PMID- 17526306
TI  - 'It hurts so much, I can't walk!' Arterial ulcers--etiology and assessment.

PMID- 17526307
TI  - Back to the basics.

PMID- 17526308
TI  - Living with lichen planopilaris.

PMID- 17526309
TI  - Alopecia areata.

PMID- 17526310
TI  - Chromoblastomycosis.

PMID- 17526311
TI  - Connective tissue disorders.

PMID- 17526312
TI  - When global is local: the culturally competent organization.

PMID- 17526313
TI  - The impact of diversity in schools of nursing: health research and health policy.

PMID- 17526314
TI  - Culturally competent staff: stories and learnings from Children's National
      Medical Center, Washington, D.C.

PMID- 17526315
TI  - Health care providers as cultural brokers: paying attention to the first
      interaction.

PMID- 17526316
TI  - Every clinical encounter is a cultural encounter: understanding the patient's
      story.

PMID- 17526317
TI  - New IUHPE research report series gives graduate students a new avenue to
      disseminate their research globally.

PMID- 17526318
TI  - Identifying and strengthening the structural roots of urban health in Canada:
      participatory policy research and the urban health agenda.
AB  - An urban health research agenda for health promoters is presented. In Canada,
      urban issues are emerging as a major concern of policy makers. The voices raising
      these issues are from the non-health sectors, but many of these issues such as
      increasing income inequality and poverty, homelessness and housing insecurity,
      and social exclusion of youth, immigrants, and ethno-racial minorities have
      strong health implications as they are important social determinants of health.
      Emphasis on these and other social determinants of health and the policy
      decisions that strengthen or weaken them is timely as the quality of Canadian
      urban environments has become especially problematic. We argue for a
      participatory urban health research and action agenda with four components: (a)
      an emphasis on health promotion and the social determinants of health; (b)
      community-based participatory research; and (c) drawing on the lived experience
      of people to influence (d) policy analysis and policy change. Urban health
      researchers and promoters are urged to draw upon new developments in population
      health and community-based health promotion theory and research to identify and
      strengthen the roots of urban health through citizen action on public policy.

PMID- 17526319
TI  - Health-enhancing physical activity and health-related risk in a sample of north
      Mexican, office-based employees.
AB  - Levels of hypertension, obesity and raised total cholesterol are increasing in
      Mexico. Mexicans employed within sedentary occupations may be particularly at
      risk of developing one, or a clustering of these health-related risk factors, due
      to lack of participation in health enhancing physical activity (HEPA). The
      purpose of this study is to examine: (a) prevalence rates of hypertension,
      obesity and raised total cholesterol, and (b) the link between these variables
      and HEPA, in a sample of North Mexican, office-based employees. Methods include
      an assessment of systolic/diastolic blood pressure, % body fat, total cholesterol
      and HEPA (7-day self-report) in 47 men (33 +/- 10 years) and 43 women (28 +/- 7
      years) from Monterrey, a large industrial city in the Northeast of Mexico. Values
      were compared against recognised health-related thresholds to determine
      prevalence rates of individual health-related risk factors, along with clustering
      of two or more risk factors. Relationships between variables were analysed using
      Pearson product moment correlation. The results show Men had a high prevalence of
      obesity (32%) and raised total cholesterol (44%), while women's rates were lower
      (7% and 10% respectively). More men (59%) than women (17%) demonstrated a
      clustering of two or more risk factors. HEPA participation was low in both men
      (9%) and women (16%). A significant relationship was found between men's HEPA and
      % body fat (r = -0.31; p < 0.05). CONCLUSIONS: The high levels of inactivity
      found in both men and women were cause for concern, suggesting the need for
      innovative intervention approaches, which aim to integrate physical activity into
      busy working lives.

PMID- 17526320
TI  - The Heartfile Lodhran CVD prevention project--end of project evaluation.
AB  - Mainstream preventive interventions often fail to reach poor populations with a
      high risk of cardiovascular diseases (CVDs) in Pakistan. A community-based CVD
      primary prevention project aimed at developing approaches to reduce risk factors
      in such populations was established by Heartfile in collaboration with the
      National Rural Support Program in the district of Lodhran. The project
      implemented a range of activities integrated with existing social and health
      service mechanisms during a three year intervention period 2000/01-03/04. These
      were targeted in 4 key settings: community health education, mass media
      interventions, training of health professionals and health education through Lady
      Health Workers. The project received support from the Department for
      International Development, U.K. At the community level, a pre-test-post-test
      quasi-experimental design was used for examining project outcomes related to the
      community component of the intervention. Pre and post-intervention (training)
      evaluations were conducted involving all health care providers in randomly
      selected workshops in order to determine baseline levels of knowledge and the
      impact of training on knowledge level. In order to assess practices of physician
      and non-physician health care providers patient interviews, with control
      comparisons were conducted at each health care facility. Significant positive
      changes were observed in knowledge levels at a community level in the district of
      intervention compared with baseline knowledge levels particularly in relation to
      a heart healthy diet, beneficial level of physical activity, the causes of high
      blood pressure and heart attack and the effects of high blood pressure and active
      and passive smoking on health. Significant changes in behaviors at a practice
      level were not shown in the district of intervention. However the project played
      a critical role in spurring national action for the prevention and control of non
      communicable diseases and introducing sustainable public health interventions for
      poor communities in Pakistan.

PMID- 17526321
TI  - A role for workforce competencies in evidence-based health promotion education.
AB  - Education programs should be based on research about the knowledge and skills
      required for practice, rather than on intuition or tradition, but there is
      limited published curriculum research on health promotion education. This paper
      describes a case study of how workforce competencies have been used to assist
      evidence-based health promotion education in the areas of curriculum design,
      selection of assessment tasks and continuous quality assurance processes in an
      undergraduate program at an Australian university. A curriculum-competency
      mapping process successfully identified gaps and areas of overlap in an existing
      program. Previously published health promotion workforce competencies were
      effectively used in the process of selecting assessment items, providing clear
      guidelines for curriculum revision and a useful method to objectively assess
      competency content in an evidence informed framework. These health promotion
      workforce competencies constituted an additional tool to assess course quality.
      We recommend other tertiary institutions consider curriculum-competency mapping
      and curriculum based assessment selection as quality and evidence based
      curriculum review strategies.

PMID- 17526322
TI  - Knowledge synthesis, translation and exchange in public health and health
      promotion: the role of a Cochrane Review Group.
AB  - The Cochrane Collaboration is an international non-profit organisation that aims
      to produce high quality systematic reviews of the effectiveness of health
      interventions. This work is conducted by 51 Review Groups that span a range of
      topics (e.g. pregnancy and childbirth, HIV/AIDS). The role of Fields within the
      Collaboration has been to actively engage relevant stakeholders internationally
      to improve the quality and relevance of reviews. Since the inception in 1996 of
      the Cochrane Public Health and Health Promotion Field, the Cochrane Collaboration
      has begun to embrace reviews related to public health and health promotion and is
      adapting to the changing needs of end-users. The introduction of a Cochrane
      health promotion and public health review group will help ensure that reviews
      will be oriented towards building evidence for equity and reducing inequalities
      and best meet the needs of decision-makers, practitioners and consumers. Our role
      as a Field has led to us working with a range of partners including reviewers,
      researchers, practitioners and consumers. Knowledge synthesis, translation and
      exchange (KST&E) has emerged as an issue in need of further exploration for
      practice to influence decision-makers and for policy to influence practitioners.
      2007 will be an exciting year for evidence-informed Health Promotion and Public
      Health (HPPH) both within the Cochrane Collaboration and for our partners in
      policy, practice and research.

PMID- 17526323
TI  - Adolescent peers and anti-smoking activities.
AB  - In this paper, we aim to evaluate and discuss the details of a five days' peer
      education training program, including creative drama techniques, which was then
      used to carry out anti-smoking activities among a group of 10th grade adolescents
      at a high school in Ankara, Turkey. Participatory methods/approaches were used
      during the training of the peers. Interactive (ice-breakers, feedback of the
      peers about each day of the training, role play, brain storming discussions, case
      studies, video recording, etc) and creative drama techniques were the two major
      training methods used during the process. Although the smoking prevalence in the
      study school did not significantly decrease after the intervention, this method
      contributed to increasing students' awareness of anti-smoking issues. Change in
      the knowledge and attitudes of the students in the study school were
      significantly different from the change in the control school. This study was
      also an opportunity for the peer leaders to be part of an enjoyable educational
      activity. The findings of the study suggest that peer counselors, well trained,
      and with on-going supervision, can have a positive effect on "knowledge" and
      "attitudes" about smoking among their friends. Changing behaviors may require a
      longer time. Peer counseling programs in which the intervention component lasts
      at least 6 months are recommended to be carried out among similar groups.

PMID- 17526324
TI  - [Health literacy and health education: what do these terms mean in the
      francophone context?].
AB  - The objective of this exploratory study is to describe the nature of the
      definitions of health literacy and health education with the intention of
      contributing to the development of common semantics to enable professionals to
      exchange knowledge with less confusion. The methodology consisted of conducting a
      literature review of francophone databases using the following key words:
      literacy and education combined with the word health. The second phase of this
      research involved reading 126 articles found in francophone databases and
      collected from the Internet. The third included reading 14 documents focused on
      the relationship between literacy/education and health with the aim of defining
      each word and identifying their characteristics. The results show that
      francophone authors from North America used both terms, health literacy and
      health education, interchangeably; while European authors only refer to health
      education. Nonetheless, the analysis revealed that both terms have the same
      meaning on either side of the Atlantic, given that the nature of their
      definitions and their expected outcomes are the same. In conclusion, this study
      suggests that there is a need for an in-depth theoretical debate on these
      concepts in the francophone world and for stronger consideration of health
      literacy specifically targeting the community level, rather than the individual.

PMID- 17526325
TI  - Exercises for mental wellness. Couldn't we all benefit?
AB  - For most of us, our cognitive functioning could be improved in many ways. Many of
      us struggle with our thinking skills at times, especially during times of stress
      and information overload. Some of the research that supports the use of
      prescribed cognitive exercises to slow cognitive decline in older adults may
      ultimately prove to be beneficial for all of us. Mental health nurses should
      encourage regular daily mental workouts, along with aerobic physical exercises,
      for everyone, not just older adults. Personal fitness training should focus not
      only on physical fitness, but also on mental fitness.

PMID- 17526326
TI  - Paliperidone extended-release tablets: a new atypical antipsychotic.
AB  - This article reviews the use of the new atypical antipsychotic drug paliperidone
      extended-release (Pal-ER). Pal-ER is a delayed-release formulation that provides
      continual drug delivery over 24 hours and reduces fluctuations in serum drug
      concentrations. This delayed release minimizes side effects related to high serum
      levels that occur with immediate-release formulations. Pal-ER is effective, safe,
      and relatively well tolerated. Although Pal-ER does not have any major advantages
      or disadvantages compared with other antipsychotic drugs, it has unique
      pharmacological properties and may be a beneficial alternative medication for
      some patients.

PMID- 17526327
TI  - Who will care for the grandparents? Exploring relationships between grandparents
      and grandchildren.
AB  - Adult children are often identified as primary caregivers for their older adult
      parents; however, in a growing number of cases, the adult child does not become
      the caregiver. Evidence of this includes the growing social phenomenon of
      grandparents raising their grandchildren. In this qualitative research project,
      the long-term caregiving relationship between grandparents and grandchildren
      living in grandparent-headed households was explored through interviews with
      three grandparent-grandchild dyads. The ongoing relationship in the dyads did not
      seem to mimic a parent-child relationship or a grandparent-grandchild
      relationship, but instead a third kind of relationship that requires further
      exploration.

PMID- 17526328
TI  - Providing psychiatric-mental health care for Native Americans: lessons learned by
      a non-Native American PMHNP.
AB  - Providing culturally sensitive psychiatric-mental health nursing care to Native
      Americans requires a unique set of understandings. Traditional tribal customs and
      beliefs, historical events of the past 500 years, and acculturation and
      enculturation have affected Native Americans' health and well-being. In 2004, I
      had the opportunity to practice as a psychiatric-mental health nurse practitioner
      with a Native American tribe in the southwestern United States. This article
      describes the lessons I learned while practicing on the reservation and suggests
      ways other non-Native American practitioners can best serve this population.

PMID- 17526329
TI  - Competencies and roles of community mental health nurses.
AB  - Community mental health nurses practice in a range of behavioral health care
      settings, including community mental health centers, detoxification centers,
      group homes for individuals with mental retardation or serious mental illnesses,
      and residential substance abuse treatment programs. As the population for whom
      they care grows and ages and with an increase in comorbid conditions, different
      skills may be needed or different roles may require emphasis. This can present
      challenges related to role competencies and nursing preparation and to the
      allocation of their time. The overall purposes of this project were to compare
      the competencies of basic and advanced practice nurses with accepted psychiatric
      mental health nursing competencies and to assess the nurses' roles and division
      of work time among various roles. The findings support the need for changes
      related to nursing roles and job descriptions. Specific recommendations have been
      implemented based on the findings.

PMID- 17526330
TI  - Staff resistance to restraint reduction: identifying & overcoming barriers.
AB  - Professional organizations, regulating agencies, and hospital administrators have
      taken a strong stance on restraint reduction policies. When implementing a
      restraint reduction initiative, it is important to identify the barriers to
      restraint reduction, such as concern for personal safety, lack of knowledge about
      and practice using alternate de-escalation skills, and fear of disrupting the
      therapeutic milieu by using a variety of de-escalation methods. Education aimed
      to reduce the use of restraints needs to do more than simply provide information.
      It is important to acknowledge the emotional response of the nursing staff and
      the culture of the current practice. A variety of educational strategies,
      including role-playing, and case studies will help identify attitudes, beliefs,
      and behaviors that are congruent with reducing the use of restraints. If the
      ultimate goal of restraint reduction is philosophical change, it will eventually
      lead to a new culture of practice.

PMID- 17526331
TI  - Deterministic learning and rapid dynamical pattern recognition.
AB  - Recognition of temporal/dynamical patterns is among the most difficult pattern
      recognition tasks. In this paper, based on a recent result on deterministic
      learning theory, a deterministic framework is proposed for rapid recognition of
      dynamical patterns. First, it is shown that a time-varying dynamical pattern can
      be effectively represented in a time-invariant and spatially distributed manner
      through deterministic learning. Second, a definition for characterizing
      similarity of dynamical patterns is given based on system dynamics inherently
      within dynamical patterns. Third, a mechanism for rapid recognition of dynamical
      patterns is presented, by which a test dynamical pattern is recognized as similar
      to a training dynamical pattern if state synchronization is achieved according to
      a kind of internal and dynamical matching on system dynamics. The synchronization
      errors can be taken as the measure of similarity between the test and training
      patterns. The significance of the paper is that a completely dynamical approach
      is proposed, in which the problem of dynamical pattern recognition is turned into
      the stability and convergence of a recognition error system. Simulation studies
      are included to demonstrate the effectiveness of the proposed approach.

PMID- 17526332
TI  - Continuous-time adaptive critics.
AB  - A continuous-time formulation of an adaptive critic design (ACD) is investigated.
      Connections to the discrete case are made, where backpropagation through time
      (BPTT) and real-time recurrent learning (RTRL) are prevalent. Practical benefits
      are that this framework fits in well with plant descriptions given by
      differential equations and that any standard integration routine with adaptive
      step-size does an adaptive sampling for free. A second-order actor adaptation
      using Newton's method is established for fast actor convergence for a general
      plant and critic. Also, a fast critic update for concurrent actor-critic training
      is introduced to immediately apply necessary adjustments of critic parameters
      induced by actor updates to keep the Bellman optimality correct to first-order
      approximation after actor changes. Thus, critic and actor updates may be
      performed at the same time until some substantial error build up in the Bellman
      optimality or temporal difference equation, when a traditional critic training
      needs to be performed and then another interval of concurrent actor-critic
      training may resume.

PMID- 17526333
TI  - Sparse distributed memory using rank-order neural codes.
AB  - A variant of a sparse distributed memory (SDM) is shown to have the capability of
      storing and recalling patterns containing rank-order information. These are
      patterns where information is encoded not only in the subset of neuron outputs
      that fire, but also in the order in which that subset fires. This is an
      interesting companion to several recent works in the neuroscience literature,
      showing that human memories may be stored in terms of neural spike timings. In
      our model, the ordering is stored in static synaptic weights using a Hebbian
      single-shot learning algorithm, and can be reliably recovered whenever the
      associated input is supplied. It is shown that the memory can operate using only
      unipolar binary connections throughout. The behavior of the memory under noisy
      input conditions is also investigated. It is shown that the memory is capable of
      improving the quality of the data that passes through it. That is, under
      appropriate conditions the output retrieved from the memory is less noisy than
      the input used to retrieve it. Thus, this memory architecture could be used as a
      component in a complex system with stable noise properties and, we argue, it can
      be implemented using spiking neurons.

PMID- 17526334
TI  - Stability analysis and the stabilization of a class of discrete-time dynamic
      neural networks.
AB  - This paper deals with problems of stability and the stabilization of discrete
      time neural networks. Neural structures under consideration belong to the class
      of the so-called locally recurrent globally feedforward networks. The single
      processing unit possesses dynamic behavior. It is realized by introducing into
      the neuron structure a linear dynamic system in the form of an infinite impulse
      response filter. In this way, a dynamic neural network is obtained. It is well
      known that the crucial problem with neural networks of the dynamic type is
      stability as well as stabilization in learning problems. The paper formulates
      stability conditions for the analyzed class of neural networks. Moreover, a
      stabilization problem is defined and solved as a constrained optimization task.
      In order to tackle this problem two methods are proposed. The first one is based
      on a gradient projection (GP) and the second one on a minimum distance projection
      (MDP). It is worth noting that these methods can be easily introduced into the
      existing learning algorithm as an additional step, and suitable convergence
      conditions can be developed for them. The efficiency and usefulness of the
      proposed approaches are justified by using a number of experiments including
      numerical complexity analysis, stabilization effectiveness, and the
      identification of an industrial process.

PMID- 17526335
TI  - Training winner-take-all simultaneous recurrent neural networks.
AB  - The winner-take-all (WTA) network is useful in database management, very large
      scale integration (VLSI) design, and digital processing. The synthesis procedure
      of WTA on single-layer fully connected architecture with sigmoid transfer
      function is still not fully explored. We discuss the use of simultaneous
      recurrent networks (SRNs) trained by Kalman filter algorithms for the task of
      finding the maximum among N numbers. The simulation demonstrates the
      effectiveness of our training approach under conditions of a shared-weight SRN
      architecture. A more general SRN also succeeds in solving a real classification
      application on car engine data.

PMID- 17526336
TI  - Fast sparse approximation for least squares support vector machine.
AB  - In this paper, we present two fast sparse approximation schemes for least squares
      support vector machine (LS-SVM), named FSALS-SVM and PFSALS-SVM, to overcome the
      limitation of LS-SVM that it is not applicable to large data sets and to improve
      test speed. FSALS-SVM iteratively builds the decision function by adding one
      basis function from a kernel-based dictionary at one time. The process is
      terminated by using a flexible and stable epsilon insensitive stopping criterion.
      A probabilistic speedup scheme is employed to further improve the speed of FSALS
      SVM and the resulting classifier is named PFSALS-SVM. Our algorithms are of two
      compelling features: low complexity and sparse solution. Experiments on benchmark
      data sets show that our algorithms obtain sparse classifiers at a rather low cost
      without sacrificing the generalization performance.

PMID- 17526337
TI  - Boolean factor analysis by attractor neural network.
AB  - A common problem encountered in disciplines such as statistics, data analysis,
      signal processing, textual data representation, and neural network research, is
      finding a suitable representation of the data in the lower dimension space. One
      of the principles used for this reason is a factor analysis. In this paper, we
      show that Hebbian learning and a Hopfield-like neural network could be used for a
      natural procedure for Boolean factor analysis. To ensure efficient Boolean factor
      analysis, we propose our original modification not only of Hopfield network
      architecture but also its dynamics as well. In this paper, we describe neural
      network implementation of the Boolean factor analysis method. We show the
      advantages of our Hopfield-like network modification step by step on artificially
      generated data. At the end, we show the efficiency of the method on artificial
      data containing a known list of factors. Our approach has the advantage of being
      able to analyze very large data sets while preserving the nature of the data.

PMID- 17526338
TI  - RCMAC hybrid control for MIMO uncertain nonlinear systems using sliding-mode
      technology.
AB  - A hybrid control system, integrating principal and compensation controllers, is
      developed for multiple-input-multiple-output (MIMO) uncertain nonlinear systems.
      This hybrid control system is based on sliding-mode technique and uses a
      recurrent cerebellar model articulation controller (RCMAC) as an uncertainty
      observer. The principal controller containing an RCMAC uncertainty observer is
      the main controller, and the compensation controller is a compensator for the
      approximation error of the system uncertainty. In addition, in order to relax the
      requirement of approximation error bound, an estimation law is derived to
      estimate the error bound. The Taylor linearization technique is employed to
      increase the learning ability of RCMAC and the adaptive laws of the control
      system are derived based on Lyapunov stability theorem and Barbalat's lemma so
      that the asymptotical stability of the system can be guaranteed. Finally, the
      proposed design method is applied to control a biped robot. Simulation results
      demonstrate the effectiveness of the proposed control scheme for the MIMO
      uncertain nonlinear system.

PMID- 17526339
TI  - An approach to estimating product design time based on fuzzy v-support vector
      machine.
AB  - This paper presents a new version of fuzzy support vector machine (FSVM)
      developed for product design time estimation. As there exist problems of finite
      samples and uncertain data in the estimation, the input and output variables are
      described as fuzzy numbers, with the metric on fuzzy number space defined. Then,
      the fuzzy v-support vector machine (Fv-SVM) is proposed on the basis of combining
      the fuzzy theory with the v-support vector machine, followed by the presentation
      of a time estimation method based on Fv-SVM and its relevant parameter-choosing
      algorithm. The results from the applications in injection mold design and
      software product design confirm the feasibility and validity of the estimation
      method. Compared with the fuzzy neural network (FNN) model, our Fv-SVM method
      requires fewer samples and enjoys higher estimating precision.

PMID- 17526340
TI  - Simultaneous pattern classification and multidomain association using self
      structuring kernel memory networks.
AB  - In this paper, a novel exemplar-based constructive approach using kernels is
      proposed for simultaneous pattern classification and multidomain pattern
      association tasks. The kernel networks are constructed on a modular basis by a
      simple one-shot self-structuring algorithm motivated from the traditional Hebbian
      principle and then, they act as the flexible memory capable of generalization for
      the respective classes. In the self-structuring kernel memory (SSKM), any arduous
      and iterative network parameter tuning is not involved for establishing the
      weight connections during the construction, unlike conventional approaches, and
      thereby, it is considered that the networks do not inherently suffer from the
      associated numerical instability. Then, the approach is extended for multidomain
      pattern association, in which a particular domain input cannot only activate some
      kernel units (KUs) but also the kernels in other domain(s) via the cross-domain
      connection(s) in between. Thereby, the SSKM can be regarded as a simultaneous
      pattern classifier and associator. In the simulation study for pattern
      classification, it is justified that an SSKM consisting of distinct kernel
      networks can yield relatively compact-sized pattern classifiers, while preserving
      a reasonably high generalization capability, in comparison with the approach
      using support vector machines (SVMs).

PMID- 17526341
TI  - Unsupervised learning of gaussian mixtures based on variational component
      splitting.
AB  - In this paper, we present an incremental method for model selection and learning
      of Gaussian mixtures based on the recently proposed variational Bayes approach.
      The method adds components to the mixture using a Bayesian splitting test
      procedure: a component is split into two components and then variational update
      equations are applied only to the parameters of the two components. As a result,
      either both components are retained in the model or one of them is found to be
      redundant and is eliminated from the model. In our approach, the model selection
      problem is treated locally, in a region of the data space, so we can set more
      informative priors based on the local data distribution. A modified Bayesian
      mixture model is presented to implement this approach, along with a learning
      algorithm that iteratively applies a splitting test on each mixture component.
      Experimental results and comparisons with two other techniques testify for the
      adequacy of the proposed approach.

PMID- 17526342
TI  - A weighted voting model of associative memory.
AB  - This paper presents an analysis of a random access memory (RAM)-based associative
      memory which uses a weighted voting scheme for information retrieval. This
      weighted voting memory can operate in heteroassociative or autoassociative mode,
      can store both real-valued and binary-valued patterns and, unlike memory models,
      is equipped with a rejection mechanism. A theoretical analysis of the performance
      of the weighted voting memory is given for the case of binary and random memory
      sets. Performance measures are derived as a function of the model parameters:
      pattern size, window size, and number of patterns in the memory set. It is shown
      that the weighted voting model has large capacity and error correction. The
      results show that the weighted voting model can successfully achieve high
      detection and -identification rates and, simultaneously, low-false-acceptance
      rates.

PMID- 17526343
TI  - A class of single-class minimax probability machines for novelty detection.
AB  - Single-class minimax probability machines (MPMs) offer robust novelty detection
      with distribution-free worst case bounds on the probability that a pattern will
      fall inside the normal region. However, in practice, they are too cautious in
      labeling patterns as outlying and so have a high false negative rate (FNR). In
      this paper, we propose a more aggressive version of the single-class MPM that
      bounds the best case probability that a pattern will fall inside the normal
      region. These two MPMs can then be used together to delimit the solution space.
      By using the hyperplane lying in the middle of this pair of MPMs, a better
      compromise between false positives (FPs) and false negatives (FNs), and between
      recall and precision can be obtained. Experiments on the real-world data sets
      show encouraging results.

PMID- 17526344
TI  - Explicit magnification control of self-organizing maps for "forbidden" data.
AB  - In this paper, we examine the scope of validity of the explicit self-organizing
      map (SOM) magnification control scheme of Bauer et al. (1996) on data for which
      the theory does not guarantee success, namely data that are n-dimensional, n > or
      =2, and whose components in the different dimensions are not statistically
      independent. The Bauer et al. algorithm is very attractive for the possibility of
      faithful representation of the probability density function (pdf) of a data
      manifold, or for discovery of rare events, among other properties. Since
      theoretically unsupported data of higher dimensionality and higher complexity
      would benefit most from the power of explicit magnification control, we conduct
      systematic simulations on "forbidden" data. For the unsupported n=2 cases that we
      investigate, the simulations show that even though the magnification exponent
      alpha achieved achieved by magnification control is not the same as the desired
      alpha desired, alpha achieved systematically follows alpha desired with a slowly
      increasing positive offset. We show that for simple synthetic higher dimensional
      data information, theoretically optimum pdf matching (alpha achieved = 1) can be
      achieved, and that negative magnification has the desired effect of improving the
      detectability of rare classes. In addition, we further study theoretically
      unsupported cases with real data.

PMID- 17526345
TI  - A spatially constrained generative model and an EM algorithm for image
      segmentation.
AB  - In this paper, we present a novel spatially constrained generative model and an
      expectation-maximization (EM) algorithm for model-based image segmentation. The
      generative model assumes that the unobserved class labels of neighboring pixels
      in the image are generated by prior distributions with similar parameters, where
      similarity is defined by entropic quantities relating to the neighboring priors.
      In order to estimate model parameters from observations, we derive a spatially
      constrained EM algorithm that iteratively maximizes a lower bound on the data log
      likelihood, where the penalty term is data-dependent. Our algorithm is very easy
      to implement and is similar to the standard EM algorithm for Gaussian mixtures
      with the main difference that the labels posteriors are "smoothed" over pixels
      between each E- and M-step by a standard image filter. Experiments on synthetic
      and real images show that our algorithm achieves competitive segmentation results
      compared to other Markov-based methods, and is in general faster.

PMID- 17526346
TI  - A minimum-range approach to blind extraction of bounded sources.
AB  - In spite of the numerous approaches that have been derived for solving the
      independent component analysis (ICA) problem, it is still interesting to develop
      new methods when, among other reasons, specific a priori knowledge may help to
      further improve the separation performances. In this paper, the minimum-range
      approach to blind extraction of bounded source is investigated. The relationship
      with other existing well-known criteria is established. It is proved that the
      minimum-range approach is a contrast, and that the criterion is discriminant in
      the sense that it is free of spurious maxima. The practical issues are also
      discussed, and a range measure estimation is proposed based on the order
      statistics. An algorithm for contrast maximization over the group of special
      orthogonal matrices is proposed. Simulation results illustrate the performances
      of the algorithm when using the proposed range estimation criterion.

PMID- 17526347
TI  - Higher-order-statistics-based radial basis function networks for signal
      enhancement.
AB  - In this paper, a higher-order-statistics (HOS)-based radial basis function (RBF)
      network for signal enhancement is introduced. In the proposed scheme, higher
      order cumulants of the reference signal were used as the input of HOS-based RBF.
      An HOS-based supervised learning algorithm, with mean square error obtained from
      higher order cumulants of the desired input and the system output as the learning
      criterion, was used to adapt weights. The motivation is that the HOS can
      effectively suppress Gaussian and symmetrically distributed non-Gaussian noise.
      The influence of a Gaussian noise on the input of HOS-based RBF and the HOS-based
      learning algorithm can be mitigated. Simulated results indicate that HOS-based
      RBF can provide better performance for signal enhancement under different noise
      levels, and its performance is insensitive to the selection of learning rates.
      Moreover, the efficiency of HOS-based RBF under the nonstationary Gaussian noise
      is stable.

PMID- 17526348
TI  - Hierarchical singleton-type recurrent neural fuzzy networks for noisy speech
      recognition.
AB  - This paper proposes noisy speech recognition using hierarchical singleton-type
      recurrent neural fuzzy networks (HSRNFNs). The proposed HSRNFN is a hierarchical
      connection of two singleton-type recurrent neural fuzzy networks (SRNFNs), where
      one is used for noise filtering and the other for recognition. The SRNFN is
      constructed by recurrent fuzzy if-then rules with fuzzy singletons in the
      consequences, and their recurrent properties make them suitable for processing
      speech patterns with temporal characteristics. In n words recognition, n SRNFNs
      are created for modeling n words, where each SRNFN receives the current frame
      feature and predicts the next one of its modeling word. The prediction error of
      each SRNFN is used as recognition criterion. In filtering, one SRNFN is created,
      and each SRNFN recognizer is connected to the same SRNFN filter, which filters
      noisy speech patterns in the feature domain before feeding them to the SRNFN
      recognizer. Experiments with Mandarin word recognition under different types of
      noise are performed. Other recognizers, including multilayer perceptron (MLP),
      time-delay neural networks (TDNNs), and hidden Markov models (HMMs), are also
      tested and compared. These experiments and comparisons demonstrate good results
      with HSRNFN for noisy speech recognition tasks.

PMID- 17526349
TI  - Iterative least squares functional networks classifier.
AB  - This paper proposes unconstrained functional networks as a new classifier to deal
      with the pattern recognition problems. Both methodology and learning algorithm
      for this kind of computational intelligence classifier using the iterative least
      squares optimization criterion are derived. The performance of this new
      intelligent systems scheme is demonstrated and examined using real-world
      applications. A comparative study with the most common classification algorithms
      in both machine learning and statistics communities is carried out. The study was
      achieved with only sets of second-order linearly independent polynomial functions
      to approximate the neuron functions. The results show that this new framework
      classifier is reliable, flexible, stable, and achieves a high-quality
      performance.

PMID- 17526350
TI  - A hybrid neurogenetic approach for stock forecasting.
AB  - In this paper, we propose a hybrid neurogenetic system for stock trading. A
      recurrent neural network (NN) having one hidden layer is used for the prediction
      model. The input features are generated from a number of technical indicators
      being used by financial experts. The genetic algorithm (GA) optimizes the NN's
      weights under a 2-D encoding and crossover. We devised a context-based ensemble
      method of NNs which dynamically changes on the basis of the test day's context.
      To reduce the time in processing mass data, we parallelized the GA on a Linux
      cluster system using message passing interface. We tested the proposed method
      with 36 companies in NYSE and NASDAQ for 13 years from 1992 to 2004. The
      neurogenetic hybrid showed notable improvement on the average over the buy-and
      hold strategy and the context-based ensemble further improved the results. We
      also observed that some companies were more predictable than others, which
      implies that the proposed neurogenetic hybrid can be used for financial portfolio
      construction.

PMID- 17526351
TI  - An improved dynamic neurocontroller based on Christoffel symbols.
AB  - In this paper, a dynamic neurocontroller for positioning of robots based on
      static and parametric neural networks (NNs) has been developed. This controller
      is based on Christoffel symbols of first kind in order to carry out
      coriolis/centripetal matrix. Structural properties of robots and Kronecker
      product has been taken into account to develop NNs to approximate nonlinearities.
      The weight updating laws have been obtained from a nonlinear strategy based on
      Lyapunov energy that guarantees both stability and boundedness of signals and
      weights. The NN weights are tuned online with no "offline learning phase" and are
      initialized to zero. The neurocontroller improves the implementation with respect
      to other dynamic NNs used in the literature.

PMID- 17526352
TI  - Feedforward neural network implementation in FPGA using layer multiplexing for
      effective resource utilization.
AB  - This paper presents a hardware implementation of multilayer feedforward neural
      networks (NN) using reconfigurable field-programmable gate arrays (FPGAs).
      Despite improvements in FPGA densities, the numerous multipliers in an NN limit
      the size of the network that can be implemented using a single FPGA, thus making
      NN applications not viable commercially. The proposed implementation is aimed at
      reducing resource requirement, without much compromise on the speed, so that a
      larger NN can be realized on a single chip at a lower cost. The sequential
      processing of the layers in an NN has been exploited in this paper to implement
      large NNs using a method of layer multiplexing. Instead of realizing a complete
      network, only the single largest layer is implemented. The same layer behaves as
      different layers with the help of a control block. The control block ensures
      proper functioning by assigning the appropriate inputs, weights, biases, and
      excitation function of the layer that is currently being computed. Multilayer
      networks have been implemented using Xilinx FPGA "XCV400hq240". The concept used
      is shown to be very effective in reducing resource requirements at the cost of a
      moderate overhead on speed. This implementation is proposed to make NN
      applications viable in terms of cost and speed for online applications. An NN
      based flux estimator is implemented in FPGA and the results obtained are
      presented.

PMID- 17526353
TI  - Real-time neural network inversion on the SRC-6e reconfigurable computer.
AB  - Implementation of real-time neural network inversion on the SRC-6e, a computer
      that uses multiple field-programmable gate arrays (FPGAs) as reconfigurable
      computing elements, is examined using a sonar application as a specific case
      study. A feedforward multilayer perceptron neural network is used to estimate the
      performance of the sonar system (Jung et al., 2001). A particle swarm algorithm
      uses the trained network to perform a search for the control parameters required
      to optimize the output performance of the sonar system in the presence of imposed
      environmental constraints (Fox et al., 2002). The particle swarm optimization
      (PSO) requires repetitive queries of the neural network. Alternatives for
      implementing neural networks and particle swarm algorithms in reconfigurable
      hardware are contrasted. The final implementation provides nearly two orders of
      magnitude of speed increase over a state-of-the-art personal computer (PC),
      providing a real-time solution.

PMID- 17526354
TI  - Performance of the Bayesian online algorithm for the perceptron.
AB  - In this letter, we derive continuum equations for the generalization error of the
      Bayesian online algorithm (BOnA) for the one-layer perceptron with a spherical
      covariance matrix using the Rosenblatt potential and show, by numerical
      calculations, that the asymptotic performance of the algorithm is the same as the
      one for the optimal algorithm found by means of variational methods with the
      added advantage that the BOnA does not use any inaccessible information during
      learning.

PMID- 17526355
TI  - Variational Bayesian approach to canonical correlation analysis.
AB  - As a dimension reduction algorithm, canonical correlation analysis (CCA)
      encounters the issue of selecting the number of canonical correlations. In this
      letter, we present a Bayesian model selection algorithm for CCA based on a
      probabilistic interpretation. A hierarchical Bayesian model is applied to
      probabilistic CCA and learned by variational approximation. This method not only
      estimates the model parameters, but also automatically determines the number of
      canonical correlations and avoids overfitting. Experiments show that it performs
      better compared with maximum likelihood and some other model selection methods.

PMID- 17526356
TI  - Determination of the number of principal directions in a biologically plausible
      PCA model.
AB  - Adaptively determining an appropriate number of principal directions for
      principal component analysis (PCA) neural networks is an important problem to
      address when one uses PCA neural networks for online feature extraction. In this
      letter, inspired from biological neural networks, a single-layer neural network
      model with lateral connections is proposed which uses an improved generalized
      Hebbian algorithm (GHA) to address this problem. In the proposed model, the
      number of principal directions can be adaptively determined to approximate the
      intrinsic dimensionality of the given data set so that the dimensionality of the
      data set can be reduced to approach the intrinsic dimensionality to any required
      precision through the network.

PMID- 17526357
TI  - A convex approach to validation-based learning of the regularization constant.
AB  - This letter investigates a tight convex relaxation to the problem of tuning the
      regularization constant with respect to a validation based criterion. A number of
      algorithms is covered including ridge regression, regularization networks,
      smoothing splines, and least squares support vector machines (LS-SVMs) for
      regression. This convex approach allows the application of reliable and efficient
      tools, thereby improving computational cost and automatization of the learning
      method. It is shown that all solutions of the relaxation allow an interpretation
      in terms of a solution to a weighted LS-SVM.

PMID- 17526358
TI  - Neural-network-based nonlinear adaptive dynamical decoupling control.
AB  - In this letter, a nonlinear adaptive dynamical decoupling control algorithm using
      neural networks (NNs), a novel technique, is proposed for a class of uncertain
      nonlinear multivariable discrete-time dynamical systems. By combining open-loop
      decoupling compensation and generalized minimum variance adaptive scheme with
      NNs, complete dynamical decoupling is realized. The algorithm is applicable to
      the systems which are open-loop unstable and nonminimum phase in a neighborhood
      of the origin [symbol: see text]. In the domain [symbol: see text], it can assure
      the bounded-input-bounded-output (BIBO) stability of the closed-loop system and
      can also make the generalized tracking error converge to a neighborhood of zero,
      whose size is evaluated and depends on the approximation error of the NN. Theory
      analysis and simulation results are presented to show the effectiveness of the
      proposed method.

PMID- 17526359
TI  - Knowledge extraction from neural networks using the all-permutations fuzzy rule
      base: the LED display recognition problem.
AB  - A major drawback of artificial neural networks (ANNs) is their black-box
      character. Even when the trained network performs adequately, it is very
      difficult to understand its operation. In this letter, we use the mathematical
      equivalence between ANNs and a specific fuzzy rule base to extract the knowledge
      embedded in the network. We demonstrate this using a benchmark problem: the
      recognition of digits produced by a light emitting diode (LED) device. The method
      provides a symbolic and comprehensible description of the knowledge learned by
      the network during its training.

PMID- 17526360
TI  - Blind image deconvolution through support vector regression.
AB  - This letter introduces a new algorithm for the restoration of a noisy blurred
      image based on the support vector regression (SVR). Experiments show that the
      performance of the SVR is very robust in blind image deconvolution where the
      types of blurs, point spread function (PSF) support, and noise level are all
      unknown.

PMID- 17526361
TI  - An empirical evaluation of the fuzzy kernel perceptron.
AB  - J.-H. Chen and C.-S. Chen have recently proposed a nonlinear variant of Keller
      and Hunt's fuzzy perceptron algorithm, based on the now familiar "kernel trick."
      In this letter, we demonstrate experimentally that J.-H. Chen and C.-S. Chen's
      assertion that the fuzzy kernel perceptron (FKP) outperforms the support vector
      machine (SVM) cannot be sustained. A more thorough model comparison exercise,
      based on a much wider range of benchmark data sets, shows that the FKP algorithm
      is not competitive with the SVM.

PMID- 17526362
TI  - Neural network learning with global heuristic search.
AB  - A novel hybrid global optimization (GO) algorithm applied for feedforward neural
      networks (NNs) supervised learning is investigated. The network weights are
      determined by minimizing the traditional mean square error function. The
      optimization technique, called LP(tau)NM, combines a novel global heuristic
      search based on LPtau low-discrepancy sequences of points, and a simplex local
      search. The proposed method is initially tested on multimodal mathematical
      functions and subsequently applied for training moderate size NNs for solving
      popular benchmark problems. Finally, the results are analyzed, discussed, and
      compared with such as from backpropagation (BP) (Levenberg-Marquardt) and
      differential evolution methods.

PMID- 17526363
TI  - A geometrical method to improve performance of the support vector machine.
AB  - The performance of a support vector machine (SVM) largely depends on the kernel
      function used. This letter investigates a geometrical method to optimize the
      kernel function. The method is a modification of the one proposed by S. Amari and
      S. Wu. Its concern is the use of the prior knowledge obtained in a primary step
      training to conformally rescale the kernel function, so that the separation
      between the two classes of data is enlarged. The result is that the new algorithm
      works efficiently and overcomes the susceptibility of the original method.

PMID- 17526364
TI  - Global asymptotic stability of delayed cellular neural networks.
AB  - A new criterion for the global asymptotic stability of the equilibrium point of
      cellular neural networks with multiple time delays is presented. The obtained
      result possesses the structure of a linear matrix inequality and can be solved
      efficiently using the recently developed interior-point algorithm. A numerical
      example is used to show the effectiveness of the obtained result.

PMID- 17526365
TI  - Packet loss rate prediction using the sparse basis prediction model.
AB  - The quality of multimedia communicated through the Internet is highly sensitive
      to packet loss. In this letter, we develop a time-series prediction model for the
      end-to-end packet loss rate (PLR). The estimate of the PLR is needed in several
      transmission control mechanisms such as the TCP-friendly congestion control
      mechanism for UDP traffic. In addition, it is needed to estimate the amount of
      redundancy for the forward error correction (FEC) mechanism. An accurate
      prediction would therefore be very valuable. We used a relatively novel
      prediction model called sparse basis prediction model. It is an adaptive
      nonlinear prediction approach, whereby a very large dictionary of possible inputs
      are extracted from the time series (for example, through moving averages, some
      nonlinear transformations, etc.). Only few of the very best inputs among the
      dictionary are selected and are combined linearly. An algorithm adaptively
      updates the input selection (as well as updates the weights) each time a new time
      sample arrives in a computationally efficient way. Simulation experiments
      indicate significantly better prediction performance for the sparse basis
      approach, as compared to other traditional nonlinear approaches.

PMID- 17526366
TI  - Gabor-like image filtering using a neural microcircuit.
AB  - In this letter, we present an implementation of a neural microcircuit for image
      processing employing Hebbian-adaptive learning. The neuronal circuit utilizes
      only excitatory synapses to correlate action potentials, extracting the
      uncorrelated ones, which contain significant image information. This circuit is
      capable of approximating Gabor-like image filtering and other image processing
      functions.

PMID- 17526367
TI  - Comparing support vector machines and feedforward neural networks with similar
      hidden-layer weights.
AB  - Support vector machines (SVMs) usually need a large number of support vectors to
      form their output Recently, several models have been proposed to build SVMs with
      a small number of basis functions, maintaining the property that their hidden
      layer weights are a subset of the data (the support vectors). This property is
      also present in some algorithms for feedforward neural networks (FNNs) that
      construct the network sequentially, leading to sparse models where the number of
      hidden units can be explicitly controlled. An experimental study on several
      benchmark data sets, comparing SVMs and the aforementioned sequential FNNs, was
      carried out. The experiments were performed in the same conditions for all the
      models, and they can be seen as a comparison of SVMs and FNNs when both models
      are restricted to use similar hidden-layer weights. Accuracies were found to be
      very similar. Regarding the number of support vectors, sequential FNNs
      constructed models with less hidden units than standard SVMs and in the same
      range as "sparse" SVMs. Computational times were lower for SVMs.

PMID- 17526368
TI  - Francis D. Moore.

PMID- 17526369
TI  - [Intra-uterine growth retardation and growth hormones].

PMID- 17526370
TI  - [Autoimmune thyroid disease in children].
AB  - Autoimmune thyroid disease in children includes Hashimoto thyroiditis and Graves'
      disease or toxic diffuse goitre. The immunological mechanisms involved in these
      diseases are closely related while the clinical picture differs because of the
      specific type of immunological response that occurs. Both conditions are
      connected together by their similar thyroid pathology, co-occurrence in family
      and within the same individual over time. A background inherited predisposition
      to autoimmunity with additional environmental and hormonal factors contributes to
      the development of the diseases. These observations help understand their key
      clinical features as well as their diagnostic and therapeutic approaches.

PMID- 17526371
TI  - [Goitre and thyroid nodules in children and adolescents].
AB  - Systematic examination of the thyroid gland allows discovering diffuse or
      multinodular goitres as well as solitary nodules. Goitre may be the only clinical
      manifestation of an underlying thyroid disease. Its evaluation should consider
      the familial history as well as nutritional and environmental factors. Thyroid
      ultrasonography is of critical importance to assess the diagnosis. Hashimoto's
      thyroiditis, colloid and endemic goitre are the most frequent causes of the
      diffuse form, particularly during puberty. Multinodular goitre and solitary
      thyroid nodule are rare in the paediatric age group: both conditions can reveal a
      malignant lesion. In this case, a total thyroidectomy should be performed. Long
      term outcome is excellent with an exception for medullary carcinoma which can be
      part of a multiple endocrine neoplasia (MEN type 2 A).

PMID- 17526372
TI  - [Severe chronic anemia and endocrine disorders in children].
AB  - Hemolytic anemias can induce various anomalies of the endocrine glands which can
      already be observed in children. Endocrine dysfunction is also found in the
      course of therapy for aplastic anemias, usually as undesirable side effects. In
      Europe, 2-9% of the population belongs to ethnic minorities at risk for
      developing hemolytic anemia. Pituitary affinity to iron deposition explains the
      high incidence of hypogonadism, puberty delay and growth retardation although
      other factors have to be considered. Growth hormone deficiency has to be ruled
      out as it can occur in a minority of subjects with thalassemia and sickle-cell
      disease (drepanocytosis). Diabetes mellitus, hypothyroidism and
      hypoparathyroidism may also develop. Follow-up includes close monitoring of
      growth and pubertal development in order to guide therapeutic interventions.

PMID- 17526373
TI  - [The diabetic child and the specifics of insulin therapy].
AB  - The incidence of diabetes type I has increased considerably in young children
      with an annual increase in Switzerland of 23,8% over the last ten years. The
      development of rapid acting and long acting analogues allowed a significant
      progress in treatment. Multiple daily insulin injections together with
      carbohydrate counting as well as continuous subcutaneous insulin infusion (CSII)
      improved the quality of life and led to an increased daily flexibility. The
      incidence of severe hypoglycaemic events has decreased at the same time metabolic
      control improved. The development of interstitial glucose measurement (online)
      coupled to the insulin pump represents a step further towards the artificial
      pancreas. The new therapeutic strategies of immunomodulation will hopefully lead
      to secondary and tertiary prevention of diabetes.

PMID- 17526374
TI  - [Diabetes type 2 in pediatrics: diagnosis and management].
AB  - Our way of life has led to a massive increase in the prevalence of obesity in
      adults and children. Therefore diabetes type 2 has also become a pediatric
      disease. Therapy consists above all of implementing modifications of life style
      such as a healthy diet and regular physical activity in order to achieve a
      decrease in body weight. If these measurements prove to be insufficient, medical
      treatments are introduced, either using metformine or insulin. The screening and
      treatment of complications (retinopathy, nephropathy) and comorbidities (arterial
      hypertension, dyslipidemia) will help to decrease mortality on the long haul.

PMID- 17526375
TI  - [Infection of a total knee prosthesis with Brucella spp].
AB  - Brucellosis, an "anthropophitic" disease of worldwide distribution can involve
      several organs and tissues but the osteoarticular disease is the most common
      complication. It can occur as sacroiliitis, bursitis, tenosynovitis or
      osteomyelitis. Prosthetic joint infection is a serious complication of total
      joint arthroplasty, with coagulase negative staphylococci and Staphylococcus
      aureus accounting for 50% of cases. Treatment of prosthetic infections remains
      complex. Prosthetic infections caused by Brucella spp are rarely described in the
      literature. We report a patient with a prosthetic joint infection due to Brucella
      spp, documented by a polymerase chain reaction. The patient has been cured after
      two-stage exchange of the prosthesis and long-term antimicrobial therapy.

PMID- 17526376
TI  - [Elderly of today and elderly of tomorrow].

PMID- 17526377
TI  - [Some ethical precautions before entering the world of nanotechnology].

PMID- 17526378
TI  - [A new veil removed from the physiologic mysteries of "HIV control" ].

PMID- 17526379
TI  - [Nicolas Sarkozy and the pedophilia].

PMID- 17526380
TI  - [The delivery of bad news].

PMID- 17526381
TI  - A population based survey of ergonomic risk factors in Connecticut: distribution
      by industry, occupation, and demographics.
AB  - BACKGROUND: Risk factors for upper-extremity musculoskeletal disorders (MSD)
      include biomechanical factors (force, repetition, posture) and psychosocial
      factors (job stress). A population-based telephone survey of workers in
      Connecticut characterized these risk factors by industry, occupation, gender, and
      age. FINDINGS: Risk factors were highly prevalent in the Connecticut workplace,
      but varied considerably by industry, occupation, gender, and age. Risk factors
      clustered based on (a) physically active occupations/industries (pushing/pulling,
      reaching, bent wrists, and tool use), (b) physically passive
      occupations/industries (static postures, stress, and computer use), and (c)
      repetitive motion exposures. Physically active patterns had the highest
      prevalence in construction/agriculture/mining, followed by (in order)
      wholesale/retail trade, utilities, manufacturing, services, government, and
      finance/insurance. Physically passive patterns tended to reverse this order, and
      repetitive motion followed a third pattern. Physically active risk factors were
      typically higher for males, though this varied by industry and occupation. All
      risk factors except for stress show a steady decrease with age. CONCLUSION:
      Almost 1,000,000 Connecticut workers are estimated to be exposed to repetitive
      work, bent wrists, and job stress. Workers in high exposure industries and
      occupations should be closely evaluated for risks, with outreach to industries
      for preventive ergonomic interventions as preferred to treatment for conditions
      that arise.

PMID- 17526382
TI  - Multiple fractures in a woman receiving 24 years of etidronate treatment for
      Paget's disease.

PMID- 17526383
TI  - Incidence of skin melanoma in Connecticut towns and counties, 1997-2003.
AB  - Incidence rates for malignant melanoma of the skin have continued to rise in
      Connecticut and other populations covered by high-quality population-based cancer
      registries. Known risk factors include periodic intense exposure to ultraviolet
      radiation, such as excessive tanning efforts and sunburns. Numbers of melanomas
      diagnosed in 1997-2003 by town of residence in Connecticut were examined in
      relation to the numbers expected on the basis of statewide incidence rates. Of
      the 24 towns located directly on the ocean shoreline, 15 (62.5%) had a
      statistically significant elevated number of melanomas in males and/or females,
      or when data for both sexes were combined. Analysis of melanoma incidence rates
      by county showed considerable variation, with highest rates in New London county.
      Primary prevention efforts for both children and adults should include physician
      advice for high-risk patients regarding excessive exposure to ultraviolet
      radiation, and statewide public health efforts that take into account the
      geographic patterns.

PMID- 17526384
TI  - Enteric peritonitis caused by Clostridium perfringens in peritoneal dialysis.
AB  - Peritonitis is a common complication in peritoneal dialysis (PD). Epidemiology of
      the causative organism varied over time, but anaerobes are still extremely rare.
      We describe a second reported case of Clostridium perfringens peritonitis in a
      peritoneal dialysis patient since 1998. The patient presented with PD-related
      peritonitis that did not respond to the antibiotic choice recommended by the
      International Society of Peritoneal Dialysis guidelines. We used
      piperacillin/tazobactam with good result, when the dialysate culture revealed a
      gram-positive anaerobe. We postulate that Clostridium perfringen came from an
      enteric source by translocation. A few studies have implicated diverticular
      disease and gastric acid inhibitors in PD-related enteric peritonitis, and the
      results are still controversial. Further study is needed to establish a
      correlation between bowel pathology and enteric peritonitis in peritoneal
      dialysis patients.

PMID- 17526385
TI  - Nonmidline intracranial lipoma misdiagnosed as meningioma: case report.
AB  - A patient was initially believed to have a cavernous sinus and sphenoid ridge
      meningioma and presented to the University of Connecticut Health Center for
      radiation therapy. Initial radiation planning computerized tomography (CT)
      revealed the mass to be a lipoma. Conservative management with serial monitoring
      was the revised plan. This paper describes the rare entity of an intracranial
      lipoma not located in the midline, and some pitfalls in imaging of intracranial
      masses.

PMID- 17526386
TI  - Radiology then and now: personal recollection.

PMID- 17526387
TI  - Throwing away older physicians.

PMID- 17526388
TI  - Primary care at the tipping point.

PMID- 17526389
TI  - Drug company--physician communication challenged.

PMID- 17526390
TI  - Social welfare and the M.D. 1957.

PMID- 17526391
TI  - Resilience and mental health.

PMID- 17526392
TI  - Re: "The state of physician office-based health information technology in
      Connecticut".

PMID- 17526393
TI  - [Chronic obstructive pulmonary disease].
AB  - COPD represents an underestimated and underdiagnosed disease with an enormous
      socioeconomic impact. Cigarette smoking is the main risk factor for the
      development of COPD. For this reason, prevention and smoking cessation form the
      mainstays of COPD therapy. During the last years, huge progress has been made in
      the understanding of the underlying pathophysiological processes and in the
      development of new therapeutic interventions that are different from that used in
      Asthma bronchiale. Long acting bronchodilators are the basis of COPD maintenance
      treatment. Besides the improvement in lung function they reduce dyspnoea and
      improve exercise tolerance and quality of life. However, in addition to
      pharmacological therapy intensive pharmaceutical care is crucial for COPD
      patients. Thus, pharmacists can contribute significantly to a successful
      management of the widespread disease COPD.

PMID- 17526394
TI  - [In case of risks and side effects: ask your genes, too].
AB  - The medical literature reports between 5 and 17% of all hospitalisations to be
      due to side effects or interactions of drugs. These effects may be caused by
      genetic or non-genetic factors. The influence of genes on the pharmacology of
      drugs has been studied intensively during the last years. However, only one
      diagnostic test for two of these genes is currently commercially available.

PMID- 17526395
TI  - [Naratriptan. A new medical option for the pharmacist].

PMID- 17526396
TI  - [Aerosol administration-- appropriate treatment for asthma in a "recovered
      alcoholic"?].

PMID- 17526397
TI  - Put onus on vendors to meet your security and safety requirements.

PMID- 17526398
TI  - Standardize and synchronize product data for safety.

PMID- 17526399
TI  - Illinois health system realizes millions in cost savings.

PMID- 17526400
TI  - Three top areas where supply chain execs go wrong.

PMID- 17526401
TI  - [Anatomy lessons on animals].
AB  - The first anatomical studies were realized on the animal by Galen and Vesalius.
      Bourgelat created the first veterinarian school in Lyons, then in Paris where the
      famous dissection of a man on his horse can be seen (Fragonard). The Lafosse
      dynasty was interested in the study of the horse care and the painter Sollier
      showed the most beautiful coloured engravings about the horses. A chair of
      anatomy was created to compare the human and animal anatomy by the school of
      Jardin des Plantes en 1855.

PMID- 17526402
TI  - [The first printed essay on illustration colors completing the 1911 lecture of
      professor Rene Ledoux-Lebard].
AB  - The author proposes to complete the lecture of Professor Rene Ledoux-Lebard
      published in 1911 in the Bulletin de la Societe Francaise d'Histoire de la
      Medecine about the first printed essay of colour illustration. He deals with the
      origins of the graving and its defaults at the beginning of the Renaissance and
      he insists upon the historical anatomic and physiological interests of graving
      such as the picture of a gravid woman with the cord linking the womb to the
      breast.

PMID- 17526403
TI  - [The matrix speculum of Recamier].
AB  - The matrix speculum probably appeared in the first century as a bronze
      instrument: it was dug out of the ruins of Pompei and was still used at the
      beginning of the twentieth century. In 1804-1806. Recamier used a slender tin
      tube to treat the ulcers of uterus and his tube quickly became conical and then
      appeared a double tin "leaflet" speculum. Four main reasons explain the great
      success : the smooth wall of the tube, the choice of tin to have a good lighting
      during the clinical examination, the conical design for anatomical reasons and
      the veneral diseases in Recamier's period.

PMID- 17526404
TI  - [The work of R.T.H. Laennec at the Necker Hospital, then Charity Hospital from
      1821 to 1826].
AB  - His bad health obliged RTH Laennec to interrupt his hospital activities from 1819
      to 1821. He goes back to his head functions in Necker's then Charity's Hospitals
      from 1821 to 1826. His others activities, especially teaching, affect his busy
      time table. His unit's recruitment is less specialized in thoracic pathologies
      than it was from 1816 to 1819. It is true that his "College of France Lessons" as
      his lectures, in the faculty of medicine concern all the clinical aspects. So the
      links between hospital activities and the second edition of his Treaty are not so
      strong as they were with the first one.

PMID- 17526405
TI  - [The place of consultation in medicine "carries" the hospital Saint-Anthony
      (Paris) in the fight against the production of German war by the sabotage of the
      service of obligatory work (S.T.O.), 1943-1944].
AB  - During the World War II Germany had to improve its production of war through
      recruiting workers particularly in foreign countries like France. The medical
      centre of the Hospital Saint-Antoine Paris succeeded to let escape about 1 500
      workers through false diagnoses or fake medical records.

PMID- 17526406
TI  - [Military surgeon Henry Gabrielle (September 1887 - April 1968)].
AB  - As a military surgeon Henry Gabrielle had a heroic behaviour during the World War
      I. He was appointed professor of surgery at the hospital Val-de-Grace in 1919 and
      in 1926 he became professor of anatomy at the Faculty of Medicine in Lyon. His
      action in the French Resistance was so significant that he was appointed Health
      Director of the Region Rhone Alpes. As president of the hospitals of Lyon from
      1952 his role of organisation was important.

PMID- 17526407
TI  - [French colonial military medicine. A medical adventure of three quarters of a
      century (1890-1968)].
AB  - The French colonial medicine lasted from 1890 to 1968 in the tropical countries
      of Africa, Asia and America. The Medical Doctors and Pharmacists went from the
      military schools of Bordeaux and Lyon and worked upon 11 millions km2 to fight
      against the big endemic and contagious scourges within the local populations.
      Beside an itinerant medicine, some medical posts were created in the bush and
      some hospitals were built in the towns. Later some autochthonous schools were
      created and became Faculties of Medicine. 14 institutes of Pasteur made up the
      organisation. As the Medical Doctors and the Pharmacists were military they
      participated in the two World Wars and the colonial wars. As the product of an
      epoch, the colonial M.D. was also, the consequence of the ambiguity of his
      civilian and military status.

PMID- 17526408
TI  - [Bruno Giraud (1768-1811), "first surgeon" to Louis Bonaparte, king of Holland].
AB  - In 1806 Bruno Giraud (1768-1811), as an assistant to the head of the surgical
      department of the "Hotel-Dieu" (Paris), was appointed personal surgeon to King
      Louis Bonaparte of Holland in 1806 and chief surgeon of the Dutch army. In 1809
      he was appointed professor of practical surgery at the Atheneum Illustre
      (Amsterdam), which position he held until July 1810. After his return to Paris,
      he resumed his former job at the Hotel-Dieu.

PMID- 17526409
TI  - [The difficulty in assessing the wounds of the officers of the Napoleonic
      armies].
AB  - About any difficulties of assessment of the injuries of Napoleonic army officers.
      A gravely injured military was often injured again a few days later so doubt can
      occur about the reality of the firts injury. Then through the different cases the
      remark is frequent without satisfactory explanation.

PMID- 17526410
TI  - [Jean-Charles Sournia and Berry].
AB  - A previous Eloge has been pronounced on June 30, 2001 during the work session of
      the French and the International Societies of History of Medicine. It was devoted
      to the various aspects of the medical, historical and public career of Prof Jean
      Charles Sournia (November 24, 1917-June 8, 2000). The present session of the
      French Society of History of Medicine hold in Bourges, on June, 18, 2005 is an
      accomplishment of the wish of this child of Bourges, the capital of Berry. In
      this intoductive paper, from family testimonies and photographies, details are
      given about the childhood of Jean-Charles Sournia in Berry, his scholarship and
      his family. Sournia was deeply attached to the family house, to the city where he
      was born and to its hospital, called hotel-Dieu.

PMID- 17526411
TI  - [Who was the "Dame de Beaute?" Scientific study of the remains of Agnes Sorel].
AB  - According to her last will Agnes Sorel has been buried in the Collegiate Church
      Saint-Ours de Loches. The transfer from Logis Royal gave the opportunity to
      authenticate her ashes and to clarify the year of her birth, the cause of her
      death or ... the colour of her hair.

PMID- 17526412
TI  - [History of the renovation of the hotel-Dieu of Bourges].
AB  - From the 16th to the 20th century "hotel-Dieu" was the main hospital in the Berry
      capital. In the 30's the mayor decided to renovate the building but in 1994 the
      construction of a new hospital--"Centre Hospitalier Jacques-Coeur"--freed the
      ancient building which became a historical centre for culture et tourism in the
      region.

PMID- 17526413
TI  - [Medical mythology and etymologies].
AB  - The lecture is an allusion to Sournia's work and his book "Mythologies de la
      medecine moderne". (P.U.F 1969). The author evokes the origins of medical terms
      such as psyche, hermaphrodite, nymphomania, aphrodisiac, marcissism, hypnotism,
      etc.

PMID- 17526414
TI  - [Hospitals, leper-houses and holy healers and in medieval Berry].
AB  - Around the year 1000 many problems have been put throughout the beginning of
      urbanization, the increase of the country people, the pilgrimages and the
      spreading trade. The study of the medieval Charts allows to clarify how the sick
      were cured in the first hospitals-hotels-Dieu- and how the lepers were isolated
      and kept outside the cities. When the recovery was impossible the intercession of
      saints was the only hope for the knight as well as for the peasants.

PMID- 17526415
TI  - [Obsession-impulsion infanticide].
AB  - In 1836, the case-history of a young mother, the victim of a phobia of the
      impulsion to murder her infant. Esquirol considers her case as one of homocidial
      monomania, and classifies her among psychotic patients who have actually killed.

PMID- 17526416
TI  - [When Esquirol wrote to the sub-prefect of Foix "High Pyrenees"].
AB  - Communication about a letter from Esquirol on 18th January 1814 in which he asked
      to the "sous-prefet de Foix" investigations on this insane and strange behaviour
      of this "wild-woman" found nude in the landscape of the Pyrenees ariegeoises.
      Esquirol also riquiered begiven the insane woman skull's who died in jail. So he
      can compare this one with others skulls he collected and study before from
      melancholics patients. The most important interest in this letter is showing us
      how Esquirol was fascinate himself by "l'ensauvagement" (Pinel aud Itard
      Influence).

PMID- 17526417
TI  - [The law on the insane of June 30, 1838].
AB  - The Law of 30th June 1838 for the insane, voted practically unanimously by the
      two Chambers, made it obligatory for each Dipartement to have an establishment
      specifically for the treatment of the insane. The Law made lengthy arrangements
      about admissions--official or voluntary--also the arrangements for the
      maintenance or the departure of patients placed in these treatment centres. The
      administrative authorities, and above all the Prefet, as well as the judicial
      authorities, must regularly visit these establishments, to examine the possible
      complaints of the patients and to control the application of the Law. The doctors
      were held responsible for the certificates describing the state of the person and
      his need to remain in care, or the possibility of his leaving. The protection and
      the freedom of the individual, which could have been put in jeopardy by
      committal, was the major preoccupation of the legislators in 1838. The Law of
      30th June 1838 has been replaced by that of 27th June 1990 which has kept all the
      essential measures.

PMID- 17526418
TI  - [When Paul Bourget frequented the "Infirmerie speciale"].
AB  - Paul Bourget, the famous novelist, in his times, met Ernest Dupre, the titular of
      the professorship for psychiatry and consultant in the "Infirmerie speciale" and
      became a frequenter of many psychiatric facilities, among them the "Infirmerie
      speciale". Accordingly we study the relations between Belles-Lettres and
      psychiatric literature.

PMID- 17526419
TI  - [Death by starvation in French psychiatric hospitals during the occupation].
AB  - The author reports the tragic event which happened in the psychiatric hospitals
      where several thousands patients died by starvation during the occupation. He
      treats with a judicial inquiry in the wake of the death of fifteen patients in
      the psychiatric hospital of Toulouse.

PMID- 17526420
TI  - Protein kinase A activity and protein phosphorylation in the haemocytes of immune
      challenged Galleria mellonella larvae.
AB  - Protein kinase A (PKA) activity was detected in the haemocytes of greater wax
      moth, Galleria mellonella larvae using a specific peptide substrate--kemptide.
      The enzyme was activated in vitro by 1 microM concentration of cAMP, 8-Br-cAMP, 8
      Chl-cAMP and BzcMP, whereas in the case of cGMP 10 microM concentration was
      necessary. Immune challenge of G. mellonella larvae with bacteria led to changes
      in haemocyte PKA activity. Gram-positive M. luteus was a better inducer of PKA
      activity than Gram-negative E. coli. The kinetics of activity changes was
      dependent on the bacteria used and considerably differed from that observed in
      water-treated insects. Inhibition of PKA activity by cell-permeable, specific
      inhibitor, Rp-8-Br-cAMPS, induced changes in haemocyte morphology resembling
      those caused by live bacteria. Four potential PKA substrates of 155 kDa, 44 kDa,
      40 kDa and 22 kDa were recognized in the haemocytes of naive larvae by phospho
      motif antibodies for PKA phosphorylation consensus site. The modification level
      of 40 kDa protein changed after water treatment and immune challenge of G.
      mellonella larvae, whereas that of 155 kDa protein changed only after E. coli and
      LPS injections. Additionally, in the haemocytes of bacteria- and LPS-challenged
      insects a transient phosphorylation of 36 kDa protein was detected.

PMID- 17526421
TI  - Identification and hepatic expression profiles of cytochrome P450 1-4 isozymes in
      common minke whales (Balaenoptera acutorostrata).
AB  - Full-length cDNA sequences of cytochrome P450 (CYP) 2C78, 2E1, 3A72, 4A35 and 4V6
      isozymes were isolated from a hepatic cDNA library of common minke whale
      (Balaenoptera acutorostrata). The deduced amino acid sequences of minke whale
      CYP2C78, 2E1, 3A72, 4A35 and 4V6 showed high identities with cattle CYP2C86
      (83%), pig CYP2E1 (85%), sheep CYP3A24 (82%), pig CYP4A21 (80%), and human CYP4V2
      (76%), respectively. To investigate whether or not these CYP expression levels
      are altered by contamination of organochlorine contaminants (OCs), mRNA levels of
      these CYPs in the liver of common minke whale were measured using a quantitative
      real-time RT-PCR method, and the quantified mRNA levels were employed for the
      statistical analysis with the residue levels of OCs including PCBs, DDTs (p,p'
      DDT, p,p'-DDD and p,p'-DDE), chlordanes (cis-chlordane, trans-chlordane, cis
      nonachlor, trans-nonachlor and oxychlordane), HCHs (alpha-, beta- and gamma
      isomers) and hexachlorobenzene that have already been reported elsewhere.
      Spearman's rank correlation analyses showed no significant correlation between
      CYP expression levels and each OC level in the common minke whale liver, implying
      that these environmental chemicals have no potential to alter the expression
      levels of these CYPs or the residue levels encountered in the whale livers may
      not reach their transcriptional regulation levels. This suggests that the
      expression of individual CYPs in the whale liver may be at basal level.
      Relationships among hepatic mRNA expression levels of these CYP2-4 isozymes
      together with CYP1A1 and CYP1A2 were also examined. Significant positive
      correlations were detected among mRNA expression levels of individual CYP
      isozymes in most cases. These associations indicate that the transcriptional
      regulation of these CYPs examined in this study may be reciprocally related.
      CYP1A1 levels showed a positive correlation with CYP1A2 levels (r=0.64, p<0.01)
      indicating that both CYP isozymes were regulated by aryl hydrocarbon receptor
      activated by endogenous ligands. A strong positive correlation between CYP2C78
      and 3A72 (r=0.90, p<0.001) suggests that expression of these CYP isozymes may be
      under a regulation mechanism of cross-talk in which specific nuclear receptors
      such as constitutive androstane receptor and pregnane X receptor are involved.
      The present study indicates that minke whale from the North Pacific may be a
      model species to investigate the mechanism of basal regulation of these CYPs.

PMID- 17526422
TI  - Intermittent preventive treatment of malaria in pregnancy: a community-based
      delivery system and its effect on parasitemia, anemia and low birth weight in
      Uganda.
AB  - OBJECTIVE: The main objective of the study was to assess the impact of a
      community-based delivery system of intermittent preventive treatment (IPT) for
      malaria in pregnancy with sulfadoxine-pyrimethamine (SP) on access, parasitemia,
      anemia and low birth weight as primary outcome measures. METHODS: A study was
      designed to test the community-based delivery system of IPT through traditional
      birth attendants (TBAs), drug-shop vendors (DSVs), community reproductive health
      workers (CRHWs) and adolescent peer mobilizers (APMs), and to compare these with
      IPT at health units in an area of high malaria transmission - Mukono District,
      Uganda. RESULTS: Two thousand seven hundred and eighty-five pregnant women
      participated in the study. The majority of the women (92.4%) at the community
      based approaches received their first dose of IPT during their second trimester
      compared to 76.1% at health units (p<0.0001). At both health units and the
      community-based approaches, IPT increased mean hemoglobin by 6.7% (p<0.0001) for
      all parities and by 10.2% among primigravidae. IPT reduced the prevalence of
      severe anemia from 5.7% to 3.1% (p<0.04). The prevalence of parasitemia was
      reduced from 24.5% to 16.1% (p<0.001), and parasite density reduced significantly
      (p<0.02) after the first dose and remained stable with the second dose. Overall
      the proportion of low birth weight was 6.3% (8.3% at health units versus 6.0% at
      the community-based approaches, p<0.03) highlighting the importance of access and
      adherence to IPT. This intervention was acceptable to 89.6% of the women at the
      community-based approaches intending to use IPT in the future, while 48.1% of
      them had recommended it to other women. CONCLUSIONS: The community-based
      approaches increased access and adherence to IPT with an effect on anemia, severe
      anemia, parasitemia and low birth weight. However the reduced effect of IPT on
      parasitemia points to drug resistance with SP and this requires further
      evaluation; research into the identification of other more efficacious drugs for
      malaria prevention in pregnancy is also required.

PMID- 17526426
TI  - Comment on "DNA ploidy in proliferative verrucous leukoplakia".

PMID- 17526423
TI  - Flightless I: an actin-remodelling protein and an important negative regulator of
      wound repair.
AB  - Flightless I (FliI) is a member of the gelsolin family of actin-remodelling
      proteins, and has been identified as having two functional protein family
      domains: a leucine rich repeat (LRR) domain and a gelsolin-like domain. This
      unique structure allows FliI to act as an actin-remodelling protein as well as a
      nuclear receptor co-activator with ability to interact with various other
      proteins important in cellular signaling. The actin cytoskeleton is an integral
      component of all cells and the effect of FliI protein on actin remodelling is a
      vital part of cellular motility, contraction and adhesion. The product of the
      FliI gene is expected to provide a vital link between the molecules of yet
      unidentified signal transduction pathways and the actin cytoskeleton. Exact
      signaling pathways and mechanisms underpinning FliI effects in wound healing are
      yet to be fully identified however strong research evidence clearly identifies
      this molecule as a possible new therapeutic target whose manipulation may greatly
      improve wound healing and could lead to potential innovative medical
      applications.

PMID- 17526427
TI  - Identification of polycyclic aromatic hydrocarbons (PAHs) in soil by constant
      energy synchronous fluorescence detection.
AB  - In this paper, a novel method of constant energy synchronous fluorescence (CESF)
      was proposed to the simultaneous determination of different polycyclic aromatic
      hydrocarbons (PAHs) in a mixture of 16 components. When different appropriate
      intervals of the constant energy (Deltanu=1400 or 4800cm(-1)) were chosen during
      constant energy synchronous scanning, 13 PAHs could be identified and quantified
      by the corresponding synchronous spectra. Results show that their linear
      relations are fine and the limits of detection (LODs) were between 0.2 and
      7.6ngml(-1). Then the application of CESF method proposed in the analysis of the
      real soil samples under the optimum conditions indicated that 11 PAHs could be
      identified and the total concentration of PAHs in a real soil sample is 5.1microg
      g(-1), most of PAHs in the soil samples had three or four rings. Recoveries of
      these PAHs were from 70.9 to 121.4% in most cases. This CESF method is a simple,
      rapid, sensitive method with high resolution and also suitable to analyze the
      complex mixtures of PAHs in other environmental samples.

PMID- 17526428
TI  - Viability of infectious viral particles of HIV and BMCs in breast milk.
AB  - BACKGROUND: Infectious factors in breast milk such as viral particles and living
      infected cells are of prime importance in the transmission of HIV by
      breastfeeding. OBJECTIVES: To perform effective approaches for reducing HIV
      transmission via breastfeeding, we investigated the biological importance of
      infectious viral particles and infected BMCs in breast milk. STUDY DESIGN:
      Alteration of viral infectivity was monitored using a modified experimental
      infection assay that exploited the cytotoxicity of breast milk, and BMC viability
      was evaluated by flow-cytometric analysis. RESULTS: Infectious viral particles
      were found to decrease time-dependently after contact with breast milk, whereas
      BMCs showed prolonged survival in breast milk. CONCLUSIONS: The biological
      importance of infected BMCs in breast milk for the transmission of HIV via
      breastfeeding was considered.

PMID- 17526429
TI  - Presence of hepatitis B virus core promoter mutations pre-seroconversion predict
      persistent viral replication after HBeAg loss.
AB  - BACKGROUND: In patients with chronic hepatitis B virus (HBV) infection DNA levels
      do not always fall after anti-hepatitis B e (anti-HBe) seroconversion.
      OBJECTIVES: To follow longitudinally through HB e antigen (HBeAg) loss HBV DNA
      levels and core promoter/precore sequences in a cohort of 21 chronic HBV
      carriers. STUDY DESIGN: Treatment-naive HBeAg seropositive HBV carriers were
      monitored through HBeAg loss for between 2 and 22 years (mean 9.3). Core
      promoter/precore sequences, genotypes, HBV DNA levels and HBe status were
      determined. RESULTS: Patients were grouped into those in whom serum/plasma HBV
      DNA remained high after HBeAg loss (group 1, n=11; HBV DNA>5log(10)IU/ml) and
      those in whom HBV DNA declined (group 2, n=10). Re-appearance of HBeAg was seen
      in seven group 1 patients. Pre-seroconversion mutations in the core promoter
      region including A1762T and/or G1764A were detected more frequently in group 1
      (P=0.031). Overall sequence changes at sites other than 1762/1764 were more
      common post-seroconversion in group 1 than group 2 patients (P=0.037).
      CONCLUSIONS: The presence of core promoter mutations prior to HBeAg loss
      identified those patients in whom HBV DNA persisted at high levels and was
      associated with temporary re-emergence of serum HBeAg. These patients may benefit
      from early anti-viral treatment.

PMID- 17526430
TI  - Influenza A/H5N1 virus infection in humans in Cambodia.
AB  - BACKGROUND: Between January 2005 and April 2006, six patients of influenza A/H5N1
      virus infection were reported in Cambodia, all with fatal outcome. OBJECTIVES: We
      describe the virological findings of these six H5N1 patients in association with
      clinical and epidemiologic findings. STUDY DESIGN: Broncho-alveolar lavage,
      nasopharyngeal, throat and rectal swabs and sera were cultured for virus
      isolation and viral load quantified in clinical specimens by real-time RT-PCR. We
      compared sequences obtained from different body sites within the same patient to
      detect viral quasi-species. RESULTS: H5N1 virus strains isolated in Cambodia
      belong to genotype Z, clade 1 viruses. H5N1 viruses were isolated from serum and
      rectal swab specimens in two patients. The haemagglutinin gene sequences of the
      virus in different body sites did not differ. Amino acid substitutions known to
      be associated with a change in virus binding were not observed. CONCLUSION: The
      high frequency of virus isolation from serum and faecal swabs highlights that
      H5N1 is likely to be a disseminated infection in humans and this has implications
      for antiviral treatment, biosafety in clinical laboratories and on risks for
      nosocomial and human-to-human transmission. There were no tissue-specific
      adaptive mutations in the HA gene from viruses isolated from different organs.

PMID- 17526431
TI  - Meeting report: International Symposium on Ciliate Biology held at Sri Guru Tegh
      Bahadur (SGTB) Khalsa College, University of Delhi, February 6-7, 2007.

PMID- 17526432
TI  - Matrix replenishment by intervertebral disc cells after chemonucleolysis in vitro
      with chondroitinase ABC and chymopapain.
AB  - BACKGROUND CONTEXT: One of the advantages of chemonucleolysis for the treatment
      of a herniated intervertebral disc is the potential for the disc to self-repair.
      It has been suggested that the enzymes used for chemonucleolysis differentially
      affect the potential of the disc cells to promote repair. PURPOSE: To test the
      ability of nucleus pulposus and anulus fibrosus cells to repair the extracellular
      matrix degraded in vitro by either chondroitinase ABC or chymopapain. STUDY
      DESIGN: An alginate cell culture system was used to monitor the progress of
      matrix repair after chemonucleolysis in vitro. METHODS: Rabbit nucleus pulposus
      or anulus fibrosus cells precultured for 10 days in alginate gel were briefly
      exposed to low concentrations of chondroitinase ABC or chymopapain and then
      returned to normal culture conditions for up to 4 weeks. At each time point, the
      contents of DNA and matrix macromolecules and proteoglycan synthesis were
      measured. RESULTS: The DNA content of enzyme-treated alginate beads during the
      following 4 weeks of culture was higher in the chondroitinase ABC group than in
      the chymopapain group (NP, p<.01, and AF, p<.05). The content of proteoglycan in
      beads containing nucleus pulposus and anulus fibrosus cells in the chondroitinase
      ABC group was higher than that in the chymopapain group (NP and AF, p<.001). The
      rate of proteoglycan synthesis and the content of collagen did not, however,
      differ between those two groups. CONCLUSIONS: Intervertebral disc cells exposed
      to chondroitinase ABC reestablish a matrix richer in proteoglycan than cells
      exposed to chymopapain. This may be because of differences in the substrate
      spectrum of each enzyme. Although these results cannot be translated directly to
      the in vivo situation, they suggest the possibility that cells in discs subjected
      to chondroitinase ABC-induced chemonucleolysis retain a greater ability to
      replenish their extracellular matrix with proteoglycans than cells in discs
      exposed to chymopapain.

PMID- 17526433
TI  - Adverse swelling associated with use of rh-BMP-2 in anterior cervical discectomy
      and fusion.

PMID- 17526434
TI  - Vertebral osteolysis after posterior interbody lumbar fusion with recombinant
      human bone morphogenetic protein 2: a report of five cases.
AB  - BACKGROUND: Recombinant human bone morphogenetic protein 2 (rh-BMP-2) is
      frequently used in an off-label fashion. Its application for posterior interbody
      fusion appears intuitive because its use obviates the need for iliac crest bone
      graft and shows higher fusion rates than with the use of local autologous bone
      graft. To date, there is no report of adverse outcomes with such use of rh-BMP-2.
      PURPOSE: To draw attention to this unusual complication of posterior interbody
      lumbar fusion and to review the relevant literature. STUDY DESIGN: Clinical
      report of five cases of vertebral osteolysis that developed postoperatively from
      lumbar transforaminal interbody fusion of the L5/S1 motion segment using cages
      and rh-BMP-2. METHODS: Sixty-eight patients underwent transforaminal lumbar
      interbody fusion for spondylolisthesis or degenerative disc disease with
      discogenic back pain. Five of these 68 patients developed vertebral osteolysis
      within 4 months from their surgery. Their clinical presentation and radiographic
      findings are presented in this case series. RESULTS: Each one of these five
      patients had uneventful surgery and postoperative recovery. Their back and leg
      pain improved in the immediate postoperative period. However, each patient
      reported worsening back pain with variable radicular pain as early as 4 weeks and
      as late as 3 months after the index procedure. Diagnostic workup revealed
      evidence of vertebral osteolysis typically involving the L5 vertebral body. In
      all five patients, osteolytic defects filled in spontaneously, and symptoms
      typically resolved within an additional 3 months of nonoperative care.
      CONCLUSIONS: Vertebral osteolysis can occur with the use of rh-BMP-2 in posterior
      lumbar interbody fusions. Violation of the end plate during decortication may be
      a contributing factor. Symptoms often resolve spontaneously.

PMID- 17526435
TI  - Fixation strength of unicortical versus bicortical C1-C2 transarticular screws.
AB  - BACKGROUND CONTEXT: The internal carotid artery and hypoglossal nerve lie over
      the anterior aspect of the lateral mass of the atlas and are at risk from
      bicortical C1-C2 transarticular screws. This has led to the recommendation for
      unicortical screws if the neurovascular structures are in close proximity to the
      proposed exit point. No data are available on strength of unicortical versus
      bicortical C1-C2 transarticular screws. PURPOSE: To compare the biomechanical
      pullout strength of unicortical versus bicortical C1-C2 transarticular screws in
      a cadaveric model. STUDY DESIGN: Biomechanical study. METHODS: Fifteen cervical
      spine specimens underwent axial pullout testing. A unicortical C1-C2
      transarticular screw was placed on one side with a contralateral bicortical
      screw. Data were analyzed to reveal any significant differences in strength.
      RESULTS: Mean pullout strength for the bicortical C1-C2 transarticular screws was
      1,048.8 (+/-360.1) N versus 939.2 (+/-360.6) for unicortical screws (p=.22).
      There was no significant difference in the pullout strength of unicortical and
      bicortical screws. CONCLUSIONS: In cases with satisfactory bone quality, it
      appears reasonable to use unicortical screws to avoid the risk of neurovascular
      injury from penetrating the anterior cortex of C1.

PMID- 17526436
TI  - The perioperative cost of Infuse bone graft in posterolateral lumbar spine
      fusion.
AB  - BACKGROUND CONTEXT: There is mounting evidence supporting the efficacy of bone
      morphogenetic protein (BMP) for both anterior interbody and posterolateral lumbar
      fusion. However, the relative cost of BMP remains an important concern for
      physicians, hospitals, and payers. PURPOSE: The purpose of this study is to
      report on the perioperative costs for patients treated with rhBMP-2 as compared
      with an iliac crest bone graft (ICBG) supplemented with graft extenders. STUDY
      DESIGN/SETTING: A prospective randomized controlled trial of rhBMP-2/ACS (Infuse
      Bone Graft; Medtronic Sofamor Danek, Memphis, TN) versus ICBG+/-graft extender
      for lumbar spine fusion in patients over 60 years old. PATIENT SAMPLE: One
      hundred two patients over 60 years old who required a posterolateral lumbar spine
      fusion randomized between receiving rhBMP-2/ACS or ICBG. OUTCOME MEASURES: All
      health-care costs over the first 3 months after surgery. METHODS: As part of a
      prospective randomized trial of rhBMP-2/ACS versus ICBG+/-graft extender for
      lumbar spine fusion, all costs over the first 3 months after surgery were
      directly recorded by a dedicated coder funded by Norton Healthcare, Louisville,
      KY. A dedicated research nurse also followed all patients throughout their
      hospital stay and posthospitalization recovery to identify any adverse events or
      additional outpatient medical care. RESULTS: Fifty patients received rhBMP-2/ACS
      and 52 underwent ICBG harvest. The mean hospital cost for the index admission was
      $24,736 for the rhBMP-2/ACS group and $21,138 for the ICBG group. Mean inpatient
      physician costs were $5,082 in the rhBMP-2/ACS group and $5,316 in the ICBG
      group. Costs associated with posthospital rehabilitation averaged $4,906 in the
      rhBMP-2/ACS group versus $6,820 in the ICBG group. Total payer expenditure for
      the 3-month perioperative period averaged $33,860 in the rhBMP-2/ACS group and
      $37,227 in the ICBG group. CONCLUSIONS: The hospital carries the cost burden
      associated with the utilization of rhBMP-2/ACS. In contrast, the payer in a
      Diagnosis-Related Group (DRG) model achieves a net savings, based primarily on
      the decreased payment for inpatient rehabilitation, but also on decreased
      hospital reimbursement, physician costs, and other outpatient services.

PMID- 17526437
TI  - Development of mitochondria-specific mouse oligonucleotide microarray and
      validation of data by real-time PCR.
AB  - This study describes the development of a mitochondria-specific microarray,
      MitoChip, to measure transcripts of mitochondria-associated genes in various
      diseases and drug-induced toxicities in the mouse. The array consists of 542
      oligonucleotides that represent genes from the mitochondrial and nuclear genomes
      associated with mitochondrial structure and functions. The expression of
      mitochondrial genes was measured in the liver of both p53 haplodeficient (+/-)
      and wild-type (+/+) C3B6F(1) female mice exposed to antiretroviral agents,
      Zidovudine (AZT) and Lamivudine (3TC). Among genes whose expression was
      significantly altered, a set was selected for real-time PCR analysis to verify
      their differential gene expression. The real-time PCR data confirmed the
      observations by microarray analysis suggesting that the MitoChip may be an
      important tool for examining mitochondrial involvement in diseases and drug
      induced toxicities.

PMID- 17526438
TI  - In vivo pharmacokinetic and metabolism studies of ginsenoside Rd.
AB  - A high-performance liquid chromatography-electrospray ionisation-tandem mass
      spectrometry (LC-ESI-MS(n)) method has been developed to determine ginsenoside Rd
      in human plasma and to identify its metabolites in rat urine. The plasma and
      urine samples were pretreated by solid phase extraction (SPE) prior to analyses.
      In this work, gentiopicroside was used as the internal standard. The lower limit
      of quantification (LLOQ) for Rd in human plasma was 3 ng/ml. The average half
      life time in plasma was detected as 19.29 h, when 10 mg of ginsenoside Rd was
      administrated intravenously to the volunteers. Seven metabolites including three
      oxygenated, two combined and two hydrolyzed components were identified in rat
      urine samples by using LC-MS and MS-MS, when ginsenoside Rd administered either
      orally or intravenously.

PMID- 17526439
TI  - GC/MS analysis of the rat urine for metabonomic research.
AB  - In this paper, an optimized protocol was established and validated for the
      metabonomic profiling in rat urine using GC/MS. The urine samples were extracted
      by methanol after treatment with urease to remove excessive urea, then the
      resulted supernatant was dried, methoximated, trimethylsilylated, and analyzed by
      GC/MS. Forty-nine endogenous metabolites were separated and identified in GC/MS
      chromatogram, of which 26 identified compounds were selected for quantitative
      analysis to evaluate the linearity, precision, and sensitivity of the method. It
      showed good linearity between mass spectrometry responses and relative
      concentrations of the 26 endogenous compounds over the range from 0.063 to 1.000
      (v/v, urine/urine+water) and satisfactory reproducibility with intra-day and
      inter-days precision values all below 15%. The metabonomic profiling method based
      on GC/MS was successfully applied to urine samples from hyperlipidemia model
      rats. Obviously, separated clustering of model rats and the control rats were
      shown by principal components analysis (PCA); time-dependent metabonomic
      modification was detected as well. It was suggested that metabonomic profiling
      based on GC/MS be a robust method for urine samples.

PMID- 17526440
TI  - Tissue expanders in post-burn alopecia: supragaleal or subgaleal placement? In
      response to: Prakash, Tandon, Mantri 'Supragaleal placement of tissue expander
      for post-burn alopecia' Journal of Plastic, Reconstructive & Aesthetic Surgery
      2006;59:1102-1104.

PMID- 17526441
TI  - Temporary ectopic testicular replantation, refabrication and orthotopic transfer.
AB  - Bilateral traumatic castration if left untreated can result in permanent sexual,
      social and psychological maladjustments. We hereby report a novel procedure of
      temporary ectopic replantation of a traumatically avulsed testis on the forearm
      with refabrication and subsequent successful orthotopic microsurgical transfer to
      the perineum. The significance of this replantation is related to the
      refabrication of a long pedicle for subsequent reattachment to the perineum. This
      would not have been possible but for the ectopic replantation.

PMID- 17526442
TI  - Rational flap selection and timing for coverage of complex upper extremity
      trauma.
AB  - Reconstruction of complex extremity trauma continues to be a challenging task for
      plastic surgeons. Characteristics of such injuries include destruction of
      functional structures, often due to high energy trauma that causes significant
      invalidity. Before the era of free flaps, pedicled fasciocutaneous and muscle
      flaps were the only option for reconstruction of the severely injured upper
      extremity. The management of complex injuries of the upper extremity has changed
      with the development of reconstructive microsurgery. Nowadays, we have a great
      variety of different free flaps to cover defects of the upper extremity and
      restore function by innervated free flaps. Sensibility, skin thickness, texture,
      colour, durability, binding of the flap to the underlying structures, donor site
      morbidity, possibility of secondary reconstructive procedures, the surgeon's
      experience and operative facilities must all be taken into consideration for
      choosing the optimal reconstructive procedure. Not only the reconstructive und
      functional requirements but the timing of reconstruction is extremely important
      for final result. The purpose of this paper is to define the principles of flap
      selection and timing of flap reconstruction, according to the assessment of
      trauma in the upper limb.

PMID- 17526443
TI  - Uncombable hair syndrome: a clinical report.
AB  - Uncombable hair syndrome, also named "pili trianguli et canaliculi" or "cheveux
      incoiffables", is a rare structural anomaly of the hair shaft first reported in
      1973. Both inherited and sporadic forms have been described, characterized by dry
      and frizzy scalp hair that is impossible to comb. Diagnosis is suspected
      clinically and confirmed by scanning electron microscopy. The condition is
      usually isolated, however, several physical abnormalities can be associated. We
      report the case of a 2(1/2) year old-girl presenting isolated uncombable hair
      syndrome suspected clinically and confirmed by scanning electron microscopy.

PMID- 17526444
TI  - [Early arthritis].
AB  - Identifying the cause of polyarthritis can be difficult because of the extensive
      differential diagnosis. A thorough history and a complete physical examination
      are essential. Clinical factors such as disease chronology, inflammation,
      distribution, extra-articular manifestations, disease course are helpful in
      narrowing the possible causes. Many classic laboratory tests are nonspecific but
      these, together with specific tests and radiographs, may provide more useful
      diagnostic clues. Early arthritis may progress into established rheumatoid
      arthritis or another definite arthropathy, may resolve spontaneously, or may
      remain undifferentiated. To achieve better diagnosis and outcome in arthritis, it
      is important to recognize inflammatory arthritis first, then to establish the
      definitive diagnosis of arthritis and finally to estimate the risk of developing
      persistent or/and erosive irreversible arthritis to propose an optimal
      therapeutic strategy (within 3 months) in order to avoid joint destructions and
      function-loss and to provide a good quality of life.

PMID- 17526445
TI  - [Introduction of emotional labour into oncology].
AB  - Health care professionals do not have emotional labour obligations in their
      employment contract. However, in everyday work it is often inevitable for them to
      change their true feelings. This is critically true for professionals treating
      chronic or cancer patients. The suitable emotional state of the treatment staff
      does not only influence the practitioner-patient relationship but the process of
      recovery as well. Depending on the way one might get into the appropriate
      emotional state, the literature distinguishes between surface, deep and genuine
      acting. While surface and deep emotional labour has numerous negative
      psychological consequences genuine acting is usually accompanied by positive side
      effects. For those working in the field of oncology, emotional labour is a part
      of the role expectations of the professionals. This is how the appropriate
      attitude is a fundamental part of the professionals' essence. For the in depth
      analysis of subjects related to emotional labour, the authors adopted ideas from
      L. Festinger 's cognitive dissonance theory. The best way to alleviate cognitive
      dissonance and the negative side effects of emotional labour is to prevent the
      emergence of them. Oncology professionals should fit their role expectations
      genuinely, without particular efforts. If this was impossible, or the particular
      life situations did not allow genuine acting, it is the employer's and the
      workmates' common duty to help professionals, to ease the load of emotional
      labour, to diminish the occurring cognitive dissonance with the help of
      appropriate recompense.

PMID- 17526446
TI  - [Hepatitis A outbreak in Transdanubia (Hungary): molecular connections and
      epidemiological conclusions - 2006].
AB  - INTRODUCTION: Hepatitis A virus (HAV) is one of the most important cause of
      fecally transmitted acute infectious hepatitis worldwide. In Hungary, beside the
      sporadic HAV infections, outbreaks also occur, particularly in Northeast part of
      the country where the subgenotype IA is endemic. The reported number of HAV cases
      was less than 10 per year in Southwest Hungary. AIMS: A part of the European HAV
      surveillance, the author's aims were to follow and to analyze the outbreak of
      hepatitis A in Transdanubia (Southwest Hungary) in 2006 by molecular
      epidemiological methods. MATERIALS AND METHODS: Sera samples from symptomatic
      patients were tested prospectively by enzyme-immunoassay (EIA) and reverse
      transcription-polymerase chain reaction (RT-PCR) followed by sequence- and
      phylogenetic analysis. RESULTS: Between June and December 2006, a total of 115
      serum samples were positive for HAV IgM antibody in Southwest Hungary. Thirty
      (76.9%) of the 39 samples were RT-PCR-positive and contain genetically identical
      subgenotype IB hepatitis A virus (HAV/Transdanubia/2006/HUN) which has 100%
      nucleotide identity to strain IT-MAR-02 from Italy in 2002. Until now,
      approximately 1200-1300 persons have been infected with the probably imported
      strain. The average age of patients was 18 years (years 1 to 80). In this study,
      detailed clinical and epidemiological data of the outbreak are presented.
      CONCLUSIONS: Only a prospective molecular epidemiological study could verify the
      connection between the first sporadic HAV cases in June, the outbreak in August
      and the endemic spread of the virus since September in Southwest Hungary. This
      epidemic calls attention to how a hepatitis A outbreak can develop anywhere and
      at any time in Hungary and to the importance of active HAV immunization in the
      primary prevention.

PMID- 17526447
TI  - [Normal middle ear ventilation: a new theory].
AB  - According to our present knowledge, mainly due to O2 absorption the pressure
      continuously decreases in the normal middle ear, which is equalized by time to
      time opening of the Eustachian tube, so that air flows across the tube. AIM: The
      aim of the author is to revise this classic theory on the basis of his own
      research and the results of the last decades. The basic question is whether the
      pressure increases or decreases in the normal middle ear between two swallowings?
      PATIENTS AND METHODS: Middle ear pressure change was examined in 32 ears of 16
      healthy children in the swallowing pause (between two swallowings) with
      tympanometry. The patients were 14 +/- 5.2 years old. RESULTS: According to the
      results of the examinations, the middle ear pressure increases between two
      swallowings in healthy individuals, which is statistically significant (p =
      0.028). CONCLUSIONS: In his opinion this can only be explained by one factor, and
      that is CO2 diffusion. The pressure gradient of CO2 that is directed towards the
      middle ear cavity is upheld by the Eustachian tube - every time the tube opens
      the middle ear loses CO2 (the partial pressure of CO2 in the middle ear is
      higher, in the atmospheric air is very low), so after tube is closed, CO2
      diffuses from surrounding tissue to the middle ear and the pressure increases.
      This CO2 loss can take place if we consider that gases not only flow according to
      their composition percent, but also diffuse according to their partial pressure
      difference through the tube.

PMID- 17526448
TI  - [Attempts to reduce drug resistance of bacteria and cancer cells].

PMID- 17526450
TI  - [Festive inauguration of the first Hungarian School of Public Health at the
      University of Debrecen].

PMID- 17526451
TI  - [Novel drugs and therapeutics, supplement of the Orvosi Hetilap].

PMID- 17526453
TI  - [My memories of Professor Hamori--the misunderstood genius].

PMID- 17526454
TI  - [Regarding music and medicine].

PMID- 17526455
TI  - Female extrapair mate choice in a cooperative breeder: trading sex for help and
      increasing offspring heterozygosity.
AB  - Sexual conflict between males and females over mating is common. Females that
      copulate with extrapair mates outside the pair-bond may gain (i) direct benefits
      such as resources or increased paternal care, (ii) indirect genetic benefits for
      their offspring, or (iii) insurance against infertility in their own social mate.
      Few studies have been able to demonstrate the different contexts in which females
      receive varying types of benefits from extrapair mates. Here, I examined sexual
      conflict, female extrapair mate choice, and patterns of extrapair paternity in
      the cooperatively breeding superb starling Lamprotornis superbus using
      microsatellite markers. Although extrapair paternity was lower than many other
      avian cooperative breeders (14% of offspring and 25% of nests), females exhibited
      two distinct mating patterns: half of the extrapair fertilizations were with
      males from inside the group, whereas half were with males from outside the group.
      Females with few potential helpers copulated with extrapair mates from within
      their group and thereby gained direct benefits in the form of additional helpers
      at the nest, whereas females paired to mates that were relatively less
      heterozygous than themselves copulated with extrapair mates from outside the
      group and thereby gained indirect genetic benefits in the form of increased
      offspring heterozygosity. Females did not appear to gain fertility insurance from
      copulating with extrapair mates. This is the first study to show that individuals
      from the same population mate with extrapair males and gain both direct and
      indirect benefits, but that they do so in different contexts.

PMID- 17526456
TI  - Comparison of clozapine-amisulpride and clozapine-quetiapine combinations for
      patients with schizophrenia who are partially responsive to clozapine: a single
      blind randomized study.
AB  - Schizophrenia is a devastating psychiatric disorder. Clozapine has long been the
      gold standard for treatment of patients with treatment-resistant schizophrenia;
      however, some patients are only partially responsive to clozapine treatment.
      Augmentation of clozapine treatment might enhance its effectiveness in partial
      responders, but only a few studies have investigated possible augmentation
      strategies. This study compared the effectiveness and tolerability of the
      combination of amisulpride and clozapine with the combination of quetiapine and
      clozapine in patients who were only partially responsive to clozapine
      monotherapy. Fifty-six treatment-resistant patients who were partially responsive
      to clozapine were randomly assigned to receive amisulpride or quetiapine along
      with an ongoing stable dose of clozapine. Fifty patients completed the study.
      Patients were evaluated at baseline and at the first, third, sixth, and eighth
      weeks. Efficacy measures consisted of the Brief Psychiatric Rating Scale (BPRS),
      the Scale for the Assessment of Negative Symptoms (SANS), the Scale for the
      Assessment of Positive Symptoms (SAPS), and the Clinical Global Impression (CGI)
      scale. Tolerability and adverse effects were assessed with the Udvalg for
      Kliniske Undersogelser (UKU) Side Effect Rating Scale and the Simpson Angus Scale
      (SAS). A substantial improvement occurred in both groups by the end of the eighth
      week; however, the improvement associated with amisulpride was significantly
      greater than that seen with quetiapine. This difference was noted as early as the
      third week of follow-up in terms of CGI scores, and by the sixth week with regard
      to BPRS, SANS, and SAPS scores. Both drugs were well tolerated, as measured by
      UKU and SAS. Improvement favoring clozapine+amisulpride could be attributed to
      the selective D2/D3 binding property of amisulpride, which had an additional
      effect in improving symptoms of schizophrenia. The authors concluded that
      amisulpride seems to be effective and well tolerated for augmentation purposes in
      clozapine-resistant patients.

PMID- 17526457
TI  - Acute coronary syndrome: short-term effects of early intravenous metoprolol on
      maximum P wave duration and P wave dispersion.
AB  - In patients with acute coronary syndrome (ACS), the presence of atrial
      fibrillation (AF) results in worse inpatient outcomes than in those without AF.
      Two electrocardiographic markers, maximum P wave duration (P(maximum)) and P wave
      dispersion (P(dispersion)), have been assessed because they reflect conduction
      abnormalities in patients with paroxysmal AF. b blockers are known to have
      beneficial effects in patients with ACS. This prospective study was conducted to
      investigate whether early intravenous (IV) metoprolol injection acutely decreases
      P(maximum) and P(dispersion) in patients with ACS. This study involved 100
      consecutive patients with ACS who were divided into 2 groups according to whether
      or not they received early IV metoprolol. Group 1 consisted of 19 patients who
      received IV metoprolol within 3 h after onset of symptoms, and group 2 consisted
      of 81 patients who did not receive IV metoprolol within 3 h after symptom onset
      because of late admission. P(maximum) and P(dispersion) were measured on
      admission and again at 2 h after admission. Two-dimensional echocardiographic
      examination was also performed. For patients who received early IV metoprolol,
      P(maximum) and P(dispersion), measured 2 h after admission, were shorter than
      values at admission (P<.001). Conversely, P(maximum) and P(dispersion), measured
      2 h after admission, did not differ significantly from values at admission in
      patients who did not receive early IV metoprolol (P=.292 and P=.236,
      respectively). IV administration of metoprolol reduced values for P(maximum) and
      P(dispersion), measured 2 h after admission, among patients with ACS who were
      admitted within 3 h after onset of symptoms.

PMID- 17526458
TI  - Assessing itch in children with atopic dermatitis treated with tacrolimus:
      objective versus subjective assessment.
AB  - This study was undertaken to evaluate the clinical efficacy of tacrolimus for
      itch reduction in children with atopic dermatitis (AD). Seven children (3 boys
      and 4 girls) with AD were treated with topical tacrolimus for a consecutive 2-wk
      period after a 1-wk run-in. The clinical severity of AD was assessed with the
      SCORing Atopic Dermatitis (SCORAD) scale. Sleep disturbance, as reported by
      patients, and nocturnal scratching documented by a wrist movement monitor
      (DigiTrac), were evaluated at baseline and throughout treatment. The median
      (interquartile range) objective SCORAD scores before and after treatment were
      27.2 (24.8-36.7) and 23.9 (22.6-36.5), respectively (P=.248). Overall SCORAD
      scores before and after treatment were 36.1 (32.8-45.7) and 29.4 (24.8-45.4),
      respectively (P=.05). Scores on the itch and sleep disturbance components of the
      SCORAD were reduced from 5.0 (5.0-6.5) and 4.0 (3.5-5.0) to 4.0 (2.0-5.0) and 3.0
      (0.5-4.5), respectively. Total SCORAD was reduced in 6 patients (range, 8%-36%
      reduction) and remained similar in 1 patient. No significant change in the area
      or intensity component of the SCORAD was detected 14 d after treatment began
      (P=.48 and P=.115, respectively). Scratching activity, as documented by the
      DigiTrac movement recorder, was reduced from 115.0 g/min (64.8-215.5) to 71.5
      g/min (51.0-118.0) (P=.028) after 2 wk of treatment. Daily symptom scores (n=6
      pairs) for sleep disturbance reported separately each day by patients and parents
      correlated strongly with each other (intraclass coefficient, 0.60-0.98). The
      findings of this study show that tacrolimus is effective in relieving itch in
      children with AD. Investigators suggest that scratching movements, objectively
      measured with the use of DigiTrac, provide a reliable indicator of AD severity in
      children.

PMID- 17526459
TI  - Expression of soluble CD27 and interleukins-8 and -10 in B-cell chronic
      lymphocytic leukemia: correlation with disease stage and prognosis.
AB  - Investigators in this study explored levels of soluble CD27 (sCD27), interleukin
      (IL)-8, and IL-10 in B-cell chronic lymphocytic leukemia (B-CLL), and the
      correlation of these levels with disease stage and prognosis. Plasma IL-8, IL-10,
      and sCD27 levels were assessed with enzyme-linked immunosorbent assay tests in 22
      healthy donors and 70 patients with B-CLL (49 men and 21 women). Mean patient age
      was 61.57 y (range, 44-75 y). Mean healthy donor age was 62.09 y (range, 40-72
      y). In the study group, mean values were as follows: plasma IL-8, 284.758 pg/mL
      (0-1000 pg/mL) plasma IL-10, 26.152 pg/mL (0-100 pg/mL) sCD27, 731.357 U/mL
      (139.9-1000 U/mL) white blood cell count, 59.9 x 10(9)/L (0.8-250.0 x 10(9)/L)
      hemoglobin count, 11.2 g/dL (5.0-16.2 g/dL) platelet count, 162.5 x 10(9)/L (29.8
      317 x 10(9)/L) B(2) microglobulin (B(2)M) 3350.2 mg/L (274.7-7499.9 mg/L) CD38,
      19.5% and lactate dehydrogenase (count, 497.5 U/L (263.0-1507 U/L). Patients
      represented all Rai stages, with 22.9% at stage 0, 11.4% at stage I, 11.4% at
      stage II, 41.4% at stage III, and 12.9% at stage IV. Plasma levels of IL-8, IL
      10, and sCD27 were correlated between study and control groups; significantly
      higher IL-8 (P=.001) and sCD27 (P=.000) levels were found, but the IL-10 level
      was not significant (P=.139). Plasma IL-10 (P=.01) and sCD27 (P=.008) were
      positively correlated with Rai stage, but IL-8 was not (P=.146). Levels of sCD27
      were significantly correlated with values for B2M (P=.000), hemoglobin (P=.028),
      lactate dehydrogenase (P=.001), CD19 (P=.03), and IL-10 (P=.000). IL-8 was
      significantly correlated with white blood cell (P=.000) count, and CD38 (P=.001)
      and CD5 (P=.006) levels. IL-10 was significantly correlated with B(2)M (P=.017),
      CD19 (P=.000), platelet (P=.002), and CD27 (P=.000). In survival distributions
      for CD27, IL-8 and IL-10 were found to have more significant relationships for
      all parameters (P=.0000). In conclusion, the authors suggest that sCD27, IL-8,
      and IL-10 are more significant prognostic factors for B-CLL when compared with
      others, and these values should correlate with new prognostic factors (eg, zeta
      associated protein-70, mutated/unmutated immunoglobulin variable heavy chain).

PMID- 17526460
TI  - Effects of various enteral nutrition solutions on bacterial translocation and
      intestinal morphology during the postoperative period.
AB  - Bacterial translocation is the passage of bacteria or endotoxins from the
      gastrointestinal tract to extraintestinal sites, such as mesenteric lymph nodes,
      liver, spleen, and bloodstream. In this study, the investigators examined the
      effects of various enteral nutrients on bacterial translocation and intestinal
      morphology during the postoperative period. Sixty rats were randomly divided into
      5 groups, each of which included 12 animals; cecal mobilization was performed in
      all groups. Group I rats were fed rat chow and water; group II was given standard
      enteral nutrients; group III, high-energy enteral nutrients; group IV, enteral
      nutrients supplemented with fiber; and group V, immunonutrients. Bacterial
      translocation was detected in mesenteric lymph nodes, spleen, liver, and blood
      cultures. Changes in the terminal ileum were scored from 0 to 4 with the
      morphologic scoring system. Bacterial translocation was predominantly detected in
      mesenteric lymph nodes. Rats fed immunonutrients (group V) showed a significant
      reduction in bacterial translocation compared with other groups. Although minor
      morphologic alterations in the villi were observed in groups IV and V, the
      histologic scores of these groups were not statistically different from the
      scores of control group members. In the present study, investigators evaluated
      the effects of various enteral nutritional solutions on bacterial translocation
      and intestinal morphology during the postoperative period. Enteral diets
      supplemented with arginine, nucleotides, and omega-3 fatty acids were found to
      reduce bacterial translocation. The investigators concluded that this effect
      might be related to improvement in immune function resulting from the use of
      immunonutrients.

PMID- 17526461
TI  - Increased antioxidant capacity in healthy volunteers taking a mixture of oral
      antioxidants versus vitamin C or E supplementation.
AB  - The objectives of this study were (1) to evaluate the capacity of human plasma
      that had been obtained from healthy adult volunteers before and after they
      ingested vitamin E or C to inhibit induced lipoperoxidation in vitro (antioxidant
      capacity of plasma [ACP]), and (2) to compare the efficiency of these vitamins
      with that of a commercial mixture of antioxidant vitamins, cofactors, and
      minerals (MAOx). Seventy-nine healthy individuals between 19 and 23 y of age were
      randomly assigned to 1 of 4 groups. Each received a daily dose of antioxidants
      for 7 d: vitamin C (n=18; 500 mg), vitamin E (n=21; 400 IU), vitamins C and E
      (n=19), or MAOx (n=21; 1.2 g). ACP and plasma malondialdehyde were measured at 4
      and 24 h and 7 d. ACP increased significantly (P<.05) in all 4 groups within 4 h
      of antioxidant intake, and this effect was sustained throughout supplementation.
      Plasma ACP increased significantly over basal values in the group taking MAOx;
      relative increases were 42%, 44%, and 55% at 4 h, 24 h, and 7 d, respectively
      (P<.001). Smaller increases in plasma ACP were observed in the vitamin C group
      (25%, 32%, and 36%) and, specifically, in the vitamin E group (17%, 24%, and 28%)
      (P<.05). The mixture of vitamins and minerals was comparatively more efficient
      than vitamin C or E alone, presumably because MAOx contains various antioxidant
      compounds with different redox potentials, leading to the possible development of
      chain reactions.

PMID- 17526462
TI  - Comparison of tobramycin 0.3%/dexamethasone 0.1% and tobramycin 0.3%/loteprednol
      0.5% in the management of blepharo-keratoconjunctivitis.
AB  - In this clinical trial, investigators compared the effectiveness of 2
      commercially formulated antibiotic/steroid combinations - tobramycin
      0.3%/dexamethasone 0.1% (Tobradex; Alcon, Fort Worth, Tex) and tobramycin
      0.3%/loteprednol 0.5% (Zylet; Bausch & Lomb Inc., Rochester, NY) - for rapidly
      controlling inflammation in patients with blepharo-keratoconjunctivitis.
      Investigators in this randomized, parallel-group, double-masked study examined 40
      eyes of 40 patients with blepharo-keratoconjunctivitis. Patients received
      tobramycin 0.3%/dexamethasone 0.1% or tobramycin 0.3%/loteprednol 0.5% twice
      daily in the test eye, according to the randomization schedule. At baseline, the
      ocular surface was graded on a scale of 3 (extensive) to 0 (minimum) for 4
      components: blepharitis, conjunctivitis, ocular discharge, and corneal punctate
      epithelial keratopathy (PEK). Only those patients with moderate to extensive
      inflammation (cumulative score >6) were included in the study. At follow-up 3 to
      5 d later, the ocular surface was regraded so that treatment response could be
      evaluated. No statistically significant difference was noted between groups in
      pretreatment scores for blepharitis (P=.31), discharge (P=.62), conjunctivitis
      (P=1.0), and PEK (P=.57), or for total ocular inflammation (P=.87). Mean
      posttreatment scores were as follows: total ocular surface scores, 1.8 and 3.4
      (P=.002); blepharitis scores, 0.9 and 1.35 (P=.017); discharge scores, 0.2 and
      0.6 (P=.025); and conjunctivitis scores, 0.15 and 0.6 (P=.013) for
      tobramycin/dexamethasone and tobramycin/loteprednol, respectively. Corneal PEK
      scores were not significantly different between treatments. Tobramycin
      0.3%/dexamethasone 0.1% significantly decreased clinical signs of ocular
      inflammation (ie, blepharitis, discharge, conjunctivitis) and total ocular
      inflammation scores when compared with tobramycin 0.3%/loteprednol 0.5% in
      patients with moderate to severe blepharo-keratoconjunctivitis. The 2 regimens
      also provided comparably rapid decreases in corneal PEK.

PMID- 17526463
TI  - Drug utilization and teratogenicity risk categories during pregnancy.
AB  - A limited number of studies have investigated in detail the use of drugs during
      pregnancy. Researchers in the present study investigated the details of drug
      utilization in pregnant women during the month before pregnancy, at the time that
      they became aware of the pregnancy, and during the first trimester. Face-to-face
      interviews were conducted with 359 pregnant women who were admitted to the fetal
      medicine unit at a university hospital for diagnosis and follow-up. A
      questionnaire was used to document sociodemographic characteristics and details
      of drug use. Drugs were categorized according to the US Food and Drug
      Administration fetal risk classification. Mean maternal age was 29.9+/-5.1 y, and
      mean gestational age was 19.6+/-9.5 wk. Many of the pregnant women studied
      (46.6%) were university graduates, and most (61.9%) had a relatively high annual
      income. Mean gestational age when participants first learned of their pregnancy
      was 39.8+/-16.4 d. One hundred seventeen participants (32.6%) used drugs during
      the month before conception, 54 (15%) at the time when they learned of their
      pregnancy, 180 (50.1%) at the time of the interview, and 289 (80.5%) during the
      first trimester. The percentages of drugs in categories D and X used by these
      subjects were 14%, 13.5%, 2.9%, and 5.9%, respectively. Most of the drugs were
      hormones. The total rate of drug utilization was not high before and during the
      first trimester of pregnancy. A considerable number of women were using drugs
      from the D and X categories; however, these numbers decreased significantly when
      women learned of their pregnancies. Intake of folic acid, vitamins, and iron was
      very low during the preconception period and was not high enough during the first
      trimester; this suggests that particular attention should be paid to the use of
      beneficial "safe" drugs during the preconception and early pregnancy periods.

PMID- 17526464
TI  - Vibration characteristics of grafts for the tympanic membrane.
AB  - Perforation of the tympanic membrane occurs frequently as a result of infection,
      external trauma, and high-level impulsive sound pressure, such as that associated
      with an explosion. Many different surgical techniques can be used to repair the
      tympanic membrane and ossicles. Clinical operations such as tympanoplasty are
      undertaken to repair the damaged tympanic membrane and ossicles, thus improving
      hearing and reducing the chance of infection. The membrane is repaired or
      replaced with the use of graft materials, either from the patient's body or from
      artificial sources. The selection of graft material is very important because, as
      much as possible, it must exhibit the same dynamic behavior as the natural
      membrane. To compare various allograft materials, investigators developed a model
      of the ear on which different graft materials can be replaced. Three different
      membrane materials - irradiated allograft dura (Tutoplast Dura; IOP Inc., Costa
      Mesa, Calif), irradiated allograft fascia lata (Tutoplast Fascia Lata; IOP Inc.),
      and irradiated allograft fascia temporalis (Tutoplast Fascia Temporalis; IOP
      Inc.) - were used. Vibration responses of these membrane materials produced by
      defined sound signals with different frequencies were recorded by a small strain
      gauge; the spectra of sound for various corresponding input signals were
      recorded, and the results were compared with those of the sample graft material.
      Tutoplast Fascia Lata accomplished the best dynamic performance in vitro.
      Additional clinical and experimental data are needed, however, to determine which
      of these materials provides the best audiological and clinical performance.

PMID- 17526465
TI  - Effects of melatonin on Candida sepsis in an experimental rat model.
AB  - As an immunomodulator, melatonin reportedly exhibits protective effects in severe
      sepsis/shock induced by bacterial lipopolysaccharides in animal models. The
      present study was conducted to evaluate the possible protective effects of
      melatonin against experimental Candida sepsis in rats. A total of 40 adult male
      Wistar rats were randomly assigned to 4 groups: control, melatonin-treated
      control, septic, and melatonin-treated septic. Melatonin (200 microg/kg/d,
      intraperitoneally) injections were begun a week prior to sepsis induction and
      were continued daily for 3 wk until the end of the study. Cyclophosphamide was
      administered to animals in all groups as an immunosuppressive agent as a single
      dose 4 d prior to yeast inoculation. To cause sepsis, the Candida albicans (ATCC
      10259) strain was administered intravenously. Amphotericin B was given as an
      antimycotic therapeutic agent as a single dose to septic rats. Plasma levels of
      interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), vascular cell
      adhesion molecule-1, and E-selectin were measured on the first and 15th days of
      sepsis. IL-6, TNF-alpha, vascular cell adhesion molecule-1, and E-selectin levels
      of septic rats were higher than those of controls. Melatonin reduced IL-6 levels
      and shortened time to improvement in animals with Candida sepsis. Levels of TNF
      alpha and adhesion molecules in melatonin-treated septic rats were decreased
      compared with those in septic rats, but this difference was not statistically
      significant. In light of the current results, investigators conclude that
      melatonin may have therapeutic benefits in Candida sepsis and in classic
      antimycotic treatment because of its immune regulatory effects.

PMID- 17526466
TI  - Fourteen cases of neonatal ultrahyperpyrexia syndrome induced by improper care.
AB  - This report describes the clinical characteristics, treatment, and pathologic
      mechanisms of neonatal ultrahyperpyrexia syndrome induced by improper care.
      Clinical data on 14 cases of neonatal ultrahyperpyrexia syndrome induced by
      improper care were retrospectively analyzed. All 14 neonates had become comatose
      with ultrahyperpyrexia or hyperpyrexia; 8 of these patients twitched, 12 had high
      muscular tension, 2 exhibited low muscle tone, and 9 had respiratory dysfunction.
      Computed tomography revealed a patched, low dense shadow in the frontal and
      parietal lobes of the cerebral cortex in 9 patients; local cerebral hemorrhage
      occurred in 3 cases, and subarachnoid hemorrhage was reported in 2. After
      systematic treatment was provided, 13 neonates survived, but 1 died. Dysfunction
      of the neural, respiratory, and circulatory systems was the main pathologic
      mechanism noted in these cases of neonatal ultrahyperpyrexia syndrome induced by
      improper care. Early treatment, acute hypothermia, and supplemental fluids are
      the keys to successful therapy.

PMID- 17526467
TI  - Can hyperbaric oxygen be used as adjunctive heart failure therapy through the
      induction of endogenous heat shock proteins?
AB  - Heart failure (HF) is a chronic condition that is expected to increase in
      incidence along with increased life expectancy and an aging population. As the
      incidence of HF increases, the cost to national healthcare budgets is expected to
      run into the billions. The costs of lost productivity and increased social
      reliance on state support must also be considered. Recently, acute myocardial
      infarction (AMI) has come to be seen as the major contributing factor to HF.
      Although thrombolysis may restore coronary perfusion after an AMI, it may also
      introduce ischemic reperfusion injury (IRI). In an attempt to ameliorate
      sustained protein damage caused by IRI, endogenous chaperone proteins known as
      heat shock proteins (HSPs) are induced as a consequence of the stress of IRI.
      Recently, hyperbaric oxygen has been shown to induce the production of HSPs in
      noncardiac tissue, with a resultant protective effect. This current opinion
      review article suggests a possible role for hyperbaric oxygen, as a
      technologically modern drug, in augmenting the induction of endogenous HSPs to
      repair and improve the function of failing hearts that have been damaged by AMI
      and IRI. In addition, this simple, safe, noninvasive drug may prove useful in
      easing the economic burden of HF on already overextended health resources.

PMID- 17526468
TI  - Morphologic and quantitative analyses of leukocytes in patients with multiple
      system trauma.
AB  - Multiple system trauma can occur in accidents, natural disasters, and deliberate
      attacks, and vital areas of the body, such as the head, chest, and abdomen, may
      be affected. Investigators in the present study sought to examine morphologic and
      morphometric alterations of leukocyte responses in patients with multiple trauma
      during the first 4 h after a traumatic event. Venous blood samples were drawn
      from 51 patients, 30 male and 21 female, aged 16 to 59 y. The number of
      leukocytes increased significantly in all patients, but no significant
      differences were noted between the male and female groups. Complete blood counts
      revealed normal ratios of leukocyte types. It is suggested that in patients who
      have experienced multiple trauma, aggressive antibiotic therapy should be
      initiated to prevent posttraumatic infection and to protect against secondary
      organ failure.

PMID- 17526469
TI  - Appropriate intervention strategies for weight gain induced by olanzapine: a
      randomized controlled study.
AB  - Weight gain induced by antipsychotics is the second most frequently given reason
      for noncompliance with pharmacologic therapy; excessive sedative effects rank
      first, with extrapyramidal side effects ranking third. Frequently, weight gain
      leads to inconsistent pharmacologic treatment; this exposes patients to the risk
      of recurrent symptoms. In fact, one of the key contributors to good clinical
      outcomes in schizophrenic patients is compliance with pharmacologic treatment.
      The goals of this study were to evaluate weight gain in a group of patients
      treated with olanzapine, diet modifications, and moderate physical activity and
      to compare the findings with those from a second group of patients who were given
      only olanzapine treatment. For 8 wk, investigators followed 2 groups of patients
      suffering from schizophrenia and hypomania in bipolar disorder, according to the
      nosographic criteria of The Diagnostic and Statistical Manual of Mental
      Disorders, Fourth Edition (DSM-IV). The first group (A) of 18 patients (9 female,
      9 male) affected by manic episodes in bipolar disorder received olanzapine (10-20
      mg/d), jogged lightly for 30 min 3 times a week, and complied with a diet that
      consisted of 500 kcal/d less than usual. The second group (B) of 10 patients (4
      female, 6 male) with schizophrenia received only olanzapine (10-20 mg/d). All
      patients from both groups were weighed at the beginning of the observation period
      and weekly thereafter for 2 mo. After 2 mo of observation, group A showed a mean
      weight gain of 1.47 kg, whereas group B exhibited a mean weight gain of 3.5 kg;
      the difference between the 2 groups was almost 2 kg (P<.005). Group A showed a
      statistically significant reduction in weight gain compared with group B, clearly
      demonstrating the effectiveness of moderate physical activity and diet therapy in
      reducing weight gain in atypical antipsychotic treatment. Therefore, patient
      weight and body mass index must be monitored during the first weeks of
      antipsychotic treatment, with the goals of avoiding significant weight gain and
      treatment interruption.

PMID- 17526470
TI  - Attitudes of physiotherapists and physiotherapy students toward euthanasia: a
      comparative study.
AB  - This interventional study was undertaken to assess the impact of physiotherapy
      education on the knowledge and attitudes of physiotherapists (PTs) and
      physiotherapy students (PSs) toward euthanasia. The study, which was conducted
      during the period between 2004 and 2005, included a total of 494 participants
      (311 PTs; 183 PSs) aged 18 to 52 y from the western and central portions of
      Turkey, who responded to a self-report questionnaire (response rate, 96.4%) that
      was based on data from the literature. Results indicated that PTs (48.9%) were
      more likely to approve of euthanasia than PSs (38.3%) (P<.05). The legalization
      of euthanasia was favored by 43.7% of PTs, compared with 29.5% of PSs (P<.05). On
      the other hand, PTs and PSs expressed similar views regarding euthanasia,
      including reasons for accepting or opposing euthanasia and acceptable conditions
      for its use (P>.05). Overall results showed that sex and age had no effect on
      whether euthanasia was accepted (P>.05) religiousness was found to have the
      greatest effect on attitudes toward euthanasia (P<.05). The findings of the
      current study suggest that (1) the attitudes of PTs are different from those of
      PSs, and (2) the Islamic point of view has a negative impact on the attitudes of
      PTs and PSs toward euthanasia.

PMID- 17526471
TI  - Telmisartan improves lipid metabolism and adiponectin production but does not
      affect glycemic control in hypertensive patients with type 2 diabetes.
AB  - Angiotensin II receptor blockers as a class are reported to act as insulin
      sensitizers. Of these, telmisartan has been shown to have additional unique
      peroxisome proliferator-activated receptor-gamma-mediated, insulin-sensitizing
      properties. In this study, investigators explored the effects of telmisartan on
      glycemic control and lipid metabolism in hypertensive patients with type 2
      diabetes who had switched to telmisartan from another angiotensin II receptor
      blocker. The study subjects were 42 hypertensive outpatients with type 2 diabetes
      who were being treated with candesartan 8 mg/d and who agreed to switch to
      treatment with telmisartan 40 mg/d. Relevant laboratory variables were measured 6
      mo before treatment switching, at the time of switching, and 6 mo after
      switching. No significant differences were noted in blood pressure, body mass
      index, or glycosylated hemoglobin among subjects before and after therapy was
      switched. No adverse reactions such as edema or hepatic toxicity were noted. No
      significant changes in fasting plasma glucose, fasting insulin, HOMA-R (insulin
      resistance as measured by the homeostasis model), preheparin lipoprotein lipase
      mass, high-density lipoprotein cholesterol, and free fatty acids were noted.
      Triglyceride levels were significantly decreased, however, and adiponectin levels
      were significantly increased (8.1+/-3.1 microg/mL at switching; 8.6+/-3.0
      microg/mL 6 mo after switching; P<.01) after the switch to telmisartan therapy.
      Study results show that telmisartan did not affect glycemic control, but it
      improved lipid metabolism and adiponectin production in patients with type 2
      diabetes, suggesting that AT(1)-receptor antagonism and selective peroxisome
      proliferator-activated receptor-gamma activation by telmisartan combine to
      account for observed effects on lipid metabolism and adiponectin production.

PMID- 17526472
TI  - A controlled trial of glutamine effects on bone healing.
AB  - Glutamine is considered a nonessential amino acid, but it may be conditionally
      essential in patients with catabolic conditions. For centuries, researchers have
      looked for ways to promote and accelerate fracture healing. This controlled
      animal study examines the effects of glutamine on fracture healing. The left
      tibias of 10 standardized albino rats were broken at the distal third to produce
      a closed fracture. L-glutamine/L-alanyl solution (2.0 mL/kg) was administered
      through the tail veins of half the rats for the first 7 d, and physiologic serum
      alone was given to the control group. On the 21st day, all rats were euthanized
      and their left legs removed; after histologic observation, the tibias were
      examined under light microscopy. In the glutamine-injected group, development of
      primary callus was quicker and more regular than in the control group. The
      control group produced insufficient fibrous callus, and the glutamine group
      attained formed cartilaginous callus. Glutamine was noted to have positive
      effects on healing of traumatically fractured bone through attainment of positive
      nitrogen balance. This effect was minimal in enhancing the quality of fracture
      healing under conditions of stress, but some effect was noted on the speed of
      healing. Further research is needed in this area.

PMID- 17526473
TI  - Initial clinical experience with the trabecular micro-bypass stent in patients
      with glaucoma.
AB  - This study was undertaken to evaluate the efficiency of a trabecular micro-bypass
      stent designed to allow direct aqueous drainage from the anterior chamber into
      Schlemm's canal in patients with glaucoma. In this prospective case series of 6
      patients with open-angle glaucoma, the microstent was inserted ab interno under
      local anesthesia in an ophthalmic operating room. Patients were seen
      postoperatively at 1 to 2 d, 1 wk, and 1, 2, 6, and 12 mo. All stents were
      successfully placed within Schlemm's canal. Mean intraocular pressure (IOP) at
      preoperative baseline was 20.2+/-6.3 mm Hg (range, 14-31 mm Hg). Mean IOP
      decreased during the immediate postoperative period to approximately 12 to 13 mm
      Hg and was stabilized at 14 to 15 mm Hg with reduction of medication throughout 1
      y of follow-up. No major complications occurred. According to observations
      reported in this feasibility study, the microstent was effective in reducing IOP
      and in decreasing the number of glaucoma medications required to control IOP.
      Implantation procedures were safe, and stents remained in place throughout the
      follow-up period. None of the complications traditionally associated with
      filtering surgery were reported. Further research on this stent in a larger group
      of patients is needed to assess its role in glaucoma therapy.

PMID- 17526474
TI  - Effects of spinal anesthesia and laryngeal mask anesthesia on mood states during
      hemorrhoidectomy.
AB  - The present study was undertaken to compare the effects of laryngeal mask
      anesthesia (LMA) and spinal anesthesia on mood states in patients undergoing
      hemorrhoidectomy. A total of 46 patients who underwent hemorrhoidectomy for grade
      III and IV hemorrhoids were included in this study. LMA with fentanyl plus
      propofol was given to 23 patients, and spinal anesthesia with bupivacaine was
      administered to 23 patients. Mood changes were assessed preoperatively and 2 h
      postoperatively with the Profile of Mood States (POMS), which consists of 65
      questions that are designed to measure 6 identifiable mood states (tension,
      depression, anger, vigor, fatigue, and confusion). No significant differences
      were noted between the 2 groups in terms of baseline POMS global and subscale
      scores, except for scores regarding vigor. No significant mood changes were
      observed after hemorrhoidectomy in patients who were given LMA; however, an
      increase in total POMS score was reported in patients given spinal anesthesia.
      These findings suggest that mood score is affected by spinal anesthesia but not
      by LMA in patients who are about to undergo hemorrhoidectomy.

PMID- 17526475
TI  - The left anterior descending artery arising from the right sinus of Valsalva: a
      case report.
AB  - Coronary artery anomalies occur in less than 1% of patients who undergo coronary
      angiography and they account for 1% to 2% of all cases of congenital heart
      disease. The most commonly encountered anomaly, the circumflex artery originating
      from the right coronary artery or the right sinus of Valsalva, is usually well
      tolerated. The patient in the case presented here was found to have a left
      anterior descending artery arising from the right sinus of Valsalva - a situation
      that is very rarely encountered.

PMID- 17526476
TI  - Acute effect of methylphenidate on QT interval duration and dispersion in
      children with attention deficit hyperactivity disorder.
AB  - Among childhood psychiatric disorders, attention deficit hyperactivity disorder
      (ADHD) is of greatest interest to practitioners. Methylphenidate (MPH) is a drug
      that is widely used in the treatment of children in whom ADHD has been diagnosed.
      Although this treatment has been used for years, its effects on the heart remain
      the subject of debate. The QT interval comprises the ventricular activation and
      recovery periods as seen on electrocardiogram (ECG). The acute effect of MPH on
      QT interval dispersion is unknown. Researchers in the present study sought to
      investigate the acute effects of MPH on QT interval as seen on ECG. A total of 25
      patients with ADHD (mean age, 9.4+/-2.1 y) who were treated with MPH were
      enrolled in the study. Twelve-lead derivation ECGs were taken before and 2 h
      after administration of 10 mg of MPH. Maximum QT interval, minimum QT interval,
      and interval durations were measured, and QT dispersion was calculated, for each
      ECG. QT dispersion measured after medication administration decreased
      significantly from 59.6+/-16.3 ms to 50.8+/-10.9 ms (P=.016); corrected QT
      dispersion decreased significantly from 70.9+/-17.6 ms to 61.3+/-13.3 ms
      (P=.011). Maximum QT interval duration decreased from 73.7+/-21.8 ms to 361.8+/
      29.0 ms (P=.006); minimum QT interval duration rose from 317.0+/-23.3 ms to
      322.3+/-21.6 ms (P=.312). In conclusion, the findings of this study show that MPH
      reduces QT dispersion during the acute period shortly after its administration.

PMID- 17526477
TI  - Modulation of prostaglandin activity, part 1: prostaglandin inhibition in the
      management of nonrheumatologic diseases: immunologic and hematologic aspects.
AB  - Prostaglandins (PGs) are active biologic substances that are involved in a wide
      range of physiologic processes; when their production is out of balance, they are
      factors in the pathogenesis of illness. Modulation of PGs by inhibition or
      stimulation is promising for the management of various conditions. PG inhibitors
      are widely used to relieve pain and inflammation in patients with rheumatologic
      disease. Interest in the use of PG inhibitors to prevent cancer and
      cardiovascular events is growing. More than 27 y ago, investigators found that PG
      depresses antibody production in vivo; reduces serum iron, hemoglobin, and
      leukoid series in bone marrow during acute and chronic blood loss; reduces
      albumin during antigenic stimulation; suppresses hypercalcemia after bleeding;
      and reduces fasting blood sugar and hyperglycemia after ether anesthesia and
      bleeding. Chronic conditions that produce large quantities of PGs are associated
      with immunosuppression and secondary anemia. Investigators in the present study
      hypothesized (1) that the overproduction of PGs is responsible for
      immunosuppression and secondary anemia in conditions associated with increased PG
      synthesis, such as pathologic inflammation, malignancy, trauma, and injury, and
      (2) that PG inhibitors reverse immunosuppression and secondary anemia, thereby
      enhancing the immune response. This is supported by many reports that show the
      immunosuppressive effects of PGs and their role in the immunosuppression
      associated with pathologic inflammation, burns, trauma, and tumors. Inhibition of
      PGs can be achieved through the use of synthetic medicines and natural products.
      This article reviews the effects of PGs and inhibition of increased synthesis of
      PGs on the lymphoid system, hematologic indices, and bone marrow elements in
      trauma, injury, burns, and tumors. The Medline database (1966-2006) was used in
      this study. Investigators in the present study and others have provided evidence
      that shows the involvement of PGs in immunosuppression and secondary anemia, as
      well as the efficacy of inhibited overproduction of PGs in many pathologic
      conditions other than rheumatologic disease.

PMID- 17526478
TI  - Progress in dosimetry of neutrons and light nuclei.

PMID- 17526479
TI  - Dosimetry at an interim storage for spent nuclear fuel.
AB  - The Czech nuclear power plant Dukovany started its operation in 1985. All fuel
      spent from 1985 up to the end of 2005 is stored at a dry interim storage, which
      was designed for 60 CASTOR-440/84 casks. Each of these casks can accommodate 84
      fuel assemblies from VVER 440 reactors. Neutron-photon mixed fields around the
      casks were characterized in terms of ambient dose equivalent measured by standard
      area dosemeters. Except this, neutron spectra were measured by means of a Bonner
      sphere spectrometer, and the measured spectra were used to derive the
      corresponding ambient dose equivalent due to neutrons.

PMID- 17526480
TI  - Detection system built from commercial integrated circuits for real-time
      measurement of radiation dose and quality using the variance method.
AB  - A small, specialised amplifier using commercial integrated circuits (ICs) was
      developed to measure radiation dose and quality in real time using a
      microdosimetric ion chamber and the variance method. The charges from a
      microdosimetric ion chamber, operated in the current mode, were repeatedly
      collected for a fixed period of time for 20 cycles of 100 integrations, and
      processed by this specialised amplifier to produce signal pulse heights between 0
      and 10 V. These signals were recorded by a multi-channel analyser coupled to a
      computer. FORTRAN programs were written to calculate the dose and dose variance.
      The dose variance produced in the ion chamber is a microdosimetric measure of
      radiation quality. Benchmark measurements of different brands of ICs were
      conducted. Results demonstrate that this specialised amplifier is capable of
      distinguishing differences of radiation quality in various high-dose-rate
      radiation fields including X rays, gamma rays and mixed neutron-gamma radiation
      from the research reactor at Texas A&M University Nuclear Science Center.

PMID- 17526481
TI  - Photon contribution to ambient dose equivalent H(10) in the wide-spectrum neutron
      reference fields of the IRSN.
AB  - The photon contribution to ambient dose equivalent in several wide-spectrum
      reference neutrons fields of the Institute for Radiological Protection and
      Nuclear Safety were measured using a Geiger-Muller counter. For the investigated
      fields, the ratio of photon to neutron ambient dose equivalent ranged between
      0.03 and 0.20. The results show that the Geiger-Muller tube is a versatile
      instrument for dosimetry in mixed photon-neutron fields if sufficient information
      for the calculation of corrections is available.

PMID- 17526482
TI  - Measurement of natural radioactivity and dose rate assessment of terrestrial
      gamma radiation in the soil of southern Punjab, Pakistan.
AB  - Activity concentrations of (226)Ra, (232)Th, (40)K and (137)Cs in soil samples
      collected from the most populous area of southern Punjab of Pakistan have been
      measured by gamma-ray spectrometry. The measured activity concentrations for
      these radionuclides are compared with the reported data from different other
      countries and it is found that measured activity concentrations are comparable
      with the worldwide measured average values reported by the UNSCEAR. Subsequently
      assessed radiological effects show that the mean radium equivalent activity
      (Ra(eq)) is 96.7 +/- 15.2 Bq kg(-1) and air absorbed dose rate (D) is 46.1 +/-
      7.3 nGy h(-1). The values of internal and external radiation hazard indices are
      found to be less than unity. The annual effective radiation dose is calculated to
      be 0.28 +/- 0.05 mSv, which is well below the limit of 1.0 mSv y(-1) recommended
      by the International Commission on Radiological Protection, for the general
      public.

PMID- 17526483
TI  - First intercomparison of Tn-Rn discriminative measurements in China.
AB  - The intercomparison measurements with Tn-Rn discriminative monitor were conducted
      at the Radon Laboratory of Nanhua University. The intercomparison results
      indicates that the Tn-Rn discrimination of most monitors (including the solid
      state nuclear track detector of participant A and participant B, continuous
      monitors of RAD7 and RTM2100) keeps well in a wide range of the ratio of Tn to
      Rn. There are great differences of Tn measurement results among RAD7, RTM2100 and
      reference instrument. The discussion on the reason of these differences reveals
      the necessity of improvement on monitor calibration, Tn source make and the
      necessity of more international intercomparisons.

PMID- 17526484
TI  - Elastic neutron scattering studies at 96 MeV for transmutation.
AB  - Elastic neutron scattering from (12)C, (14)N, (16)O, (28)Si, (40)Ca, (56)Fe,
      (89)Y and (208)Pb has been studied at 96 MeV in the10-70 degrees interval, using
      the SCANDAL (SCAttered Nucleon Detection AssembLy) facility. The results for
      (12)C and (208)Pb have recently been published, while the data on the other
      nuclei are under analysis. The achieved energy resolution, 3.7 MeV, is about an
      order of magnitude better than for any previous experiment above 65 MeV incident
      energy. A novel method for normalisation of the absolute scale of the cross
      section has been used. The estimated normalisation uncertainty, 3%, is
      unprecedented for a neutron-induced differential cross section measurement on a
      nuclear target. Elastic neutron scattering is of utmost importance for a vast
      number of applications. Besides its fundamental importance as a laboratory for
      tests of isospin dependence in the nucleon-nucleon, and nucleon-nucleus,
      interaction, knowledge of the optical potentials derived from elastic scattering
      come into play in virtually every application where a detailed understanding of
      nuclear processes is important. Applications for these measurements are dose
      effects due to fast neutrons, including fast neutron therapy, as well as nuclear
      waste incineration and single event upsets in electronics. The results at light
      nuclei of medical relevance ((12)C, (14)N and (16)O) are presented separately. In
      the present contribution, results on the heavier nuclei are presented, among
      which several are of relevance to shielding of fast neutrons.

PMID- 17526485
TI  - Natural radioactivity measurements in rock samples of Cuihua Mountain National
      Geological Park, China.
AB  - The concentrations of the natural radionuclides namely 40K, 232Th and 226Ra in
      rock samples collected from Cuihua Mountain National Geological Park of China
      have been determined using a NaI(Tl) detector. The concentrations of 226Ra, 232Th
      and 40K in the studied rock samples range from 10.7 to 34.8, 19.9 to 53.6 and
      642.7 to 1609.9 Bq kg(-1) with an average of 20.4, 30.1 and 1009.5 Bq kg(-1),
      respectively. The concentrations of these radionuclides are compared with the
      typical world values. To evaluate the radiological hazard of the natural
      radioactivity, the radium equivalent activity, the air absorbed dose rate, the
      annual effective dose rate, the representative level index and the values of both
      external and internal hazard indices were evaluated and compared with the
      internationally approved values. The radium equivalent activity values of all
      rock samples are lower than the limit of 370 Bq kg(-1). The values of H ex and H
      in are less than unity. The mean outdoor air absorbed dose rate is 69.7 nGy h(
      1), and the corresponding outdoor effective dose rate is 0.086 mSv y(-1).

PMID- 17526486
TI  - Functional links between the fusion peptide-proximal polar segment and membrane
      proximal region of human immunodeficiency virus gp41 in distinct phases of
      membrane fusion.
AB  - The binding of CD4 and chemokine receptors to the gp120 attachment glycoprotein
      of human immunodeficiency virus triggers refolding of the associated gp41 fusion
      glycoprotein into a trimer of hairpins with a 6-helix bundle (6HB) core. These
      events lead to membrane fusion and viral entry. Here, we examined the functions
      of the fusion peptide-proximal polar segment and membrane-proximal Trp-rich
      region (MPR), which are exterior to the 6HB. Alanine substitution of Trp(666),
      Trp(672), Phe(673), and Ile(675) in the MPR reduced entry by up to 120-fold
      without affecting gp120-gp41 association or cell-cell fusion. The L537A polar
      segment mutation led to the loss of gp120 from the gp120-gp41 complex, reduced
      entry by approximately 10-fold, but did not affect cell-cell fusion. Simultaneous
      Ala substitution of Leu(537) with Trp(666), Trp(672), Phe(673), or Ile(675)
      abolished entry with 50-80% reductions in cell-cell fusion. gp120-gp41 complexes
      of fusion-defective double mutants were resistant to soluble CD4-induced shedding
      of gp120, suggesting that their ability to undergo receptor-induced
      conformational changes was compromised. Consistent with this idea, a
      representative mutation, L537A/W666A, led to an approximately 80% reduction in
      lipophilic fluorescent dye transfer between gp120-gp41-expressing cells and
      receptor-expressing targets, indicating a block prior to the lipid-mixing phase.
      The L537A/W666A double mutation increased the chymotrypsin sensitivity of the
      polar segment in a trimer of hairpins model, comprising the 6HB core, the polar
      segment, and MPR linked N-terminally to maltose-binding protein. The data
      indicate that the polar segment and MPR of gp41 act synergistically in forming a
      fusion-competent gp120-gp41 complex and in stabilizing the membrane-interactive
      end of the trimer of hairpins.

PMID- 17526487
TI  - Transcriptional regulation of the bovine leukemia virus promoter by the cyclic
      AMP-response element modulator tau isoform.
AB  - Bovine leukemia virus (BLV) expression is controlled at the transcriptional level
      through three Tax(BLV)-responsive elements (TxREs) responsive to the viral
      transactivator Tax(BLV). The cAMP-responsive element (CRE)-binding protein (CREB)
      has been shown to interact with CRE-like sequences present in the middle of each
      of these TxREs and to play critical transcriptional roles in both basal and
      Tax(BLV)-transactivated BLV promoter activity. In this study, we have
      investigated the potential involvement of the cAMP-response element modulator
      (CREM) in BLV transcriptional regulation, and we have demonstrated that CREM
      proteins were expressed in BLV-infected cells and bound to the three BLV TxREs in
      vitro. Chromatin immunoprecipitation assays using BLV-infected cell lines
      demonstrated in the context of chromatin that CREM proteins were recruited to the
      BLV promoter TxRE region in vivo. Functional studies, in the absence of Tax(BLV),
      indicated that ectopic CREMtau protein had a CRE-dependent stimulatory effect on
      BLV promoter transcriptional activity. Cross-link of the B-cell receptor
      potentiated CREMtau transactivation of the viral promoter. Further experiments
      supported the notion that this potentiation involved CREMtau Ser-117
      phosphorylation and recruitment of CBP/p300 to the BLV promoter. Although CREB
      and Tax(BLV) synergistically transactivated the BLV promoter, CREMtau repressed
      this Tax(BLV)/CREB synergism, suggesting that a modulation of the level of
      Tax(BLV) transactivation through opposite actions of CREB and CREMtau could
      facilitate immune escape and allow tumor development.

PMID- 17526488
TI  - Interferon regulatory factor 3 is regulated by a dual phosphorylation-dependent
      switch.
AB  - The transcription factor interferon regulatory factor 3 (IRF-3) regulates genes
      in the innate immune response. IRF-3 is activated through phosphorylation by the
      kinases IKK epsilon and/or TBK1. Phosphorylation results in IRF-3 dimerization
      and removal of an autoinhibitory structure to allow interaction with the
      coactivators CBP/p300. The precise role of the different phosphorylation sites
      has remained controversial. Using purified proteins we show that TBK1 can
      directly phosphorylate full-length IRF-3 in vitro. Phosphorylation at residues in
      site 2 (Ser(396)-Ser(405)) alleviates autoinhibition to allow interaction with
      CBP (CREB-binding protein) and facilitates phosphorylation at site 1 (Ser(385) or
      Ser(386)). Phosphorylation at site 1 is, in turn, required for IRF-3
      dimerization. The data support a two-step phosphorylation model for IRF-3
      activation mediated by TBK1.

PMID- 17526489
TI  - Functional sequestration of transcription factor activity by repetitive DNA.
AB  - Higher eukaryote genomes contain repetitive DNAs, often concentrated in
      transcriptionally inactive heterochromatin. Although repetitive DNAs are not
      typically considered as regulatory elements that directly affect transcription,
      they can contain binding sites for some transcription factors. Here, we
      demonstrate that binding of the transcription factor CCAAT/enhancer-binding
      protein alpha (C/EBPalpha) to the mouse major alpha-satellite repetitive DNA
      sequesters C/EBPalpha in the transcriptionally inert pericentromeric
      heterochromatin. We find that this sequestration reduces the transcriptional
      capacity of C/EBPalpha. Functional sequestration of C/EBPalpha was demonstrated
      by experimentally reducing C/EBPalpha binding to the major alpha-satellite DNA,
      which elevated the concentration of C/EBPalpha in the non-heterochromatic
      subcompartment of the cell nucleus. The reduction in C/EBPalpha binding to alpha
      satellite DNA was induced by the co-expression of the transcription factor Pit-1,
      which removes C/EBPalpha from the heterochromatic compartment, and by the
      introduction of an altered-specificity mutation into C/EBPalpha that reduces
      binding to alpha-satellite DNA but permits normal binding to sites in some gene
      promoters. In both cases the loss of alpha-satellite DNA binding coincided with
      an elevation in the binding of C/EBPalpha to a promoter and an increased
      transcriptional output from that promoter. Thus, the binding of C/EBPalpha to
      this highly repetitive DNA reduced the amount of C/EBPalpha available for binding
      to and regulation of this promoter. The functional sequestration of some
      transcription factors through binding to repetitive DNAs may represent an
      underappreciated mechanism controlling transcription output.

PMID- 17526490
TI  - A critical role for IkappaB kinase beta in metallothionein-1 expression and
      protection against arsenic toxicity.
AB  - Arsenic is a widespread environmental toxic agent that has been shown to cause
      diverse tissue and cell damage and at the same time to be an effective anti
      cancer therapeutic agent. The objective of this study is to explore the signaling
      mechanisms involved in arsenic toxicity. We show that the IkappaB kinase beta
      (IKKbeta) plays a crucial role in protecting cells from arsenic toxicity.
      Ikkbeta(-)(/)(-) mouse 3T3 fibroblasts have decreased expression of antioxidant
      genes, such as metallothionein 1 (Mt1). In contrast to wild type and IKKbeta
      reconstituted Ikkbeta(-)(/)(-) cells, IKKbeta-null cells display a marked
      increase in arsenic-induced reactive oxygen species (ROS) accumulation, which
      leads to activation of the MKK4-c-Jun NH(2)-terminal kinase (JNK) pathway, c-Jun
      phosphorylation, and apoptosis. Pretreatment with the antioxidant N
      acetylcysteine (NAC) and expression of MT1 in the Ikkbeta(-)(/)(-) cells
      prevented JNK activation; moreover, NAC pretreatment, MT1 expression, MKK4
      ablation, and JNK inhibition all protected cells from death induced by arsenic.
      Our data show that two signaling pathways appear to be important for modulating
      arsenic toxicity. First, the IKK-NF-kappaB pathway is crucial for maintaining
      cellular metallothionein-1 levels to counteract ROS accumulation, and second,
      when this pathway fails, excessive ROS leads to activation of the MKK4-JNK
      pathway, resulting in apoptosis.

PMID- 17526491
TI  - Targeting and retention of type 1 ryanodine receptors to the endoplasmic
      reticulum.
AB  - Most ryanodine receptors and their relatives, inositol 1,4,5-trisphosphate
      receptors, are expressed in the sarcoplasmic or endoplasmic reticulum (ER), where
      they mediate Ca(2+) release. We expressed fragments of ryanodine receptor type 1
      (RyR1) in COS cells alone or fused to intercellular adhesion molecule-1 (ICAM-1),
      each tagged with yellow fluorescent protein, and used confocal imaging and
      glycoprotein analysis to identify the determinants of ER targeting and retention.
      Single transmembrane domains (TMD) of RyR1 taken from the first (TMD1-TMD2) or
      last (TMD5-TMD6) pair were expressed in the ER membrane. TMD3-TMD4 was expressed
      in the outer mitochondrial membrane. The TMD outer pairs (TMD1-TMD2 and TMD5
      TMD6) retained ICAM-1, a plasma membrane-targeted protein, within the ER
      membrane. TMD1 alone provided a strong ER retention signal and TMD6 a weaker
      signal, but the other single TMD were unable to retain ICAM-1 in the ER. We
      conclude that TMD1 provides the first and sufficient signal for ER targeting of
      RyR1. The TMD outer pairs include redundant ER retention signals, with TMD1
      providing the strongest signal.

PMID- 17526492
TI  - Selenoprotein H is a redox-sensing high mobility group family DNA-binding protein
      that up-regulates genes involved in glutathione synthesis and phase II
      detoxification.
AB  - Selenoprotein H is a recently identified member of the selenoprotein family whose
      function is not fully known. Previous studies from our laboratory and others
      showed that Drosophila melanogaster selenoprotein H is essential for viability
      and antioxidant defense. In this study we investigated the function of human
      selenoprotein H in murine hippocampal HT22 cells engineered to stably overexpress
      the protein. After treatment of cells with L-buthionine-(S,R)-sulfoximine to
      deplete glutathione, selenoprotein H-overexpressing cells exhibited higher levels
      of total glutathione, total antioxidant capacities, and glutathione peroxidase
      enzymatic activity than did vector control cells. Overexpression of selenoprotein
      H also up-regulated the mRNA levels of endogenous selenoprotein H,
      glutamylcysteine synthetase heavy and light chains, and glutathione S
      transferases Alpha 2, Alpha 4, and Omega 1. The amino acid sequence of
      selenoprotein H contains four putative nuclear localization sequences and an AT
      hook motif, a small DNA-binding domain first identified in high mobility group
      proteins. Chromatin immunoprecipitation using a green fluorescent protein
      selenoprotein H fusion revealed binding to sequences containing heat shock and/or
      stress response elements. Thus, selenoprotein H is a redox-responsive DNA-binding
      protein of the AT-hook family and functions in regulating expression levels of
      genes involved in de novo glutathione synthesis and phase II detoxification in
      response to redox status.

PMID- 17526493
TI  - The Mre11-Rad50-Nbs1 complex acts both upstream and downstream of ataxia
      telangiectasia mutated and Rad3-related protein (ATR) to regulate the S-phase
      checkpoint following UV treatment.
AB  - The Mre11-Rad50-Nbs1 (MRN) complex is required for mediating the S-phase
      checkpoint following UV treatment, but the underlying mechanism is not clear.
      Here we demonstrate that at least two mechanisms are involved in regulating the S
      phase checkpoint in an MRN-dependent manner following UV treatment. First, when
      replication forks are stalled, MRN is required upstream of ataxia telangiectasia
      mutated and Rad3-related protein (ATR) to facilitate ATR activation in a
      substrate and dosage-dependent manner. In particular, MRN is required for ATR
      directed phosphorylation of RPA2, a critical event in mediating the S-phase
      checkpoint following UV treatment. Second, MRN is a downstream substrate of ATR.
      Nbs1 is phosphorylated by ATR at Ser-343 when replication forks are stalled, and
      this phosphorylation event is also important for down-regulating DNA replication
      following UV treatment. Moreover, we demonstrate that MRN and ATR/ATR-interacting
      protein (TRIP) interact with each other, and the forkhead-associated/breast
      cancer C-terminal domains (FHA/BRCT) of Nbs1 play a significant role in mediating
      this interaction. Mutations in the FHA/BRCT domains do not prevent ATR activation
      but specifically impair ATR-mediated Nbs1 phosphorylation at Ser-343, which
      results in a defect in the S-phase checkpoint. These data suggest that MRN plays
      critical roles both upstream and downstream of ATR to regulate the S-phase
      checkpoint when replication forks are stalled.

PMID- 17526494
TI  - Alternative chemical modifications reverse the binding orientation of a
      pharmacophore scaffold in the active site of macrophage migration inhibitory
      factor.
AB  - Pharmacophores are chemical scaffolds upon which changes in chemical moieties (R
      groups) at specific sites are made to identify a combination of R-groups that
      increases the therapeutic potency of a small molecule inhibitor while minimizing
      adverse effects. We developed a pharmacophore based on a carbonyloxime (OXIM)
      scaffold for macrophage migration inhibitory factor (MIF), a protein involved in
      the pathology of sepsis, to validate that inhibition of a catalytic site could
      produce therapeutic benefits. We studied the crystal structures of MIF.OXIM-based
      inhibitors and found two opposite orientations for binding to the active site
      that were dependent on the chemical structures of an R-group. One orientation was
      completely unexpected based on previous studies with hydroxyphenylpyruvate and
      (S,R)-3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazole acetic acid methyl ester (ISO
      1). We further confirmed that the unexpected binding mode targets MIF in cellular
      studies by showing that one compound, OXIM-11, abolished the counter-regulatory
      activity of MIF on anti-inflammatory glucocorticoid action. OXIM-11 treatment of
      mice, initiated 24 h after the onset of cecal ligation and puncture-induced
      sepsis, significantly improved survival when compared with vehicle-treated
      controls, confirming that inhibition of the MIF catalytic site could produce
      therapeutic effects. The crystal structures of the MIF inhibitor complexes
      provide insight for further structure-based drug design efforts.

PMID- 17526495
TI  - Fyn-mediated phosphorylation of NR2B Tyr-1336 controls calpain-mediated NR2B
      cleavage in neurons and heterologous systems.
AB  - Cleavage of the intracellular carboxyl terminus of the N-methyl-d-aspartate
      (NMDA) receptor 2 subunit (NR2) by calpain regulates NMDA receptor function and
      localization. Here, we show that Fyn-mediated phosphorylation of NR2B controls
      calpain-mediated NR2B cleavage. In cultured neurons, calpain-mediated NR2B
      cleavage is significantly attenuated by blocking NR2B phosphorylation of Tyr
      1336, but not Tyr-1472, via inhibition of Src family kinase activity or
      decreasing Fyn levels by small interfering RNA. In HEK cells, mutation of Tyr
      1336 eliminates the potentiating effect of Fyn on calpain-mediated NR2B cleavage.
      The potentiation of NR2B cleavage by Fyn is limited to cell surface receptors and
      is associated with calpain translocation to plasma membranes during NMDA receptor
      activation. Finally, reducing full-length NR2B by calpain does not decrease
      extrasynaptic NMDA receptor function, and truncated NR1/2B receptors similar to
      those generated by calpain have electrophysiological properties matching those of
      wild-type receptors. Thus, the Fyn-controlled regulation of NMDA receptor
      cleavage by calpain may play critical roles in controlling NMDA receptor
      properties during synaptic plasticity and excitotoxicity.

PMID- 17526496
TI  - Fibrillogenic nuclei composed of P301L mutant tau induce elongation of P301L tau
      but not wild-type tau.
AB  - Frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17), an
      autosomal, dominantly inherited neurodegenerative disorder caused by tau gene
      mutations, is neuropathologically characterized by intraneuronal filamentous
      inclusions of hyperphosphorylated tau protein. Biochemical and immunocytochemical
      analyses have shown that only mutant tau is deposited in patients harboring P301L
      missense mutation, whereas both wild-type and mutant tau are deposited in
      patients harboring R406W mutation (Miyasaka, T., Morishima-Kawashima, M., Ravid,
      R., Kamphorst, W., Nagashima, K., and Ihara, Y. (2001) J. Neuropathol. Exp.
      Neurol. 60, 872- 884 and Miyasaka, T., Morishima-Kawashima, M., Ravid, R.,
      Heutink, P., van Swieten, J. C., Nagashima, K., and Ihara, Y. (2001) Am. J.
      Pathol. 158, 373-379). Here we have tested the nucleation ability of monomeric
      tau and the seeding ability of fibrillogenic nuclei obtained from bacterially
      expressed human tau. P301L mutant tau showed a higher nucleation ability than
      wild-type tau, whereas R406W mutant tau shows similar ability to wild-type tau.
      Surprisingly, fibrillogenic nuclei composed of P301L mutant tau enhanced the
      assembly of P301L mutant tau into filaments but did not promote filament
      formation from wild-type tau. In contrast, nuclei composed of R406W mutant tau
      supported filament formation from both wild-type tau and R406W mutant tau, as did
      nuclei composed of wild-type tau. Proteolytic analyses indicated that the
      substructure of nuclei composed of P301L mutant tau was different from that of
      nuclei composed of wild-type or R406W mutant tau. Thus, the interaction between
      fibrillogenic nuclei and monomeric protein appears to play an important role in
      the mechanism of tau filament assembly.

PMID- 17526497
TI  - The Metarhizium anisopliae Perilipin Homolog MPL1 Regulates Lipid Metabolism,
      Appressorial Turgor Pressure, and Virulence.
AB  - Cells store lipids in droplets. Studies addressing how mammals control lipid
      based energy homeostasis have implicated proteins of the PAT domain family, such
      as perilipin that surrounds the lipid droplets. Perilipin knock-out mice are lean
      and resistant to obesity. Factors that mediate lipid storage in fungi are still
      unknown. Here we describe a gene (Mpl1) in the economically important insect
      fungal pathogen Metarhizium anisopliae that has structural similarities to
      mammalian perilipins. Consistent with a role in lipid storage, Mpl1 is
      predominantly expressed when M. anisopliae is engaged in accumulating lipids and
      ectopically expressed green fluorescent protein-tagged MPL1 (Metarhizium
      perilipin-like protein) localized to lipid droplets. Mutant M. anisopliae lacking
      MPL1 have thinner hyphae, fewer lipid droplets, particularly in appressoria
      (specialized infection structures at the end of germ tubes), and a decrease in
      total lipids. Mpl1 therefore acts in a perilipin-like manner suggesting an
      evolutionary conserved function in lipid metabolism. However, reflecting general
      differences between animal and fungal lineages, these proteins have also been
      selected to cope with different tasks. Thus, turgor generation by DeltaMpl1
      appressoria is dramatically reduced indicating that lipid droplets are required
      for solute accumulation. This was linked with the reduced ability to breach
      insect cuticle so that Mpl1 is a pathogenicity determinant. Blast searches of
      fungal genomes revealed that perilipin homologs are found only in pezizomycotinal
      ascomycetes and occur as single copy genes. Expression of Mpl1 in yeast cells, a
      fungus that lacks a perilipin-like gene, blocked their ability to mobilize lipids
      during starvation conditions.

PMID- 17526498
TI  - Multisubunit RNA polymerases melt only a single DNA base pair downstream of the
      active site.
AB  - To extend the nascent transcript, RNA polymerases must melt the DNA duplex
      downstream from the active site to expose the next acceptor base for substrate
      binding and incorporation. A number of mechanisms have been proposed to account
      for the manner in which the correct substrate is selected, and these differ in
      their predictions as to how far the downstream DNA is melted. Using fluorescence
      quenching experiments, we provide evidence that cellular RNA polymerases from
      bacteria and yeast melt only one DNA base pair downstream from the active site.
      These data argue against a model in which multiple NTPs are lined up downstream
      of the active site.

PMID- 17526499
TI  - The structure of apolipoprotein A-I in high density lipoproteins.

PMID- 17526500
TI  - Bax inhibitor-1 regulates endoplasmic reticulum stress-associated reactive oxygen
      species and heme oxygenase-1 expression.
AB  - The Bax inhibitor-1 (BI-1) is an anti-apoptotic protein that is located in
      endoplasmic reticulum (ER) membranes and protects cells from ER stress-induced
      apoptosis. The ER is associated with generation of reactive oxygen species (ROS)
      through oxidative protein folding. This study examined the role of BI-1 in the
      regulation of ER stress-induced accumulation of ROS and expression of unfolded
      protein response-associated proteins. BI-1 reduced the expression levels of
      glucose response protein 78, C/EBP homologous protein, phospho-eukaryotic
      initiation factor 2alpha, IRE1alpha, XBP-1, and phospho-JNK and inhibited the
      cleavage of ATF-6alpha p-90, leading to the inhibition of ROS. Although ROS
      scavengers offer some protection against ER stress-induced apoptosis, the
      expression of pro-apoptotic ER stress proteins was not affected. This study shows
      that the response of unfolded proteins is followed by ROS accumulation under ER
      stress, which is regulated in BI-1 cells. The mechanism for these BI-1-associated
      functions involves the expression of heme oxygenase-1 (HO-1) through nuclear
      factor erythroid 2-related factor 2. In BI-1 cells, the transfection of HO-1
      small interfering RNA completely abolished the BI-1-induced protection. The
      endogenous expression of HO-1 through ER stress-initiated ROS is believed to be
      as a protection signal. In conclusion, these observations suggest that BI-1 can
      inhibit the ER stress proteins as well as the accumulation of ROS, thereby
      protecting the cells. Moreover, HO-1 plays an important role in the BI-1
      associated protection against ER stress.

PMID- 17526501
TI  - Substrate specificity of the OqxAB multidrug resistance pump in Escherichia coli
      and selected enteric bacteria.
AB  - OBJECTIVES: A plasmid-encoded multidrug efflux pump, OqxAB, identified in
      Escherichia coli of porcine origin, was tested for substrate specificity against
      selected antibiotics, detergents and disinfectants. The ability of horizontal
      transfer to food-borne pathogens of the Enterobacteriaceae family was also
      investigated. METHODS: The MICs of selected substrates were determined with a
      broth dilution assay using two isogenic E. coli strains, except for the presence
      of the oqxAB operon. A derivative of the plasmid encoding OqxAB (pOLA52) was
      constructed and horizontal transfer to Salmonella Typhimurium, Klebsiella
      pneumoniae, Kluyvera sp. and Enterobacter aerogenes was investigated. The effect
      of the presence of the OqxAB pump on susceptibility for selected compounds was
      investigated using broth dilution assays. RESULTS: The OqxAB pump conferred
      antimicrobial resistance or reduced susceptibility towards a variety of
      substrates in E. coli. These included animal growth promoters, antimicrobials,
      disinfectants and detergents. pOLA52 could readily be transferred to
      enterobacterial pathogens. Transconjugants showed reduced susceptibility towards
      chloramphenicol, ciprofloxacin and olaquindox. CONCLUSIONS: The plasmid-encoded
      OqxAB pump has a wide substrate specificity and can be transferred between
      Enterobacteriaceae conferring reduced susceptibility to a multitude of
      substrates. These results could indicate some dependence on the outer membrane
      proteins present in the different species.

PMID- 17526503
TI  - Rapid and widespread dissemination of multidrug-resistant blaCMY-2 Salmonella
      Typhimurium in Mexico.
AB  - OBJECTIVES: We describe the emergence and dissemination of multidrug-resistant
      (MDR) Salmonella Typhimurium in humans, retail meat and food animals from
      Yucatan, Mexico. METHODS: Salmonella Typhimurium isolates were collected through
      an active surveillance system and tested for susceptibility to 12 antimicrobial
      agents. Isolates that were non-susceptible to ceftriaxone were tested with 10
      additional antimicrobials and assayed by PCR for the presence of CMY, CTX-M, SHV,
      TEM and OXA beta-lactamase genes. Plasmid-borne phenotypes were identified by
      transfer to susceptible Escherichia coli. Isolates from humans, retail meat and
      food animals were compared by PFGE to determine genetic relatedness. RESULTS: MDR
      Salmonella Typhimurium containing a plasmid-mediated blaCMY-2 AmpC beta-lactamase
      rose from 0% (0/27) during 2000 and 2001 to 75% (63/84) in 2004 and 2005
      (P<0.0001). MDR blaCMY-2 Salmonella Typhimurium (n=115) was most common in ill
      children (44.3%) and pork or swine intestine (36.5%). In several cities, MDR
      blaCMY-2 Salmonella Typhimurium from retail meat or swine intestine exhibited
      PFGE patterns and antibiograms indistinguishable from those in strains recovered
      from hospitalized children. The CMY gene was transferred to E. coli by
      electroporation, along with resistance to three to six other antimicrobials.
      Children with MDR blaCMY-2 Salmonella Typhimurium infection (n=39) had a higher
      frequency of systemic infection (13% versus 0%), mortality (8% versus 0%) and
      hospital re-admission due to protracted diarrhoea (28% versus 17%) than children
      with non-MDR-Salmonella Typhimurium (n=24), although the difference was not
      statistically significant. CONCLUSIONS: The rapid and widespread dissemination of
      MDR blaCMY-2 Salmonella Typhimurium in Mexico calls for urgent interventions to
      contain this potentially fatal pathogen.

PMID- 17526504
TI  - Is the chest pain in cardiac syndrome X due to subendocardial ischaemia?

PMID- 17526505
TI  - STEMI and NSTEMI: the dangerous brothers.

PMID- 17526506
TI  - It's the metabolism, stupid! Why electrophysiologists should be interested in
      biomarkers of heart failure.

PMID- 17526507
TI  - The evaluation of genetic tests.
AB  - Scientific advances in genetics and molecular biology have been very successful
      in advancing our knowledge of biological mechanisms in health and disease, and in
      catalysing a variety of technological innovations. The number of genetic tests
      available has consequently increased exponentially over the last few years. Their
      development has not been accompanied by processes and systems to evaluate these
      tests in a proper and formal manner to establish their clinical validity and
      utility. A framework for the evaluation of genetic tests has been developed. This
      paper reviews the current practice of genetic test evaluation, highlighting the
      limitations and future challenges in this area of public health.

PMID- 17526508
TI  - Tachycardia after pacemaker implantation in a patient with complete
      atrioventricular block.
AB  - The atrioventricular (AV) node allows ante- and retrograde conduction between
      atria and ventricles. It is commonly assumed that these AV nodal conduction
      properties go hand in hand. However, ante- and retrograde AV conduction can be
      completely independent from each other in individual patients. We report about a
      patient with permanent AV block III degrees requiring implantation of a
      pacemaker. As soon as a dual-chamber device was connected to the implanted leads,
      a tachycardia started at the maximum tracking rate, which was subsequently
      reprogrammed from 120 to 170 bpm. Non-invasive electrophysiologic testing showed
      that this patient demonstrated 1:1 ventriculoatrial (VA) conduction up to 170 bpm
      leading to endless loop tachycardia (ELT) while the antegrade AV block III
      degrees persisted. This case impressively illustrates that one has to take into
      account that patients with antegrade AV block III degrees may still have a high
      VA conduction capacity leading to ELT. Dual-chamber devices therefore have to be
      programmed accordingly, activating dedicated reactions after ventricular
      premature beats and automatic ELT detection and termination algorithms.

PMID- 17526509
TI  - Serum BNP, hs-C-reactive protein, procollagen to assess the risk of ventricular
      tachycardia in ICD recipients after myocardial infarction.
AB  - AIMS: Ventricular arrhythmia is the main cause of sudden cardiac death.
      Intracardiac strain, myocardial and extracellular matrix remodelling, and
      subsequent myocardial fibrosis are involved in arrhythmia pathogenesis. The
      present study investigates the relationship between cardiac fibrosis [procollagen
      type I aminoterminal peptide (PINP), procollagen type III aminoterminal peptide
      (PIIINP), TIMP1, membrane metalloproteinase I], pressure overload [brain
      natriuretic peptide (BNP)] inflammation [high sensitivity (hs)-C-reactive
      protein] serum markers, and the incidence of ventricular tachycardia (VT) in
      implantable cardioverter-defibrillators (ICD) recipients. METHODS AND RESULTS:
      Serum markers were collected in 121 patients implanted for spontaneous sustained
      VT and a prior history of myocardial infarction. VT incidence was obtained during
      ICD interrogation. Over a 1 year period, 38 patients (31%) experienced at least 1
      VT. In a multivariate analysis, a left ventricular ejection fraction <0.35 (OR =
      2.19, 95%CI 1.00-4.79, P = 0.049), an increased serum BNP (OR = 3.75, 95%CI 1.46
      9.67, P = 0.014), an increased hs-C-reactive protein (OR = 3.2, 95%CI 1.26-8.10,
      P = 0.006), an increased PINP (OR = 3.71, 95%CI 1.40-9.88, P = 0.009), and a
      decreased PIIINP (OR = 0.21, 95%CI 0.08-0.59, P = 0.003) were associated with a
      higher VT incidence. CONCLUSION: In coronary artery disease patients: (1) BNP is
      not only a marker of left ventricular dysfunction, but also a marker of VT; (2)
      combined 'high PINP and low PIIINP' is a strong VT marker; and 3) inflammatory
      process is involved in VT pathogenesis.

PMID- 17526510
TI  - Children with human immunodeficiency virus infection admitted to a paediatric
      intensive care unit in South Africa.
AB  - BACKGROUND: Early data regarding the outcome of human immunodeficiency virus
      (HIV)-infected children in paediatric intensive care units (PICU) suggested
      mortality as high as 100%. Recent studies report mortality of 38%. Survival
      depends on the indication for admission. OBJECTIVES: To describe the prevalence,
      duration of stay, and outcome of HIV-infected patients in a single PICU over a 1
      year period. Additional objectives included describing the indications for
      admission as well as the clinical and laboratory characteristics of HIV-infected
      infants and children requiring PICU admission. METHOD: Retrospective chart review
      of all children with serological proof of HIV admitted to PICU at Tygerberg
      Children's Hospital from 1 January to 31 December 2003. RESULTS: Of the 465
      patients admitted, 47 (10%) were HIV-infected. For HIV-infected children the
      median age on admission was 4 months. The median duration of stay was 6 days,
      significantly longer than for the non-HIV group (p = 0.0001). Fifty-seven percent
      had advanced clinical and immunological disease. Seventeen died in PICU and four
      shortly afterwards, poor PICU outcome was significantly associated with HIV
      status (p = 0.001). Lower total lymphocyte count (p = 0.004) and higher gamma
      globulin level (p = 0.04) were paradoxically the only findings significantly
      associated with survival. Acute respiratory failure (ARF) accounted for 76% of
      admissions, including Pneumocystis jiroveci in 38%. Fifty-one percent had
      evidence of cytomegalovirus infection. CONCLUSIONS: HIV-infected children
      requiring PICU can survive despite the lack of availability of antiretroviral
      therapy.

PMID- 17526511
TI  - Drug resistance in tuberculosis.

PMID- 17526512
TI  - ESTpass: a web-based server for processing and annotating expressed sequence tag
      (EST) sequences.
AB  - We present a web-based server, called ESTpass, for processing and annotating
      sequence data from expressed sequence tag (EST) projects. ESTpass accepts a FASTA
      formatted EST file and its quality file as inputs, and it then executes a back
      end EST analysis pipeline consisting of three consecutive steps. The first is
      cleansing the input EST sequences. The second is clustering and assembling the
      cleansed EST sequences using d2_cluster and CAP3 programs and producing putative
      transcripts. From the CAP3 output, ESTpass detects chimeric EST sequences which
      are confirmed through comparison with the nr database. The last step is
      annotating the putative transcript sequences using RefSeq, InterPro, GO and KEGG
      gene databases according to user-specified options. The major advantages of
      ESTpass are the integration of cleansing and annotating processes, rigorous
      chimeric EST detection, exhaustive annotation, and email reporting to inform the
      user about the progress and to send the analysis results. The ESTpass results
      include three reports (summary, cleansing and annotation) and download function,
      as well as graphic statistics. They can be retrieved and downloaded using a
      standard web browser. The server is available at http://estpass.kobic.re.kr/.

PMID- 17526513
TI  - Article withdrawn: GNARE: a grid-based server for the analysis of user submitted
      genomes.

PMID- 17526514
TI  - ProtSweep, 2Dsweep and DomainSweep: protein analysis suite at DKFZ.
AB  - The wealth of transcript information that has been made publicly available in
      recent years has led to large pools of individual web sites offering access to
      bioinformatics software. However, finding out which services exist, what they can
      or cannot do, how to use them and how to feed results from one service to the
      next one in the right format can be very time and resource consuming, especially
      for non-experts. Automating this task, we present a suite of protein annotation
      pipelines (tasks) developed at the German Cancer Research Centre (DKFZ) oriented
      to protein annotation by homology (ProtSweep), by domain analysis (DomainSweep),
      and by secondary structure elements (2Dsweep). The aim of these tasks is to
      perform an exhaustive structural and functional analysis employing a wide variety
      of methods in combination with the most updated public databases. The three
      servers are available for academic users at the HUSAR open server
      http://genius.embnet.dkfz-heidelberg.de/menu/biounit/open-husar/

PMID- 17526515
TI  - Zinc Finger Targeter (ZiFiT): an engineered zinc finger/target site design tool.
AB  - Zinc Finger Targeter (ZiFiT) is a simple and intuitive web-based tool that
      facilitates the design of zinc finger proteins (ZFPs) that can bind to specific
      DNA sequences. The current version of ZiFiT is based on a widely employed method
      of ZFP design, the 'modular assembly' approach, in which pre-existing individual
      zinc fingers are linked together to recognize desired target DNA sequences.
      Several research groups have described experimentally characterized zinc finger
      modules that bind many of the 64 possible DNA triplets. ZiFiT leverages the
      combined capabilities of three of the largest and best characterized module
      archives by enabling users to select fingers from any of these sets. ZiFiT
      searches a query DNA sequence for target sites for which a ZFP can be designed
      using modules available in one or more of the three archives. In addition, ZiFiT
      output facilitates identification of specific zinc finger modules that are
      publicly available from the Zinc Finger Consortium. ZiFiT is freely available at
      http://bindr.gdcb.iastate.edu/ZiFiT/.

PMID- 17526516
TI  - MADAP, a flexible clustering tool for the interpretation of one-dimensional
      genome annotation data.
AB  - A recurring task in the analysis of mass genome annotation data from high
      throughput technologies is the identification of peaks or clusters in a noisy
      signal profile. Examples of such applications are the definition of promoters on
      the basis of transcription start site profiles, the mapping of transcription
      factor binding sites based on ChIP-chip data and the identification of
      quantitative trait loci (QTL) from whole genome SNP profiles. Input to such an
      analysis is a set of genome coordinates associated with counts or intensities.
      The output consists of a discrete number of peaks with respective volumes,
      extensions and center positions. We have developed for this purpose a flexible
      one-dimensional clustering tool, called MADAP, which we make available as a web
      server and as standalone program. A set of parameters enables the user to
      customize the procedure to a specific problem. The web server, which returns
      results in textual and graphical form, is useful for small to medium-scale
      applications, as well as for evaluation and parameter tuning in view of large
      scale applications, requiring a local installation. The program written in C++
      can be freely downloaded from ftp://ftp.epd.unil.ch/pub/software/unix/madap. The
      MADAP web server can be accessed at http://www.isrec.isb-sib.ch/madap/.

PMID- 17526517
TI  - Phosphorylation in the serine/threonine 2609-2647 cluster promotes but is not
      essential for DNA-dependent protein kinase-mediated nonhomologous end joining in
      human whole-cell extracts.
AB  - Previous work suggested that phosphorylation of DNA-PKcs at several
      serine/threonine (S/T) residues at positions 2609-2647 promotes DNA-PK-dependent
      end joining. In an attempt to clarify the role of such phosphorylation, end
      joining was examined in extracts of DNA-PKcs-deficient M059J cells. Joining of
      ends requiring gap filling prior to ligation was completely dependent on
      complementation of these extracts with exogenous DNA-PKcs. DNA-PKcs with either
      S/T --> A or S/T --> D substitutions at all six sites in the 2609-2647 cluster
      also supported end joining, but with markedly lower efficiency than wild-type
      protein. The residual end joining was greater with the S/T --> D-substituted than
      with the S/T --> A-substituted protein. A specific inhibitor of the kinase
      activity of DNA-PK, KU57788, completely blocked end joining promoted by wild type
      as well as both mutant forms of DNA-PK, while inhibition of ATM kinase did not.
      The fidelity of end joining was not affected by the mutant DNA-PKcs alleles or
      the inhibitors. Overall, the results support a role for autophosphorylation of
      the 2609-2647 cluster in promoting end joining and controlling the accessibility
      of DNA ends, but suggest that DNA-PK-mediated phosphorylation at other sites, on
      either DNA-PKcs or other proteins, is at least as important as the 2609-2647
      cluster in regulating end joining.

PMID- 17526518
TI  - Cell cycle regulation as a mechanism for functional separation of the apparently
      redundant uracil DNA glycosylases TDG and UNG2.
AB  - Human Thymine-DNA Glycosylase (TDG) is a member of the uracil DNA glycosylase
      (UDG) superfamily. It excises uracil, thymine and a number of chemical base
      lesions when mispaired with guanine in double-stranded DNA. These activities are
      not unique to TDG; at least three additional proteins with similar enzymatic
      properties are present in mammalian cells. The successful co-evolution of these
      enzymes implies the existence of non-redundant biological functions that must be
      coordinated. Here, we report cell cycle regulation as a mechanism for the
      functional separation of apparently redundant DNA glycosylases. We show that
      cells entering S-phase eliminate TDG through the ubiquitin-proteasome system and
      then maintain a TDG-free condition until G2. Incomplete degradation of
      ectopically expressed TDG impedes S-phase progression and cell proliferation. The
      mode of cell cycle regulation of TDG is strictly inverse to that of UNG2, which
      peaks in and throughout S-phase and then declines to undetectable levels until it
      appears again just before the next S-phase. Thus, TDG- and UNG2-dependent base
      excision repair alternates throughout the cell cycle, and the ubiquitin
      proteasome pathway constitutes the underlying regulatory system.

PMID- 17526519
TI  - The M-Coffee web server: a meta-method for computing multiple sequence alignments
      by combining alternative alignment methods.
AB  - The M-Coffee server is a web server that makes it possible to compute multiple
      sequence alignments (MSAs) by running several MSA methods and combining their
      output into one single model. This allows the user to simultaneously run all his
      methods of choice without having to arbitrarily choose one of them. The MSA is
      delivered along with a local estimation of its consistency with the individual
      MSAs it was derived from. The computation of the consensus multiple alignment is
      carried out using a special mode of the T-Coffee package [Notredame, Higgins and
      Heringa (T-Coffee: a novel method for fast and accurate multiple sequence
      alignment. J. Mol. Biol. 2000; 302: 205-217); Wallace, O'Sullivan, Higgins and
      Notredame (M-Coffee: combining multiple sequence alignment methods with T-Coffee.
      Nucleic Acids Res. 2006; 34: 1692-1699)] Given a set of sequences (DNA or
      proteins) in FASTA format, M-Coffee delivers a multiple alignment in the most
      common formats. M-Coffee is a freeware open source package distributed under a
      GPL license and it is available either as a standalone package or as a web
      service from www.tcoffee.org.

PMID- 17526520
TI  - Single-molecule analysis of 1D diffusion and transcription elongation of T7 RNA
      polymerase along individual stretched DNA molecules.
AB  - Using total internal reflection fluorescence microscopy, we directly visualize in
      real-time, the 1D Brownian motion and transcription elongation of T7 RNA
      polymerase along aligned DNA molecules bound to substrates by molecular combing.
      We fluorescently label T7 RNA polymerase with antibodies and use flow to convect
      them orthogonally to the DNA alignment direction, permitting observation and
      estimation of the protein diffusivity along the DNA at the single-molecule level.
      Our observations suggest that the 1D diffusion coefficient varies from molecule
      to molecule over the range 6.1 x 10(-11) cm2/s to 4.3 x 10(-9) cm2/s. We also
      observe binding and transcription by T7 RNA polymerases on single combed T7 DNA
      molecules with an apparent association rate of 1.6 microM(-1)s(-1). From the
      measured dependence of the rate of transcription on concentration of nucleotide
      triphosphate, we infer that the combed DNA molecules capable of interacting with
      proteins are under an average tension of 25 pN.

PMID- 17526521
TI  - GeneTrail--advanced gene set enrichment analysis.
AB  - We present a comprehensive and efficient gene set analysis tool, called
      'GeneTrail' that offers a rich functionality and is easy to use. Our web-based
      application facilitates the statistical evaluation of high-throughput genomic or
      proteomic data sets with respect to enrichment of functional categories.
      GeneTrail covers a wide variety of biological categories and pathways, among
      others KEGG, TRANSPATH, TRANSFAC, and GO. Our web server provides two common
      statistical approaches, 'Over-Representation Analysis' (ORA) comparing a
      reference set of genes to a test set, and 'Gene Set Enrichment Analysis' (GSEA)
      scoring sorted lists of genes. Besides other newly developed features,
      GeneTrail's statistics module includes a novel dynamic-programming algorithm that
      improves the P-value computation of GSEA methods considerably. GeneTrail is
      freely accessible at http://genetrail.bioinf.uni-sb.de.

PMID- 17526522
TI  - KAAS: an automatic genome annotation and pathway reconstruction server.
AB  - The number of complete and draft genomes is rapidly growing in recent years, and
      it has become increasingly important to automate the identification of functional
      properties and biological roles of genes in these genomes. In the KEGG database,
      genes in complete genomes are annotated with the KEGG orthology (KO) identifiers,
      or the K numbers, based on the best hit information using Smith-Waterman scores
      as well as by the manual curation. Each K number represents an ortholog group of
      genes, and it is directly linked to an object in the KEGG pathway map or the
      BRITE functional hierarchy. Here, we have developed a web-based server called
      KAAS (KEGG Automatic Annotation Server: http://www.genome.jp/kegg/kaas/) i.e. an
      implementation of a rapid method to automatically assign K numbers to genes in
      the genome, enabling reconstruction of KEGG pathways and BRITE hierarchies. The
      method is based on sequence similarities, bi-directional best hit information and
      some heuristics, and has achieved a high degree of accuracy when compared with
      the manually curated KEGG GENES database.

PMID- 17526523
TI  - A server and database for dipole moments of proteins.
AB  - An Internet server at http://bip.weizmann.ac.il/dipol calculates the net charge,
      dipole moment and mean radius of any 3D protein structure or its constituent
      peptide chains, and displays the dipole vector superimposed on a ribbon backbone
      of the protein. The server can also display the angle between the dipole and a
      selected list of amino acid residues in the protein. When the net charges and
      dipole moments of approximately 12 000 non-homologous PDB biological units
      (PISCES set), and their unique chains of length 50 residues or longer, were
      examined, the great majority of both charges and dipoles fell into a very narrow
      range of values, with long extended tails containing a few extreme outliers. In
      general, there is no obvious relation between a protein's charge or dipole moment
      and its structure or function, so that its electrostatic properties are highly
      specific to the particular protein, except that the majority of chains with very
      large positive charges or dipoles bind to ribosomes or interact with nucleic
      acids.

PMID- 17526524
TI  - pKNOT: the protein KNOT web server.
AB  - Knotted proteins are more commonly observed in recent years due to the enormously
      growing number of structures in the Protein Data Bank (PDB). Studies show that
      the knot regions contribute to both ligand binding and enzyme activity in
      proteins such as the chromophore-binding domain of phytochrome, ketol-acid
      reductoisomerase or SpoU methyltransferase. However, there are still many
      misidentified knots published in the literature due to the absence of a
      convenient web tool available to the general biologists. Here, we present the
      first web server to detect the knots in proteins as well as provide information
      on knotted proteins in PDB-the protein KNOT (pKNOT) web server. In pKNOT, users
      can either input PDB ID or upload protein coordinates in the PDB format. The
      pKNOT web server will detect the knots in the protein using the Taylor's
      smoothing algorithm. All the detected knots can be visually inspected using a
      Java-based 3D graphics viewer. We believe that the pKNOT web server will be
      useful to both biologists in general and structural biologists in particular.

PMID- 17526525
TI  - The electrostatic characteristics of G.U wobble base pairs.
AB  - G.U wobble base pairs are the most common and highly conserved non-Watson-Crick
      base pairs in RNA. Previous surface maps imply uniformly negative electrostatic
      potential at the major groove of G.U wobble base pairs embedded in RNA helices,
      suitable for entrapment of cationic ligands. In this work, we have used a Poisson
      Boltzmann approach to gain a more detailed and accurate characterization of the
      electrostatic profile. We found that the major groove edge of an isolated G.U
      wobble displays distinctly enhanced negativity compared with standard GC or AU
      base pairs; however, in the context of different helical motifs, the
      electrostatic pattern varies. G.U wobbles with distinct widening have similar
      major groove electrostatic potentials to their canonical counterparts, whereas
      those with minimal widening exhibit significantly enhanced electronegativity,
      ranging from 0.8 to 2.5 kT/e, depending upon structural features. We propose that
      the negativity at the major groove of G.U wobble base pairs is determined by the
      combined effect of the base atoms and the sugar-phosphate backbone, which is
      impacted by stacking pattern and groove width as a result of base sequence. These
      findings are significant in that they provide predictive power with respect to
      which G.U sites in RNA are most likely to bind cationic ligands.

PMID- 17526526
TI  - General transfer matrix formalism to calculate DNA-protein-drug binding in gene
      regulation: application to OR operator of phage lambda.
AB  - The transfer matrix methodology is proposed as a systematic tool for the
      statistical-mechanical description of DNA-protein-drug binding involved in gene
      regulation. We show that a genetic system of several cis-regulatory modules is
      calculable using this method, considering explicitly the site-overlapping,
      competitive, cooperative binding of regulatory proteins, their multilayer
      assembly and DNA looping. In the methodological section, the matrix models are
      solved for the basic types of short- and long-range interactions between DNA
      bound proteins, drugs and nucleosomes. We apply the matrix method to gene
      regulation at the O(R) operator of phage lambda. The transfer matrix formalism
      allowed the description of the lambda-switch at a single-nucleotide resolution,
      taking into account the effects of a range of inter-protein distances. Our
      calculations confirm previously established roles of the contact CI-Cro-RNAP
      interactions. Concerning long-range interactions, we show that while the DNA loop
      between the O(R) and O(L) operators is important at the lysogenic CI
      concentrations, the interference between the adjacent promoters P(R) and P(RM)
      becomes more important at small CI concentrations. A large change in the
      expression pattern may arise in this regime due to anticooperative interactions
      between DNA-bound RNA polymerases. The applicability of the matrix method to more
      complex systems is discussed.

PMID- 17526527
TI  - RNAbor: a web server for RNA structural neighbors.
AB  - RNAbor provides a new tool for researchers in the biological and related sciences
      to explore important aspects of RNA secondary structure and folding pathways.
      RNAbor computes statistics concerning delta-neighbors of a given input RNA
      sequence and structure (the structure can, for example, be the minimum free
      energy (MFE) structure). A delta-neighbor is a structure that differs from the
      input structure by exactly delta base pairs, that is, it can be obtained from the
      input structure by adding and/or removing exactly delta base pairs. For each
      distance delta RNAbor computes the density of delta-neighbors, the number of
      delta-neighbors, and the MFE structure, or MFE (delta) structure, among all delta
      neighbors. RNAbor can be used to study possible folding pathways, to determine
      alternate low-energy structures, to predict potential nucleation sites and to
      explore structural neighbors of an intermediate, biologically active structure.
      The web server is available at http://bioinformatics.bc.edu/clotelab/RNAbor.

PMID- 17526528
TI  - CytoSVM: an advanced server for identification of cytokine-receptor interactions.
AB  - The interactions between cytokines and their complementary receptors are the
      gateways to properly understand a large variety of cytokine-specific cellular
      activities such as immunological responses and cell differentiation. To discover
      novel cytokine-receptor interactions, an advanced support vector machines (SVMs)
      model, CytoSVM, was constructed in this study. This model was iteratively trained
      using 449 mammal (except rat) cytokine-receptor interactions and about 1 million
      virtually generated positive and negative vectors in an enriched way. Final
      independent evaluation by rat's data received sensitivity of 97.4%, specificity
      of 99.2% and the Matthews correlation coefficient (MCC) of 0.89. This performance
      is better than normal SVM-based models. Upon this well-optimized model, a web
      based server was created to accept primary protein sequence and present its
      probabilities to interact with one or several cytokines. Moreover, this model was
      applied to identify putative cytokine-receptor pairs in the whole genomes of
      human and mouse. Excluding currently known cytokine-receptor interactions, total
      1609 novel cytokine-receptor pairs were discovered from human genome with
      probability approximately 80% after further transmembrane analysis. These cover
      220 novel receptors (excluding their isoforms) for 126 human cytokines. The
      screening results have been deposited in a database. Both the server and the
      database can be freely accessed at
      http://bioinf.xmu.edu.cn/software/cytosvm/cytosvm.php.

PMID- 17526529
TI  - SNAP: predict effect of non-synonymous polymorphisms on function.
AB  - Many genetic variations are single nucleotide polymorphisms (SNPs). Non
      synonymous SNPs are 'neutral' if the resulting point-mutated protein is not
      functionally discernible from the wild type and 'non-neutral' otherwise. The
      ability to identify non-neutral substitutions could significantly aid targeting
      disease causing detrimental mutations, as well as SNPs that increase the fitness
      of particular phenotypes. Here, we introduced comprehensive data sets to assess
      the performance of methods that predict SNP effects. Along we introduced SNAP
      (screening for non-acceptable polymorphisms), a neural network-based method for
      the prediction of the functional effects of non-synonymous SNPs. SNAP needs only
      sequence information as input, but benefits from functional and structural
      annotations, if available. In a cross-validation test on over 80,000 mutants,
      SNAP identified 80% of the non-neutral substitutions at 77% accuracy and 76% of
      the neutral substitutions at 80% accuracy. This constituted an important
      improvement over other methods; the improvement rose to over ten percentage
      points for mutants for which existing methods disagreed. Possibly even more
      importantly SNAP introduced a well-calibrated measure for the reliability of each
      prediction. This measure will allow users to focus on the most accurate
      predictions and/or the most severe effects. Available at
      http://www.rostlab.org/services/SNAP.

PMID- 17526530
TI  - PI2PE: protein interface/interior prediction engine.
AB  - The side chains of the 20 types of amino acids, owing to a large extent to their
      different physical properties, have characteristic distributions in
      interior/surface regions of individual proteins and in interface/non-interface
      portions of protein surfaces that bind proteins or nucleic acids. These
      distributions have important structural and functional implications. We have
      developed accurate methods for predicting the solvent accessibility of amino
      acids from a protein sequence and for predicting interface residues from the
      structure of a protein-binding or DNA-binding protein. The methods are called
      WESA, cons-PPISP and DISPLAR, respectively. The web servers of these methods are
      now available at http://pipe.scs.fsu.edu. To illustrate the utility of these web
      servers, cons-PPISP and DISPLAR predictions are used to construct a structural
      model for a multicomponent protein-DNA complex.

PMID- 17526531
TI  - C-terminal regions of topoisomerase IIalpha and IIbeta determine isoform-specific
      functioning of the enzymes in vivo.
AB  - Topoisomerase II removes supercoils and catenanes generated during DNA metabolic
      processes such as transcription and replication. Vertebrate cells express two
      genetically distinct isoforms (alpha and beta) with similar structures and
      biochemical activities but different biological roles. Topoisomerase IIalpha is
      essential for cell proliferation, whereas topoisomerase IIbeta is required only
      for aspects of nerve growth and brain development. To identify the structural
      features responsible for these differences, we exchanged the divergent C-terminal
      regions (CTRs) of the two human isoforms (alpha 1173-1531 and beta 1186-1621) and
      tested the resulting hybrids for complementation of a conditional topoisomerase
      IIalpha knockout in human cells. Proliferation was fully supported by all enzymes
      bearing the alpha CTR. The alpha CTR also promoted chromosome binding of both
      enzyme cores, and was by itself chromosome-bound, suggesting a role in enzyme
      targeting during mitosis. In contrast, enzymes bearing the beta CTR supported
      proliferation only rarely and when expressed at unusually high levels. A similar
      analysis of the divergent N-terminal regions (alpha 1-27 and beta 1-43) revealed
      no role in isoform-specific functions. Our results show that it is the CTRs of
      human topoisomerase II that determine their isoform-specific functions in
      proliferating cells. They also indicate persistence of some functional redundancy
      between the two isoforms.

PMID- 17526532
TI  - Vascular access in haemodialysis patients: a modifiable risk factor for
      bacteraemia and death.
AB  - BACKGROUND: Bacteraemia and the development of sepsis syndrome is second only to
      cardiovascular disease as the leading cause of death in patients on renal
      replacement therapy. AIM: To determine the contributions of laboratory and
      clinical variables to the risk of bacteraemia and death in haemodialysis
      patients. DESIGN: Retrospective analysis. METHODS: We analysed all patients
      receiving haemodialysis in our renal unit at the beginning of January 2004
      (n=263), recording clinical and laboratory variables for each patient at study
      entry. Bacteraemia and mortality were recorded for the subsequent 18-month
      period. Multivariate analysis using a Cox proportional hazards model was used to
      test for independent associations between variables and outcomes. RESULTS: During
      the study period, 45 patients (17.1%) developed bacteraemia and 65 (24.7%) died.
      Under multivariate analysis, use of dialysis catheters at study entry was a major
      factor in the development of bacteraemia and death with hazard ratios (HR) of 5.4
      (p<0.001) and 2.8 (p=0.012), respectively, for tunnelled central venous catheters
      vs. arteriovenous fistulas (AVFs) and 3.1 (p=0.01) and 3.4 (p=0.001),
      respectively, for non-tunnelled central venous catheters vs. AVFs. Elevated CRP
      at study entry was independently associated with bacteraemia (HR 1.5 per unit log
      CRP, p=0.006). Low serum albumin (HR 0.92, p=0.005) was independently associated
      with death. DISCUSSION: Use of synthetic vascular access catheters and heightened
      inflammatory state both have strong independent associations with subsequent
      bacteraemia and death. Bacteraemia surveillance strategies should be developed,
      with consideration of vascular access type and baseline inflammatory state as key
      components.

PMID- 17526533
TI  - Childhood mental ability in relation to cause-specific accidents in adulthood:
      the 1970 British Cohort Study.
AB  - BACKGROUND: Few data link childhood mental ability (IQ) with risk of accidents,
      and most published studies have methodological limitations. AIM: To examine the
      relationship between scores from a battery of mental ability tests taken in
      childhood, and self-reported accidents between the ages of 16 and 30 years.
      METHODS: In the British Cohort study, a sample of 8172 cohort members born in
      Great Britain in 1970 had complete data for IQ score assessed at 10 years of age
      and accident data self-reported at age 30 years. RESULTS: The relationship
      between childhood IQ score and later risk of accident was complex, differing
      according to sex and the type of accident under consideration. Women with higher
      childhood IQ were more likely than those with lower scores to report having had
      an accident(s) while at work, in a vehicle, engaging in sports, and in
      unspecified circumstances. Adjustment for markers of socioeconomic position
      weakened or eliminated some of these relations, but higher childhood IQ remained
      associated with increased risk of sporting and unspecified accidents. Men with
      higher childhood IQ scores were less likely than those with lower scores to
      report accidents at work, but more likely to report accidents at home, playing
      sports or in unspecified circumstances. After adjustment for socioeconomic
      circumstances, higher childhood IQ in men remained associated with an increased
      risk of accidents at home or in unspecified circumstances. DISCUSSION: The
      relationship between childhood mental ability and accidents in adulthood is
      complex. As in other studies, socioeconomic position has an inconsistent
      relationship with non-fatal accident type.

PMID- 17526534
TI  - Is implanto-prosthodontic treatment available for haemodialysis patients?

PMID- 17526535
TI  - The impact of FTY720 (fingolimod) on vasodilatory function and arterial
      elasticity in renal transplant patients.
AB  - BACKGROUND: FTY720 has recently demonstrated a similar efficacy in prevention of
      acute graft rejection compared with mycophenolate mofetil (MMF) in a large phase
      III trial of de novo renal transplant recipients. Creatinine clearance, however,
      was significantly lower in FTY720-treated patients. In the present study, we
      examined the impact of FTY720 on vascular function in a subgroup of patients of
      this trial. METHODS: Eighteen patients (12 FTY720, 6 MMF) agreed to be enrolled
      for an analysis of vascular function. Vascular measurements were performed 1.5
      years post-transplant and were repeated 3 months after conversion of the patients
      from FTY720 to MMF. Arterial stiffness was assessed as augmentation index
      (AI(75)); endothelium-dependent and -independent vasodilation were measured
      sonographically as flow-mediated dilation (FMD) and as vasodilation after
      application of glyceroltrinitrate (GTN). RESULTS: Conversion from 2.5 mg FTY720
      to MMF led to a significant improvement of FMD (5.40 +/- 1.84 vs 7.77 +/- 3.36%,
      P 0.02). AI(75) and GTN tended to be higher after conversion without reaching
      significance (83 +/- 20.43 vs 78.69 +/- 15.39%, P 0.06; 13.76 +/- 4.52 vs 17.39
      +/- 3.76%, P 0.07). In the MMF group, AI(75), FMD and GTN did not significantly
      change during the observation period. CONCLUSION: The present study constitutes
      the first analysis of the impact of FTY720 on vascular function in humans and
      reveals an improvement of arterial vasodilatory function after discontinuation of
      FTY720 in de novo renal transplant recipients on cyclosporine.

PMID- 17526536
TI  - Calcimimetic increases osteoprotegerin and decreases fetuin-A levels in dialysis
      patients.

PMID- 17526537
TI  - Molecular characterization of two patients with severe LCAT deficiency.

PMID- 17526538
TI  - Does size matter?

PMID- 17526539
TI  - Transplant professionals vary in the long-term medical risks they communicate to
      potential living kidney donors: an international survey.
AB  - BACKGROUND: Discussing long-term medical risks with potential living donors is a
      vital aspect of informed consent. We considered whether there are global practice
      variations in the information communicated to potential living kidney donors.
      METHODS: Transplant professionals participated in a survey to determine which
      long-term risks are communicated to potential living kidney donors. Self
      administered questionnaires were distributed in person and by electronic mail.
      RESULTS: We surveyed 203 practitioners from 119 cities in 35 different countries.
      Sixty-three percent of participants were nephrologists, and 27% were surgeons.
      Risks of hypertension, proteinuria or kidney failure requiring dialysis were
      frequently discussed (usually over 80% of practitioners discussed each medical
      condition). However, many practitioners do not believe these risks are increased
      after donation, with surgeons being less convinced of long-term sequelae compared
      with nephrologists (P < 0.01). About 30% of practitioners discuss long-term risks
      of premature cardiovascular disease or death with potential donors. CONCLUSIONS:
      Transplant professionals vary in the long-term risks they communicate to
      potential donors. Improving consensus will enhance decision-making, and emphasize
      best practices which maintain good, long-term donor health.

PMID- 17526540
TI  - Renal replacement therapy for acute kidney injury in pregnancy.

PMID- 17526541
TI  - Adult and paediatric patients with minimal change nephrotic syndrome show no
      major alterations in glomerular expression of sulphated heparan sulphate domains.
AB  - BACKGROUND: Minimal change nephrotic syndrome (MCNS) is the most frequent form of
      nephrotic syndrome in childhood. In the glomerular basement membrane (GBM) of
      adult patients with MCNS, a reduced expression of a specific heparan sulphate
      (HS) domain has been reported. In children with MCNS, urinary activity of the HS
      degrading enzyme heparanase was increased. It is, therefore, possible that a
      decreased GBM HS expression is associated with the pathogenesis of proteinuria in
      patients with MCNS. METHODS: In this study, HS in glomeruli of five adult and six
      paediatric patients with MCNS were analysed by immunofluorescence staining using
      four different antibodies, each defining a specific sulphated HS domain. The
      pediatric patients were subdivided into three groups depending on the presence or
      absence of podocyte foot process effacement, the level of proteinuria and
      prednisone administration at the time of the biopsy. In addition, kidneys of rats
      with adriamycin nephropathy (ADRN), a model for MCNS, were included in the study.
      RESULTS: Expression of sulphated HS domains was not aberrant in adult or
      paediatric patients compared with control subjects. Children with and without
      proteinuria had the same HS content. In contrast, rats with ADRN showed a
      decreased glomerular expression of sulphated HS domains. CONCLUSIONS: These
      results suggest that in patients with MCNS proteinuria is not associated with
      major changes in glomerular expression of sulphated HS domains.

PMID- 17526542
TI  - No clear evidence of ACEi efficacy on the progression of chronic kidney disease
      in children with hypodysplastic nephropathy--report from the ItalKid Project
      database.
AB  - BACKGROUND: Chronic kidney diseases (CKD) tend to progress to end-stage renal
      failure (ESRF). As it has been demonstrated that angiotensin-converting enzyme
      inhibitors (ACEi) have a renoprotective effect in adults with proteinuric disease
      and may be effective in reducing hyperfiltration and proteinuria, they are also
      frequently used as anti-progression agents in paediatric patients with CKD
      despite the lack of data confirming their role in the nephropathies peculiar to
      children. The aim of this study was to investigate whether patients with
      hypodysplastic CKD (the most common cause of ESRF in children) treated with ACEi
      show a significantly slower decline in creatinine clearance (Ccr). METHODS: The
      analysis was based on the information available in the database of the ItalKid
      Project, a nationwide, population-based registry of chronic renal insufficiency
      (CRI) in children in Italy. Of the 822 patients with CRI due to hypodysplasia, we
      selected those who had been continuously treated with ACEi; the control patients
      were identified from the same diagnostic group and matched for gender, age and
      baseline Ccr. RESULTS: Progression was analysed as the slope of Ccr in a total of
      164 patients: 41 cases and 123 matched controls. There were no significant
      between-group differences in blood pressure, duration of follow-up or pre-study
      slope of Ccr (-0.31+/-2.26 vs -0.33+/-3.58 ml/min/1.73 m2/year; P=NS). After an
      average of 4.9+/-2.3 years, the mean slope of Ccr was 40% lower in the ACEi
      treated cases in comparison to controls (-1.08+/-2.08 vs -1.80+/-4.42 ml/min/1.73
      m2/year), however, this difference was not statistically significant (P=0.31).
      CONCLUSIONS: We conclude that ACEi treatment does not significantly modify the
      naturally progressive course of hypodysplastic nephropathy in children and
      further studies are necessary before such treatment is routinely proposed for
      anti-progression purposes in children with CKD.

PMID- 17526543
TI  - Mycophenolic acid (MPA) and its glucuronide metabolites interact with transport
      systems responsible for excretion of organic anions in the basolateral membrane
      of the human kidney.
AB  - BACKGROUND: Mycophenolic acid (MPA), the active moiety of the prodrug
      mycophenolate mofetil, is widely used in immunosuppressive regimens after kidney,
      liver or heart transplantation. MPA is metabolized predominantly to the inactive
      7-O-glucuronide (MPAG). A minor fraction is converted to the pharmacologically
      active acyl glucuronide (AcMPAG). All compounds ultimately are eliminated via the
      kidneys. Due to their structures, MPA and its metabolites are candidate
      substrates for the human organic anion transporters 1 (OAT1) and 3 (OAT3) as well
      as for the Na+-dicarboxylate cotransporter 3 (NaDC3). METHODS: Human (h)OAT1,
      hOAT3 and hNaDC3 were expressed from in vitro synthesized cRNA in collagenase
      defolliculated Xenopus laevis oocytes. On day 3 post-injection, measurements were
      made of (i) substrate-associated currents using MPA and MPAG (only in hNaDC3
      expressing oocytes) and (ii) uptake of [3H]p-aminohippurate (hOAT1) or
      [3H]estrone sulfate (hOAT3) in the absence or presence of either MPA, MPAG or
      AcMPAG. RESULTS: In hNaDC3-expressing oocytes at -60 mV, MPA (0.1 mM) as well as
      MPAG (0.1 mM) induced inward currents that were 17 and 25% of the currents evoked
      by succinate (1 mM). Vice versa, currents induced by succinate (1 mM) were
      partially inhibited by MPA and MPAG. hOAT1 and hOAT3 were potently inhibited by
      MPA (IC50 1.24 and 0.52 microM, respectively). Human OAT3, but not hOAT1, was
      additionally inhibited by both glucuronide metabolites of MPA in a concentration
      dependent manner (IC50 15.2 microM for MPAG and 2.88 microM for AcMPAG),
      consistent with a preference of hOAT3 for more bulky substrates compared with
      hOAT1. CONCLUSIONS: MPA and its metabolites potently interact with renal organic
      anion transporters hOAT1 and hOAT3, and thereby may interfere with the renal
      secretion of antiviral drugs, cortisol and other organic anions.

PMID- 17526544
TI  - Focal segmental glomerulosclerosis associated with long-term treatment with
      zoledronate in a myeloma patient.

PMID- 17526545
TI  - Maintaining control over haemoglobin levels: optimizing the management of anaemia
      in chronic kidney disease.
AB  - The introduction of erythropoiesis-stimulating agents radically advanced the
      management of anaemia associated with chronic kidney disease (CKD). The European
      Best Practice Guidelines recommend that most patients with CKD achieve a target
      haemoglobin (Hb) >/=11 g/dl to reduce the risk of adverse outcomes. The optimal
      upper Hb level has not been determined and will likely vary among CKD patient
      populations. Recently reported studies show evidence that normalising Hb (
      approximately 14 g/dl) in CKD may increase the risk of adverse events and puts
      attention to the importance of the upper Hb target. Most patients can achieve
      target Hb levels with proper treatment. However, recent studies have demonstrated
      that while average Hb levels may fall within desired targets, the Hb levels of
      many patients are not being adequately controlled, i.e. their Hb levels are not
      consistently maintained within a specified target range over time. Furthermore,
      data indicate that failing to control Hb levels over time may increase the risk
      of adverse outcomes, including mortality. This review will discuss the challenges
      in controlling Hb in the CKD patient population, particularly in haemodialysis
      patients. Factors that affect Hb control over time will be considered, as well as
      the clinical criteria for its assessment. Although challenging, control of Hb is
      manageable and has potential clinical benefits.

PMID- 17526546
TI  - Extended dosing intervals with erythropoiesis-stimulating agents in chronic
      kidney disease: a review of clinical data.
AB  - The recombinant human erythropoietins epoetins alfa and beta have relatively
      short half-lives ( approximately 24 h by subcutaneous route) and have
      traditionally been administered 2 or 3 times a week for the treatment of anaemia
      in patients with chronic kidney disease. However, multiple weekly injections are
      inconvenient for both the patient and the healthcare provider. With the
      introduction of the longer-acting erythropoiesis-stimulating agent darbepoetin
      alfa, there has been growing interest in longer dosing intervals for
      erythropoiesis-stimulating agents. Data from several randomized studies have
      shown that darbepoetin alfa is effective in maintaining haemoglobin levels when
      administered (subcutaneously, intravenously or both) every 2 weeks in dialysis
      patients, and every 2 weeks or monthly in patients with chronic kidney disease
      not yet receiving dialysis. Moreover, intravenous administration with darbepoetin
      alfa does not require a higher dosage compared with the subcutaneous route.
      Epoetins alfa and beta have also been studied in similar schedules, although few
      data from well-designed studies are available. Current data suggest that once
      weekly administration of these forms of epoetin is feasible in dialysis patients,
      but dose increases are often required when switching patients from traditional
      twice- or thrice-weekly schedules. Also, administration of epoetins every other
      week is feasible in selected patients with chronic renal insufficiency. Further
      study is required to clarify the optimum schedule for epoetins in these settings.

PMID- 17526547
TI  - Pharmacology of darbepoetin alfa.
AB  - The distinct molecular structure of darbepoetin alfa, in both its amino acid
      sequence and its carbohydrate content, results in a biologic profile with lower
      binding affinity, longer circulating half-life, and higher in vivo potency
      compared with the epoetins. The mechanisms responsible for these differences in
      biological effects have not been fully explained. Pharmacokinetic investigations
      of darbepoetin alfa using prolonged blood sampling times established that the
      mean terminal half-life after subcutaneous (SC) administration is 70 to 105
      hours. Pharmacodynamic studies were conducted to assess the suitability of
      darbepoetin alfa for use in weekly or less frequent (once every other week or
      once a month) dosing regimens to maintain haemoglobin levels in patients with
      anaemia of renal disease. Regardless of dialysis status, route of administration,
      or prior treatment with an erythropoiesis-stimulating agent, darbepoetin alfa
      administered at extended intervals was able to raise or maintain hemoglobin
      levels to target. More rigorous studies will be needed to confirm these findings.

PMID- 17526548
TI  - Development and exploitation of a clinical decision support system for the
      management of renal anaemia.
AB  - The management of renal disease and its comorbidities lends itself to the use of
      computer-assisted decision support systems (CDSS); however, several issues with
      regard to computer-based treatment algorithms remain unresolved. This review
      examines the development and application of a clinical decision support system
      for the management of renal anaemia. Studies illustrate the dependence of outcome
      on prespecified haemoglobin (Hb) intervention values (thresholds) and the use of
      a computer program containing treatment algorithms to manage Epoetin doses and
      iron supplements. Early experimental studies and randomized, controlled studies
      are discussed that examine the use of clinical measures of haemodialysis (HD) and
      peritoneal dialysis (PD), including Hb, serum ferritin and red cell hypochromia
      or transferrin saturation. Broad flexibility of erythropoietic agent, dosing,
      route of administration and frequency has been built into computer programs
      written for clinical and experimental application. While further studies with the
      system are anticipated, predictability and sustainability of Hb outcomes and a
      capacity to manage large patient groups have been demonstrated and wider
      application appears promising.

PMID- 17526549
TI  - Histopathological prevalence of subchondral insufficiency fracture of the femoral
      head.
AB  - OBJECTIVE: Subchondral insufficiency fracture of the femoral head (SIF) is a
      recently recognised cause of acute onset arthritis mostly in older women, which
      previously had been commonly considered either as osteonecrosis or
      osteoarthritis. The purpose of this study is to report the histopathological
      incidence of SIF using surgically removed femoral heads. METHODS: We reviewed
      7718 consecutive femoral heads from 7286 patients removed over a 4-year period
      (2001-2004). There were 4211 women and 3507 men. The age range was from 13 to 96,
      average age was 60. There were 7349 hips with a preoperative clinical diagnosis
      of osteoarthritis and 369 with a preoperative clinical diagnosis of
      osteonecrosis. RESULTS: SIF was diagnosed histologically as the primary process
      in 501 of 7718 resected femoral heads (6.5%). The age range in these patients was
      from 20 to 93, with an average age of 68, in which 79% (394 hips) were over 60.
      They were 305 hips in women and 196 in men. The affected side was the right one
      in 253 hips and left in 248. The prevalence of SIF in cases with a preoperative
      diagnosis of osteoarthritis was 6.3% (460 of 7349), and with osteonecrosis was
      11.1% (41 of 369). In all cases, callus and granulation tissue were observed
      histologically along the fracture line. CONCLUSIONS: In this large series of
      total hip replacements SIF as the cause of disease was diagnosed histologically
      in 6.5% of the surgically removed femoral heads.

PMID- 17526550
TI  - Fibronectin gene polymorphisms are associated with the development of B-cell
      lymphoma in type II mixed cryoglobulinemia.
AB  - OBJECTIVE: To analyse fibronectin (FN) gene polymorphisms in type II mixed
      cryoglobulinemic syndrome (MCsn), an immune-complex mediated systemic vasculitis
      linked to hepatitis C virus (HCV) infection and characterised by rheumatoid
      factor (RF) positive B-cell proliferation at high risk for the progression into
      non-Hodgkin's lymphoma (NHL). METHODS: Samples from 74 patients with MCsn (type
      II serum cryoglobulins and clinical signs of vasculitis) were studied. In all, 58
      (78.4%) patients were HCV-positive. In total, 21 (28.4%) patients developed a B
      cell NHL during the course of MCsn. A total of 72 patients with HCV-negative and
      MC-unrelated NHL and 110 healthy blood donors (HBDs) were taken as controls.
      HaeIIIb and MspI FN gene polymorphisms were analysed by PCR and specific
      restriction enzyme digestions, following reported procedures. Plasma FN levels
      were analysed by ELISA, whenever possible. RESULTS: HaeIIIb and MspI allele and
      genotype frequencies did not differ between MCsn patients and HBDs. Of note, the
      DD-MspI (OR = 5.99; CI 1.77-20.261, p = 0.0039) and the AA-HaeIIIb (OR = 4.82, CI
      1.42-16.39, p = 0.0176) homozygosis appeared significantly associated with the
      development of B-cell NHL in MCsn patients, with the HaeIIIb A allele possibly
      conferring an increased risk of NHL in the general population (OR = 1.72, CI
      1.128-2.635, p = 0.0133). None of the other MCsn-related clinical manifestations
      were significantly associated with a particular genetic pattern. No association
      between FN plasma levels and FN genotypes was found. CONCLUSION: Genotyping for
      MspI and HaeIIIb FN gene polymorphisms may be clinically relevant to define the
      risk of lymphoma development in MCsn.

PMID- 17526551
TI  - MRI of enthesitis of the appendicular skeleton in spondyloarthritis.
AB  - Entheses are sites where tendons, ligaments, joint capsules or fascia attach to
      bone. Inflammation of the entheses (enthesitis) is a well-known hallmark of
      spondyloarthritis (SpA). As entheses are associated with adjacent, functionally
      related structures, the concepts of an enthesis organ and functional entheses
      have been proposed. This is important in interpreting imaging findings in
      entheseal-related diseases. Conventional radiographs and CT are able to depict
      the chronic changes associated with enthesitis but are of very limited use in
      early disease. In contrast, MRI is sensitive for detecting early signs of
      enthesitis and can evaluate both soft-tissue changes and intraosseous
      abnormalities of active enthesitis. It is therefore useful for the early
      diagnosis of enthesitis-related arthropathies and monitoring therapy. Current
      knowledge and typical MRI features of the most commonly involved entheses of the
      appendicular skeleton in patients with SpA are reviewed. The MRI appearances of
      inflammatory and degenerative enthesopathy are described. New options for imaging
      enthesitis, including whole-body MRI and high-resolution microscopy MRI, are
      briefly discussed.

PMID- 17526552
TI  - Phenotypical and functional characteristics of in vitro expanded bone marrow
      mesenchymal stem cells from patients with systemic sclerosis.
AB  - BACKGROUND: Mesenchymal stem cells (MSCs) have a potential immunomodulatory role
      in autoimmune disease; however, the qualitative properties and haematopoietic
      support capacity of MSCs derived from patients with autoimmune disease is
      unclear. OBJECTIVES: To further characterise phenotypically and functionally bone
      marrow (BM)-derived MSCs from patients with systemic sclerosis (SSc). METHODS:
      Key parameters of BM-derived MSC function and phenotype were assessed in 12
      patients with SSc and compared with 13 healthy normal controls. The parameters
      included the ability to: form colony-forming unit fibroblasts (CFU-F),
      differentiate along the adipogenic and osteogenic lineages, express cell surface
      antigens defining the MSCs population, support normal haematopoiesis and suppress
      in vitro lymphocyte proliferation induced by either anti-CD3epsilon plus anti
      CD28 monoclonal antibodies or the mixed lymphocyte reaction. RESULTS: SSc MSCs
      were shown to have a similar characteristic phenotype, capacities to form CFU-F
      and to differentiate along adipogenic and osteogenic lineages as those of healthy
      donor MSCs. The ability of SSc MSCs to support long-term haematopoiesis was also
      identical to that of controls. Both healthy donor and SSc BM MSCs reduced the
      proliferation of autologous and allogeneic peripheral blood mononuclear cells in
      a cell number dependent fashion. CONCLUSIONS: These results show that BM-derived
      MSCs from patients with SSc under the described culture conditions exhibit the
      same phenotypic, proliferative, differentiation potential and immunosuppressive
      properties as their healthy counterparts and could therefore be considered in an
      autologous setting. Further studies are needed to ensure the quality and safety
      of large-scale expansion of patient MSCs prior to their potential use in clinical
      trials.

PMID- 17526553
TI  - Physical work and chronic shoulder disorder. Results of a prospective population
      based study.
AB  - OBJECTIVES: A study of whether occupational physical load predicted subsequent
      chronic shoulder disorders. METHODS: A comprehensive national survey was carried
      out among a representative sample (n = 7217) of the Finnish adult population in
      1977-80. Twenty years later, 1286 participants from the previous survey were
      invited to be re-examined, and 909 (71%) participated. After excluding those with
      diagnosed shoulder disorders at baseline, 883 subjects were available for the
      analyses. RESULTS: At follow-up, a physician diagnosed chronic shoulder disorders
      in 63 subjects (7%) using a standardised protocol. Work exposure to repetitive
      movements and vibration at baseline increased the risk of shoulder disorder:
      adjusted ORs 2.3 (95% CI 1.3 to 4.1) and 2.5 (1.2 to 5.2), respectively. Exposure
      to several physical factors increased the risk further, the adjusted OR was
      nearly 4 for at least three exposures. The adverse effects of physical work were
      seen even among those older than 75 years at follow-up. The statistically
      significant risk factors differed between genders: for men vibration and
      repetitive movements, and for women lifting heavy loads and working in awkward
      postures. Age and body mass index modified the effects of the physical exposures.
      The results remained similar after excluding those with any shoulder pain at
      baseline. CONCLUSIONS: This is the first prospective study in a general
      population showing that occupational physical loading increases the risk of a
      subsequent clinical shoulder disorder and the effects seem to be long-term. Early
      preventive measures at the workplace may have long-lasting health benefits for
      the shoulder.

PMID- 17526554
TI  - Long-term follow-up results after autologous haematopoietic stem cell
      transplantation for severe systemic sclerosis.
AB  - OBJECTIVE: Systemic sclerosis (SSc) is a generalised autoimmune disease, causing
      morbidity and a reduced life expectancy, especially in patients with rapidly
      progressive diffuse cutaneous SSc. As no proven treatment exists, autologous
      haematopoietic stem cell transplantation (HSCT) is employed as a new therapeutic
      strategy in patients with a poor prognosis. This study reports the effects on
      survival, skin and major organ function of HSCT in patients with severe diffuse
      cutaneous SSc. PATIENTS AND METHODS: A total of 26 patients were evaluated.
      Peripheral blood stem cells were collected using cyclophosphamide (4 g/m2) and
      rHu G-CSF (5 to 10 microg/kg/day) and were reinfused after positive CD34+
      selection. For conditioning, cyclophosphamide 200 mg/kg was used. RESULTS: After
      a median follow-up of 5.3 (1-7.5) years, 81% (n = 21/26) of the patients
      demonstrated a clinically beneficial response. The Kaplan-Meier estimated
      survival at 5 years was 96.2% (95% CI 89-100%) and at 7 years 84.8% (95% CI 70.2
      100%) and event-free survival, defined as survival without mortality, relapse or
      progression of SSc, resulting in major organ dysfunction was 64.3% (95% CI 47.9
      86%) at 5 years and 57.1% (95% CI 39.3-83%) at 7 years. CONCLUSION: This study
      confirms that autologous HSCT in selected patients with severe diffuse cutaneous
      SSc results in sustained improvement of skin thickening and stabilisation of
      organ function up to 7 years after transplantation.

PMID- 17526555
TI  - High anti-cyclic citrullinated peptide levels and an algorithm of four variables
      predict radiographic progression in patients with rheumatoid arthritis: results
      from a 10-year longitudinal study.
AB  - OBJECTIVES: New effective therapies with particularly good effect on joint
      destruction have highlighted the need for reliable predictors of radiographic
      progression in rheumatoid arthritis (RA). Our objective was to assess the
      combined predictive role of a set of laboratory markers with regard to 10-year
      radiographic progression, and to examine the effect of anti-cyclic citrullinated
      peptide (anti-CCP) level. METHODS: A cohort of 238 patients with RA was followed
      longitudinally for 10 years with the collection of clinical data and serum
      samples. 125 patients with radiographs of the hands available at both baseline
      and after 10 years were included in this study. Radiographs were scored according
      to the van der Heijde modified Sharp score. Baseline sera were analysed for C
      reactive protein, erythrocyte sedimentation rate (ESR), anti-CCP, IgA rheumatoid
      factor (RF) and IgM RF. Logistic regression analyses were used to identify
      predictors of radiographic progression and to examine the effect of anti-CCP
      level. RESULTS: Anti-CCP (OR 4.0; 95% CI 1.6 to 10.0) was the strongest
      independent predictor of radiographic progression. Female gender (OR 3.3; 95% CI
      1.3 to 7.6), high ESR (OR 3.2; 95% CI 1.2 to 7.6) and a positive IgM RF (OR 3.1;
      95% CI 1.2 to 7.9) were also independent predictors. Compared with the anti-CCP
      negative patients, patients with low to moderate levels of anti-CCP (OR 2.6; 95%
      CI 0.9 to 7.2) and patients with high levels of anti-CCP (OR 9.9; 95% CI 2.7 to
      36.7) were more likely to develop radiographic progression. CONCLUSIONS: Anti
      CCP, IgM RF, ESR and female gender were independent predictors of radiographic
      progression and could be combined into an algorithm for better prediction.
      Patients with high levels of anti-CCP were especially prone to radiographic
      progression, indicating that the anti-CCP level may add prognostic information.

PMID- 17526556
TI  - Chronic ethanol increases fetal cerebral blood flow specific to the ethanol
      sensitive cerebellum under normoxaemic, hypercapnic and acidaemic conditions:
      ovine model.
AB  - Cerebral hypoxia has been proposed as a mechanism by which prenatal ethanol
      exposure causes fetal alcohol spectrum disorder (FASD) in children, but no study
      had tested this hypothesis using a chronic exposure model that mimicks a common
      human exposure pattern. Pregnant sheep were exposed to ethanol, 0.75 or 1.75 g
      kg(-1) (to create blood ethanol concentrations of 85 and 185 mg dl(-1),
      respectively), or saline 3 days per week in succession (a 'binge drinking' model)
      from gestational day (GD) 109 until GD 132. Fetuses were instrumented on GD 119
      120 and studied on GD 132. The 1.75 g kg(-1) dose resulted in a significant
      increase in fetal biventricular output (measured by radiolabelled microsphere
      technique) and heart rate, and a reduction of mean arterial pressure and total
      peripheral resistance at 1 h, the end of ethanol infusion. The arterial partial
      pressure of CO(2) was increased, arterial pH was decreased and arterial partial
      pressure of O(2) did not change. Fetal whole-brain blood flow increased by 37%
      compared with the control group at 1 h, resulting in increased cerebral oxygen
      delivery. The elevation in brain blood flow was region specific, occurring
      preferentially in the ethanol-sensitive cerebellum, increasing by 44% compared
      with the control group at 1 h. There were no changes in the lower dose group.
      Assessment of regional differences in the teratogenic effects of ethanol by
      stereological cell-counting technique showed a reduced number of cerebellar
      Purkinje cells in response to the 1.75 g kg(-1) dose compared with the control
      brains. However, no such differences in neuronal numbers were observed in the
      hippocampus or the olfactory bulb. We conclude that repeated exposure to moderate
      doses of ethanol during the third trimester alters fetal cerebral vascular
      function and increases blood flow in brain regions that are vulnerable to ethanol
      in the presence of acidaemia and hypercapnia, and in the absence of hypoxia.

PMID- 17526557
TI  - Peripheral 5-HT1A receptors are not essential for increased ventilation evoked by
      systemic 8-OH-DPAT challenge in anaesthetized rats.
AB  - The respiratory effects resulting from stimulation of 5-HT(1A) receptors were
      studied in spontaneously breathing rats that were: (i) neurally intact and
      subsequently bilaterally vagotomized; (ii) subjected to bilateral midcervical
      vagotomy followed by supranodosal vagotomy; (iii) midcervically vagotomized and
      treated by carotid sinus/body denervation; or (iv) subjected to infra- and
      supranodosal vagotomy followed by pharmacological blockade of 5-HT(1A) receptors.
      An intravenous bolus of the 5-HT(1A) receptor agonist 8-hydroxy
      dipropylaminotetralin (8-OH-DPAT, 10 microg kg(-1)) evoked increases in both
      breathing rate and tidal volume. After section of the midcervical and
      supranodosal vagi, 8-OH-DPAT challenge still increased the respiratory rate and
      tidal volume. Carotid sinus/body denervation did not reduce the augmentation of
      the tidal volume, but prevented the increase in breathing rate. Blockade of 5
      HT(1A) receptors with intravenous doses of 1-(2-metoxyphenyl)-4-[4-(2
      phthalimido) butyl] piperazine (NAN 190; 20 microg kg(-1)) abolished all
      respiratory effects of 8-OH-DPAT challenge. In all the neural states, 8-OH-DPAT
      evoked a significant fall in mean arterial blood pressure. Pretreatment with NAN
      190 reduced baseline values of mean arterial pressure and prevented 8-OH-DPAT
      induced hypotension. These results indicate that: (i) 8-OH-DPAT-evoked activation
      of 5-HT(1A) receptors increases breathing rate and tidal volume, which persists
      after section of the lung vagi and the nodose ganglia, but only the increase in
      breathing rate was abolished by carotid sinus/body denervation; and (ii) 8-OH
      DPAT hyperventilatory and hypotensive responses result from the excitation of
      presumed 5-HT(1A) carotid receptors and the central 5-HT(1A)-expressing neurones.

PMID- 17526558
TI  - Uniaxial stretch-induced regulation of mitogen-activated protein kinase, Akt and
      p70 S6 kinase in the ageing Fischer 344 x Brown Norway rat aorta.
AB  - The effects of ageing on the cardiovascular system contribute to substantial
      alterations in cellular morphology and function. The variables regulating these
      changes are unknown; however, one set of signalling molecules that may be of
      particular importance in mediating numerous cellular responses, including control
      of cell growth, differentiation and adaptation, are the proteins associated with
      the mitogen-activated protein kinase (MAPK) signalling systems. The MAPKs, in
      conjunction with the p70 S6k signalling cascade, have emerged as critical
      components for regulating numerous mechanotransduction-related cellular
      responses. Here we investigate the ability of uniaxial stretch to activate the
      MAPK and p70 S6k pathways in adult (6-month-old), aged (30-month-old) and very
      aged (36-month-old) Fischer 344/NNiaHSd x Brown Norway/BiNia (FBN) rats. Western
      blotting of the MAPK family proteins extracellular signal-regulated kinase (Erk)
      1/2, p38- and c-Jun NH(2)-terminal kinase (Jnk)-MAPKs showed differential
      expression and activation between these proteins with age. An acute 15 min
      interval of 20% uniaxial stretch using an ex vivo aortic preparation demonstrated
      similar regulation of Erk1/2, p38- and Jnk-MAPK. However, ageing altered uniaxial
      induced p70 S6k pathway signalling. These observations confirm previous data
      demonstrating that MAPK proteins are mechanically regulated and also suggest that
      p70 S6k signalling expression and activation are controlled differently with
      ageing. Taken together, these data may help to explain, in part, the age-related
      changes in vascular morphology, function and response to injury.

PMID- 17526559
TI  - The protonation state of the Glu-71/Asp-80 residues in the KcsA potassium
      channel: a first-principles QM/MM molecular dynamics study.
AB  - Although a few x-ray structures of the KcsA K(+) channel have been crystallized
      several issues concerning the mechanisms of the ionic permeation and the
      protonation state of the selectivity filter ionizable side chains are still open.
      Using a first-principles quantum mechanical/molecular mechanical simulation
      approach, we have investigated the protonation state of Glu-71 and Asp-80, two
      important residues located in the vicinity of the selectivity filter. Results
      from the dynamics show that a proton is shared between the two residues, with a
      slight preference for Glu-71. The proton is found to exchange on the picosecond
      timescale, an interesting phenomenon that cannot be observed in classical
      molecular dynamics. Simulations of different ionic loading states of the filter
      show that the probability for the proton transfer is correlated with the filter
      occupancy. In addition, the Glu-71/Asp-80 pair is able to modulate the potential
      energy profile experienced by a K(+) ion as it translates along the pore axis.
      These theoretical predictions, along with recent experimental results, suggest
      that changes of the filter structure could be associated with a shift in the Glu
      Asp protonation state, which in turn would influence the ion translocation.

PMID- 17526560
TI  - Influence of the environment and probes on rapid DNA sequencing via transverse
      electronic transport.
AB  - We study theoretically the feasibility of using transverse electronic transport
      within a nanopore for rapid DNA sequencing. Specifically, we examine the effects
      of the environment and detection probes on the distinguishability of the DNA
      bases. We find that the intrinsic measurement bandwidth of the electrodes helps
      the detection of single bases by averaging over the current distributions of each
      base. We also find that although the overall magnitude of the current may change
      dramatically with different detection conditions, the intrinsic
      distinguishability of the bases is not significantly affected by pore size and
      transverse field strength. The latter is the result of very effective
      stabilization of the DNA by the transverse field induced by the probes, so long
      as that field is much larger than the field that drives DNA through the pore. In
      addition, the ions and water together effectively screen the charge on the
      nucleotides, so that the electron states participating in the transport
      properties of the latter ones resemble those of the uncharged species. Finally,
      water in the environment has negligible direct influence on the transverse
      electrical current.

PMID- 17526561
TI  - Flexibility in HIV-1 assembly subunits: solution structure of the monomeric C
      terminal domain of the capsid protein.
AB  - The protein CA forms the mature capsid of human immunodeficiency virus.
      Hexamerization of the N-terminal domain and dimerization of the C-terminal
      domain, CAC, occur during capsid assembly, and both domains constitute potential
      targets for anti-HIV inhibitors. CAC homodimerization occurs mainly through its
      second helix, and is abolished when its sole tryptophan is mutated to alanine.
      Previous thermodynamic data obtained with the dimeric and monomeric forms of CAC
      indicate that the structure of the mutant resembles that of a monomeric
      intermediate found in the folding and association reactions of CAC. We have
      solved the three-dimensional structure in aqueous solution of the monomeric
      mutant. The structure is similar to that of the subunits in the dimeric,
      nonmutated CAC, except the segment corresponding to the second helix, which is
      highly dynamic. At the end of this region, the polypeptide chain is bent to bury
      several hydrophobic residues and, as a consequence, the last two helices are
      rotated 90 degrees when compared to their position in dimeric CAC. The previously
      obtained thermodynamic data are consistent with the determined structure of the
      monomeric mutant. This extraordinary ability of CAC to change its structure may
      contribute to the different modes of association of CA during HIV assembly, and
      should be taken into account in the design of new drugs against this virus.

PMID- 17526562
TI  - Conformational dynamics in loop swap mutants of homologous fibronectin type III
      domains.
AB  - Fibronectin type III (FN-III) domains are autonomously folded modules found in a
      variety of multidomain proteins. The 10th FN-III domain from fibronectin (fnFN10)
      and the 3rd FN-III domain from tenascin-C (tnFN3) have 27% sequence identity and
      the same overall fold; however, the CC' loop has a different pattern of backbone
      hydrogen bonds and the FG loop is longer in fnFN10 compared to tnFN3. To examine
      the influence of length, sequence, and context in determining dynamical
      properties of loops, CC' and FG loops were swapped between fnFN10 and tnFN3 to
      generate four mutant proteins and backbone conformational dynamics on ps-ns and
      mus-ms timescales were characterized by solution (15)N-NMR spin relaxation
      spectroscopy. The grafted loops do not strongly perturb the properties of the
      protein scaffold; however, specific effects of the mutations are observed for
      amino acids that are proximal in space to the sites of mutation. The amino acid
      sequence primarily dictates conformational dynamics when the wild-type and
      grafted loop have the same length, but both sequence and context contribute to
      conformational dynamics when the loop lengths differ. The results suggest that
      changes in conformational dynamics of mutant proteins must be considered in both
      theoretical studies and protein design efforts.

PMID- 17526563
TI  - The thermodynamic meaning of metabolic exchange fluxes.
AB  - Metabolic flux analysis (MFA) deals with the experimental determination of steady
      state fluxes in metabolic networks. An important feature of the (13)C MFA method
      is its capability to generate information on both directions of bidirectional
      reaction steps given by exchange fluxes. The biological interpretation of these
      exchange fluxes and their relation to thermodynamic properties of the respective
      reaction steps has never been systematically investigated. As a central result,
      it is shown here that for a general class of enzyme reaction mechanisms the
      quotients of net and exchange fluxes measured by (13)C MFA are coupled to Gibbs
      energies of the reaction steps. To establish this relation the concept of
      apparent flux ratios of enzymatic isotope-labeling networks is introduced and
      some computing rules for these flux ratios are given. Application of these rules
      reveals a conceptional pitfall of (13)C MFA, which is the inherent dependency of
      measured exchange fluxes on the chosen tracer atom. However, it is shown that
      this effect can be neglected for typical biochemical reaction steps under
      physiological conditions. In this situation, the central result can be formulated
      as a two-sided inequality relating fluxes, pool sizes, and standard Gibbs
      energies. This relation has far-reaching consequences for metabolic flux
      analysis, quantitative metabolomics, and network thermodynamics.

PMID- 17526564
TI  - Dynamics of magnetotactic bacteria in a rotating magnetic field.
AB  - The dynamics of the motile magnetotactic bacterium Magnetospirillum
      gryphiswaldense in a rotating magnetic field is investigated experimentally and
      analyzed by a theoretical model. These elongated bacteria are propelled by single
      flagella at each bacterial end and contain a magnetic filament formed by a linear
      assembly of approximately 40 ferromagnetic nanoparticles. The movements of the
      bacteria in suspension are analyzed by consideration of the orientation of their
      magnetic dipoles in the field, the hydrodynamic resistance of the bacteria, and
      the propulsive force of the flagella. Several novel features found in experiments
      include a velocity reversal during motion in the rotating field and an
      interesting diffusive wandering of the trajectory curvature centers. A new method
      to measure the magnetic moment of an individual bacterium is proposed based on
      the theory developed.

PMID- 17526565
TI  - Biophysical mechanisms of transient optical stimulation of peripheral nerve.
AB  - A new method for in vivo neural activation using low-intensity, pulsed infrared
      light exhibits advantages over standard electrical means by providing contact
      free, spatially selective, artifact-free stimulation. Here we investigate the
      biophysical mechanism underlying this phenomenon by careful examination of
      possible photobiological effects after absorption-driven light-tissue
      interaction. The rat sciatic nerve preparation was stimulated in vivo with a
      Holmium:yttrium aluminum garnet laser (2.12 microm), free electron laser (2.1
      microm), alexandrite laser (750 nm), and prototype solid-state laser nerve
      stimulator (1.87 microm). We systematically determined relative contributions
      from a list of plausible interaction types resulting in optical stimulation,
      including thermal, pressure, electric field, and photochemical effects.
      Collectively, the results support our hypothesis that direct neural activation
      with pulsed laser light is induced by a thermal transient. We then present data
      that characterize and quantify the spatial and temporal nature of this required
      temperature rise, including a measured surface temperature change required for
      stimulation of the peripheral nerve (6 degrees C-10 degrees C). This interaction
      is a photothermal effect from moderate, transient tissue heating, a temporally
      and spatially mediated temperature gradient at the axon level (3.8 degrees C-6.4
      degrees C), resulting in direct or indirect activation of transmembrane ion
      channels causing action potential generation.

PMID- 17526566
TI  - Static light scattering from concentrated protein solutions, I: General theory
      for protein mixtures and application to self-associating proteins.
AB  - Exact expressions for the static light scattering of a solution containing up to
      three species of point-scattering solutes in highly nonideal solutions at
      arbitrary concentration are obtained from multicomponent scattering theory.
      Explicit expressions for thermodynamic interaction between solute molecules,
      required to evaluate the scattering relations, are obtained using an equivalent
      hard particle approximation similar to that employed earlier to interpret
      scattering of a single protein species at high concentration. The dependence of
      scattering intensity upon total protein concentration is calculated for mixtures
      of nonassociating proteins and for a single self-associating protein over a range
      of concentrations up to 200 g/l. An approximate semiempirical analysis of the
      concentration dependence of scattering intensity is proposed, according to which
      the contribution of thermodynamic interaction to scattering intensity is modeled
      as that of a single average hard spherical species. Simulated data containing
      pseudo-noise comparable in magnitude to actual experimental uncertainty are
      modeled using relations obtained from the proposed semiempirical analysis. It is
      shown that by using these relations one can extract from the data reasonably
      reliable information about underlying weak associations that are manifested only
      at very high total protein concentration.

PMID- 17526567
TI  - Determination of the contribution of the myristoyl group and hydrophobic amino
      acids of recoverin on its dynamics of binding to lipid monolayers.
AB  - It has been postulated that myristoylation of peripheral proteins would
      facilitate their binding to membranes. However, the exact involvement of this
      lipid modification in membrane binding is still a matter of debate. Proteins
      containing a Ca(2+)-myristoyl switch where the extrusion of their myristoyl group
      is dependent on calcium binding is best illustrated by the Ca(2+)-binding
      recoverin, which is present in retinal rod cells. The parameters responsible for
      the modulation of the membrane binding of recoverin are still largely unknown.
      This study was thus performed to determine the involvement of different
      parameters on recoverin membrane binding. We have used surface pressure
      measurements and PM-IRRAS spectroscopy to monitor the adsorption of myristoylated
      and nonmyristoylated recoverin onto phospholipid monolayers in the presence and
      absence of calcium. The adsorption curves have shown that the myristoyl group and
      hydrophobic residues of myristoylated recoverin strongly accelerate membrane
      binding in the presence of calcium. In the case of nonmyristoylated recoverin in
      the presence of calcium, hydrophobic residues alone are responsible for its much
      faster monolayer binding than myristoylated and nonmyristoylated recoverin in the
      absence of calcium. The infrared spectra revealed that myristoylated and
      nonmyristoylated recoverin behave very different upon adsorption onto
      phospholipid monolayers. Indeed, PM-IRRAS spectra indicated that the myristoyl
      group allows a proper orientation and organization as well as faster and stronger
      binding of myristoylated recoverin to lipid monolayers compared to
      nonmyristoylated recoverin. Simulations of the spectra have allowed us to
      postulate that nonmyristoylated recoverin changes conformation and becomes
      hydrated at large extents of adsorption as well as to estimate the orientation of
      myristoylated recoverin with respect to the monolayer plane. In addition,
      adsorption measurements and electrophoresis of trypsin-treated myristoylated
      recoverin in the presence of zinc or calcium demonstrated that recoverin has a
      different conformation but a similar extent of monolayer binding in the presence
      of such ions.

PMID- 17526568
TI  - Zn2+ sensitivity of high- and low-voltage activated calcium channels.
AB  - The essential cation zinc (Zn2+) blocks voltage-dependent calcium channels in
      several cell types, which exhibit different sensitivities to Zn2+. The
      specificity of the Zn2+ effect on voltage-dependent calcium channel subtypes has
      not been systematically investigated. In this study, we used a transient protein
      expression system to determine the Zn2+ effect on low- and high-voltage activated
      channels. We found that in Ba2+, the IC50 value of Zn2+ was alpha1-subunit
      dependent with lowest value for CaV1.2, and highest for CaV3.1; the sensitivity
      of the channels to Zn2+ was approximately ranked as
      CaV1.2>CaV3.2>CaV2.3>CaV2.2=CaV 2.1>or=CaV3.3=CaV3.1. Although the CaV2.2 and
      CaV3.1 channels had similar IC50 for Zn2+ in Ba2+, the CaV2.2, but not CaV3.1
      channels, had approximately 10-fold higher IC50 to Zn2+ in Ca2+. The reduced
      sensitivity of CaV2.2 channels to Zn2+ in Ca2+ was partially reversed by
      disrupting a putative EF-hand motif located external to the selectivity filter
      EEEE locus. Thus, our findings support the notion that the Zn2+ block, mediated
      by multiple mechanisms, may depend on conformational changes surrounding the
      alpha1 pore regions. These findings provide fundamental insights into the
      mechanism underlying the inhibitory effect of zinc on various Ca2+ channel
      subtypes.

PMID- 17526569
TI  - Mechanical properties of collagen fibrils.
AB  - The formation of collagen fibers from staggered subfibrils still lacks a
      universally accepted model. Determining the mechanical properties of single
      collagen fibrils (diameter 50-200 nm) provides new insights into collagen
      structure. In this work, the reduced modulus of collagen was measured by
      nanoindentation using atomic force microscopy. For individual type 1 collagen
      fibrils from rat tail, the modulus was found to be in the range from 5 GPa to
      11.5 GPa (in air and at room temperature). The hypothesis that collagen
      anisotropy is due to the subfibrils being aligned along the fibril axis is
      supported by nonuniform surface imprints performed by high load nanoindentation.

PMID- 17526570
TI  - R-92L and R-92W mutations in cardiac troponin T lead to distinct energetic
      phenotypes in intact mouse hearts.
AB  - It is now known that the flexibility of the troponin T (TnT) tail determines thin
      filament conformation and hence cross-bridge cycling properties, expanding the
      classic structural role of TnT to a dynamic role regulating sarcomere function.
      Here, using transgenic mice bearing R-92W and R-92L missense mutations in cardiac
      TnT known to alter the flexibility of the TnT tropomyosin-binding domain, we
      found mutation-specific differences in the cost of contraction at the whole heart
      level. Compared to age- and gender-matched sibling hearts, mutant hearts
      demonstrate greater ATP utilization measured using (31)P NMR spectroscopy as
      decreases in [ATP] and [PCr] and |DeltaG(~ATP)| at all workloads and profound
      systolic and diastolic dysfunction at all energetic states. R-92W hearts showed
      more severe energetic abnormalities and greater contractile dysfunction than R
      92L hearts. The cost of increasing contraction was abnormally high when [Ca(2+)]
      was used to increase work in mutant hearts but was normalized with supply of the
      beta-adrenergic agonist dobutamine. These results show that R-92L and R-92W
      mutations in the TM-binding domain of cardiac TnT alter thin filament structure
      and flexibility sufficiently to cause severe defects in both whole heart
      energetics and contractile performance, and that the magnitude of these changes
      is mutation specific.

PMID- 17526571
TI  - Steric selectivity in Na channels arising from protein polarization and mobile
      side chains.
AB  - Monte Carlo simulations of equilibrium selectivity of Na channels with a DEKA
      locus are performed over a range of radius R and protein dielectric coefficient
      epsilon(p). Selectivity arises from the balance of electrostatic forces and
      steric repulsion by excluded volume of ions and side chains of the channel
      protein in the highly concentrated and charged (approximately 30 M) selectivity
      filter resembling an ionic liquid. Ions and structural side chains are described
      as mobile charged hard spheres that assume positions of minimal free energy.
      Water is a dielectric continuum. Size selectivity (ratio of Na+ occupancy to K+
      occupancy) and charge selectivity (Na+ to Ca2+) are computed in concentrations as
      low as 10(-5) M Ca2+. In general, small R reduces ion occupancy and favors Na+
      over K+ because of steric repulsion. Small epsilon(p) increases occupancy and
      favors Na+ over Ca2+ because protein polarization amplifies the pore's net
      charge. Size selectivity depends on R and is independent of epsilon(p); charge
      selectivity depends on both R and epsilon(p). Thus, small R and epsilon(p) make
      an efficient Na channel that excludes K+ and Ca2+ while maximizing Na+ occupancy.
      Selectivity properties depend on interactions that cannot be described by
      qualitative or verbal models or by quantitative models with a fixed free energy
      landscape.

PMID- 17526572
TI  - Antifreeze proteins at the ice/water interface: three calculated discriminating
      properties for orientation of type I proteins.
AB  - Antifreeze proteins (AFPs) protect many plants and organisms from freezing in low
      temperatures. Of the different AFPs, the most studied AFP Type I from winter
      flounder is used in the current computational studies to gain molecular insight
      into its adsorption at the ice/water interface. Employing molecular dynamics
      simulations, we calculate the free energy difference between the hydrophilic and
      hydrophobic faces of the protein interacting with ice. Furthermore, we identify
      three properties of Type I "antifreeze" proteins that discriminate among these
      two orientations of the protein at the ice/water interface. The three properties
      are: the "surface area" of the protein; a measure of the interaction of the
      protein with neighboring water molecules as determined by the number of hydrogen
      bond count, for example; and the side-chain orientation angles of the threonine
      residues. All three discriminants are consistent with our free energy results,
      which clearly show that the hydrophilic protein face orientations toward the
      ice/water interface, as hypothesized from experimental and ice/vacuum
      simulations, are incorrect and support the hypothesis that the hydrophobic face
      is oriented toward the ice/water interface. The adsorption free energy is
      calculated to be 2-3 kJ/mol.

PMID- 17526573
TI  - Force-response considerations in ciliary mechanosensation.
AB  - Considerable experimental evidence indicates that the primary, nonmotile cilium
      is a mechanosensory organelle in several epithelial cell types. As the
      relationship between cellular responses and nature and magnitude of applied
      forces is not well understood, we have investigated the effects of exposure of
      monolayers of renal collecting duct chief cells to orbital shaking and quantified
      the forces incident on cilia. An exposure of 24 h of these cells to orbital
      shaking resulted in a decrease of amiloride-sensitive sodium current by
      approximately 60% and ciliary length by approximately 30%. The sensitivity of the
      sodium current to shaking was dependent on intact cilia. The drag force on cilia
      due to induced fluid flow during orbital shaking was estimated at maximally
      5.2x10(-3) pN at 2 Hz, approximately 4 times that of thermal noise. The major
      structural feature of cilia contributing to their sensitivity appears to be
      ciliary length. As more than half of the total drag force is exerted on the
      ciliary cap, one function of the slender stalk may be to expose the cap to
      greater drag force. Regardless, the findings indicate that the cilium is a
      mechanosensory organelle with a sensitivity much lower than previously
      recognized.

PMID- 17526574
TI  - Competing docking interactions can bring about bistability in the MAPK cascade.
AB  - Mitogen-activated protein kinases are crucial regulators of various cell fate
      decisions including proliferation, differentiation, and apoptosis. Depending on
      the cellular context, the Raf-Mek-Erk mitogen-activated protein kinase cascade
      responds to extracellular stimuli in an all-or-none manner, most likely due to
      bistable behavior. Here, we describe a previously unrecognized positive-feedback
      mechanism that emerges from experimentally observed sequestration effects in the
      core Raf-Mek-Erk cascade. Unphosphorylated/monophosphorylated Erk sequesters Mek
      into Raf-inaccessible complexes upon weak stimulation, and thereby inhibits
      cascade activation. Mek, once phosphorylated by Raf, triggers Erk
      phosphorylation, which in turn induces dissociation of Raf-inaccessible Mek-Erk
      heterodimers, and thus further amplifies Mek phosphorylation. We show that this
      positive circuit can bring about bistability for parameter values measured
      experimentally in living cells. Previous studies revealed that bistability can
      also arise from enzyme depletion effects in the Erk double (de)phosphorylation
      cycle. We demonstrate that the feedback mechanism proposed in this article
      synergizes with such enzyme depletion effects to bring about a much larger
      bistable range than either mechanism alone. Our results show that stable docking
      interactions and competition effects, which are common in protein kinase
      cascades, can result in sequestration-based feedback, and thus can have profound
      effects on the qualitative behavior of signaling pathways.

PMID- 17526575
TI  - The acacia gum arabinogalactan fraction is a thin oblate ellipsoid: a new model
      based on small-angle neutron scattering and ab initio calculation.
AB  - Acacia gum is a branched complex polysaccharide whose main chain consists of 1,3
      linked beta-D-galactopyranosyl units. Acacia gum is defined as a
      heteropolysaccharide since it contains approximately 2% of a polypeptide. The
      major molecular fraction (F1) accounting for approximately 88% of the total
      acacia gum mass is an arabinogalactan peptide with a weight-average molecular
      weight of 2.86 x 10(5) g/mol. The molecular structure of F1 is actually unknown.
      From small angle neutron scattering experiments in charge screening conditions,
      F1 appeared to be a dispersion of two-dimensional structures with a radius of
      gyration of approximately 6.5 nm and an inner dense branched structure. Inverse
      Fourier transform of F1 scattering form factor revealed a disk-like morphology
      with a diameter of approximately 20 nm and a thickness below 2 nm. Ab initio
      calculations on the pair distance distribution function produced a porous oblate
      ellipsoid particle with a central intricated "network". Both transmission
      electron microscopy and atomic force microscopy confirm the thin disk model and
      structural dimensions. The model proposed is a breakthrough in the field of
      arabinogalactan-protein-type macromolecules. In particular, concerning the site
      of biosynthesis of these macromolecules, the structural dimensions found in this
      study would be in agreement with a phloem-mediated long-distance transport. In
      addition, the structure of F1 could also explain the low viscosity of acacia gum
      solutions, and its ability to self-assemble and to interact with proteins.

PMID- 17526576
TI  - Elastic properties of viruses.
AB  - Viruses are compact biological nanoparticles whose elastic and dynamical
      properties are hardly known. Inelastic (Brillouin) light scattering was used to
      characterize these properties, from microcrystals of the Satellite Tobacco Mosaic
      Virus, a nearly spherical plant virus of 17-nm diameter. Longitudinal sound
      velocities in wet and dry Satellite Tobacco Mosaic Virus crystals were determined
      and compared to that of the well-known protein crystal, lysozyme. Localized
      vibrational modes of the viral particles (i.e., particle modes) were sought in
      the relevant frequency ranges, as derived assuming the viruses as full free
      nanospheres. Despite very favorable conditions, regarding virus concentration and
      expected low damping in dry microcrystals, no firm evidence of virus particle
      modes could be detected.

PMID- 17526577
TI  - Effects of cholesterol on dry bilayers: interactions between phosphatidylcholine
      unsaturation and glycolipid or free sugar.
AB  - Cholesterol and other sterols are important components of biological membranes
      and are known to strongly influence the physical characteristics of lipid
      bilayers. Although this has been studied extensively in fully hydrated membranes,
      little is known about the effects of cholesterol on the stability of membranes in
      the dry state. Here, we present a Fourier transform infrared spectroscopy study
      on the effects of cholesterol on the phase behavior of dry liposomes composed of
      phosphatidylcholines with different degrees of fatty acid unsaturation or of
      mixtures of phosphatidylcholine with a plant galactolipid. In addition, we have
      analyzed the H-bonding of cholesterol, galactose, and a combination of the two
      additives to the P=O and C=O groups in dry phosphatidylcholine bilayers. The data
      indicate a complex balance of interactions between the different components in
      the dry state and a strong influence of fatty acid unsaturation on the
      interactions of the diacyl lipids with both cholesterol and galactose.

PMID- 17526578
TI  - A kinetic model of single and clustered IP3 receptors in the absence of Ca2+
      feedback.
AB  - Ca2+ liberation through inositol 1,4,5-trisphosphate receptor (IP3R) channels
      generates complex patterns of spatiotemporal cellular Ca2+ signals owing to the
      biphasic modulation of channel gating by Ca2+ itself. These processes have been
      extensively studied in Xenopus oocytes, where imaging studies have revealed local
      Ca2+ signals ("puffs") arising from clusters of IP3R, and patch-clamp studies on
      isolated oocyte nuclei have yielded extensive data on IP3R gating kinetics. To
      bridge these two levels of experimental data, we developed an IP3R model and
      applied stochastic simulation and transition matrix theory to predict the
      behavior of individual and clustered IP3R channels. The channel model consists of
      four identical, independent subunits, each of which has an IP3-binding site
      together with one activating and one inactivating Ca2+-binding site. The channel
      opens when at least three subunits undergo a conformational change to an "active"
      state after binding IP3 and Ca2+. The model successfully reproduces patch-clamp
      data; including the dependence of open probability, mean open duration, and mean
      closed duration on [IP3] and [Ca2+]. Notably, the biexponential distribution of
      open-time duration and the dependence of mean open time on [Ca2+] are explained
      by populations of openings involving either three or four active subunits. As a
      first step toward applying the single IP3R model to describe cellular responses,
      we then simulated measurements of puff latency after step increases of [IP3].
      Assuming that stochastic opening of a single IP3R at basal cytosolic [Ca2+] and
      any given [IP3] has a high probability of rapidly triggering neighboring channels
      by calcium-induced calcium release to evoke a puff, optimal correspondence with
      experimental data of puff latencies after photorelease of IP3 was obtained when
      the cluster contained a total of 40-70 IP3Rs.

PMID- 17526579
TI  - Establishing a definitive stoichiometry for the Na+/monocarboxylate cotransporter
      SMCT1.
AB  - Several different stoichiometries have been proposed for the
      Na(+)/monocarboxylate cotransporter SMCT1, including variable Na(+)/substrate
      stoichiometry. In this work, we have definitively established an invariant 2:1
      cotransport stoichiometry for SMCT1. By using two independent means of assay, we
      first showed that SMCT1 exhibits a 2:1 stoichiometry for Na(+)/lactate
      cotransport. Radiolabel uptake experiments proved that, unlike lactate, propionic
      acid diffuses passively through oocyte membranes and, consequently, propionate is
      a poor candidate for stoichiometric determination by these methods. Although we
      previously determined SMCT1 stoichiometry by measuring reversal potentials, this
      technique produced erroneous values, because SMCT1 simultaneously mediates both
      an inwardly rectifying cotransport current and an outwardly rectifying anionic
      leak current; the leak current predominates in the range where reversal
      potentials are observed. We therefore employed a method that compared the effect
      of halving the external Na(+) concentration to the effect of halving the external
      substrate concentration on zero-current potentials. Both lactate and propionate
      were cotransported through SMCT1 using 2:1 stoichiometries. The leak current
      passing through the protein has a 1 osmolyte/charge stoichiometry. Identification
      of cotransporter stoichiometry is not always a trivial task and it can lead to a
      much better understanding of the transport activity mediated by the protein in
      question.

PMID- 17526580
TI  - Models of beta-amyloid ion channels in the membrane suggest that channel
      formation in the bilayer is a dynamic process.
AB  - Here we model the Alzheimer beta-peptide ion channel with the goal of obtaining
      insight into the mechanism of amyloid toxicity. The models are built based on NMR
      data of the oligomers, with the universal U-shaped (strand-turn-strand) motif.
      After 30-ns simulations in the bilayer, the channel dimensions, shapes and
      subunit organization are in good agreement with atomic force microscopy (AFM).
      The models use the Abeta(17-42) pentamer NMR-based coordinates. Extension and
      bending of the straight oligomers lead to two channel topologies, depending on
      the direction of the curvature: 1), the polar/charged N-terminal beta-strand of
      Abeta(17-42) faces the water-filled pore, and the hydrophobic C-terminal beta
      strand faces the bilayer (CNpNC; p for pore); and 2), the C-terminal beta-strand
      faces the solvated pore (NCpCN). In the atomistic simulations in a fully solvated
      DOPC lipid bilayer, the first (CNpNC) channel preserves the pore and conducts
      solvent; by contrast, hydrophobic collapse blocks the NCpCN channel. AFM
      demonstrated open pores and collapsed complexes. The final averaged CNpNC pore
      dimensions (outer diameter 8 nm; inner diameter approximately 2.5 nm) are in the
      AFM range (8-12 nm; approximately 2 nm, respectively). Further, in agreement with
      high-resolution AFM images, during the simulations, the channels spontaneously
      break into ordered subunits in the bilayer; however, we also observe that the
      subunits are loosely connected by partially disordered inner beta-sheet,
      suggesting subunit mobility in the bilayer. The cationic channel has strong
      selective affinity for Ca(2+), supporting experimental calcium-selective beta
      amyloid channels. Membrane permeability and consequent disruption of calcium
      homeostasis were implicated in cellular degeneration. Consequently, the CNpNC
      channel topology can sign cell death, offering insight into amyloid toxicity via
      an ion "trap-release" transport mechanism. The observed loosely connected subunit
      organization suggests that amyloid channel formation in the bilayer is a dynamic,
      fluid process involving subunit association, dissociation, and channel
      rearrangements.

PMID- 17526581
TI  - Quantitative characterization of intrinsic disorder in polyglutamine: insights
      from analysis based on polymer theories.
AB  - Intrinsically disordered proteins (IDPs) are unfolded under physiological
      conditions. Here we ask if archetypal IDPs in aqueous milieus are best described
      as swollen disordered coils in a good solvent or collapsed disordered globules in
      a poor solvent. To answer this question, we analyzed data from molecular
      simulations for a 20-residue polyglutamine peptide and concluded, in accord with
      experimental results, that water is a poor solvent for this system. The relevance
      of monomeric polyglutamine is twofold: It is an archetypal IDP sequence and its
      aggregation is associated with nine neurodegenerative diseases. The main advance
      in this work lies in our ability to make accurate assessments of solvent quality
      from analysis of simulations for a single, rather than multiple chain lengths. We
      achieved this through the proper design of simulations and analysis of order
      parameters that are used to describe conformational equilibria in polymer physics
      theories. Despite the preference for collapsed structures, we find that
      polyglutamine is disordered because a heterogeneous ensemble of conformations of
      equivalent compactness is populated at equilibrium. It is surprising that water
      is a poor solvent for polar polyglutamine and the question is: why? Our
      preliminary analysis suggests that intrabackbone interactions provide at least
      part of the driving force for the collapse of polyglutamine in water. We also
      show that dynamics for conversion between distinct conformations resemble
      structural relaxation in disordered, glassy systems, i.e., the energy landscape
      for monomeric polyglutamine is rugged. We end by discussing generalizations of
      our methods to quantitative studies of conformational equilibria of other low
      complexity IDP sequences.

PMID- 17526582
TI  - Cholesterol displacement from membrane phospholipids by hexadecanol.
AB  - Adding cholesterol to monolayers of certain phospholipids drives the separation
      of liquid-ordered from liquid-disordered domains. The ordered phases appear to
      contain stoichiometric complexes of cholesterol and phospholipid. Furthermore, it
      has been suggested that the cholesterol in these complexes has a low chemical
      activity compared to that of the free sterol; i.e., that in excess of the
      phospholipid binding capacity. We have now tested the hypothesis that the
      membrane intercalator 1-hexadecanol (HD) similarly associates with phospholipids
      and thereby displaces the complexed cholesterol. HD introduced into monolayers of
      pure dimyristoylphosphatidylcholine generated highly condensed (stable and solid)
      domains. In contrast, the phase behavior of mixed monolayers of the phospholipid,
      sterol, and alcohol suggested that HD could substitute for cholesterol mole for
      mole in promoting liquid-ordered domains. We also found that the transfer of
      cholesterol from mixed monolayers to aqueous cyclodextrin was greatly stimulated
      by the presence of HD, but only at levels sufficient to competitively displace
      the sterol from the phospholipid. This enhanced efflux was interpreted to reflect
      an increase in uncomplexed cholesterol. We conclude that HD forms complexes with
      dimyristoylphosphatidylcholine that are surprisingly similar to those of
      cholesterol. HD competitively displaces cholesterol from the phospholipid and
      thereby increases its chemical activity.

PMID- 17526583
TI  - Nanometer distance measurements in RNA using site-directed spin labeling.
AB  - The method of site-directed spin labeling (SDSL) utilizes a stable nitroxide
      radical to obtain structural and dynamic information on biomolecules. Measuring
      dipolar interactions between pairs of nitroxides yields internitroxide distances,
      from which quantitative structural information can be derived. This study
      evaluates SDSL distance measurements in RNA using a nitroxide probe, designated
      as R5, which is attached in an efficient and cost-effective manner to backbone
      phosphorothioate sites that are chemically substituted in arbitrary sequences. It
      is shown that R5 does not perturb the global structure of the A-form RNA helix.
      Six sets of internitroxide distances, ranging from 20 to 50 A, were measured on
      an RNA duplex with a known X-ray crystal structure. The measured distances
      strongly correlate (R(2) = 0.97) with those predicted using an efficient
      algorithm for determining the expected internitroxide distances from the parent
      RNA structure. The results enable future studies of global RNA structures for
      which high-resolution structural data are absent.

PMID- 17526584
TI  - Nucleotide effects on the structure and dynamics of actin.
AB  - Adenosine 5'-triphosphate or ATP is the primary energy source within the cell,
      releasing its energy via hydrolysis into adenosine 5'-diphosphate or ADP. Actin
      is an important ATPase involved in many aspects of cellular function, and the
      binding and hydrolysis of ATP regulates its polymerization into actin filaments
      as well as its interaction with a host of actin-associated proteins. Here we
      study the dynamics of monomeric actin in ATP, ADP-Pi, and ADP states via
      molecular dynamics simulations. As observed in some crystal structures we see
      that the DNase-I loop is an alpha-helix in the ADP state but forms an
      unstructured coil domain in the ADP-Pi and ATP states. We also find that this
      secondary structure change is reversible, and by mimicking nucleotide exchange we
      can observe the transition between the helical and coil states. Apart from the
      DNase-I loop, we also see several key structural differences in the nucleotide
      binding cleft as well as in the hydrophobic cleft between subdomains 1 and 3
      where WH2-containing proteins have been shown to interact. These differences
      provide a structural basis for understanding the observed differences between the
      various nucleotide states of actin and provide some insight into how ATP
      regulates the interaction of actin with itself and other proteins.

PMID- 17526585
TI  - HIV-1 fusion peptide decreases bending energy and promotes curved fusion
      intermediates.
AB  - A crucial step in human immunodeficiency virus (HIV) infection is fusion between
      the viral envelope and the T-cell membrane, which must involve intermediate
      membrane states with high curvature. Our main result from diffuse x-ray
      scattering is that the bending modulus K(C) is greatly reduced upon addition of
      the HIV fusion peptide FP-23 to lipid bilayers. A smaller bending modulus reduces
      the free energy barriers required to achieve and pass through the highly curved
      intermediate states and thereby facilitates fusion and HIV infection. The
      reduction in K(C) is by a factor of 13 for the thicker, stiffer 1,2-sn
      dierucoylphosphatidylcholine bilayers and by a factor of 3 for 1,2-sn
      dioleoylphosphatidylcholine bilayers. The reduction in K(C) decays exponentially
      with concentration of FP-23, and the 1/e concentration is <1 mol % peptide/lipid,
      which is well within the physiological range for a fusion site. A secondary
      result is, when FP-23 is added to the samples which consist of stacks of
      membranes, that the distance between membranes increases and eventually becomes
      infinite at full hydration (unbinding); we attribute this both to electrostatic
      repulsion of the positively charged arginine in the FP-23 and to an increase in
      the repulsive fluctuation interaction brought about by the smaller K(C). Although
      this latter interaction works against membrane fusion, our results show that the
      energy that it requires of the fusion protein machinery to bring the HIV envelope
      membrane and the target T-cell membrane into close contact is negligible.

PMID- 17526586
TI  - Detection and correction of blinking bias in image correlation transport
      measurements of quantum dot tagged macromolecules.
AB  - Semiconductor nanocrystals or quantum dots (QDs) are becoming widely used as
      fluorescent labels for biological applications. Here we demonstrate that
      fluorescence fluctuation analysis of their diffusional mobility using temporal
      image correlation spectroscopy is highly susceptible to systematic errors caused
      by fluorescence blinking of the nanoparticles. Temporal correlation analysis of
      fluorescence microscopy image time series of streptavidin-functionalized
      (CdSe)ZnS QDs freely diffusing in two dimensions shows that the correlation
      functions are fit well to a commonly used diffusion decay model, but the
      transport coefficients can have significant systematic errors in the measurements
      due to blinking. Image correlation measurements of the diffusing QD samples
      measured at different laser excitation powers and analysis of computer simulated
      image time series verified that the effect we observe is caused by fluorescence
      intermittency. We show that reciprocal space image correlation analysis can be
      used for mobility measurements in the presence of blinking emission because it
      separates the contributions of fluctuations due to photophysics from those due to
      transport. We also demonstrate application of the image correlation methods for
      measurement of the diffusion coefficient of glycosyl phosphatidylinositol
      anchored proteins tagged with QDs as imaged on living fibroblasts.

PMID- 17526587
TI  - Effect of cholesterol on the biophysical and physiological properties of a
      clinical pulmonary surfactant.
AB  - Pulmonary surfactant is a complex mixture of lipids and proteins that forms a
      surface-active film at the air-water interface of alveoli capable of reducing
      surface tension to near 0 mN/m. The role of cholesterol, the major neutral lipid
      component of pulmonary surfactant, remains uncertain. We studied the
      physiological effect of cholesterol by monitoring blood oxygenation levels of
      surfactant-deficient rats treated or not treated with bovine lipid extract
      surfactant (BLES) containing zero or physiological amounts of cholesterol. Our
      results indicate no significant difference between BLES and BLES containing
      cholesterol immediately after treatment; however, during ventilation, BLES
      treated animals maintained higher PaO2 values compared to BLES+cholesterol
      treated animals. We used a captive bubble tensiometer to show that physiological
      amounts of cholesterol do not have a detrimental effect on the surface activity
      of BLES at 37 degrees C. The effect of cholesterol on topography and lateral
      organization of BLES Langmuir-Blodgett films was also investigated using atomic
      force microscopy. Our data indicate that cholesterol induces the formation of
      domains within liquid-ordered domains (Lo). We used time-of-flight-secondary ion
      mass spectrometry and principal component analysis to show that cholesterol is
      concentrated in the Lo phase, where it induces structural changes.

PMID- 17526588
TI  - Dynamical control of the shape and size of stereocilia and microvilli.
AB  - We discuss theoretically the shape of actin-based protrusions such as stereocilia
      or microvilli that have important functions in many biological systems. These
      linear protrusions are dynamical structures continuously renewed by treadmilling:
      actin polymerizes at the tip of the cilium and depolymerizes in its bulk. They
      also often have a well-controlled length such as in the hair bundles of the inner
      ear cells where they appear in a graded staircase structure. Recent experimental
      results by another group of researchers show that the treadmilling velocity of
      the hair cell stereocilia is proportional to their length. We use generic
      arguments to describe the physics of stereocilia taking into account the effect
      of many individual proteins at a coarse-grained level by a few phenomenological
      parameters. At the tip of the cilium, we find that actin polymerization induces
      an effective pressure. Below the tip, the shape of the cilium is determined by
      depolymerization: Agreement with the observed shape requires that
      depolymerization occurs at least in two steps. Under these conditions, we
      calculate the cilium shape and provide physical grounds for the proportionality
      between treadmilling velocity and cilium length. We also calculate the
      penetration of the stereocilium in the actin cortical layer.

PMID- 17526589
TI  - Mixing of exciton and charge-transfer states in Photosystem II reaction centers:
      modeling of Stark spectra with modified Redfield theory.
AB  - We propose an exciton model for the Photosystem II reaction center (RC) based on
      a quantitative simultaneous fit of the absorption, linear dichroism, circular
      dichroism, steady-state fluorescence, triplet-minus-singlet, and Stark spectra
      together with the spectra of pheophytin-modified RCs, and so-called RC5 complexes
      that lack one of the peripheral chlorophylls. In this model, the excited state
      manifold includes a primary charge-transfer (CT) state that is supposed to be
      strongly mixed with the pure exciton states. We generalize the exciton theory of
      Stark spectra by 1), taking into account the coupling to a CT state (whose static
      dipole cannot be treated as a small parameter in contrast to usual excited
      states); and 2), expressing the line shape functions in terms of the modified
      Redfield approach (the same as used for modeling of the linear responses). This
      allows a consistent modeling of the whole set of experimental data using a
      unified physical picture. We show that the fluorescence and Stark spectra are
      extremely sensitive to the assignment of the primary CT state, its energy, and
      coupling to the excited states. The best fit of the data is obtained supposing
      that the initial charge separation occurs within the special-pair PD1PD2.
      Additionally, the scheme with primary electron transfer from the accessory
      chlorophyll to pheophytin gave a reasonable quantitative fit. We show that the
      effectiveness of these two pathways is strongly dependent on the realization of
      the energetic disorder. Supposing a mixed scheme of primary charge separation
      with a disorder-controlled competition of the two channels, we can explain the
      coexistence of fast sub-ps and slow ps components of the Phe-anion formation as
      revealed by different ultrafast spectroscopic techniques.

PMID- 17526590
TI  - Depth-resolved measurement of transient structural changes during action
      potential propagation.
AB  - We report noncontact optical measurement of fast transient structural changes in
      the crustacean nerve during action potential propagation without the need for
      exogenous chemicals or reflection coatings. The technique, spectral domain
      optical coherence tomography, provides real-time cross-sectional images of the
      nerve with micron-scale resolution to select a specific region for functional
      assessment and interferometric phase sensitivity for subnanometer-scale motion
      detection. Noncontact optical measurements demonstrate nanometer-scale transient
      movement on a 1-ms timescale associated with action potential propagation in
      crayfish and lobster nerves.

PMID- 17526591
TI  - Tether extrusion from red blood cells: integral proteins unbinding from
      cytoskeleton.
AB  - We investigate the mechanical strength of adhesion and the dynamics of detachment
      of the membrane from the cytoskeleton of red blood cells (RBCs). Using
      hydrodynamical flows, we extract membrane tethers from RBCs locally attached to
      the tip of a microneedle. We monitor their extrusion and retraction dynamics
      versus flow velocity (i.e., extrusion force) over successive extrusion-retraction
      cycles. Membrane tether extrusion is carried out on healthy RBCs and ATP-depleted
      or -inhibited RBCs. For healthy RBCs, extrusion is slow, constant in velocity,
      and reproducible through several extrusion-retraction cycles. For ATP-depleted or
      -inhibited cells, extrusion dynamics exhibit an aging phenomenon through
      extrusion-retraction cycles: because the extruded membrane is not able to retract
      properly onto the cell body, each subsequent extrusion exhibits a loss of
      resistance to tether growth over the tether length extruded at the previous
      cycle. In contrast, the additionally extruded tether length follows healthy
      dynamics. The extrusion velocity L depends on the extrusion force f according to
      a nonlinear fashion. We interpret this result with a model that includes the
      dynamical feature of membrane-cytoskeleton association. Tether extrusion leads to
      a radial membrane flow from the cell body toward the tether. In a distal
      permeation regime, the flow passes through the integral proteins bound to the
      cytoskeleton without affecting their binding dynamics. In a proximal sliding
      regime, where membrane radial velocity is higher, integral proteins can be torn
      out, leading to the sliding of the membrane over the cytoskeleton. Extrusion
      dynamics are governed by the more dissipative permeation regime: this leads to an
      increase of the membrane tension and a narrowing of the tether, which explains
      the power law behavior of L(f). Our main result is that ATP is necessary for the
      extruded membrane to retract onto the cell body. Under ATP depletion or
      inhibition conditions, the aging of the RBC after extrusion is interpreted as a
      perturbation of membrane-cytoskeleton linkage dynamics.

PMID- 17526593
TI  - Improving life sciences information retrieval using semantic web technology.
AB  - The ability to retrieve relevant information is at the heart of every aspect of
      research and development in the life sciences industry. Information is often
      distributed across multiple systems and recorded in a way that makes it difficult
      to piece together the complete picture. Differences in data formats, naming
      schemes and network protocols amongst information sources, both public and
      private, must be overcome, and user interfaces not only need to be able to tap
      into these diverse information sources but must also assist users in filtering
      out extraneous information and highlighting the key relationships hidden within
      an aggregated set of information. The Semantic Web community has made great
      strides in proposing solutions to these problems, and many efforts are underway
      to apply Semantic Web techniques to the problem of information retrieval in the
      life sciences space. This article gives an overview of the principles underlying
      a Semantic Web-enabled information retrieval system: creating a unified
      abstraction for knowledge using the RDF semantic network model; designing
      semantic lenses that extract contextually relevant subsets of information; and
      assembling semantic lenses into powerful information displays. Furthermore,
      concrete examples of how these principles can be applied to life science problems
      including a scenario involving a drug discovery dashboard prototype called
      BioDash are provided.

PMID- 17526594
TI  - Equitable utilisation of Indian community based health insurance scheme among its
      rural membership: cluster randomised controlled trial.
AB  - OBJECTIVE: To evaluate alternative strategies for improving the uptake of
      benefits of a community based health insurance scheme by its poorest members.
      DESIGN: Prospective cluster randomised controlled trial. SETTING: Self Employed
      Women's Association (SEWA) community based health insurance scheme in rural
      India. Participants 713 claimants at baseline (2003) and 1440 claimants two years
      later among scheme members in 16 rural sub-districts. INTERVENTIONS: After sales
      service with supportive supervision, prospective reimbursement, both packages,
      and neither package, randomised by sub-district. MAIN OUTCOME MEASURES: The
      primary outcome was socioeconomic status of claimants relative to members living
      in the same sub-district. Secondary outcomes were enrolment rates in SEWA
      Insurance, mean socioeconomic status of the insured population relative to the
      general rural population, and rate of claim submission. RESULTS: Between 2003 and
      2005, the mean socioeconomic status of SEWA Insurance members (relative to the
      rural population of Gujarat) increased significantly. Rates of claims also
      increased significantly, on average by 21.6 per 1000 members (P<0.001). However,
      differences between the intervention groups and the standard scheme were not
      significant. No systematic effect of time or interventions on the socioeconomic
      status of claimants relative to members in the same sub-district was found.
      CONCLUSIONS: Neither intervention was sufficient to ensure that the poorer
      members in each sub-district were able to enjoy the greater share of the scheme
      benefits. Claim submission increased as a result of interventions that seem to
      have strengthened awareness of and trust in a community based health insurance
      scheme. Trial registration Clinical trials NCT00421629.

PMID- 17526595
TI  - Hyperproliferative apoptosis-resistant endothelial cells in idiopathic pulmonary
      arterial hypertension.
AB  - Idiopathic pulmonary arterial hypertension (IPAH) is characterized by plexiform
      vascular lesions, which are hypothesized to arise from deregulated growth of
      pulmonary artery endothelial cells (PAEC). Here, functional and molecular
      differences among PAEC derived from IPAH and control human lungs were evaluated.
      Compared with control cells, IPAH PAEC had greater cell numbers in response to
      growth factors in culture due to increased proliferation as determined by
      bromodeoxyuridine incorporation and Ki67 nuclear antigen expression and decreased
      apoptosis as determined by caspase-3 activation and TdT-mediated dUTP nick end
      labeling assay. IPAH cells had greater migration than control cells but less
      organized tube formation in in vitro angiogenesis assay. Persistent activation of
      signal transducer and activator of transcription 3 (STAT3), a regulator of cell
      survival and angiogenesis, and increased expression of its downstream prosurvival
      target, Mcl-1, were identified in IPAH PAEC. A Janus kinase (JAK) selective
      inhibitor reduced STAT3 activation and blocked proliferation of IPAH cells.
      Phosphorylated STAT3 was detected in endothelial cells of IPAH lesions in vivo,
      suggesting that STAT3 activation plays a role in the proliferative pulmonary
      vascular lesions in IPAH lungs.

PMID- 17526596
TI  - A tissue-engineered model of fetal distal lung tissue.
AB  - In extending our previous studies toward development of an engineered distal lung
      tissue construct (M. J. Mondrinos, S. Koutzaki, E. Jiwanmall, M. Li, J. P.
      Dechadarevian, P. I. Lelkes, and C. M. Finck. Tissue Eng 12: 717-728, 2006), we
      studied the effects of exogenous fibroblast growth factors FGF10, FGF7, and FGF2
      on mixed populations of embryonic day 17.5 murine fetal pulmonary cells cultured
      in three-dimensional collagen gels. The morphogenic effects of the FGFs alone and
      in various combinations were assessed by whole mount immunohistochemistry and
      confocal microscopy. FGF10/7 significantly increased epithelial budding and
      proliferation; however, only FGF10 alone induced widespread budding. FGF7 alone
      induced dilation of epithelial structures but not widespread budding. FGF2 alone
      had a similar dilation, but not budding, effect in epithelial structures, and, in
      addition, significantly enhanced endothelial tubular morphogenesis and network
      formation, as well as mesenchymal proliferation. The combination of FGF10/7/2
      induced robust budding of epithelial structures and the formation of uniform
      endothelial networks in parallel. These data suggest that appropriate
      combinations of exogenous FGFs chosen to target specific FGF receptor isoforms
      will allow for control of lung epithelial and mesenchymal cell behavior in the
      context of an engineered system. We propose that tissue-engineered fetal distal
      lung constructs could provide a potential source of tissue or cells for lung
      augmentation in pediatric pulmonary pathologies, such as pulmonary hypoplasia and
      bronchopulmonary dysplasia. In addition, engineered systems will provide
      alternative in vitro venues for the study of lung developmental biology and
      pathobiology.

PMID- 17526597
TI  - Induction of cell cycle arrest and apoptosis by BCG infection in cultured human
      bronchial airway epithelial cells.
AB  - Bronchial airway epithelial cells (BAEpC) are among the first cells to encounter
      M. tuberculosis following airborne infection. However, the response of BAEpC to
      M. tuberculosis infection has been little studied. This study investigates the
      response of a human BAEpC cell line (BEAS-2B) to infection with Mycobacterium
      bovis Bacille Calmette Guerin (BCG). Cultured human BEAS-2B cells were
      experimentally infected with BCG. Uninfected BEAS-2B cultures were included as
      controls. Following infection, BEAS-2B cells were evaluated by various methods at
      various time points up to 3 days. Cell proliferation was evaluated by cellular
      bioreduction of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide
      assay. Distribution of cells along the cell cycle was evaluated by FACS analysis
      of cellular DNA. Apoptotic cells were identified by cell death ELISA and the
      terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling
      method. Eighty-four apoptosis-relevant genes were screened by PCR gene
      microarray. Translation of Fas, Fas ligand (Fas-L), and Fas-associated death
      domain (FADD) were evaluated quantitatively by real-time PCR. Expression of Fas
      and FADD proteins was evaluated by immunofluorescence and Western blot. Activity
      of caspase-3 and caspase-8 was evaluated by colorimetric assay of their enzymatic
      activity. BCG infection of BEAS-2B cells inhibits proliferation, induces cell
      cycle arrest at the G(0)/G(1) phase, causes apoptosis, modulates transcription of
      multiple apoptosis-relevant genes, promotes translation of Fas, Fas-L, and FADD,
      upregulates expression of Fas and FADD proteins, and increases activity of
      caspase-3 and caspase-8. Infection with BCG does not cause any significant change
      in the secretion of TGF-beta. The roles of Fas and FADD as mediators of BCG
      induced apoptosis in BEAS-2B cells were tested by partial blockade of Fas and
      FADD expression with silencing RNA. Partial blockade of Fas or FADD expression
      results in a decreased apoptotic response to BCG infection. In conclusion, BCG
      induces cell cycle arrest and apoptosis in BEAS-2B cells. BCG induced apoptosis
      of BEAS-2B cells via the Fas death receptor pathway.

PMID- 17526598
TI  - Heterogeneity of hypoxia-mediated decrease in I(K(V)) and increase in [Ca2+](cyt)
      in pulmonary artery smooth muscle cells.
AB  - Hypoxic pulmonary vasoconstriction is caused by a rise in cytosolic Ca(2+)
      ([Ca(2+)](cyt)) in pulmonary artery smooth muscle cells (PASMC) via multiple
      mechanisms. PASMC consist of heterogeneous phenotypes defined by contractility,
      proliferation, and apoptosis as well as by differences in expression and function
      of various genes. In rat PASMC, hypoxia-mediated decrease in voltage-gated K(+)
      (Kv) currents (I(K(V))) and increase in [Ca(2+)](cyt) were not uniformly
      distributed in all PASMC tested. Acute hypoxia decreased I(K(V)) and increased
      [Ca(2+)](cyt) in approximately 46% and approximately 53% of PASMC, respectively.
      Using combined techniques of single-cell RT-PCR and patch clamp, we show here
      that mRNA expression level of Kv1.5 in hypoxia-sensitive PASMC (in which hypoxia
      reduced I(K(V))) was much greater than in hypoxia-insensitive cells (in which
      hypoxia negligibly affected I(K(V))). These results demonstrate that 1) different
      PASMC express different Kv channel alpha- and beta-subunits, and 2) the
      sensitivity of a PASMC to acute hypoxia partially depends on the expression level
      of Kv1.5 channels; hypoxia reduces whole-cell I(K(V)) only in PASMC that express
      high level of Kv1.5. In addition, the acute hypoxia-mediated changes in
      [Ca(2+)](cyt) also vary in different PASMC. Hypoxia increases [Ca(2+)](cyt) only
      in 34% of cells tested, and the different sensitivity of [Ca(2+)](cyt) to hypoxia
      was not related to the resting [Ca(2+)](cyt). An intrinsic mechanism within each
      individual cell may be involved in the heterogeneity of hypoxia-mediated effect
      on [Ca(2+)](cyt) in PASMC. These data suggest that the heterogeneity of PASMC may
      partially be related to different expression levels and functional sensitivity of
      Kv channels to hypoxia and to differences in intrinsic mechanisms involved in
      regulating [Ca(2+)](cyt).

PMID- 17526599
TI  - Clara cells impact the pulmonary innate immune response to LPS.
AB  - Airway epithelial cells secrete proinflammatory mediators in response to LPS, but
      cytokine production by a prominent nonciliated bronchiolar epithelial cell, the
      Clara cell, specifically, is unknown. To investigate Clara cell cytokine
      production in response to LPS, we used a transformed murine Clara cell line, C22,
      and isolated Clara cells from C57Bl/6 mice. Stimulation of both cell types with
      LPS resulted in significant upregulation of keratinocyte-derived chemokine (KC)
      and monocyte chemoattractant protein-1, but did not induce TNF-alpha production.
      To determine whether LPS induces cytokine production by Clara cells in vivo, LPS
      was instilled intratracheally into mice. KC was expressed by Clara cells,
      alveolar type 2 cells, and alveolar macrophages, 2 h after LPS administration, as
      determined by in situ hybridization. TNF-alpha, although not expressed in airway
      epithelial cells, was expressed primarily in alveolar macrophages in response to
      LPS. To assess the impact of Clara cells on KC and TNF-alpha production in the
      lung in the early response to LPS, mice were treated with naphthalene to
      selectively induce Clara cell injury before LPS stimulation. KC expression in the
      airways and the lung periphery, and KC and TNF-alpha levels in the
      bronchoalveolar lavage fluid, were significantly reduced in naphthalene-treated
      vs. vehicle-treated mice after LPS stimulation. Furthermore, transwell cocultures
      of C22 cells and RAW264.7 macrophages indicated that C22 cells released a soluble
      factor(s) in response to LPS that enhanced macrophage production of TNF-alpha.
      These results indicate that Clara cells elaborate cytokines and modulate the lung
      innate immune response to LPS.

PMID- 17526600
TI  - A selective positive allosteric modulator of metabotropic glutamate receptor
      subtype 2 blocks a hallucinogenic drug model of psychosis.
AB  - Recent clinical studies reveal that selective agonists of group II metabotropic
      glutamate (mGlu) receptors have robust efficacy in treating positive and negative
      symptoms in patients with schizophrenia. Group II mGlu receptor agonists also
      modulate the in vivo activity of psychotomimetic drugs and reduce the ability of
      psychotomimetic hallucinogens to increase glutamatergic transmission. Because
      increased excitation of the medial prefrontal cortex (mPFC) has been implicated
      in pathophysiology of schizophrenia, the ability of group II mGlu receptor
      agonists to reduce hallucinogenic drug action in this region is believed to be
      directly related to their antipsychotic efficacy. A novel class of ligands,
      termed positive allosteric modulators, has recently been identified, displaying
      exceptional mGlu2 receptor selectivity. These compounds do not activate mGlu2
      receptors directly but potentiate the ability of glutamate and other agonists to
      activate this receptor. We now report that the mGlu2 receptor-selective positive
      allosteric modulator biphenyl-indanone A (BINA) modulates excitatory
      neurotransmission in the mPFC and attenuates the in vivo actions of the
      hallucinogenic 5-HT(2A/2C) receptor agonist (-)2,5-dimethoxy-4-bromoamphetamine
      [(-)DOB]. BINA attenuates serotonin-induced increases in spontaneous excitatory
      postsynaptic currents in the mPFC, mimicking the effect of the mGlu2/3 receptor
      agonist (2S,2'R,3'R)-2-(2',3'-dicarboxycyclopropyl)glycine (DCG-IV). In addition,
      BINA reduced (-)DOB-induced head twitch behavior and Fos expression in mPFC,
      effects reversed by pretreatment with the mGlu2/3 receptor antagonist 2S-2-amino
      2-(1S,2S-2-carboxycyclopropan-1-yl) -3 - (xanth-9-yl-)propionic acid (LY341495).
      These data confirm the relevance of excitatory signaling in the mPFC to the
      behavioral actions of hallucinogens and further support the targeting of mGlu2
      receptors as a novel strategy for treating glutamatergic dysfunction in
      schizophrenia.

PMID- 17526601
TI  - Contrast-enhanced ultrasound: an idea whose time has come.

PMID- 17526602
TI  - American Institute ofUltrasound in Medicine recommendations for contrast-enhanced
      liver ultrasound imaging clinical trials.

PMID- 17526603
TI  - Terminology for contrast-enhanced sonography: a practical glossary.
AB  - OBJECTIVE: The purpose of this glossary is to offer an updated guide to the
      correct terminology for contrast-enhanced sonography. METHODS: This report was
      prepared by a panel of radiologists from the Sonography Section of the Italian
      Association of Medical Radiology. A leading author prepared a list of terms based
      on a comprehensive literature survey. The draft was analyzed by 3 experts on the
      topic of contrast-enhanced sonography. These reviewers reached a consensus and
      prepared the final version. RESULTS: A list of 137 terms is included. These terms
      are briefly defined. Their proper application is discussed, with special
      reference to potential misleading uses. CONCLUSIONS: Contrast-enhanced sonography
      is a relatively new diagnostic tool, now entering clinical practice in several
      countries. Use of appropriate, universal terminology is mandatory in the
      scientific setting to allow comparison between different published experiences.
      Additionally, use of clear, standardized terminology is necessary in the clinical
      setting to facilitate report understanding by the referring physician.
      Standardized, nonequivocal nomenclature may also help future diffusion of
      sonographic contrast media in countries where their application is still not
      approved.

PMID- 17526604
TI  - Insonation of the eye in the presence of microbubbles: preliminary study of the
      duration and degree of vascular bioeffects--work in progress.
AB  - OBJECTIVE: The purpose of this study was to investigate the presence and duration
      of vascular permeability changes induced by the combination of ultrasound and an
      intravascular microbubble contrast agent in the rabbit eye. METHODS: Five eyes
      were studied in 8 anaesthetized rabbits. Insonation was performed with a
      diagnostic B-mode system (center frequency = 2 MHz; mechanical index [MI] = 0.2
      and 1.7) for 5 minutes after administration of perflutren microbubbles (0.07
      mL/kg). Fluorescein fundus angiography was performed before and 3 minutes after
      insonation; at 6 minutes, color fundus photography was used to assess the dye
      leakage, bleeding, and alteration of the diameter of fundus vessels. RESULTS:
      Alteration of fundus vessel diameters was observed in 1 of 5 cases at a low MI
      and in 4 of 5 cases at a higher MI. In 1 case, leakage of fluorescein indicated
      increased permeability at the higher MI. No bleeding was detected in any case.
      CONCLUSIONS: The permeability change induced by insonation and this dose of an
      ultrasound contrast agent appears to be transient under the conditions studied,
      although the time delay between insonation and optical assessment limits the
      completeness of the findings. This preliminary study may be relevant to drug
      delivery strategies using ultrasound and microbubbles.

PMID- 17526605
TI  - Parametric detection and measurement of perfusion defects in attenuated contrast
      echocardiographic images.
AB  - OBJECTIVE: Attenuation of radio frequency (RF) signals limits the use of contrast
      echocardiography. The harmonic-to-fundamental ratio (HFR) of the RF signals
      compensates for attenuation. We tested whether HFR analysis measures the left
      ventricular nonperfused area under simulated experimental attenuation. METHODS:
      Radio frequency image data from short axis systolic projections were obtained
      from 11 open-chest dogs with left anterior descending or left circumflex coronary
      artery occlusion followed by left atrial bolus injection of a perflutren
      microbubble contrast agent. Clinical attenuation was simulated by calibrated
      silicone pads interposed between the epicardial surface and the transducer to
      induce mild (7-dB) and severe (14-dB) reduction of the backscattered RF signals.
      Harmonic-to-fundamental ratio values were calculated for each image pixel for 0-,
      7-, and 14-dB attenuation conditions and reproducibly showed a "perfused area"
      and a "nonperfused area." A reference nonperfused area was obtained by manual
      delineation in high-quality contrast scans. RESULTS: Correlations of the HFR
      detected and manually outlined perfusion defect areas were R = 0.92 for 0 dB, R =
      0.94 for 7 dB, and R = 0.90 for 14 dB; the mean difference was less than 0.36
      cm(2) (negligible) in all 3 attenuation settings. Conclusions. Attenuation
      compensation by our HFR method allows precise measurement of myocardial perfusion
      defect areas in contrast scans with simulated high level of attenuation.

PMID- 17526606
TI  - Measuring tumor perfusion in control and treated murine tumors: correlation of
      microbubble contrast-enhanced sonography to dynamic contrast-enhanced magnetic
      resonance imaging and fluorodeoxyglucose positron emission tomography.
AB  - OBJECTIVE: The purpose of this study was to evaluate the ability of dynamic
      microbubble contrast-enhanced sonography (MCES), in comparison with dynamic
      contrast-enhanced magnetic resonance imaging (DCE-MRI) and fluorodeoxyglucose
      positron emission tomography (FDG-PET), to quantitatively characterize tumor
      perfusion in implanted murine tumors before and after treatment with a variety of
      regimens. METHODS: Seventeen mice with Lewis lung carcinoma implants were
      categorized to control, radiation therapy alone, antiangiogenic chemotherapy
      alone, and combined chemoradiation. On day 0 of each treatment regimen, MCES and
      DCE-MRI of each tumor were performed. On day 5 of treatment, dynamic FDG-PET,
      MCES, and DCE-MRI were performed. RESULTS: Microbubble contrast-enhanced
      sonography showed that intratumoral perfusion, blood volume, and blood velocity
      were highest in the untreated control group and successively lower in each of the
      treatment groups: radiation therapy alone resulted in a two-thirds reduction of
      perfusion; antiangiogenic chemotherapy resulted in a relatively larger reduction;
      and combined chemoradiotherapy resulted in the largest reduction. Microbubble
      contrast-enhanced sonography revealed longitudinal decreases in tumor perfusion,
      blood volume, and microvascular velocity over the 5-day course of
      chemoradiotherapy (all P < .01); conversely, these values rose significantly for
      the untreated control tumors (P < .01). Dynamic contrast-enhanced MRI showed a
      smaller and statistically insignificant average decrease in relative tumor
      perfusion for treated tumors. Dynamic PET revealed delayed uptake of FDG in the
      tumors that underwent chemoradiotherapy. CONCLUSIONS: Microbubble contrast
      enhanced sonography is an effective tool in the noninvasive, quantitative,
      longitudinal characterization of neovascularization in murine tumor models and is
      correlative with DCE-MRI and FDG-PET. Microbubble contrast-enhanced sonography
      has considerable potential in the clinical assessment of tumor neovascularization
      and in the assessment of the response to treatment.

PMID- 17526607
TI  - Contrast-enhanced ultrasonography for assessment of tumor vascularity in
      hepatocellular carcinoma.
AB  - OBJECTIVE: Studies have shown that angiogenesis is a critical factor for tumor
      growth and metastasis in a variety of human tumors. Although various methods have
      been tried to assess vessels in tumors, including microvessel density (MVD),
      assessment of tumor vessels by radiologic techniques is not well established. The
      aim of this study was to investigate the efficacy of contrast-enhanced
      ultrasonography (CEUS) in determining the tumor vascularity of hepatocellular
      carcinoma (HCC). METHODS: Contrast-enhanced ultrasonography was done in 50
      patients with HCC, which was shown histopathologically through subsequent hepatic
      resection. A contrast pulse sequencing technique and quantitative auto-tracking
      contrast quantification software were used to analyze the peak intensity (PI) of
      HCC. Immunohistochemistry was performed to evaluate the level of MVD in HCC. Then
      the relationship between PI and the level of MVD was analyzed. RESULTS: The mean
      PIs of HCC and peripheral tissue +/- SD were 135.19 +/- 28.16 and 72.91 +/- 19.22
      dB, respectively. The MVDs of HCC and peripheral tissue were 43.44 +/- 12.22 and
      17.14 +/- 9.18, respectively. The values of PI and MVD of HCC were significantly
      higher than those of peripheral tissue. A significant correlation was found
      between PI and MVD in HCC tissues (P < .05). CONCLUSIONS: The PI in CEUS could
      reflect the MVD in HCC. Therefore, quantification of CEUS seems to be helpful for
      assessment of tumor vascularity in HCC.

PMID- 17526608
TI  - Differential diagnosis of gallbladder diseases with contrast-enhanced harmonic
      gray scale ultrasonography.
AB  - OBJECTIVES: We evaluated the usefulness of contrast-enhanced harmonic gray scale
      ultrasonographic findings for differential diagnosis of gallbladder diseases.
      METHODS: We evaluated contrast-enhanced harmonic gray scale ultrasonographic
      images from 33 patients with 35 polypoid gallbladder disease lesions larger than
      10 mm in diameter, consisting of 12 biliary sludge lesions, 8 cholesterol polyps,
      1 inflammatory polyp, 2 adenomas, and 12 carcinomas. After a galactosepalmitic
      acid contrast agent was injected, lesions were scanned by contrast-enhanced
      harmonic gray scale ultrasonography in 2 phases: early vascular and late
      vascular. RESULTS: None of the biliary sludge lesions (n = 12) showed either
      tumor vessels or tumor enhancement. Lesions showing tumor vessels and tumor
      enhancement on contrast-enhanced harmonic gray scale ultrasonography were
      diagnosed as cholesterol polyp, inflammatory polyp, adenoma, or carcinoma. Three
      (38%) of the 8 cholesterol polyps showed dotted-type tumor vessels. Branched-type
      tumor vessels were observed in 5 (62%) of the 8 cholesterol polyps, the 1 (100%)
      inflammatory polyp, both (100%) adenomas, and 3 (25%) of the 12 carcinomas.
      Tortuous-type tumor vessels were observed in 9 (75%) of the 12 carcinomas.
      Lesions with tumor enhancement and tortuous-type tumor vessels on contrast
      enhanced harmonic gray scale ultrasonography were diagnosed as carcinomas, and
      the sensitivity, specificity, and accuracy of this diagnosis with the current
      modality were 75% (9/12), 100% (23/23), and 91% (32/35), respectively.
      CONCLUSIONS: Evaluation of tumor vessels on contrast-enhanced harmonic gray scale
      ultrasonography may be a useful modality for differentiating gallbladder
      carcinoma from other polypoid gallbladder disease lesions.

PMID- 17526609
TI  - Diagnosis of focal liver masses on ultrasonography: comparison of unenhanced and
      contrast-enhanced scans.
AB  - OBJECTIVE: The purpose of this study was to compare the diagnostic accuracy,
      confidence level, and recommended management of focal liver masses after contrast
      enhanced ultrasonography (CEUS) compared with unenhanced ultrasonography alone.
      METHODS: One hundred sixty-seven patients were referred for CEUS to characterize
      a focal liver mass. A 2-person blind read determined benignancy or malignancy,
      comparative diagnosis, and accuracy on both ultrasonography and CEUS. Results
      were compared with the final diagnoses. RESULTS: The 2 readers could not
      determine benignancy or malignancy in 77 (46.1%) and 46 (27.5%) of 167 unenhanced
      scans compared with 2 (1.2%) and 1 (0.6%) of 167 CEUS scans. The confidence level
      increased from 0 responses in the 2 highest grades (4 and 5) on the unenhanced
      scans to 135 (81.8%) and 132 (79.5%) of 167 at level 5 for CEUS. Regarding the
      diagnosis, the confidence level was lowest (grade 1) on the unenhanced scans in
      128 (82.1%) and 79 (65.3%) of 167 for the 2 readers and improved to the highest
      (grade 5) in 110 (65.9%) and 113 (68.1%) of 167. Regarding diagnostic accuracy,
      the unenhanced scans agreed with the correct diagnosis in 85 (50.9%) and 63
      (37.7%) of 167, and CEUS agreed with the correct diagnosis in 133 (79.6%) and 142
      (85%) of 167 for readers 1 and 2, respectively. Recommendations for further
      imaging decreased from 166 (99.4%) and 147 (88%) of 167 on the unenhanced scans
      to 30 (18%) and 5 (3%) of 167 on CEUS for readers 1 and 2. CONCLUSIONS: Contrast
      enhanced ultrasonography improves the accuracy and confidence of diagnosis of
      focal liver lesions and reduces recommendations for further investigations.

PMID- 17526610
TI  - Sonographic features of liver involvement by lymphoma.
AB  - OBJECTIVE: The liver is one of the most frequent extranodal locations of non
      Hodgkin lymphoma and Hodgkin disease. Nevertheless, lymphoma constitutes only 6%
      to 8% of focal lesions of the liver. Few studies have evaluated the sonographic
      patterns of lymphoma with liver involvement. The purpose of this study was to
      describe the sonographic features and to evaluate the accuracy of sonography for
      the diagnosis of lymphoma with liver infiltration. METHODS: The abdominal
      sonographic findings of 23 consecutive patients with histologically proven
      diagnosis of lymphoma with liver involvement were reviewed. RESULTS: The most
      prevalent sonographic features were hepatomegaly and splenomegaly. Abdominal
      lymphoadenopathies were identified in 34.8% of cases. Liver nodules were seen in
      half of patients, and the most frequent sonographic appearance was as multiple
      small focal lesions. Differences in sonographic patterns between high- and low
      grade non-Hodgkin lymphoma were not seen. None of the patients with Hodgkin
      disease had liver nodules. Concordance between sonography and computed tomography
      for the diagnosis of focal liver lesions was observed. CONCLUSIONS: Sonography
      may contribute to the diagnosis of liver infiltration by lymphoma. The presence
      of multiple focal liver lesions associated with splenomegaly and
      lymphoadenopathies should make us consider the diagnosis of lymphoma with liver
      involvement. Nevertheless, the low specificity of these findings requires
      histologic confirmation of lymphomatous infiltration of the liver.

PMID- 17526611
TI  - Ultrasound thyroid elastography using carotid artery pulsation: preliminary
      study.
AB  - OBJECTIVE: The purpose of this study was to evaluate the feasibility of
      ultrasound thyroid elastography using carotid artery pulsation as the compression
      source and its potential for differential diagnosis of thyroid nodules. METHODS:
      Baseband sonographic data were acquired for 16 thyroid nodules from 12 patients.
      The natural pulsation of the carotid artery was used as the compression source,
      and thyroid strain was estimated offline. For quantitative assessment of thyroid
      tissue stiffness, a new metric called the thyroid stiffness index (TSI) was
      computed as the ratio of strain near the carotid artery (high-strain region) to
      that of a stiff region (low-strain region) inside a thyroid nodule. The stiffness
      information from elastography was correlated with histopathologic findings.
      RESULTS: The TSI for papillary carcinoma (n = 9) was higher than the TSI for a
      benign nodular goiter (n = 6), indicating that papillary carcinoma is stiffer
      than a benign nodular goiter (P < .05). In 1 patient, we were able to distinguish
      a papillary carcinoma nodule and a benign nodular goiter located in the same
      thyroid lobe based on the stiffness information obtained from elastography. This
      suggests that elastography could be used for guiding fine-needle aspiration
      biopsy to a thyroid nodule with a high probability of cancer. CONCLUSIONS: The
      results from this preliminary study indicate the feasibility of the pulsation
      induced thyroid elastography. Ultrasound thyroid elastography using carotid
      artery pulsation appears to have the potential for noninvasively differentiating
      papillary carcinoma from benign nodular goiter. Future studies are needed to
      evaluate the efficacy of elastography in detecting thyroid cancer and guiding
      thyroid biopsies.

PMID- 17526612
TI  - Comparison of ultrasound elastography, mammography, and sonography in the
      diagnosis of solid breast lesions.
AB  - OBJECTIVE: The purpose of this study was to evaluate the value of ultrasound
      elastography (UE) in differentiating benign versus malignant lesions in the
      breast and compare it with conventional sonography and mammography. METHODS: From
      September 2004 to May 2005, 296 solid lesions from 232 consecutive patients were
      diagnosed as benign or malignant by mammography and sonography and further
      analyzed with UE. The diagnostic results were compared with histopathologic
      findings. The sensitivity, specificity, accuracy, positive and negative
      predictive values, and false-positive and -negative rates were calculated for
      each modality and the combination of UE and sonography. RESULTS: Of 296 lesions,
      87 were histologically malignant, and 209 were benign. Ultrasound elastography
      was the most specific (95.7%) and had the lowest false-positive rate (4.3%) of
      the 3 modalities. The accuracy (88.2%) and positive predictive value (87.1%) of
      UE were higher than those of sonography (72.6% and 52.5%, respectively). The
      sensitivity values, negative predictive values, and false negative rates of the 3
      modalities had no differences. A combination of UE and sonography had the best
      sensitivity (89.7%) and accuracy (93.9%) and the lowest false-negative rate
      (9.2%). The specificity (95.7%) and positive predictive value (89.7%) of the
      combination were better, and the false-positive rate (4.3%) of the combination
      was lower than those of mammography and sonography. CONCLUSIONS: In a clinical
      trial with Chinese women, UE was superior to sonography and equal or superior to
      mammography in differentiating benign and malignant lesions in the breast. A
      combination of UE and sonography had the best results in detecting cancer and
      potentially could reduce unnecessary biopsy. Ultrasound elastography is a
      promising technique for evaluating breast lesions.

PMID- 17526613
TI  - Sonographic features of breast carcinoma presenting as masses in BRCA gene
      mutation carriers.
AB  - OBJECTIVE: The purpose of this study was to review the sonographic features of
      breast cancer gene BRCA1- and BRCA2-associated breast carcinomas in comparison
      with "sporadic" breast carcinomas and benign breast masses. METHODS: Sonograms of
      233 breast masses, including 33 BRCA-associated malignant masses (BRCA1, 15;
      BRCA2, 18), 148 sporadic malignant masses, and 52 benign masses, were reviewed by
      consensus by 2 radiologists according to American College of Radiology Breast
      Imaging Reporting and Data System (BI-RADS) terminology. RESULTS: Most of the
      sporadic and BRCA1-and BRCA2-associated cancers displayed an irregular shape
      (91.2%, 93.3%, and 83.3%, respectively). BRCA1-associated cancers showed
      microlobulated margins in 53.3% versus 33.8% (sporadic) and 33.3% (BRCA2). A
      parallel orientation was most frequently encountered in BRCA1-associated lesions
      (46.7%) versus sporadic (33.8%) and BRCA2 (33.3%), whereas posterior acoustic
      shadowing was least frequently seen in BRCA1-associated lesions (13.3%) versus
      BRCA2 (16.7%) and sporadic (31.1%). Most (73.3%) of the BRCA1-associated lesions
      were classified as BI-RADS category 4, whereas most of the sporadic and BRCA2
      associated lesions were classified as BI-RADS category 5 (66.2% and 72.2%).
      CONCLUSIONS: Sonographic features of BRCA-associated and sporadic breast
      carcinomas do not differ substantially. BRCA1-associated breast carcinomas trend
      toward less malignant sonographic characteristics, but strict application of the
      BI-RADS categorizations demands that they be classified as category 4 or 5.

PMID- 17526614
TI  - The value of repeated evaluation after initial failed nuchal translucency
      measurement.
AB  - OBJECTIVE: The purpose of this study was to assess the value of reattempting the
      nuchal translucency (NT) measurement after an initial failure. METHODS: Women
      undergoing NT measurements by NT-certified sonographers within a combined
      screening program over an 18-month period were categorized as "desiring"
      screening (all women), "eligible" (live fetus with crown-rump length of 45-84
      mm), and "defaulters" (failed to keep a visit after a failed NT measurement
      attempt). If the NT measurement was unobtainable, patients with live fetuses and
      a crown-rump length of less than 84 mm were offered reexamination. RESULTS:
      Nuchal translucency measurement success rates at the initial visit for those
      desiring (n = 837) and eligible (n = 767) were 73.3% and 80.0%, respectively.
      Composite NT measurement success rates for up to 3 visits were significantly
      greater than for only 1 visit for those desiring screening (84.8%; P < .0001),
      eligible for screening (86.6%; P = .0004), and not defaulting on follow-up
      (97.0%; P < .0001). The screen-positive rates were similar for 1 and up to 3
      visits (10.4% and 11.0%). One additional (16.6%) aneuploidy was detected through
      a second visit. CONCLUSIONS: Reattempting NT measurements significantly increases
      the overall NT measurement success rate and detects additional aneuploidies at
      constant screen-positive and invasive prenatal diagnosis rates.

PMID- 17526615
TI  - Usefulness of ultrasonographic detection of talocrural effusion in ankle sprains.
AB  - OBJECTIVE: Ankle sprain severity is difficult to assess initially in the
      emergency department, yet it governs treatment decisions. Ultrasonography readily
      shows fluid present in the talocrural joint, which is difficult to assess by
      physical examination. The purpose of this study was to evaluate the prevalence of
      ultrasonographic talocrural joint effusion in moderate and severe ankle sprains
      and to determine the cause of effusions by magnetic resonance imaging (MRI).
      METHODS: Consecutive patients 18 to 55 years of age with moderate and severe
      ankle sprains within the previous 48 hours were included if they had no history
      of abnormalities in the same ankle within the last 12 months. When
      ultrasonography with the ankle in the neutral position showed talocrural
      effusion, MRI was performed within 8 days. RESULTS: Of the 110 patients (83 men
      and 27 women; mean age, 24.2 years), 40 (36.4%; 95% confidence interval, 27.6%
      46.1%) had joint effusion on ultrasonography and MRI. In 39 of these 40 patients,
      MRI visualized damage to the anterior talofibular ligament (positive predictive
      value, 97.5%; 95% confidence interval, 85.3%-99.9%), accompanied in 5 (12.8%)
      cases by damage to the calcaneofibular ligament. In 14 (35%) cases, MRI showed
      cartilage damage or bony contusion. CONCLUSIONS: Talocrural effusion on
      ultrasonography may identify patients with severe ankle sprains. Magnetic
      resonance imaging should be performed in patients with talocrural effusion.
      Further work is needed to evaluate the usefulness of MRI in acute ankle sprains
      without talocrural effusion.

PMID- 17526616
TI  - Quantitative analysis of tumor vascularity in benign and malignant solid thyroid
      nodules.
AB  - OBJECTIVE: The purpose of our study was to analyze the accuracy of quantitative
      analysis of tumor vascularity on power Doppler sonograms in differentiating
      malignant and benign solid thyroid nodules using tumor histologic evaluation as
      the reference standard. Methods. Eighty-six solid thyroid tumors (46 malignant
      and 40 benign) in 56 consecutive patients (mean age +/- SD, 53.1 +/- 11.6 years;
      12 male and 44 female) referred for the surgical treatment were included in our
      study. Visual and qualitative analysis of patterns of nodule vascularity was
      performed for all tumors. Quantification of the power Doppler sonograms was
      performed with normalized and weighted vascular indices (VIs). The accuracy of
      sonographic criteria for thyroid cancer was evaluated with univariate analysis.
      Results. Among benign thyroid tumors, there was a statistically significant
      increase in the levels of intranodular vascularization with an increase in tumor
      size (P < .001). In all tumors, increased intranodular vascularization showed
      65.2% sensitivity, 52.5% specificity, and 58.9% overall accuracy in
      differentiation between benign and malignant thyroid lesions. In tumors smaller
      than 2 cm, it had 65.5% sensitivity, 85.7% specificity, and 72.1% overall
      accuracy. Quantitative analysis of tumor vascularity significantly overperformed
      visual analysis of power Doppler patterns (P < .05). Among thyroid lesions with
      diameters of less than 2 cm, a normalized VI of greater than 0.14 had 72.4%
      sensitivity, 100% specificity, and 86.2% overall accuracy. A weighted VI of
      greater than 0.24 showed compatible results, with 69.0% sensitivity, 100%
      specificity, and 84.5% overall accuracy. CONCLUSIONS: Our study indicates that in
      small thyroid nodules, quantitative analysis of tumor vascularity has benefits
      over visual inspection and can be useful in differentiation between benign and
      malignant thyroid tumors.

PMID- 17526617
TI  - Recurrent hyperparathyroidism secondary to parathyromatosis: clinical and imaging
      findings.
AB  - OBJECTIVE: Parathyromatosis, a condition in which hyperfunctioning parathyroid
      tissue is distributed throughout the neck, is a rare but challenging cause of
      recurrent hyperparathyroidism after parathyroidectomy. The purpose of this series
      is to describe the imaging appearance of parathyromatosis and the potential
      utility of sonographic localization before resection. METHODS: Imaging is
      routinely performed in an attempt to identify autonomous residual parathyroid
      glands in patients with recurrent hyperparathyroidism after parathyroidectomy.
      The sonographic and technetium Tc 99m sestamibi studies and the clinical records
      of 2 patients with recurrent hyperparathyroidism secondary to parathyromatosis
      were reviewed. RESULTS: Color Doppler sonography easily identified scattered deep
      and superficial hypoechoic, hypervascular cervical nodules that did not conform
      to typical anatomic locations of parathyroid glands; the nodules corresponded to
      areas of delayed tracer uptake at Tc 99m sestamibi single-photon emission
      computed tomography. Intraoperative mapping of nodules aided the successful
      resection of widespread parathyromatosis in 1 patient. CONCLUSIONS: Although the
      sonographic appearance of parathyromatosis may mimic disseminated cervical
      malignancy, a confident diagnosis of this rare entity may be made in the
      appropriate clinical setting. Sonography may also aid in directing the resection
      of disseminated parathyroid tissue in selected patients.

PMID- 17526618
TI  - Contrast-enhanced ultrasonographic features of a solid-cystic papillary tumor of
      the pancreas.

PMID- 17526619
TI  - Olecranon bursitis communicating with an olecranon cyst in rheumatoid arthritis.

PMID- 17526620
TI  - Sonographic evaluation of the endometrium in patients with a history or an
      appearance of polycystic ovarian syndrome.

PMID- 17526621
TI  - Effect of plyometric training on sand versus grass on muscle soreness and jumping
      and sprinting ability in soccer players.
AB  - OBJECTIVE: The lower impact on the musculoskeletal system induced by plyometric
      exercise on sand compared to a firm surface might be useful to reduce the stress
      of intensified training periods or during rehabilitation from injury. The aim of
      this study was to compare the effects of plyometric training on sand versus a
      grass surface on muscle soreness, vertical jump height and sprinting ability.
      DESIGN: Parallel two-group, randomised, longitudinal (pretest-post-test) study.
      METHODS: After random allocation, 18 soccer players completed 4 weeks of
      plyometric training on grass (grass group) and 19 players on sand (sand group).
      Before and after plyometric training, 10 m and 20 m sprint time, squat jump (SJ),
      countermovement jump (CMJ), and eccentric utilization ratio (CMJ/SJ) were
      determined. Muscle soreness was measured using a Likert scale. RESULTS: No
      training surface x time interactions were found for sprint time (p>0.87), whereas
      a trend was found for SJ (p = 0.08), with both groups showing similar
      improvements (p<0.001). On the other hand, the grass group improved their CMJ (p
      = 0.033) and CMJ/SJ (p = 0.005) significantly (p<0.001) more than players in the
      sand group. In contrast, players in the sand group experienced less muscle
      soreness than those in the grass group (p<0.001). CONCLUSIONS: Plyometric
      training on sand improved both jumping and sprinting ability and induced less
      muscle soreness. A grass surface seems to be superior in enhancing CMJ
      performance while the sand surface showed a greater improvement in SJ. Therefore,
      plyometric training on different surfaces may be associated with different
      training-induced effects on some neuromuscular factors related to the efficiency
      of the stretch-shortening cycle.

PMID- 17526622
TI  - Reference intervals for serum creatine kinase in athletes.
AB  - BACKGROUND: The serum concentration of creatine kinase (CK) is used widely as an
      index of skeletal muscle fibre damage in sport and exercise. Since athletes have
      higher CK values than non-athletes, comparing the values of athletes to the
      normal values established in non-athletes is pointless. The purpose of this study
      was to introduce reference intervals for CK in athletes. METHOD: CK was assayed
      in serum samples from 483 male athletes and 245 female athletes, aged 7-44.
      Samples had been obtained throughout the training and competition period. For
      comparison, CK was also assayed in a smaller number of non-athletes. Reference
      intervals (2.5th to 97.5th percentile) were calculated by the non-parametric
      method. RESULTS: The reference intervals were 82-1083 U/L (37 degrees C) in male
      and 47-513 U/L in female athletes. The upper reference limits were twice the
      limits reported for moderately active non-athletes in the literature or
      calculated in the non-athletes in this study. The upper limits were up to six
      times higher than the limits reported for inactive individuals in the literature.
      When reference intervals were calculated specifically in male football (soccer)
      players and swimmers, a threefold difference in the upper reference limit was
      found (1492 vs 523 U/L, respectively), probably resulting from the different
      training and competition demands of the two sports. CONCLUSION: Sport training
      and competition have profound effects on the reference intervals for serum CK.
      Introducing sport-specific reference intervals may help to avoid
      misinterpretation of high values and to optimise training.

PMID- 17526623
TI  - Heart rate variability modifications following exercise training in type 2
      diabetic patients with definite cardiac autonomic neuropathy.
AB  - OBJECTIVES: Cardiac autonomic neuropathy (CAN) as a result of diabetic autonomic
      neuropathy is positively related to a poor prognosis in diabetic patients. The
      measurement of heart rate variability (HRV) is a remarkable index of cardiac
      autonomic dysfunction. The aim of this study was to examine the effects of long
      term exercise training on HRV in type 2 diabetic patients with definite CAN.
      METHODS: Seventeen type 2 diabetic patients with definite CAN (group A: 56.2
      years (SD 5.8)) and 15 without CAN (group B: 55.8 years (SD 5.6)) participated in
      the study. All patients followed an aerobic exercise training programme three
      times a week for 6 months; the intensity of the session was 70% to 85% of heart
      rate reserve. At the beginning and end of the study all subjects underwent graded
      maximal exercise testing with spiroergometry for the evaluation of their aerobic
      capacity (VO(2)peak). Moreover, time and frequency domain indices of HRV were
      obtained from 24 h ambulatory continuous ECG Holter recordings. RESULTS: At
      baseline, all measurements of HRV indices were significantly reduced in group A
      compared with group B (p<0.05). Moreover, group A reached a significantly lower
      VO(2)peak by 14.8% compared with group B (p<0.05). Following the exercise
      training programme, the SD of all normal-to-normal RR intervals in the entire
      recording (SDNN) was increased by 18.8% (p<0.05) and 13.8% (p<0.05), the square
      root of the average of sum of squares of difference between adjacent filtered RR
      intervals (rMSSd) was increased by 35% (p<0.05) and 15.2% (p<0.05), and the
      percentage of differences between adjacent filtered RR intervals which was
      greater than 50 ms for the entire analysis (pNN50) was increased by 400% (p<0.05)
      and 67.9% (p<0.05) in groups A and B, respectively. Regarding the frequency
      domain indices, only the high frequency power (HF) was found to be significantly
      increased in group A. At the end of the exercise training programme, SDNN, rMSSd
      and low frequency power (LF) were significantly lower (24.3% (p<0.05), 20.3%
      (p<0.05) and 40% (p<0.05), respectively) in group A compared with group B. Also,
      VO(2)peak increased by 17.8% (p<0.05) in group A and by 11% (p<0.05) in group B.
      Furthermore, the exercise training programme had significant effects on blood
      lipid and glucose levels and glycosylated haemoglobin (HbA(1c)) in both groups.
      CONCLUSIONS: The results indicate that 6-month aerobic exercise training improves
      the cardiac autonomic nervous system function in type 2 diabetic patients.
      However, more favourable effects are found in type 2 diabetic patients with
      definite CAN.

PMID- 17526624
TI  - Rule change incidence on physiological characteristics of elite basketball
      players: a 10-year-period investigation.
AB  - OBJECTIVE: To evaluate, by examining data collected on professional basketball
      players during a 10-year period, the differences in aerobic capacity in function
      of the playing position and the impact on these parameters of the change in time
      regulation of 2000, which shortened the time allowed to attempt a field goal by 6
      s and divided the duration of play in four quarters. METHODS: Twice a year
      between 1994 and 2004, professional basketball players (n = 68) were studied for
      anthropometric characteristics and were submitted to an incremental exercise test
      on a cycle ergometer. Statistical analyses were carried out to determine the
      interaction between the playing position and the effect of the change in time
      regulation on the physiological characteristics of the players. RESULTS:
      Anthropometric measurements were different in function of the playing position,
      the centres being taller and heavier than the forwards and the guards. Guards
      exhibited the highest Vo(2)max (54.0 (SE 1.6) ml/min/kg) and were the most
      affected by the change in time regulation of 2000 with a 19.5% increase.
      Significant main effects of "before" versus "after" rule changes were found for
      maximal and submaximal O(2) consumption, which were increased by 12.8% at
      ventilatory threshold, 7.3% at respiratory compensation point and 7.8% at
      Vo(2)max. CONCLUSION: While anthropometric characteristics remained constant
      during the last decade, the change in rule of 2000 may have contributed in
      modifying the physiological profile of basketball players, by generally
      increasing their level of fitness.

PMID- 17526626
TI  - Smoking kills (alcoholics)! shouldn't we do something about it?
AB  - In general, 'drinkers smoke', and a high proportion of the alcohol-dependent
      population is also nicotine-dependent. Statistically, the majority of alcoholics
      will die of smoking-related, rather than alcohol-related, disease. This co
      dependent sub-population may have higher levels of nicotine dependence, and find
      smoking cessation more difficult. Major reasons are that concurrent alcohol use,
      and/or prior alcohol exposure, may change the reinforcing effects of nicotine,
      and that each drug becomes a pharmacological cue for the expectation of the
      other. If so, then smokers whose nicotine dependence is impacted by alcohol,
      represent a large and distinct sub-population in which both the therapeutic and
      molecular targets for smoking cessation are altered. This, in turn, has
      implications for the validity of animal models of nicotine reinforcement, and for
      the development of novel smoking cessation medications. It is no longer possible
      to ignore the fact that the two most prevalent and damaging addictive drugs in
      our society are very commonly used by the same individuals. Without a better
      understanding of the psychological and pharmacological interactions between
      alcohol and nicotine that impact dependence, we cannot hope to provide
      appropriate medications for this large and problematic patient group. Our
      intention in this opinion overview is to use the current literature to provide a
      framework for future studies into the impact of alcohol use on the reinforcing
      effects of nicotine.

PMID- 17526627
TI  - The neurobiological and neurocognitive consequences of chronic cigarette smoking
      in alcohol use disorders.
AB  - A vast body of research attests to the adverse effects of chronic smoking on
      cardiac, pulmonary, and vascular function as well as the increased risk for
      various forms of cancer. However, comparatively little is known about the effects
      of chronic smoking on human brain function. Although smoking rates have decreased
      in the developed world, they remain high in individuals with alcohol use
      disorders. Despite the high prevalence of comorbid chronic smoking in alcohol use
      disorders, very few studies have addressed the potential neurobiological or
      neurocognitive effects of chronic smoking in alcohol use disorders. Here, we
      briefly review the existing literature on the neurobiological and neurocognitive
      consequences of chronic cigarette smoking and summarize our neuroimaging and
      neurocognitive studies on the effects of comorbid chronic excessive alcohol
      consumption and cigarette smoking in treatment-seeking and treatment-naive
      populations. Our research suggests comorbid chronic cigarette smoking modulates
      magnetic resonance-detectable brain injury and neurocognition in alcohol use
      disorders and that neurobiological recovery in our abstinent alcoholics is
      adversely affected by chronic smoking. Consideration of the potential separate
      effects and interactions of chronic smoking and alcohol consumption may foster a
      better understanding of specific mechanisms and neurocognitive consequences of
      brain injury in alcoholism and of brain recovery during sustained abstinence from
      alcohol. The material presented also contributes to ongoing discussions about
      treatment strategies for comorbid alcoholism and cigarette smoking and will
      hopefully stimulate further research into the neurobiological and neurocognitive
      consequences of chronic smoking in alcoholism and other substance use disorders.

PMID- 17526628
TI  - Predicting alcohol misusers' readiness and ability to quit smoking: a critical
      review.
AB  - AIMS: The prevalence of smoking among individuals with alcohol use disorders
      (AUD) and other substance use disorders is alarmingly high, and long-term success
      rates of smoking cessation interventions in this group are low. One way to
      improve treatment efficacy for this population is through a more comprehensive
      understanding of individual- and treatment-level variables that affect the
      motivation to quit as well as the outcomes of smoking cessation attempts. In this
      paper, we review the relevant research on factors that may influence readiness to
      quit and the efficacy of smoking cessation interventions in this population and
      highlight gaps in the knowledge base that require further investigation. METHODS:
      We conducted a review of the literature on smoking among adults with AUD in order
      to examine predictors of motivation to quit smoking and outcome of cessation
      attempts. RESULTS: No consistent predictors of motivation for smoking cessation
      were identified. Although the results were not unanimous, a greater length of
      abstinence from alcohol and other substances predicted smoking cessation success.
      CONCLUSIONS: Empirical work identifying factors associated with the motivation
      and ability to quit smoking among individuals with AUD is in its early stages.
      Mixed results and a dearth of research in this area prohibit strong conclusions
      from being made. Future researchers are encouraged to consider alternative
      methods of conceptualizing and measuring motivations to quit in this group and to
      routinely include analyses that examine predictors of outcome in intervention
      studies.

PMID- 17526630
TI  - Nicotine increases ethanol preference but decreases locomotor activity during the
      initial stages of chronic ethanol withdrawal.
AB  - AIM: The ability of nicotine to modify withdrawal symptoms in rats chronically
      treated with alcohol, with respect to locomotor activity and ethanol or nicotine
      preference, has been evaluated in these studies. METHODS AND RESULTS: Preliminary
      studies showed that locomotor activity increased 8-9 h after withdrawal from
      chronic nicotine intoxication, which was dose specific; it occurred in rats
      administered 0.15 mg/kg or 0.6 mg/kg but not the 0.3 mg/kg nicotine dose.
      Administration of nicotine, either acutely (0.3 mg/kg) during ethanol withdrawal,
      or chronically (0.15, 0.3 or 0.6 mg/kg) during the chronic alcohol treatment
      procedure, diminished locomotor activity, which increases significantly,
      approximately 6-7 h after withdrawal, in rats chronically treated with alcohol.
      Rats which were chronically treated with alcohol alone or in combination with
      nicotine, 0.3 mg/kg, showed an increase in ethanol intake when the free choice
      was performed between ethanol 10% and tap water; on the contrary, when the free
      choice was performed between ethanol 10% versus nicotine, 0.3 mg/kg, results
      showed a decrease in ethanol preference and a concomitant increase in nicotine
      preference. CONCLUSION: These studies clearly identified the modulatory effects
      of nicotine, at specific doses, on both motility and preference in rat
      chronically co-administered nicotine and ethanol.

PMID- 17526629
TI  - Alcohol history and smoking cessation in nicotine replacement therapy, bupropion
      sustained release and varenicline trials: a review.
AB  - AIMS: We conducted a review of published reports of smoking cessation
      pharmacotherapy trials in order to address the following: (i) the
      generalizability of findings to smokers with a history of alcohol problems; (ii)
      the extent to which alcohol use affects smoking cessation overall and the
      efficacy of pharmacotherapy specifically and (iii) the effect of smoking
      cessation on alcohol use. METHODS: We located published reports of nicotine
      replacement therapy (NRT), bupropion sustained release (SR) and varenicline
      clinical trials using an approach based on prior Cochrane reviews. The reports
      were searched for alcohol-related inclusion/exclusion criteria and for findings
      related to alcohol. RESULTS: The present review included 212 published reports
      from 149 trials. Alcohol-related exclusion criteria appeared frequently (41.6% of
      trials)--45/125 NRT trials (36%), 15/22 bupropion SR trials (68.2%) and 3/3
      varenicline trials--and most commonly involved exclusion of participants with
      either current or recent alcohol problems. Most studies failed to provide any
      baseline alcohol-related characteristics. Eleven trials reported on the
      relationship between alcohol history and likelihood of smoking cessation. In the
      majority of these studies, smokers with a past history of alcohol problems were
      not at a disadvantage, although contrary findings exist. Only two studies
      examined the potential influence of smoking cessation on alcohol use.
      CONCLUSIONS: Smokers with alcohol problems, particularly those with current or
      recent problems, are underrepresented in studies of approved pharmacotherapy for
      smoking cessation. Future trials should assess alcohol use at baseline and during
      treatment and examine reciprocal influences between alcohol consumption and
      smoking cessation.

PMID- 17526631
TI  - Concurrent alcohol and tobacco use during early adolescence characterizes a group
      at risk.
AB  - AIMS: To investigate whether concurrent alcohol and tobacco use during early
      adolescence characterizes a subgroup that differs from users of one substance
      only regarding several risk factors for later substance use problems. METHODS:
      Participants were from a prospective longitudinal cohort study of 384 children at
      risk for later psychopathology, with the majority being born with obstetric
      complications and psychosocial adversities. Assessments of adolescent drug
      consumption and related intrapersonal characteristics were obtained at age 15.
      RESULTS: Compared to consumers of alcohol only, 15-year-olds drinking and smoking
      during the same time period (past 4 weeks) had significantly higher levels of
      consumption and more excessive use of alcohol, started drinking at an earlier
      age, had higher scores on the Fagerstrom Test for Nicotine Dependence, and more
      cannabis use. This group could be distinguished from users of alcohol only by
      higher novelty seeking and more positive alcohol effect expectancies. Compared to
      consumers of tobacco only, concurrent users reported higher nicotine dependence
      and more cannabis use. No significant differences were observed regarding
      frequency and age at initiation of tobacco use, tobacco-related sensitivity, self
      efficacy and instrumentality as well as novelty seeking. CONCLUSIONS: Concurrent
      alcohol and tobacco use during early adolescence is associated with
      characteristics that are well known as risk factors for later alcohol use
      problems and dependence and that should be targeted by prevention programs.

PMID- 17526633
TI  - Timevarying predictors of smoking cessation among individuals in treatment for
      alcohol abuse and dependence: findings from Project MATCH.
AB  - AIMS: Individuals in treatment for alcohol use disorders are more likely to die
      from cigarette use than from alcohol consumption. Advanced statistical
      methodologies that increase study power and clinical relevance have been
      advocated to examine the timevarying nature of substance use relapse and
      abstinence, including drinking and smoking. The purpose of this investigation was
      to examine timevarying factors that are associated with smoking cessation among
      smokers in the general population, including alcohol use, self-efficacy, and
      depression, to determine if they were also related to smoking cessation during
      and after treatment for alcohol use disorders. METHODS: Data were garnered from
      Project MATCH, a longitudinal prospective study of the efficacy of three
      behavioural treatments for alcohol use disorders. Timevarying covariate analyses
      were conducted to examine future smoking cessation. RESULTS: Results showed that
      greater self-efficacy regarding resisting temptations to drink and lower levels
      of depression were independently associated with increased likelihood of stopping
      smoking. In contrast, drinks per drinking day and confidence regarding not
      drinking did not demonstrate such associations. CONCLUSIONS: Clinical
      implications of these findings suggest that interventions to help alcoholics in
      recovery avoid temptations to drink, as well as decrease depression, may be
      warranted. By using advanced statistical techniques, these results can help
      clinicians and organizations working with smokers in treatment for alcohol use
      disorders to make informed decisions regarding how best to use limited resources.

PMID- 17526632
TI  - Is cigarette smoking related to alcohol use during the 8 years following
      treatment for adolescent alcohol and other drug abuse?
AB  - AIMS: The present study examined the relationship between cigarette smoking and
      alcohol use outcomes over an 8-year period following treatment for adolescent
      alcohol and other drug (AOD) use disorders. METHODS: The present study was based
      on a sample of 166 adolescents recruited during inpatient AOD abuse treatment.
      Included in this study were 123 (74% of the full sample) participants, of whom
      41% were female, 81% identified themselves as White and who averaged 15.9 years
      of age (SD = 1.3) when entering treatment. Data for the present study were drawn
      from interviews conducted at the time of treatment and 2-, 4-, 6- and 8-years
      post-treatment. RESULTS: Twenty six percent of participants had quit smoking for
      > 1 year at the 8-year assessment, while 44% reported persistent smoking over
      time. Overall smoking rates decreased significantly over time. Subjects
      associated with the highest alcohol involvement trajectory reported significantly
      greater likelihood of persistent smoking as well as higher current smoking and
      cigarette consumption across time points. CONCLUSIONS: The significant declines
      observed in smoking from adolescence into young adulthood were contrary to
      expectations, indicating that this behaviour may be less stable than previously
      thought among adolescent AOD abusers. Smoking involvement over time was greater
      within the highest alcohol use trajectory, consistent with previous evidence for
      a positive relationship between these behaviours. However, when compared with the
      general population smoking rates remained very high regardless of alcohol
      involvement. Thus, individuals treated for AOD abuse as adolescents remained at
      elevated risk for tobacco related disease regardless of post-treatment AOD use
      outcomes.

PMID- 17526634
TI  - Results from two pharmacotherapy trials show alcoholic smokers were more severely
      alcohol dependent but less prone to relapse than alcoholic non-smokers.
AB  - AIMS: To assess the role of smoking on treatment outcome in quitting alcoholics
      on the background of the priming or coping hypothesis (Rohsenow et al., 1997).
      METHODS: Data sets of placebo treated patients of the German phase III trial of
      naltrexone (Gastpar et al., 2002) and of acamprosate treated patients of a German
      phase IV trial Soyka et al., 2002) were reanalyzed. Differences between smoking
      and non-smoking alcoholics were evaluated using chi(2)-, t- or ANOVA-tests,
      relapse rates using survival techniques with Cox regression. RESULTS: Smoking
      alcoholics differed significantly from non-smoking alcoholics regarding
      sociodemographic variables (e.g. more males, more often living alone) and
      severity indicators of alcoholism (e.g. quantity, onset, related problems). In
      the naltrexone study time to first relapse was significantly longer for smoking
      alcoholics compared to non-smoking alcoholics (hazard ratio = 2.26; P = 0.036).
      The same effect was seen in the acamprosate study (hazard ratio = 1.34; P =
      0.015); estimated abstinence-rates after 24 weeks were 38% for smoking alcoholics
      compared to 28% for non-smoking alcoholics (P < 0.015). CONCLUSIONS: Smoking was
      significantly associated with better outcome in recovering alcoholics included in
      two pharmacotherapy trials. Although the underlying mechanisms remain unclear our
      findings are in favour of the coping hypothesis. The results challenge the
      validity of the dependence syndrome.

PMID- 17526635
TI  - Tobacco use is associated with more severe alcohol dependence, as assessed by the
      number of DSM-IV criteria, in Swedish male type 1 alcoholics.
AB  - BACKGROUND: A high smoking prevalence has been reported in treatment-seeking
      alcohol-dependent individuals. It has also been suggested that alcohol-dependent
      individuals who smoke may have a more severe course and greater severity of their
      alcoholism. METHODS: This study evaluated the impact of tobacco use in 108
      Swedish male type 1 alcohol-dependent individuals, recruited by advertisement in
      a local daily newspaper. They were sub-grouped into smokers (N = 50), snuffers (N
      = 12) and tobacco nonusers (N = 46). The number of criteria for the diagnosis of
      alcohol dependence was used to assess the severity of alcohol dependence.
      RESULTS: The smokers were significantly younger compared to the tobacco non-using
      group, and also younger at their onset of excessive alcohol consumption. Both
      smokers and snuffers fulfilled significantly more DSM-IV criteria for alcohol
      dependence than tobacco nonusers. Furthermore, significantly higher proportions
      of smokers and snuffers fulfilled the criteria no 2 (experiencing withdrawal
      syndrome) and no 7 (continuing to use alcohol despite problems). CONCLUSIONS:
      These findings indicate that not only smoking, but also snuffing, is associated
      with greater severity of alcohol dependence, as reflected by the greater number
      of DSM-IV criteria.

PMID- 17526636
TI  - Association between smoking and alcohol use in the general population: stable and
      unstable odds ratios across two years in two different countries.
AB  - AIMS: The main objective of this article was to compare alcohol and tobacco
      consumption in the US and the Basque Country (the North of Spain) with particular
      attention to the association between alcohol and tobacco use. The consistency of
      findings was considered by analyzing data from two different years. These
      comparisons may provide a rational basis for exploring the associations between
      alcohol and cigarette use that are influenced by changes in use prevalences.
      METHODS: Two epidemiological samples from the US, obtained in 1992 and 1996, and
      two from the Basque Country, obtained in the same years, were used. Sampling
      methodologies were similar. Questionnaires were self-administrated with the help
      of interviewers, and were used to define ever smokers, ex-smokers, current
      smokers, heavy smokers, ever drinkers, ex-drinkers, current drinkers and weekly
      drinkers. The associations between smoking and alcohol drinking were explored
      through logistic regressions. RESULTS: The associations between current smoking
      and current drinking in the general population, and between ever smoking and
      weekly drinking among current drinkers appear very stable. In 1992 and 1996, US
      subjects who decided to try alcohol tended to try smoking and vice versa. In US
      Caucasians (particularly in 1996), heavy smoking was strongly associated with
      ever drinking among current smokers. In the Basque Country in 1992, there was a
      significant association between smoking cessation and drinking cessation among
      ever drinkers who also were ever smokers. CONCLUSIONS: Our analyses suggest that
      some associations between alcohol drinking and smoking behaviours are likely to
      be detected in Western countries where alcohol and nicotine are legal and easily
      available. On the other hand, other associations may be detected only in certain
      social contexts. These social contexts make the associations in subpopulations
      who are vulnerable to addiction, influence the results in the general population.
      In social contexts that exert considerable social pressure to quit smoking, such
      as in US Caucasians (particularly in 1996), heavy smoking was strongly associated
      with ever drinking among current smokers. When a social environment strongly
      discourages smoking and alcohol initiation (as in the US in 1992 and 1996),
      subjects who decide to try alcohol tend to try smoking and vice versa. The lack
      of social stigmatization of smoking and drinking in the Basque Country in 1992
      may help to explain the significant association between smoking cessation and
      drinking cessation among ever drinkers who also were ever smokers.

PMID- 17526637
TI  - D2 dopamine receptor gene haplotypes and their influence on alcohol and tobacco
      consumption magnitude in alcohol-dependent individuals.
AB  - INTRODUCTION: Alcohol dependence and habitual smoking frequently co-occur and
      possibly mutually influence each other. Both have been related to alterations of
      dopaminergic neurotransmission. The aim of this analysis of the Munich Gene Data
      Bank for Alcoholism(MGBA) was to re-evaluate the potential relation between D2
      receptor and dopamine transporter gene haplotypes and quantity-related phenotypes
      of alcohol consumption (average daily alcohol intake before admission for
      treatment) and smoking (average units smoked per day). METHODS: A total of 333
      inpatients (265 males) were enrolled in the study, all of who met the ICD10
      diagnosis of alcohol dependence. Mild and strong quantity drinkers and smokers
      were separated into groups by median split. A number of genetic markers were
      chosen across D2 dopamine receptor gene (-141 Ins/Del, Taq1B, Taq1D, Ser311Cys;
      rs1079594 (intron 7); Taq1A) and dopamine transporter (40bp variable number of
      tandem repeat; rs2617605 (intron 2); rs37022 (intron 7); rs40184 (intron 14)).
      Genotyping was performed using PCR. RESULTS: Strong drinkers reported
      significantly higher amounts of smoking and vice versa. While no association was
      detected for dopamine transporter genetic variants, a number of D2 receptor gene
      single nucleotide polymorphisms were related to both smoking- and drinking
      related behaviours. Subsequent analysis of D2 receptor gene haplotypes revealed
      that two common haplotypes had a significant association with quantitative
      phenotypes of regular drinking (Ins-C-G-C-A1) and smoking (Ins-T-G-A-A2).
      DISCUSSION: The finding of an association between common D2 dopamine receptor
      gene haplotypes with the quantity of drinking and smoking corroborates with
      results from previous studies suggesting a relationship between the dopamine
      system and alcohol and substance use disorders. Furthermore, it makes D2 dopamine
      receptor a candidate gene significantly influencing both alcohol and nicotine
      dependence.

PMID- 17526638
TI  - Different effects of smoking or use of smokeless tobacco on platelet MAO-B
      activity in type 1 alcohol-dependent subjects.
AB  - BACKGROUND: Low platelet monoamine oxidase (MAO)-B activity has been proposed as
      a marker for alcohol-dependence. Findings are, however, contradictory and the
      influence of confounding factors have been thoroughly investigated. Thus, it is
      now well established that cigarette smoking reduces platelet MAO-activity.
      However, not much is known about the influence of smokeless tobacco, i.e. snuff
      or chewing tobacco, on platelet MAO-B activity. The aim of the present study was
      to compare platelet MAO-B activity in type 1 alcohol-dependent subjects with
      concomitant use of smokeless tobacco (i.e. snuff users), use of smoking tobacco
      (i.e. cigarette smokers), and in those without any tobacco use. METHODS: Platelet
      MAO-B activity was examined in three groups of alcohol-dependent subjects: snuff
      users (n = 14), cigarette smokers (n = 33), and non-tobacco users (N = 46).
      RESULTS: In the alcohol-dependent subjects concomitant cigarette smokers, but not
      snuff users, were found to have significantly lower platelet MAO-B activity as
      compared to non-tobacco users (platelet MAO-B activity 4.0 +/- 1.5, 5.1 +/- 1.5
      and 5.0 +/- 1.9 microkat/kg protein, respectively). CONCLUSIONS: The findings in
      the present study suggests that in the alcohol-dependent subjects the concomitant
      use of smokeless tobacco, i.e. snuffing, does not have an inhibitory effect on
      platelet MAO-B activity. This may have implications for future research. Thus,
      alcohol-dependent subjects with concomitant tobacco use should be grouped
      separately according to the form of the tobacco used, i.e. smoking or smokeless
      tobacco.

PMID- 17526639
TI  - Health in our hands, but not in our heads: understanding hygiene motivation in
      Ghana.
AB  - Each year more than 2 million children die from diarrhoeal diseases; the same
      number again die from acute respiratory infections. The simple hygiene behaviour
      of washing hands with soap represents an effective way of preventing the
      transmission of many of these infections. However, rates of handwashing across
      the globe are low, presenting a challenge for health promotion programmes.
      Behaviour change is not easy, and past efforts based upon health education have
      met with limited success. New approaches are needed. We propose that much can be
      learnt from the world of consumer marketing. Rather than base communications
      programmes for behaviour change on increasing knowledge, marketers aim to respond
      to the inner desires and motivations of their target audiences. This study used
      consumer research to investigate the factors motivating handwashing with soap in
      order to inform a national communications campaign for Ghana. It revealed that
      the strongest motivators for handwashing with soap were related to nurturance,
      social acceptance and disgust of faeces and latrines, especially their smell.
      Protection from disease is mentioned as a driving force, but was not a key
      motivator of handwashing behaviour. The ways in which these findings have been
      translated into a handwash promotion campaign are discussed.

PMID- 17526640
TI  - Improving access to hospital care for the poor: comparative analysis of four
      health equity funds in Cambodia.
AB  - There is a large body of evidence that user fees in the health sector create
      exclusion. Health equity funds attempt to improve access to health care services
      for the poorest by paying the provider on their behalf. This paper reviews four
      hospital-based health equity funds in Cambodia and draws lessons for future
      operations. It investigates the practical questions of 'who should do what and
      how'. It presents, in a comparative framework, similarities and differences in
      objectives, the actors involved, design aspects and functional modalities between
      the health equity funds. The results of this review are presented along the lines
      of identification, hospitalization rates and relative costs. The four schemes had
      a positive impact on the volume of utilization of hospital services by the
      poorest patients. They now account for 7 to 52% of total hospital use. The
      utilization of hospitals by paying patients has remained constant in the same
      period. The comparative review shows that a range of operational arrangements may
      be adopted to achieve the health equity fund objectives. Our study identifies
      essential design aspects, and leaves different options open for others.

PMID- 17526641
TI  - Impact of packaged interventions on neonatal health: a review of the evidence.
AB  - A disproportionate burden of infant and under-five childhood mortality occurs
      during the neonatal period, usually within a few days of birth and against a
      backdrop of socio-economic deprivation in developing countries. To guide
      programmes aimed at averting these 4 million annual deaths, recent reviews have
      evaluated the efficacy and cost-effectiveness of individual interventions during
      the antenatal, intrapartum and postnatal periods in reducing neonatal mortality,
      and packages of interventions have been proposed for wide-scale implementation.
      However, no systematic review of the empirical data on packages of interventions,
      including consideration of community-based intervention packages, has yet been
      performed. To address this gap, we reviewed peer-reviewed journals and grey
      literature to evaluate the content, impact, efficacy (implementation under ideal
      circumstances), effectiveness (implementation within health systems), type of
      provider, and cost of packages of interventions reporting neonatal health
      outcomes. Studies employing more than one biologically plausible neonatal health
      intervention (i.e. package) and reporting neonatal morbidity or mortality
      outcomes were included. Studies were ordered by study design and mortality
      stratum, and their component interventions classified by time period of delivery
      and service delivery mode. We found 41 studies that implemented packages of
      interventions and reported neonatal health outcomes, including 19 randomized
      controlled trials. True effectiveness trials conducted at scale in health systems
      were completely lacking. No study targeted women prior to conception, antenatal
      interventions were largely micronutrient supplementation studies, and intrapartum
      interventions were limited principally to clean delivery. Few studies
      approximated complete packages recommended in The Lancet's Neonatal Survival
      Series. Interventions appeared largely bundled out of convenience or funding
      requirements, rather than based on anticipated synergistic effects, like service
      delivery mode or cost-effectiveness. Only two studies reported cost-effectiveness
      data. The evidence base for the impact of neonatal health intervention packages
      is a weak foundation for guiding effective implementation of public health
      programmes addressing neonatal health. Significant investment in effectiveness
      trials carefully tailored to local health needs and conducted at scale in
      developing countries is required.

PMID- 17526642
TI  - Genes misregulated in C. elegans deficient in Dicer, RDE-4, or RDE-1 are enriched
      for innate immunity genes.
AB  - We describe the first microarray analysis of a whole animal containing a mutation
      in the Dicer gene. We used adult Caenorhabditis elegans and, to distinguish among
      different roles of Dicer, we also performed microarray analyses of animals with
      mutations in rde-4 and rde-1, which are involved in silencing by siRNA, but not
      miRNA. Surprisingly, we find that the X chromosome is greatly enriched for genes
      regulated by Dicer. Comparison of all three microarray data sets indicates the
      majority of Dicer-regulated genes are not dependent on RDE-4 or RDE-1, including
      the X-linked genes. However, all three data sets are enriched in genes important
      for innate immunity and, specifically, show increased expression of innate
      immunity genes.

PMID- 17526643
TI  - Depletion of newly synthesized Argonaute1 impairs the RNAi response in
      Trypanosoma brucei.
AB  - In Trypanosoma brucei, Argonaute1 (TbAGO1) is an essential component of the RNA
      interference (RNAi) pathway. While characterizing a TbAGO1 conditional knockout
      cell line, we discovered that, upon blockage of TbAGO1 transcription, the RNAi
      response to transfected double-stranded RNA was severely inhibited, although
      there was no change in the TbAGO1 protein level. This observation suggested that
      steady-state TbAGO1 was not sufficient to fully support the RNAi response to
      transfected dsRNA and implicated newly synthesized Argonaute in this phenomenon.
      Indeed, a translational blockade of TbAGO1 mRNA with an antisense morpholino
      oligonucleotide resulted in inhibition of the RNAi response, even though the
      steady-state level of TbAGO1 remained unchanged during the time of the assay.
      Thus, we concluded that in T. brucei, newly synthesized TbAGO1 is required to
      support an efficient RNAi response. We speculate that newly processed siRNAs may
      be preferentially loaded onto newly synthesized TbAGO1, and this mechanism may
      contribute to the homeostasis of the RNAi pathway.

PMID- 17526644
TI  - Translation of the synaptonemal complex component Sycp3 is enhanced in vivo by
      the germ cell specific regulator Dazl.
AB  - DAZ-related genes are essential for gametogenesis in diverse metazoa: in human
      males, a loss of DAZ genes is associated with infertility. These genes, expressed
      only in germ cells, regulate the translation of a yet undefined set of specific
      transcripts, and loss of function results in numerous defects throughout the
      mitotic and meiotic process of germ cell development. In a mouse model, absence
      of the autosomal Dazl gene results in a final block at zygotene of meiotic
      prophase. Sycp3 is also essential for meiosis, specifically for the formation of
      the synaptonemal complex lateral element with a mouse knockout model displaying a
      block in meiotic prophase similar to the Dazl knock out. Sycp3 was identified as
      a potential target for translational regulation by Dazl in male mouse germ cells.
      This was confirmed by both RNA binding and translation assays. In the Dazl
      knockout mouse model, Sycp3 protein levels were decreased, indicating that Dazl
      is required for efficient translation of the Sycp3 mRNA in vivo. Taken together
      these data support Sycp3 as a biologically relevant target of Dazl-mediated
      translation in mammals. This suggests that azoospermia associated with a decrease
      in DAZ gene function in humans may in part be a consequence of failure at
      synapsis caused by reduced levels of SYCP3 protein.

PMID- 17526645
TI  - X-ray crystallographic and NMR studies of protein-protein and protein-nucleic
      acid interactions involving the KH domains from human poly(C)-binding protein-2.
AB  - Poly(C)-binding proteins (PCBPs) are KH (hnRNP K homology) domain-containing
      proteins that recognize poly(C) DNA and RNA sequences in mammalian cells. Binding
      poly(C) sequences via the KH domains is critical for PCBP functions. To reveal
      the mechanisms of KH domain-D/RNA recognition and its functional importance, we
      have determined the crystal structures of PCBP2 KH1 domain in complex with a 12
      nucleotide DNA corresponding to two repeats of the human C-rich strand telomeric
      DNA and its RNA equivalent. The crystal structures reveal molecular details for
      not only KH1-DNA/RNA interaction but also protein-protein interaction between two
      KH1 domains. NMR studies on a protein construct containing two KH domains (KH1 +
      KH2) of PCBP2 indicate that KH1 interacts with KH2 in a way similar to the KH1
      KH1 interaction. The crystal structures and NMR data suggest possible ways by
      which binding certain nucleic acid targets containing tandem poly(C) motifs may
      induce structural rearrangement of the KH domains in PCBPs; such structural
      rearrangement may be crucial for some PCBP functions.

PMID- 17526646
TI  - Progressive troponin I loss impairs cardiac relaxation and causes heart failure
      in mice.
AB  - Cardiac troponin I (TnI) knockout mice exhibit a phenotype of sudden death at 17
      18 days after birth due to a progressive loss of TnI. The objective of this study
      was to gain insight into the physiological consequences of TnI depletion and the
      cause of death in these mice. Cardiac function was monitored serially between 12
      and 17 days of age by using high-resolution ultrasonic imaging and Doppler
      echocardiography. Two-dimensional B-mode and anatomical M-mode imaging and
      Doppler echocardiography were performed using a high-frequency ( approximately 20
      45 MHz) ultrasound imaging system on homozygous cardiac TnI mutant mice (cTnI(-/
      )) and wild-type littermates. On day 12, cTnI(-/-) mice were indistinguishable
      from wild-type mice in terms of heart rate, atrial and LV (LV) chamber
      dimensions, LV posterior wall thickness, and body weight. By days 16 through 17,
      wild-type mice showed up to a 40% increase in chamber dimensions due to normal
      growth, whereas cTnI(-/-) mice showed increases in atrial dimensions of up to 97%
      but decreases in ventricular dimensions of up to 70%. Mitral Doppler analysis
      revealed prolonged isovolumic relaxation time and pronounced inversion of the
      mitral E/A ratio (early ventricular filling wave-to-late atrial contraction
      filling wave) only in cTnI(-/-) mice indicative of impaired LV relaxation. cTnI(
      /-) mouse hearts showed clear signs of failure on day 17, characterized by >50%
      declines in cardiac output, ejection fraction, and fractional shortening. B-mode
      echocardiography showed a profoundly narrowed tube-like LV and enlarged atria at
      this time. Our data are consistent with TnI deficiency causing impaired LV
      relaxation, which leads to diastolic heart failure in this model.

PMID- 17526647
TI  - Temporal and spatial variations of cell-free layer width in arterioles.
AB  - Separation of red blood cells and plasma in microcirculatory vessels produces a
      cell-free layer at the wall. This layer may be an important determinant of blood
      viscosity and wall shear stress in arterioles, where most of the hydraulic
      pressure loss in the circulatory system occurs and flow regulatory mechanisms are
      prominent. With the use of a newly developed method, the width of the cell-free
      layer was rapidly and repeatedly determined in arterioles (10- to 50-microm inner
      diameter) in the rat cremaster muscle at normal arterial pressure. The temporal
      variation of the cell-free layer width was non-Gaussian, but calculated mean and
      median values differed by <0.2 microm. The correlation length of the temporal
      variations downstream (an indication of mixing) was approximately 30 microm and
      was independent of pseudoshear rate (ratio of mean velocity to vessel diameter)
      and of vessel diameter. The cell-free layer width was significantly different on
      opposite sides of the vessel and inversely related. Increasing red blood cell
      aggregability reduced this inverse relation but had no effect on correlation
      length. In the diameter range studied, the mean width of the cell-free layer
      increased from 0.8 to 3.1 microm and temporal variations increased from 30% to
      70% of the mean width. Increased aggregability did not alter either relationship.
      In summary, the cell-free layer width in arterioles is diameter dependent and
      shows substantial non-Gaussian temporal variations. The temporal variations
      increase as diameter increases and are inversely related on opposite sides of the
      vessel.

PMID- 17526648
TI  - Intracellular renin-angiotensin system: the tip of the intracrine physiology
      iceberg.

PMID- 17526649
TI  - Ca(v)1.3 channels produce persistent calcium sparklets, but Ca(v)1.2 channels are
      responsible for sparklets in mouse arterial smooth muscle.
AB  - Ca(2+) sparklets are local elevations in intracellular Ca(2+) produced by the
      opening of a single or a cluster of L-type Ca(2+) channels. In arterial myocytes,
      Ca(2+) sparklets regulate local and global intracellular Ca(2+). At present, the
      molecular identity of the L-type Ca(2+) channels underlying Ca(2+) sparklets in
      these cells is undetermined. Here, we tested the hypotheses that voltage-gated
      calcium channel-alpha 1.3 subunit (Ca(v)1.3) can produce Ca(2+) sparklets and
      that Ca(v)1.2 and/or Ca(v)1.3 channels are responsible for Ca(2+) sparklets in
      mouse arterial myocytes. First, we investigated the functional properties of
      single Ca(v)1.3 channels in tsA201 cells. With 110 mM Ba(2+) as the charge
      carrier, Ca(v)1.3 channels had a conductance of 20 pS. This value is similar to
      that of Ca(v)1.2 and native L-type Ca(2+) channels. As previously shown for
      Ca(v)1.2 channels, Ca(v)1.3 channels can operate in two gating modes
      characterized by short and long open times. Expressed Ca(v)1.3 channels also
      produced Ca(2+) sparklets. Ca(v)1.3 sparklets had properties similar to those
      produced by Ca(v)1.2 and native L-type channels, including quantal amplitude,
      dihydropyridine sensitivity, bimodal gating, and dual-event duration times.
      However, the voltage dependencies of conductance and steady-state inactivation of
      the Ca(2+) current (I(Ca)) in arterial myocytes were similar to those recorded
      from cells expressing Ca(v)1.2 but not Ca(v)1.3 channels. Furthermore, nifedipine
      (10 microM) eliminated Ca(2+) sparklets in wild-type myocytes but not in myocytes
      expressing dihydropyridine-insensitive Ca(v)1.2 channels. Accordingly, Ca(v)1.3
      transcript and protein were not detected in isolated arterial myocytes. We
      conclude that although Ca(v)1.3 channels can produce Ca(2+) sparklets, Ca(v)1.2
      channels underlie I(Ca), Ca(2+) sparklets, and hence dihydropyridine-sensitive
      Ca(2+) influx in mouse arterial myocytes.

PMID- 17526650
TI  - Urocortin 1 administration from onset of rapid left ventricular pacing represses
      progression to overt heart failure.
AB  - Urocortin 1 (Ucn1) may be involved in the pathophysiology of heart failure (HF),
      but the impact of Ucn1 administration on progression of the disease is unknown.
      The aim of this study was to investigate the effects of Ucn1 in sheep from the
      onset of cardiac overload and during the subsequent development of HF. Eight
      sheep underwent two 4-day periods of HF induction by rapid left ventricular
      pacing (225 beats/min) in conjunction with continuous infusions of Ucn1 (0.1
      microg.kg(-1).h(-1) iv) and a vehicle control (0.9% saline). Compared with
      control, Ucn1 attenuated the pacing-induced decline in cardiac output (2.43 +/-
      0.46 vs. 3.70 +/- 0.89 l/min on day 4, P < 0.01) and increases in left atrial
      pressure (24.9 +/- 1.0 vs. 11.9 +/- 1.1 mmHg, P < 0.001) and peripheral
      resistance (38.7 +/- 9.4 vs. 25.2 +/- 6.1 mmHg.l(-1).min, P < 0.001). Ucn1 wholly
      prevented increases in plasma renin activity (4.02 +/- 1.17 vs. 0.87 +/- 0.1
      nmol.l(-1).h(-1), P < 0.001), aldosterone (1,313 +/- 324 vs. 413 +/- 174 pmol/l,
      P < 0.001), endothelin-1 (3.8 +/- 0.5 vs. 2.0 +/- 0.1 pmol/l, P < 0.001), and
      vasopressin (10.8 +/- 4.1 vs. 1.8 +/- 0.2 pmol/l, P < 0.05) during pacing alone
      and blunted the progressive increases in plasma epinephrine (2,132 +/- 697 vs.
      1,250 +/- 264 pmol/l, P < 0.05), norepinephrine (3.61 +/- 0.73 vs. 2.07 +/- 0.52
      nmol/l, P < 0.05), and atrial (P < 0.05) and brain (P < 0.01) natriuretic peptide
      levels. Ucn1 administration also maintained urine sodium excretion (0.75 +/- 0.34
      vs. 1.59 +/- 0.50 mmol/h on day 4, P < 0.05) and suppressed pacing-induced
      declines in creatinine clearance (P < 0.05). These findings indicate that Ucn1
      treatment from the onset of cardiac overload has the ability to repress the
      ensuing hemodynamic and renal deterioration and concomitant adverse neurohumoral
      activation, thereby delaying the development of overt HF. These data strongly
      support a use for Ucn1 as a therapeutic option early in the course of the
      disease.

PMID- 17526651
TI  - Muscarinic potassium channels augment dynamic and static heart rate responses to
      vagal stimulation.
AB  - Vagal control of heart rate (HR) is mediated by direct and indirect actions of
      ACh. Direct action of ACh activates the muscarinic K(+) (K(ACh)) channels,
      whereas indirect action inhibits adenylyl cyclase. The role of the K(ACh)
      channels in the overall picture of vagal HR control remains to be elucidated. We
      examined the role of the K(ACh) channels in the transfer characteristics of the
      HR response to vagal stimulation. In nine anesthetized sinoaortic-denerved and
      vagotomized rabbits, the vagal nerve was stimulated with a binary white-noise
      signal (0-10 Hz) for examination of the dynamic characteristic and in a step-wise
      manner (5, 10, 15, and 20 Hz/min) for examination of the static characteristic.
      The dynamic transfer function from vagal stimulation to HR approximated a first
      order, low-pass filter with a lag time. Tertiapin, a selective K(ACh) channel
      blocker (30 nmol/kg iv), significantly decreased the dynamic gain from 5.0 +/-
      1.2 to 2.0 +/- 0.6 (mean +/- SD) beats.min(-1).Hz(-1) (P < 0.01) and the corner
      frequency from 0.25 +/- 0.03 to 0.06 +/- 0.01 Hz (P < 0.01) without changing the
      lag time (0.37 +/- 0.04 vs. 0.39 +/- 0.05 s). Moreover, tertiapin significantly
      attenuated the vagal stimulation-induced HR decrease by 46 +/- 21, 58 +/- 18, 65
      +/- 15, and 68 +/- 11% at stimulus frequencies of 5, 10, 15, and 20 Hz,
      respectively. We conclude that K(ACh) channels contribute to a rapid HR change
      and to a larger decrease in the steady-state HR in response to more potent tonic
      vagal stimulation.

PMID- 17526652
TI  - Histidine-rich Ca-binding protein interacts with sarcoplasmic reticulum Ca
      ATPase.
AB  - Depressed cardiac Ca cycling by the sarcoplasmic reticulum (SR) has been
      associated with attenuated contractility, which can progress to heart failure.
      The histidine-rich Ca-binding protein (HRC) is an SR component that binds to
      triadin and may affect Ca release through the ryanodine receptor. HRC
      overexpression in transgenic mouse hearts was associated with decreased rates of
      SR Ca uptake and delayed relaxation, which progressed to hypertrophy with aging.
      The present study shows that HRC may mediate part of its regulatory effects by
      binding directly to sarco(endo)plasmic reticulum Ca-ATPase type 2 (SERCA2) in
      cardiac muscle, which is confirmed by coimmunostaining observed under confocal
      microscopy. This interaction involves the histidine- and glutamic acid-rich
      domain of HRC (320-460 aa) and the part of the NH(2)-terminal cation transporter
      domain of SERCA2 (74-90 aa) that projects into the SR lumen. The SERCA2-binding
      domain is upstream from the triadin-binding region in human HRC (609-699 aa).
      Specific binding between HRC and SERCA was verified by coimmunoprecipitation and
      pull-down assays using human and mouse cardiac homogenates and by blot overlays
      using glutathione S-transferase and maltose-binding protein recombinant proteins.
      Importantly, increases in Ca concentration were associated with a significant
      reduction of HRC binding to SERCA2, whereas they had opposite effects on the HRC
      triadin interaction in cardiac homogenates. Collectively, our data suggest that
      HRC may play a key role in the regulation of SR Ca cycling through its direct
      interactions with SERCA2 and triadin, mediating a fine cross talk between SR Ca
      uptake and release in the heart.

PMID- 17526653
TI  - Long-term effect of dietary {alpha}-linolenic acid or decosahexaenoic acid on
      incorporation of decosahexaenoic acid in membranes and its influence on rat heart
      in vivo.
AB  - The present study was designed to evaluate whether long-term intake of dietary
      alpha-linolenic acid (ALA), supplied as whole grain-extruded linseed, can
      increase endogenous production of n-3 long-chain polyunsaturated fatty acids
      (FAs) in healthy adult rats and influence the heart rate (HR) and adrenergic
      response in the same way as docosahexaenoic acid (DHA)-rich diets. DHA enrichment
      was evaluated using FA analysis of tissue phospholipids after 8, 16, 24, and 32
      wk of feeding in male Wistar rats randomly assigned to three dietary groups (n =
      8 in each group): a reference fat diet (RFD), an ALA-rich (ALA) diet, and a DHA
      rich (DHA) diet. At 1 wk before the animals were killed, under anesthesia, HR was
      measured from ECG recordings during an adrenergic stimulation challenge (n = 8).
      There was a significant increase of DHA in the cardiac membrane in the ALA group
      compared with the RFD group. DHA content in the cardiac membrane was
      approximately 10% in the ALA group vs. 20% in the DHA group and 4% in the RFD
      group. The cardiac FA profile was established after 2 mo and remained essentially
      unchanged thereafter. Regardless of the diet, DHA in the heart decreased with
      age. Nevertheless, DHA content in the heart remained at >15% in the DHA group and
      remained greater in older rats fed the ALA diet than in younger RFD-fed rats.
      Basal HR decreased in the ALA group (395 +/- 24.9 beats/min) to a level between
      that of the DHA and RFD groups (375 +/- 26.4 and 407 +/- 36.7 beats/min,
      respectively). Both n-3 dietary intakes contribute to enhancement of the
      chronotropic response to adrenergic agonist stimulation. Regulation of HR by
      neurohumoral mediators may be controlled by lower content of DHA, e.g., by a
      dietary supply of extruded linseed (ALA).

PMID- 17526654
TI  - Angiotensin II and endothelin-1 augment the vascular complications of diabetes
      via JAK2 activation.
AB  - The JAK/STAT pathway is activated in vitro by angiotensin II (ANG II) and
      endothelin-1 (ET-1), which are implicated in the development of diabetic
      complications. We hypothesized that ANG II and ET-1 activate the JAK/STAT pathway
      in vivo to participate in the development of diabetic vascular complications.
      Using male Sprague-Dawley rats, we performed a time course study [days 7, 14, and
      28 after streptozotocin (STZ) injection] to determine changes in phosphorylation
      of JAK2, STAT1, and STAT3 in thoracic aorta using standard Western blot
      techniques. On day 7 there was no change in phosphorylation of JAK2, STAT1, and
      STAT3. Phosphorylation of JAK2, STAT1, and STAT3 was significantly increased on
      days 14 and 28 and was inhibited by treatment with candesartan (AT(1) receptor
      antagonist, 10 mg x kg(-1) x day(-1) orally in drinking water), atrasentan (ET(A)
      receptor antagonist, 10 mg x kg(-1) x day(-1) orally in drinking water), and AG
      490 (JAK2 inhibitor, 5 mg x kg(-1) x day(-1) intraperitoneally). On day 28,
      treatment with all inhibitors prevented the significant increase in systolic
      blood pressure (SBP; tail cuff) of STZ-induced diabetic rats (SBP: 157 +/- 9.0,
      130 +/- 3.3, 128 +/- 6.8, and 131 +/- 10.4 mmHg in STZ, STZ-candesartan, STZ
      atrasentan, and STZ-AG-490 rats, respectively). In isolated tissue bath studies,
      diabetic rats displayed impaired endothelium-dependent relaxation in aorta
      (maximal relaxation: 95.3 +/- 3.0, 92.6 +/- 7.4, 76.9 +/- 12.1, and 38.3 +/-
      13.1% in sham, sham + AG-490, STZ + AG-490, and STZ rats, respectively).
      Treatment of rats with AG-490 restored endothelium-dependent relaxation in aorta
      from diabetic rats at 14 and 28 days of treatment. These results demonstrate that
      JAK2 activation in vivo participates in the development of vascular complications
      associated with STZ-induced diabetes.

PMID- 17526655
TI  - Influence of sex, high-fat diet, and exercise training on potassium currents of
      swine coronary smooth muscle.
AB  - Potassium channels in vascular smooth muscle (VSM) control vasodilation and are
      potential regulatory targets. This study evaluated effects of sex differences,
      exercise training (EX), and high-fat diet (HF) on K(+) currents (I(K)) of
      coronary VSM cells. Yucatan male and female swine were assigned to either
      sedentary confinement (SED), 16 wk of EX, 20 wk of HF, or 20 wk of HF with 16 wk
      of EX (HF-EX). VSM cells of normal-diet SED animals exhibited three components of
      I(K): 4-aminopyridine-sensitive I(K(KV)), TEA-sensitive I(K(BK)), and 4
      aminopyridine + TEA-insensitive I(K). Females exhibited significantly higher
      basal I(K) than males in the same group. EX increased basal I(K) in males and
      females. HF reduced I(K) in males and females and nullified effects of EX.
      Endothelin-1 increased I(K) significantly in males but not in females. In the
      presence of endothelin-1, 1) I(K(KV)) was similar in SED males and females and EX
      increased I(K(KV)) to a greater extent in males than in females and 2) I(K(BK))
      was greater in SED females than in males and EX increased I(K(BK)) to a greater
      extent in males, resulting in I(K(BK)) similar to EX females. Importantly, HF
      nullified effects of EX on I(K(KV)) and I(K(BK)). These data indicate that basal
      I(K) of SED female swine is inherently greater than that shown in SED males and
      that males require EX to achieve comparable levels of I(K). Importantly, HF
      reduced I(K) in males and females and nullified effects of EX, suggesting HF
      abrogates beneficial effects of EX on coronary smooth muscle.

PMID- 17526656
TI  - Cardioprotective effects of nitric oxide-aspirin in myocardial ischemia
      reperfused rats.
AB  - In this study, the cardioprotective effects of nitric oxide (NO)-aspirin, the
      nitroderivative of aspirin, were compared with those of aspirin in an
      anesthetized rat model of myocardial ischemia-reperfusion. Rats were given
      aspirin or NO-aspirin orally for 7 consecutive days preceding 25 min of
      myocardial ischemia followed by 48 h of reperfusion (MI/R). Treatment groups
      included vehicle (Tween 80), aspirin (30 mg.kg(-1).day(-1)), and NO-aspirin (56
      mg.kg(-1).day(-1)). NO-aspirin, compared with aspirin, displayed remarkable
      cardioprotection in rats subjected to MI/R as determined by the mortality rate
      and infarct size. Mortality rates for vehicle (n = 23), aspirin (n = 22), and NO
      aspirin groups (n = 22) were 34.8, 27.3, and 18.2%, respectively. Infarct size of
      the vehicle group was 44.5 +/- 2.7% of the left ventricle (LV). In contrast,
      infarct size of the LV decreased in the aspirin- and NO-aspirin-pretreated
      groups, 36.7 +/- 1.8 and 22.9 +/- 4.3%, respectively (both P < 0.05 compared with
      vehicle group; P < 0.05, NO-aspirin vs. aspirin ). Moreover, NO-aspirin also
      improved ischemia-reperfusion-induced myocardial contractile dysfunction on
      postischemic LV developed pressure. In addition, NO-aspirin downregulated
      inducible NO synthase (iNOS; 0.37-fold, P < 0.01) and cyclooxygenase-2 (COX-2;
      0.61-fold, P < 0.05) gene expression compared with the vehicle group after 48 h
      of reperfusion. Treatment with N(G)-nitro-L-arginine methyl ester (L-NAME; 20
      mg/kg), a nonselective NOS inhibitor, aggravated myocardial damage in terms of
      mortality and infarct size but attenuated effects when coadministered with NO
      aspirin. L-NAME administration did not alter the increase in iNOS and COX-2
      expression but did reverse the NO-aspirin-induced inhibition of expression of the
      two genes. The beneficial effects of NO-aspirin appeared to be derived largely
      from the NO moiety, which attenuated myocardial injury to limit infarct size and
      better recovery of LV function following ischemia and reperfusion.

PMID- 17526657
TI  - Investigating the relationship between the prion protein locus and udder
      morphology traits and milk yield in Sardinian sheep.
AB  - Different approaches were applied to investigate prion protein (PrP)-encoding
      gene effects on udder morphology and milk yield in Sardinian sheep. The PrP
      genotype of 23,077 animals (10,029 males) was determined. The direct effect of
      the PrP or a closely linked gene was analyzed at the population-wide level using
      2 animal models, based on records from genotyped animals, including only the PrP
      genotype as a fixed effect. In the female model, the dependent variable was
      animal performance deviation, calculated as the sum of the individual random
      effects. The male model was based on daughter yield deviations. Both dependent
      variables were obtained from the national genetic evaluations of 2005. The
      significance of pairwise comparisons between genotypes was assessed by using the
      Tukey-Kramer multiple-comparison procedure. Within-family analyses were performed
      on sires heterozygous for the PrP gene to detect those genes that affect the
      traits of interest and are not in linkage disequilibrium with the PrP locus at
      the population-wide level. The overall results led us to exclude either a direct
      or a linkage gene effect of the PrP locus on udder morphology or milk yield in
      Sardinian sheep. A further analysis of males that neglected the relationship
      matrix was carried out to evaluate the effect on the loss of genetic gain of the
      different selection pressures applied on resistant and susceptible genotype
      classes. Significant differences between genotypes were detected for milk yield.
      These were due to the different selection pressures applied to the PrP genotype
      classes. Finally, no negative correlated genetic response on the selection traits
      is expected from the selection for scrapie resistance in the Sardinian breed.
      However, a loss of genetic gain for milk yield is likely to occur in the future
      due to the different selection pressures on resistant and susceptible males.

PMID- 17526658
TI  - Utilization of dried distillers grains for developing beef heifers.
AB  - A 2-yr study was conducted at 2 locations to determine if supplementing beef
      heifers with dried distillers grains (DDG) as an energy source affected growth or
      reproduction. Spring-born crossbred heifers (n = 316) were blocked by age or sire
      and age and assigned randomly to DDG or control (dried corn gluten feed, whole
      corn germ, urea) supplement. Heifers received prairie hay in amounts sufficient
      for ad libitum intake and 0.59% of BW DDG or 0.78% of BW control supplement (DM
      basis). Supplements were formulated to be isocaloric, but protein degradability
      differed. Supplemental undegradable intake protein intake from DDG averaged 267
      g/animal daily and reached 318 g/animal daily; control supplemental undegradable
      intake protein intake averaged 90 g/animal daily and peaked at 107 g/animal
      daily. Initial pubertal status was determined by 2 blood samples collected 10 d
      apart, and monthly BW were collected from November through January; then biweekly
      BW and blood samples were collected from February until May yearly. Heifers were
      synchronized with 2 injections of PGF2alpha 14 d apart; estrus was detected and
      heifers were artificially inseminated for 5 d and placed with bulls 10 d later.
      Conception and pregnancy rates were determined via transrectal ultrasonography.
      Initial age, BW, and BCS did not differ (P > 0.92) for control and DDG heifers.
      Final BW, ADG, and final BCS also were not affected (P > 0.31) by
      supplementation. Estimated age and BW at puberty did not differ (P > 0.23)
      between treatments, and the proportions of pubertal heifers did not differ at the
      initiation of the experiment (P > 0.82), at the beginning of the 14-d sampling
      intervals, or before synchronization. Estrus synchronization rate (75.9%), time
      of estrus, and overall pregnancy rate (89.5%) were not affected (P > 0.14) by
      treatment. However, a greater proportion (P = 0.008) of DDG than control heifers
      conceived to AI (75.0 vs. 52.9%), resulting in greater (P = 0.07) AI pregnancy
      rates for DDG heifers (57.0 vs. 40.1%). Body weight or BCS at pregnancy diagnosis
      did not differ (P > 0.52) between DDG and control heifers. Supplementing beef
      heifers with DDG during development did not affect age at puberty but improved AI
      conception and pregnancy rates compared with an isocaloric control supplement.

PMID- 17526659
TI  - Changes in small intestinal nutrient transport and barrier function after
      lipopolysaccharide exposure in two pig breeds.
AB  - Specific pig breeds with unique characteristics have been developed, and the
      current study sought to characterize some of these differences. Using modified
      Ussing chambers, electrophysiological mucosal transport of D-glucose, L-Gln, L
      Pro, L-Arg, L-Thr, and glycylsarcosine was assessed in small intestinal tissues
      (duodenum, jejunum, ileum) taken from Yorkshire-based hybrid (BW = 142.4 +/- 2.0
      kg; mean age = 8 mo) and Meishan (BW = 65.8 +/- 0.8 kg; mean age = 6 mo) female
      pigs after 4 h of lipopolysaccharide (LPS) exposure. Gilts were randomly assigned
      to control (saline infusion; n = 6 Yorkshires, n = 5 Meishans) or LPS (n = 7
      Yorkshires, n = 5 Meishans) groups. Therefore, treatments were arranged in a 2
      (breed) x 2 (LPS infusion) factorial. Four hours after infusions, pigs were
      euthanized, and intestinal segment samples were removed. Glucose transport in the
      ileum was decreased (P < 0.001) in Yorkshires with LPS but was increased (P <
      0.001) by over 2-fold in Meishans with LPS. After LPS infusion, Pro transport was
      increased in duodenum (over 5-fold; P = 0.04) and ileum (over 10-fold; P < 0.001)
      of Meishans but was unaffected in Yorkshires. Arginine transport in the ileum of
      control Meishans was greater (P = 0.05) than Arg transport in control Yorkshires.
      Glycylsarcosine transport was greater (P = 0.02) in Meishans than Yorkshires
      (nearly 2-fold), regardless of LPS provision. Glycylsarcosine transport was
      increased (P = 0.003) over 2-fold by LPS, regardless of pig breed. Resistance
      (barrier function) was increased (P = 0.03) by LPS in Yorkshires but was
      unaffected in Meishans. The current study indicates that small intestinal
      function responded differently to LPS in Yorkshire and Meishan gilts and that
      these effects were nutrient- and segment-dependent.

PMID- 17526660
TI  - Postprandial kinetics of some biotic and abiotic characteristics of the gastric
      ecosystem of horses fed a pelleted concentrate meal.
AB  - Our knowledge of the microflora of the stomach of the horse is still limited,
      although some data indicate its important role in nutrition. The objective of
      this experiment was to investigate the microbial and biochemical profiles in the
      stomach of the horse and to quantify the disappearance of dietary starch. Total
      anaerobic bacteria, lactate-utilizing bacteria, lactobacilli, and streptococci
      were determined, and biochemical characteristics (pH, and DM, D- and L-lactate, D
      glucose, NH3, and VFA concentrations) were measured in chyme collected from 4
      horses by naso-gastric intubation aided by endoscopy, at 30 min before and 60,
      120, and 210 min after the meal. The total anaerobic population exhibited a
      linear increase (5.54 to 6.98 log10 cfu/mL; P = 0.018) within the first
      postprandial hour and reached 8.32 log10 cfu/mL at 210 min after the meal. The
      concentrations of lactobacilli, streptococci, and lactate-utilizing bacteria in
      the stomach contents were 5.52, 4.82, and 6.95 log10 cfu/mL, respectively.
      Lactate concentration increased linearly from 0.25 mmol/L before the meal to 7.98
      mmol/L at the last collection point (P = 0.013). This increase was mostly due to
      L-lactate accumulation. The VFA concentration increased linearly (P = 0.002)
      during the postprandial period from 1.96 to 8.17 mmol/L. Acetate represented, on
      average, 78 mol/100 mol of total VFA. The average concentration of NH3 in the
      stomach content was 2.48 mmol/L. Dietary starch disappearance did not respond
      during the post-prandial period and was not consistent with previous findings.
      These in vivo data provide complementary information on the postprandial
      microbial and biochemical kinetics in the stomachs of horses and confirm its
      abundant microbial colonization.

PMID- 17526661
TI  - Cow and calf performance on Coastal or Tifton 85 Bermudagrass pastures with
      aeschynomene creep-grazing paddocks.
AB  - Cow and calf performance was determined in a 2-yr, 2 x 2 factorial, grazing
      experiment using Coastal or Tifton 85 (T85) replicated Bermudagrass pastures (4
      pastures each; each pasture 4.86 ha), without or with aeschynomene creep-grazing
      paddocks (n = 4, 0.202 ha each, planted in May of each year, 13.44 kg/ha). On
      June 10, 2004, and June 8, 2005, 96 winter-calving beef "tester" cows and their
      calves were grouped by cow breed (9 Angus and 3 Polled Hereford/group), initial
      cow BW (592.9 +/- 70.1 kg, 2-yr mean), age of dam, calf breed (Angus, Polled
      Hereford, or Angus x Polled Hereford), calf sex, initial calf age (117 +/- 20.1
      d, 2-yr mean), and initial calf BW (161.3 +/- 30.4 kg) and were randomly assigned
      to pastures. Additional cow-calf pairs and open cows were added as the forage
      increased during the season. Forage mass was similar for all treatment pastures
      (P > 0.70; 2-yr mean, 6,939 vs. 6,628 kg/ha, Coastal vs. T85; 6,664 vs. 6,896
      kg/ha, no creep grazing vs. creep grazing). Main effect interactions did not
      occur for performance variables (P > 0.10; 2-yr means), and year affected only
      the initial and final BW of the calves and cows. The 91-d tester calf ADG was
      greater for calves grazing T85 than Coastal (0.94 vs. 0.79 kg; P < 0.01), and for
      calves creep grazing aeschynomene compared with calves without creep grazing
      (0.90 vs. 0.82 kg; P < 0.03). Calf 205-d adjusted weaning weights were increased
      for calves grazing T85 compared with Coastal (252.9 vs. 240.3 kg; P < 0.01) and
      for calves with access to creep grazing (249.9 vs. 243.3 kg; P < 0.05). The IVDMD
      of esophageal masticate from pastures had a forage x creep grazing interaction (P
      < 0.05; Coastal, no creep grazing = 57.4%; Coastal, creep grazing = 52.1%; T85,
      no creep grazing = 59.1%; T85, creep grazing = 60.0%), and IVDMD was greater (P <
      0.05) for T85 than for Coastal pastures. Cows were milked in August 2004, and in
      June and August 2005, with variable milk yields on treatments, but increased milk
      protein (P < 0.05) for cows grazing T85 compared with Coastal pastures in August
      each year, contributing to increased calf gains on T85 pastures. These results
      complement previous research with T85 and indicate increased forage quality and
      performance of cattle grazing T85 pastures. Calf gains on T85 pastures and for
      calves on creep-grazed aeschynomene paddocks were high enough to influence the
      efficiency of cow-calf operations.

PMID- 17526662
TI  - Genetic and phenotypic relationships of feed intake and measures of efficiency
      with growth and carcass merit of beef cattle.
AB  - Feed intake and efficiency of growth are economically important traits of beef
      cattle. This study determined the relationships of daily DMI, feed:gain ratio
      [F:G, which is the reciprocal of the efficiency of gain (G:F) and therefore
      increases as the efficiency of gain decreases and vice versa, residual feed
      intake (RFI), and partial efficiency of growth (efficiency of ADG, PEG) with
      growth and carcass merit of beef cattle. Residual feed intake was calculated from
      phenotypic regression (RFIp) or genetic regression (RFIg) of ADG and metabolic BW
      on DMI. An F1 half-sib pedigree file containing 28 sires, 321 dams, and 464
      progeny produced from crosses between Alberta Hybrid cows and Angus, Charolais,
      or Alberta Hybrid bulls was used. Families averaged 20 progeny per sire (range =
      3 to 56). Performance, ultrasound, and DMI data was available on all progeny, of
      which 381 had carcass data. Phenotypic and genetic parameters were obtained using
      SAS and ASREML software, respectively. Differences in RFIp and RFIg,
      respectively, between the most and least efficient steers (i.e., steers with the
      lowest PEG) were 5.59 and 6.84 kg of DM/d. Heritabilities for DMI, F:G, PEG,
      RFIp, and RFIg were 0.54 +/- 0.15, 0.41 +/- 0.15, 0.56 +/- 0.16, 0.21 +/- 0.12,
      and 0.42 +/- 0.15, respectively. The genetic (r = 0.92) and phenotypic (r = 0.97)
      correlations between RFIp and RFIg indicated that the 2 indices are very similar.
      Both indices of RFI were favorably correlated phenotypically (P < 0.001) and
      genetically with DMI, F:G, and PEG. Residual feed intake was tendentiously
      genetically correlated with ADG (r = 0.46 +/- 0.45) and metabolic BW (r = 0.27 +/
      0.33), albeit with high SE. Genetically, RFIg was independent of ADG and BW but
      showed a phenotypic correlation with ADG (r = -0.21; P < 0.05). Daily DMI was
      correlated genetically (r = 0.28) and phenotypically (r = 0.30) with F:G. Both
      DMI and F:G were strongly correlated with ADG (r > 0.50), but only DMI had strong
      genetic (r = 0.87 +/- 0.10) and phenotypic (r = 0.65) correlations with metabolic
      BW. Generally, the phenotypic and genetic correlations of RFI with carcass merit
      were not different from zero, except genetic correlations of RFI with ultrasound
      and carcass LM area and carcass lean yield and phenotypic correlations of RFI
      with backfat thickness (P < 0.01). Daily DMI had moderate to high phenotypic (P <
      0.01) and genetic correlations with all the ultrasound and carcass traits.
      Depending on how RFI technology is applied, adjustment for body composition in
      addition to growth may be required to minimize the potential for correlated
      responses to selection in cattle.

PMID- 17526663
TI  - Plasma diamine oxidase: a biomarker of copper deficiency in the bovine.
AB  - This study was designed to test the efficacy of plasma diamine oxidase (DAO)
      activity as a biomarker of Cu deficiency in the bovine. Angus steers (n = 11) and
      heifers (n = 17) were assigned to 1 of 3 treatments: 1) control (adequate dietary
      Cu), 2) Cu-deficient (-Cu), and 3) Cu-deficient plus high dietary Mn (-Cu+Mn),
      and fed from weaning through finishing. Molybdenum (2 mg/kg of DM) was
      supplemented to treatments -Cu and -Cu+Mn to induce Cu deficiency via the
      formation of ruminal thiomolybdates. Samples were collected on 2 sampling dates
      (d 160 and 190) to determine the efficacy of plasma DAO activity as a biomarker
      of Cu deficiency. For both sampling dates, liver Cu, plasma Cu, and plasma
      ceruloplasmin activity indicated that cattle receiving diets designed to induce
      Cu deficiency (-Cu and -Cu+Mn) were Cu-deficient, with all indices of Cu status
      lower (P < 0.001) than the control animals. In addition to these traditional
      indices of Cu status, plasma DAO activity also effectively identified Cu
      deficient animals because plasma DAO levels were reduced (P < 0.001) by 2- to 3
      fold compared with controls. Correlation analysis indicated that plasma DAO
      activity was highly correlated to all other indices of Cu status (Pearson R =
      0.73 to 0.87). During the growing phase, ADG (P = 0.09) and G:F (P = 0.002) were
      depressed in Cu-deficient animals compared with controls, whereas cattle
      performed equally well across all treatments in the finishing phase. The plasma
      DAO activity assay was precise and reliable based on an intraassay CV of 4.4% and
      interassay CV of 11.1%. Due to increased variability, freezing and thawing of
      plasma samples resulted in significant changes in DAO activity relative to fresh
      plasma DAO activity values. Thus, fresh plasma DAO activity, a relatively simple
      assay, may serve as an effective tool to diagnose Cu deficiency in the bovine.

PMID- 17526664
TI  - Influence of surfactant supplementation and maceration on the feeding value of
      rice straw in growing-finishing diets for Holstein steers.
AB  - Two trials were conducted to evaluate the interaction of the maceration process
      and surfactant (Tween 80) supplementation on feeding value of rice straw.
      Treatments were steam-flaked, corn-based diets containing 14% forage (DM basis),
      which was 1) Sudangrass hay; 2) ground rice straw; 3) ground rice straw plus
      0.22% Tween 80; 4) macerated rice straw; and 5) macerated rice straw plus 0.22%
      Tween 80. In the maceration process, rice straw was passed through 2 sequentially
      placed pairs of corrugated rolls set at zero tolerance under a ram pressure of
      62,050 millibars, similar to a conventional grain roller mill, except that the
      opposing rolls operated at different speeds (12 and 14 rpm, respectively).
      Sudangrass hay and rice straw (native and macerated) were ground through a 2.6-cm
      screen before incorporation into complete mixed diets. In trial 1, 125 Holstein
      steers (292 +/- 1.7 kg of BW) were used in a 188-d evaluation of the treatment
      effects on growth performance and carcass characteristics. In trial 2, 5 Holstein
      steers (224 +/- 3.5 kg of BW) with cannulas in the rumen and proximal duodenum
      were used in a 5 x 5 Latin square design to evaluate the treatment effects on
      digestion. There were no interactions between maceration and surfactant on growth
      or carcass characteristics. Tween 80 did not influence the feeding value of rice
      straw. Compared with grinding alone, maceration of rice straw increased the
      carcass-adjusted ADG (6%, P < 0.10), G:F (6%, P < 0.05), and dietary NE (5%, P <
      0.05); DMI was similar across treatments. Assuming NE(m) and NE(g) of Sudangrass
      hay are 1.18 and 0.62 Mcal/kg, the NE(m) and NE(g) were 0.61 and 0.13 Mcal/kg for
      ground rice straw and 1.21 and 0.65 Mcal/kg for macerated rice straw. There were
      no treatment interactions on characteristics of digestion. Tween 80 did not
      influence ruminal or total tract digestion of OM, starch, NDF, or N. Compared
      with grinding alone, maceration of rice straw increased ruminal digestion of OM
      (7.7%, P < 0.10) and NDF (30.8%, P < 0.05), and total tract digestion of OM
      (2.3%, P < 0.10), NDF (21.1%, P < 0.01), and N (3.7%, P < 0.05). Total tract
      digestion of OM, NDF, starch, and N for the Sudangrass diet corresponded closely
      with that of the macerated rice straw diets. Maceration increases the feeding
      value of rice straw to a level similar to that of good-quality (flag stage of
      maturity) Sudangrass hay, which is attributable to increased OM and NDF
      digestion. Effects of surfactant supplementation on growth performance and
      digestion are not appreciable.

PMID- 17526665
TI  - Effect of distillers grains or corn supplementation frequency on forage intake
      and digestibility.
AB  - Ten ruminally cannulated heifers (BW = 416 kg; SD = 24) were used to test the
      effect of the form and frequency of supplemental energy on forage DMI and
      digestibility. Five treatments were arranged in a replicated, 5 x 4 Latin
      rectangle (n = 8), and included no supplement (control), dry-rolled corn (DRC)
      fed daily, DRC fed on alternate days (DRC-A), dried distillers grains plus
      solubles (DDGS) fed daily, and DDGS fed on alternate days (DDGS-A). Supplements
      fed daily were fed at 0.40% of BW, whereas alternate day-fed supplements were fed
      at 0.80% of BW every other day. Chopped grass hay (8.2% CP) was fed to allow ad
      libitum DMI, and the intake pattern was measured. Control heifers had greater (P
      < 0.01) hay DMI than supplemented heifers (1.88 vs. 1.66% of BW daily,
      respectively), although total DMI was lower (P < 0.01) for control. Hay DMI did
      not differ (P = 0.45) between DRC and DDGS, and tended to be lower (P = 0.08) by
      heifers on DDGS-A and DRC-A than by heifers supplemented daily. Hay intake was
      lower (P < 0.01) on supplementation days for DDGS-A and DRC-A than on
      nonsupplemented days. Heifers in alternate-day treatments had fewer (P < 0.01)
      and larger (P < 0.01) meals and spent less (P < 0.01) time eating than those
      supplemented daily. Average rumen pH was greater (P = 0.05) for control than
      supplemented heifers (6.30 vs. 6.19). Control heifers had greater (P = 0.04)
      rates and extents of NDF disappearance than supplemented heifers. Rate of hay NDF
      disappearance was lower (P = 0.02) for DRC than for DDGS. Supplementation
      decreased hay DMI and changed digestion kinetics. Supplementation frequency
      affected amount and pattern of DMI. Rate of hay NDF disappearance was greater for
      DDGS than DRC.

PMID- 17526666
TI  - Influence of endosperm vitreousness and kernel moisture at harvest on site and
      extent of digestion of high-moisture corn by feedlot steers.
AB  - Six ruminally and duodenally cannulated Angus-Jersey crossbred steers (450 kg of
      BW) were used in a 6 x 6 Latin square to evaluate the effect of kernel
      vitreousness and moisture on intake and digestibility of high-moisture corn.
      Arranged in a 2 x 3 factorial, diets included a floury (FLO) or a vitreous (VIT)
      endosperm corn hybrid harvested at 28.1% (DRY), 31.2% (MID), or 35.7% (WET)
      kernel moisture content. Diet DM consisted of 88.25% high-moisture corn, 6%
      chopped alfalfa hay, 2% corn gluten meal, 0.75% urea, and 3% supplement.
      Supplement was included to ensure that the diets contained a minimum (DM basis)
      of 0.6% Ca, 0.6% K, 0.2% S, 33 mg/kg of monensin, and 11 mg/kg of tylosin.
      Geometric mean diameter of lyophilized high-moisture corn tended to be less (P =
      0.06) for VIT than for FLO, and the calculated particle surface area was 15.8%
      greater (P = 0.03). An interaction of vitreousness with the quadratic effect of
      moisture was noted (P < 0.001), such that fraction a and effective degradation
      for starch tended to be greater for the vitreous hybrid at the least and greatest
      moisture content but lower for the vitreous hybrid at the intermediate moisture
      content. Intake and ruminal disappearance of DM, OM, and starch were not
      influenced by vitreousness or moisture, with ruminal starch disappearance
      averaging 90.9%. Intestinal starch digestion measured as a percentage of starch
      entering the intestines averaged 91% and was greater (P < 0.05) for VIT than FLO
      corn. Averaged across moisture levels, total tract starch digestibility was
      greater (P < 0.003) for VIT than FLO. Compared with FLO kernels, VIT kernels
      appeared to be more brittle and therefore shattered more readily when rolled,
      particularly at the driest kernel moisture level. Furthermore, increased surface
      area of smaller particles may have been responsible for the greater starch
      utilization from VIT corn. In contrast with the results from other in situ and in
      vivo trials with dry-rolled corn grain, in which the starch from vitreous hybrids
      was less rapidly or completely digested, hybrids with more vitreous starch, when
      fed as high-moisture corn, had greater total tract starch digestibility,
      primarily due to greater postruminal starch digestion.

PMID- 17526667
TI  - A study of the factors that influence consumer attitudes toward beef products
      using the conjoint market analysis tool.
AB  - This study utilizes an analysis technique commonly used in marketing, the
      conjoint analysis method, to examine the relative utilities of a set of beef
      steak characteristics considered by a national sample of 1,432 US consumers, as
      well as additional localized samples representing undergraduate students at a
      business college and in an animal science department. The analyses indicate that
      among all respondents, region of origin is by far the most important
      characteristic; this is followed by animal breed, traceability, animal feed, and
      beef quality. Alternatively, the cost of cut, farm ownership, the use (or nonuse)
      of growth promoters, and whether the product is guaranteed tender were the least
      important factors. Results for animal science undergraduates are similar to the
      aggregate results, except that these students emphasized beef quality at the
      expense of traceability and the nonuse of growth promoters. Business students
      also emphasized region of origin but then emphasized traceability and cost. The
      ideal steak for the national sample is from a locally produced, choice Angus fed
      a mixture of grain and grass that is traceable to the farm of origin. If the
      product was not produced locally, respondents indicated that their preferred
      production states are, in order from most to least preferred, Iowa, Texas,
      Nebraska, and Kansas.

PMID- 17526668
TI  - Effect of yeast culture on in vitro fermentation of a high-concentrate or high
      fiber diet using equine fecal inoculum in a Daisy II incubator.
AB  - Two experiments were conducted to evaluate the use of a closed system,
      fermentation apparatus (Daisy II incubator) and determine the effects of a yeast
      culture (YC) preparation (Saccharomyces cerevisiae) on in vitro microbial
      populations, diet digestion, and fermentation patterns in horses. In Exp. 1, 4
      mature horses were fed a pelleted concentrate and alfalfa cubes in a 50:50 (%, as
      fed) ratio. Fecal samples were taken from each horse to form the inoculum and
      placed in 4 separate incubation vessels. Twenty nylon bags (10 with 0.25 g and 10
      with 0.50 g of the total mixed diet) were placed in each vessel, and in vitro
      fermentation was carried out for 48 h to determine DM, NDF, and ADF
      digestibility. In Exp. 2, fecal samples were taken from 4 mature horses consuming
      either a high-concentrate (HC) or high-fiber (HF) diet. Filter bags containing
      the HC or HF diet were added to the 4 incubation vessels along with their
      respective inoculums. Yeast culture was added to 2 of the vessels containing the
      HC or HF diet, whereas the other 2 vessels served as controls. Vessels were
      incubated as in Exp. 1 with samples taken at 24 and 48 h. Filter bags were used
      to determine DM, NDF, ADF, and OM digestibility, whereas vessel fluid was
      analyzed for lactate, ammonia, VFA, and microbial concentrations. Results of Exp.
      1 indicated that DM, NDF, and ADF digestibility were greater (P < 0.05), whereas
      the corresponding CV was lower (P < 0.05) for the 0.25- vs. the 0.50-g sample
      size. In Exp. 2, YC tended (P = 0.10) to decrease ammonia concentrations in the
      HF diet and increased (P < 0.05) acetate production in the HC diet when compared
      with the control. There were no effects of YC on pH, lactate, or the measured
      microbial populations, as well as DM, NDF, or ADF digestibility. The results did,
      however, show that in vitro and in vivo DM digestibility estimates were similar
      within a diet. Data from Exp. 1 indicated that the 0.25-g sample size provides a
      more accurate estimate of DM digestibility with less variation. Although YC had
      little, if any, effect in Exp. 2, the results indicated that the Daisy II
      incubator does provide valid estimates of total tract DM digestibility in the
      horse. These data provide further evidence that this process would be an
      effective and practical means of approximating the digestibility of diets with
      varying concentrate to forage ratios.

PMID- 17526669
TI  - Effects of supplement type on performance, reproductive, and physiological
      responses of Brahman-crossbred females.
AB  - Two experiments were conducted to compare the performance and physiological
      responses of forage-fed beef females supplemented with either a molasses-based
      (ML) or a citrus pulp-based (CT) supplement. In Exp. 1, BW gain, reproductive
      performance, and concentrations of blood urea N (BUN), plasma glucose, insulin,
      IGF-I, and progesterone (P4) were assessed in 60 Brahman x Angus heifers
      supplemented 3 times weekly with either ML or CT. Supplement intakes were
      formulated to be isocaloric and isonitrogenous. Reproductive performance was not
      affected by treatments, but mean BW gain was greater (P < 0.01) for heifers fed
      CT than for those fed ML (0.40 vs. 0.30 kg/d). Mean plasma concentrations of
      glucose, insulin, and IGF-I were greater (P < 0.05) for heifers fed CT, whereas
      BUN was greater (P < 0.05) for heifers fed ML. Mean plasma P4 concentration did
      not differ between treatments, but both groups had lower plasma P4 concentrations
      during days that supplements were offered (P < 0.01). In Exp. 2, forage DMI and
      concentrations of BUN, plasma glucose, insulin, IGF-I, and P4 were assessed in 24
      Brahman x British mature cows supplemented with the same treatments described in
      Exp. 1. Overall forage DMI did not differ between treatments, but a day effect
      and a treatment x day interaction were detected (P < 0.05). Both groups consumed
      less forage during the days on which the supplements were offered (P < 0.01), and
      forage DMI for cows fed CT was less (P < 0.05) than for cows fed ML during those
      days. No differences were detected in any blood or plasma measurement. In
      addition, no differences in concentrations of P4 were detected between CT- and ML
      fed cows. We concluded that CT-supplemented heifers had greater BW gain compared
      with ML-supplemented heifers, but no differences in reproductive performance were
      observed. We also observed that CT-supplemented cows had a greater variability in
      forage DMI compared with ML-supplemented cows.

PMID- 17526670
TI  - Optimizing nitrogen utilization in growing steers fed forage diets supplemented
      with dried citrus pulp.
AB  - Our objectives were to compare the effects of sources of supplemental N on
      ruminal fermentation of dried citrus pulp (DCP) and performance of growing steers
      fed DCP and bahiagrass (Paspalum notatum) hay. In Exp. 1, fermentation of DCP
      alone was compared with that of isonitrogenous mixtures of DCP and solvent
      soybean meal (SBM), expeller soybean meal (SoyPLUS; SP), or urea (UR). Ground (1
      mm) substrates were incubated in buffered rumen fluid for 24 h, and IVDMD and
      fermentation gas production kinetics and products were measured. Nitrogen
      supplementation increased (P < 0.10) ruminally fermentable fractions, IVDMD, pH,
      and concentrations of NH3 and total VFA, but reduced the rate of gas production
      (P < 0.10) and the lag phase (P < 0.01). Supplementation with UR vs. the soy
      based supplements increased ruminally fermentable fractions (P < 0.05) and
      concentrations of total VFA (P < 0.10) and NH3 (P < 0.01), but these measures
      were similar (P > 0.10) between SBM and SP. In Exp. 2, 4 steers (254 kg) were fed
      bahiagrass hay plus DCP, or hay plus DCP supplemented with CP predominantly from
      UR, SBM, or SP in a 4 x 4 Latin square design, with four 21-d periods, each with
      7 d for DMI and fecal output measurement. Nitrogen-supplemented diets were
      formulated to be isonitrogenous (11.9% CP), and all diets were formulated to be
      isocaloric (66% TDN). Intake and digestibility of DM, N, and ADF were improved (P
      < 0.05) by N supplementation. Compared with UR, the soy-based supplements led to
      greater (P < 0.05) DM and N intakes and apparent N and ADF digestibilities.
      Plasma glucose and urea concentrations increased (P < 0.10) with N
      supplementation and were greater (P < 0.01) for the soy-based supplements than
      for UR. Intake, digestibility, and plasma metabolite concentrations were similar
      (P > 0.1) for SBM and SP. In Exp. 3, 24 steers (261 kg) were individually fed
      bahiagrass hay plus DCP (control), or hay plus DCP supplemented with CP
      predominantly from UR or SBM. Over 56 d, DMI and ADG were greatest (P < 0.05) in
      steers fed SBM. Nitrogen supplementation increased (P < 0.05) DMI, ADG, and G:F.
      However, SBM supplementation produced greater (P < 0.05) DMI and ADG and similar
      (P > 0.05) G:F compared with UR supplementation. We conclude that supplemental N
      is important to optimize ruminal function and performance of growing steers fed
      forage diets supplemented with DCP. Diets with supplemental N mainly from SBM
      improved diet digestibility and animal performance beyond that achieved by UR.

PMID- 17526671
TI  - Hemodynamic responses of the caudal artery to toxic tall fescue in beef heifers.
AB  - Color Doppler ultrasonography was used to compare blood flow characteristics in
      the caudal artery of heifers fed diets with endophyte (Neotyphodium coenophialum)
      infected (E+) or noninfected (E-) tall fescue seed. Eighteen crossbred (Angus x
      Brangus) heifers were assigned to 6 pens and were fed chopped alfalfa hay for 5 d
      and chopped alfalfa hay plus a concentrate that contained E-tall fescue seed for
      9 d during an adjustment period. An 11-d experimental period followed, with
      animals in 3 pens fed chopped alfalfa hay plus a concentrate with E+ seed and
      those in the other 3 pens fed chopped hay plus concentrate with E E- seed. Color
      Doppler ultrasound measurements (caudal artery area, peak systolic velocity, end
      diastolic velocity, mean velocity, heart rate, stroke volume, and flow rate) and
      serum prolactin were monitored during the adjustment (baseline measures) and
      during the experimental period. Three baseline measures were collected on d 3, 5,
      and 6 during the adjustment period for comparison to post E+ seed exposure.
      Statistical analyses compared the proportionate differences between baseline and
      response at 4, 28, 52, 76, 100, 172, and 268 h from initial feeding of E+ seed.
      Serum prolactin concentrations on both diets were lower (P <0.001) than baseline
      beginning at 4 h from the start of the experimental period. However, trends in
      serum prolactin concentrations for heifers on the E- diet suggested ambient
      temperature was affecting these concentrations. Caudal artery area in E+ heifers
      had declined (P <0.10) from baseline by 4 h and was consistently lower (P <0.05)
      for the remainder of the period. Heart rates for E+ heifers were lower than the
      baseline rate from 4 (P <0.10) to 100 (P <0.001) h, but were similar (P >0.10) to
      the baseline for 172 and 268 h measures. Blood flow in E+ heifers was
      consistently lower than the baseline from 4 (P <0.05) to 172 (P <0.001) h, but
      was similar to the baseline at 268 h when heart rate was similar to the baseline
      rate. Caudal artery areas for the E- diet were similar to baseline areas except
      at 100 h when it was greater than baseline. Heart rates and flow rates for E-
      heifers did not differ (P >0.10) from baseline measures during the experimental
      period. Results indicated that onset of toxicosis was within 4 h of cattle
      exposure to E+ tall fescue and is related to vasoconstriction and reduction in
      heart rate.

PMID- 17526672
TI  - Effects of source of supplemental zinc on performance and humoral immunity in
      beef heifers.
AB  - Two experiments were conducted to evaluate receiving-period performance,
      morbidity, and humoral immune response, as well as finishing performance and
      carcass characteristics of heifers fed different sources of supplemental Zn. In
      Exp. 1, 97 crossbred beef heifers (initial BW = 223.4 kg) were fed a 65%
      concentrate diet with no supplemental Zn (control) or 75 mg of supplemental Zn/kg
      of DM from Zn sulfate, Zn methionine, or Zn propionate. During a 35-d receiving
      period, heifers were monitored daily for signs of bovine respiratory disease.
      Serum samples were collected for Zn analysis on d 0, 14, and 28. After the
      receiving period, heifers were adapted to and fed a high-concentrate diet with no
      supplemental Zn for 42 d. Heifers were then assigned to finishing diet
      treatments, with the same concentrations and sources of supplemental Zn as during
      the receiving period and fed for an average of 168 d. Serum samples also were
      obtained on d 0 and 56 of the finishing period and at the end of the study.
      During the receiving period, control heifers had a greater (P < or = 0.05) BW and
      G:F on d 35 than heifers in the other treatments, but no differences were
      observed among treatments for morbidity or serum Zn concentrations (P > or =
      0.50). For the finishing period, DMI and ADG did not differ among treatments;
      however, overall G:F tended (P = 0.06) to be less for control heifers than for
      heifers in the 3 supplemental Zn treatments. On d 56 of the finishing period,
      control heifers tended (P = 0.06) to have a lower serum Zn concentration than
      heifers in the 3 supplemental Zn treatments. In Exp. 2, 24 crossbred beef heifers
      (initial BW = 291.1 kg) were fed the same 4 treatments as in Exp. 1 for a 21-d
      period. The humoral immune response to treatments was determined by measuring
      specific antibody titers after s.c. injection of ovalbumin on d 0 and 14. Body
      weights and blood samples for serum Zn concentration and ovalbumin IgG titers
      were collected on d 0, 7, 14, and 21. Serum Zn concentration and specific
      ovalbumin IgG titers did not differ (P > 0.10) among the 4 treatments on any
      sampling day. Results from these 2 studies showed no major differences among the
      sources of supplemental Zn for receiving period morbidity, ADG, DMI, and humoral
      immune response of beef heifers; however, a lack of supplemental Zn during an
      extended finishing period tended to negatively affect G:F.

PMID- 17526673
TI  - Beef longissimus slice shear force measurement among steak locations and
      institutions.
AB  - The objectives of this study were 1) to determine which longissimus thoracis et
      lumborum steaks were appropriate for slice shear force measurement and 2) to
      determine the among and within institution variation in LM slice shear force
      values of 6 institutions after they received expert training on the procedure and
      a standard kit of equipment. In experiment 1, longissimus thoracis et lumborum
      muscles were obtained from the left sides of 50 US Select carcasses. Thirteen
      longissimus thoracis and 12 longissimus lumborum steaks were cut 2.54 cm thick
      from each muscle. Slice shear force was measured on each steak. Mean slice shear
      force among steak locations (1 to 25) ranged from 19.7 to 27.3 kg. Repeatability
      of slice shear force (based on variance) among steak locations ranged from 0.71
      to 0.96. In experiment 2, the longissimus thoracis et lumborum were obtained from
      the left sides of 154 US Select beef carcasses. Eight 2.54-cm-thick steaks were
      obtained from the caudal end of each frozen longissimus thoracis, and six 2.54-cm
      thick steaks were obtained from the cranial end of each frozen longissimus
      lumborum. Seven pairs of consecutive steaks were assigned for measurement of
      slice shear force. Seven institutions were assigned to steak pairs within each
      carcass using a randomized complete block design, such that each institution was
      assigned to each steak pair 22 times. Repeatability estimates for slice shear
      force for the 7 institutions were 0.89, 0.83, 0.91, 0.90, 0.89, 0.76, and 0.89,
      respectively, for institutions 1 to 7. Mean slice shear force values were least
      (P <0.05) for institutions 3 (22.7 kg) and 7 (22.3 kg) and were greatest (P
      <0.05) for institutions 5 (27.3 kg) and 6 (27.6 kg). Institutions with greater
      mean slice shear force (institutions 5 and 6) used cooking methods that required
      more (P <0.05) time (32.0 and 36.9 min vs. 5.5 to 11.8 min) to reach the end
      point temperature (71 degrees C) and resulted in greater (P <0.05) cooking loss
      (both 26.6% vs. 14.4 to 24.1%). Differences among institutions in the
      repeatability of slice shear force were partially attributable to differences
      among institutions in the consistency of steak thawing and cooking procedures.
      These results emphasize the importance of sample location within the muscle and
      cooking method in the measurement of tenderness and indicate that with proper
      training and application of the protocol, slice shear force is a highly
      repeatable (R approximately 0.90) measure of beef LM tenderness.

PMID- 17526674
TI  - Estimation of genetic parameters for body weight of the Goettingen minipig with
      random regression models.
AB  - The Goettingen minipig is a laboratory animal especially developed for medical
      research. For easy and comfortable handling during experiments, and to minimize
      costs, a low BW is essential. To breed for an even smaller minipig, genetic
      parameters for BW were estimated using a random regression model (RRM). The RRM
      was calculated using random animal, common litter environment, and permanent
      environment effects, respectively. Regressions for the random effects in the RRM
      were modeled using Legendre polynomials from second to fourth order of fit in
      different combinations. The model was applied to a data set that focused on the
      time period from 30 to 400 d of age. Eight age classes were built to consider
      heterogeneous residual variances. The heritabilities were moderate and ranged
      from 0.211 (375 d of age) to 0.254 (275 d of age). The variances initially
      decreased and then increased toward the end of the examined time period for
      permanent environment and litter effects. Genetic and phenotypic correlations
      between BW in different age classes decreased with increasing distance between
      age classes. The major eigenfunction showed positive values throughout the whole
      trajectory (i.e., a selection for low BW had positive effects on this trait
      throughout the whole range of time). On the basis of the estimated genetic
      parameters, a breeding scheme can be created to develop genetically smaller
      Goettingen minipigs in the future.

PMID- 17526675
TI  - Muscle fibre type shifting in the vastus lateralis of patients with COPD is
      associated with disease severity: a systematic review and meta-analysis.
AB  - BACKGROUND: Skeletal muscle dysfunction is a common feature in chronic
      obstructive pulmonary disease (COPD) which is associated with intrinsic muscular
      abnormalities. One of the most consistently reported alterations is a shift from
      fibre type I to II in the vastus lateralis of these patients. Surprisingly, the
      relationship between this shift and the severity and phenotype of COPD remains
      unclear. A study was conducted to determine whether vastus lateralis muscle fibre
      type proportions are associated with COPD disease severity and to provide
      reference values for the proportions of fibre types in the vastus lateralis in
      COPD. METHODS: A systematic review and a meta-analysis were conducted in which
      muscle fibre type data and markers of disease severity were collected from the
      literature. RESULTS: The forced expiratory volume in 1 s (FEV(1)), the ratio of
      FEV(1) to forced vital capacity (FVC) and body mass index were positively
      associated with the proportion of type I fibres in COPD. A proportion of 51% for
      vastus lateralis fibre type I and 13% for fibre type IIX were calculated from the
      combined data as normal values for patients with typical GOLD stage 3-4 COPD aged
      60-70 years. Based on these reference values, a proportion of fibre type I <27%
      and of fibre type IIX >29% were defined as pathologically abnormal. CONCLUSIONS:
      This review sheds new light on the relationship between skeletal muscle
      abnormalities and important hallmarks of the disease in severe COPD, and
      identifies absence of data in GOLD stages 1-2. This review also provides
      reference values on fibre type composition for diagnostic purposes in COPD.

PMID- 17526676
TI  - Airway remodelling in children with cystic fibrosis.
AB  - BACKGROUND: The relationship between airway structural changes and inflammation
      is unclear in early cystic fibrosis (CF) lung disease. A study was undertaken to
      determine changes in airway remodelling in children with CF compared with
      appropriate disease and healthy controls. METHODS: Bronchoalveolar lavage and
      endobronchial biopsy were performed in a cross-sectional study of 43 children
      with CF (aged 0.3-16.8 years), 7 children with primary ciliary dyskinesia (PCD),
      26 with chronic respiratory symptoms (CRS) investigated for recurrent infection
      and/or cough and 7 control children with no lower airway symptoms. Inflammatory
      cells, cytokines, proteases and matrix constituents were measured in
      bronchoalveolar lavage fluid (BALF). Reticular basement membrane (RBM) thickness
      was measured on biopsy specimens using light microscopy. RESULTS: Increased
      concentrations of elastin, glycosaminoglycans and collagen were found in BALF
      from children with CF compared with the CRS group and controls, each correlating
      positively with age, neutrophil count and proteases (elastase activity and matrix
      metalloproteinase-9 (MMP-9) concentration). There were significant negative
      correlations between certain of these and pulmonary function (forced expiratory
      volume in 1 s) in the CF group (elastin: r = -0.45, p<0.05; MMP-9:TIMP-1 ratio: r
      = -0.47, p<0.05). Median RBM thickness was greater in the CF group than in the
      controls (5.9 microm vs 4.0 microm, p<0.01) and correlated positively with levels
      of transforming growth factor-beta(1) (TGF-beta(1); r = 0.53, p = 0.01), although
      not with other inflammatory markers or pulmonary function. CONCLUSIONS: This
      study provides evidence for two forms of airway remodelling in children with CF:
      (1) matrix breakdown, related to inflammation, proteolysis and impaired pulmonary
      function, and (2) RBM thickening, related to TGF-beta(1) concentration but
      independent of other markers of inflammation.

PMID- 17526677
TI  - Reactivation of tuberculosis and vitamin D deficiency: the contribution of diet
      and exposure to sunlight.
AB  - BACKGROUND: As well as its role in the regulation of calcium metabolism, vitamin
      D is an immunoregulatory hormone. Epidemiological evidence also suggests a link
      between vitamin D deficiency and tuberculosis (TB). A study was undertaken to
      examine serum vitamin D concentrations before treatment in patients with active
      TB and their contacts from the same ethnic and social background and to
      investigate the relative contributions of diet and sunlight exposure. METHODS:
      Serum vitamin D concentrations were measured before treatment in 178 patients
      with active TB and 130 healthy contacts. The prevalence of vitamin D deficiency
      and its relation to skin colour, month of estimation and TB diagnosis were
      determined. 35 patients and 35 frequency-matched contacts completed dietary and
      sun exposure questionnaires to determine the relative contribution of these to
      serum vitamin D concentrations. RESULTS: There was a statistically significant
      difference in serum vitamin D concentrations between patients and contacts (20.1
      vs 30.8 nmol/l, 95% CI 7.1 to 14.3; p<0.001) and significantly more patients had
      severely deficient concentrations (<21 nmol/l) than controls (114/178 (64%) vs
      40/130 (31%), p<0.001). There was no association between serum concentrations of
      vitamin D and skin pigmentation. The healthy contacts showed a predictable
      seasonal pattern, rising to peak concentrations in the summer months, but this
      response was absent in patients with TB. Dietary intake was the same in both
      patients with TB and contacts matched for age, sex and skin colour, but patients
      with TB displayed a stronger correlation between serum vitamin D concentrations
      and dietary intake (r = 0.42, p = 0.016) than controls (r = 0.13, p>0.1). There
      was no difference in sunlight exposure between the groups. CONCLUSIONS: Patients
      with active TB have lower serum vitamin D concentrations than contacts from
      similar ethnic and social backgrounds and with comparable dietary intake and sun
      exposure, and do not show the expected seasonal variation. These observations
      indicate that other factors are contributing to vitamin D deficiency in patients
      with TB and suggest abnormal handling of this vitamin.

PMID- 17526678
TI  - Scientific freedom.

PMID- 17526679
TI  - Physicians' intent to comply with the American Medical Association's guidelines
      on gifts from the pharmaceutical industry.
AB  - OBJECTIVE: To identify factors that predict physicians' intent to comply with the
      American Medical Association's (AMA's) ethical guidelines on gifts from the
      pharmaceutical industry. METHODS: A survey was designed and mailed in June 2004
      to a random sample of 850 physicians in Florida, USA, excluding physicians with
      inactive licences, incomplete addresses, addresses in other states and pretest
      participants. Factor analysis extracted six factors: attitude towards following
      the guidelines, subjective norms (eg, peers, patients, etc), facilitating
      conditions (eg, knowledge of the guidelines, etc), profession-specific precedents
      (eg, institution's policies, etc), individual-specific precedents (physicians'
      own discretion, policies, etc) and intent. Multivariate regression modelling was
      conducted. RESULTS: Surveys were received from 213 physicians representing all
      specialties, with a net response rate of 25.5%. 62% (n = 133) of respondents were
      aware of the guidelines; 50% (n = 107) had read them. 48% (n = 102) thought that
      following the guidelines would increase physicians' credibility and professional
      image; 68% (n = 145) agreed that it was important to do so. Intent to comply was
      positively associated with attitude, subjective norms, facilitators and
      sponsorship of continuing medical education (CME) events, while individual
      specific precedents had a negative relationship with intent to comply. Predictors
      of intent (R(2) = 0.52, p <0) were attitude, subjective norms, the interaction
      term (attitude and subjective norms), sponsorship of CME events and individual
      specific precedents. CONCLUSIONS: Physicians are more likely to follow the AMA
      guidelines if they have positive attitudes towards the guidelines, greater
      subjective norms, fewer expectations of CME sponsorship and fewer individual
      specific precedents. Physicians believing that important individuals or
      organisations expect them to comply with the guidelines are more likely to
      express intent, despite having fewer beliefs that positive outcomes would result
      through compliance.

PMID- 17526680
TI  - Views regarding the training of ethics consultants: a survey of physicians caring
      for patients in ICU.
AB  - BACKGROUND: Despite the expansion of ethics consultation services, questions
      remain about the aims of clinical ethics consultation, its methods and the
      expertise of those who provide such services. OBJECTIVE: To describe physicians'
      expectations regarding the training and skills necessary for ethics consultants
      to contribute effectively to the care of patients in intensive care unit (ICU).
      DESIGN: Mailed survey. PARTICIPANTS: Physicians responsible for the care of at
      least 10 patients in ICU over a 6-month period at a 921-bed private teaching
      hospital with an established ethics consultation service. 69 of 92 (75%) eligible
      physicians responded. MEASUREMENTS: Importance of specialised knowledge and
      skills for ethics consultants contributing to the care of patients in ICU; need
      for advanced disciplinary training; expectations regarding formal-training
      programmes for ethics consultants. RESULTS: Expertise in ethics was described
      most often as important for ethics consultants taking part in the care of
      patients in ICU, compared with expertise in law (p<0.03), religious traditions
      (p<0.001), medicine (p<0.001) and conflict-mediation techniques (p<0.001). When
      asked about the formal training consultants should possess, however, physicians
      involved in the care of patients in ICU most often identified advanced medical
      training as important. CONCLUSIONS: Although many physicians caring for patients
      in ICU believe ethics consultants must possess non-medical expertise in ethics
      and law if they are to contribute effectively to patient care, these physicians
      place a very high value on medical training as well, suggesting a "medicine plus
      one" view of the training of an ideal ethics consultant. As ethics consultation
      services expand, clear expectations regarding the training of ethics consultants
      should be established.

PMID- 17526681
TI  - Placebos: the nurse and the iron pills.
AB  - In sub-Saharan Africa, a nurse gives iron pills as placebos to terminally ill
      patients. She tells them, acting in what she believes is in their best interests,
      "these will make you feel better". The patients believe it will help their AIDS
      and their well-being improves. Do the motive and the patient's positive outcome
      in well-being make the deceit justifiable when other issues such as consent,
      autonomy and potential consequences regarding the patient and the wider community
      are considered? Is there a difference between lying and non-lying deception when
      the end result is the same? The patients feel better, but at what cost if the
      deceit was found out? It will be argued that although the actions of the nurse
      are understandable and to some extent defensible, they are unethical. It is not
      ethically acceptable to take away the patient's autonomy and risk the health of
      the community even though the risk of deceit being discovered is a small one.

PMID- 17526682
TI  - Routine antenatal HIV testing: the responses and perceptions of pregnant women
      and the viability of informed consent. A qualitative study.
AB  - This qualitative cross-sectional survey, undertaken in the antenatal booking
      clinics of a hospital in central London, explores pregnant women's responses to
      routine HIV testing, examines their reasons for declining or accepting the test,
      and assesses how far their responses fulfil standard criteria for informed
      consent. Of the 32 women interviewed, only 10 participants were prepared for HIV
      testing at their booking interview. None of the women viewed themselves as being
      particularly at risk for HIV infection. The minority (n = 6) of the participants
      who declined testing differed from those who accepted, by interpreting test
      acceptance as risky behaviour, privileging the negative outcomes of HIV
      positivity and expressing an inability to cope with these, should they occur.
      Troublingly, only a minority of women (n = 9) had a broad understanding of the
      rationale for the test, and none fulfilled the standard criteria for informed
      consent. This study suggests that, although routine screening combined with
      professional recommendation may be successful in increasing uptake, this may be
      at the cost of eroding informed consent. Protecting third parties (notably
      fetuses) from a preventable disease may outweigh the moral duty of respecting
      autonomy, enshrined in Western bioethical tradition. Nevertheless, such a policy
      should be made transparent, debated in the public domain and negotiated with
      women seeking antenatal care.

PMID- 17526683
TI  - Ethical dilemmas in forensic psychiatry: two illustrative cases.
AB  - One approach to the analysis of ethical dilemmas in medical practice uses the
      "four principles plus scope" approach. These principles are: respect for
      autonomy, beneficence, non-maleficence and justice, along with concern for their
      scope of application. However, conflicts between the different principles are
      commonplace in psychiatric practice, especially in forensic psychiatry, where
      duties to patients often conflict with duties to third parties such as the
      public. This article seeks to highlight some of the specific ethical dilemmas
      encountered in forensic psychiatry: the excessive use of segregation for the
      protection of others, the ethics of using mechanical restraint when clinically
      beneficial and the use of physical treatment without consent. We argue that
      justice, as a principle, should be paramount in forensic psychiatry, and that
      there is a need for a more specific code of ethics to cover specialised areas of
      medicine like forensic psychiatry. This code should specify that in cases of
      conflict between different principles, justice should gain precedence over the
      other principles.

PMID- 17526684
TI  - What constitutional protection for freedom of scientific research?

PMID- 17526685
TI  - Is cell science dangerous?

PMID- 17526686
TI  - Scientists, bioethics and democracy: the Italian case and its meanings.
AB  - In June 2005, Italy held a referendum on repealing the law on medically assisted
      fertilization (Law 40/2004), which limits access to artificial reproduction to
      infertile couples, and prohibits the donation of gametes, the cryopreservation of
      embryos, preimplantation genetic diagnosis (PDG), and research on human embryos.
      The referendum was invalidated, and the law remained unchanged. The Italian
      political e bioethical debate on assisted reproduction was manipulated by the
      Catholic Church, which distorted scientific data and issues at stake with the
      help of Catholic politicians and bioethicists. What happened in Italy shows that
      some perverse socio-cultural e political mechanisms are spreading the absurd and
      anti-historical view that scientific and technological advancements are
      threatening democracy and personal freedom. Scientists should not only contrast
      the political attempts at limiting freedom of scientific research, but also tell
      politicians, humanists and citizens that the invention of Western science with
      its view of scientific community as an "open society", contributed and still
      contributes, through scientific education, to the construction and maintaining of
      the moral and political values underlying Western democracies.

PMID- 17526687
TI  - Is respect for autonomy defensible?
AB  - Three main claims are made in this paper. First, it is argued that Onora O'Neill
      has uncovered a serious problem in the way medical ethicists have thought about
      both respect for autonomy and informed consent. Medical ethicists have tended to
      think that autonomous choices are intrinsically worthy of respect, and that
      informed consent procedures are the best way to respect the autonomous choices of
      individuals. However, O'Neill convincingly argues that we should abandon both
      these thoughts. Second, it is argued that O'Neill's proposed solution to this
      problem is inadequate. O'Neill's approach requires that a more modest view of the
      purpose of informed consent procedures be adopted. In her view, the purpose of
      informed consent procedures is simply to avoid deception and coercion, and the
      ethical justification for informed consent derives from a different ethical
      principle, which she calls principled autonomy. It is argued that contrary to
      what O'Neill claims, the wrongness of coercion cannot be derived from principled
      autonomy, and so its credentials as a justification for informed consent
      procedures is weak. Third, it is argued that we do better to rethink autonomy and
      informed consent in terms of respecting persons as ends in themselves, and a
      characteristically liberal commitment to allowing individuals to make certain
      categories of decisions for themselves.

PMID- 17526688
TI  - Male circumcision and HIV prevention: ethical, medical and public health
      tradeoffs in low-income countries.

PMID- 17526689
TI  - Legal and institutional fictions in medical ethics: a common, and yet largely
      overlooked, phenomenon.

PMID- 17526690
TI  - Scientific misconduct from the perspective of research coordinators: a national
      survey.
AB  - OBJECTIVE: To report results from a national survey of coordinators and managers
      of clinical research studies in the US on their perceptions of and experiences
      with scientific misconduct. METHODS: Data were collected using the Scientific
      Misconduct Questionnaire-Revised. Eligible responses were received from 1645 of
      5302 (31%) surveys sent to members of the Association of Clinical Research
      Professionals and to subscribers of Research Practitioner, published by the
      Center for Clinical Research Practice, between February 2004 and January 2005.
      FINDINGS: Overall, the perceived frequency of misconduct was low. Differences
      were noted between workplaces with regard to perceived pressures on investigators
      and research coordinators, and on the effectiveness of the regulatory environment
      in reducing misconduct. First-hand experience with an incident of misconduct was
      reported by 18% of respondents. Those with first-hand knowledge of misconduct
      were more likely to report working in an academic medical setting, and to report
      that a typical research coordinator would probably do nothing if aware that a
      principal investigator or research staff member was involved in an incident of
      misconduct. CONCLUSION: These findings expand the knowledge on scientific
      misconduct by adding new information from the perspective of research
      coordinators. The findings provide some data supporting the influence of
      workplace climate on misconduct and also on the perceived effectiveness of
      institutional policies to reduce scientific misconduct.

PMID- 17526691
TI  - Moral theories in teaching applied ethics.
AB  - It is argued, in this paper, that moral theories should not be discussed
      extensively when teaching applied ethics. First, it is argued that, students are
      either presented with a large amount of information regarding the various subtle
      distinctions and the nuances of the theory and, as a result, the students simply
      fail to take it in or, alternatively, the students are presented with a
      simplified caricature of the theory, in which case the students may understand
      the information they are given, but what they have understood is of little or no
      value because it is merely a caricature of a theory. Second, there is a
      methodological problem with appealing to moral theories to solve particular
      issues in applied ethics. An analogy with science is appealed to. In physics
      there is a hope that we could discover a unified theory of everything. But this
      is, of course, a hugely ambitious project, and much harder than, for example,
      finding a theory of motion. If the physicist wants to understand motion, he
      should try to do so directly. We would think he was particularly misguided if he
      thought that, to answer this question, he first needed to construct a unified
      theory of everything.

PMID- 17526692
TI  - CsrA inhibits translation initiation of Escherichia coli hfq by binding to a
      single site overlapping the Shine-Dalgarno sequence.
AB  - Csr (carbon storage regulation) of Escherichia coli is a global regulatory system
      that consists of CsrA, a homodimeric RNA binding protein, two noncoding small
      RNAs (sRNAs; CsrB and CsrC) that function as CsrA antagonists by sequestering
      this protein, and CsrD, a specificity factor that targets CsrB and CsrC for
      degradation by RNase E. CsrA inhibits translation initiation of glgC, cstA, and
      pgaA by binding to their leader transcripts and preventing ribosome binding.
      Translation inhibition is thought to contribute to the observed mRNA
      destabilization. Each of the previously known target transcripts contains
      multiple CsrA binding sites. A position-specific weight matrix search program was
      developed using known CsrA binding sites in mRNA. This search tool identified a
      potential CsrA binding site that overlaps the Shine-Dalgarno sequence of hfq, a
      gene that encodes an RNA chaperone that mediates sRNA-mRNA interactions. This
      putative CsrA binding site matched the SELEX-derived binding site consensus
      sequence in 8 out of 12 positions. Results from gel mobility shift and footprint
      assays demonstrated that CsrA binds specifically to this site in the hfq leader
      transcript. Toeprint and cell-free translation results indicated that bound CsrA
      inhibits Hfq synthesis by competitively blocking ribosome binding. Disruption of
      csrA caused elevated expression of an hfq'-'lacZ translational fusion, while
      overexpression of csrA inhibited expression of this fusion. We also found that
      hfq mRNA is stabilized upon entry into stationary-phase growth by a CsrA
      independent mechanism. The interaction of CsrA with hfq mRNA is the first example
      of a CsrA-regulated gene that contains only one CsrA binding site.

PMID- 17526693
TI  - The pneumococcal two-component signal transduction system RR/HK06 regulates CbpA
      and PspA by two distinct mechanisms.
AB  - We have previously shown that CbpA, a major pneumococcal virulence factor, is
      regulated by the two-component signal transduction system RR/HK06 (A. J.
      Standish, U. H. Stroeher, and J. C. Paton, Proc. Natl. Acad. Sci. USA 102:7701
      7706, 2005). However, additional unidentified regulated factors appeared to be
      responsible for differences in adherence and the ability of Streptococcus
      pneumoniae to cause disease in a mouse model. Here, we identified a number of
      other regulated genes by overexpressing the system. cbpA, along with a
      cotranscribed upstream gene, showed substantial increases in expression when RR06
      was overexpressed in S. pneumoniae strains D39 and TIGR4. However, there were no
      other similarities between these strains. In D39, rr06 overexpression decreased
      expression of numerous factors, including the major virulence factor gene pspA.
      Further investigation of cbpA regulation by RR/HK06, using mutants with mutations
      in both HK06 and RR06, suggested that rather than the norm, cbpA transcription
      was activated when RR06 was in the nonphosphorylated form. Although other
      factors, such as pspA and gls24, are regulated by this system, these genes appear
      to be repressed when RR06 is in its phosphorylated form.

PMID- 17526694
TI  - Functional characterization of the Sinorhizobium meliloti acetate metabolism
      genes aceA, SMc00767, and glcB.
AB  - The genes encoding malate synthase (glcB) and isocitrate lyase (aceA) and a 240
      bp open reading frame (SMc00767) located downstream of aceA were isolated and
      functionally characterized in Sinorhizobium meliloti. Independent and double
      interposon mutants of each gene were constructed, and the corresponding
      phenotypes were analyzed. aceA mutants failed to grow on acetate, and mutants
      deficient in SMc00767 were also affected in acetate utilization. In contrast,
      mutants deficient in glcB grew on acetate similar to wild-type strain Rm5000.
      Complementation experiments showed that aceA and SMc00767 gene constructs were
      able to restore the growth on acetate in the corresponding single mutants. aceA
      glcB, aceA-SMc00767, and glcB-SMc00767 double knockouts were also unable to grow
      on acetate, but this ability was recovered when the wild-type aceA-glcB or aceA
      SMc00767 loci were introduced into the double mutants. These data confirm the
      functional role of aceA and SMc00767 and show that glcB, in the absence of
      SMc00767, is required for acetate metabolism. Isocitrate lyase and malate
      synthase activities were measured in strain Rm5000, the mutant derivatives, and
      complemented strains. aceA and glcB were able to complement the enzymatic
      activity lacking in the corresponding single mutants. The enzymatic activities
      also showed that SMc00767 represses the activity of isocitrate lyase in cells
      grown on acetate. Gene fusions confirmed the repressor role of SMc00767, which
      regulates aceA expression at the transcriptional level. Comparison of the
      transcriptional profiles of the SMc00767 mutant and wild-type strain Rm5000
      showed that SMc00767 represses the expression of a moderate number of open
      reading frames, including aceA; thus, we propose that SMc00767 is a novel
      repressor involved in acetate metabolism in S. meliloti. Genetic and functional
      analyses indicated that aceA and SMc00767 constitute a functional two-gene
      operon, which is conserved in other alpha-proteobacteria. Alfalfa plants infected
      with the aceA and glcB mutants were not impaired in nodulation or nitrogen
      fixation, and so the glyoxylate cycle is not required in the Rhizobium-legume
      symbiosis.

PMID- 17526695
TI  - Inactivation of the DnaB helicase leads to the collapse and degradation of the
      replication fork: a comparison to UV-induced arrest.
AB  - Replication forks face a variety of structurally diverse impediments that can
      prevent them from completing their task. The mechanism by which cells overcome
      these hurdles is likely to vary depending on the nature of the obstacle and the
      strand in which the impediment is encountered. Both UV-induced DNA damage and
      thermosensitive replication proteins have been used in model systems to inhibit
      DNA replication and characterize the mechanism by which it recovers. In this
      study, we examined the molecular events that occur at replication forks following
      inactivation of a thermosensitive DnaB helicase and found that they are distinct
      from those that occur following arrest at UV-induced DNA damage. Following UV
      induced DNA damage, the integrity of replication forks is maintained and
      protected from extensive degradation by RecA, RecF, RecO, and RecR until
      replication can resume. By contrast, inactivation of DnaB results in extensive
      degradation of the nascent and leading-strand template DNA and a loss of
      replication fork integrity as monitored by two-dimensional agarose gel analysis.
      The degradation that occurs following DnaB inactivation partially depends on
      several genes, including recF, recO, recR, recJ, recG, and xonA. Furthermore, the
      thermosensitive DnaB allele prevents UV-induced DNA degradation from occurring
      following arrest even at the permissive temperature, suggesting a role for DnaB
      prior to loading of the RecFOR proteins. We discuss these observations in
      relation to potential models for both UV-induced and DnaB(Ts)-mediated
      replication inhibition.

PMID- 17526696
TI  - Thermoregulation of Escherichia coli hchA transcript stability.
AB  - The conserved chaperone Hsp31 of Escherichia coli is transcribed at low
      temperatures by sigma(S) and repressed by H-NS, whereas at high temperature,
      transcription is by sigma70 independently of both sigma(S) and H-NS. Here we
      present evidence for an additional, novel, temperature-dependent control of Hsp31
      expression by increased transcript stability.

PMID- 17526697
TI  - Characterization of biphenyl dioxygenase of Pandoraea pnomenusa B-356 as a potent
      polychlorinated biphenyl-degrading enzyme.
AB  - Biphenyl dioxygenase (BPDO) catalyzes the aerobic transformation of biphenyl and
      various polychlorinated biphenyls (PCBs). In three different assays, BPDO(B356)
      from Pandoraea pnomenusa B-356 was a more potent PCB-degrading enzyme than
      BPDO(LB400) from Burkholderia xenovorans LB400 (75% amino acid sequence
      identity), transforming nine congeners in the following order of preference:
      2,3',4-trichloro approximately 2,3,4'-trichloro > 3,3'-dichloro > 2,4,4'
      trichloro > 4,4'-dichloro approximately 2,2'-dichloro > 2,6-dichloro > 2,2',3,3'
      tetrachloro approximately 2,2',5,5'-tetrachloro. Except for 2,2',5,5'
      tetrachlorobiphenyl, BPDO(B356) transformed each congener at a higher rate than
      BPDO(LB400). The assays used either whole cells or purified enzymes and either
      individual congeners or mixtures of congeners. Product analyses established
      previously unrecognized BPDO(B356) activities, including the 3,4-dihydroxylation
      of 2,6-dichlorobiphenyl. BPDO(LB400) had a greater apparent specificity for
      biphenyl than BPDO(B356) (k(cat)/K(m) = 2.4 x 10(6) +/- 0.7 x 10(6) M(-1) s(-1)
      versus k(cat)/K(m) = 0.21 x 10(6) +/- 0.04 x 10(6) M(-1) s(-1)). However, the
      latter transformed biphenyl at a higher maximal rate (k(cat) = 4.1 +/- 0.2 s(-1)
      versus k(cat) = 0.4 +/- 0.1 s(-1)). A variant of BPDO(LB400) containing four
      active site residues of BPDO(B356) transformed para-substituted congeners better
      than BPDO(LB400). Interestingly, a substitution remote from the active site,
      A267S, increased the enzyme's preference for meta-substituted congeners.
      Moreover, this substitution had a greater effect on the kinetics of biphenyl
      utilization than substitutions in the substrate-binding pocket. In all variants,
      the degree of coupling between congener depletion and O(2) consumption was
      approximately proportional to congener depletion. At 2.4-A resolution, the
      crystal structure of the BPDO(B356)-2,6-dichlorobiphenyl complex, the first
      crystal structure of a BPDO-PCB complex, provided additional insight into the
      reactivity of this isozyme with this congener, as well as into the differences in
      congener preferences of the BPDOs.

PMID- 17526698
TI  - Gene cloning and characterization of the very large NAD-dependent l-glutamate
      dehydrogenase from the psychrophile Janthinobacterium lividum, isolated from cold
      soil.
AB  - NAD-dependent l-glutamate dehydrogenase (NAD-GDH) activity was detected in cell
      extract from the psychrophile Janthinobacterium lividum UTB1302, which was
      isolated from cold soil and purified to homogeneity. The native enzyme (1,065
      kDa, determined by gel filtration) is a homohexamer composed of 170-kDa subunits
      (determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis).
      Consistent with these findings, gene cloning and sequencing enabled deduction of
      the amino acid sequence of the subunit, which proved to be comprised of 1,575
      amino acids with a combined molecular mass of 169,360 Da. The enzyme from this
      psychrophile thus appears to belong to the GDH family characterized by very large
      subunits, like those expressed by Streptomyces clavuligerus and Pseudomonas
      aeruginosa (about 180 kDa). The entire amino acid sequence of the J. lividum
      enzyme showed about 40% identity with the sequences from S. clavuligerus and P.
      aeruginosa enzymes, but the central domains showed higher homology (about 65%).
      Within the central domain, the residues related to substrate and NAD binding were
      highly conserved, suggesting that this is the enzyme's catalytic domain. In the
      presence of NAD, but not in the presence of NADP, this GDH exclusively catalyzed
      the oxidative deamination of l-glutamate. The stereospecificity of the hydride
      transfer to NAD was pro-S, which is the same as that of the other known GDHs.
      Surprisingly, NAD-GDH activity was markedly enhanced by the addition of various
      amino acids, such as l-aspartate (1,735%) and l-arginine (936%), which strongly
      suggests that the N- and/or C-terminal domains play regulatory roles and are
      involved in the activation of the enzyme by these amino acids.

PMID- 17526699
TI  - The LysR-type transcriptional regulator YofA controls cell division through the
      regulation of expression of ftsW in Bacillus subtilis.
AB  - We have carried out a functional analysis of LysR family transcriptional
      regulators in Bacillus subtilis. The cell density of cultures of a yofA insertion
      mutant declined sharply after the end of exponential growth, as measured by
      optical density at 600 nm. Complementation in trans and analysis of isopropyl
      beta-d-thiogalactopyranoside (IPTG)-dependent growth of an inducible yofA strain
      confirmed that YofA contributes to the cell density of a culture after the end of
      exponential growth. Microscopic observation suggested that cell division is
      inhibited or delayed in the yofA mutant during entry into stationary phase.
      Analysis of the transcription of cell division genes revealed that the expression
      of ftsW is inhibited in yofA mutants, and overexpression of yofA, driven by a
      multiple-copy plasmid, enhances the induction of ftsW expression. These results
      suggest that YofA is required for the final round of cell division before entry
      into stationary phase and that YofA positively regulates ftsW expression. The
      defects caused by mutation of yofA were suppressed in strains carrying P(spac)
      ftsW in the presence of IPTG. Furthermore, maximal expression of yofA was
      observed at the onset of stationary phase, which coincided with the maximal ftsW
      expression. Our data indicate that YofA is involved in cell division through
      positive regulation of the expression of ftsW in B. subtilis.

PMID- 17526700
TI  - Interactions between the lipoprotein PilP and the secretin PilQ in Neisseria
      meningitidis.
AB  - Neisseria meningitidis can be the causative agent of meningitis or septicemia.
      This bacterium expresses type IV pili, which mediate a variety of functions,
      including autoagglutination, twitching motility, biofilm formation, adherence,
      and DNA uptake during transformation. The secretin PilQ supports type IV pilus
      extrusion and retraction, but it also requires auxiliary proteins for its
      assembly and localization in the outer membrane. Here we have studied the
      physical properties of the lipoprotein PilP and examined its interaction with
      PilQ. We found that PilP was an inner membrane protein required for pilus
      expression and transformation, since pilP mutants were nonpiliated and
      noncompetent. These mutant phenotypes were restored by the expression of PilP in
      trans. The pilP gene is located upstream of pilQ, and analysis of their
      transcripts indicated that pilP and pilQ were cotranscribed. Furthermore,
      analysis of the level of PilQ expression in pilP mutants revealed greatly reduced
      amounts of PilQ only in the deletion mutant, exhibiting a polar effect on pilQ
      transcription. In vitro experiments using recombinant fragments of PilP and PilQ
      showed that the N-terminal region of PilP interacted with the middle part of the
      PilQ polypeptide. A three-dimensional reconstruction of the PilQ-PilP interacting
      complex was obtained at low resolution by transmission electron microscopy, and
      PilP was shown to localize around the cap region of the PilQ oligomer. These
      findings suggest a role for PilP in pilus biogenesis. Although PilQ does not need
      PilP for its stabilization or membrane localization, the specific interaction
      between these two proteins suggests that they might have another coordinated
      activity in pilus extrusion/retraction or related functions.

PMID- 17526701
TI  - Double-strand break generation under deoxyribonucleotide starvation in
      Escherichia coli.
AB  - Stalled replication forks produced by three different ways of depleting
      deoxynucleoside triphosphate showed different capacities to undergo "replication
      fork reversal." This reaction occurred at the stalled forks generated by
      hydroxyurea treatment, was impaired under thermal inactivation of ribonucleoside
      reductase, and did not take place under thymine starvation.

PMID- 17526702
TI  - AtlA functions as a peptidoglycan lytic transglycosylase in the Neisseria
      gonorrhoeae type IV secretion system.
AB  - Type IV secretion systems require peptidoglycan lytic transglycosylases for
      efficient secretion, but the function of these enzymes is not clear. The type IV
      secretion system gene cluster of Neisseria gonorrhoeae encodes two peptidoglycan
      transglycosylase homologues. One, LtgX, is similar to peptidoglycan
      transglycosylases from other type IV secretion systems. The other, AtlA, is
      similar to endolysins from bacteriophages and is not similar to any described
      type IV secretion component. We characterized the enzymatic function of AtlA in
      order to examine its role in the type IV secretion system. Purified AtlA was
      found to degrade macromolecular peptidoglycan and to produce 1,6-anhydro
      peptidoglycan monomers, characteristic of lytic transglycosylase activity. We
      found that AtlA can functionally replace the lambda endolysin to lyse Escherichia
      coli. In contrast, a sensitive measure of lysis demonstrated that AtlA does not
      lyse gonococci expressing it or gonococci cocultured with an AtlA-expressing
      strain. The gonococcal type IV secretion system secretes DNA during growth. A
      deletion of ltgX or a substitution in the putative active site of AtlA severely
      decreased DNA secretion. These results indicate that AtlA and LtgX are actively
      involved in type IV secretion and that AtlA is not involved in lysis of gonococci
      to release DNA. This is the first demonstration that a type IV secretion
      peptidoglycanase has lytic transglycosylase activity. These data show that AtlA
      plays a role in type IV secretion of DNA that requires peptidoglycan breakdown
      without cell lysis.

PMID- 17526703
TI  - An anhydro-N-acetylmuramyl-L-alanine amidase with broad specificity tethered to
      the outer membrane of Escherichia coli.
AB  - From its amino acid sequence homology with AmpD, we recognized YbjR, now renamed
      AmiD, as a possible second 1,6-anhydro-N-acetylmuramic acid (anhMurNAc)-l-alanine
      amidase in Escherichia coli. We have now confirmed that AmiD is an anhMurNAc-l
      Ala amidase and demonstrated that AmpD and AmiD are the only enzymes present in
      E. coli that are able to cleave the anhMurNAc-l-Ala bond. The activity was
      present only in the outer membrane fraction obtained from an ampD mutant. In
      contrast to AmpD, which is specific for the anhMurNAc-l-alanine bond, AmiD also
      cleaved the bond between MurNAc and l-alanine in both muropeptides and murein
      sacculi. Unlike the periplasmic murein amidases, AmiD did not participate in cell
      separation. ampG mutants, which are unable to import GlcNAc-anhMurNAc-peptides
      into the cytoplasm, released mainly peptides into the medium due to AmiD
      activity, whereas an ampG amiD double mutant released a large amount of intact
      GlcNAc-anhMurNAc-peptides into the medium.

PMID- 17526704
TI  - Pyocyanin alters redox homeostasis and carbon flux through central metabolic
      pathways in Pseudomonas aeruginosa PA14.
AB  - The opportunistic pathogen Pseudomonas aeruginosa produces colorful, redox-active
      antibiotics called phenazines. Excretion of pyocyanin, the best-studied natural
      phenazine, is responsible for the bluish tint of sputum and pus associated with
      P. aeruginosa infections in humans. Although the toxicity of pyocyanin for other
      bacteria, as well as its role in eukaryotic infection, has been studied
      extensively, the physiological relevance of pyocyanin metabolism for the
      producing organism is not well understood. Pyocyanin reduction by P. aeruginosa
      PA14 is readily observed in standing liquid cultures that have consumed all of
      the oxygen in the medium. We investigated the physiological consequences of
      pyocyanin reduction by assaying intracellular concentrations of NADH and NAD+ in
      the wild-type strain and a mutant defective in phenazine production. We found
      that the mutant accumulated more NADH in stationary phase than the wild type.
      This increased accumulation correlated with a decrease in oxygen availability and
      was relieved by the addition of nitrate. Pyocyanin addition to a phenazine-null
      mutant also decreased intracellular NADH levels, suggesting that pyocyanin
      reduction facilitates redox balancing in the absence of other electron acceptors.
      Analysis of extracellular organic acids revealed that pyocyanin stimulated
      stationary-phase pyruvate excretion in P. aeruginosa PA14, indicating that
      pyocyanin may also influence the intracellular redox state by decreasing carbon
      flux through central metabolic pathways.

PMID- 17526705
TI  - Crystal structure of the Vibrio cholerae quorum-sensing regulatory protein HapR.
AB  - Quorum sensing in Vibrio cholerae involves signaling between two-component sensor
      protein kinases and the response regulator LuxO to control the expression of the
      master regulator HapR. HapR, in turn, plays a central role in regulating a number
      of important processes, such as virulence gene expression and biofilm formation.
      We have determined the crystal structure of HapR to 2.2-A resolution. Its
      structure reveals a dimeric, two-domain molecule with an all-helical structure
      that is strongly conserved with members of the TetR family of transcriptional
      regulators. The N-terminal DNA-binding domain contains a helix-turn-helix DNA
      binding motif and alteration of certain residues in this domain completely
      abolishes the ability of HapR to bind to DNA, alleviating repression of both
      virulence gene expression and biofilm formation. The C-terminal dimerization
      domain contains a unique solvent accessible tunnel connected to an amphipathic
      cavity, which by analogy with other TetR regulators, may serve as a binding
      pocket for an as-yet-unidentified ligand.

PMID- 17526706
TI  - Gene expression analysis of Corynebacterium glutamicum subjected to long-term
      lactic acid adaptation.
AB  - Corynebacteria form an important part of the red smear cheese microbial surface
      consortium. To gain a better understanding of molecular adaptation due to low pH
      induced by lactose fermentation, the global gene expression profile of
      Corynebacterium glutamicum adapted to pH 5.7 with lactic acid under continuous
      growth in a chemostat was characterized by DNA microarray analysis. Expression of
      a total of 116 genes was increased and that of 90 genes was decreased compared to
      pH 7.5 without lactic acid, representing 7% of the genes in the genome. The up
      regulated genes encode mainly transcriptional regulators, proteins responsible
      for export, import, and metabolism, and several proteins of unknown function. As
      much as 45% of the up-regulated open reading frames code for hypothetical
      proteins. These results were validated using real-time reverse transcription-PCR.
      To characterize the functions of 38 up-regulated genes, 36 single-crossover
      disruption mutants were generated and analyzed for their lactic acid
      sensitivities. However, only a sigB knockout mutant showed a highly significant
      negative effect on growth at low pH, suggesting a function in organic-acid
      adaptation. A sigE mutant already displayed growth retardation at neutral pH but
      grew better at acidic pH than the sigB mutant. The lack of acid-sensitive
      phenotypes in 34 out of 36 disrupted genes suggests either a considerable
      redundancy in acid adaptation response or coincidental effects. Other up
      regulated genes included genes for ion transporters and metabolic pathways,
      including carbohydrate and respiratory metabolism. The enhanced expression of the
      nrd (ribonucleotide reductase) operon and a DNA ATPase repair protein implies a
      cellular response to combat acid-induced DNA damage. Surprisingly, multiple iron
      uptake systems (totaling 15% of the genes induced >or=2-fold) were induced at low
      pH. This induction was shown to be coincidental and could be attributed to iron
      sequestering effects in complex media at low pH.

PMID- 17526707
TI  - Characterization of the fucosylation pathway in the biosynthesis of
      glycopeptidolipids from Mycobacterium avium complex.
AB  - The cell envelopes of several species of nontuberculous mycobacteria, including
      the Mycobacterium avium complex, contain glycopeptidolipids (GPLs) as major
      glycolipid components. GPLs are highly antigenic surface molecules, and their
      variant oligosaccharides define each serotype of the M. avium complex. In the
      oligosaccharide portion of GPLs, the fucose residue is one of the major sugar
      moieties, but its biosynthesis remains unclear. To elucidate it, we focused on
      the 5.0-kb chromosomal region of the M. avium complex that includes five genes,
      two of which showed high levels of similarity to the genes involved in fucose
      synthesis. For the characterization of this region by deletion and expression
      analyses, we constructed a recombinant Mycobacterium smegmatis strain that
      possesses the rtfA gene of the M. avium complex to produce serovar 1 GPL. The
      results revealed that the 5.0-kb chromosomal region is responsible for the
      addition of the fucose residue to serovar 1 GPL and that the three genes mdhtA,
      merA, and gtfD are indispensable for the fucosylation. Functional
      characterization revealed that the gtfD gene encodes a glycosyltransferase that
      transfers a fucose residue via 1-->3 linkage to a rhamnose residue of serovar 1
      GPL. The other two genes, mdhtA and merA, contributed to the formation of the
      fucose residue and were predicted to encode the enzymes responsible for the
      synthesis of fucose from mannose based on their deduced amino acid sequences.
      These results indicate that the fucosylation pathway in GPL biosynthesis is
      controlled by a combination of the mdhtA, merA, and gtfD genes. Our findings may
      contribute to the clarification of the complex glycosylation pathways involved in
      forming the oligosaccharide portion of GPLs from the M. avium complex, which are
      structurally distinct.

PMID- 17526708
TI  - Identification of Pseudomonas syringae pv. syringae 61 type III secretion system
      Hrp proteins that can travel the type III pathway and contribute to the
      translocation of effector proteins into plant cells.
AB  - Pseudomonas syringae translocates effector proteins into plant cells via an Hrp1
      type III secretion system (T3SS). T3SS components HrpB, HrpD, HrpF, and HrpP were
      shown to be pathway substrates and to contribute to elicitation of the plant
      hypersensitive response and to translocation and secretion of the model effector
      AvrPto1.

PMID- 17526709
TI  - Functional incorporation of chimeric b subunits into F1Fo ATP synthase.
AB  - F(1)F(o) ATP synthases function by a rotary mechanism. The enzyme's peripheral
      stalk serves as the stator that holds the F(1) sector and its catalytic sites
      against the movement of the rotor. In Escherichia coli, the peripheral stalk is a
      homodimer of identical b subunits, but photosynthetic bacteria have open reading
      frames for two different b-like subunits thought to form heterodimeric b/b'
      peripheral stalks. Chimeric b subunit genes have been constructed by substituting
      sequence from the Thermosynechococcus elongatus b and b' genes in the E. coli
      uncF gene, encoding the b subunit. The recombinant genes were expressed alone and
      in combination in the E. coli deletion strain KM2 (Deltab). Although not all of
      the chimeric subunits were incorporated into F(1)F(o) ATP synthase complexes,
      plasmids expressing either chimeric b(E39-I86) or b'(E39-I86) were capable of
      functionally complementing strain KM2 (Deltab). Strains expressing these subunits
      grew better than cells with smaller chimeric segments, such as those expressing
      the b'(E39-D53) or b(L54-I86) subunit, indicating intragenic suppression. In
      general, the chimeric subunits modeled on the T. elongatus b subunit proved to be
      more stable than the b' subunit in vitro. Coexpression of the b(E39-I86) and
      b'(E39-I86) subunits in strain KM2 (Deltab) yielded F(1)F(o) complexes containing
      heterodimeric peripheral stalks composed of both subunits.

PMID- 17526710
TI  - The two-component regulatory system senX3-regX3 regulates phosphate-dependent
      gene expression in Mycobacterium smegmatis.
AB  - Phosphate import is required for the growth of mycobacteria and is regulated by
      environmental inorganic phosphate (P(i)) concentrations, although the mechanism
      of this regulation has not been characterized. The expression of genes involved
      in P(i) acquisition is frequently regulated by two-component regulatory systems
      (2CRs) consisting of a sensor histidine kinase and a DNA-binding response
      regulator. In this work, we have identified the senX3-regX3 2CR as a P(i)
      dependent regulator of genes involved in phosphate acquisition in Mycobacterium
      smegmatis. Characterization of senX3 mutants with different PhoA phenotypes
      suggests a dual role for SenX3 as a phosphatase or a phosphodonor for the
      response regulator RegX3, depending upon P(i) availability. Expression of PhoA
      activity required phosphorylation of RegX3, consistent with a role for
      phosphorylated RegX3 (RegX3 approximately P) as a transcriptional activator of
      phoA. Furthermore, purified RegX3 approximately P bound to promoter sequences
      from phoA, senX3, and the high-affinity phosphate transporter component pstS,
      demonstrating direct transcriptional control of all three genes. DNase I
      footprinting and primer extension analyses have further defined the DNA-binding
      region and transcriptional start site within the phoA promoter. A DNA motif
      consisting of an inverted repeat was identified in each of the promoters bound by
      RegX3 approximately P. Based upon our findings, we propose a model for P(i)
      regulated gene expression mediated by SenX3-RegX3 in mycobacteria.

PMID- 17526711
TI  - Human body temperature (37degrees C) increases the expression of iron,
      carbohydrate, and amino acid utilization genes in Escherichia coli K-12.
AB  - Using DNA microarrays, we identified 126 genes in Escherichia coli K-12 whose
      expression is increased at human body temperature (37 degrees C) compared to
      growth at 23 degrees C. Genes involved in the uptake and utilization of amino
      acids, carbohydrates, and iron dominated the list, supporting a model in which
      temperature serves as a host cue to increase expression of bacterial genes needed
      for growth. Using quantitative real-time PCR, we investigated the
      thermoregulatory response for representative genes in each of these three
      categories (hisJ, cysP, srlE, garP, fes, and cirA), along with the fimbrial gene
      papB. Increased expression at 37 degrees C compared to 23 degrees C was retained
      in both exponential and stationary phases for all of the genes and in most of the
      various media tested, supporting the relative importance of this cue in adapting
      to changing environments. Because iron acquisition is important for both growth
      and virulence, we analyzed the regulation of the iron utilization genes cirA and
      fes and found that growth in iron-depleted medium abrogated the thermoregulatory
      effect, with high-level expression at both temperatures, contrasting with papB
      thermoregulation, which was not greatly altered by limiting iron levels. A
      positive role for the environmental regulator H-NS was found for fes, cirA, hisJ,
      and srlE transcription, whereas it had a primarily negative effect on cysP and
      garP expression. Together, these studies indicate that temperature is a broadly
      used cue for regulating gene expression in E. coli and that H-NS regulates iron,
      carbohydrate, and amino acid utilization gene expression.

PMID- 17526712
TI  - IcsA surface presentation in Shigella flexneri requires the periplasmic
      chaperones DegP, Skp, and SurA.
AB  - A Shigella flexneri degP mutant, which was defective for plaque formation in
      Henle cell monolayers, had a reduced amount of IcsA detectable on the bacterial
      surface with antibody. However, the mutant secreted IcsA to the outer membrane at
      wild-type levels. This suggests that IcsA adopts an altered conformation in the
      outer membrane of the degP mutant with reduced exposure on the cell surface. IcsA
      is, therefore, unlikely to be accessible to actin-nucleating proteins within the
      eukaryotic cell cytoplasm, which is required for bacterial movement within the
      host cell and cell-to-cell spread. The degP mutant was somewhat more sensitive to
      detergents, antibiotics, and the antimicrobial peptide magainin, indicating that
      the degP phenotype was not limited to IcsA surface presentation. The plaque
      defect of the degP mutant, which is independent of DegP protease activity, was
      suppressed by overexpression of the periplasmic chaperone Skp but not by SurA. S.
      flexneri skp and surA mutants failed to form plaques in Henle cell monolayers and
      were defective in cell surface presentation and polar localization of IcsA.
      Therefore, the three periplasmic folding factors DegP, Skp, and SurA were all
      required for IcsA localization and plaque formation by S. flexneri.

PMID- 17526713
TI  - Drug-induced conformational changes in multidrug efflux transporter AcrB from
      Haemophilus influenzae.
AB  - In gram-negative bacteria, transporters belonging to the resistance-nodulation
      cell division (RND) superfamily of proteins are responsible for intrinsic
      multidrug resistance. Haemophilus influenzae, a gram-negative pathogen causing
      respiratory diseases in humans and animals, constitutively produces the multidrug
      efflux transporter AcrB (AcrB(HI)). Similar to other RND transporters AcrB(HI)
      associates with AcrA(HI), the periplasmic membrane fusion protein, and the outer
      membrane channel TolC(HI). Here, we report that AcrAB(HI) confers multidrug
      resistance when expressed in Escherichia coli and requires for its activity the
      E. coli TolC (TolC(EC)) protein. To investigate the intracellular dynamics of
      AcrAB(HI), single cysteine mutations were constructed in AcrB(HI) in positions
      previously identified as important for substrate recognition. The accessibility
      of these strategically positioned cysteines to the hydrophilic thiol-reactive
      fluorophore fluorescein-5-maleimide (FM) was studied in vivo in the presence of
      various substrates of AcrAB(HI) and in the presence or absence of AcrA(HI) and
      TolC(EC). We report that the reactivity of specific cysteines with FM is affected
      by the presence of some but not all substrates. Our results suggest that
      substrates induce conformational changes in AcrB(HI).

PMID- 17526714
TI  - FepA- and TonB-dependent bacteriophage H8: receptor binding and genomic sequence.
AB  - H8 is derived from a collection of Salmonella enterica serotype Enteritidis
      bacteriophage. Its morphology and genomic structure closely resemble those of
      bacteriophage T5 in the family Siphoviridae. H8 infected S. enterica serotypes
      Enteritidis and Typhimurium and Escherichia coli by initial adsorption to the
      outer membrane protein FepA. Ferric enterobactin inhibited H8 binding to E. coli
      FepA (50% inhibition concentration, 98 nM), and other ferric catecholate
      receptors (Fiu, Cir, and IroN) did not participate in phage adsorption. H8
      infection was TonB dependent, but exbB mutations in Salmonella or E. coli did not
      prevent infection; only exbB tolQ or exbB tolR double mutants were resistant to
      H8. Experiments with deletion and substitution mutants showed that the receptor
      phage interaction first involves residues distributed over the protein's outer
      surface and then narrows to the same charged (R316) or aromatic (Y260) residues
      that participate in the binding and transport of ferric enterobactin and colicins
      B and D. These data rationalize the multifunctionality of FepA: toxic ligands
      like bacteriocins and phage penetrate the outer membrane by parasitizing residues
      in FepA that are adapted to the transport of the natural ligand, ferric
      enterobactin. DNA sequence determinations revealed the complete H8 genome of
      104.4 kb. A total of 120 of its 143 predicted open reading frames (ORFS) were
      homologous to ORFS in T5, at a level of 84% identity and 89% similarity. As in
      T5, the H8 structural genes clustered on the chromosome according to their
      function in the phage life cycle. The T5 genome contains a large section of DNA
      that can be deleted and that is absent in H8: compared to T5, H8 contains a 9,000
      bp deletion in the early region of its chromosome, and nine potentially unique
      gene products. Sequence analyses of the tail proteins of phages in the same
      family showed that relative to pb5 (Oad) of T5 and Hrs of BF23, the FepA-binding
      protein (Rbp) of H8 contains unique acidic and aromatic residues. These side
      chains may promote binding to basic and aromatic residues in FepA that normally
      function in the adsorption of ferric enterobactin. Furthermore, a predicted H8
      tail protein showed extensive identity and similarity to pb2 of T5, suggesting
      that it also functions in pore formation through the cell envelope. The variable
      region of this protein contains a potential TonB box, intimating that it
      participates in the TonB-dependent stage of the phage infection process.

PMID- 17526715
TI  - The phage phi29 membrane protein p16.7, involved in DNA replication, is required
      for efficient ejection of the viral genome.
AB  - It is becoming clear that in vivo phage DNA ejection is not a mere passive
      process. In most cases, both phage and host proteins seem to be involved in
      pulling at least part of the viral DNA inside the cell. The DNA ejection
      mechanism of Bacillus subtilis bacteriophage phi29 is a two-step process where
      the linear DNA penetrates the cell with a right-left polarity. In the first step
      approximately 65% of the DNA is pushed into the cell. In the second step, the
      remaining DNA is actively pulled into the cytoplasm. This step requires protein
      p17, which is encoded by the right-side early operon that is ejected during the
      first push step. The membrane protein p16.7, also encoded by the right-side early
      operon, is known to play an important role in membrane-associated phage DNA
      replication. In this work we show that, in addition, p16.7 is required for
      efficient execution of the second pull step of DNA ejection.

PMID- 17526716
TI  - Differential interaction of Aggregatibacter (Actinobacillus)
      actinomycetemcomitans LsrB and RbsB proteins with autoinducer 2.
AB  - Our previous studies showed that the Aggregatibacter actinomycetemcomitans RbsB
      protein interacts with cognate and heterologous autoinducer 2 (AI-2) signals and
      suggested that the rbsDABCK operon encodes a transporter that may internalize AI
      2 (D. James et al., Infect. Immun. 74:4021-4029, 2006.). However, A.
      actinomycetemcomitans also possesses genes related to the lsr operon of
      Salmonella enterica serovar Typhimurium which function to import AI-2. Here, we
      show that A. actinomycetemcomitans LsrB protein competitively inhibits the
      interaction of the Vibrio harveyi AI-2 receptor (LuxP) with AI-2 from either A.
      actinomycetemcomitans or V. harveyi. Interestingly, LsrB was a more potent
      inhibitor of LuxP interaction with AI-2 from V. harveyi whereas RbsB competed
      more effectively with LuxP for A. actinomycetemcomitans AI-2. Inactivation of
      lsrB in wild-type A. actinomycetemcomitans or in an isogenic RbsB-deficient
      strain reduced the rate by which intact bacteria depleted A.
      actinomycetemcomitans AI-2 from solution. Consistent with the results from the
      LuxP competition experiments, the LsrB-deficient strain depleted AI-2 to a lesser
      extent than the RbsB-deficient organism. Inactivation of both lsrB and rbsB
      virtually eliminated the ability of the organism to remove AI-2 from the
      extracellular environment. These results suggest that A. actinomycetemcomitans
      possesses two proteins that differentially interact with AI-2 and may function to
      inactivate or facilitate internalization of AI-2.

PMID- 17526717
TI  - Bifunctional CTP:inositol-1-phosphate cytidylyltransferase/CDP-inositol:inositol
      1-phosphate transferase, the key enzyme for di-myo-inositol-phosphate synthesis
      in several (hyper)thermophiles.
AB  - The pathway for the synthesis of di-myo-inositol-phosphate (DIP) was recently
      elucidated on the basis of the detection of the relevant activities in cell
      extracts of Archaeoglobus fulgidus and structural characterization of products by
      nuclear magnetic resonance (NMR) (N. Borges, L. G. Goncalves, M. V. Rodrigues, F.
      Siopa, R. Ventura, C. Maycock, P. Lamosa, and H. Santos, J. Bacteriol. 188:8128
      8135, 2006). Here, a genomic approach was used to identify the genes involved in
      the synthesis of DIP. Cloning and expression in Escherichia coli of the putative
      genes for CTP:l-myo-inositol-1-phosphate cytidylyltransferase and DIPP (di-myo
      inositol-1,3'-phosphate-1'-phosphate, a phosphorylated form of DIP) synthase from
      several (hyper)thermophiles (A. fulgidus, Pyrococcus furiosus, Thermococcus
      kodakaraensis, Aquifex aeolicus, and Rubrobacter xylanophilus) confirmed the
      presence of those activities in the gene products. The DIPP synthase activity was
      part of a bifunctional enzyme that catalyzed the condensation of CTP and l-myo
      inositol-1-phosphate into CDP-l-myo-inositol, as well as the synthesis of DIPP
      from CDP-l-myo-inositol and l-myo-inositol-1-phosphate. The cytidylyltransferase
      was absolutely specific for CTP and l-myo-inositol-1-P; the DIPP synthase domain
      used only l-myo-inositol-1-phosphate as an alcohol acceptor, but CDP-glycerol, as
      well as CDP-l-myo-inositol and CDP-d-myo-inositol, were recognized as alcohol
      donors. Genome analysis showed homologous genes in all organisms known to
      accumulate DIP and for which genome sequences were available. In most cases, the
      two activities (l-myo-inositol-1-P cytidylyltransferase and DIPP synthase) were
      fused in a single gene product, but separate genes were predicted in Aeropyrum
      pernix, Thermotoga maritima, and Hyperthermus butylicus. Additionally, using l
      myo-inositol-1-phosphate labeled on C-1 with carbon 13, the stereochemical
      configuration of all the metabolites involved in DIP synthesis was established by
      NMR analysis. The two inositol moieties in DIP had different stereochemical
      configurations, in contradiction of previous reports. The use of the designation
      di-myo-inositol-1,3'-phosphate is recommended to facilitate tracing individual
      carbon atoms through metabolic pathways.

PMID- 17526720
TI  - The shifting baseline of northern fur seal ecology in the northeast Pacific
      Ocean.
AB  - Historical data provide a baseline against which to judge the significance of
      recent ecological shifts and guide conservation strategies, especially for
      species decimated by pre-20th century harvesting. Northern fur seals (NFS;
      Callorhinus ursinus) are a common pinniped species in archaeological sites from
      southern California to the Aleutian Islands, yet today they breed almost
      exclusively on offshore islands at high latitudes. Harvest profiles from
      archaeological sites contain many unweaned pups, confirming the presence of
      temperate-latitude breeding colonies in California, the Pacific Northwest, and
      the eastern Aleutian Islands. Isotopic results suggest that prehistoric NFS fed
      offshore across their entire range, that California populations were distinct
      from populations to the north, and that populations breeding at temperate
      latitudes in the past used a different reproductive strategy than modern
      populations. The extinction of temperate-latitude breeding populations was
      asynchronous geographically. In southern California, the Pacific Northwest, and
      the eastern Aleutians, NFS remained abundant in the archaeological record up to
      the historical period approximately 200 years B.P.; thus their regional collapse
      is plausibly attributed to historical hunting or some other anthropogenic
      ecosystem disturbance. In contrast, NFS populations in central and northern
      California collapsed at approximately 800 years B.P., long before European
      contact. The relative roles of human hunting versus climatic factors in
      explaining this ecological shift are unclear, as more paleoclimate information is
      needed from the coastal zone.

PMID- 17526721
TI  - New Trypanosoma cruzi repeated element that shows site specificity for insertion.
AB  - A new family of site-specific repeated elements identified in Trypanosoma cruzi,
      which we named TcTREZO, is described here. TcTREZO appears to be a composite
      repeated element, since three subregions may be defined within it on the basis of
      sequence similarities with other T. cruzi sequences. Analysis of the distribution
      of TcTREZO in the genome clearly indicates that it displays site specificity for
      insertion. Most TcTREZO elements are flanked by conserved sequences. There is a
      highly conserved 68-bp sequence at the 5' end of the element and a sequence
      domain of approximately 500 bp without a well-defined borderline at the 3' end.
      Northern blot hybridization and reverse transcriptase PCR analyses showed that
      TcTREZO transcripts are expressed as oligo(A)-terminated transcripts whose length
      corresponds to the unit size of the element (1.6 kb). Transcripts of
      approximately 0.2 kb derived from a small part of TcTREZO are also detected in
      steady-state RNA. TcTREZO transcripts are unspliced and not translated. The copy
      number of TcTREZO sequences was estimated to be approximately 173 copies per
      haploid genome. TcTREZO appears to have been assembled by insertions of sequences
      into a progenitor element. Once associated with each other, these subunits were
      amplified as a new transposable element. TcTREZO shows site specificity for
      insertion, suggesting that a sequence-specific endonuclease could be responsible
      for its insertion at a unique site.

PMID- 17526722
TI  - Saccharomyces cerevisiae vacuole in zinc storage and intracellular zinc
      distribution.
AB  - Previous studies of the yeast Saccharomyces cerevisiae indicated that the vacuole
      is a major site of zinc storage in the cell. However, these studies did not
      address the absolute level of zinc that was stored in the vacuole nor did they
      examine the abundances of stored zinc in other compartments of the cell. In this
      report, we describe an analysis of the cellular distribution of zinc by use of
      both an organellar fractionation method and an electron probe X-ray
      microanalysis. With these methods, we determined that zinc levels in the vacuole
      vary with zinc status and can rise to almost 100 mM zinc (i.e., 7 x 10(8) atoms
      of vacuolar zinc per cell). Moreover, this zinc can be mobilized effectively to
      supply the needs of as many as eight generations of progeny cells under zinc
      starvation conditions. While the Zrc1 and Cot1 zinc transporters are essential
      for zinc uptake into the vacuole under steady-state growth conditions, additional
      transporters help mediate zinc uptake into the vacuole during "zinc shock," when
      zinc-limited cells are resupplied with zinc. In addition, we found that other
      compartments of the cell do not provide significant stores of zinc. In
      particular, zinc accumulation in mitochondria is low and is homeostatically
      regulated independently of vacuolar zinc storage. Finally, we observed a strong
      correlation between zinc status and the levels of magnesium and phosphorus
      accumulated in cells. Our results implicate zinc as a major determinant of the
      ability of the cell to store these other important nutrients.

PMID- 17526723
TI  - Antisense intergenic transcription precedes Igh D-to-J recombination and is
      controlled by the intronic enhancer Emu.
AB  - V(D)J recombination is believed to be regulated by alterations in chromatin
      accessibility to the recombinase machinery, but the mechanisms responsible remain
      unclear. We previously proposed that antisense intergenic transcription,
      activated throughout the mouse Igh VH region in pro-B cells, remodels chromatin
      for VH-to-DJH recombination. Using RNA fluorescence in situ hybridization, we now
      show that antisense intergenic transcription occurs throughout the Igh DHJH
      region before D-to-J recombination, indicating that this is a widespread process
      in V(D)J recombination. Transcription initiates near the Igh intronic enhancer
      Emu and is abrogated in mice lacking this enhancer, indicating that Emu regulates
      DH antisense transcription. Emu was recently demonstrated to regulate DH-to-JH
      recombination of the Igh locus. Together, these data suggest that Emu controls DH
      to-JH recombination by activating this form of germ line Igh transcription, thus
      providing a long-range, processive mechanism by which Emu can regulate chromatin
      accessibility throughout the DH region. In contrast, Emu deletion has no effect
      on VH antisense intergenic transcription, which is rarely associated with DH
      antisense transcription, suggesting differential regulation and separate roles
      for these processes at sequential stages of V(D)J recombination. These results
      support a directive role for antisense intergenic transcription in enabling
      access to the recombination machinery.

PMID- 17526724
TI  - Aberrant regulation of hematopoiesis by T cells in BAZF-deficient mice.
AB  - The BAZF (BCL-6b) protein is highly similar to the BCL-6 transcriptional
      repressor. While BCL-6 has been characterized extensively, relatively little is
      known about the normal function of BAZF. In order to understand the physiological
      role of BAZF, we created BAZF-deficient mice. Unlike BCL-6-deficient mice, BAZF
      deficient mice are healthy and normal in size. However, BAZF-deficient mice have
      a hematopoietic progenitor phenotype that is almost identical to that of BCL-6
      deficient mice. Compared to wild-type mice, both BAZF-deficient and BCL-6
      deficient mice have greatly reduced numbers of cycling hematopoietic progenitor
      cells (HPC) in the BM and greatly increased numbers of cycling HPC in the spleen.
      In contrast to HPC from wild-type mice, HPC from BAZF-deficient and BCL-6
      deficient mice are resistant to chemokine-induced myelosuppression and do not
      show a synergistic growth response to granulocyte-macrophage colony-stimulating
      factor plus stem cell factor. Depletion of CD8 T cells in BAZF-deficient mice
      reverses several of the hematopoietic defects in these mice. Since both BAZF- and
      BCL-6-deficient mice have defects in CD8 T-cell differentiation, we hypothesize
      that both BCL-6 and BAZF regulate HPC homeostasis by an indirect pathway
      involving CD8 T cells.

PMID- 17526725
TI  - The locus control region activates serpin gene expression through recruitment of
      liver-specific transcription factors and RNA polymerase II.
AB  - The human serine protease inhibitor (serpin) gene cluster at 14q32.1 comprises 11
      serpin genes, many of which are expressed specifically in hepatic cells. Previous
      studies identified a locus control region (LCR) upstream of the human alpha1
      antitrypsin (alpha1AT) gene that is required for gene activation, chromatin
      remodeling, and histone acetylation throughout the proximal serpin subcluster.
      Here we show that the LCR interacts with multiple liver-specific transcription
      factors, including hepatocyte nuclear factor 3beta (HNF-3beta), HNF-6alpha,
      CCAAT/enhancer binding protein alpha (C/EBPalpha), and C/EBPbeta. RNA polymerase
      II is also recruited to the locus through the LCR. Nongenic transcription at both
      the LCR and an upstream regulatory region was detected, but the deletion of the
      LCR abolished transcription at both sites. The deletion of HNF-3 and HNF-6
      binding sites within the LCR reduced histone acetylation at both the LCR and the
      upstream regulatory region and decreased the transcription of the alpha1AT,
      corticosteroid binding globulin, and protein Z-dependent protease inhibitor
      genes. These results suggest that the LCR activates genes in the proximal serpin
      subcluster by recruiting liver-specific transcription factors and components of
      the general transcription machinery to regulatory regions upstream of the
      alpha1AT gene.

PMID- 17526726
TI  - Specificity and complexity of the Caenorhabditis elegans innate immune response.
AB  - In response to infection, Caenorhabditis elegans produces an array of
      antimicrobial proteins. To understand the C. elegans immune response, we have
      investigated the regulation of a large, representative sample of candidate
      antimicrobial genes. We found that all these putative antimicrobial genes are
      expressed in tissues exposed to the environment, a position from which they can
      ward off infection. Using RNA interference to inhibit the function of immune
      signaling pathways in C. elegans, we found that different immune response
      pathways regulate expression of distinct but overlapping sets of antimicrobial
      genes. We also show that different bacterial pathogens regulate distinct but
      overlapping sets of antimicrobial genes. The patterns of genes induced by
      pathogens do not coincide with any single immune signaling pathway. Thus, even in
      this simple model system for innate immunity, striking specificity and complexity
      exist in the immune response. The unique patterns of antimicrobial gene
      expression observed when C. elegans is exposed to different pathogens or when
      different immune signaling pathways are perturbed suggest that a large set of yet
      to be identified pathogen recognition receptors (PRRs) exist in the nematode.
      These PRRs must interact in a complicated fashion to induce a unique set of
      antimicrobial genes. We also propose the existence of an "antimicrobial
      fingerprint," which will aid in assigning newly identified C. elegans innate
      immunity genes to known immune signaling pathways.

PMID- 17526727
TI  - Analysis of transcriptional activation at a distance in Saccharomyces cerevisiae.
AB  - Most fundamental aspects of transcription are conserved among eukaryotes. One
      striking difference between yeast Saccharomyces cerevisiae and metazoans,
      however, is the distance over which transcriptional activation occurs. In S.
      cerevisiae, upstream activation sequences (UASs) are generally located within a
      few hundred base pairs of a target gene, while in Drosophila and mammals,
      enhancers are often several kilobases away. To study the potential for long
      distance activation in S. cerevisiae, we constructed and analyzed reporters in
      which the UAS-TATA distance varied. Our results show that UASs lose the ability
      to activate normal transcription as the UAS-TATA distance increases.
      Surprisingly, transcription does initiate, but proximally to the UAS, regardless
      of its location. To identify factors affecting long-distance activation, we
      screened for mutants allowing activation of a reporter when the UAS-TATA distance
      is 799 bp. These screens identified four loci, SIN4, SPT2, SPT10, and HTA1-HTB1,
      with sin4 mutations being the strongest. Our results strongly suggest that long
      distance activation in S. cerevisiae is normally limited by Sin4 and other
      factors and that this constraint plays a role in ensuring UAS-core promoter
      specificity in the compact S. cerevisiae genome.

PMID- 17526728
TI  - NuA4-directed chromatin transactions throughout the Saccharomyces cerevisiae
      genome.
AB  - Two of the major histone acetyltransferases in Saccharomyces cerevisiae are NuA4
      and SAGA, which acetylate histones H4 and H3, respectively. Acetylated H3 and H4
      tails have been implicated in binding bromodomain proteins, including Bdf1. Bdf1
      interacts with the general transcription factor TFIID, which might promote
      preinitiation complex (PIC) assembly. Bdf1 also interacts with the SWR complex
      (SWR-C). SWR-C is responsible for the deposition of the histone H2A variant
      H2A.Z. The placement of these interactions into a connected pathway of PIC
      assembly has not been fully established. Moreover, it is not known how widespread
      and how variable such a pathway might be on a genomic scale. Here we provide
      genomic evidence for S. cerevisiae that PIC assembly (TFIID occupancy) and
      chromatin remodeling (SWR-C and H2A.Z occupancy) are linked in large part to NuA4
      directed H4 acetylation and subsequent Bdf1 binding, rather than through SAGA
      directed H3 acetylation. Bdf1 and its homolog Bdf2 tend to have distinct
      locations in the genome. However, the deletion of BDF1 leads to the accumulation
      of Bdf2 at Bdf1-vacated sites. Thus, while Bdf1 and Bdf2 are at least partially
      redundant in function, their functions in the genome are geographically distinct.

PMID- 17526729
TI  - Hypoxia-inducible factor linked to differential kidney cancer risk seen with type
      2A and type 2B VHL mutations.
AB  - Clear cell carcinoma of the kidney is a major cause of mortality in patients with
      von Hippel-Lindau (VHL) disease, which is caused by germ line mutations that
      inactivate the VHL tumor suppressor gene. Biallelic VHL inactivation, due to
      mutations or hypermethylation, is also common in sporadic clear cell renal
      carcinomas. The VHL gene product, pVHL, is part of a ubiquitin ligase complex
      that targets the alpha subunits of the heterodimeric transcription factor hypoxia
      inducible factor (HIF) for destruction under well-oxygenated conditions. All VHL
      mutations linked to classical VHL disease compromise this pVHL function although
      some missense mutations result in a low risk of kidney cancer (type 2A VHL
      disease) while others result in a high risk (type 2B VHL disease). We found that
      type 2A mutants were less defective than type 2B mutants when reintroduced into
      VHL-/- renal carcinoma cells with respect to HIF regulation. A stabilized version
      of HIF2alpha promoted tumor growth by VHL-/- cells engineered to produce type 2A
      mutants, while knock-down of HIF2alpha in cells producing type 2B mutants had the
      opposite effect. Therefore, quantitative differences with respect to HIF
      deregulation are sufficient to account for the differential risks of kidney
      cancer linked to VHL mutations.

PMID- 17526730
TI  - Conditional deletion of focal adhesion kinase leads to defects in ventricular
      septation and outflow tract alignment.
AB  - To examine a role for focal adhesion kinase (FAK) in cardiac morphogenesis, we
      generated a line of mice with a conditional deletion of FAK in nkx2-5-expressing
      cells (herein termed FAKnk mice). FAKnk mice died shortly after birth, likely
      resulting from a profound subaortic ventricular septal defect and associated
      malalignment of the outflow tract. Additional less penetrant phenotypes included
      persistent truncus arteriosus and thickened valve leaflets. Thus, conditional
      inactivation of FAK in nkx2-5-expressing cells leads to the most common
      congenital heart defect that is also a subset of abnormalities associated with
      tetralogy of Fallot and the DiGeorge syndrome. No significant differences in
      proliferation or apoptosis between control and FAKnk hearts were observed.
      However, decreased myocardialization was observed for the conal ridges of the
      proximal outflow tract in FAKnk hearts. Interestingly, chemotaxis was
      significantly attenuated in isolated FAK-null cardiomyocytes in comparison to
      genetic controls, and these effects were concomitant with reduced tyrosine
      phosphorylation of Crk-associated substrate (CAS). Thus, it is possible that
      ventricular septation and appropriate outflow tract alignment is dependent, at
      least in part, upon FAK-dependent CAS activation and subsequent induction of
      polarized myocyte movement into the conal ridges. Future studies will be
      necessary to determine the precise contributions of the additional nkx2-5-derived
      lineages to the phenotypes observed.

PMID- 17526731
TI  - A double-bromodomain protein, FSH-S, activates the homeotic gene ultrabithorax
      through a critical promoter-proximal region.
AB  - More than a dozen trithorax group (trxG) proteins are involved in activation of
      Drosophila HOX genes. How they act coordinately to integrate signals from
      distantly located enhancers is not fully understood. The female sterile (1)
      homeotic (fs(1)h) gene is one of the trxG genes that is most critical for
      Ultrabithorax (Ubx) activation. We show that one of the two double-bromodomain
      proteins encoded by fs(1)h acts as an essential factor in the Ubx proximal
      promoter. First, overexpression of the small isoform FSH-S, but not the larger
      one, can induce ectopic expression of HOX genes and cause body malformation.
      Second, FSH-S can stimulate Ubx promoter in cultured cells through a critical
      proximal region in a bromodomain-dependent manner. Third, purified FSH-S can bind
      specifically to a motif within this region that was previously known as the ZESTE
      site. The physiological relevance of FSH-S is ascertained using transgenic
      embryos containing a modified Ubx proximal promoter and chromatin
      immunoprecipitation. In addition, we show that FSH-S is involved in
      phosphorylation of itself and other regulatory factors. We suggest that FSH-S
      acts as a critical component of a regulatory circuitry mediating long-range
      effects of distant enhancers.

PMID- 17526732
TI  - The transcription corepressor LEUNIG interacts with the histone deacetylase HDA19
      and mediator components MED14 (SWP) and CDK8 (HEN3) to repress transcription.
AB  - Transcription corepressors are general regulators controlling the expression of
      genes involved in multiple signaling pathways and developmental programs.
      Repression is mediated through mechanisms including the stabilization of a
      repressive chromatin structure over control regions and regulation of Mediator
      function inhibiting RNA polymerase II activity. Using whole-genome arrays we show
      that the Arabidopsis thaliana corepressor LEUNIG, a member of the GroTLE
      transcription corepressor family, regulates the expression of multiple targets in
      vivo. LEUNIG has a role in the regulation of genes involved in a number of
      different physiological processes including disease resistance, DNA damage
      response, and cell signaling. We demonstrate that repression of in vivo LEUNIG
      targets is achieved through histone deacetylase (HDAC)-dependent and -independent
      mechanisms. HDAC-dependent mechanisms involve direct interaction with HDA19, a
      class 1 HDAC, whereas an HDAC-independent repression activity involves
      interactions with the putative Arabidopsis Mediator components AtMED14/SWP and
      AtCDK8/HEN3. We suggest that changes in chromatin structure coupled with
      regulation of Mediator function are likely to be utilized by LEUNIG in the
      repression of gene transcription.

PMID- 17526733
TI  - Enhanced sensitivity to cholera toxin in ADP-ribosylarginine hydrolase-deficient
      mice.
AB  - Cholera toxin (CT) produced by Vibrio cholerae causes the devastating diarrhea of
      cholera by catalyzing the ADP-ribosylation of the alpha subunit of the intestinal
      Gs protein (Gsalpha), leading to characteristic water and electrolyte losses.
      Mammalian cells contain ADP-ribosyltransferases similar to CT and an ADP
      ribosyl(arginine)protein hydrolase (ADPRH), which cleaves the ADP-ribose
      (arginine)protein bond, regenerating native protein and completing an ADP
      ribosylation cycle. We hypothesized that ADPRH might counteract intoxication by
      reversing the ADP-ribosylation of Gsalpha. Effects of intoxication on murine
      ADPRH-/- cells were greater than those on wild-type cells and were significantly
      reduced by overexpression of wild-type ADPRH in ADPRH-/- cells, as evidenced by
      both ADP-ribose-arginine content and Gsalpha modification. Similarly, intestinal
      loops in the ADPRH-/- mouse were more sensitive than their wild-type counterparts
      to toxin effects on fluid accumulation, Gsalpha modification, and ADP
      ribosylarginine content. Thus, CT-catalyzed ADP-ribosylation of cell proteins can
      be counteracted by ADPRH, which could function as a modifier gene in disease.
      Further, our study demonstrates that enzymatic cross talk exists between
      bacterial toxin ADP-ribosyltransferases and host ADP-ribosylation cycles. In
      disease, toxin-catalyzed ADP-ribosylation overwhelms this potential host defense
      system, resulting in persistence of ADP-ribosylation and intoxication of the
      cell.

PMID- 17526734
TI  - Haploinsufficiency of Mdm2 and Mdm4 in tumorigenesis and development.
AB  - The tumor suppressor p53 is inactivated by multiple mechanisms that include
      mutations of the p53 gene itself and increased levels of the p53 inhibitors MDM2
      and MDM4. Mice lacking Mdm2 or Mdm4 exhibit embryo-lethal phenotypes that are
      completely rescued by concomitant deletion of p53. Here we show that Mdm2 and
      Mdm4 haploinsufficiency leads to increased p53 activity, exhibited as increased
      sensitivity to DNA damage and decreased transformation potential. Moreover, in in
      vivo tumor development, Emu-myc Mdm4+/- mice show a delayed onset of B-cell
      lymphomas compared to Emu-myc mice. Additionally, Mdm2+/- Mdm4+/- double
      heterozygous mice are not viable and exhibit defects in hematopoiesis and
      cerebellar development. The defects in Mdm2+/- Mdm4+/- mice are corrected by
      deletion of a single p53 allele. These findings highlight the exquisite
      sensitivity of p53 to Mdm2 and Mdm4 levels and suggest that some cell types may
      be more sensitive to therapeutic drugs that inhibit the Mdm-p53 interaction.

PMID- 17526735
TI  - Mek1 kinase is regulated to suppress double-strand break repair between sister
      chromatids during budding yeast meiosis.
AB  - Mek1 is a meiosis-specific kinase in budding yeast which promotes recombination
      between homologous chromosomes by suppressing double-strand break (DSB) repair
      between sister chromatids. Previous work has shown that in the absence of the
      meiosis-specific recombinase gene, DMC1, cells arrest in prophase due to
      unrepaired DSBs and that Mek1 kinase activity is required in this situation to
      prevent repair of the breaks using sister chromatids. This work demonstrates that
      Mek1 is activated in response to DSBs by autophosphorylation of two conserved
      threonines, T327 and T331, in the Mek1 activation loop. Using a version of Mek1
      that can be conditionally dimerized during meiosis, Mek1 function was shown to be
      promoted by dimerization, perhaps as a way of enabling autophosphorylation of the
      activation loop in trans. A putative HOP1-dependent dimerization domain within
      the C terminus of Mek1 has been identified. Dimerization alone, however, is
      insufficient for activation, as DSBs and Mek1 recruitment to the meiosis-specific
      chromosomal core protein Red1 are also necessary. Phosphorylation of S320 in the
      activation loop inhibits sister chromatid repair specifically in dmc1Delta
      arrested cells. Ectopic dimerization of Mek1 bypasses the requirement for S320
      phosphorylation, suggesting this phosphorylation is necessary for maintenance of
      Mek1 dimers during checkpoint-induced arrest.

PMID- 17526736
TI  - Splicing regulator SC35 is essential for genomic stability and cell proliferation
      during mammalian organogenesis.
AB  - The members of the SR family of splicing regulators were initially characterized
      for their critical roles in constitutive and regulated splicing. They are
      implicated in different aspects of gene expression processes, including
      transcription, RNA stability, mRNA transport, and translational control. While
      knockout studies have demonstrated their essential functions during animal
      development, the pathway(s) leading to a specific cellular phenotype remains
      poorly understood. We report here that the SR protein SC35 controls cell
      proliferation during pituitary gland development but is completely dispensable in
      terminal differentiated mature cardiomyocytes in mice. We show that loss of SC35
      in mouse embryonic fibroblasts induces G2/M cell cycle arrest and genomic
      instability, resulting at least in part from p53 hyperphosphorylation and
      hyperacetylation. While p53 hyperphosphorylation appears related to ATM
      activation, its hyperacetylation has been attributed to the increased expression
      of the acetyltransferase gene p300 and the aberrant splicing of the deacetylase
      gene SirT1. These findings reveal the involvement of SC35 in specific pathways in
      regulating cell proliferation and genomic stability during mammalian
      organogenesis and suggest its potential function in tumorigenesis.

PMID- 17526737
TI  - Integrin-linked kinase controls Notch1 signaling by down-regulation of protein
      stability through Fbw7 ubiquitin ligase.
AB  - Integrin-linked kinase (ILK) is a scaffold and protein kinase that acts as a
      pivotal effector in integrin signaling for various cellular functions. In this
      study, we found that ILK remarkably reduced the protein stability of Notch1
      through Fbw7. The kinase activity of ILK was essential for the inhibition of
      Notch1 signaling. Notably, the protein level and transcriptional activity of the
      endogenous Notch1 intracellular domain (Notch1-IC) were higher in ILK-null cells
      than in ILK wild-type cells, and the level of endogenous Notch1-IC was increased
      by the blocking of the proteasome, suggesting that ILK enhances the proteasomal
      degradation of Notch1-IC. ILK directly bound and phosphorylated Notch1-IC,
      thereby facilitating proteasomal protein degradation through Fbw7. Furthermore,
      we found down-regulation of Notch1-IC and up-regulation of ILK in basal cell
      carcinoma and melanoma patients but not in squamous cell carcinoma patients.
      These results suggest that ILK down-regulated the protein stability of Notch1-IC
      through the ubiquitin-proteasome pathway by means of Fbw7.

PMID- 17526738
TI  - Critical contacts between the eukaryotic initiation factor 2B (eIF2B) catalytic
      domain and both eIF2beta and -2gamma mediate guanine nucleotide exchange.
AB  - Diverse guanine nucleotide exchange factors (GEFs) regulate the activity of GTP
      binding proteins. One of the most complicated pairs is eukaryotic initiation
      factor 2B (eIF2B) and eIF2, which function during protein synthesis initiation in
      eukaryotes. We have mutated conserved surface residues within the eIF2B GEF
      domain, located at the eIF2Bepsilon C terminus. Extensive genetic and biochemical
      characterization established how these residues contribute to GEF activity. We
      find that the universally conserved residue E569 is critical for activity and
      that even a conservative E569D substitution is lethal in vivo. Several mutations
      within residues close to E569 have no discernible effect on growth or GCN4
      expression, but an alanine substitution at the adjacent L568 is cold sensitive
      and deregulates GCN4 activity at 15 degrees C. The mutation of W699, found on a
      separate surface approximately 40 A from E569, is also lethal. Binding studies
      show that W699 is critical for interaction with eIF2beta, while L568 and E569 are
      not. In contrast, all three residues are critical for interaction with eIF2gamma.
      These data show that multiple contacts between eIF2gamma and eIF2Bepsilon mediate
      nucleotide exchange.

PMID- 17526739
TI  - Wwp2-mediated ubiquitination of the RNA polymerase II large subunit in mouse
      embryonic pluripotent stem cells.
AB  - Ubiquitination and the degradation of the large subunit of RNA polymerase II,
      Rpb1, is not only involved in DNA damage-induced arrest but also in other
      transcription-obstructing events. However, the ubiquitin ligases responsible for
      DNA damage-independent processes in mammalian cells remain to be identified.
      Here, we identified Wwp2, a mouse HECT domain ubiquitin E3 ligase, as a novel
      ubiquitin ligase of Rpb1. We found that Wwp2 specifically interacted with mouse
      Rpb1 and targeted it for ubiquitination both in vitro and in vivo. Interestingly,
      the interaction with and ubiquitination of Rpb1 was dependent neither on its
      phosphorylation state nor on DNA damage. However, the enzymatic activity of Wwp2
      was absolutely required for its ubiquitin modification of Rpb1. Furthermore, our
      study indicates that the interaction between Wwp2 and Rpb1 was mediated through
      WW domain of Wwp2 and C-terminal domain of Rpb1, respectively. Strikingly,
      downregulation of Wwp2 expression compromised Rpb1 ubiquitination and elevated
      its intracellular steady-state protein level significantly. Importantly, we
      identified six lysine residues in the C-terminal domain of Rpb1 as ubiquitin
      acceptor sites mediated by Wwp2. These results indicate that Wwp2 plays an
      important role in regulating expression of Rpb1 in normal physiological
      conditions.

PMID- 17526740
TI  - The E295K DNA polymerase beta gastric cancer-associated variant interferes with
      base excision repair and induces cellular transformation.
AB  - Approximately 30% of human tumors examined for mutations in polymerase beta (pol
      beta) appear to express pol beta variant proteins (D. Starcevic, S. Dalal, and J.
      B. Sweasy, Cell Cycle 3:998-1001, 2004). Many of these variants result from a
      single amino acid substitution. We have previously shown that the K289M and I260M
      colon and prostate cancer variants, respectively, induce cellular transformation
      most likely due to sequence-specific mutator activity (S. Dalal et al.,
      Biochemistry 44:15664-15673, 2005; T. Lang et al., Proc. Natl. Acad. Sci. USA
      101:6074-6079, 2004; J. B. Sweasy et al., Proc. Natl. Acad. Sci. USA 102:14350
      14355, 2005). In the work described here, we show that the E295K gastric
      carcinoma pol beta variant acts in a dominant-negative manner by interfering with
      base excision repair. This leads to an increase in sister chromatid exchanges.
      Expression of the E295K variant also induces cellular transformation. Our data
      suggest that unfilled gaps are channeled into a homology-directed repair pathway
      that could lead to genomic instability. The results indicate that base excision
      repair is critical for maintaining genome stability and could therefore be a
      tumor suppressor mechanism.

PMID- 17526741
TI  - Induction of nitric oxide synthase and activation of signaling proteins in
      Anopheles mosquitoes by the malaria pigment, hemozoin.
AB  - Anopheles stephensi, a major vector for malaria parasite transmission, responds
      to Plasmodium infection by synthesis of inflammatory levels of nitric oxide (NO),
      which can limit parasite development in the midgut. We have previously shown that
      Plasmodium falciparum glycosylphosphatidylinositols (PfGPIs) can induce A.
      stephensi NO synthase (AsNOS) expression in the midgut epithelium in vivo in a
      manner similar to the manner in which cytokines and NO are induced by PfGPIs in
      mammalian cells. In mosquito cells, signaling by PfGPIs and P. falciparum
      merozoites is mediated through Akt/protein kinase B (Akt/PKB), the mitogen
      activated protein kinase kinase DSOR1, and extracellular signal-regulated kinase
      (ERK). In mammalian cells, a second parasite factor, malaria pigment or hemozoin
      (Hz), signals NOS induction through ERK- and nuclear factor kappa B-dependent
      pathways and has been demonstrated to be a novel proinflammatory ligand for Toll
      like receptor 9. In this study, we demonstrate that Hz can also induce AsNOS gene
      expression in immortalized A. stephensi and Anopheles gambiae cell lines in vitro
      and in A. stephensi midgut tissue in vivo. In mosquito cells, Hz signaling is
      mediated through transforming growth factor beta-associated kinase 1, Akt/PKB,
      ERK, and atypical protein kinase C zeta/lambda. Our results show that Hz is a
      prominent parasite-derived signal for Anopheles and that signaling pathways
      activated by PfGPIs and Hz have both unique and shared components. Together with
      our previous findings, our data indicate that parasite signaling of innate
      immunity is conserved in mosquito and mammalian cells.

PMID- 17526742
TI  - Adherence-inhibitory intestinal immunoglobulin a antibody response in baboons
      elicited by use of a synthetic intranasal lectin-based amebiasis subunit vaccine.
AB  - We designed an amebiasis subunit vaccine that is constructed by using four
      peptide epitopes of the galactose-inhibitable lectin heavy subunit that were
      recognized by intestinal secretory immunoglobulin A (IgA) antibodies from immune
      human subjects. These epitopes are contained in the region encompassing amino
      acids 758 to 1134 of the lectin heavy subunit, designated LC3. Baboons (Papio
      anubis) are natural hosts for Entamoeba histolytica; naturally infected baboons
      raised in captivity possess serum IgA antibodies to the same four LC3 epitopes as
      humans. Uninfected, seronegative baboons received four intranasal immunizations
      at 7-day intervals with the synthetic peptide vaccine (400, 800, or 1,600 mug per
      nostril) with cholera toxin (20 mug) as the adjuvant. As determined by an enzyme
      linked immunosorbent assay (ELISA), each dose of the peptide vaccine elicited
      antipeptide serum IgA and IgG and intestinal IgA antibody responses in all six
      immunized baboons by day 28, 7 days after the last immunization (P, <0.01 for
      each dose compared to the cholera toxin control). The peptide vaccine elicited
      serum IgG and intestinal IgA antibodies that recognized purified recombinant LC3
      protein (P, <0.008 and 0.02, respectively) and native lectin protein (P < 0.01).
      In addition, an indirect immunofluorescence assay with whole trophozoites (P <
      0.01) and Western blot analysis confirmed that serum IgG antibodies from
      vaccinated baboons recognized native lectin protein on the surfaces of axenic E.
      histolytica trophozoites or from solubilized amebae. All four synthetic peptides
      were immunogenic; the vaccine elicited dose- and time-dependent responses, as
      determined by ELISA optical density readings indicating the production of serum
      and intestinal antibodies (P, <0.02 for antipeptide and antilectin antibodies).
      As a positive control, intranasal immunization with purified recombinant LC3
      protein with cholera toxin as the adjuvant elicited a serum anti-LC3 IgA and IgG
      antibody response (P, 0.05 and <0.0001, respectively); however, no intestinal
      anti-LC3 IgA antibody response was observed (P = 0.4). Of interest, serum IgA and
      IgG antibodies elicited by the recombinant LC3 vaccine did not recognize any of
      the four putatively protective LC3 peptide epitopes. Both serum and fecal
      antibodies elicited by the peptide vaccine exhibited neutralizing activity, as
      determined by their dose-dependent inhibition of the galactose-specific adherence
      of E. histolytica trophozoites to Chinese hamster ovary cells in vitro (P, <0.001
      for each group of antibodies compared to the control). In summary, a lectin-based
      intranasal polylysine-linked synthetic peptide vaccine was effective in eliciting
      an adherence-inhibitory, intestinal antilectin IgA antibody response in baboons.
      Future studies with the baboon model will determine vaccine efficacy against
      asymptomatic E. histolytica intestinal infection.

PMID- 17526743
TI  - Soluble CD14 and CD83 from human neonatal antigen-presenting cells are inducible
      by commensal bacteria and suppress allergen-induced human neonatal Th2
      differentiation.
AB  - CD14 is expressed on the cell surface of various antigen-presenting cells, and
      CD83 is a maturation marker for dendritic cells (DC). CD14 and CD83 are also
      present as soluble proteins, and both have immunoregulatory functions. We
      examined whether neonatal cord blood monocytes or DC released soluble CD14
      (sCD14) or sCD83 when exposed to the commensal intestinal bacteria Clostridium
      perfringens, Staphylococcus aureus, Lactobacillus rhamnosus, Escherichia coli,
      and Bacteroides fragilis. We found that the gram-positive bacteria C. perfringens
      and S. aureus, but not gram-negative bacteria, induced the release of sCD14 from
      monocytes. DC, on the other hand, released sCD14 in response to both gram
      positive and gram-negative bacteria. Moreover, the expression of the virulence
      factor staphylococcal protein A seemed to be important for S. aureus-induced
      sCD14 production from both monocytes and DC. Soluble CD83 was released from DC,
      but not from monocytes, when exposed to both gram-positive and gram-negative
      bacteria. Finally, to investigate whether sCD14 or sCD83 could modulate neonatal
      allergen-induced T-cell differentiation, DC were exposed to birch allergen alone
      or in the presence of sCD14 or sCD83 and then cocultured with autologous T cells.
      We demonstrate that sCD14 and sCD83 inhibited the birch allergen-induced Th2
      differentiation by suppressing interleukin 13 production. Together, these results
      suggest that the commensal intestinal flora may be an important stimulus for the
      developing immune system by inducing the immunoregulatory proteins sCD14 and
      sCD83, which may be involved in preventing T-cell sensitization to allergens in
      infants.

PMID- 17526744
TI  - Heptose I glycan substitutions on Neisseria gonorrhoeae lipooligosaccharide
      influence C4b-binding protein binding and serum resistance.
AB  - Lipooligosaccharide (LOS) heptose (Hep) glycan substitutions influence gonococcal
      serum resistance. Several gonococcal strains bind the classical complement
      pathway inhibitor, C4b-binding protein (C4BP), via their porin (Por) molecule to
      escape complement-dependent killing by normal human serum (NHS). We show that the
      proximal glucose (Glc) on HepI is required for C4BP binding to Por1B-bearing
      gonococcal strains MS11 and 1291 but not to FA19 (Por1A). The presence of only
      the proximal Glc on HepI (lgtE mutant) permitted maximal C4BP binding to MS11 but
      not to 1291. Replacing 1291 lgtE Por with MS11 Por increased C4BP binding to
      levels that paralleled MS11 lgtE, suggesting that replacement of the Por1B
      molecule dictated the effects of HepI glycans on C4BP binding. The remainder of
      the strain background did not affect C4BP binding; replacing the Por of strain
      F62 with MS11 Por (F62 PorMS11) and truncating HepI mirrored the findings in the
      MS11 background. C4BP binding correlated with resistance to killing by NHS in
      most instances. F62 PorMS11 and its lgtE mutant were sensitive to NHS despite
      binding C4BP, secondary to kinetically overwhelming classical pathway activation
      and possibly increased alternative pathway activation (measured by factor Bb
      binding) by the F62 background. FA19 lgtF (HepI unsubstituted) resisted killing
      by only 10% NHS, not 50% NHS, despite binding levels of C4BP similar to those of
      FA19 and FA19 lgtE (both resistant to 50% serum), suggesting a role for the
      proximal Glc in serum resistance independently of C4BP binding. This study
      provides mechanistic insights into how HepI LOS substitutions affect the serum
      resistance of N. gonorrhoeae.

PMID- 17526745
TI  - Sequential chemotactic and phagocytic activation of human polymorphonuclear
      neutrophils.
AB  - Human polymorphonuclear neutrophils (PMN) chemotax to a foreign entity. When the
      chemoattractants' origins are reached, specific receptors bind to the invader's
      surface, initiating phagocytosis, phagosome formation, and fusion with granule
      membranes, generating the bactericidal oxidative burst, and releasing lytic
      enzymes, specific peptides, and proteins. We explored the initial signaling
      involved in these functions by observing naive, unprimed PMN in suspension using
      fluorescent indicators of cytoplasmic signals (Delta[Ca(2+)](i) and DeltapH(i))
      and of bactericidal entities (oxidative species and elastase) exposed to N-formyl
      methionyl-leucyl-phenylalanine (fMLP) and/or multivalent immune complexes (IC).
      fMLP and IC each initiate a rapid transient rise in [Ca(2+)](i), mostly from
      intracellular stores, simultaneously with a drop in pH(i); these are followed by
      a drop in [Ca(2+)](i) and a rise in pH(i), with the latter being due to a
      Na(+)/H(+) antiport. The impact of a second stimulation depends on the order in
      which stimuli are applied, on their dose, and on their nature. Provided that
      [Ca(2+)](i) is restored, 10(-7) M fMLP, previously shown to elicit maximal
      Delta[Ca(2+)](i) but no bactericidal functions, did not prevent the cells'
      responses with Delta[Ca(2+)](i) to a subsequent high dose of fMLP or IC;
      conversely, cells first exposed to 120 mug/ml IC, previously shown to elicit
      maximal Delta[Ca(2+)](i) and bactericidal functions, exhibited no subsequent
      Delta[Ca(2+)](i) or DeltapH(i) to either stimulus. While exposure to 10(-7) M
      fMLP, which saturates the PMN high-affinity receptor, did not elicit bactericidal
      release from these naive unprimed PMN in suspension, 10(-5) M fMLP did,
      presumably via the low-affinity receptor, using a different Ca(2+) source.

PMID- 17526746
TI  - Nitrate sensing and metabolism modulate motility, biofilm formation, and
      virulence in Pseudomonas aeruginosa.
AB  - Infection by the bacterial opportunist Pseudomonas aeruginosa frequently assumes
      the form of a biofilm, requiring motility for biofilm formation and dispersal and
      an ability to grow in nutrient- and oxygen-limited environments. Anaerobic growth
      by P. aeruginosa is accomplished through the denitrification enzyme pathway that
      catalyzes the sequential reduction of nitrate to nitrogen gas. Mutants mutated in
      the two-component nitrate sensor-response regulator and in membrane nitrate
      reductase displayed altered motility and biofilm formation compared to wild-type
      P. aeruginosa PAO1. Analysis of additional nitrate dissimilation mutants
      demonstrated a second level of regulation in P. aeruginosa motility that is
      independent of nitrate sensor-response regulator function and is associated with
      nitric oxide production. Because motility and biofilm formation are important for
      P. aeruginosa pathogenicity, we examined the virulence of selected regulatory and
      structural gene mutants in the surrogate model host Caenorhabditis elegans.
      Interestingly, the membrane nitrate reductase mutant was avirulent in C. elegans,
      while nitrate sensor-response regulator mutants were fully virulent. The data
      demonstrate that nitrate sensing, response regulation, and metabolism are linked
      directly to factors important in P. aeruginosa pathogenesis.

PMID- 17526747
TI  - Protective immune responses to a recombinant adenovirus type 35 tuberculosis
      vaccine in two mouse strains: CD4 and CD8 T-cell epitope mapping and role of
      gamma interferon.
AB  - There is an urgent need for an efficacious vaccine against tuberculosis (TB).
      Cellular immune responses are key to an effective protective response against TB.
      Recombinant adenovirus (rAd) vectors are especially suited to the induction of
      strong T-cell immunity and thus represent promising vaccine vehicles for the
      prevention of TB. We have previously reported on rAd vector serotype 35, the
      serotype of choice due to low preexisting immunity worldwide, which expresses a
      unique fusion protein of Mycobacterium tuberculosis antigens Ag85A, Ag85B, and
      TB10.4 (Ad35-TBS). Here, we demonstrate that Ad35-TBS confers protection against
      M. tuberculosis when administered to mice through either an intranasal or an
      intramuscular route. Histological evaluation of lung tissue corroborated the
      protection and, in addition, demonstrated differences between two mouse strains,
      with diffuse inflammation in BALB/c mice and distinct granuloma formation in
      C57BL/6 mice. Epitope mapping analysis in these mouse strains showed that the
      major T-cell epitopes are conserved in the artificial fusion protein, while three
      novel CD8 peptides were discovered. Using a defined set of T-cell epitopes, we
      reveal differences between the two mouse strains in the type of protective immune
      response, demonstrating that different antigen-specific gamma interferon (IFN
      gamma)-producing T cells can provide protection against M. tuberculosis
      challenge. While in BALB/c (H-2(d)) mice, a dominant CD8 T-cell response was
      detected, in C57BL/6 (H-2(b)) mice, more balanced CD4/CD8 T-cell responses were
      observed, with a more pronounced CD4 response in the lungs. These results unify
      conflicting reports on the relative importance of CD4 versus CD8 T-cell responses
      in protection and emphasize the key role of IFN-gamma.

PMID- 17526748
TI  - Transcriptome analysis of murine macrophages in response to infection with
      Streptococcus pyogenes reveals an unusual activation program.
AB  - The complex response of murine macrophages to infection with Streptococcus
      pyogenes was investigated at the level of gene expression with a high-density
      oligomer microarray. More than 400 genes were identified as being differentially
      regulated. Many of the up-regulated genes encode molecules involved in the immune
      response and in inflammation, transcription, signaling, apoptosis, the cell
      cycle, electron transport, and cell adhesion. Of particular interest was the up
      regulation of proinflammatory cytokines, typical of the classically activated
      macrophages (M1 phenotype), such as tumor necrosis factor alpha, interleukin 1
      (IL-1), and IL-6, and as well as the up-regulation of anti-inflammatory
      mediators, such as IL-1 decoy receptor and IL-10, associated with alternative
      macrophage activation (M2 phenotype). Furthermore, the gene encoding inducible
      nitric oxide synthase (iNOS), an enzyme typically implicated in classical
      activation, was not induced in infected macrophages. Instead, the gene encoding
      arginase, a competitor for the iNOS substrate arginine involved in the
      alternative activation pathway, was up-regulated in S. pyogenes-infected cells.
      Thus, the microarray-based gene expression analysis demonstrated that S. pyogenes
      induces an atypical activation program in macrophages, with some but not all
      features of the classical or alternative activation phenotypes. The microarray
      data also suggested that the bactericidal activity of macrophages against S.
      pyogenes is mediated by phagocyte oxidase, as p47phox was up-regulated in
      infected cells. Indeed, the in vivo and in vitro killing of S. pyogenes was
      markedly diminished in the absence of functional phagocyte (p47(phox-/-)) but not
      in the absence of iNOS (iNOS(-/-)). An understanding of how macrophages respond
      to S. pyogenes at the molecular level may facilitate the development of new
      therapeutic paradigms.

PMID- 17526749
TI  - An SNF2 protein associated with nuclear RNA silencing and the spread of a
      silencing signal between cells in Arabidopsis.
AB  - The silencing phenotype in Arabidopsis thaliana lines with an inverted repeat
      transgene under the control of a phloem-specific promoter was manifested in
      regions around veins due to a mobile signal of silencing. Genetic analysis
      implicates RNA-DEPENDENT RNA POLYMERASE2 (RDR2) and an RNA polymerase IVa subunit
      gene (NRPD1a) in the signaling mechanism. We also identified an SNF2 domain
      containing protein (CLASSY1) that acts together with RDR2 and NRPD1a in the
      spread of transgene silencing and in the production of endogenous 24-nucleotide
      short interfering RNAs (siRNAs). Cytochemical analysis indicates that CLASSY1 may
      act in the nucleus with NRPD1a and RDR2 in the upstream part of RNA silencing
      pathways that generate a double-stranded RNA substrate for Dicer-like (DCL)
      nucleases. DCL3 and ARGONAUTE4 act in a downstream part of the pathway, leading
      to endogenous 24-nucleotide siRNA production, but are not required for
      intercellular signaling. From genetic analysis, we conclude that another
      downstream part of the pathway associated with intercellular signaling requires
      DCL4 and at least one other protein required for 21-nucleotide trans-acting
      siRNAs. We interpret the effect of polymerase IVa and trans-acting siRNA pathway
      mutations in terms of a modular property of RNA silencing pathways.

PMID- 17526750
TI  - Physical association of the NB-LRR resistance protein Rx with a Ran GTPase
      activating protein is required for extreme resistance to Potato virus X.
AB  - Nucleotide binding leucine-rich repeat (NB-LRR) proteins play an important role
      in plant and mammalian innate immunity. In plants, these resistance proteins
      recognize specific pathogen-derived effector proteins. Recognition subsequently
      triggers a rapid and efficient defense response often associated with the
      hypersensitive response and other poorly understood processes that suppress the
      pathogen. To investigate mechanisms associated with the activation of disease
      resistance responses, we investigated proteins binding to the potato (Solanum
      tuberosum) NB-LRR protein Rx that confers extreme resistance to Potato virus X
      (PVX) in potato and Nicotiana benthamiana. By affinity purification experiments,
      we identified an endogenous N. benthamiana Ran GTPase-Activating Protein2
      (RanGAP2) as an Rx-associated protein in vivo. Further characterization confirmed
      the specificity of this interaction and showed that the association occurs
      through their N-terminal domains. By specific virus-induced gene silencing of
      RanGAP2 in N. benthamiana carrying Rx, we demonstrated that this interaction is
      required for extreme resistance to PVX and suggest that RanGAP2 is part of the Rx
      signaling complex. These results implicate RanGAP-mediated cellular mechanisms,
      including nucleocytoplasmic trafficking, in the activation of disease resistance.

PMID- 17526754
TI  - Changes in qnr prevalence and fluoroquinolone resistance in clinical isolates of
      Klebsiella pneumoniae and Enterobacter spp. collected from 1990 to 2005.
AB  - Clinical isolates of Klebsiella pneumoniae and Enterobacter spp. collected from
      1990 through 2005 at a tertiary care center were studied for qnr genes. Isolates
      bearing these genes emerged in the mid-1990s, coinciding with the time of a rapid
      increase in fluoroquinolone resistance. Sixty percent of these isolates were
      ciprofloxacin susceptible by CLSI breakpoints.

PMID- 17526751
TI  - Structure and function of a mitochondrial late embryogenesis abundant protein are
      revealed by desiccation.
AB  - Few organisms are able to withstand desiccation stress; however, desiccation
      tolerance is widespread among plant seeds. Survival without water relies on an
      array of mechanisms, including the accumulation of stress proteins such as the
      late embryogenesis abundant (LEA) proteins. These hydrophilic proteins are
      prominent in plant seeds but also found in desiccation-tolerant organisms. In
      spite of many theories and observations, LEA protein function remains unclear.
      Here, we show that LEAM, a mitochondrial LEA protein expressed in seeds, is a
      natively unfolded protein, which reversibly folds into alpha-helices upon
      desiccation. Structural modeling revealed an analogy with class A amphipathic
      helices of apolipoproteins that coat low-density lipoprotein particles in
      mammals. LEAM appears spontaneously modified by deamidation and oxidation of
      several residues that contribute to its structural features. LEAM interacts with
      membranes in the dry state and protects liposomes subjected to drying. The
      overall results provide strong evidence that LEAM protects the inner
      mitochondrial membrane during desiccation. According to sequence analyses of
      several homologous proteins from various desiccation-tolerant organisms, a
      similar protection mechanism likely acts with other types of cellular membranes.

PMID- 17526755
TI  - Deoxyribonucleoside kinases activate nucleoside antibiotics in severely
      pathogenic bacteria.
AB  - Common bacterial pathogens are becoming progressively more resistant to
      traditional antibiotics, representing a major public-health crisis. Therefore,
      there is a need for a variety of antibiotics with alternative modes of action. In
      our study, several nucleoside analogs were tested against pathogenic
      staphylococci and streptococci. We show that pyrimidine-based nucleoside analogs,
      like 3'-azido-3'-deoxythymidine (AZT) and 2',2'-difluoro-2'deoxycytidine
      (gemcitabine), are specifically activated by the endogenous bacterial
      deoxyribonucleoside kinases, leading to cell death. Deoxyribonucleoside kinase
      deficient Escherichia coli strains become highly susceptible to nucleoside
      analogs when they express recombinant kinases from Staphylococcus aureus or
      Streptococcus pyogenes. We further demonstrate that recombinant S. aureus
      deoxyadenosine kinase efficiently phosphorylates the anticancer drug gemcitabine
      in vitro and is therefore the key enzyme in the activation pathway. When adult
      mice were infected intraperitoneally with a fatal dose of S. pyogenes strain AP1
      and afterwards received gemcitabine, they failed to develop a systemic infection.
      Nucleoside analogs may therefore represent a promising alternative for combating
      pathogenic bacteria.

PMID- 17526756
TI  - Sequencing and comparative genomic analysis of pK29, a 269-kilobase conjugative
      plasmid encoding CMY-8 and CTX-M-3 beta-lactamases in Klebsiella pneumoniae.
AB  - A 269-kilobase conjugative plasmid, pK29, from a Klebsiella pneumoniae strain was
      sequenced. The plasmid harbors multiple antimicrobial resistance genes, including
      those encoding CMY-8 AmpC-type and CTX-M-3 extended-spectrum beta-lactamases in
      the common backbone of IncHI2 plasmids. Mechanisms for dissemination of the
      resistance genes are highlighted in comparative genomic analyses.

PMID- 17526757
TI  - SB-431542, a transforming growth factor beta inhibitor, impairs Trypanosoma cruzi
      infection in cardiomyocytes and parasite cycle completion.
AB  - The antiinflammatory cytokine transforming growth factor beta (TGF-beta) plays an
      important role in Chagas disease, a parasitic infection caused by the protozoan
      Trypanosoma cruzi. In the present study, we show that SB-431542, an inhibitor of
      the TGF-beta type I receptor (ALK5), inhibits T. cruzi-induced activation of the
      TGF-beta pathway in epithelial cells and in cardiomyocytes. Further, we
      demonstrate that addition of SB-431542 greatly reduces cardiomyocyte invasion by
      T. cruzi. Finally, SB-431542 treatment significantly reduces the number of
      parasites per infected cell and trypomastigote differentiation and release. Taken
      together, these data further confirm the major role of the TGF-beta signaling
      pathway in both T. cruzi infection and T. cruzi cell cycle completion. Our
      present data demonstrate that small inhibitors of the TGF-beta signaling pathway
      might be potential pharmacological tools for the treatment of Chagas disease.

PMID- 17526758
TI  - Chloramphenicol is a substrate for a novel nitroreductase pathway in Haemophilus
      influenzae.
AB  - The p-nitroaromatic antibiotic chloramphenicol has been used extensively to treat
      life-threatening infections due to Haemophilus influenzae and Neisseria
      meningitidis; its mechanism of action is the inhibition of protein synthesis. We
      found that during incubation with H. influenzae cells and lysates,
      chloramphenicol is converted to a 4-aminophenyl allylic alcohol that lacks
      antibacterial activity. The allylic alcohol moiety undergoes facile re-addition
      of water to restore the 1,3-diol, as well as further dehydration driven by the
      aromatic amine to form the iminoquinone. Several Neisseria species and most
      chloramphenicol-susceptible Haemophilus species, but not Escherichia coli or
      other gram-negative or gram-positive bacteria we examined, were also found to
      metabolize chloramphenicol. The products of chloramphenicol metabolism by species
      other than H. influenzae have not yet been characterized. The strains reducing
      the antibiotic were chloramphenicol susceptible, indicating that the pathway does
      not appear to mediate chloramphenicol resistance. The role of this novel
      nitroreductase pathway in the physiology of H. influenzae and Neisseria species
      is unknown. Further understanding of the H. influenzae chloramphenicol reduction
      pathway will contribute to our knowledge of the diversity of prokaryotic
      nitroreductase mechanisms.

PMID- 17526759
TI  - Rifaximin does not induce toxin production or phage-mediated lysis of Shiga toxin
      producing Escherichia coli.
AB  - Diarrhea in children is often caused by enteropathogen infections that might
      benefit from early empirical antibiotic therapy. However, when the definition of
      the pathogen requires sophisticated laboratory studies, the etiology of enteritis
      is not known early in illness. Empirical therapy may be dangerous if the child is
      infected with a Shiga toxin-producing Escherichia coli (STEC) strain because
      antimicrobials may increase Shiga toxin (Stx) release, resulting in increased
      risk of microangiopathic hemolytic anemia with acute renal failure (hemolytic
      uremic syndrome [HUS]) and death. There is a need for antimicrobials that would
      be effective against multiple bacterial enteropathogens yet not induce Stx
      release or increase the risk of HUS. Rifaximin has been evaluated in adults for
      treatment of bacterial enteritis and has a good record for safety and efficacy,
      but it has not been evaluated extensively in children with gastroenteritis. We
      therefore evaluated rifaximin's potential for phage induction, drug-induced
      bacteriolysis, and toxin release in 57 STEC strains (26 O157 and 31 non-O157
      strains). Growth in ciprofloxacin, a known Stx phage inducer, caused
      bacteriolysis and release of toxin in 25/26 (96%) O157 strains and 15/31 (48%)
      non-O157 strains. In contrast, rifaximin did not induce phage replication or
      lysis in any strain. Toxin release in the presence of rifaximin was not different
      from release in the absence of antibiotic. Rifaximin, unlike many antibiotics
      used to treat pediatric gastroenteritis, does not induce phage-mediated
      bacteriolysis and Stx release.

PMID- 17526760
TI  - Promising clinical efficacy of streptomycin-rifampin combination for treatment of
      buruli ulcer (Mycobacterium ulcerans disease).
AB  - According to recommendations of the 6th WHO Advisory Committee on Buruli ulcer,
      directly observed treatment with the combination of rifampin and streptomycin,
      administered daily for 8 weeks, was recommended to 310 patients diagnosed with
      Buruli ulcer in Pobe, Benin. Among the 224 (72%) eligible patients for whom
      treatment was initiated, 215 (96%) were categorized as treatment successes, and
      9, including 1 death and 8 losses to follow-up, were treatment failures. Of the
      215 successfully treated patients, 102 (47%) were treated exclusively with
      antibiotics and 113 (53%) were treated with antibiotics plus surgical excision
      and skin grafting. The size of lesions at treatment initiation was the major
      factor associated with surgical intervention: 73% of patients with lesions of >15
      cm in diameter underwent surgery, whereas only 17% of patients with lesions of <5
      cm had surgery. No patient discontinued therapy for side effects from the
      antibiotic treatment. One year after stopping treatment, 208 of the 215 patients
      were actively retrieved to assess the long-term therapeutic results: 3 (1.44%) of
      the 208 retrieved patients had recurrence of Mycobacterium ulcerans disease, 2
      among the 107 patients treated only with antibiotics and 1 among the 108 patients
      treated with antibiotics plus surgery. We conclude that the WHO-recommended
      streptomycin-rifampin combination is highly efficacious for treating M. ulcerans
      disease. Chemotherapy alone was successful in achieving cure in 47% of cases and
      was particularly effective against ulcers of less than 5 cm in diameter.

PMID- 17526761
TI  - Ulnar deep venous thrombosis in a professional baseball pitcher: a case report.

PMID- 17526762
TI  - Translational research: advancing medical science by stimulating
      interdisciplinary research.

PMID- 17526763
TI  - Purinoceptors in the kidney.
AB  - The multiple roles of extracellular ATP and its metabolite adenosine include
      broad areas, such as regulating vascular tone and inducing inflammation. This
      review will discuss purinoceptor-induced effects on renal vascular resistance,
      highlighting the key experiments providing a significant contribution to our
      current understanding of autoregulatory mechanisms. Emphasis will be placed on
      the purinoceptor subtypes involved in autoregulatory control by ATP and
      adenosine. Additionally, the role of purinoceptors in hypertension-associated
      impairment of autoregulatory efficiency will be discussed.

PMID- 17526764
TI  - Adipokines and coronary vasomotor dysfunction.
AB  - Research in the last 10-15 years has shown that fat cells (adipocytes) produce
      and release proteins with specific biologic activities. These proteins, termed
      adipokines, include the hormones leptin, adiponectin, and resistin. Adipose
      tissue is now recognized as an active endocrine organ. With the obesity pandemic
      swelling in the Western world, ongoing research is aimed at determining the
      biologic links between obesity and cardiovascular disease. This review presents
      basic historical background information on the major adipokines, introduces
      findings from clinical studies associating adipokines with cardiovascular
      disease, and summarizes results from recent basic science research studies of
      mechanisms of adipokine-induced cardiovascular dysfunction. Particular emphasis
      is placed on the action of adipokines in the coronary circulation-especially
      effects of adipokines on endothelial function, as endothelial damage is likely a
      critical event initiating atherosclerotic coronary artery disease.

PMID- 17526765
TI  - ICAM-1 and CD11b/CD18 expression during acute pancreatitis induced by bile
      pancreatic duct obstruction: effect of N-acetylcysteine.
AB  - Different molecules are involved in the recruitment of leukocytes during
      inflammation. The aim was to investigate (i) the contribution of acinar cells to
      the overall production of ICAM-1 and (ii) the kinetics of leukocyte CD11b/CD18
      expression during acute pancreatitis (AP) induced by bile-pancreatic duct
      obstruction (BPDO) to evaluate the contribution of both molecules to leukocyte
      homing. The role of reactive oxygen species (ROS) as mediators in the expression
      of ICAM-1 and CD11b/CD18 was examined by using N-acetylcysteine (NAC) as an
      antioxidant treatment. By mechanisms resistant to NAC treatment, acinar cells
      were able to produce ICAM-1 at first onset of AP; other cell sources contribute
      to maintaining increased ICAM-1 plasma levels during AP. By contrast, CD11b/CD18
      was overexpressed in leukocytes in the course of AP by oxidant-dependent
      mechanisms. Since NAC treatment reduced neutrophil infiltration in the pancreas,
      we conclude that CD11b/CD18 over-expression is required for leukocyte
      recruitment; however, other adhesion molecules in addition to ICAM-1 seem to
      contribute to leukocyte homing during BPDO-induced AP.

PMID- 17526766
TI  - Lead does not affect transcription of intestinal zinc-binding proteins in growing
      rats.
AB  - Environmental lead exposure remains a serious concern for the growth and
      development of children. Micronutrient status may affect the absorption and
      tissue accumulation of lead, but the mechanisms of gastrointestinal uptake and
      transport remain unknown. Thus, our objective was to investigate the effects of
      lead on the mRNA levels of intestinal zinc transporter 4 (ZIP4), metallothionein
      (MT), cysteine-rich intestinal protein (CRIP), and divalent metal transporter 1
      (DMT1) in growing rats fed marginal, adequate, and supplemental zinc diets.
      Weanling Sprague Dawley rats were assigned to marginal zinc (MZ; 8 mg Zn/kg
      diet), zinc-adequate control (CT; 30 mg Zn/kg), zinc-adequate diet-restricted
      (DR; 30 mg Zn/kg), or supplemental zinc (SZ; 300 mg Zn/kg) groups, with and
      without lead acetate-containing drinking water (200 mg Pb/l) for 3 weeks.
      Duodenum was analyzed for ZIP4, MT, CRIP, and DMT1 mRNA levels by real-time
      reverse transcription-polymerase chain reaction and MT immunolocalization.
      Tissues were analyzed for zinc, lead, and iron by inductively coupled plasma
      spectrometry. MZ rats had higher duodenal ZIP4 mRNA levels, lower MT mRNA levels,
      lower MT immunostaining intensity, and lower zinc concentrations than DR, CT, and
      SZ. Duodenal DMT1 mRNA levels were lower in DR and SZ compared with MZ. Tissue
      lead concentrations responded to dietary zinc with SZ < CT < DR <or= MZ. The
      greater accumulation of hepatic lead in MZ rats was associated with zinc
      deficiency as well as diet restriction. Lead treatment resulted in higher hepatic
      iron concentrations but had no effect on duodenal ZIP4, MT, CRIP, or DMT1 mRNA
      levels. Thus, tissue lead accumulation was not directly mediated by the
      transcriptional induction of zinc and iron binding or transport proteins. The
      mechanisms of lead absorption during nutritional deficiency and supplementation
      require further investigation.

PMID- 17526767
TI  - Interaction of sesame seed and tamoxifen on tumor growth and bone health in
      athymic mice.
AB  - Some premenopausal breast cancer patients use phytoestrogen-rich soy and flaxseed
      to alleviate side effects induced by drugs such as tamoxifen (TAM). Lignan-rich
      flaxseed protects against breast cancer and increases the effectiveness of TAM.
      This study determined the interactive effects of lignan-rich sesame seed (SS) and
      TAM on estrogen-responsive MCF-7 breast tumor growth and bone health in
      ovariectomized athymic mice under premenopausal-simulated conditions.
      Ovariectomized mice with an estrogen implant and established MCF-7 tumors were
      treated for 8 weeks as follows: (i) positive control fed basal diet (BD), (ii) SS
      group fed BD supplemented with 10% ground SS, (iii) TAM group with TAM implant
      fed BD, (iv) SS + TAM group with TAM implant fed BD supplemented with 10% SS, and
      (v) negative control fed BD with no estrogen implant. Palpable tumor data,
      adjusted for body weight, showed that SS does not inhibit MCF-7 tumor growth and
      tends to negate the tumor inhibitory effect of TAM by increasing cell
      proliferation and reducing apoptosis. SS alone and combined with TAM enhanced
      femur biomechanical strength but caused no differences in bone mineral content or
      bone mineral density in either the femur or lumbar vertebrae. SS is not
      protective and interacts adversely with TAM in MCF-7 breast tumors but induces
      beneficial effects on bone both alone and when combined with TAM.

PMID- 17526768
TI  - Androgen regulation of aldehyde dehydrogenase 1A3 (ALDH1A3) in the androgen
      responsive human prostate cancer cell line LNCaP.
AB  - Previous gene array data from our laboratory identified the retinoic acid (RA)
      biosynthesis enzyme aldehyde dehydrogenase 1A3 (ALDH1A3) as a putative androgen
      responsive gene in human prostate cancer epithelial (LNCaP) cells. In the present
      study, we attempted to identify if any of the three ALDH1A/RA synthesis enzymes
      are androgen responsive and how this may affect retinoid-mediated effects in
      LNCaP cells. We demonstrated that exposure of LNCaP cells to the androgen
      dihydrotestosterone (DHT) results in a 4-fold increase in ALDH1A3 mRNA levels
      compared with the untreated control. The mRNA for two other ALDH1A family
      members, ALDH1A1 and ALDH1A2, were not detected and not induced by DHT in LNCaP
      cells. Inhibition of androgen receptor (AR) with both the antiandrogen
      bicalutamide and small interfering RNA for AR support that ALDH1A3 regulation by
      DHT is mediated by AR. Furthermore, specific inhibition of the extracellular
      signal-regulated kinase and Src family of kinases with PD98059 and PP1 supports
      that AR's regulation of ALDH1A3 occurs by the typical AR nuclear-translocation
      cascade. Consistent with an increase in ALDH1A3 mRNA, DHT-treated LNCaP cells
      showed an 8-fold increase in retinaldehyde-dependent NAD(+) reduction compared
      with control. Lastly, treatment of LNCaP with all-trans retinal (RAL) in the
      presence of DHT resulted in significant up-regulation of the RA-inducible, RA
      metabolizing enzyme CYP26A1 mRNA compared with RAL treatment alone. Taken
      together, these data suggest that (i) the RA biosynthesis enzyme ALDH1A3 is
      androgen responsive and (ii) DHT up-regulation of ALDH1A3 can increase the
      oxidation of retinal to RA and indirectly affect RA bioactivity and metabolism.

PMID- 17526769
TI  - Longitudinal ultrastructure study of islet amyloid in the HIP rat model of type 2
      diabetes mellitus.
AB  - In 2004, the human islet amyloid polypeptide (HIP) rat model was created by
      transfecting the Sprague-Dawley rat with the human islet amyloid polypeptide
      (hIAPP)-amylin gene. The objective of this study is to utilize the transmission
      electron microscope to study the longitudinal cellular and extracellular
      morphological changes within the islets of this model at 4, 8, and 14 months of
      age. It has been previously demonstrated that the 2-, 5-, and 10-month HIP models
      have no diabetes, impaired fasting glucose, and diabetes, respectively. The 4
      month HIP model (FBS 123 mg/dl) demonstrated an abundance of beta-cells and
      insulin secretory granules with significant pericapillary and inter-beta-cell
      islet amyloid deposition. The 8-month model (FBS 187 mg/dl) demonstrated
      extensive islet amyloid deposition and marked changes of beta-cell apoptosis. The
      14-month-old model (FBS 244 mg/dl) demonstrated islet and beta-cell atrophy with
      even greater amounts of extracellular islet amyloid compared to the 4-month-old
      and 8-month-old models. Functional beta cells were sparse and were associated
      with intra islet adipose deposition. These findings of ultrastructure cellular
      and extracellular morphological longitudinal remodeling changes in this novel
      animal model of type 2 diabetes may provide investigators with a better
      understanding regarding the role of islet amyloid in human islet.

PMID- 17526770
TI  - Thymic nurse cell multicellular complexes in HY-TCR transgenic mice demonstrate
      their association with MHC restriction.
AB  - This study examines thymic nurse cell (TNC) function during T-cell development.
      It has been suggested that TNCs function in the removal of nonfunctional and/or
      apoptotic thymocytes and do not participate in major histocompatibility complex
      restriction. We analyzed TNCs isolated from both normal C57BL/6 mice and C57BL/6
      TgN (TCRHY) mice (HY-TCR transgenic mice). Using confocal microscopic analyses of
      TNCs isolated from C57BL/6 animals, we showed that 75%-78% of the enclosed
      thymocyte subset was viable, and 87%-90% of these cells expressed both CD4 and
      CD8. CD4 and CD8 also were expressed on TNC thymocytes isolated from both male
      and female HY-TCR transgenic mice. The transgenic female thymus was shown to have
      17 times more TNCs per milligram of thymus than the transgenic male thymus. TNCs
      from HY-TCR transgenic females were 8-10 microm larger than transgenic male TNCs,
      and the female TNCs contained five times more thymocytes within intracytoplasmic
      vacuoles, with less than 4% apoptosis. However, more than 42% of the thymocytes
      within transgenic male TNCs were apoptotic. The large number and size of TNCs
      containing viable thymocytes in the female transgenic thymus suggest that TNC
      function is not limited to the removal of apoptotic thymocytes. We believe that
      the selective uptake of viable double-positive thymocytes by TNCs in C57BL/6 and
      HY-TCR transgenic female mice provides evidence that this interaction occurs
      during the process of major histocompatibility complex restriction.

PMID- 17526771
TI  - The cobalamin precursor cobinamide detoxifies nitroprusside-generated cyanide.
AB  - Sodium nitroprusside is used to treat hypertensive emergencies and acute heart
      failure. It acts by releasing nitric oxide (NO), a highly potent vasodilator, but
      unfortunately, for each NO molecule released, five cyanide ions are released.
      Thus, nitroprusside therapy is limited by cyanide toxicity. Therefore, a cyanide
      scavenger could be beneficial when administering nitroprusside. Hydroxocobalamin,
      which has a relatively high binding affinity for cyanide, has been shown to
      reduce cyanide levels in nitroprusside-treated patients. Cobinamide, the
      penultimate precursor in hydroxocobalamin biosynthesis, has a much greater
      affinity for cyanide than cobalamin, and binds two cyanide ions. We now show that
      cobinamide is highly effective in neutralizing cyanide ions released by
      nitroprusside in cultured mammalian cells, Drosophila melanogaster, and mice.
      Cobinamide also binds NO, but at molar concentrations 2.5-5 times that of
      nitroprusside, it did not decrease NO concentrations or the physiological
      effectiveness of nitroprusside. We conclude that cobinamide could be a valuable
      adjunct to nitroprusside therapy.

PMID- 17526772
TI  - A new role for cathelicidin in ulcerative colitis in mice.
AB  - Cathelicidin, an antimicrobial peptide of the innate immune system, modulates
      microbial growth, wound healing, and inflammation. However, its association with
      inflammatory bowel diseases (IBDs) is unknown. Our objective was to determine
      whether cathelicidin would exert a modulatory effect on the progression of IBD
      and, if so, investigate the mechanism of action through which this effect
      occurred. We evaluated the potential for a synthetic cathelicidin, the mouse
      cathelin-related antimicrobial peptide (mCRAMP), to prevent the initiation and
      promote the healing of lesions from inflammatory colitis that was experimentally
      induced in mice with dextran sulfate sodium (DSS). During the experiment, mCRAMP
      was given: (i) as a parallel treatment starting together with 3% DSS feeding, and
      (ii) as a posttreatment starting 7 days after 3% DSS feeding. The body weight,
      fecal microflora populations, clinical symptoms, and histologic findings of
      colonic tissues were measured. Relative gene expression of mucins (MUC1, MUC2,
      MUC3, and MUC4) in colonic tissues was determined by real-time polymerase chain
      reaction. Intrarectal administration of mCRAMP ameliorated DSS-induced colitis
      with negligible effects on mucosal healing. The peptide also significantly
      reduced the increased number of fecal microflora in colitis animals. It reversed
      the decline of colonic mucus thickness during colitis through upregulation of the
      expression of mucin genes. Treatment with mCRAMP also prevented colitis
      development by suppressing the induction of apoptosis by DSS. The current study
      demonstrates for the first time that intrarectal administration of cathelicidin
      may be a novel therapeutic option for IBDs.

PMID- 17526773
TI  - Adverse effects of rosemary (Rosmarinus officinalis L.) on reproductive function
      in adult male rats.
AB  - Ingestion of rosemary (Rosmarinus officinalis L.) by two groups of adult Sprague
      Dawley rats at levels of 250 and 500 mg/kg body wt for 63 days was investigated
      for its effects on fertility. Body weight and absolute and relative testes
      weights were not affected, but the average weights of epididymides, ventral
      prostates, seminal vesicles, and preputial glands decreased significantly. A
      significant decline in spermatogenesis in testes due to a decrease in the number
      of primary and secondary spermatocytes and spermatids in treatment group 2 (500
      mg/kg) is attributed to a significant decrease in testosterone. Sperm motility
      and density were also significantly decreased in the cauda epididymis and in the
      testes of rosemary-treated male rats in group 2. In addition, the treatment
      markedly increased the number of fetal resorptions in female rats impregnated by
      group 2 males, thereby reducing their fertility.

PMID- 17526774
TI  - Chronic resveratrol enhances endothelium-dependent relaxation but does not alter
      eNOS levels in aorta of spontaneously hypertensive rats.
AB  - Spontaneously hypertensive rats (SHRs) were administered the red wine polyphenol
      resveratrol in drinking water at 0, 0.448, or 4.48 mg/l (control, low, or high,
      respectively) for 28 days. The low dosage was chosen to mimic moderate red wine
      consumption. After the treatment period, thoracic aorta rings were excised for in
      vitro assessment of vasomotor function. Chronic resveratrol significantly
      improved endothelium-dependent relaxation to acetylcholine (Ach), increasing
      maximal values to 80.8% +/- 5.2% and 80.8% +/- 5.0% in low and high groups,
      respectively, compared with 60.7% +/- 1.4% in controls (P<0.01). This treatment
      effect was eliminated in the presence of the endothelial nitric oxide synthase
      (eNOS) blocker N(omega)-nitro-L-arginine methyl ester. Resveratrol did not affect
      relaxation to sodium nitroprusside or systolic blood pressure in SHRs. In
      contrast to the SHR results, chronic resveratrol in Sprague Dawley rats did not
      affect vasomotor function in aorta rings in response to Ach. Hydrogen peroxide
      was reduced in the SHR thoracic aorta by a high dosage of resveratrol (P<0.05),
      but it was not significantly altered in other tissues tested. Thoracic aorta
      immunoblots revealed no significant treatment effects in SHRs on eNOS, superoxide
      dismutases 1 and 2, gp91phox, or Hsp90. Thus, these data provide novel evidence
      of improved endothelium-dependent vasorelaxation in hypertensive, but not
      normotensive, animals as a result of chronic resveratrol consumption mimicking
      dosages resulting from moderate red wine consumption. This response was not
      dependent on increases in eNOS expression but was dependent on improved NO
      bioavailability.

PMID- 17526775
TI  - Dietary polyunsaturated fatty acids alter myocardial protein kinase C expression
      and affect cardioprotection induced by chronic hypoxia.
AB  - We examined the influence of dietary fatty acid (FA) classes on the expression of
      protein kinase C (PKC) delta and epsilon in relation to the cardioprotective
      effects of chronic intermittent hypoxia (CIH). Adult male Wistar rats were fed a
      nonfat diet enriched with 10% lard (saturated FA [SFA]), fish oil (n-3
      polyunsaturated FA [n-3 PUFA]), or corn oil (n-6 PUFA) for 10 weeks. After 4
      weeks on the diet, each group was divided into two subgroups that were either
      exposed to CIH in a barochamber (7000 m, 8 hrs/ day) or kept at normoxia for an
      additional 5-6 weeks. A FA phospholipid profile and Western blot analysis of PKC
      were performed in left ventricles. Infarct size was assessed in anesthetized
      animals subjected to 20-min coronary artery occlusion and 3-hr reperfusion. CIH
      decreased the n-6/n-3 PUFA ratio in all groups by 23% independently of the
      initial value set by various diets. The combination of n-3 diet and CIH had a
      stronger antiarrhythmic effect during reperfusion than the n-3 diet alone; this
      effect was less pronounced in rats fed the n-6 diet. The normoxic n-6 group
      exhibited smaller infarctions (by 22%) than the n-3 group. CIH decreased the
      infarct size in n-3 and SFA groups (by 20% and 23%, respectively) but not in the
      n-6 group. Unlike PKC epsilon, the abundance of PKC delta in the myocardial
      particulate fraction was increased by CIH except for the n-6 group. Myocardial
      infarct size was negatively correlated (r=- 0.79) with the abundance of PKC delta
      in the particulate fraction. We conclude that lipid diets modify the infarct size
      limiting effect of CIH by a mechanism that involves the PKC delta-dependent
      pathway.

PMID- 17526776
TI  - BMP4 promotes formation of primitive vascular networks in human embryonic stem
      cell-derived embryoid bodies.
AB  - The vasculature develops primarily through two processes, vasculogenesis and
      angiogenesis. Although much work has been published on angiogenesis, less is
      known of the mechanisms regulating the de novo formation of the vasculature
      commonly called vasculogenesis. Human embryonic stem cells (hESC) have the
      capability to produce all of the cells of the body and have been used as in vitro
      models to study the molecular signals controlling differentiation and vessel
      assembly. One such regulatory molecule is bone morphogenetic protein-4 (BMP4),
      which is required for mesoderm formation and vascular/hematopoietic specification
      in several species. However, hESC grown in feeder-free conditions and treated
      with BMP4 differentiate into a cellular phenotype highly expressing a trophoblast
      gene profile. Therefore, it is unclear what role, if any, BMP4 plays in
      regulating vascular development in hESC. Here we show in two National Institutes
      of Health-registered hESC lines (BG02 and WA09) cultured on a 3D substrate of
      Matrigel in endothelial cell growth medium-2 that the addition of BMP4 (100
      ng/ml) for 3 days significantly increases the formation and outgrowth of a
      network of cells reminiscent of capillary-like structures formed by mature
      endothelial cells (P<0.05). Analysis of the expression of 45 genes by
      quantitative real time-polymerase chain reaction on a low-density array of the
      entire culture indicates a rapid and significant downregulation of pluripotent
      and most ectodermal markers with a general upregulation of endoderm, mesoderm,
      and endothelial markers. Of the genes assayed, BMPR2 and RUNX1 were
      differentially affected by exposure to BMP4 in both cell lines.
      Immunocytochemistry indicates the morphological structures formed were negative
      for the mature endothelial markers CD31 and CD146 as well as the neural marker
      SOX2, yet positive for the early vascular markers of endothelium (KDR, NESTIN)
      and smooth muscle cells (alpha-smooth muscle actin [alpha SMA]). Together, these
      data suggest BMP4 can enhance the formation and outgrowth of an immature vascular
      system.

PMID- 17526777
TI  - Transcriptome analysis reveals that multidrug efflux genes are upregulated to
      protect Pseudomonas aeruginosa from pentachlorophenol stress.
AB  - Through chemical contamination of natural environments, microbial communities are
      exposed to many different types of chemical stressors; however, research on whole
      genome responses to this contaminant stress is limited. This study examined the
      transcriptome response of a common soil bacterium, Pseudomonas aeruginosa, to the
      common environmental contaminant pentachlorophenol (PCP). Cells were grown in
      chemostats at a low growth rate to obtain substrate-limited, steady-state,
      balanced-growth conditions. The PCP stress was administered as a continuous
      increase in concentration, and samples taken over time were examined for
      physiological function changes with whole-cell acetate uptake rates (WAURs) and
      cell viability and for gene expression changes by Affymetrix GeneChip technology
      and real-time reverse transcriptase PCR. Cell viability, measured by
      heterotrophic plate counts, showed a moderately steady decrease after exposure to
      the stressor, but WAURs did not change in response to PCP. In contrast to the
      physiological data, the microarray data showed significant changes in the
      expression of several genes. In particular, genes coding for multidrug efflux
      pumps, including MexAB-OprM, were strongly upregulated. The upregulation of these
      efflux pumps protected the cells from the potentially toxic effects of PCP,
      allowing the physiological whole-cell function to remain constant.

PMID- 17526778
TI  - Mixed-species biofilm formation by lactic acid bacteria and rice wine yeasts.
AB  - We found that species combinations such as Lactobacillus casei subsp. rhamnosus
      IFO3831 and Saccharomyces cerevisiae Kyokai-10 can form a mixed-species biofilm
      in coculture. Moreover, the Kyokai-10 yeast strain can form a biofilm in
      monoculture in the presence of conditioned medium (CM) from L. casei IFO3831. The
      active substance(s) in bacterial CM is heat sensitive and has a molecular mass of
      between 3 and 5 kDa. In biofilms from cocultures or CM monocultures, yeast cells
      had a distinct morphology, with many hill-like protrusions on the cell surface.

PMID- 17526779
TI  - Comparative sequence analysis of plasmids from Lactobacillus delbrueckii and
      construction of a shuttle cloning vector.
AB  - While plasmids are very commonly associated with the majority of the lactic acid
      bacteria, they are only very rarely associated with Lactobacillus delbrueckii,
      with only four characterized to date. In this study, the complete sequence of a
      native plasmid, pDOJ1, from a strain of Lactobacillus delbrueckii subsp.
      bulgaricus was determined. It consisted of a circular DNA molecule of 6,220 bp
      with a G+C content of 44.6% and a characteristic ori and encoded six open reading
      frames (ORFs), of which functions could be predicted for three-a mobilization
      (Mob) protein, a transposase, and a fused primase-helicase replication protein.
      Comparative analysis of pDOJ1 and the other available L. delbrueckii plasmids
      (pLBB1, pJBL2, pN42, and pLL1212) revealed a very similar organization and amino
      acid identities between 85 and 98% for the putative proteins of all six predicted
      ORFs from pDOJ1, reflecting a common origin for L. delbrueckii plasmids. Analysis
      of the fused primase-helicase replication gene found a similar fused organization
      only in the theta replicating group B plasmids from Streptococcus thermophilus.
      This observation and the ability of the replicon to function in S. thermophilus
      support the idea that the origin of plasmids in L. delbrueckii was likely from S.
      thermophilus. This may reflect the close association of these two species in
      dairy fermentations, particularly yogurt production. As no vector based on
      plasmid replicons from L. delbrueckii has previously been constructed, an
      Escherichia coli-L. delbrueckii shuttle cloning vector, pDOJ4, was constructed
      from pDOJ1, the p15A ori, the chloramphenicol resistance gene of pCI372, and the
      lacZ polylinker from pUC18. This cloning vector was successfully introduced into
      E. coli, L. delbrueckii subsp. bulgaricus, S. thermophilus, and Lactococcus
      lactis. This shuttle cloning vector provides a new tool for molecular analysis of
      Lactobacillus delbrueckii and other lactic acid bacteria.

PMID- 17526781
TI  - "Mark the gene": a method for nondestructive introduction of marker sequences
      inside the gene frame of transgenes.
AB  - A specific marking and detection technique is a fundamental requirement for the
      safer use of genetically modified (GM) organisms. Here we propose a simple and
      effective method for directly marking functional transgenes in GM organisms. For
      that purpose, we introduced nucleotide substitutions (NS), based on the
      degeneracy of codons as markers (NS markers), into the bphC (2,3
      dihydroxybiphenyl dioxygenase) and tomA3 (toluene-ortho-monooxygenase) gene
      frames using a PCR-based method. No change was observed in the enzyme activity of
      translated proteins, and alignments with homologous genes showed the uniqueness
      of the NS markers. Furthermore, we constructed tomA3 variations harboring NS
      markers in different positions. Although the translational products were
      identical, the constructed variation genes could be distinguished through their
      marker patterns by multiplex PCR, showing that NS markers could serve as product
      specific tags for identifying individual GM organisms. This direct method of
      marking the functional transgene provides a simple, low-risk, and robust marking
      method without causing the gene functions to deteriorate.

PMID- 17526780
TI  - Serial analysis of rRNA genes and the unexpected dominance of rare members of
      microbial communities.
AB  - The accurate description of a microbial community is an important first step in
      understanding the roles of its components in ecosystem function. A method for
      surveying microbial communities termed serial analysis of rRNA genes (SARD) is
      described here. Through a series of molecular cloning steps, short DNA sequence
      tags are recovered from the fifth variable (V5) region of the prokaryotic 16S
      rRNA genes from microbial communities. These tags are ligated to form concatemers
      comprised of 20 to 40 tags which are cloned and identified by DNA sequencing.
      Four agricultural soil samples were profiled with SARD to assess the method's
      utility. A total of 37,008 SARD tags comprising 3,127 unique sequences were
      identified. A comparison of duplicate profiles from one soil genomic DNA
      preparation revealed that the method was highly reproducible. The large numbers
      of singleton tags, together with nonparametric richness estimates, indicated that
      a significant amount of sequence tag diversity remained undetected with this
      level of sampling. The abundance classes of the observed tags were scale-free and
      conformed to a power law distribution. Numerically, the majority of the total
      tags observed belonged to abundance classes that were each present at less than
      1% of the community. Over 99% of the unique tags individually made up less than
      1% of the community. Therefore, from either a numerical or diversity standpoint,
      taxa with low abundance comprised a significant proportion of the microbial
      communities examined and could potentially make a large contribution to ecosystem
      function. SARD may provide a means to explore the ecological roles of these rare
      members of microbial communities in qualitative and quantitative terms.

PMID- 17526782
TI  - Monophyly of nodA and nifH genes across Texan and Costa Rican populations of
      Cupriavidus nodule symbionts.
AB  - nodA and nifH phylogenies for Cupriavidus nodule bacteria from native legumes in
      Texas and Costa Rica grouped all strains into a single clade nested among
      neotropical Burkholderia strains. Thus, Cupriavidus symbiotic genes were not
      acquired independently in different regions and are derived from other
      Betaproteobacteria rather than from alpha-rhizobial donors.

PMID- 17526783
TI  - New insights into the colonization and release processes of Xenorhabdus
      nematophila and the morphology and ultrastructure of the bacterial receptacle of
      its nematode host, Steinernema carpocapsae.
AB  - We present results from epifluorescence, differential interference contrast, and
      transmission electron microscopy showing that Xenorhabdus nematophila colonizes a
      receptacle in the anterior intestine of the infective juvenile (IJ) stage of
      Steinernema carpocapsae. This region is connected to the esophagus at the
      esophagointestinal junction. The process by which X. nematophila leaves this
      bacterial receptacle had not been analyzed previously. In this study we monitored
      the movement of green fluorescent protein-labeled bacteria during the release
      process. Our observations revealed that Xenorhabdus colonizes the distal region
      of the receptacle and that exposure to insect hemolymph stimulated forward
      movement of the bacteria to the esophagointestinal junction. Continued exposure
      to hemolymph caused a narrow passage in the distal receptacle to widen, allowing
      movement of Xenorhabdus down the intestine and out the anus. Efficient release of
      both the wild type and a nonmotile strain was evident in most of the IJs
      incubated in hemolymph, whereas only a few IJs incubated in nutrient-rich broth
      released bacterial cells. Incubation of IJs in hemolymph treated with agents that
      induce nematode paralysis dramatically inhibited the release process. These
      results suggest that bacterial motility is not required for movement out of the
      distal region of the receptacle and that hemolymph-induced esophageal pumping
      provides a force for the release of X. nematophila out of the receptacle and into
      the intestinal lumen.

PMID- 17526784
TI  - Mobile genetic elements provide evidence for a bovine origin of clonal complex 17
      of Streptococcus agalactiae.
AB  - We sought an explanation for epidemiological changes in Streptococcus agalactiae
      infections by investigating the link between ecological niches of the bacterium
      by determining the prevalence of 11 mobile genetic elements. The prevalence of
      nine of these elements differed significantly according to the human or bovine
      origin of the isolate. Correlating this distribution with the phylogeny obtained
      by multilocus sequence analysis, we observed that human isolates harboring GBSi1,
      a clear marker of the bovine niche, clustered in clonal complex 17. Our results
      are thus consistent with the emergence of this virulent human clone from a bovine
      ancestor.

PMID- 17526785
TI  - In situ activity and spatial organization of anaerobic ammonium-oxidizing
      (anammox) bacteria in biofilms.
AB  - We investigated autotrophic anaerobic ammonium-oxidizing (anammox) biofilms for
      their spatial organization, community composition, and in situ activities by
      using molecular biological techniques combined with microelectrodes. Results of
      phylogenetic analysis and fluorescence in situ hybridization (FISH) revealed that
      "Brocadia"-like anammox bacteria that hybridized with the Amx820 probe dominated,
      with 60 to 92% of total bacteria in the upper part (<1,000 microm) of the
      biofilm, where high anammox activity was mainly detected with microelectrodes.
      The relative abundance of anammox bacteria decreased along the flow direction of
      the reactor. FISH results also indicated that Nitrosomonas-, Nitrosospira-, and
      Nitrosococcus-like aerobic ammonia-oxidizing bacteria (AOB) and Nitrospira-like
      nitrite-oxidizing bacteria (NOB) coexisted with anammox bacteria and accounted
      for 13 to 21% of total bacteria in the biofilms. Microelectrode measurements at
      three points along the anammox reactor revealed that the NH(4)(+) and NO(2)(-)
      consumption rates decreased from 0.68 and 0.64 micromol cm(-2) h(-1) at P2 (the
      second port, 170 mm from the inlet port) to 0.30 and 0.35 micromol cm(-2) h(-1)
      at P3 (the third port, 205 mm from the inlet port), respectively. No anammox
      activity was detected at P4 (the fourth port, 240 mm from the inlet port), even
      though sufficient amounts of NH(4)(+) and NO(2)(-) and a high abundance of
      anammox bacteria were still present. This result could be explained by the
      inhibitory effect of organic compounds derived from biomass decay and/or produced
      by anammox and coexisting bacteria in the upper parts of the biofilm and in the
      upstream part of the reactor. The anammox activities in the biofilm determined by
      microelectrodes reflected the overall reactor performance. The several groups of
      aerobic AOB lineages, Nitrospira-like NOB, and Betaproteobacteria coexisting in
      the anammox biofilm might consume a trace amount of O(2) or organic compounds,
      which consequently established suitable microenvironments for anammox bacteria.

PMID- 17526786
TI  - Development and application of two multiplex real-time PCR assays for the
      detection of Mycobacterium ulcerans in clinical and environmental samples.
AB  - Mycobacterium ulcerans is a slow-growing environmental bacterium that causes a
      severe skin disease known as Buruli ulcer. PCR has become a reliable and rapid
      method for the diagnosis of M. ulcerans infection in humans and has been used for
      the detection of M. ulcerans in the environment. This paper describes the
      development of a TaqMan assay targeting IS2404 multiplexed with an internal
      positive control to monitor inhibition with a detection limit of less than 1
      genome equivalent of DNA. The assay improves the turnaround time for diagnosis
      and replaces conventional gel-based PCR as the routine method for laboratory
      confirmation of M. ulcerans infection in Victoria, Australia. Following analysis
      of 415 clinical specimens, the new test demonstrated 100% sensitivity and
      specificity compared with culture. Another multiplex TaqMan assay targeting
      IS2606 and the ketoreductase-B domain of the M. ulcerans mycolactone polyketide
      synthase genes was designed to augment the specificity of the IS2404 PCR for the
      analysis of a variety of environmental samples. Assaying for these three targets
      enabled the detection of M. ulcerans DNA in soil, sediment, and mosquito extracts
      collected from an area of endemicity for Buruli ulcer in Victoria with a high
      degree of confidence. Final confirmation was obtained by the detection and
      sequencing of variable-number tandem repeat (VNTR) locus 9, which matched the
      VNTR locus 9 sequence obtained from the clinical isolates in this region. This
      suite of new methods is enabling rapid progress in the understanding of the
      ecology of this important human pathogen.

PMID- 17526787
TI  - SIMPLE approach for isolating mutants expressing fimbriae.
AB  - Genomes of members of the family Enterobacteriaceae contain large repertoires of
      putative fimbrial operons. Since many of these operons are poorly expressed in
      vitro, a convenient method for inducing elaboration of the encoded fimbriae would
      greatly facilitate their functional characterization. Here we describe a new
      technique for identifying fimbriated bacteria from a library of transposon
      mutants by screening with immunomagnetic particles for ligand expression
      (SIMPLE). The SIMPLE method was applied to identify the T-POP mutants of
      Salmonella enterica serotype Typhimurium carrying on their surfaces filaments
      composed of PefA, the major subunit product of a fimbrial operon (pef) that is
      not expressed during growth in Luria-Bertani broth. Four such mutants were
      identified from a library of 24,000 mutants, each of which carried a T-POP
      insertion within the hns gene, which encodes a global silencer of horizontally
      acquired genes. Our data suggest that the SIMPLE method is an effective approach
      for isolating fimbriated bacteria, which can be readily applied to fimbrial
      operons identified by whole-genome sequencing.

PMID- 17526788
TI  - Construction of a low-temperature protein expression system using a cold-adapted
      bacterium, Shewanella sp. strain Ac10, as the host.
AB  - A recombinant protein expression system working at low temperatures is expected
      to be useful for the production of thermolabile proteins. We constructed a low
      temperature expression system using an Antarctic cold-adapted bacterium,
      Shewanella sp. strain Ac10, as the host. We evaluated the promoters for proteins
      abundantly produced at 4 degrees C in this bacterium to express foreign proteins.
      We used 27 promoters and a broad-host-range vector, pJRD215, to produce beta
      lactamase in Shewanella sp. strain Ac10. The maximum yield was obtained when the
      promoter for putative alkyl hydroperoxide reductase (AhpC) was used and the
      recombinant cells were grown to late stationary phase. The yield was 91 mg/liter
      of culture at 4 degrees C and 139 mg/liter of culture at 18 degrees C. We used
      this system to produce putative peptidases, PepF, LAP, and PepQ, and a putative
      glucosidase, BglA, from a psychrophilic bacterium, Desulfotalea psychrophila
      DSM12343. We obtained 48, 7.1, 28, and 5.4 mg/liter of culture of these proteins,
      respectively, in a soluble fraction. The amounts of PepF and PepQ produced by
      this system were greater than those produced by the Escherichia coli T7 promoter
      system.

PMID- 17526789
TI  - Potential interactions of particle-associated anammox bacteria with bacterial and
      archaeal partners in the Namibian upwelling system.
AB  - Recent studies have shown that the anaerobic oxidation of ammonium by anammox
      bacteria plays an important role in catalyzing the loss of nitrogen from marine
      oxygen minimum zones (OMZ). However, in situ oxygen concentrations of up to 25
      microM and ammonium concentrations close to or below the detection limit in the
      layer of anammox activity are hard to reconcile with the current knowledge of the
      physiology of anammox bacteria. We therefore investigated samples from the
      Namibian OMZ by comparative 16S rRNA gene analysis and fluorescence in situ
      hybridization. Our results showed that "Candidatus Scalindua" spp., the typical
      marine anammox bacteria, colonized microscopic particles that were likely the
      remains of either macroscopic marine snow particles or resuspended particles.
      These particles were slightly but significantly (P < 0.01) enriched in
      Gammaproteobacteria (11.8% +/- 5.0%) compared to the free-water phase (8.1% +/-
      1.8%). No preference for the attachment to particles could be observed for
      members of the Alphaproteobacteria and Bacteroidetes, which were abundant (12 to
      17%) in both habitats. The alphaproteobacterial SAR11 clade, the Euryarchaeota,
      and group I Crenarchaeota, were all significantly depleted in particles compared
      to their presence in the free-water phase (16.5% +/- 3.5% versus 2.6% +/- 1.7%,
      2.7% +/- 1.9% versus <1%, and 14.9% +/- 4.6% versus 2.2% +/- 1.8%, respectively,
      all P < 0.001). Sequence analysis of the crenarchaeotal 16S rRNA genes showed a
      99% sequence identity to the nitrifying "Nitrosopumilus maritimus." Even though
      we could not observe conspicuous consortium-like structures of anammox bacteria
      with particle-enriched bacterioplankton groups, we hypothesize that members of
      Gammaproteobacteria, Alphaproteobacteria, and Bacteroidetes play a critical role
      in extending the anammox reaction to nutrient-depleted suboxic water layers in
      the Namibian upwelling system by creating anoxic, nutrient-enriched microniches.

PMID- 17526790
TI  - Nucleotide sequence of plasmid pCNB1 from comamonas strain CNB-1 reveals novel
      genetic organization and evolution for 4-chloronitrobenzene degradation.
AB  - The nucleotide sequence of a new plasmid pCNB1 from Comamonas sp. strain CNB-1
      that degrades 4-chloronitrobenzene (4CNB) was determined. pCNB1 belongs to the
      IncP-1beta group and is 91,181 bp in length. A total of 95 open reading frames
      appear to be involved in (i) the replication, maintenance, and transfer of pCNB1;
      (ii) resistance to arsenate and chromate; and (iii) the degradation of 4CNB. The
      4CNB degradative genes and arsenate resistance genes were located on an
      extraordinarily large transposon (44.5 kb), proposed as TnCNB1. TnCNB1 was
      flanked by two IS1071 elements and represents a new member of the composite I
      transposon family. The 4CNB degradative genes within TnCNB1 were separated by
      various truncated genes and genetic homologs from other DNA molecules. Genes for
      chromate resistance were located on another transposon that was similar to the
      Tn21 transposon of the class II replicative family that is frequently responsible
      for the mobilization of mercury resistance genes. Resistance to arsenate and
      chromate were experimentally confirmed, and transcriptions of arsenate and
      chromate resistance genes were demonstrated by reverse transcription-PCR. These
      results described a new member of the IncP-1beta plasmid family, and the findings
      suggest that gene deletion and acquisition as well as genetic rearrangement of
      DNA molecules happened during the evolution of the 4CNB degradation pathway on
      pCNB1.

PMID- 17526791
TI  - Molecular characterization of potential microcystin-producing cyanobacteria in
      Lake Ontario embayments and nearshore waters.
AB  - The distribution and genotypic variation of potential microcystin (MC) producers
      along the southern and eastern shores of Lake Ontario in 2001 and 2003 were
      examined using a suite of PCR primers. Cyanobacterial, Microcystis sp., and
      Microcystis-specific toxin primer sets identified shoreline distribution of
      cyanobacterial DNA (in 97% of the stations) and MC synthetase genes (in 50% of
      the stations). Sequence analysis of a partial mcyA amplicon targeting
      Microcystis, Anabaena, and Planktothrix species indicated that the Microcystis
      sp. genotype was the dominant MC genotype present and revealed a novel
      Microcystis-like sequence containing a 6-bp insert. Analysis of the same samples
      with genus-specific mcyE primers confirmed that the Microcystis sp. genotype was
      the dominant potential MC producer. Genotype compositions within embayments were
      relatively homogenous compared to those for shoreline and tributary samples. MC
      concentrations along the shoreline exhibited both temporal and spatial
      differences as evidenced by the protein phosphatase inhibition assay, at times
      exceeding the World Health Organization guideline value for drinking water of 1.0
      microg MC-LReq liter(-1). MC genotypes are widespread along the New York State
      shoreline of Lake Ontario, appear to originate nearshore, and can be carried
      through the lake via wind and surface water current patterns.

PMID- 17526792
TI  - Carvacrol induces heat shock protein 60 and inhibits synthesis of flagellin in
      Escherichia coli O157:H7.
AB  - The essential oils of oregano and thyme are active against a number of food-borne
      pathogens, such as Escherichia coli O157:H7. Carvacrol is one of the major
      antibacterial components of these oils, and p-cymene is thought to be its
      precursor in the plant. The effects of carvacrol and p-cymene on protein
      synthesis in E. coli O157:H7 ATCC 43895 cells were investigated. Bacteria were
      grown overnight in Mueller-Hinton broth with a sublethal concentration of
      carvacrol or p-cymene, and their protein compositions were analyzed by sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis and confirmed by Western
      blotting. The presence of 1 mM carvacrol during overnight incubation caused E.
      coli O157:H7 to produce significant amounts of heat shock protein 60 (HSP60)
      (GroEL) (P < 0.05) and inhibited the synthesis of flagellin highly significantly
      (P < 0.001), causing cells to be aflagellate and therefore nonmotile. The amounts
      of HSP70 (DnaK) were not significantly affected. p-Cymene at 1 mM or 10 mM did
      not induce HSP60 or HSP70 in significant amounts and did not have a significant
      effect on flagellar synthesis. Neither carvacrol (0.3, 0.5, 0.8, or 1 mM) nor p
      cymene (0.3, 0.5, or 0.8 mM) treatment of cells in the mid-exponential growth
      phase induced significant amounts of HSP60 or HSP70 within 3 h, although
      numerical increases of HSP60 were observed. Motility decreased with increasing
      concentrations of both compounds, but existing flagella were not shed. This study
      is the first to demonstrate that essential oil components induce HSP60 in
      bacteria and that overnight incubation with carvacrol prevents the development of
      flagella in E. coli O157:H7.

PMID- 17526793
TI  - Enteric virus survival during household laundering and impact of disinfection
      with sodium hypochlorite.
AB  - This study was conducted to determine whether enteric viruses (adenovirus,
      rotavirus, and hepatitis A virus) added to cotton cloth swatches survive the wash
      cycle, the rinse cycle, and a 28-min permanent press drying cycle as commonly
      practiced in households in the United States. Detergent with and without bleach
      (sodium hypochlorite) was added to washing machines containing sterile and virus
      inoculated 58-cm2 swatches, 3.2 kg of cotton T-shirts and underwear, and a soiled
      pillowcase designed to simulate the conditions (pH, organic load, etc.)
      encountered in soiled laundry. The most important factors for the reduction of
      virus in laundry were passage through the drying cycle and the addition of sodium
      hypochlorite. Washing with detergent alone was not found to be effective for the
      removal or inactivation of enteric viruses, as significant concentrations of
      virus were found on the swatches (reductions of 92 to 99%). It was also
      demonstrated that viruses are readily transferred from contaminated cloths to
      uncontaminated clothes. The use of sodium hypochlorite reduced the number of
      infectious viruses on the swatches after washing and drying by at least 99.99%.
      Laundering practices in common use in the United States do not eliminate enteric
      and respiratory viruses from clothes. The use of bleach can further reduce the
      numbers of enteric viruses in laundry.

PMID- 17526794
TI  - Bacteriophage therapy to reduce salmonella colonization of broiler chickens.
AB  - Acute enteric infections caused by salmonellas remain a major public health
      burden worldwide. Poultry, particularly chickens, are known to be the main
      reservoir for this zoonotic pathogen. Although some progress has been made in
      reducing Salmonella colonization of broiler chickens by using biosecurity and
      antimicrobials, it still remains a considerable problem. The use of host-specific
      bacteriophages as a biocontrol is one possible intervention by which Salmonella
      colonization could be reduced. A total of 232 Salmonella bacteriophages were
      isolated from poultry farms, abattoirs, and wastewater in 2004 and 2005. Three
      phages exhibiting the broadest host ranges against Salmonella enterica serotypes
      Enteritidis, Hadar, and Typhimurium were characterized further by determining
      their morphology and lytic activity in vitro. These phages were then administered
      in antacid suspension to birds experimentally colonized with specific Salmonella
      host strains. The first phage reduced S. enterica serotype Enteritidis cecal
      colonization by > or = 4.2 log10 CFU within 24 h compared with controls.
      Administration of the second phage reduced S. enterica serotype Typhimurium by >
      or = 2.19 log10 CFU within 24 h. The third bacteriophage was ineffective at
      reducing S. enterica serotype Hadar colonization. Bacteriophage resistance
      occurred at a frequency commensurate with the titer of phage being administered,
      with larger phage titers resulting in a greater proportion of resistant
      salmonellas. The selection of appropriate bacteriophages and optimization of both
      the timing and method of phage delivery are key factors in the successful phage
      mediated control of salmonellas in broiler chickens.

PMID- 17526795
TI  - Ecological genomics of marine Roseobacters.
AB  - Bacterioplankton of the marine Roseobacter clade have genomes that reflect a
      dynamic environment and diverse interactions with marine plankton. Comparative
      genome sequence analysis of three cultured representatives suggests that cellular
      requirements for nitrogen are largely provided by regenerated ammonium and
      organic compounds (polyamines, allophanate, and urea), while typical sources of
      carbon include amino acids, glyoxylate, and aromatic metabolites. An unexpectedly
      large number of genes are predicted to encode proteins involved in the
      production, degradation, and efflux of toxins and metabolites. A mechanism likely
      involved in cell-to-cell DNA or protein transfer was also discovered: vir-related
      genes encoding a type IV secretion system typical of bacterial pathogens. These
      suggest a potential for interacting with neighboring cells and impacting the
      routing of organic matter into the microbial loop. Genes shared among the three
      roseobacters and also common in nine draft Roseobacter genomes include those for
      carbon monoxide oxidation, dimethylsulfoniopropionate demethylation, and aromatic
      compound degradation. Genes shared with other cultured marine bacteria include
      those for utilizing sodium gradients, transport and metabolism of sulfate, and
      osmoregulation.

PMID- 17526796
TI  - Insertional mutagenesis to generate lantibiotic resistance in Lactococcus lactis.
AB  - While the potential emergence of food spoilage and pathogenic bacteria with
      resistance to lantibiotics is a concern, the creation of derivatives of starter
      cultures and adjuncts that can grow in the presence of these antimicrobials may
      have applications in food fermentations. Here a bank of Lactococcus lactis IL1403
      mutants was created and screened, and a number of novel genetic loci involved in
      lantibiotic resistance were identified.

PMID- 17526797
TI  - A general framework for designing and validating oligomer-based DNA microarrays
      and its application to Clostridium acetobutylicum.
AB  - While DNA microarray analysis is widely accepted as an essential tool for modern
      biology, its use still eludes many researchers for several reasons, especially
      when microarrays are not commercially available. In that case, the design,
      construction, and use of microarrays for a sequenced organism constitute
      substantial, time-consuming, and expensive tasks. Recently, it has become
      possible to construct custom microarrays using industrial manufacturing
      processes, which offer several advantages, including speed of manufacturing,
      quality control, no up-front setup costs, and need-based microarray ordering.
      Here, we describe a strategy for designing and validating DNA microarrays
      manufactured using a commercial process. The 22K microarrays for the solvent
      producer Clostridium acetobutylicum ATCC 824 are based on in situ-synthesized 60
      mers employing the Agilent technology. The strategy involves designing a large
      library of possible oligomer probes for each target (i.e., gene or DNA sequence)
      and experimentally testing and selecting the best probes for each target. The
      degenerate C. acetobutylicum strain M5 lacking the pSOL1 megaplasmid (with 178
      annotated open reading frames [genes]) was used to estimate the level of probe
      cross-hybridization in the new microarrays and to establish the minimum intensity
      for a gene to be considered expressed. Results obtained using this microarray
      design were consistent with previously reported results from spotted cDNA-based
      microarrays. The proposed strategy is applicable to any sequenced organism.

PMID- 17526799
TI  - Correlations between clinical severity, genotype and muscle pathology in limb
      girdle muscular dystrophy type 2A.
AB  - BACKGROUND: Limb girdle muscular dystrophy type 2A (LGMD2A) is characterised by
      wide variability in clinical features and rate of progression. Patients with two
      null mutations usually have a rapid course, but in the remaining cases (two
      missense mutations or compound heterozygote mutations) prognosis is uncertain.
      METHODS: We conducted what is to our knowledge the first systematic
      histopathological, biochemical and molecular investigation of 24 LGMD2A patients,
      subdivided according to rapid or slow disease progression, to determine if some
      parameters could correlate with disease progression. RESULTS: We found that
      muscle histopathology score and the extent of regenerating and degenerating
      fibres could be correlated with the rate of disease course when the biochemical
      and molecular data do not offer sufficient information. Comparison of clinical
      and muscle histopathological data between LGMD2A and four other types of LGMD
      (LGMD2B-E) also gave another important and novel result. We found that LGMD2A has
      significantly lower levels of dystrophic features (ie degenerating and
      regenerating fibres) and higher levels of chronic changes (ie lobulated fibres)
      compared with other LGMDs, particularly LGMD2B. These results might explain the
      observation that atrophic muscle involvement seems to be a clinical feature
      peculiar to LGMD2A patients. CONCLUSIONS: Distinguishing patterns of muscle
      histopathological changes in LGMD2A might reflect the effects of a disease
      specific pathogenetic mechanism and provide clues complementary to genetic data.

PMID- 17526798
TI  - Cargos and genes: insights into vesicular transport from inherited human disease.
AB  - Many cellular functions depend on the correct delivery of proteins to specific
      intracellular destinations. Mutations that alter protein structure and disrupt
      trafficking of the protein (the "cargo") occur in many genetic disorders. In
      addition, an increasing number of disorders have been linked to mutations in the
      genes encoding components of the vesicular transport machinery responsible for
      normal protein trafficking. We review the clinical phenotypes and molecular
      pathology of such inherited "protein-trafficking disorders", which provide
      seminal insights into the molecular mechanisms of protein trafficking. Further
      characterisation of this expanding group of disorders will provide a basis for
      developing new diagnostic techniques and treatment strategies and offer insights
      into the molecular pathology of common multifactorial diseases that have been
      linked to disordered trafficking mechanisms.

PMID- 17526800
TI  - Cowden syndrome and Bannayan Riley Ruvalcaba syndrome represent one condition
      with variable expression and age-related penetrance: results of a clinical study
      of PTEN mutation carriers.
AB  - BACKGROUND: The most commonly reported phenotypes described in patients with PTEN
      mutations are Bannayan-Riley-Ruvalcaba syndrome (BRRS), with childhood onset,
      macrocephaly, lipomas and developmental delay, and Cowden Syndrome (CS), an adult
      onset condition recognised by mucocutaneous signs, with a risk of cancers, in
      particular those of the thyroid and breast. It has been suggested that BRRS and
      CS are the same condition, but the literature continues to separate them and seek
      a genotype-phenotype correlation. OBJECTIVE: To study the clinical features of
      patients with known PTEN mutations and observe any genotype-phenotype
      correlation. METHODS: In total, 42 people (25 probands and 17 non-probands) from
      26 families of all ages with PTEN mutations were recruited through the UK
      clinical genetics services. A full clinical history and examination were
      undertaken. RESULTS: We were unable to demonstrate a genotype-phenotype
      correlation. Furthermore, our findings in a 31-year-old woman with CS and an exon
      1 deletion refutes previous reports that whole exon deletions are only found in
      patients with a BRRS phenotype. CONCLUSION: Careful phenotyping gives further
      support for the suggestion that BRRS and CS are actually one condition,
      presenting variably at different ages, as in other tumour-suppressor disorders
      such as neurofibromatosis type 1. This has important counselling implications,
      such as advice about cancer surveillance, for children diagnosed with BRRS.

PMID- 17526801
TI  - The spectrum of vascular anomalies in patients with PTEN mutations: implications
      for diagnosis and management.
AB  - BACKGROUND: Mutations in the PTEN gene cause two disorders that predispose to
      cancer, Bannayan-Riley-Ruvalcaba and Cowden syndromes. Some patients with a PTEN
      mutation have only macrocephaly and autism, but they may still be at risk for
      neoplasms. Vascular anomalies occur in patients with a PTEN mutation, but they
      have not been systematically studied or precisely defined. METHOD: We analysed
      the clinical and radiological features of the vascular anomalies in 26 patients
      with PTEN mutations who were either seen or had their medical records reviewed at
      Children's Hospital Boston. RESULTS: All 23 patients who had their head
      circumference measured were macrocephalic, and all 13 male patients who were
      fully examined had penile freckling. Vascular anomalies were found in 14/26 (54%)
      of patients: 8/14 (57%) had multiple lesions and 11/13 (85%) who had cross
      sectional imaging had intramuscular vascular lesions. Radiographic studies showed
      that 12/14 (86%) were fast-flow vascular anomalies, and angiography typically
      showed focal segmental dilatation of draining veins. Excessive ectopic fat in the
      vascular anomalies was present in 11/12 (92%) of patients on CT or MRI.
      Intracranial developmental venous anomalies (DVAs) were found in 8/9 (89%) of
      patients who had brain MRI with contrast. CONCLUSIONS: Vascular anomalies in
      patients with a PTEN mutation are typically multifocal intramuscular combinations
      of fast-flow channels and ectopic fat. Cerebral DVAs are very common. PTEN
      mutational analysis should be considered for all macrocephalic patients with fast
      flow vascular anomalies or multiple intracranial DVAs.

PMID- 17526802
TI  - Bone marrow trephine combined with immunohistochemistry is superior to bone
      marrow aspirate in follow-up of myeloma patients.
AB  - AIMS: Multiple myeloma (MM) guidelines in the UK do not advocate performing bone
      marrow trephine biopsy (BMTB) during follow-up. In a recent study, it was found
      that the plasma cell per cent (PC%) in BMTB performed at the time of autologous
      stem cell transplant strongly correlated with survival. The current study
      addresses whether BMTB is superior to bone marrow aspiration (BMA) in documenting
      presence of disease and its volume at follow-up. METHODS: The study involved 106
      samples. A conventional 500-cell differential count was performed on the BMAs to
      document the PC%. The PC% on BMTBs had been estimated on CD138 immunostain.
      Furthermore, BMTBs had also been immunostained for CD56, cyclin D1 and light
      chains. RESULTS: The mean (2SEM) PC% values in BMAs and BMTBs were 13.1 (2.6)%
      and 31.8 (5.8)% respectively. Based on BMA, BMTB and serum/urine paraprotein or
      light chain estimation, on 92 occasions (89%) there was detectable disease. The
      positive predictive value of both BMA and BMTB was 100%, and the negative
      predictive values for BMTB and BMA were 57% and 22% respectively. Among 98
      secretory MM cases, the BMTB-PC% showed significant correlation with paraprotein
      levels, whereas BMA-PC% did not. CONCLUSIONS: It is strongly recommended that
      BMTB is performed and adequately investigated with immunohistochemistry during
      follow-up of MM.

PMID- 17526803
TI  - Detection of the c-kit D816V mutation in systemic mastocytosis by allele-specific
      PCR.
AB  - AIMS: The c-kit D816V activating mutation is found in >80% of cases of systemic
      mastocytosis (SM) and represents a potential drug target. Furthermore, because
      D816V is one of the diagnostic criteria for SM, it is clinically relevant to
      determine whether the mutation is present. Traditional techniques such as DNA
      sequencing are often not sensitive enough to detect mutations in low-abundance
      tumour cells, including SM. Here, an allele-specific assay to detect the D816V
      mutation in DNA from archived formalin-fixed paraffin-embedded tissues is
      described. METHODS: A two-tube PCR format was employed to amplify c-kit exon 17
      as a control and an allele-specific reaction to selectively amplify the D816V
      mutant allele using standard oligonucleotides. A D816V-mutant plasmid control was
      generated by site-directed mutagenesis of wild-type cells. 14 cases of SM, one
      D816V-positive seminoma sample, and 35 cases without SM were analysed using the
      assay. RESULTS: The assay successfully amplified D816V in the mutant plasmid
      control, 13/14 cases of SM, and confirmed D816V in a seminoma sample. In
      addition, D816V was not amplified in 35/35 cases without SM. Serial dilution
      experiments demonstrated sensitivity down to <1%. CONCLUSION: A sensitive,
      specific and cost-effective assay to detect the D816V mutation in archived
      formalin-fixed paraffin-embedded tissues from cases of SM has been developed.

PMID- 17526804
TI  - Chronic atrial fibrillation associated with somatic mitochondrial DNA mutations
      in human atrial tissue.

PMID- 17526805
TI  - Phosphoinositide 3-kinase gamma inhibition plays a crucial role in early steps of
      inflammation by blocking neutrophil recruitment.
AB  - Leukocyte trafficking to inflammatory sites is a gradual process, which is
      dominated in its early phases by chemokine- and cytokine-mediated neutrophil
      recruitment. The chemokine regulated on activation normal T cell expressed and
      secreted (RANTES) has been shown to be highly expressed in the joints of patient
      with rheumatoid arthritis and to promote leukocyte trafficking into the synovial
      tissue. In this study, we investigated the effect of RANTES in a murine model of
      peritoneal chemotaxis, and we found that RANTES dose-dependently induces
      neutrophil recruitment. Then, through morphological and histological analyses, we
      observed that activated neutrophils represent the major infiltrating population
      in response to RANTES chemotactic stimulus. Furthermore, we demonstrated that
      oral administration of either nonisoform-specific phosphoinositide 3-kinase
      (PI3K) inhibitor LY294002 (morpholin-4-yl-8-phenylchromen-4-one) or selective
      PI3Kgamma inhibitor AS041164 (5-benzo[1,3]dioxol-5-ylmethylene-thiazolidine-2,4
      dione) blocks RANTES-induced chemotaxis and reduces the level of AKT
      phosphorylation. Because the two compounds showed a similar pharmacokinetic
      profile in terms of bioavailability and half-life after oral route
      administration, the selective inhibition of the PI3Kgamma-isoform pathway through
      AS041164 was three times more potent in reducing neutrophil recruitment. Finally,
      to confirm the blockade of neutrophil infiltration that occurs in the early phase
      of the inflammatory response, AS041164 was also tested in a model of carrageenan
      induced paw edema in rats. Therefore, the PI3Kgamma pathway plays an important
      role in controlling neutrophil chemotaxis during early steps of inflammation.

PMID- 17526806
TI  - Antiarthritic effects of relaxin, in combination with estrogen, in rat adjuvant
      induced arthritis.
AB  - The incidence and severity of rheumatoid arthritis (RA) are reduced during
      pregnancy. Estradiol-17beta and relaxin (RLX), hormones of pregnancy, are
      implicated in decreased immune responsiveness. The aim of this study was to
      determine the effects of estrogen and RLX, alone or in combination, on the
      development of adjuvant-induced arthritis (AIA) in ovariectomized (OVX) Lewis
      rats. Arthritis was induced on day 0 by adjuvant injection in the left hind paw.
      Rats were treated with estradiol valerate (E), porcine RLX, E + RLX, or vehicle.
      Healthy OVX control animals were used for comparison. Treatment with RLX or E
      alone decreased adjuvant-induced inflammation in both the injected (primary) and
      noninjected (secondary) hind paws. Combined treatment with E and RLX was more
      effective than either hormone alone in blocking secondary paw inflammation.
      Furthermore, E plus RLX reduced changes to spleen and thymus weights induced by
      adjuvant injection. Both E and RLX alone decreased circulating tumor necrosis
      factor (TNF) alpha. The combination of E and RLX resulted in a greater decline in
      TNFalpha than treatment with either hormone alone. There was no effect of
      hormones on the proinflammatory cytokine, interleukin (IL)-1beta. The anti
      inflammatory cytokine IL-10 increased in response to E and E plus RLX. In
      conclusion, combined therapy with E and RLX was more effective than either
      hormone alone in reducing chronic inflammation, joint changes, and high
      circulating TNFalpha associated with AIA in rats. Accordingly, these hormones
      could play a role in reducing RA-induced inflammation during pregnancy by an
      effect on the immune system.

PMID- 17526807
TI  - Galantamine postischemia provides neuroprotection and memory recovery against
      transient global cerebral ischemia in gerbils.
AB  - Galantamine, currently used in Alzheimer's patients, has shown neuroprotection in
      hippocampal slices subjected to oxygenglucose deprivation. Here, we present an in
      vivo study to evaluate the potential neuroprotective effects of galantamine in a
      transient global cerebral ischemia model in gerbils. Three treatment protocols
      were used. In the pretreatment protocol, gerbils were treated before ischemia and
      for 3 consecutive days thereafter. Eight groups of animals were included: sham
      operation plus placebo, 10 mg/kg mecamylamine and 10 mg/kg galantamine,
      respectively; and ischemia plus placebo, 10 mg/kg mecamylamine, 1 mg/kg
      galantamine, and 10 mg/kg galantamine and 10 mg/kg mecamylamine plus galantamine,
      respectively. Postischemia protocols included three groups of animals: sham
      operation, ischemia plus placebo, and ischemia plus 10 mg/kg galantamine;
      substances were administered 3 or 6 h after ischemia and for 2 consecutive days
      thereafter. Pyramidal neurons surviving in the cornus ammonis 1 region of the
      hippocampus were evaluated 72 h after reperfusion, terminal deoxynucleotidyl
      transferase dUTP nick-end labeling (TUNEL) histochemistry, caspase-3 and
      superoxide dismutase (SOD)-2 immunohistochemistries, and Western blottings were
      performed, and object placement tests were carried out. Galantamine significantly
      increased the number of living pyramidal neurons after ischemia-reperfusion
      injury. Galantamine significantly reduced TUNEL, active caspase-3, and SOD-2
      immunoreactivity. The nicotinic antagonist mecamylamine blocked the protective
      effects of galantamine. The neuroprotective effects of galantamine were preserved
      even when first administered at 3 h postischemia. These results correlated with
      the performance in the object placement test. This study shows that galantamine
      provides in vivo neuroprotection and memory recovery against global cerebral
      ischemia, even when administration begins 3 h postischemia.

PMID- 17526808
TI  - High-dose acetaminophen inhibits the lethal effect of doxorubicin in HepG2 cells:
      the role of P-glycoprotein and mitogen-activated protein kinase p44/42 pathway.
AB  - Doxorubicin (DOX) is a widely used chemotherapeutic drug for human hepatocellular
      carcinoma (HCC). A major limitation to its effectiveness is the development of
      multidrug resistance of cancer cells. In clinical trials, patients with advanced
      HCC were treated with high-dose acetaminophen (HAAP) in an effort to improve the
      antitumor activity of chemotherapeutics. In this study, we investigated the
      effect of concomitant treatment of DOX and HAAP on hepatoma-derived HepG2 cells.
      Viability, cell cycle distribution, and ultrastructure were examined.
      Unexpectedly, HAAP, when added to DOX-exposed cells, increased cell viability,
      released cell cycle arrest, and decreased apoptosis. To elucidate the mechanisms
      by which HAAP reduces the DOX lethal effect to HepG2 cells, we investigated the
      multidrug resistance P-glycoprotein (P-gp) and p44/42-mitogen-activated protein
      kinase (MAPK) pathways. The P-gp function was enhanced by DOX and HAAP, and it
      was further stimulated during combined treatment, leading to decreased DOX
      retention. Verapamil (VRP), when added to DOX + HAAP exposure, increased DOX
      accumulation and restored DOX-induced toxicity. The increased phospho-p44/42-MAPK
      level in DOX-exposed cells was inhibited by HAAP. In addition, suppression of
      p44/42 activation by the p44/42-MAPK inhibitor 2'-amino-3'-methoxyflavone
      (PD98059) blocked DOX-induced apoptosis. These findings suggest that the
      antagonistic effect of concomitant DOX + HAAP treatment occurs as a result of
      interactive stimulation of P-gp, generating decreased intracellular drug
      concentrations. Furthermore, inhibition of the p44/42-MAPK phosphorylation by
      HAAP could abolish the DOX-induced cell death pathway. Thus, combined treatment
      by DOX + HAAP, intended to improve chemotherapeutic efficacy, could have an
      opposite effect facilitating cancer cell survival.

PMID- 17526809
TI  - Mice with decreased cerebral dopamine function following a neurotoxic dose of
      MDMA (3,4-methylenedioxymethamphetamine, "Ecstasy") exhibit increased ethanol
      consumption and preference.
AB  - MDMA (3,4-methylenedioxymethamphetamine, "ecstasy") administration to mice
      produces relatively selective long-term neurotoxic damage to dopaminergic
      pathways. There is strong evidence indicating that the dopamine system plays a
      key role in the rewarding effects of ethanol and modulates ethanol intake. Using
      a two-bottle free-choice paradigm, we examined the voluntary consumption and
      preference for ethanol in mice deficient in cerebral dopamine concentration and
      dopamine transporter density by previous repeated MDMA administration. The
      current study shows that mice pre-exposed to a neurotoxic dose of MDMA exhibited
      a higher consumption of and preference for ethanol compared with saline-treated
      animals. The D(1) receptor full agonist SKF81297 [(6-chloro-7,8-dihydroxy-1
      phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrobromide)] attenuated the enhanced
      ethanol intake, an effect that was reversed by SCH23390 [((R)-(+)-7-chloro-8
      hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride], a
      D(1) receptor antagonist. MDMA-exposed mice also showed a reduced release of
      basal dopamine in the nucleus accumbens compared with saline-injected animals and
      a modest increase in D(1) receptor density in caudate-putamen and nucleus
      accumbens. Intraperitoneal administration of ethanol elevated extracellular
      dopamine release in the nucleus accumbens of saline-treated mice, but this effect
      was almost abolished in MDMA-treated mice. Differences between saline- and MDMA
      treated animals did not appear to be secondary to changes in acute ethanol
      clearance. These results indicate that mice with reduced dopamine activity
      following a neurotoxic dose of MDMA exhibit increased ethanol consumption and
      preference and suggest that animals might need to consume more alcohol to reach
      the threshold for the rewarding effects of ethanol.

PMID- 17526810
TI  - Pioglitazone rapidly increases serum adiponectin levels in men with normal
      glucose tolerance.

PMID- 17526811
TI  - Cortisol secretion in patients with type 2 diabetes: relationship with chronic
      complications: response to Chiodini et al.

PMID- 17526813
TI  - Retinopathy predicts cardiovascular mortality in type 2 diabetic men and women:
      response to Juutilainen et al.

PMID- 17526815
TI  - IGF-binding protein-1 levels are related to insulin-mediated glucose disposal and
      are a potential serum marker of insulin resistance: response to Maddux et al.

PMID- 17526817
TI  - Prevalence of nonalcoholic fatty liver disease and its association with
      cardiovascular disease among type 2 diabetic patients: response to Targher et al.
      and Hu et al.

PMID- 17526819
TI  - Primary prevention of cardiovascular diseases in people with diabetes mellitus: a
      scientific statement from the American Heart Association and the American
      Diabetes Association: response to Buse et al.

PMID- 17526821
TI  - Massive weight loss decreases corticosteroid-binding globulin levels and
      increases free cortisol in healthy obese patients: an adaptive phenomenon?
AB  - OBJECTIVE: Obesity, insulin resistance, and weight loss have been associated with
      changes in hypothalamic-pituitary-adrenal (HPA) axis. So far, no conclusive data
      relating to this association are available. In this study, we aim to investigate
      the effects of massive weight loss on cortisol suppressibility, cortisol-binding
      globulin (CBG), and free cortisol index (FCI) in formerly obese women. RESEARCH
      DESIGN AND METHODS: Ten glucose-normotolerant, fertile, obese women (BMI >40
      kg/m2, aged 38.66 +/- 13.35 years) were studied before and 2 years after
      biliopancreatic diversion (BPD) when stable weight was achieved and were compared
      with age-matched healthy volunteers. Cortisol suppression was evaluated by a 4-mg
      intravenous dexamethasone suppression test (DEX-ST). FCI was calculated as the
      cortisol-to-CBG ratio. Insulin sensitivity was measured by an euglycemic
      hyperinsulinemic clamp, and insulin secretion was measured by a C-peptide
      deconvolution method. RESULTS: No difference was found in cortisol suppression
      after DEX-ST before or after weight loss. A decrease in ACTH was significantly
      greater in control subjects than in obese (P = 0.05) and postobese women (P < or
      = 0.01) as was the decrease in dehydroepiandrosterone (P < or = 0.05 and P < or =
      0.01, respectively). CBG decreased from 51.50 +/- 12.76 to 34.33 +/- 7.24 mg/l (P
      < or = 0.01) following BPD. FCI increased from 11.15 +/- 2.85 to 18.16 +/- 6.82
      (P < or = 0.05). Insulin secretion decreased (52.04 +/- 16.71 vs. 30.62 +/- 16.32
      nmol/m(-2); P < or = 0.05), and insulin sensitivity increased by 163% (P < or =
      0.0001). Serum CBG was related to BMI (r(0) = 0.708; P = 0.0001), body weight
      (r(0) = 0.643; P = 0.0001), body fat percent (r(0) = 0.462; P = 0.001), C
      reactive protein (r(0) = 0.619; P = 0.004), and leptin (r(0) = 0.579; P = 0.007)
      and negatively to M value (r(0) = -0.603; P = 0.005). CONCLUSIONS: After massive
      weight loss in morbidly obese subjects, an increase of free cortisol was
      associated with a simultaneous decrease in CBG levels, which might be an adaptive
      phenomenon relating to environmental changes. This topic, not addressed before,
      adds new insight into the complex mechanisms linking HPA activity to obesity.

PMID- 17526822
TI  - National standards for diabetes self-management education.

PMID- 17526823
TI  - Computer modeling of diabetes and its complications: a report on the Fourth Mount
      Hood Challenge Meeting.
AB  - Computer simulation models are mathematical equations combined in a structured
      framework to represent some real or hypothetical system. One of their uses is to
      allow the projection of short-term data from clinical trials to evaluate clinical
      outcomes and costs over a long-term period. This technology is becoming
      increasingly important to assist decision making in modern medicine in situations
      where there is a paucity of long-term clinical trial data, as recently
      acknowledged in the American Diabetes Association Consensus Panel Guidelines for
      Computer Modeling of Diabetes and its Complications. The Mount Hood Challenge
      Meetings provide a forum for computer modelers of diabetes to discuss and compare
      models and identify key areas of future development to advance the field. The
      Fourth Mount Hood Challenge in 2004 was the first meeting of its kind to ask
      modelers to perform simulations of outcomes for patients in published clinical
      trials, allowing comparison against "real life" data. Eight modeling groups
      participated in the challenge. Each group was given three of the following
      challenges: to simulate a trial of type 2 diabetes (CARDS [Collaborative
      Atorvastatin Diabetes Study]); to simulate a trial of type 1 diabetes (DCCT
      [Diabetes Control and Complications Trial]); and to calculate outcomes for a
      hypothetical, precisely specified patient (cross-model validation). The results
      of the models varied from each other and for methodological reasons, in some
      cases, from the published trial data in important ways. This approach of
      performing systematic comparisons and validation exercises has enabled the
      identification of key differences among the models, as well as their possible
      causes and directions for improvement in the future.

PMID- 17526824
TI  - Nonalcoholic fatty liver disease and insulin resistance in youth.

PMID- 17526825
TI  - Thiazolidinedione therapy gets complicated: is bone loss the price of improved
      insulin resistance?

PMID- 17526826
TI  - Aspergillus flavus: human pathogen, allergen and mycotoxin producer.
AB  - Aspergillus infections have grown in importance in the last years. However, most
      of the studies have focused on Aspergillus fumigatus, the most prevalent species
      in the genus. In certain locales and hospitals, Aspergillus flavus is more common
      in air than A. fumigatus, for unclear reasons. After A. fumigatus, A. flavus is
      the second leading cause of invasive aspergillosis and it is the most common
      cause of superficial infection. Experimental invasive infections in mice show A.
      flavus to be 100-fold more virulent than A. fumigatus in terms of inoculum
      required. Particularly common clinical syndromes associated with A. flavus
      include chronic granulomatous sinusitis, keratitis, cutaneous aspergillosis,
      wound infections and osteomyelitis following trauma and inoculation. Outbreaks
      associated with A. flavus appear to be associated with single or closely related
      strains, in contrast to those associated with A. fumigatus. In addition, A.
      flavus produces aflatoxins, the most toxic and potent hepatocarcinogenic natural
      compounds ever characterized. Accurate species identification within Aspergillus
      flavus complex remains difficult due to overlapping morphological and biochemical
      characteristics, and much taxonomic and population genetics work is necessary to
      better understand the species and related species. The flavus complex currently
      includes 23 species or varieties, including two sexual species, Petromyces
      alliaceus and P. albertensis. The genome of the highly related Aspergillus oryzae
      is completed and available; that of A. flavus in the final stages of annotation.
      Our understanding of A. flavus lags far behind that of A. fumigatus. Studies of
      the genomics, taxonomy, population genetics, pathogenicity, allergenicity and
      antifungal susceptibility of A. flavus are all required.

PMID- 17526827
TI  - Phenotypic and functional characterization of Bacillus anthracis biofilms.
AB  - Biofilms, communities of micro-organisms attached to a surface, are responsible
      for many chronic diseases and are often associated with environmental reservoirs
      or lifestyles. Bacillus anthracis is a Gram-positive, endospore-forming bacterium
      and is the aetiological agent of pulmonary, gastrointestinal and cutaneous
      anthrax. Anthrax infections are part of the natural lifecycle of many ruminants
      in North America, including cattle and bison, and B. anthracis is thought to be a
      central part of this ecosystem. However, in endemic areas in which humans and
      livestock interact, chronic cases of cutaneous anthrax are commonly reported.
      This suggests that biofilms of B. anthracis exist in the environment and are part
      of the ecology associated with its lifecycle. Currently, there are few data that
      account for the importance of the biofilm mode of life in B. anthracis, yet
      biofilms have been characterized in other pathogenic and non-pathogenic Bacillus
      species, including Bacillus cereus and Bacillus subtilis, respectively. This
      study investigated the phenotypic and functional role of biofilms in B.
      anthracis. The results demonstrate that B. anthracis readily forms biofilms which
      are inherently resistant to commonly prescribed antibiotics, and that antibiotic
      resistance is not solely the function of sporulation.

PMID- 17526828
TI  - Phase-variable expression of the biofilm-associated protein (Bap) in
      Staphylococcus aureus.
AB  - A process of phase variation is described that affects the expression of Bap
      (biofilm-associated protein) in Staphylococcus aureus. Upon subculture of the Bap
      positive S. aureus strain V329 on Congo red agar, spontaneous smooth biofilm
      negative colonies appeared at a low frequency (5 x 10(-4)). Northern blot
      analysis of these variants with a bap-specific gene probe showed that
      transcription of the bap gene did not occur. However, DNA typing, Southern blot
      hybridization and DNA sequencing did not show any differences between the parent
      V329 strain and the biofilm-negative variants. The biofilm-negative phenotype
      reverted to wild-type at a similar frequency upon subculture of Bap-negative
      variants in liquid media. Experimental infection of ovine mammary glands with Bap
      negative variants showed that phase variation occurred in vivo, because Bap
      expressing, biofilm-positive revertants were isolated from infected mammary
      glands. The absence of Bap correlated with increased adherence to fibrinogen and
      fibronectin. It is possible that S. aureus can detach from a biofilm by switching
      to a Bap-negative state.

PMID- 17526829
TI  - Biofilm exclusion of uropathogenic bacteria by selected asymptomatic bacteriuria
      Escherichia coli strains.
AB  - Many bacterial infections are associated with biofilm formation. In the urinary
      tract bacterial biofilms develop on both living surfaces and artificial implants,
      producing chronic and often intractable infections. Escherichia coli is the most
      common organism associated with urinary tract infections. In contrast to
      uropathogenic E. coli (UPEC), which cause symptomatic urinary tract infection,
      asymptomatic bacteriuria (ABU) strains are associated with essentially symptom
      free infections. Here the biofilm-forming capacity on abiotic surfaces of
      selected E. coli ABU strains and UPEC strains in human urine was investigated. It
      was found that there is a strong bias for biofilm formation by the ABU strains.
      Not only were the ABU strains significantly better biofilm formers than UPEC
      strains, they were also able to out-compete UPEC strains as well as uropathogenic
      strains of Klebsiella spp. during biofilm formation. The results support the
      notion of bacterial prophylaxis employing selected ABU strains to eliminate UPEC
      strains and other pathogens in patients prone to recalcitrant infections.

PMID- 17526830
TI  - Optical maps distinguish individual strains of Escherichia coli O157 : H7.
AB  - Optical maps of 11 Escherichia coli O157 : H7 strains have been generated by the
      assembly of contiguous sets of restriction fragments across their entire 5.3 to
      5.6 Mbp chromosomes. Each strain showed a distinct, highly individual
      configuration of 500-700 BamHI fragments, yielding a map resembling a DNA 'bar
      code'. The accuracy of optical mapping was assessed by comparing directly the in
      silico restriction maps of two wholly sequenced reference genomes of E. coli O157
      : H7, i.e. EDL933 and the Sakai isolate (RIMD 0509952), with the optical maps of
      the same strains. The optical maps of nine other E. coli O157 : H7 strains were
      compared similarly, using the sequence-based maps of the Sakai and EDL933 strains
      as references. A total of 91 changes at 28 loci were positioned and sized; these
      included complex chromosomal inversions, insertions, deletions, substitutions, as
      well as a number of simple RFLPs. The optical maps defined unique genome
      landmarks in each of the strains and demonstrated the ability of optical mapping
      to distinguish and differentiate, at the individual level, strains of this
      important pathogen.

PMID- 17526831
TI  - cAMP signalling is involved in growth, germination, mycoparasitism and secondary
      metabolism in Trichoderma virens.
AB  - An adenylate-cyclase-encoding gene, tac1, of Trichoderma virens, a soil fungus
      used in the biocontrol of plant pathogens, has been cloned and sequenced. The
      tac1 ORF spanned 7032 bp, encoding a protein of 2153 aa, which shared an identity
      of 65 % with the adenylate cyclase of Colletotrichum lagenarium. Deletion of
      tac1, through double-crossover homologous recombination, lowered the
      intracellular cAMP levels to below the detection limit. The mutants showed only 5
      6 % of the wild-type growth rate on agar, but grew normally in shake culture. The
      mutants did not sporulate in darkness, and the spores failed to germinate in
      water. In the confrontation assay, the mutants did not overgrow the test plant
      pathogens Sclerotium rolfsii, Rhizoctonia solani and Pythium sp. Against Pythium
      sp., the mutants produced a clear zone of inhibition in the confrontation assay.
      HPLC analysis and bioassay showed reduced secondary metabolite production in the
      mutants. Using suppression subtractive hybridization (SSH), the genes that were
      underexpressed in the mutants were identified. Based on an array of 53 SSH
      library clones, 11 clones were identified as strongly downregulated in the
      Deltatac1 mutants; of these 11 clones, nine sequences were homologous to
      secondary metabolism-related gene sequences. Therefore, cAMP signalling
      positively regulates secondary metabolism in T. virens. This is believed to be
      the first direct genetic study on the role of cAMP signalling in a Trichoderma
      sp. Tac1 is also believed to be the first regulatory protein to be identified in
      T. virens that is involved in growth, germination, mycoparasitism and secondary
      metabolism.

PMID- 17526832
TI  - TccP2-mediated subversion of actin dynamics by EPEC 2 - a distinct evolutionary
      lineage of enteropathogenic Escherichia coli.
AB  - Enteropathogenic Escherichia coli (EPEC) is a major cause of infantile diarrhoea
      in developing countries. While colonizing the gut mucosa, EPEC triggers extensive
      actin-polymerization activity at the site of intimate bacterial attachment, which
      is mediated by avid interaction between the outer-membrane adhesin intimin and
      the type III secretion system (T3SS) effector Tir. The prevailing dogma is that
      actin polymerization by EPEC is achieved following tyrosine phosphorylation of
      Tir, recruitment of Nck and activation of neuronal Wiskott-Aldrich syndrome
      protein (N-WASP). In closely related enterohaemorrhagic E. coli (EHEC) O157 : H7,
      actin polymerization is triggered following recruitment of the T3SS effector
      TccP/EspF(U) (instead of Nck) and local activation of N-WASP. In addition to
      tccP, typical EHEC O157 : H7 harbour a pseudogene (tccP2). However, it has
      recently been found that atypical, sorbitol-fermenting EHEC O157 carries
      functional tccP and tccP2 alleles. Interestingly, intact tccP2 has been
      identified in the incomplete genome sequence of the prototype EPEC strain B171
      (serotype O111 : H-), but it is missing from another prototype EPEC strain
      E2348/69 (O127 : H7). E2348/69 and B171 belong to two distinct evolutionary
      lineages of EPEC, termed EPEC 1 and EPEC 2, respectively. Here, it is reported
      that while both EPEC 1 and EPEC 2 triggered actin polymerization via the Nck
      pathway, tccP2 was found in 26 of 27 (96.2 %) strains belonging to EPEC 2, and in
      none of the 34 strains belonging to EPEC 1. It was shown that TccP2 was: (i)
      translocated by the locus of enterocyte effacement-encoded T3SS; (ii) localized
      at the tip of the EPEC 2-induced actin-rich pedestals in infected HeLa cells and
      human intestinal in vitro organ cultures ex vivo; and (iii) essential for actin
      polymerization in infected Nck-/- cells. Therefore, unlike strains belonging to
      EPEC 1, strains belonging to EPEC 2 can trigger actin polymerization using both
      Nck and TccP2 actin-polymerization signalling cascades.

PMID- 17526834
TI  - Cloning and characterization of the genes encoding the high-affinity iron-uptake
      protein complex Fet3/Ftr1 in the basidiomycete Phanerochaete chrysosporium.
AB  - MCO1, a multicopper oxidase from Phanerochaete chrysosporium exhibiting strong
      ferroxidase activity, has recently been described. This enzyme shows biochemical
      and structural similarities with the yeast Fet3p, a type I membrane glycoprotein
      that efficiently oxidizes Fe(II) to Fe(III) for its subsequent transport to the
      intracellular compartment by the iron permease Ftr1p. The genome database of P.
      chrysosporium was searched to verify whether it includes a canonical fet3 in
      addition to mco1, and single copies of fet3 and ftr1 orthologues were found,
      separated by a divergent promoter. Pc-fet3 encodes a 628 aa protein that exhibits
      overall identities of about 40 % with other reported Fet3 proteins. In addition
      to a secretion signal, it has a C-terminal transmembrane domain, characteristic
      of these cell-surface-attached ferroxidases. Structural modelling of Pc-Fet3
      revealed that the active site has all the residues known to be essential for
      ferroxidase activity. Pc-ftr1 encodes a 393 aa protein that shows about 38 %
      identity with several Ftr1 proteins from ascomycetes. Northern hybridization
      studies showed that the mRNA levels of both genes are reduced upon
      supplementation of the growth medium with iron, supporting the functional
      coupling of Fet3 and Ftr1 proteins in vivo.

PMID- 17526833
TI  - NsrR: a key regulator circumventing Salmonella enterica serovar Typhimurium
      oxidative and nitrosative stress in vitro and in IFN-gamma-stimulated J774.2
      macrophages.
AB  - Over the past decade, the flavohaemoglobin Hmp has emerged as the most
      significant nitric oxide (NO)-detoxifying protein in many diverse micro
      organisms, particularly pathogenic bacteria. Its expression in enterobacteria is
      dramatically increased on exposure to NO and other agents of nitrosative stress
      as a result of transcriptional regulation of hmp gene expression, mediated by (at
      least) four regulators. One such regulator, NsrR, has recently been shown to be
      responsible for repression of hmp transcription in the absence of NO in
      Escherichia coli and Salmonella, but the roles of other members of this regulon
      in Salmonella, particularly in surviving nitrosative stresses in vitro and in
      vivo, have not been elucidated. This paper demonstrates that an nsrR mutant of
      Salmonella enterica Serovar Typhimurium expresses high levels of Hmp both
      aerobically and anaerobically, exceeding those that can be elicited in vitro by
      supplementing media with S-nitrosoglutathione (GSNO). Elevated transcription of
      ytfE, ygbA, hcp and hcp is also observed, but no evidence was obtained for tehAB
      upregulation. The hyper-resistance to GSNO of an nsrR mutant is attributable
      solely to Hmp, since an nsrR hmp double mutant has a wild-type phenotype.
      However, overexpression of NsrR-regulated genes other than hmp confers some
      resistance of respiratory oxygen consumption to NO. The ability to enhance, by
      mutating NsrR, Hmp levels without recourse to exposure to nitrosative stress was
      used to test the hypothesis that control of Hmp levels is required to avoid
      oxidative stress, Hmp being a potent generator of superoxide. Within IFN-gamma
      stimulated J774.2 macrophages, in which high levels of nitrite accumulated
      (indicative of NO production) an hmp mutant was severely compromised in survival.
      Surprisingly, under these conditions, an nsrR mutant (as well as an nsrR hmp
      double mutant) was also disadvantaged relative to the wild-type bacteria,
      attributable to the combined oxidative effect of the macrophage oxidative burst
      and Hmp-generated superoxide. This explanation is supported by the sensitivity in
      vitro of an nsrR mutant to superoxide and peroxide. Fur has recently been
      confirmed as a weak repressor of hmp transcription, and a fur mutant was also
      compromised for survival within macrophages even in the absence of elevated NO
      levels in non-stimulated macrophages. The results indicate the critical role of
      Hmp in protection of Salmonella from nitrosative stress within and outside
      macrophages, but also the key role of transcriptional regulation in tuning Hmp
      levels to prevent exacerbation of the oxidative stress encountered in
      macrophages.

PMID- 17526835
TI  - Differential Salmonella survival against communities of intestinal amoebae.
AB  - Predation from intestinal amoebae may provide selective pressure for the
      maintenance of high genetic diversity at the Salmonella enterica rfb locus,
      whereby serovars better escape predators in particular environments depending on
      the O-antigens they express. Here, the hypothesis that amoebae from a particular
      intestinal environment collectively prefer one serovar over another is tested.
      Collections of Acanthamoeba, Tetramitus, Naegleria and Hartmannella were isolated
      from the intestinal tracts of several vertebrate hosts, including bullfrog
      tadpoles, goldfish, turtles and bearded dragons, and their feeding preferences
      were determined. Congeneric amoebae from the same environment had significantly
      similar feeding preferences. Strikingly, even unrelated amoebae - such as
      Naegleria and Tetramitus from goldfish - also had significantly similar feeding
      preferences. Yet amoebae isolated from different environments showed no
      similarity in prey choice. Thus, feeding preferences of amoebae appear to reflect
      their environment, not their taxonomic relationships. A mechanism mediating this
      phenotypic convergence is discussed.

PMID- 17526836
TI  - Characterization of the integrated filamentous phage Pf5 and its involvement in
      small-colony formation.
AB  - Bacteriophages play an important role in bacterial virulence and phenotypic
      variation. It has been shown that filamentous bacteriophage Pf4 of Pseudomonas
      aeruginosa strain PAO1 mediates the formation of small-colony variants (SCVs) in
      biofilms. This morphology type is associated with parameters of poor lung
      function in cystic fibrosis patients, and SCVs are often more resistant to
      antibiotics than wild-type cells. P. aeruginosa strain PA14 also contains a Pf1
      like filamentous prophage, which is designated Pf5, and is highly homologous to
      Pf4. Since P. aeruginosa PA14 produces SCVs very efficiently in biofilms grown in
      static cultures, the role of Pf5 in SCV formation under these conditions was
      investigated. The presence of the Pf5 replicative form in total DNA from SCVs and
      wild-type cells was detected, but it was not possible to detect the Pf5 major
      coat protein by immunoblot analysis in PA14 SCV cultures. This suggests that the
      Pf5 filamentous phage is not present at high densities in the PA14 SCVs.
      Consistent with these results, we were unable to detect coaB expression in SCV
      cultures and SCV colonies. The SCV variants formed under static conditions were
      not linked to Pf5 phage activity, since Pf5 insertion mutants with decreased or
      no production of the Pf5 RF produced SCVs as efficiently as the wild-type strain.
      Finally, analysis of 48 clinical P. aeruginosa isolates showed no association
      between the presence of Pf1-like filamentous phages and the ability to form SCVs
      under static conditions; this suggests that filamentous phages are generally not
      involved in the emergence of P. aeruginosa SCVs.

PMID- 17526837
TI  - The response regulator ComE in Streptococcus mutans functions both as a
      transcription activator of mutacin production and repressor of CSP biosynthesis.
AB  - In Streptococcus pneumoniae, competence and bacteriocin genes are controlled by
      two two-component systems, ComED and BlpRH, respectively. In Streptococcus
      mutans, both functions are controlled by the ComED system. Recent studies in S.
      mutans revealed a potential ComE binding site characterized by two 11 bp direct
      repeats shared by each of the bacteriocin genes responsive to the competence
      stimulating peptide (CSP). Interestingly, this sequence was not found in the
      upstream region of the CSP structural gene comC. Since comC is suggested to be
      part of a CSP-responsive and ComE-dependent autoregulatory loop, it was of
      interest to determine how it was possible that the ComED system could
      simultaneously regulate bacteriocin expression and natural competence. Using the
      intergenic region IGS1499, shared by the CSP-responsive bacteriocin nlmC and
      comC, it was demonstrated that both genes are likely to be regulated by a
      bifunctional ComE. In a comE null mutant, comC gene expression was increased
      similarly to a fully induced wild-type. In contrast, nlmC gene expression was
      nearly abolished. Deletion of ComD exerted a similar effect on both genes to that
      observed with the comE null mutation. Electrophoretic mobility shift assays
      (EMSAs) with purified ComE revealed specific shift patterns dependent on the
      presence of one or both direct repeats in the nlmC-comC promoter region. The two
      direct repeats were also required for the promoter activity of both nlmC and
      comC. These results suggest that gene regulation of comC in S. mutans is
      fundamentally different from that reported for S. pneumoniae, which implicates a
      unique regulatory mechanism that allows the coordination of bacteriocin
      production with competence development.

PMID- 17526838
TI  - Butane monooxygenase of 'Pseudomonas butanovora': purification and biochemical
      characterization of a terminal-alkane hydroxylating diiron monooxygenase.
AB  - Butane monooxygenase (sBMO) has been purified to homogeneity from the Gram
      negative beta-proteobacterium 'Pseudomonas butanovora' and confirmed to be a
      three-component diiron monooxygenase system. The reconstituted enzyme complex
      oxidized C(3)-C(6) linear and branched aliphatic alkanes, which are growth
      substrates for 'P. butanovora'. The sBMO complex was composed of an iron
      containing hydroxylase (BMOH), a flavo-iron sulfur-containing NADH-oxidoreductase
      (BMOR) and a small regulatory component protein (BMOB). The physical
      characteristics of sBMO were remarkably similar to the sMMO family of soluble
      multicomponent diiron monooxgenases. However, the catalytic properties of sBMO
      were quantitatively different in regard to inactivation in the presence of
      substrate and product distribution. BMOH was capable of ethene oxidation when
      supplied with H(2)O(2) and ethene (known as the peroxide shunt), but this
      activity was at least three orders of magnitude less than that observed for the
      hydroxylase of sMMO of Methylosinus trichosporium OB3b. BMOH and BMOR were
      efficient in the oxidation of ethene in the absence of BMOB with regard to rate
      of reaction and product yield. Regiospecificity of sBMO was strongly biased
      towards primary hydroxylation, with > or = 80 % of the hydroxylations occurring
      at the terminal carbon atom.

PMID- 17526839
TI  - gamma-Butyrolactone autoregulator-receptor system involved in lankacidin and
      lankamycin production and morphological differentiation in Streptomyces rochei.
AB  - An afsA homologue (srrX) and three gamma-butyrolactone receptor gene homologues
      (srrA, srrB and srrC) are coded on the giant linear plasmid pSLA2-L in
      Streptomyces rochei 7434AN4, a producer of two polyketide antibiotics, lankacidin
      and lankamycin. Construction of gene disruptants and their phenotypic study
      revealed that srrX and srrA make a gamma-butyrolactone receptor system in this
      strain. Addition of a gamma-butyrolactone fraction to an srrX-deficient mutant
      restored the production of lankacidin and lankamycin, indicating that the SrrX
      protein is not necessary for this event. In addition to a positive effect on
      antibiotic production, srrX showed a negative effect on morphological
      differentiation. The receptor gene srrA reversed both effects of srrX, while the
      second receptor gene homologue srrC had only a positive function in spore
      formation. Furthermore, disruption of the third homologue srrB greatly increased
      the production of lankacidin and lankamycin. Electron microscopic analysis showed
      that aerial mycelium formation stopped at a different stage in the srrA and srrC
      mutants. Overall, these results indicated that srrX, srrA, srrB and srrC
      constitute a complex regulatory system for antibiotic production and
      morphological differentiation in S. rochei.

PMID- 17526840
TI  - Three different DnaK proteins are functionally expressed in the cyanobacterium
      Synechocystis sp. PCC 6803.
AB  - Multiple dnaK genes appear to be common in cyanobacteria; the function of the
      encoded proteins is, however, still elusive. To characterize the dnaK gene family
      from the cyanobacterium Synechocystis sp. PCC 6803 in detail, genetic analyses
      were combined with analyses of the expression and localization patterns of the
      three encoded proteins. While significant expression of all three genes was
      found, the results obtained clearly indicate physiological differences of the
      three proteins in vivo, and DnaK2 seems to have a key function in Synechocystis.
      Expression of DnaK3 appears also to be as essential as expression of DnaK2,
      whereas the dnaK1 gene was deleted without resulting in any distorted phenotype.
      In line with a suggested privileged function, expression of DnaK2 altered most
      significantly after heat shock.

PMID- 17526841
TI  - The phrA gene of Rhodobacter sphaeroides encodes a photolyase and is regulated by
      singlet oxygen and peroxide in a sigma(E)-dependent manner.
AB  - The genome of the facultatively photosynthetic bacterium Rhodobacter sphaeroides
      encodes three proteins of the photolyase/cryptochrome family. This paper shows
      that phrA (RSP2143) encodes a functional photolyase, which is an enzyme that
      repairs UV radiation-induced DNA damage in a blue light dependent manner.
      Expression of phrA is upregulated in response to light, with no photoreceptor or
      the photosynthetic electron transport being involved. The results reveal that
      singlet oxygen and hydrogen peroxide dependent signals are transmitted by the
      sigma(E) factor and the anti-sigma(E) factor ChrR affecting phrA expression,
      while superoxide anions do not stimulate phrA expression. Thus, the sigma(E)
      regulon is involved not only in the response to singlet oxygen but also in the
      hydrogen peroxide response.

PMID- 17526842
TI  - Hypermutability in environmental Pseudomonas aeruginosa and in populations
      causing pulmonary infection in individuals with cystic fibrosis.
AB  - Pseudomonas aeruginosa is the pathogen most commonly associated with morbidity
      and mortality in cystic fibrosis (CF) patients. The host-pathogen interactions
      responsible for progressive CF lung diseases are complex. However, there is
      growing interest in the role of hypermutable P. aeruginosa (that is, those
      strains with an increased mutation frequency due to mutations in mismatch repair
      and error prevention genes), in terms of both bacterial adaptation and
      antimicrobial resistance. The prevalence of hypermutable P. aeruginosa in chronic
      CF infection has been established, and at 37 % is surprisingly high. To the
      authors' knowledge, there are no reports of prevalence during the early stages of
      infection, in environmental pseudomonas, which are believed to be the primary
      source of infection, and in epidemic strains, which have emerged as a major
      challenge. The aim of this study was to establish the prevalence of hypermutable
      P. aeruginosa in these pseudomonas populations. The hypothesis was that
      hypermutability would be rare in early and in environmental P. aeruginosa but in
      contrast would explain the relatively recent emergence of epidemic strains. It
      was found that 10/100 (10 %) of early isolates were strong or weak mutators,
      suggesting that the CF lung is not the only factor influencing the existence of
      mutators in this group of patients. Two weak mutators (6 %) were found in 32
      environmental isolates. Only two of 15 (13 %) epidemic P. aeruginosa strains were
      hypermutable, and although closer analysis revealed this issue to be complex, on
      the whole the data suggested that the atypical characteristics of these highly
      transmissible strains cannot solely be explained by this phenomenon. The higher
      than predicted prevalence of mutators in early infection, and in environmental
      isolates, reinforces the importance of early and aggressive treatment for P.
      aeruginosa infection in CF.

PMID- 17526843
TI  - Study of factors which negatively affect expression of the phenol degradation
      operon pheBA in Pseudomonas putida.
AB  - Transcription of the plasmid-borne phenol catabolic operon pheBA in Pseudomonas
      putida is activated by the LysR-family regulator CatR in the presence of the
      effector molecule cis,cis-muconate (CCM), which is an intermediate of the phenol
      degradation pathway. In addition to the positive control of the operon, several
      factors negatively affect transcription initiation from the pheBA promoter.
      First, the activation of the pheBA operon depends on the extracellular
      concentration of phenol. The pheBA promoter is rapidly activated in the presence
      of micromolar concentrations of phenol in minimal growth medium, but the
      initiation of transcription from this promoter is severely delayed after sudden
      exposure of bacteria to 2.5 mM phenol. Second, the transcriptional activation
      from this promoter is impeded when the growth medium of bacteria contains amino
      acids. The negative effects of amino acids can be suppressed either by
      overproducing CatR or by increasing, the intracellular amount of CCM. However,
      the intracellular amount of CCM is a major limiting factor for the
      transcriptional activation of the pheBA operon, as accumulation of CCM in a P.
      putida catB-defective strain, unable to metabolize CCM (but expressing CatR at a
      natural level), almost completely relieves the negative effects of amino acids.
      The intracellular amount of CCM is negatively affected by the catabolite
      repression control protein via downregulating at the post-transcriptional level
      the expression of the pheBA-encoded catechol 1,2-dioxygenase and the phenol
      monooxygenase, the enzymes needed for CCM production.

PMID- 17526844
TI  - The surface physicochemistry and adhesiveness of Shewanella are affected by their
      surface polysaccharides.
AB  - Shewanella strains have previously been studied with regard to their cell surface
      ultrastructure and LPS composition. They have now been further characterized with
      respect to their surface physicochemistry and ability to adhere to haematite. The
      surfaces of the Shewanella strains were found to be electronegative and
      hydrophilic, and these properties could be correlated with LPS composition or the
      presence of capsular polysaccharides. Strains expressing rough LPS with no
      capsule were more hydrophobic and electronegative than those possessing smooth
      LPS or capsules. By combining different approaches, such as contact-angle
      measurement, hydrophilic/hydrophobic chromatography, microelectrophoresis,
      adhesion assays and calculation of interaction energies, it was shown that
      electrostatic interactions predominate over hydrophobic interactions at the cell
      iron oxide interface. Bacterial adhesion to haematite was significantly reduced
      in strains expressing smooth LPS or a capsule. These findings remained true for
      Shewanella strains grown under either aerobic or anaerobic conditions, although
      the surfaces of anaerobic cells appeared to be less electronegative and more
      hydrophilic than those of aerobic cells.

PMID- 17526845
TI  - Plasmids derived from Gifsy-1/Gifsy-2, lambdoid prophages contributing to the
      virulence of Salmonella enterica serovar Typhimurium: implications for the
      evolution of replication initiation proteins of lambdoid phages and
      enterobacteria.
AB  - Gifsy-1 and Gifsy-2 are lambdoid prophages which contribute to the virulence of
      Salmonella enterica serovar Typhimurium. The nucleotide sequence of the
      replication region of both prophages is identical, and similar in organization to
      the replication region of bacteriophage lambda. To investigate the replication of
      the Gifsy phages and the relationship between Gifsy and host chromosome
      replication, a plasmid which contained all the genes and regulatory sequences
      required for autonomous replication in bacterial cells was constructed. This
      plasmid, pGifsy, was stably maintained in Escherichia coli cells. The helicase
      loader of the Gifsy phages is very similar to the DnaC protein of the host, a
      feature characteristic of a large group of prophages common in the sequenced
      genomes of pathogenic enterobacteria. This DnaC-like protein showed no similarity
      to the helicase loader of bacteriophage lambda and closely related phages.
      Interestingly, unlike plasmids derived from bacteriophage lambda (lambda
      plasmids), pGifsy did not require a gene encoding the putative helicase loader
      for replication, although deletion of this gene resulted in a decrease in plasmid
      copy number. Under these conditions, it was shown that the plasmid utilized the
      helicase loader coded by the host. On the other hand, the viral protein could not
      substitute for DnaC in bacterial chromosome replication. The results of the
      current study support the hypothesis that the enterobacterial helicase loader is
      of viral origin. This hypothesis explains why the gene for DnaC, the protein
      central to both replication initiation and replication restart in E. coli, is
      present in the genomes of Escherichia, Shigella, Salmonella and Buchnera, but not
      in the genomes of related enterobacteria.

PMID- 17526846
TI  - Characterization of a catalase gene from Aeromonas veronii, the digestive-tract
      symbiont of the medicinal leech.
AB  - The catalase gene katA of the medicinal leech symbiont Aeromonas veronii bv.
      sobria was cloned, sequenced, and functionally characterized. Southern
      hybridization, using an A. veronii katA-specific hybridization probe, suggested
      the presence of a single gene copy in many Aeromonas species. A. veronii katA
      consisted of 1446 nt encoding a protein with a high degree of similarity to the
      small-subunit group III bacterial catalases. A catalase-null mutant (JG186) was
      constructed through gene-replacement mutagenesis. In the parent strain (HM21R),
      catalase activity was only detected in extracts of cells grown to early
      exponential phase following H(2)O(2) induction, in which the ability to induce
      activity was inversely related to optical density. In contrast, induced JG186
      cells were very sensitive to oxidative stress, with survival being affected even
      at low H(2)O(2) concentrations. In contrast to the findings of previous reports
      of other symbiotic systems, the catalase mutant was not defective in its ability
      to competitively colonize or persist within its host, in both co-inoculation and
      sole-colonization assays. This body of evidence suggests either that oxidative
      stress, in the form of H(2)O(2) exposure, is not encountered by the microbial
      partner under the examined symbiotic conditions or that compensatory mechanisms
      exist. The data suggest that although many colonization factors reoccur, each
      symbiotic system has also evolved specific mechanisms that affect symbiont-host
      dynamics.

PMID- 17526847
TI  - Characterization of two distinct phospholipase C enzymes from Burkholderia
      pseudomallei.
AB  - Burkholderia pseudomallei is a serious bacterial pathogen that can cause a lethal
      infection in humans known as melioidosis. In this study two of its phospholipase
      C (PLC) enzymes (Plc-1 and Plc-2) were characterized. Starting with a virulent
      strain, two single mutants were constructed, each with one plc gene inactivated,
      and one double mutant with both plc genes inactivated. The single plc mutants
      exhibited decreased extracellular PLC activity in comparison to the wild-type
      strain, thereby demonstrating that the two genes encoded functional extracellular
      PLCs. Growth comparisons between the wild-type and PLC mutants in egg-yolk
      supplemented medium indicated that both PLCs contributed to egg-yolk phospholipid
      utilization. Both PLCs hydrolysed phosphatidylcholine and sphingomyelin but
      neither was haemolytic for human erythrocytes. Experimental infections of
      eukaryotic cells demonstrated that Plc-1 itself had no effect on plaque-forming
      efficiency but it had an additive effect on increasing the efficiency of Plc-2 to
      form plaques. Only Plc-2 had a significant role in host cell cytotoxicity. In
      contrast, neither Plc-1 nor Plc-2 appeared to play any role in multinucleated
      giant cell (MNGC) formation or induction of apoptotic death in the cells studied.
      These data suggested that PLCs contribute, at least in part, to B. pseudomallei
      virulence and support the view that Plc-1 and Plc-2 are not redundant virulence
      factors.

PMID- 17526848
TI  - Involvement of minor components associated with the FimA fimbriae of
      Porphyromonas gingivalis in adhesive functions.
AB  - The FimA fimbriae of Porphyromonas gingivalis, the causative agent of
      periodontitis, have been implicated in various aspects of pathogenicity, such as
      colonization, adhesion and aggregation. In this study, the four open reading
      frames (ORF1, ORF2, ORF3 and ORF4) downstream of the fimbrilin gene (fimA) in
      strain ATCC 33277 were examined. ORF2, ORF3 and ORF4 were demonstrated to encode
      minor components of the fimbriae and were therefore renamed fimC, fimD and fimE,
      respectively. Immunoblotting analyses revealed that inactivation of either fimC
      or fimD by an ermF-ermAM insertion, but not inactivation of ORF1, was accompanied
      by concomitant loss of the products from the downstream genes, raising the
      possibility that fimC, fimD and fimE constitute a transcription unit. The fimE
      mutant produced FimC and FimD, but fimbriae purified from it contained neither
      protein, suggesting that FimE is required for the assembly of FimC and FimD onto
      the fimbrilin (FimA) fibre. The fimC, fimD and fimE mutants lost autoaggregation
      abilities. Fimbriae purified from these three mutants showed attenuated binding
      activities to glyceraldehyde-3-phosphate dehydrogenase of Streptococcus oralis
      and to two extracellular matrix proteins, fibronectin and type I collagen. These
      results suggest that FimE, as well as FimC and FimD, play critical roles in the
      adhesive activities of the mature FimA fimbriae in P. gingivalis.

PMID- 17526849
TI  - Phenotypic and genotypic characterization of a new fish-virulent Vibrio
      vulnificus serovar that lacks potential to infect humans.
AB  - Vibrio vulnificus is a bacterial species that is virulent for humans and fish.
      Human isolates are classified into biotypes 1 and 3 (BT1 and BT3) and fish
      isolates into biotype 2 (BT2). However, a few human infections caused by BT2
      isolates have been reported worldwide (zoonosis). These BT2 human isolates belong
      to serovar E (SerE), which is also present in diseased fish. The aim of the
      present work was to characterize a new BT2 serovar [serovar A (SerA)], which
      emerged in the European fish-farming industry in 2000, by means of phenotypic,
      serological and genetic [plasmid profiling, ribotyping and random amplified
      polymorphic DNA (RAPD)] methodologies. The results confirmed that SerA
      constitutes a homogeneous O-serogroup within the species that shares plasmidic
      information with SerE. Like SerE, this new serogroup was resistant to fresh fish
      serum, as well as being highly virulent for fish. In contrast, it was sensitive
      to human serum and avirulent for mice, even after pretreatment with iron. The two
      serovars presented different biochemical profiles as well as specific patterns by
      ribotyping and RAPD analysis. In conclusion, SerA seems to constitute a different
      clonal group that has recently emerged within the species V. vulnificus, with
      pathogenic potential for fish but not for humans.

PMID- 17526850
TI  - Effect of host fatty acid-binding protein and fatty acid uptake on growth of
      Chlamydia trachomatis L2.
AB  - Chlamydia trachomatis is an obligate intracellular bacterium and acquires both
      building blocks and energy from host cells for growth. The fatty acid-binding
      protein (FABP) plays an important role in uptake of long-chain fatty acids (LCFA)
      and energy metabolism by eukaryotic cells. The roles of FABP and LCFA in
      chlamydial infection were evaluated. Infection of liver cells with chlamydial
      organisms promoted fatty acid uptake by the infected cells, suggesting that LCFA
      may benefit chlamydial growth. Introduction of FABP into the liver cells not only
      enhanced fatty acid uptake, but also increased chlamydial intravacuolar
      replication and maturation. The FABP-enhanced chlamydial intracellular growth was
      dependent on the host cell uptake of fatty acids. These results have demonstrated
      that C. trachomatis can productively infect liver cells and utilize FABP
      transported LCFA for its own biosynthesis.

PMID- 17526851
TI  - Role in virulence and protective efficacy in pigs of Salmonella enterica serovar
      Typhimurium secreted components identified by signature-tagged mutagenesis.
AB  - Salmonella enterica serovar Typhimurium (S. Typhimurium) is a zoonotic enteric
      pathogen of worldwide importance and pigs are a significant reservoir of human
      infection. Signature-tagged transposon mutagenesis (STM) was used to identify
      genes required by S. Typhimurium to colonize porcine intestines. A library of
      1045 signature-tagged mutants of S. Typhimurium ST4/74 Nal(R) was screened
      following oral inoculation of pigs in duplicate. A total of 119 attenuating
      mutations were identified in 95 different genes, many of which encode known or
      putative secreted or surface-anchored molecules. A large number of attenuating
      mutations were located within Salmonella pathogenicity islands (SPI)-1 and -2,
      confirming important roles for type III secretion systems (T3SS)-1 and -2 in
      intestinal colonization of pigs. Roles for genes encoded in other pathogenicity
      islands and islets, including the SPI-6-encoded Saf atypical fimbriae, were also
      identified. Given the role of secreted factors and the protection conferred
      against other pathogens by vaccination with extracellular and type III secreted
      proteins, the efficacy of a secreted protein vaccine from wild-type S.
      Typhimurium following intramuscular vaccination of pigs was evaluated. Serum IgG
      responses against type III secreted proteins were induced following vaccination
      and a significant reduction in faecal excretion of S. Typhimurium was observed in
      the acute phase of infection compared to mock-vaccinated animals. Vaccination
      with secreted proteins from an isogenic S. Typhimurium prgH mutant produced
      comparable levels of protection to vaccination with the preparation from the
      parent strain, indicating that protection was not reliant on T3SS-1 secreted
      proteins. The data provide valuable information for the control of Salmonella in
      pigs.

PMID- 17526852
TI  - EscC is a chaperone for the Edwardsiella tarda type III secretion system putative
      translocon components EseB and EseD.
AB  - Edwardsiella tarda is a Gram-negative enteric pathogen that causes disease in
      both humans and animals. Recently, a type III secretion system (T3SS) has been
      found to contribute to Ed. tarda pathogenesis. EseB, EseC and EseD were shown to
      be secreted by the T3SS and to be the major components of the extracellular
      proteins (ECPs). Based on sequence similarity, they have been proposed to
      function as the 'translocon' of the T3SS needle structure. In this study, it was
      shown that EseB, EseC and EseD formed a protein complex after secretion, which is
      consistent with their possible roles as translocon components. The secretion of
      EseB and EseD was dependent on EscC (previously named Orf2). EscC has the
      characteristics of a chaperone; it is a small protein (13 kDa), located next to
      the translocators in the T3SS gene cluster, and has a coiled-coil structure at
      the N-terminal region as predicted by coils. An in-frame deletion of escC
      abolished the secretion of EseB and EseD, and complementation of DeltaescC
      restored the export of EseB and EseD into the culture supernatant. Further
      studies showed that EscC is not a secreted protein and is located on the membrane
      and in the cytoplasm. Mutation of escC did not affect the transcription of eseB
      but reduced the amount of EseB as measured by using an EseB-LacZ fusion protein
      in Ed. tarda. Co-purification studies demonstrated that EscC formed complexes
      with EseB and EseD. The results suggest that EscC functions as a T3SS chaperone
      for the putative translocon components EseB and EseD in Ed. tarda.

PMID- 17526853
TI  - Glucose uptake and growth of glucose-limited chemostat cultures of Aspergillus
      niger and a disruptant lacking MstA, a high-affinity glucose transporter.
AB  - This is a study of high-affinity glucose uptake in Aspergillus niger and the
      effect of disruption of a high-affinity monosaccharide-transporter gene, mstA.
      The substrate saturation constant (K(s)) of a reference strain was about 15
      microM in glucose-limited chemostat culture. Disruption of mstA resulted in a two
      to fivefold reduction in affinity for glucose and led to expression of a low
      affinity glucose transport gene, mstC, at high dilution rate. The effect of mstA
      disruption was more subtle at low and intermediate dilution rates, pointing to
      some degree of functional redundancy in the high-affinity uptake system of A.
      niger. The mstA disruptant and a reference strain were cultivated in glucose
      limited chemostat cultures at low, intermediate and high dilution rate (D=0.07 h(
      1), 0.14 h(-1) and 0.20 h(-1)). Mycelium harvested from steady-state cultures was
      subjected to glucose uptake assays, and analysed for expression of mstA and two
      other transporter genes, mstC and mstF. The capacity for glucose uptake (v(max))
      of both strains was significantly reduced at low dilution rate. The glucose
      uptake assays revealed complex uptake kinetics. This impeded accurate
      determination of maximum specific uptake rates (v(max)) and apparent affinity
      constants ( ) at intermediate and high dilution rate. Two high-affinity glucose
      transporter genes, mstA and mstF, were expressed at all three dilution rates in
      chemostat cultures, in contrast to batch culture, where only mstC was expressed.
      Expression patterns of the three transporter genes suggested differential
      regulation and functionality of their products.

PMID- 17526854
TI  - Changes in the redox state and composition of the quinone pool of Escherichia
      coli during aerobic batch-culture growth.
AB  - Ubiquinones (UQs) and menaquinones (MKs) perform distinct functions in
      Escherichia coli. Whereas, in general, UQs are primarily involved in aerobic
      respiration, the MKs serve as electron carriers in anaerobic respiration. Both
      UQs and MKs can accept electrons from various dehydrogenases, and may donate
      electrons to different oxidases. Hence, they play a role in maintaining metabolic
      flexibility in E. coli whenever this organism has to adapt to conditions with
      changing redox characteristics, such as oxygen availability. Here, the authors
      report on the changes in both the size and the redox state of the quinone pool
      when the environment changes from being well aerated to one with low oxygen
      availability. It is shown that such transitions are accompanied by a rapid
      increase in the demethylmenaquinone pool, and a slow increase in the MK pool.
      Moreover, in exponentially growing cultures in a well-shaken Erlenmeyer flask, it
      is observed that the assumption of a pseudo-steady state does not hold with
      respect to the redox state of the quinone pool.

PMID- 17526855
TI  - Methyl-beta-cyclodextrin alters growth, activity and cell envelope features of
      sterol-transforming mycobacteria.
AB  - Modified beta-cyclodextrins have been shown previously to enhance sterol
      conversion to 4-androstene-3,17-dione (AD) and 1,4-androstadiene-3,17-dione (ADD)
      by growing Mycobacterium spp. The enhancement effect was mainly attributed to
      steroid solubilization by the formation of inclusion complexes with modified
      cyclodextrins. In this work, the influence of randomly methylated beta
      cyclodextrin (MCD) on the growth, AD- and ADD-producing activity, cell wall (CW)
      composition and ultrastructure of sterol-transforming Mycobacterium sp. VKM Ac
      1816D was studied. The specific growth rate of the strain on glycerol increased
      in the presence of MCD (20-100 mM). Washed cells grown in the presence of MCD (20
      40 mM) expressed 1.6-fold higher ADD-producing activity than did the cells grown
      without MCD, and their adhesiveness differed. Electron microscopy showed MCD
      mediated CW exfoliation and accumulation of membrane-like structures outside the
      cells, while preserving cells intact. The analysis of CW composition revealed
      both a decrease in the proportion of extractable lipids and a considerable shift
      in fatty acid profile resulting from MCD action. The MCD-mediated enhancement of
      mycolic and fatty acids content was observed outside the cells. The total
      secreted protein level rose 2.4-fold, and the extracellular 3-hydroxysteroid
      oxidase activity 3.2-fold. The composition of the CW polysaccharide was not
      altered, while the overall proportion of the carbohydrates in the CW of the MCD
      exposed mycobacteria increased. The results showed that the multiple mechanisms
      of MCD-mediated intensification of sterol to AD(D) conversion by mycobacteria
      include not only solubilization of steroids, but also the increase of CW
      permeability for both steroids and soluble nutrients, disorganization of the
      lipid bilayer and the release of steroid-transforming enzymes weakly associated
      with the CW.

PMID- 17526857
TI  - Pharmacokinetic evaluation of emtricitabine in combination with other nucleoside
      antivirals in healthy volunteers.
AB  - Emtricitabine is a potent nucleoside reverse transcriptase inhibitor approved as
      a once-daily drug in combination with other antiretroviral agents for the
      treatment of HIV infection. Several phase I studies were conducted in healthy
      volunteers over the course of clinical development to evaluate whether
      pharmacokinetic drug-drug interactions exist between emtricitabine and other
      nucleoside antivirals that are extensively eliminated by renal excretion.
      Potential interactions with stavudine and famciclovir were evaluated in single
      dose studies, whereas interactions with zidovudine and its major metabolite,
      zidovudine glucuronide, were evaluated in a multiple-dose study. Plasma
      pharmacokinetic profiles and, in some studies, urinary excretion data were
      evaluated when each drug was administered alone and in combination with
      emtricitabine. Safety and plasma pharmacokinetic profiles of each drug
      administered alone or with emtricitabine were consistent with historical data.
      Statistical analyses indicated that there were no significant interactions
      between emtricitabine and these 3 nucleoside antivirals.

PMID- 17526858
TI  - Pharmacokinetics and pharmacodynamics of mycophenolic acid after enteric-coated
      mycophenolate versus mycophenolate mofetil in patients with progressive IgA
      nephritis.
AB  - Mycophenolic acid can be administered orally using mycophenolate mofetil or
      enteric-coated mycophenolate. In renal transplant patients on immunosuppressant
      combination therapy, the overall mycophenolic acid exposure after oral dosing
      with mycophenolate mofetil and enteric-coated mycophenolate is similar. This
      study compared pharmacokinetics and pharmacodynamics of mycophenolic acid after
      equivalent doses of enteric-coated mycophenolate (360 mg twice daily) or
      mycophenolate mofetil (500 mg twice daily) in 7 patients with progressive IgA
      nephritis (glomerular filtration rate 20-35 mL/min) using a randomized crossover
      design. The pharmacokinetics of mycophenolic acid concentrations and
      pharmacodynamics (using inosine 5'-monophosphate dehydrogenase activity as a bio
      marker) were sequentially monitored for 12 hours. After enteric-coated
      mycophenolate treatment, the mycophenolic acid peak concentration (Cmax = 12.8 vs
      6.0 microg/mL, P < .05) and the overall exposure were significantly higher (AUC =
      60.9 vs 40.7 microg.h/mL, P < .05), and the apparent clearance was significantly
      lower (CL/F = 7.9 vs 10.7 L/h, P < .05) as compared to that after mycophenolate
      mofetil. Paradoxically, inosine 5'-monophosphate dehydrogenase activity was not
      significantly different. In conclusion, the steady-state mycophenolic acid
      exposure was higher during treatment with enteric-coated mycophenolate as
      compared to mycophenolate mofetil, which might be explained by more extensive
      enterohepatic recycling of mycophenolic acid after administration of enteric
      coated mycophenolate, whereas inosine 5'-monophosphate dehydrogenase suppression
      was not different.

PMID- 17526859
TI  - Lymphotoxin a-dependent and -independent signals regulate stromal organizer cell
      homeostasis during lymph node organogenesis.
AB  - Lymph nodes provide specialized stromal microenvironments that support the
      recruitment and organization of T cells and B cells, enabling them to effectively
      participate in immune responses. While CD4(+)3(-) lymphoid tissue inducer cells
      (LTic's) are known to play a key role in influencing lymph node (LN) development,
      the mechanisms that regulate the development of stromal organizer cells are
      unclear. Here, we define an ontogenetic program of lymph node stromal cell
      maturation in relation to the requirement for LTic's. We also describe a lymph
      node reaggregation assay to study cell-cell interactions and lymphocyte
      recruitment to these organs that reproduces the in vivo events during lymph node
      development. In addition, analysis of the lymph node anlagen in normal and
      lymphotoxin a (LTa)-deficient embryos shows that LTa-mediated signaling is
      required to sustain proliferation and survival of stromal cells in vivo. Our data
      identify LTa-independent and LTa-dependent stages of lymph node development, and
      provide direct evidence for the role of LTic's during LN organogenesis.

PMID- 17526860
TI  - Hematopoietic stem-cell behavior in nonhuman primates.
AB  - Little is known about the behavior of hematopoietic stem cells (HSCs) in primates
      because direct observations and competitive-repopulation assays are not feasible.
      Therefore, we used 2 different and independent experimental strategies, the
      tracking of transgene expression after retroviral-mediated gene transfer (N = 11
      baboons; N = 7 rhesus macaques) and quantitation of the average telomere length
      of granulocytes (N = 132 baboons; N = 14 macaques), together with stochastic
      methods, to study HSC kinetics in vivo. The average replication rate for baboon
      HSCs is once per 36 weeks according to gene-marking analyses and once per 23
      weeks according to telomere-shortening analyses. Comparable results were derived
      from the macaque data. These rates are substantially slower than the average
      replication rates previously reported for HSCs in mice (once per 2.5 weeks) and
      cats (once per 8.3 weeks). Because baboons and macaques live for 25 to 45 years,
      much longer than mice ( approximately 2 years) and cats (12-18 years), we can
      compute that HSCs undergo a relatively constant number ( approximately 80-200) of
      lifetime replications. Thus, our data suggest that the self-renewal capacity of
      mammalian stem cells in vivo is defined and evolutionarily conserved.

PMID- 17526861
TI  - Cytoplasmic remodeling of erythrocyte raft lipids during infection by the human
      malaria parasite Plasmodium falciparum.
AB  - Studies of detergent-resistant membrane (DRM) rafts in mature erythrocytes have
      facilitated identification of proteins that regulate formation of endovacuolar
      structures such as the parasitophorous vacuolar membrane (PVM) induced by the
      malaria parasite Plasmodium falciparum. However, analyses of raft lipids have
      remained elusive because detergents interfere with lipid detection. Here, we use
      primaquine to perturb the erythrocyte membrane and induce detergent-free buoyant
      vesicles, which are enriched in cholesterol and major raft proteins flotillin and
      stomatin and contain low levels of cytoskeleton, all characteristics of raft
      microdomains. Lipid mass spectrometry revealed that phosphatidylethanolamine and
      phosphatidylglycerol are depleted in endovesicles while phosphoinositides are
      highly enriched, suggesting raft-based endovesiculation can be achieved by simple
      (non-receptor-mediated) mechanical perturbation of the erythrocyte plasma
      membrane and results in sorting of inner leaflet phospholipids. Live-cell imaging
      of lipid-specific protein probes showed that phosphatidylinositol (4,5)
      bisphosphate (PIP(2)) is highly concentrated in primaquine-induced vesicles,
      confirming that it is an erythrocyte raft lipid. However, the malarial PVM lacks
      PIP(2), although another raft lipid, phosphatidylserine, is readily detected.
      Thus, different remodeling/sorting of cytoplasmic raft phospholipids may occur in
      distinct endovacuoles. Importantly, erythrocyte raft lipids recruited to the
      invasion junction by mechanical stimulation may be remodeled by the malaria
      parasite to establish blood-stage infection.

PMID- 17526862
TI  - Treatment of severe aplastic anemia with antithymocyte globulin and cyclosporin A
      with or without G-CSF in adults: a multicenter randomized study in Japan.
AB  - We report the results of a randomized study to elucidate whether addition of
      granulocyte colony-stimulating factor (G-CSF) to immunosuppressive therapy is
      valuable for the treatment of severe aplastic anemia (SAA) in adults. A total of
      101 previously untreated patients (median age, 54 years; range, 19 to 75 years)
      were randomized to receive antithymocyte globulin (ATG) and cyclosporin A (CyA)
      (G-CSF- group) or ATG, CyA, and G-CSF (G-CSF+ group). In the G-CSF+ group, the
      hematologic response rate at 6 months was higher (77% vs 57%; P = .03) than in
      the G-CSF- group. No differences were observed between the groups in terms of the
      incidence of infections and febrile episodes. There were no differences between
      the G-CSF- group and the G-CSF+ group in terms of survival (88% vs 94% at 4
      years), and the development of myelodysplastic syndrome (MDS)/acute leukemia (AL)
      (1 patient vs 2 patients). However, the relapse rate was lower in the G-CSF+
      group compared with the G-CSF- group (42% vs 15% at 4 years; P = .01). Further
      follow-up is required to elucidate the role of G-CSF in immunosuppressive therapy
      for adult SAA.

PMID- 17526863
TI  - Re: "Variable selection for propensity score models".

PMID- 17526864
TI  - Association between glycosylated hemoglobin level and cardiovascular and all
      cause mortality in type 1 diabetes.
AB  - Hyperglycemia is implicated in the development and progression of microvascular
      complications in type 1 diabetes. In contrast, the association between
      hyperglycemia and macrovascular complications or mortality in type 1 diabetes is
      not clear. The authors studied a population-based cohort of 879 individuals with
      type 1 diabetes from Wisconsin, free of cardiovascular disease and end-stage
      renal disease at the baseline examination (1980-1982). The main outcome of
      interest was all-cause (n=201) and cardiovascular (n=132) mortality as of
      December 31, 2001. Elevated glycosylated hemoglobin levels were associated with
      all-cause and cardiovascular mortality, independent of duration of diabetes,
      smoking, hypertension, and proteinuria. The multivariable relative risks
      comparing the highest quartile of glycosylated hemoglobin (>or=12.1%) with the
      lowest quartile (<or=9.4%) were 2.42 (95% confidence interval: 1.54, 3.82; p
      trend=0.0006) for all-cause mortality and 3.28 (95% confidence interval: 1.77,
      6.08; p-trend<0.0001) for cardiovascular mortality. This association was present
      among both sexes and persisted in subgroup analyses by categories of diabetes
      duration, smoking, body mass index, proteinuria, and retinopathy. These data
      suggest that hyperglycemia is associated with all-cause and cardiovascular
      mortality among individuals with type 1 diabetes.

PMID- 17526865
TI  - Passive smoking, metabolic gene polymorphisms, and infant birth weight in a
      prospective cohort study of Chinese women.
AB  - The authors investigated whether polymorphisms in two maternal metabolic genes,
      cytochrome P-450 1A1 (CYP1A1) MspI and epoxide hydrolase 1 (EPHX1) Tyr113His,
      affect the association of maternal passive smoking with infant birth weight. The
      study was conducted in a cohort of 1,388 newly married mothers of liveborn
      singletons who worked in textile mills in Anqing, China, from 1996 to 2000.
      Multiple linear regression models were used to estimate the associations of
      passive smoking and genetic susceptibility with birth weight, with adjustment for
      important potential confounders. In the passive smoking group, there was a
      remarkable decrease in birth weight with the C/C6235 genotype (156.3 g, 95%
      confidence interval (CI): -283.6, -29.0) for CYP1A1 MspI and with Tyr/His113
      (93.8 g, 95% CI: -188.6, -1.1) as compared with His/His113 (244.6 g, 95% CI: 
      491.0, -1.9) for EPHX1. When results were stratified by maternal genotype,
      passive smoking conferred a significantly negative effect in the EPHX1 Tyr/His113
      group (103.5 g, 95% CI: -205.8, -9.2) and in the His/His113 group (687.3 g, 95%
      CI: -748.3, -178.3). The data further showed that there was a significant
      interaction between maternal passive smoking and maternal EPHX1 genotype for
      birth weight. The authors conclude that the CYP1A1 MspI and EPHX1 genotypes
      modified the association between maternal passive smoking and infant birth weight
      in this study, which is suggestive of possible gene-environment interaction.

PMID- 17526866
TI  - Multiparameter calibration of a natural history model of cervical cancer.
AB  - The objective of this study was to develop a comprehensive natural history model
      of human papillomavirus (HPV) and cervical cancer using a two-step approach to
      model calibration. In the first step, the authors utilized primary epidemiologic
      data from a longitudinal study of women in Brazil and identified a plausible
      range for each input parameter that produced model output within the 95%
      confidence intervals of the data. In the second step, they performed a
      simultaneous search over all input parameters to identify parameter sets that
      produced output consistent with data from multiple sources. A goodness-of-fit
      score was computed for 555,000 unique parameter sets using a likelihood-based
      approach, and a sample of good-fitting parameter sets was used in the model to
      illustrate the advantage of the calibration approach by projecting a range of
      benefits associated with cervical cancer prevention policies. The calibrated
      model had reasonable fit to the data in terms of duration and prevalence of HPV
      infection for high-risk types, prevalence of precancerous lesions, and incidence
      of cancer. The authors found that leveraging primary data from longitudinal
      studies provides unique opportunities for model parameterization of the
      unobservable nature of HPV infection and its role in the development of cervical
      cancer.

PMID- 17526867
TI  - Effects of cochlear implants on children's reading and academic achievement.
AB  - This article presents a critical analysis of empirical studies assessing literacy
      and other domains of academic achievement among children with cochlear implants.
      A variety of recent studies have demonstrated benefits to hearing, language, and
      speech from implants, leading to assumptions that early implantation and longer
      periods of implant should be associated with higher reading and academic
      achievement. This review, however, reveals that although there are clear benefits
      of cochlear implantation to achievement in young deaf children, empirical results
      have been somewhat variable. Examination of the literature with regard to reading
      achievement suggests that the lack of consistent findings might be the result of
      frequent failures to control potentially confounding variables such as age of
      implantation, language skills prior to implantation, reading ability prior to
      implantation, and consistency of implant use. Studies of academic achievement
      beyond reading are relatively rare, and the extent to which performance in such
      domains is mediated by reading abilities or directly influenced by hearing,
      language, and speech remains unclear. Considerations of methodological
      shortcomings in existing research as well as theoretical and practical questions
      yet to be addressed provide direction for future research.

PMID- 17526868
TI  - GAPN postacute care coordination improves hip fracture outcomes.
AB  - We tested the effectiveness of a nursing intervention model to improve health,
      function, and return-home outcomes in elders with hip fracture via a 2-year
      randomized clinical trial. Thirty three elders (age > 65 years) were tracked from
      hospital discharge to 12 months postfracture. The treatment group had a
      gerontologic advanced practice nurse as postacute care coordinator for 6 months
      who intervened with each elder regardless of the postacute care setting, making
      biweekly visits and/or phone calls. The coordinator assessed health and function,
      and informed elders, families, long-term care staff, and physicians of the
      patient's progress. The control group had care based on postacute facility
      protocols. Nonnormal distribution of data led to nonparametric analysis using
      Freidman's test with post hoc comparisons (Mann-Whitney U tests, Bonferroni
      adjustment). The treatment group had better function at 12 months on several
      activities and instrumental activities of daily living, and no differences in
      health, depression, or living situation.

PMID- 17526869
TI  - Chinese immigrants' management of their cardiovascular disease risk.
AB  - The authors have undertaken a series of grounded theory studies to describe and
      explain how ethnocultural affiliation and gender influence the process that
      cardiac patients undergo when faced with making behavior changes associated with
      reducing their cardiovascular disease (CVD) risk. Data were collected through
      audiorecorded semistructured interviews (using an interpreter as necessary), and
      the authors analyzed the data using constant comparative methods. The core
      variable that emerged through the series of studies was "meeting the challenge."
      Here, the authors describe the findings from a sample of Chinese immigrants (10
      men, 5 women) to Canada. The process of managing CVD risk for the Chinese
      immigrants was characterized by their extraordinary diligence in seeking multiple
      sources of information to enable them to manage their health.

PMID- 17526870
TI  - Endogenous endostatin inhibits choroidal neovascularization.
AB  - Endostatin, a fragment of the basement membrane component collagen XVIII,
      exhibits antiangiogenic properties in vitro and in vivo when high doses are
      administered. It is not known whether endogenous endostatin at physiological
      levels has a protective role as an inhibitor of pathological angiogenesis, such
      as choroidal neovascularization (CNV) in age-related macular degeneration. Using
      a laser injury model, we induced CNV in mice lacking collagen XVIII/endostatin
      and in control mice. CNV lesions in mutant mice were approximately 3-fold larger
      than in control mice and showed increased vascular leakage. These differences
      were independent of age-related changes at the choroid-retina interface.
      Ultrastructural analysis of the choroidal vasculature in mutant mice excluded
      morphological vascular abnormalities as a cause for the larger CNV lesions. When
      recombinant endostatin was administered to collagen XVIII/endostatin-deficient
      mice, CNV lesions were similar to those seen in control mice. In control mice
      treated with recombinant endostatin, CNV lesions were almost undetectable. These
      findings demonstrate that endogenous endostatin is an inhibitor of induced
      angiogenesis and that administration of endostatin potently inhibits CNV growth
      and vascular leakage. Endostatin may have a regulatory role in the pathogenesis
      of CNV and could be used therapeutically to inhibit growth and leakage of CNV
      lesions.

PMID- 17526871
TI  - Impact of ectomycorrhizal colonization of hybrid poplar on the remediation of
      diesel-contaminated soil.
AB  - Infection by ectomycorrhizal (ECM) fungi may benefit hybrid poplar growing in
      contaminated soils by providing greater access to water and nutrients and
      possibly protecting the trees from direct contact with toxic contaminants. The
      objective of this research was to determine the effect of colonization of the ECM
      fungus Pisolithus tinctorius (Pers.) Coker & Couch on hybrid poplar fine root
      production, biomass and N and P uptake when grown in diesel-contaminated soil
      (5000 mg diesel fuel kg soil(-1)). Commercially available Mycogrow Tree Tabs were
      the source of inoculum. A minirhizotron camera was used to provide the data
      necessary for estimating fine root production. Colonization of hybrid poplar
      roots (P. deltoides x [P. laurifolia x P. nigra] cv. Walker) by P. tinctorius
      increased total fine root production in diesel-contaminated soil to 56.58 g m(-2)
      compared to 22.59 g m(-2) in the uncolonized, diesel-contaminated treatment.
      Hybrid poplar leaf N and P concentrations were significantly greater in the
      diesel-contaminated/ECM-colonized treatment compared to the diesel
      contaminated/uncolonized treatment after 12 wk, while significantly less diesel
      fuel was recovered from the soil of the uncolonized treatment compared to the
      colonized treatment. Both planted treatments removed more contaminants from the
      soil than an unplanted control. Significantly greater concentrations of total
      petroleum hydrocarbons (TPH) were found sequestered in hybrid poplar root/fungal
      sheath complexes from the colonized treatment compared to the roots of the
      uncolonized treatment. The results of this study indicate that over a 12-wk
      growth period, ECM colonization of hybrid poplar in diesel-contaminated soils
      increased fine root production and whole-plant biomass, but inhibited removal of
      TPH from the soil.

PMID- 17526872
TI  - Geostatistical analysis and risk assessment on soil total nitrogen and total soil
      phosphorus in the Dongting Lake plain area, China.
AB  - Nonpoint-source pollution and water body eutrophication have become increasing
      concerns for scientists and policymakers. Nitrogen and phosphorus affect
      environmental pollution, especially lake eutrophication. To assess the
      environmental risk of soil total nitrogen (TN) and total phosphorus (TP)
      pollution, a typical ecological unit of Dongting Lake plain was selected as the
      experimental site. To verify the stationary of the data, a moving windows
      technique was adopted. Our results showed that Box-Cox transformation achieved
      normality in the data set and dampened the effect of outliers. The best
      theoretical model for semivariogram of TN and TP was a spherical model. The
      ordinary kriging estimates of TN and TP concentrations were mapped. The
      integrative comparisons of semivariogram parameters with different trends to the
      kriging prediction errors of TN and TP indicated that the two-order trend is
      preferable. Kriging SDs provided valuable information that will increase the
      accuracy of TN and TP mapping. The probability kriging method is useful to assess
      the risk of N and P pollution by providing the conditional probability of N and P
      concentrations exceeding the threshold concentrations of 3.2 and 1.05 g/kg,
      respectively. The probability distribution of TN and TP at different levels will
      be helpful to conduct risk assessment, optimize fertilization, and control the
      pollution of N and P.

PMID- 17526873
TI  - Prediction of radionuclide aging in soils from the Chernobyl and Mediterranean
      areas.
AB  - The aging of soil-pollutant interaction, which may lead to an increase in
      pollutant fixation, is the main driving force in the natural attenuation of
      contaminated soils. Here a test was evaluated to predict the aging of
      radiostrontium and radiocesium in soils from the Chernobyl and Mediterranean
      areas. After contamination, soils were maintained at various temperatures for up
      to 12 mo, with or without drying-wetting (DW) cycles. Changes in the quantity of
      radionuclide reversibly sorbed over time were monitored using an extraction test
      (1 mol L(-1) NH(4)Cl; 10 mL g(-1); 16 h). The fixed fraction could not be
      predicted from soil properties controlling the sorption step. Aging was not as
      relevant for Sr as for Cs. The time elapsed since contamination was the main
      factor responsible for the slight (up to 1.3-fold) decreases in Sr extraction
      yields. The additional effect of DW cycles was negligible. Instead, all factors
      accelerated Cs aging due to the enhancement of Cs trapping by clay interlayer
      collapse, with up to 20-fold increases in Cs fixation. The DW cycles also caused
      secondary effects on the Cs-specific sorption pool, which were beneficial or
      detrimental depending on the soil type. Extraction yields from laboratory aged
      samples agreed with those from field samples taken a few years after the
      Chernobyl accident. These results confirm the prediction capacity of the
      laboratory test and its usefulness in risk assessment exercises and in the design
      of intervention actions, particularly because neither fixation nor aging were
      related to the soil properties, such as clay content.

PMID- 17526874
TI  - Monitoring of nitrate leaching in sandy soils: comparison of three methods.
AB  - Proper N fertilizer and irrigation management can reduce nitrate leaching while
      maintaining crop yield, which is critical to enhance the sustainability of
      vegetable production on soils with poor water and nutrient-holding capacities.
      This study evaluated different methods to measure nitrate leaching in mulched
      drip-irrigated zucchini, pepper, and tomato production systems. Fertigation rates
      were 145 and 217 kg N ha(-1) for zucchini; 192 and 288 kg N ha(-1) for pepper;
      and 208 and 312 kg N ha(-1) for tomato. Irrigation was either applied at a fixed
      daily rate or based on threshold values of soil moisture sensors placed in
      production beds. Ceramic suction cup lysimeters, subsurface drainage lysimeters
      and soil cores were used to access the interactive effects of N rate and
      irrigation management on N leaching. Irrigation treatments and N rate interaction
      effects on N leaching were significant for all crops. Applying N rates in excess
      of standard recommendations increased N leaching by 64, 59, and 32%,
      respectively, for pepper, tomato, and zucchini crops. Independent of the
      irrigation treatment or nitrogen rate, N leaching values measured from the
      ceramic cup lysimeter-based N leaching values were lower than the values from the
      drainage lysimeter and soil coring methods. However, overall nitrate
      concentration patterns were similar for all methods when the nitrate
      concentration and leached volume were relatively low.

PMID- 17526875
TI  - Riparian plant material inputs to the Murray River, Australia: composition,
      reactivity, and role of nutrients.
AB  - By changing riparian plants from Eucalypts to pasture and exotic deciduous trees,
      modern development has altered the type of carbon assimilated by Australian
      rivers. To investigate influences of plant litter substrates on biochemical
      oxygen demand, plant materials entering the Murray River were analyzed for their
      composition and mineralization potential. Plant materials were distinguished
      compositionally by two principal components, structural carbon and
      macronutrients, as: (i) Eucalyptus leaves, (ii) Eucalyptus bark and Casuarina
      cunninghamiana seed cone, (iii) grasses, (iv) macrophytes, (v) aquatic herbs,
      (vi) non-eucalypt leaf (Salix, Casuarina, Acacia). Ratios of C/P (1879-14524) and
      C/N (65-267) were relatively high in Eucalyptus bark, while mean N/P (7-60)
      ratios were similar among plant materials. Terrestrial weathering increased C/P
      and C/N ratios, while N/P ratios remained similar, due to greater loss of N and P
      relative to C. Aerobic decay experiments showed that nutrient supplementation
      accelerated decay of all organic substrates, except for grasses that decayed
      efficiently without supplementation. Aquatic herbs also had substantial carbon
      availability, macrophytes and non-eucalypt leaves had intermediate carbon
      availability, while eucalypt leaf and bark had intermediate to low carbon
      availabilities. Because biochemical oxygen demand varies with organic substrates
      sampled from the Murray River, and also with soluble nutrient availability, it is
      plausible that that modern changes to riverine plant communities and land use
      have influenced the biogeochemistry of this river toward faster, and more
      complete, processing of allochthonous carbon.

PMID- 17526876
TI  - Agri-environmental thresholds using Mehlich III soil phosphorus saturation index
      for vegetables in histosols.
AB  - The P concentration in Norton Creek which drains cultivated Histosols in Quebec
      showed median concentration exceeding up to 14 times the environmental guideline
      of 0.03 mg total P L(-1). The aim of this study was to develop environmental and
      agronomic thresholds using soil tests to provide a tool for P management in
      Histosols. Soil samples were collected from Histosols across Quebec (82) and in
      fertilizer trials (66) to calibrate soil test methods against the degree of P
      saturation (DPS(OX)) using the acid-oxalate method and setting alpha(m) = 0.4,
      and the water-extractable P (P(W)) (Sissingh, 1971). The field trials on crop
      response to added P were conducted with carrots (8), potatoes (11), onions (10),
      Chinese cabbage (7), celery (10), and lettuce (20). Relative yields were computed
      as yield in control without P divided by highest yield with added P. The Mehlich
      III (M-III) P extraction was more closely related (r(2) = 0.73) to DPS(OX) than
      the Bray 1 method (r(2) = 0.62) and the Florida extraction method (r(2) = 0.53).
      The [P/(Al+gammaFe)](M-III) ratio as index of P saturation (IPS(M-III)) was the
      most closely related to DPS(OX) (r(2) = 0.88) setting gamma = 5. The critical
      [P/(Al+5Fe)](M-III) ratio of 0.05 at DPS(OX) = 0.25 and P(W) = 9.7 mg P L(-1) was
      validated by an independent study from North Carolina. The soil group (low- vs.
      high-IPS(M-III) soils) significantly influenced crop response to added P.
      Critical agronomic IPS(M-III) values were found between 0.10 and 0.15. Those
      environmental and agronomic benchmarks are instrumental for managing the P in
      vegetable-grown Histosols.

PMID- 17526877
TI  - Test of APEX for nine forested watersheds in East Texas.
AB  - Hydrologic/water quality models are increasingly used to explore management and
      policy alternatives for managing water quality and quantity from intensive
      silvicultural practices with best management practices (BMPs) in forested
      watersheds due to the limited number of and cost of conducting watershed
      monitoring. The Agricultural Policy/Environmental eXtender (APEX) model was field
      tested using 6 yr of data for flow, sediment, nutrient, and herbicide losses
      collected from nine small (2.58 to 2.74 ha) forested watersheds located in
      southwest Cherokee County in East Texas. Simulated annual average stream flow for
      each of the nine watersheds was within +/- 7% of the corresponding observed
      values; simulated annual average sediment losses were within +/- 8% of measured
      values for eight out of nine watersheds. Nash-Sutcliffe efficiency (EF) values
      ranged from 0.68 to 0.94 based on annual stream flow comparison and from 0.60 to
      0.99 based on annual sediment comparison. Similar to what was observed, simulated
      flow, sediment, organic N, and P were significantly increased on clear-cut
      watersheds compared with the control watersheds. APEX reasonably simulated
      herbicide losses, with an EF of 0.73 and R(2) of 0.74 for imazapyr, and EF of
      0.65 and R(2) of 0.68 for hexazinone based on annual values. Overall, the results
      show that APEX was able to predict the effects of silvicultural practices with
      BMPs on water quantity and quality and that the model is a useful tool for
      simulating a variety of responses to forest conditions.

PMID- 17526878
TI  - Modeling riverine nitrate export from an East-Central Illinois watershed using
      SWAT.
AB  - Reliable water quality models are needed to forecast the water quality
      consequences of different agricultural nutrient management scenarios. In this
      study, the Soil and Water Assessment Tool (SWAT), version 2000, was applied to
      simulate streamflow, riverine nitrate (NO(3)) export, crop yield, and watershed
      nitrogen (N) budgets in the upper Embarras River (UER) watershed in east-central
      Illinois, which has extensive maize-soybean cultivation, large N fertilizer
      input, and extensive tile drainage. During the calibration (1994-2002) and
      validation (1985-1993) periods, SWAT simulated monthly and annual stream flows
      with Nash-Sutcliffe coefficients (E) ranging from 0.67 to 0.94 and R(2) from 0.75
      to 0.95. For monthly and annual NO(3) loads, E ranged from -0.16 to 0.45 and R(2)
      from 0.36 to 0.74. Annual maize and soybean yields were simulated with relative
      errors ranging from -10 to 6%. The model was then used to predict the changes in
      NO(3) output with N fertilizer application rates 10 to 50% lower than original
      application rates in UER. The calibrated SWAT predicted a 10 to 43% decrease in
      NO(3) export from UER and a 6 to 38% reduction in maize yield in response to the
      reduction in N fertilizer. The SWAT model markedly overestimated NO(3) export
      during major wet periods. Moreover, SWAT estimated soybean N fixation rates
      considerably greater than literature values, and some simulated changes in the N
      cycle in response to fertilizer reduction seemed to be unrealistic. Improving
      these aspects of SWAT could lead to more reliable predictions in the water
      quality outcomes of nutrient management practices in tile-drained watersheds.

PMID- 17526879
TI  - Occurrence and bioavailability of pyrethroids in a mixed land use watershed.
AB  - The shift in land use patterns within many urban areas has the potential to
      influence the magnitude and nature of nonpoint-source pollution. The presence of
      pyrethroid insecticides in urban surface streams is of particular concern due to
      the broad spectrum toxicity of pyrethroids to aquatic organisms and the
      widespread use of pyrethroid products for agricultural and urban pest control.
      Sediment samples were collected throughout a mixed land use watershed in southern
      California during two sampling periods and analyzed for a suite of pyrethroids.
      Bifenthrin and fenpropathrin were found most frequently in the sediment samples,
      with the highest concentrations associated with sites adjacent to large
      commercial nurseries. Sediments from residential areas or residential-commercial
      mixed areas had fewer detections and significantly lower concentrations than the
      nursery runoff sediments. No apparent difference was found between wet and dry
      season concentrations, which may be attributed to the fact that the lack of flow
      under dry weather conditions rendered pyrethroid residues immobile. Organic
      carbon-normalized sediment concentrations were poorly correlated with the freely
      dissolved pore water concentrations measured by solid phase microextraction
      (SPME), suggesting factors other than sediment organic carbon content should be
      considered when relating concentrations to potential toxicities.

PMID- 17526880
TI  - Runoff water quality from turfgrass established using volume-based composted
      municipal biosolids applications.
AB  - Municipal programs for turfgrass establishment recommend large volume-based
      application rates of composted municipal biosolids (CMB). This study compared
      runoff water quality among combinations of two common turfgrass establishment
      practices and two CMB sources. Bryan- or Austin-CMB were incorporated into 5 cm
      of soil at a rate of 12.5 or 25% by volume (v/v) on an 8.5% slope. Tifway
      bermudagrass [Cynodon dactylon (L.) Pers. x C. transvaalensis Burtt-Davy, var.
      Tifway] sprigs were planted and established; sod, produced at a separate site
      using either CMB amendment at the 25% v/v rate, was transplanted to the runoff
      plots on the same day. A mature stand of bermudagrass was used as a control.
      Runoff water was collected after each of eight natural rain events during the
      sampling period. Total runoff water loss (mm) was similar for the CMB-amended
      sprigged and transplanted sod stands. The concentration of total dissolved P
      (TDP) in runoff water was greatest from the transplanted sod in the first seven
      rain events (4.1 to 7.5 mg L(-1)). The concentration of TDP in runoff water was
      similar at both the 12.5 and 25% v/v incorporation rates. Regression analysis
      indicated Mehlich-3-extractable soil test P concentrations in soil amended with
      CMB were positively correlated to concentration and mass loss of dissolved P in
      runoff. At similar application rates, dissolved P loss in runoff water was
      reduced by incorporating CMB into the soil on site rather than transplanting sod
      produced with CMB.

PMID- 17526881
TI  - Nutrient load generated by storm event runoff from a golf course watershed.
AB  - Turf, including home lawns, roadsides, golf courses, parks, etc., is often the
      most intensively managed land use in the urban landscape. Substantial inputs of
      fertilizers and water to maintain turf systems have led to a perception that turf
      systems are a major contributor to nonpoint source water pollution. The primary
      objective of this study was to quantify nutrient (NO(3)-N, NH(4)-N, and PO(4)-P)
      transport in storm-generated surface runoff from a golf course. Storm event
      samples were collected for 5 yr (1 Apr. 1998-31 Mar. 2003) from the Morris
      Williams Municipal Golf Course in Austin, TX. Inflow and outflow samples were
      collected from a stream that transected the golf course. One hundred fifteen
      runoff-producing precipitation events were measured. Median NO(3)-N and PO(4)-P
      concentrations at the outflow location were significantly (p < 0.05) greater than
      like concentrations measured at the inflow location; however, median outflow
      NH(4)-N concentration was significantly less than the median inflow
      concentration. Storm water runoff transported 1.2 kg NO(3)-N ha(-1) yr(-1), 0.23
      kg NH(4)-N ha(-1) yr(-1), and 0.51 kg PO(4)-P ha(-1) yr(-1) from the course.
      These amounts represent approximately 3.3% of applied N and 6.2% of applied P
      over the contributing area for the same period. NO(3)-N transport in storm water
      runoff from this course does not pose a substantial environmental risk; however,
      the median PO(4)-P concentration exiting the course exceeded the USEPA
      recommendation of 0.1 mg L(-1) for streams not discharging into lakes. The PO(4)
      P load measured in this study was comparable to soluble P rates measured from
      agricultural lands. The findings of this study emphasize the need to balance golf
      course fertility management with environmental risks, especially with respect to
      phosphorus.

PMID- 17526882
TI  - Use of wastewater and compost extracts as nutrient sources for growing nursery
      and turfgrass species.
AB  - Nutrient salts present in liquid by-products following waste treatment are lost
      resources if not effectively recycled, and can cause environmental problems if
      improperly disposed. This research compared the growth response and mineral
      nutrient status of two nursery and two turfgrass species, hydroponically supplied
      with nutritive by-product extracts derived from anaerobically digested municipal
      solid waste (MSW) and aerobically composted organic wastes from the mushroom and
      MSW industries. Forsythia (Forsythia x intermedia 'Lynwood') and weigela (Weigela
      florida 'Red Prince'), and creeping bentgrass (Agrostis palustris Huds.) and
      Kentucky bluegrass (Poa pratensis L.), were grown in nutrient solutions/extracts
      prepared from: (i) half-strength Hoagland's #2 solution (HH; control), (ii) Plant
      Products liquid fertilizer (PP; g kg(-1): 180 N; 39 P; 224 K), (iii) spent
      mushroom compost (SMC), (iv) MSW compost (GMC), and (v) intra-process wastewater
      from the anaerobic digestion of MSW (ADW). Additional nutrient solutions (SMC-A,
      GMC-A, and ADW-A) were prepared by amending the original solutions with N, P,
      and/or K to concentrations in HH (mg L(-1): 105 N; 15 P; 118 K). Plants receiving
      the SMC-A extract grew best or at least as well as those in HH, PP, and the
      amended GMC-A and ADW-A solutions. This study indicated that, with proper
      amendments of N, P, K and other nutrients, water-soluble constituents derived
      from organic waste treatment have potential for use as supplemental nutrient
      sources for plant production.

PMID- 17526883
TI  - Phosphorus and other soil components in a dairy effluent sprayfield within the
      central Florida Ridge.
AB  - There is concern that P from dairy effluent sprayfields will leach into
      groundwater beneath Suwannee River basins in northern Florida. Our purpose was to
      describe the effects of dairy effluent irrigation on the movement of soil P and
      other nutrients within the upper soil profile of a sprayfield over three 12-mo
      cycles (April 1998-March 2001). Effluent P rates of 70, 110, and 165 kg ha(-1)
      cycle(-1) were applied to forages that were grown year-round. The soil is a deep,
      excessively drained sand (thermic, uncoated Typic Quartzipsamment). Mean P
      concentration in soil water below the rooting zone (152-cm depth) was < or = 0.1
      mg L(-1) during 11 3-mo periods. Mehlich-1-extractable (M1) P, Al, and Ca in the
      topsoil increased over time but did not change in subsoil depths of 25 to 51, 51
      to 71, 71 to 97, and 97 to 122 cm. Topsoil Ca increased as effluent rate
      increased. High Ca levels were found in dairy effluent (avg.: 305 mg L(-1)) and
      supplemental irrigation water (avg.: 145 mg L(-1)) which likely played a role in
      retaining P in the topsoil. An effect of effluent rate on P and Al concentrations
      in the topsoil was not detected, probably due to large and variable quantities
      present at project initiation. The P retention capacity (i.e., Al plus Fe)
      increased in the topsoil because Al increased. Dairy effluent contained Al (avg.:
      31 mg L(-1)). Phosphorus saturation ratio (PSR) increased over time in the
      topsoil but not in subsoil layers. Regardless of effluent rate, the P retention
      capacity and PSR of subsoil, which contained 119 to 229 mg kg(-1) of Al, should
      be taken into account when assessing the risk of P moving below the rooting zone
      of most forage crops.

PMID- 17526884
TI  - Role of organic matter in microbial transport during irrigation with sewage
      effluent.
AB  - Reduction of migration of fecal coliforms (FC) and streptococci (FS) by limiting
      the leaching in effluent-irrigated soil was tested in lysimeters packed with
      quartz sand without or with added biosolids compost or with one of two clayey
      soils. The 200-L, 70-cm-deep lysimeters were either planted with a Eucalyptus
      camaldulensis or an Oroblanco citrus tree (in the sand only), or not planted. The
      Eucalyptus was irrigated with oxidation pond effluent (OPE) and the Oroblanco
      with mechanical-biological treatment plant effluent (MBTPE). The leaching
      fraction (LF) ranged from 0.2 to about 1.0, and the residence time (RT) from
      under 1 to 40 d. The Eucalyptus was also tested under intermittent leaching (RT
      11-20 d) and deficit irrigation (without leaching for about 6 mo) regimes. Under
      MBTPE irrigation there was little or no leaching of FC and FS. Under OPE
      irrigation at LF 1 without a Eucalyptus there was little or no bacterial leaching
      at irrigation rates below 40 L d(-1) per lysimeter (RT > or = 0.8 d). Bacterial
      counts in the leachate were substantial in the presence of a Eucalyptus tree
      under LF 0.2 and intermittent leaching regimes, and when sand-packed unplanted
      lysimeters received OPE effluent at >45 L d(-1). Bacterial recovery peaked at LF
      0.2, at up to 45% of the input level. At LF 1 (RT 0.6-2.8 d) and with
      intermittent leaching the recoveries were minute. Bacterial counts in the washout
      from the deficit-irrigated lysimeters were typical of nonpolluted soils. The
      bacterial concentration and recovery patterns in the leachate mostly matched the
      organic carbon (OC) load in the irrigation water, and its concentration and
      bioavailablity in the leachate. We related the leaching patterns of the fecal
      bacteria to their relative reproduction and die-off rates, and to the dependence
      of their regrowth on available carbon sources.

PMID- 17526885
TI  - Environmental impact evaluation of feeds prepared from food residues using life
      cycle assessment.
AB  - There is increasing concern about feeds prepared from food residues (FFR) from an
      environmental viewpoint; however, various forms of energy are consumed in the
      production of FFR. Environmental impacts of three scenarios were therefore
      investigated and compared using life cycle assessment (LCA): production of liquid
      FFR by sterilization with heat (LQ), production of dehydrated FFR by dehydration
      (DH), and disposal of food residues by incineration (IC). The functional unit was
      defined as 1 kg dry matter of produced feed standardized to a fixed energy
      content. The system boundaries included collection of food residues and
      production of feed from food residues. In IC, food residues are incinerated as
      waste, and thus the impacts of production and transportation of commercial
      concentrate feeds equivalent to the FFR in the other scenarios are included in
      the analysis. Our results suggested that the average amounts of greenhouse gas
      (GHG) emissions from LQ, DH, and IC were 268, 1073, and 1066 g of CO(2)
      equivalent, respectively. The amount of GHG emissions from LQ was remarkably
      small, indicating that LQ was effective for reducing the environmental impact of
      animal production. Although the average amount of GHG emissions from DH was
      nearly equal to that from IC, a large variation of GHG emissions was observed
      among the DH units. The energy consumption of the three scenarios followed a
      pattern similar to that of GHG emissions. The water consumption of the FFR
      producing units was remarkably smaller than that of IC due to the large volumes
      of water consumed in forage crop production.

PMID- 17526886
TI  - Removal of perchlorate from contaminated waters using surfactant-modified
      zeolite.
AB  - We investigated the potential of using surfactant (hexadecyltrimethylammonium)
      modified zeolite (SMZ) as an inexpensive sorbent for removing perchlorate
      (ClO(4)(-)) from contaminated waters in the presence of competing anions. In
      batch systems, the presence of 10 mM OH(-) (i.e., pH 12), CO(3)(2-), Cl(-), or
      SO(4)(2-) had little effect on the sorption of ClO(4)(-) by SMZ, indicating that
      the sorption of ClO(4)(-) by SMZ was very selective. The presence of 10 mM NO(3)(
      ), however, reduced the sorption of ClO(4)(-) at low initial concentrations. The
      maximum sorption capacity for ClO(4)(-) by the SMZ remained relatively constant
      (40-47 mmol kg(-1)), in the absence or presence of the competing ions. In flow
      through systems, ClO(4)(-) broke through the SMZ columns much later than other
      anions present in an artificial ground water. The affinity of the anions for SMZ
      followed the sequence of ClO(4)(-) > > NO(3)(-) > SO(4)(2-) > Cl(-). Perchlorate
      loading under dynamic flow-through conditions was 34 mmol kg(-1), somewhat less
      than the maximum loading of 40 to 47 mmol kg(-1) determined by the batch method.
      Less than 1% of previously sorbed ClO(4)(-) was leached out by ultra-pure water,
      by extraction fluid #1 of the standard toxicity characteristic leaching procedure
      (TCLP), or by a solution of 0.28 M Na(2)CO(3)/0.5 M NaOH. About 40% of the
      previously sorbed ClO(4)(-) was leached out from SMZ by a 0.5 M NO(3)(-)
      solution. The exchange of ClO(4)(-) with NO(3)(-) corroborated results of the
      batch tests where NO(3)(-) was shown to compete with ClO(4)(-) sorption.

PMID- 17526887
TI  - Lability of drinking water treatment residuals (WTR) immobilized phosphorus:
      aging and pH effects.
AB  - Time constraints associated with conducting long-term (>20 yr) field experiments
      to test the stability of drinking water treatment residuals (WTR) sorbed
      phosphorus (P) inhibit improved understanding of the fate of sorbed P in soils
      when important soil properties (e.g., pH) change. We used artificially aged
      samples to evaluate aging and pH effects on lability of WTR-immobilized P.
      Artificial aging was achieved through incubation at elevated temperatures (46 or
      70 degrees C) for 4.5 yr, and through repeated wetting and drying for 2 yr. Using
      a modified isotopic ((32)P) dilution technique, coupled with a stepwise
      acidification procedure, we monitored changes in labile P concentrations over
      time. This technique enabled evaluation of the effect of pH on the lability of
      WTR-immobilized P. Within the pH range of 4 to 7, WTR amendment, coupled with
      artificial aging, ultimately reduced labile P concentrations by > or = 75%
      relative to the control (no-WTR) samples. Soil samples with different
      physicochemical properties from two 7.5-yr-old, one-time WTR-amended field sites
      were utilized to validate the trends observed with the artificially aged samples.
      Despite the differences in physicochemical properties among the three (two field
      aged and one artificially aged) soil samples, similar trends of aging and pH
      effects on lability of WTR-immobilized P were observed. Labile P concentrations
      of the WTR-amended field-aged samples of the two sites decreased 6 mo after WTR
      amendment and the reduction persisted for 7.5 yr, ultimately resulting in > or =
      70% reduction, compared to the control plots. We conclude that WTR application is
      capable of reducing labile P concentration in P-impacted soils, doing so for a
      long time, and that within the commonly encountered range of pH values for
      agricultural soils WTR-immobilized P should be stable.

PMID- 17526888
TI  - Comparison of phosphorus forms in wet and dried animal manures by solution
      phosphorus-31 nuclear magnetic resonance spectroscopy and enzymatic hydrolysis.
AB  - Both enzymatic hydrolysis and solution (31)P nuclear magnetic resonance (NMR)
      spectroscopy have been used to characterize P compounds in animal manures. In
      this study, we comparatively investigated P forms in 0.25 M NaOH/0.05 M EDTA
      extracts of dairy and poultry manures by the two methods. For the dairy manure,
      enzymatic hydrolysis revealed that the majority of extracted P was inorganic P
      (56%), with 10% phytate-like P, 9% simple monoester P, 6% polynucleotide-like P,
      and 18% non-hydrolyzable P. Similar results were obtained by NMR spectroscopy,
      which showed that inorganic P was the major P fraction (64-73%), followed by 6%
      phytic acid, 14 to 22% other monoesters, and 7% phosphodiesters. In the poultry
      manure, enzymatic hydrolysis showed that inorganic P was the largest fraction
      (71%), followed by 15% phytate-like P and 1% other monoesters, and 3%
      polynucleotide-like P. NMR spectroscopy revealed that orthophosphate was 51 to
      63% of extracted P, phytic acid 24 to 33%, other phosphomonoesters 6 to 12%, and
      phospholipids and DNA 2% each. Drying process increased orthophosphate (8.4% of
      total P) in dairy manure, but decreased orthophosphate (13.3% of total P) in
      poultry manure, suggesting that drying treatment caused the hydrolysis of some
      organic P to orthophosphate in dairy manure, but less recovery of orthophosphate
      in poultry manure. Comparison of these data indicates that the distribution
      patterns of major P forms in animal manure determined by the two methods were
      similar. Researchers can utilize the method that best fits their specific
      research goals or use both methods to obtain a full spectrum of manure P
      characterization.

PMID- 17526889
TI  - Spatial variation of soil phosphorus within a drainage ditch network.
AB  - Agricultural drainage ditches serve as P transport pathways from fields to
      surface waters. Little is known about the spatial variation of P at the soil
      water interface within ditch networks. We quantified the spatial variation of
      surficial (0-5 cm) soil P within vegetated agricultural ditches on a farm in
      Princess Anne, MD with an approximately 30-yr history of poultry litter
      application. Ditch soils from 10 ditches were sampled at 10-m intervals and
      analyzed for acid ammonium oxalate-extractable P, Fe, Al (P(ox), Fe(ox), Al(ox)),
      and pH. These variables were spatially autocorrelated. Oxalate-P (min = 135 mg
      kg(-1), max = 6919 mg kg(-1), mean = 700 mg kg(-1)) exhibited a high standard
      deviation across the study area (overall 580 mg kg(-1)) and within individual
      ditches (maximum 1383 mg kg(-1)). Several ditches contained distinct areas of
      high P(ox), which were associated with either point- or nonpoint-P sources.
      Phosphorus was correlated with Al(ox) or Fe(ox) within specific ditches. Across
      all ditches, Al(ox) (r = 0.80; p < 0.001) was better correlated with P(ox) than
      was Fe(ox) (r = 0.44; p < 0.001). The high level of spatial variation of soil P
      observed in this ditch network suggests that spatially distributed sampling may
      be necessary to target best management practices and to model P transport and
      fate in ditch networks.

PMID- 17526890
TI  - Spatial analysis of a large magnitude erosion event following a Sierran wildfire.
AB  - High intensity wildfire due to long-term fire suppression and heavy fuels buildup
      can render watersheds highly susceptible to wind and water erosion. The 2002
      "Gondola" wildfire, located just southeast of Lake Tahoe, NV-CA, was followed 2
      wk later by a severe hail and rainfall event that deposited 7.6 to 15.2 mm of
      precipitation over a 3 to 5 h time period. This resulted in a substantive upland
      ash and sediment flow with subsequent down-gradient riparian zone deposition.
      Point measurements and ESRI ArcView were applied to spatially assess source area
      contributions and the extent of ash and sediment flow deposition in the riparian
      zone. A deposition mass of 380 Mg of ash and sediment over 0.82 ha and pre
      wildfire surface bulk density measurements were used in conjunction with two
      source area assessments to generate an estimation of 10.1 mm as the average depth
      of surface material eroded from the upland source area. Compared to previous
      measurements of erosion during rainfall simulation studies, the erosion of 1800
      to 6700 g m(-2) mm(-1) determined from this study was as much as four orders of
      magnitude larger. Wildfire, followed by the single event documented in this
      investigation, enhanced soil water repellency and contributed 17 to 67% of the
      reported 15 to 60 mm ky(-1) of non-glacial, baseline erosion rates occurring in
      mountainous, granitic terrain sites in the Sierra Nevada. High fuel loads now
      common to the Lake Tahoe Basin increase the risk that similar erosion events will
      become more commonplace, potentially contributing to the accelerated degradation
      of Lake Tahoe's water clarity.

PMID- 17526891
TI  - Functional requirements of the yellow fever virus capsid protein.
AB  - Although it is known that the flavivirus capsid protein is essential for genome
      packaging and formation of infectious particles, the minimal requirements of the
      dimeric capsid protein for virus assembly/disassembly have not been
      characterized. By use of a trans-packaging system that involved packaging a
      yellow fever virus (YFV) replicon into pseudo-infectious particles by supplying
      the YFV structural proteins using a Sindbis virus helper construct, the
      functional elements within the YFV capsid protein (YFC) were characterized.
      Various N- and C-terminal truncations, internal deletions, and point mutations of
      YFC were analyzed for their ability to package the YFV replicon. Consistent with
      previous reports on the tick-borne encephalitis virus capsid protein, YFC
      demonstrates remarkable functional flexibility. Nearly 40 residues of YFC could
      be removed from the N terminus while the ability to package replicon RNA was
      retained. Additionally, YFC containing a deletion of approximately 27 residues of
      the C terminus, including a complete deletion of C-terminal helix 4, was
      functional. Internal deletions encompassing the internal hydrophobic sequence in
      YFC were, in general, tolerated to a lesser extent. Site-directed mutagenesis of
      helix 4 residues predicted to be involved in intermonomeric interactions were
      also analyzed, and although single mutations did not affect packaging, a YFC with
      the double mutation of leucine 81 and valine 88 was nonfunctional. The effects of
      mutations in YFC on the viability of YFV infection were also analyzed, and these
      results were similar to those obtained using the replicon packaging system, thus
      underscoring the flexibility of YFC with respect to the requirements for its
      functioning.

PMID- 17526892
TI  - An ELISA for apolipoprotein M reveals a strong correlation to total cholesterol
      in human plasma.
AB  - Apolipoprotein M (apoM) is a 188 amino acid, 25 kDa protein belonging to the
      lipocalin protein superfamily. Although predominantly associated with high
      density lipoprotein, apoM is found in all major lipoprotein classes. To
      facilitate clinical studies of apoM, we have developed a sandwich ELISA for the
      measurement of apoM in human plasma. This method has been used to investigate
      normal apoM variation and to establish reference values for healthy individuals
      through the measurement of 598 samples from the Nordic Reference Interval Project
      Bio-bank and Database (NOBIDA) biobank. For women 18-49 years old, the reference
      interval for apoM was 0.58-1.18 micromol/l, whereas for women 50+ years and for
      men, the reference range was 0.61-1.30 micromol/l. Correlation studies of apoM
      with 26 common clinical chemical analytes from the NOBIDA database revealed a
      marked positive correlation with plasma total cholesterol (r = 0.52) and LDL and
      HDL cholesterol (r = 0.43 and 0.36, respectively). There was no statistically
      significant correlation with HDL/total cholesterol ratio or body mass index. In
      conclusion, a sandwich ELISA for the measurement of apoM in human plasma shows
      that apoM concentration is strongly correlated to total cholesterol in healthy
      individuals.

PMID- 17526893
TI  - Efficacy of trapping during the initial proactive culls in the randomised badger
      culling trial.
AB  - The randomised badger culling trial (RBCT) has shown that widespread badger
      culling in predefined areas of approximately 100 km2 led to a reduction in the
      number of cattle herds testing positive for bovine tuberculosis (TB) ('herd
      breakdowns'), but was associated with an increase in cattle tb in surrounding
      areas. This study has tried to estimate the trapping efficacy and the level of
      reduction of the badger population during the initial proactive culls in the
      RBCT. For seven triplets trapping efficacy was estimated between 71 per cent and
      85 per cent, and for three triplets between 35 per cent and 46 per cent. Two of
      the latter triplets had trapping coinciding with harsh climatic conditions.
      Badger population removal was estimated at 64 per cent to 77 per cent in the
      former and 32 per cent to 39 per cent in the latter triplets. In most of the
      treatment areas there was therefore a consistent and substantial reduction in the
      number of badgers at the end of the initial cull. All the proactive treatment
      areas were subjected to further culls, and it is therefore likely that greater
      reductions would have occurred by the end of 2005, when the analysis of cattle
      herd breakdowns took place.

PMID- 17526894
TI  - Serological survey for antibodies against pestiviruses in sheep in Austria.
AB  - The prevalence of antibodies to pestiviruses was investigated in 4931 sheep, in
      377 flocks, in four federal states of Austria, by means of an indirect elisa that
      detected antibodies to Border disease virus (BDV) and bovine viral diarrhoea
      virus (BVDV). The mean flock prevalence was 62.9 per cent and the mean individual
      prevalence was 29.4 per cent. Comparative neutralisation studies on the elisa
      positive samples with BVDV type 1 (BVDV-1), BVDV type 2 (BVDV-2) and BDV recorded
      336 samples with higher titres (more than four times average) to BVDV-1, three
      samples with higher titres to BVDV-2 and 55 samples with higher titres to BDV.
      The other samples did not show clear differences in antibody titres against the
      strains of pestivirus tested because of cross-reactions. The seroprevalence of
      pestiviruses in sheep was significantly higher on farms with cattle. There were
      significant regional differences between the prevalences in flocks and individual
      sheep, the highest prevalences being in the region of Austria where communal
      alpine pasturing of sheep, goats and cattle is an important part of farming.

PMID- 17526895
TI  - Effect of acepromazine on the signs of capture stress in captive and free-ranging
      roe deer (Capreolus capreolus).
AB  - The differences between the capture stress responses of captive and free-ranging
      roe deer (Capreolus capreolus) and their modulation by acepromazine, during a
      period of three hours' physical restraint after capture in drive-nets, were
      examined in 16 free-ranging and 16 captive roe deer. Eight of the free-ranging
      and eight of the captive animals received acepromazine intramuscularly, and the
      other eight free-ranging and eight captive deer received the same volume of
      saline. Heart rate, body temperature and haematological and serum biochemical
      parameters were analysed. In the groups treated with acepromazine, the heart rate
      stabilised sooner, and the red blood cell (RBC) count, haemoglobin concentration,
      packed-cell volume, the serum activities of creatine kinase (CK), aspartate
      aminotransferase (AST), alanine aminotransferase (ALT) and lactate dehydrogenase
      (LDH) and the concentrations of creatinine and lactate were significantly lower,
      and serum glucose started to decrease earlier, than in the untreated groups.
      Serum potassium levels decreased over time only in the untreated groups. The body
      temperature stabilised earlier, and the RBC count, haemoglobin concentration,
      serum CK, AST, ALT and LDH activities, and serum creatinine, lactate, cholesterol
      and glucose concentrations were significantly lower in the free-ranging roe deer
      than in the captive deer.

PMID- 17526896
TI  - Seroprevalence of BVDV in cattle of different ages on 17 dairy farms in western
      England.

PMID- 17526897
TI  - Unilateral ovariectomy and cystectomy due to multiple ovarian cysts with
      subsequent pregnancy in a Belgian shepherd dog.

PMID- 17526898
TI  - Working with the insurance industry.

PMID- 17526899
TI  - Attitudes towards badger culling.

PMID- 17526900
TI  - Hunt for a second copper toxicosis gene.

PMID- 17526901
TI  - Investigating scent marking in dogs.

PMID- 17526902
TI  - Intubating rabbits.

PMID- 17526903
TI  - Diagnosis of fog fever.

PMID- 17526904
TI  - Changes in systolic left ventricular function in isolated mitral regurgitation. A
      strain rate imaging study.
AB  - AIMS: The aim of the present study is to understand the changes in left
      ventricular (LV) regional systolic deformation based on strain rate (SR) imaging
      in patients with isolated mitral regurgitation (MR). Progressive LV dilatation
      and irreversible myocardial damage as a result of chronic isolated MR are
      important causes of morbidity and mortality in patients following valve surgery.
      To date, there is no specific diagnostic method to detect subclinical changes in
      systolic function before irreversible dysfunction occurs. METHODS AND RESULTS:
      Seventy-seven individuals were studied: 54 asymptomatic patients (age 56 +/- 12)
      with isolated non-ischaemic MR divided into three groups: mild, moderate, and
      severe and 23 healthy subjects. All underwent a standard echo examination and a
      tissue Doppler study. A mathematical study was carried out to predict how SR
      should alter with increasing dimensions and due to irreversible myocardial
      damage. Radial as well as longitudinal peak systolic SR was significantly
      decreased in patients with severe MR compared to the other groups (LV posterior
      wall: P = 0.0006, septum: P = 0.0004, LV lateral wall: P = 0.0003). From both
      modelling and in our patients, deformation correlated inversely with LV end
      diastolic diameter and end-systolic diameter (ESD). Deformation measurements
      (corrected for increased geometry) enabled the identification of patients
      classically referred to as at risk of irreversible myocardial damage (ESD > or =
      4.5 cm). CONCLUSION: In patients with a wide range of MR, deformation remains
      unchanged due to a balance of increased dimensions and increased stroke volume.
      Only when contractility is expected to change, deformation will significantly
      decrease. SR imaging indices, corrected for geometry, might potentially be useful
      in detecting subclinical deterioration in LV function in asymptomatic patients
      with severe MR.

PMID- 17526905
TI  - Detection of recent myocardial ischaemia by molecular imaging of P-selectin with
      targeted contrast echocardiography.
AB  - AIMS: We hypothesized that molecular imaging of endothelial P-selectin expression
      with targeted myocardial contrast echocardiography (MCE) could identify recently
      ischaemic myocardium without infarction. METHODS AND RESULTS: The microvascular
      behaviour of P-selectin-targeted (MB(p)) and control (MB(c)) microbubbles was
      assessed by intravital microscopy of the cremaster muscle in mice. Targeted MCE
      imaging with MB(p) and MB(c) was performed in mice after brief left anterior
      descending (LAD) occlusion and reperfusion and in open- and closed-chest
      controls. Regional wall motion and perfusion by MCE were assessed during
      occlusion and after reperfusion. On intravital microscopy, ischaemia-reperfusion
      produced a 10-fold increase (P < 0.01) in venular attachment for MB(p).
      Attachment for MB(c) was rare. With myocardial ischaemia-reperfusion, LAD
      occlusion produced hypoperfusion and wall motion abnormalities that resolved
      after 45 min of reperfusion. At 45 min, signal enhancement in the post-ischaemic
      region was four-fold greater (P < 0.05) for MB(p) vs. MB(c). MB(p) produced low
      level enhancement in non-ischaemic myocardium in all open-chest animals,
      suggesting P-selectin expression from surgical cardiac exposure. CONCLUSION:
      Molecular imaging of P-selectin with targeted MCE can identify the presence of
      recently ischaemic myocardium in the absence of necrosis and after resolution of
      hypoperfusion and post-ischaemic stunning. This technique can potentially provide
      a method for risk stratifying patients with acute chest pain.

PMID- 17526906
TI  - Heterogeneous accumulation of uranium in the brain of rats.
AB  - Recent reports suggest that uranium can accumulate not only in known target
      organs, that is, kidneys or bones, but also in others such as central nervous
      system. In the present work, the accumulation of uranium in the brain of rats was
      studied after repeated exposure by inhalation, chronic exposure by ingestion and
      acute exposure by injection. For each route of administration, the amount of
      uranium entering the brain was low. The results showed different accumulation in
      the brain areas according to the route of intake. Injection gave a rather
      homogeneous distribution in the different brain areas, whereas both inhalation
      and ingestion yielded heterogeneous but specific accumulation. These differences
      in distribution suggest the operation of different mechanisms of delivery of
      uranium to the brain tissues.

PMID- 17526907
TI  - Development and application of anthropomorphic voxel phantom of the head for in
      vivo measurement.
AB  - The in vivo measurement of the activity deposited in the skeleton is a very
      useful source of information on human internal contaminations with transuranic
      elements, e.g. americium 241, especially for long time periods after intake.
      Measurements are performed on the skull or the larger joints such as the knee or
      elbow. The paper deals with the construction of an anthropomorphic numerical
      phantom based on CT scans, its potential for calibration and the estimation of
      the uncertainties of the detection system. The density of bones, activity
      distribution and position of the detectors were changed in individual simulations
      in order to estimate their effects on the result of the measurement. The results
      from simulations with the numerical phantom were compared with the results of
      physical phantoms.

PMID- 17526908
TI  - Diagnostic radiology in Norway trends in examination frequency and collective
      effective dose.
AB  - The objective of the present work was to determine current levels and recent
      nationwide trends in radiological examination frequency, as well as to update
      corresponding collective effective dose estimates. Examination frequencies were
      obtained from radiology management systems at all hospitals and private radiology
      enterprises across Norway in terms of number of examination codes. During the
      last decade, the overall examination frequency increased by 16% to 910 per 1000
      inhabitants, excluding nuclear imaging and dental radiology. The largest increase
      in examination frequency occurred in MRI (10-fold increase), followed by CT (more
      than doubling) and mammography (nearly 70% increase). The contribution to
      collective effective dose from radiological examinations was estimated to 4960
      man Sv or 1.09 mSv per inhabitant; representing a 40% increase from 1993 to 2002.
      CT contribution to collective effective dose was estimated to account for 59% of
      the total as opposed to 30% in the previous survey.

PMID- 17526909
TI  - CNMAN: a Chinese adult male voxel phantom constructed from color photographs of a
      visible anatomical data set.
AB  - A voxel phantom of Chinese adult male called CNMAN was constructed from color
      photographs of the first Chinese visible human data set, for radiation protection
      purpose. This data set was obtained from a 35-y-old Chinese male cadaver by a
      medical university in China. The man, 170 cm in height and 65 kg in weight, was
      dead without any pathological changes. The image size for transversal anatomical
      photographs of the whole body was 3072 x 2048. After the photographs were semi
      automatically segmented, the voxel phantom (CNMAN) with a voxel size of 0.16 mm x
      0.16 mm x 1 mm, consisting of 29 tissues or organs was constructed. Combined with
      the MCNP Monte Carlo transport code, preliminary results for radiation protection
      dosimetry were obtained based on this Chinese voxel phantom.

PMID- 17526910
TI  - Monte Carlo calculations applied to the parametrical studies in a whole body
      counter.
AB  - The use of a Monte Carlo code for the analysis and interpretation of whole body
      counting measurements is described. The sources of error are analysed and
      commented to show how a counting geometry can be improved by improving accuracy
      and precision in a measurement. The effects of body size, contamination
      distribution and counting geometry are also parameters which can be easily used
      to improve the quality of a body burden assessment. The optimisation of the
      detector (position, shielding, shape and size) is also commented on the basis of
      calculations in the photon energy range usually encountered in routine
      measurements. The results obtained from these simulations are confirmed by
      experimental results.

PMID- 17526911
TI  - Low-frequency transient electric and magnetic fields coupling to child body.
AB  - Much of the research related to residential electric and magnetic field exposure
      focuses on cancer risk for children. But until now only little knowledge about
      coupling of external transient electric and magnetic fields with the child's body
      at low frequency transients existed. In this study, current densities, in the
      frequency range from 50 Hz up to 100 kHz, induced by external electric and
      magnetic fields to child and adult human body, were investigated, as in
      residential areas, electric and magnetic fields become denser in this frequency
      band. For the calculations of induced fields and current density, the ellipsoidal
      body models are used. Current density induced by the external magnetic field (1
      microT) and external electric field (1 V/m) is estimated. The results of this
      study show that the transient electric and magnetic fields would induce higher
      current density in the child body than power frequency fields with similar field
      strength.

PMID- 17526912
TI  - Orchestration of glucose homeostasis: from a small acorn to the California oak.

PMID- 17526913
TI  - The new model NHS: performance, perceptions and expectations.
AB  - OBJECTIVE: This article analyses the transformation of the National Health
      Service (NHS) in England from a command-and-control to a mimic market model.
      AREAS OF AGREEMENT: Even while introducing market incentives and encouraging
      private providers, the new model preserves the essential characteristics of the
      NHS as a universal, tax-funded service free at the point of delivery. AREAS OF
      CONTROVERSY: The spectacle of famine among plenty -- service cutbacks at a time
      when the level of spending on the NHS is at a rate unprecedented in its history -
      raises doubts about the competence of both local managers and central policy
      makers. Payment by results gives providers an incentive to maximize activity so
      prompting questions about the future rationing of resources and the role of the
      medical profession therein. AREAS TO DEVELOP RESEARCH: The implementation and
      effects of the policies already introduced and their modification in the light of
      experience.

PMID- 17526914
TI  - The first genetic and comparative map of white lupin (Lupinus albus L.):
      identification of QTLs for anthracnose resistance and flowering time, and a locus
      for alkaloid content.
AB  - We report the first genetic linkage map of white lupin (Lupinus albus L.). An F8
      recombinant inbred line population developed from Kiev mutant x P27174 was mapped
      with 220 amplified fragment length polymorphism and 105 gene-based markers. The
      genetic map consists of 28 main linkage groups (LGs) that varied in length from
      22.7 cM to 246.5 cM and spanned a total length of 2951 cM. There were seven
      additional pairs and 15 unlinked markers, and 12.8% of markers showed segregation
      distortion at P < 0.05. Syntenic relationships between Medicago truncatula and L.
      albus were complex. Forty-five orthologous markers that mapped between M.
      truncatula and L. albus identified 17 small syntenic blocks, and each M.
      truncatula chromosome aligned to between one and six syntenic blocks in L. albus.
      Genetic mapping of three important traits: anthracnose resistance, flowering
      time, and alkaloid content allowed loci governing these traits to be defined. Two
      quantitative trait loci (QTLs) with significant effects were identified for
      anthracnose resistance on LG4 and LG17, and two QTLs were detected for flowering
      time on the top of LG1 and LG3. Alkaloid content was mapped as a Mendelian trait
      to LG11.

PMID- 17526915
TI  - A sub-proteome of Arabidopsis thaliana mature stems trapped on Concanavalin A is
      enriched in cell wall glycoside hydrolases.
AB  - N-glycosylated proteins were isolated from Arabidopsis thaliana mature stems
      using affinity chromatography on Concanavalin A Sepharose, separated by 2D
      electrophoresis and identified using nanoHPLC-MS/MS and MALDI-TOF MS. 102
      glycoproteins were identified. 94% of these proteins were predicted by
      bioinformatics to be targeted to the secretory pathway and 87% of them were
      predicted to be localized in the cell wall or at the plasma membrane. 30% of
      these proteins belong to glycoside hydrolase (GH) families with some of them
      possibly involved in the hydrolysis of cell wall polysaccharides. The second
      major class of identified proteins comprises aspartyl and serine proteases. Other
      proteins are predicted to be oxido-reductases, contain interacting domains, are
      potentially involved in signalling or have an unknown function. This is, to our
      knowledge, the first survey of plant cell wall N-glycosylated proteins.

PMID- 17526916
TI  - Arabidopsis enhanced ethylene response 4 encodes an EIN3-interacting TFIID
      transcription factor required for proper ethylene response, including ERF1
      induction.
AB  - eer4 was isolated as an Arabidopsis mutant with an extreme response to ethylene
      in dark-grown seedlings that was also found to have partial ethylene
      insensitivity at the level of ethylene-dependent gene expression, including ERF1.
      Subsequent cloning of eer4 revealed an inappropriate stop codon in a previously
      uncharacterized TFIID-interacting transcription factor homologous to human TAF12
      and yeast TAF61. Genetic and pharmacological analysis demonstrated that the eer4
      phenotype is strictly ethylene dependent in seedlings, yet a double mutant with
      the partially ethylene-insensitive Arabidopsis mutant, ein3-1, had restored
      ethylene responsiveness, indicating that eer4 also regulates a previously unknown
      resetting or dampening mechanism for the ethylene signalling pathway. Consistent
      with the absolute requirement of EER4 for ERF1 expression, biochemical analysis
      showed that EER4 is localized to the nucleus where it probably recruits EIN3 and
      probably other transcription factors along with components of the TFIID complex
      for expression of a subset of genes required for either manifestation or
      subsequent dampening of the response to ethylene.

PMID- 17526917
TI  - Caspofungin for the treatment of less common forms of invasive candidiasis.
AB  - OBJECTIVES: Caspofungin has demonstrated efficacy in invasive candidiasis.
      However, in a comparative study, most patients (>83%) had candidaemia. Therefore,
      we performed a study in patients with non-fungaemic invasive candidiasis.
      PATIENTS AND METHODS: Adults with proven non-fungaemic invasive candidiasis or
      probable chronic disseminated candidiasis (CDC) received caspofungin primary or
      salvage monotherapy. Most patients received 50 mg daily following a 70 mg loading
      dose. Patients with endocarditis, osteomyelitis or septic arthritis received
      caspofungin at 100 mg daily and were allowed dose escalation up to 150 mg.
      Primary efficacy endpoint was the overall response at end of caspofungin therapy.
      A favourable overall response required complete resolution of symptoms and either
      eradication of Candida or radiographic resolution. RESULTS: All 48 patients
      enrolled had confirmed infection and received>or=1 dose of caspofungin. At study
      entry, 8% were neutropenic. The mean APACHE II score was 14.3. Most infections
      were due to Candida albicans (60%) or Candida glabrata (14%). The overall success
      at end of caspofungin therapy was 81%. Success by site of infection was as
      follows: peritonitis 77% (10/13), abdominal abscess 89% (8/9), CDC 88% (7/8),
      osteomyelitis/septic arthritis 100% (4/4), endocarditis 33% (1/3) and multiple
      sites 75% (6/8). Outcomes were similar across Candida spp. None of the patients
      had a serious drug-related adverse event or discontinued caspofungin due to
      toxicity. Overall mortality until 12 week follow-up was 23%. CONCLUSIONS: In deep
      seated invasive candidiasis, including peritonitis, abdominal abscesses, CDC and
      arthritis, caspofungin was effective and safe at regular doses and up to 100 mg
      daily.

PMID- 17526918
TI  - Hardy weinberg expectations in canine breeds: implications for genetic studies.
AB  - Hardy-Weinberg equilibrium (HWE) is a useful indicator of genotype frequencies
      within a population and whether they are based on a valid definition of alleles
      and a randomly mating sample. HWE assumes a stable population of adequate size
      without selective pressures and is used in human genetic studies as a guide to
      data quality by comparing observed genotype frequencies to those expected within
      a population. The calculation of genetic associations in case-control studies
      assume that the population is "in HWE." Canine breed populations deviate away
      from many of the criteria for HWE, and if genetic markers are not in HWE,
      conventional statistical analysis cannot be performed. To date, little attention
      has been paid as to whether genetic markers in dog breeds are distributed in
      compliance to HWE. In this study, 109 single-nucleotide polymorphisms (SNPs) were
      genotyped from 13 genes in a cohort of 894 dogs encompassing 33 breeds. Analysis
      of the entire cohort of dogs revealed a significant deviation away from HWE for
      all SNPs tested (P < 0.00001); analysis of the cohort stratified by breed and
      subbreed indicated that the majority of the markers complied with HWE
      expectation. This suggests that canine case-control association studies will be
      valid if performed within defined breeds.

PMID- 17526919
TI  - Isolation and functional analysis of a MYB transcription factor gene that is a
      key regulator for the development of red coloration in apple skin.
AB  - Red coloration of apple (Malus x domestica) skin is an important determinant of
      consumer preference and marketability. Anthocyanins are responsible for this
      coloration, and their accumulation is positively correlated with the expression
      level of anthocyanin biosynthetic genes. Regulation of expression of these genes
      is believed to be controlled by MYB transcription factors, and the MYB
      transcription factors involved in the activation of anthocyanin biosynthetic
      genes have been isolated in various plants. In the present study, we isolated and
      characterized a MYB transcription factor gene (MdMYBA) from apple skin.
      Characterization of MdMYBA demonstrated that (i) MdMYBA expression was
      specifically regulated depending on the tissue and cultivar/species; (ii) its
      expression level was much higher in a deep-red cultivar ('Jonathan') than in a
      pale-red cultivar ('Tsugaru'); (iii) when cauliflower mosaic virus 35S::MdMYBA
      was introduced into the cotyledons of apple seedlings by means of a transient
      assay, reddish-purple spots were induced, and MdMYBA also induced anthocyanin
      accumulation in reproductive tissues of transgenic tobacco; (iv) the expression
      of MdMYBA was induced by UV-B irradiation and low-temperature treatment, both of
      which are known to be important in the promotion of anthocyanin accumulation in
      apple skin; (v) MdMYBA bound specifically to an anthocyanidin synthase (MdANS)
      promoter region in a gel-shift assay; and (vi) MdMYBA was mapped to the near
      region of the BC226-STS (a1) marker for the red skin color locus (R(f)). These
      results suggest that MdMYBA is a key regulatory gene in anthocyanin biosynthesis
      in apple skin.

PMID- 17526921
TI  - Bisphosphonates in the renal patient.

PMID- 17526923
TI  - Faculty of Public Health leadership interview by Aruna Stannard.

PMID- 17526924
TI  - SNPs in the FOXP3 gene region show no association with Juvenile Idiopathic
      Arthritis in a UK Caucasian population.
AB  - OBJECTIVE: A region on the short arm of the X-chromosome, Xp11, has previously
      been linked to childhood-onset polyarthritis. Mapping to the linked region is
      FOXP3, a transcription factor that regulates regulatory T cell (T(reg))
      development and function. The objective of this study was to determine whether
      single nucleotide polymorphisms (SNPs) in the FOXP3 gene region contribute to JIA
      susceptibility. METHOD: Nine FOXP3 SNPs were genotyped in 761 JIA cases and 402
      controls using the Sequenom MassARRAY system. Association was measured using
      either chi(2) or Fisher's exact test at the allelic and genotypic level.
      Furthermore, cases and controls were stratified by gender and association
      measured for each stratum. RESULTS: None of the SNPs showed an association with
      JIA. Similarly, the lack of association was also evident in both the female and
      male cohorts. CONCLUSION: Although FOXP3 presents itself as a good candidate for
      contributing to JIA susceptibility, this study, which was powered to detect
      associations with genotypic relative risk >2 in the female cohort, has failed to
      find an association between SNPs in the FOXP3 gene region and JIA.

PMID- 17526926
TI  - Ultrasonography is a sensitive tool for monitoring localized scleroderma.
AB  - OBJECTIVE: To examine the usefulness of ultrasonography (USG) for monitoring
      paediatric localized scleroderma (LS). METHODS: A retrospective chart review of
      six paediatric patients who had USG of their LS. RESULTS: USG detected several
      abnormalities in active lesions including increased blood flow, increased
      echogenicity and loss of subcutaneous fat. USG findings corresponded with
      clinical assessment, and documented regeneration of subcutaneous fat and
      reduction in lesion size during treatment. In one patient, USG was more sensitive
      than magnetic resonance evaluation. CONCLUSION: USG was found to be a sensitive
      tool for assessing the activity and extent of LS lesions in paediatric patients.
      Further studies are needed to assess its general applicability for monitoring
      these patients.

PMID- 17526927
TI  - Decreased bone strength in HLA-B27 transgenic rat model of spondyloarthropathy.
AB  - OBJECTIVE: To investigate the nature of osteopenia/osteoporosis in
      spondyloarthropathy, an inflammatory disorder, using the HLA-B27 transgenic rat
      model. METHODS: HLA-B27 transgenic rats were housed individually and sacrificed
      at the peak of their disease (8-month-old). The spine and femurs were removed and
      stored in saline at -20 degrees C until analysis. The bone structure and strength
      were determined using a micro-computed tomography (micro-CT) device (Scanco
      Medical) and mechanical testing (Instron 5543). Vertebral bodies and femurs were
      scanned to determine trabecular structural properties in terms of bone volume
      (BV/TV), trabecular thickness, and spacing. After scanning, the mid-shaft femurs
      were subjected to a 3-point bending test (along anterior-posterior direction),
      the femoral necks were tested in bending, and the vertebral bodies (L4) were
      tested in compression. Structural (ultimate/yield load, stiffness) and apparent
      material (ultimate/yield stress, modulus) strength parameters were then
      determined. RESULTS: The majority of the bone structural and strength parameters
      were significantly lower (P < 0.05) in the HLA-B27 transgenic rats as compared
      with control littermates. Micro-CT data suggested that the transgenic animals had
      lower BV/TV and trabecular thickness in their vertebral bodies. The poor
      trabecular structure observed in HLA-B27 rats is also indicative of the poor
      biomechanical strength properties in the vertebral bodies as well. CONCLUSION:
      The HLA-B27 transgenic rats develop bone fragility similar to that seen in
      spondyloarthropathy and may be an important model for the study of osteoporosis
      in spondyloarthropathy.

PMID- 17526928
TI  - Sacroiliac joint biopsies in early sacroiliitis.

PMID- 17526929
TI  - Angiotensin II protects fibroblast-like synoviocytes from apoptosis via the AT1
      NF-kappaB pathway.
AB  - OBJECTIVE: To evaluate the effects of angiotensin II (Ang II) treatment on
      apoptosis of fibroblast-like synoviocytes (FLS) from patients with osteoarthritis
      (OA) and rheumatoid arthritis (RA). METHODS: AT1 receptor expression was detected
      by western blotting and flow cytometry. Apoptosis induction was quantified by
      nucleosome ELISA and by TUNEL; cell proliferation was determined by a
      bromodeoxyuridine (BrdU) incorporation assay. Silencing of p65 NF-kappaB was
      obtained by using a specific siRNA. Caspase 3 activation was evaluated by a
      colorimetric assay and its cleavage by western blotting. RESULTS: AT1 expression
      resulted comparable in FLS from OA and RA patients. Ang II pre-treatment reduced
      FLS apoptotic response to serum starvation and nitric oxide (NO) exposure. This
      protective effect was reverted in the presence of the AT1 receptor antagonist
      losartan as well as after silencing the expression of NF-kappaB. Moreover, FLS
      treatment with the caspase inhibitor z-VAD-fmk cancelled this Ang II effect on
      apoptosis. Caspase 3 activation was reduced in presence of Ang II. CONCLUSIONS:
      Ang II could represent an important mediator involved in FLS expansion, reducing
      their capacity to undergo apoptosis, through the activation of NF-kappaB and the
      blockage of caspase cascade.

PMID- 17526930
TI  - Disease pattern of spondyloarthropathies in Spain: description of the first
      national registry (REGISPONSER) extended report.
AB  - OBJECTIVE: The national registry of spondyloarthropathies (REGISPONSER) is
      launched to classify patients with this group of diseases treated in Spanish
      rheumatology clinics. This manuscript describes the methodological and
      organizational background as well as characteristics of patients finally
      included, and provides a comparative analysis between characteristics of both
      ankylosing spondylitis and undifferentiated spondyloarthropathy groups of
      patients. PATIENTS AND METHODS: Twelve members of the GRESSER group have
      participated in the registry, for a one-year recruitment period. All
      consecutively registered adult patients treated in their clinics met the
      classification criteria of the European Spondyloarthropathies Study Group (ESSG).
      Data collected reflect the socio-demographic characteristics, as well as disease
      activity and functional status, clinical form at onset, treatment used and
      quality of life; all measured by standard instruments. RESULTS: Throughout 1 yr,
      1385 patients have been included in the registry: 939 males (68%) and 440 females
      (32%), with an average age of 47 +/- 13 years (mean +/- s.d.), and an average
      disease duration of 12 +/- 9 years. Diagnoses of the included patients were: AS
      (n = 842, 61%), PsA (n = 290, 21%), u-SpA (n = 205, 15%), reactive arthritis (n =
      16, 1.2%), inflammatory bowel disease arthritis (n = 13, 0.9%) and JCA
      spondyloathropathy (n = 13, 0.9%). Regarding clinical form, 54% had axial
      disease, 20% peripheral disease, 24% mixed disease and 0.6% isolated enthesitic
      form. Low-back pain was the first symptom reported in 53% of the patients, and
      most common extra-articular disease manifestations were psoriasis (25%), anterior
      uveitis (16%) and intestinal inflammatory disease (4%). Some kind of work
      disability was reported by 353 patients (25.5%). CONCLUSIONS: Such databases are
      very useful to obtain information about characteristics of SpA patients treated
      in a certain location or following a specific treatment practice, and provide a
      tool for assessing the impact of the disease. Data collected in this registry
      provide an appropriate clinical and demographic profile of patients suffering
      from SpA in Spain.

PMID- 17526931
TI  - Suppression of diacylglycerol acyltransferase-2 (DGAT2), but not DGAT1, with
      antisense oligonucleotides reverses diet-induced hepatic steatosis and insulin
      resistance.
AB  - Nonalcoholic fatty liver disease (NAFLD) is a major contributing factor to
      hepatic insulin resistance in type 2 diabetes. Diacylglycerol acyltransferase
      (Dgat), of which there are two isoforms (Dgat1 and Dgat2), catalyzes the final
      step in triglyceride synthesis. We evaluated the metabolic impact of
      pharmacological reduction of DGAT1 and -2 expression in liver and fat using
      antisense oligonucleotides (ASOs) in rats with diet-induced NAFLD. Dgat1 and
      Dgat2 ASO treatment selectively reduced DGAT1 and DGAT2 mRNA levels in liver and
      fat, but only Dgat2 ASO treatment significantly reduced hepatic lipids
      (diacylglycerol and triglyceride but not long chain acyl CoAs) and improved
      hepatic insulin sensitivity. Because Dgat catalyzes triglyceride synthesis from
      diacylglycerol, and because we have hypothesized that diacylglycerol accumulation
      triggers fat-induced hepatic insulin resistance through protein kinase C epsilon
      activation, we next sought to understand the paradoxical reduction in
      diacylglycerol in Dgat2 ASO-treated rats. Within 3 days of starting Dgat2 ASO
      therapy in high fat-fed rats, plasma fatty acids increased, whereas hepatic
      lysophosphatidic acid and diacylglycerol levels were similar to those of control
      rats. These changes were associated with reduced expression of lipogenic genes
      (SREBP1c, ACC1, SCD1, and mtGPAT) and increased expression of
      oxidative/thermogenic genes (CPT1 and UCP2). Taken together, these data suggest
      that knocking down Dgat2 protects against fat-induced hepatic insulin resistance
      by paradoxically lowering hepatic diacylglycerol content and protein kinase C
      epsilon activation through decreased SREBP1c-mediated lipogenesis and increased
      hepatic fatty acid oxidation.

PMID- 17526932
TI  - Sterol regulatory element-binding protein-2- and liver X receptor-driven dual
      promoter regulation of hepatic ABC transporter A1 gene expression: mechanism
      underlying the unique response to cellular cholesterol status.
AB  - ABC transporter A1 (ABCA1) mediates and rate-limits biogenesis of high density
      lipoprotein (HDL), and hepatic ABCA1 plays a major role in regulating plasma HDL
      levels. HDL generation is also responsible for release of cellular cholesterol.
      In peripheral cells ABCA1 is up-regulated by the liver X receptor (LXR) system
      when cell cholesterol increases. However, cholesterol feeding has failed to show
      a significant increase in hepatic ABCA1 gene expression, and its expression is up
      regulated by statins (3-hydroy-3-methylglutaryl-CoA reductase inhibitors),
      suggesting distinct regulation. In this study we investigated the mechanism of
      regulation of the rat hepatic ABCA1 gene and identified two major ABCA1
      transcripts and two corresponding promoter regions. Compactin activated the novel
      liver-type promoter in rat hepatoma McARH7777 cells by binding the sterol
      regulatory element-binding protein-2 (SREBP-2). In contrast, compactin repressed
      the previously identified peripheral-type promoter in an LXR-responsive element
      dependent but not E-box-dependent manner. Thus, compactin increased the liver
      type transcript and decreased the peripheral-type transcript. The same two
      transcripts were also dominant in human and mouse livers, whereas the intestine
      contains only the peripheral-type transcript. Treatment of rats with pravastatin
      and a bile acid binding resin (colestimide), which is known to activate SREBP-2
      in the liver, caused a reduction in the hepatic cholesterol level and the same
      differential responses in vivo, leading to increases in hepatic ABCA1 mRNA and
      protein and plasma HDL levels. We conclude that the dual promoter system driven
      by SREBP-2 and LXR regulates hepatic ABCA1 expression and may mediate the unique
      response of hepatic ABCA1 gene expression to cellular cholesterol status.

PMID- 17526933
TI  - Polyunsaturated fat in the methionine-choline-deficient diet influences hepatic
      inflammation but not hepatocellular injury.
AB  - Methionine-choline-deficient (MCD) diets that cause steatohepatitis in rodents
      are typically enriched in polyunsaturated fat. To determine whether the fat
      composition of the MCD formula influences the development of liver disease, we
      manufactured custom MCD formulas with fats ranging in PUFA content from 2% to 59%
      and tested them for their ability to induce steatohepatitis. All modified-fat MCD
      formulas caused identical degrees of hepatic steatosis and resulted in a similar
      distribution of fat within individual hepatic lipid compartments. The fatty acid
      composition of hepatic lipids, however, reflected the fat composition of the
      diet. Mice fed a PUFA-rich MCD formula showed extensive hepatic lipid
      peroxidation, induction of proinflammatory genes, and histologic inflammation.
      When PUFAs were substituted with more saturated fats, lipid peroxidation,
      proinflammatory gene induction, and hepatic inflammation all declined
      significantly. Despite the close relationship between PUFAs and hepatic
      inflammation in mice fed MCD formulas, dietary fat had no impact on MCD-mediated
      damage to hepatocytes. Indeed, histologic apoptosis and serum alanine
      aminotransferase levels were comparable in all MCD-fed mice regardless of dietary
      fat content. Together, these results indicate that dietary PUFAs promote hepatic
      inflammation but not hepatotoxicity in the MCD model of liver disease. These
      findings emphasize that individual dietary nutrients can make specific
      contributions to steatohepatitis.

PMID- 17526934
TI  - Effects of different doses of atorvastatin on human apolipoprotein B-100, B-48,
      and A-I metabolism.
AB  - Nine hypercholesterolemic and hypertriglyceridemic subjects were enrolled in a
      randomized, placebo-controlled, double-blind, crossover study to test the effect
      of atorvastatin 20 mg/day and 80 mg/day on the kinetics of apolipoprotein B-100
      (apoB-100) in triglyceride-rich lipoprotein (TRL), intermediate density
      lipoprotein (IDL), and LDL, of apoB-48 in TRL, and of apoA-I in HDL. Compared
      with placebo, atorvastatin 20 mg/day was associated with significant reductions
      in TRL, IDL, and LDL apoB-100 pool size as a result of significant increases in
      fractional catabolic rate (FCR) without changes in production rate (PR). Compared
      with the 20 mg/day dose, atorvastatin 80 mg/day caused a further significant
      reduction in the LDL apoB-100 pool size as a result of a further increase in FCR.
      ApoB-48 pool size was reduced significantly by both atorvastatin doses, and this
      reduction was associated with nonsignificant increases in FCR. The lathosterol
      campesterol ratio was decreased by atorvastatin treatment, and changes in this
      ratio were inversely correlated with changes in TRL apoB-100 and apoB-48 PR. No
      significant effect on apoA-I kinetics was observed at either dose of
      atorvastatin. Our data indicate that atorvastatin reduces apoB-100- and apoB-48
      containing lipoproteins by increasing their catabolism and has a dose-dependent
      effect on LDL apoB-100 kinetics. Atorvastatin-mediated changes in cholesterol
      homeostasis may contribute to apoB PR regulation.

PMID- 17526935
TI  - Treatment with phytoestrogen alpha-zearalanol might protect neurons of
      hippocampus in ovariectomized rats.
AB  - Although neuroprotective effects of estrogen on postmenopausal women have been
      recognized, an associated increased incidence of uterine and breast tumors has
      jeopardized the clinical use of estrogen. This study was designed to evaluate the
      neuroprotective effects of a novel phytoestrogen alpha-zearalanol (alpha-ZAL), on
      ovariectomized (OVX) rats. Adult Wistar rats were ovariectomized or sham-operated
      and treatment with equivalent doses of 17beta-estradiol or alpha-ZAL for 5 wk.
      Uteruses have been weighted and stained by hematoxylin and eosin for morphology
      analysis. The expression of synaptophysin and parvalbumin in hippocampus were
      evaluated by immunohistochemistry assays. Our experiments indicated that the
      synaptophysin and parvalbumin-positive areas were significantly decreased in the
      OVX group compared to the sham group, alpha-ZAL or 17beta-estradiol
      administration can reverse the effects. Although alpha-ZAL and 17beta-estradiol
      treatments reconciled uterus weight loss which was induced by ovariectomy, the
      effect of alpha-ZAL was less than 17beta-estradiol. This result suggests that
      alpha-ZAL may effectively abate neurons loss in the hippocampus while slightly
      promoting weight gain of the uterus.

PMID- 17526936
TI  - High prevalence of PROP1 gene mutations in Hungarian patients with childhood
      onset combined anterior pituitary hormone deficiency.
AB  - Combined pituitary hormone deficiency is characterized by the impaired production
      of pituitary hormones, commonly including growth hormone. The pathomechanism of
      the childhood-onset form of this disorder may involve germline mutations of genes
      encoding pituitary transcription factors, of which PROP1 gene mutations have been
      studied most extensively. However, controversy exists about the significance of
      PROP1 gene mutations, as both low and high frequencies have been reported in
      these patients. Because the different results may be related to differences in
      patient populations and/or the variability of clinical phenotypes, we performed
      the present study to examine the prevalence and spectrum of PROP1 gene mutations
      in 35 patients with non-acquired childhood-onset growth hormone deficiency
      combined with at least one other anterior pituitary hormone deficiency. Genetic
      testing indicated the presence of disease-causing mutations in exons 2 and 3 of
      the PROP1 gene in 15 patients (43% of all patients; homozygous mutations in 10
      patients and compound heterozygous mutations in 5 patients). Comparison of
      clinical data of patients with and without PROP1 gene mutations failed to show
      significant differences, except an earlier growth retardation detected in
      patients with PROP1 gene mutations. In one patient with PROP1 gene mutation,
      radiologic imaging showed an enlargement of the anterior lobe of the pituitary,
      whereas the other patients had hypoplastic or normal pituitary gland. All
      patients with PROP1 gene mutations had normal posterior pituitary lobe by
      radiologic imaging. These results indicate that using our inclusion criteria for
      genetic testing, PROP1 gene mutations can be detected in a high proportion of
      Hungarian patients with non-acquired childhood-onset growth hormone deficiency
      combined with at least one other anterior pituitary hormone defect.

PMID- 17526937
TI  - Tamoxifen activates CYP3A4 and MDR1 genes through steroid and xenobiotic receptor
      in breast cancer cells.
AB  - Cytochrome P450 monooxygenase 3A4 (CYP3A4) and P-glycoprotein, encoded by
      multidrug resistance 1 (MDR1) gene, are responsible for the metabolism of
      endogenous steroids, prescribed drugs, and xenobiotics. Both genes are regulated
      by steroid and xenobiotic receptor (SXR), a member of nuclear hormone receptors.
      Various endogenous steroids and drugs function as ligands of SXR. Although
      CYP3A4, MDR1, and SXR are expressed mainly in the liver and the small intestine,
      these gene products are also expressed in breast cancer cells. Because tamoxifen
      (TAM) is known to be metabolized by CYP3A4 and P-glycoprotein, we investigated
      the effect of TAM on these SXR-targeted genes in breast cancer cells. Transient
      transfection-based reporter gene assays showed 4-hydroxy TAM activated the SXR
      mediated transcription through CYP3A4 and MDR1 promoters in a ligand- and
      receptor concentration-dependent manner. We confirmed the binding of 4-hydroxy
      TAM to SXR by ligand binding assay. Moreover, semiquantitative RT-PCR studies
      revealed that 4-hydroxy TAM activated the expression of CYP3A4 and MDR1 mRNA in
      MCF-7 cells. These results suggest that TAM induces CYP3A4 and MDR1 gene
      expression through SXR, which may affect TAM metabolic pathway in breast cancer
      cells.

PMID- 17526938
TI  - Effect of ethanol on 24-h hormonal changes in prolactin release mechanisms in
      growing male rats.
AB  - This study analyzes the effect of chronic ethanol feeding on 24-h variation of
      hypothalamic-pituitary mechanisms involved in prolactin regulation in growing
      male Wistar rats. Animals were maintained under a 12:12 h light/dark photoperiod
      (lights off at 2000 h), and they received a liquid diet for 4 wk, starting on d
      35 of life. The ethanol-fed group received a similar diet to controls except that
      maltose was isocalorically replaced by ethanol. Ethanol replacement provided 36%
      of the total caloric content of the diet. Rats were killed at six time intervals
      every 4 h, beginning at 0900 h. Mean concentration of serum prolactin in ethanol
      fed rats was 58.7% higher than in controls. Peak circulating prolactin levels
      occurred at the early phase of the activity span in both groups of rats, whereas
      a second peak was found late in the resting phase in ethanol-fed rats only. In
      control rats, median eminence dopamine (DA), serotonin (5-HT), gamma-aminobutyric
      acid (GABA), and taurine levels exhibited two maxima, the major one preceding
      prolactin release and a second one during the first part of the resting phase.
      Median eminence DA and 5-HT turnover (as measured by 3,4-dihydroxyphenylacetic
      acid, DOPAC/DA, and 5-hydroxyindoleacetic acid, 5-HIAA/5-HT ratio) showed a
      single maximum preceding prolactin, at 0100 h. Ethanol treatment did not affect
      median eminence DA or 5-HT levels but it decreased significantly their turnover
      rate. The midday peak in DA and 5-HT levels (at 1300 h) was abolished and the
      night peak (at 0100 h) became spread and blunted in the ethanol-fed rats. This
      was accompanied with the disappearance of the 0100 h peak in DA and 5-HT turnover
      and the occurrence of a peak in 5-HT turnover at 1700 h. Ethanol intake
      suppressed the night peak in median eminence GABA and taurine (at 0100 h) as well
      as the midday peak of GABA. Ethanol augmented pituitary levels of DOPAC and 5
      HIAA. The results indicate that chronic ethanol administration affects the
      mechanisms that modulate the circadian variation of prolactin release in growing
      male rats.

PMID- 17526939
TI  - Observation of hypertension in children with 21-hydroxylase deficiency: a
      preliminary report.
AB  - The most common cause of congenital adrenal hyperplasia is 21-hydroxylase
      deficiency (21OHD). The prevalence of hypertension (HTN) in children with 21OHD
      is unknown, and HTN has not been reported to be a component of this disorder. As
      children with 21OHD are at risk of developing obesity, we hypothesized that an
      elevated body mass index (BMI) would be a predictive factor in the development of
      HTN. A retrospective chart review of children with 21OHD seen in our pediatric
      endocrine clinics for the past 21 yr was performed. Ninety-one children with
      21OHD were identified (54% female). Of these children, six (6.6%) had HTN, and
      five (5.6%) had essential HTN, which was defined as HTN of unknown etiology.
      Elevated body mass index was not a determining factor in the development of HTN.
      Children with 21OHD do appear to have a higher prevalence of HTN when compared to
      historical reports of pediatric populations. The coexistence of HTN with a salt
      wasting state and mineralocorticoid deficiency in some children with 21OHD is
      paradoxical and of unclear etiology.

PMID- 17526940
TI  - Elevated serum RBP4 is associated with insulin resistance in women with
      polycystic ovary syndrome.
AB  - Retinol binding protein 4 (RBP4) is a novel adipocyte-secreted protein that
      contributes to systemic insulin resistance. Experiments in mice suggest that
      elevated RBP4 causes insulin resistance. In the present study, we determined
      serum RBP4 concentration and evaluated its association with insulin resistance in
      women with polycystic ovarian syndrome (PCOS); 39 PCOS women and 45 healthy
      control subjects were enrolled in this study. Serum RBP4, fasting plasma glucose
      (FPG) and fasting serum insulin (FINS) were measured in all subjects.
      Furthermore, oral glucose tolerance test (OGTT), Botnia clamp (an intravenous
      glucose tolerance test followed by an euglycemic hyperinsulinemic clamp), and
      measurements of sex hormones were performed in 13 control subjects and all the
      PCOS women. The levels of serum RBP4 were elevated in PCOS women compared with
      the control (11.69 +/- 6.72 versus 7.75 +/- 5.96 microg/mL, p = 0.006). RBP4
      levels were positively correlated with WHR (r = 0.216, p = 0.048), and
      intravenous glucose tolerance test beta cell index (IVGTT-beta index) which
      reflected beta cell function (r = 0.309, p = 0.028), but were inversely
      correlated with M value during Botnia clamp, which represented insulin
      sensitivity (r = -0.362, p = 0.008). No correlation was found between RBP4 and
      age, BMI, blood pressure, FPG, FINS, 2-h postprandial glucose, 2-h postprandial
      insulin, free testosterone, total testosterone, follicle-stimulating hormone
      (FSH), or luteinizing hormone (LH). In a linear stepwise regression analysis with
      a model including age, BMI, WHR, free testosterone, IVGTT-beta index, and M value
      as independent variables, only M value showed significant correlation with serum
      RBP4 levels (r2 = 0.105, f = 6.640, p = 0.012). In conclusion, serum RBP4 levels
      are significantly increased in PCOS women and associated with insulin resistance,
      which indicates that RBP4 may be a contributing factor linking adipose tissue
      with insulin resistance in PCOS.

PMID- 17526941
TI  - Early response to venlafaxine antidepressant correlates with lower ACTH levels
      prior to pharmacological treatment.
AB  - A link between stressful life events and development or exacerbation of
      depression has been established via a large body of evidence. An alteration in
      the regulation of the hypothalamic-pituitary-adrenal (HPA) axis in depression has
      also been associated with an increase in cortisol secretion. As arginine
      vasopressin (AVP) plays an important role in the activation of HPA axis during
      stress, the present study investigated ACTH and cortisol secretory response
      induced by an AVP-related peptide desmopressin (ddAVP) in patients with major
      depression. Prior to antidepressant treatment, endocrinological parameters were
      evaluated and correlated with the clinical response to venlafaxine treatment,
      which offers a dual antidepressant action. Depressive patients with no other
      psychiatric pathology were evaluated with 17-item Hamilton Depression Scale (HAM
      D) in order to follow-up the response to venlafaxine. After 1 wk of treatment,
      60% of patients reduced their initial HAM-D score to at least 25%; this group was
      classified as early responders. The other group (40%) started to reduce
      significantly their HAM-D score after 3 wk of treatment and was classified as
      late responders. After 6 wk of treatment both groups have reduced HAM-D score to
      at least 25% of the baseline score. Prior to the pharmacological treatment, both
      early and late responders showed salivary cortisol rhythm and urinary free
      cortisol (UFC) in 24-h similar to healthy subjects. However, we did observe
      differences in basal ACTH secretion, showing that the late responder group had
      higher basal ACTH than both early responders and controls. The ddAVP challenge
      promoted a robust secretion of ACTH only in late responders, suggesting a
      different sensitivity of pituitary vasopressin receptor. The differences in
      clinical response to venlafaxine among depressive patients seem to be related to
      endocrinological parameters.

PMID- 17526942
TI  - Association of DNA methylation and epigenetic inactivation of RASSF1A and beta
      catenin with metastasis in small bowel carcinoid tumors.
AB  - We analyzed promoter methylation of RASSF1A, CTNNB1, CDH1, LAMB3, LAMC2, RUNX3,
      NORE1A, and CAV1 using methylation-specific PCR in 33 cases of small bowel
      carcinoid with both matched primary and metastatic tumors. The methylation status
      of RASSF1A and CTNNB1 were also determined in six primary appendiceal carcinoid
      tumors. Two neuroendocrine cell lines, NCI-H727 and HTB-119, were analyzed for
      promoter methylation. Immunohistochemical analyses for RASSF1A and beta-catenin
      were performed in 28 matched primary and metastatic tumors. Western blot analysis
      for RASSF1A and beta-catenin was also performed. Normal enterochromaffin cells
      were unmethylated in all eight genes examined. RASSF1A and CTNNB1 were
      unmethylated in appendiceal carcinoids. Methylation of RASSF1A and CTNNB1
      promoters was more frequent in metastatic compared to primary tumors (p = 0.013
      and 0.004, respectively). The NCI-H727 and HTB-119 cells lines were methylated in
      the RASSF1A promoter region, and after treatment with 5-aza-2'-deoxycytidine (5
      AZA), RASSF1A mRNA was expressed in both cell lines. Western blot results for
      RASSF1A and beta-catenin supported the methylation-specific PCR findings. The
      other six genes did not show significant differences. These results suggest that
      increased methylation of RASSF1A and CTNNB1 may play important roles in
      progression and metastasis of small bowel carcinoid tumors.

PMID- 17526943
TI  - LOH on chromosome 11q, but not SDHD and Men1 mutations was frequently detectable
      in Chinese patients with pheochromocytoma and paraganglioma.
AB  - Recently, the succinate dehydrogenase subunit D (SDHD) gene has been reported as
      one of the major susceptibility genes for pheochromocytoma (PCC) and
      paraganglioma (PGL). In addition, loss of heterozygosity (LOH) on chromosome 11,
      mainly in 11q23 and 11q13, is observed frequently in PGL. Based on the fact that
      mutation frequency of the SDHD gene is less than that of allelic loss at
      chromosome11q, where the SDHD gene is located, this region may contain other
      candidate tumor-suppressor genes involved in pathogenesis of PCC/PGL. The tumor
      suppressor gene Men1 located in 11q13 is responsible for multiple endocrine
      neoplasia type 1 (Men1). However, the involvement of the Men1 gene in
      tumorigenesis of sporadic PCC/PGL is yet to be determined. To understand the
      roles of the two tumor-suppressor genes and LOH on chromosome 11q in Chinese
      patients with sporadic PCC or PGL, we performed mutation detection of the SDHD
      and Men1 genes in tumors from 35 Chinese patients with PCC/PGL; we also did LOH
      analysis at chromosome 11q for 25 patients out of the 35. No mutation was found
      in all of 35 patients. However, LOH was detected at one or more loci in 11 of the
      25 (44%) tumor samples. The highest frequency of LOH occurred at D11S2006 (41%).
      Our results suggested that mutation in SDHD or Men1 gene was not found in Chinese
      patients with sporadic PCC/PGL. However the loss of chromosome 11q might be
      critical in development of PCC or PGL.

PMID- 17526944
TI  - In vivo inhibition of steroidogenic acute regulatory protein expression by
      dexamethasone parallels induction of the negative transcription factor DAX-1.
AB  - In this study, we investigated the effect of dexamethasone on the synthesis of
      steroidogenic acute regulatory protein (StAR) and the expression of DAX-1 (dosage
      sensitive sex reversal adrenal hypoplasia congenita critical region on the X
      chromosome, gene 1) and SF-1 (steroidogenic factor-1) in vivo. Male rats were
      treated with dexamethasone (0.4 and 4 mg/kg body wt per day) by intraperitoneal
      injections using phosphate-buffered saline as the vehicle for 7 d. At the end of
      7 d, serum testosterone levels were decreased. Response to luteinizing hormone
      (LH) and 8-bromo-cyclic-AMP (8-Br-cAMP) in vitro was reduced in testicular cells
      isolated from dexamethasone-treated rat testes. Dexamethasone decreased LH
      stimulated cAMP production. The conversion of 22(R)-hydroxycholesterol,
      pregnenolone, 17-hydroxypregnenolone, dehydroepiandrosterone, and androstenedione
      to testosterone was not affected by dexamethasone. Dexamethasone increased DAX-1
      expression and concordantly decreased StAR protein and mRNA in testicular cells.
      The increase in DAX-1 protein corresponded to a 57% reduction in StAR mRNA levels
      concomitant with a 79% reduction in serum testosterone levels. Dexamethasone had
      no effect on the level of SF-1, but increased the amount of complexed DAX-1-SF-1.
      Dexamethasone in vitro suppressed StAR promoter activity when an increasing
      amount of DAX-1 cDNA was transfected. These results demonstrate that
      dexamethasone increases expression of DAX-1, which results in increased amounts
      of complexed DAX-1-SF-1, in the absence of any change in the expression of SF-1.
      These observations strongly support the concept that dexamethasone suppresses rat
      testicular testosterone production, at least in part, by increasing the amount of
      complexed DAX-1-SF-1 in these cells, which leads directly to decreased
      availability of free SF-1 and, therefore, decreased activation of transcription
      of the rat StAR gene.

PMID- 17526945
TI  - Four cardiac hormones eliminate up to 82% of human medullary thyroid carcinoma
      cells within 24 hours.
AB  - Four cardiac hormones, i.e., atrial natriuretic peptide, vessel dilator, long
      acting natriuretic peptide, and kaliuretic peptide, which have anticancer
      effects, were evaluated for the first time on any endocrine cancer to determine
      if they have anticancer effects in an endocrine cancer. These four cardiac
      hormones were evaluated for their anticancer, DNA synthesis, and receptor status
      in human medullary thyroid cancer cells. There was a significant (p < 0.001)
      decrease in human medullary thyroid cancer cells with each 10-fold increase from
      1 to 100 microM of the four cardiac hormones. There was an 81%, 68%, 71%, and 66%
      elimination within 24 h of medullary thyroid cancer cells secondary to vessel
      dilator, kaliuretic peptide, atrial natriuretic peptide, and long-acting
      natriuretic peptide, respectively (p < 0.0001). Three days after treatment with
      these peptide hormones, there was no proliferation of the medullary thyroid
      cancer cells. These cardiac hormones decreased DNA synthesis in the medullary
      thyroid cells from 65% to 84% (p < 0.0001). Western blots revealed natriuretic
      peptide receptors-A and -C were present in human medullary thyroid cancer cells.
      These results indicate the four cardiac hormones have potent anticancer effects
      by eliminating up to 82% of human medullary thyroid carcinoma cells within 24 h
      of treatment.

PMID- 17526946
TI  - Effects of estradiol-17beta on expression of mRNA for seven angiogenic factors
      and their receptors in the endometrium of ovariectomized (OVX) ewes.
AB  - We have previously established an ovariectomized (OVX) ewe model to study how
      steroid removal and replacement affects uterine blood vessel and tissue growth.
      Using this model, endometrial expression of mRNA for 14 angiogenic factors (7
      genes and their respective receptors) in caruncular (CAR) and intercaruncular
      (ICAR) endometrium were evaluated by quantitative real time RT-PCR at 0
      (control), 2, 4, 8, 16, or 24 h after treating OVX ewes with an estradiol-17beta
      (E2) implant. In CAR and ICAR, compared to 0 h, the mRNA expression of vascular
      endothelial growth factor (VEGF), VEGF receptor (R)1, soluble guanylate cyclase
      (GUCY1B3; the R for nitric oxide [NO]), hypoxia inducible factor (HIF)1alpha, and
      placental growth factor (PlGF) increased by 4 h after E2-treatment, but basic
      fibroblast growth factor (FGF2), endothelial NO synthase (NOS3), angiopoietin
      (ANGPT)1, ANGPT2, ANGPT receptor Tie2 by 2 h after E2. Expression of mRNA for
      FGFR2 IIIc was increased at 2 h by E2-treatment in ICAR, but not in CAR. By
      contrast, expression of neuropilin (NP)1 mRNA was increased at 2 h in CAR, but
      not ICAR. The mRNA expression of VEGF, FGF2, HIF1 alpha, and PlGF was positively
      correlated with mRNA expression of NOS3, VEGFR1, and Tie2 suggesting some E2
      stimulated interactions between these factors in promoting blood vessel growth.
      Thus, several major angiogenic factors and their receptors are increased within
      hours after E2-treatment, which indicates that E2 plays a role in regulation of
      angiogenesis in the uterus. By using the OVX ewe model, we may begin to
      understand the molecular basis of E2 effects on angiogenesis in the endometrium
      and, eventually, how angiogenesis is regulated in normal versus pathological
      conditions.

PMID- 17526947
TI  - Mutation of phenylalanine-34 of parathyroid hormone disrupts NHERF1 regulation of
      PTH type I receptor signaling.
AB  - Internalization of the PTH type I receptor (PTH1R) is regulated in a cell- and
      ligand-specific manner. We previously demonstrated that the sodium/proton
      exchanger regulatory factor type 1 (NHERF1; EBP50) is pivotal in determining the
      range of peptides that internalize the PTH1R. Antagonist PTH fragments can
      internalize the PTH1R in some kidney and bone cell models. PTH(7-34), which binds
      to, but does not activate, the PTH1R, internalizes the PTH1R in kidney distal
      tubule (DT) cells, where NHERF1 is not expressed. The effect of antagonist PTHrP
      peptides has not, to this point, been assessed. PTH1R internalization was
      measured by real-time confocal fluorescence microscopy of DT cells stably
      expressing 105 EGFP-tagged PTH1R/cell. PTHrP(7-34) internalized the PTH1R in a
      manner indistinguishable from PTH(7-34). Introduction of NHERF1 into DT cells,
      however, blocked PTH(7-34)-, but not PTHrP(7-34)-, induced PTH1R internalization.
      To delineate the sequences within PTHrP that determine whether PTH1R
      internalization is affected by NHERF1, chimeric PTH/PTHrP fragments were tested
      for their ability to induce PTH1R internalization. PTH(7-21)/PTHrP (22-34), PTH(7
      32)/PTHrP(33-34), and PTH(7-33)/PTHrP(34) at 1 microM each internalized the PTH1R
      50-70% in a NHERF1-independent manner. When the C terminus of PTHrP was replaced
      with homologous amino acids from PTH, NHERF1 inhibited PTH1R internalization. It
      was determined that simply mutating F34 to A in PTH induced PTH1R internalization
      in a NHERF1-independent manner. None of the chimeric peptides activated the PTH1R
      but all effectively competed for 1 nM PTH(1-34) in cyclic AMP assays. In
      addition, all chimeric peptides competed for radiolabeled PTH(1-34) in binding
      assays in DT cells. PTH(1- 34) and PTHrP(7-34), but not PTH(7-34), efficiently
      recruited beta-arrestin1 to plasma membrane PTH1Rs. We, therefore, conclude that
      PTH(1-34) and PTHrP(7-34) induce a conformational change in the PTH1R that
      promotes arrestin binding and dissociates NHERF1 from PTH1R internalization.

PMID- 17526948
TI  - Stimulus-secretion coupling of hypotonicity-induced insulin release in BRIN-BD11
      cells.
AB  - The stimulus-secretion coupling for hypotonicity-induced insulin release was
      investigated in BRIN-BD11 cells. A 50 mM decrease in extracellular NaCl caused a
      twofold increase in insulin release. The release of insulin evoked by
      hypotonicity progressively decreased in an exponential manner. The response to
      extracellular hypotonicity displayed a threshold value close to 20 mOsmol/L and a
      maximal response at about 70 mOsmol/ L. Hypotonicity also caused a rapid increase
      in cell volume followed by a regulatory volume decrease (RVD), cell membrane
      depolarization with induction of spike activity, and a rise in cytosolic Ca2+
      concentration. 5-Nitro-2-(3-phenylpropylamino)benzoate inhibited the secretory
      response to hypoosmolarity, failed to affect the early increase in cell volume
      but prevented the RVD, and suppressed the hypotonicity-induced plasma membrane
      depolarization. Insulin release provoked by hypotonicity was inhibited by
      verapamil, absence of Ca2+, thapsigargin, furosemide, tributyltin, and diazoxide.
      On the contrary, tolbutamide augmented modestly insulin release recorded in the
      hypoosmolar medium. Last, a rise in extracellular K+ concentration, while
      augmenting basal insulin output, failed to affect insulin release in the
      hypoosmolar medium. Thus, the insulin secretory response to hypotonicity
      apparently represents a Ca2+-dependent process triggered by the gating of volume
      sensitive anion channels with subsequent depolarization and gating of voltage
      sensitive Ca2+ channels.

PMID- 17526949
TI  - The natural history of the R120C PROP1 mutation reveals a wide phenotypic
      variability in two untreated adult brothers with combined pituitary hormone
      deficiency.
AB  - BACKGROUND: Combined pituitary hormone deficiency (CPHD) corresponds to impaired
      production of growth hormone (GH) and other anterior pituitary hormones. The
      genetic form of CPHD may result from mutations in pituitary transcription factor
      genes, and PROP1 is the most commonly mutated gene in these cases. Patients with
      PROP1 mutations may have variable CPHD phenotypes but, because they are usually
      treated in childhood, the wide phenotypic variability caused by these mutations
      may not be thoroughly appreciated. METHODS: Clinical follow-up and molecular
      analysis of PROP1 in two adult brothers with CPHD, born from consanguineous
      parents, and not treated until late adulthood. RESULTS: The homozygous R120C
      mutation was identified in the brothers. Their clinical follow-up showed a wide
      phenotypic variability: hypogonadism was severe and prevented pubertal
      development in both, but their final heights were remarkably different, pointing
      to different degrees in severity of GH/TSH deficiencies; cortisol deficiency
      developed late in both, but at least 10 yr apart. CONCLUSIONS: The lack of
      treatment in childhood and adolescence allowed the appreciation of the entire
      natural history of the CPHD caused by the R120C mutation, and it revealed a
      remarkable phenotypic variability even in siblings with a very similar genetic
      background.

PMID- 17526950
TI  - Interleukin-6 production and deregulation of the hypothalamic-pituitary-adrenal
      axis in patients with major depressive disorders.
AB  - The present study was designed to determine whether an association exists between
      HPA activity and cytokine production in major depression (MD). In 9 patients with
      MD and 11 control subjects of both sexes, all drug-free, activity of the HPA axis
      was evaluated by circadian rhythm of plasma cortisol, 24-h free urinary cortisol,
      an overnight 1 mg dexamethasone suppression test, and an oCRF stimulation test.
      Spontaneous and LPS-stimulated production of IL-1beta, IL-6, and TNFalpha by
      peripheral blood mononuclear cells were also determined. We found a significantly
      elevated spontaneous production of IL-6 in patients with MD (3541.2 +/- 726.8 vs
      380.4 +/- 77.5 pg/mL in controls, p < 0.05), while LPS-stimulated production was
      significantly lower in patients than in control subjects (19,867.7 +/- 3649.2 vs
      33,142.2 +/- 15,47.2 pg/mL, p < 0.05). The adrenocorticotropic hormone response
      to oCRF, evaluated as the area under the curve (AUCACTH) was significantly lower
      in patients than in control subjects (p = 0.02). A positive correlation between
      AUCACTH and LPS-stimulated IL-6 secretion was observed in patients with MD (r =
      0.75, p < 0.05) but not in controls. These findings suggest that the activation
      of the inflammatory response described in depression might be associated with
      long-term hyperactivity of the HPA axis.

PMID- 17526951
TI  - The predictive value of CTLA-4 and Tg polymorphisms in the recurrence of Graves'
      disease after antithyroid withdrawal.
AB  - Graves' disease (GD) is a multifactorial disease that develops as a result of
      complex interactions between genetic and environmental factors. The aim of our
      study is to determine the frequency of cytotoxic T-lymphocyte- associated antigen
      4 (CTLA-4) A/G and TG C/T exon 33 SNPs (Tg E33SNP) in GD and to evaluate the
      relation between recurrence and these polymorphisms. A total of 187 subjects,
      including 97 previously treated GD patients and 90 age and gender matched control
      subjects were studied. We examined the relationship between the A/G and C/T
      polymorphism and various clinical and laboratory variables among patients with
      GD. TT genotype frequency in the GD patients was significantly higher than the
      controls. Number of recurrent patients was significantly higher in AG and GG
      carriers in comparison to AA carriers (57% and 45% vs 14%, p = 0.0001). CTLA-4 AG
      genotype had an eightfold (OR: 8.050; 95% CI: 2.87-22.5; p = 0.0001) and GG
      genotype had a sevenfold (OR: 7.025; 95% CI: 1.67-29.4; p = 0.007) increase in
      the risk of recurrence in the patients with GD. In conclusion, early
      interpretation for definitive treatment procedures (i.e., radioactive iodine or
      surgery) may be considered in the patients with G allele and E33SNP of Tg gene is
      conformed the susceptibility to GD in a Turkish population and having TT genotype
      increases the susceptibility to GD.

PMID- 17526952
TI  - Clinical significance of heterozygous carriers associated with compensated
      hypothyroidism in R450H, a common inactivating mutation of the thyrotropin
      receptor gene in Japanese.
AB  - Loss-of-function mutations in the thyrotropin receptor (TSHR) gene were described
      as a syndrome characterized by thyroid hyposensivity to biologically active TSH,
      ranging from euthyroid to severe hypothyroidism. In Japanese, a common mutation
      in the TSHR gene is R450H, which demonstrated moderately impaired receptor
      function. We studied six subjects of Japanese origin whose major abnormality was
      persistent hyperthyrotropinemia by genetic sequence analysis of the TSHR gene.
      Three subjects were homozygous for the R450H mutation, whereas the three
      remaining subjects were single heterozygous. Homozygous subjects displayed mild
      hypothyroidism confirmed by moderately elevated basal TSH levels and excessive
      TSH response to TRH administration. Heterozygous subjects also demonstrated fully
      or partially compensated hypothyroidism, but less severe than that of homozygous
      subjects. More frequent involvement of the R450H mutation in the TSHR gene in
      Japanese was identified. In addition, a good correlation between phenotype and
      genotype was demonstrated in respect to biochemical analysis and drug dosage. Our
      observations showed clinical significance of heterozygosity associated with
      compensated hypothyroidism in spite of only mildly impaired receptor function.

PMID- 17526953
TI  - Association of adrenal medullar and cortical nodular hyperplasia: a report of two
      cases with clinical and morpho-functional considerations.
AB  - Arterial hypertension of adrenal etiology is mainly attributed to primary
      hyperaldosteronism. However, subtle expressions of hyperadrenergic or
      glucocorticoid excess can also generate arterial hypertension. The present report
      describes two hypertensive patients cataloged as resistant essential
      hypertensives, in whom adrenal masses were found incidentally, who highlight the
      need to recognize these tenuous clinical or laboratory presentations. Case 1 was
      a 50-yr-old female with hyperadrenergic hypertension associated to a left adrenal
      node, normal cortisol and aldosterone:renin ratio, marginally increased urinary
      normetanephrine, and a positive 131I MIBG radioisotope scan. Adrenalectomy
      normalized blood pressure and urinary metanephrines. Pathology showed a
      hyperplastic adrenal medulla associated to a multinodular cortical hyperplasia.
      Case 2 was a 62- yr-old female with progressive hypertension, a slight Cushing
      phenotype, non-suppressible hypercortisolism, normal urinary metanephrines, and
      bilateral adrenal nodes. Bilateral adrenalectomy and subsequent replacement
      normalized blood pressure and phenotypic stigmata. Pathology demonstrated
      bilateral cortical multinodular hyperplasia and medullary hyperplasia. The
      clinical study in both patients was negative for MEN. The apparently rare
      association of cortical and medullary lesions presented by both patients is
      probably overlooked in routine pathology exams, but should be meticulously
      searched since the crosstalk between the adrenal cortex and medulla may prompt
      dual abnormalities.

PMID- 17526954
TI  - Impact of mass supplementation of vitamin A.
AB  - OBJECTIVE: To study the impact of mass supplementation of Vitamin A solution on
      morbidity due to diarrhea, Acute respiratory infection (ARI) and xerophthalmia.
      METHODS: The two rounds of age specific mass distribution of Vitamin A solution
      were undertaken during January 2000 and December 2000 respectively covering
      27,642 (98.7%) and 31,762 (88.0%) children respectively out of total
      beneficiaries in two round of PPI in Chandigarh. A random sample of 276 children
      from intervention area and 252 children from control area in the age group of 1-5
      yr were followed up on monthly basis for morbidity pattern for a period of nine
      mth. The morbidity pattern for intervention and control area children was
      compared to see the impact of mass supplementation of Vitamin A solution.
      RESULTS: The average annual episodes of diarrhea in intervention children were
      lower (3.9 per yr) as compared to control children (5.2 per yr) although
      difference was not statistically significant (P>0.05) except in initial month.
      The average annual episodes of ARI in intervention children were lower (5.1 per
      yr) as compared to Control children (6.0 per yr) although difference was not
      significant (P>0.05) except in initial first mth. There was significant decline
      in vitamin A deficiency (VAD) as no case of Bitot's spot was found in
      intervention children as compared to control children where the prevalence of
      Bitot's spot ranged from 4.3-5.08% during different visits. The mortality rate
      was found to be higher in control children with a death rate of 8 per 1000
      children during the study period as compared to intervention children where no
      death was recorded. CONCLUSION: It is concluded that mass supplementation of
      vitamin A led to significant reduction in xerophthalmia and decline in mortality
      in the intervention area as compared to control area.

PMID- 17526955
TI  - Infant mortality in an urban slum.
AB  - OBJECTIVE: Infant and child mortality are important indicators of the level of
      development of a society, but are usually collected by governmental agencies on a
      region wide scale, with little local stratification. In order to formulate
      appropriate local policies for intervention, it is important to know the patterns
      of morbidity and mortality in children in the local setting. METHODS: This
      retrospective study collected and analyzed data on infant mortality for the
      period 1995 to 2003 in an urban slum area in Vellore, southern India from
      government health records maintained at the urban health clinic. RESULTS: The
      infant mortality rate over this period was 37.9 per 1000 live births. Over half
      (54.3%) of the deaths occurred in the neonatal period. Neonatal deaths were
      mainly due to perinatal asphyxia (31.9%), pre-maturity (16.8%) and aspiration
      pneumonia or acute respiratory distress (16.8%), while infant deaths occurring
      after the first mth of life were mainly due to diarrheal disease (43%) and
      respiratory infections (21%). CONCLUSION: These results emphasize the need to
      improved antenatal and perinatal care to improve survival in the neonatal period.
      The strikingly high death rate due to diarrheal illness highlights the
      requirements for better sanitation and water quality.

PMID- 17526956
TI  - Drug dependence in adolescents 1978-2003: a clinical-based observation from North
      India.
AB  - OBJECTIVE: To study the demographic and clinical profile of adolescent subjects
      (< or =18 yr) presenting to a state-funded drug de-addiction centre in north
      India. METHODS: Data on demographic and clinical features were extracted from
      available case notes of adolescent patients who presented to the centre during
      1978-2003 (n=85). RESULTS: Many adolescents came from nuclear family (63.5%), of
      urban background (83.5%) and were school dropouts (54.1%). Mean age-at-first-use
      of the primary substance was 14.8 yr and mean age at first presentation was 17
      yr. The commonest used primary class of substance was opioids (76.2%) and the
      commonest used opioid was heroin (36.5%). More than half of the subjects (54.2%)
      were also nicotine dependent at the time of presentation. The most common reason
      for starting the use of drugs was curiosity (78.8%). About one-fifth (21.2%) of
      the subjects indulged in high-risk behaviour such as having sexual intercourse
      with multiple sexual partners. Nearly half of the subjects had positive family
      history of either drug dependence (40.2%) or psychiatric disorder (5.5%).
      CONCLUSION: The results suggest that the development of substance dependence in
      children and adolescents is a combination of familial and social vulnerability
      factors, including the drug culture of the social milieu.

PMID- 17526957
TI  - Plasma protein variations in hemophiliacs receiving factor replacement therapy.
AB  - OBJECTIVE: Post transfusion manifestations and its affiliated factors are vital
      to understand in a disease like hemophilia where multi-transfusions are given to
      the patients. METHODS: To investigate the implications of factor replacement
      therapy on plasma proteins, 52 hemophiliacs and 68 carrier females were examined
      for 12 plasma proteins using various electrophoretic techniques. RESULTS: Severe
      hemophiliacs showed raised levels ( p< 0.05) of a2 M, IgG and Albumins where
      values were found to be 4.78 +/- 0.865 g/l, 21.48 +/- 3.38 g/l, 66.26 +/- 11.92
      g/l respectively at 95% confidence intervals however, controls and carriers
      showed trivial variations. CONCLUSION: Juxtaposing the dissimilarities of 12
      plasma proteins in carriers, controls and hemophiliacs, it has been gleaned that
      factor replacement therapy do play role when seen in severe hemophiliacs with
      raised levels.

PMID- 17526958
TI  - Multiple courses of antenatal steroids.
AB  - The benefits and risks of multiple courses of antenatal steroids (ANS) are still
      unresolved issues. This was a prospective cohort study in a level III neonatal
      unit. Preterm babies < or = 35 wk gestation were included. Malformations, chronic
      maternal steroid intake, exchange transfusions prior to cortisol sampling and
      incomplete ANS courses were exclusion criteria. Subjects were classified into: No
      course (Group 0), 1 course (group 1), 2 courses (Group 2), > 2 courses (Group 3)
      of antenatal dexamethasone. The key outcome was adrenal function assessed by
      basal and post-ACTH cortisol on day 3. Other outcomes were neonatal morbidity,
      mortality, growth parameters at birth, long term growth and neuro-development. Of
      210 eligible babies, 124 were enrolled. 38, 51, 10 and 25 babies belonged to
      groups 0, 1, 2 and 3 respectively. Basal and post-ACTH serum cortisol did not
      show any significant difference between groups (p=0.5 and p=0.9 respectively).
      Incidence of severe HMD requiring ventilation was significantly lower (p=0.02) in
      multiple course group (combined groups 2 and 3) compared to single course group.
      There were no differences in other neonatal morbidity, birth OFC and weight
      between single and multiple ANS groups. Follow up data at a mean age of 22 mth
      was available in 59 subjects (69%) belonging to groups 1-3. No differences were
      noted in the proportion of patients with abnormal neurological examination
      (p=0.1), abnormal PDI (p=0.9), abnormal MDI (p=0.9) and physical growth between
      multiple and single course groups. Multiple courses of antenatal dexamethasone
      resulted in a significant decrease in severe forms of RDS and they did not cause
      adrenal suppression, decreased growth or impaired neuro-development.

PMID- 17526959
TI  - An evaluation of diarrheal diseases and acute respiratory infections control
      programmes in a Delhi slum.
AB  - OBJECTIVE: Effective early management at home level and health seeking behavior
      in case of appearance of danger signs are key strategies in Acute respiratory
      Infections (ARI) and Acute Diarrheal Diseases (ADD) where majority of episodes
      are self-limiting and viral in origin. Integrated Management of Childhood
      illnesses (IMNCI) also envisages that family and community health practices
      especially health care seeking behaviors are to be improved to reduce childhood
      morbidity, mortality and cost of admissions to hospitals. Thus, a study was
      undertaken at an urban slum area--'Gokul Puri' in Delhi, among under-5 children
      with the aim to assess the magnitudes of ARI and ADD. METHODS: A Cross-sectional
      survey was conducted in this urban slum of Trans-Yamuna, covering 1307 under-5
      children for five days starting from 9th of August, 2004. Survey team consisted
      of 14 FETP Participants (WHO Fellows) from India, Nepal, Myanmar, Bhutan and Sri
      Lanka. A pre-tested, house-hold tally marking form was used to interview the
      caretakers/mothers. History of episodes of ARI and/or ADD in the last two weeks
      was asked. Health care practices including use of ORS &home available fluids in
      diarrhea, continued feeding during diarrhea, awareness of danger signs of ARI
      &ADD and medical advice sought were asked of those mothers whose children had
      such an episode. RESULTS: 191 (14.6 %) of 1307 children surveyed, had an attack
      of ARI in the preceding two wk. The common symptoms of ARI cases were mild
      running nose (78%), cough (76.4%) and/or fever (45.5%). Only 8 (4%) had fast
      breathing. One or more danger signs were known to 80% (152/191) of mothers and an
      equal number (80%) of mothers had sought treatment. ARIs are mostly mild or self
      limiting but only 16% of caretakers perceived so and doctors also prescribed
      medicines. The attack rate of Acute Diarrheal Diseases was 7.73% in the study and
      ADD's annual adjusted morbidity rate was 1.69 episodes per child per year. Though
      nearly three-fourth of mothers (71.3%) had reported to be seeking medical advice
      (which is not needed in mild episodes of diarrhea) the ORS use was 38.6%, use of
      Home available fluids (HAF) was 42% and continued feeding was 50% during the ADD
      episode and awareness of at least two danger signs was present in 34%.
      CONCLUSION: Though aware of danger signs of ARI, care takers were still seeking
      medical advice for mild cases of ARI and doctors were prescribing drugs. Correct
      home based management e.g. use of ORS, continued feeding etc. was deficient in
      the community. Knowledge of danger symptoms was low and medical advice was being
      sought and drugs were being prescribed for ADD, too.

PMID- 17526960
TI  - Modifiable risk factors for acute lower respiratory tract infections.
AB  - OBJECTIVE: Acute respiratory infection is a leading cause of morbidity and
      mortality in under five children in developing countries. Hence, the present
      study was undertaken to identify various modifiable risk factors for acute lower
      respiratory tract infections (ALRI) in children aged 1 mth to 5 yr. METHODS: 104
      ALRI cases fulfilling WHO criteria for pneumonia, in the age group of 1 mth to 5
      yr were interrogated for potential modifiable risk factors as per a predesigned
      proforma. 104 healthy control children in the same age group were also
      interrogated. RESULTS: The significant sociodemographic risk factors were
      parental illiteracy, low socioeconomic status, overcrowding and partial
      immunization, [p value < 0.05 in all]. Significant nutritional risk factors were
      administration of prelacteal feeds, early weaning, anemia, rickets and
      malnutrition, [p value < 0.05 in all]. Significant environmental risk factors
      were use of kerosene lamps, biomass fuel pollution and lack of ventilation [p
      value < 0.05 in all]. On logistic regression analysis, partial immunization,
      overcrowding and malnutrition were found to be significant risk factors.
      CONCLUSION: The present study has identified various socio-demographic,
      nutritional and environmental modifiable risk factors for ALRI which can be
      tackled by effective education of the community and appropriate initiatives taken
      by the government.

PMID- 17526961
TI  - Negative pressure ventilation in pediatric critical care setting.
AB  - Invasive ventilation is associated with both pulmonary and non-pulmonary
      complications. There has been a renewed interest in the use of negative pressure
      ventilation (NPV) for various medical conditions to minimise the complications
      associated with positive pressure ventilation. The routine use of NPV in an ICU
      setting still requires further studies and research. In this article, the authors
      review the clinical applications of NPV together with associated risks and
      limitations. Case reports of patients with cardiac, neuromuscular and respiratory
      diseases managed with NPV on our unit are described. NPV improved the clinical
      condition in each of these patients and decreased the requirement for invasive
      therapy.

PMID- 17526962
TI  - Fulminant hepatic failure complicating visceral leishmaniasis in an apparently
      immunocompetent child.
AB  - Fulminant hepatic failure (FHF) is an unusual complication of
      visceralleishmaniasis (VL). Here, we present a 1.5-yr-old girl with VL developing
      rapidly progressive fatal FHF. In absence of established guidelines, additional
      use of immunomodulatory therapies has been discussed in reference to available
      information.

PMID- 17526963
TI  - Hashimoto's encephalopathy in an adolescent boy.
AB  - Hashimoto's encephalopathy is an under-recognized cause of acute encephalopathy
      both in children and adults. We hereby describe a 12.5 yr old boy with this rare
      disorder that presented with an acute onset of episodic psychosis with
      hallucinations along with seizures and had elevated antithyroid antibodies.
      Symptoms improved with thyroxine replacement and anticonvulsants and EEG
      normalized 3 mth into follow up. Hashimoto's encephalopathy should be considered
      in patients with unexplained encephalopathy and seizures, as prompt recognition
      and management can lead to an excellent outcome.

PMID- 17526964
TI  - Rubella infection with autoimmune hemolytic anemia.
AB  - A 4-yr-old boy developed autoimmune hemolytic anemia after rubella infection and
      clinical manifestations cleared up after decrease in rubella specific IgM titer
      without any specific therapy.

PMID- 17526965
TI  - May thrombosis be a cause of congenital extremity absence?
AB  - Congenital extremity anomalies have many modes of presentation. Interruption of
      vascular supply with thrombophily is a rare cause of congenital extremity
      absence. Here it is presented a 7 mth old male with absence of the left lower
      extremity. Laboratory tests revealed Factor V Leiden and Prothrombin G20210A
      heterozygote mutation and that was as the cause of extremity absence. At the
      patients with congenital extremity absences, it is not imprudent to explore a
      possible thrombophilic mutation along with other known etiologic factors.

PMID- 17526966
TI  - Omphalomesenteric duct cyst as a content of omphalocele.
AB  - A rare occurrence of an omphalomesenteric duct cyst in an exomphalos minor sac is
      reported herein. The noteworthy points in this case were an unusual presentation
      of the rarest variety of umbilical cord cyst. The tapering intra-abdominal end of
      the cyst was found to be attached to the ileal mesentry, thereby simulating a
      herniating mesenteric cyst till the histolopathological report resolved the
      issue.

PMID- 17526967
TI  - Bilateral eventration of the diaphragm with malrotation and unilateral renal
      agenesis.
AB  - Bilateral eventration of the diaphragm associated with malrotation of gut and
      unilateral renal agenesis is a very rare entity. The authors treated a seven mth
      old male child who presented to them with respiratory distress and
      gastrointestinal problem. The child was anemic and was in type II respiratory
      failure. His X-ray chest showed bilateral eventration of diaphragm and
      ultrasonography abdomen was consistent with left renal agenesis which was
      confirmed by radionuclide scan. Bilateral plication of the diaphragm done with
      correction of malrotation which was diagnosed peroperatively. The association of
      these three anomalies are rare and to be kept in mind whenever treating a patient
      with bilateral eventration of the diaphragm.

PMID- 17526968
TI  - Bleomycin induced hyperpigmentation with yolk sac tumor.
AB  - Hyperpigmentation is one of the cutaneous side effects of chemotherapautic
      agents, but it is usually accepted as a cosmetic problem. We report a child with
      yolk sac tumor who developed localized pigmentation after the first course of
      chemotherapy regimen that included cisplatin, etoposide and bleomycin. The
      hyperpigmentation was diffuse scattered, flagellate like and linear streaking
      which was thought to be mainly related to the skin toxicity of bleomycin.

PMID- 17526969
TI  - Ring chromosome 9 in a dysmorphic child.
AB  - Ring chromosome is a rare genetic disorder observed in the children with variable
      clinical presentation and phenotype. Among several ring formation, individuals
      with r(9) generally have less distinct clinical features. An eight-mth-old boy,
      presenting with broad and dark eyebrows with protruding tongue, microcephaly,
      short stature and failure to thrive was found to have ring chromosome 9.
      46,X,inv(Y),r(9)(p24q34). This shows that karyotype study is an essential
      integral investigation in the management of dysmorphic child.

PMID- 17526970
TI  - Spontaneous biliary perforation in infancy and childhood: clues to diagnosis.
AB  - Spontaneous perforation of extrahepatic bile duct is rare. The cause is
      idiopathic once trauma and choledochal cyst are ruled out. The condition presents
      a diagnostic dilemma. Preoperative recognition is necessary as early surgical
      intervention gives excellent prognosis. We report clinical observations made in
      three cases with acute presentations. Diagnosis is to be suspected by the
      presence of jaundice after an initial anicteric period of good health with
      biliary ascites. This is confirmed by bilious abdominal paracentesis, signs of
      peritonitis and absent free gas on X ray. The constellation of these three
      findings was constant in three patients. The presented paper highlights the same
      as reliable clues to diagnosis.

PMID- 17526971
TI  - Effects of exchange transfusion on neonatal thyroid function.

PMID- 17526972
TI  - Factors affecting antibiotic prescribing pattern in pediatric practice.

PMID- 17526973
TI  - Effect of combined cardiovascular risk factors on individual and population
      medical expenditures: a 10-year cohort study of national health insurance in a
      Japanese population.
AB  - BACKGROUND: Although obesity is required for some criteria defining metabolic
      syndrome, clustering of other risk factors also indicates an increased risk of
      cardiovascular disease. Whether the relationship between cardiovascular risk
      factor clustering and medical expenditures differs with body mass index (BMI)
      requires investigation, especially in a population with a low prevalence of
      obesity such as that in Japan. METHODS AND RESULTS: A 10-year cohort study of
      4,478 Japanese National Health Insurance beneficiaries aged 40-69 years in a
      community between 1990 and 2001 was carried out in the present study. The
      clustering of cardiovascular risk factors showed a positive and graded
      relationship to personal medical expenditures in participants who are overweight
      (BMI > or =25.0) and normal weight (BMI <25.0). The individual medical
      expenditures per month were 1.7-fold higher for participants with 2 or 3 risk
      factors and overweight than for those without these factors (26,782 vs 15,377
      Japanese yen). Differences in the geometric means were similarly significant
      after adjustment for other confounding factors. However, the excess medical
      expenditures by risk clustering of normal weight categories within the total
      medical expenditures were higher than those of overweight categories because more
      participants were of normal weight. CONCLUSIONS: Cardiovascular risk factor
      clustering and being overweight can be a useful predictor of medical expenditures
      in a Japanese population.

PMID- 17526974
TI  - Mortality risk attributable to atrial fibrillation in middle-aged and elderly
      people in the Japanese general population: nineteen-year follow-up in NIPPON
      DATA80.
AB  - BACKGROUND: The extent to which atrial fibrillation (AF) contributes to mortality
      in the Japanese general population has not been clarified. METHODS AND RESULTS: A
      randomly sampled general population from all over Japan (4,154 men, 5,329 women;
      age > or =30 years) was enrolled. Single electrocardiogram recordings were taken
      in the baseline survey. Stroke death, cardiovascular deaths and all-cause deaths
      during the subsequent 19 years were analyzed by the presence of AF at baseline.
      Cox's regression analysis was carried out to estimate the hazard ratios (HRs) of
      each cause of death attributable to AF after adjusting for other risk factors.
      Prevalence of AF was 0.64% in the study. The observed person-years were 162,980
      among persons without AF and 699 among persons with AF. There were 1,919 deaths.
      Multivariate adjusted HRs for stroke death, cardiovascular death and all-cause
      death were 2.69, 2.76 and 1.88, respectively (p<0.05). These HRs were 14.7, 9.63
      and 4.00 among persons aged 64 years or younger (p<0.05). CONCLUSION: AF affects
      stroke mortality, cardiovascular mortality and all-cause mortality in the
      Japanese general population. Careful attention should be paid to persons with AF
      in order to prevent future cardiovascular events.

PMID- 17526975
TI  - High-sensitivity C-reactive protein is quite low in Japanese men at high coronary
      risk.
AB  - BACKGROUND: Although numerous studies have demonstrated a positive association of
      high-sensitivity C-reactive protein (CRP) with the incidence of coronary heart
      disease (CHD), little information exists regarding this issue in Japanese.
      METHODS AND RESULTS: The association between CRP and the Framingham Risk Score
      (FRS) was investigated in 2,523 middle-aged Japanese men without a medical
      history of CHD. CRP was significantly associated with this score obtained from
      all FRS factors. After dividing subjects into 4 categories of relative risk
      estimate for CHD, the geometric mean of CRP (mg/L) increased gradually with the
      CHD risk (below average: 0.39 [95% confidence interval, 0.37-0.41], average: 0.58
      [0.50-0.67], moderately above average: 0.70 [0.57-0.86], high: 0.79 [0.58-1.09],
      trend p<0.001). However, it should be noted that the mean CRP concentration of
      the high-risk group was only 0.79 mg/L and a greater proportion (63.8%) of the
      high-risk subjects was in the low-risk range of CRP (<1 mg/L). CONCLUSIONS:
      Circulating CRP well reflect the estimated CHD risk, indicating that CRP may be
      useful for coronary risk stratification in Japanese also. However, the details of
      the CRP level in Japanese must be investigated further by prospective studies to
      determine the Japanese-specific cutoff points for CHD risk evaluation.

PMID- 17526976
TI  - Double-blind, multicenter, active-controlled, randomized clinical trial to assess
      the safety and efficacy of orally administered nicorandil in patients with stable
      angina pectoris in China.
AB  - BACKGROUND: The efficacy and safety of nicorandil were evaluated in Chinese
      patients with stable angina pectoris (AP) in a double-blind, multicenter, active
      controlled, randomized clinical trial. METHODS AND RESULTS: After a 2-week
      washout period, 232 patients with stable AP were randomized to receive either
      nicorandil (5 mg tid; 115 patients) or isosorbide mononitrate (ISMN: 20 mg bid;
      117 patients) for 2 weeks. Exercise capacity, number of weekly anginal attacks,
      nitroglycerin (NTG) consumption, and safety were evaluated. Nicorandil and ISMN
      significantly prolonged the time to 1 mm ST-segment depression in an exercise
      tolerance test. Both drugs improved the total exercise time and the time to onset
      of chest pain. There was no significant difference between the 2 groups.
      Nicorandil significantly decreased the number of anginal attacks and NTG
      consumption. ISMN decreased the number of anginal attacks significantly; however,
      there was no significance in NTG consumption, and the ratio of anginal attack
      reduction was at least 50% was significantly higher with nicorandil. Nicorandil
      was well tolerated and there was no safety profile difference compared with ISMN.
      Thus, nicorandil may have equivalent or better antianginal effect than ISMN.
      CONCLUSIONS: Nicorandil is beneficial as treatment for AP.

PMID- 17526977
TI  - Impact of newly diagnosed abnormal glucose tolerance on long-term prognosis in
      patients with acute myocardial infarction.
AB  - BACKGROUND: Newly-diagnosed diabetes mellitus (DM) and impaired glucose tolerance
      are common among patients with acute myocardial infarction (AMI). However, its
      significance on long-term clinical outcomes in those patients remains unclear.
      The present study was designed to determine whether such abnormalities after AMI
      affect long-term clinical outcomes. METHODS AND RESULTS: Two-hundred and seventy
      five AMI patients were prospectively enrolled. Eighty-five had diagnosed DM,
      while the other 190 did not. According to oral glucose tolerance tests at
      discharge, non-DM patients were divided into 2 groups: 78 patients with normal
      glucose tolerance and 112 patients with abnormal glucose tolerance. Patients were
      followed until they reached the primary endpoint: cardiovascular death or
      unplanned hospitalization due to major adverse cardiovascular events. The median
      follow-up period was 5.3 years. Kaplan-Meier survival curves for the abnormal
      glucose tolerance group were poorer than for normal glucose tolerance, and were
      equivalent to the pre-diagnosed DM group in prognosis (p<0.0005). Glucometabolic
      status was the strongest predictor for future cardiovascular events (hazard ratio
      to normal glucose tolerance; 2.65; confidence interval: 1.37-5.15; p=0.004 in
      abnormal glucose tolerance and 3.27:1.68-6.38; p=0.0005 in DM). CONCLUSIONS:
      Abnormal glucose tolerance in patients with AMI is a major risk factor for future
      cardiovascular events and may critically distinguish high-risk individuals.

PMID- 17526978
TI  - Endothelial lipase gene polymorphism is associated with acute myocardial
      infarction, independently of high-density lipoprotein-cholesterol levels.
AB  - BACKGROUND: Endothelial lipase (EL) is a major determinant of high-density
      lipoprotein-cholesterol (HDL-C) metabolism and promotes monocytes recruitment.
      The local expression of EL could influence atherogenesis directly, in addition to
      its systemic role in HDL metabolism. The EL gene has a common 584C/T
      polymorphism, but it is unclear whether this polymorphism is associated with HDL
      C levels or acute myocardial infarction (AMI). METHODS AND RESULTS: A case
      control study of 107 AMI patients and 107 control subjects was conducted. T
      allele frequency was lower in the AMI group than in controls (0.18 vs 0.26,
      p<0.05). No significant association was found between the 584C/T polymorphism and
      HDL-C levels. Multivariate regression analyses showed that the association of the
      T allele with AMI was statistically significant and independent of other risk
      factors when age, sex, hypertension, hypercholesterolemia, and diabetes mellitus
      were included in the analyses (odds ratio (OR), 0.52; 95% confidence interval
      (95% CI) 0.28-0.98; p=0.04). However, when smoking status was included, the
      association of the T allele with AMI did not remain statistically significant
      (OR, 0.61; 95% CI 0.32-1.18; p=0.14). CONCLUSIONS: The 584C/T polymorphism of the
      EL gene was associated with AMI independently of HDL-C levels and thus may be
      involved in the pathogenesis of AMI.

PMID- 17526979
TI  - Clinical outcome and quality of life of octogenarian patients following
      percutaneous coronary intervention or surgical coronary revascularization.
AB  - BACKGROUND: Thus far, the outcome and effect of percutaneous coronary
      intervention (PCI) or coronary artery bypass graft (CABG) surgery on the quality
      of life of octogenarian patients has not been accurately assessed in Japan.
      METHODS AND RESULTS: A retrospective analysis of the outcome of invasive coronary
      revascularization in 130 elderly patients (age, > or =80 years) with ischemic
      coronary disease was carried out. Their current quality of life was determined by
      the Seattle Angina Questionnaire. Although the in-hospital death rate was
      relatively high (21.6% after PCI and 14.3% after CABG surgery), the long-term
      outcome of the patients who did not die during the in-hospital period after the
      PCI/CABG surgery was acceptable (5-year survival rate, >60%). All domains of the
      questionnaire received a favorable score from a majority of the survivors,
      irrespective of the treatment they received. CONCLUSIONS: The quality of life and
      longevity of the octogenarian patients following extensive invasive
      revascularization for ischemic coronary artery disease were satisfactory.

PMID- 17526980
TI  - Feasibility and safety of transradial stenting for unprotected left main coronary
      artery stenoses.
AB  - BACKGROUND: Percutaneous coronary intervention (PCI) is considered an excellent
      alternative treatment for unprotected left main coronary artery (ULMCA) stenoses.
      Most PCIs for ULMCA stenoses are performed via the transfemoral approach. The
      feasibility and safety of the transradial approach for this particular entity are
      unknown. The present study assessed the feasibility, safety and 1-year outcomes
      of the transradial approach for stenting of ULMCA stenoses. METHODS AND RESULTS:
      Of 131 consecutive patients who underwent coronary stenting for ULMCA stenoses,
      113 patients (86.3%) received stenting using the transradial approach. All 113
      procedures were performed with 6 or 7 French (Fr) catheters except 1 procedure
      requiring an 8 Fr guiding catheter for directional atherectomy. The technical
      success rate was 100%, and angiographic success was achieved in 96 patients
      (85.9%). Two patients had local hematoma (1.8%), and no procedure-related deaths,
      Q-wave myocardial infarction, repetitive PCI, stroke or emergent coronary artery
      bypass graft surgery during hospitalization were noted. One (0.9%) in-hospital
      cardiac death occurred due to ventricular tachyarrhythmia. More than half of our
      patients stayed in hospital by < or =3 days. The 1-year target lesion
      revascularization and cardiac death rate were 14.2% and 3.5%, respectively.
      CONCLUSIONS: This investigation demonstrated the feasibility, safety and accepted
      short-term clinical outcomes of transradial stenting for ULMCA stenosis. This
      procedure may offer a feasible alternative to the transfemoral approach.

PMID- 17526981
TI  - Effects of the early administration of heparin in patients with ST-elevation
      myocardial infarction treated by primary angioplasty.
AB  - BACKGROUND: The effect of adjunctive heparin for primary angioplasty in patients
      with ST-elevation myocardial infarction (STEMI) is not well established, so the
      authors investigated the effect of early heparin administration in the emergency
      room (ER) on initial patency of the infarct-related artery (IRA) and on the
      clinical outcome in STEMI patients. METHODS AND RESULTS: One hundred and twenty
      consecutive patients who presented with STEMI less than 12 h from pain onset and
      who were eligible for primary percutaneous coronary intervention were allocated
      to an early heparin group (heparin administered in ER) or a late heparin group
      (heparin administered after angiography). In the early heparin group,
      unfractionated heparin (60 U/kg bolus IV, then 14 U . kg(-1) . h(-1) IV infusion)
      or enoxaparin (1 mg/kg bolus SC) were administered 144+/-95 min before
      angioplasty. No significant differences in baseline characteristics were observed
      between the early heparin group (n=56) and the late heparin group (n=64).
      However, initial Thrombolysis In Myocardial Infarction (TIMI) flow grade in the
      IRA was significantly different between the 2 groups (frequency of TIMI 0/1/2/3;
      48/4/7/41% vs 70/8/11/11%, early vs late respectively, p=0.002). TIMI 2 or 3 flow
      was significantly more frequent in the early heparin group than in the late
      heparin group (48% vs 22%, p=0.002). However, no significant differences were
      noted between the 2 groups in terms of in-hospital major adverse cardiac events
      (7% vs 11%, p=0.472) and TIMI major bleeding (2% vs 3%, p=0.639). CONCLUSIONS: In
      STEMI patients, early heparin therapy administered in the ER improves coronary
      patency, despite not reaching clinical benefit.

PMID- 17526982
TI  - Serum resistin as a biological marker for coronary artery disease and restenosis
      in type 2 diabetic patients.
AB  - BACKGROUND: Resistin is an adipocyte-secreted hormone. The relationship between
      circulating resistin concentrations and atherosclerotic coronary artery disease
      (CAD) in type 2 diabetic patients, if any, remains poorly understood. Serum
      resistin concentrations were investigated in type 2 diabetic patients with CAD
      (DMCAD), and compared with the concentrations in diabetics patients without CAD
      (diabetes mellitus, DM). Whether resistin levels are associated with increased
      restenosis rates in diabetic patients with CAD after successful coronary stenting
      was also investigated. METHODS AND RESULTS: Fasting serum resistin, adiponectin,
      and leptin concentrations were measured in 45 DMCAD patients and 47 DM controls.
      The percutaneous coronary intervention study included 70 DMCAD patients, who
      underwent elective and successful coronary bare metal stent (BMS) implantation
      for the treatment of de novo lesions. Serum resistin concentrations were higher
      in the DMCAD patients than in the DM controls (5.75+/-3.21 vs 2.53+/-2.47 ng/ml,
      mean +/- SEM, p<0.001), and these differences were persistent regardless of age
      or body mass index. Insulin resistance indices, as assessed via homeostasis model
      assessment (HOMA-IR) correlated significantly with resistin concentrations
      (r=0.4, p<0.001). Resistin was an independent factor, and was associated with
      DMCAD in the multivariate analysis. In the percutaneous coronary intervention
      study, HOMA-IR was not associated with subsequent restenosis rates after BMS
      implantation in DMCAD patients. Pre-procedural serum resistin concentrations were
      higher in restenosis group than in the patients without restenosis. CONCLUSIONS:
      Serum resistin may prove to be a useful biological marker for CAD and restenosis
      in patients with type 2 DM.

PMID- 17526983
TI  - Randomized comparison of bipolar vs unipolar plus bipolar recordings during
      atrioventricular junction ablation: importance and efficacy of unipolar
      recording.
AB  - BACKGROUND: No prior studies have clarified the utility and efficacy of unipolar
      recording for identifying successful sites for atrioventricular junction (AVJ)
      ablation. METHODS AND RESULTS: Thirty-six patients underwent radiofrequency (RF)
      AVJ ablation for drug-resistant atrial fibrillation (AF) or AF/flutter. AVJ
      ablation was performed with either bipolar (Bi-group; n=18) or unipolar plus
      bipolar recording (Uni-group; n=18). In the Uni-group, the primary parameter used
      to select ablation sites was a QS or rS morphology of the His bundle unipolar
      recording. There was no significant difference between the 2 groups for the
      bipolar electrogram characteristics at the successful ablation site. However, in
      the Uni-group, the procedure time and fluoroscopy duration were shorter (both
      p<0.05), and the total number of RF energy applications less (p<0.05) than in the
      Bi-group. In the Uni-group, unipolar His bundle recordings could be assessed in
      26 (76%) of 34 RF energy applications: Complete atrioventricular block was
      obtained at 15 (83%) of 18 sites with QS morphology and in 3 (37%) of 8 sites
      with rS morphology on the unipolar His bundle recording. CONCLUSIONS: AVJ
      ablation can be achieved more efficiently and with fewer RF energy applications
      when guided by unipolar recordings than by bipolar recordings alone.

PMID- 17526984
TI  - The effect of diabetes mellitus on the P-wave dispersion.
AB  - BACKGROUND: P-wave dispersion (PD), a measure of heterogeneity of atrial
      refractoriness, is defined as the difference between the minimum (P min) and
      maximum P-wave (P max) durations on standard 12-lead electrocardiography (ECG).
      Increase in PD shows the intra-atrial and inter-atrial non-uniform conduction. In
      the present study the evaluation of the effect of diabetes mellitus (DM) on PD in
      patients without coronary artery disease and hypertension was carried out.
      METHODS AND RESULTS: Seventy-six diabetic patients who had no coronary artery
      disease or hypertension (group 1; mean age 48+/-9) and 40 healthy volunteer
      individuals (group 2; mean age 46+/-13) were enrolled in the study. After
      obtaining 12-lead surface ECG of all cases, P max and P min P-wave durations were
      measured and the differences between them were taken as PD (PD=P max-P min). Left
      atrium diameter, left ventricular end systolic and end diastolic diameters were
      measured and left ventricular ejection fraction was determined by
      echocardiography. Pulse wave mitral flow velocities were measured from the apical
      4-chamber view. Mitral early diastolic velocity (E), late diastolic velocity (A),
      E/A, E deceleration time and isovolumetric relaxation time were determined. In
      comparison of the 2 groups there was no statistically significant difference
      among age, sex, systolic and diastolic blood pressure, resting heart rate and
      body mass index of the cases. Although PD and P max were significantly higher in
      diabetic patients, there was no difference between P min values (33+/-12 vs 28+/
      10, p=0.02; 99+/-12 vs 93+/-10, p=0.011; 66+/-9 vs 65+/-10, p=NS; respectively).
      CONCLUSIONS: DM might increase PD even without ischemia, hypertension and left
      ventricular hypertrophy.

PMID- 17526985
TI  - Difference in myocardial flow reserve between patients with dilated
      cardiomyopathy and those with dilated phase of hypertrophic cardiomyopathy:
      evaluation by 15O-water PET.
AB  - BACKGROUND: The clinical features of patients with the dilated phase of
      hypertrophic cardiomyopathy (DHCM) may resemble those of patients with dilated
      cardiomyopathy (DCM); that is, systolic dysfunction and left ventricular
      dilatation. Myocardial flow reserve (MFR) is impaired in patients with
      nonischemic cardiomyopathy, and the reduced MFR may be related to poor prognosis.
      Several studies report that the mortality rate for patients with DHCM is higher
      than for DCM, but the difference between these 2 cardiomyopathies is still
      unclear. The purpose of this study was to assess the MFR of these 2
      cardiomyopathies, using (15)O-water positron emission tomography (PET) to
      elucidate their differences. METHODS AND RESULTS: In total 30 patients were
      investigated: 23 with DCM (Group A) and 7 with DHCM (Group B). All those who were
      in a stable condition underwent cardiac catheterization. Myocardial blood flow
      (MBF) at rest and under ATP infusion was measured by (15)O-water PET, and the MFR
      was calculated. There were no significant differences in the hemodynamics of the
      2 groups. The mean MFR in DHCM was significantly lower than that in DCM (1.49+/
      0.31 vs 2.62+/-1.08; p=0.042), whereas MBF at rest did not differ (DCM vs DHCM:
      0.66+/-0.20 vs 0.49+/-0.05 ml . min(-1) . g(-1); NS). The MFR in both Group A and
      B was significantly decreased compared with the normal controls (MFR in normal
      controls: 5.15+/-1.64, p=0.00015, 0.00013, respectively). CONCLUSIONS: These
      results suggest that impaired vasodilatation (ie, dysfunction of the
      microcirculation) is more severe in patients with DHCM than in patients with DCM,
      even though patients' characteristics and hemodynamics do not differ.

PMID- 17526986
TI  - Role of transthoracic Doppler-determined coronary flow reserve in patients with
      chest pain.
AB  - BACKGROUND: The assessment of patients with chest pain is an important step to
      make a diagnosis and clinical decision. Coronary flow reserve (CFR) can be used
      for the screening of significant coronary stenosis. However, the feasibility and
      limitation of CFR in those patients remains unknown. METHODS AND RESULTS: A total
      of 100 patients with chest pain were examined. CFR was measured in all 3 major
      coronary arteries by using transthoracic Doppler echocardiography (TTDE).
      Coronary angiography was performed 1 to 3 days after TTDE. CFR in all 3 major
      coronary arteries could be measured in 83 (83%) of 100 patients. The echo
      contrast agent was useful in 32 of 49 patients who had unclear color Doppler
      images. When CFR <2.0 was regarded as the cut-off point, the overall agreement
      rate between CFR and the results of coronary angiography was 83% (69 of the 83
      patients). In addition, CFR could predict the presence of coronary artery disease
      satisfactorily (sensitivity 85%, specificity 81%, positive predictive value 89%,
      negative predictive value 93%). CONCLUSIONS: TTDE seems to be a promising tool
      for screening patients with chest pain. Moreover, an echo-contrast agent seems to
      be an effective and supportive tool for patients who have poor visualization of
      coronary flow.

PMID- 17526987
TI  - Clinical significance of tissue Doppler imaging in patients with hypertrophic
      cardiomyopathy.
AB  - BACKGROUND: A transmitral E/septal Ea ratio > or =15 is a predictor of adverse
      outcome in cardiac disease, so it was hypothesized that a septal E/Ea >/=15 would
      predict the risk of adverse outcome, including sustained ventricular tachycardia
      (VT), cardiac arrest, implantable cardioverter defibrillator (ICD) discharge, or
      sudden death (SD) in patients with hypertrophic cardiomyopathy (HCM). METHODS AND
      RESULTS: The study group comprised 96 consecutive patients with HCM (median age
      53 years) who completed all noninvasive tests for risk stratification. The
      endpoint of the study was defined as death, cardiac arrest, documented sustained
      VT, or ICD-discharge. The median follow-up was 20.6 months. All patients were
      alive at the end of follow-up, although 8 patients had reached the endpoint
      during the study period. The variables that were predictive of adverse clinical
      outcome were family history of premature SD (p=0.03), syncope (p<0.001), maximum
      wall thickness > or =3 cm (p=0.02), and septal E/Ea > or =15 (p<0.001). In a
      stepwise multivariable model the only independent prognostic indicator was a
      septal E/Ea > or =15 (relative risk 0.26, 95% confidence interval 0.2-0.58,
      p<0.001). The cumulative event-free survival rate was 78.9% in patients with
      septal E/Ea > or =15, and 100% in patients with septal E/Ea <15 (p=0.0003).
      CONCLUSIONS: Septal E/Ea > or =15 predicts patients with HCM who are at risk of
      sustained VT, cardiac arrest, ICD-discharge, or SD. (Circ J 2007; 71: 897 - 903).

PMID- 17526988
TI  - Safety of and tolerance to adenosine infusion for myocardial perfusion single
      photon emission computed tomography in a Japanese population.
AB  - BACKGROUND: Adenosine has been available for use in myocardial perfusion single
      photon emission computed tomography (SPECT) in Japan since 2005. The purpose of
      this study was to evaluate the safety of and tolerance to thallium-201 myocardial
      perfusion SPECT with intravenous adenosine infusion in Japanese patients with
      suspected coronary artery disease. METHODS AND RESULTS: Two hundred and six
      consecutive patients who underwent an adenosine infusion (120 mug . kg(-1) . min(
      1)) SPECT at Sumitomo Besshi Hospital (Niihama, Japan) were investigated. The
      effects of adenosine infusion were monitored for each patient. A coronary
      angiography was performed in 81 patients. Adenosine infusion significantly
      decreased blood pressure and increased heart rate. Adverse reactions were
      observed in 161 patients (78.2%). Most reactions were transient, disappearing
      soon after the termination of adenosine infusion. No serious adverse reactions,
      such as acute myocardial infarction or death, occurred. Adenosine infusion was
      terminated in 3 patients (1.5%) because of near syncope or sustained 2:1
      atrioventricular block. Electrocardiographic changes occurred in 15 patients
      (7.3%). Self-assessed scoring after SPECT showed that the patients were very
      tolerant (74.6% of 177 patients) of adenosine infusion myocardial SPECT. The
      sensitivity and specificity were 75.0% and 69.7%, respectively. CONCLUSIONS:
      Adenosine infusion myocardial SPECT is safe and well tolerated in the Japanese
      population, despite the frequent occurrence of minor adverse reactions.

PMID- 17526989
TI  - Accuracy of nonstenotic coronary atherosclerosis assessment by multi-detector
      computed tomography.
AB  - BACKGROUND: The ability to evaluate coronary stenosis using multi-detector
      computed tomography (MDCT) has been well discussed. In contrast, several studies
      demonstrated that the plaque burden measured by intravascular ultrasound (IVUS)
      has a relationship to the risk of cardiovascular events. the accuracy of MDCT was
      studied to determine plaque and vessel size compared with IVUS. METHODS AND
      RESULTS: Fifty-six proximal lesions (American College of Cardiology/American
      Heart Association classification: segment 1, 5, 6) from 33 patients were assessed
      using MDCT and IVUS. The plaque and vessel area were measured from the cross
      sectional image using both MDCT and IVUS. Eight coronary artery lesions with
      motion artifacts and heavily calcified plaques were excluded from the analysis.
      The vessel and lumen size evaluated using MDCT were closely correlated with those
      evaluated by IVUS (R(2)=0.614, 0.750 respectively). Furthermore, there was a
      strong correlation between percentage plaque area assessed by MDCT and IVUS
      (R(2)=0.824). CONCLUSION: MDCT can noninvasively quantify coronary
      atherosclerotic plaque with good correlation compared with IVUS in patients with
      atherosclerosis.

PMID- 17526991
TI  - Vasoconstrictive response in the vascular beds of the non-exercising forearm
      during leg exercise in patients with mild chronic heart failure.
AB  - BACKGROUND: Reduced exercise capacity may be related to decreased redistribution
      of blood flow from the non-exercising tissues to the exercising skeletal muscle
      in patients with mild chronic heart failure (CHF). METHODS AND RESULTS: In the
      present study 14 patients with mild CHF and 10 healthy subjects (N) underwent
      symptom-limited multistage-ergometer exercise, during which forearm vascular
      resistance (FVR), cardiac index (CI), systemic vascular resistance index (SVRI),
      and oxygen uptake (VO(2)) were measured non-invasively using the plethysmograph,
      impedance, and respiratory gas analysis methods, respectively. The VO(2) and CI
      at peak exercise were lower (p<0.01 each), and SVRI and FVR at both rest and peak
      exercise were higher in the CHF group than in N. However, both the percent
      increase in FVR and percent decrease in SVRI from the resting state to peak
      exercise were lower in CHF than N, and both of them correlated with not only peak
      VO(2), but also the corresponding resting value of FVR and SVRI (p<0.01 each).
      CONCLUSIONS: Redistribution of blood flow from the non-exercising tissues to the
      working skeletal muscles, which may participate in exercise capacity, can be
      blunted in CHF. The decreased vasoconstrictive response in the non-exercising
      tissues is intimately related to the increased resting vascular tone in CHF.

PMID- 17526990
TI  - Comparison of active renin concentration and plasma renin activity as a
      prognostic predictor in patients with heart failure.
AB  - BACKGROUND: Plasma renin activity (PRA) may be limited to angiotensinogen levels,
      which decrease in patients with heart failure (HF) because of liver congestion.
      METHODS AND RESULTS: To evaluate whether the plasma active renin concentration
      (ARC) is a more useful prognostic predictor than PRA, the plasma levels of ARC,
      PRA, angiotensin II, aldosterone, brain natriuretic peptide (BNP),
      norepinephrine, and hemodynamic parameters were measured in 214 consecutive HF
      patients who were already taking angiotensin-converting enzyme inhibitors (ACEI)
      or angiotensin-receptor blockers (ARB). Median follow-up period was 1,197 days.
      Of the clinical variables, including pulmonary capillary wedge pressure, right
      atrial pressure, left ventricular ejection fraction, and neurohumoral factors,
      only high plasma levels of log ARC (p<0.0001) and log BNP (p=0.0009), but not log
      PRA, were significant independent prognostic predictors. Log ARC/PRA ratio was
      significantly higher in nonsurvivors than in survivors. Log ARC/PRA significantly
      correlated with pulmonary capillary wedge pressure (r=0.305, p<0.0001), right
      atrial pressure (r=0.222, p=0.0011), and log BNP (r=0.242, p=0.0004).
      CONCLUSIONS: Plasma ARC is superior to PRA and a high plasma ARC is an
      independent prognostic predictor in HF patients who are already receiving ACEI or
      ARB.

PMID- 17526992
TI  - Serum carboxy-terminal telopeptide of type I collagen (ICTP) predicts cardiac
      events in chronic heart failure patients with preserved left ventricular systolic
      function.
AB  - BACKGROUND: Clinical markers to predict adverse outcome have not yet been
      established for patients with preserved left ventricular (LV) systolic function.
      The present study was designed to examine whether carboxy-terminal telopeptide of
      type I collagen (ICTP), a marker of collagen degradation, is useful for
      determining the prognosis of such patients. METHODS AND RESULTS: Serum levels of
      ICTP were measured at admission in 156 consecutive patients hospitalized for
      chronic heart failure (CHF). Patients were divided into 2 groups based on the LV
      ejection fraction (LVEF): reduced LV systolic function group (LVEF <50%, n=92)
      and preserved LV systolic function group (LVEF > or =50%, n=64). In preserved LV
      systolic function group, cardiac event-free rates were significantly lower in
      high ICTP group than in low ICTP group (p<0.001). The area under the receiver
      operating characteristic curve of ICTP in the preserved LV systolic function
      group was markedly larger than that in the reduced LV systolic function group.
      Cox multivariate analysis also revealed that ICTP was an independent predictor of
      cardiac events in the preserved LV systolic function group. CONCLUSION: Serum
      ICTP level is highly reliable for risk stratifying CHF patients with preserved LV
      systolic function.

PMID- 17526993
TI  - Characteristics of congestive heart failure accompanied by atrial fibrillation
      with special reference to tachycardia-induced cardiomyopathy.
AB  - BACKGROUND: Sustained tachycardia causes left ventricular (LV) systolic
      dysfunction leading to heart failure (HF), which is widely known as "tachycardia
      induced cardiomyopathy (TIC)", but its prevalence and prognosis in Japanese
      remain unclear. METHODS AND RESULTS: Of 213 consecutive patients with HF
      associated with atrial fibrillation (AF) requiring hospitalization (n=213)
      between January 1999 and December 2004, and 104 (83 males, 67+/-12.6 years) were
      identified as not having any structural heart disease. Of them 41 (39%) had a
      normal LV ejection fraction (LVEF) at the initial admission, and the remaining
      patients fell into 2 groups: those with rapid (<6 months) normalization of the
      LVEF after AF management (presumed TIC, 30 patients, 29%) and those with
      persistent LV systolic dysfunction (dilated cardiomyopathy (DCM), 33 patients,
      32%). Although the B-type natriuretic peptide value and LVEF did not differ
      between the 2 groups, the LV size on admission was significantly smaller in the
      TIC group (LV end-diastolic dimension (LVDd) 57.6+/-7.2, LV end-systolic
      dimension (LVDs) 49.4+/-8.0) than in the DCM group (LVDd 63.4 +/-8.8, LVDs 55.3+/
      9.6, p<0.05). During a follow-up period of 42.1+/-21.2 months, cardiac death and
      recurrent HF hospitalization were significantly less frequent in the TIC group
      than in the DCM group. CONCLUSIONS: In AF-associated HF requiring
      hospitalization, TIC is the presumed cause in approximately one-third of patients
      without any previously known structural heart disease. That particular group is
      characterized by a relatively smaller LV and better prognosis under medical
      treatment.

PMID- 17526994
TI  - Significance of peritoneal fluid drainage in management after repair of complex
      heart defects in infancy: cytokine dynamics in vivo.
AB  - BACKGROUND: In vivo redundancy of pro-inflammatory cytokines results in a vicious
      cycle of systemic inflammatory response syndrome and low cardiac output syndrome
      (LOS). The purpose of this study was to elucidate the influence of peritoneal
      fluid (PF) drainage on cytokine dynamics in vivo and the significance of early
      induction for infants with LOS. METHODS AND RESULTS: Seven infants, who underwent
      early PF drainage to manage LOS after repair of complex heart defects under
      cardiopulmonary bypass, were enrolled. The serum and PF levels of the pro- and
      antiinflammatory cytokines, interleukin (IL)-6, -8, -10 and tumor necrosis factor
      (TNF)-alpha, were measured during the perioperative period. Clinical outcomes
      were observed simultaneously. There were no cases of early or late death, or
      infectious complications. Drainage volume of PF peaked just after operation, and
      decreased completely. The amount of proinflammatory cytokines in the PF increased
      for 3 days after operation. Of the proinflammatory cytokines in the PF IL-6
      increased the earliest and cleared the fastest. The amount of cleared IL-8 and
      TNF-alpha peaked on the 3rd postoperative day and resembled the course of C
      reactive protein (CRP). Serum levels of CRP and proinflammatory cytokines in
      patients with PF drainage decreased significantly more than those without PF
      drainage. CONCLUSIONS: Early initiation of PF drainage is useful in the
      postoperative critical care of infants with LOS by improving cytokine dynamics in
      vivo, although there are differences between the severity of patients undergoing
      PF drainage and those who do not.

PMID- 17526995
TI  - Increased thrombogenesity in patients with cyanotic congenital heart disease.
AB  - BACKGROUND: The basic mechanisms of thromboembolism in cyanotic congenital heart
      disease (CCHD) have not been well clarified. P-selectin on the platelets reflects
      platelet activation. Thrombomodulin is a critical cofactor for thrombin-mediated
      activation of protein C and reflects the anticoagulant activity of the
      endothelium. The present study was performed to evaluate whether platelet
      activation exists in patients with CCHD. METHODS AND RESULTS: Platelet P-selectin
      as a marker of platelet activation, plasma thrombomodulin level and protein C
      activity as markers of anticoagulant activity of the endothelium and thrombin -
      antithrombin complex III (TAT) were examined in 35 patients with CCHD. Plasma
      thrombomodulin level (1.1+/-0.9 vs 2.2+/-0.3 FU/ml) and protein C activity
      (71.1+/-29.8 vs 117.8+/-24.8%) were significantly lower in patients with CCHD as
      compared with the control subjects. The levels of plasma TAT (255+/-811 vs 1.9+/
      0.9 ng/ml) and P-selectin on platelets (6.3 +/-4.5 vs 3.3+/-0.3 mean fluorescence
      intensity) were significantly higher in the patients with CCHD than in the
      controls. Four of the CCHD patients who experienced thromboembolic events had
      elevated levels of platelet P-selectin (p=0.02) compared with CCHD patients
      without thromboembolic events. CONCLUSION: Platelet activation exists in patients
      with CCHD and it may play an important role in the thromboembolic events in CCHD.

PMID- 17526996
TI  - Difference in early effects of statin therapy on coronary and forearm flow
      reserve in postmenopausal hypercholesterolemic women.
AB  - BACKGROUND: The relationships between flow reserves in coronary and peripheral
      circulation and their modification by statin therapy have not been assessed in
      the same patients, especially females. METHODS AND RESULTS: To assess the effect
      of pravastatin on both circulation, in 20 postmenopausal female patients with
      hypercholesterolemia but a low probability of coronary artery disease, the
      forearm blood flow reserve (FBFR) using the plethysmographic method and coronary
      flow velocity reserve (CFVR) by Doppler echocardiography were measured before, 4
      and 8 weeks after starting the pravastatin and/or diet therapy. At baseline, CFVR
      and FBFR had a positive linear correlation (r=0.63, p<0.01) while each of them
      had a negative linear correlation (r=-0.53 to -0.63, p<0.05 each) with total or
      LDL-cholesterol levels. Four weeks after starting the pravastatin therapy when
      the decrease in total cholesterol reached a plateau, FBFR increased (p<0.05) by
      38+/-14%, whereas CFVR did not. Such an increase in FBFR by pravastatin was
      related to the degree of total or LDL-cholesterol lowering. CONCLUSIONS: In
      postmenopausal hypercholesterolemic women with a low probability of coronary
      artery disease, the cholesterol-lowering with pravastatin improved FBFR as early
      as 4 to 8 weeks after starting the therapy, whereas its effect on CFVR was
      unclear at that time.

PMID- 17526997
TI  - Pro-atherogenic alterations in T-lymphocyte subpopulations related to acute
      hyperglycaemia in type 2 diabetic patients.
AB  - BACKGROUND: T cells are among the earliest cells to infiltrate the arterial
      intima during the initial stages of atherosclerosis. Alterations in the
      peripheral blood lymphocyte distribution might be associated with intensive
      lymphocytes extravasation and stimulation of atherosclerotic plaque development.
      Epidemiological data reveal that short-term postprandial hyperglycemia is a
      significant risk factor for coronary heart disease. Using a parameter that
      indicates recently-past acute hyperglycemia, 1,5-anhydro-D-glucitol (1,5-AG), the
      aim of the present study was to elucidate which alterations in peripheral blood T
      lymphocytes, if any, are associated with acute hyperglycemia in patients with
      type 2 diabetes mellitus (DM) and, thus, might be involved in the progression of
      atherosclerosis. METHODS AND RESULTS: Measurement of fasting glucose level,
      glycated hemoglobin A(1c), 1,5-AG, lipid profile and lymphocyte receptors
      expression (CD3+, CD4+, CD8+, CD8+28+, CD+28 -) was performed in 97 patients with
      type 2 DM, 23 patients with coronary heart disease, and 15 healthy controls. The
      mean CD3+, CD4+, CD8+28 - and CD8+28+ lymphocyte counts were significantly higher
      in the DM patients than in both control groups. Multiple regression analysis
      revealed that CD4+ and CD8+28- lymphocyte counts primarily were dependent on 1,5
      anhydro-D-glucitol plasma levels. CONCLUSIONS: These results suggest that acute
      hyperglycemia results in the progression of atherosclerosis in type 2 DM, at
      least in part through changes in CD4+ and CD8+28- lymphocyte subsets.

PMID- 17526998
TI  - Correlation between body mass index and leucopenia after administration of
      valganciclovir for cytomegalovirus infection in chinese cardiac recipients.
AB  - BACKGROUND: Valganciclovir (VGC) has recently been proved efficacious for the
      prophylaxis and treatment of cytomegalovirus (CMV) infection in transplant
      recipients. Leucopenia is a troublesome complication of VGC but the possible risk
      factors are unknown. METHODS AND RESULTS: Once a cardiac recipient's quantitative
      real-time CMV-polymerase chain reaction result showed positive, VGC was
      administered for 3 months. The 61 cardiac recipients enrolled in this study were
      divided into 2 groups: non-leucopenia group (n=29) and leucopenia group (n=32).
      The white blood cell (WBC) counts in the leucopenia group dropped approximately
      55.6% in the first month after VGC therapy (pre-VGC WBC count: 5,544 cells/mm(3)
      vs post-VGC WBC count: 2,460 cells/mm(3), p<0.0001). The most significant
      difference between the 2 groups was body mass index (BMI, 23.04 vs 25.84,
      p=0.008), which was the impact factor of VGC-induced leucopenia. CONCLUSION:
      Severe leucopenia may develop after VGC therapy in Chinese cardiac recipients,
      especially those with lower BMI.

PMID- 17526999
TI  - Beta-, not alpha-adrenergic stimulation enhances conduction velocity in cultures
      of neonatal cardiomyocytes.
AB  - BACKGROUND: During both cardiac maturation and myopathy, elevated levels of
      circulating catecholamines coincide with alterations in impulse propagation. An
      in vitro model of cultured cardiomyocytes was used to study the effects of
      adrenergic stimulation on the conduction characteristics of immature heart cells.
      METHODS AND RESULTS: Neonatal rat cardiomyocytes were cultured on preparations
      designed to measure conduction velocity (CV). CV was measured on the same
      preparation twice at t=0 and at t=24 h. Under control conditions (n=7), CV at t=0
      (30.9+/-1.9 cm/s) and t=24 (32.4+/-4.4 cm/s) was similar (p=0.70).
      Immunohistochemistry revealed expression of the gap junction proteins connexin
      (Cx) 40, Cx43 and Cx45, with Cx43 being highly predominant. Stimulation for 24 h
      with the beta-adrenergic agonist isoproterenol (ISO) significantly increased CV
      from 28.0 +/-2.0 cm/s at t=0 to 34.8+/-2.2 cm/s at t=24 (p=0.002, n=5).
      Microelectrode recordings showed a faster upstroke of the action potential (AP)
      of ISO-treated cells. Reverse transcribed-polymerase chain reactions (RT-PCR)
      showed that ISO increased expression of SCN5A and alpha(1c) (alpha-subunit of the
      cardiac sodium and L-type calcium channel, respectively). Stimulation of cells
      with ISO did not induce alterations in distribution or expression of Cx40, Cx43
      and Cx45 (both mRNA and protein), but slightly increased the phosphorylation of
      Cx43. Stimulation for 24 h with the alpha-adrenergic agonist phenylephrine did
      neither affect CV nor the expression of the connexin isoforms, SCN5A and
      alpha(1c). CONCLUSIONS: Alpha- and beta-adrenergic stimulation differently affect
      propagation of the electric impulse, which is primarily not caused by a
      differential effect on intercellular coupling. RT-PCR analysis and an enhanced AP
      upstroke velocity indicate a higher functional expression level of alpha(1c) and
      SCN5A in beta-adrenergic stimulated cells, which may explain the observed
      increase in CV.

PMID- 17527000
TI  - Left ventricular apical rupture caused by takotsubo cardiomyopathy--comprehensive
      pathological heart investigation.
AB  - An 81-year-old woman with emotionally-induced takotsubo cardiomyopathy developed
      a fatal left ventricular (LV) apical rupture. During the hospitalization
      persistent ST-segment elevation with no electrocardiographic time evolution was
      observed on the ECG, characteristic for takotsubo cardiomyopathy.
      Histopathologically, transmural myocardial necrosis with hemorrhage was found at
      the rupture site, but there were foci of coagulation and contraction band
      necrosis with mononuclear lymphocyte infiltrations in other heart regions, and
      the intensity and distribution of these pathological changes corresponded to the
      distribution of the LV contraction abnormalities seen on ventriculography. The
      article concludes that: the LV functional disorder in takotsubo cardiomyopathy
      may be caused by distracted foci of coagulation and contraction band necrosis in
      the myocardium; contraction band necrosis (a sign of catecholamine
      cardiotoxicity) may reflect the sympathetic hyperactivity in this disease;
      persistent myocardial damage expressed by persistent ST-segment elevation without
      an electrocardiographic time evolution should be carefully observed with
      sequential echocardiographic examinations because of the possibility of cardiac
      rupture.

PMID- 17527001
TI  - Lipomatous hypertrophy of the interatrial septum with cutaneous lipomatosis.
AB  - A mass was identified in the atrial septum by clinical imaging in a patient who
      had multiple large lipomas of the skin. Multislice computed tomography and
      magnetic resonance imaging indicated that the interatrial mass was a fatty
      infiltration. In order to discriminate the myocardial lesion from myxoma and
      other benign conditions and malignant tumors, percutaneous transvenous biopsy was
      performed. Microscopic examination demonstrated the cardiac mass to be lipomatous
      hypertrophy of the interatrial septum (LHIS), and the skin lesions, simple
      lipomas. The LHIS is itself a rare condition, and its development in patients
      having multiple ponderous lipomas, or lipomatosis, could not be found in a
      previous report. This may be the first published case of LHIS, which likely
      represents cardiac involvement of lipomatosis.

PMID- 17527002
TI  - Guidelines for diagnosis of takotsubo (ampulla) cardiomyopathy.
AB  - BACKGROUND: It is important to differentiate takotsubo cardiomyopathy from other
      types of transient ventricular dysfunction. These guidelines, resulting from a
      workshop sponsored by the Ministry of Health, Labour, and Welfare, Idiopathic
      Cardiomyopathy Research Committee, outline the steps necessary for diagnosis of
      takotsubo cardiomyopathy. METHODS AND RESULTS: The survey was conducted by
      mailing a questionnaire to the researchers of the 203 institutions that had made
      presentations on this disease at scientific meetings of the Japanese Circulation
      Society from November 1989 to October 2002. The questionnaires were sent and
      collected on January 10, 2003. Based on the results of the questionnaire, the
      first edition of the guidelines for diagnosis of takotsubo cardiomyopathy was
      prepared and evaluated at the 2003 group meeting of the Research Committee. Out
      of 33 researchers in Japan who had published research papers on this disease, 21
      responded to the request and provided their opinions. The guidelines were revised
      and were approved at the 2004 group meeting. CONCLUSIONS: This summary provides
      standard guidelines for patients with takotsubo cardiomyopathy.

PMID- 17527003
TI  - A family of multiple endocrine neoplasia type 2A (MEN 2A) with Cys630Tyr RET
      germline mutation: report of a case.
AB  - Since the majority of multiple endocrine neoplasia type 2A (MEN 2A) patients have
      missense mutations at codon 634 and those with the Cys630 RET genotype mutations
      are extremely rare, limited clinical information is available about this rare
      type. We report here three members of one Japanese MEN 2A family with the
      Cys630Tyr genotype. A 67-year-old woman presented a firm thyroid nodule, and
      preoperative examination revealed medullary thyroid carcinoma with primary
      hyperparthyoidism and no pheochromocytoma. At surgery, bilateral medullary
      thyroid carcinomas and parathyroid adenoma were found. No lymph node metastasis
      was identified. Computed tomography scans and laboratory examination of blood
      have shown no evidence of tumor recurrence and no abnormality of parathyroid
      function during the 4 years after surgery. A 40-year-old man, the proband's son,
      was shown to have the same RET mutation, underwent total thyroidectomy
      prophylactically, and only microscopic foci of medullary thyroid carcinoma were
      found. A 10-year-old boy, the proband's grandson also having the same RET
      mutation, showed normal basal serum calcitonin level and has been followed up
      conservatively. To our knowledge, 18 patients of 6 families with the Cys630
      mutations have been reported so far. This is only the second reported case with
      primary hyperparathyroidism. RET 630 mutations might be associated with lower
      penetrance of primary hyperparthyoidism and pheochromocytoma.

PMID- 17527004
TI  - Effect of castration on extracellular matrix remodeling and angiogenesis of the
      prostate gland.
AB  - This study was conducted to evaluate the long term effect of castration on the
      prostate gland proliferation, extracellular matrix remodeling and angiogenesis.
      Prostate gland proliferation was assessed by immunolocalization of proliferating
      cell nuclear antigen (PCNA). The expression level of vascular endothelial growth
      factor (VEGF), transforming growth factor-beta (TGF-beta) and metaloprotenase-13
      (MMP-13) by the prostate gland were assessed by immunohistochemistry and
      quantitative real-time PCR. The expression of the above mentioned parameters by
      the prostate gland of mature intact dogs were compared to that of castrated dogs
      six months post-castration. The results showed that castration induced a
      remarkable atrophy of the prostate gland which was associated with a highly
      significant decrease in the PCNA proliferation index. Although TGF-beta protein
      was immunolocalized to the epithelial and stroma cells of the prostate gland from
      both intact and castrated dogs, castration induced a significant up-regulation of
      TGF-beta mRNA expression. VEGF mRNA expression and its encoded protein
      immunolocalization were decreased significantly by the prostate gland from
      castrated dogs as compared to that of intact dogs. Castration, on the other hand,
      resulted in no significant change in MMP-13 mRNA expression despite an effect on
      its cellular immunolocalization which appeared to be localized to the epithelial
      and stromal cells of the prostate gland from castrated dogs as compared to
      epithelial cells of the prostate gland from intact dogs. These results indicated
      that castration-induced prostate gland regression continued to exert a potent
      suppressive effect on prostate gland proliferation which might be mediated by the
      elevated level of TGF-beta. Moreover, the low expression level of VEGF might
      reflect a reduced blood flow demand by the regressed and growth-dormant prostate
      after castration.

PMID- 17527005
TI  - A novel missense mutation (P366T) of the LHX4 gene causes severe combined
      pituitary hormone deficiency with pituitary hypoplasia, ectopic posterior lobe
      and a poorly developed sella turcica.
AB  - LIM homeodomain transcription factors regulate many aspects of development in
      multicellular organisms. LHX4/Lhx4 is a protein that is essential for pituitary
      development and motor neuron specification in mammals. In human, a heterozygous
      splicing mutation of the LHX4 gene was reported in a family with combined
      pituitary hormone deficiencies (CPHD). In addition to CPHD, these patients were
      characterized by small sella turcica and chiari malformation. Here we report a
      Japanese patient with CPHD (GH, PRL, TSH, LH, FSH, and ACTH deficiency) due to a
      novel missense mutation (P366T) of the LHX 4 gene. She showed severe respiratory
      disease and hypoglycemia soon after birth. Brain MRI demonstrated hypoplastic
      anterior pituitary, ectopic posterior lobe, a poorly developed sella turcica, and
      chiari malformation. Sequence analysis of the LHX 4 gene identified a
      heterozygous missense mutation (P366T) in exon 6, which was present in LIM4
      specific domain. Neither of the patient's parents harbored this mutation,
      indicating de novo mutation.

PMID- 17527006
TI  - [Respiratory diseases in the elderly].

PMID- 17527007
TI  - [End-of-life care in the elderly patients--resolving ethical dilemmas in Japan].

PMID- 17527008
TI  - [Recent topics in the treatment of osteoporosis in Japan].

PMID- 17527009
TI  - [Metabolic syndrome and aging].

PMID- 17527010
TI  - [Epidemiology of life-style related diseases in the elderly].

PMID- 17527011
TI  - [Clinical characteristics and antihypertensive therapy in hypertension in the
      elderly].

PMID- 17527012
TI  - [Diabetes mellitus in the elderly].

PMID- 17527013
TI  - [Management of hyperlipidemia in the elderly].
AB  - Serum cholesterol and triglyceride elevate with age until middle generation, and
      decline in old age. This change is partly accounted for by the change of
      endogenous sex hormones, especially in women. The incidence of dyslipidemia is
      not different between people of middle age and old age. However, the treatment is
      not the same in the two age groups. This is based on the idea that the impact of
      hyperlipidemia declines with age. There are some reports in which the
      significance of treatment of hyperlipidemia was examined: statin treatment
      appears beneficial for young-old people, while treatment of hyperlipidemia
      appears no longer beneficial for old-old people. Prospective study is needed
      before understanding the necessity of the treatment of hyperlipidemia in the old
      old people.

PMID- 17527014
TI  - [Obesity].

PMID- 17527015
TI  - [Prevention of life-style related disease among the elderly--Implication and
      limitation].

PMID- 17527016
TI  - [Regulation of self-renewal of stem cells by aging-related genes].

PMID- 17527017
TI  - [The mechanism of vascular senescence regulated by longevity gene, Sirt1].

PMID- 17527018
TI  - [Impact of metabolic shift on cellular lifespan].

PMID- 17527019
TI  - [Treatment of intractable high blood pressure in elderly patients].

PMID- 17527020
TI  - [Treatment for elderly diabetic patients with poor diet-management].

PMID- 17527021
TI  - [Instruments for diagnosis and treatment of mild dementia].

PMID- 17527022
TI  - [Dietary habit and longevity].
AB  - Obesity is one of the most important causes of life-style related diseases, and
      recently its pathophysiology is emphasized as metabolic syndrome. Preventing
      obesity by good dietary habit is a key to achieve healthy longevity. However, a
      lean body is not always good for health. There is an ideal body size for each
      person. This ideal body size differs according to age. Especially in the elderly,
      to prevent weight loss is more important for maintaining health and longevity
      than to be obese. Malnutrition is a critical factor of diseases and death in the
      elderly. Problems in nutritional status, and dietary intake, and methods of
      nutritional assessment in the elderly are discussed. Ideal body size for health
      and longevity, the relationship of body fat distribution and intra-abdominal fat
      accumulation health, and the effects of rapid weight change are also discussed to
      clarify the association of dietary habit and nutrition with longevity.

PMID- 17527023
TI  - [Anthropometric measurements as a predictor of mortality of community-dwelling
      Japanese elderly: the Nagoya Longitudinal Study of Frail Elderly (NLS-FE)].
AB  - AIM: This study aimed to evaluate the relationship between anthropometric
      measurements and mortality among community-dwelling frail elderly. METHODS: This
      study was a prospective cohort analysis of 520 community-dwelling elderly
      registered in the Nagoya Longitudinal Study for Frail Elderly (NLS-FE). Data
      included the participants' demographic characteristics, body mass index (BMI),
      mid-arm circumference (MAC), triceps skinfold (TSF), and arm muscle area (AMA),
      basic activities of daily living, comorbidity. BMI and TSF values were
      categorized into three groups, respectively, according to above the 75th
      percentile, the 25-75th percentile, and below the 25th percentile of Japanese
      Anthropometric Reference Data (JARD 2001). Survival analysis of 21-month
      mortality was conducted using Kaplan-Meier curves and multivariate Cox
      proportional hazards models. RESULTS: BMI and TSF were independent risk factors
      for 21-month mortality in the study participants. Significant higher risk of 21
      month mortality was observed in participants below the 75th percentile of BMI or
      below the 25th percentile of TSF set in JARD 2001. A striking increase in the
      risk of 21-month mortality, adjusting for potential confounding factors, was
      observed in the below 75th percentile of the BMI group with a below 25th
      percentile TSF of JARD 2001, compared with the 75th or above percentile BMI group
      with the 25th or above percentile TSF. CONCLUSION: The combination of BMI and TSF
      is a predictor of 21-month mortality among older people with ADL dysfunction.

PMID- 17527024
TI  - [Clinical features and prognosis of terminally ill patients in a geriatric long
      term care hospital with particular regard to the implications of artificial
      nutrition].
AB  - AIM: To clarify the clinical features of terminally ill patients in our hospital
      and elucidate the implications of administering artificial nutrition. METHODS:
      Between April 2004 and March 2005, we assessed 155 patients who died in
      Nishimaruyama Hospital--a geriatric long-term care facility in Sapporo. We
      analyzed their clinical backgrounds on admission, the clinical course up to the
      terminal stage of the illness, and the outcome of patients who received
      artificial nutrition. RESULTS: In 95 patients, the main cause of the terminal
      illness was infection. The symptoms of these patients, such as cerebral
      infarction and cognitive dysfunction, deteriorated progressively, and eventually,
      eating became difficult. At this point, alternative methods for providing
      nutrition were discussed. For 60 patients (41 died of acute disease and 19, of
      advanced cancers), artificial nutrition was not considered. Artificial nutrition
      was administered to 63 patients; tube feeding was carried out in 30 patients.
      Because of repeated aspiration pneumonia, 14 of these 30 patients eventually
      underwent intravenous hyperalimentation (IVH). Thirty-three patients directly
      underwent IVH. Thirty-two patients did not undergo any feeding course. The mean
      survival times of the tube feeding and non-artificial nutrition groups were 827
      and 60 days, respectively. The difference in the survival times was statistically
      significant. CONCLUSION: The outcome of patients who were placed on tube feeding
      was good. This may be because we selected those patients considered most suitable
      for tube feeding or IVH. The criteria that were used to select an appropriate
      method for providing nutrition varied, although the patients in our hospital
      requested palliative care.

PMID- 17527025
TI  - [Health status of community-dwelling elderly with geriatric syndrome].
AB  - OBJECTIVES: This study was conducted in order to examine the prevalence of
      geriatric syndrome (falls, incontinence, depression, and under-nutrition) in
      community-dwelling elderly people, and to analyze the health status of the
      elderly with geriatric syndrome risk compared to those of a group not at risk.
      METHODS: The subjects comprised 1,784 residents (769 men and 1,015 women) aged 70
      years or more living in Itabashi-ku, Tokyo, who took part in the study. For this
      study, we divided the subjects into two groups: those with geriatric syndrome
      (n=688) and those without (n=1,096). RESULTS: It was found that 33.6% of men and
      42.4% of women had geriatric syndrome. Elderly with geriatric syndrome in both
      men and women had a significantly lower the proportion of subjects who perceived
      as 'healthy' in terms of the self-rated health, the higher-level functional
      capacity, higher prevalence of fear of falling, and decreased physical
      performance including handgrip strength and usual.maximal walking speed than
      those in the group who did not have geriatric syndrome. Logistic regression
      analysis showed that geriatric syndrome was associated with poor perceived self
      rated health, a lower hemoglobin level and a slower usual walking speed in men,
      whereas in women it was associated with poor perceived self-rated health and fear
      of falling. CONCLUSION: Elderly individuals with geriatric syndrome have
      significantly decreased health status and physical performance compared to those
      without geriatric syndrome.

PMID- 17527026
TI  - [Characteristics of geriatric syndrome-subjects who did not participate in
      proffered intervention trial].
AB  - BACKGROUND: The present study was conducted to identify the characteristics of
      non-participants in intervention for geriatric syndrome among community-dwelling
      elderly. METHODS: The subjects were 208 men and 399 women aged 70 years and over
      who were eligible for participation in intervention programs for geriatric
      syndrome (falls, urinary incontinence, depression, and malnutrition) after
      recruitment based on a baseline health examination survey in 2002. Multiple
      logistic regression analysis was performed to assess non-participation in the
      intervention program as a dependent variable, and the relevant characteristics
      for participation in the baseline survey as the independent variables. RESULTS:
      The rates of participation in the intervention were 16.8% for men and 32.6% for
      women. Logistic regression analysis showed that male non-participants had not
      participated in group social activity (odds ratio (OR)=2.46, 95% confidence
      interval (CI) 1.08-5.59), and had no medical history of heart disease (OR=0.38,
      95%CI 0.17-0.89), whereas female non-participants had not lived alone (OR=0.53,
      95%CI 0.34-0.83), and had no medical history of hyperlipemia (OR=0.54, 95% CI
      0.34-0.84). CONCLUSION: Social activity, living arrangement, and medical history
      are related to non-participation in intervention for geriatric syndrome. It is
      necessary to devise various intervention programs and approaches to encourage
      participation.

PMID- 17527027
TI  - [Predictors of houseboundedness among elderly persons living autonomously in a
      rural community].
AB  - AIM: The housebound state is a risk factor for disability. This prospective study
      aimed to determine factors predictive of houseboundedness in the elderly, with an
      ultimate goal of preventing this condition. METHODS: A self-report questionnaire
      pertaining to mental, physical and social status was administered to 732
      community-dwelling elderly persons (313 men, 419 women; age range, 65-85 years)
      in October 2000. All subjects independently performed both basic and instrumental
      activities of daily living, went out alone for long distances, and did not use
      long-term care insurance. They were followed up until March 2003. "Housebound"
      was defined as leaving the house once a week or less. A stepwise multiple
      logistic regression model, adjusted for age, was used to identity factors
      predictive of houseboundedness. Data were analyzed on the basis of gender.
      RESULTS: By the end of the follow-up period, 14.4% of men and 26.0% of women had
      become housebound. Stepwise multiple logistic regression analysis showed that
      predictive factors for men were lack of frequent contact with friends, neighbors
      and relatives; symptoms of lower limb pain; and self-assessed weight or muscle
      loss; and predictive factors for women were lack of frequent contact with
      friends, neighbors and relatives; lower limb pain; and self-assessed
      deterioration in health. Limited social contact and the presence of lower limb
      pain were common predictive factors for houseboundedness in both men and women.
      CONCLUSION: The findings from this study show that, among autonomous elderly
      persons, those who are socially isolated or who have physical pain are more
      likely to become housebound.

PMID- 17527028
TI  - [Effect of end-of-life care teaching on the attitude of medical students to
      death].
AB  - AIM: We conducted a national survey to examine how programs to teach end-of-life
      care to medical students in Japanese medical schools influence their death
      attitude. METHODS: Sixteen medical schools participated. We conducted a
      questionnaire survey on fifth- or sixth-year medical students' death attitude at
      each medical school. Attitude of death was analyzed by the Death Attitude
      Inventory formed by Hirai et al, which is composed of seven factors: Afterlife
      belief, Death anxiety, Death relief, Death avoidance, Life purpose, Death
      concern, and Supernatural belief. We studied how students' attitude to death
      relates to programs to teach end-of-life care. RESULTS: Overall 1,017 of 1,510
      students (67.4%) from the 16 medical schools participated. The students who took
      a program to teach end-of-life care presented Afterlife belief, Death concern and
      Supernatural belief score higher than those who did not participate in any
      program. Multiple logistic regression analysis was conducted and it was found
      that those trend disappeared, and the students who took a program had greater
      Death anxiety significantly higher than those who took no program. CONCLUSION: We
      concluded that the attitude of medical students to death was not related to
      programs to teach end-of-life care in medical schools. Our survey suggested that
      improving end-of-life care education is needed to mold the attitude of medical
      students to death.

PMID- 17527029
TI  - [A case of Plummer disease that appeared in older old age after 10-year course of
      subclinical hyperthyroidism].
AB  - A 81-year-old woman with a thyroid tumor and subclinical hyperthyroidism since
      ten years ago was admitted to our hospital for palpitations and hyperthyroidism
      (FT(4) 1.75 ng/dl, FT(3) 5.37 pg/ml, TSH<0.03 microIU/ml). Although thyroid
      stimulating antibody (TSAb) was transiently and mildly positive, anti-TSH
      receptor antibody (TRAb), microsome test, and thyroid test were negative. Thyroid
      echogram showed an isoechoic nodule in the left lobe (33 x 42 x 22 mm) and a
      small nodule (10 x 15 x 9 mm) in right lobe. Thyroid scintiscan showed a
      hyperfunctional (hot) nodule in left thyroid lobe with suppressed uptake in the
      remainder of the gland. The uptake rate of thyroidal radioiodine ((123)I) in 24
      hours was within the normal range (7.3%). Based on the above findings, a
      diagnosis of Plummer disease was made. Since she refused invasive surgical or
      radioiodine treatment, she was treated with 10 mg thiamazole daily. After
      treatment with propranolol and thiamazole, the thyrotoxic symptoms disappeared
      and thyroid function returned to normal level. She had osteoporosis but she had
      neither atrial fibrillation nor cardiac symptoms. This was a rare case of Plummer
      disease that appeared in extremely old age after a long course of subclinical
      hyperthyroidism.

PMID- 17527030
TI  - [Reproducible efficacy of tricyclic antidepressant on chronic pain in an elderly
      patient with osteoporosis].
AB  - An 81-year-old woman was admitted due to exacerbation of chronic back pain from a
      vertebral osteoporosis fracture. The lumbar MRI examination revealed compression
      fracture of Th12 and L1 bones. Initial treatment with roxoprofen, calcitonin,
      bupurenorfin, and morphine did not achieve pain reduction in the patient. Because
      her geriatric depression scale score was low, we next tried to treat the pain
      using an antidepressant. Although the pain was improved by amitriptyline, the
      side effects of dry mouth and urinary incontinence were occurred. Milnacipran, a
      serotonin and norepinephrine reuptake inhibitor (SNRI), was then tried for the
      treatment of the chronic pain instead of amitriptyline, but the pain was
      increased. Then, she was given amitriptyline again for treatment of the chronic
      back pain instead of SNRI. The second-time amitriptyline treatment was effective
      to reduce the pain, with minimal side-effects. Because chronic pain due to
      osteoporosis is often difficult to treat in elderly patients, the classic
      antidepressant, amitriptyline, may help pain control by narcotics and anti
      inflammatory agents in some elderly patients.

PMID- 17527031
TI  - [An outbreak of noroviral gastroenteritis in a hospital].

PMID- 17527032
TI  - [Correlation between QOL utility score and VAS score of EuroQol in stroke
      patients].

PMID- 17527035
TI  - Effects of dietary iron reduction versus phlebotomy in patients with chronic
      hepatitis C: results from a randomized, controlled trial on 40 Japanese patients.
AB  - BACKGROUND AND AIM: Iron may play an important role in the pathogenesis of
      hepatitis C. We conducted this randomized, controlled trial comparing phlebotomy
      with dietary iron reduction. METHODS: Forty patients with chronic hepatitis C
      showing serum ferritin levels of over 150 ng/ml were randomized to either group A
      (low-iron diet for six months) or group B (phlebotomy biweekly). Phlebotomy was
      continued until serum ferritin had reached 20 ng/ml or less. RESULTS: At
      enrollment the clinical characteristics of patients in the two groups were
      similar. Serum ALT levels were significantly reduced in both groups, but the
      percent change in alanine aminotransferase (ALT) was larger in group B (median, 
      47.1 [range, -69.1 to -16.7] %) than in group A (-24.2 [-72.6 to 15.9] %,
      p<0.001). In group A subjects, no correlation was detected between percent change
      in ALT and clinical parameters. In group B subjects, the baseline ALT activity
      was significantly correlated with percent change in ALT (p<0.05), but iron
      related parameters were not correlated. CONCLUSION: The efficacy of phlebotomy is
      superior to that of dietary iron reduction in chronic hepatitis C. Serum levels
      of transaminase activities were a better indicator for phlebotomy than
      conventional indices of iron overload.

PMID- 17527036
TI  - Metabolic syndrome increases the risk of ischemic stroke in women.
AB  - BACKGROUND: Metabolic syndrome is a characterized by a cluster of cardiovascular
      risk factors, including visceral obesity, insulin resistance, dyslipidemia, and
      hypertension. The criteria for diagnosing metabolic syndrome differ among ethnic
      groups, due in part to differences in eating habits and body build. Little is
      known about the relationship between metabolic syndrome and ischemic stroke in
      Asian countries. The aim of this study was to investigate the relationship
      between metabolic syndrome and first-time ischemic strokes. SUBJECTS & METHODS:
      Study subjects were 1,493 Japanese adults aged 55 years-old or older with no
      diabetes mellitus, no history of stroke and no neurological abnormalities, who
      participated in a voluntary neurological health screening at the Institute of
      Shimane Health Science, Japan (767 men, 62.0 +/- 5.9 years old at entry and 726
      women, 61.8 +/- 5.1 years old at entry). All subjects were given an annual
      clinical stroke questionnaire. Clinical details of patients who reported strokes
      were confirmed with the attending physicians. Each subject was evaluated for an
      average of 6.4 +/- 3.8 years. Metabolic syndrome was defined using the modified
      criteria for Japanese population published in April 2005. RESULTS: Metabolic
      syndrome was diagnosed in 11.0% of men and 1.1% of women. Adjusting for age and
      smoking, female subjects with metabolic syndrome had a 23.1-fold increased risk
      of suffering ischemic strokes [95% confidence interval (CI), 2.7-196], whereas
      metabolic syndrome did not increase the risk of ischemic stroke in men.
      CONCLUSIONS: Metabolic syndrome is more likely to influence a risk for ischemic
      stroke in women than in men.

PMID- 17527037
TI  - Primary cardiac osteosarcoma in a young man with severe congestive heart failure.
AB  - A primary cardiac malignant tumor is very rare; its prevalence is only 0.002
      0.28%. Among most malignant tumors, angiosarcoma, leiomyosarcoma, and
      mesothelioma occupy the majority. A cardiac osteosarcoma is extremely rare: to
      our knowledge, only 36 cases have been reported worldwide. We present a 22-year
      old case featuring severe congestive heart failure. Hemodynamically the tumor led
      to significant obstruction of the mitral valve. The patient underwent an
      emergency resection operation, but multiple metastases occurred. Though the
      characteristics still remain unclear because of the low prevalence, it is very
      important that these tumors be distinguished from benign tumors because of early
      resection operation.

PMID- 17527038
TI  - SIADH is only an atypical clinical feature in a patient with prolactinoma.
AB  - A 50-year-old man was admitted to determine the pathogenesis of hyponatremia. He
      had a poor appetite and was easily fatigued. Physical findings showed that he was
      conscious and alert. He had neither dry skin or tongue, nor pretibial edema.
      Laboratory data revealed that the serum sodium level was 110 mmol/l; plasma
      osmolality, 238 mmol/kg; and urinary osmolality, 417 mmol/kg. Plasma arginine
      vasopressin was 0.5 pg/ml despite plasma osmolality of 242 mmol/kg. An acute
      water load showed impaired water excretion, as percent excretion of water load
      was 30% and minimal urinary osmolality was 642 mmol/kg. Serum prolactin was 254
      ng/ml, and anterior pituitary hormones of ACTH, TSH and GH were in the normal
      ranges. Brain magnetic resonance imaging (MRI) showed a pituitary tumor with a
      size of 20 x 22 x 21 mm and it pushed a pituitary stalk upward.
      Immunohistochemistry revealed prolactinoma. After the adenomectomy, serum sodium
      level has been kept normal with free access to water intake. The present study
      indicates that syndrome of inappropriate secretion of antidiuretic hormone
      (SIADH) is manifested in association with pituitary macroadenoma of prolactinoma.

PMID- 17527039
TI  - Renal intravascular large B-cell lymphoma localized only within peritubular
      capillaries. Report of a case.
AB  - We report a 35-year-old Japanese woman with intravascular large B-cell lymphoma
      diagnosed by percutaneous renal biopsy. The patient was referred to our
      institution for further examination of fever of unknown origin. She had renal
      dysfunction with a creatinine clearance of 44.1 mL/min, and daily urinary
      excretion of 0.22 g of protein and 21.5 mg of beta 2 microglobulin. Computed
      tomography showed markedly enlarged kidneys bilaterally. Percutaneous renal
      biopsy showed that an island-like atypical lymphoid cell accumulation was
      encircled with the peritubular capillary walls in many areas of the tubulo
      interstitium, resulting in marked destruction of tubular structure. However,
      almost all the glomeruli were intact. Immunohistochemical analysis confirmed the
      diagnosis of intravascular large B-cell lymphoma. Shortly after diagnosis, she
      was treated with rituximab, cyclophosphamide, hydroxydaunomycin, oncovin, and
      prednisolone, and her renal function and size improved. Renal involvement by
      lymphoma has been classified into two categories: intraglomerular intravascular
      lymphoma and tubulointerstitial diffuse invasion type that is distinct from
      intravascular lymphoma. For the latter cases with renal dysfunction and marked
      bilateral nephromegaly but without proteinuria, intravascular lymphoma within
      intra-peritublar capillaries should be considered as a possible diagnosis.

PMID- 17527040
TI  - Esophageal involvement in microscopic polyangiitis: a case report and review of
      literature.
AB  - A 72-year-old man with cough and sputum showed esophageal wall thickening and
      pneumonia in chest computed tomography (CT) scan. Following endoscopy, we
      diagnosed reflux esophagitis and subscribed proton pump inhibitor. The esophageal
      lesion, however, was intractable. We diagnosed microscopic polyangiitis (MPA)
      because of vasculitis symptoms, cytoplasmic antineutrophil cytoplasmic antibodies
      (cANCA) in blood and no granulomatous change in the esophagus. We adopted pulse
      therapy of cyclophosphamide and oral prednisolone; the symptoms and esophageal
      lesion were markedly improved. We concluded that the esophageal lesion was an
      aspect of MPA. To our knowledge, this is the first report of esophageal
      involvement in MPA.

PMID- 17527041
TI  - Interleukin-6-producing giant cell carcinoma of the lung with multicentric
      Castleman's disease-like presentation.
AB  - We encountered a 59-year-old man with advanced lung cancer with multiple swollen
      lymph nodes. At autopsy the lung cancer was revealed as giant cell carcinoma.
      Microscopic examination showed no cancer cells, but there was polyclonal
      proliferation of plasma cells in the lymph nodes and in the bone marrow. In the
      kidneys, proliferation of mesangial matrices and mesangial cells was found. This
      presentation resembled multicentric Castleman's disease (MCD), in which
      interleukin-6 (IL-6) has a great role. Immunohistochemical staining was positive
      for IL-6 in cancer cells. This is the first reported case of an IL-6-producing
      giant cell carcinoma of the lung with MCD-like presentation.

PMID- 17527042
TI  - Idiopathic hypereosinophilic syndrome presenting acute abdomen.
AB  - We describe a 27-year-old man with hypereosinophilc syndrome (HES) presenting
      acute abdomen due to acute thrombosis of the mesenteric artery, who had a past
      history of eosinophilic pneumonia followed by multiple arterial thromboses of the
      extremities. At the recurrence of eosinophilia, he was treated with high-dose
      corticosteroids. Immediately after the reduction of peripheral blood eosinophils,
      he suddenly developed perforation of the intestine due to acute thromboses of
      mesenteric arteries despite sustained anticoagulation therapy. Molecular analysis
      demonstrated that the FIP1L1-PDGFRA fusion gene was negative. Histopathology
      showed thrombi and eosinophilic inflammation of arteries. It is important to
      recognize that HES could be a cause of acute abdomen.

PMID- 17527043
TI  - Paradoxical cerebral embolism causing internal carotid artery occlusion.
AB  - Paradoxical cerebral embolism (PCE) is defined to be a pathological condition in
      which emboli originating from the venous system reach the cerebral arterial
      circulation via the right-to-left (R-L) shunt. In patients with PCE, emboli
      originating from the venous system most commonly pass through the patent foramen
      ovale during Valsalva-provoking activities which increase the right atrial
      pressure above the left atrial pressure. The size of cerebral infarction caused
      by PCE is generally small, since the size of emboli which can pass through the R
      L shunt is small. Here, we report a case of PCE which occluded the internal
      carotid artery (ICA).

PMID- 17527044
TI  - Do the effects of long-term lomerizine administration differ with age?

PMID- 17527045
TI  - Effect of edaravone, a free radical scavenger, on ischemic cerebral edema
      assessed by magnetic resonance imaging.
AB  - The anti-edema effect of edaravone, a free radical scavenger, was evaluated by
      magnetic resonance imaging in six patients with extensive hemispheric ischemic
      stroke. T(2) relaxation time in the infarct core, the boundary zone of the
      infarct, and the noninfarcted hemisphere were calculated, and T(2) mapping was
      performed before and after edaravone administration. Edaravone administration
      significantly decreased the mean T(2) relaxation time in the boundary zone of the
      infarct from 121.5 +/- 9.2 (mean +/- standard deviation) to 114.5 +/- 9.9 msec (p
      = 0.008), but not in the core from 142.3 +/- 13.4 to 142.2 +/- 18.5 msec (p =
      0.97) or the noninfarcted hemisphere from 93.0 +/- 3.7 to 93.1 +/- 3.8 msec (p =
      0.91). The T(2) subtraction map clearly demonstrated shortened T(2) relaxation
      time in the boundary zone of the infarct. The present results indicate that
      edaravone can salvage the boundary zone of the infarct and is a useful
      cytoprotective anti-edema agent.

PMID- 17527046
TI  - Single nucleotide polymorphism 309 affects murin-double-minute 2 protein
      expression but not glioma tumorigenesis.
AB  - Murin-double-minute 2 (MDM2) is an important negative regulator of the p53 tumor
      suppressor, and affects the p53 protein level and transcriptional activity. The
      genotype of the single nucleotide polymorphism in the promoter region of MDM2
      (single nucleotide polymorphism [SNP] 309) is associated with the MDM2 protein
      expression level and the onset age of several types of cancer. The SNP309
      genotype was investigated in 254 Japanese patients with glioma and 50 healthy
      subjects. The genotype frequency of SNP309 was T/T homozygous in 62 patients
      (24%), T/G heterozygous in 126 (50%), and G/G homozygous in 66 (26%) of the
      glioma patients, and was similar in the healthy subjects. The G/G ratio was
      higher in our Japanese subjects than in Western populations. Immunohistochemical
      study of glioma tissues showed that the G/G genotype was associated with higher
      expression of MDM2 protein compared to the T/T genotype, suggesting that SNP309
      attenuates MDM2 protein expression in vivo. However, no association was found
      between the SNP309 genotype and the histological grade of glioma, age at disease
      onset, or p53 gene mutation rate. In our study population, SNP309 affected MDM2
      protein level, but had no significant involvement in glioma tumorigenesis.

PMID- 17527047
TI  - Histological examination of false positive tissue resection using 5
      aminolevulinic acid-induced fluorescence guidance.
AB  - Intraoperative 5-aminolevulinic acid (5-ALA)-induced fluorescence guidance for
      resection of malignant brain tumors was correlated with histological examination
      to investigate false positive findings in 42 patients with malignant glioma and
      six patients with metastatic brain tumor. Patients received a single 1 g oral
      dose of 5-ALA 2 hours before surgery. The tumor site was illuminated with a laser
      with a peak wavelength of 405 +/- 1 nm and output of 40 mW. Samples with strong
      fluorescence were obtained from the tumor bulk and samples with weak fluorescence
      from the tumor cavity. Fluorescence was observed in 36 of the 42 malignant
      gliomas and four of the six metastatic brain tumors. No tumor cells were found in
      fluorescent samples from six of the 36 malignant gliomas and all four metastatic
      brain tumors. Five of the six malignant gliomas were recurrent cases.
      Fluorescence was found in areas of peritumoral edema or inflammatory cell and
      reactive astrocyte infiltration. Intraoperative 5-ALA-induced fluorescence
      guidance is useful for the resection of initial malignant glioma since false
      positive results are rare, but only non-eloquent weak positive areas should be
      resected. In contrast, all weak positive areas of recurrent malignant gliomas
      must be resected. Weak positive areas of the peritumoral edema surrounding
      metastatic brain tumors should be removed carefully as false positive results are
      common.

PMID- 17527048
TI  - Hemangioblastoma of the optic nerve--case report.
AB  - A 64-year-old man presented with a rare sporadic hemangioblastoma arising in the
      left optic nerve manifesting as left visual disturbance gradually progressive
      over 5 years. Magnetic resonance imaging revealed a well-enhanced mass in the
      left optic nerve. Partial resection of the tumor was performed via the
      frontoorbital approach. The histological diagnosis was optic nerve
      hemangioblastoma. Hemangioblastoma must be considered in the differential
      diagnosis of optic nerve tumors even in the absence of other lesions associated
      with von Hippel-Lindau disease.

PMID- 17527049
TI  - Total resection of a hemorrhagic tectal pilocytic astrocytoma--case report.
AB  - A 21-year-old man presented with a hemorrhagic pilocytic astrocytoma of the
      tectal plate manifesting as sudden onset of severe headache, vertigo, nausea, and
      vomiting. Computed tomography demonstrated acute hydrocephalus and hemorrhage
      within the brain stem and fourth ventricle. Magnetic resonance (MR) imaging
      revealed a dorsally exophytic tectal tumor as hypointense on the T(1)-weighted
      image and hyperintense on the T(2)-weighted image with contrast enhancement.
      Radical resection of the tumor was selected because of the unusual aggressive
      clinical course with hemorrhage and suspicion of malignant components. The tumor
      was totally resected via an occipital transtentorial approach using a
      neuronavigation system without surgical complications. The histological diagnosis
      was pilocytic astrocytoma. The patient was discharged home without neurological
      deficits on the 9th postoperative day. Twenty-three months after the surgery,
      follow-up MR imaging demonstrated no recurrence. Tectal plate pilocytic
      astrocytoma is rarely associated with hemorrhage but should be considered in the
      differential diagnosis of intracranial hemorrhage with acute presentation. Such
      exceptional tectal tumors should be resected radically and undergo histological
      examination to decide on further appropriate treatment.

PMID- 17527050
TI  - Symptomatic hemorrhage associated with recurrent pilocytic astrocytoma with
      granulation tissue--case report.
AB  - A 51-year-old woman had been followed up for 10 years for recurrence of pilocytic
      astrocytoma 5 years after the initial treatment consisting of subtotal resection,
      chemotherapy, and radiation therapy. The patient presented with sudden onset of
      headache and vomiting. Computed tomography and T(2)*-weighted magnetic resonance
      imaging revealed hemorrhage in the tumor located in the right basal ganglia,
      thalamus, and hypothalamus. She underwent gross total resection of the lesion.
      Histological examination confirmed recurrent pilocytic astrocytoma with
      organizing hematoma and granulation tissue. Although neither symptomatic
      hemorrhage nor late benign recurrence is common, careful long-term follow up is
      necessary for patients with pilocytic astrocytoma.

PMID- 17527051
TI  - Complete response to temozolomide treatment in an elderly patient with recurrent
      primary central nervous system lymphoma--case report.
AB  - An 80-year-old woman presented with primary central nervous system (CNS) lymphoma
      manifesting as progressive disorientation and loss of activity. She received
      three cycles of high-dose methotrexate. The tumor shrank after two cycles and her
      mental status improved, but she suffered tumor recurrence. The second-line
      treatment consisted of four cycles of rituximab but the tumor enlarged. She was
      then treated with three cycles of temozolomide. Magnetic resonance imaging
      revealed no evidence of disease. Her mental status and performance status
      improved, and she suffered no toxicity. She is able to pursue her daily life
      without recurrence after 16 cycles of temozolomide. Temozolomide may be effective
      against relapsed primary CNS lymphoma without causing neurotoxicity in the
      elderly.

PMID- 17527052
TI  - Hematomyelia caused by ruptured intramedullary spinal artery aneurysm associated
      with extramedullary spinal arteriovenous fistula--case report.
AB  - A 53-year-old woman presented with a ruptured intramedullary aneurysmal
      dilatation fed by the anterior spinal artery associated with an arteriovenous
      malformation located in the ventral cervical spinal cord. She developed
      tetraparesis and respiratory dysfunction. The neurological deterioration was
      caused by hematomyelia due to the ruptured aneurysmal dilatation and progression
      of edema in the upper cervical spinal cord due to venous hypertension associated
      with additional hematoma in the medulla oblongata. Endovascular embolization of
      both C-1 and C-2 radicular arteries was performed with Guglielmi detachable
      coils, but components fed by small branches such as the radiculo-pial artery were
      not obliterated. Surgery was performed for extirpation of the arteriovenous
      malformation and cervical intramedullary hematoma, and excision of the aneurysmal
      dilatation through a transcondylar approach combined with vertebral artery
      transposition. Postoperatively, she overcame several complications such as
      pneumonia and endocarditis, and had only moderate weakness of the right upper and
      lower limbs. This case indicates that surgical intervention for high cervical
      intramedullary lesion may be very effective.

PMID- 17527053
TI  - True intraspinal neurenteric cyst in the lumbosacral region--case report.
AB  - A 56-year-old man presented with a very rare true neurenteric cyst in the conus
      medullaris without evidence of vertebral or visceral anomaly manifesting as a 6
      month history of mild low back and bilateral inguinal pain. No motor weakness was
      found in the bilateral lower extremities. He had also suffered dysesthesia in the
      bilateral feet for several weeks before admission. Lumbar spine magnetic
      resonance (MR) imaging demonstrated a cystic intradural extramedullary mass at
      the L1-2 levels without enhancement after gadolinium injection. MR imaging,
      computed tomography, and radiography detected no vertebral anomaly. Lumbar
      laminectomy at the L1-2 levels was performed and the lesion was incompletely
      removed. Histological examination showed the cystic wall lined with ciliated
      columnar epithelium. Neurenteric cyst should be considered in the diagnosis of
      isolated cystic mass lesion at the lumbosacral region even in the absence of
      vertebral or visceral abnormality.

PMID- 17527054
TI  - Parietal intradiploic encephalocele--case report.
AB  - A 66-year-old man presented with a parietal intradiploic encephalocele
      manifesting as dizziness in June 2001. Skull radiography showed lytic change
      involving the right parietal bone. Computed tomography with bone window showed
      bone destruction associated with the right frontal lesion. Magnetic resonance
      imaging demonstrated a lesion in the parietal intradiploic space continuous with
      the right frontal lobe. The lesion was located near the central sulcus, so
      surgical biopsy carried the risk of motor dysfunction. Single photon emission
      computed tomography (SPECT) showed the same pattern of cerebral blood flow as
      normal brain tissue, so the neuroimaging diagnosis was encephalocele. The present
      case indicates that surgery may not be necessary in the absence of symptoms and
      neurological deficits. SPECT is very useful to identify encephalocele.

PMID- 17527055
TI  - [Evaluation of Ki-67 expression in recurrent cases of cholesteatoma].
AB  - OBJECTIVES: Recurrences are still a challenge despite appropriate techniques in
      cholesteatoma surgery. This study was designed to evaluate the level of Ki-67
      expression in recurrent cases of cholesteatoma. PATIENTS AND METHODS: The study
      included 32 patients (18 males, 14 females; mean age 34 years; range 12 to 63
      years) who underwent surgery for otitis media. Of these, 19 patients had
      cholesteatoma, and eight patients had recurrent cholesteatoma. Five patients who
      underwent tympanoplasty for chronic otitis media comprised the control group. All
      the patients with cholesteatoma underwent radical mastoidectomy. At surgery,
      tissue samples of cholesteatoma were taken and prepared for immunohistochemical
      staining. In controls, retroauricular skin samples were used. The two patient
      groups with cholesteatoma were compared with respect to Ki-67 expression.
      RESULTS: Increased cellular proliferation was detected in both groups of
      cholesteatoma. No significant difference was found between two cholesteatoma
      groups with respect to Ki-67 staining (p>0.05). Compared to the controls,
      patients with cholesteatoma and those with recurrent cholesteatoma had
      significantly higher levels of Ki-67 staining (p<0.05 and p<0.01, respectively).
      CONCLUSION: Our results suggest that, despite a higher degree of proliferation in
      recurrent cholesteatoma cases, treatment failures may be mainly associated with
      the surgical technique, accompanying infections, and the type of cholesteatoma.

PMID- 17527056
TI  - [An evaluation of parotid gland masses].
AB  - OBJECTIVES: We retrospectively evaluated patients who underwent surgery for
      parotid gland masses. PATIENTS AND METHODS: A total of 50 patients (25 females,
      25 males; mean age 48.5 years; range 18 to 76 years) who underwent surgery for
      parotid gland masses were evaluated with regard to age, sex, preoperative
      diagnostic methods, histopathologic diagnoses, and surgical techniques. RESULTS:
      Preoperative diagnostic studies included ultrasonography, fine-needle aspiration
      biopsy, computed tomography, and magnetic resonance imaging. Histopathological
      diagnoses were benign in 33 patients (66%), malignant in nine patients (18%), and
      tumor-like pathologies in eight patients (16%), the most common being pleomorphic
      adenoma (n=28, 56%), Warthin's tumor (n=4, 8%), and squamous cell carcinoma (n=4,
      8%). Superficial and total parotidectomies were performed in 40 (80%) and 10
      (20%) patients, respectively. Nine patients with malignant tumors also had neck
      dissection and postoperative radiotherapy. Mortality occurred in one patient with
      metastasis to the parotid gland. One patient with lipoma developed recurrence two
      years after surgery. Follow-up was five years in 28 patients (56%), three years
      in 12 patients (24%), and two years in five patients (10%). Complete and
      transient facial paralysis developed in 10 patients and five patients following
      total and superficial parotidectomy, respectively. CONCLUSION: Superficial
      parotidectomy is the minimal surgery for parotid gland masses. If the deep lobe
      of the gland is involved, total parotidectomy should be performed with
      preservation of the facial nerve. In malignant tumors, neck dissection and
      postoperative radiotherapy should be added.

PMID- 17527057
TI  - [Screening of the mitochondrial 12S rRNA (MTRNR1) gene in probands with
      sensorineural hearing loss].
AB  - OBJECTIVES: We investigated mitochondrial DNA 12S rRNA (MTRNR1) gene mutations as
      a cause of hearing loss in probands with or without a history of aminoglycoside
      use. PATIENTS AND METHODS: The study included 70 patients (40 females, 30 males;
      age range 3 to 42 years) with nonsyndromic sensorineural hearing loss. Eleven
      probands had a history of aminoglycoside use before the onset of hearing loss.
      All cases were first screened and found to be negative for the GJB2 (connexin 26)
      gene mutations. The m.1555A>G mutation was screened using the PCR-RFLP technique.
      The entire 12S rRNA gene was later screened with the PCR-TTGE technique followed
      by direct sequencing. RESULTS: Of 11 patients with a history of aminoglycoside
      use, one patient was found to have the m.1555A>G mutation. Two probands with no
      history of aminoglycoside use exhibited the m.750A>G polymorphism. No pathogenic
      base substitutions were detected in the remaining patients. CONCLUSION: Apart
      from the common aminoglycoside ototoxicity-related DNA change, m.1555A>G, we
      could not identify a common mitochondrial 12S rRNA mutation associated with
      hearing loss in Turkey. Screening of larger series may document rare alterations.

PMID- 17527058
TI  - [Lipid peroxidation and antioxidant levels in patients with laryngeal carcinoma].
AB  - OBJECTIVES: Reactive oxygen species (ROS) play an important role in the
      pathogenesis of cancer. The aim of this study was to investigate the extent of
      lipid peroxidation and ROS in laryngeal cancer tissues. PATIENTS AND METHODS: We
      determined glutathione (GSH) and malondialdehyde (MDA) activities as markers of
      lipid peroxidation in laryngeal tumor specimens and tumor-free adjacent tissues
      of 30 patients with squamous cell carcinoma. RESULTS: Compared to the tumor-free
      specimens, the level of GSH was significantly low (p<0.001) whereas MDA, a lipid
      peroxidation product, showed a significant increase (p<0.01) in cancer tissues.
      No significant differences were found in MDA and GSH levels between patients with
      early (n=14) and advanced (n=16) tumor stages (p>0.05). CONCLUSION: Decreased
      antioxidant capacity of laryngeal cancer tissues results in elevation of free
      oxygen radicals and increased lipid peroxidation. Free radical metabolism may be
      involved in the pathogenesis of laryngeal cancers.

PMID- 17527059
TI  - [Transnasal endoscopic repair of choanal atresia].
AB  - OBJECTIVES: We evaluated the results of endoscopic repair for choanal atresia.
      PATIENTS AND METHODS: Ten patients (2 males, 8 females) underwent transnasal
      endoscopic repair for choanal atresia. Involvement was unilateral in five cases
      and bilateral in five cases. Unilateral patients were treated at a mean age of
      22.6 years (range 1 to 44 years), while bilateral cases were treated within the
      first six days of life. Two patients with bilateral involvement had associated
      polydactyl and tracheoesophageal fistula, respectively. The mean follow-up period
      was 26 months (range 8 to 56 months). RESULTS: No postoperative complications
      such as significant hemorrhage, injury to the skull base, cerebrospinal fluid
      fistula, septal perforation, or granulation tissue formation were encountered.
      All the patients had choanal patency at the end of six months. CONCLUSION:
      Endoscopic repair of choanal atresia is effective in both unilateral and
      bilateral cases.

PMID- 17527060
TI  - Endoscopic transnasal sphenoidotomy with or without ethmoidectomy.
AB  - OBJECTIVES: We evaluated endoscopic transnasal sphenoidotomy (ETNS) with or
      without ethmoidectomy in patients with inflammatory sphenoid sinus disease
      (ISSD). PATIENTS AND METHODS: A retrospective review was conducted in 42 patients
      (17 males, 25 females; mean age 41 years; range 17 to 67 years) who underwent
      ETNS with (n=37) or without (n=5) ethmoidectomy for ISSD. The disase was staged
      according to our staging system based on computed tomography findings. RESULTS:
      Postnasal drainage was the most common symptom (n=37, 88.1%). Chronic
      rhinosinusitis was accompanied by sinonasal polyps in 25 patients (59.5%). Five
      patients (11.9%) had isolated sphenoid disease and 16 patients (38.1%) had
      unilateral disease. Five patients (11.9%) had stage 1, 15 patients (35.7%) had
      stage 2, and 22 patients (52.4%) had stage 3 disease. Surgery involved 68 sides.
      Ethmoidectomy was used in 63 sides of 37 patients, eight of whom required a
      supplementary procedure. At least one complication was seen in eight patients
      (19%), including severe perioperative hemorrhage (n=2), early postoperative
      hemorrhage (n=2), minor injuries to the lamina papyracea (n=4), and synechiae
      (n=5). CONCLUSION: In patients with isolated ISSD, the direct approach to the
      sphenoid sinus by ETNS without ethmoidectomy is a favorable technique, whereas
      ETNS with ethmoidectomy is necessary for patients with concurrent disease in
      other paranasal sinuses.

PMID- 17527061
TI  - [Sensitivity and specificity of fine needle aspiration biopsy in parotid masses].
AB  - OBJECTIVES: We aimed to determine the sensitivity and specificity of fine needle
      aspiration biopsy (FNAB) in patients with parotid masses. PATIENTS AND METHODS:
      The study included 29 patients (15 males, 14 females; mean age 52 years; range 20
      to 83 years) who underwent FNAB and parotidectomy for parotid masses. After a
      detailed history taking, otorhinolaryngologic and systemic examinations were
      performed. Neck ultrasonography and, when needed, neck computed tomography were
      used. Superficial parotidectomy was performed in 20 patients and total
      parotidectomy in nine patients. RESULTS: The results of FNAB were reported as
      benign in 21 patients (72.4%), malignant in six patients (20.7%), and suspicious
      in two patients (6.9%). Postoperative histopathologic diagnoses were reported as
      benign in 17 patients (58.6%) and malignant in 12 patients (41.4%). The
      sensitivity and specificity rates for FNAB were 54.6% and 100%, respectively. The
      most common histopathological diagnosis was pleomorphic adenoma (n=7, 24.1%),
      followed by mucoepidermoid carcinoma (n=4, 13.8%), and Warthin's tumor (n=3,
      10.3%). CONCLUSION: Preoperative FNAB for parotid masses plays an important role
      in planning surgery.

PMID- 17527062
TI  - [The effect of topical mitomycin-C application before or after incisional
      myringotomy on patency times of guinea pig tympanic membrane perforations].
AB  - OBJECTIVES: The aim of this study was to investigate the effect of topical
      mitomycin-C application before or after incisional myringotomy on patency times
      and to asess its use as an alternative to ventilation tube insertion. MATERIALS
      AND METHODS: Nineteen guinea pigs were divided into two groups. In the study
      group (n=11), mitomycin-C was applied in a concentration of 0.4 mg/ml over the
      perforation for five minutes before (n=6) or after (n=5) incisional myringotomies
      in both ears. Control animals (n=8) received 0.1 ml 0.09% NaCl for the same
      duration. Evaluations were made on days 1, 3, 5, 7, 10, 14, and 21. The patency
      times, otorrhea, and other complications were recorded. RESULTS: Compared to
      controls (7.0+/-1.5 days), the mean patency times of perforations were
      significantly longer in mitomycin-C treated groups before (11.6+/-5.2 days) and
      after (14.2+/-4.7 days) incisional myringotomies (p<0.05). Patency times did not
      differ significantly between the two mitomycin-C groups. None of the ears
      exhibited permanent perforation. CONCLUSION: The length of patency provided by
      mitomycin-C is not sufficient for optimal ventilation in otitis media with
      effusion. However, in cases requiring shorter patency times, mitomycin-C
      application before or after myringotomy may be an alternative to ventilation tube
      insertion.

PMID- 17527063
TI  - [Lipoid proteinosis in the mouth and laryngeal structures: a case report].
AB  - Lipoidproteinosis is an uncommon autosomal recessive disorder characterized by
      accumulation of hyaline material in the skin, oral and laryngeal mucosa. A 23
      year-old woman presented with complaints of hoarseness and dryness of the mouth.
      Yellowish papular deposits were noted in the oral and laryngeal mucosa on
      physical examination, and in vocal cords and laryngeal structures during
      laryngoscopy. The lesions were removed and histopathologic diagnosis was made as
      lipoidproteinosis. A slight improvement was obtained in hoarseness. A control
      examination after two years showed an increase in the extent of hoarseness and
      new deposits in the vocal cords. The lesions were removed by microlaryngeal
      surgery.

PMID- 17527064
TI  - [Multiple osteomas in the frontal and ethmoid sinuses: a case report].
AB  - Osteomas are the most common benign tumors of the paranasal sinuses. They may be
      seen at all ages and show a male preponderance. A 54-year-old male patient
      presented with a complaint of nasal obstruction. Computed tomography of the
      paranasal sinuses showed three osteomas, nearly 5 mm in size, in both ethmoid
      sinuses and the right frontal sinus. Inquiry into the Gardner's syndrome was
      negative. No surgical treatment was performed at the patient's discretion. To our
      knowledge, the presence of multiple osteomas in the frontal and ethmoid sinuses
      has not been reported in the English literature.

PMID- 17527065
TI  - Hemangiopericytoma of the parotid gland: a case report.
AB  - Hemangiopericytomas are uncommon neoplasms of vascular origin that mostly arise
      from extremities, retroperitoneum, and pelvic fossa. They are rarely found in the
      parotid gland. A 35-year-old female patient presented with a swelling in the
      right preauricular region. Fine-needle aspiration biopsy performed twice yielded
      an extraordinary amount of blood. A cytological diagnosis could not be made.
      Computed tomography showed a homogenous, well-shaped mass in the parotid gland.
      Superficial parotidectomy was performed. Histopathological diagnosis was made as
      hemangiopericytoma. No evidence for local recurrence or distant metastasis was
      seen within a follow-up of 36 months.

PMID- 17527066
TI  - [Classic Kaposi's sarcoma of the tongue: a case report].
AB  - An 81-year-old male patient presented with a painful mass in the tongue that
      showed a progressive growth within the past two months. Examination revealed a
      polypoid mass in the midline of the tongue, purple in color, and 1.5x1.5 cm in
      size. There was no palpable lymph node on neck examination. An excisional biopsy
      was performed with adequate surgical margins. The histopathological diagnosis was
      Kaposi's sarcoma. Clinical and radiological evaluations did not show any systemic
      involvement. An HIV test was negative. He was referred to the medical oncology
      department. No recurrence was detected during a year follow-up.

PMID- 17527067
TI  - [Sudden hearing loss in a patient with a 3-mm acoustic tumor].
AB  - Sudden sensorineural hearing loss (SNHL) accounts for 1% of all SNHL cases. It
      has been reported that acoustic neuroma may be present up to 47.5% of patients
      with sudden SNHL. A 55-year-old man presented with sudden hearing loss in his
      left ear of 45-day history. Audiologic and transient evoked otoacoustic emission
      tests showed near-total hearing loss and absence of emissions in the left ear,
      respectively. Electronystagmography showed left canal paralysis and lack of
      response to the Kobrak test. The interpeak interval I-V latency and interaural
      amplitude differences in wave V latency were prolonged in auditory brainstem
      response. Computed tomography showed an increase in the diameter of the left
      internal acoustic canal, and magnetic resonance imaging (MRI) revealed an
      intracanalicular mass, 3 mm in size, originating from the left cochlear nerve.
      Another mass (18x17 mm) was detected that filled the right pontocerebellar
      cistern, suggesting a meningioma, but this was not thought to exert an obvious
      shift effect contributing to the development of left-sided hearing loss. Despite
      treatment with a tapered course of fluocortolone for 18 days the patient's
      hearing level did not change. He was included in a follow-up with MRI at six
      month intervals.

PMID- 17527068
TI  - Primary carcinosarcoma of the liver: clinicopathologic features of 5 cases and a
      review of the literature.
AB  - Carcinosarcoma of the liver is very rare worldwide. The terminology and
      pathogenesis of hepatic carcinosarcoma remain controversial issues. In this
      article, we studied the clinicopathologic features of 5 cases of hepatic
      carcinosarcomas (matching the World Health Organization definition), analyzed the
      clinical data, histologic and immunohistochemical (IHC) results, and discussed
      the terminology, pathologic differential diagnoses, pathogenesis, and prognosis.
      The patients were 40 to 68 years old, and included 4 males and 1 female. All
      patients were Hepatitis B surface antigen positive with para-tumorous cirrhosis.
      The largest dimensions of the neoplasms ranged from 6.0 to 14.0 cm. Satellite
      nodules, portal vein tumor thrombi, direct invasion into local tissues (right
      diaphragm, right adrenal gland, and gastric wall) as well as metastatic foci in
      lungs and abdominal lymph nodes were identified. Pathologically, the neoplasms
      consisted of carcinomatous and sarcomatous components. The carcinomatous
      components were exclusively conventional hepatocellular carcinomas in all 5
      cases, whereas the sarcomatous components exhibited complex features. Confirmed
      by IHC studies, the sarcomatous elements in different cases included
      rhabdomyosarcomas, malignant fibrous histiocytomas, fibrosarcoma, and poorly
      differentiated spindle cells without distinctive differentiation. Furthermore,
      the sarcomatous elements in these 5 neoplasms stained negative for all the
      epithelial markers we applied for IHC staining, which support the pathologic
      diagnosis of carcinosarcoma rather than sarcomatoid carcinoma. The presence of
      transitional zones between carcinomatous and sarcomatous components may support
      the transformation theory. Four patients with palliative hepatectomy died within
      6 months, whereas 1 patient is still alive 21 months after radical resection. The
      poor prognosis of hepatic carcinosarcoma may be due to their highly invasive and
      metastatic features. Radical resection of early stage hepatic carcinosarcoma may
      contribute to a relatively optimistic prognosis.

PMID- 17527069
TI  - Intratubular large cell hyalinizing sertoli cell neoplasia of the testis: a
      report of 8 cases of a distinctive lesion of the Peutz-Jeghers syndrome.
AB  - We report the clinical and pathologic features of 8 boys with Peutz-Jeghers
      syndrome who had distinctive testicular lesions. The patients were 4 to 13 years
      of age (mean, 6.5 y), and all had gynecomastia, which was the presenting feature
      in 7. Physical examination demonstrated bilateral testicular enlargement in the
      absence of a discrete mass. Advanced bone age and elevated serum estradiol were
      demonstrated in 3 and 4 cases, respectively. Testicular biopsy, performed in all
      cases, usually showed no gross abnormality, but on microscopic examination there
      were patchily distributed clusters of expanded seminiferous tubules that
      contained large Sertoli cells with vacuolated to eosinophilic cytoplasm admixed
      with globular deposits of basement membrane that extended from a thickened
      peritubular basement membrane. Small, focal calcifications occurred in 3 cases;
      no invasive tumor was present in any of the cases. Follow-up was available in 5
      patients after biopsy, and none showed evidence of progression at 10 months to 5
      years (median, 4 y). Review of the previously reported cases of testicular
      lesions in Peutz-Jeghers patients verified a low frequency of invasive tumors
      (27%) and no known case with metastasis. The testicular lesions seen in patients
      with Peutz-Jeghers syndrome mostly represent multifocal intratubular neoplasia of
      large Sertoli cells with unique morphology distinct from other lesions such as
      the large cell calcifying Sertoli cell tumor and sex cord tumor with annular
      tubules. The process usually remains confined to the tubules for prolonged
      intervals (years), but it may occasionally progress to invasive large cell
      Sertoli cell tumors with or without associated calcification. This indolent
      course justifies management by careful follow-up, including ultrasound
      examination, rather than orchiectomy in the majority of cases. Orchiectomy is
      indicated when there is evidence of an invasive tumor and may be necessary to
      control hormonal manifestations.

PMID- 17527070
TI  - Embryonic stem cell transcription factor signatures in the diagnosis of primary
      and metastatic germ cell tumors.
AB  - The core embryonic stem cell transcription factors (TFs) OCT3/4 (OCT4), NANOG,
      and SOX2 have shared as well as nonoverlapping roles in stem cell growth and
      differentiation. These same TFs are also expressed in various types of human germ
      cell tumors (GCTs), implicating them in regulation of tumor growth and
      differentiation. Although NANOG and OCT3/4 are sensitive and specific markers for
      seminoma and embryonal carcinoma, neither factor aids in the clinically important
      distinction of seminomatous from nonseminomatous tumors. In contrast, expression
      profiling data suggest that SOX2 may help with this distinction. To determine if
      a panel of embryonic stem cell TFs (NANOG, OCT3/4, and SOX2) can facilitate the
      identification and distinction of seminomatous from nonseminomatous GCTs, we
      evaluated their expression by immunohistochemistry in primary testicular (n=41)
      and metastatic retroperitoneal (n=43) GCTs. Our results confirm NANOG and OCT3/4
      as sensitive and specific markers for primary seminoma and embryonal carcinoma
      and demonstrate the novel finding that NANOG is a marker for metastatic GCTs. In
      addition, SOX2 is expressed in embryonal carcinoma but not pure seminoma and is
      therefore a useful diagnostic marker for distinguishing seminomatous and
      nonseminomatous GCTs. In summary, we find that the embryonic stem cell TF
      signature of seminoma is NANOG+, OCT3/4+, and SOX2-, whereas embryonal carcinoma
      is NANOG+, OCT3/4+, and SOX2+, and expect these immunohistochemical profiles will
      facilitate the diagnosis of both primary and metastatic GCTs.

PMID- 17527071
TI  - Microsatellite instability in endometrioid type endometrial adenocarcinoma is
      associated with poor prognostic indicators.
AB  - Microsatellite instability (MSI) has been reported in 25% to 45% of sporadic
      endometrial carcinoma. The clinicopathologic and molecular characteristics of MSI
      high phenotype in colorectal and gastric carcinomas have been widely
      investigated; however, the clinicopathologic impact of MSI on endometrial
      carcinomas remained unclear. This study was performed to determine the
      clinicopathologic and molecular significance of MSI in endometrial carcinomas. We
      analyzed the MSI status using National Cancer Institute-recommended 5
      microsatellite markers, and the immunohistochemical profiles of various
      regulatory proteins of cell cycle and apoptosis using tissue microarray in 100
      endometrial carcinomas. The results were compared between MSI-high and MSI(-)
      groups as for the traditional clinicopathologic prognostic parameters and the
      immunoreactivities of various regulatory proteins. We especially focused on the
      endometrioid type adenocarcinoma to exclude the bias from nonendometrioid type
      adenocarcinomas with more aggressiveness and a close association with MSI(-)
      phenotype. The incidence of MSI-high phenotype was significantly higher in
      endometrioid type than in nonendometrioid serous type (20% vs. 0%, P<0.001). It
      showed orderly increase in the frequencies of MSI-high phenotype in higher
      histologic grade (13% vs. 21% vs. 50% in histologic grade I, II, and III,
      P=0.039). The MSI-high phenotype was related with the presence of lymphovascular
      invasion (P=0.008), deep myometrial invasion (P=0.040), and the higher clinical
      stages (P=0.018) independent of tumor grade. We also found a correlation between
      MSI-high phenotype and higher cyclin A and skp2 immunoreactivity (P=0.03 and
      0.05, respectively), known to be the poor prognostic molecular indicators.
      According to these results, the MSI may represent the poor prognostic impact on
      the endometrioid type endometrial adenocarcinoma.

PMID- 17527072
TI  - Ovarian mucinous tumors associated with mature cystic teratomas: morphologic and
      immunohistochemical analysis identifies a subset of potential teratomatous origin
      that shares features of lower gastrointestinal tract mucinous tumors more
      commonly encountered as secondary tumors in the ovary.
AB  - Most primary ovarian mucinous tumors are of surface epithelial-stromal origin and
      exhibit diffuse expression of cytokeratin 7 (CK7) combined with variable
      expression of cytokeratin 20 (CK20); this immunoprofile distinguishes them from
      most lower gastrointestinal tract tumors secondarily involving the ovaries. The
      uncommon ovarian mucinous tumors of germ cell (teratomatous) origin have not been
      extensively evaluated to determine the utility of these markers and other markers
      of intestinal differentiation for distinguishing these tumors from metastatic
      gastrointestinal tract mucinous tumors. Immunohistochemical expression of CK7,
      CK20, CDX2, and villin was assessed in 44 ovarian mucinous tumors associated with
      a mature cystic teratoma. All cases lacked evidence of a nonovarian primary
      mucinous tumor. All mucinous tumors were unilateral; 6 cases had bilateral
      teratomas. All tumors displayed gastrointestinal-type mucinous differentiation,
      with epithelium that was commonly goblet cell-rich or hypermucinous; 21 were
      associated with pseudomyxoma ovarii and 3 of these had pseudomyxoma peritonei.
      Tumor architecture ranged from purely cystadenomatous (n=24), to proliferative
      (n=13), to carcinomatous (n=6); some tumors had admixtures of these patterns. One
      tumor had a goblet cell carcinoidlike pattern with pseudomyxoma ovarii. Three
      carcinomas had a signet ring cell component. Cystadenomatous tumors without
      pseudomyxoma ovarii (n=15) exhibited all possible CK7/CK20 coordinate expression
      profiles with nearly equal frequency. All proliferative tumors without
      pseudomyxoma ovarii (n=8) expressed CK7, most often in combination with CK20
      expression. All cystadenomatous and proliferative tumors with pseudomyxoma ovarii
      (n=9 and n=5) were CK7-/CK20+. All carcinomatous tumors had pseudomyxoma ovarii;
      3 were CK7-/CK20+, 2 were CK7+/CK20+, and 1 was CK7+/CK20-. The presence of
      pseudomyxoma ovarii was significantly associated with a CK7-/CK20+ profile (86%
      with pseudomyxoma ovarii vs. 13% without, P<0.0001), CDX2 positivity (79% vs. 0%,
      P<0.0001), and villin positivity (57% vs. 5%, P=0.0009). A subset of mucinous
      tumors associated with mature cystic teratomas exhibiting morphologic and
      immunohistochemical features of lower intestinal tract-type mucinous tumors may
      be teratomatous in origin. In practice, the more common diagnosis of secondary
      involvement by a lower intestinal tract mucinous tumor should be addressed in the
      pathology report and in subsequent clinical evaluation; interpretation as a true
      primary ovarian mucinous tumor of teratomatous origin can be considered as an
      alternative diagnosis when evaluation and follow-up fail to identify a nonovarian
      source of the mucinous tumor. Those tumors having CK7 expression with or without
      CK20 expression may be derived from upper gastrointestinal tract-type or
      sinonasal-type teratomatous elements but could be independent tumors of surface
      epithelial-stromal origin.

PMID- 17527073
TI  - Solitary fibrous tumor on needle biopsy and transurethral resection of the
      prostate: a clinicopathologic study of 13 cases.
AB  - One of the least commonly encountered spindle cell tumors seen on prostatic
      needle biopsy or transurethral resection (TUR) of the prostate is solitary
      fibrous tumor (SFT). We studied 13 cases of SFTs identified on either prostate
      needle biopsy (n=9) or TUR of the prostate (n=4). Mean patient age at diagnosis
      was 63 years (range: 46 to 75 y; median: 65 y). Twelve men presented with urinary
      tract symptoms and 1 patient was biopsied during work-up of bone metastases. Ten
      cases were SFTs originating in the prostate, 2 cases arose between the prostate
      and rectum extending into the prostate (n=2), and 1 case was a pelvic mass
      without infiltration of the prostate. In 9 cases, a complete tumor resection was
      attempted by cystoprostatectomy (n=2), radical prostatectomy (n=4), pelvic
      exenteration (n=2), or pelvic tumor resection (n=1). Enucleation (n=1) and TUR
      (n=1) were performed in 2 other cases. Tumor sizes ranged from 8.5 to 15 cm in 7
      radically resected cases. Mitotic rates were 3 to 5 per 10 high power fields in 5
      cases, with the remaining cases having either rare (n=4) or no mitoses (n=4).
      Seven cases demonstrated areas of necrosis. Based on a combination of increased
      cellularity, mitotic activity, necrosis, nuclear pleomorphism, and
      infiltrativeness, 4 prostatic SFTs were malignant, 4 were benign, and 2 were
      borderline. Of the 3 non-prostatic SFTs, 1 was malignant and 2 were borderline.
      All tumors but 1 were immunoreactive for CD34 (n=12). Material for additional
      immunohistochemistry was available for the majority of cases with positive stains
      for Bcl-2 (11/11), CD99 (7/10), beta-catenin (5/10), and c-kit (0/11). Three SFTs
      demonstrated >or=10% p53 immunoreactivity including 1 tumor with 50% positivity;
      and 3 cases had Ki-67 rates of >or=20%. Although all SFTs were initially
      clinically considered to be of prostatic origin, some of the cases arose in the
      pelvis with secondary involvement of the prostate. Approximately 50% of prostatic
      SFTs were malignant. Even in the prostatic and nonprostatic SFTs with no overt
      malignant features, sometimes it was necessary to remove the prostate and in some
      instances the adjacent organs because of the large size of the tumors. SFTs must
      be differentiated from other spindle cell neoplasms of the prostate especially
      from gastrointestinal stromal tumors that may arise from the rectal wall with
      invasion of the prostate or from the region between the rectum and the prostate.

PMID- 17527074
TI  - Positive-block ratio in radical prostatectomy specimens is an independent
      predictor of prostate-specific antigen recurrence.
AB  - Tumor volume has been considered an important variable in determining the
      probability of prostate-specific antigen (PSA) recurrence in prostatic
      adenocarcinoma. There have been many studies that have tried to determine an
      appropriate method of calculating tumor volume, but no single methodology has
      been agreed upon. We tested the hypothesis that the ratio of tumor positive
      tissue blocks to the total number of blocks submitted (positive-block ratio) can
      be used as an independent prognostic indicator for PSA recurrence. We analyzed
      504 patients who underwent total radical retropubic prostatectomy between 1990
      and 1998. None of the patients had preoperative radiation or androgen-deprivation
      therapy. Clinical records were reviewed. The mean positive-block ratio was 0.44
      (median, 0.43; range, 0.05 to 1.0). The positive block-ratio was significantly
      associated with Gleason score, pathologic stage, surgical margin status,
      extraprostatic extension, seminal vesical invasion, lymph node metastasis,
      perineural invasion, and preoperative serum PSA level (all P<0.001). Using a
      multivariate Cox regression model, controlling for pathologic stage, Gleason
      score, lymph node metastasis, and surgical margin status, positive-block ratio
      was an independent predictor of PSA recurrence (hazard ratio, 2.3; 95% confidence
      interval, 1.06-4.83; P=0.03). Five-year PSA recurrence-free survival was 67% for
      those patients with positive-block ratio <or=0.43, as compared with 42% those
      with positive-block ratio >0.43 (P<0.001). Positive-block ratio is an independent
      predictor of PSA recurrence and this simple method of tumor measurement seems to
      be promising for quantifying tumor volume if our findings are validated by
      subsequent reports.

PMID- 17527075
TI  - TMPRSS2-ERG fusion prostate cancer: an early molecular event associated with
      invasion.
AB  - Prostate cancer (PCA) is one of the most prevalent cancers and a major leading
      cause of morbidity and mortality in the Western world. The TMPRSS2-ERG fusion was
      recently identified as a common recurrent chromosomal aberration in this
      malignancy. In our study, we interrogated a broad spectrum of benign, precursor,
      and malignant prostatic lesions to assess the TMPRSS2-ERG fusion status using a
      multicolor interphase fluorescence in situ hybridization assay. Samples from
      hospital-based cohorts consisted of 237 clinically localized PCA, 34 hormone
      naive metastases, 9 hormone refractory metastases, 26 high grade prostatic
      intraepithelial neoplasia lesions, 15 samples of benign prostatic hyperplasia, 38
      of proliferative inflammatory atrophy, and 47 of benign prostatic tissue. The
      TMPRSS2-ERG fusion was present in 48.5% of clinically localized PCA, 30% of
      hormone naive metastases, 33% of hormone refractory metastases, and in 19% of
      high grade prostatic intraepithelial neoplasia lesions in intermingling to cancer
      foci. Almost all these fusion positive cases show a homogenous distribution of
      the fusion pattern. In contrast, none of the other samples harbored this genetic
      aberration. If we consider the high incidence of PCA and the high frequency of
      this gene fusion, TMPRSS2-ERG is the most common genetic aberration so far
      described in human malignancies. Furthermore, its clinical application as a
      biomarker and ancillary diagnostic test is promising given its high specificity.

PMID- 17527076
TI  - Immunohistochemical antibody cocktail staining (p63/HMWCK/AMACR) of ductal
      adenocarcinoma and Gleason pattern 4 cribriform and noncribriform acinar
      adenocarcinomas of the prostate.
AB  - Overexpression of alpha-methylacyl coenzyme A racemase (AMACR) in combination
      with absence of basal cell markers [ie, p63 and high molecular weight cytokeratin
      (HMWCK)] is typical of classic acinar prostatic adenocarcinoma. We studied the
      expression and diagnostic utility of p63/HMWCK/AMACR immunohistochemical cocktail
      staining in ductal adenocarcinoma and cribriform Gleason pattern 4 acinar
      prostate cancer and compared it to noncribriform Gleason pattern 4 acinar
      prostate cancer. One to 4 representative formalin-fixed paraffin-embedded
      archival tissue blocks from 62 radical prostatectomy specimens harboring prostate
      cancer of ductal (n=51), cribriform Gleason pattern 4 acinar (n=27), and
      noncribriform Gleason pattern 4 acinar adenocarcinoma (n=48) were included in
      this study. Immunohistochemistry was performed using a triple stain of AMACR,
      p63, and HMWCK. Only staining that was moderate or strong was considered
      positive. The percentage of staining intensity and the presence of occasional
      basal cells positive with p63/HMWCK were recorded in each histologic type of
      prostatic adenocarcinoma. Seventy-seven percent of ductal prostatic
      adenocarcinoma, 67% of cribriform acinar prostatic carcinoma, and 81% of
      noncribriform acinar prostatic carcinoma showed positive staining for AMACR.
      There was no statistically significant difference between AMACR staining among
      the 3 histologic types, although there was a trend for noncribriform acinar
      prostatic carcinoma to have greater expression of AMACR than cribriform acinar
      prostatic carcinoma (P=0.07). Staining was often heterogeneous, varying in
      staining intensities within the same histologic type of carcinoma. Basal cells
      were detectable by p63 and HMWCK in a patchy fashion in 31.4% (16/51) of ductal
      and 29.6% (8/27) of cribriform acinar carcinomas compared with 2.1% (1/48) of
      noncribriform acinar carcinomas. In summary: (1) the majority of prostatic ductal
      and cribriform acinar carcinomas strongly expressed AMACR, however,
      subpopulations of these prostatic carcinoma were either completely negative or
      only weakly positive; (2) AMACR staining was often heterogeneous in intensity in
      the same histologic type of tumor, even within the same case; (3) patchy basal
      cell staining in noncribriform acinar prostatic carcinoma is rare. In contrast,
      remnants of basal cells identified by p63/HMWCK were seen in a patchy fashion in
      a significant minority of both ductal and cribriform acinar prostatic
      adenocarcinoma, which most likely represents intraductal spread of tumor.

PMID- 17527077
TI  - Correlation between histology and PAX/FKHR fusion status in alveolar
      rhabdomyosarcoma: a report from the Children's Oncology Group.
AB  - At the molecular level, alveolar rhabdomyosarcomas (ARMS) are characterized by 3
      mutually exclusive PAX/FKHR conditions: PAX3/FKHR fusion (present in 60% of
      cases), PAX7/FKHR fusion (present in 20%), and PAX/FKHR fusion-negativity
      (present in 20%). The possibility of morphologic variation among these molecular
      subtypes has not been investigated. We undertook a blinded retrospective study of
      65 cases of ARMS (16 PAX/FKHR fusion-negative, 36 PAX3/FKHR-positive, and 13
      PAX7/FKHR-positive by routine reverse transcription-polymerase chain reaction).
      We evaluated cytohistologic parameters such as microcyst formation, solid foci,
      differentiation, giant cell formation, anaplasia, nuclear grade,
      mitosis/karyorrhexis index, rosette formation, geographic necrosis, presence and
      amount of rhabdomyoblastic differentiation, and the presence of foci resembling
      embryonal rhabdomyosarcoma. We analyzed the results using a simple chi formula.
      Of these features, only totally solid alveolar architecture reached significance
      (P=0.00014), with 7 of 16 PAX/FKHR-negative cases lacking this feature, compared
      with 0 of 36 PAX3/FKHR cases and 2/13 PAX7/FKHR cases. These preliminary results
      indicate that in general, only totally solid alveolar architecture in ARMS may
      predict the absence of a PAX/FKHR fusion. No features seemed to predict the
      presence of a particular fusion type. Our results suggest that histologic
      assessment of ARMS has limited correlation with PAX/FKHR fusion status.

PMID- 17527078
TI  - Intrahepatic clear cell cholangiocarcinoma: immunohistochemical aspects in a very
      rare type of cholangiocarcinoma.
AB  - Clear cell cholangiocarcinoma is a very unusual variant of peripheral bile duct
      carcinoma. We present 3 cases on which we performed a broad spectrum of
      immunohistochemical analysis. The tumors showed a glandular and trabecular growth
      pattern with abundant desmoplastic stroma and clear cell change of about 80% of
      the tumor cells. Positive expression of CK7 indicated a cholangiocellular origin.
      A primary hepatocellular carcinoma and metastatic clear cell tumors of the
      kidney, gastrointestinal tract, and the thyroid gland were excluded by absence of
      CK20, CD10, HepPar1, and TTF1. No mucin could be detected within the cytoplasm of
      the clear cells. Electronmicroscopy revealed only a few glycogen granula, but
      numerous cytoplasmic lipoid vacuoles as a possible explanation for the clear cell
      phenotype. All 3 tumors exhibited positive expression of CD56 (NCAM) in a
      significant amount of the clear cells. Beside the clear cell component, one tumor
      also showed an adenocarcinomalike and a well-differentiated tubular component.
      CD56 expression was detected in all 3 tumor areas. This report of 3 cases
      demonstrates that clear cell cholangiocarcinomas are not only of unusual
      histomorphology. They also show CD56 expression which is a very uncommon finding
      for intrahepatic cholangiocarcinomas. As CD56 expression is also found in
      reactive bile ducts and bile duct adenomas, one may speculate that these rare
      neoplasms may originate from reactive bile ducts or cholangiomatous lesions.

PMID- 17527079
TI  - Prevalence and risk factors for gallbladder neoplasia in patients with primary
      sclerosing cholangitis: evidence for a metaplasia-dysplasia-carcinoma sequence.
AB  - Primary sclerosing cholangitis (PSC) carries an increased risk (10% to 20%) of
      hepatobiliary malignancy, especially cholangiocarcinoma (CC). Dysplasia,
      adenomas, and carcinomas of the gallbladder have been described in PSC but are
      less common than bile duct carcinomas. However, the prevalence and risk factors
      for gallbladder neoplasia among patients with PSC undergoing orthotopic liver
      transplantation (OLT) have not been well studied. We evaluated 72 gallbladders
      from 100 consecutive liver explants for PSC, including 66 cholecystectomies
      performed at the time of OLT and 6 performed before OLT. All specimens were
      totally embedded for histologic examination. We evaluated the following
      histologic features: presence of diffuse lymphoplasmacytic chronic cholecystitis,
      pyloric metaplasia, intestinal metaplasia, dysplasia (low-grade or high-grade),
      and adenocarcinoma. Gallbladder dysplasia and adenocarcinoma were correlated with
      several clinicopathologic parameters using Fisher exact test and t test,
      including: (1) sex, (2) age, (3) PSC duration, (4) inflammatory bowel disease
      (IBD) at time of OLT, and (5) concomitant bile duct dysplasia or carcinoma.
      Lymphoplasmacytic chronic cholecystitis was present in 35 (49%), pyloric
      metaplasia in 69 (96%), intestinal metaplasia in 36 (50%), dysplasia in 27 (37%;
      low-grade in 12 and high-grade in 15), and adenocarcinoma in 10 (14%; 2 with
      lamina propria invasion and 8 with invasion into muscularis or adventitia).
      Gallbladder carcinoma was associated with intrahepatic bile duct dysplasia
      (P=0.001), CC (P=0.023), and IBD (P=0.03). Gallbladder dysplasia was associated
      with hilar/intrahepatic bile duct dysplasia (P=0.0006), CC (P=0.028), IBD
      (P=0.0014), and older age at OLT (P=0.007). Neither gallbladder carcinoma nor
      dysplasia had a significant association with sex or PSC duration. These results
      indicate that complete histologic evaluation of gallbladders in patients
      undergoing transplantation for PSC yields high frequencies of inflammatory,
      metaplastic, and neoplastic changes. The strong correlation between gallbladder
      dysplasia/adenocarcinoma and bile duct dysplasia/CC supports the concept of a
      neoplastic "field effect" along the intrahepatic and extrahepatic biliary tract
      in PSC.

PMID- 17527080
TI  - Mesothelial cells in transbronchial biopsies: a rare complication with a
      potential for a diagnostic pitfall.
AB  - The presence of pleural tissue in transbronchial biopsies (TBs) is an incidental
      finding that has been rarely reported in the literature. It has the potential for
      causing wrong histologic diagnoses. Clinically, the significance of unintended
      pleural sampling by bronchoscopy is unknown. TBs containing mesothelial cells
      from 6 adult patients were studied using immunohistochemical stains. Clinical
      information was obtained with emphasis on the immediate postbronchoscopy period.
      The TBs were performed by 6 different bronchoscopists at 4 institutions because
      of pulmonary infiltrates in 5 patients and a mass lesion in 1 patient. All
      samples contained lung parenchyma and bronchial wall. They showed clusters of
      medium to large size polygonal cells with pink to amphophilic dense cytoplasm,
      round to oval nuclei, and prominent nucleoli. Some of the cells lined stroma and
      others were detached forming ribbons. They were initially disregarded,
      interpreted as carcinoma, judged as mesothelial cells, or interpreted as drug
      induced reactive epithelial cells. They were positive for cytokeratin and showed
      nuclear staining for calretinin. They were negative for TTF-1, S100, CEA, and
      CD68. However, in 1 case, CD-68 positive histiocytes were admixed with enlarged
      reactive mesothelial cells corresponding to the so-called nodular histiocytic
      mesothelial hyperplasia. Chest x-ray films performed the same day after
      bronchoscopy showed no pneumothorax. Incidental sampling of the pleura may occur
      during the performance of TB and mesothelial cells may mimic carcinoma,
      pneumocytes, or macrophages. It is important to be aware of the presence of
      mesothelial cells in clinically uncomplicated TB to avoid an erroneous diagnosis
      of malignancy.

PMID- 17527081
TI  - Role of human papillomavirus in squamous cell metaplasia-dysplasia-carcinoma of
      the rectum.
AB  - Primary colorectal squamous cell carcinoma (SCC) and squamous dysplasia are
      uncommon and little is known about their pathogenesis. Most have been reported in
      association with ulcerative colitis and other chronic disease states. Although
      cervical and anal SCC have been strongly linked to human papillomavirus (HPV)
      infection, the role of HPV in rectal squamous carcinoma has not been well
      examined. We evaluated 3 cases of primary rectal SCC for the presence of high
      risk HPV by immunohistochemistry for p16(INK4A), in situ hybridization, and
      polymerase chain reaction. HPV type 16 was detected by polymerase chain reaction
      in all cases. In addition, all cases exhibited diffuse strong reactivity for
      p16(INK4A) and punctate nuclear staining by Ventana HPVIII in situ hybridization.
      The presence of HPV 16 in all three cases suggests that high-risk HPV infection
      is a risk factor for rectal SCC, particularly in patients with underlying chronic
      inflammatory disease processes or altered immune status. Further studies are
      warranted to determine if SCC occurring more proximal in the colon are also HPV
      dependent or occur via another, HPV-independent pathway.

PMID- 17527082
TI  - Novel karyotypes in giant cell-rich lesions of bone.
AB  - Giant cell-rich lesions of bone, including giant cell tumor of bone, giant cell
      reparative granuloma (GCRG), and aneurysmal bone cyst (ABC), may have overlapping
      clinical, radiologic, and histopathologic features. In fact, GCRG and solid ABC
      are currently differentiated solely based on skeletal location. Prior cytogenetic
      studies have reported that telomeric associations are present in the majority of
      giant cell tumors of bone, whereas translocations involving 16q22 and/or 17p13
      are characteristic of ABCs. There is only one previously published karyotype of a
      GCRG, which revealed a reciprocal translocation, t(X;4)(q22;q31.3). We report 3
      cases of giant cell-rich bone lesions with novel karyotypes: one lesion located
      in the first metacarpal, a typical location for GCRG, was histologically
      consistent with a giant cell tumor and showed the following karyotype
      [46,XX,inv(2)(p13q21),t(inv2;11)(q21;q13)]; the second lesion, also a giant cell
      tumor of bone, in the sacrum showed the following karyotype
      [46,XX,r(9)(p24q34)[cp7]/46,idem,?r(16)(p13.3q24)[cp10]/46,XX]. The third lesion,
      a hard palate mass, had the histopathologic features of a GCRG and a karyotype
      showing a reciprocal translocation, 46,XY,t(2;10)(q23;q24). These findings
      suggest that at least a subset of GCRGs may be neoplastic and that these lesions
      differ cytogenetically from classic giant cell tumors of bone or solid ABC,
      although the latter entity is otherwise indistinguishable from reparative
      granuloma. Further cytogenetic characterization of giant cell-rich bone lesions
      may improve the utility of karyotyping as a tool in their differential diagnosis
      and may shed light on the pathogenetic relationship between these lesions.

PMID- 17527083
TI  - Multicentric sporadic gastrointestinal stromal tumors (GISTs) of the stomach with
      distinct clonal origin: differential diagnosis to familial and syndromal GIST
      variants and peritoneal metastasis.
AB  - Most sporadic gastrointestinal stromal tumors (GISTs) occur solitary, whereas a
      multicentric appearance is suspicious for a familial or syndromal setting such as
      with germline mutations of proto-oncogene tyrosine protein kinase Kit (KIT) or
      platelet derived growth factor receptor alpha (PDGFRA), or even for metastases.
      The aim of this study was to evaluate whether multicentric sporadic GISTs are of
      clonal origin. Four patients with 1 clinically apparent tumor (mean size 5.6 cm)
      and 1 to 3 further small incidental tumors (mean size 0.7 cm) were analysed by
      mutation analysis and comparative genomic hybridization for mutations of KIT and
      PDGFRA and chromosomal imbalances in their tumors. No clinicopathologic features
      have been found being indicative of one of the established familial or syndromal
      GIST variants. Each of the small GISTs were localized in the muscularis propria,
      and were visible from the serosal but not from the mucosal side. Different
      mutations of KIT and PDGFRA were present among individual tumors of each patient,
      and germline mutation of KIT and PDGFRA could be excluded. Comparative genomic
      hybridization revealed a mean count of 7 chromosomal imbalances in the clinically
      apparent tumors compared with a mean count of 0.3 in the small incidental
      counterparts. Sporadic GISTs can appear multicentric by coincidence. They are an
      important differential diagnosis to familial and syndromal GIST variants, or even
      to peritoneal metastases. Different mutations of KIT and PDGFRA among individual
      tumors in 1 patient refer to different clonal origin of multicentric sporadic
      GISTs. The type of mutation of KIT and PDGFRA was independent of tumor size,
      whereas small GISTs <1 cm rarely had genomic imbalances.

PMID- 17527084
TI  - Low frequency of molecular changes and tumor recurrence in inverted papillomas of
      the urinary tract.
AB  - AIM: Inverted papilloma (IP) of the urinary tract can be difficult to distinguish
      from noninvasive urothelial carcinoma with prominent inverted growth pattern
      (invNIUC). Ancillary markers may help to resolve such cases and clarify the
      reported malignant potential of some IPs. METHODS: Eighty-nine urothelial lesions
      initially diagnosed as IP were reviewed by 4 experienced urologic pathologists
      and studied immunohistochemically (Ki67, p53, CK20, MSH2, MLH1, and MSH6).
      Mutations of the FGFR3 gene, deletions (loss of heterozygosity) of 9p, 9q, and
      17p, microsatellite instability, and elevated microsatellite instability at
      selected tetranucleotides were also analyzed. RESULTS: Considerable interobserver
      variability in histopathologic diagnoses was noticed. Only 62 (69.7%) initial
      diagnoses were confirmed by the review pathologists whereas 23 tumors (25.8%)
      were redefined as invNIUC. Molecular analyses revealed infrequent alterations in
      IPs, including microsatellite instability (1.8%), elevated microsatellite
      instability at selected tetranucleotides (13.2%), FGFR3 mutations (9.8%), 9p
      deletions (3.9%), 9q deletions (13.2%), 17p deletions (5.1%), nuclear p53
      accumulation (18.9%), and aberrant immunostaining for MSH2 (5.8%), MLH1 (11.8%),
      and MSH6 (3.8%). IP and invNIUC differed in FGFR3 mutations and Ki-67 labeling
      index (P<0.001 each), and 9q loss of heterozygosity (P=0.03). There were fewer
      recurrences in IP (5.4%) compared with invNIUC (40.9%; P<0.0001). CONCLUSIONS: IP
      is a benign lesion that lacks specific genetic alterations found in exophytic
      noninvasive papillary urothelial tumors. These lesions could be reactive in
      nature, perhaps secondary to chronic inflammation or a neoplastic process that
      lack specific genetic alterations. Nevertheless given the clinical and molecular
      data of this study a conservative clinical approach is appropriate.

PMID- 17527085
TI  - Immunohistochemical analysis of langerin in langerhans cell histiocytosis and
      pulmonary inflammatory and infectious diseases.
AB  - Pulmonary Langerhans cell histiocytosis (LCH) is an idiopathic condition
      affecting predominantly adult smokers. Histologically, LCH is characterized by a
      nodular, interstitial proliferation of Langerhans cells around the distal airways
      with associated eosinophils, lymphocytes, and macrophages. Associated findings,
      such as fibrosis, emphysematous change, and bronchiolitis can be reminiscent of
      other interstitial lung diseases. The markers CD1a and S100 have traditionally
      been used to distinguish LCH from other processes. Little is known about
      expression of the Langerhans cell-specific lectin, langerin, in pulmonary
      diseases. We examined the expression patterns of S100, CD1a, and langerin in LCH
      and other interstitial, inflammatory, and infectious processes in cases retrieved
      from the files at Brigham and Women's Hospital Department of Pathology.
      Immunoreactivity was scored according to the number of cells staining per high
      power field (400x) in areas of highest density, averaged over 4 fields. Cases
      diagnosed as LCH based on histomorphology and positive CD1a and S100 staining
      demonstrated strong langerin positivity in lesional tissue. All cases of LCH
      contained greater than 30 langerin and CD1a positive cells per high power field
      (HPF), with a mean of >100 cells per HPF, in lesional tissue. Of the other
      interstitial processes examined, only usual interstitial pneumonia demonstrated
      increased number of Langerhans cells within epithelium and interstitium (mean 14
      cells per HPF) as compared with normal lung (mean 6 cells per HPF). Langerin and
      CD1a serve as specific diagnostic markers in distinguishing LCH from other
      interstitial and inflammatory processes.

PMID- 17527086
TI  - Impact of elastic staining on the staging of peripheral lung cancers.
AB  - Accurate staging of lung cancer has a profound impact on patient management. For
      stage I nonsmall cell lung carcinomas (NSCLCs), the absence (stage IA) or
      presence (stage IB) of visceral pleural invasion represents a critical
      therapeutic branch point: patients with stage IB NSCLC benefit from adjuvant
      chemotherapy, whereas patients with stage IA NSCLC do not. Elastic staining has
      been advocated as a simple method for visualizing pleural invasion. The purpose
      of this study was to determine whether routine elastic staining of the resected
      peripheral NSCLCs alters tumor staging in a meaningful way. The study cases
      consisted of 100 consecutive peripheral NSCLCs resections that were
      pathologically staged as IA based on routine histologic assessment. Each case was
      stained with the Movats pentachrome elastic stain to aid identification of
      visceral pleural invasion. To assess current standards of surgical pathology
      practice, members of the American Association of Directors of Anatomic and
      Surgical Pathology were asked whether they never, sometimes, or always order
      elastic stains for peripheral NSCLCs that abut the pleura. Elastic staining
      resulted in a change of tumor stage from IA to IB in 19 (19%) cases. Of the 49
      pathologists that responded to the survey, 25 (51%) never, 14 (29%) sometimes,
      and 10 (20%) always order an elastic stain for NSCLCs abutting the pleura.
      Elastic staining is currently not standard surgical pathology practice for the
      evaluation of peripheral NSCLCs, but it should be. Invasion of the pleura is an
      elusive finding that is best appreciated with an elastic stain. Our experience
      suggests that routine elastic tissue staining should be performed as a standard
      method of assessing pleural involvement for pleural-based nonsmall cell lung
      carcinomas.

PMID- 17527087
TI  - Fuhrman grading is not appropriate for chromophobe renal cell carcinoma.
AB  - This study was undertaken to assess the prognostic effectiveness of Fuhrman
      nuclear grading and the individual components of this grading system, in a series
      of chromophobe renal cell carcinomas. Eighty-seven cases of chromophobe renal
      cell carcinoma were investigated. There were 47 males and 40 females, 28 to 78
      years of age. The carcinomas ranged from 25 to 180 mm in size and on TNM staging
      there were 38 stage I, 25 stage II, 22 stage III, and 2 stage IV tumors. Whole
      tumor Fuhrman grading was grade 1, 6 cases; grade 2, 72 cases; grade 3, 8 cases;
      and grade 4, 1 case, whereas focal (single high power field) grading was grade 1,
      1 case; grade 2, 62 cases; grade 3, 21 cases; and grade 4, 3 cases. On assignment
      of nucleolar grading using Fuhrman criteria there were 37 grade 1, 44 grade 2,
      and 4 grade 3 tumors on whole tumor assessment and 3 grade 1, 63 grade 2, and 21
      grade 3 tumors on assessment of the high power field showing the greatest degree
      of nuclear pleomorphism. Measurements of nuclear size showed nuclear area to
      range from 26.14 to 100.74 microm2, nuclear perimeter from 19.73 to 39.28 microm,
      and nuclear major axis from 6.49 to 13.21 microm, whereas the ranges of measures
      of nuclear shape were; shape factor 0.798 to 0.890, compactness 14.260 to 15.843,
      and feret diameter 5.694 to 11.242. Follow-up ranged from 1 to 150 months and 8
      patients died of tumor-related causes 5 to 53 months from diagnosis. On log rank
      testing against survival, only patient age (P=0.016) and tumor maximum diameter
      (P=0.0055) were significant, whereas patient sex and TNM stage were not
      significant. Whole tumor and focal Fuhrman grading, as well as all measures of
      nucleolar prominence, nuclear size, and nuclear shape showed no significant
      association with outcome. It is concluded that neither Fuhrman grading, nor any
      of the components of the Fuhrman grading system, is useful as prognostic
      indicators for this tumor type.

PMID- 17527088
TI  - Mucinous cells in type 1 pulmonary congenital cystic adenomatoid malformation as
      mucinous bronchioloalveolar carcinoma precursors.
AB  - Type 1 congenital cystic adenomatoid malformation (CCAM), the most frequent
      malformation of the lung, is the only type to present intracystic mucinous cell
      clusters, which may form beyond the cysts extracystic mucinous proliferation
      resembling mucinous bronchioloalveolar carcinomas (BACs). As mucinous BACs are
      increasingly described in the literature in young patients with CCAM, we
      hypothesized that type 1 CCAM mucinous cells could represent BAC precursors. We
      reviewed 7 cases of type 1 CCAM including 6 with intracystic mucinous cell
      clusters, 3 with extracystic mucinous proliferations, and 4 with mucinous BAC or
      mixed adenocarcinoma with predominant BAC. K-ras mutations at codon 12 were
      detected in 3/3 intracystic mucinous cell clusters, in 2/3 extracystic mucinous
      proliferations, and in 3/4 BAC. Loss of heterozygosity (LOH) at p16(INK4) locus,
      with microsatellite alterations in 3 cases, was observed in 2/3 intracystic
      mucinous cell clusters, in 2/3 extracystic mucinous proliferations, and in all
      BAC. Two extracystic mucinous proliferations showed LOH at FHIT and Rb loci,
      respectively. P16(INK4) expression was lost in 2 intracystic mucinous cell
      clusters, 1 extracystic mucinous proliferation, and 1 BAC. Neither epidermal
      growth factor receptor mutation on exons 18, 19, and 21 nor P53 accumulation was
      observed. All lesions expressed MUC5AC, but were negative for MUC2, CDX2, and TTF
      1. In conclusion, type 1 CCAM mucinous cells share the same differentiation
      profile with corresponding mucinous BAC, consistent with a common bronchial
      origin. Moreover, the high frequency of K-ras mutation and LOH and/or
      microsatellite alterations at p16(INK4) locus presented by these mucinous cells
      justifies their consideration as BAC precursors.

PMID- 17527089
TI  - Translocation and expression of CSF1 in pigmented villonodular synovitis,
      tenosynovial giant cell tumor, rheumatoid arthritis and other reactive
      synovitides.
AB  - We recently demonstrated that CSF1, the ligand of the tyrosine kinase receptor,
      CSF1R, can be translocated in pigmented villonodular synovitis (PVNS) and
      tenosynovial giant cell tumor (TGCT). In this study, we evaluated the staining
      characteristics of PVNS/TGCT and reactive synovitides for CSF1 and CSF1R by in
      situ hybridization and immunohistochemistry on tissue microarrays and correlated
      these findings with the recently described translocation. We collected specimens
      of TGCT/PVNS from 60 patients and of rheumatoid arthritis and other reactive
      synovitides from 74 patients. We identify 2 groups of PVNS and TGCT cases by the
      presence of CSF1 translocation and CSF1 expression. The first group (35 of 57
      cases; 61%) had both the CSF1 translocation and high expression of CSF1 RNA,
      confirming our previous findings. Interestingly, a second group (22 of 57 cases;
      39%) was identified that showed high expression of CSF1 RNA or CSF1 protein but
      did not have the translocation. The rheumatoid arthritis and reactive synovitis
      specimens showed localization of CSF1 RNA and protein to the synovial lining
      cells, implying a possible role for CSF1 in the pathogenesis of these lesions. As
      the CSF1 translocation is postulated to play an important role in the biology of
      PVNS/TGCT, the consistent presence of CSF1 expression in translocation-negative
      cases implies that other mechanisms can lead to CSF1 up-regulation. The
      consistent presence of CSF1 overexpression in all cases of PVNS/TGCT and reactive
      synovitides suggests both an important role for CSF1 in the spectrum of synovial
      pathologies and the possibility of targeting the CSF1/CSF1R interaction
      therapeutically.

PMID- 17527090
TI  - When to initiate HIV antiretroviral therapy: do benefits other than survival
      deserve greater attention?

PMID- 17527091
TI  - Effects of weight, body composition, and testosterone on bone mineral density in
      HIV-infected women.
AB  - Recent studies suggest that bone loss occurs among HIV-infected women. This study
      examined the effects of reduced androgen levels, changes in weight, body
      composition, and menstrual dysfunction on bone mineral density (BMD) among 152
      HIV-infected women characterized by normal weight (>90% ideal body weight [IBW],
      n = 124) and low weight (<or=90% IBW, n = 28) compared with 100 non-HIV-infected
      control subjects. BMD was assessed by dual x-ray absorptiometry, and free
      testosterone was assessed by equilibrium dialysis. Abdominal subcutaneous adipose
      tissue (SAT) and visceral adipose tissue (VAT) were determined by computed
      tomography scan. A significant difference was seen in BMD between groups at the
      lumbar spine (0.92 +/- 0.02 g/cm vs. 1.01 +/- 0.01 g/cm vs. 1.07 +/- 0.01 g/cm; P
      < 0.0001), total hip (0.84 +/- 0.03 g/cm vs. 0.94 +/- 0.01 g/cm vs. 0.98 +/- 0.01
      g/cm; P < 0.0001), and femoral neck (0.73 +/- 0.03 g/cm vs. 0.83 +/- 0.01 g/cm
      vs. 0.87 +/- 0.01 g/cm; P < 0.0001) (HIV-infected low-weight group, HIV-infected
      normal-weight group, and non-HIV-infected control subjects, respectively, for
      each comparison; mean +/- SEM). Among the HIV-infected subjects, lumbar BMD
      correlated with percent IBW (r = 0.37, P < 0.0001), total body lean mass (r =
      0.43, P < 0.0001), total body fat mass (r = 0.35, P < 0.0001), and SAT (r = 0.41,
      P < 0.0001), but not VAT (r = 0.07, P = 0.417). Clinical risk factors for
      osteopenia and osteoporosis in the HIV population identified in univariate
      analysis included low free testosterone (<1.1 pg/mL [lower limit of the normal
      range of free testosterone for women] or 3.8 pmol/L; P = 0.0007), low weight (P =
      0.014), and oligomenorrhea (P = 0.0006). In multivariate regression analysis,
      lean body mass was most significantly associated with BMD among those with HIV.
      These data demonstrate that BMD is reduced among HIV-infected women in
      association with low weight, reduced lean mass, reduced androgen levels, and
      abnormal menstrual function.

PMID- 17527092
TI  - Prevalence of and factors associated with hepatic steatosis in patients
      coinfected with hepatitis C virus and HIV: Agence Nationale pour la Recherche
      contre le SIDA et les hepatites virales CO3 Aquitaine Cohort.
AB  - BACKGROUND: Hepatic steatosis is a common feature in liver biopsies from patients
      with chronic hepatitis C and is associated with fibrosis progression. Patients
      with HIV infection and hepatitis C virus (HCV) coinfection have more rapid
      progression of liver fibrosis than patients with HCV infection alone. The
      prevalence and factors associated with hepatic steatosis are not well defined in
      HCV-HIV-coinfected patients. METHODS: Steatosis was assessed among 148 HCV-HIV
      coinfected patients of the Aquitaine Cohort. Steatosis was graded as follows:
      none, mild (1%-10% of hepatocytes), moderate (11%-30%), severe (31%-60%), and
      massive (more than 60%). Epidemiologic, clinical, biologic, and therapeutic data
      were retrieved from the cohort database to investigate the risk factors. RESULTS:
      Steatosis was present in 67% of patients (95% confidence interval [CI]: 59% to
      74%) and was at least moderate in 30% (95% CI: 23% to 38%). Steatosis was
      macrovesicular or mixed (macro- and microvesicular) in 40.5% and 52.8% of
      patients, respectively. Necroinflammatory activity was the only factor
      independent of steatosis (adjusted odds ratio = 5.3, 95% CI: 1.6 to 17.9). When
      necroinflammatory activity was removed from the model, HCV genotype 3 and body
      mass index (BMI) were significantly associated with steatosis. CONCLUSIONS: Liver
      inflammation, HCV genotype 3, and BMI are associated with steatosis, a common
      finding in HCV-HIV-coinfected patients.

PMID- 17527093
TI  - Switching to a protease inhibitor-containing, nucleoside-sparing regimen
      (lopinavir/ritonavir plus efavirenz) increases limb fat but raises serum lipid
      levels: results of a prospective randomized trial (AIDS clinical trial group
      5125s).
AB  - BACKGROUND: Subcutaneous limb fat loss continues to be one the most troubling
      side effects of long-term antiretroviral regimens. Nucleoside analogues and
      protease inhibitors (PIs) have been linked to the development of this
      complication. METHODS: We evaluated the effects of nucleoside-sparing and PI
      sparing regimens on fat distribution, bone mineral density, and metabolic
      parameters in 62 subjects, who were not selected for lipoatrophy, with advanced
      HIV (nadir CD4 count <or=200 cells/mm or HIV RNA level >or=80,000 copies/mL) and
      an undetectable HIV viral load. Participants were randomized to switch their
      initial successful antiretroviral regimen to open-label lopinavir/ritonavir
      (LPV/r) at a dose of 533/133 mg twice a day and efavirenz (EFV) at a dose of 600
      mg/d (the nucleoside-sparing arm) versus EFV and 2 nucleoside analogues (the PI
      sparing arm). FINDINGS: At week 48, the median change in limb fat in the
      nucleoside-sparing arm was 562 g (6%, interquartile range [IQR]: -218-1186 g)
      versus a loss of -242 g (-4%, IQR: -539-452 g) in the nucleoside-containing PI
      sparing arm (P = 0.086). At the time of last observation (median = 102 weeks,
      IQR: 73-152 weeks), a median gain of 782 g (10%, IQR: -380-1168 g) of limb fat
      was noted in the nonnucleoside arm (n = 22) versus a loss of 850 g (-15%, IQR: 
      1270 to -526 g) in the nucleoside-containing arm (n = 25; P = 0.002).
      INTERPRETATION: The switch to a nucleoside-sparing combination antiretroviral
      regimen (LPV/r + EFV) was associated with significant improvement in limb fat.
      These results provide additional evidence that nucleoside analogues are important
      in the progressive limb fat loss that characterizes antiretroviral treatment and
      that switching medications can significantly improve this complication. This
      option has to be carefully balanced with the potential to increase serum lipid
      levels and the trend to increase virologic failure.

PMID- 17527094
TI  - Lack of evidence for prolonged double-long terminal repeat episomal HIV DNA
      stability in vivo.

PMID- 17527095
TI  - The effect of lamivudine therapy and M184V on the antiretroviral activity of
      didanosine.

PMID- 17527096
TI  - High prevalence of primary antiretroviral resistance among HIV-1-infected adults
      and children in Bahia, a northeast state of Brazil.

PMID- 17527097
TI  - Investigating iatrogenic HIV transmission in Ugandan children.

PMID- 17527098
TI  - Response to "Factors associated with self-efficacy for condom use and sexual
      negotiation among South African youth".

PMID- 17527100
TI  - Assessment and treatment of glenohumeral joint deformities in children suffering
      from upper obstetric brachial plexus palsy.
AB  - We present our approach to gleno-humeral joint deformities as sequelae from
      severe upper obstetric brachial plexus palsy. In 50 consecutive children with
      severe medial rotation contracture of the shoulder after obstetric brachial
      plexus palsy, we used magnetic resonance imaging to evaluate joint incongruence
      and dysplasia; showing frequently various deformities of the glenoid, the humeral
      head and pathologic changes in their relationship. The most severe deformity is
      true glenohumeral dysplasia. These diagnostic findings might influence our choice
      and technical details within surgical procedures. We actually evaluate image
      processing tools (segmentation software) for a better understanding of changes in
      anatomical structures responsible for this multifactorial joint deformity,
      limiting lateral and/or medial rotation of the glenohumeral joint in children
      with obstetric brachial plexus palsy.

PMID- 17527101
TI  - Normal range of fetal finger movements.
AB  - A congenital limitation of finger movements is associated with many syndromes
      that interfere with child well-being. The normal range of fetal finger movements
      during the second and third trimester is unknown. The aim of this study was to
      measure the normal range. In this study, fetal finger flexion and extension were
      examined during routine ultrasound screening in 260 consecutive normal fetuses at
      gestational age 16-41 weeks. Full extension and flexion of the fingers were noted
      in 110 fetuses examined at 16-26 weeks. Of the 150 fetuses examined at 27-41
      weeks, full flexion and extension were noted in 118 (78.7%), full flexion and
      partial extension in 30 (20%), and full flexion without extension in two (1.3%).
      Knowledge of the normal range of fetal finger movements will assist clinicians in
      the prenatal diagnosis of other anomalies and syndromes.

PMID- 17527102
TI  - Operative treatment of developmental hip dysplasia in children aged over 8 years.
AB  - Nine patients aged over 8 years with developmental dislocation of the hip were
      treated by an open reduction, femoral shortening and varus derotation osteotomy
      with or without a Chiari osteotomy. The mean age of the patients was 11.1 years
      (range 8-17 years), and the mean follow-up period was 7.1 years (range 1-13
      years). The left hip was involved in four cases: the right in three and two cases
      were bilateral. One hip redislocated. The remaining patients recovered nearly
      full movement of the affected hip. Five out of eight patients had a normal gait
      without limping or pain. Two others limped secondary to a leg-length discrepancy,
      which was corrected with leg equalization. The remaining patient had an
      improvement of her preoperative limp and was pain-free. These results indicate
      that it is possible to obtain good hip function after open reduction of a
      developmentally dislocated hip, even after the age of 8 years.

PMID- 17527103
TI  - Ultrasonographic study of the femoropatellar joint and its attachments in normal
      infants from birth to 24 months of age: part I.
AB  - Eighty knees of 40 musculoskeletally normal infants whose age ranged from 0 to 24
      months (average 9.65 months) were ultrasonographically analyzed. The lengths of
      the patella, patellar ligament - and the Insall-Salvati index, knee being flexed
      at 30 degrees , were assessed. The angles of the femoral cartilaginous sulcus
      knee flexed at 0, 30, 60, and 90 degrees were also defined. Patellar length
      varied from 1.84 to 2.02 cm (mean, 93.3 cm; standard deviation, 0.35); patellar
      ligament length varied from 1.67 to 1.86 (mean, 1.76 cm; standard deviation,
      0.25); the Insall-Salvati index varied from 1.04 to 1.13, (mean, 1.09; standard
      deviation, 0.14); and femoral cartilaginous sulcus angle ranged from 148.7 to
      149.3 degrees (average, 148.9 degrees and standard deviation, 6.20). Statistical
      tests showed no significant difference in the proposed measures according to sex
      and side (right/left). Moreover, we did not observe significant difference in the
      femoral cartilaginous sulcus angle with respect to the various degrees of knee
      flexion. Thus, we conclude that ultrasonography is useful for determining the
      normal values of the Insall-Salvati index and femoral cartilaginous sulcus angle
      in infants from 0 to 24 months. Then, we suggest standardization of this imaging
      procedure for the early diagnosis of deformities, which might impair the knee in
      infants within this range of age.

PMID- 17527104
TI  - Ultrasonographic study of the femoro-patellar joint and its attachments in
      infants from birth to 24 months of age. Part II: children with Down syndrome.
AB  - An ultrasonographic study was carried out in 25 infants (50 knees) with Down
      syndrome, whose age ranged from zero to 24 months, average being 13.2 months; 13
      were males and 12 were females. The ultrasonographic investigation was performed
      with the knee being in full extension for the transversal view and in 30 degrees
      flexion for the sagittal view. The Insall-Salvati index and femoral cartilaginous
      sulcus angle were measured. Insall-Salvati index values ranged from 1.06 to 1.15
      (average 1.10), with standard deviation of 0.16. No significant differences were
      observed with regard to Insall-Salvati index values in normal children. The
      femoral cartilaginous sulcus angle in infants with Down syndrome ranged from
      152.7 to 155.8 degrees (average 154.3) with standard deviation of 7.959. In Down
      syndrome we noticed significant difference as compared to the normal values. The
      authors suggest that ultrasonography is useful in Down syndrome for an early
      diagnosis of instability of the patella.

PMID- 17527105
TI  - Evaluation of postoperative general quality of life for patients with
      osteosarcoma around the knee joint.
AB  - We evaluated the medium and long-term outcomes on the basis of patients' function
      and general quality of life after three different surgical procedures for
      osteosarcoma around the knee joints, that is, amputation, prosthetic
      reconstruction and rotationplasty. Twenty-six procedures in 22 patients who
      survived for at least 1 year after surgery were assessed for functional analysis
      (scores of the Musculoskeletal Tumor Society), and health-related quality of life
      assessment (SF-36) was applied to 17 patients who are alive without the disease.
      The patients treated with rotationplasty showed significantly high functional
      scores in two of six categories as compared with those undergoing the other two
      procedures. The scores of SF-36 also showed higher values for seven of eight
      subscales, however, no significant differences were observed for any subscale. We
      demonstrated that despite no statistical difference in patient self-assessment of
      outcome between the treatment modalities, there were functional benefits of
      rotationplasty over prosthetic reconstruction and amputation.

PMID- 17527106
TI  - Infantile Blount's disease treated by hemiplateau elevation and epiphyseal
      distraction using a specific external fixator: preliminary report.
AB  - The treatment of infantile Blount's disease remains controversial. The
      progressive development of epiphysiodesis of the medial tibial physis induced a
      complex deformity of the lower limb such as severe genu varum, joint incongruity,
      torsion instability and leg length discrepancy with major functional
      consequences. Nine knees on eight children (average age was 7 years and 2 months)
      were treated by a one-time procedure using a specific external fixator that
      combined elevation of the medial tibial plateau, axial correction in the valgus,
      complete sterilization of the upper tibial growth cartilage, leg lengthening
      anticipation and de-rotation if necessary. Magnetic resonance imaging was useful
      to describe the deformity and to prepare for surgery. Corrections were
      progressively obtained through the physis plan by means of short incisions and
      the use of a specific external fixator. The primary results at an average of 24
      months were good with a low rate of complications but final evaluation will be
      conducted at the end of the children's growth period.

PMID- 17527107
TI  - Achilles tendon length in children evaluated sonographically.
AB  - The purpose of this study was to improve our knowledge of the behavior of the
      Achilles tendon as a basis for decision-making in Achilles lengthening or
      tenotomy, we sonographically measured the normal and club feet of 101 babies,
      mean age 4 months, in standard parameters: tibio-talo-calcaneal angle, length of
      Achilles tendon, distance from tibia to calcaneus, and distance from a line
      parallel to the posterior cortex of the tibia to the calcaneus. All measurements
      were age-matched from birth to 1 year in maximal plantar and dorsal flexion. In
      conclusion, we describe the normal values for the four parameters in plantar and
      dorsal flexion. These can serve as a basis for decision-making in clubfoot
      management.

PMID- 17527108
TI  - Neurological classification in myelomeningocele as a spine deformity predictor.
AB  - In myelomeningocele, spinal deformities are responsible for major disability. Our
      aim was to check the predictive power for future spine deformity of a
      neurological classification applied at 5 years of age. We classified patients
      into four groups according to their neurological examination made at the age of 5
      years. Groups were defined as follows: group I, L5 or below (meaning that all the
      patients in this group have a paralysis that at least leaves the L5 segment
      intact); group II, L3-L4; group III, L1-L2; group IV, T12 and above (meaning that
      all the patients in this group have a paralysis that reaches T11 or above). One
      hundred and sixty-three patients were included. The results showed that group I
      is a predictor for the absence of spinal deformity. Group III or IV is a
      predictor for spinal deformity. Group IV is a predictor of kyphosis. It was
      previously known that the higher the neurological level, the higher the rate of
      spinal deformity at maturity, but no work had given physicians a guideline to
      assess the spinal prognosis in myelomeningocele patients. Our work showed, on the
      basis of this classification made at the age of 5 years, that future spinal
      disorders may be expected in some patients, while no spinal deformity may be
      expected in some others. Thus, an appropriate therapeutic strategy and follow-up
      can be planned.

PMID- 17527109
TI  - Botulinum toxin for the treatment of spasticity in children: attainment of
      treatment goals.
AB  - Forty patients (mean age 5 years) with a spastic disorder treated by botulinum
      injections (53 sessions) were evaluated for functional outcome in terms of
      achievement of their individual predetermined goals of treatment, rated on a
      modified Goal Attainment Scale from 1 (worsening function) to 4 (improved gross
      motor function). At the 2-week follow-up, 40% had a score of 1, 33% a score of 2,
      and 13% a score of 3; 12% showed no functional change. Botulinum treatments
      failed to significantly improve the gross motor function in this patient group.
      Treatment goals and expectations should clearly be established beforehand.

PMID- 17527110
TI  - Trevor's disease: the clinical manifestations and treatment of dysplasia
      epiphysealis hemimelica.
AB  - Trevor's disease is a rare abnormality characterized by aberrant
      osteocartilaginous growth from an epiphysis. We describe six new cases from our
      institution. A patient with isolated tibial tuberosity involvement is described
      for the first time. Each patient was classified according to Azouz into localized
      (three), classical (two) and generalized (one) form. We recommend that parents be
      counseled regarding the progressive nature of this disorder owing to the chance
      of worsening deformity with surgical excision alone, and the need to be followed
      until skeletal maturity.

PMID- 17527111
TI  - Treatment of children with cerebral palsy.

PMID- 17527112
TI  - Blog/web log - a new easy and interactive website building tool for a non-net
      savvy radiologist.
AB  - Recently, there has been no escaping the mention of blogs in the media. Blogging
      has emerged as a social phenomenon, which has impacted politics, business, and
      communication. Blogging software has enabled people with limited knowledge of the
      Internet to publish their thoughts online and participate in a global
      conversation; whereas the Blogosphere has hyperaccelerated the spread of
      information. Technorati, a blog search engine is now tracking over 7.8 million
      Weblogs, and 937 million links, and reports that there are about 30,000 to 40,000
      new blogs created a day. The majority of people who blog do so as a hobby, using
      blogs to publish their thoughts, feelings, and viewpoints on whatever topics
      interest them. Blogging software also enables people to post pictures, music, and
      more recently videos. For many people blogs are used as online journals or
      diaries; other people use blogs to communicate with their family and friends.
      Whether people generate revenue with their blogs or use them as a hobby the one
      thing they all have in common is that they are part of the Blogosphere, or
      network of blogs that gives people a voice and allows them to spread information
      at an unprecedented rate. Although searching PubMed produces few results for
      "blog" (6 relevant articles of 24), "weblog" (1 article), web log (8 entries of
      varying relevance), and "blogging" (4 articles) (none of which were in Radiology,
      RadioGraphics, AJR, or JVIR), blogging might well become an important means of
      information transfer in Radiology also. As radiology is an image-based science, a
      blog is a satisfying endeavor in that you can share your experiences with others
      instantaneously In this context, I would like to submit my experience with easy
      method for building a Web site known as blogging (maintaining a Web log). As a
      radiologist, I use my blog (http://www.sumerdoc.blogspot.com/; or
      http://www.indianradiology.com/) to post interesting cases from my routine
      practice along with any interesting abstracts I come across during my day-to-day
      work. The success of this project can be measured by the fact that in the last
      full year of "rad-blogging," more than 30,000 visitors came to the site from all
      over the world, with thousands of queries from patients, colleagues, and many
      interested students. Rad-blogging might well become a new easy method of
      information exchange and opinion building in Radiology.

PMID- 17527113
TI  - Significance of ground-glass opacity on HRCT in long-term follow-up of patients
      with systemic sclerosis.
AB  - Despite little supportive evidence, ground-glass opacity at high-resolution
      computed tomography, without other signs of fibrosis, has been equated with
      potentially reversible disease, and in systemic sclerosis, frequently prompts
      aggressive anti-inflammatory treatment to prevent pulmonary fibrosis. Our study
      evaluates ground-glass opacity on sequential high-resolution computed tomography
      in 41 patients with systemic sclerosis over a mean follow-up period of 27 months
      (r6 to 60 mo). Ground-glass opacity was the most common imaging finding, present
      in 66%, and usually associated with other signs of interstitial disease,
      including nonfibrotic interstitial opacities in 27% and fibrotic interstitial
      opacities in 32%. Improvement was only documented in 2(5%) patients with ground
      glass and nonfibrotic interstitial opacities. In systemic sclerosis, ground-glass
      opacity is most commonly associated with irreversible disease. Disease
      progression or improvement could not be predicted by the presence of ground-glass
      opacity.

PMID- 17527114
TI  - Transient interruption of contrast on CT pulmonary angiography: proof of
      mechanism.
AB  - PURPOSE: To test the hypothesis that a transient interruption of contrast is the
      result of an increase in flow of unopacified blood from the inferior vena cava
      (IVC) by comparing the relative IVC contribution to the right side of the heart
      in cases and age-matched and sex-matched controls. MATERIALS AND METHODS: This
      retrospective study was approved by our internal review board. Of 234 consecutive
      patients who had both CT pulmonary angiography and a close follow-up diagnostic
      pulmonary angiogram, or in one case CT pulmonary angiography, 7 cases were
      identified which contained a transient interruption of contrast. The study group
      included 2 men and 5 women. The age range was 37 to 77 years (mean 61.3 y +/
      13.3). The artifact consists of a segment of the pulmonary arteries which
      demonstrates poor blood enhancement between areas of increased attenuation both
      proximally and distally. Hounsfield units (HU) measurements were made in the
      areas of decreased attenuation, the areas of higher attenuation both proximally
      and distally, the superior vena cava, IVC, right atrium (RA), and right ventricle
      (RV). The relative IVC contribution was calculated by equating density in the RA
      and RV to a weighted average of the densities of the superior vena cava and IVC.
      Age-matched and sex-matched controls and a 2-tailed paired t test were used.
      RESULTS: In the patients with the artifact, the average relative IVC
      contributions to the RA and RV are 80.1% and 79.5%, respectively. In the control
      patients, the values for the RA and RV are 52.8% (P=0.02) and 55.5% (P=0.02),
      respectively. CONCLUSIONS: Transient interruption of contrast of the pulmonary
      arteries represents a flow-related phenomenon associated with an increased IVC
      contribution to the right side of the heart.

PMID- 17527115
TI  - Ventricular myocardial fat: CT findings and clinical correlates.
AB  - OBJECTIVES: Replacement of the myocardium by fat is a feature of arrythmogenic
      right ventricular dysplasia (ARVD). Pathology literature describes ventricular
      myocardial fat to be present not only in ARVD, but much more frequently related
      to aging, prior myocardial infarction (MI), and chronic ischemia. We noted focal
      ventricular myocardial fat in a group of patients who underwent chest computed
      tomography (CT) for varied indications. The aim of this study is to describe the
      noncontrast CT findings and clinical correlates of ventricular myocardial fat in
      this population. MATERIALS AND METHODS: We prospectively identified 26 patients
      whose noncontrast chest CT (5/03 to 6/04) demonstrated ventricular myocardial fat
      and whose clinical charts were available. There were 14 men and 12 women with a
      mean age of 70 years. Twenty-three percent (6/26) had prior CTs. Each CT was
      reviewed by 3 radiologists in consensus. The site of the ventricular fat was
      noted. Each patient was categorized based on the location of the fat as follows:
      group 1-right ventricle (RV) only, group 2-left ventricle (LV) only, group 3
      biventricular. Results of cardiac history, laboratory tests, and cardiac imaging
      were noted. RESULTS: The distribution of ventricular myocardial fat was: group 1
      RV-27% (7/26), group 2 LV-46% (12/26), and group 3 biventricular-27% (7/26).
      Echocardiographic, nuclear cardiology, or electrocardiographic data localizing a
      prior MI to a specific site were available in 35% (9/26) of patients: 14% (1/7)
      of group 1, 50% (6/12) of group 2, and 29% (2/7) of group 3. Myocardial fat
      corresponded to the site of MI in 89% (8/9). The presence and distribution of
      ventricular fat on CT was unchanged from prior CT in 100% (6/6). When comparing
      group 1 and group 2, group 1 was older (77 vs. 64 y, P=0.005), more often female
      (57% vs. 17%, P=0.13) and had fewer prior MI (14% vs. 50%, P=0.17) than group 2.
      Only 1 patient in this series had ARVD. He was in group 3. CONCLUSIONS: The
      significance of ventricular myocardial fat varies by location. Fat in the RV is
      most often related to aging. Prior RV MI and ARVD are less common etiologies. Fat
      in the LV is frequently related to prior MI. Recognition of myocardial fat on a
      noncontrast chest CT may be the first opportunity to diagnose a silent MI.

PMID- 17527116
TI  - MDCT of the central airways: comparison with bronchoscopy in the evaluation of
      complications of endotracheal and tracheostomy tubes.
AB  - OBJECTIVE: To evaluate the accuracy of multidetector row computed tomography
      (MDCT) compared with bronchoscopy in the assessment of airway complications
      related to endotracheal and tracheostomy tubes. MATERIALS AND METHODS: A review
      was performed of all consecutive patients undergoing computed tomography (CT) and
      bronchoscopy for symptomatic complications of endotracheal or tracheostomy tubes
      during an 18-month period. MDCT imaging was performed according to a standard
      protocol and interpreted by an experienced thoracic radiologist before
      bronchoscopy. After bronchoscopy by an experienced interventional pulmonologist,
      CT and bronchoscopic findings were reviewed jointly, and the accuracy of CT was
      determined using bronchoscopy as the "gold standard." RESULTS: The study
      population was comprised of 32 patients (range: 26 to 88 y, mean 55.6) with a
      total of 47 airway complications: tracheal stenosis (n=25), tracheomalacia (n=8),
      tracheal granulation tissue (n=8), tracheal cartilage fracture (n=4), tracheal
      perforation (n=1), and tracheostomy tube disruption (n=1). CT accurately
      diagnosed 42 of 47 airway complications (sensitivity 89.4%, specificity 95.2%,
      positive predictive value 85.7%, negative predictive value 96.5%). False negative
      findings at CT occurred in 5 (11.1%) of 47 cases. Contributing technical factors
      were identified in 3 (60.0%) of 5 false-negative cases, including the presence of
      tracheostomy tube during imaging and patient inability to complete the CT
      protocol. CONCLUSIONS: MDCT of the central airways is highly accurate for
      detecting symptomatic airway complications of endotracheal and tracheostomy
      tubes, particularly when technical limitations to the performance of CT are
      minimized.

PMID- 17527117
TI  - Pulmonary nocardiosis after lung transplantation: CT findings in 7 patients and
      review of the literature.
AB  - OBJECTIVE: The purpose of this study is to review reported radiographic clues to
      the diagnosis of pulmonary nocardiosis, as well as to describe and illustrate the
      high-resolution computed tomography findings of 7 patients with pulmonary
      nocardiosis after lung transplantation. CONCLUSIONS: Computed tomography findings
      of pulmonary nocardiosis after lung transplantation consist predominantly of
      nodules and cavitary lesions without any significant zonal or anatomic
      distribution. The diagnosis of pulmonary nocardiosis requires a high index of
      suspicion, as presenting symptoms are nonspecific, initial visualization is often
      not possible with routine stains, and identification requires prolonged cultures.

PMID- 17527118
TI  - Congenital pulmonary airway malformation: CT-pathologic correlation.
AB  - OBJECTIVES: Congenital pulmonary airway malformation (CPAM) is classified into 5
      subtypes (types 0 to 4). We attempted to correlate computed tomography (CT)
      findings with those of pathologic examination and evaluated the predictability of
      the CPAM subtype. SUBJECTS AND METHODS: We retrospectively reviewed CT findings
      in 13 pathologically proven cases of CPAM seen between 1981 and 2005. Patient's
      age ranged from 4 days to 5 years and 10 months. Six were boys and 7 were girls.
      According to CT findings, lesions with a cyst larger than 2.5 cm, lesions with
      cysts 2.5 cm or less and solid lesions were classified into groups A, B, and C,
      respectively. We assumed that Stocker's types 1 and 4, type 2, and types 0 and 3
      would correspond to CT groups A, B, and C, respectively. Then, we assessed
      whether this assumption is correct or not. RESULTS: Eight, 3, and 2 cases were
      diagnosed as groups A, B, and C, respectively. All of the 8 cases diagnosed as
      group A were Stocker's type 1. One of the 3 cases diagnosed as group B was type
      2, but the remaining 2 were type 1 and type 4, respectively. One of the 2 cases
      diagnosed as group C was type 3 but the other was type 2. CONCLUSIONS: Lesions
      with the largest cyst being larger than 2.5 cm was type 1. It seemed, however,
      difficult to distinguish among types 1, 2, and 4 when they consisted of small
      cystic components and between types 2 and 3 when they appeared as a solid lesion.

PMID- 17527119
TI  - High-resolution CT findings in patients with pulmonary tuberculosis: correlation
      with the degree of smear positivity.
AB  - BACKGROUND: There are data about the relationship between morphologic findings on
      high-resolution computed tomography (HRCT) and the number of acid-fast bacilli
      (AFB) on sputum smears in patients with pulmonary tuberculosis (PTB). It was also
      shown that existence of cavities and airspace consolidation might be related to
      smear positivity in PTB patients. However, there is no study suggesting a
      relationship between AFB on sputum smears and radiologic extent of disease based
      on HRCT findings. AIM: In this study, we investigated a relationship between the
      degree of smear positivity and radiologic extent of disease based on HRCT
      findings and, the degree of smear positivity and different pulmonary parenchymal
      changes on HRCTs of the PTB patients. METHODS: Sixty-one male patients with PTB
      (mean age: 22+/-3.2) were included into the study. HRCT images were assessed for
      patterns, distribution, and profusion of pulmonary abnormalities. Dividing the
      lungs into 3 zones, profusion of abnormalities was assessed. A profusion score
      was given. Patients were divided as smear positive and smear negative and
      compared for the scores of HRCT findings. Smear-positive patients were divided
      into 4 groups as per grading of the sputum AFB smear: group I (sputum 1+), group
      II (sputum 2+), group III (sputum 3+), and group IV (sputum 4+). Correlations
      were investigated between the degree of smear positivity and the scores of HRCT
      findings. RESULTS: A significant correlation between radiologic extent of the
      disease based on HRCT and the degree of smear positivity was found (r=0.63,
      P=0.0001). There were also significant correlations between the degree of smear
      positivity and the scores of different HRCT findings. Nodule, cavity, and
      bronchial lesions are the most important contributors of the predictive
      properties of the total score. There was significant differences for the scores
      of HRCT findings between smear-positive and smear-negative patients. CONCLUSIONS:
      Our study suggests that radiologic extent of disease based on HRCT findings in
      patients with PTB correlated with the degree of smear positivity. Different HRCT
      findings such as nodule, cavitation, ground-glass opacity, consolidation, and
      bronchial lesion are significantly associated with smear-positive PTB.
      Particularly, nodules, cavities, and bronchial lesions might be predictors of
      smear positivity in patients with PTB. This study also suggests that the
      thickness of cavity wall and the distance of cavity from central airways might be
      related to the degree of smear positivity.

PMID- 17527120
TI  - Comparison of CT features of Aspergillus and bacterial pneumonia in severely
      neutropenic patients.
AB  - PURPOSE: To establish whether a relationship exists between computed tomography
      features of lung opacities in severely neutropenic patients and their Aspergillus
      or bacterial etiology. METHODS: Computed tomography scans of 124 patients with
      lung opacities larger than 5 mm occurring during severe (neutrophils <500/mm) and
      prolonged (>7 d) neutropenia-induced by bone marrow transplantation and/or high
      dose chemotherapy for hematologic malignancies-were reviewed. Invasive pulmonary
      aspergillosis or bacterial pneumonia were assessed by means of bronchoalveolar
      lavage, bronchial washing, trans-bronchial biopsy or (for bacteria only) blood
      cultures. Pulmonary opacities were classified as nodules or as consolidations.
      The presence of a perinodular ground-glass halo, the similarity of consolidations
      to a pulmonary infarction and the presence of cavitation (crescent-shaped or not)
      were recorded. RESULTS: Invasive pulmonary aspergillosis was diagnosed in 68
      patients; bacterial pneumonia in 56. Nodules (85) were more common than
      consolidations (39); their distribution among the patients with aspergillosis (52
      nodules and 16 consolidations) and those with bacterial pneumonia (33 nodules and
      23 consolidations) was even. Out of the 19 nodules surrounded by a halo 17 were
      due to aspergillosis. Nine consolidations (3 due to aspergillosis) were
      infarctionlike shaped. Cavitation appeared during 22/68 aspergillosis and 31/56
      bacterial pneumonias; an air-crescent in 6 patients with aspergillosis and in 24
      with bacterial pneumonia. CONCLUSIONS: Although rare enough, the perinodular halo
      is highly specific for invasive aspergillosis. The nodular pattern of lung
      opacities, their similarity to a pulmonary infarction, the occurrence of
      cavitation and the air-crescent are not related to aspergillosis.

PMID- 17527121
TI  - Extralobar pulmonary sequestration with hemorrhagic infarction in an adult.
AB  - Symptomatic extralobar pulmonary sequestration in adults is thought to be
      extremely rare. We present a case of an extralobar pulmonary sequestration, with
      infarct, in a 28-year-old woman who complained abrupt onset of chest pain. Chest
      computed tomography and magnetic resonance imaging showed a mass in the left
      paraspinal area, medial to the left lower lobe, and serial chest radiographs
      revealed increasing pleural effusion. This was histopathologically confirmed to
      be a hemorrhagic infarct of the extralobar pulmonary sequestration.

PMID- 17527122
TI  - CT diagnosis of complete tracheal rings in an adult.
AB  - We report a case of complete tracheal rings diagnosed by computed tomography (CT)
      in a 34-year-old woman with history of congenital heart disease who presented
      with long-standing shortness of breath and chest tightness. CT of the trachea
      revealed concentric narrowing of the distal trachea, with an "O"-shaped lumen and
      absence of wall thickening. Virtual endoscopic CT images showed concentric rings
      at the site of stenosis, consistent with complete tracheal rings, which were
      confirmed by conventional bronchoscopy. To our knowledge, the CT findings of this
      condition have not been previously described. CT with 3-dimensional
      reconstructions has the potential to noninvasively aid in the diagnosis and
      monitoring of patients with this condition.

PMID- 17527123
TI  - Endometrioma presenting as a cavitary lung mass with intense 18F-FDG uptake on
      PET-CT.
AB  - [18F]-fluoro-2-deoxy-D-glucose positron emission tomography computed tomography
      is a useful tool to suggest the diagnosis of malignant processes. However, false
      positive results are known to occur in benign lesions that have a high metabolic
      activity. Here we describe the unusual diagnosis of a pulmonary endometrioma in a
      47-year-old woman, presenting as a cavitary lung mass with intense (18)F-FDG
      uptake on PET-CT.

PMID- 17527124
TI  - Atypical CT findings of isolated pulmonary Langerhans cell histiocytosis in a 4
      year-old boy.
AB  - A 4-year old boy was admitted to hospital with progressive respiratory failure. A
      chest roentgenogram revealed hyperinflated lungs and a diffuse reticular pattern.
      There was no smoking history in the family environment. A thin slice computed
      tomography of the lungs exhibited extended and diffuse cystic lung disease with
      no zonal predominance. An open lung biopsy showed pulmonary Langerhans cell
      histiocytosis. No other organs were involved. Despite treatment initiation the
      boy succumbed to his pulmonary insufficiency 3 weeks later. Isolated pulmonary
      Langerhans cell histiocytosis in children may have an unfavorable prognosis and
      in contrast with adults, it may present on computed tomography with lower lobe
      predominance and without sparing the lung bases or the anterior parts of middle
      lobe and lingula.

PMID- 17527125
TI  - Incidental discovery of an anterior mediastinal angiomyolipoma.
AB  - Angiomyolipomas are benign mesenchymal tumors consisting of blood vessels, smooth
      muscle, and fat. These noninvasive lesions characteristically manifest in renal
      tissue but may arise less frequently in extrarenal locations including the
      mediastinum. Only 8 cases of mediastinal angiomyolipomas have been reported in
      the literature, 3 of which were reported in the English literature, and only 2 of
      which were located in the anterior mediastinum. We report a surgically confirmed
      case of an anterior mediastinal angiomyolipoma incidentally discovered in an
      asymptomatic patient, in whom a screening breast magnetic resonance imaging
      revealed an incidental 5.7 cm anterior mediastinal mass. Further characterization
      with contrast-enhanced chest computed tomography confirmed a heterogeneously
      enhancing anterior mediastinal mass, suggestive of thymoma or lymphoma. The mass
      was resected and histopathologic evaluation revealed an angiomyolipoma.

PMID- 17527126
TI  - Pulmonary nodules associated with Gemella bacteremia: CT findings in two children
      with osteosarcoma.
AB  - Gemella morbillorum and Gemella haemolysans are normal oral flora that can also
      be pathogenic. We report 2 cases of adolescents with osteosarcoma who developed
      multiple pulmonary nodules associated with Gemella bacteremia. These nodules
      mimicked metastatic disease. To our knowledge, this manifestation of Gemella
      infection has not been previously reported. In the setting of malignancy,
      infectious pulmonary nodules must be distinguished from metastatic nodules in
      order to treat appropriately.

PMID- 17527127
TI  - Intrapericardial teratoma diagnosed on CT.
AB  - Intrapericardial teratomas are rare tumors which usually present in infancy.
      These tumors may be life-threatening because of the associated large pericardial
      effusion and cardiac compression. Here we present a case of intrapericardial
      teratoma which presented with cardiac tamponade in a neonate and was diagnosed
      using multidetector spiral computed tomography. The imaging features, clinical
      presentation, and differential diagnosis of this seldom-encountered entity are
      discussed.

PMID- 17527129
TI  - High brachiocephalic artery: CT appearance and clinical implications.
AB  - We present a case of a high brachiocephalic artery extending as far superiorly as
      the thyroid gland. Recognition of this rare anomaly is necessary to avoid
      potential catastrophic hemorrhage or other complications during percutaneous and
      surgical procedures on the trachea and neck.

PMID- 17527128
TI  - CT radiographic findings: atrio-esophageal fistula after transcatheter
      percutaneous ablation of atrial fibrillation.
AB  - INTRODUCTION: Radio-frequency catheter ablation (RFCA) is an ever increasing
      modality for treating refractory atrial fibrillation. Radiologists should not
      only be able to interpret and convey anatomic variations of pulmonary veins and
      left atrium to referring electrophysiologists, but also should be aware of all
      the post-RFCA complications and their radiographic findings including this rare,
      but often fatal complication. This report describes a fatal atrio-esophageal
      fistula (AEF) involving a normal variant single left common pulmonary vein after
      transcatheter ablation. RESULTS: A 59-year-old man who presented to the Emergency
      Department (ED) with altered mental status previously complaining of fatigue and
      malaise. The patient underwent a total of 2 uneventful circumferential
      percutaneous pulmonary vein ablations for atrial fibrillation. The most recent
      was performed 5 weeks before admission to ED. Within hours of initial evaluation,
      the patient quickly deteriorated owing to overwhelming sepsis requiring both
      inotropic and ventilatory support. Transthoracic echocardiography within ED
      showed no evidence of valvular vegetation or gas bubbles in the left atrium.
      Computed tomography (CT) of the chest with intravenous contrast revealed findings
      compatible with AEF. Head CT was negative for ischemic changes or emboli. Patient
      underwent emergent cardiac and esophageal surgery at which point the patient
      later died on the operating table. CONCLUSIONS: Patients who present with signs
      and symptoms of endocarditis, and particularly with new neurologic symptom after
      RFCA should be promptly evaluated for AEF. In our case, radiographic findings in
      correlation with clinical history and high suspicion strongly suggested this
      rare, often fatal complication. During review of the chest CT, particular
      vigilance should be made to the left pulmonary vein/posterior left atrium
      junction at which site fistulous tracts tend to occur. Prompt diagnosis
      necessitates emergent cardiac and esophageal surgery to prevent rapid
      deterioration and death.

PMID- 17527130
TI  - Metastatic shoulder liposarcoma to the right ventricle: CT findings.
AB  - Metastatic cardiac liposarcoma is rare. A right ventricular liposarcoma
      metastasis is described in a 46-year-old man, who was admitted with significant
      shortness of breath and fatigue, and in whom a large lobulated low attenuation
      mass occupying most of the right ventricular cavity, with extension through the
      right ventricular apex and a small-to-moderate pericardial effusion was detected
      by electrocardiogram-gated cardiac computed tomography. The patient had an
      antecedent history of a left upper arm liposarcoma treated with surgical
      resection, chemotherapy, and postoperative radiotherapy 3 years earlier. Surgical
      resection was performed with the majority of the neoplasm removed though; the
      right ventricular apex and epicardial extension of tumor could not be fully
      resected. The histopathologic analysis revealed a liposarcoma, similar to the one
      resected in the left arm 3 years earlier. Electrocardiogram-gated cardiac
      computed tomography was able to visualize the metastatic tumor within the heart,
      accurately evaluate cardiac function and allow for prompt surgical treatment that
      produced relief of symptoms, and assess for further metastatic disease within the
      thorax.

PMID- 17527131
TI  - Pulmonary complications of illicit drug use: differential diagnosis based on CT
      findings.
AB  - OBJECTIVE: The aim of this manuscript is to summarize an approach to the
      differential diagnosis of the pulmonary complications of illicit drug use based
      on the computed tomography findings. CONCLUSIONS: The various pulmonary
      complications of illicit drug use result in 5 main patterns of parenchymal
      abnormality: nodules, ground-glass opacities, consolidation, air trapping, and
      emphysema. Other thoracic manifestations of illicit drug use include pulmonary
      arterial hypertension, pneumomediastinum, bacterial endocarditis, discitis, and
      septic arthritis.

PMID- 17529154
TI  - Abstracts of the 54th Annual Meeting of the American College of Sports Medicine,
      May 30-June 2, 2007, New Orleans, Louisiana, USA.

PMID- 17527132
TI  - Thoracic radiographic and CT findings of multicentric Castleman disease in HIV
      infected patients.
AB  - Multicentric HIV-related Castleman disease (MCD) is a rare and severe disorder of
      lymphoid tissue inducing high-grade fever, hepatosplenomegaly, and diffuse
      peripheral lymphadenopathy. During clinical exacerbations, bilateral interstitial
      pneumonia may occur. In this pictorial essay, we describe different thoracic
      imaging of MCD, with particular emphasis on computed tomography findings, in 13
      HIV-infected patients with histologically proved MCD.

PMID- 17529847
TI  - Effect of atorvastatin on progression of sensorineural hearing loss and tinnitus
      in the elderly: results of a prospective, randomized, double-blind clinical
      trial.
AB  - OBJECTIVE: To test whether the 3-hydroxy-3-methylglutaryl- coenzyme A reductase
      inhibitor atorvastatin can slow down the progression of presbycusis. PATIENTS:
      Fifty patients 60- to 75-years-old with presbycusis and moderately elevated serum
      cholesterol. INTERVENTION(S): In a double-blind design, patients were randomly
      assigned to treatment with either atorvastatin (40 mg/d orally) or placebo. MAIN
      OUTCOME MEASURE(S): Pure-tone audiometry and tinnitus evaluation at enrolment and
      after 7 and 13 months. RESULTS: Development of hearing thresholds after 7 and 13
      months showed no significant differences between the groups. Tinnitus score
      continuously improved in the atorvastatin group (34.8 at 7 and 27.6 at 13 mo),
      whereas it slightly deteriorated in the placebo group (24.8 at 7 and 26.8 at 13
      mo). The effect on tinnitus was a tendency without statistic significance (p =
      0.0833). CONCLUSION: Atorvastatin had no effect on the development of hearing
      thresholds, but resulted in a trend toward a relief of tinnitus.

PMID- 17529848
TI  - Classroom performance and language development of CI students placed in
      mainstream elementary school.
AB  - OBJECTIVE: Investigation of the relation between classroom performance and
      language development of cochlear implant (CI) students in mainstream education.
      Structural analyses of assessment of mainstream performance (AMP) and Screening
      Instrument For Targeting Educational Risk (SIFTER) instruments. STUDY DESIGN:
      Cross-sectional instrument and language development analyses. SETTING: Tertiary
      university medical center. PATIENTS: Twenty-six CI children in elementary school
      with congenital or prelingual deafness were included. At the time of this study,
      mean period of multichannel CI use was 5.3 years, and children's ages ranged from
      6.5 to 12.8 years. MAIN OUTCOME MEASURE: Assessment of mainstream performance and
      SIFTER instruments measured classroom performance and language development were
      measured by means of Reynell and Schlichting tests. RESULTS: Assessment of
      mainstream performance and SIFTER domains showed good reliability (Cronbach alpha
      >0.6), but factor analyses only showed the expected instrument structure in the
      AMP. In both questionnaires and within all domains, individual variability is
      detected. Spearman's correlation analyses showed the probable explanation of
      individual questionnaire variability by language test results (p value mostly
      <0.01). The AMP and SIFTER instruments showed a predictive capacity for language
      development, based upon general linear model univariate and linear regression
      analyses. CONCLUSION: Individual classroom performance, measured by AMP and
      SIFTER questionnaires, of CI children in mainstream education varies. Correlation
      analyses showed strong significant relation between questionnaire results
      (classroom performance) and both expressive and receptive language test results
      (Schlichting and Reynell tests). Structural questionnaire analyses of the AMP and
      SIFTER demonstrated good reliability. The predictive value of the AMP can monitor
      the actual linguistic functioning of the child.

PMID- 17529849
TI  - Hybrid cochlear implantation: clinical results and critical review in 13 cases.
AB  - OBJECTIVE: To substantiate the benefits of hybrid cochlear implantation (CI) in
      patients with residual low-frequency hearing. STUDY DESIGN: Prospective study of
      patients in a manufacturer-sponsored clinical trial. SETTING: Independent
      referral center for CI. PATIENTS: Thirteen patients who met candidacy criteria
      for a hybrid CI. The 10 women and 3 men had a mean age of 51 years. INTERVENTION:
      Preoperative evaluation, CI with a Nucleus Hybrid cochlear implant, subsequent
      programming, and diagnostic testing. MAIN OUTCOME MEASURES: Benefits of high
      frequency electrical stimulation from the hybrid CI as measured by conventional
      audiometry, consonant-nucleus-consonant monosyllabic word and Bamford-Kowal-Bench
      sentence in noise testing at quarterly intervals per protocol. RESULTS: Follow-up
      ranged from 3 to 24 months. All 13 patients had preserved hearing immediately
      postoperative. However, one lost residual hearing 7 days postoperatively, and 2
      patients had delayed hearing losses at 2 and 24 months, the latter apparently due
      to barotrauma; however, this was not conclusive. Another had a bilateral
      symmetrically progressive hearing loss. Six patients showed changes in low
      frequency hearing less than 10 dB; 2 showed changes in the range 11 to 20 dB; 2,
      21 to 30 dB; and 3, more than 50 dB. Eleven of 13 had improved consonant-nucleus
      consonant words ranging up to 83% when tested with hearing aid + CI in the
      operated ear. Four subjects exhibited improvement in Bamford-Kowal-Bench sentence
      in noise testing, although only one subject showed a significant decline
      associated with bilateral progression in hearing impairment. CONCLUSION: Combined
      electrical and acoustical hearing can result in significant improvement in speech
      understanding. Only one patient lost residual hearing as a direct result of
      surgery. Two others had delayed losses. There are no absolute predictive factors
      as to success with hybrid CI, just as there are none for conventional CI.
      Similarly, wide variation in results may occur. Further studies may clarify
      factors involved in such variation.

PMID- 17529850
TI  - Distribution of different collagen types in the rat's tympanic membrane and its
      suspending structures.
AB  - BACKGROUND: The objective of the study was to investigate the histological
      distribution of collagens in the healthy rat's tympanic membrane. METHODS:
      Immunohistochemical analysis of collagen type I, II, III, and IV in the tympanic
      membranes in healthy adult female Sprague-Dawley rats. The staining was
      semiquantified using light microscopy in a blinded fashion, not knowing what type
      of collagen the slide had been stained for. RESULTS: The pars tensa of the
      tympanic membrane was mainly stained for collagen type II and IV. The fibrous
      annulus could on immunohistochemistry be subdivided into an inner and an outer
      portion. The inner portion of the fibrous annulus was mainly stained for collagen
      type II, whereas the outer portion was most strongly stained for collagen type
      III and collagen type IV. The test-retest reliability of the semiquantative
      method was 81%. CONCLUSION: Collagen type II and IV are the major collagen
      constituents of the pars tensa of the tympanic membrane. The outer portion of the
      fibrous annulus has collagen type III and IV as its major constituents, whereas
      the inner portion is made up of collagen type II.

PMID- 17529851
TI  - Hydroxyapatite versus titanium ossiculoplasty.
AB  - OBJECTIVE: To compare the results of ossicular chain reconstruction using
      hydroxyapatite (HA) and titanium (TI) prostheses. STUDY DESIGN: Retrospective
      study and case series. SETTING: Tertiary referral center. PATIENTS: One hundred
      sixty-eight patients presenting chronic otitis media with or without
      cholesteatoma. INTERVENTION: Ossiculoplasty using partial or total HA and TI
      ossicular replacement prostheses (TORP and PORP, respectively). MAIN OUTCOME
      MEASURES: Patients were assessed at 2 months postoperatively to establish short
      term results. Results of treatment for conductive hearing loss were reported
      according to guidelines. Available audiometric data at 1, 2, 3, and 5 years were
      used to assess prosthesis stability. Average postoperative air-conduction gain,
      air-bone gap, and sensorineural hearing level were measured at four frequencies:
      0.5, 1, 2, and 4 kHz. Statistical analyses compared outcomes for HA TORP versus
      TI TORP and HA PORP versus TI PORP. RESULTS: Postoperative air-bone gap of less
      than 20 dB was obtained in 50% of HA TORP versus 45.8% of TI TORP cases and in
      63.2% of HA PORP versus 72% of TI PORP cases. Preoperative middle ear status and
      presence/absence of malleus significantly influenced postoperative audiometric
      results. All types of prosthesis demonstrated significant postoperative air
      conduction gain decrease on follow-up. Prosthesis exclusion was observed in three
      cases (1.78%). CONCLUSION: Prostheses using both types of biomaterial gave good
      functional results and stability with low exclusion rates, with no statistically
      significant differences between the two. Trends could be observed for slightly
      better results for HA in total reconstruction and for TI in partial
      reconstruction. The degradation in postoperative functional gain seemed to be
      independent of prosthesis type.

PMID- 17529852
TI  - Tympanic membrane breakdown after intratympanic injection of steroids in
      irradiated ears.
AB  - OBJECTIVE: To describe a rare complication of intratympanic injection of steroids
      in susceptible ears. PATIENTS: We present two patients with a history of
      irradiation involving the injected ear. INTERVENTION: Therapeutic. MAIN OUTCOME
      MEASURE: Tympanic membrane condition after intratympanic injection of steroids.
      RESULTS: Total or near-total breakdown of the irradiated tympanic membrane.
      CONCLUSION: Tympanic membranes with an impaired wound-healing ability, together
      with exposure to intratympanic steroids, may be at risk for total or near-total
      breakdown.

PMID- 17529853
TI  - Clinical use of subjective visual horizontal and vertical in patients of
      unilateral vestibular neuritis.
AB  - OBJECTIVES: Subjective visual horizontal (SVH) and subjective visual vertical
      (SVV) used to assess otolith dysfunction and ipsilesional deviation of SVV and
      SVH in unilateral vestibular dysfunction is well known. The goal of this study
      was to investigate the clinical use of SVH/SVV and a dizziness scale in the
      clinical setting of acute unilateral vestibular neuritis. METHODS: Thirty-five
      patients with unilateral vestibular neuritis were investigated. Every patient was
      diagnosed by physical examination and electronystagmography. Subjective visual
      horizontal and SVV were assessed during the acute or subacute period; the
      Dizziness Handicap Inventory (DHI) and Vestibular Disorder Activities of Daily
      Living Scale (VADL) were used for a self-dizziness scale at the same time. All
      patients underwent rehabilitation therapy. Subjective visual horizontal/SVV and
      DHI/VADL were assessed again approximately 4 weeks later. Postrehabilitation
      SVH/SVV and DHI/VADL data were compared with initial data. RESULTS: Dizziness
      Handicap Inventory and VADL were improved after 4 weeks of rehabilitation, and
      the deviation toward ipsilesional side SVH and SVV was also improved. CONCLUSION:
      These results demonstrate that SVH and SVV correlated with clinical dizziness
      symptoms in patients with acute unilateral vestibular neuritis. Therefore, SVH
      and SVV would be useful tools for the evaluation of clinical manifestations of
      unilateral vestibular neuritis.

PMID- 17529854
TI  - Intraoperative monitoring of hearing during cerebellopontine angle tumor surgery
      using transtympanic electrocochleography.
AB  - OBJECTIVE: To investigate the use of transtympanic electrocochleography (TT
      ECochG) analyzed on-line by a detector strategy software that made possible
      automatic extraction of TT-ECochG components intraoperatively in real-time
      domain. PATIENTS: Fifteen patients with cerebellopontine angle tumor among 50
      patients were included in this study. INTERVENTION: All subjects were operated on
      via middle fossa or retrosigmoid approach. Pure-tone average (PTA) was measured
      at 0.5, 1.0, and 2.0 kHz, and calculations were performed before and after
      surgery. Auditory function was monitored intraoperatively via TT-ECochG, and
      analyzed data were displayed on-line. MAIN OUTCOME MEASURES: TT-ECochG changes in
      morphology were described. Postoperative PTA elevation level correlated with TT
      ECochG morphology changes occurring intraoperatively. RESULTS: Analyzed on-line,
      TT-ECochG data were displayed as first negative peak of compound action potential
      amplitude and latency in time domain every 3 to 5 seconds. A good correlation
      between postoperative PTA elevation and TT-ECochG morphology changes was showed
      (Spearman rank test, R = +0.93; t(N-2) = 9.00; p < 0.0001). CONCLUSION: TT-EcochG
      seemed to effectively mirror even minimal changes in auditory function during
      intraoperative monitoring in real-time domain. Developed strategy of on-line
      analysis makes the intraoperative hearing status assessment faster and easier.

PMID- 17529855
TI  - Tympanometry and laser Doppler interferometry measurements on otitis media with
      effusion model in human temporal bones.
AB  - HYPOTHESIS: The aim of this study is to investigate the effect of middle ear
      fluid and pressure on tympanic membrane mobility by using laser Doppler
      interferometry and to compare these results with tympanometry. BACKGROUND:
      Tympanometry has been commonly used for evaluation of otitis media with effusion,
      a middle ear disease with fluid in the cavity. However, this test lacks specific
      interpretations of middle ear disorders based on tympanometric data. Laser
      interferometry, as an advanced research tool to measure middle ear function, may
      provide knowledge of how tympanic membrane mobility is affected by middle ear
      fluid and pressure. METHODS: An otitis media with effusion model was created in
      seven human temporal bones for conducting experiments with tympanometry and laser
      interferometry. Middle ear pressure varied from -20 to +20 cm water, and the
      amount of fluid in the middle ear was gradually increased to fill the cavity.
      RESULTS: The displacement of the tympanic membrane measured by laser
      interferometry at selected frequencies decreased significantly corresponding to
      the middle ear air pressure changes. Tympanometry detected middle ear pressure by
      the change of tympanometric peak location, but the tympanogram shape was not
      affected by the middle ear pressure. The middle ear fluid was detected by
      tympanometry with as little as 0.3 mL, and laser interferometry was able to
      measure the displacement change of the tympanic membrane with 0.2 or 0.3 mL fluid
      at different frequencies. CONCLUSION: Laser interferometry can detect the effect
      of middle ear pressure and fluid on tympanic membrane movement as well as
      tympanometry does.

PMID- 17529856
TI  - Protective effect of methylprednisolone on the chicken's cochlea (basilar
      papilla) during and after exposure to wideband noise.

PMID- 17529857
TI  - Hildanus' specula.

PMID- 17529859
TI  - Impact of the pneumococcal conjugate vaccine on serotype distribution and
      antimicrobial resistance of invasive Streptococcus pneumoniae isolates in Dallas,
      TX, children from 1999 through 2005.
AB  - BACKGROUND: Because the heptavalent pneumococcal conjugate vaccine has reduced
      vaccine-type invasive pneumococcal disease (IPD) in children, a greater
      proportion of IPD is now caused by nonvaccine (NVT) serotypes. We analyzed the
      serotypes, antimicrobial resistance profiles and genetic relatedness of
      Streptococcus pneumoniae responsible for IPD at Children's Medical Center of
      Dallas. METHODS: S. pneumoniae isolates were collected from January 1, 1999
      through December 31, 2005. Incidence of IPD was calculated using inpatient and
      emergency center admissions to Children's Medical Center of Dallas as the
      denominator. Isolates were serotyped, and their penicillin and cefotaxime
      susceptibility determined. The 19A isolates were further characterized by pulsed
      field gel electrophoresis, multilocus sequence typing and determination of
      penicillin-binding proteins and mef and erm genes. RESULTS: The incidence of IPD
      decreased from 93.6 cases/100,000 patients in 1999 to a nadir of 41 cases/100,000
      patients in 2003 (P < 0.001). The number of IPD cases caused by serotype 19A
      increased, accounting for 40% of the cases of IPD in 2005. Penicillin and
      cefotaxime susceptibility of IPD isolates did not change from 1999 through 2005
      (P = 0.687). There was a decrease in penicillin (P < 0.001) and cefotaxime (P =
      0.034) susceptibility in NVT serotypes from 1999 to 2005. Molecular
      characterization of 19A isolates revealed a predominance of ST-199 (62%). Several
      highly penicillin-resistant and intermediately cefotaxime-resistant strains
      emerged in 2004 and 2005. CONCLUSIONS: In Dallas, heptavalent pneumococcal
      conjugate vaccine reduced the incidence of IPD from 1999 to 2005 by reducing the
      incidence of vaccine-type disease. NVT serotypes, particularly 19A, were
      prevalent and more resistant to antimicrobials in 2004 and 2005.

PMID- 17529860
TI  - Emergence of 19A as virulent and multidrug resistant Pneumococcus in
      Massachusetts following universal immunization of infants with pneumococcal
      conjugate vaccine.
AB  - BACKGROUND: The long-term effects of selective pressure from conjugate
      pneumococcal vaccine on the serotype distribution and antimicrobial resistance of
      carriage and invasive isolates of Streptococcus pneumoniae are unknown. Early
      changes demonstrate a reduction in vaccine serotypes and an increase in
      nonvaccine serotypes (NVT) among both carriage and invasive isolates. Ongoing
      surveillance is necessary to identify emerging invasive serotypes and
      antimicrobial susceptibilities. METHODS: Enhanced surveillance of invasive
      pneumococcal disease in Massachusetts began in October 2001 and remains ongoing.
      Isolates from children less than 5 are sent to the Massachusetts Department of
      Public Health and subsequently to the Maxwell Finland laboratory for serotyping
      and determination of antimicrobial susceptibility. Annual incidence rates for
      vaccine serotype and NVT disease are calculated using 2000 census data. RESULTS:
      NVT caused 72%-91% of invasive pneumococcal disease annually in children less
      than 5 years of age between 2002 and 2005. Serotype 19A has emerged as the most
      frequent cause of IPD in Massachusetts. A multidrug-resistant clone (ceftriaxone,
      amoxicillin, azithromycin and trimethoprim-sulfamethoxazole) (MLST 320) was first
      identified in Massachusetts in 2005. CONCLUSIONS: Three years after the
      introduction of pneumococcal conjugate vaccine for universal administration to
      children less than 2 in Massachusetts, a significant increase in invasive disease
      due to serotype 19A was observed. Although MLST 199 remains the most frequent
      sequence type among invasive isolates (of 19A), a multidrug-resistant sequence
      type, not previously identified in Massachusetts, has become an important cause
      of invasive disease. Further surveillance of the changing ecology of S.
      pneumoniae is necessary as a 4-year time period is not sufficient to fully
      evaluate the impact of PCV of pneumococcal infections.

PMID- 17529861
TI  - Resurgence of the multiresistant pneumococcus in the United States: a commentary.

PMID- 17529862
TI  - Human monocytic ehrlichiosis in children.
AB  - BACKGROUND: Human monocytic ehrlichiosis (HME) is a tick-borne illness caused by
      Ehrlichia chaffeensis. Data about disease in children have been largely derived
      from case reports or small case series. METHODS: A retrospective review of all
      medical and laboratory records from 6 sites located in the "tick belt" of the
      Southeastern United States was carried out. Demographic, history and laboratory
      data were abstracted from the identified medical records of patients. Bivariate
      statistical comparisons were performed using Fisher exact test or Wilcoxon rank
      sum tests. RESULTS: Common clinical signs and symptoms of patients with HME (n =
      32) included fever (100%), headache (69%), myalgia (69%), rash (66%),
      nausea/vomiting (56%), altered mental status (50%) and lymphadenopathy (47%).
      Only 48% had a complaint of fever, headache and rash. Common laboratory
      abnormalities included thrombocytopenia (94%), elevated aspartate
      aminotransferase (90%), elevated alanine aminotransferase (74%), hypoalbuminemia
      (65%), lymphopenia (57%), leukopenia (56%) and hyponatremia (55%). The median
      number of days of illness before the initiation of antirickettsial therapy was 6.
      Patients who received sulfonamides before starting doxycycline therapy developed
      a rash, were admitted to the hospital, and started doxycycline at a later date.
      Twenty-two percent of patients were admitted to the intensive care unit with
      12.5% of patients requiring ventilatory and blood pressure support. CONCLUSIONS:
      Although HME has been recognized among children for almost 20 years, there is
      only a limited knowledge about its clinical course. Even among physicians
      practicing in endemic regions, few cases are diagnosed each year. More work is
      needed to understand the true burden of disease and the natural history among
      asymptomatically and symptomatically infected children.

PMID- 17529863
TI  - Recurrent systemic pneumococcal disease in children.
AB  - BACKGROUND: Recurrent systemic pneumococcal infection usually occurs in
      immunocompromised patients and patients with underlying conditions. METHODS:
      Between 1993 and 2006, investigators at 8 pediatric hospitals prospectively
      identified cases of invasive pneumococcal disease (IPD) and retrospectively
      documented demographics and clinical information. Antibiotic susceptibility was
      determined for penicillin and ceftriaxone by microbroth dilution. Isolates were
      serotyped and molecular relatedness determined using pulse field gel
      electrophoresis (PFGE). RESULTS: Four thousand sixty-seven children were
      diagnosed with IPD over 12.3 years. One hundred and 8 episodes of recurrent
      disease were seen in 90 children (2.6%); 75 experienced 2 infections, 12
      experienced 3 infections and 3 experienced 4 infections. Fourteen of the 15
      children with >2 episodes of infection had underlying conditions. The mean
      duration between 1st and 2nd infection was 22.9 weeks for children with no known
      underlying condition and 43.0 weeks for children with an underlying condition (P
      = 0.001). Seventy episodes of IPD among the 90 patients were caused by a
      different serotype or a different genotype as demonstrated by the PFGE. Sixteen
      children had intervals <30 days between infections; 7 were caused by different
      strains. CONCLUSIONS: Approximately 80% of the children with recurrent invasive
      pneumococcal disease had underlying conditions. Seven of 16 children with
      recurrent infection <30 days apart were caused by acquisition of a new strain.
      Relapse of infection requires documentation that the pneumococcal isolates are
      not only the same serotype but also have the same PFGE patterns.

PMID- 17529864
TI  - Hospitalized children with respiratory syncytial virus infection and
      neuromuscular impairment face an increased risk of a complicated course.
AB  - BACKGROUND: Respiratory syncytial virus (RSV) infection is an important cause of
      viral respiratory tract infection in children. In contrast to other confirmed
      risk factors that predispose to a higher morbidity and mortality, the particular
      risk of a preexisting neuromuscular impairment (NMI) in hospitalized children
      with RSV infection has not been prospectively studied in a multicenter trial.
      METHODS: The DMS RSV Paed database was designed for the prospective multicenter
      documentation and analysis of all clinically relevant aspects of the management
      of inpatients with RSV infection. Patients with clinically relevant NMI were
      identified according to the specific comments of the attending physicians and
      compared with those without NMI. RESULTS: This study covers 6 consecutive
      seasons; the surveillance took place in 14 pediatric hospitals in Germany from
      1999 to 2005. In total, 1568 RSV infections were prospectively documented in 1541
      pediatric patients. Of these, 73 (4.7%) patients displayed a clinically relevant
      NMI; 41 (56%) NMI patients had at least 1 additional risk factor for a severe
      course of the infection (multiple risk factors in some patients; prematurity in
      30, congenital heart disease in 19, chronic lung disease 6 and immunodeficiency
      in 8). Median age at diagnosis was higher in NMI patients (14 vs. 5 months); NMI
      patients had a greater risk of seizures (15.1% vs. 1.6%), and a higher proportion
      in the NMI group had to be mechanically ventilated (9.6% vs. 1.9%). Eventually,
      the attributable mortality was significantly higher in the NMI group (5.5% vs.
      0.2%; P < 0.001 for all). Multivariate logistic regression confirmed that NMI was
      independently associated with pediatric intensive care unit (PICU) admission (OR,
      4.94; 95% CI, 2.69-8.94; P < 0.001] and mechanical ventilation (OR, 3.85; 95% CI,
      1.28-10.22; P = 0.017). CONCLUSION: This is the first prospective multicenter
      study confirming the hypothesis that children with clinically relevant NMI face
      an increased risk for severe RSV-disease. It seems reasonable to include NMI as a
      cofactor into the decision algorithm of passive immunization.

PMID- 17529865
TI  - Safety and effect of chlorhexidine skin cleansing on skin flora of neonates in
      Bangladesh.
AB  - BACKGROUND: Chlorhexidine cleansing of newborn skin is a highly promising
      intervention for reducing neonatal mortality in developing countries, yet little
      is known of the mechanism of action. This study examined the impact of a single
      skin cleansing of hospitalized newborn infants in Bangladesh with baby wipes
      containing 0.25% chlorhexidine on both qualitative and quantitative skin flora.
      METHODS: Within 72 hours of birth, the skin of newborns admitted to Dhaka Shishu
      Hospital was wiped with baby wipes containing 0.25% chlorhexidine (n = 67) or
      placebo (n = 66) solution. Skin condition was assessed and skin swabs were taken
      from 3 sites (axillary, peri-umbilical, inguinal) at baseline and 2 hours, 24
      hours, 3 days and 7 days after treatment. Skin flora was quantified and
      colonizing species were identified. FINDINGS: Skin cleansing with chlorhexidine
      had no adverse effects on skin condition, and resulted in minimal reduction (mean
      0.5 degrees C) in body temperature. Positive skin culture rates 2 hours after
      skin cleansing were approximately 35%-55% lower than the baseline rates for
      placebo and chlorhexidine groups at all 3 sites. For the chlorhexidine group,
      positive skin culture rates remained significantly lower than the baseline rates
      for 24 hours to 3 days, whereas for the placebo group, beyond the first 2-hour
      follow-up, these values were not lower than baseline in any of the 3 sites.
      INTERPRETATION: Chlorhexidine skin treatment produced more extended skin
      cleansing effects than the placebo treatment. It is possible that the
      quantitative and qualitative reductions observed in the skin flora might
      contribute to reducing neonatal infections.

PMID- 17529866
TI  - Use of combination vaccines is associated with improved coverage rates.
AB  - BACKGROUND: The number of shots represented by the routine childhood immunization
      schedule poses a logistical challenge for providers and a potential deterrent for
      parents. By reducing the number of injections, use of combination vaccines could
      lead to fewer deferred doses and improved coverage rates. OBJECTIVE: To determine
      the effect of combination vaccines on coverage rates. METHODS: This was a
      retrospective study of administrative claims data from the Georgia Department of
      Community Health Medicaid program conducted from January through September of
      2003. Coverage rates were compared between children who received at least 1 dose
      of HepB/Hib (COMVAX) or DTaP/HepB/IPV (PEDIARIX) (the combination cohort) and
      children who received no doses of either combination (the reference cohort).
      Infants with fewer than 4 vaccination visits were excluded from the analysis.
      Multivariate logistic regression was performed on the whole study population to
      assess the effect of combination vaccines while controlling for potential
      confounders. Hepatitis B and pneumococcal conjugate vaccine coverage rates were
      not included as outcomes. RESULTS: The study population consisted of 18,821
      infants, 16,007 in the combination cohort and 2814 in the reference cohort.
      Unadjusted coverage rates for DTaP, IPV and the 4 DTaP:3 IPV:1 MMR, 4 DTaP: 3
      IPV: 1 MMR: 3 Hib: 1 varicella, and 3 DTaP:3 IPV: 3 Hib series were higher in the
      combination cohort. Receipt of at least 1 dose of a combination vaccine was
      independently associated with increased coverage for each of these vaccines and
      vaccine series when controlling for gender, birth quarter, race, rural versus
      urban residence and historical provider immunization quality. CONCLUSIONS: Use of
      combination vaccines in this Medicaid population was associated with improved
      coverage rates. Additional studies are warranted, including those examining
      private sector populations and outcomes such as timeliness and cost.

PMID- 17529867
TI  - Determination of extended-interval gentamicin dosing for neonatal patients in
      developing countries.
AB  - BACKGROUND: Infectious diseases account for an estimated 36% of neonatal deaths
      globally. The purpose of this study was to determine safe, effective, simplified
      dosing regimens of gentamicin for treatment of neonatal sepsis in developing
      countries. METHODS: Neonates with suspected sepsis in the neonatal intensive care
      unit (NICU) at Christian Medical College and Hospital (CMC), Vellore, India (n =
      49), and Dhaka Shishu Hospital (DSH), Bangladesh (n = 59), were administered
      gentamicin intravenously according to the following regimens: (1) 10 mg every 48
      hours for neonates <2000 g; (2) 10 mg every 24 hours for neonates 2000-2249 g;
      and (3) 13.5 mg every 24 hours for neonates > or =2500 g. Serum gentamicin
      concentration (SGC) at steady state and pharmacokinetic indices were determined.
      Renal function was followed while under treatment and hearing was examined 6
      weeks to 3 months after discharge. RESULTS: All neonates, except 1 weighing 2000
      2249 g at DSH, had a peak SGC >4 microg/mL. Overall, 5 (10%) and 17 (29%) infants
      had a peak SGC level > or =12 microg/mL from CMC and DSH, respectively, and 10
      (20%) and 4 (7%) cases from CMC and DSH, respectively, had a trough SGC level >
      or =2 microg/mL. However, no infant <2000 g had a trough SGC level > or =2
      microg/mL. We found no evidence of gentamicin nephrotoxicity or ototoxicity.
      CONCLUSION: Safe, therapeutic gentamicin dosing regimens were identified for
      treatment of neonatal sepsis in developing country settings. Administration of
      these doses could be simplified through use of Uniject, a prefilled, single
      injection device designed to make injections safe and easy to deliver in
      developing country settings.

PMID- 17529868
TI  - Bloodstream infection caused by Stenotrophomonas maltophilia in children.
AB  - BACKGROUND: Stenotrophomonas maltophilia, a multidrug resistant Gram-negative
      pathogen, has become a more frequent cause of bloodstream infections (BSI).
      Little is known about development of S. maltophilia bacteremia in children. The
      objective of this study was to define risk factors and outcomes associated with
      S. maltophilia BSI in children. METHODS: This was a retrospective case-control
      study conducted at The Children's Hospital of Philadelphia between January 1,
      2000 and July 31, 2005. All patients with S. maltophilia BSI were compared with a
      random sample of patients with non-Stenotrophomonas Gram-negative rod BSI.
      RESULTS: Fifty-one cases and 103 control subjects were included in the study. The
      median patient age was 2 years (interquartile range: 1 day-8.5 years). Patients
      with S. maltophilia BSI were significantly more likely to have a malignancy and
      be coinfected with other organisms than those with other Gram-negative rod
      infections. On multivariate analysis, patients with S. maltophilia BSI were more
      likely to develop their infection in the home setting (adjusted OR, 4.18; 95% CI:
      1.44-12.16; P = 0.009). Additionally, prior exposure to trimethoprim
      sulfamethoxazole, receipt of steroids or other immunosuppressive medication in
      the 30 days preceding infection and black race were associated with the
      development of S. maltophilia BSI. CONCLUSIONS: Patients with Stenotrophomonas
      maltophilia BSI are more likely to have a polymicrobial infection and develop
      their infection in the home setting compared with patients with BSI caused by
      other Gram-negative rods.

PMID- 17529869
TI  - Analysis of the cause of increased measles incidence in Xinjiang, China in 2004.
AB  - BACKGROUND: Increased number of measles cases were reported from Xinjiang
      province of China in 2004, relative to previous years. This study aimed to
      identify the direct cause for this increase in measles morbidity and the major
      reason for the relatively high measles incidence rate in Xinjiang. METHODS: The
      epidemiologic and laboratory surveillance data for measles cases of 2004 were
      analyzed and a seroepidemiologic investigation involving 1024 subjects, mainly
      children aged less than 15 years, was conducted in Xinjiang. A questionnaire
      including demographic and vaccination data was completed by interview and blood
      samples drawn from surveillance subjects. Sera were analyzed for measles IgM
      (cases) and IgG (cases and surveillance). Data were assessed for their
      relationship with high measles incidence rate. RESULTS: 6271 measles cases were
      reported from Xinjiang in 2004 with a morbidity of 33.7 cases per 100,000
      population. 83% of the cases were children less than 12-year-old. 50% of the
      serum samples were measles IgM positive and 69% were measles IgG positive. 2014
      serum samples were collected in the seroepidemiologic survey. The overall IgG
      antibody seropositivity rate was 89%, preschool children having the lowest
      seropositivity rate (86%). There was a significant difference in IgG positive
      rates as well as IgG titers between unvaccinated and vaccinated subjects with
      each subsequent dose leading to further increase in titer. CONCLUSIONS: Low
      routine measles vaccine coverage was the major probable cause contributing to the
      increased measles cases in 2004 in Xinjiang and the high measles infection rate
      overall. The national 2-dose measles vaccination regimen is effective if
      delivered appropriately.

PMID- 17529870
TI  - Child mortality according to maternal and infant HIV status in Zimbabwe.
AB  - BACKGROUND: HIV causes substantial mortality among African children but there is
      limited data on how this is influenced by maternal or infant infection status and
      timing. METHODS: Children enrolled in the ZVITAMBO trial were divided into 5
      groups: those born to HIV-negative mothers (NE, n = 9510), those born to HIV
      positive mothers but noninfected (NI, n = 3135), those infected in utero (IU, n =
      381), those infected intrapartum (IP, n = 508), and those infected postnatally
      (PN, n = 258). Their mortality was estimated. RESULTS: Two-year mortality was
      2.9% (NE infants), 9.2% (NI), 67.5% (IU), 65.1% (IP), and 33.2% (PN). Between 8
      weeks and 6 months, mortality in IU infants quintupled (from 309 to 1686/1000 c
      y). The median time from infection to death was 208, 380, and >500 days for IU,
      IP, and PN infants, respectively. Among NI children, advanced maternal disease
      was predictive of mortality. Acute respiratory infection was the major cause of
      death. CONCLUSIONS: Perinatally infected infants are at particular risk of death
      between 2 and 6 months: cotrimoxazole prophylaxis and early pediatric HAART
      should be scaled up. Uninfected infants of infected mothers have at least twice
      the mortality risk of infants born to uninfected mothers: all HIV-exposed infants
      should be targeted with child survival interventions. HIV-positive mothers with
      more advanced disease are not only more likely to infect their infants, but their
      infants are more likely to die, whether infected or not: provision of
      antiretroviral treatment to pregnant and lactating women is an urgent need for
      both mothers and their children.

PMID- 17529871
TI  - Use of molecular typing in infection control.

PMID- 17529873
TI  - A review of antimicrobial control strategies in hospitalized and ambulatory
      pediatric populations.
AB  - Antimicrobial resistance is a growing crisis in healthcare. Various antimicrobial
      stewardship strategies have been used to control antibiotic use in efforts to
      reduce antibiotic resistance. We conducted a systematic review of antimicrobial
      stewardship programs in pediatric settings. Twenty-eight published studies met
      inclusion criteria. The majority (21 of 28) of studies had positive outcomes, but
      only 6 measured the impact of interventions on antimicrobial resistance.
      Prescriber education for a specific diagnosis (eg, otitis media) was the most
      effective intervention in the outpatient setting. Ancillary laboratory tests (eg,
      rapid diagnostic assays for viral pathogens) were most effective in the inpatient
      setting. Most studies had moderate to high risk of bias, mainly because of
      selection bias, inadequate preintervention data for time series analysis, and
      contamination between treatment groups. To date, there are a limited number of
      studies assessing antimicrobial stewardship in pediatric settings and these have
      heterogeneous study designs. Thus, it is difficult to determine the most
      effective interventions. Future studies should be designed to overcome the biases
      encountered in current publications.

PMID- 17529874
TI  - Antibiotic stewardship in pediatrics: a necessity.

PMID- 17529875
TI  - Effectiveness of pneumococcal conjugate vaccine in Greater Vancouver, Canada:
      2004-2005.
AB  - Active, population-based surveillance for invasive pneumococcal infections in
      Greater Vancouver (population 473,000 children) demonstrated a rapid, substantial
      decrease in incidence rates for children 6-23 months old with routine infant
      vaccination. In the subpopulation with best case ascertainment disease rates for
      6-23 month olds decreased 84.6% (92.5% for vaccine serotypes).

PMID- 17529876
TI  - Matrix metalloproteinase-9 and tissue inhibitors of metalloproteinases 1 in
      influenza-associated encephalopathy.
AB  - Matrix metalloproteinase-9 (MMP-9) and tissue inhibitors of metalloproteinases 1
      (TIMP-1) play important roles in the function of the blood-brain barrier. Serum
      MMP-9 and TIMP-1 concentrations were determined in influenza virus infection with
      or without neurologic complications. Our results suggest that an imbalance
      between MMP-9 and TIMP-1 damages the blood-brain barrier and promotes febrile
      seizure or encephalopathy in influenza virus infection.

PMID- 17529877
TI  - Prevalence of nasal colonization with methicillin-resistant Staphylococcus aureus
      (MRSA) in children a multicenter cross-sectional study.
AB  - In this cross-sectional multicenter study, we determined the rate of nasal
      carriage of methicillin-resistant Staphylococcus aureus (MRSA) in children
      admitted to 9 training hospitals in Switzerland during 1 month. From 1337
      patients, 1363 nasal swabs were obtained (mean age 6.1 years, median 4.7 years,
      interquartile range 1.3-10.4 years) and 562 (41.3%) grew S. aureus. Only one
      isolate was MRSA (0.18%) which encoded mecA and femA genes as well as SCCmec type
      IV, whereas Panton-Valentine leukocidin (PVL) was absent.

PMID- 17529878
TI  - Palatial erosion caused by Mycobacterium Avium complex in a human
      immunodeficiency virus infected child.
AB  - Oral manifestations of Mycobacterium Avium complex (MAC) are rare and have only
      been described in adults. Here we report a 10-year-old female with advanced human
      immunodeficiency virus infection, who presented with disseminated MAC and an
      erosive left palate defect.

PMID- 17529879
TI  - Salmonella ovarian abscess in an adolescent.
AB  - Salmonella species are a common cause of enteritis and other focal infections,
      including osteomyelitis, septic arthritis, and abscess. We report a case of
      ovarian abscess caused by nontyphoidal Salmonella in an adolescent girl.
      Pediatricians, infectious diseases specialists, and surgical consultants should
      consider this entity within the differential diagnoses of lower quadrant pain and
      adnexal mass in adolescent females.

PMID- 17529880
TI  - Serologic evidence for regional differences in pediatric cryptococcal infection.
AB  - Cryptococcus neoformans is present in areas contaminated with pigeon droppings.
      Unrecognized infections are hypothesized to occur commonly among immunocompetent
      individuals. We used serology to estimate prevalence of cryptococcal infection in
      immunocompetent children from 3 regions. Our results indicate unrecognized
      cryptococcal infections are extremely common in Bronx children, but uncommon in
      children from Dutchess County, NY and the Philippines.

PMID- 17529881
TI  - Insights, challenges, and future directions in irinogenetics.
AB  - Irinotecan is widely used in the treatment of metastatic colorectal cancer and
      extensive small-cell lung cancer. Its use is limited by severe toxicities such as
      neutropenia and delayed-type diarrhea. Irinotecan is converted to its active
      metabolite SN-38. SN-38 is further metabolized to SN-38G by various hepatic and
      extrahepatic UGT1A isozymes, mainly UGT1A1. Impaired glucuronidation activity of
      the UGT1A1 enzyme has been linked with elevated levels of SN-38, leading to
      toxicities. UGT1A1*28 involves an extra TA repeat in the UGT1A1 promoter region
      and is the variant most frequently contributing to interpatient variability in
      irinotecan pharmacokinetics and toxicities. This information led to the revision
      of the irinotecan label by the US Food and Drug Administration. Recently,
      UGT1A1*6 seems to contribute to the risk of toxicity of irinotecan in Asian
      patients. The pharmacogenetics of irinotecan (irinogenetics) is one of few
      promising examples of the application of pharmacogenetics to individualized drug
      therapy. This review summarizes ongoing studies and unanswered questions on
      irinogenetics.

PMID- 17529882
TI  - Prediction of drug clearance in children: impact of allometric exponents, body
      weight, and age.
AB  - In recent years, with the advent of pediatric exclusivity and requirements for
      conducting clinical studies involving children, emphasis has been placed on
      finding safe and efficacious doses of drugs for children. It has been suggested
      that one can predict the clearance (CL) of a drug in children according to this
      equation: CL in the child = Adult CL * (Weight of the child/70)0.75. In light of
      the controversy surrounding the exponent of 0.75 for the prediction of clearance,
      the objectives of the study were as follows: (1) to develop allometric equations
      based on body weight or age to predict clearance of a drug in children; (2) to
      determine if the fixed exponent of 0.75 is a suitable exponent for the prediction
      of clearance in children from adult data, as compared with the allometric
      exponent generated for individual drugs; (3) to determine if the allometric
      equation generated on the basis of age predicts clearance in children better or
      worse than the allometric equation generated on the basis of body weight; and (4)
      to propose a new approach based on the findings of the current evaluation. Five
      methods were used to predict drug clearance in children. Six drugs were used in
      the evaluation, and drug clearance in each child was predicted for a given drug.
      Besides evaluating the exponent of 0.75, allometric equations were developed
      using double log plots of clearance versus body weight or age. The exponents of
      the allometric equations were then used to predict drug clearance by replacement
      of 0.75 in the aforementioned equation. The results of the study indicate that
      0.75 is not the best exponent for prediction of drug clearance in children, and a
      more suitable approach is to develop an allometric relationship for a given drug
      in children. For all 6 drugs, there were 77 children in whom the clearance was
      predicted. There were 48 observations for which error in the predicted clearance
      was 50% or more with use of the exponent 0.75, whereas there were only 13
      observations with prediction error > or = 50% when 0.75 was replaced by an
      allometric exponent developed for a given drug. In order to predict drug
      clearance in children with reasonable accuracy, an allometric equation should be
      developed for every drug and the exponent 0.75 should be replaced by the exponent
      of the allometric equation developed for that drug.

PMID- 17529883
TI  - Protein binding of flucloxacillin in neonates.
AB  - The isoxazolyl penicillins, including flucloxacillin, have the highest levels of
      plasma protein binding among the semisynthetic penicillins. Because only the free
      fraction of the penicillin is pharmacologically active, it would be useful to
      measure both protein-bound and free flucloxacillin to determine its protein
      binding. Until now, flucloxacillin protein binding in newborn infants has been
      investigated in only two studies with relatively small populations. In the
      present study, flucloxacillin protein binding was investigated in 56 (preterm)
      infants aged 3 to 87 days (gestational age, 25-41 weeks). Surplus plasma samples
      from routine gentamicin assays of each infant were collected and combined to
      obtain a sufficiently large sample for analysis. Free flucloxacillin was
      separated from protein-bound flucloxacillin using ultrafiltration. Reversed-phase
      high-performance liquid chromatography with ultraviolet detection was used to
      measure free flucloxacillin concentrations in ultrafiltrate and total
      flucloxacillin concentrations in pooled plasma. Flucloxacillin protein binding
      was 74.5% +/- 13.1% (mean +/- standard deviation) with a high variability among
      the infants (34.3% to 89.7%). High Pearson correlations were found between
      protein binding and the covariates-plasma albumin concentration (r = 0.804, P <
      0.001, n = 18) and plasma creatinine concentration (r = -0.601, P < 0.001, n =
      45). Statistically significant but less striking correlations were found between
      protein binding and gestational age, postconceptional age, body weight, and
      triglyceride concentration. Because of the high variability of protein binding
      among infants, it is difficult to devise a flucloxacillin dosage regimen
      effective for all infants. Individualized dosing, based on free flucloxacillin
      concentrations, might help to optimize treatment of late-onset neonatal sepsis,
      but practical obstacles will probably prevent analysis of free flucloxacillin
      concentrations in newborn infants on a routine basis.

PMID- 17529884
TI  - Renal drug clearance in preterm neonates: relation to prenatal growth.
AB  - Aminoglycosides and glycopeptides are almost exclusively eliminated by renal
      excretion. Postmenstrual age (PMA) is the best predictor of their clearance,
      presumably because it predicts the time course of development of the glomerular
      filtration rate (GFR). Intrauterine growth restriction has an impact on the
      normalized weight of the kidney, on the number of nephrons, on GFR, and on
      tubular function in human perinatal life. We investigated whether prenatal growth
      also affects clearance of drugs such as aminoglycosides or glycopeptides that are
      eliminated through the kidney. Observations collected in two population
      pharmacokinetic studies involving preterm neonates and investigating amikacin and
      vancomycin in the first month of postnatal life were used to estimate the impact
      of prenatal growth (as judged by birth weight for gestational age) on the
      clearance of these drugs. Data from 1212 drug measurements (vancomycin, 648;
      amikacin, 564) in 531 subjects (vancomycin, 249; amikacin, 282) were available
      for study. Neonates born small for gestational age (SGA) were found to have a
      16.2% (coefficient of variation, 12.2%) reduction in drug clearance. This effect
      was present from birth up to the postnatal age of 4 weeks. The covariate size
      (weight 0.75) explained 47.3% of drug clearance; PMA, 25.2%; coadministration of
      a nonselective cyclo-oxygenase inhibitor, 3.5%; renal function, 7.6%; and SGA,
      1.7%. Renal drug clearance is significantly lower in preterm neonates born SGA
      than in appropriate-for-gestational-age (AGA) controls. This reduced clearance
      was observed not only at birth but also up to the postnatal age of 4 weeks.

PMID- 17529885
TI  - CYP2S1 gene polymorphisms in a Korean population.
AB  - Cytochrome P450 2S1 (CYP2S1) is a drug-metabolizing enzyme that shows
      interindividual variations in response to treatments for psoriasis and is
      regarded as a putative prognostic marker for colorectal cancer treatment. To gain
      insight into the genetic basis for the interindividual variations, CYP2S1 gene
      polymorphisms were analyzed in Korean subjects. Using direct sequencing of the
      CYP2S1 gene, 12 genetic variations, which included the two novel nonsynonymous
      mutations CYP2S1 S61N (0.3%) and CYP2S1 L230R (0.8%), were identified in 50
      Korean subjects. Homology modeling predicted the location of the L230R change to
      be near two conserved alpha-helices in the hood of the substrate-binding site.
      Linkage disequilibrium (LD) analysis with seven common CYP2S1 variations showed
      two discrete LD blocks in CYP2S1 gene and consequently a limited number of
      haplotypes. Although the importance of novel CYP2S1 variants and haplotypes
      remains to be discovered, CYP2S1 polymorphisms would provide useful information
      on interindividual variations with respect to CYP2S1 function, which facilitates
      drug response predictions and disease prognosis.

PMID- 17529886
TI  - Influence of UGT1A7 and UGT1A9 intronic I399 genetic polymorphisms on
      mycophenolic acid pharmacokinetics in Japanese renal transplant recipients.
AB  - UGT1A7 and UGT1A9 are uridine diphosphate-glucuronosyltransferase isoforms
      involved in the glucuronidation of mycophenolic acid (MPA). The aim of this study
      was to elucidate MPA pharmacokinetics in UGT1A7 and UGT1A9 intronic I399
      genotypes in Japanese adult renal transplant recipients. Eighty recipients were
      given repeated doses of combination immunosuppressive therapy consisting of
      mycophenolate mofetil and tacrolimus every 12 hours at a designated time (9:00 am
      and 9:00 pm). On day 28 after renal transplantation, plasma MPA concentrations
      were measured by high-performance liquid chromatography. All patients had UGT1A9
      98TT/-275TT/-2152CC and UGT1A10 177GG/605CC genotypes. The UGT1A7*1/*1, *1/*2,
      *1/*3, *2/*3, and *3/*3 genotypes were detected in 35 (43.8%), five (6.2%), 28
      (35.0%), eight (10.0%), and four (5.0%) patients, respectively, and the UGT1A9
      I399C/C, C/T, and T/T genotypes were detected in 12 (15.0%), 33 (41.2%), and 35
      (43.8%) patients of the 80 Japanese recipients. There were no significant
      differences in MPA pharmacokinetics among UGT1A7 or UGT1A9 intronic I399 genotype
      groups. The mean dose-adjusted area under the plasma concentration-time curve
      from zero to 12 hours (AUC0-12) of MPA in UGT1A7*1/*1, *1/*2, *1/*3, *2/*3, and
      *3/*3 were 95, 98, 99, 88, and 86 ng.h/mL/mg, respectively (P = 0.9475). The mean
      dose-adjusted AUC0-12 of MPA in UGT1A9 I399C/C, C/T, and T/T were 87, 99, and 95
      ng.h/mL/mg, respectively (P = 0.6937). The dose-adjusted trough levels of MPA in
      UGT1A9 I399C/C, C/T, and T/T were 5.4, 5.5, and 4.7 ng/mL/mg (P = 0.5845).
      Although UGT1A7*3 and UGT1A9 I399C/C are known to have low-activity variants when
      studied in vitro, they do not have reduced in vivo MPA glucuronidation activity.
      UGT1A7 and UGT1A9 I399 polymorphisms do not contribute to interindividual
      differences in MPA pharmacokinetics.

PMID- 17529887
TI  - Therapeutic drug monitoring and clinical outcomes in epileptic Egyptian patients:
      a gene polymorphism perspective study.
AB  - This work was performed to explore the effect of polymorphism in multidrug
      resistant genes on plasma phenytoin levels and patient outcome to evaluate its
      involvement in drug resistance and toxicity, which is usually associated with
      antiepileptic drugs. Therefore, we genotyped the adenosine triphosphate-binding
      cassette subfamily B member 1 (ABCB1) in 100 patients suffering from partial or
      generalized tonic-clonic seizures and receiving phenytoin and 50 healthy control
      subjects. Steady state plasma phenytoin levels were also determined in the
      epileptic patients. Patients were evaluated after 3 and 6 months and were
      classified either as drug resistant patients or responsive patients. Results
      revealed 37 patients with drug responsive epilepsy and 63 patients with drug
      resistant epilepsy. Genotyping of our patients and control subjects revealed a
      genotype distribution of CC, CT, TT: 55.50%, 38.00%, 6.50% for drug resistant
      patients, CC, CT, TT: 13.50%, 46.00%, 40.50% for drug responsive patients, and
      CC, CT, TT: 24.00%, 48.00%, 28.00% for the control subjects. Patients with drug
      resistant epilepsy were more likely to have the CC than the TT genotype compared
      with either responsive patients (P < 0.0001) or control subjects (P < 0.0001).
      The C polymorphism was over-represented among patients with drug-resistant
      epilepsy as compared with either those with drug-responsive epilepsy (P < 0.001)
      or control subjects (P < 0.001). Of the total 100 epileptic patients, 13 patients
      had their plasma phenytoin levels exceeding the maximum safe concentration. These
      13 patients were more likely to have TT genotype than the CC genotype compared
      with the remainder of patients who had their plasma phenytoin levels at 20
      microg/mL or less. Responsive patients showed no deviation from the control group
      regarding the genotype (P > 0.05) or allele frequency (P > 0.05). In conclusion,
      because most of the antiepileptic drugs are multidrug resistant gene substrates,
      the ABCB1 is thus an important candidate gene for potentially influencing the
      response to antiepileptic drugs. Our findings suggest that using genotype data
      may make it possible to safely reduce the time required to reach an effective
      dose. Therefore, it is a priority to assess the utility of dose adjustment on the
      basis of genotype for these medicines that are substrates for this gene.

PMID- 17529888
TI  - Saliva and serum levetiracetam concentrations in patients with epilepsy.
AB  - Although antiepileptic drug (AED) monitoring in saliva may have some clinical
      applicability, it has not yet come into routine use. The correlation between
      levetiracetam (LEV) saliva and serum concentrations also remains unclear. To
      confirm LEV saliva assay as a useful, noninvasive alternative to serum
      measurement, we investigated the possible correlation between saliva and serum
      LEV concentrations. Samples of saliva and blood were collected from 30 patients
      with epilepsy receiving chronic therapy with LEV as monotherapy or add-on
      therapy, and LEV concentrations were assayed in saliva and serum. Linear
      regression analyses showed a close correlation between saliva and serum LEV
      concentrations (r2 = 0.90; P < 0.001). LEV blood and saliva concentrations were
      linearly related to daily drug doses (r2 = 0.78 and 0.70; P < 0.01). When data
      were analyzed for subgroups (patients receiving LEV in monotherapy, as add-on
      therapy with enzyme-inducer AEDs, and as add-on therapy with noninducer or
      moderate-inducer AEDs), no significant difference was found between saliva and
      serum LEV concentrations among groups. These preliminary results indicate that
      LEV, like other AEDs, can be measured in saliva as an alternative to blood-based
      assays. Saliva LEV collection and assay is a valid noninvasive, more convenient
      alternative to serum measurement.

PMID- 17529889
TI  - A novel enantioselective microassay for the high-performance liquid
      chromatography determination of oxcarbazepine and its active metabolite
      monohydroxycarbazepine in human plasma.
AB  - A simple and innovative assay is described that allows the determination of the
      antiepileptic drug oxcarbazepine and the chiral separation of the two enantiomers
      of its active metabolite monohydroxycarbazepine (licarbazepine). The assay
      requires liquid-liquid extraction of the sample (200 microL) into tert-butyl
      methyl ether and dichloromethane, drying of the organic phase under a nitrogen
      stream, reconstitution with the mobile phase, and injection in the high
      performance liquid chromatography system after filtering. Separation of
      oxcarbazepine, R-(-)-monohydroxycarbazepine, S-(+)-monohydroxycarbazepine, and
      the second-step metabolite 10,11-trans-dihydroxycarbamazepine (racemate) is
      achieved with a Chiralcel ODR column and potassium
      hexafluorophosphate/acetonitrile as mobile phase. Detection is by ultraviolet
      absorbance at 210 nm. Standard curves are linear (r2 > or = 0.999) over the range
      of 0.1 to 25 microg/mL for each analyte with a limit of quantification of 0.1
      microg/mL (1 ng injected) for all compounds. Within-day and between-day precision
      is better than 12% and within-day and between-day accuracy is between 99% and
      116% for each compound. These performance characteristics are adequate for
      pharmacokinetic studies and for therapeutic drug monitoring. However, because the
      two enantiomers of monohydroxycarbazepine exhibit similar pharmacologic activity,
      nonenantioselective assays are likely to be more cost-effective for therapeutic
      drug monitoring purposes.

PMID- 17529890
TI  - Highly specific quantification of ergotamine in urine, blood, and hair samples by
      liquid chromatography-tandem mass spectrometry.
AB  - Ergotamine has been used for therapeutic purposes since the 1950s, usually to
      treat vascular headache. It is highly toxic and in large, repeated doses can
      produce all the symptoms of ergot poisoning. A selective and sensitive method,
      based on liquid chromatography-tandem mass spectrometry (LC-MS2), has been
      developed for quantifying ergotamine in biological fluids with use of a quick and
      easy sample preparation. Ergotamine and the internal standard, trideuterated
      lysergic acid diethylamide, were extracted from human urine, blood, and hair by
      means of liquid-liquid extraction at alkaline pH. Gradient elution on a
      cyanopropyl column was used for chromatographic separation. Positive ion
      electrospray ionization and tandem mass spectrometry determination by collision
      induced dissociation were performed in an ion trap mass spectrometer. The method
      was validated and successfully applied to a case of iatrogenic ergotism resulting
      from the intake of ergotamine tartrate for treating headache. For the first time,
      ergotamine was identified and quantified in hair. The ergotamine concentrations
      measured were 320 pg/mL in blood, 100 pg/mL in urine, 24 pg/mg in proximal hair,
      and 15 pg/mg in distal hair.

PMID- 17529891
TI  - Simultaneous determination of warfarin enantiomers and its metabolite in human
      plasma by column-switching high-performance liquid chromatography with chiral
      separation.
AB  - A simple and sensitive column-switching high-performance liquid chromatographic
      method for the simultaneous determination of warfarin enantiomers and their
      metabolites, 7-hydroxywarfarin enantiomers, in human plasma is described.
      Warfarin enantiomers, 7-hydroxywarfarin enantiomers, and an internal standard,
      diclofenac sodium, were extracted from 1 mL of a plasma sample using diethyl
      ether-chloroform (80:20, v/v). The extract was injected onto column I (TSK
      precolumn BSA-C8, 5 microm, 10 mm x 4.6 mm inside diameter) for cleanup and
      column II (Chiralcel OD-RH analytical column, 150 mm x 4.6 mm inside diameter)
      coupled with a guard column (Chiralcel OD-RH guard column, 10 mm x4.6 mm inside
      diameter) for separation. The mobile phase consisted of phosphate buffer
      acetonitrile (84:16 v/v, pH 2.0) for clean-up and phosphate buffer-acetonitrile
      (45:55 v/v, pH 2.0) for separation. The peaks were monitored with an ultraviolet
      detector set at a wavelength of 312 nm, and total time for chromatographic
      separation was approximately 25 minutes. The validated concentration ranges of
      this method were 3 to 1000 ng/mL for (R)- and (S)-warfarin and 3 to 200 ng/mL for
      (R)- and (S)-7-hydroxywarfarin. Intra- and interday coefficients of variation
      were less than 4.4% and 4.9% for (R)-warfarin and 4.8% and 4.0% for (S)-warfarin,
      and 5.1% and 4.2% for (R)-7-hydroxywarfarin and 5.8% and 5.0% for (S)-7
      hydroxywarfarin at the different concentrations. The limit of quantification was
      3 ng/mL for both warfarin and 7-hydroxywarfarin enantiomers. This method was
      suitable for therapeutic drug monitoring of warfarin enantiomers and was applied
      in a pharmacokinetic study requiring the simultaneous determination of warfarin
      enantiomers and its metabolite, 7-hydroxywarfarin enantiomers, in human
      volunteers.

PMID- 17529892
TI  - Validation of a liquid chromatography-mass spectrometric assay for tacrolimus in
      liver biopsies after hepatic transplantation: correlation with histopathologic
      staging of rejection.
AB  - The aims of this work were both to validate a sensitive and specific method to
      quantify tacrolimus (TAC) in liver biopsies after hepatic transplantation and to
      evaluate the predictive value of either tissue or blood TAC concentrations for
      rejection in 146 adult patients under a TAC-based immunosuppression. Trough blood
      levels were monitored daily during the hospital stay by immunoassay. Liver
      biopsies were routinely performed at day 7 posttransplantation. The tissue assay
      was developed by liquid chromatography-mass spectrometry. The limit of
      quantification was 5 pg/mg, with intra- and interassay precision ranging from
      3.9% to 14.3% and 4.7% to 15.9%, respectively. The extraction efficiency was
      approximately 80%. TAC found in liver biopsies ranged from less than 5 up to 387
      pg/mg. Blood TAC levels ranged from 2.7 to 19.3 ng/mL. Tissue levels displayed
      excellent correlation with liver histopathologic BANFF rejection score, whereas
      blood levels did not. Clinically significant rejections (BANFF scores > or = 6)
      were characterized by mean TAC tissue and blood concentration of 13.1 pg/mg and
      7.6 ng/mL, respectively, whereas these mean values became, respectively, 74.9
      pg/mg (P < 0.05) and 7.1 ng/mL (not significant) for nonclinically significant
      rejection episodes (BANFF < 6). In this study, hepatic tissue TAC concentrations
      were distributed in a wider range and displayed a significantly better
      correlation with the severity of the organ rejection than predose blood levels. A
      tissue TAC concentration less than 30 pg/mg is 89% sensitive and 98% specific to
      discriminate clinically significant cellular rejection. Further studies are
      required to better understand the factors affecting TAC distribution within liver
      tissue (such as carrier proteins and cytochrome genetic polymorphism, liver
      function, age, hepatic blood flow, type of organ transplanted, time
      posttransplantation) and to define its value in the treatment of liver allograft
      rejection.

PMID- 17529893
TI  - Tamoxifen and its main metabolites serum and tissue concentrations in breast
      cancer women.
AB  - Because of a possible relationship between tamoxifen (T) concentrations and
      clinical effects, we initiated a preliminary investigation on serum and tissue
      concentrations of T and its main active metabolites, and 4-hydroxytamoxifen, in
      women with positive breast cancer estrogen receptor. One hundred forty-eight
      patients were studied: 80 were admitted for monitoring of therapeutic serum drug
      concentrations, 22 had tissue concentrations taken at surgery, and 46 patients
      had uterine mucosa levels measured at diagnostic hysteroscopy. Steady-state serum
      concentrations were reached after 1 month of continuous treatment, with
      desmethyltamoxifen being the highest represented derivative from the third week
      onward. There was no relationship between dose (in mg/kg body weight) and steady
      state serum concentrations during therapeutic drug monitoring of patients. The
      highest tissue concentrations were observed in breast lymph-nodes, cancer tissue,
      and uterine mucosa. On the basis of these data, we speculate that T and its
      active metabolites may exert both a defensive role (ie, an obstacle to the
      diffusion of malignant cells through the local lymphatic system) and a harmful
      one (induction of uterine malignancies).

PMID- 17529894
TI  - Pharmacokinetics of mycophenolate mofetil in hematopoietic stem cell transplant
      recipients.
AB  - Mycophenolate mofetil (MMF), a prodrug of mycophenolic acid (MPA), is
      increasingly used in the prophylaxis of graft-versus-host disease (GVHD) after
      hematopoietic stem cell transplantation (HCT). Few pharmacokinetic data are
      available about the use of MMF for this indication. This case series aimed at
      analyzing the pharmacokinetics of MMF in a population of HCT recipients
      representative for everyday practice. From 15 HCT recipients, serial plasma
      samples were taken after twice-daily oral intake of MMF. Plasma concentrations of
      total MPA and its glucuronide metabolites, as well as free MPA, were quantified.
      Median apparent oral MPA clearance (CL/F), apparent half-life, and total MPA area
      under the curve for hours 0 to 12 (AUC0-12, normalized to 1000 mg MMF) were,
      respectively, 56 L/h (range: 29-98 L/h), 2.3 hours (range: 0.8-5.7 hours), and
      18.0 mg*h/L (range: 10-35 mg*h/L). Total MPA concentrations were below 2 mg/L 8
      hours after MMF administration, indicating reduced enterohepatic recirculation.
      Median free MPA AUC0-12 (normalized to 1000 mg MMF) was 224 microg*h/L (range: 56
      411 microg*h/L). Because of high CL/F, total MPA exposure in HCT recipients is
      low and apparent half-life is short in comparison with reference values from
      renal transplantation. Exposure may be improved in HCT recipients by higher or
      more frequent MMF dosing.

PMID- 17529895
TI  - Limited-sampling strategy for the prediction of boosted hard-gel saquinavir
      exposure at a dosage of 1000/100 mg twice daily in human immunodeficiency virus
      infected individuals.
AB  - Area under the concentration time curve (AUC) over a dosing interval is
      considered to be the best estimate of drug exposure in a patient. However,
      determination of this parameter is costly and often impractical, requiring
      multiple samples and a great deal of time and resources. A limited-sampling
      strategy (LSS) may overcome some of these issues, making pharmacokinetic studies
      easier to perform, particularly in a limited-resource setting. The aim of this
      work was to develop and validate a pragmatic LSS for the accurate and precise
      prediction of boosted saquinavir AUC0-12 (AUC over the 12-hour dosing interval)
      at a dosage of 1000/100 mg twice daily. Pharmacokinetic data were obtained from
      34 human immunodeficiency virus (HIV)-infected individuals stable on
      saquinavir/ritonavir-containing therapy, randomly split into two sets (n = 17 per
      set). One set was used to construct prediction models using univariate and
      multivariate analysis (development set), and the second was used to determine the
      predictive performance of the models (validation set). For single samples, 6- and
      10-hour concentrations correlated best with saquinavir AUC0-12 (r2: 0.913 and
      0.911, respectively), yet all single samples failed to produce precise and
      unbiased predictions. However, combinations at 2, 6; 0, 2, 6; 0, 4, 10; 0, 4, 12;
      and 2, 4, 6 hours achieved good predictive performances, and both precise [root
      mean squared relative prediction error (%RMSE): 6.4% to 11.9%] and unbiased [mean
      relative prediction error (%MPE), 95% CI: -2.7%, (-0.8)-2.7 to 1.6%, (-1.8)-4.7]
      estimations of saquinavir AUC0-12. Of these models, concentrations obtained at 0,
      2, 6 and 2, 4, 6 hours are more practical in a clinical setting and are therefore
      the LSS with most potential. Provided that the technique is validated in specific
      patient populations, an LSS approach is a potentially useful tool to evaluate the
      AUC0-12 of saquinavir in resource-limited settings, reducing both costs and
      volumes of blood taken. It may also aid the choice of sampling times for
      population analysis.

PMID- 17529896
TI  - The urinary disposition of intravenously administered 11-nor-9-carboxy-delta-9
      tetrahydrocannabinol in humans.
AB  - The objective of this study was to investigate the fraction of an administered
      dose of 11-nor-9-carboxy-delta-9-tetrahydrocannabinol (THCCOOH) that is actually
      excreted into urine and to determine its urinary half-life independent of the
      parent compound. Ten healthy, male marijuana nonusers who were enrolled in the
      study were administered a single dose of 5 mg THCCOOH by the intravenous route.
      Urine specimens were collected up to 96 hours after administration. Samples were
      extracted before and after alkaline hydrolysis. The concentration of unconjugated
      and total THCCOOH was determined using gas chromatography-mass spectrometry. Most
      of the THCCOOH found in urine was conjugated, with only 0.14 +/- 0.08% of the
      dose present as unconjugated THCCOOH. The amount of conjugated THCCOOH ranged
      from 149.3 to 559.8 (mean +/- SD, 342.8 +/- 117.3) microg, representing a
      recovery of 3% to 11% of the administered dose. The measured amounts of total
      THCCOOH were low and highly varied among individuals. Renal excretion does not
      appear to be the preferred elimination pathway for THCCOOH. Urinary elimination
      half-life of unconjugated and conjugated THCCOOH ranged from 9.0 to 27.4 (mean +/
      SD, 17.3 +/- 5.3) hours and from 10.7 to 27.6 (mean +/- SD, 16.0 +/- 5.0) hours,
      respectively. Although preliminary in nature, the actual urinary elimination half
      life of THCCOOH appears to be significantly shorter than its apparent or terminal
      half-life reported from single or multiple dosing of delta-9-tetrahydrocannabinol
      (THC).

PMID- 17529897
TI  - Bupropion interference with immunoassays for amphetamines and LSD.
AB  - A 50-year-old male patient suddenly had lost consciousness, although he had
      previously been healthy. On arrival at hospital seizures arose. The authors
      investigated a urine sample of the patient, and performed toxicological drug
      screening with immunochemical Cloned Enzyme Donor Immunoassay (CEDIA) assays.
      Positive findings for amphetamines and LSD could not be confirmed. Using gas
      chromatography/mass spectrometry (GC/MS), and liquid chromatography/mass
      spectrometry (LC/MS), the authors identified bupropion, a drug used to aid in
      smoking cessation, as the interfering compound, which may cause false-positive
      results for amphetamines and LSD using the CEDIA assays.

PMID- 17529898
TI  - Amoxicillin pharmacokinetics in (preterm) infants aged 10 to 52 days: effect of
      postnatal age.
AB  - The pharmacokinetic parameters of amoxicillin were determined in 32 newborn
      infants aged 10 to 52 days (mean postnatal age, 24.7 +/- 12.4 days) to improve
      amoxicillin dosing in this age group. Amoxicillin plasma concentrations were
      determined using reversed-phase high-performance liquid chromatography in surplus
      plasma samples from routine gentamicin assays. Amoxicillin pharmacokinetic
      parameters (mean +/- SD) were as follows: first-order elimination constant
      (K(el)) = 0.27 +/- 0.10 h(-1), volume of distribution corrected for body weight
      (V/W) = 0.66 +/- 0.27 L/kg, total body clearance corrected for body weight (CL/W)
      = 0.18 +/- 0.10 Lkg(-1)h(-1), and elimination half-life (t(1/2)) = 3.0 +/- 1.3
      hours. Amoxicillin body clearance was approximately twofold greater in our
      patients compared with published values in younger neonates (mean postnatal age,
      0.76 +/- 1.57 days). Simulation studies using the observed amoxicillin
      pharmacokinetic data suggest an amoxicillin dose of 40 mg/kg administered every 8
      hours in infants older than 9 days postnatal age, independent of gestational age
      and postconceptional age, to achieve satisfactory target plasma amoxicillin
      concentrations less than 140 mg/L and time above minimum inhibitory concentration
      of at least 40%. Prospective evaluation of this suggested new dosage regimen is
      necessary before implementation in the care of ill neonates.

PMID- 17529899
TI  - Enteric-coated mycophenolate sodium provides higher mycophenolic acid predose
      levels compared with mycophenolate mofetil: implications for therapeutic drug
      monitoring.
AB  - The delayed release of mycophenolic acid (MPA) from enteric-coated mycophenolate
      sodium (EC-MPS) may lead to different MPA predose (C0) levels compared with
      mycophenolate mofetil (MMF). A post hoc analysis was performed on MPA morning
      predose values assessed in 88 maintenance renal transplant patients from three
      studies converted from MMF (1000 mg twice a day) to equimolar EC-MPS (720 mg
      twice a day) or vice versa, both in combination with cyclosporine. The median MPA
      predose level was approximately 30% higher when patients received EC-MPS (2.40
      microg/mL; range, 0.49-39.30 microg/mL) compared with MMF (1.83 microg/mL; range,
      <0.1-12.80 microg/mL). Rare cases (3.0%) of high MPA C0 levels 15 microg/mL or
      greater were observed with EC-MPS consistent with a very prolonged release of MPA
      from this formulation. Both EC-MPS and MMF exhibited a poor correlation between
      MPA C0 levels and exposure as assessed by MPA area under the curve. Physicians
      targeting a certain MPA predose level have to be aware of the higher morning C0
      levels with EC-MPS, whereas the overall MPA exposure is not different to MMF.

PMID- 17529900
TI  - Testosterone correlated to symptoms of partial androgen deficiency in aging men
      (PADAM) in an elderly Swedish population.
AB  - OBJECTIVE: To investigate the prevalence of different symptoms of partial
      androgen deficiency in aging men (PADAM) and to correlate them with blood
      concentrations of testosterone and bioavailable testosterone. DESIGN: A total of
      370 men, aged 55 to 75 years, were invited to one of three primary healthcare
      centers in Sweden. They were asked to complete a questionnaire regarding
      demographic data, medical history, mood status, medication, castration therapy
      and smoking, exercise and alcohol habits, as well as different symptoms of PADAM.
      The 10 questions from a previously used questionnaire (the ADAM questionnaire)
      were included. The men were offered blood tests for analyses of testosterone,
      follicle stimulating hormone, luteinizing hormone, steroid hormone-binding
      globulin, and albumin. From these test results, we calculated the bioavailable
      testosterone. RESULTS: Of the questionnaires sent out, 81.6% were returned and
      eligible for evaluation. Blood samples were obtained from 85.8% of men answering
      the questionnaire. Many of the symptoms, including five from the ADAM
      questionnaire, were more common in older age groups (P < 0.05). Three symptoms,
      deterioration in work performance, decreased strength and/or endurance, and
      bothersome hot flushes, were associated with low bioavailable testosterone and/or
      testosterone (P < 0.05). Testosterone and bioavailable testosterone did not
      differ between age groups, but bioavailable testosterone was higher in men with
      three or fewer symptoms on the ADAM questionnaire. CONCLUSIONS: Symptoms
      associated with PADAM often occur in an elderly population, but we could only
      find an association between three symptoms and blood testosterone concentrations,
      one being bothersome hot flushes. It is likely that these symptoms have a more
      complex background than only PADAM.

PMID- 17529901
TI  - Perspective on menopausal vasomotor symptoms, CAM, and the SWAN.

PMID- 17529902
TI  - Changes in liver function and size after a severe thermal injury.
AB  - Hepatic homeostasis and metabolism are essential for survival in critically ill
      and severely burned patients. There is evidence that the liver undergoes
      hypertrophy after burn. However, the extension and the duration of liver
      enlargement are not known. The aim of the present study was to determine the
      changes in liver size, weight, and hepatic protein synthesis in a large
      prospective clinical trial throughout acute hospitalization and up to 12 months
      after burn. Liver size was measured by means of ultrasound, and liver weight was
      calculated weekly during short-term hospital stay and at 6, 9, and 12 months
      after burn. The liver size was then compared with the predicted liver size for
      each individual. The levels of hepatic proteins and enzymes were determined by
      using standard laboratory techniques. One hundred two children were included in
      the study, with 58% +/- 2% total body surface area and 45% +/- 2% third-degree
      burn. Liver size and weight significantly increased during the first week after
      burn (mean +/- SEM, 85% +/- 5%), peaked at 2 weeks after burn (mean +/- SEM, 126%
      +/- 19%), and, at discharge, increased by 89% +/- 10%. At 6, 9, and 12 months,
      the liver weight increased by 40% to 50% compared with the predicted liver
      weight. The hepatic protein synthesis was affected up to 9 months after burn. The
      liver demonstrates a significant enlargement during short-term hospitalization,
      accompanied with impairment in the hepatic protein synthesis. The treatment to
      prevent liver enlargement and the improved impaired function may result in a
      reduction of complications accompanied with liver hypertrophy and failure.

PMID- 17529903
TI  - Role of tumor necrosis factor-alpha in acute pancreatitis: from biological basis
      to clinical evidence.
AB  - Tumor necrosis factor (TNF)-alpha is a pleiotropic cytokine that exerts host
      damaging effects in different autoimmune and inflammatory diseases. It is a key
      regulator of other proinflammatory cytokines and of leukocyte adhesion molecules,
      and it is a priming activator of immune cells. In recent years, several research
      lines-mostly derived from animal models and in vitro studies-suggested that TNF
      alpha plays a pivotal role in the pathogenesis of acute pancreatitis. In
      particular, it contributes to the systemic progression of the inflammatory
      response and to the end-organ dysfunction often observed in severe disease.
      Current clinical applications of TNF-alpha in acute pancreatitis include the
      assessment of blood concentrations to predict disease severity and to identify
      individuals prone to develop complications such as multiple organ failure and
      septic shock. However, TNF-alpha is rapidly cleared from the bloodstream, and
      sensitivity and overall accuracy of its measurement seem strictly time dependent,
      thereby being of potential prognostic value only in the first days after the
      onset of the disease. In parallel, TNF-alpha has been evaluated as a novel
      pharmacologic target for treating pancreatitis. Although promising results have
      been observed in the laboratory, transition to clinical practice seems
      problematic, in particular, in the light of divergent results obtained in sepsis
      trials. Therefore, in future clinical trials pertaining to TNF-alpha
      neutralization in acute pancreatitis, timing of intervention should be related to
      changes in TNF-alpha serum levels, and inclusion and exclusion criteria should be
      accurately selected to better define the population most likely to benefit.

PMID- 17529904
TI  - Red cell transfusion: an essential factor for patient prognosis in surgical
      critical illness?
AB  - In contrast to randomized studies, previous cohort studies identified red cell
      transfusion as an independent predictor of mortality in critically ill patients.
      However, these cohort studies did not adjust for disease severity during
      intensive care unit (ICU) stay. We performed a retrospective, observational
      cohort study using prospectively collected data from March 1, 1993, through
      February 28, 2005. A cohort of 3037 consecutive surgical cases requiring
      intensive care therapy for more than one day was analyzed. We used two different
      sets of potentially confounding covariables (admission variables only or in
      combination with variables reflecting number and extent of organ dysfunction
      during ICU stay). We found that the total number of red cell units which a case
      had received during ICU stay, and the maximum number of units given on a single
      day, were independently associated with an increase in ICU mortality when only
      admission variables were considered for the analysis. After controlling for the
      additional effect of variables reflecting organ dysfunction during ICU stay, we
      found that red cell transfusion was no longer an independent risk factor for
      death. However, there was a significant effect of red cell transfusion on ICU LOS
      in survivors irrespective of the covariable sets used. We conclude that red cell
      transfusion during ICU stay may be only a surrogate marker for disease severity
      and is not causally related to ICU mortality. Relevant side effects of red cell
      transfusion are presumably small and may be only recognizable in surviving cases.

PMID- 17529905
TI  - Functional significance of the TLR4/11367 polymorphism identified in Chinese Han
      population.
AB  - Toll-like receptor 4 (TLR4) is the central signaling receptor for
      lipopolysaccharide (LPS) in mammals. This study was designed to investigate the
      functional significance of the G11367C polymorphism, which is a novel variant we
      identified in the 3' untranslated region of TLR4 gene in Chinese Han population.
      Three hundred seventy healthy volunteers were selected. The TLR4/11367
      polymorphism was genotyped using single-tube bidirectional allele-specific
      amplification method. The TLR4 protein expression on peripheral leukocytes and
      plasma tumor necrosis factor alpha levels were determined by means of flow
      cytometry and enzyme-linked immunosorbent assay. The post-transcriptional effect
      of the 11367 polymorphism was evaluated by means of reporter gene assay and real
      time quantitative polymerase chain reaction. The G11367C polymorphism is a common
      allele in Chinese Han population, with minor allele frequency of 14.7%. In
      response to ex vivo LPS stimulation, the TLR4 expression on the surface of
      peripheral leukocytes and the plasma tumor necrosis factor alpha levels were
      significantly lower in carriers of 11367C variant allele than in carriers of
      11367G allele. This association was allele dose dependent. We also found that the
      activity and the mRNA expression of luciferase was significantly smaller in human
      embryonic kidney 293 cells transfected with construct containing 11367C allele
      than in those transfected with construct containing 11367G allele. Together,
      these results suggest that the TLR4/11367 polymorphism may be a functional single
      nucleotide polymorphism, which could attenuate the LPS-induced transmembrane
      signaling through the alteration of post-transcriptional regulation of 3'
      untranslated region and target gene expression.

PMID- 17529906
TI  - The sex differences of cerebrospinal fluid levels of interleukin 8 and
      antioxidants in asphyxiated newborns.
AB  - Newborn males are more sensitive to brain injury than newborn females are. The
      aim of the present study was to find an explanation for this. We used the neuron
      specific enolase (NSE) levels in the cerebrospinal fluid (CSF) for the
      classification of 32 newborns (19 males and 13 females) on their fifth postnatal
      day. The NSE levels were higher than normal (8.4 +/- 1.6 ng/mL) in 10 newborn
      males and 6 females and were, respectively, considered asphyxiated male and
      female groups. The remaining newborns, 9 males and 7 females, had normal CSF
      levels of NSE and were considered normal newborn male and female groups. The CSF
      samples were measured for 12 cytokines, using a cytokine array kit, and for total
      hydroperoxide and biological antioxidant potentials (BAPs), using the free
      radical analytic system. Among the 12 cytokines measured, only interleukin 8 (IL
      8) was properly detected. The CSF levels of IL-8 were higher in the asphyxiated
      newborn females than in the other three groups. The mean CSF levels of BAPs in
      the asphyxiated newborn females were higher compared with the other three groups,
      but significance was detected only in comparison with the BAP levels in the CSF
      samples of the normal newborn males. There were no differences in total
      hydroperoxide levels among the groups. There are sex-related differences in the
      CSF levels of IL-8 and antioxidants in asphyxiated newborns, with higher levels
      in newborn females; this might contribute in the sexual dimorphism regarding the
      fact that females have better protection from brain injury than the males.

PMID- 17529907
TI  - Effect of brain cooling on brain ischemia and damage markers after fluid
      percussion brain injury in rats.
AB  - Although systemic cooling had recently been reported as effective in improving
      the neurological outcome after traumatic brain injury, several problems are
      associated with whole-body cooling. The present study was conducted to test the
      effectiveness of brain cooling without interference with the core temperature in
      rats after fluid percussion traumatic brain injury (TBI). Brain dialysates
      ischemia (e.g., glutamate and lactate-to-pyruvate ratio) and injury (e.g.,
      glycerol) markers before and after TBI were measured in rats with mild brain
      cooling (33 degrees C) and in the sham control group. Brain cooling was
      accomplished by infusion of 5 mL cold saline via the external jugular vein under
      general anesthesia. The weight loss was determined by the difference between the
      first and third day of body weight after TBI. The maximum grip angle in an
      inclined plane was measured to determine motor performance, whereas the
      percentage of maximal possible effect was used to measure blockade of
      proprioception. The triphenyltetrazolium chloride staining procedures were used
      for cerebral infarction assay. As compared with those of the sham-operated
      controls, the animals with TBI had higher values of extracellular levels of
      glutamate, lactate-to-pyruvate ratio, and glycerol in brain and intracranial
      pressure, but lower values of cerebral perfusion pressure. Brain cooling adopted
      immediately after TBI significantly attenuated the TBI-induced increased cerebral
      ischemia and injury markers, intracranial hypertension, and cerebral
      hypoperfusion. In addition, the TBI-induced cerebral infarction, motor and
      proprioception deficits, and body weight loss evaluated 3 days after TBI were
      significantly attenuated by brain cooling. We successfully demonstrate that brain
      cooling causes attenuation of TBI in rats by reducing cerebral ischemia and
      injury resulting from intracranial hypertension and cerebral hypoperfusion.
      Because jugular venipuncture is an easy procedure frequently used in the
      emergency department, for preservation of brain function, jugular infusion of
      cold saline may be useful in resuscitation for trauma patients.

PMID- 17529908
TI  - Mechanisms of oxidant regulation of monocyte chemotactic protein 1 production in
      human whole blood and isolated mononuclear cells.
AB  - Previous work has demonstrated that reactive oxygen intermediates (ROIs) play an
      important regulatory role in the induction of monocyte chemotactic protein 1 (MCP
      1) in certain cells. This study investigated the mechanisms of ROI regulation of
      MCP-1 gene expression in whole blood and isolated peripheral blood mononuclear
      cells (PBMCs). The antioxidants dimethyl sulfoxide (DMSO), N-acetyl cysteine, and
      dimethyl thiourea significantly inhibited lipopolysaccharide (LPS)-induced MCP-1
      production in either whole blood or isolated blood cells. In contrast,
      interleukin 6 and tumor necrosis factor production were not affected and
      interleukin-1beta levels were actually increased with DMSO treatment. Exogenous
      ROI (either hydrogen peroxide or O2 generated by xanthine/xanthine oxidase)
      stimulated MCP-1 production, which was also inhibited by DMSO. To confirm the
      biological relevance of these findings in vivo, mice treated with DMSO before LPS
      challenge had significantly lower plasma levels of MCP-1. The level of inhibition
      was addressed in experiments which demonstrated that DMSO significantly decreased
      MCP-1 mRNA induced by LPS in whole blood and PBMCs. Cycloheximide treatment did
      not abolish the DMSO inhibition of MCP-1 mRNA, demonstrating that de novo protein
      synthesis is not required. Treatment with actinomycin D showed that DMSO did not
      increase the decay rate of MCP-1 mRNA, indicating that ROI did not change the
      stability of MCP-1 mRNA. These results provide evidence that in whole blood and
      PBMCs, DMSO regulates MCP-1 gene expression by decreasing the induction of MCP-1
      mRNA.

PMID- 17529909
TI  - A model of myocardial inflammation and dysfunction in burn complicated by sepsis.
AB  - Numerous studies have described that an initial injury alters immune function,
      disposing the injured subject to infectious complications. The mechanisms by
      which an initial injury primes the subject, exacerbating the responses to a
      second injury, remain unclear; however, inflammatory cytokines have been
      implicated. The development of "2-hit" models has allowed investigators to
      determine the role of inflammatory mediators in susceptibility to infection after
      injury. A high incidence rate of pneumonia after burn injury and a significant
      increase in postburn mortality led us to develop models of either Gram-positive
      (Streptococcus pneumoniae) or Gram-negative (Klebsiella pneumoniae) sepsis after
      burn injury on 40% of total body surface area in rodents. In this present model,
      we used adult Sprague-Dawley rats to evaluate cardiac function in vitro (using
      Langendorff method) and myocardial inflammation (myocyte secretion of cytokines
      measured using enzyme-linked immunosorbent assay) after burn complicated by
      sepsis. Either burn injury alone or sepsis alone produced myocardial inflammatory
      responses and contractile dysfunction. Either Gram-negative or Gram-positive
      infection exacerbated the myocardial inflammation (increased myocyte secretion of
      tumor necrosis factor alpha, interleukin 1beta, and interleukin 6) above that
      which occurred with burn alone or with infection alone. Burn complicated by
      sepsis exacerbated the myocardial contraction and relaxation defects observed
      with either sepsis alone or burn alone. Inasmuch as sepsis, which occurs after a
      previous injury, increases myocardial inflammation/dysfunction and mortality, the
      development of therapeutic strategies that either decrease inflammatory response
      to the initial injury or provide cardiac support during the postinjury period may
      improve the outcome in injured patients who are at risk for developing sepsis.

PMID- 17529910
TI  - Sepsis-induced myocardial dysfunction.
AB  - Despite the fact that septic patients exhibit altered cardiac function, it is not
      considered a major pathology during sepsis. Thus, the molecular mechanisms
      underlying sepsis-induced myocardial dysfunction have not been studied
      extensively. In a polymicrobial septic rat model, +dP/dt and -dP/dt on day 1 were
      not altered but found depressed later, i.e., at 3 and 7 days postsepsis.
      Diastolic dysfunction characterized by an elevation of the time constant of left
      ventricular relaxation, tau, was evident at 1, 3, and 7 days postsepsis. Recent
      data from our laboratory demonstrated that sepsis-induced cardiodynamic
      alterations correlated with upregulation of TNF receptor-associated death domain,
      Bax, Smac (both mitochondrial and cytosolic fractions), total nuclear factor
      kappaB expression, p38-mitogen-activated protein kinase and c-Jun N-terminal
      kinase phosphorylation, and cytochrome c levels in the rat heart at 3 and 7 days
      postsepsis. Data from various laboratories emphasized that molecular myocardial
      alteration, which occurs during early and late stages of sepsis, needs to be
      elucidated thoroughly. A poor understanding of myocardial signaling during early
      sepsis could be one of the main reasons for limited success of
      pharmacotherapeutic options for sepsis. We anticipate that an increased
      understanding of pathophysiological mechanisms leading to sepsis-induced
      myocardial dysfunction would generate new enthusiasm among various research
      groups in this area of research.

PMID- 17529911
TI  - The extracellular cardiac purine metabolome in sepsis.
AB  - The total cardiac purine metabolome includes all of the adenine and guanine
      nucleoside and nucleosides and related molecules involved throughout the
      intracellular and extracellular compartments and various cell types in the heart.
      In considering purines as molecules involved in autocrine and paracrine
      communication, effective interstitial concentrations of the nucleoside adenosine,
      or purine metabolites, are of greatest interest. These molecules arise from the
      complex interactions between cardiac-specific cell types, including fibroblasts
      and myocytes, and noncardiac cells, such as tissue-resident macrophages and other
      immune cells that have vascular access. In the interstitial environment,
      adenosine can regulate vascular resistance, contractile function, and
      immunochemical interactions. The breakdown of purines can produce reactive oxygen
      species that also influence autocrine and paracrine interactions. A central
      enzyme in this paradigm, adenosine deaminase, is a pivotal molecule in regulating
      the balance between pro-inflammatory and anti-inflammatory signaling cascades. A
      new role for adenosine deaminase as an allosteric regulator of relevant membrane
      proteins has yet to be explored in the heart.

PMID- 17529912
TI  - Oral biopsy. A prospective study on 286 consecutive procedures.
AB  - AIM: The aim of the present study was to survey oral biopsy procedures, with
      particular regard to the incidence of adverse events, patients experience and
      adequacy of the sample. METHODS: This prospective survey was conducted by
      collecting detailed information from consecutive patients undergoing oral biopsy;
      data were obtained on the same day of oral biopsy and after 7 days. RESULTS: Data
      on 286 procedures were collected. About half of the patients had a relevant
      medical history and were taking one or more medications. During biopsy, the
      majority of patients (83%) felt no pain, the others reported mild discomfort.
      Intraoperative adverse events occurred occasionally (4.5%) and were always easily
      resolved; 18% patients admitted taking painkillers in the days following surgery.
      The pathologist was always able to make histological diagnosis, although some
      samples did not include healthy mucosa (32%) or connective tissue (11%).
      CONCLUSION: Oral biopsy is a safe and well accepted surgical procedure.

PMID- 17529913
TI  - Two-dimensional vs three-dimensional assessment of soft tissue facial profile: a
      non invasive study in 6-year-old healthy children.
AB  - AIM: In medical practice, the analysis of facial soft tissues often complement
      (or even supplement) the evaluation of the hard-tissue relationships. Current
      technology provides reference data in three dimensions, but clinical practice
      still uses two-dimensional photographs. In the current study, two-dimensional
      photographic and computerized, three-dimensional angles measured on the facial
      profile of children were compared. METHODS: Two-dimensional angular measurements
      (facial convexity including/excluding the nose; maxillary prominence; nasal
      prominence; nasolabial; mentolabial; maxillo-labio-mandibular; interlabial) were
      obtained on the facial profile photographs of 55 boys and 31 girls aged 6;
      measurements were compared to three-dimensional computerized data collected on 27
      boys and 28 girls of the same age and ethnic group. RESULTS: On average, in boys,
      only the angles of facial convexity including the nose, interlabial, nasolabial
      and maxillo-labio-mandibular showed differences between the means larger than 2
      degrees (up to 2.5 degrees). Statistically significant differences (P<0.05,
      Watson-Williams' test) were found for the angle of facial convexity including the
      nose and the maxillary prominence angle. In girls, differences between the two
      methods larger than 2 degrees were found for the interlabial, maxillo-labio
      mandibular (statistically significant), and mentolabial angles (differences up to
      7 degrees, corresponding to 4% of the relevant mean). CONCLUSION: The two
      dimensional photographic and the three-dimensional computerized data compared in
      the current study, even not superimposable, seemed sufficiently interchangeable,
      at least from a clinical point of view. A particular attention should be given to
      the recording of lip position.

PMID- 17529914
TI  - Electronic dental anaesthesia for third inferior molar surgery.
AB  - AIM: The aim of this study was to evaluate the efficacy of Electronic Dental
      Anaesthesia (EDA) for third molar surgery. METHODS: Third molar extraction under
      regional anaesthesia (inferior alveolar and buccal nerve blocks) was performed in
      2 groups of 30 patients each: group 1 = controls, group 2 = EDA treatment.
      Anxiety and pain level were reported by means of Visual Analogue Scale,
      postoperative pain description with the McGill Pain Questionnaire. A
      postoperative phone interview to all patients was made. Computerized
      randomization was performed; values expressed as mean+/-SD, data comparison
      evaluated by means of ANOVA and chi squared, statistical significance indicated
      by P values <0.05. RESULTS: Features of the patients and surgical interventions
      were similar. EDA has determined lower pain level; moreover, the control patients
      has shown higher values of blood pressure and heart frequency. Phone interview
      has reported no amnesia about the perioperative events. A smaller number of EDA
      treated patients has reported pain during needle prick and/or intraoperatively;
      80% of the EDA treated patients has reported a good opinion about the treatment,
      93% of the patients would repeat the treatment, if needed. CONCLUSION: EDA is a
      complementary analgesic technique for dental surgery. Cardiovascular changes,
      frequently observed during third molar extraction, were not present in the EDA
      treated patients. These data confirm that EDA is able to modify the physiologic
      responses to stressful events, blunting the adrenergic upset, maybe by means of
      an analgesic action on A, fiber and an increase of endorphins' central level.
      These results underline that the complementary use of EDA in the third molar
      extraction may be better than regional anaesthesia alone.

PMID- 17529915
TI  - Eating disorders: a threat for women's health. Oral manifestations in a
      comprehensive overview.
AB  - The incidence of eating disorders has progressively increased over the last
      several years, mainly affecting both the health and quality of life of young
      women. Such disorders are primarily an outlet for manifest psychic suffering and
      secondarily, they jeopardize the integrity and function of multiple organ systems
      resulting in significant morbidity and sometimes, life-threatening outcomes. The
      complex emerging interplay of etiopathogenetic factors poses many challenges in
      their prevention and management, which is further complicated by a reluctance by
      patients with eating disorders to seek medical evaluation and treatment.
      Recognition of the oral manifestations is important because these signs and
      symptoms can provide insights about disease progression and parallel general
      health and psychic status. Oral health care providers may be one of the few
      providers contacted by this patient population seeking recall prophylaxis or
      urgent dental care. Thus, improving understanding and knowledge of both general
      medical aspects of eating disorders and their oral manifestations could be of
      great impact in elevating the attention of health providers towards this group of
      very debilitating disorders and, consequently, improving their overall prognosis.
      In this paper we will review and discuss all these aspects.

PMID- 17529916
TI  - Oral ulcers: three questions on their physiopathology.
AB  - Ulcers and/or erosions can be the final common manifestation, often clinically
      indistinguishable, of a wide and complex spectrum of conditions including
      traumatic lesions, infectious, vesiculo-bullous, neoplastic and gastrointestinal
      diseases. Their formation represents the final outcome of a complex and finely
      orchestrated phenomenon involving both epithelial lining and chorion. Reduction
      of blood flow, cytokine production, cell death, wound repair, all participate to
      the dynamic process which we define as ''ulcer''. However, little is known about
      the mechanisms which crucially contribute in determining the phenomenology of
      ulcer, and some questions still remain unsolved. This paper aims to explain the
      pathophysiology of oral ulcers attempting to answer three questions: the
      mechanism of ulcer development, the site of appearance, and the factors which
      determine the severity and healing time of ulcerative lesions.

PMID- 17529917
TI  - Brain abscess following dental procedures. Case report.
AB  - There have been a number of reports of brain abscess suggesting an odontogenic
      etiology after dental treatment procedures or oral infections, but the diagnosis
      was mainly by exclusion rather than based on evidence. We present a case of a
      brain abscess due to Strepto-coccus constellatus in a 27-year-old-immunocompetent
      woman who underwent extraction of the primary molar and eradication of a
      radicular cyst some weeks before.

PMID- 17529918
TI  - Oxidative stress and critical illness.

PMID- 17529919
TI  - Catheter related bloodstream infection: a continuous challenge in intensive care
      units.

PMID- 17529920
TI  - Effect of morbid obesity on kinetic of desflurane: wash-in wash-out curves and
      recovery times.
AB  - AIM: The aim of this paper was to compare wash-in and wash-out curves of
      desflurane in morbidly obese and nonobese patients. METHODS: Fourteen patients (7
      obese and 7 nonobese) were studied. In the nonobese patients, anaesthesia was
      started by administering 2 mg/kg propofol bolus and a target controlled effect
      site concentration of remifentanil set at 2.5 ng/mL. Obese patients were
      intubated using a flexible fiberoptic bronchoscopic technique facilitated by a
      target controlled effect site concentration of remifentanil set at 2.5 ng/mL.
      After endotracheal intubation, general anaesthesia was started by administering a
      1.5 mg/kg propofol bolus dose. Ten minutes after induction of anaesthesia, 4%
      desflurane was administered for 30 min. Desflurane kinetics was determined by
      collecting end-tidal samples from first breaths at 1, 5, 10, 15, 20, 25 and 30
      min. At last skin suture, the end-tidal concentration of desflurane was recorded
      from 5 consecutive breaths before their discontinuation, then the end-tidal
      samples of the inhalational agent were collected at 0.5, 1, 1.5, 2, 2.5, 3, 3.5,
      4, 4.5 and 5 min after terminating its administration. The period of time from
      discontinuation of desflurane to opening eyes, squeezing the observer's hand,
      extubation, stating the patients' name and providing date of birth was also
      recorded. RESULTS: The FA/FI ratio was higher in the nonobese group from the 10th
      to the 15th min. Wash-out curves of desflurane and recovery times were similar.
      CONCLUSION: Our results show that desflurane provides similar kinetic and
      recovery profiles in obese and nonobese patients.

PMID- 17529921
TI  - A case of lumbar sciatica in a patient with spondylolysis and spondylolysthesis
      and underlying misdiagnosed brucellar discitis.
AB  - We report the case of a patient affected by vertebral pain refractory to
      conventional analgesic therapy with a diagnosis of spondylolysthesis and also the
      affects of a misdiagnosed brucellar spondylodiscitis. The absence of a positive
      response to conventional analgesics, a suggestive medical history (epidemiologic
      data still show a high incidence of Brucella infections for the Province of
      Catania), radiological findings and microbiological tests led to the correct
      diagnosis of algic syndrome in a patient affected by brucellar spondylodiscitis
      with the concomitant presence of retroperitoneal muscular abscess, and a
      previously diagnosed spondylolysthesis. All symptoms improved after correct
      antibrucellar antibiotic therapy and surgical drainage of the retroperitoneal
      abscess. Vertebral pain is a relatively frequent symptom observed in Pain
      Medicine Services; in a zone in which Brucella infections may be considered
      endemic, neurobrucellosis must be considered highly probable in the differential
      diagnosis of several clinical pictures, including vertebral pain that could
      result from vertebral localization of Brucella infection. The role of the Pain
      Medicine Specialist is not only to treat the symptoms, but also to research and
      confirm the etiopathogenetic mechanisms before starting a correct treatment.

PMID- 17529922
TI  - Liver transplantation due to Herpes Simplex virus-related sepsis causing massive
      hepatic necrosis after thoracoscopic thymectomy.
AB  - Following thorascopic thymectomy performed because of myasthenia gravis, a 25
      year-old man was affected by fulminant hepatic failure (FHF) of unknown etiology.
      He was then transferred to our department, where his clinical situation worsened
      with the onset of renal failure, shock, coagulopathy and coma. Given the young
      age of the patient, the immediate availability of a donor, and the absence of a
      definite diagnosis of sepsis at the time, it was decided to proceed with liver
      transplantation. The results of a polymerase chain reaction (PCR) test (a
      technique that was unavailable at the referring hospital), which arrived only a
      few hours later, indicated the presence of herpes simplex virus (HSV) DNA in
      several of the patient's samples; this led to the formulation of a diagnosis of
      FHF due to HSV. It is worth noting that HSV-IgM and HSV-IgG assays had always
      been negative in this patient. Despite acyclovir therapy with initially
      encouraging clinical results, the patient died several days later because the
      viral infection had spread to the graft, lungs, heart, spleen, stomach and
      kidneys. Since evaluating antibody response is not always useful in diagnosing
      HSV infection, and particularly if PCR methodology is unavailable, it is worth
      initiating early empiric antiviral therapy when the etiology of FHF is
      indeterminate This is because the timeliness of treatment while awaiting
      virological confirmation may be critical to survival. If a liver transplantation
      becomes mandatory, careful consideration should be given to the extent of the
      viral infection and its response to therapy because of the possibility of viral
      spread to the graft.

PMID- 17529923
TI  - Bloodless surgery in a patient with thalassemia minor. Usefulness of
      erythropoietin, preoperative blood donation and intraoperative blood salvage.
AB  - A patient with thalassemia minor and idiopathic scoliosis was scheduled for
      posterior vertebral arthrodesis. The diagnosis of thalassemia minor was made
      during the preoperative assessment. Preoperative blood cell count displayed the
      following data: red blood count 5.4 x 106/microL, haemoglobin 11.6 g/dL and
      hematocrit 36.9%. As corrective surgery for scoliosis is associated with major
      blood loss, the patient was scheduled for preoperative treatment with human
      recombinant erythropoietin (rHuEPO), autologous blood donation, intraoperative
      blood cell salvage and administration of tranexamic acid. The use of rHuEPO was
      intended to increase hemoglobin (12.1 g/dL) levels at the moment of surgery
      following the donation of 2 autologous blood units. 1000 mL of salvaged blood
      were processed. The output line of the blood cell salvage machine did not show
      any sign of increased red cell haemolysis. The postoperative course was
      uneventful and the patient was discharged from the postoperative intensive care
      unit on day 7 after surgery with no allogenic blood transfusion. No references
      detailing the use of rHuEPO and autologous blood donation preoperatively in
      patients with thalassemia minor and only one case report discussed the utility of
      intraoperative blood cell salvage in a patient with thalassemia intermedia.
      Although further experience is needed, this case report suggests that even for
      patients with thalassemia minor, methods focused on allogenic blood salvage can
      be used safely.

PMID- 17529924
TI  - The utility of PAX5 immunohistochemistry in the diagnosis of undifferentiated
      malignant neoplasms.
AB  - PAX5 is a B-cell transcription factor whose expression at the protein level is
      reliably detected by immunohistochemistry in routine biopsies. The purpose of
      this study was to investigate whether PAX5 immunohistochemistry has diagnostic
      benefit as a B-cell marker in the work-up of undifferentiated malignant
      neoplasms. Twenty-five cases previously diagnosed as undifferentiated malignant
      neoplasms were selected. In addition, 59 hematolymphoid and 884 non
      hematolymphoid malignancies were studied such that the specificity of PAX5
      immunohistochemistry could be addressed. Two of the 25 (8%) undifferentiated
      neoplasms showed diffuse staining for PAX5, which indicated a B-cell derivation
      for these neoplasms that was not appreciated at the time of initial diagnosis.
      PAX5 staining was detected in the vast majority of hematolymphoid tumors of B
      cell derivation but only in 5 of 884 (less than 1%) non-hematolymphoid tumors.
      Our results further show that PAX5 may be the only detectable marker of B lineage
      in lymphomas that lack or show equivocal CD45RB and CD20 expression. We conclude
      that the addition of PAX5 to a panel of immunohistologic markers used in the
      interrogation of undifferentiated neoplasms is of diagnostic benefit. Its
      expression can also facilitate the diagnosis of classical and nodular lymphocyte
      predominant Hodgkin lymphoma with atypical morphologic and immunohistologic
      features. Lastly, we have shown that the lack of its expression at the protein
      level in many epithelial and mesenchymal neoplasms renders PAX5 expression an
      extremely specific marker of the B lineage.

PMID- 17529925
TI  - Expression of PAX2 in papillary serous carcinoma of the ovary:
      immunohistochemical evidence of fallopian tube or secondary Mullerian system
      origin?
AB  - PAX2 is a urogenital developmental transcription factor expressed in the Wolffian
      ducts, developing kidneys, and Mullerian ducts during embryonic stage. Its
      function in renal development is well documented and its clinical application in
      the diagnosis of lesions of renal origin has been reported recently. However,
      information on its role in the Mullerian-derived genital tract is sparse. In this
      study, we investigated the expression of PAX2 in human female genital tract using
      immunohistochemistry. We demonstrated that PAX2 was expressed specifically in the
      epithelial cells of fallopian tube, endometrial and endocervical glands, but not
      in the stromal tissues in these areas. PAX2 was detected in secondary Mullerian
      structures in the ovary, such as endometriotic and endosalpingiotic glands and
      rete ovarii, but not in ovarian surface epithelium, surface epithelium-derived
      inclusion cysts, stroma, or sex-cord-derived structures such as follicles,
      oocytes, and corpus luteum. In addition, PAX2 was detected in 67% of ovarian
      papillary serous carcinomas (N=36) but rarely in peritoneal malignant
      mesotheliomas, with two exceptions (N=54). Interestingly, the two PAX2-positive
      'peritoneal malignant mesotheliomas' were from female patients and were positive
      for estrogen receptor. The significance of expression of PAX2 and estrogen
      receptor in these cases is under investigation. Taken together, we suggest that
      PAX2 is a novel Mullerian-specific epithelial marker when used in proper clinical
      settings. Identification of PAX2 in the majority of papillary serous carcinomas
      of the ovary but not in the ovarian surface epithelium or epithelium-derived
      inclusion cysts suggests that this malignant epithelial tumor may be directly
      derived from the primary or secondary Mullerian epithelium in or surrounding the
      ovary, rather than from the surface epithelium or its derivatives.

PMID- 17529926
TI  - Chromosomal analysis of Barrett's cells: demonstration of instability and
      detection of the metaplastic lineage involved.
AB  - Barrett's esophagus is lined by columnar and goblets cells with gastric and
      intestinal characteristics. Despite the association between goblet elements and
      malignancy, it was not demonstrated that other columnar cells lineages are not
      related to neoplasia. Chromosomal abnormalities were described in metaplasia
      adjacent to Barrett's neoplasia, but it is unknown which metaplastic lineages are
      involved. This work assessed the frequency and the type of chromosomal
      abnormalities in Barrett's esophagus without neoplasia and performed the
      identification of the metaplastic cells carrying chromosomal gains. Barrett's
      esophagus biopsies were collected and processed for short-term cell culture and
      cytogenetic analysis. Combined immunofluorescence/fluorescence in situ
      hybridization was performed in cases exhibiting chromosomal gains by using
      antisera against intestinal (MUC2) and gastric (MUC5AC and MUC6) apomucins and
      chromosome pericentromeric alpha satellite DNA probes for the chromosomes
      involved. Each case was scored for the number of spots (0, 1, 2, >2) in 200
      nonoverlapping nuclei. Columnar and goblet cells were separately assessed. Short
      term cell cultures were achieved in 40/60 cases (67%). There were clonal
      abnormalities in 27/40 cases (68%) and tetraploid (4n) clones in 10/40 (25%).
      Structural alterations were detected in 14/40 (35%) with recurrent breakpoints at
      1q21, 15q15 and 15q22. Numerical changes (trisomies 7 and 18 and loss of Y)
      occurred in 16/40 (40%). Gains of chromosomes 7 and 18 were more frequent in
      columnar than in goblet cells (9.8% vs 0.7% (P<0.05)) and (7.9 vs 1.9% (P<0.05))
      respectively. These alterations were detected in cells exhibiting gastric as well
      as intestinal features and were more frequent in cells without apomucin
      production. CONCLUSIONS: (1) chromosomal instability is a common finding in
      Barrett's esophagus without neoplasia. (2) The two metaplastic populations are
      committed, chromosomal gains being more frequent in columnar nongoblet than in
      goblet cells. (3) The two metaplastic phenotypes, gastric and intestinal, are
      equally involved.

PMID- 17529968
TI  - Efficiency enhancement in low-bandgap polymer solar cells by processing with
      alkane dithiols.
AB  - High charge-separation efficiency combined with the reduced fabrication costs
      associated with solution processing and the potential for implementation on
      flexible substrates make 'plastic' solar cells a compelling option for tomorrow's
      photovoltaics. Attempts to control the donor/acceptor morphology in bulk
      heterojunction materials as required for achieving high power-conversion
      efficiency have, however, met with limited success. By incorporating a few volume
      per cent of alkanedithiols in the solution used to spin-cast films comprising a
      low-bandgap polymer and a fullerene derivative, the power-conversion efficiency
      of photovoltaic cells (air-mass 1.5 global conditions) is increased from 2.8% to
      5.5% through altering the bulk heterojunction morphology. This discovery can
      potentially enable morphological control in bulk heterojunction materials where
      thermal annealing is either undesirable or ineffective.

PMID- 17529967
TI  - Genome-wide association study identifies novel breast cancer susceptibility loci.
AB  - Breast cancer exhibits familial aggregation, consistent with variation in genetic
      susceptibility to the disease. Known susceptibility genes account for less than
      25% of the familial risk of breast cancer, and the residual genetic variance is
      likely to be due to variants conferring more moderate risks. To identify further
      susceptibility alleles, we conducted a two-stage genome-wide association study in
      4,398 breast cancer cases and 4,316 controls, followed by a third stage in which
      30 single nucleotide polymorphisms (SNPs) were tested for confirmation in 21,860
      cases and 22,578 controls from 22 studies. We used 227,876 SNPs that were
      estimated to correlate with 77% of known common SNPs in Europeans at r2 > 0.5.
      SNPs in five novel independent loci exhibited strong and consistent evidence of
      association with breast cancer (P < 10(-7)). Four of these contain plausible
      causative genes (FGFR2, TNRC9, MAP3K1 and LSP1). At the second stage, 1,792 SNPs
      were significant at the P < 0.05 level compared with an estimated 1,343 that
      would be expected by chance, indicating that many additional common
      susceptibility alleles may be identifiable by this approach.

PMID- 17529969
TI  - Zeolite A imidazolate frameworks.
AB  - Faujasite (FAU) and zeolite A (LTA) are technologically important porous zeolites
      (aluminosilicates) because of their extensive use in petroleum cracking and water
      softening. Introducing organic units and transition metals into the backbone of
      these types of zeolite allows us to expand their pore structures, enhance their
      functionality and access new applications. The invention of metal-organic
      frameworks and zeolitic imidazolate frameworks (ZIFs) has provided materials
      based on simple zeolite structures where only one type of cage is present.
      However, so far, no metal-organic analogues based on FAU or LTA topologies exist
      owing to the difficulty imposed by the presence of two types of large cage (super
      and beta-cages for FAU, alpha- and beta-cages for LTA). Here, we have identified
      a strategy to produce an LTA imidazolate framework in which both the link
      geometry and link-link interactions play a decisive structure-directing role. We
      describe the synthesis and crystal structures of three porous ZIFs that are
      expanded analogues of zeolite A; their cage walls are functionalized, and their
      metal ions can be changed without changing the underlying LTA topology. Hydrogen,
      methane, carbon dioxide and argon gas adsorption isotherms are reported and the
      selectivity of this material for carbon dioxide over methane is demonstrated.

PMID- 17529970
TI  - Dynamic in situ observation of rapid size and shape change of supported Pd
      nanoparticles during CO/NO cycling.
AB  - Understanding and improving the behaviour of supported precious-metal catalysts
      for a vast array of environmentally and economically important processes is a
      central area of research in catalysis. The removal of toxic gases such as CO and
      NO, without forming others (such as N(2)O), is particularly important. By
      combining energy-dispersive extended X-ray absorption fine-structure spectroscopy
      with a vibrational spectroscopy (infrared) and mass spectrometry, at high time
      resolution, in a single in situ experiment, we dynamically observe and quantify
      CO-, and subsequent NO-, induced size and shape changes of Pd nanoparticles
      during CO/NO cycling. In doing so we demonstrate a novel, non-oxidative
      redispersion (for example, an increase in metal surface area) mechanism, and
      suggest a model to bridge the structural and reactive functions of supported Pd
      catalysts.

PMID- 17529971
TI  - A ROCK inhibitor permits survival of dissociated human embryonic stem cells.
AB  - Poor survival of human embryonic stem (hES) cells after cell dissociation is an
      obstacle to research, hindering manipulations such as subcloning. Here we show
      that application of a selective Rho-associated kinase (ROCK) inhibitor, Y-27632,
      to hES cells markedly diminishes dissociation-induced apoptosis, increases
      cloning efficiency (from approximately 1% to approximately 27%) and facilitates
      subcloning after gene transfer. Furthermore, dissociated hES cells treated with Y
      27632 are protected from apoptosis even in serum-free suspension (SFEB) culture
      and form floating aggregates. We demonstrate that the protective ability of Y
      27632 enables SFEB-cultured hES cells to survive and differentiate into Bf1(+)
      cortical and basal telencephalic progenitors, as do SFEB-cultured mouse ES cells.

PMID- 17529972
TI  - Improved antimicrobial peptides based on acyl-lysine oligomers.
AB  - We describe peptidomimetic oligomers that show rapid, nonhemolytic, broad
      spectrum bactericidal properties in mice and do not induce the emergence of
      resistance. The oligomers contain acyl chains, which prevent the formation of
      stable secondary structure. This design appears advantageous over conventional
      antimicrobial peptides with respect to in vivo efficacy and safety, and may
      provide a convenient platform for the development of peptide antibiotics.

PMID- 17529973
TI  - A genome-wide association study identifies alleles in FGFR2 associated with risk
      of sporadic postmenopausal breast cancer.
AB  - We conducted a genome-wide association study (GWAS) of breast cancer by
      genotyping 528,173 SNPs in 1,145 postmenopausal women of European ancestry with
      invasive breast cancer and 1,142 controls. We identified four SNPs in intron 2 of
      FGFR2 (which encodes a receptor tyrosine kinase and is amplified or overexpressed
      in some breast cancers) that were highly associated with breast cancer and
      confirmed this association in 1,776 affected individuals and 2,072 controls from
      three additional studies. Across the four studies, the association with all four
      SNPs was highly statistically significant (P(trend) for the most strongly
      associated SNP (rs1219648) = 1.1 x 10(-10); population attributable risk = 16%).
      Four SNPs at other loci most strongly associated with breast cancer in the
      initial GWAS were not associated in the replication studies. Our summary results
      from the GWAS are available online in a form that should speed the identification
      of additional risk loci.

PMID- 17529974
TI  - Common variants on chromosomes 2q35 and 16q12 confer susceptibility to estrogen
      receptor-positive breast cancer.
AB  - Familial clustering studies indicate that breast cancer risk has a substantial
      genetic component. To identify new breast cancer risk variants, we genotyped
      approximately 300,000 SNPs in 1,600 Icelandic individuals with breast cancer and
      11,563 controls using the Illumina Hap300 platform. We then tested selected SNPs
      in five replication sample sets. Overall, we studied 4,554 affected individuals
      and 17,577 controls. Two SNPs consistently associated with breast cancer:
      approximately 25% of individuals of European descent are homozygous for allele A
      of rs13387042 on chromosome 2q35 and have an estimated 1.44-fold greater risk
      than noncarriers, and for allele T of rs3803662 on 16q12, about 7% are homozygous
      and have a 1.64-fold greater risk. Risk from both alleles was confined to
      estrogen receptor-positive tumors. At present, no genes have been identified in
      the linkage disequilibrium block containing rs13387042. rs3803662 is near the 5'
      end of TNRC9 , a high mobility group chromatin-associated protein whose
      expression is implicated in breast cancer metastasis to bone.

PMID- 17529975
TI  - A conserved molecular pathway mediates myoblast fusion in insects and
      vertebrates.
AB  - Skeletal muscles arise by fusion of precursor cells, myoblasts, into
      multinucleated fibers. In vertebrates, mechanisms controlling this essential step
      in myogenesis remain poorly understood. Here we provide evidence that Kirrel, a
      homolog of receptor proteins that organize myoblast fusion in Drosophila
      melanogaster, is necessary for muscle precursor fusion in zebrafish. Within
      developing somites, Kirrel expression localized to membranes of fusion-competent
      myoblasts of the fast-twitch lineage. Unlike wild-type myoblasts that form
      spatially arrayed syncytial (multinucleated) fast myofibers, those deficient in
      Kirrel showed a significant reduction in fusion capacity. Inhibition of Rac, a
      GTPase and the most downstream intracellular transducer of the fusion signal in
      D. melanogaster, also compromised fast-muscle precursor fusion in zebrafish.
      However, unlike in D. melanogaster, constitutive Rac activation in zebrafish led
      to hyperfused giant syncytia, highlighting an entirely new function for this
      protein in zebrafish for gating the number and polarity of fusion events. These
      findings uncover a substantial degree of evolutionary conservation in the genetic
      regulation of myoblast fusion.

PMID- 17529976
TI  - Spontaneous DNA breakage in single living Escherichia coli cells.
AB  - Spontaneous DNA breakage is predicted to be a frequent, inevitable consequence of
      DNA replication and is thought to underlie much of the genomic change that fuels
      cancer and evolution. Despite its importance, there has been little direct
      measurement of the amounts, types, sources and fates of spontaneous DNA lesions
      in living cells. We present a direct, sensitive flow cytometric assay in single
      living Escherichia coli cells for DNA lesions capable of inducing the SOS DNA
      damage response, and we report its use in quantification of spontaneous DNA
      double-strand breaks (DSBs). We report efficient detection of single chromosomal
      DSBs and rates of spontaneous breakage approximately 20- to 100-fold lower than
      predicted. In addition, we implicate DNA replication in the origin of spontaneous
      DSBs with the finding of fewer spontaneous DSBs in a mutant with altered DNA
      polymerase III. The data imply that spontaneous DSBs induce genomic changes and
      instability 20-100 times more potently than previously appreciated. Finally, FACS
      demonstrated two main cell fates after spontaneous DNA damage: viability with or
      without resumption of proliferation.

PMID- 17529977
TI  - Tissue-specific transcriptional regulation has diverged significantly between
      human and mouse.
AB  - We demonstrate that the binding sites for highly conserved transcription factors
      vary extensively between human and mouse. We mapped the binding of four tissue
      specific transcription factors (FOXA2, HNF1A, HNF4A and HNF6) to 4,000
      orthologous gene pairs in hepatocytes purified from human and mouse livers.
      Despite the conserved function of these factors, from 41% to 89% of their binding
      events seem to be species specific. When the same protein binds the promoters of
      orthologous genes, approximately two-thirds of the binding sites do not align.

PMID- 17529978
TI  - FCGR3B copy number variation is associated with susceptibility to systemic, but
      not organ-specific, autoimmunity.
AB  - Naturally occurring variation in gene copy number is increasingly recognized as a
      heritable source of susceptibility to genetically complex diseases. Here we
      report strong association between FCGR3B copy number and risk of systemic lupus
      erythematosus (P = 2.7 x 10(-8)), microscopic polyangiitis (P = 2.9 x 10(-4)) and
      Wegener's granulomatosis in two independent cohorts from the UK (P = 3 x 10(-3))
      and France (P = 1.1 x 10(-4)). We did not observe this association in the organ
      specific Graves' disease or Addison's disease. Our findings suggest that low
      FCGR3B copy number, and in particular complete FCGR3B deficiency, has a key role
      in the development of systemic autoimmunity.

PMID- 17529979
TI  - Pervasive combinatorial modification of histone H3 in human cells.
AB  - We developed a platform using hydrophilic interaction chromatography and high
      resolution tandem mass spectrometry (MS) for analyses of histone H3 that allows
      comprehensive characterization of 'histone codes' at the molecular level. We
      identified over 150 differentially modified forms of histone H3.2 in
      asynchronously grown and butyrate-treated HeLa cells, revealing pervasive
      combinatorial modification previously unaccounted for by other techniques and
      providing a clarified estimate of the molecular diversity of histone H3 in
      mammals.

PMID- 17529980
TI  - Strategy for the fine characterization of glycosyltransferase specificity using
      isotopomer assembly.
AB  - Glycosylation, which represents the most complex posttranslational modification
      (PTM) event during protein maturation, has a vital role in biological processes.
      Glycan biosynthesis is orchestrated by numerous glycosyltransferases, each
      displaying different selectivities for multiple reaction sites. The precise
      specificities of these enzymes have been difficult to study because of the lack
      of available substrates of defined structure and problems associated with the
      analyses. Moreover, the analysis of glycans is extremely difficult owing to the
      structural complexity of the glycan chain. Here we describe a new strategy for
      the fine characterization of enzyme specificity using substrate isotopomer
      assemblies. Because isotopomer assemblies contain a sugar residue that is
      position-specifically labeled with a stable isotope, we can use tandem mass
      spectrometry (MS/MS) to assign the structure of positional isomers generated by
      glycosylation. We demonstrated the analysis of substrate specificities of five
      beta4-galactosyltransferases (beta4GalT-I, -II, -III, -IV and -V) using our
      strategy.

PMID- 17529981
TI  - Retinaldehyde represses adipogenesis and diet-induced obesity.
AB  - The metabolism of vitamin A and the diverse effects of its metabolites are
      tightly controlled by distinct retinoid-generating enzymes, retinoid-binding
      proteins and retinoid-activated nuclear receptors. Retinoic acid regulates
      differentiation and metabolism by activating the retinoic acid receptor and
      retinoid X receptor (RXR), indirectly influencing RXR heterodimeric partners.
      Retinoic acid is formed solely from retinaldehyde (Rald), which in turn is
      derived from vitamin A. Rald currently has no defined biologic role outside the
      eye. Here we show that Rald is present in rodent fat, binds retinol-binding
      proteins (CRBP1, RBP4), inhibits adipogenesis and suppresses peroxisome
      proliferator-activated receptor-gamma and RXR responses. In vivo, mice lacking
      the Rald-catabolizing enzyme retinaldehyde dehydrogenase 1 (Raldh1) resisted diet
      induced obesity and insulin resistance and showed increased energy dissipation.
      In ob/ob mice, administrating Rald or a Raldh inhibitor reduced fat and increased
      insulin sensitivity. These results identify Rald as a distinct transcriptional
      regulator of the metabolic responses to a high-fat diet.

PMID- 17529982
TI  - Lymphoid reservoirs of antigen-specific memory T helper cells.
AB  - How vaccines control the development of antigen-specific effector and memory T
      helper cells is central to protective immunity but remains poorly understood.
      Here we found that protein vaccination selected high-affinity, CXCR5+ICOS(hi)
      follicular B-helper T cells (T(FH) cells) that developed in draining lymphoid
      tissue to regulate B cell responses. In the memory phase, reservoirs of antigen
      specific CXCR5+ICOS(lo) T(FH) cells persisted with less effector activity but
      accelerated antigen-recall ability. This new compartment of memory T(FH) cells
      was retained in draining lymphoid sites with antigen-specific memory B cells,
      persistent complexes of peptide and major histocompatibility complex class II and
      continued expression of CD69. Thus, protein vaccination promotes B cell immunity
      by selecting high-affinity effector T(FH) cells and creating lymphoid reservoirs
      of antigen-specific memory T(FH) cells in vivo.

PMID- 17529983
TI  - L-selectin-negative CCR7- effector and memory CD8+ T cells enter reactive lymph
      nodes and kill dendritic cells.
AB  - T lymphocytes lacking the lymph node-homing receptors L-selectin and CCR7 do not
      migrate to lymph nodes in the steady state. Instead, we found here that lymph
      nodes draining sites of mature dendritic cells or adjuvant inoculation recruited
      L-selectin-negative CCR7- effector and memory CD8+ T cells. This recruitment
      required CXCR3 expression on T cells and occurred through high endothelial
      venules in concert with lumenal expression of the CXCR3 ligand CXCL9. In reactive
      lymph nodes, recruited T cells established stable interactions with and killed
      antigen-bearing dendritic cells, limiting the ability of these dendritic cells to
      activate naive CD4+ and CD8+ T cells. The inducible recruitment of blood-borne
      effector and memory T cells to lymph nodes may represent a mechanism for
      terminating primary and limiting secondary immune responses.

PMID- 17529984
TI  - Cyclin-dependent kinase 5 governs learning and synaptic plasticity via control of
      NMDAR degradation.
AB  - Learning is accompanied by modulation of postsynaptic signal transduction
      pathways in neurons. Although the neuronal protein kinase cyclin-dependent kinase
      5 (Cdk5) has been implicated in cognitive disorders, its role in learning has
      been obscured by the perinatal lethality of constitutive knockout mice. Here we
      report that conditional knockout of Cdk5 in the adult mouse brain improved
      performance in spatial learning tasks and enhanced hippocampal long-term
      potentiation and NMDA receptor (NMDAR)-mediated excitatory postsynaptic currents.
      Enhanced synaptic plasticity in Cdk5 knockout mice was attributed to reduced NR2B
      degradation, which caused elevations in total, surface and synaptic NR2B subunit
      levels and current through NR2B-containing NMDARs. Cdk5 facilitated the
      degradation of NR2B by directly interacting with both it and its protease,
      calpain. These findings reveal a previously unknown mechanism by which Cdk5
      facilitates calpain-mediated proteolysis of NR2B and may control synaptic
      plasticity and learning.

PMID- 17529986
TI  - The mirror neuron system is more active during complementary compared with
      imitative action.
AB  - We assessed the role of the human mirror neuron system (MNS) in complementary
      actions using functional magnetic resonance imaging while participants prepared
      to execute imitative or complementary actions. The BOLD signal in the right
      inferior frontal gyrus and bilateral inferior parietal lobes was greater during
      preparation of complementary than during imitative actions, suggesting that the
      MNS may be essential in dynamically coupling action observation to action
      execution.

PMID- 17529985
TI  - Cortical reorganization consistent with spike timing-but not correlation
      dependent plasticity.
AB  - The receptive fields of neurons in primary visual cortex that are inactivated by
      retinal damage are known to 'shift' to nondamaged retinal locations, seemingly
      due to the plasticity of intracortical connections. We have observed in cats that
      these shifts occur in a pattern that is highly convergent, even among receptive
      fields that are separated by large distances before inactivation. Here we show,
      using a computational model of primary visual cortex, that the observed
      convergent shifts are inconsistent with the common assumption that the underlying
      intracortical connection plasticity is dependent on the temporal correlation of
      pre- and postsynaptic action potentials. The shifts are, however, consistent with
      the hypothesis that this plasticity is dependent on the temporal order of pre-
      and postsynaptic action potentials. This convergent reorganization seems to
      require increased neuronal gain, revealing a mechanism that networks may use to
      selectively facilitate the didactic transfer of neuronal response properties.

PMID- 17529987
TI  - Cytoplasmic and mitochondrial protein translation in axonal and dendritic
      terminal arborization.
AB  - We identified a mutation in Aats-gly (also known as gars or glycyl-tRNA
      synthetase), the Drosophila melanogaster ortholog of the human GARS gene that is
      associated with Charcot-Marie-Tooth neuropathy type 2D (CMT2D), from a mosaic
      genetic screen. Loss of gars in Drosophila neurons preferentially affects the
      elaboration and stability of terminal arborization of axons and dendrites. The
      human and Drosophila genes each encode both a cytoplasmic and a mitochondrial
      isoform. Using additional mutants that selectively disrupt cytoplasmic or
      mitochondrial protein translation, we found that cytoplasmic protein translation
      is required for terminal arborization of both dendrites and axons during
      development. In contrast, disruption of mitochondrial protein translation
      preferentially affects the maintenance of dendritic arborization in adults. We
      also provide evidence that human GARS shows equivalent functions in Drosophila,
      and that CMT2D causal mutations show loss-of-function properties. Our study
      highlights different demands of protein translation for the development and
      maintenance of axons and dendrites.

PMID- 17529989
TI  - Reduction in O-18 dose--at what cost?

PMID- 17529991
TI  - Structural basis of histone demethylation by LSD1 revealed by suicide
      inactivation.
AB  - Histone methylation regulates diverse chromatin-templated processes, including
      transcription. The recent discovery of the first histone lysine-specific
      demethylase (LSD1) has changed the long-held view that histone methylation is a
      permanent epigenetic mark. LSD1 is a flavin adenine dinucleotide (FAD)-dependent
      amine oxidase that demethylates histone H3 Lys4 (H3-K4). However, the mechanism
      by which LSD1 achieves its substrate specificity is unclear. We report the
      crystal structure of human LSD1 with a propargylamine-derivatized H3 peptide
      covalently tethered to FAD. H3 adopts three consecutive gamma-turns, enabling an
      ideal side chain spacing that places its N terminus into an anionic pocket and
      positions methyl-Lys4 near FAD for catalysis. The LSD1 active site cannot
      productively accommodate more than three residues on the N-terminal side of the
      methyllysine, explaining its H3-K4 specificity. The unusual backbone conformation
      of LSD1-bound H3 suggests a strategy for designing potent LSD1 inhibitors with
      therapeutic potential.

PMID- 17529992
TI  - Structural and biochemical insights into the regulation of protein phosphatase 2A
      by small t antigen of SV40.
AB  - The small t antigen (ST) of DNA tumor virus SV40 facilitates cellular
      transformation by disrupting the functions of protein phosphatase 2A (PP2A)
      through a poorly defined mechanism. The crystal structure of the core domain of
      SV40 ST bound to the scaffolding subunit of human PP2A reveals that the ST core
      domain has a novel zinc-binding fold and interacts with the conserved ridge of
      HEAT repeats 3-6, which overlaps with the binding site for the B' (also called
      PR61 or B56) regulatory subunit. ST has a lower binding affinity than B' for the
      PP2A core enzyme. Consequently, ST does not efficiently displace B' from PP2A
      holoenzymes in vitro. Notably, ST inhibits PP2A phosphatase activity through its
      N-terminal J domain. These findings suggest that ST may function mainly by
      inhibiting the phosphatase activity of the PP2A core enzyme, and to a lesser
      extent by modulating assembly of the PP2A holoenzymes.

PMID- 17529993
TI  - SET and PARP1 remove DEK from chromatin to permit access by the transcription
      machinery.
AB  - The histone chaperone SET is required for transcription of chromatin templates by
      RNA polymerase Pol II (Pol II) in vitro. Here we uncover a positive role for SET
      in dislodging DEK and PARP1, which restrict access to chromatin in the absence of
      SET and the PARP1 substrate NAD(+). SET binds chromatin, dissociating DEK and
      PARP1 to allow transcription in the absence of NAD(+). In the absence of SET,
      depletion of DEK restores chromatin accessibility to endonuclease but does not
      permit Mediator recruitment or transcription. In the presence of NAD(+), PARP1
      poly(ADP-ribosyl)ates and evicts DEK (and itself) from chromatin to permit
      Mediator loading and transcription independent of SET. An artificial DEK variant
      resistant to SET and PARP1 represses transcription, indicating a requirement for
      DEK removal. Therefore, SET, DEK and PARP1 constitute a network governing access
      to chromatin by the transcription machinery.

PMID- 17529994
TI  - The DIX domain of Dishevelled confers Wnt signaling by dynamic polymerization.
AB  - The Wnt signaling pathway controls numerous cell fates in animal development and
      is also a major cancer pathway. Dishevelled (Dvl) transduces the Wnt signal by
      interacting with the cytoplasmic Axin complex. Dvl and Axin each contain a DIX
      domain whose molecular properties and structure are unknown. Here, we demonstrate
      that the DIX domain of Dvl2 mediates dynamic polymerization, which is essential
      for the signaling activity of Dvl2. The purified domain polymerizes gradually,
      reversibly and in a concentration dependent manner, ultimately forming fibrils.
      The Axin DIX domain has a novel structural fold largely composed of beta-strands
      that engage in head-to-tail self-interaction to form filaments in the crystal.
      The DIX domain thus seems to mediate the formation of a dynamic interaction
      platform with a high local concentration of binding sites for transient Wnt
      signaling partners; this represents a previously uncharacterized mechanistic
      principle, signaling by reversible polymerization.

PMID- 17529995
TI  - Highly diverged MHC class I mismatches are acceptable for haematopoietic stem
      cell transplantation.
AB  - A fully major histocompatilbility complex (MHC) matched donor is not available
      for the majority of patients in need of a haematopoietic stem cell
      transplantation (SCT), which illustrates the need for a tool to define acceptable
      MHC disparities. Previously, we noticed that a variety of single MHC class I
      mismatched allogeneic donor-recipient pairs did not elicit an allogeneic
      cytotoxic-lymphocyte (CTL) response in vitro if the MHC amino-acid sequences had
      five or more differences in the alpha-helices plus five or more differences in
      the beta-sheet (> or =5alpha5beta) (7). To address the clinical relevance of this
      observation, we analysed CTL precursor (CTLp) assay outcome and SCT outcome in 53
      Dutch recipients of a single MHC class I mismatched graft from an unrelated
      donor. Overall patient survival was 44% after 4 years. In multivariate analysis,
      recipients of a > or =5alpha5beta mismatched graft with negative CTLp frequencies
      in vitro before transplantation demonstrated superior survival: survival at 4
      years was 80% as compared to 47% in recipients of other mismatched grafts with
      negative CTLp frequencies (hazard ratio=0.131; 95% CI=(0.03-0.61); P=0.009). This
      option of acceptable mismatches may enlarge the pool of potentially acceptable
      stem cell donors.

PMID- 17529996
TI  - Efficacy of caspofungin as secondary prophylaxis in patients undergoing
      allogeneic stem cell transplantation with prior pulmonary and/or systemic fungal
      infection.
AB  - Transplanted patients with a history of invasive fungal infection (IFI) are at
      high risk of developing relapse and fatal complications. Eighteen patients
      affected by hematological malignancies and a previous IFI were submitted to
      allogeneic stem cell transplantation, using Caspofungin as a secondary
      prophylaxis. Patients had a probable or proven fungal infection and 16 had a
      pulmonary localization. No side effects were recorded during treatment with
      Caspofungin. Compared to pre-transplant evaluation, stability or improvement of
      the previous IFI was observed in 16 of the 18 patients at day 30, in 13 of the 15
      evaluable patients at day 180 and in 11 of the 11 evaluable patients at day 360
      post transplant. In particular, all the six patients with a proven fungal
      infection were alive, with a stable or improved IFI after 1 year from transplant.
      At a maximum follow-up of 31 months, eight patients died for disease progression
      or transplant-related complications, but only two had evidence of fungal
      progression. Secondary prophylaxis with Caspofungin may represent a suitable
      approach to limit IFI relapse or progression, allowing patients with
      hematological malignancies to adhere to the planned therapeutic program.

PMID- 17529997
TI  - Outcomes of hematopoietic stem cell transplantation for Hurler's syndrome in
      Europe: a risk factor analysis for graft failure.
AB  - Hurler's syndrome (HS), the most severe form of mucopolysaccharidosis type-I,
      causes progressive deterioration of the central nervous system and death in
      childhood. Allogeneic stem cell transplantation (SCT) before the age of 2 years
      halts disease progression. Graft failure limits the success of SCT. We analyzed
      data on HS patients transplanted in Europe to identify the risk factors for graft
      failure. We compared outcomes in 146 HS patients transplanted with various
      conditioning regimens and grafts. Patients were transplanted between 1994 and
      2004 and registered to the European Blood and Marrow Transplantation database.
      Risk factor analysis was performed using logistic regression. 'Survival' and
      'alive and engrafted'-rate after first SCT was 85 and 56%, respectively. In
      multivariable analysis, T-cell depletion (odds ratio (OR) 0.18; 95% confidence
      interval (CI) 0.04-0.71; P=0.02) and reduced-intensity conditioning (OR 0.08; 95%
      CI 0.02-0.39; P=0.002) were the risk factors for graft failure. Busulfan
      targeting protected against graft failure (OR 5.76; 95% CI 1.20-27.54; P=0.028).
      No difference was noted between cell sources used (bone marrow, peripheral blood
      stem cells or cord blood (CB)); however, significantly more patients who received
      CB transplants had full-donor chimerism (OR 9.31; 95% CI 1.06-82.03; P=0.044).
      These outcomes may impact the safety/efficacy of SCT for 'inborn-errors of
      metabolism' at large. CB increased the likelihood of sustained engraftment
      associated with normal enzyme levels and could therefore be considered as a
      preferential cell source in SCT for 'inborn errors of metabolism'.

PMID- 17529998
TI  - Failure of the addition of methylprednisolone to intermediate-dose
      cyclophosphamide and lenograstim for stem cell mobilization to make the timing of
      PBSC harvesting more predictable.

PMID- 17529999
TI  - Expansion of B cell precursors after unrelated cord blood transplantation for an
      adult patient.

PMID- 17530000
TI  - Autologous hematopoietic stem cell transplantation in peripheral T-cell lymphoma
      using a uniform high-dose regimen.
AB  - The role of high-dose therapy and autologous stem cell transplantation (ASCT) for
      patients with peripheral T-cell lymphoma (PTCL) is poorly defined. Comparisons of
      outcomes between PTCL and B-cell non-Hodgkin's lymphoma (NHL) have yielded
      conflicting results, in part due to the rarity and heterogeneity of PTCL. Some
      retrospective studies have found comparable survival rates for patients with T-
      and B-cell NHL. In this study, we report our single-center experience of ASCT
      over one decade using a uniform chemotherapy-only high-dose regimen. Thirty-two
      patients with PTCL-unspecified (PTCL-u; 11 patients) and anaplastic large-cell
      lymphoma (21 patients) underwent autologous stem cell transplant, mostly for
      relapsed or refractory disease. The preparative regimen consisted of busulfan,
      etoposide and cyclophosphamide. Kaplan-Meier 5-year overall survival (OS) and
      relapse-free survival (RFS) are 34 and 18%, respectively. These results suggest a
      poor outcome for patients with PTCL after ASCT, and new therapies for T-cell
      lymphoma are needed.

PMID- 17530001
TI  - Indiscernible benefit of high-resolution HLA typing in improving long-term
      clinical outcome of unrelated umbilical cord blood transplant.
AB  - The success of allogeneic hematopoietic stem cell transplantation depends in part
      on the accuracy of human leukocyte antigen (HLA) matching between the donor
      recipient pair. The higher the number of matching HLA alleles, the smaller the
      chance that the transplant recipient will develop complications. Umbilical cord
      blood (UCB) transplantation was noted to result in a remarkably low frequency and
      severity of graft-versus-host disease (GvHD) and graft rejection compared to that
      in unrelated bone marrow transplant recipients. At present most banks match UCB
      donors for respective recipients by HLA-A, -B low-resolution typing and -DRB1
      high-resolution typing. We retrospectively conducted high-resolution sequence
      based HLA typing on DNA samples available from 65 Chinese UCB-recipient pairs
      typed previously by using low-resolution sequence-specific oligonucleotide probes
      and sequence-specific primers, and evaluated the clinical outcome. High
      resolution typing revealed imperceptible HLA alleles that were hardly identified
      in low-resolution typing. Univariate analyses demonstrated no significant
      correlation between the extents of high-resolution HLA disparity with
      engraftment, graft failure, acute GvHD, transplant-related mortality and long
      term 6-year overall survival. Data from the study suggest that high-resolution
      typing for HLA-A, -B and -DRB1 contributed no substantial improvement to UCB
      transplant outcome. Low-resolution typing appears to be amenable to matching UCB
      recipient pairs without compromising the quality of transplant.

PMID- 17530002
TI  - Long-term outcomes after allogeneic stem cell transplantation for children with
      hematological malignancies.
AB  - We analyzed long-term outcomes and psycho-social aspects in 112 children with
      malignancies surviving 1 year after hematopoietic stem cell transplantation. At
      10 years, overall survival was 75+/-5%, TRM 18+/-4% and relapse 14+/-3%; 10-year
      cumulative incidence of infections was 31+/-4%, cataract 44+/-4%, pulmonary
      dysfunction 20+/-4%, bone and joint complications 29+/-5%, hypothyroidism 36+/
      4%, cardiac complications 11+/-3% and secondary malignancies 7+/-3%. Total body
      irradiation (TBI) was the most significant risk factor associated with cataract,
      pulmonary impairment, osteoarticular complications and hypothyroidism. Chronic
      graft-versus-host disease was associated with higher incidence of pulmonary
      dysfunction. The number of complications per patient increased with time. Half of
      the patients had psychological disturbance, 13 signs of depression and 16 a
      history of eating behavior disorders; 54% of patients with one or more long-term
      complications had psychological problems. Sixty-nine patients had learning
      difficulties and 36 achieved normal scholarship. With increased follow-up,
      development of late effects and of psycho-social disturbance are of major
      concern. While the use of single-dose TBI has now been abandoned, other risk
      factors are still of concern in the early 2000s.

PMID- 17530003
TI  - Difficult stem cell mobilization despite adequate CD34+ cell dose predicts
      shortened progression free and overall survival after autologous HSCT for
      lymphoma.
AB  - Hematopoietic growth factors alone or in combination with myelosuppressive
      chemotherapy are used to mobilize peripheral blood stem cells for autologous
      transplantation. To identify characteristics of successful mobilization with
      granulocyte colony-stimulating factor (G-CSF) alone and to study the impact of
      immediate chemotherapy mobilization following G-CSF mobilization, we treated 175
      chemotherapy sensitive lymphoma patients with G-CSF (G) mobilization and
      leukapheresis followed by chemotherapy plus G-CSF (CG) mobilization and
      leukapheresis and then autologous transplantation. Patients with stage I/II
      disease at diagnosis and < or =5 years from diagnosis were more likely to
      mobilize successfully with G-CSF alone (G). CG mobilization led to superior stem
      cell yields compared to the preceding mobilization with G (median 2.37 vs 1.37 (
      x 10(6)CD34+ cells/kg); P<0.0001). Patients (n=58, 33%) with successful G-CSF
      mobilization (> or =2 x 10(6) CD34+ cells/kg) had quicker platelet recovery and
      improved progression free and overall survival compared to patients who had
      adequate collection only after chemotherapy mobilization or to those who failed
      to collect an adequate graft with either type of mobilization. The poor clinical
      outcome of patients with difficult mobilization using either method identifies
      them as a high-risk group who might benefit from alternative therapies.

PMID- 17530004
TI  - Relevance of drug allergy history after allogeneic hemopoietic stem cell
      transplantation.

PMID- 17530005
TI  - Antibiotic cycling to decrease bacterial antibiotic resistance: a 5-year
      experience on a bone marrow transplant unit.
AB  - Multidrug-resistant pathogens have important effects on clinical outcomes.
      Antibiotic cycling is one approach to control anti-microbial resistance, but few
      studies have examined cycling in hematology-oncology units. Antibiotic cycling
      was implemented in January 1999 at our hematology-oncology unit, alternating
      piperacillin-tazobactam (pip-tazo) and cefepime in 3 months periods, until June
      2004. Clinical isolates were compared in post- and pre-intervention periods and
      with the susceptibility among the solid organ transplant intensive care unit
      (TICU) isolates. The rate of Gram-negative isolates remained stable. Among Gram
      negatives, susceptibility to cefepime and pip-tazo remained stable. There was an
      increase in Enterococcus spp. (P=0.007), and susceptibility to ampicillin and
      vancomycin decreased (odds ratio (OR): 0.04, 95% confidence interval (CI): 0.17
      0.89 and OR: 0.23, 95% CI: 0.09-0.58). Compared with the TICU, there was
      increased susceptibility to pip-tazo and cefepime among enterics (OR: 7.32, 95%
      CI: 4.44-12.07 and OR: 8.82, 95% CI: 2.1-37.13) and Pseudomonas aeruginosa (OR:
      4.27, 95% CI: 1.47-12.4 and OR: 4.61, 95% CI: 1.75-12.1) and decreased
      susceptibility to ampicillin and vancomycin among enterococci (OR: 0.44, 95% CI:
      0.30-0.63 and OR: 0.38, 95% CI: 0.26-0.56). Cycling was associated with preserved
      antibiotic susceptibility among Gram-negatives, but with an increase in
      Enterococcus spp. and vancomycin and ampicillin resistance among enterococci.

PMID- 17530006
TI  - The presence of functional CCR5 and EBV reactivation after allogeneic
      haematopoietic stem cell transplantation.
AB  - EBV reactivation is a serious complication affecting the recipients of allogeneic
      haematopoietic stem cell transplants (allogeneic HSCT). Recent reports have
      suggested that EBV reactivation induces increased expression of C-C chemokine
      receptor-5 (CCR5) or its ligands. Therefore, the 32-nucleotide deletion within
      the CCR5-encoding gene (CCR5Delta32 polymorphism) was analysed in 92 recipients
      of allogeneic HSCT and their donors and related with EBV load. In addition in 30
      patients, at the same time points employing a real-time PCR technique, the number
      of viral copies and CCR5 transcripts were assessed. The incidence of EBV
      reactivation 2-3 months after transplantation was significantly lower in patients
      carrying the CCR5Delta32 allele (P=0.008). The association was confirmed in
      multivariate analysis, in which recipient CCR5Delta32 (OR=0.166, P=0.026) in
      addition to recipient age (OR=1.536, P=0.034) were identified as independent risk
      factors for EBV reactivation. Moreover, EBV reactivation was more frequently seen
      when patients and their donors were lacking the CCR5 deletion mutation as
      compared to other donor-recipient pairs (P=0.022). The CCR5 expression was
      significantly higher in the group of patients having EBV reactivation than in
      those lacking it (R=25.354, P=0.024). These results suggest that the expression
      of functional CCR5 plays a role in initiation/perpetuation of EBV reactivation.

PMID- 17530007
TI  - Comparable incidence and severity of cytomegalovirus infections following T cell
      depleted allogeneic stem cell transplantation preceded by reduced intensity or
      myeloablative conditioning.
AB  - Reports on infectious complications following reduced intensity conditioning
      (RIC) before allogeneic stem cell transplantation (allo-SCT) are equivocal. This
      prospective follow-up study compared the impact of cytomegalovirus (CMV)
      infections following RIC with fludarabine, ATG and busulphan or conventional
      myeloablative conditioning (MAC). Forty-eight RIC and 59 MAC patients were
      enrolled. The occurrence and severity of CMV infections within 100 days following
      allo-SCT were assessed, using plasma CMV DNA load kinetics. CMV DNAemia was
      observed in 21 RIC (60%) and in 19 MAC (44%) patients at risk for CMV. The mean
      CMV DNAemia free survival time was comparable following RIC and MAC: 70 days (95%
      (confidence interval) CI: 59-80 days) and 77 days (95% CI: 68-86 days),
      respectively (P=0.24). Parameters indicative for the level of CMV reactivation,
      including the area under the curve of CMV DNA load over time as well as the
      onset, the peak values and duration of CMV infection episodes, the numbers and
      duration of CMV treatment episodes and recurrent infections, were not different
      in both groups. During follow-up, none of the patients developed CMV disease. RIC
      with fludarabine, ATG and busulphan demonstrated safety comparable to
      conventional MAC with regard to frequency and severity of CMV infections within
      100 days following T cell-depleted allo-SCT.

PMID- 17530008
TI  - Outpatient allografting using non-myeloablative conditioning: the Mexican
      experience.
AB  - A group of 132 patients with both malignant and nonmalignant conditions was
      allografted using the 'Mexican' method of non-ablative conditioning. The
      conditioning was delivered on an outpatient basis and the procedure was planned
      to be conducted on outpatients in all cases. While 103 patients (78%) were able
      to complete the procedure totally as outpatients, 29 (22%) were hospitalized
      because of fever, mucositis or acute graft-versus-host disease. In a multivariate
      analysis, although differences were not statistically significant, it was found
      that the patients who were allografted as outpatients had higher levels of
      hemoglobin (12 versus 11.8 g/dl), higher platelet counts (248 versus 191 x
      10(9)/l), lower white blood cell counts (11.7 versus 12.4 x 10(9)/l), higher
      Karnofsky scale scores (100 versus 90%) and lower creatinine levels (0.9 versus
      0.93 mg/dl). A total of 86% of the patients with normal values for these
      variables could be allografted as outpatients, whereas only 67% of those with
      abnormal values completed the entire procedure as outpatients. It is concluded
      that allografting can be accomplished totally on an outpatient basis using the
      'Mexican' reduced intensity-conditioning regimen.

PMID- 17530009
TI  - Risk factors associated with late cytomegalovirus reactivation after allogeneic
      stem cell transplantation for hematological malignancies.
AB  - We analyzed the clinical factors associated with late cytomegalovirus (CMV)
      reactivation in a group of 269 consecutive recipients of allogeneic stem cell
      transplant (SCT) for hematological malignancies. Eighty-four subjects (31%)
      experienced late CMV reactivation, including 64 with prior early reactivation and
      20 with isolated late reactivation. Multivariate analyses were conducted in
      patients with early CMV reactivation to identify factors associated with late
      recurrence. Important risk factors included lymphoid diagnosis, occurrence of
      graft-versus-host disease (GVHD), greater number of episodes of early
      reactivation, persistent day 100 lymphopenia and the use of a CMV-seronegative
      donor graft. We combined these risk factors in a predictive model to identify
      those at relatively low, intermediate and high risk. The low-risk group (15%
      cumulative incidence, CI) encompassed patients without early CMV reactivation,
      and subjects transplanted for a myeloid malignancy from a matched-related (MR)
      donor without subsequent acute GVHD. The high-risk patients (73% CI) met all of
      the following criteria: (1) received an MR graft but developed GVHD, or received
      a non-MR graft irrespective of GVHD; (2) had more than two episodes of early
      reactivation; and (3) received a CMV-seronegative graft and/or remained
      persistently lymphopenic at day 100 after SCT. The remaining patients had an
      intermediate incidence of 32%.

PMID- 17530010
TI  - The HLA-A*0201-restricted minor histocompatibility antigen HA-1H peptide can also
      be presented by another HLA-A2 subtype, A*0206.
AB  - HA-1(H) is one of the most attractive minor histocompatibility antigens (mHA) as
      a target for immunotherapy of hematopoietic malignancies, but HLA-A*0201 and HLA
      B60 molecules capable of presenting HA-1(H)-derived peptides are less common in
      eastern Asian populations when compared with Caucasian populations. Therefore, an
      attempt was made to search for novel epitopes presented by HLA alleles other than
      those previously reported by generating CTL lines from patients undergoing HLA
      identical, HA-1 disparate hematopoietic stem cell transplantation (hematopoietic
      SCT) by stimulation with a 29-mer HA-1(H) peptide spanning a central polymorphic
      histidine (His). Two CTL clones established were found to be restricted by HLA
      A*0206, which is the second or third most common HLA-A2 subtype worldwide.
      Epitope mapping revealed that the clones recognized the same nonameric peptide as
      A*0201-restricted HA-1(H), VLHDDLLEA. This epitope was unexpected, since it does
      not contain any preferred anchor motifs for HLA-A*0206. However, an HLA peptide
      binding assay revealed stronger binding of this peptide to A*0206 than to A*0201.
      Interestingly, HLA-A*0206-restricted CTL clones could lyse both HLA-A*0206(+) and
      HLA-A*0201(+) targets (including leukemic blasts) that express HA-1(H) peptide
      endogenously, whereas an HLA-A*0201-restricted, HA-1(H)-specific CTL clone failed
      to lyse HLA-A*0206(+) targets. This finding will expand the patient population
      who can benefit from HA-1(H)-based immunotherapy.

PMID- 17530012
TI  - Preface: antibody therapies for cancer.

PMID- 17530013
TI  - Anti-idiotype antibodies in cancer treatment.
AB  - As a cancer immunotherapy tool, idiotypes (Ids) have been used in different ways
      over the last three decades, depending on the actual human tumor cell target. It
      all started with passive, monoclonal, anti-Id antibody treatment of B-cell
      lymphoma, a setting in which results were tantalizing, but logistics
      unsustainable. It then moved toward the development of anti-Id vaccines for the
      treatment of the same tumors, a setting in which we have recently provided the
      first formal proof of principle of clinical benefit associated with the use of a
      human cancer vaccine. Meanwhile, it also expanded in the direction of exploiting
      the antigenic mimicry of some Ids with Id-unrelated, tumor-associated antigens
      for the immunotherapy of a number of solid tumors, a setting in which clinical
      results are still far from being consolidated. All in all, over the years Id
      based immunotherapy has paved the way for a number of seminal therapeutic
      improvements for cancer patients, including the development of most if not all Id
      unrelated monoclonal antibodies that have recently revolutionized the field.

PMID- 17530014
TI  - Rituximab therapy in malignant lymphoma.
AB  - Rituximab is the first monoclonal antibody to have been registered for the
      treatment of B-cell lymphomas. Randomized studies have demonstrated its activity
      in follicular lymphoma (FL), mantle cell lymphoma and diffuse large B-cell
      lymphoma (DLBCL) in untreated or relapsing patients. Non-comparative studies have
      shown an activity in all other lymphomas. Because of its high activity and low
      toxicity ratio, rituximab has transformed the outcome of patients with B-cell
      lymphoma. A combination of rituximab plus chemotherapy,
      rituximab+cyclophosphamide+doxorubicin+vincristine+prednisolone (R-CHOP), has the
      highest efficacy ever described with any chemotherapy in DLBCL and FL. Some
      patients are refractory to rituximab but the precise mechanisms of this
      refractoriness are not understood.

PMID- 17530015
TI  - Radioimmunotherapy for B-cell lymphoma: Y90 ibritumomab tiuxetan and I(131)
      tositumomab.
AB  - Radioimmunotherapy, targeting the CD20 antigen, in B-cell lymphoma has clearly
      demonstrated efficacy and tolerability over the preceding 15 years. As a result,
      two products are available with Food and Drug Administration approval for
      marketing - Y(90) ibritumomab tiuxetan and I(131) tositumomab, given as the
      Zevalin and Bexxar therapeutic regimens, respectively. Both demonstrate high
      response rates and durability of remission in the relapsed/refractory disease
      setting. Data are emerging regarding their utility as initial therapy, and
      furthermore, they are been investigated for use sequentially with chemotherapy,
      and in the myeloablative setting. As yet however, how to best use these agents in
      the clinical disease course remains uncertain.

PMID- 17530016
TI  - Rituximab-induced inhibition of antiapoptotic cell survival pathways:
      implications in chemo/immunoresistance, rituximab unresponsiveness, prognostic
      and novel therapeutic interventions.
AB  - Rituximab (chimeric anti-CD20 monoclonal antibody) is the first Food and Drug
      Administration approved antitumor antibody and is used in the treatment of B-non
      Hodgkin's lymphoma (B-NHL). It is used as single monotherapy or in combination
      with chemotherapy and has improved the treatment outcome of patients with B-NHL.
      The in vivo mechanisms of rituximab-mediated antitumor effects include antibody
      dependent cellular cytotoxicity (ADCC), complement-dependent cell cytotoxicity
      (CDC), growth-inhibition and apoptosis. A subset of patients does not initially
      respond to rituximab and several responsive patients develop resistance to
      further rituximab treatment. The mechanism of rituximab unresponsiveness is not
      known. Besides the above-postulated mechanisms, rituximab has been shown to
      trigger the cells via CD-20. Studies performed with B-NHL cell lines as model
      systems revealed several novel mechanisms of rituximab-mediated effects that are
      involved in chemo/immunosensitization and the development of resistance to
      rituximab. Rituximab has been shown to inhibit the p38 mitogen-activated protein
      kinase, nuclear factor-kappaB (NF-kappaB), extracellular signal-regulated kinase
      1/2 (ERK 1/2) and AKT antiapoptotic survival pathways, all of which result in
      upregulation of phosphatase and tensin homolog deleted on chromosome ten and Raf
      kinase inhibitor protein and in the downregulation of antiapoptotic gene products
      (particularly Bcl-2, Bcl-(xL) and Mcl-1), and resulting in
      chemo/immunosensitization. Further, rituximab treatment inhibits the
      overexpressed transcription repressor Yin Yang 1 (YY1), which negatively
      regulates Fas and DR5 expression and its inhibition leads to sensitization to Fas
      ligand and tumor necrosis factor-related apoptosis-inducing ligand-induced
      apoptosis. Rituximab-resistant clones were generated as model to examine the
      mechanism of in vivo rituximab unresponsiveness. These clones showed reduced
      expression of CD20 and hyperactivation of the above antiapoptotic signaling
      pathways and failure of rituximab to trigger the cells leading to inhibition of
      ADCC, CDC and chemo/immunosensitization. Interference with the hyperactivated
      pathways with various pharmacological and proteasome inhibitors reversed
      resistance. Furthermore, the above findings have identified several gene products
      that can serve as new prognostic/diagnostic biomarkers as well as targets for
      therapeutic intervention in B-NHL.

PMID- 17530017
TI  - Trastuzumab: triumphs and tribulations.
AB  - The human epidermal growth factor receptor 2 (HER2) tyrosine kinase receptor is
      overexpressed in approximately 20-30% of human breast cancers, and is associated
      with reduced survival. Hence, numerous therapeutic strategies have been tested
      for their ability to target the HER2 protein. The humanized monoclonal antibody
      trastuzumab (Herceptin) was the first HER2-targeted agent approved for clinical
      use in breast cancer patients. Response rates to single-agent trastuzumab range
      from 12 to 34% for metastatic breast cancer (MBC), and significant improvements
      in survival rates are achieved in patients with early-stage HER2-overexpressing
      breast cancer in the adjuvant setting. Despite its initial efficacy, acquired
      resistance to trastuzumab develops in a majority of patients with MBC, and a
      large subset never responds, demonstrating primary resistance. Molecular
      mechanisms of trastuzumab antineoplastic activity and potential mechanisms
      contributing to its resistance will be discussed in this review. Novel agents
      that may enhance trastuzumab efficacy will also be discussed.

PMID- 17530018
TI  - Alemtuzumab (Campath-1H) in the treatment of chronic lymphocytic leukemia.
AB  - Alemtuzumab (Campath-1H) is a humanized IgG1 monoclonal antibody that targets the
      human CD52 antigen. CD52 is expressed by a variety of lymphoid neoplasms and most
      human mononuclear cell subsets. In 2001, alemtuzumab was approved for marketing
      in the United States and Europe for use in patients with fludarabine-refractory
      chronic lymphocytic leukemia (CLL). In heavily pretreated patients with CLL, the
      overall response rate (ORR) is approximately 35%, and in previously untreated
      patients the ORR is greater than 80%, with a recent randomized study suggesting
      it is superior to alkylator-based therapy. Importantly, alemtuzumab is effective
      in patients with high-risk del(17p13.1) and del(11q22.3) CLL. Alemtuzumab
      combination studies with fludarabine and/or monoclonal antibodies such as
      rituximab have demonstrated promising results. Alemtuzumab is also being studied
      in CLL patients as consolidation therapy for treatment of minimal residual
      disease, in preparation for stem cell transplantation and to prevent acute and
      chronic graft versus host disease. Alemtuzumab is frequently associated with
      acute 'first-dose' reactions when administered intravenously, but is much better
      tolerated when administered subcutaneously without loss of therapeutic efficacy.
      Additional potential adverse events associated with alemtuzumab administration
      include myelosuppression as well as profound cellular immune dysfunction with the
      associated risk of viral reactivation and other opportunistic infections.
      Additional studies detailing the mechanism of action of alemtuzumab as well as
      new strategies for prevention of opportunistic infections will aid in the future
      therapeutic development of this agent.

PMID- 17530019
TI  - Cetuximab, a chimeric human mouse anti-epidermal growth factor receptor
      monoclonal antibody, in the treatment of human colorectal cancer.
AB  - The recent successful development of monoclonal antibodies that target key
      components of biological pathways has expanded the armamentarium of treatment
      options for patients with colorectal cancer (CRC). In particular, the epidermal
      growth factor receptor (EGFR), a tyrosine kinase growth factor receptor involved
      in CRC development and progression, is exploited by the newest monoclonal
      antibody that is available for use in CRC patients. Cetuximab, the first chimeric
      monoclonal antibody, which has been generated against the EGFR, is currently
      registered in USA, Europe and worldwide, in combination with irinotecan in the
      treatment of metastatic CRC patients who have progressed on irinotecan containing
      chemotherapy. Cetuximab is well tolerated and does not exacerbate the toxicity of
      concomitant chemotherapy. Furthermore, a series of phase III clinical trials are
      currently evaluating the combination of cetuximab with standard chemotherapy
      regimens in the first-line treatment chemotherapy-naive patients with metastatic
      CRC.

PMID- 17530020
TI  - Current role of antibody therapy in patients with metastatic colorectal cancer.
AB  - In less than 10 years, the number and importance of non-surgical treatment
      modalities in patients with colorectal cancer (CRC) have increased dramatically,
      both in the adjuvant and the advanced settings. However, despite the improvement
      of cytotoxic therapy in CRC, many patients still develop progressive disease and
      unfortunately in patients with disease resistant to 5-fluorouracil/folinic acid,
      irinotecan and oxaliplatin, no effective cytotoxic therapy is known. The rapidly
      expanding knowledge in tumor biology has encouraged optimism for the possibility
      to find and target tumor-specific mechanisms and thereby increase both efficacy
      and tolerance. A great number of 'targeted drugs' are being tested in clinical
      trials and some of these new drugs, like bevacizumab, cetuximab and panitumumab,
      are available for routine use in health care. These new targeted drugs will
      expand the therapeutic arsenal in CRC to a great extent, but they will also add
      to the complexity of treatment of CRC. In this review, we summarize the current
      status of antibody therapy in patients with CRC.

PMID- 17530021
TI  - The role of Gemtuzumab Ozogamicin in the treatment of acute myeloid leukemia
      patients.
AB  - Gemtuzumab Ozogamicin (GO) is an antibody-targeted chemotherapy agent consisting
      of the humanized murine CD33 antibody (clone P67.6) to which the calicheamicin-g1
      derivative is attached via a hydrolysable bifunctional linker. GO is able to
      induce apoptosis in vitro in CD33-expressing cells and it has been approved in
      USA and in Europe as monotherapy for the treatment of elderly patients (older
      than 60 years) with relapsed acute myeloid leukemia (AML). GO administered as a
      single agent has resulted in overall response rates of about 30% in previously
      relapsed adults AML patients (including also with incomplete platelet recovery).
      Preliminary data indicate a potential role for GO also as a component of
      induction or consolidation regimens in adults and children. As for adverse
      events, veno-occlusive syndrome characterizes its tolerability profile, but GO is
      comparatively well tolerated by most patients.

PMID- 17530022
TI  - Bevacizumab in the treatment of non-small-cell lung cancer.
AB  - Lung cancer is the leading cause of cancer death in the United States. The
      majority of patients present with advanced disease, and treatment with standard
      cytotoxic chemotherapy improves survival and quality of life in patients with a
      preserved functional status. However, the prognosis is poor with the majority of
      patients dying in less than a year. Treatment with standard cytotoxic
      chemotherapy has reached a therapeutic plateau, and new therapeutic approaches
      have investigated therapies that target the specific molecular pathways involved
      in carcinogenesis and angiogenesis. The most promising strategy for inhibiting
      angiogenesis involves agents that either target the proangiogenesis growth
      factor, vascular endothelial growth factor A (VEGF) by preventing binding to the
      receptor or inhibiting the downstream signaling of the vascular endothelial
      growth factor receptor. The only therapeutic agent approved for the treatment of
      lung cancer is bevacizumab, a monoclonal antibody that binds to VEGF. A recent
      phase III trial revealed a statistically significant improvement in response
      rate, progression free and overall survival with combination of bevacizumab with
      chemotherapy over chemotherapy alone. Attempts to identify surrogate markers of
      antiangiogenesis activity are currently ongoing, and may assist in the selection
      of patients for antiangiogenesis therapy and the development of this class of
      agents.

PMID- 17530023
TI  - Daclizumab (anti-Tac, Zenapax) in the treatment of leukemia/lymphoma.
AB  - Daclizumab (Zenapax) identifies the alpha subunit of the interleukin-2 (IL-2)
      receptor and blocks the interaction of this cytokine with its growth factor
      receptor. The scientific basis for the choice of the IL-2 receptor alpha subunit
      as a target for monoclonal antibody-mediated therapy of leukemia/lymphoma is that
      very few normal cells express IL-2R alpha, whereas the abnormal T cells in
      patients with an array of lymphoid malignancies express this receptor. In 1997,
      daclizumab was approved by the FDA for use in the prevention of renal allograft
      rejection. In addition, anti-Tac provided effective therapy for select patients
      with T-cell malignancies and an array of inflammatory autoimmune disorders.
      Finally, therapy with this antibody armed with (90)Y has led to clinical
      responses in the majority of patients with adult T-cell leukemia. These insights
      concerning the IL-2/IL-2 receptor system facilitated the development of effective
      daclizumab antibody therapy for select patients with leukemia/lymphoma.

PMID- 17530024
TI  - Preclinical and clinical evaluation of epratuzumab (anti-CD22 IgG) in B-cell
      malignancies.
AB  - The vast majority of non-Hodgkin's lymphomas are of B-cell phenotype. Development
      of unlabeled or radiolabeled therapeutic monoclonal antibodies against the cell
      surface antigen, CD20, has revolutionized the treatment of these malignancies. It
      is clear that antibodies targeting other B-cell-specific molecules, such as CD22,
      also offer potential therapeutic benefit. Epratuzumab is a humanized anti-CD22
      monoclonal, which has undergone preclinical and phase I/II clinical evaluation in
      patients with indolent or aggressive lymphoma. Data suggest that this agent is
      well tolerated, and can induce tumor regressions. Trials are currently evaluating
      its safety and activity in combination with rituximab (chimeric anti-CD20) and
      standard chemotherapy are ongoing. Initial results suggest that these regimens
      have acceptable toxicity, and that epratuzumab warrants further evaluation as an
      adjunct to standard lymphoma treatment regimens.

PMID- 17530025
TI  - Novel antibodies as anticancer agents.
AB  - In recent years antibodies, whether generated by traditional hybridoma technology
      or by recombinant DNA strategies, have evolved from Paul Ehrlich's 'magic
      bullets' to a modern age 'guided missile'. In the recent years of immunologic
      research, we are witnessing development in the fields of antigen screening and
      protein engineering in order to create specific anticancer remedies. The
      developments in the field of recombinant DNA, protein engineering and cancer
      biology have let us gain insight into many cancer-related mechanisms. Moreover,
      novel techniques have facilitated tools allowing unique distinction between
      malignantly transformed cells, and regular ones. This understanding has paved the
      way for the rational design of a new age of pharmaceuticals: monoclonal
      antibodies and their fragments. Antibodies can select antigens on both a specific
      and a high-affinity account, and further implementation of these qualities is
      used to target cancer cells by specifically identifying exogenous antigens of
      cancer cell populations. The structure of the antibody provides plasticity
      resonating from its functional sites. This review will screen some of the many
      novel antibodies and antibody-based approaches that are being currently developed
      for clinical applications as the new generation of anticancer agents.

PMID- 17530026
TI  - Novel radiolabeled antibody conjugates.
AB  - This article reviews the development of radioimmunoconjugates as a new class of
      cancer therapeutics. Numerous conjugates involving different antigen targets,
      antibody forms, radionuclides and methods of radiochemistry have been studied in
      the half-century since radioactive antibodies were first used in model systems to
      selectively target radiation to tumors. Whereas directly conjugated antibodies,
      fragments and subfragments have shown promise preclinically, the same approaches
      have not gained success in patients except in radiosensitive hematological
      neoplasms, or in settings involving minimal or locoregional disease. The
      separation of tumor targeting from the delivery of the therapeutic radionuclide
      in a multistep process called pretargeting has the potential to overcome many of
      the limitations of conventional, or one-step, radioimmunotherapy, with initial
      preclinical and clinical data showing increased sensitivity, specificity and
      higher radiation doses delivered. Our particular focus in pretargeting is the use
      of bispecific, trimeric (three Fab's) constructs made by a new antibody
      engineering method termed 'dock-and-lock.

PMID- 17530027
TI  - Targeting death-inducing receptors in cancer therapy.
AB  - Deregulated cell death pathways may lead to the development of cancer, and
      induction of tumor cell apoptosis is the basis of many cancer therapies.
      Knowledge accumulated concerning the molecular mechanisms of apoptotic cell death
      has aided the development of new therapeutic strategies to treat cancer. Signals
      through death receptors of the tumor necrosis factor (TNF) superfamily have been
      well elucidated, and death receptors are now one of the most attractive
      therapeutic targets in cancer. In particular, DR5 and DR4, death receptors of TNF
      related apoptosis-inducing ligand (TRAIL or Apo2L), are interesting targets of
      antibody-based therapy, since TRAIL may also bind decoy receptors that may
      prevent TRAIL-mediated apoptosis, whereas TRAIL ligand itself selectively induces
      apoptosis in cancer cells. Here, we review the potential therapeutic utility of
      agonistic antibodies against DR5 and DR4 and discuss the possible extension of
      this single-antibody-based strategy when combined with additional modalities that
      either synergizes to cause enhanced apoptosis or further engage the cellular
      immune response. Rational design of antibody-based therapies combining the
      induction of tumor cell apoptosis and activation of tumor-specific adaptive
      immunity enables promotion of distinct steps of the antitumor immune response,
      thereby enhancing tumor-specific lymphocytes that can eradicate TRAIL/DR5
      resistant mutating, large established and heterogeneous tumors in a manner that
      does not require the definition of individual tumor-specific antigens.

PMID- 17530028
TI  - Antibody-targeted vaccines.
AB  - The specificity and high affinity binding of antibodies provides these molecules
      with ideal properties for delivering a payload to target cells. This concept has
      been commercialized for cancer therapies using toxin- or radionucleotide
      conjugated antibodies that are designed to selectively deliver cytotoxic
      molecules to cancer cells. Exploiting the same effective characteristics of
      antibodies, antibody-targeted vaccines (ATV) are designed to deliver disease
      specific antigens to professional antigen-presenting cells (APCs), thus enabling
      the host's immune system to recognize and eliminate malignant or infected cells
      through adaptive immunity. The concept of ATVs has been in development for many
      years, and recently has entered clinical trials. Early studies with ATVs focused
      on the ability to induce humoral immunity in the absence of adjuvants. More
      recently, ATVs targeted to C-type lectin receptors have been exploited for
      induction of potent helper and cytolytic T-cell responses. To maximize their
      stimulatory capacity, the ATVs are being evaluated with a variety of adjuvants or
      other immunostimulatory agents. In the absence of co-administered
      immunostimulatory signals, APC-targeting can induce antigen-specific tolerance
      and, thus, may also be exploited in developing specific treatments for autoimmune
      and allergic diseases, or for preventing transplant rejection. The successful
      clinical application of this new class of antibody-based products will clearly
      depend on using appropriate combinations with other strategies that influence the
      immune system.

PMID- 17530029
TI  - 'Tissue surrogates' as a model for archival formalin-fixed paraffin-embedded
      tissues.
AB  - High-throughput proteomic studies of archival formalin-fixed paraffin-embedded
      (FFPE) tissues have the potential to be a powerful tool for examining the
      clinical course of disease. However, advances in FFPE tissue-based proteomics
      have been hampered by inefficient methods to extract proteins from archival
      tissue and by an incomplete knowledge of formaldehyde-induced modifications in
      proteins. To help address these problems, we have developed a procedure for the
      formation of 'tissue surrogates' to model FFPE tissues. Cytoplasmic proteins,
      such as lysozyme or ribonuclease A, at concentrations approaching the protein
      content in whole cells, are fixed with 10% formalin to form gelatin-like plugs.
      These plugs have sufficient physical integrity to be processed through graded
      alcohols, xylene, and embedded in paraffin according to standard histological
      procedures. In this study, we used tissue surrogates formed from one or two
      proteins to evaluate extraction protocols for their ability to quantitatively
      extract proteins from the surrogates. Optimal protein extraction was obtained
      using a combination of heat, a detergent, and a protein denaturant. The addition
      of a reducing agent did not improve protein recovery; however, recovery varied
      significantly with pH. Protein extraction of >80% was observed for pH 4 buffers
      containing 2% (w/v) sodium dodecyl sulfate (SDS) when heated at 100 degrees C for
      20 min, followed by incubation at 60 degrees C for 2 h. SDS-polyacrylamide gel
      electrophoresis of the extracted proteins revealed that the surrogate extracts
      contained a mixture of monomeric and multimeric proteins, regardless of the
      extraction protocol employed. Additionally, protein extracts from surrogates
      containing carbonic anhydrase:lysozyme (1:2 mol/mol) had disproportionate
      percentages of lysozyme, indicating that selective protein extraction in complex
      multiprotein systems may be a concern in proteomic studies of FFPE tissues.

PMID- 17530030
TI  - Activin receptor-like kinase 1 is essential for placental vascular development in
      mice.
AB  - Activin receptor-like kinase 1 (ALK1) is involved in the pathogenesis of
      hereditary hemorrhagic telangiectasia type II (HHT2) and pulmonary arterial
      hypertension. We have previously shown that Alk1 is predominantly expressed in
      the arterial endothelium and plays a pivotal role in the formation of embryonic
      blood vessels. At present, however, little is known about the precise expression
      pattern and function of ALK1 during extra-embryonic vascular development. Using
      previously generated lacZ reporter lines, we sought to examine the expression
      pattern and role of Alk1 during placental development in mice. Alk1 expression
      was restricted to endothelial cells of fetal vessels from the emergence of
      chorioallantoic fusion to the late gestational period, and no detectable Alk1
      expression was observed in syncytiotrophoblasts or spongiotrophoblasts.
      Predominant arterial expression was observed in the umbilical and fetal placental
      vessels as well as in embryonic vessels. Morphological analysis of Alk1-null
      embryos indicates that Alk1 is essential for the development of distinct
      umbilical arteries and veins. The invasion of chorioallantoic mesoderm into the
      forming labyrinth layer was largely unaffected in the Alk1-null placenta, but
      chorioallantoic vessels appeared to be severely dilated and fused. Results from
      this study provide valuable information regarding the role of ALK1 in the
      development of placental vasculature as well as insights into the pathogenesis of
      HHT.

PMID- 17530031
TI  - Glucose modulates handling of apoptotic cells by mesangial cells: involvement of
      TGF-beta1.
AB  - Glucose stimulates proapoptotic signalling pathways in mesangial cells. Studies
      focused on inflammatory glomerular injury have demonstrated that removal of
      apoptotic mesangial cells occurs by neighbouring non-apoptotic mesangial cells.
      The aim of this study was to define the effect of ambient glucose concentration
      on mesangial handling of apoptotic cells, and in addition to examine the response
      made by the mesangial cell. We used a co-culture model in which neutrophils aged
      overnight to induce apoptosis, or apoptotic mesangial cells, labelled with a
      fluorescent dye, were added to mesangial cells to study phagocytosis. Exposure of
      mesangial cells to an ambient glucose concentration of 25 mM D-glucose before
      addition of apoptotic cells led in an increase in mesangial cell phagocytosis.
      Ingestion of apoptotic cells was inhibited by blocking alpha v beta 3 integrin
      vitronectin receptor or thrombospondin-1. Furthermore, glucose-dependent
      stimulation of phagocytosis was inhibited by a blocking antibody to TGF-beta1. Co
      culture of apoptotic cells with mesangial cells stimulated synthesis of TGF-beta1
      as compared to freshly isolated neutrophils. Increased TGF-beta1 synthesis was
      dependent on direct contact between the two cell types but was not dependent on
      phagocytosis of apoptotic cells, as TGF-beta1 generation was not affected by
      inhibition of the thrombospondin-1 pathway. We propose a model in which apoptotic
      cell binding but not phagocytosis stimulates enhanced mesangial cell TGF-beta1
      synthesis. Furthermore phagocytosis, which involves the thrombospondin-1 pathway,
      is uncoupled from binding of apoptotic cells, which stimulated TGF-beta1
      synthesis.

PMID- 17530032
TI  - [Daptomycin. Reassessment of an antibiotic].

PMID- 17530033
TI  - [Tigecycline, the first of a new class of antibiotics: the glycylcyclines].

PMID- 17530034
TI  - [Treatment of infections associated with neurosurgical procedures].

PMID- 17530035
TI  - [Variability in the antibiotics prescription in the Avila Province].
AB  - This study analyzed the consumption of systemic antibiotics in the province of
      Avila, Spain, and its Basic Health Areas (ZBS) during 2005. It was a
      retrospective observational study of the consumption of systemic antibiotics (ATC
      class J01) during 2005 using the data collected by the Concylia program. The
      study population was identified from the 2005 Medical Card Register database.
      Consumption data was expressed in defined daily doses (DDD) per 1,000 inhabitants
      per day (DID), calculated in relation to the contribution of the user at the time
      of acquiring the prescription. It was found that antibiotic consumption in the
      province of Avila in 2005 was 26.91 DHDAj. There was a considerable difference
      between rural (36.63) and urban areas (15.44) with a large variability among the
      different Basic Health Areas. The areas with a smaller number of inhabitants per
      town or city and per doctor, used more antibiotics, which could be due to more
      severe pathology, absence of self-medication or lack of diagnostic resources,
      among other factors. There is no relation between greater consumption and
      workload. It was concluded that the consumption of antibiotics in the province of
      Avila is high due to their use in rural areas. A high variability in the
      consumption of antibiotics was observed between the different areas, which was
      related to the smaller number of inhabitants per city or town and per doctor, but
      had no relation to workload.

PMID- 17530036
TI  - Pharmacokinetic/pharmacodynamic serum and urine profile of cefditoren following
      single-dose and multiple twice- and thrice-daily regimens in healthy volunteers:
      a phase I study.
AB  - The objectives of this randomized, double-blind study were to evaluate the
      pharmacokinetics, and the pharmacodynamic and gastrointestinal (GI) tolerance of
      cefditoren pivoxil in healthy adult male volunteers when it is administered three
      times a day. Twenty healthy volunteers were included in the study. On day 1, 10
      subjects received a 200-mg single dose of cefditoren pivoxil and 10 received a
      400-mg dose. After a washout period of 8 days, eight subjects received cefditoren
      pivoxil 400 mg b.i.d., eight received 400 mg t.i.d., and four received placebo
      for 10 days. Medication was taken 30 min after meals. Blood and urine collections
      were carried out on days 1, 9, 14 and 19. Volunteers were asked about any GI
      change, especially about bowel habits, nausea, vomiting and abdominal pain. The
      maximum cefditoren concentration (C(max)) had a mean value of 3.77+/-0.66 mg/l,
      and was reached between 1.5 and 3 h in the thrice-daily administration. In the
      twice-daily regimen, the C(max) was 3.27+/-0.64 mg/l. The mean time above
      breakpoint minumum inhibitory concentration (MIC), calculated with data from each
      pharmacokinetic profile, was always above 40%, in both the twice- and thrice
      daily regimens. The half-life of cefditoren was 1.19+/-0.2 h and 1.36+/-0.2 h in
      the twice-daily and thrice-daily regimens, respectively. The C(max) of cefditoren
      in urine was reached between 2 and 4 h postadministration, with a mean value of
      154.53 mg/l in the twice-daily regimen, and 186.59 mg/l in the thrice-daily
      administration. There were no differences between the groups in the incidence of
      GI adverse events. The present data show that the administration of cefditoren
      pivoxil 400 mg t.i.d. is possible because it is well tolerated, and it increases
      the probability of success when the MIC of the causative bacteria is close to the
      susceptibility breakpoint. The high concentrations of active drug in the urine
      enable cefditoren to be considered as a useful candidate for the treatment of
      uncomplicated urinary tract infections (UTIs).

PMID- 17530037
TI  - Odontogenic bacteria in periodontal disease and resistance patterns to common
      antibiotics used as treatment and prophylaxis in odontology in Spain.
AB  - Resistance in streptococci or Gram-negative bacteria is associated with
      antibiotic consumption. Scarce information exists on the antibiotic
      susceptibility of bacterial isolates from patients with periodontitis in
      countries with high antibiotic consumption, as this is an area in which
      microbiological testing is not performed in daily practice. The present study was
      undertaken to explore the susceptibility of bacterial isolates in periodontitis
      to antibiotics prescribed in odontology in Spain as treatment for local
      infections or prophylaxis for distant focal infections. Periodontal samples were
      prospectively collected in 48 patients classified by pocket depth of <4 mm and
      >or=4 mm. Species were identified by culture, selecting the five most frequent
      morphotypes per sample, and polymerase chain reaction (PCR). Susceptibility was
      determined by E-test. A total of 261 isolates were identified: 72.9% patients had
      Streptococcus oralis; 70.8% Streptococcus mitis; 60.4% Prevotella buccae; 39.6%
      Prevotella denticola; 37.5% Fusobacterium nucleatum; 35.4% Prevotella intermedia;
      25% Capnocytophaga spp.; 23% Veillonella spp.; 22.9% Prevotella melaninogenica
      and Streptococcus sanguis; and <20% other species. Streptococcus viridans
      resistance rates were 0% for amoxicillin, approximately 10% for clindamycin, 9
      22% for tetracycline, and for azithromycin ranged from 18.2% for S. sanguis to
      47.7% for S. mitis. Prevotella isolates were susceptible to amoxicillin
      clavulanic acid, with amoxicillin resistance ranging from 17.1% in P. buccae to
      26.3% in P. denticola. Metronidazole resistance was <6% in all Prevotella
      species, while clindamycin resistance ranged from 0 to 21.1%. beta-Lactamase
      production was positive in 54.1% Prevotella spp., 38.9% F. nucleatum, 30%
      Capnocytophaga spp., and 10% Veillonella spp. In this study, amoxicillin
      clavulanic acid was the most active antibiotic against all species tested,
      followed by metronidazole in the case of anaerobes.

PMID- 17530038
TI  - Antimicrobial susceptibility of clinical Escherichia coli isolates from
      uncomplicated cystitis in women over a 1-year period in Spain.
AB  - High usage of antibiotics in Spain has led to an increase in resistance in
      urinary Escherichia coli isolates in different geographic regions. The problem of
      resistance in urinary E. coli in Spain was investigated by gathering a large
      number of isolates from 20 different sites nationwide over a 1-year period from
      November 2003 to October 2004 in a large population of women. The objectives of
      this study were to assess the resistance to the antibiotics most commonly
      prescribed for community-acquired urinary tract infections (UTIs), according to
      age and different geographical areas of Spain, and to evaluate the potential
      association between geographical differences in quinolone consumption and
      resistance to E. coli. A total of 2,292 valid E. coli strains from female
      outpatients were isolated and sent to a single central reference laboratory for
      confirmation and susceptibility testing. Of these, 2,230 isolates were available
      for the age analysis. A two-sided chi2 test was used to identify differences in
      resistance between age groups. Antibiotic units per province were purchased from
      IMS and consumption was expressed in units per 1,000 people per year. Univariate
      correlation (Pearson coefficient) between resistance to ciprofloxacin and
      quinolone consumption was calculated using a two-sided p-value. Resistance shown
      by E. coli was more common to ampicillin (52.1%) and cotrimoxazole (26%),
      followed by quinolones (18%), whereas resistance to amoxicillin-clavulanic acid,
      cefuroxime-axetil and fosfomycin was less than 3%. In the subgroup of women aged
      >65 years, resistance to ciprofloxacin was 29% compared to 13% for the subgroup
      of women <65 years (p<0.001). For these same subgroups, resistance rates were 32%
      vs. 23% for cotrimoxazole (p<0.001) and 56% vs. 50% for ampicillin (p=0.02),
      respectively. Statistically significant correlations were found between
      consumption of quinolones and E. coli resistance to ciprofloxacin (r=0.5;
      p=0.025). Resistance of E. coli isolates to quinolones varied significantly
      according to geographical areas, ranging from a high of 16.5% and 16.6% in the
      southern and eastern regions of Spain, respectively, to a low of 8% in the north
      in women aged <65 years. Additionally, the susceptibility to quinolones of E.
      coli isolates recovered from women aged >65 years was significantly lower across
      all regions of Spain than that of isolates recovered from younger women.
      Fosfomycin, amoxicillin/clavulanic acid and cefuroxime-axetil are the most
      suitable antibiotics for empirical treatment in Spain given the high 18% and 26%
      resistance rates to quinolones and cotrimoxazole, respectively. Higher resistance
      rates to ciprofloxacin were associated with being aged 65 years and over. These
      data need to be considered when recommending empirical therapy for acute
      cystitis.

PMID- 17530039
TI  - [Consensus document on the antimicrobial treatment of diabetic-foot infections].

PMID- 17530040
TI  - [Third consensus document on the use of antimicrobial agents in chronic
      obstructive pulmonary disease exacerbations].

PMID- 17530041
TI  - Antiviral, antifungal and antiprotozoal agents in the cinema.
AB  - Among the antimicrobial agents, antibacterials are the most frequently mentioned
      in cinematographic plots. Nevertheless, it is not uncommon to come across other
      antiviral agents, especially antiretrovirals and antiprotozoals. We analyzed the
      presence of antiviral and antifungal agents in different commercial films, both
      when they were merely mentioned in passing and when they played a major role in
      the film. This review essentially aims to address the historical portrayal of
      these agents in film and to list their appearances. The fictional treatments that
      appear in some films are not addressed.

PMID- 17530042
TI  - [Does vaccination affect the prescription of antibiotics?].

PMID- 17530043
TI  - [New anti-pneumococcal vaccines. Beyond pneumococcus].

PMID- 17530044
TI  - [Clinical and therapeutic changes in otitis with anti-pneumococcal vaccination].

PMID- 17530045
TI  - [Immunization and antimicrobials. Is there an association between the effects
      against Streptococcus pneumoniae?].

PMID- 17530046
TI  - [Repercussion of anti-pneumococcal vaccine in resistances].

PMID- 17530047
TI  - [Criteria for introducing new vaccines into the vaccination calendar].

PMID- 17530048
TI  - [Considerations on pediatric pneumococcal infection in Navarra].

PMID- 17530049
TI  - [Conclusions].

PMID- 17530050
TI  - Reasons for placement and replacement of direct restorative materials in Brazil.
AB  - OBJECT: The aim of this study was to report the reasons for placement and
      replacement of direct restorations in private general dental practices in Brazil.
      METHOD AND MATERIALS: Thirty-seven practitioners recorded information regarding
      16 consecutive direct restorations placed by themselves in a 4-week period. The
      information recorded reported the patient's age, gender, tooth number, the class
      of restorations, the restorative material used, and the reasons for placement and
      replacement of amalgam and tooth-colored restorations. The data were
      statistically analyzed through chi-square tests. RESULTS: The average age of the
      patients was 37 years, with female patients occurring more frequently. Of all the
      restorations placed (n = 551), 39.75% were first-time placements, while 60.25%
      were replacements. For first-time restorations, the primary reason for placement
      was primary caries, followed by noncarious tooth substance loss. For amalgam
      restorations, the main reason for replacement was to obtain improved esthetic
      appearance with a tooth-colored material. For restorations of resin composite,
      secondary caries was the principal reason of failure. The resin composite was
      statistically (P <.01) the most indicated material (88.93%) for the placement and
      replacement of restorations. CONCLUSION: Replacements have been the main reason
      for performing direct restorations, and the chosen restoration material was resin
      composite.

PMID- 17530051
TI  - An in vitro evaluation of a prototype Delrin carrier for the Thermafil obturation
      system.
AB  - OBJECTIVE: To produce and test a prototype carrier for the Thermafil obturation
      system. METHOD AND MATERIALS: A prototype carrier was created in a new plastic
      material (Delrin) with a new profile design made up of 15 intersecting cones of
      decreasing diameter and a 0.06 taper. Thirty extracted premolar teeth were root
      filled, 15 with obturators with the prototype carriers and 15 with the
      traditional Thermafil obturators. The samples were made transparent and examined
      with an optical microscope equipped with a millimeter scale in order to observe
      the aspect of gutta-percha stripping from the carrier and evaluate its degree by
      measuring the length of carrier deprived of gutta-percha on the buccal, mesial,
      distal, and lingual root surface. The analysis of variance (ANOVA) test was
      carried out for statistical analysis. RESULTS: The prototype carriers made
      contact with the dentinal walls (mean length of stripping: 5.80 mm for size 25,
      3.42 for 30, and 1.40 for 35) but less than the traditional Thermafil obturators
      (mean length of stripping: 6.68 mm for size 25, 7.98 for 30, and 6.86 for 35).
      The ANOVA test revealed no statistically significant difference between groups
      for P <.01. The prototype carriers contacted the walls in short horizontal band
      shaped areas around the circumference, while the Thermafil obturators had contact
      in long vertical strip-shaped areas. CONCLUSION: The prototype carrier,
      contacting the dentinal walls in short areas all around the circumference, allows
      the centering of the obturator into the root canal.

PMID- 17530052
TI  - Effect of different bleaching techniques on enamel surface microhardness.
AB  - Conservative techniques for treatment of discolored human enamel include in
      office bleaching with heat-activated 35% hydrogen peroxide, Nightguard vital
      bleaching with 10% carbamide peroxide, and enamel microabrasion with 18%
      hydrochloric acid. OBJECTIVES: In this study, these bleaching techniques were
      performed on 30 extracted teeth to evaluate their effects on microhardness of
      enamel surfaces. METHODS: The enamel surface microhardness measurements were
      performed 0, 24, 48, and 72 hours and 1 week after treatment. Paired t tests were
      performed in the statistical analyses. RESULTS: No changes were found on
      specimens treated with carbamide peroxide. There was a significant decrease in
      the surface microhardness of enamel after 0 and 24 hours when the specimens were
      treated with 18% hydrochloric acid (softening 85.7 and rehardening 99.4) or with
      35% hydrogen peroxide (softening 85.7). However, after 72 hours, significant
      rehardening was observed in these groups (P <.001). CONCLUSION: According to the
      results, except Nightguard vital bleaching, all other techniques softened the
      enamel surface.

PMID- 17530053
TI  - Bond strength of adhesives to dentin involving total and self-etch adhesives.
AB  - OBJECTIVE: Currently, the trend in dentin adhesion seems to be shifting from
      moist bonding systems to self-etching systems and from several application steps
      to single steps. However, recent studies have indicated that the performance of
      single-step adhesives was lower than the 2-step self-etch or total etch systems.
      In the present study, microtensile bond strength of a total etch, 2-step self
      etch and single-step self-etch adhesives was comparatively evaluated. METHOD AND
      MATERIALS: The superficial occlusal dentin of 12 noncarious extracted human
      molars was exposed, finished with wet 600-grit silicon carbide paper, and a block
      of resin composite bonded with adhesives according to the manufacturers'
      instructions. The teeth were kept in tap water for 24 hours at 37 degrees C and
      sectioned to produce beams, with adhesive areas of +/- 0.9 mm2 (4 beams per tooth
      were obtained). The specimens were stressed at a crosshead speed of 1 mm per
      minute until the bonds ruptured. RESULTS: The mean bond strengths were calculated
      as MPa and compared by performing analysis of variance and Tukey tests to
      identify significant differences between the materials (P = 0.05). The mean bond
      strength of Clearfil SE Bond was significantly higher than that of OptiBond Solo
      Plus and iBond (P <.05). OptiBond Solo Plus gave significantly higher bond
      strengths than iBond (P <.05). CONCLUSIONS: The self-etching adhesive system
      Clearfil SE Bond (2 step) had higher bond strength than the 1-bottle self-etching
      adhesive iBond (single application) and the 2-step single-bottle system OptiBond
      Solo Plus (total etch). However, the 1-bottle adhesive system OptiBond Solo Plus
      (total etch system) had higher bond strength than the 1-bottle self-etching
      adhesive system iBond.

PMID- 17530054
TI  - Microbial acid production (Clinpro Cario L-Pop) and dental caries in infants and
      children.
AB  - OBJECTIVE: The purpose of this study was to evaluate the diagnostic utility of
      the Clinpro Cario-L-Pop test as it relates to dental caries rates and severity in
      infants and children. METHOD AND MATERIALS: The study population was comprised of
      771 infants and children who were on average 5.2 years of age (range of 1.5 to 8
      years of age). Examiners conducted dental caries clinical examination using
      established criteria. In addition, lesion severity was determined be measuring
      its depth. An indicator swab was applied to the tongue dorsum until completely
      moistened with saliva. The indicator swab was processed according to the
      manufacturer's instructions, and acid production was assessed with the aid of a
      color chart. RESULTS: Twenty-three percent of children were caries free, and 7%
      (n = 50) of participants were categorized as having low production of lactic acid
      (scores 1 to 3), 17% (n = 135) moderate production of lactic acid (scores 4 to
      6), and 76% (n = 586) high production of lactic acid (scores 7 to 9). There was a
      tendency for moderate and high lactic acid formers to exhibit higher surface
      based caries prevalence rates, higher rates for deep dentinal lesions, and
      increased lesion severity. There was a linear increase of white spot surface
      based lesions from low to high lactic acid formers and for initial dentinal
      lesions. Clinpro Cario-L-Pop test results, when controlling for age and gender,
      significantly distinguished caries-free participants from those exhibiting any
      form of decay. CONCLUSION: These results suggest that Clinpro Cario-L-Pop test
      was useful in explaining elevated frequency and severity of dental caries in
      spite of the high levels of decay and of microbial acid production observed in
      this population.

PMID- 17530055
TI  - Creation of a nonsurgical papilla in orthodontic treatment with severe
      periodontal disease: a case report.
AB  - This case report describes the nonsurgical creation of an interdental papilla in
      orthodontic therapy of a patient with severe periodontal disease. A large
      diastema between the maxillary incisors was closed completely, and the lost
      interdental papilla was re-created by orthodontic therapy after nonsurgical
      periodontal therapy. Radiographs showed improvement of the bone defect.
      Periodontal/orthodontic soft tissue manipulation is a nonsurgical technique that
      can lead to reformation of the interdental papilla, provided that periodontal
      health is maintained.

PMID- 17530056
TI  - [Evaluation of ischemic injury of the spinal cord following endoprosthesis
      implantation in the thoraco-abdominal aorta on a rat model].
AB  - INTRODUCTION: Spinal cord ischemia is one of the most dreaded complication which
      may occur after conventional surgery of the thoraco-abdominal aorta, as well as
      following endoprostheses implantation. A better understanding of its pathogeny
      and physiopathology may lead to the introduction of means or measures for its
      prevention. The widespread utilization of the endovascular management of thoraco
      abdominal aortic pathology stimulated the search for new alternatives to overcome
      the problem. MATERIAL AND METHODS: An experimental study was conducted, using
      Wistar-Lewis rats. Thirty-six animals were employed to assess the spinal cord
      consequences following the implantation of PTFE endoprosthesis in the thoraco
      abdominal aorta. The endoprostheses were introduced through a distal aortotomy
      and advanced until the limits of the subclavian artery, down to the celiac axis.
      A similar group of animals underwent the conventional surgical management. To
      evaluate the neurologic repercussions, a sensor was placed in the spinal cord
      aimed at the registry of the bioelectric potentials, every two hours, until a
      limit of eight hours, in subgroups of six animals. Finally, the spinal cord was
      removed for histological examination. RESULTS AND DISCUSSION: The collected data
      revealed that significant ischemic alterations occurred eight hours after the
      implantation of the endoprostheses and that 48 hours later some signs of recovery
      could be observed, probably by means of collateral blood flow arising from the
      spinal cord itself or from branches of the thoraco-abdominal vasculature.
      However, it must be stressed that these results were obtained in healthy animals,
      with normal arteries, and that the resistance of the nervous tissues to the
      ischemia is certainly lower than in individuals with previous arterial pathology.

PMID- 17530057
TI  - [The forgotten world of venous endothelium--a plea for research].

PMID- 17530058
TI  - [More and better].

PMID- 17530059
TI  - [National Registry of Adults Cardiac Surgery: our patients profile].
AB  - A task force commission was created with the support of the Portuguese Society
      for Cardiothoracic and Vascular Surgery with the aim of organizing a National
      Adult Cardiac Surgery Registry, collecting clinical data and types of cardiac
      surgical procedures performed in Portugal. Selected variables include risk
      factors, cardiac status, preoperative hemodynamics, surgical procedure, hospital
      stay and mortality. The aim of the project is still far from the expected.
      However, patients' preoperative risk is clearly shown, based on demographic data
      and risk factors.

PMID- 17530060
TI  - [Global experience and results of heart transplantation].
AB  - OBJECTIVES: This article summarizes the general experience and results achieved
      by heart transplantation during 19 years of activity. MATERIALS AND METHODS:
      Between 1987 and 2005, 439 heart transplantations and 24 cardiopulmonary
      transplantations were performed by the Cardiovascular Surgery Department of
      Hospital Universitario La Fe, Valencia, Spain. Indication variation over time,
      donor/receptor profiles, urgent vs. programmed transplantations and short/long
      term results over different periods of time were subject to analysis, while
      correlating the results with changes of surgical technique, myocardial protection
      and immunosuppression protocols. RESULTS: For the last 5 years, the number of
      heart transplantations remained stable at 30 cases per year. The most frequent
      etiology was ischaemic cardiopathy (41%); 25% of the emergency heart
      transplantations were carried out in patients with inotropic support, mechanical
      ventilation and/or intraaortic balloon pump contrapulsation. The early mortality
      rate was 8%, and 4,7% considering only the last period; the most frequent cause
      of death during the first postoperative month was acute graft failure, followed
      by infection. After the first year, graft vascular disease was the leading cause
      of mortality. Emergency transplantation and re-transplantation had a
      significantly higher mortality. CONCLUSIONS: Cardiac transplantation is the best
      treatment for terminal miocardiopathies. The early mortality rate was low. At
      present time, the number of heart transplantations became stable due to a low
      number of donors. In the future, better prevention and treatment of graft
      vascular disease shall be achieved in order to increase long-term survival. The
      comparative analysis of survival shows similar results to others published in the
      world scientific literature, including a continuing trend towards improving
      survival over the last years.

PMID- 17530061
TI  - [Inflammatory pseudotumor of the lung. Case report].
AB  - Inflammatory pseudotumor of the lung is a rare entity, of unknown etiology and
      variable clinical evolution. The histological variety of this entity makes the
      diagnosis difficult, which is generally obtained after surgical removal of the
      lesion. The authors report the clinical case of a 32 years old woman presenting
      with hemoptysis and radiologic appearance of aspergilloma. The lesion was
      surgically removed and the diagnosis of inflammatory pseudotumor of the lung was
      confirmed by pathologic and immunohistochemical analysis.

PMID- 17530062
TI  - [Traumatic rupture of the thoracic aorta: long-term results].
AB  - INTRODUCTION: Traumatic rupture of the thoracic aorta (TRTA) is a life
      threatening condition usually caused by deceleration mechanism following vehicle
      accidents. OBJECTIVE: To report our experience with the conventional surgical
      treatment of TRTA and its long-term results. PATIENTS AND METHODS: We reviewed
      five patients assisted in our Service between 1990 to 2006. Four of them
      underwent the conventional surgical treatment and the remaining patient was
      submitted to an endovascular approach, by other surgeon due to high-risk
      comorbidities. We evaluated the perioperative morbity and mortality, as well as
      the long-term results. RESULTS: All the four cases were male, aged between 21 and
      54 years old. Three patients were victims of vehicle accidents and one patient
      reported a fall from a stair. Two patients were operated on in the acute fase of
      TRTA (5 and 17 days) and another two patients had delayed treatment (4 months and
      10 years later). No death or permanent neurologic deficits were noticed. One
      patient had temporary parestesias of lower limbs with complete recover in three
      weeks. The follow-up duration was one to 16 years; no deaths, reinterventions or
      other complications were observed. CONCLUSION: Although the small number of
      patients of the present series, we would like to stress the quality of long-term
      results of the surgical management of TRTA, undertaken in young patients, with a
      long-life expectancy.

PMID- 17530063
TI  - [Surgical management of a chronic post traumatic dissection of the abdominal
      aorta].
AB  - The clinical case of a 34 years old male is reported, who was referred to our
      clinic complaining of disabling claudication of the lower extremities. No risk
      factors for atherosclerotic disease could be identified. Six years previously he
      sustained a severe automobile crush injury, resulting in cranio-encephalic and
      abdominal trauma, and fractures of the left knee and both legs. Appropriate
      medical and surgical care were delivered and he recovered completely, with no
      restrictions. Six months before the observation, he started to complain of
      intermittent claudication of both legs. An angio-CT evaluation disclosed the
      diagnosis of a chronic dissection of the abdominal aorta of post traumatic
      etiology, causing significant restriction of blood flow to the lower extremities.
      The patient underwent surgical management consisting of the resection and
      prosthetic replacement of the abdominal aorta. The post operative course was
      uneventful and he became asymptomatic. A control angio-CT study revealed the
      graft working in excellent condition. The main features of this clinical entity
      are analyzed and discussed based on a clinical revision of the bibliography on
      the subject.

PMID- 17530064
TI  - [Thrombotic occlusion of an abdominal aortic aneurysm].
AB  - The clinical condition of a 78 years old male is reported, with a thrombotic
      occlusion of an abdominal aortic aneurysm, expressed by the acute onset of
      intermittent claudication of both legs, two months previously to the observation.
      On physical examination a pulsatile mass was observed in the abdomen, with no
      expansion, with 7 cms of diameter; femoral pulses were absent. CT-scans confirmed
      the clinical diagnosis, revealing the presence of a recent thrombus occluding the
      aortic lumen. The patient underwent the conventional open surgery, consisting in
      the resection of the aneurysm and replacement with a prosthetic graft, from the
      aorta to both common femoral arteries. The post-operative course was uneventful
      and the patient was discharged, asymptomatic, having recovered peripheral pulses
      in both legs. The main aspects of this rare complication of the abdominal aortic
      aneurysm are reviewed and discussed, based on the information of the literature
      on the subject.

PMID- 17530065
TI  - [Epidemiology of chronic wounds treated in Primary Health Care in Portugal].
AB  - This cross-sectional study of a sample of patients with wounds of duration > 2
      weeks, attempts to characterize patients and type of wounds treated in community
      services and assess patient's views with regard to wounds and care received. 144
      health centres were randomly selected so as to be nationally representative.
      RESULTS: 1424 wounds in 1115 patients aged > or = 18 yrs were assessed. Of these,
      57.4% were treated in the clinic and 42.6% at home. There was a predominance of
      female patients (57.7%) and average age was 69.9 (clinic) and 77.1 (home) years.
      Over 80% of patients were retired. Leg ulcers were the main type of wound,
      followed by pressure ulcers. Average wound duration was 7.4 months for pressure
      ulcers and 19.4 months for leg ulcers. Of 574 clinic patients a significant
      number complained of discomfort and pain but over 90% were satisfied with care
      received. DISCUSSION: Patient population was characterized as elderly, low income
      and suffering from chronic underlying disease. Expectations regarding healing are
      low. An education/ intervention project has been started to promote evidence
      based practice.

PMID- 17530066
TI  - [Duplex ultrasound investigation of the veins in chronic venous disease of the
      lower limbs--UIP consensus document part I: basic principles].
AB  - OBJECTIVES: Duplex ultrasound investigation has become the reference standard in
      assessing the morphology and haemodynamics of the lower limb veins. The project
      described in this paper was an initiative of the Union Internationale de
      Phlebologie (UIP). The aim was to obtain a consensus of international experts on
      the methodology to be used for assessment of veins in the lower limbs by
      ultrasound imaging. DESIGN: Consensus conference leading to a consensus document.
      METHODS: The authors invited a group of experts from a wide range of countries to
      participate in this project. Electronic submissions from the experts were made
      available to all participants via the UIP website. The authors prepared a draft
      document for discussion at a UIP Chapter meeting held in San Diego, USA in August
      2005. Following this meeting a revised manuscript was circulated to all
      participants and further comments were received by the authors and included in
      subsequent versions of the manuscript. Eventually all participants agreed to the
      final version of the paper. RESULTS: The experts have made detailed
      recommendations concerning the methods to be used for duplex ultrasound
      examination as well as the interpretation of images and measurements obtained.
      This document suggests a methodology for complete assessment of the superficial
      and perforating veins of the lower limbs, including recommendations on reporting
      results and training of personnel involved in these investigations. CONCLUSIONS:
      The authors and a large group of experts have agreed to a methodology for the
      investigation of the lower limbs venous system by duplex ultrasonography.

PMID- 17530067
TI  - [Ventral aorta and abdominal visceral arterial revascularization in Takayasu's
      disease: angio-CT evaluation 23 years after the operation].

PMID- 17530068
TI  - Alkali-metal bis(aryl)formamidinates: a study of coordinative versatility.
AB  - The development of alkali-metal amidinate reagents, in particular formamidinates,
      has proceeded hand-in-hand with fundamental advances in transition-metal bonding,
      e.g. metal-metal bonding, and the progressive departure from cyclopentadienyl
      support ligands in early transition-metal catalysis. This highly personalised
      account highlights the coordinative versatility of one alkali-metal amidinate
      subclass; the bis(aryl)formamidinates. These compounds have proven invaluable
      during transition-metal studies but were considered unworthy of investigation in
      their own right prior to our work.

PMID- 17530069
TI  - MMX polymer chains on surfaces.
AB  - Fibres of [Ru(2)Br(micro-O(2)CEt)4]n polymer have been isolated on different
      surfaces under specific conditions, and morphologically characterised by AFM and
      STM, showing an unexpected helical internal structure.

PMID- 17530070
TI  - Reversible solid-state reaction between 18-Crown[6] and M[H2PO4](M = K, Rb, Cs)
      and an investigation of the decomplexation process.
AB  - On heating the hydrated complexes 18-Crown[6].M[H(2)PO(4)].xH(2)O (x= 2 for M =
      K, Rb; x= 1.5 for M = Cs), quantitatively prepared by mechanical mixing of
      crystalline 18-Crown[6] and M[H(2)PO(4)], to ca. 60 degrees C, water loss takes
      place, accompanied by the extrusion of the crown ether from the crystalline
      complex and followed by reconstruction of the inorganic phase M[H(2)PO(4)](M = K,
      Rb, Cs); the resulting solid mixture reverts to 18-Crown[6].M[H(2)PO(4)].xH(2)O
      (x= 2 for M = K, Rb; x= 1.5 for M = Cs) upon grinding in air.

PMID- 17530071
TI  - Formation and evaluation of electrochemically-active ultra-thin palladium-Nafion
      nanocomposite films.
AB  - A simple method for producing electrochemically-active palladium nanoparticles
      within ultra-thin Nafion films is described.

PMID- 17530072
TI  - Solvent inclusion in form II carbamazepine.
AB  - We report on experimental and theoretical evidence for solvent inclusion in form
      II carbamazepine (R3) and discuss the implications for the formation and
      stability of this form.

PMID- 17530073
TI  - Coding a coordination-driven self-assembly via a hydrogen bond-directed solid
      state synthesis: an unexpected chiral tetrahedral capsule.
AB  - An achiral ligand, synthesized in the solid state via a coded hydrogen bond
      directed organic synthesis, self-assembles with Cu(II) ions to form a chiral
      tetrahedral capsule that hosts an anion as a guest.

PMID- 17530074
TI  - A cavitand stabilizes the Meisenheimer complex of SNAr reactions.
AB  - A deep cavitand binds amine nucleophiles and accelerates their subsequent S(N)Ar
      reactions by solvating the intermediate Meisenheimer complex.

PMID- 17530075
TI  - Photochromism of 7-(N,N-diethylamino)-4'-hydroxyflavylium in a water-ionic liquid
      biphasic system.
AB  - Photochromism of trans-4-(N,N-diethylamino)-2,4'-dihydroxychalcone, with
      formation of the photoproduct 7-(N,N-diethylamino)-4'-hydroxyflavylium, is
      promoted in the ionic liquid phase of a water/[bmim][PF6] biphasic system.

PMID- 17530076
TI  - Photoreactive immobilization of 11-(2,4-dinitro-5-fluorobenzene)undecenamide on a
      hydrogenated silicon (100) surface for protein immobilizations.
AB  - Several nucleophiles such as proteins or poly(ethyleneimine) could be easily
      conjugated with a 11-(2,4-dinitro-5-fluorobenzene)undecenamide (DFUA) monolayer
      photochemically prepared on a silicon (100) surface.

PMID- 17530077
TI  - Effects of cucurbit[7]uril on enzymatic activity.
AB  - The macrocyclic host cucurbit[7]uril exhibits highly specific inhibitory effects
      on the activity of proteases, which can be analyzed by a host-substrate
      complexation model.

PMID- 17530078
TI  - A Ramberg-Backlund route to the stilbenoid anti-cancer agents combretastatin A-4
      and DMU-212.
AB  - A concise route to combretastatin A-4, a potent inhibitor of tubulin
      polymerisation, using a Ramberg-Backlund reaction to form the key (Z)-stilbene
      unit has been developed; this Ramberg-Backlund approach has also been extended to
      prepare the (E)-stilbene DMU-212, which also possesses interesting growth
      inhibitory properties.

PMID- 17530079
TI  - The asymmetric vinylogous Mannich reaction of dicyanoalkylidenes with alpha-amido
      sulfones under phase-transfer conditions.
AB  - The stereoselective vinylogous Mannich reaction of dicyanoalkylidenes under phase
      transfer catalytic conditions utilizing stable alpha-amido sulfones as imine
      precursors is presented; a rigid pyrrolidinium salt acts as the phase-transfer
      catalyst, giving access to the amino alkylated products in generally good yield
      and up to 95% ee.

PMID- 17530080
TI  - Distinct nanostructures from isomeric molecules of bis(iminopyrrole) benzenes:
      effects of molecular structures on nanostructural morphologies.
AB  - The effects of molecular structures on nanostructural morphologies have been
      studied through the preparation of nanospheres, square nanowires, and nanocubes
      from three isomeric molecules of bis(iminopyrrole)benzene.

PMID- 17530081
TI  - Microreactor utilizing a vertically-aligned carbon nanotube array grown inside
      the channels.
AB  - We have fabricated a microreactor incorporating vertically-aligned carbon
      nanotubes supporting Pt nanoparticles and found that the presence of aligned
      nanotubes significantly enhances the catalytic reaction and extends the catalyst
      lifetime as compared with conventional microreactors using a Pt metal film or Pt
      nanoparticles directly deposited on the channel walls.

PMID- 17530082
TI  - Advancements in natural abundance solid-state 33S MAS NMR: characterization of
      transition-metal M=S bonds in ammonium tetrathiometallates.
AB  - We report the first (33)S chemical shift anisotropy (CSA) data as obtained from a
      combined determination of (33)S CSA and quadrupole coupling parameters utilizing
      the observation of both the (33)S (I = 3/2) central and satellite transitions in
      a natural abundance (33)S MAS NMR study aimed at characterizing the two important
      tetrathiometallates (NH4)(2)MoS(4) and (NH4)(2)WS(4).

PMID- 17530083
TI  - Diastereoselective photocycloaddition using memory effect of molecular chirality
      controlled by crystallization.
AB  - Naphthamides derived from L-proline, which exist as a mixture of several
      diastereomers in solution, converged to single diastereomer by crystallization,
      and the conformational transformation was controlled after the crystals were
      dissolved in the solvent at low temperature, where the frozen conformation was
      retained long enough for subsequent asymmetric reaction.

PMID- 17530084
TI  - Straight-chain alkanes template the assembly of water-soluble nano-capsules.
AB  - Cavitand is sufficiently predisposed to form nano-scale capsules in the presence
      of templating straight-chain hydrocarbons; quaternary complexes are formed when
      two copies of smaller guests are encapsulated, whilst larger guests form ternary
      entities.

PMID- 17530085
TI  - Supermolecule density functional calculations suggest a key role for solvent in
      alkaline hydrolysis of p-nitrophenyl phosphate.
AB  - Supermolecule density functional theory calculations show that solvent is
      responsible for the concerted transition state in alkaline hydrolysis of p
      nitrophenyl phosphate suggested by heavy atom kinetic isotope effects.

PMID- 17530086
TI  - Structural variations in bimetallic sodium-magnesium and sodium-zinc ketimides,
      and a sodium-zinc alkide-alkoxide-amide: connections to ring-stacking, ring
      laddering, and inverse crown concepts.
AB  - The first sodium-magnesium and sodium-zinc ketimido complexes display contrasting
      inverse crown ring and pseudo-cubane structures respectively, while a sodium-zinc
      heterotrianionic alkide-alkoxide-amide adopts a third type of structure with a
      stepped ladder motif.

PMID- 17530087
TI  - Fabrication of silica-coated magnetic nanoparticles with highly photoluminescent
      lanthanide probes.
AB  - Bi-functional nanoparticles (NPs) that consist of silica-coated magnetic cores
      and luminescent lanthanide (Ln) ions anchored on the silica surface via organic
      linker molecules are reported. Compared to individual Ln ions, the hybrid NPs
      show a drastically enhanced photoluminescence due to the efficient ligand-to
      metal energy transfer in the Ln-loaded NPs: the new bi-functional NPs could be
      used in a variety of biological applications involving magnetic separation and
      optical detection.

PMID- 17530088
TI  - Diamidonaphthalene-supported pnictogenium cations: synthesis of an N-heterocyclic
      stibenium cation by a novel protonation route.
AB  - A 1,8-bis(alkylamido)naphthalene framework has been applied to the construction
      of N-heterocyclic arsenium and stibenium cations; a novel synthetic route,
      involving protonation of an ancillary amido ligand, was used to generate the base
      stabilized stibenium cation.

PMID- 17530089
TI  - X-ray structure and DFT study of C1-C60(CF3)12. A high-energy, kinetically-stable
      isomer prepared at 500 degrees C.
AB  - The title compound, prepared from C(60) and CF(3)I at 500 degrees C, exhibits an
      unusual fullerene(X)12 addition pattern that is 40 kJ mol(-1) less stable than
      the previously reported C(60)(CF(3))12 isomer.

PMID- 17530090
TI  - Enhanced reactivity of hydrophobic vitamin B12 towards the dechlorination of DDT
      in ionic liquid.
AB  - The electrolytic reductive dechlorination of 1,1-bis(p-chlorophenyl)-2,2,2
      trichloroethane (DDT) in the ionic liquid (IL) 1-butyl-3-methylimidazolium
      tetrafluoroborate ([bmim][BF(4)]) in the presence of a cobalamin derivative
      afforded 1,1'-(ethylidene)bis(4-chlorobenzene)(DDO) and 1,1'-(ethenylidene)bis(4
      chlorobenzene)(DDNU) with 1,1'-(2-chloroethylidene)bis(4-chlorobenzene)(DDMS);
      the enhanced reactivity, as well as the recyclability of the cobalamin derivative
      catalyst in IL, makes the present system more efficient for the development of
      "green" technologies.

PMID- 17530091
TI  - Facile approach to enhance the Pt utilization and CO-tolerance of Pt/C catalysts
      by physically mixing with transition-metal oxide nanoparticles.
AB  - A very simple and promising method to design the anode catalyst architecture for
      direct alcohol fuel cells by physically mixing Pt/C catalyst with transition
      metal oxide nanoparticles is presented and electrochemical measurements confirm
      that this unique catalyst structure has excellent activity toward alcohol and CO
      electro-oxidation.

PMID- 17530092
TI  - An entry route into non-aqueous plutonyl coordination chemistry.
AB  - The Pu(VI) molecular complex, [PuO(2)Cl(2)(thf)(2)]2, is prepared by addition of
      a HCl/Et(2)O solution to a suspension of PuO(2)CO(3) in thf, yielding the first
      example of a precursor suitable for investigation of the non-aqueous chemistry of
      the plutonyl dioxo cation under inert atmospheric conditions.

PMID- 17530093
TI  - Is hepatocellular carcinoma preventable?

PMID- 17530094
TI  - Local ablation therapy for hepatocellular carcinoma. From ethanol injection to
      radiofrequency ablation.
AB  - This article reviews the current status of local ablation therapy for
      hepatocellular carcinoma HCC. In the treatment of HCC, non-surgical treatments
      play important roles since only 20-30% of patients are candidates for surgery.
      Still worse, even after curative surgical resection, 80% of patients develop
      recurrence within 5 years. Among non-surgical treatments, image-guided local
      ablation therapies have been widely used for cases of small-number and small-size
      lesions, because they are potentially curative, minimally invasive, and easily
      repeatable. Although percutaneous ethanol injection has long been a standard
      therapy, there has been a drastic shift from ethanol injection to radiofrequency
      ablation in recent years. Randomized controlled trials proved that radiofrequency
      ablation is superior to ethanol injection in the treatment of HCC from the
      viewpoint of not only treatment response but also long-term survival.
      Radiofrequency ablation will play more important roles in the treatment of HCC.

PMID- 17530095
TI  - Innervation pattern of the pronator teres muscle.
AB  - OBJECTIVE: To determine the innervation patterns of the pronator teres muscle
      (PTM), which is used as a donor in muscle transfer. METHODS: This study was
      conducted from 2001-2006 at the Anatomy Department of the Medical Faculty of
      Cerrahpasa, University of Istanbul. There were 34 upper extremities of 17 fixed
      adult cadavers dissected. RESULTS: The classical pattern of innervation by the
      superior and inferior branches of the median nerve was observed in 19 of the
      cases (55.9%). In 4 forearms (11.8%) one branch in 10 (29.4%), 3 branches (2
      humeral, 1 ulnar) and in one (2.9%), 4 branches (3 humeral, 1 ulnar) were found
      to be innervating the muscles. CONCLUSION: In all cases, the humeral and ulnar
      head of the PTM was innervated separately. These variations are of great
      importance during transfer of PTM.

PMID- 17530096
TI  - Role of lipase in glucose and lipid metabolisms.
AB  - OBJECTIVE: To investigate the role of lipase in glucose and lipid metabolisms.
      METHODS: A prospective study involving 52 diabetics (28 males and 24 females,
      mean age 47.67 +/- 15.63 years) and 118 normoglycemic controls (39 males and 79
      females, mean age 38.91 +/- 16.61 years) was conducted, between February 1st and
      August 31st, 2006, at King Abdullah Hospital, Bisha, Saudi Arabia. After 10-12
      hours fasting, blood was taken from subjects and controls for the determination
      of glucose, total cholesterol, triglyceride, low-density lipoprotein (LDL)
      cholesterol, high density lipoprotein (HDL)-cholesterol, and lipase. The results
      were analyzed by student's t-test and Pearson correlation coefficient. RESULTS:
      The levels of glucose, total cholesterol, triglyceride, LDL-cholesterol, and
      lipase were significantly more in the diabetics (p<0.05). However, HDL
      cholesterol was less in the diabetics than the controls, although the difference
      was not significant (p>0.05). There were significant positive correlations
      between glucose, total cholesterol, triglyceride, and lipase; while, significant
      negative correlations were obtained between LDL-cholesterol, HDL-cholesterol, and
      lipase. CONCLUSION: The higher concentrations of glucose, total cholesterol,
      triglyceride, and LDL-cholesterol, as well as the lower HDL-cholesterol in the
      diabetics were typical and not unexpected, as diabetes mellitus is associated
      with disturbance of lipid metabolism. The lipase activity was elevated at
      increased concentrations of glucose and lipids. Hence, it was concluded that the
      pancreatic lipase was possibly involved in the metabolisms of both glucose and
      lipids. Lipolysis has been suggested as the link between the 2 processes.

PMID- 17530097
TI  - Heat shock protein 60 antibody. A new marker for subsequent atrial fibrillation
      development.
AB  - OBJECTIVE: To examined the pre- and post- operative anti-HSP60 antibodies of
      serum from patients in preoperative sinus rhythm. METHODS: We prospectively
      studied 45 consecutive patients admitted for elective CABG from 2004 to 2005. We
      randomly selected 10 patients developing AF (study sample [Group A]) and 10
      postoperative patients without AF (control [Group B]. The study took place at the
      Department of Cardiovascular Surgery, Hacettepe University, Ankara, Turkey.
      RESULTS: Anti-HSP60 IgG value was 27.76 +/- 12.69 absorbance units (AU) in Group
      A preoperatively and decreased to 13.73 +/- 5.51 AU postoperatively.
      Controversially, preoperative value of anti-HSP60 IgG was 9.94 +/- 2.92 AU and
      decreased to 6.72 +/- 1.89 AU, postoperatively in Group B. Statistical analysis
      showed significant difference regarding preoperative anti-HSP60 IgG levels in
      Group A compared to Group B, which might be interpreted as an association between
      postoperative AF and preoperative levels of anti-HSP60 IgG. CONCLUSION: We
      provide the first evidence demonstrating the association of pre- and post-
      operative circulating anti-HSP60 antibodies with postoperative AF. These results
      suggest that serum HSP60 antibody levels may be a marker for subsequent
      development of AF.

PMID- 17530098
TI  - Coronary artery bypass grafting on beating heart. Does it provide superior
      myocardial preservation than conventional technique?
AB  - OBJECTIVE: To compare myocardial injury caused by 3 commonly used methods for
      coronary artery bypass grafting (CABG). METHODS: A prospective randomized study
      conducted at King Khalid University Hospital, Riyadh, Kingdom of Saudi Arabia.
      The study started in February 2003 and concluded in April 2004 after including 45
      patients (15 patients in each of 3 sub-groups) who fulfilled the inclusion and
      exclusion criteria. The subgroups included coronary artery bypass surgery
      performed by: a) conventional technique, b) off-pump technique, and c) on-pump
      beating-heart techniques. All patients had similar operative risk profiles. Their
      ages were 70 years or less with an ejection fraction of 30-50%. The creatine
      kinase, myocardial band (CKMB) levels were determined 2 hours after arrival from
      the operating room then, at 4 hours, 6 hours, and 12 hours. The comparison of
      creatine phosphokinase and CKMB levels was carried out using analysis of variance
      with repeated measures. The p-values were used to evaluate the significance of
      differences. RESULTS: The pre-operative characteristics including age, gender,
      ethnic origin, diabetes mellitus, hypertension, and left ventricular function,
      were similar in the 3 groups. All groups had a median number of 3 bypass grafts.
      The stay in the intensive care unit and the duration of inotropes were shortest
      in the off-pump group, but the difference was not significant. There was a peak
      of CKMB levels at 6 hours in all groups. The trend of CKMB level showed
      significantly higher values in the conventional CABG group as compared with the
      other 2 groups. CONCLUSION: This study indicates that the off-pump technique
      provides better myocardial preservation than other methods.

PMID- 17530099
TI  - Effects of standard and low dose 17beta-estradiol plus norethisterone acetate on
      body composition and leptin in postmenopausal women at risk of body mass index
      and waist girth related cardiovascular and metabolic disease.
AB  - OBJECTIVE: To compare the effects of standard and low dose of 17beta
      estradiol/norethisterone acetate (E2/NETA) on body composition and leptin in
      postmenopausal women at risk of body mass index (BMI) -and waist girth (WG)
      related cardiovascular and metabolic disease. METHODS: Ninety postmenopausal
      women aged 45-55 years with BMI >or= 25 kg/m2 participated in this 6-month
      prospective, randomized, single-blinded and controlled study, conducted between
      September 2004 and April 2006 at Adnan Menderes University Hospital. According to
      their WG, the subjects were divided into 2 risk groups: WG <88 cm (Group
      increased risk [IR], n=48) or WG >or= 88 cm (Group high risk [HR], n=42). The
      subjects in each group were equally assigned to receive standard or low dose of
      E2/NETA (2 mg E2/1 mg NETA, or 1 mg E2/0.5 mg NETA). Accordingly, the 2 groups
      were divided into 4 subgroups. Serum leptin levels (SLLs), body weight/height,
      waist/hip girth, BMI and waist-to-hip ratio were evaluated before and after
      therapy. RESULTS: In the Group IR, WG decreased significantly only in low dose
      subgroup. In the Group HR, both standard and low dose subgroups had a significant
      reduction in WG. Those who had WG >or= 88 cm showed more reduction than those who
      had WG <88 cm in response to both doses of E2/NETA, insignificantly. Basal SLLs
      had a significant correlation with body weight, BMI and WG. CONCLUSION: Oral
      standard and low dose E2/NETA reduce WG and attenuate the BMI- and waist girth-
      related risk of cardiovascular and metabolic diseases in postmenopausal women.

PMID- 17530100
TI  - Comparison of arterial and venous blood gases analysis in patients with
      exacerbation of chronic obstructive pulmonary disease.
AB  - OBJECTIVE: To investigate whether venous blood gases (VBG) test can be replace by
      an arterial blood gases (ABG) in exacerbation of chronic obstructive pulmonary
      disease (COPD). METHODS: From October 2005 to March 2006, at the Emergency Room
      of Kashan Beheshti Hospital, the data of 107 patients with exacerbation of COPD
      were assessed. Arterial blood gases and VBG samples were obtained simultaneously,
      and indexes of pH, carbon dioxide partial pressure (PCO2), bicarbonate (HCO3),
      oxygen partial pressure (PO2) and Oxygen (O2) saturation level were analyzed.
      RESULTS: The mean +/- SD of indexes in ABG and VBG samples were as follows: pH =
      7.37 +/- 0.47 versus 7.34 +/- 0.047; PCO2 = 53.88 +/- 7.63 mm Hg versus 59.55 +/-
      8.96 mm Hg, HCO3= 30.66 +/- 4.49 mEq/L versus 31.94 +/- 4.39 mEq/L; PO2 = 55.37
      +/- 11.19 mm Hg versus 43.08 +/- 10.54 mm Hg. The average difference between
      indexes in ABG and VBG samples were as follows: pH = 0.0241 +/- 0.004, p<0.001, r
      = 0.864; PCO2 = 5.673 +/- 1.126 mm Hg, p<0.001, r = 0.761; HCO3 = 1.279 +/- 0.604
      mEq/L, p<0.001, r = 0.749; and PO2 = 12.294 +/- 2.115 mm Hg, p<0.001, r = 0.702.
      CONCLUSION: Venous blood gases, especially pH and PCO2 levels have relatively
      good correlation with ABG values. In view of the fact that, this correlation is
      not close, VBG cannot be substitute for ABG in exacerbation of COPD.

PMID- 17530101
TI  - A new device to produce a standardized experimental fracture in the rat tibia.
AB  - OBJECTIVE: To develop and introduce a new device to produce a standardized closed
      experimental fracture in the rat tibia. METHODS: This study took place in the
      Research Laboratory, Medical Faculty, Dokuz Eylul University, in the year 2003.
      We include 20 healthy male white Wistar rats. After pinning both tibia of the rat
      intramedullary with the needle of a sterile injector without any incision, we
      tried to produce a fracture with the pendulum of the device, which was dropped in
      different angles in 9 rats. The tibial diaphysis of 14 rats in the main study
      were fractured at 60 degrees. After the fractures were confirmed radiologically,
      4 tibia underwent pathological analysis to determine the degree of soft tissue
      damage and 24 tibia were examined in terms of histological fracture healing.
      RESULTS: Radiologically, this technique resulted in a transverse or short oblique
      bicortical fracture in the middle of the tibial diaphysis. The healing process
      was well adjusted with the classification of Allen. No noticeable soft tissue
      damage in the fracture region was demonstrated. CONCLUSION: This method of
      producing an easy and reproducible fracture in a standard fashion without
      displacement and minimal soft tissue trauma in laboratory animals with this
      simple apparatus make it a useful technique for bone healing studies.

PMID- 17530102
TI  - Reconstruction of diabetic foot ulcers by lateral supramalleolar flap.
AB  - OBJECTIVE: To report a series of 8 diabetic patients in whom the reconstruction
      of large-sized defect of the foot was performed using lateral supramalleolar
      flap. METHODS: Coverage of the soft tissue defect was carried out by a lateral
      supramalleolar flap in 8 patients who had large-sized, non-healing ulcers at the
      Celal Bayar University, Department of Orthopedics and Traumatology, Manisa,
      Turkey, between 1998-2003. The mean age was 54 years. Preoperatively Doppler
      flowmeter evaluation was performed, and the ischemic index was calculated in all
      patients. RESULTS: The flaps survived except for one patient who had a large
      defect on the heel with low ischemic index. The average healing time of the ulcer
      region and recovery of regular walking status was 34 days. The average healing
      period of the donor site was 35 days. After the average follow-up period of 40
      months, neither infection nor a recurrence of the ulcer was encountered. The
      major problem of the donor area was skin graft breakdown and its non-aesthetic
      appearance due to hypertrophic granulation tissue. CONCLUSION: The lateral
      supramalleolar flap is a reliable option for the reconstruction of large-sized
      diabetic ulcers involving the dorsal aspect of the foot. This can also be used in
      conjunction with local muscle flaps, such as abductor hallucis for covering deep
      and large heel defects when the sural neurocutaneous flap is contraindicated.

PMID- 17530103
TI  - Comparison of blood lead levels of mothers and cord blood in intrauterine growth
      retarded neonates and normal term neonates.
AB  - OBJECTIVE: To compare the blood lead levels of mothers and cord blood in
      intrauterine growth retarded (IUGR) neonates and normal term neonates. METHODS:
      From April to December 2005, we carried out a cross-sectional, prospective study
      in Isfahan University of Medical Sciences, Isfahan, Iran. Blood lead levels were
      measured in the umbilical cord and maternal venous blood samples in 32 mother
      infant pairs with IUGR full term neonates, and 34 mother-infant pairs with normal
      full term neonates. Blood-lead levels were analyzed by atomic absorption
      spectrometry. RESULTS: The mean lead concentration in neonates of IUGR and normal
      groups was not significantly different (107.47 +/- 16.75 versus 113.08 +/- 19.08
      micrometer/L, p=0.2). The mean lead concentration in mothers of IUGR group was
      lower than normal groups, but this difference was not significant (124.56 +/-
      19.71 versus 135.26 +/- 26.91 micrometer/L, p=0.07). Maternal lead levels were
      strongly related with cord blood in both IUGR and normal groups (r=0.8,
      p<0.0001). Maternal and cord blood lead levels was not correlated with birth
      weight of newborns in either group. Overall, 65.6% of IUGR neonates and 76.4% of
      normal neonates was above the critical level defined for lead poisoning as >100
      micrometer/L by the centers for disease control; however, this was not
      statistically different between the groups. CONCLUSION: Our results indicate that
      the mean lead level was not higher in IUGR neonates, and the whole blood lead was
      not related to the birth weight. In addition, maternal and cord blood lead levels
      were strongly correlated, and there were remarkable lead burdens on both the
      mothers and their neonates in this industrial area.

PMID- 17530104
TI  - A national study of gynecological morbidities in Oman. Effect of women's
      autonomy.
AB  - OBJECTIVE: To determine the level of gynecological morbidities and other related
      morbidities; and to examine the effect of women empowerment on the reproductive
      tract infections among currently married Omani women. METHODS: This study is a
      part of the National Health Survey in the Sultanate of Oman, conducted between
      January and March 2000. The total number of households selected was 1968 with a
      total of 2037 ever-married women aged 15-49 years, of them 1662 were eligible to
      complete the gynecological morbidity symptoms questionnaire and to be clinically
      examined for gynecological morbidities. RESULTS: Despite the free facilities
      provided, one in every 4 women had reproductive tract infection and nearly half
      of the women suffer from at least one kind of gynecological disease. The
      prevalence of any sexually transmitted diseases was 4%, approximately 10% had
      combined genital prolapsed and 27% had cervical ectopy. Older women, education,
      work status, urban residence, heads of households, high economic status, and took
      their own decision about going to hospital, are significantly more empowered.
      CONCLUSION: Gynecological morbidity is highly prevalent among ever-married women.
      The contribution of the sexually transmitted diseases to the high prevalence of
      reproductive tract infection appears to be modest. Genital prolapse was one of
      the risk factors for reproductive tract infection, education as a proxy for women
      empowerment was a poor predictor for the occurrence of the diseases.

PMID- 17530105
TI  - Relationship of body weight and volume of liver. A morphometrical and
      stereological study.
AB  - OBJECTIVE: To examine the relationship between high-fat diet induced obesity and
      hepatomegaly, and to investigate whether obesity, or hepatomegaly, or both are
      related to gender. METHODS: This study was performed in 2003 at Ataturk
      University, Erzurum Turkey. Ten adult Sprague Dawley rats (5 male, 5 female) were
      fed with a diet that constituted highly of fat (30%) for duration of 3 months.
      Ten control animals (5 male, 5 female) were maintained with standard chow. At the
      end of the experiment, rats were sacrificed with Sevorane. The body mass index
      (BMI) of all animals was calculated. Finally, the removed livers were
      histologically processed and the liver volume was estimated with unbiased
      Cavalieri method. RESULTS: The BMI was 4.8 +/- 0.3 kg/m2 in males; 4.2 +/- 0.25
      kg/m2 in females (control group), and 5.92 +/- 0.5 kg/m2 in males and 5.425 +/-
      0.40 kg/m2 in females (treatment group). The BMI of the 2 groups was
      significantly different (between both males and females, p<0.01; male to male,
      p=0.035; female to female, p=0.001). Moreover, weight values correlated with
      liver volume, especially in the treated females (r=1.000; p<0.01). CONCLUSION:
      Thus, the results of the present study suggest that gender is a contributing
      factor for overweight and we found that hepatomegaly in women is more than men.

PMID- 17530106
TI  - Helicobacter pylori prevalence among medical students in a high endemic area.
AB  - OBJECTIVE: To evaluate the prevalence of Helicobacter pylori (H. pylori) among
      Saudi medical students. METHODS: Volunteer medical students were randomly
      selected in the College of Medicine, King Saud University, Riyadh, Saudi Arabia
      from January 2005 to May 2005. A urea breath test (UBT) was performed for each
      medical student. Important demographic data was recorded. Each student had to
      answer a questionnaire on upper gastrointestinal (UGI) symptoms before the UBT.
      RESULTS: A total of 120 students were recruited (73 males [61%] and 47 females
      [39%]) with a mean age of 22.2 years (age varied from 18 to 28 years). The
      prevalence of H. pylori was surprisingly low at 35%, compared to a previously
      reported high prevalence among the Saudi population (80%). Thirty-one percent of
      medical students reported >or= 1 UGI symptom with no significant differences
      between the positive and negative UBT results. Although there was a trend, there
      was no significant prevalence difference between the preclinical and the clinical
      group of students. CONCLUSION: We found a low prevalence of H. pylori in our
      young university medical student's population. The low prevalence of H. pylori in
      this young population may have important clinical and economic implications.

PMID- 17530107
TI  - Comparison of arbitrarily primed-polymerase chain reaction and plasmid profiles
      typing of Pseudomonas aeruginosa strains from burn patients and hospital
      environment.
AB  - OBJECTIVE: To identify the strengths and weakness of arbitrary primed-polymerase
      chain reaction (AP-PCR) and plasmid profiles for typing of Pseudomonas aeruginosa
      (P. aeruginosa) and tracking of source of infections. METHODS: Seventy-four
      strains of P. aeruginosa were isolated from burn patients and hospital
      environment between January to April 2003 in Ghotbadden Burn Hospital, Shiraz,
      Iran. The strains were classified by photo Capt Mw program, similarity and
      clustering of strains were assessed using NTSYS-PC version 2.02K software.
      RESULTS: Based on 50% and 64.7% and 67.5% similarity on the plotted dendrogram,
      38 plasmid profiles were classified into: 2, 3 and 5 clusters, respectively.
      Photo Capt Mw program categorized AP-PCR products to 47 different types of 6 to
      12 bands between 0.376 to 3.7 kb. Based on dendrogram pattern 3 levels (62 %, 81%
      and 84.6%) of similarity were selected. Using these criteria 2, 5 and 11 clusters
      were obtained, respectively. CONCLUSION: As compared with plasmid profiles, AP
      PCR analysis protocol is rapid, reproducible and differentiated the isolates with
      higher discrimination power. These results suggest that during admission of
      patients in burn center a limited number of common strains cross-contaminate burn
      victims. However, transmissions of infection from hospital environment to
      patients also occur in the minority of the victims. To control cross
      contamination of the patient wounds with antibiotics resistant isolates, strong
      disinfection of patients' bathroom after scrubbing of each patient wounds is
      mandatory.

PMID- 17530108
TI  - Bupivacaine with meperidine versus bupivacaine with fentanyl for continuous
      epidural labor analgesia.
AB  - OBJECTIVE: To compare the efficacy of bupivacaine-meperidine and bupivacaine
      fentanyl mixtures when continuously infused epidurally to relief the labor pain.
      METHODS: We performed this prospective double-blinded study at Jordan University
      Hospital, Amman, Jordan between October 2005 and April 2006. Sixty-seven American
      Society of Anesthesia physical status I parturients were randomly divided into 2
      groups, Group M (n=34) received a continuous infusion of 1 mg/ml of bupivacaine
      mixed with 1 mg/ml meperidine, and Group F (n=33) received a continuous infusion
      of 1 mg/ml bupivacaine mixed with 2 micrometer/ml fentanyl. Efficacy of
      analgesia, degree of motor block, hemodynamic variability, incidence of nausea
      and vomiting, pruritus, sedation, and the neonatal outcome were all compared
      between the 2 groups. A p value <0.05 was considered to be significant. RESULTS:
      Highly effective analgesia was achieved in both groups with a similar incidence
      of motor block, sedation, pruritus, and neonatal outcome. The only significant
      difference was in the incidence of nausea and vomiting. Group M had 8 parturients
      with nausea, compared with only 2 parturients in Group F (p=0.003). CONCLUSION:
      Bupivacaine-meperidine in a continuous epidural infusion is as efficient as
      bupivacaine-fentanyl for pain relief during labor, but associated with a higher
      incidence of nausea and vomiting.

PMID- 17530109
TI  - Effect of salt intake on blood pressure in diabetic hypertensive patients in
      Saudi Arabia.
AB  - OBJECTIVE: To understand the impact of salt intake on blood pressure and to
      assess the application of international management guidelines in Saudi diabetic
      hypertensive patients. METHODS: We recruited 112 consecutive diabetic
      hypertensive patients visiting the diabetic and nephrology clinic at the King
      Khalid University Hospital between July 2005 and January 2006. Participants
      received complete medical assessment and their 24 hours urine sodium was
      measured. Patients on diuretics were excluded from the study. RESULTS: A
      significant correlation between 24 hours urine sodium and diastolic blood
      pressure concentration was observed (r = 0.25, p=0.04) but not with systolic
      blood pressure (r =0.06, p=0.6) or 24 hours urine protein (r =0.06, p=0.63).
      Approximately 15% of the patients had an glycosylated hemoglobin (A1C) of between
      7-8% while 41.2% had an A1C of >8 (suboptimal group for glycemic control). Low
      density lipoprotein (LDL) cholesterol in only 37.5% of the patients was within
      the desired goal (<2.4 mmol/l). Whereas only 24.8% of the patients achieved the
      goal of systolic and diastolic BP of <130/80 mm Hg. CONCLUSION: Modest salt
      restriction has possible adjuvant effect to pharmacologic treatment to enhance
      blood pressure control. However, a majority of the Saudi diabetic patients with
      hypertension and hyperlipidemia are inadequately treated.

PMID- 17530110
TI  - Tracheobronchial straight metallic pin aspiration in young Jordanian females.
AB  - OBJECTIVE: To define the clinical spectrum of tracheobronchial straight metallic
      pin aspiration in adults, assess predisposing conditions, evaluate the efficacy
      of bronchoscopy, and determine the outcome and complications at the largest 2
      hospitals in Jordan. METHODS: Retrospective analysis of 60 consecutive clinical
      cases from 2 referral-based medical centers (32 patients at King Hussein Medical
      Center [KHMC] and 28 patients at Al-Basheer Hospital). Medical records of adult
      patients (>13 years of age) who presented with history of straight metallic pin
      aspiration over 6-year period (July 2000 and July 2006) were analyzed. Clinico
      radiological features and location of the pins were studied. The flexible
      fiberoptic bronchoscopy (FFB) was used for foreign body (FB) identification and
      removal in all KHMC patients; video assisted rigid bronchoscope under general
      anesthesia was used at Al-Basheer Hospital. RESULTS: All patients were females
      <28 years of age. Fifty-six patients (93%) presented within the first 24 hours
      after aspiration. Medical history was suggestive of FB aspiration in all
      patients. Chest x-rays demonstrated the radio opaque pins in all patients. At
      bronchoscopy, the intermediate bronchus was the most common site of FB lodgment
      (62%). Ninety-two percent of patients were discharged on the same day of the
      procedure. CONCLUSION: Tracheobronchial straight metallic pins are relatively
      frequent FB in Jordanian young females and can occur in a very specific clinical
      setting. Removal of these FBs can usually be accomplished successfully by FFB.

PMID- 17530111
TI  - Sleep medicine service in Saudi Arabia. A quantitative assessment.
AB  - OBJECTIVE: To assess quantitatively sleep medicine services in Saudi Arabia (KSA)
      and identify obstacles that face specialists and hospitals and preclude the
      establishment of this service. METHODS: A self-administered questionnaire was
      mailed to 53 major governmental and private hospitals in KSA on September 2005.
      The response rate was 69.8%. Data were coded and analyzed. RESULTS: The survey
      identified 9 sleep disorders facilities in KSA; 7 were defined as sleep disorders
      centers and 2 as sleep laboratory using the American Academy of Sleep Medicine
      definitions. The per capita polysomnography (PSG) rate was 7.1 PSG/year/100,000
      population, which was much lower than the reported rates in developed countries.
      The occupancy rate of sleep facilities was found to be low (45.7%). The most
      important identified obstacles facing the progress of sleep medicine in KSA were
      lack of trained sleep technicians, shortage of sleep medicine specialists and the
      un-availability of fund or designated space for the facility. CONCLUSION: Sleep
      medicine seems to be underdeveloped in KSA compared to developed countries.
      Organized efforts are needed to overcome the identified obstacles and challenges
      facing the progress of sleep medicine in KSA.

PMID- 17530112
TI  - A randomized trial of smoking cessation. Medication versus motivation.
AB  - OBJECTIVE: A prospective randomized study was undertaken to assess the
      effectiveness and side effect profiles of nicotine patch and bupropion therapies
      for smoking cessation. METHODS: Three hundred and fifty patients were referred to
      our smoking cessation program in the Department of Pulmonary Diseases, Gaziantep
      University between September 2002 and July 2003. Of these, only 131 patients
      fulfilled the trial criteria. We randomized the patients into nicotine patch
      (n=50), bupropion (n=50) and control groups (n=31). Cases were followed up for 24
      weeks. Questionnaires including the Fagerstrom test for nicotine dependence and
      Beck Depression Inventory were carried out at initial evaluation. Declaration of
      quitting and exhaled carbon monoxide level less than 10 ppm was accepted as
      success criteria. RESULTS: Success rates were 26% for nicotine patch group, 26%
      for bupropion and 16% for control group at the end of the 24th week (p=0.56).
      Beck depression inventory scores did not differ significantly between the groups,
      however none of the cases with scores greater than 13 succeeded regardless of the
      group. Mean body weight at baseline and change at 6 months did not differ
      significantly between the groups. Sleep disturbance was significantly more common
      in nicotine patch and bupropion groups than the control group (p=0.008).
      CONCLUSION: The present study reinforces the role of medical doctors and
      importance of close follow up in smoking cessation, and directed counseling is
      quite as effective as pharmacologic therapy and is the sole approach without any
      adverse effects.

PMID- 17530113
TI  - Multiple authorship trends in prestigious journals from 1950 to 2005.
AB  - OBJECTIVE: Editors of many established journals have noticed throughout the years
      an increase in the number of authors per article. I wish to put this theory to
      rest by calculating this linear increase for several prestigious journals.
      METHODS: I chose several prestigious journals and obtained authorship information
      for all articles published throughout the existence of these journals from the
      PubMed website. The data collection was performed on January 22, 2006, and was
      performed for the years from 1/1/1950 to 12/31/2005 for each journal. With the
      use of several self-developed software programs and database queries, I was able
      to calculate the average number of authors per article per year and the percent
      of single-author articles per year for these journals. RESULTS: The result
      confirms the increase in the number of authors per article in a linear fashion
      for all examined journals. The result also shows a decrease in the number of
      single-author articles in a sporadic fashion for all examined journals.
      CONCLUSION: The data collection and calculation method can be used for any
      journal indexed in PubMed. The resulting trends are likely due to the increasing
      complexity of research, the increasing pressure on researchers to publish or
      perish, among others. This paper, however, focuses less on the reasons for this
      trend and more on the computerized methods used to obtain the results.

PMID- 17530114
TI  - Spirituality, religiosity, and dealing with illness in Arabic and German
      patients.
AB  - OBJECTIVE: To investigate the impact of spirituality and religiosity (SpR) in
      Arabic patients with a Muslim background as compared to patients from Western
      Germany. METHODS: A total of 66 Arabic patients with hypertension were recruited
      between November 2005 and June 2006 consecutively at Al-Razi Hospital and Khalil
      Sulaiman Hospital in Jenin (Palestine) and completed the translated SpREUK
      questionnaire (SpREUK is an acronym of the German translation of spiritual and
      religious attitudes in dealing with illness). One hundred and eighty German
      patients were matched according to age, marital status, gender, and chronic
      diseases. RESULTS: Arabic patients with a Muslim background had significantly
      higher scores for all 4 SpREUK scales than German patients, namely, Search for
      meaningful support, Trust in higher source, Positive interpretation of disease,
      and Support in relations of life through SpR. CONCLUSION: For Muslims, the
      spiritual causes of disease are regarded much more as given by Allah, but this
      does neither impair faith as observed in German patients nor the positive
      interpretation of disease. It is of high importance to acknowledge these
      differences due to individuals with different SpR attitudes significantly differ
      in the way they find meaning in disease and hold in their spiritual source.

PMID- 17530115
TI  - Primary pulmonary Hodgkin's lymphoma. A report of 2 cases and review of the
      literature.
AB  - Two cases of primary pulmonary Hodgkin's lymphoma PPHL are presented, a male aged
      21, and a female aged 32 years. Symptoms included non-productive cough, shortness
      of breath, low-grade fever, wheezing, and weight loss. Duration of illness varied
      between 6 weeks in the male patient to 7 months in the female patient. Both
      patients were given an empirical trial of antibiotics and anti-cough measures
      with no response. Radiological studies carried out after failure to respond to
      medical treatment, revealed the presence of pulmonary parenchymal masses in both
      patients. Cytology, bronchoscopic and transbronchial biopsies were not
      diagnostic, which led to opened wedge resections. Finally, the diagnosis of
      primary pulmonary Hodgkin's disease was reached after supportive
      immunohistochemical staining CD30 and CD15 both positive in RS cells. Both
      patients were regarded as stage I extranodal IE after exhaustive measures failed
      to demonstrate involvement of other body sites.

PMID- 17530116
TI  - Pott's puffy tumor. A condition still to be considered.
AB  - In the era of antibiotics, Pott-Puffy Tumor PPT is a rarely recognized entity. An
      11-year-old girl presented with headache, fever for one week, and frontal
      swelling for 3 days. On examination, she was febrile, congested nasal mucosa with
      yellowish nasal discharge and frontal swelling; tender not fluctuating with
      normal eye mobility. Computed tomography CT scan of brain and paranasal sinus
      revealed opacity of maxillary, left ethmoid, frontal sinus opacity and epidural
      collection in the right frontal region with post contrast enhancement. An
      extracranial superficial swelling with fluid collection at the same level of
      epidural collection. The patient underwent bilateral antral washout and left
      frontal sinus trephination, which had resulted into a complete resolving of
      symptoms and an avoidance of further invasive surgical intervention.

PMID- 17530117
TI  - Endometriosis presenting like a psoas abscess.
AB  - Endometriosis is the presence of ectopic endometrial tissue that responds to
      hormonal stimulation. Although endometriosis occurs most often in the pelvis,
      several unusual sites have been reported. We present a case of endometriosis
      mimicking, a psoas abscess. A 39-year-old lady presented with pain around the
      right hip, of 5 years duration. Computed tomography CT scan showed a multi
      loculated mass in the right iliopsoas muscle. On exploration, a hemorrhagic
      cystic mass was seen pressing on the femoral nerve. The lesion was excised and
      histological examination of the tissue showed features of endometriosis. The
      patient was treated by cyclic hormonal suppressive therapy for 3 months. Her pain
      and the flexion deformity of the hip resolved completely. Retroperitoneal
      endometriosis presenting with deformity and pain in the hip may mimic a psoas
      abscess. If the possibility of this diagnosis is entertained, inappropriate
      treatment may be avoided.

PMID- 17530118
TI  - Intra-articular lipoma causing snapping in the patellofemoral joint.
AB  - Intra-articular lipoma is an exceedingly rare diagnosis. We identified a lipoma
      that was seated in the retropatellar area and caused snapping of the patella
      during flexion of the knee joint. The tumor was easily and totally excised under
      arthroscopic guidance after the thin pedicle was cut.

PMID- 17530119
TI  - Gastric immature teratoma.
AB  - Gastric teratoma GT is a rare neoplasm which accounts for less than 1% of all
      teratomas in children. Little more than 100 cases of GT are reported in the
      literature out of which, about a dozen cases are of immature variety. We present
      a case of immature gastric teratoma in a 7-month-old male baby.

PMID- 17530120
TI  - Simultaneous bilateral multipuncture tubeless percutaneous nephrolithotomy in
      patient with orthotopic bladder substitution.
AB  - We report the successful treatment of a patient that presented with bladder
      tumor, bilateral multiple renal stones, right lower ureteral stone, and bilateral
      hydroureteronephrosis with progressively rising serum creatinine. Initially, he
      was managed by drainage of the upper tract by left percutaneous nephrostomy tube
      until serum creatinine dropped to normal value then he was managed by radical
      cystectomy and orthotopic bladder substitution. Three weeks later, he was
      subjected to simultaneous bilateral multi-puncture tubeless percutaneous
      nephrolithotomy. In addition, we report on the feasibility of opacification of
      the collecting system via ascending pouchogram by direct passage of the dye
      through the directly implanted ureters thus avoiding intravenous contrast
      injection.

PMID- 17530121
TI  - Cor triatriatum sinister.

PMID- 17530122
TI  - Malignant mesochymal tumor of the spermatic cord. A rare para testicular tumor.

PMID- 17530123
TI  - Pyopneumopericardium due to esophago-pericardial fistula in patient with
      tuberculous pericarditis.

PMID- 17530124
TI  - Death due to primary hyperparathyroidism.

PMID- 17530125
TI  - Ventricular septal rupture presenting with hyperosmolar hyperglycemic nonketotic
      coma.

PMID- 17530126
TI  - A forgotten complication following pancreatic resection. Visceral artery pseudo
      aneurysms.

PMID- 17530127
TI  - Isoniazid susceptibilities of Mycobacterium tuberculosis on blood agar.

PMID- 17530128
TI  - The role of fine needle aspiration cytology in the diagnosis of peripheral
      lymphadenopathy. An institutional experience of 83 cases.

PMID- 17530129
TI  - A life-sustaining single dose of recombinant activated factor VII for an Egyptian
      patient with hemorrhagic crisis.

PMID- 17530130
TI  - Ovarian hyper stimulation syndrome.

PMID- 17530131
TI  - Reliability of vascularized fibula in maintaining arthrodesis following extra
      articular wide excisions of malignant musculoskeletal tumors.

PMID- 17530132
TI  - Pulmonary lymphangioleiomyomatosis is easily mistaken for more common lung
      diseases.

PMID- 17530133
TI  - Correlation does not always show a causal relationship.

PMID- 17530134
TI  - Challenges in the critically ill child: a global vision.

PMID- 17530135
TI  - End-of-life care in children: the Brazilian and the international perspectives.
AB  - OBJECTIVE: To analyze the medical practices and the end-of-life care provided to
      children admitted to pediatric intensive care units in different parts of the
      globe. SOURCES: Articles on end-of-life care published during the last 20 years
      were selected from the PubMed, MEDLINE and LILACS databases, with emphasis on
      studies of death in pediatric intensive care units in Brazil, Latin America,
      Europe and North America, using the following keywords: death, bioethics,
      pediatric intensive care, cardiopulmonary resuscitation and life support
      limitation. SUMMARY OF THE FINDINGS: Publications on life support limitation
      (LSL) are concentrated in North America and Europe. In North American pediatric
      intensive care units there is a greater incidence of LSL (approximately 60%) than
      in Europe or Latin America (30-40%). These differences appear to be related to
      cultural, religious, legal and economic factors. Over the last decade, LSL in
      Brazilian pediatric intensive care units has increased from 6 to 40%, with do not
      resuscitate orders as the most common method. Also of note is the low level of
      family participation in the decision-making process. A recent resolution adopted
      by the Federal Medical Council (Conselho Federal de Medicina) regulated LSL in
      our country, demystifying a certain apprehension of a legal nature. The authors
      present a proposal for a protocol to be followed in these cases. CONCLUSIONS: The
      adoption of LSL with children in the final phases of irreversible diseases has
      ethical, moral and legal support. In Brazil, these measures are still being
      adopted in a timid manner, demanding a change in behavior, especially in the
      involvement of families in the decision-making process.

PMID- 17530136
TI  - Dengue and dengue hemorrhagic fever: management issues in an intensive care unit.
AB  - OBJECTIVES: To describe the epidemiology, clinical features and treatment of
      dengue fever and dengue shock syndrome. SOURCES: To prepare this review, a
      literature search was made on PubMed and on the World Health Organization (WHO)
      and PAHO websites using the terms dengue and dengue shock syndrome. This
      information was complemented with personal practice. SUMMARY OF THE FINDINGS:
      Dengue is the most important arthropod-borne viral disease of humans. Its
      presentation is protean and varies from an undifferentiated viral syndrome to
      hemorrhagic fever and severe shock. Dengue fever is a self-limiting, nonspecific
      illness characterized by fever, headache, myalgia, and constitutional symptoms.
      Its severe forms (hemorrhagic fever and shock syndrome) may lead to multisystem
      involvement and death. Early diagnosis, close monitoring for deterioration and
      response to treatment are necessary in all cases. WHO has provided a stepwise
      approach to management that is useful for milder forms and early shock. In the
      more severe forms aggressive fluid resuscitation and support for failing organs
      is necessary for the critically ill patient. Research addressing
      pathophysiological differences between dengue shock and septic shock, choice of
      fluids, inotropes and techniques of organ support are likely to yield benefits
      for the critically ill. CONCLUSIONS: There is no specific therapy for dengue
      infections. Good supportive care may be lifesaving, but ultimately initiatives
      aimed at vector control and prevention of mosquito bites may provide the greatest
      benefits.

PMID- 17530137
TI  - Pharmacologic support of infants and children in septic shock.
AB  - OBJECTIVES: Septic shock (SS) is a frequent cause for admission to the pediatric
      intensive care unit, requiring prompt recognition and intervention to improve
      outcome. Our aim is to review the relevant literature related to the diagnosis
      and management of SS and present a sequential management for its treatment.
      SOURCES: Non-systematic review of medical literature using the MEDLINE database.
      Articles were selected according to their relevance to the objective and
      according to the authors' opinions. SUMMARY OF THE FINDINGS: The outcome of
      sepsis and SS is dependent on the early recognition and implementation of time
      sensitive goal-directed therapies. These include rapid aggressive fluid
      resuscitation followed by a well-designed pharmacotherapy. The goals of the
      resuscitation are the restoration of microcirculation and improved organ tissue
      perfusion. Clinical and laboratory markers are needed to assess the adequacy of
      the treatments. Altered pharmacokinetic and pharmacodynamic responses dictate
      that vasoactive agents should be adjusted to achieve the predetermined goals. In
      initial resuscitation with isotonic solutions (> 60 mL/kg), either crystalloid
      (normal saline) or colloid infusion could be used. Despite adequate fluid
      resuscitation, if: (a) wide pulse pressure, low blood pressure, or bounding
      pulses (high cardiac output, low systemic vascular resistance--SVR) are present,
      norepinephrine should be considered; (b) prolonged capillary refill, weak pulses,
      narrow pulse pressure, normotensive (low cardiac output, high SVR), dopamine,
      epinephrine or dobutamine should be considered. Adjunctive therapy with stress
      dose of corticosteroid is indicated in selected populations. CONCLUSIONS: Septic
      shock hemodynamics is a changing process that requires frequent assessment and
      therapeutic adjustments.

PMID- 17530138
TI  - New guidelines for the clinical management of febrile neutropenia and sepsis in
      pediatric oncology patients.
AB  - OBJECTIVES: To provide a foundation for the diagnostic, prophylactic and
      therapeutic management of febrile neutropenia and sepsis in children with
      oncological diseases, with special attention to new protocols and guidelines.
      SOURCES: A review of the scientific literature utilizing an electronic
      bibliographic search on MEDLINE, Medscape, SciELO, Google, Cochrane and PubMED
      using the keywords febrile, neutropenic, cancer, children, sepsis, intensive,
      care. Articles published between 1987 and 2007 were selected, with preference
      given to review articles, protocols, systematic reviews, epidemiological studies,
      task force recommendations and phase III clinical trials. Consensus documents
      published by the Infectious Diseases Society of America, the Center for Diseases
      Control and the Infectious Diseases Working Party of the German Society of
      Hematology and Oncology, in addition to the recommendations of the World
      Federation of Pediatric Intensive and Critical Care Societies and Society of
      Critical Care Medicine, were also reviewed. SUMMARY OF THE FINDINGS: The use of
      aggressive chemotherapy regimens, bone marrow transplantation and intensive care
      resources have increased the survival rates of children with cancer and also
      their infectious morbidity, with septic complications as the principal cause of
      mortality. Several risk factors have been identified, such as neutropenia,
      oncology type, clinical signs and inflammatory response markers (polymerase chain
      reaction, procalcitonin) and also increased resistance to antimicrobials and
      antifungal agents. Protocols for risk classification, diagnosis and treatment
      should be established at each service, taking into account the microbiological
      flora of each population. Pediatric intensive care has increased the short and
      long-term survival of these patients. CONCLUSIONS: Oncology patients are
      particularly vulnerable to infectious complications. Early identification and
      treatment are fundamental to improving survival rates.

PMID- 17530139
TI  - Analgesia and sedation in children: practical approach for the most frequent
      situations.
AB  - OBJECTIVES: To review the most frequent recommendations, doses and routes of
      administration of sedatives, analgesics, and muscle relaxants in children, as
      well as the methods for monitoring the level of sedation. SOURCES: Review of the
      literature using the MEDLINE database and review of the experience in pediatric
      intensive care units. SUMMARY OF THE FINDINGS: The continuous administration of
      analgesics and sedatives prevents the development of undersedation and is less
      demanding in terms of care than intermittent administration. Midazolam is the
      most commonly used drug for continuous sedation of critically ill children.
      Opioid derivatives and nonsteroidal anti-inflammatory drugs are the most widely
      used analgesics in critically ill children. Opioids combined with
      benzodiazepines, given in continuous infusion, are the drugs of choice in
      mechanically ventilated children, especially morphine and fentanyl. The use of
      protocols and monitoring through clinical scores and objective methods (e.g.
      bispectral index) allow adjusting medication more appropriately, preventing
      oversedation, undersedation, and the withdrawal syndrome. Non-pharmacological
      interventions, such as music therapy, noise control, adequate use of light,
      massage, conversation with the patient, are ancillary measures that help children
      to adapt to the adverse hospital environment. CONCLUSIONS: Sedation should be
      tailored to each child for each specific situation. Protocols that facilitate the
      correct selection of drugs, their appropriate administration and careful
      monitoring improve the quality of sedation and analgesia and avoid their adverse
      effects.

PMID- 17530140
TI  - Tracheal intubation.
AB  - OBJECTIVE: To review current concepts related to the procedure of tracheal
      intubation in children. SOURCES: Relevant articles published from 1968 to 2006
      were selected from the MEDLINE, LILACS and SciELO databases, using the keywords
      intubation, tracheal intubation, child, rapid sequence intubation and pediatric
      airway. SUMMARY OF THE FINDINGS: Airway management in children is related to
      their physiology and anatomy, in addition to specific factors (inherent
      pathological conditions, such as malformations or acquired conditions) which have
      a decisive influence on success. Principal indications are in order to maintain
      the airway patent and to control ventilation. Laryngoscopy and tracheal
      intubation cause cardiovascular alterations and affect airway reactivity. The use
      of tubes with cuffs is not prohibited, as long as the correct size for the child
      is chosen. A difficult airway can be identified against the Mallampati scale and
      by direct laryngoscopy. Rapid sequence intubation is being recommended more and
      more often in pediatrics, since it facilitates the procedure and presents fewer
      complications. Tracheal intubation should be carried out in an adequate manner in
      special circumstances (eaten recently, neurological dysfunction, unstable spinal
      column, upper airway obstruction, laryngotracheal injuries, injuries to the
      eyeball). Extubation should be meticulously planned, since there is chance of
      failure and a need for reintubation. CONCLUSIONS: Tracheal intubation of children
      requires knowledge, skill and experience, since, if the procedure is carried out
      by inexperienced pediatricians, it can result in life-threatening complications.

PMID- 17530141
TI  - Continuing education for healthcare professionals: time to prove its worth.
AB  - With escalating financial pressures being placed upon health services, it becomes
      increasingly hard to justify spending on education and training. At the same
      time, however, primary care practitioners are being expected to take on new roles
      in the management of long term conditions which were once the domain of their
      secondary care colleagues. This Discussion paper highlights the importance of
      expanding the evidence base for healthcare professional training - particularly
      in terms of its positive effects on patient care - and emphasises how important
      it is that those responsible for commissioning training continue to see the
      importance of doing so. It cites a randomised controlled trial of education in
      the primary care management of rhinitis as an example of the way in which
      healthcare professional education can improve patients' quality of life. Without
      continued investment in healthcare professionals' education, the vision of high
      quality, guideline-driven, evidence-based health care will never come to
      fruition.

PMID- 17530142
TI  - Asthma: 1987-2007. What have we achieved and what are the persisting challenges?
AB  - Despite an increasing prevalence of asthma, enormous advances have been made in
      our understanding and management of asthma over the last 20 years. Work begun two
      or three decades ago demonstrated the inflammatory nature of asthma, emphasised
      the need for regular treatment, and introduced the goal of maintaining normal
      lung function. More recent work demonstrated the benefits of adding a long-acting
      inhaled beta-agonist to low-dose inhaled steroids as an alternative to escalating
      the steroid dosage. More recently still, studies and regulatory approval have led
      to the possibility of the same inhaler being used for maintenance therapy and for
      relief. However, these new ways of using old medicines, along with some new
      medicines such as omalizumab, should not detract us from looking beyond the
      prescription. The challenges facing us now are to determine why the prevalence of
      asthma has increased so dramatically, and in the absence of a cure how we can
      best help increasing numbers of people with asthma benefit from the treatment
      which is available. This will involve a much more aggressive implementation of
      advice regarding self-management education and a restructuring of health services
      to provide a service that is cognisant of the fact that, like us, patients are
      increasingly busy - and if they are to benefit from regular review, that review
      needs to be offered at a convenient time and by convenient methods.

PMID- 17530143
TI  - The impact of the UK General Practice Airways Group (GPIAG) - an international
      perspective.
AB  - The impact of the UK General Practice Airways Group (GPIAG) over the past 20
      years is discussed from an international perspective. The formation of the
      International Primary Care Respiratory Group (IPCRG) following the GPIAG
      conference in 2000, and the role of the Primary Care Respiratory Journal in
      publishing high quality primary care respiratory research, have been seminal
      elements in the development of the discipline of primary care respiratory
      medicine internationally. Research, guidelines development, education, and
      advocacy, are other areas where the GPIAG has provided a model or shown the way.
      At a more pragmatic level, the experience of the GPIAG in building a relationship
      with sponsors and in negotiating the regulatory maze in order to establish an
      incorporated legal company and charity saved the IPCRG much anguish. The
      differing roles of national and international organisations are contrasted to
      illustrate the constructive tension that has impacted on both organisations over
      the past five years. The IPCRG has built on the foundations of national
      organisations, particularly the GPIAG, but is charting the way internationally to
      support the delivery of better health outcomes for people with respiratory
      disease.

PMID- 17530144
TI  - The properties of inhaled corticosteroids: similarities and differences.
AB  - Inhaled corticosteroids remain the most important therapy for chronic asthma in
      both adults and children. As all inhaled corticosteroids act by binding to a
      common glucocorticoid receptor there is little evidence of any real difference in
      clinical efficacy between the different inhaled corticosteroids. The main
      potential differences are in their propensity to cause side effects. Local side
      effects such as a hoarse voice do occur in a proportion of adults and there is
      some limited evidence that ciclesonide may cause less local side effects. In
      adults there is little evidence for clinically important systemic side effects
      from doses of inhaled steroids below 800 mcg/day (beclomethasone equivalent).
      Above this dose a proportion of patients may show some adrenocortical
      suppression, though it is unlikely to be of clinical importance. Data on bone
      mineral density and fracture rates is discrepant, but an overview would suggest
      that below 800 mcg/day there is no increase in fracture risk whereas above this
      dose there might be an increased fracture risk. The properties of ciclesonide
      would suggest that it has less propensity for systemic side effects, but large
      long term studies are needed to confirm this. In children using inhaled steroids
      at above-licensed doses reductions in short-term growth can occur, but there is
      little evidence for reductions in long-term growth at normal doses. At above
      licensed doses, biochemical adrenocortical suppression can occur with some
      unusual but documented cases of clinical Addisonian crisis. Limited evidence in
      paediatric age groups would suggest that ciclesonide may have some advantage
      although it is not as yet licensed in all countries for paediatric use. Data on
      differences in side effects between normal and asthmatic patients, and between
      asthmatic patients with near-normal lung function compared to those with impaired
      lung function, indicate that inhaled corticosteroids (particularly fluticasone)
      are absorbed more in those with normal lung function; this strongly supports
      stepping down the inhaled steroid dose when asthma is controlled - as is
      recommended in asthma guidelines.

PMID- 17530145
TI  - Diagnosis of preschool asthma: parents' comments and typical phrases may ease
      history-taking.

PMID- 17530146
TI  - What standards and terms of employment should respiratory practitioners with a
      special interest expect from an employing organisation?
AB  - The UK Department of Health (DoH), with input from with the Royal College of
      General Practitioners and UK General Practice Airways Group (GPIAG), has drawn up
      guidelines for the appointment of General Practitioners or other Practitioners
      with a Special Interest (GPwSIs or PwSIs, respectively) in respiratory medicine.
      This Discussion paper is based on the deliberations of a GPIAG-organised multi
      professional Working Party held in November 2005. It highlights the three key
      roles of respiratory GPwSIs/PwSIs, and it aims to provide existing and potential
      specialist practitioners with a checklist of specific points to consider when
      drawing up a contract with their employing authority. Whilst this system is
      particular to the provision of primary care in the UK, other countries may choose
      to follow this model.

PMID- 17530147
TI  - A case of bronchial aspiration: the importance of early diagnosis and clinical
      suspicion.
AB  - We present a case of foreign body aspiration, the diagnosis of which was delayed
      until two months after the event. This case highlights the importance of a
      detailed clinical history in establishing the diagnosis of aspiration and how
      this was complicated by direct visualization via bronchoscopy which suggested a
      possible diagnosis of bronchial carcinoma. Subsequent histological analysis
      confirmed a diagnosis of Brazil nut aspiration, which ultimately required
      surgical extraction through a rigid endoscope.

PMID- 17530148
TI  - The estimated prevalence of chronic obstructive pulmonary disease in a general
      practice population.
AB  - OBJECTIVE: To estimate the prevalence of chronic obstructive pulmonary disease
      (COPD) in a general practice population in the UK. METHOD: Four postal
      respiratory questionnaire surveys were carried out between 1993 and 2001.
      Subjects from the 2001 study were invited for spirometry if they were aged 30
      years or more, had indicated that they were 'ever smokers' in any of the surveys,
      and/or had been considered to have likely obstructive airways disease on the
      basis of their replies to the 2001 questionnaire. RESULTS: 2646 subjects were
      invited for spirometry of whom 871 (32.9%) attended. Results were available for
      825 participants. 163 of these subjects were categorised as having COPD. The
      estimated prevalence in the whole population was 4.1% with the highest prevalence
      (14.7%) in those aged 60-69 years. In those aged over 40 years it was 9.6%.
      CONCLUSION: This study suggests that the prevalence of COPD is much higher than
      the previous estimates of between 1 and 2%.

PMID- 17530149
TI  - The UK General Practice Airways Group (GPIAG): its formation, development, and
      influence on the management of asthma and other respiratory diseases over the
      last twenty years.
AB  - This article describes the formation and development of the UK General Practice
      Airways Group (GPIAG), from its inception as a small respiratory special-interest
      group founded by six general practitioners in 1987 through to its transformation
      into the largest primary care specialist society in the UK. It highlights the
      historical context in which the GPIAG was founded - at a time when there was
      increasing concern about under-treatment and under-diagnosis of asthma in primary
      care - and describes the way in which its foundation was one of the major
      influences that led to profound innovation in the primary care management of
      respiratory disease as well as changes across the primary/secondary care
      interface. The GPIAG is now a registered charity, has an expanding membership,
      and has acquired a high profile both nationally and internationally as an
      advisory body on policy and strategy for the management of respiratory disease in
      primary care. This review is a 20th anniversary tribute not only to those who
      have contributed to the success of the GPIAG over the last twenty years, but also
      to its current membership who enable the GPIAG to continue working towards its
      charitable aim of "optimal respiratory care for all."

PMID- 17530150
TI  - Cancer in people with depression or anxiety: record-linkage study.
AB  - BACKGROUND: It has been suggested that the risk of cancer may be higher in people
      with psychological disorders, like depression and anxiety, than in the general
      population. AIMS: To determine cancer risk in cohorts of people with depression
      or anxiety, compared with that in a control cohort. METHOD: Analysis of linked
      statistical records of hospital admission and mortality. RESULTS: Lung cancer was
      more common in those with depression (risk ratio 1.36, 95% confidence intervals
      1.19-1.54) or anxiety (1.29, 1.12-1.48) than in others. Excluding lung cancer,
      the risk ratio for all other cancers combined was 0.98 (0.92-1.04) in the
      depression cohort and 1.01 (0.95-1.07) in the anxiety cohort. There was a
      significant association, in the short-term only, between depression, anxiety and
      the subsequent diagnosis of brain tumours. CONCLUSIONS: With the exception of
      lung and brain tumours, cancer risk was not increased in people with depression
      or anxiety.

PMID- 17530151
TI  - Prevalence and predictors of post-traumatic stress disorder (PTSD) in physically
      injured victims of non-domestic violence. A longitudinal study.
AB  - BACKGROUND: Victims of violent assault experience diverse post-event emotional
      problems such as post-traumatic stress disorder (PTSD), and they may have
      multiple emotional problems. The aim of the present study was to evaluate the
      prevalence and predictors of PTSD in a longitudinal design. METHODS: The levels
      of physical injury, perceived life threat, prior experience of violence,
      peritraumatic dissociation (PD), acute PTSD, perceived self-efficacy and
      perceived social support are considered possible predictors. This study had a
      single group (N = 70), longitudinal design with three repeated measures over a
      period of 12 months. Questionnaires used were: Impact of Event Scale-15 and 22
      (IES-15 and 22), Post-Traumatic Symptom Scale-10 (PTSS-10), Peritraumatic
      Dissociation (PD) 7-item self-report measure, Social Provisions Scale (SPS) and
      Generalized Self-Efficacy scale (GSE). RESULTS: Results showed a high prevalence
      and severity of PTSD on all outcomes, for instance 31% scored as probable PTSD
      cases and 14% as risk level cases by IES-15 at T3. Either injury severity or
      prior experience of being a victim of violence predicted PTSD in this study.
      Early PTSD predicted subsequent PTSD, and perceived life threat was a predictor
      of PD. Furthermore, lack of perceived social support was a predictor of PTSD
      symptoms at T3. In addition, low perceived self-efficacy was a predictor of PTSD
      and influenced perceived social support at T1. CONCLUSIONS: Our results showed
      that experience of non-domestic violence may cause serious chronic emotional
      problems, and therefore it is important to be aware of early symptoms indicating
      needs for special follow-ups.

PMID- 17530152
TI  - The mental health effects of multiple work and family demands. A prospective
      study of psychiatric sickness absence in the French GAZEL study.
AB  - BACKGROUND: Individuals who experience work stress or heavy family demands are at
      elevated risk of poor mental health. Yet, the cumulative effects of multiple work
      and family demands are not well known, particularly in men. METHODS: We studied
      the association between multiple work and family demands and sickness absence due
      to non-psychotic psychiatric disorders in a longitudinal study conducted among
      members of the French GAZEL cohort study (8,869 men, 2,671 women) over a period
      of 9 years (1995-2003). Work stress and family demands were measured by
      questionnaire. Medically certified psychiatric sickness absence data were
      obtained directly from the employer. Rate ratios (RRs) of sickness absence were
      calculated using Poisson regression models, adjusting for age, marital status,
      social support, stressful life events, alcohol consumption, body mass and
      depressive symptoms at baseline. RESULTS: Participants simultaneously exposed to
      high levels of work and family demands (> or =2 work stress factors and > or =4
      dependents) had significantly higher rates of sickness absence due to non
      psychotic psychiatric disorders than participants with lower levels of demands
      (compared to participants exposed to 0-1 work stress factors and with 1-3
      dependents, age-adjusted rate ratios were 2.37 (95% CI 1.02-5.52) in men and 6.36
      (95% CI 3.38-11.94) in women. After adjusting for baseline socio-demographic,
      behavioral and health characteristics, these RRs were respectively reduced to
      1.82 (95% CI 0.86-3.87) in men, 5.04 (95% CI 2.84-8.90) in women. The effect of
      multiple work and family demands was strongest for sickness absence due to
      depression: age-adjusted RRs among participants with the highest level of work
      and family demands were 4.70 (1.96-11.24) in men, 8.57 (4.26-17.22) in women;
      fully adjusted RRs: 3.55 (95% CI 1.62-7.77) in men, 6.58 (95%CI 3.46-12.50) in
      women. CONCLUSIONS: Men and women simultaneously exposed to high levels of work
      stress and family demands are at high risk of experiencing mental health
      problems, particularly depression.

PMID- 17530153
TI  - Nip, tuck and rejuvenate; the latest frontier for the gynecologic surgeon.

PMID- 17530154
TI  - Does antenatal pelvic floor muscle training affect the outcome of labour? A
      randomised controlled trial.
AB  - It is thought that antenatal pelvic floor muscle training (PFMT) might produce a
      strong pelvic floor resulting in prolonged labour, whilst some believe it
      produces well-controlled muscles that facilitate rotation of the foetal head and
      shortens the duration of labour. This secondary analysis (of a previously
      published randomised controlled trial) assesses the labour and delivery details
      of 268 primigravidae who were originally randomised at approximately 20 weeks
      gestation to supervised PFMT or a control group. Between the two groups, there
      was no difference in the duration of the second stage of labour or in the need
      for instrumental delivery. PFMT does not appear to facilitate or obstruct labour.

PMID- 17530155
TI  - Hypovitaminosis D and secondary hyperparathyroidism in the elderly: risk factors
      for hip fracture or markers of frailty?

PMID- 17530156
TI  - Simulation-based cost-utility analysis of population screening-based alendronate
      use in Switzerland.
AB  - A simulation model adopting a health system perspective showed population-based
      screening with DXA, followed by alendronate treatment of persons with
      osteoporosis, or with anamnestic fracture and osteopenia, to be cost-effective in
      Swiss postmenopausal women from age 70, but not in men. INTRODUCTION: We assessed
      the cost-effectiveness of a population-based screen-and-treat strategy for
      osteoporosis (DXA followed by alendronate treatment if osteoporotic, or
      osteopenic in the presence of fracture), compared to no intervention, from the
      perspective of the Swiss health care system. METHODS: A published Markov model
      assessed by first-order Monte Carlo simulation was refined to reflect the
      diagnostic process and treatment effects. Women and men entered the model at age
      50. Main screening ages were 65, 75, and 85 years. Age at bone densitometry was
      flexible for persons fracturing before the main screening age. Realistic
      assumptions were made with respect to persistence with intended 5 years of
      alendronate treatment. The main outcome was cost per quality-adjusted life year
      (QALY) gained. RESULTS: In women, costs per QALY were Swiss francs (CHF) 71,000,
      CHF 35,000, and CHF 28,000 for the main screening ages of 65, 75, and 85 years.
      The threshold of CHF 50,000 per QALY was reached between main screening ages 65
      and 75 years. Population-based screening was not cost-effective in men.
      CONCLUSION: Population-based DXA screening, followed by alendronate treatment in
      the presence of osteoporosis, or of fracture and osteopenia, is a cost-effective
      option in Swiss postmenopausal women after age 70.

PMID- 17530157
TI  - Standardised quantitative morphometry: a modified approach for quantitative
      identification of prevalent vertebral deformities.
AB  - Our approach for the quantitative identification of vertebral deformity
      (standardised quantitative morphometry, SQM) reduces problems associated with
      obtaining reference intervals from populations with high prevalence of fracture.
      In women with osteoporosis, agreement with radiological diagnosis (surrogate gold
      standard) was better for SQM than QM using the Eastell-Melton method.
      INTRODUCTION: Use of reference intervals for quantitative vertebral morphometry
      (QM) derived by statistical trimming can be problematic in reference populations
      with high prevalence of deformity. We have developed a modified approach known as
      standardised quantitative morphometry (SQM), whereby vertebral height is
      standardised to eliminate variation between individuals. The aims of this study
      were to compare SQM to QM (Eastell-Melton method) for identification of prevalent
      vertebral deformities, using qualitative radiological diagnosis as the gold
      standard, and automate the process. METHODS: Our study populations were a clinic
      based sample of 80 women ages 48 to 87 years with a high prevalence of vertebral
      deformity and a general practice (GP)-based sample of 372 women ages 50 to 85
      years. Agreement with the gold standard was tested for SQM and QM. RESULTS:
      Agreement was better for SQM (kappa = 0.80) than for QM (kappa = 0.14) in the
      clinic sample using clinic-based reference data. The agreement was improved for
      QM using the GP-based reference data, kappa = 0.63. In the GP population,
      agreement was good for both SQM and QM (kappa = 0.59 and 0.54 respectively).
      CONCLUSIONS: In our population with a high prevalence of vertebral fracture, SQM
      performs better than the Eastell-Melton method.

PMID- 17530158
TI  - Electrophysiological studies in Xenopus oocytes for the opening of Escherichia
      coli SecA-dependent protein-conducting channels.
AB  - Protein translocation in Escherichia coli requires protein-conducting channels in
      cytoplasmic membranes to allow precursor peptides to pass through with adenosine
      triphosphate (ATP) hydrolysis. Here, we report a novel, sensitive method that
      detects the opening of the SecA-dependent protein-conducting channels at the
      nanogram level. E. coli inverted membrane vesicles were injected into Xenopus
      oocytes, and ionic currents were recorded using the two-electrode voltage clamp.
      Currents were observed only in the presence of E. coli SecA in conjunction with
      E. coli membranes. Observed currents showed outward rectification in the presence
      of KCl as permeable ions and were significantly enhanced by coinjection with the
      precursor protein proOmpA or active LamB signal peptide. Channel activity was
      blockable with sodium azide or adenylyl 5'-(beta,gamma-methylene)-diphosphonate,
      a nonhydrolyzable ATP analogue, both of which are known to inhibit SecA protein
      activity. Endogenous oocyte precursor proteins also stimulated ion current
      activity and can be inhibited by puromycin. In the presence of puromycin,
      exogenous proOmpA or LamB signal peptides continued to enhance ionic currents.
      Thus, the requirement of signal peptides and ATP hydrolysis for the SecA
      dependent currents resembles biochemical protein translocation assay with E. coli
      membrane vesicles, indicating that the Xenopus oocyte system provides a sensitive
      assay to study the role of Sec and precursor proteins in the formation of protein
      conducting channels using electrophysiological methods.

PMID- 17530159
TI  - The polarity of lipid-exposed residues contributes to the functional differences
      between Torpedo and muscle-type nicotinic receptors.
AB  - A comparison between the Torpedo and muscle-type acetylcholine receptors (AChRs)
      reveals differences in several lipid-exposed amino acids, particularly in the
      polarity of those residues. The goal of this study was to characterize the role
      of eight lipid-exposed residues in the functional differences between the Torpedo
      and muscle-type AChRs. To this end, residues alphaS287, alphaC412, betaY441,
      gammaM299, gammaS460, deltaM293, deltaS297 and deltaN305 in the Torpedo AChR were
      replaced with those found in the muscle-type receptor. Mutant receptor expression
      was measured in Xenopus oocytes using [(125)I]-alpha-bungarotoxin, and AChR ion
      channel function was evaluated using the two-electrode voltage clamp. Eight
      mutant combinations resulted in an increase (1.5- to 5.2-fold) in AChR
      expression. Four mutant combinations produced a significant 46% decrease in the
      ACh 50% inhibitory concentration (EC(50)), while three mutant combinations
      resulted in 1.7- to 2-fold increases in ACh EC(50). Finally, seven mutant
      combinations resulted in a decrease in normalized, ACh-induced currents. Our
      results suggest that these residues, although remote from the ion channel pore,
      (1) contribute to ion channel gating, (2) may affect trafficking of AChR into
      specialized membrane domains and (3) account for the functional differences
      between Torpedo and muscle-type AChR. These findings emphasize the importance of
      the lipid-protein interface in the functional differences between the Torpedo and
      muscle-type AChRs.

PMID- 17530160
TI  - Effect of spirulina maxima on the haloperidol induced tardive dyskinesia and
      oxidative stress in rats.
AB  - Haloperidol is a widely used neuroleptic drug for the treatment of acute and
      chronic psychosis. The use of haloperidol is limited by extrapyramidal movement
      disorders such as Parkinsonism, akathesia, dystonia, and tardive dyskinesia (TD).
      Treatment with haloperidol increases oxyradicals which are implicated in TD.
      Spirulina is widely used as nutritional supplement rich in proteins and
      antioxidants. The present study is proposed to study the effect of spirulina on
      haloperidol induced TD and oxidative stress by studying TD, various enzymatic and
      nonenzymatic antioxidants and lipid peroxidation. Haloperidol 1 mg/kg/i.p was
      used to induce vacuous chewing movements in rats. Spirulina maxima suspended in
      1% between 80 at a dose of 45, 90 and 180 mg/kg were administered by gavage along
      with haloperidol from 21st day to 49th day of treatment. Spirulina
      supplementation at a dose of 180 mg/kg significantly improved enzymatic and
      nonenzymatic antioxidants and decreased the tardive dyskinesia induced by
      haloperidol. In conclusion, the results of present investigation suggest that
      spirulina decreases haloperidol induced oxidative stress and TD by many
      mechanisms as it is cocktail of antioxidants. On chronic use it may inhibit
      haloperidol induced reduced expression of DNA thereby increases the expression of
      enzymatic and nonenzymatic antioxidants and protects against oxidative stress
      induced neurodegeneration and TD.

PMID- 17530161
TI  - The impact of hyperactivity and leptin on recovery from anorexia nervosa.
AB  - In anorexia nervosa (AN), hyperactivity is observed in about 80% of patients and
      has been associated with low leptin levels in the acute stage of AN and in
      anorexia animal models. To further understand the importance of this correlation
      in AN, we investigated the relationship between hypoleptinaemia and hyperactivity
      in AN patients longitudinally and assessed their predictive value for recovery.
      Body weight, activity levels, and serum leptin levels were assessed in
      adolescents and adult AN patient groups at the start and during treatment, up to
      a year. In the adolescent group, initial leptin and activity levels were
      correlated. This negative correlation changes over time into a positive
      correlation with physiological recovery. Treatment outcome in both groups could
      be predicted by initial BMI and leptin levels but not by activity levels. No
      major relationship of activity with the course of recovery was detected,
      suggesting that in contrast to the acute stage of the disease, leptin and
      activity levels during the recovery process are dissociated.

PMID- 17530162
TI  - Medicine is a constant battlefield.

PMID- 17530165
TI  - Molecular phylogenetic analysis of Euphorbiaceae sensu stricto based on plastid
      and nuclear DNA sequences and ovule and seed character evolution.
AB  - A phylogenetic analysis of Euphorbiaceae sensu stricto is presented using
      sequences from rbcL, atpB, matK and 18S rDNA from 85 species and 83 genera. The
      combined analysis of four molecular markers resulted in only one most
      parsimonious tree and also generated new supported clades, which include
      Euphorbioideae + Acalyphoideae s.s., subclades A2 + A3, subclades A5 + A6 and a
      clade uniting subclades A2-A8 within Acalyphoideae s.s. A palisadal exotegmen is
      a possible synapomorphy for all the Euphorbiaceae, except for the subfamily
      Peroideae. The presence of vascular bundles in the inner integument and a thick
      inner integument were shown to be synapomorphies for the clade of inaperturate
      and articulated crotonoids and for the large clade of Euphorbioideae,
      Acalyphoideae s.s., inaperturate and articulated crotonoids, respectively.
      Characters of the aril and vascular bundles in the outer integument are
      discussed. The selected embryological characters were seen to be highly
      correlated with the molecular phylogeny. When the results of molecular
      phylogenetic analysis of a previous study and this study were adjusted along with
      the selected embryological characters, all clades within Euphorbiaceae were
      supported except for a clade comprising Euphorbioideae + Acalyphoideae s.s. +
      inaperturate crotonoids + articulated crotonoids + Adenoclineae s.l. and a clade
      uniting subclades A4-A8 within Acalyphoideae s.s.

PMID- 17530166
TI  - Breakdown of distyly in a tetraploid variety of Ophiorrhiza japonica (Rubiaceae)
      and its phylogenetic analysis.
AB  - We examined the floral morph of tetraploid Ophiorrhiza japonica Blume var.
      amamiana Hatus. and diploid O. japonica var. japonica to elucidate the
      association of distyly and ploidy levels. Chloroplast DNA phylogeny was
      reconstructed to determine the number of tetraploidization events and floral
      morph shifts in O. japonica. All individuals of O. japonica var. amamiana proved
      to be long-homostylous, whereas O. japonica var. japonica was distylous with
      typical long- and short-styled flowers. Distyly is related to the ploidy level.
      The bagging treatment of flowers indicated that O. japonica var. amamiana is self
      compatible and potentially automatically self-pollinating. In cpDNA sequencing
      analysis, no haplotype was shared between the two varieties. The cpDNA haplotype
      network displayed the monophyly of O. japonica var. amamiana, suggesting a single
      origin of this variety. Hence, both tetraploidization and the breakdown of
      distyly to homostyly in O. japonica var. amamiana likely occurred just once.
      Because O. japonica var. amamiana having the morphological and cytological entity
      is recognized as a single lineage and clearly separated from O. japonica var.
      japonica, this variety can be considered to be a distinct species. We therefore
      propose to raise O. japonica var. amamiana to the rank of species.

PMID- 17530167
TI  - Role of heregulin in human cancer.
AB  - Heregulin (HRG) is a soluble secreted growth factor, which, upon binding and
      activation of ErbB3 and ErbB4 transmembrane receptor tyrosine kinases, is
      involved in cell proliferation, invasion, survival and differentiation of normal
      and malignant tissues. The HRG gene family consists of four members: HRG-1, HRG
      2, HRG-3 and HRG-4, of which a multitude of different isoforms are synthesized by
      alternative exon splicing, showing various tissue distribution and biological
      activities. Disruption of the physiological balance between HRG ligands and their
      ErbB receptors is implicated in the formation of a variety of human cancers. The
      general mechanisms involved in HRG-induced tumorigenesis is discussed.

PMID- 17530168
TI  - On the structural definition of amyloid fibrils and other polypeptide aggregates.
AB  - Amyloid fibrils occur inside the human body, associated with ageing or a group of
      diseases that includes, amongst others, Alzheimer's disease, atherosclerosis and
      type II diabetes. Many natural polypeptide chains are able to form amyloid
      fibrils in vivo or in vitro, and this ability has been suggested to represent an
      inherent consequence of the chemical structure of the polypeptide chain. Recent
      literature has provided a wealth of information about the structure of
      aggregates, precipitates, amyloid fibrils and other types of fibrillar
      polypeptide assemblies. However, the biophysical meaning associated with these
      terms can differ considerably depending on the context of their usage. This
      overview presents a structural comparison of amyloid fibrils and other types of
      polypeptide assemblies and defines amyloid fibrils, based on structural
      considerations, as fibrillar polypeptide aggregates with a cross-beta
      conformation.

PMID- 17530169
TI  - Adult hippocampal neurogenesis: regulation by HIV and drugs of abuse.
AB  - New dentate granule cells are continuously generated from neural progenitor cells
      and integrated into the existing hippocampal circuitry in the adult mammalian
      brain through an orchestrated process termed adult neurogenesis. While the exact
      function remains elusive, adult neurogenesis has been suggested to play important
      roles in specific cognitive functions. Adult hippocampal neurogenesis is
      regulated by a variety of physiological and pathological stimulations. Here we
      review emerging evidence showing that HIV infection and several drugs of abuse
      result in molecular changes that may affect different aspects of adult
      hippocampal neurogenesis. These new findings raise the possibility that cognitive
      dysfunction in the setting of HIV infection or drug abuse may, in part, be
      related to alterations in hippocampal neurogenesis. A better understanding of how
      HIV and drugs of abuse affect both molecular and cellular aspects of adult
      neurogenesis may lead to development of more effective therapeutic interventions
      for these interlinked epidemics.

PMID- 17530170
TI  - Histone deacetylases: focus on the nervous system.
AB  - Neurodegenerative disease strikes millions worldwide and there is mounting
      evidence suggesting that underlying the onset and progression of these
      debilitating diseases is inappropriate neuronal apoptosis. Recent reports have
      implicated a family of proteins known as histone deacetylases (HDACs) in various
      neuronal processes including the neuronal death program. Initial headway in this
      field has been made largely through the use of broad-spectrum HDAC inhibitors. In
      fact, pharmacological inhibition of HDAC activity has been shown to protect
      neurons in several models of neurodegeneration. The observation that HDAC
      inhibitors can have opposing effects in different paradigms of neurodegeneration
      suggests that individual members of the HDAC protein family may play distinct
      roles that could depend on the specific cell type under study. The purpose of
      this review is to detail work involving the use of HDAC inhibitors within the
      context of neurodegeneration and examine the roles of individual HDAC members in
      the nervous system with specific focus on neuronal cell death.

PMID- 17530171
TI  - Conformational changes in a bacterial multidrug transporter are
      phosphatidylethanolamine-dependent.
AB  - LmrP is an electrogenic H(+)/drug antiporter that extrudes a broad spectrum of
      antibiotics. Five carboxylic residues are implicated in drug binding (Asp142 and
      Glu327) and proton motive force-mediated restructuring (Asp68, Asp128 and
      Asp235). ATR-FTIR (Attenuated Total Reflection - Fourier Transform Infrared) and
      tryptophan quenching experiments revealed that phosphatidylethanolamine (PE) is
      required to generate the structural intermediates induced by ionization of
      carboxylic residues. Surprisingly, no ionization-induced conformational changes
      were detectable in the absence of PE, suggesting either that carboxylic acid
      residues do not ionize or that ionization does not lead to any conformational
      change. The mean pKa of carboxylic residues evaluated by ATR-FTIR spectroscopy
      was 6.5 for LmrP reconstituted in PE liposomes, whereas the pKa calculated in the
      absence of PE was 4.6. Considering that 16 of the 19 carboxylic residues are
      located in the extramembrane loops, the pKa values obtained in the absence and in
      the presence of PE suggest that the interaction of the loop acid residues with
      the membrane interface depends on the lipid composition.

PMID- 17530172
TI  - What tangled webs they weave: Rho-GTPase control of angiogenesis.
AB  - The members of the Rho family of small GTPases are involved in an array of
      cellular processes, including regulation of the actin cytoskeleton, cell
      polarity, microtubule dynamics, membrane transport, and transcription factor
      activity. Recent findings have implicated the Rho-proteins as key regulators of
      angiogenesis, modulating a diversity of cellular processes, including vascular
      permeability, extracellular matrix remodeling, migration, proliferation,
      morphogenesis, and survival.

PMID- 17530173
TI  - Do cells think?
AB  - A microorganism has to adapt to changing environmental conditions in order to
      survive. Cells could follow one of two basic strategies to address such
      environmental fluctuations. On the one hand, cells could anticipate a fluctuating
      environment by spontaneously generating a phenotypically diverse population of
      cells, with each subpopulation exhibiting different capacities to flourish in the
      different conditions. Alternatively, cells could sense changes in the surrounding
      conditions - such as temperature, nutritional availability or the presence of
      other individuals - and modify their behavior to provide an appropriate response
      to that information. As we describe, examples of both strategies abound among
      different microorganisms. Moreover, successful application of either strategy
      requires a level of memory and information processing that has not been normally
      associated with single cells, suggesting that such organisms do in fact have the
      capacity to 'think'.

PMID- 17530174
TI  - Racial/ethnic differences in survival among elderly patients with a primary
      glioblastoma.
AB  - BACKGROUND: Few studies have assessed racial/ethnic differences in survival after
      primary glioblastoma diagnosis. We investigate these differences, incorporating
      information on White, Hispanics and Asians, as well as White, non-Hispanics and
      Blacks, among elderly individuals with a primary glioblastoma utilizing the
      population-based Surveillance, Epidemiology and End Results (SEER) Program
      Medicare linked database. METHODS: A total of 1,530 individuals diagnosed > = 66
      years of age from 6/1/91 to 12/31/99 in the SEER data were linked with Medicare
      information from 1/1/91 to 12/31/01. All individuals had Medicare Parts A and B
      and were non-HMO for 6 months before and 12 months after diagnosis to gather pre
      diagnosis co-morbidities and post-diagnosis first course of treatment. Survival
      differences by race/ethnicity and by race/ethnicity stratified by treatment type
      and/or median household income were examined using Kaplan-Meier and multivariable
      Cox proportional hazards models. RESULTS: Significant racial/ethnic differences
      existed between White, non-Hispanics and Blacks in marital status, income and
      SEER registry region for the entire US. In analysis limited to the West region,
      significant racial/ethnic differences existed for income only. Overall there were
      no differences in survival between White, non-Hispanics and Blacks, however, in
      analysis limited to the West region, Asians had a lower risk of death compared to
      White, non-Hispanics [HR = 0.67, 95% CI (0.43, 1.03)]. Asians who had multiple
      treatments also had a lower risk of death compared to White, non-Hispanics [HR =
      0.65, 95% CI (0.41, 1.01)]. CONCLUSIONS: Racial/ethnic differences in survival
      after primary glioblastoma diagnosis exist and may be partially explained by
      racial/ethnic differences in treatment and income.

PMID- 17530175
TI  - Prolonged and severe myelosuppression in two patients after low-dose temozolomide
      treatment- case study and review of literature.
AB  - Temozolomide is an alkylating agent used frequently in the management of gliomas.
      Although temozolomide is generally safe, rarely it can cause life threatening
      complications. Here we report the cases of two patients who developed prolonged
      and severe pancytopenia after low dose continuous temozolomide concurrently with
      cranial radiotherapy. The pancytopenia lasted two to six months. Both the
      patients were young, treatment naive, and had temozolomide treatment for only
      approximately four weeks.

PMID- 17530176
TI  - Trans-4-lodo,4'-boranyl-chalcone induces antitumor activity against malignant
      glioma cell lines in vitro and in vivo.
AB  - Chalcones are considered the precursors of flavonoids and have been identified as
      interesting compounds with antitumor properties. Boronic-chalcone derivatives are
      more toxic to breast cancer cells compared to normal breast cells. Here, we
      studied the antitumor activities of trans-4-lodo,4'-boranyl-chalcone (TLBC),
      which is a boronic-chalcone derivative, in several glioma cell lines. TLBC showed
      a dose-dependent inhibition with inhibitory concentration 50% value in the muM
      range (5.5-25.5 microM) in various glioma cell lines. Flow cytometric and western
      blot assay demonstrated that TLBC induced apoptosis independent of changes to the
      tumor suppressor p53. This cytotoxic effect was the caspase-dependent manner.
      Also, TLBC lowered levels of anti-apoptotic Bcl-2 and/or Bcl-X(L) protein in
      several of the cell lines. To examine the antitumor effect of TLBC in vivo, we
      used a malignant glioma xenograft model. This result showed that in the mice
      treated with TLBC at 20 mg/kg, mean tumor volume was reduced by 43.9% (P < 0.01)
      in comparison with the control group. Immunohistochemical and western blot
      analysis showed that Bcl-2 protein levels were decreased and Bax protein levels
      were slightly increased in the tumors injected with 20 mg/kg TLBC compared with
      the control tumors. Therefore, we conclude that TLBC may be a potential
      chemotherapeutic agent for human glioma.

PMID- 17530177
TI  - Pattern of recurrence in paediatric malignant glioma: an institutional
      experience.
AB  - BACKGROUND: The purpose of this retrospective study was to investigate the
      pattern of recurrence in paediatric malignant gliomas. MATERIAL AND METHODS: We
      reviewed the notes, diagnostic imaging and treatment charts of 30 consecutive
      paediatric patients (age less than 18 years at diagnosis, range 0.5-17 years)
      presenting with a malignant glioma presenting to the paediatric oncology unit at
      the Royal Marsden Hospital over a 10-year period. The imaging at the time of
      first relapse was compared with the initial diagnostic scans to define a relapse
      as local, marginal or distant. RESULTS: Median follow-up was 13 months (range 1
      99 months). Twenty-four of 30 patients (80%) showed evidence of progression with
      a median time to progression of 8.5 months (range 3-64 months). Thirteen out of
      24 patients developed local or marginal recurrences while 11/24 patients recurred
      at distant sites as site of first relapse (46%). CONCLUSION: Our series suggests
      that the pattern of relapses in paediatric malignant gliomas could be different
      from that reported in adult studies as we observed a significant incidence of
      distant relapses. Larger prospective series need to be conducted to investigate
      the clinico-biological characteristics of the population at high risk for
      leptomeningeal dissemination.

PMID- 17530178
TI  - Patients with metabolic syndrome exhibit higher platelet activity than those with
      conventional risk factors for vascular disease.
AB  - BACKGROUND: The metabolic syndrome is a matter of ongoing debate with regard to
      its existence, classification, clinical meaningfulness, and associated risks for
      vessel occlusion. Considering that persistent platelet activation is a
      cornerstone for the development of acute vascular events, and that patients with
      type 2 diabetes consistently exhibit high platelet activity, these
      characteristics may be critical for distinguishing and triageing specific
      features of metabolic syndrome among established risk factors for vascular
      disease. METHODS: We assessed the platelet activity by conventional aggregation,
      expression of major surface receptors by flow cytometry, and quantitatively by
      rapid bedside analyzers in 20 aspirin-naive patients with documented metabolic
      syndrome, and compared these with 20 untreated subjects with multiple
      cardiovascular risk factors. RESULTS: Closure time by the PFA-100 analyzer was
      significantly (P = 0.002) shorter in patients with metabolic syndrome indicating
      platelet inhibition under high shear conditions. Ultegra analyzer readings
      revealed increased fibrinogen binding (P = 0.0003) what in combination with the
      increased expression of PAC-1 (P = 0.32) strongly suggest activation of platelet
      glycoprotein IIb/IIIa receptor. Surface expression of CD107a (P = 0.014), and
      SPAN-12 (P = 0.003) were also higher in patients with metabolic syndrome. In
      contrast, platelet aggregation induced by collagen or ADP, CD31, CD41, CD42b,
      CD51/61, CD62p, CD63, CD154, CD165, so as formation of platelet-monocyte
      aggregates, PAR-1 thrombin receptor, and thrombospondin did not differ between
      groups. CONCLUSION: Patients with metabolic syndrome exhibited a higher degree of
      platelet activation than subjects with conventional risk factors for vascular
      disease. Conceptually, applying adequate antiplatelet strategies may reduce the
      risk of acute thrombotic events in these patients. Further prospective studies
      exploring this notion are encouraged.

PMID- 17530179
TI  - Novel recombination system using Cre recombinase alpha complementation.
AB  - A major limitation for the use of Cre recombinase is its toxicity and a lack of
      temporal control over its activity. We have developed a new recombination system
      using Cre recombinase alpha-complementation. Cre recombinase was divided and one
      fragment (beta) was introduced into cells between two loxP sites with a CMV
      promoter in the upstream. The gene of interest (EGFP) was positioned just
      downstream of this construct. Cre recombinase activity was recovered by adding
      the other part of the molecule (alpha) to cells as a protein fragment, as
      evidenced by the expression of EGFP under the control of the CMV promoter. The
      activity of fragmented cre reached 68% of that of the wild type enzyme at 1
      microM alpha-protein.

PMID- 17530180
TI  - A novel tissue-specific plantain beta-1,3-glucanase gene that is regulated in
      response to infection by Fusarium oxysporum fsp. cubense.
AB  - A new full-length beta-1,3-glucanase cDNA, MpGlu, was isolated from a plantain
      (Musa paradisica) by the rapid amplification of cDNA ends (RACE) technique.
      Recombinant GST-MpGlu protein, expressed in E. coli, hydrolyzed (1-->3),(1-->6)
      beta-glucan of Laminaria digitata and inhibited the growth of Fusarium oxysporum
      fsp. cubense (race 4) suggesting that it is a beta-1,3-glucanase. Southern blot
      analysis indicated that there is one copy of MpGlu in the plantain genome. MpGlu
      gene expression was detected in plantain leaves, peel, and pulp by RT-PCR.
      Northern blot analysis revealed that the expression of MpGlu was up-regulated by
      Fusarium infection. Subcellular localization analysis indicated that 28 residues
      at the N-terminal end are necessary for extracellular secretion, while 32
      residues at the C-terminal end are necessary to target the protein into vacuoles.

PMID- 17530181
TI  - Cloning, expression and characterization of a Baeyer-Villiger monooxygenase from
      Pseudomonas putida KT2440.
AB  - The gene encoding a Baeyer-Villiger monooxygenase and identified in Pseudomonas
      putida KT2440 was cloned and functionally expressed in Escherichia coli. The
      highest yield of soluble protein could be achieved by co-expression of molecular
      chaperones. In order to determine the substrate specificity, biocatalyses were
      performed using crude cell extract, growing and resting cells. Examination of
      aromatic, cyclic and aliphatic ketones revealed a high specificity towards short
      chain aliphatic ketones. Interestingly, some open-chain ketones were converted to
      the alkylacetates, while for others formation of the ester products with oxygen
      on the other side of the keto group could also be detected yielding the
      corresponding methyl or ethyl esters.

PMID- 17530182
TI  - Two new dialkoxycarbonylated nucleosides obtained through a regioselective
      enzymatic alcoholysis.
AB  - Two new compounds, 2',3'-di-O-ethoxycarbonyluridine and 2',3'-di-O
      ethoxycarbonylinosine, were obtained through a Candida antarctica lipase B
      catalysed regioselective ethanolysis of the corresponding trialcoxycarbonylated
      nucleosides with benzyl alcohol in 1,4-dioxane at 30 degrees C.

PMID- 17530183
TI  - Automated backbone and side-chain assignment of mitochondrial matrix cyclophilin
      D.

PMID- 17530184
TI  - Evaluation of the kinetic properties of the folate transport system in intestinal
      absorptive epithelium during experimental ethanol ingestion.
AB  - Folate plays a critical role in maintaining normal metabolic, energy,
      differentiation and growth status of all mammalian cells. The disturbances in
      body folate homeostasis such as intestinal malabsorption in alcoholism are well
      known contributor to folate deficiency associated disorders. The study was sought
      to delineate the kinetic features of folate transport in intestinal absorptive
      epithelium that could highlight insights of malabsorption during alcoholism. We
      studied [(3)H]-folic acid transport in intestinal brush border membrane (BBM)
      after 3 months of ethanol administration at 1 g/kg body weight/day to rats. The
      results showed that the folate transport exhibited saturable kinetics and was pH,
      Na(+), temperature, divalent cation sensitive, besides -SH group(s) was/were
      found important in the folate transport system to be efficiently operative.
      Importantly, the decreased intestinal BBM folate transport in chronic alcoholism
      was associated with increased K (m) and decreased V (max) during alcoholism. In
      addition, S-S group status of the transporter and presence of Na(+ )at the
      absorptive site seems to be perturbed during ethanol ingestion. However,
      H(+)/folate(-) coupled transport provided the driving force for transport as pH
      optimum in acidic range was not altered during alcoholism. The inhibition
      constants of methotrexate and unlabelled folic acid revealed that the two
      analogues are handled differently by the folate transport system. In addition,
      the low activity of folate transport system during chronic ethanol exposure was
      associated with low RBC folate levels. Overall, these findings suggest that the
      deregulated folate transport kinetics might contribute to intestinal folate
      malabsorption in alcoholism.

PMID- 17530185
TI  - Gender related differential effects of Omega-3E treatment on diabetes-induced
      left ventricular dysfunction.
AB  - The present study was designed to determine whether there are beneficial effects
      of intake of Omega-3E (containing 70% pure omega-3 and 2% natural vitamin E) in
      cardiac dysfunction of diabetic rats. We also examined whether there are gender
      related differences in the responses to the intake of Omega-3E on the heart
      dysfunction. Experiments were performed by using Langendorff-perfused hearts from
      normal, diabetic (with 50 mg/kg streptozotocin), and Omega-3E (50 mg/kg body
      weight/day) treated diabetic 3-month-old Wistar rats. Omega-3E treatment of the
      diabetics caused small, but significant decrease (13% and 14% female versus male)
      in the blood glucose level. Omega-3E treatment of the diabetic female rats did
      not prevent diabetes-induced decrease in left ventricular developed pressure
      (LVDP) and increase in left ventricular end-diastolic pressure (LVEDP) with
      respect to the control female rats. On the other hand, the treatment of diabetic
      male rats caused significant recovery in depressed LVDP. Furthermore, such
      treatment of diabetic female and male rats caused significant recovery in
      depressed rates of changes of developed pressure. This effect was more
      significant in males. Besides, Omega-3E caused significant further lengthening in
      the diabetes-induced increased time to the peak of the developed pressure in
      females, while it normalized the lengthening in the relaxation of the developed
      pressure in diabetic males. In addition, Omega-3E treatment caused significant
      restorations in the diabetes-induced altered activities of antioxidant enzymes
      without any significant gender discrepancy. Present data show that there are
      gender related differences in diabetic heart dysfunction and the response to
      antioxidant treatment.

PMID- 17530186
TI  - Cloning and promoter activity of rat Smad1 5'-flanking region in rat hepatic
      stellate cells.
AB  - Smad1 is an important signaling molecule for members of transforming growth
      factor-beta (TGF-beta) superfamily. Increased expression of Smad1 in activated
      hepatic stellate cells (HSCs) indicates a role of Smad1 in liver fibrosis.
      Therefore, understanding of Smad1 gene expression could be important to control
      the activation of HSCs. Current study reports the cloning and characterizing rat
      Smad1 5'-flanking region in liver cells. Rat Smad1 5'-flanking region was cloned
      by PCR method. Promoter deletional analysis and electrophoretic mobility shift
      assay (EMSA) were examined in hepatocyte and HSCs cell line (CFSC-8B cells),
      respectively. Results indicated that rat Smad1 used GC-box as its promoter and
      there was a transcriptional regulatory element located at the region of -163 to 
      56bp. EMSA demonstrated two bands on Smad1 promoter region. Smad1 promoter
      activity was higher in CFSC-8B cells cultured on uncoated plastic dish than that
      of CFSC-8B cells cultured on Matrigel-coated plastic dish. In conclusion, rat
      Smad1 promoter was cloned and characterized in hepatocyte and HSC cell line (CFSC
      8B cells) at different culture conditions.

PMID- 17530187
TI  - The over-expression of p53 H179Y residue mutation causes the increase of cyclin
      A1 and Cdk4 expression in HELF cells.
AB  - Down-regulation of p53 expression has been found in a broad range of human
      cancers and cell proliferation disorders, indicating that p53 plays a key role in
      cell cycle regulation and tumor suppression. In our current study, we transfected
      human embryonic lung fibroblast (HELF) cells with pcDNA3-wild-type p53 (pcDNA3
      wtp53) plasmid, or pcDNA3-H179Y-mutated p53 (pcDNA3-mtp53) plasmid that mimics
      the mutation found in some human lung tumors, and further studied the role of p53
      in the regulation of cell proliferation. Over expression of wild-type p53 caused
      cell cycle arrest at G1 phase with reduced cell size, decreased expression of
      cyclin D3, cyclin E, Cdk2 and Cdk4, and increased expression of p21. In contrast,
      over expression of H179Y-mutant p53 promoted G1 to S phase transition with
      enlarged cell size and increased cyclin A1 and Cdk4 expression in HELF cells.
      These results indicate that mutation at the p53 H179Y residue up-regulates cyclin
      A1 and Cdk4 expression, and promotes HELF cell proliferation.

PMID- 17530188
TI  - Decreased dopamine D(2) receptor function in cerebral cortex and brain stem:
      their role in hepatic ALDH regulation in ethanol treated rats.
AB  - Ethanol exerts numerous pharmacological effects through its interaction with
      various neurotransmitters. The dopaminergic pathway is associated with cognitive,
      endocrine, and motor functions, and reinforcement of addictive substances or
      behaviours. Aldehyde dehydrogenase (ALDH) is a vital enzyme involved with alcohol
      metabolism and detoxification. In the present study, we investigated the role of
      cerebral cortex and brain stem dopamine D(2) receptors in the functional
      regulation on ALDH enzyme activity, in ethanol administrated rats. Two groups of
      rats were selected viz. control and alcoholic. Cerebral cortex, brain stem and
      the liver dopamine content was decreased significantly (P < 0.05, 0.05, 0.001,
      respectively) and homovanillic acid/dopamine (HVA/DA) ratio has significantly
      increased (P < 0.05, 0.001 and 0.001), respectively in ethanol treated rats when
      compared to control. Scatchard analysis of [(3)H]YM-09151-2 binding to synaptic
      membrane preparations of cerebral cortex and brain stem showed a significant
      decrease (P < 0.001, 0.05, respectively) in B (max) in ethanol treated rats
      compared to control and the K (d) also decreased significantly (P < 0.05). The
      ALDH analysis showed a significant increase (P < 0.05) in V (max) in cerebral
      cortex, plasma and liver of experimental rats when compared with control without
      having significant change in brain stem but with decreased K (m) (P < 0.001). Our
      results suggest that decreased function of dopamine mediated through DA D(2)
      receptor in the cerebral cortex and brain stem enhanced the brain, plasma and
      liver ALDH activity in ethanol treated rats. This ALDH regulation has
      significance to correct alcoholics from addiction due to allergic reaction
      observed in aldehyde accumulation.

PMID- 17530189
TI  - Proteomic identification of differently expressed proteins responsible for
      osteoblast differentiation from human mesenchymal stem cells.
AB  - Human mesenchymal stem cells (hMSC) are a population of multipotent cells that
      can differentiate into osteoblasts, chondrocytes, adipocytes, and other cells.
      The exact mechanism governing the differentiation of hMSC into osteoblasts
      remains largely unknown. Here, we analyzed protein expression profiles of
      undifferentiated as well as osteogenic induced hMSC using 2-D gel electrophoresis
      (2-DE), mass spectrometry (MS), and peptide mass fingerprinting (PMF) to
      investigate the early gene expression in osteoblast differentiation. We have
      generated proteome maps of undifferentiated hMSC and osteogenic induced hMSC on
      day 3 and day 7. 2-DE revealed 102 spots with at least 2.0-fold changes in
      expression and 52 differently expressed proteins were successfully identified by
      MALDI-TOF-MS. These proteins were classified into 7 functional categories:
      metabolism, signal transduction, transcription, calcium-binding protein, protein
      degradation, protein folding and others. The expression of some identified
      proteins was confirmed by further RT-PCR analyses. This study clarifies the
      global proteome during osteoblast differentiation. Our results will play an
      important role in better elucidating the underlying molecular mechanism in hMSC
      differentiation into osteoblasts.

PMID- 17530190
TI  - Protein kinase catalytic subunit (PKAcat) from bovine lens: purification,
      characterization and phosphorylation of lens crystallins.
AB  - The purification and functional characterization of protein kinase A catalytic
      subunit (PKAcat) from bovine lens cytosol has been described. Purification to
      homogeneity has been achieved by using 100 kDa cut-off membrane filtration
      followed by Sephacryl S-300 chromatography and finally fractionating on High Q
      anion exchange column. The purified protein migrates as a single band of
      molecular mass approximately 41 kDa on 12.5% SDS-PAGE. Proteomic data from ion
      trap LC-MS when analyzed through NCBI blast program reveals significant homology
      (52%) with bovine zeta-crystallin and also some homology with pig casein kinase I
      alpha chain (38%) and SLA-DR1 beta 1 domain (38%). The search does not indicate
      homology with any known catalytic subunit of PKA. Inspite of the significant
      homology with the zeta-crystallin, our protein is different from it in terms of
      molecular mass. pI value of the kinase (5.3) obtained from 2D analysis is also
      different from zeta-crystallin (8.5). The protein is found to contain 17% alpha
      helix, 26.5% beta-sheet, 21.4% turn and 34.7% random coil. The active catalytic
      subunit of the bovine lens cAMP-dependent kinase belongs to Type I Calpha
      subtype. The enzyme shows maximum activity at 30 min incubation in presence of 5
      mM MgCl(2 )and 50 microM ATP. The kinase shows broad substrate specificity. It
      prefers Ser over Thr as phosphorylating residue. Phosphorylation of crystallin
      proteins, major protein fraction of bovine lens and phosphorylation of chaperone
      protein alpha crystallin by the kinase suggests that the kinase plays some
      crucial role in regulation of chaperone function within lens.

PMID- 17530191
TI  - Attenuated Leishmanial sphingolipid induces apoptosis in A375 human melanoma cell
      via both caspase-dependent and -independent pathways.
AB  - A fraction of attenuated Leishmanial lipid (ALL) rich in sphingolipids,
      previously shown to have apoptosis inducing activity in mouse melanoma (B16F10)
      and human melanoma (A375) cells, was resolved to isolate the bioactive
      sphingolipid. The mechanism of apoptosis induction by this bioactive attenuated
      Leishmanial sphingolipid (ALSL) was studied in A375 cells. Apoptosis induced by
      ALSL in A375 cells was found to be dose and time-dependent. Exposure of cells to
      ALSL resulted in a rapid increase in reactive oxygen species generation.
      Pretreatment of cells with the antioxidant N-acetyl-cystein reduced ROS
      generation and attenuated apoptosis induced by ALSL. Again, ALSL sensitization
      resulted in the activation of caspase-3 and -9 but not caspase-8. However,
      inhibitors of these caspases could not protect the cells completely from ALSL
      induced apoptosis. N-acetyl-cystein pretreatment was again found to attenuate the
      activation of caspase-3 and -9. ALSL treatment also resulted in the alteration of
      mitochondrial membrane potential, and release of pro-apoptotic factors such as
      cytochrome c and apoptosis inducing factor (AIF) from mitochondria. Furthermore,
      c-Jun N-terminal kinase was activated that resulted in apoptosis of A375 cells,
      whereas p38 MAPK was activated to counteract the stress generated in cells in
      response to ALSL treatment. Taken together, our results indicate that ALSL
      induced apoptosis of A375 cells is mediated by both mitochondrial caspase
      dependent and -independent pathways and it involves ROS and JNK activation in the
      mitogen-activated protein kinase cascade.

PMID- 17530192
TI  - Zinc mediated normalization of histoarchitecture and antioxidant status offers
      protection against initiation of experimental carcinogenesis.
AB  - The present study evaluated the inhibitory effects of zinc on colonic antioxidant
      defense system and histoarchitecture during 1,2 dimethylhydrazine (DMH) induced
      colon carcinogenesis in male Spraque Dawley rats. The rats were segregated into
      four groups viz., normal control, DMH treated, zinc treated, DMH + zinc treated.
      Colon carcinogenesis was induced through weekly subcutaneous injections of DMH
      (30 mg/kg body weight) for 8 weeks. Zinc (in the form of zinc sulphate) was
      supplemented to rats at a dose level of 227 mg/l in drinking water, ad libitum
      for the entire duration of the study. Increased lipid peroxidation was
      accompanied by a decrease in reduced glutathione (GSH), glutathione reductase
      (GR), glutathione-s-transferase (GST), superoxide dismutase (SOD), and catalase.
      Administration of zinc to DMH treated rats significantly decreased the lipid
      peroxidation levels with simultaneous enhancement of GSH, GR, GST, SOD, and
      Catalase. Histopathological studies from DMH treated rats revealed
      disorganization of colonic histoarchitecture. However, zinc treatment to DMH
      treated rats greatly restored normalcy in the colonic histoarchitecture, with no
      apparent signs of abnormality. Energy Dispersive X-Ray Fluorescence (EDXRF)
      studies revealed a significant decrease in tissue concentrations of zinc in the
      colon following DMH treatment, which upon zinc supplementation were recovered to
      near normal levels. In conclusion, the results of this study suggest that zinc
      has a beneficial effect during the initiation of key events leading to the
      development of experimentally induced carcinogenesis.

PMID- 17530193
TI  - Effect of recombinant Mce4A protein of Mycobacterium bovis on expression of TNF
      alpha, iNOS, IL-6, and IL-12 in bovine alveolar macrophages.
AB  - The pathogenesis of tuberculosis-causing Mycobacterium bovis is largely due to
      its ability to enter and survive in alveolar macrophages. Its mechanism of entry,
      mediated by proteins encoded by mammalian cell entry (mce) genes, is important
      for its pathogenesis. Here we focussed on the role of the Mce4A protein in the
      pathogenesis of M. bovis in cattle. Cell livability decreased in a dosage
      dependent manner when Mce4A proteins were used to stimulate alveolar macrophages,
      which suggested that the recombinant Mce4A protein significantly inhibited
      alveolar macrophage activity. To test whether Mce4A modulates the gene expression
      profile of alveolar macrophages, alveolar macrophages were stimulated by Mce4A
      protein and other proteins/ligands (such as MtbPPD, MbPPD, and BCG), followed by
      real-time RT-PCR assay for the mRNA expression level of TNF-alpha, iNOS, IL-6,
      and IL-12. The results showed that the expression of TNF-alpha, iNOS, and IL-6 in
      alveolar macrophages was up-regulated by stimulation with the recombinant Mce4A
      protein of M. bovis; in contrast, expression of IL-12 was unaffected. MbPPD and
      BCG up-regulated the mRNA expression of TNF-alpha, iNOS, IL-6, and IL-12 (P <
      0.05), whereas MtbPPD stimulated the mRNA expression of TNF-alpha, IL-6, and IL
      12 with no effect on iNOS. This study suggests that Mce4A proteins may induce the
      body's inflammation response to M. bovis and therefore may play an important role
      in the immune response.

PMID- 17530194
TI  - [Arthroscopic treatment of posterior shoulder instability].
AB  - OBJECTIVE: Reconstruction of the posterior stabilizing structures of the
      glenohumeral joint in arthroscopic technique. INDICATIONS: Posterior shoulder
      instability and/or chronic subluxations with lesions of the posterior labrum and
      capsuloligamentous structures. CONTRAINDICATIONS: Voluntary instability or
      posterior instability due to pathologic muscle patterning, posterior instability
      with glenoid fracture, large bone defects of the humeral head (20% of the
      inferior posterior glenoid) or locked posterior dislocations, dysplasia of the
      glenoid with pathologic retroversion > 25 degrees . SURGICAL TECHNIQUE:
      Mobilization of the pathologic and extraanatomically healed labroligamentous
      complex, decortication of the glenoid rim, repositioning and refixation of the
      labroligamentous complex at the glenoid rim using suture anchors. POSTOPERATIVE
      MANAGEMENT: Abduction splint at 15 degrees for 3 weeks. Functional therapy with
      passive mobilization that avoids forced internal rotation. Muscle strengthening
      only after free range of motion has been achieved. Return to sports that put
      strain on the shoulder after 6 months. RESULTS: Eleven patients with a mean age
      of 31 years were prospectively documented and followed for a mean of 33 months
      postoperatively. One patient suffered from a traumatic recurrence and one patient
      experienced recurrent subluxations. The overall mean Rowe score was 95 out of 100
      points.

PMID- 17530195
TI  - [Arthroscopic stabilization of the shoulder with suture anchors with special
      reference to the deep anterior-inferior portal (5.30 o'clock)].
AB  - OBJECTIVE: Arthroscopic (re)stabilization of the unstable shoulder by anatomic
      refixation of the detached capsulolabral complex with suture anchors or reduction
      of excessive capsule volume by capsule plication. INDICATIONS: Any type of
      shoulder instability (anterior, posterior, inferior, or multidirectional
      instability). Revision stabilization (even after primary open stabilization).
      Bone defects affecting < 25% of the glenoid surface. Lesions of the superior
      biceps tendon anchor complex (SLAP lesion). CONTRAINDICATIONS: Preexisting bone
      defects of the glenoid affecting > 25% of the glenoid surface. "Engaging" Hill
      Sachs defects: osseous defects of the humeral head that engage with the anterior
      glenoid rim in extreme external rotation/abduction and consequently lead to
      shoulder dislocation. Bone-related etiology, e. g., clearly increased glenoid
      retroversion/anteversion or glenoid dysplasias (e. g., inverse pear shape).
      Voluntary shoulder dislocation in young patients until the end of the growth
      period. SURGICAL TECHNIQUE: Diagnostic arthroscopy and additional procedures
      based on clinical and intraoperative findings. For anterior-inferior instability,
      an anterior-superior approach is made with mobilization of the labrum and
      decortication of the glenoid. Creation of deep anterior-inferior portal and
      insertion of the anchors in 5.30, 4.30 and 3.00 o'clock position. The sutures are
      pulled through the capsulolabral complex and tied arthroscopically.
      Reconstruction of the inferior glenohumeral ligament is especially important.
      Lesions of the superior biceps tendon anchor and/or posterior labrum detachment
      can be treated by the same technique. Capsule plication with PDS sutures can be
      performed to decrease a large rotator interval or excessive capsule volume. The
      range of motion at the shoulder is limited for 6 weeks postoperatively (depending
      on the initial direction of the instability). RESULTS: At the authors' hospital
      over 600 arthroscopic shoulder stabilizations using the deep anterior-inferior
      portal have been completed so far. The redislocation rate for the first 147
      patients (average follow-up of 3 years) treated with the technique described here
      is 6.1% and is slightly higher for arthroscopic revision stabilizations (n=43; of
      these, redislocation n=3 and reinstability n=3). There were no instances of
      axillary nerve lesion.

PMID- 17530196
TI  - [Open reduction and internal fixation by primary subtalar arthrodesis for
      intraarticular calcaneal fractures].
AB  - OBJECTIVE: To prevent the development of painful posttraumatic degenerative joint
      disease by a primary one-stage procedure to treat calcaneal fractures involving
      obvious comminution or severe and extensive cartilage damage to the subtalar
      facet. INDICATIONS: Sanders type IV calcaneal fractures with severe and extensive
      cartilage destruction. The definitive indication for arthrodesis can only be
      established intraoperatively. CONTRAINDICATIONS: Severe closed IIIrd or IV nd
      degree soft-tissue injury according to Tscherne & Oestern. Open fractures.
      Vascular impairment. Diabetes mellitus. Generalized or local inactivity
      osteoporosis > grade I according to Kanis. Age > approximately 50 years. SURGICAL
      TECHNIQUE: Extended lateral approach. Osteosynthesis of the calcaneal fracture,
      reconstruction of axes, subtalar facet denuded of cartilage, bone graft from the
      anterior iliac crest, arthrodesis by screw fixation of the subtalar joint.
      POSTOPERATIVE MANAGEMENT: After edema has subsided, mobilization without a cast
      and partial loading up to 15 kg for 12 weeks. Clinical and radiologic review
      after 6 and 12 weeks. RESULTS: This operation is performed very rarely. Within a
      retrospective study including patients over a period of 14 years (1990-2004), a
      total of 434 patients with a calcaneal fracture were treated surgically. Primary
      subtalar arthrodesis was performed in only six of these patients. Healing within
      4 months was achieved in all six patients. The clinical and radiologic follow-ups
      took place on average after 4.9 years (2.5-7.5 years). Radiologically, almost
      anatomic reconstruction of the axes could be achieved (Gissane and Bohler angles,
      talometatarsal and talocalcaneal angles, calcaneal length and width). The
      functional outcomes were also good to very good with an average AOFAS (American
      Orthopaedic Foot and Ankle Society) Score of 88 points (63-94 points) and a
      Hanover Score of 84 points (62-90 points).

PMID- 17530197
TI  - [Open posterior-inferior capsule shift for the treatment of atraumatic posterior
      shoulder instability].
AB  - OBJECTIVE: Restoration of functional stability and full range of shoulder
      mobility. INDICATIONS: Atraumatic, recurrent posterior dislocation or subluxation
      in cases of excessive posterior joint capsular volume without clinically relevant
      destruction of the glenoid or dysplasia. Additional procedure for traumatic
      posterior instability after reattachment of the labrum or screw fixation of the
      posterior glenoid fragment. CONTRAINDICATIONS: Capsular shift should not be an
      isolated procedure in glenoid hypoplasia and/or glenoid retroversion > 15 degrees
      (relative). Multidirectional instability (relative). Deliberate (psychogenic)
      posterior instability (relative). SURGICAL TECHNIQUE: Lateral decubitus position,
      Rockwood approach. Dissection of the posterior joint capsule after split of the
      external rotator muscles between the infraspinatus and teres minor. T-shaped
      incision of the posterior capsule with a medial base of about 0.5-1 cm lateral to
      the posterior glenoid rim. Retraction of the caudal and cranial capsular flaps.
      Inspection of the posterior labrum. If the labrum is detached, anatomic
      refixation of the labrum with suture anchors. The caudal flap is shifted
      cranially and medially in adduction and about 20 degrees external rotation. The
      cranial flap is then shifted caudally and medially. Suture with close-meshed
      Vicryl sutures. This creates double-contouring centrally and plication of the
      posterior capsule with reduction of the pathologically increased capsule volume.
      After wound closure and sterile dressing, the preoperatively prepared
      antirotation cast is applied and should be worn for 6 weeks. RESULTS: From
      10/2002 to 09/2004, eight patients with atraumatic, isolated posterior shoulder
      instability were treated using the technique described above. All patients were
      available to follow-up 2 years after the operation. There were no perioperative
      complications and no neurologic deficits related to surgery. All patients
      achieved freedom of movement at the shoulder joint. In two patients, recurrent
      posterior dislocation occurred after the 7th and 23rd postoperative month.

PMID- 17530198
TI  - [Revision of failed fracture hemiarthroplasties to reverse total shoulder
      prosthesis through the transhumeral approach : method incorporating a pectoralis
      major-pedicled bone window].
AB  - OBJECTIVE: Alleviation of pain, restoration of function and active range of
      motion. INDICATIONS: Failed posttraumatic shoulder prostheses with insufficient
      rotator cuff, pseudoparalysis, chronic instability, severe ankylosis.
      CONTRAINDICATIONS: Advanced glenoid destruction. Severe lesions of the deltoid
      muscle (> 50%) and axillary nerve palsy. Florid infections. SURGICAL TECHNIQUE:
      Deltopectoral approach. Exposure of the failed implant and explantation by
      fenestration of the humerus. Periarticular release with preservation of
      neurovascular structures. Exposure of the glenoid, cementless fixation of the
      glenoid base plate (metaglene) and application of the glenoid ball (glenosphere).
      Fenestration of the humeral shaft, removal of bone cement, placement of wire and
      suture loops, and cemented implantation of the humeral component (long revision
      stem) in 10-30 degrees retroversion related to the long axis of the forearm.
      Anatomic reconstruction of the soft tissues with preservation of the external
      rotators (reattachment of dislocated tubercles and, if necessary, transposition
      of latissimus dorsi and teres major as described by L'Episcopo). POSTOPERATIVE
      MANAGEMENT: For 6 weeks postoperatively, abduction brace and passive or active
      assisted exercises including continuous passive motion (Ormed, Freiburg,
      Germany). RESULTS: From 2000 to 2005, a total of 84 shoulder replacement
      revisions were performed with the reverse prosthesis, of which 34 were revisions
      of failed fracture hemiarthroplasties (five men, 29 women) through a bone window
      in the humerus. 25 patients were followed prospectively for up to 59 months
      postoperatively; an additional nine patients were interviewed by telephone or in
      writing (n=34, average age 68 years [59-82 years], average follow-up 31.5 months
      [12-59 months]). The preoperative age- and gender-related Constant Score was
      17.5% and improved to 63% postoperatively. Range of motion for active elevation
      and internal rotation was substantially improved (average elevation
      preoperatively 48 degrees , postoperatively 125 degrees ). Pain was relieved in
      every patient. Function correlated to the extent of soft-tissue damage. 14
      patients were very satisfied with the surgical outcome, 16 were satisfied and
      four dissatisfied. There were eight complications in total.

PMID- 17530199
TI  - [Implantation of the ProDisc intervertebral disk prosthesis for the lumbar
      spine].
AB  - OBJECTIVE: To eradicate treatment-resistant lower back pain caused by painful
      degeneration of the intervertebral disks. To avoid the disadvantages of
      alternative fusion surgery, especially degenerative wear and tear on adjacent
      segments, by maintaining the mobility of the affected motion segments.
      INDICATIONS: Treatment-resistant lower back pain due to painful degeneration of
      the intervertebral disks ("degenerative disk disease"). CONTRAINDICATIONS:
      Spondylolisthesis, scoliosis, osteoporosis, infection, spinal stenosis,
      degeneration of the vertebral articulations. SURGICAL TECHNIQUE: The
      intervertebral disk is excised through an anterior approach. It is essential to
      retain good mobility of the motion segment, if necessary, by resection of the
      posterior longitudinal ligament. After revitalization of the vertebral base and
      cover plates and chiseling of a groove for the keel of the prosthesis, the upper
      and lower prosthetic plates are inserted and the polyethylene inlay is locked
      into place. RESULTS: From April 2002 to May 2004, 36 ProDisc (Synthes Spine, West
      Chester, PA, USA) modular intervertebral disk prostheses were implanted in 34
      patients (26 women, eight men, average age 44.3 years). Clinical evaluation was
      based on the visual analog scale (VAS), the Oswestry Disability Index (ODI), and
      the SF-36 Questionnaire. Follow-up assessment also included radiographic views of
      the lumbar spine in two planes in flexion and extension and standing. The follow
      up interval for all patients was at least 1 year and 2 years for 14 patients. 26
      patients were very satisfied with the operation, five patients were satisfied,
      and three patients were less satisfied. The clinical parameters recorded on the
      VAS, ODI and SF-36 improved from 7.4 to 2.8 (VAS), 48.0 to 13.1 (ODI) and 31.3 to
      44.2 (SF-36, Physical Component Summary Score) from the time of the preoperative
      assessment to the 1-year follow-up. The range of motion at the segment with the
      implanted prosthesis was 10 degrees on average at L4/5 and 7 degrees on average
      at L5/S1 1 year postoperatively.

PMID- 17530200
TI  - Laser-induced pattern formation in liquid sulfur. An indication of laser-induced
      phase transition to ordered polymer.
AB  - Liquid sulfur is a well-known liquid which exhibits a polymerization transition
      at T(p)=159 degrees C. Recently, it was found from our experiments that such a
      transition can be induced below T(p) through laser illumination and that an
      iridescent pattern appears under strong illumination with a pulsed laser of more
      than 60 mJ/cm(2) pulse. It is proposed that the visible change in iridescence is
      due to a macroscopic reconstruction of laser-generated polymers and that a laser
      induced phase transition takes place from a freely expanded polymer phase to an
      ordered polymer phase when increasing the laser illumination. To further examine
      this possibility, the time variation of the iridescent pattern has been fully
      investigated using a macro lens, a polarized microscope and an optical
      microscope. In an analysis of the iridescent pattern, a rapid decrease in the
      area was observed after an initial slow decrease, suggesting a type of phase
      transition. Results from the observation of a quenched sulfur sample with a
      polarized microscope gave evidence that the iridescent region consists of
      polymers. Through observation of the liquid with a microscope, a striped pattern
      with micrometer sized spacing was noted in the iridescent pattern. A drastic
      color change was observed in the pattern from its generation to its
      disappearance. Sample thickness dependence of the pattern was also observed.
      These results were well explained by assuming the self-arrangement of laser
      generated colloidal polymers.

PMID- 17530201
TI  - Steady drainage in emulsions: corrections for surface Plateau borders and a model
      for high aqueous volume fraction.
AB  - We compare extensive experimental results for the gravity-driven steady drainage
      of oil-in-water emulsions with two theoretical predictions, both based on the
      assumption of Poiseuille flow. The first is from standard foam drainage theory,
      applicable at low aqueous volume fractions, for which a correction is derived to
      account for the effects of the confinement of the emulsion. The second arises
      from considering the permeability of a model porous medium consisting of solid
      sphere packings, applicable at higher aqueous volume fractions. We find
      quantitative agreement between experiment and the foam drainage theory at low
      aqueous volume fractions. At higher aqueous volume fractions, the reduced flow
      rate calculated from the permeability theory approaches the master curve of the
      experimental data. Our experimental data demonstrates the analogy between the
      problem of electrical flow and liquid flow through foams and emulsions.

PMID- 17530205
TI  - Substrate pretreatment: the key to effective enzymatic hydrolysis of
      lignocellulosics?
AB  - Although the structure and function of cellulase systems continue to be the
      subject of intense research, it is widely acknowledged that the rate and extent
      of the cellulolytic hydrolysis of lignocellulosic substrates is influenced not
      only by the effectiveness of the enzymes but also by the chemical, physical and
      morphological characteristics of the heterogeneous lignocellulosic substrates.
      Although strategies such as site-directed mutagenesis or directed evolution have
      been successfully employed to improve cellulase properties such as binding
      affinity, catalytic activity and thermostability, complementary goals that we and
      other groups have studied have been the determination of which substrate
      characteristics are responsible for limiting hydrolysis and the development of
      pretreatment methods that maximize substrate accessibility to the cellulase
      complex. Over the last few years we have looked at the various lignocellulosic
      substrate characteristics at the fiber, fibril and microfibril level that have
      been modified during pretreatment and subsequent hydrolysis. The initial
      characteristics of the woody biomass and the effect of subsequent pretreatment
      play a significant role on the development of substrate properties, which in turn
      govern the efficacy of enzymatic hydrolysis. Focusing particularly on steam
      pretreatment, this review examines the influence that pretreatment conditions
      have on substrate characteristics such as lignin and hemicellulose content,
      crystallinity, degree of polymerization and specific surface, and the resulting
      implications for effective hydrolysis by cellulases.

PMID- 17530206
TI  - [Central induction area. Reduction of non-operative time without additional
      costs].
AB  - BACKGROUND: Induction areas (IA) can lead to more efficient operating sessions
      through shortening the changeover time between patients. To date IAs have always
      required additional staff members, whose cost was only partly covered by
      improvements in productivity. The objective of this project was to demonstrate
      that a reduction in non-operative time through a newly introduced induction area
      can be achieved without a need for extra personnel. METHODS: Non-operative time
      in 5,963 ENT, orthopedic and cardiac surgical patients from 8 operating theatres
      were studied for 1 year before and 1 year after the introduction of an induction
      area. The non-operative time was defined as the time between the end of surgical
      procedures in one operation and the start of surgical procedures in the next,
      within regular working hours. Through reallocation of anesthetic nursing and
      medical staff it was possible to introduce the induction area without increasing
      staff numbers. RESULTS: Non-operative time was significantly reduced from 20 min
      (range 10-30 min) to 14 min (5-25 min). Subgroup analysis showed significant
      reductions in all specialities: from 10 min (2.5-20 min) to 5 min (0-20 min) in
      1,240 cardiac surgical patients, 25 min (20-35 min) to 15 min (5-25 min) in 2,433
      ENT patients and 20 min (10-30 min) to 10 min (0-20 min) in 2,290 orthopedic
      patients. There were no critical incidents attributable to patient handover.
      DISCUSSION AND CONCLUSIONS: An induction area can be established and can reduce
      non-operative time and improve operation theatre throughput without the need for
      extra personnel. The efficiency of these measures will be increased when the
      relevant surgical organizational measures are taken to adjust to the faster
      anesthesiology workflow. The induction area does not lead to a higher rate of
      critical incidents. To what extent the induction area can be used for structured
      training of doctors and nurses, remains to be investigated.

PMID- 17530207
TI  - [Pharmacokinetic-pharmacodynamic models for inhaled anaesthetics].
AB  - Pharmacokinetic models can be differentiated into two groups: physiological-based
      models and empirical models. Traditionally the pharmacokinetics of volatile
      anaesthetics are described using physiological-based models together with the
      respective tissue-blood distribution coefficients. The compartments of the
      empirical model have no anatomical equivalents and are merely the product of the
      mathematical procedure for parameter estimation. The end expiratory concentration
      of volatile anaesthetics is approximately equal to the arterial concentration
      and, therefore, the description of the transition between plasma and effect site
      for volatile anaesthetics plays a central role. The most important parameter here
      is the k(e0) value which is a time constant and describes the time delay for the
      transition from the central compartment to the calculated effect compartment. The
      k(e0) values for sevoflurane and isoflurane are the same but the concentration
      balance between the end-tidal concentration and the effect compartment occurs
      twice as quickly with desflurane. In clinical practice volatile anaesthetics are
      normally combined with N(2)O and/or opioids. This results in an additive
      interaction between volatile anaesthetics and N(2)O but a synergistic interaction
      of volatile anaesthetics with opioids. However, there are relatively few
      investigations on the interactions between the clinically widely used combination
      of volatile anaesthetics, N(2)O and opioids.

PMID- 17530208
TI  - Transcript profiles of dendritic cells of PLOSL patients link demyelinating CNS
      disorders with abnormalities in pathways of actin bundling and immune response.
AB  - Rare monogenic dementias have repeatedly exposed novel pathways guiding to
      details of the molecular pathogenesis behind this complex clinical phenotype. In
      this paper, we have studied polycystic lipomembranous osteodysplasia with
      sclerosing leukoencephalopathy (PLOSL), an early onset dementia with bone
      fractures caused by mutations in TYROBP (DAP12) and TREM2 genes, which encode
      important signaling molecules in human dendritic cells (DCs). To identify the
      pathways and biological processes associated with DAP12/TREM2-mediated signaling,
      we performed genome wide transcript analysis of in vitro differentiated DCs of
      PLOSL patients representing functional knockouts of either DAP12 or TREM2. Both
      DAP12- and TREM2-deficient cells differentiated into DCs and responded to
      pathogenic stimuli. However, the DCs showed morphological differences compared to
      control cells due to defects in the actin filaments. Not unexpectedly, transcript
      profiles of the patient DCs showed differential expression of genes involved in
      immune response. Importantly, significantly diverging transcript levels were also
      evident for genes earlier associated with other disorders of the central nervous
      system (CNS) and genes involved in the remodeling of bone, linking these two
      immunological genes with critical tissue phenotypes of patients. The data
      underline the functional diversity of the molecules of the innate immune system
      and implies their significant contribution also in demyelinating CNS disorders,
      including those resulting in dementia.

PMID- 17530209
TI  - Cranial pneumatization and auditory perceptions of the oviraptorid dinosaur
      Conchoraptor gracilis (Theropoda, Maniraptora) from the Late Cretaceous of
      Mongolia.
AB  - The distribution of air-filled structures in the craniofacial and neurocranial
      bones of the oviraptorid ZPAL MgD-I/95, discovered at the Hermiin Tsav locality,
      Mongolia, is restored. Based on the complete obliteration of most of the cranial
      sutures, the specimen is identified as an adult individual of Conchoraptor
      gracilis Barsbold 1986. Except for the orbitosphenoids and epipterygoids, the
      preserved bones of the neurocranium are hollow. Three types of tympanic recess
      are present in Conchoraptor, a characteristic shared with troodontids,
      dromaeosaurids, and avian theropods. The contralateral middle ear cavities are
      interconnected by the supraencephalic pathway that passes through the dorsal
      tympanic recesses, the posterodorsal prootic sinuses and the parietal sinus. The
      spatial arrangements of the middle ear cavity and a derived neurocranial
      pneumatic system in Conchoraptor indicate enhancements of acoustic perception in
      the lower-frequency registers and of auditory directionality. We further
      speculate that this improvement of binaural hearing could be explained as an
      adaptation required for accurate detection of prey and/or predators under
      conditions of low illumination. The other potentially pneumatic structures of the
      Conchoraptor cranium include (1) recessus-like irregularities on the dorsal
      surface of the nasal and frontal bones (a putative oviraptorid synapomorphy;
      pos); (2) a subotic recess; (3) a sub-condylar recess; and (4) a posterior
      condylar recess (pos).

PMID- 17530210
TI  - [Congenital hemiplegia. A disease with manifold problems].
AB  - Congenital hemiplegia, defined as unilateral motor disability, is the hemiplegic
      type of cerebral palsy. The prevalence of congenital hemiplegia is estimated to
      be about 0.41-0.79/1000 live births. We examined 223 children (122 boys and 101
      girls) suffering from congenital hemiplegia at the age of 3 months to 12 years.
      Mild hemiplegia was found in 31%, a moderate form in 48%, and a severe form in
      21%. The upper limb was affected in more than half of the patients, only the
      lower extremity in one third, and both upper and lower limbs in 20%.
      Electroencephalographic abnormalities were found in 75.8% of the patients. The
      most frequent type of epilepsy was complex partial seizures (33%). Severity of
      the motor handicap, grade of EEG abnormalities, and the prevalence of epilepsy
      showed a significant correlation. The magnitude of the lesions in neuroimaging
      directly correlated with these three clinical variables, particularly in children
      with cortical and subcortical defects (84.2%). Strabismus was the most common
      visual impairment (17%), while hearing impairment was found in 8% of the
      patients. Of them, 38.3% showed no cognitive deficits, while those with severe
      congenital hemiplegia were found to have a lower intelligence quotient.

PMID- 17530211
TI  - [Health and health care of migrants with particular regard to addiction].
AB  - Adequate knowledge about the target group is essential for user-focused health
      care. Little differentiated information on the health and health care of migrants
      is available in Germany, and focused research on migrant groups hardly exists.
      The burden of the migration itself, the change in the socioeconomic status
      (compared to the home country) and - compared with the locals - a more restricted
      access to the health care system affect the health of migrants. A major health
      problem with this group is addiction. Characteristics of health and health
      behaviour of Turkish- and Russian-speaking migrants in Germany are examined by a
      study supported by the German Federal Ministry of Education and Research.

PMID- 17530212
TI  - [MR spectroscopy in brain tumors].
AB  - MRT allows the anatomical visualization of intracerebral space-occupying lesions,
      and when magnetic resonance spectroscopy (MRS) is used in routine clinical
      practice it can give more information and be helpful in the diagnosis of such
      lesions. In MRS with long echo times for nerve tissue there are five metabolites
      that are particularly significant: N-acetyl aspartate (NAA), creatine, choline,
      lactate, and lipids. NAA levels are lowered in the presence of intracerebral
      tumors. Creatine is lowered in situations of hypermetabolic metabolism and
      elevated in hypometabolic conditions, but remains constant in many pathologic
      states and can be used as a reliable reference value. With malignant tumors there
      are usually elevated choline concentrations, reflecting increased membrane
      synthesis and a higher cell turnover. The lactate level rises following a switch
      in metabolism from aerobic to anaerobic glycolysis, and this is frequently
      observed in the presence of malignant tumors. The occurrence of lipid peaks in a
      tumor spectrum suggests the presence of tissue necroses or metastases. There are
      typical constellations that are seen on MRS for individual tumors, which are
      discussed in detail in the present paper.

PMID- 17530213
TI  - [Anatomy and normal variations of paranasal sinuses in radiological imaging].
AB  - CT and MRI are the radiological methods of choice in the diagnostics of diseases
      of the paranasal sinuses. Detailed anatomical knowledge is mandatory for correct
      image interpretation. Before endonasal surgery the individually variable anatomic
      situation has to be known. This article describes radiologically relevant
      anatomical structures and summarizes normal variations.

PMID- 17530214
TI  - [Surgical sperm retrieval].
AB  - The introduction of intracytoplasmic sperm injection (ICSI) into the catalogue of
      assisted reproductive technologies in the mid-nineties has, for the first time,
      offered men who suffer from severe disorders of spermatogenesis and azoospermia
      the possibility of fathering a child. Different surgical techniques can be used
      to extract spermatozoa from these men from either the epididymis and/or the
      testis for ICSI. Surgical sperm retrieval offers a treatment for both patients
      with testicular or obstructive azoospermia in cases where microsurgical
      refertilization is not an option or has already failed. Among surgical techniques
      that have been developed over the years, microsurgical epididymial sperm
      aspiration (MESA) and testicular sperm extraction (TESE) have become the most
      popular. By utilizing these techniques together with the cryopreservation of
      extracted spermatozoa, a single surgical intervention is able to provide
      spermatozoa for several ICSI attempts.

PMID- 17530215
TI  - [A multimodal and multidisciplinary postoperative pain management concept].
AB  - Under-treatment of acute postoperative pain can lead to chronic pain with
      neuronal plasticity and result in poor surgical outcomes. A multimodal approach
      is therefore necessary to reduce postoperative pain by combining various
      analgesics with a non-pharmacological strategy. The current use of multimodal
      approaches, even for the management of postoperative pain, can reduce the side
      effects of pharmaceutical therapy alone as well as reducing the length of
      hospital stay. Adequate pain control is an important prerequisite for the
      application of rehabilitation programmes and will thereby influence functional
      outcome. In addition, patient satisfaction, as a major benchmarking factor after
      surgical treatment, is significantly influenced by the quality of postoperative
      pain management.

PMID- 17530216
TI  - [Stage oriented surgical cartilage therapy. Current situation].
AB  - Chondral or osteochondral lesions are typical injuries in orthopaedics and
      traumatology. Since there is no regeneration of damaged articular cartilage,
      these lesions can lead to premature osteoarthritis. Therefore, an adequate
      therapy for these injuries is an important goal. Nowadays, common methods in
      cartilage therapy are procedures for the recruitment of mesenchymal stem cells:
      autologous osteochondral transplantation and autologous chondrocyte
      transplantation. Currently, autologous osteochondral transplantation is the only
      procedure that allows the replacement of the defect with hyaline cartilage.
      However, this procedure has the problem of donor-site morbidity and limited
      availability of transplants. Stem cell recruiting procedures and autologous
      chondrocyte transplantation normally achieve a regeneration of the defect with
      only fibrocartilage tissue, but both can achieve good medium-term clinical
      results. Each of these therapeutic principles has certain major indications. In
      order to select an adequate therapy, the classification of chondral or
      osteochondral lesion is needed. From a multiplicity of classification systems,
      those of the ICRS are of particular clinical relevance.

PMID- 17530217
TI  - Reliability of mini-bronchoalveolar lavage for the measurement of epithelial
      lining fluid concentrations of tobramycin in critically ill patients.
AB  - OBJECTIVE: To evaluate the reliability of mini-bronchoalveolar lavage (mini-BAL)
      for the measurement of tobramycin concentrations in epithelial lining fluid (ELF)
      in comparison with conventional bronchoscopic bronchoalveolar lavage (BAL).
      DESIGN: Prospective, open-label study. SETTING: An intensive care unit and
      research ward in a university hospital. PATIENTS: Twelve critically ill adult
      patients with ventilator-associated pneumonia (VAP). INTERVENTIONS: All subjects
      received intravenous infusions of tobramycin 7-10 mg/kg once daily. After 2 days
      of therapy, the steady-state serum and ELF concentrations (obtained from BAL and
      mini-BAL) of tobramycin were determined by means of high-performance liquid
      chromatography. MEASUREMENTS AND RESULTS: We observed poor penetration of
      tobramycin in ELF of approximately approximately 12% with ELF peak concentrations
      of approximately approximately 3 mg/l with both methods. Good agreement in Bland
      Altman analysis (mean +/- SD bias = 0.04 +/- 0.38 mg/l) was observed between the
      two methods of sampling. CONCLUSION: Our results suggest that tobramycin 7-10
      mg/kg once daily in critically ill patients with VAP might provide insufficient
      lung concentrations in the case of difficult-to-treat pathogens. Besides, mini
      BAL, which is simple, non-invasive and easily repeatable at the bedside, appears
      to be a reliable method for the measurement of antibiotic concentrations in ELF
      in comparison with bronchoscopic BAL in critically ill patients with VAP.

PMID- 17530218
TI  - The "open lung" compromise.

PMID- 17530219
TI  - Continuous terlipressin infusion in patients with septic shock: less may be best,
      and the earlier the better?

PMID- 17530220
TI  - Safety and efficacy of colistin compared with imipenem in the treatment of
      ventilator-associated pneumonia: a matched case-control study.
AB  - OBJECTIVE: Our study aimed to determine the efficacy and safety of colistin in
      the treatment of ventilator-associated pneumonia (VAP) caused by pan-drug
      resistant Pseudomonas aeruginosa or Acinetobacter baumanii. DESIGN: Pairwise,
      retrospective exposed-unexposed study. SETTING: Combined medical and surgical
      intensive care unit of Habib Bourguiba University Hospital (Sfax, Tunisia).
      PATIENTS: Sixty patients with VAP caused by pan-drug-resistant A. baumanii or P.
      aeruginosa matched to 60 controls with VAP caused by A. baumanii or P. aeruginosa
      susceptible to imipenem. All patients had normal renal function at the onset of
      antibiotic therapy. INTERVENTIONS: Case patients were treated by colistin
      intravenously and control patients were treated by imipenem intravenously.
      MEASUREMENTS AND RESULTS: Baseline characteristics were similar between the
      colistin and imipenem groups. The mean duration of antibiotic therapy for VAP was
      9.5+/-3.8 days (range 5-22 days) with colistin and 8.9+/-2.8 days (range 5-20
      days) with imipenem (p=0.32). A favorable clinical response to antibiotic therapy
      for VAP occurred in 45 patients (75%) in the colistin group and in 43 patients
      (71.7%) in the imipenem group (p=0.68). The time to resolution of infectious
      parameters after the initiation of antibiotic therapy was not statistically
      different between the two groups. During the antibiotic course, none of the
      patients in either group developed renal failure. CONCLUSIONS: We conclude that
      colistin can be a safe and effective option in the treatments of VAP caused by
      pan-drug-resistant P. aeruginosa or A. baumanii.

PMID- 17530221
TI  - Does subarachnoid haemorrhage affect the innate immune response?

PMID- 17530223
TI  - Introduction to alveolar liquid clearance during lung injury: a crucial function-
      long ignored.

PMID- 17530224
TI  - Can pulsed electromagnetic fields protect joint cartilage?

PMID- 17530222
TI  - Alveolar epithelium and Na,K-ATPase in acute lung injury.
AB  - Active transport of sodium across the alveolar epithelium, undertaken in part by
      the Na,K-adenosine triphosphatase (Na,K-ATPase), is critical for clearance of
      pulmonary edema fluid and thus the outcome of patients with acute lung injury.
      Acute lung injury results in disruption of the alveolar epithelial barrier and
      leads to impaired clearance of edema fluid and altered Na,K-ATPase function.
      There has been significant progress in the understanding of mechanisms regulating
      alveolar edema clearance and signaling pathways modulating Na,K-ATPase function
      during lung injury. The accompanying review by Morty et al. focuses on intact
      organ and animal models as well as clinical studies assessing alveolar fluid
      reabsorption in alveolar epithelial injury. Elucidation of the mechanisms
      underlying regulation of active Na+ transport, as well as the pathways by which
      the Na,K-ATPase regulates epithelial barrier function and edema clearance, are of
      significance to identify interventional targets to improve outcomes of patients
      with acute lung injury.

PMID- 17530225
TI  - Bilateral complete discoid medial meniscus: how many cases? Associated
      pathologies?

PMID- 17530226
TI  - Treatment of anterolateral impingements of the ankle joint by arthroscopy.
AB  - Impingement syndromes of the ankle joint are among the most common intraarticular
      ankle lesions. Soft tissue impingement lesions of the ankle usually occur as a
      result of synovial, or capsular irritation secondary to traumatic injuries,
      usually ankle sprains, leading to chronic ankle pain. The aim of this prospective
      study was to evaluate arthroscopic debridement of an anterolateral soft tissue
      impingement of the ankle. During the period between October 2000 and February
      2004, 23 patients with residual complaints after an ankle sprain were diagnosed
      as anterolateral impingement of the ankle, and were treated by arthroscopic
      debridement. At a minimum of 6 months follow up, patients were asked to complete
      an American orthopaedic foot and ankle society (AOFAS) ankle and hind foot score.
      The average follow-up was 25 months (range 12-38). The average pre-operative
      patient assessed AOFAS score was 34 (range 4-57). At the end of follow-up the
      mean AOFAS score was 89 (range 60-100). In terms of patient satisfaction 22
      patients said they would accept the same arthroscopic procedure again for the
      same complaints. At the end of follow-up, 7 patients had excellent results, and
      14 patients had good results while two patients had fair results. We believe that
      arthroscopic debridement of the anterolateral impingement soft tissues are a
      good, and effective method of treatment.

PMID- 17530227
TI  - Diversity and geographical distribution of rhizobia associated with Lespedeza
      spp. in temperate and subtropical regions of China.
AB  - Eighty-eight root-nodule isolates from Lespedeza spp. grown in temperate and
      subtropical regions of China were characterized by a polyphasic approach. Nine
      clusters were defined in numerical taxonomy and SDS-PAGE analysis of whole cell
      proteins. Based upon further characterizations of amplified 16S rDNA restriction
      analysis (ARDRA), PCR-based restriction fragment length polymorphism of ribosomal
      IGS, 16S rDNA sequence analysis and DNA-DNA hybridization, these isolates were
      identified as Bradyrhizobium japonicum, B. elkanii, B. yuanmingense,
      Mesorhizobium amorphae, M. huakuii, Sinorhizobium meliloti and three genomic
      species related to B. yuanmingense, Rhizobium gallicum and R. tropici. The
      Bradyrhizobium species and R. tropici-related rhizobia were mainly isolated from
      the subtropical region and the species of Mesorhizobium, S. meliloti and R.
      gallicum-related species were all isolated from the temperate region.
      Phylogenetic analyses of nifH and nodC indicated that the symbiotic genes of
      distinct rhizobial species associated with Lespedeza spp. might have different
      origins and there was no evidence for lateral gene transfer of symbiotic genes.
      The results obtained in the present study and in a previous report demonstrated
      that Lespedeza spp. are nodulated by rhizobia with diverse genomic backgrounds
      and these Lespedeza-nodulating rhizobia were not specific to the host species,
      but specific to their geographic origins.

PMID- 17530228
TI  - Isolation and structural analysis of bamylocin A, novel lipopeptide from Bacillus
      amyloliquefaciens LP03 having antagonistic and crude oil-emulsifying activity.
AB  - Bacillus amyloliquefaciens strain LP03 isolated from soil, produced an
      antagonistic compound that strongly inhibited the growth of plant-pathogenic
      fungi and a lipopeptide biosurfactant. Also, isolated strain LP03 had a marked
      crude oil-emulsifying activity as it developed a clear zone around the colony
      after incubation for 24 h at 37 degrees C. LP03 was identified as Bacillus
      amyloliquefaciens by analysis of partial 16 S rRNA gene and partial gyrA gene
      sequence. The lipopeptide was purified by acid precipitation of cell-free culture
      broth, extraction of the precipitates with methanol, silica gel column
      chromatography, and reverse-phase, high-pressure liquid chromatography. The
      purified biosurfactant was analyzed biochemical structure by matrix-assisted
      laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF) and
      electrospray ionization mass spectrometry/mass spectrometry (ESI-MS/MS). The
      masses of the two peaks were observed by HPLC chromatography. Their masses were
      determined to be 1,044 and 1,058 m/z with MALDI-TOF mass spectrometry. As
      constituents of the peptide and lipophilic part of the m/z 1,022.6, seven amino
      acids (Glu-Leu-Met-Leu-Pro-Leu-Leu) and beta-hydroxy-C13 fatty acid were
      determined by ESI-MS/MS. The lipopeptide of 1,022.6 Da differed from surfactins
      in the substitution of leucine, valine and aspartic acid in positions 3, 4, and 5
      by methionine, leucine, and proline, respectively. Novel lipopeptide was
      designated as bamylocin A.

PMID- 17530229
TI  - Development and evaluation of a candidate reference measurement procedure for the
      determination of testosterone in human serum using isotope dilution liquid
      chromatography/tandem mass spectrometry.
AB  - A candidate reference measurement procedure for total testosterone in human serum
      involving isotope dilution (ID) coupled with liquid chromatography/tandem mass
      spectrometry (LC/MS/MS) has been developed and critically evaluated. The
      endogenous testosterone and its internal standard (testosterone-d (3)) were
      extracted from the serum matrix using a combination of solid-phase extraction and
      liquid-liquid extraction prior to reversed-phase LC/MS/MS. Accuracy of the
      measurements was evaluated by a recovery study using testosterone-spiked serum.
      The recovery of the added testosterone ranged from 100.0 to 100.3%. This method
      was applied to the determination of testosterone in frozen serum samples from
      three individual donors (one female and two males) with the testosterone
      concentrations ranging from 0.3 to 8.5 ng g(-1). Repeatability with within-set
      coefficients of variation (CVs) from 0.1 to 1.0% and intermediate precision with
      between-set CVs from 0.1 to 0.5% for both female and male serum materials were
      demonstrated. Excellent linearity was obtained for all linear regression lines.
      The detection limit at a signal-to-noise ratio of approximately 3 was 2 pg of
      testosterone in serum. Structural analogs as well as testosterone metabolites
      were tested and found to not interfere with the measurement of testosterone. This
      well-characterized LC/MS/MS method for serum testosterone, which demonstrates
      good accuracy and precision, and low susceptibility to interferences, qualifies
      as a reference measurement procedure that can be used to provide an accuracy base
      to which routine methods for testosterone can be compared and that will serve as
      a standard of higher order for measurement traceability.

PMID- 17530230
TI  - Food allergen detection methods and the challenge to protect food-allergic
      consumers.
AB  - The detection of allergenic ingredients in food products has received increased
      attention from the food industry and legislative and regulatory agencies over
      recent years. This has resulted in the improvement of measures aimed at the
      protection of food-allergic consumers. The controlled production of food products
      and control activities executed by food inspection agencies rely on the
      availability of methods capable of detecting traces of allergenic ingredients.
      The development of such methods faces a multitude of analytical challenges. Those
      challenges will be identified and discussed in this review. Furthermore, future
      developments and trends in analytical methodology as applied to the detection of
      food allergens are reported.

PMID- 17530231
TI  - ESI-MS method for in vitro investigation of skin penetration by copper-amino acid
      complexes: from an emulsion through a model membrane.
AB  - Copper can be found in many cosmetic formulations, mainly as complexes with
      peptides, hydroxyacids or amino acids. The main reason that the usage of this
      element in this context is still increasing is its beneficial biochemical
      activity, although the mechanism that enables its complexes to permeate through
      skin barriers is largely unknown. The ability of copper complexes with amino
      acids to penetrate through the stratum corneum and participate in copper ion
      transport processes is key to their cosmetic and pharmaceutical activities. The
      penetration process was studied in vitro in a model system, a Franz diffusion
      cell with a liposome membrane, where a liquid crystalline system with
      physicochemical properties similar to those of the intercellular cement of
      stratum corneum was used to model the skin barrier. The influences of various
      ligands on the model membrane migration rate of copper ions was studied, and the
      results highlighted the crucial roles of metal ion complex structure and
      stability in this process.

PMID- 17530232
TI  - Fourier-transform infrared (FTIR) spectroscopy for monitoring and determining the
      degree of crystallisation of polyhydroxyalkanoates (PHAs).
AB  - FTIR spectroscopy has been used to monitor and determine the degree of
      crystallisation in a sample of polyhydroxybutyrate-co-14%valerate (PHB-co-14%HV).
      Time series spectra of solution-cast films of the polymer revealed spectral
      changes attributed to the onset of crystallisation. Curve fitting was used to
      obtain an absolute measure of crystallinity. Mean centred principal-component
      analysis (PCA) revealed that 99.9% of the spectral variance could be attributed
      to factor 1. The loadings plot for factor 1 contained features attributable to
      crystalline and amorphous phases. These features were opposite in sign,
      indicating that changes in the spectra with the onset of crystallisation are
      simultaneous and opposite in direction, i.e. as the crystalline band increases
      the amorphous band decreases. Cross-peaks in asynchronous 2D correlation maps
      indicate there are likely to be very minor components that are changing out of
      phase. The presence of these minor components is supported by examination of the
      loadings of higher factors in the PCA model. PCA has been shown to be suitable
      for determining the number of dynamic spectral features and has enabled relative
      and objective monitoring of crystallisation kinetics.

PMID- 17530233
TI  - Elevated haemoglobin levels in the motor cortex following 1 Hz transcranial
      magnetic stimulation: a preliminary study.
AB  - One hertz transcranial magnetic stimulation (TMS) over the motor cortex has been
      reported to increase activity in the motor cortex contralateral to stimulation,
      as evidenced by the elevated motor evoked potential on the corresponding hand
      muscle. Little research, however, has assessed concomitant changes in the
      haemoglobin level in the unstimulated motor cortex. An aim of this study was to
      measure the change of oxy- and deoxy-haemoglobin levels in the left motor cortex
      after 20 min of 1 Hz TMS over the right motor cortex. Subjects carried out a
      finger to thumb tapping task sequentially with six blocks of ten cycles (30 s on
      and 60 s off). One block was performed before TMS and five after TMS. The results
      show that the level of oxyhaemoglobin in the unstimulated cortex increased after
      TMS over the contralateral hemisphere and that the increase lasted 40 min after 1
      Hz stimulation. Deoxy-haemoglobin was slightly decreased during the first 15 min
      after stimulation. The results identify long term physiological changes resulting
      from 1 Hz stimulation and help to inform our understanding of interhemispheric
      interactions in TMS studies.

PMID- 17530234
TI  - On rhythmic and discrete movements: reflections, definitions and implications for
      motor control.
AB  - At present, rhythmic and discrete movements are investigated by largely distinct
      research communities using different experimental paradigms and theoretical
      constructs. As these two classes of movements are tightly interlinked in everyday
      behavior, a common theoretical foundation spanning across these two types of
      movements would be valuable. Furthermore, it has been argued that these two
      movement types may constitute primitives for more complex behavior. The goal of
      this paper is to develop a rigorous taxonomic foundation that not only permits
      better communication between different research communities, but also helps in
      defining movement types in experimental design and thereby clarifies fundamental
      questions about primitives in motor control. We propose formal definitions for
      discrete and rhythmic movements, analyze some of their variants, and discuss the
      application of a smoothness measure to both types that enables quantification of
      discreteness and rhythmicity. Central to the definition of discrete movement is
      their separation by postures. Based on this intuitive definition, certain
      variants of rhythmic movement are indistinguishable from a sequence of discrete
      movements, reflecting an ongoing debate in the motor neuroscience literature.
      Conversely, there exist rhythmic movements that cannot be composed of a sequence
      of discrete movements. As such, this taxonomy may provide a language for studying
      more complex behaviors in a principled fashion.

PMID- 17530235
TI  - Tacrolimus severe overdosage after intake of masked grapefruit in orange
      marmalade.

PMID- 17530236
TI  - Haematological anticancer drugs in Europe: any added value at the time of
      approval?
AB  - OBJECTIVE: Current European regulations only require drugs to be safe and
      effective, although there is heavy demand for comparative efficacy data to
      demonstrate the added value of new drugs. The objective of the analysis reported
      here was to assess the added value of new anticancer drugs for haematological
      malignancies that have been approved by the European Medicines Agency (EMEA)
      based on the clinical data provided at the time of submission. METHODS:
      Information on the evidence supporting the approval was extracted from the
      European Public Assessment Reports (EPARs). Documents were surveyed for new
      applications and for subsequent extensions between January 1995, when the EMEA
      was set up, and May 2006. The added value of newly approved drugs was assessed by
      an algorithm that evaluates the strength of evidence based on methodological
      appropriateness (randomised comparison) and the importance of clinical advantage
      (in terms of the magnitude of benefit, hardness of outcome measures, adequacy of
      comparator). RESULTS: Eleven anticancer drugs were analysed. Of 17 indications,
      nine (53%) were approved on the basis of single-arm trials (SATs), and eight
      (47%) were approved on the basis of randomised controlled (clinical) trials
      (RCTs). The most frequently used endpoint was response rate (12 of 17
      indications, 70%). On the basis of our criteria, only four of the 11 drugs show a
      consistent added value. CONCLUSION: We were unable to establish an added value
      for about two thirds of the drugs evaluated in this study, primarily due to
      methodological aspects related to study design and endpoint robustness.

PMID- 17530237
TI  - Perfusion-sensitive MRI of pilocytic astrocytomas: initial results.
AB  - PURPOSE: To present the imaging and perfusion data obtained in nine patients with
      pilocytic astrocytomas (PA) and to discuss the original functional issues of this
      technique. METHOD: Nine patients with pathologically proven PA underwent
      conventional and perfusion MR imaging. Various areas of relative cerebral blood
      volume (rCBV) within the tumors were obtained. The maximum rCBV ratios were
      identified and considered as representative of the tumor. The results were
      compared with the pathological findings. RESULTS: In all patients, rCBV was <1.5
      (mean 1) and the signal intensity curve overshot the baseline. CONCLUSION: PA
      tend to have low rCBV values and a first-pass curve that crosses the baseline.
      These characteristics may be explained by the histological profile of the tumoral
      vascularity and are of relevance in the identification of these rare tumors.

PMID- 17530238
TI  - Effect of smooth muscle relaxant drugs on proximal human ureteric activity in
      vivo: a pilot study.
AB  - Drugs are increasingly being used to promote stone passage in renal colic.
      Diclofenac, nifedipine and tamsulosin cause ureteric smooth muscle relaxation in
      vitro; however, in clinical trials nifedipine and tamsulosin promote stone
      passage whereas diclofenac has no apparent benefit. We adapted a ureteric
      pressure transducer catheter in an attempt to compare the human ureteric response
      to these drugs in vivo. The catheter was inserted into the contralateral ureter
      following ureteroscopy for stone disease. Contraction frequency, pressure and
      velocity measurements were recorded at 24 h. Each patient was randomly allocated
      to receive oral diclofenac, nifedipine or tamsulosin. Measurements were taken
      following drug administration. Eighteen patients (mean age 50 years) were
      recruited. Two patients were excluded intraoperatively and three required early
      removal of the catheter. Prior to drug administration, the mean number of
      contractions recorded was 0-4.1/min and the peak contraction pressure ranged from
      11 to 35 mmHg. Conduction velocity ranged from 1.5 to 2.6 cm/s. Ureteric
      peristalsis persisted in all patients despite these drugs. Diclofenac and
      nifedipine produced inconsistent ureteric pressure responses but had little
      effect on contraction frequency. Tamsulosin significantly reduced ureteric
      pressure but had no effect on contraction frequency. There are many limitations
      associated with the use of ureteric catheters, however, they may provide some
      useful information when used to record the response to an intervention in the
      same patient. These preliminary results suggest a reduction in pressure
      generation may be the essential factor in the promotion of stone passage. More
      work is required but these drugs may work by preventing the increased,
      uncoordinated muscular activity seen in renal colic whilst maintaining
      peristalsis, thereby promoting stone passage.

PMID- 17530239
TI  - A role for US screening in juvenile idiopathic arthritis.

PMID- 17530240
TI  - Assessment of extrahepatic abdominal extension in primary malignant liver tumours
      of childhood.
AB  - Imaging is a crucial part of the evaluation of children with primary liver
      malignancies. In addition to staging the intrahepatic extent of the tumour, the
      2005 revision of the PRETEXT system specifies certain criteria for assessment of
      extrahepatic disease. This article reviews the imaging findings of two of these
      criteria: direct extrahepatic extension of the tumour (E1, E1a, E2, E2a) and
      tumour rupture at diagnosis (H1).

PMID- 17530241
TI  - Cavitating pulmonary tuberculosis in children: correlating radiology with
      pathogenesis.
AB  - BACKGROUND: Cavitating pulmonary tuberculosis (PTB) is generally known as a
      disease of adults, with children typically having features of primary PTB.
      OBJECTIVE: To group children with PTB and cavities according to possible
      pathogenesis by evaluating the clinical and radiological findings. MATERIALS AND
      METHODS: The clinical and radiological findings in ten randomly selected children
      with PTB and cavitations on chest radiographs were retrospectively reviewed and
      evaluated. RESULTS: Three groups emerged: group 1 (four children) had cavities,
      usually single and unilateral in the classic upper lobe distribution of
      postprimary PTB; group 2 (three children) developed progressive primary spread of
      disease with extensive and bilateral pulmonary cavities; and group 3 (three
      children) developed cavities secondary to airway obstruction by mediastinal lymph
      nodes with consequent distal collapse and consolidation. Children in group 1
      responded well to treatment and had unremarkable recoveries. Children in group 2
      were all below 2 years of age with complicated recoveries. Children in group 3
      had frequent complications resulting in one fatality. CONCLUSION: Cavities in PTB
      in children may arise by one of three possible mechanisms with a relatively equal
      incidence. A study is underway to determine the incidence of cavity formation
      associated with mediastinal lymphadenopathy and airway obstruction.

PMID- 17530242
TI  - Cloning, sequencing, and cell surface expression pattern of bovine immunoreceptor
      NKG2D and adaptor molecules DAP10 and DAP12.
AB  - NKG2D is an activating lectin-like receptor that initiates natural killer (NK)
      cell responses against transformed tumor cells expressing its ligands, i.e.,
      molecules related to major histocompatibility complex (MHC) class I molecules.
      NKG2D lacks signaling elements in its cytoplasmic domain and can deliver
      stimulatory signals only in association with transmembrane adaptor proteins DAP10
      or DAP12. The complementary DNAs (cDNAs) encoding the bovine homologues of NKG2D
      and the adaptor proteins DAP10 and DAP12 were cloned by reverse transcriptase
      polymerase chain reaction (RT-PCR) from resting bovine peripheral blood
      mononuclear cells (PBMC) and sequenced. Comparison with human, pig, and mouse
      sequences showed that bovine NKG2D is most similar to pig NKG2D and short mouse
      NKG2D (NKG2D-S). Similar to its human, mouse, and pig homologues, the cDNA for
      bovine DAP10 codes for a phosphatidyl-inositol-3 (PI-3) kinase-binding site
      (YxxM) in its cytoplasmic region. Finally, similar to its human, mouse, and pig
      homologues, the cDNA encoding bovine DAP12 demonstrates one tyrosine-based
      activated motif (ITAM) in its cytoplasmic domain. Bovine NKG2D cell surface
      expression was analyzed by flow cytometry on HEK 293 cells transiently
      transfected with cDNA expression vectors encoding COOH-terminal polyhistidine
      tagged NKG2D and NH(2)-terminal Flag-tagged DAP10 and DAP12. Confirming previous
      findings for short mouse NKG2D-S, bovine NKG2D immunoreceptor could associate
      with either DAP10 or DAP12 adaptor protein for its cell surface expression.

PMID- 17530243
TI  - Isolation and properties of a levo-lactonase from Fusarium proliferatum ECU2002:
      a robust biocatalyst for production of chiral lactones.
AB  - A fungus strain ECU2002, capable of enantioselectively hydrolyzing chiral
      lactones to optically pure hydroxy acids, was newly isolated from soil samples
      through two steps of screening and identified as Fusarium proliferatum
      (Matsushima) Nirenberg. From the crude extract of F. proliferatum ECU2002, a
      novel levo-lactonase was purified to homogeneity, with a purification factor of
      460-folds and an overall yield of 9.7%, by ultrafiltration, acetone
      precipitation, and chromatographic separation through DEAE-Toyopearl, Butyl
      Toyopearl, Hydroxyapatite, Toyoscreen-Super Q, and TSK-gel columns. The purified
      enzyme is a monomer; with a molecular mass of ca 68 kDa and a pI of 5.7 as
      determined by two-dimensional electrophoresis. The catalytic performance of the
      partially purified levo-lactonase was investigated, giving temperature and pH
      optima at 50 degrees C and 7.5, respectively, for gamma-butyrolactone hydrolysis.
      The substrate specificity of the partially purified lactonase was also examined
      using several useful lactones, among which alpha-hydroxy-gamma-butyrolactone was
      the best substrate, with 448-fold higher lactonase activity as compared to gamma
      butyrolactone. The F. proliferatum lactonase preferentially hydrolyzed the levo
      enantiomer of butyrolactones, including beta-butyrolactone, alpha-hydroxy-gamma
      butyrolactone, alpha-hydroxy-beta,beta-dimethyl-gamma-butyrolactone
      (pantolactone), and beta-hydroxy-gamma-butyrolactone, affording (+)-hydroxy acids
      in high (94.8 approximately 98.2%) enantiomeric excesses (ee) and good
      conversions (38.2 approximately 44.2%). A simple immobilization of the crude
      lactonase with glutaraldehyde cross-linking led to a stable and easy-to-handle
      biocatalyst for catalytic resolution of chiral lactones. The immobilized
      lactonase also performed quite well in repeated batch resolution of dl
      pantolactone at a concentration of 35% (w/v), retaining 67% of initial activity
      after ten cycles of reaction (corresponding to a half life of 20 cycles) and
      affording the product in 94 approximately 97% ee, which can be easily enhanced to
      >99% ee after the d-hydroxy acid was chemically converted into l-lactone and
      crystallized.

PMID- 17530244
TI  - Blue-white selection of regulatory genes that affect the expression of
      dehalogenase IVa of Burkholderia cepacia MBA4.
AB  - We have developed a method for rapid screening of genes that affected the
      expression of dehalogenase IVa of Burkholderia cepacia MBA4. The promoter region
      of the dehalogenase gene was used to drive the expression of a beta-galactosidase
      gene. A plasmid containing this reporter was first electroporated into MBA4, and
      a Tn5 containing suicidal plasmid was introduced subsequently. The use of
      electroporation was necessary because Escherichia coli mediated transconjugation
      was ineffective in plasmid-carrying MBA4. The number of integrants generated was
      directly proportional to the amount of plasmid DNA used. Integrants with an
      elevated beta-galactosidase activity were isolated. Mutants with a disruption in
      a putative iron-transporter gene and in a putative response regulator receiver
      gene were identified. The basal dehalogenase transcript levels of these mutants
      were higher than the wild type. These mutants also grow faster than the wild type
      in chloroacetate-containing medium. This methodology of isolating regulatory
      mutants is theoretically feasible and convenient for any kinds of bacteria.

PMID- 17530245
TI  - Microbial tannases: advances and perspectives.
AB  - In the last years, tannase has been the subject of a lot of studies due to its
      commercial importance and complexity as catalytic molecule. Tannases are capable
      of hydrolyzing complex tannins, which represent the main chemical group of
      natural anti-microbials occurring in the plants. The general outline of this work
      includes information of the substrates, the enzyme, and the applications. This
      review considers in its introduction the concepts and history of tannase and
      explores scientific and technological aspects. The "advances" trace the route
      from the general, molecular, catalytic, and functional information obtained under
      close to optimal conditions for microbial production through purification,
      description of the enzyme properties, and the commercial applications to the
      "perspectives" including expression studies, regulation, and potential uses;
      aspects related to the progress in our understanding of tannin biodegradation are
      also included.

PMID- 17530246
TI  - Technical errors in MR arthrography.
AB  - This article discusses potential technical problems of MR arthrography. It starts
      with contraindications, followed by problems relating to injection technique,
      contrast material and MR imaging technique. For some of the aspects discussed,
      there is only little published evidence. Therefore, the article is based on the
      personal experience of the author and on local standards of procedures. Such
      standards, as well as medico-legal considerations, may vary from country to
      country. Contraindications for MR arthrography include pre-existing infection,
      reflex sympathetic dystrophy and possibly bleeding disorders, avascular necrosis
      and known allergy to contrast media. Errors in injection technique may lead to
      extra-articular collection of contrast agent or to contrast agent leaking from
      the joint space, which may cause diagnostic difficulties. Incorrect
      concentrations of contrast material influence image quality and may also lead to
      non-diagnostic examinations. Errors relating to MR imaging include delays between
      injection and imaging and inadequate choice of sequences. Potential solutions to
      the various possible errors are presented.

PMID- 17530247
TI  - Somatostatin receptor scintigraphy using 99mTc-EDDA/HYNIC-TOC in patients with
      medullary thyroid carcinoma.
AB  - PURPOSE: Several new somatostatin analogues have been developed for the diagnosis
      and therapy of different tumours. Since somatostatin receptors are often over
      expressed in medullary thyroid carcinoma (MTC), the aim of our study was to
      evaluate the utility of scintigraphy with the somatostatin analogue (99m)Tc
      EDDA/HYNIC-TOC in MTC in comparison with other diagnostic techniques. METHODS:
      Forty-five patients with MTC, aged 14-83 years, were investigated. Scintigraphy
      using (99m)Tc-EDDA/HYNIC-TOC (Tektrotyd) was performed 2 and 4 h post injection
      of 740 MBq (20 mCi) of the tracer. Other imaging techniques were also applied and
      analysed in individual cases (ultrasonography, computed tomography, (99m)Tc(V)
      DMSA, (131)I-MIBG, (99m)Tc-MDP, (111)In-DTPA-octreotide and (18)F-FDG-PET) and
      compared with (99m)Tc-EDDA/HYNIC-TOC. RESULTS: In group 1 (eight patients before
      thyroidectomy), uptake of the tracer was found in the primary tumours. In group 2
      (six patients with remission), a false positive result was found in one patient;
      in the remaining five patients, no pathological foci were visualised. In group 3
      (31 patients with post-surgical hypercalcitoninaemia), scintigraphy was true
      positive in 23 patients (74.2%): uptake in the thyroid bed was found in five
      patients, in the lymph nodes in 18 and in bone metastases in four. Using (99m)Tc
      EDDA/HYNIC-TOC scintigraphy, the overall sensitivity was 79.5%, specificity
      83.3%, accuracy 80.0%, positive predictive value 96.9% and negative predictive
      value 38.5%. CONCLUSION: (99m)Tc-EDDA/HYNIC-TOC is clinically useful for
      scintigraphy in the follow-up of patients with MTC. It can be used in clinical
      practice for preoperative evaluation, for localisation of local recurrence or
      distant metastases and particularly for therapy decision making.

PMID- 17530248
TI  - Non-enhanced CT versus contrast-enhanced CT in integrated PET/CT studies for
      nodal staging of rectal cancer.
AB  - PURPOSE: The purpose of the present study was to determine the diagnostic
      accuracy of non-enhanced CT and contrast-enhanced CT in integrated PET/CT studies
      for preoperative nodal staging of rectal cancer. METHODS: Retrospective analysis
      was performed in 53 patients with pathologically proven rectal cancer who had
      been referred for preoperative staging. All patients underwent integrated PET/CT
      consisting of non-enhanced and contrast-enhanced CT followed by whole-body
      fluorine-18-fluorodeoxyglucose ([(18)F]FDG) PET. Both non-enhanced and contrast
      enhanced PET/CT images were evaluated separately by two observers in consensus.
      The reference standard was histopathologic results. For nodal staging of rectal
      cancer, we compared diagnostic accuracy on a per-patient basis between the two
      modalities. RESULTS: Nodal staging was correctly determined with non-enhanced
      studies in 37 patients (70%) and with contrast-enhanced studies in 42 patients
      (79%). On a per-patient basis, sensitivity, specificity, positive predictive
      value, negative predictive value, and accuracy of regional lymph node staging
      were 85%, 68%, 83%, 72%, and 79%, respectively, with contrast-enhanced studies,
      and 85%, 42%, 73%, 62%, and 70%, respectively, with non-enhanced studies. The
      difference in the accuracy of nodal staging between the two modalities was not
      significant (p = 0.063). Compared with non-enhanced studies, contrast-enhanced
      studies determined more correctly the status of pararectal lymph nodes (p =
      0.002), internal iliac lymph nodes (p = 0.004), and obturator lymph nodes (p <
      0.0001). CONCLUSION: Contrast-enhanced PET/CT is superior to non-enhanced PET/CT
      for precise definition of regional nodal status in rectal cancer.

PMID- 17530249
TI  - In vivo assessment of cardiac insulin resistance by nuclear probes using an
      iodinated tracer of glucose transport.
AB  - PURPOSE: Insulin resistance, implying depressed cellular sensitivity to insulin,
      is a risk factor for type 2 diabetes and cardiovascular disease. This study is
      the first step towards the development of a technique of insulin resistance
      measurement in humans with a new tracer of glucose transport, [(123)I]6-deoxy-6
      iodo-D-glucose (6DIG). METHODS: We investigated 6DIG kinetics in anaesthetised
      control rats and in three models of insulin-resistant rats: fructose fed, Zucker
      and ZDF. The study of myocardial 6DIG activity was performed under two
      conditions: first, 6DIG was injected under the baseline condition and then it was
      injected after a bolus injection of insulin. After each injection, radioactivity
      was measured over 45 min by external detection via NaI probes, in the heart and
      blood. A tri-compartment model was developed to obtain fractional transfer
      coefficients of 6DIG from the blood to the heart. RESULTS: These coefficients
      were significantly increased with insulin in control rats and did not change
      significantly in insulin-resistant rats. The ratio of the coefficient obtained
      under insulin to that obtained under basal conditions gave an index of cardiac
      insulin resistance for each animal. The mean values of these ratios were
      significantly lower in insulin-resistant than in control rats: 1.16 +/- 0.06 vs
      2.28 +/- 0.18 (p < 0.001) for the fructose-fed group, 0.92 +/- 0.05 vs 1.62 +/-
      0.25 (p < 0.01) for the Zucker group and 1.34 +/- 0.06 vs 2.01 +/- 0.26 (p <
      0.05) for the ZDF group. CONCLUSION: These results show that 6DIG could be a
      useful tracer to image cardiac insulin resistance.

PMID- 17530252
TI  - Erroneously elevated immature reticulocyte counts in leukemic patients determined
      using a Sysmex XE-2100 hematology analyzer.
AB  - The immature reticulocyte fraction (IRF) in peripheral blood, as determined by
      automated reticulocyte analysis, is calculated using the sum of medium and highly
      fluorescent reticulocyte numbers and provides information about erythropoietic
      activity in bone marrow. The purpose of this study was to investigate erroneously
      elevated IRF in leukemic patients, as determined using a Sysmex XE-2100
      hematology analyzer (Sysmex, Kobe, Japan). Normal reticulocyte scattergram
      patterns show regions corresponding to reticulocytes located between matured RBCs
      and an upper particle (UPP) region, which show a continuum of non-separated
      fraction. The UPP represents erythroblasts and some immature reticulocytes. As a
      control group, peripheral blood was taken from patients with benign hematologic
      diseases, and their reticulocyte scattergrams all showed a normal pattern; UPP
      values were all less than 100. However, the reticulocyte scattergrams of 5 of 11
      leukemia patients showed abnormal patterns and displayed a gap between RBC and
      reticulocyte regions. Three patients showed a flag with a message such as "RET
      Abn Scattergram". IRF results were elevated in these five patients, and their UPP
      values were above 100. For the remaining six leukemia patients with a normal
      reticulocyte scattergram pattern, immature reticulocytes were not markedly
      increased, and UPP values were less than 100. The findings of the present study
      demonstrate that IRF results may be erroneously elevated in leukemia patients and
      indicate that hematologists should examine reticulocyte scattergrams and UPP
      values carefully.

PMID- 17530250
TI  - Correlation of 18F-FLT and 18F-FDG uptake on PET with Ki-67 immunohistochemistry
      in non-small cell lung cancer.
AB  - PURPOSE: The nucleoside analogue 3'-deoxy-3'-(18)F-fluorothymidine (FLT) has
      recently been introduced for imaging cell proliferation with positron emission
      tomography (PET). We prospectively evaluated whether FLT uptake reflects
      proliferative activity as indicated by the Ki-67 index in non-small cell lung
      cancer (NSCLC), in comparison with 2-deoxy-2-(18)F-fluoro-D-glucose (FDG).
      METHODS: A total of 18 patients with newly diagnosed NSCLC were examined with
      both FLT PET and FDG PET. PET imaging was performed at 60 min after each
      radiotracer injection. Tumour lesions were identified as areas of focally
      increased uptake, exceeding background uptake in the lungs. For semi-quantitative
      analysis, the maximum standardised uptake value (SUV) was calculated.
      Proliferative activity as indicated by the Ki-67 index was estimated in tissue
      specimens. Immunohistochemical findings were correlated with SUVs. RESULTS: The
      sensitivity of FLT and FDG PET for the detection of lung cancer was 72% and 89%,
      respectively. Four of the five false-negative FLT PET findings occurred in
      bronchiolo-alveolar carcinoma. The mean FLT SUV was significantly lower than the
      mean FDG SUV. A significant correlation was observed between FLT SUV and Ki-67
      index (r = 0.77; p < 0.0002) and for FDG SUV (r = 0.81; p < 0.0001). CONCLUSION:
      The results of this preliminary study suggest that, compared with FDG, FLT may be
      less sensitive for primary staging in patients with NSCLC. Although FLT uptake
      correlated significantly with proliferative activity in NSCLC, the correlation
      was not better than that for FDG uptake.

PMID- 17530253
TI  - Traveling waves in the discrete fast buffered bistable system.
AB  - We study the existence and uniqueness of traveling wave solutions of the discrete
      buffered bistable equation. Buffered excitable systems are used to model, among
      other things, the propagation of waves of increased calcium concentration, and
      discrete models are often used to describe the propagation of such waves across
      multiple cells. We derive necessary conditions for the existence of waves, and,
      under some restrictive technical assumptions, we derive sufficient conditions.
      When the wave exists it is unique and stable.

PMID- 17530254
TI  - Steric hindrance effects on surface reactions: applications to BIAcore.
AB  - Because surface-volume reactions occur in many biological and industrial
      processes, understanding the rate of such reactions is important. The BIAcore
      surface plasmon resonance (SPR) biosensor for measuring rate constants has such a
      geometry. Though several models of the BIAcore have been presented, few take into
      account that large ligand molecules can block multiple receptor sites, thus
      skewing the sensogram data. In this paper some general mathematical principles
      are stated for handling this phenomenon, and a surface-reaction model is
      presented explicitly. An integro-partial differential equation results, which can
      be simplified greatly using perturbation techniques, yielding linear and
      nonlinear integrodifferential equations. Explicit and asymptotic solutions are
      constructed for cases motivated by experimental design. The general analysis can
      provide insight into surface-volume reactions occurring in various contexts. In
      particular, the steric hindrance effect can be quantified with a single
      dimensionless parameter.

PMID- 17530255
TI  - Soliton behaviour in a bistable reaction diffusion model.
AB  - We analyze a generic reaction-diffusion model that contains the important
      features of Turing systems and that has been extensively used in the past to
      model biological interesting patterns. This model presents various fixed points.
      Analysis of this model has been made in the past only in the case when there is
      only a single fixed point, and a phase diagram of all the possible instabilities
      shows that there is a place where a Turing-Hopf bifurcation occurs producing
      oscillating Turing patterns. In here we focus on the interesting situation of
      having several fixed points, particularly when one unstable point is in between
      two equally stable points. We show that the solutions of this bistable system are
      traveling front waves, or solitons. The predictions and results are tested by
      performing extensive numerical calculations in one and two dimensions. The
      dynamics of these solitons is governed by a well defined spatial scale, and
      collisions and interactions between solitons depend on this scale. In certain
      regions of parameter space the wave fronts can be stationary, forming a pattern
      resembling spatial chaos. The patterns in two dimensions are particularly
      interesting because they can present a coherent dynamics with pseudo spiral
      rotations that simulate the myocardial beat quite closely. We show that our
      simple model can produce complicated spatial patterns with many different
      properties, and could be used in applications in many different fields.

PMID- 17530256
TI  - [Ovarian tumors. New techniques for prognostic evaluation].

PMID- 17530257
TI  - Perinuclear and nuclear envelope localizations of Arabidopsis Ran proteins.
AB  - Using phragmoplastin-interacting protein 1 (PhrIP1) as bait, we isolated an
      Arabidopsis cDNA encoding Ran2, a small Ras-like GTP-binding protein. The
      interaction between PhrIP1 and Ran2 was confirmed by an in vitro protein-protein
      interaction assay with purified Ran2 and PhrIP1. The plant Ran2 shares high
      sequence homology, 78 and 86% at the amino acid level, with human Ran/TC4 and C.
      elegans Ran, respectively. Our results obtained from enzyme assays and Western
      blot analysis show that Ran2 has intrinsic GTPase activity and is present in the
      soluble fraction of Arabidopsis seedling extract. Fluorescent microscopy using
      anti-Ran2 antibody revealed that the Ran protein is localized in the perinuclear
      region with the highest concentration at the nuclear envelope. In contrast to its
      animal counterparts that are present in the nucleoplasm, the Ran protein is
      absent inside the nucleus. These results suggest that plant Ran proteins may be
      involved in mediation of nucleocytoplasmic transport and assembly of the nuclear
      envelope after karyokinesis in plant cells.

PMID- 17530258
TI  - RevoLix vaporesection of the prostate: initial results of 54 patients with a 1
      year follow-up.
AB  - Multiple laser systems for the treatment of benign prostatic hyperplasia (BPH)
      have been introduced. Current laser systems have limitations due to their laser
      physics. The RevoLix laser combines the advantages of the Holmium:YAG laser with
      the comfort of a continuous wave (cw) laser beam. This study reports the
      preliminary results of vaporesection (simultaneous vaporization and resection) of
      the prostate, using the 2 microm cw laser. A total of 54 consecutive patients
      were treated with the 70 W RevoLix laser for BPH. The mean age was 61 years. Mean
      prostate volume was 30.3 cc. A 550 microm RigiFib bare-ended fiber was used in
      combination with a 26 French laser resectoscope. Measured outcomes were resection
      time, decrease in hemoglobin and transfusion rate. Furthermore, the catheter
      time, improvement in the urinary flow rate (Q(max)), post-voiding residual urine
      (PVR), International Prostate Symptom Score (IPSS) and Quality of Life Index
      (QoL) were recorded. Average resection time was 52 min. After crossing the
      learning curve, a tissue ablation of 1.5 g/min was possible. Transfusions were
      not necessary in any patient. Catheter time was 1.7 days. Q(max) significantly
      improved from 4.2 to 20.1 ml on average. PVR decreased from 86 to 12 ml. IPSS and
      QoL-Score improved from 19.8 to 6.9 and 4 to 1, respectively. No patient required
      re-hospitalization. These preliminary results indicate that RevoLix vaporesection
      of the prostate is safe and efficient. One-year follow-up data showed a
      significant improvement in voiding symptoms and patients' quality of life. A
      longer follow-up is needed to prove the durability of these promising results.

PMID- 17530259
TI  - Laser treatment of benign prostatic hyperplasia.
AB  - To evaluate the role of lasers that allow acute removal of obstructing tissue in
      the surgical treatment of benign prostatic hyperplasia (BPH). A MEDLINE search
      over the last 6 years focused on randomized trials, large case series and review
      articles. A total of more than 4,000 patients were analyzed with respect to the
      morbidity and outcome, and the advantages and disadvantages of the various
      lasers. Laser treatment of BPH has evolved from coagulation to enucleation. Blood
      loss is significantly reduced as compared to transurethral resection and open
      prostatectomy. Ablative/vaporizing techniques have recently become popular again
      with the marketing of new high-powered 80 W potassium-titanyl-phosphate (KTP) and
      100 W holmium lasers. Vaporization immediately removes obstructing tissue, but
      tissue specimen cannot be obtained. KTP short-term results are promising, but
      long-term results and randomized trials are lacking. Postoperative volume
      reduction is less than with holmium laser enucleation of the prostate (HoLEP),
      and the KTP laser can be used for BPH treatment only. HoLEP allows whole lobes of
      the prostate to be removed. Prostates of all sizes can be operated on. It is at
      least as safe and effective as TURP and open prostatectomy, with significantly
      lower morbidity, as shown by several well-designed randomized clinical trials. It
      provides specimen for histological evaluation. In addition, the holmium laser can
      be used for the endourological treatment of stones, strictures and tumors. HoLEP
      appears to be a size-independent new "gold standard" in the surgical treatment of
      BPH.

PMID- 17530261
TI  - [Differential diagnosis and treatment options for conjunctival tumors].
AB  - The diagnostic classification of most conjunctival tumors is based on case
      history, inspection, and examination with the slit lamp microscope. Further
      imaging procedures are rarely indicated when malignant processes are not
      circumscribed. Clinical classification then also includes palpation and
      echographic examination of regional lymph nodes. Pigmented and nonpigmented
      melanocytic nevi are the most frequent conjunctival tumors. An important
      practical biomicroscopic cardinal symptom of the most frequent nevi is the
      presence of epithelial pseudocysts. Essential in practice is the
      histopathological confirmation of the clinical diagnosis, e.g., distinguishing
      between nonpigmented melanomas and sebaceous gland carcinomas with a pagetoid
      growth pattern or squamous cell carcinomas. Depending on the course and findings,
      the following therapeutic measures can be indicated: cryotherapy, chemotherapy,
      radiotherapy, modified enucleation, orbital exenteration, or a combination of
      different methods.

PMID- 17530260
TI  - Epidemiology of urinary bladder cancer: from tumor development to patient's
      death.
AB  - Urinary bladder cancer (UBC) ranks ninth in worldwide cancer incidence. It is
      more frequent in men than in women. We review the main established/proposed
      factors, both environmental and genetic, associated with bladder cancer etiology
      and prognosis. Data were extracted from previous reviews and original articles
      identified from PubMed searches, reference lists, and book chapters dealing with
      the reviewed topics. Evaluation and consensus of both the contribution of each
      factor in bladder cancer burden and the appropriateness of the available
      evidences was done during an ad hoc meeting held during the 18th Congress of the
      European Society for Urological Research. Cigarette smoking and specific
      occupational exposures are the main known causes of UBC. Phenacetin,
      chlornaphazine and cyclophosphamide also increase the risk of bladder cancer.
      Chronic infection by Schistosoma haematobium is a cause of squamous cell
      carcinoma of the bladder. NAT2 slow acetylator and GSTM1 null genotypes are
      associated with an increased risk of this cancer. Vegetables and fresh fruits
      protect against this tumor. Regarding prognosis, there is little knowledge on the
      predictive role of environmental exposures and genetic polymorphisms on tumor
      recurrence and progression and patient's death. Although active tobacco smoking
      is the most commonly studied factor, no definitive conclusion can be drawn from
      the literature. More research is needed regarding the effect of complex
      etiological factors in bladder carcinogenesis. Subgroup analysis according to
      stage, grade, and molecular features may help in identifying specific etiological
      and prognostic factors involved in different bladder cancer progression pathways.

PMID- 17530262
TI  - [Ocular toxoplasmosis].
AB  - Toxoplasmosis is a parasitic zoonosis which occurs worldwide and is an important
      cause of blindness. The infection is naturally acquired by the ingestion of
      oocysts excreted by infected cats or by ingestion of tissue cysts in undercooked
      or raw meat. Primary infection during pregnancy may result in a congenital
      infection. Toxoplasmic retinochoroiditis is the most common cause of posterior
      uveitis in immunocompetent patients. Depending on the patient's age, ocular
      symptoms vary presenting with reduced visual acuity, strabismus, and nystagmus in
      young children - in adults decreased vision and floaters are most frequently
      reported. Active toxoplasmic retinochoroiditis typically presents as grey-white
      retinal necrosis with choroiditis, vasculitis and vitritis. However, atypical
      presentations including neuroretinitis, papillitis, Fuchs-like anterior uveitis,
      scleritis and acute retinal necrosis have been described. The diagnosis is based
      on clinical findings and can be supported by the detection of antibodies and
      Toxoplasma gondii DNA. Toxoplasmosis therapy includes antimicrobial drugs and
      corticosteroids. There are several regimens with different drug combinations
      including, among others, pyrimethamine, sulfadiazine, clindamycin, and
      trimethoprim-sulfamethoxazol. The prognosis for ocular toxoplasmosis is favorable
      in immunocompetent individuals, as long as the central macula is not directly
      involved. The present article reviews the epidemiology, pathogenesis, clinical
      presentation and management of toxoplasmic retinochoroiditis.

PMID- 17530263
TI  - Methodological quality of randomised controlled trials comparing short-term
      results of laparoscopic and conventional colorectal resection.
AB  - BACKGROUND: Randomised, controlled trials (RCT) and systematic reviews of RCT
      with meta-analysis are considered to be of highest methodological quality and
      therefore are given the highest level of evidence (Ia/b). Although, "low-quality"
      RCT may be downgraded to level of evidence IIb, the methodological quality of
      each individual RCT is not respected in detail in this classification of the
      level of evidence. MATERIALS AND METHODS: Within a systematic Cochrane Review of
      RCT on short-term benefits of laparoscopic or conventional colorectal resections,
      the methodological quality of all included RCT was evaluated. All RCT were
      assessed by the Evans and Pollock questionnaire (E and P increasing quality from
      0-100) and the Jadad score (increasing quality from 0-5). RESULTS: Publications
      from 28 RCT printed from 1996 to 2005 were included in the analysis.
      Methodological quality of RCT was only moderate [E & P 55 (32-84); Jadad 2 (1
      5)]. There was a significant correlation between the E & P and the Jadad score (r
      = 0.788; p < 0.001). Methodological quality of RCT slightly increased with
      increasing number of patients included (r = 0.494; p = 0.009) and year of
      publication (r = 0.427; p = 0.03). Meta-analysis of all RCT yielded clinically
      relevant differences for overall and local morbidity when compared to meta
      analysis of "high-quality" (E & P > 70) RCT only. CONCLUSION: The methodological
      quality of reports of RCT comparing laparoscopic and open colorectal resection
      varies considerably. In a systematic review, methodological quality of RCT should
      be assessed because meta-analysis of "high-quality" RCT may yield different
      results than meta-analysis of all RCT.

PMID- 17530264
TI  - Surgical intervention in children with Crohn's disease.
AB  - INTRODUCTION: Crohn's disease (CD) causes chronic inflammation of the
      gastrointestinal tract leading to extensive medical treatments and surgery with
      two thirds of patients having surgery over their lifetime. In this study, we
      reviewed the pediatric population at the British Columbia Children's Hospital
      diagnosed with CD and examined their demographics and treatments, in particular
      assessing those who ultimately underwent surgery. MATERIALS AND METHODS: Two
      hundred and eighty children (median age 11.9 years [CI 11.5-12.28]) diagnosed
      with CD from January 1994 to December 2003 were included. Demographic data were
      documented including age, ethnicity, duration of symptoms before diagnosis,
      treatment to date and surgical parameters. Comparison was made between operative
      and non-operative patients including involvement of disease, medical treatment,
      complications and recurrence of disease leading to repeat operations. RESULTS:
      Fifty-five (19.6%) children had surgical procedures. There was a significant
      increase in surgery in those patients who had not received immunomodulator
      therapy before surgery (odds ratio 1.95 [CI 1.02-3.73]). We also observed that
      those CD patients with extensive small intestinal involvement had lower
      likelihood of having surgery (odds ratio 0.386 [CI 0.145-1.033]). No significant
      difference was found between the two groups with regard to age of diagnosis (p =
      0.41), duration of symptoms (p = 0.22), gender (p = 0.50) or ethnicity (p =
      0.451). CONCLUSION: There was an increased incidence of surgery in those patients
      who were not treated with immunomodulator therapy. In addition, children with
      extensive as opposed to isolated small intestinal disease were less likely to
      have surgery in childhood.

PMID- 17530265
TI  - [Growth factors].
AB  - Growth factors such as PDGF, VEGF and TGF-beta play a pivotal role in the
      regulation and differentiation of different cell types in the connective tissue,
      for example fibroblasts and endothelial cells, and in the immune system.
      Pathophysiologically, these growth factors are thought to play a central role in
      tumorigenesis, and the use of their inhibitors has led to substantial
      improvements in tumor therapy. Recent findings also support an important role for
      growth factors in inflammatory rheumatoid diseases. New developments in the
      understanding and potential role of these factors in the pathophysiology of
      rheumatic diseases will be discussed.

PMID- 17530266
TI  - Changes in distribution pattern of CD8 lymphocytes in the scalp in alopecia
      areata during treatment with diphencyprone.
AB  - For many years, the role of T lymphocytes was hypothesized as being a major
      factor responsible for hair loss in alopecia areata (a.a.). While numerous
      lymphocytic populations were found around hair bulbs, changes in their
      distribution patterns in the skin during the course and recovery of the disease
      remain unknown. In the present study, distribution of CD8 lymphocytes in biopsies
      obtained from a.a. patients was measured before and during treatment using
      diphencyprone (DCP). Results show about a 600% increase in the number of CD8
      lymphocytes under the epithelium and about a 250% increase around hair bulbs and
      other epidermal appendages during the study. These results were more significant
      in a group, which had good clinical response to the treatment. No change in the
      quantity of CD8 lymphocytes was observed around the blood vessels. Since CD8
      lymphocytes are considered to be directly involved in the hair destruction
      process in a.a., their increased number around hair bulbs followed by hair
      regrowth may suggest that during DCP treatment they regain normal reactivity to
      hair antigens.

PMID- 17530267
TI  - Detection of Mycobacterium leprae DNA in skin lesions of leprosy patients by PCR
      may be affected by amplicon size.
AB  - Despite the high sensitivity and specificity of PCR for infectious disease
      diagnostics, it has presented low sensitivity for Mycobacterium leprae DNA
      detection in the tuberculoid pole (TT and BT) of leprosy. In order to demonstrate
      the effect of amplicon size on the efficacy of PCR detection of M. leprae DNA in
      skin lesions of leprosy patients, two pairs of primers targeting the M. leprae
      genomic DNA, RLEP3 (X17153), were used to amplify fragments of 372 and 130-bp
      until their PCR end-points were reached after 40 reaction cycles. Skin biopsies
      of leprosy lesions in 110 non-treated patients were used for bacilloscopy index
      (BI) analysis and PCR tests. The 130-bp fragment was detected in 73.6% of samples
      (81/110), and classified as TT (40%), BT (55.5%), and 100% of BB, BL and LL. The
      372-bp fragment was detected in 52.7% and classified as TT (13.3%), BT (33.3%),
      BB (64.7%), BL (83.3%), and LL (95.2%). The BI of biopsies was positive in 39.1%
      of samples, classified as TT (0%), BT (2.2%), BB (64.7%), BL (91.6%), and LL
      (95.2%). The shorter amplicon (130-bp) has improved diagnosis by 20.9 and 34.5%
      in relation to the 372-bp fragment and the BI, respectively, and has shown a
      superior sensitivity (73.6%), specificity (100%) and accuracy (86.2%). The 130-bp
      amplicon could not detect % of positive BI of biopsies in BT cases. Therefore,
      for confirmatory diagnosis, we propose the use of PCR detection of the 130-bp
      genomic target, especially when the tuberculoid pole forms are considered, which
      has reached 51.6% of positivity in this group.

PMID- 17530269
TI  - Effects of an external nasal dilator strip (ENDS) compared to xylometazolin nasal
      spray.
AB  - Nasal blockage is a common complaint in Family Practice. Decongestive nosedrops
      are frequently employed therapeutic measures. Due to a considerable risk of abuse
      and side effects, alternatives are wanted. The purpose of this study was to
      elucidate to what extent ENDS might represent an alternative to decongestive nose
      sprays (DNS). The effects of DNS (xylometazolin) and ENDS (BreatheRight) on
      subjective and objective nasal blockage were compared in 89 patients. Main
      outcome measures were recordings of nasal symptom scores on visual analogue
      scales (VAS), minimal cross-sectional areas (MCA) and nasal cavity volumes (NCV)
      as measured by acoustic rhinometry (AR), and peak nasal inspiratory flow (PNIF).
      ENDS significantly increased the MCA and the NCV in the anterior 0.0-3.0 cm of
      the nose compared to DNS, but had no effect on MCA from 3.0 to 5.4 cm behind the
      nostrils. In contrast to DNS, ENDS had no effect on the posterior NCV. ENDS and
      DNS gave comparable increase in nasal inspiratory flow as measured by PNIF, and
      in the subject's own experience of nasal obstruction. ENDS may represent an
      alternative to DNS as a measure against nasal blockage.

PMID- 17530268
TI  - DNA content, Cyclooxygenase-2 expression and loss of E-cadherin expression do not
      predict risk of malignant transformation in oral lichen planus.
AB  - Oral lichen planus (OLP) may be associated with a small risk of malignant
      transformation of the oral mucosa. Using cases which had transformed, and those
      which had not, this study aimed to evaluate the potential of DNA content,
      expression of Cyclooxygenase-2 (Cox-2) and of epithelial (E)-cadherin as risk
      markers in lesions of OLP. We investigated 78 archival biopsies from; (1) 26 OLP
      patients with at least two biopsies, of whom seven presented OLP with epithelial
      dysplasia, followed by oral squamous cell carcinoma (OSCC) in five of them, (2)
      19 OLP patients with one biopsy taken. Image cytometry for measurement of DNA
      content and immunohistochemistry for visualisation of Cox-2 and E-cadherin
      expression were performed. All OLP biopsies investigated were classified as
      diploid, one OLP with epithelial dysplasia was tetraploid and all OSCC were
      diploid. Cox-2 was detected in the epithelium of all OLP specimens investigated,
      as well as in epithelial dysplasias and OSCC. Focal loss of E-cadherin expression
      was observed in basal keratinocytes in 88% of the OLP specimens investigated, in
      all epithelial dysplasias and OSCC. In conclusion, neither aneuploidy, Cox-2
      expression, nor loss of E-cadherin expression, were significant reliable markers
      to select OLP lesions at risk for development of OSCC in the present patient
      material.

PMID- 17530270
TI  - Does epinephrine infiltration in septoplasty make any difference? A double blind
      randomised controlled trial.
AB  - Infiltration of lignocaine with epinephrine is used with cocaine in septoplasty,
      in attempt to improve haemostasis and thereby improve the surgical field. This
      practice is widespread despite the lack of evidence to support its efficacy in
      the literature. Thirty patients undergoing septoplasty were randomised into two
      groups -- one in whom infiltration was performed with lignocaine (2%) with
      adrenaline (1:80,000) and a control group who received lignocaine (2%). Both
      groups of patients received intranasal application of cocaine paste prior to
      surgery. The surgeon and anaesthetist were blinded to the contents of the
      infiltration. The operative field was rated by the surgeon, and the blood loss
      calculated. No significant difference was demonstrated in blood loss or surgical
      field between the groups. However there was significant rise in systolic blood
      pressure in patients who received epinephrine. The use of epinephrine with
      cocaine paste does not improve haemostasis or surgical field. As the use of
      epinephrine is associated with cardiac arrhythmias, the authors suggest that
      combined use of cocaine paste and epinephrine infiltration should be avoided in
      septal surgery.

PMID- 17530271
TI  - Static magnetic field effect on the arterial baroreflex-mediated control of
      microcirculation: implications for cardiovascular effects due to environmental
      magnetic fields.
AB  - Increasing evidence suggests that time-varying and static magnetic fields in the
      environment might affect the cardiovascular system. To explore the underlying
      physiology, the effect of static magnetic fields (SMFs) on the carotid baroreflex
      control of microcirculation was studied. Twenty-four hemodynamic monitorings were
      performed in rabbits sedated by pentobarbital infusion (5 mg/kg/h) during
      experiments that lasted 120 min. Mean femoral artery blood pressure, heart rate,
      and ear lobe skin microcirculatory blood flow, measured by microphotoelectric
      plethysmogram (MPPG), were simultaneously recorded before and after a 40 min
      exposure of the sinocarotid baroreceptors to Nd(2)-Fe(14)-B alloy magnets (n =
      14) or sham magnets (n = 10, control series). The local SMF field was 350 mT, at
      the baroreceptors' site. Arterial baroreflex sensitivity (BRS) was estimated from
      heart rate/blood pressure response to intravenous bolus injections of
      nitroprusside and phenylephrine. A significant positive correlation was found
      between the SMF-induced increase in BRS (DeltaBRS = BRS(afterSMF) -
      BRS(priorSMF)) and the increment in microvascular blood flow (DeltaMPPG =
      MPPG(afterSMF) - MPPG(priorSMF)) (r = 0.66, p < 0.009). The SMF probably
      modulated the arterial baroreflex-mediated microcirculatory control. This could
      represent one possible mechanism how environmental magnetic fields act on the
      cardiovascular system, and a method how to complexly adjust macro- and
      microcirculation with potential clinical implementation.

PMID- 17530272
TI  - Chromatin breakdown by deoxyribonuclease1 promotes acetaminophen-induced liver
      necrosis: an ultrastructural and histochemical study on male CD-1 mice.
AB  - We analyzed in male wild-type (WT) and Dnase1 knockout (KO) CD-1 mice after
      acetaminophen (APAP)-intoxication the hepatolobular distribution of APAP-adducts
      in relation to DNA-damage by terminal deoxyribonucleotidyl-transferase dUTP nick
      end-labeling (TUNEL), the ultrastructural alterations of hepatocellular
      morphology and the intracellular localization of Dnase1. Treatment of WT-mice
      with 600 mg/kg APAP led to extensive pericentral necrosis. Electron microscopy
      (EM) demonstrated vesiculation of the rough endoplasmatic reticulum and swelling
      of mitochondria. Pericentral WT-hepatocyte nuclei exhibited pyknosis,
      karyorrhexis and karyolysis. In contrast, livers from treated KO-mice exhibited
      almost normal light microscopical structure and EM revealed only mild signs of
      hepatocellular damage. In WT-mice several layers of pericentral hepatocytes
      displayed APAP-adduct formation and subsequent DNA-damage, whereas in KO-animals
      only few cells were affected. Serum aminotransferases rose similarly in both
      mouse strains up to 12 h, thereafter increased only in WT-mice. Immunogold-EM
      revealed the translocation of Dnase1 from the rER into the nuclei of treated WT
      mice. In KO-mice, APAP-adduct formation was retarded and less extensive
      suggesting that detoxification of APAP must have been more effective in KO-mice
      possibly due to the lack of energy depletion otherwise caused by Dnase1-induced
      DNA-damage in WT-mice.

PMID- 17530274
TI  - Influence of muscle architecture on the torque and power-velocity characteristics
      of young and elderly men.
AB  - This study investigated the contribution of muscle architecture to the
      differences in the torque-velocity and power-velocity relationships between older
      (OM n = 9, aged 69-82 years) and younger men (YM n = 15, aged 19-35 years).
      Plantarflexors' (PF) maximal isometric and concentric torques were recorded at
      0.87, 1.75, 2.62, 3.49 and 4.36 rad s(-1). Physiological cross-sectional area
      (PCSA) was calculated as the ratio of muscle volume (determined by magnetic
      resonance imaging) to muscle fascicle length (Lf, measured by ultrasonography).
      GM PCSA and Lf of the OM were, respectively, 14.3% (P < 0.05) and 19.3% (P <
      0.05) smaller than of the YM. In the OM, GM maximum isometric torque and maximum
      contraction velocity (Vmax), estimated from Hill's equation were, respectively,
      48.5 and 38.2% lower (P < 0.001) than in the YM. At all contraction velocities,
      the OM produced less torque than the YM (46.3% of YM at 0.87 rad s(-1) to 14.7%
      at 4.36 rad s(-1), P < 0.001). Peak power (PP) of the OM was 80% lower than that
      of the YM and normalisation of PP to muscle volume only reduced this difference
      by 10%. Normalisation of torque to PCSA reduced, but did not eliminate,
      differences in torque between YM and OM (9.6%) and differences in torque/PCSA
      increased with contraction velocity (P < 0.05). After normalisation of velocity
      to Lf, the difference in Vmax between the OM and the YM was reduced to 15.9%.
      Thus, although muscle architecture contributes significantly to the differences
      in the torque- and power-velocity properties of OM and YM, other contractile
      factors, intrinsic to the muscle, seem to play a role. It is noteworthy that the
      deficit in PP between OM and YM is far greater than that of muscle torque, even
      after normalisation of PP to muscle volume. This finding likely plays an
      important role in the loss of mobility in old age.

PMID- 17530275
TI  - Mechanical efficiency during repetitive vertical jumping.
AB  - The purpose of this study was to compare mechanical efficiency between repeated
      static jumps (SJ), countermovement jumps (CMJ), drop jumps from 75% of maximum
      CMJ jump height (75DJ) and drop jumps from 125% of maximum CMJ height (125DJ).
      Subjects included eight jump-trained males. All subjects completed 30 continuous
      repetitions in the SJ, CMJ, 75DJ, and 125DJ. Oxygen consumption, peak force and
      center of mass displacement for each repetition during the four jumping patterns
      were measured. ME was calculated from a combination of force-time curves,
      displacement-time curves and lactate-corrected oxygen consumption values. In
      addition, muscle activity was recorded from the vastus medialis, vastus lateralis
      and biceps femoris using surface electromyography (EMG). 125DJ and 75DJ resulted
      in significantly (P < or = 0.05) greater ME in comparison to CMJ and SJ. CMJ
      resulted in significantly greater ME in comparison to SJ. In addition, braking
      phase muscle activity was significantly greater in 125DJ and 75DJ in comparison
      to CMJ. Negative work was significantly different between 125DJ, 75DJ and CMJ
      (125DJ > 75DJ > CMJ). There was a significant positive correlation (r = 0.68)
      between ME and negative work performed across 125DJ, 75DJ and CMJ. These findings
      suggest that stretch-shortening cycle movements, which include a strenuous
      braking phase combined with simultaneous high muscle activity, increase ME. This
      may be due to optimal muscle-tendon unit kinetics and usage of stored elastic
      energy.

PMID- 17530276
TI  - Four weeks one-leg training and high fat diet does not alter PPARalpha protein or
      mRNA expression in human skeletal muscle.
AB  - Fatty acid metabolism is influenced by training and diet with exercise training
      mediating this through activation of nuclear hormone receptor peroxisome
      proliferator-activated receptor alpha (PPARalpha) in skeletal muscle. This study
      investigated the effect of training and high fat or normal diet on PPARalpha
      expression in human skeletal muscle. Thirteen men trained one leg (T) four weeks
      (31.5 h in total), while the other leg (UT) served as control. During the 4 weeks
      six subjects consumed high fat (FAT) diet and seven subjects maintained a normal
      (CHO) diet. Biopsies were obtained from vastus lateralis muscle in both legs
      before and after training. After the biopsy, one-leg extension exercise was
      performed in random order with both legs 30 min at 95% of workload max. A
      training effect was evident as citrate synthase activity increased (P < 0.05) by
      15% in the trained, but not the control leg in both groups. During exercise
      respiratory exchange ratio was lower in FAT (0.86 +/- 0.01, 0.83 +/- 0.01, mean
      +/- SEM) than CHO (0.96 +/- 0.02, 0.94 +/- 0.03) and in UT than T legs,
      respectively. The PPARalpha protein (144 +/- 44, 104 +/- 28, 79 +/- 15, 79 +/-
      14, % of pre level) and PPARalpha mRNA (69 +/- [2, 2], 78 +/- [7, 6], 92 +/- [22,
      18], 106 +/- [21, 18], % of pre level, geometric mean +/- SEM) expression
      remained unchanged by diet and training in FAT (UT, T) and CHO (UT, T),
      respectively. After the training and diet CS, HAD, PPARalpha, UCP2, UCP3 and
      mFABP mRNA content remained unchanged, whereas GLUT4 mRNA was lower in both
      groups and LDHA mRNA was lower (P < 0.05) only in FAT. IN CONCLUSION: 4 weeks one
      leg knee extensor training did not affect PPARalpha protein or mRNA expression.
      Furthermore, higher fat oxidation during exercise after fat rich diet was not
      accompanied by an increased PPARalpha protein or mRNA expression after 4 weeks.

PMID- 17530277
TI  - Kinetic models of spike-timing dependent plasticity and their functional
      consequences in detecting correlations.
AB  - Spike-timing dependent plasticity (STDP) is a type of synaptic modification found
      relatively recently, but the underlying biophysical mechanisms are still unclear.
      Several models of STDP have been proposed, and differ by their implementation,
      and in particular how synaptic weights saturate to their minimal and maximal
      values. We analyze here kinetic models of transmitter-receptor interaction and
      derive a series of STDP models. In general, such kinetic models predict
      progressive saturation of the weights. Various forms can be obtained depending on
      the hypotheses made in the kinetic model, and these include a simple linear
      dependence on the value of the weight ("soft bounds"), mixed soft and abrupt
      saturation ("hard bound"), or more complex forms. We analyze in more detail
      simple soft-bound models of Hebbian and anti-Hebbian STDPs, in which nonlinear
      spike interactions (triplets) are taken into account. We show that Hebbian STDPs
      can be used to selectively potentiate synapses that are correlated in time, while
      anti-Hebbian STDPs depress correlated synapses, despite the presence of nonlinear
      spike interactions. This correlation detection enables neurons to develop a
      selectivity to correlated inputs. We also examine different versions of kinetics
      based STDP models and compare their sensitivity to correlations. We conclude that
      kinetic models generally predict soft-bound dynamics, and that such models seem
      ideal for detecting correlations among large numbers of inputs.

PMID- 17530278
TI  - Liver resection without hilus preparation and with selective intrahepatic hilus
      stapling for benign tumors and liver metastasis.
AB  - BACKGROUND: Nowadays, liver resection is a routine operative procedure in
      surgical centers, and strategies must be aimed at avoiding additional risk
      factors. Extrahepatic isolation of portal vein, hepatic artery and hepatic duct,
      as well as lymphadenectomy of the liver hilum are generally accepted steps of
      liver resection, even for metastatic and benign indications. Our primary aim was
      to analyze the feasibility, blood loss, blood transfusion requirements, incidence
      of complications, and outcome using the approach for intrahepatic
      devascularization leaving the extrahepatic hilus untouched. MATERIALS AND
      METHODS: Thirty-eight consecutive patients with resection for metastases and
      benign liver tumors were selected. After hilar examination, the extrahepatic
      structures remain intact, and during parenchyma dissection, the whole right or
      left or the appropriate bi-segmental pedicle is isolated intrahepatically and
      then transected using a stapler device. RESULTS: The used technique was feasible
      in all cases, and no intra- or postoperative surgical complications were
      observed. To date, no tumor recurrence was found in the hilum during the follow
      up period. CONCLUSION: The intrahepatic pedicle stapling technique appears to be
      feasible and safe in liver resection. Hilar dissection can, thus, be avoided in
      liver metastasis and benign liver tumors.

PMID- 17530279
TI  - Effectiveness of parathyroid-hormone measurement in detecting patients with
      multiple gland disease causing primary hyperparathyroidism.
AB  - BACKGROUND AND AIM: Intraoperative parathyroid hormone measurement (iPTH) has
      strengthened the successful use of minimal-invasive approaches in surgery of
      primary hyperparathyroidism (pHPT). The aim of the study was to evaluate the
      efficacy of iPTH monitoring in treating pHPT resulting from multiple gland
      disease. MATERIALS AND METHODS: In this retrospective study, 58 patients with
      pHPT underwent surgery (minimally invasive or open exploration) between January
      2003 and July 2005. iPTH levels were routinely measured at the start of
      anesthesia, in any case before skin incision, and 10 as well as 15 min after
      removal of abnormal gland(s). A drop in iPTH >50% after 10 min and >60% after 15
      min was considered adequate to prove the success of the removal of the abnormal
      gland(s). The removed tissue was examined histologically by immediate frozen
      section. RESULTS: A single gland disease was found in 51 (88%) cases, a multiple
      gland disease (double adenoma or hyperplasia) in 7 (12%) cases. In all cases of
      single adenoma, an adequate drop of iPTH was seen after removal of the pathologic
      gland. In contrast, in all cases with a second adenoma, an adequate drop in iPTH
      was detected only after removal of both adenoma/hyperplasia. Immediate sectioning
      was only helpful for identification of removed tissue, but was no help in
      deciding whether to search for an additional gland. The follow-up showed no late
      disease recurrence. CONCLUSION: The measurement of iPTH is an effective and safe
      means in treating single gland disease as well as multiple gland disease
      (adenoma/hyperplasia) causing pHPT and also allows a successful limited
      dissection via minimally invasive parathyroidectomy.

PMID- 17530280
TI  - Mucinous cystadenocarcinoma of the pancreas diagnosed in postpartum.
AB  - BACKGROUND: Cystic tumors of the pancreas are uncommon. They account for 10-15%
      of all pancreatic cystic masses and only 1% of pancreatic malignancies. Mucinous
      cystadenocarcinoma is the most frequent pancreatic cystadenocarcinoma and it is
      mainly seen in women, suggesting a sex hormone influence. Its presentation during
      pregnancy is infrequent and entails difficult diagnostic and therapeutic
      decisions. We report the case of a 31-year-old woman who presented a pancreatic
      cystadenocarcinoma 2 months after delivery. MATERIALS AND METHODS: A 31-year-old
      woman was referred to our service because of abdominal pain and mass. She had
      given birth to her first child 2 months previous. Abdominal ultrasound
      demonstrated a poorly circumscribed cystic mass in the left upper abdominal
      quadrant, and the computed tomography scan showed a multilocular cystic lesion
      located in the body of pancreas. There was no seric alteration of specific
      pancreatic enzymes or tumor markers. RESULTS: Laparoscopic examination showed a
      large cystic tumor (12 x 11 x 5.5 cm) in the pancreas involving the body and the
      tail. It extended to the spleen and was highly vascularized, precluding a minimal
      invasive resection. An open body-tail pancreatectomy and splenectomy was
      performed. The resection margins were free of tumor, and the histological study
      showed a mucinous pancreatic cystadenocarcinoma with mucin-producing columnar
      epithelium and associated papillae patterns, reminiscent of ovarian stroma.
      Immunohistochemical studies were negative for hormonal receptors. The patient had
      no post-surgical complications and was discharged home in 4 days. CONCLUSIONS:
      Cystic tumors of the pancreas are infrequent, and cancer of the pancreas during
      pregnancy is extremely rare. Insidious symptoms and bodily changes due to
      pregnancy may mask diagnosis. Aggressive surgery is currently the only chance of
      cure.

PMID- 17530281
TI  - Current concepts in transplant surgery: laparoscopic living donor of the kidney.
AB  - INTRODUCTION: Living donor kidney transplantation has emerged as an excellent
      alternative to cadaveric donation since, more than 50 years ago, the first live
      donor nephrectomy was successfully performed. OBJECTIVE: The basic idea of
      introducing laparoscopy in live donor nephrectomy was to obtain a potential
      reduction in incision-related morbidity with reduced pain and faster
      reconvalescence while providing at least the same level of operative security.
      This paper is focusing on technical aspects, outcome, results, and possible
      current concerns and advantages of laparoscopic living-related donor nephrectomy.
      CONCLUSION: According to our results and the results available in the literature,
      laparoscopic living donor nephrectomy is safe when performed with sufficient
      experience. Postoperative pain is less and recovery is significantly faster.

PMID- 17530282
TI  - Pseudoachalasia occurring after laparoscopic Nissen fundoplication and crural
      mesh repair.
AB  - BACKGROUND: Benign esophageal pseudoachalasia is a rare condition. DISCUSSION: We
      report the case of a 70-year-old man who complained of severe dysphagia after
      laparoscopic Nissen fundoplication and crural mesh repair performed for long
      standing gastroesophageal reflux disease. Severe dysphagia and nocturnal
      aspiration developed soon after the operation. A marked dilatation of the
      esophageal body and a manometric pattern resembling achalasia was documented.
      RESULTS: Endoscopic balloon dilatation was ineffective. Five months after the
      initial operation, the patient underwent revisional laparoscopic surgery that
      consisted of Nissen's wrap takedown, enlargement of the hiatus with partial
      resection of the mesh, Heller myotomy, and Dor fundoplication. After a 2-year
      follow-up, the patient is doing well and is free of symptoms.

PMID- 17530283
TI  - Hybrid procedures as a combined endovascular and open approach for pararenal and
      thoracoabdominal aortic pathologies.
AB  - OBJECTIVES: to report our experience with hybrid vascular procedures in patients
      with pararenal and thoracoabdominal aortic pathologies. METHODS: 68 patients were
      treated for thoracoabdominal aortic pathologies between October 1999 and February
      2004; 19 patients (16 men; mean age 68, range 40-79) with high risk for open
      thoracoabdominal repair were considered to be candidates for combined
      endovascular and open repair. Aortic pathologies included five thoracoabdominal
      Crawford I aneurysms, one postdissection expanding aneurysm, three symptomatic
      plaque ruptures (Crawford IV), five combined thoracic descending and infrarenal
      aneurysms with a healthy visceral segment, three juxtarenal or para-anastomotic
      aneurysms, and two patients with simultaneous open aortic arch replacement and a
      rendezvous maneuver for thoracic endografting. Commercially available endografts
      were implanted with standardized endovascular techniques after revascularization
      of visceral and renal arteries. RESULTS: Technical success was 95%. One patient
      developed a proximal type I endoleak after chronic expanding type B dissection
      and currently is waiting conversion. Nine patients underwent elective, five
      emergency and five urgent (within 24 h) repair. 17 operations were performed
      simultaneously, and 2 as a staged procedure. Postoperative complications include
      two retroperitoneal hemorrhages, and one patient required long-term ventilation
      with preexisting subglottic tracheal stenosis. Thirty-day mortality was 17% (one
      multiple organ failure, one secondary rupture after open aortic arch repair, one
      myocardial infarction). Paraplegia or acute renal failure were not observed.
      Total survival rate was to 83% with a mean follow-up of 30 months. CONCLUSIONS:
      Midterm results of combined endovascular and open procedures in the
      thoracoabdominal aorta are encouraging in selected high risk patients. Staged
      interventions may reduce morbidity.

PMID- 17530284
TI  - The effect of different temporary abdominal closure techniques on fascial wound
      healing and postoperative adhesions in experimental secondary peritonitis.
AB  - BACKGROUND: Secondary peritonitis causes considerable mortality and morbidity.
      New strategies have been introduced like relaparotomy and temporary abdominal
      closure in the management of such persistent intra-abdominal infections.
      MATERIALS AND METHODS: Rats were divided into five groups each having ten
      animals. After induction of peritonitis, relaparotomies were done, and the
      abdomen was closed by different temporary abdominal closure techniques. After
      performing two relaparotomies during a 48-h period, all fascias closed primarily
      and incisional tensile strengths, hydroxyproline contents, and adhesions were
      measured on the following seventh day. RESULTS: The median values of tensile
      strength and hydroxyproline concentrations were lowest in skin-only closure rats.
      Intraperitoneal adhesion scores were highest in Bogota bag closure group.
      CONCLUSION: Primary, Bogota bag, and polyprolene mesh closures seem to be safe in
      terms of early fascial wound healing. Although it is easy to perform, skin-only
      closure technique has deleterious effects on fascial wound healing probably due
      to fascial retraction. Interestingly, Bogota bag has caused increased
      intraperitoneal adhesion formation.

PMID- 17530285
TI  - Spinach SoHXK1 is a mitochondria-associated hexokinase.
AB  - Hexokinase, a hexose-phosphorylating enzyme, has emerged as a central enzyme in
      sugar-sensing processes. A few HXK isozymes have been identified in various plant
      species. These isozymes have been classified into two major groups; plastidic
      (type A) isozymes located in the plastid stroma and those containing a membrane
      anchor domain (type B) located mainly adjacent to the mitochondria, but also
      found in the nucleus. Of all the hexokinases that have been characterized to
      date, the only exception to this rule is a spinach type B HXK (SoHXK1) that, by
      means of subcellular fractionation, has been localized to the outer membrane of
      plastids. However, SoHXK1 has a membrane anchor domain that is almost identical
      to that of the other type B HXKs. To determine the localization of SoHXK1 enzyme
      by other means, we expressed SoHXK1::GFP fusion protein in tobacco and
      Arabidopsis protoplasts and compared its localization with that of the
      Arabidopsis AtHXK1::GFP fusion protein that shares a similar N-terminal membrane
      anchor domain. SoHXK1::GFP is localized adjacent to the mitochondria, similar to
      AtHXK1::GFP and all other previously examined type B HXKs. Proteomic analysis had
      previously identified AtHXK1 on the outside of the mitochondrial membrane. We,
      therefore, suggest that SoHXK1 enzyme is located adjacent to the mitochondria
      like the other type B HXKs that share the same N-terminal membrane anchor domain.

PMID- 17530286
TI  - Anciently duplicated Broad Complex exons have distinct temporal functions during
      tissue morphogenesis.
AB  - Broad Complex (BRC) is an essential ecdysone-pathway gene required for entry into
      and progression through metamorphosis in Drosophila melanogaster. Mutations of
      three BRC complementation groups cause numerous phenotypes, including a common
      suite of morphogenesis defects involving central nervous system (CNS), adult
      salivary glands (aSG), and male genitalia. These defects are phenocopied by the
      juvenile hormone mimic methoprene. Four BRC isoforms are produced by alternative
      splicing of a protein-binding BTB/POZ-encoding exon (BTBBRC) to one of four
      tandemly duplicated, DNA-binding zinc-finger-encoding exons (Z1BRC, Z2BRC, Z3BRC,
      Z4BRC). Highly conserved orthologs of BTBBRC and all four ZBRC were found among
      published cDNA sequences or genome databases from Diptera, Lepidoptera,
      Hymenoptera, and Coleoptera, indicating that BRC arose and underwent internal
      exon duplication before the split of holometabolous orders. Tramtrack subfamily
      members, abrupt, tramtrack, fruitless, longitudinals lacking (lola), and CG31666
      were characterized throughout Holometabola and used to root phylogenetic analyses
      of ZBRC exons, which revealed that the ZBRC clade includes Zabrupt. All four ZBRC
      domains, including Z4BRC, which has no known essential function, are evolving in
      a manner consistent with selective constraint. We used transgenic rescue to
      explore how different BRC isoforms contribute to shared tissue-morphogenesis
      functions. As predicted from earlier studies, the common CNS and aSG phenotypes
      were rescued by BRC-Z1 in rbp mutants, BRC-Z2 in br mutants, and BRC-Z3 in 2Bc
      mutants. However, the isoforms are required at two different developmental
      stages, with BRC-Z2 and -Z3 required earlier than BRC-Z1. The sequential action
      of BRC isoforms indicates subfunctionalization of duplicated ZBRC exons even when
      they contribute to common developmental processes.

PMID- 17530287
TI  - Microsatellite instability in Ewing tumor is not associated with loss of mismatch
      repair protein expression.
AB  - Only few clinical factors predict the prognosis of patients with Ewing tumors.
      Unfavorable outcome is associated with primary metastatic disease, age > 15
      years, tumor volume above 200 ml, and the histological response to chemotherapy.
      The aim of this study was to elucidate the prevalence and clinical impact of
      microsatellite instability (MSI) together with the relation between MSI and
      mismatch repair protein expression in Ewing tumors. DNA from 61 primary Ewing
      tumors and 11 Ewing tumor cell lines was extracted and microsatellite analysis
      for the detection of instability or loss of heterozygosity was performed for the
      five markers of the Bethesda panel BAT25, BAT26, D5S346, D2S123, and D17S250,
      which represents the established marker panel for the analysis of hereditary non
      polyposis colorectal carcinoma (HNPCC) patients. In addition, single nucleotide
      repeat regions of the two tumor genes BAX and transforming growth factor receptor
      II (TGFBR2) were also included. All of the 61 samples were suitable for LOH
      analysis and 55 for the determination of MSI-status. LOH of these microsatellite
      markers was detected in 9 of the 61 patients (14.8%). Over all, genetic
      instability, i.e. MSI and/or LOH, was detected in 17 tumors (27.9%). One out of
      the 11 tumor cell lines (STA ET1) was characterized by instability of all the
      five Bethesda markers, while from primary tumor samples, only one showed MSI in
      more than one microsatellite marker (D5S346 and D17S250, MSI-high). Eight of the
      fifty-five patients (14.5%) showed instability of one microsatellite locus (MSI
      low). No instability was detected in BAT26, D2S123, BAX and TGFBR2. There was no
      significant correlation between MSI and loss of expression of mismatch repair
      proteins MLH1, MSH2, or MSH6. The impairment of the p53 signaling pathway
      (expression of TP53 and/or MDM2 by immunohistochemistry) was significantly
      associated with reduced overall survival (15 of 49 patients (30.6%), P = 0.0410,
      log-rank test). We conclude that MSI is not prevalent in Ewing tumor and that the
      nature of instability differs from the form observed in colorectal carcinoma, the
      model tumor of MSI. This is documented by the different pattern of MSI (no BAT26
      instability) in Ewing tumors and the lack of a strict correlation between MSI
      high and loss of expression of MSH2, MSH6 and MLH1.

PMID- 17530288
TI  - Detection of Toxoplasma gondii in water by an immunomagnetic separation method
      targeting the sporocysts.
AB  - An immunomagnetic separation (IMS) method was developed to detect Toxoplasma
      gondii in fresh waters by using the monoclonal antibody 4B6 targeting the
      sporocyst wall of T. gondii, Hammondia hammondi, Hammondia heydorni, and Neospora
      caninum. Water concentrates obtained by filtering 10- to 20-l samples samples
      were spiked with Toxoplasma oocysts, sonicated to release the sporocysts, and
      analyzed by IMS-4B6. Mean sporocyst recoveries were 74.5 +/- 5.3% in drinking
      water, 30.6 +/- 2.4 and 37.1 +/- 3.2% in surface waters, and 81.6 +/- 2.1% in IMS
      buffer. Then, this IMS method was integrated in a multistep procedure (i.e.,
      filtration, IMS, immunofluorescence and autofluorescence) to detect Toxoplasma in
      unspiked and spiked water samples (10-30 l) of various qualities. Sporocyst
      recoveries ranged from 14.4 to 44.7% in drinking water samples spiked with 1-10
      oocysts/l, and from 17.8 to 32.5% in surface water samples spiked with 10
      oocysts/l. Sporocysts were not detected in 25 unspiked water samples. A sporocyst
      like structure was seen in one of these unspiked samples, but its coccidian
      nature could not be proved by three polymerase chain reaction (PCR) methods
      targeting sequences of coccidian small and large subunit rRNA genes and
      Toxoplasma repetitive elements. In conclusion, IMS-4B6 is relevant for the
      detection of Toxoplasma in water generating small concentrates (<1 ml). Due to
      4B6 cross-reactions, a PCR would be useful to further characterize coccidian
      sporocysts found microscopically.

PMID- 17530289
TI  - A locus on chromosome 10 influences C-reactive protein levels in two independent
      populations.
AB  - High sensitivity C-reactive protein (hsCRP) is an independent risk factor for
      cardiovascular disease, such as stroke or coronary artery disease. Genetic
      factors influence significantly the inter-individual variability of hsCRP. The
      aim of this study was to identify genomic regions influencing hsCRP levels. A
      genome scan was performed in two independent studies of Caucasian populations,
      namely 513 Western-European families ascertained for myocardial infarction (n =
      1,406) and 120 French-Canadian families diagnosed with hypertension (n = 758). In
      the myocardial infarction families, 31% of the inter-individual variation of
      hsCRP levels was explained by genetic factors (P = 0.0000015) and loci
      influencing hsCRP were identified on chromosomes 10 (at 141 cM) and 5 (at 150 cM)
      with multipoint LOD scores of 3.15 and 2.23, respectively. An additional
      suggestive signal was detected on chromosome 2 in subset analyses. A similar
      degree of heritability has been observed in a second independent population of
      French-Canadian hypertensive families for hsCRP (30%) and linkage results for
      chromosome 10 were confirmed with maximum LOD score of 2.7. We identified a
      chromosomal region in two independent populations which influences hsCRP in
      addition to several unique regions. This provides targets for the identification
      of genes involved in the regulation of hsCRP and the development and progression
      of vascular disease, including stroke.

PMID- 17530290
TI  - An extension of the weighted dissimilarity test to association study in families.
AB  - Association studies for complex diseases based on pedigree haplotype or genotype
      data have received increasing attention in the last few years. The similarity
      tests are appealing for these studies because they take into account of the DNA
      structure, but they have blind areas on which significant association can not be
      detected. Recently, we developed a dissimilarity method for this problem based on
      independent haplotype data, which eliminates the blind areas of the existing
      methods. As DNA collected on families are common in practice, and the data are
      either of the form of genotype or haplotype. Here we extend our method for
      association study to data on families. It can be used to evaluate different
      designs in terms of power. Simulation studies confirmed that the extended method
      improves the type I error rate and power. Applying this method to the Genetic
      Analysis Workshop 14 alcoholism data, we find that markers rs716581, rs1017418,
      rs1332184 and rs1943418 on chromosomes 1, 2, 9 and 18 yield strong signal (with P
      value 0.001 or lower) for association with alcoholism. Our work can serve as a
      guide in the design of association studies in families.

PMID- 17530291
TI  - Amphibian lipid levels at metamorphosis correlate to post-metamorphic terrestrial
      survival.
AB  - In organisms that have complex life cycles, factors in the larval environment may
      affect both larval and adult traits. For amphibians, the postmetamorphic
      transition from the aquatic environment to terrestrial habitat may be a period of
      high juvenile mortality. We hypothesized that lipid stores at metamorphosis may
      affect an animal's success during this critical transition period. We examined
      variation in total lipid levels among years and sites in recently metamorphosed
      individuals of two pond-breeding salamander species, the marbled salamander
      (Ambystoma opacum) and the mole salamander (A. talpoideum), with limited data for
      one anuran species (southern leopard frog, Rana sphenocephala). Lipid levels were
      allometrically related to body size and ranged from 1.9 to 23.8% of body dry
      mass. The two salamander species differed in lipid allocation patterns, with A.
      opacum apportioning a higher percentage of total lipid reserves into fat bodies
      than A. talpoideum. Species differences in lipid allocation patterns may
      primarily reflect that large metamorphs will mature as one-year olds, and,
      regardless of species, will alter lipid compartmentalization accordingly. We used
      mark-recapture data obtained at drift fences encircling breeding ponds for 13 A.
      opacum cohorts to estimate the proportion of postmetamorphic individuals that
      survived to breed (age 1-4) and the mean age at first reproduction. Regression
      models indicated that size-corrected lipid level at metamorphosis (i.e., lipid
      residuals), and to a lesser extent rainfall following metamorphosis, was
      positively related to adult survival. Snout-vent length at metamorphosis was
      negatively related to age at first reproduction. We suggest that lipid stores at
      metamorphosis are vital to juvenile survival in the months following the
      transition from aquatic to terrestrial habitat, and that a trade-off shaped by
      postmetamorphic selection in the terrestrial habitat exists between allocation to
      energy stores versus structural growth in the larval environment.

PMID- 17530292
TI  - Resource complementation and the response of an insect herbivore to habitat area
      and fragmentation.
AB  - Few studies have disentangled the effects of the area and fragmentation of a
      focal habitat type on species that use multiple habitat types within a landscape.
      We experimentally investigated the effects of habitat area, habitat
      fragmentation, and matrix composition on the movement and distribution of
      Melanoplus femurrubrum. Adults of this grasshopper feed preferentially on
      grasses, but oviposit almost exclusively in soil dominated by forbs. We compared
      population densities among plots that were made to vary in the area and
      fragmentation of clover habitat and composition of the matrix (grass or bare
      ground) within which clover habitat was embedded. In addition, a mark-recapture
      survey was conducted to examine effects of habitat area, fragmentation, and
      matrix composition on loss of individuals from a plot's clover habitat and
      movement between clover subplots within plots. Overall densities of adult M.
      femurrubrum (averaged over clover and matrix) were 2.2x higher in plots where the
      matrix was composed of grass as compared to bare ground, and 1.8x higher in plots
      with 64 compared to 16 m(2) of clover habitat. Overall densities of nymphs were
      also positively influenced by greater clover area, but were unaffected by matrix
      composition. Within focal clover habitat embedded in grass matrix, adult
      densities were 2.1x higher in small clover subplots than large clover subplots.
      We conclude that the grass matrix had a positive effect on adult densities, but
      not nymph densities, because grass and forb-dominated habitats likely provide
      complementary resources only for adults. The aggregation of adults on small
      clover subplots within grass matrix was mainly attributed to a greater rate of
      emigration loss per unit area. In addition, this study emphasizes that a species'
      response to changes in the area of a focal habitat type can depend significantly
      on the availability of complementary resources in the surrounding landscape.

PMID- 17530293
TI  - Invading rainbow trout usurp a terrestrial prey subsidy from native charr and
      reduce their growth and abundance.
AB  - Movements of prey organisms across ecosystem boundaries often subsidize consumer
      populations in adjacent habitats. Human disturbances such as habitat degradation
      or non-native species invasions may alter the characteristics or fate of these
      prey subsidies, but few studies have measured the direct effects of this
      disruption on the growth and local abundance of predators in recipient habitats.
      Here we present evidence, obtained from a combined experimental and comparative
      study in northern Japan, that an invading stream fish usurped the flux of
      allochthonous prey to a native fish, consequently altering the diet and reducing
      the growth and abundance of the native species. A large-scale field experiment
      showed that excluding terrestrial invertebrates that fell into the stream with a
      mesh greenhouse reduced terrestrial prey in diets of native Dolly Varden charr
      (Salvelinus malma) by 46-70%, and reduced their growth by 25% over six weeks.
      However, when nonnative rainbow trout (Oncorhynchus mykiss) were introduced, they
      monopolized these prey and caused an even greater reduction of terrestrial prey
      in charr diets of 82-93%, and reduced charr growth by 31% over the same period.
      Adding both greenhouse and rainbow trout treatments together produced similar
      results to adding either alone. Results from a comparative field study of six
      other stream sites in the region corroborated the experimental findings, showing
      that at invaded sites rainbow trout usurped the terrestrial prey subsidy, causing
      a more than 75% decrease in the biomass of terrestrial invertebrates in Dolly
      Varden diets and forcing them to shift their foraging to insects on the stream
      bottom. Moreover, at sites with even low densities of rainbow trout, biomass of
      Dolly Varden was more than 75% lower than at sites without rainbow trout.
      Disruption of resource fluxes between habitats may be a common, but unidentified,
      consequence of invasions, and an additional mechanism contributing to the loss of
      native species.

PMID- 17530294
TI  - Natal location influences movement and survival of a spatially structured
      population of snail kites.
AB  - Despite the accepted importance of the need to better understand how natal
      location affects movement decisions and survival of animals, robust estimates of
      movement and survival in relation to the natal location are lacking. Our study
      focuses on movement and survival related to the natal location of snail kites in
      Florida and shows that kites, in addition to exhibiting a high level of site
      tenacity to breeding regions, also exhibit particular attraction to their natal
      region. More specifically, we found that estimates of movement from post
      dispersal regions were greater toward natal regions than toward non-natal regions
      (differences were significant for three of four regions). We also found that
      estimates of natal philopatry were greater than estimates of philopatry to non
      natal regions (differences were statistically significant for two of four
      regions). A previous study indicated an effect of natal region on juvenile
      survival; in this study, we show an effect of natal region on adult survival.
      Estimates of adult survival varied among kites that were hatched in different
      regions. Adults experienced mortality rates characteristic of the region occupied
      at the time when survival was measured, but because there is a greater
      probability that kites will return to their natal region than to any other
      regions, their survival was ultimately influenced by their natal region. In most
      years, kites hatched in southern regions had greater survival probabilities than
      did kites hatched in northern regions. However, during a multiregional drought,
      one of the northern regions served as a refuge from drought, and during this
      perturbation, survival was greater for birds hatched in the north. Our study
      shows that natal location may be important in influencing the ecological dynamics
      of kites but also highlights the importance of considering temporal variation in
      habitat conditions of spatially structured systems when attempting to evaluate
      the conservation value of habitats.

PMID- 17530295
TI  - Probiotics prophylaxis in children with persistent primary vesicoureteral reflux.
AB  - Probiotics, beneficial living microorganisms, have been proven to be effective in
      preventing gastrointestinal infections, but their effect in preventing urinary
      tract infection (UTI) is inconclusive. A prospective randomized controlled study
      was done to compare the preventive effect of probiotics with conventional
      antibiotics in children with persistent primary vesicoureteral reflux (VUR). One
      hundred twenty children who had had persistent primary VUR after antibiotic
      prophylaxis for 1 year were randomly allocated into a probiotics (Lactobacillus
      acidophilus 10(8) CFU/g 1 g b.i.d., n = 60) or an antibiotics
      (trimethoprim/sulfamethoxazole 2/10 mg/kg h.s., n = 60) prophylaxis group during
      the second year of follow-up. The incidence of recurrent UTI was 18.3% (11/60) in
      the probiotics group, which was not different from 21.6%(13/60) in the antibiotic
      group (P = 0.926). The causative organisms of recurrent UTI were not
      significantly different between the two groups (P = 0.938). Even after
      stratification by VUR grade, age, gender, phimosis, voiding dysfunction and renal
      scar, the incidence of recurrent UTI did not differ significantly between the two
      groups (P > 0.05). The development of new renal scar was not significantly
      different between the two groups (P > 0.05). In conclusion, probiotics
      prophylaxis was as effective as antibiotic prophylaxis in children with
      persistent primary VUR.

PMID- 17530296
TI  - Renin-angiotensin axis blockade reduces proteinuria in presymptomatic patients
      with familial FSGS.
AB  - Familial and genetic forms of focal segmental glomerulosclerosis (FSGS) are
      associated with six different mutations in genes affecting the podocyte (NPHS2,
      ACTN4, CD2AP, WT1, TRPC6, and PLCE1). Immunosuppressive agents are often
      unsuccessful in treating this condition. Data regarding the efficacy of
      renoprotection through blockage of the renin-angiotensin axis is lacking. We
      describe three children from two different families with familial FSGS in whom
      partial to complete remission of proteinuria was attained through early blockade
      of the renin-angiotensin axis. In addition, there was no deterioration of renal
      function. We speculate that presymptomatic patients with normal renal function
      who have genetic or familial FSGS may benefit from early blockade of the renin
      angiotensin axis and that this may also prevent progressive renal disease.

PMID- 17530297
TI  - Streptococcal exotoxin B increases interleukin-6, tumor necrosis factor alpha,
      interleukin-8 and transforming growth factor beta-1 in leukocytes.
AB  - Previous reports have shown the presence of streptococcal erythrogenic exotoxin
      type B (ETB), leukocyte infiltration, interleukin-8 (IL-8), transforming growth
      factor-beta (TGF-beta) and glomerular proliferation in renal biopsies from
      patients with acute post-streptococcal glomerulonephritis (APSGN). In addition,
      increased levels of plasma interleukin-6 (IL-6) and tumor necrosis factor alpha
      (TNFalpha), and urinary IL-6, have also been reported in this disease. To
      determine the effect of streptococcal proteins on leukocyte proliferation and
      leukocyte production of IL-6, TNFalpha, IL-8 and TGF-beta1, we cultured human
      mononuclear leukocytes with ETB or ETB precursor (ETBP). After 24 h, 48 h and 96
      h, culture supernatants were assessed for cytokines by enzyme-linked
      immunosorbent assay (ELISA), and for leukocyte proliferation by a monoclonal
      antibody anti-proliferating cellular nuclear antigen (PCNA). A significant
      increase in all cytokines was found in ETB- or ETBP-treated cultures when
      compared with controls. A polyclonal anti-ETB antibody diminished the cytokine
      stimulatory effect of ETB. An increased number of PCNA-positive cells was
      observed in ETB or ETBP treated cultures at 48 h and 96 h. Cytokine production
      and proliferation were not correlated. The stimulatory effect of streptococcal
      exotoxin B on leukocyte cytokine production may be relevant in renal tissue
      during the course of APSGN.

PMID- 17530298
TI  - Treating severe Henoch-Schonlein and IgA nephritis with plasmapheresis alone.
AB  - The aim of our study was to determine the outcome of children with severe Henoch
      Schonlein nephritis (HSN) and immunoglobulin A (IgA) nephritis (IgAN) treated
      with early plasmapheresis alone. Children with acute renal impairment, heavy
      proteinuria or both and histology greater than grade 3 were treated with early
      plasmapheresis alone. Glomerular filtration rate (GFR) estimated from plasma
      creatinine (eGFR), urine albumin:creatinine ratio (UA/UC) and blood pressure 2
      weeks after treatment and were measured at the last follow-up. Sixteen children
      (14 HSN, 2 IgAN) had a mean eGFR of 56 (17-136) ml/min per 1.73 m2 and UA/UC of
      590 (12-1,379) mg/mmol. Fifteen were referred at presentation and one after 2
      months, and all commenced plasmapheresis within 6 (2-13) days. All had at least
      nine exchanges of 90 ml/kg over 2 weeks. At 2 weeks, the eGFR had increased by 51
      (95% CI 34-68; P=0.002), and the UA/UC fell by 457 (95% CI 241-673; P=0.0001). At
      last review after 4 (1-7.5) years, the late-referred child had required a renal
      transplant but the other 15 had normal eGFRs (98-142), did not require
      hypotensive medication, and had normal or minimally elevated UA/UC (maximum 42).
      Children with severe HSN and IgAN recover well if treated with plasmapheresis
      alone without the need for immunosuppressive therapy. A randomised trial is
      needed.

PMID- 17530299
TI  - Use of rhGH in children with chronic kidney disease: lessons from NAPRTCS.
AB  - We evaluated the utilization and potential benefits of recombinant human growth
      hormone (rhGH) in children with chronic kidney disease (CKD) and following renal
      transplantation in a large patient cohort. We queried the chronic renal
      insufficiency (CRI), dialysis, and transplant registries of the North American
      Pediatric Renal Trials and Collaborative Studies (NAPRTCS) to characterize the
      frequency of rhGH utilization, factors related to its usage, and the relationship
      between rhGH usage and catch-up growth. Data from 6,505, 5,122, and 4,478 CRI,
      dialysis, and transplant patients, respectively, was evaluated. Percentage
      utilization of rhGH 2 years after registry entry was 22%, 33%, and 3% in children
      with a height standard deviation score (SDS)<-1 and age<17 years (termed
      candidate group) in CRI, dialysis, and transplant patients, respectively.
      Multivariate logistic regression analysis showed that the likelihood of using
      rhGH was significantly correlated with age, gender, geographical region of
      residence and height category within the candidate group (p<0.01). The use of
      rhGH was associated with catch-up growth in 27%, 11%, and 25% of candidate CRI,
      dialysis, and transplant patients, respectively. In the candidate group,
      percentage catch-up growth was highest in children who were Tanner stage 1-2, who
      comprised 19.4%, 7.1%, and 25.5% of the CRI, dialysis, and transplant patients,
      respectively. Using multiple regression analysis, the estimated impact of rhGH on
      final adult height (age>19 years) was 0.80, 0.50, and 0.19 SDS, in CRI, dialysis,
      and transplant patients, respectively. Thus, rhGH can improve height gain in some
      children with CKD. The use of rhGH appears to be most effective in prepubertal
      children with CRI.

PMID- 17530300
TI  - [Evidence for laser acupuncture in cases of orthopedic diseases : a systematic
      review].
AB  - BACKGROUND AND OBJECTIVES: The aim of this review is to evaluate the evidence for
      laser acupuncture in selected orthopaedic diseases. MATERIAL AND METHODS:
      Randomized controlled studies, meta-analyses and systematic reviews were
      identified by a systematic search strategy in Medline and the Cochrane library.
      The studies were evaluated using the quality criteria of the Oxford Centre of
      Evidence Based Medicine. RESULTS: For the selected orthopedic diseases (medial
      and lateral epicondylitis, myofascial pain syndrome of the neck, back and
      shoulder and osteoarthritis), meta-analyses, systematic reviews and eight
      randomized controlled studies were found. All other published studies used laser
      therapy without consideration of classical acupuncture points. All studies had
      significant drawbacks in methodological quality and the number of patients
      included. In more recent trials, improvement towards higher methodological
      quality was obvious. Although current evidence is equivocal, positive effects can
      be assumed in myofascial pain syndromes of the neck, back and shoulder. Laser
      acupuncture is advantageous in terms of side effects compared to classical
      acupuncture techniques. CONCLUSION: Better, well designed randomized studies with
      higher power are mandatory in orthopedic diseases.

PMID- 17530301
TI  - Livestock production system management responses to thermal challenges.
AB  - The adaptive capabilities of animals and livestock production systems have been
      emphasized in this report. Biometeorology has a key role in rational management
      to meet the challenges of thermal environments. While the focus is primarily on
      cattle in warm or hot climates, the importance of dynamic animal responses to
      environmental challenges applies to all species and climates. Methods used to
      mitigate environmental challenges focus on heat loss/heat production balance.
      Under cold stress, reduction of heat loss is the key. Under heat stress,
      reduction of heat load or increasing heat loss are the primary management tools,
      although heat-tolerant animals are also available. In general, livestock with
      health problems and the most productive animals (e.g., highest growth rate or
      milk production) are at greatest risk of heat stress, thereby requiring the most
      attention. Risk management, by considering perceived thermal challenges, then
      assessing the potential consequences and acting accordingly, will reduce the
      impact of such challenges. Appropriate actions include: shade, sprinkling, air
      movement, or active cooling. Summarizing, the most important element of proactive
      environmental management to reduce risk is preparation: be informed, develop a
      strategic plan, observe and recognize animals in distress, and take appropriate
      tactical action.

PMID- 17530302
TI  - Endocrine symptom assessment in women with breast cancer: what a simple "yes"
      means.
AB  - GOALS OF WORK: To investigate the self-reported symptoms related to endocrine
      therapy in women with early or advanced breast cancer and the impact of these
      symptoms on quality of life (QL) indicators. MATERIALS AND METHODS: Symptom
      occurrence was assessed by the Checklist for Patients on Endocrine Therapy (C
      PET) and symptom intensity was assessed by linear analogue self-assessment (LASA)
      indicators. Patients also responded to global LASA indicators for physical well
      being, mood, coping effort and treatment burden. Associations between symptoms
      and these indicators were analysed by linear regression models. MAIN RESULTS:
      Among 373 women, the distribution of symptom intensity showed considerable
      variation in patients reporting a symptom as present. Even though patients
      recorded a symptom as absent, some patients reported having experienced that
      symptom when responding to symptom intensity, as seen for decreased sex drive,
      tiredness and vaginal dryness. Six of 13 symptoms and lower age had a detrimental
      impact on the global indicators, particularly tiredness and irritability.
      CONCLUSIONS: Patients' experience of endocrine symptoms needs to be considered
      both in patient care and research, when interpreting the association between
      symptoms and QL.

PMID- 17530303
TI  - Gene expression profiling of a Zn-tolerant and a Zn-sensitive Suillus luteus
      isolate exposed to increased external zinc concentrations.
AB  - Complementary DNA (cDNA)-amplified fragment-length polymorphism (AFLP) was
      applied to analyze transcript profiles of a Zn-tolerant and a Zn-sensitive
      isolate of the ectomycorrhizal basidiomycete Suillus luteus, both cultured with
      and without increased external zinc concentrations. From the obtained transcript
      profiles that covered approximately 2% of the total expected complement of genes
      in S. luteus, 144 nonredundant, differentially expressed transcript-derived
      fragments (TDFs), falling in different classes of expression pattern, were
      isolated and sequenced. Thirty-six of the represented genes showed homology to
      function-known genes, whereas 6 matched unknown protein coding sequences, and 102
      were possibly novel. Although relatively few TDFs were found to be responsive to
      the different zinc treatments, their modulated expression levels may suggest a
      different transcriptional response to zinc treatments in both isolates. Among the
      identified genes that could be related to heavy-metal detoxification or the
      tolerance trait were genes encoding for homologues of a heat-shock protein, a
      putative metal transporter, a hydrophobin, and several proteins involved in
      ubiquitin-dependent proteolysis.

PMID- 17530304
TI  - Benzothiazole bipyridine complexes of ruthenium(II) with cytotoxic activity.
AB  - A series of benzothiazole-substituted trisbipyridine ruthenium(II) analogues
      {[Ru(bpy)(2)(4,5'-bbtb)](2+), [Ru(bpy)(2)(5,5'-bbtb)](2+) and [Ru(bpy)(2)(5
      mbtb)](2+) [bpy is 2,2'-bipyridine, bbtb is bis(benzothiazol-2-yl)-2,2'
      bipyridine, 5-mbtb is 5-(benzothiazol-2-yl),5'-methyl-2,2'-bipyridine]} have been
      prepared and compared with the complex [Ru(bpy)(2)(4,4'-bbtb)](2+) reported
      previously. From the UV-vis spectral studies, substitution at the 5-position of
      the bpy causes the ligand-centred transitions to occur at considerably lower
      energy than for those with the functionality at the 4-position, while at the same
      time causing the emission to be effectively quenched. However, substitution at
      the 4-position causes the metal-to-ligand charge transfer to occur at lower
      energies. Fluorescent intercalator displacement studies indicate that the doubly
      substituted complexes displace ethidium bromide from a range of oligonucleotides,
      with the greater preference shown for bulge and hairpin sequences by the Lambda
      enantiomer. Since the complexes only show small variation in the UV-vis spectra
      on the introduction of calf thymus DNA and a small increase in fluorescence they
      do not appear to be intercalators, but appear to associate within one of the
      grooves. All of the reported bisbenzothiazole complexes show reasonable
      cytotoxicity against a range of human cancer cell lines.

PMID- 17530305
TI  - Pulpal responses after application of current adhesive systems to deep cavities.
AB  - The aim of the present study was to evaluate comparatively the pulpal tissue
      reactions of four adhesive systems placed in experimental cavities of healthy
      dog's teeth. Class V cavities with a mean value of remaining dentin thickness
      (RDT) ranging between 0.55 +/- 0.30-0.68 +/- 0.38 mm were prepared. The cavities
      were treated with the following adhesive systems: Etch and Prime 3.0 (EP), Single
      Bond (SB), Clearfil SE Bond (CSE), and Prompt L-Pop (PLP). The pulpal tissue
      responses to dentin adhesives were assessed histopathologically at postoperative
      periods of 7, 21, and 65 days, and the results were subjected to statistical
      analysis. A significantly greater adverse inflammatory response was observed with
      the materials EP and PLP, while a significantly lesser degree of disorganization
      in the odontoblastic zone was found with the materials SB and CSE, in the
      postoperative period of 65 days. In addition, a thicker predentin zone was
      observed where SB material was applied. Application of the selected adhesive
      systems to non-exposed cavities, with an RDT, which ranged between the above
      mentioned rates, was correlated with slight to moderate inflammation and
      odontoblast reduction depending on the materials used as well as upon the RDT.

PMID- 17530306
TI  - Secular trends in severe renal failure associated with the use of new
      antimicrobial agents in critically ill surgical patients.
AB  - Randomized controlled trials conducted since 2000 have shown that new
      antibacterial and antifungal agents may reduce the frequency of kidney injury in
      selected groups of critically ill patients, yet it is unclear whether these
      benefits translate to the clinical setting. The aim of the present study was to
      evaluate longitudinally the successive routine implementation of new
      antimicrobial agents (caspofungin, voriconazole, linezolid) after February 2002
      and the association of these agents with the frequency of mechanical renal
      replacement therapy in postsurgical critically ill patients at risk of severe
      kidney failure. A retrospective, observational cohort study was performed using
      data collected prospectively from 1 March 1993 through 28 February 2005. A cohort
      of 2,123 consecutive cases who required intensive care therapy for more than 2
      days was analysed. A statistically significant decrease in the frequency of renal
      replacement therapy was observed in the later years of the study. After
      adjustment for relevant covariates, treatment with new antimicrobial agents after
      February 2002 was identified as an independent factor linked with a reduced risk
      of severe kidney failure (odds ratio 0.244; 95% confidence interval 0.136-0.439).
      Thus, the implementation of new antimicrobial agents with reduced or no
      nephrotoxicity into routine care of critically ill surgical patients is
      associated with a reduced need for renal replacement therapy.

PMID- 17530307
TI  - Drug resistance in pulmonary tuberculosis in Turkey.

PMID- 17530308
TI  - BDNF contributes to animal model neuropathic pain after peripheral nerve
      transection.
AB  - The outcome of peripheral nerve injury is often impaired by neuropathic pain,
      which is resistant to most analgesics and presents a serious clinical problem.
      The mechanisms underlying post-traumatic neuropathic pain remain unclear, but
      they are likely associated with the regeneration processes. Brain-derived
      neurotrophic factor (BDNF) is known to enhance peripheral nerve regeneration and
      is also considered to be an endogenous modulator of nociceptive responses
      following spinal cord lesion. The aim of this work was to examine the local
      effect of BDNF in a neuropathic pain model. Sciatic nerves of adult male rats
      were transected and supplied with connective tissue chambers filled with (1)
      fibrin only, (2) fibrin with BDNF, or (3) fibrin with antibodies against BDNF. In
      control animals the nerve was transected and no chamber was applied. During
      follow-up, autotomy behavior was assessed. Seven weeks after the operation, the
      number of surviving and regenerating neurons in dorsal root ganglia was counted
      and the neuroma incidence was examined. We found that local inactivation of BDNF
      decreased the incidence as well as severity of autotomy and neuroma formation,
      but did not influence neuron regeneration into the chambers. These results
      indicate that BDNF plays a locally crucial role in neuropathic pain development
      after peripheral nerve injury.

PMID- 17530309
TI  - Economic evaluation of the treatment of type 2 diabetes with insulin glargine
      based on the LAPTOP trial.
AB  - In the LAPTOP trial, combination therapy with once-daily insulin glargine + oral
      antidiabetic agents glimepiride and metformin (BOT) was compared to twice-daily
      premixed insulin (CT). BOT was safer and more effective than CT. Cost analysis of
      both regimens were compared over a 1-year period. Analyses were performed from
      the perspective of the German statutory health insurance. Costs per patient per
      year were on average 236euro lower for BOT than for CT therapy. Economic
      advantage for BOT was robust to variation of expenses within a range of at least
      +/-20%. Insulin utilisation and prices were the major cost drivers, followed by
      costs associated with monitoring of blood glucose levels. Cost analysis of the
      LAPTOP trial suggest that BOT is more cost effective alternative to CT.

PMID- 17530310
TI  - A mathematical model for bone tissue regeneration inside a specific type of
      scaffold.
AB  - Bone tissue regeneration using scaffolds is receiving an increasing interest in
      orthopedic surgery and tissue engineering applications. In this study, we present
      the geometrical characterization of a specific family of scaffolds based on a
      face cubic centered (FCC) arrangement of empty pores leading to analytical
      formulae of porosity and specific surface. The effective behavior of those
      scaffolds, in terms of mechanical properties and permeability, is evaluated
      through the asymptotic homogenization theory applied to a representative volume
      element identified with the unit cell FCC. Bone growth into the scaffold is
      estimated by means of a phenomenological model that considers a macroscopic
      effective stress as the mechanical stimulus that regulates bone formation. Cell
      migration within the scaffold is modeled as a diffusion process based on Fick's
      law which allows us to estimate the cell invasion into the scaffold
      microstructure. The proposed model considers that bone growth velocity is
      proportional to the concentration of cells and regulated by the mechanical
      stimulus. This model allows us to explore what happens within the scaffold, the
      surrounding bone and their interaction. The mathematical model has been
      numerically implemented and qualitatively compared with previous experimental
      results found in the literature for a scaffold implanted in the femoral condyle
      of a rabbit. Specifically, the model predicts around 19 and 23% of bone
      regeneration for non-grafted and grafted scaffolds, respectively, both with an
      initial porosity of 76%.

PMID- 17530311
TI  - Effectiveness of an on-call counselor at increasing smoking treatment.
AB  - BACKGROUND: Smoking cessation programs are very effective, but little is known
      about how to get smokers to attend these programs. OBJECTIVE: To evaluate whether
      an "on-call" counselor increased smoking cessation program referrals and
      attendance. DESIGN: We randomly assigned 1 of 2 primary care teams at the
      Sepulveda VA Ambulatory Care Center to intervention and the other to usual care.
      The intervention team had access to an on-call counselor who provided counseling
      and care coordination. Social marketing efforts included educational outreach,
      provider feedback, and financial incentives. MEASUREMENTS: Baseline telephone
      interviews with a sample of 482 smokers were conducted, covering smoking history,
      health status, and smoking cessation treatments. Follow-up surveys were conducted
      at mid-intervention (n = 251) and post-intervention (n = 251). RESULTS: Two
      hundred ninety-six patients were referred to the on-call counselor, who counseled
      each patient in person and provided follow-up calls. The counselor referred 45%
      to the on-site program, and 27% to telephone counseling; of these, half followed
      through on the referral; 28% declined referral. Patients on the intervention team
      were more likely to report being counseled about smoking (68% vs 56%; odds ratio
      [OR] 1.7, CI 1.0-2.9) and referred to a cessation program (38% vs 23%; OR 2.1, CI
      1.2-3.6); having attended the program (11% vs 4%; OR 3.6, CI 1.2-10.5); and
      receiving a prescription for bupropion (17% vs 8%) (OR 2.3, CI 1.1-5.1). The
      effect was not sustained after the case management period. CONCLUSIONS: Having
      access to an on-call counselor with case management increased rates of smoking
      cessation counseling, referral, and treatment. The intervention could be
      reproduced by other health care systems.

PMID- 17530312
TI  - Abused women disclose partner interference with health care: an unrecognized form
      of battering.
AB  - BACKGROUND: Some providers observe that partners interfere with health care
      visits or treatment. There are no systematic investigations of the prevalence of
      or circumstances surrounding partner interference with health care and intimate
      partner violence (IPV). OBJECTIVE: To determine whether abused women report
      partner interference with their health care and to describe the co-occurring risk
      factors and health impact of such interference. DESIGN: A written survey of women
      attending health care clinics across 5 different medical departments (e.g.,
      emergency, primary care, obstetrics-gynecology, pediatrics, addiction recovery)
      housed in 8 hospital and clinic sites in Metropolitan Boston. PARTICIPANTS: Women
      outpatients (N = 2,027) ranging in age, 59% White, 38% married, 22.6% born
      outside the U.S. MEASUREMENT: Questions from the Severity of Violence and Abuse
      Assessment Scale, the SF-36, and questions about demographics. RESULTS: One in 20
      women outpatients (4.6%) reported that their partners prevented them from seeking
      or interfered with health care. Among women with past-year physical abuse (n =
      276), 17% reported that a partner interfered with their health care in contrast
      to 2% of women without abuse (adjusted odds ratios [OR] = 7.5). Further adjusted
      risk markers for partner interference included having less than a high school
      education (OR = 3.2), being born outside the U.S. (OR = 2.0), and visiting the
      clinic with a man attending (OR = 1.9). Partner interference raised the odds of
      women having poor health (OR = 1.8). CONCLUSIONS: Partner interference with
      health care is a significant problem for women who are in abusive relationships
      and poses an obstacle to health care. Health care providers should be alert to
      signs of patient noncompliance or missed appointments as stemming from abusive
      partner control tactics.

PMID- 17530313
TI  - Anatomical and physiological evidence for polarisation vision in the nocturnal
      bee Megalopta genalis.
AB  - The presence of a specialised dorsal rim area with an ability to detect the e
      vector orientation of polarised light is shown for the first time in a nocturnal
      hymenopteran. The dorsal rim area of the halictid bee Megalopta genalis features
      a number of characteristic anatomical specialisations including an increased
      rhabdom diameter and a lack of primary screening pigments. Optically, these
      specialisations result in wide spatial receptive fields (Deltarho = 14 degrees ),
      a common adaptation found in the dorsal rim areas of insects used to filter out
      interfering effects (i.e. clouds) from the sky. In this specialised eye region
      all nine photoreceptors contribute their microvilli to the entire length of the
      ommatidia. These orthogonally directed microvilli are anatomically arranged in an
      almost linear, anterior-posterior orientation. Intracellular recordings within
      the dorsal rim area show very high polarisation sensitivity and a sensitivity
      peak within the ultraviolet part of the spectrum.

PMID- 17530314
TI  - Alpha-lipoic acid increases cardiac glucose oxidation independent of AMP
      activated protein kinase in isolated working rat hearts.
AB  - Alpha-lipoic acid (ALA) is a naturally occurring enantiomer of lipoic acid and is
      a cofactor of key metabolic enzyme complexes catalyzing the decarboxylation of
      alpha-keto acids. It was recently shown that ALA increases insulin sensitivity by
      activating AMP-activated protein kinase (AMPK) in skeletal muscle. Also,
      administration of ALA to obese rats increases insulin-stimulated glucose uptake
      in the whole body. We investigated the metabolic effects of ALA on isolated
      working rat hearts. ALA (500 microM) stimulated glucose oxidation (157+/-31
      nmol.dry wt(-1).min(-1) in control vs 315+/-63 nmol.dry wt(-1).min(-1) in ALA
      treated, p<0.05) without affecting glycolysis, lactate oxidation, or palmitate
      oxidation. Cardiac work was not affected by ALA treatment. The effect of ALA on
      glucose oxidation was not associated with an activation of AMPK. AMPK activity
      was 190+/-14 pmol.mg protein(-1).min(-1) in control vs 190+/-16 pmol.mg protein(
      1).min(-1) in ALA-treated hearts. This study shows that ALA stimulates glucose
      oxidation in isolated working rat hearts independent of AMPK activation. The
      beneficial effects of ALA treatment in diabetic patients may be at least in part
      related to its effect on glucose metabolism.

PMID- 17530315
TI  - Survival pathways in hypertrophy and heart failure: the gp130-STAT3 axis.
AB  - Circulating levels of interleukin (IL)-6 and related cytokines are elevated in
      patients with congestive heart failure and after myocardial infarction. Serum IL
      6 concentrations are related to decreasing functional status of these patients
      and provide important prognostic information.Moreover, in the failing human
      heart, multiple components of the IL-6- glycoprotein (gp)130 receptor system are
      impaired, implicating an important role of this system in cardiac
      pathophysiology.Experimental studies have shown that the common receptor subunit
      of IL-6 cytokines is phosphorylated in response to pressure overload and
      myocardial infarction and that it subsequently activates at least three different
      downstream signaling pathways, the signal transducers and activators of
      transcription 1 and 3 (STAT1/3), the Src-homology tyrosine phosphatase 2 (SHP2)
      Ras-ERK, and the PI3K-Akt system. Gp130 receptor mediated signaling promotes
      cardiomyocyte survival, induces hypertrophy, modulates cardiac extracellular
      matrix and cardiac function. In this regard, the gp130 receptor system and its
      main downstream mediator STAT3 play a key role in cardioprotection. This review
      summarizes the current knowledge of IL-6 cytokines, gp130 receptor and STAT3
      signaling in the heart exposed to physiological (aging, pregnancy) and
      pathophysiological stress (ischemia, pressure overload, inflammation and
      cardiotoxic agents) with a special focus on the potential role of individual IL-6
      cytokines.

PMID- 17530316
TI  - Ischemic preconditioning targets the reperfusion phase.
AB  - Emerging studies suggest that signaling during the myocardial reperfusion phase
      contributes to ischemic preconditioning (IPC). Whether the activation of PKC, the
      opening of the mKATP channel, redox signaling and transient acidosis specifically
      at the time of myocardial reperfusion are required to mediate IPC-induced
      protection is not known. Langendorff-perfused rat hearts were subjected to 35 min
      ischemia followed by 120 min reperfusion at the end of which infarct size was
      determined by tetrazolium staining. Control and IPC-treated hearts were
      randomized to receive for the first 15 min of reperfusion: (1) DMSO (0.02%)
      vehicle control; (2) chelerythrine (10 micromol/l), a PKC antagonist; (3) 5
      hydroxydecanoate (5- HD,100 micromol/l), a mKATP channel blocker; (4) N
      mercaptopropionylglycine (MPG,1 mmol/l), a reactive oxygen species scavenger; (5)
      NaHCO3 (pH 7.6), to counteract any acidosis. Interestingly, all four agents given
      at the time of myocardial reperfusion abolished the infarct reduction elicited by
      IPC (N>6/group): (1) DMSO at reperfusion: 49.3+/-3.6% in control versus 21.0+/
      3.6% with IPC:P<0.05; (2) chelerythrine at reperfusion: 57.1+/-2.5% in control
      versus 60.1+/-3.3% with IPC:P=NS; (3) 5-HD at reperfusion: 53.4+/-6.5 % in
      control versus 42.6+/-4.4% with IPC:P=NS; (4) MPG at reperfusion: 55.3+/-4.6% in
      control versus 43.9+/-5.2% with IPC:P=NS; (5) NaHCO3 at reperfusion 53.4+/-2.5%
      in control versus 59.0+/-3.3% with IPC:P=NS. In conclusion, we report for the
      first time that PKC activation, mKATP channel opening, redox signaling and a low
      pH at the time of myocardial reperfusion are required to mediate the
      cardioprotection elicited by ischemic preconditioning.

PMID- 17530317
TI  - A rare case of aortic coarctation and ventricular septal defect combined with
      alveolar capillary dysplasia.
AB  - We report a rare case of alveolar capillary dysplasia (ACD) associated with
      severe aortic coarctation, hypoplastic aortic arch, and mild hypoplasia of the
      left ventricle. After successful coarctation repair, pulmonary hypertension
      persisted, and despite only minor anomalies on the x-ray, chest computed
      tomography (CT) revealed the presence of primary lung disease. Review of the
      literature suggests that ACD may be associated with left heart obstructions.
      Chest CT is applicable to diagnose ACD precociously.

PMID- 17530318
TI  - Esophageal atresia and diverticulum of Kommerell.
AB  - Diverticulum of Kommerell is an outpouching from the descending aorta that, along
      with an aberrant subclavian artery and ductus arteriosus, may form a vascular
      ring compressing the trachea and/or the esophagus. It has been reported as an
      incidental finding as well as the cause of persistent dysphagia, cough, "asthma,"
      or airway compromise at various ages but has never been reported as a cause of
      esophageal atresia in a newborn. We present a newborn with diverticulum of
      Kommerell, a vascular ring, and esophageal atresia.

PMID- 17530319
TI  - Single coronary artery with fistula, right aortic arch, bicuspid aortic valve,
      and pulmonary stenosis: a rare combination.
AB  - We report a case of a 10-month-old Chinese girl with single left coronary artery,
      left coronary artery-to-right ventricle fistula, pulmonary stenosis, and right
      aorta arch with bicuspid aortic valve. The diagnosis was made by transthoracic
      echocardiography and confirmed by angiography. A surgical repair was performed
      with closure of the fistula at the point where it drained into the right
      ventricle plus a pulmonary valvulotomy.

PMID- 17530320
TI  - Prolonged supine hypertension due to midodrine use in an orthostatic hypotensive
      child.
AB  - Midodrine hydrochloride is a potent peripherally-acting alpha1 agonist that is
      well absorbed and rapidly metabolized to its active metabolite. It has been used
      for the treatment of refractory syncope but has the important side effect of
      supine hypertension. A 10-year-old boy with severe symptomatic orthostatic
      hypotension was treated with midodrine. After therapy, syncope attacks ceased but
      he suffered nighttime headaches, nausea, transient rash and itchy/prickly scalp.
      Midodrine was discontinued when supine hypertension was noticed. However, his
      supine hypertension continued until day 19 after discontinuation. This case shows
      that patients receiving midodrine should be observed for supine hypertension for
      a prolonged period.

PMID- 17530321
TI  - Correlation of plasma B-type natriuretic peptide with shunt severity in patients
      with atrial or ventricular septal defect.
AB  - The goal of this study was to test the utility of bedside plasma concentration of
      B-type natriuretic peptide (BNP) assay as a screen for large shunts in pediatric
      patients with atrial septal defects (ASDs) and ventricular septal defects (VSDs).
      Thirty-five children at a mean age of 70+/-129 weeks with ASD or VSD were
      included in the study. Nine patients had VSD and 26 had ASD. Plasma BNP values
      were compared with the Qp/Qs ratios derived from quantitative Doppler flow
      measurements. Mean BNP was 29+/-42 pg/ml, with a range between<5 pg/ml and 208
      pg/ml. Sixteen patients had Qp/Qs values>1.5 and 19 had values<1.5. The
      difference of mean BNP in these patient groups was statistically significant
      (45+/-56 vs 14+/-17, p=0.03). BNP was positively correlated with shunt
      significance. Receiver operating characteristic curve analysis revealed a
      sensitivity of 69% and a specificity of 79% at a plasma BNP cut-off level
      of>or=20 pg/ml. Bedside measurement of BNP correlates with magnitude of ASD and
      VSD in children. BNP can provide information for the management of children with
      ASD or VSD. It can be used as part of the evaluation of a child with a
      preliminary diagnosis of a congenital defect.

PMID- 17530322
TI  - Management of infants with idiopathic dilatation of the right atrium and atrial
      tachycardia.
AB  - Idiopathic dilatation of the right atrium (IDRA) is a rare anomaly defined as
      isolated enlargement of the right atrium in the absence of other cardiac lesions
      known to cause right atrial dilatation. IDRA is a congenital anomaly with unknown
      pathogenesis and highly variable clinical presentation. Optimal management of
      severe IDRA is controversial and individualized. Literature reports of long-term
      follow-up have been limited. We describe a child with IDRA with rapid atrial
      tachycardia (AT) refractory to both medical and surgical management, and we
      provide long-term follow-up on our two previously reported cases, both of whom
      had documented AT. For infants with AT, the clinical course is unpredictable, and
      medical therapy is the first line of treatment. The decision to proceed with
      surgical resection of a giant right atrium should be made on an individual basis.
      Atrial resection along with a modified right atrial MAZE procedure could be
      considered in infants with life-threatening atrial tachyarrhythmia refractory to
      medical treatment. Surgical scarring of the right atrium may produce substrate
      for atrial arrhythmia, which may also be refractory to medical therapy.
      Histological examination of excised atrial tissue remains inconsistent and not
      contributory to the determination of the etiology of IDRA. Our three infants with
      IDRA illustrate unique features of their variable clinical courses, as well as
      continued difficulties with establishing clear guidelines with regard to surgical
      management of this unusual disorder.

PMID- 17530323
TI  - Traumatic ascending aortopulmonary window following pulmonary artery stent
      dilatation: therapy with aortic endovascular stent graft.
AB  - Endovascular stent grafts have become an established therapy in adults for
      descending thoracic aortic disease. We report a case of a 13-year-old boy with a
      hemodynamically significant traumatic aortopulmonary window following angioplasty
      of pulmonary artery stent. Endovascular stent graft implantation into the
      ascending aorta was performed to seal off the communication, with dramatic
      hemodynamic improvement.

PMID- 17530324
TI  - Cardiac rehabilitation improves heart rate recovery following peak exercise in
      children with repaired congenital heart disease.
AB  - We assessed heart rate (HR) recovery following peak exercise before and after a
      12-week cardiac rehabilitation program in 14 children, 12.1+/-1.8 years of age,
      with repaired complex congenital heart disease (CHD; 11 with Fontan surgery) and
      impaired exercise performance. Exercise testing using bicycle ergometry was
      performed at baseline, after completion of the rehab program and 1.0+/-0.2 years
      after the baseline test. These data were compared to HR recovery in 15 controls
      (age, 12.7+/-2.4 years) with CHD (13 with Fontan surgery) with two serial
      exercise tests at an interval of 1.1+/- 0.3 years. There was no change in peak HR
      between the two serial tests in either group. Peak VO2 improved in the rehab
      group (26.3+/-9.6 ml/kg/min at baseline vs 30.9+/-9.6 ml/kg/min after rehab,
      p=0.01) but remained unchanged in controls on serial testing. One-minute HR
      recovery (in beats per minute) improved significantly following completion of the
      rehab program (27+/-15 at baseline vs 40+/-23 after rehab, p=0.01). Partial
      improvement in 1-minute HR recovery in the rehab group persisted 1 year later (1
      minute HR recovery, 35+/-19; p=0.1 compared to baseline). There was no change in
      1-minute HR recovery over time in the control group (37+/-16 vs 40+/-13, p = not
      significant). In conclusion, HR recovery following peak exercise improves in
      children with CHD after participation in a cardiac rehab program.

PMID- 17530325
TI  - Polymethylmethacrylate for managing frontal bone deformities.
AB  - The correction of bony frontal deformities has been accomplished with a variety
      of autogenous and alloplastic materials. Of the various materials currently
      available, polymethylmethacrylate (PMMA), a valuable biomaterial, has proved to
      be effective in reconstructing deformities of the frontal bone. The authors
      present one case of acquired frontal bone deformity reconstructed by subperiostal
      application of PMMA through a minimally invasive coronal approach. Our
      preliminary experience with this method has been promising.

PMID- 17530327
TI  - Postoperative satisfaction and the patient's body image, life satisfaction, and
      self-esteem: a retrospective study comparing adolescent girls and boys after
      cosmetic surgery.
AB  - BACKGROUND: Cosmetic surgery procedures are more complex for adolescents than for
      adults because there are more factors affecting patient satisfaction, especially
      psychological factors. This study was designed to find answers to four main
      questions: (1) whether postoperative satisfaction rates differ statistically
      between males and females, (2) whether postoperative satisfaction correlates
      significantly with the self-esteem, body image, life satisfaction trilogy, (3)
      what the postoperative patient satisfaction and cosmetic procedure rates are
      among adolescents by years, and (4) whether a statistically significant
      relationship exists between postoperative satisfaction and a willingness of
      adolescents to undergo another cosmetic surgery. METHODS: The study enrolled 86
      of 165 patients who underwent surgery between January 2001 and June 2005. A
      simple poll consisting of 12 simple questions was used to collect data. RESULTS:
      No statistically significant difference was found in postoperative satisfaction
      rates between males and females. The findings show that postoperative
      satisfaction is significantly related to self-esteem, body image, and life
      satisfaction. The patient satisfaction rate was 93.83%, and there was no increase
      in adolescent cosmetic surgery rates over the years. CONCLUSION: Adolescents are
      good candidates for cosmetic surgery, but patients must be evaluated carefully.
      Any suspicion about a patient's psychological status must result in a psychiatric
      consultation.

PMID- 17530328
TI  - A case study of landholder attitudes and behaviour toward the conservation of
      renosterveld, a critically endangered vegetation type in Cape Floral Kingdom,
      South Africa.
AB  - The attitudes and behaviours of private landholders toward the conservation of a
      highly transformed and critically endangered habitat, Overberg Coastal
      Renosterveld (OCR) (a grassy shrubland of the Cape Floral Region, South Africa)
      are described. Personal, semistructured interviews were conducted with
      landholders, representing 40 properties in the Overberg region, on topics such as
      management and utilisation of OCR, the depth of their knowledge of its
      conservation importance, what they perceive its value to be, and the extent of
      their willingness to conserve it. General attitudes toward conservation
      incentives and provincial conservation authorities were also investigated.
      Farmers more willing to conserve were younger, did not necessarily have a better
      education, and owned larger farms (>500 ha) with a greater amount of remnant
      renosterveld (>300 ha) than those less willing to conserve. Attitudes toward the
      OCR were largely negative, related to associated problem plants and animals and
      the fact that it is believed not to be economically advantageous to retain it.
      However, farmers are of the opinion that provision of incentives and increased
      extension support will provide practical positive inducements for conservation.
      Landholder education is paramount to prevent further transformation of critically
      endangered habitats. The success of private-conservation programs depends on the
      attitudes of landowners toward (1) the particular habitat or species to be
      conserved (which can vary depending on the type of land use practised and the
      associated benefits and disadvantages of that habitat type); (2) the conservation
      agency or extension officers responsible for that area; and (3) willingness of
      landowners to participate in a conservation program, which is influenced by
      landowner age, farm size, and the amount of natural habitat left to conserve.

PMID- 17530329
TI  - Economic impacts of zebra mussels on drinking water treatment and electric power
      generation facilities.
AB  - Invasions of nonnative species such as zebra mussels can have both ecological and
      economic consequences. The economic impacts of zebra mussels have not been
      examined in detail since the mid-1990s. The purpose of this study was to quantify
      the annual and cumulative economic impact of zebra mussels on surface water
      dependent drinking water treatment and electric power generation facilities
      (where previous research indicated the greatest impacts). The study time frame
      was from the first full year after discovery in North America (Lake St. Clair,
      1989) to the present (2004); the study area was throughout the mussels' North
      American range. A mail survey resulted in a response rate of 31% for electric
      power companies and 41% for drinking water treatment plants. Telephone interviews
      with a sample of nonrespondents assessed nonresponse bias; only one difference
      was found and adjusted for. Over one-third (37%) of surveyed facilities reported
      finding zebra mussels in the facility and almost half (45%) have initiated
      preventive measures to prevent zebra mussels from entering the facility
      operations. Almost all surveyed facilities (91%) with zebra mussels have used
      control or mitigation alternatives to remove or control zebra mussels. We
      estimated that 36% of surveyed facilities experienced an economic impact.
      Expanding the sample to the population of the study area, we estimated 267
      million dollars (BCa 95% CI = 161 million dollars - 467 million dollars) in total
      economic costs for electric generation and water treatment facilities through
      late 2004, since 1989. Annual costs were greater (44,000 dollars/facility) during
      the early years of zebra mussel infestation than in recent years (30,000
      dollars). As a result of this and other factors, early predictions of the
      ultimate costs of the zebra mussel invasion may have been excessive.

PMID- 17530330
TI  - Urban flood problems in Dhaka, Bangladesh: slum residents' choices for relocation
      to flood-free areas.
AB  - This article applies a stated preference choice model to assess trade-offs that
      residents of two squatter settlements in Dhaka, Bangladesh might consider if they
      were given choices for relocation to flood-free areas. The respondents were asked
      to choose repeatedly from a set of choice cards, which displayed different
      configurations of financial incentives for relocation, such as free or
      inexpensive land, loans or nonrepayable grants, and provisions for temporary or
      permanent employment opportunities. The survey results indicated that despite
      extensive experience with flood problems, many residents of Mirpur and Vasantek
      found that certain configurations of economic incentives were not attractive
      enough for them to relocate to flood-free areas. At the same time, they would
      prefer a reduction in the risk of flooding at their current location. The
      economic incentives that would best assist in increasing voluntary relocation of
      residents from their current locations included free land, nonrepayable grants
      (Taka 20,000), and long-term employment opportunities. Further, differences in
      geographic location (i.e., Mirpur vs. Vasantek), income levels, and membership in
      neighborhood communities were linked with the tendency of residents to stay at
      their current location.

PMID- 17530331
TI  - Regionalization of municipal solid waste management in Japan: balancing the
      proximity principle with economic efficiency.
AB  - The proximity principle - disposing of waste close to its origin - has been a
      central value in municipal solid waste (MSW) management in Japan for the last 30
      years and its widespread adoption has helped resolve numerous "Not in My
      Backyard" issues related to MSW management. However, MSW management costs have
      soared, in large part because of aggressive recycling efforts and because most
      MSW is incinerated in a country that has scarce landfill capacity. In addition,
      smaller, less sophisticated incinerators have been closed because of high dioxin
      emissions. Rising costs combined with the closure of smaller incinerators have
      shifted MSW management policy toward regionalization, which is the sharing of
      waste management facilities across municipalities. Despite the increased use of
      regionalized MSW facilities, the proximity principle remains the central value in
      Japanese MSW management. Municipal solid waste management has become increasingly
      regionalized in the United States, too, but different driving forces are at work
      in these two countries. The transition to regionalized MSW management in Japan
      results from strong governmental control at all levels, with the central
      government providing funds and policy direction and prefectures and
      municipalities being the primary implementing authorities. By contrast, market
      forces are a much stronger force with US MSW management, where local governments 
      with state government oversight - have primary responsibility for MSW
      management. We describe recent changes in Japan's MSW programs. We examine the
      connections between MSW facility regionalization, on the one hand, and, on the
      other hand, the proximity principle, coordination among local governments,
      central government control, and financing mechanisms.

PMID- 17530332
TI  - Assessment of coarse sediment mobility in the Black Canyon of the Gunnison River,
      Colorado.
AB  - The Gunnison River in the Black Canyon of the Gunnison National Park (BCNP) near
      Montrose, Colorado is a mixed gravel and bedrock river with ephemeral side
      tributaries. Flow rates are controlled immediately upstream by a diversion tunnel
      and three reservoirs. The management of the hydraulic control structures has
      decreased low-frequency, high-stage flows, which are the dominant geomorphic
      force in bedrock channel systems. We developed a simple model to estimate the
      extent of sediment mobilization at a given flow in the BCNP and to evaluate
      changes in the extent and frequency of sediment mobilization for flow regimes
      before and after flow regulation in 1966. Our methodology provides a screening
      process for identifying and prioritizing areas in terms of sediment mobility
      criteria when more precise systematic field data are unavailable. The model uses
      the ratio between reach-averaged bed shear stress and critical shear stress to
      estimate when a particular grain size is mobilized for a given reach. We used
      aerial photography from 1992, digital elevation models, and field surveys to
      identify individual reaches and estimate reach-averaged hydraulic geometry.
      Pebble counts of talus and debris fan deposits were used to estimate regional
      colluvial grain-size distributions. Our results show that the frequency of flows
      mobilizing river bank sediment along a majority of the Gunnison River in the BCNP
      has significantly declined since 1966. The model results correspond well to those
      obtained from more detailed, site-specific field studies carried out by other
      investigators. Decreases in the frequency of significant sediment-mobilizing
      flows were more pronounced for regions within the BCNP where the channel gradient
      is lower. Implications of these results for management include increased risk of
      encroachment of vegetation on the active channel and long-term channel narrowing
      by colluvial deposits. It must be recognized that our methodology represents a
      screening of regional differences in sediment mobility. More precise estimates of
      hydraulic and sediment parameters would likely be required for dictating
      quantitative management objectives within the context of sediment mobility and
      sensitivity to changes in the flow regime.

PMID- 17530333
TI  - Land use change and land degradation in southeastern Mediterranean Spain.
AB  - The magnitude of the environmental and social consequences of soil erosion and
      land degradation in semiarid areas of the Mediterranean region has long been
      recognized and studied. This paper investigates the interrelationship between
      land use/cover (LULC) changes and land degradation using remotely sensed and
      ancillary data for southeastern Spain. The area of study, the Xalo River
      catchment situated in the north of the Alicante Province, has been subjected to a
      number of LULC changes during the second half of the 20th century such as
      agricultural abandonment, forest fires, and tourist development. Aerial
      photographs dating back to 1956 were used for the delineation of historic LULC
      types; Landsat ETM+ data were used for the analysis and mapping of current
      conditions. Two important indicators of land degradation, namely, susceptibility
      to surface runoff and soil erosion, were estimated for the two dates using easily
      parametrizable models. The comparison of 1956 to 2000 conditions shows an overall
      "recuperating" trend over the catchment and increased susceptibility to soil
      erosion only in 3% of the catchment area. The results also identify potential
      degradation hot-spots where mitigation measures should be taken to prevent
      further degradation. The readily implemented methodology, based on modest data
      requirements demonstrated by this study, is a useful tool for catchment to
      regional scale land use change and land degradation studies and strategic
      planning for environmental management.

PMID- 17530335
TI  - Middle pancreatectomy: why I rarely do it.

PMID- 17530353
TI  - Bluetongue virus induces apoptosis in cultured mammalian cells by both caspase
      dependent extrinsic and intrinsic apoptotic pathways.
AB  - Bluetongue virus (BTV) causes haemorrhagic disease in sheep and induces death in
      cultured mammalian cells. In the present study, BTV-induced apoptotic pathways in
      Vero cells were elucidated. Cells infected with BTV at 0.1 m.o.i underwent DNA
      fragmentation and membrane blebbing within 48 h postinfection. BTV-induced
      apoptosis was blocked by the pan-caspase inhibitor, z-VAD-FMK. Immuno-blotting
      using anti-caspase-8 and -9 antibodies detected the activation of the respective
      caspases. Flow cytometry analyses following 3, 3' dihexyloxacarbocyanine iodide
      staining revealed the loss of mitochondrial membrane potential. Our study
      confirms the involvement of both caspase-dependent extrinsic and intrinsic
      pathways of apoptosis in BTV-infected cells.

PMID- 17530336
TI  - Surgical therapy for colorectal metastases to the liver.
AB  - Colorectal cancer is the fourth most common type of cancer in the West and the
      second leading cause of cancer-related deaths in the United States. Approximately
      35 to 55% of patients with colorectal cancer develop hepatic metastases during
      the course of their disease. Surgical resection of colorectal liver metastases
      represents the only chance at potential cure, and long-term survival can be
      achieved in 35 to 58% of patients after resection. The goal of hepatic resection
      should be to resect all metastases with negative histologic margins while
      preserving sufficient functional hepatic parenchyma. In patients with extensive
      metastatic disease who would otherwise be unresectable, ablative approaches can
      be used instead of or combined with hepatic resection. The use of portal vein
      embolization and preoperative chemotherapy may also expand the population of
      patients who are candidates for surgical treatment. Despite these advances, many
      patients still experience a recurrence after hepatic resection. More active
      systemic chemotherapy agents are now available and are being increasingly
      employed as adjuvant therapy either before or after surgery. Modern treatment of
      colorectal liver metastasis requires a multidisciplinary approach in an effort to
      increase the number of patients who may benefit from surgical treatment of
      colorectal cancer liver metastasis.

PMID- 17530354
TI  - STR polymorphism of mtDNA D-loop in rhesus macaques of Bangladesh.
AB  - Molecular variation of mitochondrial DNA (mtDNA) was investigated for rhesus
      macaques (Macaca mulatta) of Bangladesh. A partial sequence (583-599 bp) of mtDNA
      containing the second variable region of the D-loop was compared for 39
      individuals from five localities in the country. A total of seven haplotypes were
      detected with substitutional or insertion/deletion mutations. They contained a
      unique polymorphism of pentanucleotide STRs (short tandem repeats). There were at
      least four different length types, from two to five repeats of the unit
      nucleotide. One site of substitution and one site of single nucleotide
      insertion/deletion were also involved in the polymorphism. The mutation hot spots
      of the STR polymorphism were located between the first and second conserved
      sequence blocks (CSB1 and CSB2), as observed previously in some other mammals.
      The geographical distribution of the STR polymorphism revealed local differences;
      the northeastern population was polymorphic with three STR haplotypes, but other
      local populations were simply monomorphic with a single STR haplotype. Molecular
      phylogenetic analysis with reported sequences from outside Bangladesh indicated a
      low substitution diversity of mtDNA in Bangladesh. Clustering results suggested a
      close relationship to India and divergence from Laos and China.

PMID- 17530355
TI  - Drug resistance in antiviral treatment for infections with hepatitis B and C
      viruses.
AB  - Treatments for infections with hepatitis B and C viruses have recently developed
      markedly, and range from nonspecific interferon-based treatments to specific
      antiviral treatments, such as those that inhibit hepatitis virus-coded protein
      production or activity. These developments have contributed to the achievement of
      excellent enhancement of the antiviral effect. On the other hand, the development
      of specific antiviral therapies has created unprecedented problems. Antiviral
      drug-resistant strains of viruses have emerged, leading to a poor prognosis for
      infected patients. Clarification of the mechanisms underlying the emergence of
      such resistance to drugs will be useful for the treatment of such patients. In
      this review, we outline pathological conditions associated with hepatitis B and C
      viruses and their treatments, and discuss the current situation and mechanisms
      underlying the emergence of antiviral drug-resistant strains.

PMID- 17530356
TI  - Intracisternal injection of orexin-A prevents ethanol-induced gastric mucosal
      damage in rats.
AB  - BACKGROUND: Accumulating evidence indicates that orexin-A in the brain stimulates
      vagal flow projecting to the stomach. Since the vagal system plays an important
      role in gastric mucosal integrity, we hypothesized that orexin-A in the brain
      might have a gastroprotective action. METHODS: We examined the effect of
      centrally administered orexin-A on the development of gastric mucosal damage
      evoked by ethanol and its possible mechanism of action in rats. RESULTS:
      Intracisternal but not intraperitoneal injection of orexin-A significantly
      inhibited the severity of gastric mucosal damage by 70% ethanol in a dose
      dependent manner, suggesting that orexin-A acts in the brain to prevent ethanol
      induced gastric mucosal damage. The antiulcer action was observed in rats
      administered with orexin-A centrally but not orexin-B, indicating that the action
      is mediated through orexin 1 receptors. The gastroprotective action of centrally
      administered orexin-A was blocked by pretreatment with atropine, Nomega-nitro-L
      arginine methylester, or indomethacin. CONCLUSIONS: These results suggest that
      orexin-A acts on orexin 1 receptors in the brain to exert a gastroprotective
      action against ethanol. The vagal muscarinic system, nitric oxide, and
      prostaglandins may mediate the cytoprotective action of centrally administered
      orexin-A.

PMID- 17530357
TI  - Clinical analysis of reflux esophagitis following esophagectomy with gastric tube
      reconstruction.
AB  - BACKGROUND: Recently, the rate of postoperative long-term survival has increased
      in cases of esophageal cancer. We report on our analysis of postoperative reflux
      esophagitis (RE) at Tokai University. METHODS: We enrolled 48 patients who
      underwent gastric tube reconstruction after esophagectomy. The diagnosis of RE
      was confirmed by endoscopy. RESULTS: Of the 48 patients, 28 (58.3%) were found to
      have RE. Among the 28 patients with RE, only four (14.3%) reported symptoms. The
      distribution of the severity of RE according to the Los Angeles classification in
      the patients was as follows: grade M, 1 (3.6%); grade A, 2 (7.1%); grade B, 6
      (21.4%); grade C, 17 (60.7%); and grade D, 2 cases (7.1%). Barrett's epithelium
      was detected in 9 of the 28 patients (31%) with RE and in 3 of the 20 (15%)
      patients with no evidence of RE. CONCLUSIONS: To detect the presence of RE as
      well as monitor for recurrence and development of metachronous cancer, we
      consider it important to perform endoscopy regularly over the long term. As
      Barrett's epithelium is frequently encountered, care should be exercised to
      detect the specialized columnar epithelium showing dysplastic changes.

PMID- 17530358
TI  - Association of tannase-producing Staphylococcus lugdunensis with colon cancer and
      characterization of a novel tannase gene.
AB  - BACKGROUND: The relationship between Streptococcus (St.) bovis endocarditis and
      colon cancer is well known. In St. bovis, the biotype I strain (formerly, St.
      gallolyticus) produces tannase that degrades tannins. The aim of this study was
      to investigate the association of tannase-producing bacteria with colon cancer,
      and to identify the major tannase-producing bacteria and the gene involved.
      METHODS: Tannase-producing bacteria were isolated in tannic acid-treated
      selective agar medium from feces and rectal swabs of 357 patients who underwent
      colon endoscopy from 1999 to 2004. RESULTS: Tannase-producing bacteria were
      isolated more frequently from the colon cancer group (24.3%) than from the
      adenoma or normal groups (14.4%; P < 0.05). S. gallolyticus, Staphylococcus (S.)
      lugdunensis, Lactobacillus (L.) plantarum, and L. pentosus were all identified as
      tannase-producing bacteria. Of these, S. lugdunensis was significantly isolated
      from the advanced-stage cancer group (22.2%; P < 0.001) more than from the early
      stage cancer (8.6%) or adenoma (4.9%) groups. The gene (tanA) for tannase in S.
      lugdunensis was cloned and sequenced. The tanA gene was associated with all S.
      lugdunensis but not with other bacteria by Southern blotting and polymerase chain
      reaction. CONCLUSIONS: Tannase-producing S. lugdunensis is associated with
      advanced-stage colon cancer, and the tanA gene is a useful marker for the
      detection of S. lugdunensis.

PMID- 17530359
TI  - Modulatory effects of black tea polyphenols on oxidant-antioxidant profile and
      expression of proliferation, apoptosis, and angiogenesis-associated proteins in
      the rat forestomach carcinogenesis model.
AB  - BACKGROUND: Chemoprevention by dietary constituents has emerged as a novel
      approach to control stomach cancer incidence. We therefore evaluated the
      chemopreventive effects of black tea polyphenols (Polyphenon-B) on oxidant
      antioxidant status, cell proliferation, apoptosis, and angiogenesis during N
      methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced gastric carcinogenesis.
      METHODS: Male Wistar rats were divided into four groups. Rats in group 1 and 2
      were given MNNG (150 mg/kg body weight) by intragastric intubation three times at
      2 week intervals and followed for 26 weeks. Rats in group 2 received in addition
      a basal diet containing 0.05% Polyphenon-B. Group 3 animals were given 0.05%
      Polyphenon-B alone. Group 4 animals served as controls. The status of lipid
      peroxidation and antioxidants and the expression of the lipid peroxidation marker
      4-hydroxy nonenal (4-HNE), proliferating cell nuclear antigen (PCNA),
      glutathiones-transferase (GST)-pi, Bcl-2, Bax, cytochrome C, caspase 3,
      cytokeratins, and vascular endothelial growth factor (VEGF) were used as
      biomarkers. RESULTS: Intragastric administration of MNNG induced well
      differentiated squamous cell carcinomas that showed diminished lipid and protein
      oxidation and an increase in antioxidant status. This was associated with
      increased cell proliferation, angiogenesis, and invasive potential coupled with
      apoptosis evasion as revealed by upregulation of PCNA, GST-pi, Bcl-2,
      cytokeratins, and VEGF and downregulation of Bax, cytochrome C, and caspase 3
      protein expression. Dietary administration of Polyphenon-B effectively suppressed
      MNNG-induced gastric carcinogenesis, as evidenced by modulation of oxidant
      antioxidant status, inhibition of cell proliferation and infiltration, and
      angiogenesis associated with apoptosis induction. CONCLUSIONS: The present study
      provides evidence that Polyphenon-B exerts multifunctional inhibitory effects on
      MNNG-induced gastric carcinogenesis and suggests that it can be developed as a
      potential chemopreventive agent.

PMID- 17530360
TI  - A randomized trial of induction doses of interferon alone or in combination with
      ribavirin or ribavirin plus amantadine for treatment of nonresponder patients
      with chronic hepatitis C.
AB  - BACKGROUND: Efficacy and safety of interferon induction therapy alone or in
      combination with ribavirin or ribavirin plus amantadine were evaluated in chronic
      hepatitis C patients who were nonresponders to primary antiviral treatment.
      METHODS: The study was designed to have 225 HCV nonresponder patients, but at an
      interim analysis the response rate difference between groups was lower than
      expected and the enrollment was stopped when 75 patients had been randomized to
      receive interferon-alpha2a (group A, n = 26), interferon-alpha2a plus 15 mg/kg
      per day of ribavirin (group B, n = 24), or interferon-alpha2a plus ribavirin plus
      200 mg/day of amantadine hydrochloride (group C, n = 25). Treatment duration was
      48 weeks. The dose of interferon was 6 MU/day for 4 weeks followed by 3 MU/day
      for the remaining 44 weeks. RESULTS: On intention-to-treat, the sustained
      virological response at 24 weeks of follow-up was 11.5% in group A, 12.5% in
      group B, and 12% in group C. Therapy was discontinued because of adverse effects
      in three patients in group A (11.5%), three in group B (12.5%), and two in group
      C (8%). CONCLUSIONS: Nonresponders with chronic hepatitis C may achieve a
      sustained virological response rate of approximately 12% if retreated with
      interferon induction treatment followed by administration of a daily dose. The
      addition of ribavirin or amantadine did not seem to improve the response rates.

PMID- 17530361
TI  - Factors associated with the virological response of lamivudine-resistant
      hepatitis B virus during combination therapy with adefovir dipivoxil plus
      lamivudine.
AB  - BACKGROUND: The aim of this study was to investigate the factors associated with
      the response of lamivudine-resistant hepatitis B virus (HBV) during combination
      therapy with adefovir dipivoxil plus lamivudine. METHODS: Sixty-three patients
      with breakthrough hepatitis received a 10-mg once-daily dose of oral adefovir
      dipivoxil. RESULTS: The rates of undetectable serum HBV-DNA were 49.2% after 24
      weeks, 61.9% after 48 weeks, and 67.2% after 72 weeks. The cumulative hepatitis B
      e antigen (HBeAg) loss rates in patients with alanine aminotransferase (ALT)
      levels of more than twice the upper limit of normal (ULN) were significantly
      higher than in patients with ALT less than twice the ULN (P = 0.0145).
      Multivariate analysis revealed that baseline ALT level (P = 0.003) and HBeAg
      status (P = 0.049) were associated with early virological response. CONCLUSIONS:
      Baseline ALT level was associated with HBeAg loss and seroconversion, and
      baseline ALT level and HBeAg status were associated with the virological response
      of lamivudine-resistant HBV during combination therapy with adefovir dipivoxil
      plus lamivudine.

PMID- 17530362
TI  - Type IV collagen 7s domain is an independent clinical marker of the severity of
      fibrosis in patients with nonalcoholic steatohepatitis before the cirrhotic
      stage.
AB  - BACKGROUND: The changes in nonalcoholic fatty liver disease range over a wide
      spectrum, extending from simple steatosis to nonalcoholic steatohepatitis (NASH).
      We investigated the clinical usefulness of the type IV collagen 7s domain and
      hyaluronic acid for predicting the severity of fibrosis before progression to the
      cirrhotic stage in NASH patients. METHODS: The type IV collagen 7s domain and
      hyaluronic acid were measured in 72 patients with histologically verified NASH.
      RESULTS: In a univariate analysis, marked elevation of hyaluronic acid and the
      type IV collagen 7s domain was observed in the NASH patients with advanced
      fibrosis compared with those with mild fibrosis (P = 0.0028, P = 0.0006,
      respectively). For detection of NASH with advanced fibrosis, the area under the
      receiver-operating characteristic curves for type IV collagen 7s domain and
      hyaluronic acid were 0.767 and 0.754, respectively. However, multiple regression
      analysis revealed that the type IV collagen 7s domain, but not hyaluronic acid,
      was significantly elevated in patients with advanced fibrosis even after
      adjustment for age, sex, platelet count, prothrombin time, aspartate
      aminotransferase/alanine aminotransferase ratio, body mass index, and presence of
      underlying type 2 diabetes mellitus, all of which have previously been reported
      as useful predictors of advanced fibrosis in patients with NASH (P = 0.0127, P =
      0.2804, respectively). CONCLUSIONS: This is the first report to demonstrate a
      consistent and profound elevation of the type IV collagen 7s domain in NASH
      patients with advanced fibrosis (before progression to the stage of cirrhosis)
      compared with those with mild fibrosis.

PMID- 17530363
TI  - Diagnosis of hepatic steatosis and fibrosis by transient elastography in
      asymptomatic healthy individuals: a prospective study of living related potential
      liver donors.
AB  - BACKGROUND: This prospective study aimed to assess the ability of transient
      elastography to identify histologic parameters, including steatosis, in
      asymptomatic healthy individuals such as potential liver donors, and to compare
      these findings with results in liver disease patients. METHODS: Forty-seven
      patients with abnormal liver function and/or hepatitis symptoms and 80 living
      related potential liver donors were consecutively enrolled, and liver biopsy and
      a Fibroscan test were performed in each subject. Histologic parameters were
      evaluated according to METAVIR scale by a single pathologist. RESULTS: In liver
      disease patients, stiffness was significantly correlated with fibrosis stage
      (Spearman correlation coefficient, 0.700; P < 0.001), and the optimal stiffness
      cutoff values for F >or= 2, F >or= 3, and F = 4 were 7.35, 8.85, and 15.1 kPa
      respectively. In potential liver donors, however, stiffness was not correlated
      with fibrosis (0.023; P = 0.851). In the latter group, the area under the
      receiver-operating characteristics curve was 0.70 (95% confidence interval, 0.58
      0.81), and the optimal stiffness cutoff value was 4.00 for F >or= 2, which was
      lower than that in liver disease patients. Steatosis was not correlated with
      stiffness (0.088; P = 0.463) in potential liver donors. CONCLUSIONS: Transient
      elastography has limited value for detecting steatosis in asymptomatic healthy
      individuals, and the cutoff value for fibrosis should be reevaluated in these
      subjects.

PMID- 17530364
TI  - Ribonucleotide reductase subunit M2 mRNA expression in pretreatment biopsies
      obtained from unresectable pancreatic carcinomas.
AB  - BACKGROUND: Gemcitabine is an efficacious cytotoxic agent used in the treatment
      of unresectable pancreatic carcinoma (PC). Recently, gemcitabine resistance has
      been associated with the ribonucleotide reductase subunit M2 (RRM2). In this
      prospective study, we hypothesized that RRM2 expression in PC biopsy specimens
      would be a significant predictor of outcome. METHODS: RRM2 mRNA expression in 35
      endoscopic ultrasonography-guided fine needle aspiration biopsy (EUS-FNAB)
      samples was quantified using real-time quantitative reverse transcription
      polymerase chain reaction. RESULTS: Thirty-one of 35 biopsy specimens could be
      assessed for RRM2 expression levels. The mean RRM2 expression relative to
      glyceraldehyde-3-phosphate dehydrogenase was 0.248 (range, 0.00739 to 0.858).
      Eighteen patients (64.5%) had low RRM2 levels, and 13 patients (35.5%) had high
      RRM2 levels with a cutoff of 0.1. The median survival was 8.8 months for patients
      with low RRM2 levels and 5.0 months for patients with high levels (P < 0.05). In
      the low RRM2 expression group, a complete response (CR) was observed in one
      patient, and a partial response (PR) was observed in eight patients. In contrast,
      in the high RRM2 expression group, PR was observed in one patient, and CR was not
      observed. The overall response rate between the high and low expression groups
      was significantly different (50.0% vs. 7.7%, P < 0.05). CONCLUSIONS: RRM2 mRNA
      expression of EUS-FNAB specimens is a key predictive marker of survival in
      gemcitabine-treated patients with PC.

PMID- 17530365
TI  - Efficacy of lamivudine therapy in elderly patients with chronic hepatitis B
      infection.
AB  - BACKGROUND: The aim of this study was to evaluate the efficacy of lamivudine
      therapy in elderly patients with chronic HBV infection. METHODS: Patients aged
      >or=60 years (n = 40) received lamivudine monotherapy between February 1995 and
      September 2005 at Toranomon Hospital. We compared the efficacy of lamivudine
      therapy in these patients and in 639 patients aged <60 years, including 80
      patients aged <60 years matched for sex, hepatitis B e antigen (HBeAg) status,
      and hepatitis B virus (HBV) DNA level. RESULTS: The rates of normalization of
      alanine aminotransferase (ALT) level in 40 patients aged >or=60 years and 639
      patients aged <60 years were 85% versus 76%, and 86% versus 73% at 1 and 3 years,
      respectively. The respective rates of loss of HBV-DNA were 74% versus 74%, and
      76% versus 68% at 1 and 3 years. The respective cumulative emergence rates of the
      YMDD mutant were 16% and 17% at 1 year, and 46% and 49% at 3 years. In 80
      patients <60 years old matched for sex, HBeAg status, and HBV-DNA level, the
      rates of normalization of the ALT level and loss of HBV-DNA were similar to those
      in the 639 patients aged <60 years. The emergence rate of YMDD mutants in
      patients aged >or=60 years were similar to those in matched patients aged <60
      years. Multivariate analyses identified low serum bilirubin (<1 mg/dl) as an
      independent factor associated with the emergence of the YMDD motif mutation in
      patients aged >or=60 years. CONCLUSIONS: Our results suggest that treatment with
      lamivudine is both well tolerated and efficacious in elderly patients with
      chronic HBV infection.

PMID- 17530366
TI  - Familial adenomatous polyposis complicated by chronic myelogenous leukemia:
      response to imatinib mesylate.
AB  - Familial adenomatous polyposis (FAP) is an autosomal dominant disorder
      characterized by colonic polyposis and a predisposition for developing colorectal
      cancer. FAP is frequently complicated by extracolonic disease, but complications
      of leukemia are rare. We present the first case of FAP complicated by chronic
      myelogenous leukemia (CML) in a 38-year-old man. The patient had numerous
      adenomas in the colorectum and a family history compatible with FAP. He was
      diagnosed as having FAP in February 2000. Two years after the diagnosis, he
      developed leukocytosis with the Philadelphia chromosome abnormality, indicating
      complication with CML. Imatinib mesylate was administered for the treatment of
      CML, and hematologic and cytogenetic remission of CML was achieved in 6 months.
      Numerous polyps, 2 to 3 mm in diameter, observed in the rectum prior to the
      administration of imatinib, regressed in size, but not in number, after 1 year of
      treatment with imatinib. Eighteen months later, however, the polyps were
      enlarged. In this patient, imatinib administration led to the remission of CML
      and might also have been responsible for the temporary regression of adenomatous
      polyps of FAP.

PMID- 17530367
TI  - Multiple hepatic pseudotumors on sonography.

PMID- 17530368
TI  - Hepatocellular carcinoma developing six and a half years after a diagnosis of
      idiopathic portal hypertension.

PMID- 17530369
TI  - The development of a new strategy in the management of bone and soft tissue
      tumors.

PMID- 17530370
TI  - ApoB C7623T polymorphism predicts risk for steroid-induced osteonecrosis of the
      femoral head after renal transplantation.
AB  - BACKGROUND: Nontraumatic osteonecrosis of the femoral head (ONFH) is caused by
      disruption of blood flow. This disease often occurs in association with steroid
      treatment. The pathology of steroid-induced ONFH remains unclear, although
      abnormalities in lipid metabolism have been reported to be involved. In this
      study, we examined the differences of gene polymorphism frequencies of
      apolipoprotein B (ApoB) and apolipoprotein A1 (ApoA1), which are important
      proteins for lipid transport, as well as of lipid parameters, between ONFH cases
      and referent patients among those who were subjected to renal transplantation.
      METHODS: Subjects were 158 cases who had undergone renal transplant, including 34
      cases that were diagnosed as ONFH after renal transplantation and 124 cases that
      were not. Four single nucleotide polymorphisms including C7623T and G12619A for
      the ApoB gene and G75A and C83T for the ApoA1 gene were analyzed using polymerase
      chain reaction-restriction fragment length polymorphism (PCR-RFLP) and Taqman
      real-time PCR chemistry. Also, serum levels of low-density lipoprotein (LDL),
      high-density lipoprotein (HDL), ApoB, and ApoA1 were measured. Their relationship
      to ONFH was statistically evaluated. RESULTS: A higher frequency of 7623TT or CT
      of the ApoB gene was observed in ONFH cases than in referent patients (P =
      0.033), resulting in an elevated odds ratio that was statistically significant
      (adjusted odds ratio = 6.37, 95% CI = 1.53-26.5, P = 0.011). No significant
      relationship was observed between other genes and ONFH. Regarding lipid
      parameters, a higher value of ApoB/ApoA1 ratio was observed in cases (P = 0.045).
      CONCLUSION: For the prediction of ONFH, it is useful to analyze ApoB C7623T and
      plasma ApoB/ApoA1 ratio before the administration of steroids.

PMID- 17530371
TI  - Anterolisthesis and retrolisthesis of the cervical spine in cervical spondylotic
      myelopathy in the elderly.
AB  - BACKGROUND: Degenerative spondylolisthesis of the cervical spine has received
      insufficient attention in contrast to that of the lumbar spine. The authors
      analyzed the functional significance of anterior and posterior degenerative
      spondylolisthesis (anterolisthesis and retrolisthesis) of the cervical spine to
      elucidate its role in the development of cervical spondylotic myelopathy (CSM) in
      the elderly. METHODS: A total of 79 patients aged 65 or older who eventually had
      surgical treatment for CSM were evaluated radiographically. RESULTS: Altogether,
      24 patients (30%) had displacement of 3.5 mm or more (severe spondylolisthesis
      group), 31 had displacement of 2.0-3.4 mm (moderate spondylolisthesis group), and
      24 had less than 2.0 mm displacement (mild spondylolisthesis group). The severe
      spondylolisthesis group consisted of 14 patients with anterolisthesis
      (anterolisthesis group) and 10 patients with retrolisthesis (retrolisthesis
      group). Patients with severe spondylolisthesis had a high incidence (93%) of
      degenerative spondylolisthesis at C3/4 or C4/5 and significantly greater cervical
      mobility than those with mild spondylolisthesis. The anterolisthesis group, but
      not the retrolisthesis group, had a significantly wider spinal canal than the
      mild spondylolisthesis group, although the degree of horizontal displacement and
      cervical mobility did not differ significantly between the anterolisthesis and
      retrolisthesis groups. Severe cord compression seen on T1-weighted magnetic
      resonance imaging (MRI) scans and high-intensity spinal cord signals seen on T2
      weighted MRI scans corresponded significantly to the levels of the
      spondylolisthesis. CONCLUSIONS: Degenerative spondylolisthesis is not a rare
      radiographic finding in elderly patients with CSM, which tends to cause intense
      cord compression that is seen on MRI scans. Greater mobility of the upper
      cervical segments may be a compensatory reaction for advanced disc degeneration
      of the lower cervical segments, leading to the development of degenerative
      spondylolisthesis. With a similar degree of displacement, anterolisthesis tends
      to have a greater impact on the development of CSM than retrolisthesis.

PMID- 17530372
TI  - Femoral shaft bowing influences the correction angle for high tibial osteotomy.
AB  - BACKGROUND: The optimal femorotibial angle (FTA) after high tibial osteotomy
      (HTO) is still controversial. Our hypothesis was that FTA itself may not be
      reliable because FTA cannot represent the accurate alignment of the whole lower
      extremity. METHODS: Non-weight-bearing radiographs of the lower extremities were
      taken in 100 Japanese subjects with medial osteoarthritic knees, and seven
      anatomic parameters were assessed. The correction angle by FTA was calculated so
      that the postoperative FTA was set at 166 degrees (14 degrees valgus). Another
      correction angle was calculated so that the mechanical axis passed through the
      lateral one-fourth of the tibial articular surface after HTO. After the
      correlation between two correction angles was assessed, influences of anatomic
      parameters on the discrepancy between two correction angles were assessed.
      RESULTS: There was a high correlation between two correction angles (R2 = 0.777,
      P < 0.001). The mechanical axis passed through the lateral one-fourth of the
      tibial articular surface when the postoperative FTA was set at 166 degrees in 80%
      of subjects. However, discrepancy between the two correction angles was 3 degrees
      or larger in 20% of subjects. Femoral shaft bowing and tibial shaft bowing
      significantly influenced the correction angles. Even though FTA was the same, the
      femoral head shifted medially in cases with lateral bowing of the femoral shaft,
      and the correction angle by FTA should be set larger. On the other hand, the
      correction angle by FTA can be set smaller in knees with medial bowing of the
      femoral shaft. Tibial shaft bowing also influences the correction angle by FTA.
      CONCLUSIONS: The correction angle by FTA for HTO should be calculated taking
      femoral and/or tibial shaft bowing in the frontal plane into account.

PMID- 17530373
TI  - Change of cross-linked telopeptide of type I collagen (ICTP) and other bone
      resorption markers in patients with bone fragility fractures.
AB  - BACKGROUND: The serum concentration of cross-linked telopeptide of type I
      collagen (ICTP) has been reported to be a useful marker and for both diagnosis
      and monitoring of bone metastasis. This study was performed to clarify the
      changes in various bone turnover markers, including ICTP, after bone fragility
      fracture. METHODS: Seventy-six bone fragility fracture patients (14 men and 62
      postmenopausal women; mean age, 77.0 years) were evaluated for bone resorption
      markers, including serum ICTP. We measured urinary N-terminal telopeptides of
      type I collagen (NTX) several times after fracture. Furthermore, serum ICTP,
      serum NTX, urinary deoxypyridinoline (DPD), and urinary C-telopeptide-cross
      linked type I collagen (CTX) were measured at the times of both minimum and
      maximum urinary NTX. RESULTS: Urinary NTX was increased significantly from 86.4
      +/- 57.9 to 214.3 +/- 137.2 nmol BCE/mmol Cr following fracture. Serum ICTP
      showed a similar significant increase from 7.6 +/- 4.7 to 10.4 +/- 5.5 ng/ml in
      bone fragility fracture patients. Furthermore, other markers also showed similar
      increases. The level of increase in urinary NTX (148.0%) was especially high
      compared with other bone resorption markers. On the other hand, the level of
      increase in serum ICTP (36.8%) was similar to that in serum NTX (39.8%). Serum
      ICTP levels were significantly correlated with other bone resorption markers,
      with an especially strong correlation between serum ICTP and serum NTX (r =
      0.647, P < 0.001). The percentage of cases in which ICTP exceeded the cutoff
      value for suspected bone metastasis in postmenopausal women was 73.6%.
      CONCLUSIONS: The value of ICTP increases with bone fragility fracture and is
      correlated with other bone resorption markers, and ICTP obviously exceeded the
      reference value as compared with other bone resorption markers.

PMID- 17530374
TI  - An outcome measure for patients with cervical myelopathy: Japanese Orthopaedic
      Association Cervical Myelopathy Evaluation Questionnaire (JOACMEQ): Part 1.
AB  - BACKGROUND: An outcome measure to evaluate the neurological function of cervical
      myelopathy was proposed by the Japanese Orthopaedic Association in 1975 (JOA
      score), and has been widely used in Japan. However, the JOA score does not
      include patients' satisfaction, disability, handicaps, or general health, which
      can be affected by cervical myelopathy. The purpose of this study was to develop
      a new outcome measure for patients with cervical myelopathy. METHODS: This study
      was conducted in eight university hospitals and their affiliated hospitals from
      February to May 2002. The questionnaire included 77 items. Forty-one questions,
      which were originally listed by the authors, were for evaluation of the physical
      function of the cervical spine and spinal cord. The Medical Outcome Study Short
      Form 36-Item Health Survey (SF-36) was used to examine health-related quality of
      life (QOL). Patients with cervical myelopathy and healthy volunteers were
      recruited at each institution. After analysis of the answers from patients and
      volunteers, irrelevant questions using the following criteria were excluded: (1)
      a question 80% of answers for which were concentrated on one choice, (2) a
      question whose answer was highly correlated with that of other questions, (3) a
      question that could be explained by other questions, and (4) a question for which
      the distribution of the answers obtained from the patients was not different from
      that obtained from the normal volunteers. RESULTS: The patients comprised 164 men
      and 86 women, and the healthy volunteers 96 men and 120 women. Thirteen items
      from the questions about the physical functions of the cervical spine and the
      spinal cord and 11 items from SF-36 remained as candidates that should be
      included in the final outcome measure questionnaire. CONCLUSION: Twenty-four
      questions remained as candidates for the final questionnaire. This new self
      administered questionnaire might be used to evaluate the outcomes in patients
      with cervical myelopathy more efficiently.

PMID- 17530375
TI  - Japanese Orthopaedic Association Cervical Myelopathy Evaluation Questionnaire
      (JOACMEQ): Part 2. Endorsement of the alternative item.
AB  - BACKGROUND: A new self-administered questionnaire as an outcome measure for
      patients with cervical myelopathy was drawn up in Part 1 (Japanese Orthopaedic
      Association Cervical Myelopathy Evaluation Questionnaire, JOACMEQ). Because a
      question with regard to driving a car (C-41) was not suitable for this patient
      group, the authors composed an alternative question related to neck motion (C-41
      2). The purposes of the present study were to perform a secondary survey on
      patients with cervical myelopathy and to statistically analyze the responses to
      validate the JOACMEQ, and also to determine if it was possible to convert item C
      41 to the alternative question. METHODS: A member of the Subcommittee on Low Back
      Pain and Cervical Myelopathy Evaluation from each hospital administered the
      questionnaire to more than 50 patients with cervical myelopathy in each hospital.
      The questionnaire consisted of 25 questions, 24 of which were extracted in the
      primary survey. The authors statistically examined whether it was possible to
      convert question C-41 to C-41-2. RESULTS: Three hundred and sixty-eight patients
      with cervical myelopathy were enrolled in the present study. No questions
      elicited no answer or "I am not sure" in more than 5% of patients except question
      C-41. There were no questions that the patients answered with difficulty. There
      was no tendency that was concentrated on one option as an answer to questions.
      There was a high correlation between questions C-41 and C-41-2. Spearman's
      correlation coefficient and kappa value showed that there was high coincidence
      between the two questions C-41 and C-41-2. It is possible to convert the question
      C-41 to the alternative question C41-2. CONCLUSION: The questionnaire has
      sufficient reliability for clinical use. It is possible that the JOACMEQ will
      prevail and become a global standard to evaluate outcomes in patients with
      cervical myelopathy.

PMID- 17530376
TI  - Comparison of responsiveness of the Japanese Society for Surgery of the Hand
      version of the carpal tunnel syndrome instrument to surgical treatment with DASH,
      SF-36, and physical findings.
AB  - BACKGROUND: The Japanese Society for Surgery of -the Hand version of the Carpal
      Tunnel Syndrome Instrument (CTSI-JSSH), which consists of two parts--one for
      symptom severity (CTSI-SS) and the other for functional status (CTSI-FS)--is a
      self-administered questionnaire specifically designed for carpal tunnel syndrome.
      The responsiveness of the CTSI-JSSH was compared with that of the JSSH version of
      the Disability of Arm, Shoulder, and Hand questionnaire (DASH), the official
      Japanese version of the 36-Item Short Form Health Survey (SF-36, version 1.2),
      and physical examinations to elucidate the role of the CTSI-JSSH for evaluating
      patients with carpal tunnel syndrome. METHODS: Preoperatively, a series of 60
      patients with carpal tunnel syndrome completed the CTSI-JSSH, DASH, and SF-36.
      Results of physical examinations, including grip strength, pulp pinch, and static
      two-point discrimination of the thumb, index, and long fingers, were recorded.
      Three months after carpal tunnel release surgery the patients were asked to fill
      out the same questionnaires, and the physical examinations were repeated. The
      responsiveness of all the instruments was examined by calculating the
      standardized response mean (SRM) and effect size (ES). Correlation coefficients
      were calculated between questionnaire change scores and patient satisfaction
      scores as well as between the CTSI change scores and those of the DASH and SF-36.
      RESULTS: The largest responsiveness was observed in the CTSI-SS (SRM/ES: -1.00/
      1.08) followed by the CTSI-FS (-0.76/-0.63), and bodily pain subscale of SF-36
      (SF-36-BP, 0.45/0.55), and the DASH (-0.46/-0.47). Only the change scores of the
      CTSI-SS had significant correlation with patient satisfaction (r = 0.34, P <
      0.01). An absolute value of Spearman's correlation coefficient of >0.5 was
      observed between the change scores of the CTSI-SS and the DASH, the CTSI-SS and
      the SF-36-BP, the CTSI-FS and the DASH, and the DASH and the SF-36-BP.
      CONCLUSION: The CTSI-JSSH was proven to be more sensitive to clinical changes
      after carpal tunnel release than the other outcome measures and should be used to
      evaluate patients with carpal tunnel syndrome who speak Japanese as their native
      language.

PMID- 17530377
TI  - Comparison of low back pain sites identified by patient's finger versus hand:
      prospective randomized controlled clinical trial.
AB  - BACKGROUND: Accurate diagnosis and appropriate therapy for low back pain are
      based on knowledge of the site of the patient's pain. In clinical settings,
      patients generally indicate the site of low back pain using the hand, but Chapman
      and Syrjala as well as Macnab recommended that the patient should indicate the
      site with the finger. Whether any differences emerge from these methods is an
      important fundamental question. The purpose of this study was to compare low back
      pain sites identified by the patient's finger versus the hand. Specifically, we
      conducted a prospective randomized controlled comparison and investigated the
      surface area and the accuracy of the sites indicated by the two identifications.
      METHODS: Subjects were 137 low back pain patients meeting the following criteria:
      (1) age 18-65 years; (2) low back pain induced by lumbar flexion, extension, or
      lateral bending while standing; (3) absence of leg pain; and (4) pain at only one
      site. Subjects indicated the site of pain by hand and by index finger immediately
      after provocation of pain. A demonstrably reproducible site was outlined on the
      skin. The outlines of the sites were recorded and verified by digital images. The
      body surface area of the sites was determined using NIH Image Version 1.61. Sites
      identified by hand versus index finger were compared on the surface area.
      Additionally, to compare the accuracy of the two identifications, patients were
      asked which of two sites more accurately represented the pain site in outline
      form after the two identification procedures. RESULTS: The surface area of sites
      identified by the finger was significantly smaller than that of sites identified
      by the hand (P < 0.05). Furthermore, a considerably higher proportion,
      approximately 80%, of patients answered that the site of the pain was identified
      more accurately by finger than by hand. CONCLUSIONS: The indication by a finger
      resulted in more accurate, localized identification of the site of low back pain
      than the indication by a hand. The identification of the pain site with a
      patients' finger indication does not directly clarify the etiology of low back
      pain, but it has the potential to provide important information useful for making
      an accurate diagnosis and for determining the appropriate therapy.

PMID- 17530378
TI  - Use of a screw and plate system for a transtrochanteric anterior rotational
      osteotomy for osteonecrosis of the femoral head.
AB  - BACKGROUND: We originally used two or three large cancellous screws for a
      transtrochanteric rotational osteotomy for osteonecrosis. Since January 2002, a
      screw and plate system (K-MAX Adjustable Angle Hip Screw) has been used to obtain
      more rigid fixation at the site of osteotomies. We investigated the clinical and
      radiological results of a transtrochanteric anterior rotational osteotomy.
      METHODS: Between January 2000 and December 2001, a transtrochanteric anterior
      rotational osteotomy with large cancellous screws was performed in 25 hips of 22
      patients, and between January 2002 and March 2005, the K-MAX Adjustable Angle Hip
      Screw was used in 44 hips of 40 patients for treatment of osteonecrosis of the
      femoral head. Japanese Orthopaedic Association (JOA) score, postoperative
      management, and radiographic appearances were investigated. RESULTS: The mean
      preoperative JOA score was 60.8 +/- 12.1 points in the large cancellous screw
      group and 61.5 +/- 14.4 points in the K-MAX Adjustable Angle Hip Screw group.
      This improved to 86.1 +/- 13.3 points in the large cancellous screw group and
      88.7 +/- 6.6 points in the K-MAX Adjustable Angle Hip Screw group at the final
      follow-up. Intentional varus angulations were obtained in 15 of 25 hips in the
      large cancellous screw group and in 36 of 44 hips in the K-MAX Adjustable Angle
      Hip Screw group. Altogether, 23 of 25 (92.0%) cases with large cancellous screws
      started partial weight-bearing 7 weeks after the operation, and 43 of 44 (97.7%)
      cases with the K-MAX Adjustable Angle Hip Screw started 5 weeks after the
      operation. CONCLUSIONS: The K-MAX Adjustable Angle Hip Screw produced clinical
      results similar to those with the large cancellous screws. In addition, partial
      weight-bearing could be started 2 weeks earlier after a transtrochanteric
      anterior rotational osteotomy with the K-MAX Adjustable Angle Hip Screw.

PMID- 17530379
TI  - Evaluation of reparative cartilage after autologous chondrocyte implantation for
      osteochondritis dissecans: histology, biochemistry, and MR imaging.
AB  - BACKGROUND: The aim of this study was to investigate the biochemical properties,
      histological and immunohistochemical appearance, and magnetic resonance (MR)
      imaging findings of reparative cartilage after autologous chondrocyte
      implantation (ACI) for osteochondritis dissecans (OCD). METHODS: Six patients
      (mean age 20.2 +/- 8.8 years; 13-35 years) who underwent ACI for full-thickness
      cartilage defects of the femoral condyle were studied. One year after the
      procedure, a second-look arthroscopic operation was performed with biopsy of
      reparative tissue. The International Cartilage Repair Society (ICRS) visual
      histological assessment scale was used for histological assessment. Biopsied
      tissue was immunohistochemically analyzed with the use of monoclonal antihuman
      collagen type I and monoclonal antihuman collagen type II primary antibodies.
      Glycosaminoglycan (GAG) concentrations in biopsied reparative cartilage samples
      were measured by high performance liquid chromatography (HPLC). MR imaging was
      performed with T1- and T2-weighted imaging and three-dimensional spoiled gradient
      recalled (3D-SPGR) MR imaging. RESULTS: Four tissue samples were graded as having
      a mixed morphology of hyaline and fibrocartilage while the other two were graded
      as fibrocartilage. Average ICRS scores for each criterion were (I) 1.0 +/- 1.5;
      (II) 1.7 +/- 0.5; (III) 0.6 +/- 1.0; (IV) 3.0 +/- 0.0; (V) 1.8 +/- 1.5; and (VI)
      2.5 +/- 1.2. Average total score was 10.7 +/- 2.8. On immunohistochemical
      analysis, the matrix from deep and middle layers of reparative cartilage stained
      positive for type II collagen; however, the surface layer did not stain well. The
      average GAG concentration in reparative cartilage was 76.6 +/- 4.2 microg/mg
      whereas that in normal cartilage was 108 +/- 11.2 microg/mg. Common complications
      observed on 3D-SPGR MR imaging were hypertrophy of grafted periosteum, edema-like
      signal in bone marrow, and incomplete repair of subchondral bone at the surgical
      site. Clinically, patients had significant improvements in Lysholm scores.
      CONCLUSIONS: In spite of a good clinical course, reparative cartilage after ACI
      had less GAG concentration and was inferior to healthy hyaline cartilage in
      histological and immunohistochemical appearance and on MRI findings.

PMID- 17530380
TI  - Effect of periarticular and intraarticular lidocaine injections for sacroiliac
      joint pain: prospective comparative study.
AB  - BACKGROUND: The sacroiliac joint (SIJ) can be a source of low back pain. Previous
      studies indicated that SIJ pain could originate from both the joint capsule and
      the posterior ligamentous tissues. It has not been clarified as to whether an
      intraarticular or periarticular injection procedure is more effective for this
      type of pain. The purpose of this study was to evaluate the effect of two
      injection procedures prospectively. METHODS: After a pain provocation test, an
      intraarticular injection of local anesthetic (2% lidocaine) was performed on the
      first 25 consecutive patients with SIJ pain and a periarticular injection on
      another 25. The periarticular injections were given to one or more sections of
      the posterior periarticular area of the SIJ and to another section in the
      extracranial portion. The effect of these injections was assessed using the
      "restriction of activities of daily life" scoring system from the Japanese
      Orthopaedic Association. RESULTS: The periarticular injection was effective in
      all patients, but the intraarticular one was effective in only 9 of 25 patients.
      An additional periarticular injection was performed in 16 patients who
      experienced no effect from the initial intraarticular injection and was
      considered effective in all of them. The injection into the middle of the
      periarticular area was more effective for SIJ pain. The improvement rate after
      the periarticular injection was 96%, which was significantly higher than that
      after the intraarticular injection, which was 62%. CONCLUSIONS: For patients with
      SIJ pain, periarticular injection is more effective and easier to perform than
      the intraarticular injection and should be tried initially.

PMID- 17530381
TI  - Experimental study of calcium phosphate cement impregnated with dideoxy-kanamycin
      B.
AB  - BACKGROUND: The present study was undertaken to examine whether antibiotic
      impregnated calcium phosphate cement (CPC) would provide a valid means of
      treating osteomyelitis. METHODS: The antibiotic used for the impregnation was
      dideoxy-kanamycin B (DKB), which is available in two forms (powder and liquid).
      Columnar test specimens (diameter 7 mm, height 14 mm) were prepared by adding the
      liquid or powdered DKB. Group A: Three types (6.25-titer, 12.5-titer, 25-titer)
      of test specimen were prepared by mixing the setting solution and DKB solutions
      into cement. Group B: Three types (25-titer, 50-titer, 100-titer) of test
      specimen were prepared by mixing the setting solution and DKB powder into cement.
      Group C: A control specimen was prepared by mixing the setting solution into the
      cement. The study included a consistency test, setting-time test, compressive
      strength test, porosity test, and elution test. RESULTS: The value for the
      consistency test was >23 mm in all test groups. The results of the setting-time
      test showed that the setting time became significantly longer as the DKB content
      increased for groups A group B. Compressive strength decreased as the antibiotic
      content increased, although all specimens remained sufficiently strong for
      clinical application. In group A the porosity did not differ significantly
      depending on the antibiotic content, whereas in group B the porosity increased
      significantly as the antibiotic content increased. In the elution test using
      specimens with the same titer (25 titer), the elution efficiency was higher in
      group A than in group B, and the duration of elution was longer in group A.
      CONCLUSIONS: Although polymethylmethacrylate (PMMA) has been conventionally used
      as a drug-delivery system (DDS), the results of the present study indicate that
      CPC shows better elution efficiency than PMMA. It is thus a promising DDS for the
      treatment of osteomyelitis.

PMID- 17530382
TI  - Osteonecrosis in stroke-prone spontaneously hypertensive rats: effect of
      glucocorticoid.
AB  - BACKGROUND: High-dose administration of a steroid hormone has been associated
      with a major risk of osteonecrosis. In this study we investigated the effects of
      a steroid hormone on the incidence of osteonecrosis of the femoral head in stroke
      prone spontaneously hypertensive rats/Nagasaki (SHRSP/Ngsks). METHODS: A total of
      71 SHRSP/Ngsks were divided into two groups: a control group (C group, n = 40)
      and a steroid hormone group (S group, n = 31) given 5 mg (about 20 mg/kg) of
      methylprednisolone acetate during the 17th week of age. We compared the groups'
      laboratory data, histological appearance, incidence of osteonecrosis, and
      expression of oxidative stress on immunohistochemical analysis using the
      monoclonal antibodies anti-4HNE and anti-8OHdG. RESULTS: The S group showed an
      increase in total cholesterol, with the amounts of high-density lipoprotein, low
      density lipoprotein, and triglycerides all significantly higher than in the C
      group. Histological examination showed that the frequency of necrosis of the
      femoral head was significantly higher in the S group (95.2%) than in the C group
      (51.2%). Most of the histological features of the osteonecrosis demonstrated
      typical features of a similar sort in the two groups. However, the S group showed
      bone marrow spaces in the femoral head that were occupied by an increased number
      of adipocytes and that were swollen, partially degenerative, and necrotic. On
      immunohistochemical analysis, the stains of anti-4HNE and anti-8OHdG antibody
      were stronger in the S group than in the C group. CONCLUSIONS: This study
      confirmed, to a remarkable degree, the suspicion that the administration of
      steroid hormone increases the number of adipocytes in marrow. Fat degeneration
      and necrosis, considered early signs of osteonecrosis, were also observed. It has
      been hypothesized that osteonecrosis is produced by the ischemic change
      accompanying compartment pressure load in marrow, where fat degeneration,
      necrosis, and endothelial cell injury might occur together with oxidative stress.

PMID- 17530383
TI  - Insufficiency fractures in the medial tibial condyle with a special emphasis on
      the radiographic features and differential diagnosis.

PMID- 17530384
TI  - Malignant transformation of a lumbar intradural dermoid cyst.

PMID- 17530385
TI  - Complete dislocation of bilateral knees.

PMID- 17530386
TI  - Bilateral acetabular fractures secondary to a seizure attack caused by antibiotic
      medicine.

PMID- 17530387
TI  - Invasive features of spinal osteosarcoma obtained from whole-mount sections of
      total en bloc spondylectomy.

PMID- 17530388
TI  - Reliability and reproducibility of vertical diffusion cells for determining
      release rates from semisolid dosage forms.
AB  - PURPOSE: USP has formed Advisory Panels to ensure the integrity of laboratory
      procedures for non-oral routes of administration and expects that the panels will
      recommend performance tests (performance qualification, PQ) for these dosage
      forms as well as performance verification tests (PVT) for those PQ tests. An
      integral part of PQ is PVT, in which a standard formulation is first tested in a
      metrologically sound collaborative study to set acceptance criteria. Individual
      laboratories can then test the performance of their product by comparing their
      results to those obtained from the USP collaborative study. These studies are
      guided by metrological principles, e.g., those of the International Organization
      for Standardization (ISO) 43-1, which succinctly states that "one of the main
      uses of proficiency testing schemes is to assess laboratories' ability to perform
      tests competently." MATERIALS AND METHODS: Four laboratories conducted two
      collaborative studies to determine the reliability and reproducibility-
      understood in metrological terms--of release rates from semisolid dosage forms
      using the vertical diffusion cell (VDC). RESULTS: The experiments reported here
      from the second study found that the major contributor to variability is the
      interlaboratory component that may include intermediate precision considerations
      other than analyst. Because all laboratories used the same model equipment, one
      might expect that the observed reproducibility CV was lower than if the
      laboratories used different models or equipment made by different manufacturers.
      Also, more variability was observed with the creams than the other dosage forms.
      CONCLUSIONS: The results from the preliminary collaborative study found
      inconsistency among the laboratories. After operator training, the results from
      the second study were more consistent, suggesting the initial results were
      associated with variations among the laboratories in performing the methods and
      procedures and conducting the protocols. Those results emphasize that although
      the in vitro release procedure is simple and reproducible, training is needed.
      The data presented suggest that testing of in vitro release by VDCs should be
      considered as a PVT for topical semisolid dosage forms. Thus, a standard
      semisolid product is needed, along with a means for setting acceptance criteria.
      The SUPAC-SS Guidance may be helpful in the latter regard.

PMID- 17530389
TI  - Local delivery of indomethacin to arthritis-bearing rats through polymeric
      micelles based on amphiphilic polyphosphazenes.
AB  - PURPOSE: Preparation, in vitro and in vivo evaluation of indomethacin-loaded
      polymeric micelles based on amphiphilic polyphosphazene. METHODS: Amphiphilic
      polyphosphazenes (PNIPAAm/EAB-PPPs) with poly (N-isopropylacrylamide) (PNIPAAm)
      and ethyl 4-aminobenzoate (EAB) as side groups were synthesized through thermal
      ring-opening polymerization and subsequent substitution reactions. Indomethacin
      (IND) loaded polymeric micelles based on PNIPAAm/EAB-PPPs were prepared by
      dialysis procedure. In vitro IND release kinetics was investigated in 0.1 M PBS
      (pH 7.4), while in vivo pharmacokinetics was performed in Sprague-Dawley rats. In
      vivo pharmacodynamic study was carried out based on two animal models, i.e.
      carrageenan-induced acute paw edema and complete Freund's adjuvant (CFA) induced
      ankle arthritis model. RESULTS: Drug loading capacity of micelles based on this
      type of amphiphilic copolymers was mainly determined by copolymer composition and
      the chemical structure of drug. In addition to the compatibility between drug and
      micellar core, hydrogen bonding interaction between drug and hydrophilic corona
      may significantly influence drug loading as well. In vitro drug release in PBS
      suggested that there was no significant difference in release rate between
      micelles based on copolymers with various EAB content. Compared with the rats
      administered with free IND aqueous solution, IND concentration in rats' plasma
      showed a prolonged maintenance in experimental group treated with IND-loaded
      polymeric micelles. In vivo pharmacodynamic study indicated that sustained
      therapeutic efficacy could be achieved through topical injection of the aqueous
      solution of IND-loaded micelles. Local delivery of IND can avoid the severe
      gastrointestinal stimulation, which was frequently associated with oral
      administration as evidenced by ulceration evaluation. CONCLUSIONS: The promising
      results of current preliminary study suggest that this type of amphiphilic
      copolymers could be used as injectable drug carriers for hydrophobic drugs.

PMID- 17530390
TI  - Byrsonic acid--the clue to floral mimicry involving oil-producing flowers and oil
      collecting bees.
AB  - Tetrapedia diversipes and other Apidae (Anthophoridae) may be deceived by floral
      similarities between Malpighiaceae and Orchidaceae of the Oncidiinae subtribe.
      The latter do not usually exudate floral oils. Thus, visitors may pollinate the
      flowers in a deceit/food/pollination syndrome. We studied the chemical
      compositions of Byrsonima intermedia (Malpighiaceae) floral oil and T. diversipes
      (Anthophoridae) cell provisions. From B. intermedia floral oil, we isolated a
      novel fatty acid (3R, 7R)-3,7-diacetoxy-docosanoic acid, here named byrsonic
      acid, and from T diversipes cell provisions we isolated two novel fatty acid
      derivatives 3,7-dihydroxy-eicosanoic acid and 3,7-dihydroxy-docosanoic acid, here
      named tetrapedic acids A and B, respectively. The three fatty acid derivatives
      have common features: possess long chains (20 or 22 carbon atoms) with no double
      bond and either hydroxy or acetoxy groups at carbons 3 and 7. This characteristic
      was also encountered in the fatty acid moiety of oncidinol (2S, 3'R, 7'R)-l
      acetyl-2-[3', 7'-diacetoxyeicosanyl)-glycerol, a major floral oil constituent of
      several Oncidiinae species (Orchidaceae). Thus, both tetrapedic A (C20) and B
      (C22) could be the biotransformation products of oncidinol and byrsonic acid by
      T. diversipes hydrolases. These are the chemical clues for bee visitation and oil
      collecting from both plant species. The results indicate that the
      deceit/pollination syndrome should not be applied to all Oncidiinae flowers.

PMID- 17530391
TI  - Suppressive effect of a standardized mistletoe extract on the expression of
      activatory NK receptors and function of human NK cells.
AB  - Despite long-term use of mistletoe extracts for cancer treatment, their mode of
      action remains elusive. In this study, it was studied in vitro if mistletoe
      extract is able to modulate the expression of natural cytotoxic receptors (NCRs)
      and NKG2D receptor, which stimulate natural killer cell-mediated cytotoxicity.
      Unexpectedly, a mistletoe extract, ABNOBA viscum Fraxini, inhibited the
      expression level of NKp46 and NKG2D receptors in dose- and time-dependent
      manners. The levels of NKp30 and NKG2D receptors were remarkably induced and
      NKp44 was slightly induced after 48 h treatment with IL-2 and IL-15 in both mRNA
      and surface expression. The activatory NK receptors were not induced
      significantly after treatment with IL-12, IL-18, and IL-21 for 48 h. Induction of
      activatory NK receptors by IL-2 and IL-15 was suppressed almost to the untreated
      levels by treatment with mistletoe extract, which appeared to induce apoptosis of
      NK cells in a dose-dependent manner. However, the treatment with IL-2 and IL-15
      did not prevent the mistletoe-induced NK-cell death. Mistletoe extract inhibited
      significantly the cytotoxic activity of resting and IL-2- or IL-15-stimulated NK
      cells. These results suggest that inhibition of survival and function of NK cells
      by mistletoe extract may curtail in part the therapeutic effects of mistletoe.

PMID- 17530392
TI  - Mitochondrial Ca2+ cycle mediated by the palmitate-activated cyclosporin A
      insensitive pore.
AB  - Earlier we found that in isolated rat liver mitochondria the reversible opening
      of the mitochondrial cyclosporin A-insensitive pore induced by low concentrations
      of palmitic acid (Pal) plus Ca(2+) results in the brief loss of Deltapsi
      [Mironova et al., J Bioenerg Biomembr (2004), 36:171-178]. Now we report that Pal
      and Ca(2+), increased to 30 and 70 nmol/mg protein respectively, induce a stable
      and prolonged (10 min) partial depolarization of the mitochondrial membrane, the
      release of Ca(2+) and the swelling of mitochondria. Inhibitors of the Ca(2+)
      uniporter, ruthenium red and La(3+), as well as EGTA added in 10 min after the
      Pal/Ca(2+)-activated pore opening, prevent the release of Ca(2+) and repolarize
      the membrane to initial level. Similar effects can be observed in the absence of
      exogeneous Pal, upon mitochondria accumulating high [Sr(2+)], which leads to the
      activation of phospholipase A(2) and appearance of endogenous fatty acids. The
      paper proposes a new model of the mitochondrial Ca(2+) cycle, in which Ca(2+)
      uptake is mediated by the Ca(2+) uniporter and Ca(2+) efflux occurs via a short
      living Pal/Ca(2+)-activated pore.

PMID- 17530394
TI  - The relations of temperament and emotion self-regulation with suicidal behaviors
      in a clinical sample of depressed children in Hungary.
AB  - Although major depressive disorder (MDD) is associated with suicidal behaviors,
      some depressed individuals are not suicidal and others evidence various forms of
      suicidality. We thus investigated whether aspects of temperament and self
      regulation of dysphoria represent risk factors for DSM-IV suicidality (recurrent
      thoughts of death, recurrent suicidal ideation, suicidal plan, and suicide
      attempt) in depressed youths. Using a sample of children with MDD (N = 407; ages
      7-14 years), recruited from clinical sites across Hungary, we tested the
      hypotheses that: (a) suicidality is related to higher levels of trait negative
      emotionality as well as more maladaptive and fewer adaptive regulatory responses
      to dysphoria and (b) as the severity of suicidal behavior increases, levels of
      trait negative emotionality and dysfunctional emotion regulation also increase.
      We also explored if other aspects of temperament relate to suicidality.
      Children's DSM-IV diagnoses were based on semi-structured interviews and best
      estimate psychiatric consensus. Parents independently provided ratings of their
      children's temperament, and children separately completed an inventory of emotion
      regulation (ER). Using multivariate models, we failed to confirm the hypothesized
      relations of negative trait emotionality and suicidality, but confirmed that high
      maladaptive and low adaptive ER response tendencies increase the odds of suicidal
      behaviors, above and beyond the risk posed by depressive illness severity.
      Unplanned interaction terms between temperament dimensions (other than negative
      emotionality) and ER suggested that at some high-extremes of temperament, ER has
      no impact on suicidality but in their absence, adaptive ER lowers the risk of
      suicidality. The practical implications of the findings are discussed.

PMID- 17530395
TI  - Control of core 2 beta1,6 N-acetylglucosaminyltransferase-I transcription by Sp1
      in lymphocytes and epithelial cells.
AB  - Core 2 beta1,6 N-acetylglucosaminyltransferase-I (C2GnT-I) catalyzes the
      synthesis of one of the major core structures in GalNAc alpha-Ser/Thr O-linked
      oligosaccharides, the core 2 branch. The production of the core 2 branch is
      required for the synthesis of glycoforms that are important for the cellular
      functions of lymphocytes, mucin-producing epithelial cells and other cell types.
      Therefore, proper molecular control of C2GnT-I expression is very important for
      different types of cells. C2GnT-I is transcribed from 4 promoters, with promoter
      2 being the major promoter. C2GnT-I promoter 2 lacks a TATA box and is very GC
      rich. In this study, the analysis of this promoter finds that the transcription
      factor Sp1 is essential for transcription of C2GnT-I in both mesodermally derived
      T-cells (Jurkat) and in endodermal mucin producing epithelial cells (NCI H292).
      In Jurkat cells, all nine of the Sp1 binding sites within the minimal promoter
      region contribute to transcription, and there is a linear relationship between
      the number of Sp1 sites and the transcriptional activity of the promoter. In NCI
      H292 cells, only three of these Sp1 binding sites are required for transcription
      from promoter 2. Chromatin immunoprecipitation confirms that Sp1 binds to
      promoter 2 in NCI H292 cells in vivo.

PMID- 17530397
TI  - A simple and rapid method for preserving RNA of aquatic invertebrates for
      ecotoxicogenomics.
AB  - Here we describe a novel, inexpensive and simple method for preserving RNA that
      reduces handling stress in aquatic invertebrates following ecotoxicogenomic
      experimentation. The application of the method is based on transcriptomic
      experiments conducted on Daphnia magna, but may easily be applied on a range of
      other aquatic organisms of a particular size with e.g. amphipod Gammarus pulex
      representing an upper size limit. We explain in detail how to apply this new
      method, named the "Cylindrical Sieve (CS) system", and highlight its advantages
      and disadvantages.

PMID- 17530396
TI  - Reperfusion injury as a therapeutic challenge in patients with acute myocardial
      infarction.
AB  - Cardiomyocyte death secondary to transient ischemia occurs mainly during the
      first minutes of reperfusion, in the form of contraction band necrosis involving
      sarcolemmal rupture. Cardiomyocyte hypercontracture caused by re-energisation and
      pH recovery in the presence of impaired cytosolic Ca(2+) control as well as
      calpain-mediated cytoskeletal fragility play prominent roles in this type of cell
      death. Hypercontracture can propagate to adjacent cells through gap junctions.
      More recently, opening of the mitochondrial permeability transition pore has been
      shown to participate in reperfusion-induced necrosis, although its precise
      relation with hypercontracture has not been established. Experimental studies
      have convincingly demonstrated that infarct size can be markedly reduced by
      therapeutic interventions applied at the time of reperfusion, including
      contractile blockers, inhibitors of Na(+)/Ca(2+) exchange, gap junction blockers,
      or particulate guanylyl cyclase agonists. However, in most cases drugs for use in
      humans have not been developed and tested for these targets, while the effect of
      existing drugs with potential cardioprotective effect is not well established or
      understood. Research effort should be addressed to elucidate the unsolved issues
      of the molecular mechanisms of reperfusion-induced cell death, to identify and
      validate new targets and to develop appropriate drugs. The potential benefits of
      limiting infarct size in patients with acute myocardial infarction receiving
      reperfusion therapy are enormous.

PMID- 17530398
TI  - Checking the censored two-sample accelerated life model using integrated
      cumulative hazard difference.
AB  - In this paper, new statistical tests for the censored two-sample accelerated life
      model are discussed. From the estimating functions using integrated cumulative
      hazard difference, stochastic processes are constructed. They can be described by
      martingale residuals, and, given the data, conditional distributions can be
      approximated by zero mean Gaussian processes. The new methods, based on these
      processes, provide asymptotically consistent tests against a general departure
      from the model. A graphical method is also discussed. In various numerical
      studies, the new tests performed better than the existing method, especially when
      the hazard curves cross. The proposed procedures are illustrated with two real
      data sets.

PMID- 17530399
TI  - Prevalence of pancreatic insufficiency in inflammatory bowel diseases. Assessment
      by fecal elastase-1.
AB  - Pancreatic insufficiency (PI) may be an extraintestinal manifestation of
      inflammatory bowel diseases (IBD). We report the results of a cross-sectional
      study that was carried out to investigate both the prevalence of PI in IBD
      patients and its clinical course over a 6-month follow-up period. In total, 100
      Crohn's disease (CD) patients, 100 ulcerative colitis (UC) patients, and 100
      controls were screened for PI by the fecal elastase-1 (FE-1) test. The decision
      limits employed were: < or =200 microg/g stool for PI and < or =100 microg/g for
      severe PI. Patients with abnormal FE-1 values were re-tested after 6 months. Odds
      ratios (OR) for PI were estimated by unconditional logistic regression analysis.
      PI was found in 22 UC and 14 CD patients. The OR for the FE-1 test < or =200
      microg/g was 10.5 [95% confidence interval (CI): 2.5-44.8] for IBD patients
      compared to the controls. The risk of PI was related to three or more bowel
      movements per day (OR = 25.0), the passage of loose stools (OR = 7.7), and
      previous surgery (OR = 3.7). At the 6-month follow-up, FE-1 values became normal
      in 24 patients and showed persistently low concentrations in 12. These patients
      had a larger number of bowel movements per day (OR = 5.4), previous surgery (OR =
      5.7), and a longer duration of the disease (OR = 4.2). PI is frequently found in
      IBD patients, particularly in those with loose stools, a larger number of bowel
      movements/day and previous surgery. PI is reversible in most patients, and
      persistent PI is not associated with clinically active disease.

PMID- 17530401
TI  - Pneumatosis intestinalis and portal venous gas without bowel ischemia in a
      patient treated with irinotecan and cisplatin.
AB  - Pneumatosis intestinalis and gas within the portal venous system are findings
      predictive of bowel ischemia. The etiologies of these alarming radiographic signs
      are diverse and not all causes require emergent surgical intervention. The
      combination of pneumatosis intestinalis, portal venous gas, and acidosis
      typically portends bowel ischemia and inevitable necrosis. This case report is
      the first description of benign pneumatosis and portal venous gas secondary to
      irinotecan and cisplatin.

PMID- 17530400
TI  - Protective roles of alpha-calcitonin and beta-calcitonin gene-related peptide in
      spontaneous and experimentally induced colitis.
AB  - Calcitonin gene-related peptide (CGRP) is thought to be involved in the
      regulation of gastric and mesenteric blood flow, in the control of gastric acid
      secretion and in the modulation of intestinal motility, yet the precise
      physiological roles of CGRP remain to be elucidated. To further examine the
      role(s) of CGRP in gastrointestinal function, we examined mutant mice lacking
      alphaCGRP or betaCGRP expression. Mutant mice did not demonstrate any overt
      phenotypic changes, yet exhibited a spontaneous, adult-onset colitis and
      increased colonic damage using a dextran sulfate sodium model of experimental
      colitis. Surprisingly, mice lacking betaCGRP show no obvious alterations in CGRP
      immunoreactivity in the gut, accompanied by an increase in alphaCGRP messenger
      RNA expression, suggesting an adaptive mechanism to compensate for the lack of
      betaCGRP. These data demonstrate that both alphaCGRP and betaCGRP play a
      protective role in the generation of spontaneous colitis, supporting a role for
      both extrinsic and intrinsic CGRP-containing neurons.

PMID- 17530402
TI  - Twenty-four hour tonometry in patients suspected of chronic gastrointestinal
      ischemia.
AB  - BACKGROUND AND AIMS: Gastrointestinal tonometry is currently the only clinical
      diagnostic test that enables identification of symptomatic chronic
      gastrointestinal ischemia. Gastric exercise tonometry has proven its value for
      detection of ischemia in this patients group, but has its disadvantages. Earlier
      studies with postprandial tonometry gave unreliable results. In this study we
      challenged (again) the use of postprandial tonometry in patients suspected of
      gastrointestinal ischemia. METHODS: Patients suspected for chronic
      gastrointestinal ischemia had standard diagnostic work up, including gastric
      exercise tonometry and 24-h tonometry using standard meals. RESULTS: Thirty-three
      patients were enrolled in the study. Chronic gastrointestinal ischemia was
      diagnosed in 17 (52%) patients. The 24-h tonometry correctly predicted the
      presence of ischemia in 13/17 patients, and absence of ischemia in 15/16
      patients. CONCLUSIONS: The use of 24-h tonometry after meals in patients
      suspected of gastrointestinal ischemia seems feasible, with promising accuracy
      for the detection of ischemia.

PMID- 17530403
TI  - Abnormal liver tests as an initial presentation of celiac disease.

PMID- 17530404
TI  - The utility of the random controlled trial for evaluating sexual offender
      treatment: the gold standard or an inappropriate strategy?
AB  - This paper examines the scientific, practical, and ethical issues surrounding the
      employment of the Random Controlled Trial (RCT) in the evaluation of sexual
      offender treatment. Consideration of these issues leads us to conclude that the
      RCT design is not suitable for determining the effectiveness of sexual offender
      treatment. We also examine the RCT study by Marques et al. (Sexual Abuse: A
      Journal of Research and Treatment and Evaluation 17:79-107, 2005) that is often
      held up as the model for the evaluation of sexual offender treatment. We found
      several problems with this study that, in our opinion, reduce its relevance for
      deciding whether treatment is effective with these clients. Finally, we examine
      two alternative strategies for evaluating treatment that may allow treatment
      providers to more readily examine, and report, the results of their programs.

PMID- 17530405
TI  - Sexual offense adjudication and sexual recidivism among juvenile offenders.
AB  - This study compares the recidivism patterns of a cohort of 249 juvenile sexual
      offenders and 1,780 non-sexual offending delinquents who were released from
      secured custody over a two and one half year period. The prevalence of sex
      offenders with new sexual offense charges during the 5 year follow-up period was
      6.8%, compared to 5.7% for the non-sexual offenders, a non-significant
      difference. Juvenile sex offenders were nearly ten times more likely to have been
      charged with a nonsexual offense than a sexual offense. Eighty-five percent of
      the new sexual offenses in the follow-up period were accounted for by the non-sex
      offending delinquents. None of the 54 homicides (including three sexual
      homicides) was committed by a juvenile sex offender. The implications of the
      results for recent public policy trends that impose restrictions that are
      triggered by a sexual offense adjudication are discussed.

PMID- 17530406
TI  - Regional variations in the apparent and tissue-level mechanical parameters of
      vertebral trabecular bone with aging using micro-finite element analysis.
AB  - The aim of this study was to obtain the apparent and tissue-level mechanical
      parameters of vertebral cancellous bones using micro-finite element analysis, and
      to identify the regional variations and their relative differences with respect
      to aging. Ninety trabecular specimens were obtained from six normal L4 vertebral
      bodies of six male cadavers in two age groups, three aged 62 years and three aged
      69 years, and then were scanned using a high-resolution micro-Computed Tomography
      (micro-CT) system. The obtained micro-CT reconstruction models were then
      converted to micro-finite element models. Micro-finite element analyses were done
      to determine the apparent Young's moduli and tissue-level Von Mises stress
      distribution for each trabecular specimen on the longitudinal direction, and
      medial-lateral and anterior-posterior directions (transverse directions),
      respectively. Regional variations about the mechanical parameters at both
      apparent and tissue levels in different transverse layers and vertical columns
      within and between the two age groups were then analyzed. The results showed
      significant decreases in the apparent Young's moduli in each direction with
      aging, and those in the two transverse directions decreased more with aging
      compared with the longitudinal direction. Furthermore, there were no
      statistically significant differences between the mechanical parameters in the
      two transverse directions in both age groups. This study offered an insight into
      the distributions and variations of mechanical properties within a vertebral
      body. The mechanical parameters calculated from this study may help in a better
      understanding of regional fracture risks and the vertebral fracture mechanism in
      the prevention of osteoporotic fracture in elder individuals.

PMID- 17530407
TI  - Model based sensitivity analysis of EMG-force relation with respect to motor unit
      properties: applications to muscle paresis in stroke.
AB  - The sensitivity of the electromyogram (EMG)-force relation to changes in
      motoneuron and muscle properties was explored using a simulation approach, and by
      applying existing motoneuron pool, muscle force, and surface EMG models. The
      simulation results indicate that several factors contribute potently to known
      changes in the EMG-force relation in paretic stroke muscles. First, compression
      of the motor unit recruitment range with respect to the injected current tends to
      generate greater EMG amplitude at a given force, and to produce a highly
      nonlinear EMG-force relation. The overall mean slope of the EMG-force relation
      tends to be flatter, primarily because of this non-linear behavior. Second, with
      reductions of the mean motor unit firing rates, the slope of the EMG-force
      relation also tends to increase especially as the mean firing rates dropped
      substantially below the motor unit fusion frequency. Finally, similar effects
      were observed with a reduction in the number of motor units, and with variation
      in motor unit contractile properties, which also altered the EMG-force relation.
      These findings provide new insight toward our understanding of experimental EMG
      force relations in both normal and pathological states, such as the abnormal EMG
      force relations of paresis muscles in stroke.

PMID- 17530408
TI  - Effects of biomedical sterilization processes on performance characteristics of
      MEMS pressure sensors.
AB  - The effects of steam and gamma sterilization on the performance of bulk
      micromachined pressure sensors were investigated using a variable pressure setup.
      Commercially available piezoresistive MEMS (microelectromechanical systems)
      pressure sensor die were characterized prior and subsequent to sterilization over
      a 0-500 Torr pressure range. The effects of sterilization were examined as
      changes in sensor output voltage (DeltaV) at various applied pressures. For steam
      sterilization, DeltaV decreased with applied pressure ranging from +0.27 mV at
      100 Torr to -0.14 mV at 500 Torr. In contrast, the corresponding values for gamma
      sterilized sensors were lower, decreasing from +0.01 mV 100 Torr to -0.06 mV at
      500 Torr. The increased variation in DeltaV for the steam-sterilized sensors was
      attributed to the formation of an oxide film, which was confirmed using energy
      dispersive X-ray (EDX) spectroscopy. Statistical analysis revealed that the
      effect of both sterilization procedures on sensor performance was insignificant.

PMID- 17530409
TI  - Ultrananocrystalline diamond film as an optimal cell interface for biomedical
      applications.
AB  - Surfaces of materials that promote cell adhesion, proliferation, and growth are
      critical for new generation of implantable biomedical devices. These films should
      be able to coat complex geometrical shapes very conformally, with smooth surfaces
      to produce hermetic bioinert protective coatings, or to provide surfaces for cell
      grafting through appropriate functionalization. Upon performing a survey of
      desirable properties such as chemical inertness, low friction coefficient, high
      wear resistance, and a high Young's modulus, diamond films emerge as very
      attractive candidates for coatings for biomedical devices. A promising novel
      material is ultrananocrystalline diamond (UNCD) in thin film form, since UNCD
      possesses the desirable properties of diamond and can be deposited as a very
      smooth, conformal coating using chemical vapor deposition. In this paper, we
      compared cell adhesion, proliferation, and growth on UNCD films, silicon, and
      platinum films substrates using different cell lines. Our results showed that
      UNCD films exhibited superior characteristics including cell number, total cell
      area, and cell spreading. The results could be attributed to the nanostructured
      nature or a combination of nanostructure/surface chemistry of UNCD, which
      provides a high surface energy, hence promoting adhesion between the receptors on
      the cell surface and the UNCD films.

PMID- 17530410
TI  - A plastic microchip for nucleic acid purification.
AB  - A microchip for purifying nucleic acids from bacterial pathogens was designed and
      fabricated in plastic. The fabricated plastic microchips were tested for their
      ability to purify nucleic acids from the bacteria Listeria monocytogenes (L.
      monocytogenes), Escherichia coli (E. coli), and Salmonella typhimurium (S.
      typhimurium). These chips were constructed using rapid and low-cost plastic
      fabrication techniques including hot embossing and plastic casting. Silicon molds
      fabricated by photolithography and dry etching were used for chip prototyping.
      Zeonor plastic (poly (cycloolefin) resin) and epoxy microchips were fabricated
      using hot embossing and plastic casting, respectively. A low temperature
      sputtering technique was used to coat a layer of silicon dioxide onto the channel
      region for nucleic acid binding in chaotropic salt solutions. The purification
      channels contain an array of features to increase the surface area for DNA
      binding and purification. DNA was quantified with PicoGreen fluorescent dye and
      the quality of the material as a substrate for polymerase chain reaction (PCR)
      was tested using target specific primers. DNA could be recovered from the
      microchip and detected using PCR from a minimum of 10(6) of L. monocytogenes, E.
      coli, and S. typhimurium cells, respectively. With the simplicity of the plastic
      chip's fabrication and DNA purification, our microchip makes it ideal for a
      miniaturized DNA testing system.

PMID- 17530411
TI  - Estimation of zeta potential of electroosmotic flow in a microchannel using a
      reduced-order model.
AB  - A reduced-order model is derived for electroosmotic flow in a microchannel of
      nonuniform cross section using the Karhunen-Loeve Galerkin (KLG) procedure. The
      resulting reduced-order model is shown to predict electroosmotic flows accurately
      with minimal consumption of computer time for a wide range of zeta potential zeta
      and dielectric constant epsilon. Using the reduced-order model, a practical
      method is devised to estimate zeta from the velocity measurements of the
      electroosmotic flow in the microchannel. The proposed method is found to estimate
      zeta with reasonable accuracy even with noisy velocity measurements.

PMID- 17530412
TI  - Surface acoustic wave concentration of particle and bioparticle suspensions.
AB  - A rapid particle concentration method in a sessile droplet has been developed
      using asymmetric surface acoustic wave (SAW) propagation on a substrate upon
      which the droplet is placed. Due to the asymmetry in the SAW propagation,
      azimuthal bulk liquid recirculation (acoustic streaming) is generated. Once the
      local particle concentration is sufficiently high within a particular streamline
      of the acoustic streaming convective flow, shear-induced migration gives rise to
      an inward radial force that concentrates the particles at the centre of the
      droplet. In this paper, a SAW device consists of a 0.75-mm thick, 127.68 degrees
      Y-X-axis-rotated cut, X-propagating LiNbO3 for a substrate and an interdigital
      transducer electrode (IDT) with 25 straight finger pairs in a simple repeating
      pattern, 12 mm aperture, and a wavelength of lambda=440 microm was patterned on
      the substrate. The IDT was then driven with a sinusoidal signal at the resonance
      frequency f0 of 8.611 MHz. To investigate the effect of particle type and size on
      the concentration process, three types of particles were used in this study,
      including fluorescent particles (1 microm), polystyrene microspheres (3, 6, 20,
      45 microm), and living yeast cells (10-20 microm). Different RF powers were
      applied ranging from 120 to 510 mW. The concentration processes occurs within 2
      to 20 s, depending on the particle size, type and input radio frequency (RF)
      power, much faster than currently available particle concentration mechanisms due
      to the large convective velocities achieved using the SAW device. Moreover, this
      concentration method is efficient, concentrating the particles into an aggregate
      one-tenth the size of the original droplet. Most importantly, bioparticles can
      also be concentrated by this method; we have verified that yeast cells are not
      lysed by the SAW radiation during concentration. By using the rapid concentration
      process described in this work, the breadth of applications and measurement
      sensitivity of SAW biosensor systems should be greatly enhanced.

PMID- 17530413
TI  - Microfluidic devices for size-dependent separation of liver cells.
AB  - Liver is composed of various kinds of cells, including hepatic parenchymal cells
      (hepatocytes) and nonparenchymal cells, and separation of these cells is
      essential for cellular therapies and pharmacological and metabolic studies. Here,
      we present microfluidic devices for purely hydrodynamic and size-dependent
      separation of liver cells, which utilize hydrodynamic filtration. By continuously
      introducing cell suspension into a microchannel with multiple side-branch
      channels, cells smaller than a specific size are removed from the mainstream,
      while large cells are focused onto a sidewall in the microchannel and then
      separated into two or three groups. Two types of PDMS-glass hybrid microdevices
      were fabricated, and rat liver cells were successfully separated. Also, cell
      size, morphology, viability and several cell functions were analyzed, and the
      separation performances of the microfluidic devices were compared to that of a
      conventional centrifugal technique. The results showed that the presented
      microfluidic devices are low-cost and suitable for clinical use, and capable of
      highly functional separation with relatively high-speed processing.

PMID- 17530414
TI  - Generation of stable concentration gradients in 2D and 3D environments using a
      microfluidic ladder chamber.
AB  - We have developed a simple microfluidic device for generating stable
      concentration gradients in 2D and 3D environments. The device, termed the Ladder
      Chamber, uses a two-compartment diffusion system to generate steady state
      gradients across flow-free channels that connect the source and sink channels. To
      demonstrate the utility of the Ladder Chamber for cell migration, neutrophil
      chemotaxis was successfully observed in soluble chemoattractant (IL-8) gradient.
      The Ladder Chamber's simple design and experimental implementation make it an
      attractive approach for investigating cell migration and other biological
      experiments in well-defined gradients in 2D surfaces as well as in 3D gels.

PMID- 17530415
TI  - Two cases of Kallmann syndrome associated with empty sella.
AB  - Kallmann syndrome (KS) is a developmental disease characterized by the
      association of isolated hypogonadotropic hypogonadism and anosmia/hyposmia. We
      report an unusual presentation of two females with KS and empty sella. These
      females, aged at 20 and 29-year-old, presented primary amenorrhea with
      prepubertal estradiol and low gonadotropin levels. No other significant clinical
      signs were observed. Empty sella was observed on MRI in both cases. Sequencing of
      FGFR1 gene, recently implicated in autosomal form of KS, was performed and one
      splicing mutation (IVS14 + 1G > A) was identified in one patient.

PMID- 17530416
TI  - Remission of acromegaly following long-term therapy with cabergoline: report of
      two cases.
AB  - Dopamine agonists are effective in some patients with acromegaly and in this
      condition treatment is considered to be chronic. We describe two acromegalic
      patients who responded adequately to the long-acting dopamine agonist
      cabergoline, but surprisingly maintained normal GH and IGF-I levels once therapy
      was discontinued after 42 and 76 months because of possibly related side effects.
      A 32-year-old woman with mild acromegaly (IGF-I: 423 microg/l, GH after OGTT: 2.5
      microg/l, adenoma 4 mm) was treated with cabergoline as primary therapy and
      reached safe GH levels (2 microg/l or less) and normal IGF-I levels with 3.5 mg
      cabergoline weekly. After 42 months of therapy the patient experienced a
      progressive decrease of libido, which she attributed to the intake of
      cabergoline. After stopping medication, serum levels of GH and IGF-I remained
      normal during the following 2.5 years. A 53-year-old man with moderate acromegaly
      (serum IGF-I: 547 microg/l, GH after OGTT: 5.9 microg/l, adenoma 7 mm) preferred
      cabergoline as primary therapy. Serum GH levels below 2 microg/l and normal
      levels of IGF-I were obtained with 3.5 mg cabergoline weekly. When the patient
      experienced severe stomach pains after 76 months of treatment, cabergoline was
      held responsible and discontinued. Serum GH and IGF-I did not increase again and
      stayed at the same level during a follow-up of 5.5 years. These two cases
      demonstrate that acromegalic patients with a good response to cabergoline may
      occasionally remain in remission after stopping therapy. This phenomenon has
      previously only been described in patients with a prolactinoma.

PMID- 17530417
TI  - Ghrelin in neuroendocrine organs and tumours.
AB  - Ghrelin is a 28 amino-acid hormone with multiple functions. It is predominantly
      produced by the stomach but has also been detected in other organs, including the
      small intestine, pancreas, hypothalamus and pituitary, as well as in the immune
      system and almost every other normal human tissue examined. It is also present in
      neuroendocrine tumours, pituitary adenomas, endocrine tumours of the pancreas,
      breast tumours, and thyroid and medullary thyroid carcinomas. Ghrelin is a brain
      gut peptide with growth hormone-releasing and appetite-inducing activities, and
      is the endogenous ligand of the G protein-coupled growth hormone secretagogue
      receptor (GHS-R). In this review we comprehensively summarize the available data
      regarding (a) the expression of ghrelin and the GHS-R in normal endocrine tissues
      and in pituitary adenomas and neuroendocrine tumours, (b) the levels of
      circulating ghrelin in patients with pituitary adenomas and neuroendocrine
      tumours and (c) the effects of ghrelin administration in these patients on the
      levels of other hormones and on the rate of proliferation of the tumour. It is
      clear that ghrelin has many more functions and is involved in many more processes
      than was initially postulated, and its endocrine, paracrine and autocrine effects
      play a role in its physiological and pathophysiological functions.

PMID- 17530419
TI  - Molecular identification and characterization of the tomato flagellin receptor
      LeFLS2, an orthologue of Arabidopsis FLS2 exhibiting characteristically different
      perception specificities.
AB  - Bacterial flagellin is known to stimulate host immune responses in mammals and
      plants. In Arabidopsis thaliana, the receptor kinase FLS2 mediates flagellin
      perception through physical interaction with a highly conserved epitope in the N
      terminus of flagellin, represented by the peptide flg22 derived from Pseudomonas
      syringae. The peptide flg22 is highly active as an elicitor in many plant
      species. In contrast, a shortened version of the same epitope derived from
      Escherichia coli, flg15(E coli), is highly active as an elicitor in tomato but
      not in A. thaliana or Nicotiana benthamiana. Here, we make use of these species
      specific differences in flagellin perception abilities to identify LeFLS2 as the
      flagellin receptor in tomato. LeFLS2 is most closely related to AtFLS2,
      indicating that it may represent the flagellin receptor of tomato. Expression of
      the LeFLS2 gene in Arabidopsis did not result in accumulation of its
      corresponding gene product, as indicated by experiments with LeFLS2-GFP fusions.
      In contrast, expression of LeFLS2-GFP fusions in N. benthamiana, a species that,
      like tomato, belongs to the Solanaceae, was obviously functional. N. benthamiana
      plants transiently expressing a LeFLS2-GFP fusion acquired responsiveness to
      flg15(E coli) to which they are normally unresponsive. Thus, LeFLS2 encodes a
      functional, specific flagellin receptor, the first to be identified in a plant
      family other than the Brassicaceae.

PMID- 17530420
TI  - Desorption characteristics of kaolin clay contaminated with zinc from
      electrokinetic soil processing.
AB  - A number of bench scale laboratory column tests were carried out using a newly
      designed and developed electrokinetic cell to investigate the fundamental
      behavior of zinc-spiked kaolin clay subjected to an electric field. Laboratory
      investigations focused on (i) zinc migration by the combined effects of
      electromigration and electro-osmosis and (ii) the electrically induced desorption
      characteristics of zinc-contaminated kaolin that occurred during processing. The
      correlations of the applied voltage gradient, electro-osmotic flow rate, and the
      development of a pH gradient were examined and evaluated. The results showed that
      the removal efficiency was high during the early stage of processing due to rapid
      desorption by electrokinetic effects in the cathode region. However, the majority
      of zinc migrating from the anode was precipitated due to the high pH environment
      in the cathode region.

PMID- 17530421
TI  - Life course determinants for early disability pension: a follow-up of Norwegian
      men and women born 1967-1976.
AB  - BACKGROUND: Most studies on disability pension (DP) have focused on work
      conditions, socio-economic status and other contemporary factors. We wanted to
      study possible determinants of an early DP with a life course perspective within
      a large register-based cohort, with a main focus on the biological and social
      factors from childhood. METHODS: We established a longitudinal, population-based
      cohort of all persons liveborn in Norway between 1967 and 1976. Through linkage
      between several national registers we obtained personal data on biological/health
      related as well as social background factors. After excluding persons who died,
      emigrated or were granted a DP before age 20 years (at which age follow-up
      started) and persons who did not become gainfully employed during the study
      period, the study population consisted of 595,393 persons. They were categorized
      into four strata according to gender and educational attainment. Adjusted hazard
      ratios (HR) for granting a DP until the end of 2003 and the corresponding
      population attributable risks (PAR) were computed. RESULTS: A total of 9,649
      persons (1.6%) were granted a DP during follow-up. The disability risk was
      slightly higher among women than among men (1.7% vs. 1,5%). The following PARs
      were found: birth weight below the mean 5.7%, chronic childhood disease 6.8%,
      maternal marital status 4.4% and parental disability 8.8%. Low educational
      achievement was highly associated with DP, with a PAR more than twice as high as
      the overall PAR for the childhood factors. CONCLUSIONS: Early DP is associated
      with several biological and social background factors from childhood. It also
      shows a strong dependency on educational achievement.

PMID- 17530422
TI  - Of new times, new opportunities, and old problems.

PMID- 17530423
TI  - Specific isolation of disseminated cancer cells: a new method permitting
      sensitive detection of target molecules of diagnostic and therapeutic value.
AB  - Molecular studies of rare cells, such as circulating cancer cells, require
      efficient pre-enrichment steps to obtain a pure population of target cells for
      further characterization. We have developed a two-step approach, starting with
      immunomagnetic enrichment, followed by specific isolation of individual, easily
      identifiable bead-rosetted target cells using a new semi-automated CellPick
      system. With this procedure, 1-50 live target cells can now be isolated. As a
      model system, we spiked a small number of tumor cells into millions of normal
      mononuclear cells (MNCs). Efficient isolation of pure target cells was obtained
      by use of the CellPick system, and the nature of isolated, bead-rosetted cells
      was verified by use of FISH. Single breast cancer cells were picked directly into
      an RNA preserving lysis buffer, reverse transcribed, and PCR amplified with two
      cDNA specific primer sets. With the isolated cells we consistently obtained both
      ubiquitously expressed and tumor cell specific PCR products. We also performed a
      successful mutation analysis of single cells using PCR and cycling temperature
      capillary electrophoresis (CTCE). This may have significant clinical implications
      in cancer and in other diseases, e.g. in characterizing micrometastatic cancer
      cells in blood and lymph nodes to help identifying patients who most likely will
      respond to therapies like tyrosine kinase inhibitors and compounds targeting
      specific mutations. By use of the CellPick system it is possible to specifically
      isolate bead-rosetted or otherwise labelled target cells from a heterogeneous
      cell population for further molecular characterization.

PMID- 17530424
TI  - Sarcomere dynamics during muscular contraction and their implications to muscle
      function.
AB  - This article attempts to identify the key aspects of sarcomere inhomogeneity and
      the dynamics of sarcomere length changes in muscle contraction experiments and
      focuses on understanding the mechanics of myofibrils or muscle fibres when viewed
      as independent units of biological motors (the half-sarcomeres) connected in
      series. Muscle force generation has been interpreted traditionally on the basis
      of the kinetics of crossbridge cycling, i.e. binding of myosin heads to actin and
      consecutive force generating conformational change of the head, under controlled
      conditions and assuming uniformity of sarcomere or half-sarcomere behaviour.
      However, several studies have shown that re-distribution of internal strain
      within myofibrils and muscle fibres may be a key player, particularly, during
      stretch or relaxation so that force kinetics parameters are strongly affected by
      sarcomere dynamics. Here, we aim to shed light on how force generation,
      crossbridge kinetics, and the complex sarcomere movements are to be linked and
      which mechanical concepts are necessary to develop a comprehensive contraction
      model of a myofibril.

PMID- 17530425
TI  - Alar photoplethysmography: a new methodology for monitoring fluid removal and
      carotid circulation during hemodialysis.
AB  - OBJECTIVE: Hemodialysis (HD) hemoconcen tration measurements may not predict
      hypotension, and are confounded by impaired compensatory responses to
      ultrafiltration (UF). We devised noninvasive photople thysmograph (PPG)
      technology to monitor carotid blood flow at the nasal alar, quantify cardiac and
      respiratory components, and study the effect of UF and resistance breathing in HD
      patients and blood donors. METHODS: The PPG was recorded using a novel alar probe
      in 40 subjects (20 each group), before and after their procedure, with 3 airway
      resistances. Raw data were separated into a low frequency component (LFC, based
      on the effect of respiration on thoracic pressure and blood capacitance) and a
      rapid pulsatile cardiac component (PCC), yielding 3 measures of carotid flow and
      vascular tone. RESULTS: The device produced stable signals amenable to automated
      processing. The LFC (respiration-induced variation in carotid flow) increased
      with UF (P as low as 0.03, depending on airway resistance), not changing in blood
      donors. Two PCC variables (measuring blood vessel distention with each heart
      beat) decreased (P < or = 0.03) with blood donation, but not UF. CONCLUSIONS:
      This new noninvasive PPG method detects altered respiration-associated carotid
      circulation during UF. With blood donation there is dampening of pulsatile vessel
      distention, consistent with increased vascular tone. That compensatory mechanism
      was impaired in HD patients and helps explain their instability with fluid
      removal.

PMID- 17530426
TI  - Breast cancer in pregnancy: a literature review.
AB  - PURPOSE: Breast cancer in pregnancy is a clinically challenging situation for
      patients and their physicians. A review of the literature was performed to help
      identify optimal treatment strategies. METHODS: A Medline search between 1966 to
      the present using the keywords "breast", "carcinoma", and "pregnancy" revealed
      numerous hits, from which English-language articles including epidemiologic
      studies, case series, and general summaries were reviewed. RESULTS: There is a
      paucity of prospective studies regarding diagnosis and treatment of breast cancer
      in pregnancy due to its rarity. However a general review of the literature
      database reveals that women diagnosed with breast cancer during pregnancy have
      similar disease characteristics to age-matched controls. Surgery remains the
      mainstay of treatment of breast cancer during pregnancy, and in some
      circumstances breast-conserving surgery is an acceptable option. Adjuvant
      treatment can proceed with some modifications that minimize harm to the fetus,
      namely limiting radiation exposure and timing chemotherapy properly. Post-partum
      decisions regarding lactation and future fertility should be addressed on a per
      patient basis. CONCLUSION: Breast cancer in pregnancy is an uncommon phenomenon
      but one which poses dilemmas for patients and their physicians. A multi
      disciplinary approach is recommended for optimal clinical-decision making.

PMID- 17530427
TI  - Gemcitabine in the management of metastatic breast cancer: a systematic review.
AB  - BACKGROUND: A systematic review of the evidence for gemcitabine chemotherapy,
      alone or in combination, in women with metastatic/advanced breast cancer was
      undertaken in order to determine gemcitabine's role in the first-line and/or
      second-line or greater setting. METHODS: MEDLINE, EMBASE, the American Society of
      Clinical Oncologists, San Antonio Breast Cancer Symposium proceedings, and the
      Cochrane Library were searched through September 2006 for randomized controlled
      trials and non-randomized phase two trials. RESULTS: Eighty-three trials were
      identified, including four randomized phase III trials. All of the phase III
      trials included first-line patients. Two of the phase III trails demonstrated
      clinical benefit with gemcitabine-based chemotherapy in terms of superior
      efficacy or less toxicity while two phase III trials found no clinical benefit
      based on less efficacy or increased toxicity. Although 78 phase II trials of
      gemcitabine alone or in combination with other chemotherapy agents were
      identified, few combinations showed results compelling enough to warrant
      randomized trials. CONCLUSION: Available data do not support the acceptance of
      gemcitabine as a standard therapeutic option in women with metastatic breast
      cancer in the third-line or greater setting, nor should it be considered as first
      line therapy in anthracycline naive women. Gemcitabine appears to be most
      effective when administered with a taxane (docetaxel/paclitaxel) in the first- or
      second-line setting, with gemcitabine/taxane combinations representing a viable
      alternative to currently accepted taxane combinations such as
      capecitabine/docetaxel. There is no evidence at this time to support the use of
      gemcitabine triplets, given the equal efficacy to anthracycline triplets and the
      added toxicity.

PMID- 17530428
TI  - Effects of a combined aerobic and resistance exercise program in breast cancer
      survivors: a randomized controlled trial.
AB  - Few randomized controlled trials have examined the effects of combined aerobic
      and resistance training in breast cancer survivors soon after completing adjuvant
      therapy. Breast cancer survivors (N=58) within 2 years of completing adjuvant
      therapy were randomly assigned to an immediate exercise group (IEG; n=29) or a
      delayed exercise group (DEG; n=29). The IEG completed 12 weeks of supervised
      aerobic and resistance exercise, three times per week. The DEG completed the
      program during the next 12 weeks. Participants completed patient-rated outcomes
      at baseline, 6, 12, 18 and 24 weeks. The primary endpoint was overall quality of
      life (QoL) measured by the Functional Assessment of Cancer Therapy-Breast scale.
      Secondary endpoints were fatigue, social physique anxiety, and physical fitness.
      Follow-up data was obtained on 97% of participants and exercise adherence was
      61.3%. Repeated measures analyses of variance revealed a significant group by
      time interaction for overall QoL (P<0.001). Specifically, QoL increased in the
      IEG from baseline to 12 weeks by 20.8 points compared to a decrease in the DEG of
      5.3 points (mean group difference=26.1; 95% CI=18.3-32.7; P<0.001). From 12 to 24
      weeks, QoL increased in the DEG by 29.5 points compared to an increase of 6.5
      points in the IEG (mean group difference=23.0; 95% CI=16.3-29.1; P<0.001).
      Similar results were obtained for the secondary endpoints. Combined aerobic and
      resistance exercise soon after the completion of breast cancer therapy produces
      large and rapid improvements in health-related outcomes.

PMID- 17530429
TI  - Phase III randomized multicenter study on the effects of adjuvant CMF in patients
      with node-negative, rapidly proliferating breast cancer: twelve-year results and
      retrospective subgroup analysis.
AB  - The randomized multicenter study on rapidly proliferating breast cancer, assessed
      according to thymidine labelling index (TLI), was activated at the end of the
      1980s. The present work investigated whether and to what degree the short-term
      advantages observed from adjuvant CMF (cyclophosphamide, methotrexate, 5
      fluorouracil) were maintained at a longer follow-up. Two hundred and eighty-one
      patients with node-negative and high TLI tumors were randomized to receive six
      cycles of CMF or no further treatment. At a median follow-up of 12 years, CMF
      produced a 25% and 20% relative reduction in relapse and death cumulative
      incidence, respectively. A breakdown analysis identified a subgroup of patients
      with intermediate proliferating tumors for whom a 70% and 73% reduction in
      relapse and death was observed in the intention-to-treat population. An even
      higher reduction of 80% and 84% in relapse and death was seen for the patients
      who had received the full CMF dose. We identified a subgroup of patients with
      intermediate proliferating tumors in whom the high benefit obtained from adjuvant
      CMF was maintained at a long-term follow up.

PMID- 17530430
TI  - Uncertainty assessment of mapping mercury contaminated soils of a rapidly
      industrializing city in the Yangtze River Delta of China using sequential
      indicator co-simulation.
AB  - Accurate characterization of heavy-metal contaminated areas and quantification of
      the uncertainties inherent in spatial prediction are crucial for risk assessment,
      soil remediation, and effective management recommendations. Topsoil samples (0-15
      cm) (n=547) were collected from the Zhangjiagang suburbs of China. The sequential
      indicator co-simulation (SIcS) method was applied for incorporating the soft data
      derived from soil organic matter (SOM) to simulate Hg concentrations, map Hg
      contaminated areas, and evaluate the associated uncertainties. High variability
      of Hg concentrations was observed in the study area. Total Hg concentrations
      varied from 0.004 to 1.510 mg kg(-1) and the coefficient of variation (CV)
      accounts for 70%. Distribution patterns of Hg were identified as higher Hg
      concentrations occurred mainly at the southern part of the study area and
      relatively lower concentrations were found in north. The Hg contaminated areas,
      identified using the Chinese Environmental Quality Standard for Soils critical
      values through SIcS, were limited and distributed in the south where the SOM
      concentration is high, soil pH is low, and paddy soils are the dominant soil
      types. The spatial correlations between Hg and SOM can be preserved by co
      simulation and the realizations generated by SIcS represent the possible spatial
      patterns of Hg concentrations without a smoothing effect. Once the Hg
      concentration critical limit is given, SIcS can be used to map Hg contaminated
      areas and quantitatively assess the uncertainties inherent in the spatial
      prediction by setting a given critical probability and calculating the joint
      probability of the obtained areas.

PMID- 17530431
TI  - Ecological quality boundary-setting procedures: the Gulf of Riga case study.
AB  - Two approaches for setting ecological class boundaries, response curves and a
      simplified mathematical boundary-setting protocol, were tested for coastal,
      transitional and open waters in the Gulf of Riga, Baltic Sea. The simplified
      mathematical boundary-setting protocol defines acceptable ecological status based
      on expert judgment by a uniform relative deviation from reference conditions. In
      contrast, response curves derive class boundary definitions from observed changes
      in biological quality elements along environmental pressure gradients for class
      boundary definitions. Identification of relevant environmental pressures for the
      construction of response curves was based on a conceptual model of eutrophication
      in the Gulf of Riga. Response curves were successfully established for summer
      chlorophyll a and transparency, as well as for macrozoobenthos abundance in the
      Central Gulf, macrozoobenthos biotic coefficient in the Southern Gulf, and
      maximum depth of phytobenthos in the Northern Gulf. In the Gulf of Riga response
      curves almost always permitted a larger deviation from reference conditions than
      the 50% deviation applied for the simplified mathematical boundary-setting
      protocol. The case study clearly demonstrated that class boundary definitions
      should take into account the sensitivity of the target water body. Also, the
      class boundaries for different ecological quality elements were internally more
      consistent than those derived by the simplified mathematical boundary-setting
      protocol.

PMID- 17530432
TI  - Trends of organochlorine pesticides in drinking water supplies.
AB  - The effectiveness of the treatment process for the removal of pesticides in the
      final water supplies in Delhi has been evaluated. Samples were collected during
      2000-2005 from five water treatment plants (WTPs). Analysis was carried out to
      identify pesticides, which are more commonly encountered in treated drinking
      water. In most of the treatment plants, the concentrations of lindane, total
      endosulphan and total DDT were significantly less in the finished water.
      Monitoring of these less soluble pesticide in the finished water from WTPs was
      done quarterly to arrive at the quality trends and to plan for the mitigation
      action, in case the concentration of the parameter exceeded at any site or time.

PMID- 17530433
TI  - Hero or has-been: is there a future for altruism in medical education?
AB  - The term 'altruism' is often used without definition, leading to contradictions
      in what we expect from medical students. In this reflection paper, we critique
      the concept of 'altruism' from the perspective of moral philosophy and social
      psychology and challenge its unquestioned usage within the medical education
      literature, especially that emerging from the USA. We will argue that 'altruism'
      is a social construction with a particular history, stemming from Kantian
      philosophy and perpetuated within newer disciplines such as social psychology. As
      it currently stands, 'altruism' seems to mean utter self-sacrifice--a position
      contradictory to recent recommendations by regulatory bodies in the UK, which
      suggest that graduates should look after the 'self' and achieve a work-life
      balance. In this article, we argue that it is undesirable to have 'altruism' as a
      learning outcome for medical students and we also argue that 'altruism' is not an
      observable behavior that can be measured. Instead, we suggest that medical
      educators should employ a more balanced term, borrowed from the social psychology
      literature i.e. pro-social behavior. We argue that whilst 'pro-social behavior'
      focuses on actions that benefit others, it does not do so at the expense of the
      self. In addition, it focuses on students' observable behaviors rather than their
      inner motivations, so is measurable. We conclude our article by discussing the
      formation of physicians based upon a virtue ethics, where society and the
      profession are in dialogue about the telos of medicine and its virtues, and where
      the character of the young physician is formed within the crucible of that
      dialogue. Thus, central to this pro-social behavior is the concept of phronesis
      or prudence, including the balancing of self-interest such as self-care, and the
      interests of the other.

PMID- 17530434
TI  - Non-prescription antibiotic use in Hungary.
AB  - OBJECTIVE: To estimate the extent, prevalence, and trends in non-prescription
      antibiotic use in Hungary between 2000 and 2004 at national and regional levels.
      To identify determinants of nonprescription antibiotic use. METHOD: Data on non
      prescription sales of systemic antibiotics (Anatomical Therapeutic Chemical (ATC)
      class J01) were analyzed over a five-year period. The 2004 version of the World
      Health Organisation ATC/defined daily dose (DDD) methodology was used to quantify
      antibiotic consumption. Non-prescription antibiotic sales were expressed as
      number of DDD per 1,000 inhabitants per day and as a percentage (%) of total
      antibiotic use. Further measurement units were introduced for better
      understanding of consumption and to seek an association between price,
      prescription antibiotic use, and non-prescription antibiotic use. RESULTS: During
      the study period nationwide non-prescription sales of antibiotics increased
      threefold and reached nearly 2% prevalence in 2004. Substantial interregional
      differences were detected in both the level and the share of non-prescription
      antibiotics sales. Ten drugs were responsible for 90% of non-prescription
      antibiotic sales in 2004 (doxycyline, co-amoxiclav, co-trimoxazole, penamecillin,
      ampicillin, amoxicillin, clindamycin, clarithromycin, norfloxacin, and
      cefuroxime); of these, doxycycline was the number one nonprescription antibiotic
      in all five years. A relationship was found between price and non-prescription
      antibiotic use (R = -0.732, P = 0.016). CONCLUSION: Despite the prescription-only
      status of antibiotics in Hungary, non-prescription sales occur. A further
      increase in non-prescription sales of antibiotics could be prevented by strict
      law enforcement, price augmentation, and intervention focusing on pharmacist and
      the general public. More detailed studies are needed to identify other sources
      and causes of self-medication.

PMID- 17530435
TI  - Engineered ectopic expression of the psbA gene encoding the photosystem II D1
      protein in Synechocystis sp. PCC6803.
AB  - A genetic vector-recipient system was developed to engineer expression of the
      wild-type psbA2 gene encoding the photosystem II (PSII) D1 protein only from a
      non-native location (ectopic) in the Synechocystis sp. PCC6803 and the result was
      a new strain, designated MK1. While MK1 accumulates near normal levels of PSII
      under low light conditions, it is very sensitive to photoinhibition. This
      phenotype can be traced to impaired PSII repair capacity. Based upon the
      hypothesis that the non-native transcriptional activity of the re-introduced psbA
      gene was insufficient to sustain the translation rate necessary for normal PSII
      repair rates, we conducted a quantitative analysis of the relationship between
      psbA transcript abundance on the rate of recovery from photoinhibition. Analysis
      of MK1 and two other engineered strains, with intermediate levels of psbA mRNA,
      indicated that transcript levels are indeed limiting the engineered strains.
      Furthermore, transcript levels may become limiting even in the wild-type, but
      only under very high light conditions when the demands for D1 replacement
      synthesis are maximal. The work extends the original studies of Komenda and
      colleagues (Komenda et al. (2000) Plant Mol Biol 42(4):635-645) and sets the
      stage for alternative approaches to engineering non-native expression of the D1
      protein.

PMID- 17530436
TI  - Oligomerization of thioglutamic acid: encapsulated reactions and lipid catalysis.
AB  - For cellular life to begin on the early Earth, a permeation mechanism would be
      required to allow polar solutes to enter a membrane-bounded compartment. A second
      process--internal polymerization of peptides from amino acid--would also be an
      essential step toward the first compartmented metabolic pathways leading to
      biosynthesis. Here we report a study of amino acid permeation into lipid
      vesicles, in which thioglutamic acid penetrated lipid bilayer membranes at rates
      sufficient to support internal polymerization reactions. We also investigated
      spontaneous non-enzymatic polymerization reactions of thioglutamic acid to form
      oligopeptides. We found that oligomers up to 11mers are produced in the reaction
      mixture, and conclude that certain lipid surfaces can act as catalysts in
      promoting an oligomerization reaction. These observations are pertinent to
      understanding processes by which peptide bond synthesis could take place in
      primitive cellular life on the early Earth.

PMID- 17530437
TI  - Renal Fanconi syndrome with ultrastructural defects in lysinuric protein
      intolerance.
AB  - Renal Fanconi syndrome developed rapidly in a 3-year-old Moroccan girl with
      established lysinuric protein intolerance. She was hospitalized because of
      lowered consciousness, uncoordinated movements and hepatosplenomegaly after a
      febrile period. Laboratory investigations revealed plasma ammonia 270 micromol/L
      (normal <70 micromol/L), ferritin 159 micromol/L (normal 2-59 micromol/L), LDH
      1180 U/L (normal 26-534 U/L). LPI was diagnosed based on the findings of reduced
      plasma ornithine, arginine and lysine, and an increased level of glutamine.
      Urinary orotic acid (645 micromol/mmol creatinine; normal <3.6) was strongly
      increased. A defect in the SLC7A7 amino acid transporter was established
      (homozygous c.726G > A mutation). Detailed renal function tests including an acid
      challenge test, bicarbonate loading, and tubular maximal reabsorption of glucose
      showed complex tubular dysfunction. No evidence of respiratory chain defects was
      found in muscle or kidney tissue. No morphological abnormalities were
      demonstrated in the mitochondria. Ultrastructural analysis of proximal tubular
      cells showed vacuolization and sloughing of the apical brush border (Fig. 1).
      Renal involvement in LPI has only been described in a few reports; however, no
      detailed studies of the renal acidification mechanism were performed. Our patient
      had evidence of a full-blown Fanconi syndrome. Surprisingly, a metabolic acidosis
      was found with a moderately increased serum anion gap combined with repeatedly
      normal plasma organic acid values. This finding is in contrast with the diagnosis
      of renal tubular acidosis. Patients with hyperlysinaemia have a similar heavy
      load on the renal tubules; they never develop a renal Fanconi syndrome.
      Therefore, we consider the intratubular accumulation of lysine an unlikely
      candidate for the development of the renal Fanconi syndrome.

PMID- 17530438
TI  - Arsenic trioxide induces different gene expression profiles of genes related to
      growth and apoptosis in glioma cells dependent on the p53 status.
AB  - We have previously reported that As(2)O(3) affected cell cycle progression and
      cyclins D1 and B1 expression in two glioma cell lines differing in p53 status
      (U87MG-wt; T98G-mutated). In the present study, we further demonstrated that
      As(2)O(3) affected proliferation, viability and apoptosis of the two cell lines
      in a dose- and time-dependent manner, and T98G cells were more sensitive than
      U87MG cells to As(2)O(3) -induced apoptosis and inhibition of proliferation and
      viability. We further investigated the expression profiles of genes related with
      apoptosis and cell cycle in the two cell lines with a human cDNA-microarray
      (SuperArray) spotted with 267 genes of apoptosis and cell cycle. Thirty five
      genes were upregulated and 15 genes downregulated at least 2-fold by As(2)O(3) in
      U87-MG cells; whereas, 38 genes were upregulated and 21 genes downregulated at
      least 2-fold in T98G cells by As(2)O(3). After As(2)O(3) treatment, p53
      expression was upregulated 56.5-fold in T98G cells, but only 6.0-fold in U87MG
      cells. The results indicate that As(2)O(3) suppresses the growth of U87MG cells
      mainly by regulating expression of genes of cell cycle arrest, stress and
      toxicity; whereas As(2)O(3) affects T98G cells mainly by regulating expression of
      genes belonging to Bcl-2, tumor necrotic factor receptor and ligand families. The
      data may be helpful for optimizing As(2)O(3) as an anti-cancer drug in the
      treatment of gliomas.

PMID- 17530439
TI  - Molecular cloning and characterization of 1-hydroxy-2-methyl-2-(E)-butenyl-4
      diphosphate reductase gene from Ginkgo biloba.
AB  - Ginkgo biloba contains terpene triclactones of high pharmaceutical value such as
      ginkgolides. 1-hydroxy-2-methyl-2-(E)-butenyl-4-diphosphate (HMBPP) reductase
      (HDR) is proved to be the terminal-acting enzyme in the plastid MEP pathway which
      provides isoprenoid precursors for the biosynthesis of ginkgolides. The full
      length cDNA encoding HDR, designated as GbHDR (Genbank Accession Number
      DQ364231), was isolated for the first time from G. biloba by RACE method. GbHDR
      contained a 1,422-bp open reading frame encoding 474 amino acids. The deduced
      GbHDR protein, showing high identity to HDRs of other plant species, was
      predicted to possess a chloroplast transit peptide at the N-terminal and four
      conserved cysteine residues. Two-dimensional structural analysis showed that
      GbHDR had a similar secondary structure with HDR from Arabidopsis thaliana.
      Southern blot analysis indicated that GbHDR belonged to a small gene family.
      Transcription pattern analysis revealed that GbHDR had high transcription in
      roots, and low in leaves and stems. The cloning of GbHDR gene will enable us to
      further understand the role of GbHDR involved in terpene triclatones biosynthetic
      pathway in G. biloba at molecular level.

PMID- 17530440
TI  - Cloning and sequence analysis of the gene encoding 19-kD subunit of Complex I
      from Dunaliella salina.
AB  - NADH:ubiquinone oxidoreductase (complex I ) of the mitochondrial respiratory
      chain catalyzes the transfer of electrons from NADH to ubiquinone coupled to
      proton translocation across the membrane. The cDNA sequence of Dunaliella salina
      mitochondrial NADH: ubiquinone oxidoreductase 19-kD subunit contains a 682-bp ORF
      encoding a protein with an apparent molecular mass of 19 kD. The sequence has
      been submitted to the GenBank database under Accession No. EF566890 (cDNA
      sequences) and EF566891 (genomic sequence). The deduced amino-acid sequence is
      74% identical to Chlamydomonas reinhardtii mitochondrial NADH:ubiquinone
      oxidoreductase 18-kD subunit. The 19-kD subunit mRNA expression was observed in
      oxygen deficiency, salt treatment, and rotenone treatment with lower levels. It
      demonstrate that the 19-kD subunit of Complex I from Dunaliella salina is
      regulated by these stresses.

PMID- 17530441
TI  - Molecular cloning, characterization and regulation of a peroxiredoxin gene from
      Schizosaccharomyces pombe.
AB  - A gene encoding a putative peroxiredoxin (Prx) of the fission yeast
      Schizosaccharomyces pombe was characterized and its regulation was studied. The
      full length of the prx gene was introduced into the shuttle vector pRS316 after
      PCR amplification, resulting in the recombinant plasmid pPrx10. The determined
      DNA sequence carries 1,327 bp encoding a putative Prx with a molecular mass of
      19,510 Da. Prx activity was significantly increased in the S. pombe cells
      harboring pPrx10. The accelerated growth was observed in the S. pombe/pPrx10
      cells, implying the involvement of the cloned gene in the yeast growth. To study
      transcriptional regulation of the prx gene, the prx-lacZ fusion gene was
      constructed using the yeast-E. coli shuttle vector YEp367R, and named pPrxup10.
      The synthesis of beta-galactosidase from the fusion gene was enhanced under
      carbon source-limited conditions and nitrogen starvation. Under the same growth
      conditions, the prx mRNA levels of the wild-type yeast cells were increased. The
      prx mRNA level was markedly decreased in the Pap1-negative mutant, compared with
      that in the wild-type yeast, suggesting that the basal expression of the prx gene
      is mediated by a transcription factor, Pap1. The reactive oxygen species (ROS)
      level was diminished in the S. pombe/pPrx10 cells than in the control cells. The
      extra copies of the prx gene were able to resist elevation of ROS level under
      limited carbon source condition and menadione treatment. In brief, the S. pombe
      Prx is linked with the yeast growth and up-regulated by metabolic oxidative
      stress on a transcriptional level. The Prx protein is partly responsible for
      maintaining low ROS level under normal and stressful growth conditions in the
      fission yeast.

PMID- 17530442
TI  - Induction of human UGT1A1 by a complex of dexamethasone-GR dependent on proximal
      site and independent of PBREM.
AB  - UDP-glucuronosyltransferase 1A1 (UGT1A1) plays a key role to conjugate bilirubin
      and prevent jaundice. There are two major elements for the induction of UGT1A1,
      such as PBREM (-3483/-3194), far from the promoter site, and HNF1 (-75/-63), near
      to the promoter site. In a previous report, we showed that the proximal HNF1 site
      is essential for the induction of UGT1A1 by glucocorticoid receptor (GR). In this
      report, we investigated the influence of PBREM on the induction of the UGT1A1
      reporter gene by GR and PXR with dexamethasone (DEX). We confirmed that GR was
      transferred from cytosol into the nucleus in 15-30 min by DEX stimulation, but
      HNF1 was not. We constructed a reporter gene containing PBREM to compare the
      induction of the reporter gene without PBREM by DEX-GR. The results show that
      induction of the reporter gene with PBREM by DEX at 100 muM is the same level as
      the induction of the reporter gene without PBREM, although PBREM contains GRE. Co
      transfection of hGR with the reporter gene did not show any influence of the
      induction of the reporter gene between the vector with and without PBREM.
      Meanwhile, by co-transfection of hPXR, the induction of the reporter gene with
      PBREM was significantly more than the induction of the reporter gene without
      PBREM at 100 microM DEX. This supports that hPXR induced UGT1A1 through PBREM by
      DEX. These results showed that PBREM has no relation with the induction by DEX-GR
      but the proximal site of UGT1A1 may function in stimulation by DEX-GR.

PMID- 17530443
TI  - Dual knockdown of p65 and p50 subunits of NF-kappaB by siRNA inhibits the
      induction of inflammatory cytokines and significantly enhance apoptosis in human
      primary synoviocytes treated with tumor necrosis factor-alpha.
AB  - In order to develop an anti-NF-kappaB siRNA as a novel class of anti-inflammatory
      drug, we have isolated a highly efficient siRNA targeting the p65 (RelA) subunit
      of NF-kappaB, hereafter named REL1096. To determine whether down-regulation of
      p65 by REL1096 can block the induction of inflammatory cytokines after treatment
      with tumor necrosis factor-alpha (TNF-alpha), human primary fibroblast-like
      synoviocytes were isolated from patients with rheumatoid arthritis. When treated
      with REL1096, the TNF-mediated induction of downstream target genes such as
      inflammatory cytokines, chemokines, and anti-apoptosis genes was drastically
      inhibited. To enhance the inhibitory effect of REL1096, cells were treated with
      siRNA targeting the p50 subunit of NF-kappaB together with REL1096. In addition
      to effective downregulation of inflammatory cytokines, knockdown of both p65 and
      p50 resulted in much more extensive apoptosis when compared to cells treated with
      either REL1096 or p50-siRNA alone. Thus, our results provide evidence for the
      potential use of siRNA targeting NF-kappaB as an effective means to treat
      rheumatoid arthritis. In addition to effective amelioration of synovial
      inflammation by downregulation of inflammatory cytokines, increased apoptosis by
      dual knockdown of p65 and p50 may prove advantageous in preventing invasiveness
      and destructiveness of hyperplastic synoviocytes.

PMID- 17530444
TI  - How can quality of life researchers make their work more useful to health workers
      and their patients?
AB  - To make optimal use of data from randomized trials in clinical decision-making,
      clinicians require knowledge of the magnitude of treatment effects. Reports of
      trials including quality of life data often fail to report results that provide
      interpretable estimates of magnitude of effect. Strategies that investigators
      could use to remedy this problem include reporting mean differences between
      groups in relation to the minimal important difference and reporting the
      proportion of patients who benefit from treatment and the associated number
      needed to treat. Techniques are available that allow investigators to use the
      same strategies in reporting pooled estimates from meta-analyses, even when
      studies use different instruments to measure the same construct. These reporting
      approaches, as well as ensuring access to data from individual items, will also
      help those developing decision aids to use quality of life data.

PMID- 17530445
TI  - The association of consumer expectations, experiences and satisfaction with newly
      prescribed medications.
AB  - OBJECTIVE: To examine the association between medication expectations and
      subsequent experience on treatment satisfaction and intention to continue using
      the medication. METHODS: A longitudinal study with two surveys administered to
      each patient. Patients prescribed a new medication were recruited in pharmacies
      within Michigan. Medication-related expectations were evaluated at baseline.
      Experiences, satisfaction and intent to continue were evaluated a month later.
      Analyses used included factorial ANOVA models, multiple linear regressions and
      structural equation modeling (SEM). Impact of satisfaction on intention to
      continue was evaluated using correlation analysis and SEM. RESULTS: A total of
      344 usable responses were obtained. SEM showed that expectation scores were not
      associated with both experience (path coefficient = 0.10) and satisfaction (path
      coefficient = 0.02, NS). On the other hand, experience was strongly associated
      with satisfaction (path coefficient = 0.89) and satisfaction was strongly
      associated with intent to continue using the new medication (path coefficient =
      0.81). CONCLUSIONS: This study empirically supports the value of the patient's
      experience and its contribution to satisfaction, which in turn is associated with
      intended continued use mainly due to greater effectiveness of the newly
      prescribed medication. Satisfied consumers should be more adherent, thus
      enhancing the probability of positive therapeutic outcomes.

PMID- 17530446
TI  - Factors associated with participation restriction in community-dwelling adults
      aged 50 years and over.
AB  - In the World Health Organization's International Classification of Functioning,
      Disability and Health, participation restriction--the social and personal
      consequences of health conditions and their environment--is an important
      component of the concept of disability. The cross-sectional associations between
      perceived participation restriction and health, demographic and socio-economic
      factors were examined in 7,878 community-dwelling adults aged 50 years and over
      in North Staffordshire, UK who responded to a postal survey. All health
      conditions, impairments, activity limitations, demographic and socio-economic
      factors were associated with participation restriction, after adjusting for age
      and gender in a logistic regression analysis. Health and disability factors most
      strongly and independently associated with participation restriction in a
      multivariate analysis were the number of peripheral joint pains, the number of
      health conditions, cognitive impairment, anxiety, depression, and activity
      limitation. Perceived adequacy of income, employment status and occupational
      class were also significantly associated with participation restriction after
      adjusting for health and disability factors. In conclusion, perceived
      participation restriction is associated with a range of health and socio-economic
      factors. Although further prospective research is needed to identify the
      direction of causal association, these factors represent potential targets for
      intervention to prevent or reduce participation restriction in older adults in
      the community.

PMID- 17530447
TI  - Change in health status and mortality as indicators of outcomes: comparison
      between the Medicare Advantage Program and the Veterans Health Administration.
AB  - BACKGROUND: Comparing health outcomes with adequate methodology is central to
      performance assessments of health care systems. We compared the Medicare
      Advantage Program (MAP) and the Veterans Health Administration (VHA) with regard
      to changes in health status and mortality. METHODS: We used the Death-Master-File
      for vital status and the Short-Form 36 to determine physical (PCS) and mental
      (MCS) health at baseline and at 2 years. We compared the probability of being
      alive with the same or better (than would be expected by chance) PCS (or MCS) at
      2 years and mortality, while adjusting for case-mix. Given the geographic
      variations in MAP enrollment, we did a regional sub-analysis. RESULTS: There were
      no significant differences in the probability of being alive with the same or
      better PCS except for the South (VHA 65.8% vs. MAP 62.5%, P = .0014). VHA
      patients had a slightly higher probability than MAP patients of being alive with
      the same or better MCS (71.8% vs. 70.1%, P = .002) but no significant regional
      variations. The hazard ratios for mortality in the MAP were higher than in the
      VHA across all regions. CONCLUSION: With the use of appropriate methodology, we
      found small differences in 2-year health outcomes that favor the VHA.

PMID- 17530448
TI  - Patient-reported outcomes measurement and management with innovative
      methodologies and technologies.
AB  - Successful integration of modern psychometrics and advanced informatics in
      patient-reported outcomes (PRO) measurement and management can potentially
      maximize the value of health outcomes research and optimize the delivery of
      quality patient care. Unlike the traditional labor-intensive paper-and-pencil
      data collection method, item response theory-based computerized adaptive testing
      methodologies coupled with novel technologies provide an integrated environment
      to collect, analyze and present ready-to-use PRO data for informed and shared
      decision-making. This article describes the needs, challenges and solutions for
      accurate, efficient and cost-effective PRO data acquisition and dissemination
      means in order to provide critical and timely PRO information necessary to
      actively support and enhance routine patient care in busy clinical settings.

PMID- 17530449
TI  - Enhancing measurement in health outcomes research supported by Agencies within
      the US Department of Health and Human Services.
AB  - Many of the Institutes, Agencies and Centers that make up the US Department of
      Health and Human Services (DHHS) have recognized the need for better
      instrumentation in health outcomes research, and provide support, both internally
      and externally, for research utilizing advances in measurement theory and
      computer technology (informatics). In this paper, representatives from several
      DHHS agencies and institutes will discuss their need for better instruments
      within their discipline and describe current or future initiatives for exploring
      the benefits of these technologies. Together, the perspectives underscore the
      importance of developing valid, precise, and efficient measures to capture the
      full burden of disease and treatment on patients. Initiatives, like the Patient
      Reported Outcomes Measurement Information System (PROMIS) to create health
      related quality of life item banks, represent a trans-DHHS effort to develop a
      standard set of measures for informing decision making in clinical research,
      practice, and health policy.

PMID- 17530450
TI  - Developing tailored instruments: item banking and computerized adaptive
      assessment.
AB  - Item banks and Computerized Adaptive Testing (CAT) have the potential to greatly
      improve the assessment of health outcomes. This review describes the unique
      features of item banks and CAT and discusses how to develop item banks. In CAT, a
      computer selects the items from an item bank that are most relevant for and
      informative about the particular respondent; thus optimizing test relevance and
      precision. Item response theory (IRT) provides the foundation for selecting the
      items that are most informative for the particular respondent and for scoring
      responses on a common metric. The development of an item bank is a multi-stage
      process that requires a clear definition of the construct to be measured, good
      items, a careful psychometric analysis of the items, and a clear specification of
      the final CAT. The psychometric analysis needs to evaluate the assumptions of the
      IRT model such as unidimensionality and local independence; that the items
      function the same way in different subgroups of the population; and that there is
      an adequate fit between the data and the chosen item response models. Also,
      interpretation guidelines need to be established to help the clinical application
      of the assessment. Although medical research can draw upon expertise from
      educational testing in the development of item banks and CAT, the medical field
      also encounters unique opportunities and challenges.

PMID- 17530451
TI  - Development of a validation protocol to determine the ability of screw-top
      containers to be watertight and to withstand impact damage from accidental
      dropping.
AB  - Polypropylene screw-top containers are used to collect, transport and store a
      variety of tissues within tissue banks. These containers are validated for use by
      tissue banks but no standard validation protocol is used. We present here a
      protocol for testing screw-top containers for leakage, evaporation and the
      ability to withstand accidental impact damage. Three different containers were
      tested, MedFor S072, MedFor S277 and MacoPharma PROT0483. The validation can
      detect differences between different manufacturer's containers and this protocol
      will be used in future validations of screw-top containers within National Blood
      Service Tissue Services.

PMID- 17530452
TI  - Delivering cancer genetics services--new ways of working.

PMID- 17530453
TI  - Tying SUMO modifications to dynamic behaviors of chromosomes during meiotic
      prophase of Saccharomyces cerevisiae.
AB  - In budding yeast Saccharomyces cerevisiae, centromeres and telomeres are tethered
      to the nuclear envelope during premeiotic interphase. Immediately after cells
      enter meiotic prophase, chromosomes undergo global reorganization, including
      bouquet formation (telomere clustering), non-homologous centromere coupling,
      homologous pairing, and assembly/disassembly of synaptonemal complexes. These
      chromosome dynamics have been implicated in promoting pairing, synapsis,
      crossover DNA recombination and segregation between homologous chromosomes. This
      review discusses recent studies related to the role of small ubiquitin-like
      modifier (SUMO) modification in controlling the overall budding yeast chromosome
      dynamics during meiotic prophase.

PMID- 17530454
TI  - A versatile 3D reconstruction system of the spine and pelvis for clinical
      assessment of spinal deformities.
AB  - This paper presents a three-dimensional (3D) reconstruction system of the human
      spine for the routine evaluation of musculoskeletal pathologies like idiopathic
      scoliosis. The main objective of this 3D reconstruction system is to offer a
      versatile and robust tool for the 3D analysis of spines in any healthcare centre
      with standard clinical setup using standard uncalibrated radiographic images. The
      novel system uses a self-calibration algorithm and a weak-perspective method to
      reconstruct the 3D coordinates of anatomical landmarks from bi-planar
      radiographic images of a patient's trunk. Additionally, a small planar object of
      known dimensions is proposed to warrant an accurately scaled model of the spine.
      In order to assess the validity of the 3D reconstructions yielded by the proposed
      system, a clinical study using 60 pairs of digitized X-rays of adolescents was
      conducted. The subject cohort in the study group was composed of 51 scoliotic and
      9 non-scoliotic patients, with an average Cobb angle on the frontal plane of 25
      degrees. For each case, a 3D reconstruction of the spine and pelvis was obtained
      with the previous system used at our hospital (which requires a positioning
      apparatus and a calibration jacket), and with the proposed method. Results show
      that 3D reconstructions obtained with the new system using uncalibrated X-ray
      images yield geometrically accurate models with insignificant differences for 2D
      and 3D clinical indexes commonly used in the evaluation of spinal deformities.
      This demonstrates the system to be a viable and accurate tool for clinical
      studies and biomechanical analysis purposes, with the added advantage of
      versatility to any clinical setup for routine follow-ups and surgical planning.

PMID- 17530456
TI  - Cold face test: adrenergic phase.
AB  - The cold face test (CFT) evokes reflex bradycardia and pressor responses.
      Bradycardia has been used to assess vagal function. This study evaluated two
      aspects of physiology and clinical applicability of the pressor response. During
      constant monitoring of blood pressure (Finapres) and heart rate (EKG), CFT was
      induced by the application of three cold packs (0.5 degrees C) to the face for 1
      min. Group 1: Latencies of systolic blood pressure (SBP) and heart rate (HR)
      response to the CFT were recorded in 10 normal subjects. Group 2: CFT was
      performed in eight normal subjects after cholinergic blockade with atropine (0.03
      mg/kg body weight intravenously). Group 3: Four patients with baroreflex failure
      and five patients with pure autonomic failure were subjected to CFT. In Group 1,
      mean latency of CFT-induced SBP rise (mean +/- SD) (13.8 +/- 16.6 s) was longer
      than that of bradycardia (5.6 +/- 4.6 s). In Group 2, bradycardia was abolished
      in all subjects and SBP was unaffected after atropine administration. In Group 3,
      patients with baroreflex failure demonstrated normal HR and SBP responses to CFT.
      In the pure autonomic failure patients, bradycardia was absent and SBP response
      was either absent or subnormal. The adrenergic phase of the CFT is independent of
      the cholinergic phase (bradycardia) and baroreceptors. Rise in SBP is useful in
      evaluating the integrity of the efferent sympathetic pathway with baroreflex
      failure. Absence of SBP rise in response to the CFT may be of diagnostic value in
      detecting the sympathetic component of pure autonomic failure.

PMID- 17530457
TI  - Effect of dimenhydrinate on autonomic activity in humans.
AB  - The purpose of this study was to examine the effect of dimenhydrinate on resting
      muscle sympathetic nerve activity (MSNA), the vestibulosympathetic reflex, and
      the baroreflexes. Sixteen subjects participated in two double-blinded studies
      that measured mean arterial pressure (MAP), heart rate (HR), and MSNA responses
      before and after oral administration of dimenhydrinate (100 mg) or a placebo. In
      study one, 3 min of head-down rotation (HDR) was performed to engage the otolith
      organs. Dimenhydrinate (n = 10) did not alter resting MSNA, MAP, or HR. HDR
      increased MSNA before (Delta5 +/- 1 bursts/min; P < 0.01) and after (Delta4 +/- 1
      bursts/min; P < 0.01) drug administration, but these responses were not different
      from the placebo (n = 6). In study two, 4 min of lower body negative pressure
      (LBNP) at -30 mmHg was performed. During the third min of LBNP, HDR was
      performed. MSNA increased during the first 2 min of LBNP before (Delta13 +/- 2
      bursts/min; P < 0.01) and after (Delta14 +/- 2 bursts/min; P < 0.01)
      dimenhydrinate. HDR combined with LBNP increased MSNA further during the third
      min of LBNP (Delta18 +/- 2 bursts/min before and Delta17 +/- 2 bursts/min after
      dimenhydrinate; P < 0.01). These responses were not significantly different from
      the placebo. In contrast, HR responses to LBNP during the dimenhydrinate trial
      were increased when compared to all other trials (Delta5 +/- 1 beats/min; P <
      0.01). These results indicate that dimenhydrinate augments heart rate responses
      to baroreceptor unloading, but does not alter resting MSNA, the sympathetic
      baroreflexes, or the vestibulosympathetic reflex.

PMID- 17530458
TI  - Heart rate variability in children with idiopathic ventricular tachycardia.
AB  - Idiopathic ventricular tachycardia (IVT) is a rare arrhythmia in children. A
      great deal of uncertainty and numerous questions still remain regarding the
      extent of investigation, therapy, and long-term prognosis for children with IVT.
      The existence of subclinical cardiac disease, as well as of autonomic dysfunction
      in patients with ventricular arrhythmias, has been well documented. A number of
      experimental and clinical studies have suggested that imbalances within the
      cardiac autonomic system's activity may be crucial in the generation of
      ventricular tachycardia, irrespective of the presence of cardiovascular
      pathological substrate. Heart rate variability (HRV) analysis provides a useful
      method for measuring the autonomic activity. This study evaluates HRV in children
      with IVT. The study included 31 children with ventricular arrhythmia who were
      divided into two groups: (1) patients with frequent ventricular extrasystoles
      (VES) and (2) patients with IVT. The control group comprised 23 healthy children
      without pathological findings on 24-h ECG Holter. Twenty-four-hour ambulatory
      electrocardiography recordings were obtained, and the time-domain variables were
      calculated. HRV was compared to age-related normal values. It was observed that
      the overall heart rate variability is diminished in children with IVT. We
      recommend HRV analysis of any child with IVT. Quantification of the autonomic
      nervous system activity using time domain analyses may be a helpful diagnostic
      tool in the clinical assessment and initial evaluation of these children.

PMID- 17530459
TI  - Characterization of novel orange fluorescent protein cloned from cnidarian tube
      anemone Cerianthus sp.
AB  - A novel orange fluorescent protein (OFP) was cloned from the tentacles of
      Cnidarian tube anemone Cerianthus sp. It consists of 222 amino acid residues with
      a calculated molecular mass of 25.1 kDa. A BLAST protein sequence homology search
      revealed that native OFP has 81% sequence identity to Cerianthus membranaceus
      green fluorescent protein (cmFP512), 38% identity to Entacmaea quadricolor red
      fluorescent protein (eqFP611), 37% identity to Discosoma red fluorescent protein
      (DsRed), 36% identity to Fungia concinna Kusabira-orange fluorescent protein
      (KO), and a mere 21% identity to green fluorescent protein (GFP). It is most
      likely that OFP also adopts the 11-strand beta-barrel structure of fluorescent
      proteins. Spectroscopic analysis indicated that it has a wide absorption spectrum
      peak at 548 nm with two shoulders at 487 and 513 nm. A bright orange fluorescence
      maximum at 573 nm was observed when OFP was excited at 515 nm or above. When OFP
      was excited well below 515 nm, a considerable amount of green emission maximum at
      513 nm was also observed. It has a fluorescence quantum yield (Phi) of 0.64 at 25
      degrees C. The molar absorption coefficients (epsilon) of folded OFP at 278 and
      548 nm are 47,000 and 60,000 M(-1) x cm(-1), respectively. Its fluorescent
      brightness (epsilon Phi) at 25 degrees C is 38,400 M(-1) x cm(-1). Like other
      orange-red fluorescent proteins, OFP is also tetrameric. It was readily expressed
      as soluble protein in Escherichia coli at 37 degrees C, and no aggregate was
      observed in transfected HeLa cells under our experimental conditions. Fluorescent
      intensity of OFP is detectable over a pH range of 3 to 12.

PMID- 17530460
TI  - Prevention of glutamate excitotoxicity in motor neurons by 5,6-dihydrocyclopenta
      1,2-dithiole-3-thione: implication to the development of neuroprotective drugs.
AB  - Glutamate-induced excitotoxicity and oxidative damage are believed to play an
      important role in the development of a number of central nerve system disorders.
      Nuclear-factor erythroid 2-related factor 2 (Nrf2) is a master transcriptional
      regulator of many cytoprotective genes. We report herein that 5,6
      dihydrocyclopenta-1,2-dithiole-3-thione (CPDT), which was previously shown to
      induce several Nrf2 target genes in non-nervous cells and tissues, significantly
      activates Nrf2 and Nrf2 target genes in rat spinal cord explants. More
      importantly, such activation is accompanied by complete inhibition of glutamate
      induced motor neuron death in these explants. Further studies show that CPDT
      inhibits glutamate-induced intracellular Ca(2+) rise, loss of mitochondrial
      transmembrane potential and depletion of tissue glutathione. CPDT did not appear
      to modulate glutamate transport or to interfere with glutamate interaction with
      postsynaptic receptors. Taken together, our studies have identified CPDT as a
      promising neuroprotective agent and suggest that pharmacological activation of
      Nrf2 signaling is an important strategy for protection against glutamate-induced
      excitotoxicity.

PMID- 17530461
TI  - RANKL, RANK, osteoprotegerin: key partners of osteoimmunology and vascular
      diseases.
AB  - 1997 saw the identification of a novel set of proteins within the tumor necrosis
      factor (TNF)/TNF receptor families that are required for the control of bone
      remodeling. Therefore, these receptors, receptor activator of nuclear factor
      kappa B (RANK), osteoprotegerin (OPG) and their ligand RANK ligand (RANKL) became
      the critical molecular triad controlling osteoclastogenesis and pathophysiologic
      bone remodeling. However, the establishment of the corresponding knock-out and
      transgenic mice revealed unexpected results, most particularly, the involvement
      of these factors in the vascular system and immunity. Thus, the OPG/RANK/RANKL
      molecular triad appears to be associated with vascular calcifications and plays a
      pivotal function in the development of the immune system through dendritic cells.
      OPG/RANK/RANKL thus constitute a molecular bridge spanning bone metabolism,
      vascular biology and immunity. This review summarizes recent knowledge of
      OPG/RANK/RANKL interactions and activities as well as the current evidence for
      their participation in osteoimmunology and vascular diseases. In fine, the
      targeting of the OPG/RANK/RANKL axis as novel therapeutic approaches will be
      discussed.

PMID- 17530462
TI  - Coronavirus envelope protein: a small membrane protein with multiple functions.
AB  - Coronavirus envelope protein is a small membrane protein and minor component of
      the virus particles. It plays important roles in virion assembly and
      morphogenesis, alteration of the membrane permeability of host cells and virus
      host cell interaction. Here we review recent progress in characterization of the
      biochemical properties, membrane topology and functions of the protein.

PMID- 17530463
TI  - Glycogen synthase kinase 3: a key regulator of cellular fate.
AB  - The serine/threonine kinase glycogen synthase kinase-3 (GSK-3) was initially
      identified as a key regulator of insulin-dependent glycogen synthesis. GSK-3 was
      subsequently shown to function in a wide range of cellular processes including
      differentiation, growth, motility and apoptosis. Aberrant regulation of GSK-3 has
      been implicated in a range of human pathologies including Alzheimer's disease,
      non-insulin-dependent diabetes mellitus (NIDDM) and cancer. As a consequence, the
      regulation of GSK-3 and the therapeutic potential of GSK-3 inhibitors have become
      key areas of investigation. This review will focus on the mechanisms of GSK-3
      regulation, with emphasis on modulation by upstream signals, control of substrate
      specificity and GSK-3 localisation. The details of these mechanisms will be
      discussed in the context of specific signalling pathways.

PMID- 17530464
TI  - SUMO and NF-kappaB ties.
AB  - Members of the NF-kappaB family of transcription factors play critical roles in
      regulating immunity and cell survival and contribute to cancer progression and
      chemoresistance. Over the past 20 years, much has been learned about the
      remarkable complexity in regulation of NF-kappaB signaling. In particular, recent
      studies have added to our current understanding of the roles of a multitude of
      posttranslational modifications in this signaling system: these include
      phosphorylation, acetylation, nitrosylation, ubiquitination, neddylation and
      sumoylation. This review will highlight our current knowledge of the roles of
      sumoylation in regulating NF-kappaB signaling and functions and will address
      future perspectives.

PMID- 17530465
TI  - Effect of body mass index on Argatroban therapy during percutaneous coronary
      intervention.
AB  - BACKGROUND: Obesity is common in patients undergoing percutaneous coronary
      intervention (PCI). Argatroban, a direct thrombin inhibitor, is used during PCI
      in patients with or at risk of heparin-induced thrombocytopenia (HIT) and also
      has been evaluated in conjunction with glycoprotein IIb/IIIa inhibition in nonHIT
      patients. We investigated the effect of body mass index (BMI), and specifically
      obesity (BMI>30 kg/m2), on argatroban therapy during PCI. METHODS: From
      previously reported studies of argatroban therapy during PCI in patients with or
      at risk of HIT (ie, HIT group) or in conjunction with glycoprotein IIb/IIIa
      inhibition (ie, nonHIT group), we identified patients with sufficient data to
      determine BMI. After an initial bolus of 350 microg/kg (HIT group) or 300 or 250
      microg/kg (nonHIT group), patients received continuous argatroban 25-30
      microg/kg/min (adjusted to achieve ACTs of 300-450 s, HIT group) or 15
      microg/kg/min (target ACTs of 275-325 s, nonHIT group) during PCI, with
      additional 150 microg/kg boluses allowed if needed. Regression analyses evaluated
      relationships between patient BMI and ACT response to initial bolus
      administration, mean infusion dose (HIT group only), and rate of ACT decline
      after PCI. Frequencies of additional bolus usage and clinical outcomes were
      compared between obese and nonobese patients. RESULTS: Our analysis population
      included 225 patients (85 obese) in total: 73 in the HIT group and 152 in the
      nonHIT group (300 microg/kg bolus, n=101; 250 microg/kg bolus, n=51), with BMIs
      of 16.3-50.9 kg/m2. No association was detected between BMI and the first ACT
      after bolus administration (median ACTs of 361, 298, and 289 s, respectively,
      following 350, 300, and 250 microg/kg bolus), mean infusion dose (24.2+/-4.9
      microg/kg/min overall in HIT group), or time to ACTs<or=160 s after argatroban
      cessation (median 4.4 h in HIT group and 1.7-2.1 h in nonHIT group). Fifteen (5
      obese) patients in the HIT group and 36 (13 obese) in the nonHIT group required
      additional boluses, without differences by obesity versus nonobesity (P>or=0.35).
      Clinical outcomes did not differ (P>or=0.09) between obese and nonobese
      individuals: 4 (3 obese) patients in the HIT group and 4 (2 obese) in the nonHIT
      group had ischemic complications; 1 nonobese patient in the HIT group and 2 (1
      obese) in the nonHIT group experienced major bleeding. CONCLUSIONS: These
      findings support the use of actual body weight-adjusted (and ACT-targeted)
      argatroban therapy during PCI and suggest that dose adjustment for obesity (BMI
      up to 50.9 kg/m2) is unnecessary.

PMID- 17530466
TI  - The clinical and immunogenetic characteristics of adult-onset type 1 diabetes
      mellitus in Korea.
AB  - Although the HLA class II alleles and immunological abnormalities are associated
      with type 1 diabetes mellitus (T1DM) in all racial groups, there are considerable
      variations in the genotypes and the prevalence of autoantibodies. In order to
      investigate the characteristics of the immunogenetic patterns and to use these as
      an early diagnostic tool and guideline for a therapeutic plan, we examined the
      clinical characteristics and the patterns of anti-GAD antibody (GADA), IA-2
      antibody (IA-2A), HLA-DR and HLA-DQ in Korean adult-onset T1DM patients. Adult
      onset patients had higher serum C-peptide levels than child-onset patients. In
      adult-onset patients, the prevalence of GADA and IA-2A were 59.5% and 15.3%
      respectively, and increased frequencies of HLADR4 and-DR9 were found. The
      frequencies of HLADQA1,-DQB1 and-DQ heterodimers were similar to those of the
      control, but child-onset patients had high frequencies of the HLA-DR3,-DR4,-DR9,
      DQA1*0301, DQA1*0501 and DQB1*0201 genotypes. In conclusion, Korean adult-onset
      T1DM patients had a lower prevalence of GADA, which was comparable to that found
      in Caucasian patients. The detection of GADA might help to predict the insulin
      dependency of adult-onset diabetes. Difference in the frequencies of diabetes
      associated with HLA type suggests that there might be a heterogeneity in the
      pathogenesis of diabetes according to the age of onset.

PMID- 17530467
TI  - HbA1c levels are better predicted by prebreakfast than postbreakfast blood
      glucose self-analyses in type 2 diabetes. Influence of duration of diabetes and
      mode of treatment.
AB  - The present study aimed at assessing the capability of both prebreakfast and
      postbreakfast home blood glucose self-analyses to predict HbA1c in type 2
      diabetic individuals and the influence of duration of diabetes or mode of
      treatment in this regard. Two hundred and twenty-seven type 2 diabetic
      individuals consecutively attending our diabetes clinic between January 2000 and
      December 2002 (42.3% placed on oral drugs and 57.7% receiving insulin therapy,
      either alone or as a combination with oral drugs) were retrospectively selected
      and three more recent values regarding both home prebreakfast and one-hour
      postbreakfast blood glucose self-analyses were averaged. Patients were classified
      by their mode of treatment (submission or not to insulin therapy) and by quartile
      of duration of diabetes. The correlations of HbA1c levels with either
      prebreakfast or postbreakfast blood glucose self-analyses were performed in the
      whole group and in every subset considered. HbA1c values had a stronger
      correlation with prebreakfast blood glucose self-analyses (r=0.53, p<0.001) than
      with one-hour postbreakfast home glucose self-analyses (r=0.39, p<0.001).
      Prebreakfast (but not onehour postbreakfast) blood glucose self-analysis was
      selected as independently associated to HbA1c levels in a multiple regression
      analysis performed upon the whole study group as well as in most of the subsets
      considered. HbA1c values had a stronger correlation with prebreakfast glucose
      self-analyses in individuals with a shorter duration of diabetes (r=0.71,
      p<0.001) and not submitted to insulin therapy (r=0.59, p<0.001). Increasing age
      characterised individuals with the highest postbreakfast glucose excursions (one
      way ANOVA, p<0.01). These data suggest that prebreakfast blood glucose self
      analyses are more closely related to HbA1c levels than one-hour postbreakfast
      blood glucose self-analyses in most of the clinical spectrum of type 2 diabetes
      mellitus.

PMID- 17530468
TI  - The effect of TRAIL molecule on cell viability in in vitro beta cell culture.
AB  - Insulin-dependent diabetes mellitus (IDDM) is an organ-specific autoimmune
      disorder triggered by autoreactive T cells directed to pancreas beta-cell
      antigens. In this disorder, more than 90% of beta cells are destroyed. Cell death
      may be mediated via soluble or membrane-bound cell death ligands. One of these
      ligands may be tumour necrosis factor (TNF)-related apoptosis-inducing ligand
      (TRAIL), a member of the TNF-alpha superfamily. In the present study, we examined
      whether TRAIL had cytotoxic effects on adult rat pancreas beta cell cultures and
      INS1-E rat insulinoma cell line cultures or not. In this study, cell destruction
      models were built with TRAIL concentrations of 10, 100 and 1000 ng. 3-(4,5
      Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test was used for
      evaluating cell viability. It was detected that cell cultures with TRAIL added
      showed no differences statistically when compared with control cultures
      containing no toxic additions. These results showed that TRAIL did not have
      significant cytotoxic effects on pancreas beta cell culture and INS-1E rat
      insulinoma cell line cultures. Detection of the expression of TRAIL receptors and
      natural apoptosis inhibitor proteins will be favourable to investigate the
      resistance mechanisms to TRAIL-induced cell death in this cell culture system.

PMID- 17530469
TI  - Short-term therapy with atorvastatin or fenofibrate does not affect plasma
      ghrelin, resistin or adiponectin levels in type 2 diabetic patients with mixed
      hyperlipoproteinaemia.
AB  - Lipid-lowering therapy is associated with reduced cardiovascular risk. The aim of
      the present study was to investigate whether lipid-lowering therapy might be
      associated with changes in the concentrations of metabolically important hormone
      concentrations. We performed a randomised cross-over open-label trial with
      atorvastatin (10 mg/day) and fenofibrate (200 mg/day), each for 6 weeks separated
      by a 6-week washout period in 13 patients (5 men, 8 women, age 60.0+/-6.8 years,
      body mass index 30.0+/-3.0 kg/m2) with type 2 diabetes mellitus and mixed
      hyperlipoproteinaemia. Plasma ghrelin (RIA, Phoenix Pharmaceuticals, Mountain
      View, CA, USA), adiponectin (ELISA, Biovendor, Heidelberg, Germany) as well as
      resistin (ELISA, Linco Research, St. Charles, MO, USA) concentrations were
      measured before and after atorvastatin as well as before and after fenofibrate.
      Ghrelin (462+/-84 pg/ml before vs. 464+/-102 pg/ml after atorvastatin, n.s.;
      454+/-85 pg/ml before vs. 529+/-266 pg/ml after fenofibrate, n.s.), resistin
      (24.4+/-7.4 pg/ml before vs. 23.7+/-9.1 pg/ml after atorvastatin, n.s.; 23.4+/
      8.2 pg/ml before vs. 19.9+/-5.5 pg/ml after fenofibrate, n.s.), adiponectin
      (10.89+/-5.33 pg/ml before vs. 12.41+/-5.75 pg/ml after atorvastatin, n.s.;
      12.58+/-9.87 pg/ml before vs. 10.27+/-5.23 pg/ml after fenofibrate, n.s.) and
      insulin levels did not change significantly during lipid-lowering therapy. In
      patients with type 2 diabetes and mixed hyperlipoproteinaemia, short-term
      atorvastatin as well as fenofibrate therapy had no significant effects on
      adiponectin, ghrelin or resistin levels.

PMID- 17530470
TI  - The influence of homocysteine levels on endothelial function and their relation
      with microvascular complications in T2DM patients without macrovascular disease.
AB  - The aim of this study was to investigate the influence of homocysteine (hcy)
      levels on endothelial function by the method of brachial artery ultrasonography
      and their relation with microvascular complications in type 2 diabetes mellitus
      (T2DM) patients without macrovascular disease. Fifty-nine T2DM patients with a
      mean age of 53.4+/-8.6 years and diabetes duration of 8.1+/-6.2 years and 16
      healthy controls with a mean age of 47+/-14.5 years were included in the study.
      Endothelialdependent and endothelium-independent flow-mediated dilatation (FMD)
      were evaluated via brachial artery ultrasonography. Fasting plasma glucose (FPG),
      glycosylated haemoglobin (A1c), lipid profile, hcy, B12 and folic acid levels
      were measured. Diabetic patients and control group individuals were compared with
      regard to the laboratory values and brachial artery vascular reactivity. Factors
      influencing endothelium-dependent FMD were investigated with linear regression
      analysis. Age, gender, body mass index, lipid profiles and hcy levels were
      similar in both groups (p>0.05). Endothelium-dependent FMD percentages were
      significantly lower in diabetics than in the control group (7.7+/-5.9 vs. 11.7+/
      7.1%, p<0.05). Endothelial-independent FMD percentage was similar for both groups
      (p>0.05). The upper limit of the reference hcy value was found to be 12.6
      micromol/l in the control group. In the diabetic group, hcy levels were high in
      33 patients and normal in 26 patients. No difference was detected between the
      patients with high hcy levels and those with a normal level with regard to
      endothelium-dependent and endothelium-independent FMD values (p>0.05). Mean hcy
      levels were 16+/-1.7 and 13.3+/-4.3 micromol/l in T2DM patients with
      microvascular complication and those with no microvascular complication,
      respectively (p<0.05). Regression analysis revealed that the main factors
      influencing the endothelial-dependent FMD were FPG, total cholesterol (TC),
      triglycerides (TG) and high-density lipoprotein (HDL-C) levels (p<0.05, p=0.05,
      p=0.05, p=0.02, respectively). Hcy, folic acid and B12 values did not influence
      endothelium-dependent FMD (p>0.05). Diabetes duration and A1c levels were close
      to being significant although they did not reach statistical significance (p=0.07
      and p=0.08 respectively). Hcy levels have no effect on endothelium-dependent and
      endothelium-independent FMD in T2DM patients without macrovascular complications.
      The influence of classical atherogenic factors (such as FPG, TC, TG and HDL-C
      levels) on endothelium functions, detected with endothelium-dependent FMD, is
      greater.

PMID- 17530471
TI  - Lovastatin effects on bone mineral density in postmenopausal women with type 2
      diabetes mellitus.
AB  - The objective of this study was to examine the effects of lovastatin on bone
      mineral density (BMD) of postmenopausal women with type 2 diabetes mellitus (DM).
      The study was an open-label clinical trial conducted from March 2002 to November
      2003. Fifty-five postmenopausal women age 54-67 years with type 2 DM were
      allocated to lovastatin-treated and control (without lovastatin) groups based on
      low-density lipoprotein cholesterol (LDL-C) >130 or < or =130 mg/dl. The first
      group received lovastatin (20 mg daily titrated every 3 months to keep LDL-C less
      than 130 mg/dl) for a total of 18 months. The second group received their own
      diabetic regimen without statin. The BMD of the lumbar spine (L1 - L4), femoral
      neck, Wards triangle, trochanter and total hip was measured by dual-energy X-ray
      absorptiometry at baseline and after 18 months. In the 28 women treated with
      lovastatin, the BMD increased in lumbar spine (from 0.946 (0.122) to 0.978
      (0.135) g/cm2, p<0.01) and Ward's triangle (from 0.685 (0.123) to 0.780 (0.186)
      g/cm2, p<0.01). In the 27 women not treated with statin, the changes in BMD at
      all bone sites were not statistically significant. BMD was higher in femoral neck
      (1.2% vs. -2.7%, p<0.05), Ward's triangle (13.9% vs. 3.3%, p<0.05), trochanter (
      0.1% vs. -2.9%, p<0.05), total hip (1.2% vs. -1.4%, p<0.05) and lumbar spine
      (3.4% vs. 1.2%, p>0.05) at the end of the study. Treatment with lovastatin may
      prevent bone loss in postmenopausal women with type 2 DM.

PMID- 17530472
TI  - L-Carnitine inhibits protein glycation in vitro and in vivo: evidence for a role
      in diabetic management.
AB  - Glycation-initiated changes in tissue proteins are suggested to play an important
      role in the development of diabetes-related pathological changes. The purpose of
      this study was to examine the anti-glycating effect of L-carnitine (CA) in vivo
      in the high-fructose diet-fed rat and to determine the potential of CA to inhibit
      in vitro glycation. Additionally the glucose-disposal efficiency of CA in the rat
      diaphragm was investigated. High-fructose diet (60 g/100 g diet)-fed rats were
      treated with CA (300 mg/kg/day i.p.) for 60 days. The effect of CA on glucose,
      fructose and fructosamine in plasma, methyl glyoxal and glycated haemoglobin in
      whole blood and skin and tail tendon collagen glycation were determined. The
      inhibitory effect of CA on the glycation of bovine serum albumin in vitro was
      compared with that of aminoguanidine (AG), a known antiglycation agent. Glucose
      utilisation induced by insulin in the control rat diaphragm was monitored in the
      presence and absence of CA. High-fructose feeding induced hyperglycaemia and
      glycation of haemoglobin and skin and tail tendon collagen. In CA-administered
      fructose-fed rats glycation was significantly reduced. In vitro glycation and
      accumulation of advanced glycation end products were mitigated by CA. CA was more
      effective than AG in inhibiting glycation in vitro. CA also enhanced the
      utilisation of glucose in the rat diaphragm. The findings of the study reveal
      that CA not only has antiglycation effect but also enhances glucose disposal in
      the rat diaphragm. These findings provide evidence for the therapeutic utility of
      CA in diabetes and associated complications.

PMID- 17530473
TI  - NT-pro-BNP measured at discharge predicts outcome in multimorbid diabetic
      inpatients with a broad spectrum of cardiovascular disease.
AB  - The prognostic value of NT-pro-BNP has not been thoroughly evaluated in diabetic
      inpatients with manifest cardiovascular disease. NT-pro-BNP was measured in 156
      patients with type 2 diabetes mellitus hospitalised due to cardiovascular
      disease. The association of NT-pro-BNP with mortality and the combined endpoint
      (CE) of death, heart failure decompensation, stroke and myocardial infarction was
      analysed during a median follow-up time of 1183 days. Patients who died (1669 IQR
      788-5640 vs. 398, IQR 158-990 pg/ml) and patients with CE (1353, IQR 730-4289 vs.
      304, IQR 128-784 pg/ml, both p=0.0001) had significantly elevated NT-pro-BNP
      compared to patients without the corresponding endpoint. Patients with
      supramedian NT-pro-BNP (>518 pg/ml) had significantly worse outcome regarding
      mortality (HR 5.5, 95%CI 2.0-14.8) and CE (HR 5.0, 95%CI 2.2-11.2) than patients
      with inframedian values even after adjustment for age, NYHA class and renal
      function. At a cut-off of 422 pg/ml, NT-pro-BNP showed a sensitivity of 89.6% and
      a negative predictive value of 92.8% for detection of patients with future CE. In
      this sample of diabetic patients with a broad spectrum of cardiovascular disease,
      NT-pro-BNP was a strong predictor of long-term outcome. NT-pro-BNP measured at
      discharge identifies high-risk patients independently of the underlying heart
      disease.

PMID- 17530474
TI  - Pharmacological and behavioral determinants of cocaine, methamphetamine, 3,4
      methylenedioxymethamphetamine, and para-methoxyamphetamine-induced hyperthermia.
AB  - RATIONALE: Cocaine, methamphetamine, 3,4-methylenedioxymethamphetamine (MDMA,
      ecstasy), and para-methoxyamphetamine (PMA) disrupt normal thermoregulation in
      humans, with PMA being associated with more severe cases of hyperthermia. Harm
      minimization advice on how to prevent overheating depends on appropriate
      thermoregulatory behavior by drug users. OBJECTIVES: The purpose of the current
      study was to establish dose-response relationships for the effects of a number of
      commonly used illicit stimulants and investigate the behavioral response to
      increased core temperature. MATERIALS AND METHODS: Sprague-Dawley rats with
      telemetry implants were administered either saline or 4, 12, 26, 40 or 80
      micromol/kg of cocaine, methamphetamine, MDMA, or PMA and confined to an ambient
      temperature of 30 degrees C for 30 min, before being able to choose their
      preferred temperature on a thermally graded runway (11-41 degrees C). RESULTS:
      The increased core temperature caused by administration of cocaine,
      methamphetamine, and MDMA treatment led to the animals seeking the cool end of
      the runway to correct their core temperature, although this did not occur in PMA
      treated rats. The order of potency for increasing core temperature was
      methamphetamine >PMA = MDMA>cocaine. This differed to the slopes of the dose
      response curves where MDMA and PMA showed the steepest slope for the doses used
      followed by methamphetamine then cocaine. CONCLUSIONS: These results suggest that
      behavioral aspects of thermoregulation are important in assessing the potential
      of individual drugs to cause harmful increases in core temperature.

PMID- 17530475
TI  - The nicotinic acetylcholine receptor antagonist mecamylamine prevents escalation
      of cocaine self-administration in rats with extended daily access.
AB  - RATIONALE: Escalation from moderate to excessive drug intake is a hallmark of
      human addiction that can be modeled in rats by giving them longer daily access
      time to self-administer cocaine. Nicotine and cocaine are commonly coabused drugs
      in humans and recent work in animals suggests that activation of nicotinic
      acetylcholine receptors (nAChR) can increase cocaine self-administration.
      OBJECTIVES: Determine the role of nAChR in the escalation of cocaine self
      administration. METHODS: Control rats self-administered cocaine (0.75
      mg/kg/infusion) for either 1 or 6 h per day. Experimental groups had the nAChR
      antagonist mecamylamine (MEC) added to the cocaine solution for 5 days after the
      transition from short (1 h per day) to long access (6 h per day) for cocaine self
      administration. After 5 days, MEC was removed from the cocaine solution. RESULTS:
      Control rats and rats that received a low dose of MEC (7 microg/infusion) with
      cocaine increased their average hourly intake over 5 days of 6 h per day cocaine
      access. Rats that received a higher dose of MEC (70 microg/infusion) did not
      increase their intake of cocaine during 6 h access but continued to self
      administer cocaine. When MEC was removed, this group showed an escalation in
      cocaine self-administration. MEC did not alter cocaine intake in a group that had
      continuous 1 h access. CONCLUSIONS: Antagonism of nAChRs during the initial
      exposure to extended cocaine self-administration access time prevented escalation
      of, but did not eliminate, drug intake. These findings indicate that MEC
      sensitive nAChRs are critical for determining cocaine intake as a function of
      longer access time.

PMID- 17530476
TI  - Distinct electrophysiological effects of paliperidone and risperidone on the
      firing activity of rat serotonin and norepinephrine neurons.
AB  - RATIONALE: Paliperidone (9-OH-risperidone) is the main metabolite of the atypical
      antipsychotic risperidone. While both drugs are potent dopamine (D)2 antagonists,
      they have quantitative differential affinities for serotonin (5-HT) and
      norepinephrine (NE) receptor binding sites. OBJECTIVES: The present study aimed
      to determine if paliperidone exerts distinct effects on 5-HT and NE neuronal
      activity from those of risperidone. MATERIALS AND METHODS: Risperidone and
      paliperidone were administered to Sprague-Dawley rats. Neuronal activity of 5-HT
      and NE neurons was assessed using in vivo electrophysiology. RESULTS: Acute
      administration of risperidone but not paliperidone inhibited the firing of 5-HT
      neurons, as previously reported. This inhibition was partially antagonized by the
      NE reuptake inhibitor desipramine, by the 5-HT(1A) receptor antagonist WAY
      100635, and completely reversed when both drugs were given consecutively.
      Risperidone inhibited the firing of 5-HT neurons after 2 and 14 days of
      administration, with or without escitalopram. Paliperidone did not alter the
      firing rate of NE neurons by itself, but it reversed the suppression of NE
      neurons induced by escitalopram, as it was previously reported for risperidone.
      CONCLUSION: These results indicate that although risperidone and paliperidone
      share a qualitatively similar receptor binding profile in vitro, they
      differentially alter the firing of 5-HT and NE neurons in vivo. The capacity of
      paliperidone to reverse the selective serotonin reuptake inhibitor (SSRI)-induced
      inhibition of NE neuronal firing, without interfering with the effect of SSRIs of
      5-HT neuronal activity, suggests that paliperidone may be a very effective
      adjunct in SSRI-resistant depression.

PMID- 17530477
TI  - Epidemiological studies on tick-borne diseases of cattle in Central Equatoria
      State, Southern Sudan.
AB  - A herd-based study was carried out in Central Equatoria State, Southern Sudan, to
      study epidemiological aspects of tick-borne diseases. Six herds of cattle
      situated in three different locations were selected and investigated every 3
      months during the year 2005. Blood smears for Giemsa staining and blood spots on
      filter paper for deoxyribonucleic acid extraction were collected from 600
      apparently healthy indigenous cattle. A total of 69 (11.5%) samples showed the
      presence of piroplasms in Giemsa-stained blood smears, and polymerase chain
      reaction increased the detection limit to 297 (49.5%). Using reverse line blot,
      it was possible to detect and differentiate eight different piroplasms namely,
      Theileria parva (71.2%), Theileria mutans (73%), Theileria velifera (45.3%),
      Theileria taurotragi (2.7%), Theileria buffeli (0.5%), Theileria annulata (0.2%),
      Babesia bovis (1.7%), and Babesia bigemina (0.3%). Mixed infections were detected
      in 406 samples (67.7%) accounting for 17 different combinations. High infection
      of Theileria parva was reported among young calves compared to older cattle. The
      highest prevalence of Theileria parva was reported in the rainy season (October).
      The implications of these results on the epidemiology of tick-borne diseases are
      discussed with emphasis on East Coast fever.

PMID- 17530478
TI  - Relative quantification of immune-regulatory genes in two rainbow trout strains,
      Oncorhynchus mykiss, after exposure to Myxobolus cerebralis, the causative agent
      of whirling disease.
AB  - Expression of immune-regulatory genes that code for cyclooxigenase-2 (COX-2),
      transforming growth factor beta (TGF-beta), and two isoforms of interleukin-1beta
      (IL-1beta1 and IL-1beta2) was studied in susceptible and non-susceptible rainbow
      trout strains for 200 days after exposure to Myxobolus cerebralis. Expression of
      COX-2, IL-1beta1, and IL-1beta2 increased 5 min post exposure (p.e.) and was
      always more elevated in the susceptible strain than in the non-susceptible
      strain. In both strains, expression of COX-2 returned to the control level within
      a few hours p.e. Expression of IL-1beta1 and IL-1beta2 showed two elevated waves
      in both strains until 4 days p.e. Expression of TGF-beta in the non-susceptible
      strain was elevated at nearly all sampling points, but was decreased in the
      susceptible strain until up-regulation between 4 and 20 days p.e.; TGF-beta was
      the only gene where the expression in the non-susceptible strain was more
      elevated than in the susceptible strain. Rainbow trout of the non-susceptible
      strain appeared to resist infection by M. cerebralis with only minor
      transcriptional regulation of the genes investigated. Increased transcriptions of
      genes in the susceptible strain may be the result of an inability to antagonize
      the infection.

PMID- 17530479
TI  - Genetic heterogeneity of Fasciola hepatica isolates in the northwest of Spain.
AB  - The liver fluke Fasciola hepatica is a worldwide distributed trematode parasite
      of great veterinary importance. In Spain, the prevalence of the infection is up
      to 56% in sheep. Its control is mainly based on the use of anthelmitics, although
      some resistant populations have been described. Genetic studies of the genus
      Fasciola have been focused on the 28S ribosomal deoxyribonucleic acid (rDNA)
      gene, with no intraspecific variations and a few interspecific nucleotide
      differences. We have designed a specific polymerase chain reaction to amplify and
      sequence a 510-bp-long fragment of the gene to characterize several F. hepatica
      ovine isolates from the northwest of Spain. All the isolates rendered the
      expected results on the agarose gel, while sequencing revealed some differences
      in the 34 site. The anthelmintic-resistant specimens showed the same nucleotide
      differing of the sensitive ones. Comparing to other studies, our results conclude
      that there are some genetic variations in F. hepatica (at the level of the 28S
      rDNA), including heterozygous specimens. In conclusion, a genetic heterogeneity
      has been found in the F. hepatica populations of ovine origin in the northwest of
      Spain, using an assay that could be useful for further epidemiology and
      characterization studies.

PMID- 17530480
TI  - Oligopeptidase B from L. amazonensis: molecular cloning, gene expression analysis
      and molecular model.
AB  - Serine oligopeptidases of trypanosomatids are emerging as important virulence
      factors and therapeutic targets in trypanosome infections. A complete open
      reading frame of oligopeptidase B from Leishmania amazonensis was amplified with
      polymerase chain reaction with gradient annealing temperatures using primers
      designed for the oligopeptidase B gene from L. major. The 2,196-bp fragment coded
      for a protein of 731 amino acids with a predicted molecular mass of 83.49 KDa.
      The encoded protein (La_OpB) shares a 90% identity with oligopeptidases of L.
      major and L. infantum, 84% with L. braziliensis, and approximately 62 identity
      with Trypanosoma peptidases. The oligopeptidase B gene is expressed in all cycle
      stages of L. amazonensis. The three dimensional model of La_OpB was obtained by
      homology modeling based on the structure of prolyl oligopeptidases. We mapped a
      La_OpB model that presents a greater negative charge than prolyl oligopeptidases;
      our results suggest a difference in the S2 subsite when compared to
      oligopeptidases B from Trypanosoma and bacterial oligopeptidases B. The La_OpB
      model serves as a starting point for its exploration as a potential target source
      for a rational chemotherapy.

PMID- 17530482
TI  - Tropisetron, ondansetron, and granisetron for control of chemotherapy-induced
      emesis in Turkish cancer patients: a comparison of efficacy, side-effect profile,
      and cost.
AB  - BACKGROUND: Tropisetron, ondansetron, and granisetron are considered equally
      efficacious, supported by several international studies. However, there are
      interindividual variations in their metabolism that could affect efficacy. The
      clustering of such variations may change from one to another nation. Therefore,
      their equality must be validated in Turkish patients. The aim of this study was
      to compare their efficacies, side-effect profiles, and costs in the prophylaxis
      of emesis induced by moderate to high emetogenic chemotherapies. METHODS: A total
      of 158 patients with a median age of 48 years, 115 (72.8 percent) female and 43
      (27.2 percent) male, were included, respectively. Fifty-one, 61, and 46 patients
      were allocated to tropisetron (5 mg), ondansetron (8 mg), and granisetron (3 mg
      IV) in combination with 8 mg dexamethasone, which were continued 5 mg once a day,
      8 mg b.i.d. and 1 mg b.i.d. PO for 5 days, respectively. RESULTS: The complete
      response (CR) rates in the control of acute emesis were 80.4 percent with
      tropisetron, 72.1 percent with ondansetron, and 71.7 percent granisetron (p =
      0.877). CR rates in delayed emesis (Days 2-5) were 68.6 percent, 68.9 percent,
      and 76.1 percent, respectively (p = 0.527). Rates of freedom from nausea in the
      same period were 37.3 percent, 35.9 percent, and 33.9 percent (p = 0.949). Nausea
      control rates, side-effect profile did not differ. However, headache seemed to be
      encountered higher (45.6 percent) in Turkish patients than others (3.9-9
      percent). Tropisetron is the least expensive one ($95.3 per cycle) according to
      current prices in Turkey. CONCLUSIONS: There were no differences among the 3
      serotonin antagonists with respect to efficacy and frequency of side-effects in
      our patients. Tropisetron is the least expensive at current prices. The choice
      may be based on other parameters, such as ease of administration and patient
      preference.

PMID- 17530483
TI  - Randomized Phase II trial of thalidomide alone versus thalidomide plus interferon
      alpha in patients with refractory multiple myeloma.
AB  - The potential synergistic anti-myeloma effect for thalidomide combining with
      interferon alpha was not yet clear clinically. From March 2001 to January 2004, a
      total of 28 heavily pretreated multiple myleoma (MM) patients were enrolled in
      this open-labeled, randomized Phase II study. Patients with refractory MM were
      randomized to receive either thalidomide alone (200 mg/day up to the maximum dose
      800 mg/day, arm B) or the combination of thalidomide and interferon alpha (3
      MIU/m(2) subcutaneous injection 3 times weekly, arm A). The objective of this
      study was to compare the safety and efficacy of thalidomide alone to combined
      regimen. The patients' characteristics were similar between the 2 arms. However,
      the average treatment duration was significantly longer in the arm B than the arm
      A (236 days versus 101 days, p = 0.029). Serum levels of paraprotein decline >/=
      25 percent were obtained in 6 of 12 patients (50.0 percent) treated with arm B
      and 3 of the 16 patients (18.8 percent) treated with arm A. The estimated time to
      event was 7.9 months (95 percent confidence interval [95%CI], 0.5-15.4) for arm B
      and 1.5 months (95%CI, 0.0-3.4) for arm A (log-rank test, p = 0.0193). The major
      adverse events in both arms consisted of neutropenia, anemia, thrombocytopenia,
      constipation, somnolence, and skin rash. Our study showed that thalidomide alone
      was effective and tolerated in patients with relapsed or refractory MM. The
      thalidomide combined with interferon alpha resulted in a lower frequency of
      paraprotein response, shorter treatment-duration and 25 percent of patients'
      refusing rate. It may be concluded that the combined regimen is not well
      tolerated in our patients and needed to be further evaluated in the future.

PMID- 17530484
TI  - A Phase I dose-finding study using an innovative sequential biweekly schedule of
      irinotecan followed 24 hours later by capecitabine.
AB  - BACKGROUND: Irinotecan and capecitabine have a broad spectrum of activity in
      human malignancy and are synergistic in an animal model when irinotecan precedes
      capecitabine. PATIENTS AND METHODS: A Phase I design of the combination of
      irinotecan IV Day 1 with capecitabine on Days 2-8 every 2 weeks was evaluated in
      27 adult patients with solid tumors. Two sequential schema were used: Arm A fixed
      the dose of irinotecan at 100 mg/m(2) and escalated capecitabine in cohorts, and
      arm B fixed the dose of capecitabine at 750 mg/m(2) PO BID and escalated the
      dosage of irinotecan. RESULTS: Neutropenia was dose limiting with nausea and
      diarrhea as the most common nonhematological toxicities. Significant interpatient
      variation in toxicity occurred despite uniform dosing. No Grade IV toxicities
      were encountered. Grade III toxicity occurred in first cycle in 15 percent (3/20)
      patients in arm A and 29 percent (2/7) of patients in arm B. All toxicities were
      reversible. Repetitive dosing was feasible with prolonged disease stabilization
      in 8 patients. CONCLUSIONS: The suggested Phase II dose of this combination and
      schedule is irinotecan 100 mg/m(2) and capecitabine 1000 mg/m(2) BID. Some
      patients tolerated a capecitabine dose as high as 1250 mg/m(2) BID.

PMID- 17530485
TI  - Expression of glucose transporter-1, hexokinase-II, proliferating cell nuclear
      antigen and survival of patients with pancreatic cancer.
AB  - OBJECTIVES: 18F-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET)
      has been shown to be useful in diagnosis and staging of pancreatic cancer.
      However, the prognostic value of FDG-PET remains controversial. The aim of this
      study was to evaluate relations between the factors suggested to be related to
      the FDG accumulation in tumor tissue, such as glucose transporter-1 (GLUT-1),
      hexokinase type-II (HK-II), proliferating cell nuclear antigen (PCNA), and
      survival of pancreatic cancer patients. METHODS: Histological specimen of
      pancreatic cancer obtained from seventy-four consecutive patients were evaluated
      for the expression of GLUT-1, HK-II, and PCNA by visual analysis of
      immunohistochemical staining of paraffin sections from the tumor specimens using
      anti-GLUT-1, anti-HK-II, and anti-PCNA antibody, respectively. The percentages of
      cells strongly expressing GLUT-1, HK-II and PCNA were scored on a 5-point scale
      (1 = 0-20 percent, 2 = 20-40 percent, 3 = 40-60 percent, 4 = 60-80 percent, 5 =
      80-100 percent). After initial treatment, each patient was followed-up and
      survival time was recorded. Median survival curves of the patients with different
      levels of GLUT-1, HK-II, and PCNA expression were evaluated using the Kaplan
      Meier method. Statistical significance of the differences in survival was
      calculated with the log rank test. RESULTS: Median survival of examined patients
      showed no relation with the levels of GLUT-1 expression, while patients with low
      expression of HK-II (HK-II index < 3) had significantly shorter survival than
      those with higher expression of HK-II (HK-II index >/= 3) (6.5 +/- 4.1 versus
      12.9 +/- 22.4 months, respectively, p < 0.05). Median survival of examined
      patients also showed significant relations with the levels of PCNA expression.
      Patients with low expression of PCNA (PCNA index < 4) had significantly longer
      survival than those with higher expression of PCNA (PCNA index >/= 4) (11.9 +/-
      20.1 versus, 5.8 +/- 10.8 months, respectively, p < 0.01): CONCLUSIONS: Our
      results showed that the expression of GLUT-1 had no prognostic value in the
      examined patients with pancreatic cancer. On the other hand, high levels of HK-II
      expression and low levels of PCNA expression may allow accurate identification of
      the patient with longer survival who may benefit from intensive anticancer
      treatment.

PMID- 17530486
TI  - Time factor in radiotherapy and chemotherapy for limited disease small-cell lung
      cancer.
AB  - The prognostic significance of planned and unplanned gaps in radiotherapy and
      chemotherapy for limited-disease small-cell lung cancer (LD-SCLC) has been
      retrospectively evaluated in a series of 245 patients. All of them had cisplatine
      based chemotherapy and fractionated radiotherapy. There was substantial
      heterogeneity in overall radiation treatment time and dose-intensity of
      chemotherapy attributable mostly to planned and unplanned gaps in therapy.
      Several variables that potentially may influence survival of the patients after
      treatment, including duration of treatment gaps, and dose-intensity of
      chemotherapy and radiotherapy were analyzed using univariate and multivariate Cox
      regression model. The following variables had significant and independent
      negative influence on survival in a multivariate model: performance status ZUBROD
      > 0 (p < 0.0001), metastases to supraclavicular nodes (p = 0.001), dyspnoea
      according to Borg scale > 2 (p = 0.004) and the average dose intensity of
      radiotherapy < 80 percent (p = 0.02). An independent association between total
      dose and survival also has been found. The dose-intensity of chemotherapy did not
      appear to significantly influence survival. While due to the retrospective
      character of the present research, this conclusion must be regarded as hypothesis
      generating only, we assume that within the range of doses and dose-intensitites
      used in the present group the preventable gaps in radiotherapy and undue
      reduction of total radiation dose should be promptly avoided, while gaps in
      chemotherapy can be deemed acceptable if crucially demanded by the tolerance of
      treatment.

PMID- 17530487
TI  - Tensiometric profiles and their modulation by cholesterol: implications in
      cervical cancer.
AB  - Langmuir monolayers offer a convenient model for understanding the behavior of
      many natural systems like biological membranes. This technique was used to
      characterize the role of cholesterol, lipophilic, and lipophobic components of
      tissues in cervical cancer by evaluating their tensiometric profiles. Monolayers
      were formed on the surface of deionized water by spreading tissue components
      corresponding to 1 mg of the tissue for studying their surface pressure-area
      isotherms at body temperature. The cholesterol content of cancerous human
      cervical tissues was higher than that of the normal human cervical tissues. The
      addition of 3 mug cholesterol/mg tissue to the normal organic phase changed its
      tensiometric profile to that of the cancerous profile. Statistically significant
      tensiometric parameters showed that cholesterol acts as a rigidifier in the
      cervical tissues and has a remarkable role in shifting the normal cervical
      lipophilic surface activity towards that of the cancerous lipophilic monolayer.
      Several mixtures of the lipophilic-lipophobic components of both cancerous as
      well as normal cervical tissues also were characterized to reveal the relative
      contribution of these phases in the cervical cancer tensiometric profiles. Though
      the actual ratio of aqueous and organic phases in the normal tissue was 97:3 by
      weight, the tissue homogenate behavior was similar to that of a 50:50 mixture by
      weight, indicating the nonadditivity of the lipophilic-lipophobic components. The
      addition of cholesterol to a 97: 3 by weight aqueous: organic mixture of normal
      cervical tissue also revealed the rigidifying role of cholesterol. Unlike in
      normal tissue homogenates, the cancerous tissue homogenate tensiometric profile
      had more contribution from its aqueous phase components and an additive
      interaction between the lipophilic and lipophobic components was observed in the
      tissue homogenate. Thus, distinct differences in the interactions between
      lipophilic and lipophobic components were observed in cancerous and normal
      states. The Langmuir monolayer technique was sensitive to detect such changes in
      the form of altered tensiometric profiles. Therapeutic strategies may be designed
      to modulate these tensiometric profiles to our benefit.

PMID- 17530488
TI  - Evaluation of the combination of docetaxel/carboplatin in patients with
      metastatic or recurrent squamous cell carcinoma of the head and neck (SCCHN): a
      Southwest Oncology Group Phase II study.
AB  - Carboplatin/docetaxel chemotherapy was evaluated in advanced squamous cell
      carcinoma of the head and neck (SCCHN). Eligibility included patients with
      recurrent, persistent, or metastatic SCCHN with Zubrod performance status 0-2.
      Docetaxel 65 mg/m(2) and carboplatin (AUC of 6) were given IV in a 21-day cycle
      to 68 patients. Response probability was 25 percent (95%CI: 15-38). The major
      toxicity observed was neutropenia, with 36 patients (61 percent) experiencing
      Grade 3 or worse. Median progression-free survival was 3.8 months (95%CI, 3.1
      4.8) Median overall survival was 7.4 months (95%CI, 6.2-8.9). The results of this
      study suggest this regimen is active for outpatient treatment of recurrent SCCHN
      patients with good performance status.

PMID- 17530489
TI  - Carcinogenic food contaminants.
AB  - A large number of scientific studies and reviews have addressed the potential for
      dietary components to influence the risk of developing cancer. One topic of
      particular interest has been the impact of food contaminants. Two complementary
      programs, among others, have reviewed and synthesized information on the
      carcinogenic potential of food contaminants and judged the degree of evidence
      linking different food contaminants to the risk of cancer in humans. These
      programs, the International Agency for Research on Cancer's IARC Monographs on
      the Evaluation of Carcinogenic Risks to Humans and the US National Toxicology
      Program's Report of Carcinogens have reviewed hundreds of chemicals, mixtures,
      and natural products and then graded the cancer risk posed to humans.
      Contaminants with the highest level of evidence include aflatoxin, alcoholic
      beverages, 2,3,7,8-tetracholordibenzo-p-dioxin. Agents with a moderate level of
      evidence include acetaldehyde, polycyclic aromatic hydrocarbons, some
      nitrosamines, and yerba mate. Agents with a low level of evidence include bracken
      fern, fumonsin B(1), ochratoxin, and others. This review presents a summary of
      the evidence for the carcinogenicity of these and other agents and the ranks
      provided by two important assessment programs.

PMID- 17530490
TI  - Telomere biology of pediatric cancer.
AB  - One of the hallmarks of cancer is limitless proliferative capacity, which is
      tightly associated with the ability to maintain telomeres. Over the last decade,
      the telomere biology of pediatric cancers has begun to be elucidated. Most
      pediatric leukemias and embryonal solid tumors activate the enzyme telomerase, a
      specialized reverse transcriptase that adds nucleotide repeats to telomeres. In
      general, high levels of tumor telomerase expression are associated with
      unfavorable outcome, although results vary according to tumor type. Some
      pediatric tumors, including osteosarcoma and glioblastoma multiforme, lack
      telomerase activity and maintain telomeres via a recombination-based mechanism
      called ALT (alternative lengthening of telomeres). Telomerase is a highly
      attractive therapeutic target for pediatric cancer because the enzyme plays a key
      role in conferring cellular immortality, is present in most tumors, and is
      relatively specific for cancer cells. Telomerase inhibitors have been evaluated
      in preclinical models of adult cancers, but few studies have been conducted on
      pediatric cancers. Further research is required to define how telomere biology
      can be used to clinical advantage in malignancies of childhood.

PMID- 17530491
TI  - A traditional jewish approach to risky medical treatment.
AB  - The area of oncology in particular deals with patient treatments that entail
      significant risk. The approach of Jewish law is valuable in formulating a generic
      approach to the area of risky medical treatments and is beneficial in
      understanding the choices that Jewish patients might make regarding their care.

PMID- 17530492
TI  - Memory bias for threat in generalized anxiety disorder: the potential importance
      of stimulus relevance.
AB  - Information processing models propose that anxious individuals are characterized
      by memory biases for mood-congruent threat information. However, evidence for
      memory biases in generalized anxiety disorder (GAD) has been mixed at best. Given
      the heterogeneity of concerns in GAD, previous use of nomothetic stimulus sets
      may have precluded detection of memory biases. Therefore, in order to guarantee
      the relevance of the stimuli used, in the current study individuals with GAD each
      individually selected words that were of personal relevance to them. Using these
      idiographically selected words with 23 individuals with DSM-IV GAD and 23 non
      anxious controls (NACs), results showed an implicit memory bias for threat words
      in individuals with GAD compared with NACs. Furthermore, there was additional
      evidence that individuals with GAD may also be characterized by explicit memory
      bias for threat words. The magnitude of group differences for explicit recall of
      threat words was similar to those previously observed in panic disorder.
      Limitations and future directions are discussed.

PMID- 17530493
TI  - Prevention of pathological gambling: a randomized controlled trial.
AB  - Although the gambling industry is expanding rapidly throughout North America and
      around the world, there are only a few empirically evaluated programs aimed at
      the prevention of pathological gambling (PG). The purpose of this study was to
      measure the effectiveness of a new prevention program aimed at PG. The Stop &
      Think! program was designed to teach at-risk video lottery terminal (VLT)
      gamblers cognitive restructuring and problem-solving skills that may help to
      prevent the development of PG. These skills were taught through a variety of
      methods - including an automated educational presentation, video and text
      vignettes, audio training tapes, and skill rehearsal. The program was evaluated
      using a randomized, 2-group experimental design with a wait-list control group
      and pre-, post-, and follow-up measures. Results indicated that, compared with
      the control group, the experimental group was less at risk for developing a
      gambling problem after the program. The experimental group endorsed fewer
      gambling-related cognitive distortions, engaged in less VLT gambling, and had
      lower scores on a measure of PG. The results of this study provide the basis for
      the implementation of the Stop & Think! program in the province of Prince Edward
      Island, Canada, and perhaps other jurisdictions too.

PMID- 17530494
TI  - Promoting adaptive foot movements and reducing hand mouthing and eye poking in a
      boy with multiple disabilities through microswitch technology.
AB  - This study assessed the viability of a microswitch cluster (i.e. a combination of
      microswitches) plus contingent stimulation for promoting adaptive responding and
      reducing aberrant behavior in a boy with profound multiple disabilities. The boy
      was initially taught an adaptive foot-movement response that activated a motion
      microswitch and produced preferred stimuli. Subsequently, his foot response led
      to preferred stimuli only if it occurred in the absence of aberrant behavior
      (i.e. hand mouthing and eye poking which were detected through optic
      microswitches). Moreover, full access to the stimuli required that the boy
      refrain from aberrant behavior during their presentation as well. The study also
      included a 3-month post-intervention check and a social validation assessment.
      Data showed that the boy (i) increased his adaptive responding, (ii) learned to
      perform this responding largely free from aberrant behavior and refrained from
      that behavior for most of the session time, and (iii) maintained this performance
      at the post-intervention check. The social validation ratings of 40 teachers and
      teacher assistants significantly favored the last intervention period (in which
      aberrant behavior was reduced) over the initial period.

PMID- 17530495
TI  - Emotional-vulnerability and mindfulness: a preliminary test of associations among
      negative affectivity, anxiety sensitivity, and mindfulness skills.
AB  - This study evaluated associations between general (negative affectivity) and
      specific (anxiety sensitivity) factors that may relate to the mindfulness skill
      domains assessed by the Kentucky Inventory of Mindfulness Skills. Participants
      were 154 young adults (88 females; M(age) = 22.4 years, SD = 7.9) recruited from
      the community. Partially consistent with predictions, higher levels of negative
      affectivity were significantly associated with lower levels of Awareness,
      Acceptance, and Describe mindfulness skills, and higher levels of anxiety
      sensitivity were significantly associated with lower levels of Awareness and
      Acceptance mindfulness skills. Additionally, negative affectivity and anxiety
      sensitivity each demonstrated unique relations to participants' ability to
      experience the present state without evaluating or judging its content (Accept
      factor), after accounting for their shared variance, but only anxiety sensitivity
      demonstrated a unique association to the Act with Awareness factor independent of
      variance explained by negative affectivity. Findings are discussed in relation to
      theory and research on mindfulness processes.

PMID- 17530496
TI  - Impact of experimentally induced positive and anxious mood on alcohol expectancy
      strength in internally motivated drinkers.
AB  - The effects of musically-induced positive and anxious mood on explicit alcohol
      related cognitions (alcohol expectancy strength) in 47 undergraduate students who
      consume alcohol either to enhance positive mood states (for enhancement motives)
      or to cope with anxiety (for anxiety-related coping motives) were investigated.
      Pre- and post-mood induction, participants completed the emotional reward and
      emotional relief subscales of the Alcohol Craving Questionnaire - Now. The
      hypothesis that anxiety-related coping motivated drinkers in the anxious mood
      condition (but not those in the positive mood condition) would exhibit increases
      in strength of explicit emotional relief alcohol expectancies after the mood
      induction was supported. An additional, unanticipated finding was that
      enhancement-motivated drinkers in the anxious condition also showed significant
      increases in strength of explicit emotional relief (but not emotional reward)
      alcohol expectancies. The hypothesis that enhancement-motivated (but not anxiety
      related coping motivated) participants would exhibit increases in explicit
      emotional reward expectancies following exposure to the positive mood induction
      procedure was not supported. Taken together with past research findings, the
      current results highlight the importance of distinguishing between subtypes of
      negative affect (i.e., anxious and depressed affect) in exploring the affective
      antecedents of explicit alcohol outcome expectancies.

PMID- 17530497
TI  - Predictors of post-event rumination related to social anxiety.
AB  - Post-event processing is the cognitive rumination that follows social events in
      cognitive models of social anxiety. The aim of this study was to examine factors
      that may predict the extent to which individuals engage in post-event processing.
      Anxious rumination, social anxiety, anxiety sensitivity and post-event processing
      related to a recent anxiety-provoking social event were assessed in a college
      student sample (n = 439). Social anxiety and anxious rumination, but not anxiety
      sensitivity, significantly predicted the extent to which the participants engaged
      in post-event processing related to an anxiety-provoking social event. Factors
      that appear to impact on the post-event period include the nature of the social
      situation and the ethnicity of the participant. It appears that both general
      rumination over anxious symptoms, and specific rumination related to social
      events are relevant for cognitive models of social anxiety.

PMID- 17530501
TI  - Don't diagnose mild COPD without confirming airway obstruction after an inhaled
      bronchodilator.

PMID- 17530502
TI  - Evaluation of small sample cDNA amplification for microdissected airway
      expression profiling in COPD.
AB  - Small airway obstruction and emphysematous destruction account for the airflow
      limitation that defines chronic obstructive pulmonary disease (COPD). While laser
      capture microdissection (LCM) allows gene expression studies in small airways
      separately from the surrounding parenchyma, tissue size limits the number of
      genes examined. The present study evaluates the Clontech SMART amplification to
      test the hypothesis that this amplification provides RNA in sufficient quantity
      and quality to evaluate large numbers of genes in airways < 2 mm diameter
      obtained by LCM. Commercial reference RNA was amplified 200-fold and the
      expression levels of 51 genes relative to the unamplified RNA had a correlation
      coefficient of 0.84. For two pairs of RNA preparations (commercial placenta
      versus commercial lung; lung sections prepared for LCM from GOLD 0 (at risk for
      COPD) versus GOLD 2 (moderate disease) patients linear regression of Delta Ct's
      (delta cycle thresholds) of unamplified versus amplified RNA gave correlation
      coefficients of R = 0.95. In RNA from microdissected small airways, expression
      patterns in all GOLD classes of COPD severity were very similar between
      unamplified and amplified RNA. We conclude that SMART amplification provides cDNA
      sufficient for studying large numbers of genes even in laser-captured small
      airways and this cDNA maintains the relative expression found in corresponding
      unamplified RNAs.

PMID- 17530503
TI  - Activity monitoring and energy expenditure in COPD patients: a validation study.
AB  - There is increasing interest in the objective measurement of physical activity in
      chronic obstructive pulmonary disease (COPD) patients due to the close
      relationship between physical activity level, health, disability and mortality.
      We aimed to (a) determine the validity and reproducibility of an activity monitor
      that integrates accelerometry with multiple physiologic sensors in the
      determination of energy expenditure in COPD subjects and (b) to document the
      independent contribution of the additional physiologic sensors to accelerometry
      measures in improving true energy expenditure determination. Eight subjects (4
      male, FEV(1) 56.4 +/- 14.1%, RV 145.0 +/- 75.7%) performed 2 separate 6-minute
      walk and 2 incremental shuttle walk exercise tests. Energy expenditure was
      calculated during each exercise test using the physiologic activity monitor and
      compared to a validated exhaled breath metabolic system. Test-retest
      reproducibility of physiologic activity monitor during the walking tests was
      comparable to an exhaled breath metabolic system. Physiologic sensor data
      significantly improved the explained variance in energy expenditure determination
      (r(2)=0.88) compared to accelerometry data alone (r(2)=0.68). This physiologic
      activity monitor provides a valid and reproducible estimate of energy expenditure
      during slow to moderate paced walking in a laboratory setting and represents an
      objective method to assess activity in COPD subjects.

PMID- 17530504
TI  - Impact of bronchodilator use on the prevalence of COPD in population-based
      samples.
AB  - The aim of this study was to describe the impact of using bronchodilators on the
      prevalence of Chronic Obstructive Pulmonary Disease in a population-based survey
      (Platino study). A cluster sampling of subjects 40 years of age or older,
      representative of the metropolitan areas of 5 Latin American cities (Sao Paulo,
      Mexico, Montevideo, Santiago and Caracas) was chosen. Spirometry according to ATS
      standards was done before and after inhalation of 200 micrograms of salbutamol in
      5183 subjects. Prevalences of airflow obstruction were estimated using different
      criteria, in tests done before and after bronchodilator use, and with reference
      values for pre- or post-bronchodilator use. Bronchodilator testing reduced the
      overall prevalence of FEV(1)/FVC% < 0.70 from 21.7% to 14% (35%). In the group
      with FEV(1)/FVC < 0.70 after bronchodilator use, 21% were asymptomatic from the
      respiratory point of view, and lacked significant adverse exposures. Subjects
      below the 5th percentile for FEV(1)/FVC and FEV(1)/FEV(6) were fewer than those
      with FEV(1)/FVC < 0.70, especially among the elderly. More subjects are below the
      5th percentile of FEV(1)/FVC and FEV(1)/FEV(6) using reference values for tests
      after bronchodilator use than using the reference values determined without
      bronchodilator testing. Testing after bronchodilator use reduces the prevalence
      of airflow obstruction from 32 to 39% depending on the definition used. In
      addition, the subjects who were still obstructed after bronchodilator use were
      the ones who showed more respiratory symptoms and exposure to tobacco and other
      smokes and dusts, than subjects with reversible obstruction, suggesting an
      increased specificity for COPD.

PMID- 17530505
TI  - Insulin resistance and inflammation - A further systemic complication of COPD.
AB  - Chronic obstructive pulmonary disease (COPD) is associated with a continuous
      systemic inflammatory response. Furthermore, COPD is associated with an excess
      risk for cardiovascular disease and type II diabetes. Systemic inflammation in
      other populations is a factor in atherogenesis and has been associated with
      insulin resistance. We assessed the association between systemic inflammation and
      insulin resistance in non-hypoxaemic patients with COPD. Fasting plasma glucose,
      insulin and inflammatory mediators were measured in 56 patients and 29 healthy
      subjects. Body mass index (BMI) and height squared fat- and fat-free-mass index
      were similar between subject groups. Using homeostatic modelling techniques, mean
      (SD) insulin resistance was greater in the patients, 1.68 (2.58) and 1.13 (2.02)
      in healthy subjects, p=0.032. Fasting plasma insulin was increased in patients
      while glucose was similar to that in healthy subjects. Patients had increased
      circulating inflammatory mediators. Insulin resistance was related to interleukin
      6 (IL-6), r=0.276, p=0.039, and tumour necrosis factor alpha soluble receptor I,
      r=0.351, p=0.008. Both IL-6 and BMI were predictive variables of insulin
      resistance r(2)=0.288, p<0.05. We demonstrated greater insulin resistance in non
      hypoxaemic patients with COPD compared with healthy subjects, which was related
      to systemic inflammation. This relationship may indicate a contributory factor in
      the excess risk of cardiovascular disease and type II diabetes in COPD.

PMID- 17530506
TI  - Survival among COPD patients using fluticasone/salmeterol in combination versus
      other inhaled steroids and bronchodilators alone.
AB  - Recent retrospective studies have suggested that use of inhaled corticosteroids
      (ICS) may improve survival in chronic obstructive pulmonary disease (COPD),
      particularly when combined with a long-acting beta-agonist (LABA). However, the
      study methodologies have been questioned, and no study has examined the survival
      effect of the newer combination ICS/LABA inhalers. The goal of this project was
      to further examine the relationship between ICS treatment, with or without LABA,
      and survival in COPD. COPD patients were identified from the administrative
      databases of four different integrated health care delivery systems. All patients
      who were diagnosed with COPD between September 1, 2000 and August 31, 2001 and
      who had at least 3 months treatment with either a combined fluticasone/salmeterol
      inhaler (FSI, N=866), any ICS used with a LABA (ICS/LABA, N=525), ICS alone
      (N=742), LABA alone (N=531), or a short-acting bronchodilator alone (SABD,
      N=1832), were included. Analyses were conducted using three different analysis
      approaches that adjust for various biases that may affect the results. In the
      basic Cox proportional hazards models, use of FSI, ICS/LABA, ICS alone, and LABA
      alone had significant survival benefits as compared to SABD, after adjustment for
      differences in age, gender, comorbidities, asthma status, and disease severity
      (HRs 0.61 [0.45-0.83], 0.59 [0.46-0.77], 0.76 [0.61-0.95], 0.75 [0.57-0.98],
      respectively). Propensity score matching to reduce the clinical differences
      between the treatment groups versus the SABD reference group found very similar
      results. Nested case-control analyses, which are based on survival status instead
      of treatment, continued to show a significant survival benefit for FSI, ICS/LABA,
      and ICS alone. Treatment with FSI or another ICS with or without LABA is
      associated with improved survival in COPD. The treatment benefit is reproducible
      and is robust to application of a number of different analysis techniques
      designed to adjust for differences in confounding variables and for bias by
      indication.

PMID- 17530507
TI  - Impact of regular inhaled corticosteroid use on chronic obstructive pulmonary
      disease outcomes.
AB  - Inhaled corticosteroids are often used to manage chronic obstructive pulmonary
      disease, although the evidence regarding their long-term efficacy in preventing
      or reducing adverse health outcomes is not definitive. This retrospective cohort
      study analyzed whether regular inhaled corticosteroid use is associated with
      reduced health care utilization and all-cause mortality related to chronic
      obstructive pulmonary disease. Subjects were 2,902 health maintenance
      organization members aged 50 and over who met criteria for chronic obstructive
      pulmonary disease. The study used a composite endpoint of time to (1) death or
      (2) hospitalization or emergency room care related to chronic obstructive
      pulmonary disease, whichever occurred first, during a 4-year follow-up. Among the
      42% of chronic obstructive pulmonary disease patients with an indication of co
      morbid asthma, inhaled corticosteroid use was associated with significantly
      reduced risk for both all-cause mortality and the composite outcome. The
      reduction in risk was greatest in never- and ex-smokers. Among chronic
      obstructive pulmonary disease patients with no indication of asthma, inhaled
      corticosteroid use was associated with reduced risk only in never smokers. These
      findings generally persisted in separate analyses stratified by asthma status and
      in sensitivity analyses using four alternative definitions of regular medication
      use, with comparable results when regular medication use was treated as a fixed
      covariate defined at the start of follow-up. We conclude that use of inhaled
      corticosteroids was associated with reduced risk of chronic obstructive pulmonary
      disease exacerbations and all-cause mortality. This benefit was most pronounced
      among never-smokers and in those with evidence of co-morbid asthma.

PMID- 17530508
TI  - Imaging in chronic obstructive pulmonary disease.
AB  - Chronic obstructive pulmonary disease (COPD) is divided into pulmonary emphysema
      and chronic bronchitis (CB). Emphysema is defined patho-anatomically as
      "permanent enlargement of airspaces distal to the terminal bronchiole,
      accompanied by the destruction of their walls, and without obvious fibrosis" (1).
      These lesions are readily identified and quantitated using computed tomography
      (CT), whereas the accompanying hyperinflation is best detected on plain chest X
      ray, especially in advanced disease. The diagnosis of CB is clinical and relies
      on the presence of productive cough for 3 months in 2 or more successive years.
      The pathological changes of mucosal inflammation and bronchial wall thickening
      have been more difficult to identify with available imaging techniques. However,
      recent studies using Multi-detector row CT (MDCT) reported more reproducible
      assessment of air wall thickening.

PMID- 17530509
TI  - Nasal and sinus inflammation in chronic obstructive pulmonary disease.
AB  - Epidemiologic studies suggest that as many as 75% of patients with COPD have
      concomitant nasal symptoms and more than 1/3 of patients with sinusitis also have
      lower airway symptoms of asthma or COPD. Because the inflammatory response of the
      upper and lower airways are similar, and both sites have a similar exposure to
      allergens and irritants, it is not surprising that rhinitis or sinusitis would
      coexist with COPD. Possible mechanisms of combined upper and lower airway
      dysfunction include the so-called nasal-bronchial reflex, inflammation caused by
      smoking, mouth breathing caused by nasal obstruction, and pulmonary aspiration of
      nasal contents. Patients with chronic sinusitis commonly have nonspecific
      bronchial hyperresponsiveness, suggesting a neural reflex. Postnasal drainage of
      nasal inflammatory mediators during sleep also may increase lower airway
      responsiveness. Therapy of nasal and sinus disease is associated with improved
      pulmonary function in patients with COPD.

PMID- 17530511
TI  - Maturation of the auditory system: 1. Transient otoacoustic emissions as an index
      of inner ear maturation.
AB  - The transiently evoked otoacoustic emission amplitude of 42 preterm babies (84
      ears; post-conceptional age [PCA] 30-36 weeks) was compared with the TEOAE
      amplitude of 39 full-term babies (78 ears; PCA 37-45 weeks) in order to trace the
      inner ear maturation characteristics. An ILO-92 otoacoustic emission recording
      system was used with linear clicks of 70 dB peak equivalent SPL. The results
      obtained indicated: (1) There was no statistically significant difference between
      preterm and full-term ears; (2) There was no significant difference between males
      and females; (3) There was a significant difference between left and right ear
      TEOAE amplitude; (4) The interaction of ear with age in relation to TEOAE
      amplitude was statistically significant; (5) Noise and stimulus parameters did
      not reveal any significant differences between right and left ears; (6) A
      positive correlation existed between birthweight and TEOAE amplitude; and (7) A
      negative correlation existed between aminoglycoside treatment and TEOAE
      amplitude. The results indicate subtle changes in TEOAE amplitude over time,
      showing a natural development of the inner ear function during the process of
      maturation.

PMID- 17530512
TI  - Maturation of the auditory system: 2. Transient otoacoustic emission suppression
      as an index of the medial olivocochlear bundle maturation.
AB  - Contralateral suppression of transient otoacoustic emissions in 42 premature
      babies (84 ears; post-conceptional age [PCA] 30-36 weeks) was compared to that of
      39 full-term babies (78 ears; PCA: 37-45 weeks). Eighteen healthy adults and ten
      young children (5-14 years old) were studied as controls. Risk factors for
      hearing loss were registered in both preterm and full-term groups. An ILO-92
      otoacoustic emission recording system was used to deliver linear clicks to the
      ear examined and broadband noise to the contralateral ear in an alternating on
      and off mode. Suppression in full-term babies was statistically higher than in
      preterms, whereas no differences existed between children and adults and children
      and full-terms. Peripheral auditory lateralization was evident in adults but was
      observed only as a trend in newborns. Only prematurity at the time of examination
      and aminoglycoside treatment for more than seven days had a negative impact on
      suppression. The results support the conclusion that maturation of the efferent
      system takes place from 30 to 45 weeks PCA. The exact age at which this
      maturation is accomplished has not yet been clearly determined.

PMID- 17530513
TI  - Aided auditory steady-state responses in infants.
AB  - Infants with hearing loss routinely receive hearing aids several months before
      reliable behavioral responses to amplified sound can be observed. This
      necessitates objective measures to validate hearing-aid fittings. A single report
      has demonstrated the use of ASSRs to determine aided thresholds in children but
      data in young infants is still lacking. The current study explored aided ASSR
      compared to unaided ASSR thresholds and subsequent behavioral thresholds in a
      group of six young infants with hearing loss who received hearing aids between
      three and six months of age. Aided ASSR thresholds were obtained in 83% of
      frequencies where aided behavioral thresholds were obtained, with a mean
      threshold difference of 13+/-13 dB. The aided ASSR-based threshold estimates were
      within 15 dB of behavioral thresholds in 63% of cases, indicating a moderate
      correlation (r = 0.55). Comparing aided and unaided ASSR measurements revealed an
      average functional gain of 36+/-15 dB. These results indicate that ASSRs can
      provide the first evidence of robust hearing aid benefit in young infants several
      months before behavioral responses are observed.

PMID- 17530514
TI  - Using transposition to improve consonant discrimination and detection for
      listeners with severe high-frequency hearing loss.
AB  - Transposition of high-frequency information to lower frequencies may help people
      with high-frequency hearing loss associated with a 'dead region' (DR) to detect
      and identify certain consonants, such as 's'. Conventional high-frequency
      amplification is often not beneficial in such cases. We designed and evaluated a
      new transposition algorithm which was adapted to each subject's high-frequency
      DR. Frequency components from well within the DR were transposed to just within
      the DR without applying frequency compression. Low-frequency components were
      amplified, but unaffected by transposition. Transposition only occurred if there
      was significant high-frequency energy, preventing high-frequency background noise
      of moderate level from being transposed. Consonant discrimination was tested
      using vowel-consonant-vowel (VCV) stimuli, and the detection of word-final 's'
      and 'z' was assessed using word pairs. Seven subjects with high-frequency DRs
      were tested in quiet using a transposed and a control condition. Following
      transposition, two subjects improved significantly and none performed
      significantly worse on the VCV-test overall. The perception of affricates was
      consistently improved. Averaged across subjects, the detection of word-final 's'
      and 'z' was significantly improved, with five subjects improving significantly
      individually.

PMID- 17530515
TI  - Binaural interactions of electrically and acoustically evoked responses recorded
      from the inferior colliculus of guinea pigs.
AB  - Binaural interactions within the inferior colliculus (IC) elicited by electric
      and acoustic stimuli were investigated in this study. Using a guinea pig model,
      binaural acoustic stimuli were presented with different time delays, as were
      combinations of binaural electric and acoustic stimuli. Averaged evoked
      potentials were measured using electrodes inserted into the central nucleus of
      the IC to obtain the binaural interaction component (BIC), computed by
      subtracting the sum of the two monaural responses from the binaural response. The
      BICs to acoustic-acoustic stimulation and electric-acoustic stimulation were
      found to be similar. The BIC amplitude increased with stimulus intensity, but the
      shapes of the delay functions were similar across the levels tested. The gross
      potential data are thus consistent with the thesis that the central auditory
      system processes binaural electric and acoustic stimuli in a similar manner.
      These results suggest that the binaural auditory system can process combinations
      of electric and acoustic stimulation presented across ears and that evoked gross
      potentials may be used to measure such interaction.

PMID- 17530516
TI  - A novel service delivery model for infant hearing screening in developing
      countries.
AB  - Newborn hearing screening is the procedure of choice for ensuring optimal
      outcomes for infants with hearing loss, whether in a developed or developing
      country. Unfortunately, apart from a small number of recent exceptions, newborn
      hearing screening has been a practice reserved for the developed world. Despite
      the prevailing challenges towards implementing hearing screening in developing
      countries, there are existing structures in these countries that need to be
      investigated as possible platforms from which programs can be actualized.
      Immunization clinics, constituting part of a primary healthcare approach
      characteristic of developing countries, offer one such a platform. A novel
      service delivery model, based on initial results from a pilot study, was
      developed for infant hearing screening at immunization clinics in South Africa as
      an integrated part of primary, secondary, and tertiary levels of healthcare. This
      type of model is a first step toward ensuring that infants with hearing loss in
      developing communities are afforded opportunities for optimal development and
      societal integration through accountable and contextually relevant early hearing
      detection and intervention services.

PMID- 17530517
TI  - The role of hope in adjustment to acquired hearing loss.
AB  - This study investigated the relationship between individual and disability
      characteristics and adjustment to acquired hearing loss, and the role hope has in
      that relationship. A sample of 114 adults with sensorineural hearing loss who had
      accessed hearing therapy services participated in the study. The mean age of the
      participants was 67 years. A survey of individual and disability characteristics,
      hope and adjustment was conducted. Multiple regression analyses were applied to
      examine possible moderating and mediating models. The results indicate that the
      degree of loss was the only statistically significant individual and disability
      characteristic related to adjustment. The trait of hope was found to serve as a
      mechanism by which the degree of loss affects adjustment. Hearing loss affects
      hope which in turn affects adjustment. Hope was found to account for 45% of the
      relationship between the degree of loss and adjustment. Additionally, the study
      found that self-efficacy and personal meaning may influence hope and despair
      dimensions in different ways. Discussion centres on the implication of these
      findings for intervention strategies used in rehabilitation programmes for those
      with a significant hearing loss.

PMID- 17530518
TI  - Re: hearing loss in patients with enlarged vestibular aqueduct: air-bone gap and
      audiological Bing test.

PMID- 17530519
TI  - Asthma treatment protocols in the emergency department: are they effective?
AB  - Management of asthma in emergency departments (ED) has been well documented to be
      deficient over many years, despite national and international guidelines. This
      review summarizes the effect of ED protocols aimed at improving the assessment
      and treatment of asthma in the ED. We performed a PubMed search of the English
      literature for ED asthma protocols published from 1986 to 2006 and identified 11
      studies. Protocols were effective in improving at least some areas of management,
      including use of appropriate patient assessment, drug therapy per national
      guidelines, and patient education. A small number of protocols with the specific
      aims of reducing the length of stay in the ED as well as rates of hospital
      admission and return visits were effective. Persistent education of ED staff
      regarding protocols based on current management guidelines and adoption of easy
      to-use forms can facilitate improved care of patients with asthma in the ED.

PMID- 17530520
TI  - Impact of asthma and air pollution on school attendance of primary school
      children: are they at increased risk of school absenteeism?
AB  - AIM: The aim of this study was to determine the impact of asthma and air
      pollution on school attendance of primary school children 6 to 12 years of age in
      Qatar. STUDY DESIGN: This was a cross-sectional population-based study. SUBJECTS:
      The total 31,400 Qatari school children at the primary school (16,130 boys and
      15,270 girls) 6 to 12 of age were studied to investigate school absenteeism
      caused by asthma and wheezing during the academic year October 2003 to July 2004.
      METHODS: We have used the School Health Registry for obtaining the student
      information and school absenteeism due to asthma and wheezing. Again we had
      double confirmation on the data obtained on asthmatic children by using the
      modified version of the International Study of Asthma and Allergies in Childhood
      [ISAAC] questionnaire. RESULTS: A total of 3,270 (10.4%) pupils were diagnosed as
      having asthma and wheezing. Overall 2,516 (8.02%) pupils were absent from the
      school for at least one day during the year. There was a statistically
      significant difference between asthmatic and wheezing students in number of days
      absent from the school (p < 0.0001). Most absenteeism occurred during spring for
      both boys (45%) and girls (47%), followed by autumn for boys (33%) and girls
      (36%). The measured pollutants reached a peak during the spring season and then
      in autumn of the studied academic year. CONCLUSION: Children with known asthma
      miss more days of school than those who do not have asthma. This study finding
      shows that air pollution has an impact on asthma, which results in significant
      school absenteeism.

PMID- 17530521
TI  - Tracheopathia osteoplastica misdiagnosed as asthma.
AB  - Tracheopathia osteoplastica (TPO) is a rare disorder characterized by
      cartilaginous or bony mucosal nodules in the tracheobronchial tree. Due to most
      patients being asymptomatic, the majority are diagnosed post-mortem. If symptoms
      are present, they typically include chronic cough, dyspnea, hemoptysis,
      hoarseness, and wheezing, with some of these symptoms overlapping with asthma.
      This case report describes an adult female with chronic cough who was diagnosed
      with asthma that was refractory to therapy for 8 years. Computed tomography (CT)
      of the chest revealed several soft tissue masses in the trachea with bronchoscopy
      revealing TPO in the upper portion of the trachea. She was diagnosed with TPO and
      started on airway clearance and a nasal corticosteroid spray with resolution of
      the cough at follow-up 3 months later.

PMID- 17530522
TI  - Season of birth and risk of atopic disease among children and adolescents.
AB  - BACKGROUND: Season of birth (SOB) has been regarded as a risk factor for atopy.
      The aim of this study was to explore the relationship between season of birth
      (SOB) and later development of atopic disease in children and adolescents.
      METHODS: A total of 1,007 randomly selected subjects, 7 to 17 years of age, who
      were living in urban Copenhagen, Denmark were studied. All participants were
      interviewed about respiratory symptoms and possible risk factors for atopic
      disease. Skin test reactivity, serum total immunoglobulin E (IgE), and airway
      responsiveness were measured using standard techniques. RESULTS: The overall risk
      of atopy, as judged by skin test reactivity and serum total IgE, was the same
      regardless of SOB. On the contrary, asthma was more common in subjects born in
      the autumn compared with subjects born during the remaining part of the year
      (12.4% vs. 5.6%), OR = 2.40, 95% CI (1.56-3.94), p < 0.001. This was observed
      both for atopic asthma OR = 2.41, 95% CI (1.25-4.64), p = 0.007, non-atopic
      asthma, OR = 2.35, 95% CI (1.14-4.83), p = 0.02, and house dust mite (HDM)
      sensitive airway hyperresponsiveness, OR = 3.00, 95% CI (1.44-6.24), p = 0.002.
      Rhinitis and pollen allergy were not significantly related to SOB. CONCLUSIONS:
      Atopy itself is independent of season of birth, whereas asthma is more prevalent
      among subjects born during the autumn. Regarding asthma, these results suggest
      that the first months of life enclose a period of particular vulnerability
      towards environmental risk factors, especially exposure to aeroallergens like
      HDM.

PMID- 17530523
TI  - Asthma control in a random sample of New Zealand adolescent asthmatics.
AB  - Asthma control, defined by asthma symptoms and lung function, and asthma
      medication use, was assessed in 123 adolescent asthmatics. Sputum eosinophilia
      (>or= 2.5% eosinophils) and bronchial hyperresponsiveness (BHR) to hypertonic
      saline were also measured to assess whether these additional objective parameters
      might aid in determining asthma control; 54.5% of subjects had adequately
      controlled asthma; 50.4% of all subjects reported inhaled corticosteroid use in
      the preceding 12 months; however, only 22.3% reported regular use. Although BHR
      and median eosinophil numbers were significantly higher in the inadequately
      controlled asthmatics, BHR and sputum eosinophilia had poor sensitivity for
      detecting inadequate asthma control.

PMID- 17530524
TI  - The use of oscillometry as a measure of airway responsiveness in asthmatic
      children after histamine and methacholine bronchoprovocation with dosimeter
      MedicAid and DeVilbiss nebulizers.
AB  - To explore the use of oscillometry as a measure of airway responsiveness, 69
      asthmatic children underwent histamine and methacholine bronchoprovocation using
      dosimeter-MedicAid (Jaeger Co.; Germany) and DeVilbiss nebulizers (DeVilbiss,
      Bornemouth; England). The mean increase in R5 resistance in challenge testing
      measured after methacholine with the dosimeter-MedicAid nebulizer was 77.14%
      compared with 65.05% using histamine. Using the dosimeter-DeVilbiss nebulizer,
      the mean increases in R5 resistance following methacholine and histamine testing
      were 57.50% and 59.36%, respectively. The resistance R5 over R20 significantly
      correlated with forced expiratory volume in 1 second (FEV1). The MedicAid
      produced a more aggressive challenge than the DeVilbliss nebulizer. Oscillometry
      can be used to monitor the level of airway hyperresponsiveness following
      bronchoprovocation tests.

PMID- 17530525
TI  - Effect of clinical pathways on the management of acute asthma in the emergency
      department: five years of evaluation.
AB  - There is a wide variability in clinical practice for treating acute asthma (AA)
      in the emergency department (ED), interfering in the quality of care. The purpose
      of this study was to evaluate the impact of a clinical pathway on the management
      of AA in the ED. We conducted a prospective before-after study of patients
      presenting with AA to the adult ED, during five separate periods (from January to
      March): in 2001 (pre-protocol group), 2002, 2003, 2004, and 2005 (6 months
      without educational reinforcement). We evaluated the effects of the
      recommendations on objective assessment of severity, diagnostic resource
      utilization, use of recommended and non-recommended therapy, and outcomes. The
      2001, 2002, 2003, 2004, and 2005 groups comprised, respectively: 108, 96, 97, 98,
      and 101 patients. There was a significant increase in the use of pulse oximetry
      (8.3%, 77.1%, 88.7%, 95.9%, and 97.0%, respectively; p < 0.001). There was an
      increase in the use of peak expiratory flow rate from 2001 to 2004 (4.6%, 20.8%,
      28.9%, and 48.0%) and a decrease after a period without educational efforts
      (29.7%, p < 0.001). Although the overall use of systemic corticosteroids was not
      changed, there was a significant increase in the use of oral steroids (p <
      0.001). There was a decrease in aminophylline utilization (p = 0.005). Length of
      stay in the ED was significantly reduced (p = 0.04). There was no effect on
      hospital admission or emergency discharge (p = 0.193). The AA clinical pathway
      applied in the ED was associated with a positive effect on improving the quality
      of care.

PMID- 17530526
TI  - Asthma remission in a patient with rheumatoid arthritis while on antiangiogenesis
      therapy during a rheumatoid arthritis trial demonstrated by forced oscillation
      and spirometry.
AB  - Asthma is a chronic inflammatory condition. An integral part of the inflammation
      is angiogenesis (neovascularization). This report describes a patient with
      rheumatoid arthritis (RA) and moderately severe asthma despite maintenance on
      inhaled corticosteroids (ics) and intermittent systemic steroids (ss). While
      enrolled in a clinical trial for RA employing MEDI-522 (Vitaxin), her asthma
      symptoms remitted substantially, with significant improvement in spirometry and
      airflow resistance measured by forced oscillation. The patient was able to
      discontinue ics and required no ss while taking MEDI-522. After termination of
      the clinical trial, the patient's asthma symptoms again increased and required
      reinstitution of ics for control.

PMID- 17530527
TI  - Pediatric asthma admissions: chronic severity and acute exacerbations.
AB  - Factors resulting in intensive care unit (ICU) admissions for asthma
      exacerbations remain largely unclear. We compared ICU and general pediatric ward
      admissions for asthma exacerbations. Charts of 56 (2- to 18-year-old) patients
      admitted consecutively to the ICU during a 1-year period for asthma exacerbations
      were compared with charts of 56 age-, sex-, race-, and era-matched patients
      admitted to a general pediatric ward. Few patients in both groups received oral
      steroids before admission. Children with different chronic asthma severities had
      comparable severities of acute exacerbation. In conclusion, acute asthma
      exacerbations dissociate in severity from chronic asthma and are under-treated
      with systemic corticosteroids.

PMID- 17530528
TI  - Prospective study of short stature and newly diagnosed asthma in women.
AB  - The authors tested the hypothesis that short stature predicts adult-onset asthma
      independent of obesity among women in the Nurses' Health Study. Height, weight,
      and physician-diagnosed asthma were assessed with validated questionnaire items.
      Proportional hazard models adjusted separately for weight and body mass index.
      The rate of newly diagnosed asthma was 1.55 times greater in the shortest versus
      the tallest quintile after adjustment for weight (95% CI, 1.26-1.91). After
      adjustment for body mass index, the rate ratio was 1.16 (95% CI, 0.94-1.42).
      Short stature predicted adult-onset asthma in a large cohort of women, but this
      association was not independent of obesity.

PMID- 17530529
TI  - Variation in adult asthma prevalence in Hispanic subpopulations in New York City.
AB  - BACKGROUND: We compared asthma prevalence among New York City Hispanics-Puerto
      Rican, Dominican, and other Hispanics-in relation to nativity, socioeconomic
      status, and asthma risk factors. METHODS: Weighted logistic regression analyses
      on telephone survey data for New York City (NYC) adults in 2003/2004. RESULTS:
      Asthma prevalence was highest among Puerto Ricans (11.8%) compared with
      Dominicans and other Hispanics. Non-US-born Dominicans and other Hispanics were
      significantly less likely to report current asthma than were Puerto Ricans (OR =
      0.27, 95% CI 0.18-0.41 and OR = 0.17, 95% CI 0.11-0.26, respectively). In
      multivariate analyses, US-born Dominicans and other Hispanics had rates
      comparable to Puerto Ricans. CONCLUSIONS: Puerto Ricans, both mainland- and
      native-born, report the highest rates of adult asthma. Non-US-born Hispanics
      report lower rates. Acculturation and patterns of residential settlement may
      account for this variation.

PMID- 17530530
TI  - The safety and efficacy of zileuton controlled-release tablets as adjunctive
      therapy to usual care in the treatment of moderate persistent asthma: a 6-month
      randomized controlled study.
AB  - This study was conducted to assess the safety and efficacy of zileuton controlled
      release [CR] 1,200 mg BID added to usual care (UC) in 926 patients with moderate
      asthma (619 patients randomized to zileuton CR and 307 to placebo). Sustained
      improvements in AM and PM peak expiratory flow (PEF) were observed in the
      zileuton CR group compared to placebo. The adverse event profile was similar in
      the two treatment groups. Eleven patients (1.8%) receiving zileuton CR and 2
      (0.7%) receiving placebo experienced elevations of alanine aminotransferase (ALT)
      >or= 3X the upper limit of normal (ULN). These elevations typically occurred
      (81.8%) during the first 3 months of exposure and most resolved within 21 days
      after discontinuation.

PMID- 17530531
TI  - Assessing the Perceived Stress Scale for African American adults with asthma and
      low literacy.
AB  - The Perceived Stress Scale (PSS) is a widely used measure of stress that has not
      been validated in asthma patients. The psychometric properties of the PSS were
      explored using confirmatory factor analysis and item response theory. Study 1
      involved 312 ambulatory care patients with asthma who completed the PSS during a
      routine visit. Study 2 involved 247 community-dwelling adults with asthma who
      completed the PSS as a part of a larger asthma study. Four items showed
      acceptable psychometric performance across ethnic groups and literacy. The short
      PSS is a rapid, valid measure of subjective stress in diverse asthma populations.

PMID- 17530532
TI  - The dietary habits of non-asthmatic schoolchildren in Lhasa, Tibet.
AB  - The occurrence of asthma symptoms and food consumption frequencies in 13- to 14
      year-old schoolchildren was investigated in Lhasa, Tibet (3,658 meters above sea
      level). A total of 99.2% of the schoolchildren reported that they had not
      experienced any wheezing during the prior 12 months. Among these students, more
      than 50% had consumed rice, meat, fruits, and vegetables at least three times per
      week in the preceding year. More than 70% of the non-asthmatic students rarely
      consumed margarine; 50% of these students rarely ate fast food; and 40% only
      occasionally ate fish during the prior 12 months. The dietary habits of the
      schoolchildren in Lhasa may have some potential beneficial roles in contributing
      to the low prevalence of asthma in this high altitude region.

PMID- 17530533
TI  - Reported respiratory symptoms and adverse home conditions after 9/11 among
      residents living near the World Trade Center.
AB  - This study investigated whether self-reported damage, dust, and odors in homes
      near the World Trade Center (WTC) after September 11, 2001, were related to
      increased rates of respiratory symptoms among residents and if multiple sources
      of exposure were associated with greater health risk. We mailed questionnaires to
      homes within 1.5 km of the WTC site (affected area) and in upper Manhattan
      (control area). Surveys asked about respiratory symptoms, unplanned medical
      visits, physician diagnoses, medication use, and conditions in the home after
      9/11. Adverse home conditions were associated with new-onset (i.e., began after
      9/11) and persistent (i.e., remained 1 year after 9/11) upper and lower
      respiratory symptoms in the affected area (Cumulative Incidence Ratios [CIRs]
      1.20-1.71). Residents reporting longer duration of dust/odors or multiple sources
      of exposure had greater risk for symptoms compared to those reporting shorter
      duration and fewer sources. These data suggest that WTC-related contamination in
      the home after 9/11 was associated with new and persistent respiratory symptoms
      among residents living near the site. While we cannot eliminate potential biases
      related to self-reported data, we took strategies to minimize their impact, and
      the observed effects are biologically plausible.

PMID- 17530534
TI  - Measuring physical activity in asthma patients: two-minute walk test, repeated
      chair rise test, and self-reported energy expenditure.
AB  - Although prudent exercise is recommended for most patients with well-controlled
      asthma, many patients avoid exercise and physical activity because they are
      concerned about triggering asthma. In a sample of 258 asthma patients (mean age
      42 years, 75% women), the objectives of this study were to assess the two-minute
      walk test and the repeated chair rise test and to compare results to self
      reported physical activity recorded with the Paffenbarger Physical Activity and
      Exercise Index (PAEI). Patients walked a mean of 510 feet, required a mean of 14
      seconds for the chair rise test, and reported a mean of 1,810 kilocalories per
      week from activities, mostly walking. In multivariable analysis, male sex,
      younger age, more education, lower body mass index, and better short-term asthma
      control, but not long-term asthma severity, were associated with better
      performance-based test results and more self-reported physical activity. Better
      short-term control also was associated with less breathing and leg exertion
      during both tests. Correlations between the PAEI and performance-based tests were
      approximately 0.38. Performance-based and self-reported measures provide
      information about various aspects of exercise capacity and can be used during
      routine clinical practice to assess physical activity in asthma patients.

PMID- 17530535
TI  - Predictors of asthma control in a random sample of asthmatic patients.
AB  - The purpose of this study was to identify determinants of asthma control.
      Questionnaires were completed by a random sample of 570 members of a large
      managed care organization who were >or=35 years of age with utilization
      suggestive of active asthma. Asthma control was assessed buy the Asthma Control
      Test (ACT). Independent relationships were found between lower ACT scores and
      oral corticosteroid use (p < 0.0001), COPD (p < 0.0001), absence of regular
      specialist care (p = 0.006), higher BMI (p = 0.01), gastroesophageal reflux (p =
      0.02), not being Caucasian (p = 0.04), and low income (p = 0.04).

PMID- 17530536
TI  - High background levels of urinary benzene metabolites found in a volunteer study.

PMID- 17530537
TI  - Developmental sequences of two-handed catching: how do children with and without
      developmental coordination disorder differ?
AB  - The present study examined the movement patterns in children with developmental
      coordination disorder (DCD) and their age-matched controls (AMC) while catching
      two-handed. First, a cross-sectional study was conducted to investigate
      developmental characteristics within the three body component actions (arm, hand,
      and body) of two-handed catching hypothesized by Haywood and Getchell (2005).
      Data analyzed from 36 children (18 DCD, 18 AMC) aged 7-10 years who caught a ball
      10 times, two-handed, showed that hypothesized sequences for the arm, hand, and
      body met the prelongitudinal screening criteria proposed by Roberton (1978),
      Langendorfer (1982), and Roberton, Williams, and Langendorfer (1980). In light of
      this, the second part of the study used these sequences to evaluate the movement
      patterns of 10 children with and 10 without DCD, aged 7-8 years. The data
      revealed that children with DCD displayed less advanced modal developmental
      sequence levels than AMC children with respect to the arm and body action
      components. (p <or= 0.01) Children with DCD also exhibited less advanced
      developmental profiles than the AMC children (p <or= 0.05), the group modal
      profiles being A2-H2-B2 and A3-H3-B3, respectively. These data also show that
      each child with DCD exhibited more developmental profiles over the 30 trials than
      the AMC children (p <or= 0.01) and that each DCD child's modal developmental
      profile was unstable (Roberton, 1977). Thus, over trials children with DCD link
      together different action patterns of the arm, hand, and body, suggesting that
      they have not yet developed a stable pattern of coordination to satisfy the task
      constraints.

PMID- 17530538
TI  - An evaluation of a framework for facilitating and assessing physiotherapy
      students' reflection on practice.
AB  - Reflective practice is promoted in the health care professions as a developmental
      process leading to competent and effective practice, although the link between
      reflection and enhancement of physiotherapy practice remains speculative and
      conjectural. This article provides evidence that reflection can influence
      developing practice based on the evaluation of a reflective framework for
      students on clinical placement. The evaluation explored, in depth, students'
      experiences and perceptions of its benefits and limitations. Thematic analysis of
      response data from five focus groups (n = 43) representing three student cohorts
      resolved significant outcomes-related themes: personal insight, linking
      reflection to the physiotherapy process, and learning and personal change.
      Process-related themes focused on strengths and weaknesses of the framework and
      associated issues. Evidence supports the effectiveness of the framework in
      facilitating reflection and in linking reflection to higher order cognitive
      processes such as gaining new insights and understandings, facilitation of
      systematic enquiry, problem solving, and decision making. Feedback from students
      indicated that the experience was meaningful and valuable in preparation for
      practice because they were guided to question themselves and could see the
      relevance and value of that for their practice. We recommend that educators
      consider this approach to facilitating reflection in physiotherapy undergraduate
      education.

PMID- 17530539
TI  - Clinical supervision as an interaction between the clinical educator and the
      student.
AB  - The interaction between clinical educators and students is regarded as the
      strongest element in developing expertise and in forming students' professional
      identity in clinical education. Although clinical education has been studied in
      physiotherapy, the natural interaction between clinical educators and students
      has remained unanalyzed. The aim of this study was to examine how supervised
      learning sessions during patient treatment were constructed. The focus was on the
      forms of interaction between clinical educators and students in natural contexts.
      By videotaping 12 natural patient treatment sessions, which simultaneously
      comprised part of the clinical education of physiotherapy students, and by using
      qualitative discourse analysis, three supervision discourses emerged from the
      data: "directing the interaction," "making limited room for the student," and
      "encouraging the student's participation." This study revealed that clinical
      educators have a dominant role in constructing supervised learning sessions
      during patient treatment. Depending on how the interaction is constructed, it is
      possible to support or prevent student participation in decision making as well
      as to promote or reject the rehearsal of critical thinking or self-directed
      learning among students. This study highlighted the importance of interactional
      skills in supervision practices. More research into constructing learning
      sessions in clinical education is needed.

PMID- 17530540
TI  - Use of music during physical therapy intervention for an infant with Erb's palsy:
      a single-subject design.
AB  - Evidence supporting the use of music during pediatric physical therapy
      intervention is limited. The purpose of this single-subject design was to
      evaluate the effects of music on patient progress, the amount of crying during
      therapy, and parent satisfaction with physical therapy services. The subject was
      an infant girl with Erb's palsy who participated in this study from age 8 months
      to age 20 months. An A-B-A withdrawal single-subject design was used. The
      patient's progress was assessed by using the T.I.M.E. The amount of crying was
      documented in the Crying Log. A parent satisfaction questionnaire was
      administered three times over the course of the study. The subject's progress in
      the music intervention period increased on three of five primary subtests of the
      T.I.M.E. The amount of crying decreased and parent satisfaction increased when
      music was played during therapy. Music may be used by pediatric physical
      therapists to decrease the patient's crying, increase parent satisfaction, and
      possibly to increase the child's rate of progress. Further research conducted
      with a group of infants and toddlers may help generalize these findings to a
      wider patient population.

PMID- 17530541
TI  - The reliability of hand-held dynamometry in measuring isometric strength of the
      shoulder internal and external rotator musculature using a stabilization device.
AB  - Although hand-held dynamometry is considered an objective method of measuring
      strength, the reliability of the procedure can be compromised by inadequate
      tester strength and insufficient stabilization of the dynamometer and subject.
      The purpose of this study was to investigate the test-retest reliability of a
      hand-held dynamometer with the use of a portable stabilization device while
      testing the shoulder internal and external rotator musculature. The isometric
      strength of the shoulder rotator musculature was tested twice in 30 asymptomatic
      adult volunteers (15 male and 15 female) between 18 and 63 years of age by using
      an intrasession design. Consistency of the testing protocol was maintained
      through the use of an arm stabilization apparatus, which fixed the arm in 30
      degrees of the scapular plane and a portable dynamometer stabilization device.
      Intraclass correlation coefficients (ICC's) were high, ranging from ICC (3,1) =
      0.971-0.972 for the test-retest trials of internal and external rotation. There
      was no significant difference between sessions one and two for maximum internal
      rotation (p = 0.431) and maximum external rotation strength (p = 0.780). The
      results indicate that the testing protocol with stabilization device is a
      reliable method for measuring strength of the internal and external rotator
      shoulder musculature.

PMID- 17530542
TI  - Ageing - a cross-cutting research and policy challenge.

PMID- 17530543
TI  - Humour, beauty, and culture as personal health resources: experiences of elderly
      Swedish women.
AB  - AIM: This paper explores how a group of elderly women used humour, beauty, and
      cultural activities to maintain physical and mental well-being. METHODS: The
      paper reports on one aspect of a qualitative study on women's work and health in
      a lifetime perspective. Interviews with 20 strategically selected Swedish women,
      aged 63 to 83 years, were audiotaped and analysed according to a phenomenological
      approach. RESULTS: During the interview process, the researchers became
      increasingly aware that the women had clear ideas about what enabled them to feel
      well and healthy - even when actually quite diseased. Creating and enjoying
      humour, beauty, and culture formed part of such strategies. Joking with workmates
      made hard, low-status jobs easier, helped them endure pain, and helped balance
      marital difficulties. Creating a nice and comfortable home gave pleasure and a
      little luxury in a life filled with necessities. Making articles for everyday use
      more beautiful was regarded as worthwhile, because it gave delight to them and
      their families. Gains from cultural activities were social, aesthetic, and
      existential - the latter through a feeling of self-recognition and being heard.
      CONCLUSIONS: Humour, beauty, and culture formed a greater part of these women's
      survival strategies than expected. Making everyday life more aesthetic is an
      undervalued aspect of women's health-creating work in the family. Through their
      lifelong experience as carers and homemakers, elderly women possess special
      knowledge regarding what may promote health, a knowledge that should be tapped.
      When supplying elderly women with social care, their needs for humour, beauty,
      and culture should be respected.

PMID- 17530544
TI  - Health-related physical fitness among schoolchildren in Lithuania: a comparison
      from 1992 to 2002.
AB  - AIM: Socioeconomic transformation over the previous decade may have created a
      less active lifestyle and a decline in fitness among Lithuanian children. The aim
      of this study was to analyse the differences in health-related fitness among 12-,
      14-, and 16-year-old Lithuanian boys and girls from 1992 to 2002. METHODS: The
      height and weight of the children were measured, and the Eurofit test battery was
      used to analyse the children's fitness. For the analyses of differences, 2,009
      children aged 12 (n = 697), 14 (n = 733), and 16 (n = 579) years were tested.
      RESULTS: Boys and girls of all three age groups performed better in the sit and
      reach test (12.4-19.8%, p<0.001) and in the 20 m shuttle run test (30.0-46.0%,
      p<0.001) but did fewer sit-ups (3.5-7.3%, p<0.05) in 1992 compared with the
      results in 2002. The girls' performance was better in the long broad jump test
      (4.9-5.5%, p<0.001) in 1992 than in 2002. These differences were not
      significantly influenced by weight, body mass index (BMI), and "height+BMI".
      CONCLUSIONS: There was a marked decrease in aerobic fitness and flexibility and a
      slight increase in abdominal muscle endurance among Lithuanian schoolchildren.
      Leg muscular power decreased slightly in girls but remained unchanged in boys. A
      decrease in daily physical activity is the most likely contributing factor to the
      decrease in aerobic fitness and flexibility and PE reform has not been able to
      compensate for this effect.

PMID- 17530545
TI  - Eight-year change in functional ability among 70- to 95-year-olds.
AB  - AIM: To describe stability and change in functional ability among non
      institutionalized old people in relation to sex, age, and household composition
      during two subsequent four-year observation periods. The study describes
      stability and change in total functional ability as well as in specific daily
      activities. METHODS: The study population included a random sample of non
      institutionalized 70+-year-olds studied in 1986 with follow-up in 1990 and 1995.
      The number of participants in the three surveys were 1,231 (participation rate
      67%), 911 (90% of 1,008 survivors), and 542 (77% of 706 survivors). Functional
      ability was measured at all three surveys. There is a considerable health
      selection from survey 1 to 2 to 3 because of a high mortality among participants
      with poor health. RESULTS: The proportions with unchanged, improved, and
      deteriorated functional ability were 51%, 13%, and 37% during the first four
      years and 50%, 9%, and 42% during the following four years. These changes were
      not related to age and sex. Major variations were seen with regard to change in
      individual daily activities with most deterioration in mobility and the more
      outgoing IADL activities (Instrumental Activities of Daily Living). Relatively
      large proportions of elderly people demonstrated at the same time improvements in
      some functions and deterioration in others. CONCLUSIONS: A notable minority of
      the population improved in functional ability and a large proportion was stable
      over time. These observations suggest a potential for health promotion among
      elderly persons, which up to now has been more or less neglected in health
      policy.

PMID- 17530546
TI  - Patient, clinician, and general practice factors in long-term certified sickness.
AB  - AIMS: To investigate the association of patient, clinician, and general practice
      factors with long-term certified sickness absence. METHODS: Analysis of a
      sickness certification database constructed via the use of carbonized sick notes
      by clinicians at nine general practices in the north-west of England. A total of
      3,385 patient sickness episodes certified by 44 general practitioners (GPs) were
      included in the analysis. Three logistic regression models were constructed in
      order to estimate independent effects of the patient, GP, and the general
      practice on risk of long-term (>28 weeks) incapacity. RESULTS: The logistic
      regression models explained a maximum of 27% of the variation in long-term
      certified sickness. The diagnostic reason for the sickness episode explained over
      18% of variance, while clinician and general practice effects explained only 3.4%
      and 2.3% respectively. In all models, older patient age and an episode within the
      mild mental disorder (MMD) diagnostic category significantly increased the risk
      of long-term work incapacity. CONCLUSIONS: The study results imply that, rather
      than basing 'return to work' interventions on identification of individual
      patient/claimant characteristics or on GP training initiatives, it may be more
      productive to focus upon a more diagnosis-based approach within primary care
      itself. Interventions aiming to reduce mild mental disorder-related work
      incapacity should be given priority.

PMID- 17530547
TI  - Birth-spacing patterns in Huaning County, Yunnan Province, PRC: is the adoption
      of a small family norm sustainable?
AB  - China's family planning programs have emphasized delayed marriage and longer
      spacing between births. Since 1970, the fertility has declined from 6 to 1.8
      births and the mean age at first marriage has gone up but the recommended spacing
      intervals have not been fully realized. Despite the fertility decline it is being
      debated among scholars whether China has completed a sustainable demographic
      transition or not, especially in rural areas. The aim of this study was to
      analyze trends in the timing and patterns of marriage and childbearing in
      relation to successive family planning policies. A cluster random sample of 1,336
      women aged 15-64 at the time of the survey (2000) was selected in one rural
      county in Yunnan province. Life-table techniques were used to analyze the
      cumulative proportion of women marrying and having a certain number of births.
      Cox's hazard regression model was used to estimate the effects of various
      covariates on the "hazard" for a woman to have a second birth. Our findings
      demonstrate how childbearing patterns have changed in the direction of delayed
      marriage, a decreased interval between first marriage and first child, and
      significantly longer spacing between the first and second child. This
      transformation of childbearing patterns corresponds well with the requirements of
      the policies. Considering the characteristics of Yunnan, it seems likely that the
      changing fertility behavior has been more influenced by a strictly enforced
      family planning policy than by societal changes leading to the adoption of a new,
      smaller family norm.

PMID- 17530548
TI  - The impact of psychosocial work conditions on attempted and completed suicide
      among western Canadian sawmill workers.
AB  - BACKGROUND: Using a large cohort of western Canadian sawmill workers (n =
      28,794), the association between psychosocial work conditions and attempted and
      completed suicide was investigated. METHODS: Records of attempted and completed
      suicide were accessed through a provincial hospital discharge registry to
      identify cases that were then matched using a nested case control method.
      Psychosocial work conditions were estimated by expert raters using the demand
      control model. Univariate and multivariate conditional logistic regression was
      used to estimate the association between work conditions and suicide. RESULTS: In
      multivariate models, controlling for sociodemographic (marital status, ethnicity)
      and occupational confounders (job mobility and duration), low psychological
      demand was associated with increased odds for completed suicide, and low social
      support was associated with increased odds for attempted suicides. CONCLUSIONS:
      This study indicates that workers with poor psychosocial working conditions may
      be at increased risk of both attempted and completed suicide.

PMID- 17530549
TI  - Smoking as a determinant of the geographical pattern of cardiac events among
      women in an urban population.
AB  - BACKGROUND: Smoking is the major risk factor for cardiac events in younger women
      and is most common in groups with the least favourable socioeconomic
      circumstances. OBJECTIVE: To assess to what extent geographical differences in
      the female incidence of myocardial infarction in the city of Malmo in Sweden can
      be accounted for by smoking and to what extent intra-urban variances of smoking
      are related to socioeconomic circumstances. METHOD: Area specific prevalences of
      smokers is based on a sample of 17,319 women, aged 45-73 years. A comprehensive
      score was used to rank the 17 residential areas in terms of socioeconomic
      circumstances. Incidence of myocardial infarction and death is based on official
      statistics 1989-97. RESULTS: The area-specific prevalence of female smokers,
      which ranged from 17.5 to 32.5%, was inversely related to the socioeconomic score
      in 45- to 54 and 55- to 64-year-olds, r = -0.65 (p<0.05) and -0.59 (p<0.05). No
      correlation was found for women above 65 years of age. The annual age-adjusted
      incidence of cardiac events in the residential areas, which ranged from 151 to
      414 per 100,000 person years, was strongly related to the prevalence of smokers,
      r = 0.75 (p<0.001). CONCLUSION: Between 50% and 60% of the intra-urban variance
      of the female incidence of myocardial infarction was accounted for by smoking in
      this urban population. The geographical pattern of smoking was strongly related
      to inferior socioeconomic circumstances.

PMID- 17530550
TI  - Unintentional injury mortality in the European Union: how many more lives could
      be saved?
AB  - AIMS: The wide variation of unintentional (accidental) injury mortality rates in
      the European Union (EU) member states suggests that there is high potential for
      prevention. This paper attempts to quantify the potential for saving lives in
      this part of the world if all 25 member states were to learn from the experience
      of countries with advanced injury prevention records. METHODS: Unintentional
      injury mortality data (latest three available years), including denominator
      population estimates, were obtained from the World Health Organization (WHO)
      mortality database for all 22 EU countries with a population of more than one
      million. Annual average age-adjusted injury mortality rates were used to derive
      the potential for saving of lives under two scenarios: (a) if all EU member
      states matched the country with the lowest unintentional rate for all causes of
      injury combined; (b) if the benchmark was alternatively the country with the
      lowest unintentional injury cause-specific rate. Separate calculations were
      performed for children (0-14), adults (15-64), and the elderly (65 and over).
      RESULTS: Under the first scenario, over 73,000 lives could have been saved in the
      EU 25 in a single year, notably nearly half (47.4%) fewer unintentional injury
      deaths could be observed in children, over half in adult (54%), and two-fifths
      (38%) in the elderly. Under the second, more optimistic, scenario 59% of
      childhood and adult and 75% of unintentional injury deaths among the elderly
      would have been avoided. CONCLUSIONS: A substantial proportion of lives lost due
      to unintentional injury might be saved if all countries were to achieve the
      lowest unintentional injury mortality rates in the EU. The above calculations are
      based on a simple theoretical model but there is increasing evidence on the array
      of existing effective preventive interventions and improved trauma care calls for
      public health action in each member state that could in practice halt, to the
      extent possible, the unintentional injury epidemic.

PMID- 17530551
TI  - Socioeconomic determinants of infant mortality: a worldwide study of 152 low-,
      middle-, and high-income countries.
AB  - BACKGROUND: To reach the Millennium Development Goals for health, influential
      international bodies advocate for more resources to be directed to the health
      sector, in particular medical treatment. Yet, health has many determinants beyond
      the health sector that are less evident than proximate predictors. AIM: To assess
      the relative importance of major socioeconomic determinants of population health,
      measured as infant mortality rate (IMR), at country level. METHODS: National
      level data from 152 countries based on World Development Indicators 2003 were
      used for multivariate linear regression analyses of five socioeconomic predictors
      of IMR: public spending on health, GNI/capita, poverty rate, income equality
      (Gini index), and young female illiteracy rate. Analyses were performed on a
      global level and stratified for low-, middle-, and high-income countries.
      RESULTS: In order of importance, GNI/capita, young female illiteracy, and income
      equality predicted 92% of the variation in national IMR whereas public spending
      on health and poverty rate were non-significant determinants when adjusted for
      confounding. In low-income countries, female illiteracy was more important than
      GNI/capita. Income equality (Gini index) was an independent predictor of IMR in
      middle-income countries only. In high-income countries none of these predictors
      was significant. CONCLUSIONS: The relative importance of major health
      determinants varies between income levels, thus extrapolating health policies
      from high- to low-income countries is problematic. Since the size, per se, of
      public health spending does not independently predict health outcomes,
      functioning health systems are necessary to make health investments efficient.
      Potential health gains from improved female education and economic growth should
      be considered in low- and middle-income countries.

PMID- 17530552
TI  - Sexual health among young adults in Finland: assessing risk and protective
      behaviour through a general health survey.
AB  - OBJECTIVE: To describe the extent of sexual risk and protective behaviours and
      reproductive health outcomes comparing men and women of 18-29 and assess the
      demographic correlates of these indicators within genders. DESIGN: A module of
      questions on sexual behaviour and reproductive health outcomes was integrated
      into a population-based general health survey in Finland. METHODS: A
      representative sample of people over 17, including 1,894 individuals between 18
      and 29 years, was drawn from the population registry in 2001. Individual
      interviews and self-administered questionnaires were used with a response rate of
      79% for the interview and 68% for the questionnaire. RESULTS: It was more common
      for younger men to stay single and have multiple partners while women of the same
      age were cohabiting or married and chose a regular sex partner. The mean number
      of sexual partner for men was 5.0 (SD 5.1) and for women 3.4 (SD 2.1). Besides
      higher prevalence of multiple partners, men reported also casual sex contacts
      more often than women, 33% vs. 20%. Both genders reported relatively high and
      concordant rates of contraception use. However, in casual sex contacts a condom
      was used consistently only by less than half of both sexes. Marital status was
      the strongest predictor for behaviour and health outcomes. CONCLUSIONS: Casual
      sex is common among young adults in Finland and often occurs without a condom.
      This study shows that it is feasible to incorporate sexual behaviour questions as
      part of a larger health survey offering an option for monitoring sexual behaviour
      when funding for large-scale HIV surveys is decreasing.

PMID- 17530553
TI  - Mortality in the Sami population of North Norway, 1970-98.
AB  - AIMS: The pattern of mortality among many groups of indigenous people has been
      shown to be disadvantageous in comparison with the general population. Knowledge
      regarding causes of death among the Sami population in the northern part of
      Norway is limited. The Sami constitute an ethnic minority whose lifestyle
      diverges from that of the rest of the population. METHODS: A cohort of 19,801
      persons of Sami origin was followed up to evaluate specific causes of mortality
      during the period 1970-98. Standardized mortality rates (SMR) were calculated
      using the rural population of the three Norwegian counties included in the study
      as a reference population. RESULTS: Among Sami, 5,955 total deaths were observed,
      as opposed to 5,537 expected (SMR = 1.08). For both Sami women and men a
      significantly higher SMR for cerebrovascular diseases was found, which was more
      pronounced for women. For Sami men, an excess SMR for violent death was observed
      (SMR 1.32, 95% confidence interval (CI) 1.20-1.46); this was highest among Sami
      men living in a reindeer-breeding family. For both genders, mortality from all
      malignant neoplasms combined was lower than in the reference population. SMRs
      were 0.86 (95% CI 0.79-0.94) and 0.89 (95% CI 0.80-0.99) for men and women,
      respectively. Low SMRs were also observed for chronic liver diseases, 0.18 (95%
      CI 0.02-0.63) and 0.12 (95% CI 0.00-0.68) for Sami men and women, respectively.
      To be a member of a reindeer breeding household appeared to offer protection from
      mortality caused by circulatory system diseases in men, especially mortality from
      ischaemic heart disease. CONCLUSIONS: The total mortality in the North Norway
      Sami population, an ethnic minority in Norway, was slightly higher when compared
      with a regional reference population. The differences observed when evaluating
      mortality by diagnosis might be due to lifestyle, diet, psychosocial, and/or
      genetic factors.

PMID- 17530554
TI  - Child health in Greenland.
AB  - AIM: To review the knowledge on child health and child health problems in
      Greenland. METHOD: The review was based on theses, national statistics, national
      and international reports, and a search in Pub Med, PsycINFO, Web of Science, and
      WHOLIB databases from 1985 to 2005. The resulting articles were sorted by topic,
      type, quality of study, and relevance for child health today, providing 47
      articles. RESULTS: Children in Greenland have become taller and have improved
      their general health. The morbidity found in Greenlandic children is similar to
      that found elsewhere even though the magnitude of problems might differ. The
      child mortality is relatively high and unevenly distributed. The acute disease
      pattern is dominated by infections, mostly airway infections. Otitis and its
      sequelae is a problem. An increase in chronic conditions such as atopy, asthma,
      obesity, and disabilities has taken place. Overweight and obesity have tripled in
      20 years and are a health threat as well as constituting negative health
      behaviour. Social ill health, socioeconomic inequity, and sociocultural changes
      also influence health but their consequences are not well investigated in
      children. CONCLUSIONS: A relatively high child mortality but the same morbidity
      pattern as in other Western societies was found. Negative health behaviour is
      frequent in schoolchildren. The influence of rapid cultural changes, and familial
      and societal factors related to social ill health, together with socioeconomic
      inequity, are of major importance to the health of children in Greenland. More
      accurate data on child health are necessary in the future to secure better
      prioritization. It is suggested to construct a set of reliable indicators of
      child health in Greenland to monitor the health of children on a national and
      regional basis.

PMID- 17530555
TI  - The Childcare Database: a valuable register linkage.
AB  - RATIONALE: To assess the impact of childcare attendance on morbidity for an
      entire country the Childcare Database was created by linking person-identifiable
      data from several Danish national data sources. The present paper describes the
      creation, characteristics, and potential of the Childcare Database. DESIGN AND
      MEASUREMENT: Based on the unique Danish Civil Registration System (DCRS)
      identification number register data were linked regarding childcare attendance,
      child and family characteristics, childcare facility characteristics, and
      hospitalizations for children aged 0 to 5 years in the period from 1989 to 2004.
      POPULATION AND SAMPLE SIZE: The number of children in the database increased in
      the period from 1989 to 1998 as more municipalities started registering
      childcare, whereafter it stabilized. The maximum number of children in the
      database was 373,142 in 2000. From 1999 to 2004 the Childcare Database covered
      more than 90% of all 0- to 5-year-old children in Denmark. At age 1 year 53% of
      children were enrolled in a childcare facility and approximately 75% were
      enrolled from 3 to 5 years of age. POTENTIAL: The Childcare Database offers a
      unique potential for epidemiological research within the area of childcare and
      morbidity. Future updates and linkages with other data sources will further
      expand the potential of the database. Due to the high quality of the linked
      nationwide register data, the Childcare Database enables conduction of
      epidemiological studies of high internal and external validity.

PMID- 17530556
TI  - Validation of the Abuse Screening Inventory (ASI).
AB  - AIMS: To assess the test-retest reliability and concurrent validity of the Abuse
      Screening Inventory (ASI) in a female sample. METHOD: The ASI comprises 16 items
      concerning four kinds of abuse: psychological, physical, and sexual abuse, and
      abuse in healthcare. A randomized sample of 699 women answered the ASI once. Six
      months later 53 of them answered the ASI again and were interviewed. To assess
      concurrent validity, answers in the interviews were considered as the gold
      standard and the ASI as the diagnostic test. RESULTS: The ASI presented good
      overall test-retest reliability ranging from 81% to 96% for separate items. The
      ASI separated very well abused from non-abused women. No false positive answers
      were found. Sensitivity ranged from 72% to 82% for items concerning abuse.
      CONCLUSION: The ASI is a short abuse screening questionnaire that had acceptable
      validity and test-retest reliability in a random female Swedish sample.

PMID- 17530557
TI  - NT-proBNP plasma levels and echocardiographic assessment of cardiac function in
      patients after renal transplantation.
AB  - BACKGROUND: Cardiovascular diseases are the most important causes of death in
      patients with chronic renal disease (CRD). Successful renal transplantation (RTx)
      corrects water and electrolyte disturbances and decreases or eliminates anaemia.
      It favourably influences cardiac haemodynamics and reduces risk of cardiovascular
      events. NT-proBNP plasma concentration is one of the prognostic and risk factors
      in such cases, whereas echocardiography that enables evaluation of the left
      atrium and ventricle allows detailed analysis of haemodynamic condition of the
      heart. AIM: To analyse NT-proBNP plasma concentration and selected
      echocardiographic parameters in patients after RTx at various time intervals
      after the procedure. METHODS: Seventeen patients after RTx were included in the
      study (age 46.5+/-16 years, 7 men and 10 women). NT-proBNP plasma level
      measurements and echocardiography were performed immediately before and at 3 and
      6 months after RTx. Additionally, these parameters were assessed in patients
      receiving cyclosporine A (CsA) and tacrolimus (TAC). RESULTS: NT-proBNP plasma
      level decreases significantly after RTx (initially 4369+/-2420, at 3 months
      2056+/-576, at 6 months 1580+/-572 pg/ml). In the TAC group, a significant
      reduction was observed at 3 months (from 13291+/-3563 to 1845+/-1022 pg/ml). In
      patients treated with CsA reduction occurred at 6 months after RTx (from 9447+/
      3369 to 1246+/-436 pg/ml). At six-month follow-up significant changes in ejection
      fraction were not found. However, a significant increase in LV mass in CsA
      patients was observed. CONCLUSIONS: Reduction of NT-proBNP levels seems to be
      more the result of transplanted kidney function than of an improvement in
      circulation. Significant LV mass increase in CsA patients may be a result of
      higher blood pressure levels observed before and after RTx.

PMID- 17530558
TI  - Impaired glucose tolerance worsens exercise capacity and ventilatory response to
      exercise in patients with chronic heart failure.
AB  - BACKGROUND: There is increasing evidence for the importance of peripheral
      abnormalities in the pathogenesis and progression of heart failure (HF).
      Recently, glucose and insulin metabolism abnormalities have been intensively
      investigated in patients with HF. AIM: To investigate whether coexistence of
      impaired glucose tolerance (IGT) may decrease exercise tolerance and influence
      ventilatory response to exercise in patients with systolic HF. METHODS: Maximal
      cardiopulmonary exercise test with evaluation of peak VO2 and VE/VCO2 slope and
      oral glucose tolerance test were performed in 64 clinically stable patients with
      HF and LVEF <45%. RESULTS: Impaired glucose tolerance was diagnosed in 26 (41%)
      patients and normal glucose tolerance (NGT) in 38 (59%) patients. There were no
      significant differences in baseline clinical characteristics or LVEF between
      groups. There were significant differences in peak VO2 between IGT and NGT
      (15.4+/-4.1 vs. 18.7+/-4.2 ml/kg/min respectively; p=0.003) and VE/VCO2 slope
      (35.7+/-7.3 vs. 31.8+/-5.7 respectively; p=0.02). The IGT was independently
      related to peak VO2 and VE/VCO2 slope in multivariate regression analysis.
      CONCLUSION: The IGT is associated with worse exercise capacity and ventilatory
      response to exercise in patients with HF.

PMID- 17530559
TI  - Effect of supervised integrated exercise on heart rate variability in type 2
      diabetes mellitus.
AB  - BACKGROUND: Heart rate variability (HRV) reflects autonomic nervous system
      modulation of cardiac activity. There is a relationship between degrees of
      physical activity, HRV changes and the risk of cardiovascular disease. AIM: To
      study the effect of a supervised integrated exercise programme on HRV in type 2
      diabetes mellitus (DM). METHODS: The study group consisted of 48 patients (27
      males, mean age 62+/-7 years) with type 2 diabetes, of whom 28 underwent a
      special exercise programme whereas the remaining 20 did not and served as the
      control group. The supervised integrated exercise programme was applied for a
      period of 9 months. Deep breathing time domain HRV (difference between the
      shortest and the longest R-R interval over one minute) was measured at baseline
      and after 3, 6 and 9 months. RESULTS: A significant improvement in the HRV values
      was observed with increasing duration of exercise (13.03+/-1.08 beats/min at
      baseline versus 16.5+/-1.11 beats/min at 9 months, p <0.001) whereas HRV
      decreased in the control group (14.85+/-1.15 beats/min at baseline vs. 14.30+/
      1.75 at 9 months, p <0.05). Favourable changes in HRV in the exercise group were
      gender-dependent and were significant in males (12.4+/-1.76 beats/min at baseline
      vs. 16.18+/-1.91 at 9 months, p <0.001) whereas in females only a trend towards
      HRV improvement was observed. The HRV changes were also age-dependent and were
      more pronounced in younger patients than in the elderly. The metabolic parameters
      of diabetes control (blood glucose and glycosylated haemoglobin levels)
      significantly improved in the exercise group and significantly worsened in the
      control group. CONCLUSIONS: Regular supervised integrated exercise significantly
      improves HRV in patients with type 2 DM, which may favourably influence their
      long-term prognosis.

PMID- 17530560
TI  - Minimally invasive off-pump video-assisted endoscopic surgical pulmonary vein
      isolation using bipolar radiofrequency ablation - preliminary report.
AB  - BACKGROUND: Atrial fibrillation (AF) is the most common arrhythmia, having a
      strong impact on long-term stroke and heart failure prevalence and mortality.
      Nowadays, rapid development in the field of minimising the invasiveness of
      surgical ablation of AF can be observed. AIM: To report on the feasibility and
      early results of the first Polish experience with a novel technique of minimally
      invasive video-assisted beating heart bilateral surgical ablation for lone
      paroxysmal AF using irrigated bipolar radiofrequency technique. METHODS: Between
      February and December 2006, 6 patients with highly symptomatic paroxysmal AF,
      resistant to pharmacological treatment, underwent video-assisted beating heart
      bilateral pulmonary vein isolation using irrigated bipolar radiofrequency
      combined with vein of Marshall dissection and left atrial appendage closure. In 2
      patients at least 2 unsuccessful percutaenous ablations had previously been
      performed. RESULTS: There were no complications. Ablation time was on average
      88+/-12.1 seconds. At least one recurrence of AF was observed in 4 patients in
      the early postoperative period; in 3 of them an electrical cardioversion was
      performed. All patients were discharged home in stable sinus rhythm. Three
      patients have exceeded 3 months' observation; one has reached 6 months of
      observation. All are in stable sinus rhythm and the follow-up course is
      uneventful. CONCLUSIONS: Minimally invasive video-assisted beating heart
      bilateral surgical ablation for lone paroxysmal AF using irrigated bipolar
      radiofrequency is effective and safe. These promising results have to be
      confirmed by larger studies.

PMID- 17530561
TI  - [Vascular anomaly - left anterior descending artery originating from right
      coronary sinus].
AB  - A case of a patient with congenital anomaly of coronary blood vessels with left
      anterior descending artery starting from right coronary sinus is presented. The
      patient was operated on due to symptoms of myocardial ischaemia by carrying out
      an off-pump coronary artery bypass graft to left anterior descending artery and
      obtuse marginal artery, with a very good outcome.

PMID- 17530562
TI  - [Long-term follow-up of a 35-year-old woman after myocardial infarction during
      pregnancy complicated by a pulmonary oedema - case report].
AB  - A case of a 35-year-old female who developed acute myocardial infarction and
      pulmonary oedema during pregnancy, is presented. Coronary angiography revealed a
      critical stenosis of the left circumflex coronary artery and a successful
      angioplasty was performed. The course of a subsequent 13 year follow-up was
      uneventful.

PMID- 17530563
TI  - [Hepatocellular carcinoma with metastases to the right atrium - case report].
AB  - The case of hepatocellular carcinoma with metastases to the right atrium is
      described. The most frequent tumors of the right atrium are discussed.

PMID- 17530564
TI  - [Acute inferior myocardial infarction with right ventricular involvement
      complicated by interventricular septum rupture - a case report].
AB  - A case of a 62-year-old female with acute inferior myocardial infarction with
      right ventricular involvement is presented. The patient developed cardiogenic
      shock due to interventricular septum rupture. Pharmacological agents and
      intraaortic balloon counterpulsation restored normal circulation which enabled
      elective surgical treatment 14 days after the onset of symptoms.

PMID- 17530565
TI  - [Atrial fibrillation: potential therapeutic interventions in the renin
      angiotensin-aldosterone system].

PMID- 17530566
TI  - [From complete atrio-ventricular block to ventricular fibrillation].

PMID- 17530567
TI  - [The role of transesophageal echocardiography in planning strategy of surgical
      treatment of aortic dissection].

PMID- 17530568
TI  - [Myocardial infarction and left coronary thrombosis with atypical coronary
      angiogram].

PMID- 17530569
TI  - [Presyncope caused by non-sustained ventricular tachycardia. Significance of RF
      ablation].
AB  - We describe a case of a 55-year-old man with episodes of presyncope caused by non
      sustained ventricular tachycardia (ns-VT). Symptoms of significant weakness
      started when he was 30-year-old. In the last 2 years there was a substantial
      increase in frequency of presyncope from 2 per month to 8 per week. He does not
      have palpitations. Standard ECG, echocardiography and coronary angiography were
      normal. During an exercise test ns-VT 220/min (5 s, 20 x QRS) with LBBB
      morphology was documented. Successful RF ablation of ns-VT using the CARTO system
      was performed. During 4-month follow-up the patient remains free from ventricular
      arrhythmia.

PMID- 17530570
TI  - [When and why aortic valve should be repair].

PMID- 17530571
TI  - Development of the stroke unit network in Poland--current status and future
      requirements.
AB  - BACKGROUND AND PURPOSE: According to the World Health Organization establishments
      and European Stroke Initiative recommendations, every patient with stroke should
      be treated by a specialized stroke team or in a specialized stroke unit. We aimed
      to evaluate the development of the stroke unit network in Poland and
      accessibility of stroke units in 2005. MATERIAL AND METHODS: Questionnaires
      evaluating structure and staff of neurological departments were sent to all
      neurological departments in Poland in the second quarter of 2005. We divided
      departments into the following categories: those having a class A stroke unit
      (fulfilling criteria of experts of the National Programme of Prevention and
      Treatment of Stroke) class B stroke unit (conditionally fulfilling those
      criteria), class C stroke units (not fulfilling the criteria), and departments
      without stroke units. The classification was presented to the chief consultant in
      neurology of each voivodship in December 2005 for verification of the data.
      RESULTS: We received enquiries from 180 out of 220 (81.8%) departments.
      Consultants included data of a further 8 departments which did not respond to the
      questionnaire (188 - 85.5%). 105 departments declared having a stroke unit (58
      class A units, 40 class B units, and 7 class C units). 83 other departments do
      not have stroke units. The most frequent problem that plays a role in
      classification of departments was the deficit of staff or lack of equipment. It
      is assessed that the supplementation of diagnostic equipment and staff in
      existing stroke units and the establishment of 27 new stroke units is required to
      satisfy current needs. CONCLUSIONS: The development of the stroke unit network in
      Poland is proceeding dynamically. There are 105 stroke units in Poland but 45% of
      them require additional diagnostic equipment and staff.

PMID- 17530572
TI  - CYP2D6 gene polymorphism as a probable risk factor for Alzheimer's disease and
      Parkinson's disease with dementia.
AB  - BACKGROUND AND PURPOSE: The theory of multifactorial inheritance is considered in
      the pathogenesis of sporadic Alzheimer's disease (AD) and Parkinson's disease
      (PD); therefore, it makes the genes regulating bioactivation or detoxification of
      exogenous substances candidates of sensitivity to Alzheimer's and Parkinson's
      diseases. The aims of the study were: 1) to determine the genotypes of CYP2D6
      cytochrome (CYP2D6) in patients with AD and sporadic PD with dementia; 2) to
      evaluate the relationship between the CYP2D6 genotype and the age of onset of the
      disease, the extent of dementia in AD and PD, the dose and side effects of L-dopa
      in PD; 3) to evaluate the usefulness of CYP2D6 genotyping in predicting
      predispositions to PD and AD. MATERIAL AND METHODS: 53 patients with AD aged 58
      84 (mean age 72.6) and 52 patients with PD with dementia aged 51-82 (mean age
      70.4) were recruited. Each AD patient satisfied criteria for probable AD.
      Diagnostic and Statistical Manual of Mental Disorders 4th edition, Mini-Mental
      State Examination, Clinical Dementia Rating Scale and Global Deterioration Scale
      were used for dementia evaluation in PD patients. Clinical scales for PD
      evaluation were used. Methods of molecular biology were used for genetic studies.
      RESULTS: There were no differences in CYP2D6 genotype and allele distribution in
      AD and PD patients. There was no relationship between CYP2D6 alleles and the age
      of onset and advancement of dementia in AD and PD. No relationship between CYP2D6
      alleles and the dose and side effects of L-dopa in patients with sporadic PD with
      dementia was observed. CONCLUSION: As there were no differences in CYP2D6
      polymorphism in AD and PD, CYP2D6 does not seem to be a factor predisposing to
      these diseases.

PMID- 17530573
TI  - Accuracy of intraoperative registration during electromagnetic neuronavigation in
      intracranial procedures performed in children.
AB  - BACKGROUND AND PURPOSE: The aim of the study was to evaluate registration
      accuracy in an electromagnetic navigation system applied to image-guided
      intracranial procedures in children. MATERIAL AND METHODS: In a group of 34
      children aged from 2 weeks to 17 years, 38 procedures were performed using
      electromagnetic navigation, including 24 neuroendoscopic procedures, 10
      craniotomies, and 4 shunting or drainage procedures. Thirty-three registrations
      based on 7 to 10 anatomical landmarks were digitised, and three-dimensional
      models of patients' heads were constructed using magnetic resonance images (MRI)
      (23 cases) or computed tomography scans (CT) (10 cases) and used for further
      analysis. Registration error calculated by the system was used as a measure of
      registration accuracy. RESULTS: Registration error in the study group ranged from
      0.7 mm to 4.4 mm (median 2.1 mm, mean 2.24 +/- 0.7 mm). It was shown that
      registration accuracy increased with patients' age. Differences between mean
      registration errors in procedures based on MRI or CT studies were not
      significant. There was no correlation between the number of landmarks registered
      and registration accuracy. CONCLUSIONS: Electromagnetic neuronavigation, which
      does not require firm head fixation, can be used in the youngest age group.
      Nevertheless, registration accuracy is lower in newborns and infants. Neither
      imaging modality (MRI or CT) used for creation of a three-dimensional model of
      the patient's head nor registration of more than 6 landmarks have an impact on
      registration accuracy.

PMID- 17530574
TI  - The assessment of gait disorders in patients with Parkinson's disease using the
      three-dimensional motion analysis system Vicon.
AB  - BACKGROUND AND PURPOSE: Gait disorders are a common symptom of Parkinson's
      disease (PD) and can occur in the early stage of the disease. The most
      characteristic gait disorders in that disease affect pace and cadence. This study
      was designed to assess spatiotemporal and kinematic gait parameters of patients
      with PD using the three-dimensional motion analysis system Vicon. MATERIAL AND
      METHODS: 32 patients (14 women and 18 men; age range: 50-75) treated for PD in
      the Department of Neurology were studied. The control group consisted of 32
      healthy persons (13 women and 19 men, age range: 52-77). Gait analysis using the
      Vicon 3D system took place in the Biokinetics Laboratory in the Academy of
      Physical Education in Krakow. The Vicon 3D system enables computerized
      registration and analysis of motion in three-dimensional space. RESULTS: The
      analysis of basic spatiotemporal parameters of gait revealed that PD patients had
      considerably lower walking speed, stride length and cadence and longer time of
      double support than controls. The assessment of kinematic gait parameters showed
      that PD patients had decreased motion range in the joints of the lower limbs and
      began the double support phase earlier and delayed the swing phase when compared
      to healthy controls. CONCLUSION: Our study shows a difference between PD patients
      and healthy controls at similar age both in angle changes and in spatiotemporal
      parameters of gait.

PMID- 17530575
TI  - Familial narcolepsy.
AB  - BACKGROUND AND PURPOSE: Narcolepsy is a disease characterized by chronic
      excessive daytime sleepiness with episodic sleep attacks. There are several
      associated symptoms of narcolepsy: cataplexy (bilateral muscle weakness without
      loss of consciousness, provoked by an emotional trigger, e.g. laughter), sleep
      paralysis (isolated loss of muscle tone associated with rapid eye movement [REM]
      in normal sleep) and hypnagogic-hypnopompic hallucinations (vivid dreaming
      occurring at the time of sleep onset and awakening that can be difficult to
      distinguish from reality). MATERIAL AND METHODS: The authors present eleven
      patients with suspected narcolepsy, who were members of a five-generation family
      with many cases of episodic excessive daytime sleepiness. Some of them
      experienced sleep attacks which were occasionally associated with a sudden loss
      of muscle tone (cataplexy), as well as with sleep paralysis and hypnagogic
      hallucinations. All probands had magnetic resonance (MR) of the brain performed,
      along with routine blood tests, EEG, polysomnography, examination of the level of
      hypocretin in the cerebrospinal fluid and evaluation by means of Epworth and
      Stanford Sleepiness Scales. RESULTS: Narcolepsy was diagnosed in nine patients.
      Improvement in their clinical state was observed during the treatment with
      modafinil.

PMID- 17530576
TI  - Value of Pelli-Robson contrast sensitivity chart for evaluation of visual system
      in multiple sclerosis patients.
AB  - BACKGROUND AND PURPOSE: The Multiple Sclerosis Functional Composite (MSFC) score,
      in addition to the commonly used EDSS scale, is one of the standard procedures
      used for a quantitative evaluation of the clinical state of patients with
      multiple sclerosis (MS). These methods, however, do not include an evaluation of
      the visual system. Hence, a search for sensitive tests evaluating the state of
      the visual system is important. Our study aims to answer the question whether the
      examination of contrast discrimination by means of the Pelli-Robson method is of
      any objective value for clinical practice. MATERIAL AND METHODS: 100 Patients
      presenting with MS and 29 healthy subjects with 100% visual acuity (assessed by
      means of Snellen's scale) were included in the study. The examination of visual
      acuity was performed by means of a contrast discrimination chart (Pelli-Robson)
      according to the instructions provided by the manufacturer. RESULTS: Contrast
      discrimination capacity was found to be significantly lower in the group of MS
      patients than that established in the control group. The same observation holds
      true for the subgroup of MS patients presenting with normal visual acuity,
      measured with the Snellen scale. Categorization of results showed that values
      <1.40 lg of contrast discrimination were not found in healthy subjects.
      CONCLUSIONS: The Pelli-Robson contrast discrimination test is a more sensitive
      procedure for detecting visual disturbances than the visual acuity test according
      to Snellen. The Pelli-Robson test thus constitutes a valuable supplement of the
      examination triad routinely involved in the MSFC for evaluation of the clinical
      status of patients, especially in the dynamic aspect of the outcome measure.

PMID- 17530577
TI  - Stroke-related seizures and epilepsy.
AB  - No guidelines exist concerning risk factors, diagnosis, management and treatment
      of stroke-related seizures. Seizures related to intracerebral haemorrhages occur
      in 10.6%, while those related to ischaemic stroke appear in 8.6%. Early-onset
      seizures have a poor prognosis with a high in-hospital mortality rate. They occur
      significantly more often in patients with haemorrhagic strokes. The recurrence
      rate is low. Late-onset seizures occur mainly between 6 months and 2 years after
      stroke with a high recurrence rate. Patients with a partial anterior circulation
      syndrome, a large cortical infarct with irregular borders, located in the parieto
      temporal regions, are mainly at risk. Post-stroke seizures are harmful and
      require treatment with antiepileptic drugs. Post-stroke EEG can help to predict
      those patients who are at risk of developing seizures. The difference between
      early- and late-onset seizures is arbitrary as 20% of seizures occurring in
      patients with a previous cerebral infarct are the clinical expression of a new
      stroke.

PMID- 17530578
TI  - Mitochondrial dysfunction in Parkinson's disease--revisited.
AB  - In recent years much of the research conducted in the field of Parkinson's
      disease (PD) has been aimed at trying to elucidate the molecular mechanisms
      involved in the development of the rare familial forms of the disease, with the
      hope that an understanding of these mechanisms will shed some light into the
      pathogenesis of the more prevalent idiopathic form of the disease. These studies
      have implicated mitochondrial dysfunction in the pathogenesis of familial PD,
      either as a primary event, with disease causing mutations identified in genes
      encoding mitochondrial proteins, or as a secondary event. Thus, the role played
      by mitochondrial respiratory chain function in the pathogeneis of idiopathic PD,
      an area of research that was a main focus some 15-20 years ago, has come back to
      the forefront of the field. A number of studies have directly investigated
      respiratory chain function in a variety of tissues from idiopathic PD patients.
      Although abundant in number, these studies have provided contradictory results,
      which still require clarification. In this review we will examine the data
      indicating the presence of a respiratory chain defect in patients with idiopathic
      PD and attempt to link it with the pathways that have been implicated by familial
      studies.

PMID- 17530579
TI  - [Deep brain stimulation of the ventral intermediate thalamic nucleus in the
      treatment of essential tremor].
AB  - Essential tremor (ET) is the most common movement disorder. In most patients the
      course of ET is mild and pharmacological therapy controls postural and kinetic
      components of tremor. The first-line treatment of ET is pharmacotherapy with
      propranolol, primidone and gabapentin. In patients with marked head and voice
      tremor, local botulinum toxin injections have been found to be very effective.
      Despite optimal drug therapies it is estimated that approximately 50% of patients
      with ET have medication-resistant tremor. ET can cause more functional impairment
      than parkinsonian resting tremor because most prominent components of ET are
      postural and kinetic ones. For patients with drug-resistant debilitating tremor,
      surgical therapy (thalamotomy) and more recently deep brain stimulation (DBS) of
      the ventral intermediate thalamic nucleus (VIM) is a viable treatment modality.
      Several long-term studies have confirmed the high effectiveness rate of ablative
      surgery and thalamic DBS in the treatment of ET. The most striking advantage of
      thalamic DBS is the possibility of performing bilateral surgery in one operative
      session with a significantly lower rate of side effects. Nowadays the bilateral
      staged thalamotomy is performed rarely because of unacceptable side effects.
      Moreover, many authors have observed that in bilaterally stimulated patients the
      head and voice tremor have diminished in postoperative course. Thalamic DBS is a
      very efficacious and safe procedure in the treatment of ET.

PMID- 17530580
TI  - [Acquired peripheral neuropathies associated with monoclonal gammopathy].
AB  - Monoclonal gammopathy is responsible for about 10% of acquired peripheral
      neuropathies of unknown origin. Monoclonal gammopathy is the result of
      uncontrolled proliferation of a single clone of plasma cells producing the first
      class of immunoglobulin (M-protein). The routine diagnostic process of peripheral
      neuropathy requires electrophysiological studies and several laboratory tests,
      including the immunoelectrophoresis or immunofixation of serum proteins.
      Monoclonal gammopathies develop in malignancy, immunological disorders, chronic
      infections and as so-called "benign form" or monoclonal gammopathy of
      undetermined significance (MGUS). Lymphoproliferative malignancy may develop in
      MGUS after many years of disease. Patients with MGUS-associated neuropathy should
      be carefully evaluated, and if malignancy is not found the progress of the
      disease should be monitored. We present four patients with peripheral neuropathy
      associated with monoclonal gammopathy. These cases represent different forms of
      this type of neuropathy and well illustrate the necessity of looking for
      monoclonal gammopathies in peripheral neuropathy.

PMID- 17530581
TI  - [Intraneural ganglion of the tibial nerve--a case report].
AB  - This paper describes a surgically treated case of gelatinous cyst of extremely
      rare location within the tibial nerve at the level of the popliteal fossa. The
      initial diagnosis was based on imaging exams (MRI, ultrasonography) and surgical
      exploration of the tumour. The intraneural ganglion was completely removed.
      Neurological motor and sensory deficits were observed neither in the preoperative
      nor in the postoperative period. The ultimate diagnosis was established based on
      the histopathological examination.

PMID- 17530582
TI  - [Migraine with visual aura: visual aura pictured by the patient].
AB  - The most frequent type of migraine aura is the typical one in which the most
      frequently occurring aura type are visual phenomena. Types of visual aura may be
      different. Scintillating scotoma, fortification zigzags (teichopsiae),
      fragmentation of the visual image are typical illusions in visual aura. The
      visual illusion of a typical corona phenomenon was represented as a visual
      migraine aura symptom. The extra edges of the corona phenomenon are commonly seen
      around the perceptual images of objects. The corona phenomenon is strongly
      associated with visual loss and the presence of elementary geometric illusions.
      It is surrounding a person's head, shoulders, hands, or body. Illusory splitting
      can be differentiated from the fragmentation of visual images and from the
      geometric illusion or mosaic illusion. The pathogenesis of migraine aura remains
      unclear. The probable cause of migraine aura may be cortical spreading depression
      (CSD) and cerebral hypoperfusion. Ionic changes, activation of trigeminal nerve
      and release of neuropeptides seem to be secondary to CSD during the attack of
      migraine aura. In present article the pictures of visual aura experienced by
      migraine patient are presented and discussed.

PMID- 17530583
TI  - [Median or mean?].

PMID- 17530584
TI  - [The 2 by 2 table].

PMID- 17530585
TI  - [What is the p-value?].

PMID- 17530586
TI  - [What is a confidence interval?].

PMID- 17530587
TI  - [What is a significance test? General issues].

PMID- 17530588
TI  - [Serial data curves].

PMID- 17530589
TI  - [Common significance tests].

PMID- 17530590
TI  - [Multiple testing].

PMID- 17530591
TI  - [Quantiles, cumulative distribution function, and box-plot].

PMID- 17530592
TI  - [Multiple regression].

PMID- 17530593
TI  - [Logistic regression].

PMID- 17530594
TI  - [Survival analysis: properties and Kaplan-Meier method].

PMID- 17530595
TI  - [Survival analysis: log rank test].

PMID- 17530596
TI  - [Survival analysis: Cox regression].

PMID- 17530597
TI  - [Common study designs in epidemiology].

PMID- 17530598
TI  - [Systematic reviews and meta-analyses].

PMID- 17530599
TI  - [Measures of variability].

PMID- 17530600
TI  - [Equivalence and non-inferiority trials].

PMID- 17530601
TI  - [Analysis of variance].

PMID- 17530602
TI  - [Analysis of variance for repeated measurements].

PMID- 17530603
TI  - [The kappa coefficient].

PMID- 17530604
TI  - [Comparing methods of measurement].

PMID- 17530605
TI  - [The histogram].

PMID- 17530606
TI  - [Linear regression and correlation].

PMID- 17530608
TI  - Long-term outcomes of flap transfer for treatment of intractable venous stasis
      ulcers in the lower extremity.
AB  - There is little information about long-term outcomes of flap transfer for
      treatment of venous stasis ulcers in the lower extremity. Eleven patients who
      underwent free and pedicled flap transfer for treatment of intractable venous
      stasis ulcers were evaluated retrospectively. The operative procedures consisted
      of removal of the ulcer and surrounding lipodermatosclerotic tissue, venous
      stripping, and flap transfer. No ulcer recurrences in the territory of the
      transferred flap were identified for a mean of 11 years during the follow-up
      period. However, four patients developed new ulcers in the same leg after the
      flap transfer at 18, 24, 52, and 81 months. This was probably the result of
      incomplete excision of surrounding lipodermatosclerotic tissue. Three of four
      recurrent ulcers were healed with additional procedures. The results of this
      study indicated that flap transfer combined with venous stripping could lead to
      long-term healing of venous stasis ulcers. However, incomplete excision of
      surrounding lipodermatosclerotic tissue caused new ulceration around the
      transferred flap.

PMID- 17530609
TI  - Combination of hypoglossal-facial nerve jump graft by end-to-side neurorrhaphy
      and cross-face nerve graft for the treatment of facial paralysis.
AB  - The cross-face nerve graft and the interpositional jump graft were performed
      simultaneously for 13 patients with facial paralysis. The period between the
      onset of paralysis and surgery ranged from 3 to 32 weeks. In nine patients,
      surgery was performed within 3 months of the onset of paralysis. The patients in
      whom reinnervation by both grafts succeeded could smile without closing their
      eyes by moving the tongue and could close the eye on the affected side without an
      accompanying oral movement. The expression was natural and included fine muscle
      movements. Spontaneous recovery of the facial nerve was observed in three
      patients. Among patients who showed functional recovery without spontaneous
      recovery, House-Brackman's palsy grade was II in one patient, III in five
      patients, and IV in one patient. Functional deficits of the tongue were not
      observed. We recommend that this surgery be performed within 3 months of onset of
      paralysis.

PMID- 17530610
TI  - Noninvasive tissue oximetry for flap monitoring: an initial study.
AB  - The ideal monitoring tool to evaluate free flap success should be noninvasive,
      continuous, and reliable. A new device, the ViOptix Tissue Oximeter (ODISsey)
      based on near-infrared spectroscopy was evaluated in 30 patients undergoing
      autologous tissue perforator free flap breast reconstruction with continuous
      monitoring of the flap during elevation, transfer, and the postoperative period.
      The device accurately reflected the ischemic drop in oxygen saturation during
      flap transfer, and the hyperemic response after flow was reestablished. There
      were no flap failures, but in two patients, the device indicated a venous
      thrombosis before it was clinically obvious and allowed for expeditious flap
      salvage. The noninvasive nature of the device, the ability to replace and move
      the probe in the postoperative period, and the measurement of end organ
      oxygenation are all advantages over other currently available techniques.

PMID- 17530611
TI  - The role of donor site angiography before mandibular reconstruction utilizing
      free flap.
AB  - This study was initiated to establish a treatment algorithm for preoperative
      evaluation of donor sites prior to the harvest of free osteocutaneous flaps, in
      the setting of complex mandibulofacial reconstruction. A total of 29 consecutive
      patients were treated between 1999 and 2003 in a university-based setting.
      Reconstructions were completed using either a free fibula osteocutaneous flap or
      a radial forearm free flap. Functional and aesthetic results were determined by
      completing a thorough patient physical examination postoperatively. We
      hypothesized that a routine preoperative angiogram at the donor site was
      unnecessary. The Allen's test was the only preoperative evaluation completed in
      the 13 patients undergoing the free radial forearm reconstruction. In the
      remaining 16 patients undergoing free fibula reconstruction, a thorough physical
      examination was completed, along with noninvasive Doppler examinations. No
      angiograms were obtained. Using this systematic approach, no ischemic
      complications were observed at the donor site. Only two complete flap losses were
      seen, one in each group, due to microvascular thrombosis. We conclude that
      preoperative assessment of the donor site(s) with only an Allen's test in the
      free radial forearm group and a thorough pulse exam and a noninvasive Doppler in
      the free fibula group appear adequate. Routine preoperative angiogram of the
      donor extremity may be unnecessary and place the patient at additional risk for
      associated complications.

PMID- 17530612
TI  - Magnetic resonance angiography for free fibula flap transfer.
AB  - Recent refinements of magnetic resonance angiography (MRA) allow imaging vessels
      as small as the septocutaneous perforators (< or = 1 to 2 mm diameter), but a
      Medline review reveals no report of septocutaneous vessel imaging for free flap
      surgery. Challenges in fibula free flap preparation include knowledge of: (1)
      tibioperoneal anatomy, (2) the positions of the perforator vessels on the
      peroneal artery and their course in the posterolateral intermuscular septum, and
      (3) the cutaneous distribution of the perforators. Questioning whether high
      resolution MRA could image these, we studied the lower extremities of nine
      healthy volunteers. MRA demonstrated tibioperoneal anatomy in sufficient detail
      to exclude anatomic variants and significant peripheral vascular disease and
      showed septocutaneous perforators arising from the peroneal artery and coursing
      in the posterolateral intermuscular septum to the skin. High-resolution MRA
      provided anatomic and clinical information that conventionally has been
      impossible to obtain preoperatively or has required multiple tests, often of an
      invasive nature.

PMID- 17530613
TI  - One-segment double vascular pedicled free jejunum transfer for the reconstruction
      of pharyngoesophageal defects.
AB  - The reported success rates of free jejunal transfer are over 95%, but in cases of
      postoperative vascular thrombosis, the salvage of jejunal flap is often difficult
      because of poor ischemic tolerance of the jejunum. To reduce the incidence of
      jejunal necrosis due to vascular thrombosis to nearly zero, we employed one
      segment double vascular pedicled free jejunal transfer. Different from
      conventional double pedicled free jejunal transfer (transfer of the two jejunal
      segments by anastomosing two pairs of jejunal root vessels), the arcade vessels
      are used as an additional feeder after the routine anastomosis of jejunal root
      vessels in our method. Between December 2004 and January 2006, 20 patients with
      laryngeal, pharyngeal, or cervical esophageal cancer underwent free jejunal
      transfer using this method. In all patients, the jejunal flap survived completely
      without any complication associated with vascular anastomosis or blood
      circulation of the flap. The disadvantage of this procedure is the approximately
      1-hour prolonged operative time. Although we have experienced only 20 cases and
      not obtained statistically significant validity of this method compared with
      conventional one, we believe that the concept of our method is one of the help
      for safer pharyngoesophageal reconstruction, especially in patients with higher
      risk of vascular thrombosis.

PMID- 17530614
TI  - Venae comitantes as a source of vein grafts.
AB  - The use of vein grafts is commonplace and often essential in microvascular
      surgery. Typically, these are obtained from the superficial venous system, and
      most commonly from the lower extremity using branches or segments of the greater
      or lesser saphenous veins. Unfortunately, on rare occasions these usual donor
      sites may have been totally exploited. This potential dilemma can be solved by
      using the deep venae comitantes as autogenous vein grafts. By way of example,
      these can be venae comitantes of the free flap itself, or via salvage of parts
      using a vena comitans that accompanied a major limb source vessel.

PMID- 17530615
TI  - Microsurgical reconstruction for radiation necrosis: an evolving disease.
AB  - We performed a retrospective chart review of a tertiary care medical center. Our
      objective was to report our experience with microvascular reconstruction in the
      head and neck in patients who presented with radiation-induced tissue damage. We
      will discuss the effects of radiation to soft tissues and bone in the head and
      neck as well as the challenges it presents for later free tissue transfer.
      Patients were identified who underwent free tissue transfer to the head and neck
      for radiation-induced tissue injury by the senior author at our institution. Data
      were collected to include location of the primary disease, radiation amount and
      zone of radiation injury, initial surgical reconstruction, time to development of
      radiation necrosis, type of free flap selected, recipient vessel selection, the
      number of sequential free tissue transfers, hyperbaric oxygen therapy, flap
      success rates, and minor complications. Patients were excluded if recurrent
      cancer was identified at any time following reconstruction. One hundred sixty-one
      free flaps were performed from 2000 to 2004 in the head and neck by the senior
      author at our tertiary care institution. Fourteen patients were identified who
      met the inclusion criteria and 16 (two lateral thigh, two iliac crest, one radial
      forearm, one transverse rectus abdominis, six fibula, two latissimus dorsi with
      associated rib, and two scapula) free flaps were performed for radiation-induced
      complications. Five patients required multiple sequential free flaps including
      the initial reconstruction. Anastomosis was performed within the radiation zone
      of injury in 14 cases (87.5%), whereas 2 (12.5%) were performed outside the zone
      of injury. Forty-three percent of patients ( N = 6) underwent hyperbaric oxygen
      therapy. After initial reconstruction, the incidence of complications requiring
      surgical intervention included skin breakdown ( N = 1), fistula ( N = 2), and
      persistent osteoradionecrosis ( N = 2). The mean time to follow-up was 17.5
      months (range 1 to 49). There was one partial flap failure that was salvaged by
      thrombectomy. There were no total flap failures. As primary treatment for head
      and neck cancer moves toward radiation therapy, microsurgical reconstruction is
      playing an increasing role for those patients developing radiation-related
      complications. Radionecrosis is a progressive disease where the incidence is
      increasing as patients are surviving longer. Understanding the effects of
      radiation on soft tissue and bone and the complexity of reconstruction in the
      zone of injury will greatly improve the success of reconstruction.

PMID- 17530616
TI  - Shock wave therapy reduces necrotic flap zones and induces VEGF expression in
      animal epigastric skin flap model.
AB  - The effect of extracorporeal shock wave (ESW) therapy on skin flap survival and
      growth factor expression was investigated in a rat model using epigastric skin
      flap. Treatment and control groups each contained 20 animals. ESW effectively
      enhanced epigastric skin flap survival by significant reduction of areas of
      necrotic zones. At day 7 after the operation, necrotic zones of 4.2% were found
      in the ESW-treated group compared with 18.3% in the control group ( P < 0.01).
      Concomitantly, in tissue samples adjacent to the necrosis areas, increased
      vascular endothelial growth factor expression was observed in the ESW-treated
      animals (median 84.5%, range 57.4 to 94.5%) compared with the control group
      (median 46.7%, range 29.1 to 93.1%; P < 0.1). However, for expression of basic
      fibroblast growth factor, no difference was found between the two groups. The
      authors conclude that the success of the shock wave treatment may partly be due
      to modulation of growth factor expression.

PMID- 17530617
TI  - Diffusion tensor MRI in rat models of invasive and well-demarcated brain tumors.
AB  - Diffusion tensor imaging (DTI) and its metrics, such as mean diffusivity (MD) and
      fractional anisotropy (FA), have been used to detect the extent of brain tumors
      and understand tumor growth and its influence on the surrounding tissue. However,
      there are conflicting reports on how DTI metrics can be used for tumor diagnosis.
      The physiological interpretation of these metrics in terms of tumor growth is
      also not clear. The objective of this study was to investigate the DTI parameters
      in two rat brain tumor models (9L and F98) with different patterns of
      aggressiveness by longitudinal monitoring of tumor growth and comparing the DTI
      parameters of these two tumor models. In addition to the standard DTI metrics, MD
      and FA, we measured other metrics representing diffusion tensor shape, such as
      linear and planar anisotropy coefficients (CL and CP), and orientational
      coherence measured by lattice index (LI), to characterize the two tumor models.
      The 9L tumor had higher FA, CL, and LI than the F98 tumor. F98 had a larger
      difference in anisotropies between tumor and peritumor regions than 9L. From the
      eigenvalues, it was found that the increase in CL and trace of the 9L tumor was
      due to an increase in the primary eigenvalue, whereas the increase in CP in the
      peritumor region was due to an increase in both primary and secondary eigenvalues
      and a decrease in tertiary eigenvalue. Our results indicate that shape-oriented
      anisotropy measures, such as CL and CP, and orientational coherence measures,
      such as LI, can provide useful information in differentiating these two tumor
      models and also differentiating tumor from peritumoral regions.

PMID- 17530618
TI  - Prostate cancer-specific mortality after radical prostatectomy or external beam
      radiation therapy in men with 1 or more high-risk factors.
AB  - BACKGROUND: Estimates of prostate cancer-specific mortality (PCSM) were
      determined after radical prostatectomy (RP) or radiation therapy (RT) in men with
      >or=1 high-risk factors. METHODS: The study cohort comprised 948 men who
      underwent RP (N = 660) or RT (N = 288) for localized prostate cancer between 1988
      and 2004 and had at least 1 of the following high-risk factors: a prostate
      specific antigen (PSA) velocity >2 ng/mL/year during the year before diagnosis, a
      biopsy Gleason score of >or=7, a PSA level of >or=10 ng/mL, or clinical category
      T2b or high disease. Grays regression was used to evaluate whether the number and
      type of high-risk factors were associated with time to PCSM. RESULTS: Multiple
      determinants of high risk were found to be significantly associated with a
      shorter time to PCSM after RP (P < .001) or RT (P <or= .001). The solitary
      presence of a PSA velocity >2 ng/mL/year was associated with an increased risk of
      PCSM after RP (hazards ratio [HR] of 7.3; 95% confidence interval [95% CI], 1.0
      59 [P = .05]) or RT (HR of 12.1; 95% CI, 1.4-105 [P = .02]) when compared with
      men with any other single high-risk factor. CONCLUSIONS: Men with a PSA velocity
      >2 ng/mL/year had a significantly higher risk of PCSM compared with men who had
      any other single high-risk factor. These men should be considered for randomized
      trials evaluating the impact on PCSM from adding systemic agents to standards of
      care for men with high-risk PC.

PMID- 17530619
TI  - Characteristics of pediatric chemotherapy medication errors in a national error
      reporting database.
AB  - BACKGROUND: Little is known regarding chemotherapy medication errors in
      pediatrics despite studies suggesting high rates of overall pediatric medication
      errors. In this study, the authors examined patterns in pediatric chemotherapy
      errors. METHODS: The authors queried the United States Pharmacopeia MEDMARX
      database, a national, voluntary, Internet-accessible error reporting system, for
      all error reports from 1999 through 2004 that involved chemotherapy medications
      and patients aged <18 years. RESULTS: Of the 310 pediatric chemotherapy error
      reports, 85% reached the patient, and 15.6% required additional patient
      monitoring or therapeutic intervention. Forty-eight percent of errors originated
      in the administering phase of medication delivery, and 30% originated in the drug
      dispensing phase. Of the 387 medications cited, 39.5% were antimetabolites, 14.0%
      were alkylating agents, 9.3% were anthracyclines, and 9.3% were topoisomerase
      inhibitors. The most commonly involved chemotherapeutic agents were methotrexate
      (15.3%), cytarabine (12.1%), and etoposide (8.3%). The most common error types
      were improper dose/quantity (22.9% of 327 cited error types), wrong time (22.6%),
      omission error (14.1%), and wrong administration technique/wrong route (12.2%).
      The most common error causes were performance deficit (41.3% of 547 cited error
      causes), equipment and medication delivery devices (12.4%), communication (8.8%),
      knowledge deficit (6.8%), and written order errors (5.5%). Four of the 5 most
      serious errors occurred at community hospitals. CONCLUSIONS: Pediatric
      chemotherapy errors often reached the patient, potentially were harmful, and
      differed in quality between outpatient and inpatient areas. This study indicated
      which chemotherapeutic agents most often were involved in errors and that
      administering errors were common. Investigation is needed regarding targeted
      medication administration safeguards for these high-risk medications.

PMID- 17530620
TI  - First and second line imatinib treatment in chronic myelogenous leukemia patients
      expressing rare e1a2 or e19a2 BCR-ABL transcripts.
AB  - During the formation of the Philadelphia (Ph) chromosome, in the majority of
      chronic myelogenous leukemia (CML) patients, the chromosome 22 breakpoint is
      located in the major breakpoint cluster region of the BCR gene (M-bcr). Minor and
      micro breakpoint cluster regions (m-bcr with e1a2 transcript and micro-bcr with
      e19a2 transcript) are rarely affected and have been suggested to be associated
      with peculiar CML phenotypes. Despite the different clinical characteristics, it
      is currently not established, whether different therapeutic options are
      preferably recommended for the treatment of e1a2 or e19a2 CML. Here we report two
      patients with e1a2 and one patient with e19a2 translocations, treated with
      different approaches including imatinib. First and second line imatinib
      treatments induced haematologic response in all of the three patients, and major
      cytogenetic response in one patient with e1a2, as well as in the patient with
      e19a2 CML. However, relapse occurred in the patient with e19a2 CML, possibly
      caused by the presence of additional chromosomal abnormalities such as an extra
      Ph chromosome, and loss of chromosome Y. Stem cell transplantation (SCT) therapy
      caused complete haematologic response with molecular remission; however, the
      patient died of infectious complication. We conclude that in patients with rare
      BCR-ABL variants, the effectiveness of imatininb treatment may be influenced by
      the CML stage besides the actual molecular type of the rare transcript. However,
      this conclusion cannot be generalized to larger patient groups with rare BCR-ABL
      variants for which further studies may be needed.

PMID- 17530621
TI  - Diagnosing Alzheimer's disease--non-clinicians and computerised algorithms
      together are as accurate as the best clinical practice.
AB  - BACKGROUND: An accurate diagnosis of Alzheimer's disease and an exclusion of
      other dementias is important in many clinical studies. Obtaining such a clinical
      diagnosis in epidemiological studies and clinical trials that recruit large
      numbers of patients is time consuming. OBJECTIVES: To construct an algorithm
      using a limited number of data points to generate a diagnosis of the commonest
      forms of dementia using information collected by non clinicians. METHODS: We
      constructed a computer algorithm to generate a diagnosis of Alzheimer's disease
      (AD), Dementia with Lewy Bodies (DLB), frontotemporal dementia (FTD), vascular
      dementia or to flag the case as needing a clinical review based on a limited
      number of data points taken from a largely structured interview using widely used
      scales. The diagnosis generated in life by the algorithm in a prospective,
      longitudinal study was compared to definitive diagnosis at post mortem. RESULTS:
      Post mortem diagnosis was available for 43 cases. The positive predictive value
      of the algorithm was greater than 95%. AD was diagnosed by the algorithm and at
      post mortem in 36 of the cases. Two cases with FTD were wrongly diagnosed as
      having AD by the algorithm, five cases were flagged as needing a clinical review
      due to concomitant medical conditions of whom four had AD and one, who had been
      diagnosed clinically as having AD, was diagnosed on post mortem with corticobasal
      degeneration. CONCLUSIONS: A combination of non-clinical researchers, a
      structured interview and a computerised algorithm is as effective at identifying
      AD as highly trained and skilled clinicians.

PMID- 17530622
TI  - A randomized, two-year study of the efficacy of cognitive intervention on elderly
      people: the Donostia Longitudinal Study.
AB  - BACKGROUND: Research on non-pharmacological therapies (cognitive rehabilitation)
      in old age has been very limited, and most has not considered the effect of
      interventions of this type over extended periods of time. OBJECTIVE: To
      investigate a new cognitive therapy in a randomized study with elderly people who
      did not suffer cognitive impairment. METHODS: The efficacy of this therapy was
      evaluated by means of post-hoc analysis of 238 people using biomedical,
      cognitive, behavioural, quality of life (QoL), subjective memory, and affective
      assessments. RESULTS: Scores for learning potential and different types of memory
      (working memory, immediate memory, logic memory) for the treatment group improved
      significantly relative to the untreated controls. CONCLUSIONS: The most
      significant finding in this study was that learning potential continued at
      enhanced levels in trained subjects over an intervention period lasting two
      years, thereby increasing rehabilitation potential and contributing to successful
      ageing.

PMID- 17530623
TI  - Aglycone geniposidic acid, a naturally occurring crosslinking agent, and its
      application for the fixation of collagenous tissues.
AB  - A natural compound, aglycone geniposidic acid (aGSA), originated from the fruits
      of Gardenia jasminoides ELLIS was used for the fixation of collagenous tissues.
      The presumed crosslinking reaction mechanism of collagenous tissues with aGSA was
      inferred by reacting aGSA with a bifunctional amine, 1,6-hexanediamine, using a
      series of (1)H NMR, FT-IR, and UV/Vis spectra analyses. aGSA reacted with 1,6
      hexanediamine by a nucleophilic attack on the olefinic carbon atom at C-2 of
      deoxyloganin aglycone, followed by opening the dihydropyran ring to form
      heterocyclic amine compounds. It is inferred that aGSA may form intramolecular
      and intermolecular crosslinks with a heterocyclic structure within collagen
      fibers in tissues. The degrees of tissue fixation by aGSA at different pH values
      were investigated by examining the fixation indices and denaturation temperatures
      of test samples. It was found that the fixation indices and denaturation
      temperatures of test samples fixed at neutral or basic pH (pH 7.4 or pH 8.5) were
      significantly greater than at acidic pH (pH 4.0). The results obtained in this
      study may be used to elucidate the crosslinking mechanism and optimize the
      fixation process for developing bioprostheses fixed by aGSA.

PMID- 17530625
TI  - Comments on 'Current issues in non-inferiority trials' by Thomas R. Fleming,
      Statistics in Medicine, DOI: 10.1002/sim.2855.

PMID- 17530626
TI  - Cyclodextrin multicomponent complexation and controlled release delivery
      strategies to optimize the oral bioavailability of vinpocetine.
AB  - In the present work, to maintain a suitable blood level of vinpocetine (VP) for a
      long period of time, VP-cyclodextrin-tartaric acid multicomponent complexes were
      prepared and formulated in hydroxypropylmethylcellulose matrix tablets. In vitro
      and in vivo performances of these formulations were investigated over a VP
      immediate release dosage form. Solubility studies were performed to evaluate the
      drug pH solubilization profile and to assess the effect of multicomponent
      complexation on VP solubility. The drug release process was investigated using
      United States Pharmacopeia apparatus 3 and a comparative oral pharmacokinetic
      study was subsequently undertaken in rabbits. Solubility studies denoted the pH
      solubility dependence of VP and solubility improvement attained by complexation.
      Dissolution results showed controlled and almost complete release behavior of VP
      over a 12-h period from complex hydroxypropylmethylcellulose-based formulations.
      A clear difference between the pharmacokinetic patterns of VP immediate release
      and VP complex-based formulations was revealed. The area under the plasma
      concentration-time curve after oral administration of complex-based formulations
      was 2.1-2.9 times higher than that for VP immediate release formulation.
      Furthermore, significant differences found for mean residence time, elimination
      half-life, and elimination rate constant values corroborated prolonged release of
      VP from complex-based formulations. These results suggest that the oral
      bioavailability of VP was significantly improved by both multicomponent
      complexation and controlled release delivery strategies.

PMID- 17530627
TI  - Morphological and endocrine study of the ovarian interstitial tissue of viscacha
      (Lagostomus maximus maximus).
AB  - The morphological and endocrine aspects of the ovarian interstitial tissue of
      adult female viscachas were investigated to establish the probable function and
      the biological significance of this compartment in this rodent. Pregnant and
      nonpregnant adult female viscachas were used. The histological characteristics,
      histochemical properties, and ultrastructural features of the interstitial tissue
      were studied. A morphometric study was carried out to measure the relative area
      of lipid droplets. The progesterone and androstenedione levels in ovarian tissue
      as well as in serum were determined by radioimmunoassay. In this species, the
      histological observations showed an abundant interstitial tissue that contained a
      large amount of lipids. The cholesterol and its esters were present in
      nonpregnant females and were scarce in pregnant animals. The most ultrastructural
      differences were observed at mid-pregnancy. At this stage, the interstitial cells
      showed features that suggested higher steroidogenic activity. Furthermore, during
      mid-pregnancy, the relative area of lipid droplets was smaller. Both progesterone
      and androstenedione levels in ovarian tissue and serum were higher during
      pregnancy. Our results suggest that the interstitial tissue may be storage of
      precursor substances for the steroidogenesis via. These precursors are probably
      used when the endocrine requirements are high, that is, during the pregnancy.
      Thus, this compartment may contribute to the normal gestation of Lagostomus.
      However, the relation between the interstitial tissue and the pregnancy is
      complex, and further studies are needed to clearly establish it.

PMID- 17530629
TI  - Processing and in vitro behavior of hydroxyapatite coatings prepared by
      electrostatic spray assisted vapor deposition method.
AB  - Hydroxyapatite (HA) bioactive coatings are often used to improve bone attachment
      and reduce corrosion of metal prosthesis implants. This paper reports the
      preparation of HA coatings onto titanium substrates using a novel electrostatic
      spray assisted vapor deposition (ESAVD)-based method. The deposited coatings are
      characterized using a combination of Fourier transform infrared spectrometer, X
      ray diffraction, Raman spectroscopy, scanning electron microscopy, and scratch
      test. The results confirm that well-crystallized HA coatings can be produced
      directly via the single-step ESAVD process, without further heat-treatment. The
      in vitro behavior of the as-deposited HA coating in simulated body fluid (SBF) is
      also presented. After 14-day immersion in SBF, the adhesion of the HA coating to
      the substrate increases significantly.

PMID- 17530630
TI  - Synthesis and characterization of in situ chitosan-based hydrogel via grafting of
      carboxyethyl acrylate.
AB  - We developed and characterized a novel in situ chitosan-poly(ethylene oxide)
      (PEO) hydrogel via two steps: 2-carboxyethyl acrylate molecules were grafted to
      the primary amine functional groups in chitosan in the first step and then
      Michael type addition reaction was processed between the grafted acrylate end
      groups and the thiol end groups in the PEO. Grafting of acrylate molecules to the
      amine groups in the deacetylated water soluble chitosan was confirmed by
      observing the new acrylate peaks by the FTIR and NMR spectra of the acrylated
      chitosan samples, as well as changes in relative viscosities of chitosan and
      acrylated chitosan. Formation of the chitosan-PEO hydrogel was visually observed
      with digital images after both gelation and hydration. Rheological analyses of
      the hydrogel formation were performed to detect its gelation time, phase angle
      changes, and visco-elastic properties over frequency and strain percentage. Their
      results indicated that the gelation process was completed within 10 min after
      mixing the precursor liquid solutions. An extent of water swelling, mechanical
      strength against compression and the morphologies of the hydrogel surface and
      cross sections after dehydration process were analyzed by microbalance
      measurement, texture analyzer, and scanning electron microscopy observation,
      respectively. Biological activities of the hydrogels were evaluated by observing
      smooth muscle cell behaviors such as cell adhesion and viability as well as by
      measuring the number of adhered cells on their surfaces.

PMID- 17530631
TI  - Temperature-responsive polymer-gold nanocomposites as intelligent therapeutic
      systems.
AB  - The objective of this study was to synthesize and characterize a thermally
      responsive polymer-metal nanocomposite system comprised of a solid gold
      nanoparticle core and thermally responsive interpenetrating polymer network (IPN)
      shell, which was surface functionalized or PEGylated with a covalently bound
      linear poly(ethylene glycol) chain layer. Gold nanoparticles (50 nm diameter)
      were prepared using standard gold chloride and citrate reduction method. These
      particles were then encapsulated inside of a polyacrylamide (PAAm)/poly(acrylic
      acid) (PAA) IPN shell via an in situ inverse emulsion polymerization. The surface
      of the nanocomposite system was then PEGylated via covalent grafting of a linear
      methoxy-PEG-N-hydroxysuccinimide (M.W. 3400) to the primary amine groups of the
      PAAm network. Scanning and transmission electron microscopy were used to confirm
      the successful synthesis and encapsulation of gold nanoparticles within the IPN
      shell. Dynamic light scattering was used to examine the temperature swelling
      response of the IPN particles. Zeta-potential analysis was used to confirm the
      successful PEGylation of the final nanocomposite system.

PMID- 17530632
TI  - Tissue response in the rat and the mouse to degradable dextran hydrogels.
AB  - Two types of hydroxyethyl-methacrylated dextran (dex-HEMA) hydrogels differing in
      crosslink density were compared for local tissue responses and degradation
      characteristics in mice and rats. Implants (1 mm thick, rat: 10 mm diameter,
      mouse: 6 mm diameter) varying in degree of HEMA substitution (DS5 and DS13,
      meaning 5 or 13 HEMA groups per 100 glucose units of dextran) were subcutaneously
      implanted and tissue responses were evaluated at week 2, 6, and 13 after
      implantation. In the rat after 2 weeks a slight fibrous capsule was formed
      composed of macrophages and fibroblasts sometimes accompanied by a minimal
      infiltrate. Small fragments, surrounded by macrophages and giant cells indicated
      hydrogel degradation. After 13 weeks DS5 implants were resorbed while parts of
      the DS13 implants were still present. In the mouse a moderate to strong capsule
      formation was present at 2 weeks accompanied by inflammatory cells (macrophages
      and polymorphonuclear granulocytes) and debris. Draining lymph node activation
      was observed. Skin ulceration was present irrespective of the type of implant.
      Clear differences in the tissue responses between the rat and mouse were noted,
      as well as between implants of different degree of substitution. Mice showed a
      more pronounced early inflammatory response compared with rats, whereas the
      degradation was more complete in rats than in mice. The differences in histology
      between the hydrogels disappeared over time at 13 weeks after implantation and
      similar responses were noted for both types of hydrogels. Both in mice and rats
      the DS5 hydrogels showed a faster degradation rate than the DS13 hydrogels.

PMID- 17530633
TI  - Fabrication and in vitro drug release of drug-loaded star oligo/poly(DL-lactide)
      microspheres made by novel ultrasonic-dispersion method.
AB  - Cholic acid functionalized star oligo/poly(DL-lactide)s with different molecular
      weights were synthesized through the ring-opening polymerization of DL-lactide
      initiated by cholic acid. On the basis of the specific physicochemical properties
      of the star oligo/poly(DL-lactide)s, submicron sized drug-delivery systems were
      fabricated using a very convenient "ultrasonic dispersion method," which did not
      involve toxic organic solvents. The drug-loaded microspheres had a regular
      spherical shape with a narrow size distribution. The effects of ultrasonic power
      and the molecular weight of polymers on the microsphere fabrication were
      investigated. The in vitro drug release was studied. The release profiles were
      fitted by the classical empirical exponential expression. The fitting result
      indicated that the drug release was controlled by combined degradation and
      diffusion mechanism.

PMID- 17530634
TI  - Poly(butyl methacrylate-co-methacrylic acid) tissue engineering scaffold with pro
      angiogenic potential in vivo.
AB  - A poly(butyl methacrylate-co-methacrylic acid) (BMA-MAA) scaffold was fabricated
      by an in situ polymerization solvent casting/particulate leaching technique. It
      displayed high porosity (85-90%), pore interconnectivity, and a pore size range
      of 100-650 microm. Compression testing of the scaffolds demonstrated a dependence
      of the compressive stiffness on several fabrication variables including the ratio
      of monomer to salt used during the polymerization, the degree of salt fusion, and
      the choice of alternative comonomers to BMA. Subcutaneous implantation of BMA-MAA
      scaffolds in mice revealed an increased level of histological angiogenesis in
      tissue invading the pores of the scaffold compared to a BMA control, consistent
      with the prediction that methacrylic acid (MAA) containing copolymer beads are
      angiogenic in a wound healing context. At postoperative day 21, the capillary
      density in the BMA-MAA scaffolds was 56 +/- 13/mm(2) as compared to 32 +/-
      8/mm(2) for the BMA scaffolds. With further investigation, it is expected that
      this biomaterial capable of eliciting an angiogenic response will have widespread
      application in tissue engineering.

PMID- 17530635
TI  - Modified polycarbonate urethane: synthesis, properties and biological
      investigation in vitro.
AB  - A new polycarbonate urethane (PCU-I) was synthesized from aliphatic monomers,
      i.e. polyhexamethylene carbonate diol and 4,4'-methylene-bis cyclohexane
      diisocyanate, a mixture of low molecular diols, and castor oil (containing mainly
      the triglyceride of 12-hydroxyoleic acid). The second synthesized polymer (PCU
      II) did not contain castor oil. Both PCUs had good tensile strength, i.e. 32.5
      and 27.8 MPa for PCU-I and PCU-II, respectively. Modification by castor oil led
      to a decrease in glass transition temperature (T(g) = -14 degrees C for PCU-I and
      -6 degrees C for PCU-II) and an increase in the softening temperature (135 and
      125 degrees C for PCU-I and PCU-II, respectively). Partial crosslinking of PCU-I
      increased the storage modulus of elasticity and provided better resistance to
      sterilization by ETO and gamma radiation. Both PCUs displayed good stability when
      subjected to sterilization by hydrogen peroxide plasma. Neither PCU caused
      cytotoxic effect in mouse fibroblasts (3T3 Balb C). They also had no toxic
      effects on the morphotic components and did not influence changes in the
      hematologic parameters or plasmatic coagulation system of human blood.

PMID- 17530636
TI  - Low number of regulatory T cells in skin lesions of patients with cutaneous lupus
      erythematosus.
AB  - OBJECTIVE: To define the phenotype and function of CD4+,CD25+ regulatory T cells
      (Treg) in patients with cutaneous lupus erythematosus (CLE), a heterogeneous
      autoimmune disease characterized primarily by inflammatory skin lesions. METHODS:
      The number of Treg in skin specimens obtained from patients with various subtypes
      of CLE was investigated by immunohistochemical analysis, using anti-Foxp3 and
      anti-CD4 monoclonal antibodies. Furthermore, characterization of peripheral blood
      CD4+,CD25+ Treg from normal healthy donors and patients with CLE was carried out
      by flow cytometry, analyzing the expression of Foxp3 and Treg subpopulations. We
      also purified CD4+,CD25(high) Treg obtained from patients with CLE and tested the
      sensitivity of these cells to CD95L-mediated apoptosis. RESULTS: Quantitative
      analysis of CD4+ T cells in skin lesions from patients with CLE revealed that the
      number was similar to that in lesions from patients with other chronic
      inflammatory diseases, but the number of Foxp3+ Treg in CLE was significantly
      reduced. There was no correlation between disease subtype and the frequency of
      Foxp3+ Treg in the skin of patients with CLE. In peripheral blood, no significant
      differences were observed in the number and phenotype of CD4+,CD25+ Treg or in
      the sensitivity to apoptosis of CD4+,CD25(high) Treg derived from patients with
      CLE and those derived from normal healthy donors. CONCLUSION: These data suggest
      that an organ-specific abnormality of Treg in the skin underscores the importance
      of analyzing Treg in the affected tissue. Such a local process might give insight
      into the pathogenic mechanisms of CLE and differs from a global peripheral
      dysfunction as reported for patients with a systemic manifestation of the
      disease.

PMID- 17530637
TI  - Apoptosis-induced acetylation of histones is pathogenic in systemic lupus
      erythematosus.
AB  - OBJECTIVE: In systemic lupus erythematosus (SLE), inadequate removal of apoptotic
      cells may lead to challenge of the immune system with immunogenic self antigens
      that have been modified during apoptosis. We undertook this study to evaluate
      whether apoptosis-induced histone modifications are targets for the immune system
      in SLE. METHODS: The epitope of KM-2, a monoclonal antihistone autoantibody
      derived from a lupus mouse, was mapped by random peptide phage display. The
      reactivity of KM-2 and plasma with (acetylated) histone H4 (H4) peptides and with
      nonapoptotic, apoptotic, and hyperacetylated histones was determined by
      immunofluorescence staining, enzyme-linked immunosorbent assay, and Western
      blotting. RESULTS: KM-2 recognized apoptosis-induced acetylation of H4 at lysines
      8, 12, and 16. The majority of plasma samples from SLE patients and lupus mice
      showed higher reactivity with triacetylated H4 peptide (residues 1-22) and with
      hyperacetylated and apoptotic histones than with nonacetylated H4 peptide and
      normal histones. Importantly, administration of triacetylated H4 peptide to lupus
      prone mice before disease onset accelerated the disease by enhancing mortality
      and aggravating proteinuria, skin lesions, and glomerular IgG deposition, while
      the nonacetylated H4 peptide had no pathogenic effect. The delayed-type
      hypersensitivity response in lupus mice against the triacetylated H4 peptide was
      higher than that against the nonacetylated H4 peptide. Bone marrow-derived
      dendritic cells (DCs) cultured in the presence of hyperacetylated nucleosomes
      showed increased expression/production of CD40, CD86, interleukin-6 (IL-6), and
      tumor necrosis factor alpha compared with DCs cultured in the presence of normal
      nucleosomes. Finally, DCs cultured in the presence of hyperacetylated nucleosomes
      were able to activate syngeneic T cells, because IL-2 production increased.
      CONCLUSION: Apoptosis-induced acetylation of nucleosomes may represent an
      important driving force in the development of lupus.

PMID- 17530638
TI  - Improvement of vascular endothelial function using the oral endothelin receptor
      antagonist bosentan in patients with systemic sclerosis.
AB  - OBJECTIVE: Increased endothelin activity may play a role in the pathogenesis of
      vascular injury, a primary feature of systemic sclerosis (SSc; scleroderma). Our
      goal was to test the hypothesis that treatment with the oral endothelin receptor
      antagonist bosentan might improve vascular endothelial function in SSc patients.
      METHODS: A 4-week, prospective, parallel-group study compared 12 SSc patients who
      did not receive bosentan treatment with 12 patients who did receive treatment
      (125 mg/day) for pulmonary hypertension and/or digital ulcers. There were no
      differences in demographic and clinical characteristics or medications between
      the 2 groups. Baseline endothelial dysfunction was documented by decreased
      brachial artery ultrasound-derived flow-mediated dilation (FMD%; <5.5). Pulse
      wave analysis, venous occlusion plethysmography, and measurement of serum
      vascular markers were performed in parallel. RESULTS: FMD%, the main end point,
      increased significantly from a mean +/- SD of 3.1 +/- 1.3% to 8.4 +/- 2.6% after
      4 weeks of bosentan treatment (P < 0.001, compared with a change from 2.4 +/-
      1.6% to 2.4 +/- 2.2% in control patients). Arterial blood pressure, endothelium
      independent vascular function, augmentation index, peripheral flow reserve, as
      well as circulating intercellular adhesion molecule 1, E-selectin, vascular
      endothelial growth factor, and endothelin 1 were not significantly affected by
      bosentan treatment. In patients continuously treated for 4 months, during which
      the dosage of bosentan remained at 125 mg/day (n = 5) or increased to 250 mg/day
      (n = 5), the 4-week results remained unchanged. CONCLUSION: Small doses of
      bosentan improve endothelial function without affecting hemodynamic parameters or
      endothelial activation-related processes, thus supporting a direct, reversible
      effect of endothelin in SSc-associated vascular injury. A long-term, controlled
      trial to examine the potentially global clinical benefit of endothelin receptor
      blockade in patients with early SSc may be warranted.

PMID- 17530639
TI  - Impairment of endothelial cell differentiation from bone marrow-derived
      mesenchymal stem cells: new insight into the pathogenesis of systemic sclerosis.
AB  - OBJECTIVE: Systemic sclerosis (SSc) is a disorder characterized by vascular
      damage and fibrosis of the skin and internal organs. Despite marked tissue
      hypoxia, there is no evidence of compensatory angiogenesis. The ability of
      mesenchymal stem cells (MSCs) to differentiate into endothelial cells was
      recently demonstrated. The aim of this study was to determine whether impaired
      differentiation of MSCs into endothelial cells in SSc might contribute to disease
      pathogenesis by decreasing endothelial repair. METHODS: MSCs obtained from 7 SSc
      patients and 15 healthy controls were characterized. The number of colony-forming
      unit-fibroblastoid colonies was determined. After culture in endothelial-specific
      medium, the endothelial-like MSC (EL-MSC) phenotype was assessed according to the
      surface expression of vascular endothelial growth factor receptors (VEGFRs).
      Senescence, chemoinvasion, and capillary morphogenesis studies were also
      performed. RESULTS: MSCs from SSc patients displayed the same phenotype and
      clonogenic activity as those from controls. In SSc MSCs, a decreased percentage
      of VEGFR-2+, CXCR4+, VEGFR-2+/CXCR4+ cells and early senescence was detected.
      After culturing, SSc EL-MSCs showed increased expression of VEGFR-1, VEGFR-2, and
      CXCR4, did not express CD31 or annexin V, and showed significantly decreased
      migration after specific stimuli. Moreover, the addition of VEGF and stromal cell
      derived factor 1 to cultured SSc EL-MSCs increased their angiogenic potential
      less than that in controls. CONCLUSION: Our data strongly suggest that
      endothelial repair may be affected in SSc. The possibility that endothelial
      progenitor cells could be used to increase vessel growth in chronic ischemic
      tissues may open up new avenues in the treatment of vascular damage caused by
      SSc.

PMID- 17530640
TI  - Bronchoalveolar lavage cellular profiles in patients with systemic sclerosis
      associated interstitial lung disease are not predictive of disease progression.
AB  - OBJECTIVE: To evaluate the prognostic value of bronchoalveolar lavage (BAL)
      cellular profiles in patients with systemic sclerosis-associated interstitial
      lung disease (SSc-ILD). METHODS: BAL cellularity was examined in relation to
      mortality (n = 141), serial pulmonary function findings (n = 134), and
      "progression-free survival" (n = 134), by proportional hazards analysis. Baseline
      severity was quantified according to the extent of disease on high-resolution
      computed tomography, the diffusing capacity for carbon monoxide, and the presence
      or absence of pulmonary hypertension. Mortality was subclassified into overall
      mortality (during 10 years of followup), early mortality (occurring within 2
      years of presentation), and late mortality (occurring 2-10 years after
      presentation). RESULTS: Overall mortality was associated with neutrophilia on BAL
      (hazard ratio 2.23 [95% confidence interval 1.20-4.14], P = 0.01), but this
      effect was lost when disease severity was taken into account. Early mortality was
      associated with neutrophilia on BAL (hazard ratio 8.40 [95% confidence interval
      1.91-36.95], P = 0.005), independent of disease severity. Late mortality was not
      associated with neutrophilia on BAL. The presence of neutrophilia on BAL was not
      associated with time to decline in pulmonary function or progression-free
      survival. Neither eosinophilia nor lymphocytosis on BAL was associated with
      mortality, rapidity of functional deterioration, or progression-free survival.
      These findings were unaltered when treatment status was taken into account.
      CONCLUSION: BAL findings provide only limited prognostic information in SSc-ILD.
      Neutrophilia on BAL is linked to early mortality, but BAL findings are not linked
      to long-term survival or the rapidity of progression of lung disease. The
      usefulness of BAL to define alveolitis in SSc is questionable.

PMID- 17530641
TI  - Normal circulating serum amyloid P component concentration in systemic sclerosis.
AB  - OBJECTIVE: The observation of reduced circulating concentrations of the
      constitutive plasma pentraxin protein, serum amyloid P component (SAP), in serum
      samples obtained from a small number of patients with systemic sclerosis (SSc)
      has been reported as confirmation of an antifibrotic role of this protein.
      Because neither sustained SAP depletion in humans nor SAP deficiency in mice is
      associated with fibrosis, we sought to establish rigorously the serum SAP
      concentration in well-characterized patients with SSc. METHODS: Serum
      concentrations of SAP were measured by electroimmunoassay in a cross-sectional
      cohort of 20 patients with diffuse cutaneous SSc and 12 patients with limited
      cutaneous SSc, and in a separate 12-month longitudinal cohort of 13 patients with
      diffuse disease and 37 patients with limited disease. The extent and severity of
      disease were characterized in detail at the time of serum sampling. Serum
      concentrations of the classic acute-phase reactants, C-reactive protein and serum
      amyloid A protein, were measured by immunonephelometric assays. RESULTS: SAP
      values were entirely within the normal range, regardless of the extent and
      severity of disease, apart from a very few isolated raised values associated with
      acute intercurrent complications causing major acute-phase responses. CONCLUSION:
      We observed no reduced circulating concentrations of SAP in patients with SSc,
      nor any evidence of an association between SAP levels and the extent or severity
      of fibrosis.

PMID- 17530642
TI  - Comprehensive investigation of disease-specific short peptides in sera from
      patients with systemic sclerosis: complement C3f-des-arginine, detected
      predominantly in systemic sclerosis sera, enhances proliferation of vascular
      endothelial cells.
AB  - OBJECTIVE: To identify pathogenic and/or disease-specific short peptides in sera
      from patients with systemic sclerosis (SSc). METHODS: Serum samples from 40
      patients with SSc, 30 patients with systemic lupus erythematosus, 21 patients
      with rheumatoid arthritis, 30 patients with osteoarthritis, and 26 healthy donors
      were tested. Short peptides with molecular weights of smaller than approximately
      3 kd, purified from the sera by magnetic bead-based hydrophobic interaction
      chromatography 18, were detected and their amino acid sequences determined using
      matrix-assisted laser desorption ionization-time-of-flight mass spectrometry.
      Effects of the identified peptides on fibroblasts and microvascular endothelial
      cells were tested using synthesized peptides and sera containing the peptides.
      RESULTS: A group of peptides with mass/charge (m/z) values of 1,865, 1,778,
      1,691, 1,563, and 1,450 were detected predominantly in the SSc sera. These
      peptides were identified as family members of complement C3f-des-arginine (DRC3f)
      derived from C3b. The level of DRC3f (m/z 1,865) was related to vascular
      involvement in SSc and to SSc disease activity. The synthesized peptides of DRC3f
      and C3f, as well as the filtrated sera containing DRC3f, enhanced proliferation
      of microvascular endothelial cells, but not fibroblasts. Both DRC3f and C3f
      increased production of transforming growth factor beta1 by dermal microvascular
      endothelial cells. CONCLUSION: This comprehensive peptidomics analysis revealed
      the predominance of DRC3f in the sera of patients with SSc. Investigation of
      DRC3f may be a useful tool for the diagnosis and evaluation of disease activity
      in SSc. Moreover, its demonstrated effects on endothelial cells suggest a
      potential role for DRC3f in the pathophysiologic mechanisms of SSc.

PMID- 17530643
TI  - Clinical, immunologic, and genetic features of familial systemic sclerosis.
AB  - OBJECTIVE: To examine whether the affected first-degree relatives within
      multicase systemic sclerosis (SSc; scleroderma) families are concordant for
      autoantibody profile, disease type, and HLA class II haplotypes and whether
      clinical expression and serologic characteristics of familial SSc differ from
      those of sporadic SSc. METHODS: Seven hundred ten SSc families from the
      Scleroderma Family Registry and DNA Repository (Scleroderma Registry) were
      examined, and 18 multicase families were identified. SSc cases and their first
      degree family members underwent serologic testing for different autoantibodies.
      The disease type and various disease features were abstracted from the available
      medical records. Additionally, HLA class II typing was performed on the multicase
      SSc sibpairs. RESULTS: The observed SSc-specific antibody concordance within each
      multicase SSc family was statistically more common than expected by chance alone
      (P = 0.007). The autoantibody profile and disease features of familial and
      sporadic SSc cases did not differ significantly. The frequency of autoantibody
      positivity was not different between unaffected first-degree family members of
      patients from multicase versus singleton SSc families. HLA haplotype sharing
      between SSc sibpairs was significantly more common than expected (P = 0.011).
      CONCLUSION: The affected members within multicase SSc families tend to be
      concordant for SSc-specific autoantibodies and HLA haplotypes; familial SSc does
      not appear to be a unique disease subset.

PMID- 17530644
TI  - Amelioration of pain and histopathologic joint abnormalities in the Col1-IL
      1beta(XAT) mouse model of arthritis by intraarticular induction of mu-opioid
      receptor into the temporomandibular joint.
AB  - OBJECTIVE: To evaluate opioid receptor function as a basis for novel
      antinociceptive therapy in arthritis. METHODS: We induced human mu-opioid
      receptor (HuMOR) expression in arthritic joints of mice, using the feline
      immunodeficiency virus (FIV) vector, which is capable of stably transducing
      dividing, growth-arrested, and terminally differentiated cells. Male and female
      Col1-IL-1beta(XAT)-transgenic mice developed on a C57BL/6J background and wild
      type littermates were studied. RESULTS: A single injection of FIV(HuMOR) into the
      temporomandibular joints of Col1-IL-1beta(XAT)-transgenic mice 1 week prior to
      induction of arthritis prevented the development of orofacial pain and joint
      dysfunction, and reduced the degree of histopathologic abnormality in the joint.
      In addition, FIV(HuMOR) prevented the attendant sensitization of trigeminal
      sensory neurons and activation of astroglia in brainstem trigeminal sensory
      nuclei. These effects were mediated by the transduction of primary sensory
      neurons via transport of FIV vectors from peripheral nerve endings to sensory
      ganglia, as evidenced by HuMOR expression in neuronal cell bodies located in the
      trigeminal ganglia, as well as in their proximal and distal nerve branches
      located in the main sensory and subnucleus caudalis of the brainstem and joints,
      respectively. The presence of MOR ligands predominantly in the descending
      trigeminal nucleus suggested that the observed antinociception occurred at the
      subnucleus caudalis. Articular chondrocytes and meniscal tissue were also
      infected by FIV(HuMOR), which presumably exerted an antiinflammatory effect on
      cartilage. CONCLUSION: Our results indicate that prophylactic therapy with MOR
      overexpression in joints can successfully prevent the development of pain,
      dysfunction, and histopathologic abnormalities in the joints in arthritis. These
      findings may provide a basis for the future development of spatiotemporally
      controlled antinociceptive and antiinflammatory therapy for arthritis.

PMID- 17530645
TI  - Coffee consumption and risk of incident gout in men: a prospective study.
AB  - OBJECTIVE: Coffee is one of the most widely consumed beverages in the world and
      may affect the risk of gout via various mechanisms. We prospectively evaluated
      the relationship between coffee intake and the risk of incident gout in a large
      cohort of men. METHODS: Over a 12-year period, we studied 45,869 men with no
      history of gout at baseline. Intake of coffee, decaffeinated coffee, tea, and
      total caffeine was assessed every 4 years through validated questionnaires. We
      used a supplementary questionnaire to ascertain whether participants met the
      American College of Rheumatology survey criteria for gout. RESULTS: We documented
      757 confirmed incident cases of gout. Increasing coffee intake was inversely
      associated with the risk of gout. The multivariate relative risks (RRs) for
      incident gout according to coffee consumption categories (0, <1, 1-3, 4-5, and >
      or = 6 cups per day) were 1.00, 0.97, 0.92, 0.60 (95% confidence interval [95%
      CI] 0.41-0.87), and 0.41 (95% CI 0.19-0.88), respectively (P for trend = 0.009).
      For decaffeinated coffee, the multivariate RRs according to consumption
      categories (0, <1, 1-3, and > or = 4 cups per day) were 1.00, 0.83, 0.67 (95% CI
      0.54-0.82), and 0.73 (95% CI 0.46-1.17), respectively (P for trend = 0.002).
      Total caffeine from all sources and tea intake were not associated with the risk
      of gout. CONCLUSION: These prospective data suggest that long-term coffee
      consumption is associated with a lower risk of incident gout.

PMID- 17530646
TI  - TNF polymorphisms in psoriasis: association of psoriatic arthritis with the
      promoter polymorphism TNF*-857 independent of the PSORS1 risk allele.
AB  - OBJECTIVE: Single-nucleotide polymorphisms (SNPs) of the tumor necrosis factor
      gene TNF at positions -238 and -308 have been associated with psoriasis vulgaris
      and psoriatic arthritis (PsA). The strong linkage disequilibrium (LD) at
      chromosome region 6p21, a region known to harbor risk factors for psoriasis
      susceptibility (PSORS1) other than just SNPs of the TNF gene, renders the
      interpretation of these findings difficult. The aim of this study was to analyze
      several SNPs of the TNF gene and its neighboring LTA gene for independent and
      dependent carriage of the PSORS1 risk allele. METHODS: SNPs in the promoter of
      the TNF (-238G/A, -308G/A, -857C/T, and -1031T/C), LTA (+252A/G), TNLFRSF1A
      (+36A/G), and TNLFRSF1B (+676T/G) genes were genotyped in 375 psoriasis patients,
      375 PsA patients, and 376 controls. The Trp- Trp-Cys-Cys haplotype of the CCHCR1
      gene (CCHCR1*WWCC) was used as an estimate of the risk allele PSORS1. RESULTS:
      Whereas we were able to confirm the previously described strong association of
      allele TNF*-238A with psoriasis, our study revealed that this association was
      completely dependent on carriage of the PSORS1 risk allele. For PsA, but not
      psoriasis vulgaris without joint involvement, a strong association with the
      allele TNF*-857T (odds ratio 1.956 [95% confidence interval 1.334-2.881];
      corrected P = 0.0025) was also detected in patients negative for the PSORS1 risk
      allele. CONCLUSION: Our results indicate that there are genetic differences
      between psoriasis vulgaris patients with and without joint manifestations. While
      the previously reported association between TNF*-238A and psoriasis seems to
      primarily reflect LD with PSORS1, TNF*-857T may represent a risk factor for PsA
      that is independent of the PSORS1 allele.

PMID- 17530647
TI  - Microscopic polyangiitis presenting as a "pulmonary-muscle" syndrome: is
      subclinical alveolar hemorrhage the mechanism of pulmonary fibrosis?
AB  - Microscopic polyangiitis (MPA) may present with a syndrome that resembles
      idiopathic pulmonary fibrosis (IPF). We describe an MPA patient with the clinical
      presentation of a "pulmonary-muscle" syndrome in which interstitial lung disease
      antedated the onset of myopathy. Identification of vasculitis on muscle biopsy
      was instrumental in recognizing clinical, radiographic, and histopathologic
      features that were more characteristic of MPA than of IPF. Institution of
      glucocorticoid and cyclophosphamide therapy led to the induction of a complete
      remission. The histologic findings in this case implicate subclinical episodes of
      alveolar hemorrhage as the mechanism of interstitial lung disease in MPA.

PMID- 17530648
TI  - Inflammatory rheumatic disease and smoking are predictors of aortic inflammation:
      a controlled study of biopsy specimens obtained at coronary artery surgery.
AB  - OBJECTIVE: Several inflammatory rheumatic diseases are associated with
      accelerated atherosclerosis. Atherosclerosis may result from systemic and/or
      local vascular inflammation. The aim of this study was to evaluate the occurrence
      of chronic inflammatory infiltrates in the aortas of patients with and those
      without inflammatory rheumatic disease who had undergone coronary artery bypass
      graft (CABG) surgery, and to assess the relationship between the infiltrates and
      other factors thought to play a role in atherosclerosis, such as smoking.
      METHODS: Aortic specimens routinely removed during CABG surgery in 66 consecutive
      patients with inflammatory rheumatic disease and 51 control patients without
      inflammatory rheumatic disease were examined by light microscopy for the
      occurrence, location, and severity of chronic inflammatory infiltrates and
      atherosclerotic lesions. RESULTS: Mononuclear cell infiltrates in the inner
      adventitia (apart from those localized along the epicardium) were more frequent
      in the group of patients with inflammatory rheumatic disease (47% versus 20%; P =
      0.002, odds ratio [OR] OR 3.6, 95% confidence interval [95% CI] 1.6-8.5), and the
      extent of these infiltrates was greater. Multivariate analyses revealed that the
      occurrence of mononuclear cell infiltrates was associated with inflammatory
      rheumatic disease (OR 2.99, P = 0.020) and current smoking (OR 3.93, P = 0.012),
      and they were observed in 6 of 7 patients with a history of aortic aneurysm.
      Inflammatory infiltrates in the media were seen only in patients with
      inflammatory rheumatic disease. The frequency of atherosclerotic lesions,
      inflammation within the plaques, and epicardial inflammatory infiltrates in the 2
      groups was equal. CONCLUSION: Among aortic samples collected during CABG surgery,
      those obtained from patients with inflammatory rheumatic disease had more
      pronounced chronic inflammatory infiltration in the media and inner adventitia
      than those obtained from control patients. Current smoking was an independent
      predictor of chronic inner adventitial infiltrates. The infiltrates may represent
      an inflammatory process that promotes atherosclerosis and formation of aneurysms.

PMID- 17530649
TI  - Stepwise formation of patterned cell co-cultures in silicone tubing.
AB  - Here, we describe a method for producing patterned cell adhesion inside silicone
      tubing. A platinum (Pt) needle microelectrode was inserted through the wall of
      the tubing and an oxidizing agent electrochemically generated at the inserted
      electrode. This agent caused local detachment of the anti-biofouling heparin
      layer from the inner surface of the tubing. The cell-adhesive protein fibronectin
      selectively adsorbed onto the newly exposed surface, making it possible to
      initiate a localized cell culture. The electrode could be readily set in place
      without breaking the tubular structure and, importantly, almost no culture
      solution leaked from the electrode insertion site after the electrode was
      removed. Ionic adsorption of poly-L-lysine at the tubular region retaining a
      heparin coating was used to switch the heparin surface from cell-repellent to
      cell-adhesive, thereby facilitating the adhesion of a second cell type. The
      combination of the electrode-based technique with layer-by-layer deposition
      enabled the formation of patterned co-cultures within the semi-closed tubular
      structure. The utility of this approach was demonstrated by patterning co
      cultures of hepatocytes or endothelial cells with fibroblasts. The controlled co
      cultures inside the elastic tubing should be of value for cell-cell interaction
      studies following application of chemical or mechanical stimuli and for tissue
      engineering-based bioreactors.

PMID- 17530650
TI  - Functional defect of circulating regulatory CD4+ T cells in patients with
      Wegener's granulomatosis in remission.
AB  - OBJECTIVE: Accumulating data support the role of regulatory T cells, a subset of
      CD4+ T cells that expresses CD25(high) and the transcription factor forkhead box
      P3 (FoxP3), in controlling and preventing autoimmunity. In Wegener's
      granulomatosis (WG), an autoimmune vasculitis, up-regulation of CD25 on
      circulating CD4+ T cells has been observed, even in patients in remission. The
      objective of this study was to test whether the frequency and/or function of Treg
      cells from WG patients in remission are disturbed. METHODS: Peripheral blood
      mononuclear cells were freshly isolated from 52 WG patients in remission and from
      27 age- and sex-matched healthy control subjects. The proportion of circulating
      Treg cells was assessed by flow cytometry using CD4, CD25, FoxP3, and CD45RO
      markers. Anergy and suppressive function of CD25(high),CD4+ T cells were
      determined using polyclonal stimulants and coculture assay in 10 WG patients in
      remission and in 10 age- and sex-matched healthy controls. RESULTS: In WG
      patients, a significant increase was observed in the percentage of circulating
      CD25(high),CD4+ and CD25(low),CD4+ T cells, whereas CD25-,CD4+ T cells were
      decreased, as compared with healthy controls. Among circulating CD4+ T cells, an
      expanded percentage of Treg cells (CD25(high),FoxP3+) with memory phenotype was
      present in WG patients. However, when the suppressive function of CD25(high),CD4+
      T cells was tested, CD25(high),CD4+ T cells from WG patients showed diminished or
      absent suppression of responder T cell proliferation. The impaired suppression
      was not due to responder cell resistance (as shown by crisscross experiments with
      T cells from healthy controls) or altered survival of Treg cells. CONCLUSION:
      These data indicate that WG patients in remission have an expanded proportion of
      Treg cells that are functionally defective. This observation may be relevant to
      the development and relapsing course of this autoimmune vasculitis.

PMID- 17530651
TI  - Prevalence of adult systemic lupus erythematosus in California and Pennsylvania
      in 2000: estimates obtained using hospitalization data.

PMID- 17530652
TI  - Risk of interstitial lung disease associated with leflunomide treatment in Korean
      patients with rheumatoid arthritis.

PMID- 17530653
TI  - Mannose-binding lectin and agalactosyl IgG and risk of ischemic heart disease in
      rheumatoid arthritis: comment on the article by Troelsen et al.

PMID- 17530655
TI  - Corticosteroids in preventing severe lupus flares: do all patients have the same
      risk? Comment on the article by Tseng et al.

PMID- 17530657
TI  - Treatment of patients with neonatal-onset multisystem inflammatory
      disease/chronic infantile neurologic, cutaneous, articular syndrome: comment on
      the article by Matsubara et al.

PMID- 17530659
TI  - Identification of transition from primary Raynaud's phenomenon to secondary
      Raynaud's phenomenon by nailfold videocapillaroscopy: comment on the article by
      Hirschl et al.

PMID- 17530661
TI  - Moving forward with quality: pay for reporting meets rheumatology.

PMID- 17530662
TI  - The effective use of questionnaires in clinical practice.

PMID- 17530663
TI  - Assessment of American College of Rheumatology quality criteria for rheumatoid
      arthritis in a pre-quality criteria patient cohort.
AB  - OBJECTIVE: To evaluate the American College of Rheumatology (ACR) starter set of
      quality measures for rheumatoid arthritis (RA) in an actual patient cohort that
      preceded publication of the quality measures. METHODS: We retrospectively applied
      the 2006 ACR quality criteria to a prospectively studied cohort of 568 patients
      with RA treated by 1,932 unique physicians including 255 different
      rheumatologists between the years 1999 and 2003. Data on performance were
      obtained from self-report surveys and medical record review within 12 months.
      RESULTS: At least 1 joint examination was performed in 98% of patients. Patient
      and physician global assessments were reported for 79% and 74% of patients,
      respectively. A total of 85% of patients received disease-modifying antirheumatic
      drugs (DMARDs). DMARD adjustments were made for 50% of patients in whom
      increasing disease activity was noted at least once and for 64% of patients in
      whom increasing disease activity was noted during 2 (of 4) 3-month periods within
      the year. Compared with self-report surveys, medical records substantially
      underreported performance on quality measures. CONCLUSION: The ACR-endorsed
      quality measures for RA can be assessed using available data sources. When both
      self-report and medical record data are used, adherence rates, designed to serve
      as minimum standards of care, were moderate or high for most measures. Prior to
      using indicators to compare quality across groups, specific strategies for
      operationalizing measures and for using accurate data sources to assess adherence
      to the measures should be defined.

PMID- 17530664
TI  - The polymyalgia rheumatica activity score in daily use: proposal for a definition
      of remission.
AB  - OBJECTIVE: To confirm the reliability and applicability of the Polymyalgia
      Rheumatica Disease Activity Score (PMR-AS), and to establish a threshold for
      remission. METHODS: First, 78 patients with PMR (50 women/28 men, mean age 65.97
      years) were enrolled in a cross-sectional evaluation. The PMR-AS, patient's
      satisfaction with disease status (PATSAT; range 1-5), erythrocyte sedimentation
      rate (ESR; first hour), and a visual analog scale of patients' general health
      assessment (VAS patient global; range 0-100) were recorded. Subsequently, another
      39 PMR patients (24 women/15 men, mean age 68.12 years) were followed
      longitudinally. Relationships between the PMR-AS, PATSAT, ESR, and VAS patient
      global were analyzed by the Kruskal-Wallis test, Spearman's rank correlation, and
      kappa statistics. PMR-AS values in patients with a PATSAT score of 1 and a VAS
      patient global <10 formed the basis to establish a remission threshold. RESULTS:
      PMR-AS values were significantly related to PATSAT (P < 0.001), VAS patient
      global (P < 0.001), and ESR (P < 0.01). PATSAT and VAS patient global were
      reasonably different (kappa = 0.226). The median PMR-AS score in patients with
      PATSAT score 1 and VAS patient global <10 was 0.7 (range 0-3.3), and the
      respective 75th percentile was 1.3. To enhance applicability, a range from 0 to
      1.5 was proposed to define remission in PMR. The median ESR in these patients was
      10 mm/hour (range 3-28), indicating external validity. CONCLUSION: We
      demonstrated the reliability, validity, and applicability of the PMR-AS in daily
      routine. Moreover, we proposed a remission threshold (0-1.5) founded on patient
      dependent parameters.

PMID- 17530665
TI  - The novel correlation of carbonic anhydrase II and anion exchanger 1 in gills of
      the spotted green pufferfish, Tetraodon nigrovirids.
AB  - A novel relationship between branchial carbonic anhydrase II (CAII) and anion
      exchanger 1 (AE1) was investigated in the euryhaline spotted green pufferfish
      (Tetraodon nigroviridis). The immunoblots revealed that AE1 was only detected in
      the membrane fraction of gills while CAII can be probed both in the membrane and
      cytosol fractions of gills. CAII protein abundance in the membrane fraction is
      salinity dependent. Immunological detection of the membrane fraction CAII protein
      in gills showed 3.9-fold higher in the hyposmotic (freshwater) group than the
      hyperosmotic (seawater;35 per thousand) group. In contrast, there was no change
      in the protein level of cytosolic CAII between seawater and freshwater groups.
      The whole-mount immunocytochemical staining demonstrated that both AE1 and CAII
      were colocalized to the Na(+)/K(+)-ATPase-immunoreactive cells in gill epithelium
      of the pufferfish. The interaction between CAII and AE1 was further identified by
      co-immunoprecipitation because AE1 was detected in the immunoprecipitates of CAII
      and vice versa. Our results showed that in pufferfish gills CAII was not only
      expressed in the cytosol to produce the substrate for AE1 transport during Cl(-)
      influx but also associated with the plasma membrane via AE1. Obviously, it is
      essential for the physiological function of AE1 to interact with CAII in the
      membrane of gill Na(+)/K(+)-ATPase-immunoreactive cells. To our knowledge, this
      is the first study to demonstrate the interaction of branchial CAII and AE1 in
      fish. The novel correlation proposed a new model of Cl(-)/HCO(3) (-) transport in
      gills of the teleosts.

PMID- 17530666
TI  - Clinical trials in restless legs syndrome--recommendations of the European RLS
      Study Group (EURLSSG).
AB  - The European Restless Legs Syndrome (RLS) Study Group (EURLSSG) is an association
      of European RLS experts who are actively involved in RLS research. A major aim of
      the Study Group is the development and continuous improvement of standards for
      diagnosis and treatment of RLS. Several members developed study designs and
      evaluation methods in investigator-initiated trials early in the 1990s, and all
      members have since contributed to many pivotal and nonpivotal drug trials for the
      treatment of RLS. The recommendations on clinical investigations of
      pharmacological treatment of RLS patients summarize the group's expertise and
      knowledge acquired through clinical trials. The recommendations primarily address
      how to plan and conduct confirmatory, randomized clinical studies in patients
      with idiopathic RLS. Advice is presented for the diagnosis of RLS and clinical
      and polysomnographic inclusion and exclusion criteria. Primary and secondary
      endpoints for an evaluation of efficacy are based on a critical description of
      validated methods for both short- and long-term trials, also in special
      populations (children, pregnant women, elderly patients). The recommendations
      include the assessment of augmentation. Finally, general issues including the
      evaluation of safety and tolerability, as well as specific neurological and
      cardiovascular risks and sleep attacks/daytime somnolence, are discussed. The aim
      of these recommendations is to support research groups or pharmaceutical
      companies in the design of optimized study protocols.

PMID- 17530667
TI  - A simple carbon isotope model for reconstructing prehistoric human diet.
AB  - A compilation of experimental animal data shows that neither delta13C(collagen)
      nor delta13C(apatite) nor Delta13C(CO-AP) indicate diagnostic reconstructions of
      diet, diet energy and diet protein. In contrast, plots of delta13C(collagen)
      against delta13C(apatite) provide a model of three regression lines (C3, C4, and
      marine diet protein) where position on each line indicates the energy source (C3,
      C4, or mixed). Neither body size nor trophic position appears to affect these
      relationships. Modern free-ranging, terrestrial fauna do not fit the model
      perhaps because they, unlike the experimental fauna, mainly use fermentation
      rather than digestion during energy metabolism. Archaeological humans fall as
      expected based on associated floral and faunal evidence. Foraging people plot at
      positions expected from associated C3 fauna and plants. Those from Cahokia plot,
      as expected, from associated deer, nuts, and maize whereas people from nearby
      smaller sites plot in positions consistent with eating more fish. Agriculturists
      from Ontario and Grasshopper Pueblo plot consistent with dependence on fish by
      the former and on turkeys by the latter. In Tierra del Fuego, people from
      interior regions ate more terrestrial fauna, as suggested by ethnohistoric
      reports, than did people from the coast. In the Southwestern Cape in South Africa
      individuals late in the sequence have pure C3 diets whereas ones early in the
      sequence ate marine protein as suggested by independent archaeological evidence.
      People on San Nicolas Island depended on C4 plants in contrast to other islands
      off California's coast. This simple model provides more detailed and precise
      dietary information than do individual isotopic measures.

PMID- 17530668
TI  - The predictive ability of serum alpha-fetoprotein for hepatocellular carcinoma is
      linked with the characteristics of the target population at surveillance.
AB  - BACKGROUND: Serum alpha-fetoprotein (AFP) is the most important tumor marker for
      hepatocellular carcinoma (HCC). The reported predictive accuracy of AFP for HCC
      widely varied. This study investigated the factors contributory to the
      heterogeneity of the ability of AFP to detect HCC. METHODS: A total of 1,135
      patients were categorized into four groups: HCC undergoing surgical resection (n
      = 248), chronic hepatitis B (CHB, n = 413), chronic hepatitis C (CHC, n = 207),
      and liver cirrhosis (LC, n = 267). The area under the receiver operating
      characteristic curve (AUC) was estimated in different combinations. RESULTS: The
      AUC was the highest when HCC patients were co-analyzed with patients with LC
      (0.805), followed by co-analyzing patients with CHB (0.797) and CHC (0.740). The
      optimal cutoffs for AFP were between 26 and 32 ng/ml. Patients with tumor size
      </=3 cm had a lower positive predictive value (PPV, 30%) compared to patients
      with tumor size >3 cm (46%), and HBsAg-negative and anti-HCV-positive patients
      had the lowest PPV (38%) compared to other groups (60%, 100%, and 82%) at a
      cutoff at 20 ng/ml. The AUC was lower for hepatitis B-negative subjects (0.684
      and 0.509), compared to hepatitis B-positive subjects (0.826 and 0.806)
      stratified by the status of HCV. Elevated ALT >80 U/L and HCC independently
      predicted increased (>20 ng/ml) AFP levels. CONCLUSIONS: Serum AFP had a fairly
      stable predictive accuracy for HCC, with an optimal cutoff around 30 ng/ml. ALT
      level, viral status, and tumor size may significantly confound its ability to
      detect HCC.

PMID- 17530669
TI  - Measuring disease activity and functionality during pregnancy in patients with
      rheumatoid arthritis.
AB  - OBJECTIVE: Pregnancy has a favorable effect on the course of rheumatoid arthritis
      (RA), although the magnitude of this effect is equivocal because RA assessment
      tools have never been validated in pregnancy. The goal of this study was to
      assess how pregnancy influences the scoring of the Disease Activity Score in 28
      joints (DAS28) and the Health Assessment Questionnaire (HAQ), and how both scores
      perform in pregnant patients with RA. METHODS: Thirty-two healthy women and 30
      pregnant patients with RA were prospectively studied during pregnancy and at
      postpartum. At each trimester and postpartum the components of the DAS28 (global
      health [GH], erythrocyte sedimentation rate [ESR], and C-reactive protein level
      [CRP]) and HAQ scores were determined. Maximal influences of healthy pregnancy on
      each component of the DAS28 were calculated. The performances of different DAS28
      scores and the HAQ were also determined in RA patients. Furthermore, variants of
      the HAQ were developed within the HAQ scoring rules. RESULTS: The components of
      the DAS28 were influenced by healthy pregnancy, with average increases in DAS28
      score of 0.22 (GH), 1.1 (ESR), and 0.25 (CRP). The DAS28 calculated with CRP
      (DAS28-CRP) and without GH performed the best in pregnant RA patients. In healthy
      pregnancy, the median HAQ increased to 0.50 in the third trimester and was
      reduced by the HAQ variants to 0.25. CONCLUSION: Pregnancy considerably
      influences the scoring of the DAS28 and HAQ. RA disease activity in pregnant
      patients should preferably be calculated with DAS28-CRP without GH. Even with HAQ
      variants, influences of pregnancy on the assessment of functionality cannot be
      precluded.

PMID- 17530670
TI  - Using Rasch analysis to compare the psychometric properties of the Short Form 36
      physical function score and the Health Assessment Questionnaire disability index
      in patients with psoriatic arthritis and rheumatoid arthritis.
AB  - OBJECTIVE: Item-response theory is increasingly used in the development of robust
      measurement tools. The extent to which the Health Assessment Questionnaire (HAQ)
      disability index (DI) and Short Form 36 (SF-36) physical functioning subscale
      (PF) fit a Rasch model in psoriatic arthritis (PsA) is uncertain. Our objective
      was to compare the psychometric properties of the HAQ DI and SF-36 PF in PsA and
      rheumatoid arthritis (RA) using Rasch analysis. METHODS: Patients with RA (n =
      142) and PsA (n = 134) were identified from a disease register based at a
      regional rheumatology service that serves a population of approximately 400,000
      individuals. Responses to the HAQ DI and SF-36 PF were analyzed for item fit,
      differential item functioning (DIF), scale length (item separation), floor
      effects, and item difficulty by fitting the data to a Rasch model. The extent to
      which each instrument measured the same concept (disability) was also assessed in
      the PsA cohort using the Rasch model. RESULTS: Item separation was much better
      for the SF-36 PF than the HAQ DI in PsA (9.12 logits versus 2.06 logits). There
      was evidence of marked DIF for the HAQ DI items activities, grip, and rising and
      relatively minor DIF for 4 items of the SF-36 PF. The distribution of SF-36 PF
      was better than HAQ DI in PsA, with floor effects of 3.1% versus 30.4%. Common
      person equating demonstrated that the 2 instruments measure the same construct in
      PsA. CONCLUSION: The SF-36 PF has significant psychometric advantages over the
      HAQ DI in PsA.

PMID- 17530671
TI  - Use of accommodations for valued life activities: prevalence and effects on
      disability scores.
AB  - OBJECTIVE: To describe the prevalence of using 4 specific behavioral
      accommodations (assistive devices, personal assistance, limits on the amount or
      kind of activities, and taking more time to perform activities) in the
      performance of valued life activities (VLAs), and to examine the impact of
      accounting for these accommodations on VLA disability scores. METHODS: Data were
      from a panel study of 467 individuals with rheumatoid arthritis (RA) interviewed
      annually by telephone. VLA disability was assessed using a 29-item scale, rating
      difficulty performing each activity and asking whether the 4 types of
      accommodations were used. An unadjusted difficulty score based solely on
      difficulty ratings was calculated, as well as 3 adjusted scores accounting for
      use of assistance or devices, use of assistance, devices, or limitations in
      activities, and use of all 4 accommodations. RESULTS: Accommodations were widely
      used by individuals with RA to perform daily activities. Limits and more time
      were used for more activities than assistance and devices. Adjustment for
      accommodations produced substantial increases in disability scores (e.g., the
      mean total VLA difficulty score increased by 84% after adjustment for all 4
      accommodations). CONCLUSION: The accommodations included on the Health Assessment
      Questionnaire, the most commonly used measure of functioning for RA, include only
      assistive devices and personal assistance, which were not the accommodations most
      frequently used in our sample. If assessments are intended to estimate total
      disease burden, they should include use of a broader range of accommodations to
      develop a more complete picture of how daily function is affected.

PMID- 17530672
TI  - Arthritis symptoms, the work environment, and the future: measuring perceived job
      strain among employed persons with arthritis.
AB  - OBJECTIVE: To develop a measure of job strain related to differing aspects of
      working with arthritis and to examine the demographic, illness, work context, and
      psychosocial variables associated with it. METHODS: Study participants were 292
      employed individuals with osteoarthritis or inflammatory arthritis. Participants
      were from wave 3 of a 4-wave longitudinal study examining coping and adaptation
      efforts used to remain employed. Participants completed an interview-administered
      structured questionnaire, including a Chronic Illness Job Strain Scale (CIJSS)
      and questions on demographic (e.g., age, sex), illness and disability (e.g.,
      disease type, pain, activity limitations), work context (e.g., job type, job
      control), and psychosocial variables (e.g., arthritis-work spillover,
      coworker/managerial support, job perceptions). Principal component analysis and
      multiple linear regression were used to analyze the data. RESULTS: A single
      factor solution emerged for the CIJSS. The scale had an internal reliability of
      0.95. Greater job strain was reported for future uncertainty, balancing multiple
      roles, and difficulties accepting the disease than for current workplace
      conditions. Participants with inflammatory arthritis, more frequent severe pain,
      greater workplace activity limitations, fewer hours of work, less coworker
      support, and greater arthritis-work spillover reported greater job strain.
      CONCLUSION: The findings underscore the diverse areas that contribute to
      perceptions of job strain and suggest that existing models of job strain do not
      adequately capture the stress experienced by individuals working with chronic
      illnesses or the factors associated with job strain. Measures similar to the
      CIJSS can enhance the tools researchers and clinicians have available to examine
      the impact of arthritis in individuals' lives.

PMID- 17530673
TI  - Do proton-pump inhibitors confer additional gastrointestinal protection in
      patients given celecoxib?
AB  - OBJECTIVE: Celecoxib has a superior upper-gastrointestinal (GI) safety profile
      compared with nonselective nonsteroidal antiinflammatory drugs (NS-NSAIDs). It is
      unclear whether the utilization of a proton-pump inhibitor (PPI) with celecoxib
      confers additional protection in elderly patients. We assessed the association
      between GI hospitalizations and use of celecoxib with a PPI versus celecoxib
      alone, and NS-NSAIDs with a PPI or NS-NSAIDs alone in elderly patients. METHODS:
      We conducted a population-based retrospective cohort study using the government
      of Quebec health services administrative databases. Elderly patients were
      included at their first dispensing date for celecoxib or an NS-NSAID between
      April 1999 and December 2002. Prescriptions were separated into 4 groups:
      celecoxib, celecoxib plus PPI, NS-NSAIDs, and NS-NSAIDs plus PPI. Cox regression
      models with time-dependent exposure were used to compare the hazard rates of GI
      hospitalization between the 4 groups adjusting for patient characteristics at
      baseline. RESULTS: There were 1,161,508 prescriptions for celecoxib, 360,799 for
      celecoxib plus PPI, 715,176 for NS-NSAIDs, and 148,470 for NS-NSAIDs plus PPI.
      The adjusted hazard ratios (HRs; 95% confidence intervals [95% CIs]) were 0.69
      (0.52-0.93) for celecoxib plus PPI versus celecoxib, 0.98 (0.67-1.45) for NS
      NSAIDs plus PPI versus celecoxib, and 2.18 (1.82-2.61) for NS-NSAIDs versus
      celecoxib. Subgroup analyses showed that use of a PPI with celecoxib may be
      beneficial in patients ages >/=75 years but was not better than celecoxib alone
      among those ages 66-74 years (HR 0.98, 95% CI 0.63-1.52). CONCLUSION: Addition of
      a PPI to celecoxib conferred extra protection for patients ages >/=75 years. PPI
      did not seem necessary with celecoxib for patients ages 66-74 years.

PMID- 17530674
TI  - Risk of tuberculosis in patients treated with tumor necrosis factor antagonists
      due to incomplete prevention of reactivation of latent infection.
AB  - OBJECTIVE: To evaluate the causes of new cases of active tuberculosis (ATB) in
      patients treated with tumor necrosis factor (TNF) antagonists included in the
      national registry BIOBADASER (Base de Datos de Productos Biologicos de la
      Sociedad Espanola de Reumatologia) after the dissemination of recommendations to
      prevent reactivation of latent tuberculosis infection (LTBI). METHODS: Incidence
      rate of ATB per 100,000 patient-years and 95% confidence intervals (95% CIs) were
      calculated in patients entering BIOBADASER after March 2002 and were stratified
      by compliance with recommendations (complete or incomplete). ATB rates in
      BIOBADASER were compared with the background rate and the rate in the rheumatoid
      arthritis cohort EMECAR (Estudio de la Morbilidad y Expresion Clinica de la
      Artritis Reumatoide) not treated with TNF antagonists. In addition, rates of ATB
      among patients treated with adalimumab, etanercept, and infliximab were estimated
      and compared only for treatments started after September 2003, when all 3 drugs
      became fully available. RESULTS: Following March 2002, a total of 5,198 patients
      treated with a TNF antagonist were registered in BIOBADASER. Fifteen ATB cases
      were noted (rate 172 per 100,000 patient-years, 95% CI 103-285). Recommendations
      were fully followed in 2,655 treatments. The probability of developing ATB was 7
      times higher when recommendations were not followed (incidence rate ratio 7.09,
      95% CI 1.60-64.69). Two-step tuberculosis skin test for LTBI was the major
      failure in complying with recommendations. CONCLUSION: New cases of ATB still
      occur in patients treated with all available TNF antagonists due to lack of
      compliance with recommendations to prevent reactivation of LTBI. Continuous
      evaluation of recommendations is required to improve clinical practice.

PMID- 17530675
TI  - Long-term treatment with methotrexate or tumor necrosis factor alpha inhibitors
      does not increase epstein-barr virus load in patients with rheumatoid arthritis.
AB  - OBJECTIVE: We previously demonstrated that patients with rheumatoid arthritis
      (RA) have a 10-fold systemic Epstein-Barr virus (EBV) overload, very similar to
      that observed in healthy organ transplant recipients. Our objective was to
      monitor EBV load over time in patients with RA receiving methotrexate,
      infliximab, or etanercept to detect possible immunosuppression-associated EBV
      dysregulation, as described in posttransplant lymphoproliferative disease.
      METHODS: The EBV load in the peripheral blood mononuclear cells (PBMCs) from 19
      patients receiving methotrexate, 68 patients receiving infliximab, and 48
      patients receiving etanercept was monitored for durations ranging from 6 months
      to 5 years using a real-time polymerase chain reaction assay previously developed
      for that purpose. The effect of treatment duration on EBV load and the link
      between the Disease Activity Score in 28 joints and EBV load were analyzed by
      generalized estimating equations. RESULTS: Methotrexate tended to decrease EBV
      load over time, but this did not reach significance. Tumor necrosis factor alpha
      (TNFalpha) inhibitors did not significantly modify EBV load over time. Finally,
      high disease activity was significantly associated with high EBV load.
      CONCLUSION: Long-term usage of methotrexate or TNFalpha inhibitors in patients
      with RA does not significantly influence EBV load in PBMCs.

PMID- 17530676
TI  - Benefits of intensive resistance training in patients with chronic polymyositis
      or dermatomyositis.
AB  - OBJECTIVE: To investigate the benefits and safety of an intensive muscular
      training program in patients with chronic polymyositis (PM) and dermatomyositis
      (DM). METHODS: Nine patients with chronic PM or DM (median age 53 years, range 44
      61) were included. Assessments of impairment (10-15 voluntary repetition maximum
      [VRM], the Functional Index 2 [FI-2], the Grippit, and pain rated on the Borg CR
      10 scale), activity limitation (Myositis Activities Profile), and participation
      restriction (patients' disease impact on well-being) were performed 4 weeks prior
      to baseline, at baseline, and after 7 weeks of exercise. A 6-item core set of
      disease activity measures was administered and muscle biopsy samples of vastus
      lateralis were obtained at baseline and after 7 weeks of exercise. Response
      criteria at an individual level were set for disability and disease activity. The
      patients exercised 3 days per week for 7 weeks on loads allowing 10 VRM. RESULTS:
      On a group level there were no significant differences between assessments at 4
      weeks before baseline compared with baseline. The group improved significantly
      regarding 10-15 VRM and FI-2 at 7 weeks compared with baseline (P < 0.05). All
      patients were responders with respect to impairment and 2 were activity
      limitation responders whereas participation restriction remained unchanged in
      all. Two patients were responders with reduced disease activity and no patient
      had signs of increased muscle inflammation in the muscle biopsy sample after 7
      weeks of exercise. CONCLUSION: Patients with chronic, stable PM and DM can
      perform this intensive resistive exercise program with beneficial effects on
      impairment and activity limitation without increased muscle inflammation.

PMID- 17530677
TI  - Cost-utility analysis of a multidisciplinary job retention vocational
      rehabilitation program in patients with chronic arthritis at risk of job loss.
AB  - OBJECTIVE: To estimate from a societal perspective the cost-utility of a
      multidisciplinary job retention vocational rehabilitation program compared with
      usual care in patients with chronic rheumatic diseases at risk of job loss.
      METHODS: Patients (n = 121) were randomly assigned to either the vocational
      rehabilitation program or usual outpatient care initiated by the treating
      rheumatologist. Followup lasted for 2 years. Program costs were estimated using
      time registrations and other societal costs using quarterly cost questionnaires
      filled out by the patients. To estimate quality-adjusted life years, utility was
      assessed using the EuroQol classification system, EuroQol rating scale, Short
      Form 6D, and Time Trade-Off. RESULTS: As part of the vocational rehabilitation
      program, patients on average had a total of 7.1 consultations and the total time
      spent by the multidisciplinary team was 12.7 hours per patient. Program costs
      were estimated at euro1,426, of which approximately 20% were time and travel
      costs incurred by the patients. No significant differences were found in other
      health care consumption, productivity, or quality-adjusted life years. Program
      costs were outweighed by total savings on other health care and nonhealth care
      costs, but not significantly. CONCLUSION: From a societal perspective, it remains
      unclear whether the program reduces or increases total costs. Further research on
      effective vocational rehabilitation is warranted, with special attention to early
      detection of work problems and the collaboration between health care and
      vocational rehabilitation services.

PMID- 17530678
TI  - Joint proprioception, muscle strength, and functional ability in patients with
      osteoarthritis of the knee.
AB  - OBJECTIVE: To test the hypotheses that poor knee joint proprioception is related
      to limitations in functional ability, and poor proprioception aggravates the
      impact of muscle weakness on limitations in functional ability in osteoarthritis
      (OA) of the knee. METHODS: Sixty-three patients with symptomatic OA of the knee
      were tested. Proprioceptive acuity was assessed by establishing the joint motion
      detection threshold (JMDT) in the anteroposterior direction. Muscle strength was
      measured using a computer-driven isokinetic dynamometer. Functional ability was
      assessed by the 100-meter walking test, the Get Up and Go (GUG) test, and the
      Western Ontario and McMaster Universities Osteoarthritis Index physical function
      (WOMAC-PF) questionnaire. Correlation analyses were performed to assess the
      relationship between proprioception, muscle strength, and functional ability.
      Regression analyses were performed to assess the impact of proprioception on the
      relationship between muscle strength and functional ability. RESULTS: Poor
      proprioception (high JMDT) was related to more limitation in functional ability
      (walking time r = 0.30, P < 0.05; GUG time r = 0.30, P < 0.05; WOMAC-PF r = 0.26,
      P <0.05). In regression analyses, the interaction between proprioception and
      muscle strength was significantly related to functional ability (walking time, P
      < 0.001 and GUG time, P < 0.001) but not to WOMAC-PF score (P = 0.625). In
      patients with poor proprioception, reduction of muscle strength was associated
      with more severe deterioration of functional ability than in patients with
      accurate proprioception. CONCLUSION: Patients with poor proprioception show more
      limitation in functional ability, but this relationship is rather weak. In
      patients with poor proprioception, muscle weakness has a stronger impact on
      limitations in functional ability than in patients with accurate proprioception.

PMID- 17530679
TI  - Estimating the probability of radiographic osteoarthritis in the older patient
      with knee pain.
AB  - OBJECTIVE: To determine whether clinical information can practically rule in or
      rule out the presence of radiographic osteoarthritis in older adults with knee
      pain. METHODS: We conducted a cross-sectional diagnostic study involving 695
      adults ages >/=50 years reporting knee pain within the last year identified by
      postal survey and attending a research clinic. Potential indicators of
      radiographic osteoarthritis were gathered by self-complete questionnaires,
      clinical interview, and physical examination. Participants underwent plain
      radiography (posteroanterior, skyline, and lateral views). Radiographic
      osteoarthritis was defined as the presence of definite osteophytes in at least 1
      joint compartment of the index knee. RESULTS: Independent predictors of
      radiographic osteoarthritis were age, sex, body mass index, absence of whole leg
      pain, traumatic onset, difficulty descending stairs, palpable effusion, fixed
      flexion deformity, restricted-flexion range of motion, and crepitus. Using this
      model, 245 participants had a predicted probability >/=80% (practical rule in),
      of whom 231 (94%) actually had radiographic osteoarthritis (specificity 93%).
      Twenty-one participants had a predicted probability <20% (practical rule out), of
      whom only 2 (10%) had radiographic osteoarthritis (sensitivity 99.6%). The
      predicted probability of radiographic osteoarthritis for the remaining 429
      participants fell into an intermediate category (20-79%). CONCLUSION: Simple
      clinical information can be used to estimate the probability of radiographic
      osteoarthritis in individual patients. However, for the majority of community
      dwelling older adults with knee pain this method enables the presence of
      radiographic osteoarthritis to be neither confidently ruled in nor ruled out.
      Prospective validation and updating of these findings in an independent sample is
      required.

PMID- 17530680
TI  - Clinical outcomes, quality of life, and diagnostic uncertainty in the first year
      of polymyalgia rheumatica.
AB  - OBJECTIVE: To evaluate the impact of polymyalgia rheumatica (PMR) on clinical
      outcomes and quality of life (QOL); the relationship between laboratory measures
      and clinical outcomes, and changes in QOL; and agreement between rheumatologists
      in confirming the initial diagnosis. METHODS: We conducted a prospective study of
      129 participants in 8 hospitals in England who met a modified version of the
      Jones and Hazleman criteria and had not started steroid therapy. The main outcome
      measures were response to steroids after 3 weeks (minimum 50% improvement in
      proximal pain, morning stiffness <30 minutes, acute-phase response not elevated),
      relapses, QOL as measured by the Short Form 36 and Health Assessment
      Questionnaire, and diagnosis reassessment at 1 year. RESULTS: At 3 weeks, 55% of
      participants failed to meet our definition of a complete response to steroid
      therapy. Both physical and mental QOL at presentation were substantially lower
      than general population norms and improved by 12.6 (95% confidence interval [95%
      CI] 10.8, 14.4) and 11.2 (95% CI 8.5, 13.8) points, respectively, at 1 year.
      Proximal pain and longer morning stiffness were significantly associated with
      lower physical QOL during followup, whereas erythrocyte sedimentation rate was
      most strongly associated with lower mental QOL during followup. There was
      moderate agreement between clinicians in confirming the PMR diagnosis (kappa
      coefficients 0.49-0.65). CONCLUSION: PMR is a heterogeneous disease with a major
      impact on QOL. Ongoing monitoring should include disease activity based on
      symptoms, emergence of alternative diagnoses, and early referral of atypical and
      severe cases.

PMID- 17530681
TI  - Coffee, tea, and caffeine consumption and serum uric acid level: the third
      national health and nutrition examination survey.
AB  - OBJECTIVE: Coffee is one of the most widely consumed beverages in the world and
      may affect serum uric acid levels and risk of gout via various mechanisms. Our
      objective was to evaluate the relationship between coffee, tea, and caffeine
      intake and serum uric acid level in a nationally representative sample of men and
      women. METHODS: Using data from 14,758 participants ages >/=20 years in the Third
      National Health and Nutrition Examination Survey (1988-1994), we examined the
      relationship between coffee, tea, and caffeine intake and serum uric acid level
      using linear regression. Additionally, we examined the relationship with
      hyperuricemia (serum uric acid >7.0 mg/dl among men and >5.7 mg/dl among women)
      using logistic regression. Intake was assessed by a food frequency questionnaire.
      RESULTS: Serum uric acid level decreased with increasing coffee intake. After
      adjusting for age and sex, serum uric acid level associated with coffee intake of
      4 to 5 and >/=6 cups daily was lower than that associated with no intake by 0.26
      mg/dl (95% confidence interval [95% CI] 0.11, 0.41) and 0.43 mg/dl (95% CI 0.23,
      0.65; P for trend < 0.001), respectively. After adjusting for other covariates,
      the differences remained significant (P for trend < 0.001). Similarly, there was
      a modest inverse association between decaffeinated coffee intake and serum uric
      acid levels (multivariate P for trend 0.035). Total caffeine from coffee and
      other beverages and tea intake were not associated with serum uric acid levels
      (multivariate P for trend 0.15). The multivariate odds ratio for hyperuricemia in
      individuals with coffee intake >/=6 cups daily compared with those with no coffee
      use was 0.57 (95% CI 0.35, 0.94; P for trend 0.001). CONCLUSION: These findings
      from a nationally representative sample of US adults suggest that coffee
      consumption is associated with lower serum uric acid level and hyperuricemia
      frequency, but tea consumption is not. The inverse association with coffee
      appears to be via components of coffee other than caffeine.

PMID- 17530682
TI  - Quality of care for gout in the US needs improvement.
AB  - OBJECTIVE: To examine evidence-based quality indicators (QIs) in US veterans with
      gout diagnosis, and to examine the effect of demographics, heath care
      utilization/access, comorbid conditions, or physican characteristics as
      predictors of quality of gout care. METHODS: Using the Minneapolis Veterans
      Affairs electronic medical record system, we identified a cohort of veterans
      receiving medication to treat gout between January 1, 1999 and December 31, 2003,
      and evaluated 3 recently published evidence-based QIs for gout management: QI 1 =
      allopurinol dose <300 mg in gout patients with renal insufficiency, QI 2 = uric
      acid check within 6 months of starting a new allopurinol prescription, and QI 3 =
      complete blood count and creatine kinase check every 6 months for gout patients
      receiving prolonged colchicine therapy. We calculated the proportion of patients
      whose therapy adhered to each QI and to all applicable indicators (overall
      physician adherence). Logistic regression analysis examined association of
      overall physician adherence with sociodemographics, health care utilization,
      comorbidity, and provider characteristics. RESULTS: Of 3,658 patients with a
      diagnosis of gout, 663 patients qualified for examination of >/=1 QI. Of these
      663 patients, therapy in only 144 (22%) adhered to all applicable QIs; 59 (78%)
      of 76 adhered to QI 1, 155 (24%) of 643 adhered to QI 2, and 18 (35%) of 52
      adhered to QI 3. Overall physician adherence to QIs was significantly lower in
      older veterans and in those with more inpatient visits per year, but was higher
      in those with more primary care visits or more health care providers. CONCLUSION:
      Suboptimal physician adherence to QIs was seen for all 3 QIs tested in this
      cohort of veterans with gout. These findings can guide quality improvement
      efforts.

PMID- 17530683
TI  - Responder criteria for operant and cognitive-behavioral treatment of fibromyalgia
      syndrome.
AB  - OBJECTIVE: To predict the effects of cognitive-behavioral therapy (CBT) and
      operant-behavioral therapy (OBT) in fibromyalgia syndrome (FMS). METHODS: A total
      of 125 patients who fulfilled the American College of Rheumatology FMS criteria
      were randomly assigned to CBT (n = 42), OBT (n = 43), or attention placebo (AP; n
      = 40). The pretreatment to 12-month followup reliability change index was used to
      determine clinically meaningful changes in pain intensity and physical
      impairment. Multinominal logistic regression analyses were used to determine the
      predictors of improvement in pain intensity and physical impairment for the
      entire sample. Analyses of variance were computed to compare the characteristics
      of responders and nonresponders in each of the 3 interventions. RESULTS: At the
      12-month followup, 53.5%, 45.2%, and 5% of patients in the OBT, CBT, and AP
      groups, respectively, reported clinically meaningful improvements in pain
      intensity. Similarly, 58.1%, 38.1%, and 7.5% of patients treated with OBT, CBT,
      and AP, respectively, reported clinically significant improvements in physical
      impairment. Prior to treatment, the OBT physical impairment responders displayed
      significantly more pain behaviors, physical impairment, physician visits,
      solicitous spouse behaviors, and level of catastrophizing compared with
      nonresponders. The CBT physical impairment responders, compared with
      nonresponders, reported higher levels of affective distress, lower coping, less
      solicitous spouse behavior, and lower pain behaviors. CONCLUSION: The results of
      this study suggest that pretreatment patient characteristics are important
      predictors of treatment response and may serve as a basis for matching treatments
      to patient characteristics. Prospective outcome studies are needed to confirm
      whether the tailoring of treatment actually leads to better outcomes for patients
      with FMS.

PMID- 17530684
TI  - Clinical features and outcome of pediatric Wegener's granulomatosis.
AB  - OBJECTIVE: Wegener's granulomatosis (WG) is a predominantly small-vessel
      vasculitis associated with antineutrophil cytoplasmic antibodies (ANCAs). There
      are few reports describing its clinical features and outcome in children. We
      report on the experience at a single tertiary referral center over 21 years.
      METHODS: We conducted a retrospective chart review of all patients diagnosed with
      WG at The Hospital for Sick Children between 1984 and 2005. RESULTS: Twenty-five
      patients were identified. Median age at diagnosis and median followup were 14.5
      years and 32.7 months, respectively. Male-to-female ratio was 1:4. Median
      duration of symptoms before diagnosis was 2 months. Of 22 patients, 21 were ANCA
      positive during their disease course (classic ANCA 78.9%). Constitutional
      symptoms were the most common clinical feature at presentation (24 of 25).
      Glomerulonephritis was present in 22 patients at presentation. Only 1 of 11
      patients who presented with or developed renal impairment had normalization of
      serum creatinine. Upper airway involvement occurred in 21 patients at
      presentation and 24 over followup; only 1 had subglottic stenosis. Twenty
      patients had initial pulmonary involvement, most commonly nodules (44%) and
      pulmonary hemorrhage (44%). Five patients required ventilation for pulmonary
      hemorrhage. Four patients (16%) had venous thrombotic events (VTEs). Treatment
      included prednisone (100%), cyclophosphamide (76%), azathioprine (40%), and
      methotrexate (32%). CONCLUSION: Pediatric WG typically presents in adolescence
      and has a female predominance. Glomerulonephritis and pulmonary disease are
      common at diagnosis and frequently present as a pulmonary-renal syndrome. Loss of
      renal function is common and rarely completely reversible. As in adults, children
      with WG are at risk of VTEs.

PMID- 17530685
TI  - Whole blood viscosity and arterial thrombotic events in patients with systemic
      lupus erythematosus.
AB  - OBJECTIVE: To determine if whole blood viscosity (WBV), a rheologic variable
      contributing to risk of myocardial infarction and stroke in the general
      population, is elevated in patients with systemic lupus erythematosus (SLE),
      particularly SLE patients with a history of thrombotic or atherothrombotic
      events. Because the high rates of arterial and venous thrombosis in lupus cannot
      be explained by traditional risk factors, elevated WBV may be an easily
      measurable nontraditional risk factor to identify SLE patients at high risk for
      thrombotic events. METHODS: Sixty SLE patients (30 with a history of a thrombotic
      event) and 20 matched controls were recruited into the study. The thrombosis
      group was further subdivided into an arterial thrombosis group (n = 17). WBV
      values were determined at 9 different shear rates (1, 2, 5, 10, 50, 100, 150,
      300, and 1,000 seconds(-1)). WBV was then compared between groups by repeated
      measures analysis of variance. RESULTS: SLE patients with a history of arterial
      events had significantly elevated WBV relative to either controls (P = 0.022) or
      SLE patients without arterial events (P = 0.014). WBV in the total SLE group did
      not differ from controls. Differences in WBV were most prominent at lower shear
      rates (1, 2, 5, 10, 50, and 100 seconds(-1)). Anticoagulation, prednisone dose,
      and antiphospholipid antibodies did not significantly impact WBV. CONCLUSION: Our
      study demonstrated that WBV is selectively elevated in patients with SLE with a
      history of arterial events. Although this association is striking, longitudinal
      studies are needed to assess the positive predictive value of WBV for
      atherothrombotic events in SLE.

PMID- 17530686
TI  - Participation in patient self-management programs.
AB  - OBJECTIVE: Participation in evidenced-based arthritis self-management programs
      (SMPs) has not been well documented. The purpose of this study was to investigate
      the participation rate and participant characteristics in a closed cohort of
      subjects in a geographic region where arthritis SMPs have been offered multiple
      times and continuously for 2 decades. METHODS: Data were from osteoarthritis (OA)
      and rheumatoid arthritis subjects participating in the Arthritis, Rheumatism, and
      Aging Medical Information System (ARAMIS) who resided in the San Francisco (SF)
      Bay area who had responded to questions about ever participating in an SMP.
      Differences between participants and nonparticipants were examined by t-tests and
      chi-square tests. RESULTS: Questions added to the Health Assessment Questionnaire
      were returned by 1,176 patients; 618 resided in the SF Bay area. Of the SF Bay
      area sample, 41.9% had participated in an SMP. Small group SMPs, which had been
      offered multiple times, in diverse settings, continuously over the past 2
      decades, were attended by the highest proportion (28%) of participants.
      Characteristics of participants and nonparticipants in the SF Bay area were
      similar ( approximately 70 years old, 15 years of education, and the majority had
      OA [ approximately 72%]). However, a higher proportion of participants were white
      (88% versus 82%; P = 0.046) and female (82% versus 73%; P < 0.05). CONCLUSION:
      When arthritis SMPs were offered multiple times in diverse settings and
      continuously over many years, >40% of the cohort was reached. More research is
      needed with larger samples and different geographic regions to identify
      participation rates in more diverse populations.

PMID- 17530687
TI  - Schmorl's nodes: common, highly heritable, and related to lumbar disc disease.
AB  - OBJECTIVE: Schmorl's nodes (SN) are common, but little is known of their
      relationship with degenerative change and back pain or genetic and environmental
      factors influencing their expression. We studied healthy female twin volunteers
      to determine the prevalence and clinical features associated with SN. METHODS:
      Serial sagittal T1- and T2-weighted magnetic resonance images of the lower
      thoracic and lumbar spine were analyzed in 516 healthy female twins (150
      monozygotic and 366 dizygotic). The images were scored for lumbar degenerative
      change. Presence of SN was noted at cranial and caudal vertebral levels T9 to L5.
      Data on physical activity and back pain were collected by questionnaire.
      Heritability of SN was calculated using variance components modeling. RESULTS: SN
      were found in 30% of subjects. Of the 374 SN, 153 (41%) were in the lumbar spine
      and 221 (59%) were in the thoracic spine. SN heritability was >70%. There was a
      positive association between SN and lumbar disc disease (LDD). SN were more
      frequent in subjects with back pain (for >/=2 SN: odds ratio [OR] 2.68, 95%
      confidence interval [95% CI] 1.11-6.47, P = 0.03), but this was largely accounted
      for by the association of SN with LDD (OR 1.97, 95% CI 0.78-5.0, P = 0.15
      adjusted for LDD). No independent association of SN with back pain was
      identified. CONCLUSION: SN are common in middle-aged women and are strongly
      genetically determined. They are associated with lumbar degenerative change,
      which is a risk factor for back pain, but are not themselves an independent risk
      factor for back pain.

PMID- 17530688
TI  - Early aggressive care and delayed recovery from whiplash: isolated finding or
      reproducible result?
AB  - OBJECTIVE: To test the reproducibility of the finding that early intensive care
      for whiplash injuries is associated with delayed recovery. METHODS: We analyzed
      data from a cohort study of 1,693 Saskatchewan adults who sustained whiplash
      injuries between July 1, 1994 and December 31, 1994. We investigated 8 initial
      patterns of care that integrated type of provider (general practitioners,
      chiropractors, and specialists) and number of visits (low versus high
      utilization). Cox models were used to estimate the association between patterns
      of care and time to recovery while controlling for injury severity and other
      confounders. RESULTS: Patients in the low-utilization general practitioner group
      and those in the general medical group had the fastest recovery even after
      controlling for important prognostic factors. Compared with the low-utilization
      general practitioner group, the 1-year rate of recovery in the high-utilization
      chiropractic group was 25% slower (adjusted hazard rate ratio [HRR] 0.75, 95%
      confidence interval [95% CI] 0.54-1.04), in the low-utilization general
      practitioner plus chiropractic group the rate was 26% slower (HRR 0.74, 95% CI
      0.60-0.93), and in the high-utilization general practitioner plus chiropractic
      combined group the rate was 36% slower (HRR 0.64, 95% CI 0.50-0.83). CONCLUSION:
      The observation that intensive health care utilization early after a whiplash
      injury is associated with slower recovery was reproduced in an independent cohort
      of patients. The results add to the body of evidence suggesting that early
      aggressive treatment of whiplash injuries does not promote faster recovery. In
      particular, the combination of chiropractic and general practitioner care
      significantly reduces the rate of recovery.

PMID- 17530689
TI  - Exploring the use of videotaped objective structured clinical examination in the
      assessment of joint examination skills of medical students.
AB  - OBJECTIVE: Objective structured clinical examination (OSCE) is a key part of
      medical student assessment. Currently, assessment is performed by medical
      examiners in situ. Our objective was to determine whether assessment by
      videotaped OSCE is as reliable as live OSCE assessment. METHODS: Participants
      were 95 undergraduate medical students attending their musculoskeletal week at
      Freeman Hospital, Newcastle (UK). Student performance on OSCE stations for
      shoulder or knee examinations was assessed by experienced rheumatologists. The
      stations were also videotaped and scored by a rheumatologist independently. The
      examinations consisted of a 14-item checklist and a global rating scale (GRS).
      RESULTS: Mean values for the shoulder OSCE checklist were 17.9 by live assessment
      and 17.4 by video (n = 50), and 20.9 and 20.0 for live and video knee assessment,
      respectively (n = 45). Intraclass correlation coefficients for shoulder and knee
      checklists were 0.55 and 0.58, respectively, indicating moderate reliability
      between live and video scores for the OSCE checklists. GRS scores were less
      reliable than checklist scores. There was 84% agreement in the classification of
      examination grades between live and video checklist scores for the shoulder and
      87% agreement for the knee (kappa = 0.43 and 0.51, respectively; P < 0.001).
      CONCLUSION: Video OSCE has the potential to be reliable and offers some
      advantages over live OSCE including more efficient use of examiners' time,
      increased fairness, and better monitoring of standards across various
      schools/sites. However, further work is needed to support our findings and to
      implement and evaluate the quality assurance issues identified in this work
      before justifiable recommendations can be made.

PMID- 17530690
TI  - Possible role of streptococcal infection in flares of juvenile idiopathic
      arthritis.

PMID- 17530691
TI  - Late-onset gastrointestinal pain in juvenile dermatomyositis as a manifestation
      of ischemic ulceration from chronic endarteropathy.

PMID- 17530692
TI  - Rheumatologists, where are we in the global health picture: a call to action.

PMID- 17530695
TI  - T cell alterations and lymphoid neogenesis favoring autoimmunity in Wegener's
      granulomatosis.

PMID- 17530696
TI  - Morphological differentiation of aboriginal human populations from Tierra del
      Fuego (Patagonia): implications for South American peopling.
AB  - This study aims to integrate the craniofacial morphological variation of southern
      South American populations with the results of mtDNA haplogroup variation, to
      discuss the South America peopling. Because the causes of morphological
      differentiation of Fueguian populations are still a controversial subject, the
      comparison with neutral variation could contribute to elucidate them. Samples of
      human remains from South America regions were used to analyze the evolutionary
      relationships. Several craniofacial traits observed in frontal and lateral view
      were analyzed by means of geometric morphometrics techniques, and the
      evolutionary relationships based on morphological and molecular data were
      established in base to ordination analyses. The results from the facial skeleton
      agree with those obtained from mtDNA haplogroup frequencies, with La Pampa/Chaco
      samples detached from the Patagonian samples. Hence, the same mechanism that
      accounts for the pattern of frequency of haplogroups could explain the variation
      found in facial skeleton among the samples. It is suggested that such geographic
      pattern of craniofacial and molecular diversity may reflect the effect of genetic
      drift that occurred in the small founding populations isolated by distance or
      geographic barriers. Conversely, the results obtained using the traits from the
      lateral view slightly differ from the molecular results, showing differences
      between southernmost Patagonian and the other samples. Therefore, mechanisms
      other than genetic drift (e.g., natural selection) could have acted to shape the
      pattern observed in some craniofacial structures present in the lateral view,
      characterized by the fact that the southernmost Patagonian samples display the
      most robust and dolichocephalic crania.

PMID- 17530697
TI  - Protection of obstetric dimensions in a small-bodied human sample.
AB  - In human females, the bony pelvis must find a balance between being small
      (narrow) for efficient bipedal locomotion, and being large to accommodate a
      relatively large newborn. It has been shown that within a given population,
      taller/larger-bodied women have larger pelvic canals. This study investigates
      whether in a population where small body size is the norm, pelvic geometry (size
      and shape), on average, shows accommodation to protect the obstetric canal.
      Osteometric data were collected from the pelves, femora, and clavicles (body size
      indicators) of adult skeletons representing a range of adult body size. Samples
      include Holocene Later Stone Age (LSA) foragers from southern Africa (n = 28
      females, 31 males), Portuguese from the Coimbra-identified skeletal collection
      (CISC) (n = 40 females, 40 males) and European-Americans from the Hamann-Todd
      osteological collection (H-T) (n = 40 females, 40 males). Patterns of sexual
      dimorphism are similar in the samples. Univariate and multivariate analyses of
      raw and Mosimann shape-variables indicate that compared to the CISC and H-T
      females, the LSA females have relatively large midplane and outlet canal planes
      (particularly posterior and A-P lengths). The LSA males also follow this pattern,
      although with absolutely smaller pelves in multivariate space. The CISC females,
      who have equally small stature, but larger body mass, do not show the same type
      of pelvic canal size and shape accommodation. The results suggest that adaptive
      allometric modeling in at least some small-bodied populations protects the
      obstetric canal. These findings support the use of population-specific attributes
      in the clinical evaluation of obstetric risk.

PMID- 17530698
TI  - Clinical Images: rheumatoid nodules in synovium.

PMID- 17530699
TI  - Human colonization of the central territory of Argentina: design matrix models
      and craniometric evidence.
AB  - In this study we test several hypotheses about the peopling of the central
      territory of Argentina, archaeologically known as Sierras Centrales, by testing
      the association between four alternative models of the peopling of the area and
      cranial morphological variation through distance and matrix correlation analyses.
      Our results show that the ancient inhabitants of Sierras Centrales demonstrated
      close morphological similarities with the Patagonian and Tierra del Fuego
      populations. Moreover, the correlation and partial correlation analyses suggest
      that the peopling of the Sierras Centrales most likely took place as a migratory
      wave proceeding from the present area of Northeastern Argentina, and continued
      southward to Patagonia and Tierra del Fuego.

PMID- 17530700
TI  - Diagnostic value of micro-CT in comparison with histology in the qualitative
      assessment of historical human skull bone pathologies.
AB  - Cases of pathologically changed bone might constitute a diagnostic pitfall and
      frequently need histological methods to be etiologically properly evaluated. With
      micro-computed tomography (microCT), a new epoch of 2D and 3D imaging has been
      launched. We evaluated the diagnostic investigation of this analytical method
      versus well established histological investigations of historical human bone.
      Pathological changes due to various etiologies (infectious, traumatic,
      endocrinological, neoplasia) observed in autopsy-based macerated human skulls
      (Galler Collection, Natural History Museum Basel, Switzerland) were investigated
      by microCT and compared with histological thin ground sections using polarized
      light. Micro-CT images visualize the architecture of the bone with high spatial
      resolution without preparation or destruction of the sample in the area to be
      sectioned. Changes in the bone surfaces as well as alterations of the diploe can
      be assessed. However, morphological patterns caused by reactive response, such as
      typical arrangements of collagen fibers, can only be visualized by the
      microscopic investigation of thin ground sections using polarized light. A great
      advantage of microCT is the high number of slices obtained so that spatial
      differences within the areas of the specimen become visible. Micro-CT is a
      valuable tool for the diagnosis of vestiges of skull bone diseases. Its
      advantages over histology are the fast, automated image acquisition and the fact
      that the specimen is not completely destroyed. Only excision of the area to be
      scanned is necessary, if the specimen is too large to be scanned as a whole.
      Further, the 3D visualization of the micro-architecture allows an easy
      orientation within the sample, for example, for the choice of the location of the
      histological slices. However, the need to differentiate woven from lamellar bone
      still makes histology an indispensable method.

PMID- 17530701
TI  - New distal embolic protection device the FiberNet 3 dimensional filter: first
      carotid human study.
AB  - OBJECTIVE: Evaluate the performance and safety of the FiberNet Embolic Protection
      System during carotid artery intervention. BACKGROUND: Carotid Angioplasty and
      Stenting (CAS) can be proposed to treat the majority of carotid stenoses. Brain
      embolization takes place and routine use of Embolic Protection Devices (EPD) is
      warranted. Many EPDs have significant limitations, which may be addressed by a
      new EPD, the FiberNet (Lumen Biomedical, Plymouth, MN). METHODS: The system
      consists of a 3-dimensional expandable filter made of fibers, which expand
      radially, mounted onto a 0.014'' wire and retrieval catheter. FiberNet can
      capture particles as small as 40 microm without compromising flow. RESULTS: 35
      lesions treated in 34 patients. Male 67.6%. Age: 71.4 +/- 8.8 (50-85). Average
      stenosis 84.5% +/- 7.9 (70-99). 29.4% were symptomatic. Technical success: 34/35
      (97%). No stroke or death within 30 days. Neurological events: two permanent
      amaurosis, one amaurosis fugax. All samples visually contained significant
      amounts of emboli. The mean surface area of debris caught was 63.8 mm(2) (37.7
      107.5). Comparisons were made with other EPDs. The mean surface area of debris
      caught was 12.2 mm(2) (2.7-34.3). No changes were noted in CT/MRI at 30-day post
      procedure. CONCLUSION: The first human use of this new novel EPD in carotid
      artery stenting is encouraging. The FiberNet was easy to use and confirmed the
      ability to capture particles less than 100 microm. The feasibility of the
      FiberNet has been demonstrated. Additional patients will demonstrate the overall
      safety and efficacy of this new EPD device.

PMID- 17530702
TI  - Are we at a stage to predict autoimmune rheumatic diseases?

PMID- 17530703
TI  - Interaction between smoking, the shared epitope, and anti-cyclic citrullinated
      peptide: a mixed picture in three large North American rheumatoid arthritis
      cohorts.
AB  - OBJECTIVE: Recently, Swedish members of the Epidemiological Investigation of
      Rheumatoid Arthritis (EIRA) provided evidence that smoking may trigger RA
      specific immune reactions to citrullinated protein in carriers of HLA-DR shared
      epitope alleles. In an effort to confirm this interaction between smoking and
      shared epitope alleles, we performed a case-only analysis of 3 North American RA
      cohorts. METHODS: A total of 2,476 white patients with RA were studied, 1,105
      from the North American Rheumatoid Arthritis Consortium (NARAC) family
      collection, 753 from the National Inception Cohort of Rheumatoid Arthritis
      Patients (Inception Cohort), and 618 from the Study of New Onset Rheumatoid
      Arthritis (SONORA). All patients were HLA-DRB1 typed, and tested for anti-cyclic
      citrullinated peptide (anti-CCP) and rheumatoid factor. Information about smoking
      history was obtained by questionnaire. RESULTS: A significant association was
      found between smoking and the presence of anti-CCP in the NARAC and the Inception
      Cohort, but not in the SONORA. The shared epitope alleles consistently correlated
      with anti-CCP in all 3 populations. Using multiple logistic regression analyses,
      shared epitope alleles were still the most significant risk factor for anti-CCP
      positivity. Weak evidence of gene-environment interaction between smoking and
      shared epitope alleles for anti-CCP formation was found only in the NARAC.
      CONCLUSION: Unlike the EIRA data, we could not confirm a major gene-environment
      interaction for anti-CCP formation between shared epitope alleles and smoking in
      3 North American RA cohorts. Our data indicate a need for further studies to
      address the full range of environmental factors other than smoking that may be
      associated with citrullination and RA.

PMID- 17530704
TI  - Anti-tumor necrosis factor alpha therapy and the risk of serious bacterial
      infections in elderly patients with rheumatoid arthritis.
AB  - OBJECTIVE: To assess the association between the initiation of anti-tumor
      necrosis factor alpha (anti-TNFalpha) therapy and the risk of serious bacterial
      infections in routine care. METHODS: This was a cohort study of patients with
      rheumatoid arthritis (RA) in whom specific disease-modifying antirheumatic drugs
      (DMARDs) were initiated. Patients were Medicare beneficiaries ages 65 years and
      older (mean age 76.5 years) who were concurrently enrolled in the Pharmaceutical
      Assistance Contract for the Elderly provided by the state of Pennsylvania. A
      total of 15,597 RA patients in whom a DMARD was initiated between January 1, 1995
      and December 31, 2003 were identified using linked data on all prescription drug
      dispensings, physician services, and hospitalizations. Initiation of anti
      TNFalpha therapy, cytotoxic agents other than methotrexate (MTX), noncytotoxic
      agents, and glucocorticoids was compared with initiation of MTX. The main outcome
      measure was serious bacterial infections that required hospitalization. RESULTS:
      The incidence of serious bacterial infections was, on average, 2.2 per 100
      patient-years in this population (95% confidence interval [95% CI] 2.0-2.4).
      Glucocorticoid use doubled the rate of serious bacterial infections as compared
      with MTX use, independent of previous DMARD use (rate ratio [RR] 2.1 [95% CI 1.5
      3.1]), with a clear dose-response relationship for dosages >5 mg/day (for < or =
      5 mg/day, RR 1.34; for 6-9 mg/day, RR 1.53; for 10-19 mg/day, RR 2.97; and for >
      or = 20 mg/day, RR 5.48 [P for trend < 0.0001]). Adjusted models showed no
      increase in the rate of serious infections among initiators of anti-TNFalpha
      therapy (RR 1.0 [95% CI 0.6-1.7]) or other DMARDs as compared with initiators of
      MTX. CONCLUSION: In a large cohort of patients with RA, we found no increase in
      serious bacterial infections among users of anti-TNFalpha therapy compared with
      users of MTX. Glucocorticoid use was associated with a dose-dependent increase in
      such infections.

PMID- 17530705
TI  - A clinical pharmacogenetic model to predict the efficacy of methotrexate
      monotherapy in recent-onset rheumatoid arthritis.
AB  - OBJECTIVE: To develop a clinical pharmacogenetic model to predict the efficacy of
      methotrexate (MTX) in rheumatoid arthritis (RA). METHODS: Two hundred five
      patients with newly diagnosed RA and active disease were treated with MTX
      (initiated at a dosage of 7.5 mg/week and increased to 15 mg/week after 4 weeks)
      and folic acid (1 mg/day). If the Disease Activity Score (DAS) was >2.4 at 3
      months, the dosage of MTX was increased up to 25 mg/week. Twenty-four baseline
      variables possibly influencing disease state and drug response were selected. In
      addition, 17 polymorphisms in 13 genes related to the MTX mechanism of action,
      purine and pyrimidine synthesis, were determined. Factors were compared between
      responders (defined as patients with a DAS < or = 2.4 at 6 months) and
      nonresponders. In case of differences, a stepwise selection procedure identified
      the predictors for response. A clinical score was designed by simplifying
      regression coefficients of the independent variables. Cutoff levels were chosen
      based on the clinical score, and positive and negative response rates were
      calculated. An evaluation of the model was performed in a second group of
      patients. RESULTS: The model for MTX efficacy consisted of sex, rheumatoid factor
      and smoking status, the DAS, and 4 polymorphisms in the AMPD1, ATIC, ITPA, and
      MTHFD1 genes. This prediction model was transformed into a scoring system ranging
      from 0 to 11.5. Scores of < or = 3.5 had a true positive response rate of 95%.
      Scores of > or = 6 had a true negative response rate of 86%. Sixty percent of the
      patients were categorized as either responders or nonresponders, whereas 32% of
      the patients were categorized using a nongenetic model. Evaluation of the model
      in 38 additional patients with RA supported the results. CONCLUSION: This study
      established a model for predicting the efficacy of MTX in patients with RA. This
      pharmacogenetic model may lead to better-tailored initial treatment decisions in
      patients with RA.

PMID- 17530706
TI  - Tumor necrosis factor alpha activates release of B lymphocyte stimulator by
      neutrophils infiltrating the rheumatoid joint.
AB  - OBJECTIVE: The tumor necrosis factor (TNF) family member B lymphocyte stimulator
      (BLyS) is an important regulator of B cell-dependent autoimmunity. Similar to
      other TNF family members, it is generally expressed as a transmembrane protein
      and cleaved from the surface to release its active soluble form. This study was
      undertaken to investigate the expression of BLyS and regulation of BLyS release
      from the surface of neutrophils infiltrating the rheumatoid joint. METHODS: BLyS
      expression was studied in neutrophils from the synovial fluid and peripheral
      blood of patients with rheumatoid arthritis (RA) and healthy controls, by flow
      cytometry, Western blotting, and immunofluorescence analyses. Peripheral blood
      neutrophils cultured with 50% RA synovial fluid were study for membrane
      expression of BLyS. Neutrophils were exposed to a range of proinflammatory
      cytokines to study the mechanisms of surface loss of BLyS. RESULTS: Expression of
      BLyS was detected on the surface of peripheral blood neutrophils from both RA
      patients and healthy controls, whereas BLyS expression on synovial fluid
      neutrophils was very low. Constitutive expression of BLyS was observed in
      neutrophils, both on the cell membrane and in intracellular stores; however, BLyS
      release from each of these sites was found to be regulated independently. Of the
      various cytokine stimuli, only TNFalpha triggered release of BLyS from the
      neutrophil membrane. This process led to release of physiologically relevant
      quantities of soluble BLyS, which was dependent on the presence of the pro
      protein convertase furin. In contrast, stimulation of neutrophils with
      granulocyte colony-stimulating factor induced BLyS release from the intracellular
      stores. Incubation of peripheral blood neutrophils with RA synovial fluid led to
      TNFalpha-dependent shedding of BLyS from the cell surface. CONCLUSION: These
      findings indicate that as neutrophils enter the site of inflammation, they
      release surface-expressed BLyS in a TNFalpha-dependent manner, and thus may
      contribute to local stimulation of autoimmune B cell responses.

PMID- 17530707
TI  - Interleukin-18 induces angiogenic factors in rheumatoid arthritis synovial tissue
      fibroblasts via distinct signaling pathways.
AB  - OBJECTIVE: Interleukin-18 (IL-18) is a proinflammatory cytokine implicated in the
      pathogenesis of rheumatoid arthritis (RA). This study was undertaken to examine
      the role of IL-18 in up-regulating secretion of the angiogenic factors stromal
      cell-derived factor 1alpha (SDF-1alpha)/CXCL12, monocyte chemoattractant protein
      1 (MCP-1)/CCL2, and vascular endothelial growth factor (VEGF) in RA synovial
      tissue (ST) fibroblasts, and the underlying signaling mechanisms involved.
      METHODS: We used enzyme-linked immunosorbent assays, Western blotting, and
      chemical inhibitors/antisense oligodeoxynucleotides to signaling intermediates to
      assess the role of IL-18. RESULTS: IL-18 significantly enhanced the production of
      SDF-1alpha/CXCL12, MCP-1/CCL2, and VEGF in RA ST fibroblasts, in a time- and
      concentration-dependent manner. IL-18-induced SDF-1alpha/CXCL12 up-regulation was
      dependent on JNK, p38 MAPK, phosphatidylinositol 3-kinase (PI3K), and NFkappaB.
      While IL-18-induced production of SDF-1alpha/CXCL12 was also dependent on protein
      kinase Cdelta (PKCdelta), production of MCP-1/CCL2 was dependent on PKCalpha, not
      PKCdelta. Additionally, RA ST fibroblast IL-18-induced MCP-1/CCL2 production was
      mediated by JNK, PI3K, and NFkappaB. In contrast, IL-18 did not induce secretion
      of RA ST fibroblast MCP-1/CCL2 or VEGF via p38 MAPK. IL-18-induced RA ST
      fibroblast production of VEGF was mediated mainly by JNK-2, PKCalpha, and
      NFkappaB. IL-18 induced phosphorylation of JNK, PKCdelta, p38 MAPK, and
      activating transcription factor 2 (ATF-2) in RA ST fibroblasts in a time
      dependent manner, with JNK-2 being upstream of PKCdelta, ATF-2, and NFkappaB.
      CONCLUSION: These data support the notion that IL-18 has a unique role in
      inducing the secretion of angiogenic SDF-1alpha/CXCL12, MCP-1/CCL2, and VEGF in
      RA ST fibroblasts, via distinct signaling intermediates.

PMID- 17530708
TI  - Female mice are more susceptible to developing inflammatory disorders due to
      impaired transforming growth factor beta signaling in salivary glands.
AB  - OBJECTIVE: Transforming growth factor beta (TGFbeta) plays a key role in the
      onset and resolution of autoimmune diseases and chronic inflammation. The aim of
      this study was to delineate the precise function of TGFbeta signaling in salivary
      gland inflammation. METHODS: We impaired TGFbeta signaling in mouse salivary
      glands by conditionally inactivating expression of TGFbeta receptor type I
      (TGFbetaRI), either by using mouse mammary tumor virus-Cre mice or by delivering
      adenoviral vector containing Cre to mouse salivary glands via retrograde infusion
      of the cannulated main excretory ducts of submandibular glands. RESULTS:
      TGFbetaRI-conditional knockout (TGFbetaRI-coko) mice were born normal; however,
      female TGFbetaRI-coko mice developed severe multifocal inflammation in salivary
      and mammary glands and in the heart. The inflammatory disorder affected normal
      growth and resulted in the death of the mice at ages 4-5 weeks. Interestingly,
      male TGFbetaRI-coko mice did not exhibit any signs of inflammation. The female
      TGFbetaRI-coko mice also showed an increase in Th1 proinflammatory cytokines in
      salivary glands and exhibited an up-regulation of peripheral T cells. In
      addition, these mice showed an atypical distribution of aquaporin 5 in their
      salivary glands, suggesting likely secretory impairment. Administration of an
      adenoviral vector encoding Cre recombinase into the salivary glands resulted in
      inflammatory foci only in the glands of female TGFbetaRI-loxP-flanked (floxed)
      mice (TGFbetaRI-f/f mice), but not in those of male and female wild-type mice or
      male TGFbetaRI-f/f mice. CONCLUSION: These results suggest that female mice are
      uniquely more susceptible to developing inflammatory disorders due to impaired
      TGFbeta signaling in their salivary glands.

PMID- 17530709
TI  - Targeted mast cell silencing protects against joint destruction and angiogenesis
      in experimental arthritis in mice.
AB  - OBJECTIVE: Induction of arthritis with autoantibodies against glucose-6-phosphate
      isomerase (GPI) is entirely independent of T cells and B cells but is strictly
      dependent on the presence of mast cells. Here, we used this disease model to
      analyze whether exclusive intraarticular mast cell reconstitution is sufficient
      for disease induction and whether targeted mast cell silencing can prevent
      neoangiogenesis and joint destruction, 2 hallmarks of rheumatoid arthritis.
      METHODS: Ankle swelling and clinical index scores were determined after injection
      of either K/BxN mouse-derived serum or control serum in wild-type Kit(+)/Kit(+)
      mice, congenic mast cell-deficient Kit(W)/Kit(W-v) mice, or mast cell-deficient
      Kit(W)/Kit(W-v) mice reconstituted with mast cells, either by intraperitoneal or
      selective intraarticular injection. Angiogenesis was quantified in vivo by
      measuring activated alphavbeta3 integrin using (18)F-galacto-RGD and positron
      emission tomography. In addition, staining of joint tissue with hematoxylin and
      eosin, Giemsa, beta3, and alpha-actin was performed. The effect of mast cell
      stabilization by treatment with cromolyn or salbutamol was investigated in
      C57BL/6 or BALB/c mice. RESULTS: Comparing wild-type mice, mast cell-deficient
      Kit(W)/Kit(W-v) mice, and mast cell-reconstituted Kit(W)/Kit(W-v) mice, we first
      showed that intraarticular and intraperitoneal mast cell engraftment fully
      restores susceptibility to antibody-induced arthritis, angiogenesis, and
      alphavbeta3 integrin activation. Importantly, selective mast cell silencing with
      either salbutamol or cromolyn prevented alphavbeta3 integrin activation,
      angiogenesis, and joint destruction. CONCLUSION: Mast cell engraftment fully
      restores susceptibility to alphavbeta3 integrin activation, angiogenesis, and
      joint destruction in GPI antibody-induced arthritis. Importantly, selective mast
      cell stabilization prevents alphavbeta3 integrin activation, angiogenesis, and
      joint destruction.

PMID- 17530710
TI  - The role of vascular cell adhesion molecule 1/ very late activation antigen 4 in
      endothelial progenitor cell recruitment to rheumatoid arthritis synovium.
AB  - OBJECTIVE: Marrow-derived endothelial progenitor cells (EPCs) are important in
      the neovascularization that occurs in diverse conditions such as cardiovascular
      disorders, inflammatory diseases, and neoplasms. In rheumatoid arthritis (RA),
      synovial neovascularization propels disease by nourishing the inflamed and
      hyperproliferative synovium. This study was undertaken to investigate the
      hypothesis that EPCs selectively home to inflamed joint tissue and may perpetuate
      synovial neovascularization. METHODS: In a collagen-induced arthritis (CIA)
      model, neovascularization and EPC accumulation in mouse ankle synovium was
      measured. In an antibody-induced arthritis model, EPC recruitment to inflamed
      synovium was evaluated. In a chimeric SCID mouse/human synovial tissue (ST)
      model, mice were engrafted subcutaneously with human ST, and EPC homing to grafts
      was assessed 2 days later. EPC adhesion to RA fibroblasts and RA ST was evaluated
      in vitro. RESULTS: In mice with CIA, cells bearing EPC markers were significantly
      increased in peripheral blood and accumulated in inflamed synovial pannus. EPCs
      were 4-fold more numerous in inflamed synovium from mice with anti-type II
      collagen antibody-induced arthritis versus controls. In SCID mice, EPC homing to
      RA ST was 3-fold greater than to normal synovium. Antibody neutralization of
      vascular cell adhesion molecule 1 (VCAM-1) and its ligand component alpha4
      integrin potently inhibited EPC adhesion to RA fibroblasts and RA ST
      cryosections. CONCLUSION: These data demonstrate the selective recruitment of
      EPCs to inflamed joint tissue. The VCAM-1/very late activation antigen 4 adhesive
      system critically mediates EPC adhesion to cultured RA fibroblasts and to RA ST
      cryosections. These findings provide evidence of a possible role of EPCs in the
      synovial neovascularization that is critical to RA pathogenesis.

PMID- 17530711
TI  - Fluvastatin reverses endothelial dysfunction and increased vascular oxidative
      stress in rat adjuvant-induced arthritis.
AB  - OBJECTIVE: To investigate the effect of statins on vascular dysfunction in rat
      adjuvant-induced arthritis (AIA). METHODS: Fluvastatin (5 mg/kg/day) was
      administered orally to rats with AIA, for 21 days after the onset of arthritis.
      The vasodilatory response to acetylcholine of aortic rings isolated from rats
      with AIA that were not treated or were treated with fluvastatin and from normal
      rats was determined. The amounts of 4-hydroxy-2-nonenal (HNE) and nitrotyrosine
      in aortas were measured by Western blotting. In vitro and in situ superoxide
      production in aortas was evaluated based on fluorogenic oxidation of
      dihydroethidium to ethidium. Expression of NAD(P)H components and endothelial
      nitric oxide synthase (eNOS) in aortas was examined by real-time reverse
      transcriptase-polymerase chain reaction and Western blotting. Serum levels of
      tetrahydrobiopterin, a critical eNOS cofactor, were determined by high
      performance liquid chromatography. RESULTS: Fluvastatin reversed endothelial
      dysfunction in AIA without affecting the clinical severity of arthritis or serum
      cholesterol concentration. Fluvastatin reduced the amounts of HNE and
      nitrotyrosine in the aorta, and the levels of superoxide expressed in endothelial
      cells and smooth muscle cells in the tissue, in rats with AIA. NADH- or L
      arginine-induced superoxide production was not observed in the aortic samples
      from fluvastatin-treated rats with AIA. Fluvastatin decreased the levels of
      expression of messenger RNA for p22phox, a NAD(P)H oxidase component, in the
      aortas of rats with AIA, but did not affect the expression of eNOS. Serum levels
      of tetrahydrobiopterin were significantly reduced in rats with AIA, and were
      increased by administration of fluvastatin. CONCLUSION: Our findings demonstrate
      that fluvastatin has potent vascular protective effects in AIA and provide
      additional scientific rationale for the use of statins to reduce cardiovascular
      mortality in patients with rheumatoid arthritis.

PMID- 17530712
TI  - Activation of invariant natural killer T cells by synthetic glycolipid ligands
      suppresses autoantibody-induced arthritis.
AB  - OBJECTIVE: Stimulation of invariant natural killer T (iNKT) cells with SGL-S23, a
      novel synthetic glycolipid analog of alpha-galactosylceramide with an elongated
      sphingosine chain, has been shown to strongly suppress K/BxN serum transfer
      arthritis. This study was designed to evaluate the protective effects of SGL-S23
      in an effector phase of arthritis. METHODS: To induce arthritis, C57BL/6 mice
      were injected with 150 mul of serum from K/BxN mice (KRN TCR-transgenic mice
      crossed with nonobese diabetic mice). Subsequently, synthetic glycolipid ligands
      were administered intraperitoneally twice, either 3 times starting on day 0 (the
      day of K/BxN serum injection) or twice starting on day 3. Neutralizing antibody
      against interferon-gamma (IFNgamma) interleukin-4 (IL-4), IL-10, or transforming
      growth factor beta was administered 4 hours before injection of SGL-S23.
      Recombinant IFNgamma was administered subcutaneously every day. The severity of
      arthritis was monitored using a macroscopic scoring system. Cytokine production
      and plasma histamine levels were measured by enzyme-linked immunosorbent assay.
      RESULTS: SGL-S23 strongly suppressed K/BxN serum transfer arthritis by inhibiting
      inflammatory cell infiltration and subsequent destruction of cartilage and bone.
      The inhibitory effect mediated by SGL-S23 was abolished by neutralization of
      IFNgamma. Systemic administration of IFNgamma prevented the development of
      inflammatory arthritis. Histamine release was suppressed by administration of SGL
      S23 or IFNgamma. Degranulated mast cells in the synovium were significantly
      reduced in SGL-S23-treated mice, suggesting that suppression of mast cell
      activation contributed to the inhibition of arthritis. CONCLUSION: These findings
      suggest that activation of iNKT cells with glycolipid ligands holds promise with
      regard to the treatment of autoimmune diseases such as rheumatoid arthritis. SGL
      S23 has clinical benefit over alpha-galactosylceramide since it induces a weaker
      cytokine production response in iNKT cells, therefore reducing potential side
      effects caused by excessive cytokine release.

PMID- 17530713
TI  - Serum matrix metalloproteinase 3 is an independent predictor of structural damage
      progression in patients with ankylosing spondylitis.
AB  - OBJECTIVE: In prospective studies, only baseline radiographic damage has been
      identified as an independent predictor of radiographic progression in ankylosing
      spondylitis (AS). Several biomarkers have been identified as independent
      predictors of radiographic progression in rheumatoid arthritis, however, and
      these may be of use in AS. This study was undertaken to analyze serologic
      biomarkers as predictors of radiographic progression in AS. METHODS: We measured
      a panel of biomarkers reflecting cartilage turnover and osteoclasis. These
      biomarkers were cartilage oligomeric matrix protein, human cartilage gp-39 (YKL
      40), type II collagen epitopes detected by the C2C and C1,2C degradation assays
      and the CPII synthesis assay, aggrecan 846 epitope, osteoprotegerin, and matrix
      metalloproteinase 3 (MMP-3). The analysis was performed in a cohort of AS
      patients from the Netherlands, Belgium, and France enrolled in a longitudinal
      study, the Outcome Assessments in Ankylosing Spondylitis International Study. We
      examined 2-year radiographic progression data scored using the modified Stoke AS
      Spine Score (mSASSS). RESULTS: Complete data were available on 97 patients. Only
      the biomarkers YKL-40 and MMP-3 showed weak to moderate univariate correlation
      with 2-year progression. After adjustment for sex, age, disease duration, C
      reactive protein level, and baseline mSASSS, only MMP-3 was significantly
      associated with 2-year progression (beta = 0.29, P = 0.004). Logistic regression
      analysis revealed MMP-3 (cutoff 68 ng/ml; odds ratio 9.4 [95% confidence interval
      1.6-56]) and baseline mSASSS (cutoff 10 mSASSS units; odds ratio 18.6 [95%
      confidence interval 2.5-138]) as the only independent predictors of 2-year
      progression (cutoff 3 mSASSS units; model R(2) = 50%). MMP-3 was primarily
      contributory in patients who already had substantial baseline damage (>10 mSASSS
      units). CONCLUSION: These results indicate that MMP-3 is a significant
      independent predictor of radiographic progression in patients with AS,
      particularly in those with preexisting radiographic damage.

PMID- 17530714
TI  - Global analyses of gene expression in early experimental osteoarthritis.
AB  - OBJECTIVE: To analyze genome-wide changes in chondrocyte gene expression in a
      surgically induced model of early osteoarthritis (OA) in rats, to assess the
      similarity of this model to human OA, and to identify genes and mechanisms
      leading to OA pathogenesis. METHODS: OA was surgically induced in 5 rats by
      anterior cruciate ligament transection and partial medial meniscectomy. Sham
      surgery was performed in 5 additional animals, which were used as controls. Both
      groups underwent 4 weeks of forced mobilization, 3 times per week. RNA was
      extracted directly from articular chondrocytes in the OA (operated),
      contralateral, and sham-operated knees. Affymetrix GeneChip expression arrays
      were used to assess genome-wide changes in gene expression. Expression patterns
      of selected dysregulated genes, including Col2a1, Mmp13, Adamts5, Ctsc, Ptges,
      and Cxcr4, were validated by real-time polymerase chain reaction,
      immunofluorescence, or immunohistochemistry 2, 4, and 8 weeks after surgery.
      RESULTS: After normalization, comparison of OA and sham-operated samples showed
      1,619 differentially expressed probe sets with changes in their levels of
      expression > or = 1.5-fold, 722 with changes > or = 2-fold, 135 with changes > or
      = 4-fold, and 20 with changes of 8-fold. Dysregulated genes known to be involved
      in human OA included Mmp13, Adamts5, and Ptgs2, among others. Several
      dysregulated genes (e.g., Reln, Phex, and Ltbp2) had been identified in our
      earlier microarray study of hypertrophic chondrocyte differentiation. Other genes
      involved in cytokine and chemokine signaling, including Cxcr4 and Ccl2, were
      identified. Changes in gene expression were also observed in the contralateral
      knee, validating the sham operation as the appropriate control. CONCLUSION: Our
      results demonstrate that the animal model mimics gene expression changes seen in
      human OA, supporting the relevance of newly identified genes and pathways to
      early human OA. We propose new avenues for OA pathogenesis research and potential
      targets for novel OA treatments, including cathepsins and cytokine, chemokine,
      and growth factor signaling pathways, in addition to factors controlling the
      progression of chondrocyte differentiation.

PMID- 17530715
TI  - Chondrogenic differentiation of bovine synovium: bone morphogenetic proteins 2
      and 7 and transforming growth factor beta1 induce the formation of different
      types of cartilaginous tissue.
AB  - OBJECTIVE: To compare the potential of bone morphogenetic proteins 2 and 7 (BMP-2
      and BMP-7) and transforming growth factor beta1 (TGFbeta1) to effect the
      chondrogenic differentiation of synovial explants by analyzing the histologic,
      biochemical, and gene expression characteristics of the cartilaginous tissues
      formed. METHODS: Synovial explants derived from the metacarpal joints of calves
      were cultured in agarose. Initially, BMP-2 was used to evaluate the chondrogenic
      potential of the synovial explants under different culturing conditions. Under
      appropriate conditions, the chondrogenic effects of BMP-2, BMP-7, and TGFbeta1
      were then compared. The differentiated tissue was characterized histologically,
      histomorphometrically, immunohistochemically, biochemically, and at the gene
      expression level. RESULTS: BMP-2 induced the chondrogenic differentiation of
      synovial explants in a dose- and time-dependent manner under serum- and
      dexamethasone-free conditions. The expression levels of cartilage-related genes
      increased in a time-dependent manner. BMP-7 was more potent than BMP-2 in
      inducing chondrogenesis, but the properties of the differentiated tissue were
      similar in each case. The type of cartilaginous tissue formed under the influence
      of TGFbeta1 differed in terms of both cell phenotype and gene expression
      profiles. CONCLUSION: The 3 tested members of the TGFbeta superfamily have
      different chondrogenic potentials and induce the formation of different types of
      cartilaginous tissue. To effect the full differentiation of synovial explants
      into a typically hyaline type of articular cartilage, further refinement of the
      stimulation conditions is required. This might be achieved by the simultaneous
      application of several growth factors.

PMID- 17530716
TI  - Toll-like receptors and chondrocytes: the lipopolysaccharide-induced decrease in
      cartilage matrix synthesis is dependent on the presence of toll-like receptor 4
      and antagonized by bone morphogenetic protein 7.
AB  - OBJECTIVE: To assess the presence of Toll-like receptors (TLRs) 1-9 in human
      articular cartilage, and to investigate the effects of lipopolysaccharide (LPS)
      induced activation of TLR-4 on biosynthetic activity and matrix production by
      human articular chondrocytes. METHODS: TLRs 1-9 were assessed in human articular
      cartilage by reverse transcription-polymerase chain reaction (RT-PCR); TLR-4 was
      also analyzed by Western blotting and immunohistochemistry. Articular
      chondrocytes were isolated from human donors and from wild-type or TLR-4(-/-)
      mice. Chondrocyte monolayer cultures were incubated with interleukin-1beta (IL
      1beta) and LPS in the absence or presence of bone morphogenetic protein 7 (BMP-7)
      and IL-1 receptor antagonist (IL-1Ra). Neosynthesis of sulfated
      glycosaminoglycans (sGAG) was measured by (35)S-sulfate incorporation. Endogenous
      gene expression of cartilage markers as well as IL-1beta was examined using RT
      PCR. The involvement of p38 kinase or p44/42 kinase (ERK-1/2) in LPS-mediated TLR
      4 signaling was investigated by immunoblotting, RT-PCR, and sGAG synthesis.
      RESULTS: TLRs 1-9 were found on the messenger RNA (mRNA) level in human articular
      chondrocytes. The presence of TLR-4 was also observed on the protein level. In
      murine and human articular chondrocytes, but not in chondrocytes derived from TLR
      4(-/-) mice, stimulation with LPS resulted in a decrease in total proteoglycan
      synthesis. IL-1beta mRNA expression was increased by TLR-4 activation, whereas
      expression of aggrecan and type II collagen was significantly decreased. The
      presence of BMP-7 and IL-1Ra antagonized the anti-anabolic effects of LPS.
      Blocking of p38, but not ERK-1/2, resulted in inhibition of both LPS-mediated IL
      1beta gene expression and the negative effects of LPS on matrix biosynthesis.
      CONCLUSION: These data demonstrate the presence of TLRs in human articular
      cartilage. The suppressive effects of LPS on cartilage biosynthetic activity are
      dependent on the presence of TLR-4, are governed, at least in part, by an up
      regulation of IL-1beta, and are mediated by p38 kinase. These in vitro data
      indicate an anti-anabolic effect of TLR-4 in articular chondrocytes that may
      hamper cartilage repair in various joint diseases.

PMID- 17530717
TI  - Altered coronary vasomotor function in young patients with systemic lupus
      erythematosus.
AB  - OBJECTIVE: Accelerated atherosclerosis is an important cause of morbidity and
      mortality in patients with systemic lupus erythematosus (SLE). Altered coronary
      microvascular function may act as a marker of changes that predispose to the
      development of significant coronary vascular disease. The purpose of this study
      was to compare coronary flow reserve (CFR) in a group of premenopausal women with
      SLE and a group of age-, sex-, and race-matched healthy control subjects.
      METHODS: Coronary flow velocity in 18 premenopausal women with SLE (mean +/- SD
      age 29.4 +/- 5.9 years) and 19 matched healthy controls (mean +/- SD age 28.2 +/-
      4.3 years) was assessed by transthoracic Doppler echocardiography after an
      overnight fast. The CFR was calculated as the ratio of hyperemic to baseline
      coronary blood flow velocity in the left anterior descending coronary artery.
      Hyperemia was induced by intravenous administration of adenosine triphosphate.
      RESULTS: The mean +/- SD duration of SLE was 8.2 +/- 7.2 years (range 0.25-25
      years), and the mean +/- SD score on the Systemic Lupus Erythematosus Disease
      Activity Index was 11.0 +/- 5.3 (range 4.0-21.0). Adequate recordings of flow
      velocity in the left anterior descending artery under both conditions were
      obtained using an ultrasound procedure in all study subjects. CFR was
      significantly lower in SLE patients as compared with control subjects (mean +/-
      SD 3.4 +/- 0.8 versus 4.5 +/- 0.5; P < 0.0001). CONCLUSION: These findings
      provide evidence that coronary vasomotor function is impaired in patients with
      SLE and support the notion that many of these young patients have subclinical
      coronary artery disease.

PMID- 17530718
TI  - Protection against renal disease in (NZB x NZW)F(1) lupus-prone mice after
      somatic B cell gene vaccination with anti-DNA immunoglobulin consensus peptide.
AB  - OBJECTIVE: Ig molecules contain epitopes that can induce T cell-mediated immune
      responses. B cells can process and present such epitopes and activate T cells.
      The purpose of the present study was to test our hypothesis that T cells that
      recognize an Ig consensus sequence presented by B cells will modulate lupus-like
      disease in mice. METHODS: (NZB x NZW)F(1) (NZB/NZW) lupus mice received somatic B
      cell gene transfer of a DNA plasmid encoding a consensus sequence of T cell
      determinants of murine anti-DNA IgG or control plasmids. Treated animals were
      monitored for the production of antibody, the development of renal disease, and
      the phenotype, number, and function of T cells. RESULTS: Treatment of mice with
      Ig consensus plasmid induced transforming growth factor beta-producing CD8+,CD28-
      T cells that suppressed the antigen-specific stimulation of CD4+ T cells in a
      cell-contact-independent manner, reduced antibody production, retarded the
      development of nephritis, and improved survival. Significantly, adoptive transfer
      of CD8+,CD28- T cells from protected mice into hypergammaglobulinemic NZB/NZW
      mice effectively protected the transferred mice from the development of renal
      disease. CONCLUSION: Gene expression of anti-DNA Ig consensus sequence induces
      immunoregulatory T cells that delay the development of lupus nephritis by
      suppressing hypergammaglobulinemia and renal disease.

PMID- 17530719
TI  - Reduced expression of decay-accelerating factor 1 on CD4+ T cells in murine
      systemic autoimmune disease.
AB  - OBJECTIVE: Deficiency of decay-accelerating factor 1 (termed Daf1 in mice) has
      been shown to exacerbate autoimmunity, and recent studies have suggested that
      this may be explained by Daf1 acting as a regulator of T cell immunity. The aim
      of this study was to determine whether Daf1 expression on T cells is modulated
      during development of autoimmunity in mice. METHODS: To test this hypothesis, we
      examined Daf1 levels in NZB, DBA/2, and B10.S mice before and after induction of
      murine mercury-induced autoimmunity (mHgIA). Daf1 was measured by real-time
      polymerase chain reaction and flow cytometry, and levels of Daf1 were correlated
      with markers of lymphocyte activation and cytokine production. RESULTS:
      Autoimmune-prone NZB mice had low endogenous levels of Daf1 irrespective of the
      induction of mHgIA. Induction of autoimmunity reduced Daf1 expression in mHgIA
      sensitive B10.S mice, particularly on activated/memory (CD44(high)) CD4+ T cells
      that accumulate as a result of exposure to mercury. Murine mercury-induced
      autoimmunity-resistant DBA/2 mice, which fail to accumulate CD44(high) T cells,
      showed no change in Daf1 expression. Modulation of Daf1 expression was found to
      require CD4+ T cell costimulation, since B10.S mice deficient in CD28 were unable
      to down-regulate Daf1 or accumulate activated/memory CD4+ T cells. In B10.S mice
      exposed to mercury, the production of interleukin-4 (IL-4), but not that of IL-2
      or interferon-gamma, in the spleen was associated with CD44(high),Daf1(low),CD4+
      T cells. CONCLUSION: These findings demonstrate that reduction of Daf1 expression
      is closely associated with CD4+ T cell activation and the accumulation of
      CD44(high)(activated/memory),CD4+ T cells in both spontaneous and induced
      systemic autoimmune disease.

PMID- 17530720
TI  - Urinary lipocalin-2 is associated with renal disease activity in human lupus
      nephritis.
AB  - OBJECTIVE: Pathogenic monoclonal anti-double-stranded DNA (anti-dsDNA) antibodies
      up-regulate the expression of lipocalin-2 in glomerular mesangial cells. This
      study was undertaken to investigate whether polyclonal anti-dsDNA antibodies
      promote the local secretion of lipocalin-2 in the kidneys of patients with
      systemic lupus erythematosus (SLE), and whether urinary lipocalin-2 represents a
      marker of kidney involvement in SLE. METHODS: Hispanic, African American, and
      white patients with SLE and normal healthy control subjects from affiliated
      hospitals of the Albert Einstein College of Medicine were recruited for this
      cross-sectional study. Patients were classified based on the presence of active
      renal disease according to the SLE Disease Activity Index (SLEDAI). Correlations
      of clinical and laboratory data with urinary and serum levels of lipocalin-2 were
      assessed. RESULTS: Among SLE patients, urinary lipocalin-2 levels were
      significantly higher in those with lupus nephritis (LN) (median 17.1 ng/mg
      creatinine, interquartile range [IQR] 10.3-45.4; n = 32) than in those without LN
      (median 11.2 ng/mg creatinine, IQR 3.1-20.3; n = 38) (P = 0.023). Compared with
      the values in normal controls (median 4 ng/ml, IQR 0-11.1; n = 14), urinary
      levels of lipocalin-2 in SLE patients were significantly higher (non-normalized
      median 19.3 ng/ml, IQR 8-34.2) (P = 0.004). The presence of lipocalin-2 in the
      urine of patients with LN correlated significantly with the renal SLEDAI score (r
      = 0.452, P = 0.009), but not with extrarenal disease activity. CONCLUSION: The
      high prevalence of LN in SLE patients and the prognostic significance of kidney
      disease support the need for identifying early biomarkers to assess the risk of
      nephritis development and for following up patients with established disease.
      These findings indicate that urinary lipocalin-2 is a potential marker of the
      presence and severity of renal involvement in adult patients with SLE.

PMID- 17530721
TI  - Specific gene expression profiles in systemic juvenile idiopathic arthritis.
AB  - OBJECTIVE: Patients with systemic juvenile idiopathic arthritis (JIA) have
      arthritis, quotidian fevers, and other extraarticular features. This disease
      often remains severe and debilitating. The purpose of this study was to compare
      gene expression profiles in peripheral blood mononuclear cells (PBMCs) from
      patients with active and inactive systemic JIA to define and better understand
      the cause of active disease. METHODS: Gene expression profiles of PBMCs were
      determined in cells from 9 patients with active systemic JIA and 8 patients with
      inactive systemic JIA. Unsupervised clustering and significance analysis were
      performed. We compared the systemic JIA profile with data from patients with
      polyarticular JIA, chronic infantile neurologic, cutaneous, articular syndrome,
      Kawasaki disease, and systemic lupus erythematosus to identify disease-specific
      genes. Quantitative reverse transcription-polymerase chain reaction of selected
      genes was performed on negatively selected B cells, T cells, and monocytes.
      RESULTS: Unsupervised clustering of expressed genes resulted in 2 groups that
      corresponded to the clinical status of the patients (active and inactive disease)
      and was independent of their medications. A total of 286 genes were identified as
      significantly up-regulated in patients with active disease and 86% of them were
      specific to systemic JIA. Interleukin-6 (IL-6) was expressed in monocytes and B
      cells, IL-10 in monocytes, and suppressor of cytokine signaling 3 in monocytes
      and T cells from patients with active disease. CONCLUSION: Gene expression
      profiles in PBMCs identified disease-specific genes in patients with systemic
      JIA. Cell type analyses should allow further insight into the mechanisms of the
      disease.

PMID- 17530722
TI  - Prevalence and etiology of low bone mineral density in juvenile systemic lupus
      erythematosus.
AB  - OBJECTIVE: Studies of adults with systemic lupus erythematosus (SLE) have
      frequently demonstrated the presence of decreased bone mineral density (BMD).
      However, there have been few investigations in pediatric patients to date. This
      study was undertaken to determine the prevalence of low BMD in patients with
      juvenile SLE and to identify associated risk factors. METHODS: We studied 64
      consecutive patients with juvenile SLE in whom routine dual x-ray absorptiometry
      (DXA) scanning was performed. Lumbar spine osteopenia was defined as a BMD Z
      score of < -1 and > or = -2.5, and osteoporosis as a BMD Z score of < -2.5.
      Decreased hip BMD was defined as a value of < 80%. Data on disease activity,
      quality of life, disease-related damage, sex, ethnicity, body mass index, age at
      diagnosis, age at DXA, medication use and duration, clinical features, and
      puberty status were collected at the time of DXA. RESULTS: Lumbar spine
      osteopenia was seen in 24 patients (37.5%) and osteoporosis in 13 (20.3%).
      Decreased hip BMD was present in 12 patients (18.8%). By univariate analysis,
      osteopenia was significantly correlated with age, disease duration, duration of
      corticosteroid use, cumulative corticosteroid dose, azathioprine use,
      cyclophosphamide use, lupus nephritis, and damage. Two additional variables,
      mycophenolate mofetil use and class III-IV nephritis, were associated with
      osteoporosis. Abnormal hip BMD was associated with disease duration, duration of
      corticosteroid use, and cumulative corticosteroid dose. By multivariate analysis,
      only disease duration remained in the model for osteoporosis and abnormal hip
      BMD, while cumulative corticosteroid dose was the variable associated with
      osteopenia. CONCLUSION: These results indicate that osteopenia and osteoporosis
      are common in juvenile SLE and are associated more closely with increased disease
      duration than with cumulative corticosteroid dose.

PMID- 17530723
TI  - Epidemiology of juvenile idiopathic arthritis in a multiethnic cohort: ethnicity
      as a risk factor.
AB  - OBJECTIVE: To study the influence of ethnicity on the risk of developing juvenile
      idiopathic arthritis (JIA) in a multiethnic community of patients with
      unrestricted access to health care. METHODS: A questionnaire on ethnicity was
      distributed to all patients with JIA being followed up at the Hospital for Sick
      Children in Toronto, Ontario, Canada. Of 1,082 patients, 859 (79.4%) responded to
      the questionnaire. To calculate the relative risk (RR) of developing JIA in this
      study cohort, the results were compared with data from the age-matched general
      population of the Toronto metropolitan area (TMA) as provided in the 2001 census
      from Statistics Canada. RESULTS: European descent was reported by 69.7% of the
      patients with JIA compared with a frequency of 54.7% in the TMA general
      population, whereas a statistically significantly lower than expected percentage
      of the patients with JIA reported having black, Asian, or Indian subcontinent
      origin. Children of European origin had a higher RR for developing any of the JIA
      subtypes except polyarticular rheumatoid factor (RF)-positive JIA, and were
      particularly more likely to develop the extended oligoarticular and psoriatic
      subtypes. A higher frequency of enthesitis-related JIA was observed among
      patients of Asian origin, while those of black origin or native North American
      origin were more likely to develop polyarticular RF-positive JIA. CONCLUSION: In
      this multiethnic cohort, European descent was associated with a significantly
      increased risk of developing JIA, and the distribution of JIA subtypes differed
      significantly across ethnic groups.

PMID- 17530724
TI  - [(NHC)AuI]-catalyzed formation of conjugated enones and enals: an experimental
      and computational study.
AB  - The [(NHC)AuI]-catalyzed (NHC=N-heterocyclic carbene) formation of alpha,beta
      unsaturated carbonyl compounds (enones and enals) from propargylic acetates is
      described. The reactions occur at 60 degrees C in 8 h in the presence of an
      equimolar mixture of [(NHC)AuCl] and AgSbF6 and produce conjugated enones and
      enals in high yields. Optimization studies revealed that the reaction is
      sensitive to the solvent, the NHC, and, to a lesser extent, to the silver salt
      employed, leading to the use of [(ItBu)AuCl]/AgSbF6 in THF as an efficient
      catalytic system. This transformation proved to have a broad scope, enabling the
      stereoselective formation of (E)-enones and -enals with great structural
      diversity. The effect of substitution at the propargylic and acetylenic positions
      has been investigated, as well as the effect of aryl substitution on the
      formation of cinnamyl ketones. The presence or absence of water in the reaction
      mixture was found to be crucial. From the same phenylpropargyl acetates,
      anhydrous conditions led to the formation of indene compounds via a tandem [3,3]
      sigmatropic rearrangement/intramolecular hydroarylation process, whereas simply
      adding water to the reaction mixture produced enone derivatives cleanly. Several
      mechanistic hypotheses, including the hydrolysis of an allenol ester intermediate
      and SN2' addition of water, were examined to gain an insight into this
      transformation. Mechanistic investigations and computational studies support
      [(NHC)AuOH], produced in situ from [(NHC)AuSbF6] and H2O, instead of cationic
      [(NHC)AuSbF6] as the catalytically active species. Based on DFT calculations
      performed at the B3LYP level of theory, a full catalytic cycle featuring an
      unprecedented transfer of the OH moiety bound to the gold center to the C[triple
      chemical bond]C bond leading to the formation of a gold-allenolate is proposed.

PMID- 17530725
TI  - Malaria chemotherapeutics part I: History of antimalarial drug development,
      currently used therapeutics, and drugs in clinical development.
AB  - Since ancient times, humankind has had to struggle against the persistent
      onslaught of pathogenic microorganisms. Nowadays, malaria is still the most
      important infectious disease worldwide. Considerable success in gaining control
      over malaria was achieved in the 1950s and 60s through landscaping measures,
      vector control with the insecticide DDT, and the widespread administration of
      chloroquine, the most important antimalarial agent ever. In the late 1960s, the
      final victory over malaria was believed to be within reach. However, the
      parasites could not be eradicated because they developed resistance against the
      most widely used and affordable drugs of that time. Today, cases of malaria
      infections are on the rise and have reached record numbers. This review gives a
      short description of the malaria disease, briefly addresses the history of
      antimalarial drug development, and focuses on drugs currently available for
      malaria therapy. The present knowledge regarding their mode of action and the
      mechanisms of resistance are explained, as are the attempts made by numerous
      research groups to overcome the resistance problem within classes of existing
      drugs and in some novel classes. Finally, this review covers all classes of
      antimalarials for which at least one drug candidate is in clinical development.
      Antimalarial agents that are solely in early development stages will be addressed
      in a separate review.

PMID- 17530726
TI  - Paclitaxel and docetaxel resistance: molecular mechanisms and development of new
      generation taxanes.
AB  - Taxanes represent one of the most promising classes of anticancer agents.
      Unfortunately, their clinical success has been limited by the insurgence of
      cellular resistance, mainly mediated by the expression of the MDR phenotype or by
      microtubule alterations. However, the remarkable relevance of paclitaxel and
      docetaxel in clinical oncology stimulated intensive efforts in the last decade to
      identify new derivatives endowed with improved activities towards resistant tumor
      cells, resulting in a huge number of novel natural and synthetic taxanes. Among
      them, several structurally different derivatives were found to exhibit a
      promising behavior against the MDR phenotype in terms of either MDR inhibiting
      properties, or enhanced cytotoxicity compared to parental drugs, or both. On the
      other hand, only in more recent years have the first taxanes retaining activity
      against resistant cancer cells bearing alterations of the tubulin/microtubule
      system emerged. This review describes the main molecular mechanisms of resistance
      to paclitaxel and docetaxel identified so far, focusing on the advances achieved
      in the development of new taxanes potentially useful for the treatment of
      resistant tumors.

PMID- 17530727
TI  - Predicting and tuning physicochemical properties in lead optimization: amine
      basicities.
AB  - This review describes simple and useful concepts for predicting and tuning the
      pK(a) values of basic amine centers, a crucial step in the optimization of
      physical and ADME properties of many lead structures in drug-discovery research.
      The article starts with a case study of tricyclic thrombin inhibitors featuring a
      tertiary amine center with pK(a) values that can be tuned over a wide range, from
      the usual value of around 10 to below 2 by (remote) neighboring functionalities
      commonly encountered in medicinal chemistry. Next, the changes in pK(a) of
      acyclic and cyclic amines upon substitution by fluorine, oxygen, nitrogen, and
      sulfur functionalities, as well as carbonyl and carboxyl derivatives are
      systematically analyzed, leading to the derivation of simple rules for pK(a)
      prediction. Electronic and stereoelectronic effects in cyclic amines are
      discussed, and the emerging computational methods for pK(a) predictions are
      briefly surveyed. The rules for tuning amine basicities should not only be of
      interest in drug-discovery research, but also to the development of new crop
      protection agents, new amine ligands for organometallic complexes, and in
      particular, to the growing field of amine-based organocatalysis.

PMID- 17530728
TI  - Chemical medicine: novel 10-substituted cytisine derivatives with increased
      selectivity for alpha4beta2 nicotinic acetylcholine receptors.

PMID- 17530729
TI  - Synthesis and evaluation of 3-phenylpyrazolo[3,4-d]pyrimidine-peptide conjugates
      as Src kinase inhibitors.
AB  - 3-Phenylpyrazolo[3,4-d]pyrimidine (PhPP) derivatives substituted with an alkyl or
      aryl carboxylic acid at the N1-endocyclic amine, such as PhPP-CH(2)COOH
      (IC(50)=250 microM), and peptides Ac-CIYKYY (IC(50)=400 microM) and Ac-YIYGSFK
      (IC(50)=570 microM) were weak inhibitors of polyE(4)Y phosphorylation by active c
      Src. A series of PhPP-peptide conjugates were synthesized using PhPP as an ATP
      mimic and CIYKYY or YIYGSFK as a peptide substrate to improve the inhibitory
      potency against active c-Src kinase. PhPP derivatives were attached to the N
      terminus or the side chain of amino acids in the peptide template. Two N-terminal
      substituted conjugates, PhPP-CH(2)CO-CIYKYY (IC(50)=0.38 microM) and PhPP-CH(2)CO
      YIYGSFK (IC(50)=2.7 microM), inhibited the polyE(4)Y phosphorylation by active c
      Src significantly higher than that of the parent compounds. The conjugation of
      PhPP with the peptides produced a synergistic inhibition effect possibly through
      creation of favorable interactions between the conjugate and the kinase domain as
      shown by molecular modeling studies.

PMID- 17530730
TI  - Ab initio static and molecular dynamics study of 4-styrylpyridine.
AB  - We report an in-depth theoretical study of 4-styrylpyridine in its singlet S(0)
      ground state. The geometries and the relative stabilities of the trans and cis
      isomers were investigated within density functional theory (DFT) as well as
      within Hartree-Fock (HF), second-order Moller-Plesset (MP2), and coupled cluster
      (CC) theories. The DFT calculations were performed using the B3LYP and PBE
      functionals, with basis sets of different qualities, and gave results that are
      very consistent with each other. The molecular structure is thus predicted to be
      planar at the energy minimum, which is associated with the trans conformation,
      and to become markedly twisted at the minimum of higher energy, which is
      associated with the cis conformation. The results of the calculations performed
      with the post-HF methods approach those obtained with the DFT methods, provided
      that the level of treatment of the electronic correlation is high enough and that
      sufficiently flexible basis sets are used. Calculations carried out within DFT
      also allowed the determination of the geometry and the energy of the molecule at
      the biradicaloid transition state associated with the thermal cis=trans
      isomerization and at the transition states associated with the enantiomerization
      of the cis isomer and with the rotations of the pyridinyl and phenyl groups in
      the trans and cis isomers. Car-Parrinello molecular dynamics simulations were
      also performed at 50, 150, and 300 K using the PBE functional. The studies
      allowed us to evidence the highly flexible nature of the molecule in both
      conformations. In particular, the trans isomer was found to exist mainly in a
      nonplanar form at finite temperatures, while the rotation of the pyridinyl ring
      in the cis isomer was incidentally observed to take place within approximately 1
      ps during the simulation carried out at 150 K on this isomer.

PMID- 17530731
TI  - Divergent synthesis of multifunctional molecular probes to elucidate the enzyme
      specificity of dipeptidic gamma-secretase inhibitors.
AB  - Divergent synthesis of multifunctional molecular probes based on caprolactam
      derived dipeptidic gamma-secretase inhibitors (GSIs), Compound E (CE) and
      LY411575 analogue (DBZ), was efficiently accomplished by means of Cu(I)-catalyzed
      azide/alkyne fusion reaction. Photoaffinity labeling experiments using these
      derivatives coupled to photoactivatable and biotin moieties provided direct
      evidence that the molecular targets of CE and DBZ are the N-terminal fragment of
      presenilin 1 within the gamma-secretase complex. Moreover, these photoprobes
      directly targeted signal peptide peptidase. These data suggest that the divergent
      synthesis of molecular probes has been successfully applied to characterize the
      interaction of GSIs with their molecular targets and define the structural
      requirements for inhibitor binding to intramembrane-cleaving proteases.

PMID- 17530732
TI  - Thyronamines inhibit plasma membrane and vesicular monoamine transport.
AB  - Thyroid hormone has long been known to have important transcriptional regulatory
      activities. Recently, however, the presence of endogenous derivatives of thyroid
      hormone, thyronamines, has been reported in various mammalian tissues. These
      derivatives have potent in vitro activity with a class of orphan G-protein
      coupled receptors, the trace amine-associated receptors, and profound in vivo
      effects when administered to mice. We report here a novel neuromodulatory role
      for thyronamines. In synaptosomal preparations and heterologous expression
      systems, thyronamines act as specific dopamine and norepinephrine reuptake
      inhibitors. Thyronamines also inhibit the transport of monoamines into synaptic
      vesicles. These observations expand the nontranscriptional role of thyroid
      hormone derivatives and may help to explain the pharmacological effects of
      thyronamines in vivo.

PMID- 17530733
TI  - Mitomycin-DNA adducts induce p53-dependent and p53-independent cell death
      pathways.
AB  - 10-Decarbamoyl-mitomycin C (DMC), a mitomycin C (MC) derivative, generates an
      array of DNA monoadducts and interstrand cross-links stereoisomeric to those that
      are generated by MC. DMC was previously shown in our laboratory to exceed the
      cytotoxicity of MC in a human leukemia cell line that lacks a functional p53
      pathway (K562). However, the molecular signal transduction pathway activated by
      DMCDNA adducts has not been investigated. In this study, we have compared
      molecular targets associated with signaling pathways activated by DMC and MC in
      several human cancer cell lines. In cell lines lacking wild-type p53, DMC was
      reproducibly more cytotoxic than MC, but it generated barely detectable signal
      transduction markers associated with apoptotic death. Strikingly, DMCs increased
      cytotoxicity was not associated with an increase in DNA double-strand breaks but
      was associated with early poly(ADP-ribose) polymerase (PARP) activation and Chk1
      kinase depletion. Alkylating agents can induce increased PARP activity associated
      with programmed necrosis, and the biological activity of DMC in p53-null cell
      lines fits this paradigm. In cell lines with a functional p53 pathway, both MC
      and DMC induced apoptosis. In the presence of p53, both MC and DMC activate
      procaspases; however, the spectrum of procaspases involved differs for the two
      drugs, as does induction of p73. These studies suggest that in the absence of
      p53, signaling to molecular targets in cell death can shift in response to
      different DNA adduct structures to induce non-apoptotic cell death.

PMID- 17530734
TI  - High-throughput, microarray-based synthesis of natural product analogues via in
      vitro metabolic pathway construction.
AB  - The generation of biological diversity by engineering the biosynthetic gene
      assembly of metabolic pathway enzymes has led to a wide range of "unnatural"
      variants of natural products. However, current biosynthetic techniques do not
      allow the rapid manipulation of pathway components and are often fundamentally
      limited by the compatibility of new pathways, their gene expression, and the
      resulting biosynthetic products and pathway intermediates with cell growth and
      function. To overcome these limitations, we have developed an entirely in vitro
      approach to synthesize analogues of natural products in high throughput. Using
      several type III polyketide synthases (PKS) together with oxidative post-PKS
      tailoring enzymes, we performed 192 individual and multienzymatic reactions on a
      single glass microarray. Subsequent array-based screening with a human tyrosine
      kinase led to the identification of three compounds that acted as modest
      inhibitors in the low-micromolar range. This approach, therefore, enables the
      rapid construction of analogues of natural products as potential pharmaceutical
      lead compounds.

PMID- 17530735
TI  - Combinatorial modulation of protein prenylation.
AB  - The cell has >60 different farnesylated proteins. Many critically important
      signal transduction proteins are post-translationally modified with attachment of
      a farnesyl isoprenoid catalyzed by protein farnesyltransferase (FTase). Recently,
      it has been shown that farnesyl diphosphate (FPP) analogues can alter the peptide
      substrate specificity of FTase. We have used combinatorial screening of FPP
      analogues and peptide substrates to identify patterns in FTase substrate
      selectivity. Each FPP analogue displays a unique pattern of substrate reactivity
      with the tested peptides; FTase efficiently catalyzes the transfer of an FPP
      analogue selectively to one peptide and not another. Furthermore, we have
      demonstrated that these analogues can enter cells and be incorporated into
      proteins. These FPP analogues could serve as selective tools to examine the role
      prenylation plays in individual protein function.

PMID- 17530736
TI  - Architectural design, interior decoration, and three-dimensional plumbing en
      route to multifunctional nanoarchitectures.
AB  - Ultraporous aperiodic solids, such as aerogels and ambigels, are sol-gel-derived
      equivalents of architectures. The walls are defined by the nanoscopic, covalently
      bonded solid network of the gel. The vast open, interconnected space
      characteristic of a building is represented by the three-dimensionally continuous
      nanoscopic pore network. We discuss how an architectural construct serves as a
      powerful metaphor that guides the chemist in the design of aerogel-like
      nanoarchitectures and in their physical and chemical transformation into
      multifunctional objects that yield high performance for rate-critical
      applications.

PMID- 17530737
TI  - Profiling of organic acids during fermentation by ultraperformance liquid
      chromatography-tandem mass spectrometry.
AB  - A method has been developed for rapid quantification of organic acids using
      ultraperformance liquid chromatography/electrospray-tandem mass spectrometry
      (UPLC/ESI-MS-MS) to monitor the metabolism of 10 organic acids during microbial
      fermentation. Because comprehensive chromatographic separation is not required,
      analysis time is less than traditional ion chromatography assays, with complete
      organic acid analyses by UPLC/ESI-MS-MS being achieved in less than 3 min.
      Quantification is accomplished using nine isotopically labeled organic acids as
      internal standards. Intrasample precisions for organic acid measurements in
      fermentation supernatants using this method average 8.9% (RSD). Calibration
      curves are linear over the range of 0.06-100 microg/mL, and detection limits are
      estimated at 0.06-1 microg/mL. This method has the potential to demonstrate
      correlation of organic acid consumption and production by microorganisms with
      observed growth profiles, novel media formulations, and cellular growth events.
      Data visualization software has been used to profile organic acid levels during
      fermentation and correlate these profiles to nutrient supplementation protocols
      employed during microbial production. The potential use of this capability in
      computational modeling and simulation of microbial metabolism to accelerate the
      bioprocess development cycle is recognized.

PMID- 17530738
TI  - Scanning electrochemical microscopy. 57. SECM tip voltammetry at different
      substrate potentials under quasi-steady-state and steady-state conditions.
AB  - We discuss SECM tip voltammetry, where a UME tip is held above a conductive
      substrate within about a tip radius and a tip voltammogram is recorded as its
      potential is slowly scanned while the substrate is held at a fixed potential.
      When the potential of the substrate is changed, the series of steady-state tip
      voltammograms provide information about the reactants and products. When the
      potential of the substrate, ES, is set so that the reaction at the substrate is
      opposite to that at the tip (the usual SECM conditions), a total positive
      feedback (tpf) tip voltammogram is recorded. When the substrate potential is set
      to values where the reaction at the substrate is the same as that occurring on
      the tip, the tip is shielded from the species in the bulk solution. Depending
      upon the substrate potential, this can cause total shielding (ts) or a
      voltammogram that is the result of partial feedback/partial shielding (pf-ps).
      The result is a series of tip voltammograms that are characterized by tpf, pf-ps,
      or ts, depending upon ES. Experimental tip voltammograms resulting from the
      reversible reduction of TCNQ and oxidation of ferrocene in MeCN are reported.
      These are compared with those from simulations and approximate equations
      developed to describe the features of the tip voltammograms generated under tpf,
      ts, or pf-ps conditions. The effect of the diffusion coefficient ratio on the
      ability of the UME tip to reach a true steady state is also addressed and
      possible applications, e.g., obtaining information about the reversibility of an
      electrochemical reaction, the product of an electrochemical reaction, the
      stability of that product, or the diffusion coefficients of the electroactive
      species, are discussed.

PMID- 17530739
TI  - Microchip for combining gas chromatography or capillary liquid chromatography
      with atmospheric pressure photoionization-mass spectrometry.
AB  - We present a microfabricated nebulizer chip for combining atmospheric pressure
      photoionization-mass spectrometry (APPI-MS) with gas chromatography (GC) or
      capillary liquid chromatography (capLC). The chip consists of a silicon plate and
      a glass plate or two glass plates. The chip includes a sample inlet channel,
      auxiliary gas and dopant inlet, vaporizer channel, nozzle, and platinum heater.
      The sample eluted from the capLC or GC is mixed with auxiliary gas and dopant
      (toluene) in the heated vaporizer. The chip forms a confined jet of the sample
      vapor, which is photoionized as it exits the chip. The analytical performance of
      GC- and capLC-microchip APPI-MS was evaluated with some polycyclic aromatic
      hydrocarbons, amphetamines, and steroids. The GC-muAPPI-MS method provides high
      sensitivity down to 0.8 fmol, repeatability (RSD = 7.5-14%), and linearity (r =
      0.9952-0.9987). The capLC-muAPPI-MS method shows high sensitivity down to 1 fmol,
      good repeatability (RSD = 3.6-8.1%), and linearity (r = 0.9989-0.9992).

PMID- 17530740
TI  - Immobilization of malarial (Plasmodium falciparum) dihydrofolate reductase for
      the selection of tight-binding inhibitors from combinatorial library.
AB  - A simple procedure for selection of tight-binding inhibitors of mutant
      dihydrofolate reductases from Plasmodium falciparum (PfDHFRs) based on
      preferential binding to the enzyme immobilized on a Sepharose column has been
      described. PfDHFRs with a cysteine residue at the C-terminal have been prepared
      in order to immobilize to a thiopropyl-Sepharose gel via S-S linkage. The amount
      of immobilized DHFRs was estimated to be 4-5 mg/g of dried gel, and the
      activities of bound DHFRs were comparable to that of free enzymes. The prepared
      immobilized enzyme has been used for the selection of tight-binding inhibitors
      from combinatorial libraries, based on the affinities of each ligand with the
      enzyme. Free ligands were then identified and analyzed quantitatively by high
      performance liquid chromatography-mass spectrometry, and the components with high
      binding affinity of the library could thus be realized. Results could be
      confirmed by quantitative analysis of the bound ligands released from the enzyme
      by guanidine hydrochloride treatment.

PMID- 17530741
TI  - Augmenting spectroscopic imaging for analyses of samples with complex surface
      topographies.
AB  - Spectroscopic imaging has become a widely used tool for analyses of heterogeneous
      samples. Focal plane array detectors are incorporated into spectrometers that
      acquire a large number of spectra from different sample locations in parallel.
      This sensing technique facilitates analyses of spatial distributions of chemical
      information in an X-Y plane at high time resolution. In many cases, chemical
      reactions proceed in three spatial dimensions (X-Y-Z) and require the acquisition
      of spectroscopic information in an X-Y plane plus topographic (Z-dimension)
      information. However, capturing two-dimensional (2D, i.e., X-Y) images from three
      dimensional (3D, i.e., X-Y-Z) samples inherently loses Z-dimension information.
      This technical note describes an augmented spectroscopic imager that gains both
      types of data, i.e., spatially resolved spectroscopic information and topography.
      For the latter purpose, a regular light pattern is generated and projected onto a
      sample. Due to its 3D topography, this light pattern is distorted. After
      extracting these distortions, the topography can be determined since the height
      structure is encoded in the light pattern. Because topographic probing must not
      affect infrared measurements, different wavelength ranges are used. Here
      spectroscopic information is acquired in the mid-IR while the light pattern
      probing the topography is generated in the visible. For relating distortions to
      physical height structures, the setup needs to be calibrated. For this purpose,
      calibration objects of known dimensions have been manufactured onto which the
      light pattern is projected. Determining distortions introduced by objects of
      known height derives a transform from distortions to topographies. Due to
      mechanical restrictions, the light pattern can only achieve a certain spatial
      resolution. In order to enhance the spatial resolution the topography is probed
      with, scanning the light pattern in X- and Y-direction is proposed.

PMID- 17530742
TI  - A new look at radicals in cigarette smoke.
AB  - Radicals in cigarette smoke have been proposed to contribute to the harm caused
      by cigarette smoking. For the first time, using HPLC and high-resolution mass
      spectrometry analysis of stable radical adducts, we have identified specific
      radical species in cigarette smoke: 7 acyl and 11 alkylaminocarbonyl radicals.
      Their combined abundance measured in fresh whole smoke from a single 2R4F
      cigarette is approximately 225 nmol (1.4 x 10(17) radicals). The fiberglass
      Cambridge filter pad conventionally employed to separate the gas phase from
      mainstream smoke was found to reduce the apparent yield of these radicals,
      introducing artifacts of measurement. The long-accepted steady-state mechanism
      for the formation of carbon-centered radicals in cigarette smoke involving NO2
      chemistry cannot account for these newly identified radicals, and it does not in
      general appear to be a major source of carbon-centered radicals in fresh
      mainstream cigarette smoke. Consequently, we suggest that the precise nature of
      radicals in cigarette smoke warrants reexamination.

PMID- 17530743
TI  - Aptamer-functionalized gold nanoparticles for turn-on light switch detection of
      platelet-derived growth factor.
AB  - An aptamer modified gold nanoparticles (Apt-AuNPs) based molecular light
      switching sensor has been demonstrated for the analysis of breast cancer markers
      (platelet-derived growth factors (PDGFs) and their receptors) in homogeneous
      solutions. The PDGF binding aptamer has a unique structure with triple-helix
      conformation that allows N,N-dimethyl-2,7-diazapyrenium dication (DMDAP) and PDGF
      bindings. The fluorescence of DMDAP is almost completely quenched by Apt-AuNPs
      when it intercalates with the aptamers. Owing to high magnitudes of increases (up
      to 40-fold) in the turn-on fluorescence signals of DMDAP/Apt-AuNP upon PDGFs
      binding, the approach is highly sensitive for the detection of PDGFs. The
      DMDAP/Apt-AuNP probe specifically and sensitively detected PDGFs under optimal
      concentrations of salts and DMDAP. We also demonstrated that the Apt-AuNPs are
      effective selectors for enrichment of PDGF-AA from large-volume samples. The
      approach allows detection of PDGF-AA at a concentration down to 8 pM, showing
      better sensitivity than other signal aptamers. By conducting a competitive assay,
      we demonstrated the determination of PDGF receptor-alpha with LOD of 0.25 nM when
      using the DMDAP/Apt-AuNP as a probe.

PMID- 17530744
TI  - Restricted geometry optimization: a different way to estimate stabilization
      energies for aromatic molecules of various types.
AB  - At RHF, MPn, and DFT levels, a procedure of geometry optimization under the
      restrictions of pi-orbital interactions (GOR) was developed, thus providing a
      conjugated molecule with the following two types of localized reference
      geometries: a "GL" geometry where all double bonds are localized, and n different
      "GE-n" geometries, in each of which only two double bonds were permitted to
      conjugate. Interestingly, the molecular energy differences between the
      corresponding pairs of GE-n and GL geometries were found to be additive in each
      of the acyclic polyenes, and these were not additive for benzene. As a result, an
      extra stabilization energy (ESE) value of -39.0 kcal/mol was found in benzene.
      Afterward, GOR was applied to benzene- and furan-like species, strained aromatic
      molecules, and substituted benzenes, and the calculated ESEs for these molecules
      were found to be in reasonable ranges. The GOR can isolate a specific group from
      other groups, and it has several special functions. First, with regard to the
      substituent effect, the ESE difference between substituted benzene and benzene
      can be partitioned into conjugative and inductive parts. Second, the behavior of
      strained aromatic molecules can be ascertained from the roles of their resonance
      interactions, strained-induced bond localization (SIBL), and inductive effects,
      indicating that it is resonance interactions, rather than SIBL, which are
      responsible for localizing double bonds. Emphatically, it is the GL and GE-n
      geometries of aromatic molecules, rather than nonaromatic compounds, which can be
      used as the reference structures for calculating ESE. Particularly, these
      localized geometries are no longer arbitrary.

PMID- 17530745
TI  - Electron density analyses of opioids: a comparative study.
AB  - The electron densities of five morphine related molecules (codeine,
      diprenorphine, naltrexone in the neutral and protonated states, and
      dextromethorphan) were determined from high-resolution X-ray diffraction
      experiments (Mo Kalpha and synchrotron primary radiation) at low temperature and
      CCD area detection techniques. Bond topological analyses were applied, and a
      partitioning of the molecules into atomic regions making use of Bader's zero flux
      surfaces yielded atomic volumes and charges. The obtained atom and bonding
      properties were compared to the results of a previous experimental study of
      morphine and to theoretical calculations. Experimental and theoretical properties
      for all chemically equivalent bonds agree within an uncertainty range as is
      otherwise seen for different theoretical calculations. Hence, the transferability
      of chemically equivalent submolecular properties, being a key issue of the atoms
      in molecules (AIM) theory, has been verified experimentally in this class of
      chemically related molecules. On the other hand, topological differences could
      clearly be verified in regions with different chemical environments. Electron
      density differences between the two forms of naltrexone were examined and made
      visible in an extended region around the nitrogen atom which is once in a neutral
      state and once in a positively charged state.

PMID- 17530746
TI  - Structural preferences, argon nanocoating, and dimerization of n-alkanols as
      revealed by OH stretching spectroscopy in supersonic jets.
AB  - n-Alkanols can occur in a multitude of energetically competitive conformational
      states. Using the OH stretching vibration as an infrared and Raman spectroscopic
      sensor in supersonic jet expansions, the torsional preferences around the Calpha
      O and Cbeta-Calpha bonds are probed for n-propanol through n-hexanol. Raman
      detection is more powerful for isolated monomers, whereas IR spectroscopy is more
      sensitive for molecular complexes. The subtle IR vibrational shift induced by the
      nanocoating of n-alcohols with Ar atoms is shown to alternate with chain length.
      A large number of alcohol dimer absorptions is observed and subjected to
      collisional relaxation and nanocoating conditions. Essential features of the
      dimer spectra are modeled successfully by a simple force field approach.
      Exploratory quantum chemical calculations up to the MP2/aug-cc-pvqz level
      encourage a rigorous theoretical study of the subtle conformational aspects in
      monomers and possibly also in dimers of linear alcohols.

PMID- 17530747
TI  - The Hartree-Fock-Heitler-London method, III: Correlated diatomic hydrides.
AB  - In a recently proposed model, called Hartree-Fock-Heitler-London (HF-HL)
      (Corongiu, G. J. Phys. Chem. A 2006, 110, 11584), the molecular wave function was
      variationally obtained by merging two traditional models, Hartree-Fock (HF) and
      Heitler-London (HL). In the new method, the non-dynamical correlation energy
      which includes state avoided crossing-is explicitly calculated with a few
      configurations. In this work the dynamical correlation energy for diatomic
      hydrides of the first and second period is computed both ab initio, via short MC
      HF and MC-HL expansions-including ionic and excited covalent structures-and
      semiempirically, using the Coulomb hole algorithm, a density functional proposed
      by Clementi in the early 1960s. The Coulomb Hole correction is applied to HF and
      HF-HL functions, and, departing from tradition, also to HL functions. Few ab
      initio HF-HL configurations with inclusion of ionic structures yield reasonable
      binding energies not only for the hydrides considered but also for the van der
      Waals HeH molecule. The computed binding energies (in kcal/mol) from HF-HL
      functions corrected with the Coulomb hole functional are as follows: 109.48
      (109.48) for H2[1Sigma+g]; 0.01 (0.01) for HeH [2Sigma+]; 59.22 (58.00) for LiH
      [1Sigma+], 49.55 (49.83) for BeH [2Sigma+], 86.77 (84.1) for BH [1Sigma+], 82.65
      (83.9) for CH [2Pi], 81.57 (80.5) for NH [3Sigma-], 107.18 (106.6) for OH [2Pi],
      and 140.91 (141.5) for HF [1Sigma+]; experimental values are given in
      parentheses. The computed total energies are in good agreement with exact
      nonrelativistic values. The combined availability of the correlation and binding
      energies from HF, HL, and HF-HL models allows a novel analyses on the hydrides
      chemical bond, in agreement with accepted physical chemistry concept derived from
      MO and VB theories.

PMID- 17530748
TI  - Experimental and computational thermochemical study of 2- and 3-thiopheneacetic
      acid methyl esters.
AB  - Thiophene-based compounds have widespread use in modern drug design,
      biodiagnostics, electronic and optoelectronic devices, and conductive polymers.
      The present study reports an experimental and computational thermochemical study
      on the relative stabilities of 2- and 3-thiopheneacetic acid methyl esters. The
      enthalpies of combustion and vaporization were measured by a rotating-bomb
      combustion calorimeter, Calvet microcalorimetry, and correlation gas
      chromatography, and the gas-phase enthalpies of formation at T=298.15 K were
      determined. Standard ab initio molecular orbital calculations at the G3 level
      were performed, and a theoretical study of the molecular and electronic structure
      of the compounds studied was carried out. Calculated enthalpies of formation,
      using atomization and isodesmic reactions are in very good agreement with the
      experimental results.

PMID- 17530749
TI  - General method for reducing adaptive laser pulse-shaping experiments to a single
      control variable.
AB  - Adaptive laser pulse shaping has proven to be expeditious for discovering laser
      pulse shapes capable of manipulating complex systems. However, if adaptive
      control is to be a valuable interrogative technique that informs physical and
      chemical research, methods that make it possible to infer mechanistic information
      from experimental results must be developed. Here, we demonstrate multivariate
      statistical analysis to extract a single control variable from results of a 137
      parameter adaptive laser pulse-shaping optimization of multiphoton electronic
      excitation in a ruthenium(II) coordination complex in solution. We show that this
      single variable can be used to linearly manipulate the observed fitness, which is
      determined by the ratio of molecular emission to second harmonic generation of
      the laser pulse, over the range explored during the adaptive optimization.
      Further, manipulation of this variable reveals the latent control mechanism. For
      this system, that mechanism entails focusing the second harmonic power spectrum
      of the laser field in a spectral region where the probability of two-photon
      absorption by the molecule is also large. The statistical tools developed are
      general and will help elucidate control mechanisms in future adaptive pulse
      shaping experiments.

PMID- 17530750
TI  - DFT modeling of sandwich complexes involving cationic palladium chains and
      polyenic or polycyclic aromatic hydrocarbons.
AB  - DFT calculations are reported on a series of one-dimensional palladium complexes
      with general formula [Pd(m)(C(2n)H(2n+2))(2)](2+) (m = 2-4, n = 2-8, n > or = m),
      in order to model and analyze the bonding in the series of organometallic
      sandwich compounds recently reported by the group of T. Murahashi and H.
      Kurosawa. The bonding interactions are elucidated, and the frontier orbitals
      involved are described as a function of the haptotropic conformation of the metal
      atoms, either di-hapto or tri-hapto. In both cases, the driving force to the
      complex organization is a strong donation interaction from the pi system of the
      hydrocarbons to an orbital with appropriate phase and composition, delocalized
      over the metal chain, and depopulated by the double oxidation process. No net
      bonding interaction can be characterized along the metal string, and the metal
      metal distances are mainly governed by the hapticities of adjacent atoms. The
      energy associated with the formation of a complex is calculated with respect to
      its fragments, assumed either isolated or solvated. The results emphasize the
      stabilizing role of a large delocalization of the positive charge transferred to
      the hydrocarbons. This delocalization extends to the hydrocarbon regions not
      directly in contact with palladium and highlights the importance of these
      "inactive" regions in complexes made from diphenyl polyenes or polycyclic
      aromatic hydrocarbons. Finally, the bonding pattern deduced from calculations has
      been utilized to consider the feasibility of novel sandwich architectures, whose
      computed energy balance eventually proves similar to that of already existing
      compounds.

PMID- 17530751
TI  - Redox processes in a uranium bis(1,1'-diamidoferrocene) complex.
AB  - Oxidation of a uranium(IV) bis(1,1'-diamidoferrocene) gives a compound which is
      best described as a mixed-valence bisferrocene complex in which uranium mediates
      the electronic communication.

PMID- 17530752
TI  - Plasma-assisted synthesis and properties of Na(3)N.
AB  - Dark-blue sodium nitride, Na(3)N, was prepared by the reaction of metallic sodium
      or liquid Na-K alloy with plasma-activated nitrogen at low pressure. The compound
      crystallizes in the cubic anti-ReO(3)-type structure (space group Pm3m with a =
      4.73301(6) Angstrom and Z = 1) according to powder and single-crystal X-ray
      diffraction data. Na(3)N decomposes above 104 degrees C into the elements, with
      DeltaH(f) estimated at +64(2) kJ/mol.

PMID- 17530753
TI  - Chiral-at-metal ruthenium complex as a metalloligand for asymmetric catalysis.
AB  - The mononuclear [Ru(bpy)(2)(bpym)][PF(6)](2) complex (bpy = 2,2'-bipyridine; bpym
      = 2,2'-bipyrimidine) has been prepared in its enantiopure Lambda form. Because of
      the chelating property of the bipyrimidine moiety, it is possible to use this
      chiral-at-metal complex as a chiral inorganic ligand for a second metal cation
      acting as a catalytic center. Here we report the synthesis and the structural
      characterization of a novel dinuclear Lambda-[(bpy)(2)Ru(bpym)RuCl(p-cymene)](3+)
      compound (1). The asymmetric-inducing properties of the enantiopure chiral-at
      metal metalloligand have been probed during asymmetric transfer hydrogenation to
      ketones catalyzed by 1. This provides one of the very few illustrations of the
      potential of this original class of chiral inorganic ligands.

PMID- 17530754
TI  - Influence of environment on the electronic structure of Cob(III)alamins: time
      resolved absorption studies of the S(1) state spectrum and dynamics.
AB  - Transient absorption spectroscopy has been used to elucidate the nature of the S1
      intermediate state populated following excitation of cob(III)alamin (Cbl(III))
      compounds. This state is sensitive both to axial ligation and to solvent
      polarity. The excited-state lifetime as a function of temperature and solvent
      environment is used to separate the dynamic and electrostatic influence of the
      solvent. Two distinct types of excited states are identified, both assigned to
      pi3d configurations. The spectra of both types of excited states are
      characterized by a red absorption band (ca. 600 nm) assigned to Co 3d --> 3d or
      Co 3d --> corrin pi* transitions and by visible absorption bands similar to the
      corrin pi-->pi* transitions observed for ground state Cbl(III) compounds. The
      excited state observed following excitation of nonalkyl Cbl(III) compounds has an
      excited-state spectrum characteristic of Cbl(III) molecules with a weakened bond
      to the axial ligand (Type I). A similar excited-state spectrum is observed for
      adenosylcobalamin (AdoCbl) in water and ethylene glycol. The excited-state
      spectrum of methyl, ethyl, and n-propylcobalamin is characteristic of a Cbl(III)
      species with a sigma-donating alkyl anion ligand (Type II). This Type II excited
      state spectrum is also observed for AdoCbl bound to glutamate mutase. The results
      are discussed in the context of theoretical calculations of Cbl(III) species
      reported in the literature and highlight the need for additional calculations
      exploring the influence of the alkyl ligand on the electronic structure of
      cobalamins.

PMID- 17530755
TI  - Polyethylene imine derivatives ('synzymes') accelerate phosphate transfer in the
      absence of metal.
AB  - The efficient integration of binding, catalysis, and multiple turnovers remains a
      challenge in building enzyme models. We report that systematic derivatization of
      polyethylene imine (PEI) with alkyl (C(2)-C(12)), benzyl, and guanidinium groups
      gives rise to catalysts ('synzymes') with rate accelerations (k(cat)/k(uncat)) of
      up to 10(4) for the intramolecular transesterification of 2-hydroxypropyl-p
      nitrophenyl phosphate, HPNP, in the absence of metal. The synzymes exhibit
      saturation kinetics (K(M) approximately 250 microM, k(cat) approximately 0.5 min(
      1)) and up to 2340 turnovers per polymer molecule. Catalysis can be specifically
      and competitively inhibited by anionic and hydrophobic small molecules. The
      efficacy of catalysis is determined by the PEI derivatization pattern. The
      derivatization reagents exert a synergistic effect, i.e., their combinations
      increase catalysis by more than the sum of each single modification. The pH-rate
      profile for k(cat)/K(M) is bell shaped with a maximum at pH 7.85 and can be
      explained as a combination of two effects that both have to be operative for
      optimal activity: K(M) increases at high pH due to deprotonation of PEI amines
      that bind the anionic substrate and kcat decreases as the availability of
      hydroxide decreases at low pH. Thus, catalysis is based on substrate binding by
      positively charged amine groups and the presence of hydroxide ion in active sites
      in an environment that is tuned for efficient catalysis. Inhibition studies
      suggest that the basis of catalysis and multiple turnovers is differential
      molecular recognition of the doubly negatively charged transition state (over
      singly charged ground state and product): this contributes a factor of at least 5
      10-fold to catalysis and product release.

PMID- 17530756
TI  - Growth dynamics of CdTe nanoparticles in liquid and crystalline phases.
AB  - Normally the size dependence of the chemical potential is used to explain the
      growth dynamics of semiconductor nanoparticles. Instead we show that very small
      CdTe nanoparticles continue to grow at high dilution, the growth rate is
      virtually independent of monomer concentration, nucleation continues after the
      growth of larger particles has saturated, and the growth rate has a much greater
      nonlinear dependence on particle size than predicted by theory. We suggest that
      nanoparticle growth is fast in the liquid phase and then saturates as the
      particles change phase from liquid to crystal at a threshold size which depends
      on the growth temperature and not the monomer concentration. The
      photoluminescence quantum efficiency becomes high when tellurium is depleted in
      the reaction solution giving a cadmium enriched surface.

PMID- 17530757
TI  - Direct immobilization of Fab' in nanocapillaries for manipulating mass-limited
      samples.
AB  - Interfacing nanoscale elements into a microfluidic device enables a new range of
      fluidic manipulations. Nanocapillary array membranes (NCAMs), consisting of thin
      (5 microm < d < 20 microm) membranes containing arrays of nanometer diameter (10
      nm < a < 500 nm) pores, are a convenient method of interfacing vertically
      separated microchannels in microfluidic devices that allow the external control
      of analyte transport between microfluidic channels. To add functionality to these
      nanopores beyond simple fluid transport, here we incorporate an antibody-based
      molecular recognition element onto the pore surface that allows selective
      capture, purification, and release of specific analytes from a mixture. The pores
      are fabricated by electroless plating of gold into the nanopores of an NCAM (Au
      NCAM). An antibody is then immobilized on the Au-NCAM via gold-thiol chemistry as
      a thiolated fragment of antigen-binding (Fab') prepared by direct digestion of
      the antibody followed by reduction of the disulfide linkage on the hinge region.
      The successful immobilization and biological activity of the resultant Fab'
      through this protocol is verified on planar gold by fluorescence microscopy,
      scanning electron microscopy, and atomic force microscopy. Selective capture and
      release of human insulin is verified using matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry. The relative mass
      spectral peak intensities for insulin versus nonantigenic peptides increase more
      than 20-fold after passing through the Fab'-Au-NCAM relative to the control Au
      NCAM. The affinity-tagged Au-NCAM can be incorporated into microfluidic devices
      to allow the concentration, capture, and characterization of analytes in complex
      mixtures with high specificity.

PMID- 17530758
TI  - Activation of metal hydride complexes by tri-tert-butylphosphine-platinum and 
      palladium groups.
AB  - The compounds HM(CO)4SnPh3, M = Os (10), Ru (11) are activated in the presence of
      Pt(PBut3)2 and Pd(PBu(t)3)2 toward the insertion of PhC2H into the M-H bond. The
      compounds PtOs(CO)4(SnPh3)(PBu(t)3)[mu-HCC(H)Ph], 12, and
      PtOs(CO)4(SnPh3)(PBu(t)3)[mu-H2CCPh], 13, were obtained from the reaction of 10
      with PhC2H in the presence of Pt(PBu(t)3)2. Compounds 12 and 13 are isomers
      containing alkenyl ligands formed by the insertion of the PhC2H molecule into the
      Os-H bond at both the substituted and unsubstituted carbon atoms of the alkyne.
      Both compounds contain a Pt(PBu(t)3) group that is bonded to the osmium atom and
      a bridging alkenyl ligand that is pi-bonded to the osmium atom. The reaction of
      11 with PhC2H in the presence of Pt(PBu(t)3)2 yielded the products
      PtRu(CO)4(SnPh3)(PBu(t)3)[mu-HC2(H)Ph], 14, and PtRu(CO)4(SnPh3)(PBut3)[mu
      H2C2Ph], 15, which are also isomers similar to 12 and 13. The reaction of 11 with
      PhC2H in the presence of Pd(PBu(t)3)2 yielded the product
      PdRu(CO)4(SnPh3)(PBu(t)3)[mu-H2C2Ph], 16. Compound 16 contains a Pd(PBu(t)3)
      group bonded to the ruthenium atom and a bridging H2C2Ph ligand that is pi-bonded
      to the palladium atom. Compound 10 reacted with Pt(PBu(t)3)2 in the absence of
      PhC2H to yield the compound PtOs(CO)4(SnPh3)(PBu(t)3)(mu-H), 17. Compound 17 is a
      Pt(PBu(t)3) adduct of 10. It contains a Pt-Os bond with a bridging hydrido
      ligand. Compound 17 reacted with PhC2H to yield 12. Compound 12 reacted with
      PhC2H to yield the compound PtOs(CO)3(SnPh3)(PBu(t)3)[mu-HCC(Ph)C(H)C(H)Ph], 18.
      Compound 18 contains a bridging 2,4-diphenylbutadienyl ligand, HCC(Ph)C(H)C(H)Ph,
      that is pi-bonded to the osmium atom and sigma-bonded to the platinum atom.
      Fenkse-Hall molecular orbitals of 17 were calculated. The LUMO of 17 exhibits an
      empty orbital on the platinum atom that appears to be the most likely site for
      PhC2H addition prior to its insertion into the Os-H bond.

PMID- 17530759
TI  - Emergence of solution-phase homochirality via crystal engineering of amino acids.
AB  - The evolution of homochirality from a prebiotic environment has long intrigued
      scientists. Here we report how highly enantioenriched solutions may be produced
      by manipulation of amino acid phase behavior, a concept that has far-reaching
      implications for prebiotic chemistry. We demonstrate that the eutectic
      composition of aqueous mixtures of L and D amino acids may be tuned by the
      addition of achiral dicarboxylic acids that cocrystallize with chiral amino
      acids. We find that, in several cases, these systems yield new eutectic
      compositions of 98% ee or higher. This work suggests a forerunner of modern
      crystal engineering that provides a general and facile mechanism for the
      evolution of homochirality as well as a conceptual advance for the separation of
      enantiomers of molecules forming racemic compounds.

PMID- 17530760
TI  - Regio- and stereoselective cross-coupling of substituted olefins and imines. A
      convergent stereoselective synthesis of saturated 1,5-amino-alcohols and
      substituted piperidines.

PMID- 17530761
TI  - Iridium-catalyzed [3 + 2] annulation of 1,3-dienes with ortho-carbonylated
      phenylboronic acids. A catalytic process involving regioselective 1,2-addition.

PMID- 17530762
TI  - Enhancing electron accepting ability of triarylboron via pi-conjugation with 2,2'
      bipy and metal chelation: 5,5'-bis(BMes(2))-2,2'-bipy and its metal complexes.

PMID- 17530763
TI  - Highly sensitive and selective chemosensor for Hg2+ based on the rhodamine
      fluorophore.
AB  - A novel tren-based tripodal chemosensor 1 bearing a rhodamine and two tosyl
      groups was synthesized and its sensing behavior toward metal ions was
      investigated by UV/vis and fluorescence spectroscopies. Addition of a Hg2+ ion to
      a CH3CN solution of 1 gave a visual color change as well as significantly
      enhanced fluorescence, while other ions including Pb2+, Zn2+, Cu2+, Ca2+, Ba2+,
      Cd2+, Co2+, Mg2+, Ag+, Cs+, Li+, and Na+ induced no or much smaller
      color/spectral changes, which constituted a Hg2+-selective fluorescent
      chemosensor (OFF-ON).

PMID- 17530764
TI  - Highly stereoselective 6pi electrocyclization of bridged bicyclic 1,3,5-trienes.
AB  - Conjugated 1,3,5-hexatrienes encased in bridged bicyclic skeletons are prepared
      by cross-coupling followed by half-reduction of the resulting dienynes. The
      trienes undergo 6pi electrocyclization at an ambient or elevated temperature to
      furnish complex, polycyclic cyclohexadienes. In all cases, complete selectivity
      in favor of cyclization from the exo face of the bridged bicyclic system was
      seen, in contrast to the corresponding 4pi Nazarov cyclizations.

PMID- 17530765
TI  - Novel method of aromatic coupling between N-aryl methanesulfonamide and thiophene
      derivatives.
AB  - Oxidation of N-aromatic methanesulfonamides with iodobenzene diacetate in the
      presence of substituted thiophene promotes interesting coupling reactions in
      moderate to good yields.

PMID- 17530766
TI  - Rapid determination of free fatty acids in poultry feed lipid extracts by SB-ATR
      FTIR spectroscopy.
AB  - A simple, rapid, and reproducible method has been developed for the quantitative
      determination of free fatty acid (FFA) content in lipids extracted from poultry
      feeds by Fourier transform infrared (FTIR) spectroscopy with the use of a single
      bounce attenuated total reflectance (SB-ATR) accessory. An FTIR calibration curve
      was prepared by gravimetrically adding oleic acid (15-37%) to pure refined,
      bleached, and deodorized (RBD) canola oil and measuring the area of the COOH
      absorption band at 1710 cm-1. The oil from each of 12 poultry feed formulations
      was extracted using conventional Soxhlet extraction, and after evaporation of the
      solvent, the FFA content was determined by the conventional AOCS titrimetric
      procedure and by the SB-ATR/FTIR method. The SB-ATR/FTIR FFA predictions were
      related to those determined by the AOCS titrimetric method by linear regression,
      producing an R value of 0.999 and a SD of +/-0.28% FFA. Time-course spectra
      collected as lipids extracted into hexane indicated that a 15 min extraction was
      adequate to obtain a representative sample for FFA determination, with further
      extraction resulting in little, if any, change in the proportion of FFA in the
      lipid extract. Only a small volume of the hexane extract ( approximately 20 mL)
      yielded sufficient material for the SB-ATR/FTIR analysis. Thus, by shortening the
      extraction time and taking a small sample so as to reduce solvent removal time,
      the SB-ATR/FTIR procedure provides a very simple and rapid means of determining
      the FFA content of poultry feed lipids.

PMID- 17530767
TI  - A rapid multiplexed chemiluminescent immunoassay for the detection of Escherichia
      coli O157:H7, Yersinia enterocolitica, Salmonella typhimurium, and Listeria
      monocytogenes pathogen bacteria.
AB  - A simple and rapid multiplexed sandwich chemiluminescent enzyme immunoassay has
      been developed for the simultaneous detection of Escherichia coli O157:H7,
      Yersinia enterocolitica, Salmonella typhimurium, and Listeria monocytogenes. To
      achieve the multiplexed detection of the four pathogens, a new polystyrene 96
      well microtiter plate format has been designed, in which each main well contains
      four subwells in the bottom. The monoclonal antibodies specific for each bacteria
      were separately immobilized in each subwell. When the samples were added to the
      main wells, the bacteria able to specifically bind to the corresponding
      monoclonal antibody were captured in one of the four subwells. Subsequently, a
      mixture of peroxidase-labeled polyclonal antibodies against the four bacteria was
      added and the peroxidase activity of the bound polyclonal labeled antibodies in
      each well was measured by an enhanced luminol-based chemiluminescent cocktail
      using a low-light charge-coupled imaging device. The assay was simple and fast,
      and the limit of quantification was in the order of 104-105 CFU/mL for all
      bacterial species. The accuracy of the method, evaluated by comparison of the
      results with a conventional culturing methodology, was satisfactory, with
      recovery values ranging from 90 to 120%. This method can be used as a screening
      test to evaluate the presence of these pathogen bacteria in different foodstuffs.

PMID- 17530768
TI  - Contribution of malolactic fermentation by Oenococcus oeni and Lactobacillus
      plantarum to the changes in the nonanthocyanin polyphenolic composition of red
      wine.
AB  - The changes in the nonanthocyanin phenolic composition during red wine malolactic
      fermentation carried out spontaneously and by four different starter cultures of
      the species Oenococcus oeni and Lactobacillus plantarum were examined to
      determine whether differences in nonanthocyanin polyphenolic compounds could be
      attributed to the lactic acid bacteria (LAB) strain that performs this important
      step of the wine-making process. The polyphenolic compounds were analyzed by high
      performance liquid chromatography with photodiode array detection and HPLC with
      electrospray ionization-mass spectrometry detection. The malolactic cultures
      selected for this study were indigenous wine LAB strains from the A.O.C. Rioja
      (Spain). Results showed different malolactic behaviors in relation to wine
      phenolic compositions for O. oeni and L. plantarum, and also, a diversity was
      found within each group. The hydroxycinnamic acids and their derivatives, the
      flavonols and their glycosides, the flavanol monomers and oligomers, and trans
      resveratrol and its glucoside were the main compounds modified by the different
      LAB. The wild LAB population exerted a greater impact in the wine content of some
      of these phenolic compounds than the inoculated selected monocultures of this
      study.

PMID- 17530769
TI  - Simple purification (desalting) procedure to facilitate structural analysis of an
      alkali-solubilized/neutralized starch solution by intermediate-pressure size
      exclusion chromatography.
AB  - A technique was established to remove impurities (e.g., salts) from starch
      dissolved in strong alkali and neutralized with acid to accommodate starch
      structural analysis via intermediate-pressure size-exclusion chromatography
      (IPSEC). Starch (corn and wheat) subjected to an alkaline-microwave dissolution
      scheme (35 s microwave heating in a mixture of 6 M urea and 1 M KOH) was either
      treated with ion-exchange resin or passed through a desalting column to remove
      salt/urea contaminants. Control (untreated) starch solution analyzed by IPSEC
      displayed a significant interfering peak (attributable to salt/urea), which
      coeluted with the starch amylose peak. The interfering peak was most efficiently
      eliminated by first passing the starch solution through a desalting column, which
      process effectively removed impurities (e.g., salts/urea) without appearing to
      adversely impact the starch structural analysis. This simple technique coupled
      with the rapid alkaline-microwave starch dissolution procedure greatly expedites
      structural investigation of starch by facilitating analysis by IPSEC.

PMID- 17530770
TI  - Alternaria alternata Crofton-weed toxin: a natural inhibitor of photosystem II in
      Chlamydomonas reinhardtii thylakoids.
AB  - The action site of Alternaria alternata Crofton-weed toxin (AAC-toxin), isolated
      first from Alternaria alternata (Fr.) Keissler, was investigated in Chlamydomonas
      reinhardtii thylakoids. The results revealed that AAC-toxin inhibited
      photophosphorylation in a concentration-dependent pattern. Similarly, toxin
      inhibited uncoupled, basal electron flow and photosystem II (PSII) electron
      transport as well. However, toxin did not affect photosystem I (PSI) activity or
      the partial reaction of electron transport from H2O to silicomolybdic acid
      (SiMo). Therefore, the action site of toxin was located at QB level. In addition,
      the toxin may behave as an energy-transfer inhibitor at high concentrations by
      inhibiting phosphorylating electron transport and Mg2+ATPase activity.
      Chlorophyll a fluorescence induction and JIP test corroborated the inhibition at
      QB level. Through observations of the different sensitivity of toxin on D1
      mutants of C. reinhardtii, evidence further confirmed that AAC-toxin inhibited
      electron transport by displacing the QB on the D1 protein, and the mode of action
      was similar to phenol-type PSII inhibitors.

PMID- 17530771
TI  - Propolin H from Taiwanese propolis induces G1 arrest in human lung carcinoma
      cells.
AB  - Propolis, a natural product collected by honeybee, has been reported to exert a
      wide spectrum of biological functions. In this study, we have isolated a novel
      component, namely, propolin H, and investigated its effects in human carcinoma
      cells. Propolin H inhibited the proliferation of human lung carcinoma cell lines
      in MTT assay, and a significant G1 arrest was observed to occur in a dose
      dependent manner at 24 h of exposure in H460 cells. After treatment with propolin
      H in H460 cells, the content of the CDK inhibitor p21Waf1/Cip1 protein increased
      in correlation with the elevation in p53 levels. Western blot analysis of G1
      regulatory proteins further revealed a decrease in cyclin-dependent kinase 2
      (CDK2) and CDK4 and an increase in cyclin E. The CDKs kinase activities assay
      showed that propolin H has inhibited CDK2 and CDK4 kinase activities.
      Accordingly, coimmunoprecipitations revealed an increased association of both
      CDK2 and CDK4 immunoreactive protein with the p21Waf1/Cip1 protein complex under
      propolin H-treated conditions. Additionally, we found that propolin H enhanced
      the expression of p21Waf1/Cip1 in p53-mutant and p53-null lung carcinoma cell
      lines, following the induction of G1 arrest. Together, these findings suggest
      that the induction of p21Waf1/Cip1 expression occurred through p53-dependent and 
      independent pathways in propolin H-treated cells. Propolin H exerts its
      significantly growth inhibitory effects and may have therapeutic applications.

PMID- 17530772
TI  - Simultaneous analysis of catechins, gallic acid, strictinin, and purine alkaloids
      in green tea by using catechol as an internal standard.
AB  - We developed a high-performance liquid chromatography-based method for
      simultaneous analysis of nine catechins, gallic acid, strictinin, caffeine, and
      theobromine in green tea by using catechol as an internal standard. Although the
      high cost and instability of the catechin reference standards limit the
      application of this method, the addition of ascorbic acid to the standard stock
      solution preserved the stability of the reference standards in the solution for 1
      year when stored at -30 degrees C. Furthermore, we found that the slopes of the
      calibration curves plotted were stable for a run time of 2000 h. Our method
      proved to be appropriate for quantification and yielded good correlation
      coefficients, detection levels, repeatability, reproducibility, and recovery
      rates. Quantitative data revealed that the contribution of only 200 mL of brewed
      tea to the total dietary catechins was approximately 220-420 mg, while that of
      500 mL of bottled tea was approximately 170-900 mg.

PMID- 17530773
TI  - Changes in free amino acids and sugars in potatoes due to sulfate fertilization
      and the effect on acrylamide formation.
AB  - To examine how sulfur deprivation may affect acrylamide formation in cooked
      potatoes, three varieties of potato were grown under conditions of either severe
      sulfur deprivation or an adequate supply of sulfur. In all three varieties sulfur
      deprivation led to a decrease in acrylamide formation, even though the levels of
      sugars, which are acrylamide precursors, were higher in tubers of the sulfur
      deprived plants. In one variety the concentration of free asparagine, the other
      precursor for acrylamide, was also higher. There was a very close correlation
      between the concentration of asparagine in the tubers expressed as a proportion
      of the total free amino acid pool and the formation of acrylamide upon cooking,
      whereas sugars were poorly correlated with acrylamide. In potatoes, where
      concentrations of sugars are usually limiting, competition between asparagine and
      other amino acids participating in the Maillard reaction may be a key determinant
      of the amount of acrylamide that is formed during processing.

PMID- 17530774
TI  - Identification and quantification of carotenoids, by HPLC-PDA-MS/MS, from
      Amazonian fruits.
AB  - The major and minor carotenoids from six fruits, buriti (Mauritia vinifera),
      mamey (Mammea americana), marimari (Geoffrola striata), peach palm (Bactrys
      gasipaes), physalis (Physalis angulata), and tucuma (Astrocaryum aculeatum), all
      native to the Amazonia region, were determined by high-performance liquid
      chromatography-photodiode array detector-mass spectrometry detector (HPLC-PDA
      MS/MS), fulfilling the recommended criteria for identification. A total of 60
      different carotenoids were separated on a C30 column, all-trans-beta-carotene
      being the major carotenoid found in all fruits. The presence of apo-10'-beta
      carotenol, found in mamey, was not previously reported in foods. In addition,
      this is the first time that the identification of beta-zeacarotene in natural
      sources is supported by MS data. The total carotenoid content ranged from 38
      microg/g in marimari to 514 microg/g in buriti. All fruits analyzed can be
      considered good sources of provitamin A, especially buriti, with 7280 RE/100 g.

PMID- 17530775
TI  - Estimation of drug precipitation upon dilution of pH-controlled formulations.
AB  - An equation is developed for estimating the precipitation that may occur upon
      diluting or injecting a (pH-)solubilized drug formulation. Since it is based on
      equilibrium, it is the worst case scenario for precipitation. This equation can
      be programmed in any commercially available spread sheet program such as Excel.
      According to the proposed equation, the type and the strength of the buffer
      species are the most significant factors that affect the pH and solubility of a
      drug in its microenvironment during dilution. To demonstrate the utility and
      robustness of the proposed equation, experimental measurements were performed
      using phenytoin as the model drug. The result suggests that the proposed equation
      can be used to indicate the possibility and the degree of precipitation that
      would occur upon injection. This provides a useful tool for the design of a
      successful pH-controlled solution formulation.

PMID- 17530776
TI  - The Rule of Five revisited: applying log D in place of log P in drug-likeness
      filters.
AB  - The much publicized "Rule of 5" has been widely adopted among the pharmaceutical
      industry. It is used as a first step filter to perform virtual screening of
      compound libraries, in an effort to quickly eliminate lead candidates that have
      poor physicochemical properties for oral bioavailabilty. One of the key
      parameters used therein is log P, which is a useful descriptor, but one that
      fails to take into account variation in the lipophilicity of a drug with respect
      to the ionic states present at key biological pH values. Given that the majority
      of commercial pharmaceuticals contain an ionizable moiety, we propose that log D
      is a better descriptor for lipophilicity in the context of the Rule of 5. It
      gives more physiologically relevant results, thereby reducing the number of
      potential false-negatives incorrectly eliminated in screening. Using a series of
      commercial compound libraries, this study showed that the adapted Rule of 5 using
      log D instead of log P provides notable improvement in pass rate for compounds
      that have the desired lipophilicity at a relevant physiological pH.

PMID- 17530777
TI  - Potentiometric immunoassay with quantum dot labels.
AB  - Potentiometric sensors based on polymer membrane electrodes, if properly
      optimized, are useful for measurements at trace levels. The expected independence
      of the electrochemical signal of the sample size makes them extremely attractive
      for measurements in small volumes. Here, we report on electrodes for the
      potentiometric detection of cadmium ions that reach a detection limit of 6 nM and
      utilize a Na(+)-selective electrode as pseudoreference in order to facilitate
      measurements in 150-microL samples. A potentiometric immunoassay of mouse IgG is
      performed via CdSe quantum dot labels on a secondary antibody according to a
      sandwich immunoassay protocol in a microtiter plate format. The CdSe quantum dots
      are found to be easily dissolved/oxidized in a matter of minutes with hydrogen
      peroxide, allowing us to maintain the pH at a near-neutral value. The
      potentiometric protein immunoassay exhibits a log-linear response ranging from
      0.15 to 4.0 pmol of IgG, with a detection limit of <10 fmol in 150-microL sample
      wells.

PMID- 17530778
TI  - Selective binding of carotenoids with a shorter conjugated chain to the LH2
      antenna complex and those with a longer conjugated chain to the reaction center
      from Rubrivivax gelatinosus.
AB  - Rubrivivax gelatinosus having both the spheroidene and spirilloxanthin
      biosynthetic pathways produces carotenoids (Cars) with a variety of conjugated
      chains, which consist of different numbers of conjugated double bonds (n),
      including the C=C (m) and C=O (o) bonds. When grown under anaerobic conditions,
      the wild type produces Cars for which n = m = 9-13, whereas under semiaerobic
      conditions, it additionally produces Cars for which n = m + o = 10 + 1, 13 + 1,
      and 13 + 2. On the other hand, a mutant, in which the latter pathway is
      genetically blocked, produces only Cars for which n = 9 and 10 under anaerobic
      conditions and n = 9, 10, and 10 + 1 under semianaerobic conditions. Those Cars
      that were extracted from the LH2 complex (LH2) and the reaction center (RC),
      isolated from the wild-type and the mutant Rvi. gelatinosus, were analyzed by
      HPLC, and their structures were determined by mass spectrometry and 1H NMR
      spectroscopy. The selective binding of Cars to those pigment-protein complexes
      has been characterized as follows. (1) Cars with a shorter conjugated chain are
      selectively bound to LH2 whereas Cars with a longer conjugated chain to the RC.
      (2) Shorter chain Cars with a hydroxyl group are bound to LH2 almost exclusively.
      This rule holds either in the absence or in the presence of the keto group. The
      natural selection of shorter chain Cars by LH2 and longer chain Cars by the RC is
      discussed, on the basis of the results now available, in relation to the light
      harvesting and photoprotective functions of Cars.

PMID- 17530779
TI  - Interaction of the PHD-finger homeodomain protein HAT3.1 from Arabidopsis
      thaliana with DNA. Specific DNA binding by a homeodomain with histidine at
      position 51.
AB  - HAT3.1 is a member of the PHD-finger homeodomain protein family. The HAT3.1
      homeodomain is highly divergent in sequence even at positions that are almost
      invariable among homeodomains. In this work, we have applied the random
      oligonucleotide selection technique to investigate if the HAT3.1 homeodomain is
      able to recognize specific DNA sequences. Analysis of the selected molecules
      followed by hydroxyl radical footprinting experiments and yeast one-hybrid assays
      indicated that HAT3.1 shows a preference for the sequence T(A/G)(A/C)ACCA,
      different from those bound by other homeodomains. Binding was dependent on
      homeodomain residues located at positions 47, 50, 51, and 54, the same positions
      that usually participate in DNA binding in most homeodomains. The study of the
      interaction of mutants at these positions with DNA carrying nucleotide changes at
      specific sites suggested that H51 and K50 most likely interact with nucleotides 2
      to 4 and 5 to 6, respectively, while W54 would establish contacts with position
      4. The presence of H51 and W54 represents an innovation among homeodomain
      structures. The fact that the HAT3.1 homeodomain is able to interact with
      specific DNA sequences is evidence of the inherent plasticity of the homeodomain
      as a DNA binding unit.

PMID- 17530780
TI  - The impact of the E46K mutation on the properties of alpha-synuclein in its
      monomeric and oligomeric states.
AB  - The third and most recently identified Parkinson's disease-linked variant of the
      neuronal protein alpha-synuclein to be identified (E46K) results in widespread
      brain pathology and early onset Parkinson symptoms (Zarranz et al. (2004) Ann.
      Neurol. 55, 164-173). Herein, we present biochemical and biophysical
      characterization of E46K alpha-synuclein in various states of aggregation.
      Circular dichroism and nuclear magnetic resonance spectroscopy illustrate that
      the E46K mutation results in subtle changes in the conformation of the monomeric
      protein both free in solution and in the presence of SDS micelles. However, it
      does not alter the overall helical propensity of the protein in the presence of
      phospholipids. E46K alpha-synuclein formed insoluble fibrils in vitro more
      rapidly than the wild type protein, and electron microscopy revealed that E46K
      alpha-synuclein fibrils possess a typical amyloid ultrastructure. E46K alpha
      synuclein protofibrils, soluble aggregates that form during the transition from
      the monomeric form to the fibrillar form of alpha-synuclein, were characterized
      by electron microscopy and gel filtration and were found to include annular
      species. The unique ability of a subfraction of E46K and wild type alpha
      synuclein protofibrils containing porelike species to permeabilize lipid vesicles
      was demonstrated in vitro using a real-time chromatographic method. In contrast
      to simplistic expectations, the total amount of protofibrils and the amount of
      permeabilizing activity per mole protein in the protofibril fraction were reduced
      by the E46K mutation. These results suggest that if the porelike activity of
      alpha-synuclein is important for neurotoxicity, there must be factors in the
      neuronal cytoplasm that reverse the trends in the intrinsic properties of E46K
      versus WT alpha-synuclein that are observed in vitro.

PMID- 17530781
TI  - Identification of tubulin as a substrate of Jak2 tyrosine kinase and its role in
      Jak2-dependent signaling.
AB  - Jak2 is a nonreceptor tyrosine kinase that acts in numerous cellular signal
      transduction systems. Here, large amounts of recombinant Jak2 protein were
      expressed in eukaryotic cells, and an unknown 55 kDa protein was copurified with
      it. Mass spectrometry and Western blot analysis identified the 55 kDa protein as
      the alpha- and beta-isoforms of tubulin. Biochemical experiments determined that
      Jak2 and tubulin specifically coassociate with one another, and the region of
      Jak2 that binds tubulin is the pseudokinase domain. Immunofluoresence indicated
      that Jak2 and tubulin (microtubules) colocalize within intact cells. The
      functional consequence of the coassociation between Jak2 and tubulin is that Jak2
      phosphorylates tubulin on tyrosine residues. Specifically, in response to growth
      hormone, tubulin was phosphorylated in a Jak2-dependent manner. Tubulin was also
      found to interact with signal transducers and activators of transcription 1
      (STAT1) and be involved in STAT1 nuclear transport. As such, this work suggests
      that tubulin is a substrate of Jak2 and facilitates Jak2/STAT1-dependent
      signaling.

PMID- 17530782
TI  - CmaE: a transferase shuttling aminoacyl groups between carrier protein domains in
      the coronamic acid biosynthetic pathway.
AB  - During the biosynthesis of the cyclopropyl amino acid coronamic acid from l-allo
      Ile by the phytotoxic Pseudomonas syringae, the aminoacyl group covalently
      attached to the pantetheinyl arm of CmaA is shuttled to the HS-pantetheinyl arm
      of the protein CmaD by the aminoacyltransferase CmaE. CmaE will only recognize
      deacylated CmaA for initial complexation. The aminoacyl group becomes covalently
      attached to the active site Cys of CmaE and can then be transferred out to the
      holo pantetheinylated form of CmaD. Both l-Val/l-[14C]Val exchange studies and
      MALDI-TOF support a reversible shuttling process. Aminoacylated-S-CmaE will
      transfer the l-Val moiety to the HS-pantetheinyl arm of other T domains,
      including CytC2, BarA, and ArfA C2-A2-T2 but not to free HS-pantetheine. CmaD
      could be loaded with other amino acids, for example, l-Leu and l-Thr, by the
      action of heterologous donor T domains containing alternative aminoacyl groups.
      Additionally, CmaE is able to accept l-Phe as a substrate when presented on CmaD
      and is able to load this aminoacyl moiety onto heterologous T domains, expanding
      the potential for CmaE to be used as a tool for generating chemical diversity
      within an NRPS assembly line.

PMID- 17530783
TI  - Differential stability of dimeric and monomeric cytochrome c oxidase exposed to
      elevated hydrostatic pressure.
AB  - Detergent-solubilized dimeric and monomeric cytochrome c oxidase (CcO) have
      significantly different quaternary stability when exposed to 2-3 kbar of
      hydrostatic pressure. Dimeric, dodecyl maltoside-solubilized cytochrome c oxidase
      is very resistant to elevated hydrostatic pressure with almost no perturbation of
      its quaternary structure or functional activity after release of pressure. In
      contrast to the stability of dimeric CcO, 3 kbar of hydrostatic pressure triggers
      multiple structural and functional alterations within monomeric cytochrome c
      oxidase. The perturbations are either irreversible or slowly reversible since
      they persist after the release of high pressure. Therefore, standard biochemical
      analytical procedures could be used to quantify the pressure-induced changes
      after the release of hydrostatic pressure. The electron transport activity of
      monomeric cytochrome c oxidase decreases by as much as 60% after exposure to 3
      kbar of hydrostatic pressure. The irreversible loss of activity occurs in a time-
      and pressure-dependent manner. Coincident with the activity loss is a sequential
      dissociation of four subunits as detected by sedimentation velocity, high
      performance ion-exchange chromatography, and reversed-phase and SDS-PAGE subunit
      analysis. Subunits VIa and VIb are the first to dissociate followed by subunits
      III and VIIa. Removal of subunits VIa and VIb prior to pressurization makes the
      resulting 11-subunit form of CcO even more sensitive to elevated hydrostatic
      pressure than monomeric CcO containing all 13 subunits. However, dimeric CcO, in
      which the association of VIa and VIb is stabilized, is not susceptible to
      pressure-induced inactivation. We conclude that dissociation of subunit III
      and/or VIIa must be responsible for pressure-induced inactivation of CcO since
      VIa and VIb can be removed from monomeric CcO without significant activity loss.
      These results are the first to clearly demonstrate an important structural role
      for the dimeric form of cytochrome c oxidase, i.e., stabilization of its
      quaternary structure.

PMID- 17530784
TI  - DC-81-Indole conjugate agent induces mitochondria mediated apoptosis in human
      melanoma A375 cells.
AB  - DC-81, an antitumor antibiotic produced by the Streptomyces species, belongs to
      pyrrolo[2,1-c] [1,4]benzodiazepine (PBD), which are potent inhibitors of nucleic
      acid synthesis. We previously reported an efficient synthesis of PBD hybrids
      linked with indole carboxylates. This is the first demonstration on the mechanism
      of the anticancer effect of PBD hybrid (IN6CPBD) agent on human melanoma A375
      cells. IN6CPBD-treated cells exhibited higher cytotoxicity than DC-81 and
      displayed several features of apoptosis, including an increase in the sub-G1
      population, a significantly increased annexin V binding, a degradation of caspase
      3, and poly (ADP-ribose) polymerase (PARP) cleavage. Because degradative changes
      associated with apoptosis are often preceded by the disruption of mitochondrial
      function, the assessment of mitochondrial function in IN6CPBD-treated cells is
      worthy of investigation. Our data revealed that treatment of A375 cells with
      IN6CPBD resulted in the loss of mitochondrial membrane potential (DeltaPsimt), a
      decrease in intracellular pH (pHi), a reduction of ATP synthesis, increased
      reactive oxygen species (ROS) generation, and cytochrome c release. Collectively,
      our studies indicate that IN6CPBD induces apoptosis in A375 cells through a
      mitochondrial dysfunction pathway, leading to caspase-3 substrate PARP cleavage
      and subsequent apoptotic cell death.

PMID- 17530785
TI  - Selective adsorption of volatile organic compounds in micropore aluminum
      methylphosphonate-alpha: a combined molecular simulation-experimental approach.
AB  - Results concerning the adsorption capacity of aluminum methylphosphonate
      polymorph alpha (AlMePO-alpha) for pure ethyl chloride and vinyl chloride by
      measured individual adsorption isotherms of these pure compounds are presented
      and discussed here. The experimental data supports the idea of using these
      materials as selective adsorbents for separating these compounds in mixtures. To
      explore this possibility further, we have performed grand canonical Monte Carlo
      simulations using a recently proposed molecular simulation framework for gas
      adsorption on AlMePO, and the results are presented here. The molecular model of
      the material was used in a purely transferable manner from a previous work
      (Herdes, C.; Lin, Z.; Valente, A.; Coutinho, J. A. P.; Vega, L. F. Langmuir 2006,
      22, 3097). Regarding the molecular model of the fluids, an existing model for
      ethyl chloride was improved to capture the experimental dipole value better; an
      equivalent force field for the vinyl chloride molecule was also developed for
      simulation purposes. Simulations of the pure compounds were found to be in
      excellent agreement with the measured experimental data at the three studied
      temperatures. Simulations were also carried out in a purely predictive manner as
      a tool to find the optimal conditions for the selective adsorption of these
      compounds prior experimental measurements are carried out. The influence of the
      temperature and the bulk composition on the adsorption selectivity was also
      investigated. Results support the use of AlMePO-alpha as an appropriate adsorbent
      for the purification process of vinyl chloride, upholding the selective
      adsorption of ethyl chloride.

PMID- 17530786
TI  - Role of dipolar interaction in the mesoscopic domains of phospholipid monolayers:
      dipalmitoylphosphatidylcholine and dipalmitoylphosphatidylethanolamine.
AB  - The role of dipolar interactions in determining the lipid domain shapes at the
      air-water interface with a change in the chemical structure of the head groups of
      lipids is theoretically studied. The phospholipids considered are
      dipalmitoylphosphatidylcholine (D,L-DPPC) and dipalmitoylphosphatidylethanolamine
      (DPPE). Despite closely similar chemical structures, the domains of the two
      lipids are strikingly different. The DPPC domains exhibit elongated arms, while
      the DPPE domains are nearly round-shaped. To compare the dipolar repulsions in
      the domains of the two phospholipids, different energy-minimized conformers of
      DPPC and DPPE are studied using the semiempirical quantum chemical method (PM3).
      It is found that the dipole moment of DPPC is significantly larger than that of
      DPPE. The in-plane and out-of-plane components of the dipole moments are
      calculated using grazing incidence X-ray diffraction data at different surface
      pressure values, as used in the experiment. The result indicates that the
      magnitude of the dipolar interaction is significantly larger in DPPC than that in
      DPPE over the surface pressure range considered. The enhanced dipolar repulsion
      corroborates well with the difference in the domain shapes in the two
      phospholipid monolayers. The larger dipolar repulsion in DPPC leads to
      development of elongated domain arms, while relatively less dipolar repulsion
      allows a closed shape of the condensed-phase DPPE domains.

PMID- 17530787
TI  - Calibration of friction force signals in atomic force microscopy in liquid media.
AB  - The calibration factors for atomic force microscopy (AFM) friction force
      measurements in liquid media are shown to be different by 25-74% compared to
      measurements in air. Even though it is significantly more precise, the improved
      wedge calibration method using a universal calibration specimen suffers, as all
      other widely applied methods, from the drawback that friction force calibration
      factors acquired in air cannot be used for measurements in liquids for the most
      common liquid cell designs. The effect of laser light refraction and the
      dependence of the calibration factors on the refractive index of the imaging
      medium is captured quantitatively in a simple model that allows one to
      conveniently rescale the values of lateral photodiode sensitivity obtained in
      air. Hence a simple, yet precise calibration of lateral forces is now also
      feasible for AFM in liquids.

PMID- 17530788
TI  - Thermal behavior of J-aggregates in mixed Langmuir-Blodgett films composed of
      merocyanine dye and deuterated arachidic acid investigated by UV-visible and
      infrared absorption spectroscopy.
AB  - We have investigated the thermal behavior of J-aggregates in the mixed Langmuir
      Blodgett (LB) films composed of the merocyanine dye (MS18)-deuterated arachidic
      acid (C20-d) binary system in the temperature range from 25 to 250 degrees C by
      means of UV-visible and IR transmission absorption spectroscopy. The temperature
      dependent variations in both UV-visible and IR absorption spectra indicate that
      the MS18 aggregation states are linked with the MS18 intramolecular charge
      transfer and the behavior of the packing, orientation, conformation, and thermal
      mobility of the MS18 hydrocarbon chain. The J-aggregate formed at 25 degrees C in
      the mixed LB films dissociates in the temperature range from 25 to 110 degrees C,
      which is mainly ascribed to the increase in the thermal mobility of MS18
      hydrocarbon chain and the dissociation of the chelation by a cadmium ion to the
      MS18 keto group. A thermally induced blue-shifted band appears at around 515 nm
      from 110 to 160 degrees C. This band is attributed to oligomeric aggregation with
      side-by-side alignment of the MS18 transition dipole moments on the basis of the
      shift to a higher-energy side, broadening, and temporary increment of the MS18
      intramolecular charge transfer of the band. Consequently, the appearance of the
      thermally induced blue-shifted band indicates the possibility that the MS18
      aggregation states can be controlled from the red shift to the blue shift by the
      annealing method adopted in the present study.

PMID- 17530789
TI  - Fabrication of metallized nanoporous films from the self-assembly of a block
      copolymer and homopolymer mixture.
AB  - Inorganic compound HAuCl4, which can form a complex with pyridine, is introduced
      into a poly(styrene-block-2-vinylpyridine) (PS-b-P2VP) block
      copolymer/poly(methyl methacrylate) (PMMA) homopolymer mixture. The orientation
      of the cylindrical microdomains formed by the P2VP block, PMMA, and HAuCl4 normal
      to the substrate surface can be generated via cooperative self-assembly of the
      mixture. Selective removal of the homopolymer can lead to porous nanostructures
      containing metal components in P2VP domains, which have a novel photoluminescence
      property.

PMID- 17530790
TI  - Adsorption to metal oxides of the Pseudomonas aeruginosa siderophore pyoverdine
      and implications for bacterial biofilm formation on metals.
AB  - The initiation of biofilm formation is poorly understood, and in particular, the
      contribution of chemical bond formation between bacterial cells and metal
      surfaces has received little attention. We have previously used in situ infrared
      spectroscopy to show, during the initial stages of Pseudomonas aeruginosa biofilm
      formation, the formation of coordinate covalent bonds between titanium dioxide
      particle films and pyoverdine, a mixed catecholate and hydroxamate siderophore.
      Here we show using infrared spectroscopy that pyoverdine can also form covalent
      bonds with particle films of Fe2O3, CrOOH, and AlOOH. Adsorption to the metal
      oxides through the catechol-like 2,3-diamino-6,7-dihydroxyquinoline part of
      pyoverdine was most evident in the infrared spectrum of the adsorbed pyoverdine
      molecule. Weaker infrared absorption bands that are consistent with the
      hydroxamic acids of pyoverdine binding covalently to TiO2, Fe2O3, and AlOOH
      surfaces were also observed. The adsorption of pyoverdine to TiO2 and Fe2O3
      surfaces showed a pH dependence that is indicative of the dominance of the
      catechol-like ligand of pyoverdine. Infrared absorption bands were also evident
      for pyoverdine associated with the cells of P. aeruginosa on TiO2 and Fe2O3
      surfaces and were notably absent for genetically modified cells unable to
      synthesize or bind pyoverdine at the cell surface. These studies confirm the
      generality of pyoverdine-metal bond formation and suggest a wider involvement of
      siderophores in bacterial biofilm initiation on metals.

PMID- 17530791
TI  - Differential scanning calorimetry and Fourier transform infrared spectroscopic
      studies of phospholipid organization and lipid-peptide interactions in nanoporous
      substrate-supported lipid model membranes.
AB  - High-sensitivity differential scanning calorimetry was utilized to examine
      whether lipids capable of forming an inverted nonlamellar hexagonal II (HII)
      phase can be deposited into nanoporous substrate-supported arrays. Particularly,
      we compare the thermotropic phase properties of nanoconfined unsaturated 1
      palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine lipid bilayers with
      unsupported dispersions to assess nanoconfinement effects, focusing on the
      lamellar fluid (Lalpha) to HII phase transition. Experimental results provide
      direct and clear evidence for the formation of an HII phase upon both heating and
      cooling. However, a small shift in the Lalpha/HII phase transition temperature,
      as well as an increase in the magnitude of the associated temperature hysteresis,
      was observed in the nanoporous substrate-supported system. Additionally,
      nanoconfinement effects on the interaction and location of the antimicrobial
      peptide gramicidin S (GS) with nanoporous substrate-supported cardiolipin
      bilayers were examined by Fourier transform infrared spectroscopy as a function
      of temperature and phospholipid phase state. Upon heating, GS molecules began to
      insert into nanoconfined, substrate-supported cardiolipin bilayers at lower
      temperatures relative to the gel/liquid-crystalline phase transition temperature
      than into unsupported bilayers. The reduction in the polarity and hydrogen
      bonding potential environment of GS in the Lalpha state suggests that GS is
      located at the polar/apolar interfacial region in both supported and unsupported
      cardiolipin bilayers and that the capacity of GS to interact with nanoporous
      substrate-supported cardiolipin bilayers was not significantly hindered by
      nanoconfinement. These studies further demonstrate the usefulness of supported
      lipid bilayers inside nanoporous substrates.

PMID- 17530792
TI  - Robust determinants of thermostability highlighted by a codon frequency index
      capable of discriminating thermophilic from mesophilic genomes.
AB  - Can genome analysis tell us about the lifestyle of an organism? We ask this
      question considering a thorough cross comparison of thermophilic and mesophilic
      genomes, since presently the number of available genomes is enough to ensure
      statistical significance of the results. We analyze, by means of principal
      component analysis (PCA), the codon composition of a database comprising 116
      genomes, selected so as to include one species for each genus and show that a
      cross genomic approach can allow the extraction of common determinants of
      thermostability at the genome level. The results of our analysis indicate that
      all the known features of thermostability can be found in the 64 component
      loadings of the second principal axis of PCA. By this, we develop an index of
      thermostability whose discriminative power between mesophiles and thermophiles
      scores with 98% accuracy at the genome level and with 95% accuracy at the protein
      sequence level. We also prove that these results are not due to phylogenetic
      differences between archaea and bacteria.

PMID- 17530793
TI  - Multiple binding modes for dicationic Hoechst 33258 to DNA.
AB  - The binding of dicationic Hoechst 33258 (ligand) to DNA was characterized by
      means of the fluorescence spectra, fluorescence intensity titration, time
      resolved fluorescence decay, light scattering, circular dichroism, and
      fluorescence thermal denaturation measurements, and two binding modes were
      distinguished by the experimental results. Type 1 binding has the stoichiometry
      of one ligand to more than 12 base pairs, and it is defined as quasi-minor groove
      binding which has the typical prolonged fluorescence lifetime of about 4.4 ns. In
      type 1 binding, planar conformation of the ligand is favorable. Type 2 binding
      with phosphate to ligand ratio (P/L) < 2.5 has the stoichiometry of one ligand to
      two phosphates. It is defined as a highly dense and orderly stacked binding with
      DNA backbone as the template. Electrostatic interactions between doubly
      protonated ligands and negatively charged DNA backbone play a predominant role in
      the type 2 binding mode. The characteristics of this type of binding result in a
      twisted conformation of the ligand that has a fluorescence lifetime of less than
      1 ns. The results also indicate that the binding is in a cooperative manner
      primarily by stacking of the aromatic rings of the neighboring ligands. Type 1
      binding is only observed for double-stranded DNA (dsDNA) with affinity constant
      of 1.83 x 10(7) M-1. In the type 2 binding mode, the binding affinity constants
      are 4.9 x 10(6) and 4.3 x 10(6) M-1 for dsDNA and single-stranded DNA (ssDNA),
      respectively. The type 2 binding is base pair independent while the type 1
      binding is base pair related. The experiments described in this paper revealed
      that the dication bindings are different from the monocation bindings reported by
      previous study. The dication binding leads to stronger aggregation at low ligand
      concentration and results in orderly arrangements of the ligands along DNA
      chains. Furthermore the dication binding is demonstrated to be beneficial for
      enhancing the DNA's stability.

PMID- 17530794
TI  - Water-barrier properties of mixed bis[trimethoxysilylpropyl]amine and
      vinyltriacetoxysilane films.
AB  - X-ray and neutron reflectivity were employed to elucidate the morphologies of
      bis[trimethoxysilylpropyl]amine silane (A) and vinyltriacetoxysilane (V) mixed
      films on Si wafers at different A/V ratios, and the response of these films to
      saturated water vapor. Due to its insensitivity to chemical composition, X-ray
      reflectivity was used to assess the film density, whereas neutron reflectivity
      was used to probe water absorption and chemical change on exposure to water. NMR
      was employed to determine the reaction mechanism in neat AV mixtures and
      stoichiometry of the initial reaction. X-ray reflectivity reveals about 30% void
      volume in the films with the least void volume detected near stoichiometry.
      Grazing incidence small-angle scattering (GISAXS) shows that the void volume is
      at the molecular level, with no distinct pores. Neutron reflectivity on D2O
      conditioned films shows that silane film is not an effective water barrier with
      about 30 vol % water being absorbed with only a slight thickness increase. Most
      water is physically absorbed in the void space with the least amount being
      absorbed near the stoichiometric A/V ratio. The scattering length density of the
      films almost returns to the virgin state after re-dry following D2O vapor
      exposure. The film thickness, however, remains at the water-vapor-conditioned
      state. The slight increase in scattering length density and irreversible
      thickness change after re-dry indicate some reaction with water during D2O
      conditioning. A D-rich layer is also observed at the air side surface in D2O
      conditioned films regardless of A/V ratio.

PMID- 17530795
TI  - Calculation of free energies and chemical potentials for gas hydrates using Monte
      Carlo simulations.
AB  - We describe a method for calculating free energies and chemical potentials for
      molecular models of gas hydrate systems using Monte Carlo simulations. The method
      has two components: (i) thermodynamic integration to obtain the water and guest
      molecule chemical potentials as functions of the hydrate occupancy; (ii)
      calculation of the free energy of the zero-occupancy hydrate system using
      thermodynamic integration from an Einstein crystal reference state. The approach
      is applicable to any classical molecular model of a hydrate. We illustrate the
      methodology with an application to the structure-I methane hydrate using two
      molecular models. Results from the method are also used to assess approximations
      in the van der Waals-Platteeuw theory and some of its extensions. It is shown
      that the success of the van der Waals-Platteeuw theory is in part due to a
      cancellation of the error arising from the assumption of a fixed configuration of
      water molecules in the hydrate framework with that arising from the neglect of
      methane-methane interactions.

PMID- 17530796
TI  - Measuring electronic coupling in the reaction center of purple photosynthetic
      bacteria by two-color, three-pulse photon echo peak shift spectroscopy.
AB  - One- and two-color, three-pulse photon echo peak shift spectroscopy (1C and
      2C3PEPS) was used to estimate the electronic coupling between the accessory
      bacteriochlorophyll (B) and the bacteriopheophytin (H) in the reaction center of
      the purple photosynthetic bacterium Rhodobacter sphaeroides as approximately 170
      +/- 30 cm-1. This is the first direct experimental determination of this
      parameter; it is within the range of values found in previously published
      calculations. The 1C3PEPS signal of the Qy band of the bacteriochlorophyll B
      shows that it is weakly coupled to nuclear motions of the bath, whereas the
      1C3PEPS signal of the Qy band of the bacteriopheophytin, H, shows that it is more
      strongly coupled to the bath, but has minimal inhomogeneous broadening. Our
      simulations capture the major features of the data with the theoretical framework
      developed in our group to separately calculate the response functions and
      population dynamics.

PMID- 17530797
TI  - Contrast variation SANS investigation of composition distributions in mixed
      surfactant micelles.
AB  - Small angle neutron scattering measurements have been performed on three systems
      (HFDeP-d5-C (N-1(1,1,2,2-tetrahydroperfluorodecanoyl)pyridinium-d5
      chloride)/C16PC in 63 mM NaCl; HFDeP-d5-C/C12PC in 200 mM NaCl, and as an example
      of an ideally mixed system, SDS/SDS-d25 in 200 mM NaCl) containing micelles
      formed in a binary mixture of surfactants, in order to investigate the
      composition distribution of the mixed micelles. The experimental data were
      collected varying the contrast between the average scattering length density of
      micelles and aqueous solvent by changing the H2O/D2O ratio. Analysis of data
      includes a model-independent approach--the indirect Fourier transformation method
      and direct modeling-simultaneous fit at all contrasts by the scattering from
      micelles of equal size and shape with composition distribution and an effective
      interaction. It has earlier been shown (Almgren, M.; Garamus, V. M. J. Phys.
      Chem. B 2005, 109, 11348) that for micelles of equal size, independent of the
      composition, and with negligible intermicellar interactions, the scattered
      intensity at zero angle varies quadratically with the contrast, with the minimum
      intensity at the nominal match point proportional to sigma2, the variance of the
      micelle composition distribution. Within the regular solution framework, the
      composition distribution and its variance are uniquely defined by the value of
      the interaction parameter and the micelle aggregation number. At 25 degrees C,
      the first system gave sigma = 0.37, corresponding to a broad, bimodal composition
      distribution, the second sigma = 0.22, a broad distribution with a shallow
      minimum at the midpoint. For SDS/SDS-d25, we found sigma = 0.006 +/- 0.030, which
      is a smaller value than that of the binominal composition distribution expected
      for an ideally mixed system.

PMID- 17530798
TI  - Impact of membrane immobilization on particle formation and trichloroethylene
      dechlorination for bimetallic Fe/Ni nanoparticles in cellulose acetate membranes.
AB  - The use of membrane immobilization to carry out the batch dechlorination of
      trichloroethylene (TCE) using bimetallic Fe/Ni (4:1, Fe to Ni) nanoparticles in
      cellulose acetate membranes is examined using modeling of transport phenomenon
      based on experimental results. Membranes are synthesized using both gelation and
      solvent evaporation techniques for phase inversion. The reduction of metal ions
      within cellulose acetate phase-inversion membranes was accomplished using sodium
      borohydride reduction to obtain up to 2 wt % total metals. Characterization of
      the mixed-matrix structure reveals a bimodal particle distribution ranging
      between 18 and 80 nm within the membrane cross section. The distribution is the
      result of changes in the morphology of the cellulose acetate support. The
      diffusivity and linear partitioning coefficient for the chlorinated organic were
      measured and are 2.0 x 10(-8) cm2.s-1 and 3.5 x 10(-2) L.g-1, respectively. An
      unsteady-state model for diffusion through a membrane with reaction was developed
      to predict experimental results with an error of only 7.2%. The error can be
      attributed to the lack of the model to account for loss of reactivity through pH
      effects, alloy effects (bimetallic ratio), and oxidation of nanoparticles.
      Simulations were run to vary the major transport variables, partitioning and
      diffusivity, and determine their impact on reaction kinetics. Of the two,
      diffusivity was less significant because it really only influences the time
      required for maximum TCE partitioning to the membrane to be achieved and has no
      effect on the limiting capacity of the membrane for TCE. Therefore, selection of
      an appropriate support material is crucial for development of highly reactive
      mixed-matrix membrane systems.

PMID- 17530799
TI  - Effect of cyclodextrin nanocavity confinement on the photophysics of a beta
      carboline analogue: a spectroscopic study.
AB  - Interaction of a beta-carboline based biologically active molecule, 3-acetyl-4
      oxo-6,7-dihydro-12H indolo-[2,3-a] quinolizine (AODIQ), with alpha-, beta-, and
      gamma-cyclodextrins (CDs) in aqueous solution has been studied using steady state
      and time-resolved fluorescence and steady-state fluorescence anisotropy
      techniques. Polarity dependent intramolecular charge transfer (ICT) process is
      responsible for the remarkable sensitivity of this biological fluorophore to the
      CD environments. Upon encapsulation, the CT fluorescence exhibits hypsochromic
      shift along with enhancements in the fluorescence yield, fluorescence anisotropy
      (r), and fluorescence lifetime. The reduction in the nonradiative deactivation
      rate of the fluorophore within the CD nanocavities leads to an increase in both
      fluorescence yield and lifetime. Among the three CDs, gamma-CD shows the most
      spectacular confinement effect. The results establish the formation of 1:1
      AODIQ:CD inclusion complexes in alpha- and beta-CDs. In aqueous gamma-CD
      solutions, however, depending on the concentration of the gamma-CD, formation of
      both 1:1 and 1:2 complexes have been revealed. Hydrodynamic radii of the 1:1 and
      1:2 probe-gamma-CD supramolecular complexes have also been determined.

PMID- 17530800
TI  - Enhancement of quadratic nonlinearity via multiple hydrogen-bonded supramolecular
      complex formation.
AB  - The formation and quadratic nonlinearity of a multiple hydrogen-bonded 1:1
      supramolecular complex 1.2 between the 2,6-diaminopyridine-based Lambda-shaped
      molecule, 1, and ferrocenyl barbituric acid, 2, in solution have been
      investigated by the hyper-Rayleigh scattering (HRS) and NMR techniques. A 6-fold
      increase in the molecular hyperpolarizability (beta) of the complex 1.2 over the
      sum of the molecular hyperpolarizabilities of the components 1 and 2 is seen.
      Such a significant enhancement in beta is attributed to the alignment of the
      molecular dipoles of 1 and 2 in the 2D plane leading to the creation of a large
      dipole moment in the plane of the supramolecular complex. Depolarized HRS
      experiments led to the determination of the in-plane polarization components of
      beta of the supramolecular complex 1.2. The component of beta in the direction of
      the dipole moment is large. This investigation exemplifies the role of multiple
      hydrogen bonds in stabilizing a 2D supramolecular architecture leading to a large
      enhancement of molecular nonlinearity.

PMID- 17530801
TI  - Fluorescence of single molecules in polymer films: sensitivity of blinking to
      local environment.
AB  - The single-molecule fluorescence blinking behavior of the organic dye Atto647N in
      various polymer matrixes such as Zeonex, PVK, and PVA as well as aqueous media
      was investigated. Fluorescence blinking with off-times in the millisecond to
      second time range is assigned to dye radical ions formed by photoinduced electron
      transfer reactions from or to the environment. In Zeonex and PVK, the measured
      off-time distributions show power law dependence, whereas, in PVA, no such
      dependence is observed. Rather, in this polymer, off-time distributions can be
      best fitted to monoexponential or stretched exponential functions. Furthermore,
      treatment of PVA samples to mild heating and low pressure greatly reduces the
      frequency of blinking events. We tentatively ascribe this to the removal of water
      pockets within the polymer film itself. Measurements of the dye immobilized in
      water in the presence of methylviologen, a strongly oxidizing agent, reveal
      simple exponential on- and off-time distributions. Thus, our data suggest that
      the blinking behavior of single organic molecules is sensitive to their immediate
      environment and, moreover, that fluorescence blinking on- and off-time
      distributions do not inherently and uniquely obey a power law.

PMID- 17530802
TI  - The reactivity of epoxides with lithium 2,2,6,6-tetramethylpiperidide in
      combination with organolithiums or grignard reagents.
AB  - The scope and limitations of lithium 2,2,6,6-tetramethylpiperidide (LTMP)
      modified reductive alkylation of epoxides is detailed. A variety of
      organolithiums are added to terminal and 2,2-disubstituted epoxides in the
      presence of LTMP to generate alkenes in a completely regio- and highly
      stereoselective manner. Arylated alkenes, dienes, allylsilanes, and enynes are
      accessed using this procedure. The methodology is applied in the synthesis of the
      roller leaf moth pheromone, (3E,5Z)-dodecadienyl acetate. The corresponding
      reaction without LTMP has also been examined, and a study using deuterated
      epoxides provides insight into the mechanism. In the presence of LTMP, Grignard
      reagents are also shown to produce E-alkenes directly from epoxides.

PMID- 17530803
TI  - Synthesis of aza-analogues of the glycosylated tyrosine portion of
      mannopeptimycin-E.
AB  - Two C4' amido disaccharide analogues of mannopeptimycin-E were synthesized via an
      iterative palladium glycosylation sequence. The stereoselective synthesis of the
      C4' acylated 1,4-alpha,alpha-manno,manno-amido disaccharide has been achieved in
      ten steps from a protected d-tyrosine. The path relies upon a regio- and
      diastereoselective palladium-catalyzed azide substitution reaction. The
      competence of the synthesis is demonstrated by the good overall yield (21%) from
      protected tyrosine.

PMID- 17530804
TI  - Synthesis of polyprenylated acylphloroglucinols using bridgehead lithiation: the
      total synthesis of racemic clusianone and a formal synthesis of racemic
      garsubellin A.
AB  - The synthesis of polyprenylated phloroglucinol natural products, including
      clusianone, nemorosone, and garsubellin A, was pursued by a strategy involving
      construction of a core bicyclo[3.3.1]nonanetrione structure and subsequent
      elaboration via organolithium intermediates. Appropriate bridged core structures
      were obtained through the cyclization of a suitably substituted cyclohexanone
      enol ether or enol silane with malonyl dichloride. Additional substituents were
      then introduced by means of regioselective lithiation reactions, including the
      generation of bridgehead enolates, thus enabling the total synthesis of
      clusianone and also of an advanced intermediate toward nemorosone. In the case of
      garsubellin A, an additional THF-like ring was elaborated by a biomimetic 5-exo
      tet cyclization of an enol ether (or enol) with a side-chain epoxide. This
      enabled a formal synthesis of racemic garsubellin A by accessing one of the late
      intermediates in the Danishefsky synthesis.

PMID- 17530805
TI  - Novel synthesis of 3,4-diaminobutanenitriles and 4-amino-2-butenenitriles from 2
      (cyanomethyl)aziridines through intermediate aziridinium salts: an experimental
      and theoretical approach.
AB  - 1-Arylmethyl-2-(cyanomethyl)aziridines were transformed into 4-(N,N
      bis(arylmethyl)amino)-3-(pyrrolidin-1-yl)butanenitriles and 4-(N,N
      bis(arylmethyl)amino)-2-butenenitriles via 4-(N,N-bis(arylmethyl)amino)-3
      bromobutanenitriles in high yields and purity. The key steps involve the
      unprecedented regiospecific ring opening of intermediate 2
      (cyanomethyl)aziridinium salts by bromide and pyrrolidine in acetonitrile,
      exclusively at the substituted aziridine carbon atom. The results were
      rationalized on the basis of ab initio calculations.

PMID- 17530806
TI  - Helical molecular duplex strands: multiple hydrogen-bond-mediated assembly of
      self-complementary oligomeric hydrazide derivatives.
AB  - Careful examination of the X-ray structure of a ditopic hydrazide derivative 7
      led to the concept that with malonyl groups as interhydrazide linkers hydrogen
      bonding-mediated molecular duplex strands might be obtained. Complexation studies
      between 7, 8, and 9 confirmed this hypothesis. Two quadruple hydrogen-bonded
      heterodimers formed, in which spectator repulsive secondary electrostatic
      interaction was found to play an important role in determining the stability of
      the complexes. Extensive studies on 1-4 indicated that the hydrogen-bonding mode
      could persist in longer oligomeric hydrazide derivatives with chain extension
      from monomer to tetramer. Molecular duplex strands via two to fourteen
      interstrand hydrogen bonds were obtained. In addition to affecting the stability
      of the duplex strands, spectator repulsive secondary electrostatic interaction
      also played an important role in determining dynamic behavior of the duplex
      strands as exemplified by variable temperature (1)H NMR experiments. IR studies
      confirmed stronger hydrogen bonding in the longer oligomers. The assemblies of 1
      4 on HOPG were also studied by STM technology. Molecular mechanical calculations
      further revealed double-helical structures for the longer oligomers. The results
      provide new opportunities for development of polymeric helical duplexes with well
      defined structures.

PMID- 17530808
TI  - Synthesis of thieno[2,3-d]pyrimidin-2-ylmethanamine combinatorial library with
      four diversity points.
AB  - The parallel solution-phase synthesis of more than 230 substituted thieno[2,3
      d]pyrimidin-2-ylmethanamines has been accomplished. This strategy is based on the
      cyclization of 2-aminothiophen-3-carboxylates with chloroacetonitrile to
      construct the thieno[2,3-d]pyrimidine core with two diversity points.
      Derivatization of the active chlorine and functionalization of C-4 position of
      the pyrimidine ring allow the introduction of other diversity points. The
      products containing ester groups at the 6-position of the thieno[2,3-d]pyrimidine
      were used in amide synthesis. Simple manual techniques for parallel reactions,
      coupled with simple purification procedures, gave highly pure final products. The
      scope and limitations of the approach are discussed.

PMID- 17530809
TI  - Ordered arrays of <100>-oriented silicon nanorods by CMOS-compatible block
      copolymer lithography.
AB  - Dense, ordered arrays of <100>-oriented Si nanorods with uniform aspect ratios up
      to 5:1 and a uniform diameter of 15 nm were fabricated by block copolymer
      lithography based on the inverse of the traditional cylindrical hole strategy and
      reactive ion etching. The reported approach combines control over diameter,
      orientation, and position of the nanorods and compatibility with complementary
      metal oxide semiconductor (CMOS) technology because no nonvolatile metals
      generating deep levels in silicon, such as gold or iron, are involved. The Si
      nanorod arrays exhibit the same degree of order as the block copolymer templates.

PMID- 17530810
TI  - SP1 as a novel scaffold building block for self-assembly nanofabrication of
      submicron enzymatic structures.
AB  - In this study, SP1, a ring-shaped highly stable homododecamer protein complex was
      utilized for the self-assembly of multiple domains in a predefined manner.
      Glucose oxidase (GOx) was fused in-frame to SP1 and expressed in Escherichia
      coli. Complexes where GOx encircled SP1 dodecamer were observed, and moreover,
      the enzymatic monomers self-assembled into active multienzyme nanotube particles
      containing hundreds of GOx molecules per tube. This work demonstrates the value
      of SP1 as a self-assembly scaffold.

PMID- 17530811
TI  - Ultrathin, responsive polymer click capsules.
AB  - We report a general click chemistry approach for the layer-by-layer assembly of
      ultrathin, polymer films on particles and the subsequent formation of polymer
      click capsules (CCs). Poly(acrylic acid) copolymers, synthesized with a minor
      component of either alkyne (PAA-Alk) or azide (PAA-Az) functionality, were
      alternately assembled on silica particles. The (PAA-Az/PAA-Alk)-coated particles
      were subsequently functionalized by exploiting the free alkyne click moieties
      present in the film upon exposure to an azide-modified rhodamine dye. Further,
      PAA CCs, obtained following removal of the silica particle template, were shown
      to exhibit pH-responsive behavior. This was demonstrated by reversible size
      changes of the CCs upon cycling between basic and acidic solutions. Polymer CCs
      are anticipated to find applications in various fields, including drug delivery
      and sensing.

PMID- 17530812
TI  - Simultaneous multicolor imaging of five different lymphatic basins using quantum
      dots.
AB  - Quantum dots can be used to perform multicolor images with high fluorescent
      intensity and are of a nanosize suitable for lymphatic imaging via direct
      interstitial injection. Here simultaneous multicolor in vivo wavelength-resolved
      spectral fluorescence lymphangiography is shown using five quantum dots with
      similar physical sizes but different emission spectra. This allows noninvasive
      and simultaneous visualization of five separate lymphatic flows draining and may
      have implications for predicting the route of cancer metastasis into the lymph
      nodes.

PMID- 17530813
TI  - Probing in situ the nucleation and growth of gold nanoparticles by small-angle X
      ray scattering.
AB  - We probe in situ by synchrotron SAXS/WAXS and UV-visible spectroscopy the
      nucleation and growth of gold nanoparticles. The use of a fast-mixing stopped
      flow device enables the assessment of the whole particle formation process with a
      200 ms time resolution. The number of particles, their size distribution, and the
      yield of the reaction is determined in real time through the quantitative
      analysis of the SAXS data on an absolute scale. Two ligands exhibit drastically
      different behaviors: when an alkanoic acid is used, a nucleation phase of 1 s is
      followed by a growth step whose rate is limited by the reaction of the monomers
      at the interface; on the other hand, when an alkylamine is used, the nucleation
      rate is increased by an order of magnitude, thus annealing growth by a lack of
      monomer and yielding R=1 nm particles in 2 s, as compared with R=3.7 nm in 12 s
      for the acid case.

PMID- 17530814
TI  - A reactive peptidic linker for self-assembling hybrid quantum dot-DNA
      bioconjugates.
AB  - Self-assembly of proteins, peptides, DNA, and other biomolecules to semiconductor
      quantum dots (QD) is an attractive bioconjugation route that can circumvent many
      of the problems associated with covalent chemistry and subsequent purification.
      Polyhistidine sequences have been shown to facilitate self-assembly of proteins
      and peptides to ZnS-overcoated CdSe QDs via complexation to unoccupied
      coordination metal sites on the nanocrystal surface. We describe the synthesis
      and characterization of a thiol-reactive hexahistidine peptidic linker that can
      be chemically attached to thiolated-DNA oligomers and mediate their self-assembly
      to CdSe-ZnS core-shell QDs. The self-assembly of hexahistidine-appended DNA to
      QDs is probed with gel electrophoresis and fluorescence resonance energy transfer
      techniques, and the results confirm high-affinity conjugate formation with
      control over the average molar ratio of DNA assembled per QD. To demonstrate the
      potential of this reactive peptide linker strategy, a prototype QD-DNA-dye
      molecular beacon is self-assembled and tested against both specific and
      nonspecific target DNAs. This conjugation route is potentially versatile, as
      altering the reactivity of the peptide linker may allow targeting of different
      functional groups such as amines and facilitate self-assembly of other
      nanoparticle-biomolecule structures.

PMID- 17530815
TI  - A polysaccharide carrier to effectively deliver native phosphodiester CpG DNA to
      antigen-presenting cells.
AB  - Oligodeoxynucleotides containing unmethylated CpG sequences (CpG DNAs) activate
      the vertebrate innate immune system via toll-like receptor 9 (TLR-9). Although
      CpG DNA is a promising immunotherapeutic agent, its short circulation time in
      biological fluids due to nuclease is the major drawback. This paper proposes that
      a natural polysaccharide called schizophyllan (SPG) can be used as an effective
      CpG DNA carrier because SPG can complex with CpG DNA and the resultant complex
      shows the nuclease resistance of the bound DNA. In order to increase cellular
      uptake in vitro, we chemically attached spermine, cholesterol, arginine octamer,
      or RGD peptide to SPG. The complexes made of the chemically modified SPG and CpG
      DNA having a phosphorothioate (PS) or phosphodiester (PO) backbone led to
      increased secretion of cytokines of about 4- to 15-fold, compared with the
      uncomplexed dose. Furthermore, when PO CpG DNA was complexed with unmodified SPG,
      the IL-12 level increased by almost 3- to 11-fold compared with the naked dose.
      The PO CpG DNA/unmodified SPG complex data suggested that unmodified SPG might
      effectively deliver PO in vivo due to the electrically neutral nature of
      unmodified SPG. When the complexed CpG DNAs were injected intraperitoneally, a
      large amount of IL-12 production was observed compared with the uncomplexed
      material. Both in vivo and vitro assays indicated that the SPG complex may be of
      use for CpG DNA therapy.

PMID- 17530816
TI  - Fourier transform analysis of chronoamperometric currents obtained during
      staircase voltammetric experiments.
AB  - We report a novel comprehensive Fourier transform electrochemical impedance
      spectroscopic (FTEIS) analysis method of a series of chronoamperometric currents
      obtained during staircase cyclic voltammetric (SCV) experiments. In our method,
      FTEIS analysis of a set of chronoamperometric currents recorded upon applying a
      series of small potential steps during an SCV experiment provides a complete
      description of an electron-transfer reaction at the electrode/electrolyte
      interface in forms of equivalent circuit elements. Conversion of the circuit
      elements thus obtained from the analysis allows electrode kinetic parameters
      including the electron-transfer rate constant, transfer coefficient, diffusion
      coefficient, and double layer capacitance as well as thermodynamic parameters
      such as the half-wave potential and the apparent number of electrons transferred
      to be determined. Theories for obtaining an ac admittance voltammogram, as well
      as both the thermodynamic and mass-transfer kinetic parameters thereof, from the
      SCV data have been developed and verified. A decided advantage of the method is
      that it provides completely self-contained information regarding an electron
      transfer reaction from a single pass of the SCV experiment.

PMID- 17530817
TI  - Selection of aptamers for molecular recognition and characterization of cancer
      cells.
AB  - In this paper, we describe a new way to generate molecular probes for specific
      recognition of cancer cells. Molecular medicine will require a large number of
      probes for molecular recognition and characterization of a variety of diseased
      cells. Aptamers, single-stranded DNA/RNA probes, are poised to become a chemist's
      antibody and have the potential to serve as molecular probes for a variety of
      biomedical applications. By applying newly developed cell-SELEX (cell-based
      systematic evolution of ligands by exponential enrichment) against whole living
      cells, panels of aptamers have been evolved from an initial DNA library to
      characterize target cells at the molecular level. Ramos cells, a B-cell lymphoma
      cell line, were used as target cells for the generation of effective molecular
      probes. By taking advantages of the repetitive and broad enrichment strategy, the
      selected aptamers could bind to target cells and other closely related cell lines
      in variant patterns with an equilibrium dissociation constant (Kd) in the
      nanomolar range. Some aptamers could also specifically recognize the target
      lymphoma cells mixed with normal human bone marrow aspirates. The cell-based
      SELEX is simple, fast, and robust. The strategies used here will be highly useful
      for aptamer selection against complex target samples in order to generate a large
      number of aptamers in a variety of biomedical and biotechnological applications,
      paving the way for molecular diagnosis, therapy, and biomarker discovery.

PMID- 17530818
TI  - Room-temperature bonding for plastic high-pressure microfluidic chips.
AB  - A generic method for the rapid, reproducible, and robust bonding of microfluidic
      chips fabricated from plastics has been developed and optimized. One of the
      bonding surfaces is exposed to solvent vapor prior to bringing the mating parts
      into contact and applying a load. Nanoindentation measurements performed by
      atomic force microscopy show that a reversible material softening occurs upon
      exposure to solvent vapor. Subsequent exposure of the bonded chip to UV light
      then strengthens the bond between mating parts and increases the burst pressure
      by 50% due to partial cross-linking and chain scission reactions as measured by
      size exclusion chromatography-multiangle light scattering (SEC-MALS). Performing
      all steps of this procedure at room temperature eliminates channel distortion
      observed during thermal bonding and affords channels with highly uniform cross
      sectional dimensions. Our technique enables chips resistant to pressures as high
      as 34.6 MPa.

PMID- 17530819
TI  - Investigation of anion retention and cation exclusion effects for several C18
      stationary phases.
AB  - When mobile-phase salt content is increased, cationic analytes often show
      increased retention. This effect is generally attributed to chaotropic or ion
      pairing effects. However, a cation exclusion mechanism could explain the same
      effects. In this study, experimental conditions were manipulated to enhance
      cation exclusion effects and reduce chaotropic/ion pairing effects by using (1)
      low ionic strength mobile phases to reduce electrostatic screening, (2) a buffer
      anion (dihydrogen phosphate) that exhibits minimal chaotropic/ion pairing
      effects, and (3) columns that show evidence of a weak positive charge. Urea was
      used as neutral void marker and glycinamide (in protonated form) as cationic void
      marker. It was assumed the difference in retention volumes between void markers
      would reflect an "excluded volume", inaccessible to cationic analytes. As ionic
      strength was lowered, it appeared as much as 80% of the pore volume became
      inaccessible to the glycinamide cation at the lowest ionic strength tested (1.4
      mM). Three model cationic analytes showed retention loss approximately
      proportional to the excluded volume as ionic strength was decreased. This
      suggests that, under certain conditions, cation exclusion may become the dominant
      mechanism in mediating the retention of cationic analytes as the mobile-phase
      salt content is varied.

PMID- 17530820
TI  - Tailored quartz pins for high-density microsensor array fabrication.
AB  - We report on a quartz pin that can be interfaced easily to existing pin printers.
      The new pin surface can be reversibly derivatized using silanization chemistry,
      allowing one to reliably print a wide variety of liquid solutions. Feature sizes
      as small as 9 microm can be produced with the new pin, allowing one to readily
      create microarrays with a feature density approaching 10(6) spots/cm2.

PMID- 17530821
TI  - Electrochemical DNA biosensor based on conducting polyaniline nanotube array.
AB  - Most of the recent developments in ultrasensitive detection of nucleic acid are
      based on the gold nanoparticles and carbon nanotubes as a medium of signal
      amplification. Here, we present an ultrasensitive electrochemical nucleic acid
      biosensor using the conducting polyaniline (PANI) nanotube array as the signal
      enhancement element. The PANI nanotube array of a highly organized structure was
      fabricated under a well-controlled nanoscale dimension on the graphite electrode
      using a thin nanoporous layer as a template, and 21-mer oligonucleotide probes
      were immobilized on these PANI nanotubes. In comparison with gold nanoparticle-
      or carbon nanotube-based DNA biosensors, our PANI nanotube array-based DNA
      biosensor could achieve similar sensitivity without catalytic enhancement,
      purification, or end-opening processing. The electrochemical results showed that
      the conducting PANI nanotube array had a signal enhancement capability, allowing
      the DNA biosensor to readily detect the target oligonucleotide at a concentration
      as low as 1.0 fM (approximately 300 zmol of target molecules). In addition, this
      biosensor demonstrated good capability of differentiating the perfect matched
      target oligonucleotide from one-nucleotide mismatched oligonucleotides even at a
      concentration of 37.59 fM. This detection specificity indicates that this
      biosensor could be applied to single-nucleotide polymorphism analysis and single
      mutation detection.

PMID- 17530822
TI  - The structure of the hydrated electron. Part 1. Magnetic resonance of internally
      trapping water anions: a density functional theory study.
AB  - Density functional theory is used to rationalize magnetic parameters of hydrated
      electron trapped in alkaline glasses as observed using electron paramagnetic
      resonance (EPR) and electron spin echo envelope modulation (ESEEM)
      spectroscopies. To this end, model water cluster anions (n=4-8 and n=20, 24) that
      localize the electron internally are examined. It is shown that hyperfine
      coupling tensors of H/D nuclei in the water molecules are defined mainly by the
      cavity size and the coordination number of the electron; the water molecules in
      the second solvation shell play a relatively minor role. An idealized model of
      the hydrated electron (that is usually attributed to L. Kevan) in which six
      hydroxyl groups arranged in an octahedral pattern point toward the common center
      is shown to provide the closest match to the experimental parameters, such as
      isotropic and anisotropic hyperfine coupling constants for the protons (estimated
      from ESEEM), the second moment of the EPR spectra, and the radius of gyration.
      The salient feature is the significant transfer (10-20%) of spin density into the
      frontal O 2p orbitals of water molecules. Spin bond polarization involving these
      oxygen orbitals accounts for small, negative hyperfine coupling constants for
      protons in hydroxyl groups that form the electron-trapping cavity. In Part 2,
      these results are generalized for more realistic geometries of core anions
      obtained using a dynamic one-electron mixed quantum/classical molecular dynamics
      model.

PMID- 17530823
TI  - The structure of the hydrated electron. Part 2. A mixed quantum/classical
      molecular dynamics embedded cluster density functional theory: single-excitation
      configuration interaction study.
AB  - Adiabatic mixed quantum/classical (MQC) molecular dynamics (MD) simulations were
      used to generate snapshots of the hydrated electron in liquid water at 300 K.
      Water cluster anions that include two complete solvation shells centered on the
      hydrated electron were extracted from the MQC MD simulations and embedded in a
      roughly 18 Ax18 Ax18 A matrix of fractional point charges designed to represent
      the rest of the solvent. Density functional theory (DFT) with the Becke-Lee-Yang
      Parr functional and single-excitation configuration interaction (CIS) methods
      were then applied to these embedded clusters. The salient feature of these hybrid
      DFT(CIS)/MQC MD calculations is significant transfer (approximately 18%) of the
      excess electron's charge density into the 2p orbitals of oxygen atoms in OH
      groups forming the solvation cavity. We used the results of these calculations to
      examine the structure of the singly occupied and the lower unoccupied molecular
      orbitals, the density of states, the absorption spectra in the visible and
      ultraviolet, the hyperfine coupling (hfcc) tensors, and the infrared (IR) and
      Raman spectra of these embedded water cluster anions. The calculated hfcc tensors
      were used to compute electron paramagnetic resonance (EPR) and electron spin echo
      envelope modulation (ESEEM) spectra for the hydrated electron that compared
      favorably to the experimental spectra of trapped electrons in alkaline ice. The
      calculated vibrational spectra of the hydrated electron are consistent with the
      red-shifted bending and stretching frequencies observed in resonance Raman
      experiments. In addition to reproducing the visible/near IR absorption spectrum,
      the hybrid DFT model also accounts for the hydrated electron's 190-nm absorption
      band in the ultraviolet. Thus, our study suggests that to explain several
      important experimentally observed properties of the hydrated electron, many
      electron effects must be accounted for: one-electron models that do not allow for
      mixing of the excess electron density with the frontier orbitals of the first
      shell solvent molecules cannot explain the observed magnetic, vibrational, and
      electronic properties of this species. Despite the need for multielectron effects
      to explain these important properties, the ensemble-averaged radial wavefunctions
      and energetics of the highest occupied and three lowest unoccupied orbitals of
      the hydrated electrons in our hybrid model are close to the s- and p-like states
      obtained in one-electron models. Thus, one-electron models can provide a
      remarkably good approximation to the multielectron picture of the hydrated
      electron for many applications; indeed, the two approaches appear to be
      complementary.

PMID- 17530824
TI  - Ab initio/DFT and AIM studies on dual hydrogen-bonded complexes of 2
      hydroxypyridine/2-pyridone tautomerism.
AB  - The second-order Moller-Plesset (MP2) and density functional theory (DFT)
      calculations have been carried out to investigate the structures and stabilities
      of hydrogen (H-) bonded 2-hydroxypyridine (2HP)/2-pyridone (2PY) dimeric forms as
      well as 2HP-2PY complexes. The results on single-point counterpoise (CP)
      correction of these complexes were compared against CP-optimized correction. The
      nature of the intermolecular contacts in the sense of normal H-bond or blue
      shifting H-bond was determined on the basis of harmonic vibrational, atom-in
      molecule (AIM), and natural bond orbital (NBO) analysis. A blue-shifting C-H...N
      H-bond was found and NBO analysis revealed a slight decrease in the population of
      the contacting sigmaC-H* antibonding orbital as the primary reason of the C-H
      contraction. Good correlations have been established between the interaction
      energies and the H-bond distances versus other characteristic H-bond parameters.

PMID- 17530825
TI  - Interactions between the chloride anion and aromatic molecules: infrared spectra
      of the Cl- -C6H5CH3, Cl- -C6H5NH2 and Cl- -C6H5OH complexes.
AB  - The Cl- -C6H5CH3*Ar, Cl- -C6H5NH2*Ar, and Cl- -C6H5OH*Ar anion complexes are
      investigated using infrared photodissociation spectroscopy and ab initio
      calculations at the MP2/aug-cc-pVDZ level. The results indicate that for Cl- 
      C6H5NH2 and Cl- -C6H5OH, the Cl- anion is attached to the substituent group by a
      single near-linear hydrogen bond. For Cl--C6H5CH3, the Cl- is attached to an
      ortho-hydrogen atom on the aromatic ring and to a hydrogen atom on the methyl
      group by a weaker hydrogen bond. The principal spectroscopic consequence of the
      hydrogen-bonding interaction in the three complexes is a red-shift and intensity
      increase for the CH, NH, and OH stretching modes. Complexities in the infrared
      spectra in the region of the hydrogen-bonded XH stretch band are associated with
      Fermi resonances between the hydrogen-stretching vibrational modes and bending
      overtone and combination levels. There are notable correlations between the
      vibrational red-shift, the elongation of the H-bonded XH group, and the proton
      affinity of the aromatic molecule's conjugate base.

PMID- 17530826
TI  - The Green's function density functional tight-binding (gDFTB) method for
      molecular electronic conduction.
AB  - A review is presented of the nonequilibrium Green's function (NEGF) method
      "gDFTB" for evaluating elastic and inelastic conduction through single molecules
      employing the density functional tight-binding (DFTB) electronic structure
      method. This focuses on the possible advantages that DFTB implementations of NEGF
      have over conventional methods based on density functional theory, including not
      only the ability to treat large irregular metal-molecule junctions with high
      nonequilibrium thermal distributions but perhaps also the ability to treat
      dispersive forces, bond breakage, and open-shell systems and to avoid large band
      lineup errors. New results are presented indicating that DFTB provides a useful
      depiction of simple gold-thiol interactions. Symmetry is implemented in DFTB, and
      the advantages it brings in terms of large savings of computational resources
      with significant increase in numerical stability are described. The power of DFTB
      is then harnessed to allow the use of gDFTB as a real-time tool to discover the
      nature of the forces that control inelastic charge transport through molecules
      and the role of molecular symmetry in determining both elastic and inelastic
      transport. Future directions for the development of the method are discussed.

PMID- 17530827
TI  - Spectroscopic evidence for the formation of helical structures in gas-phase short
      peptide chains.
AB  - Aminoisobutyric acid (Aib) is a synthetic amino acid known to favor the formation
      of 3(10) helical structures in condensed phases, namely, crystals. The intrinsic
      character of these helicogenic properties has been investigated on the Ac-Aib-Phe
      Aib-NH2 molecule under isolated conditions, namely, in the gas phase, both
      experimentally by double-resonance IR/UV spectroscopy and theoretically by
      quantum chemistry. A convergent set of evidence, based on energetic, IR, and UV
      spectroscopic data as well as on analogies with the similar peptide Ac-Ala-Phe
      Ala-NH2 previously studied, enables us to conclude the formation of an incipient
      310 helix in these isolated systems.

PMID- 17530828
TI  - Conformation dependence of the CalphaDalpha stretch mode in peptides. 1. Isolated
      alanine peptide structures.
AB  - Ab initio normal mode calculations have been performed on isolated alanine di-
      through octa-(i.e., blocked) peptides in uniform alphaR, beta, and polyproline II
      conformations to determine how the CalphaDalpha stretch mode, which has been
      proposed as a possible determinant of the varphi,psi conformation at the Calpha
      atom (Mirkin, N. G.; Krimm, S. J. Phys. Chem. A 2004, 108, 10923), depends on
      conformation and sequence length. This set of frequencies, including results on
      some kinked structures, demonstrates that such a discrimination is likely to be
      possible through experimental observations of peptides synthesized with
      successive deuteration at the Halpha sites, on the basis of at least three
      properties: the values of the frequency at the first residue, the pattern of
      successive frequency differences, and the frequency differences between the first
      and last residues.

PMID- 17530829
TI  - Theoretical prediction of the S1-S0 internal conversion of 6-cyanoazulene.
AB  - Ab initio complete active-space self-consistent field (CASSCF) and second-order
      Multireference Moller-Plesset perturbation (MRMP2) calculations were performed to
      examine the S1-S0 internal conversion of 6-cyanoazulene (6CNAZ). The azulene
      skeletons of 6CNAZ in S0 and S1 have features that resemble those of azulene. The
      stable geometry in S0 is characterized by (i) a C2v structure, (ii) an aromatic
      bond-equalized structure in which all the peripheral skeletal bond distances
      resemble an aromatic CC bond distance, and (iii) a single bond character of the
      transannular bond. The stable geometry in S1 is characterized by a nonaromatic
      C2v structure. Contrary to similarities of the stable geometries in S0 and S1
      between 6CNAZ and azulene, the conical intersection (S1/S0-CIX) of 6CNAZ is
      different from that of azulene. The S1/S0-CIX of 6CNAZ takes a planar structure,
      whereas that of azulene takes a nonplanar structure in the seven-membered ring
      (Amatatsu, Y.; Komura, K. J. Chem. Phys. 2006, 125, 174311/1-8). On the basis of
      those computational findings, we predict the photochemical behavior of 6CNAZ in
      the S1-S0 internal conversion.

PMID- 17530830
TI  - Spin state selective detection of single quantum transitions using multiple
      quantum coherence: simplifying the analyses of complex NMR spectra.
AB  - NMR spectra of molecules oriented in liquid-crystalline matrix provide
      information on the structure and orientation of the molecules. Thermotropic
      liquid crystals used as an orienting media result in the spectra of spins that
      are generally strongly coupled. The number of allowed transitions increases
      rapidly with the increase in the number of interacting spins. Furthermore, the
      number of single quantum transitions required for analysis is highly redundant.
      In the present study, we have demonstrated that it is possible to separate the
      subspectra of a homonuclear dipolar coupled spin system on the basis of the spin
      states of the coupled heteronuclei by multiple quantum (MQ)-single quantum (SQ)
      correlation experiments. This significantly reduces the number of redundant
      transitions, thereby simplifying the analysis of the complex spectrum. The
      methodology has been demonstrated on the doubly 13C labeled acetonitrile aligned
      in the liquid-crystal matrix and has been applied to analyze the complex spectrum
      of an oriented six spin system.

PMID- 17530831
TI  - Study of NH stretching vibrations in small ammonia clusters by infrared
      spectroscopy in He droplets and ab initio calculations.
AB  - Infrared spectra of the NH stretching vibrations of (NH3)n clusters (n = 2-4)
      have been obtained using the helium droplet isolation technique and first
      principles electronic structure anharmonic calculations. The measured spectra
      exhibit well-resolved bands, which have been assigned to the nu1, nu3, and 2nu4
      modes of the ammonia fragments in the clusters. The formation of a hydrogen bond
      in ammonia dimers leads to an increase of the infrared intensity by about a
      factor of 4. In the larger clusters the infrared intensity per hydrogen bond is
      close to that found in dimers and approaches the value in the NH3 crystal. The
      intensity of the 2nu4 overtone band in the trimer and tetramer increases by a
      factor of 10 relative to that in the monomer and dimer, and is comparable to the
      intensity of the nu1 and nu3 fundamental bands in larger clusters. This indicates
      the onset of the strong anharmonic coupling of the 2nu4 and nu1 modes in larger
      clusters. The experimental assignments are compared to the ones obtained from
      first principles electronic structure anharmonic calculations for the dimer and
      trimer clusters. The anharmonic calculations were performed at the Moller-Plesset
      (MP2) level of electronic structure theory and were based on a second-order
      perturbative evaluation of rovibrational parameters and their effects on the
      vibrational spectra and average structures. In general, there is excellent (<20
      cm(-1)) agreement between the experimentally measured band origins for the N-H
      stretching frequencies and the calculated anharmonic vibrational frequencies.
      However, the calculations were found to overestimate the infrared intensities in
      clusters by about a factor of 4.

PMID- 17530832
TI  - A combined experimental and theoretical study of uranium polyhydrides with new
      evidence for the large complex UH4(H2)6.
AB  - Several monouranium and diuranium polyhydride molecules were investigated using
      quantum chemical methods. The infrared spectra of uranium and hydrogen reaction
      products in condensed neon and pure hydrogen were measured and compared with
      previous argon matrix frequencies. The calculated molecular structures and
      vibrational frequencies were used to identify the species present in the matrix.
      Major new absorptions were observed and compared with the previous argon matrix
      study. Spectroscopic evidence was obtained for the novel complex, UH4(H2)6, which
      has potential interest as a metal hydride with a large number of hydrogen atoms
      bound to uranium. Our calculations show that the series of complexes
      UH4(H2)1,2,4,6 are stable.

PMID- 17530833
TI  - Initial excited-state structural dynamics of thymine are coincident with the
      expected photochemical dynamics.
AB  - To explore the excited-state structural dynamics of thymine, a DNA nucleobase, we
      measured the resonance Raman spectra of thymine in aqueous solution at
      wavelengths throughout the lowest-energy absorption band. Self-consistent
      analysis of the resulting resonance Raman excitation profiles and absorption
      spectrum using a time-dependent wave packet formalism yielded the excited-state
      structural dynamics. The photochemically relevant C=C stretching and C-H
      deformation vibrational modes were found to exhibit maximum resonance Raman
      intensity and structural change upon photoexcitation for thymine, suggesting that
      the initial dynamics of thymine lie along the photochemical reaction coordinate.

PMID- 17530834
TI  - Glycine in an electronically excited state: ab initio electronic structure and
      dynamical calculations.
AB  - The goal of this study is to explore the photochemical processes following
      optical excitation of the glycine molecule into its two low-lying excited states.
      We employed electronic structure methods at various levels to map the PES of the
      ground state and the two low-lying excited states of glycine. It follows from our
      calculations that the photochemistry of glycine can be regarded as a combination
      of photochemical behavior of amines and carboxylic acid. The first channel
      (connected to the presence of amino group) results in ultrafast decay, while the
      channels characteristic for the carboxylic group occur on a longer time scale.
      Dynamical calculations provided the branching ratio for these channels. We also
      addressed the question whether conformationally dependent photochemistry can be
      observed for glycine. While electronic structure calculations favor this
      possibility, the ab initio multiple spawning (AIMS) calculations showed only
      minor relevance of the reaction path resulting in conformationally dependent
      dynamics.

PMID- 17530835
TI  - Ultrafast photoinduced electron transfer in directly linked porphyrin-ferrocene
      dyads.
AB  - The ultrafast electron transfer occurring upon Soret excitation of three new
      porphyrin-ferrocene (XP-Fc) dyads has been studied by femtosecond up-conversion
      and pump-probe techniques. In the XP-Fc dyads (XP-Fcs) designed in this study,
      the ferrocene moiety is covalently bonded to the meso positions of 3,5-di-tert
      butylphenyl zinc porphyrin (BPZnP-Fc), pentafluorophenyl zinc porphyrin (FPZnP
      Fc), and 3,5-di-tert-butylphenyl free-base porphyrin (BPH2P-Fc). Charge
      separation and recombination in the XP-Fcs were confirmed by transient absorption
      spectra, and the lifetimes of the charge-separated states were estimated from the
      decay rate of the porphyrin radical anion band to be approximately 20 ps. The
      charge-separation rates of the XP-Fcs were found to be >10(13) s-1 from the S2
      state and 6.3x10(12) s-1 from the S1 state. Charge separation from the S2 state
      was particularly efficient for BPZnP-Fc, whereas the main reaction pathway was
      from the S1 state for BPH2P-Fc. Charge separation from the S2 and S1 states
      occurred at virtually the same rate in benzene and tetrahydrofuran and was much
      faster than their solvation times. Analysis of these results using semiquantum
      Marcus theory indicates that the magnitude of the electronic-tunneling matrix
      element is rather large and far outside the range of nonadiabatic approximation.
      The pump-probe data show the presence of vibrational coherence during the
      reactions, suggesting that wavepacket dynamics on the adiabatic potential energy
      surface might regulate the ultrafast reactions.

PMID- 17530836
TI  - Wave function delocalization and large-amplitude vibrations of helium on
      corrugated aromatic microsurfaces: tetracene.He and pentacene.He van der Waals
      complexes.
AB  - We report accurate quantum three-dimensional calculations of highly excited
      intermolecular vibrational states of the van der Waals (vdW) complexes
      tetracene.He and pentacene.He in the S1 excited electronic state. The aromatic
      molecules were taken to be rigid and the intermolecular potential energy surfaces
      (IPESs) were modeled as a sum of atom-atom Lennard-Jones pair potentials. The
      IPESs are corrugated in the direction of the long (x) axis of the aromatic
      molecules, due to the presence of the symmetrically equivalent global double
      minimum for tetracene.He, and a triple minimum (central global minimum and two
      equivalent local minima) for pentacene.He, on each side of the aromatic plane.
      Both IPESs have two additional minor equivalent local minima further away from
      the center of the molecule. The vdW vibrational states analyzed in this work
      cover about 80% of the well depths of the IPESs. The mode coupling is generally
      weak for those states whose out-of-plane (z) mode is unexcited. However, the z
      mode fundamental is strongly coupled to the short-axis (y) in-plane mode, so that
      the pure z-mode excitation could not be identified. The He atom exhibits large in
      plane spatial delocalizaton already in the ground vdW vibrational state, which
      increases rapidly upon the excitation of the in-plane x and y modes, with little
      hindrance by the corrugation of the aromatic microsurfaces. For the vdW
      vibrational energies considered, the He atom spatial delocalization reaches
      Deltax and Deltay values of approximately 5 and 4 A, respectively, and is limited
      only by the finite size of the aromatic substrates. Side-crossing delocalization
      of the wave functions on both sides of the molecular plane is found at excitation
      energies >30 cm(-1), giving rise to the energy splittings of the pairs of states
      symmetric/antisymmetric with respect to the aromatic plane; the splittings show
      strong vdW vibrational mode specificity.

PMID- 17530837
TI  - Nonenantioselectivity property of human deoxycytidine kinase explained by
      structures of the enzyme in complex with L- and D-nucleosides.
AB  - Biological molecules are predominantly enantioselective. Yet currently two
      nucleoside analogue prodrugs (3TC and FTC) with opposite chirality compared to
      physiological nucleosides are clinically approved for the treatment of HIV
      infections. These prodrugs require conversion to their triphosphorylated forms to
      achieve pharmacological activity. The first step in the activation of these
      agents is catalyzed by human deoxycytidine kinase (dCK). This enzyme possesses
      the ability to phosphorylate nucleosides of the unnatural L-chirality. To
      understand the molecular basis for the nonenantioselectivity of dCK, we solved
      the crystal structures of the enzyme in complex with the L-enantiomer and of its
      physiological substrate deoxycytidine and with the L-nucleoside analogue FTC.
      These were compared to a structure solved with D-dC. Our results highlight
      structural adjustments imposed on the L-nucleosides and properties of the enzyme
      endowing it with the ability to phosphorylate substrates with nonphysiological
      chirality. This work reveals the molecular basis for the activation of L
      nucleosides by dCK.

PMID- 17530838
TI  - Discovery of potent, selective, orally bioavailable stearoyl-CoA desaturase 1
      inhibitors.
AB  - Stearoyl-CoA desaturase 1 (SCD1) catalyzes the committed step in the biosynthesis
      of monounsaturated fatty acids from saturated, long-chain fatty acids. Studies
      with SCD1 knockout mice have established that these animals are lean and
      protected from leptin deficiency-induced and diet-induced obesity, with greater
      whole body insulin sensitivity than wild-type animals. In this work, we have
      discovered a series of potent, selective, orally bioavailable SCD1 inhibitors
      based on a known pyridazine carboxamide template. The representative lead
      inhibitor 28c also demonstrates excellent cellular activity in blocking the
      conversion of saturated long-chain fatty acid-CoAs (LCFA-CoAs) to monounsaturated
      LCFA-CoAs in HepG2 cells.

PMID- 17530839
TI  - Automatic perception of organic molecules based on essential structural
      information.
AB  - Format conversion is very common in structure preparation in molecular modeling
      studies. Unfortunately, format conversion cannot always be executed precisely. We
      have developed an automatic method, called I-interpret (available on-line at
      http://www.sioc-ccbg.ac.cn/software/I-interpret/), for interpreting the chemical
      structure of a given organic molecule merely from its essential structural
      information, including element identities and three-dimensional coordinates of
      its component atoms. I-interpret uses standard geometrical parameters of organic
      molecules in atom/bond-type assignment. A series of elaborate considerations are
      arranged in a logical sequence for this purpose. I-interpret was tested on a set
      of 179 small organic molecules from the Protein Data Bank and a set of 1990
      organic molecules from the NCI diversity set. On both sets, it achieved a success
      rate of over 95% in interpreting the correct chemical structures, outperforming
      other programs under our evaluation. I-interpret also provides users some
      optional functions, which makes it more flexible and powerful in practice. It may
      serve as a valuable tool for processing chemical structures in molecular
      modeling.

PMID- 17530840
TI  - Indium hydroxides, oxyhydroxides, and oxides nanocrystals series.
AB  - Indium hydroxides, oxyhydroxides, and oxides are important n-type semiconductors
      and have wide applications in material fields. In this Article, a series of
      In(OH)(3) and InOOH nanocrystals with different structures and morphologies, such
      as nanocubes, nanorods, multipods, and nanoparticles, have been synthesized
      selectively through a liquid-phase reaction, by adjusting the alkalinity and
      polarity of the solvent. It is found that InOOH multipods are in the orthorhombic
      phase and their arms grow along nonequivalent faces. Cubic and hexagonal
      In(2)O(3) can be obtained from In(OH)(3) and InOOH, respectively, while size and
      morphology can be maintained to a certain extent. Gas sensors were fabricated by
      using In(2)O(3), and a device based on the multipods shows the best responses to
      ethanol vapor. XRD, TEM, HRTEM, SEM, and SAED have been used to characterize
      these nanocrystals. This work provides a preliminary investigation into the
      structural-based gas-sensing properties of these nanocrystals.

PMID- 17530841
TI  - BN-analogues of vinylidene transition metal complexes: the borylnitrene isomer.
AB  - Density functional computations using the BP86 functional within the resolution
      of-identity approximation and polarized triple-zeta basis sets are employed for
      the study of the three isoelectronic (CO)(4)FeL (L = CCH(2) (5), BNH(2) (6),
      NBH(2) (7)) as well as (CO)(4)Fe(NBcat) (9) (cat = catecholato) complexes. In all
      complexes 5-7, the ligand L prefers the equatorial position of a pseudo trigonal
      bipyramid. The borylnitrene complex 7 has a linear Fe-N-B arrangement; its Fe-L
      bond dissociation energy is similar to that of the vinylidene complex 5 and only
      slightly lower than that of 6. Nonetheless, 7 is less stable thermodynamically
      than 6 by 40 kcal mol(-1). Complexes of type 7 are expected to be reactive on the
      basis of the following findings: the HOMO-LUMO energy gap is small, the
      rearrangement from 7 to 6 via an iminoborane intermediate involves barriers of 15
      and 28 kcal mol(-1), and the dissociation of a CO molecule to give
      (CO)(3)FeNBH(2) is only slightly endergonic (+7 kcal mol(-1) at 298.15 K). The
      catecholate bridge in 9 results in significant changes: the bipyramidal complex
      is no longer a minimum, but an isocycanato complex is obtained instead
      computationally.

PMID- 17530842
TI  - Syntheses and structures of ytterbium(II) hydride and hydroxide complexes:
      similarities and differences with their calcium analogues.
AB  - The Yb(II) hydride complex (DIPP-nacnac)YbH x THF (3-Yb, DIPP-nacnac =
      CH{(CMe)(2,6-iPr(2)C(6)H(3)N)}(2)) was prepared by a mild metathesis reaction of
      (DIPP-nacnac)Yb[N(SiMe(3))(2)].THF with PhSiH(3). 3-Yb crystallizes as a dimer
      with bridging hydride ions, and its geometry is similar to that of the analogue
      calcium hydride complex (3-Ca). 3-Yb is well soluble in benzene and remarkably
      stable in solution at room temperature. Ligand exchange to the homoleptic Yb(II)
      complexes takes place at higher temperatures (3-Yb is less stable than the
      analogue 3-Ca). The soluble hydride complexes 3-Ca and 3-Yb are catalysts for the
      hydrosilylation of 1,1-diphenylethylene, but differences in the product
      distributions are observed. Slow hydrolysis of (DIPP-nacnac)Yb[N(SiMe(3))(2)].THF
      gave reduction of water and unidentified Yb(III) complexes. Fast hydrolysis at
      low temperature, however, resulted in the first Yb(II) hydroxide complex, (DIPP
      nacnac)Yb(OH) x THF (4-Yb, 20% yield), which is a dimer with bridging hydroxide
      ions in the solid state. The crystal structure is isomorphous to that of the
      calcium analogue 4-Ca. 4-Yb is well soluble in benzene and considerably more
      stable against ligand exchange and formation of homoleptic species than 3-Yb.

PMID- 17530843
TI  - Bis(alpha-diimine)nickel complexes: molecular and electronic structure of three
      members of the electron-transfer series [Ni(L)(2)](z)() (z = 0, 1+, 2+) (L = 2
      Phenyl-1,4-bis(isopropyl)-1,4-diazabutadiene). A combined experimental and
      theoretical study.
AB  - From the reaction of Ni(COD)(2) (COD = cyclooctadiene) in dry diethylether with 2
      equiv of 2-phenyl-1,4-bis(isopropyl)-1,4-diazabutadiene (L(Ox))(0) under an Ar
      atmosphere, dark red, diamagnetic microcrystals of [Ni(II)(L*)(2)] (1) were
      obtained where (L*)(1-) represents the pi radical anion of neutral (L(Ox))(0) and
      (L(Red))(2-) is the closed shell, doubly reduced form of (L(Ox))(0). Oxidation of
      1 with 1 equiv of ferrocenium hexafluorophosphate in CH(2)Cl(2) yields a
      paramagnetic (S = 1/2), dark violet precipitate of [Ni(I)(L(Ox))(2)](PF(6)) (2)
      which represents an oxidatively induced reduction of the central nickel ion. From
      the same reaction but with 2 equiv of [Fc](PF(6)) in CH(2)Cl(2), light green
      crystals of [Ni(II)(L(Ox))(2)(FPF(5))](PF(6)) (3) (S = 1) were obtained. If the
      same reaction was carried out in tetrahydrofuran, crystals of
      [Ni(II)(L(Ox))(2)(THF)(FPF(5))](PF(6)) x THF (4) (S = 1) were obtained. Compounds
      1, 2, 3, and 4 were structurally characterized by X-ray crystallography: 1 and 2
      contain a tetrahedral neutral complex and a tetrahedral monocation, respectively,
      whereas 3 contains the five-coordinate cation [Ni(II)(L(Ox))(2)(FPF(5))](+) with
      a weakly coordinated PF(6)(-) anion and in 4 the six-coordinate monocation
      [Ni(II)(L(Ox))(2)(THF)(FPF(5))](+) is present. The electro- and magnetochemistry
      of 1-4 has been investigated by cyclic voltammetry and SQUID measurements. UV-vis
      and EPR spectroscopic data for all compounds are reported. The experimental
      results have been confirmed by broken symmetry DFT calculations of
      [Ni(II)(L*)(2)](0), [Ni(I)(L(Ox))(2)](+), and [Ni(II)(L(Ox))(2)](2+) in
      comparison with calculations of the corresponding Zn complexes:
      [Zn(II)((t)L(Ox))(2)](2+), [Zn(II)((t)L(Ox))((t)L*)](+), [Zn(II)((t)L*)(2)](0),
      and [Zn(II)((t)L*)((t)L(Red))](-) where ((t)L(Ox))(0) represents the neutral
      ligand 1,4-di-tert-butyl-1,4-diaza-1,3-butadiene and ((t)L*)(1-) and
      ((t)L(Red))(2-) are the corresponding one- and two-electron reduced forms. It is
      clearly established that the electronic structures of both paramagnetic
      monocations [Ni(I)(L(Ox))(2)](+) (S = 1/2) and [Zn(II)((t)L(Ox))((t)(L*)](+) (S =
      1/2) are different.

PMID- 17530844
TI  - Elucidation of the solution structure and water-exchange mechanism of
      paramagnetic [Fe(II)(edta)(H(2)O)](2-).
AB  - The lability and structural dynamics of [Fe(II)(edta)(H(2)O)](2-) (edta =
      ethylenediaminetetraacetate) in aqueous solution strongly depend on solvent
      interactions. To study the solution structure and water-exchange mechanism, (1)H,
      (13)C, and (17)O NMR techniques were applied. The water-exchange reaction was
      studied through the paramagnetic effect of the complex on the relaxation rate of
      the (17)O nucleus of the bulk water. In addition to variable-temperature
      experiments, high-pressure NMR techniques were applied to elucidate the intimate
      nature of the water-exchange mechanism. The water molecule in the seventh
      coordination site of the edta complex is strongly labilized, as shown by the
      water-exchange rate constant of (2.7 +/- 0.1) x 106 s(-1) at 298.2 K and ambient
      pressure. The activation parameters DeltaH(not equal), DeltaS(not equal), and
      DeltaV(not equal) were found to be 43.2 +/- 0.5 kJ mol(-1), +23 +/- 2 J K(-1)
      mol(-1), and +8.6 +/- 0.4 cm(3) mol(-1), respectively, in line with a
      dissociatively activated interchange (Id) mechanism. The scalar coupling constant
      (A/h) for the Fe(II)-O interaction was found to be 10.4 MHz, slightly larger than
      the value A/h = 9.4 MHz for this interaction in the hexa-aqua Fe(II) complex. The
      solution structure and dynamics of [Fe(II)(edta)(H(2)O)](2-) were clarified by
      (1)H and (13)C NMR experiments. The complex undergoes a Delta,Lambda
      isomerization process with interconversion of in-plane (IP) and out-of-plane (OP)
      positions. Acetate scrambling was also found in an NMR study of the corresponding
      NO complex, [Fe(III)(edta)(NO(-))](2-).

PMID- 17530845
TI  - Transition metal-carbon complexes. A theoretical study.
AB  - The equilibrium geometries and bond dissociation energies of 16VE and 18VE
      complexes of ruthenium and iron with a naked carbon ligand are reported using
      density functional theory at the BP86/TZ2P level. Bond energies were also
      calculated at CCSD(T) using TZ2P quality basis sets. The calculations of
      [Cl2(PMe3)2Ru(C)] (1Ru), [Cl2(PMe3)2Fe(C)] (1Fe), [(CO)2(PMe3)2Ru(C)] (2Ru),
      [(CO)2(PMe3)2Fe(C)] (2Fe), [(CO)4Ru(C)] (3Ru), and [(CO)4Fe(C)] (3Fe) show that
      1Ru has a very strong Ru-C bond which is stronger than the Fe-C bond in 1Fe. The
      metal-carbon bonds in the 18VE complexes 2Ru-3Fe are weaker than those in the
      16VE species. Calculations of the related carbonyl complexes [(PMe3)2Cl2Ru(CO)]
      (4Ru), [(PMe3)2Cl2Fe(CO)] (4Fe), [(PMe3)2Ru(CO)3] (5Ru), [(PMe3)2Fe(CO)3] (5Fe),
      [Ru(CO)5] (6Ru), and [Fe(CO)5] (6Fe) show that the metal-CO bonds are much weaker
      than the metal-C bonds. The 18VE iron complexes have a larger BDE than the 18VE
      ruthenium complexes, while the opposite trend is calculated for the 16VE
      compounds. Charge and energy decomposition analyses (EDA) have been carried out
      for the calculated compounds. The Ru-C and Fe-C bonds in 1Ru and 1Fe are best
      described in terms of two electron-sharing bonds with sigma and pi symmetry and
      one donor-acceptor pi bond. The bonding situation in the 18 VE complexes 2Ru-3Fe
      is better described in terms of closed shell donor-acceptor interactions in
      accordance with the Dewar-Chatt-Duncanson model. The bonding analysis clearly
      shows that the 16VE carbon complexes 1Ru and 1Fe are much more strongly
      stabilized by metal-C sigma interactions than the 18VE complexes which is
      probably the reason why the substituted homologue of 1Ru could become isolated.
      The EDA calculations show that the nature of the TM-C and TM-CO binding
      interactions resembles each other. The absolute values for the energy terms which
      contribute to Delta(Eint) are much larger for the carbon complexes than for the
      carbonyl complexes, but the relative strengths of the energy terms are not very
      different from each other. The pi bonding contribution to the orbital
      interactions in the carbon complexes is always stronger than sigma bonding. There
      is no particular bonding component which is responsible for the reversal of the
      relative bond dissociation energies of the Ru and Fe complexes when one goes from
      the 16VE complexes to the 18VE species. That the 18 VE compounds have longer and
      weaker TM-C and TM-CO bonds than the respective 16 VE compounds holds for all
      complexes. This is because the LUMO in the 16 VE species is a sigma-antibonding
      orbital which becomes occupied in the 18 VE species.

PMID- 17530846
TI  - Supramolecular chemistry approach to the design of a high-resolution sensor array
      for multianion detection in water.
AB  - Reliable sensing of structurally similar anions in water is a difficult problem,
      and analytical tests and sensor devices for reliable sensing of multiple anions
      are very rare. This study describes a method for fabrication of simple
      colorimetric array-based assays for aqueous anion solutions, including complex
      analytes encountered in real-life applications. On the fundamental level, this
      method shows how the discriminatory capacity of sensor arrays utilizing pattern
      recognition operating in multianalyte environments may be dramatically improved
      by employing two key features. The synergy between the sensor and hydrogel host
      resembles the cooperative effects of an apoenzyme and cofactor: the host hydrogel
      helps extract the target anions from the bulk analyte while stripping the solvate
      molecules off the anions. In addition, the supramolecular studies of the affinity
      and selectivity of the potential sensors for target analytes allow for
      constructing an array predesigned for a particular analyte. To illustrate both
      aspects, an eight-sensor array utilizing colorimetric sensor materials showing
      selectivity for fluoride and pyrophosphate while displaying significant cross
      reactivity for other anions such as carboxylates, phosphate, or chloride was used
      to differentiate between 10 anions. The quantitative analyses were also performed
      to show that the eight-sensor array was found to operate across 4 orders of
      magnitude concentrations (0.20-360 ppm; 10 microM to 20 mM). The applicability of
      this approach was demonstrated by analyzing several toothpaste brands. The
      toothpastes are complex analytes comprising both known and unknown anions in
      various concentrations. The fluoride-selective yet cross-reactive array is shown
      to utilize the fluoride content as the main differentiating factor while using
      the remaining anionic components for further differentiation between toothpaste
      brands.

PMID- 17530847
TI  - Indirect ortho functionalization of substituted toluenes through ortho
      olefination of N,N-dimethylbenzylamines tuned by the acidity of reaction
      conditions.
AB  - Highly regioselective olefination of substituted N,N-dimethylbenzylamines was
      developed by tuning the acidity of reaction conditions based on analysis of their
      features. The ortho-functionalized N,N-dimethylbenzylamines were further
      transformed into 3-(2'-tolyl)propanoic acid and its derivatives under mild
      conditions. These two transformations could be combined into one pot, and 3-(2'
      tolyl)propanoic acid and its derivatives were obtained in moderate to good
      yields. Mechanistic studies indicated that electrophilic attack on the phenyl
      ring by the Pd(II) ion assisted by the N,N-dimethylaminomethyl group was a key
      step during this catalytic transformation, which was controlled by the acidity of
      the reaction conditions.

PMID- 17530848
TI  - Cyclization cascade of allenyl azides: a dual mechanism.
AB  - A density functional theory based computational approach to describing the
      mechanistic course of the allene azide cycloaddition cascade sequence has been
      developed. The results of these calculations permit characterization of key
      reactive intermediates (diradicals and/or indolidenes) and explain the different
      behaviors observed in the experimental studies between conjugated and
      nonconjugated species. Furthermore, computational analysis of certain
      intermediates offer insight into issues of regioselectivity and stereoselectivity
      in cases where different reaction channels are in competition, suggesting
      suitable substitutions to achieve a single regioisomer in the indole synthesis
      via azide-allene cyclization.

PMID- 17530849
TI  - Regioselectivity and diasteroselectivity in Pt(II)-mediated "green" catalytic
      epoxidation of terminal alkenes with hydrogen peroxide: mechanistic insight into
      a peculiar substrate selectivity.
AB  - Recently developed electron-poor Pt(II) catalyst 1 with the "green" oxidant 35%
      hydrogen peroxide displays high activity and complete substrate selectivity in
      the epoxidation of terminal alkenes because of stringent steric and electronic
      requirements. In the presence of isolated dienes bearing terminal and internal
      double bonds, epoxidation is completely regioselective toward the production of
      terminal epoxides. Insight into the mechanism is gained by means of a reaction
      progress kinetic analysis approach that underlines the peculiar role of 1 in
      activating both the alkene and H2O2 in the rate-determining step providing a rare
      example of nucleophilic oxidation of alkenes by H2O2.

PMID- 17530850
TI  - Antibiofouling polymer-coated gold nanoparticles as a contrast agent for in vivo
      X-ray computed tomography imaging.
AB  - Current computed tomography (CT) contrast agents such as iodine-based compounds
      have several limitations, including short imaging times due to rapid renal
      clearance, renal toxicity, and vascular permeation. Here, we describe a new CT
      contrast agent based on gold nanoparticles (GNPs) that overcomes these
      limitations. Because gold has a higher atomic number and X-ray absorption
      coefficient than iodine, we expected that GNPs can be used as CT contrast agents.
      We prepared uniform GNPs ( approximately 30 nm in diameter) by general reduction
      of HAuCl4 by boiling with sodium citrate. The resulting GNPs were coated with
      polyethylene glycol (PEG) to impart antibiofouling properties, which extends
      their lifetime in the bloodstream. Measurement of the X-ray absorption
      coefficient in vitro revealed that the attenuation of PEG-coated GNPs is 5.7
      times higher than that of the current iodine-based CT contrast agent, Ultravist.
      Furthermore, when injected intravenously into rats, the PEG-coated GNPs had a
      much longer blood circulation time (>4 h) than Ultravist (<10 min). Consequently,
      CT images of rats using PEG-coated GNPs showed a clear delineation of cardiac
      ventricles and great vessels. On the other hand, relatively high levels of GNPs
      accumulated in the spleen and liver, which contain phagocytic cells. Intravenous
      injection of PEG-coated GNPs into hepatoma-bearing rats resulted in a high
      contrast ( approximately 2-fold) between hepatoma and normal liver tissue on CT
      images. These results suggest that PEG-coated GNPs can be useful as a CT contrast
      agent for a blood pool and hepatoma imaging.

PMID- 17530851
TI  - Organocatalytic asymmetric reaction cascade to substituted cyclohexylamines.

PMID- 17530852
TI  - Long-range structural restraints in spin-labeled proteins probed by solid-state
      nuclear magnetic resonance spectroscopy.

PMID- 17530853
TI  - Synthesis of structural analogues of the oxidized sites in the xanthine
      oxidoreductase enzyme family.

PMID- 17530854
TI  - The active form of Chlamydia trachomatis ribonucleotide reductase R2 protein
      contains a heterodinuclear Mn(IV)/Fe(III) cluster with S = 1 ground state.

PMID- 17530855
TI  - Addition of difluoromethyl radicals to glycals: a new route to alpha-CF2-D
      glycosides.
AB  - The synthesis of synthetically useful alpha-CF2-glycosides by radical addition of
      ethyl bromodifluoroacetate onto 2-benzyloxyglycals is described. The methodology
      provides an access to alpha-O-glycoside mimics and, potentially, to valuable
      alpha-O-glycoconjugate analogues.

PMID- 17530856
TI  - Templated synthesis of desymmetrized [2]catenanes with excellent translational
      selectivity.
AB  - Desymmetrized [2]catenanes were synthesized and shown to exhibit excellent
      translational selectivity. The templated synthesis takes effect from the
      formation of pseudorotaxanes between pi-rich crown ethers and a pi-deficient
      pyromellitic (PmI) unit, followed by macrocyclization around the crown ethers
      with the creation of a bipyridinium (BPy) unit. The crown ethers preferably
      encircle the BPy unit in the resulting [2]catenanes in both solution and the
      solid state, as indicated by various spectroscopic analyses.

PMID- 17530857
TI  - Antiallergic effect of milk fermented with lactic acid bacteria in a murine
      animal model.
AB  - The objective of this study was to assess the antiallergic effect of fermented
      milk prepared, respectively, with Streptococcus thermophilus MC, Lactobacillus
      acidophilus B, Lactobacillus bulgaricus Lb, L. bulgaricus 448, and
      Bifidobacterium longum B6. Female BALB/c mice fed fermented milk were immunized
      intraperitoneally with ovalbumin (OVA)/complete Freund's adjuvant (CFA) to
      evaluate the immune response by observing the secretion of cytokines IL-2, IL-4,
      and IFN-gamma and serum antibody IgE. The results showed that supplementation
      with lactic acid bacteria fermented milk did not significantly change the IL-2
      spontaneous and OVA-stimulated secretions of splenocytes. However, both
      spontaneous and OVA-stimulated secretions of splenocytes from mice fed lactic
      acid bacteria fermented milk showed significantly (P < 0.05) lower levels of IL-4
      (Th2 cytokine) than those from OVA/CFA-immunized mice fed non-fermented milk
      (OVA/CFA-milk group). The spontaneous secretion of IFN-gamma (Th1 cytokine) by
      splenocytes from mice fed L. bulgaricus 448 or L. bulgaricus Lb fermented milk
      significantly increased as compared to that from the OVA/CFA-milk group. The
      results showed that the ratios of IFN-gamma to IL-4 of both spontaneous and OVA
      stimulated secretions in splenocytes from mice fed lactic acid bacteria fermented
      milk increased significantly as compared to that of PBS- or OVA/CFA-milk groups.
      The serum levels of OVA-specific IgE in fermented milk fed groups, especially the
      group fed S. thermophilus MC fermented milk, were significantly lower than those
      in the OVA/CFA-milk group through a 6 week feeding experiment. The results showed
      that milk fermented with lactic acid bacteria demonstrated in vivo antiallergic
      effects on OVA/CFA-immunized mice via increasing the secretion ratio of IFN
      gamma/IL-4 (Th1/Th2) by splenocytes and decreasing the serum level of OVA
      specific IgE.

PMID- 17530858
TI  - Sweet-like off-flavor in Aglianico del Vulture wine: ethyl phenylacetate as the
      mainly involved compound.
AB  - Interest in high-quality and peculiar products is a recent trend in the
      enological field; for this reason, production of wines from autochthonous vine
      varieties is requested by consumers. Aglianico wine from the Italian region
      "Basilicata" is an example of a promising product strictly connected to the
      territory; nevertheless, it is affected by a frequent sweet-like off-flavor. In
      this study the compositional cause of this off-flavor was investigated by SPME-GC
      olfactometry, SPME-GC-MS, and sensory tests. Ethyl phenylacetate (EPhA) was found
      to be the compound mainly responsible, and its sensory threshold was determined
      near 73 microg/L; products with the odorant concentration near and up to these
      values were always recognized as significantly different from the other wines and
      were often far from wine technical pleasantness; besides EPhA gave to the wines a
      strong honey-like character. Some preliminary hypotheses about its mechanism of
      formation (shikimate pathway) are presented in this study: these hypotheses could
      explain the correlation between EPhA and volatile phenols that was found by both
      sensory tests and GC quantitative analysis of wines affected by different levels
      of defect.

PMID- 17530859
TI  - Effect of oxidation on in vitro digestibility of skeletal muscle myofibrillar
      proteins.
AB  - The objective of this study was to investigate the effect of chemical oxidation
      on myofibrillar protein digestibility. Myofibrils were prepared from pig M.
      longissimus dorsi and oxidized by a hydroxyl radical generating system. Oxidative
      modifications of proteins were assessed by the carbonyl content, surface
      hydrophobicity, electrophoresis, and immunoblotting. Oxidized or nonoxidized
      myofibrillar proteins were then exposed to proteases of the digestive tract
      (pepsin, trypsin, and alpha-chymotrypsin). Results showed a direct and
      quantitative relationship between protein damages by hydroxyl radical and loss of
      protein digestibility.

PMID- 17530860
TI  - Hydroxytyrosol-rich olive mill wastewater extract protects brain cells in vitro
      and ex vivo.
AB  - Elevated oxidative and nitrosative stress both impair the integrity and
      functioning of brain tissue, especially in aging. As long-term intake of plant
      foods rich in antioxidant phenolics, such as extra virgin olive oil, positively
      modulates surrogate markers of many human pathological alterations, the interest
      in cheap and abundant sources of such phenolics is rapidly growing. Olive mill
      wastewater is particularly rich in hydroxytyrosol, an o-diphenol with powerful
      antioxidant, anti-inflammatory, and antithrombotic activities. Due to the
      deleterious effect of oxidative stress on brain cell survival, the efficacy of a
      hydroxytyrosol-rich extract to attenuate Fe2+- and nitric oxide (NO)-induced
      cytotoxicity in murine-dissociated brain cells was investigated. The addition of
      either Fe2+ or SNP (an NO donor) caused both a severe loss of cellular ATP and a
      markedly depolarized mitochondrial membrane potential. Preincubation with
      hydroxytyrosol significantly attenuated the cytotoxic effect of both stressors,
      although with different efficiencies. Mice feeding studies were performed to
      assess the brain bioactivity of hydroxytyrosol ex vivo. Subchronic, but not
      acute, administration of 100 mg of hydroxytyrosol per kilogram body weight for 12
      days enhanced resistance of dissociated brain cells to oxidative stress, as shown
      by reduced basal and stress-induced lipid peroxidation. Also, basal mitochondrial
      membrane potential was moderately hyperpolarized (P < 0.05), an effect suggestive
      of cytoprotection. In synthesis, the ex vivo data provide the first evidence of
      neuroprotective effects of oral hydroxytyrosol intake. KEYWORDS: Hydroxytyrosol;
      olive mill wastewater; dissociated brain cells; oxidative stress; brain;
      Mediterranean diet.

PMID- 17530861
TI  - Efficient synthesis of (+/-)-4-methyloctanoic acid, aggregation pheromone of
      rhinoceros beetles of the genus Oryctes (Coleoptera: Dynastidae, Scarabaeidae).
AB  - (+/-)-4-Methyloctanoic acid and its ethyl ester are aggregation pheromones of
      many rhinoceros beetles of the genus Oryctes and are investigated for the control
      of these pests by olfactory trapping. A simple, economical, and high-yield (>50%)
      synthesis of (+/-)-4-methyloctanoic acid and its ethyl ester is presented
      starting from n-hexanal. The key step in this sequence is an orthoester Claisen
      rearrangement for the elongation of the carbon chain by two.

PMID- 17530862
TI  - Characterization of the key aroma compounds in apricots (Prunus armeniaca) by
      application of the molecular sensory science concept.
AB  - An aroma extract dilution analysis applied on an aroma distillate prepared from
      fresh apricots revealed (R)-gamma-decalactone, (E)-beta-damascenone, delta
      decalactone, and (R/S)-linalool with the highest flavor dilution (FD) factors
      among the 26 odor-active compounds identified. On the basis of quantitative
      measurements performed by application of stable isotope dilution assays, followed
      by a calculation of odor activity values (OAVs), beta-ionone, (Z)-1,5-octadien-3
      one, gamma-decalactone, (E,Z)-2,6-nonadienal, linalool, and acetaldehyde appeared
      with OAVs >100, whereas in particular certain lactones, often associated with an
      apricot aroma note, such as gamma-undecalactone, gamma-nonalactone, and delta
      decalactone, showed very low OAVs (<5). An aroma recombinate prepared by mixing
      the 18 most important odorants in concentrations as they occurred in the fresh
      fruits showed an overall aroma very similar to that of apricots. Omission
      experiments indicated that previously unknown constituents of apricots, such as
      (E,Z)-2,6-nonadienal or (Z)-1,5-octadien-3-one, are key contributors to the
      apricot aroma.

PMID- 17530863
TI  - Orientation and motion of tryptophan interfacial anchors in membrane-spanning
      peptides.
AB  - The tryptophans of integral membrane proteins have been suggested to play
      specific roles as "interfacial anchors", based on their preference for a location
      near the lipid head groups. Still, the underlying mechanism behind this behavior
      remains unclear. NMR experiments can provide an important tool to study this
      interaction in an actual bilayer environment. Here solid-state deuterium nuclear
      magnetic resonance was used to study the tryptophans in membrane-spanning model
      peptides from the WALP family (acetyl-GWW(LA)nWWA-ethanolamide with n = 5 and
      6.5) in samples of mechanically aligned dimyristoylphosphatidylcholine (DMPC)
      bilayers. The data indicate that the tryptophans near the C-terminal end of the
      peptide display a significantly different behavior from those near the N
      terminus. This is reflected prominently in a large difference in the motion
      experienced by the indoles at either end of the peptide, highlighting the
      directionality of the helix. Nevertheless, our observations indicate high levels
      of motional freedom for all tryptophans in these membrane spanning domains that
      exceed the dynamics for the helix itself. These observations signify that steric
      and dynamic features of the polypeptide context modulate the tryptophan anchoring
      in the membrane interface. Measurements of WALP19 in the ether-linked DMPC
      analogue ditetradecylphosphatidylcholine (missing the lipid carbonyls) show very
      similar Trp dynamics and suggest similar orientations for some or all of the
      tryptophans. This suggests that the lipid acyl chain carbonyls play at most a
      minor role in the anchoring interaction between these Trp residues and the DMPC
      interfacial region.

PMID- 17530865
TI  - Non-native aggregation of alpha-chymotrypsinogen occurs through nucleation and
      growth with competing nucleus sizes and negative activation energies.
AB  - The kinetics and structural transitions of non-native aggregation of alpha
      chymotrypsinogen (aCgn) were investigated over a wide range of temperature and
      initial protein concentration at pH 3.5, where high molecular weight aggregates
      remained soluble throughout the reaction. A comparison of thermodynamic, kinetic,
      and spectroscopic data shows that aggregation under non-native-favoring
      conditions proceeds through a molten globule unfolded monomer state, with a
      nucleation and growth mechanism. Formation of irreversible aggregates and
      conversion to beta-sheet secondary structures occur simultaneously without
      detectable intermediates, suggesting that beta-sheet formation may be a
      commitment step during the nucleation and growth stages. Analysis of the kinetics
      using a Lumry-Eyring with nucleated polymerization (LENP) model provides the
      predominant nucleus size and the product of the intrinsic nucleation and
      intrinsic growth time scales at each state point. We find that the nucleus size
      depends on both temperature and protein concentration, and in some cases there is
      competition between two distinct nucleus sizes. The observed rate coefficient
      (kobs) for aggregation displays a maximum as a function of temperature because of
      the competition between folding-unfolding thermodynamics and the intrinsic growth
      and nucleation rates; the latter contribution has a large, negative activation
      enthalpy that dominates kobs at elevated temperatures. Temperature-jump
      experiments reveal that aggregates depolymerize at high temperatures, indicating
      that they are lower in enthalpy than the free monomer. Overall, the results
      suggest more generally that non-native aggregation may proceed through more than
      one nucleus size and that intrinsic kinetics of nucleation and growth may have
      significant entropic barriers.

PMID- 17530864
TI  - Pathways for intracellular generation of oxidants and tyrosine nitration by a
      macrophage cell line.
AB  - Two transformed murine macrophage cell lines (RAW 264.7 ATCC TIB-71 and CRL-2278)
      were examined for oxidant production at various times following activation by
      using a set of fluorescence and ESR-active probes. Stimulation with a soluble
      agonist or activation with bacterial lipopolysaccharide plus gamma-interferon
      caused only very small initial increases in O2 consumption above basal rates;
      however, at 2-4 h post-activation, respiration increased to 2-3-fold and remained
      at these elevated levels over the subsequent lifetime of the cell (20-30 h).
      Oxidation reactions were confined primarily within the cell, as was demonstrated
      by using phagocytosable dichlorodihydrofluorescein-conjugated latex beads and
      cyclic hydroxylamines with differing membrane permeabilities. From the intrinsic
      reactivities of these probes and the time course of their oxidations, one infers
      the induction of apparent peroxidase activity beginning at approximately 2 h post
      activation coinciding with the increase in overall respiratory rate; this
      acquired capability was accompanied by accumulation of a stable horseradish
      peroxidase-reactive oxidant, presumably H2O2, in the extracellular medium.
      Nitrite ion rapidly accumulated in the extracellular medium over a period of 5-8
      h post-activation in both cell lines, indicating the presence of active nitric
      oxide synthase (iNOS) during that period. Prostaglandin endoperoxide H synthase
      (COX-2) activity was detected at 15-20 h post-activation by the use of a
      sensitive peroxide assay in conjunction with a COX-2 specific inhibitor (DuP
      697). Superoxide formation was detected by reaction with hydroethidine within the
      first hour following activation, but not thereafter. Consistent with the absence
      of significant respiratory stimulation, the amount of O2*- formed was very small;
      comparative reactions of cyclic hydroxylamine probes indicated that virtually
      none of the O2*- was discharged into the external medium. Myeloperoxidase (MPO)
      activity was probed at various times post-activation by using fluorescein
      conjugated polyacrylamide beads, which efficiently trap MPO-generated HOCl in
      neutrophils to give stable chlorofluorescein products. However, chlorination of
      the dye was not detected under any conditions in RAW cells, virtually precluding
      MPO involvement in their intracellular reactions. This same probe was used to
      determine changes in intraphagosomal pH, which increased slowly from
      approximately 6.5 to approximately 8.2 over a 20 h post-phagocytosis period. The
      cumulative data suggest that activation is followed by sequential induction of an
      endogenous peroxidase, iNOS, and COX-2, with NADPH oxidase-derived O2*- playing a
      minimal role in the direct generation of intracellular oxidants. To account for
      reported observations of intracellular tyrosine nitration late in the life cycles
      of macrophages, we propose a novel mechanism wherein iNOS-generated NO2- is used
      by COX-2 to produce NO2* as a terminal microbicidal oxidant and nitrating agent.

PMID- 17530866
TI  - Speciation of human plasma high-density lipoprotein (HDL): HDL stability and
      apolipoprotein A-I partitioning.
AB  - The distribution of apolipoprotein (apo) A-I between human high-density
      lipoproteins (HDL) and water is an important component of reverse cholesterol
      transport and the atheroprotective effects of HDL. Chaotropic perturbation (CP)
      with guanidinium chloride (Gdm-Cl) reveals HDL instability by inducing the
      unfolding and transfer of apo A-I but not apo A-II into the aqueous phase while
      forming larger apo A-I deficient HDL-like particles and small amounts of
      cholesteryl ester-rich microemulsions (CERMs). Our kinetic and hydrodynamic
      studies of the CP of HDL species separated according to size and density show
      that (1) CP mediated an increase in HDL size, which involves quasi-fusion of
      surface and core lipids, and release of lipid-free apo A-I (these processes
      correlate linearly), (2) >94% of the HDL lipids remain with an apo A-I deficient
      particle, (3) apo A-II remains associated with a very stable HDL-like particle
      even at high levels of Gdm-Cl, and (4) apo A-I unfolding and transfer from HDL to
      water vary among HDL subfractions with the larger and more buoyant species
      exhibiting greater stability. Our data indicate that apo A-I's on small HDL (HDL
      S) are highly dynamic and, relative to apo A-I on the larger more mature HDL,
      partition more readily into the aqueous phase, where they initiate the formation
      of new HDL species. Our data suggest that the greater instability of HDL-S
      generates free apo A-I and an apo A-I deficient HDL-S that readily fuses with the
      more stable HDL-L. Thus, the presence of HDL-L drives the CP remodeling of HDL to
      an equilibrium with even larger HDL-L and more lipid-free apo A-I than with
      either HDL-L or HDL-S alone. Moreover, according to dilution studies of HDL in 3
      M Gdm-Cl, CP of HDL fits a model of apo A-I partitioning between HDL
      phospholipids and water that is controlled by the principal of opposing forces.
      These findings suggest that the size and relative amount of HDL lipid determine
      the HDL stability and the fraction of apo A-I that partitions into the aqueous
      phase where it is destined for interaction with ABCA1 transporters, thereby
      initiating reverse cholesterol transport or, alternatively, renal clearance.

PMID- 17530867
TI  - The P-glycoprotein (ABCB1) linker domain encodes high-affinity binding sequences
      to alpha- and beta-tubulins.
AB  - P-Glycoprotein (or ABCB1) has been shown to cause multidrug resistance in tumor
      cell lines selected with lipophilic anticancer drugs. ABCB1 encodes a duplicated
      molecule with two hydrophobic and hydrophilic domains linked by a highly charged
      region of approximately 90 amino acids, the "linker domain" with as yet unknown
      function(s). In this report, we demonstrate a role for this domain in binding to
      other cellular proteins. Using overlapping hexapeptides that encode the entire
      amino acid sequence of the linker domain of human ABCB1, we show a direct and
      specific binding between sequences in the linker domain and several intracellular
      proteins. Three different polypeptide sequences [617EKGIYFKLVTM627 (LDS617-627),
      657SRSSLIRKRSTRRSVRGSQA676 (LDS657-676), and 693PVSFWRIMKLNLT705 (LDS693-705)] in
      the linker domain interacted tightly with several proteins with apparent
      molecular masses of approximately 80, 57, and 30 kDa. Interestingly, only the 57
      kDa protein (or P57) interacted with all three different sequences of the linker
      domain. Purification and partial N-terminal amino acid sequencing of P57 showed
      that it encodes the N-terminal amino acids of alpha- and beta-tubulins. The
      identity of the P57 interacting protein as tubulins was further confirmed by
      Western blotting using monoclonal antibodies to alpha- and beta-tubulin. Taken
      together, the results of this study provide the first evidence for ABCB1 protein
      interaction mediated by sequences in the linker domain. These findings are likely
      to provide further insight into the functions of ABCB1 in normal and drug
      resistant tumor cells.

PMID- 17530868
TI  - A predictive approach of the influence of the operating parameters on the size of
      polymer particles synthesized in a simplified microfluidic system.
AB  - Monodisperse and size-controlled spherical polymer particles were synthesized by
      in situ photopolymerization of O/W monomer emulsions. Monomer droplets were
      produced without surfactant or pretreatment at a needle tip in a simplified
      axisymmetric microfluidic device. The effect of the viscosity of the continuous
      phase on the particle size was studied. The system operated in the dripping mode,
      at a low Reynolds number. A dimensionless master curve describes the particle
      diameter as a function of the needle inner diameter as well as velocity and
      viscosity ratios of continuous and dispersed phases. An empirical law predicts
      the particle size. The normalized particle diameter depends upon the ratio of the
      capillary numbers of continuous and dispersed phases with an exponent equal to 
      0.22.

PMID- 17530869
TI  - Controlling the electrophoretic mobility of single-walled carbon nanotubes: a
      comparison of theory and experiment.
AB  - The electrophoretic mobilities of single-walled carbon nanotubes (SWNTs) in
      agarose gels subjected to negatively charged covalent functionalization and
      noncovalent anionic surfactant adsorption are compared using a simplified
      hydrodynamic model. Net charges are calculated on the basis of estimated friction
      coefficients for cylindrical rodlike particles. The effects of functionalization
      with negatively charged 4-hydroxybenzene diazonium and anionic sodium cholate are
      quantified and compared with model predictions. The adsorption of Na+ counterions
      into the nonionic surfactant layer adsorbed on SWNTs (Triton-X-405) is shown to
      induce a positive charge and reverse the mobility under select conditions. This
      effect has not been identified or quantified for nanoparticle systems and may be
      important in the processing of these systems.

PMID- 17530870
TI  - Chitosan derivatives as biosorbents for basic dyes.
AB  - The scope of this study was to prepare and evaluate chitosan derivatives as
      biosorbents for basic dyes. This was achieved by grafting poly (acrylic acid) and
      poly (acrylamide) through persulfate induced free radical initiated
      polymerization processes and covalent cross-linking of the prepared materials.
      Remacryl Red TGL was used as the cationic dye. Equilibrium sorption experiments
      were carried out at different pH and initial dye concentration values. The
      experimental equilibrium data for each adsorbent-dye system were successfully
      fitted to the Langmuir, Freundlich and pH-dependent Langmuir-Freundlich sorption
      isotherms. Thermodynamic parameters of the adsorption process such as DeltaG
      degrees, DeltaH degrees, and DeltaS degrees were calculated. The negative values
      of free energy reflected the spontaneous nature of adsorption. The typical
      dependence of dye uptake on temperature and the kinetics of adsorption indicated
      the process to be chemisorption. The grafting modifications greatly enhanced the
      adsorption performance of the biosorbents, especially in the case of powdered
      cross-linked chitosan grafted with acrylic acid, which exhibited a maximum
      adsorption capacity equal to 1.068 mmol/g. Kinetic studies also revealed a
      significant improvement of sorption rates by the modifications. Diffusion
      coefficients of the dye molecule were determined to be of the order 10(-13) - 10(
      12) m2/s. Furthermore, desorption experiments affirmed the regenerative
      capability of the loaded material.

PMID- 17530872
TI  - Surfactant adsorption on solid surfaces: recognition between heterogeneous
      surfaces and adsorbed surfactant aggregates.
AB  - We study the possibility of the recognition of surface heterogeneities with
      surfactant adsorption by performing Monte Carlo simulations. It is found that
      when each patch size of a heterogeneous surface is capable of being commensurate
      with the size of aggregates adsorbed on the constituent homogeneous surfaces, the
      adsorption isotherm of the system will display both adsorption characteristics
      for each homogeneous surface. Otherwise, one or more adsorption characteristics
      will be spoiled or destroyed. Therefore, the adsorption isotherm of surfactants
      on a heterogeneous surface provides a signal of recognition.

PMID- 17530871
TI  - Enhanced stability and bioconjugation of photo-cross-linked polystyrene-shell, Au
      core nanoparticles.
AB  - Encapsulating Au nanoparticles within a shell of photo-cross-linked block
      copolymer surfactant dramatically improves the physical and chemical stability of
      the nanoparticles, particularly when they are applied as bioconjugates. Photo
      cross-linkable block copolymer amphiphiles [polystyrene-co-poly(4-vinyl
      benzophenone)]-block-poly(acrylic acid) [(PS-co-PVBP)-b-PAA] and [poly(styrene)
      co-poly(4-vinyl benzophenone)]-block-poly(ethylene oxide) [(PS-co-PVBP)-b-PEO]
      were assembled around Au nanoparticles ranging from 12 to 108 nm in diameter. UV
      irradiation cross-linked the PVBP groups on the polymer to yield particles that
      withstood extremes of temperature, ionic strength, and chemical etching.
      Streptavidin was attached to [PS-co-PVBP]-b-PAA-coated particles using the same
      noncovalent and covalent conjugation protocols used to bind biomolecules to
      divinylbenzene-cross-linked PS microspheres. We expect that these particles will
      be useful as plasmonic, highly light-scattering and light-absorbing analogs to
      fluorescently labeled PS nanospheres.

PMID- 17530873
TI  - Unidirectional crystallization of charged colloidal silica due to the diffusion
      of a base.
AB  - Dilute aqueous dispersions of charged colloidal silica (particle volume fraction
      = approximately 0.03-0.04, particle diameter = 110 nm) exhibit unidirectional
      crystal growth due to the diffusion of a weak base, pyridine (Py). Similar
      diffusion-crystallization is enabled by a salt of a weak acid and a strong base,
      sodium hydrogen carbonate (NaHCO3). The resulting crystals consist of columnar
      (or cubic) crystal grains with a maximum height of a few centimeters and a
      maximum width of 1 cm. The crystal growth process is attributed to a combination
      of (i) the diffusion of Py or NaHCO3 accompanied by a charging reaction of the
      silica particles and (ii) the charge-induced crystallization of the silica
      colloids. Theoretical growth curves based on the reaction-diffusion model for the
      case of Py were in good agreement with the observed curves. We also report the
      immobilization of the resulting large crystals by using a polymer hydrogel
      matrix.

PMID- 17530874
TI  - Nanoscale actuation of thermoreversible polymer brushes coupled with localized
      surface plasmon resonance of gold nanoparticles.
AB  - This paper describes the fabrication of hybrid nanoassemblies with polymer
      brushes and gold nanoparticles enabling detection of nanoscale optical changes
      based on localized surface plasmon resonance. The reversible and thermosensitive
      nanoscale actuation is achieved by combining stimuli-responsive polymer brushes
      and gold nanoparticles independently and selectively assembled on substrates.
      These hybrid nanoassemblies are assembled on numerous substrates and will be
      applicable for optoelectronics, nanoactuator, and nanosensor applications.

PMID- 17530875
TI  - Mitochondrial proteomic analysis and characterization of the intracellular
      mechanisms of bis(7)-tacrine in protecting against glutamate-induced
      excitotoxicity in primary cultured neurons.
AB  - Increasing evidence supports that the mitochondrial dysfunction, mainly caused by
      abnormal changes in mitochondrial proteins, plays a pivotal role in glutamate
      induced excitotoxicity, which is closely associated with the pathogenesis of
      acute and chronic neurodegenerative disorders, such as stroke and Alzheimer's
      disease. In this study, post-treatment of cerebellar granule neurons with bis(7)
      tacrine significantly reversed declines in mitochondrial membrane potential, ATP
      production, and neuronal cell death induced by glutamate. Moreover, this reversal
      was independent of NMDA antagonism, acetylcholinesterase inhibition, and
      cholinergic pathways. Using two-dimensional differential in-gel electrophoresis,
      we conducted a comparative analysis of mitochondrial protein patterns. In all, 29
      proteins exhibiting significant differences in their abundances were identified
      in the glutamate-treated group when compared with the control. The expression
      patterns in 22 out of these proteins could be reversed by post-treatment with
      bis(7)-tacrine. Most of the differentially expressed proteins are involved in
      energy metabolism, oxidative stress, and apoptosis. In particular, the altered
      patterns of four of these proteins were further validated by Western blot
      analysis. Our findings suggest that multiple signaling pathways initiated by the
      altered mitochondrial proteins may mediate glutamate-induced excitotoxicity and
      also offer potentially useful intracellular targets for the neuroprotection
      provided by bis(7)-tacrine.

PMID- 17530876
TI  - Optimization of mass spectrometry-compatible surfactants for shotgun proteomics.
AB  - An optimization and comparison of trypsin digestion strategies for
      peptide/protein identifications by microLC-MS/MS with or without MS compatible
      detergents in mixed organic-aqueous and aqueous systems was carried out in this
      study. We determine that adding MS-compatible detergents to proteolytic digestion
      protocols dramatically increases peptide and protein identifications in complex
      protein mixtures by shotgun proteomics. Protein solubilization and proteolytic
      efficiency are increased by including MS-compatible detergents in trypsin
      digestion buffers. A modified trypsin digestion protocol incorporating the MS
      compatible detergents consistently identifies over 300 proteins from 5 microg of
      pancreatic cell lysates and generates a greater number of peptide identifications
      than trypsin digestion with urea when using LC-MS/MS. Furthermore, over 700
      proteins were identified by merging protein identifications from trypsin
      digestion with three different MS-compatible detergents. We also observe that the
      use of mixed aqueous and organic solvent systems can influence protein
      identifications in combinations with different MS-compatible detergents. Peptide
      mixtures generated from different MS-compatible detergents and buffer
      combinations show a significant difference in hydrophobicity. Our results show
      that protein digestion schemes incorporating MS-compatible detergents generate
      quantitative as well as qualitative changes in observed peptide identifications,
      which lead to increased protein identifications overall and potentially increased
      identification of low-abundance proteins.

PMID- 17530877
TI  - Correlation between rheological properties of zinc carboxylate liquids and
      molecular structure.
AB  - Using Fourier transform infrared spectroscopy (FTIR), the viscosity of zinc 2
      ethylhexanoate liquid has been found to correlate with the intensity of an
      asymmetric COO stretching resonance at 1632 cm-1. This is consistent with the
      presence of the zinc carboxylate polymer, catena-2-ethylhexanato-(O,O')-tri-micro
      2-ethylhexanato-(O,O')-dizinc(II) as the origin of the viscosity, a conclusion
      that is further supported by theoretical predictions. Density functional theory
      has been used to assign the IR spectra of the zinc carboxylate dimer, catena-2
      ethylhexanato-(O,O')-di-(tri-micro-2-ethylhexanato-(O,O')-dizinc(II)-formic)
      acid, and the model of the molecular liquid, micro-4-oxo-hexakis-(micro-2
      ethylhexanato)-tetrazinc(II). The predicted spectra indicate that the decreased
      symmetry of the polymer relative to the zinc 2-ethylhexanoate liquid increases
      the intensity of the asymmetric carboxylate stretch at 1632 cm-1 and leads to the
      observed correlation.

PMID- 17530878
TI  - Dynamics of mobile ions: fitting of CKN frequency response data without an excess
      wing.
AB  - Ion dynamics effects and the resulting dispersed frequency response of conducting
      materials have often been explained in the past by a combination of the Moynihan
      original modulus formalism (OMF) and the Ngai coupling model (NCM). These
      incorrect approaches and their inappropriate conclusions are replaced by
      alternate, Kohlrausch-related physically reasonable conductive-system fitting and
      interpretation models that are then used for the analysis of both limited-range
      and wide-range data for the supercooled liquid 0.4Ca(NO3)2*0.6KNO3 (CKN).
      Detailed analysis of the limited-range 342 K data at the electric modulus
      immittance level shows that OMF fitting leads to an excess wing and that more
      appropriate models fit the data well without such a wing. Further, although such
      models allow estimation of the bulk dipolar dielectric constant of the material,
      as well as one associated only with mobile charges, they lead to implausibly
      small estimates of the important Kohlrausch K1 model shape parameter, beta1, and
      lead to an inadequate determination of its characteristic relaxation time.
      Therefore, wide-range CKN data sets extending to nearly 1012 Hz for the
      temperatures 342, 350, 356, and 361 K were very well-fitted with a more detailed
      composite model but one still involving K1 response. All model parameters were
      well-determined with no excess wings; beta1 estimates were all much closer to the
      universal value of 1/3; and the estimated model parameters led to a Boson peak
      beyond 1012 Hz, to very large thermal activation energies, and to evidence that
      the mobile charge concentration reached a saturation value at about 356 K. Such
      results do not support assumptions about variable ion-ion correlation, a mainstay
      of the OMF and NCM approaches. Finally, it is shown that although excess wings
      can sometimes be eliminated by using just an appropriate bulk fitting model and
      series blocking-electrode capacitor, as shown for the present narrow-range data,
      adequate fitting of the present wide-range data sets over their full spans of as
      much as 13 decades required the addition of an additional series dispersive
      response model to the composite model. This addition seems likely to be required
      to take adequate account of the presence of more than one species of mobile
      charge in CKN.

PMID- 17530879
TI  - Structure of SDS micelles with propylene carbonate as cosolvent: a PGSE-NMR and
      SAXS study.
AB  - The effect of propylene carbonate on SDS micelles was investigated by means of
      pulsed gradient spin-echo (PGSE) NMR, small-angle X-ray scattering (SAXS),
      conductivity and ion-selective electrode (ISE) measurements. The knowledge of the
      cosolvent partition between continuous phase and micelles (obtained by means of
      PGSE-NMR) allowed the identification of relevant dilution paths. Along these
      paths the system is composed of identical micelles that become more and more
      diluted. The extrapolation of measured self-diffusion coefficient to infinite
      dilution (where direct and hydrodynamic interactions are negligible) permits the
      determination of hydrodynamic size of the micelles. Moreover, the micelle
      ionization degree (measured by means of ISE) combined with PGSE-NMR and
      conductivity data furnishes an estimate of the aggregation number without any
      assumptions on micellar shape. On the other hand, troublesome hydrodynamic
      interactions are irrelevant to SAXS, and scattering data collected at fixed
      composition can be analyzed according to a reasonable model by exploiting the
      insight on the propylene carbonate partition gained through PGSE-NMR. By means of
      these approaches, we have found that propylene carbonate acts mainly as
      cosurfactant for the SDS micelles, decreasing their size and aggregation number
      by increasing the mean headgroup area of SDS.

PMID- 17530880
TI  - Effect of physical aging on nucleation of amorphous indomethacin.
AB  - Differential scanning calorimetry has been used to study glassy indomethacin aged
      at 0 and -10 degrees C for periods of time up to 109 and 210 days, respectively.
      The results demonstrate the emergence of a small melting peak of the alpha
      polymorph after aging for 69 days at 0 degrees C and for 147 days at -10 degrees
      C (i.e., approximately 55 degrees C below the glass-transition temperature) that
      provides evidence of nucleation occurring in the temperature region of the beta
      relaxation. The evolution of an endothermic recovery peak temperature features a
      plateau at longer annealing times that suggests that the glass has made
      significant progress toward reaching the supercooled liquid state. It has been
      found that the melting peaks become detectable after the recovery peak has
      reached the plateau. The results highlight the importance of studying physical
      aging in the temperature region of the beta-relaxation as a means of evaluating
      the physical stability of amorphous pharmaceutical materials.

PMID- 17530881
TI  - Opposing effects of cation binding and hydration on the bending rigidity of
      anionic lipid bilayers.
AB  - We correlate the molecularly realistic self-consistent field predictions for the
      mean bending modulus kc of charged lipid vesicles with experimental observations
      of the size R of corresponding vesicles that are produced by the freeze-thaw
      method. We elaborate on the Ansatz that the bending modulus is related to the
      membrane persistence length and that this length scale sets the radius of the
      vesicles. Alkali cations have a remarkable effect on the mean bending modulus and
      thus on the equilibrium radius of negatively charged entropically stabilized
      dioleoylphosphatidylglycerol (DOPG) vesicles. Where cation hydration typically
      results in thicker and thus stiffer membranes, specific adsorption to the bilayer
      surface results in a decrease of the surface charge density and the thickness of
      the membrane-associated electric double layer. As a result of these opposing
      effects on kc and R, the largest DOPG vesicles are found in the presence of K+,
      which combines an intermediate hydration enthalpy and PG-binding affinity.

PMID- 17530882
TI  - Ultrafast fluorescence resonance energy transfer in the micelle and the gel phase
      of a PEO-PPO-PEO triblock copolymer: excitation wavelength dependence.
AB  - Fluorescence resonance energy transfer (FRET) from coumarin 480 (C480) to
      rhodamine 6G (R6G) is studied in the micelle and the gel phase of a triblock
      copolymer, (PEO)20-(PPO)70-(PEO)20 (Pluronic P123 (P123)) by picosecond and
      femtosecond emission spectroscopy. The time constants of FRET were obtained from
      the rise time of the acceptor (R6G) emission. In a P123 micelle, FRET occurs in
      multiple time scales: 2.5, 100, and 1700 ps. In the gel phase, three rise
      components are observed: 3, 150, and 2600 ps. According to a simple Forster
      model, the ultrafast (2.5 and 3 ps) components of FRET correspond to donor
      acceptor distance RDA=13 +/- 2 A. The ultrafast FRET occurs between a donor and
      an acceptor residing at close contact at the corona (PEO) region of a P123
      micelle. With increase in the excitation wavelength (lambdaex) from 375 to 435
      nm, the relative contribution of the ultrafast component of FRET ( approximately
      3 ps) increases from 13% to 100% in P123 micelle and from 1% to 100% in P123 gel.
      It is suggested that at lambdaex = 435 nm, mainly the highly polar peripheral
      region is probed where FRET is very fast due to close proximity of the donor and
      the acceptor. The 100 and 150 ps components correspond to RDA = 25 +/- 2 A and
      are ascribed to FRET from C480 deep inside the micelle to an acceptor (R6G) in
      the peripheral region. The very long component of FRET (1700 ps in micelle and
      2600 ps component in gel) may arise from diffusion of the donor from outside the
      micelle to the interior followed by fast FRET.

PMID- 17530883
TI  - Structure-activity relationships of alphaS1-casomorphin using AM1 calculations
      and molecular dynamics simulations.
AB  - This paper investigates the structure-activity relationships of alphaS1
      casomorphin (alphaS1-CM) using AM1 calculations and molecular dynamics (MD)
      simulations. Previous studies have shown that this peptide has remarkable opioid
      actions, and not only has a high affinity toward all three subtypes (kappa1
      kappa3) of the kappa-opioid sites, but also inhibits the proliferation of the
      T47D human breast cancer cell line. The systematic conformer search performed by
      the AM1 calculations is based on the torsional angles of the Val2-Pro3 (omega2)
      and Phe4-Pro5 (omega4) amide bonds. The AM1 results reveal that the alphaS1-CM
      conformers strongly favor the cis/cis pair of the omega2/omega4 amide bonds in
      the minimized energy state. Furthermore, the picture of these stable conformers
      is found to be a strong interaction of the coulomb's force between two
      terminuses. MD simulations are performed to investigate the features of both the
      structural stability and pharmacological activity of alphaS1-CM in aqueous
      solution. The simulation results reveal that the omega2/omega4 amide bonds favor
      the cis/cis status in the stable state. Furthermore, the pharmacophoric distance
      between two aromatic rings is found to be 5.0 approximately 5.4A. The chi1
      rotamers of the Tyr and Phe residues show a preference for gauche (-) and trans,
      respectively. The side chain rotamers of alphaS1-CM are competed to those of
      other opioid ligands with a known potency and selectivity for delta- and mu
      opioid receptors. Finally, we address a likely kappa pharmacophore model compared
      to the delta pharmacophore model.

PMID- 17530884
TI  - Molecular dynamics simulations of rhodopsin in different one-component lipid
      bilayers.
AB  - Four 20 ns molecular dynamic simulations of rhodopsin embedded in different one
      component lipid bilayers have been carried out to ascertain the importance of
      membrane lipids on the protein structure. Specifically, dimyristoyl
      phosphatidylcholine (DMPC), dipalmitoyl phosphatidylcholine (DPPC), palmitoyl
      oleoyl phosphatidylcholine (POPC), and palmitoyl linoleyl phosphatidylcholine
      (PLPC) lipid bilayers have been considered for the present work. The results
      reported here provide information on the hydrophobic matching between the protein
      and the bilayer and about the differential effects of the protein on the
      thickness of the different membranes. Furthermore, a careful analysis of the
      individual protein-lipid interactions permits the identification of residues that
      exhibit permanent interactions with atoms of the lipid environment that may
      putatively act as hooks of the protein to the membrane. The analysis of the
      trajectories also provides information about the effect of the bilayer on the
      protein structure, including secondary structural elements, salt bridges, and
      rigid-body motions.

PMID- 17530885
TI  - Solvation and rotational dynamics of coumarin 153 in ionic liquids: comparisons
      to conventional solvents.
AB  - Steady-state and time-resolved emission spectroscopy with 25 ps resolution are
      used to measure equilibrium and dynamic aspects of the solvation of coumarin 153
      (C153) in a diverse collection of 21 room-temperature ionic liquids. The ionic
      liquids studied here include several phosphonium and imidazolium liquids
      previously reported as well as 12 new ionic liquids that incorporate two
      homologous series of ammonium and pyrrolidinium cations. Steady-state absorption
      and emission spectra are used to extract solvation free energies and
      reorganization energies associated with the S0 <--> S1 transition of C153. These
      quantities, especially the solvation free energy, vary relatively little in ionic
      liquids compared to conventional solvents. Some correlation is found between
      these quantities and the mean separation between ions (or molar volume). Time
      resolved anisotropies are used to observe solute rotation. Rotation times
      measured in ionic liquids correlate with solvent viscosity in much the same way
      that they do in conventional polar solvents. No special frictional coupling
      between the C153 and the ionic liquid solvents is indicated by these times. But,
      in contrast to what is observed in most low-viscosity conventional solvents,
      rotational correlation functions in ionic liquids are nonexponential. Time
      resolved Stokes shift measurements are used to characterize solvation dynamics.
      The solvation response functions in ionic liquids are also nonexponential and can
      be reasonably represented by stretched-exponential functions of time. The
      solvation times observed are correlated with the solvent viscosity, and the much
      slower solvation in ionic liquids compared to dipolar solvents can be attributed
      to their much larger viscosities. Solvation times of the majority of ionic
      liquids studied appear to follow a single correlation with solvent viscosity.
      Only liquids incorporating the largest phosphonium cation appear to follow a
      distinctly different correlation.

PMID- 17530886
TI  - Effect of substituents in aromatic amines on the activation energy of epoxy-amine
      reaction.
AB  - Differential scanning calorimetry has been used to study the kinetics of epoxy
      amine curing reaction between diglycidyl ether of 4,4'-bisphenol and aromatic
      amines with different electron-withdrawing/-donating substituents. The
      substituents include -NO2, -CN, -OCH3, -OH, and -CH3 groups. An advanced
      isoconversional method has been employed to determine the effective activation
      energy of the respective processes. An attempt has been made to link the
      experimental values with the results of quantum chemistry calculations. It has
      been found that regardless of the electron-withdrawing/-donating properties the
      presence of a substituent of a large negative charge in the ortho position causes
      an increase in the activation energy to approximately 100 kJ mol-1 from the
      normally observed values of 50-60 kJ mol-1.

PMID- 17530887
TI  - Crystallization of AlPO4-5 aluminophosphate molecular sieve prepared in fluoride
      medium: a multinuclear solid-state NMR study.
AB  - In the present work, multinuclear solid-state NMR techniques, combined with
      powder X-ray diffraction (PXRD) and infrared (IR) spectroscopy, are employed to
      monitor the crystallization of AlPO4-5 aluminophosphate prepared in the presence
      of HF under hydrothermal condition. The crystallization process is characterized
      by the evolution of intermediate gels, in which the long-rang ordering
      arrangement is probed by PXRD, revealing the threshold of the crystallization
      around 120 min. The appearance of 31P signals at ca. -22 and -29 ppm due to the
      structural P-O-Al unit and 19F signal at -120 ppm due to the structural F-Alpen-O
      P unit in the NMR spectra of the series gels indicates that the crystalline
      framework is starting to form. The onset of the crystallization is also evidenced
      by the presence of the pentacoordinated Al in the structural F-Alpen-O-P unit
      which is considered to be associated with the ordered framework. More information
      about the local ordering of the gels is obtained from two-dimensional 27Al -->
      31P heteronuclear correlation (HETCOR) and 31P/27Al double-resonance experiments.
      In combination with 1H --> 31P cross-polarization/magic-angle spinning (CP/MAS)
      experiments, two microdomains can be identified in the 120 min heated gel. A
      possible evolution mechanism of the gels consisting of three successive stages is
      proposed for the crystallization process.

PMID- 17530888
TI  - Adsorption of sodium alkyl sulfate homologues at the air/solution interface.
AB  - Experimental results are presented on the adsorption of sodium alkyl sulfate
      homologues (nC = 8-14) at the air/solution interface. The adsorption isotherms
      calculated from equilibrium surface-tension vs concentration data and the
      critical micelle concentration change regularly with the length of the alkyl
      chain; the odd/even effect was not observed. The isotherms were analyzed using a
      model-independent approach. The analysis indicates that the total driving force
      of adsorption reaches a plateau value and becomes constant in the function of the
      adsorbed amount in the case of each homologue. With the use of different
      electrostatic models, it was demonstrated that this behavior is consistent with a
      saturation-type hydrophobic driving-force contribution, which can be interpreted
      by the development of a liquidlike alkane environment in the adsorbed layer above
      a "critical" adsorbed amount.

PMID- 17530889
TI  - Structure and stability of complex coacervate core micelles with lysozyme.
AB  - Encapsulation of enzymes by polymers is a promising method to influence their
      activity and stability. Here, we explore the use of complex coacervate core
      micelles for encapsulation of enzymes. The core of the micelles consists of
      negatively charged blocks of the diblock copolymer PAA42PAAm417 and the
      positively charged homopolymer PDMAEMA150. For encapsulation, part of the
      positively charged homopolymer was replaced by the positively charged globular
      protein lysozyme. We have studied the formation, structure, and stability of the
      resulting micelles for three different mixing ratios of homopolymer and lysozyme:
      a system predominantly consisting of homopolymer, a system predominantly
      consisting of lysozyme, and a system where the molar ratio between the two
      positively charged molecules was almost one. We also studied complexes made of
      only lysozyme and PAA42PAAm417. Complex formation and the salt-induced
      disintegration of the complexes were studied using dynamic light-scattering
      titrations. Small-angle neutron scattering was used to investigate the structures
      of the cores. We found that micelles predominantly consisting of homopolymer are
      spherical but that complex coacervate core micelles predominantly consisting of
      lysozyme are nonspherical. The stability of the micelles containing a larger
      fraction of lysozyme is lower.

PMID- 17530890
TI  - Collagen fibril structure is affected by collagen concentration and decorin.
AB  - Collagen fibrils were obtained in vitro by aggregation from acid-soluble type I
      collagen at different initial concentrations and with the addition of decorin
      core or intact decorin. All specimens were observed by scanning electron
      microscopy and atomic force microscopy. In line with the findings of other
      authors, lacking decorin, collagen fibrils undergo an extensive lateral
      association leading to the formation of a continuous three-dimensional network.
      The addition of intact decorin or decorin core was equally effective in
      preventing lateral fusion and restoring the normal fibril appearance. In
      addition, the fibril diameter was clearly dependent on the initial collagen
      concentration but not on the presence/absence of proteoglycans. An unusual fibril
      structure was observed as a result of a very low initial collagen concentration,
      leading to the formation of huge, irregular superfibrils apparently formed by the
      lateral coalescence of lesser fibrils, and with a distinctive coil-structured
      surface. Spots of incomplete fibrillogenesis were occasionally found, where all
      fibrils appeared made of individual, interwined subfibrils, confirming the
      presence of a hierarchical association mechanism.

PMID- 17530891
TI  - Synthesis and in vitro hydroxyapatite binding of peptides conjugated to calcium
      binding moieties.
AB  - To confer bone-binding properties to proteins and other biological agents that
      lack specific targeting capacity, model peptide-based molecules were synthesized
      containing poly(aspartic acid), poly(glutamic acid), or a bisphosphonate
      (pamidronate). These motifs have well-documented affinities to hydroxyapatite, a
      property desirable for the targeting of molecules to bone for drug delivery and
      tissue engineering applications. Model peptides of increasing molecular mass (5
      33 amino acids) were directly conjugated to eight aspartic acids (Asp8), eight
      glutamic acids (Glu8), or pamidronate, purified by high-performance liquid
      chromatography, and characterized by matrix-assisted laser desorption ionization
      time-of-flight (MALDI-TOF) mass spectroscopy. The modified peptides were
      incubated with hydroxyapatite in phosphate-buffered saline at physiological
      conditions over 24 h. This study revealed a significant amount (>90%) of
      conjugated peptides adsorbed to the hydroxyapatite as compared to unmodified
      peptides (<5%). It was found that while there were significant differences
      between the different hydroxyapatite-binding and control groups for all time
      points, the size of the peptide had no statistical effect on peptide
      hydroxyapatite binding. These results demonstrate that bisphosphonate and
      oligopeptide conjugates hold great promise for the development of new bioactive
      molecules for bone-specific applications.

PMID- 17530892
TI  - Evidence for egg-box-compatible interactions in calcium-alginate gels from fiber
      X-ray diffraction.
AB  - The structures of guluronic-acid-rich alginate in the acid and calcium forms were
      investigated using fiber X-ray diffraction. Data recorded for alginate fibers in
      the acid form show a repeat along the chain axis of c = 0.87 nm, a value that is
      in agreement with the one measured by Atkins et al. (Biopolymers 1973, 12, 1865)
      and contradicts a repeat of 0.78 nm recently suggested by Li et al.
      (Biomacromolecules 2007, 8, 464). In the Ca2+ form, our observations indicate
      that the junction zone involves dimerization of polymer chains through Ca2+
      coordination according to the egg-box model. For reasons that are not understood
      at present, coordination of the divalent cations reduces the ability for the
      lateral crystallographic packing of the dimers. A proposed model for the junction
      zone involves polymer chains packed on a hexagonal lattice with a lattice
      constant a = 0.66 nm. Random pairs of chains form dimers through coordination of
      Ca2+ cations. Further lateral interaction between dimers is mediated by
      disordered Na+ and Ca2+ cations, water molecules, and hydrogen bonding.

PMID- 17530893
TI  - Fabrication and characterization of biodegradable poly(3-hydroxybutyrate)
      composite containing bioglass.
AB  - Bacterially derived poly(3-hydroxybutyrate) (P(3HB)) has been used to produce
      composite films by incorporating Bioglass particles (<5 microm) in 5 and 20 wt %
      concentrations. P(3HB) was produced using a large scale fermentation technique.
      The polymer was extracted using the Soxhlet technique and was found to have
      similar thermal and structural properties to the commercially available P(3HB).
      The effects of adding Bioglass on the microstructure surface and thermal and
      mechanical properties were examined using differential scanning calorimetry,
      dynamic mechanical analysis (DMA), X-ray diffraction, surface interferometry,
      electron microscopy, and nanoindentation. The addition of increasing
      concentrations of Bioglass in the polymer matrix reduced the degree of
      crystallinity of the polymer as well as caused an increase in the glass
      transition temperature as determined by DMA. The presence of Bioglass
      particulates reduced the Young's modulus of the composite. The storage modulus
      and the loss modulus, however, increased with the addition of 20 wt % Bioglass. A
      short period (28 days) in vitro bioactivity study in simulated body fluid
      confirmed the bioactivity of the composites, demonstrated by the formation of
      hydroxyapatite crystals on the composites' surface.

PMID- 17530894
TI  - Bifunctional building blocks for glyco-architectures by TiCl4 -promoted ring
      opening of cyclodextrin derivatives.
AB  - During our studies on the preparation of blocklike substituted 1,4-glucans by
      cationic ring-opening polymerization,1,2 we found that TiCl4 behaves differently
      from common initiators like Et3O+X- (X = PF6, SbCl6), BF3.Et2O, or methyl
      triflate, causing only ring opening under formation of alpha-maltooligosyl
      chlorides bearing one free hydroxyl group (4-OH) at the nonreducing end. These
      compounds are valuable building blocks for the preparation of new glyco
      architectures since they are easily accessible starting materials for direct
      glycosylations or the preparation of a variety of oligomeric glycosyl donors like
      alkyl glycosides, thioglycosides, or azides. We successfully carried out and
      optimized the TiCl4-promoted ring opening with per-O-methylated, per-O-ethylated,
      and temporarily protected per-O-allylated cyclodextrins of various ring size. 1H
      NMR spectroscopy and high-pressure liquid chromatography-evaporative light
      scattering detection (HPLC-ELSD) were used to characterize the products.

PMID- 17530895
TI  - Synthesis of meso-extended tetraarylporphyrins.
AB  - The synthesis of five new meso-tetraarylporphyrins having pyridine, pyrimidine,
      or nitrile groups extending tetragonally via alkynyl linkages from the para
      positions is described. The radial extension is nearly double that of common
      porphyrins such as tetra-p-pyridylporphyrin. Practical quantities can be produced
      by Pd-coupling protocols when traditional methods fail. Applications of these
      extended porphyrins in the area of porous metal-organic frameworks are
      anticipated.

PMID- 17530896
TI  - Triazabicyclodecene: an effective isotope exchange catalyst in CDCl(3).
AB  - We describe the first effective H/D exchange reaction with acidic substrates in
      CDCl(3) at room temperature. The particularly mild reaction conditions involved
      (solvent, base, and temperature) allow the chemoselective deuteration of ketones
      over esters. An NMR study was conducted with the aim of rationalizing the results
      obtained in the presence of TBD as catalyst.

PMID- 17530897
TI  - Enantioselective fluorescent recognition of chiral acids by cyclohexane-1,2
      diamine-based bisbinaphthyl molecules.
AB  - The cyclohexane-1,2-diamine-based bisbinaphthyl macrocycles (S)-/(R)-5 and their
      cyclic and acyclic analogues are synthesized. The interactions of these compounds
      with various chiral acids are studied. Compounds (S)-/(R)-5 exhibit highly
      enantioselective fluorescent responses and high fluorescent sensitivity toward
      alpha-hydroxycarboxylic acids and N-protected amino acids. Among these
      interactions, (S)-mandelic acid (10(-3) M) led to over 20-fold fluorescence
      enhancement of (S)-5 (1.0 x 10(-5) M in benzene/0.05% DME) at the monomer
      emission, and (S)-hexahydromandelic acid (10(-3) M) led to over 80-fold
      fluorescence enhancement. These results demonstrate that (S)-5 is useful as an
      enantioselective fluorescent sensor for the recognition of the chiral acids. On
      the basis of the study of the structures of (S)-5 and the previously reported 1,2
      diphenylethylenediamine-based bisbinaphthyl macrocycle (S)-4, the large
      fluorescence enhancement of (S)-5 with a chirality-matched alpha
      hydroxycarboxylic acid is attributed to the formation of a structurally
      rigidified host-guest complex and the further interaction of this complex with
      the acid to suppress the photoinduced electron-transfer fluorescent quenching
      caused by the nitrogens in (S)-5.

PMID- 17530898
TI  - Efficient syntheses of C(8)-aryl adducts of adenine and guanine formed by
      reaction of radical cation metabolites of carcinogenic polycyclic aromatic
      hydrocarbons with DNA.
AB  - The synthesis of the C(8)-aryl adducts of adenine and guanine formed by reaction
      of the radical cation metabolites of carcinogenic polycyclic aromatic
      hydrocarbons (PAHs), such as benzo[a]pyrene (BP) and dibenzo[def,p]chrysene
      (DBC), with DNA is reported. The synthetic approach involves in the key step
      direct reaction of a PAH aldehyde with a di- or triamine precursor of a purine.
      The method is operationally simple, affords good yields of adducts, and is broad
      in its scope. The C(8)-aryl adducts of adenine and guanine derived from BP (6-BP
      8-Ade and 6-BP-8-Gua) and DBC (10-DBC-8-Ade and 10-DBC-8-Gua) were synthesized in
      good yields by this method. Analogous C(8)-aryl adenine and guanine derivatives
      of other PAHs (anthracene, benz[a]anthracene, and chrysene) were also readily
      prepared via this approach. This method of synthesis is superior to the only
      method that is currently available. It entails direct reaction of short-lived PAH
      radical cations (generated electrochemically or chemically) with 2'
      deoxyribonucleosides or the corresponding purine bases. It provides the adducts
      in low yields accompanied by complex mixtures of secondary products. An
      alternative synthesis that involves Pd-catalyzed Suzuki-Miyaura coupling of
      arylboronic acids with 8-bromopurine nucleosides was also investigated. Although
      the C(8)-purine adducts of PAHs, such as naphthalene, phenanthrene, pyrene, and
      chrysene, could be prepared by this method, analogous adducts of carcinogenic
      PAHs and other structurally related PAHs, e.g., anthracene, benz[a]anthracene,
      benzo[a]pyrene, and dibenzo[def,p]chrysene, could not be obtained. This
      difference was shown to be a consequence of the facility of competing hydrolytic
      deboronation of the corresponding arylboronic acids.

PMID- 17530899
TI  - Synthesis of chinensines A-E.
AB  - Short and efficient syntheses of coronarin E (4) and chinensines A-E (5-9) have
      been accomplished. The use of two different types of reaction of singlet oxygen
      ((1)O(2)) lies at the heart of the synthetic strategy. The syntheses have
      facilitated the clarification of certain previously unknown, or unconfirmed,
      stereochemical details (the relativity stereochemistries of chinensines D and E
      and the absolute stereochemistries for all the synthesized family members).

PMID- 17530900
TI  - Palladium-catalyzed potassium enoxyborate alkylation of enantiopure Hajos-Parrish
      indenone to construct rearranged steroid ring systems.
AB  - Here we report the stereo- and regiospecific C-6 alkylation of a trans-inden-5
      one (from optically pure Hajos-Parrish ketone) with allylic electrophiles. Use of
      this alkylation procedure has led to an improved synthesis of the benz[f]indene
      ring system and the first enantiospecific total syntheses of the
      cyclopenta[b]anthracene and cyclopenta[b]phenanthrene ring systems (two synthetic
      routes).

PMID- 17530901
TI  - Assembly of conjugated enynes and substituted indoles via CuI/amino acid
      catalyzed coupling of 1-alkynes with vinyl iodides and 2
      bromotrifluoroacetanilides.
AB  - Cross-coupling of 1-alkynes with vinyl iodides occurs at 80 degrees C in dioxane
      catalyzed by CuI/N,N-dimethylglycine to afford conjugated enynes in good to
      excellent yields. Heating a mixture of 2-bromotrifluoroacetanilide, 1-alkyne, 2
      mol % of CuI, 6 mol % of L-proline, and K(2)CO(3) in DMF at 80 degrees C leads to
      the formation of the corresponding indole. This conversion involves a CuI/L
      proline-catalyzed coupling between aryl bromide and the 1-alkyne followed by a
      CuI-mediated cyclization process. An ortho-substituent effect directed by NHCOCF3
      enables the reaction to proceed under these mild conditions. Both aryl acetylenes
      and O-protected propargyl alcohol can be applied, leading to 5-, 6-, or 7
      substituted 2-aryl and protected 2-hydroxymethyl indoles in good yields. With
      simple aliphatic alkynes, however, lower yields were observed.

PMID- 17530902
TI  - Asymmetric synthesis of mono- and dinuclear bis(dipyrrinato) complexes.
AB  - The diastereoselective syntheses of Zn(II) bis(dipyrrinato) helicates is
      reported, involving ligands templated by the incorporation of homochiral binol
      within the linker joining the two dipyrrinato units. The most diastereoselective
      formation of dinuclear bis(dipyrrinato) helicates to date is reported. The
      formation of either mononuclear or dinuclear helicates can be tuned by varying
      the length of the linker between the dipyrrinato units and by varying the
      complexation procedure. The neutral dipyrrinato helicates were readily analyzed
      by HPLC to ascertain diastereoselectivity, and circular dichroism studies
      revealed the helical nature of the complexes. The molar ellipticities of the
      helicates produced by diastereoselective complexation are very large in the
      visible region and typically correspond to binol moieties in the UV region.
      Extensive X-ray crystallographic investigations further confirmed the helicity of
      the mononuclear Zn(II) helicates and identified significant interlayer
      displacement and bending within crystals.

PMID- 17530903
TI  - Palladium-catalyzed cyclization of 1,omega-dienols: multiple ways to
      intramolecularly trap a carbocation.
AB  - The tandem catalytic cyclization-rearrangement of 1,omega-dien-3-ols by
      palladium(II) produces different types of products, depending on the structure of
      starting material. The pinacol rearrangement, benzannulation, and oxy-Cope
      rearrangement are major pathways of transforming the putative sigma
      alkylpalladium carbocation. Turnover of the cyclization is achieved by beta
      hydride elimination and reoxidation of palladium with benzoquinone. The overall
      course of the reaction is very sensitive to small changes in the substrate
      structure.

PMID- 17530904
TI  - Design and synthesis of a cell-permeable synthetic transcription factor mimic.
AB  - Synthetic molecules capable of activating the expression of specific genes are of
      great interest as tools for biological research and, potentially, as a novel
      class of pharmaceutical agents. It has been demonstrated previously that such
      synthetic transcription factor mimics (STFMs) can be constructed by connecting a
      sequence-specific DNA-binding module to a molecule capable of binding to the
      transcriptional machinery via a suitable linker. These chimeras mimic the two
      basic properties of native transcription factors, which are able to recognize a
      promoter sequence specifically and to recruit the transcriptional machinery to
      that promoter. However, none of the compounds of this type reported to date have
      been shown to function in living cells. We report here the first example of a
      cell-permeable STFM that activates the transcription of a reporter gene in
      mammalian cells. The compound is composed of a cell-permeable coactivator-binding
      peptoid fused to a DNA-binding hairpin polyamide. The peptoid was identified by
      screening a combinatorial library of approximately 50,000 compounds for binding
      to the KIX domain of the CREB-binding protein (CBP), a mammalian transcription
      coactivator. When incubated with cultured HeLa cells carrying a luciferase
      reporter plasmid bearing several hairpin polyamide-binding sites, a 5-fold
      increase in luciferase expression was observed. These experiments set the stage
      for the identification of hairpin polyamide-peptoid conjugates that are targeted
      to native genes.

PMID- 17530905
TI  - Human pharmaceuticals in the aquatic environment: a challenge to Green Chemistry.

PMID- 17530906
TI  - "Green" atom transfer radical polymerization: from process design to preparation
      of well-defined environmentally friendly polymeric materials.

PMID- 17530907
TI  - Designing small molecules for biodegradability.

PMID- 17530909
TI  - Photocatalysis for the formation of the C-C bond.

PMID- 17530908
TI  - A green chemistry approach to asymmetric catalysis: solvent-free and highly
      concentrated reactions.

PMID- 17530910
TI  - Getting to the core of the problem: origin of the luminescence from (Mg,Zn)O
      heterostructured nanowires.
AB  - We have measured the time-resolved, X-ray excited optical luminescence spectra
      from two types of MgxZn(1-x)O core-shell, heterostructured nanowires: type I,
      with a small x, wurtzite core, encased in a larger x, wurtzite sheath; and type
      II, with a wurtzite core (x approximately 0), encased in a rock-salt sheath
      (x>0.62). By monitoring the X-ray energy dependence of the various luminescence
      peaks, we have determined the local environment of the sites where these peaks
      originate.

PMID- 17530911
TI  - Ultra-low contact resistance of epitaxially interfaced bridged silicon nanowires.
AB  - Laterally oriented single-crystal silicon nanowires are epitaxially grown between
      highly doped vertically oriented silicon electrodes in the form of nanobridges.
      Resistance values extracted from the current-voltage measurements for a large
      number of nanobridges with varying lengths and diameters are used to propose a
      model which highlights the relative contribution of the contact resistance to the
      total resistance for nanowire-based devices. It is shown that the contact
      resistance depends on the effective conducting cross-section area and hence is
      influenced by the presence of a surface depletion layer. On the basis of our
      measured data and constructed model, we estimated the specific contact resistance
      to be in the range 3.74 x 10(-6) to 5.02 x 10(-6) Omega cm2 for our epitaxial
      interfacing method. This value is at least an order of magnitude lower than that
      of any known contact made to nanowires with an evaporated metal film, a common
      method for integrating semiconductor nanowires in devices and circuits.

PMID- 17530912
TI  - Vertically oriented germanium nanowires grown from gold colloids on silicon
      substrates and subsequent gold removal.
AB  - A linker-free method to deposit citrate-stabilized Au colloids onto hydrogen
      terminated Si by acidifying the Au colloid solution with HF or HCl is presented.
      This method prevents oxide formation and provides a model system for studying
      orientation control of nanowires by epitaxy. Conditions are reported that result
      in vertically oriented Ge nanowires of uniform diameter and length on Si(111). We
      then present a method to remove Au catalysts from the nanowires with aqueous
      triiodide and HCl.

PMID- 17530913
TI  - Multiple exciton generation in films of electronically coupled PbSe quantum dots.
AB  - We study multiple exciton generation (MEG) in electronically coupled films of
      PbSe quantum dots (QDs) employing ultrafast time-resolved transient absorption
      spectroscopy. We demonstrate that the MEG efficiency in PbSe does not decrease
      when the QDs are treated with hydrazine, which has been shown to greatly enhance
      carrier transport in PbSe QD films by decreasing the interdot distance. The
      quantum yield is measured and compared to previously reported values for
      electronically isolated QDs suspended in organic solvents at approximately 4 and
      4.5 times the effective band gap. A slightly modified analysis is applied to
      extract the MEG efficiency and the absorption cross section of each sample at the
      pump wavelength. We compare the absorption cross sections of our samples to that
      of bulk PbSe. We find that both the biexciton lifetime and the absorption cross
      section increase in films relative to isolated QDs in solution.

PMID- 17530914
TI  - "Simple rules for editors"? Here is one rule to tackle neglected problems of
      publishing.

PMID- 17530916
TI  - Prediction of functional sites based on the fuzzy oil drop model.
AB  - A description of many biological processes requires knowledge of the 3-D
      structure of proteins and, in particular, the defined active site responsible for
      biological function. Many proteins, the genes of which have been identified as
      the result of human genome sequencing, and which were synthesized experimentally,
      await identification of their biological activity. Currently used methods do not
      always yield satisfactory results, and new algorithms need to be developed to
      recognize the localization of active sites in proteins. This paper describes a
      computational model that can be used to identify potential areas that are able to
      interact with other molecules (ligands, substrates, inhibitors, etc.). The model
      for active site recognition is based on the analysis of hydrophobicity
      distribution in protein molecules. It is shown, based on the analyses of proteins
      with known biological activity and of proteins of unknown function, that the
      region of significantly irregular hydrophobicity distribution in proteins appears
      to be function related.

PMID- 17530917
TI  - The emergence of alternative 3' and 5' splice site exons from constitutive exons.
AB  - Alternative 3' and 5' splice site (ss) events constitute a significant part of
      all alternative splicing events. These events were also found to be related to
      several aberrant splicing diseases. However, only few of the characteristics that
      distinguish these events from alternative cassette exons are known currently. In
      this study, we compared the characteristics of constitutive exons, alternative
      cassette exons, and alternative 3'ss and 5'ss exons. The results revealed that
      alternative 3'ss and 5'ss exons are an intermediate state between constitutive
      and alternative cassette exons, where the constitutive side resembles
      constitutive exons, and the alternative side resembles alternative cassette
      exons. The results also show that alternative 3'ss and 5'ss exons exhibit low
      levels of symmetry (frame-preserving), similar to constitutive exons, whereas the
      sequence between the two alternative splice sites shows high symmetry levels,
      similar to alternative cassette exons. In addition, flanking intronic
      conservation analysis revealed that exons whose alternative splice sites are at
      least nine nucleotides apart show a high conservation level, indicating intronic
      participation in the regulation of their splicing, whereas exons whose
      alternative splice sites are fewer than nine nucleotides apart show a low
      conservation level. Further examination of these exons, spanning seven vertebrate
      species, suggests an evolutionary model in which the alternative state is a
      derivative of an ancestral constitutive exon, where a mutation inside the exon or
      along the flanking intron resulted in the creation of a new splice site that
      competes with the original one, leading to alternative splice site selection.
      This model was validated experimentally on four exons, showing that they indeed
      originated from constitutive exons that acquired a new competing splice site
      during evolution.

PMID- 17530919
TI  - Bang-bang control of feeding: role of hypothalamic and satiety signals.
AB  - Rats, people, and many other omnivores eat in meals rather than continuously. We
      show by experimental test that eating in meals is regulated by a simple bang-bang
      control system, an idea foreshadowed by Le Magnen and many others, shown by us to
      account for a wide range of behavioral data, but never explicitly tested or tied
      to neurophysiological facts. The hypothesis is simply that the tendency to eat
      rises with time at a rate determined by satiety signals. When these signals fall
      below a set point, eating begins, in on-off fashion. The delayed sequelae of
      eating increment the satiety signals, which eventually turn eating off. Thus,
      under free conditions, the organism eats in bouts separated by noneating
      activities. We report an experiment with rats to test novel predictions about
      meal patterns that are not explained by existing homeostatic approaches. Access
      to food was systematically but unpredictably interrupted just as the animal tried
      to start a new meal. A simple bang-bang model fits the resulting meal-pattern
      data well, and its elements can be identified with neurophysiological processes.
      Hypothalamic inputs can provide the set point for longer-term regulation carried
      out by a comparator in the hindbrain. Delayed gustatory and gastrointestinal
      aftereffects of eating act via the nucleus of the solitary tract and other
      hindbrain regions as neural feedback governing short-term regulation. In this
      way, the model forges real links between a functioning feedback mechanism, neuro
      hormonal data, and both short-term (meals) and long-term (eating-rate regulation)
      behavioral data.

PMID- 17530920
TI  - Frequent gain and loss of functional transcription factor binding sites.
AB  - Cis-regulatory sequences are not always conserved across species. Divergence
      within cis-regulatory sequences may result from the evolution of species-specific
      patterns of gene expression or the flexible nature of the cis-regulatory code.
      The identification of functional divergence in cis-regulatory sequences is
      therefore important for both understanding the role of gene regulation in
      evolution and annotating regulatory elements. We have developed an evolutionary
      model to detect the loss of constraint on individual transcription factor binding
      sites (TFBSs). We find that a significant fraction of functionally constrained
      binding sites have been lost in a lineage-specific manner among three closely
      related yeast species. Binding site loss has previously been explained by
      turnover, where the concurrent gain and loss of a binding site maintains gene
      regulation. We estimate that nearly half of all loss events cannot be explained
      by binding site turnover. Recreating the mutations that led to binding site loss
      confirms that these sequence changes affect gene expression in some cases. We
      also estimate that there is a high rate of binding site gain, as more than half
      of experimentally identified S. cerevisiae binding sites are not conserved across
      species. The frequent gain and loss of TFBSs implies that cis-regulatory
      sequences are labile and, in the absence of turnover, may contribute to species
      specific patterns of gene expression.

PMID- 17530921
TI  - Ten simple rules for a good poster presentation.

PMID- 17530922
TI  - Nanobacteria: facts or fancies?

PMID- 17530923
TI  - Accumulation of pathological prion protein PrPSc in the skin of animals with
      experimental and natural scrapie.
AB  - Prion infectivity and its molecular marker, the pathological prion protein
      PrP(Sc), accumulate in the central nervous system and often also in lymphoid
      tissue of animals or humans affected by transmissible spongiform
      encephalopathies. Recently, PrP(Sc) was found in tissues previously considered
      not to be invaded by prions (e.g., skeletal muscles). Here, we address the
      question of whether prions target the skin and show widespread PrP(Sc) deposition
      in this organ in hamsters perorally or parenterally challenged with scrapie. In
      hamsters fed with scrapie, PrP(Sc) was detected before the onset of symptoms, but
      the bulk of skin-associated PrP(Sc) accumulated in the clinical phase. PrP(Sc)
      was localized in nerve fibres within the skin but not in keratinocytes, and the
      deposition of PrP(Sc) in skin showed no dependence from the route of infection
      and lymphotropic dissemination. The data indicated a neurally mediated
      centrifugal spread of prions to the skin. Furthermore, in a follow-up study, we
      examined sheep naturally infected with scrapie and detected PrP(Sc) by Western
      blotting in skin samples from two out of five animals. Our findings point to the
      skin as a potential reservoir of prions, which should be further investigated in
      relation to disease transmission.

PMID- 17530924
TI  - Centrosomal latency of incoming foamy viruses in resting cells.
AB  - Completion of early stages of retrovirus infection depends on the cell cycle.
      While gammaretroviruses require mitosis for proviral integration, lentiviruses
      are able to replicate in post-mitotic non-dividing cells. Resting cells such as
      naive resting T lymphocytes from peripheral blood cannot be productively infected
      by retroviruses, including lentiviruses, but the molecular basis of this
      restriction remains poorly understood. We demonstrate that in G0 resting cells
      (primary fibroblasts or peripheral T cells), incoming foamy retroviruses
      accumulate in close proximity to the centrosome, where they lie as structured and
      assembled capsids for several weeks. Under these settings, virus uncoating is
      impaired, but upon cell stimulation, Gag proteolysis and capsid disassembly
      occur, which allows viral infection to proceed. The data imply that foamy virus
      uncoating is the rate-limiting step for productive infection of primary G0 cells.
      Incoming foamy retroviruses can stably persist at the centrosome, awaiting cell
      stimulation to initiate capsid cleavage, nuclear import, and viral gene
      expression.

PMID- 17530925
TI  - p53 activation by knockdown technologies.
AB  - Morpholino phosphorodiamidate antisense oligonucleotides (MOs) and short
      interfering RNAs (siRNAs) are commonly used platforms to study gene function by
      sequence-specific knockdown. Both technologies, however, can elicit undesirable
      off-target effects. We have used several model genes to study these effects in
      detail in the zebrafish, Danio rerio. Using the zebrafish embryo as a template,
      correct and mistargeting effects are readily discernible through direct
      comparison of MO-injected animals with well-studied mutants. We show here
      indistinguishable off-targeting effects for both maternal and zygotic mRNAs and
      for both translational and splice-site targeting MOs. The major off-targeting
      effect is mediated through p53 activation, as detected through the transferase
      mediated dUTP nick end labeling assay, acridine orange, and p21 transcriptional
      activation assays. Concurrent knockdown of p53 specifically ameliorates the cell
      death induced by MO off-targeting. Importantly, reversal of p53-dependent cell
      death by p53 knockdown does not affect specific loss of gene function, such as
      the cell death caused by loss of function of chordin. Interestingly, quantitative
      reverse-transcriptase PCR, microarrays and whole-mount in situ hybridization
      assays show that MO off-targeting effects are accompanied by diagnostic
      transcription of an N-terminal truncated p53 isoform that uses a recently
      recognized internal p53 promoter. We show here that MO off-targeting results in
      induction of a p53-dependent cell death pathway. p53 activation has also recently
      been shown to be an unspecified off-target effect of siRNAs. Both commonly used
      knockdown technologies can thus induce secondary but sequence-specific p53
      activation. p53 inhibition could potentially be applicable to other systems to
      suppress off-target effects caused by other knockdown technologies.

PMID- 17530926
TI  - A mutation in the myostatin gene increases muscle mass and enhances racing
      performance in heterozygote dogs.
AB  - Double muscling is a trait previously described in several mammalian species
      including cattle and sheep and is caused by mutations in the myostatin (MSTN)
      gene (previously referred to as GDF8). Here we describe a new mutation in MSTN
      found in the whippet dog breed that results in a double-muscled phenotype known
      as the "bully" whippet. Individuals with this phenotype carry two copies of a two
      base-pair deletion in the third exon of MSTN leading to a premature stop codon at
      amino acid 313. Individuals carrying only one copy of the mutation are, on
      average, more muscular than wild-type individuals (p = 7.43 x 10(-6); Kruskal
      Wallis Test) and are significantly faster than individuals carrying the wild-type
      genotype in competitive racing events (Kendall's nonparametric measure, tau =
      0.3619; p approximately 0.00028). These results highlight the utility of
      performance-enhancing polymorphisms, marking the first time a mutation in MSTN
      has been quantitatively linked to increased athletic performance.

PMID- 17530927
TI  - NFIA haploinsufficiency is associated with a CNS malformation syndrome and
      urinary tract defects.
AB  - Complex central nervous system (CNS) malformations frequently coexist with other
      developmental abnormalities, but whether the associated defects share a common
      genetic basis is often unclear. We describe five individuals who share
      phenotypically related CNS malformations and in some cases urinary tract defects,
      and also haploinsufficiency for the NFIA transcription factor gene due to
      chromosomal translocation or deletion. Two individuals have balanced
      translocations that disrupt NFIA. A third individual and two half-siblings in an
      unrelated family have interstitial microdeletions that include NFIA. All five
      individuals exhibit similar CNS malformations consisting of a thin, hypoplastic,
      or absent corpus callosum, and hydrocephalus or ventriculomegaly. The majority of
      these individuals also exhibit Chiari type I malformation, tethered spinal cord,
      and urinary tract defects that include vesicoureteral reflux. Other genes are
      also broken or deleted in all five individuals, and may contribute to the
      phenotype. However, the only common genetic defect is NFIA haploinsufficiency. In
      addition, previous analyses of Nfia(-/-) knockout mice indicate that Nfia
      deficiency also results in hydrocephalus and agenesis of the corpus callosum.
      Further investigation of the mouse Nfia(+/-) and Nfia(-/-) phenotypes now reveals
      that, at reduced penetrance, Nfia is also required in a dosage-sensitive manner
      for ureteral and renal development. Nfia is expressed in the developing ureter
      and metanephric mesenchyme, and Nfia(+/-) and Nfia(-/-) mice exhibit
      abnormalities of the ureteropelvic and ureterovesical junctions, as well as bifid
      and megaureter. Collectively, the mouse Nfia mutant phenotype and the common
      features among these five human cases indicate that NFIA haploinsufficiency
      contributes to a novel human CNS malformation syndrome that can also include
      ureteral and renal defects.

PMID- 17530928
TI  - Zip4/Spo22 is required for class I CO formation but not for synapsis completion
      in Arabidopsis thaliana.
AB  - In budding yeast meiosis, the formation of class I interference-sensitive
      crossovers requires the ZMM proteins. These ZMM proteins are essential in forming
      a mature synaptonemal complex, and a subset of these (Zip2, Zip3, and Zip4) has
      been proposed to compose the core of synapsis initiation complexes (SICs).
      Zip4/Spo22 functions with Zip2 to promote polymerization of Zip1 along
      chromosomes, making it a crucial SIC component. In higher eukaryotes, synapsis
      and recombination have often been correlated, but it is totally unknown how these
      two processes are linked. In this study, we present the characterization of a
      higher eukaryote SIC component homologue: Arabidopsis AtZIP4. We show that
      mutations in AtZIP4 belong to the same epistasis group as Atmsh4 and eliminate
      approximately 85% of crossovers (COs). Furthermore, genetic analyses on two
      adjacent intervals of Chromosome I established that the remaining COs in Atzip4
      do not show interference. Lastly, immunolocalization studies showed that
      polymerization of the central element of the synaptonemal complex is not affected
      in Atzip4 background, even if it may proceed from fewer sites compared to wild
      type. These results reveal that Zip4 function in class I CO formation is
      conserved from budding yeast to Arabidopsis. On the other hand, and contrary to
      the situation in yeast, mutation in AtZIP4 does not prevent synapsis, showing
      that both aspects of the Zip4 function (i.e., class I CO maturation and synapsis)
      can be uncoupled.

PMID- 17530930
TI  - Discovery and analysis of evolutionarily conserved intronic splicing regulatory
      elements.
AB  - Knowledge of the functional cis-regulatory elements that regulate constitutive
      and alternative pre-mRNA splicing is fundamental for biology and medicine. Here
      we undertook a genome-wide comparative genomics approach using available
      mammalian genomes to identify conserved intronic splicing regulatory elements
      (ISREs). Our approach yielded 314 ISREs, and insertions of ~70 ISREs between
      competing splice sites demonstrated that 84% of ISREs altered 5' and 94% altered
      3' splice site choice in human cells. Consistent with our experiments,
      comparisons of ISREs to known splicing regulatory elements revealed that 40%-45%
      of ISREs might have dual roles as exonic splicing silencers. Supporting a role
      for ISREs in alternative splicing, we found that 30%-50% of ISREs were enriched
      near alternatively spliced (AS) exons, and included almost all known binding
      sites of tissue-specific alternative splicing factors. Further, we observed that
      genes harboring ISRE-proximal exons have biases for tissue expression and
      molecular functions that are ISRE-specific. Finally, we discovered that for
      Nova1, neuronal PTB, hnRNP C, and FOX1, the most frequently occurring ISRE
      proximal to an alternative conserved exon in the splicing factor strongly
      resembled its own known RNA binding site, suggesting a novel application of ISRE
      density and the propensity for splicing factors to auto-regulate to associate RNA
      binding sites to splicing factors. Our results demonstrate that ISREs are crucial
      building blocks in understanding general and tissue-specific AS regulation and
      the biological pathways and functions regulated by these AS events.

PMID- 17530929
TI  - Recent developments in yeast aging.
AB  - In the last decade, research into the molecular determinants of aging has
      progressed rapidly and much of this progress can be attributed to studies in
      invertebrate eukaryotic model organisms. Of these, single-celled yeast is the
      least complicated and most amenable to genetic and molecular manipulations.
      Supporting the use of this organism for aging research, increasing evidence has
      accumulated that a subset of pathways influencing longevity in yeast are
      conserved in other eukaryotes, including mammals. Here we briefly outline aging
      in yeast and describe recent findings that continue to keep this "simple"
      eukaryote at the forefront of aging research.

PMID- 17530931
TI  - Effects of high intensity / low volume and low intensity / high volume isokinetic
      resistance exercise on postexercise glucose tolerance.
AB  - The purpose of this study was to determine the effects of high intensity/ low
      volume (HILV) and low intensity/high volume (LIHV) isokinetic resistance exercise
      on postexercise glucose tolerance. Subjects (n = 10) participated in a
      counterbalanced, randomized design of 2 separate isokinetic resistance exercise
      trials (HILV and LIHV) of reciprocal concentric knee flexion and knee extension
      in a fasted state. Each bout was followed by a 45-minute oral glucose tolerance
      test (OGTT; 1.8 g.kg fat free mass(-1)). Blood samples were obtained every 15
      minutes to determine glucose and insulin concentrations. There was no difference
      in total work between the 2 trials (p = 0.229). Blood glucose was significantly
      higher at all time points compared with time 0 following the LIHV trial (p <
      0.05). Following the HILV trial, blood glucose was significantly elevated at 15
      and 30 minutes (p < 0.05), but returned to resting values by 45 minutes. Insulin
      concentration was significantly elevated following both trials at all time points
      (p < 0.05). Blood glucose and insulin were significantly higher following the
      LIHV at 30 and 45 minutes compared with the HILV trial (p < 0.05). These results
      demonstrate that although the total work output was similar across trials, high
      intensity muscle contraction is associated with an enhanced normalization of
      glucose homeostasis following a large postexercise oral glucose feed.

PMID- 17530932
TI  - Effects of taper on swimming force and swimmer performance after an experimental
      ten-week training program.
AB  - The purpose of this research was to examine how an 11-day taper after an 8.5-week
      experimental training cycle affected lactate levels during maximal exercise, mean
      force, and performance in training swimmers, independent of shaving,
      psychological changes, and postcompetition effects. Fourteen competition swimmers
      with shaved legs and torsos were recruited from the Sao Paulo Aquatic Federation.
      The training cycle consisted of a basic training period (endurance and quality
      phases) of 8.5 weeks, with 5,800 m.d(-1) mean training volume and 6 d.wk(-1)
      frequency; and a taper period (TP) of 1.5 weeks' duration that incorporated a 48%
      reduction in weekly volume without altering intensity. Attained swimming force
      (SF) and maximal performance over 200-m maximal swim (Pmax) before and after
      taper were measured. After taper, SF and Pmax improved 3.6 and 1.6%, respectively
      (p < 0.05). There were positive correlations (p < 0.05) between SF and Pmax
      before (r = 0.86) and after (r = 0.83) the taper phase. Peak lactate
      concentrations after SF were unaltered before (6.79 +/- 1.2 mM) and after (7.15
      +/- 1.8 mM) TP. Results showed that TP improved mean swimming velocity, but not
      in the same proportion as force after taper, suggesting that there are other
      factors influencing performance in faster swimming.

PMID- 17530933
TI  - Effects of six weeks of beta-hydroxy-beta-methylbutyrate (HMB) and HMB/creatine
      supplementation on strength, power, and anthropometry of highly trained athletes.
AB  - This study investigated the effects of 6 weeks of dietary supplementation of beta
      hydroxy-beta-methylbutyrate (HMB) and HMB combined with creatine monohydrate
      (HMBCr) on the muscular strength and endurance, leg power, and anthropometry of
      elite male rugby league players. The subjects were divided into a control group
      (n = 8), a HMB group (n = 11; 3 g.d(-1)) or a HMBCr group (n = 11; 12 g.d(-1)
      with 3 g HMB, 3 g Cr, 6 g carbohydrates). Three repetition maximum lifts on bench
      press, deadlifts, prone row, and shoulder press, maximum chin-up repetitions, 10
      second maximal cycle test, body mass, girths, and sum of skinfolds were assessed
      pre- and postsupplementation. Statistical analysis revealed no effect of HMB or
      HMBCr on any parameter compared with presupplementation measures or the control
      group. HMB and HMBCr were concluded to have no ergogenic effect on muscular
      strength and endurance, leg power, or anthropometry when taken orally by highly
      trained male athletes over 6 weeks.

PMID- 17530934
TI  - Relationships between selected muscle endurance tasks and gender.
AB  - The purpose of this research was to examine possible relationships between
      selected muscle endurance tasks and gender. Until 1990, girls' and women's
      programs infrequently contained activities such as sit-ups, push-ups, pull-ups,
      and exercises with resistance equipment. This lack of exposure may have, in turn,
      resulted in much poorer performance than men when examined in experimental
      settings. The results of a discriminant analysis indicated that the women (n =
      31) in this study did not differ from men (n = 31) in the mean number of sit-ups,
      modified push-ups, and leg adductions performed, but that the men performed more
      lateral arm raises than the women (p < 0.05). When the influence of the age,
      height, and weight of the subjects (mean +/- SD; 24.13 +/- 7.50 years, 173.05 +/-
      8.77 cm, 76.34 +/- 13.01 kg for men; 26.61 +/- 11.12 years, 161.82 +/- 6.47 cm,
      58.89 +/- 10.91 kg for women) was examined, there were only small changes in the
      structure of the discriminant function generated in the first analysis. These
      findings should be approached with caution because of possible limitations
      related to the size and representativeness of the sample and lack of measurement
      equipment such as video cameras. The fact that the pattern of results in this
      study differed somewhat from patterns in earlier research may indicate that the
      findings in this study are: (a) a random result or comparison anomaly related to
      characteristics specific to this convenience sample of women and men or (b)
      suggestive that differences between women and men in the tests chosen may be
      representative of changes that are beginning to occur in the degree of
      differences between men and women in college resistance training or other fitness
      related classes. Practical applications of the results of this study for teachers
      of resistance training or fitness-related classes in secondary school, college,
      and adult recreation might be that fitness programs should be individualized to
      meet needs specific to each student and that coeducational classes and programs
      should be expanded, especially offerings of fitness-related activities.

PMID- 17530935
TI  - Validation of a specific machine to the strength training of judokas.
AB  - With regard to judo players, like all sport activities, strength training can be
      divided into general and specific strength training. The specific exercises must
      correspond with the competitive movement. In addition, in terms of structure,
      they must correspond with regard to the strength time sequence, and they may be
      executed with overload. With respect to these important elements, we have
      envisaged the use of a judo-specific machine. The purpose of this study was to
      validate this judo-specific machine with regard to the strength training of
      judokas. To that end, we have measured the maximal pulling forces applied at each
      hand of judokas (n = 18), playing with the judo-specific machine and with a real
      partner. A significant difference was found between the maximal pulling forces (F
      collar and F sleeve) obtained utilizing the judo-specific machine (from 4.9 +/-
      0.4 N.kg(-1) to 6.4 +/- 0.3 N.kg(-1) for F collar; from 4.8 +/- 0.2 N.kg(-1) to
      6.3 +/- 0.3 N.kg(-1) for F sleeve) and performing with a partner (2.7 +/- 0.2
      N.kg(-1) for F collar; 2.5 +/- 0.3 N.kg(-1) for F sleeve). This can be explained
      by the fact that the partner opposes a low resistance during the judo-throwing
      technique in comparison with the judo-specific machine. These results show that
      the judo-specific machine might be used by the judokas to execute specific
      exercises with overload.

PMID- 17530936
TI  - Electromyographic activity of the trunk stabilizers during stable and unstable
      bench press.
AB  - The purpose of this study was to investigate the effectiveness of instability
      training in the recruitment of core stabilizing muscles during dynamic multijoint
      movement. Surface electromyography (EMG) was measured from 6 muscles (latissimus
      dorsi, rectus abdominus, internal obliques, erector spinae, and soleus) while
      subjects performed a 9.1-kg bench press on stable and unstable surfaces. There
      were 4 exercises in total: (a) stable surfaces for shoulders and feet, (b) upper
      body instability, (c) lower-body instability, and (d) dual instability. Five
      seconds of EMG were recorded during each bench press and were subsequently
      smoothed with root mean squares calculated for the entire time-series. A repeated
      measures analysis of variance (ANOVA) was used to test overall differences
      between exercise conditions for each muscle. Paired equal variance t-tests with a
      stepwise Bonferroni correction for multiple contrasts (alpha = 0.05/total number
      of contrasts) were performed for muscles with significant repeated-measures ANOVA
      results. The results show significant increases in EMG with increasing
      instability. Specifically, the dual instability bench press resulted in the
      greatest mean muscle activation of the 3 stability conditions, with single
      instability conditions being significantly greater than the stable condition.
      This pattern of results is consistent with the position that performing the bench
      press in a progressively unstable environment may be an effective method to
      increase activation of the core stabilizing musculature, while the upper- and
      lower-body stabilizers can be activated differentially depending on the mode of
      instability.

PMID- 17530937
TI  - Early-phase strength gains during traditional resistance training compared with
      an upper-body air-resistance training device.
AB  - The purpose of this study was to examine the early-phase adaptations of
      traditional dynamic constant external resistance (DCER) training vs. a portable
      upper-body training device (Fortex). The Fortex is a concentric training device
      based on air resistance. Contractions using this device are slow (1.5-3 s) and
      have a limited range of motion. The exercises potentially allow maximal muscle
      action during each contraction. Healthy, sedentary men (n = 30) were assigned to
      begin either 8 weeks of weight training (W, n = 12) or 8 weeks of Fortex training
      (F, n = 9), and were compared with a control group (C, n = 9). Exercises were
      chosen for the W group that would train similar muscle groups and contain a
      similar volume of repetitions as the F group. However, movement patterns and
      force curves were not identical. Increases in the upper-arm cross-sectional area
      were not detected in any of the groups. Both training groups showed strength
      gains in the various strength tests that were distinct from each other. Our
      results indicate that both Fortex and DCER training proved effective in eliciting
      strength gains in sedentary men over an 8-week training period. There are,
      however, limitations with the Fortex in terms of progression needs and training
      asymmetry that indicate it should be used as a complement to other training.

PMID- 17530938
TI  - The effect of interval training in children with exercise-induced asthma
      competing in soccer.
AB  - A lot of emphasis has been placed in screening individuals with exercise-induced
      bronchospasm in order to avoid persistence bronchial hyperactivity and consequent
      chronic silent inflammation of the respiratory tract. The purpose of this study
      was to evaluate the effect of interval training on the respiratory function and
      endurance in children with exercise-induced asthma (EIA) participating in the
      sport of soccer. Twenty-nine boys ages 10-14, who developed EIA after a 6-minute
      free running test (decline in forced expiratory volume in 1 second: FEV(1)10%),
      participated in the study. They were divided into 2 groups (experimental: n = 18,
      and control: n = 11), fulfilling the same criteria (i.e., age, body height and
      weight, and severity of asthma). The experimental group exercised with the
      interval training method for a period of 8 weeks, (3 sessions per week), whereas
      the control group exercised with the usual football program. Measurements were
      made for FEV(1) and endurance in both groups, before and after the application of
      training (8 weeks). Following the implementation of the training program, a
      significant improvement in FEV(1) and endurance was documented in the
      experimental group, as well as significant differences between the 2 groups. In
      conclusion, duration and aerobic training via the interval method seems to be
      beneficial to soccer players with EIA.

PMID- 17530939
TI  - A kinematic comparison of deep water running and overground running in endurance
      runners.
AB  - Deep water running (DWR) is commonly used as a rehabilitative tool or as a
      running specific cross-training modality. However, because little is known about
      the biomechanical specificity of this training, the aim of this study was to
      compare the leg kinematics of DWR vs. overground running (OGR). Five endurance
      runners' leg actions in the sagittal plane were filmed in 2 dimensions in DWR and
      OGR at slow (72 cycles.min(-1)) and fast (92 cycles.min(-1)) frequencies to
      measure hip and knee angles. Hip-knee angle-angle diagrams were quantified using
      cross-correlations (r). Leg motion was different between DWR and OGR both
      kinematically (e.g., hip maximum flexion angle, slow frequency: DWR = 92 +/- 20
      degrees ; OGR = 49 +/- 10 degrees ; p < 0.05) and in coordination (e.g., slow
      frequency: DWR, r = -0.94, lag = -1%; OGR, r = 0.87, lag = 22%). The time lag
      indicates that the hip and knee flex and extend together in DWR, whereas the hip
      moves before the knee during OGR. Stride frequency had an effect on OGR but not
      on DWR. The apparent differences between DWR and OGR are likely to affect muscle
      recruitment patterns and this could be problematic for athletes with hip and knee
      injuries. Because the negative effects of DWR as a rehabilitative tool are not
      known, gradual familiarization to DWR prior to a prescribed DWR rehabilitation or
      intense fitness maintenance program is recommended to offset any adverse affects.

PMID- 17530940
TI  - The effect of two warm-up protocols on some biomechanical parameters of the
      neuromuscular system of middle distance runners.
AB  - The objective of this study was to determine the effect of 2 different warm-up
      protocols on the neuromuscular system of well-trained middle distance runners.
      Seven runners performed 2 different warm-up protocols, one of which included slow
      running, stretching, and bounding and sprinting exercises, while the other
      consisted of slow running and stretching only. Before and after warm-up,
      contractile properties of the vastus lateralis and quadriceps femoris were
      monitored with a single twitch test, maximal torque, and the level of muscle
      activation during maximal voluntary extension. The 2 types of warm-up protocols
      showed statistically significant differences in the increase of peak knee
      extension torque and muscle activation level. After warm-up 1 maximal twitch
      torque was increased and twitch contraction time (CT) was shortened. Both maximal
      torque and the level of activation were increased. Parameter changes after warm
      up 2 were similar to those after warm-up 1 but not statistically significant.
      Sprinting and bounding as part of athletes' warm-up improve muscle activation.

PMID- 17530941
TI  - The effect of short-term use of testosterone enanthate on muscular strength and
      power in healthy young men.
AB  - Use of testosterone enanthate has been shown to significantly increase strength
      within 6-12 weeks of administration (2, 9), however, it is unclear if the
      ergogenic benefits are evident in less than 6 weeks. Testosterone enanthate is
      classified as a prohibited substance by the World Anti-Doping Agency (WADA) and
      its use may be detected by way of the urinary testosterone/epitestosterone (T/E)
      ratio (16). The two objectives of this study were to establish (a) if injection
      of 3.5 mg.kg(-1) testosterone enanthate once per week could increase muscular
      strength and cycle sprint performance in 3-6 weeks; and (b) if the WADA-imposed
      urinary T/E ratio of 4:1 could identify all subjects being administered 3.5
      mg.kg(-1) testosterone enanthate. Sixteen healthy young men were match-paired and
      were assigned randomly in a double-blind manner to either a testosterone
      enanthate or a placebo group. All subjects performed a structured heavy
      resistance training program while receiving either testosterone enanthate (3.5
      mg.kg(-1)) or saline injections once weekly for 6 weeks. One repetition maximum
      (1RM) strength measures and 10-second cycle sprint performance were monitored at
      the pre (week 0), mid (week 3), and post (week 6) time points. Body mass and the
      urinary T/E ratio were measured at the pre (week 0) and post (week 6) time
      points. When compared with baseline (pre), 1RM bench press strength and total
      work during the cycle sprint increased significantly at week 3 (p < 0.01) and
      week 6 (p < 0.01) in the testosterone enanthate group, but not in the placebo
      group. Body mass at week 6 was significantly greater than at baseline in the
      testosterone enanthate group (p < 0.01), but not in the placebo group. Despite
      the clear ergogenic effects of testosterone enanthate in as little as 3 weeks, 4
      of the 9 subjects in the testosterone enanthate group ( approximately 44%) did
      not test positive to testosterone under current WADA urinary T/E ratio criteria.

PMID- 17530942
TI  - The effect of five weeks of Tribulus terrestris supplementation on muscle
      strength and body composition during preseason training in elite rugby league
      players.
AB  - Tribulus terrestris is an herbal nutritional supplement that is promoted to
      produce large gains in strength and lean muscle mass in 5-28 days (15, 18).
      Although some manufacturers claim T. terrestris will not lead to a positive drug
      test, others have suggested that T. terrestris may increase the urinary
      testosterone/epitestosterone (T/E) ratio, which may place athletes at risk of a
      positive drug test. The purpose of the study was to determine the effect of T.
      terrestris on strength, fat free mass, and the urinary T/E ratio during 5 weeks
      of preseason training in elite rugby league players. Twenty-two Australian elite
      male rugby league players (mean +/- SD; age = 19.8 +/- 2.9 years; weight = 88.0
      +/- 9.5 kg) were match-paired and randomly assigned in a double-blind manner to
      either a T. terrestris (n = 11) or placebo (n = 11) group. All subjects performed
      structured heavy resistance training as part of the club's preseason
      preparations. A T. terrestris extract (450 mg.d(-1)) or placebo capsules were
      consumed once daily for 5 weeks. Muscular strength, body composition, and the
      urinary T/E ratio were monitored prior to and after supplementation. After 5
      weeks of training, strength and fat free mass increased significantly without any
      between-group differences. No between-group differences were noted in the urinary
      T/E ratio. It was concluded that T. terrestris did not produce the large gains in
      strength or lean muscle mass that many manufacturers claim can be experienced
      within 5-28 days. Furthermore, T. terrestris did not alter the urinary T/E ratio
      and would not place an athlete at risk of testing positive based on the World
      Anti-Doping Agency's urinary T/E ratio limit of 4:1.

PMID- 17530943
TI  - Effects of acute upper-body vibration on strength and power variables in
      climbers.
AB  - Whole-body vibration training has recently received a lot of attention with
      reported enhancements of strength and power qualities in athletes. This study
      investigated whether upper-body vibration would be able to augment muscular
      attributes for climbing performance. Twelve healthy active climbers volunteered
      for the study. All participants underwent 3 treatments--arm cranking (AC), upper
      body vibration (UBV), and non-UBV (NUBV)--in a balanced random order, conducted
      on separate days. Upper-body vibration was generated via a commercialized
      electric-powered dumbbell with a rotating axis that delivered oscillatory
      movements to the shoulders and arms. The UBV treatment consisted of performing 5
      upper-body exercises for a total duration of 5 minutes. The UBV frequency was set
      at 26 Hz, amplitude 3 mm. For the NUBV treatment, the participants performed the
      exact exercises and time constraints as UBV; however, the vibration dumbbell was
      set at 0 Hz and 0 mm amplitude. The third treatment consisted of AC, which was
      performed at 75 k.min(-1) for 5 minutes. Pre- and postmuscular performance
      measures of medicine ball throw, hand grip strength, and a specific climbing
      maneuver were performed after each treatment. There were no significant treatment
      differences on medicine ball throw, hand grip strength, and the specific climbing
      maneuver. Acute UBV exposure did not demonstrate the expected potential
      neuromuscular enhancements on the climbing performance tests selected for this
      study.

PMID- 17530944
TI  - Acute effects of augmented eccentric loading on jump squat performance.
AB  - The purpose of this study was to determine the acute effects of a spectrum of
      eccentric loads on force, velocity, and power during the concentric portion of
      maximal-effort jump squats utilizing a repeated measures design. Thirteen
      resistance-trained men (age = 22.8 +/- 2.9 years, weight = 87.1 +/- 11.8 kg,
      163.5 +/- 28.6 kg squat 1 repetition maximum [1RM]; mean +/- SD), who routinely
      incorporated back squats into their training, participated as subjects in this
      investigation. Jump squat performance was assessed using 4 experimental
      conditions. The first of these conditions consisted of an isoinertial load equal
      to 30% of back squat 1RM. The remaining conditions consisted of jump squats with
      a concentric load of 30% 1RM, subsequent to the application of experimental
      augmented eccentric loading (AEL) conditions of 20, 50, and 80% of back squat
      1RM, respectively. All subjects performed 2 sets of 1RM of maximum-effort jump
      squats with all experimental conditions in a counter-balanced sequence. Forty
      eight hours after completing the first testing session, subjects repeated the
      experimental testing protocol to establish stability reliability. Peak
      performance values for the reliable variables of force, velocity, and power, as
      well as force and power values obtained at 20-ms intervals during the initial 400
      ms of the concentric jump squat range of motion, showed no statistical difference
      (p > 0.05) across the experimental AEL loads. These results suggest that load
      spectrum AEL prior to a 30% 1RM jump squat fails to acutely enhance force,
      velocity, and power.

PMID- 17530945
TI  - Perceptions and attitudes toward androgenic-anabolic steroid use among two age
      categories: a qualitative inquiry.
AB  - We attempted to qualitatively investigate why men of 2 age categories have chosen
      not to use androgenic-anabolic steroids (AASs). Twelve men (22.28 +/- 1.38 years
      [group I] and 53.00 +/- 13.28 years [group II]) were selected on the basis of
      specific inclusion criteria, including age and fitness levels (i.e., "do you
      weight train?"). Subjects were classified in 1 of 2 categories-younger or older
      precluders-and were asked to complete 2 survey instruments before their
      participation. The Drive for Muscularity Scale (reliability 0.85) and Body Image
      Questionnaire were used to gain a better understanding of perceptions and
      motivations regarding health, fitness, and body image. A series of semistructured
      questions were used to enhance focus group discussion regarding attitudes.
      Questions were validated by a panel of experts in qualitative methods. Member
      checks were conducted to enhance trustworthiness of the data. Data were
      transcribed verbatim and analyzed with thematic open-coding techniques. Various
      behaviors were reported regarding body image. Emerging themes showed a clear
      demarcation between age categories. Younger subjects cited power, control, body
      image, and narcissism, whereas older subjects viewed AAS use as more of an
      athletic-based phenomenon, such as with performance enhancement, when asked about
      steroids. Groups were in agreement that media trends and perceptions of the ideal
      male body are becoming "superhuman" and unattainable without chemical means.
      Understanding attitudinal perspectives might help complement national data on AAS
      trends. Future investigations could help coaches and allied health professionals
      collaborate with each other, as well as with national groups and foundations, to
      devise more appropriate strategies in addressing this growing athletic and public
      health concern.

PMID- 17530946
TI  - Influence of type of muscle contraction, gender, and lifting experience on
      postactivation potentiation performance.
AB  - Postactivation potentiation (PAP) or enhanced contractile capabilities may be
      influenced by a number of factors. This study examined the influence of type of
      muscle contraction (isometric vs. dynamic), gender, and previous weightlifting
      experience on PAP as demonstrated by changes in jump height and power output.
      Thirty young men (n = 15) and women (n = 15), classified as either having
      previous weightlifting experience (n = 20) or not (n = 10), performed 3 different
      sets of countermovement jumps, with the first set used to determine baseline
      measures of jump height and power. The second set was performed after a maximal
      isometric squat protocol (maximal voluntary contraction [MVC]-PAP) to induce PAP,
      and the third set of jumps was performed after a maximal dynamic squat (DS)
      protocol (DS-PAP). A 3-way repeated measures analysis of variance determined that
      jump height after the MVC-PAP protocol was significantly higher than both the
      pretest and DS-PAP values, that men performed significantly better than women,
      and that the experienced lifters responded more favorably than the inexperienced
      lifters. Jump power was also significantly greater for the MVC-PAP condition
      compared with the other 2 conditions, and DS-PAP power also improved when
      compared with the pretest values, with men performing significantly better than
      women. All results remained consistent after accounting for height and weight
      differences (body mass index) between the groups. In conclusion, the isometric
      condition (MVC-PAP) evoked a greater muscle postactivation potentiation than the
      dynamic condition (DS-PAP), and postactivation was enhanced by previous
      weightlifting experience. The practical manipulation of MVC by pushing,
      squatting, or both against fixed objects, such as walls and low ceilings, could
      be a very simple and cost-effective way to arouse a state of PAP before sports
      performance that requires high force and power outputs.

PMID- 17530947
TI  - Effect of six weeks of dura disc and mini-trampoline balance training on postural
      sway in athletes with functional ankle instability.
AB  - Lateral ankle sprain (LAS) is one of the most common injuries incurred during
      sporting activities, and effective rehabilitation programs for this condition are
      challenging to develop. The purpose of this research was to compare the effect of
      6 weeks of balance training on either a mini-trampoline or a dura disc on
      postural sway and to determine if the mini-trampoline or the dura disc is more
      effective in improving postural sway. Twenty subjects (11 men, 9 women) with a
      mean age of 25.4 +/- 4.2 years were randomly allocated into a control group, a
      dura disc training (DT) group, or a mini-trampoline (MT) group. Subjects
      completed 6 weeks of balance training. Postural sway was measured by subjects
      performing a single limb stance on a force plate. The disbursement of the center
      of pressure was obtained from the force plate in the medial-lateral and the
      anterior-posterior sway path and was subsequently used for pretest and posttest
      analysis. After the 6-week training intervention, there was a significant (p <
      0.05) difference in postural sway between pre- and posttesting for both the MT
      (pretest = 56.8 +/- 20.5 mm, posttest = 33.3 +/- 8.5 mm) and DT (pretest = 41.3
      +/- 2.6 mm, posttest = 27.2 +/- 4.8 mm) groups. There was no significant (p >
      0.05) difference detected for improvements between the MT and DT groups. These
      results indicate that not only is the mini-trampoline an effective tool for
      improving balance after LAS, but it is equally as effective as the dura disc.

PMID- 17530948
TI  - Influence of vibration training on energy expenditure in active men.
AB  - The aim of the present study was to analyze the effect of whole-body vibration on
      energy expenditure, as well as on exercise intensity, during and immediately
      after a typical set of exercises for muscle hypertrophy in physically active
      subjects. Seventeen male university students (mean age 18.3 +/- 0.24 years)
      volunteered to perform 2 different training exercises: half squat (HS), and half
      squat with vibration (HSV). Both exercises were performed by all subjects on the
      vibration platform (with vibration only for HSV), the sequence order being
      assigned randomly. Energy expenditure (EE), respiratory exchange ratio, perceived
      exertion (PE), and heart rate were recorded for baseline, exercise, and short
      recovery conditions. Training consisted of 5 sets of 10 repetitions of HS and
      HSV, with a 2-minute recovery interval between sets. Analysis of variance with
      repeated measurements and Bonferroni correction, as well as effect size were used
      for statistical calculations. Results indicated that EE and PE were significantly
      higher in the HSV group, during both exercise and recovery. Heart rate did not
      differ significantly between groups. Thus, it would appear that HS strength
      training could be rendered more energy-efficient through the addition of
      vibration. Moreover, it would be feasible to introduce vibration exercises into
      regular training programs, particularly those whose key objective is muscle
      hypertrophy along with fat reduction.

PMID- 17530949
TI  - Reliability and validity of the performance index evaluation among men's and
      women's college basketball players.
AB  - The Performance Index Evaluation (PIE) is a basketball-specific assessment of
      physical performance. The battery consists of items typically included in sport
      assessments, such as agility and power, but also addresses an often-overlooked
      performance component, namely, core strength. The purpose of this study was to
      examine the reliability (test-retest, interrater), validity (criterion-related,
      construct-related), and practice effect of the PIE among men's and women's
      college basketball players. Test-retest estimates were moderate for men
      (intraclass correlation coefficient [ICC] = 0.79) and poor for women (ICC =
      0.35), but interrater reliability was high (ICC = 0.95). Criterion-related
      validity evidence (i.e., relationship between PIE and playing time) was weak, but
      construct-related evidence was acceptable (i.e., college players had higher
      scores than high school players). A practice effect was also demonstrated among
      men. In conclusion, reliability of the battery should be improved before its use
      is recommended among college basketball players. Additionally, the battery does
      not appear to be a predictor of performance but does appear to distinguish
      between skill levels.

PMID- 17530950
TI  - The effect of acute moderate hypoxia on accumulated oxygen deficit during
      intermittent exercise in nonacclimatized men.
AB  - The objective of this study was to determine the effect of acute moderate hypoxia
      and rest duration on performance and on the accumulated oxygen deficit (AOD) in
      high-intensity intermittent efforts. After preliminary tests, 2 groups of
      nonacclimatized men (resident at 690 m above sea level) carried out 3 randomized
      protocols of effort (EXP1, EXP2, and EXP5) on 3 different days. These tests were
      performed at acute moderate altitude (2,320 m) by the hypoxia group (H) and in
      normoxia by the normoxia group (N). During EXP1 the subjects ran a maximum of
      five 400-m sprints (90% intensity) on a treadmill, with a pause between efforts
      of 1 minute. In EXP2 and EXP5 the same protocol was repeated, increasing the rest
      period between sprints to 2 and 5 minutes, respectively. Lactate accumulation and
      exhaled gases were measured during the tests. Accumulated oxygen deficit was
      calculated for each sprint. The total AOD (SigmaAOD) for each type of protocol
      was determined to be the sum of the corresponding accumulated deficits. The AODs
      were influenced by the length of rest period (p < 0.05) but not by H. The
      increase in recovery time between sprints increased the SigmaAOD (7,843 +/- 4,435
      vs. 7,137 +/- 2,117 ml; 11,013 +/- 4,616 vs. 9,931 +/- 2,731 ml; 12,611 +/- 4,594
      vs. 12,907 +/- 3,085 ml for H and N in EXP1, EXP2, and EXP5, respectively). The
      AOD increased in value when the same sprint was compared from EXP1 to EXP5 (p <
      0.05). The results obtained show that exposure to acute moderate altitude does
      not affect the anaerobic pathway contribution in intermittent high-intensity
      exercises. Performance during this type of repeated effort is not altered during
      acute exposure to moderate altitude, which should be taken into account when an
      acclimatizing period is not possible.

PMID- 17530951
TI  - A comparison of lower-body flexibility, strength, and knee stability between
      karate athletes and active controls.
AB  - The purposes of this study were to compare the lower-body flexibility, strength,
      and knee stability of karate athletes against that of non-karate controls and to
      determine whether regular karate training results in adaptations that may result
      in an increased risk for knee injury. Flexibility measurements included knee
      flexion and extension, hip flexion and extension, hip internal and external
      rotation, and foot inversion and eversion. Nine karate athletes (4 women and 5
      men, age = 24.3 +/- 6.7 years) and 15 active, non-karate controls (7 women and 8
      men, age = 22.1 +/- 3.2 years) participated. No subjects reported recent knee
      surgery or chronic or acute knee pain. Concentric quadriceps and hamstrings
      strength and endurance were measured using a Biodex II isokinetic dynamometer at
      60 degrees .s(-1) and 180 degrees .s(-1). Eccentric strength was measured at 150
      degrees .s(-1) and 250 ft-lb (339 N.m). Knee stability was measured via varus and
      valgus stress and anterior drawer testing. Karate athletes demonstrated a
      significantly greater right hip flexion (p <or= 0.05). Isokinetic testing
      demonstrated a significantly greater concentric right and left hamstrings peak
      torque at 60 degrees .s(-1), right hamstrings to quadriceps torque ratio at both
      60 degrees .s(-1) and 180 degrees .s(-1), and a significantly faster time to peak
      torque in the hamstrings at 60 degrees .s(-1) in the karate athletes (p <or=
      0.05). Eccentric isokinetic testing showed a significantly higher peak torque at
      60 degrees .s(-1) in both the right and left quadriceps and hamstrings in the
      karate group compared to the controls (p <or= 0.05). There were no significant
      differences in bilateral movement of the knees between the karate and control
      groups. The results indicate that this group of karate athletes may have
      demonstrated sport-specific adaptations in certain flexibility and strength
      measurements, but they showed no increased risk for knee injury.

PMID- 17530952
TI  - Physiological and performance characteristics of adolescent club volleyball
      players.
AB  - The objective of this investigation was to examine the physical and performance
      characteristics of adolescent club volleyball players. Twenty-nine adolescent
      girls, aged 12 to 17 years (14.31 +/- 1.37) were participants in this
      investigation. All athletes were members of a competitive volleyball club. The
      following group values were obtained: height (HT) = 1.69 +/- 0.08 m, weight (WT)
      = 59.6 +/- 8.2 kg, body fat percentage (BF%) = 20.9 +/- 4.5, lean body mass (LBM)
      = 46.7 +/- 4.9 kg, modified sit-and-reach (MSR) = 38.7 +/- 7.1 cm, shoulder
      rotation (SR) = 29.4 +/- 5.6 cm, isometric hand grip (IHG) = 34.5 +/- 5.5 kg,
      isometric leg strength (ILS) = 77.4 +/- 18.1 kg, vertical jump (VJ) = 35.5 +/-
      6.2 cm, standing broad jump (SBJ) =178.8 +/- 20.3 cm, 1-minute sit-ups (SU) =
      47.0 +/- 6.7, T-test (TT) = 11.2 +/- 0.8 seconds., shuttle test (SHT) = 9.7 +/-
      0.4 seconds, stork stand (SS) = 8.1 +/- 4.1 seconds, serving velocity (SVV) =16.1
      +/- 4.5 m.s(-1), and spiking velocity (SKV) = 16.9 +/- 2.4 m.s(-1). For purposes
      of analysis, players were divided into 2 age groups: 12 to 14 years (group A) and
      15 to 17 years (group B). Significant differences (p < 0.05) were found between
      age groups for the following values: HT, WT, LBM, IHG, ILS, SBJ, and SVV. Values
      for group B were greater for each variable. Significant correlations include age
      and IHG (r = 0.75), age and ILS (r = 0.51), age and SBJ (r = 0.67), age and SVV
      (r = 0.71), LBM and IHG (r = 0.90), LBM and ILS (r = 0.62), LBM and SVV (r =
      0.58), SVV and IHG (r = 0.60), and SKV and SS (r = 0.60). Our results suggest
      that age, experience, LBM, shoulder, hip, and thigh girths, strength, and balance
      are key physical performance characteristics of adolescent girls who play
      volleyball. Potentially, this type of information will allow coaches and athletes
      to identify physical and performance data specific to age groups for purposes of
      evaluation and player development.

PMID- 17530953
TI  - Reliability and detecting change following short-term creatine supplementation:
      comparison of two-component body composition methods.
AB  - The purpose of the present study was twofold: firstly, to assess the reliability
      of various body composition methods, and secondly, to determine the ability of
      the methods to estimate changes in fat-free mass (FFM) following creatine (Cr)
      supplementation. Fifty-five healthy male athletes (weight 78.3 +/- 10.3 kg, age
      21 +/- 1 years) gave informed consent to participate in this study. Subjects' FFM
      was estimated by hydrostatic weighing (HW), air-displacement plethysmography
      (ADP), bioelectrical impedance analysis (BIA), near-infrared spectroscopy (NIR),
      and anthropometric measurements (ANTHRO). Measurements were taken on 2 occasions
      separated by 7 days to assess the reliability of the methods. Following this, 30
      subjects returned to the laboratory for an additional test day following 7 days
      of Cr supplementation (20 g.d(-1) Cr + 140 g.d(-1) dextrose) to assess each
      method's ability to detect acute changes in FFM. In terms of reliability, we
      found excellent test-retest correlations for all 5 methods, ranging from 0.983 to
      0.998 (p < 0.001). The mean biases for the 5 methods were close to 0 (range -0.1
      to 0.3 kg) and their 95% limits of agreement (LOAs) were within acceptable limits
      (HW = -1.1 to 1.7 kg; ADP = -1.1 to 1.2 kg; BIA = -1.0 to 1.0 kg; NIR = -1.4 to
      1.4 kg); however, the 95% LOAs were slightly wider for ANTHRO (-2.4 to 2.6 kg).
      Following Cr supplementation there was a significant increase in body mass (from
      77.9 +/- 10.1 kg to 78.9 +/- 10.3 kg, p = 0.000). In addition, all 5 body
      composition techniques detected the change in FFM to a similar degree (mean
      change: HW = 0.9 +/- 0.6 kg; ADP = 0.9 +/- 0.6 kg; BIA = 0.9 +/- 0.6 kg; NIR =
      0.8 +/- 0.5 kg; ANTHRO = 1.0 +/- 0.7 kg; intraclass correlation coefficient =
      0.962). We conclude that between-day differences in FFM estimation were within
      acceptable limits, with the possible exception of ANTHRO. In addition, all 5
      methods provided similar measures of FFM change during acute Cr supplementation.

PMID- 17530954
TI  - Effects of electromyostimulation training on muscle strength and power of elite
      rugby players.
AB  - The present study investigated the influence of a 12-week electromyostimulation
      (EMS) training program performed by elite rugby players. Twenty-five rugby
      players participated in the study, 15 in an electrostimulated group and the
      remaining 10 in a control group. EMS was conducted on the knee extensor, plantar
      flexor, and gluteus muscles. During the first 6 weeks, training sessions were
      carried out 3 times a week and during the last 6 weeks, once a week. Isokinetic
      torque of the knee extensors was determined at different eccentric and concentric
      angular velocities ranging from -120 to 360 degrees .s(-1). Scrummaging and full
      squat strength, vertical jump height and sprint-running times were also
      evaluated. After the first 6 weeks of EMS, only the squat strength was
      significantly improved (+8.3 +/- 6.5%; p < 0.01). After the 12th week, the -120
      degrees .s(-1) maximal eccentric, 120 and 240 degrees .s(-1) maximal concentric
      torque (p < 0.05), squat strength (+15.0 +/- 8.0%; p < 0.001), squat jump (+10.0
      +/- 9.5%; p < 0.01), and drop jump from a 40-cm height (+6.6 +/- 6.1%; p < 0.05)
      were significantly improved. No significant change was observed for the control
      group. A 12-week EMS training program demonstrated beneficial effects on muscle
      strength and power in elite rugby players on particular tests. However, rugby
      skills such as scrummaging and sprinting were not enhanced.

PMID- 17530955
TI  - Simple anthropometric and physical performance tests to predict maximal box
      lifting ability.
AB  - Box-lifting ability is an important characteristic of military personnel. The
      purpose of this paper was to determine the usefulness of the upright row free
      weight exercise and simple anthropometric tests to predict maximal box-lifting
      performance that simulates the loading of military supply vehicles. Two groups of
      adults performed maximal box lifts to 1.4 m (study 1) and 1.7 m (study 2),
      respectively. All subjects were also tested for upright row 1 repetition maximum
      (1RM) strength, body mass, height, and body composition. In study 1, a remarkably
      good prediction of maximal box-lift performance to 1.4 m (42 +/- 12 kg) was
      obtained from a regression equation including the variables body mass, body
      composition, and upright row 1RM. Approximately 95% of the variation in 1.4-m box
      lifting performance could be accounted for. In contrast, in study 2, only 80% of
      the variation in 1.7-m box-lifting performance (51 +/- 15 kg) could be accounted
      for by the best predictor equation. Upright row 1RM strength appears to be a
      useful tool in the prediction of box-lifting ability to approximately chest
      height for most adults, probably due to a close match between the muscle groups
      and contraction modes required during both tasks. Military or other organizations
      could use the data reported here to substitute simple anthropometry and a 1RM
      test of strength and for the direct assessment of 1.4-m box-lifting performance.

PMID- 17530956
TI  - The cardiorespiratory, anthropometric, and performance characteristics of an
      international/national touring ballet company.
AB  - This study examined the cardiorespiratory and anthropometric indices of
      professional classical ballet dancers in relation to company seniority, gender,
      and supplemental training. Forty-nine participants from an international touring
      company carried out a peak Vo(2) test and vertical jump test. Anthropometric
      measurements and supplemental training activities were also recorded for each
      participant. Statistical analyses showed significant differences between gender
      and dancer seniority levels. Gender differences were seen for jump height (M =
      52.7 +/- 7.12 cm; F = 37.6 +/- 5.32 cm) and peak Vo(2) (M = 49.32 +/- 3.72 ml.kg(
      1).min(-1); F = 43.3 +/- 5.16 ml.kg(-1).min(-1)). Differences were also seen
      between dancer levels for peak Vo(2) (artist = 46.47 +/- 4.67 ml.kg(-1).min(-1);
      first artist = 42.72 +/- 5.81 ml.kg(-1).min(-1); soloist = 43.38 +/- 7.14 ml.kg(
      1).min(-1); principal = 49.04 +/- 3.63 ml.kg(-1).min(-1)) and jump height (artist
      = 42.0 +/- 9.11 cm; first artist = 50.33 +/- 11.65 cm; soloist = 45.6 +/- 9.78
      cm; principal = 44.67 +/- 9.53 cm). Pairwise post hoc comparisons showed that
      corps and principals had significantly greater relative peak Vo(2) than first
      artists and soloists (p < 0.05), while soloists and first artists had
      significantly greater jump heights compared to principals and corps (p < 0.05).
      Analysis of covariance modeling indicated that the self-reported mode of
      supplemental training had no association with relative peak Vo(2) or the
      percentage at which ventilatory threshold occurred. The present study has
      provided further insight into the cardiorespiratory profiles of classical ballet
      dancers, where soloists have significantly greater power capacities compared to
      principals and corps, who in turn had significantly greater aerobic power. These
      data can help guide strength and conditioning intervention strategies that need
      to take into account the nuances of the different seniority levels within a dance
      company.

PMID- 17530957
TI  - Measures of exercise intensity during soccer training drills with professional
      soccer players.
AB  - Recent evidence supports the use of certain soccer drills for combined technical
      and physical training. Therefore, it is important to be able to accurately
      monitor training intensity during soccer drills intended for physical development
      to allow the optimization of training parameters. Twenty-eight professional
      soccer players were assessed for heart rate (HR) and rating of perceived exertion
      (RPE) responses to 5 commonly used soccer training drills (2v2 to 8v8 drills).
      The responses of both HR and RPE differed significantly (p < 0.05) between the
      drills, generally showing an elevated response to drills involving lower player
      numbers. However, the 2v2 drill showed a significantly (p < 0.05) lower HR
      response (mean +/- SD: 88.7 +/- 1.2% HRmax) than 3v3 (91.2 +/- 1.3% HRmax) and
      4v4 drills (90.2 +/- 1.6% HRmax). There was no significant correlation between
      the HR and RPE responses to the various drills (r = 0.60, p = 0.200). This poor
      relationship is probably because during the 2v2 drill, RPE was higher than during
      any of the other 6 drills, whereas HR was only fourth highest of the 6 drills.
      This demonstrates that HR and RPE are only poorly related during the intense
      drills used in this study, and that HR underestimates the intensity of the 2v2
      drill. Heart rate demonstrated lower intersubject variability (1.3-2.2%) than RPE
      (5.1-9.9%). However, unlike HR, Borg 15-point RPE appears to be a valid marker of
      exercise intensity over a wide range of soccer training drills by maintaining
      validity in all drills and demonstrating acceptable intersubject variability. A
      combination of both HR- and RPE-based training load calculations appears optimal
      for use in soccer training.

PMID- 17530958
TI  - Prehabilitation before knee arthroplasty increases postsurgical function: a case
      study.
AB  - Conditioning the body to undergo physical stress such as joint arthroplasty has
      been termed prehabilitation. This case study examined the effect of a 4-week
      prehabilitation intervention on functional outcomes after total knee arthroplasty
      (TKA). Two female subjects completed baseline strength and functional assessments
      before TKA. Subjects were randomized to either a 4-week prehabilitation
      intervention (ES) aimed at increasing strength and range of motion or a usual
      care condition (CS). After 4 weeks of training, subjects were reassessed and
      underwent TKA. Subjects completed a final assessment 12 weeks after TKA.
      Functional outcomes included 6-minute walk, number of times up from a chair in 30
      seconds, proprioception, and self-reported function and pain using the Western
      Ontario and McMaster Universities Osteoarthritis Index. The data suggest that 4
      weeks of prehabilitation had a positive effect on functional task performance and
      knee proprioception before surgery. After surgery, the ES continued to exhibit
      higher levels of functioning and less pain compared with the CS. Prehabilitation
      before TKA may contribute to improved recovery after surgery.

PMID- 17530959
TI  - Effect of competitiveness on forty-yard dash performance in college men and
      women.
AB  - The objective of this study was to determine performance differences between
      individual and competitive trials of the 40-yard dash. Physically active college
      men (n = 25) and women (n = 29) performed an individual 40-yard dash, followed by
      completion of the Sports Competition Trait Inventory (SCTI) before performing a
      paired 40-yard dash against a time-matched competitor. All sprints were performed
      on an indoor rubberized track using photoelectric gates to start and stop a
      digital timer. In addition, 3 timers used hand-held stopwatches to record the
      individual sprint time. There was no significant difference (p = 0.10) between
      men (120.3 +/- 16.6) and women (111.7 +/- 20.3) on the SCTI. There was no
      significant difference between individual and competitive 40-yard dash times for
      either men (5.21 +/- 0.24 and 5.19 +/- 0.23 seconds, respectively) or women (6.12
      +/- 0.31 and 6.11 +/- 0.32 seconds, respectively). The correlation between SCTI
      and both individual and competitive 40-yard dashes was significant (p < 0.05) for
      women (r = -0.45 and -0.44, respectively) but not for men (r = -0.10 and 0.10,
      respectively). Electronic times (5.70 +/- 0.54 seconds) were not significantly
      different from 1 hand-timer (5.71 +/- 0.56 seconds) but were significantly faster
      than the other 2 timers (5.80 +/- 0.58 and 5.82 +/- 0.57 seconds). Averaging the
      3 hand times (5.78 +/- 0.56 seconds) for comparison with the electronic timing
      (5.70 +/- 0.54 seconds) produced a high correlation (r = 0.96) but a
      significantly slower time (p < 0.05). A competitive environment does not appear
      to improve short sprint times in either men or women. In addition, hand timing
      may not always produce faster times compared to electronic timing.

PMID- 17530960
TI  - Effects of sprint and plyometric training on muscle function and athletic
      performance.
AB  - The purpose of this study was to evaluate the effects of sprint training on
      muscle function and dynamic athletic performance and to compare them with the
      training effects induced by standard plyometric training. Male physical education
      students were assigned randomly to 1 of 3 groups: sprint group (SG; n = 30),
      plyometric group (PG; n = 30), or control group (CG; n = 33). Maximal isometric
      squat strength, squat- and countermovement jump (SJ and CMJ) height and power,
      drop jump performance from 30-cm height, and 3 athletic performance tests
      (standing long jump, 20-m sprint, and 20-yard shuttle run) were measured prior to
      and after 10 weeks of training. Both experimental groups trained 3 days a week;
      SG performed maximal sprints over distances of 10-50 m, whereas PG performed
      bounce-type hurdle jumps and drop jumps. Participants in the CG group maintained
      their daily physical activities for the duration of the study. Both SG and PG
      significantly improved drop jump performance (15.6 and 14.2%), SJ and CMJ height
      ( approximately 10 and 6%), and standing long jump distance (3.2 and 2.8%),
      whereas the respective effect sizes (ES) were moderate to high and ranged between
      0.4 and 1.1. In addition, SG also improved isometric squat strength (10%; ES =
      0.4) and SJ and CMJ power (4%; ES = 0.4, and 7%; ES = 0.4), as well as sprint
      (3.1%; ES = 0.9) and agility (4.3%; ES = 1.1) performance. We conclude that short
      term sprint training produces similar or even greater training effects in muscle
      function and athletic performance than does conventional plyometric training.
      This study provides support for the use of sprint training as an applicable
      training method of improving explosive performance of athletes in general.

PMID- 17530961
TI  - Methodological concerns for determining power output in the jump squat.
AB  - The purpose of this study was to investigate the validity of power measurement
      techniques during the jump squat (JS) utilizing various combinations of a force
      plate and linear position transducer (LPT) devices. Nine men with at least 6
      months of prior resistance training experience participated in this acute
      investigation. One repetition maximums (1RM) in the squat were determined,
      followed by JS testing under 2 loading conditions (30% of 1RM [JS30] and 90% of
      1RM [JS90]). Three different techniques were used simultaneously in data
      collection: (a) 1 linear position transducer (1-LPT); (b) 1 linear position
      transducer and a force plate (1-LPT + FP); and (c) 2 linear position transducers
      and a force place (2-LPT + FP). Vertical velocity-, force-, and power-time curves
      were calculated for each lift using these methodologies and were compared. Peak
      force and peak power were overestimated by 1-LPT in both JS30 and JS90 compared
      with 2-LPT + FP and 1-LPT + FP (p <or= 0.05). Peak power determined by 2-LPT + FP
      was significantly higher than that determined by 1-LPT + FP under the JS90
      loading condition. Peak vertical velocity determined by 2-LPT + FP was
      significantly lower than that determined by either 1-LPT and 1-LPT + FP in JS90.
      This investigation indicates that peak power and the timing of power output in
      the jump squat varies according to the measurement technique utilized. The 1-LPT
      methodology is not a valid means of determining power output in the jump squat.
      Furthermore, the 1-LPT + FP method may not accurately represent power output in
      free weight movements that involve a significant amount of horizontal motion.

PMID- 17530962
TI  - Kinematic responses to plyometric exercises conducted on compliant and
      noncompliant surfaces.
AB  - Jumping is an important performance component of many sporting activities. A
      number of training modalities have been used to enhance jumping performance
      including plyometrics. The positive effects of plyometric training on jumping
      performance are a function of the stretch-shortening cycle phenomenon. However,
      there has been little research on the effects of the surface on jumping
      performance. This study examined the effects of performing 2 different plyometric
      exercises, depth jump (DJ) and counter movement jump (CMJ), on noncompliant
      (ground) and compliant (mini-trampoline) surfaces. Male participants (N = 20; age
      = 21.8 +/- 3.8 years; height = 184.6 +/- 7.6 cm; mass = 83.6 +/- 8.2 kg) randomly
      performed 10 CMJ and 10 DJ on compliant and noncompliant surfaces. Kinematic data
      were determined via 2-dimensional high-speed video. There were significant (p <
      0.05) differences in DJ and CMJ joint and segment range of movement for ankle,
      knee, hip and trunk, indicating less crouch when the participants performed
      plyometric exercises on the compliant surface.

PMID- 17530963
TI  - Effects of dry-land vs. resisted- and assisted-sprint exercises on swimming
      sprint performances.
AB  - This study was undertaken to compare the effects of dry-land strength training
      with a combined in-water resisted- and assisted-sprint program in swimmer
      athletes. Twenty-one swimmers from regional to national level participated in
      this study. They were randomly assigned to 3 groups: the strength (S) group that
      was involved in a dry-land strength training program where barbells were used,
      the resisted- and assisted-sprint (RAS) group that got involved in a specific
      water training program where elastic tubes were used to generate resistance and
      assistance while swimming, and the control (C) group which was involved in an
      aerobic cycling program. During 12 weeks, the athletes performed 6 training
      sessions per week on separate days. All of them combined the same aerobic
      dominant work for their basic training in swimming and running with their
      specific training. Athletes were evaluated 3 times: before the training program
      started, after 6 weeks of training, and at the end of the training program. The
      outcome values were the strength of the elbow flexors and extensors evaluated
      using an isokinetic dynamometer, and the speed, stroke rate, stroke length, and
      stroke depth observed during a 50-meter sprint. No changes were observed after 6
      weeks of training. At the end of the training period, we observed significant
      increases in swimming velocity, and strength of elbow flexors and extensors both
      in the S and RAS groups. However, stroke depth decreased both in the S and RAS
      groups. Stroke rate increased in the RAS but not in the S group. However, no
      significant differences in the swimming performances between the S and RAS groups
      were observed. No significant changes occurred in C. Altogether, programs
      combining swimming with dry-land strength or with in-water resisted- and assisted
      sprint exercises led to a similar gain in sprint performance and are more
      efficient than traditional swimming training methods alone.

PMID- 17530964
TI  - Effects of aerobic training prior to and during chemotherapy in a breast cancer
      patient: a case study.
AB  - Treatment for breast cancer patients includes surgical removal of the tumor
      followed by chemotherapy. Chemotherapy frequently results in difficult to manage
      symptoms that threaten compliance with the therapy. Symptoms include fatigue,
      declines in functional ability, muscle wasting, and a decreased quality of life.
      Preparing the body to tolerate a stressful event such as chemotherapy has been
      termed "prehabilitation". This case study determined the efficacy of introducing
      aerobic training 1 week prior to and continuing through 8 weeks of chemotherapy
      on fatigue and functional ability in a 42-year-old newly diagnosed breast cancer
      patient. The patient participated in a supervised and home-based walking program.
      Fatigue during daily activities and functional ability (12-minute walk, ascending
      and descending stairs, sit to stand, getting to and rising from the floor, 30
      second bicep curl) were measured before and after exercise training. Results
      indicate that 5 of 7 functional measures demonstrated improvement, ranging from
      23.4- 54.5%. In addition, fatigue while performing activities of daily living, as
      well as following the performance of the functional tasks, was reduced. The
      findings of this case study indicate that fatigue can be decreased and functional
      ability can be improved as a result of aerobic training initiated 1 week before
      and continued throughout chemotherapy. This case study presents a novel approach
      to introducing exercise prior to and continued during 8 weeks of chemotherapy in
      a way that may reduce the cumulative effects of this stressor.

PMID- 17530965
TI  - Gender bias in the effects of arms and countermovement on jumping performance.
AB  - The ability to jump high is considered important in a number of sports. It is
      commonly accepted that the use of the arms and a counter movement increase jump
      height. In some sport situations (e.g., volley ball block, basketball rebound),
      athletes may not be able to utilize a counter movement or arm swing. The purpose
      of this study is to examine gender differences in the contribution of the arm
      swing and counter movement to vertical jump height. Fifty college students, 25
      men (age = 21.4 +/- 1.7 years, height = 182.2 +/- 8 cm, weight = 83.7 +/- 12.4
      kg) and 25 women (age = 20.7 +/- 1.6 years, height = 166.7 +/- 6.3 cm, weight =
      61.5 +/- 7.0 kg), performed 4 jumping movements: squat jumps with hands on hips
      (SNA), counter movement jump with hands on hips (CMNA), squat jump with arm swing
      (SA), and counter movement with arm swing (CMA). Significant differences were
      found between men's and women's performance, as well as between each type of jump
      within each gender. A mixed-model analysis of variance detected gender
      differences with respect to changes in the jumping movement. For both sexes the
      jumps in order from worst to best were SNA, CMNA, SA, and CMA. Peak power values
      for men were 4,057, 4,020, 4,644, and 4,747 W, respectively, for the 4 jumps. The
      female power values were 2,543, 2,445, 2,842, and 2,788 W, respectively, for the
      4 jumps. Arms increased jump height more than a counter movement for both
      genders, with jump heights for men at 29.6, 31, 36, and 38 cm, respectively, and
      those of women 21, 22, 26, and 27 cm, respectively. Use of the arms was found to
      increase the jump height of the men significantly more than that of women.
      Changes in jumping movements affect men and women differently. The greater
      increase in jump height for the men when using the arm swing could be because of
      greater upper body strength of men compared with women. This could have
      applications to training and upper body strength and also to modeling of jumping
      movements.

PMID- 17530966
TI  - The effects of ten weeks of lower-body unstable surface training on markers of
      athletic performance.
AB  - Initially reserved for rehabilitation programs, unstable surface training (UST)
      has recently grown in popularity in strength and conditioning and general
      exercise scenarios. Nonetheless, no studies to date have examined the effects of
      UST on performance in healthy, trained individuals. The purpose of this study was
      to determine the effects of 10 weeks of lower-body UST on performance in elite
      athletes. Nineteen healthy, trained members (ages 18-23 years) of a National
      Collegiate Athletic Association Division I collegiate men's soccer team
      participated. The experimental (US) group (n = 10) supplemented their normal
      conditioning program with lower-body exercises on inflatable rubber discs; the
      control (ST) group (n = 9) performed the same exercises on stable surfaces.
      Bounce drop jump (BDJ) and countermovement jump (CMJ) heights, 40- and 10-yard
      sprint times, and T-test (agility) times were assessed before and after the
      intervention. The ST group improved significantly on predicted power output on
      both the BDJ (3.2%) and CMJ (2.4%); no significant changes were noted in the US
      group. Both groups improved significantly on the 40- (US = -1.8%, ST = -3.9%) and
      10-yard sprint times (US = -4.0%, ST = -7.6%). The ST group improved
      significantly more than the US group in 40-yard sprint time; a trend toward
      greater improvement in the ST group was apparent on the 10-yard sprint time. Both
      groups improved significantly (US = 2.9%, ST = -4.4%) on T-test performance; no
      statistically significant changes were apparent between the groups. These results
      indicate that UST using inflatable rubber discs attenuates performance
      improvements in healthy, trained athletes. Such implements have proved valuable
      in rehabilitation, but caution should be exercised when applying UST to athletic
      performance and general exercise scenarios.

PMID- 17530967
TI  - Fatigue effects on bar kinematics during the bench press.
AB  - The bench press is one of the most popular weight training exercises. Although
      most training regimens incorporate multiple repetition sets, there are few data
      describing how the kinematics of a lift change during a set to failure. To
      examine these changes, recreational lifters (10 men and 8 women) were recruited.
      The maximum weight each subject could bench press (1RM) was determined. Subjects
      then performed as many repetitions as possible at 75% of the 1RM load. Three
      dimensional kinematic data were recorded and analyzed for all lifts. Statistical
      analysis revealed that differences between maximal and submaximal lifts and the
      kinematics of a submaximal lift change as a subject approaches failure in a set.
      The time to lift the bar more than doubled from the first to the last repetition,
      causing a decrease in both mean and peak upward velocity. Furthermore, the peak
      upward velocity occurred much earlier in the lift phase in these later
      repetitions. The path the bar followed also changed, with subjects keeping the
      bar more directly over the shoulder during the lift. In general, most of the
      kinematic variables analyzed became more similar to those of the maximal lift as
      the subjects progressed through the set, but there was considerable variation
      between subjects as to which repetition was most like the maximal lift. This
      study shows that there are definite changes in the lifting kinematics in
      recreational lifters during a set to failure and suggests it may be particularly
      important for coaches and less-skilled lifters to focus on developing the proper
      bar path, rather than reaching momentary muscular failure, in the early part of a
      training program.

PMID- 17530968
TI  - Physiological and anthropometric characteristics of young soccer players
      according to their playing position: relevance for the selection process.
AB  - The aim of this study was to establish the anthropometric and physiological
      profiles of young nonelite soccer players according to their playing position,
      and to determine their relevance for the selection process. Two hundred forty-one
      male soccer players who were members of the Getxo Arenas Club (Bizkaia)
      participated in this study. Players, age 17.31 (+/- 2.64) years, range 14-21
      years, were classified into the following groups: forwards (n = 56), midfielders
      (n = 79), defenders (n = 77), and goalkeepers (n = 29). Anthropometric variables
      of participants (height, weight, body mass index, 6 skinfolds, 4 diameters, and 3
      perimeters) were measured. Also, their somatotype and body composition (weights
      and percentages of fat, bone, and muscle) were calculated. Participants performed
      the Astrand test to estimate their absolute and relative VO2max, an endurance
      test, sprint tests (30 meters flat and 30 meters with 10 cones) and 3 jump tests
      (squat jump, counter movement jump and drop jump). Forwards were the leanest,
      presenting the highest percentage of muscle. They were the best performers in all
      the physiological tests, including endurance, velocity, agility, and power. In
      contrast, goalkeepers were found to be the tallest and the heaviest players. They
      also had the largest fat skinfolds and the highest fat percentage, but their
      aerobic capacity was the lowest. In the selection process, agility and the jump
      tests were the most discriminating for forwards. In contrast, agility, height,
      and endurance were the key factors for midfielders. The defenders group was
      characterized by a lower quantity of fat. Thus, we may conclude that
      anthropometric and physiological differences exist among soccer players who play
      in different positions. These differences fit with their different workload in a
      game. Therefore, training programs should include specific sessions for each
      positional role.

PMID- 17530969
TI  - Comparison of land- and aquatic-based plyometric training on vertical jump
      performance.
AB  - Plyometric training is a popular method by which athletes may increase power and
      explosiveness. However, plyometric training is considered a highly intense and
      potentially damaging activity particularly if practiced by the novice individual
      or if overdone. The purpose of this study was to compare vertical jump
      performance after land- and aquatic-based plyometric training. A convenience
      sample of 21 active, college-age (24 +/- 2.5 years) men were randomly assigned to
      1 of 3 groups: group I, aquatic; group II, land; and group III, control. Training
      for the AQ and LN groups consisted of a 10-minute warm-up followed by 3 sets of
      15 squat jumps, side hops, and knee-tuck jumps separated by 1-minute rests. The
      aquatic group performed the exercises in knee-level water adjusted to parallel
      the axis of the knee joint (+1 in.). The land group performed identical
      plyometric exercises on land. The control group engaged in no training.
      Participants trained twice a week for 6 weeks, and all training sessions were
      monitored. Pre- and post-test data were collected on maximum vertical jump
      height. A 2x3 analysis of variance with repeated measures was used to compare
      vertical jump height among the 3 groups. Results suggested that the aquatic- and
      land-based groups significantly (p < 0.05) outperformed the control group in the
      vertical jump. No significant difference was found in vertical jump performance
      between the aquatic- and land-based groups. It was concluded that aquatic
      training resulted in similar training effects as land-based training, with a
      possible reduction in stress due to the reduction of impact afforded by the
      buoyancy and resistance of the water upon landing.

PMID- 17530970
TI  - Concurrent endurance and explosive type strength training increases activation
      and fast force production of leg extensor muscles in endurance athletes.
AB  - The purpose of this experiment was to examine the effects of concurrent endurance
      and explosive strength training on electromyography (EMG) and force production of
      leg extensors, sport-specific rapid force production, aerobic capacity, and work
      economy in cross-country skiers. Nineteen male cross-country skiers were assigned
      to an experimental group (E, n = 8) or a control group (C, n = 11). The E group
      trained for 8 weeks with the same total training volume as C, but 27% of
      endurance training in E was replaced by explosive strength training. The skiers
      were measured at pre- and post training for concentric and isometric force-time
      parameters of leg extensors and EMG activity from the vastus lateralis (VL) and
      medialis (VM) muscles. Sport-specific rapid force production was measured by
      performing a 30-m double poling test with the maximal velocity (V(30DP)) and
      sport-specific endurance economy by constant velocity 2-km double poling test
      (CVDP) and performance (V(2K)) by 2-km maximal double poling test with roller
      skis on an indoor track. Maximal oxygen uptake (Vo(2)max) was determined during
      the maximal treadmill walking test with the poles. The early absolute forces (0
      100 ms) in the force-time curve in isometric action increased in E by 18 +/- 22%
      (p < 0.05), with concomitant increases in the average integrated EMG (IEMG) (0
      100 ms) of VL by 21 +/- 21% (p < 0.05). These individual changes in the average
      IEMG of VL correlated with the changes in early force (r = 0.86, p < 0.01) in E.
      V(30DP) increased in E (1.4 +/- 1.6%) (p < 0.05) but not in C. The V(2K)
      increased in C by 2.9 +/- 2.8% (p < 0.01) but not significantly in E (5.5 +/-
      5.8%, p < 0.1). However, the steady-state oxygen consumption in CVDP decreased in
      E by 7 +/- 6% (p < 0.05). No significant changes occurred in Vo(2)max either in E
      or in C. The present concurrent explosive strength and endurance training in
      endurance athletes produced improvements in explosive force associated with
      increased rapid activation of trained leg muscles. The training also led to more
      economical sport-specific performance. The improvements in neuromuscular
      characteristics and economy were obtained without a decrease in maximal aerobic
      capacity, although endurance training was reduced by about 20%.

PMID- 17530971
TI  - Effect of a single bout of resistance exercise on postprandial glucose and
      insulin response the next day in healthy, strength-trained men.
AB  - Postprandial blood glucose and insulin levels are both risk factors for
      developing obesity, type-2 diabetes, and coronary heart diseases. To date,
      research has shown that a single bout of moderate- to high-intensity aerobic
      exercise performed <or=24 hours before a carbohydrate ingestion has a positive
      effect on the postprandial glucose and insulin response, but the reports on the
      effect of a single bout of resistance exercise are scarce. The purpose of this
      study was to examine if a bout of resistance exercise performed 14 hours before
      ingestion of a carbohydrate-rich meal might reduce the postprandial increment in
      blood glucose and plasma insulin concentration. Ten healthy, strength-trained,
      young men participated in a meal and resistance exercise experiment. All subjects
      ingested a carbohydrate-rich meal (1 g carbohydrate per kg body weight) after
      fasting for 12 hours either with no exercise the preceding 3 days or after a bout
      of resistance exercise performed 14 hours earlier. Blood glucose and plasma
      insulin were measured every 15 and 30 minutes, respectively, for 2 hours. The
      postprandial blood glucose response measured as the peak value, the slope (from
      time 0 to peak value), and the incremental area under the curve 0-60 min (IAUC(0
      60 min)) was significantly (p <or= 0.05) reduced 14 hours after the resistance
      exercise compared with the control experiment (no exercise). However, total IAUC
      was not significantly influenced by a bout of previous resistance exercise. Also,
      the plasma insulin response did not differ between the 2 experiments. From the
      present study it would appear that a bout of resistance exercise can reduce the
      postprandial glucose elevation for at least 14 hours.

PMID- 17530972
TI  - Effects of sprint duration and exercise: rest ratio on repeated sprint
      performance and physiological responses in professional soccer players.
AB  - The purpose of this study was to examine the physiological effects of different
      sprint repetition protocols on professional footballers. Of particular interest
      were the abilities of repeated sprint protocols to induce fatigue to an extent
      observed during competitive soccer. Six professional soccer players were assessed
      for fatigue rate and physiological responses of heart rate (HR), blood lactate
      (BLa), and rating of perceived exertion (RPE) during the performance of 4
      repeated sprint drills, each totaling a sprint distance of 600 m. The 4 drills
      used 15- or 40-m sprints with 1:4 or 1:6 exercise: rest ratios. The 15-m sprint
      drill with 1:4 exercise:rest ratio induced the greatest fatigue (final sprint
      time 15% greater than initial sprint time) and greatest physiological responses.
      The 40-m sprint drill using a 1:4 exercise:rest ratio produced similar BLa and HR
      responses to the 15-m drill (13-14 mmol.L(-1) and 89% HRmax, respectively) but
      significantly lower RPE (mean +/- SD: 17.1 +/- 0.4 vs. 18.8 +/- 0.4, p < 0.05)
      and fatigue rates (11.1 vs. 15.0%, p < 0.01). Both sprint distance and
      exercise:rest ratio independently influenced fatigue rate, with the 15-m sprint
      distance and the 1:4 exercise:rest ratio inducing significantly (p < 0.01)
      greater fatigue than the 40-m sprint distance and the 1:6 exercise:rest ratio.
      The magnitude of fatigue during the 40- x 15-m sprint drill using a 1:6
      exercise:rest ratio was 7.5%, which is close to the fatigue rate previously
      reported during actual soccer play. The present study is the first to examine
      both variations in sprint distances and rest ratios simultaneously, and the
      findings may aid the design of repeated sprint training for soccer.

PMID- 17530973
TI  - Effects of proprioceptive neuromuscular facilitation stretching on stiffness and
      force-producing characteristics of the ankle in active women.
AB  - The purpose of this study was to examine the effect of proprioceptive
      neuromuscular facilitation (PNF) stretching on musculotendinous unit (MTU)
      stiffness of the ankle joint. Twenty active women were assessed for maximal ankle
      range of motion, maximal strength of planter flexors, rate of force development,
      and ankle MTU stiffness. Subjects were randomly allocated into an experimental (n
      = 10) group or control group (n = 10). The experimental group performed PNF
      stretching on the ankle joint 3 times per week for 4 weeks, with physiological
      testing performed before and after the training period. After training, the
      experimental group significantly increased ankle range of motion (7.8%), maximal
      isometric strength (26%), rate of force development (25%), and MTU stiffness
      (8.4%) (p < 0.001). Four weeks of PNF stretching contributed to an increase in
      MTU stiffness, which occurred concurrently with gains to ankle joint range of
      motion. The results confirm that MTU stiffness and joint range of motion
      measurements appear to be separate entities. The increased MTU stiffness after
      the training period is explained by adaptations to maximal isometric muscle
      contractions, which were a component of PNF stretching. Because a stiffer MTU
      system is linked with an improved the ability to store and release elastic
      energy, PNF stretching would benefit certain athletic performance due to a
      reduced contraction time or greater mechanical efficiency. The results of this
      study suggest PNF stretching is a useful modality at increasing a joint's range
      of motion and its strength.

PMID- 17530974
TI  - Effects of drop jumps added to the warm-up of elite sport athletes with a high
      capacity for explosive force development.
AB  - The purpose of this study was to evaluate the immediate influence of eccentric
      muscle action on vertical jump performance in athletes performing sports with a
      high demand of explosive force development. In this randomized, controlled
      crossover trial, 13 Swiss elite athletes (national team members in ski jump, ski
      alpine, snowboard freestyle and alpine, ski freestyle, and gymnastics) with a
      mean age of 22 years (range 20-28) were randomized into 2 groups. After a
      semistandardized warm-up, group 1 did 5 jumps from a height of 60 cm, landing
      with active stabilization in 90 degrees knee flexion. One minute after these
      modified drop jumps, they performed 3 single squat jumps (SJ) and 3 single
      countermovement jumps (CMJ) on a force platform. The athletes repeated the
      procedure after 1 hour without the modified drop jumps. In a crossover manner,
      group 2 did the first warm-up without and the second warm-up with the modified
      drop jumps. Differences of the performance (jump height and maximal power)
      between the different warm-ups were the main outcomes. The mean absolute power
      and absolute height (without drop jumps) were CMJ 54.9 W.kg(-1) (SD = 4.1), SJ
      55.0 W.kg(-1) (SD = 5.1), CMJ 44.1 cm (SD = 4.1), and SJ 40.8 cm (SD = 4.1). A
      consistent tendency for improvement with added drop jumps to the warm-up routine
      was observed compared with warm-up without drop jumps: maximal power CMJ +1.02
      W.kg(-1) (95% confidence interval [CI] = +0.03 to +2.38), p = 0.045; maximal
      power SJ +0.8 W.kg(-1) (95% CI = -0.34 to +2.02), p = 0.148; jump height CMJ
      +0.48 cm (95% CI = -0.26 to +1.2), p = 0.182; SJ +0.73 cm (95% CI = -0.36 to
      +1.18), p = 0.169. Athletes could add modified drop jumps to the warm-up before
      competitions to improve explosive force development.

PMID- 17530975
TI  - Effect of nutritionally enriched coffee consumption on aerobic and anaerobic
      exercise performance.
AB  - The purpose of this study was to compare nutritionally enriched JavaFit coffee
      (JF) to commercially available decaffeinated coffee (P) with regard to impact on
      endurance and anaerobic power performance in a physically active, college-aged
      population. Ten subjects (8 men, 2 women) performed two 30-second Wingate
      anaerobic power tests and 2 cycle ergometer tests (75% VO2 max) to exhaustion.
      Mean VO2 was measured during each endurance exercise protocol. Excess
      postexercise oxygen consumption (EPOC) and respiratory exchange ratio (RER) were
      recorded for 30 minutes following all exercise sessions. Area under the curve
      analysis was used to compare EPOC between JF and P for all exercise sessions. No
      differences were seen between JF and P in any of the power performance measures.
      However, time to exhaustion was significantly (p = 0.05) higher in JF (35.3 +/-
      15.2 minutes) compared with P (27.3 +/- 10.7 minutes). No difference between JF
      and P were seen in EPOC in either the aerobic or anaerobic exercise sessions. A
      significant (p < 0.05) difference in average 30-minute postanaerobic power
      exercise RER was seen between JF (0.87 +/- 0.04) and P (0.83 +/- 0.03), but not
      following endurance exercise. A nutritionally-enriched coffee beverage appears to
      enhance time to exhaustion during aerobic exercise, but does not provide an
      ergogenic benefit during anaerobic exercise.

PMID- 17530976
TI  - Validation of an optical encoder during free weight resistance movements and
      analysis of bench press sticking point power during fatigue.
AB  - During the concentric movement of the bench press, there is an initial high-power
      push after chest contact, immediately followed by a characteristic area of low
      power, the so-called "sticking region." During high-intensity lifting, a decline
      in power can result in a failed lift attempt. The purpose of this study was to
      determine the validity of an optical encoder to measure power and then employ
      this device to determine power changes during the initial acceleration and
      sticking region during fatiguing repeated bench press training. Twelve subjects
      performed a free weight bench press, a Smith Machine back squat, and a Smith
      Machine 40-kg bench press throw for power validation measures. All barbell
      movements were simultaneously monitored using cinematography and an optical
      encoder. Eccentric and concentric mean and peak power were calculated using time
      and position data derived from each method. Validity of power measures between
      the video (criterion) and optical encoder scores were evaluated by standard error
      of the estimate (SEE) and coefficient of variation (CV). Seven subjects then
      performed 4 sets of 6 free weight bench press repetitions progressively
      increasing from 85 to 95% of their 6 repetition maximum, with each repetition
      continually monitored by an optical encoder. The SEE for power ranged from 3.6 to
      14.4 W (CV, 1.0-3.0%; correlation, 0.97-1.00). During the free weight bench press
      training, peak power declined by approximately 55% (p < 0.01) during the initial
      acceleration phase of the final 2 repetitions of the final set. Although
      decreases in power of the sticking point were significant (p < 0.01), as early as
      repetition 5 (-40%) they reached critically low levels in the final 2 repetitions
      (>-95%). In conclusion, the optical encoder provided valid measures of kinetics
      during free weight resistance training movements. The decline in power during the
      initial acceleration phase appears a factor in a failed lift attempt at the
      sticking point.

PMID- 17530977
TI  - The application of training to failure in periodized multiple-set resistance
      exercise programs.
AB  - Few studies and reports in the body of literature have directly addressed the
      issue of whether resistance exercise sets should be performed to failure.
      Research has clearly demonstrated the superiority of performing multiple sets vs.
      single sets for increases in maximal strength. However, there is little direct
      evidence to decide conclusively whether or not multiple sets should be performed
      to failure. Therefore, the purpose of this research note was to discuss what is
      currently known concerning the application of training to failure and to
      stimulate further research on this topic. Although not essential for increases in
      muscular characteristics such as strength and hypertrophy, training to failure
      might allow advanced lifters to break through training plateaus when incorporated
      periodically into short-term microcycles. Because muscular hypertrophy is a key
      contributor to long-term increases in maximal strength, advanced lifters should
      consider training to failure occasionally. The potential mechanisms by which
      training to failure might provide an advantage are through greater activation of
      motor units and secretion of growth-promoting hormones. However, training to
      failure is not an effective stimulus without lifting at a sufficient intensity
      (percentage of 1 repetition maximum). Furthermore, training to failure should not
      be performed repeatedly over long periods, due to the high potential for
      overtraining and overuse injuries. Therefore, the training status and the goals
      of the lifter should guide the decision-making process on this issue.

PMID- 17530978
TI  - Electromyographic comparison of a stability ball crunch with a traditional
      crunch.
AB  - The purpose of this study was to compare abdominal muscle activity while
      performing a crunch on a stability ball with a traditional crunch. Forty-one
      healthy adults (23 men and 18 women) participated in the study. The subjects
      performed the crunch with the ball in 2 positions, 1 with the ball at the level
      of the inferior angles of the scapula (SB-high) and 1 with the ball at the level
      of the lower lumbar region of the back (SB-low). Surface electromyography was
      recorded from the upper and lower portions of the rectus abdominis and the
      external oblique during each repetition. Electromyography values were analyzed
      using repeated measures analyses of variance and pair-wise comparisons. Muscle
      activity for the upper and lower portions of the rectus abdominis and external
      oblique for a traditional crunch was significantly lower than for the crunch
      performed in the SB-low position but significantly greater than the SB-high
      position. Our data also showed that, on average, the abdominal muscle activity
      doubled when the stability ball was moved from the upper to the lower back
      position. These results support previous findings that a stability ball is not
      only effective for training the abdominal musculature, but, with the correct
      placement, it can also significantly increase muscle activity when compared with
      a traditional crunch. In addition, our results suggest that ball placement is
      critical for matching the appropriate overload to the condition level of the
      user.

PMID- 17530979
TI  - Cortisol and stress responses during a game and practice in female collegiate
      soccer players.
AB  - The purpose of this study was to compare the cortisol responses from a regular
      season game and a typical practice session in female National Collegiate Athletic
      Association Division I collegiate soccer players. Eighteen players were assigned
      to 2 groups, 10 starters and 8 nonstarters, depending on their playing time.
      Salivary cortisol concentration, as well as competitive sport anxiety (somatic
      and cognitive anxiety, self-confidence), was monitored before and after 1 regular
      season game and 1 typical practice session. Although salivary cortisol levels
      increased postgame for both starters (+250%) and nonstarters (+140%), they
      increased to a greater extent for the starters. Practice salivary cortisol did
      not significantly change (p > 0.05). Cognitive and somatic anxiety was greater
      pre- and postgame when compared with the pre- and postpractice scores,
      respectively. These data clearly demonstrate the psychological and physiological
      differences between soccer competition and practice in collegiate women. It
      appears that both physiological and psychological variables combine to contribute
      to the large stress hormone response to an actual competitive game.

PMID- 17530980
TI  - High-speed power training: a novel approach to resistance training in older men
      and women. A brief review and pilot study.
AB  - Over the past century, increases in both longevity and the number of older adults
      in the U.S.A. have given rise to greater numbers of functionally limited and
      disabled older adults. This has resulted in a decline in the quality of life of
      our elderly population, as well as an increased burden on our health care system.
      Resistance training (RT) with a strengthening component has traditionally been
      recommended to improve health and physical functioning in older adults. Muscle
      power (force x velocity), or the ability to produce force rapidly, has recently
      emerged as an important predictor of functioning in older men and women and has
      been the current focus of many RT studies. In this review, the physiological
      changes that contribute to the declines in muscle strength and power with aging
      will first be examined, followed by a discussion of the prevailing theories
      behind the use of traditional RT in older men and women. The rationale for high
      velocity RT will then be explored, and the recent literature on novel training
      interventions designed to improve muscle power in older adults will be discussed.
      Finally, some preliminary evidence demonstrating the benefits of high-velocity
      power training in older men and women will be presented.

PMID- 17530981
TI  - The effects of movement velocity during squatting on energy expenditure and
      substrate utilization in whole-body vibration.
AB  - The purpose of this study was to examine whether and how cycle time duration
      affects energy expenditure and substrate utilization during whole-body vibration
      (WBV). Nine men performed 3 squatting exercises in execution frequency cycles of
      6, 4, and 2 seconds to 90 degrees knee flexion with vibration (Vb+) (frequency
      was set at 30 Hz and the amplitude of vibration was 4 mm) and without vibration
      (Vb-) during 3 minutes, each with an additional load of 30% of the subject's body
      weight. A 2-way analysis of variance for VO2 revealed a significant vibration
      condition main effect (p < 0.001) and a cycle time duration effect (p < 0.001).
      When differences were analyzed by Fisher's LSD test, cycle time duration of 2
      seconds was significantly different from 4 and 6 seconds, both in Vb+ and Vb-.
      Total energy expenditure (EE(tot)), carbohydrate oxidation rate (EE(cho)), and
      fat oxidation rate (EE(fat)) demonstrated a significant vibration condition main
      effect (EE(tot): p < 0.01; EE(cho): p < 0.001; EE(fat): p < 0.001) and cycle time
      duration main effect (EE(tot) and EE(cho): p < 0.001; EE(fat): p < 0.01).
      EE(tot), EE(cho), and EE(fat) post hoc comparisons indicated that values for the
      2-second test significantly differed from 4 and 6 seconds when compared in the
      same vibration condition. VO2 and EE values were greater in Vb+ than in Vb-
      conditions with the same cycle time duration. Our study confirms that squatting
      at a greater frequency helps to maximize energy expenditure during exercise with
      or without vibration. Therefore, cycle time duration must be controlled when
      vibration exercise is prescribed.

PMID- 17530982
TI  - The influence of endurance training on multiple sprint cycling performance.
AB  - The aims of the present study were to examine the effects of endurance training
      on multiple sprint cycling performance and to evaluate the influence of recovery
      duration on the magnitude of those effects. Twenty-one physically active male
      university students were randomly assigned to either an experimental (n = 12) or
      a control (n = 9) group. The experimental group cycled for 20 minutes each day, 3
      times per week, for 6 weeks at 70% of the power output required to elicit maximal
      oxygen uptake (VO2max). Multiple sprint performance was assessed using 2 maximal
      (20 x 5 seconds) sprint cycling tests with contrasting recovery periods (10 or 30
      seconds). All tests were conducted on a friction-braked cycle ergometer. Relative
      to controls, training resulted in a 0.2 L.min(-1) increase in mean VO2max (95%
      likely range: -0.04 to 0.44 L.min(-1)). Changes in anaerobic capacity (determined
      by maximal accumulated oxygen deficit) over the same period were trivial (p =
      0.96). After training, the experimental group showed significant improvements (
      approximately 40 W), relative to controls, in multiple sprint measures of peak
      and mean power output. In contrast, training-induced reductions in fatigue were
      trivial (p = 0.63), and there were no significant between-protocol differences in
      the magnitude of any effects. In summary, 6 weeks of endurance training resulted
      in substantial improvements in multiple sprint cycling performance, the magnitude
      of the improvements being largely unaffected by the duration of the intervening
      recovery periods.

PMID- 17530983
TI  - Validation of instrumentation to monitor dynamic performance of olympic
      weightlifters.
AB  - The purpose of this study was to validate the accuracy and reliability of the
      Weightlifting Video Overlay System (WVOS) used by coaches and sport biomechanists
      at the United States Olympic Training Center. Static trials with the bar set at
      specific positions and dynamic trials of a power snatch were performed. Static
      and dynamic values obtained by the WVOS were compared with values obtained by
      tape measure and standard video kinematic analysis. Coordinate positions
      (horizontal [X] and vertical [Y]) were compared on both ends (left and right) of
      the bar. Absolute technical error of measurement between WVOS and kinematic
      values were calculated (0.97 cm [left X], 0.98 cm [right X], 0.88 cm [left Y],
      and 0.53 cm [right Y]) for the static data. Pearson correlations for all dynamic
      trials exceeded r = 0.88. The greatest discrepancies between the 2 measuring
      systems were found to occur when there was twisting of the bar during the
      performance. This error was probably due to the location on the bar where the
      coordinates were measured. The WVOS appears to provide accurate position
      information when compared with standard kinematics; however, care must be taken
      in evaluating position measurements if there is a significant amount of twisting
      in the movement. The WVOS appears to be reliable and valid within reasonable
      error limits for the determination of weightlifting movement technique.

PMID- 17530984
TI  - Whole-body vibration induced adaptation in knee extensors; consequences of
      initial strength, vibration frequency, and joint angle.
AB  - It was hypothesized that both vibration frequency and muscle length modulate the
      strengthening of muscles that is assumed to result from whole-body vibration
      (WBV). Length of knee extensor muscles during vibration is affected by the knee
      joint angle; the lengths of the knee extensors increase with more flexed knee
      joint angles. In an intervention study 28 volunteers were randomly assigned to 1
      of 4 groups. Each group received 4 weeks of WBV at 1 of 3 different frequencies
      (20, 27, or 34 Hz) or 1 of 2 different lengths of knee extensors. Voluntary,
      isometric knee extension moment-angle relationship was determined. Initially,
      stronger subjects reacted differently to WBV than weaker participants. In
      stronger subjects knee extension moment did not improve; in the weaker subjects
      considerable improvements were observed ranging from 10 to 50%. Neither vibration
      frequency nor muscle length during the intervention affected the improvements. In
      addition to strength, the knee joint angle at which the maximal joint moment was
      generated (optimal joint angle) was affected. When trained at short muscle
      lengths, optimal angle shifted to more extend joint position. WBV training at
      long muscle lengths tended to induce an opposite shift. The amount of this shift
      tended to be influenced by vibration frequency; the lower the vibration frequency
      the larger the shift. Shifts of optimal lengths occurred in both weaker and
      stronger subjects. This study shows that muscle length during training affects
      the angle of knee joint at which the maximal extension moment was generated.
      Moreover, in weaker subjects WBV resulted in higher maximal knee joint extension
      moments. Vibration frequency and muscle length during vibration did not affect
      this joint moment gain.

PMID- 17530985
TI  - 1-Set vs. 3-set resistance training: a crossover study.
AB  - This crossover study was conducted to investigate the effects of a 1-set and 3
      set strength training program. The subjects were untrained men and women who were
      randomly signed into 1 of 3 groups: 10 subjects trained during the first 9 weeks
      (training period 1) with 1 set and 8-12 repetitions per set. After the break (9
      weeks), they trained with 3 sets and 8-12 repetitions in training period 2.
      Twelve subjects started with the 3-set program and continued with the 1-set
      regime after the break. The control group (n = 7) did not train. The subjects
      were tested on 1 repetition maximum (1RM) for the biceps curl, leg press
      (unilateral: left and right), and bench press. Analysis of the data was done in a
      sampled manner for each strength training program (1-set and 3-set). The 1-set (n
      = 22) and 3-set (n = 22) programs led to significantly (p < 0.05) improved 1RM
      performances in every exercise. The relative improvements (%) for the 1RM were
      significantly higher during the 3-set program for the biceps curl and the bench
      press compared with the 1-set program. The control group exhibited no changes in
      any of the tested parameters over the course of this study. The design of this
      study allowed insight into the effects of different strength training volume
      without any genetical variations. The same subjects improved their 1RM during the
      3-set program by 2.3 kg (biceps curl; corresponding effect size = 0.24), 8.9 kg
      (leg press right; 0.30), 10.9 kg (leg press left; 0.28), and 2.5 kg (bench press;
      0.09) more than during the 1-set program. Depending on the goals of each trainee,
      these differences between the effects of different strength training volumes
      indicate that it may be worth spending more time on working out with a 3-set
      strength training regime.

PMID- 17530986
TI  - The effect of a carbohydrate and protein supplement on resistance exercise
      performance, hormonal response, and muscle damage.
AB  - The purpose of this study was to determine whether resistance exercise
      performance and postexercise muscle damage were altered when consuming a
      carbohydrate and protein beverage (CHO-PRO; 6.2% and 1.5% concentrations). Thirty
      four male subjects (age: 21.5 +/- 1.7 years; height: 177.3 +/- 1.1 cm; weight:
      77.2 +/- 2.2 kg) completed 3 sets of 8 repetitions at their 8 repetition maximum
      to volitional fatigue. The exercise order consisted of the high pull, leg curl,
      standing overhead press, leg extension, lat pull-down, leg press, and bench
      press. In a double-blind, posttest-only control group design, subjects consumed
      355 ml of either CHO-PRO or placebo (electrolyte and artificial sweetener
      beverage) 30 minutes prior to exercise, 177 ml immediately prior to exercise, 177
      ml halfway through the exercise bout, and 355 ml immediately following the
      exercise bout. There were no significant differences between groups relative to
      exercise performance. Cortisol was significantly elevated in the placebo group
      compared to the CHO-PRO group at 24 hours postexercise. Insulin was significantly
      elevated immediately pre-exercise, after the fourth lift, immediately
      postexercise, 1 hour, and 6 hours postexercise in CHO-PRO compared to the placebo
      group. Myoglobin levels in the placebo group approached significance halfway
      through the exercise bout and at 1 hour postexercise (p = 0.06 and 0.07,
      respectively) and were significantly elevated at 6 hours postexercise compared to
      the CHO-PRO group. Creatine kinase levels were significantly elevated in the
      placebo group at 24 hours postexercise compared to the CHO-PRO group. The CHO-PRO
      supplement did not improve performance during a resistance exercise bout, but
      appeared to reduce muscle damage, as evidenced by the responses of both myoglobin
      and creatine kinase. These results suggest the use of a CHO-PRO supplement during
      resistance training to reduce muscle damage and soreness.

PMID- 17530987
TI  - Influence of higher-grade walking on metabolic demands in young untrained
      Japanese women.
AB  - The primary purpose of this study was to document the physiological responses of
      level walking and running (LW/R) at various speeds, and grade walking (GW) at
      various grades on a treadmill. Twenty-four young untrained Japanese women
      performed 2 tests on the specially designed treadmill for a higher grade
      exercise. The first test was the LW/R with increase of speeds, 33.3, 66.7, 91.7,
      and 116.7 m.min(-1). The first 3 progressions were for walking and the last
      progression was for running. The second test was the GW with increase of grades
      0, 10, 20, and 30% with the velocity of 33.3 m.min(-1) in all progressions. The
      different combinations of speeds and grade for the progressions used in this
      study were selected based on the results of preliminary pilot studies, so that
      the percent heart rate maximim (%HRmax) was reached at the minimum intensities
      recommended to allow improving cardiorespiratory fitness by the American College
      of Sports Medicine (ACSM). Significant (p <or= 0.05) differences were found for
      VO2 (l.min(-1) and l.kg(-1).min(-1)), HR, %HRmax, percent heart rate reserve, and
      rating of perceived exertion between all 4 progressions in LW/R and GW. However,
      no significant differences in all variables except step rate between each
      progression for LW/R and GW. There were significant differences between measured
      VO2 and VO2 calculated from ACSM metabolic equations on all progressions in LW/R
      and GW (p <or= 0.05). These results indicated that the walking at the slower
      speed of 33.3 m.min(-1) at a higher grade of 30% is effective as much as the
      level running at 116.6 m.min(-1), and more effective than brisk level walking at
      91.7 m.min(-1) to improve cardiorespiratory fitness in untrained young women. The
      ACSM equation for walking and running underestimates VO2 for young untrained
      Japanese women. Population characteristics (e.g., body size and age) should be
      considered when designing cardiorespiratory fitness programs based on the ACSM
      equation.

PMID- 17530988
TI  - The muscle strength and size response to upper arm, unilateral resistance
      training among adults who are overweight and obese.
AB  - Overweight and obesity result in musculoskeletal impairments that limit exercise
      capacity. We examined if the muscle strength and size response to resistance
      training (RT) differed among 687 young (mean +/- SEM, 24.2 +/- 0.2 years)
      overweight and obese (OW) compared to normal weight (NW) adults as denoted by the
      body mass index (BMI). Subjects were 449 NW (22.0 +/- 0.1 kg.m(-2), 23.4 +/- 0.3
      years) and 238 OW (29.2 +/- 0.2 kg.m(-2), 25.6 +/- 0.4 years) men (n = 285) and
      women (n = 402) who underwent 12 weeks (2 d.wk(-1)) of RT of the nondominant arm.
      Maximum voluntary contraction (MVC) and 1 repetition maximum (1RM) assessed peak
      elbow flexor strength. Magnetic resonance imaging measured the biceps muscle
      cross sectional area (CSA). Multiple dependent variable analysis of covariance
      tested if muscle strength and size differed among BMI groups pre-, post-, and pre
      to-post-RT. Overweight and obese had greater MVC, 1RM, and CSA than NW pre- and
      post-RT (p < 0.001). Maximum voluntary contraction and 1RM gains were not
      different between BMI groups pre- to post-RT (p >or= 0.05). When adjusted for
      baseline values, NW had greater relative MVC (21.2 +/- 1.0 vs. 17.4 +/- 1.4%) and
      1RM (54.3 +/- 1.5 vs. 49.0 +/- 2.0%) increases than OW (p < 0.05). Normal weight
      also had greater allometric MVC (0.48 +/- 0.02 kg.kg(-0.67) vs. 0.40 +/- 0.03
      kg.kg(-0.67)) and 1RM (0.25 +/- 0.00 vs. 0.22 +/- 0.01 kg.kg(-0.67)) gains than
      OW (p < 0.05). CSA gains were greater among OW than NW (3.6 +/- 0.2 vs. 3.2 +/-
      0.1 cm(2)) (p < 0.001); however, relative CSA increases were not different
      between BMI groups (19.4 +/- 0.5 vs. 18.4 +/- 0.7%) (p >or= 0.05). Despite
      similar relative muscle size increases, relative and allometic strength gains
      were less among OW than NW. These findings indicate the short-term relative and
      allometric muscle strength response to RT may be attenuated among adults who are
      overweight and obese.

PMID- 17530989
TI  - Comparison of four different methods to measure power output during the hang
      power clean and the weighted jump squat.
AB  - Measurement of power output during resistance training is becoming ubiquitous in
      strength and conditioning programs, but there is great variation in the methods
      used. The main purposes of this study were to compare the power output values
      obtained from 4 different methods and to examine the relationships between these
      values. Male semiprofessional Australian rules football players (n = 30)
      performed hang power clean and weighted jump squat while ground reaction force
      (GRF)-time data and barbell displacement-time data were sampled simultaneously
      using a force platform and a linear position transducer attached to the barbell.
      Peak and mean power applied to the barbell was obtained from barbell displacement
      time data (method 1). Peak and mean power applied to the system (barbell +
      lifter) was obtained from 3 other methods: (a) using GRF-time data (method 2),
      (b) using barbell displacement-time data (method 3), and (c) using both barbell
      displacement-time data and GRF-time data (method 4). The peak power values (W)
      obtained from methods 1, 2, 3, and 4 were (mean +/- SD) 1,644 +/- 295, 3,079 +/-
      638, 3,821 +/- 917, and 4,017 +/- 833 in hang power clean and 1,184 +/- 115,
      3,866 +/- 451, 3,567 +/- 494, and 4,427 +/- 557 in weighted jump squat. There
      were significant differences between power output values obtained from method 1
      vs. methods 2, 3, and 4, as well as method 2 vs. methods 3 and 4. The power
      output applied to the barbell and that applied to the system was significantly
      correlated (r = 0.65-0.81). As a practical application, it is important to
      understand the characteristics of each method and consider how power output
      should be measured during the hang power clean and the weighted jump squat.

PMID- 17530990
TI  - Maximal power at different percentages of one repetition maximum: influence of
      resistance and gender.
AB  - National Collegiate Athletic Association Division I athletes were tested to
      determine the load at which maximal mechanical output is achieved. Athletes
      performed power testing at 30, 40, 50, 60, and 70% of individual 1 repetition
      maximum (1RM) in the squat jump, bench press, and hang pull exercises.
      Additionally, hang pull power testing was performed using free-form (i.e.,
      barbell) and fixed-form (i.e., Smith machine) techniques. There were differences
      between genders in optimal power output during the squat jump (30-40% of 1RM for
      men; 30-50% of 1RM for women) and bench throw (30% of 1RM for men; 30-50% of 1RM
      for women) exercises. There were no gender or form interactions during the hang
      pull exercise; maximal power output during the hang pull occurred at 30-60% of
      1RM. In conclusion, these results indicate that (a) gender differences exist in
      the load at which maximal power output occurs during the squat jump and bench
      throw; and (b) although no gender or form interactions occurred during the hang
      pull exercise, greater power could be generated during fixed-form exercise. In
      general, 30% of 1RM will elicit peak power outputs for both genders and all
      exercises used in this study, allowing this standard percentage to be used as a
      starting point in order to train maximal mechanical power output capabilities in
      these lifts in strength trained athletes.

PMID- 17530991
TI  - Identification and characterization of HIV type 1 subtypes present in the Kingdom
      of Saudi Arabia: high level of genetic diversity found.
AB  - Saudi Arabia has a very low prevalence of HIV infections and nothing is known
      about HIV strains present in the population. Here specimens were collected from
      62 HIV-1-infected patients at the King Faisal Specialist Hospital and Research
      Center, Jeddah, Saudi Arabia. Viral sequences were PCR amplified using primers
      for HIV-1 group M in gag p24, pol integrase, and env gp41 and genetic subtype was
      determined by phylogenetic analysis. HIV-1 viral sequences were amplified from 56
      of the 62 specimens. Based on phylogenetic analysis of viral sequences, subtype C
      was the most common subtype present and accounted for 39.3% of the infections
      followed by subtype G (25%), subtype B (17.9%), subtype D (3.6%), and subtypes A
      and CRF02_AG (1.8% each). In addition, for six specimens subtype classifications
      were discordant between gag, pol, and/or env; these intersubtype recombinant
      viruses account for 10.7% of the infections and consisted of recombinants of
      subtypes A/CRF01, A/CRF02, A/G, B/G, and D/CRF02. The high HIV-1 strain diversity
      suggests that there have been multiple introductions of HIV-1 into Saudi Arabia
      from several sources. Within the study population, there were five husband/wife
      pairs. For each pair, the viral sequences obtained were closely related to each
      other showing that heterosexual transmission occurred.

PMID- 17530992
TI  - Introduction of HIV type 1 into an isolated population: molecular epidemiologic
      study from Greenland.
AB  - Introduction of HIV-1 into a population may not always give rise to a subsequent
      epidemic. Greenland is an isolated and sparsely populated island in The Danish
      Kingdom. We aimed to estimate the number of introductions of HIV-1 into
      Greenland, the number of subsequent epidemics, and the countries from which the
      virus was introduced. Phylogenetic analyses were performed on three regions of
      HIV-1 (gag, pol, and env) in samples from 70 Greenlandic patients. Furthermore,
      we included gene sequences from contemporary Danish HIV-1-infected patients and
      sequences from the Los Alamos HIV Sequence Database. All Greenlandic sequences
      were subtype B except one sequence found to be a recombinant (probably CRF13).
      Sequence clusters in the phylogenetic trees indicated that there had been at
      least nine introductions of HIV-1 into Greenland. One cluster, supported by
      bootstrap values of 81, 76, and 96% for gag, pol, and env, corresponding to one
      introduction, contained 53 (76%) of the Greenland patients. The patients in the
      cluster differed from other Greenlandic patients in epidemiological parameters.
      Two distinct subgroups within the main cluster were concentrated around the two
      largest Greenlandic towns. Although HIV-1 has been introduced into Greenland at
      least nine times, only one introduction gave rise to an epidemic. The phylogeny
      did not indicate from where the main Greenland cluster had been introduced as no
      database sequence from outside Greenland was genetically close to this cluster.
      The large diversity between the main Greenland cluster and the rest of the
      sequences is most likely due to a founder effect.

PMID- 17530993
TI  - Emergence of NNRTI drug resistance mutations after single-dose nevirapine
      exposure in HIV type 1 subtype C-infected infants in India.
AB  - A feasibility study for providing single-dose nevirapine (SD-NVP) prophylaxis for
      prevention of mother-to-child transmission (PMTCT) of HIV infection provided an
      opportunity to study the emergence of nonnucleoside reverse transcriptase
      inhibitor (NNRTI) resistance mutations as a result of single-dose administration.
      The study aimed at the detection of NNRTI drug resistance mutations arising as a
      result of SD-NVP. A total of 19 and 13 samples collected at 48 h and 2 months
      postpartum, respectively, from infants that were given SD-NVP were studied for
      the presence of NNRTI drug resistance mutations by PCR amplification and
      sequencing of the HIV-1 pol gene using HIV proviral DNA. The drug resistance
      mutational analysis of final sequences was carried out using the Stanford
      University HIV Drug Resistance database (http://hivdb.stanford.edu/hiv).
      Mutations associated with NNRTI drug resistance were observed in two (10.5%) and
      six (46.15%) samples at 48 h and at 2 months, respectively. K103N, one of the
      most common mutations, was not observed in any of the samples. The emergence of
      NVP resistance must be weighed against the simplicity, efficacy, and cost
      effectiveness of SD-NVP prophylaxis in PMTCT settings in developing countries.

PMID- 17530994
TI  - The polymorphisms in DC-SIGNR affect susceptibility to HIV type 1 infection.
AB  - Dendritic cell-specific intercellular adhesion molecule-3 (ICAM-3) grabbing
      nonintegrin (DC-SIGN) and its homologue DC-SIGNR (DC-SIGN related) have been
      thought to play an important role in establishing HIV infection by enhancing
      trans-infection of CD4(+)T cells in the regional lymph nodes. To identify
      polymorphisms associated with HIV-exposed seronegative (ESN) individuals in
      Thais, genomic DNA from 102 HIV-seronegative individuals of HIV-seropositive
      spouses, 305 HIV-seropositive individuals, and 290 HIV-seronegative blood donors
      was genotyped for two single nucleotide polymorphisms (SNPs) in DC-SIGN promoter
      (-139A/G and 336A/G), a repeat number of 69 bp in Exon 4 of DC-SIGN and DC-SIGNR,
      and one SNP in Exon 5 of DC-SIGNR (rs2277998A/G). We found that the proportion of
      individuals possessing a heterozygous 7/5 and 9/5 repeat and A allele at
      rs2277998 of DC-SIGNR in HIV-seronegative individuals of HIV-seropositive spouses
      was significantly higher than HIV-seropositive individuals [p = 0.0373, OR (95%
      CI) = 0.57 (0.32,1.01); p = 0.0232, OR (95% CI) = 0.38 (0.15,0.98); and p =
      0.0445, OR (95% CI) = 0.61 (0.37,1.02), respectively]. Analysis after stratifying
      by gender showed that these associations were observed only in females but not in
      males. Moreover, HIV-seropositive females tend to have a homozygous 7/7 repeat
      more frequently than HIV-seronegative females with a marginal level of
      significance [p = 0.0556, OR (95% CI) = 1.79 (0.94,3.40)]. Haplotype analysis
      showed that the proportion of individuals possessing the 5A haplotype in HIV
      seronegative females was significantly higher than HIV-seropositive females [p =
      0.0133, OR = 0.50 (0.27,0.90)]. These associations suggest that DC-SIGNR may
      affect susceptibility to HIV infection by a mechanism that is different in
      females and males. Further studies are warranted to investigate the mechanisms of
      their function.

PMID- 17530995
TI  - Increased mortality in rural patients with HIV in New England.
AB  - Although patients with human immunodeficiency virus (HIV) infection who live in
      the rural United States receive less expert care and less antiretroviral
      treatment, the impact of living in rural areas on mortality from HIV infection is
      unstudied. We compared mortality rates in 327 rural and 317 urban patients with
      HIV infection in a retrospective cohort study using a multivariate logistic
      regression model. Rural patients with HIV infection were older at the end of
      follow-up (43.4 vs. 41.4 years, p = 0.002), and more likely white (93.0% vs.
      77.9%, p < 0.001), and a greater proportion were men who have sex with men (55.5%
      vs. 36.1%, p < 0.001). While the mean year of diagnosis was 1994 in rural
      patients and 1995 in urban patients (p < 0.001), the mean CD4(+) T cell count at
      presentation was similar in the two groups: 376 vs. 351 cells/mul (p = 0.298).
      Rural patients in our cohort were more likely to receive antiretroviral
      medications at any CD4 count (73.7 vs. 62.1%, p =0.0016), and received PCP
      prophylaxis at comparable rates (23.5% vs. 25.6%,p =0.555). Mortality was higher
      in rural patients (10.4% vs. 6.0%, p = 0.028). The risk of mortality remained
      higher in rural patients when adjusting for age, sex, race, HIV risk factors,
      year of diagnosis, travel time, lack of insurance, and receipt of antiretroviral
      treatment or PCP prophylaxis in a logistic regression model (OR 2.11, 1.064 to
      4.218, p = 0.047). Patients with HIV who live in rural areas have higher
      mortality rates than urban patients with HIV.

PMID- 17530996
TI  - Single-stranded DNA aptamer RT1t49 inhibits RT polymerase and RNase H functions
      of HIV type 1, HIV type 2, and SIVCPZ RTs.
AB  - Natural and selected resistance of HIV-1 to current anti-HIV drugs continues to
      pose serious problems to the development of HIV-1 antivirals. The viral reverse
      transcriptase (RT) is a proven therapeutic target. Single-stranded RNA and DNA
      (ssRNA and ssDNA) aptamers have been selected that specifically and potently
      inhibit RT function. In particular, the ssDNA aptamer RT1t49 was previously
      selected to recognize the RT from a subtype B strain of HIV-1 and binds with a
      reported K(d) of 4 nM. In the present work, we show that RT1t49 inhibits
      recombinant RT cloned from diverse branches of the primate lentiviral family.
      Aptamer concentrations required for half-maximal inhibition of all HIV-1, HIV-2,
      and SIV(CPZ) RTs assayed were in the low-to mid-nanomolar range for both
      polymerase and RNase H activities. Using pre-steady-state and order-of-addition
      kinetic analyses, we also established that this ssDNA aptamer competes with
      primer-template for access to RT, and that addition of a nucleoside analog RT
      inhibitor (NRTI) to the in vitro reaction enhanced the overall effectiveness of
      both drugs, while nonnucleoside analog RT inhibitors (NNRTIs) exhibited simple
      additivity. This is the first demonstration of universal inhibition of HIV and
      SIV(cpz) RTs by a nucleic acid aptamer and supports previous reports suggesting
      that resistance to RT1t49 may be exceptionally infrequent.

PMID- 17530997
TI  - Helicobacter pylori infection in symptomatic HIV-seropositive and -seronegative
      patients: a case-control study.
AB  - We conducted a case-control study in a Greek hospital to evaluate the prevalence
      and morbidity of Helicobacter pylori in HIV-infected patients. HIV-seropositive
      patients were infected by H. pylori less often than HIV-seronegative controls
      [12/58 (20.7%) versus 38/58 (65.5%),p < 0.001]. The mean CD4 count was lower for
      H. pylori-negative than H. pylori-positive HIV-infected patients (p < 0.007).
      Also, among HIV patients, prior use of antibiotics or proton pump inhibitors was
      more common in those without H. pylori infection, however, this difference was
      not statistically significant (p = 0.06). The grading of the density of H. pylori
      infection and the grading of the histomorphological findings according to the
      Sydney classification were similar between HIV-seropositive and -seronegative
      patients with H. pylori infection.

PMID- 17530998
TI  - RANTES -28G delays and DC-SIGN - 139C enhances AIDS progression in HIV type 1
      infected Japanese hemophiliacs.
AB  - The relationships between host immune factors and HIV-1 disease progression are
      still in dispute. Unlike CCR5Delta32, which has been found to delay disease
      progression of HIV-1, there still remain several factors whose effect on the
      clinical course is unconfirmed. To clarify the relationships, we selected seven
      single-nucleotide polymorphisms (SNPs) out of the previously reported factors,
      namely, RANTES promoter -28G/-403A, RANTES In1.1C, SDF-1 3'A, IL-4 promoter 
      589T, and DC-SIGN promoter -139C/-336C, and examined these in Japanese HIV-1
      infected hemophiliacs (n = 102). The genotypes were examined by the direct
      sequencing method, and the distributions of genotype and allelic frequencies were
      compared between two groups, slow progressors (n = 54) who did not develop AIDS
      more than 10 years after intravenous infection and others (progressors) (n = 48).
      The allelic frequency of RANTES -28G was significantly higher in slow progressors
      (0.185) than in the progressor group (0.074) [p = 0.023, OR = 0.35, 95% CI
      (0.142, 0.880)]. DC-SIGN promoter -139C, and appeared in progressors with
      significantly higher allelic frequency (0.333) than slow progressors [0.204, p =
      0.040, OR = 1.95, 95% CI (1.039, 3.677)]. With RANTES -403A, RANTES In1.1C, SDF-1
      3' A, IL-4 -589T, and DC-SIGN -336C, no significant difference was observed in
      allelic frequencies between the two groups. These results suggest that RANTES 
      28G was associated with delayed AIDS progression, while DC-SIGN -139C was
      associated with accelerated AIDS progression in HIV-1-infected Japanese
      hemophiliacs.

PMID- 17530999
TI  - FIV infection induces unique changes in phenotype and cellularity in the medial
      iliac lymph node and intestinal IEL.
AB  - Studies of human immunodeficiency virus-1 (HIV-1)-infected patients and simian
      immunodeficiency virus (SIV)-infected macaques have identified profound depletion
      of CD4(+) T cells and expansion of CD8(+) T cells in the gastrointestinal lamina
      propria. Less attention has been given to CD8(+) intraepithelial lymphocytes
      (IEL), and no studies have concurrently examined inductive sites such as draining
      lymph nodes. Our preliminary data in the feline immunodeficiency virus (FIV)
      animal model suggested additional changes in IEL, and marked differences in the
      responses of lymph nodes draining different mucosal sites. To address this, we
      quantified the absolute leukocyte yield and examined the phenotype of cells from
      small intestinal IEL, mesenteric lymph node (MLN), and medial iliac lymph node
      (ILN) from chronically FIV-infected cats. The cellularity of the ILN was
      increased 530% in FIV-infected animals with an expansion of CD62L(+) cells,
      suggesting an increased population of naive T cells. The number of CD4(+), as
      well as CD8(+), T cells was increased in the ILN, resulting in a CD4:CD8 ratio
      greater than 1:1. In contrast, reduced cellularity, specific loss of CD4(+) T
      cells, and inversion of the CD4:CD8 ratio was observed in the MLN, which drains
      the intestine. In IEL, loss of CD8alpha, CD8beta, and CD4-expressing T cells was
      found in FIV-infected cats. Furthermore, expression intensity of CD8alpha and
      CD5, markers known to be important in T cell function, was markedly decreased on
      IEL. These findings expand the array of immune alterations induced by lentiviral
      infection and indicate that characterization of multiple mucosal sites will be
      necessary to fully understand the pathogenesis of HIV-1 infection.

PMID- 17531000
TI  - Cell-free infectivity of HIV type 1 produced in nonpermissive cells is only
      moderately impacted by C-terminal Env truncation despite abrogation of viral
      spread.
AB  - Mutant HIV virions, encoding C-terminally truncated Env proteins, exhibit a cell
      specific replication defect, i.e., they can replicate in a few T cell lines
      (termed permissive cells) but not in the majority of T cell lines (termed
      nonpermissive cells). We have studied the properties of two mutant virions (pNL
      Tr712 and pNL-Tr752), encoding Envs with C-terminal truncations of 144 and 104
      amino acids, respectively. We show that although unable to give rise to a
      spreading infection in nonpermissive H9 cells, both cell-free pNL-Tr712 and pNL
      Tr752 virions, produced in these cells, still exhibit relatively high levels of
      infectivity (30-80% of wildtype) when tested in nonpermissive target cells.
      Compatible with this high remaining infectivity, we observed that the levels of
      Env incorporation into mutant virions, produced in nonpermissive cells, were not
      drastically reduced as has been reported by others. The high remaining
      infectivity of cell-free mutant virions in nonpermissive cells is difficult to
      reconcile with the complete lack of spreading infection in these cells. We
      demonstrate that nonpermissive cells are less susceptible to single-round
      infection with cell-free virus than permissive cells. It is thus conceivable that
      in these cells other transmission routes, e.g., cell-cell transmission, may be
      more important for total virus spread and that this route may be more severely
      impacted by the C-terminal Env truncations.

PMID- 17531001
TI  - Quantitative longitudinal analysis of T cell receptor repertoire expression in
      HIV-infected patients on antiretroviral and interleukin-2 therapy.
AB  - We have developed a single-step reverse transcriptase kinetic PCR assay (kRT-PCR)
      to accurately determine the expression of each of the 24 TCRbetaV gene families
      in CD8(+) cells. We analyzed the long-term effects of highly active
      antiretroviral therapy (HAART) on the stability of the CD8(+) T cell receptor
      (TCR) repertoire in a cohort of 15 treated and 10 untreated individuals diagnosed
      with human immunodeficiency virus (HIV) infection. The CD4(+) TCR repertoire was
      studied in a second cohort receiving interleukin-2 infusions in addition to
      HAART. Analysis was based on kinetic (quantitative) reverse-transcription PCR
      (kRT-PCR) of the TCR variable B gene (TCRbetaV). Expression of each of the 24
      Vbeta families was assessed at baseline immediately after infection and following
      initiation of HAART at 2, 4, 12, 24, and up to 192 weeks in 24-week intervals.
      Statistically significant family-specific expression changes were observed
      between treated and untreated individuals for 10 TCRbetaV families. Overall, when
      compared to untreated patients, a more stable expression of TCR genes was
      observed for HAART-treated individuals. Interestingly, this difference did not
      correlate with either CD4 or CD8 counts, which follow the expected curves for
      treated and untreated patients. When we applied our quantitative analysis to IL-2
      treated patients we observed a rapid polyclonal activation of the repertoire.
      These results suggest that homeostasis in the T cell receptor repertoire is more
      robust in those patients who stay on HAART for a long time and confirm the
      polyclonal stimulating capacity of IL-2.

PMID- 17531002
TI  - Mucosal innate immune factors in secretions from high-risk individuals immunized
      with a bivalent gp120 vaccine.
AB  - This study examined the effect of an HIV vaccine on mucosal innate factor
      expression. Serum, gingival fluid, and genital mucosal secretions were collected
      from high-risk women and men enrolled in an HIV-1 efficacy vaccine trial and from
      low-risk women and men. Samples were tested by standard ELISA for lactoferrin,
      myeloid-related protein-8/14, and secretory leukocyte protease inhibitor. No
      consistent significant changes in innate factor levels were found in serum or
      secretions from vaccinees compared to placebo recipients or from high-risk
      compared to low-risk individuals. Because of the importance of innate immunity in
      host defense, evaluation of the mucosal innate immune system should be included
      in future HIV prevention trials.

PMID- 17531003
TI  - Prevalence and genetic diversity of HIV type 1 subtypes A and D in women
      attending antenatal clinics in Uganda.
AB  - To monitor the relative prevalence and evolutionary trends of HIV-1 in Uganda, we
      conducted a retrospective study of pregnant women over the time period 1989-2000.
      From a total of 300 women sampled, we defined subtypes by heteroduplex mobility
      assay for 230 subjects and by partial sequencing and phylogenetic analyses of the
      env gene for 216 subjects. Subtypes A and D were most prevalent, and there were
      no significant trends in relative frequencies of subtypes A (45%), D (41%), C
      (5%), or recombinants (9%) over the 11 years sampled. There was also no
      phylogenetic clustering of subtypes related to geography (clinic location) or
      year of collection. Mean pairwise nucleotide diversity of subtype A (pi = 0.163)
      and subtype D (pi =0.156) samples did not differ significantly between subtypes,
      nor did these levels change over the period of the study. This report suggests
      that among pregnant women in Uganda A and D subtypes are transmitted without
      geographic constraints, and are not associated with significantly different
      transmission rates.

PMID- 17531005
TI  - Native and oxidized low-density lipoproteins modulate the vasoactive actions of
      soluble beta-amyloid peptides in rat aorta.
AB  - Cerebrovascular accumulation of Abeta (beta-amyloid) occurs in aging and AD
      (Alzheimer's disease). Hypercholesterolaemia, which is associated with raised
      plasma LDL (low-density lipoprotein), may predispose to AD. Soluble Abeta is
      found in the circulation and enhances vasoconstriction. Under conditions that may
      favour the formation of short Abeta oligomers, as opposed to more severe
      polymerization leading to Abeta fibrillogenesis, we investigated the influence of
      LDLs on the vasoactive actions of soluble Abeta. Thus the actions of Abeta40 and
      Abeta42 in combination with native or oxidized LDL on vasoconstriction to NA
      (noradrenaline) and vasodilatation to ACh (acetylcholine) were examined in rat
      aortic rings. LDL, particularly when oxidized, potentiated NA-induced
      constriction when combined with soluble Abeta40 and, especially, Abeta42. Soluble
      Abeta40 reduced relaxation induced by ACh, but Abeta42 was ineffective. Native
      and oxidized LDL also attenuated relaxation. Synergism occurred between oxidized
      LDL and Abeta with respect to ACh-induced relaxation, but not between native LDL
      and Abeta. We have shown for the first time that, under conditions that may
      result in Abeta oligomer formation, LDL, particularly when oxidized, modulates
      the vascular actions of soluble Abeta to extents greater than those reported
      previously for fibrillar Abeta preparations. Mechanisms whereby a treatable
      condition, namely hypercholesterolaemia, might contribute to the development of
      the cerebrovascular component of AD are indicated.

PMID- 17531006
TI  - Conflict of interest policy for medical journals: just a first step.

PMID- 17531007
TI  - Funding source and conflict of interest disclosures by authors and editors in
      gastroenterology specialty journals.
AB  - INTRODUCTION: Declarations of conflicts of interest have received considerable
      scrutiny in recent years. AIM: To determine if the leading gastroenterology
      journals had a formal conflict of interest disclosure policy and the extent to
      which this policy was followed by reporting of funding sources and potential
      conflicts of interests of the authors and editors of published studies. METHODS:
      We examined original articles and editorials in 12 leading journals (determined
      by impact factor) devoted to gastroenterology and hepatology. We examined the
      editorial policy of the journal (if available) on the Web site of the journal or
      in print versions of the journal and contacted the journal for further
      information on editorial policies. RESULTS: A total of 1,114 original articles
      and 154 editorials were evaluated from 12 journals. The source of funding for a
      study was disclosed in 19-99% of the articles examined with only one journal
      reporting the funding source (or absence of funding) in over 90% of articles
      studied. A potential conflict of interest was present in 0-13% of original
      articles and 0-33% of editorials. Only 2 of 12 (17%) journals publicly disclosed
      the conflicts of interest of the editors to the reader and only 3 (25%) had a
      formal method for handling editors' conflicts of interest. CONCLUSIONS: Editors
      of gastroenterology and hepatology journals have been slow to implement
      guidelines for the disclosure of their own conflicts of interest. Disclosure of
      funding sources and conflicts of interest of authors is variable despite the
      presence of conflict of interest policies at most journals.

PMID- 17531008
TI  - Postpolypectomy bleeding.

PMID- 17531009
TI  - The quest for intestinal metaplasia--is it worth the effort?
AB  - The columnar-lined esophagus (CLE) has remained an enigma for several decades.
      Starting with the basics, the definition and diagnosis of Barrett's esophagus
      (BE) continues to be a point of major debate globally leading to definitions that
      have been restrictive (requiring histologically confirmed intestinal metaplasia)
      or all-encompassing (simply the presence of CLE at endoscopy). The interest in
      intestinal metaplasia stems from studies that have consistently demonstrated
      intestinal metaplasia and dysplasia both adjacent to and remote from esophageal
      adenocarcinoma. The proponents of not requiring histology suggest that if a
      sufficient number of biopsies is obtained over an adequate period of time,
      intestinal metaplasia can usually be demonstrated in such cases and that the true
      neoplastic potential of the cardiac and fundic-type mucosa detected in the CLE
      has not been delineated. The optimal number of biopsies required to detect
      intestinal metaplasia is largely unknown, and in this issue of The American
      Journal of Gastroenterology, Harrison et al. add to the limited data on this
      subject. There is ample evidence that once a diagnosis of BE is made, it has
      significant implications on the financial, psychosocial, and insurance status of
      the patients. We feel that an optimal, practical definition of BE requires clear,
      accepted, reproducible, and clinically relevant criteria with evidence of an
      increased risk of cancer--the most crucial consequence of the lesion--and discuss
      the pros and cons of the need for documenting intestinal metaplasia in the CLE.

PMID- 17531010
TI  - Ischemic-like cholangiopathy with secondary sclerosing cholangitis in critically
      ill patients.
AB  - OBJECTIVES: Sclerosing cholangitis in critically ill patients (SC-CIP) is a newly
      described entity of severe biliary disease with progression to liver cirrhosis.
      The mechanisms leading to this form of cholangiopathy with stricture formation
      and complete obliteration of bile ducts are unknown. PATIENTS AND METHODS: In the
      last 2 yr, sclerosing cholangitis was diagnosed in 26 patients during or after
      their stay on the intensive care unit by ERCP and/or liver histology. Complete
      patient records were available for 17 patients. Histological evaluations of liver
      biopsies and of four explanted livers, parameters of cardiovascular and
      respiratory conditions, treatment modalities, and accompanying infections were
      analyzed to find further hints for the pathomechanisms leading to SC-CIP.
      RESULTS: With the beginning of cholestasis, the earliest endoscopic findings were
      intrahepatic biliary casts with impairment of the biliary flow and subsequent
      biliary infection, in most cases with Enterococcus faecium. Liver biopsy
      confirmed cholangitis and histology of explanted livers revealed ulcerated
      biliary epithelium with hemorrhagic exudates in the bile ducts. In the further
      course, progressive sclerosis with formation of multiple strictures of the bile
      ducts was observed. All patients suffered severe respiratory insufficiency with
      the need for mechanical ventilation (40.7+/-32.9 days). The PaO2/FiO2 ratio until
      beginning of cholestasis was 150.5+/-43.1. Half of the patients (9/17) were
      treated with high-frequency oscillatory ventilation and 12/17 patients by
      intermittent prone positioning. All patients required catecholamines for
      hemodynamic stabilization. CONCLUSIONS: SC-CIP is a severe and in most cases
      rapidly progressive complication of intensive care patients. Ischemic injury of
      the biliary tree with the formation of biliary casts and subsequent ongoing
      biliary infection due to multiresistant bacteria seem to be major pathogenic
      mechanisms in the development of this new entity of sclerosing cholangitis.

PMID- 17531011
TI  - Development of an experimental model of induced bacterial peritonitis in
      cirrhotic rats with or without ascites.
AB  - BACKGROUND: Spontaneous bacterial peritonitis (SBP) is a severe complication of
      cirrhotic patients associated with a high mortality. AIM: To develop an available
      experimental model of induced bacterial peritonitis in cirrhosis. MATERIAL AND
      METHODS: Sprague-Dawley rats with carbon-tetrachloride-induced cirrhosis with
      (N=22) or without (N=101) ascites were randomized to receive an intraperitoneal
      administration of different concentrations of Escherichia coli (E. coli) diluted
      in 1 mL of sterile water in ascitic rats and in different volumes in nonascitic
      rats. A subgroup of nonascitic animals received ceftriaxone 4 h after E. coli
      inoculation. Mortality of rats was evaluated 24 h after bacterial inoculation.
      RESULTS: None of the rats receiving sterile water alone and only one infected
      with 10(7) cfu of E. coli died. Ascitic rats showed a lower mortality rate than
      nonascitic rats infected with 10(8) or 10(9) cfu of E. coli (P<0.05). Mortality
      was higher with 10(9) cfu than with 10(8) cfu of E. coli in ascitic (P NS) and
      nonascitic (P<0.01) rats. A trend was noted to ward higher mortality in
      nonascitic rats inoculated with 10(8) cfu with increasing water volumes. A marked
      peritoneal polymorphonuclear cell response was observed 4 h after E. coli
      injection in both ascitic and nonascitic rats. Antibiotic therapy significantly
      reduced the mortality rate of rats infected with 10(8) cfu (P<0.01). CONCLUSIONS:
      This experimental model of induced bacterial peritonitis in cirrhosis with or
      without ascites may represent a useful tool for the study of pathogenic events
      postinfection and for the design of new therapeutic strategies to treat patients
      with SBP.

PMID- 17531012
TI  - Hepatitis C viremia increases the association with type 2 diabetes mellitus in a
      hepatitis B and C endemic area: an epidemiological link with virological
      implication.
AB  - OBJECTIVES: There is growing evidence with regard to the association between
      hepatitis C virus (HCV) infection and type 2 diabetes mellitus (T2DM). However,
      the mutual link and related virological implication have not been fully
      clarified. The impact of hepatitis B virus (HBV) infection on the epidemiological
      link remains unclear. This study aimed to elucidate the link between T2DM and
      viral hepatitis infections, especially HCV infection. It also aimed to analyze
      the associated virological characteristics and implication. METHODS: Cross
      sectional analysis of a computer-sampling survey among 10,975 participants (aged
      40-65 yr) was performed in an area endemic for HBV and HCV infections in Taiwan.
      Outcome measures included prevalence of T2DM among different groups of viral
      hepatitis infection, and comparison of related biochemical and virological
      profiles. RESULTS: Of 10,975 participants studied, 9,932 eligible participants
      were analyzed. The prevalence of T2DM, seropositivity for HBV surface antigen
      (HBsAg) and HCV antibodies (anti-HCV), and HCV viremia was 12.5%, 13.1%, 6.5%,
      and 4.8%, respectively. Prevalence of HCV viremia showed significant difference
      between T2DM and non-T2DM subjects (6.9% vs 4.5%, P<0.001), whereas anti-HCV
      seropositivity showed borderline significance (7.8% vs 6.3%, P=0.047). There was
      no HCV genotype-specific difference between HCV genotype 1 and 2 in the
      association with T2DM. On the other side, the prevalence of HBsAg (+) did not
      differ between T2DM and non-T2DM subjects (12.5% vs 13.9%, P=0.19). The
      prevalence of T2DM among HCV viremic subjects (18.0%, 86/478) was significantly
      higher than HBsAg (+) subjects (11.4%, 155/1,363, P=0.001) and those negative for
      both viral hepatitis markers (12.5%, 997/8,004, P=0.001). Multivariate logistic
      regression analyses showed that HCV viremia was the leading significant factor
      associated with T2DM, followed by male gender, hypertension, body mass index, and
      age. CONCLUSIONS: HBV infection did not increase the association with T2DM. A
      significant mutual link between T2DM and HCV viremia existed in this HBV/HCV
      endemic area. There was no HCV genotype-specific difference between HCV genotype
      1 and 2 in the association with T2DM.

PMID- 17531013
TI  - STW 5, a phytopharmacon for patients with functional dyspepsia: results of a
      multicenter, placebo-controlled double-blind study.
AB  - BACKGROUND: Functional dyspepsia (FD) constitutes a complex picture with a
      variety of epigastric symptoms. No standard therapy is currently available for
      FD. OBJECTIVE: This multicenter, placebo-controlled, double-blind study evaluated
      the efficacy and tolerability of the herbal drug STW 5, mainly comprising a fresh
      plant extract from Iberis amara. METHODS: Patients with FD were included.
      Gastrointestinal endoscopy, H. pylori-status, and a 7-day run-in phase were
      required. A total of 315 patients were treated with 3 x 20 drops/day of either
      STW 5 or placebo. Symptom assessment: day 0, 2, 4, and 8 wk of treatment. The
      principal outcome criterion was the change in a validated Gastrointestinal
      Symptom Score (GIS). Symptom severity was rated using the Likert scale. RESULTS:
      A total of 315 patients remained in the safety population. Of them, 158 were
      treated with STW 5 and 157 with placebo. The intention-to-treat population
      comprised 308 patients. Dropout number was similar in both groups. GIS showed
      improvement during the treatment period. The STW 5 group improved 6.9+/-4.8
      points up to day 56, placebo group by 5.9+/-4.3 (P<0.05). H. pylori did not
      influence the results. Drug tolerability and safety were similar in both groups.
      CONCLUSION: This placebo-controlled study with an 8-wk treatment period documents
      the efficacy of STW 5 in FD.

PMID- 17531014
TI  - Pediatric erosive esophagitis maintenance: finally, some level 1 evidence!
AB  - In children, as in adults, gastroesophageal reflux disease (GERD), particularly
      erosive esophagitis, is now believed to be a chronic disease, probably requiring
      lifelong maintenance therapy. However, this assumption has not received adequate
      clinical testing, and the provocative article by Boccia et al. in this issue of
      the Journal challenges it. The strengths of this exceptional pediatric study lie
      in its prospective, controlled, randomized character, and in its relatively long
      duration of prospective follow-up. Weaknesses of the study include its limited
      power and lack of prior validation of outcome measures. The conclusions of the
      study are applicable only to children without chronic neurologic, respiratory, or
      congenital esophageal abnormalities, the children for whom chronic proton pump
      inhibitors (PPIs) are most often required. The study's provocative results might
      be explained by the fundamental lack of GERD chronicity in otherwise healthy
      children, combined with absence of the PPI dependence that can be produced when
      PPIs are used chronically for chronic disease.

PMID- 17531015
TI  - Thoughts on the complex relationship between gastroesophageal reflux disease and
      eosinophilic esophagitis.
AB  - Recent data suggest that the interaction between gastroesophageal reflux disease
      (GERD) and eosinophilic esophagitis can be complex, and that the notion of
      establishing a clear distinction between the two disorders may be too simplistic.
      There are at least four situations in which GERD might be associated with
      esophageal eosinophils: (a) GERD causes esophageal injury that results in a mild
      eosinophilic infiltration, (b) GERD and eosinophilic esophagitis coexist but are
      unrelated, (c) eosinophilic esophagitis contributes to or causes GERD, or (d)
      GERD contributes to or causes eosinophilic esophagitis. The high frequency of
      GERD described in adult patients with eosinophilic esophagitis suggests that
      there may be more than a chance association between the two disorders. This
      report discusses potential mechanisms for the complex interaction between GERD
      and eosinophilic esophagitis. We hope that this information will serve as a
      conceptual basis for future studies on the relationship between the two
      disorders. Whereas there are a number of plausible mechanisms whereby GERD might
      contribute to the accumulation of eosinophils in the esophageal epithelium, it
      seems prudent to recommend a clinical trial of proton pump inhibitor (PPI)
      therapy even when the diagnosis of eosinophilic esophagitis seems clear-cut.
      Furthermore, we suggest that a favorable response to PPI therapy does not
      preclude a diagnosis of eosinophilic esophagitis.

PMID- 17531016
TI  - Successful treatment of common variable immunodeficiency disorder-associated
      diarrhea with budesonide: a case report.
AB  - PURPOSE: Common variable immunodeficiency disorder (CVID) is an immunological
      disease that can present with gastrointestinal (GI) symptoms including chronic
      diarrhea and abdominal pain. We report a patient with CVID and chronic diarrhea
      who significantly improved with budesonide. METHODS: A 47-yr-old woman with CVID
      associated diarrhea, steatorrhea, abdominal pain, and bloating for several years
      had an exhaustive evaluation for secondary causes of her symptoms, which was
      unrevealing. At the advice of her immunologist, she attempted a course with
      budesonide that significantly improved her GI symptoms. Given the absence of
      literature on this treatment in CVID, we attempted to systematically evaluate the
      clinical benefits after withdrawal of and retreatment with budesonide. RESULTS:
      Diarrhea, steatorrhea, abdominal pain, and bloating recurred within 2 days of
      discontinuing budesonide. All parameters assessed improved upon reinitiating
      budesonide. Further, serum immunoglobulin G (IgG) levels significantly increased
      with treatment. No significant side effects were observed with budesonide.
      CONCLUSION: This is the first report of a patient with CVID-related chronic
      diarrhea to be successfully treated with oral budesonide. This observation
      provides clinicians with an effective and safe treatment option in this difficult
      group of patients.

PMID- 17531017
TI  - Magnification or nonmagnification: that is the question.

PMID- 17531019
TI  - Tegaserod-related possible drug interactions.

PMID- 17531020
TI  - Congenital chloride diarrhea: a missed diagnosis in an adult patient.

PMID- 17531021
TI  - Capsule endoscopy and obscure gastrointestinal bleeding: are transfusion
      dependence and comorbidity further risk factors to predict a diagnosis?

PMID- 17531023
TI  - Isotretinoin and inflammatory bowel disease.

PMID- 17531024
TI  - Endoscopic management is an accepted first-line therapy for biliary complications
      after adult living donor liver transplantation.

PMID- 17531026
TI  - Primary sclerosing cholangitis and inflammatory bowel disease: where is the link?

PMID- 17531027
TI  - Successful treatment of chronic hepatitis C with pegylated interferon, ribavirin,
      and infliximab in a patient with Crohn's disease.

PMID- 17531028
TI  - Tongue hyperpigmentation in a caucasian patient coinfected with HIV and hepatitis
      C during peginterferon alfa-2b and ribavirin therapy.

PMID- 17531031
TI  - Nonsurgical approaches for the treatment of anal fissures.
AB  - Chronic anal fissure (CAF) is usually associated with internal anal sphincter
      spasm, the relief of which is central to provide fissure healing. The treatment
      for CAF has undergone a transformation in recent years from surgical to medical.
      Both the approaches share the common goal of reducing the spasm. Though surgical
      treatment has a high success rate, it can permanently impair fecal continence in
      a large number of patients. Smooth muscle relaxation seems to be a novel way by
      which more than 60% of the patients can be cured with the topical use of the
      agents. This treatment is in addition to the normalization of stools mostly.
      Smooth muscle relaxation is well tolerated, can be administered on an outpatient
      basis, does not cause any lesion of the continence organ, and subsequently, does
      not lead to any permanent latent or apparent fecal incontinence. This review
      encompasses various agents that are used for smooth muscle relaxation. In
      addition, it describes various clinical studies reported in the literature with
      their success rates and side effects.

PMID- 17531033
TI  - Africa: still the "dark continent".

PMID- 17531034
TI  - Dangers of sensationalizing conservation biology.

PMID- 17531035
TI  - Biases in legal listing under Canadian endangered species legislation.

PMID- 17531036
TI  - The value of long-term research: conservation science and practice in Tanzania.

PMID- 17531037
TI  - Long-term ecosystem dynamics in the Serengeti: lessons for conservation.
AB  - Data from long-term ecological studies further understanding of ecosystem
      dynamics and can guide evidence-based management. In a quasi-natural experiment
      we examined long-term monitoring data on different components of the Serengeti
      Mara Ecosystem to trace the effects of disturbances and thus to elucidate cause
      and-effect connections between them. The long-term data illustrated the role of
      food limitation in population regulation in mammals, particularly in migratory
      wildebeest and nonmigratory buffalo. Predation limited populations of smaller
      resident ungulates and small carnivores. Abiotic events, such as droughts and
      floods, created disturbances that affected survivorship of ungulates and birds.
      Such disturbances showed feedbacks between biotic and abiotic realms.
      Interactions between elephants and their food allowed savanna and grassland
      communities to co-occur. With increased woodland vegetation, predators' capture
      of prey increased. Anthropogenic disturbances had direct (hunting) and indirect
      (transfer of disease to wildlife) effects. Slow and rapid changes and multiple
      ecosystem states became apparent only over several decades and involved events at
      different spatial scales. Conservation efforts should accommodate both infrequent
      and unpredictable events and long-term trends. Management should plan on the time
      scale of those events and should not aim to maintain the status quo. Systems can
      be self-regulating through food availability and predator-prey interactions;
      thus, culling may not be required. Ecosystems can occur in multiple states; thus,
      there may be no a priori need to maintain one natural state. Finally,
      conservation efforts outside protected areas must distinguish between natural
      change and direct human-induced change. Protected areas can act as ecological
      baselines in which human-induced change is kept to a minimum.

PMID- 17531038
TI  - Modeling the effects of trophy selection and environmental disturbance on a
      simulated population of African lions.
AB  - Tanzania is a premier destination for trophy hunting of African lions (Panthera
      leo) and is home to the most extensive long-term study of unhunted lions. Thus,
      it provides a unique opportunity to apply data from a long-term field study to a
      conservation dilemma: How can a trophy-hunted species whose reproductive success
      is closely tied to social stability be harvested sustainably? We used an
      individually based, spatially explicit, stochastic model, parameterized with
      nearly 40 years of behavioral and demographic data on lions in the Serengeti, to
      examine the separate effects of trophy selection and environmental disturbance on
      the viability of a simulated lion population in response to annual harvesting.
      Female population size was sensitive to the harvesting of young males (> or = 3
      years), whereas hunting represented a relatively trivial threat to population
      viability when the harvest was restricted to mature males (> or = 6 years).
      Overall model performance was robust to environmental disturbance and to errors
      in age assessment based on nose coloration as an index used to age potential
      trophies. Introducing an environmental disturbance did not eliminate the capacity
      to maintain a viable breeding population when harvesting only older males, and
      initially depleted populations recovered within 15-25 years after the disturbance
      to levels comparable to hunted populations that did not experience a catastrophic
      event. These results are consistent with empirical observations of lion
      resilience to environmental stochasticity.

PMID- 17531039
TI  - Relating long-term studies to conservation practice: the case of the Serengeti
      Cheetah Project.
AB  - Although detailed, long-term scientific studies provide potentially crucial
      information for conservation, they are rare. Moreover, there is often a
      disjunction between scientists and managers that can affect whether scientific
      results are applied to help solve conservation problems. Long-term studies can
      promote increased communication between scientists and managers and hence offer
      an opportunity for constructive engagement between the two groups. We examined
      direct and indirect impacts of a 30-year study, the Serengeti Cheetah Project
      (SCP). Much of what is currently known about wild cheetahs comes from the SCP. In
      particular, the SCP has demonstrated that cheetahs have a combination of
      semisociality and ranging patterns that is unique among mammals. This system
      arises because cheetahs need to be mobile to avoid predators and competitors, yet
      maintain access to prey; this results in densities much lower than for other
      large carnivores and a requirement for large areas of heterogenous and connected
      habitat. The SCP started as a research project, but expanded into a national
      program, developing capacity for carnivore conservation within Tanzania. Long
      term studies such as the SCP are uniquely placed to establish effective working
      relationships between scientists and managers, engage local and national
      institutions, and strengthen national capacity for biodiversity conservation.
      This process is best realized through the establishment of frameworks for
      conservation that seek to align scientific research with management needs. Long
      term studies also play an important role in identifying international priorities
      for conservation. Nonetheless, the integration of science and management in
      conservation is a two-way process that requires concerted efforts by both sides
      to improve and maintain dialogue. Ultimately, conservation depends on people, and
      maintaining a commitment to a particular area over many years-such as through
      implementation of a long-term research project-helps establish mutual trust and
      respect, particularly when combined with development of local and national
      capacity for scientific research and conservation management.

PMID- 17531040
TI  - The conservation relevance of epidemiological research into carnivore viral
      diseases in the serengeti.
AB  - Recent outbreaks of rabies and canine distemper in wildlife populations of the
      Serengeti show that infectious disease constitutes a significant cause of
      mortality that can result in regional extirpation of endangered species even
      within large, well-protected areas. Nevertheless, effective management of an
      infectious disease depends critically on understanding the epidemiological
      dynamics of the causative pathogen. Pathogens with short infection cycles cannot
      persist in small populations in the absence of a more permanent reservoir of
      infection. Development of appropriate interventions requires detailed data on
      transmission pathways between reservoirs and wildlife populations of conservation
      concern. Relevant data can be derived from long-term population monitoring,
      epidemic and case-surveillance patterns, genetic analyses of rapidly evolving
      pathogens, serological surveys, and intervention studies. We examined studies of
      carnivore diseases in the Serengeti. Epidemiological research contributes to
      wildlife conservation policy in terms of management of endangered populations and
      the integration of wildlife conservation with public health interventions. Long
      term, integrative, cross-species research is essential for formulation of
      effective policy for disease control and optimization of ecosystem health.

PMID- 17531041
TI  - The contribution of long-term research at Gombe National Park to chimpanzee
      conservation.
AB  - Long-term research projects can provide important conservation benefits, not only
      through research specifically focused on conservation problems, but also from
      various incidental benefits, such as increased intensity of monitoring and
      building support for the protection of an area. At Gombe National Park, Tanzania,
      long-term research has provided at least four distinct benefits to wildlife
      conservation. (1) Jane Goodall's groundbreaking discoveries of chimpanzee (Pan
      troglodytes) tool use, hunting, and complex social relationships in what was then
      a game reserve drew attention to the area and created support for upgrading Gombe
      to national park status in 1968. (2) The highly publicized findings have earned
      Gombe and Tanzania the attention of a worldwide public that includes tourists and
      donors that provide financial support for Gombe, other parks in Tanzania, and
      chimpanzee conservation in general. (3) Crucial information on social structure
      and habitat use has been gathered that is essential for effective conservation of
      chimpanzees at Gombe and elsewhere. (4) A clear picture of Gombe's chimpanzee
      population over the past 40 years has been determined, and this has helped
      identify the greatest threats to the viability of this population, namely disease
      and habitat loss outside the park. These threats are severe and because of the
      small size of the population it is extremely vulnerable. Research at Gombe has
      led to the establishment of conservation education and development projects
      around Gombe, which are needed to build local support for the park and its
      chimpanzees, but saving these famous chimpanzees will take a larger integrated
      effort on the part of park managers, researchers, and the local community with
      financial help from international donors.

PMID- 17531042
TI  - Assessment of effectiveness of protection strategies in Tanzania based on a
      decade of survey data for large herbivores.
AB  - Considerable controversy surrounds the effectiveness of strictly protected areas
      that prohibit consumptive resource use. For Tanzania we compared temporal changes
      in densities of large herbivores among heavily protected national parks and game
      reserves, partially protected game-controlled areas, and areas with little or no
      protection. Comparisons based on surveys conducted in the late 1980s and early
      1990s versus the late 1990s and early 2000s showed three consistent patterns
      across the country. First, significant declines in the densities of large
      herbivores between these two snapshots in time overwhelmingly outnumbered
      significant increases in all protection categories. Second, more species fared
      well (increased significantly or showed no significant change) in strictly
      protected national parks than in areas with partial or no protection and in
      heavily protected game reserves relative to areas with no protection. Third,
      significantly more species fared poorly (densities declined or were too low to
      detect a decline) than fared well in areas with partial or no protection. Our
      results show that although heavy protection was generally more effective in
      maintaining large herbivore populations than partial or no protection, continued
      long-term monitoring is needed in Tanzania to inform managers whether large
      herbivores are experiencing declining population trends even within heavily
      protected areas.

PMID- 17531043
TI  - The role of research in evaluating conservation strategies in Tanzania: the case
      of the Katavi-Rukwa ecosystem.
AB  - Strict protectionism, resource extraction, protected-area community outreach,
      ecotourism, an integrated conservation and development program, comanagement
      schemes, and citizen-science initiatives are all being used to help conserve the
      remote Katavi-Rukwa ecosystem in western Tanzania. Biological and social research
      show that protectionism is successful in the conservation of large mammals but
      fails to capture diverse species communities; extractivism is appropriate for
      some resources but not for others; protected-area outreach can be effective for
      some communities; and devolved control over wildlife, in conjunction with
      ecotourism and citizen science, has considerable potential in the area. The long
      term nature of the research provides the necessary time frame to evaluate
      outcomes of different conservation strategies, uncovers dynamics within
      communities that affect attitudes and responses to conservation initiatives,
      provides impartial recommendations because changing research personnel offers
      different viewpoints, and, probably most importantly, enhances trust among
      stakeholders. Currently, there are limited institutional mechanisms for ensuring
      the input of biological and social science in shaping conservation practice in
      Tanzania, and long-term research can help informally bridge the gap.

PMID- 17531044
TI  - How broad-scale studies of patterns and processes can serve to guide conservation
      planning in Africa.
AB  - Analysis of large-scale biodiversity patterns can uncover general relationships
      and problems that need to be taken into account when conservation strategies are
      developed. Nevertheless, these large-scale patterns need to be supplemented with
      information from local studies that can identify specific problems and determine
      how the land can be divided between conservation and development interests. I
      analyzed biodiversity patterns at three different scales to show how various
      scales of research contributed to conservation planning. A gap analysis for all
      of sub-Saharan Africa revealed that the network of wildlife reserves provides
      insufficient protection of narrowly endemic and threatened species, mainly
      because such species are aggregated in certain areas with dense human
      populations. A more fine-grained analysis of the distribution of forest birds of
      eastern Africa generally confirmed the results obtained with coarse-scale data
      and added precision by identifying forest tracts where conservation actions
      should be concentrated. Detailed local distribution data for one of the
      prioritized areas, the Uluguru Mountains in Tanzania, suggest that the actions to
      halt the loss of biodiversity should be concentrated in the submontane zone,
      immediately adjacent to densely populated areas. To achieve conservation on the
      ground, these general planning tools must be supplemented with other kinds of
      research concerning land-use and local knowledge and with approaches that promote
      more sustainable development. Different types of institutions will be needed for
      these different tasks, but it is essential that researchers maintain a dialogue
      with planners in this area.

PMID- 17531045
TI  - Greenhouse gases as clues to permanence of farmlands.
AB  - Farmlands are expansive, diverse, and intensively managed ecosystems. These
      lands, so critical to human welfare, are threatened by growing stresses as demand
      for food escalates, fresh water wanes, cheap fuels deplete, and other uses jostle
      for space. With these coming pressures, how can we foster permanence on the lands
      that sustain us? In this essay I contemplate the hypothesis that the greenhouse
      gases, because they emanate from the interwoven flows of C, N, and energy in
      ecosystems, can help steer us toward permanence (sustainability). Alongside other
      indicators these emissions may detect the ecosystem's pulse, alerting us to
      inefficiencies and guiding us to better practices. To be effective signals,
      however, the greenhouse gases will need to be considered in their local settings,
      monitored longer and in more "listening places," and measured across boundaries
      of disciplines and biomes. This approach may help reduce greenhouse gas emissions
      from our farmlands. But we may find that, in the long run, the main beneficiaries
      of our inquiry have been, not just the atmosphere, but our fragile lands, perhaps
      in ways we cannot yet foresee.

PMID- 17531046
TI  - Planning for long, wide conservation corridors on private lands in the Oak Ridges
      Moraine, Ontario, Canada.
AB  - We explored the role of conservation biology in the planning of a natural
      heritage system that includes long, wide conservation corridors situated
      primarily on private lands, and established to connect natural core areas in the
      Oak Ridges Moraine of Ontario, Canada. We based our review on government
      documents, semi-structured interviews with participants involved in this land-use
      planning process, and our involvement with the issue from 1990 through 2002.
      Conservation biology had a major influence on the outcome of the land-use
      planning process for this moraine. The landform was identified as an area of
      value by the environmental movement within the context of a number of ongoing
      government studies that began in the late 1980s and early 1990s. Conservation
      biologists and planners in government, the environmental movement, and the
      private sector carried out work related to conservation biology, including
      inventories and the development and application of criteria for the delineation
      of core areas and conservation corridors. Once the political timing was favorable
      (2001-2002), decision makers linked the science of conservation biology to
      planning policies and law in Ontario. The Oak Ridges Moraine land-use planning
      process was precedent setting in Canada, and possibly internationally. To our
      knowledge this is the first time long, wide conservation corridors on private
      lands were regulated through land-use-planning legislation and led to
      restrictions on urban development and aggregate resource extraction.

PMID- 17531047
TI  - National threatened species listing based on IUCN criteria and regional
      guidelines: current status and future perspectives.
AB  - As countries worldwide become increasingly interested in conserving biodiversity,
      the profile of national threatened species lists expands and these lists become
      more influential in determining conservation priorities. The World Conservation
      Union (IUCN) Categories and Criteria for evaluating extinction risk, originally
      intended for use at the global level, are increasingly being used at the national
      level. To facilitate this process, the IUCN recently published guidelines for the
      application of the criteria at subglobal levels. We evaluated the application of
      these guidelines, focusing on the opinions and experience of the global community
      of national assessors. To assess the extent to which IUCN criteria have been used
      in official national listing efforts, we sent a survey to 180 Convention on
      Biological Diversity national focal points designated by governments. Of the
      respondents, 77% had developed national threatened species lists. Of these, 78%
      applied a version of the IUCN criteria, and 88% plan to produce future threatened
      species lists. The majority of this last group (83%) will use IUCN criteria. Of
      the countries that have or will develop a threatened species list, 82%
      incorporated their list or the IUCN criteria into national conservation
      strategies. We further explored the issues highlighted by the survey results by
      integrating the experience of assessors that have produced national lists. Most
      of the problems national assessors faced when applying the IUCN criteria arose
      when the criteria were applied at the regional level without the IUCN Regional
      Guidelines and when assessors were confused about the purpose of the IUCN
      criteria and lacked training in their proper use. To improve their clarity and
      increase their repeatability, we recommend that the IUCN increase communication
      and information exchange among countries and between regional and global
      assessors, potentially through an interactive Web site, to facilitate the
      development of national red lists and to improve their conservation value within
      and between countries.

PMID- 17531048
TI  - Population adaptive index: a new method to help measure intraspecific genetic
      diversity and prioritize populations for conservation.
AB  - In conservation biology genetic diversity is recognized as an important criterion
      to consider when prioritizing populations for protection. Today, population
      genomics offers the opportunity to evaluate both neutral and adaptive components
      of genetic diversity directly at the genome level with molecular tools. By
      screening the genome with many genetic markers, it is possible to detect loci
      supposedly under natural selection and thus of adaptive significance. We devised
      a new diversity index, the population adaptive index (PAI), which accounts for
      the adaptive value of the population it refers to. To estimate this index, we
      performed a genome scan with amplified fragment length polymorphism markers to
      identify neutral and selected loci in several populations of a widespread
      amphibian (common frog, Rana temporaria) and a threatened plant (Austrian
      dragonhead, Dracocephalum austriacum L.). We then investigated four different
      conservation strategies aimed at protecting the maximum amount of genetic
      diversity (neutral or selected). In particular we explored the relevance of the
      principle of complementarity, usually applied to the protection of species, in
      the management of intraspecific diversity. This principle advocates the
      conservation of sets of units that together maximize the species' or genetic
      diversity, which is in opposition to the traditional approach of targeting
      populations that are the most diverse individually. Four major conclusions
      emerged from these results. First, the PAI seemed to be a valuable index to
      evaluate the adaptive diversities within populations. Second, in the two species,
      the neutral and adaptive diversities within and among populations were not
      correlated, so conservation strategies based on the neutral and adaptive indexes
      would not select the same populations for protection. Third, because of its
      efficiency in conserving genetic diversity, the principle of complementarity
      deserves to be used more often for this purpose. Fourth, when neutral and
      adaptive results conflict, additional arguments (e.g., demography, ecology, and
      geographic proximity) should be considered together with levels of genetic
      diversity to determine a conservation strategy.

PMID- 17531049
TI  - Conservation easements: biodiversity protection and private use.
AB  - Conservation easements are one of the primary tools for conserving biodiversity
      on private land. Despite their increasing use, little quantitative data are
      available on what species and habitats conservation easements aim to protect, how
      much structural development they allow, or what types of land use they commonly
      permit. To address these knowledge gaps, we surveyed staff responsible for 119
      conservation easements established by the largest nonprofit easement holder, The
      Nature Conservancy, between 1985 and 2004. Most easements (80%) aimed to provide
      core habitat to protect species or communities on-site, and nearly all were
      designed to reduce development. Conservation easements also allowed for a wide
      range of private uses, which may result in additional fragmentation and habitat
      disturbance. Some residential or commercial use, new structures, or subdivision
      of the property were permitted on 85% of sampled conservation easements. Over
      half (56%) allowed some additional buildings, of which 60% restricted structure
      size or building area. Working landscape easements with ranching, forestry, or
      farming made up nearly half (46%) of the easement properties sampled and were
      more likely than easements without these uses to be designated as buffers to
      enhance biodiversity in the surrounding area. Our results demonstrate the need
      for clear restrictions on building and subdivision in easements, research on the
      compatibility of private uses on easement land, and greater public understanding
      of the trade-offs implicit in the use of conservation easements for biodiversity
      conservation.

PMID- 17531050
TI  - Establishing causes of eradication failure based on genetics: case study of ship
      rat eradication in Ste. Anne archipelago.
AB  - Determining the causes of a failed eradication of a pest species is important
      because it enables an argued adjustment of the methodologies used and the
      improvement of the protocols for future attempts. We examined how molecular
      monitoring can help distinguish between the two main reasons for an eradication
      failure (i.e., survival of some individuals vs. recolonization after
      eradication). We investigated genetic variation in seven microsatellite loci in
      ship rat (Rattus rattus) populations from four islets off the Martinique coast
      (French Caribbean). In 1999 an eradication attempt was conducted on the four
      islets. Three years later rats were observed again on two of them. We compared
      the genetic signatures of the populations before and after the eradication
      attempt. On one of the islands, the new rat population was likely a subset of the
      pre-eradication population. A weak genetic differentiation was found between
      them, with almost no new alleles observed in the new population and moderate
      F(ST) values (0.15). Moreover, assignment procedures clustered the two
      populations together. In contrast, on the other islet, many new alleles were
      observed after the eradication attempt, resulting in an increase in genetic
      diversity (from 2.57 to 3.57 mean number of alleles per locus) and strong F(ST)
      values (0.39). Moreover, genetic clustering clearly separated the two samples
      (i.e., before and after the eradication attempt) in two different populations.
      Thus, to achieve long-term eradication on these islets, it seems necessary to
      redevelop the eradication procedure to avoid individuals surviving and to prevent
      reinvasion, probably from the mainland, by installing permanent trapping and
      poisoning devices and conducting regular monitoring. We strongly encourage
      wildlife managers conducting eradication campaigns to integrate molecular
      biological tools in their protocols, which can be done easily for most common
      invasive species.

PMID- 17531051
TI  - Improving the performance of indicator groups for the identification of important
      areas for species conservation.
AB  - Indicator groups may be important tools with which to guide the selection of
      networks of areas for conservation. Nevertheless, the literature provides little
      guidance as to what makes some groups of species more suitable than others to
      guide area selection. Using distributional data on all sub-Saharan birds and
      mammals, we assessed factors that influence the effectiveness of indicator
      groups. We assessed the influence of threatened, endemic, range-restricted,
      widespread, and large-bodied species by systematically varying their number in
      indicator groups. We also assessed the influence of taxonomic diversity by
      systematically varying the number of distinct genera and families within the
      indicator groups. We selected area networks based on the indicator groups and
      tested their ability to represent a set of species, which, in terms of species
      composition, is independent of the indicator group. Increasing the proportion of
      threatened, endemic, and range-restricted species in the indicator groups
      improved effectiveness of the selected area networks; in particular it improved
      the effectiveness in representing other threatened and range-restricted species.
      In contrast increasing the proportion of widespread and large-bodied species
      decreased effectiveness. Changes in the number of genera and families only
      marginally affected the performance of indicator groups. Our results reveal that
      a focus on species of special conservation concern, which are legitimate
      conservation targets in their own right, also improves the effectiveness of
      indicator groups, in particular in representing other species of conservation
      concern.

PMID- 17531052
TI  - Functional homogenization effect of urbanization on bird communities.
AB  - We studied the community richness and dynamics of birds in landscapes recently
      affected by urbanization to test the prediction that biotic communities living in
      degraded landscapes are increasingly composed of generalist species. We analyzed
      bird communities in 657 plots monitored by the French Breeding Bird Survey from
      2001 to 2005, accounting for the probability of species detection and spatial
      autocorrelation. We used an independent land-cover program to assess urbanization
      intensity in each FBBS plot, from 1992 to 2002. We found that urbanization
      induced community homogenization and that populations of specialist species
      became increasingly unstable with increasing urbanization of the landscape. Our
      results emphasize that urbanization has a substantial impact on the spatial
      component of communities and highlight the destabilizing effect of urbanization
      on communities over time. These results illustrate that urbanization may be a
      strong driving force in functional community composition and that measuring
      community homogenization is a powerful tool in the assessment of the effects of
      landscape changes and thus aides sustainable urban planning.

PMID- 17531053
TI  - Predicting bird species distributions in reconstructed landscapes.
AB  - Landscape optimization for biodiversity requires prediction of species
      distributions under alternative revegetation scenarios. We used Bayesian model
      averaging with logistic regression to predict probabilities of occurrence for 61
      species of birds within highly fragmented box-ironbark forests of central
      Victoria, Australia. We used topographic, edaphic, and climatic variables as
      predictors so that the models could be applied to areas where vegetation has been
      cleared but may be replanted. Models were evaluated with newly acquired,
      independent data collected in large blocks of remnant native vegetation.
      Successful predictions were obtained for 18 of 45 woodland species (40%). Model
      averaging produced more accurate predictions than "single best" models. Models
      were most successful for smaller-bodied species that probably depend on
      particular vegetation types. Predictions for larger, generalist species, and
      seasonal migrants were less successful, partly because of changes in species
      distributions between model building (1995-1997) and validation (2004-2005)
      surveys. We used validated models to project occurrence probabilities for
      individual species across a 12,000-km2 region, assuming native vegetation was
      present. These predictions are intended to be used as inputs, along with
      landscape context and temporal dynamics, into optimization algorithms to
      prioritize revegetation. Longer-term data sets to accommodate temporal dynamics
      are needed to improve the predictive accuracy of models.

PMID- 17531054
TI  - Impact of forestry practices on fitness correlates and population productivity in
      an open-nesting bird species.
AB  - In the boreal forests of Fennoscandia, over 99% of forest area has been altered
      by forestry practices, which has created forest with age structures and stand
      characteristics that differ from primary forest stands. Although many researchers
      have investigated how forestry affects species abundance, few have assessed how
      forestry practices affect fitness correlates of species living in altered
      habitats, and this has negatively affected management efforts. We experimentally
      addressed the effect of standard forestry practices on fitness correlates of an
      open-nesting, long-lived bird species typical to boreal forests of Eurasia, the
      Siberian Jay (Perisoreus infaustus). We used a before-after comparison of
      reproductive data on the level of territories and found that standard forestry
      practices had a strong negative effect on the breeding success of jays. Both
      partial thinning of territories and partial clearcutting of territories reduced
      future breeding success by a factor of 0.35. Forestry practices reduced territory
      occupancy. Thus, over the 15 years of the study, productivity of the affected
      population declined over 50% as a result of territory abandonment and reduced
      breeding success. Results of previous studies on Siberian Jays suggest that the
      strong effect of forest thinning on fitness is explained by the fact that most
      common predators of nests and adults are visually oriented and thus thinning
      makes prey and nests more visible to predators. The consequences of thinning we
      observed are likely to apply to a wide range of species that rely on understory
      to provide visual protection from predators. Thus, our results are important for
      the development of effective conservation management protocols and for the
      refinement of thinning practices.

PMID- 17531055
TI  - The value of primary, secondary, and plantation forests for a neotropical
      herpetofauna.
AB  - Plantation forests and second-growth forests are becoming dominant components of
      many tropical forest landscapes. Yet there is little information available
      concerning the consequences of different forestry options for biodiversity
      conservation in the tropics. We sampled the leaf-litter herpetofauna of primary,
      secondary, and Eucalyptus plantation forests in the Jari River area of
      northeastern Brazilian Amazonia. We used four complementary sampling techniques,
      combined samples from 2 consecutive years, and collected 1739 leaf-litter
      amphibians (23 species) and 1937 lizards (30 species). We analyzed the data for
      differences among forest types regarding patterns of alpha and beta diversity,
      species-abundance distributions, and community structure. Primary rainforest
      harbored significantly more species, but supported a similar abundance of
      amphibians and lizards compared with adjacent areas of second-growth forest or
      plantations. Plantation forests were dominated by wide-ranging habitat
      generalists. Secondary forest faunas contained a number of species characteristic
      of primary forest habitat. Amphibian communities in secondary forests and
      Eucalyptus plantations formed a nested subset of primary forest species, whereas
      the species composition of the lizard community in plantations was distinct, and
      was dominated by open-area species. Although plantation forests are relatively
      impoverished, naturally regenerating forests can help mitigate some negative
      effects of deforestation for herpetofauna. Nevertheless, secondary forest does
      not provide a substitute for primary forest, and in the absence of further
      evidence from older successional stands, we caution against the optimistic claim
      that natural forest regeneration in abandoned lands will provide refuge for the
      many species that are currently threatened by deforestation.

PMID- 17531056
TI  - A resistant-kernel model of connectivity for amphibians that breed in vernal
      pools.
AB  - Pool-breeding amphibian populations operate at multiple scales, from the
      individual pool to surrounding upland habitat to clusters of pools. When
      metapopulation dynamics play a role in long-term viability, conservation efforts
      limited to the protection of individual pools or even pools with associated
      upland habitat may be ineffective over the long term if connectivity among pools
      is not maintained. Connectivity becomes especially important and difficult to
      assess in regions where suburban sprawl is rapidly increasing land development,
      road density, and traffic rates. We developed a model of connectivity among
      vernal pools for the four ambystomatid salamanders that occur in Massachusetts
      and applied it to the nearly 30,000 potential ephemeral wetlands across the
      state. The model was based on a modification of the kernel estimator (a density
      estimator commonly used in home range studies) that takes landscape resistance
      into account. The model was parameterized with empirical migration distances for
      spotted salamanders (Ambystoma maculatum), dispersal distances for marbled
      salamanders (A. opacum), and expert-derived estimates of landscape resistance.
      The model ranked vernal pools in Massachusetts by local, neighborhood, and
      regional connectivity and by an integrated measure of connectivity, both
      statewide and within ecoregions. The most functionally connected pool complexes
      occurred in southeastern and northeastern Massachusetts, areas with rapidly
      increasing suburban development. In a sensitivity analysis estimates of pool
      connectivity were relatively insensitive to uncertainty in parameter estimates,
      especially at the local and neighborhood scales. Our connectivity model could be
      used to prioritize conservation efforts for vernal-pool amphibian populations at
      broader scales than traditional pool-based approaches.

PMID- 17531057
TI  - Forecasting the expansion of zebra mussels in the United States.
AB  - Because zebra mussels spread rapidly throughout the eastern United States in the
      late 1980s and early 1990s, their spread to the western United States has been
      expected. Overland dispersal into inland lakes and reservoirs, however, has
      occurred at a much slower rate than earlier spread via connected, navigable
      waterways. We forecasted the potential western spread of zebra mussels by
      predicting the overland movement of recreational boaters with a production
      constrained gravity model. We also predicted the potential abundance of zebra
      mussels in two western reservoirs by comparing their water chemistry
      characteristics with those of water bodies with known abundances of zebra
      mussels. Most boats coming from waters infested with zebra mussels were taken to
      areas that already had zebra mussels, but a small proportion of such boats did
      travel west of the 100th meridian. If zebra mussels do establish in western U.S.
      water bodies, we predict that population densities could achieve similar levels
      to those in the Midwestern United States, where zebra mussels have caused
      considerable economic and ecological impacts. Our analyses suggest that the
      dispersal of zebra mussels to the western United States is an event of low
      probability but potentially high impact on native biodiversity and human
      infrastructure. Combining these results with economic analyses could help
      determine appropriate investment levels in prevention and control strategies.

PMID- 17531058
TI  - Threatened peripheral populations in context: geographical variation in
      population frequency and size and sexual reproduction in a clonal woody shrub.
AB  - Geographically peripheral populations of widespread species are often the focus
      of conservation because they are locally rare within political jurisdictions. Yet
      the ecology and genetics of these populations are rarely evaluated in a broader
      geographic context. Most expectations concerning the ecology and evolution of
      peripheral populations derive from the abundant-center model, which predicts that
      peripheral populations should be less frequent, smaller, less dense, and have a
      lower reproductive rate than central populations. We tested these predictions and
      in doing so evaluated the conservation value of peripheral populations for the
      clonal shrub Vaccinium stamineum L. (Ericaceae, deerberry), which is listed as
      threatened in Canada. Based on 51 populations sampled from the center to the
      northern range limits over 2 years, population frequency and size declined toward
      the range limit, but ramet density increased. Sexual reproductive output varied
      widely among populations and between years, with many populations producing very
      few seeds, but did not decline toward range margins. In fact seed mass increased
      steadily toward range limit, and this was associated with faster germination and
      seedling growth, which may be adaptive in seasonal northern environments. Our
      results did not support the prediction that clonal reproduction is more prevalent
      in peripheral populations or that it contributed antagonistically to the wide
      variation in seed production. Peripheral populations of V. stamineum are as
      productive as central populations and may be locally adapted to northern
      environments. This emphasizes the importance of a broad geographical perspective
      for evaluating the ecology, evolution, and conservation of peripheral
      populations.

PMID- 17531059
TI  - Susceptibility of common and rare plant species to the genetic consequences of
      habitat fragmentation.
AB  - Small plant populations are more prone to extinction due to the loss of genetic
      variation through random genetic drift, increased selfing, and mating among
      related individuals. To date, most researchers dealing with genetic erosion in
      fragmented plant populations have focused on threatened or rare species. We raise
      the question whether common plant species are as susceptible to habitat
      fragmentation as rare species. We conducted a formal meta-analysis of habitat
      fragmentation studies that reported both population size and population genetic
      diversity. We estimated the overall weighted mean and variance of the correlation
      coefficients among four different measures of genetic diversity and plant
      population size. We then tested whether rarity, mating system, and plant
      longevity are potential moderators of the relationship between population size
      and genetic diversity. Mean gene diversity, percent polymorphic loci, and allelic
      richness across studies were positively and highly significantly correlated with
      population size, whereas no significant relationship was found between population
      size and the inbreeding coefficient. Genetic diversity of self-compatible species
      was less affected by decreasing population size than that of obligate outcrossing
      and self-compatible but mainly outcrossing species. Longevity did not affect the
      population genetic response to fragmentation. Our most important finding,
      however, was that common species were as, or more, susceptible to the population
      genetic consequences of habitat fragmentation than rare species, even when
      historically or naturally rare species were excluded from the analysis. These
      results are dramatic in that many more plant species than previously assumed may
      be vulnerable to genetic erosion and loss of genetic diversity as a result of
      ongoing fragmentation processes. This implies that many fragmented habitats have
      become unable to support plant populations that are large enough to maintain a
      mutation-drift balance and that occupied habitat fragments have become too
      isolated to allow sufficient gene flow to enable replenishment of lost alleles.

PMID- 17531060
TI  - Genetic rescue in an isolated metapopulation of a naturally fragmented plant
      species, Parnassia palustris.
AB  - The loss of habitat of naturally fragmented species may result in isolated
      metapopulations: small groups of populations that are still connected by gene
      flow but have become isolated from other metapopulations. Genetic isolation may
      result in genetic differentiation between metapopulations and lowered genetic
      diversity within the metapopulation. Gene input from outside the metapopulation
      can hence be expected to enhance crosscompatibility and seed viability.
      Simultaneously, due to genetic drift, inbreeding, and pollen limitation in the
      small populations, fitness is likely to increase with population size within a
      metapopulation. I tested these hypotheses in three isolated metapopulations of
      the endangered plant species Parnassia palustris L. in a study area of 15 x 0.5
      km along the coast of western Belgium and northwestern France. Seed and fruit
      weight, measured in the 27 populations distributed over the three
      metapopulations, significantly differed among the metapopulations, which suggests
      genetic differentiation. These fitness variables also increased with population
      size within two metapopulations. With a pollination experiment, I investigated
      whether genetic rescue with pollen from another metapopulation enhanced seed set.
      Outside-metapopulation crosses led to a significantly higher seed set than within
      metapopulation crosses, and this effect was more pronounced in small populations.
      This means pollen from outside the metapopulation was more compatible than pollen
      from within the metapopulation, due to a lowered genetic diversity within the
      metapopulation. The seed set of naturally pollinated flowers was at least equal
      to that of hand-pollinated flowers, which can be explained by a compensation
      effect of pollen quantity and donor diversity for pollen quality. One can assume
      that the loss of genetic diversity at the level of the metapopulation affected
      loci not just related to cross compatibility. Reconnection of metapopulations by
      stepping stones may be necessary to prevent further genetic erosion and assure
      the viability of the Parnassia populations in the study area over the long term.

PMID- 17531061
TI  - Urban plants as genetic reservoirs or threats to the integrity of bushland plant
      populations.
AB  - Remnant plants in urban fringes and native plants in gardens have the potential
      to contribute to the conservation of threatened plants by increasing genetic
      diversity, effective size of populations, and levels of genetic connectedness.
      But they also pose a threat through the disruption of locally adapted gene pools.
      At Hyams Beach, New South Wales, Australia, four bushland stands of the rare
      shrub, Grevillea macleayana McGillivray, surround an urban area containing
      remnant and cultivated specimens of this species. Numbers of inflorescences per
      plant, fruits per plant, and visits by pollinators were similar for plants in
      urban gardens and bushland. Urban plants represented a substantial but complex
      genetic resource, displaying more genetic diversity than bushland plants judged
      byH(e), numbers of alleles per locus, and number of private alleles. Of 27
      private alleles in urban plants, 17 occurred in a set of 19 exotic plants.
      Excluding the exotic plants, all five stands displayed a moderate differentiation
      (F(ST)= 0.14 +/- 0.02), although the urban remnants clustered with two of the
      bushland stands. These patterns may be explained by high levels of selfing and
      inbreeding in this species and by long-distance dispersal (several seeds in the
      urban stand were fathered by plants in other stands). Genetic leakage (gene flow)
      from exotic plants to 321 seeds on surrounding remnant or bushland plants has not
      occurred. Our results demonstrate the conservation value of this group of urban
      plants, which are viable, productive, genetically diverse, and interconnected
      with bushland plants. Gene flow has apparently not yet led to genetic
      contamination of bushland populations, but high levels of inbreeding would make
      this a rare event and difficult to detect.

PMID- 17531062
TI  - Limitations of biodiversity databases: case study on seed-plant diversity in
      Tenerife, Canary Islands.
AB  - Databases on the distribution of species can be used to describe the geographic
      patterns of biodiversity. Nevertheless, they have limitations. We studied three
      of these limitations: (1) inadequacy of raw data to describe richness patterns
      due to sampling bias, (2) lack of survey effort assessment (and lack of
      exhaustiveness in compiling data about survey effort), and (3) lack of coverage
      of the geographic and environmental variations that affect the distribution of
      organisms. We used a biodiversity database (BIOTA-Canarias) to analyze richness
      data from a well-known group (seed plants) in an intensively surveyed area
      (Tenerife Island). Observed richness and survey effort were highly correlated.
      Species accumulation curves could not be used to determine survey effort because
      data digitalization was not exhaustive, so we identified well-sampled sites based
      on observed richness to sampling effort ratios. We also developed a predictive
      model based on the data from well-sampled sites and analyzed the origin of the
      geographic errors in the obtained extrapolation by means of a geographically
      constrained cross-validation. The spatial patterns of seed-plant species richness
      obtained from BIOTA-Canarias data were incomplete and biased. Therefore, some
      improvements are needed to use this database (and many others) in biodiversity
      studies. We propose a protocol that includes controls on data quality,
      improvements on data digitalization and survey design to improve data quality,
      and some alternative data analysis strategies that will provide a reliable
      picture of biodiversity patterns.

PMID- 17531063
TI  - Evaluation of Central North American prairie management based on species
      diversity, life form, and individual species metrics.
AB  - Reintroduction of fire and grazing, alone or in combination, has increasingly
      been recognized as central to the restoration of North American mixed-grass and
      tallgrass prairies. Although ecological studies of these systems are abundant,
      they have generally been observational, or if experimental, have focused on plant
      species diversity. Species diversity measures alone are not sufficient to inform
      management, which often has goals associated with life-form groups and individual
      species. We examined the effects of prescribed fire, light cattle grazing, and a
      combination of fire and grazing on three vegetation components: species
      diversity, groups of species categorized by life-form, and individual species. We
      evaluated how successful these three treatments were in achieving specific
      management goals for prairies in the Iowa Loess Hills (U.S.A.). The grazing
      treatment promoted the greatest overall species richness, whereas grazing and
      burning and grazing treatments resulted in the lowest cover by woody species.
      Burning alone best achieved the management goals of increasing the cover and
      diversity of native species and reducing exotic forb and (predominantly exotic)
      cool-season grass cover. Species-specific responses to treatments appeared
      idiosyncratic (i.e., within each treatment there existed a set of species
      attaining their highest frequency) and nearly half of uncommon species were
      present in only one treatment. Because all management goals were not achieved by
      any one treatment, we conclude that management in this region may need refining.
      We suggest that a mosaic of burning and grazing (alone and in combination) may
      provide the greatest landscape-level species richness; however, this strategy
      would also likely promote the persistence of exotic species. Our results support
      the need to consider multiple measures, including species-specific responses,
      when planning and evaluating management.

PMID- 17531064
TI  - Cultural erosion and biodiversity: canoe-making knowledge in Pohnpei, Micronesia.
AB  - Erosion of traditional knowledge and practice is a serious and accelerating
      problem, but quantitative work on traditional knowledge loss and its importance
      to biodiversity conservation is lacking. We investigated traditional knowledge of
      canoe making, a skill heavily dependent on plant biodiversity, on Pohnpei,
      Federated States of Micronesia, through a survey of 180 island residents. Our
      results showed that there has been an intergenerational erosion of canoe-making
      skills. Given current trends, the present generation of Pohnpeians may be the
      last to retain any knowledge of this traditional craft. We also identified
      several correlates of knowledge loss-including Western educational level and
      occupation-that highlight potential avenues for skill conservation via
      governments, traditional leadership, and schools. These institutions could
      intervene to emphasize traditional knowledge, which would reinforce institutional
      contexts in which traditional knowledge and practice is valued. The heightened
      awareness of the value of biodiversity that is linked to traditional knowledge is
      key to biological conservation on Pohnpei and can help support local conservation
      programs.

PMID- 17531065
TI  - Trophy hunting and conservation in Africa: problems and one potential solution.

PMID- 17531066
TI  - Hunting for consensus: reconciling bushmeat harvest, conservation, and
      development policy in West and Central Africa.

PMID- 17531075
TI  - Understanding the role of the tumour vasculature in the transport of drugs to
      solid cancer tumours.
AB  - OBJECTIVES: The vasculature of tumours imposes certain barriers that transport of
      anti-cancer drugs must overcome. Here follows an account of development of a
      general computational model that describes the mechanisms of drug transport to a
      solid tumour, with an emphasis on modelling the vasculature using solute
      transport concepts. MATERIALS AND METHODS: Investigation into the biological
      parameters that enhance/prevent anticancer drug transport to the tumour provides
      a means to evaluate the effects of these parameters on the treatment process.
      Sensitivity analysis of these provides useful insights concerning anticancer drug
      transport mechanisms from the vasculature to the solid tumour for a non-specified
      drug and non-specified solid tumour by revealing the conditions that promote or
      prevent effective drug transport. The effect of the vasculature on transport
      efficiency is studied using a parametric analysis of some of the transport and
      biological parameters. Understanding the various transport mechanisms provides a
      basis to evaluate the effectiveness of the drug treatment a priori. RESULTS: It
      was found that increases in the capillary hydrostatic pressure, diffusive
      permeability coefficient and hydraulic conductivity all result in a decrease in
      tumour size. Similarly, decreases in the interstitium hydrostatic pressure and
      filtration constant result in a decrease in tumour size. Dependence of the change
      in the tumour size to changes in these parameters is non-linear. These results
      demonstrate the potential of the integrated computational model of the tumour and
      its vasculature to estimate efficacy of a particular treatment process.
      Regardless of the dependency of the outcome on the assumed model parameters and
      the assumed kinetics, mathematical models of this type can provide more
      explanation on the issues related to the transport barriers, the efficacy of the
      treatment, and the development of effective anticancer drugs. A case study also
      is presented to demonstrate the model's flexibility to accommodate a two-cell
      glioma population.

PMID- 17531076
TI  - The influence of 3,3',5-triiodo-L-thyronine on human haematopoiesis.
AB  - OBJECTIVES: Thyroid hormones mediate many physiological and developmental
      functions in humans. The role of the 3,3',5-triiodo-L-thyronine (T3) in normal
      human haematopoiesis at the cellular and molecular levels has not been
      determined. In this study, it was revealed that the human haematopoietic system
      might be directly depended on T3 influence. MATERIALS AND METHODS: We detected
      the TRalpha1 and TRbeta1 gene expression at the mRNA level in human cord blood,
      peripheral blood and bone marrow CD34(+)-enriched progenitor cells, using the RT
      PCR method. Furthermore, we performed Western blotting to prove TRalpha1 and
      TRbeta1 expression occurs at the protein level in human cord blood, peripheral
      blood and bone marrow CD34(+) cells. In addition, the examined populations of
      cells were exposed in serum-free conditions to increasing doses of T3 and were
      subsequently investigated for clonogenic growth of granulocyte-macrophage colony
      forming unit and erythrocyte burst-forming unit in methylcellulose cultures, and
      for the level of apoptosis, by employing annexin V staining and the terminal
      deoxynucleotidyltransferase-mediated dUTP nick-end labelling method. We
      investigated expression levels of apoptosis-related Bax and antiapoptotic Bcl-2
      and Bcl-x(L) genes in the examined cells. RESULTS: We found that exposure to
      higher and lower than normal concentration of thyroid hormone significantly
      influenced clonogenecity and induced apoptosis in human haematopoietic progenitor
      cells. CONCLUSIONS: This study expands the understanding of the role of thyroid
      disorders in normal human haematopoiesis and indicates a direct influence of T3
      on this process.

PMID- 17531077
TI  - Isothiocyanate E-4IB induces MAPK activation, delayed cell cycle transition and
      apoptosis.
AB  - INTRODUCTION: Epidemiologic studies point towards a significant correlation
      between the dietary intake of isothiocyanate-containing foods and the reduced
      risk for cancer. METHODS AND RESULTS: In the current investigation, we examined
      the consequence of activating of signalling pathways during the release the cells
      from the block at G(1)/S boundary by synthetic isothiocyanate E-4IB. Using
      synchronized leukaemic HL60 cells, we show that activation of mitogen-activated
      protein kinases ERK1/2, c-Jun N-terminal kinase and p38 signalling pathways by E
      4IB are coupled with delayed transition through the cell cycle and rapid cell
      cycle arrest resulted in diminished mitochondrial membrane potential culminating
      in apoptosis. These events were accompanied by histone deacetylase inhibition,
      increase of double strand DNA breaks detected by histone H2AX phosphorylation and
      up-regulation of cell cycle regulatory protein p21 and phosphorylation of CDC25C
      phosphatase. CONCLUSION: These findings suggest that the activation of mitogen
      activated protein kinases signalling pathways, followed by the induction cell
      cycle arrest and apoptosis, might be responsible for anticancer activities of E
      4IB.

PMID- 17531078
TI  - Establishment of a tetraploid cell line from mouse H-1 (ES) cells highly
      polyploidized with demecolcine.
AB  - OBJECTIVE: Establishment of tetraploid ES cells. MATERIALS AND METHODS: Mouse H-1
      (ES) cells were polyploidized by demecolcine and released from the drug. RESULTS:
      A tetraploid cell line (4nH1 cells) was established from mouse H-1 (ES) cells
      (2nH1 cells) highly polyploidized by treatment with demecolcine. Cell cycle
      parameters of 4nH1 cells were almost the same as those of 2nH1 cells, suggesting
      that the rate of DNA synthesis was about twice that of the diploid cells. Mode of
      chromosome number of 4nH1 cells was 76, about twice that of 2nH1 cells. Cell
      volume of 4nH1 cells was about twice of that of diploid cells, indicating that
      4nH1 cells contained about twice as much total intracellular material as 2nH1
      cells. Morphology of the 4nH1 cells was flagstone-like, thus differing from that
      of the spindle-shaped 2nH1 cells, suggesting that the transformation had occurred
      during the diploid-tetraploid transition. 4nH1 cells exhibited alkaline
      phosphatase activity and formed teratocarcinomas, implying that they would be
      pluripotent. CONCLUSION: A pluripotent tetraploid cell line (4nH1 cells) was
      established.

PMID- 17531079
TI  - Mathematical model for chemotherapeutic drug efficacy in arresting tumour growth
      based on the cancer stem cell hypothesis.
AB  - OBJECTIVE: Cancer stem cells have been identified as the growth root for various
      malignant tumours and are thought to be responsible for cancer recurrence
      following treatment. MATERIALS AND METHODS: Here, a predictive mathematical model
      for the cancer stem cell hypothesis is used to understand tumour responses to
      chemotherapeutic drugs and judge the efficacy of treatments in arresting tumour
      growth. The impact of varying drug efficacies on different abnormal cell
      populations is investigated through the kinetics associated with their decline in
      response to therapy. RESULTS AND CONCLUSIONS: The model predicts the clinically
      established 'dandelion phenomenon' and suggests that the best response to
      chemotherapy occurs when a drug targets abnormal stem cells. We compare
      continuous and periodic drug infusion. For the latter, we examine the relative
      importance of the drug cell-kill rate and the mean time between successive
      therapies, to identify the key attributes for successful treatment.

PMID- 17531080
TI  - Inhibition of platelet-derived growth factor receptorbeta by imatinib mesylate
      suppresses proliferation and alters differentiation of human mesenchymal stem
      cells in vitro.
AB  - OBJECTIVES: Recent data show that Imatinib mesylate (IM) also affects
      haematopoietic stem cells (HSC), T lymphocytes and dendritic cells that do not
      harbour constitutively active tyrosine kinases. MATERIALS AND METHODS: We
      evaluated possible effects of IM on human bone marrow-derived mesenchymal stem
      cells (MSC) in vitro. RESULTS: Screening the activity of 42 receptor tyrosine
      kinases revealed an exclusive inhibition of platelet-derived growth factor
      receptorbeta (PDGFRbeta). Analysis of downstream targets of PDGFRbeta
      demonstrated IM-mediated reduction of Akt and Erk1/2 phosphorylation. Culture of
      MSC with IM led to the reversible development of perinuclear multi-vesicular
      bodies. The proliferation and clonogenicity of MSC were significantly reduced
      compared to control cultures. IM favoured adipogenic differentiation of MSC
      whereas osteogenesis was suppressed. The functional deficits described led to a
      50% reduction in the support of clonogenic haematopoietic stem cells, cultured
      for 1 month on a monolayer of MSC with IM. CONCLUSION: In summary, inhibition of
      PDGFRbeta and downstream Akt and Erk signalling by IM has a significant impact on
      proliferation and differentiation of human MSC in vitro.

PMID- 17531081
TI  - Directed engineering of umbilical cord blood stem cells to produce C-peptide and
      insulin.
AB  - OBJECTIVES: In this study, we investigated the potential of umbilical cord blood
      stem cell lineages to produce C-peptide and insulin. MATERIALS AND METHODS:
      Lineage negative, CD133+ and CD34+ cells were analyzed by flow cytometry to
      assess expression of cell division antigens. These lineages were expanded in
      culture and subjected to an established protocol to differentiate mouse embryonic
      stem cells (ESCs) toward the pancreatic phenotype. Phase contrast and
      fluorescence immunocytochemistry were used to characterize differentiation
      markers with particular emphasis on insulin and C-peptide. RESULTS: All 3
      lineages expressed SSEA-4, a marker previously reported to be restricted to the
      ESC compartment. Phase contrast microscopy showed all three lineages
      recapitulated the treatment-dependent morphological changes of ESCs as well as
      the temporally restricted expression of nestin and vimentin during
      differentiation. After engineering, each isolate contained both C-peptide and
      insulin, a result also obtained following a much shorter protocol for ESCs.
      CONCLUSIONS: Since C-peptide can only be derived from de novo synthesis and
      processing of pre-proinsulin mRNA and protein, we conclude that these results are
      the first demonstration that human umbilical cord blood-derived stem cells can be
      engineered to engage in de novo synthesis of insulin.

PMID- 17531082
TI  - A study of enamel matrix proteins on differentiation of porcine bone marrow
      stromal cells into cementoblasts.
AB  - OBJECTIVE: To further explore the role of enamel matrix proteins (EMPs) in
      periodontal regeneration, we have used porcine bone marrow-derived stromal cells
      (BMSCs) to observe whether the EMPs could have an effect on their differentiation
      into cementoblasts. MATERIALS AND METHODS: In this study, EMPs were extracted
      from porcine tooth germs by the use of acetic acid. BMSCs obtained from porcine
      iliac marrow aspiration were inoculated onto the surface of autologous root
      slices treated with or without EMPs. Following 7-day co-culture, all the BMSC
      seeded root slices, with their respective non-cell-inoculated control specimens,
      were pocketed with expanded polytetrafluoroethylene membrane and were
      transplanted subcutaneously into 11 nude mice. The animals were sacrificed after
      3 and 8 weeks, and the new specimens were processed for haematoxylin and eosin
      staining. RESULTS: Histological analysis demonstrated new cellular cementum-like
      tissue formed along EMP-treated root slices. CONCLUSION: Our work has indicated
      for the first time, differentiation of BMSCs into cementoblasts using an EMP
      based protocol.

PMID- 17531083
TI  - BubR1 deficiency results in enhanced activation of MEK and ERKs upon microtubule
      stresses.
AB  - Disruption of microtubules activates the spindle checkpoint, of which BubR1 is a
      major component. Our early studies show that BubR1 haplo-insufficiency results in
      enhanced mitotic slippage in vitro and tumorigenesis in vivo. OBJECTIVE: Given
      that both MAPKs/ERKs and MEK play an important role during mitosis, we
      investigated whether there existed regulatory relationship between the MAPK
      signalling pathway and BubR1. METHOD AND RESULTS: Here, we have demonstrated that
      BubR1 deficiency is correlated with enhanced activation of MEK and ERKs after
      disruption of microtubule dynamics. Specifically, treatment with nocodazole and
      paclitaxel resulted in hyper-activation of ERKs and MEK in BubR1(+/-) murine
      embryonic fibroblasts (MEF) compared to that of wild-type MEFs. This enhanced
      activation of ERKs and MEK was at least partly responsible for more successful
      proliferation completion when cells were treated with nocodazole. BubR1 knockdown
      via RNAi resulted in enhanced activation of ERKs and MEK in HeLa cells,
      correlating with inhibition of PP1, a negative regulator of MEK. Moreover, when
      BubR1 was partially inactivated due to premature missegregation of chromosomes
      after Sgo1 depletion, phosphorylation of ERKs and MEK was enhanced in mitotic
      cells; in contrast, little, if any activated ERKs and MEK were detected in
      mitotic cells induced by nocodazole. Furthermore, BubR1, activated ERKs and
      activated MEK all localized to spindle poles during mitosis, and also, the
      proteins physically interacted with each other. CONCLUSION: Our studies suggest
      that there exists a cross-talk between spindle checkpoint components and ERKs and
      MEK and that BubR1 may play an important role in mediating the cross-talk.

PMID- 17531084
TI  - Deletion of a single allele of Cx43 is associated with a reduction in the gap
      junctional intercellular communication and increased cell proliferation of mouse
      lung pneumocytes type II.
AB  - OBJECTIVES: Connexins (Cx) are proteins that form the gap junctional channels at
      neighbouring plasma membranes between adjacent cells. Cxs are involved in cell
      communication, which is reportedly correlated with cell proliferation and
      differentiation. Alterations in connexin expression and/or gap junctional
      intercellular communication (GJIC) capacity have long been postulated to be
      important in a number of pathological conditions including cancer. This study was
      performed to determine the consequences of the deletion of a single allele of
      Gja1 (Cx43 gene) in Alveolar Type II cells (APTIIs), and its impact on GJIC and
      cell proliferation. MATERIAL AND METHODS: In order to do so, APTIIs from wild
      type (Cx43(+/+)) and heterozygous (Cx43(+/-)) mice were harvested and cultured
      for 4 days. The GJIC capacity was evaluated by scrape-loading method, with the
      transfer of lucifer yellow dye. The expression of Cx43 was evaluated by
      immunofluorescence method and Western blotting. Cell proliferation was evaluated
      by 3-(4,5-dimethylthazol-2-yl)-2,5-diphenyltetrazolium bromide assay. RESULTS: It
      was observed that GJIC capacity was significantly reduced and cell proliferation
      index was significantly higher in Cx43(+/-) cells compared to Cx43(+/+) cells.
      CONCLUSIONS: These results show that knocking out one allele of Cx43 leads to a
      lower cell to cell communication capacity, and consequently induces a higher cell
      proliferation. Because chemically induced lung adenomas in mice are known to
      originate from APTIIs, these alterations may play a critical role in their
      susceptibility to lung carcinogenesis.

PMID- 17531085
TI  - Chromophore-assisted light inactivation of pKi-67 leads to inhibition of
      ribosomal RNA synthesis.
AB  - OBJECTIVES: Expression of the nuclear Ki-67 protein (pKi-67) is strongly
      associated with cell proliferation. For this reason, antibodies against this
      protein are widely used as prognostic tools for the assessment of cell
      proliferation in biopsies from cancer patients. Despite this broad application in
      histopathology, functional evidence for the physiological role of pKi-67 is still
      missing. Recently, we proposed a function of pKi-67 in the early steps of
      ribosomal RNA (rRNA) synthesis. Here, we have examined the involvement of pKi-67
      in this process by photochemical inhibition using chromophore-assisted light
      inactivation (CALI). MATERIALS AND METHODS: Anti-pKi-67 antibodies were labelled
      with the fluorochrome fluorescein 5(6)-isothiocyanate and were irradiated after
      binding to their target protein. RESULTS: Performing CALI in vitro on cell
      lysates led to specific cross-linking of pKi-67. Moreover, the upstream binding
      factor (UBF) necessary for rRNA transcription was also partly subjected to cross
      link formation, indicating a close spatial proximity of UBF and pKi-67. CALI in
      living cells, using micro-injected antibody, caused a striking relocalization of
      UBF from foci within the nucleoli to spots located at the nucleolar rim or within
      the nucleoplasm. pKi-67-CALI resulted in dramatic inhibition of RNA polymerase I
      dependent nucleolar rRNA synthesis, whereas RNA polymerase II-dependent
      nucleoplasmic RNA synthesis remained almost unaltered. CONCLUSIONS: Our data
      presented here argue for a crucial role of pKi-67 in RNA polymerase I-dependent
      nucleolar rRNA synthesis.

PMID- 17531086
TI  - Role of c-Fos/JunD in protecting stress-induced cell death.
AB  - OBJECTIVE: The exposure of mammalian cells to extracellular stress induces the
      expression of immediate early genes such as c-fos and c-jun and activates
      transcription factor activator protein-1 (AP-1). The purpose of the current study
      was to investigate the role of c-Fos and JunD in stress-induced cell death.
      MATERIALS AND METHODS: We exposed cultured primary mouse embryonic fibroblasts
      (MEF) to ultraviolet light (UV-C) or hydrogen peroxide (H(2)O(2)). Induction of c
      Fos and JunD and activation of MAPK/ERK1/2 signalling in the presence or absence
      of a MAPK inhibitor were analyzed by western blotting. Activation of AP-1
      transcription factors was detected by the electrophoretic mobility shift assay
      and immunoprecipitation. Cell death was measured by changes in caspase 3
      activities and nuclear morphology. Effects of c-Fos and JunD expression on cell
      death were investigated by transfection. RESULTS: We found that the exposure of
      cultured primary MEF cells to UV or H(2)O(2) caused a significant increase in c
      Fos and JunD protein levels. In addition, these two proteins formed complexes
      with each other and contributed to activation of AP-1 transcription complexes.
      More importantly, under both stress conditions, overexpression of JunD alone or
      overexpression of both c-Fos and JunD reduced caspase 3 activity and cell death.
      At the same time, UV irradiation activated the MAPK/ERK1/2 signalling pathway.
      The suppression of MEK1/ERK1/2 activation inhibited UV-induced expression of c
      Fos and JunD and increased caspase 3 activity and cell death. CONCLUSION: Our
      results suggest that both UV and H(2)O(2 )induce the activation of c-Fos/JunD AP
      1 complexes resulting in the prevention of cell death. Moreover, UV irradiation
      induced increases in c-Fos/JunD expression in primary MEF cells are mediated
      through the activation of the MAPK/ERK1/2 signalling pathway.

PMID- 17531087
TI  - Cooperation between Wnt and Notch signalling in human breast cancer.
AB  - The Wnt and Notch signalling pathways play major roles in mammary gland
      development and tumourigenesis. During development, these pathways have opposing
      effects. However, in a recent paper Ayyanan and coworkers show that expression of
      Wnt1 is sufficient to transform primary human mammary epithelial cells, and that
      this is in part due to activation of the Notch pathway. This indicates that
      during tumourigenesis the two pathways cooperate. Here we ask why activation of
      Wnt signalling alone is sufficient to cause transformation; whether there is
      evidence for inhibitory crosstalk between the pathways during tumourigenesis; and
      whether cooperation between these pathways occurs in other forms of cancer.

PMID- 17531088
TI  - Pharmacokinetics and pharmacodynamics of fosmidomycin monotherapy and combination
      therapy with clindamycin in the treatment of multidrug resistant falciparum
      malaria.
AB  - BACKGROUND: The study investigated the pharmacokinetics of fosmidomycin when
      given alone and in combination with clindamycin in patients with acute
      uncomplicated falciparum malaria. METHODS: A total of 15 and 18 patients with
      acute uncomplicated Plasmodium falciparum malaria who fulfilled the enrollment
      criteria were recruited from out-patient department of Mae Sot Hospital, Tak
      Province, Thailand. Patients were treated with monotherapy with fosmidomycin at
      the dose of 1,200 mg every 8 hours for 7 days (n = 15) or combination therapy
      with fosmidomycin (900 mg every 12 hours for 7 days) and clindamycin (600 mg
      every 12 hours for 7 days) (n = 18). Blood samples were taken for pharmacokinetic
      investigations of clindamycin and/or fosmidomycin and 24-hour urine samples were
      collected during dosing period. Efficacy assessments included clinical and
      parasitological evaluation. Safety and tolerability were assessed based on
      clinical and laboratory investigations. RESULTS: Both mono- and combination
      therapy regimens of fosmidomycin were well tolerated with no serious adverse
      events. Combination therapy with fosmidomycin and clindamycin was proven highly
      effective with 100% cure rate, whereas cure rate of monotherapy was 22% (28-day
      follow up). Pharmacokientics of fosmidomycin following mono- and combination
      therapy were similar except Vz/F and CL/F, which were significantly smaller in
      the combination regimen. Plasma concentration-time profiles of both fosmidomycin
      and clindamycin were best fit with a one-compartment open model with first-order
      absorption and elimination and with absorption lag time. Steady-state plasma
      concentrations of fosmidomycin and clindamycin were attained at about the second
      or third dose. There was no evidence of dose accumulation during multiple dosing.
      Urinary recovery of fosmidomycin was 18.7 and 20% following mono- and combination
      therapy, respectively. CONCLUSION: Pharmacokinetic dose optimization of
      fosmidomycin-clindamycin combination therapy with the course of treatment of not
      longer than three days is required to obtain a regimen which is safe and produced
      100% cure for multidrug-resistant P. falciparum.

PMID- 17531089
TI  - Absidia Corymbifera in an immune competent accident victim with multiple
      abdominal injuries: case report.
AB  - BACKGROUND: We report a case of mucormycosis in a healthy 17-year-old accident
      victim with multiple abdominal injuries which was caused by infection with
      Absidia Corymbifera, a ubiquitous saphrophyte in the ground. CASE PRESENTATION:
      The patient was admitted to hospital with massive abdominal trauma. During an 8
      hour emergency operation he received transfusions of compacted red blood cells,
      plasma, platelets and hemagel. He developed a crush syndrome with acute renal
      failure, resolved with extra-corporeal dialysis and had to undergo splenectomy
      because of spleen hematoma. As wound secretion and central venous catheter (CVC)
      blood cultures and drainage fluid were positive for Enterococcus Faecium,
      Providentia Rettgeri, Hafnia Alvei and Candida Albicans, tecoplanin,
      metronidazole, imipenem, and flucanozole were administered. Although the CVC was
      changed high fever persisted and discharge continued from the large abdominal
      wound. Repeated tampons in different sections and wound secretion smears were
      positive for A. corymbifera. Flucanozole was stopped and liposomal amphotericin
      (Ambisome; 5 mg/Kg i.v.) given for over 3 months. The patient improved; fever
      gradually disappeared. After 8 days, tampons and wound secretion smears were
      negative for A. corymbifera. No other fungal infections developed. Drainage fluid
      was later positive for tecoplanin-resistant E. faecium and Pseudomonas Aeroginosa
      responding only to meropenem and ciprofloxacin. Abdominal computerized tomography
      visualized fluid accumulation around the iliac-femoral bypass. Abcess was ruled
      out when scintigraphy showed no tracer uptake. The lesion was drained. Drainage
      fluid cultures were negative for bacteria and fungi. Fluid accumulation gradually
      disappeared with prolonged antibiotic and antifungal therapy. One year after the
      accident the patient is in good health, with normal quality of life. CONCLUSION:
      Successful outcome was due to early, specific antifungal therapy, at sufficiently
      high dosage which was prolonged for an adequate period of time. Early diagnosis
      of mucormycosis is essential for efficacious anti-fungal treatment and prevention
      of irreversible spread of mucormycosis to vital organs. It presupposes awareness
      that A. corymbifera infection can develop in healthy individuals who are stressed
      and traumatized through skin-ground contact in accidents.

PMID- 17531090
TI  - Clopidogrel in Orthopaedic patients: a review of current practice in Scotland.
AB  - BACKGROUND: Clopidogrel bisulfate is an antiplatelet agent used to prevent
      ischaemic events in patients with vascular disease. Current guidelines recommend
      withholding clopidogrel for 7 days pre-operatively. However these are not based
      on orthopaedic patients. We therefore decided to survey current orthopaedic
      practice to see whether this complied with available clinical data. METHOD: A
      questionnaire was sent to all orthopaedic consultants in Scotland. Four
      haematology departments, and the manufacturers, were contacted to ask for their
      recommendations, and a database search was performed. RESULTS: 140 questionnaires
      were sent with a 60.7% response. 84.7% of respondents have encountered patients
      on clopidogrel. Of those, 13.9% did not routinely stop it, and 86.1% stopped it 5
      21 days pre-operatively (47.2% at 7 days).45.9% had a unit policy on stopping
      clopidogrel, and the majority (69.4%) did not consult their haematology
      department prior to instituting their policy.Increased peri-operative bleeding
      was the most reported complication (22.6%). However this was only noted in those
      who stopped clopidogrel greater-than 7 days pre-operatively. Haematology advice
      ranged from continuing clopidogrel peri-operatively to stopping it 7 days pre
      operatively and starting low-molecular-weight-heparin for thrombo-prophylaxis.
      The manufacturers suggested stopping clopidogrel 7 days pre-operatively. An
      internet search did not reveal any data on the effect of clopidogrel peri
      operatively in orthopaedic patients. DISCUSSION: Recommendations on stopping
      clopidogrel have evolved from studies conducted on patients undergoing cardio
      thoracic surgery. There is no data available on the effect of clopidogrel in
      orthopaedic practice. Our survey indicates that increased bleeding has not been
      found in patients who continue clopidogrel peri-operatively. Almost half of
      respondents complied with current recommendations, stopping clopidogrel 7 days
      pre-operatively. However there remains a lack of consensus amongst orthopaedic
      surgeons.Currently elective patients should stop clopidogrel 7 days pre
      operatively, and emergency patients should stop clopidogrel on admission, however
      their operation should not be delayed due to clopidogrel usage.

PMID- 17531091
TI  - Differential development of neuronal physiological responsiveness in two human
      neural stem cell lines.
AB  - BACKGROUND: Neural stem cells (NSCs) are powerful research tools for the design
      and discovery of new approaches to neurodegenerative disease. Overexpression of
      the myc family transcription factors in human primary cells from developing
      cortex and mesencephalon has produced two stable multipotential NSC lines
      (ReNcell VM and CX) that can be continuously expanded in monolayer culture.
      RESULTS: In the undifferentiated state, both ReNcell VM and CX are nestin
      positive and have resting membrane potentials of around -60 mV but do not display
      any voltage-activated conductances. As initially hypothesized, using standard
      methods (stdD) for differentiation, both cell lines can form neurons, astrocytes
      and oligodendrocytes according to immunohistological characteristics. However it
      became clear that this was not true for electrophysiological features which
      designate neurons, such as the firing of action potentials. We have thus
      developed a new differentiation protocol, designated 'pre-aggregation
      differentiation' (preD) which appears to favor development of
      electrophysiologically functional neurons and to lead to an increase in
      dopaminergic neurons in the ReNcell VM line. In contrast, the protocol used had
      little effect on the differentiation of ReNcell CX in which dopaminergic
      differentiation was not observed. Moreover, after a week of differentiation with
      the preD protocol, 100% of ReNcell VM featured TTX-sensitive Na+-channels and
      fired action potentials, compared to 25% after stdD. Currents via other voltage
      gated channels did not appear to depend on the differentiation protocol. ReNcell
      CX did not display the same electrophysiological properties as the VM line,
      generating voltage-dependant K+ currents but no Na+ currents or action potentials
      under either stdD or preD differentiation. CONCLUSION: These data demonstrate
      that overexpression of myc in NSCs can be used to generate electrophysiologically
      active neurons in culture. Development of a functional neuronal phenotype may be
      dependent on parameters of isolation and differentiation of the cell lines,
      indicating that not all human NSCs are functionally equivalent.

PMID- 17531092
TI  - Gene expression variation in Down's syndrome mice allows prioritization of
      candidate genes.
AB  - BACKGROUND: Down's syndrome (DS), or trisomy 21, is a complex developmental
      disorder that exhibits many clinical signs that vary in occurrence and severity
      among patients. The molecular mechanisms responsible for DS have thus far
      remained elusive. We argue here that normal variation in gene expression in the
      population contributes to the heterogeneous clinical picture of DS, and we
      estimated the amplitude of this variation in 50 mouse orthologs of chromosome 21
      genes in brain regions of Ts65Dn (a mouse model of DS). We analyzed the RNAs of
      eight Ts65Dn and eight euploid mice by real-time polymerase chain reaction.
      RESULTS: In pooled RNAs, we confirmed that trisomic/euploid gene expression
      ratios were close to 1.5. However, we observed that inter-individual gene
      expression levels spanned a broad range of values. We identified three categories
      of genes: genes with expression levels consistently higher in Ts65Dn than in
      euploids (9, 17, and 7 genes in cerebellum, cortex, and midbrain, respectively);
      genes whose expression levels partially overlap between the two groups (10, 9,
      and 14 genes); and genes with intermingled expression, which cannot be used to
      differentiate trisomics from euploids (12, 5 and 9 genes). Of the genes in the
      first category, App, Cbr1, and Mrps6 exhibited tight regulation in the three
      tissues and are therefore attractive candidates for further research. CONCLUSION:
      This is the first analysis addressing inter-individual gene expression levels as
      a function of trisomy. We propose a strategy allowing discrimination between
      candidates for the constant features of DS and those genes that may contribute to
      the partially penetrant signs of DS.

PMID- 17531093
TI  - Descriptive epidemiology of selected birth defects, areas of Lombardy, Italy,
      1999.
AB  - BACKGROUND: Birth defects are a leading cause of neonatal and infant mortality in
      Italy, however little is known of the etiology of most defects. Improvements in
      diagnosis have revealed increasing numbers of clinically insignificant defects,
      while improvements in treatment have increased the survival of those with more
      serious and complex defects. For etiological studies, prevention, and management,
      it is important to have population-based monitoring which provides reliable data
      on the prevalence at birth of such defects. METHODS: We recently initiated
      population-based birth defect monitoring in the Provinces of Mantova, Sondrio and
      Varese of the Region of Lombardy, northern Italy, and report data for the first
      year of operation (1999). The registry uses all-electronic source files (hospital
      discharge files, death certificates, regional health files, and pathology
      reports) and a proven case-generation methodology, which is described. The data
      were checked manually by consulting clinical records in hospitals. Completeness
      was checked against birth certificates by capture-recapture. Data on cases were
      coded according to the four-digit malformation codes of the International
      Classification of Diseases, Ninth Revision (ICD-9). We present data only on
      selected defects. RESULTS: We found 246 selected birth defects in 12,008 live
      births in 1999, 148 among boys and 98 among girls. Congenital heart defects
      (particularly septal defects) were the most common (90.8/10,000), followed by
      defects of the genitourinary tract (34.1/10, 000) (particularly hypospadias in
      boys), digestive system (23.3/10,000) and central nervous system (14.9/10,000),
      orofacial clefts (10.8/10,000) and Down syndrome (8.3/10,000). Completeness was
      satisfactory: analysis of birth certificates resulted in the addition of two
      birth defect cases to the registry. CONCLUSION: This is the first population
      based analysis on selected major birth defects in the Region. The high birth
      prevalences for septal heart defect and hypospadias are probably due to the
      inclusion of minor defects and lack of coding standardization; the latter problem
      also seems important for other defects. However the data produced are useful for
      estimating the demands made on the health system by babies with birth defects.

PMID- 17531094
TI  - Modular architecture of protein structures and allosteric communications:
      potential implications for signaling proteins and regulatory linkages.
AB  - BACKGROUND: Allosteric communications are vital for cellular signaling. Here we
      explore a relationship between protein architectural organization and shortcuts
      in signaling pathways. RESULTS: We show that protein domains consist of modules
      interconnected by residues that mediate signaling through the shortest pathways.
      These mediating residues tend to be located at the inter-modular boundaries,
      which are more rigid and display a larger number of long-range interactions than
      intra-modular regions. The inter-modular boundaries contain most of the residues
      centrally conserved in the protein fold, which may be crucial for information
      transfer between amino acids. Our approach to modular decomposition relies on a
      representation of protein structures as residue-interacting networks, and removal
      of the most central residue contacts, which are assumed to be crucial for
      allosteric communications. The modular decomposition of 100 multi-domain protein
      structures indicates that modules constitute the building blocks of domains. The
      analysis of 13 allosteric proteins revealed that modules characterize
      experimentally identified functional regions. Based on the study of an additional
      functionally annotated dataset of 115 proteins, we propose that high-modularity
      modules include functional sites and are the basic functional units. We provide
      examples (the Galphas subunit and P450 cytochromes) to illustrate that the
      modular architecture of active sites is linked to their functional
      specialization. CONCLUSION: Our method decomposes protein structures into
      modules, allowing the study of signal transmission between functional sites. A
      modular configuration might be advantageous: it allows signaling proteins to
      expand their regulatory linkages and may elicit a broader range of control
      mechanisms either via modular combinations or through modulation of inter-modular
      linkages.

PMID- 17531095
TI  - The integration of lipid-sensing and anti-inflammatory effects: how the PPARs
      play a role in metabolic balance.
AB  - The peroxisomal proliferating-activated receptors (PPARs) are lipid-sensing
      transcription factors that have a role in embryonic development, but are
      primarily known for modulating energy metabolism, lipid storage, and transport,
      as well as inflammation and wound healing. Currently, there is no consensus as to
      the overall combined function of PPARs and why they evolved. We hypothesize that
      the PPARs had to evolve to integrate lipid storage and burning with the ability
      to reduce oxidative stress, as energy storage is essential for survival and
      resistance to injury/infection, but the latter increases oxidative stress and may
      reduce median survival (functional longevity). In a sense, PPARs may be an
      evolutionary solution to something we call the 'hypoxia-lipid' conundrum, where
      the ability to store and burn fat is essential for survival, but is a 'double
      edged sword', as fats are potentially highly toxic. Ways in which PPARs may
      reduce oxidative stress involve modulation of mitochondrial uncoupling protein
      (UCP) expression (thus reducing reactive oxygen species, ROS), optimising
      forkhead box class O factor (FOXO) activity (by improving whole body insulin
      sensitivity) and suppressing NFkB (at the transcriptional level). In light of
      this, we therefore postulate that inflammation-induced PPAR downregulation
      engenders many of the signs and symptoms of the metabolic syndrome, which shares
      many features with the acute phase response (APR) and is the opposite of the
      phenotype associated with calorie restriction and high FOXO activity. In
      genetically susceptible individuals (displaying the naturally mildly insulin
      resistant 'thrifty genotype'), suboptimal PPAR activity may follow an exaggerated
      but natural adipose tissue-related inflammatory signal induced by excessive
      calories and reduced physical activity, which normally couples energy storage
      with the ability to mount an immune response. This is further worsened when
      pancreatic decompensation occurs, resulting in gluco-oxidative stress and
      lipotoxicity, increased inflammatory insulin resistance and oxidative stress.
      Reactivating PPARs may restore a metabolic balance and help to adapt the
      phenotype to a modern lifestyle.

PMID- 17531096
TI  - Stat3 is tyrosine-phosphorylated through the interleukin-6/glycoprotein 130/Janus
      kinase pathway in breast cancer.
AB  - INTRODUCTION: Signal transducer and activator of transcription 3 (Stat3) is
      constitutively tyrosine-phosphorylated in approximately 50% of primary breast
      carcinomas. A number of different mechanisms responsible for Stat3 activation,
      including abnormal activation of receptor tyrosine kinases, Src, and Janus
      kinases (Jaks), have been implicated in breast cancer. METHODS: We examined six
      breast cancer-derived cell lines expressing high or low levels of tyrosine
      phosphorylated Stat3 (pStat3) as well as primary breast cancer specimens.
      RESULTS: Inhibition of Src or EGFR (epidermal growth factor receptor) tyrosine
      kinases had no effect on pStat3 levels, whereas pan-Jak inhibitor P6 resulted in
      complete abrogation of Stat3 phosphorylation and inhibition of growth. Jaks are
      required for cytokine signaling, and the glycoprotein 130 (gp130) receptor
      associated Jaks are known mediators of Stat3 phosphorylation. Blockade of the
      gp130 receptor or sequestration of the interleukin-6 (IL-6) ligand led to a
      decrease of pStat3 levels. Conditioned media from those cell lines expressing
      high levels of pStat3 contained IL-6 and were capable of stimulating Stat3
      phosphorylation. We examined IL-6 levels in primary breast tumors and found a
      positive correlation between pStat3 and IL-6 expression. CONCLUSION: In summary,
      a principal mechanism of Stat3 activation in breast cancer is through the IL
      6/gp130/Jak pathway.

PMID- 17531097
TI  - Challenges and strategies of children and adolescents with inflammatory bowel
      disease: a qualitative examination.
AB  - BACKGROUND: The aims of this study were to understand the lived experience and
      elements of quality of life as depicted by children and adolescents with
      inflammatory bowel disease (IBD). METHODS: Eighty participants with IBD, ranging
      in age from 7 to 19 years, were interviewed about the impact of IBD on their
      daily lives. RESULTS: Findings demonstrated that IBD profoundly affects children
      and adolescents. These young patients experience concerns and discomfort as a
      result of IBD symptoms and treatments. They commonly feel, in varying degrees, a
      sense of vulnerability and diminished control over their lives and future, and
      perceive themselves as "different" from healthy peers and siblings. Despite these
      negative impacts, participants also described effective means of coping with IBD,
      and reported that support from family members and friends contributes to coping.
      A positive attitude and other strategies were also described as strengths
      contributing to quality of life. CONCLUSION: Clinical assessments need to
      consider the experiences and perceptions of children as they manage their IBD.
      Implications for clinical practice are discussed.

PMID- 17531098
TI  - Hin-mediated DNA knotting and recombining promote replicon dysfunction and
      mutation.
AB  - BACKGROUND: The genetic code imposes a dilemma for cells. The DNA must be long
      enough to encode for the complexity of an organism, yet thin and flexible enough
      to fit within the cell. The combination of these properties greatly favors DNA
      collisions, which can knot and drive recombination of the DNA. Despite the well
      accepted propensity of cellular DNA to collide and react with itself, it has not
      been established what the physiological consequences are. RESULTS: Here we
      analyze the effects of recombined and knotted plasmids in E. coli using the Hin
      site-specific recombination system. We show that Hin-mediated DNA knotting and
      recombination (i) promote replicon loss by blocking DNA replication; (ii) block
      gene transcription; and (iii) cause genetic rearrangements at a rate three to
      four orders of magnitude higher than the rate for an unknotted, unrecombined
      plasmid. CONCLUSION: These results show that DNA reactivity leading to recombined
      and knotted DNA is potentially toxic and may help drive genetic evolution.

PMID- 17531099
TI  - The scientific impact of the Sir Charles Bell Society in head and face medicine.

PMID- 17531100
TI  - Cross-study analysis of gene expression data for intermediate neuroblastoma
      identifies two biological subtypes.
AB  - BACKGROUND: Neuroblastoma patients show heterogeneous clinical courses ranging
      from life-threatening progression to spontaneous regression. Recently, gene
      expression profiles of neuroblastoma tumours were associated with clinically
      different phenotypes. However, such data is still rare for important patient
      subgroups, such as patients with MYCN non-amplified advanced stage disease.
      Prediction of the individual course of disease and optimal therapy selection in
      this cohort is challenging. Additional research effort is needed to describe the
      patterns of gene expression in this cohort and to identify reliable prognostic
      markers for this subset of patients. METHODS: We combined gene expression data
      from two studies in a meta-analysis in order to investigate differences in gene
      expression of advanced stage (3 or 4) tumours without MYCN amplification that
      show contrasting outcomes (alive or dead) at five years after initial diagnosis.
      In addition, a predictive model for outcome was generated. Gene expression
      profiles from 66 patients were included from two studies using different
      microarray platforms. RESULTS: In the combined data set, 72 genes were identified
      as differentially expressed by meta-analysis at a false discovery rate (FDR) of
      8.33%. Meta-analysis detected 34 differentially expressed genes that were not
      found as significant in either single study. Outcome prediction based on data of
      both studies resulted in a predictive accuracy of 77%. Moreover, the genes that
      were differentially expressed in subgroups of advanced stage patients without
      MYCN amplification accurately separated MYCN amplified tumours from low stage
      tumours without MYCN amplification. CONCLUSION: Our findings support the
      hypothesis that neuroblastoma consists of two biologically distinct subgroups
      that differ by characteristic gene expression patterns, which are associated with
      divergent clinical outcome.

PMID- 17531101
TI  - The evaluation of renal ischaemic damage: the value of CD10 monoclonal antibody
      staining and of biochemical assessments of tissue viability.
AB  - BACKGROUND: It is well recognised that there is often a disparity between the
      structural changes observed in the kidney following renal injury and the function
      of the organ. For this reason, we carried out studies to explore possible means
      of studying and quantifying the severity of renal ischaemic damage using a
      laboratory model. METHODS: To do this, freshly isolated rabbit kidney tissue was
      subjected to warm (37 degrees C) or cold (1 degrees C) ischaemia for 20 hours.
      Following this, the tissue was stained using Haematoxylin and Eosin (H+E),
      Periodic Schiff reagent (PAS) and the novel monoclonal antibody CD10 stain.
      Additionally, ischaemic damage to the kidneys was assessed by biochemical tests
      of tissue viability using formazan-based colorimetry. RESULTS: CD 10 antibody
      intensely stained the brush border of control kidney tissue with mild or no
      cytoplasmic staining. Cell injury was accompanied by a redistribution of CD10
      into the lumen and cell cytoplasm. There was good correlation between a score of
      histological damage using the CD 10 monoclonal antibody stain and the biochemical
      assessment of viability. Similarly, a score of histological damage using
      traditional PAS staining correlated well with that using the CD10 antibody stain.
      In particular, the biochemical assay and the monoclonal antibody staining
      techniques were able to demonstrate the efficacy of Soltran (this solution is
      used cold to preserve freshly isolated human kidneys prior to transplantation) in
      preserving renal tissue at cold temperatures compared to other randomly selected
      solutions. CONCLUSION: We conclude that the techniques described using the CD10
      monoclonal antibody stain may be helpful in the diagnosis and assessment of
      ischaemic renal damage. In addition, biochemical tests of viability may have an
      important role in routine histopathological work by giving additional information
      about cellular viability which may have implications on the function of the
      organ.

PMID- 17531102
TI  - Assessing the risk of self-diagnosed malaria in urban informal settlements of
      Nairobi using self-reported morbidity survey.
AB  - BACKGROUND: Because of the belief that Nairobi is a low risk zone for malaria,
      little empirical data exists on malaria risk in the area. The aim of this study
      was to explore the risk of perceived malaria and some associated factors in
      Nairobi informal settlements using self-reported morbidity survey. METHODS: The
      survey was conducted from May to August 2004 on 7,288 individuals in two informal
      settlements of Nairobi. Participants were asked to report illnesses they
      experienced in the past 14 days. Logistic regression was used to estimate the
      odds of perceived-malaria. The model included variables such as site of
      residence, age, ethnicity and number of reported symptoms. RESULTS: Participants
      reported 165 illnesses among which malaria was the leading cause (28.1%). The
      risk of perceived-malaria was significantly higher in Viwandani compared to
      Korogocho (OR 1.61, 95%CI: 1.10-2.26). Participants in age group 25-39 years had
      significantly higher odds of perceived-malaria compared to those under-five years
      (OR 2.07, 95%CI: 1.43-2.98). The Kikuyu had reduced odds of perceived-malaria
      compared to other ethnic groups. Individuals with five and more symptoms had
      higher odds compared to those with no symptoms (OR 23.69, 95%CI: 12.98-43.23).
      CONCLUSION: Malaria was the leading cause of illness as perceived by the
      residents in the two informal settlements. This was rational as the number of
      reported symptoms was highly associated with the risk of reporting the illness.
      These results highlight the need for a more comprehensive assessment of malaria
      epidemiology in Nairobi to be able to offer evidence-based guidance to policy on
      malaria in Kenya and particularly in Nairobi.

PMID- 17531103
TI  - Mirizzi syndrome type IV associated with cholecystocolic fistula: a very rare
      condition--report of a case.
AB  - BACKGROUND: Mirizzi syndrome is a rare complication of prolonged cholelithiasis
      with presence of large, impacted gallstone into the Hartman's pouch, causing
      chronic extrinsic compression of common bile duct (CBD). Fistula formation
      between the CBD and the gallbladder may represent an outcome of that condition.
      According to Mirizzi's classification and Csendes's subclassification, Mirizzi
      syndrome type IV represents the most uncommon type (4%). Spontaneous biliary
      enteric fistulas have also been rarely reported (1.2-5%) in a large series of
      cholecystectomies. Cholecystocolic fistula is the most infrequent biliary enteric
      fistula, causing significant morbidity and representing a diagnostic challenge.
      CASE PRESENTATION: We describe a very rare, to our knowledge, combination of
      Mirizzi syndrome type IV and cholecystocolic fistula. A 52 year old male,
      presented to our clinic complaining of episodic diarrhea (monthly episodes
      lasting 16 days), high temperature (38 degrees C-39 degrees C), right upper
      quadrant pain without jaundice. The definitive diagnosis was made
      intraoperatively. Magnetic Resonance Imaging (MRI) and Endoscopic Retrograde
      Cholangiopancreatography (ERCP) demonstrated the presence of Mirizzi syndrome
      with cholecystocolic fistula formation. The patient was operated upon, and
      cholecystectomy, cholecystocolic fistula excision and Roux-en-Y biliary-enteric
      anastomosis were undertaken with excellent post-operative course. CONCLUSION:
      Appropriate biliary tree imaging with ERCP and MRI/MRCP is essential for the
      diagnosis of Mirizzi syndrome and its complications. Cholecystectomy, fistula
      excision and biliary-enteric anastomosis with Roux-en-Y loop appears to be the
      most appropriate surgical intervention in order to avoid damage to Calot's
      triangle anatomic elements. Particularly in our case, ERCP was a valuable
      diagnostic tool that Mirizzi syndrome type IV and cholecystocolic fistula.

PMID- 17531104
TI  - Optimization and clinical validation of a pathogen detection microarray.
AB  - DNA microarrays used as 'genomic sensors' have great potential in clinical
      diagnostics. Biases inherent in random PCR-amplification, cross-hybridization
      effects, and inadequate microarray analysis, however, limit detection sensitivity
      and specificity. Here, we have studied the relationships between viral
      amplification efficiency, hybridization signal, and target-probe annealing
      specificity using a customized microarray platform. Novel features of this
      platform include the development of a robust algorithm that accurately predicts
      PCR bias during DNA amplification and can be used to improve PCR primer design,
      as well as a powerful statistical concept for inferring pathogen identity from
      probe recognition signatures. Compared to real-time PCR, the microarray platform
      identified pathogens with 94% accuracy (76% sensitivity and 100% specificity) in
      a panel of 36 patient specimens. Our findings show that microarrays can be used
      for the robust and accurate diagnosis of pathogens, and further substantiate the
      use of microarray technology in clinical diagnostics.

PMID- 17531105
TI  - Panitumumab with irinotecan/leucovorin/5-fluorouracil for first-line treatment of
      metastatic colorectal cancer.
AB  - PURPOSE: Panitumumab is a fully human monoclonal antibody directed against the
      epidermal growth factor receptor and is indicated for patients with metastatic
      colorectal cancer (mCRC) who have experienced disease progression after standard
      chemotherapy. We conducted this phase II study to assess the ability of
      panitumumab to be administered with first-line irinotecan-containing regimens in
      patients with mCRC. PATIENTS AND METHODS: This was a 2-part multicenter study of
      panitumumab 2.5 mg/kg weekly with irinotecan, 5-fluorouracil (5-FU), and
      leucovorin. Part 1 used bolus 5-FU (IFL), and part 2 used infusional 5-FU
      (FOLFIRI). Tolerability (measured by grade 3/4 diarrhea) was the primary
      endpoint. Objective response, progression-free survival, overall survival, and
      safety were also examined. RESULTS: Nineteen patients in part 1 and 24 patients
      in part 2 received panitumumab plus chemotherapy. Grade 3/4 diarrhea occurred in
      11 patients (58%) in part 1 and 6 patients (25%) in part 2. All patients had a
      skin-related toxicity (no grade 4 events). Objective response rates were 46% in
      part 1 and 42% in part 2. Disease control rates were 74% in part 1 and 79% in
      part 2. Median progression-free survival (95% confidence interval) was 5.6 months
      (4.4-8.3 months) for part 1 and 10.9 months (7.7-22.5 months) for part 2. Median
      overall survival (95% confidence interval) was 17 months (13.7 months to not
      estimable) for part 1 and 22.5 months (14.4 months to not estimable) for part 2.
      CONCLUSION: In patients with mCRC, panitumumab/IFL was not well tolerated.
      Panitumumab/FOLFIRI was well tolerated, showed promising activity, and is
      undergoing further investigation.

PMID- 17531106
TI  - Predictive value of MSH2 gene expression in colorectal cancer treated with
      capecitabine.
AB  - PURPOSE: The objective of the present study was to evaluate the gene expression
      of the DNA mismatch repair gene MSH2 as a predictive marker in advanced
      colorectal cancer (CRC) treated with first-line capecitabine. PATIENTS AND
      METHODS: Microdissection of paraffin-embedded tumor tissue, RNA extraction, and
      quantitative polymerase chain reaction were performed on tumors obtained from 37
      patients with advanced CRC. RESULTS: The median relative gene expression of MSH2
      was 0.65 (quartiles 0.5-0.8) in nonresponders and 1.25 (quartiles 0.92-1.38) for
      responders (P = 0.038). High expression of MSH2 was associated with a hazard
      ratio of 0.5 (95% confidence interval, 0.23-1.11; P = 0.083) in survival
      analysis. CONCLUSION: The higher gene expression of MSH2 in responders and the
      trend for predicting overall survival indicates a predictive value of this marker
      in the treatment of advanced CRC with capecitabine.

PMID- 17531107
TI  - Mitomycin-C/5-fluorouracil/leucovorin and hyperfractionated radiation therapy for
      rectal carcinoma: a phase II study with long-term follow-up.
AB  - PURPOSE: Preoperative chemotherapy followed by surgery and adjuvant chemotherapy
      is a standard treatment for most patients with rectal cancer. We aimed to
      determine efficacy and tolerability of preoperative mitomycin, fluorouracil (5
      FU), and leucovorin (LV) concurrent with hyperfractionated radiation therapy (RT)
      followed by surgery and adjuvant chemotherapy. PATIENTS AND METHODS: Patients
      with clinical stage II/III disease were treated with mitomycin 10 mg/m(2) on day
      1, continuous venous infusion 5-FU 600 mg/m(2) per day for 96 hours, and oral LV
      25 mg every 6 hours on days 1-5. All patients received concurrent RT in fractions
      of 150 cGy twice daily beginning on day 1. Unfixed tumors received 3000 cGy,
      whereas fixed tumors received a dose of 4500 cGy. Patients then underwent
      resection and postoperative adjuvant chemotherapy with oral LV and continuous
      venous infusion 5-FU 600 mg/m(2) per day on days 1-5 on a 28-day cycle for 6
      cycles. Primary endpoints were to determine the rate of pathologic response and
      downstaging, long-term locoregional control, progression-free survival, and
      overall survival. RESULTS: Between the years 1993 and 2000, 83 patients were
      enrolled. Eighteen patients (31%) were downstaged. Six patients (7%) had
      pathologic complete response. Median follow-up was 62 months with a 5-year
      overall survival of 71%. Local control rate was 96%. Treatment was well tolerated
      with stomatitis, diarrhea, and radiation proctitis being the most common
      toxicities. CONCLUSION: This regimen is effective in the treatment of rectal
      carcinoma. The favorable toxicity profile of mitomycin and hyperfractionated RT
      allows these strategies to be utilized with the newer chemotherapies for this
      disease.

PMID- 17531108
TI  - Hypoxia-induced lactate dehydrogenase expression and tumor angiogenesis.
AB  - The aim of this review is to discuss the basic science of tumor angiogenesis and
      recent clinical trial results with angiogenic inhibitors. Colorectal cancer (CRC)
      continues to be a major cause of all new cancer cases and cancer-related deaths
      in North America. Although advances in chemotherapy have increased overall
      survival for patients suffering from metastatic CRC, the survival rate continues
      to be poor. In order to develop new and more effective therapies for advanced
      CRC, it is important to understand the basic biologic processes that govern tumor
      growth. This review will focus on pathways involved in stimulating tumor growth
      and angiogenesis. Recent excitement has been generated by the clinical efficacy
      of targeted antiangiogenic therapy against growth factors important in
      angiogenesis and tumor proliferation. By presenting the basic biology of tumor
      growth and angiogenesis, we will attempt to explain the therapeutic effects of
      different angiogenesis inhibitors and speculate how combination treatments with
      these agents might be beneficial.

PMID- 17531109
TI  - Reversible grade 4 hyperbilirubinemia in a patient with UGT1A1 7/7 genotype
      treated with irinotecan and cetuximab.
AB  - Irinotecan-induced gastrointestinal toxicities are common and typically present
      in the form of diarrhea or nausea and vomiting. However, severe
      hyperbilirubinemia (grade 3/4) has not been previously reported in association
      with this chemotherapeutic agent. We report a case of prolonged grade 4
      hyperbilirubinemia after a single dose of irinotecan at 125 mg/m(2). This severe
      toxicity was attributed to a UGT1A1 7/7 genotype and resolved to grade 2 after 8
      weeks of supportive care. This case outlines the possibility of severe hepatic
      toxicity with moderate doses of irinotecan in patients with a UGT1A1 7/7
      genotype. Despite the severity and prolonged duration of the associated
      irinotecan-induced hepatic toxicity, the management of similar cases should focus
      on intensive supportive measures because the toxicity is likely to resolve
      eventually.

PMID- 17531110
TI  - Expressed sequence tags analysis of a liver tissue cDNA library from a highly
      inbred minipig line.
AB  - BACKGROUND: Porcine liver performing efficient physiological functions in the
      human body is prerequisite for successful liver xenotransplantation. However, the
      protein differences between pig and human remain largely unexplored. Therefore,
      we investigated the liver expression profile of a highly inbred minipig line.
      METHODS: A cDNA library was constructed from liver tissue of an inbred Banna
      minipig. Two hundred randomly selected clones were sequenced then analysed by
      BLAST programme. RESULTS: Alignments of the sequences showed 44% encoded
      previously known porcine genes. Among the 56% unknown genes, sequences of 72
      clones had high similarities with known genes of other species and the
      similarities to human were mostly above 0.80. The other 40 clones showing no
      similarity to genes in National Centre for Biotechnology Information are newly
      discovered, expressed sequence tags specific to liver of inbred Banna minipig.
      Twenty-two of the 200 clones had full length encoding regions, 38 complete 5'
      terminal sequences and 140 complete 3' terminal sequences. CONCLUSION: These
      newly discovered expression sequences may be an important resource for research
      involving physiological characteristics and medical usage of inbred pigs and
      contribute to matching studies in xenotransplantation.

PMID- 17531111
TI  - Inducing effects of hepatocyte growth factor on the expression of vascular
      endothelial growth factor in human colorectal carcinoma cells through MEK and
      PI3K signaling pathways.
AB  - BACKGROUND: Vascular endothelial growth factor plays a key role in human
      colorectal carcinoma invasion and metastasis. However, the regulation mechanism
      remains unknown. Recent studies have shown that several cytokines can regulate
      the expression of vascular endothelial growth factor in tumor cells. In this
      study, we investigated whether hepatocyte growth factor can regulate the
      expression of vascular endothelial growth factor in colorectal carcinoma cells.
      METHODS: Hepatocyte growth factor and vascular endothelial growth factor in human
      serum were measured by ELISA. The mRNA level of vascular endothelial growth
      factor was analyzed by reverse transcription-PCR. Western blot assay was
      performed to evaluate levels of c-Met and several other proteins involved in the
      MAPK and PI3K signaling pathways in colorectal carcinoma cells. RESULTS: Serum
      hepatocyte growth factor and vascular endothelial growth factor were
      significantly increased in colorectal carcinoma subjects. In vitro extraneous
      hepatocyte growth factor markedly increased protein and mRNA levels of vascular
      endothelial growth factor in colorectal carcinoma cells. Hepatocyte growth factor
      induced phosphorylation of c-Met, ERK1/2 and AKT in a dose-dependent manner.
      Specific inhibitors on MEK and PI3K inhibited the hepatocyte growth factor
      induced expression of vascular endothelial growth factor in colorectal carcinoma
      cells. CONCLUSION: This present study indicates that hepatocyte growth factor
      upregulates the expression of vascular endothelial growth factor in colorectal
      carcinoma cells via the MEK/ERK and PI3K/AKT signaling pathways.

PMID- 17531112
TI  - Antitumour effects on human colorectal carcinomas cells by stable silencing of
      phospholipase C-gamma 1 with lentivirus-delivered siRNA.
AB  - BACKGROUND: In most colorectal carcinomas, the level of phospholipase C (PLC)
      gamma 1 expression is greatly elevated. Increased expression of PLC-gamma 1 may
      play an important role in colon carcinogenesis, but the mechanism is not well
      known. The aim of this study was to evaluate the role of PLC-gamma 1 in colon
      carcinogenesis by using recombinant lentivirus that stably suppressed the PLC
      gamma 1 expression in human colorectal carcinoma LoVo cells. METHODS: Recombinant
      lentivirus producing PLC-gamma 1 siRNA were prepared. After LoVo cells were
      transduced by each lentivirus, stably transduced cells were selected by
      Blasticidin. The protein and mRNA expression of PLC-gamma 1 were examined by
      Western-blot and reverse transcription-polymerase chain reaction (RT-PCR)
      analysis, and the effects of the lentivirus on the cell adhesion, migration and
      apoptosis were analyzed. RESULTS: Stable LoVo cell line deficient in PLC-gamma 1,
      was established. Notably, PLC-gamma 1 was silenced without affecting the levels
      of other subtypes of PLC so that the role of PLC-gamma 1 in colon carcinogenesis
      could be examined. Silencing of endogenous PLC-gamma 1 resulted in efficient
      inhibition of the adhesion and migration of LoVo cells in vitro and a great
      increase of 5-fluorouracil induced apoptosis (30%-40%) of LoVo cells.
      CONCLUSIONS: PLC-gamma 1 may play an important role in metastasis and anti
      apoptosis in human colorectal carcinomas.

PMID- 17531113
TI  - Inhibition of telomerase with human telomerase reverse transcriptase antisense
      enhances tumor necrosis factor-alpha-induced apoptosis in bladder cancer cells.
AB  - BACKGROUND: Telomerase activity is found in 85%-90% of all human cancers but not
      in their adjacent normal cells. Human telomerase reverse transcriptase (hTERT) is
      an essential component in the telomerase complex that plays an important role in
      telomerase activity. This study investigated the effect of the telomerase
      inhibition with an hTERT antisense oligodeoxynucleotide (ODN) in bladder cancer
      cells (T24) on tumor necrosis factor-alpha (TNF-alpha)-induced apoptosis.
      METHODS: Antisense phosphorothioate oligodeoxynucleotide (AS PS-ODN) was
      synthesized and purified. Telomerase activity was measured by polymerase chain
      reaction enzyme-linked immunoassay (PCR-ELISA). hTERT mRNA expression was
      measured by reverse transcription polymerase chain reaction (RT-PCR) assay and a
      gel-image system. hTERT protein was detected by immunochemistry and flow
      cytometry. Cell viability was measured by the 3-(4, 5-dimethylthiazol-2-yl)-2, 5
      Diphenyltetrazolium (MTT) assay. Cell apoptosis was observed by a morphological
      method and determined by flow cytometry. RESULTS: AS PS-ODN significantly
      inhibited telomerase activity and decreased the levels of hTERT mRNA which
      preceded the decline in the telomerase activity. AS PS-ODN significantly reduced
      the percentage of positive cells expressing hTERT protein following the decline
      of hTERT mRNA levels. There was no difference seen in the telomerase activity,
      hTERT mRNA expression or the protein levels between the sense phosphorothioate
      oligodeoxynucleotide (SPS-ODN) and the control group. AS PS-ODN treatment
      significantly decreased the cell viability and enhanced the apoptotic rate of T24
      cells in response to TNF-alpha while there was no difference in cell viability
      and apoptotic rate between the S PS-ODN and the control group. CONCLUSIONS: AS PS
      ODN can significantly inhibit telomerase activity by downregulating the hTERT
      mRNA and protein expression. Treatment with AS PS-ODN may be a potential and most
      promising strategy for bladder cancer with telomerase activity.

PMID- 17531115
TI  - Preliminary clinical outcomes of percutaneous kyphoplasty with Sky-bone expander.
AB  - BACKGROUND: Percutaneous kyphoplasty (PKP) using balloon expander has been proved
      to be effective in the treatment of painful vertebral compression fractures.
      Recently, Sky-bone expander, an alternative bone expander for PKP has been
      developed. The purpose of this study was to show our preliminary clinical
      outcomes of PKP with Sky-bone expander. METHODS: PKP with Sky-bone expander was
      performed in 25 patients (30 vertebrae). The operation time, bleeding volume,
      cement volume injected were recorded. The pain and functional activities of the
      patients before and after the operation were compared using Wilcoxon signed-rank
      test. The cement distribution in the vertebrae, vertebral height restoration, and
      kyphosis correction after the procedure were evaluated by radiography. The pre-
      and post-operative absolute values of the vertebral height and kyphotic angle
      were compared by paired-sample t test. All the patients were followed up by
      telephone or clinic consulting after being discharged from our hospital. RESULTS:
      The procedure was performed successfully in all the patients. Bipedicular
      injection was used in 2 of the patients, and unipedicular injection was made in
      the others. The operation time ranged from 25 to 120 minutes (45 minutes per
      vertebra on average). The average bleeding volume was about 20 ml.
      Polymethylmethacrylate 1.5-5.0 ml (mean, (3.15+/-0.78) ml) was injected through
      each pedicle into all the patients except one, who received calcium sulphate 3.5
      ml instead. The patients were followed up for 12-15 months (13.5 months on
      average). The mean visual analogue scale (VAS) score, Oswestry Disability Index,
      anterior, midline, and posterior vertebral height, and kyphotic angle of the
      patients were improved significantly at the end of the follow-up compared with
      those before the operation. (2.5+/-1.3, 35.1%, (20.94+/-6.15) mm, (20.26+/-4.59)
      mm, (26.72+/-3.49) mm, and 8.2 degrees vs. 8.5+/-1.9, 61.2%, (19.11+/-6.72) mm,
      (15.88+/-5.73) mm, (25.78+/-3.67) mm, and 17.3 degrees; all P<0.05). The cement
      distribution with unipedicular injection was mostly limited within the injection
      site in the vertebral body. Cement extravasation was seen at ten levels (33.3%).
      CONCLUSIONS: PKP with Sky-bone expander is an effective and relatively safe
      alternative to the PKP using balloon expander. It can relieve pain, improve
      physical function, and restore the height of the collapsed vertebrae, but the
      cement extravasation is unsolved.

PMID- 17531116
TI  - Computerized geometric features of carpal bone for bone age estimation.
AB  - BACKGROUND: Bone age development is one of the significant indicators depicting
      the growth status of children. However, bone age assessment is an heuristic and
      tedious work for pediatricians. We developed a computerized bone age estimation
      system based on the analysis of geometric features of carpal bones. METHODS: The
      geometric features of carpals were extracted and analyzed to judge the bone age
      of children by computerized shape and area description. Four classifiers, linear,
      nearest neighbor, back-propagation neural network, and radial basis function
      neural network, were adopted to categorize bone age. Principal component and
      discriminate analyses were employed to improve assorting accuracy. RESULTS: The
      hand X-ray films of 465 boys and 444 girls served as our database. The features
      were extracted from carpal bone images, including shape, area, and sequence. The
      proposed normalization area ratio method was effective in bone age classification
      by simulation. Besides, features statistics showed similar results between the
      standard of the Greulich and Pyle atlas and our database. CONCLUSIONS: The bone
      area has a higher discriminating power to judge bone age. The ossification
      sequence of trapezium and trapezoid bones between Taiwanese and the atlas of the
      GP method is quite different. These results also indicate that carpal bone
      assessment with classification of neural networks can be correct and practical.

PMID- 17531117
TI  - Differentiation of bone marrow-derived mesenchymal stem cells from diabetic
      patients into insulin-producing cells in vitro.
AB  - BACKGROUND: Stem cells, which have the ability to differentiate into insulin
      producing cells (IPCs), would provide a potentially unlimited source of islet
      cells for transplantation and alleviate the major limitations of availability and
      allogeneic rejection. Therefore, the utilization of stem cells is becoming the
      most promising therapy for diabetes mellitus (DM). Here, we studied the
      differentiation capacity of the diabetic patient's bone marrow-derived
      mesenchymal stem cells (MSCs) and tested the feasibility of using MSCs for beta
      cell replacement. METHODS: Bone marrow-derived MSCs were obtained from 10 DM
      patients (5 type 1 DM and 5 type 2 DM) and induced to IPCs under a three-stage
      protocol. Representative cell surface antigen expression profiles of MSCs were
      analysed by flow cytometric analysis. Reverse transcription-polymerase chain
      reaction (RT-PCR) was performed to detect multiple genes related to pancreatic
      beta-cell development and function. The identity of the IPCs was illustrated by
      the analysis of morphology, ditizone staining and immunocytochemistry. Release of
      insulin by these cells was confirmed by immunoradioassay. RESULTS: Flow
      cytometric analysis of MSCs at passage 3 showed that these cells expressed high
      levels of CD29 (98.28%), CD44 (99.56%) and CD106 (98.34%). Typical islet-like
      cell clusters were observed at the end of the protocol (18 days). Ditizone
      staining and immunohistochemistry for insulin were both positive. These
      differentiated cells at stage 2 (10 days) expressed nestin, pancreatic duodenal
      homeobox-1 (PDX-1), Neurogenin3, Pax4, insulin, glucagon, but at stage 3 (18
      days) we observed the high expression of PDX-1, insulin, glucagon. Insulin was
      secreted by these cells in response to different concentrations of glucose
      stimulation in a regulated manner (P<0.05). CONCLUSIONS: Bone marrow-derived MSCs
      from DM patients can differentiate into functional IPCs under certain conditions
      in vitro. Using diabetic patient's own bone marrow-derived MSCs as a source of
      autologous IPCs for beta-cell replacement would be feasible.

PMID- 17531118
TI  - Role of p38 mitogen-activated protein kinases in cardioprotection of morphine
      preconditioning.
AB  - BACKGROUND: p38 mitogen-activated protein kinases (MAPK) in ischemic
      preconditioning (IPC) may be essential to cardioprotection. We assessed whether
      protective effect of morphine-induced preconditioning (MPC) on myocardial
      ischemia and reperfusion injury in rat hearts involved p38 MAPK activation.
      METHODS: Male Spargue-Dawley rats (weighing 300-350 g) were randomly assigned to
      1 of the following 8 groups: control (CON, saline vehicle, n=9), SB 203580 (SB, a
      p38 MAPK inhibitor, n=6), MPC (n=6), IPC (n=9), SB+MPC, SB+IPC, MPC+SB, and
      IPC+SB (n=6). Infarct sizes (IS), a percentage of the area at risk (AAR), were
      determined by triphenyltetrazolium (TTC) staining. Tissue samples were processed
      from the entire AAR of left ventricle for the determination of p38 MAPK protein
      expression (5 hearts/group). The bands representing the proteins were visualized
      using an enhanced chemiluminescence detection system. RESULTS: The IS/AAR was
      significantly reduced by IPC (12.9+/-1.6)% or MPC (25.3+/-2.9)% compared to the
      control (52.7+/-5.5)%. SB 203580 administered prior to preconditioning abolished
      the effect of IPC (SB+IPC: (43.8+/-2.6)%, P>0.05 vs CON, P<0.01 vs IPC), but not
      MPC (SB+MPC: (30.7+/-0.9)%, P<0.01 vs CON, P>0.05 vs MPC). Treatment with SB
      203580 prior to sustained ischemia diminished the protective effect of both MPC
      (MPC+SB: (42.4+/-2.9)%, P>0.05 vs CON) and IPC (IPC+SB: (52.0+/-2.5)%, P>0.05 vs
      CON) on IS/AAR. In the IPC group, phospho-p38 MAPK protein increased
      significantly within 5 minutes into ischemia and remained elevated at 30 minutes
      into reperfusion, while phospho-p38 MAPK protein in the MPC group only increased
      significantly at 30 minutes into reperfusion. CONCLUSION: The activation of p38
      MAPK just acts as a mediator of MPC, whereas it acts as both a trigger and a
      mediator in IPC.

PMID- 17531119
TI  - Effect of renin-angiotensin-aldosterone system gene polymorphisms on blood
      pressure response to antihypertensive treatment.
AB  - BACKGROUND: The renin-angiotensin-aldosterone system (RAAS) is important for the
      development of essential hypertension, and many antihypertensive drugs target it.
      This study was undertaken to determine whether polymorphisms in the renin
      angiotensin-aldosterone system are related to the blood pressure (BP) response to
      diuretic treatment in a Chinese Han ethnic population. METHODS: Fifty-four
      patients with essential hypertension received hydrochlorothiazide (12.5 mg, once
      daily) as monotherapy for four weeks. Seven polymorphisms in RAAS genes were
      genotyped by gene chip technology. The relationship between these polymorphisms
      and the change in blood pressure was observed after the 4-week treatment.
      RESULTS: The patients with angiotensinogen (AGT) -6G allele showed a greater
      reduction in diastolic BP (P=0.025) and mean BP (P=0.039) than those carrying AA
      genotype. Patients carrying aldosterone synthase (CYP11B2) CC genotype exhibited
      a greater BP reduction than those carrying CT and TT genotypes (systolic BP:
      P=0.030; diastolic BP: P=0.026; mean BP: P=0.003). In addition, patients with a
      combination of CYP11B2 CC genotype and angiotensin converting enzyme (ACE) D
      allele might have a more pronounced reduction of systolic BP than those with any
      other genotypic combinations of the two genes (P=0.007). CONCLUSIONS: AGT-6G
      allele, CYP11B2 -344CC genotype and its combination with ACE D allele are
      associated with BP response to hydrochlorothiazide treatment. Larger studies are
      warranted to validate this finding.

PMID- 17531120
TI  - Effects of advanced glycation end products on renal fibrosis and oxidative stress
      in cultured NRK-49F cells.
AB  - BACKGROUND: Advanced glycation end products (AGEs) play a critical role in the
      development of diabetic nephropathy. Reactive oxygen species (ROS) may play a
      critical role in AGEs induced growth factor expression. In this study, the
      effects of AGEs on transforming growth factor beta1 (TGF-beta1), connective
      tissue growth factor (CTGF) and fibronectin (Fn) mRNA expression and oxidative
      stress in cultured NRK-49F cells were examined. METHODS: NRK-49F cells were
      incubated with medium containing different doses of AGEs (50, 100 or 200
      microg/ml) for 24 hours, or with AGEs 100 microg/ml for different times (0, 12,
      24 or 48 hours). Cells in the serum-free medium or medium containing 25 mmol/L
      glucose were controls. Cells were treated with 25 mmol/L glucose and 100
      microg/ml AGEs for 24 hours to determine the effects between AGEs and glucose. We
      clarified the role of antioxidant by pretreating cells with N-acetylcysteine (10
      mmol/L), ginkgo biloba extract (50 or 100 mg/L) for 24 hours and with 100
      microg/ml AGEs for further 24 hours. Alamarblue dye assay was used to analyze
      cell growth; intracellular ROS generation was measured by flow cytometry;
      intracellular glutathione by fluorescence spectrophotometry; expressions of TGF
      beta1, CTGF and Fn mRNA by semiquantitative RT-PCR. RESULTS: AGEs significantly
      increased the expressions of TGF-beta1, CTGF, Fn mRNA and intracellular ROS
      generation, and decreased the glutathion level in NRK-49F cells in dose- and time
      dependent manners. High glucose and AGEs together significantly increased the
      expression of TGF-beta1, CTGF and Fn mRNA, compared with AGEs and high glucose
      separately. Preincubation with N-acetylcysteine or ginkgo biloba extract
      increased GSH level, suppressed AGEs-induced oxidative stress and TGF-beta1, CTGF
      and Fn mRNA overexpression. CONCLUSIONS: AGEs can significantly increase
      expression of TGF-beta1, CTGF, Fn mRNA in NRK-49F cells through enhancement of
      oxidative stress. The accumulation of AGEs may play a pivotal role in the
      pathogenesis of tubulointerstitial fibrosis in diabetic nephropathy. Suppression
      of AGEs induced TGF-beta1, CTGF and Fn mRNA overexpression in renal fibroblasts
      through inhibition of oxidative stress may be a mechanism underlying effect of
      ginkgo biloba extract in diabetic nephropathy. In addition, antioxidant therapy
      may help prevent AGEs accumulation and its induced damage.

PMID- 17531121
TI  - Effects of curcumin on peroxisome proliferator-activated receptor gamma
      expression and nuclear translocation/redistribution in culture-activated rat
      hepatic stellate cells.
AB  - BACKGROUND: The function of peroxisome proliferator-activated receptor gamma
      (PPARgamma) in hepatic fibrogenesis remains largely unknown. Curcumin is a
      natural substance extracted form Curcuma Longa Linn and has a variety of
      pharmacological effects. In this study, the effects of curcumin on the
      proliferation, activation and apoptosis of rat hepatic stellate cells (HSCs)
      through PPARgamma signaling were investigated. METHODS: HSCs were isolated from
      the normal Sprague Dawley rats through in situ perfusion of the liver with
      Pronase E and density-gradient centrifugation with Nycodenz. Cells were treated
      with curcumin, troglitazone, salvianolic acid B or GW9662. The effect on HSCs
      proliferation was determined by MTT colorimetry. Total RNA was extracted by
      TRizol reagent and gene levels were determined by semi-quantitative RT-PCR. Total
      cellular and nuclear protein were isolated and separated by 10% sodium dodecy
      lsulfate polyacrylamide gel electrophoresis. Protein levels were determined by
      Western blot. Cell apoptosis was detected by Hoechst 33258 staining. PPARgamma
      subcellular distribution was detected by immunofluorescent staining. The
      activities of MMP-2 and 9 were measured by Gelatin zymograph assay. RESULTS:
      Curcumin suppressed HSCs proliferation in a dose-dependent manner. As HSCs
      underwent gradual activation with culture prolongation the PPARgamma nuclear
      expression level decreased. Curcumin up-regulated PPARgamma expression and
      significantly inhibited the production of alpha-SMA and collagen I. PPARgamma is
      expressed in the cytoplasm and nucleus and is evenly distributed in HSCs, but
      accumulated in the nucleus of HSCs and disappeared from cytoplasm after curcumin
      treatment. Hoechst 33258 staining showed that curcumin induced the apoptosis of
      culture-activated HSCs and significantly increased pro-apoptotic Bax expression
      and reduced anti-apoptotic Bcl-2 expression. Cyclin D1 gene, activated NFkappaB
      p65 protein and TGFbetaR-I protein expression were down-regulated significantly
      by curcumin. The activities of MMP-2 and MMP-9 were enhanced significantly by
      curcumin. CONCLUSIONS: Curcumin can inhibit the proliferation and activation of
      HSCs, induce the apoptosis of activated HSCs and enhance the activities of MMP-2
      and MMP-9. The effects of curcumin are mediated through activating the PPARgamma
      signal transduction pathway and associated with PPARgamma nuclear
      translocation/redistribution.

PMID- 17531122
TI  - Berbamine selectively induces apoptosis of human acute promyelocytic leukemia
      cells via survivin-mediated pathway.
AB  - BACKGROUND: Currently, resistance and relapse are still major problems in acute
      promyelocytic leukemia (APL) cases. Thus, new agents that override the resistance
      are crucial to the development of curative therapies for APL. In this study, we
      investigated the effects of berbamine on the proliferation of APL cell line NB4
      and its possible mechanisms. METHODS: NB4 cells were treated with berbamine at
      different concentrations (0-64 microg/ml) for 72 hours. MTT assay was used to
      determine proliferation inhibition of NB4 cells. Cell apoptosis was evaluated by
      both flow cytometry (FCM) and morphological examination. PML/RAR-alpha and
      survivin mRNAs were measured by nested-RT-PCR and RT-PCR, respectively. Activated
      caspase 3 was determined by FCM. RESULTS: Berbamine greatly inhibited the
      proliferation of NB4 cells in dose- and time-dependent manners, and its IC50
      value was 3.86 microg/ml at 48 hours. Both morphological observations and FCM
      results showed that berbamine induced apoptosis of NB4 cells with concomitant
      increase of activated caspase-3 and decrease of survivin mRNA. After treatment
      with berbamine at 8 microg/ml for 48 hours, the percentage of apoptotic cells
      increased from 2.83% to 58.44% (P<0.01), and the percentage of cells with
      activated-caspase 3 elevated from 2.06% to 70.89% (P<0.01), whereas, level of
      survivin mRNA was reduced to 38.24% of control (P<0.01). However, no significant
      change was observed in PML/RAR-alpha mRNA. CONCLUSIONS: Berbamine induces caspase
      3-dependent apoptosis of leukemia NB4 cells via survivin-mediated pathway,
      suggesting that berbamine may be a novel potential agent against APL with a
      mechanism distinct from that of all-trans retinoic acid (ATRA) and arsenic
      trioxide (ATO).

PMID- 17531123
TI  - Genome-wide expression profiling of the response to terbinafine in Candida
      albicans using a cDNA microarray analysis.
AB  - BACKGROUND: Candida albicans is the most frequently seen opportunistic human
      fungal pathogen. Terbinafine is an allylamine antifungal agent that has been
      proven to have high clinical efficacy in the therapy of fungal infections, the
      mechanism of action of terbinafine involves the specific inhibition of fungal
      squalene epoxidase, resulting in ergosterol deficiency and accumulation of
      intracellular squalene. We used cDNA microarray analysis technology to monitor
      global expression profile changes of Candida albicans genes in response to
      terbinafine treatment, and we anticipated a panoramic view of the responses of
      Candida albicans cells to the representatives of allylamine antifungal agents at
      the molecular level in an effort to identify drug class-specific and mechanism
      independent changes in gene expression. METHODS: Candida albicans strain ATCC
      90028 was exposed to either medium alone or terbinafine at a concentration
      equivalent to the 1/2 minimal inhibitory concentrations (MICs, 4 mg/L) for 90
      minutes. RNA was isolated and gene expression profiles were compared to identify
      the changes in the gene expression profile using a cDNA microarray analysis.
      Differential expression of 10 select genes detected by cDNA microarray analysis
      was confirmed by semi-quantitative reverse transcription-polymerase chain
      reaction (RT-PCR). RESULTS: A total of 222 genes were found to be responsive to
      terbinafine, including 121 up-regulated genes and 101 down-regulated genes. These
      included genes encoding membrane transport proteins belonging to the members of
      the ATP-binding cassette (ABC) or major facilitator superfamily (MFS; CDR1, AGP2,
      GAP6, PHO84, HOL3, FCY23, VCX1), genes involved in stress response and
      detoxification (CDR1, AGP2, HOL3), and gene involved in the ergosterol
      biosynthesis pathway (ERG12). The results of semi-quantitative RT-PCR were
      consistent with that of the cDNA microarray analysis. CONCLUSIONS: The up
      regulation of the gene encoding the multidrug resistance efflux pump CDR1 may
      contribute to the terbinafine resistance in Candida albicans. However, the
      precise roles of other affected genes remain unclear, further studies of these
      genes and their respective products that play roles in the context of antifungal
      resistance are warranted.

PMID- 17531124
TI  - Molecular characteristics of rifampin and isoniazid resistant Mycobacterium
      tuberculosis strains from Beijing, China.
AB  - BACKGROUND: China is one of the high burden countries of Mycobacterium
      tuberculosis (TB) infection globally, with high incidence and mortality. We
      studied the molecular characteristics of rifampin (RIF) and isoniazid (INH)
      resistant Mycobacterium tuberculosis strains from Beijing, China, in order to
      find out the genetic marker for rapid detection of specific drug resistance.
      METHODS: Forty pansusceptible and 81 resistant strains of Mycobacterium
      tuberculosis isolated from Beijing, China during 2002-2005 were analyzed. The
      modified rifampin oligonucleotide (RIFO) assay based on reverse line blot
      hybridization was used to detect mutations in the 81 bp hot-spot region of rpoB
      gene, which is associated with RIF resistance. The INH resistance associated
      genes, regulatory region mab-inhA (-15C/T) and structural gene katG S315T were
      detected by reverse line blot hybridization and PCR-restriction fragment length
      polymorphism (RFLP) method respectively. All the strains were typed by
      spoligotying and the Beijing genotype was further subdivided by NTF locus
      analysis. The distribution of drug resistance associated mutations in the above
      genes was compared in these groups. RESULTS: Sixty-five (91.5%) of 71 RIF
      resistant and 52 (92.9%) of 56 multidrug-resistant (MDR, i.e. resistant to at
      least RIF and INH) strains were found to harbor mutations in the rpoB hot-spot
      region. No mutation was detected in RIF sensitive strains. The specificity and
      sensitivity of the modified RIFO assay were 100% and 91.5%, respectively. katG315
      AGC>ACC and inhA-15C>T mutations were found in 40 (60.6%) and 10 (15.2%) of 66
      INH resistant strains, respectively; 7.6% of INH-resistant strains had mutations
      in both of these genes. Therefore, a combined use of both katG315 and inhA-15
      identified 68.2% of INH-resistant strains. The Beijing genotype accounted for
      91.7% of total strains and was further subdivided into "modern" (76.6%) and
      "ancestral" (23.4%) group. There is no significant difference between "ancestral"
      and "modern" group in prevalance of drug resistance-associated gene mutations.
      CONCLUSIONS: The hot-spot region of rpoB gene can be used as genetic marker for
      detection of RIF resistant strains; a combined use of both katG315 and inhA-15
      can improve the detection rate of INH resistant strains; the Beijing genotype is
      prevalent in Beijing, China; the modified RIFO assay can be a practical tool for
      rapid detection of RIF resistant and MDR isolates in the routine diagnostic work.

PMID- 17531125
TI  - A missense mutation S228P in the CRYBB1 gene causes autosomal dominant congenital
      cataract.
AB  - BACKGROUND: Congenital cataract is a highly heterogeneous disorder at both the
      genetic and phenotypic levels. This study was conducted to identify disease locus
      for autosomal dominant congenital cataracts in a four generation Chinese family.
      METHODS: Family history and clinical data were recorded. All the members were
      genotyped with microsatellite markers which are close to the known genetic loci
      for autosomal congenital cataracts. Two-point Lod scores were obtained using the
      MLINK of the LINKAGE program package (ver 5.1). Candidate genes were amplified by
      polymerase chain reaction (PCR) and direct cycle sequencing. RESULTS: The maximum
      Lod score of Zmax-2.11 was obtained with three microsatellite markers D22S258,
      D22S315, and D22S1163 at recombination fraction theta=0. Haplotype analysis
      showed that the disease gene was localized to a 18.5 Mbp region on chromosome 22
      flanked by markers D22S1174 and D22S270, spanning the beta-crystallin gene
      cluster. A c.752T-->C mutation in exon 6 of CRYBB1 gene, which resulted in a
      heterozygous S228P mutation in predicted protein, was found to cosegregate with
      cataract in the family. CONCLUSIONS: This study identified a novel mutation in
      CRYBB1 gene in a Chinese family with autosomal dominant congenital cataract.
      These results provide strong evidence that CRYBB1 is a pathogenic gene for
      congenital cataract.

PMID- 17531126
TI  - Nucleotide sequence characterization and phylogenetic analysis of hantaviruses
      isolated in Shandong Province, China.
AB  - BACKGROUND: China is the most severe endemic area of hemorrhagic fever with renal
      syndrome (HFRS) in the world with 30,000-50,000 cases reported annually, which
      accounts for more than 90% of total number of cases worldwide. The incidence rate
      of the syndrome in Shandong Province is one of the highest in China, which has
      ever reached 50 per 100,000 persons per year. However, the molecular
      characteristics of hantaviruses (HV) epidemic in Shandong Province remain
      unclear. Therefore it is useful to clarify nucleotide sequence and phylogenetic
      characteristics of HV isolated in Shandong Province in order to provide better
      advices to control and prevent HFRS. METHODS: RNAs were extracted from sera of
      clinically diagnosed patients and positive rodent lungs that were detected by
      indirect immunofluorescent assay (IFA). Partial M segments of HV were amplified
      from the RNAs with reverse transcription nested polymerase chain reactions
      (nested PCR) using hantavirus genotype specific primers. The nested PCR products
      were sequenced and compared with those from previously epidemic isolates in
      Shandong and with other representative HV sequences from GenBank. Phylogenetic
      tree analyses were performed based on the sequences of the M genes. RESULTS:
      Thirty-four HV isolates in Shandong showed 67.1%-100% nucleotide identities. The
      nucleotide homologies among 6 Hantaan viruses (HTNV) isolates in Shandong were
      78.1%-98.7%, while the homologies among 28 Seoul virus (SEOV) isolates in
      Shandong were 93.7%-100%. There were at least 3 subtypes HTNV (H2, H5, H9) and 2
      subtypes SEOV (S2, S3) in Shandong Province. CONCLUSIONS: In Shandong Province,
      the homologies of HTNV were lower and there were no predominant subtypes, while
      the homologies of SEOV were higher and S3 was the predominant subtype. The
      homologies of SEOV from rodents were higher than those from patients. The
      distribution of subtypes in Shandong was similar to that of the adjoining
      provinces. Phylogenetic analyses of the sequences showed geographic clustering of
      HV in Shandong.

PMID- 17531127
TI  - Full-length clone and characterization of a human immunodeficiency virus type 1
      subtype B' isolated from Hubei Province, China.

PMID- 17531128
TI  - A SPG3A mutation with a novel foot phenotype of hereditary spastic paraplegia in
      a Chinese Han family.

PMID- 17531129
TI  - Abnormality of chromosome 8 in desmoid-type fibromatosis.

PMID- 17531130
TI  - Post-transplant lymphoproliferative disorder treated with rituximab: case report.

PMID- 17531131
TI  - Primitive neuroectodermal tumor of lumbar spine: case report.

PMID- 17531132
TI  - Idiopathic airway-centered interstitial fibrosis: report of two cases.

PMID- 17531133
TI  - Acro-dermato-ungual-lacrimal-tooth syndrome: case report.

PMID- 17531134
TI  - Tuberous sclerosis complex complicated with extraventricular cystic giant cell
      astrocytoma: case report.

PMID- 17531135
TI  - Interventional therapy procedures assisted by medical imaging and simulation. The
      experience of U 703 Inserm (Lille France).
AB  - Since the early 1990s, minimally invasive techniques have been increasingly used
      in ever more and diversified fields of application. These techniques have some
      shared characteristics (predominant role of medical imaging, intensive use of new
      communication technologies, a multidisciplinary medical and scientific framework,
      etc.) but also shared specific problems (high-tech tools unfamiliar to the
      medical users, a major and long period of time for technological development,
      unavailability of training systems, difficulties in obtaining regulatory
      approval). For a long time, our Laboratory of Medical Physics (U 703 Inserm) has
      developed an innovative research activity in biomedical engineering in the field
      of assisted therapy, medical imaging and medical simulation. This paper presents
      the general context of interventional therapy procedures assisted by image and
      simulation and describes our scientific activities based on realistic objectives
      close to medical practice.

PMID- 17531136
TI  - Parameter estimation and order selection for an empirical model of VO2 on
      kinetics.
AB  - In humans, VO2 on-kinetics are noisy numerical signals that reflect the pulmonary
      oxygen exchange kinetics at the onset of exercise. They are empirically modelled
      as a sum of an offset and delayed exponentials. The number of delayed
      exponentials; i.e. the order of the model, is commonly supposed to be 1 for low
      intensity exercises and 2 for high-intensity exercises. As no ground truth has
      ever been provided to validate these postulates, physiologists still need
      statistical methods to verify their hypothesis about the number of exponentials
      of the VO2 on-kinetics especially in the case of high-intensity exercises. Our
      objectives are first to develop accurate methods for estimating the parameters of
      the model at a fixed order, and then, to propose statistical tests for selecting
      the appropriate order. In this paper, we provide, on simulated Data, performances
      of Simulated Annealing for estimating model parameters and performances of
      Information Criteria for selecting the order. These simulated Data are generated
      with both single-exponential and double-exponential models, and noised by white
      and Gaussian noise. The performances are given at various Signal to Noise Ratio
      (SNR). Considering parameter estimation, results show that the confidences of
      estimated parameters are improved by increasing the SNR of the response to be
      fitted. Considering model selection, results show that Information Criteria are
      adapted statistical criteria to select the number of exponentials.

PMID- 17531137
TI  - Application of mathematical morphology to the quantification of in vitro
      endothelial cell organization into tubular-like structures.
AB  - Experiments of in vitro angiogenesis are important tools for studying both the
      mechanisms of formation of new blood vessels and the potential development of
      therapeutic strategies to modulate neovascularisation (e.g., screening of new
      pharmacological molecules). One of the most frequently used angiogenesis assays
      is the culture of endothelial cells on a reconstituted basement membrane named
      Matrigel, since the cells constitute a capillary-like network which can be
      quantified by image analysis. In this paper, a global, robust and fully automated
      methodology is proposed to segment and quantify in vitro endothelial cell
      networks from greyscale images using mathematical morphology operators. After
      extracting the established cell network by means of a top-hat transformation and
      separating the tubular structures and the cell aggregates by size and shape an
      interpolation algorithm yields a reconstituted closed network. Using these image
      data results different kinds of quantitative parameters are calculated:
      size/shape, morphological distribution, spatial organisation, etc. In this paper,
      we have established an automatic quantitative analysis to evaluate a modulator
      effect of a sulphated exopolysaccharide on FGF-2-induced in vitro angiogenesis,
      according to different parameters. Experimental results allow us to draw a
      discussion of the pertinence of the alternative morphological parameters to
      evaluate the characteristics and behaviour of cell cultures.

PMID- 17531138
TI  - Structural analysis and application to brain imaging.
AB  - Our goal is to organize the ElectroEncephaloGram (EEG) signal so as to describe
      and image various brain activities. Our work is based on a data structure, a
      graph, which sums up the brain activity in the spatial, temporal and frequency
      domains. From the information contained in the time-frequency map of EEG signals,
      a graph is constructed. In order to analyze the complexity of the signal, our
      method is based on a multi-scale approach with several levels of information
      extraction. To compare different EEG signals, we use techniques of graph-matching
      with our data structure. The developed algorithm is based on the A* algorithm
      that allows us to compare variations of the recorded EEG in term o f latency,
      frequency, energy and activated areas. The results of this project show first,
      that the graph is an appropriate tool to reduce the cortical activity complexity,
      and second, that graph-matching offers some interesting perspectives in order to
      describe functional brain activity.

PMID- 17531139
TI  - An automatic image analysis approach to quantify stained cell cultures.
AB  - Counting cells in culture is a common task in biotechnology research and
      production. This process should be automated to provide fast and objective
      quantification. Flow cytometry is adapted to count cells in suspension. However,
      the morphological information and the spatial organisation of adherent cells are
      lost when cells are removed from culture. This paper proposes a methodology based
      on image analysis to quantify stained nuclei in culture. The protocol is composed
      of several steps: cell staining, automatic microscopy imaging, segmentation by an
      automatic algorithm including a classification approach, and computation of
      quantitative data that characterizes the growth of cells. An evaluation shows
      that the automatic process of counting provides results similar to human manual
      counting. The major interests of the proposed approach are the fully automated
      processing and preservation of cell shapes and positions in culture. More than
      two thousand culture conditions have been measured by this tool for various
      applications including optimization of cell culture media, improvement of the
      culture processes and measurement of drug toxicity.

PMID- 17531140
TI  - A fast and efficient segmentation scheme for cell microscopic image.
AB  - Microscopic cellular image segmentation schemes must be efficient for reliable
      analysis and fast to process huge quantity of images. Recent studies have focused
      on improving segmentation quality. Several segmentation schemes have good quality
      but processing time is too expensive to deal with a great number of images per
      day. For segmentation schemes based on pixel classification, the classifier
      design is crucial since it is the one which requires most of the processing time
      necessary to segment an image. The main contribution of this work is focused on
      how to reduce the complexity of decision functions produced by support vector
      machines (SVM) while preserving recognition rate. Vector quantization is used in
      order to reduce the inherent redundancy present in huge pixel databases (i.e.
      images with expert pixel segmentation). Hybrid color space design is also used in
      order to improve data set size reduction rate and recognition rate. A new
      decision function quality criterion is defined to select good trade-off between
      recognition rate and processing time of pixel decision function. The first
      results of this study show that fast and efficient pixel classification with SVM
      is possible. Moreover posterior class pixel probability estimation is easy to
      compute with Platt method. Then a new segmentation scheme using probabilistic
      pixel classification has been developed. This one has several free parameters and
      an automatic selection must dealt with, but criteria for evaluate segmentation
      quality are not well adapted for cell segmentation, especially when comparison
      with expert pixel segmentation must be achieved. Another important contribution
      in this paper is the definition of a new quality criterion for evaluation of cell
      segmentation. The results presented here show that the selection of free
      parameters of the segmentation scheme by optimisation of the new quality cell
      segmentation criterion produces efficient cell segmentation.

PMID- 17531141
TI  - Algorithms for the extraction of various diameter vessels.
AB  - In this communication we propose a new and automatic strategy for the multi-scale
      extraction of vessels. The objective is to obtain a good representation of the
      vessels. That is to say a precise characterization of their centerlines and
      diameters. The adopted solution requires the generation of an image scale-space
      in which the various levels of details allow to process arteries of any diameter.
      The proposed method is implemented using the Partial Differential Equations (PDE)
      and differential geometry formalisms. The differential geometry allows, by the
      computation of a new valley response, to characterize the centerlines of vessels
      as well as the bottom lines of the valleys of the image surface. The information
      given by the centerlines and valley response at different scales are used to
      obtain the 2D multi-scale centerlines of the arteries. To that purpose, we
      construct a multi-scale adjacency graph which permits to keep the K strongest
      detections. Then, the detection we obtain is coded as an attributed graph. The
      suggested algorithm is applied in the scope of two kinds of angiograms:
      coronaries and retinal angiograms.

PMID- 17531143
TI  - High prevalence of human polyomavirus JC VP1 gene sequences in pediatric
      malignancies.
AB  - The oncogenic potential of human polyomavirus JC (JCV), a ubiquitous virus that
      establishes infection during early childhood in approximately 70% of the human
      population, is unclear. As a neurotropic virus, JCV has been implicated in
      pediatric central nervous system tumors and has been suggested to be a pathogenic
      agent in pediatric acute lymphoblastic leukemia. Recent studies have demonstrated
      JCV gene sequences in pediatric medulloblastomas and among patients with
      colorectal cancer. JCV early protein T-antigen (TAg) can form complexes with
      cellular regulatory proteins and thus may play a role in tumorigenesis. Since JCV
      is detected in B-lymphocytes, a retrospective analysis of pediatric B-cell and
      non-B-cell malignancies as well as other HIV-associated pediatric malignancies
      was conducted for the presence of JCV gene sequences. DNA was extracted from 49
      pediatric malignancies, including Hodgkin disease, non-Hodgkin lymphoma, large
      cell lymphoma and sarcoma. Polymerase chain reaction (PCR) was conducted using
      JCV specific nested primer sets for the transcriptional control region (TCR),
      TAg, and viral capsid protein 1 (VP1) genes. Southern blot analysis and DNA
      sequencing were used to confirm specificity of the amplicons. A 215-bp region of
      the JCV VP1 gene was amplified from 26 (53%) pediatric tumor tissues. The JCV TCR
      and two JCV gene regions were amplified from a leiomyosarcoma specimen from an
      HIV-infected patient. The leiomyosarcoma specimen from the cecum harbored the
      archetype strain of JCV. Including the leiomyosarcoma specimen, three of five
      specimens sequenced were typed as JCV genotype 2. The failure to amplify JCV TCR,
      and TAg gene sequences in the presence of JCV VP1 gene sequence is surprising.
      Even though JCV TAg gene, which is similar to the SV40 TAg gene, is oncogenic in
      animal models, the presence of JCV gene sequences in pediatric malignancies does
      not prove causality. In light of the available data on the presence of JCV in
      normal and cancerous colon epithelial tissue and our data on amplification of JCV
      from the cecum of an HIV-infected pediatric patient, further studies are
      warranted on the role of colon epithelium in the pathogenesis of JCV infection.

PMID- 17531144
TI  - Inhibition of DNA topoisomerase I and growth inhibition of human cancer cell
      lines by an oleanane from Junellia aspera (Verbenaceae).
AB  - DNA topoisomerases and DNA polymerases are enzymes that play a crucial role in
      DNA metabolism events such as replication, transcription, recombination, and
      chromosome segregation during mitosis. Thus, DNA topoisomerases and DNA
      polymerases inhibitors could be expected to have antitumor effects. Naturally
      occurring triterpenoids isolated from Junellia aspera (Gillies & Hook; Moldenke)
      (Verbenaceae) were assayed for human DNA topoisomerase I and Taq DNA polymerase
      inhibitory activities. Maslinic acid (2) and its diacetyl derivative (7) showed
      human DNA topoisomerase I inhibitory activity with IC50 values in the range of 76
      80 microM and growth inhibition against various human solid tumour cell lines
      with GI50 values in the range of 5-18 microM. The triterpene frames could be used
      for screening new inhibitors of the enzyme, and computer-simulated drug design
      using the frame and pocket structure of enzyme may in theory be a possible
      approach to develop new inhibitors.

PMID- 17531145
TI  - Sequential combination chemotherapy in human breast cancer: a basis for increased
      antineoplastic activity and bone marrow protection.
AB  - These studies were designed to develop procedures that would capitalize on the
      growth inhibitory effects of tamoxifen (Tam) and methotrexate (MTX) in breast
      cancer, while protecting bone marrow with a priming dose of 5-fluorouracil (5
      FU). High-dose MTX (10 microM) cytotoxicity is maintained in MCF-7 breast cancer
      cells but reduced in human bone marrow by a priming and nontoxic dose of 5-FU (10
      microM). MTX cytotoxicity is decreased in MCF-7 breast cancer cells when the
      selective estrogen receptor modulator (SERM) Tam (10 microM) is administered 24
      hours prior to 5-FU (10 microM) followed two hours later by MTX (early Tam)
      resulting in a growth rate of 57.42 +/- 4.38% of the control rate. However, when
      breast cancer cells are exposed to Tam 24 hours after 5-FU + MTX (late Tam), the
      interaction between MTX and Tam is not antagonistic, the percentage of the
      control is 29.47 +/- 4.54%. Bone marrow exposure to these drug combinations
      exhibits a protective effect to the MTX cytotoxicity, with the early Tam
      combination yielding 59.45 +/- 16.38% of the control for MTX alone. These studies
      suggest that a) Tam in combination with a priming dose of 5-FU protects bone
      marrow from MTX cytotoxicity, b) the interactions between Tam and MTX are
      sequence-dependent, c) Tam decreases the effect of MTX when Tam administration
      precedes MTX.

PMID- 17531146
TI  - Internalization of near-infrared fluorescent dyes within isolated macrophage
      populations.
AB  - The development and application of microsensor technology has enhanced the
      ability of scientists to further understand various biological activities, such
      as changes in the intracellular environment after injury or toxic exposure. NIR
      microsensor technology may be useful in detecting the cellular injuries or
      adverse changes during the early onset period, allowing for the administration of
      therapies to initiate recovery. The development and use of Infrared (IR) and near
      infrared (NIR) dyes as biological micro-sensors due to their advanced spectral
      characteristics may be helpful. Three of the more useful NIR dye characteristics
      include the ability to minimize background interference by extraneous biological
      matrices, the ability to exhibit optimal molar absorptivity and quantum yields,
      and the ability to maintain normal cellular activity. Thus, the current study was
      designed to investigate the ability of selected NIR micro-sensor dyes to undergo
      cellular internalization, demonstrate intracellular NIR fluorescent signaling,
      and maintain normal cellular activity. The results demonstrate that the selected
      NIR micro-sensor dyes undergo cellular internalization. The presence of the dyes
      within the cells did not affect cell viability. In addition, these dyes
      demonstrate changes in absorbance and fluorescence after the immune cells were
      challenged with a stimulant. Moreover, critical cellular functions, such as tumor
      necrosis factor release and superoxide production were not compromised by the
      internalization of the fluorescent dyes. These data suggest that selected NIR
      micro-sensor dyes can undergo intracellular internalization within isolated
      macrophages without adversely affecting various parameters of normal cellular
      activity.

PMID- 17531147
TI  - Effect of Cnidoscolus aconitifolius leaf extract on the blood glucose and insulin
      levels of inbred type 2 diabetic mice.
AB  - The effects of Cnidoscolus aconitifolius (CA) leaf extract and chlorpropamide on
      blood glucose and insulin levels in the inbred type 2 diabetic mice are reported.
      After treatment with CA, the glucose levels were measured at 0 and 2-hour
      intervals in experimental groups and controls. Group I received no treatment and
      served as control; Group II was the reference and it received chlorpropamide;
      Groups I-III were moderately diabetic, 100-300 mg/dL blood glucose levels while
      Group IV were severely diabetic (> 300 mg/dL). Groups III and IV received CA and
      served as test groups. There was no significant difference between the blood
      glucose levels at 0 and 2 hours for the control group, (P>0.23) but there were
      statistically significant differences for Group II (P<0.0002); Group III
      (P<0.002) and Group IV (P<0.0001). For moderately diabetic mice, CA and
      chlorpropamide decreased the glucose levels by 25.6% and 16.3% respectively while
      for the severely diabetic mice CA decreased the blood glucose by 43.7%. It is
      proposed that CA has an insulinogenic property that possibly stimulated dormant
      beta-cells to secrete insulin. The histopathology of several organs in the
      treated animals was found to differ from the expected. The islets of Langerhans
      for example were found to be preserved in the time frame examined. Also the liver
      and kidney were found to display milder pathology in the treated groups.

PMID- 17531148
TI  - Mathematical models for conventional and microwave thermal deactivation of
      Enterococcus faecalis, Staphylococcus aureus and Escherichia coli.
AB  - Temperature dependencies of survival fecal coliforms such as Enterococcus
      faecalis, Staphylococcus aureus and Escherichia coli in water were investigated
      between 25-65 degrees C. Measured dependencies had "bell" shaped form with
      maximum bacterial viability at 35-45 degrees C. The rates of growth and decay of
      bacterial viability depend on specific forms of bacteria. At temperatures of 60
      65 degrees C the number of viable bacteria decreased in one hundred times in
      comparison with the maximum value. Similar "bell" shape forms were found for
      dependencies between bacterial viability and time of microwave (dielectric)
      heating of water. The dependencies had maximum value at 1-2 min of microwave
      heating. Then, the number of viable bacteria decreased, and at 4-5 min of
      microwave heating, became insignificantly small. The proposed mathematical models
      for conventional and microwave heating took into account "growth" and "death"
      factors of bacteria, and had forms of second degree polynomial functions. The
      results showed good relationships (with coefficient correlation 0.84-0.99)
      between the proposed mathematical models and experimental data for both
      conventional and microwave heating.

PMID- 17531149
TI  - Mathematical model of manganese ion catalyzed microwave deactivation of
      Enterococcus faecalis, Staphylococcus aureus and Escherichia coli.
AB  - Enterococcus faecalis, Staphylococcus aureus and Escherichia coli survival was
      investigated using microwave irradiation (power 130 W) both in a water control
      and in the presence of a 1 microM manganese ion solution. Measured survival
      dependencies had "bell" shape form with maximum bacterial viability between 1-2
      min of microwave heating. Additional heating revealed bacteria survival
      decreasing up to 3 min of microwave heating when viability became insignificantly
      small. The total deactivation time of bacteria in the presence of manganese ions
      was significantly smaller then that of bacteria irradiated in the microwave
      without manganese ions present (4-5 min). One possible explanation for the rapid
      reduction of bacterial survival during microwave irradiation in the presence of
      manganese ions is that increasing manganese ion penetration into bacteria along
      with microwave irradiation related to an increase of kinetic energy of ions, and
      damaging of bacteria by metal ions. The proposed mathematical model for microwave
      heating took into account "growth" and "death" factors of bacteria. It assumes
      that rates of bacterial growth and decay are linear functions of water
      temperature, and rate of bacterial decay that relates with metal concentration
      into water is also linear, which influenced the differential equation for the
      dependence between number of survival bacteria and temperature water. By using
      proportionality between the time of microwave heating and water temperature we
      derived the differential equation, between bacterial viability and time of
      microwave irradiation which was used as mathematical model for microwave heating
      in the presence of metal ions. This model had forms of second-degree polynomial
      functions. We received good relationships (with coefficient of correlation 0.92
      0.99) between proposed mathematical model and experimental data for all bacterial
      deactivation.

PMID- 17531150
TI  - Requirement of protein kinase type I for cAMP-mediated up-regulation of lipid
      linked oligosaccharide for asparagine-linked protein glycosylation.
AB  - Glycan chains of asparagine-linked (N-linked) glycoproteins play a significant
      role in protein structure and function, as well as in angiogenesis an essential
      process for breast or other solid tumor growth. Non-availability of these chains
      causes incorrect folding of glycoproteins and leads to programmed cell death
      (i.e., apoptosis) through unfolded protein response (UPR) signaling. Cells
      actively processing cAMP signals modulate the glycan chain biosynthesis by PKA.
      Glycosylation of cellular proteins in a PKA type I-deficient CHO mutant 10248 was
      much reduced when compared with the wild type CHO 10001. The rate of LLO
      biosynthesis is similar in both cell types but quantitatively it is low in the
      mutant. Pulse-chase experiments indicated that the t(1/2) for LLO-turnover in CHO
      10248 was twice as high as that of the wild type. This correlated with the
      reduced DPMS activity. The Km for GDP-mannose for the DPMS activity was 3-4 folds
      higher in the mutant than that of the wild type with or without exogenously added
      Dol-P. The kcat of DPMS was also reduced in the mutant. In vitro phosphorylation
      of microsomes from the CHO 10248 by PKA, on the other hand, restored the DPMS
      activity to the normal level. The LLO biosynthesis also improved significantly in
      MR1, a revertant of the CHO 10248. The turnover of LLO in MR1 and the
      glycoprotein profile were also at par with the wild type. Therefore, we conclude
      that PKA type I plays an important role in modulating the protein N-glycosylation
      in cAMP responsive cells.

PMID- 17531151
TI  - In vitro reconstitution of legumin (11S) mRNA and binding proteins as related to
      post-transcriptional regulation of protein synthesis in developing alfalfa
      embryos.
AB  - There is undetectable transcription of 11S storage protein (medicagin) mRNA by
      nuclei isolated from pre-cotyledonary-stage somatic embryos of alfalfa (Medicago
      sativa L). However, this message exists at steady-state levels in the embryos at
      this stage of development without concomitant synthesis of the storage protein.
      At the pre-cotyledonary stage, therefore, the transcriptional rate for 11S mRNA
      is low; what message is transcribed is sequestered in the form of mRNP complexes
      and is not recruited into polysomes in vivo (33). Both transcription (in vivo and
      in isolated nuclei) and translation of the 11S mRNA are evident at the onset of
      cotyledon development in somatic and zygotic embryos, reaching a maximum during
      expansion of the cotyledons and then declining as the embryos mature. Pre
      cotyledonary-stage somatic embryos which do not utilize the 11S-mRNA in polysomes
      lack certain mRNA-binding proteins (32, 36 and 38 kD) which are present at later
      stages of development. These mRNA-binding proteins may be responsible for the
      initiation of large polysome formation since they were exclusively present in the
      translational extracts of cotyledonary somatic and zygotic embryos in which there
      was no repression of storage protein synthesis. In contrast, the pre-cotyledonary
      somatic embryos contained a different set of 11S-mRNA-binding proteins (28, 50,
      55, and 62 kD) whose presence in the cotyledonary stage embryos was very rare or
      non-existent; these could be responsible for preventing translation.

PMID- 17531152
TI  - Cloning and expression of streptomycin inactivating enzymes APH(6)-Ia and APH(6)
      Id.
AB  - Discovered in the 1940s by Selman Waksman, the aminoglycoside antibiotic
      streptomycin is clinically important in the treatment of tuberculosis worldwide.
      However, strains of Mycobacterium tuberculosis and other pathogenic bacteria have
      become resistant to streptomycin. One mechanism by which this can occur is
      through the action of phosphotransferases that attach a phosphate group to
      position 6 of the streptidine ring of streptomycin, thereby inactivating it. Two
      such phosphotransferases are APH(6)-Ia from producer strain Streptomyces griseus,
      and APH(6)-Id found in animal, plant and human pathogenic isolates. Here, we
      report the subcloning and expression in Escherichia coli of soluble recombinant
      APH(6)-Ia and Id enzymes. Sequencing of aph(6)-Ia revealed a one-nucleotide
      disagreement with the published sequence, such that the amino acid at position
      262 is an alanine instead of a serine. The sequence of aph(6)-Id is identical to
      that of the gene found in transposon Tn5393 of plant pathogen Erwinia amylovora.
      The successful expression of soluble forms of these enzymes now paves the way for
      experiments to study their structure and function by using site-directed
      mutagenesis.

PMID- 17531154
TI  - Research centers on minority institutions (RCMI): II.
AB  - The goal of the Research Centers in Minority Institutions (RCMI) is to develop
      biomedical and behavioral research at institutions with 50% minority enrollment
      (African Americans, Hispanics, Native Hawaiians, Pacific Islanders, Native
      Americans and Alaska Natives) who have been underrepresented in the biomedical
      sciences. The program has made available resources vital to scientific
      development and progress. While these resources have included, equipment,
      personnel supplies, Core laboratories etc, important effective approaches to
      research also have been emerging.

PMID- 17531155
TI  - Prevalence of melanocortin system transcripts in rat salt homeostasis endocrine
      tissues.
AB  - Melanocortin receptors have been implicated in the confounding factors of
      cardiovascular diseases such as obesity, insulin resistance and salt-sensitive
      hypertension. The aim of this study was determine how increased dietary salt
      intake affects the expression profiles of melanocortin system genes in relevant
      endocrine tissues. Total RNA was isolated from the pituitary and adrenal glands
      of Wistar Kyoto (WKY) and stroke-prone spontaneously hypertensive rats (SP-SHR)
      and subjected to real-time PCR analysis. Expression levels of pro
      opiomelanocortin (POMC), POMC processing enzymes prohormone convertases 1 and 2
      (PC1/PC2), melanocortin 3 receptor (MC3R) and melanocortin 5 receptor (MC5R) were
      not significantly affected by high dietary salt intake in either WKY or SP-SHR
      tissues. Consistent with known endocrine relationship between the pituitary and
      adrenal glands, the expression levels of the ACTH receptor, MC2R, were five
      orders of magnitude higher in adrenal tissues whereas those of POMC were three
      orders of magnitude higher in the pituitary. MC3R, PC1 and PC2 transcripts were
      expressed at similar levels in both tissues while MC5R was expressed at a higher
      level in the adrenal tissues. These results are therefore inconsistent with an
      endocrine pathway that involves pituitary derived gamma-MSH modulating adrenal
      function in response to high dietary salt intake.

PMID- 17531156
TI  - Methamphetamine-induced locomotor activity and behavioral sensitization: are
      dopamine d3 receptors involved?
AB  - Drug sensitization is a behavioral phenomenon that occurs following repeated
      administration of methamphetamine (METH) and similar CNS stimulants. The
      mechanism of drug sensitization is unknown, but is believed to be due to
      downregulation of dopamine D3 receptors. It is hypothesized that repeated
      administration of dopamine D3 agonists results in downregulation of D3 receptors
      in methamphetamine-induced (METH-IND) sensitization. Furthermore, repeated
      administration of dopamine D3 antagonists and METH cause upregulation of D3
      receptors and block METH-IND sensitization. The objective of this study was to
      determine the role of D3 receptors in METH-IND sensitization. To test these
      hypotheses, male mice received chronic injections (i.p.) of 2 mg/kg of the
      dopamine D3 agonist, PD128907 plus 0.5 mg/kg of METH or 8 mg/kg of D3 antagonist,
      U99194A and 0.5 mg?kg of METH daily for 7-days. Drugs were withdrawn on day 8,
      and METH-IND sensitization was determined on day 18. Locomotor activity was
      measured for 75 minutes immediately after METH administration in an activity
      monitor. Acute administration of PD128907 decreased METH-IND locomotion, p < 0.
      01, and acute U99194A increased it. However, chronic administration of these
      drugs did not alter the locomotor effects of METH (p > 0.05). These findings
      support in-part the hypothesis that dopamine D3 receptors are downregulated in
      METH-IND sensitization.

PMID- 17531157
TI  - Differential enrichment of simple sequence repeats in selected Alzheimer
      associated genes.
AB  - The involvement of beta-amyloid (Abeta) in the pathogenesis of Alzheimer's
      disease (AD) has been well documented. In addition, a significant degree of
      information has been documented regarding the genetics of Abeta production and
      aggregation in familial forms of AD (FADs). However, the information regarding
      the causes or mechanism(s) responsible for Abeta accumulation in non-FADs is not
      as extensive and requires further elucidation. Simple sequence repeat (SSR)
      mediated molecular misreading has recently been implicated in Abeta accumulation,
      via neuronal expression of mutant forms of the Abeta precursor (APP+1) and
      ubiquitin-B (UBB+1) proteins. Also, additional studies have demonstrated that the
      enrichment or representation of SSRs correlates with the rate of such molecular
      misreading. Therefore, we have analyzed the representation of SSRs in the DNA
      sequences of selected AD genes (ADGs) and non-ADGs. SSRs of various motifs were
      found to be differentially enriched in both ADGs and non-ADGs. More importantly,
      all known AD-associated SSRs (ADSSRs) were found to be highly enriched in the APP
      and UBB genes. Since molecular misreading is believed to be a widespread
      phenomenon during aging, the high enrichment of ADSSRs in the APP and UBB genes
      suggests that older individuals may exhibit relatively high rates of neuronal
      expression of mutant APP+1 and UBB+1 peptides. This is consistent with the
      proposed involvement of these peptides in the pathogenesis of non-FADs.

PMID- 17531158
TI  - Down-regulation of ventricular nitric oxide generating system in chronic alcohol
      treated hypertensive rats.
AB  - Epidemiological studies show that low to moderate doses of alcohol consumption is
      beneficial to cardiac health. However, chronic high doses of alcohol ingestion
      cause cardiovascular complications including hypertension. The molecular and
      cellular mechanisms of chronic ethanol-induced increase in blood pressure (BP)
      are not completely understood. The purpose of this study was to investigate
      whether the increase in blood pressure following chronic ethanol exposure relates
      to cardiac endothelial nitric oxide levels and its generating system. Male Fisher
      rats were given 20% ethanol (4 g/kg, orally) through orogastric tube daily for 12
      weeks and controls received 5% sucrose through orogastric tube daily for 12
      weeks. The systolic, diastolic and mean BP was recorded through tail-cuff method.
      After 12 weeks, rats were sacrificed and heart dissected and left ventricle
      isolated and analyzed using enzyme linked immunosorbant assay (ELISA) and Western
      blotting. Results show that ethanol ingestion caused a significant increase in
      systolic, diastolic and mean BP (p<0.001) compared to control after 12 weeks. The
      levels of nitric oxide, its generating enzyme endothelial nitric oxide synthase
      (eNOS) protein expression and vascular endothelial growth factor (VEGF) gene
      (mRNA) and protein expressions were significantly down-regulated in the
      endothelium of left ventricles of ethanol-treated rats compared to controls. It
      is concluded that chronic ethanol ingestion causes an increase in blood pressure
      in rats via endothelial oxidative injury and the down-regulation of nitric oxide
      generating system in the left ventricles.

PMID- 17531159
TI  - Protein Kinase C- alpha/betaII, delta, and zeta/lambda involvement in ethanol
      induced MAPK expression in vascular smooth muscle cells.
AB  - Protein Kinase C (PKC) exists as one of twelve serine/threonine isoforms and has
      been found to mediate ethanol-induced activation of the Mitogen-Activated Protein
      Kinase (MAPK) pathway. The aim of this study was to determine the PKC isoform(s)
      that are mediators of ethanol-induced MAPK activity (ERK 1 and 2) and to verify
      the necessity of calcium in this activation process using cell culture in the
      presence and absence of ethanol, and other agents that modulate PKC expression.
      Western blotting analysis was used to assess the effect of ethanol on activating
      classical (alpha/ssII), novel (delta) and atypical (zeta/lambda) PKC isoforms in
      vascular smooth muscle cells (VSMCs). The results indicate that ethanol treated
      VSMCs express the classical PKC-alpha/ssII, novel PKC-delta, and atypical PKC
      zeta/lambda isoforms. The expression of PKC-alpha/ssII was inhibited within the
      first two min of stimulation, followed by activation with maximum expression at
      10 min. Similarly, PKC-delta and zeta expressions were suppressed during the
      first two min of ethanol stimulation with maximum increase in expressions at 10
      min. The PKC inhibitor GF109203X and the calcium chelating agent BAPTA, enhanced
      ethanol-induced PKC expression, whereas, diltiazem reduced expression of PKC by
      10% of control. On the other hand, BAPTA in the presence of GF10203X inhibited
      expression of ERK 1 & 2 downstream from the PKC pathway, whereas, BAPTA alone
      enhanced expression. These results demonstrate also that classical, novel, and
      atypical PKCs respond to ethanol during the initial phase of activation of ERK 1
      & 2.

PMID- 17531160
TI  - Heterogeneity of histamine H3 receptor genomic expression in the cerebral cortex
      of spontaneously hypertensive rat.
AB  - Specific binding of [3H]-N-alpha-methylhistamine to homogenates from cerebral
      cortex tissue was analyzed in aged Wistar Kyoto (WKY) and Spontaneously
      Hypertensive rats (SHR). Scatchard plot analysis of [3H]-N-alpha-methylhistamine
      binding of the H3 receptor in the cerebral cortex from aged (6, 9, 12, and 16
      week) SHR animals indicated that Bmax increased, respectively, 38.05 +/- 1.58,
      59.63 +/- 2.48, 79.17 +/- 5.02, and 84.41 +/- 3.72 fmol/mg of protein. Binding
      studies using tissue from WKY rats indicated that maximal binding (Bmax) of the
      ligand to the receptor was not significantly altered. The analyses also yielded
      Kd values of 5, 7.2, 6.3 and 3.8 nM in SHR tissue respectively. Primers based on
      the sequence of the third intracellular loop of the H3 receptor were amplified at
      35 cycles yielding several amplicons. These amplicons expressed sizes 875, 485,
      and 280 bp in 6 and 9 week cortical tissue from WKY animals where as in cortical
      tissue from 6 and 9 week SHR animals only two amplicons were expressed, 485 and
      280 bp, respectively. Differences in gene expression for 12 and 16 week WKY and
      SHR rats were also compared using identical primers. Five amplicons were
      expressed in cortical tissue from 12 and 16 week WKY rats with 1000, 900, 821,
      485, and 430 bp where as in 12 and 16 week SHR animals only one amplicon was
      expressed at 485 bp. The present results imply (1) that H3 receptor density in
      cortical tissue of SHR animals increases with age where as the number of the
      expressed amplicons of the detected H3 receptor decreases; and (2) even though a
      decrease in number of expressed amplicons of the H3 receptor were observed, an
      increase in expression of the larger amplicon (~500 bp) is evident.

PMID- 17531161
TI  - Induction of heme oxygenase-1 in renovascular hypertension is associated with
      inhibition of apoptosis.
AB  - The goal of this study was to characterize the impact of induction or inhibition
      of the heme-HO system on renal apoptosis in clipped and non-clipped kidneys from
      2K1C hypertensive rats. Male Sprague-Dawley rats had a 0.25 mm silver clip placed
      around the left renal artery. Four groups of rats were studied: sham operated
      animals, 2K1C control rats, 2K1C rats received weekly injections of CoPP (5
      mg/100 g body wt, administered subcutaneously), and 2K1C rats pretreated with
      SnMP (5 mg/ 100g body wt, administered intraperitoneally three times a week). The
      animals were sacrificed three weeks after surgery. We measured systolic blood
      pressure, plasma renin activity, non-clipped and clipped kidney HO-1 and HO-2
      protein expression, HO activity, heme content, nitrotyrosine levels, and
      activation of selected pro- and anti-apoptotic proteins. Systolic blood pressure
      and plasma renin activity were significantly higher in 2K1C rats compared to sham
      rats. Compared to kidneys from sham animals, clipped kidneys from 2K1C rats
      showed a significant increase in HO-1 expression with increases in HO activity
      (26%), heme content (47%) and nitrotyrosine levels (49%), accompanied by an
      increase in caspase-3 and caspase-9 activity. In contrast, non-clipped kidneys
      from 2K1C rats showed no differences in HO-1 expression, HO activity, heme
      content, nitrotyrosine levels and caspase activity compared to sham rats. In
      clipped kidneys from 2K1C rats, inhibition of HO activity by SnMP augmented
      caspase-3 and caspase-9 activity and decreased expression of the anti-apoptotic
      Bcl-2 protein, while induction of HO-1 with CoPP strongly inhibited the activity
      of both caspases and increased the induction of Bcl-2 and Bcl-xl proteins. These
      findings demonstrate that the clipped kidneys responded to decreased renal
      perfusion pressure and increased oxidative stress by activation of the heme-HO
      system, which exerts antiapoptotic action via mechanisms involving decreased
      caspase-3 and caspase-9 activity, and increased expression of antiapoptotic
      molecules.

PMID- 17531162
TI  - Cross-talking between calcium and histamine in the expression of MAPKs in
      hypertensive vascular smooth muscle cells.
AB  - Histamine (HA) is one of many neurotransmitters that have been implicated in
      cardiovascular functioning. Alterations in vascular smooth muscle due to the
      effects of histamine have been suggested. We investigated the modulatory effect
      of HA on mitogen activated protein kinase (MAPK) expression, specifically
      extracellular regulating kinase (ERK) 1 & 2 in vascular smooth muscle cells
      (VSMCs) from both spontaneously hypertensive (SHR) and control Wistar Kyoto (WKY)
      rats. Cross-talking between calcium (Ca2+) and HA during HA-induced modulatory
      effect on MAPK expression in SHR VSMCs was also investigated. A stimulatory
      increase in expression of ERK 1 & 2 was observed to be dose and time dependent
      with maximum expression occurring within 5 min in both SHR and WKY VSMCs. The
      stimulatory increase in expression is persistent for 60 min in SHR VSMCs,
      whereas, in WKY cells the stimulatory effect persists for only 20 min.
      Mepyramine, the H1 receptor antagonist, reduced the HA-induced increase in ERK 1
      & 2 significantly in SHR VSMCs. A reduction in the HA stimulated increase in ERK
      1 & 2 expression was observed at 20 min of exposing cells to diltiazem, the
      calcium channel blocker, whereas, the calcium chelator, BAPTA effect on ERK 1 & 2
      expression was observed within 5 min in SHR VSMCs. The data demonstrates that
      cross-talking occurs between HA stimulation and Ca2+ induction during HA-induced
      activation of ERK 1 & 2 in VSMCs of both cell types. Although both intracellular
      calcium ([Ca2+]i) and extracellular Ca2+ maybe involved in the activation of ERK
      1 & 2 by HA, the dependence on [Ca2+]i is more dramatic than the dependence on
      extracellular Ca2+ in hypertensive cells, which may contribute to the role of HA
      as a risk factor of hypertension in VSMCs of the aorta.

PMID- 17531163
TI  - Inclusion of high molecular weight dextran in calcium phosphate-mediated
      transfection significantly improves gene transfer efficiency.
AB  - Calcium phosphate-based mammalian cell transfection is a widely used gene
      transfer technology. To facilitate the efficiency of this gene transfer method,
      several polysaccharide compounds were tested and evaluated for their
      effectiveness in enhancing DNA transfection. Using a HIV-1-derived lentivirus
      vector plasmid as a gene transfer indicator, we demonstrated that the addition of
      high molecular weight dextran-500 at 0.6-1.2% in the 2x Hepes buffered saline
      (HBS) increased transfection efficiency by over 50% (as reflected by the number
      of GFP-positive cells) and increased the titer of resulting lentivirus vector
      particles even more (up to 4-fold). This enhancement of transfection efficiency
      was further increased when higher molecular weight dextran formulations were used
      in place of dextran-500, and also when dextran was used in combination with
      polybrene, another polycationic chemical compound. Examination of transfected
      cells showed that dextran had no apparent adverse effect on cell viability and
      growth. Our data represent the first report showing that dextran can be used to
      enhance calcium phosphate-mediated gene transfer; this may be useful in
      applications for the generation of high-titer virus vector stocks using transient
      transfection technology.

PMID- 17531164
TI  - Application of an ultraviolet (UV) spectroscopic method for measuring lipoprotein
      cholesterol in diabetic hypothyroid rats.
AB  - Methods for the isolation and quantitation of cholesterol involve time-consuming
      chromatographic procedures coupled with the development and measurement of color
      complexes. The intensity of most color complexes varies with time. This study was
      undertaken to develop a UV spectrophotometric method to measure cholesterol
      concentration in plasma lipoprotein fractions. The developed method compared
      favorably with other methods (chemical and enzymatic) and was then used to
      investigate the effects of diabetes and hypothyroidism on the lipoprotein
      cholesterol in rats. Lipoprotein fractions from fasted rats were obtained by
      gradient ultracentrifugation. Aliquots of the very low-density lipoprotein
      (VLDL), low-density lipoprotein (LDL) and high-density lipoprotein (HDL) layers
      were extracted into chloroform-methanol-water. Following hydrolysis of lipid
      extracts, the solvent was evaporated and the residue was dissolved in ethanol and
      read in the UV recording spectrophotometer. At 203 nm, a linear relationship
      between optical density and concentration of cholesterol was obtained. The
      results obtained with the new method were compared with those obtained using
      chemical and enzymatic methods and the statistical difference among the methods
      was insignificant (p>0.05). From the results of our comparative studies of the
      methods, it was concluded that the UV method is valid for measuring cholesterol
      in lipoprotein fractions. The method has the advantage being rapid,
      nondestructive and cost-effective.

PMID- 17531165
TI  - The characterization of the sol-gel encapsulated curcumin as a possible sensor
      for small biologically important molecules.
AB  - Curcumin, a known phytochemical antioxidant was found to be useful as a potential
      sensor for some small biologically important molecules. Hydrogen peroxide, the
      sodium salt of nitrite (NO2-), hydroxide (OH-), bromide (Br-) and iodide (I-)
      were observed to quench the fluorescence of sol-gel encapsulated curcumin, which
      emits radiation at 530 nm when excited at 420 nm. The observed bimolecular
      quenching constant which is related to the Stern-Volmer quenching constant, KSV,
      for the species studied in this work was determined by a modified Stern-Volmer
      relation for molecular surface accessibility, was observed to be specific for
      each of these anions and correlates quite well with their half-wave potentials,
      E1/2. The extent of permeability of these molecules through the pores of the sol
      gel matrix was determined and they, also, correlated with these molecules' charge
      densities and sizes. In all the species, the reaction was quite exergonic and the
      free energy change, DeltaGoET, obtained in each case, suggest an outer-sphere,
      long range electron transfer mechanism. These observations open up the possible
      use of curcumin as a sensor for probing and characterizing some relevant bio
      molecules in biological systems.

PMID- 17531166
TI  - Protective effect of an aqueous extract of Harpagophytum procumbens upon
      Escherichia coli strains submitted to the lethal action of stannous chloride.
AB  - Regardless of its lethal effects upon Escherichia coli (E. coli) cultures trough
      the production of free radicals (FR), stannous chloride (SnCl2) remains to be the
      most used reducing agent on the production of technetium-99m
      radiopharmaceuticals, to obtain images on nuclear medicine. Moreover, authors
      have reported that vegetal extracts are able to protect Escherichia coli cultures
      against the cytotoxicity of this agent. Harpagophytum procumbens, also known as
      Devil's Claw, is a plant used in folk medicine, as an analgesic and anti
      inflammatory in cases of joint and back pain, on the treatment of degenerative
      rheumatoid arthritis, osteoarthritis, kidney inflammation and heart diseases. The
      presence of this extract reduced the lesive effects of SnCl2 upon E. coli AB1157
      (proficient in DNA repair), BW9091 (deficient in the xthA gene) and BH110
      (deficient in the xthA, nfo and fpg genes) cultures, and the deficient strains
      (BW9091 e BH110) were more sensible to this SnCl2 action than the proficient one.
      The substances in the extract could be acting as: (i) chelator of the stannous
      ions, avoiding the generation of FR, (ii) FR scavenger, protecting the cells
      against the oxidation, and/or (iii) an oxidant compound acting upon the stannous
      ions, reducing the SnCl2 cytotoxicity.

PMID- 17531168
TI  - Secondary prevention: warfarin therapy in antiphospholipid syndrome.

PMID- 17531167
TI  - Macrovascular involvement in systemic sclerosis: comorbidity or accelerated
      atherosclerosis?

PMID- 17531169
TI  - Low molecular weight heparin to prevent antiphospholipid syndrome morbidity in
      pregnancy.

PMID- 17531170
TI  - High-intensity warfarin versus conventional antithrombotic therapy to prevent
      thrombosis in antiphospholipid syndrome.

PMID- 17531171
TI  - Mechanisms of aPL-mediated thrombosis: effects of aPL on endothelium and
      platelets.
AB  - Antiphospholipid antibodies (aPL) are associated with thrombosis and pregnancy
      loss in patients with systemic lupus erythematosus and antiphospholipid syndrome.
      Strong evidence demonstrates that aPL are pathogenic in vivo from studies that
      utilized animal models of thrombosis, endothelial cell activation, and pregnancy
      loss. However, the mechanisms by which aPL mediate disease are only partially
      understood, and our knowledge is limited by the polyspecificity of the
      antibodies, the multiple potential end-organ targets, and the variability of the
      clinical context in which the disease may present. This review discusses and
      summarizes the most current data available on molecular interactions and
      pathogenic mechanisms in antiphospholipid syndrome.

PMID- 17531172
TI  - Antiphospholipid antibody effects on monocytes.
AB  - Although the presence of autoantibodies is known to increase the risk of
      thrombosis in the antiphospholipid syndrome, the mechanism by which these
      antibodies exert their effects is poorly understood. Several studies suggest that
      autoantibody-mediated dysregulation of monocytes is one pathobiologic mechanism
      of this disease. Recent studies have focused on extra- and intracellular
      interactions involved in monocyte activation and expression of procoagulant
      activity. Agents specifically targeting monocyte activation and activity may
      provide a novel and efficacious approach that is safer than current
      antithrombotics.

PMID- 17531173
TI  - Role of complement in antiphospholipid antibody-mediated thrombosis.
AB  - The mechanisms by which an antibody that reacts with phospholipids (universal
      components of mammalian membranes) causes thrombosis are not immediately obvious.
      The development of an animal model of antiphospholipid antibody syndrome has
      moved the field forward in dissecting the pathogenesis of antiphospholipid
      antibody syndrome and has implicated the complement system in the mechanism of
      disease. Understanding complement's role in promoting thrombosis will be
      important in designing safer, more effective approaches to the treatment of
      patients with antiphospholipid antibodies, and may shed light on which patients
      are at greatest risk for thrombosis, perhaps permitting primary prophylaxis
      before irreversible tissue and organ damage occur.

PMID- 17531174
TI  - Antiphospholipid antibodies in response to infection.
AB  - An association between infections and antiphospholipid antibodies (aPL) has been
      reported in several epidemiologic and experimental studies. Infection-induced aPL
      have been traditionally regarded as transient and were generally not associated
      with clinical features of antiphospholipid syndrome. The distinction between
      autoimmune and postinfectious aPL on the basis of requirement of binding cofactor
      is not absolute, and in recent years, several reports demonstrated that some
      patients can produce pathogenic antibodies in response to infection. Infections
      most frequently associated with antiphospholipid syndrome include parvovirus B19,
      cytomegalovirus, varicella-zoster virus, HIV, streptococcal and staphylococcal
      infections, gram-negative bacteria, and Mycoplasma pneumoniae.

PMID- 17531175
TI  - Do antiphospholipid antibodies cause preeclampsia and HELLP syndrome?
AB  - Antiphospholipid syndrome (APS) is associated with adverse pregnancy outcomes
      including preeclampsia, recurrent early pregnancy loss, fetal death, and
      intrauterine growth restriction. Approximately one third of women with APS will
      develop preeclampsia during pregnancy. The association between antiphospholipid
      antibodies (aPL) in the absence of the clinical syndrome and preeclampsia is less
      clear, and a causal relationship has not yet been proven. Testing for aPL should
      be considered in women with early-onset (< 34 weeks) severe preeclampsia,
      eclampsia, or HELLP (hemolysis, elevated liver enzymes, and low platelets)
      syndrome, especially when additional clinical features of APS are present.
      Prospective testing for aPL in women at risk for preeclampsia is not recommended.
      Current evidence does not justify inclusion of preeclampsia as a major criterion
      for APS, but preeclampsia could reasonably be included as a secondary or minor
      criterion in diagnosis when a patient has other clinical features of APS.

PMID- 17531176
TI  - Last call for alcohol in gout?

PMID- 17531177
TI  - Genetic factors in the pathogenesis of CPPD crystal deposition disease.
AB  - Crystal deposition is a very complex process ruled by numerous factors. A small
      but important proportion of cases of chondrocalcinosis are monogenic, and many of
      the genes involved have been identified. These genetic findings strongly point to
      control of the level of extracellular inorganic pyrophosphate as the primary
      mechanism for their association with either calcium pyrophosphate dihydrate or
      hydroxyapatite deposition. However, effects on extracellular inorganic
      pyrophosphate levels do not explain the mechanism of association in all of these
      monogenic diseases. Further, there are likely to be several as yet unidentified
      genes that are important in this common condition. This review highlights what
      genetic studies have demonstrated about the processes involved in these diverse
      but related disorders.

PMID- 17531178
TI  - Tumoral calcinosis: new insights for the rheumatologist into a familial crystal
      deposition disease.
AB  - A growing body of evidence points to extraosseous calcification (calcification
      occurring in nonosseous tissues) as a major cause of morbidity and mortality in
      humans. The term familial tumoral calcinosis encompasses a number of rare
      recessive diseases, often associated with increased reabsorption of phosphate
      through the renal proximal tubule, which manifests with periarticular or acral
      calcium deposition. Recently, the molecular pathogenesis of this group of
      disorders has been elucidated, leading to the identification of several proteins
      playing pivotal roles in the regulation of extraosseous calcification. This
      report reviews these advances as well as the potential implications of these
      discoveries for the management of acquired conditions associated with abnormal
      calcification.

PMID- 17531179
TI  - Recent developments in crystal-induced inflammation pathogenesis and management.
AB  - Crystal-induced inflammation pathogenesis is undergoing a transition with respect
      to monosodium urate, calcium pyrophosphate dihydrate, and even basic calcium
      phosphate crystals. It is now recognized that innate immunity could be involved
      in the earlier pathogenic events and that the inflammasome, along with other
      signaling pathways, is activated and results in interleukin-1 processing and
      secretion, ultimately activating cells as a paracrine or autocrine cytokine.
      Management of acute and chronic monosodium urate crystal-induced inflammation,
      namely gout, has been critically reviewed by a dedicated European working group,
      and on the behalf of the European League against Rheumatism, 12 evidence-based
      recommendations have been reported. Calcium pyrophosphate dihydrate chronic
      inflammation could benefit from colchicine and from methotrexate as an anti
      inflammatory agent.

PMID- 17531180
TI  - Uric acid nephrolithiasis.
AB  - Uric acid nephrolithiasis is typically found in individuals with a low urine pH
      and a normal concentration of urinary uric acid. Patients with a history of gout
      are at greater risk of forming uric acid stones, as are patients with obesity,
      diabetes, or the complete metabolic syndrome. The unifying renal tubular
      abnormality of these disorders appears to be the excretion of abnormally acidic
      urine. This article focuses on the relationship of these disorders to the
      development of uric acid stones. The diagnosis of uric acid stones can be
      elusive, because pure uric acid stones are radiolucent on plain radiographs.
      Ultrasound, or preferably noncontrast helical CT scanning, is required for their
      detection. The treatment of uric acid stones should focus on alkalinization of
      the urine with citrate or bicarbonate salts. Additional interventions such as
      increase in fluid intake and decrease in animal protein ingestion are often
      beneficial. Patients with documented hyperuricemia often require specific therapy
      to lower serum uric acid concentration and subsequent excretion.

PMID- 17531181
TI  - Uricase and other novel agents for the management of patients with treatment
      failure gout.
AB  - Successful management of chronic gout depends on reducing body pools of urate.
      The benchmark of success is to maintain serum urate levels at less than 6 mg/dL
      using therapies such as probenecid or allopurinol. In a subset of patients with
      gout, these medications fail to achieve this benchmark, resulting in ongoing
      signs and symptoms characteristic of treatment-failure gout. Potential therapies
      now in clinical development show promise for treating this refractory patient
      population. In this article, we review the clinical characteristics associated
      with treatment-failure gout and discuss recent data from clinical trials of
      febuxostat and uricase.

PMID- 17531182
TI  - De-gassed water and surfactant-free emulsions: history, controversy, and possible
      applications.
AB  - Recent reports claiming stabilisation of surfactant-free oil-in-water emulsions
      (o/w SFEM's) have intrigued the colloid science community, and been reported in
      both the scientific literature and popular press. Key to the formation of SFEM's
      is a sequence of solidification by freeze quenching, degassing by action of
      vacuum, then thawing, known as freeze-pump-thaw (F-P-T). It is believed that the
      "emulsification" is caused by a reduction of hydrophobic interactions owing
      removal of dissolved gas after these F-P-T cycles. This review summarises
      literature on SFEM's, covering experiments, proposed mechanisms, and some
      potentially exciting applications.

PMID- 17531183
TI  - Decreasing photobleaching by silver island films: application to muscle.
AB  - Recently it has become possible to study interactions between proteins at the
      level of single molecules. This requires collecting data from an extremely small
      volume, small enough to contain one molecule-typically of the order of attoliters
      (10(-18) L). Collection of data from such a small volume with sufficiently high
      signal-to-noise ratio requires that the rate of photon detection per molecule be
      high. This calls for a large illuminating light flux, which in turn leads to
      rapid photobleaching of the fluorophores that are labeling the proteins. To
      decrease photobleaching, we measured fluorescence from a sample placed on
      coverslips coated with silver island films (SIF). SIF reduce photobleaching
      because they enhance fluorescence brightness and significantly decrease
      fluorescence lifetime. Increase in the brightness effectively decreases
      photobleaching because illumination can be attenuated to obtain the same
      fluorescence intensity. Decrease of lifetime decreases photobleaching because
      short lifetime minimizes the probability of oxygen attack while the fluorophore
      is in the excited state. The decrease of photobleaching was demonstrated in
      skeletal muscle. Myofibrils were labeled lightly with rhodamine-phalloidin,
      placed on coverslips coated with SIF, illuminated by total internal reflection,
      and observed through a confocal aperture. We show that SIF causes the intensity
      of phalloidin fluorescence to increase 4-5 fold and its fluorescence lifetime to
      decrease on average 23-fold. As a consequence, the rate of photobleaching of four
      or five molecules of actin of a myofibril on Olympus coverslips coated with SIF
      decreased at least 30-fold in comparison with photobleaching on an uncoated
      coverslip. Significant decrease of photobleaching makes the measurement of signal
      from a single cross-bridge of contracting muscle feasible.

PMID- 17531184
TI  - [Paradoxal growth hormone and cortisol response to hypoglycemia caused by
      endogenous hyperinsulinemia: a case report].
AB  - Growth hormone (GH) together with cortisol are two important counter-regulatory
      hormones maintaining normal glycemia. Hyperinsulinemic hypoglycemia is a disorder
      of this counter-regulation described in neonates. We report here a rare case of
      reversible dissociated hypopituitarism secondary to an insulinoma in a 38-year
      old man referred for investigation of hypoglycemic episodes. Hormonal
      investigations were in favour of dissociated anterior pituitary failure, with
      growth hormone and corticotroph deficiency. The hypothalamic-pituitary MRI was
      normal. The fasting test argued in favour of a hyperinsulinemic hypoglycemia. The
      abdominal scan and the endoscopic ultrasound showed a mass within the tail of the
      pancreas. Distal pancreatectomy was performed. Histology disclosed an insulinoma.
      On follow-up, no hypoglycemic episodes recurred and cortisol and GH response to
      induced hypoglycemia was normal. Our clinical case shows that hyperinsulinemia
      and hypoglycemia in patients with insulinoma can give rise to functional growth
      hormone and corticotrophin deficiency. The pathophysiological mechanism of this
      defective counter-regulation remains to be clarified; some studies suggest it
      could be related to hyperinsulinemia-induced decreased in CRF secretion and GHRH
      pulse.

PMID- 17531185
TI  - [Primary non-Hodgkin's lymphoma of the adrenals. A case report].
AB  - Bilateral primary non-Hodgkin's lymphoma (NHL) of the adrenals is uncommon. Less
      than 70 cases have been described in the literature. The symptoms of disease are
      variable and depend on the tumor size and the presence of adrenal insufficiency .
      We report a case of large diffuse B-cell adrenal lymphoma discovered in a 40-year
      old woman presenting bilateral lumbar pain. Hormonal exploration demonstrated
      adrenal insufficiency. Imaging explorations showed a large and bilateral adrenal
      mass. Percutaneous CT-guided biopsy of the adrenal and search for extension
      revealed primary bilateral adrenal lymphoma. After glucocorticoid substitution,
      treatment was based on a CHOP regimen chemotherapy; outcome was unfavourable
      after the second cure; the patient died from septic shock. The diagnosis of
      primary adrenal non-Hodgkin lymphoma should be investigated in patients with a
      rapidly growing bilateral adrenal mass associated with adrenal insufficiency.

PMID- 17531186
TI  - [Steroid responsive encephalopathy associated with auto-immune thyroiditis].
AB  - Since the first description of encephalopathy associated with Hashimoto's
      thyroiditis in 1966, more than 100 cases of this entity called Hashimoto's
      encephalopathy or SREAT [steroid-responsive encephalopathy associated with auto
      immune thyroiditis] have been reported. The two cases reported here illustrate
      different diagnostic criteria and offer the opportunity to discuss the many
      pathophysiological hypotheses based on particularly pertinent biological data,
      especially the activity of anti-TPO and anti-TG antibodies present in serum and
      cerebrospinal fluid and the recent discovery of anti-alpha-enolase antibody.
      Different treatment options are also discussed, in particular corticosteroid
      therapy.

PMID- 17531188
TI  - NOX in liver fibrosis.
AB  - NADPH oxidase is a multi-protein complex producing reactive oxygen species (ROS)
      both in phagocytic cells, being essential in host defense, and in non-phagocytic
      cells, regulating intracellular signalling. In the liver, NADPH oxidase plays a
      central role in fibrogenesis. A functionally active form of the NADPH oxidase is
      expressed not only in Kupffer cells (phagocytic cell type) but also in hepatic
      stellate cells (HSCs) (non-phagocytic cell type), suggesting a role of the non
      phagocytic NADPH oxidase in HSC activation. Consistent with this concept,
      profibrogenic agonists such as Angiotensin II (Ang II) and platelet derived
      growth factor (PDGF), or apoptotic bodies exert their activity through NADPH
      oxidase-activation in HSCs. Both pharmacological inhibition with DPI and genetic
      studies using p47(phox) knockout mice provided evidence for a central role of
      NADPH oxidase in the regulation of HSC-activity and liver fibrosis. In addition
      to the p47(phox) component, only Rac1 has been identified as a functional active
      component of the NADPH oxidase complex in HSCs.

PMID- 17531189
TI  - Trafficking of the copper-ATPases, ATP7A and ATP7B: role in copper homeostasis.
AB  - Copper is essential for human health and copper imbalance is a key factor in the
      aetiology and pathology of several neurodegenerative diseases. The copper
      transporting P-type ATPases, ATP7A and ATP7B are key molecules required for the
      regulation and maintenance of mammalian copper homeostasis. Their absence or
      malfunction leads to the genetically inherited disorders, Menkes and Wilson
      diseases, respectively. These proteins have a dual role in cells, namely to
      provide copper to essential cuproenzymes and to mediate the excretion of excess
      intracellular copper. A unique feature of ATP7A and ATP7B that is integral to
      these functions is their ability to sense and respond to intracellular copper
      levels, the latter manifested through their copper-regulated trafficking from the
      transGolgi network to the appropriate cellular membrane domain (basolateral or
      apical, respectively) to eliminate excess copper from the cell. Research over the
      last decade has yielded significant insight into the enzymatic properties and
      cell biology of the copper-ATPases. With recent advances in elucidating their
      localization and trafficking in human and animal tissues in response to
      physiological stimuli, we are progressing rapidly towards an integrated
      understanding of their physiological significance at the level of the whole
      animal. This knowledge in turn is helping to clarify the biochemical and cellular
      basis not only for the phenotypes conferred by individual Menkes and Wilson
      disease patient mutations, but also for the clinical variability of phenotypes
      associated with each of these diseases. Importantly, this information is also
      providing a rational basis for the applicability and appropriateness of certain
      diagnostic markers and therapeutic regimes. This overview will provide an update
      on the current state of our understanding of the localization and trafficking
      properties of the copper-ATPases in cells and tissues, the molecular signals and
      posttranslational interactions that govern their trafficking activities, and the
      cellular basis for the clinical phenotypes associated with disease-causing
      mutations.

PMID- 17531190
TI  - Papillomavirus binding factor (PBF)-mediated inhibition of cell growth is
      regulated by 14-3-3beta.
AB  - The cellular factor, papillomavirus (PV)-binding factor (PBF)/Huntington's
      disease binding protein 2 (HDBP2), was identified by its ability to bind
      regulatory sequences of certain papillomavirus types as well as the Huntington's
      disease gene. PBF is thought to be a novel nuclear-shuttling transcription factor
      with unknown function. To further characterize PBF, we identified 14-3-3beta as
      an interaction partner. We demonstrated that PBF binds to 14-3-3beta using two
      motifs. Akt-kinase and an unidentified kinase that are activated by the PI3K
      signaling pathway were able to phosphorylate these motifs, allowing PBF to
      associate with 14-3-3beta. This interaction may contribute to the control of the
      subcellular localization of PBF, which migrated into the nucleus in the absence
      of growth factors. Over-expression of PBF resulted in the inhibition of cell
      growth, which was enhanced using a 14-3-3 binding-deficient PBF mutant. Thus, our
      experiments characterized PBF as a new cellular factor mediating the effects of
      PI3K/Akt signaling and 14-3-3 on cell growth.

PMID- 17531191
TI  - Development of a specific inhibitor for the placental protease, cathepsin P.
AB  - Gene duplications in rodents have given rise to a family of proteases that are
      expressed exclusively in placenta. To define the biological role of these enzymes
      specific inhibitors are needed to differentiate their activities from other more
      ubiquitously expressed proteases, such as cathepsins B and L. Libraries of
      peptidyl inhibitors based upon a 4-cyclohexanone pharmacophore were screened for
      inhibition of cathepsins P, L, and B. The tightest binding dipeptidyl inhibitor
      for cathepsin P contained Tyr in P(2) and Trp in P(2)('), consistent with the
      specificity of this enzyme for hydrophobic amino acids at these sites in
      synthetic substrates. An inhibitor containing Trp in both P(2) and P(2)(')
      provided better discrimination between cathepsin P and cathepsins B and L.
      Extension of the inhibitors to include P(3), and P(3)(') amino acids identified
      an inhibitor with Trp in P(2), P(2)('), and P(3), and Phe in P(3)(') that bound
      to cathepsin P with a K(i) of 32 nM. This specificity for inhibitors with
      hydrophobic aromatic amino acids in these four positions is unique among the
      lysosomal cysteine proteases. This inhibitor bound to cathepsin P an order of
      magnitude tighter than to mouse and human cathepsin L and two orders of magnitude
      tighter than to human cathepsin B. Cbz-Trp-Trp-4-cyclohexanone-Trp-Phe-OMe can
      discriminate cathepsin P from cathepsins B and L and consequently can be used to
      specifically inhibit and identify cathepsin P in cellular systems.

PMID- 17531192
TI  - Child maltreatment, non-suicidal self-injury, and the mediating role of self
      criticism.
AB  - We examined the relation between child maltreatment and non-suicidal self-injury
      (NSSI). Participants were 86 adolescents who completed measures of child
      maltreatment, self-criticism, perceived criticism, depression, and NSSI. Analyses
      revealed significant, small-to-medium associations between specific forms of
      child maltreatment (physical neglect, emotional abuse, and sexual abuse) and the
      presence of a recent history of NSSI. Emotional and sexual abuse had the
      strongest relations with NSSI, and the data supported a theoretical model in
      which self-criticism mediates the relation between emotional abuse and engagement
      in NSSI. Specificity for the mediating role of self-criticism was demonstrated by
      ruling out alternative mediation models. Taken together, these results indicate
      that several different forms of childhood maltreatment are associated with NSSI
      and illuminate one mechanism through which maltreatment may be associated with
      NSSI. Future research is needed to test the temporal relation between
      maltreatment and NSSI and should aim to identify additional pathways to
      engagement in NSSI.

PMID- 17531193
TI  - Psychological trauma and PTSD symptoms as predictors of substance dependence
      treatment outcomes.
AB  - Psychological trauma and post-traumatic stress disorder (PTSD) may complicate and
      reduce the effectiveness of treatment for substance use disorders (SUDs). This
      study assessed trauma history and symptoms of simple and complex PTSD at baseline
      in a randomized trial of contingency management (CM) compared to standard
      treatment (ST) with 142 cocaine- or heroin-dependent outpatients. History of
      exposure to each of eight types of psychological trauma was unrelated to
      treatment outcome, except for witnessed assaults and emotional abuse. Complex
      PTSD symptoms were inversely associated with short-term treatment outcomes, and
      PTSD symptoms were positively related to long-term outcome, independent of the
      effects of demographics, psychological distress, baseline substance use status,
      and treatment modality. Complex PTSD symptoms warrant further study as a
      potential negative prognostic factor in SUD interventions.

PMID- 17531194
TI  - Roles of oxidative stress and Akt signaling in doxorubicin cardiotoxicity.
AB  - Cardiotoxicity is a treatment-limiting side effect of the anticancer drug
      doxorubicin (DOX). We have now investigated the roles of oxidative stress and
      signaling by the protein kinase Akt in DOX-induced cardiotoxicity as well as the
      effects on such toxicity both of fenofibrate, an agonist of peroxisome
      proliferator-activated receptor-alpha, and of polyethylene glycol-conjugated
      superoxide dismutase (PEG-SOD), an antioxidant. Mice injected intraperitoneally
      with DOX were treated for 4 days with fenofibrate or PEG-SOD. Fenofibrate and PEG
      SOD each prevented the induction of cardiac dysfunction by DOX. Both drugs also
      inhibited the activation of the transcription factor NF-kappaB and increase in
      lipid peroxidation in the left ventricle induced by DOX, whereas only PEG-SOD
      inhibited the DOX-induced activation of Akt and Akt-regulated gene expression.
      These results suggest that fenofibrate and PEG-SOD prevented cardiac dysfunction
      induced by DOX through normalization of oxidative stress and redox-regulated NF
      kappaB signaling.

PMID- 17531195
TI  - Hepatocytes maintain their function on basement membrane formed by epithelial
      cells.
AB  - To establish liver tissue engineering, the effective substratum for hepatocytes
      culture should be developed. Up to now, it is believed that Matrigel, which
      contains several basement membrane proteins produced by sarcoma cells, is the
      most effective substratum. Matrigel does not contain extracellular matrix
      molecules derived from epithelial cells although the space of Disse contains the
      molecules such as laminin-511/521 (laminin-10/11). Therefore, the basement
      membrane formed by epithelial cells can be more effective substratum than
      Matrigel. In this study, we evaluated hepatocytes behavior on basement membrane
      (rBM) formed by alveolar epithelial cells. The viability of hepatocytes on rBM is
      higher than that of Matrigel within 5 days. Also, the expression of Cyp1a2
      induced by beta-naphthoflavone can be observed in hepatocytes on rBM but not in
      Matrigel. These results indicate that rBM is a more effective substratum for
      hepatocyte culture than Matrigel.

PMID- 17531196
TI  - Development and characterization of a recombinant cDNA-based hepatitis C virus
      system.
AB  - Invention of subgenomic HCV replicon a few years ago and recent success of in
      vitro production of infectious HCV have improved our knowledge of the HCV life
      cycle, replication, pathogenesis, and screening of anti-HCV therapeutics.
      However, the highly genotype-dependent nature of the in vitro HCV production
      system has limited its potential for HCV research. In this study, we constructed
      a recombinant DNA-based HCV system that contained EF-1alpha promoter-driven HCV
      genotype 1b with HCV E1/E2 deleted and replaced by GFP. We co-transfected this
      recombinant cDNA with HCV E1/E2 or VSV-G expression plasmid into 293T cells, and
      we showed HCV protein expression and processing and demonstrated production of
      HCV-like particles in culture supernatant of co-transfected cells. These results
      support potential use of this system for studies on expression and processing of
      the HCV polyprotein and assembly and release of HCV-like particles.

PMID- 17531197
TI  - Basic fibroblast growth factor promotes bone marrow stromal cell transplantation
      mediated neural regeneration in traumatic brain injury.
AB  - The current study was designed to evaluate the effects of basic fibroblast growth
      factor (bFGF) on human BMSC (hBMSC) transplantation-mediated neural regeneration
      in traumatic brain injury (TBI). Fibrin gel was used as a delivery vehicle to
      release bFGF locally in the TBI sites in a controlled manner. To test this
      hypothesis, hBMSCs suspended in fibrin gel containing bFGF were transplanted to
      rat TBI sites. Transplantation of hBMSCs suspended in fibrin gel without bFGF
      served as a control. hBMSC transplantation and bFGF treatment showed enhanced
      neural tissue regeneration than that of the control. The infarction volume and
      apoptotic activity of the transplanted hBMSCs were significantly decreased, and
      functional outcomes were significantly improved in the hBMSC transplantation and
      bFGF treatment group than in the control group. This study demonstrates that bFGF
      significantly enhances histological and functional recovery when used in hBMSC
      transplantation therapy in TBI.

PMID- 17531198
TI  - Cloning, expression, and functional characterization of zebrafish Mist1.
AB  - The basic helix-loop-helix (bHLH) protein Mist1 is an important exocrine pancreas
      transcriptional factor expressed in the acinar cells of mammals. In the present
      study, we cloned the homologous Mist1 cDNA encoding a predicted protein of 184
      amino acids in zebrafish. The typical bHLH domain of zebrafish Mist1 shares high
      identity with that of its orthologs in mouse, rat, and human. Expression analysis
      revealed that Mist1 maternal transcripts are distinct in the very beginning of
      embryogenesis and that endogenous Mist1 is chronologically expressed in polster,
      hatching gland, hindbrain and appears exclusively in the pancreas from 72 hpf
      onward. Knockdown of Mist1 conditionally causes mild morphological defects in
      embryos. In MO-treated embryos, midbrain-hindbrain boundary is missing and
      exocrine pancreas is significantly reduced and disorganized. These results
      suggest that Mist1 functions in an evolutionary conserved way as a key
      transcriptional regulator specific for exocrine pancreas development in
      zebrafish.

PMID- 17531199
TI  - CaIPF7817 is involved in the regulation of redox homeostasis in Candida albicans.
AB  - CaIPF7817, a functionally unknown gene in Candida albicans, was suggested to be
      involved in the redox system previously, but its exact role is unknown. In this
      study, ipf7817 null mutant was generated with the URA-blaster method. After the
      deletion of CaIPF7817, intracellular levels of reactive oxygen species were
      significantly increased; mitochondrial membrane potential, a direct indicator of
      mitochondrial function, was elevated; some important redox-related genes,
      including GLR1, SOD2, and TRR1, were up-regulated; and the GSH/GSSG ratio was
      raised. These changes indicated that CaIPF7817 played important roles in the
      regulation of redox homeostasis in C. albicans.

PMID- 17531200
TI  - A new calcineurin inhibition domain in Cabin1.
AB  - Calcineurin (CN), a calcium-activated phosphatase, plays a critical role in
      various biological processes including T cell activation. Cabin1, a calcineurin
      binding protein 1, has been shown to bind directly to CN using its C-terminal
      region and inhibit CN activity. However, no increase in CN activity has been
      found in Cabin1DeltaC T cells, which produce a truncated Cabin1 lacking the C
      terminal CN binding region. Here, we report that Cabin1 has additional CN binding
      domain in its 701-900 amino acid residues. Cabin1 (701-900) blocked both CN
      mediated dephosphorylation and nuclear import of NFAT and thus inhibited IL-2
      production in response to PMA/ionomycin stimulation. This fact may explain why
      Cabin1DeltaC mice previously showed no significant defect in CN-mediated
      signaling pathway.

PMID- 17531201
TI  - Anti-angiogenic peptides identified in thrombospondin type I domains.
AB  - Thrombospondin 1, the prototypical protein of the thrombospondin protein family,
      is a potent endogenous inhibitor of angiogenesis. Although the effects of the
      thrombospondin 1 on neovascularization have been well studied, little is known
      about the anti-angiogenic potency of other proteins or peptide fragments derived
      from the proteins in this family. Here we identify a set of 18 novel, anti
      angiogenic 17- to 20-amino acid peptides that are derived from proteins
      containing type I thrombospondin motifs. We have named these peptides
      adamtsostatin-4, adamtsostatin-16, adamtsostatin-18, cartilostatin-1,
      cartilostatin-2, fibulostatin-6.2, fibulostatin-6.3, papilostatin-1, papilostatin
      2, properdistatin, scospondistatin, semastatin-5A.1, semastatin-5A.2, semastatin
      5B, thrombostatin containing-1, thrombostatin contaning-3, thrombostatin
      contaning-6, and wispostatin-1 to reflect their origin. We further demonstrate
      that these peptides inhibit the proliferation and migration of human umbilical
      vein endothelial cells in vitro. The anti-proliferative and anti-migratory
      properties of the identified peptides may be important in maintaining angiogenic
      homeostasis in vivo and make these peptides suitable candidates for use as anti
      angiogenic pharmaceutical agents in numerous therapeutic applications.

PMID- 17531202
TI  - Hydrogen sulphide regulates intracellular pH in vascular smooth muscle cells.
AB  - We investigated the role of hydrogen sulphide (H(2)S) in intracellular pH (pH(i))
      regulation in vascular smooth muscle cells and its contribution on vasodilation.
      NaHS, a H(2)S donor, decreased pH(i) in a concentration-dependent manner ranging
      from 10 microM to 1mM. Neither inhibition of the Na(+)/H(+) exchanger with 5-(N
      ethyl-N-isopropyl) amiloride, (EIPA, 10 microM), nor plasmalemmal Ca(2+)-ATPase
      with CdCl(2) (20nM) alters the effect of NaHS on pH(i). Blockade of the Cl(
      )/HCO3- exchanger with 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS)
      significantly attenuated the pH(i) lowering effect of NaHS. Moreover, NaHS
      significantly increased the activity of Cl(-)/HCO3- exchanger when measured with
      NH(4)Cl prepulse method. DIDS attenuated the vasorelaxation induced by NaHS
      whereas EIPA and CdCl(2) did not cause any change. In conclusion, H(2)S induced
      intracellular acidification via activation of Cl(-)/HCO3- exchanger, which is, at
      least partially, responsible for H(2)S-mediated vasorelaxation.

PMID- 17531203
TI  - Amiodarone inhibits tocopherol-mediated human lipoprotein peroxidation.
AB  - It is unknown whether lipoprotein tocopherol-mediated peroxidation (TMP) is
      influenced by peculiar drug physicochemical properties such as hydrophobicity.
      Thus, we studied the effect of the extremely hydrophobic agent amiodarone on
      human non-HDL TMP. The drug, albeit devoid of specific radical-scavenging
      effects, inhibited TMP at therapeutic concentrations and with an efficiency
      similar to that of the physiological co-antioxidant ascorbic acid, showing indeed
      an IC(50) of 5microM. A comparable efficiency was observed with human LDL, and
      with a pure LDL-VLDL mixture. TMP was also inhibited by other hydrophobic
      cationic amphiphiles without radical-scavenging activity, namely
      desethylamiodarone, chlorpromazine, clomipramine, promethazine, promazine,
      verapamil, bromhexine, propranolol, mepivacaine, metoprolol, tramadol and
      ranitidine, whose anti-TMP potency was far lower than that of amiodarone and
      related to drug hydrophobicity degree. Further, TMP was strongly inhibited by
      butylhydroxytoluene, a lipophilic radical scavenger. Hydrophobic acidic
      (diclofenac, indomethacin, ibuprofen and ketoprofen) or neutral (n-hexane,
      anthracene, o-xylene and toluene) compounds could not instead inhibit TMP,
      indicating a stringent requirement for drug basicity in the pharmacological
      inhibition of TMP. Amiodarone effectiveness was lowered by lipoprotein alpha
      tocopherol enrichment, suggesting some drug-alpha-tocopherol interaction and less
      lipid pharmacological protection at higher alpha-tocopheroxyl radical generation.
      Drug anti-TMP activity may so be related to electrostatic and hydrophobic
      interactions with lipoprotein alpha-tocopherol and lipid moiety, resulting in
      decreased radical phase transfer and lipid propensity to undergo radical-driven
      peroxidation. In conclusions, primarily drug basicity and then hydrophobicity are
      solely relevant to TMP inhibition. Amiodarone, at therapeutic concentrations, has
      anti-TMP properties, which could occur in the clinical setting.

PMID- 17531204
TI  - Comments on Fearful and sexual pictures not consciously seen modulate the startle
      reflex in human beings.

PMID- 17531205
TI  - Regarding "The Munich vulnerability study on affective disorders: premorbid
      polysomnographic profile of affected high-risk probands".

PMID- 17531206
TI  - Abnormal magnocellular pathway visual processing in infants at risk for autism.
AB  - BACKGROUND: A wealth of data has documented impairments in face processing in
      individuals with autism spectrum disorders (ASD). Recently, the suggestion has
      been made that these impairments may arise from abnormal development of a
      subcortical system involved in face processing that originates in the
      magnocellular pathway of the primate visual system. METHODS: To test this
      developmental hypothesis, we obtained visual perceptual data from 6-month-old
      infants who were at risk for ASD because they had an older sibling diagnosed with
      the disorder ("high-risk infants"). To measure sensitivity of the magnocellular
      (M) pathway and, for comparison, of the parvocellular (P) visual pathway, we
      employed visual stimuli designed to selectively stimulate the two. Sensitivity
      data from high-risk infants (n = 13) were compared with data from matched control
      infants (i.e., "low-risk" infants with no family history of ASD, n = 26).
      RESULTS: On the P pathway stimulus, high-risk infants exhibited sensitivities
      that were identical to those of control infants. By contrast, on the M pathway
      stimulus, high-risk infants exhibited sensitivities nearly twofold greater than
      those of control infants. CONCLUSIONS: Given that ASD and its symptoms are known
      to run in families, these preliminary results suggest that ASD may be associated
      with abnormal M pathway function early in infancy, which may aid in early
      diagnosis of the disorder.

PMID- 17531207
TI  - Altered dimerization of metabotropic glutamate receptor 3 in schizophrenia.
AB  - BACKGROUND: Metabotropic glutamate receptors (mGlus) may be involved in the
      pathophysiology of schizophrenia. Group II mGlus (mGlu2 and mGlu3) have attracted
      considerable interest since the development of potent specific agonists that
      exhibit atypical antipsychotic-like activity and reports of a genetic association
      between the mGlu3 gene and schizophrenia. METHODS: In this postmortem study,
      mGlu3 protein levels in Brodmann area 10 of prefrontal cortex from schizophrenic
      (n = 20) and control (n = 35) subjects were analyzed by western immunoblotting
      using a novel specific mGlu3 antibody and an antibody for the vesicular glutamate
      transporter 1 (VGluT1). RESULTS: We report a significant decrease in the
      dimeric/oligomeric forms of mGlu3 in schizophrenic patients compared with control
      subjects, whereas total mGlu3 and VGluT1 levels were not altered significantly.
      CONCLUSIONS: This is the first experimental evidence that mGlu3 receptor levels
      are altered in schizophrenia and supports the hypothesis that neurotransmission
      involving this particular excitatory amino acid receptor is impaired in
      schizophrenia.

PMID- 17531208
TI  - Inactivation of the 5-HT(7) receptor partially blocks phencyclidine-induced
      disruption of prepulse inhibition.
AB  - BACKGROUND: Studies have implicated the serotonin (5-HT)(7) receptor in
      physiological and pathophysiological phenomena, including thermoregulation,
      central control of micturition and locomotion, regulation of circadian rhythm,
      sleep, and depression. Further, several antidepressant and antipsychotic drugs
      have high affinity for the 5-HT(7) receptor. METHODS: We examined the role of 5
      HT(7) receptors in a rodent analogue of sensorimotor gating deficits in
      schizophrenia: phencyclidine (PCP)-induced disruption of prepulse inhibition
      (PPI) of acoustic startle. We used mice lacking the 5-HT(7) receptor due to a
      targeted inactivation of this receptor gene and the selective 5-HT(7) receptor
      antagonist SB-269970. RESULTS: SB-269970 did not affect either baseline PPI or
      PCP-disrupted PPI. There was no difference between 5-HT(7)(+/+) and 5-HT(7)(-/-)
      mice in startle reactivity or PPI regardless of prepulse intensity (74-82 dB),
      interstimulus interval (25-500 msec), or pulse intensity (90-120 dB).
      Nevertheless, disruption of PPI produced by PCP (10 mg/kg) in wild-type mice was
      reduced in 5-HT(7)(-/-) mice, although it was not affected by the 5-HT(7)
      antagonist SB-269970. By contrast, the PPI-disruptive effects of apomorphine (5
      mg/kg) and amphetamine (7.5 mg/kg) were comparable in both genotypes.
      CONCLUSIONS: The results indicate a partial role for the 5-HT(7) receptor in the
      glutamatergic PPI model of sensorimotor gating deficits in schizophrenia that is
      sensitive to atypical antipsychotics and no involvement of this receptor in the
      dopaminergic PPI model that is sensitive to typical antipsychotics. Thus, the 5
      HT(7)(-/-) mice may provide a useful tool to study the role of 5-HT(7) receptor
      in the action of atypical antipsychotic drugs and schizophrenia.

PMID- 17531209
TI  - TNFalpha siRNA reduces brain TNF and EEG delta wave activity in rats.
AB  - Tumor necrosis factor alpha (TNFalpha) is a pleiotropic cytokine with several CNS
      physiological and pathophysiological actions including sleep, memory, thermal and
      appetite regulation. Short interfering RNAs (siRNA) targeting TNFalpha were
      incubated with cortical cell cultures and microinjected into the primary
      somatosensory cortex (SSctx) of rats. The TNFalpha siRNA treatment specifically
      reduced TNFalpha mRNA by 45% in vitro without affecting interleukin-6 or gluR1-4
      mRNA levels. In vivo the TNFalpha siRNAalpha reduced TNFalpha mRNA, interleukin-6
      mRNA and gluR1 mRNA levels compared to treatment with a scrambled control siRNA.
      After in vivo microinjection, the density of TNFalpha-immunoreactive cells in
      layer V of the SSctx was also reduced. Electroencephalogram (EEG) delta wave
      power was decreased on days 2 and 3 on the side of the brain that received the
      TNFalpha siRNA microinjection relative to the side receiving the control siRNA.
      These findings support the hypothesis that TNFalpha siRNA attenuates TNFalpha
      mRNA and TNFalpha protein in the rat cortex and that those reductions reduce
      cortical EEG delta power. Results also are consistent with the notion that
      TNFalpha is involved in CNS physiology including sleep regulation.

PMID- 17531210
TI  - S100 proteins: a missing piece in the puzzle of heart failure?

PMID- 17531211
TI  - FcgammaRIIa mediates C-reactive protein-induced inflammatory responses of human
      vascular smooth muscle cells by activating NADPH oxidase 4.
AB  - OBJECTIVES: We investigated the mechanism by which C-reactive protein (CRP)
      affects pro-inflammatory activities of vascular smooth muscle cells (VSMCs).
      METHODS AND RESULTS: RT-PCR, flow cytometry, and immunoblotting assays
      consistently showed the expression of FcgammaRIIa by cultured VSMCs isolated from
      human coronary arteries. Immunofluorescence staining of human coronary artery
      plaque showed the co-localization of FcgammaRIIa with alpha-actin(+) VSMCs in
      atheromatous regions. Confocal microscopic image analysis of H(2)DCFDA-labeled
      cells showed that CRP induced intracellular reactive oxygen species (ROS)
      generation by FcgammaRIIa(+) HEK293T cells. Moreover, CRP time- and dose
      dependently generated ROS in VSMCs through FcgammaRIIa activation. VSMCs mainly
      express NADPH oxidase 4 isoform (Nox4), the suppression of which using a specific
      siRNA completely abolished CRP-induced ROS generation by VSMCs. The
      downregulation of p22(phox), a component of the active Nox4 complex, by
      transfecting with specific decoy oligomers and functional blocking of FcgammaRIIa
      not only inhibited the CRP-induced ROS generation but also reduced the degree of
      AP-1 and NF-kappaB activation, the production of MCP-1, IL-6, and ET-1, and the
      apoptotic changes of VSMCs in response to CRP. CONCLUSIONS: CRP-induced ROS
      generation by VSMCs, which requires functional activation of FcgammaRIIa and
      NADPH oxidase 4, orchestrates pro-inflammatory activities of VSMCs and may
      eventually promote atherogenesis and plaque rupture.

PMID- 17531212
TI  - Understanding the cardiac role of K2P channels: a new TASK for
      electrophysiologists.

PMID- 17531213
TI  - The Amsterdam years.

PMID- 17531214
TI  - Regulation of endothelial barrier function during flow-induced conversion to an
      arterial phenotype.
AB  - OBJECTIVE: Flow-induced conversion of endothelial cells into an elongated
      arterial phenotype requires a coordinated regulation of cell junctions. Here we
      investigated the effect of acute and chronic flow on junction regulation. METHODS
      AND RESULTS: Using an extended experimental setup that allows analyses of
      endothelial barrier function under flow conditions, we found a flow-induced
      upregulation of the transendothelial electrical resistance within minutes. This
      was accompanied by an increase in actin filaments along the junctions and
      vascular endothelial (VE)-cadherin clustering, which was identified at nanoscale
      resolution by stimulated emission depletion microscopy. In addition, a transient
      tyrosine phosphorylation of VE-cadherin and catenins occurred within minutes
      following the onset of flow. VE-cadherin and actin distribution were maintained
      under chronic flow over 24 h and associated with the upregulation of VE-cadherin
      and alpha-catenin expression, thus compensating for the cell elongation-mediated
      increase in cell border length. Importantly, all observed effects were rac1
      dependent as verified by the inhibitory effect of dominant negative N17rac1.
      CONCLUSION: These results show that flow-induced conversion of endothelial cells
      into an arterial phenotype occurs while intercellular junctions remain intact.
      The data place rac1 in a central multimodal regulatory position that might be
      important in the development of vascular diseases, such as arteriosclerosis.

PMID- 17531215
TI  - Mechanism of U wave and polymorphic ventricular tachycardia in a canine tissue
      model of Andersen-Tawil syndrome.
AB  - OBJECTIVE: Andersen-Tawil syndrome (ATS) is a channelopathy affecting inward
      rectifier potassium I(K1) with QT prolongation, large U waves, and frequent
      ventricular tachycardia (VT). Although ATS is clinically defined and genetically
      identified, its electrophysiological mechanism is still unclear, and thus, was
      the subject of the current study. METHODS AND RESULTS: We replicated the major
      electrophysiological features of ATS with cesium chloride (CsCl, at I(K1)
      blockade concentration of 5-10 mmol/l) in 23 isolated canine left ventricular
      tissues perfused arterially with Tyrode's solution having normal or low potassium
      concentrations, [K(+)](o). We mapped action potentials (APs) on the cut-exposed
      transmural surface of the wedges in control, after CsCl, and CsCl with 0.15
      mumol/l isoproterenol (CsCl+ISP). CsCl delayed late phase 3 repolarization and
      prolonged the duration of the AP, more so during low [K(+)](o) perfusion. Rapid
      pacing induced delayed afterdepolarizations (DADs) in all low [K(+)](o) and in
      71% of normal [K(+)](o) preparations after CsCl treatment. Addition of ISP
      induced DADs in all preparations. DADs originated in mid-to-endocardium, and
      initiated VT after CsCl+ISP. Migration of DAD-VT foci resulted in multifocal VT.
      Alternating DADs at 2 foci resulted in bidirectional VT. There were more foci and
      longer durations of VT at low [K(+)](o) than at normal [K(+)](o). Delayed late
      phase 3 repolarization of APs and DADs generated U waves. Verapamil abolished all
      DADs and VT. CONCLUSIONS: CsCl blockade of I(K1) produced a ventricular wedge
      model of ATS. Suppressing I(K1) generated U waves by delaying late repolarization
      of APs and creating DADs, and promoted polymorphic VT by triggering DADs at
      multiple shifting sites.

PMID- 17531216
TI  - Pleural fluid neopterin levels in tuberculous pleurisy.
AB  - OBJECTIVES: Neopterin is produced by stimulated macrophages under the influence
      of gamma interferon of lymphocyte origin. It is regarded as a biochemical marker
      of cell-mediated immune response. This study was designed to assess the
      diagnostic value of pleural fluid neopterin levels in tuberculous pleurisy in
      comparison with adenosine deaminase activity. DESIGN AND METHODS: Pleural fluid
      adenosine deaminase (ADA) activity and neopterin levels were measured in 16
      patients with tuberculous pleurisy (TP) and 19 patients with malignant pleurisy
      (MP). ADA activity was determined by a colorimetric method, whereas neopterin
      levels were determined by a reversed-phase liquid chromatography technique. All
      values were given as median (min-max). RESULTS: The mean age was 45.43+/-20.39
      years in the TP group and 60.42+/-11.02 years in the MP group (p=0.026). The
      median pleural fluid ADA activity was 51.75 U/L (3.50-62.40 U/L) in the TP group
      and was 2.30 U/L (1-8.20 U/L) in the MP group. The difference was statistically
      significant (p<0.001). The median pleural fluid neopterin levels were 13.15
      nmol/L (1.86-59.50 nmol/L) and 2.44 nmol/L (0.92-27.60 nmol/L) in the TP group
      and the MP group, respectively (p=0.021). In order to evaluate the diagnostic
      value of pleural fluid neopterin concentrations, receiver-operating
      characteristic curve analysis was performed. CONCLUSION: Pleural fluid neopterin
      concentration is significantly higher in TP when compared to MP, however when
      compared, its clinical use as a diagnostic marker is not valuable as ADA.

PMID- 17531217
TI  - Neuro-fuzzy classification of prostate cancer using NEFCLASS-J.
AB  - Medical diagnosis has been the most proper area for the implementations of
      artificial intelligence for approximately 20 years. In this paper, a new approach
      based on neuro-fuzzy classification (NEFCLASS) tool has been presented to
      classify prostate cancer. The tool has the features of batch learning, automatic
      cross validation, automatic determination of the rule base size, and handling of
      missing values to increase its interpretability. We have investigated how good
      medical data analysis could be done with NEFCLASS-J, and what effects selected
      parameters have on classifier performances. Medical data were obtained from
      patients with real prostate cancer and benign prostatic hyperplasia (BPH). The
      reason for the selection of these two illnesses was the fact that their symptoms
      are very similar yet their differentiation is very crucial. The results showed
      that, for creating high performance of classifier appropriate for the data used,
      firstly it is necessary to decide well on the membership type and the number of
      fuzzy sets and then validation procedure. After a good classifier has been found,
      other parameters should be investigated to improve this classifier. In the light
      of this study, we can present a foresight for the diagnosis of the patients with
      prostate cancer or BPH.

PMID- 17531218
TI  - A transgene-assisted genetic screen identifies essential regulators of vascular
      development in vertebrate embryos.
AB  - Formation of a functional vasculature during mammalian development is essential
      for embryonic survival. In addition, imbalance in blood vessel growth contributes
      to the pathogenesis of numerous disorders. Most of our understanding of vascular
      development and blood vessel growth comes from investigating the Vegf signaling
      pathway as well as the recent observation that molecules involved in axon
      guidance also regulate vascular patterning. In order to take an unbiased, yet
      focused, approach to identify novel genes regulating vascular development, we
      performed a three-step ENU mutagenesis screen in zebrafish. We first screened
      live embryos visually, evaluating blood flow in the main trunk vessels, which
      form by vasculogenesis, and the intersomitic vessels, which form by angiogenesis.
      Embryos that displayed reduced or absent circulation were fixed and stained for
      endogenous alkaline phosphatase activity to reveal blood vessel morphology. All
      putative mutants were then crossed into the Tg(flk1:EGFP)(s843) transgenic
      background to facilitate detailed examination of endothelial cells in live and
      fixed embryos. We screened 4015 genomes and identified 30 mutations affecting
      various aspects of vascular development. Specifically, we identified 3 genes (or
      loci) that regulate the specification and/or differentiation of endothelial
      cells, 8 genes that regulate vascular tube and lumen formation, 8 genes that
      regulate vascular patterning, and 11 genes that regulate vascular remodeling,
      integrity and maintenance. Only 4 of these genes had previously been associated
      with vascular development in zebrafish illustrating the value of this focused
      screen. The analysis of the newly defined loci should lead to a greater
      understanding of vascular development and possibly provide new drug targets to
      treat the numerous pathologies associated with dysregulated blood vessel growth.

PMID- 17531219
TI  - Aloe emodin inhibits the cytotoxic action of tumor necrosis factor.
AB  - We demonstrate the capacity of an herbal anthraquinone aloe emodin to reduce the
      cytotoxicity of the proinflammatory cytokine tumor necrosis factor (TNF) towards
      L929 mouse fibrosarcoma and U251 human glioma cell lines. Aloe emodin inhibited
      both TNF-induced cell necrosis and apoptosis, but it did not reduce cell death
      induced by UV radiation or hydrogen peroxide. Aloe emodin inhibited both basal
      and TNF-triggered activation of extracellular signal-regulated kinase (ERK), and
      a selective blockade of ERK activation mimicked the cytoprotective action of the
      drug. On the other hand, aloe emodin did not affect TNF-induced activation of p38
      mitogen-activated protein kinase or generation of reactive oxygen species. The
      combination of aloe emodin and TNF caused an intracellular appearance of
      acidified autophagic vesicles, and the inhibition of autophagy with bafilomycin
      or 3-methyladenine efficiently blocked the cytoprotective action of aloe emodin.
      These data indicate that aloe emodin could prevent TNF-triggered cell death
      through mechanisms involving induction of autophagy and blockade of ERK
      activation.

PMID- 17531220
TI  - Coagulation factor Xa drives tumor cells into apoptosis through BH3-only protein
      Bim up-regulation.
AB  - Coagulation Factor (F)Xa is a serine protease that plays a crucial role during
      blood coagulation by converting prothrombin into active thrombin. Recently,
      however, it emerged that besides this role in coagulation, FXa induces
      intracellular signaling leading to different cellular effects. Here, we show that
      coagulation factor (F)Xa drives tumor cells of epithelial origin, but not
      endothelial cells or monocytes, into apoptosis, whereas it even enhances
      fibroblast survival. FXa signals through the protease activated receptor (PAR)-1
      to activate extracellular-signal regulated kinase (ERK) 1/2 and p38. This
      activation is associated with phosphorylation of the transcription factor CREB,
      and in tumor cells with up-regulation of the BH3-only pro-apoptotic protein Bim,
      leading to caspase-3 cleavage, the main hallmark of apoptosis. Transfection of
      tumor cells with dominant negative forms of CREB or siRNA for either PAR-1, Bim,
      ERK1 and/or p38 inhibited the pro-apoptotic effect of FXa. In fibroblasts, FXa
      induced PAR-1 activation leads to down-regulation of Bim and pre-treatment with
      PAR-1 or Bim siRNA abolishes proliferation. We thus provide evidence that beyond
      its role in blood coagulation, FXa plays a key role in cellular processes in
      which Bim is the central player in determining cell survival.

PMID- 17531221
TI  - Diseases of epidermal keratins and their linker proteins.
AB  - Epidermal keratins, a diverse group of structural proteins, form intermediate
      filament networks responsible for the structural integrity of keratinocytes. The
      networks extend from the nucleus of the epidermal cells to the plasma membrane
      where the keratins attach to linker proteins which are part of desmosomal and
      hemidesmosomal attachment complexes. The expression of specific keratin genes is
      regulated by differentiation of the epidermal cells within the stratifying
      squamous epithelium. Progress in molecular characterization of the epidermal
      keratins and their linker proteins has formed the basis to identify mutations
      which are associated with distinct cutaneous manifestations in patients with
      genodermatoses. The precise phenotype of each disease apparently reflects the
      spatial level of expression of the mutated genes, as well as the types and
      positions of the mutations and their consequences at mRNA and protein levels.
      Identification of specific mutations in keratinization disorders has provided the
      basis for improved diagnosis and subclassification with prognostic implications
      and has formed the platform for prenatal testing and preimplantation genetic
      diagnosis. Finally, precise knowledge of the mutations is a prerequisite for
      development of gene therapy approaches to counteract, and potentially cure, these
      often devastating and currently intractable diseases.

PMID- 17531222
TI  - Long-term visual prognoses in patients with retinitis pigmentosa: the Ludwig von
      Sallmann lecture.
AB  - Retinitis pigmentosa can be followed over almost its entire course with narrow
      bandpassed, computer averaged cone electroretinograms (ERGs). The long-term rate
      of decline of these responses can be described by an exponential function. A cone
      ERG actuarial table based on 1039 patients and 6553 visits is presented to show
      the estimated number of years for an average patient with a given 30-Hz cone ERG
      amplitude to decline to 0.05 microV (i.e. virtual blindness). The table is based
      on a projected rate of loss of 10% of remaining cone ERG amplitude per year for
      those not on treatment and 8.3% per year for those on treatment with vitamin A
      palmitate 15,000 IU/day. The table can be used to provide an estimate of the
      average long-term visual prognosis from a single visit; more precise estimates
      for a specific patient require several additional visits over 2- to 3-year
      intervals. Evidence is presented to support the idea that patients with a
      projected cone amplitude of 3.5 microV or greater at age 40 (about 25% of our
      patient population with typical retinitis pigmentosa) would be expected, on
      average, to retain some useful vision for their entire lives without treatment.
      Knowledge of the amount of remaining cone function in the ERG often reduces
      patient anxiety and helps patients plan for their future.

PMID- 17531223
TI  - Exposure of human corneal epithelial cells to contact lenses in vitro suppresses
      the upregulation of human beta-defensin-2 in response to antigens of Pseudomonas
      aeruginosa.
AB  - Bacterial keratitis is a sight-threatening complication of contact lens wear, and
      Pseudomonas aeruginosa is a commonly isolated pathogen. The mechanisms by which
      lenses predispose the cornea to P. aeruginosa infection are unknown. Corneal
      epithelial cells express numerous innate defenses, some of which have
      bactericidal effects against P. aeruginosa. One of these is human beta-defensin-2
      (hBD-2), which is upregulated in response to lipopolysaccharide or flagellin
      antigens. We hypothesized that prior exposure of corneal epithelia to a contact
      lens would interfere with upregulation of hBD-2 in response to P. aeruginosa. A
      novel in vitro model was used in which cultured human corneal epithelial cells
      were exposed to a hydrophilic contact lens for up to 3.5 days prior to challenge
      with a culture supernatant of P. aeruginosa antigens for 6h. Without prior lens
      exposure, the supernatant caused >2-fold upregulation of hBD-2 mRNA message and
      expression of hBD-2 peptide. Prior contact lens exposure blocked this
      upregulation without obvious effects on cell health. Western immunoblot and
      luciferase reporter studies showed that Pseudomonas-induced hBD-2 upregulation
      involved MyD88, c-Jun N-terminal kinase and both AP-1 and NF-kappaB transcription
      factors. Contact lenses did not affect surface expression of Toll-like receptor
      2, -4 or -5, but did block antigen activation of AP-1, but not NF-kappaB,
      transcription factors. These data show that contact lenses can interfere with
      epithelial defense responses to bacterial antigens in vitro, and if translated in
      vivo, could help predispose the cornea to infection.

PMID- 17531224
TI  - Time course of changes in pyridoxal 5'-phosphate (vitamin B6 active form) and its
      neuroprotection in experimental ischemic damage.
AB  - In the present study, we investigated ischemia-induced changes of pyridoxal 5'
      phosphate synthesizing enzyme and degrading enzyme and neuroprotective effects
      and roles of pyridoxal 5'-phosphate against ischemic damage in the gerbil
      hippocampal CA1 region. Pyridoxal 5'-phosphate oxidase and pyridoxal phosphate
      phosphatase immunoreactivities were changed in neurons up to 2 days after
      ischemia, while 4 days after ischemia their immunoreactivities were expressed in
      astrocytes. Pyridoxal 5'-phosphate oxidase immunoreactivity and its protein level
      were highest 12 h after ischemia, while those in pyridoxal phosphate phosphatase
      were highest 2 days after ischemia. Total activities of these enzymes were
      changed after ischemia, but specific activities of the enzymes were not altered.
      Treatment with pyridoxal 5'-phosphate into brains (4 microg/5 microl, i.c.v.) at
      30 min before transient ischemia protected about 80% of CA1 pyramidal cells 4
      days after ischemia and induced elevation of glutamic acid decarboxylase 67
      immunoreactivity in the CA1 region. However, pyridoxal 5'-phosphate treatment
      into ischemic brains decreased GABA transaminase immunoreactivity in the CA1
      region after ischemia. These results indicate that pyridoxal 5'-phosphate may be
      associated with the inhibitory discharge of GABA in the hippocampal CA1 neurons,
      and the increased level of GABA may protect hippocampal CA1 pyramidal cells from
      ischemic damage.

PMID- 17531225
TI  - Intervention of geminiviral replication in yeast by ribozyme mediated
      downregulation of its Rep protein.
AB  - Geminiviruses pose serious threat to many economically important crops such as
      mungbean, tomato, cotton, etc. To devise a specific antiviral strategy at the
      viral DNA replication level, a hammerhead ribozyme was directed against the mRNA
      of the replication initiator protein (Rep). Rep is the most important viral
      protein for the DNA replication of the Mungbean yellow mosaic India virus
      (MYMIV), a member of the Geminiviridae family. The ribozyme showed approximately
      33% cleavage activity on synthetic rep transcript within 1h under in vitro
      conditions, whereas the mutant ribozyme, designed to lack the catalytic activity
      but target the same site, showed no cleavage. The in vivo efficiency of ribozyme
      was evaluated in Saccharomyces cerevisiae as it can act as a surrogate host for
      replication of the MYMIV-DNA and lacks RNAi machinery. In the presence of the
      ribozyme, growth of the yeast cells that are dependent on geminiviral replication
      was inhibited by 30% and cellular generation time was increased by 2h. The RT-PCR
      analysis showed a maximum of about 50% reduction in the rep mRNA level in
      presence of the ribozyme compared to its noncatalytic mutant control. About 65%
      decrease in geminiviral DNA replication was observed due to the downregulation of
      replication initiator protein by the ribozyme. These results raise the
      possibility of engineering resistance to geminiviruses employing the ribozyme
      approach.

PMID- 17531226
TI  - Interaction of the Coxsackie and adenovirus receptor (CAR) with the cytoskeleton:
      binding to actin.
AB  - The Coxsackie and adenovirus receptor (CAR) is a cell adhesion molecule that is
      highly expressed in the developing brain. CAR is enriched in growth cone
      particles (GCP) after subcellular fractionation. In GCP, we identified actin as
      an interaction partner of the cytoplasmic domain of CAR. In vivo, actin and CAR
      co-immunoprecipitate and co-localize. In vitro, the binding is direct, with a
      K(d) of approximately 2.6 microM, and leads to actin bundling. We previously
      demonstrated that CAR interacts with microtubules. These data suggest a role for
      CAR in processes requiring dynamic reorganization of the cytoskeleton such as
      neurite outgrowth and cell migration.

PMID- 17531227
TI  - The IGF-I splice variant MGF increases progenitor cells in ALS, dystrophic, and
      normal muscle.
AB  - The effects of muscle splice variants of insulin-like growth factor I (IGF-I) on
      proliferation and differentiation were studied in human primary muscle cell
      cultures from healthy subjects as well as from muscular dystrophy and ALS
      patients. Although the initial numbers of mononucleated progenitor cells
      expressing desmin were lower in diseased muscle, the E domain peptide of IGF-IEc
      (MGF) significantly increased the numbers of progenitor cells in healthy and
      diseased muscle. IGF-I significantly enhances myogenic differentiation whereas
      MGF E peptide blocks this pathway, resulting in an increased progenitor (stem)
      cell pool and thus potentially facilitating repair and maintenance of this
      postmitotic tissue.

PMID- 17531228
TI  - Automated cryoelectron microscopy of "single particles" applied to the 26S
      proteasome.
AB  - The 26S proteasome is a large molecular machine with a central role in
      intracellular protein degradation in eukaryotes. The 2.5 MDa complex, which is
      built from two copies each of more than 30 different subunits, is labile and
      prone to dissociation into subcomplexes. Hence it is difficult if not impossible,
      to obtain structurally homogeneous preparations and, as a consequence, it is very
      cumbersome to obtain large numbers of images of the holocomplex. In this
      communication, we describe an automated procedure for the acquisition of large
      data sets of cryoelectron micrographs. The application of this procedure to the
      26S proteasome from Drosophila has allowed us to determine the three-dimensional
      structure of the complex to a resolution of 2.9 nm and the prospects for further
      improvements are good.

PMID- 17531229
TI  - In vitro RNA editing in plant mitochondria does not require added energy.
AB  - RNA editing in flowering plant mitochondria is investigated by in vitro assays.
      These cauliflower mitochondrial lysates require added NTP or dNTP. We have now
      resolved the reason for this requirement to be the inhibition of the RNA binding
      activity of the glutamate dehydrogenases (GDH). Both GDH1 and GDH2 were
      identified in RNA-protein cross-links. The inhibition of in vitro RNA editing by
      GDH is confirmed by the ability of the GDH-specific herbicide phosphinothricin to
      substitute for NTP. NADH and NADPH, but not NAD or NADP, can also replace NTP,
      suggesting that the NAD(P)H-binding-pocket configuration of the GDH contacts the
      RNA. RNA editing in plant mitochondria is thus intrinsically independent of added
      energy in the form of NTP.

PMID- 17531230
TI  - Assessing the role of endometrial alteration among obese patients undergoing
      assisted reproduction.
AB  - Obesity seems to exert a small but important extraovarian effect that may
      influence cycle outcome during assisted reproduction. Future investigation should
      focus on elucidating whether the endometrium is truly responsible for this
      deficit, and if it is, determining the mechanisms involved.

PMID- 17531231
TI  - Human blastocyst morphological quality is significantly improved in embryos
      classified as fast on day 3 (>or=10 cells), bringing into question current
      embryological dogma.
AB  - OBJECTIVE: To evaluate developmental potential of fast cleaving day 3 embryos.
      DESIGN: Retrospective analysis. SETTING: Academic reproductive center.
      PATIENT(S): Three thousand five hundred twenty-nine embryos. INTERVENTION(S): Day
      3 embryos were classified according to cell number: slow cleaving: <or=6 cells,
      intermediate cleaving: 7-9 cells, and fast cleaving: >or=10 cells, and further
      evaluated on day 5. The preimplantation genetic diagnosis (PGD) results of 43
      fast cleaving embryos were correlated to blastocyst formation. Clinical outcomes
      of transfers involving only fast cleaving embryos (n = 4) were evaluated. MAIN
      OUTCOME MEASURE(S): Blastocyst morphology correlated to day 3 blastomere number.
      Relationship between euploidy and blastocyst formation of fast cleaving embryos.
      Implantation, pregnancy (PR), and birth rates resulting from fast embryo
      transfers. RESULT(S): Blastocyst formation rate was significantly greater in the
      intermediate cleaving (72.7%) and fast cleaving (54.2%) groups when compared to
      the slow cleaving group (38%). Highest quality blastocysts were formed
      significantly more often in the fast cleaving group. Twenty fast cleaving embryos
      that underwent PGD, formed blastocysts, of which 45% (9/20) were diagnosed as
      euploid. Aneuploidy was diagnosed in 82.6% (19/23) of arrested embryos. A 50%
      implantation and 100% PR and birth rate were achieved with embryo transfers
      involving fast cleaving embryos. CONCLUSION(S): Fast cleaving embryos not only
      reach the blastocyst stage at a similar rate to intermediate cleaving embryos,
      but also exceed morphological quality criteria on day 5. Fast cleaving embryo
      transfers demonstrated a high clinical potential.

PMID- 17531232
TI  - Absence of endometrium as a cause of primary amenorrhea.
AB  - OBJECTIVE: To describe congenital endometrial absence. DESIGN: Case report.
      SETTING: University hospital. PATIENT(S): A 32-year-old woman presented with
      primary amenorrhea and infertility. Hormone analysis, physical and gynecologic
      examinations, transvaginal ultrasonography, and karyotype analysis were normal.
      INTERVENTION(S): Progesterone challenge test, laparoscopy, hysteroscopy were
      performed, and hysteroscopic biopsies were obtained from the uterine cavity. MAIN
      OUTCOME MEASURE(S): Presence of endometrium, menstruation. RESULT(S): The
      progesterone challenge test was negative. Laparoscopy revealed normal pelvic
      structures. Evaluation of biopsies from uterine cavity revealed absence of
      endometrium. CONCLUSION(S): Endometrial absence is a differential diagnosis for
      primary amenorrhea; assessment of the uterine cavity and obtaining biopsy samples
      may help in diagnosis of suspected cases before they undergo assisted
      reproduction and can avoid unnecessary treatment.

PMID- 17531233
TI  - Increased expression of uteroglobin associated with tubal inflammation and
      ectopic pregnancy.
AB  - OBJECTIVE: Evaluation of uteroglobin (UG) expression in the fallopian tube in
      different tubal diseases. DESIGN: The UG was screened and quantified in samples
      of fallopian tubes from patients with salpingitis, hydrosalpinx, and ectopic
      pregnancy by exposing the UG with immunohistochemical techniques. SETTING:
      University hospital and electron microscopy center. PATIENT(S): Women with pelvic
      inflammatory disease (PID) and complicated tubal ectopic pregnancy consulting for
      medical care. INTERVENTION(S): Salpingectomy. MAIN OUTCOME MEASURE(S): Tubal
      tissues were collected and examined using regular pathologic techniques. The UG
      immunoreactivity in the tubal epithelium was also assessed. RESULT(S): Fallopian
      tube epithelium displayed an increased UG expression in patients with PID and
      complicated tubal pregnancy compared with control patients. CONCLUSION(S):
      Uteroglobin is present in the human fallopian tube as a secretory protein and
      appears to be involved in immunosuppressive responses in the fallopian tube.

PMID- 17531234
TI  - Expression and comparison of gap junction protein connexin 37 in granulosa cells
      aspirates from follicles of poor responder and nonpoor responder patients.
AB  - OBJECTIVE: To localize gap junction protein connexin 37 (Cx37) in granulosa cells
      obtained from aspiration of follicles, and to compare differences between poor
      responder and nonpoor responder patients in assisted reproductive technology.
      DESIGN: Prospective clinical study. SETTING: IVF unit of a university hospital.
      PATIENT(S): Seventy patients with various causes of infertility, undergoing an
      IVF treatment. INTERVENTION(S): Controlled ovarian hyperstimulation, serum
      hormone level measurements, ultrasonography scanning of ovarian follicles, oocyte
      retrieval after hCG administration and embryo transfer. MAIN OUTCOME MEASURE(S):
      Outcome of the IVF treatment and expression rate of Cx37 in granulosa cells.
      RESULT(S): Connexin 37 was expressed in the granulosa cells of all the patients.
      Connexin 37 rate in granulosa cells in the poor responder group was 81.32 +/-
      35.86% (distribution: 2.95%-99.9%), while it was 88.98 +/- 23.73% (distribution:
      6.30%-100.00%) in the nonpoor responder group. Connexin 37 rates between the two
      groups were not significantly different. CONCLUSION(S): Connexin 37 is expressed
      in the granulosa layer of follicles in the human ovary, and expression of Cx37 in
      granulosa cells was not different between poor responder and nonpoor responder
      patients.

PMID- 17531235
TI  - High incidence of Y-chromosome microdeletions in gonadal tissues from patients
      with 45,X/46,XY gonadal dysgenesis.
AB  - A higher incidence of Y-chromosome microdeletions was found on gonadal DNA than
      on peripheral blood lymphocyte DNA and on streak gonads than on dysgenetic testis
      in 11 patients with 45,X/46,XY gonadal dysgenesis. It is probable that an
      association between Y-chromosome microdeletions and severity of the phenotype in
      45,X/46,XY patients exists.

PMID- 17531236
TI  - Peroral direct cholangioscopic argon plasma coagulation by using an ultraslim
      upper endoscope for recurrent hepatoma with intraductal nodular tumor growth
      (with videos).

PMID- 17531237
TI  - Submucosal endoscopy: a novel approach to en bloc endoscopic mucosal resection
      (with videos).
AB  - BACKGROUND: The submucosal layer is of eminent importance for endoscopic mucosal
      resection (EMR) in the GI tract. OBJECTIVE: Development of submucosal endoscopy,
      which allows diagnostic and therapeutic endoscopy of the submucosal space (SS) in
      the esophagus. DESIGN: Acute experiments in a live porcine model. INTERVENTIONS:
      An area in the esophagus was marked with a diathermic probe to define a mucosal
      piece for resection. After local infiltration, a 1- to 2-cm transverse incision
      was performed 1 to 2 cm proximal and distal of these margins. We entered the SS
      with a flexible small-caliber videoendoscope through the proximal incision and
      dissected the fibrous submucosal connective tissue in a longitudinal direction
      with a blunt forceps. For EMR, the lifted mucosa was subsequently separated by
      use of an insulated-tip hook needle-knife. MAIN OUTCOME MEASUREMENTS: En bloc
      resection of prespecified mucosal areas. RESULTS: A total of 15 mucosal pieces
      were resected in 4 pigs. The size of the resected pieces varied from 1.6 cm x 0.9
      cm to 7.4 cm x 1.7 cm ex vivo. In a fifth pig, 2 circular mucosectomies (lengths
      3.0 cm and 1.6 cm) were done. All mucosal pieces could be completely resected en
      bloc. The endoscopic view in the SS was excellent. There were no procedure
      related complications. LIMITATIONS: The method has not yet been evaluated in
      humans. CONCLUSIONS: Entering the SS for submucosal endoscopy is a novel,
      innovative, and practicable method for the dissection of mucosal neoplastic
      lesions. We demonstrated that mucosal areas of various sizes could be resected en
      bloc without complications.

PMID- 17531238
TI  - Management and reconstruction of pelvic instability after emergency
      symphysiotomy.

PMID- 17531239
TI  - Complications of three sacrospinous ligament fixation techniques.
AB  - OBJECTIVES: To compare the complications of three techniques used to pass the
      suture through the sacrospinous ligament when performing sacrospinous ligament
      fixation (SSLF): (1) the standard needle driver with direct visualization; (2)
      the Deschamps ligature carrier by palpation; and (3) the Miya hook ligature
      carrier by palpation. MATERIALS AND METHODS: A retrospective chart review of 240
      patients undergoing SSLF was performed. A standard needle driver with direct
      visualization was used for 46 patients; the Deschamps ligature carrier was used
      for 173, and the Miya hook for 21 patients. Intraoperative and postoperative
      complications were compared between the groups. RESULTS: Twelve women (5%) had
      intraoperative and forty women (17%) had postoperative complications suspected
      directly from the suture placement. There was no statistically significant
      difference in the rate of total intraoperative complications among the three
      groups. The proportion of patients with postoperative complications that were
      felt to be directly related to the suture passage technique was significantly
      higher in the Deschamps group compared to the direct visualization group (18% vs
      2%, P=0.002). CONCLUSION: Passing the suture through the sacrospinous ligament
      under direct visualization may result in less intra and postoperative
      complications.

PMID- 17531240
TI  - How adaptive is parasite species diversity?
AB  - Has species diversity in parasites evolved as a by-product of adaptive
      diversification driven by competition for limited resources? Or is it a result of
      gradual genetic drift in isolation? One can move closer to answering these
      questions by evaluating the ubiquity of host switching, the key stage of adaptive
      diversification. Studies dealing with evolutionary role of host switching suggest
      that this process is extremely common in the wild, thus pointing at adaptive
      nature of parasite species diversity. However, most of these studies are focused
      on the evidence that may or may not have emerged as a consequence of host
      switching, - an approach potentially associated with a degree of uncertainty.
      After an overview of the data I am making an attempt to get a clearer view on
      host switching by focusing on factors that cause this phenomenon. In particular,
      I review theoretical work and field observations in order to identify the type of
      genetic host-use variance and the type of dispersal that underpin host switching.
      I show that host switching is likely to require generalist modifier alleles which
      increase the host range of individual genotypes and is likely to be promoted by
      wave-like patterns of dispersal. Both factors appear to be common in parasites. I
      conclude by outlining key areas for future research, including: (i) direct
      testing for divergence with gene flow, the main "footprint" of adaptive
      speciation; (ii) investigating the association between demography, dispersal
      potential and the potential to colonise novel habitats; and (iii) determining the
      genetic mechanisms underpinning host range variance in parasites.

PMID- 17531241
TI  - HIV protease inhibitors increase TNF-alpha and IL-6 expression in macrophages:
      involvement of the RNA-binding protein HuR.
AB  - HIV protease inhibitors (PIs) have been associated with the serious Metabolic
      Syndrome, which is the major risk factor of atherosclerotic cardiovascular
      disease. Atherosclerosis is widely considered to be a chronic inflammatory
      disease. Macrophages are the most prominent cell type present in atherosclerotic
      lesions and play essential roles in both early lesion development and late lesion
      complications. We previously reported that HIV PIs induced accumulation of
      intracellular free cholesterol and lipids, decreased endoplasmic reticulum (ER)
      calcium stores, activated the unfolded protein response (UPR), significantly
      increased apoptosis, and promoted foam cell formation in macrophages. HIV PI
      induced ER stress and subsequent activation of the UPR, represents an important
      cell signaling mechanism of HIV PI-induced metabolic syndromes. Here we show that
      all HIV PIs, except amprenavir, increased expression of the major mediators of
      inflammatory response, TNF-alpha and IL-6, to varying degrees. Furthermore, we
      show that the RNA-binding protein, HuR, plays an important role in HIV PI-induced
      expression of TNF-alpha and IL-6. Atazanavir increased the cytoplasmic levels of
      HuR and enhanced the binding of HuR to 3'-UTR of TNF-alpha and IL-6. Down
      regulation of HuR expression by siRNA prevented atazanavir-induced increase of
      TNF-alpha and IL-6. These results suggest that HuR might have an impact on
      pathophysiological processes of HIV PI-induced atherosclerosis.

PMID- 17531242
TI  - C-reactive protein induces endothelial cell apoptosis and matrix
      metalloproteinase-9 production in human mononuclear cells: Implications for the
      destabilization of atherosclerotic plaque.
AB  - C-reactive protein (CRP) has been suggested to directly induce the inflammatory
      response leading to the progression of atherosclerosis. However, recent in vitro
      studies raised the possibility that the effects of CRP are caused by biologically
      active contaminants such as sodium azide and endotoxin. In this study, we tested
      whether azide- and endotoxin-free CRP induces endothelial cell apoptosis and
      production of proinflammatory mediators. In human endothelial cells, CRP
      significantly inhibited cell proliferation and increased endothelial cell
      apoptosis evaluated by terminal deoxynucleotidyltransferase-mediated dUTP nick
      end labeling and caspase-3 activity assay, which is reversed by a function
      blocking antibody to Fc gamma RIIIB by 78%. Western blot analysis showed that CRP
      significantly attenuated flow-mediated activation of Akt, a key molecule for
      endothelial cell survival pathways. In human mononuclear cells, CRP-induced
      production of tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1
      beta), and matrix metalloproteinase-9 (MMP-9) in a concentration-dependent
      manner. This CRP-induced MMP-9 production was significantly inhibited by function
      blocking antibodies to TNF-alpha, IL-1 beta, and Fc gamma RIIA. These findings
      suggest that CRP itself induces endothelial cell apoptosis and production of
      proinflammatory mediators. Because endothelial cell apoptosis and MMP-9
      production are critical for the destabilization of atherosclerotic plaque, this
      study may provide insight into a role of CRP in the development of plaque
      rupture.

PMID- 17531243
TI  - Wine, research and cardiovascular disease: instructions for use.
AB  - The results of studies on the role of appropriate wine consumption in the
      prevention of cardiovascular disease are inconsistent, suggesting that the
      general approach to the issue needs to be revisited before further research is
      conducted. A number of points for consideration are raised: (1) the necessity to
      characterize wine analytically, as the content in important components of wine,
      such as resveratrol, is influenced considerably by regional factors, such as
      climate and local oenological procedures; (2) the bioavailability of the
      components of wine, which appears to be adequate as a broad range of biological
      effects have been documented at low concentrations that can be achieved by
      moderate chronic wine consumption; (3) the lack of importance of wine color, as
      also white wine consumption affords benefit, thanks to its content in the
      antioxidants caffeic acid, tyrosol and hydroxytyrosol, which are also found in
      olive oil; (4) the recommendation by WHO to "investigate the possible protective
      effects of ingredients other than alcohol in alcoholic beverages".

PMID- 17531244
TI  - Characterization and pillaring of a Turkish bentonite (Resadiye).
AB  - The shifts of the SiOSi stretching and the SiOAl and SiOSi bending modes, as well
      as the free silica peak in the IR spectra and the strengthening of the XRD
      reflections due to the quartz and alpha-cristobalite components of the Al
      pillared bentonites (Wyoming and Resadiye), are ascribed to the formation of new
      SiOAl groups of covalent character. The mass losses in the temperature range 150
      700 degrees C correspond to the dehydration and dehydroxylation processes. The
      total mass losses of the Al-pillared bentonites (Wyoming and Resadiye) are close
      to each other at an OH/Al ratio of 2.2, but calcination from 400 to 600 degrees C
      causes the surface area of the latter composite to decrease by 13%.

PMID- 17531245
TI  - Preparation, characterization, and CuX2 and CoX2 (X=Cl-, Br-, ClO-4) adsorption
      behavior of a polyhedral oligomer silsesquioxane functionalized with an organic
      base.
AB  - In this paper we report on the synthesis, characterization, and adsorption
      properties of the first 3-amino-1,2,4-triazole-modified porous silsesquioxane
      (ATPS). The isotherms of adsorption of MX(2) (M=Cu(II), Co(II); X=Cl(-), Br(-),
      ClO(-)(4)) by ATPS were studied in ethanol and aqueous solutions at 298 K. The
      results showed that there is a good fit between the experimental data and the
      Langmuir isotherm. The adsorption capacity in both solvents followed the sequence
      Cu(II)>>Co(II). The lowest adsorption for Co(II) should be related to the largest
      hydration volume, which obstructs the adsorption capacity of the surface, and
      consequently causes a decrease in the number of cations adsorbed. For the salts
      with different anions the sequence was MCl(2)>MBr(2)>M(ClO(4))(2) in both
      solvents. The low affinity for M(ClO(4))(2) toward the solid phase is a
      consequence of the poorer coordination ability of the ClO(-)(4). Adsorptions from
      ethanol solutions were higher than those from aqueous solutions due to the higher
      polarity of water, which can more strongly solvate the solute and the basic sites
      on the surface. The following adsorption capacities (in mmol g(-1)) were
      determined: 0.24 (aq) and 0.84 (eth) for CuCl(2), 0.09 (aq) and 0.16 (eth) for
      CuBr(2), and 0.08 (aq) and 0.11 (eth) for Cu(ClO(4))(2); 0.02 (aq) and 0.07 (eth)
      for CoCl(2), 0.02 (aq) and 0.06 (eth) for CoBr(2), and 0.01 (aq) and 0.05 (eth)
      for Co(ClO(4))(2).

PMID- 17531246
TI  - Capillary condensation in pores with rough walls: a density functional approach.
AB  - The effect of surface roughness of slit-like pore walls on the capillary
      condensation of a spherical particles and short chains is studied. The gas
      molecules interact with the substrate by a Lennard-Jones (9,3) potential. The
      rough layer at each pore wall has a variable thickness and density and consists
      of a disordered quenched matrix of spherical particles. The system is described
      in the framework of a density functional approach and using computer simulations.
      The contribution due to attractive van der Waals interactions between adsorbate
      molecules is described by using first-order mean spherical approximation and mean
      field approximation.

PMID- 17531247
TI  - Growth of highly oriented crystalline polyaniline films by self-organization.
AB  - Silicon substrates with (100) orientation were modified with amino-silane self
      assembled monolayer (SAM) to provide amino (NH(2)) moieties at the substrate
      surface. Self-organization of polyaniline during chemical polymerization, on this
      modified surface, leads to the growth of highly oriented films at the substrate
      polymer interface. The morphology studied using scanning electron microscopy and
      atomic force microscopy revealed the formation of polymer film with well faceted
      pyramidal crystallites. XPS and FTIR spectroscopy were used to analyze the
      chemical structure of the film. X-ray diffraction measurements show the
      crystalline nature of the polyaniline, whose lattice parameters are in agreement
      with the reported values. This study underlines the importance of a SAM in
      deciding the structure and morphology of the deposited polymer.

PMID- 17531248
TI  - Amplitude of ST-segment elevation as a function of the heart rate in patients
      with early repolarization.

PMID- 17531250
TI  - Detection of patients with coronary artery disease using cardiac magnetic field
      mapping at rest.
AB  - We studied the use of cardiac magnetic field mapping to detect patients with CAD
      without subjecting them to stress. Fifty-nine healthy control subjects and 101
      patients with CAD without previous MI were included. The optimal positions for
      detecting CAD were located in the left superior parasternal and in the inferior
      midsternal area. Values for ST slope, ST shift, T peak amplitude, ST-T integral,
      and magnetic field map orientation differed significantly between the 2 groups.
      Three parameters together in a multivariate analysis yielded a sensitivity of 84%
      and a specificity of 83% in distinguishing patients with CAD from control
      subjects. We suggest that cardiac magnetic field mapping is a promising technique
      to identify patients with CAD.

PMID- 17531251
TI  - Bepridil produces prominent bradycardia-dependent QT prolongation in patients
      with structural heart disease.
AB  - The aim of the present study is to elucidate the effect of bepridil on heart rate
      dependent QT prolongation in patients with or without structural heart disease.
      QT intervals and the preceding R-R intervals were randomly measured by 24-hour
      Holter electrocardiogram in 29 patients with symptomatic arrhythmias. The slope
      of the regression curve was used as a marker of bradycardia-dependent QT
      prolongation. The slope was not different in patients without structural heart
      disease (0.34 +/- 0.10) as compared with the apparently normal control subjects
      (0.32 +/- 0.057, n = 29), whereas it was larger than that in patients with
      structural heart disease (0.57 +/- 0.17; P < .01). Steep slopes (>0.43) were
      observed in 11 of the 14 patients with structural heart disease, whereas they
      were observed only in 1 patient without structural heart disease (P < .01). In
      conclusion, we need to pay attention to bradycardia-dependent QT prolongation by
      bepridil, especially when dealing with structural heart disease.

PMID- 17531252
TI  - Interatrial block: a prevalent, widely neglected, and portentous abnormality.

PMID- 17531253
TI  - Low prevalence of atrial fibrillation in community-dwelling Chinese aged 55 years
      or older in Singapore: a population-based study.
AB  - BACKGROUND: The prevalence of atrial fibrillation (AF) in Asian populations
      appears to be lower than that in Western populations according to limited data.
      We conducted a community study to (a) estimate the prevalence of AF in Chinese
      adults aged 55 years or older in Singapore and (b) examine associated risk
      factors. METHODS: We conducted a whole-survey area population screening of 1839
      Chinese residents aged 55 years or older in the southeast region of Singapore
      with a single electrocardiographic recording. We performed structured interviews
      and anthropometric as well as clinical measurements, including blood pressure.
      RESULTS: The estimated overall AF prevalence was 1.5% (95% confidence interval =
      1.1-2.2); specifically, the prevalence was higher in men (2.6%) than in women
      (0.6%) and increased sharply to 5.8% only in individuals aged 80 years or older.
      This latter rate is lower than age-standardized rates in Western populations by
      approximately half and consistent with similarly low prevalence rates reported
      for Korea and China. Of the 26 cases of AF in this study, only 10 were known
      cases; 3 of the 10 patients were receiving anticoagulant therapy, whereas the
      rest were receiving antiplatelet therapy. Atrial fibrillation was significantly
      associated in multivariate analyses with male sex (odds ratio [OR] = 4.10), heart
      failure (OR = 3.11), and stroke (OR = 3.60). CONCLUSIONS: These data add support
      to the view that the prevalence of AF in Asian populations is lower than that in
      Western populations. The observations from these contrasting populations warrant
      attention in future studies.

PMID- 17531254
TI  - Syncope, seizure, or both? An unusual case of complete heart block.
AB  - Syncope and epileptic seizures have common presenting features that make it
      difficult to determine if a patient's collapse is primarily cardiac or
      neurologic. The distinction is blurred further if epileptic neural activity
      provokes cardiac arrhythmias known to cause syncope. We present a case of
      convulsive movements, progressive atrioventricular block, and syncope in a
      patient known to have epilepsy. The history, serial electrocardiographic
      tracings, and other diagnostic tests strongly suggest the ictal bradycardia
      syndrome. The case illustrates interesting aspects of central autonomic function
      and the diagnostic and therapeutic dilemmas of evaluating and treating patients
      who present with this problem.

PMID- 17531255
TI  - High-frequency electrocardiogram analysis in the ability to predict reversible
      perfusion defects during adenosine myocardial perfusion imaging.
AB  - BACKGROUND: A previous study has shown that analysis of high-frequency QRS
      components (HF-QRS) is highly sensitive and reasonably specific for detecting
      reversible perfusion defects on adenosine myocardial perfusion imaging (MPI)
      scans. The purpose of the present study was to try to reproduce those findings.
      METHODS: Twelve-lead high-resolution electrocardiogram recordings were obtained
      from 100 patients before (baseline) and during adenosine (99m)Tc-tetrofosmin MPI
      tests. The HF-QRS were analyzed regarding morphology and changes in root mean
      square voltages from before the adenosine infusion to peak infusion. RESULTS: The
      best area under the curve (AUC) was found in supine patients (AUC = 0.736) in a
      combination of morphology and root mean square changes. None of the measurements,
      however, were statistically better than tossing a coin (AUC = 0.5). CONCLUSION:
      Analysis of HF-QRS was not significantly better than tossing a coin for
      determining reversible perfusion defects on MPI scans.

PMID- 17531256
TI  - Proarrhythmic potential of reverse use-dependent drugs.

PMID- 17531257
TI  - Errors in the computerized electrocardiogram interpretation of cardiac rhythm.
AB  - BACKGROUND: More than 100 million computer-interpreted electrocardiograms (ECG-C)
      are obtained annually. However, there are few contemporary published data on the
      accuracy of cardiac rhythm interpretation by this method. PURPOSE: The purpose of
      this study is to determine the accuracy of ECG-C rhythm interpretation in a
      typical patient population. METHODS: We compared the ECG-C rhythm interpretation
      to that of 2 expert overreaders in 2112 randomly selected standard 12-lead ECGs.
      RESULTS: The ECG-C correctly interpreted the rhythm in 1858 and incorrectly
      identified the rhythm in 254 (overall accuracy, 88.0%). Sinus rhythm was
      correctly interpreted in 95.0% of the ECGs (1666/1753) with this rhythm, whereas
      nonsinus rhythms were correctly interpreted with an accuracy of only 53.5%
      (192/359) (P < .0001). The ECG-C interpreted sinus rhythm with a sensitivity of
      95% (confidence interval, 93.8-96.7), specificity of 66.3%, and positive
      predictive value of 93.2%. The ECG-C interpreted nonsinus rhythms with a
      sensitivity of 72%, (confidence interval, 68.7-73.7), a specificity of 93%, and a
      positive predictive value of 59.3%. Of the 254 ECGs that had incorrect rhythm
      interpretation, additional major errors were noted in 137 (54%). CONCLUSIONS: The
      ECG-C demonstrates frequent errors in the interpretation of nonsinus rhythms. In
      addition, incorrect rhythm interpretation by the ECG-C was frequently further
      compounded by additional major inaccuracies. Expert overreading of the ECG
      remains important in clinical settings with a high percentage of nonsinus
      rhythms.

PMID- 17531258
TI  - Transient pathologic Q waves in a case of apical ballooning.

PMID- 17531259
TI  - High prevalence of widened P waves among pediatric patients in 2 separate
      hospitals.
AB  - INTRODUCTION: In adults, P waves of 110 milliseconds or longer are often
      associated with significant disease. In the pediatric population, however,
      cutoffs for P-wave durations are naturally lower but could vary physiologically
      with age because of increasing heart mass. We appraised if age-proportionate
      increase in P-wave duration does indeed occur in both hospitalized infants and
      children and also investigated the prevalence of widened P-wave durations using
      currently accepted "normal" cutoffs (</=70 milliseconds for infants and </=90
      milliseconds for children). METHODS: We consecutively obtained 12-lead
      electrocardiograms of infants and children aged up to 16 years (range, 0.1-16
      years; mean +/- SD, 10.1 +/- 5.2 years; male, 46.9%) who presented through the
      emergency department for nonacute, noncardiac conditions at the Nassau University
      Medical Center (NUMC), East Meadow, NY, and Saint Vincent Hospital (SVH),
      Worcester, MA, from January to May 2006. Electrocardiograms were then evaluated
      for the greatest P-wave duration in every lead to the nearest 10 milliseconds
      using a calibrated magnifying graticule on a blinded, single read. RESULTS: The
      study sample consisted of 96 nonacute pediatric patients: infants and children
      from NUMC (age, 0.1-16 years; mean +/- SD, 9.1 +/- 5.4 years; male, 46.6%) and
      children from SVH (age, 6-16 years; mean +/- SD, 13.1 +/- 2.5 years; male,
      47.8%). Prolonged P waves longer than 70 milliseconds were present in 3 (23%) of
      the 13 NUMC infants, whereas prolonged P waves longer than 90 milliseconds were
      observed in 16 (27%) of the 60 NUMC children and 7 (30%) of the 23 SVH children.
      Linear regression analysis revealed that age was the sole predictor of increasing
      P-wave durations on any lead [age = -15.33 + 0.30 (P-wave duration
      [milliseconds]); r(2) = 0.44]. Moreover, there was a significant increase in P
      wave duration for patients aged 10 years or older, where a notable step-up in
      such measurements was observed. CONCLUSION: P-wave duration is significantly
      associated with age among hospitalized children as well as infants, where
      particular increase occurs at 10 years of age or older. General pediatricians
      and, more importantly, pediatric cardiologists, need to be more vigilant in using
      appropriate age-based P-wave cutoffs when assessing interatrial conduction in
      this population.

PMID- 17531260
TI  - Atrial double potential associated with electrical connection between the
      coronary sinus musculature and the left atrium in a patient with Wolff-Parkinson
      White syndrome.
AB  - We reported a case of Wolff-Parkinson-White syndrome with atrial double potential
      in coronary sinus (CS) electrograms during paroxysmal supraventricular
      tachycardia and ventricular pacing. The first component was low in frequency, and
      its timing was the same as atrial potential recorded by ablation catheter above
      the mitral annulus by transseptal approach; the second portion was high in
      frequency. The accessory pathway conduction was completely eliminated after
      ablation on the atrial site. We speculated that the discrete musculature
      connection between left atrium and CS was responsible for the pattern of double
      potential activation in the CS electrograms during paroxysmal supraventricular
      tachycardia and ventricular pacing.

PMID- 17531261
TI  - Three-colour flow cytometric method to measure antibody-dependent tumour cell
      killing by cytotoxicity and phagocytosis.
AB  - We have developed a three-colour flow cytometric method to assay the
      contributions of cytotoxicity and phagocytosis to antibody-dependent cell
      mediated tumour cell killing. In this assay, tumour target cells are pre-labelled
      with CFSE, and mixed with effector cells and a tumour antigen-specific monoclonal
      antibody. After incubation of the cells with the antibody, effector cells are
      labelled with PE and dead cells with PI. Using flow cytometry, dead and
      phagocytosed tumour cells can be quickly and easily counted and the numbers
      summed to determine the total number of killed cells. One can thereby measure the
      phagocytic aspect of antibody-dependent cell-mediated tumour cell killing,
      otherwise only revealed by microscopic examination. The failure to detect
      phagocytosed, in addition to live and dead target cells, by standard assays may
      result in an underestimation of tumour cell killing and hence the potential of an
      antibody for immunotherapy of cancer. We illustrate the new method by analysing
      human monocyte-mediated cytotoxic and phagocytic cell killing of IGROV1 ovarian
      tumour cells by the ovarian tumour antigen-specific anti-folate binding protein
      monoclonal antibody, MOv18 IgE.

PMID- 17531262
TI  - Kruppel-like Factors (KLFs) in muscle biology.
AB  - The Kruppel-like Factor (KLF) family of zinc-finger transcription factors are
      critical regulators of cell differentiation, phenotypic modulation and
      physiologic function. An emerging body of evidence implicates an important role
      for these factors in cardiovascular biology, however, the role of KLFs in muscle
      biology is only beginning to be understood. This article reviews the published
      data describing the role of KLFs in the heart, smooth muscle, and skeletal muscle
      and highlights the importance of these factors in cardiovascular development,
      physiology and disease pathobiology.

PMID- 17531263
TI  - A single hERG mutation underlying a spectrum of acquired and congenital long QT
      syndrome phenotypes.
AB  - The long QT syndrome (LQTS) is a multi-factorial disorder that predisposes to
      life-threatening arrhythmias. Both hereditary and acquired subforms have been
      identified. Here, we present clinical and biophysical evidence that the hERG
      mutation c.1039 C>T (p.Pro347Ser or P347S) is responsible for both the acquired
      and the congenital phenotype. In one case the genotype remained silent for years
      until the administration of several QT-prolonging drugs resulted into a full
      blown phenotype, that was reversible upon cessation of these compounds. On the
      other hand the mutation was responsible for a symptomatic congenital LQTS in a
      Dutch family, displaying a substantial heterogeneity of the clinical symptoms.
      Biophysical characterization of the p.Pro347Ser potassium channels using whole
      cell patch clamp experiments revealed a novel pathogenic mechanism of reciprocal
      changes in the inactivation kinetics combined with a dominant-negative reduction
      of the functional expression in the heterozygous situation, yielding a modest
      genetic predisposition for LQTS. Our data show that in the context of the multi
      factorial aetiology underlying LQTS a modest reduction of the repolarizing power
      can give rise to a spectrum of phenotypes originating from one mutation. This
      observation increases the complexity of genotype-phenotype correlations in more
      lenient manifestations of the disease and underscores the difficulty of
      predicting the expressivity of the LQTS especially for mutations with a more
      subtle impact such as p.Pro347Ser.

PMID- 17531264
TI  - Substrate and product complexes of Escherichia coli adenylosuccinate lyase
      provide new insights into the enzymatic mechanism.
AB  - Adenylosuccinate lyase (ADL) catalyzes the breakdown of 5-aminoimidazole- (N
      succinylocarboxamide) ribotide (SAICAR) to 5-aminoimidazole-4-carboxamide
      ribotide (AICAR) and fumarate, and of adenylosuccinate (ADS) to adenosine
      monophosphate (AMP) and fumarate in the de novo purine biosynthetic pathway. ADL
      belongs to the argininosuccinate lyase (ASL)/fumarase C superfamily of enzymes.
      Members of this family share several common features including: a mainly alpha
      helical, homotetrameric structure; three regions of highly conserved amino acid
      residues; and a general acid-base catalytic mechanism with the overall beta
      elimination of fumarate as a product. The crystal structures of wild-type
      Escherichia coli ADL (ec-ADL), and mutant-substrate (H171A-ADS) and -product
      (H171N-AMP.FUM) complexes have been determined to 2.0, 1.85, and 2.0 A
      resolution, respectively. The H171A-ADS and H171N-AMP.FUM structures provide the
      first detailed picture of the ADL active site, and have enabled the precise
      identification of substrate binding and putative catalytic residues. Contrary to
      previous suggestions, the ec-ADL structures implicate S295 and H171 in base and
      acid catalysis, respectively. Furthermore, structural alignments of ec-ADL with
      other superfamily members suggest for the first time a large conformational
      movement of the flexible C3 loop (residues 287-303) in ec-ADL upon substrate
      binding and catalysis, resulting in its closure over the active site. This loop
      movement has been observed in other superfamily enzymes, and has been proposed to
      be essential for catalysis. The ADL catalytic mechanism is re-examined in light
      of the results presented here.

PMID- 17531265
TI  - The sequence of the RNA primer and the DNA template influence the initiation of
      plus-strand DNA synthesis in hepatitis B virus.
AB  - For hepadnaviruses, the RNA primer for plus-strand DNA synthesis is generated by
      the final RNase H cleavage of the pregenomic RNA at an 11 nt sequence called DR1
      during the synthesis of minus-strand DNA. This RNA primer initiates synthesis at
      one of two distinct sites on the minus-strand DNA template, resulting in two
      different end products; duplex linear DNA or relaxed circular DNA. Duplex linear
      DNA is made when initiation of synthesis occurs at DR1. Relaxed circular DNA, the
      major product, is made when the RNA primer translocates to the sequence
      complementary to DR1, called DR2 before initiation of DNA synthesis. We studied
      the mechanism that determines the site of the final RNase H cleavage in hepatitis
      B virus (HBV). We showed that the sites of the final RNase H cleavage are always
      a fixed number of nucleotides from the 5' end of the pregenomic RNA. This finding
      is similar to what was found previously for duck hepatitis B virus (DHBV), and
      suggests that all hepadnaviruses use a similar mechanism. Also, we studied the
      role of complementarity between the RNA primer and the acceptor site at DR2 in
      HBV. By increasing the complementarity, we were able to increase the level of
      priming at DR2 over that seen in the wild-type virus. This finding suggests that
      the level of initiation of plus-strand DNA synthesis at DR2 is sub-maximal for
      wild-type HBV. Finally, we studied the role of the sequence at the 5' end of the
      RNA primer that is outside of the DR sequence. We found that substitutions or
      insertions in this region affected the level of priming at DR1 and DR2.

PMID- 17531266
TI  - Crystal structure of the 16 heme cytochrome from Desulfovibrio gigas: a
      glycosylated protein in a sulphate-reducing bacterium.
AB  - Sulphate-reducing bacteria have a wide variety of periplasmic cytochromes
      involved in electron transfer from the periplasm to the cytoplasm. HmcA is a high
      molecular mass cytochrome of 550 amino acid residues that harbours 16 c-type heme
      groups. We report the crystal structure of HmcA isolated from the periplasm of
      Desulfovibrio gigas. Crystals were grown using polyethylene glycol 8K and zinc
      acetate, and diffracted beyond 2.1 A resolution. A multiple-wavelength anomalous
      dispersion experiment at the iron absorption edge enabled us to obtain good
      quality phases for structure solution and model building. DgHmcA has a V-shape
      architecture, already observed in HmcA isolated from Desulfovibrio vulgaris
      Hildenborough. The presence of an oligosaccharide molecule covalently bound to an
      Asn residue was observed in the electron density maps of DgHmcA and confirmed by
      mass spectrometry. Three modified monosaccharides appear at the highly
      hydrophobic vertex, possibly acting as an anchor of the protein to the
      cytoplasmic membrane.

PMID- 17531267
TI  - Crystal structures of a poplar thioredoxin peroxidase that exhibits the structure
      of glutathione peroxidases: insights into redox-driven conformational changes.
AB  - Glutathione peroxidases (GPXs) are a group of enzymes that regulate the levels of
      reactive oxygen species in cells and tissues, and protect them against oxidative
      damage. Contrary to most of their counterparts in animal cells, the higher plant
      GPX homologues identified so far possess cysteine instead of selenocysteine in
      their active site. Interestingly, the plant GPXs are not dependent on glutathione
      but rather on thioredoxin as their in vitro electron donor. We have determined
      the crystal structures of the reduced and oxidized form of Populus
      trichocarpaxdeltoides GPX5 (PtGPX5), using a selenomethionine derivative. PtGPX5
      exhibits an overall structure similar to that of the known animal GPXs. PtGPX5
      crystallized in the assumed physiological dimeric form, displaying a pseudo ten
      stranded beta sheet core. Comparison of both redox structures indicates that a
      drastic conformational change is necessary to bring the two distant cysteine
      residues together to form an intramolecular disulfide bond. In addition, a
      computer model of a complex of PtGPX5 and its in vitro recycling partner
      thioredoxin h1 is proposed on the basis of the crystal packing of the oxidized
      form enzyme. A possible role of PtGPX5 as a heavy-metal sink is also discussed.

PMID- 17531268
TI  - Trans cooperativity by a split DNA recombinase: the central and catalytic domains
      of bacteriophage lambda integrase cooperate in cleaving DNA substrates when the
      two domains are not covalently linked.
AB  - Site-specific recombinases of the lambda-integrase family recognize and cleave
      their cognate DNA sites through cooperative binding to opposite sides of the DNA
      substrate by a C-terminal catalytic domain and a flexibly linked "core-binding"
      domain; regulation of this cleavage is achieved via the formation of higher-order
      complexes. We report that the core-binding domain of lambda-integrase is able to
      stimulate the activity of the catalytic domain even when the two domains are not
      linked. This trans stimulation is accomplished without significantly increasing
      the affinity of the catalytic domain for its DNA substrate. Moreover, we show
      that mutations in the DNA substrate can abrogate this effect while retaining
      specificity determinants for cleavage. Since the domains do not significantly
      interact directly, this finding implies that trans activation is achieved via the
      DNA substrate in a manner that may be mechanistically important in this and
      similar DNA binding and cleaving enzymes.

PMID- 17531269
TI  - Effects of short term atorvastatin treatment on cerebral hemodynamics in CADASIL.
AB  - BACKGROUND: HMG-CoA-reductase-inhibitors (statins) exhibit pleiotropic beneficial
      effects on the vascular system including induction of endothelial nitric oxide
      synthase (eNOS) expression which is critical for vasodilation. Recent studies
      suggest a beneficial effect of statins on cerebral vasoreactivity in patients
      with cerebral small vessel disease (SVD). CADASIL is a monogenic form of SVD
      caused by mutations in the Notch3 gene. Treatment options are limited and little
      is known about the therapeutic role of statins in CADASIL. METHODS: Twenty-four
      CADASIL subjects were treated with atorvastatin for 8 weeks. Treatment was
      started with 40 mg, followed by a dosage increase to 80 mg after 4 weeks.
      Transcranial Doppler sonography measuring mean flow velocity (MFV) in the middle
      cerebral artery was performed at baseline and the end of the treatment period.
      Vasoreactivity was assessed by hypercapnia and intravenous application of l
      Arginine, which is the substrate for eNOS. RESULTS: There was no significant
      treatment effect on MFV (p=0.5) or cerebral vasoreactivity as assessed by
      hypercapnia (p=0.5) and intravenous l-Arginine (p=0.4) in the overall cohort.
      However, an inverse correlation was found between vasoreactivity at baseline and
      changes of both CO2 and l-Arginine-induced vasomotor response (both p<0.05).
      CONCLUSIONS: Short term treatment with atorvastatin resulted in no significant
      improvement of hemodynamic parameters in the overall cohort of CADASIL subjects.

PMID- 17531270
TI  - Addition of a non-photic component to a light-based mathematical model of the
      human circadian pacemaker.
AB  - Mathematical models have become vital to the study of many biological processes
      in humans due to the complexity of the physiological mechanisms underlying these
      processes and systems. While our current mathematical representation of the human
      circadian pacemaker has proven useful in many experimental situations, it uses as
      input only a direct effect of light on the circadian pacemaker. Although light (a
      photic stimulus) has been shown to be the primary synchronizer of the circadian
      pacemaker across a number of species, studies in both animals and humans have
      confirmed the existence of non-photic effects that also contribute to phase
      shifting and entrainment. We modified our light-based circadian mathematical
      model to reflect evidence from these studies that the sleep-wake cycle and/or
      associated behaviors have a non-photic effect on the circadian pacemaker. In our
      representation, the sleep-wake cycle and its associated behaviors provides a non
      photic drive on the circadian pacemaker that acts both independently and
      concomitantly with light stimuli. Further experiments are required to validate
      fully our model and to understand the exact effect of the sleep-wake cycle as a
      non-photic stimulus for the human circadian pacemaker.

PMID- 17531271
TI  - C-reactive protein: a pentraxin with anti-acetylcholine activity.
AB  - Purified C-reactive protein (CRP) diminished effects of acetylcholine (ACh) on
      the vascular tone and the heart rate of rats in vivo. In vitro CRP inhibited
      breakdown of ACh by acetylcholinesterase (AChE) while did not interact with AChE
      itself. CRP appears to bind ACh. CRP did not modify the cardiovascular effects of
      adenosine, another vasorelaxant. The data suggest that there is a new line of
      cross-talk between the inflammation and cholinergic regulation with CRP acting on
      endothelium via the ACh-dependent pathway.

PMID- 17531272
TI  - Production ecology of agroforestry systems: a minimal mechanistic model and
      analytical derivation of the land equivalent ratio.
AB  - In this paper, the yield and the land equivalent ratio (LER) of a silvo-arable
      agroforestry (SAF) system, containing one tree and one crop species, is analyzed
      analytically using a minimal mechanistic model describing the system dynamics.
      Light competition between tree and crop is considered using light extinction
      functions. The tree leaf area is driven by annual increase in the number of leaf
      bearing shoots with a seasonal cycle of bud burst, leaf expansion and senescence.
      The crop leaf area dynamics is driven by the solar radiation, heat sum and the
      dry matter allocation to the leaves. As a consequence of this, the model consists
      of six state equations expressing the temporal dynamics of: (1) tree biomass; (2)
      tree leaf area; (3) number of shoots per tree; (4) crop biomass; (5) crop leaf
      area index, and (6) heat sum. The main outputs of the model are the growth
      dynamics and final yields of trees and crops. Daily inputs are temperature and
      radiation. Planting densities, initial biomass of tree and crop species and
      growth parameters must be specified. The main parameters are those describing
      light interception, conversion to dry matter and leaf area. Given the crop cover
      and the tree parameters, it is shown that under potential growing conditions the
      land equivalent ratio can be explicitly expressed in terms of these parameters.

PMID- 17531273
TI  - Subcellular characterization of glucose uptake in coronary endothelial cells.
AB  - Despite all the evidence linking glucose toxicity to an increased risk of
      cardiovascular diseases, very little is known about the regulation of glucose
      uptake in endothelial cells. We have previously reported an asymmetric
      distribution of the GLUTs (1-5) and SGLT-1 in en face preparations of rat
      coronary artery endothelia [Gaudreault N., Scriven D.R., Moore E.D., 2004.
      Characterisation of glucose transporters in the intact coronary artery
      endothelium in rats: GLUT-2 upregulated by long-term hyperglycaemia. Diabetologia
      47(12),2081-2092]. We assessed this time, through immunocytochemistry and wide
      field fluorescence microscopy coupled to deconvolution, the presence and
      subcellular distribution of glucose transporters in cultures of human coronary
      artery endothelial cells (HCAECs). HCAECs express GLUT-1 to 5 and SGLT-1, but
      their subcellular distribution lacks the luminal/abluminal asymmetry and the
      proximity to cell-to-cell junctions observed in intact endothelium. To determine
      the impact of the transporters' distribution on intracellular glucose
      accumulation, a fluorescent glucose analog (2-NBDG) was used in conjunction with
      confocal microscopy to monitor uptake in individual cells; the arteries were
      mounted in an arteriograph chamber with physiological flow rates. The uptake in
      both preparations was inhibited by cytochalasin-B and d-glucose and stimulated by
      insulin, but the distribution of the incorporated 2-NBDG mirrored that of the
      transporters. In HCAEC it was distributed throughout the cell and in the intact
      arterial endothelium it was restricted to the narrow cytosolic volume adjacent to
      the cell-to-cell junctions. We suggest that the latter subcellular organization
      and compartmentalization may facilitate transendothelial transport of glucose in
      intact coronary artery.

PMID- 17531274
TI  - Hedonic hunger: a new dimension of appetite?
AB  - An increasing proportion of human food consumption appears to be driven by
      pleasure, not just by the need for calories. In addition to its effects on body
      mass and health, the food environment in affluent societies may be creating an
      appetitive counterpart to the psychological effects of other hedonically-driven
      activities such as drug use and compulsive gambling. This phenomenon is referred
      to here as "hedonic hunger." Animal literature is reviewed indicating that brain
      based homeostatic and hedonic eating motives overlap but are nonetheless
      dissociable. In humans there is evidence that obese individuals prefer and
      consume high palatability foods more than those of normal weight. Among normal
      weight individuals it has long been assumed that the appetitive anomalies
      associated with restrained eating are due to diet-induced challenges to the
      homeostatic system, but we review evidence suggesting that they more likely stem
      from hedonic hunger (i.e., eating less than wanted rather than less than needed).
      Finally, a recently-developed measure (the Power of Food Scale; PFS) of
      individual differences in appetitive responsiveness to rewarding properties of
      the food environment is described. Preliminary evidence indicates that the PFS is
      reliable and valid and is related to clinically-relevant variables such as food
      cravings and binge eating. This measure, combined with environmental
      manipulations of food availability and palatability, may constitute a useful
      approach to studying hedonic hunger.

PMID- 17531275
TI  - Neural network interactions and ingestive behavior control during anorexia.
AB  - Many models have been proposed over the years to explain how motivated feeding
      behavior is controlled. One of the most compelling is based on the original
      concepts of Eliot Stellar whereby sets of interosensory and exterosensory inputs
      converge on a hypothalamic control network that can either stimulate or inhibit
      feeding. These inputs arise from information originating in the blood, the
      viscera, and the telencephalon. In this manner the relative strengths of the
      hypothalamic stimulatory and inhibitory networks at a particular time dictates
      how an animal feeds. Anorexia occurs when the balance within the networks
      consistently favors the restraint of feeding. This article discusses experimental
      evidence supporting a model whereby the increases in plasma osmolality that
      result from drinking hypertonic saline activate pathways projecting to neurons in
      the paraventricular nucleus of the hypothalamus (PVH) and lateral hypothalamic
      area (LHA). These neurons constitute the hypothalamic controller for ingestive
      behavior, and receive a set of afferent inputs from regions of the brain that
      process sensory information that is critical for different aspects of feeding.
      Important sets of inputs arise in the arcuate nucleus, the hindbrain, and in the
      telencephalon. Anorexia is generated in dehydrated animals by way of
      osmosensitive projections to the behavior control neurons in the PVH and LHA,
      rather than by actions on their afferent inputs.

PMID- 17531276
TI  - The sensory circumventricular organs: brain targets for circulating signals
      controlling ingestive behavior.
AB  - Sensory circumventricular organs (CVOs) are specialized areas of the brain that
      lack a normal blood-brain barrier, and therefore are in constant contact with
      signaling molecules circulating in the bloodstream. Neurons of the CVOs are well
      endowed with a wide spectrum of receptors for hormones and other signaling
      molecules, and they have strong connections to hypothalamic and brainstem nuclei.
      Therefore, lying at the blood-brain interface, the sensory CVOs are in a unique
      position of being able to detect and integrate humoral and neural information and
      relay the resulting signals to autonomic control centers of the hypothalamus and
      medulla. This review focuses primarily on the roles played by the sensory CVOs in
      fluid balance and energy metabolism.

PMID- 17531277
TI  - Intestinal nutrients elicit satiation through concomitant activation of CCK(1)
      and 5-HT(3) receptors.
AB  - Previous studies demonstrate that cholecystokinin type-1 (CCK(1)) and serotonin
      type-3 (5-HT(3)) dependent pathways are independently involved in intestinal
      nutrient-induced meal termination. In the current study, we employed selective
      antagonists to investigate the relative contribution of CCK(1) and 5-HT(3)
      receptors in mediating the anorexia produced by duodenal infusion of Polycose or
      Intralipid in rats. Combined administration of 1 mg/kg ondansetron (Ond) and 1
      mg/kg devazepide (Dev) reversed 132 mM Polycose-induced suppression to the level
      of control intake and significantly attenuated 263 mM Polycose-induced
      suppression greater than either antagonist alone. Similar results were observed
      when subthreshold doses of Ond (500 microg/kg) and Dev (5 microg/kg) were co
      administered prior to 263 mM Polycose infusion. Suppression of intake resulting
      from 130 mM Intralipid was reversed to the level of control when Ond and Dev were
      co-administered at both independent effective doses (1 mg/kg each) and
      subthreshold doses (500 microg/kg and 5 microg/kg, respectively). Finally,
      combined administration of the antagonists increased sucrose intakes beyond
      intakes following control or treatment with either antagonist alone when rats
      were infused with saline. These data demonstrate that intestinal carbohydrates
      and lipids inhibit food intake through simultaneous CCK(1) and 5-HT(3) receptor
      activation and that these receptors appear to completely mediate the Intralipid
      induced suppression of intake.

PMID- 17531278
TI  - Ingesta passage and gastric emptying times in loggerhead sea turtles (Caretta
      caretta).
AB  - Ingesta passage times of soft flat foam dishes and gastric emptying time of
      barium-impregnated polyethylene spheres (BIPS) were measured in 22 and 8
      loggerhead sea turtles (Caretta caretta), respectively. Transit time (T(1)) was
      considered as the time between ingestion and first elimination, and retention
      time (T(50)) and total transit time (T(85)) the expulsion time of 50% and 85% of
      the markers, respectively. The experiments were carried out at different times of
      the year and water temperature was recorded. A set of dorso-ventral radiographs
      was taken to locate the BIPS, and the gastrointestinal anatomy of 5 dead turtles
      was studied to help with interpretation of the radiographs. No significant
      correlation was observed between T(1), T(50), T(85) and minimum straight carapace
      length (SCLmin) or body mass and no statistical difference was found in ingesta
      passage transit times between juvenile (n = 6) and sub-adult turtles (n = 16).
      Mean passage times of the dishes (in days) were: T(1) = 9.05, T(50) = 12.00 and
      T(85) = 13.19. Gastric emptying time using BIPS was 24-48 h. The transit time
      (T(1)) for the BIPS was longer (13.25 +/- 4.86 days) than the foam markers (8.5
      +/- 2.73 days) in 8 turtles studied simultaneously. Although the total transit
      time tended to be faster in turtles submitted to water temperatures between 20
      degrees C and 23.6 degrees C no significant correlation was observed between
      T(1), T(50) and T(85) and the temperature.

PMID- 17531279
TI  - Randomized, controlled, double-blind trial with ivermectin on Loa loa
      microfilaraemia: efficacy of a low dose (approximately 25 microg/kg) versus
      current standard dose (150 microg/kg).
AB  - Neurological serious adverse events (SAEs) following ivermectin treatment may
      occur in individuals harbouring high Loa loa microfilarial densities and are of
      major concern in the context of mass ivermectin distributions organized in Africa
      for onchocerciasis and lymphatic filariasis control. As those SAEs are induced by
      the rapid and massive microfilaricidal effect of a standard dose of ivermectin
      (150 microg/kg), we performed a randomized, controlled, double-blind trial to
      determine whether ivermectin given as: (a) a single low dose of 1.5mg (i.e. 25
      microg/kg for a 60 kg person); or (b) two doses of 1.5mg given at a 2 week
      interval leads to a more progressive decrease in Loa microfilarial loads compared
      with the standard dosage. A low dose of ivermectin brought about a significantly
      smaller decrease in Loa microfilaraemia than the standard dose. However, this
      decrease was not sufficiently different from that obtained after the standard
      dose to be acceptable to public health programmes, which require a wide safety
      margin. A second low dose of ivermectin given 15 days after the first dose did
      not lead to a further decrease in Loa microfilaraemia. Lastly, the variability in
      the response observed in the group treated with 25 microg/kg suggests that even
      lower doses would have no effect on a significant number of patients. Ivermectin
      given at a low dose (<or=25 microg/kg) is probably not adequate to prevent the
      occurrence of post-treatment neurological SAEs.

PMID- 17531280
TI  - Fixation probability for a beneficial allele and a mutant strategy in a linear
      game under weak selection in a finite island model.
AB  - The effect of population structure on the probability of fixation of a newly
      introduced mutant under weak selection is studied using a coalescent approach.
      Wright's island model in a framework of a finite number of demes is assumed and
      two selection regimes are considered: a beneficial allele model and a linear game
      among offspring. A first-order approximation of the fixation probability for a
      single mutant with respect to the intensity of selection is deduced. The
      approximation requires the calculation of expected coalescence times, under
      neutrality, for lineages starting from two or three sampled individuals. The
      results are obtained in a general setting without assumptions on the number of
      demes, the deme size or the migration rate, which allows for simultaneous
      coalescence or migration events in the genealogy of the sampled individuals.
      Comparisons are made with limit cases as the deme size or the number of demes
      goes to infinity or the migration rate goes to zero for which a diffusion
      approximation approach is possible. Conditions for selection to favor a mutant
      strategy replacing a resident strategy in the context of a linear game in a
      finite island population are addressed.

PMID- 17531281
TI  - Sperm ultrastructure in Chironomoidea (Insecta, Diptera).
AB  - The fine structure of spermatozoa from several species of chironomids, of
      Culicoides sp. (Ceratopogonidae) and of Odagmia pontina (Simulidae) was studied.
      A synapomorphic feature, consisting of nine kidney-shaped structures forming the
      centriole adjunct, was found in the chironomid species. All members of
      Chironomoidea share a mono-layered acrosome and a flagellar axoneme, provided
      with accessory tubules with 15 protofilaments in their tubular wall. The axoneme
      has a 9+9+2 pattern, but in an unidentified species of chironomid, a 9+9+0 model
      was observed where the central complex and the spokes are missing. Sperm motility
      is, however, maintained in all the examined species. The spermatozoa of this
      taxon have the tendency to complete maturation during their progression along the
      deferent ducts. Thus, in the proximal region of these ducts, they often show
      remnants of the spermatid cytoplasm.

PMID- 17531283
TI  - Modelling of reactivation after UV disinfection: effect of UV-C dose on
      subsequent photoreactivation and dark repair.
AB  - The increased use of UV radiation as a wastewater treatment technology has
      stimulated studies of the repair potential of microorganisms following treatment.
      In this study, samples of unfiltered secondary effluent were irradiated with
      seven levels of UV-C doses (50-200 mW s/cm(2)) from six low-pressure lamps in an
      open-channel UV disinfection system. Following irradiation, samples were
      incubated at 20 degrees C under photoreactivating light or in darkness. Samples
      were analysed for 240 min following incubation. The logistic model is proposed to
      explain the relation between photoreactivation and the UV-C dose received by the
      microorganisms. That model accurately fitted the data obtained in
      photoreactivation experiments, permitting interpretation of the estimated kinetic
      parameters: S(m) and k(2). In the experiments carried out in darkness, a slight
      reactivation is observed (<0.1%), followed by a decay period in which survival
      decreases. In order to model this last period, a modification was made to the
      logistic model by including a term of mortality that assumes a zero-order
      kinetic. The parameters S(m) and k(2), in both photoreactivation and darkness,
      show an exponential dependence on the UV-C inactivating dose. It is possible to
      predict their values, and hence the reactivation curve, from the equations
      proposed in this work.

PMID- 17531284
TI  - Polychlorinated biphenyl, polychlorinated dibenzo-p-dioxin and polychlorinated
      dibenzofuran residues in sediments and fish of the River Nile in the Cairo
      region.
AB  - The levels of organohalogenated contaminants, i.e. PCBs, PCDDs and PCDFs were
      determined in sediment and fish samples collected from different locations in the
      River Nile, Egypt. Thirty-six sediment and eighteen fish samples were carried out
      during a period of 12 months from February 2003 to February 2004. Determination
      of PCBs and dioxins was carried out using a high resolution GC mass spectrometer.
      The results indicated that the PCB and PCDD/F mean concentrations in sediment
      samples ranged from 1461 to 2244 and from 240 to 775pgg(-1) dry wt basis,
      respectively. The mean concentration of PCBs and PCDD/Fs in fish samples were
      found to be in the range from 695 to 853pgg(-1) fresh wt for PCB congeners and
      from 27.7 to 121pgg(-1) lipid for total PCDD/Fs. Moreover, the concentrations of
      both PCBs and PCDD/Fs were found to be different at different locations along the
      River Nile. It could be concluded that the contamination of the River Nile is
      within the permissible limits set by the FDA and the Egyptian Standards for fish
      and shellfish.

PMID- 17531282
TI  - Ubiquitination and proteasomal degradation of interferon regulatory factor-3
      induced by Npro from a cytopathic bovine viral diarrhea virus.
AB  - The pathogenesis of bovine viral diarrhea virus (BVDV) infections is complex and
      only partly understood. It remains controversial whether interferon is produced
      in cells infected with cytopathic(cp) BVDVs which do not persist in vivo. We show
      here that a cpBVDV (NADL strain) does not induce interferon responses in cell
      culture and blocks induction of interferon-stimulated genes by a super-infecting
      paramyxovirus. cpBVDV infection causes a marked loss of interferon regulatory
      factor 3 (IRF-3), a cellular transcription factor that controls interferon
      synthesis. This is attributed to expression of Npro, but not its protease
      activity. Npro interacts with IRF-3, prior to its activation by virus-induced
      phosphorylation, resulting in polyubiquitination and subsequent proteasomal
      degradation of IRF-3. Thermal inactivation of the E1 ubiquitin-activating enzyme
      prevents Npro-induced IRF-3 loss. These data suggest that inhibition of
      interferon production is a shared feature of both ncp and cpBVDVs and provide new
      insights regarding IRF-3 regulation in pestivirus pathogenesis.

PMID- 17531285
TI  - Effects of operating parameters on advanced oxidation of diuron by the Fenton's
      reagent: a statistical design approach.
AB  - Advanced oxidation of diuron in aqueous solution by Fenton's reagent using
      FeSO(4) as source of Fe(II) was investigated in the absence of light. Effects of
      operating parameters namely the concentrations of pesticide (diuron), H(2)O(2)
      and Fe(II) on oxidation of diuron was investigated by using Box-Behnken
      statistical experiment design and the surface response analysis. Diuron oxidation
      by the Fenton reagent was evaluated by determining the total organic carbon
      (TOC), diuron, and adsorbable organic halogen (AOX) removals. Concentration
      ranges of the reagents resulting in the highest level of diuron oxidation were
      determined. Diuron removal increased with increasing H(2)O(2) and Fe(II)
      concentrations up to a certain level. Diuron concentration had a more profound
      effect than H(2)O(2) and Fe(II) in removal of diuron, TOC and AOX from the
      aqueous solution. Nearly complete (98.5%) disappearance of diuron was achieved
      after 15min reaction period. However, only 58% of diuron was mineralized after
      240min under optimal operating conditions indicating formation of some
      intermediate products. Optimal H(2)O(2)/Fe(II)/diuron ratio resulting in the
      maximum diuron removal (98.5%) was found to be 302/38/20 (mgl(-1)).

PMID- 17531287
TI  - Strontium isotopic compositions of dissolved and suspended loads from the main
      channel of the Yangtze River.
AB  - The concentrations of Sr and (87)Sr/(86)Sr isotopic ratios have been measured in
      the dissolved loads from the main channel of the Yangtze River. The result shows
      that the Yangtze River mainstream water has considerably higher Sr concentration
      (202-330 microg kg(-1)) and slightly lower (87)Sr/(86)Sr ratio (0.7098-0.7108)
      than the global average runoff values of dissolved Sr (78 microg kg(-1)) and
      (87)Sr/(86)Sr ratio (0.7119). The (87)Sr/(86)Sr values of 0.7098-0.7108 in river
      waters result from the intense weathering of carbonate and evaporate rocks that
      enriched in the Yangtze River drainage basin. The calculated result based on the
      end-member mixing model shows that about 91% of total dissolved Sr are derived
      from the weathering of carbonate and evaporate rocks and the other 9% derived
      from the weathering of silicate rock. The Yangtze River transports about 1.86 x1
      0(11)g yr(-1) (2.12 x 10(9)mol yr(-1)) of dissolved Sr annually to the East China
      Sea, with an average (87)Sr/(86)Sr of 0.7108. The calculated "(87)Sr(excess)
      flux" of the Yangtze River is about 2.12 x 10(7)mol yr(-1), indicating the
      important impact on seawater Sr isotope evolution. The measured (87)Sr/(86)Sr
      ratios of suspended particulate matters in the Yangtze River water ranging from
      0.7178 to 0.7252, are about 0.015 higher than that of corresponding dissolved
      loads, reflecting more important contribution of silicate particles in suspended
      particulate matters and preferential dissolution of carbonate rocks during basin
      weathering.

PMID- 17531286
TI  - Assessing dimethoate contamination in temperate and tropical climates: potential
      use of biomarkers in bioassays with two chironomid species.
AB  - This study was conducted to investigate the potential use of biomarkers in
      bioassays with chironomids to assess contamination by pesticides in temperate and
      tropical climates. Two species of midge were studied, the widespread Chironomus
      riparius and the tropical Kiefferulus calligaster (Kieffer, 1911). Preliminary
      studies included investigations of the effects of temperature on larval
      development and the influence of larval age on normal variability of
      cholinesterase (ChE) and glutathione S-transferase (GST) activities and protein
      content. In the second phase, the influence of two abiotic factors particularly
      important in tropical conditions (temperature and oxygen concentration) and of
      the organophosphorous (OP) insecticide dimethoate on biochemical and conventional
      endpoints was investigated. Results showed that K. calligaster is morphologically
      and physiologically similar to C. riparius and for both, the time of larval
      development decreases with the increase of temperature. Moreover, 3rd and 4th
      instars appeared to be the most suitable for biomarkers determinations. ChE
      activity seems to be valuable biomarker regarding temperature and dissolved
      oxygen (DO) variations, while some caution should be taken when using GST as an
      environmental biomarker, since it shows some dependence of these parameters. C.
      riparius was more sensitive to dimethoate than K. calligaster suggesting that the
      use of bioassays with the former species in tropical conditions may overestimate
      the toxicity of OP pesticides to autochthonous species. When testing sub-lethal
      effects of dimethoate to C. riparius, ChE activity showed to be a very sensitive
      parameter detecting significant effects at the lowest concentration that caused
      emergence delay of larvae, suggesting that it is an ecologically relevant
      parameter.

PMID- 17531288
TI  - Kinetic and adsorption study of acid dye removal using activated carbon.
AB  - The adsorption of three acid dyes, Acid Red 97, Acid Orange 61 and Acid Brown 425
      onto activated carbon was studied for the removal of acid dyes from aqueous
      solutions at room temperature (25 degrees C). The adsorption of each dye with
      respect to contact time was then measured to provide information about the
      adsorption characteristics of activated carbon. The rates of adsorption were
      found to conform to the pseudo-second-order kinetics with a good correlation. The
      experimental isotherms obtained, except for Acid Orange 61 studied in mixture,
      were of the S-type in terms of the classification of Giles and co-workers. The
      best fit of the adsorption isotherm data was obtained using the Freundlich model.
      When a comparative study was made of the results obtained with single and mixed
      dyes, it can be seen that some of them affect others and modify their behavior in
      the adsorption process. The results indicate that activated carbon could be
      employed for the removal of dyes from wastewater.

PMID- 17531289
TI  - Removal of phosphate from water by a highly selective La(III)-chelex resin.
AB  - A new polymer ligand exchanger (PLE) has been developed for the removal of
      phosphate in wastewater. This PLE, consisting of lanthanum(III) bound to chelex
      100 resin, was prepared by passing LaCl3 solution through a column of chelex-100.
      Uptake of phosphate from water by this La-chelex resin was investigated in the
      column mode. The La-chelex resin was able to remove phosphate efficiently from
      water, and the uptake of phosphate was not affected by the presence of large
      amounts of anions (0.1M) such as chloride and sulfate. The La-chelex resin was
      also able to efficiently remove phosphate from seawater to <0.1mg-Pl(-1), and
      regenerated for reuse by removing the sorbed phosphate by eluting with 6M HCl.

PMID- 17531290
TI  - Emissions of polycyclic aromatic hydrocarbons from thermal pre-treatment of waste
      hydrodesulfurization catalysts.
AB  - Despite increasing environmental concerns and stringent limitations on the sulfur
      content in fuels, many waste hydrodesulfurization (HDS) catalysts containing Co,
      Mo, Ni and V are generated in the petroleum refining process. To recover valuable
      metals in the waste HDS catalysts via hydrometallurgy, thermal treatment is
      usually performed first to remove contaminants (residual oil, carbon and sulfur)
      present on the surface of catalysts. In this study, the mass partitions of
      polycyclic aromatic hydrocarbons (PAHs) in different media (aqueous, particulate
      and gaseous) were quantified in order to determine the efficiency of three
      different air pollution control devices, cooling unit, filter and glass
      cartridge, on PAH removal. An afterburner and two furnace temperatures were used
      to observe the effect on the PAH contents of the treated residues. Results show
      that total-PAH content in treated residues decreased with the pyrolysis
      temperature of the primary furnace, while those generated in flue gases were
      destroyed by the afterburner at an efficiency of approximately 95%. In addition,
      the thermal process converts high molecular weight PAHs to low molecular weight
      PAHs, and the afterburner temperature involved (1200 degrees C) was high enough
      to prohibit the generation of high molecular weight PAHs (HM-PAHs), leading to
      the domination of low molecular weight PAHs (LM-PAHs) in flue gases, while
      treated residues were dominated by HM-PAHs. Finally, information on metal
      contents and their concentrations in the Toxicity Characteristic Leaching
      Procedure in waste HDS catalyst and thermal treated residues are examined as an
      index of the potential for metal recovery.

PMID- 17531291
TI  - Familial genes in sporadic disease: common variants of alpha-synuclein gene
      associate with Parkinson's disease.
AB  - Genetic variation of the alpha-synuclein gene (SNCA) is known to cause familial
      parkinsonism, however the role of SNCA variants in sporadic Parkinson's disease
      (PD) remains elusive. The present study identifies an association of common SNCA
      polymorphisms with disease susceptibility in a series of Irish PD patients. There
      is evidence for association with alternate regions, of protection and risk which
      may act independently/synergistically, within the promoter region (Rep1; OR:
      0.59, 95% CI: 0.37-0.84) and the 3'UTR of the gene (rs356165; OR: 1.67, 95% CI:
      1.08-2.58). Given previous reports of association a collaborative effort is
      required which may exploit global linkage disequilibrium patterns for SNCA and
      standardise polymorphic markers used in each population. It is now crucial to
      identify the susceptibility allele and elucidate its functionality which may
      generate a therapeutic target for PD.

PMID- 17531292
TI  - QSPR modeling of n-octanol/water partition coefficients and water solubility of
      PCDEs by the method of Cl substitution position.
AB  - The number of Cl substitution positions (N(PCS)) of all 209 possible molecular
      structure patterns of polychlorinated diphenyl ethers (PCDEs) were correlated
      with their partition properties n-octanol/water partition coefficient (lgK(ow))
      and sub-cooled liquid water solubilities (-lgS(w,l)). The correlation
      coefficients (R) and the leave-one-out (LOO) cross-validation correlation
      coefficients (R(cv)) of all the 6-descriptor models for lgK(ow) and -lgS(w,l) are
      more than 0.98. By using stepwise multiple regression (SMR), the best two models
      of lgK(ow) with three descriptors (R=0.9,913) and lgS(w,l) with four
      descriptors(R=0.9,818) were obtained respectively. Based on these equations, the
      two properties of all 209 PCDEs were predicted. Model validation showed that the
      two models exhibit optimum stability and high predictive power. Moreover, results
      of prediction were further compared with data from similar studies by molecular
      connectivity indices (MCIs) and PM3 methods.

PMID- 17531293
TI  - FOS expression induced by an ethanol-paired conditioned stimulus.
AB  - To identify brain areas involved in ethanol-induced Pavlovian conditioning,
      brains of male DBA/2J mice were immunohistochemically analyzed for FOS expression
      after exposure to a conditioned stimulus (CS) previously paired with ethanol (2
      g/kg) in two experiments. Mice were trained with a procedure that normally
      produces place preference (Before: ethanol before the CS) or one that normally
      produces place aversion (After: ethanol after the CS). Control groups received
      unpaired ethanol injections in the home cage (Delay) or saline only (Naive). On
      the test day, mice were exposed to the 5-min CS 90 min before sacrifice. Before
      groups showed a conditioned increase in activity, whereas the After group showed
      a conditioned decrease in activity. FOS expression after a drug-free CS exposure
      was significantly higher in Before-group mice than in control mice in the bed
      nucleus of the stria terminalis (Experiment 1) and anterior ventral tegmental
      area (Experiments 1-2). Conditioned FOS responses were also seen in areas of the
      extended amygdala and hippocampus (Experiment 2). However, no conditioned FOS
      changes were seen in any brain area examined in After-group mice. Overall, these
      data suggest an important role for the mesolimbic dopamine pathway, extended
      amygdala and hippocampus in ethanol-induced conditioning.

PMID- 17531294
TI  - Development of eosinophilic conjunctival inflammation at late-phase reaction in
      mast cell-deficient mice.

PMID- 17531295
TI  - Filaggrin null mutations are associated with increased asthma severity in
      children and young adults.
AB  - BACKGROUND: Filaggrin is a key protein involved in skin barrier function.
      Filaggrin (FLG) null mutations are important genetic predisposing factors for
      atopic disease. OBJECTIVE: To study the role of FLG null alleles in the clinical
      phenotype in children and young adults with asthma. METHODS: FLG mutations R501X
      and 2282del4 were assayed in 874 subjects 3 to 22 years old with asthma from
      Tayside. Lung function and disease severity were also studied. RESULTS: The
      filaggrin mutations were significantly associated with greater disease severity
      for asthma. Independent of eczema, mean FEV(1)/forced vital capacity of FLG wild
      type individuals differed from those carrying either FLG null allele (0.89 vs
      0.86; P = .012). Individuals bearing FLG null alleles were more likely to be
      prescribed increased medication (chi(2) = 10.3; P = .001), with the homozygote
      null individuals having an odds ratio of 6.68 (95% CI, 1.7-27.0; P = .008) for
      being prescribed long-acting beta-agonists in addition to inhaled steroids. FLG
      null alleles were also associated with increased rescue medication use (P =
      .004). Individuals with asthma and with FLG null alleles were more likely to have
      eczema, and individuals with eczema tended to have more severe asthma; however,
      the association of FLG null alleles with all markers of asthma disease severity
      was similar in children with and without eczema. CONCLUSION: FLG mutations are
      associated not only with eczema-associated asthma susceptibility but also with
      asthma severity independent of eczema status. CLINICAL IMPLICATIONS: FLG status
      influences controller and reliever medication requirements in children and young
      adults with asthma.

PMID- 17531296
TI  - Improvement of sublingual immunotherapy efficacy with a mucoadhesive allergen
      formulation.
AB  - BACKGROUND: Sublingual immunotherapy is a noninvasive and efficacious treatment
      of type I respiratory allergies. A murine model of sublingual immunotherapy is
      needed to understand better the immune mechanisms involved in successful
      immunotherapy and to assess second-generation candidate vaccines. OBJECTIVE:
      Herein, we developed a therapeutic murine model of sublingual immunotherapy in
      which we document the value of mucoadhesive formulations to enhance treatment
      efficacy. METHODS: BALB/c mice were sublingually treated with soluble or
      formulated ovalbumin before or after sensitization with ovalbumin. Airways
      hyperresponsiveness and lung inflammation were assessed by whole-body
      plethysmography and lung histology, respectively. Humoral and cellular immune
      responses were monitored by ELISA and ELISPOT techniques. RESULTS: Prophylactic
      sublingual administration of ovalbumin completely prevents airways
      hyperresponsiveness as well as IL-5 secretion and IgE induction. Therapeutic
      administration of ovalbumin as a solution via either the sublingual or oral route
      has a limited efficacy. In contrast, sublingual application of ovalbumin
      formulated with maltodextrin to enhance mucosal adhesion results in a major
      reduction of established airways hyperresponsiveness, lung inflammation, and IL-5
      production in splenocytes. This mucoadhesive formulation significantly enhances
      ovalbumin-specific T-cell proliferation in cervical but not mesenteric lymph
      nodes, and IgA production in the lungs. CONCLUSION: A mucoadhesive maltodextrin
      formulation of ovalbumin enhances priming of the local mucosal immune system and
      tolerance induction via the sublingual route. CLINICAL IMPLICATIONS: Mucoadhesive
      formulations offer the opportunity to improve dramatically sublingual
      immunotherapy in human beings, most particularly by simplifying immunization
      schemes.

PMID- 17531297
TI  - Lack of association between indoor allergen sensitization and asthma morbidity in
      inner-city adults.
AB  - BACKGROUND: Sensitivity and exposure to indoor allergens is associated with
      increased asthma morbidity in inner-city children. However, it is unknown whether
      sensitization is associated with worse asthma in adults. OBJECTIVE: To evaluate
      the relationship between sensitization and asthma morbidity in urban adults.
      METHODS: We prospectively studied 245 adults with persistent asthma recruited
      from an inner-city clinic. Sensitization to indoor allergens was evaluated by
      specific IgE antibodies measured at enrollment. Data on asthma control, asthma
      related emergency department visits, hospitalizations, and oral steroid use were
      collected at baseline and at 1-month and 3-month follow-up contacts. Univariate,
      stratified, and multiple regression analyses were used to compare asthma
      morbidity in sensitized and nonsensitized patients after controlling for self
      reported exposure and other potential confounders. RESULTS: The study cohort
      consisted predominantly of low income, minority patients with high rates of
      resource utilization. The prevalences of sensitization to cockroach, dust mite,
      cat, mold, and mouse were 60%, 43%, 41%, 21%, and 14%. On univariate analyses,
      patients sensitized to each allergen did not have worse asthma control or higher
      resource utilization compared with nonsensitized individuals. Stratified and
      multivariate analyses also showed no association between sensitization and
      several measures of asthma morbidity even after controlling for self-reported
      exposure to indoor allergens and other potential confounders. CONCLUSION:
      Sensitization to indoor allergens does not appear to be associated with increased
      asthma morbidity in inner-city adults. CLINICAL IMPLICATIONS: These findings
      suggest that efforts to improve asthma control among urban populations should
      focus on other modifiable risk factors for morbidity.

PMID- 17531298
TI  - IL-10 inhibits CD28 and ICOS costimulations of T cells via src homology 2 domain
      containing protein tyrosine phosphatase 1.
AB  - BACKGROUND: Specific T-cell activation requires T-cell receptor stimulation and
      the generation of costimulatory signals. Major costimulatory signals are
      delivered to T cells by the interaction of CD28 and inducible costimulator
      (ICOS). OBJECTIVE: To investigate the molecular pathways involved in direct T
      cell suppression by IL-10. METHODS: T-cell proliferation analysis,
      immunoprecipitations, and Western blots were performed after T-cell receptor and
      CD28 and ICOS stimulations in the absence or presence of IL-10. Dominant-negative
      src homology 2 domain-containing protein tyrosine phosphatase 1 (SHP-1)
      overexpression, small inhibitory RNA, and SHP-1-deficient and IL-10-deficient
      mice were used. RESULTS: IL-10 receptor-associated tyrosine kinase Tyk-2 acts as
      a constitutive reservoir for SHP-1 in resting T cells, and then tyrosine
      phosphorylates SHP-1 on IL-10 binding. SHP-1 rapidly binds to CD28 and ICOS
      costimulatory receptors and dephosphorylates them within minutes. In consequence,
      the binding of phosphatidylinositol 3-kinase to either costimulatory receptor no
      longer occurs, and downstream signaling is inhibited. Accordingly, spleen cells
      from SHP-1-deficient mice showed increased proliferation with CD28 and ICOS
      stimulation in comparison with wild-type mice, which was not suppressed by IL-10.
      Generation of dominant-negative SHP-1-overexpressing T cells or silencing of the
      SHP-1 gene by small inhibitory RNA both altered SHP-1 functions and abolished the
      T-cell suppressive effect of IL-10. CONCLUSION: The rapid inhibition of the CD28
      or ICOS costimulatory pathways by SHP-1 represents a novel mechanism for direct T
      cell suppression by IL-10. CLINICAL IMPLICATIONS: Molecular mechanisms of direct
      T-cell suppression by IL-10 may provide a novel target for therapy of
      allergy/asthma and autoimmune disease.

PMID- 17531299
TI  - Evaluation of BCG administration as an adjuvant to specific immunotherapy in
      asthmatic children with mite allergy.

PMID- 17531300
TI  - Dust mite ingestion-associated, exercise-induced anaphylaxis.

PMID- 17531301
TI  - Selective impairment of Toll-like receptor 2-mediated proinflammatory cytokine
      production by monocytes from patients with atopic dermatitis.
AB  - BACKGROUND: The skin of patients with atopic dermatitis (AD) exhibits a striking
      susceptibility to infection with gram-positive bacteria and herpes simplex virus
      (HSV), which are known to stimulate Toll-like receptor (TLR) 2. OBJECTIVE: We
      investigated whether TLR2-mediated proinflammatory cytokine production by
      monocytes is selectively impaired in patients with AD and, if so, whether high
      FcvarepsilonRI levels on the monocytes could be related to the impairment.
      METHODS: The 2 subpopulations of monocytes, CD14(dim) proinflammatory and
      CD14(bright) classical monocytes, from patients with AD and healthy control
      subjects were stimulated to produce IL-1beta and TNF-alpha with phorbol 12
      myristate 13-acetate/ionomycin, LPS (TLR4 ligand), or Pam3Cys (TLR2 ligand) for 4
      hours, and simultaneous flow cytometric assessment of surface phenotype and
      intracellular cytokine synthesis was performed. Surface expression of TLR2, TLR4,
      and FcvarepsilonRI on the monocyte subpopulations was also assessed by means of
      flow cytometry. RESULTS: TLR2-mediated IL-1beta and TNF-alpha production by
      either the CD14(dim) or CD14(bright) monocytes was found to be selectively
      impaired in patients with AD. The most remarkable reduction in TLR2-mediated
      proinflammatory cytokine production was observed in CD14(dim) monocytes
      expressing high FcvarepsilonRI levels from patients with AD. This reduction was
      restored by means of downregulation of their FcvarepsilonRI expression after
      preculture in the absence of IgE. CONCLUSION: Monocytes, particularly the
      proinflammatory monocytes, from patients with AD are functionally defective in
      their capacity to produce proinflammatory cytokines on TLR2 stimuli in part
      because of the high levels of their FcvarepsilonRI expression. CLINICAL
      IMPLICATIONS: This selective impairment of monocytes would explain why patients
      with AD are specifically susceptible to cutaneous staphylococcal and
      streptococcal and HSV infections.

PMID- 17531302
TI  - Memory B-cell subsets as a predictive marker of outcome in hypogammaglobulinemia
      during infancy.

PMID- 17531304
TI  - A new criterion by which to discriminate between patients with moderate allergic
      rhinitis and patients with severe allergic rhinitis based on the Allergic
      Rhinitis and its Impact on Asthma severity items.
AB  - BACKGROUND: Allergic Rhinitis and its Impact on Asthma (ARIA) differentiates mild
      from moderate/severe patients on the basis of 4 severity items. The high
      prevalence of moderate/severe patients suggests the need to differentiate between
      them. OBJECTIVES: To identify the categorization that maximizes discrimination
      between moderate and severe allergic rhinitis (AR) by using ARIA guidelines.
      METHODS: Observational, cross-sectional study. Clinical characteristics, nasal
      symptoms (Total Symptom Score 4), and health-related quality of life (HRQL;
      Rhinoconjunctivitis Quality of Life Questionnaire and Short Form 12) were
      assessed. The association of severity items (sleep, daily activities/sport,
      work/school, and troublesome symptoms) with symptoms and HRQL was analyzed using
      linear regression models. ANOVA and effect sizes were used to assess differences
      in symptoms and HRQL among groups defined by the number of affected ARIA items.
      RESULTS: Nontreated patients (N = 141) with moderate/severe AR were studied. All
      severity items showed a similar independent association with symptoms and HRQL
      scores, and there were no interaction effects, indicating that categorization of
      patients into moderate and severe could be based only on the number of items
      affected. Effect sizes were highest between patients with 4 affected ARIA items
      and those with 3, 2, or 1 affected item (effect sizes greater than 0.8 in all
      comparisons using Rhinoconjunctivitis Quality of Life Questionnaire and Short
      Form 12 Physical Composite Summary, and greater than 0.5 using the Total Symptom
      Score 4; P < .001). CONCLUSION: Using ARIA severity items, the criterion that
      best discriminates AR severity is considering moderate those with 1 to 3 affected
      items and severe those with 4. CLINICAL IMPLICATIONS: Discrimination between
      patients with moderate and severe AR should help to obtain homogeneous
      populations for both research and clinical purposes.

PMID- 17531305
TI  - Dipeptidyl peptidase IV deficiency increases susceptibility to angiotensin
      converting enzyme inhibitor-induced peritracheal edema.
AB  - BACKGROUND: Serum dipeptidyl peptidase IV (DPPIV) activity is decreased in some
      individuals with ACE inhibitor-associated angioedema. ACE and DPPIV degrade
      substance P, an edema-forming peptide. The contribution of impaired degradation
      of substance P by DPPIV to the pathogenesis of ACE inhibitor-associated
      angioedema is unknown. OBJECTIVES: We sought to determine whether DPPIV
      deficiency results in increased edema formation during ACE inhibition. We also
      sought to develop an animal model using magnetic resonance imaging to quantify
      ACE inhibitor-induced edema. METHODS: The effect of genetic DPPIV deficiency on
      peritracheal edema was assessed in F344 rats after treatment with saline,
      captopril (2.5 mg/kg), or captopril plus the neurokinin receptor antagonist
      spantide (100 mug/kg) by using serial T2-weighted magnetic resonance imaging.
      RESULTS: Serum dipeptidyl peptidase activity was dramatically decreased in DPPIV
      deficient rats (P < .001). The volume of peritracheal edema was significantly
      greater in captopril-treated DPPIV-deficient rats than in saline-treated DPPIV
      deficient rats (P = .001), saline-treated rats of the normal substrain (P <
      .001), or captopril-treated rats of the normal substrain (P = .001). Cotreatment
      with spantide attenuated peritracheal edema in captopril-treated DPPIV-deficient
      rats (P = .005 vs captopril-treated DPPIV-deficient rats and P = .57 vs saline
      treated DPPIV-deficient rats). CONCLUSIONS: DPPIV deficiency predisposes to
      peritracheal edema formation when ACE is inhibited through a neurokinin receptor
      dependent mechanism. Magnetic resonance imaging is useful for modeling ACE
      inhibitor-associated angioedema in rats. CLINICAL IMPLICATIONS: Genetic or
      environmental factors that decrease DPPIV activity might increase the risk of ACE
      inhibitor-associated angioedema.

PMID- 17531306
TI  - WITHDRAWN: Endoscopic evaluation of resistant rhinosinusitis (before and after
      surgery) is now available on the American Academy of Allergy, Asthma & Immunology
      Web site.
AB  - This article has been withdrawn consistent with Elsevier Policy on Article
      Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). The Publisher
      apologizes for any inconvenience this may cause.

PMID- 17531307
TI  - Genetics and genomics to improve fertility in high producing dairy cows.
AB  - Improving dairy cow fertility by means of genetic selection is likely to become
      increasingly important, since it is now well established that declining fertility
      cannot only be arrested by improved management. Profit margins per kg milk
      produced are decreasing, therefore farmers need to reduce cost and increase herd
      size. This restricts the labor input per cow and the disposable cost of getting a
      cow pregnant, whilst at the same time hormone treatments have become less
      acceptable. This makes it unlikely that additional management interventions will
      maintain fertility at acceptable levels in the near future. Genetic improvement
      seems the obvious solution. Effective selection tools are available in most
      Western countries using traditional breeding value estimation procedures. Also,
      in addition to gene assisted selection using individual genes or QTL, high
      throughput Single Nucleotide Polymorphism (SNP) technology allows genetic
      improvement of fertility based on information from the whole genome (tens of
      thousands SNP per animal), i.e. genomic selection. Simulation studies have shown
      that genomic selection improves the accuracy of selecting juvenile animals
      compared with traditional breeding methods and compared with selection using
      information from a few genes or QTL only. Research in the areas genomics and
      proteomics promise to make genetic selection even more effective. The genomic and
      proteomics technologies combined with the bioinformatics tools that support the
      interpretation of gene functioning and protein expression facilitate an exciting
      starting point for the development of new management strategies and tools for the
      improvement of reproductive performance.

PMID- 17531308
TI  - Complications during gestation in the cow.
AB  - Uterine torsion and vaginal prolapse are accidents of gestation; this paper first
      reviews the predisposition, symptoms, diagnosis, and treatment of uterine
      torsion, and the predisposition, pathogenesis, symptoms, treatment, and prognosis
      of vaginal prolapse during late gestation in the cow. Other noninfectious
      complications of gestation are either fetal or placental in origin. Two
      relatively unusual fetal problems, mummification and maceration, are also
      discussed, followed by a comparison of two hydropic conditions (hydrallantois and
      hydramnios). Hydrops allantois, primarily a placental problem, occurs about nine
      times more frequently than hydrops amnii, which is a result of fetal anomalies.
      Abnormal offspring syndrome is a more recent phenomenon associated with the
      transfer of IVF or SCNT embryos. Finally, reference is made to teratology in
      general and a website of illustrations is cited.

PMID- 17531309
TI  - Functional specificity of the visual word form area: general activation for words
      and symbols but specific network activation for words.
AB  - The functional specificity of the brain region known as the Visual Word Form Area
      (VWFA) was examined using fMRI. We explored whether this area serves a general
      role in processing symbolic stimuli, rather than being selective for the
      processing of words. Brain activity was measured during a visual 1-back task to
      English words, meaningful symbols (e.g., $, %), digits, words in an unfamiliar
      language (Hebrew), and geometric control stimuli. Mean activity in the
      functionally defined VWFA, as well as a pattern of whole-brain activity
      identified using a multivariate technique, did not differ for words and symbols,
      but was distinguished from that seen with other stimuli. However, functional
      connectivity analysis of this region identified a network of regions that was
      specific to words, including the left hippocampus, left lateral temporal, and
      left prefrontal cortex. Results support the hypothesis that activity in the VWFA
      plays a general role in processing abstract stimuli; however, the left VWFA is
      part of a unique network of brain regions active only during the word condition.
      These findings suggest that it is the neural "context" of the VWFA, i.e., the
      broader activity distributed in the brain that is correlated with VWFA, that is
      specific for visual word representation, not activity in this brain region per
      se.

PMID- 17531310
TI  - Severity of dysfluency correlates with basal ganglia activity in persistent
      developmental stuttering.
AB  - Previous studies suggest that anatomical anomalies [Foundas, A. L., Bollich, A.
      M., Corey, D. M., Hurley, M., & Heilman, K. M. (2001). Anomalous anatomy of
      speech-language areas in adults with persistent developmental stuttering.
      Neurology, 57, 207-215; Foundas, A. L., Corey, D. M., Angeles, V., Bollich, A.
      M., Crabtree-Hartman, E., & Heilman, K. M. (2003). Atypical cerebral laterality
      in adults with persistent developmental stuttering. Neurology, 61, 1378-1385;
      Foundas, A. L., Bollich, A. M., Feldman, J., Corey, D. M., Hurley, M., & Lemen,
      L. C. et al., (2004). Aberrant auditory processing and atypical planum temporale
      in developmental stuttering. Neurology, 63, 1640-1646; Jancke, L., Hanggi, J., &
      Steinmetz, H. (2004). Morphological brain differences between adult stutterers
      and non-stutterers. BMC Neurology, 4, 23], in particular a reduction of the white
      matter anisotropy underlying the left sensorimotor cortex [Sommer, M., Koch, M.
      A., Paulus, W., Weiller, C., & Buchel, C. (2002). Disconnection of speech
      relevant brain areas in persistent developmental stuttering. Lancet, 360, 380
      383] could be at the origin of persistent developmental stuttering (PDS). Because
      neural connections between the motor cortex and basal ganglia are implicated in
      speech motor functions, PDS could also be associated with a dysfunction in basal
      ganglia activity [Alm, P. (2004). Stuttering and the basal ganglia circuits: a
      critical review of possible relations. Journal of Communication Disorders, 37,
      325-369]. This fMRI study reports a correlation between severity of stuttering
      and activity in the basal ganglia and shows that this activity is modified by
      fluency shaping therapy through long-term therapy effects that reflect speech
      production improvement. A model of dysfunction in stuttering and possible repair
      modes is proposed that accommodates the data presented here and observations
      previously made by us and by others.

PMID- 17531311
TI  - Polymerization shrinkage of experimental short glass fiber-reinforced composite
      with semi-inter penetrating polymer network matrix.
AB  - OBJECTIVES: The aim of this study was to determine the magnitude of short fiber
      reinforced composite resin, with a semi-IPN-polymer matrix, on polymerization
      resin shrinkage-strain, shrinkage stress and marginal microleakage of the
      restoration. MATERIALS AND METHODS: Experimental composite FC resin was prepared
      by mixing 22.5 wt.% of short E-glass fibers, 22.5 wt.% of IPN-resin and 55 wt.%
      of silane treated silica fillers using a high speed mixing machine. As control
      material, commercial particulate filler composite resin (PFC) was used.
      Polymerization shrinkage-strain and stress of the specimens (n=5) were measured
      using the bonded-disc technique and tensilometer, respectively with respect to
      time. FC composite and PFC were placed incrementally in class II cavities sized 4
      mm x 4 mm x 6 mm (n=8/group) using total-etch adhesive system according to
      manufacturer's instructions. After the class II restorations were completed, the
      specimens were finished and polished, thermocycled, stained, sectioned, and
      viewed under a stereo-microscope for leakage at occlusal/enamel and
      gingival/dentin margins. The data were analyzed using ANOVA. RESULTS: ANOVA
      revealed that restorations made from experimental FC composite had a
      significantly lower shrinkage stress and microleakage than those made from PFC
      (p<0.05). The data show that gingival margins had higher microleakage than that
      obtained from occlusal margins of restorations (p<0.05). CONCLUSIONS: The use of
      short fiber filler with semi-IPN polymer matrix reduced polymerization shrinkage
      stress and microleakage compared to a conventional restorative composite.

PMID- 17531312
TI  - Influence of chain extender length of aromatic dimethacrylates on polymer network
      development.
AB  - OBJECTIVE: To investigate the role of chain extender size from Bis-EMA monomers
      on the polymerization profiles and properties of the crosslinked polymers.
      Additionally, the influence of Bis-GMA was also evaluated. METHODS: The polymer
      network from homopolymers Bis-EMA4, Bis-EMA10 and Bis-EMA30 was characterized, as
      well as copolymers formed among these monomers and Bis-GMA. The degree of
      conversion from neat and blended monomers as a function of photo-activation time
      was evaluated by FTIR. Rate of polymerization, network parameter and cross-link
      density from materials were demonstrated. Water sorption and solubility were
      determined according to ISO 4049 specification and the data obtained were
      analyzed by two-way ANOVA/Tukey's test (alpha=0.05). Flexural strength and
      Young's modulus from polymerized monomers/co-monomers were measured after 24h
      water storage at 37 degrees C and the results were analyzed by one-way
      ANOVA/Tukey's test (alpha=0.05). RESULTS: Monomers with larger ethylene oxide
      units presented the highest values regarding the degree of conversion and cross
      link density. The effect of the chain extender length was also observed in water
      sorption and solubility polymer characteristics, with Bis-EMA4 being the most
      hydrophobic polymer. Bis-EMA10 and Bis-EMA30 homopolymers were not able to be
      tested with the three point bending test due to their great flexibility. The
      addition of Bis-GMA produced stronger and more rigid Bis-EMA polymers (p<0.05).
      SIGNIFICANCE: Aromatic dimethacrylates with different chain extender lengths can
      be a useful alternative in controlling the properties of a dental material,
      adjusting those to specific applications.

PMID- 17531313
TI  - Purification of guar gum for biological applications.
AB  - Commercial guar gum (GG) was purified by four different methods and characterized
      by gel permeation chromatography (GPC), thermogravimetric analysis and the
      determination of monosaccharides composition, protein and copper content,
      turbidity, intrinsic viscosity and rheological parameters. The first method was
      based on enzymatic hydrolysis with porcine pancreatin. In the second method
      successive gum dissolution, centrifugation and precipitation with acetone and
      ethanol were carried out. Precipitation with Fehling solution was employed in the
      third method. In the fourth method, the gum was purified by method 2 and then by
      method 3. All methods led to a reduction in protein content, arabinose and
      glucose residues, considered as sugar contaminants, and also in intrinsic
      viscosity and molar mass. Total elimination of protein was only achieved by
      method 4. Using methods 3 and 4, the gum was contaminated with small amounts of
      Cu(II) from the Fehling solution. Methods 2 and 4 apparently provided purer guar
      gum. If the amount of protein is a crucial parameter in the biological
      application and the guar will be taken in low amounts, method 4 is recommended.
      Taking into account the purity, thermal stability, rheological parameters of the
      purified gum and also the cost and simplicity of the procedure, method 2 has
      wider biological application.

PMID- 17531314
TI  - Inhibitory kinetics of bromacetic acid on beta-N-acetyl-D-glucosaminidase from
      prawn (Penaeus vannamei).
AB  - beta-N-Acetyl-D-glucosaminidase (NAGase, EC.3.2.1.52), a composition of
      chitinases, cooperates with endo-chitinase and exo-chitinase to disintegrate
      chitin into N-acetylglucosamine (NAG). NAGase from prawn (Penaeus vannamei) is
      involved in digestion and molting processes. The investigation of enzymatic
      properties, functional groups and catalytic mechanism is an essential mission to
      its commercial application. Bromacetic acid (BrAc) is a specific modifier for the
      histidine residue in specific condition. In this paper, the effect of BrAc on
      prawn NAGase activity for the hydrolysis of pNP-NAG has been investigated. The
      results showed that BrAc can reversibly and non-competitively inhibit the enzyme
      activity at appropriate concentrations and the value of IC(50) was estimated to
      be 17.05+/-0.65 mM. The inhibition kinetics of the enzyme by BrAc has been
      studied using the kinetic method of the substrate reaction. And the inhibition
      model was set up and the microscopic rate constants for the reaction of the
      inhibitor with free enzyme and the enzyme-substrate complexes were determined for
      inactivation and reactivation. The rate constant of the forward inactivation
      (k(+0)), which is 1.25 x 10(-3)s(-1), is about eight times as much as that of the
      reverse reactivation (k(-0)), which is 1.64 x 10(-4)s(-1). Therefore, when the
      BrAc concentration is sufficiently large, the enzyme is completely inactivated.

PMID- 17531315
TI  - Placental expression of EG-VEGF and its receptors PKR1 (prokineticin receptor-1)
      and PKR2 throughout mouse gestation.
AB  - Compelling evidence indicates that vascular endothelial growth factor (VEGF) is
      an important mediator of placental angiogenesis and appears to be disregulated in
      pre-eclampsia (PE). Recently, we characterised the expression of EG-VEGF
      (endocrine gland-derived vascular endothelial growth factor), also known as
      prokineticin 1 (PK1) in human placenta during the first trimester of pregnancy
      and showed that this factor is likely to play an important role in human
      placentation. However, because it is impossible to prospectively study
      placentation in humans, it has been impossible to further characterise EG-VEGF
      expression throughout complete gestation and especially at critical gestational
      ages for PE development. In the present study, we used mouse placenta to further
      characterise EG-VEGF expression throughout gestation. We investigated the pattern
      of expression of EG-VEGF and its receptors, PKR1 and PKR2 at the mRNA and protein
      levels. Our results show that EG-VEGF and VEGF exhibit different patterns of
      expression and different localisations in the mouse placenta. EG-VEGF was mainly
      localised in the labyrinth whereas VEGF was mainly present in glycogen and giant
      cells. EG-VEGF mRNA and protein levels were highest before 10.5days post coitus
      (dpc) whereas those of VEGF showed stable expression throughout gestation. PKR1
      protein was localised to the labyrinth layer and showed the same pattern of
      expression as EG-VEGF whereas PKR2 expression was maintained over 10.5dpc with
      both trophoblastic and endothelial cell localisations. Altogether these findings
      suggest that EG-VEGF may have a direct effect on both endothelial and
      trophoblastic cells and is likely to play an important role in mouse
      placentation.

PMID- 17531316
TI  - Expression of TGF beta in the placental bed is not altered in sporadic
      miscarriage.
AB  - Extravillous trophoblast invasion of uterine stroma and spiral arteries (SA) is
      essential for normal pregnancy and is reduced in preeclampsia and late
      miscarriage. The control mechanisms are not understood, but transforming growth
      factor-beta (TGF-beta) may be a candidate. Placental and placental bed biopsies
      were obtained from early (8(+0)-12(+6) weeks) euploid miscarriages (n = 10),
      early aneuploid miscarriages (n = 10), late (13(+0)-19(+6) weeks) euploid
      miscarriages (n = 10) and controls of the same gestation (n = 20). Frozen
      sections were immunostained for TGF-beta1, 2 and 3. Immunoreactivity of
      trophoblast and uterine cell populations was assessed semi-quantitatively. TGF
      beta1 immunolocalization was limited to extracellular matrix in cytotrophoblast
      islands and cytotrophoblast shell, perivascular fibrinoid and interstitial
      trophoblast and did not differ in miscarriage compared with controls. TGF-beta2
      was expressed additionally in endovascular trophoblast and multinucleate
      trophoblast giant cells. There was no aberrant TGF-beta2 immunolocalization in
      late miscarriage, but TGF-beta2 immunoreactivity was increased in extracellular
      matrix in cytotrophoblast islands in early miscarriage. TGF-beta3 was absent from
      all cell populations. Stromal and extravillous trophoblast TGF-beta2
      immunolocalization suggests a more important role in trophoblast invasion than
      TGF-beta1, but neither isoform was altered in miscarriage. Altered TGF-beta
      localization is therefore unlikely to play a role in abnormal trophoblast
      invasion and SA transformation in miscarriage.

PMID- 17531317
TI  - Biodegradation of microcystins by aquatic Burkholderia sp. from a South Brazilian
      coastal lagoon.
AB  - Biological degradation of cyanobacterial hepatotoxin microcystins in estuarine
      and coastal water samples from the Patos Lagoon estuarine system, a coastal
      lagoon situated at the southernmost region of Brazil, was observed. Samples of
      natural surface water were spiked with purified and semi-purified microcystins
      (MC-LR and [D-Leu(1)]MC-LR) and their concentrations were monitored by HPLC
      analysis. After 15 days, the toxins were no longer detectable and after 43 days
      less than 90% of the initial concentration added to the samples was detected by
      ELISA. The average degradation rates and the exponential decay rate constants
      from inside and outside of the estuary were similar. A microcystin degradative
      bacterium was isolated from the estuarine region. Partial sequence of the 16S
      rDNA showed a 96% homology with the Burkholderia genus. This genus belongs to the
      beta subdivision on proteobacteria. This is the first report showing the genus
      Burkholderia as a cyanobacterial toxin degrader.

PMID- 17531318
TI  - Multiple-locus variable-number tandem repeat analysis (MLVA) of Leptospira
      interrogans serovar Pomona from Argentina reveals four new genotypes.
AB  - Outbreaks of leptospirosis occur regularly in Argentina, but little is known
      about their epidemiological relationships. We have analyzed the genetic diversity
      of a collection of 16 strains of Leptospira interrogans serovar Pomona isolated
      from animals and humans in Argentina during the past 45 years. Genotyping was
      performed by multiple-locus variable-number tandem repeat analysis (MLVA) using
      the loci VNTR4, VNTR7, VNTR9, VNTR10, VNTR19, VNTR23 and VNTR31, as described by
      Majed et al. [Identification of variable-number tandem-repeat loci in Leptospira
      interrogans sensu stricto. J Clin Microbiol 2005;43:539-45]. Clustering analysis
      revealed four new distinct MLVA genotypes, with a dominant one. Strains with this
      genotype were consistently isolated since 1960 to the present, mainly from cows
      and pigs, but also from humans, representing 75% of the total strains studied.
      These strains coexisted temporally and geographically with isolates presenting
      the other new genotypes. VNTR4 locus, with four different alleles, presented the
      highest diversity between the VNTR loci analyzed. MLVA patterns obtained will be
      useful for future diagnostic and epidemiological tracing analysis.

PMID- 17531319
TI  - Molecular and functional characterization of a CD59 analogue from large yellow
      croaker Pseudosciana crocea.
AB  - CD59 is a widely distributed membrane-bound inhibitor of the cytolytic membrane
      attack complex (MAC) of complement. Here, the cDNA of a CD59 analogue was cloned
      from large yellow croaker (Pseudosciana crocea), a marine fish (LycCD59), by
      expressed sequence tags (EST) and RACE techniques. The open reading frame (ORF)
      of 351 nucleotides (nt) of LycCD59 encodes a polypeptide of 117 amino acids (aa),
      which includes a putative 20-aa NH(2)-signal peptide and a 97-aa coding region
      with a putative GPI-anchoring site at Asn(71). The deduced LycCD59 protein shared
      the structural feature of mammalian CD59, including a conserved cysteine skeleton
      responsible for the formation of disulfide bonds, and a similar pattern of
      hydrophobic termini. RT-PCR analysis showed that LycCD59 mRNA was broadly
      expressed in various tissues examined, except for intestine. And Northern blot
      analysis revealed a single LycCD59 transcript of approximately 1.0kb. LycCD59
      expression in blood, spleen, and kidney was significantly up-regulated during 24h
      of induction with poly(I:C) or inactivated trivalent bacterial vaccine as
      determined by a relative quantitative real-time PCR analysis, and a coordinated
      up-regulation of LycCD59 and complement C3 and C7 mRNA was also found in these
      three tissues post-induction although their up-regulation pattern and extent were
      somewhat different in various tissues with poly(I:C) or bacterial vaccine. The
      recombinant protein of LycCD59 produced in E. coli was shown to significantly
      inhibit the erythrocyte lysis of tilapia (Oreochromis niloticus) in an in vitro
      hemolytic system, which was mediated by serum from large yellow croaker and
      tilapia, respectively, but not from mouse and chicken, suggesting that LycCD59
      has a species-selective inhibition of complement activation. These results
      represent the first functional identification of a CD59 analogue in teleost fish,
      strongly suggesting the presence of regulatory mechanism for terminal complement
      pathway in teleost fish.

PMID- 17531320
TI  - Merkel cell carcinoma of the eyelid review of the literature and report of
      patients with Merkel cell carcinoma showing spontaneous regression.
AB  - PURPOSE: To evaluate the clinical and histopathologic characteristics of Merkel
      cell carcinoma (MCC) of the eyelid. DESIGN: Retrospective case series and
      literature review. PARTICIPANTS: Three consecutive patients with MCC of the
      eyelid who were referred to the Ocular Oncology Unit of Leiden University Medical
      Center, Netherlands. METHODS: Clinical records and histopathologic material of
      patients with eyelid MCC were reviewed. The clinical presentation and treatment
      were evaluated. MAIN OUTCOME MEASURES: Clinical and histopathologic description
      of eyelid MCC, with histologic proof of spontaneous regression of the tumor.
      RESULTS: Three patients with MCC of the eyelid were included. Diagnosis was made
      by pathologic investigation and immunohistochemistry (S100, cytokeratin 20,
      epithelial membrane antigen, chromogranin). Two of the patients showed
      histologically proven complete spontaneous regression after nonradical excision
      of the tumor. After local excision, none of the MCCs demonstrated local
      recurrence, without regional or distant metastases. Mean clinical follow-up was
      50 months. CONCLUSIONS: Nonocular MCC is known to recur in 66% of patients and to
      be lethal in almost 33%. Merkel cell carcinoma of the eyelid is a rare malignancy
      that can not be recognized clinically. Clinical differential diagnosis must be
      made with a chalazion, and histopathologic differential diagnosis must be made
      with small cell carcinomas. Close follow-up of these patients is advised because
      of the potential high recurrence rate and lymphatic spread. The immunologic
      phenomenon of spontaneous regression points out the importance of the immune
      system in this disease.

PMID- 17531321
TI  - 1H and 13C NMR study of the complex formed by copper(II) with the nucleoside
      antibiotic sinefungin.
AB  - Sinefungin (SFG) is an antifungal and antiparasitic nucleoside antibiotic
      composed by ornithine and adenosine moieties both having the potential to bind
      copper(II). NMR studies performed at physiological pH have shown that the alpha
      amino and the carboxylate groups in the ornithine unit are the preferred donor
      sites for Cu(II) binding. On the contrary, at acidic pH, Cu(II) complexation
      starts from adenosine nitrogen being the alpha-amino group still protonated and
      not available for metal binding. The proton paramagnetic relaxation enhancements
      measured at neutral pH allowed to obtain the 3D structure of the 1:2 Cu(II)-SFG
      complex. Molecular dynamics calculations were revealing for the existence of
      secondary Cu(II) interaction with the purine nitrogens of the adenosine moiety.

PMID- 17531322
TI  - Effects of inorganic selenium compounds on oxidative DNA damage.
AB  - Exposure of Escherichia coli or mammalian cells to H2O2 results in cell death due
      to iron-mediated DNA damage. Since selenium compounds have been examined for
      their ability to act as antioxidants to neutralize radical species, and inorganic
      selenium compounds are used to supplement protein mixes, infant formula, and
      animal feed, determining the effect of these compounds on DNA damage under
      conditions of oxidative stress is crucial. In the presence of Fe(II) and H2O2,
      the effects of Na2SeO4, Na2SeO3, SeO2 (0.5-5000 microM), and Na2Se (0.5-200
      microM) on DNA damage were quantified using gel electrophoresis. Both Na2SeO4 and
      Na2Se have no effect on DNA damage, whereas SeO2 inhibits DNA damage and Na2SeO3
      shows antioxidant or pro-oxidant activity depending on H2O2 concentration.
      Similar electrophoresis experiments with [Fe(EDTA)](2-) (400 microM) and Na2SeO3
      or SeO2 show that metal coordination by the selenium compound is required for
      antioxidant activity. In light of these results, Na2SeO4 may be safer than
      Na2SeO3 for nutritional supplements.

PMID- 17531323
TI  - What's new on CDC25 phosphatase inhibitors.
AB  - The CDC25 phosphatases are key regulators of cell cycle progression and play a
      central role in the checkpoint response to DNA damage. Their inhibition may
      therefore represent a promising therapeutic approach in oncology, and small
      molecule design strategies are currently leading to the identification of various
      classes of CDC25 inhibitors. Most structures developed so far are quinonoid-based
      compounds, but also phosphate surrogates or electrophilic entities. Considering
      the characteristics of the highly conserved active sites of the enzymes, many
      mechanisms of action have been proposed for these inhibitors. Quinonoid compounds
      may oxidize the catalytic site cysteine, but can also be considered as Michael
      acceptors capable of reacting with the activated thiolate or other electrophilic
      entities. Phosphate surrogates are thought to interfere with the arginine
      residue, leading to reversible enzyme inhibition. But some inhibitors can combine
      in the same molecule several of these mechanisms, thus by fitting into the active
      site of the enzyme through one part of the molecule and bringing the reactive
      moiety in close proximity to the catalytic cysteine. This review summarizes novel
      classes of inhibitors that show specificity for the CDC25s over other
      phosphatases, cause cell proliferation inhibition and cell cycle arrest in vitro
      but also, for several of them, inhibition of xenografted tumoral cell growth in
      vivo. These promising results confirm the interest of the inhibition of CDC25
      phosphatases as an anticancer therapeutic strategy.

PMID- 17531324
TI  - Recent developments in the significance and therapeutic relevance of neuroactive
      steroids--Introduction to the special issue.
AB  - This special issue heralds an exciting time in the field when the significance of
      neuroactive steroids in the regulation of inhibitory transmission is being
      realized and translated to new treatments for intractable neurologic and
      psychiatric conditions. In the past year, the binding sites for neuroactive
      steroids on gamma-aminobutyric acid type A (GABA(A)) receptors have been
      discovered and clinical trials for epilepsy and traumatic brain injury have been
      successful. New data in animal models points to the potential value of
      neuroactive steroids in other central nervous system (CNS) disorders including
      depression, schizophrenia, alcoholism, multiple sclerosis and other
      neurodegenerative conditions. How can one class of compounds have so many
      potential applications? The answer may lie in the ability of neuroactive steroids
      to regulate synaptic and extrasynaptic inhibitory transmission across brain,
      hypothalamic-pituitary-adrenal (HPA) axis function, inflammatory processes and
      myelin formation. The manuscripts in this issue of Pharmacology and Therapeutics
      will bring you up to date on the sites of neurosteroid actions, the systemic and
      molecular consequences of these actions and the potential therapeutic relevance
      of neuroactive steroid effects for CNS disease. These studies point to the
      opportunity for more translational research into potential therapeutic
      applications and the need for evaluation of potential untoward side effects
      following long-term treatment.

PMID- 17531325
TI  - Neurosteroid modulation of synaptic and extrasynaptic GABA(A) receptors.
AB  - Certain naturally occurring pregnane steroids act in a nongenomic manner to
      potently and selectively enhance the interaction of the inhibitory
      neurotransmitter GABA with the GABA(A) receptor. Consequently such steroids
      exhibit anxiolytic, anticonvulsant, analgesic, sedative, hypnotic, and anesthetic
      properties. In both physiological and pathophysiological scenarios, the pregnane
      steroids may function as endocrine messengers (e.g., produced in the periphery
      and cross the blood-brain barrier) to influence behaviour. However, additionally
      "neurosteroids" can be synthesised in the brain and spinal cord to act in a
      paracrine or autocrine manner and thereby locally influence neuronal activity.
      Given the ubiquitous expression of the GABA(A) receptor throughout the mammalian
      central nervous system (CNS), physiological, pathophysiological, or drug-induced
      pertubations of neurosteroid levels may be expected to produce widespread changes
      in brain excitability. However, the neurosteroid/GABA(A) receptor interaction is
      brain region and indeed neuron specific. The molecular basis of this specificity
      will be reviewed here, including (1) the importance of the subunit composition of
      the GABA(A) receptor; (2) how protein phosphorylation may dynamically influence
      the sensitivity of GABA(A) receptors to neurosteroids; (3) the impact of local
      steroid metabolism; and (4) the emergence of extrasynaptic GABA(A) receptors as a
      neurosteroid target.

PMID- 17531326
TI  - Simulation of sleep spindles and spike and wave discharges using a novel method
      for the calculation of field potentials in rats.
AB  - We suggest a new method for calculation of extracellular field potentials
      generated by a large population of pyramidal cells (PCs), using a single PC
      compartmental model. Similar methods described earlier use the assumption that
      the intracellular potential or current distributions of the cells within the
      population are much alike as a result of simultaneous activation at about the
      same longitudinal location (i.e., all the PCs in the population are located on
      the same level and are ideally synchronized). However, the degree of
      synchronization of natural firing even during synchronized rhythmic discharges in
      the cortex is not as high. We introduce the possibility to vary the degree of
      synchronization of the PCs' activity in the population, thus taking into account
      disperse timing of cortical pyramidal cells' firing. The temporal variability in
      cell firing is described by a Gaussian distribution, the width of which defines
      the degree of synchronization/desynchronization. In addition, the suggested
      method allows for certain spatial spread of PCs in the population along
      longitudinal axis of the PCs. The method was applied to test the assumption that
      the transition from sleep spindles to rhythmic spike and wave discharges (SWDs)
      observed in absence epilepsy may occur due to an increase in pyramidal cells'
      firing synchronization. We show that in case of weak synchronization of PC firing
      in the population, the shape of field potential during rhythmic thalamic input is
      similar to the oscillations during a sleep spindle, while at stronger
      synchronization of PCs, it looks much more as a SWD, with clear expressed spikes
      and waves. This suggests that in large population of pyramidal cells the changes
      in the degree of synchronization of cell firing may explain the changes in the
      shape of field potential from spindle oscillations to SWDs and vice versa.

PMID- 17531327
TI  - Olanzapine versus lithium in the acute treatment of bipolar mania: a double
      blind, randomized, controlled trial.
AB  - BACKGROUND: This multicenter, double-blind, randomized, controlled study
      conducted in China examined the efficacy and safety of olanzapine versus lithium
      in the treatment of patients with bipolar manic/mixed episodes. METHODS: Patients
      with bipolar manic or mixed episode (DSM-IV criteria) and Young Mania Rating
      Scale (YMRS) score> or =20 at screening received olanzapine (5-20 mg/day, n=69)
      or lithium carbonate (600-1800 mg/day, n=71) for 4 weeks. The primary outcome was
      mean change from baseline in Clinical Global Impressions-Bipolar Version Overall
      Severity of Illness (CGI-BP) score. Secondary efficacy measures included YMRS,
      Brief Psychiatric Rating Scale (BPRS), and Montgomery-Asberg Depression Rating
      Scale (MADRS) scores. Safety was also assessed. RESULTS: A significantly greater
      mean change was observed in olanzapine versus lithium patients in CGI-BP (Overall
      Severity) (P=0.009), YMRS (P=0.013), BPRS (P=0.032), and CGI-BP (Severity of
      Mania) (P=0.012) scores. More olanzapine than lithium patients experienced at
      least one adverse event possibly related to study drug (P=0.038). More olanzapine
      patients had a clinically significant weight increase (> or =7% of baseline
      weight) compared to lithium patients (P=0.009). More olanzapine patients
      completed the study than lithium patients, although this difference was not
      statistically significant (olz, 91.3%; lith, 78.9%; P=0.057). LIMITATIONS: No
      placebo arm was included; however both treatments have previously been reported
      to be more effective than placebo. CONCLUSIONS: These results suggest that
      olanzapine has superior efficacy to lithium in the acute treatment of patients
      with bipolar mania over a 4-week period. However, adverse events were experienced
      by a greater number of olanzapine patients than lithium patients.

PMID- 17531328
TI  - Pediatric auricular chondrocytes gene expression analysis in monolayer culture
      and engineered elastic cartilage.
AB  - OBJECTIVES: This study was aimed at regenerating autologous elastic cartilage for
      future use in pediatric ear reconstruction surgery. Specific attentions were to
      characterize pediatric auricular chondrocyte growth in a combination culture
      medium and to assess the possibility of elastic cartilage regeneration using
      human fibrin. STUDY DESIGN: Laboratory experiment using human pediatric auricular
      chondrocytes. METHODS: Pediatric auricular chondrocytes growth kinetics and
      quantitative gene expression profile in three different types of media were
      compared in primary culture and subsequent three passages. Large-scale culture
      expanded chondrocytes from the combination medium were then mixed with human
      fibrin for the formation of elastic cartilage via tissue engineering technique.
      RESULTS: The equal mixture of Ham's F12 and Dulbecco's Modified Eagle Medium (FD)
      promoted the best chondrocyte growth at every passage compared to the individual
      media. Chondrocytes differentiation index; ratio of type II to type I collagen
      gene expression level, aggrecan and elastin expression gradually decreased while
      passaging but they were then restored in engineered tissues after implantation.
      The engineered cartilage was glistening white in color and firm in consistency.
      Histological evaluation, immunohistochemistry analysis and quantitative gene
      expression assessment demonstrated that the engineered cartilage resemble the
      features of native elastic cartilage. CONCLUSION: Pediatric auricular
      chondrocytes proliferate better in the combination medium (FD) and the
      utilization of human fibrin as a biomaterial hold promises for the regeneration
      of an autologous elastic cartilage for future application in ear reconstructive
      surgery.

PMID- 17531329
TI  - Motor effects of delta 9 THC in cerebellar Lurcher mutant mice.
AB  - The present study evaluated the effects of the principal active component of
      marijuana (delta 9 THC) on motor abilities and motor learning in mice with
      cerebellar dysfunction. For this purpose, spontaneous locomotor activity,
      equilibrium abilities, muscular tone, motor coordination and motor learning were
      investigated in Lurcher mutant and non-mutant B6/CBA mice 20 min after i.p.
      administration of 4 or 8 mg kg(-1) of delta 9 tetra hydro cannabinol (delta 9
      THC). The performances were compared to those obtained by Lurcher and non-mutant
      mice injected with vehicle (Tween 80). The results showed that at the dose of 4
      mg kg(-1) but not at the dose of 8 mg kg(-1), the cannabinoid (CB) substance
      reduced deficits in motor coordination, equilibrium and muscular tone and
      facilitated motor learning in Lurcher mice. On the other hand, only a muscular
      strength decrease was observed in control B6/CBA mice injected with the dose of 8
      mg kg(-1) of delta 9 THC. These results suggested that cannabinoid derivative
      could represent a new field of investigation concerning the treatment of
      cerebellar ataxic syndrome in humans.

PMID- 17531330
TI  - Altered role of C-type natriuretic peptide-activated pGC-cGMP-PDE3-cAMP signaling
      in hyperthyroid beating rabbit atria.
AB  - The role of C-type natriuretic peptide (CNP) in the pathophysiology of atrial
      function in hyperthyroidism has not been defined. This study was to define the
      role of CNP-activated particulate (p) guanylyl cyclase (GC)-cGMP
      phosphodiesterase (PDE)3 signaling in the regulation of cAMP levels and
      contractile and secretory functions in the atria from hyperthyroid rabbits.
      Experiments were performed in perfused beating rabbit atria. CNP was used to
      activate pGC. In euthyroid atria from sham-treated rabbits, CNP (100 nM)
      increased cGMP and cAMP efflux by 176.7+/-17.7 and 55.3+/-10.0%, respectively.
      CNP decreased stroke volume and pulse pressure and ANP release by 51+/-7 and 41+/
      2 and 60.4+/-3.2%, respectively. Pretreatment with milrinone blocked the CNP
      induced increase of cAMP but without significant changes in decrease of atrial
      dynamics and ANP release. In hyperthyroid atria, CNP-induced increase of cGMP
      levels was accentuated, while CNP-induced increase of cAMP was attenuated. The
      gain of cAMP, i.e., change in cAMP efflux concentration in terms of cGMP was
      attenuated in the hyperthyroid compared to euthyroid atria. CNP rather increased
      atrial dynamics in hyperthyroid atria instead of decrease. CNP-induced decrease
      in atrial ANP release was attenuated. Pretreatment with milrinone blocked the CNP
      induced increase of cAMP levels concomitantly with a decrease of atrial dynamics.
      The present study demonstrates that altered role of CNP-activated pGC-cGMP-PDE3
      cAMP signaling is involved in the pathophysiology of hyperthyroid heart.

PMID- 17531331
TI  - A comparison of the effects of gastrin, somatostatin and dopamine receptor
      ligands on rat gastric enterochromaffin-like cell secretion and proliferation.
AB  - Gastrin regulates ECL cell histamine release and is a critical determinant of
      acid secretion. ECL cell secretion and proliferation is inhibited by gastrin
      antagonists and somatostatin but little is known about the role of dopamine
      agonists in this process. Since the ECL cell exhibits all three classes of
      receptor we evaluated and compared the effects of the gastrin receptor
      antagonist, (YF476), lanreotide (SST agonist) and novel dopaminergic agents
      (BIM53061 and BIM27A760) on ECL cell histamine secretion and proliferation.
      Highly enriched (>98%) ECL cell preparations prepared from rat gastric mucosa
      using a FACS approach were studied. Real-time PCR confirmed presence of the CCK2,
      SS2 and SS5 and D1 receptors on ECL cells. YF476 inhibited histamine secretion
      and proliferation with IC(50)s of 1.25 nM and 1.3 x 10(-11) M respectively,
      values 10-1000x more potent than L365,260. Lanreotide inhibited secretion and
      proliferation (2.2 nM, 1.9 x 10(-10) M) and increased YF476-inhibited
      proliferation a further 5-fold. The dopamine agonist, BIM53061, inhibited gastrin
      mediated ECL cell secretion and proliferation (17 nM, 6 x 10(-10) M) as did the
      novel dopamine/somatostatin chimera BIM23A760 (22 nM, 4.9 x 10(-10) M). Our
      studies demonstrate that the gastrin receptor antagonist, YF476, is the most
      potent inhibitor of ECL cell histamine secretion and proliferation. Lanreotide, a
      dopamine agonist and a dopamine/somatostatin chimera inhibited ECL cell function
      but were 10-1000x less potent than YF476. Agents that selectively target the CCK2
      receptor may provide alternative therapeutic strategies for gastrin-mediated
      gastrointestinal cell secretion and proliferation such as evident in the
      hypergastrinemic gastric carcinoids associated with low acid states.

PMID- 17531332
TI  - Transmission parameters of highly pathogenic avian influenza (H7N1) among
      industrial poultry farms in northern Italy in 1999-2000.
AB  - We estimated between-farm transmission parameters of the highly pathogenic avian
      influenza (HPAI) epidemic that struck the poultry industry of northern Italy
      (including turkeys, layer hens, broilers, gamebirds, and waterfowl) from December
      1999 through April 2000. We estimated the average number of susceptible farms
      that were infected with HPAI virus by each infectious farm during a day (beta)
      with a generalised linear model (GLM). The HPAI's reproductive ratios (R(h); the
      average number of new infected farms (IFs) that were caused by an infectious
      farm) were calculated separately for the regions of Lombardy and Veneto, where
      382 out of 413 (92.5%) of IFs were located. In both regions, R(h) decreased to
      approximately 1 during the second month of the epidemic (showing that its
      containment had been initiated). Subsequently, during the last two months of the
      epidemic, beta and R(h) were reduced to 0.04/day and 0.6, respectively, in Veneto
      and to 0.07/day and 0.8 in Lombardy. The reduction of the susceptible population
      through strict control measures, including pre-emptive slaughter of at-risk
      poultry flocks, was implemented to a greatest extent in Veneto and this might
      have been associated with a more rapid control of the epidemic in this region
      than in Lombardy.

PMID- 17531333
TI  - Spatial clustering of swine influenza in Ontario on the basis of herd-level
      disease status with different misclassification errors.
AB  - This approach maximizes sensitivity of serology-based monitoring systems by
      considering spatial clustering of herds classified as false positive by herd
      testing, allowing outbreaks to be detected in an early phase. The primary
      objective of this study was to determine whether swine herds infected with
      influenza viruses cluster in space, and if so, where they cluster. The secondary
      objective was to investigate the combining of a multivariate spatial scan
      statistic with herd test results to maximize the sensitivity of the surveillance
      system for swine influenza. We tested for spatial clustering of swine influenza
      using the Cuzick-Edwards test as a global test. The location of the most likely
      spatial clusters of cases for each subtype and strain in a sample of 65 sow and
      72 finisher herds in 2001 (Ontario, Canada), and 76 sow herds in 2003 (Ontario,
      Canada) was determined by a spatial scan statistic in a purely spatial Bernoulli
      model based on single and multiple datasets. A case herd was defined by true herd
      disease status for sow or finisher herds tested for H1N1, and by apparent herd
      disease status for sow herds tested for two H3N2 strains (A/Swine/Colorado/1/77
      (Sw/Col/77) and A/Swine/Texas/4199-2/98 (Sw/Tex/98)). In sow herds, there was no
      statistically significant clustering of H1N1 influenza after adjustment for pig
      farm density. Similarly, spatial clustering was not found in finisher herds. In
      contrast, clustering of H3N2 Sw/Col/77 (prevalence ratio=12.5) and H3N2 Sw/Tex/98
      (prevalence ratio=15) was identified in an area close to a region with documented
      isolation of avian influenza isolates from pigs. For the H1N1 subtype tested by
      ELISA, we used an approach that minimized overall misclassification at the herd
      level. This could be more applicable for detecting clusters of positive farms
      when herd prevalence is moderate to high than when herd prevalence is low. For
      the H3N2 strains we used an approach that maximized herd-level sensitivity by
      minimizing the herd cut-off. This is useful in situations where prevalence of the
      pathogen is low. The results of applying a multivariate spatial scan statistic
      approach, led us to generate the hypothesis that an unknown variant of influenza
      of avian origin was circulating in swine herds close to an area where avian
      strains had previously been isolated from swine. Maximizing herd sensitivity and
      linking it with the spatial information can be of use for monitoring of pathogens
      that exhibit the potential for rapid antigenic change, which, consequently, might
      then lead to diminished cross-reactivity of routinely used assays and lower test
      sensitivity for the newly emerged variants. Veterinary authorities might
      incorporate this approach into animal disease surveillance programs that either
      substantiate freedom from disease, or are aimed at detecting early incursion of a
      pathogen, such as influenza virus, or both.

PMID- 17531334
TI  - EGFR-TK inhibition before radiotherapy reduces tumour volume but does not improve
      local control: differential response of cancer stem cells and nontumourigenic
      cells?
AB  - BACKGROUND AND PURPOSE: Waiting times before radiotherapy may reduce tumour
      control probability due to proliferation of tumour cells. The aim of the
      experiment was to test whether the growth inhibiting effect of epidermal growth
      factor receptor (EGFR)-inhibitors after surgery or tumour transplantation results
      in a lower tumour mass at time of irradiation and can thereby improve local
      tumour control. MATERIALS AND METHODS: The EGFR-tyrosine kinase inhibitor
      BIBX1382BS was applied over 14days starting from microscopically non-in-sano
      resection of FaDu tumours or from tumour transplantation, followed by irradiation
      (5f/5d). Endpoint was local tumour control. In addition, vital tumour areas,
      pimonidazole hypoxic fraction, BrdU labelling index, and colony forming ability
      in vitro were tested in control tumours and after BIBX1382BS treatment (starting
      from transplantation). RESULTS: The tumour volume at start of irradiation was
      significantly lower in the BIBX1382BS treated tumours as compared to the control
      groups by factors of 11 (post-surgery setting) and 2.7 (transplantation setting).
      However, the reduced volume did not translate into improved local control after
      irradiation. The TCD(50) values after surgery were 25.4Gy [95% CI 18; 33Gy] in
      the control group and 30.5Gy [24; 37] in the BIBX1382BS group (p=0.25). Treatment
      after transplantation resulted in TCD(50) values of 41.1Gy [35; 47] in the
      control group and 41.1Gy [33; 49] in the BIBX1382BS group (p=1). While the
      proportion of S-phase cells decreased after BIBX1382BS treatment, no differences
      were observed between the pimonidazole hypoxic fractions and in vitro colony
      forming ability. CONCLUSIONS: EGFR-TK inhibition with BIBX1382BS over 14days
      between macroscopically complete tumour resection or tumour transplantation and
      start of radiotherapy significantly reduced tumour volume but did not improve
      local tumour control. One possible explanation is that the EGFR-TK inhibitor has
      a higher activity in nontumourigenic cancer cells compared to cancer stem cells.
      This hypothesis, along with the observation that tumours of similar size were
      significantly more radiosensitive after surgery than without surgery, warrants
      further investigation.

PMID- 17531335
TI  - High dose rate brachytherapy in combination with external beam radiotherapy in
      the radical treatment of prostate cancer: initial results of a randomised phase
      three trial.
AB  - BACKGROUND AND PURPOSE: A randomised phase III trial has compared external beam
      radiotherapy alone with a dose escalated schedule using high dose rate
      brachytherapy. Patients with histologically confirmed prostate cancer, no
      evidence of metastases, a PSA <50, no previous TURP and fit for general
      anaesthetic were included. METHODS: Patients were randomised to receive either
      standard radiotherapy 55 Gy in 20 fractions treating Monday to Friday over 4
      weeks or a combined schedule comprising external beam treatment delivering 35.75
      Gy in 13 fractions treating daily Monday to Friday over 2.5 weeks followed by a
      temporary high dose rate afterloading implant delivering 17 Gy in two fractions
      over 24h. RESULTS: A total of 220 patients were randomised, balanced for
      important prognostic parameters including tumour stage, presenting PSA, Gleason
      score and use of adjuvant anti-androgens. With a median follow up of 30 months
      (range 3-91) a significant improvement in actuarial biochemical relapse-free
      survival is seen in favour of the combined brachytherapy schedule (p=0.03). A
      lower incidence of acute rectal discharge was seen in the brachytherapy group
      (p=0.025) and other acute and late toxicities were equivalent. Patients
      randomised to brachytherapy had a significantly better FACT-P score at 12 weeks
      (p=0.02). CONCLUSIONS: The use of high dose rate brachytherapy in combination
      with external beam radiotherapy resulted in an improved biochemical relapse-free
      survival compared to external beam radiotherapy alone with less acute rectal
      toxicity and improved quality of life in this randomised trial.

PMID- 17531336
TI  - Development and evaluation of a cetuximab-based imaging probe to target EGFR and
      EGFRvIII.
AB  - BACKGROUND AND PURPOSE: The epidermal growth factor receptor (EGFR) is
      overexpressed in a significant percentage of human malignancies and its
      expression is associated with tumour aggressiveness and treatment resistance. The
      monoclonal antibody cetuximab (IMC-C225) blocks the ligand-binding domain of EGFR
      with high affinity, preventing downstream signalling resulting in tumour growth
      inhibition. We developed and characterized a novel imaging probe using Oregon
      Green 488 labelled cetuximab to evaluate its usage as an imaging agent to target
      EGFR. MATERIALS AND METHODS: Cells with varying expression levels of EGFR or a
      mutant form of EGFR, called EGFRvIII, were used for in vitro validation. The in
      vivo binding of labelled cetuximab to EGFR was also assessed ex vivo on tumour
      material. RESULTS: The development of Oregon Green 488 labelled cetuximab was
      successful, demonstrating binding to both EGFR and EGFRvIII in vitro.
      Accumulation was also found in vivo, which was confirmed by histopathology using
      anti-EGFR antibodies. However, significant mismatch highlights differences
      between drug delivery in vivo, and cell expression levels of EGFR. CONCLUSIONS:
      The monoclonal antibody cetuximab represents a promising probe to evaluate the
      biologic and pharmacokinetic effects of in vivo cetuximab binding to EGFR. It not
      only visualizes the presence of the wild type EGFR, but also the presence of the
      mutant EGFRvIII.

PMID- 17531337
TI  - Phosphorylation of eIF2alpha is required for mRNA translation inhibition and
      survival during moderate hypoxia.
AB  - BACKGROUND AND PURPOSE: Human tumors are characterized by temporal fluctuations
      in oxygen tension. The biological pathways that respond to the dynamic tumor
      microenvironment represent potential molecular targets for cancer therapy. Anoxic
      conditions result in eIF2alpha dependent inhibition of overall mRNA translation,
      differential gene expression, hypoxia tolerance and tumor growth. The signaling
      pathway which governs eIF2alpha phosphorylation has therefore emerged as a
      potential molecular target. In this study, we investigated the role of eIF2alpha
      in regulating mRNA translation and hypoxia tolerance during moderate hypoxia.
      Since other molecular pathways that regulate protein synthesis are frequently
      mutated in cancer, we also assessed mRNA translation in a panel of cell lines
      from different origins. MATERIALS AND METHODS: Immortalized human fibroblast,
      transformed mouse embryo fibroblasts (MEFs) and cells from six cancer cell lines
      were exposed to 0.2% or 0.0% oxygen. We assayed global mRNA translation
      efficiency by polysome analysis, as well as proliferation and clonogenic
      survival. The role of eIF2alpha was assessed in MEFs harboring a homozygous
      inactivating mutation (S51A) as well as in U373-MG cells overexpressing GADD34 (C
      term) under a tetracycline-dependent promoter. The involvement of eIF4E
      regulation was investigated in HeLa cells stably expressing a short hairpin RNA
      (shRNA) targeting 4E-BP1. RESULTS: All cells investigated inhibited mRNA
      translation severely in response to anoxia and modestly in response to hypoxia.
      Two independent genetic cell models demonstrated that inhibition of mRNA
      translation in response to moderate hypoxia was dependent on eIF2alpha
      phosphorylation. Disruption of eIF2alpha phosphorylation caused sensitivity to
      hypoxia and anoxia. CONCLUSIONS: Disruption of eIF2alpha phosphorylation is a
      potential target for hypoxia-directed molecular cancer therapy.

PMID- 17531338
TI  - Homologous recombination and prostate cancer: a model for novel DNA repair
      targets and therapies.
AB  - Using elegant targeting techniques such as IMRT, radiation oncology has improved
      the therapeutic ratio of prostate cancer radiotherapy through increased physical
      precision (e.g. increased local control through dose-escalation without increased
      normal tissue toxicity). The therapeutic ratio might be further improved by the
      addition of "biologic precision and escalation" pertaining to the use of
      molecular inhibitors of DNA damage sensing and repair. Indeed, proteins involved
      in the ATM-p53 damage signaling axis and the homologous (HR) and non-homologous
      end-joining (NHEJ) pathways of DNA double-strand break (DNA-dsb) rejoining
      pathways may be attractive candidates to elucidate cancer risk, prognosis,
      prediction of response and to develop sensitizers towards oxic and hypoxic
      prostate tumor cells. This review highlights DNA-dsb in prostate cancer research
      in terms of novel molecular inhibitors, the role of the microenvironment in DNA
      dsb repair and potential DNA-dsb biomarkers for clinical trials.

PMID- 17531339
TI  - Acneiform rash secondary to cetuximab plus head and neck radiotherapy.

PMID- 17531340
TI  - Proteomic analysis of gene expression following hypoxia and reoxygenation reveals
      proteins involved in the recovery from endoplasmic reticulum and oxidative
      stress.
AB  - BACKGROUND AND PURPOSE: Human tumors are characterized by large variations in
      oxygen concentration and hypoxic tumors are associated with poor prognosis. In
      addition, tumors are subjected to periodic changes in oxygenation characterized
      by hypoxia followed by reoxygenation. Cellular adaptation to hypoxia is well
      documented, nevertheless little is known about adaptive mechanisms to
      reoxygenation. Here, we investigate the changes in protein expression during
      reoxygenation using proteomics. MATERIALS AND METHODS: HeLa cervix carcinoma
      cells were exposed to 4h of hypoxia (<0.01% O(2)) followed by 1h of
      reoxygenation. The cellular proteome was examined using 2D gel electrophoresis
      coupled with mass spectrometry. Validation and investigation of the underlying
      basis for induced protein expression was investigated using Western blot analysis
      and quantitative RT-PCR. RESULTS: We identified proteins involved in several
      cellular processes that are responsible for regulating RNA metabolism, protein
      synthesis and degradation, including ribosomal protein P0, VCP/p97 and FUSE
      binding protein 2. CONCLUSIONS: Our results suggest that these newly identified
      proteins function in pathways that may assist in the recovery of ER stress and
      protein synthesis during reoxygenation. These proteins may thus be important
      determinants of the behaviour and survival of tumor cells to transient hypoxic
      exposures.

PMID- 17531341
TI  - Stimulus intensity affects early sensory processing: sound intensity modulates
      auditory evoked gamma-band activity in human EEG.
AB  - We studied the effect of different sound intensities on the auditory evoked gamma
      band response (GBR). Previous studies observed oscillatory gamma activity in the
      auditory cortex of animals and humans. For the visual modality, it has been
      demonstrated that the GBR can be modulated by top-down (attention, memory) as
      well as bottom-up factors (stimulus properties). Therefore, we expected to find a
      sound intensity modulation for the auditory GBR. 21 healthy participants without
      hearing deficits were investigated in a forced-choice discrimination task.
      Sinusoidal tones were presented at three systematically varied sound intensities
      (30, 45, 60 dB hearing level). The results of the auditory evoked potentials were
      predominantly consistent with previous studies. Furthermore, we observed an
      augmentation of the evoked GBR with increasing sound intensity. The analysis
      indicated that this intensity difference in the GBR amplitude most likely arises
      from increased phase-locking. The results demonstrate a distinct dependency
      between sound intensity and gamma-band oscillations. Future experiments that
      investigate the relationship between auditory evoked GBRs and higher cognitive
      processes should therefore select stimuli with an adequate sound intensity and
      control this variable to avoid confounding effects. In addition, it seems that
      gamma-band activity is more sensitive to exogenous stimulus parameters than
      evoked potentials.

PMID- 17531342
TI  - Expansion of formalin-evoked Fos-immunoreactivity in rats with a spinal cord
      injury.
AB  - Peripheral tissue injury as well as spinal cord injury (SCI) may lead to
      sensitization of dorsal horn neurons and alterations in nociceptive processing.
      Thus, peripheral injuries experienced by SCI patients, even if not initially
      perceived, could result in a persistent and widespread activation of dorsal horn
      neurons and emerge as chronic pain with interventive repair or modest recovery
      from SCI. To visualize the spinal neuron response to peripheral tissue injury
      following complete SCI in rats, the neural transcription factor Fos was
      quantitated in the spinal cord. Two weeks following either a complete transection
      of the spinal cord at the level of T8 or a sham surgery (laminectomy), rats were
      injected with formalin into the left hind paw. Sham-operated rats demonstrated
      biphasic hind paw pain-related behavior following formalin injection, but
      transected rats displayed fewer behaviors in the second (tonic) phase.
      Stereological analysis of the sham group revealed that the extent of formalin
      induced Fos expression was within the lumbar dorsal horn, with numerous Fos-like
      immunoreactive profiles in the ipsilateral dorsal horn and some contralateral
      immunoreactive profiles. In contrast, the level of Fos-like immunoreactivity in
      the transected group was significantly elevated and expanded in range compared to
      the sham group, with increases observed in the normal laminar distribution
      regions, as well as multi-segmentally through sacral levels and increases in the
      contralateral dorsal horn segments. The data demonstrate that widespread
      activation of spinal, especially dorsal horn, neurons following peripheral insult
      can occur in the injured spinal cord, despite reduced pain responsiveness, and
      suggests that exaggerated pain may emerge as spinal recovery or repair
      progresses.

PMID- 17531343
TI  - Diversity and killer behaviour of indigenous yeasts isolated from the
      fermentation vat surfaces in four Patagonian wineries.
AB  - The diversity and killer behaviour of the yeast biota associated with surfaces of
      four Patagonian wineries were analyzed in the present study. These wineries were
      different in their technological and ecological features. Following liquid
      enrichment of samples from fermentation vat surfaces yeast isolates were
      identified by pheno- and genotyping and characterized using killer sensitivity
      patterns. Out of 92 isolated yeasts, 25% were Saccharomyces cerevisiae; 18% were
      Kloeckera apiculata and 11% were Pichia anomala; other six species representing a
      low percentage were also found. A particular biota composed mainly by S.
      cerevisiae (57%) and P. anomala (37%) was found in the winery located far from
      the other three wineries. As a whole, the wineries using spontaneous fermentation
      showed a major percentage of S. cerevisiae and a minor percentage of K.
      apiculata. The present study showed a pronounced heterogeneity in killer
      behaviour: killer, 35%, neutral, 25% and sensitive, 40%. In particular, S.
      cerevisiae isolates showed a higher sensitivity to killer reference yeasts than
      non-Saccharomyces isolates. On the other hand, most of the non-Saccharomyces
      yeasts isolated from fermentation vats were resistant to Saccharomyces toxins.

PMID- 17531344
TI  - Inhibition of HCV RNA-dependent RNA polymerase activity by aqueous extract from
      Fructus Ligustri Lucidi.
AB  - The development of effective antiviral drugs against hepatitis C virus (HCV)
      continues to be needed, since neither vaccines nor broadly effective therapeutic
      agents are available. HCV RNA-dependent RNA polymerase (NS5B) is strictly
      required for viral replication and thus represents an attractive target. Here,
      aqueous extracts from five traditional Chinese medicines were tested for their
      ability to inhibit NS5B activity by reporter assays using cell-based NS5B
      activity detecting systems. Among them, aqueous extract from Fructus Ligustri
      Lucidi exhibited a promising result, dose-dependent inhibition of the luciferase
      activity, an indicator of intracellular NS5B activity (p<0.001), in the absence
      of cytotoxicity. Further Quantitative RT-PCR assays and Western blot analysis
      showed aqueous extract from Fructus Ligustri Lucidi inhibited intracellular NS5B
      catalyzed RNA synthesis dose-dependently (p<0.001) without affecting
      intracellular NS5B expression. Subsequent in vitro NS5B assays revealed that this
      extract could directly inhibit NS5B activity. Taken together, these results
      indicated that Fructus Ligustri Lucidi might offer a promising source of
      antiviral drugs against HCV NS5B. Purification of the active compound(s) and
      antiviral effect are clearly required in the future.

PMID- 17531345
TI  - Mumford-Shah algorithm applied to videokeratography image processing and
      consequences to refractive power values.
AB  - There are many corneal diseases that can be detected using an eye-care device
      called videokeratograph. The videokeratograph is based on the principle of an
      apparatus called Placido disc and is used to precisely measure the anterior
      surface of the cornea. This disc contains rings alternately white and black,
      which are reflected on the patient's cornea during the examination. The device
      can find anomalies by analyzing the reflected image, using image-processing
      algorithms. Although the efficiency of most commercial videokeratographs is
      acceptable, manufacturers do not disseminate to the scientific community the
      technique used in the image analysis algorithms. This makes it difficult for the
      specialized researcher in order to find better algorithms for the image
      processing and, consequently, increase the instrument's precision. In this work
      we have segmented the Placido disc in polar coordinates by implementing a
      diagonal section of the image, in the radial direction. The objective is to find
      the inflection points in the signal obtained. In this paper the signal is studied
      by using the Mumford-Shah segmentation method. The results are compared to those
      obtained with other classic methods in the literature, e.g. Marr-Hildreth
      filters, numerical derivative, Fourier derivative, morphological Laplacian and
      Canny derivative. The best result was achieved by using the Mumford-Shah
      functional. Using this technique it was possible to find the inflection positions
      with higher accuracy. The method did not detect any false inflection. Mumford
      Shah's method demonstrated also a high precision in the task of eliminating
      noises from the original signal.

PMID- 17531346
TI  - The O3-Vet project: a veterinary electronic patient record based on the web
      technology and the ADT-IHE actor for veterinary hospitals.
AB  - A veterinary electronic patient record, compliant with the IT standards (HL7,
      DICOM and IHE), was developed at the School of Veterinary Medicine, University of
      Milan (Italy) in order to improve the veterinary hospital workflows, making the
      stored clinical data more homogenous and sharable, thereby increasing the
      integration with current and future software applications. The system was
      developed by open-source software in order to reduce the implementation and
      maintenance costs and to make the system sharable with other veterinary hospitals
      or research centers without additional costs. The system was tested from May to
      October 2006. Results show that the majority of the veterinarians involved in the
      test agreed on the advantages obtained by the use of application software
      concerning the availability of all the useful clinical data [71.4%], the quality
      of the diagnostic procedures [78.58%] and the efficiency [85.58%] of hospital
      activities.

PMID- 17531347
TI  - Meta-modeling of the pesticide fate model MACRO for groundwater exposure
      assessments using artificial neural networks.
AB  - Several simple index methods that use easily accessible data have been developed
      and included in decision-support systems to estimate pesticide leaching across
      larger areas. However, these methods often lack important process descriptions
      (e.g. macropore flow), which brings into question their reliability. Descriptions
      of macropore flow have been included in simulation models, but these are too
      complex and demanding for spatial applications. To resolve this dilemma, a neural
      network simulation meta-model of the dual-permeability macropore flow model MACRO
      was created for pesticide groundwater exposure assessment. The model was
      parameterized using pedotransfer functions that require as input the clay and
      sand content of the topsoil and subsoil, and the topsoil organic carbon content.
      The meta-model also requires the topsoil pesticide half-life and the soil organic
      carbon sorption coefficient as input. A fully connected feed-forward multilayer
      perceptron classification network with two hidden layers, linked to fully
      connected feed-forward multilayer perceptron neural networks with one hidden
      layer, trained on sub-sets of the target variable, was shown to be a suitable
      meta-model for the intended purpose. A Fourier amplitude sensitivity test showed
      that the model output (the 80th percentile average yearly pesticide concentration
      at 1 m depth for a 20 year simulation period) was sensitive to all input
      parameters. The two input parameters related to pesticide characteristics (i.e.
      soil organic carbon sorption coefficient and topsoil pesticide half-life) were
      the most influential, but texture in the topsoil was also quite important since
      it was assumed to control the mass exchange coefficient that regulates the
      strength of macropore flow. This is in contrast to models based on the advection
      dispersion equation where soil texture is relatively unimportant. The use of the
      meta-model is exemplified with a case-study where the spatial variability of
      pesticide leaching is mapped for a small field. It was shown that the area of the
      field that contributes most to leaching depends on the properties of the compound
      in question. It is concluded that the simulation meta-model of MACRO should prove
      useful for mapping relative pesticide leaching risks at large scales.

PMID- 17531348
TI  - Fast and frugal food choices: uncovering individual decision heuristics.
AB  - Research on food decision making is often based on the assumption that people
      take many different aspects into account and weight and add them according to
      their personally assessed importance. Yet there is a growing body of research
      suggesting that people's decisions can often be better described by simple
      heuristics-rules of thumb that people use to make choices based on only a few
      important pieces of information. To test empirically whether a simple heuristic
      is able to account for individual food decisions, we ran a computerized
      experiment in which participants (N = 50) repeatedly chose between pairs of 20
      lunch dishes that were sampled from a local food court. A questionnaire assessed
      individual importance weights as well as evaluation ratings of each lunch dish on
      nine different factors. Our results show that a simple lexicographic heuristic
      that only considers each participant's most important factors is as good at
      predicting participants' food choices as a weighted additive model that takes all
      factors into account. This result questions the adequacy of weighted additive
      models as sole descriptions of human decision making in the food domain and
      provides evidence that food choices may instead be based on simple heuristics.

PMID- 17531349
TI  - Repairing brain after stroke: a review on post-ischemic neurogenesis.
AB  - Stroke is devastating as currently no therapies are available that can prevent
      stroke-induced neurological dysfunction in humans. With the recent observations
      that acute insults to adult brain stimulate new neuronal formation in various
      species of animals, optimism is building for a possible regeneration of stroke
      damaged brain. This article reviewed the advances in the understanding of the
      molecular mechanisms of the various steps of neurogenesis with an emphasis on the
      endogenous mediators and exogenous promoters of neural progenitor proliferation,
      migration and survival in the post-ischemic adult brain.

PMID- 17531350
TI  - Hydrogen peroxide attenuates insulin-like growth factor-1 neuroprotective effect,
      prevented by minocycline.
AB  - Oxidative stress-induced neuronal death due to hydrogen peroxide overload plays a
      critical role in the pathogenesis of numerous neurological diseases. Insulin-like
      growth factor-1 (IGF-1) is important in maintaining neuronal survival,
      proliferation, and differentiation in the central nervous system. We now report
      that sublethal doses of hydrogen peroxide attenuated IGF-1 neuroprotective
      activity on cultured cerebellar granule neurons under potassium and serum
      deprivation. Interestingly, this attenuation can be prevented by minocycline, an
      antibiotic that has been shown to have neuroprotective activity in animal models
      of neuronal injury. Furthermore, hydrogen peroxide also blocked IGF-1's
      neuroprotection for cortical neurons deprived of neurotrophic factors (B27),
      which was prevented by minocycline. Our data suggest that inhibition of IGF-1
      signaling by hydrogen peroxide may constitute an additional pathway contributing
      to its neurotoxicity. More importantly, combining minocycline and IGF-1 could be
      an effective treatment in neurological diseases associated with both oxidative
      stress and deficiency of IGF-1.

PMID- 17531351
TI  - Treatment of hypoxic-ischemic encephalopathy in mouse by transplantation of
      embryonic stem cell-derived cells.
AB  - A 7-day-old hypoxic-ischemic encephalopathy (HIE) mouse model was used to study
      the effect of transplantation of embryonic stem (ES) cell-derived cells on the
      HIE. After the inducement in vitro, the ES cell-derived cells expressed Nestin
      and MAP-2, rather than GFAP mRNA. After transplantation, ES cell-derived cells
      can survive, migrate into the injury site, and specifically differentiate into
      neurons, showing improvement of the learning ability and memory of the HIE mouse
      at 8 months post-transplantation. The non-grafted HIE mouse brain showed typical
      pathological changes in the hippocampus and cerebral cortex, where the number of
      neurons was reduced, while in the cell graft group, number of the neurons
      increased in the same regions. Although further study is necessary to elucidate
      the precise mechanisms responsible for this functional recovery, we believe that
      ES cells have advantages for use as a donor source in HIE.

PMID- 17531352
TI  - Differential temporal response of hippocampus, cortex and cerebellum to hypobaric
      hypoxia: a biochemical approach.
AB  - Hypobaric hypoxia is known to cause cognitive dysfunctions and memory impairment.
      The present study aimed at exploring the occurrence of oxidative stress in
      hypobaric hypoxia and the differential temporal response of the hippocampus,
      cerebellum following hypobaric hypoxia. Animals were divided into control, 3
      days, 7 days and 14 days exposure groups and were exposed to an altitude of
      25,000 ft. Our study revealed an increase in lactate dehydrogenase activity along
      with increase in free radical generation and lipid peroxidation. We also noted
      depletion in the antioxidants and decrease in glutathione reductase and
      superoxide dismutase activity. There was significant decrease in reduced
      glutathione levels in the exposure groups when compared to the control which was
      accompanied by a concomitant increase in oxidized glutathione levels. Increase in
      glutamate dehydrogenase activity was observed coinciding with the decrease in
      glutathione levels which was accompanied with an increase in expression of
      vesicular glutamate transporter. The hippocampus was found to be more vulnerable
      to hypobaric hypoxia-induced oxidative stress in comparison to the cortex and
      cerebellum. An interesting observation was the onset of acclimatization on
      prolonged exposure to hypobaric hypoxia for a period of 14 days. Hypobaric
      hypoxia was found to affect various regions of the brain differentially and the
      response of each region varied as a function of time.

PMID- 17531353
TI  - Loss of VGLUT1 and VGLUT2 in the prefrontal cortex is correlated with cognitive
      decline in Alzheimer disease.
AB  - Several lines of evidence suggest that the glutamatergic system is severely
      impaired in Alzheimer disease (AD). Here, we assessed the status of glutamatergic
      terminals in AD using the first available specific markers, the vesicular
      glutamate transporters VGLUT1 and VGLUT2. We quantified VGLUT1 and VGLUT2 in the
      prefrontal dorsolateral cortex (Brodmann area 9) of controls and AD patients
      using specific antiserums. A dramatic decrease in VGLUT1 and VGLUT2 was observed
      in AD using Western blot. Similar decreases were observed in an independent group
      of subjects using immunoautoradiography. The VGLUT1 reduction was highly
      correlated with the degree of cognitive impairment, assessed with the clinical
      dementia rating (CDR) score. A significant albeit weaker correlation was also
      observed with VGLUT2. These findings provide evidence indicating that
      glutamatergic systems are severely impaired in the A9 region of AD patients and
      that this impairment is strongly correlated with the progression of cognitive
      decline. Our results suggest that VGLUT1 expression in the prefrontal cortex
      could be used as a valuable neurochemical marker of dementia in AD.

PMID- 17531354
TI  - Synthesis, determination of the lipophilicity, anticancer and antimicrobial
      properties of some fused 1,2,4-triazole derivatives.
AB  - 3-Unsubstituted and 3-substituted-7-aryl-5H-6,7-dihydroimidazo[2,1
      c][1,2,4]triazoles (1-14) were designed and obtained from biologically active 1
      aryl-2-hydrazonoimidazolidines by cyclocondensation reaction with triethyl
      orthoformates (1-4), phenoxyacetic acid derivatives (5-13) and carbon disulfide
      (14), respectively. Their chemical structures were confirmed by IR, (1)H NMR,
      (13)C NMR, MS spectra and elemental analysis. In the high performance liquid
      chromatographic series of experiments, fourteen synthesized compounds (1-14) were
      chromatographed on octadecyl silica adsorbent and their lipophilicity parameter
      (logk(W)) was determined using various aqueous systems: mixture of water and
      organic modifiers (methanol - MeOH, acetonitrile - MeCN or dioxane - DX).
      Compounds 7 and 12 were evaluated for their cytotoxic activity against three
      cancer cell lines: human Caucasian colon adenocarcinoma cell line - LS180 (ECACC
      87021202), human uterus carcinoma cell line - SiHa (ECACC 85060701) and human
      breast carcinoma cell line - T47D (ECACC 85102201). Compound 12 was found to be
      the most effective in vitro against human colon adenocarcinoma cell line (LS180).
      Moreover, the distinctly marked lower cytotoxicity of compounds 7 and 12 against
      the normal cell line - human skin fibroblasts (HSF) and almost several-fold
      higher against the examined cancer cell lines was ascertained. The cytotoxic
      effect of imidazotriazole 7 was noticed on DNA structure of breast cancer cell
      line (T47D) by using the comet assay. Compound 7 in concentration of 29.3 microM
      was found to possess efficiency for DNA strand breakage. In particular, this led
      to cutting of the DNA strands and formation of small fragments of DNA - two
      higher and one lighter in comparison with control DNA. Moreover, significant
      viability decreases in the human leukaemic RPMI 8226 cells treated with different
      concentrations of imidazotriazoles 8-12 were observed, suggesting their
      antiproliferative properties. Besides, three tested compounds (9, 13, 14)
      revealed significant antimicrobial activities with MIC values in the range of
      30.9-44.0 microM. Compound 13 showed superior antibacterial activity to
      ampicillin and chloramphenicol in vitro, whereas 14 displayed superior antifungal
      activity to miconazole.

PMID- 17531355
TI  - Rapid emergence of a viral resistant mutant in WHV chronically infected
      woodchucks treated with lamivudine and a pre-S/S CHO-derived hepatitis B virus
      vaccine.
AB  - To determine whether the addition of a pre-S/S human vaccine increases the
      antiviral activity of lamivudine, four woodchucks were treated with a daily dose
      of 100 mg/kg lamivudine and four 50 microg doses of CHO-derived pre-S/S human
      vaccine. WHV DNA titres decreased up to two logarithms in three woodchucks. At
      week 4, in three of the animals, the sequence analysis showed a predominant
      strain containing a nucleotide change from A to T at position 1696 of domain B of
      the WHV DNA polymerase. Vaccination did not further suppress WHV DNA, despite
      anti-HBs production in three animals. The woodchuck remains a useful model for
      characterising the biology and kinetics of the emergence of drug-resistant
      variants and could be used for pre-clinical studies of combinations of new
      antiviral drugs.

PMID- 17531356
TI  - Effect of the purification process and the storage conditions on the efficacy of
      an inactivated vaccine against heartwater.
AB  - This work evaluates the effect of purification process and storage conditions
      (buffer formulation and temperature) on the efficacy of Ehrlichia ruminantium
      (ER) elementary bodies to be used as an inactivated vaccine candidate against
      heartwater. In vitro assays revealed that, to avoid major losses in ER integrity
      and corresponding antigenic properties, a buffer with pH between 5.6 and 8 and an
      osmolality above 100 mOsmol/kg H(2)O is recommended. Amongst the tested
      formulations, both PBS and NaCl have shown to stabilize ER antigens at -20
      degrees C. To assess the protective properties of the different vaccine
      formulations, in vivo experiments were performed using a goat model. The results
      obtained showed that the preparation of ER antigens using a novel membrane-based
      purification strategy and a simple vaccine formulation (NaCl, -20 degrees C)
      induced equivalent protection to the conventional vaccine based on ER antigens
      prepared by a multistep centrifugation methodology and stored at -20 degrees C in
      PBS buffer.

PMID- 17531357
TI  - Genetic diversification of Neisseria meningitidis during waves of colonization
      and disease in the meningitis belt of sub-Saharan Africa.
AB  - Although Neisseria meningitidis is a highly variable organism, most invasive
      disease is caused by a minority of genotypes. Hypervirulent lineages have been
      identified and their pandemic spread has been traced. During a longitudinal
      meningococcal colonization study in a district of northern Ghana clonal waves of
      carriage and disease were observed. Genetic diversification of genoclouds was
      analysed by pulsed field gel electrophoretic (PFGE) analysis of isolates from
      healthy carriers and from meningitis patients. Even during the limited time of
      persistence in the district, microevolution of the dominating genoclouds took
      place. Population genomic analyses are required to understand the genetic basis
      for the emergence of new lineages with epidemic potential, which is of crucial
      importance for the development of long-term global vaccination strategies against
      meningococcal disease.

PMID- 17531358
TI  - Peptides coupled to the surface of a kind of liposome protect infection of
      influenza viruses.
AB  - In our previous study, OVA conjugated on the surface of a liposome, we termed
      Oleoyl liposome, which consisted of dioleoyl phosphatidyl choline, dioleoyl
      phosphatidyl ethanolamine, dioleoyl phosphatidyl glycerol acid and cholesterol in
      a 4:3:7:2 molar ratio, induced OVA-specific IgG antibody production but not OVA
      specific IgE antibody production that is detrimental to the host. Furthermore,
      OVA(257-264)-Oleoyl liposome elicited CTL responses in the presence of CpG and
      rejected E.G7 tumors in mice. In this study we tested whether a peptide-Oleoyl
      liposome conjugates are capable of inducing protection against viral growth.
      Subcutaneous inoculation of NP(366-374)-Oleoyl liposome with CpG inhibited growth
      of influenza viruses in lungs of mice. Thus, surface-linked liposomal peptide
      might serve as an effective vaccine without detrimental effects in the presence
      of immune potentiators.

PMID- 17531359
TI  - A blowfly strike vaccine requires an understanding of host-pathogen interactions.
AB  - The phase-out of Mulesing by 2010 means the Australian wool industry requires
      immediate and viable alternatives for the control and prevention of blowfly
      strike, an economically important parasitic disease of sheep. In this review we
      have analysed previous research aimed toward the development of a vaccine against
      blowfly strike and the reasons why the approaches taken were unsuccessful at the
      time. Close scrutiny has provided new insight into this host-parasite interaction
      and identified new opportunities for the development of a vaccine. Here we
      propose that addressing immunosuppression together with the induction of cellular
      immunity is likely to result in an anti-blowfly strike vaccine, as opposed to the
      use of "standard" approaches aimed at inducing humoral immunity.

PMID- 17531360
TI  - Immunization of mice with DNA coding for the variable regions of anti-idiotypic
      antibody generates antigen-specific response.
AB  - Understanding the mechanisms of generation and maintenance of immunological
      memory is crucial for rational vaccine design. A hypothesis known as relay
      hypothesis was earlier proposed which explains the maintenance of immunological
      memory through interaction of idiotypic and anti-idiotypic lymphocytes. In the
      present study, we have shown that immunization with rinderpest virus
      hemagglutinin protein specific anti-idiotypic antibody (Ab(2)v(beta)) DNAs coding
      for heavy and light chains generates antigen-specific antibody and T cell
      responses as well as Ab1 specific T cell response. We further show that boosting
      with the recombinant Ab(2)-vbeta proteins generates B and T cell memory response
      specific for antigen in anti-id DNA primed mice. This study provides experimental
      evidence for perpetuation of immunological memory through idiotypic network
      interactions.

PMID- 17531361
TI  - A modified technique of radial forearm free flap anastomosis.

PMID- 17531362
TI  - The use of epidural analgesia in lower limb free flap harvest.

PMID- 17531363
TI  - An in vivo investigation of ulnar nerve sliding during upper limb movements.
AB  - BACKGROUND: Peripheral nerves straighten and stretch in order to accommodate
      increases in bed length during joint movements. The ulnar nerve is predicted to
      show large bed length changes, particularly on elbow flexion. The present study
      examines sliding of the ulnar nerve during limb movements, to determine how far
      these changes are accommodated by straightening and stretch. METHODS: Ultrasound
      imaging was used to measure longitudinal nerve sliding in the forearm and upper
      arm during 40 degrees wrist extension, 90 degrees elbow flexion and 50 degrees
      shoulder abduction. Nerve trunk folding in the upper arm was measured from still
      ultrasound images taken in a series of limb positions from 40 degrees shoulder
      abduction, elbow extended and wrist neutral to full elbow flexion, 90 degrees
      shoulder abduction and wrist extension, a position designed to stretch the ulnar
      nerve. FINDINGS: Wrist extension led to clear nerve sliding in the forearm with
      movements of up to 4 mm. However, shoulder abduction and elbow flexion caused
      remarkably little nerve movement. Images of the ulnar nerve showed considerable
      curvature with 40 degrees shoulder abduction and elbow extension but a much
      straighter path with the elbow flexed. INTERPRETATION: The ulnar nerve appears
      unloaded and follows a wavy path in most functional upper limb positions. During
      elbow and shoulder movements, changes in bed length appear to be accommodated
      largely by straightening of the nerve path, with only modest stretch of the nerve
      itself when the elbow flexes. The ulnar nerve is thus well adapted for the large
      changes in bed length that occur during limb movements.

PMID- 17531364
TI  - Loading characteristics of females exhibiting excessive valgus moments during
      cutting.
AB  - BACKGROUND: Excessive knee valgus moments are considered a risk factor for non
      contact anterior cruciate ligament injuries in female athletes, however, little
      is known about the biomechanical factors that contribute to this loading pattern.
      The purpose of this study was to compare lower extremity kinematics, foot
      position and ground reaction forces between female soccer players who demonstrate
      normal frontal plane moments at the knee with those who demonstrate excessive
      frontal plane moments at the knee during a cutting maneuver. METHODS: Sixty-one
      female soccer players, 16 (2) years, participated. Three dimensional kinematics
      and ground reaction forces were recorded during a side-step cutting maneuver.
      Knee frontal plane moments were calculated with inverse dynamics equations and
      were used to classify subjects into normal (N=38) and excessive valgus moment
      (N=23) groups. FINDINGS: Data revealed that the subjects with excessive valgus
      moments demonstrated an initial loading pattern that included greater laterally
      directed ground reaction forces (P<0.001, effect size 1.51), increased hip
      abduction (P=0.002, effect size 0.79), increased hip internal rotation (P=0.008,
      effect size 0.71) and a more internally rotated foot progression angle (P=0.04,
      effect size 0.55). Taken together, these variables explained 49% of the variance
      in peak knee valgus moment (R=.698, P<0.001). INTERPRETATION: These results
      provide insight into potentially injurious loading strategies and support the
      premise that interventions designed to encourage loading of the lower extremity
      in a more neutral alignment may work to decrease frontal plane loading at the
      knee.

PMID- 17531365
TI  - Clinical predictors of response to cognitive-behavioral therapy for obsessive
      compulsive disorder.
AB  - This paper reviews predictors of treatment response in open and controlled trials
      of cognitive-behavioral therapy for obsessive-compulsive disorder (OCD). We focus
      on demographic characteristics, aspects of OCD symptoms, comorbidity, family
      factors, cognitive influences, and treatment-specific characteristics as
      predictor variables. Although inconsistent findings characterize much of the
      literature, several relatively consistent and salient predictors have emerged,
      including symptom severity, symptom subtype, severe depression, the presence of
      comorbid personality disorders, family dysfunction, and the therapeutic alliance.
      Implications of findings and recommendations for future research are discussed.

PMID- 17531366
TI  - [Thoughts on the Revue de Chirurgie Plastique (1931-34) and the Revue de
      Chirurgie Structive (1935-38)].
AB  - The history of modern plastic surgery starts when a young, restless ENT man, Dr
      M. Coelst, started a training in Plastic Surgery with Sebileau in Paris and
      Joseph in Berlin. This man of vision and far-sighted imagination realized that
      the separated efforts and publications of so many pioneers, scaterred all over
      the world, would be lost if not gathered in a scientific journal only devoted to
      plastic surgery for the benefit of all. This brought him to the idea of
      establishing, in 1931, at his own initiative, the first international Journal of
      Plastic Surgery ever published, the Revue de Chirurgie Plastique, fifteen years
      before the USA Journal Plastic and Reconstructive Surgery and sixteen years
      before the British Journal of Plastic Surgery. The name of the journal was
      changed in 1935 to the Revue de Chirurgie Structive. Coelst' Revue was promptly
      accepted as the leading Journal of Plastic Surgery and all the internationally
      known plastic Surgeons contributed to it by scientific papers of great value,
      even today.

PMID- 17531367
TI  - Prehibernation and hibernation effects on the D-3-hydroxybutyrate dehydrogenase
      of the heavy and light mitochondria from liver jerboa (Jaculus orientalis) and
      related metabolism.
AB  - The D-3-hydroxybutyrate dehydrogenase (BDH) (EC 1.1.1.30) from liver jerboa
      (Jaculus orientalis), a ketone body converting enzyme in mitochondria, in two
      populations of mitochondria (heavy and light) has been studied in different
      jerboa states (euthermic, prehibernating and hibernating). The results reveal:
      (1) important variations between states in terms of ketones bodies, glucose and
      lipid levels; (2) significant differences between the BDH of the two
      mitochondrial populations in term of protein expression and kinetic properties.
      These results suggest that BDH leads an important conformational change depending
      on the physiological state of jerboa. This BDH structural change could be the
      consequence of the lipid composition modifications in inner mitochondrial
      membrane leading to changes in BDH catalytic properties.

PMID- 17531368
TI  - The dynamics of signaling at the histaminergic photoreceptor synapse of
      arthropods.
AB  - Histamine, a ubiquitous aminergic messenger throughout the body, also serves as a
      neurotransmitter in both vertebrates and invertebrates. In particular, the
      photoreceptors of adult arthropods use histamine, modulating its release to
      signal increases and decreases in light intensity. Strong evidence from various
      arthropod species indicates that histamine is synthesized and stored in
      photoreceptors, undergoes Ca-dependent release, inhibits postsynaptic
      interneurons by gating Cl channels, and is then recycled. In Drosophila, the
      synthetic enzyme, histidine decarboxylase, and the subunits of the histamine
      gated chloride channel have been cloned. Possible histamine transporters at
      synaptic vesicles and for reuptake remain elusive. Indeed, the mechanisms that
      remove histamine from the synaptic cleft, and that help terminate histamine's
      action, are unexpectedly complex, their details remaining unresolved. A major
      pathway in Drosophila, and possibly other arthropod species, is by conjugation of
      histamine to beta-alanine to form carcinine in adjacent glia. This conjugate then
      returns to the photoreceptors where it is hydrolysed to liberate histamine, which
      is then loaded into synaptic vesicles. Evidence from other species suggests that
      direct reuptake of histamine into the photoreceptors may also occur. Light
      depolarizes the photoreceptors, causing histamine release and postsynaptic
      inhibition; dimming hyperpolarizes the photoreceptors, causing a decrease in
      histamine release and an "off" response in the postsynaptic cell. Further pursuit
      of histamine's action at these highly specialized synapses should lead to an
      understanding of how they signal minute changes in presynaptic membrane
      potential, how they reliably extract signals from noise, and how they adapt to a
      wide range of presynaptic membrane potentials.

PMID- 17531369
TI  - Effect of prototypic drugs ibuprofen and warfarin on global chaotropic unfolding
      of human serum heme-albumin: a fast-field-cycling 1H-NMR relaxometric study.
AB  - Human serum albumin (HSA) is the most prominent protein in plasma, but it is also
      found in tissues and secretions throughout the body. The three-domain design of
      HSA provides a variety of binding sites for many ligands, including heme and
      drugs. HSA has been used as a model multidomain protein to investigate how
      interdomain interactions affect the global folding/unfolding process. Here, we
      report on the reversible chemical denaturation of heme-HSA involving three
      different conformational states (F, N, and B, occurring at pH 4.0, 7.0, and 9.0,
      respectively) and on the effect of prototypic drugs ibuprofen and warfarin on
      thermodynamics of the reversible unfolding process. Chaotropic unfolding of heme
      HSA in the F, N, and B conformations is governed by different thermodynamic
      regimes, with the B form showing an entropic stabilization of the structure that
      compensates an enthalpic destabilization, and the F form easily unfolding under
      entropic control. Warfarin and ibuprofen binding stabilizes heme-HSA in both N
      and B states.

PMID- 17531370
TI  - AT-dependent luminescence of DNA-threading ruthenium complexes.
AB  - Whereas the emission from the ruthenium complex deltadelta-[mu
      bidppz(phen)4Ru2]4+ (P) is five times larger when intercalated into poly(dAdT)2
      than when intercalated into ct-DNA, the homologue deltadelta-[mu
      bidppz(bipy)4Ru2]4+ (B) has a smaller quantum yield and a red-shifted emission.
      The origin of this difference is here investigated by studying intercalation into
      oligonucleotides containing a central AT-tract. Increasing the length of the AT
      tract increases the emission quantum yield for P but decreases it for B. However,
      not even four helix turns of AT base pairs is enough to mimic poly(dAdT)2. B and
      P thus use the increased flexibility with increasing length of the AT-tract in
      opposite ways, whereas B gets more prone to quenching by water, P gets more
      protected from quenching. The earlier reported gradual increase of the
      intercalation rate with AT-stretch length is thus paralleled by a gradual change
      in the equilibrium properties of the intercalated state.

PMID- 17531371
TI  - Variability of soil-water quality due to Tsunami-2004 in the coastal belt of
      Nagapattinam district, Tamilnadu.
AB  - In this study, the Tsunami-caused deterioration of soil and groundwater quality
      in the agricultural fields of coastal Nagapattinam district of Tamilnadu state in
      India is presented by analyzing their salinity and sodicity parameters. To
      accomplish this, three sets of soil samples up to a depth of 30 cm from the land
      surface were collected for the first six months of the year 2005 from 28
      locations and the ground water samples were monitored from seven existing dug
      wells and hand pumps covering the study region at intervals of 3 months. The EC
      and pH values of both the soil and ground water samples were estimated and the
      spatial and temporal variability mappings of these parameters were performed
      using the geostatistical analysis module of ArcGIS((R)). It was observed that the
      spherical semivariogram fitted well with the data set of both EC and pH and the
      generated kriged maps explained the spatial and temporal variability under
      different ranges of EC and pH values. Further, the recorded EC and pH data of
      soil and ground water during pre-Tsunami periods were compared with the collected
      data and generated variability soil maps of EC and pH of the post-Tsunami period.
      It was revealed from this analysis that the soil quality six months after the
      Tsunami was nearing the pre-Tsunami scenario (EC< 1.5 dS m(-1); pH<8), whereas
      the quality of ground water remained highly saline and unfit for irrigation and
      drinking. These observations were compared with the ground scenarios of the study
      region and possible causes for such changes and the remedial measures for taking
      up regular agricultural practices are also discussed.

PMID- 17531372
TI  - A methodology of characterizing status and trend of land changes in oases: a case
      study of Sangong River watershed, Xinjiang, China.
AB  - Land change is often studied with Markov models to develop a probability
      transition matrix. The existing methods dependent on such matrixes cannot
      effectively characterize some important aspects associated with land change such
      as status, direction, trend and regional variations. This study presents
      mathematical models to quantify these elements, defining unbalanced, quasi
      balanced and balanced status, one- and two-way transitions and the rising or
      falling trends. Using these models and remote-sensing imageries, the landscape
      was studied for a case area, the oasis of Sangong River in Xinjiang, Northwest
      China where typical arid conditions prevail. Land expansion and contraction among
      various land types and for the entire oasis were analyzed for the periods of 1978
      1987, 1978-1998 and 1987-1998. The changes were closely related to a strong
      economic growth after the land-reform campaign and adoption of the market economy
      in China in the 1980s to early 1990s, a process not strictly Markovian that
      requires stationarity and randomness. Information on land-change status and trend
      is important for a better understanding of the underlying driving processes but
      also for land-use planning and decision-making.

PMID- 17531373
TI  - Short-term in vitro effects of low frequency ultrasound on odontoblast-like
      cells.
AB  - In this study, the effects of low frequency ultrasound (US) were examined on
      odontoblasts, the primary cell responsible for dentinogenesis and dentine repair.
      An established odontoblast-like cell line, MDPC-23, was subjected to 30 kHz
      ultrasound at three different power settings. US induced a marginal level of cell
      death (3% to 4%) at lower amplitudes rising to 25% cell death at the highest
      power tested. The latter was reflected in a 30% decrease in cell attachment after
      4 to 24 h of culture, while the number of adherent cells was reduced by
      approximately 10% to 15% in the lower power groups. Cell replication after 24 h,
      as measured by BrdU incorporation, showed no significant changes in the US
      treated groups. Gene expression analyses demonstrated a moderate dose-dependent
      increase in the expression of GAPDH (glyseraldehyde-3-phosphate dehydrogenase)
      normalised collagen type I, osteopontin (OPN), transforming growth factor-beta1
      (TGFbeta1) and the heat shock protein (hsp) 70. The greatest change was found in
      the expression of the small hsp 25/27, which showed a two- to six-fold increase
      following US treatment. No significant effects were observed for alkaline
      phosphatase (ALP) and core-binding factor A1 (CBFA1/Runx2) expression levels.
      This is the first report describing US effects on odontoblasts. Further studies
      are warranted to elucidate US effects on odontoblast function and to evaluate US
      as a therapeutic application in dentine repair.

PMID- 17531374
TI  - What is the optimal BCG dose in non-muscle-invasive bladder cancer?

PMID- 17531375
TI  - A plea for integrating laparoscopy and robotic surgery in everyday urology: the
      rules of the game.

PMID- 17531376
TI  - Research progress in the use of ferrate(VI) for the environmental remediation.
AB  - The aim of this paper is to review the research progress of using ferrate(VI) in
      following fields of environmental remediation: (1) water disinfection; (2)
      degradation of synthetic organic pollutants; (3) treatment of emerging organic
      pollutants; (4) oxidation of inorganic pollutants; (5) removing humic substance;
      (6) wastewater treatment and disinfection; and (7) sewage sludge treatment.
      Whilst the superior performance of potassium ferrate(VI) as an
      oxidant/disinfectant for the environmental remediation has been demonstrated in
      various recent researches, challenges have existed to the implementation of
      ferrate(VI) technology in full-scale water, wastewater and sewage sludge
      treatment owing to either the instability property of a ferrate(VI) solution or a
      high preparation cost of a solid ferrate(VI). In addition to this, there are some
      fundamental issues which have not yet been studied thoroughly which are crucial
      for the implementation of ferrate(VI)-these lead to the future research work
      recommended by this paper.

PMID- 17531377
TI  - Treatment of 1,10-phenanthroline laboratory wastewater using the solar photo
      Fenton process.
AB  - The red Fe(2+)-phenanthroline complex is the basis of a classical
      spectrophotometric method for determination of iron. Due to the toxicity of this
      complexing agent, direct disposal of the wastewaters generated in analytical
      laboratories is not environmentally safe. This work evaluates the use of the
      solar photo-Fenton process for the treatment of laboratory wastewaters containing
      phenanthroline. Firstly, the degradation of phenanthroline in water was evaluated
      at two concentration levels (0.1 and 0.01%, w/v) and the efficiencies of
      degradation using ferrioxalate (FeOx) and ferric nitrate were compared. The 0.01%
      w/v solution presented much higher mineralization, achieving 82% after 30min of
      solar irradiation with both iron sources. The solar photo-Fenton treatment of
      laboratory wastewater containing, in addition to phenanthroline, other organic
      compounds such as herbicides and 4-chlorophenol, equivalent to 4,500mgL(-1) total
      organic carbon (TOC) resulted in total degradation of phenanthroline and 25% TOC
      removal after 150min, in the presence of either FeOx or ferric nitrate. A ratio
      of 1:10 dilution of the residue increased mineralization in the presence of
      ferrioxalate, achieving 38% TOC removal after 120min, while use of ferric nitrate
      resulted in only 6% mineralization over the same period.

PMID- 17531378
TI  - Sorption of selenium(IV) and selenium(VI) onto natural iron oxides: goethite and
      hematite.
AB  - Selenium is a toxic element with a relatively high mobility in the natural
      waters. Iron oxy-hydroxides might play an important role in the migration of this
      element as well as on its removal from contaminated water. In this work we study
      the interaction of Se(IV), and Se(VI) with natural iron oxides hematite and
      goethite through two series of batch experiments at room temperature. In the
      first series, sorption as a function of initial selenium concentration is studied
      and the results have been fitted with Langmuir isotherms. In a second series of
      experiments, sorption is studied as a function of pH, being the main trend an
      increase of the sorption at acidic pH. The variation of the sorption with pH has
      been modelled with a triple layer surface complexation model and using the FITEQL
      program. The experimental data have been modelled considering for the Se(IV) the
      formation of the FeOSe(O)O(-) complex onto the hematite surface, and a mixture of
      FeOSe(O)O(-), and FeOSe(O)OH onto the goethite surface. For Se(VI) the surface
      complex considered is FeOH(2)(+)-SeO(4)(2-) on both goethite and hematite.

PMID- 17531379
TI  - Possible involvement of supraspinal opioid and GABA receptors in CDP-choline
      induced antinociception in acute pain models in rats.
AB  - Cytidine-5'-diphosphate choline (CDP-choline; citicoline) is an essential
      endogenous compound normally produced by the organism and is a source of cytidine
      and choline. Our recent studies on acute pain models demonstrate that
      intracerebroventricularly administered CDP-choline produces antinociception via
      supraspinal alpha-7 nicotinic acetylcholine receptors-mediated mechanism in rats.
      However, it remains to be elucidated which other supraspinal mechanisms are
      involved in the antinociceptive effect of CDP-choline. In this study, we
      investigated the role of the supraspinal opioidergic, GABAergic, alpha-adrenergic
      and serotonergic receptors in CDP-choline-induced antinociception. The
      antinociceptive effect of CDP-choline was evoked by the intracerebroventricular
      (i.c.v.) administration. Two different pain models were utilized: thermal paw
      withdrawal test and mechanical paw pressure test. The i.c.v. administration of
      CDP-choline (0.5, 1.0 and 2.0 micromol) produced dose-dependent antinociception.
      Non-specific opioid receptor antagonist naloxone (10 microg; i.c.v.) and GABA(B)
      receptor antagonist CGP-35348 (20 microg; i.c.v.) pretreatments inhibited the
      antinociceptive effects of CDP-choline (1.0 micromol; i.c.v.). In contrast, the
      alpha-1 adrenergic receptor antagonist prazosin (20 microg; i.c.v.), alpha-2
      adrenergic receptor antagonist yohimbine (30 microg; i.c.v.) and non-specific
      serotonin receptor antagonist methysergide (20 microg; i.c.v.) pretreatments had
      no effect on CDP-choline-induced antinociception in the thermal paw withdrawal
      test and in the mechanical paw pressure test. Therefore, it can be postulated
      that i.c.v. administered CDP-choline exerts antinociceptive effect mediated by
      supraspinal opioid and GABA(B) receptors in acute pain models. Furthermore,
      supraspinal alpha-adrenergic and serotonergic receptors do not appear to be
      involved in the antinociceptive effect of CDP-choline.

PMID- 17531380
TI  - No association of CETP genotype with cognitive function or age-related cognitive
      change.
AB  - A cholesteryl ester transfer protein (CETP) genotype (V/V homozygosity for I405V,
      NCBI dbSNP rs5882) has been associated with preservation of cognitive function in
      old age, in addition to its associations with exceptional longevity and
      cardiovascular disease. We tested the hypotheses that this polymorphism was
      associated with either level of cognitive function or lifetime cognitive change
      in 525 participants who took part in the Scottish Mental Survey of 1932.
      Participants took the same well-validated mental ability test at ages 11 and 79.
      Scores were also available for several other mental ability tests at age 79, and
      history of cardiovascular disease was available. Frequency of the V/I genotype
      was slightly greater than expected in the sample, possibly consistent with some
      role for the V polymorphism in longevity, and the V/V genotype was associated
      with a lower rate of cardiovascular disease history. There were, however, no
      significant associations of CETP genotype with either childhood IQ or current
      cognitive function in old age, or with lifetime change in cognitive function.

PMID- 17531381
TI  - Association of the hOGG1 Ser326Cys polymorphism with sporadic amyotrophic lateral
      sclerosis.
AB  - Amyotropic lateral sclerosis (ALS) is a fatal and progressive neurodegenerative
      disease causing the loss of motoneurons of the brain and the spinal cord. The
      etiology of ALS is still uncertain, but males are at increased risk for the
      disease than females. Several studies have suggested that motoneurons in ALS
      might be subjected to the double insult of increased DNA oxidative damage and
      deficiencies in DNA repair systems. Particularly, increased levels of 8
      oxoguanine and impairments of the DNA base excision repair system have been
      observed in neurons of ALS patients. There is evidence that the Ser326Cys
      polymorphism of the human 8-oxoguanine DNA glycosylase 1 (hOGG1) gene is
      associated with a reduced DNA repair activity. To evaluate the role of the hOGG1
      Ser326Cys polymorphism in sporadic ALS (sALS), we screened 136 patients and 129
      matched controls. In the total population, we observed association between both
      the Cys326 allele (p=0.02) and the combined Ser326Cys+Cys326Cys genotype
      (OR=1.65, 95% CI=1.06-2.88) and increased risk of disease. After stratification
      by gender, the Cys326 allele (p=0.01), both the Ser326Cys genotype (OR=2.14, 95%
      CI=1.09-4.19) and the combined Ser326Cys+Cys326Cys genotype (OR=2.15, 95% CI=1.16
      4.01) were associated with sALS risk only in males. No significant association
      between the Ser326Cys polymorphism and disease phenotype, including age and site
      of onset and disease progression, was observed. Present results suggest a
      possible involvement of the hOGG1 Ser326Cys polymorphism in sALS pathogenesis.

PMID- 17531382
TI  - Enhanced activity of GABA receptors inhibits glutamate release induced by focal
      cerebral ischemia in rat striatum.
AB  - Cerebral ischemia causes an excess release of glutamate, which can injure
      neurons. The striatum is one of the important regions vulnerable to hypoxia and
      ischemia. Using push-pull perfusion technique, we investigated the regulatory
      role of gamma-aminobutyric acid (GABA) and its receptors in modifying the amount
      of glutamate in rat striatum with ischemia. Perfusion with exogenous GABA (1 mM)
      inhibited cerebral ischemia-induced glutamate release by as much as 47%. We
      further characterized relative roles of subtype receptors of GABA on glutamate
      release by using pharmacological tools. While baclofen (500 microM), a GABA(B)
      receptor agonist, suppressed ischemia-induced glutamate release by 52%, GABA(B)
      receptor antagonist saclofen (500 microM) failed to produce a significant
      increase of glutamate release. The GABA(A) receptor agonist muscimol (500 microM)
      also reduced by 38% the release of glutamate induced by cerebral ischemia but the
      GABA(A) receptor antagonist bicuculline (500 microM) had very little effect. The
      present study demonstrates that the excessive release of glutamate or the overly
      activated glutamate receptor, triggered by cerebral ischemia, can be down
      regulated by exogenous GABA or by increased activity of GABA receptors,
      especially the presynaptic GABA(B) receptors, which might be one of the important
      mechanisms to protect against striatum neuronal damage from over stimulation by
      excessive glutamate during ischemia.

PMID- 17531383
TI  - Japanese encephalitis virus infection decrease endogenous IL-10 production:
      correlation with microglial activation and neuronal death.
AB  - The anti-inflammatory cytokine interleukin (IL)-10 is synthesized in the central
      nervous system (CNS) and acts to limit clinical symptoms of stroke, multiple
      sclerosis, Alzheimer's disease, meningitis, and the behavioral changes that occur
      during bacterial infections. Expression of IL-10 is critical during the course of
      most major diseases in the CNS and promotes survival of neurons and all glial
      cells in the brain by blocking the effects of proinflammatory cytokines and by
      promoting expression of cell survival signals. In order to assess functional
      importance of this cytokine in viral encephalitis we have exploited an
      experimental model of Japanese encephalitis (JE). We report for the first time
      that in Japanese encephalitis, there is a progressive decline in level of IL-10.
      The extent of progressive decrease in IL-10 level following viral infection is
      inversely proportional to the increase in the level of proinflammatory cytokines
      as well as negative consequences that follows viral infection.

PMID- 17531384
TI  - Galectin-3 expression is correlated with abnormal prion protein accumulation in
      murine scrapie.
AB  - To investigate the involvement of galectin-3 in the process of neurodegeneration
      in prion diseases, the expression and cellular localization of galectin-3 in the
      brain were studied in scrapie, a mouse model of prion disease. Reverse
      transcription-polymerase chain reaction (RT-PCR) and Western blot analyses showed
      that the expression of galectin-3 protein and mRNA was induced in scrapie
      affected brains, particularly at the time when the abnormal prion protein PrP(Sc)
      began to accumulate in the brains. Immunohistochemically, immunostaining for
      galectin-3 was found mainly in B4-isolectin-positive cells (presumably activated
      microglia/macrophages), but not in astrocytes. Galectin-3 immunoreactivity was
      localized mainly in areas of PrP(Sc) accumulation and neuronal death in scrapie
      infected brains. These findings suggest that the expression of galectin-3 by
      activated microglia/macrophages in prion disease correlates with abnormal prion
      protein accumulation.

PMID- 17531385
TI  - Neuroprotective effects of resveratrol against traumatic brain injury in immature
      rats.
AB  - Childhood trauma resulting in traumatic brain injury (TBI) due to accidents and
      abuse is the major cause of death and dysfunction in the young. Since there are
      no approved specific pharmacological agents that block the progression of the
      secondary injury, the current management of TBI is mainly supportive. We aimed to
      determine the effect of resveratrol on hippocampal damage and behavioral deficits
      in 7-day-old rat pups subjected to contusion injury. Resveratrol was injected
      intraperitoneally at the doses of 100 mg/kg of body weight immediately after
      induction of traumatic injury. Hippocampal damage was examined by cresyl violet
      staining and behavioral alterations were evaluated using open field and novel
      object recognition tests 2 weeks after trauma. Histopathological evaluation
      showed that treatment with a single dose of 100 mg/kg resveratrol (i.p.) after
      the trauma significantly ameliorated the trauma induced hippocampal neuron loss
      at ipsilateral and contralateral hippocampal brain regions of rats. Additionally,
      treatment with resveratrol decreased anxiety and increased cortex/hippocampus
      dependent memory of animals subjected to blunt head trauma. These results show
      that acute treatment of resveratrol has a neuroprotective role against trauma
      induced hippocampal neuron loss and associated cognitive impairment in rats.

PMID- 17531386
TI  - 3,4-dihydroxybenzoic acid from Smilacis chinae rhizome protects amyloid beta
      protein (25-35)-induced neurotoxicity in cultured rat cortical neurons.
AB  - The neuroprotective effect of 3,4-dihydroxybenzoic acid (3,4-DHBA) isolated from
      Smilacis chinae rhizome against Abeta (25-35)-induced neurotoxicity on cultured
      rat cortical neurons was found in this study. The protective effect of 3,4-DHBA
      against Abeta (25-35)-induced neuronal cell death was investigated by measuring
      cell viability via a 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium
      bromide (MTT) assay and Hoechst 33342 staining. 3,4-DHBA (1 and 10 microM)
      concentration-dependently inhibited 10 microM Abeta (25-35)-induced neuronal
      apoptotic death. 3,4-DHBA (1 and 10 microM) inhibited 10 microM Abeta (25-35)
      induced elevation of cytosolic Ca(2+) concentration ([Ca(2+)](c)), which was
      measured by a fluorescent dye, Fluo-4 AM. 3,4-DHBA also inhibited glutamate
      release into medium, reactive oxygen species (ROS) generation, and caspase-3
      activation, which were induced by 10 microM Abeta (25-35). These results suggest
      that 3,4-DHBA prevents Abeta (25-35)-induced neuronal cell damage by interfering
      with the increase of [Ca(2+)](c), and then by inhibiting glutamate release,
      generation of ROS and caspase-3 activity.

PMID- 17531387
TI  - Bitter taste and blood glucose are not involved in the suppressive effect of
      dietary histidine on food intake.
AB  - Histamine decreases food intake by activating histaminergic neurons in the
      hypothalamus. Histamine is synthesized by histidine decarboxylase (HDC) from
      histidine. The purpose of this three-part animal study was to clarify the
      mechanism underlying the suppressive effect of dietary histidine on food intake.
      In experiment 1, we attempted to distinguish palatability from a direct effect of
      dietary histidine because histidine tastes slightly bitter to humans. We measured
      food intake every hour for 24 h in rats fed with a histidine-enriched diet or one
      of various quinine diets (0.001-0.8% quinine), also bitter. In experiment 2, we
      measured changes in blood glucose levels in rats fed with a standard or histidine
      enriched diet because blood glucose is known to decrease food intake. In
      experiment 3, we intraperitoneally injected fluoromethylhistidine (FMH), an
      antagonistic inhibitor of HDC, in rats fed with a histidine-enriched diet. In
      experiment 1, food intake was almost the same in rats fed with the histidine
      enriched diet as that in rats fed with the 0.01% quinine diet until 6 h, but food
      intake was low in other groups compared with that in the histidine-enriched diet
      group. After 6 h, food intake did not increase in rats fed with the histidine
      enriched diet. In experiment 2, the blood glucose level rose quickly and then
      began to decrease at approximately 2 h in both groups of rats. However, it
      decreased more dramatically in rats fed with the histamine-enriched diet and
      reaches a significant difference from the decrease in the standard-diet group by
      6 h. In experiment 3, food intake increased significantly in FMH-injected rats
      fed with the histidine-enriched diet compared with in non-FMH injected rats. Our
      results suggest that dietary histidine suppresses food intake by activating
      histaminergic neurons in the hypothalamus, independently bitter taste and blood
      glucose level.

PMID- 17531388
TI  - Applying the fear-avoidance model to the chronic whiplash syndrome.

PMID- 17531389
TI  - Deletion of the acid-sensing ion channel ASIC3 prevents gastritis-induced acid
      hyperresponsiveness of the stomach-brainstem axis.
AB  - Gastric acid challenge of the rat and mouse stomach is signalled to the brainstem
      as revealed by expression of c-Fos. The molecular sensors relevant to the
      detection of gastric mucosal acidosis are not known. Since the acid-sensing ion
      channels ASIC2 and ASIC3 are expressed by primary afferent neurons, we examined
      whether knockout of the ASIC2 or ASIC3 gene modifies afferent signalling of a
      gastric acid insult in the normal and inflamed stomach. The stomach of conscious
      mice (C57BL/6) was challenged with intragastric HCl; two hours later the
      activation of neurons in the nucleus tractus solitarii (NTS) of the brainstem was
      visualized by c-Fos immunocytochemistry. Mild gastritis was induced by addition
      of iodoacetamide (0.1%) to the drinking water for 7 days. Exposure of the gastric
      mucosa to HCl (0.25M) caused a 3-fold increase in the number of c-Fos-positive
      neurons in the NTS. This afferent input to the NTS remained unchanged by ASIC3
      knockout, whereas ASIC2 knockout augmented the c-Fos response to gastric HCl
      challenge by 33% (P<0.01). Pretreatment of wild-type mice with iodoacetamide
      induced mild gastritis, as revealed by increased myeloperoxidase activity, and
      enhanced the number of NTS neurons responding to gastric HCl challenge by 41%
      (P<0.01). This gastric acid hyperresponsiveness was absent in ASIC3 knockout mice
      but fully preserved in ASIC2 knockout mice. The current data indicate that ASIC3
      plays a major role in the acid hyperresponsiveness associated with experimental
      gastritis. In contrast, ASIC2 appears to dampen acid-evoked input from the
      stomach to the NTS.

PMID- 17531390
TI  - Haemonchosis and teladorsagiosis in a Scottish sheep flock putatively associated
      with the overwintering of hypobiotic fourth stage larvae.
AB  - The cause of ill thrift and deaths was investigated in a group of 40 Scottish
      lowground ewes, which had been treated with levamisole and then turned onto clean
      grazing after lambing, 6-8 weeks previously. Concurrent haemonchosis and
      teladorsagiosis were diagnosed, putatively associated with the spring maturation
      of large numbers of hypobiotic larvae. Ill thrift due to parasitic
      gastroenteritis consequently occurred in the lambs which had been turned onto the
      'clean' grazing with their dams, despite metaphylactic anthelmintic treatments.
      The contributory role of haemonchosis resulting in serious production-limiting
      disease is unusual in Scottish sheep flocks. It is suggested that the problem may
      have arisen as a consequence of the adaptation of Haemonchus contortus to survive
      overwinter in a cold climate as arrested early fourth stage larvae, which were
      not eliminated when the ewes were treated with levamisole at turnout.

PMID- 17531391
TI  - At least two genetically distinct large Babesia species infective to sheep and
      goats in China.
AB  - A fatal disease of sheep and goats in the northern part of China has been
      reported to be due to Babesia ovis. However, some characteristics of the
      causative agent in recent reports are not in accordance with the original
      attributes ascribed to this parasite. Therefore, the 18S small subunit ribosomal
      RNA (18S rRNA) genes of a number of Babesia isolates in China were sequenced and
      compared with that of other Babesia and Theileria species in an attempt to
      clarify their taxonomic position. In the present study, seven Babesia isolates
      were collected from distinct areas of northern China, and the 18S rRNA genes were
      amplified and sequenced. The phylogenetic trees were inferred based on 18S rRNA
      gene sequences of the Chinese ovine Babesia isolates and some of ovine Babesia
      and Theileria species available in GenBank. In the phylogenetic tree, Babesia sp.
      isolates from Madang, Tianzhu, Lintan, Ningxian, Hebei and Liaoning all grouped
      with B. motasi with 88.2-99.9% identity, while Babesia sp. Xinjiang grouped in a
      separate clade between B. ovis and B. crassa with 79.7-81.2% identity. The
      results indicated that there are at least two distinct Babesia species groups-B.
      motasi and Babesia sp. Xinjiang, the latter was distinctly different from other
      ovine Babesia isolates from China with less than 86.6% identity.

PMID- 17531392
TI  - Burns due to flaming alcoholic beverages in the UK: a mini series and
      experimental study.

PMID- 17531393
TI  - The descriptive epidemiology of intentional burns in the United States: an
      analysis of the National Burn Repository.
AB  - BACKGROUND: Epidemiologic research on intentional burns in the United States has
      mainly been based on small, geographically restricted populations. The current
      study presents the descriptive epidemiology of intentional burns using data from
      a large, geographically diverse population of burn patients. METHODS: The
      National Burn Repository (NBR) was queried for patients with intentional burns
      and analyzed data pertaining to their demographic and medical characteristics;
      primarily comparing the prevalence proportions of these variables according to
      specific injury intent. RESULTS: From a total of 54,219 burn patients, 1601
      patients who sustained intentional burns were identified; 49% were self
      inflicted, and 51% were assault-related. Compared to all other burn patients,
      intentional burn patients had a larger mean total body surface area (TBSA) burned
      (22.0% versus 11.3%, p<0.0001), longer hospital stay (19.8 days versus 12.5 days,
      p<0.0001), and higher mortality (13.9% versus 2.5%, p<0.0001). Self-inflicted
      compared to assault-related burns were associated with a larger TBSA burned
      (27.5% versus 16.8%, p<0.0001) and higher mortality (20.8% versus 7.2%,
      p<0.0001). CONCLUSIONS: Data from this national cohort of burn patients support
      findings from smaller studies that patients who suffer intentional burns
      experience excess morbidity and mortality.

PMID- 17531394
TI  - Influence of sex and estrous cycle on the effects of acute tryptophan depletion
      induced by a gelatin-based mixture in adult Wistar rats.
AB  - Women are more vulnerable to develop depression and anxiety disorders than men.
      This may be related to higher serotonergic vulnerability in women. Serotonergic
      vulnerability entails that differences between people in the regulation of
      serotonin (5-HT) determine the vulnerability of an individual to develop
      depression or other 5-HT-related disorders. The aim of the present experiment was
      to evaluate whether male and female Wistar rats differ in serotonergic
      vulnerability. Here, a stronger behavioral response to acute tryptophan (TRP)
      depletion was assumed to reflect serotonergic vulnerability. Twenty-four male and
      48 female rats were repeatedly subjected to treatment with a gelatin-based
      protein-carbohydrate mixture, either with or without L-tryptophan. Female estrous
      cycle phase was determined by means of vaginal smears and the females were
      divided into two groups based on their estrous cycle phase: pro-estrus/estrus and
      met-estrus/di-estrus. Blood samples showed stronger TRP depletion in males than
      females. There was no effect of estrous cycle on plasma TRP concentrations. In
      contrast, treatment effects on some brain TRP concentrations were influenced by
      estrous cycle phase, females in pro-estrus/estrus showed the strongest response
      to TRP depletion. In the open field test and home cage emergence test, females in
      pro-estrus/estrus also showed the strongest behavioral response to acute TRP
      depletion. In general, females showed more activity than males in anxiety-related
      situations and this effect appeared to be enhanced by TRP depletion. In the
      social interaction test, passive body contact in males and females in pro
      estrus/estrus was decreased after TRP depletion whereas it was increased in
      females in the met-estrus/di-estrus phase. Acute TRP depletion affected object
      recognition, but did not affect behavior in the forced swimming test and a
      reaction time task. It is concluded that sex and estrous cycle phase can
      influence the behavioral response to TRP depletion, and that females in pro
      estrus/estrus show the strongest behavioral response to acute TRP depletion.

PMID- 17531395
TI  - Decreased heat tolerance is associated with hypothalamo-pituitary-adrenocortical
      axis impairment.
AB  - When rats are exposed to heat, they adapt themselves to the stressor with a wide
      inter-individual variability. Such differences in heat tolerance may be related
      to particularities in the hypothalamo-pituitary-adrenocortical (HPA) axis
      activation. To further this hypothesis, 80 rats instrumented with a telemetric
      device for abdominal temperature (Tabd) measurement were separated into two
      groups. Sixty-eight rats were exposed during 90 min at an ambient temperature of
      40 degrees C, and 12 rats to an ambient temperature of 22 degrees C. Heat-exposed
      rats were then divided into three groups using the a posteriori k-means
      clustering method according to their Tabd level at the end of heat exposure. Heat
      tolerant rats (Tol, n=30) exhibiting the lowest Tabd showed a slight dehydration,
      a moderate triglyceride mobilization, but the highest plasma adrenocorticotropic
      hormone (ACTH) and corticosterone levels. Conversely, heat exhausted rats (HE,
      n=14) presented the highest Tabd, a higher degree of dehydration, a greater
      metabolic imbalance with the lowest plasma triglyceride level and the highest
      lactate concentration, as well as a lowest plasma corticosterone and ACTH levels.
      The fact that the proopiomelanocortin (POMC) mRNA content within the pituitary
      was low despite of a high c-fos mRNA level is also relevant. Current inflammatory
      processes in HE rats were underlined by lower inhibitory factor kappaBalpha
      (IkappaBalpha) mRNA and higher tumor necrosis factor-alpha (TNF-alpha) and
      interleukin-1beta (IL-1beta) mRNA. In conclusion, data show that intolerance to
      heat exposure is associated to an HPA axis impairment, possibly related to
      changes occurring in the IkappaBalpha and TNF-alpha mRNA levels.

PMID- 17531396
TI  - Melancholic major depression and epilepsy.
AB  - An analysis is carried out of a set of psychic phenomena appearing always in the
      same way: an experience suddenly invades the consciousness, unfolding
      automatically and with great intensity. This psychic automatism, of which the
      patient is a passive observer, is accompanied by an overwhelming feeling of
      strangeness. Our hypothesis is that these phenomena are the expression of partial
      seizures with a psychic content, and the name Paroxysmal Psychic Automatisms is
      proposed for all of them. A comparative study is then made of the phenomenology
      of partial seizures with a psychic content, on the one hand, and of that of
      melancholic major depression, on the other. It reveals a wealth of clinical
      information indicating an overlap between the two conditions. Finally, a set of
      well-established scientific data is analysed concerning epilepsy and depression,
      especially epidemiological and psychopharmacological information, which takes on
      a new meaning in the light of the hypothesis developed in this paper.

PMID- 17531397
TI  - The different volume effects of small-bowel toxicity during pelvic irradiation
      between gynecologic patients with and without abdominal surgery: a prospective
      study with computed tomography-based dosimetry.
AB  - PURPOSE: To evaluate the effect of abdominal surgery on the volume effects of
      small-bowel toxicity during whole-pelvic irradiation in patients with gynecologic
      malignancies. METHODS AND MATERIALS: From May 2003 through November 2006, 80
      gynecologic patients without (Group I) or with (Group II) prior abdominal surgery
      were analyzed. We used a computed tomography (CT) planning system to measure the
      small-bowel volume and dosimetry. We acquired the range of small-bowel volume in
      10% (V10) to 100% (V100) of dose, at 10% intervals. The onset and grade of
      diarrhea during whole-pelvic irradiation were recorded as small-bowel toxicity up
      to 39.6 Gy in 22 fractions. RESULTS: The volume effect of Grade 2-3 diarrhea
      existed from V10 to V100 in Group I patients and from V60 to V100 in Group II
      patients on univariate analyses. The V40 of Group I and the V100 of Group II
      achieved most statistical significance. The mean V40 was 281 +/- 27 cm(3) and 489
      +/- 34 cm(3) (p < 0.001) in Group I patients with Grade 0-1 and Grade 2-3
      diarrhea, respectively. The corresponding mean V100 of Group II patients was 56
      +/- 14 cm(3) and 132 +/- 19 cm(3) (p = 0.003). Multivariate analyses revealed
      that V40 (p = 0.001) and V100 (p = 0.027) were independent factors for the
      development of Grade 2-3 diarrhea in Groups I and II, respectively. CONCLUSIONS:
      Gynecologic patients without and with abdominal surgery have different volume
      effects on small-bowel toxicity during whole-pelvic irradiation. Low-dose volume
      can be used as a predictive index of Grade 2 or greater diarrhea in patients
      without abdominal surgery. Full-dose volume is more important than low-dose
      volume for Grade 2 or greater diarrhea in patients with abdominal surgery.

PMID- 17531398
TI  - Prevention of radiochemotherapy-induced esophagitis with glutamine: results of a
      pilot study.
AB  - PURPOSE: To assess the usefulness of oral glutamine to prevent radiochemotherapy
      induced esophagitis in patients with lung cancer, and to determine the dosimetric
      parameter predictive of esophagitis. METHODS AND MATERIALS: Seventy-five patients
      were enrolled; 34.7% received sequential radiochemotherapy, and 65.3% received
      concomitant radiochemotherapy. Every patient received prophylactic glutamine
      powder in doses of 10 g/8 h. Prescribed radiation doses were 45-50 Gy to planning
      target volume (PTV)1 (gross tumor volume plus wide margins) and 65-70 Gy to PTV2
      (reduced margins). The primary endpoint was the incidence of Grade 2 or greater
      acute esophagitis. RESULTS: No patient experienced glutamine intolerance or
      glutamine-related toxicity. Seventy-three percent of patients who received
      sequential chemotherapy and 49% of those who received concomitant chemotherapy
      did not present any form of esophagitis. V50 was the dosimetric parameter with
      better correlation between esophagitis and its duration. A V50 of <or=30% had a
      22% risk of esophagitis Grade >or=2, which increased to 71% with a V50 of >30% (p
      = 0.0009). CONCLUSIONS: The use of oral glutamine may have an important role in
      the prevention of esophageal complications of concomitant radiochemotherapy in
      lung cancer patients. However, randomized trials are needed to corroborate that
      effect. V50 is the dosimetric parameter with better correlation with esophagitis
      grade and duration.

PMID- 17531399
TI  - Setup variations in radiotherapy of esophageal cancer: evaluation by daily
      megavoltage computed tomographic localization.
AB  - PURPOSE: To use pretreatment megavoltage computed tomography (MVCT) scans to
      evaluate setup variations in anterior-posterior (AP), lateral, and superior
      inferior (SI) directions and rotational variations, including pitch, roll, and
      yaw, for esophageal cancer patients treated with helical tomotherapy. METHODS AND
      MATERIALS: Ten patients with locally advanced esophageal cancer treated by
      combined chemoradiation using helical tomotherapy were selected. After patients
      were positioned using their skin tattoos/marks, MVCT scans were performed before
      every treatment and automatically registered to planning kilovoltage CT scans
      according to bony landmarks. Image registration data were used to adjust patient
      setups before treatment. A total of 250 MVCT scans were analyzed. Correlations
      between setup variations and body habitus, including height, weight, relative
      weight change, body surface area, and patient age, were evaluated. RESULTS: The
      standard deviations for systematic setup corrections in AP, lateral, and SI
      directions and pitch, roll, and yaw rotations were 1.5, 3.7, and 4.8 mm and 0.5
      degrees, 1.2 degrees, and 0.8 degrees, respectively. The appropriate averages of
      random setup variations in AP, lateral, and SI directions and pitch, roll, and
      yaw rotations were 2.9, 5.2, and 4.4 mm, and 1.0 degrees, 1.2 degrees, and 1.1
      degrees, respectively. Setup variations were stable throughout the entire course
      of radiotherapy in all three translational and three rotational displacements,
      with little change in magnitude. No significant correlations were found between
      setup variations and body habitus variables. CONCLUSIONS: Daily MVCT scans before
      each treatment can effectively detect setup errors and thereby reduce planning
      target volume (PTV) margins. This will reduce radiation dose to critical organs
      and may translate into lower treatment-related toxicities.

PMID- 17531400
TI  - Breast-conserving treatment with partial or whole breast irradiation for low-risk
      invasive breast carcinoma--5-year results of a randomized trial.
AB  - PURPOSE: To report the 5-year results of a randomized study comparing the
      survival and cosmetic results of breast-conserving treatment with partial breast
      irradiation (PBI) or conventional whole breast irradiation (WBI). METHODS AND
      MATERIALS: Between 1998 and 2004, 258 selected patients with T1 N0-1mi, Grade 1
      2, nonlobular breast cancer without presence of extensive intraductal component
      and resected with negative margins were randomized after breast-conserving
      surgery to receive 50 Gy/25 fractions WBI (n = 130) or PBI (n = 128). The latter
      consisted of either 7 x 5.2 Gy high-dose-rate (HDR) multicatheter brachytherapy
      (BT; n = 88) or 50 Gy/25 fractions electron beam (EB) irradiation (n = 40).
      RESULTS: At a median follow-up of 66 months, the 5-year actuarial rate of local
      recurrence was 4.7% and 3.4% in the PBI and WBI arms, respectively (p = 0.50).
      There was no significant difference in the 5-year probability of overall survival
      (94.6% vs. 91.8%), cancer-specific survival (98.3% vs. 96.0%), and disease-free
      survival (88.3% vs. 90.3%). The rate of excellent to good cosmetic result was
      77.6% in the PBI group (81.2% after HDR BT; 70.0% after EB) and 62.9% in the
      control group (52.2% after telecobalt; 65.6% after 6-9-MV photons; p(WBI/PBI) =
      0.009). CONCLUSIONS: Partial breast irradiation using interstitial HDR implants
      or EB to deliver radiation to the tumor bed alone for a selected group of early
      stage breast cancer patients produces 5-year results similar to those achieved
      with conventional WBI. Significantly better cosmetic outcome can be achieved with
      carefully designed HDR multicatheter implants compared with the outcome after
      WBI.

PMID- 17531401
TI  - An update of the phase III trial comparing whole pelvic to prostate only
      radiotherapy and neoadjuvant to adjuvant total androgen suppression: updated
      analysis of RTOG 94-13, with emphasis on unexpected hormone/radiation
      interactions.
AB  - PURPOSE: This trial was designed to test the hypothesis that total androgen
      suppression and whole pelvic radiotherapy (WPRT) followed by a prostate boost
      improves progression-free survival (PFS) by > or =10% compared with total
      androgen suppression and prostate only RT (PORT). This trial was also designed to
      test the hypothesis that neoadjuvant hormonal therapy (NHT) followed by
      concurrent total androgen suppression and RT improves PFS compared with RT
      followed by adjuvant hormonal therapy (AHT) by > or =10%. METHODS AND MATERIALS:
      Patients eligible for the study included those with clinically localized
      adenocarcinoma of the prostate and an elevated prostate-specific antigen level of
      <100 ng/mL. Patients were stratified by T stage, prostate-specific antigen level,
      and Gleason score and were required to have an estimated risk of lymph node
      involvement of >15%. RESULTS: The difference in overall survival for the four
      arms was statistically significant (p = 0.027). However, no statistically
      significant differences were found in PFS or overall survival between NHT vs. AHT
      and WPRT compared with PORT. A trend towards a difference was found in PFS (p =
      0.065) in favor of the WPRT + NHT arm compared with the PORT + NHT and WPRT + AHT
      arms. CONCLUSIONS: Unexpected interactions appear to exist between the timing of
      hormonal therapy and radiation field size for this patient population. Four Phase
      III trials have demonstrated better outcomes when NHT was combined with RT
      compared with RT alone. The Radiation Therapy Oncology Group 9413 trial results
      have demonstrated that when NHT is used in conjunction with RT, WPRT yields a
      better PFS than does PORT. It also showed that when NHT + WPRT results in better
      overall survival than does WPRT + short-term AHT. Additional studies are
      warranted to determine whether the failure to demonstrate an advantage for NHT +
      WPRT compared with PORT + AHT is chance or, more likely, reflects a previously
      unrecognized biologic phenomenon.

PMID- 17531403
TI  - Regulation of the promoter of CUG triplet repeat binding protein, Cugbp1, during
      myogenesis.
AB  - CUG triplet repeat binding protein, CUGBP1, plays a critical role in the
      development of skeletal muscle pathology in patients with Myotonic Dystrophy 1
      (DM1). In this paper, we have characterized transcriptional regulation of mouse
      Cugbp1 gene during normal myogenesis. There are several Cugbp1 mRNA species with
      variable 5' ends. We found that these mRNA species have different patterns of
      expression during myogenesis. Isoforms 1 and 2 are mainly expressed in myotubes,
      while expression of isoform 3 is increased during transition of myoblasts to
      myotubes and during transition of myotubes to myofibers. We have cloned a short
      region of the Cugbp1 promoter, which is responsible for the regulation of the
      isoform 3, and have identified within this region three different transcription
      start sites. This promoter region exhibits high activity in myoblasts and the
      activity of this region is significantly increased in myotubes. The Cugbp1
      promoter contains three E-box elements. A mutation of one of the E-boxes, E(3),
      significantly reduces activity of the Cugbp1 promoter. Gelshift and ChIP assays
      showed that E(3)-box is occupied by E12, CBP and p300 proteins in myoblasts,
      while in differentiated myotubes this element is occupied by myogenin, E12 and
      p300. The binding of myogenin to the Cugbp1 promoter correlates with activation
      of the promoter during differentiation. Our data show that myogenin is a key
      regulator of the Cugbp1 promoter since overexpression of myogenin increases the
      activity of the Cugbp1 promoter; while the inhibition of myogenin reduces
      activity of the Cugbp1 promoter. These data show that transcription of Cugbp1
      gene in muscle is regulated by myogenin and E proteins and suggest that the co
      operation of several transcription factors is important for the activation of the
      Cugbp1 promoter.

PMID- 17531404
TI  - Exploiting a list of protein sequences.
AB  - We describe a software program to help exploit a database of aligned protein
      sequences. In addition to the classical lists of sequences, a graphical
      representation is used to get a better overview of the information. As natural
      parameters, the type of amino acid and sequence position are used. Various plots
      or 3D representations are then updated. Examples are shown based on globin
      sequences from various species and on the abnormal human hemoglobins. The
      software should be of interest to protein engineers who need to know what
      variants are already known.

PMID- 17531406
TI  - Transient ligand docking sites in Cerebratulus lacteus mini-hemoglobin.
AB  - The monomeric hemoglobin of the nemertean worm Cerebratulus lacteus functions as
      an oxygen storage protein to maintain neural activity under hypoxic conditions.
      It shares a large, apolar matrix tunnel with other small hemoglobins, which has
      been implicated as a potential ligand migration pathway. Here we explore ligand
      migration and binding within the distal heme pocket, to which the tunnel provides
      access to ligands from the outside. FTIR/TDS experiments performed at cryogenic
      temperatures reveal the presence of three transient ligand docking sites within
      the distal pocket, the primary docking site B on top of pyrrole C and secondary
      sites C and D. Site C is assigned to a cavity adjacent to the distal portion of
      the heme pocket, surrounded by the B and E helices. It has an opening to the
      apolar tunnel and is expected to be on the pathway for ligand entry and exit,
      whereas site D, circumscribed by TyrB10, GlnE7, and the CD corner, most likely is
      located on a side pathway of ligand migration. Flash photolysis experiments at
      ambient temperatures indicate that the rate-limiting step for ligand binding to
      CerHb is migration through the apolar channel to site C. Movement from C to B and
      iron-ligand bond formation involve low energy barriers and thus are very rapid
      processes in the wt protein.

PMID- 17531407
TI  - Characterization of a multifunctional inositol phosphate kinase from rice and
      barley belonging to the ATP-grasp superfamily.
AB  - OsIpk and HvIpk, inositol phosphate kinases, were cloned from rice (Oryza sativa
      L. var. indica, IR64) and barley (Hordeum vulgare) respectively. Sequence
      alignment showed that they belong to the ATP-grasp family, which includes
      inositol 1,3,4-trisphosphate 5/6-kinase from humans and Arabidopsis. Residues
      that are binding sites for ATP and coordinate magnesium in absence or presence of
      inositol phosphate are conserved and in total 23 residues are invariant among the
      twelve aligned inositol phosphate kinases. The genes were heterologously
      expressed in Escherichia coli and kinase activity assays with 17 different
      isomers of inositol mono-/di-/tri-/tetra-/pentaphosphate as well as phytate were
      performed. The strongest activity for both kinases was observed with
      Ins(3,4,5,6)P(4), which candidates as the primary substrate for these kinases in
      plants. Several species-specific differences between the two recombinant Ipks
      were observed. Rice OsIpk showed detectable kinase activity towards eight
      different substrates, whereas barley HvIpk showed kinase activity with all the
      substrates including inositol mono- and bisphosphates. HvIpk showed 3-kinase
      activity towards the Ins(1,4,5)P(3) substrate and it also interconverted the two
      substrates Ins(1,3,4,5)P(4) and Ins(1,3,4,6)P(4) by isomerase activity, which was
      not observed for the rice homologue. Both OsIpk and HvIpk had no detectable 2
      kinase activity. Furthermore, the two Ipks showed phosphatase activity towards
      several inositol phosphates. Expression analysis by RT-PCR demonstrated that the
      Ipk gene was equally expressed in different tissues and developmental stages.
      Taken together, these results show that the Ipk kinase plays a significant role
      in the inositol phosphate interacting network in plants.

PMID- 17531405
TI  - Formation of the 3' end of histone mRNA: getting closer to the end.
AB  - Nearly all eukaryotic mRNAs end with a poly(A) tail that is added to their 3' end
      by the ubiquitous cleavage/polyadenylation machinery. The only known exceptions
      to this rule are metazoan replication-dependent histone mRNAs, which end with a
      highly conserved stem-loop structure. This distinct 3' end is generated by
      specialized 3' end processing machinery that cleaves histone pre-mRNAs 4-5
      nucleotides downstream of the stem-loop and consists of the U7 small nuclear RNP
      (snRNP) and number of protein factors. Recently, the U7 snRNP has been shown to
      contain a unique Sm core that differs from that of the spliceosomal snRNPs, and
      an essential heat labile processing factor has been identified as symplekin. In
      addition, cross-linking studies have pinpointed CPSF-73 as the endonuclease,
      which catalyzes the cleavage reaction. Thus, many of the critical components of
      the 3' end processing machinery are now identified. Strikingly, this machinery is
      not as unique as initially thought but contains at least two factors involved in
      cleavage/polyadenylation, suggesting that the two mechanisms have a common
      evolutionary origin. The greatest challenge that lies ahead is to determine how
      all these factors interact with each other to form a catalytically competent
      processing complex capable of cleaving histone pre-mRNAs.

PMID- 17531408
TI  - First detection of canine parvovirus type 2c in South America.
AB  - Since its sudden emergence in the early 1970s, canine parvovirus type-2 (CPV-2)
      has been evolving through the generation of novel genetic and antigenic variants
      (CPV-2a/b/c and a number of additional mutations) that are unevenly distributed
      throughout the world. In order to develop strategies to control the spread of
      these variants and to understand virus evolution is fundamental to genotype field
      isolates from different geographic locations. In the present paper we have
      examined 25 isolates of CPV from clinical samples of Uruguayan dogs collected
      during year 2006. A fragment of the VP2 gene of the virus was analyzed using
      polymerase chain reaction (PCR), restriction fragment length polymorphism (RFLP)
      and DNA sequence analysis. Out of the 25 isolates analyzed, only one was
      characterized as CPV-2a and 24 were characterized as CPV-2c, indicating that this
      type is currently the prevalent field CPV circulating in Uruguay. This is the
      first report of CPV-2c in the American continent and it also represents the
      highest frequency of this type observed in a dog population so far. Its presence
      in South American supports the assumption that CPV-2c is reaching a worldwide
      distribution as occurred with 2a/2b antigenic types.

PMID- 17531409
TI  - Real-time PCR for detection and differentiation of Streptococcus equi subsp. equi
      and Streptococcus equi subsp. zooepidemicus.
AB  - Strangles is a contagious equine disease caused by Streptococcus equi subsp.
      equi. In this study, clinical strains of S. equi (n=24) and Streptococcus equi
      subsp. zooepidemicus (n=24) were genetically characterized by sequencing of the
      16S rRNA and sodA genes in order to devise a real-time PCR system that can detect
      S. equi and S. zooepidemicus and distinguish between them. Sequencing
      demonstrated that all S. equi strains had the same 16S rRNA sequence, whereas S.
      zooepidemicus strains could be divided into subgroups. One of these (n=12
      strains) had 16S rRNA sequences almost identical with the S. equi strains.
      Interestingly, four of the strains biochemically identified as S. zooepidemicus
      were found by sequencing of the 16S rRNA gene to have a sequence homologous with
      Streptococcus equi subsp. ruminatorum. However, they did not have the colony
      appearance or the biochemical characteristics of the type strain of S.
      ruminatorum. Classification of S. ruminatorum may thus not be determined solely
      by 16S rRNA sequencing. Sequencing of the sodA gene demonstrated that all S. equi
      strains had an identical sequence. For the S. zooepidemicus strains minor
      differences were found between the sodA sequences. The developed real-time PCR,
      based on the sodA and seeI genes was compared with conventional culturing on 103
      cultured samples from horses with suspected strangles or other upper respiratory
      disease. The real-time PCR system was found to be more sensitive than
      conventional cultivation as two additional field isolates of S. equi and four of
      S. zooepidemicus were detected.

PMID- 17531410
TI  - Premenopausal factors influencing premature ovarian failure and early menopause.
AB  - OBJECTIVES: We conducted this study to examine premenopausal risk factors
      associated with premature ovarian failure (POF) and early menopause (EM) among
      Korean women. METHODS: A 73% of total women aged 30-69 at four districts in the
      KMCC (Korean Multi-center Cancer Cohort) was participated in this study during
      2002-2003. We selected 137 POF and 281 EM cases who had menopause before age 40
      and at age 40-44, respectively, and 1318 normal menopause (NM) controls that
      experienced menopause at age 45-60, and among them, selected idiopathic POF
      (n=84) and EM (n=261) after excluding surgical/medical menopause. We collected
      the information of premenopausal lifestyle and reproductive risk factors.
      Multivariate and polytomous logistic regression were used to estimate POF and EM
      risk and to differentiate POF and EM risk using ordinal and nominal scale.
      RESULTS: Cigarette smoking was associated with an increased risk of idiopathic
      POF (OR=1.82 [1.03-3.23]), whereas oral contraceptive use was associated with a
      reduced risk of natural EM (OR=0.62 [0.43-0.90]). Idiopathic POF risk by both
      factors differed from idiopathic EM risk (p-nominal<0.05). Factors related to
      ovulation, such as later menarche, irregular menstruation and longer breast
      feeding cumulatively reduced the risk of natural EM and POF (p-ordinal<0.05). In
      analysis including medical and surgical menopause, lung tuberculosis,
      hysterectomy, past cancers, and lower number of deliveries before menopause were
      associated with POF. CONCLUSIONS: Our findings indicate that etiology in POF
      development may partly differ from that in EM.

PMID- 17531411
TI  - Liquid spray formulations of xibornol by using self-microemulsifying drug
      delivery systems.
AB  - Xibornol is a lipophilic drug mainly used in Italy and Spain in spray dosage
      forms for the local treatment of infection and inflammation of the throat. Its
      poor water solubility makes difficult the development of aqueous formulations of
      the drug, thus giving rise to a limited number of stable and pharmaceutically
      accepted preparations. In fact, xibornol is actually marketed only as spray
      aqueous suspension. The aim of this work was to evaluate the possibility of
      developing a stable liquid formulation of the drug intended for oral spray
      administration using a self-microemulsifying drug delivery system (SMEDDS). These
      systems are able to adequately improve the drug solubility, allowing the
      introduction of relatively high concentration of drugs in the form of solution.
      Labrafil M1944, Labrafil M2125 and Labrafac CC were screened as oil phases,
      Labrasol and Labrafac PG as surfactants and Transcutol as co-surfactant. Pseudo
      ternary phase diagrams were constructed, by titration with the aqueous phase of
      different oil phases and surfactant/co-surfactant mixtures in order to identify
      the self-microemulsification region and the optimal micro-emulsion composition.
      Then, complete pharmaceutical formulations were prepared and evaluated for
      stability and viscosity properties. The final selected formulations, containing
      Labrafil M1944, Transcutol, Labrafac PG and a hydrophilic co-solvent (propylene
      glycol or PEG 200) allowed complete solubilization of the required xibornol
      concentration (3%, w/v) and showed physical good stability up to 2 months at 25
      and 4 degrees C, suitable viscosity and organoleptic properties.

PMID- 17531412
TI  - Effects of penetration enhancers on in vitro permeability of meloxicam gels.
AB  - Meloxicam (MLX) was formulated as a 0.3% hydroxypropylcellulose (Klucel) gel. The
      effect of four different combinations of co-solvents (ethanol, glycol-PEG-400,
      propylene glycol, and water) on MLX permeability was determined in vitro
      throughout isopropyl myristate (IPM)-saturated cellulose membranes. The gel
      consisting of 2.5% Klucel, propylene glycol, ethanol, and water (1:1:1) showed
      superior permeability properties and it was selected as the base-gel to
      investigate the effect of three levels of the penetration enhancers:
      dimethylsulfoxide (1, 5, and 10% DMSO), tween20 (1, 2, and 5% TW20), oleic acid
      (0.4, 1, and 5% OA), and menthol (1, 2.5, and 5% MT). In vitro permeability was
      determined throughout IPM-saturated cellulose membranes and human cadaver skin.
      DMSO and TW20 did not improve permeability of MLX compared to the control gel at
      any of the levels tested. Menthol produced a statistically significant (P<0.001),
      dose proportional increase in MLX flux with a peak at 5% (2.43+/-0.47
      microg/cm2/h). Conversely, addition of OA peaked at 1% but decreased at the
      higher level (5%). There was no significant difference between the MLX amount
      recovered in stratum corneum and dermis across the different formulations tested.
      These findings show that the 0.3% MLX gel formulation containing 5% menthol can
      possibly deliver therapeutically relevant doses of MLX.

PMID- 17531413
TI  - Sleep problems in Rett syndrome.
AB  - Rett syndrome (RTT) is a severe neurological disorder, affecting mainly females.
      It is generally caused by mutations in the MECP2 gene. Sleep problems are thought
      to occur commonly in Rett syndrome, but there has been little research on
      prevalence or natural history. An Australian population-based registry of cases
      born since 1976 has been operating since 1993, with current ascertainment at 300.
      The Australian Rett Syndrome Database (ARSD) consists of information about Rett
      syndrome cases including their functional ability, behaviour, sleep patterns,
      medical conditions and genotype. The cases range in age from 2 to 29 years. The
      aim of this study was to investigate the type and frequency of sleep problems,
      relationships with age and MECP2 mutation type and to evaluate changes over time.
      Parents or carers of the subjects with Rett syndrome were asked to complete a
      questionnaire about sleep problems on three separate occasions (2000, 2002 and
      2004). Regression modelling was used to investigate the relationships between
      sleep problems, age and mutation type. Sleep problems were identified in over 80%
      of cases. The prevalence of night-time laughter decreased with age and the
      prevalence of reported night-time seizures and daytime napping increased with
      age. The prevalence of sleep problems was highest in cases with a large deletion
      of the MECP2 gene and in those with the p.R294X or p.R306C mutations. Sleep
      problems are common in Rett syndrome and there is some variation with age and
      mutation type.

PMID- 17531414
TI  - Ampulla of Vater: comprehensive anatomy, MR imaging of pathologic conditions, and
      correlation with endoscopy.
AB  - Endoscopic retrograde cholangiopancreaticography with or without an endoscopic
      biopsy is the method for making a definitive diagnosis of disease in or around
      the ampulla of Vater. However, the endoscopic findings of neoplastic and non
      neoplastic conditions involving the perimapullary area may be similar and an
      endoscopic assessment is not entirely reliable for diagnosis. Recent MR and MRCP
      can allow the detection of lesions in a small complex structure such as the
      ampulla of Vater, and distinguish between an ampullary from periampullary lesion.
      This article reviews the normal anatomy of the ampulla of Vater, describes the
      role of MR in the detection and characterization of the lesion in or around the
      ampulla of Vater, and attempts to correlate them with ERCP.

PMID- 17531415
TI  - The imaging of coeliac disease and its complications.
AB  - Coeliac disease is a malabsorption syndrome in which dietary gluten damages the
      small bowel mucosa. Gluten contains gliadin, the primary toxic component that is
      primarily found in wheat, barley and rye products. The initial diagnosis of
      coeliac disease is usually made by endoscopic biopsy of the jejunum although
      sometimes imaging features can suggest the diagnosis. Once a diagnosis is made,
      patients need to be diet compliant and monitored for potential complications.
      Many complications are more common when dietary compliance is poor. Complications
      include intussusception (usually intermittent), ulcerative jejunitis,
      osteomalacia, cavitating lymph node syndrome and an increased risk of
      malignancies such as lymphoma, adenocarcinoma and squamous cell carcinoma.
      Radiological evaluation is central in the evaluation of these complications.
      Imaging may assist both in the diagnosis and staging of complications as well as
      enabling radiological guided percutaneous biopsy for complications of coeliac
      disease such as lymphoma. As coeliac disease is a relatively common disorder, it
      is likely that most radiologists will encounter the disease and its potential
      complications. The aim of this review article is to discuss and illustrate the
      role of modern radiology in evaluating the many presentations of this complex
      disease.

PMID- 17531416
TI  - CT localisation of small pulmonary nodules prior to thorascopic resection:
      Evaluation of a point marker system.
AB  - PURPOSE: To evaluated the utility of a 5-mm long point marker system for CT
      localisation of small pulmonary nodules prior to thorascopic resection. MATERIALS
      AND METHODS: Percutaneous localisation of 57 pulmonary nodules was performed with
      computed tomographic (CT) guidance in 52 patients. The size of the nodules ranged
      from 3mm to 20mm (mean: 9mm, median: 8mm). The mean distance of the outer rim to
      the pleura ranged from 3mm to 55mm (mean: 19mm, median: 15mm). A stainless steel,
      5-mm long point marker with a 30-cm long nylon suture and introducer system (21
      gauge) was firmly attached to the funnel at the proximal end of the marker.
      RESULTS: The point marker system was successfully placed without being dislodged
      in 56 out of the 57 lesions (98%) and served as a clear guide during
      thoracoscopy. In 10 out of 52 patients (19%), non-symptomatic pneumothorax cases
      were observed. In 6 out of 52 patients (10%), haemorrhages into the lung
      parenchyma were observed. In no case did insertion of the point marker system
      cause strong pain and require an analgesic agent to be added. No patients
      produced hemopysis or air emboli. All nodules, including a dislodgment case, were
      successfully resected and the suture served as a clear guide during thoracoscopy.
      Pathologic findings of nodules included 37 malignancies and 20 non-malignancies.
      CONCLUSION: The marker system used for thoracoscopic resection was a safe and
      useful procedure.

PMID- 17531417
TI  - Observer variability of Breast Imaging Reporting and Data System (BI-RADS) for
      breast ultrasound.
AB  - PURPOSE: To evaluate inter- and intra-observer variabilities in breast
      sonographic feature analysis and management, using the fourth edition of the
      Breast Imaging Reporting and Data System (BI-RADS). MATERIALS AND METHODS: We
      included 136 patients with 150 breast lesions who underwent breast ultrasound
      (US) and ultrasound-guided core needle biopsy. A pathological diagnosis was
      available for all 150 lesions: 77 (51%) malignant and 73 (49%) benign. Four
      radiologists retrospectively reviewed sonographic images of lesions twice within
      an 8-week interval. The observers described each lesion, using BI-RADS
      descriptors and final assessment. Inter- and intra-observer variabilities were
      assessed with Cohen's kappa statistic. Positive predictive value and negative
      predictive value (NPV) for final assessment were also calculated. RESULTS: For
      inter-observer agreements for sonographic descriptors, substantial agreement for
      lesion calcification and final assessment (kappa=0.61 for both), moderate
      agreement for lesion shape, orientation, boundary, and posterior acoustic
      features (kappa=0.49, 0.56, 0.59, and 0.49, respectively), and fair agreement for
      lesion margin and echo pattern (kappa=0.33 and 0.37, respectively) were obtained.
      For intra-observer agreement, substantial to perfect agreement was found for
      almost all lesion descriptors and final assessments. NPV for final assessment
      category 3 was 95%. Positive predictive value (PPV) for final assessment
      categorized as 4 or 5 were as follows: category 4a, 26%; category 4b, 89%;
      category 4c, 90%; and category 5, 97%. CONCLUSION: Because inter- and intra
      observer agreement with the BI-RADS lexicon for US is good, the use of BI-RADS
      lexicon can provide accurate and consistent description and assessment for breast
      US.

PMID- 17531418
TI  - Catalytic action of copper (II) ion on electrochemical oxidation of metformine
      and voltammetric determination of metformine in pharmaceuticals.
AB  - The catalytic effect of Cu(II) ion toward the oxidation of metformine (MET) have
      been observed in NH(3).H(2)O-NH(4)Cl buffer (pH 8.9; 0.1M). The oxidation peak
      current of imino-group in guanidino-group of MET at 0.95 V at carbon paste
      electrode (C/PE) in the presence of 2.0 x 10(-4)M Cu(II) ion was increased by
      about 20 times and the peak potential was unchanged compared with that in the
      absence of Cu(II) ion. Moreover, the oxidation peak current of MET at multiwalled
      carbon nanotube paste electrode (MWCNT/PE) was further increased by about three
      times compared with that at C/PE in the same medium. Based on the catalytic
      oxidation peak of MET by Cu(II) ion at MWCNT/PE, a voltammetric method for the
      determination of MET is developed. The peak current of the catalytic oxidation
      peak was proportional to MET concentration in the range of 2.0 x 10(-7) to 1.0 x
      10(-5)M. The detection limit was 6.7 x 10(-8)M.

PMID- 17531419
TI  - Column selection for pharmaceutical analyses based on a column classification
      using four test parameters.
AB  - This paper focuses on the usability of a previously developed column
      classification system, applied to pharmaceutical analyses. The separation of two
      drugs from their respective related substances was investigated on 65 new
      reversed-phase liquid chromatographic columns. The chromatographic procedure for
      fluoxetine hydrochloride was performed according to the method prescribed in the
      European Pharmacopoeia monograph while the separation of gemcitabine
      hydrochloride was carried out according to the United States Pharmacopeia
      monograph. It was shown that the column ranking system is a helpful tool in the
      selection of a suitable column.

PMID- 17531420
TI  - Simultaneous determination of four bioactive constituents in Liuwei Dihuang Pills
      by micellar electrokinetic chromatography.
AB  - A micellar electrokinetic chromatography (MEKC) method for the simultaneous
      determination of four bioactive constituents (morroniside, loganin, paeoniflorin
      and paeonal) in the Chinese patent medicine Liuwei Dihuang Pills is established.
      A carrier composed of 0.2M boric acid, 0.02 M sodium dodecyl sulfate (SDS) and 5%
      acetonitrile (pH was adjusted to 10.5 with 0.1 M NaOH) is found to be the most
      suitable electrolyte for this separation. The four constituents in Liuwei Dihuang
      Pills can be easily determined within 16 min. Optimization of separation is
      realized with the univariate approach by studying the effects of four factors
      relevant to run buffer on migration times.

PMID- 17531421
TI  - Determination of ochratoxin A in human urine by solid-phase microextraction
      coupled with liquid chromatography-fluorescence detection.
AB  - A new method for the determination of ochratoxin A (OTA) in human urine samples
      has been developed using solid-phase microextraction (SPME) interfaced with
      liquid chromatography-fluorescence detection (LC-FD). This method is simpler and
      cheaper compared to the most widely adopted clean-up procedures for OTA
      extraction from urine (usually based on immunoaffinity columns). Briefly, urine
      samples, diluted 1:5 with phosphate buffer (10 mM, pH 3), were partitioned
      against chloroform and the aqueous phase extracted by a
      polydimethylsiloxane/divinylbenzene (PDMS/DVB) fiber. The fiber was then
      "statically" desorbed, through a SPME interface, into a LC system operating in
      isocratic conditions. The linear range investigated in urine was 0.01-1 ng/ml.
      Within-day R.S.D.% in urine spiked at 0.1 and 1 ng/ml were 3.9 and 1.9,
      respectively, whereas the between-days R.S.D.% were 5.5 and 3.0, respectively.
      The limits of detection (LOD) and quantitation (LOQ) calculated at a signal-to
      noise ratio of 3 and 10 (noise calculated peak to peak on a blank chromatogram at
      the OTA retention time) were 0.01 and 0.05 ng/ml, respectively.

PMID- 17531422
TI  - Rapid method to study the sedimentation of a pigment suspension prepared for
      coating fluids.
AB  - Film coating fluids commonly contain a pigment suspension. The sedimentation of
      insoluble particles in the coating suspension is one of the main problems during
      the formulation of the coating fluid. The aims of this work were to investigate
      the suitability of an energy-dispersive X-ray fluorescence analyser for rapid
      measurement of the sedimentation of titanium dioxide in aqueous suspensions. The
      suspensions were produced with a high-speed Ultra-Turrax. The process factors
      evaluated were the stirring rate, time and volume, and the process of
      sedimentation of the pigment. The enrichment of the pigment at the bottom of the
      sample holder was followed by means of the very rapid method of energy-dispersive
      X-ray fluorescence analysis. It can be concluded that the sedimentation of the
      particles is described by the Weibull equation. With an appropriate combination
      of the factors, a threefold increase in the sedimentation time was achieved. The
      mathematically based information (sedimentation time, kinetics of sedimentation,
      etc.) is essential for an exact evaluation of the preparation of the coating
      fluid. The understanding of the process through use of this test method leads to
      the ability to identify the critical control points of film coating.

PMID- 17531423
TI  - Determination of rifampicin in human plasma and blood spots by high performance
      liquid chromatography with UV detection: a potential method for therapeutic drug
      monitoring.
AB  - A high performance liquid chromatography method has been developed that allows
      quantification of concentrations of rifampicin in human plasma and blood spots.
      Rifampicin and papaverine hydrochloride (internal standard) were extracted from
      plasma using a Strata-X-CW extraction cartridge. These analytes were also
      extracted into acetonitrile from blood spots dried onto a specimen collection
      card. The recovery of rifampicin from plasma and blood spots was 84.5% and 65.0%,
      respectively. Separation was achieved by HPLC on a Kromasil C(18) column with a
      mobile phase composed of ammonium acetate (20 mM, pH 4.0) and acetonitrile,
      delivered on a gradient programme. Optimum detection was at 334 nm. The assay was
      linear over the concentration range of 0.5-20 microg/ml. The limit of
      quantification was 0.5 microg/ml in plasma; 1.5 microg/ml in blood spots. Both
      intraday and interday precision data showed reproducibility (R.S.D.< or =8.0,
      n=9). Stability studies showed rifampicin was stable in plasma for up to 9h after
      thawing; the samples were also stable for up to 9h after preparation. Five
      patient samples were analysed using the methods described. A correlation was
      found between the concentrations of RIF in plasma and blood spots (r(2)=0.92).
      This method is proposed as a means of therapeutic drug monitoring of rifampicin
      in patients with tuberculosis.

PMID- 17531424
TI  - Determination of berberine in human plasma by liquid chromatography-electrospray
      ionization-mass spectrometry.
AB  - A liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS)
      method for the determination of berberine in human plasma using chlorobenzylidine
      as the internal standard (IS) has been developed and validated. The plasma
      samples were prepared by LLE and the analytes were chromatographically separated
      on a Hanbon Lichrospher 5-C18 HPLC column under gradient elution with a mobile
      phase consisted of acetonitrile and 10mm ammonium acetate buffer containing 0.1%
      formic acid. Berberine was determined with electrospray ionisation-mass
      spectrometry (ESI-MS). LC-ESI-MS was performed in the selected-ion monitoring
      (SIM) mode using target ions at M(+)m/z 336.1 for berberine and M(+)m/z 464.1 for
      the IS. Calibration curve was linear over the range of 0.020-3.0 ng/ml. The lower
      limit of quantification (LLOQ) was 0.020 ng/ml. The intra- and inter-run
      variability values were less than 6.7 and 7.7%, respectively. The method has been
      successfully applied to determine the plasma concentration of berberine in
      healthy Chinese volunteers.

PMID- 17531425
TI  - Determination of surface-adsorbed excipients of various types on drug particles
      prepared by antisolvent precipitation using HPLC with evaporative light
      scattering detection.
AB  - A common challenge in the development of new drug substances is poor dissolution
      characteristics related to low aqueous solubility. One approach to overcome this
      problem is antisolvent precipitation in the presence of polymers or surfactants,
      which may enhance the dissolution rate through reduced particle size and
      increased wettability. In this study, a simple method based on size exclusion
      chromatography (SEC) with evaporative light scattering detection (ELSD) was
      developed for the determination of polymers and surfactants adsorbed to drug
      particles prepared by antisolvent precipitation of the poorly water-soluble model
      drug Lu 28-179. Detection of many polymeric excipients and surfactants is
      problematic due to the lack of UV-absorbing chromophores, but ELSD proved
      successful for the direct determination of the investigated compounds. A mixed
      mode column was used to effectively separate each of the excipient structures
      from the drug. The mobile phase comprised acetonitrile-ammonium formate (20mM; pH
      6.5) (50:50, v/v) at a flow-rate of 0.6 ml/min. Qualification studies showed that
      the method was adequately sensitive and precise with limits of detection between
      0.72 and 4.32 microg/ml. Linearity of the calibration curves was achieved by log
      log modelling. The method was applied for determination of nine polymeric
      excipients and surfactants adsorbed to particles of the model drug. The extent of
      excipient adsorption varied between 0.07 and 1.39% (w/w) of the total particle
      weight.

PMID- 17531426
TI  - Purification method development for chiral separation in supercritical fluid
      chromatography with the solubilities in supercritical fluid chromatographic
      mobile phases.
AB  - A comprehensive approach was applied to develop a chiral purification method for
      an analyte that was found to be unusually difficult to scale-up in supercritical
      fluid chromatography (SFC). This was performed by studying major factors such as
      the solubility of an analyte in SFC mobile phases, impurity profiles, and cycle
      time. For this case study, the solubility in SFC mobile phase was measured by a
      packed column technique, coupled with a novel trapping mechanism to enhance
      measurement precision in SFC conditions. The solubility studies in SFC mobile
      phases suggested a couple of possible SFC mobile phases, in which the analyte
      would potentially be most soluble. The SFC methods were developed to purify a
      sample containing 15% of an impurity, after considering impurity profiles and
      cycle times of several potential methods in addition to SFC mobile phase
      solubility. An equal volume mixture of acetonitrile and ethanol was chosen for
      the final purification method, since this mixture demonstrated the relatively
      high SFC solubility among all solvent combinations with enhanced resolution
      between the analyte and the impurity as well as the shortest run time. The
      solubility of the compound was also determined in various organic solvents using
      a high throughput solubility screening system to better understand relative
      change of solubility from neat solution to SFC mobile phases.

PMID- 17531428
TI  - Equivalent survival in patients with advanced stage IB-II and III-IVA cervical
      cancer treated by adjuvant surgery following chemoradiotherapy.
AB  - OBJECTIVES: To evaluate survival in patients with advanced cervical cancer who
      underwent surgery after concurrent chemoradiotherapy. METHODS: One hundred and
      forty-four patients with biopsy-proven stage IB-IVA cervical cancer underwent
      adjuvant surgery after concurrent chemoradiotherapy. Surgical resection was
      classified as curative (no evidence of remaining disease after surgery) or
      palliative (remaining disease after surgery). Endpoints were pelvic control,
      overall survival (OS) and disease-free survival (DFS) at 5 and 10 years. Analysis
      included tumour FIGO stage, type of surgery (curative versus palliative), pelvic
      control, response to chemoradiotherapy and lymphatic status. RESULTS: Tumour FIGO
      stages were IB-II in 91 cases and III-IVA in 53 cases. Surgery was curative in
      127 cases. Pelvic control was achieved in 114 patients and was equivalent in
      stage IB-II and III-IVA patients. So far, 60 patients have died. The 5-year OS
      and DFS rates were, respectively, 57.6% [95% CI: 49.1-67.5] and 65% [95% CI: 56.2
      75]. OS was significantly affected by the type of surgery (p<2.10(-16)), the
      presence of tumoural residue (p=0.002) and the pelvic lymphatic status (p<0.001).
      DFS was affected by the pelvic (p=0.02) and para-aortic lymphatic status
      (p=0.009). No significant difference was observed between OS and DFS in stage IB
      II and III-IVA patients, whereas a macroscopic tumoural residue was observed in,
      respectively, 30.9 and 52.2% of cases (p=0.022). CONCLUSION: Survival rates were
      equivalent between patients with IB-II and III-IVA cervical cancer, suggesting
      that adjuvant surgery following chemoradiotherapy may improve local control.

PMID- 17531429
TI  - [Benefit of nutrition in children].
AB  - Surgery is a major cause of stress. Metabolic responses vary according to age but
      always include an initial catabolism. Postoperative nutrition support is not
      necessary during the first week except for the neonates. Oral route is the
      elective one. When parenteral nutrition is needed, specific paediatric nutriments
      and micronutriments should be preferred.

PMID- 17531430
TI  - [Tramadol for acute postoperative pain in children].
AB  - The real place of tramadol in the armatarium of postoperative analgesics in
      children remains to be defined. This paper presents a synthetic review of the
      present knowledge regarding the efficacy, dosage and possible routes of
      administration of tramadol to children in the postoperative period. The
      intravenous and oral routes are the most used. The perinervous routes (epidural,
      around peripheral nerves, skin infiltration) are controversial. Tramadol is a
      good alternative to NSAIDs and to morphine for moderate pain but its efficacy is
      variable due to the genetic polymorphism of its metabolism and possible drug
      interactions.

PMID- 17531431
TI  - [Therapeutic innovations in gastroesophageal reflux].
AB  - Proton-pump inhibitors remain the most effective treatment for relieving
      symptoms, healing lesions and preventing recurrences of gastroesophageal reflux
      (GER). Drugs inhibiting transient relaxation of the lower esophageal sphincter
      have an unfavorable benefit/risk ratio. Endoscopic methods developed in recent
      years have not been shown effective in trials versus sham procedures. Surgical
      treatment is effective in GER but causes frequent uncomfortable side effects that
      are difficult to treat.

PMID- 17531432
TI  - [Rheumatic manifestations of genetic hemochromatosis].
AB  - Rheumatic manifestations of genetic hemochromatosis are frequent. These
      manifestations are characterized by articular damage and osteoporosis. Clinicians
      must be aware of these presentations because they are sometimes the initial
      manifestation of hemochromatosis. Moreover, rheumatic pain causes substantial
      discomfort for patients and diminishes their quality of life.

PMID- 17531433
TI  - Transcriptional responses in spleens from mice exposed to Yersinia pestis CO92.
AB  - Yersinia pestis is one of the most threatening biological agents due to the
      associated high mortality and history of plague pandemics. Identifying molecular
      players in the host response to infection may enable the development of medical
      countermeasures against Y. pestis. In this study, microarrays were used to
      identify the host splenic response mechanisms to Y. pestis infection. Groups of
      Balb/c mice were injected intraperitoneally with 2-257CFU of Y. pestis strain
      CO92 or vehicle. One group was assessed for mortality rates and another group for
      transcriptional analysis. The time to death at the 8 and 257CFU challenge doses
      were 5.0+/-2.3 and 3.8+/-0.4 days, respectively. Gene profiling using Affymetrix
      Mouse Genome 430 2.0 Arrays revealed no probe sets were significantly altered for
      all five mice in the low-dose group when compared to the vehicle controls.
      However, 534 probe sets were significantly altered in the high dose versus
      vehicle controls; 384 probe sets were down-regulated and 150 probe sets were up
      regulated. The predominant biological processes identified were immune function,
      cytoskeletal, apoptosis, cell cycle, and protein degradation. This study provides
      new information on the underlying transcriptional mechanisms in mice to Y. pestis
      infection.

PMID- 17531434
TI  - A systematic review of prognostic/end-of-life communication with adults in the
      advanced stages of a life-limiting illness: patient/caregiver preferences for the
      content, style, and timing of information.
AB  - Evidence-based recommendations concerning how to discuss dying, life expectancy,
      and likely future symptoms with patients with a limited life expectancy and their
      families are lacking. The aim of this systematic review was to review studies
      regarding prognostic/end-of-life communication with adult patients in the
      advanced stages of a life-limiting illness and their caregivers. Relevant studies
      meeting the inclusion criteria were identified by searching computerized
      databases up to November 2004. One hundred twenty-three studies met the criteria
      for the full review, and 46 articles reported on patient/caregiver preferences
      for content, style, and timing of information. The majority of the research was
      descriptive. Although there were individual differences, patients/caregivers in
      general had high levels of information need at all stages of the disease process
      regarding the illness itself, likely future symptoms and their management, and
      life expectancy and information about clinical treatment options. Patient and
      caregiver information needs showed a tendency to diverge as the illness
      progressed, with caregivers needing more and patients wanting less information.
      Patients and caregivers preferred a trusted health professional who showed
      empathy and honesty, encouraged questions, and clarified each individual's
      information needs and level of understanding. In general, most
      patients/caregivers wanted at least some discussion of these topics at the time
      of diagnosis of an advanced, progressive, life-limiting illness, or shortly
      after. However, they wanted to negotiate the content and extent of this
      information.

PMID- 17531435
TI  - The end of life: a qualitative study of the perceptions of people over the age of
      80 on issues surrounding death and dying.
AB  - This study explored how elderly people living in the community perceive issues
      around death, dying, and the end of life using a qualitative grounded theory
      approach. Forty individuals aged between 80 and 89 years who were living alone in
      the community were interviewed and were identified through purposive and random
      sampling. The results revealed that issues associated with end of life included
      fear of how they would die, fear of becoming a burden to others, wanting to
      prepare for and have a choice with regard to where and when they die, and issues
      relating to assisted dying. The study demonstrated that issues relating to the
      end of life are a major concern for older people, but are seldom addressed by
      professionals. Listening to and understanding the views and experiences of the
      older age group regarding end-of-life care is needed if adequate person-centered
      care is to be delivered to this ever-growing population group.

PMID- 17531436
TI  - Preference for analgesic treatment for cancer pain among African Americans.
AB  - Over the past decade, there has been a surge of literature related to disparities
      in pain treatment between minority and non-minority patients. Conspicuously
      lacking from this body of literature is an effort to investigate the patient
      level factors that might account for undertreatment of pain among minorities. The
      present qualitative descriptive study was designed to gain a preliminary
      understanding of the preference for analgesic treatment for cancer pain among
      African Americans and the factors shaping these preferences. The sample (n=35)
      was recruited from three outpatient oncology clinics in the Mid-Atlantic region.
      Inclusion was based on self-identified African Americans, >18 years of age,
      diagnosed with solid tumors, with self-reported cancer pain of at least one
      month, and no history of major surgery in the past three months. The data were
      gathered using demographics, the Brief Pain Inventory-Long Form, and in-depth
      semistructured interviews. Qualitative findings revealed that despite having
      overt access to pain medications, considerable intra-ethnic heterogeneity existed
      in the preference for analgesia among this group of African Americans. The
      subjective preference for analgesics for cancer pain was tied to a number of
      covert factors such as meaning of cancer pain treatment, past experience with
      pain relief and analgesic side effects, fears of dependency and tolerance, and
      past experience with providers and the health system. These factors should be the
      focus of future inquiry.

PMID- 17531437
TI  - Exploring the relationship between fear of positive evaluation and social
      anxiety.
AB  - Cognitive-behavioral theorists have proposed that fear of negative evaluation is
      the core feature of social anxiety [Clark, D. M., & Wells, A. (1995). A cognitive
      model of social phobia. In: R. G. Heimberg, M. R. Liebowitz, D. A. Hope, & F. R.
      Schneier (Eds.), Social phobia: Diagnosis, assessment, and treatment (pp. 69-93).
      New York: Guilford Press; Rapee, R. M., & Heimberg, R. G. (1997). A cognitive
      behavioral model of anxiety in social phobia. Behavior Research and Therapy, 35,
      741-756]. However, we have previously hypothesized that fear of evaluation in
      general is important in social anxiety, including fears of positive as well as
      negative evaluation, and we developed the Fear of Positive Evaluation Scale
      (FPES; Weeks, J. W., Heimberg, R. G., & Rodebaugh, T. L. (2007). The Fear of
      Positive Evaluation Scale: Assessing a proposed cognitive component of social
      anxiety disorder. Manuscript submitted for review.) to test this hypothesis. The
      present paper reviews several studies conducted for the purpose of extending the
      empirical examination of the construct of fear of positive evaluation (FPE).
      Consistent with hypothesis, FPE was positively associated with discomfort in
      response to receipt of positive social feedback and negatively associated with
      perceived accuracy of the feedback received. Furthermore, the FPES correlated
      significantly with several measures related to social anxiety, and lower
      correlations with measures of other constructs provided evidence of discriminant
      validity. Thus, findings from the present series of studies add to the developing
      support for the hypothesis that fear of positive evaluation is important in
      social anxiety.

PMID- 17531438
TI  - Attention in selective mutism--an exploratory case-control study.
AB  - The aim of the study was to explore the association between selective mutism (SM)
      and attention. In SM social anxiety seems central but language impairment and
      motor problems are also reported. Attention problems have been described in
      parental behavioral ratings, while neuropsychological studies are lacking. A
      neuropsychological test (the Trail Making Test) and parental ratings of attention
      and anxiety problems were administered to a clinical sample of 23 children with
      SM (aged 7-16 years, 12 boys and 11 girls) and 46 non-referred matched controls.
      The SM group differed from controls on the Trail Making Test, but the group
      difference disappeared, when controlling for motor function and IQ. Parental
      ratings of attention problems were not significantly associated with the
      neuropsychological attention measure. Neuropsychological studies of attention
      controlled for IQ and motor function are needed as well as tests that measure
      different aspects of attention.

PMID- 17531439
TI  - A random model for mapping imprinted quantitative trait loci in a structured
      pedigree: an implication for mapping canine hip dysplasia.
AB  - Genetic imprinting may have played a more notable role in shaping embryonic
      development of plants, animals, and humans than previously appreciated.
      Quantitative trait loci that are imprinted (iQTL) exert monoallelic effects,
      depending on the parent of origin, which is an exception to the laws of Mendelian
      genetics. In this article, we present a modified random effect-based mapping
      model to use in a genome-wide scan for the distribution of iQTL that contribute
      to genetic variance for a complex trait in a structured pedigree. This model,
      implemented with the maximum likelihood method, capitalizes on a network of
      relatedness for maternally and paternally derived alleles through identical-by
      descent sharing, thus allowing for the discrimination of the genetic variances
      due to alleles derived from maternal and paternal parents. The model was employed
      to map iQTL responsible for canine hip dysplasia in a multihierarchical canine
      pedigree, founded with seven greyhounds and six Labrador retrievers. Of eight
      significant QTL detected, three, located on CFA1, CFA8, and CF28, were found to
      trigger significant parent-of-origin effects on the age of femoral capital
      ossification measured at the left and right hips of a canine. The detected iQTL
      provide important candidate regions for fine-mapping of imprinted genes and for
      studying their structure and function in the control of complex traits.

PMID- 17531440
TI  - Adolescent exposure to high-dose estrogen and subsequent effects on lactation.
AB  - Treatment with high-dose estrogens has been used to reduce the adult height of
      tall girls for many years. Short-term side effects on the breast have been
      reported but there have been no studies to investigate whether there are long
      term effects on lactation. This retrospective cohort study of 371 treated and 409
      untreated women asked about breastfeeding history. After adjusting for maternal
      age at first live-birth, treated women (4.4%) were no more likely than untreated
      women (4.1%) to not commence breastfeeding (RR 1.13, 95% CI 0.50-2.52). After
      adjusting for age, there was no significant difference in the average duration of
      breastfeeding between treated (median 41.1 weeks) and untreated women (median
      43.3 weeks) (p=0.77) for all live-births. Treated women were not significantly
      more likely to report physiological reasons for stopping breastfeeding than
      untreated women. Women treated with high-dose estrogens during adolescence
      appeared to be no different to untreated women in their ability to lactate.

PMID- 17531441
TI  - Predictive uncertainty in environmental modelling.
AB  - Artificial neural networks have proved an attractive approach to non-linear
      regression problems arising in environmental modelling, such as statistical
      downscaling, short-term forecasting of atmospheric pollutant concentrations and
      rainfall run-off modelling. However, environmental datasets are frequently very
      noisy and characterized by a noise process that may be heteroscedastic (having
      input dependent variance) and/or non-Gaussian. The aim of this paper is to review
      existing methodologies for estimating predictive uncertainty in such situations
      and, more importantly, to illustrate how a model of the predictive distribution
      may be exploited in assessing the possible impacts of climate change and to
      improve current decision making processes. The results of the WCCI-2006
      predictive uncertainty in environmental modelling challenge are also reviewed,
      suggesting a number of areas where further research may provide significant
      benefits.

PMID- 17531442
TI  - Identification of sequences that target BRCA1 to nuclear foci following
      alkylative DNA damage.
AB  - BRCA1 is a tumor suppressor involved in the maintenance of genome integrity.
      BRCA1 co-localizes with DNA repair proteins at nuclear foci in response to DNA
      double-strand breaks caused by ionizing radiation (IR). The response of BRCA1 to
      agents that elicit DNA single-strand breaks (SSB) is poorly defined. In this
      study, we compared chemicals that induce SSB repair and observed the most
      striking nuclear redistribution of BRCA1 following treatment with the alkylating
      agent methyl methanethiosulfonate (MMTS). In MCF-7 breast cancer cells, MMTS
      induced movement of endogenous BRCA1 into distinctive nuclear foci that co
      stained with the SSB repair protein XRCC1, but not the DSB repair protein gamma
      H2AX. XRCC1 did not accumulate in foci after ionizing radiation. Moreover, we
      showed by deletion mapping that different sequences target BRCA1 to nuclear foci
      induced by MMTS or by ionizing radiation. We identified two core MMTS-responsive
      sequences in BRCA1: the N-terminal BARD1-binding domain (aa1-304) and the C
      terminal sequence aa1078-1312. These sequences individually are ineffective, but
      together they facilitated BRCA1 localization at MMTS-induced foci. Site-directed
      mutagenesis of two SQ/TQ motif serines (S1143A and S1280A) in the BRCA1 fusion
      protein reduced, but did not abolish, targeting to MMTS-inducible foci. This is
      the first report to describe co-localization of BRCA1 with XRCC1 at SSB repair
      foci. Our results indicate that BRCA1 requires BARD1 for targeting to different
      types of DNA lesion, and that distinct C-terminal sequences mediate selective
      recruitment to sites of double- or single-strand DNA damage.

PMID- 17531443
TI  - Phospholipase C-gamma1 potentiates integrin-dependent cell spreading and
      migration through Pyk2/paxillin activation.
AB  - Phospholipase C-gamma1 (PLC-gamma1), which generates two second messengers,
      namely, inositol-1, 4, 5-trisphosphate and diacylglycerol, is implicated in
      growth factor-mediated chemotaxis. However, the exact role of PLC-gamma1 in
      integrin-mediated cell adhesion and migration remains poorly understood. In this
      study, we demonstrate that PLC-gamma1 is required for actin cytoskeletal
      organization and cell motility through the regulation of Pyk2 and paxillin
      activation. After fibronectin stimulation, PLC-gamma1 directly interacted with
      the cytoplasmic tail of integrin beta1. In PLC-gamma1-silenced cells, integrin
      induced Pyk2 and paxillin phosphorylation were significantly reduced and PLC
      gamma1 potentiated the integrin-induced Pyk2/paxillin activation in its enzymatic
      activity-dependent manner. In addition, specific knock-down of PLC-gamma1
      resulted in a failure to form focal adhesions dependent on fibronectin
      stimulation, which appeared to be caused by the suppression of Pyk2 and paxillin
      phosphorylation. Interestingly, PLC-gamma1 potentiated the activations of Rac,
      thus integrin-induced lamellipodia formation was up-regulated. Consequently, the
      strength of cell-substratum interaction and cell motility were profoundly up
      regulated by PLC-gamma1. Taken together, these results suggest that PLC-gamma1 is
      a key player in integrin-mediated cell spreading and motility achieved by the
      activation of Pyk2/paxillin/Rac signaling.

PMID- 17531444
TI  - Memory and phonological awareness in children with Benign Rolandic Epilepsy
      compared to a matched control group.
AB  - PURPOSE: In a previous study we demonstrated children with Benign Rolandic
      Epilepsy have normal intelligence and language ability. However, difficulties in
      verbal and visual memory and aspects of phonological awareness were found
      compared to normative data. To address the methodological limitations related to
      the use of normative data, we compared the same cohort of children with Benign
      Rolandic Epilepsy to a matched control group. METHOD: Controls (n=40) matched on
      age and gender to the Benign Rolandic Epilepsy cohort underwent
      neuropsychological assessment. The life functioning of the control group was
      assessed using a modified version of the Quality of Life in Childhood Epilepsy
      Questionnaire (QOLCE). RESULTS: The study confirmed the previous findings of
      memory and phonological awareness difficulties. In addition, the children with
      Benign Rolandic Epilepsy had significantly lower IQ scores than the matched
      control group. Paired sample t-tests showed that on 8 of 11 QOLCE scales,
      children with Benign Rolandic Epilepsy were rated by parents as having poorer
      life functioning compared to matched controls, including lower parental ratings
      on the subscales of memory and language. DISCUSSION: Benign Rolandic Epilepsy has
      an excellent seizure prognosis, but this study further emphasizes potential
      cognitive difficulties. Using an age and gender matched control group, the
      previous findings of memory and phonological awareness difficulties were
      validated. These problems in cognition were also identified by parents of
      children with Benign Rolandic Epilepsy as problematic and impacting upon the
      child's quality of life.

PMID- 17531445
TI  - Phylogenetic analysis of the Aspergillus niger aggregate in relation to feruloyl
      esterase activity.
AB  - Species of the Aspergillus niger aggregate are known to produce feruloyl
      esterases, enzymes involved in the degradation of cell wall polymers. However,
      species delineation is difficult in these fungi. We combined AFLP analysis with
      ITS rDNA and beta-tubulin sequencing to characterize the isolates of this
      aggregate in terms of feruloyl esterase production. A preliminary re-examination
      of isolates based on comparison of ITS rDNA and beta-tubulin sequences with those
      of typical taxa deposited in international collections led us to re-identify the
      isolates as members of the species A. niger, A. foetidus and A. tubingensis.
      Molecular clustering based on beta-tubulin data and AFLP analysis showed that the
      strains of A. niger formed a homogenous phylogenetic group distinguished by
      either zero or type A feruloyl esterase activity, while strains A. foetidus and
      A. tubingensis exhibited type B feruloyl esterase activity when grown on sugar
      beet pulp.

PMID- 17531446
TI  - Antimicrobial susceptibility of Gram-positive bacterial isolates from the Asia
      Pacific region and an in vitro evaluation of the bactericidal activity of
      daptomycin, vancomycin, and teicoplanin: a SENTRY Program Report (2003-2004).
AB  - Medical centres in eight countries in the Asia-Pacific region provided 2391
      isolates for the SENTRY Antimicrobial Surveillance Program during 2003-2004 to
      determine their susceptibility to several antimicrobial classes, including
      daptomycin. Daptomycin, vancomycin and teicoplanin minimum inhibitory
      concentrations (MICs) and minimum bactericidal concentrations (MBCs) were
      determined for 120 isolates of Staphylococcus aureus, which included wild-type
      (WT) methicillin-resistant S. aureus (MRSA) and strains with decreased
      susceptibility to vancomycin (hetero-vancomycin-intermediate S. aureus (hVISA)).
      Oxacillin-resistant staphylococcal isolates were much less susceptible to the
      other tested agents compared with oxacillin-susceptible strains. Vancomycin
      resistance was higher among Enterococcus faecium (10.3%) than Enterococcus
      faecalis (0.4%), and macrolide resistance was high both for beta-haemolytic
      (17.7%) and viridans group (48.7%) streptococci. Daptomycin (MIC for 90% of the
      organisms (MIC(90))=0.5-1mg/L) was two-fold more potent than vancomycin, with
      >99% susceptibility when tested against staphylococci. All tested isolates of E.
      faecalis (MIC(90)=2mg/L) and beta-haemolytic streptococci (MIC(90)=0.5mg/L) were
      susceptible to daptomycin. Daptomycin MIC and MBC values were slightly higher for
      the hVISA isolates compared with WT-MRSA, with MBC/MIC ratios of only 1-2 for
      both groups. The MBC/MIC ratio for vancomycin was often greater when tested
      against these strains, particularly hVISA. In contrast, teicoplanin MBC/MIC
      ratios were significantly higher, with many of the strains showing values
      consistent with tolerance (>or=32). Daptomycin was demonstrated to have excellent
      in vitro activity when tested against Gram-positive isolates collected from Asia
      Pacific countries, including hVISA strains.

PMID- 17531447
TI  - Prevalence, distribution and characterisation of ceftiofur resistance in
      Salmonella enterica isolated from animals in the USA from 1999 to 2003.
AB  - Third-generation cephalosporin (3GC) antimicrobials are the drugs of choice for
      treatment of salmonellosis in children. Salmonella isolated in the USA are
      assayed by the National Antimicrobial Resistance Monitoring System (NARMS) for
      resistance to antimicrobials including first-, second- and third-generation
      cephalosporins. From 1999 to 2003, 34,411 Salmonella were isolated from animals
      in the USA, of which 10.9% were found to be resistant to ceftiofur, a 3GC used in
      animals, whilst only 0.3% were resistant to ceftriaxone, a 3GC used in human
      medicine. Ceftiofur resistance rose from 4.0% in 1999 to 18.8% in 2003. Isolates
      from diagnostic laboratories had higher levels of resistance (18.5%), whereas
      levels in isolates from on-farm (3.4%) and slaughter (7.1%) sources were lower.
      Animals with a higher than average proportion of resistant Salmonella included
      cattle (17.6%), horses (19.2%) and dogs (20.8%). Levels in turkeys (6.8%),
      chickens (7.1%), eggs (3.6%) and swine (4.6%) were lower. Resistance varied
      between Salmonella serotypes. A few serotypes had significantly high levels, e.g.
      S. Newport was 70.4% ceftiofur resistant. Resistance was predominantly associated
      with bla(CMY-2)-encoding plasmids. These data suggest that the acquisition of
      resistance plasmids and the spread of specific serotypes harbouring these
      plasmids are driving the observed resistance to ceftiofur in Salmonella animal
      isolates.

PMID- 17531448
TI  - Molecular characterization of the first missense mutation in the fibrinogen
      Aalpha-chain gene identified in a compound heterozygous afibrinogenemic patient.
AB  - Congenital afibrinogenemia is a rare coagulopathy characterized by extremely low
      levels of functional and immunoreactive fibrinogen in plasma, associated with a
      hemorrhagic phenotype of variable severity. It is transmitted as an autosomal
      recessive trait and is invariantly associated with mutations affecting 1 of the 3
      fibrinogen genes (FGA, FGB, and FGG, coding for Aalpha, Bbeta, and gamma chain,
      respectively). Most genetic defects causing afibrinogenemia are truncating
      mutations, whereas only few missense mutations (6) have been identified so far,
      all located in FGB. In this study, the mutational screening of an afibrinogenemic
      Italian male identified the first missense mutation (Met51Arg) in FGA leading to
      afibrinogenemia. The patient was a compound heterozygote for a previously
      described frameshift mutation (1215delT) in the same gene. Met51Arg involves a
      residue located at the very beginning of the coiled-coil domain, in a region
      demonstrated to play a pivotal role in hexamer formation. In-vitro expression
      experiments showed that Met51Arg strongly reduces secretion of hexameric
      fibrinogen, whereas traces of not completely assembled trimeric intermediate were
      found in conditioned media. Western blot analysis on the proband's plasma
      confirmed the presence in vivo of the trimeric fibrinogen, supporting the
      hypothesis that Met51Arg prevents the final step of fibrinogen assembly.

PMID- 17531449
TI  - Motor behavioral and neuropathological deficits in mice deficient for normal
      prion protein expression.
AB  - It has been difficult to reconcile the absence of pathology and apparently normal
      behavior of mice lacking prion protein (PrP), referred to as Prnp(0/0) mice, with
      a mechanism of prion pathogenesis involving progressive loss of PrP(C)-mediated
      neuroprotection. However, here we report that Prnp(0/0) mice exhibit significant
      age-related defects in motor coordination and balance compared with mice
      expressing wild type Prnp on a syngeneic background, and that the brains of
      behaviorally-impaired Prnp(0/0) mice display the cardinal neuropathological
      hallmarks of spongiform pathology and reactive astrocytic gliosis that normally
      accompany prion disease. Consistent with the appearance of cerebellar ataxia as
      an early symptom in patients with Gerstmann-Straussler-Scheinker syndrome (GSS),
      an inherited form of human prion disease, motor coordination and balance defects
      manifested in a transgenic (Tg) mouse model of GSS considerably earlier than the
      onset of end-stage neurodegenerative disease. Our results are consistent with a
      mechanism in which loss of normal PrP(C) function is an important pathological
      component of prion diseases.

PMID- 17531450
TI  - FDG-PET and CSF phospho-tau for prediction of cognitive decline in mild cognitive
      impairment.
AB  - Specific patterns of cortical glucose metabolism disturbances and increased CSF
      phospho-tau (p-tau(181)) concentrations could be demonstrated to predict
      cognitive decline and shift to dementia in amnestic mild cognitive impairment
      (MCI). But comparisons of both diagnostic tools have not been undertaken so far.
      The aim of the study was to compare (18)F-fluoro-2-deoxy-d-glucose positron
      emission tomography (FDG-PET) findings and CSF phospho-tau (p-tau(181))
      measurements in the prediction of cognitive deterioration and conversion to
      dementia in MCI. During follow-up (mean 19 months) eight of 16 patients (50%)
      showed progressive cognitive decline, and four patients shifted to dementia.
      Pathological FDG-PET and elevated p-tau(181) levels both predicted deterioration.
      While p-tau(181) was highly sensitive for cognitive decline, FDG-PET was superior
      in predicting conversion to clinical dementia in MCI patients.

PMID- 17531451
TI  - Carbohydrate metabolism in Dioscorea esculenta (Lour.) Burk. tubers and Curcuma
      longa L. rhizomes during two phases of dormancy.
AB  - We have examined the changes in carbohydrate metabolism in food yam (Dioscorea
      esculenta (Lour.) Burk.) tubers and in an economically important spice cum
      medicinal plant turmeric (Curcuma longa L.) rhizomes under storage. Both
      specimens showed varied levels of dormancy and sprouting appeared at the end of
      dormant period. Harvested, fully matured tubers of yam and rhizomes of turmeric
      were stored in wooden boxes under the conditions of 28+/-2 degrees C temperature
      and 65-75% relative humidity (RH) in dark. The starch, sugars, enzymes of starch
      degradation, respiration, glycolysis, tricarboxylic acid (TCA) cycle and
      oxidative pentose phosphate pathway (PPP) were studied during 1-70 days after
      harvest (DAH). This investigation revealed that, the starch degradation and the
      enzymes involved, viz. alpha-amylases and starch phosphorylase showed a lower
      level of activity during early period of dormancy, while sugar content and
      enzymes of carbohydrate metabolism increased rapidly during sprouting. The
      isoenzymic profiles of alpha-amylases showed marked variations in these two
      phases. The key enzymes of glycolysis, TCA cycle and PPP, viz. aldolase, succinic
      dehydrogenase, malic dehydrogenase, glucose-6-phosphate dehydrogenase and 6
      phosphogluconate dehydrogenase were increased even before the visible appearance
      of sprouting and their activities were at their maximum during sprouting. Based
      of the observations the dormancy period may be distinctly divided into peak
      period of rest and presprouting period.

PMID- 17531452
TI  - [Primary results of antiretroviral treatment among HIV/AIDS infected children in
      Lome (Togo)].
AB  - Since 2004 in Togo HIV/AIDS infected children have, free of charge, access to
      antiretroviral drugs according to the national program. The aim of this study was
      to investigate the clinical, biological and prognosis aspects of anti-retroviral
      treatment on HIV/AIDS infected children. PATIENTS AND METHOD: We conducted a
      cross sectional study on 72 HIV/AIDS infected children with anti-retroviral
      treatment, under the supervision of clinicians within 3 associations specialized
      in the management of subjects infected by HIV/SIDA at Lome (Togo). RESULTS: The
      average age of children was 6 years 9 months. The middle age to HIV screening was
      4 years 2 months. The sex ratio was 1.05. The majority of these children (79.2%)
      were orphans of at least 1 of their parents. All the children were stemmed from
      families with modest income. The transmission mother to child was the way of HIV
      contamination found among all the children. To a certain extent, all the children
      were infected by the HIV 1. Most of the children (66.7%) receiving an
      antiretroviral treatment for at least 6 months were asymptomatic and had no more
      immunodeficiency. After 15 months, the children have gained 464 CD4/mm(3). The
      initial protocols antiretroviral prescribed among children were: zidovudine
      lamivudine-abacavir (36.1%), lamivudine-didanosine-nevirapine (30.5%), lamivudine
      stavudine-nevirapine (29.2%), zidovudine-lamivudine-didanosine (4.2%). The
      digestive disorders have been the first side effects (83.4%). The rate of good
      observance was middle (51%) and lowered with the increased age of children, and
      the period of the anti-retroviral treatment. CONCLUSIONS: Antiretroviral
      treatment among HIV/AIDS infected children is giving good results in Togo. But
      many efforts remain to increase the number of beneficiaries.

PMID- 17531453
TI  - [Actual antimicrobial chemotherapy prescription in infant and child].
AB  - Antimicrobial chemotherapy prescription should take into account the following
      items: 1) accurate diagnosis (most often clinical) and definition criteria of
      infectious diseases; 2) treatment justification; 3) confirmation of a bacterial
      etiology (now facilitated in some clinical situations by broadly available easy
      to-use rapid diagnosis tests); 4 evidence-based antimicrobial choices; 5)
      modalities of prescriptions guided by official authorities (guidelines from
      French agency of medicinal products).

PMID- 17531454
TI  - Aquatic tetrasporoblastic microsporidia from caddis flies (Insecta, Trichoptera):
      characterisation, phylogeny and taxonomic reevaluation of the genera Episeptum
      Larsson, 1986, Pyrotheca Hesse, 1935 and Cougourdella Hesse, 1935.
AB  - Seven microsporidian species infecting caddis fly larvae, corresponding to
      conventional genera Episeptum, Pyrotheca and Cougourdella were studied using
      light and electron microscopy. Parts of their small subunit, ITS and large
      subunit ribosomal RNA genes were sequenced and compared with sequences of rDNA
      obtained from syntype slides of Cougourdella polycentropi Weiser 1965 and
      Pyrotheca sp. from Hydropsyche pellucidula. All studied caddis fly microsporidia
      form a closely related group. Their developmental stages in trichopteran hosts
      are restricted to fat body cells and oenocytes and have isolated nuclei. In late
      merogony, uninucleate meronts and binucleate plasmodia are formed. In sporogony a
      sporogonial plasmodium with four nuclei gives rise by rosette-like budding to
      four sporoblasts within a non-persistent sporophorous vesicle. Sporoblasts mature
      into pyriform to lageniform spores. The shape and size of spores, the number of
      polar filament coils, the structure of the polaroplast and of the exospore,
      together with morphometric characters present a set of markers unique for
      respective species. Four new species are established. The new genus Paraepiseptum
      is proposed to replace the tetrasporoblastic Pyrotheca and Cougourdella species
      from caddis flies. The genus Episeptum is redefined. Field and laboratory
      examinations as well as the phylogenetic position within the aquatic clade of
      microsporidia suggest that the life cycle of trichopteran microsporidia probably
      involves an alternate (copepod?) host and (or) transovarial transmission.

PMID- 17531455
TI  - Seven-year time course of lung function, symptoms, health-related quality of
      life, and exercise tolerance in COPD patients undergoing pulmonary rehabilitation
      programs.
AB  - AIM: To evaluate the long-term course of outcome indexes in patients with chronic
      obstructive pulmonary disease (COPD) undergoing repeated pulmonary rehabilitation
      programs (PRP). DESIGN: Prospective, observational study. SETTING: Pulmonary
      Rehabilitation Center. PATIENTS: Forty-eight COPD patients (M 33, age 59.6+/-8.9
      years, forced expiratory volume in 1s (FEV(1)) 58+/-16% predicted, DLCO 71+/-17%
      predicted.) undergoing 5 Day-Hospital based PRPs in a period of 7.2+/-0.8 years.
      MEASUREMENTS: Lung function, exercise capacity (incremental cycloergometry, test
      6-minute walking test (6MWD)), dyspnoea (Baseline-BDI and Transitional-TDI
      Dyspnoea Index and Medical Research Council score-MRC), health-related quality of
      life (HRQL) (St. George Respiratory Questionnaire (SGRQ), and the derived BODE
      index were assessed pre and post each PRP. RESULTS: During follow-up, patients
      showed a 18+/-22 (mean+/-SEM)ml/year FEV(1) decline (95%CI: -24.4 to 11.6;
      p<0.001). Exercise tolerance and BDI remained stable over time whereas SGRQ
      improved (DeltaSGRQ total score: -9.6+/-14%, p<0.001). BODE index significantly
      worsened (from 1.27+/-1.14 to 1.98+/-1.64; p<0.001), being this change mainly
      attributable to worsening in FEV(1). Each PRP elicited significant improvement in
      exercise capacity, dyspnoea, SGRQ and BODE score. Post-PRP improvements in 6MWD,
      MRC and TDI were higher after the first three than after the last two PRPs
      (p<0.001), whereas the greatest gain in SGRQ was observed after PRP1 and then it
      was lower (p<0.03) but stable in the following periods of observation.
      CONCLUSION: Despite progressive lost in effectiveness of repeated PRP, COPD
      patients undergoing those programs do not show any significant worsening in
      exercise tolerance, dyspnoea and HRQL along a period of 7 years.

PMID- 17531456
TI  - Fish oil decreases matrix metalloproteinases in knee synovia of dogs with
      inflammatory joint disease.
AB  - This study was designed to determine whether dietary fish oil affects the
      expression and activity of matrix metalloproteinases (MMP), tissue inhibitors of
      MMP-2 (TIMP-2) and urokinase plasminogen activator (uPA) in synovial fluid from
      dogs with spontaneously occurring stifle (knee) instability in a single hind limb
      resulting from acute cranial cruciate ligament (CCL) injury. Two groups of 12
      dogs were fed diets from 1 week prior to surgery on the affected knee to 56 days
      post-surgery. The fish oil and control diets provided 90 and 4.5 mg,
      respectively, of combined eicosapentaenoic acid (EPA) and docosahexaenoic acid
      (DHA)/kg body weight per day. Plasma and synovial fluid, from both surgical and
      nonsurgical knee joints, were obtained at start of the diet (-7), surgery day (0)
      and 7, 14, 28 and 56 days post-surgery. Plasma total EPA and DHA were
      significantly increased, and plasma total arachidonic acid (AA) was significantly
      decreased by the fish oil diet. In synovial fluid from the nonsurgical knee, fish
      oil treatment significantly decreased proMMP-2 expression at Days 7 and 14, and
      proMMP-9 expression at Day 56, and uPA activity at 28 days and significantly
      increased TIMP-2 expression at Days 7 and 28. There were no differences in MMP
      expression or activity, TIMP-2 expression and uPA activity in the surgical joint
      synovial fluid at any time throughout the study. These results suggest that
      dietary fish oil may exert beneficial effects on synovial fluid MMP and TIMP-2
      equilibrium in the uninjured stifle of dogs with unilateral CCL injury.

PMID- 17531457
TI  - Egg yolk improves lipid profile, lipid peroxidation and retinal abnormalities in
      a murine model of genetic hypercholesterolemia.
AB  - Carotenoids are believed to inhibit oxidative stress. We investigated the
      protective effect of lutein and egg yolk supplementation on systemic and retinal
      alterations in apolipoprotein E-deficient (apoE-/-) mice, an experimental model
      of hypercholesterolemia and cardiovascular disease. Three-month-old wild-type and
      apoE-/- mice received one of the following: vehicle, lutein (0.09 mg/kg per day)
      or egg yolk (0.8 g/kg per day), by gastroesophageal cannula for 3 months. Total
      cholesterol (TC), triacylglycerol (TG) and lipid peroxidation (TBARS) were
      measured in plasma. TBARS levels were also determined in retinal homogenates.
      Ultrastructural morphology was analyzed by electron microscopy. ApoE-/- mice,
      with increased TC and TG concentrations, had higher systemic (P<.05) and retinal
      (P<.01) levels of lipid peroxidation than wild-type strains. Electron microscopy
      showed ultrastructural alterations (basal laminar deposits, open intercellular
      junctions, increased cytoplasmic vacuoles) in the retinas from apoE-/- mice. Egg
      yolk significantly reduced plasma TG (P<.05) and, without changes in TC,
      decreased plasma lipid peroxidation (P<.05). Lutein supplementation marginally
      affected the parameters. Less severe retinal ultrastructural alterations were
      observed in apoE-/- mice receiving either egg yolk or lutein. In the apoE-/-
      mouse model, egg yolk improved the lipid profile and reduced systemic lipid
      peroxidation (P<.05). While lutein and egg yolk did not seem to reduce retinal
      lipid peroxidation, a reduction in retinal ultrastructural alterations was
      observed.

PMID- 17531458
TI  - Acute and chronic effects of some dietary bioactive compounds on folic acid
      uptake and on the expression of folic acid transporters by the human trophoblast
      cell line BeWo.
AB  - Folic acid (FA) is a vitamin that acts as a coenzyme in the biosynthesis of
      purine and pyrimidine precursors of nucleic acids, which are critically important
      during pregnancy. Our group has previously shown that both reduced folate carrier
      (RFC1) and folate receptor alpha (FRalpha) seem to be involved in the uptake of
      [3H]folic acid ([3H]FA) by a human trophoblast cell line (BeWo) and by human
      primary cultured cytotrophoblasts. Our aim was to study the interaction between
      FA and some nutrients/bioactive substances. For this, we tested the acute and
      chronic effects of some dietary compounds on [3H]FA apical uptake and on the
      expression of both RFC1 and FRalpha mRNA in BeWo cells. Our results show that
      [3H]FA uptake was significantly reduced by acute exposure to epicatechin,
      isoxanthohumol (1-400 microM) or theophylline (0.1-100 microM); isoxanthohumol
      seemed to act as a competitive inhibitor, whereas epicatechin and theophylline
      caused an increase in both Km and Vmax. On the other hand, [3H]FA uptake was
      significantly increased by chronic exposure to xanthohumol, quercetin or
      isoxanthohumol (0.1-10 microM), and this increase does not seem to result from
      changes in the level of RFC1 or FRalpha gene expression. Moreover, [3H]FA uptake
      was significantly reduced by chronic exposure to ethanol (0.01%). This reduction
      seems to be, at least in part, due to a reduction in FRalpha expression. These
      results are compatible with an association between a deficient FA supply to the
      placenta/fetus and ethanol toxicity in pregnancy.

PMID- 17531459
TI  - Chromium picolinate and conjugated linoleic acid do not synergistically influence
      diet- and exercise-induced changes in body composition and health indexes in
      overweight women.
AB  - This study assessed the effects of combined chromium picolinate (CP) and
      conjugated linoleic acid (CLA) supplementation on energy restriction and exercise
      induced changes in body composition, glucose metabolism, lipid lipoprotein
      profile and blood pressure in overweight, premenopausal women. For 12 weeks, 35
      women [age 36+/-1 years (mean+/-S.E.M.); BMI 28.0+/-0.5 kg/m2] were counseled to
      consume a 2092 kJ/day (500 kcal/day) energy deficit diet and performed 30 min of
      moderate-intensity walking or jogging 5 days/week. The women were randomly
      assigned to ingest either CP-CLA [400 mug chromium (Cr), 1.8 g CLA in 2.4 g
      tonalin oil, n=19] or placebo (<0.1 microg Cr, 2.4 g canola oil, n=16). Compared
      to baseline, urinary Cr excretion increased 22-fold, plasma CLA isomer 18:2
      (c9,t11) content increased 79% and plasma CLA isomer 18:2 (t10,c12) became
      detectable in CP-CLA and were unchanged in Placebo. Over time, body weight
      decreased 3.5+/-0.5% (CP-CLA -2.6+/-0.5; placebo -2.5+/-0.5 kg) and fat mass
      decreased 8.9+/-1.3% (CP-CLA -2.7+/-0.5, placebo -2.4+/-0.5 kg), with no
      differences in responses between groups. Fasting blood hemoglobin A1c, plasma
      glucose and insulin, a homeostatic assessment of insulin resistance, serum total
      cholesterol (CHOL), high-density lipoprotein cholesterol (HDL), low-density
      lipoprotein cholesterol, triacylglycerol (TG), CHOL/HDL ratio, TG/HDL ratio and
      sitting systolic and diastolic blood pressures were not changed over time or
      influenced by CP-CLA. The use of a combined CP and CLA supplement for 3 months
      does not affect diet- and exercise-induced changes in weight and body composition
      or improve indexes of metabolic and cardiovascular health in young overweight
      women.

PMID- 17531460
TI  - Vitamin D and aging: old concepts and new insights.
AB  - Aging is a complex biological process driven by a selective class of molecules
      and pathways that affect overall deterioration of physiological functions to
      increase the risk of age-related diseases. A role of vitamin D in mammalian aging
      is well documented. Since vitamin D has an essential role in bone formation and
      mineralization, its deficiency results in impaired bone mineralization, such as
      rickets in children, osteomalacia in adults and osteoporosis in the aged
      population. Vitamin D replacement therapy therefore is one of the most commonly
      prescribed treatments for the elderly. Recent studies using genetically altered
      mouse models, such as in Fgf-23(-/-) and klotho mutant mice, that exhibit altered
      mineral ion metabolism due to high vitamin D activities showed features of
      premature aging that include atherosclerosis, emphysema, osteopenia/osteoporosis,
      hypogonadism, soft tissue calcifications and generalized atrophy of organs; the
      pathologic effects of vitamin D in these mouse models are obvious, as diminution
      or genetic ablation of the vitamin D pathway ameliorated most of the above
      mentioned phenotypes, by reversing mineral ion metabolism, and the resultant
      effect being prolonged survival of the mutant mice. These in vivo mouse studies,
      although subject to further molecular characterization, add new insights into the
      role of vitamin D in aging.

PMID- 17531461
TI  - Increased L-CPT-1 activity and altered gene expression in pancreatic islets of
      malnourished adult rats: a possible relationship between elevated free fatty acid
      levels and impaired insulin secretion.
AB  - Intrauterine growth restriction is associated with chronically elevated levels of
      serum fatty acids and reduced glucose-stimulated insulin secretion. Lipid
      metabolism in pancreatic beta cells is critical for the regulation of insulin
      secretion, and the chronic exposure to fatty acids results in higher palmitate
      oxidation rates and an altered insulin response to glucose. Using a rat model of
      isocaloric protein restriction, we examined whether pre- and postnatal protein
      malnutrition influences the properties of pancreatic islet carnitine
      palmitoyltransferase-1 (liver isoform, L-CPT-1), a rate-limiting enzyme that
      regulates fatty acid oxidation in mitochondria. The activity of L-CPT-1 in
      pancreatic islets increased in the low protein (LP), although the L-CPT-1 mRNA
      levels were unaffected by malnutrition. The susceptibility of enzyme to
      inhibition by malonyl-CoA was unaltered and the content of malonyl-CoA was
      reduced in LP cells. Because the mitochondrial oxidation of fatty acids is
      related to the altered expression of a number of genes encoding proteins involved
      in insulin secretion, the levels of expression of insulin and GLUT-2 mRNA were
      assessed. A reduced expression of both genes was observed in malnourished rats.
      These results provide further evidence that increased L-CPT-1 activity and
      changes in gene expression in pancreatic islets may be involved in the reduced
      insulin secretion seen in malnourished rats.

PMID- 17531462
TI  - Evaluation of leaching and extraction procedures for soil and waste.
AB  - Laboratory leaching tests may be used for source term determination as a basis
      for risk assessment for soil-groundwater pathways on contaminated sites. In order
      to evaluate different leaching procedures, batch extraction tests and percolation
      tests were performed using three reference materials produced from contaminated
      soil, demolition waste and municipal solid waste incinerator bottom ash. Emphasis
      was placed on the investigation of the leachability of the heavy metals copper
      and chromium, polycyclic aromatic hydrocarbons (PAHs) and the anions chloride and
      sulfate. Significant discrepancies between column experiments and
      batch/extraction tests were found for the release of PAHs and to a lesser extent
      for the heavy metals Cu and Cr. Additionally interlaboratory comparisons were
      conducted based on different leaching tests with the reference materials and
      evaluated using the criteria of comparability and reproducibility. The best
      reproducibility was achieved for all investigated substances in column tests. The
      reproducibility of batch tests was acceptable except for PAHs. The results from
      the experimental work will help establish standardized and feasible laboratory
      procedures as fundamental for substance specific risk assessment of contaminated
      sites.

PMID- 17531463
TI  - Influence of treatment techniques on Cu leaching and different organic fractions
      in MSWI bottom ash leachate.
AB  - The leaching of heavy metals, such as copper, from municipal solid waste
      incinerator (MSWI) bottom ash is of concern in many countries and may inhibit the
      beneficial reuse of this secondary material. Previous studies have focused on the
      role of dissolved organic carbon (DOC) on the leaching of copper. Recently, a
      study of the Energy Research Centre of The Netherlands (ECN) showed fulvic acid
      type components to exist in the MSWI bottom ash leachates and to be likely
      responsible for the generally observed enhanced copper leaching. These findings
      were verified for a MSWI bottom ash (slashed circle 0.1-2 mm) fraction from an
      incinerator in Flanders. The filtered leachates were subjected to the IHSS
      fractionation procedure to identify and quantify the fractions of humic acid
      (HA), fulvic acid (FA) and hydrophilic organic carbon (Hi). The possible
      complexation of fulvic acid with other heavy metals (e.g., lead) was also
      investigated. The identified role of fulvic acids in the leaching of copper and
      other heavy metals can be used in the development of techniques to improve the
      environmental quality of MSWI bottom ash. Thermal treatment and extraction with a
      0.2 M ammonium-citrate solution were optimized to reduce the leaching of copper
      and other heavy metals. The effect of these techniques on the different fractions
      of organic matter (HA, FA, Hi) was studied. However, due to the obvious drawbacks
      of the two techniques, research is focused on finding other (new) techniques to
      treat MSWI bottom ash. In view of this, particle size-based separation was
      performed to evaluate its effect on heavy metal leaching and on HA, FA and Hi in
      MSWI bottom ash leachates.

PMID- 17531464
TI  - The potential for aeration of MSW landfills to accelerate completion.
AB  - Landfilling is a popular waste disposal method, but, as it is practised
      currently, it is fundamentally unsustainable. The low short-term financial costs
      belie the potential long-term environmental costs, and traditional landfill sites
      require long-term management in order to mitigate any possible environmental
      damage. Old landfill sites might require aftercare for decades or even centuries,
      and in some cases remediation may be necessary. Biological stabilisation of a
      landfill is the key issue; completion criteria provide a yardstick by which the
      success of any new technology may be measured. In order for a site to achieve
      completion it must pose no risk to human health or the environment, meaning that
      attenuation of any emissions from the site must occur within the local
      environment without causing harm. Remediation of old landfill sites by aerating
      the waste has been undertaken in Germany, the United States, Italy and The
      Netherlands, with considerable success. At a pilot scale, aeration has also been
      used in newly emplaced waste to accelerate stabilisation. This paper reviews the
      use of aerobic landfill worldwide, and assesses the ways in which the use of
      aerobic landfill techniques can decrease the risks associated with current
      landfill practices, making landfill a more sustainable waste disposal option. It
      focuses on assessing ways to utilise aeration to enhance stabilisation. The
      results demonstrated that aeration of old landfill sites may be an efficient and
      cost-effective method of remediation and allow the date of completion to be
      brought forward by decades. Similarly, aeration of newly emplaced waste can be
      effective in enhancing degradation, assisting with completion and reducing
      environmental risks. However, further research is required to establish what
      procedure for adding air to a landfill would be most suitable for the UK and to
      investigate new risks that may arise, such as the possible emission of non
      methane organic compounds.

PMID- 17531465
TI  - Sentinel lymph node biopsy and non-sentinel node involvement in special type
      breast carcinomas with a good prognosis.
AB  - This study aimed at identifying factors related to sentinel lymph node (SLN)
      involvement in patients with tubular, cribriform, mucinous or papillary breast
      carcinoma and those related to non-SLN metastases if an SLN was positive.
      Multivariate analyses involved logistic and stepwise regressions. The SLNs
      harboured metastases in 85 of 572 cases, 78 of whom underwent axillary
      dissection; 19 presented non-SLN positive disease. Lack of lymphovascular
      invasion, a tumour size < or = 10 mm and a single SLN removed were the factors
      predicting an SLN metastasis rate <10%, and patients with these features could be
      candidates for no surgical axillary staging. A positive SLN proportion of < or =
      50% and no lymphovascular invasion were associated with a <10% rate of non-SLN
      invasion; patients with a positive SLN and these features could be candidates for
      the omission of completion axillary dissection. The opposite presentation of
      these factors would mandate SLN biopsy and axillary dissection, respectively.

PMID- 17531466
TI  - Occurrence of both bladder and prostate cancer in five cancer registries in
      Belgium, The Netherlands and the United Kingdom.
AB  - OBJECTIVE: To assess the occurrence of both bladder and prostate tumours in five
      well defined cancer registries. METHODS: Anonymous data were provided from each
      cancer registry on all male bladder and prostate cancers (invasive and non
      invasive). Poisson regression was used to model the rate of developing the second
      primary tumour and generated incidence rate ratios (RRs) with 95% confidence
      intervals. RESULTS: For bladder cancer and prostate cancer as first diagnosis,
      there was an excess risk to develop the second neoplasm. The RR decreased with
      increasing age of the patients. No effect of the initial treatment of the first
      neoplasm was found. CONCLUSION: This analysis found an excess risk to develop
      prostate cancer in bladder cancer patients younger than 70 years and the first
      year of follow-up after the diagnosis of bladder cancer. This may be due to
      detection bias, although a common aetiology may also be present.

PMID- 17531467
TI  - Upregulation of Wilms' tumour gene 1 (WT1) in uterine sarcomas.
AB  - AIM: Overexpression of Wilms' tumour gene (WT1) has been proven in several
      tumours. Previous research of our group on the cell cycle of uterine
      leiomyosarcoma (LMS) and carcinosarcoma (CS) suggested a possible role for WT1.
      We therefore intended to further explore the expression pattern of WT1 in uterine
      sarcomas. METHODS: 27 CS, 38 LMS, 15 endometrial stromal sarcomas (ESS) and seven
      undifferentiated sarcomas (US) were collected. WT1 expression was evaluated by
      immunohistochemistry (IHC) in 87 samples, by RT-PCR (m-RNA expression) in 23
      random selected samples and by Western blotting in 12 samples, separating
      cytoplasmic and nuclear proteins. A pilot study to detect mutations (exons 7-10)
      was performed on eight samples. RESULTS: IHC showed WT1 positivity in 12/27 CS,
      29/38 LMS, 7/15 ESS and 4/7 US. All-but-one sample had a positive RT-PCR. All
      Western blottings were positive with more cytoplasmic expression in 9/12 cases.
      No mutations were found. CONCLUSIONS: WT1 is overexpressed in uterine sarcomas.
      Since increased levels of mRNA determine the biological role, WT1 might
      contribute to uterine sarcoma tumour biology.

PMID- 17531468
TI  - Telomerase activity in sputum and telomerase and its components in biopsies of
      advanced lung cancer.
AB  - PURPOSE: In this study, we explored the diagnostic utility of sputum telomerase
      activity as a non-invasive biomarker of lung cancer. In biopsies of lung cancer,
      the relationship of telomerase activity to telomerase reverse transcriptase
      (hTERT) and telomerase RNA component (hTERC) and to c-Myc expression was also
      evaluated. METHODS: Paired biopsy and sputum samples were evaluated for
      telomerase activity by the telomerase repeat amplification protocol (TRAP) assay
      in 34 cases of lung cancer and in 30 control subjects without any evidence of
      lung cancer. hTERT and hTERC transcript expression was evaluated in 42 cases of
      lung cancer and compared to telomerase activity and c-Myc transcript expression.
      RESULTS: Telomerase activity was present in 85.2% of biopsies and in 67.6% of
      paired sputum with a good concordance. Three out of the 30 negative controls
      showed a weak telomerase activity, all of whom had sarcoidosis. Thus, sputum
      telomerase activity had sensitivity, specificity, Negative Predictive Value and
      Positive Predictive Value of 67.6%, 90%, 71% and 88.46%, respectively. The hTERT
      levels correlated to the telomerase activity but not to the c-Myc oncogene
      expression. CONCLUSIONS: In lung cancer, sputum telomerase activity is a
      candidate non-invasive biomarker of malignancy.

PMID- 17531469
TI  - The role of microRNAs in cancer: no small matter.
AB  - MicroRNAs are a recently discovered class of small, evolutionarily conserved, RNA
      molecules that negatively regulate gene expression at the post-transcriptional
      level. Mature microRNAs of approximately 20-22 nucleotides are formed from longer
      primary transcripts by two sequential processing steps mediated by a nuclear
      (Drosha) and a cytoplasmic (Dicer) RNAse III endonuclease. In the context of a
      protein complex, the RNA-induced silencing complex (RISC), microRNAs base-pair
      with target messenger RNA sequences causing translational repression and/or
      messenger RNA degradation. MicroRNAs have been implicated in the control of many
      fundamental cellular and physiological processes such as tissue development,
      cellular differentiation and proliferation, metabolic and signalling pathways,
      apoptosis and stem cell maintenance. Mounting evidence indicates that microRNAs
      also play a significant role in cellular transformation and carcinogenesis acting
      either as oncogenes or tumour suppressors. This review briefly introduces
      microRNAs in a historical perspective and focuses on the biogenesis of microRNAs,
      their mode of action, mammalian microRNA functions with emphasis on their
      involvement in disease - particularly cancer - and their potential therapeutic
      use.

PMID- 17531470
TI  - Enhanced antibiotic activity of Xenorhabdus nematophila by medium optimization.
AB  - Nutrition had highly influence on the antibiotic production by Xenorhabdus
      nematophila YL001. Glucose and peptone were identified as the best carbon and
      nitrogen sources that significantly affected antibiotic production using one
      factor-at-a-time approach. Response surface methodology was applied to optimize
      the medium constituents (Glucose, peptone and minerals) for antibiotic production
      by X. nematophila YL001. Higher antibiotic activity (328.9 U/ml) was obtained
      after optimizing medium components. The optimal levels of medium components were
      (g/l): glucose 6.13, peptone 21.29, MgSO(4).7H(2)O 1.50, (NH(4))(2)SO(4) 2.46,
      KH(2)PO(4) 0.86, K(2)HPO(4) 1.11 and Na(2)SO(4) 1.72. An overall 16% and 35%
      increase in antibiotic activity were obtained as compared with mean observed
      response (283.7U/ml) at zero level of all variables and YSG medium.

PMID- 17531471
TI  - Antioxidant potentials and rosmarinic acid levels of the methanolic extracts of
      Salvia virgata (Jacq), Salvia staminea (Montbret & Aucher ex Bentham) and Salvia
      verbenaca (L.) from Turkey.
AB  - This study was designed to examine the in vitro antioxidant activities and
      rosmarinic acid levels of the methanol extracts of Salvia virgata, Salvia
      staminea and Salvia verbenaca. The extracts were screened for their possible
      antioxidant activity by two complementary test systems, namely DPPH free radical
      scavenging and beta-carotene/linoleic acid systems. In the first case, the most
      active plant was S. verbenaca (14.30+/-1.42 microg mg(-1)), followed by S.
      virgata (65.70+/-2.12 microg mg(-1)). S. staminae exhibited the weakest
      antioxidant activity in this test system of which IC(50) value is 75.40+/-0.57
      microg mg(-1). In beta-carotene/linoleic acid test system, S. verbenaca extract
      was superior to the other extracts studied (inhibition value is 77.03%+/-0.42).
      Antioxidant activities of BHT, ascorbic acid, curcumin and alpha-tocopherol were
      determined in parallel experiments. Activity of rosmarinic acid was also screened
      for better establishing the relationship between rosmarinic acid level and
      antioxidant activity for the plant extracts. According to the results obtained by
      spectrophotometric analysis and further supported by HPLC, S. verbenaca has the
      highest rosmarinic acid level with a value of 29.30+/-0.24 microg mg(-1). Our
      results showed that the rosmarinic acid and its derivatives are more likely to be
      responsible for most of the observed antioxidant activities of Salvia species.

PMID- 17531472
TI  - Production of (R)-1-(4-Bromo-phenyl)-ethanol by locally isolated Aspergillus
      niger using ram horn peptone.
AB  - Aspergillus niger EBK-9 was isolated from soil sample. This isolate was evaluated
      for production of (R)-1-(4-Bromo-phenyl)-ethanol 2 from 1-(4-Bromo-phenyl)
      ethanone 1. In this work, the production of the 2 was achieved via fermenter.
      Glucose, yeast extract and ram horn peptone as medium in fermenter for growth of
      A. niger was used. A. niger EBK-9 isolate was found to be an effective
      biocatalyst with excellent enantiomeric excess (>99%) and good conversion (100%)
      for the production of the 2 in batch culture. The 8.2 mmol/l product from 10 mmol
      substrate under the optimum conditions could be produced. The yield was
      calculated as 82%. Because of the easy availability of the fungus besides simple
      reaction conditions, this process and medium must be potentially useful for
      production of chiral alcohols.

PMID- 17531473
TI  - Biodiesel production from crude Jatropha curcas L. seed oil with a high content
      of free fatty acids.
AB  - A technique to produce biodiesel from crude Jatropha curcas seed oil (CJCO)
      having high free fatty acids (15%FFA) has been developed. The high FFA level of
      JCJO was reduced to less than 1% by a two-step pretreatment process. The first
      step was carried out with 0.60 w/w methanol-to-oil ratio in the presence of 1%
      w/w H(2)SO(4) as an acid catalyst in 1-h reaction at 50 degrees C. After the
      reaction, the mixture was allowed to settle for 2h and the methanol-water mixture
      separated at the top layer was removed. The second step was transesterified using
      0.24 w/w methanol to oil and 1.4% w/w NaOH to oil as alkaline catalyst to produce
      biodiesel at 65 degrees C. The final yield for methyl esters of fatty acids was
      achieved ca. 90% in 2 h.

PMID- 17531474
TI  - A comparison of kraft, PS, kraft-AQ and kraft-NaBH4 pulps of Brutia pine.
AB  - The aim of this work was to study the effect of adding PS, AQ and NaBH(4) into
      kraft pulping with special attention given to NaBH(4). Kraft, kraft-AQ, PS, and
      kraft-NaBH(4) pulps were produced under the same cooking conditions and the pulps
      produced were compared in terms of pulp and paper properties. Kraft method was
      modified by adding 0.1% AQ, 4% PS and 2% and 4% NaBH(4) and the resultant pulps
      displayed an increase in pulp yield and reduction in both kappa number and
      screening rejects. On the other hand, there observed an increase in both pulp
      yield and kappa number when the kraft was modified to PS method. The benefits of
      NaBH(4) addition into kraft pulping was a significant reduction in kappa number
      and screening rejects and a significant increase in pulp yield. The most notable
      outcome of NaBH(4) was 66.6% increase in pulp brightness when 4% NaBH(4) was
      added into kraft pulping. Of unrefined pulps, unrefined kraft pulp displayed the
      highest strength of pulp, which is described as tear index at a constant tensile
      index. Of refined pulps, kraft-AQ showed the highest pulp strength when refined
      to 6000 and 12,000 revs in PFI mill.

PMID- 17531475
TI  - Greenhouse and field assessment of phytoremediation for petroleum contaminants in
      a riparian zone.
AB  - Greenhouse and field studies were conducted to evaluate the feasibility of
      phytoremediation for clean-up of highly contaminated sediments from Indiana
      Harbor. In the greenhouse study, plant species evaluated were willow (Salix
      exigua), poplar (Populus spp.), eastern gamagrass (Tripsacum dactyloides),
      arrowhead (Sagitaria latifolia), switchgrass (Panicum virgatum), and sedge (Carex
      stricta). Sediments with sedge, switchgrass, and gamagrass had significantly less
      residual total petroleum hydrocarbons (TPH) after one year of growth
      (approximately 70% reduction) than sediments containing willow, poplar, or no
      plants (approximately 20% reduction). Although not all polycyclic aromatic
      hydrocarbons (PAH) had concentration differences due to the presence of plants,
      residual pyrene concentrations in the unvegetated pots were significantly higher
      than in pots containing sedge, switchgrass, arrowhead, and gamagrass. As
      evaluated by TPH dissipation in the upper section of the pots, the sedge,
      switchgrass, and gamagrass treatments had higher TPH degradation than the
      unvegetated, willow and poplar treatments. These trends were similar for soil at
      the bottom of the pots, with the exception that in the switchgrass treatment,
      degradation was not significantly different than in the unvegetated soil. Two
      target contaminants, pyrene and benzo[b]fluoranthene, showed differences in
      degradation between planted and unvegetated treatments. In the field study,
      phytoremediation plant species were eastern gamagrass (T. dactyloides),
      switchgrass (P. virgatum), and sedge (C. stricta). In addition, rhizosphere
      characteristics of arrowhead (S. latifolia) and sedge were assessed. Arrowhead-
      and sedge-impacted soils were found to contain significantly more PAH-degrading
      bacteria than unvegetated soils. However, over the 12-month field study, no
      significant differences in contamination were found between the planted and
      unplanted soils for TPH and PAH concentrations. TPH concentrations near the canal
      were greater than concentrations further from the canal, indicating that the
      canal may have served as a continuous source of contamination during the study.

PMID- 17531476
TI  - Structural analysis of anaerobic granules in a phase separated reactor by
      electron microscopy.
AB  - This paper discusses the microbial community structure of anaerobic granules and
      the effect of phase separation in anaerobic reactor on the characteristics of
      granules. Electron micrographs revealed that the core of anaerobic granular
      sludge consists predominantly of Methanosaeta-like cells, a key microorganism in
      granulation process. Granules in the methanogenic dominant zone of the reactor
      were stable and densely packed with smooth regular surface. On the other hand,
      granules subjected to acidogenic activities were less stable structures with
      broken parts and an irregular fissured surface. Anaerobic granules consisted of a
      vast diversity of species from the outer surface to the core of the granule and
      possessed a multi-layered structure. Viruses in the granules suggests the
      presence of bacteriophage in the granular biomass. These could be responsible for
      destroying cells and weakening the internal structure of granules, and thus
      possibly causing the breaking of granules. The observation of protozoa-like
      microorganism on the exterior zone of granular structure is believed to play an
      important role as bacterial predator and control the growth of bacterial cells.
      The images observed in this study shows that anaerobic granule harbour diverse
      number of microbial species, and act differently in acidogenic and methanogenic
      microbial zones.

PMID- 17531477
TI  - Salmonella reduction in manure by the addition of urea and ammonia.
AB  - Animal manure may contain pathogenic microorganisms and disinfection is suggested
      to avoid reinfection of animal herds and introduction of zoonotic disease into
      the food chain. Ammonia and urea were tested for disinfection of bovine manure
      and Salmonella was found to be rapidly eliminated by the addition of 0.5% aqueous
      ammonia or 2% w/w urea (s). Treatments (2% urea and 0.5% ammonia), temperature (4
      degrees C or 14 degrees C) and combinations of these factors significantly
      affected the inactivation rate. Decimal values (T(90)) were reduced from 8.3 days
      in the control to 2.0 days and 0.4 days at 14 degrees C after the addition of
      urea and ammonia, respectively. At 4 degrees C, the decimal values were reduced
      from 34 to 4.8 and 1.1 days, respectively. Recommended treatments of bovine
      manure based on Monte Carlo simulations are 0.5% ammonia followed by storage for
      one week or 2% urea followed by storage for two weeks at 14 degrees C, one month
      at 4 degrees C. Storage without additives should include at least one summer in
      temperate regions. Enterococci were evaluated as indicators for Salmonella but
      significantly slower decay rate and different behaviour in the material made them
      unsuitable as indicators for Salmonella in manure disinfected by ammonia or urea.
      Free ammonia treatment of Salmonella-contaminated manure disinfects the material
      and raises its fertilizer value.

PMID- 17531478
TI  - Nitrate and phosphate removal by chitosan immobilized Scenedesmus.
AB  - The effect of chitosan immobilization of Scenedesmus spp. cells on its viability,
      growth and nitrate and phosphate uptake was investigated. Scenedesmus sp.
      (strains 1 and 2) and Scenedesmus obliquus immobilized in chitosan beads showed
      high viability after the immobilization process. Immobilized Scenedesmus sp.
      strain 1 had a higher growth rate than its free living counterpart. Nitrate and
      phosphate uptake by immobilized cells of Scenedesmus sp. (strain 1), freely
      suspended cells and blank chitosan beads (without cells) were evaluated.
      Immobilized cells accomplished a 70% nitrate and 94% phosphate removal within 12h
      of incubation while free-living cells removed 20% nitrate and 30% phosphate
      within 36 h of treatment. Blank chitosan beads were responsible for up to 20%
      nitrate and 60% phosphate uptake at the end of the experiment. Chitosan is a
      suitable matrix for immobilization of microalgae, particularly Scenedesmus sp.,
      but this system should be improved before its application for water quality
      control.

PMID- 17531479
TI  - 2-Arylimino-5,6-dihydro-4H-1,3-thiazines as a new class of cannabinoid receptor
      agonists. Part 2: orally bioavailable compounds.
AB  - Structure-activity relationships and efforts to optimize the pharmacokinetic
      profile of a class of 2-arylimino-5,6-dihydro-4H-1,3-thiazines as cannabinoid
      receptor agonists are described. Among the compounds examined, compound 14 showed
      potent affinity and high selectivity for CB2, and compound 23 showed potent
      affinities against CB1 and CB2. These compounds displayed oral bioavailability.

PMID- 17531480
TI  - 2-Cycloalkyl phenoxyacetic acid CRTh2 receptor antagonists.
AB  - High throughput screening identified a phenoxyacetic acid scaffold as a novel
      CRTh2 receptor antagonist chemotype, which could be optimised to furnish a
      compound with functional potency for inhibition of human eosinophil shape change
      and oral bioavailability in the rat.

PMID- 17531481
TI  - Structure-activity studies of phenanthroindolizidine alkaloids as potential
      antitumor agents.
AB  - Five phenanthroindolizidine alkaloids (PA) were chemically synthesized and seven
      were isolated from Tylophora atrofolliculata. To facilitate future drug design of
      phenanthroindolizidine alkaloids as potential antitumor agents, we have explored
      the structure-activity relationships (SAR) of this class of compounds. We
      demonstrated that DCB-3503 and tylophorinidine (PA-7) were among the most active
      compounds against tumor growth both in vitro and in vivo. In the hepatocellular
      carcinoma cell line HepG2, the GI(50)s of DCB-3503 and PA-7 were 35+/-5 nM and
      11+/-5 nM, respectively. DCB-3503 and PA-7 significantly inhibited HepG2 tumor
      growth in nude mice at a dose of 9 mg/kg given by intraperitoneal (ip) injections
      twice a day every third day for a total of four cycles (P<0.05 for DCB-3503 and
      P<0.01 for PA-7). Their potent antitumor activities correlated with their potent
      NF-kappaB-inhibitory effects and their cyclin D1 down-regulatory effects.

PMID- 17531482
TI  - Design and synthesis of 3,3-piperidine hydroxamate analogs as selective TACE
      inhibitors.
AB  - Structure-based methods were used to design beta-sulfone 3,3-piperidine
      hydroxamates as TACE inhibitors with the aim of improving selectivity for TACE
      versus MMP-13. Several compounds in this series were synthesized and evaluated in
      enzymatic and cell-based assays. These analogs exhibit excellent in vitro potency
      against isolated TACE enzyme and show good selectivity for TACE over the related
      metalloproteases MMP-2, -13, and -14.

PMID- 17531483
TI  - Indolinone based phosphoinositide-dependent kinase-1 (PDK1) inhibitors. Part 1:
      design, synthesis and biological activity.
AB  - HTS screening identified 1 with micromolar inhibitory activity against PDK1.
      Optimization of 1 afforded 4i (BX-517) which has single-digit nanomolar activity
      against PDK1 and excellent selectivity against PKA.

PMID- 17531484
TI  - Positional linker effects in haptens for cocaine immunopharmacotherapy.
AB  - Cocaine use remains a serious problem, despite intensive efforts to curb abuse.
      Given the lack of effective pharmacotherapeutics for the treatment of cocaine
      addiction, research groups have targeted immunopharmacotherapy in which the drug
      user's immune system is trained to recognize and remove cocaine prior to entry
      into the central nervous system. Antibody cocaine esterases and simple binders
      have been procured, however, rates and/or affinities still need improvement
      before clinical trials are warranted. Herein, we report the synthesis and testing
      of two new haptens for the procurement of cocaine binding antibodies and cocaine
      esterase catalytic antibodies. Central in the design of these haptens was the
      placement of the linker functionality distal from the anticipated cocaine
      epitopes in an attempt to bury the hapten deep within an antibody combining site
      to gain possible entropic and enthalpic advantages.

PMID- 17531485
TI  - Design and synthesis of 1,2-dithiolane derivatives and evaluation of their
      neuroprotective activity.
AB  - We designed and synthesized new analogues containing 1,2-dithiolane-3-alkyl and
      protected or free catechol moieties connected through heteroaromatic rings such
      as triazole, 1,2,4-oxadiazole, 1,3,4-oxadiazole, tetrazole or thiazole in order
      to explore the influence of the bioisosteric replacement of the amide group on
      the neuroprotective activity of the lipoic acid/dopamine conjugate. Evaluation of
      the activity of the new compounds, using glutamate-challenged hippocampal HT22
      cells, showed that incorporation of heteroaromatic rings in the alkyl-1,2
      dithiolane moieties in conjunction with another antioxidant, in this case
      catechol, may result in strong neuroprotective activity.

PMID- 17531486
TI  - Preparation of 1,3,5-thiadiazine-2-thione derivatives of chitosan and their
      potential antioxidant activity in vitro.
AB  - Three new kinds of 1,3,5-thiadiazine-2-thione derivatives of chitosan with two
      different molecular weight (SATTCS1, SATTCS2, TITTCS1, TITTCS2, CITTCS1 and
      CITTCS2) have been prepared. Their structures were characterized by IR
      spectroscopy. The substitution degree of derivatives calculated by elemental
      analyses was 0.47, 0.42, 0.41, 0.38, 0.41 and 0.36, respectively. The result
      shows that substitution degree of derivatives was higher with lower molecular
      weight. The antioxidant activity was studied using an established system, such as
      hydroxyl radical scavenging, superoxide radical scavenging and reducing power.
      Antioxidant activity of the 1,3,5-thiadiazine-2-thione derivatives of chitosan
      were stronger than that of chitosans and antioxidant activity of low molecular
      weight derivatives were stronger than that of high molecular weight derivatives.
      It is a potential antioxidant in vitro.

PMID- 17531487
TI  - Synthesis, determination of stereochemistry, and evaluation of new bisindole
      alkaloids from the myxomycete Arcyria ferruginea: an approach for Wnt signal
      inhibitor.
AB  - To determine the stereochemistry of dihydroarcyriarubin C (1), new bisindole
      alkaloid isolated from the myxomycete Arcyria ferruginea, cis- (2) and trans
      dihydroarcyriarubin C (3) were synthesized. Comparison of their NMR
      characteristics allowed the trans stereochemistry of the natural product to be
      confirmed. Moreover, the Wnt signal inhibitory activities of 2 and 3 were
      compared with that of arcyriaflavin C (4), which is a natural product containing
      a bond between C-2 and C-2'. The cis-dihydroarcyriarubin C (2) showed moderate
      inhibition of Wnt signal transcription, which suggests that bisindole frameworks
      might be useful as small-molecule Wnt signal inhibitors.

PMID- 17531488
TI  - Discovery of novel prostaglandin analogs of PGE2 as potent and selective EP2 and
      EP4 receptor agonists.
AB  - Analogs of PGE(2) with introduction of diene groups at the omega-side chain have
      been synthesized and evaluated for their binding affinity for EP(2) and EP(4)
      receptors. An optimized analog (compound 9b) showed high potency and selectivity
      for the EP(4) receptor over other known receptors.

PMID- 17531489
TI  - A high-throughput assay for O-GlcNAc transferase detects primary sequence
      preferences in peptide substrates.
AB  - O-GlcNAc transferase (OGT) catalyzes the addition of N-acetylglucosamine (O
      GlcNAc) onto a diverse array of intracellular proteins. Although hundreds of
      proteins are known to be modified by O-GlcNAc, a strict amino acid consensus
      sequence for OGT has not been identified. In this study, we describe the
      development of a high-throughput assay for OGT and use it to profile the
      specificity of the enzyme among a panel of peptide substrates.

PMID- 17531490
TI  - Fever and standard monitoring parameters of ICU patients: a descriptive study.
AB  - OBJECTIVE: To investigate the effect of fever episodes and fever characteristics
      on heart rate, arterial blood pressure and arterial oxygen saturation of
      intensive care unit (ICU) patients. METHODS: This was a prospective study
      conducted in the medical-surgical ICU of General University Hospital of Patras,
      Greece. All patients who were consecutively admitted from October 2005 to
      February 2006 and manifested fever during ICU stay were enrolled. A tympanic
      membrane or an axillary thermometer was used for the measurement of patient
      temperature. Standard monitoring parameters were recorded by nursing personnel at
      1-h intervals. RESULTS: Seventy-five ICU patients manifested fever during the
      study period. Increase of core temperature during fever episodes was followed by
      a significant increase in heart rate (p<0.001) and decreases in arterial blood
      pressure (p<0.001) and arterial oxygen saturation (p=0.002). Alterations of heart
      rate and arterial blood pressure were significantly affected by magnitude of
      fever, while alteration of arterial oxygen saturation was affected by etiology of
      fever. CONCLUSIONS: The present findings confirmed the effect of fever episodes
      on standard monitoring parameters of ICU patients. However, alterations of these
      parameters, although statistically significant, were not clinically important and
      cannot guide antipyretic treatment.

PMID- 17531491
TI  - Enhanced anatomical calibration in human movement analysis.
AB  - The representation of human movement requires knowledge of both movement and
      morphology of bony segments. The determination of subject-specific morphology
      data and their registration with movement data is accomplished through an
      anatomical calibration procedure (calibrated anatomical systems technique: CAST).
      This paper describes a novel approach to this calibration (UP-CAST) which, as
      compared with normally used techniques, achieves better repeatability, a shorter
      application time, and can be effectively performed by non-skilled examiners.
      Instead of the manual location of prominent bony anatomical landmarks, the
      description of which is affected by subjective interpretation, a large number of
      unlabelled points is acquired over prominent parts of the subject's bone, using a
      wand fitted with markers. A digital model of a template-bone is then submitted to
      isomorphic deformation and re-orientation to optimally match the above-mentioned
      points. The locations of anatomical landmarks are automatically made available.
      The UP-CAST was validated considering the femur as a paradigmatic case. Intra-
      and inter-examiner repeatability of the identification of anatomical landmarks
      was assessed both in vivo, using average weight subjects, and on bare bones.
      Accuracy of the identification was assessed using the anatomical landmark
      locations manually located on bare bones as reference. The repeatability of this
      method was markedly higher than that reported in the literature and obtained
      using the conventional palpation (ranges: 0.9-7.6 mm and 13.4-17.9,
      respectively). Accuracy resulted, on average, in a maximal error of 11 mm.
      Results suggest that the principal source of variability resides in the
      discrepancy between subject's and template bone morphology and not in the inter
      examiner differences. The UP-CAST anatomical calibration could be considered a
      promising alternative to conventional calibration contributing to a more
      repeatable 3D human movement analysis.

PMID- 17531492
TI  - Delayed surgical management of a traumatic bilateral cervical facet dislocation
      by an anterior-posterior-anterior approach.
AB  - Delayed diagnosis (more than one month after injury) of a bilateral cervical
      facet dislocation is exceptional, and delayed treatment is different from
      treatment in the acute stage. We describe a neurologically intact 51-year-old
      patient, in whom the diagnosis of bilateral cervical facet dislocation at C5/6
      was made 10 weeks after the trauma. An anterior-posterior-anterior approach was
      performed, with repositioning during the posterior approach, and with anterior
      and posterior C5/6 fixation. The patient remained neurologically intact, and
      radiographic fusion was observed 3, 6, and 12 months postoperatively.
      Additionally, the (English) literature is reviewed and discussed.

PMID- 17531493
TI  - Gait analysis of patients following total knee replacement: a systematic review.
AB  - Gait analysis has been used to objectively measure patients' function following
      total knee replacement (TKR). Whilst the findings of this research may have
      important implications for the understanding of the outcomes of TKR, the
      methodology of existing research appears to be diverse and many of the results
      inconsistent. The objective of this systematic review was to synthesise reported
      findings and to summarise the methods used by researchers in this field. Eleven
      articles published in the medical literature that used gait analysis to compare
      patients following TKR with controls were identified for inclusion in this
      review. Each article was assessed for methodologic quality and data was compared
      across studies through the calculation of effect sizes. Consistently large effect
      sizes showed that patients following TKR walk with less total knee motion during
      gait and with less knee flexion during swing than controls. Kinetic discrepancies
      between patients and controls were also identified. The substantial methodologic
      differences between studies may contribute to the inconsistencies in reported
      findings for many gait outcomes. Future research is needed to determine the
      clinical relevance of these findings.

PMID- 17531494
TI  - Synthesis and evaluation of new 6-hydroximinosteroid analogs as cytotoxic agents.
AB  - Taking into account the structural requirements for cytotoxicity, several new
      hydroximinosteroid derivatives have been prepared and evaluated for their
      cytotoxic activity against A-549, H116, PSN1, and T98G cultured tumor cell lines
      in order to obtain further information on the potential pharmacophoric core of
      this type of compound. The influence of the oxygenated position in the A ring,
      the presence of an additional oxygenated position at C-7 and C-16, and a
      fluorinated position at C-5 were considered in order to study the structure
      activity relationships. The results reveal the importance of oxygenated positions
      in the A ring (e.g., 4,5-epoxide showed an IC50 value against HCT-116 under
      micromolar level) for an increase in cytotoxic activity in this type of compound.
      Furthermore, they showed an important selectivity toward colon tumor line (HCT
      116).

PMID- 17531495
TI  - Antidiabetic copper(II)-picolinate: impact of the first transition metal in the
      metallopicolinate complexes.
AB  - In order to examine the effect of metallopicolinate complexes with first
      transition metals and develop complexes that are more active than an
      insulinomimetic leading compound such as oxovanadium(IV)-picolinate complex,
      VO(pa)2, 10 metallopicolinate complexes were prepared, and their in vitro
      insulinomimetic and in vivo antidiabetic activities were evaluated. The in vitro
      activity was estimated by determining the inhibitory effects of these complexes
      on free fatty acid release from isolated rat adipocytes treated with epinephrine.
      Among the complexes, Cu(pa)2, and Mn(pa)3 exhibited higher activity than their
      respective metal ions and better activity than VO(pa)2. Since Cu(pa)2 was non
      toxic in the cultured rat hepatic M cells, this complex was given streptozotocin
      (STZ)-induced type 1-like diabetic mice by single intraperitoneal injection, and
      found that this complex exhibited a higher hypoglycemic effect than the VO(pa)2
      complex. Based on these results, we propose that Cu(pa)2 may be a potent
      alternative antidiabetic agent.

PMID- 17531496
TI  - Spermatozoal ultrastructure in three species of the genus Uca Leach, 1814
      (Crustacea, Brachyura, Ocypodidae).
AB  - Morphological aspects of spermatozoa in marine animals have been used in recent
      decades as phylogenetic criteria (spermiotaxonomy). This paper presents
      ultrastructural descriptions of the spermatozoa from Uca maracoani, U. thayeri,
      and U. vocator. A small portion of the vas deferens of each species was examined
      under the transmission and scanning electron microscopy. The ultrastructural
      analysis showed that each spermatophore consists of a varying number of
      spermatozoa embedded in a dense fibrillar matrix surrounded by a membrane. The
      spermatozoa of U. maracoani, U. thayeri, and U. vocator are typical of
      brachyurans. The voluminous acrosome is characterized by three different layers.
      The postero-lateral surface of the acrosome is cupped by the reduced cytoplasm,
      and the anterior surface is covered by the operculum. The perforatorium consists
      of coiled, helicoidal membranous tubules and is continuous with the cytoplasm.
      The nucleus is composed by uncondensed chromatin and presents several lateral
      arms distributed over the entire equatorial plane of the cell. The presence of
      the apical button is a well defined character among all species of the genus Uca,
      but in U. thayeri it was not observed. The accessory opercular ring can be found
      in the three studied species, but in distinct development degree. Two centrioles
      were detected in U. thayeri and U. vocator, but only one was found in U.
      maracoani. The presence of centrioles in the mature spermatozoa is the first
      account for the genus Uca upto-date. Considering the ultrastructure of the
      spermatozoa of U. maracoani, U. thayeri, and U. vocator, we suggest that these
      three species partially follow the morphological patterns previously described in
      other Thoracotremata brachyurans. The absence of the apical button in U. thayeri
      spermatozoa may represent an evolutionary novelty in the genus Uca.

PMID- 17531497
TI  - Methodological considerations regarding the use of inorganic 197Hg(II)
      radiotracer to assess mercury methylation potential rates in lake sediment.
AB  - Methodological considerations on the determination of benthic methyl-mercury
      (CH(3)Hg) production potentials were investigated on lake sediment, using (197)Hg
      radiotracer. Three methods to arrest bacterial activity were compared: flash
      freezing, thermal sterilization, and gamma-irradiation. Flash freezing showed
      similar CH(3)Hg recoveries as thermal sterilization, which was both 50% higher
      than the recoveries obtained with gamma-ray irradiation. No additional radiolabel
      was recovered in kill-control samples after an additional 24 or 65 h of
      incubation, suggesting that all treatments were effective at arresting Hg(II)
      methylating bacterial activity, and that the initial recoveries are likely due to
      non-methylated (197)Hg(II) carry-over in the organic extraction and/or
      [(197)Hg]CH(3)Hg produced via abiotic reactions. Two CH(3)Hg extraction methods
      from sediment were compared: (a) direct extraction into toluene after sediment
      leaching with CuSO(4) and HCl and (b) the same extraction with an additional back
      extraction step to thiosulphate. Similar information was obtained with both
      methods, but the low efficiency observed and the extra work associated with the
      back-extraction procedure represent significant disadvantages, even tough the
      direct extraction involves higher Hg(II) carry over.

PMID- 17531498
TI  - The use of high-density concretes in radiotherapy treatment room design.
AB  - With the modernization of radiotherapic centers, medical linear accelerators are
      largely replacing (60)Co teletherapy units. In many cases, the same vault housing
      the (60)Co teletherapy unit is reused for the linear accelerator and, when space
      is at a premium, high-density concrete (3.0-5.0 g/cm(3)) is employed to provide
      shielding against the primary, scatter and leakage radiation. This work presents
      a study based on Monte Carlo simulations of transmission of some clinical photon
      spectra (of 4-10 MV accelerators) through some types of high-density concretes,
      normally used in the construction of radiotherapy bunkers. From the simulations,
      the initial and subsequent tenth-value layers (TVL) for these materials, taking
      into account realistic clinical photon spectra, are presented, for primary
      radiation.

PMID- 17531499
TI  - Separation of no-carrier-added 66,67Ga produced in heavy ion-induced cobalt
      target using alginate biopolymers.
AB  - Heavy ion activation of natural cobalt foil with 84MeV (12)C results in the
      formation of no-carrier-added (nca) (66,67)As radionuclides, along with their
      corresponding decay products, (66,67)Ge and (66,67)Ga, in the matrix. Because
      arsenic and germanium radionuclides are short-lived, after a cooling period of
      10h only nca gallium radionuclides remain in the matrix. We attempted to separate
      the nca gallium radionuclides from the target matrix cobalt by biopolymeric
      calcium alginate (CA) and Fe-doped calcium alginate (Fe-CA) beads. A complete
      separation has been achieved by adsorbing (66,67)Ga and a lesser amount of bulk
      cobalt at pH 3 on Fe-CA beads, followed by desorbing cobalt from the beads with
      0.4M NaNO(2).

PMID- 17531500
TI  - Targeted tandem mass spectrometry for high-throughput comparative proteomics
      employing NanoLC-FTICR MS with external ion dissociation.
AB  - Targeted tandem mass spectrometry (MS/MS) is an attractive proteomic approach
      that allows selective identification of peptides exhibiting abundance
      differences, e.g., between culture conditions and/or diseased states. Herein, we
      report on a targeted LC-MS/MS capability realized with a hybrid quadrupole-7
      tesla Fourier transform ion cyclotron resonance (FTICR) mass spectrometer that
      provides data-dependent ion selection, accumulation, and dissociation external to
      the ICR trap, and a control software that directs intelligent MS/MS target
      selection based on LC elution time and m/z ratio. We show that the continuous on
      the-fly alignment of the LC elution time during the targeted LC-MS/MS experiment,
      combined with the high mass resolution of FTICR MS, is crucial for accurate
      selection of targets, whereas high mass measurement accuracy MS/MS data
      facilitate unambiguous peptide identifications. Identification of a subset of
      differentially abundant proteins from Shewanella oneidensis grown under suboxic
      versus aerobic conditions demonstrates the feasibility of such approach.

PMID- 17531501
TI  - Backbone cleavages and sequential loss of carbon monoxide and ammonia from
      protonated AGG: a combined tandem mass spectrometry, isotope labeling, and
      theoretical study.
AB  - The fragmentation characteristics of protonated alanylglycylglycine, [AGG +
      H](+), were investigated by tandem mass spectrometry in MALDI-TOF/TOF, ion trap,
      and hybrid sector instruments. b(2) is the most abundant fragment ion in MALDI
      TOF/TOF, ion trap, and hybrid sector metastable ion (MI) experiments, while y(2)
      is slightly more abundant than b(2) in collision activated dissociation (CAD)
      performed in the sector instrument. The A-G amide bond is cleaved on the a(1)
      y(2) pathway resulting in a proton-bound dimer of GG and MeCH=NH. Depending on
      the fragmentation conditions employed, this dimer can then (1) be detected as
      [AGG + H - CO](+), (2) dissociate to produce y(2) ions, [GG + H](+), (3)
      dissociate to produce a(1) ions, [MeCH=NH + H](+), or (4) rearrange to expel
      NH(3) forming a [AGG + H - CO - NH(3)](+) ion. The activation method and the
      experimental timescale employed largely dictate which of, and to what extent,
      these processes occur. These effects are qualitatively rationalized with the help
      of quantum chemical and RRKM calculations. Two mechanisms for formation of the
      [AGG + H - CO - NH(3)](+) ion were evaluated through nitrogen-15 labeling
      experiments and quantum chemical calculations. A mechanism involving
      intermolecular nucleophilic attack and association of the GG and imine fragments
      followed by ammonia loss was found to be more energetically favorable than
      expulsion of ammonia in an S(N)2-type reaction.

PMID- 17531502
TI  - A refined comorbidity measurement algorithm for claims-based studies of breast,
      prostate, colorectal, and lung cancer patients.
AB  - PURPOSE: We evaluated (i) how combining comorbid conditions identified from
      Medicare inpatient or physician claims into a single comorbidity index compared
      with three other comorbidity indices and (ii) the need for comorbid condition
      weights that are specific to different cancer sites. METHODS: This observational
      study used the SEER-Medicare linked database, from which four cohorts of cancer
      patients were derived: breast (n = 26,377), prostate (n = 53,503), colorectal (n
      = 26,460), and lung (n = 33,975). We calculated two established (Charlson; NCI)
      and two new (NCI Combined; Uniform Weights) comorbidity indices, and used Cox
      proportional hazards models to assess their predictive ability. We also used a
      pooled dataset to examine the inclusion of cancer site-specific condition
      weights. RESULTS: The four comorbidity indices all significantly predicted
      mortality, but the NCI and new NCI Combined indices showed the greatest
      contribution to model fit. The new NCI Combined index is simpler to use and
      statistically more efficient than the NCI index. Modeling further demonstrated
      the utility of cancer site-specific weights. CONCLUSIONS: Our results support the
      need for cancer site-specific comorbidity measures that employ empirically
      derived condition weights. The new NCI Combined index is a refined, easier to
      implement comorbidity measurement algorithm appropriate for investigators using
      administrative claims databases to study four commonly-occurring cancers.

PMID- 17531503
TI  - Modeling smoking history: a comparison of different approaches in the MARS study
      on age-related maculopathy.
AB  - PURPOSE: Smoking is an established risk factor for the development of age-related
      maculopathy (ARM), and its end stage, age-related macular degeneration (AMD). We
      evaluated the benefit of various smoking-related variables in modeling the
      association of smoking with ARM and AMD in a mixed sample of current, former, and
      never smokers. METHODS: This was a cross-sectional study in participants of the
      Muensteraner Altern- und Retina-Studie (MARS). Participants were classified
      according to the Rotterdam classification system as healthy, or having ARM or
      AMD. Using multinomial logistic regression techniques, the association with
      number of cigarettes, years of smoking, pack-years and time since cessation in
      former smokers were evaluated. RESULTS: Mean age of the 982 participants (58.6%
      females) was 70.9 +/- 5.5 years. ARM was present in 483 (49.2%) and AMD in 285
      (29.0%) individuals. The adjusted prevalence odds ratio (OR) in current smokers
      versus never smokers was 2.61 (95% confidence interval [CI] 1.34-5.09) for ARM
      and 3.94 (95% CI 1.91-8.14) for AMD. This effect decreased in former smokers with
      an OR = 0.55 (95% CI 0.33-0.99) per log-transformed time since smoking cessation
      for ARM and an OR = 0.52 (95% CI 0.30-0.90) for AMD. CONCLUSIONS: By including a
      variable for time since smoking cessation, we were able to handle current,
      former, and never smokers in one model that estimates the association of smoking
      with ARM or AMD. Logarithmical transformation of the time since smoking cessation
      seemed to increase the model fit and to reflect a non-linear protective effect of
      smoking cessation on the onset of ARM and AMD in former smokers.

PMID- 17531504
TI  - Participation in research studies: factors associated with failing to meet
      minority recruitment goals.
AB  - PURPOSE: To determine the recruitment goals that investigators set for
      racial/ethnic minorities and the factors associated with failure to meet those
      goals. METHODS: Four hundred forty principal investigators (PIs) conducting
      clinical research funded by the National Heart, Lung, and Blood Institute (NHLBI)
      in 2001 completed a mailed survey providing their minority recruitment goals and
      enrollment data for their most recent NHLBI-funded study. RESULTS: Ninety-two
      percent of PIs set goals for African Americans, 68% for Hispanics, 55% for Asian
      Americans, 35% for Native Hawaiians/Pacific Islanders, and 23% of PIs set
      recruitment goals for American Indians/Native Alaskans. Among those PIs who did
      set minority recruitment goals, the mean goal for the recruitment of African
      Americans was 31%, 16% for Hispanics, and 9% for Asian Americans. Twenty-seven
      percent of PIs failed to meet their recruitment goals for African Americans, 23%
      for Asian Americans, and 23% for Hispanics. After adjusting for multiple
      investigator and trial characteristics, the type of study (odds ratio [OR] 1.8;
      95% confidence interval [CI] 1.2, 3.4 for observational vs. phase III trial)
      completion of study enrollment (OR 2.0; 95% CI 1.2, 3.4), and PI identification
      of a larger number of major barriers to participation (OR 1.8; 95% CI 1.1, 3.0)
      were all associated with failure to meet recruitment goals for African Americans.
      However, no factors were consistently associated with failure to meet recruitment
      goals across different racial/ethnic groups. CONCLUSIONS: Investigators often do
      not set recruitment goals for some racial/ethnic groups. Factors associated with
      failure to meet recruitment goals vary in the recruitment of different minority
      groups.

PMID- 17531505
TI  - Weighting condom use data to account for nonignorable cluster size.
AB  - PURPOSE: We examined the impact of weighting the generalized estimating equation
      (GEE) by the inverse of the number of sex acts on the magnitude of association
      for factors predictive of recent condom use. METHODS: Data were analyzed from a
      cross-sectional survey on condom use reported during vaginal intercourse during
      the past year among male students attending two Georgia universities. The usual
      GEE model was fit to the data predicting the binary act-specific response
      indicating whether a condom was used. A second cluster-weighted GEE model (i.e.,
      weighting the GEE score equation by the inverse of the number of sex acts) was
      also fit to predict condom use. RESULTS: Study participants who engaged in a
      greater frequency of sex acts were less likely to report condom use, resulting in
      nonignorable cluster-size data. The GEE analysis weighted by sex act (usual GEE)
      and the GEE analysis weighted by study subject (cluster-weighted GEE) produced
      different estimates of the association between the covariates and condom use in
      last year. For example, the cluster-weighted GEE analysis resulted in a
      marginally significant relationship between age and condom use (odds ratio of
      0.49 with 95% confidence interval (0.23-1.03) for older versus younger
      participants) versus a nonsignificant relationship with the usual GEE model (odds
      ratio of 0.67 with a 95% confidence interval of 0.28-1.60). CONCLUSIONS: The two
      ways of weighting the GEE score equation, by the sex act or by the respondent,
      may produce different results and a different interpretation of the parameters in
      the presence of nonignorable cluster size.

PMID- 17531506
TI  - Social avoidance and long-term risk for cardiovascular disease death in healthy
      men: the Western Electric study.
AB  - PURPOSE: Although personality traits may contribute to risk for cardiovascular
      disease (CVD), inconsistent findings have prompted efforts to refine their
      measurement to include only the hostile and aggressive components. Data are
      sparse on the "social avoidance" (SA) subscale that measures more indirectly
      negative traits such as shyness. Thus, we sought to examine the association
      between SA and CVD, coronary heart disease (CHD), and non-CVD death. METHODS: A
      total of 2107 men (ages 40-55 years) free of baseline CVD were enrolled in 1957
      in the Western Electric Study. SA was measured at study entry using the four-item
      subscale of the Cook-Medley hostility scale to divide the cohort into four groups
      according to the degree of social avoidance. CHD mortality, CVD mortality, and
      non-CVD mortality were determined by death certificate. RESULTS: After 30 years
      of follow-up, SA was associated with CVD mortality for the highest vs. the lowest
      SA group in age-adjusted models (hazard ratio 1.39; 95% confidence interval [95%
      CI] 1.04-1.84) and after adjustment for traditional CVD risk factors (hazard
      ratio 1.49; 95% CI 1.12-2.00). After further adjustment for measures of
      hostility, the findings were similar. Findings for CHD mortality were similar.
      However, there was no significant association between SA and non-CVD mortality.
      CONCLUSIONS: Social avoidance is associated with CVD mortality but not with non
      CVD mortality in middle-aged men. These findings suggest the hypothesis that
      social avoidance might promote CVD through physiologic, non-behavioral
      mechanisms.

PMID- 17531507
TI  - Phylogenetic analysis of chloroplast DNA matK gene and ITS of nrDNA sequences
      reveals polyphyly of the genus Sonchus and new relationships among the subtribe
      Sonchinae (Asteraceae: Cichorieae).
AB  - Phylogenetic relationships among genera of the subtribes Sonchinae (11 genera and
      ca. 130 species) and Dendroseridinae (2 genera and 12 species) sensu Bremer were
      assessed with ITS and matK gene sequences. The Sonchinae is strongly supported as
      paraphyletic, and subtribal rank of Dendroseridinae is poorly supported. This
      study re-delimits Sonchinae, which now includes 14 genera and ca. 146 species.
      Two genera, Reichardia and Launaea, diverge first, followed by a major radiation
      of the remaining species, including Dendroseris and Thamnoseris. The monotypic
      Aetheorhiza is more closely related to Sonchus than to Launaea. Sonchus is highly
      polyphyletic, occurring across nearly all clades of the trees. It is highly
      probable that several Pacific and Atlantic island endemics evolved within the
      Sonchus group. Polyploidization processes appear to have played an important role
      in evolutionary differentiation and speciation in Sonchus, especially in subgenus
      Sonchus. This study identifies 10 major clades within the Sonchinae, and
      emphasizes the need to re-delimit and re-circumscribe Sonchus and the Sonchinae.

PMID- 17531508
TI  - Phylogenetic relationships in genus Niviventer (Rodentia: Muridae) in China
      inferred from complete mitochondrial cytochrome b gene.
AB  - Chinese species of the genus Niviventer, predominantly distributed in the
      southeastern Tibetan Plateau and in Taiwan, are a diverse group and have not yet
      received a thorough molecular phylogenetic analysis. Here, we reconstructed the
      phylogenetic relationships of 32 specimens representing nine Chinese species of
      Niviventer, based on sequences of the complete mitochondrial cytochrome b gene.
      Maximum parsimony, maximum likelihood and Bayesian analysis resulted in three
      consistent trees, each supported by high bootstrap values. The results showed
      that the Niviventer species included here are monophyletic. The nine species were
      classified into three distinct clades: clade A with Niviventer brahma, N.
      confucianus, N. coxingi, N. culturatus, N. eha and N. fulvescens; clade B with N.
      andersoni and N. excelsior; clade C with N. cremoriventer. Our results also
      suggested that N. culturatus should be a valid species rather than a subspecies
      of N. confucianus. Divergence times among species were calibrated according to
      the middle-late Pleistocene (1.2-0.13 Mya) fossil records of N. confucianus. The
      results demonstrated that the first radiation event of the genus Niviventer
      occurred in early Pleistocene (about 1.66 Mya), followed by the divergence of
      clades A and B at about 1.46 Mya. Most of the extant Niviventer species appeared
      during early to middle Pleistocene (about 1.29-0.67 Mya). These divergence times
      are coincidental with the last uplift events of the Tibetan Plateau, Kun-Huang
      movement, Pleistocene glaciations and the vicariant formation of Taiwan Strait.
      Consequently geographical events and Pleistocene glaciations have played a great
      role in the diversification of Niviventer.

PMID- 17531509
TI  - Genetic diversity and spatial correlation patterns unravel the biogeographical
      history of the European sweet vernal grasses (Anthoxanthum L., Poaceae).
AB  - Different processes have contributed to shaping the present distribution of the
      European biotas. Up to three different tertiary- to quaternary-time-scale
      evolutionary scenarios have been proposed to interpret the divergence and genetic
      structuring of plant species in Europe. In the present study, the Amplified
      Fragment Length Polymorphisms technique has been used to unravel the species and
      regional phylogeography of the European sweet vernal grasses (Anthoxanthum L.
      Poaceae). Forty-six populations belonging to all seven European species of
      Anthoxanthum and covering a broad geographical and ecological range were
      selected. Different phylogeography and population genetics diversity and
      structure estimates indicated a clear divergence of old Messinian Mediterranean
      lineages, followed by a pre-Pliocene split between Mediterranean annuals and
      Eurosiberian perennials and a more recent Pleistocene differentiation of Arctic
      Alpine, Atlantic and Submediterranean diploid to polyploid landraces. Regional
      and population correlation tests between geographical and genetic distances
      allowed to postulate distinct pre- and post-glacial colonization pathways across
      Europe for the taxa of this widespread genus.

PMID- 17531510
TI  - The anatomy of the proximal ulna.
AB  - The posterior border of the ulna is the most important bony landmark for all
      dorsal surgical approaches and the guideline for open reduction, internal
      fixation of displaced comminuted fractures of the proximal ulna. We examined 74
      cadaveric specimens to evaluate the anatomy of the proximal ulna, especially the
      course of the posterior border, the point of varus angulation, the width of the
      shaft, and the relationship of the posterior border to the interosseous and
      anterior ones. In 63 specimens, the mean point of varus angulation was 85.4 mm,
      and the average angulation angle was 17.7 degrees. In 11 specimens, the posterior
      border was either radially bowed or the bow was poorly defined and not localized
      to a specific area along the length of the bone. In conclusion, the variations of
      the proximal ulna have to be considered if dorsal plates and intramedullary
      screws are used.

PMID- 17531511
TI  - Arthroscopic revision of Bankart repair.
AB  - The success of revision surgery for failed Bankart repair is not well known. This
      purpose of this study was to report the success rates achieved using arthroscopic
      techniques to revise failed Bankart repairs. Twelve arthroscopic revision Bankart
      repairs were performed on patients with recurrent unidirectional shoulder
      instability after open or arthroscopic Bankart repair. Follow-up was available on
      11 of the 12 patients at a mean of 34.4 months (range, 25-56 months). The
      surgical findings, possible modes of failure, shoulder scores (Rowe score,
      University of California Los Angeles [UCLA], Simple Shoulder Test), and clinical
      outcome were evaluated. Various modes of failure were recognized during revision
      arthroscopic Bankart repairs. Good-to-excellent results were obtained in 8
      patients (73%) undergoing revision stabilization according to Rowe and UCLA
      scoring. A subluxation or dislocation event occurred in 3 (27%) of the 11
      patients at a mean of 8.7 months (range, 6-12 months) postoperatively.
      Arthroscopic revision Bankart repairs are technically challenging procedures but
      can be used to achieve stable, pain-free, functional shoulders with return to
      prior sport. Owing to limited follow-up and the small number of patients in this
      study, we were unable to conclude any pattern of failure or selection criteria
      for this procedure.

PMID- 17531512
TI  - Polyethylene insert exchange for wear after total shoulder arthroplasty.
AB  - Virtually no information is available in the literature to guide clinical
      decision-making in regard to modular polyethylene exchange with metal-backed
      glenoid components in total shoulder arthroplasty for the indication of
      polyethylene wear. This level IV study reports our experience with exchange of
      the modular polyethylene glenoid component during revision total shoulder
      arthroplasty. We retrospectively identified 12 shoulders in 11 patients who
      underwent exchange of the modular polyethylene glenoid component during revision
      arthroplasty. The primary reason for revision arthroplasty with polyethylene
      exchange was wear-through or displacement of the polyethylene portion of the
      glenoid component, but rotator cuff tearing and instability often coexisted. The
      average follow-up from time of revision to latest evaluation or repeat revision
      arthroplasty was 68 months. Preoperative pain was a mean of 4.5 (range, 4-5), and
      postoperative pain was a mean of 2.6 (range, 1-5). Preoperative average active
      forward elevation was 93 degrees, and external rotation was 51 degrees.
      Postoperative active forward elevation was 89 degrees, and external rotation was
      64 degrees. Average patient satisfaction was rated as the same. According to the
      modified Neer rating system, 4 shoulders (33%) had a satisfactory result, and 8
      (62%) had an unsatisfactory result. Polyethylene exchange of glenoid component
      after total shoulder arthroplasty can be an effective treatment option in
      patients who do not have coexistent rotator cuff tear or instability. For most,
      instability, rotator cuff tear, and glenoid wear occur together, and this is a
      challenging problem to treat successfully.

PMID- 17531513
TI  - Nonoperative management of idiopathic adhesive capsulitis.
AB  - Adhesive capsulitis of the shoulder is a common disorder, yet literature on its
      natural history is limited. This study examined patient characteristics,
      treatment patterns, and response to treatment of the disease in a large series of
      patients with this condition. Charts of 234 patients treated at our institution
      for adhesive capsulitis were reviewed retrospectively. The end points for the
      study were defined as resolution of symptoms with nonoperative treatment or
      operative treatment. A total of 105 shoulders in 98 patients were identified with
      follow-up to end point. Of these, 89.5% resolved with nonoperative treatment,
      including 17 (89.5%) of 19 diabetic shoulders. The average age of patients who
      went on to surgery was 51 years, whereas the average age of patients treated
      nonoperatively was significantly higher at 56. No significant difference was
      found for success of nonoperative treatment versus operative treatment or patient
      gender. All patients received nonsteroidal antiinflammatory medications, 52.4%
      received physical therapy without cortisone injection, and 37.1% received therapy
      with at least 1 corticosteroid injection. Duration of treatment in successfully
      nonoperatively treated patients averaged 3.8 +/- 3.6 months. Patients who
      required surgery were treated with an average of 12.4 +/- 12.1 months of
      nonoperative treatment. Initial forward elevation averaged 118 degrees +/- 22
      degrees with average forward elevation at resolution of 164 degrees +/- 17
      degrees. External rotation improved from an average of 26 degrees +/- 16 degrees
      pretreatment to 59 degrees +/- 18 degrees posttreatment. With supervised
      treatment, most patients with adhesive capsulitis will experience resolution with
      nonoperative measures in a relatively short period. Only a small percentage of
      patients eventually require operative treatment.

PMID- 17531514
TI  - Pulmonary embolism after operative treatment of proximal humeral fractures.
AB  - There have been multiple studies on the prevalence of pulmonary embolism, the
      probability of death from a pulmonary embolism, and the risk factors for the
      development of pulmonary embolism after lower extremity and pelvic trauma.
      However, there is no information on the risk of pulmonary embolism after the
      surgical management of proximal humeral fractures. A review of 137 consecutive
      patients who underwent operative treatment for acute, isolated proximal humeral
      fractures at our institution between January 1, 1998, and December 31, 2003, was
      performed to identify all who sustained a pulmonary embolism. Postoperatively, 7
      patients sustained a pulmonary embolism that was confirmed by computed
      tomography. Of these, 4 had been treated with a hemiarthroplasty and 3 had
      undergone open reduction-internal fixation. The overall incidence of pulmonary
      embolism in this series was 5.1%. None of the patients sustained a fatal
      pulmonary embolus. These data suggest that the rate of pulmonary embolism after
      operative treatment of proximal humeral fractures is not low. This study raises
      the question of whether prophylactic anticoagulation is needed after routine
      proximal humeral repair.

PMID- 17531515
TI  - Does taste or odor activate the same brain networks after retrieval of taste
      potentiated odor aversion?
AB  - When simultaneous presentation of odor and taste cues precedes illness, rats
      acquire robust aversion to both conditioned stimuli. Such a phenomenon referred
      to as taste-potentiated odor aversion (TPOA) requires information processing from
      two sensory modalities. Whether similar or different brain networks are activated
      when TPOA memory is retrieved by either the odor or the taste presentation
      remains an unsolved question. By means of Fos mapping, we investigated the
      neuronal substrate underlying TPOA retrieval elicited by either the odor or the
      taste conditioned stimulus. Whatever the sensory modality used to reactivate TPOA
      memory, a significant change in Fos expression was observed in the hippocampus,
      the basolateral nucleus of amygdala and the medial and the orbito-frontal
      cortices. Moreover, only the odor presentation elicited a significantly higher
      Fos immunoreactivity in the piriform cortex, the entorhinal cortex and the
      insular cortex. Lastly, according to the stimulus tested to induce TPOA
      retrieval, the BLA was differentially activated and a higher Fos expression was
      induced by the odor than by the taste in this nucleus. The present study
      indicates that even if they share some brain regions, the cerebral patterns
      induced by either the odor or the taste are different. Data are discussed in view
      of the relevance of each conditioned stimulus to reactivate TPOA memory and of
      the involvement of the different labeled brain areas in information processing
      and TPOA retrieval.

PMID- 17531516
TI  - Molecular characterization and antimicrobial susceptibilities of extra-intestinal
      Clostridium difficile isolates.
AB  - Amongst 25 extra-intestinal clinical isolates of Clostridium difficile, A(+)B(+)
      (72%) and A(-)B(+) (4%) toxigenic phenotypes, as well as the non-toxigenic
      phenotype (A(-)B(-)) (24%), were identified. The A(-)B(-) isolates did not
      express toxin, yet carried part of the tcdA and tcdB gene and are of a previously
      unreported toxinotype. Six A(+)B(+) isolates also carried binary toxin genes.
      Resistance to erythromycin (20%), clindamycin (48%), tetracycline (16%),
      moxifloxacin (16%) and imipenem (11%) occurred but with no apparent correlation
      to phenotype. None of the strains was resistant to vancomycin or metronidazole.
      Imipenem-resistance decreased by EDTA, but susceptibility to meropenem suggests
      the presence of an imipenem specific metalloenzyme.

PMID- 17531517
TI  - Modelling the restoration of wild-type dynamic behaviour in DeltaF508-CFTR NBD1
      by 8-cyclopentyl-1,3-dipropylxanthine.
AB  - Cystic fibrosis (CF) is the most frequently occurring severe, genetic disease in
      western populations with an incidence as high as 1 in 2500. The principal
      biochemical defect in CF is a mutation in a membrane transport protein, namely
      the cystic fibrosis transmembrane conductance regulator (CFTR), which is
      responsible for the conductance of chloride ions across cell membranes. In 70% of
      cases a single mutation in CFTR, namely the deletion of amino acid 508 (called
      DeltaF508) is sufficient to cause severe disease. This mutation manifests as a
      failure of the protein to be effectively targeted to the membrane. Recently, it
      has been shown that small molecule drug therapy can restore the membrane
      targeting of DeltaF508-CFTR, where the mutant channel functions adequately. We
      have created models of the first nucleotide-binding domain (NBD1) region (which
      houses the proposed binding site of these restorative drugs) of the wild-type and
      mutant forms of human CFTR. We have simulated the dynamical behaviour of these
      proteins in the presence of drugs that restore trafficking of the protein. Our
      results indicate that there are particular modes of dynamic motion that are
      distinguishable between wild-type and mutant CFTR. These regions of motion are
      localized in the regions of the DeltaF508 mutation and the drug-binding regions.
      The simulations of drug binding indicate that wild-type dynamic motions are
      restored in these regions. We conclude therefore that these drugs are able to
      alter the dynamic properties of DeltaF508-CFTR such that the drug-bound mutant
      protein more closely resembles the wild-type protein dynamic behaviour, and hence
      we hypothesize that it is this that allows for correct targeting to the membrane.

PMID- 17531518
TI  - [Osteoid osteoma of the lunate: case report].
AB  - The Osteoid Osteome is a benign tumour which affects the young subjects and is
      electively located on the level of the long bones. We report a hyperalgic form of
      the lunatum in a young student with which surgical excision with bone-graft
      allowed the cure.

PMID- 17531519
TI  - [The clinical value of ultrasound for endometrial receptivity assessment in
      Assisted Reproductive Techniques (ART) procedures].
AB  - The search for improving the implantation rate of embryo transfer resulted in
      defining embryo quality standards, making it possible to select embryos with the
      best potential of implantation. A favorable uterine environment is the other
      primordial factor of successful embryo implantation. In addition to the
      endometrial thickness, which is a traditional criterion, many sonographic
      parameters likely to reflect the uterine receptivity state were studied. Lots of
      studies dealt with their predictive value and practical interest.

PMID- 17531520
TI  - [Obstetrical and neonatal outcomes of gestational diabetes mellitus at Reunion
      Island (France)].
AB  - OBJECTIVE: To assess maternal and fetal outcomes in patients with gestational
      diabetes mellitus. PATIENTS AND METHODS: A retrospective study was conducted at
      the Sud-Reunion Hospital's maternity (French overseas department located in the
      Indian Ocean), during the period from January 1, 2001, through December 31, 2004.
      During this period, 1172 pregnant women presenting gestational diabetes mellitus
      were compared with 1172 non-diabetic controls matched on the basis of age,
      parity. Student t test, Pearson chi-square test and logistic regression model
      were used for statistical analysis. RESULTS: Gestational diabetes mellitus
      complicates about 7.5% of pregnancies in Reunion Island. Its occurrence was
      associated with a significantly increased prevalence of pre-pregnancy obesity (27
      versus 9.4%) and chronic hypertension (5.3 versus 3.3%). The prevalence of
      preeclampsia and obstetrical vascular disorders were not different between the
      two groups, respectively 2.2 versus 2.7% (P=0.43) and 6.2 versus 4.4% (P=0.06).
      The rate of caesarean sections and inductions of labour was increased in the
      study group. The term of delivery was inferior in the study group, consecutive to
      increased rate of labour induction at 38 week-gestation. Macrosomia and large for
      gestational age (LGA) newborns rate were significantly higher in the study group,
      respectively 8.9 versus 4.2% and 22.5 versus 10.1% (P<0.001) but the rate of
      admission into neonatal unit was not significantly different. DISCUSSION AND
      CONCLUSION: Active management of gestational diabetes mellitus is associated with
      low maternal and perinatal morbidity. While age and parity are controlled by the
      study design, the prevalence of preeclampsia and gestational hypertension are not
      increased in women presenting gestational diabetes mellitus.

PMID- 17531521
TI  - The influence of ventilation tube design on the magnitude of stress imposed at
      the implant/tympanic membrane interface.
AB  - The design of ventilation tubes or grommets is thought to have a considerable
      influence on their performance. A computational model (finite element method) was
      used to investigate the significance of four design parameters of a commonly used
      design of ventilation tube. The design parameters were: the length of the shaft,
      the diameter of the flanges, the thickness of the flanges, and the material type.
      A statistical analysis technique, known as a factorial analysis of variance, was
      used to examine the importance of the four design parameters on the dynamical
      behaviour of the middle ear with the implant in situ and on the magnitude of
      stress induced at the implant/tympanic membrane interface. We predicted that the
      ventilation tube alters the frequency response of the middle ear; specifically
      the shaft length and the thickness of the flanges were found to have a
      significant effect upon the vibratory pattern at the umbo. A reduced length of
      tube and an increased size of flange were also found to be significant for
      minimising membrane stress (both with P<0.001). Thus, design parameters of
      critical influence on optimising performance were identified.

PMID- 17531522
TI  - Superoxide anion: oncogenic reactive oxygen species?
AB  - Recent evidence linking intracellular reactive oxygen species to cell survival
      and/or proliferation signals has resulted in a paradigm shift from the age-old
      dogma implicating reactive oxygen species exclusively in cell damage and death.
      It is now accepted that reactive oxygen species play important roles in normal
      physiological states and that depending on the species involved the effect could
      be highly varied. In this regard, the effects of the two major reactive oxygen
      species, superoxide and hydrogen peroxide have been extensively studied. During
      normal cell growth a tight balance between the two species is kept under check by
      the cells' anti-oxidant defense systems. Deficiency or defect in this defense
      armory is invariably associated with neoplasia, thus rendering the intracellular
      redox status in a state of imbalance and generating a "pro-oxidant" milieu. A
      variety of model systems have underscored the relationship between a pro-oxidant
      state and cancer promotion and progression. In this review, we present evidence
      to support the hypothesis that the effect of intracellular reactive oxygen
      species on oncogenesis is dependent on the ratio of intracellular superoxide to
      hydrogen peroxide in that a predominant increase in superoxide supports cell
      survival and promotes oncogenesis whereas a tilt in favor of hydrogen peroxide
      prevents carcinogenesis by facilitating cell death signaling.

PMID- 17531523
TI  - Molecular insight in cancer treatment and prevention.
AB  - This article explores the impact of new insights in the biology of cancer on the
      treatment and the prevention of this disease. There are two types of targeted
      cancer treatment, afforded by the molecular profile of cancer. One concerns the
      use of agents targeted on a specific component of the cancer cells (e.g., CD20 in
      lymphoma) or on a specific survival function of the cancer cell (growth-factor
      receptor interaction; transduction cascade). The other concerns the recognition
      of tumors that are more or less likely to benefit from cytotoxic chemotherapy
      according to their genomic or proteomic profile. Cancer prevention may benefit
      from new molecular insight in cancer biology as these processes allow early
      diagnosis of cancer, identification of patients at risk for cancer, and may
      provide intermediate markers for chemoprevention studies.

PMID- 17531524
TI  - Nerve growth factor and tissue repair remodeling: trkA(NGFR) and p75(NTR), two
      receptors one fate.
AB  - This review deals with the role of nerve growth factor (NGF) in healing process
      as a result of injury. The role of both trkA(NGFR) and p75(NTR) specific NGF
      receptors and their contribution in the complex network of tissue repair process,
      is discussed and highlighted in view of recent findings. In fact, NGF represents
      a significant advance in the treatment of etiologically different ulcers (corneal
      ulcers, pressure ulcers, post-viral infections, chemical burns) and might shorten
      the recovery process. For these diseases, no specific treatment is actually
      available. It is reasonable that apart from NGF and/or neurotrophins a different
      time-course of trkA(NGRF)/p75(NTR) expression, might regulate the final process.
      In summary, these novel findings on the potential pro-healing capacity of NGF
      might open new possibilities for this growth factor in modulating the healing
      processes in several pathological conditions.

PMID- 17531525
TI  - Polymorphisms in base-excision repair and nucleotide-excision repair genes in
      relation to lung cancer risk.
AB  - Polymorphisms in DNA repair genes may be associated with differences in DNA
      repair capacity, thereby influencing the individual susceptibility to smoking
      related cancer. We investigated the association of 10 base-excision and
      nucleotide-excision repair gene polymorphisms (XRCC1 -77 T/C, Arg194Trp,
      Arg280His and Arg399Gln; APE1 Asp148Glu; OGG1 Ser326Cys; XPA -4 G/A; XPC PAT; XPD
      Asp312Asn and Lys751Gln) with lung cancer risk in Caucasians. Genotypes were
      determined by PCR-RFLP and PCR-single base extension assays in 110 lung cancer
      patients and 110 age- and sex-matched controls, and the results were analyzed
      using logistic regression adjusted for relevant covariates. A significant
      association between the APE1 Asp148Glu polymorphism and lung cancer risk was
      found, with adjusted odds ratios (OR) of 3.38 (p=0.001) for the Asp/Glu genotype
      and 2.39 (p=0.038) for the Glu/Glu genotype. Gene-smoking interaction analyses
      revealed a statistically significant interaction between cumulative cigarette
      smoking and the XRCC1 Arg399Gln and XPD Lys751Gln polymorphisms: these
      polymorphisms were significantly associated with lung cancer in nonsmokers and
      light smokers (<25 PY; OR=4.92, p=0.021 for XRCC1 399 Gln/Gln; OR=3.62, p=0.049
      for XPD 751 Gln/Gln), but not in heavy smokers (> or =25 PY; OR=0.68, p=0.566 for
      XRCC1 399 Gln/Gln; OR=0.46, p=0.295 for XPD 751 Gln/Gln). Both the XRCC1
      Arg194Trp and Arg280His as well as the OGG1 Ser326Cys heterozygous genotypes were
      associated with a significantly reduced risk for lung cancer (OR=0.32, p=0.024;
      OR=0.25, p=0.028; OR=0.51, p=0.033, respectively). No associations with lung
      cancer risk were found for the XRCC1 -77 T/C, the XPA -4 G/A and the XPC PAT
      polymorphisms. In conclusion, the APE1 Asp148Glu polymorphism is highly
      predictive for lung cancer, and cumulative cigarette smoking modifies the
      associations between the XRCC1 Arg399Gln and the XPD Lys751Gln polymorphisms and
      lung cancer risk.

PMID- 17531526
TI  - Development of a flow-through optosensor for determination of Co(II).
AB  - A flow-through optical fibre chemical sensor for the determination of Co(II) at
      trace level using immobilised 2-(4-pyridylazo)resorcinol (PAR) as the reagent
      phase is proposed. PAR is physically adsorbed onto XAD-7. This method provided a
      great sensitivity and simplicity with wide linear response range from 1x10(-2) to
      1x10(3)ppm and detection limit of 20ppb. This method also showed a reproducible
      result with relative standard deviation (R.S.D.) of 1.78% and response time of
      approximately 5min. The response towards Co(II) was also reversible using
      acidified KCl as the regenerating solution. Interference studies showed that
      Cr(III) significantly interfered during the determination. Excellent agreement
      with reference to inductively coupled plasma optical emission spectroscopy
      (ICPOES) method was achieved when the developed sensor was applied for
      determination of Co(II) in aqueous samples.

PMID- 17531527
TI  - A fluorescent fluoride ion probe based on a self-organized ensemble of 5
      hydroxyflavone-Al(III) complex.
AB  - In the presence of Al(III) ions, 5-hydroxyflavone (5HF) through a complexation
      reaction in MeOH, shows dual fluorescence, characterized by a newly developed
      peak at 554nm upon excitation at 363nm. In this communication, the subsequent
      ligand exchange reaction of the complex with fluoride ion causing a fluorescence
      enhancement followed by a decrease in fluorescence intensity involving an
      intermediate mechanistic pathway, delivering a quantitative estimation route for
      fluoride ion in the concentration range from 5x10(-5) to 7x10(-4)M, has been
      reported. The ligand exchange reaction, without interference from other common
      anions, has been investigated by UV-vis and fluorescence spectroscopies combined
      with the AM1 semi-empirical self-consistent field quantum chemical calculations
      within UHF formalism in their ground state.

PMID- 17531528
TI  - Ultra-trace determination of S-nitrosothiols in blood samples by
      spectrofluorimetry with 8-(3',4'-diaminophenyl)-difluoroboradiaza-s-indacene.
AB  - Increasing evidence suggests that S-nitrosothiols (RSNO) may represent naturally
      occurring nitric oxide (NO) surrogates and function as intermediates in NO
      metabolism. In this work, a simple, sensitive, and selective micromethod is
      developed and validated for quantification of RSNO. A fluorescent probe 8-(3',4'
      diaminophenyl)-difluoroboradiaza-s-indacence (DABODIPY) is firstly used to label
      RSNO. The derivatization reaction is performed in aqueous medium at 30 degrees C
      for 15min in the presence of 6x10(-5)molL(-1)Hg2+ and the derivative is detected
      by fluorescence at lambda(ex)/lambda(em)=500/510nm. A linear function of
      concentration in the range of (2.0-600.0)x10(-8)molL(-1) is observed with a
      correlation coefficient of 0.9992 and detection limit of 1.2x10(-9)molL(-1)
      (S/N=3). This technique has been successfully applied to quantify RSNO in some
      human blood samples including healthy persons and patients suffering from
      cardiovascular diseases.

PMID- 17531529
TI  - ApoA-I induces a preferential efflux of monounsaturated phosphatidylcholine and
      medium chain sphingomyelin species from a cellular pool distinct from HDL(3)
      mediated phospholipid efflux.
AB  - Electrospray ionization tandem mass spectrometry (ESI-MS/MS) was used for a
      detailed analysis of cellular phospholipid and cholesterol efflux in free
      cholesterol (FC) loaded human primary fibroblasts and human monocyte-derived
      macrophages (HMDM) loaded with enzymatically modified LDL (E-LDL). Although both
      cell models differed significantly in their cellular lipid composition, a higher
      apoA-I specific efflux was found for monounsaturated phosphatidylcholine (PC)
      species together with a decreased contribution of polyunsaturated PC species in
      both cell types. Moreover, medium chain sphingomyelin (SPM) species SPM 14:0 and
      SPM 16:1 were translocated preferentially to apoA-I in both cell types. In
      contrast to fibroblasts, HMDM displayed a considerable proportion of cholesteryl
      esters (CE) in basal and apoA-I specific efflux media, most likely due to
      secretion of CE associated to apoE. Analysis of HDL(3) mediated lipid efflux from
      HMDM using D(9)-choline and (13)C(3)-FC stable isotope labeling revealed
      significantly different D(9)-PC and D(9)-SPM species pattern for apoA-I and
      HDL(3) specific efflux media, which indicates a contribution of distinct cellular
      phospholipid pools to apoA-I and HDL(3) mediated efflux. Together with a partial
      loading of fibroblasts and HMDM with HDL(3)-derived CE species, these data add
      further evidence for retroendocytosis of HDL. In summary, analysis of apoA
      I/ABCA1 and HDL(3) mediated lipid efflux by ESI-MS/MS demonstrated a preferential
      efflux of monounsaturated PC and medium chain SPM to apoA-I. Moreover, this is
      the first study, which provides evidence for distinct cellular phospholipid pools
      used for lipid transfer to apoA-I and HDL(3) from the analysis of phospholipid
      species pattern in HMDM.

PMID- 17531530
TI  - Lysophosphatidic acid induces prostate cancer PC3 cell migration via activation
      of LPA(1), p42 and p38alpha.
AB  - Prostate cancer cell migration is an essential event both in the progression of
      prostate cancer and in the steps leading to metastasis. We report here that
      lysophosphatidic acid (LPA), a potent bioactive phospholipid, induces prostate
      cancer PC3 cell migration via the activation of the LPA(1) receptor, which is
      linked to a PTX-sensitive activation mechanism of the mitogen-activated protein
      kinases (MAPK). Our results demonstrate that parallel activation of ERK1/2 and
      p38, but not JNK, is responsible for LPA-stimulated PC3 cell migration.
      Furthermore, using small interfering RNA (siRNA) technology, and overexpressing
      dominant-negative mutants of p38 MAPK isotypes of alpha, beta, gamma and delta,
      we have identified that the activation of ERK2 (p42) and p38alpha, but not of
      ERK1 and the other isoforms of p38 MAPK, is required for LPA-induced migration.
      Our study provides the first evidence for a functional role of p42 and p38alpha
      in LPA-induced mammalian cell migration, and also demonstrates, for the first
      time, that the receptor LPA(1) mediates prostate cancer cell migration. The
      results of the present study suggest that LPA, the receptor LPA(1), ERK2 and
      p38alpha are important regulators for prostate cancer cell invasion and thus
      could play a significant role in the development of metastasis.

PMID- 17531531
TI  - Low frequency repetitive transcranial magnetic stimulation over premotor cortex
      can improve cortical tremor.
AB  - OBJECTIVE: To examine the effects of a 30 min, 1 Hz subthreshold rTMS in a case
      of cortical tremor which is caused by hyperexcitability of sensorimotor cortex.
      METHODS: Stimulation was applied over primary and, in a second time, over
      premotor cortex (M1 and PMC, respectively). Tremor was monitored by
      accelerometers placed on the index fingers of hands outstretched, before and
      several times after rTMS. Each rTMS session consisted of 1800 pulses delivered at
      1 Hz with an intensity of 90% of resting motor threshold. RESULTS: PMC but not M1
      stimulation led to a decrease of the postural tremor (90% decrease of
      acceleration total spectral power). This functional benefit was associated to
      normalization of electrophysiologic parameters (short-interval intracortical
      inhibition and cortical silent period duration). Moreover, when stimulating PMC
      during two daily sessions, improvement of the tremor was longer than one day
      stimulation and this benefit was associated with functional improvement.
      CONCLUSIONS: This study shows that 1 Hz rTMS over premotor cortex can improve
      cortical tremor. SIGNIFICANCE: These results raise the interest of the motor
      cortical stimulation as a possible therapeutic target for treatment of action
      tremor.

PMID- 17531532
TI  - Relationship of periodic leg movements and severity of restless legs syndrome: a
      study in unmedicated and medicated patients.
AB  - OBJECTIVE: To evaluate the relationship of the severity of restless legs syndrome
      (RLS) as assessed by a subjective, patient-rated scale (International RLS Study
      Group Rating Scale, IRLS), and of periodic leg movements in sleep (PLMS) as an
      objective parameter, in two different patient populations. METHODS: Data of 200
      unmedicated patients with idiopathic RLS were evaluated. Group 1 (n=100)
      consisted of selected patients participating in the Pergolide European Australian
      RLS (PEARLS) study. Group 2 (n=100) represented an outpatient RLS population
      investigated in a Sleep Disorders Center. Additionally, Group 1 was also
      evaluated after a 6 week double-blind treatment period, where 47 patients
      received pergolide and 53 patients placebo. RESULTS: In unmedicated patients,
      IRLS scores correlated with the PLMS-arousal index (r=0.22, p=0.033) but not with
      the PLMS index in Group 1 while no correlation was found in Group 2. The change
      of the IRLS score under treatment in Group 1 correlated significantly both with
      the change of the PLMS index (r=0.42, p<0.001) and the change of the PLMS-arousal
      index (r=0.38, p<0.001). CONCLUSIONS: The IRLS adequately reflects treatment
      changes of PLMS indices. In unmedicated patients, the IRLS correlates with PLMS
      indices probably only in selected RLS populations with predefined PSG criteria
      and high PLM activity. SIGNIFICANCE: The IRLS is an appropriate subjective rating
      scale for measuring treatment effects in RLS.

PMID- 17531533
TI  - AutoCPAP initiation at home: optimal trial duration and cost-effectiveness.
AB  - BACKGROUND: The duration of automatic computer-controlled continuous positive
      airway pressure device (autoCPAP) initiation at home varies largely between sleep
      centers. Our objectives were to evaluate the cost-effectiveness and to find the
      optimal trial duration. METHODS: Of the 206 consecutive CPAP-naive patients with
      obstructive sleep apnea syndrome, who were referred to our hospital, 166 received
      autoCPAP for a 5-day trial at home. RESULTS: Of the 166 patients, 89 (15 women)
      showed a successful 5-day autoCPAP trial (normalized oximetry and mask-on time
      exceeding 4 h/day for at least 4 days). For the first trial day, 88 (53%)
      patients had normalized oximetry and a mask-on time exceeding 4 h. A 1-day
      autoCPAP trial EUR 668 was less cost-effective than a 5-day trial EUR 653, with
      no differences in values of efficient CPAP pressure or residual apnea-hypopnea
      index (AHI). The systematic requirement of oximetry monitoring raised the cost
      considerably from EUR 481 to EUR 668. CONCLUSIONS: In selected patients with
      obstructive sleep apnea, the optimal duration for initiating CPAP therapy at home
      by autoCPAP is 5 days. Although a 1-day trial was sufficient to determine the
      CPAP pressure requirement, it was not cost-effective and had a high rate of
      failure.

PMID- 17531534
TI  - CD24: a genetic checkpoint in T cell homeostasis and autoimmune diseases.
AB  - CD24 is widely used as a marker for differentiation of multiple lineages of cells
      and can provide costimulation for T cells, especially in non-lymphoid target
      organs. Recent studies demonstrate that CD24 controls an important genetic
      checkpoint for homeostasis and autoimmune diseases in both mice and humans.
      Understanding the molecular and cellular basis of CD24 function could provide
      important insights into T cell biology and autoimmunity.

PMID- 17531535
TI  - Molecular basis for prostaglandin production in hosts and parasites.
AB  - Prostaglandins (PGs) comprise a family of structurally related bioactive lipid
      mediators that are involved in various symptoms associated with parasitic
      diseases. The molecular mechanisms of PG biosynthesis in animals have been
      studied extensively. Currently, several lines of evidence link their production
      with parasites. In this review we discuss the roles of PGs in parasite
      pathogenesis and physiology and the recent advances in our understanding of the
      enzymology of PG production in various parasites.

PMID- 17531536
TI  - Consequences of the natural propensity of Leishmania and HIV-1 to target
      dendritic cells.
AB  - Recent studies have shown that both Leishmania and HIV type-1 (HIV-1) hijack
      dendritic cell (DC) functions to escape immune surveillance using an array of
      elaborate strategies. Leishmania has developed a variety of adaptations to
      disrupt cellular defense mechanisms, whereas HIV-1 targets DCs to achieve a more
      efficient dissemination. The capacity of Leishmania and HIV-1 to target DCs
      through a common cell-surface molecule, namely DC-SIGN (dendritic cell specific
      ICAM-3-grabbing non-integrin), points to a possible dangerous liaison between
      these two pathogens. This review explores our knowledge of how Leishmania and HIV
      1 interact dynamically with DCs, and how they exploit this cell type for their
      reciprocal benefit.

PMID- 17531537
TI  - The CD40/CD40 ligand system is involved in the pathogenesis of pemphigus.
AB  - The CD40/CD40 ligand (CD40L) system has never been investigated in autoimmune
      bullous diseases belonging to the pemphigus group in humans. Skin biopsy
      specimens from 21 patients with pemphigus vulgaris, 10 with pemphigus foliaceous
      and healthy volunteers were studied by immunohistochemistry (for CD40 and CD40L)
      and reversal transcriptase polymerase-chain reaction (for CD40L), while sera were
      analyzed by enzyme-linked immunosorbent assay for soluble CD40L. In all pemphigus
      specimens, the basal and suprabasal layers of the epidermis and perivascular
      infiltrating cells were CD40+. CD40L+ cells moderately infiltrated the
      perivascular and interstitial dermis of pemphigus specimens. CD40L mRNA was
      strongly evident in all pemphigus samples while no signal was detected in the
      healthy controls. The expression of soluble CD40L was significantly greater in
      pemphigus sera than in controls. We showed here that the CD40/CD40L system is
      upregulated both in lesional skin and in serum of patients with pemphigus.

PMID- 17531538
TI  - Outcome following preterm birth.
AB  - Preterm birth currently occurs in approximately 12% of pregnancies and appears to
      be increasing despite improvements in obstetric care. Improvements in neonatal
      care have led to increased survival, particularly at extreme prematurity, but
      survival may be associated with significant morbidity. This may be acute,
      reflecting the difficulties in supporting an individual in a hostile extrauterine
      environment to which they should not be exposed, or chronic, reflecting
      disturbances to fragile, immature body systems. Brain, lungs, intestines and eyes
      are particularly vulnerable and damage may be severe. For some infants the
      consequences of this damage may be permanent disability and impairment. Despite
      this, the limited information currently available suggests that adult outcomes
      may be comparable with those for infants born at term.

PMID- 17531539
TI  - The Hydro ThermAblator.
AB  - The Hydro ThermAblator system is a unique approach to endometrial ablation,
      employing constant direct visual control via hysteroscopy combined with a 'no
      touch' gravity flow of heated saline that treats the entire endometrial surface
      regardless of its topography. The automated controller helps to ensure
      reproducible results without the necessity for high operator skill. The system
      employs a safety feature that monitors the fluid level constantly within a closed
      system, so that loss of fluid through unsuspected uterine perforation occurring
      during dilatation can be diagnosed even though it may not be visually apparent to
      the operator. Results as judged by patient satisfaction, amenorrhoea rates and/or
      return to normal menstrual flow are excellent.

PMID- 17531540
TI  - Does attitude toward epilepsy mediate the relationship between perceived stigma
      and mental health outcomes in children with epilepsy?
AB  - OBJECTIVE: The purpose of this study was to examine the extent to which
      children's attitude toward epilepsy mediates the relationship between perceived
      stigma and the mental health outcomes of self-concept, behavioral problems, and
      social competence. METHOD: Subjects were 173 youth aged 9-14 who had been
      diagnosed and treated for epilepsy for at least 6 months. A secondary data
      analysis from a larger study was completed to test if the children's attitude
      mediated the relationship between stigma and mental health outcomes using
      multiple regression. RESULTS: Children's attitude was found to mediate the
      relationships between stigma and self-concept and behavior problems,
      respectively. In contrast, attitude did not mediate the relationship between
      stigma and social competence. CONCLUSIONS: Results suggest that enhancing a more
      positive attitude toward having epilepsy might help improve problems with poor
      self-concept or behavior problems, but might not influence social competence.

PMID- 17531541
TI  - Autism: the first firm finding = underconnectivity?
AB  - In January 2005, J.R. Hughes and M. Melyn published an electroencephalographic
      study on autistic children and found 46% with seizures and also a relatively high
      prevalence of 20% with epileptiform discharges but without any clinical seizures
      (Clin EEG Neurosci 2005;36:15-20). Because the discharges have always been viewed
      as focal events and the clinical seizures as requiring spread, the conclusion
      from these data was that children with autism may have a deficiency of
      corticocortical fibers. Since that time many MRI and functional MRI studies have
      been published confirming that one of the first findings in this devastating
      condition is underconnectivity. Specific findings are the thinning of the corpus
      callosum and the reduced connectivity, especially with the frontal areas and also
      the fusiform face area. Other studies involving positron emission tomography
      scans, magnetoencephalography, and perception have added to the evidence of
      underconnectivity. One final point is the initial overgrowth of white matter in
      the first 2 years of life in autistic children, followed later by arrested
      growth, resulting in aberrant connectivity; myelination of white matter will
      likely be significant in the etiology of autism.

PMID- 17531542
TI  - Beneficial effects of antiepileptic medication on absence seizures and cognitive
      functioning in children.
AB  - In this prospective clinical study, the effects on cognitive functioning of
      absence seizures, epileptiform EEG discharges, and their abolishment by
      antiepileptic medication were evaluated in patients newly diagnosed with
      childhood absence epilepsy or juvenile absence epilepsy. Eleven children in the
      study group and ten age- and gender-matched controls with mild asthma underwent
      combined video/EEG and neurocognitive assessment (IQ, fine-motor fluency,
      attention, visual and spatial memory). The neuropsychological assessment was
      repeated after the introduction of antiepileptic medication. Ten children with
      absence epilepsy became clinically seizure free. The study group improved in
      attention, fine-motor fluency, and visual memory. The controls improved only in
      fine-motor and attention skills. Duration of generalized 3-Hz spike-wave
      discharges and clinical absence seizures was negatively correlated with
      performance on the visual memory task. Cessation of seizures induced by
      antiepileptic medication may support neurocognitive functioning in children.

PMID- 17531543
TI  - Purification and characterization of an acetylcholinesterase from the infective
      juveniles of Heterorhabditis bacteriophora.
AB  - Acetylcholinesterases (AChEs) have been estimated in the infective juveniles
      (IJs) of eight different strains of heterorhabditid nematodes. The enzyme content
      ranged from 45.6 to 421.3 units/10(5) IJs with specific activity 34.0 to 82.6
      units/mg protein. The isoenzyme patterns revealed the existence of two-slow
      moving isoforms. Heterorhabditis bacteriophora AChE1A has been purified from the
      IJs of the heterorhabditid nematode strain of the highest enzymatic activity to
      homogeneity by ammonium sulfate precipitation, gel filtration on Sephacryl S-200
      and DEAE-Sepharose. The specific activity of the purified enzyme was 1378.1
      units/mg protein with purification fold 17.5 over crude extract. The enzyme has a
      pH optimum at 7.5. The optimum temperature for enzyme activity and stability was
      35 degrees C. The activation energy was calculated to be 9.0 kcal/mol. The enzyme
      hydrolyzes acetylthiocholine (AcSCh), propionylthiocholine (PrSCh), S
      butyrylthiocholine (BuSCh) and benzoylthiocholine (BzSCh) iodides with relative
      rate 100, 74.6, 41.7 and 22.2%, respectively. It displayed an apparent Michaelis
      Menten behavior in the concentration range from 0.1 to 2 mM for the three former
      substrates with Km values 0.27, 0.42 and 0.59 mM, respectively. H. bacteriophora
      ChE1A is an AChE since it hydrolyzed AcSChI at higher rate than the other
      substrates and displayed excess substrate inhibition with AcSChI at
      concentrations over 2 mM. It was inhibited by eserine and BW284C51, but not by
      iso-OMPA. Its biochemical properties were compared with those reported for
      different species of insects as target hosts for heterorhabditid nematodes and
      animal parasitic nematodes.

PMID- 17531544
TI  - FreeViz--an intelligent multivariate visualization approach to explorative
      analysis of biomedical data.
AB  - Visualization can largely improve biomedical data analysis. It plays a crucial
      role in explorative data analysis and may support various data mining tasks. The
      paper presents FreeViz, an optimization method that finds linear projection and
      associated scatterplot that best separates instances of different class. In a
      single graph, the resulting FreeViz visualization can provide a global view of
      the classification problem being studied, reveal interesting relations between
      classes and features, uncover feature interactions, and provide information about
      intra-class similarities. The paper gives mathematical foundations of FreeViz,
      and presents its utility on various biomedical data sets.

PMID- 17531545
TI  - Detection of colorectal disease by stool defensin assay: an exploratory study.
AB  - BACKGROUND & AIMS: Alpha-defensins 1-3 (human neutrophil peptides [HNP]1-3),
      reported to be elevated in tumor tissue and serum of patients with colorectal
      cancer (CRC), have not been studied in stool. We evaluated the neoplasm
      specificity of HPN1-3 and their discriminant value as stool markers for CRC.
      METHODS: Protein and mRNA expression of HPN1-3 were assayed in CRC cell lines,
      microdissected CRC and normal epithelium, and white blood cells. HNP1-3 proteins
      in stools were quantified in blinded fashion from 30 normal subjects, 20 patients
      with CRC, 10 with a large colorectal adenoma, 10 with upper gastrointestinal
      cancer, and 10 with IBD. Stool lactoferrin was also quantified. RESULTS: HPN1-3
      proteins were not detected in CRC cell lines but were high (>4000 ng/mL) in white
      blood cells. mRNA levels of HPN1-3 were comparably low in CRC cell lines,
      microdissected CRC, and normal colon epithelium, but they were >1000-fold and
      >30,000-fold higher in white blood cells and neutrophils, respectively. Mean
      stool HPN1-3 levels were 17 ng/mL with normals, 125 ng/mL with CRC, 62 ng/mL with
      adenoma, 63 ng/mL with upper gastrointestinal cancer, and 231 ng/mL with IBD (P <
      .01 for each patient group vs normals). HPN1-3 levels in IBD were higher than in
      CRC (P = .04). At 90% specificity, sensitivity of stool defensins was 35% for
      CRC, 40% for adenoma, 40% for upper gastrointestinal cancers, and 80% for IBD.
      Stool defensins and lactoferrin levels correlated (R2 = 0.70, P < .001).
      CONCLUSIONS: Alpha-defensins 1-3 levels are nonspecifically elevated in stools
      from patients with colorectal neoplasia and likely originate from white blood
      cells. Alpha-defensins 1-3 in stool might serve as markers of inflammatory bowel
      conditions.

PMID- 17531546
TI  - The ATR pathway: fine-tuning the fork.
AB  - The proper detection and repair of DNA damage is essential to the maintenance of
      genomic stability. The genome is particularly vulnerable during DNA replication,
      when endogenous and exogenous events can hinder replication fork progression.
      Stalled replication forks can fold into deleterious conformations and are also
      unstable structures that are prone to collapse or break. These events can lead to
      inappropriate processing of the DNA, ultimately resulting in genomic instability,
      chromosomal alterations and cancer. To cope with stalled replication forks, the
      cell relies on the replication checkpoint to block cell cycle progression,
      downregulate origin firing, stabilize the fork itself, and restart replication.
      The ATR (ATM and Rad3-related) kinase and its downstream effector kinase, Chk1,
      are central regulators of the replication checkpoint. Loss of these checkpoint
      proteins causes replication fork collapse and chromosomal rearrangements which
      may ultimately predispose affected individuals to cancer. This review summarizes
      our current understanding of how the ATR pathway recognizes and stabilizes
      stalled replication forks.

PMID- 17531547
TI  - Detection of two Alu insertions in the CFTR gene.
AB  - BACKGROUND: LINE-1 (long interspersed element-1) or L1-mediated
      retrotransposition is a potent force in human genome evolution and an occasional
      cause of human genetic disease. Since the first report of two de novo L1
      insertions in the F8 gene causing hemophilia A, more than 50 L1-mediated
      retrotranspositional events have been identified as causing human genetic
      disease. However, a significant bias has generally militated against the
      detection of these pathological events at autosomal loci. Based upon this and
      other observations, we surmised that some previously unresolved cystic fibrosis
      chromosomes might carry hitherto undetected L1-mediated retrotranspositional
      insertions at the CFTR locus. This study represents an attempt to identify such
      mutational events. METHODS: 100 previously unresolved cystic fibrosis chromosomes
      were carefully reanalyzed using quantitative high-performance liquid
      chromatography (QHPLC). RESULTS: Two simple Alu insertions were identified in the
      CFTR gene, within exons 16 and 17b respectively. CONCLUSIONS: Our findings have
      not only revealed a previously unknown mutational mechanism responsible for
      cystic fibrosis but also represent an important addition to the already diverse
      spectrum of known CFTR gene mutations. Experience with the CFTR gene suggests
      that pathological L1-mediated retrotranspositional events may also have been
      overlooked at other gene loci and should always be considered in cases that
      appear to be refractory to analysis.

PMID- 17531548
TI  - Blunted ventilatory response to hypoxia/hypercapnia in mice with cigarette smoke
      induced emphysema.
AB  - It has been reported that the degree of emphysema induced by chronic cigarette
      smoke (CS) is greater in female C3H/HeN mice as compared to other mouse strains.
      We hypothesized that these mice would develop the similar major characteristics
      seen in hypercapnic patients with chronic obstructive pulmonary disease (COPD),
      including emphysema, pulmonary inflammation, hypercapnia/hypoxemia, rapid
      breathing, and attenuated ventilatory response (AVR). Mice were exposed either to
      CS or filtered air (FA) for 16 weeks. After exposure, arterial blood gases and
      minute ventilation were measured before and during chemical challenges in
      anesthetized and spontaneously breathing mice. We found that as compared to FA,
      CS exposure caused emphysema and pulmonary inflammation associated with: (1)
      hypercapnia and hypoxemia, (2) rapid breathing, and (3) AVR to 25 breaths of pure
      N(2), 5% CO(2) alone, and 5% CO(2) coupled with 10% O(2). The similarity of these
      pathophysiological characteristics between our mouse model and COPD patients
      suggests that this model could be effectively applied to study COPD
      pathophysiology, especially central mechanisms of the AVR genesis.

PMID- 17531549
TI  - Determination of ornithine in human plasma by hydrophilic interaction
      chromatography-tandem mass spectrometry.
AB  - The amino acid ornithine (Orn) acts as a vital part in the physiologically
      fundamental urea cycle. As such, it is a main intermediate in the catabolic
      breakdown as well as in the synthesis of arginine and is involved in many other
      metabolic pathways with potential clinical implications. We here describe a LC-MS
      MS method for the detection of Orn in human plasma which is fast, easy and
      precise. The sample preparation comprises only protein precipitation and the
      addition of the isotopic labeled I.S. The analytes are separated by hydrophilic
      interaction chromatography (HILIC) in less than 4min on a silica column with an
      isocratic mobile phase consisting of 0.1% trifluoroacetic acid in water and
      acetonitrile in the ratio of 25:75. Orn and its I.S. are detected and quantified
      by APCI tandem mass spectrometry. The calibration function is linear from 7.5 to
      205 micromol/l and covers the range of concentrations found in patients
      undergoing different clinical interventions. The quantification results are
      independent with regard to the biological matrix analyzed. The intra-day and
      inter-day relative standard deviations are 1.1% and 3.5%, respectively. As an
      application of the described method in clinical investigations, we report
      arginine and ornithine plasma concentration results from an arginine
      supplementation study enrolling healthy volunteers and patients suffering from
      hypercholesterolemia. After oral dosing of 110 mg/kg arginine, ornithine plasma
      concentrations rose from 54 to 148 micromol/l after 2h and were back to baseline
      after 24h. However, arginine to ornithine ratios kept constant during the
      complete observation time.

PMID- 17531550
TI  - Capillary electrophoretic immunoassay for alpha-fetoprotein with
      chemiluminescence detection.
AB  - A capillary electrophoretic immunoassay with chemiluminescence detection (CEIA
      CL) using a non-competitive format for analyzing tumor marker alpha-fetoprotein
      (AFP) has been developed. In this method, antigen (Ag) AFP reacts with an excess
      amount of horseradish peroxidase (HRP)-labeled antibody (Ab*). The free Ab* and
      the bound Ab*-Ag complex produced in the solution are separated by CE in a
      separation capillary. Then they catalyze the reaction of enzyme substrate luminol
      and H(2)O(2) in a reaction capillary following the separation capillary.
      Parameters affecting the CE separation and CL detection were investigated. Under
      the optimal conditions, the free Ab* and the Ab*-Ag complex were well separated
      within 4 min, the linear range and the detection limit (S/N=3) for AFP were 5-500
      ng/ml and 0.85 ng/ml (1.2 x 10(-11)M), respectively. The proposed method has been
      applied satisfactorily in the analysis of human sera samples.

PMID- 17531551
TI  - Toward an anthropometric history of provincial France, 1780-1920.
AB  - A sample of 237,782 individual observations was obtained in four areas of France:
      rural Alsace, urban Alsace, Limousin, and Brie (Ile-de-France). Trends in the
      biological standard of living of conscripts born in these regions between 1780
      and 1920 fit well with the recently estimated trends for other parts of Europe.
      While heights were relatively low, they did not decline much preceding the
      Revolution in 1789. During the first half of the 19th Century heights varied
      considerably both spatially and longitudinally, indicating the contrasting
      effects of modernization among the four areas. Conscripts from the least
      productive agricultural area, Limousin, were the shortest. Heights in Alsace
      remained essentially unchanged during the first half of the 19th Century, but
      those in Brie increased after 1820 and those in Limousin after 1840. The positive
      trend became more general after 1870, though Brie alone showed the considerable
      negative impact of the agricultural depression of the last quarter of the 19th
      Century. Heights diverged until 1850 and converged thereafter. In Limousin, the
      annual height of conscripts is positively correlated with the weight of cattle.
      By the early decades of the 20th Century, a marked, long-term increase in
      anthropometric growth had occurred in these four regions, as elsewhere in Europe.
      The regional estimates correspond well to the national trends estimated by Komlos
      and Weir except that they show the great local variation in height until the turn
      of the 20th Century.

PMID- 17531552
TI  - Colonoscopy: Not quite the gold standard.

PMID- 17531553
TI  - Treating ETTCL: A matter of early diagnosis and chemotherapy strategies.

PMID- 17531554
TI  - The anionic peptide fraction is present on the gallbladder apical epithelium and
      favours biliary cholesterol absorption.
AB  - BACKGROUND/AIMS: We investigated (a) in vitro and in vivo the changes of biliary
      mass of the anionic peptide fraction, apolipoproteinA-I, immunoglobulin-A,
      albumin and cholesterol over time in the excluded gallbladder and (b) in vivo the
      localization in the gallbladder epithelium of the anionic peptide fraction and
      cholesterol absorbed from bile. METHODS: Native bile was substituted with pig
      bile containing radiolabeled cholesterol in the in vitro isolated intra
      arterially perfused pig gallbladder (n=9) and in vivo in anestethized pigs with
      excluded gallbladders (n=6). The amount of cholesterol (scintillation counting)
      and proteins (enzyme-linked immunosorbent assay) in gallbladder bile were
      measured over time. The localization of the anionic peptide fraction and
      cholesterol absorbed from bile in the gallbladder epithelium was studied in vivo
      by immunohistochemistry and fluoro-phospho-imager analysis. RESULTS: The rate of
      biliary cholesterol disappeared from bile was a function of the initial
      concentration and of the biliary mass changes over time of the anionic peptide
      fraction, but not of that of the other biliary proteins. The anionic peptide
      fraction colocalized with biliary cholesterol absorbed by the gallbladder on the
      apical side of gallbladder epithelial cells. CONCLUSIONS: These data indirectly
      suggest that biliary anionic peptide fraction could favour biliary cholesterol
      absorption by the gallbladder epithelium.

PMID- 17531555
TI  - Treatment cost of ulcerative colitis is apheresis with Adacolumn cost-effective?
AB  - BACKGROUND: Scarce data are available in Europe on the cost of treatment for
      ulcerative colitis (UC). AIM: To assess the cost of illness of moderate-to-severe
      UC in two scenarios: traditional treatment versus alternative treatment
      incorporating granulocyte, monocyte adsorption - apheresis (GMA-Apheresis;
      Adacolumn). To determine the relative cost-effectiveness of both options in
      steroid-dependent patients. METHODS: One-year cost-of-illness and cost
      effectiveness analysis from the third-payer perspective using a decision tree
      model was carried out. Probabilities of each event were derived from the
      literature and an expert panel. Direct medical costs were obtained from official
      sources (euro2004). Effectiveness was measured by the proportion of patients
      achieving clinical remission. RESULTS: The average annual cost per patient
      treated with traditional treatment was estimated to be euro6740; with GMA
      Apheresis, the cost was estimated to be euro6959. In steroid-dependent patients,
      the average annual cost was euro6059 and euro11,436, respectively. The proportion
      of patients achieving clinical remission with GMA-Apheresis was 22.5% higher. As
      second- and third-line therapy, a new course of corticosteroids and surgery was
      avoided in 18.5 and 4% of patients, respectively. CONCLUSIONS: Incorporating GMA
      Apheresis (Adacolumn) in the therapeutic management of moderate-to-severe UC
      patients is cost-effective and implies savings related to the reduction of
      adverse effects derived from corticosteroid use and to the decreased number of
      surgical interventions.

PMID- 17531556
TI  - Clinical significance of anti-Saccharomyces cerevisiae antibody (ASCA) in Korean
      patients with Crohn's disease and its relationship to the disease clinical
      course.
AB  - BACKGROUNDS/AIMS: The implications of anti-Saccharomyces cerevisiae antibody for
      the diagnosis and the clinical course of Crohn's disease have been reported in
      Western countries, but rarely in Korea with its very different environmental and
      genetic backgrounds. We aimed to evaluate whether anti-S. cerevisiae antibody
      expression is associated with diagnostic findings, stratified Vienna
      classification phenotypes, disease activity and clinical course in Korean
      patients with Crohn's disease. MATERIALS/METHODS: One hundred and fifteen
      patients with Crohn's disease, diagnosed and treated between 1990 and 2004 at
      Severance Hospital, Yonsei University and followed for at least 2 years, were
      included in this study. Anti-S. cerevisiae antibody was detected by an indirect
      immunofluorescence assay using EUROIMMUN kits. Information collected during
      treatment included demography, Vienna classification phenotype, clinical
      manifestation, laboratory tests, treatment modality and surgery rate. Disease
      activity was measured monthly using the Harvey-Bradshaw index. RESULTS: The anti
      S. cerevisiae antibody prevalence was 38.3% in Crohn's disease patients. There
      was no difference in anti-S. cerevisiae antibody expression between genders. The
      mean age at diagnosis was younger for the anti-S. cerevisiae antibody positive
      group than the negative group (25.3 years versus 29.7 years, p<0.05). Clinical
      manifestations and laboratory tests at diagnosis did not differ between the
      groups. The anti-S. cerevisiae antibody positive group had increased
      fibrostenosis (B2) and penetration (B3) compared to negative group, as determined
      by the Vienna classification (75.0% versus 53.5%, p<0.05). Anti-S. cerevisiae
      antibody positive patients were admitted to the hospital more frequently than
      anti-S. cerevisiae antibody negative patients (p<0.05). The yearly cumulative
      Harvey-Bradshaw index score was higher in the anti-S. cerevisiae antibody
      positive group than in the negative group during the follow-up period (p<0.05).
      In addition, steroid (72.7% versus 52.1%, p<0.05) and immunosuppressive (45.5%
      versus 23.9%, p<0.05) treatments were more frequently given to the anti-S.
      cerevisiae antibody positive group. CONCLUSIONS: Our data demonstrate that anti
      S. cerevisiae antibody positive Crohn's disease patients had a more severe
      clinical course and thus often required more aggressive medical treatment.

PMID- 17531557
TI  - Benign pancreatic hyperenzymemia.
AB  - Benign pancreatic hyperenzymemia is a newly identified syndrome characterized by
      an abnormal increase in serum pancreatic enzymes in the absence of pancreatic
      disease. The hyperenzymemia can occur sporadically or in a familial form, and all
      of the pancreatic enzymes show elevations. Although the condition is persistent,
      the enzyme elevations fluctuate considerably, even temporarily returning to
      normal levels at times. In this review the main characteristics of this syndrome
      are described.

PMID- 17531558
TI  - Genomic stability prevails in North-African hepatocellular carcinomas.
AB  - The molecular pathogenesis of hepatocellular carcinoma, a tumour characterized by
      a vast clinical heterogeneity, remains unexplored outside Europe and Eastern
      Asia. We analysed by direct sequencing or loss of heterozygosity assay, the
      common targets of genomic alterations in 42 hepatocellular carcinomas collected
      in western North-Africa. Overall, genomic instability was uncommon, allelic
      losses affecting mostly chromosomes 1p, 4q, 8p and 17p (24-28% of cases). CTNNB1
      and TP53 were infrequently mutated (9 and 17% of cases, respectively).
      Surprisingly, TP53 mutation R249S, diagnostic of aflatoxin B1 exposure, usually
      frequent in Africa, was exceptional (one case), indicating that in western North
      Africa, hepatocellular carcinoma genetics differs markedly from that of the
      remainder of the continent.

PMID- 17531559
TI  - Bile salts regulate proliferation and apoptosis of liver cells by modulating the
      IGF1 system.
AB  - BACKGROUND: In different cell types, the insulin-like growth factor 1 and its
      receptor modulate growth, apoptosis and damage repair in cooperation with
      estrogen receptors. AIM: To evaluate the involvement of the insulin-like growth
      factor 1 system and estrogen receptors in bile salts modulation of
      apoptosis/proliferation of hepatocytes and cholangiocytes. Primary cultures of
      rat hepatocytes and cholangiocytes were exposed to glycochenodeoxycholate or
      tauro-CDC in the presence or absence of insulin-like growth factor 1 receptor
      blocking antibody (alphaIR3), small interfering RNA for insulin-like growth
      factor 1, 17beta-estradiol or estrogen receptor antagonist (ICI 182,780).
      Proliferation was evaluated by proliferating cell nuclear antigen Western blot
      and apoptosis by measuring caspase-3 activity or annexin-V. RESULTS: In
      hepatocytes, the insulin-like growth factor 1 receptor blocker enhanced
      glycochenodeoxycholate-induced apoptosis and caused tauro-CDC to promote
      apoptosis. 17Beta-estradiol or the estrogen receptor antagonist (ICI 182,780) did
      not influence the apoptotic effect of glycochenodeoxycholate. In cholangiocytes,
      both glycochenodeoxycholate and tauro-CDC induced proliferation at 100microM,
      while they induced apoptosis at 1mM with a more pronounced effect of
      glycochenodeoxycholate. Apoptosis induced by 1mM glycochenodeoxycholate or tauro
      CDC in cholangiocytes was enhanced by blocking insulin-like growth factor 1
      receptor or by silencing insulin-like growth factor 1. 17Beta-estradiol
      counteracts glycochenodeoxycholate-induced cholangiocyte apoptosis by enhancing
      insulin-like growth factor 1 secretion and activating the insulin-like growth
      factor 1 system. CONCLUSIONS: Modulation of the IGF1 system could represent a
      potential strategy for the management of bile salts-induced liver injury.

PMID- 17531560
TI  - Expression of HSP70 and JNK-related proteins in human liver cancer: Potential
      effects on clinical outcome.
AB  - BACKGROUND: Activation of stress-activated protein kinase/c-Jun N-terminal kinase
      was inhibited in cells, in which heat shock protein70 was induced to a high
      level, indicating that heat shock protein70 might be anti-apoptosis protein. AIM:
      We examined the expression of heat shock protein70 and c-Jun N-terminal kinase
      signal transduction pathway in human liver carcinoma to explore their
      relationship and clinical parameters. PATIENTS AND METHODS: The expression of
      heat shock protein70, c-Jun N-terminal kinase1, c-Jun N-terminal kinase2 and c
      Jun were detected immunohistochemically in 62 samples of liver cancer. Western
      blot was used to confirm immunostaining results. RESULTS: Heat shock protein70
      expression showed a positive correlation with the malignant differentiation in
      liver carcinoma (r=0.449, P<0.0005). The expression of c-Jun N-terminal kinase1,
      c-Jun N-terminal kinase2, and c-Jun showed a negative correlation with the
      malignant differentiation in liver carcinoma (r=-0.351, P=0.005; r=-0.303,
      P=0.017; r=-0.302, P=0.017). Heat shock protein70 expression was correlated with
      c-Jun N-terminal kinase1 (r=-0.385, P=0.002), c-Jun N-terminal kinase2 (r=-0.309,
      P=0.015) and c-Jun (r=-0.302, P=0.017). Expression of heat shock protein70, as
      well as c-Jun N-terminal kinase1, was correlated with recurrence-free survival
      after the resection. Heat shock protein70 was associated with prognosis
      (P=0.004). CONCLUSION: Expression of heat shock protein70 and c-Jun N-terminal
      kinase-related proteins might be an indicator of malignant potential in liver
      carcinoma. The balance between heat shock protein70 and c-Jun N-terminal kinase
      related protein may increase the stability of liver cancer cells in stress.
      Negative expression of heat shock protein70 might be a protective factor of
      recurrence of liver carcinoma.

PMID- 17531561
TI  - Disappointing outcome of autologous stem cell transplantation for enteropathy
      associated T-cell lymphoma.
AB  - BACKGROUND: Despite treatment, enteropathy-associated T-cell lymphoma has a very
      poor outcome. Chemotherapy can be complicated by small bowel perforation,
      gastrointestinal bleeding and development of enterocolic fistulae. Here we report
      on the feasibility, safety and efficacy of high-dose chemotherapy followed by
      autologous stem cell transplantation in patients with enteropathy-associated T
      cell lymphoma (three upfront and one at relapse), with or without prior partial
      small bowel resection. METHODS: Four patients [two males, two females, mean age
      65 years (range 60-69 years)] received high-dose chemotherapy followed by
      autologous stem cell transplantation. Partial small bowel resection has been
      performed in three patients. RESULTS: All four patients completed the
      mobilization and leucopheresis procedures successfully and subsequently received
      conditioning chemotherapy and transplantation. Engraftment occurred in all
      patients. No major non-haematological toxicity or transplantation-related
      mortality was observed. One patient has ongoing complete remission 32 months
      after transplantation. Three patients died from relapse within few months after
      autologous stem cell transplantation. CONCLUSIONS: Autologous stem cell
      transplantation seems unsatisfactory for patients with enteropathy-associated T
      cell lymphoma. More intensive conditioning and aggressive chemotherapy with/or
      without targeted immunotherapy as well as allogenous stem cell transplantation
      needs to be explored.

PMID- 17531562
TI  - Vascular smooth muscle tumors: review of the literature.
AB  - Vascular smooth muscle tumors are very rare. They can be benign or malign.
      Intravascular leiomyomatosis is a benign neoplasm that extends through the veins
      and caries significant morbidity. Angioleiomyoma is a benign neoplasm of the
      extremities that caries minimal morbidity. Vascular leiomyosarcomas are malign
      neoplasms derived from vascular smooth cells. They are usually localized to the
      inferior vena cava, but can also arise from the pulmonary arteries or veins or
      other peripheral vessels. This study reviews literature for epidemiology,
      clinical presentation, diagnosis and management of patients with vascular smooth
      muscle tumors.

PMID- 17531563
TI  - Electrosurgical excision technique for the treatment of multiple cutaneous
      lesions in neurofibromatosis type I.
AB  - Neurofibromatosis I (NF1) is an autosomal dominant disease that presents with
      multiple cutaneous lesions often numbering into the 500-1000 range. In addition
      to the psychosocial implications, there are limited surgical options for this
      condition. A series of 97 consecutive patients with NF1 presented with numerous
      cutaneous lesions. Treatment involved electrocautery excision of the lesions
      using a handheld device in one or more stages. This technique resulted in the
      removal of large numbers of lesions in limited stages, with minimal scarring,
      minor discomfort and high patient acceptance. For patients with NF1, single or
      multistage excision of cutaneous lesions using electrocautery produces an
      acceptable aesthetic result with high patient satisfaction.

PMID- 17531564
TI  - Structural autosomal imbalance and oesophageal defects: addendum to the article
      by Felix et al. (2007).
AB  - Information about approximately 25 additional cases of oesophageal defects in
      patients with structural autosomal imbalance (in addition to 30 cases already
      mentioned in the article by Felix et al.) may facilitate search for the genes
      responsible for these defects.

PMID- 17531565
TI  - Transmitted cytogenetic abnormalities in patients with mental retardation:
      pathogenic or normal variants?
AB  - Knowing the origin of cytogenetic abnormalities detected in individuals with
      mental retardation and dysmorphic features is essential to genetic counselling of
      affected families. To illustrate this, we report on six families with transmitted
      cytogenetic abnormalities and discuss the genotype-phenotype correlations,
      including the possibility of the abnormalities being normal genomic variants. The
      abnormalities were detected using metaphase HR-CGH; their size was estimated to
      range from 1.6 to 7.5 Mb using tiling path array-CGH and real-time PCR. The
      abnormalities were transmitted through two to four generations and included
      interstitial deletions of 1p31.3-p32.1, 2q13, 10q11.21-q11.23, and 13q31.1; a
      duplication of 1p34.1-p34.2; and in one family both a deletion of 18q21.1 and a
      duplication of 4q35.1-q35.2. The probands were mentally retarded and had
      nonspecific dysmorphic features except for one patient with the Bohring-Opitz
      syndrome. We considered the abnormalities in two families to be clinically
      significant: In one family, the proband's brain abnormality was comparable to
      previously reported abnormalities in individuals with a similar duplication of
      1p31-p32. Congenital heart disease was previously mapped to the chromosomal
      region of 18q that was affected in the proband of another family. The carrier
      parents in both families had mild clinical features. In two families the
      abnormalities were considered as coincidental findings, and in two further
      families the abnormalities were insufficient to explain the phenotypes of the
      probands but possibly were related to a milder phenotype in other family members.
      These cases illustrate the need for careful assessment of the extended family in
      order to interpret the phenotypic consequences of abnormalities identified using
      array-CGH.

PMID- 17531566
TI  - Relation of body mass index to outcome in patients with known or suspected
      coronary artery disease.
AB  - Increased body mass index (BMI), a parameter of total body fat content, is
      associated with an increased mortality in the general population. However, recent
      studies have shown a paradoxic relation between BMI and mortality in specific
      patient populations. This study investigated the association of BMI with long
      term mortality in patients with known or suspected coronary artery disease. In a
      retrospective cohort study of 5,950 patients (mean age 61 +/- 13 years; 67% men),
      BMI, cardiovascular risk markers (age, gender, hypertension, diabetes, current
      smoking, angina pectoris, old myocardial infarction, heart failure,
      hypercholesterolemia, and previous coronary revascularization), and outcome were
      noted. The patient population was categorized as underweight, normal, overweight,
      and obese based on BMI according to the World Health Organization classification.
      Mean follow-up time was 6 +/- 2.6 years. Incidences of long-term mortality in
      underweight, normal, overweight, and obese were 39%, 35%, 24%, and 20%,
      respectively. In a multivariate analysis model, the hazard ratio (HR) for
      mortality in underweight patients was 2.4 (95% confidence interval [CI] 1.7 to
      3.7). Overweight and obese patients had a significantly lower mortality than
      patients with a normal BMI (HR 0.65, 95% CI 0.6 to 0.7, for overweight; HR 0.61,
      95% CI 0.5 to 0.7, for obese patients). In conclusion, BMI is inversely related
      to long-term mortality in patients with known or suspected coronary artery
      disease. A lower BMI was an independent predictor of long-term mortality, whereas
      an improved outcome was observed in overweight and obese patients.

PMID- 17531567
TI  - Prognostic implications of dipyridamole or dobutamine stress echocardiography for
      evaluation of patients > or =65 years of age with known or suspected coronary
      heart disease.
AB  - This study investigated the value of pharmacologic stress echocardiography for
      risk stratification of patients > or =65 years of age. The study cohort consisted
      of 2,160 patients > or =65 years of age (1,257 men, mean +/- SD 71 +/- 5 years of
      age) undergoing dipyridamole (n = 1,521) or dobutamine (n = 639) stress
      echocardiography for evaluation of known (n = 913) or suspected (n = 1,247)
      coronary artery disease. Of 2,160 patients, 753 (35%) had a normal test result,
      whereas 772 (36%) showed a myocardial ischemic pattern and 635 (29%) a scar
      pattern. During a median follow-up of 26 months, 241 deaths and 87 nonfatal
      myocardial infarctions occurred. Patients (n = 568) undergoing revascularization
      were censored. Of 16 analyzed variables, age (hazard ratio [HR] 1.07 per unit
      increment), wall motion score index at rest (HR 2.63 per unit increment),
      ischemia at stress echocardiography (HR 1.81), and diabetes (HR 1.57) were
      multivariable predictors of death, whereas age (HR 1.06 per unit increment),
      ischemia at stress echocardiography (HR 2.60), wall motion score index at rest
      (HR 1.98 per unit increment), scar pattern (HR 1.99), and diabetes (HR 1.48) were
      multivariable predictors of death or myocardial infarction. Using an interactive
      stepwise procedure, stress echocardiography showed incremental prognostic value
      over clinical and echocardiographic data at rest, which decreased with increasing
      age. In addition, the annual hard event rate associated with a normal test result
      progressively increased with age. In conclusion, pharmacologic stress
      echocardiography provides useful prognostic information in patients > or =65
      years of age. However, its prognostic value decreases with increasing age.

PMID- 17531568
TI  - Patterns of aspirin dosing in non-ST-elevation acute coronary syndromes in the
      CRUSADE Quality Improvement Initiative.
AB  - Recent studies have suggested that low-dose aspirin has preserved benefit with
      less bleeding compared with standard-dose aspirin when given with or without
      clopidogrel in patients with high-risk non-ST-segment elevation acute coronary
      syndromes (NSTE ACSs). We evaluated 22,618 patients with NSTE ACSs and high-risk
      features (ischemic ST-segment changes and/or positive cardiac markers) from 369
      hospitals included in the CRUSADE initiative from May 4, 2003 to September 30,
      2004. We analyzed acute (<24 hours of admission) and discharge aspirin doses in
      relation to concomitant clopidogrel use and other clinical predictors. Dosing of
      aspirin in the first 24 hours was as follows: 17.3% of patients (n = 3,911)
      received 81 mg, 13.5% (n = 3,062) received 162 mg, 67.4% (n = 15,247) received
      325 mg, and 1.8% (n = 398) received >325 mg. Use of lower dose aspirin increased
      at discharge: 40.2% (n = 7,524) received 81 mg, 3.1% (n = 579) received 162 mg,
      and 55.7% (n = 10,423) received 325 mg. In patients who received concomitant
      clopidogrel at discharge (n = 12,635), 37.6% received aspirin 81 mg and 58.5%
      received 325 mg. Compared with patients who did not receive concomitant discharge
      clopidogrel (n = 4,772), 44.0% received aspirin 81 mg and 51.2% received 325 mg.
      Use of aspirin 81 mg was significantly lower in patients undergoing percutaneous
      coronary intervention (31.5% vs 46.2%, p <0.0001). In conclusion, most patients
      with high-risk NSTE ACSs in the United States continue to be treated with aspirin
      325 mg at discharge with and without concomitant clopidogrel, despite recent
      studies that have shown a better safety profile with low-dose aspirin.

PMID- 17531569
TI  - Comparison of characteristics of future myocardial infarctions in women with
      baseline high versus baseline low levels of high-sensitivity C-reactive protein.
AB  - High-sensitivity C-reactive protein (hs-CRP) has previously been shown to be an
      independent predictor for the development of cardiovascular disease. However,
      little is known about the association between hs-CRP and the severity of
      cardiovascular events that occur. This study compared characteristics of incident
      myocardial infarctions (MIs) in 40 initially healthy women with very high
      baseline hs-CRP levels (>7.5 mg/L) with infarctions in 40 women with very low hs
      CRP levels (< or =1 mg/L). At baseline, very high hs-CRP was associated with a
      clinical diagnosis of hypertension, higher body mass index, lower high-density
      lipoprotein, and higher triglycerides. Our analysis found that the 2 study groups
      had similar proportions of ST-segment elevations on electrocardiograms, peak
      cardiac enzyme levels, postinfarct left ventricular function, and burden of
      coronary atherosclerosis seen on angiography. However, subjects with very high hs
      CRP levels developed infarctions significantly sooner than those with very low hs
      CRP levels (median time to event 4.45 vs 6.64 years, respectively, p <0.0001). In
      addition, higher baseline levels of hs-CRP were associated with significantly
      more fatal MIs (0% vs 4.6% vs 9.6% in subjects with hs-CRP levels <1, 1 to <3,
      and > or =3 mg/L, respectively, p for trend = 0.02). In conclusion, this study
      demonstrates that in initially healthy women high levels of hs-CRP predict
      earlier occurrence of MIs and a greater likelihood that infarctions will be
      fatal.

PMID- 17531570
TI  - Comparison of values of wide-range C-reactive protein to high-sensitivity C
      reactive protein in patients undergoing coronary angiography.
AB  - This study compared the recently introduced cheaper and more accessible wide
      range C-reactive protein (wr-CRP) with the commonly used high-sensitivity C
      reactive protein (hs-CRP) in patients undergoing coronary angiography. One
      hundred fifty-two consecutive patients who were admitted to a tertiary medical
      center and underwent angiography were included in the study. Arterial blood was
      obtained for the 2 assays at the beginning of angiography. A highly significant
      correlation (r = 0.983, p <0.001) was found between the 2 methods. This
      correlation was observed in different clinical scenarios and in different ranges
      of CRP. In conclusion, the real-time, online, and low-cost wr-CRP assay is a
      reasonable alternative to the Behring Dade hs-CRP method in the setting of stable
      and unstable coronary artery disease.

PMID- 17531571
TI  - Coronary circulation responses to binodenoson, a selective adenosine A2A receptor
      agonist.
AB  - The purpose of this study was to define binodenoson dosing regimens that produce
      coronary hyperemia comparable to those of adenosine and that are tolerated well
      by patients. An open-label, randomized, parallel-group, multicenter study
      enrolled adult patients who had completed diagnostic cardiac catheterization.
      Coronary blood flow velocity (CBFV) was measured with a Doppler flow wire, and
      CBFV reserve was determined before binodenoson administration. Patients (n = 133)
      received a 3-minute infusion of 0.3, 0.5, or 1 microg/kg/min or a bolus
      intravenous injection of 1.5 or 3 microg/kg. Coronary hyperemic responses were
      evident within seconds of administering binodenoson, and the magnitudes and
      durations of coronary hyperemic responses were dose related. The 1.5- and 3
      microg/kg doses, by infusion or bolus, produced maximal coronary hyperemia
      equivalent to CBFV reserve. All doses transiently decrease blood pressure and
      increased heart rate and rate-pressure product. In conclusion, the 1.5-microg/kg
      binodenoson bolus dose produced nearly maximal coronary hyperemia by 4.5 +/- 3.7
      minutes that was sustained for 7.4 +/- 6.86 minutes, was accompanied by modest
      changes in blood pressure, heart rate, and rate-pressure product, and produced no
      adverse changes on electrocardiogram, including no second- or third-degree
      atrioventricular block.

PMID- 17531572
TI  - Effect of anemia on hemorrhagic complications and mortality following
      percutaneous coronary intervention.
AB  - The relation across anemia, hemorrhagic complications, and mortality associated
      with percutaneous coronary intervention (PCI) is unclear. We reviewed the
      Randomized Evaluation in PCI Linking Angiomax to Reduced Clinical Events
      (REPLACE)-2 Trial, which compared bivalirudin plus provisional glycoprotein
      IIb/IIIa blockade with heparin plus planned glycoprotein IIb/IIIa blockade in
      patients undergoing urgent or elective PCI. Of the 6,010 patients randomized in
      REPLACE-2, 1,371 (23%) were anemic. Major bleeding was more common in anemic than
      in nonanemic patients (4.9% vs 2.8%, p = 0.0001). In anemic patients, treatment
      with bivalirudin (n = 678) resulted in a lower risk of major bleeding versus
      heparin plus glycoprotein IIb/IIIa blockade (n = 693, 3.5% vs 6.2%, p = 0.0221).
      Mortality was higher in anemic patients than in nonanemic patients at 30 days
      (0.9% vs 0.2%, p <0.0001), 6 months (2.6% vs 0.7%, p <0.0001), and 1 year (4.3%
      vs 1.5%, p <0.0001). There were no differences between anemic and nonanemic
      patients with regard to ischemic complications at 30 days. Although anemic
      patients had higher mortality rates, proportions of cardiovascular and
      noncardiovascular mortalities were equal in anemic and nonanemic patients. In
      conclusion, anemic patients undergoing PCI have an increased risk of mortality
      and major bleeding, but not of ischemic events, and the use of bivalirudin with
      provisional glycoprotein IIb/IIIa blockade decreases the risk of hemorrhagic
      complications compared with heparin plus planned glycoprotein IIb/IIIa blockade.

PMID- 17531573
TI  - Measuring aspirin resistance, clopidogrel responsiveness, and postprocedural
      markers of myonecrosis in patients undergoing percutaneous coronary intervention.
AB  - Aspirin and clopidogrel are proven to prevent thromboembolic events during
      percutaneous coronary intervention (PCI). Enzyme release of creatine kinase-MB
      (CK-MB) enzyme during PCI has been associated with an increased risk of future
      adverse cardiac events. This study examined the correlation between measurements
      of aspirin resistance and the level of inhibition of the thienopyridine-specific
      P2Y12 platelet receptor and CK-MB release after PCI. We prospectively studied 330
      patients with elective PCI treated with drug-eluting stents. Patients were
      pretreated with aspirin and clopidogrel. Patients with positive CK-MB or acute
      coronary syndrome and those on glycoprotein IIb/IIIa inhibitors were excluded.
      Serum assays of aspirin resistance (Ultegra Rapid Platelet Function Assay-ASA,
      Accumetrics) and clopidogrel resistance (Rapid Platelet Function Assay P2Y12,
      Accumetrics) were performed before PCI. Serum troponinI and CK-MB levels were
      measured at 8, 16, and 24 hours after PCI. Aspirin resistance unit (ARU)
      measurement > or =550 was detected in 12 patients (3.7%). Mean platelet
      reactivity unit (PRU; measurement of inhibition of P2Y12 activity) was 192.2 +/-
      95.4 (lower PRU, more inhibition of P2Y12 receptor). There was no correlation
      between level of ARU or PRU and troponin I or CK-MB release after PCI at any time
      point. Only multivessel coronary disease was found to be a predictor of any
      increase in CK-MB in a multivariate analysis (odds ratio 2.2, 95% confidence
      interval 1.4 to 3.3, p = 0.0003). A positive correlation was found between levels
      of ARU and PRU. Target vessel revascularization/major adverse cardiac event rate
      at 6 months was 8.2% with no correlation between ARU or PRU and release of
      cardiac enzymes or occurrence of adverse cardiac events. In conclusion, this
      study does not support routine measurements of aspirin and clopidogrel resistance
      in stable patients undergoing PCI.

PMID- 17531574
TI  - Effect of early statin treatment at standard doses on long-term clinical outcomes
      in patients with acute myocardial infarction (the Heart Institute of Japan,
      Department of Cardiology Statin Evaluation Program).
AB  - Long-term preventive effects of standard statin therapy in patients with acute
      myocardial infarction (AMI) against a secondary cardiac event remain unclear. The
      aims of this study were to evaluate and clarify characteristics of patients with
      AMI in whom standard statin therapy has beneficial effects against a secondary
      event in a real-world setting. Between 1999 and 2004, 4,075 patients with AMI
      were registered and followed prospectively, of whom 1,404 (matched by propensity
      scores) were analyzed. Statin use was defined as prescription on discharge from
      the hospital, and the control group was not prescribed statins at discharge. The
      primary end point was total mortality rate. Final follow-up was performed in June
      2006 (median 4.1 years), and follow-up rate was 97.2%. During follow-up, 139
      patients died, including 87 (12.4%) from the control group and 52 (7.4%) from the
      statin group. The hazard ratio for statin therapy was 0.64 (95% confidence
      interval 0.45 to 0.90, p = 0.011) throughout the study. Early statin therapy was
      strongly correlated with a lower risk of cardiovascular death, less recurrence of
      AMI, and less heart failure. Statin therapy was particularly beneficial for men,
      patients > or =60 years of age, and patients with a high low-density lipoprotein
      cholesterol level > or =155 mg/dl. In conclusion, these findings suggest that
      initiating standard rather than intensive statin therapy immediately after AMI
      decreases long-term mortality and subsequent cardiac events.

PMID- 17531575
TI  - Comparison of multidetector 64-slice computed tomographic angiography to coronary
      angiography to assess the patency of coronary artery bypass grafts.
AB  - This study prospectively evaluated the diagnostic accuracy of 64-slice computed
      tomographic angiography (CTA) in assessing the patency of coronary artery bypass
      grafts compared with invasive coronary angiography. In total 147 bypass grafts
      (100 venous grafts and 47 mammary artery grafts) were evaluated in 50 consecutive
      patients. Contrast-enhanced 64-slice CTA was performed and compared with invasive
      angiography. The computed tomographic angiographic scan protocol used 64- x 0.5
      mm slice collimation and 0.33-second gantry rotation time during simultaneous
      electrocardiographic gating. Patients with a heart rate >65 beats/min received
      beta blockers. Overall 145 of 147 bypass grafts (98.6%) were detected by CTA; 2
      nonvisualized grafts were occluded at the time of invasive angiography. Of the
      grafts visualized, 28 were totally occluded, 103 were patent, and 14 had
      significant stenoses that were confirmed by invasive angiography. Ninety-five
      percent (111 of 117) of patent grafts demonstrated good run-off distal to
      anastomoses but without an ability to accurately evaluate the presence of
      retrograde flow; 83% (97 of 117) of distal anastomoses were adequately evaluated,
      whereas the remaining 17% (20 of 117) were not well visualized due to vascular
      clips and/or calcification artifacts. Two grafts were not demonstrated by
      invasive angiography but were detected by CTA and found to be widely patent. In
      conclusion, multidetector 64-slice CTA is a valuable tool for direct
      visualization of coronary bypass grafts and assessment of their patency.
      Dysfunctional bypass grafts can be detected with high diagnostic accuracy.

PMID- 17531576
TI  - Relation of aortic valve calcium to myocardial ischemic perfusion in individuals
      with a low coronary artery calcium score.
AB  - The absence of coronary artery calcium (CAC) is associated with minimal
      atherosclerosis. Nonetheless, morbid and mortal cardiovascular events occur in
      patients with low CAC. This study attempts to identify whether calcific deposits
      outside the coronary arteries or traditional cardiovascular risk variables are
      associated with myocardial ischemia in patients with low CAC scores. From 1998 to
      2006, a total of 605 patients with an Agatston CAC score of 0 to 10 were referred
      for stress echocardiography or myocardial perfusion imaging. There was a low rate
      (1.2%) of myocardial ischemia. Seven of 303 patients (2.3%) had ischemia on
      perfusion imaging. Zero of 302 stress echocardiograms were abnormal. Traditional
      risk-factor analysis did not predict the presence of ischemia. No differences in
      age, gender, or self-reported hyperlipidemia, diabetes mellitus, tobacco use,
      hypertension, or family history of premature heart disease were noted. Contrary
      to previous belief, patients with myocardial ischemia were not younger or female.
      Aortic valve calcium (AVC) was associated with ischemia (p = 0.02), with a >10
      fold likelihood of having ischemia detected by MPS versus those without AVC
      (20.0% vs 1.7%). In conclusion, a CAC score <10 is associated with a low rate of
      myocardial ischemia. AVC may identify a subset of patients who may be at higher
      risk.

PMID- 17531577
TI  - Comparison of rosuvastatin versus atorvastatin in South-Asian patients at risk of
      coronary heart disease (from the IRIS Trial).
AB  - In a large randomized trial of statin therapy in patients of South-Asian origin
      with hypercholesterolemia, 740 patients in the United States and Canada received
      6 weeks of treatment with rosuvastatin 10 or 20 mg or atorvastatin 10 or 20 mg. A
      total of 485 patients (66%) were categorized as being at high risk of coronary
      heart disease and had a National Cholesterol Education Program Adult Treatment
      Panel III treatment goal of low-density lipoprotein (LDL) cholesterol <100 mg/dl
      (<2.6 mmol/L). LDL cholesterol decreased by 45% with rosuvastatin 10 mg versus
      40% with atorvastatin 10 mg (p = 0.0023) and by 50% with rosuvastatin 20 mg
      versus 47% with atorvastatin 20 mg (p = NS). National Cholesterol Education
      Program Adult Treatment Panel III LDL cholesterol goal achievement rates in high
      risk patients (all patients) were 76% (79%) and 88% (89%) with rosuvastatin 10
      and 20 mg, respectively, compared with 70% (76%) and 81% (85%) with atorvastatin
      10 and 20 mg, respectively. Rosuvastatin and atorvastatin were well tolerated.
      There were no clinically relevant differences between statins in adverse events
      or incidence of creatine kinase >10 times the upper limit of normal, alanine
      aminotransferase >3 times the upper limit of normal on 2 consecutive occasions,
      or proteinuria or hematuria over the relatively short duration of treatment. In
      conclusion, statin therapy was well tolerated and effective in decreasing LDL
      cholesterol in patients of South-Asian origin, with the 10- and 20-mg doses of
      rosuvastatin and atorvastatin allowing most patients to reach recommended LDL
      cholesterol goals.

PMID- 17531578
TI  - Effect of candesartan and various inflammatory markers on maintenance of sinus
      rhythm after electrical cardioversion for atrial fibrillation.
AB  - Inflammatory markers, their relation to maintenance of sinus rhythm after
      electrical cardioversion for atrial fibrillation (AF), and the effect of
      candesartan were investigated in a double-blind placebo-controlled study
      (CAPRAF). One hundred seventy-one patients with persistent AF were randomly
      assigned to receive candesartan 8 mg/day or placebo for 3 to 6 weeks before and
      candesartan 16 mg/day or placebo for 6 months after electrical cardioversion.
      Serum levels of high-sensitivity C-reactive protein (hs-CRP), tumor necrosis
      factor-alpha, interleukin-6, P-selectin, E-selectin, CD-40 ligand, and vascular
      cell adhesion molecule-1 were measured at baseline and end of study. Compared
      with patients with a relapse of AF, patients still in sinus rhythm at 6 months
      after cardioversion (n = 40) had lower baseline hs-CRP and E-selectin levels:
      median 2.36 mg/L (25th, 75th percentiles 1.28, 4.09) versus 3.44 mg/L (25th, 75th
      percentiles 1.66, 6.05, p = 0.031) and 32 ng/ml (25th, 75th percentiles 23, 42)
      versus 37 ng/ml (25th, 75th percentiles 28, 51, p = 0.042), respectively. Neither
      sustained sinus rhythm for 6 months nor treatment with candesartan had an impact
      on measured concentrations of markers of inflammation. In conclusion, low hs-CRP
      and E-selectin at baseline were associated with maintenance of sinus rhythm after
      electrical cardioversion.

PMID- 17531579
TI  - Factors influencing blood pressure response to trandolapril add-on therapy in
      patients taking verapamil SR (from the International Verapamil SR/Trandolapril
      [INVEST] Study).
AB  - Factors such as age and race/ethnicity might influence blood pressure (BP)
      response to drugs. Therapeutic response to the angiotensin-converting enzyme
      inhibitor trandolapril used as add-on therapy to stable calcium channel blocker
      therapy with verapamil sustained release 240 mg was addressed in a
      racially/ethnically diverse group of 1,832 hypertensive patients with coronary
      artery disease. Furthermore, the association with a polymorphism (1166A-->C) in
      the angiotensin II type 1 receptor gene (AGTR1) was tested. BP response was
      compared between groups using analysis of covariance after adjustment for
      covariates associated with BP response. Genotyping was performed using polymerase
      chain reaction and pyrosequencing. Trandolapril decreased mean unadjusted
      systolic and diastolic BPs by -9.1 +/- 17.3 (SD) and -4.1 +/- 10.1 mm Hg,
      respectively. The percentage of patients with BP under control (<140/90 mm Hg)
      increased from 6.7% to 41.3% (p <0.0001). Adjusted BP response was significantly
      associated with age and baseline systolic and diastolic BP (p <0.0001). Whereas
      the decrease in systolic BP was more pronounced in younger patients, the opposite
      was observed for diastolic BP decrease. Diastolic BP response was also
      significantly associated with race. Specifically, the adjusted diastolic BP
      decrease was significantly smaller in Hispanics and blacks than whites (p =
      0.0032 and p = 0.0069, respectively). However, Hispanics achieved a decrease in
      systolic BP and an increase in BP control similar to the other ethnic groups.
      There was no genetic association between AGTR1 1166A-->C genotype and BP
      response. In conclusion, trandolapril add-on therapy was effective in increasing
      BP control, with age and baseline BP associated with both systolic and diastolic
      BP response. Race was associated with diastolic BP response, although the
      difference is likely not to be clinically significant and AGTR1 genotype was not
      associated with BP response.

PMID- 17531580
TI  - Value of myocardial viability estimation using dobutamine stress echocardiography
      in assessing risk preoperatively before noncardiac vascular surgery in patients
      with left ventricular ejection fraction <35%.
AB  - Patients with heart failure (HF) scheduled for vascular surgery have an increased
      risk of adverse postoperative outcome, and stratification usually depends on
      dichotomous risk factors. A quantitative prognostic model for patients with HF
      was developed using wall motion patterns during dobutamine stress
      echocardiography (DSE). A total of 295 consecutive patients (mean age 67 +/- 12
      years) with ejection fraction < or =35% were studied. During DSE, wall motion
      patterns of dysfunctional segments were scored as scar, ischemia, or sustained
      improvement. Cardiac death and myocardial infarction were noted perioperatively
      and during 5 years of follow-up. Of 4,572 dysfunctional segments; 1,783 (39%) had
      ischemia, 1,280 (28%) had sustained improvement, and 1,509 (33%) had scar. In 212
      patients, > or =1 ischemic segment was present; 83 had only sustained
      improvement. Perioperative and late cardiac event rates were 20% and 30%,
      respectively. Using multivariate analysis, number of ischemic segments was
      associated with perioperative cardiac events (odds ratio per segment 1.6, 95%
      confidence interval 1.05 to 1.8), whereas number of segments with sustained
      improvement was associated with improved outcome (odds ratio per segment 0.2, 95%
      confidence interval 0.04 to 0.7). Multivariate independent predictors of late
      cardiac events were age and ischemia. Sustained improvement was associated with
      improved survival. In conclusion, DSE provides accurate risk stratification of
      patients with HF undergoing vascular surgery.

PMID- 17531581
TI  - The editor's roundtable: Acute decompensated heart failure.

PMID- 17531582
TI  - Effect of metoprolol on heart rate variability in symptomatic patients with
      mitral valve prolapse.
AB  - Metoprolol is widely used to eliminate symptoms in patients with mitral valve
      prolapse (MVP), a condition associated with enhanced sympathetic tone. In this
      study, effects of metoprolol on heart rate variability (HRV) indices were
      investigated in symptomatic patients with MVP. Thirty-nine symptomatic patients
      with MVP (26 women, mean age 26 +/- 7 years) and 16 age- and gender-matched
      controls were studied. After a baseline 24-hour Holter evaluation in all
      subjects, patients with MVP were started on metoprolol succinate therapy at a
      dose of 25 to 100 mg/d, and Holter analysis was repeated at the end of 3 months
      of metoprolol therapy. At the basal evaluation, all time-domain HRV indices with
      the exception of proportion of adjacent RR intervals differing by >50 ms in the
      24-hour recording were significantly lower in patients with MVP than controls (SD
      of all normal-to-normal [NN] intervals, p = 0.013; SD of average NN intervals
      calculated during 5-minute periods of the entire recording, p = 0.03; triangular
      index, p = 0.025; and square root of mean squared differences in successive NN
      intervals, p = 0.026). After metoprolol treatment, all HRV indices significantly
      improved compared with baseline (SD of all NN intervals, p = 0.028; SD of average
      NN intervals calculated during 5-minute periods of the entire recording, p =
      0.043; triangular index, p = 0.004; square root of the mean squared differences
      in successive NN intervals, p = 0.021; and proportion of adjacent RR intervals
      differing by >50 ms in the 24-hour recording, p = 0.014), and HRV indices after
      metoprolol treatment were similar to those of the control group (p >0.05). In
      conclusion, metoprolol significantly improved impaired HRV parameters in
      symptomatic patients with MVP.

PMID- 17531583
TI  - Comparison of long-term outcome after mitral valve replacement or repeated
      balloon mitral valvotomy in patients with restenosis after previous balloon
      valvotomy.
AB  - Symptomatic mitral stenosis (MS) develops in 7% to 21% of patients after
      percutaneous mitral balloon valvotomy (PMV). Treatment options for these patients
      are surgical mitral valve replacement (MVR) or repeated PMV. However, no
      comparisons were made between these 2 procedures regarding long-term outcome.
      This retrospective study compares the long-term outcome of 888 patients with
      symptomatic MS after MVR or repeated PMV who underwent PMV from April 1988 to
      December 2003. Thirty-two patients subsequently underwent repeated PMV, and 59
      patients underwent MVR for symptomatic MS. Mean follow-up was 85 +/- 43 months
      with a maximum follow-up of 15 years. Patients with MVR have more unfavorable
      clinical characteristics, including a higher incidence of atrial fibrillation and
      severe mitral regurgitation. Event-free survival was similar between the 2 groups
      up to 40 months after the procedure; 3-year event-free survival rates were 96.6%
      for MVR patients and 90.0% for repeated PMV patients (p = 0.215). However, after
      40 months, the outcome was more favorable for MVR. Comparing MVR versus PMV, 6
      year event-free survival rates were 93.0% versus 75.9% (p = 0.036), and 9-year
      event-free survival rates were 90.4% versus 36.0% (p <0.001). In conclusion, the
      long-term outcome of patients with symptomatic MS after previous PMV was more
      favorable after MVR than after repeated PMV. These data suggest that MVR may be
      the preferred mode of therapy in patients with unfavorable valve morphologic
      characteristics and no co-morbid disease.

PMID- 17531584
TI  - Usefulness and safety of transcatheter ablation of atrial fibrillation in
      patients with hypertrophic cardiomyopathy.
AB  - Atrial fibrillation (AF) is common in patients with hypertrophic cardiomyopathy
      (HC) and predicts adverse outcome. Radiofrequency catheter ablation (RFCA)
      represents a potentially advantageous alternative to lifelong pharmacologic
      treatment. However, its efficacy in patients with HC is not established. In the
      present study, the feasibility, safety, and efficacy of RFCA of AF in patients
      with HC were evaluated. Twenty-six patients with HC with paroxysmal (n = 13) or
      permanent (n = 13) AF refractory to antiarrhythmic therapy (age 58 +/- 11 years,
      time from AF onset 7.3 +/- 6.2 years, left atrial volume 170 +/- 48 ml) underwent
      RFCA. A schema with pulmonary vein isolation plus linear lesions was used. No
      major periprocedural complication occurred. One patient died from a hemorrhagic
      stroke 4 weeks after RFCA while in sinus rhythm. During a 19 +/- 10-month follow
      up, 9 of the remaining 25 patients (36%) experienced recurrence of AF (despite
      repeated RFCA in 3) and were considered failures, whereas 16 remained in sinus
      rhythm (i.e., 64% overall success rate). Ten of these 16 patients were off
      antiarrhythmic drug therapy at final evaluation. RFCA was highly successful in
      patients with paroxysmal AF (77% success rate compared with 50% in the subgroup
      with permanent AF). Patients with restoration of sinus rhythm showed marked
      symptomatic improvement (final New York Heart Association functional class 1.2 +/
      0.5 vs 1.7 +/- 0.7 before the procedure, p = 0.003). Conversely, patients for
      whom RFCA failed showed no change (final functional class 1.9 +/- 0.8 vs 1.7 +/-
      0.9 before the procedure, p = 0.59). In conclusion, in most studied patients with
      HC, RFCA proved a safe and effective therapeutic option for AF, improved
      functional status, and was able to reduce or postpone the need for long-term
      pharmacologic treatment.

PMID- 17531585
TI  - Effect of chronic afterload increase on left ventricular myocardial function in
      patients with congenital left-sided obstructive lesions.
AB  - The effect of pressure-overloading distance on left ventricular (LV) function in
      patients with congenital aortic coarctation and aortic stenosis (AS) was
      investigated. LV long-axis motions were recorded using M-mode and tissue Doppler
      imaging (TDI) techniques in 46 consecutive patients with severe LV outflow tract
      obstruction (23 coarctation and 23 AS), and results were compared with those of
      23 controls. TDI lateral and septal long-axis systolic velocities, early
      diastolic velocities, and M-mode systolic amplitudes were lower in patients with
      coarctation and AS than controls (lateral site long-axis systolic velocity 7.1 +/
      1.7 and 6.4 +/- 1.6 vs 9.7 +/- 1.7 cm/s, septal site long-axis systolic velocity
      6.3 +/- 1.3 and 5.4 +/- 1.1 vs 7.7 +/- 1.3 cm/s; lateral site early diastolic
      velocity 10.5 +/- 2.2 and 8.2 +/- 2.6 vs 13.1 +/- 2.5 cm/s, septal site early
      diastolic velocity 7.4 +/- 1.9 and 6.0 +/- 1.8 vs 10.8 +/- 1.6 cm/s, lateral site
      M-mode systolic amplitude 1.4 +/- 0.2 and 1.3 +/- 0.2 vs 1.6 +/- 0.2 cm, septal
      site M-mode systolic amplitude 1.2 +/- 0.2 and 1.1 +/- 0.2 vs 1.4 +/- 0.2 cm, p
      <0.01 for all). Compared with patients with coarctation, those with AS had lower
      TDI velocities, higher early LV filling velocity/long-axis diastolic velocity
      ratios, and a higher prevalence of long-axis incoordination (p <0.05 for all)
      despite similar LV mass index, ejection fraction, and systolic wall stress. In
      conclusion, LV long-axis function is impaired in patients with a chronic increase
      in afterload. Worse deterioration in LV function and higher prevalence of long
      axis incoordination independent of LV outflow resistance is seen in patients with
      proximally increased LV afterload (AS) compared with distal disease (aortic
      coarctation).

PMID- 17531586
TI  - Frequency of development of aortic cuspal prolapse and aortic regurgitation in
      patients with subaortic ventricular septal defect diagnosed at <1 year of age.
AB  - The natural history of aortic cuspal prolapse and aortic regurgitation (AR),
      studied most commonly in subpulmonic ventricular septal defect (VSD), has not
      been well defined in isolated, unrepaired VSD diagnosed during infancy. This
      study aimed to define the incidence and progression of aortic cuspal prolapse and
      AR in patients with subaortic VSDs diagnosed at <1 year of age who had no aortic
      cuspal prolapse or AR at presentation and did not require surgery within the
      first year of life. Patients had yearly follow-up, and data regarding clinical
      course, physical examination, and echocardiography were obtained. Comparisons
      were made between patients who developed aortic cuspal prolapse and AR and those
      who did not. One hundred patients, with a mean age at VSD diagnosis of 0.1 +/-
      0.5 years, followed for a mean of 7.1 +/- 10.1 years, were studied. Aortic cuspal
      prolapse developed in 14 patients (14%) at a mean age of 7.1 +/- 6 years (range
      0.4 to 18.4). AR murmurs were heard in 6 patients (6%) at a mean age of 5.1 +/-
      3.1 years, all of whom had aortic cuspal prolapse and underwent VSD closure and
      aortic valvuloplasty. In conclusion, aortic cuspal prolapse and clinical AR are
      not uncommon in patients with subaortic VSDs. Long-term follow-up of patients
      with subaortic VSDs should include the serial evaluation of aortic valve anatomy
      and function.

PMID- 17531587
TI  - Comparison of echocardiographic and cardiac magnetic resonance imaging for
      assessing right ventricular function in adults with repaired tetralogy of fallot.
AB  - Adults with repaired tetralogy of Fallot and significant chronic pulmonary
      regurgitation are at risk for progressive right ventricular (RV) dilatation and
      dysfunction. The assessment of RV function is important in the management in
      these patients. There is still a lack of an adequate geometric model to quantify
      RV function by echocardiography. The myocardial performance index (MPI) is a
      nonvolumetric method to quantify global ventricular function. In this study, the
      accuracy of MPI obtained by echocardiography to quantify RV function was assessed
      in 57 adults with repaired tetralogy of Fallot. The MPI measurement was compared
      with the RV ejection fraction (EF) derived by cardiac magnetic resonance imaging.
      There was a negative linear correlation between the MPI and the RVEF (r = 0.73, p
      <0.001). A MPI cutoff of > or =0.40 had a sensitivity of 81% and a specificity of
      85% to diagnose a RVEF <35%. A MPI cutoff of <0.25 had a sensitivity of 70% and a
      specificity of 89% to identify patients with RVEFs > or =0.50. In a multivariate
      regression model, the MPI was not affected by the degree of pulmonary
      regurgitation, the presence of tricuspid regurgitation, or the QRS duration. In
      conclusion, the Doppler-derived MPI is a simple and reliable method for the
      evaluation of RV systolic function in adults with repaired tetralogy of Fallot.

PMID- 17531588
TI  - Association of multiple inflammatory markers with carotid intimal medial
      thickness and stenosis (from the Framingham Heart Study).
AB  - Inflammatory markers, particularly C-reactive protein (CRP), predict incident
      cardiovascular disease and are associated with the presence of subclinical
      atherosclerosis. The relations between multiple inflammatory markers and direct
      measures of atherosclerosis are less well established. Participants in the
      Offspring Cohort of the Framingham Heart Study (n = 2,885, 53% women, mean age 59
      years) received routine assessments of common carotid artery intima-media
      thickness (CCA-IMT), internal carotid artery intima-media thickness (ICA-IMT),
      and the presence or absence of > or =25% carotid stenosis by ultrasonography.
      Circulating inflammatory markers assessed from an examination 4 years later
      included CRP, interleukin-6 (IL-6), intercellular adhesion molecule-1, monocyte
      chemoattractant protein-1, P-selectin, and CD40 ligand. Assessed as a group,
      inflammatory markers were significantly associated with ICA-IMT (p = 0.01),
      marginally with carotid stenosis (p = 0.08), but not with CCA-IMT. Individually,
      with an increase from the 25th to 75th percentile in IL-6, there were significant
      increases in ICA-IMT and carotid stenosis (for ICA-IMT, estimated fold increase
      1.04, 95% confidence interval 1.03 to 1.06, p = 0.0004; for carotid stenosis,
      odds ratio 1.25, 95% confidence interval 1.06 to 1.47, p = 0.007) after
      adjustment for age, gender, and established risk factors for atherosclerosis.
      There was a similar significant multivariate-adjusted association of CRP with ICA
      IMT but not with carotid stenosis. Smoking appeared to modify the associations of
      ICA-IMT with CRP (p = 0.009) and with IL-6 (p = 0.006); the association was more
      pronounced in current (vs former or never) smokers. In conclusion, there were
      modest associations of inflammatory markers, particularly IL-6, with carotid
      atherosclerosis. This association appears more pronounced in current smokers than
      in former smokers and nonsmokers.

PMID- 17531589
TI  - Changes in coronary anatomy and physiology after heart transplantation.
AB  - Cardiac allograft vasculopathy (CAV) is a progressive process involving the
      epicardial and microvascular coronary systems. The timing of the development of
      abnormalities in these 2 compartments and the correlation between changes in
      physiology and anatomy are undefined. The invasive evaluation of coronary artery
      anatomy and physiology with intravascular ultrasound, fractional flow reserve,
      coronary flow reserve, and the index of microcirculatory resistance (IMR) was
      performed in the left anterior descending coronary artery during 151 angiographic
      evaluations of asymptomatic heart transplant recipients from 0 to >5 years after
      heart transplantation (HT). There was no angiographic evidence of significant
      CAV, but during the first year after HT, fractional flow reserve decreased
      significantly (0.89 +/- 0.06 vs 0.85 +/- 0.07, p = 0.001), and percentage plaque
      volume derived by intravascular ultrasound increased significantly (15.6 +/- 7.7%
      to 22.5 +/- 12.3%, p = 0.0002), resulting in a significant inverse correlation
      between epicardial physiology and anatomy (r = -0.58, p <0.0001). The IMR was
      lower in these patients compared with those > or =2 years after HT (24.1 +/- 14.3
      vs 29.4 +/- 18.8 units, p = 0.05), suggesting later spread of CAV to the
      microvasculature. As the IMR increased, fractional flow reserve increased (0.86
      +/- 0.06 to 0.90 +/- 0.06, p = 0.0035 comparing recipients with IMRs < or =20 to
      those with IMRs > or =40), despite no difference in percentage plaque volume
      (21.0 +/- 11.2% vs 20.5 +/- 10.5%, p = NS). In conclusion, early after HT,
      anatomic and physiologic evidence of epicardial CAV was found. Later after HT,
      the physiologic effect of epicardial CAV may be less, because of increased
      microvascular dysfunction.

PMID- 17531590
TI  - Incidental detection of cancers and other non-cardiac abnormalities on coronary
      multislice computed tomography.
AB  - The investigators prospectively examined 625 consecutive patients who underwent
      coronary multislice computed tomography (MSCT) for suspected coronary artery
      disease (CAD) and evaluated the presence or absence of cancers and other
      noncardiac abnormalities on the original transverse sectional images of MSCT.
      Eight patients with known cancers were excluded from the analysis. The remaining
      617 patients (344 men, 273 women; mean age 66 +/- 12 years) were analyzed.
      Cancers were found in 7 patients (1.13%) on the multislice computed tomographic
      images, including 4 lung cancers (0.65%), 2 thyroid cancers (0.32%), and 1
      hepatic cancer (0.16%). In addition, nonmalignant abnormalities (nodules, tumors,
      or lymphadenopathies) were also found in 142 patients (23.01%), consisting of 58
      postinflammatory lung nodules (9.40%), 49 hepatic cysts or hemangiomas (7.94%),
      18 benign thyroid tumors (2.92%), 12 mediastinal lymphadenopathies (1.94%), 4
      benign mammary gland tumors (0.65%), and 1 esophageal submucosal tumor (0.16%).
      In conclusion, cancers and other noncardiac abnormalities are often found in
      patients who undergo coronary MSCT for suspected CAD. Because patients who
      undergo coronary MSCT for suspected CAD are mostly elderly and therefore may have
      unrecognized cancers or other noncardiac abnormalities, care should thus be taken
      not to overlook these abnormalities when analyzing the multislice computed
      tomographic images.

PMID- 17531591
TI  - Relation between depressive symptoms and common carotid artery atherosclerosis in
      American persons > or =65 years of age.
AB  - Few epidemiologic studies have examined the association between depressive
      symptoms and atherosclerosis in subjects aged > or =65 years. Most of these
      studies were cross sectional and could not determine the temporality between
      depressive symptoms and the development of abnormal common carotid artery (CCA)
      intima-media thickness (CCA-IMT). To investigate the association between
      depressive symptoms and CCA atherosclerosis in subjects aged > or =65 years, data
      from 3,781 participants aged > or =65 years from the Cardiovascular Health Study
      were analyzed. The presence of depressive symptoms was measured by the Center for
      Epidemiologic Studies Depression Scale, while CCA-IMT as an indicator of CCA
      atherosclerosis was measured by B-mode carotid ultrasonography. Multivariate
      generalized estimation equations adjusted for age, gender, race, alcohol intake,
      blood glucose status, body mass index, and time showed that subjects aged > or
      =65 years with depressive symptoms had larger CCA-IMTs than those who did not
      have such symptoms (beta = 18.26 microm, SE 8.06, p = 0.03). Using 1,000 and
      1,140 microm as cut-off points to exclude participants who had abnormal CCA-IMTs
      at baseline, the adjusted relative risks and the corresponding 95% confidence
      intervals of developing abnormal CCA-IMT over 3 years were 1.30 (95% confidence
      interval 1.10 to 1.44) and 1.21 (95% confidence interval 1.00 to 1.46),
      respectively. Similar results were obtained after excluding participants with
      prevalent cardiovascular disease at baseline. In conclusion, these data indicate
      that depressive symptoms are associated with the development of atherosclerosis
      in subjects aged > or =65 years.

PMID- 17531592
TI  - A comparison by medicine residents of physical examination versus hand-carried
      ultrasound for estimation of right atrial pressure.
AB  - Physicians' ability to accurately estimate right atrial (RA) pressure from
      bedside evaluation of the jugular venous waveform is poor, particularly when
      performed by physicians in training. Conventional ultrasound measurement of the
      inferior vena cava (IVC) accurately predicts RA pressure, but the cost, lack of
      portability, and specialized training required to acquire and interpret the data
      render this modality impractical for routine clinical use. The objective of this
      study was to compare physical examination with hand-carried ultrasound (HCU) in
      the detection of elevated RA pressure (>10 mm Hg). After limited training (4
      hours didactic and 20 studies), 4 internal medicine residents using an HCU device
      estimated RA pressure from images of the IVC in 40 consecutive patients <1 hour
      after right-sided cardiac catheterization. RA pressure was also estimated from
      examination of the jugular venous pulse (JVP) in 40 patients before right-sided
      cardiac catheterization. RA pressure was successfully estimated from HCU images
      of the IVC in 90% of patients, compared with 63% from JVP examination. The
      sensitivity for predicting RA pressure >10 mm Hg was 82% with HCU and 14% from
      JVP inspection. Specificities were similar between the techniques. Overall
      accuracies were 71% using HCU and 60% with JVP assessment. In conclusion,
      internal medicine residents with brief training in echocardiography can more
      frequently and more accurately predict elevated RA pressure using HCU
      measurements of the IVC than with physical examination of the JVP.

PMID- 17531593
TI  - Cardioversion for atrial fibrillation: does inflammation matter?

PMID- 17531594
TI  - A new generation of coronary vasodilators in stress perfusion imaging.

PMID- 17531595
TI  - Can multislice computed tomography in an asymptomatic high-risk population really
      impact on therapeutic decision-making?

PMID- 17531597
TI  - Alcohol-induced hypertension--just how much of a cardiovascular risk factor?

PMID- 17531598
TI  - Proceedings of the Fifth International Symposium on Intrauterine Devices and
      Systems for Women's Health. October 27-28, 2006. New York, New York, USA..

PMID- 17531599
TI  - Antiprogestin-releasing intrauterine devices: a novel approach to endometrial
      contraception.
AB  - Intrauterine devices (IUDs) that release progestins are highly effective
      contraceptives, but they induce breakthrough bleeding that some women find
      unacceptable. Because progesterone (P) antagonists [antiprogestins (APs)] are
      known to suppress the endometrium, induce amenorrhea and inhibit fertility, AP
      releasing IUDs (AP-IUDs) may provide an effective contraceptive that also
      controls endometrial bleeding. Here, we assessed the effects of empty (blank) vs.
      AP-IUDs (ZK 230 211) on bleeding patterns and endometrial growth in
      ovariectomized, artificially cycled macaques. The AP-IUDs (but not the blank
      controls) induced extended, frank menstruation when inserted during the late
      luteal phase, an indication of local AP action. Over time, endometrial glandular
      and arterial proliferation were inhibited, steroid receptors were elevated,
      spiral arteries showed degenerative changes, P withdrawal bleeding was prevented,
      and estradiol (E(2))-dependent proliferation was suppressed by the AP-IUDs. In
      sum, AP-IUDs suppressed the effects of P on endometrial progestational
      development and blocked the effects of E(2) on endometrial proliferation, as
      previously shown for systemic treatment with APs. Therefore, AP IUDs may provide
      novel contraceptive devices with minimal breakthrough bleeding.

PMID- 17531600
TI  - The promise and reality of the intrauterine route for hormone delivery for
      prevention and therapy of gynecological disease.
AB  - CONTEXT: Progestins delivered by a variety of routes have been demonstrated, in
      addition to their high contraceptive effect, to have substantial benefits in the
      treatment of various gynecological disorders, and the intrauterine route has
      particular efficacy in treating endometrial and myometrial disorders. It should
      be possible to extend this to prevention of disease. THERAPY OF GYNECOLOGICAL
      DISEASE: Those conditions for which there is most evidence of therapeutic benefit
      from intrauterine release of progestins include heavy menstrual bleeding (due to
      most causes), endometrial hyperplasia, endometriosis and adenomyosis. PREVENTION
      OF GYNECOLOGICAL DISEASE: Reasonable evidence exists to support the findings that
      intrauterine levonorgestrel helps to prevent the development of uterine fibroids,
      endometriosis, endometrial hyperplasia, acute episodes of pelvic infection and a
      wide range of menstrual symptoms. There is also promise of prevention of
      endometrial carcinoma, endometrial polyps, infertility and perhaps adenomyosis.
      CONCLUSIONS: There is a need for specific studies to further explore the
      prevention of these gynecological conditions which can cause major health
      disturbances and community distress.

PMID- 17531601
TI  - Treatment of menorrhagia with an LNG-IUS.
AB  - Menorrhagia, also known as heavy menstrual bleeding, is defined as a menstrual
      blood loss is greater than 80 mL. The objective measurement of menorrhagia is not
      easy in clinical practice, but often, the subjective complaint correlates well
      with the measured loss. Four types of treatments - hysterectomy, endometrial
      resection or ablation, levonorgestrel-releasing intrauterine system (LNG-IUS) and
      oral medical therapy, are available for management of menorrhagia. The article
      reviews the efficacy of LNG-IUS on menorrhagia and compares it to other treatment
      methods.

PMID- 17531603
TI  - Levonorgestrel intrauterine system: bleeding disorders and anticoagulant therapy.
AB  - Hemostatic disorders in women are frequently associated with long-standing
      menorrhagia. This leads to significant morbidity and adversely affects quality of
      life. Management of these women poses a particular challenge; medical treatments
      may be contraindicated, and surgery carries additional risks. The levonorgestrel
      intrauterine system (LNG-IUS) has been shown to be highly efficacy in reducing
      menstrual blood loss in women with normal coagulation. It is also a reliable and
      reversible contraceptive. Data on the use of this system in women with bleeding
      disorders or those receiving anticoagulant therapy are limited. Analysis of data
      from four reported studies suggests that LNG-IUS is a viable and safe option for
      the management of menorrhagia in these women. Whether the underlying hemostatic
      disorders lead to a shorter duration of action or prolonged irregular
      bleeding/spotting post insertion is unknown and requires large prospective
      studies. Proper counselling remains crucial for patients' satisfaction.

PMID- 17531602
TI  - The levonorgestrel intrauterine system in nulliparous women.
AB  - The levonorgestrel intrauterine system (LNG-IUS) has been used internationally
      for over 15 years by 7 million women. Concern about providing the LNG-IUS to
      nulliparous women still exists, despite growing evidence of its safety and
      efficacy in this population. Expulsion rates do not vary by parity and, although
      evidence in nulliparas is scant, perforation rates are low in all women. Efficacy
      of the LNG-IUS is excellent regardless of parity, with less than 1 pregnancy per
      100 woman-years of use. Efficacy with immediate post-abortal insertion is also
      excellent and unvaried by parity. The presence of an LNG-IUS does not increase
      the risk of PID or infertility in either parous or nulliparous women and the LNG
      may be protective against infection. Acceptability is high in nulliparous women
      when compared either to parous LNG-IUS users or to nulliparous users of combined
      oral contraceptive pills. In conclusion, LNG-IUS is both safe and extremely
      efficacious for use in nulliparous women.

PMID- 17531604
TI  - Progestin-releasing intrauterine systems and leiomyoma.
AB  - Review of the existing published literature suggests that, in women with uterine
      fibroids, with or without menorrhagia, the high contraceptive efficacy of the
      levornorgestrel intrauterine system (LNG-IUS) remains intact. In such women, the
      LNG-IUS reduces menstrual blood loss and likely reduces menstrual pain. However,
      use of the LNG-IUS does not appear to reduce overall uterine dimensions or those
      of uterine fibroids. In women with uterine fibroids and menorrhagia, LNG-IUS
      expulsion rates may be somewhat higher than in women without fibroids. Although
      symptomatic relief is not guaranteed, these findings indicate that insertion of a
      LNG-IUS represents an appropriate therapeutic option for selected women with
      menstrual symptoms associated with uterine fibroids. Questions remain regarding
      the usefulness of routine preinsertion evaluation of the endometrial cavity as
      well as ultrasound-guided LNG-IUS insertion. Clinicians who candidly inform their
      patients regarding what we do and do not know regarding the benefits and risks of
      the LNG-IUS in women with fibroids should selectively make this therapy available
      prior to resorting to surgical therapies.

PMID- 17531605
TI  - Use of the levonorgestrel-releasing intrauterine system in women with
      endometriosis, chronic pelvic pain and dysmenorrhea.
AB  - OBJECTIVES: This report is a review of the medical literature on the use of the
      levonorgestrel-releasing intrauterine system (LNG-IUS) in women with
      endometriosis, adenomyosis, cyclic pelvic pain and dysmenorrhea. MATERIAL AND
      METHODS: A review was carried out using the MEDLINE and EMBASE databases to
      evaluate the use of LNG-IUS in women with endometriosis and adenomyosis. RESULTS:
      Nine studies were identified, only two of which were randomized clinical trials.
      One compared the insertion of LNG-IUS after surgery with expectant conduct and
      the other compared the use of the device with a GnRH analogue (GnRH-a). All
      studies reported an improvement in pelvic pain and dysmenorrhea, and a reduction
      in menstrual bleeding. One study found an improvement in the staging of the
      disease at 6 months of use, and the studies that evaluated the use of LNG-IUS in
      women with adenomyosis reported a reduction in uterine volume. Furthermore, the
      only study in which women were followed up for 3 years after insertion found
      improvement in pelvic pain at 12 months of use. However, there was no improvement
      after that period. CONCLUSIONS: The use of LNG-IUS is an alternative for the
      medical treatment of women suffering from endometriosis, adenomyosis, chronic
      pelvic pain or dysmenorrhea, but experience is limited and long-term studies are
      necessary to reach definitive conclusions. However, for women who do not wish to
      become pregnant, this device offers the possibility of at least 5 years of
      treatment following one single intervention.

PMID- 17531606
TI  - United States regulatory considerations for intrauterine progestins for hormone
      replacement therapy.
AB  - This paper presents information about U.S. Food and Drug Administration (FDA)
      considerations for intrauterine progestins as part of a hormone replacement
      therapy strategy. Current U.S.-approved intrauterine systems are reviewed as well
      as FDA formal guidance to industry regarding clinical evaluation of combination
      hormone products. The formal guidance is contrasted with FDA actions for approved
      combination products, and recommendations for proceeding with a development plan
      for an intrauterine delivery approach are discussed.

PMID- 17531607
TI  - Copper IUD and LNG IUS compared with tubal occlusion.
AB  - This article will cover current contraceptive use around the world, then examine
      the advantages and disadvantages of female sterilization, the hormonal
      intrauterine system and the copper intrauterine device. Finally, the need for
      contraceptive choice will be discussed along with a discussion on the cost
      effectiveness of these methods.

PMID- 17531608
TI  - The levonorgestrel-releasing intrauterine system as an alternative to
      hysterectomy in peri-menopausal women.
AB  - INTRODUCTION: Hysterectomy is one of the most common surgical procedures
      performed in gynecological practice, and the most common indication for
      hysterectomy is menorrhagia or excessive menstrual bleeding. Approximately 10-15%
      of fertile women have menorrhagia, defined as a menstrual blood loss (MBL) of >80
      mL. Since operative treatment in the form of a hysterectomy carries a not
      insignificant risk of morbidity and mortality, various forms of medical treatment
      have been advocated as initial treatment. RESULTS: Antifibrinolytic agents, e.g.,
      tranexamic acid (40-50% reduction), prostaglandin synthetase inhibitors (20-25%
      reduction), oral contraceptives (40-50%) and the intrauterine release of
      progestin with the levonorgestrel-releasing intrauterine system (LNG-IUS; 86-97%
      reduction), have all been shown to reduce MBL and to be effective in the
      treatment of idiopathic menorrhagia. In comparative and noncomparative trials,
      the greatest reduction in MBL has been achieved with the LNG-IUS. Thus, this
      system has been proposed as an alternative to hysterectomy in women with
      menorrhagia. In a randomized controlled trial, the LNG-IUS was compared with
      hysterectomy. Only 42% of the women randomized to the LNG-IUS system subsequently
      underwent a hysterectomy during the 5-year observation period, and the total
      costs (direct and indirect) were 40% lower with the LNG-IUS than with
      hysterectomy. CONCLUSION: Despite the strong evidence that medical treatment and,
      in particular, the LNG-IUS are effective, many hysterectomies and endometrial
      ablations/resections are performed annually without first evaluating medical
      treatment.

PMID- 17531609
TI  - The levonorgestrel intrauterine system for use in peri- and postmenopausal women.
AB  - The intrauterine system (IUS) delivering levonorgestrel (LNG; Mirena), initially
      developed as a long-acting method of contraception, has demonstrated its efficacy
      and safety in a large number of users all over the world. The local delivery of a
      small dose of a highly effective progestin in the uterine cavity maintains the
      endometrium in a nonproliferative state and reduces the number of bleeding days,
      thus preventing anemia, an important medical benefit, especially in developing
      countries. In addition, the intrauterine delivery of a progestin allows the
      treatment of other medical conditions and prevention of endometrial hyperplasia,
      in postmenopausal women receiving estrogen therapy. During the perimenopausal
      years, the IUS provides an effective contraception as occasional ovulations
      occur. In addition, by its direct effect on the endometrium, it prevents the
      occurrence of menorrhagia, a frequent condition in the premenopause. After
      cessation of the ovarian function, when estrogen therapy may be initiated, the
      IUS would ensure endometrial protection as a transition to the menopause and as
      long as hormone therapy is needed. Although the circulating levels of LNG are
      very low, minor side effects related to the androgenic properties of LNG have
      been reported. In addition, the insertion of the system needs a skilled health
      provider and may be difficult or painful when the uterus is small or atrophic.
      The development of smaller devices is warranted for these specific situations.

PMID- 17531610
TI  - Copper-T intrauterine device and levonorgestrel intrauterine system: biological
      bases of their mechanism of action.
AB  - All intrauterine devices (IUDs) that have been tested experimentally or
      clinically induce a local inflammatory reaction of the endometrium whose cellular
      and humoral components are expressed in the tissue and the fluid filling the
      uterine cavity. Depending on the reproductive strategy of the species considered
      and the anatomical features and physiologic mechanisms that characterize their
      reproductive system, the secondary consequences of this foreign body reaction can
      be very localized within the uterus, as in the rabbit, or widespread throughout
      the entire genital tract as in women or even systemic as in some farm animals.
      Levonorgestrel released from an IUD causes some systemic effects, but local
      effects such as glandular atrophy and stromal decidualization, in addition to the
      foreign body reaction, are dominant. Copper ions released from an IUD enhance the
      inflammatory response and reach concentrations in the luminal fluids of the
      genital tract that are toxic for spermatozoa. In the human, the entire genital
      tract appears affected due to luminal transmission of the noxa that accumulates
      in the uterine lumen. This affects the function and viability of gametes,
      decreasing the rate of fertilization and lowering the chances of survival of any
      embryo that may be formed, before it reaches the uterus. The bulk of the data
      indicate that if any embryos are formed in the chronic presence of an IUD, it
      happens at a much lower rate than in non-IUD users. The common belief that the
      usual mechanism of action of IUDs in women is destruction of embryos in the
      uterus is not supported by empirical evidence.

PMID- 17531611
TI  - Long-term use of the levonorgestrel-releasing intrauterine system.
AB  - Since its launch in Finland in 1990, the levonorgestrel-releasing intrauterine
      system (LNG IUS) has become available in more than 100 countries throughout the
      world, with most countries also having the approval for the treatment of
      idiopathic menorrhagia and protection from endometrial hyperplasia during
      estrogen replacement therapy. After its introduction in Finland and Scandinavian
      countries, the LNG IUS has been available in most European countries since the
      mid to late 1990s and in the United States since 2001. Studies on the repeat use
      of the LNG IUS with second and third consecutive IUSs have shown high
      continuation rates and low rates of adverse effects. During repeat use of the LNG
      IUS, the bleeding pattern changes toward an increasing amenorrhea rate. With
      regard to the menorrhagia indication, the 5-year follow-up results of a
      randomized comparative trial of the LNG IUS and hysterectomy have shown equal
      satisfaction and improvement in health-related quality of life with both
      treatments. Although a proportion of women assigned to the LNG IUS group
      eventually underwent hysterectomy, the continuation rate of the LNG IUS for
      menorrhagia is clearly superior to that of conventional medical therapy (e.g.,
      oral progestins). Use of the LNG IUS in combination with estrogen therapy in
      women undergoing menopausal transition seems to be well tolerated and associated
      with a favorable bleeding pattern.

PMID- 17531612
TI  - Worldwide use of intrauterine devices for contraception.
AB  - The intrauterine device is the most widely used reversible method of
      contraception in the world today, particularly in developing countries where it
      is used by 14.5% of women of reproductive age. In the developed world, this
      percentage is only 7.6%. There are marked regional differences with the highest
      use in Eastern Asia and the lowest in North America. Such differences between
      regions and countries can be explained by a number of factors at the individual,
      service delivery, program and policy levels. The situation in seven countries is
      briefly described to illustrate this and to conclude that this method of
      contraception is largely underutilized in many parts of the world, where it could
      play a significant role in improving women's health.

PMID- 17531613
TI  - Chinese experience with intrauterine devices.
AB  - Changes in the use of intrauterine devices (IUDs) for contraception in China in
      the past 10 years are reviewed. Replacement of the inert stainless steel ring
      with copper-bearing IUDs was an essential decision to improve the efficacy of the
      IUDs. The most commonly used, TCu380A, TCu220C and MLCu375, and those developed
      in China, such as the uterine-shaped UCu300 IUD and gamma Cu380 IUD, are
      reviewed. Studies of MLCu375 and TCu380A for emergency contraception revealed a
      highly effective method, which could prevent over 96% of unwanted pregnancies.
      Use of levonorgestrel-releasing system provides both contraceptive and
      therapeutic effects in the treatment of menorrhagia.

PMID- 17531614
TI  - The changing position of IUDs in reproductive health services in developing
      countries: opportunities and challenges.
AB  - The shared goals of contraceptive development and service delivery efforts are to
      help individuals and couples achieve their fertility intentions in a healthy,
      affordable and timely manner. Some would believe that now that contraceptive use
      has reached 60% in developing countries, there is little need for further
      investment in product research and development or family planning service
      delivery for developing countries. The expected growth (40%) in the demand for
      contraception by 2025 and the prevailing levels of unmet need for contraception
      (17%) in developing countries suggest that continued efforts to ensure that
      health systems and donors support family planning services are necessary. The IUD
      has the potential for enhancing women's health and the ability to both space and
      limit births at an affordable cost. Organizations involved in product research
      and development can join with service delivery partners to make new products more
      accessible to individuals in developing countries.

PMID- 17531615
TI  - Intrauterine devices - upper and lower genital tract infections.
AB  - The clinical diagnosis of a pelvic inflammatory disease (PID) is notoriously
      difficult. The incidence rate of PIDs among intrauterine device (IUD) users as
      reported from different studies depends heavily on the definition used and the
      means available for diagnosing PIDs. It varies by almost 10-fold from 1 per 100
      to 1 per 1000 woman-years in different publications. PID risk has been found to
      be 6-fold higher in the first month after IUD insertion than it is thereafter. It
      is not known if the overall PID risk in IUD users beyond the first month of IUD
      insertion is higher than that in nonusers; however, if it is higher, the
      additional risk is small. The PID risk in IUD users is modified by the number of
      sexual partners of the IUD user and that of her partner(s), community prevalence
      of STDs and age of the IUD user. Bacterial vaginosis appears not to be associated
      with IUD use. Overall, bacterial vaginosis is not associated with PIDs, but
      specific subgroups of patients with BV that may be difficult to identify
      clinically are at an increased risk for PIDs. Because of the long duration of use
      of current copper IUDs, replacement of the IUD is infrequent and insertion
      associated PIDs should consequently also be less frequent. IUD use has become
      safer with respect to PIDs through more effective screening and counseling
      procedures described in current guidelines for the initiation of IUD use. Current
      guidance must be followed to preserve the IUD as a safe contraceptive method.

PMID- 17531616
TI  - IUDs and colonization or infection with Actinomyces.
AB  - Pelvic actinomycosis is an extremely rare disease that can occur in women with a
      long duration of intrauterine device (IUD) use. This type of abscess is usually
      unsuspected and, thus, diagnosed and treated surgically; however, long-duration
      treatment with penicillin can be completely effective. While the occurrence of
      actinomycosis is well documented by case reports, it is not possible to quantify
      the risk during IUD use. Approximately 7% of women using an IUD may have a
      finding of Actinomyces-like organisms on a Pap test. The prognostic significance
      of this finding is minimal because of the lack of sensitivity and specificity and
      a low positive predictive value. In the absence of symptoms, women with
      Actinomyces-like organisms on a Pap test do not need antimicrobial treatment or
      IUD removal.

PMID- 17531617
TI  - Use of intrauterine devices and systems by HIV-infected women.
AB  - Human immunodeficiency virus (HIV)-infected women have unique contraceptive
      needs. HIV infection is now considered a chronic disease and contraceptive
      options have widened for HIV-infected women. However, there are safety concerns
      regarding the use of intrauterine devices and systems in HIV-infected women.
      Although studies are limited, intrauterine devices appear to be safe for use by
      most HIV-infected women. This is a review of the available data and international
      recommendations.

PMID- 17531618
TI  - Cochrane systematic reviews of IUD trials: lessons learned.
AB  - BACKGROUND: Intrauterine devices (IUDs) are the most widely used reversible
      contraceptives in the world today, and decisions about their use should reflect
      the best available evidence. STUDY DESIGN: We performed a computer search of the
      Cochrane Library for all IUD-related reviews. RESULTS: Eleven reviews related to
      IUDs have been registered in The Cochrane Library; 10 have been completed, and
      one is in progress. Topics include type of IUD, timing of insertion, clinical
      management, emergency contraception and use as gynecological treatment. The
      copper T380A is the most effective copper IUD; the levonorgestrel intrauterine
      system has efficacy comparable to that of IUDs with >250 mm(2) of copper. The
      frameless device may be comparable in efficacy to the copper T380A, although
      whether problems with the initial inserter are resolved is unclear. Immediate
      postpartum and postabortal insertion appears safe and effective, although trials
      comparing immediate to delayed insertions are scarce. Prophylactic antibiotics at
      the time of insertion appear unwarranted except in populations with a high
      prevalence of sexually transmitted diseases. Many nonsteroidal anti-inflammatory
      drugs reduce pain and bleeding associated with IUDs, although prophylactic use of
      ibuprofen does not improve continuation rates. The levonorgestrel system is
      superior to oral progestins in treating heavy uterine bleeding. This IUD compares
      favorably with endometrial ablation techniques and presents an alternative to
      hysterectomy for many women. DISCUSSION: Trials are needed to evaluate immediate
      vs. delayed insertion after delivery or abortion and to explore emerging
      therapeutic uses of the levonorgestrel system, such as treatment of endometrial
      hyperplasia.

PMID- 17531619
TI  - Neoplasia with use of intrauterine devices.
AB  - BACKGROUND: One of the mechanisms by which intrauterine devices (IUDs) prevent
      pregnancy is the creation of a sterile inflammatory response in the endometrium.
      Additionally, hormone-releasing IUDs or intrauterine systems (IUSs) release
      progestins or progesterone into the uterus. Both of these mechanisms may affect
      users' risk for neoplasia. STUDY DESIGN: We searched the PubMed database for
      studies on IUD use and risk for neoplasia conducted between 1960 and September
      2006 and published in all languages. We excluded case reports and case series.
      For the association between ever using an IUD and risk for endometrial cancer, we
      conducted a meta-analysis using a Bayesian random-effects model to account for
      between-study heterogeneity. RESULTS: We found no evidence of increased risk for
      neoplasia with IUD use. Nine case-control studies and one cohort study found
      reduced risks for endometrial cancer with having ever used an IUD (pooled
      adjusted odds ratio=0.6, 95% confidence interval=0.4-0.7). No trend in
      associations was observed with characteristics of IUD use, type of IUD and
      histologic type of cancer. Four case-control studies found no association between
      IUD use and risk for cervical cancer. One study found no increased incidence of
      breast cancer among levonorgestrel-releasing IUS users as compared with the
      general population in Finland. Finally, three studies found no association
      between IUD use and occurrence of hydatidiform moles or malignant sequelae.
      CONCLUSIONS: Use of an IUD does not appear to increase the risk for neoplasia.
      While nearly all studies found that IUD use was associated with a decreased risk
      for endometrial cancer, it remains unclear whether this association is causal.

PMID- 17531620
TI  - Utility and drawbacks of continuous use of a copper T IUD for 20 years.
AB  - This article examines interrelated questions concerning the extent of need for
      contraception in women 40 years and older and the degree to which that need can
      be served when use of collared T IUDs is initiated in women aged 25-35 years.
      Differentials in the impacts of intrauterine device (IUD) use on health issues in
      the second decade of contraception are also addressed. Although fertility of all
      women aged 40-44 years is below 100 per 1000 in all regions of the world today,
      the risk of pregnancy among married or cohabiting women who do not use
      contraception is estimated at 270-300 per 1000 or 27-30% per year. At ages 45-49
      years, the annual risk of pregnancy to women in union who do not use
      contraception lies at or above 10% per year. Data from three studies show that
      users of collared copper IUDs who continued using the same device beyond the
      completion of 10 years experienced no pregnancies through the end of 15 years. A
      small number of women continued with the same IUD through 20 years and still
      experienced no pregnancies. Use of collared copper T IUDs beyond 10 years was not
      associated with intensification of side effects nor with an increase in the
      relative frequency of those effects, with the exception of the experience of
      perimenopausal symptoms and problems. Neither increased bleeding nor increased
      severity of pelvic disease was manifest in the second decade of continuous use of
      the same IUD, as compared with the first decade of such use. Under our current
      understanding of the duration of IUD effectiveness, only a small percentage of
      women complete 10 years of use. Even with revised understanding of the duration
      of effectiveness of long-acting copper devices, average annual continuation rates
      must be quite high in order that 20% of women aged 25-35 years initiate a second
      decade of continuous IUD use. Those who do so would find considerable protection
      against pregnancy and reasonable economic benefits in continuing to use the same
      device.

PMID- 17531621
TI  - Contraindications to IUD and IUS use.
AB  - Contraindications to IUD or IUS use can be found on product labeling, in the
      guidelines of various specialty groups and in recommendations from peer-reviewed
      articles. Overly restrictive contraindications block access to this top-tier
      method for many women who would be candidates based on current scientific
      evidence. Assuming that a condition should be listed as a contraindication only
      if the risk of IUD/IUS use by a woman with that condition exceeds her risk with
      pregnancy, the list of contraindications is reduced to pregnancy, active uterine
      infection, malignancy in the uterus or cervix, an inability to place or retain
      the device, unexplained abnormal bleeding and adverse reaction to product
      ingredients.

PMID- 17531622
TI  - Copper intrauterine device use by nulliparous women: review of side effects.
AB  - BACKGROUND: Nulliparity was once a relative contraindication to using the copper
      IUD. However, new research and changes in product labeling have eased safety
      concerns. Side effects remain a major problem with copper IUD use in this
      population. METHODS: A review of published articles was undertaken to find
      information on expulsion rates and removals for bleeding and pain among
      nulliparous women using a copper IUD; approximately 500 articles and abstracts
      were found. RESULTS: In 15 studies comparing IUD performance in parous vs.
      nulliparous women, nulliparous women had higher rates of expulsion and removals
      due to bleeding and pain. Among 8 studies examining different types of copper
      IUDs in nulliparous women, some evidence suggests IUD size and shape play a role
      in performance. CONCLUSION: All existing copper IUDs are suitable for use by
      nulliparous women. However, more research is needed to determine whether
      expulsions and removals due to bleeding and pain can be reduced with improved
      copper devices.

PMID- 17531623
TI  - New frameless and framed intrauterine devices and systems - an overview.
AB  - There is a need for new, improved birth control methods which are easier to use,
      with less side effects and which avoid daily action, such as the pill. Perfect
      use requires consistent daily use or use at every act of intercourse. Long-acting
      methods eliminate the need for specific action at the time of coitus, or for
      daily action. Developing a new contraceptive is a major challenge. It is
      generally estimated that it takes 10-15 years to develop a new method and bring
      it to the market, at a cost of 200-300 million US dollars, and the industry is
      reluctant to take the risk of such long-term investment. However, both risk and
      investment can be reduced by taking small steps. Slight improvements of existing
      contraceptives could result in a giant step forward. The development of frameless
      intrauterine systems (IUS) is an attempt to improve the performance and
      acceptability of intrauterine contraception. Both the frameless GyneFix IUD and
      the frameless FibroPlant levonorgestrel (LNG)-IUS possess features which may
      solve the main problems encountered with conventional IUDs (e.g., expulsion,
      abnormal or excessive bleeding and pain). The performance of frameless devices,
      however, is dependent on correct anchoring of the device, which requires
      technical skill. Becoming a proficient GyneFix(R) or FibroPlant provider is
      easily acquired if the provider follows the procedural instruction strictly. For
      the less technically skilled provider, the Femilis LNG-IUS, using the new,
      simplified insertion technique, could be an excellent contraceptive option. It is
      usually not necessary to provide pain relief for insertion of an IUD/IUS,
      particularly in parous women. IUD providers should, however, realize that no
      woman likes to suffer from the insertion of an IUD. Severe discomfort may create
      a negative attitude towards the method. If the woman is anxious and fears pain
      (as most nulliparous women do), probably the most convenient, safe and effective
      method is to use local (intracervical) anesthesia using a dental syringe which
      can be applied with minimal risk in the office. In some women, the use of
      misoprostol 400 microg, 3 h prior to fitting of the IUD/IUS, may be useful to
      dilate the cervical canal. The popularity of the IUD could be much improved if
      attention is given to this aspect of IUD insertion.

PMID- 17531624
TI  - Endometrial effects of intrauterine levonorgestrel.
AB  - Local intrauterine delivery of levonorgestrel (LNG) results in extensive
      decidualization of endometrial stromal cells, atrophy of the glandular and
      surface epithelium and changes in vascular morphology (suppression of spiral
      artery formation and presence of large dilated vessels). With endometrial
      exposure to LNG, there is down-regulation of sex steroid receptors in all
      cellular components. As a consequence of endometrial sex steroid receptor down
      regulation, there is perturbation of progesterone-regulated locally acting
      mediators, and the integrity of blood vessel walls is disturbed. Thus,
      intrauterine LNG administration results in modulation of local mediators
      regulating endometrial function. To date, no single factor has been identified
      where the expression correlates closely with unscheduled breakthrough bleeding
      (BTB). BTB is a common side effect and reason for discontinuation of LNG-IUS use.
      Much remains to be determined about the mechanisms involved in suppression of
      menstruation, BTB episodes and the local endometrial environment with local LNG
      administration.

PMID- 17531625
TI  - Effects of levonorgestrel-releasing IUS and progesterone receptor modulator PRM
      CDB-2914 on uterine leiomyomas.
AB  - We have found that the use of levonorgestrel-releasing IUS results in a
      remarkable decrease in endometrial proliferation and a remarkable increase in
      apoptosis in the endometrium; therefore, it is effective for long-term management
      of menorrhagic women with uterine myomas because of the striking reduction in
      menorrhagia. This prompted us to characterize the effects of progesterone (P(4))
      and progesterone receptor modulator (PRM) CDB2914 on uterine myoma growth. In
      vitro studies with cultured uterine leiomyoma cells and normal myometrial cells
      revealed that P(4) stimulated the proliferative activity in leiomyoma cells, but
      not in normal myometrial cells. P(4) increased EGF expression, whereas E(2)
      augmented EGF-R expression in leiomyoma cells, indicating that P(4) and E(2) act
      in combination to stimulate leiomyoma cell growth. P(4) also increased Bcl-2
      expression and decreased TNF-alpha expression in those cells. Unlike the EGF
      expression, IGF-I expression in leiomyoma cells was inhibited by P(4). These
      results suggest that P(4) has dual actions on leiomyoma growth: one is to
      stimulate the growth through up-regulating EGF and Bcl-2 expression, and the
      other is to inhibit the growth through down-regulating IGF-I expression in the
      cells. By contrast, CDB2914 inhibited proliferation and stimulated apoptosis of
      leiomyoma cells without affecting normal myometrial cells. Furthermore, CDB2914
      inhibited vascular endothelial growth factor and adrenomedullin expression in
      leiomyoma cells, but not in normal myometrial cells. The cell type-specific
      action of CDB2914 on leiomyoma cells, without affecting the surrounding normal
      myometrial cells, is meaningful for understanding the usefulness of CDB2914 in
      the medical treatment of uterine myomas.

PMID- 17531627
TI  - Can endosonographers evaluate on-site cytologic adequacy? A comparison with
      cytotechnologists.
AB  - BACKGROUND: On-site determination of cytologic adequacy increases the accuracy of
      EUS-guided FNA (EUS-FNA); however, on-site cytotechnologists are not available to
      all endosonographers. We hypothesize that experienced endosonographers can
      accurately assess whether an on-site FNA specimen is adequate. OBJECTIVE: To
      determine the accuracy of on-site cytopathology interpretation of EUS-FNA
      specimens by comparing endosonographers with a cytotechnologist. DESIGN:
      Prospective double-blind controlled trial. SETTING: Academic medical center with
      a high-volume EUS practice. PATIENTS: Consecutive patients undergoing EUS-FNA of
      lymph nodes or pancreas tumors. MAIN OUTCOME MEASUREMENTS: Accuracy, sensitivity,
      and specificity of 3 endosonographers and 1 cytotechnologist for interpretation
      of cytologic specimen adequacy and diagnosis compared with a criterion standard
      of a board-certified cytopathologist. RESULTS: There were 59 lymph node, 49
      pancreas, and 9 liver specimens (117 total). For determination of adequacy, none
      of the endosonographers were statistically equivalent to the cytotechnologist
      (P=.004). For determination of suspicious/malignant versus benign specimens, all
      3 endosonographers were inferior (P<.001) to the cytotechnologist. LIMITATIONS:
      This study represents a small group of trained endosonographers in a high-volume
      practice and may not be applicable to other settings. The sample size does not
      allow an accurate evaluation of different biopsy sites (eg, pancreas vs lymph
      node). CONCLUSIONS: Even trained endosonographers have variable and, in some
      cases, inferior abilities to interpret on-site cytologic adequacy compared with
      cytotechnologists.

PMID- 17531628
TI  - The "super-endosonographer": can we and should we do it all?

PMID- 17531629
TI  - ERCP and prophylactic pancreatic stents: raising the bar, reducing the pain.

PMID- 17531630
TI  - EUS elastography of the pancreas: feasibility and pattern description of the
      normal pancreas, chronic pancreatitis, and focal pancreatic lesions.
AB  - BACKGROUND: Initial clinical applications have shown that US elastography might
      be able to distinguish tissues because of their specific consistency. OBJECTIVE:
      (1) To investigate the feasibility of EUS elastography of the pancreas and (2) to
      describe elastographic patterns of the normal pancreas and the pancreas affected
      by inflammatory or focal disease. DESIGN: Prospective single-center study.
      SETTING: Academic center of the University of Witten/Herdecke. PATIENTS: Twenty
      patients with normal pancreas, 20 patients with chronic pancreatitis, and 33
      patients with focal pancreatic lesion, histologically later proven in 32 of these
      33 cases. INTERVENTIONS: Commercially available US equipment was used. The
      elasticity of tissue was reconstructed in real time within a sample area and was
      translated into a color scale imaging relative tissue elasticity within this
      area. Representative loops of at least 20 seconds were recorded regarding each
      region of interest. RESULTS: Adequate elastographic recordings could be obtained
      in all 73 patients. Patients with hypoechoic and intermediately echogenic normal
      pancreas revealed a relatively homogeneous elastographic pattern. Thirty-one
      focal lesions, including 30 neoplasms and most of the chronically inflamed
      pancreata had a honeycomb pattern dominated by hard strands. This pattern showed
      analogies to the histologic structure of 10 resected tumors. Other patients with
      chronic pancreatitis and those with hyperechoic healthy pancreas had
      miscellaneous elastographic appearances. CONCLUSIONS: EUS elastography of the
      pancreas is feasible and produces plausible results. The examination of
      homogeneous tissue is impaired by the relative scale used. Chronic pancreatitis
      and hard tumors cannot be distinguished by elastography, probably because of
      their similar fibrous structure.

PMID- 17531631
TI  - EUS elastography: a step ahead?

PMID- 17531632
TI  - Efficacy of postprocedure administration of gabexate mesylate in the prevention
      of post-ERCP pancreatitis: a randomized, controlled, multicenter study.
AB  - BACKGROUND AND OBJECTIVE: Gabexate mesylate reduces the incidence of post-ERCP
      pancreatitis. Patient-related risk factors associated with pancreatitis can be
      identified before ERCP, but the procedure-related factors are recognized only at
      the end of the procedure. This study's aim was to evaluate whether gabexate
      mesylate administered after ERCP reduces the incidence of pancreatitis. DESIGN:
      Randomized, prospective, double-blind, multicenter trial. SETTING: Tertiary care
      centers. PATIENTS AND INTERVENTION: A total of 608 patients undergoing ERCP were
      treated with gabexate mesylate 500 mg within 1 hour before ERCP (group A, 203
      patients) or within 1 hour after ERCP (group B, 203), or with saline solution
      (group C, 202). MAIN OUTCOME MEASUREMENTS: The incidence and severity of
      pancreatitis and hyperamylasemia, as well as factors associated with the
      development of pancreatitis. RESULTS: The groups were similar for demographic
      characteristics, indications to ERCP, risk factors for pancreatitis, and
      therapeutic procedures. The incidence of pancreatitis was 3.9% in group A, 3.4%
      in group B, and 9.4% in group C (P<.01). Two patients (in groups A and C)
      developed necrotizing pancreatitis, and 1 died. Hyperamylasemia occurred in 23.6%
      in groups A and B, and in 24.7% in group C. Levels of amylase, the incidence of
      abdominal pain, and other complications occurred similarly. Female sex (odds
      ratios [OR] 2.7, 95% CI 1.2-5.9) and difficult cannulation (OR 5.6, 95% CI 2.6
      12.3) were independently associated with pancreatitis. CONCLUSIONS: The
      administration of gabexate mesylate after ERCP protects against the development
      of pancreatitis similarly to the preprocedure administration. Factors associated
      with pancreatitis were mainly recognized after ERCP. We suggest administering
      gabexate mesylate after ERCP only in those patients recognized to be at risk of
      developing pancreatitis.

PMID- 17531633
TI  - The beginning of a new paradigm in colonoscopy?

PMID- 17531634
TI  - Visible dysplasia: what you see is most of what you get.

PMID- 17531635
TI  - Percutaneous endoscopic colostomy of the left side of the colon.
AB  - BACKGROUND: Percutaneous endoscopic colostomy (PEC) on the left side of the colon
      is a minimally invasive endoscopic technique, increasingly used to treat lower-GI
      conditions. OBJECTIVE: To evaluate the efficacy and safety of a PEC tube
      insertion at a single unit. DESIGN: Retrospective data collection. SETTING:
      District general and teaching hospital in the United Kingdom. PATIENTS: Data
      collected from patients with lower-GI disorders who had a PEC tube inserted.
      INTERVENTIONS: Data collection. MAIN OUTCOME MEASUREMENTS: Incidence of
      complications and patient outcome. RESULTS: Between 2001 and 2005, 31 patients
      presented for a PEC. Insertion was possible in 27 patients. Indications included
      functional constipation (n=8), recurrent sigmoid volvulus (n=8), colonic pseudo
      obstruction (n=5), and neurologic constipation (n=6). In 22 patients (81%),
      symptoms were markedly improved after insertion. Sigmoid volvulus did not recur
      with a PEC tube in place. The mean (standard error of the mean) duration with
      tubes in situ was 9.5+/-1.6 months. Only 2 patients still had a PEC tube in situ.
      A total of 77% of patients had episodes of infection. Infective episodes led to
      tube removal in 44% of the total group. Other complications included buried
      internal bolster, fecal leakage, and pain. Mortality was high (26%), with 7
      deaths: 5 from unrelated causes and 2 deaths from fecal peritonitis. LIMITATIONS:
      This was a retrospective study. A prospective study in our unit is unlikely
      because of these results. CONCLUSIONS: Symptoms were effectively controlled by a
      PEC tube insertion, and recurrent sigmoid volvulus was prevented. Recurrent
      complications caused significant morbidity. Infection necessitated tube removal
      in the majority of patients. Fatal fecal peritonitis occurred in 2 patients.
      Indiscriminate use of a PEC in the left side of the colon is not recommended. A
      PEC should only be considered in carefully selected cases.

PMID- 17531636
TI  - Colorectal neoplasm in asymptomatic Asians: a prospective multinational
      multicenter colonoscopy survey.
AB  - BACKGROUND: Colorectal neoplasm is rapidly increasing in Asia, but a guideline
      for screening is not available. OBJECTIVE: To evaluate the characteristics of
      colorectal neoplasm in asymptomatic Asian subjects. DESIGN: Prospective cohort
      study. SETTING: Multinational multicenters, including both primary and referral
      centers in Asia. PATIENTS: A total of 860 consecutive asymptomatic adults
      undergoing screening colonoscopy in 11 Asian cities from July 2004 to December
      2004. Patients under 16 years old; those patients with a colorectal resection
      history, colonoscopies, or barium enema within 5 years; symptoms suggestive of
      colorectal diseases; and those who had undergone surveillance colonoscopy were
      excluded. MAIN OUTCOME MEASUREMENTS: The incidence and distribution of colorectal
      neoplasm and advanced neoplasm. RESULTS: The mean age (+/-SD) was 54.4+/-11.6
      years; 471 were men (54.8%). The prevalence of colorectal neoplasm and advanced
      neoplasm was 18.5% and 4.5%, respectively. Male sex, advancing age, and a family
      history of colorectal cancer were risk factors for advanced neoplasm. Of the 168
      patients with colorectal neoplasm, 76 had distal neoplasm only (45.2%), 66 had
      proximal neoplasm only (39.3%), and 26 had both proximal and distal neoplasms
      (15.5%). Although the presence of distal advanced neoplasm was a significant risk
      factor for proximal advanced neoplasm, 14 of the 758 subjects without distal
      neoplasm had proximal advanced neoplasm (1.8%). LIMITATIONS: The small number of
      enrolled subjects, especially from certain ethnic groups. CONCLUSIONS: The
      overall prevalence of advanced colorectal neoplasm in asymptomatic Asians is
      comparable with the West. Male sex, advancing age, and a family history of
      colorectal cancer were associated with a higher risk of advanced neoplasm.

PMID- 17531637
TI  - Transgastric cholecystectomy: transgastric accessibility to the gallbladder
      improved with the SEMF method and a novel multibending therapeutic endoscope.
AB  - BACKGROUND: Transgastric cholecystectomy is thought to technically and
      anatomically challenge a single entry flexible endoscopic approach. OBJECTIVES:
      To examine the feasibility of a transgastric-only cholecystectomy, endoscope
      performance in an upper-abdominal operation, and the usefulness of an offset
      gastrotomy. STUDY DESIGN: Animal survival study. SETTING: Animal research
      laboratory. PATIENTS: Six domestic pigs. MAIN OUTCOME MEASUREMENTS: Transgastric
      access to the gallbladder and technical feasibility of unassisted transgastric
      cholecystectomy. INTERVENTIONS: A cephalad submucosal tunnel was created in the
      anterior gastric wall with a high-pressure CO2 injection. An EMR-cap myotomy was
      performed distally within the submucosal space and created an offset gastrotomy.
      An endoscope was inserted into the peritoneal cavity through the myotomy. Access
      to the gallbladder was compared by using a multibending therapeutic endoscope (R
      scope), with a standard double-channel endoscope. A cholecystectomy was performed
      by using both types of endoscopes. The myotomy site was sealed with the overlying
      mucosal flap. The mucosal entry point was closed with clips or tissue anchors.
      RESULTS: A standard double-channel endoscope could access the gallbladder in 2 of
      4 attempts. A multibending endoscope accessed the gallbladder in all 4 attempts,
      including 2 pigs in which the standard scope failed to access the gallbladder. In
      4 pigs, a cholecystectomy was completed. Two pigs died during surgery, with air
      embolization observed in 1. Two pigs survived a planned 1-week survival period.
      CONCLUSIONS: Transgastric cholecystectomy is technically feasible. Transgastric
      access to the gallbladder may be improved by using submucosal endoscopy with an
      offset exit gastrotomy by means of the mucosal flap safety-valve technique and a
      multibending gastroscope.

PMID- 17531638
TI  - Developing an academic EUS program: the University of Alabama at Birmingham
      experience.

PMID- 17531639
TI  - Endoscopic colorectal cancer screening in women: can we do better?

PMID- 17531640
TI  - An animal training model for endoscopic treatment of Zenker's diverticulum.
AB  - BACKGROUND: Zenker's diverticulum (ZD) is an uncommon disease, which is typically
      treated surgically. The alternative to surgery is a diverticulotomy, performed
      endoscopically. Given the rarity of this condition, it is not possible to obtain
      training. There has been no animal model identified that resembles the disease in
      human beings. OBJECTIVE: To present an animal model of ZD that resembles the
      disease in human beings. DESIGN: We prospectively characterized the endoscopy,
      the radiography, and the histologic anatomy of the pharyngeal diverticulum in the
      pig. SETTINGS: Domestic pigs scheduled for euthanasia underwent radiography and
      endoscopy and, after euthanasia, neck dissection of the pharyngeal diverticulum.
      INTERVENTIONS AND METHODS: Thirteen consecutive animals were studied. Pictures
      were taken for the endoscopic view, as well as radiographies during barium
      swallow in 1 pig. The neck region was dissected, and the pharynx and the upper
      esophagus were extracted. The size of the diverticulum was measured, and the
      block was fixed in formalin. Fixed specimens were cut in the transverse and
      coronal axis, and pictures were taken. The septum between the diverticulum and
      the esophagus was reviewed microscopically. RESULTS: The pharyngeal diverticulum
      measured an average of 2.7 cm (1.3-5 cm), depending on the size of the pig. From
      an endoscopic and radiologic perspective, the pig pharyngeal diverticulum is
      identical to a ZD. The septum contains muscle as well as fibrous tissue and fat.
      These anatomical characteristics closely resemble the anatomy in human beings.
      CONCLUSIONS: We believe that we established an animal training model for the
      endoscopic treatment of ZD.

PMID- 17531641
TI  - Endoscopic treatment of Zenker's diverticulum.

PMID- 17531642
TI  - Development of a novel ERCP mechanical simulator.
AB  - BACKGROUND: There is a paucity of objective methods for evaluating trainee
      performance and comparing ERCP accessories. OBJECTIVE: Use of a mechanical ERCP
      simulator to evaluate trainee performance and to compare ERCP accessories via
      procedure time. DESIGN: Pilot study using a mechanical simulator. SETTING: Hands
      on ERCP practice workshops. SUBJECTS: Endoscopists at various levels of ERCP
      experience. METHOD: Validation studies are described to show that the simulator
      permits participants with varying ERCP experience to demonstrate their skill
      levels and offers novel training applications in ERCP courses. The time required
      for completing a simulated stent placement procedure, simulated fluoroscopy time,
      and participant expectations were recorded in different settings. Participants'
      expectations were compared before and after training to determine whether the
      simulator was a credible adjunct to ERCP training. RESULTS: Significantly shorter
      procedure times were recorded for the same accessories used by participants with
      more ERCP experience than those with less experience and for the same group of
      participants when using accessories with 1 design compared with another. The mean
      total credibility score showed a significant increase after simulator practice.
      LIMITATIONS: In vitro practice by using a mechanical simulator; results may not
      translate directly to the clinical setting. How the objective procedure times
      measured during practice can complement assessment of trainee competence or
      define usefulness of different accessories is unknown but deserves to be explored
      in future studies. CONCLUSIONS: The procedure times can categorize participants
      according to their ERCP experience and separate accessories according to their
      ease of use. An increase in credibility score validates participants' endorsement
      of such practice as a credible adjunct to ERCP training.

PMID- 17531643
TI  - A novel biodegradable biliary stent in the endoscopic treatment of cystic-duct
      leakage after cholecystectomy.
AB  - BACKGROUND: A bile leak is a common complication after a cholecystectomy.
      OBJECTIVE: The use of a novel, self-expanding, radiopaque polylactide-barium
      sulphate biodegradable stent and a polyethylene stent was investigated in 12 pigs
      with cystic-duct leakage. DESIGN: Prospective animal study. SETTING: After
      cholecystectomy, the cystic duct was left without ligation, and then the foramen
      of Winslow was drained extra-abdominally. During the duodenoscopy, a
      biodegradable or a polyethylene biliary stent was inserted into the bile duct.
      MAIN OUTCOME MEASUREMENTS: The bile-drain output was measured daily, and when it
      was below 20 mL/d, the drain was removed. The animals were followed by repeated
      abdominal radiographs and serum determinations until they were euthanized at 6
      months, when histologic evaluation of the bile duct and surrounding tissues was
      performed. RESULTS: In the biodegradable stent group, the total external output
      of bile was significantly smaller (median [range], 165 mL [100-1740 mL] vs 710 mL
      [355-1020 mL]; P<.01) and the drains could be removed earlier (5 days [4-5 days]
      vs 7 days [6-7 days] after surgery; P<.05) compared with the plastic stent group.
      In the abdominal radiograph, a biodegradable or polyethylene stent was seen to be
      in place in all animals at 3 months and in 0 of 6 (biodegradable biliary stent
      group) and 1 of 5 (polyethylene biliary stent group) animals at 6 months. One
      polyethylene stent was found to be clotted at the necropsy at 6 months. The rest
      of the stents had disappeared by 6 months, and there was no significant
      difference in the bile-duct inner diameter or the histology between the groups.
      CONCLUSIONS: This novel biodegradable stent is applicable, safe, and effective in
      the endoscopic treatment of postcholecystectomy cystic-duct leakage. In addition,
      the subsequent removal of the stent can be avoided. These encouraging
      experimental results warrant further clinical trials.

PMID- 17531644
TI  - Endoscopic treatment of bile leaks: current standards and recent innovations.

PMID- 17531645
TI  - A case of a giant colonic hemangioma presenting as iron deficiency anemia.

PMID- 17531646
TI  - Endoscopic management of traumatic bile leaks.
AB  - BACKGROUND: Traumatic bile leaks often result in prolonged morbidity and an
      increased length of hospital stay that requires multimodality management. Data on
      endoscopic management of traumatic bile leaks are scarce. OBJECTIVE: To evaluate
      the efficacy of endotherapy in the management of traumatic bile leaks. DESIGN:
      Retrospective evaluation of prospectively collected data. SETTING: Tertiary
      academic referral center. PATIENTS: Consecutive patients referred for ERCP after
      traumatic abdominal injury for the management of bile leaks. INTERVENTIONS:
      Biliary stent placement at ERCP. MAIN OUTCOME MEASURES: Resolution of a bile leak
      on follow-up ERCP. RESULTS: Ten patients underwent ERCP for the management of a
      traumatic bile leak over a 3-year period. The etiology included a penetrating
      injury from a gunshot wound in 5 patients, blunt injuries from a motor vehicle
      accident in 4 patients, and injury secondary to a fall in 1 patient. Liver
      injuries were grade II in 1 patient, grade IV in 7 patients, and grade V in 2
      patients. A bile leak was treated by biliary stent placement in all patients, and
      the outcome was successful in 9 of 10 cases (90%). The mean duration of follow-up
      was 337 days (range, 101-821 days). Nine of 10 patients underwent surgery to
      control bleeding or other associated injuries. There were no ERCP-related
      complications. LIMITATIONS: Small number of patients. CONCLUSIONS: Consideration
      should be given to incorporate ERCP as first-line therapy in management of
      traumatic bile leaks, because endobiliary stent placement provides a successful
      outcome in a majority of cases, irrespective of the severity of injury.

PMID- 17531647
TI  - Menetrier's disease associated with herpes infection: response to treatment with
      acyclovir.

PMID- 17531648
TI  - EUS staging of upper GI malignancies: results of a prospective randomized trial.

PMID- 17531649
TI  - Successful recovery of esophageal patency in 2 patients with complete obstruction
      by using combined antegrade retrograde dilation procedure, needle knife, and EUS
      needle.

PMID- 17531650
TI  - Use of topical pharyngeal anaesthesia before gastroscopy by British
      gastroenterologists.

PMID- 17531652
TI  - Risks of oral sodium phosphate for precolonoscopy bowel preparation in children.

PMID- 17531655
TI  - Plaque neovascularization and antiangiogenic therapy for atherosclerosis.
AB  - The concept that neovascularization of the vessel wall may play a fundamental
      role in the pathophysiology of atherosclerosis was proposed more than a century
      ago. In recent years, supportive experimental evidence for this hypothesis (such
      as the finding that neointimal microvessels may increase delivery of cellular and
      soluble lesion components to the vessel wall) has been underscored by clinical
      studies associating plaque angiogenesis with more rapidly progressive high-grade
      disease. Attention has also focused on a possible role for microvessel-derived
      intraplaque hemorrhage in the development of acute lesion instability. The
      interest of clinicians in this phenomenon has been spurred by the potential to
      target vessel wall neovascularization with angiogenesis inhibitors, a therapeutic
      approach that has been associated with impressive reductions in plaque
      progression in animal models of vascular disease. The rationale for pursuing an
      "antiangiogenic" strategy in the treatment of patients with vascular disease, and
      a framework for further preclinical evaluation of such therapy, is presented
      here.

PMID- 17531656
TI  - Total cholesterol content of erythrocyte membranes is increased in patients with
      acute coronary syndrome: a new marker of clinical instability?
AB  - OBJECTIVES: We hypothesized that cholesterol content is increased in the
      circulating erythrocytes of patients with acute coronary syndrome (ACS) and may
      be a marker of clinical instability. We therefore sought to investigate whether
      cholesterol content differs in erythrocyte membranes of patients presenting with
      ACS compared to patients with chronic stable angina (CSA). BACKGROUND: Plaque
      rupture in ACS depends at least partly on the volume of the necrotic lipid core.
      Histopathologic studies have suggested that cholesterol transported by
      erythrocytes and deposited into the necrotic core of atheromatous plaques
      contributes to lipid core growth. METHODS: Consecutive angina patients were
      prospectively assessed; 120 had CSA (83 men, age 64 +/- 11 years) and 92 ACS (67
      men, 66 +/- 11 years). Total cholesterol content in erythrocyte membranes (CEM)
      was measured using an enzymatic assay, and protein content was assessed by the
      Bradford method. RESULTS: The CEM (median and interquartile range) was higher (p
      < 0.001) in ACS patients (184 microg/mg; range 130.4 to 260.4 microg/mg) compared
      with CSA patients (81.1 microg/mg; range 53.9 to 109.1 microg/mg) (analysis of
      covariance). Total plasma cholesterol concentrations did not correlate with CEM
      levels (r = -0.046, p = 0.628). CONCLUSIONS: This study shows, for the first
      time, that CEM is significantly higher in patients with ACS compared with CSA
      patients. These findings suggest a potential role of CEM as a marker of
      atheromatous plaque growth and vulnerability. Large ad hoc studies are required
      to establish the clinical importance and pathogenic significance of CEM
      measurement.

PMID- 17531657
TI  - Total erythrocyte membrane cholesterol: an innocent new marker or an active
      player in acute coronary syndromes?

PMID- 17531658
TI  - Elimination of neoangiogenesis for plaque stabilization: is there a role for
      local drug therapy?
AB  - Emerging data suggest that intraplaque hemorrhage is critical in promoting
      atherosclerotic lesion instability. Because red blood cell membranes are a rich
      source of free cholesterol and accumulated red blood cells within plaques promote
      inflammation, intraplaque hemorrhage is associated with expansion of the necrotic
      core. Plaque hemorrhage results from the development of immature neointimal vasa
      vasorum. Therefore, it is proposed that molecular therapies designed to eliminate
      pathologic neovascularization within developing lesions will interrupt the
      process of hemorrhage and decrease the rate of necrotic core expansion. The
      elimination of intraplaque neovascularization would involve targeting of pre
      existing and new vessel development. The concept of vascular regression has met
      some success in other neovascular-dependent diseases, including macular
      degeneration and malignancies. The efficacy of this novel approach is dependent
      on gaining critical knowledge of the environment required to support development
      and maturation of the vasa vasorum within varying plaque types. A multitargeted
      approach involving selective local antiangiogenic agents should contribute to
      prevention of plaque progression and its clinical consequences.

PMID- 17531659
TI  - Atherosclerosis in the back yard.
AB  - The phenomenon of neovascularization in atherosclerosis has been widely
      recognized through "the eyes of novel imaging techniques" in recent years.
      Oxidative stress, inflammation, and hypoxia have been implied as the underlying
      mechanisms. The pathophysiologic consequences and therapeutic implications of
      this neovascularization process for atherosclerosis have, however, remained
      challenging and controversial. In the current focus issue of the Journal, 4
      articles and this commentary are devoted to this topic.

PMID- 17531660
TI  - Percutaneous coronary intervention of functionally nonsignificant stenosis: 5
      year follow-up of the DEFER Study.
AB  - OBJECTIVES: The purpose of this study was to investigate the appropriateness of
      stenting a functionally nonsignificant stenosis. BACKGROUND: Percutaneous
      coronary intervention (PCI) of an intermediate stenosis without evidence of
      ischemia is often performed, but its benefit is unproven. Coronary pressure
      derived fractional flow reserve (FFR) is an invasive index used to identify a
      stenosis responsible for reversible ischemia. METHODS: In 325 patients scheduled
      for PCI of an intermediate stenosis, FFR was measured just before the planned
      intervention. If FFR was >or =0.75, patients were randomly assigned to deferral
      (Defer group; n = 91) or performance (Perform group; n = 90) of PCI. If FFR was
      <0.75, PCI was performed as planned (Reference group; n = 144). Clinical follow
      up was 5 years. RESULTS: There were no differences in baseline clinical
      characteristics between the 3 groups. Complete follow-up was obtained in 98% of
      the patients. Event-free survival was not different between the Defer and Perform
      groups (80% and 73%, respectively; p = 0.52), but was significantly worse in the
      Reference group (63%; p = 0.03). The composite rate of cardiac death and acute
      myocardial infarction in the Defer, Perform, and Reference groups was 3.3%, 7.9%,
      and 15.7%, respectively (p = 0.21 for Defer vs. Perform group; p = 0.003 for the
      Reference vs. both other groups). The percentage of patients free from chest pain
      at follow-up was not different between the Defer and Perform groups. CONCLUSIONS:
      Five-year outcome after deferral of PCI of an intermediate coronary stenosis
      based on FFR >/=0.75 is excellent. The risk of cardiac death or myocardial
      infarction related to this stenosis is <1% per year and not decreased by
      stenting.

PMID- 17531661
TI  - Insulin resistance, the metabolic syndrome, and risk of incident cardiovascular
      disease: a population-based study.
AB  - OBJECTIVES: The goal was to clarify if insulin resistance (IR) would predict
      cardiovascular disease (CVD) independent of the metabolic syndrome (MetSyn).
      BACKGROUND: Although the cause of MetSyn is not well defined, IR has been
      proposed to be an important cause. Only a small number of population-based
      studies have sought to clarify if IR predicts CVD independent of MetSyn. METHODS:
      This was a prospective Danish population-based study of 2,493 men and women, age
      41 to 72 years, without major CVD at baseline. We defined MetSyn according to
      both the International Diabetes Foundation (IDF) and the National Cholesterol
      Education Program (NCEP) criteria, and we quantified IR by the homeostasis model
      assessment (HOMA-IR). Prevalence of MetSyn was 21% according to IDF criteria and
      16% according to NCEP criteria. Accordingly, we defined IDF-HOMA-IR as belonging
      to the highest 21% of the HOMA-IR distribution, and NCEP-HOMA-IR as belonging to
      the highest 16% of the HOMA-IR distribution. RESULTS: Over a median follow-up of
      9.4 years, the incidence of CV end points (CV death, nonfatal ischemic heart
      disease, and nonfatal stroke) amounted to 233 cases. In proportional hazard
      models, adjusting for age, gender, smoking, and low-density lipoprotein
      cholesterol, and with IDF-HOMA-IR and IDF-MetSyn included in the same model, the
      relative risk of an end point was 1.67 (95% confidence interval [CI] 1.22 to
      2.29) for IDF-HOMA-IR and 1.16 (95% CI 0.84 to 1.60) for IDF-MetSyn. The
      corresponding figures for NCEP-HOMA-IR and NCEP-MetSyn included in the same model
      were 1.49 (95% CI 1.07 to 2.07) and 1.56 (95% CI 1.12 to 2.17). CONCLUSIONS: In
      this Danish study, both HOMA-IR and NCEP-MetSyn were independent predictors of
      incident CVD.

PMID- 17531662
TI  - Therapy with cardiac contractility modulation electrical signals improves left
      ventricular function and remodeling in dogs with chronic heart failure.
AB  - OBJECTIVES: This study examined the effects of long-term delivery of cardiac
      contractility modulation (CCM) electric signals on left ventricular (LV) function
      and global, cellular, and molecular remodeling in dogs with chronic heart failure
      (HF). BACKGROUND: Acute studies in dogs with experimentally induced HF showed
      that CCM signals applied to the failing myocardium during the absolute refractory
      period improved LV function without increasing myocardial oxygen consumption.
      METHODS: In one study, dogs with intracoronary microembolization-induced HF were
      randomized to 3 months of active CCM monotherapy or to a sham-operated control
      group. In another study, 19 HF dogs were randomized to 3 months chronic
      monotherapy with extended release metoprolol succinate (MET-ER), MET-ER with CCM,
      or no therapy at all (control group). RESULTS: In CCM-only treated dogs, LV
      ejection fraction (EF) increased (27 +/- 1% vs. 33 +/- 1%, p < 0.0001) compared
      with a decrease in sham-operated control animals (27 +/- 1% vs. 23 +/- 1%, p <
      0.001). The increase in EF seen with CCM-treated dogs was accompanied by reduced
      LV volumes, improved myocardial structure, reversal of the maladaptive fetal gene
      program, and an improvement in sarcoplasmic reticulum calcium cycling proteins.
      Dogs treated with a combination of MET-ER and CCM showed a greater increase in LV
      EF and a greater reversal of LV global, structural, and biochemical remodeling
      compared with dogs treated with MET-ER alone. CONCLUSIONS: In dogs with HF, long
      term CCM therapy improves LV systolic function. The improvements are additive to
      those seen with beta-blockers. These findings are further strengthened by the
      concomitant benefits of CCM therapy on LV global, cellular, and biochemical
      remodeling.

PMID- 17531663
TI  - C-reactive protein and the prediction of cardiovascular events among those at
      intermediate risk: moving an inflammatory hypothesis toward consensus.
AB  - Over 20 large-scale prospective studies show that the inflammatory biomarker high
      sensitivity C-reactive protein (hsCRP) is an independent predictor of future
      cardiovascular events that additionally predicts risk of incident hypertension
      and diabetes. In many studies, the relative impact of hsCRP is at least as large
      as that individually of low-density lipoprotein cholesterol, high-density
      lipoprotein cholesterol, blood pressure, or smoking, and knowledge of hsCRP
      correctly reclassifies a substantial proportion of "intermediate-risk"
      individuals into clinically relevant higher- or lower-risk categories. Other
      studies show the relative benefit of statins to be greater among those with
      increased hsCRP and that achieved hsCRP levels after statin therapy predict
      recurrent event rates as much as achieved levels of low-density lipoprotein
      cholesterol. Nonetheless, it remains controversial whether the time has come to
      modify traditional algorithms used for global risk detection. As described here,
      6 areas of controversy regarding hsCRP are resolvable with a consensus position
      that focuses in primary prevention on selective use among individuals with 5% to
      20% 10-year risk as estimated by Adult Treatment Panel III, and focuses in
      secondary prevention on high-risk patients being treated with statin therapy.
      Forthcoming trial data could expand or contract this "screen selectively" policy,
      and investigators should be open to the possibility that second-generation
      inflammatory biomarkers may be developed that supplant hsCRP altogether. In the
      meantime, however, this consensus position on hsCRP should be one to which both
      advocates and critics of the inflammatory hypothesis of atherosclerosis can
      adhere because it is one that can immediately improve patient care.

PMID- 17531664
TI  - High-sensitivity C-reactive protein in every chart? The use of biomarkers in
      individual patients.
AB  - The use of high-sensitivity C-reactive protein (hsCRP) for risk stratification
      for cardiovascular disease is supported by epidemiologic evidence but remains
      controversial. The metabolic milieu in which hsCRP is likely to be elevated,
      namely abdominal obesity and insulin resistance, provides a framework for the
      understanding of the role of hsCRP as well its limitations. This commentary
      provides a critical assessment of the data in support of the use of hsCRP in
      clinical practice.

PMID- 17531665
TI  - Carvedilol for anthracycline cardiomyopathy prevention.

PMID- 17531667
TI  - Ectasia.

PMID- 17531668
TI  - Phacovitrectomy: expanding indications.

PMID- 17531670
TI  - Safety of posterior-assisted levitation.

PMID- 17531671
TI  - Intraocular lens implantation in cases with anterior capsule tears extending to
      the posterior capsule.

PMID- 17531673
TI  - Seven year follow-up of combined cataract extraction and viscocanalostomy.

PMID- 17531674
TI  - Corneal ectasia after photorefractive keratectomy.

PMID- 17531676
TI  - Prophylaxis for IFIS.

PMID- 17531678
TI  - Consultation section: cataract surgical problem.

PMID- 17531684
TI  - Sutureless single-port transconjunctival pars plana limited vitrectomy combined
      with phacoemulsification for management of phacomorphic glaucoma.
AB  - We describe a technique that uses a small-gauge, single-port, sutureless
      transconjunctival limited pars plana vitrectomy to facilitate phacoemulsification
      in eyes with a shallow anterior chamber and high intraocular pressure
      (phacomorphic glaucoma). These eyes have positive vitreous pressure, and anterior
      chamber formation with an ophthalmic viscosurgical device may not be possible.
      Surgery is difficult and prone to various intraoperative complications.

PMID- 17531685
TI  - Ab externo direct suture technique for dislocated intraocular lens.
AB  - We describe a scleral fixation technique that uses an ab externo direct suture
      through the eyelet of a dislocated intraocular lens (IOL). This modified
      technique may provide an easy and effective way to reposition a dislocated
      posterior chamber IOL.

PMID- 17531686
TI  - Automated vitrector-assisted optical iridectomy: customized iridectomy.
AB  - An automated vitrector was used to create an optical iridectomy in 15 eyes of 15
      patients with leucomatous corneal opacities. The optical iridectomy was performed
      successfully through a standard 1.2 mm incision in all eyes. No intraoperative
      complications were observed, and there was no case of iatrogenic cataract
      formation. The median best corrected visual acuity improved from 1/60 (range
      light perception to 6/60) preoperatively to 6/24 (range 6/60 to 6/12) at the last
      follow-up (mean 28 days). An automated vitrector can be successfully used to
      create an optical iridectomy in eyes with leucomatous corneal opacities. This
      technique was safe and could be performed through a small surgical incision.

PMID- 17531687
TI  - Surgical technique for suture fixation of a single-piece hydrophilic acrylic
      intraocular lens in the absence of capsule support.
AB  - We present a new intraocular lens (IOL) fixation technique that reduces the
      presence of intraocular knots and eliminates the need for scleral flaps while
      attaining excellent central positioning of the IOL. It also provides rapid visual
      rehabilitation from the insertion of a foldable IOL through a small corneal
      incision. This single-loop suture technique is an easy, convenient, and practical
      procedure, with minimum complications in the treatment of aphakia and the
      management of cataract surgery in eyes without capsular support.

PMID- 17531688
TI  - Sequential Intacs and Verisyse phakic intraocular lens for refractive improvement
      in keratoconic eyes.
AB  - PURPOSE: To evaluate the safety, efficacy, and stability of sequential Intacs
      (Addition Technology, Inc.) insertion and Verisyse phakic intraocular lens (pIOL)
      (AMO) implantation in selected cases of keratoconus. SETTING: Magrabi Eye
      Hospital, Cairo, Egypt. METHODS: Prospective data were collected from 8 eyes of 6
      keratoconus patients with contact lens intolerance, clear corneas, a maximum K
      value less than 60.0 diopters (D), and minimum corneal thickness greater than 400
      mum. Two 0.45 mm Intacs were inserted through a 1.8 mm radial incision created at
      70% of the corneal depth opposite the cone apex. The 2 rings were pushed to meet
      and embrace the cone apex. Refraction 6 months after Intacs insertion showed
      residual myopia greater than 6.0 D and residual astigmatism not more than 2.0 D.
      Thus, a phakic Verisyse IOL was implanted horizontally in the anterior chamber
      through a 6.5 mm superior clear corneal incision, which was closed with 3, 10-0
      nylon sutures after a peripheral iridectomy was created. The uncorrected visual
      acuity (UCVA), best corrected visual acuity (BCVA), refraction, and topographic
      profiles were taken 1 week and 1, 3, 6, 9, 12, 18, and 24 months after the second
      surgery. RESULTS: All eyes achieved UCVA of 20/40 or better. The final spherical
      error ranged from -1.75 to +1.00 D and the cylindrical error, from 1.25 to 2.50
      D. No eye lost lines of preoperative BCVA. These results were relatively stable
      throughout the follow-up period. CONCLUSIONS: Sequential Intacs and a Verisyse
      pIOL implantation was safe, stable, and effective in selected cases of
      keratoconus. It is a reversible surgery that is less invasive than penetrating
      keratoplasty (PKP). It can avoid or postpone the need for PKP, although it is not
      an alternative.

PMID- 17531689
TI  - One-year results of photorefractive keratectomy and laser in situ keratomileusis
      for myopia using a 213 nm wavelength solid-state laser.
AB  - PURPOSE: To study the long-term results of photorefractive keratectomy (PRK) and
      laser in situ keratomileusis (LASIK) in low to moderate myopic corrections using
      the Pulzar Z1 system (CustomVis), a 213 nm wavelength solid-state laser. SETTING:
      University refractive surgery center. METHODS: This prospective noncomparative
      case series comprised 20 patients (40 eyes) who had refractive surgery using the
      Pulzar Z1 laser system. Manifest refraction, uncorrected visual acuity, best
      spectacle-corrected visual acuity (BSCVA), safety, predictability, stability, and
      confocal microscopy images were evaluated. RESULTS: Ten patients (20 eyes) had
      PRK and 10 patients (20 eyes) had LASIK. The mean follow-up was 13.9 months +/-
      1.1 (SD) (range 12 to 17 months) and 14.6 +/- 1.2 months (range 12 to 18 months)
      in the PRK group and LASIK group, respectively. No eye lost a line of Snellen
      BSCVA during the follow-up period; 2 eyes (10%) gained 2 Snellen lines. There was
      a statistically significant decrease in spherical equivalent manifest refraction
      postoperatively in both groups (P<.05). Refractive stability was obtained during
      the first postoperative month and remained stable during the follow-up period,
      with no significant changes between any interval in both groups (P>.05). At the
      last follow-up, 95% of all eyes were within +/-1.00 diopter of emmetropia. No
      late postoperative complications were observed. CONCLUSION: Refractive surgery
      using the Pulzar Z1 213 nm wavelength solid-state laser was a safe, effective
      procedure in the treatment of low to moderate myopia.

PMID- 17531690
TI  - Prophylaxis of postoperative endophthalmitis following cataract surgery: results
      of the ESCRS multicenter study and identification of risk factors.
AB  - PURPOSE: To identify risk factors and describe the effects of antibiotic
      prophylaxis on the incidence of postoperative endophthalmitis after cataract
      surgery based on analysis of the findings of the European Society of Cataract &
      Refractive Surgeons (ESCRS) multicenter study. SETTING: Twenty-four ophthalmology
      units in Austria, Belgium, Germany, Italy, Poland, Portugal, Spain, Turkey, and
      the United Kingdom. METHODS: A prospective randomized partially masked
      multicenter cataract surgery study recruited 16 603 patients. The study was based
      on a 2 x 2 factorial design, with intracameral cefuroxime and topical
      perioperative levofloxacin factors resulting in 4 treatment groups. The
      comparison of case and non-case data was performed using multivariable logistic
      regression analyses. Odds ratios (ORs) associated with treatment effects and
      other risk factors were estimated. RESULTS: Twenty-nine patients presented with
      endophthalmitis, of whom 20 were classified as having proven infective
      endophthalmitis. The absence of an intracameral cefuroxime prophylactic regimen
      at 1 mg in 0.1 mL normal saline was associated with a 4.92-fold increase (95%
      confidence interval [CI], 1.87-12.9) in the risk for total postoperative
      endophthalmitis. In addition, the use of clear corneal incisions (CCIs) compared
      to scleral tunnels was associated with a 5.88-fold increase (95% CI, 1.34-25.9)
      in risk and the use of silicone intraocular lens (IOL) optic material compared to
      acrylic with a 3.13-fold increase (95% CI, 1.47-6.67). The presence of surgical
      complications increased the risk for total endophthalmitis 4.95-fold (95% CI,
      1.68-14.6), and more experienced surgeons were more likely to be associated with
      endophthalmitis cases. When considering only proven infective endophthalmitis
      cases, the absence of cefuroxime and the use of silicone IOL optic material were
      significantly associated with an increased risk, and there was evidence that men
      were more predisposed to infection (OR, 2.70; 95% CI, 1.07-6.8). CONCLUSIONS: Use
      of intracameral cefuroxime at the end of surgery reduced the occurrence of
      postoperative endophthalmitis. Additional risk factors associated with
      endophthalmitis after cataract surgery included CCIs and the use of silicone
      IOLs.

PMID- 17531691
TI  - Topical anesthesia: possible risk factor for endophthalmitis after cataract
      extraction.
AB  - PURPOSE: To assess the relationship between the risk for acute endophthalmitis
      after cataract extraction and whether certain factors, such as surgeon
      qualification, numerical order, duration of surgery, operating theater, and type
      of anesthesia (topical or retrobulbar), could be modified to decrease the risk.
      SETTING: Single-center academic practice. METHODS: Two epidemiological studies
      were performed: a case-control study and a retrospective cohort study. The
      surgical records of all patients with clinically diagnosed endophthalmitis within
      30 days after cataract surgery performed between February 2002 and September 2003
      were reviewed. The endophthalmitis cases were compared with 108 randomly selected
      controls (4 controls per case). The global incidence of endophthalmitis and the
      incidence according to type of anesthesia were calculated. RESULTS: Of 5011
      cataract extractions performed, 27 cases of endophthalmitis occurred. The
      incidence was 5.39 per 1000 procedures. An independent statistically significant
      relationship was found between endophthalmitis and the use of topical anesthesia
      (odds ratio [OR], 11.8; 95% confidence interval [CI], 2.4-58.7) and surgery
      longer than 45 minutes (OR, 7.2; 95% CI, 1.7-29.7) but not between the other
      variables. The incidence of endophthalmitis was 1.8 per 1000 cataract extractions
      with retrobulbar anesthesia and 6.76 per 1000 with topical anesthesia (relative
      risk [RR], 3.76; 95% CI, 0.89-15.85). After the start of the study period was
      extended to May 2001, the incidence of endophthalmitis was 1.3 per 1000 cataract
      extractions with retrobulbar anesthesia and 8.7 per 1000 with topical anesthesia
      (RR, 6.72; 95% CI, 1.63-27.63). CONCLUSION: Results suggest that there may be an
      association between topical anesthesia and endophthalmitis after cataract
      extraction.

PMID- 17531692
TI  - New approach for treating vertical strabismus: decentered intraocular lenses.
AB  - PURPOSE: To evaluate a new surgical procedure that uses a decentered intraocular
      lens (IOL) to correct vertical strabismus in cataract patients. SETTING:
      Department of Ophthalmology, Kitasato University School of Medicine, Sagamihara,
      Japan. METHODS: Six patients (11 eyes) with vertical strabismus had small
      incision cataract surgery. The continuous curvilinear capsulorhexis was
      decentered, and the asymmetrical span of the IOL haptics located on the side to
      be bent was inserted after phacoemulsification and aspiration. Some relaxing
      incisions were made in the anterior capsule. Postoperatively, the alternate prism
      cover test was used to assess changes in ocular position. In addition, the EAS
      1000 (Nidek) and KR-9000PW (Topcon) were used to evaluate IOL decentration, tilt,
      and aberrations. RESULTS: The mean age of the patients was 66 years (range 58 to
      77 years). The mean preoperative vertical strabismus was 7.3 prism diopters (PD)
      (range 4 to 12 PD). Two years after surgery, the mean angle of vertical deviation
      was 1.3 PD (range 0 to 5 PD) without affectivity coma-like aberrations (S3). The
      mean amount of decentration was 0.52 mm +/- 0.29 (SD) and the mean tilt, 4.30 +/-
      2.85 degrees (n = 10 eyes). CONCLUSION: Decentered IOL implantation was effective
      in cataract patients with vertical strabismus and can be performed during
      cataract surgery.

PMID- 17531693
TI  - Fitting behaviors of Fourier transform and Zernike polynomials.
AB  - PURPOSE: To evaluate the residual fit errors for wavefront measurements and
      corneal surfaces in virgin and post-surgery eyes using the Fourier transform and
      Zernike 6th- and 10th-order expansions. METHODS: Using MatLab (The MathWorks,
      Inc.) and VOLCT program (Sarver and Associates, Inc.), wavefront gradient fields
      derived from the Hartmann-Shack lenslet array of the CustomVue System (Visx,
      Inc.) and the corneal surface obtained from the Humphrey Atlas topographer (Carl
      Zeiss, Inc.) were fitted with the Fourier transform and Zernike 6th- and 10th
      order expansions. The wavefront gradient fields and corneal surfaces
      reconstructed by the 3 methods were compared with original ones, and the residual
      fit errors were analyzed (6.0 mm pupil). Ten eyes in each of the 4 groups (virgin
      eyes, post-laser in situ keratomileusis (LASIK) for myopia, post-LASIK for
      hyperopia, and post-radial keratotomy) were included. RESULTS: Wavefront gradient
      fields reconstructed with Fourier transform produced significantly smaller
      residual fit errors than Zernike 6th-order in all groups and Zernike 10th-order
      in all eyes except post-myopic-LASIK eyes. In all groups, wavefront gradient
      fields reconstructed with Zernike 10th order yielded significantly smaller
      residual errors than Zernike 6th order (all P<.05). Higher residual errors were
      produced by these 3 methods in more highly aberrated eyes. When corneal surfaces
      for all groups were reconstructed, the Fourier transform produced significantly
      lower residual fit errors than Zernike 6th order and 10th order and the Zernike
      10th order yielded significantly lower residual errors than Zernike 6th order
      (all P<.05). As corneal higher-order aberrations increased, higher residual
      surface fit errors were produced by Zernike 6th-order and 10th-order expansions
      but not by Fourier transform. CONCLUSIONS: Fourier transform reconstructed ocular
      wavefront and corneal topographic maps more accurately than Zernike polynomials
      up to the 10th order. Clinical implications require further study.

PMID- 17531694
TI  - Riboflavin and ultraviolet A collagen crosslinking: in vivo thermographic
      analysis of the corneal surface.
AB  - PURPOSE: To assess the possible thermal damage to the cornea during combined
      riboflavin and ultraviolet-A crosslinking using in vivo surface thermographic
      analysis. SETTING: Department of Oto-Neuro-Ophthalmological Surgical Sciences,
      Eye Clinic, University of Florence, Florence, Italy. METHODS: Collagen
      crosslinking was performed on a day-surgery basis under aseptic conditions with
      traditional techniques. During the procedure, temperature measurements on the
      corneal surface were taken using an infrared thermocamera. The temperature values
      were detected in the area directly exposed to light irradiation, selecting it in
      the acquired thermographic image. Because the aim of the study was to consider
      the thermal damage that may be induced during the procedure, the maximum
      temperature value detected in the area studied was recorded and considered for
      successive analysis. RESULTS: Infrared thermocamera measurements of the corneal
      surface during crosslinking treatment showed that the temperature was constant
      during the entire procedure and remains under the threshold of thermal injury to
      corneal collagen. CONCLUSION: Corneal collagen crosslinking was a safe procedure
      that did not cause thermal injury to the corneal surface.

PMID- 17531695
TI  - Effect of mitomycin-C on the corneal endothelium during excimer laser surface
      ablation.
AB  - PURPOSE: To study the effects of mitomycin-C (MMC) on the corneal endothelium
      after surface ablation. METHODS: This prospective observer-masked study comprised
      40 consecutive patients (80 eyes) scheduled to have laser-assisted subepithelial
      keratectomy (LASEK) to correct myopia. The patients were divided into 2 groups.
      Group 1 included 32 eyes in which the ablation depth was 50 mum or less and that
      received no MMC. Group 2 included 48 eyes in which the ablation depth exceeded 50
      mum and were treated with intraoperative MMC 0.02% for 30 seconds over the
      ablated zone. Preoperatively and 3 months postoperatively, 3 photographs of the
      central cornea of each eye were obtained using specular microscopy. A masked
      observer evaluated the endothelial cell density and compared the results between
      groups and the preoperative versus the postoperative results within the same
      group. RESULTS: The mean patient age was 31.5 years +/- 4.6 (SD) in Group 1 and
      33.2 +/- 7.9 years in Group 2 (P = .3). Within-group comparison between the
      preoperative and postoperative endothelial cell density values showed a
      statistically significant increase in both groups. The mean values in Group 1
      were 2462.5 +/- 226.8 cells/mm(2) preoperatively and 2562.5 +/- 258.7 cells/mm(2)
      postoperatively (P = .0001). The means in Group 2 were 2466.6 +/- 294.1
      cells/mm(2) and 2525 +/- 312.5 cells/mm(2), respectively (P = .0008). The
      differences in endothelial cell counts between Group 1 and Group 2 preoperatively
      and postoperatively were not statistically significant (P = .9 and P =.5,
      respectively). CONCLUSION: A single intraoperative application of MMC 0.02% for
      30 seconds after laser surface ablation did not seem to cause a substantial
      change in corneal endothelial cell density.

PMID- 17531696
TI  - Comparative study of coaxial phacoemulsification and microincision cataract
      surgery. One-year follow-up.
AB  - PURPOSE: To evaluate the amount of ultrasound (US) used, best corrected visual
      acuity (BCVA), and corneal endothelial cell loss in bimanual microincision
      cataract surgery (MICS) and coaxial phacoemulsification. SETTING: Department of
      Ophthalmology, Universidade Gama Filho, Rio de Janeiro, Brazil. METHODS: A
      prospective randomized study included 30 patients (60 eyes) with bilateral
      cataract. All patients had coaxial phacoemulsification in 1 eye and MICS in the
      fellow eye. The US time and the effective US time were measured intraoperatively.
      The BCVA and central endothelial cell loss were evaluated in both groups over a 1
      year follow-up. The results between the 2 groups were compared. RESULTS: The
      total US time was lower in the coaxial phacoemulsification group than in the MICS
      group; the means were 0.50 minutes +/- 0.33 (SD) and 0.82 +/- 0.39 minutes,
      respectively. The mean US power was similar between groups (mean 10.1% +/- 3.76%
      and 10.0% +/- 4.0%, respectively). The BCVA was similar between the groups from
      24 hours to 1 year. The mean central corneal endothelial cell loss at 3 months
      was 4.66% +/- 6.10% in the coaxial phacoemulsification group and 4.45% +/- 5.06%
      in the MICS group and at 1 year, 6.00% +/- 6.72% and 8.82% +/- 7.39%,
      respectively. The only significant difference in the postoperative results
      between the 2 groups was central endothelial cell loss at the 1-year follow-up.
      CONCLUSIONS: The US time was longer in the MICS group than in the in the coaxial
      phacoemulsification group, but the mean US power was similar between groups. The
      BCVA was also similar between groups; however, the MICS group had more central
      endothelial cell loss at the 1-year follow-up.

PMID- 17531697
TI  - Intraoperative performance and postoperative outcomes of microcoaxial
      phacoemulsification. Observational study.
AB  - PURPOSE: To evaluate the intraoperative performance and postoperative outcomes
      after microcoaxial phacoemulsification. SETTING: Iladevi Cataract & IOL Research
      Centre, Ahmedabad, India. METHODS: A prospective observational case series
      comprised 84 eyes with age-related uncomplicated cataract having microcoaxial
      phacoemulsification through a 2.2 mm clear corneal incision by a standard
      surgical technique. Phacoemulsification parameters (Infiniti Vision System,
      Alcon) were microburst width, 30 ms; preset power, 50%; vacuum, 650 mm Hg;
      aspiration flow rate, 25 cc/minute. A single-piece Alcon AcrySof intraocular lens
      was implanted with the C cartridge (Alcon) cartridge. The incision was measured
      at the end of surgery. Observations included surgical time (from commencement of
      sculpting to end of epinucleus removal), cumulative dissipated energy (CDE),
      wound burns, intraoperative complications, postoperative increase in mean central
      corneal thickness (CCT) at 1 day and 1 month, mean % decrease in endothelial cell
      density (ECD), absolute mean change in coefficient of variation (cv) 3 months,
      and uncorrected visual acuity (UCVA) at 1 day. Data were analyzed using a 1
      sample t test with 95% confidence intervals (CIs). RESULTS: The mean follow up
      was 3 months +/- 0.3 (SD). The mean incision size at the end of surgery was 2.3
      +/- .09 mm; mean surgical time, 4.5 +/- 1.5 minutes; and mean CDE, 2.3 +/- 2.2
      seconds. No wound burns or other intraoperative complications occurred. The
      postoperative CCT increased by a mean of 16 microm at 1 day (95% CI, 8-25; P =
      .66;) and by a mean of 3.14 microm at 1 month (95% CI, 2.26-4.05; P = .92). The
      ECD decreased by a mean of 5.8% (95% CI, 6.8-3.5; P = .82) and the mean
      coefficient of variation, by 3.3 (95% CI, 4.5-2.0; P = .65). At 1 day, the UCVA
      was 20/20 in 29% of cases, 20/20 to 20/40 in 58%, and 20/40 to 20/50 in 12%.
      CONCLUSION: Microcoaxial phacoemulsification was safely and effectively
      performed, achieving consistent and satisfactory postoperative outcomes.

PMID- 17531698
TI  - Low-intensity ultraviolet A irradiation of the lens capsule to remove lens
      epithelial cells during cataract surgery. Effectiveness and safety.
AB  - PURPOSE: To assess the effectiveness and safety of low-intensity ultraviolet A
      (UVA) irradiation in removing lens epithelial cells (LECs) during cataract
      surgery and compare them with those of mechanical polishing and no treatment.
      SETTING: Eyecove Ophthalmology Clinics, Pune, India. METHODS: This prospective
      randomized double-masked study consisted of preoperative screening of 36
      patients, of which 30 met the inclusion criteria and were recruited. The patients
      had routine cataract surgery. A bean-shaped capsulorhexis was performed. After
      the nucleus and cortex were removed, the capsular bag was irradiated from inside
      with low-intensity UVA in 1 group. A second group had mechanical polishing, and a
      third group was not treated. A small flap of the anterior capsule was removed in
      each patient. The flap was stained and mounted in a Fuchs-Rosenthal chamber. For
      estimation of effectiveness, the area of capsule covered with epithelial cells
      was estimated by examination under a light microscope. One day postoperatively,
      an examination was performed to assess the safety of each technique. RESULTS: The
      area of the capsule from which the LECs were removed was significantly larger in
      the UVA-irradiation group than in the mechanical-polishing group (P = .001) and
      the no-treatment group (P = .001). There was no significant difference between
      the mechanical-polishing and no-treatment groups (P>.05). The area of the capsule
      flap that was covered with LECs was significantly less in the UVA-irradiation
      group than in the mechanical-polishing group (P = .017) and the no-treatment
      group (P = .001). The mechanical-polishing group and no-treatment group were not
      significantly different from each other (P>.05). Corneal edema was significantly
      less in the UVA-irradiation group than in the mechanical-polishing group (P<.001)
      and no-treatment group (P = .012). No patient in the UVA-irradiation group had
      postoperative lid edema; 8 patients in each of the other 2 groups had lid edema.
      The difference was statistically significant (P<.0001). Pupil size was
      significantly larger in the UVA-irradiation group than in the mechanical
      polishing group and no-treatment group; the difference was significant (both P =
      .0001). There was no significant difference in pupil size in the mechanical
      polishing group and no-treatment group. No significant difference was observed
      between the 3 groups in visual acuity, conjunctival edema, anterior chamber
      flare, and intraocular pressure. CONCLUSION: Ultraviolet A irradiation of the
      capsular bag was effective and safe in removing LECs from the anterior capsule
      during cataract surgery.

PMID- 17531699
TI  - Functional outcomes after implantation of Tecnis ZM900 and Array SA40 multifocal
      intraocular lenses.
AB  - PURPOSE: To evaluate the functional outcome after implantation of the Tecnis
      ZM900 multifocal intraocular lens (IOL) (AMO) and the Array SA40 multifocal IOL
      (AMO). SETTING: Department of Ophthalmology, Bundesknappschaft s Hospital,
      Sulzbach, and the Department of Ophthalmology, Marienhospital, Aachen, Germany.
      METHODS: In a prospective comparative 2-center trial, Tecnis ZM900 and the Array
      SA40 multifocal IOLs were bilaterally implanted in 50 patients (50 eyes Tecnis,
      50 eyes Array) by 1 surgeon at each center. The following parameters were
      assessed 30 to 60 days and 120 to 180 days after surgery in both eyes:
      refraction, pupil size, uncorrected and best corrected visual acuities for
      distance and near at different contrast levels, and photopic and mesopic contrast
      sensitivity at different spatial frequencies. Patient satisfaction (spectacle
      independence, photic phenomena, overall satisfaction) was assessed by a
      questionnaire. RESULTS: The main differences between the 2 multifocal IOLs were
      the better uncorrected near visual acuity (P<.001), distance-corrected near
      visual acuity (P<.001), the mesopic contrast sensitivity at high spatial
      frequencies (P<.05) as well as greater independence from spectacles in patients
      with the Tecnis multifocal IOL, resulting in higher levels of patient
      satisfaction. CONCLUSION: The aspherical diffractive Tecnis multifocal IOL gave
      better outcomes than the Array multifocal IOL.

PMID- 17531700
TI  - Scheimpflug imaging to determine intraocular lens power in vivo.
AB  - PURPOSE: To assess the feasibility of determining intraocular lens (IOL) power by
      measurement of the central optic thickness using clinically available Scheimpflug
      imaging (Pentacam, Oculus). SETTING: King's College Hospital Ophthalmology
      Department, London, United Kingdom. METHODS: Sixty-seven eyes were assessed 1
      month after uneventful phacoemulsification with in-the-bag implantation of
      AcrySof MA60AC IOLs (Alcon). The correlation between IOL thickness measurement
      and IOL power was calculated. Repeatability of central optic thickness
      measurement was determined from 10 successive scans of 4 patients. RESULTS:
      Within-subject standard deviation increased with the subject mean. The
      coefficient of variability was 1.4%. Measured lens thickness was highly
      correlated with lens power (R(2) = 0.94, P<.001). Over the measured range, 95%
      confidence intervals varied between +/-0.83 diopters (D) and +/-0.92 D.
      CONCLUSIONS: Central IOL thickness measurements with the Pentacam Scheimpflug
      camera were highly repeatable and closely correlated with the known IOL power.
      The IOL power, calculated from a regression equation, is likely to be less than
      +/-1.00 D away from the actual power. Approximate in vivo IOL power determination
      is feasible with clinically available Scheimpflug imaging. This could be applied
      clinically in cases of unexplained postoperative refractive error.

PMID- 17531701
TI  - Intraocular lens power calculation after radial keratotomy: estimating the
      refractive corneal power.
AB  - PURPOSE: To evaluate the most accurate method for corneal power determination in
      patients with previous radial keratotomy (RK). SETTING: University of Texas
      Southwestern Medical Center at Dallas, Dallas, Texas, USA. METHODS: A
      retrospective review of data for 16 eyes of 14 patients with a history of RK and
      subsequent phacoemulsification and posterior chamber intraocular lens (IOL)
      implantation was performed. Outcome measures included axial length, postoperative
      topography, type and power of IOL implanted, and postoperative spherical
      equivalent (SE) refraction at 3 to 6 months. Average central corneal power (ACCP)
      was defined as the average of the mean powers of the central Placido rings. For
      each eye, simulated K-readings and different values of ACCP computed
      corresponding to different central corneal diameters were used in each case,
      along with the implanted IOL power, to back-calculate the SE refraction (Ref) via
      the double-K adjusted Holladay 1 IOL formula. The predicted refractive error was
      hence computed as (Ref - SE), both in algebraic and absolute values. RESULTS: The
      ACCP over the central 3.0 mm (ACCP(3mm)) yielded the lowest absolute predicted
      refractive error (0.25 +/- 0.38 diopters [D]), which was statistically lower than
      the error for ACCP(1mm) (P<.001) and for the simulated K-value (P = .033). It
      also resulted in 87.5% of eyes being within +/-0.50 D and 100% within +/-1.00 D
      of the actual postoperative refraction. CONCLUSIONS: Corneal refractive power
      after RK was best described by averaging the topographic data of the central 3.0
      mm area. Applying this method, together with a double-K IOL formula, achieved
      excellent IOL power predictability.

PMID- 17531702
TI  - Photorefractive keratectomy in the cat eye: biological and optical outcomes.
AB  - PURPOSE: To quantify optical and biomechanical properties of the feline cornea
      before and after photorefractive keratectomy (PRK) and assess the relative
      contribution of different biological factors to refractive outcome. SETTING:
      Department of Ophthalmology, University of Rochester, Rochester, New York, USA.
      METHODS: Adult cats had 6.0 diopter (D) myopic or 4.0 D hyperopic PRK over 6.0 or
      8.0 mm optical zones (OZ). Preoperative and postoperative wavefront aberrations
      were measured, as were intraocular pressure (IOP), corneal hysteresis, the
      corneal resistance factor, axial length, corneal thickness, and radii of
      curvature. Finally, postmortem immunohistochemistry for vimentin and alpha-smooth
      muscle actin was performed. RESULTS: Photorefractive keratectomy changed ocular
      defocus, increased higher-order aberrations, and induced myofibroblast
      differentiation in cats. However, the intended defocus corrections were only
      achieved with 8.0 mm OZs. Long-term flattening of the epithelial and stromal
      surfaces was noted after myopic, but not after hyperopic, PRK. The IOP was
      unaltered by PRK; however, corneal hysteresis and the corneal resistance factor
      decreased. Over the ensuing 6 months, ocular aberrations and the IOP remained
      stable, while central corneal thickness, corneal hysteresis, and the corneal
      resistance factor increased toward normal levels. CONCLUSIONS: Cat corneas
      exhibited optical, histological, and biomechanical reactions to PRK that
      resembled those previously described in humans, especially when the OZ size was
      normalized to the total corneal area. However, cats exhibited significant stromal
      regeneration, causing a return to preoperative corneal thickness, corneal
      hysteresis and the corneal resistance factor without significant regression of
      optical changes induced by the surgery. Thus, the principal effects of laser
      refractive surgery on ocular wavefront aberrations can be achieved despite clear
      interspecies differences in corneal biology.

PMID- 17531703
TI  - Contact inhibition of migrating lens epithelial cells at the capsular bend
      created by a sharp-edged intraocular lens after cataract surgery.
AB  - PURPOSE: To investigate whether the lens epithelial cells (LECs) at the capsular
      bend created by a sharp-edged intraocular lens (IOL) are in the G(0) phase of the
      cell cycle. SETTING: Nishi Eye Hospital, Osaka, Japan. METHOD: A CeeOn Edge
      silicone IOL (AMO) with sharp edges was implanted in 1 eye and a PhacoFlex II
      silicone IOL (AMO) with rounded edges in the contralateral eye after standard
      cataract surgery in 6 rabbits. Immunohistochemical staining for the Ki-67
      antibody was performed 1 day, 3, 4, and 7 weeks after surgery. RESULTS: In eyes
      with the sharp-edged IOL, LECs with thin, elongated nuclei accumulated at, but
      did not extend beyond, the capsular bend and stained negative for the Ki-67
      antibody, indicating that they were in the G(0) phase of the cell cycle. In
      contrast, in the eye with the round-edged IOL, continuous migration of a
      predominantly monolayer of LECs over the IOL and onto the posterior capsule
      occurred. These cells were Ki-67 positive, indicating that they were
      proliferating. CONCLUSIONS: Lens epithelial cells at the capsular bend of sharp
      edged IOLs were in the G(0) phase of the cell cycle, indicating that they were
      contact inhibited. These findings support the theory the sharp posterior optic
      edge of the IOL inhibits LEC migration, reducing formation of posterior capsule
      opacification. Whether these LECs can reactivate when the capsular bend is
      eliminated by later formation of a Soemmerring's ring requires further studies.

PMID- 17531704
TI  - Efficacy of Cruise Control in controlling postocclusion surge with Legacy and
      Millennium venturi phacoemulsification machines.
AB  - PURPOSE: To determine the efficacy of the Cruise Control surge-limiting device
      (Staar Surgical) with phacoemulsification machines known to have high levels of
      surge. SETTING: John A. Moran Eye Center Clinical Laboratories. METHODS: In an in
      vitro study, postocclusion anterior chamber depth changes were measured in fresh
      phakic human eye-bank eyes using the Alcon Legacy and Bausch & Lomb Millennium
      venturi machines in conjunction with the Staar Cruise Control device. Both
      machines were tested with 19-gauge non-Aspiration Bypass System tips at high
      surge settings (500 mm Hg vacuum pressure, 75 cm bottle height, 40 mL/min flow
      rate for the Legacy) and low-surge settings (400 mm Hg vacuum pressure, 125 cm
      bottle height, 40 mL/min flow rate for the Legacy). Adjusted parameters of flow,
      vacuum, and irrigation were used based on previous studies to create identical
      conditions for each device tested. The effect of the Cruise Control device on
      aspiration rates was also tested with both machines at the low-surge settings.
      RESULTS: At the high setting with the addition of Cruise Control, surge decreased
      significantly with the Legacy but was too large to measure with the Millennium
      venturi. At the low setting with the addition of Cruise Control, surge decreased
      significantly with both machines. Surge with the Millennium decreased from more
      than 1.0 mm to a mean of 0.21 mm +/- 0.02 (SD) (P<.0001). Surge with the Legacy
      decreased from a mean of 0.09 +/- 0.02 mm to 0.05 +/- 0 mm, a 42.9% decrease
      (P<.0001). The Millennium had the highest surge and aspiration rate before Cruise
      Control and the greatest percentage decrease in the surge and aspiration rates as
      a result of the addition of Cruise Control. CONCLUSIONS: In the Legacy machine,
      the Cruise Control device had a statistically and clinically significant effect.
      Cruise Control had a large effect on fluidics as well as surge amplitude with the
      Millennium machine. The greater the flow or greater the initial surge, the
      greater the impact of the Cruise Control device.

PMID- 17531705
TI  - Development of an in vitro model to assess posterior capsule safety during
      phacoemulsification with ultrasound or AquaLase handpieces.
AB  - PURPOSE: To develop a cadaver eye model that would assess posterior capsule (PC)
      vulnerability when different cataract removal technologies were evaluated and use
      the model to evaluate the relative amplitude levels required to rupture the human
      PC with the AquaLase handpiece (Alcon) compared with an ultrasound (US)
      handpiece. SETTING: Private practice, Cincinnati, Ohio, USA. METHODS: In part 1
      of the study, 26 phakic human cadaver eyes were sectioned in the anteroposterior
      meridian. The anterior portion of the globe was placed cornea side down, and the
      vitreous was gently cleared from the posterior surface of the lens capsule.
      Ultrasound was applied directly to the central capsule after achieving a vacuum
      of 100 mm Hg. The power was incremented until rupture was observed. In part 2 of
      the study, the same procedure was repeated with 50 eye pairs. For each pair, US
      was randomly applied to 1 eye and AquaLase to the other. The 50 pairs were
      divided into 3 groups based on vacuum level: 100, 300, or 500 mm Hg. RESULTS:
      Part 1 results show that at 100 mm Hg, the mean power needed to break the PC with
      US was 19% +/- 6% (SD). There was no correlation between time from harvest to
      test and rupture power (R(2) = 0.04) or between donor age and rupture power (R(2)
      = 0.2). When the same procedure was repeated in part 2, on average, US power
      ruptured the capsule at a lower power than the AquaLase magnitude at each vacuum
      setting. The respective means were 18.5% +/- 6.7% and 61.0% +/- 23.3% for 100 mm
      Hg, 15.2% +/- 5.4% and 47.1% +/- 14.5% for 300 mm Hg, and 11.8% +/- 6.5% and
      20.0% +/- 9.4% for 500 mm Hg. The difference between the groups and the values
      within each group decreased as vacuum levels increased. CONCLUSION: This new
      experimental model in a cadaver eye provides a useful method for comparing
      factors and techniques that contribute to PC rupture.

PMID- 17531706
TI  - Far and near visual acuity with multifocal intraocular lenses in an
      optomechanical eye model with imaging capability.
AB  - PURPOSE: To compare the quantitative and qualitative visual performances of
      different multifocal intraocular lenses (IOLs) in an experimental model of the
      human eye. SETTING: University Hospital San Raffaele, Milan, Italy. METHODS: Five
      multifocal IOLs and 1 monofocal IOL were implanted in an optomechanical eye model
      with imaging capability. The comparative optical characterization of the imaging
      performance included aberrometry, simulated visual acuity testing at variable
      contrast for far and near distance, glare tests, and image records of optotype
      charts. RESULTS: The maximum recorded far visual acuity for the monofocal IOL was
      between 20/12.5 and 20/16; the multifocal IOLs decreased visual acuity by 1 to 2
      lines. The difference tended to increase at reduced contrast. Full-contrast near
      visual acuity with multifocal IOLs ranged between 20/63 and 20/25; the near
      distance performance of the monofocal IOL without an additional correcting lens
      was worse by 1 to 3 lines of acuity with large pupils but was comparable with
      small pupils. Multifocal IOLs of different designs showed marked differences as a
      function of contrast, which tended to balance between far and near behaviors.
      CONCLUSIONS: Multifocal IOLs of different optical designs were well characterized
      and distinguished by simulated contrast acuity testing in an experimental eye
      model, allowing quantitative comparison. Their overall visual performance,
      averaged over contrast and distance, was not superior to the performance of a
      monofocal IOL without an additional correcting lens.

PMID- 17531707
TI  - Recommended practices for cleaning and sterilizing intraocular surgical
      instruments.

PMID- 17531708
TI  - Bilateral cystoid macular edema after phacoemulsification in post-laser in situ
      keratomileusis eyes.
AB  - We report a case of a 66-year-old man who had bilateral laser in situ
      keratomileusis and 6 months later, uneventful simultaneous bilateral cataract
      surgery. One week postoperatively, the visual acuity was reduced and 4 weeks
      later, the patient was referred to our clinic with a macular hemorrhage in the
      right eye and bilateral cystoid macular edema. He was treated with bilateral sub
      Tenon's triamcinolone, which had to be repeated in both eyes, and is still being
      followed.

PMID- 17531709
TI  - Suprachoroidal hemorrhage following removal of releasable suture after combined
      phacoemulsification-trabeculectomy.
AB  - We report a case of suprachoroidal hemorrhage following removal of a releasable
      suture after combined phacoemulsification-trabeculectomy.

PMID- 17531711
TI  - Intraoperative floppy-iris syndrome: do we know everything about it?
AB  - We report a case of bilateral phacoemulsification for nuclear cataract in a 76
      year-old man. The patient took tamsulosin for 4 months and stopped the medication
      1 year before the cataract surgery. Phacoemulsification in the left eye was
      uneventful. One week later, phacoemulsification was performed in the same manner
      in the right eye, which demonstrated the 3 signs of the intraoperative floppy
      iris syndrome (IFIS). Postoperative examinations revealed iris stromal atrophy
      and an irregular pupil in this eye. This case raises many questions: Why was IFIS
      seen in 1 eye only? Is the intake and stopping time of tamsulosin important to
      the occurrence of IFIS? Is intracameral adrenaline effective in preventing IFIS?
      Future studies are needed to increase our understanding of IFIS.

PMID- 17531710
TI  - Pigmentary dispersion syndrome with a secondary piggyback 3-piece hydrophobic
      acrylic lens. Case report with clinicopathological correlation.
AB  - We describe a case of pigmentary dispersion syndrome resulting from secondary
      piggyback implantation of a 3-piece hydrophobic acrylic squared-edged intraocular
      lens (IOL) in the ciliary sulcus. The intraocular pressure remained elevated
      despite pharmacological treatment, with a heavily pigmented trabecular meshwork.
      The piggyback IOL was subsequently explanted and replaced by a silicone IOL with
      smooth round edges. Examination of the explanted IOL under light and scanning
      electron microscopy showed clusters of pigment epithelial cells located around
      the periphery of the anterior optic surface.

PMID- 17531712
TI  - Regression of neovascular posterior capsule vessels by intravitreal bevacizumab.
AB  - We present a 76-year-old woman who developed neovascularization of the posterior
      capsule 1 year after extracapsular cataract extraction. She had type 2 diabetes
      for 15 years, with proliferative diabetic retinopathy that had been treated with
      panretinal photocoagulation. The neovascular vessels on the posterior capsule
      originated from existing rubeosis iridis and regressed after a single injection
      of intravitreal bevacizumab (Avastin). The patient's visual acuity increased to
      20/40 after an uneventful neodymium:YAG capsulotomy.

PMID- 17531713
TI  - Unilateral electric cataract: Scheimpflug imaging and review of the literature.
AB  - A 22-year-old man presented with diminution of vision in the left eye 1 month
      after sustaining an injury from a high-voltage electric current to the left side
      of his head. Slitlamp examination and Scheimpflug imaging confirmed the typical
      anterior subcapsular lenticular opacities in the left eye and also documented
      early anterior subcapsular vacuoles in the right eye. Based on history, the
      electric shock wound, and the typical appearance of the opacities, an electric
      cataract was diagnosed. The difference in lens density between the 2 eyes was
      also documented. The best corrected visual acuity (BCVA) was 20/20 in the right
      eye and counting fingers at 1 foot in the left eye. Phacoaspiration and posterior
      chamber intraocular lens implantation were performed in the left eye.
      Postoperatively, the BCVA improved to 20/20. The developmental mechanisms of
      these opacities after exposure to an electric current and the role of Scheimpflug
      imaging in assessing the earliest subclinical manifestations of electric cataract
      injuries are discussed.

PMID- 17531714
TI  - Contrast sensitivity loss in the peripheral visual field following laser in situ
      keratomileusis.
AB  - We report a case of contrast sensitivity loss in the peripheral visual field
      following laser in situ keratomileusis (LASIK). A 50-year-old white man was
      referred to us for differences in visual perception in the peripheral field
      between the right eye, which had had LASIK, and the left eye, which was
      emmetropic. Linear meridional static perimetry was carried out in the 0- to 180
      degree meridian using a Goldmann perimeter to assess the peripheral perimetric
      thresholds. There was a statistically significantly marked increased threshold in
      contrast sensitivity in the nasal and temporal fields from 40 degrees of
      eccentricity in the LASIK eye compared with that in the emmetropic eye. Eyes
      treated with LASIK may show higher peripheral thresholds than untreated eyes
      owing to poorer retinal image quality after LASIK surgery. Excimer laser surgeons
      should consider optical factors when post-LASIK patients complain of peripheral
      visual field symptoms.

PMID- 17531715
TI  - Hyperplastic persistent pupillary membranes with congenital corneal anomalies.
AB  - We report a case of a 14-year-old girl who presented with impaired vision in the
      left eye since birth. Examination showed extensive bilateral persistent pupillary
      membranes associated with microcornea, cornea plana, and central localized
      posterior keratoconus in both eyes. The uncorrected visual acuity was 0.2
      (logMAR) (20/32) in the right eye and 1.9 (logMAR) (20/1300) in the left eye,
      with no improvement with pinhole. Surgical excision of the membranes was done in
      both eyes using vitreous microscissors. At 6 months, the best corrected visual
      acuity was 0.1 (logMAR) (20/25) in the right eye and 1.3 (logMAR) (20/400) in the
      left eye. No significant intraoperative or postoperative complications were
      noted.

PMID- 17531716
TI  - Phacoemulsification and intraocular lens implantation in Alport syndrome with
      anterior lenticonus.
AB  - Eleven eyes of 6 patients with Alport syndrome had phacoemulsification with
      implantation of a single-piece acrylic hydrophobic intraocular lens (IOL)
      (AcrySof SA6OAT, Alcon) because of anterior lenticonus. All patients had
      excellent visual acuity after surgery. We recommend phacoemulsification with IOL
      implantation as a safe and effective procedure in patients with anterior
      lenticonus secondary to Alport syndrome.

PMID- 17531717
TI  - Photodynamic therapy for posterior capsule neovascularization.
AB  - We report a 71-year-old man with posterior capsule opacification with severe
      neovascularization who was treated with photodynamic therapy and neodymium:YAG
      capsulotomy. Treatment was performed using a diode laser at 692 nm, a light dose
      of 50 J/cm(2), and 6 mg/m(2) body surface area verteporfin. The initial visual
      acuity was hand motions; 6 months after therapy, the visual acuity was stable at
      20/200. In 9 months of follow-up, there was no recurrence of neovascularization
      and the pupil area remained clear; no retreatment was needed. Photodynamic
      therapy provided safe and effective occlusion of neovascular vessels in the
      posterior capsule area.

PMID- 17531718
TI  - Prevention of posterior capsule opacification using round-edged PMMA IOL.

PMID- 17531719
TI  - Persistent anterior chamber gas bubbles during IntraLASIK.

PMID- 17531720
TI  - Effect of trypan blue on lens epithelial cells in human eyes having
      capsulorhexis.

PMID- 17531721
TI  - Intermittent corneal edema due to anterior segment retained lens fragments.

PMID- 17531722
TI  - Fever, epidurals, and inflammation: a burning issue.

PMID- 17531723
TI  - Activin betaA in term placenta and its correlation with placental inflammation in
      parturients having epidural or systemic meperidine analgesia: a randomized study.
AB  - STUDY OBJECTIVE: To investigate the immunohistochemical localization of betaA
      subunit of activin A in human term placenta, as a marker for placental
      infection/inflammation and elevated temperature, in parturients laboring during
      two analgesic regimens. DESIGN: Prospective, randomized controlled study.
      SETTING: Delivery room. PATIENTS: 56 healthy, ASA physical status I and II
      primiparous women in labor. INTERVENTIONS: Parturients were assigned to receive
      patient-controlled epidural analgesia (PCEA) with 0.2% ropivacaine or patient
      controlled intravenous analgesia PCA with meperidine. MEASUREMENTS: Histologic
      and immunohistochemical placental evaluation for white blood cell infiltration
      and activin betaA staining were made. Maternal temperature elevation above 37.6
      degrees C and leukocytosis above 15,000/microL were recorded. MAIN RESULTS:
      Temperature was not significantly increased in parturients receiving PCEA over
      those who received (PCA) with meperidine (31% vs 11%, respectively; P = 0.1).
      There was also no association between temperature elevation during epidural
      analgesia and increased white blood cell count (>15,000/microL) or presence of
      polymorphonuclear and/or lymphocyte aggregation in the placenta.
      Immunohistochemical staining with antisera against the betaA subunit of activin
      was present mainly in the placental cytotrophoblast, syncytiotrophoblast, and
      vascular endothelium, and was not associated with an increase in maternal
      temperature. No significant difference was noted between the two analgesic
      techniques with regard to maternal temperature elevation. Intrapartum temperature
      elevation was not associated with histologic signs of placental inflammation or
      with expression of activin betaA in the placenta. CONCLUSION: Other mechanisms
      may be involved in the etiology of temperature elevation during labor.

PMID- 17531724
TI  - Evaluation of a new fenestrated needle for ultrasound-guided fascia iliaca block.
AB  - STUDY OBJECTIVE: To evaluate a new 20-gauge (G) fenestrated needle designed to be
      used with ultrasound guidance to deliver local anesthetic into the tissue plane
      of the fascia iliaca without immediate proximity to the femoral nerve. DESIGN:
      Prospective study. SETTING: University hospital. PATIENTS: 15 male volunteers.
      INTERVENTIONS: To determine the onset of motor and sensory block after ultrasound
      guided injection of 1% lidocaine and iopamidol, fluoroscopy was performed during
      and after injection to discover the pattern of local anesthetic distribution. The
      buckling strength of the new needle was compared using a standard mechanical
      testing protocol to a conventional 22-G needle (Quincke type). MEASUREMENTS AND
      MAIN RESULTS: Injection through the fenestrated needle consistently produced
      sensory block in the anterior, medial, and lateral aspects of the thigh. All
      subjects were also observed to have loss of motor function in the quadriceps
      muscle. No subject experienced motor effect in the adductor muscles of the thigh.
      The fenestrated 20-G needle yielded at significantly larger compressive forces
      than did the standard 22-G needle (P < 0.001). CONCLUSION: The needle is novel in
      that it does not require immediate proximity to the femoral nerve or precise
      placement of the needle tip in the plane of the fascia iliaca. The 20-G
      fenestrated needle is stronger under compressive force than existing 22-G
      needles.

PMID- 17531725
TI  - The impact of isoflurane, desflurane, or sevoflurane on the frequency and
      severity of postoperative nausea and vomiting after lumbar disc surgery.
AB  - STUDY OBJECTIVE: To test the hypothesis that anesthesia with the low-soluble
      inhalation anesthetics, sevoflurane, and desflurane, may result in a lower
      frequency and severity of postoperative nausea and vomiting (PONV) than
      anesthesia with isoflurane. DESIGN: Prospective, observational study. SETTING:
      Postoperative care unit and neurosurgical ward at a university hospital.
      PATIENTS: 625 ASA physical status I, II, and III patients undergoing elective
      lumbar disc surgery with general anesthesia were included in this study.
      INTERVENTIONS: Patients were enrolled sequentially to receive either 0.7%-1.2%
      isoflurane (year 2002), 3.5%-5.5% desflurane (year 2003), or 1.2%-1.9%
      sevoflurane (year 2004) for maintenance of anesthesia without nitrous oxide.
      Study personnel, general anesthesia management, and surgical technique remained
      unchanged over the three-year study period. MEASUREMENTS: Occurrence of PONV
      within 24 hours of the end of surgery was recorded. Secondary outcome measures
      were occurrence of multiple PONV episodes, maximum severity, time to the first
      PONV event, need for rescue medication, difference between the occurrence of PONV
      (indicator variable) and the expected risk of PONV (based on the Apfel score).
      MAIN RESULTS: Type of inhalation anesthetic had no influence on PONV frequency
      (9.3%, 11.2%, and 10.8% after isoflurane, desflurane, and sevoflurane,
      respectively; P = 0.8) or its severity (numerical rating scale, 4.5 +/- 2.0, 4.4
      +/- 2.4, and 4.2 +/- 2.1; P = 0.9). Patients who received isoflurane experienced
      fewer early events but had a late peak of PONV frequency (P = 0.031). For every
      10 minutes by which the total duration of the anesthesia exceeded the net time
      between incision and suture, the risk of PONV increased by a factor of 1.36 (95%
      confidence interval, 1.15-1.61; P < 0.001). CONCLUSIONS: There is no difference
      between the three inhalation anesthetics currently used with regard to frequency
      or severity of postoperative nausea, vomiting, or both.

PMID- 17531726
TI  - High C-reactive protein and low cholesterol levels are prognostic markers of
      survival in severe sepsis.
AB  - STUDY OBJECTIVE: To evaluate serum C-reactive protein and cholesterol as a
      prognostic factor for survival in patients with severe sepsis. DESIGN:
      Prospective study. SETTING: University hospital. PATIENTS: The study population
      consisted of 96 patients (age range, 18-75 years; median, 56 years; men/women
      ratio, 40:56) in whom severe sepsis was diagnosed. INTERVENTIONS: Patients' serum
      levels of C-reactive protein and cholesterol were measured upon admission to an
      intensive care unit, two days later, and on the day of discharge from the
      intensive care unit or on the day of death. MEASUREMENTS AND MAIN RESULTS:
      Cholesterol levels were significantly lower among the nonsurviving patients (day
      1, 92.2 +/- 25.1 mg/dL; day 2, 92.1 +/- 21.7 mg/dL; death/discharge day, 92.2 +/-
      21.7 mg/dL) than surviving patients (day 1, 175.1 +/- 38.6 mg/dL [P < 0.001]; day
      2, 173.0 +/- 39.3 mg/dL [P < 0.001]; death/discharge day, 171.8 +/- 39.6 mg/dL [P
      = 0.010]). Median C-reactive protein levels were significantly higher among the
      nonsurvivors (day 1, 32 mg/dL [range, 20.5-64.5 mg/dL]; day 2, 33 mg/dL [range,
      22-74.5 mg/dL]; death/discharge day, 30 mg/dL [range, 22-57 mg/dL]) than
      survivors (day 1, 10 mg/dL [range, 6-14 mg/dL]; day 2, 9 mg/dL [range, 5-10
      mg/dL]; death/discharge day, 6 mg/dL [range, 3-9 mg/dL]; P < 0.001). CONCLUSION:
      Serum C-reactive protein and cholesterol are a predictor of survival in patients
      with severe sepsis. Low cholesterol and high C-reactive protein levels appear as
      a valuable tool for individual risk assessment in severe sepsis patients and for
      stratification of high-risk patients in future intervention trials.

PMID- 17531727
TI  - Massive blood transfusion in choroid plexus tumor surgery: 10-years' experience.
AB  - STUDY OBJECTIVE: To describe our 10 years of experience with childhood choroid
      plexus tumors (CPTs). DESIGN: Retrospective chart analysis. SETTING: Operating
      room and pediatric intensive care unit (PICU) of a university hospital. PATIENTS:
      18 infants and children undergoing CPT surgery from 1995 to 2004, 11 of whom were
      younger than 12 months. MEASUREMENTS: Perioperative hematologic and coagulation
      data were measured as well as estimated red cell volume variations (as a reliable
      index of blood loss) in the perioperative period, together with coagulation
      parameters. RESULTS: Greater blood loss was recorded in the infant group vs older
      children (percentage of estimated red cell volume loss, 1.31 +/- 1.79% vs 0.20 +/
      0.17% [P < 0.01] and 1.50 +/- 1.86% vs 0.29 +/- 0.21% [P < 0.01] on PICU
      admission and after 72 hours, respectively). Platelet count decrease was
      similarly noted (51.60 +/- 28.06 vs 27.57 +/- 11.98, P < 0.05, as percentage of
      preoperative count). Patients operated on in the neonatal period showed the
      highest blood loss and related coagulation impairment. CONCLUSION: Younger CPT
      surgery patients present an increased risk versus their older counterparts of
      massive bleeding resulting in hemodynamic instability and coagulative impairment.

PMID- 17531728
TI  - Identification of systematic underestimation (bias) of case durations during case
      scheduling would not markedly reduce overutilized operating room time.
AB  - STUDY OBJECTIVE: If a case has a high probability of taking longer than
      scheduled, then increasing the case's scheduled duration could reduce over
      utilized operating room (OR) time. We studied surgeons' and schedulers' case
      scheduling behavior to evaluate whether such a strategy would be useful. DESIGN:
      Observational study. SETTING: University hospital. MEASUREMENTS: The probability
      of each of 66,561 cases taking longer than scheduled was estimated with an
      accuracy to within 1-2%. MAIN RESULTS: Overall underestimation by surgeons and
      schedulers was 22 minutes for each 8 hours of used operating room (OR) time. If a
      90% or 95% chance of taking longer than scheduled were required to conclude that
      a case's duration was deliberately underestimated, and if such cases' scheduled
      durations were changed, overall underestimation would be reduced by only 0.2 or
      0.9 minutes per 8 hours of used OR time because only 0.1% or 0.6% of used OR time
      met that criterion. In contrast, underestimation would be reduced by 20 minutes
      if the cases identified were those with only a 50% to 60% chance of taking longer
      than scheduled because they accounted for more than 40% of OR time. Persistent
      underestimation of cases' durations was caused not by poor decisions for a few
      outlier cases, but instead by slight underestimation for many cases. Surgeons'
      and schedulers' behavior that fit cases into staffed (allocated) OR time was to
      underestimate slightly the duration of many cases. CONCLUSION: The impact of
      inaccurate, scheduled case duration on staffing costs and unpredictable work
      hours can be reduced by allocating appropriate total hours of OR time (ie,
      staffing) for the cases that will get done, regardless of the inaccuracy of the
      scheduled durations of those cases.

PMID- 17531729
TI  - Caudal epidural anesthesia administered intraoperatively provides for effective
      postoperative analgesia after total hip arthroplasty.
AB  - STUDY OBJECTIVE: To investigate the use of caudal epidural anesthesia for
      postoperative pain after total hip arthroplasty. DESIGN: Prospective study.
      SETTING: University-affiliated hospital. PATIENTS: 32 (4 men and 28 women)
      patients, aged 49 to 89 years, scheduled for total hip arthroplasty for
      osteoarthritis of the hip. INTERVENTIONS AND MEASUREMENTS: Patients were
      allocated to three groups: lumbar epidural anesthesia (EA group; n = 16) or
      caudal epidural anesthesia (CA group; n = 16) groups, which were case-matched
      according to patient demographics. Nine patients received general anesthesia only
      (GA group). We evaluated the level of postoperative pain using a 100-mm Visual
      Analog Scale (VAS) recorded at 3, 6, 9, 12, and 24 hours after surgery. MAIN
      RESULTS: Total requirement of diclofenac sodium suppositories was significantly
      larger in the GA group than in the EA or CA groups (444 +/- 302 vs 188 +/- 124
      and 145 +/- 130 mg). The number of days requiring analgesics was significantly
      prolonged in the GA group compared with the EA or CA groups (14 +/- 9 vs 4 +/- 3
      and 4 +/- 4 days). These items were similar between the EA group and the CA
      group. All VAS values for pain, rest, and movement in the postsurgical period
      over 24 hours were significantly higher in the GA group than in either the EA or
      CA groups. CONCLUSIONS: Caudal epidural anesthesia provides effective
      postoperative analgesia similar to lumbar epidural anesthesia.

PMID- 17531730
TI  - Ulnar artery versus radial artery approach for arterial cannulation: a
      prospective, comparative study.
AB  - STUDY OBJECTIVE: To compare the ease of cannulation, success/failure rate, and
      complication rate between ulnar and radial arteries. DESIGN: Randomized,
      controlled study. SETTING: Operating room. PATIENTS: 100 ASA physical status I,
      II, and III patients undergoing general anesthesia and requiring arterial
      cannulation. INTERVENTIONS: Patients were divided randomly into two separate
      groups of 50 patients each according to cannulation site: ulnar artery (group U)
      or radial artery (group R) group. MEASUREMENTS: The presence and fullness of the
      arterial pulses (strong/weak/absent), ease of cannulation (cases in which
      cannulation was successful on the first attempt and those that which required
      more than one cannulation attempt), success rate of cannulation, and
      complications (early/late) were all recorded. MAIN RESULTS: The radial artery was
      stronger in pulse (83% vs 73%). The success rates of cannulations for the ulnar
      and radial arteries were 82% and 90%, respectively (P > 0.05). The overall
      success rate of cannulation in the ulnar group with a strong pulse was 100%.
      There were significant differences in the success rate of cannulation between the
      patients with strong and weak pulses in the ulnar group (P < 0.0001). Ease of
      cannulation and complication rates of cannulations were not statistically
      different in both groups. CONCLUSIONS: The success rate of an arterial
      cannulation in a patient with a strong ulnar pulse is the same as for radial
      artery cannulation.

PMID- 17531731
TI  - Efficacy of ropivacaine, bupivacaine, and levobupivacaine for labor epidural
      analgesia.
AB  - STUDY OBJECTIVE: To compare analgesic efficacy and intensity of motor block with
      continuous infusions of ropivacaine, bupivacaine, and levobupivacaine in
      combination with fentanyl for labor epidural analgesia. DESIGN: Prospective,
      randomized, double-blinded study. SETTING: Labor and delivery suite at Magee
      Womens Hospital, Pittsburgh, PA. PATIENTS: 162 ASA physical status I and II, full
      term, primiparous women. INTERVENTIONS: All patients received epidural labor
      analgesia. Epidural medication consisted of an initial bolus of 8 mL local
      anesthetic with fentanyl (100 microg) followed by an infusion at 12 mL/h of local
      anesthetic with 2 microg/mL fentanyl. Patients were allocated to one of three
      groups, as follows: group 1 received bolus and infusion of bupivacaine 0.125%,
      group 2 received bolus and infusion of levobupivacaine 0.125%, and group 3
      received a bolus of ropivacaine 0.2% and infusion of ropivacaine 0.1%.
      MEASUREMENTS: Maternal vital signs, pain visual analog scale (VAS) score, sensory
      levels, and motor block (Bromage score) were recorded every hour. Duration of
      first and second stage of labor and mode of delivery were also recorded. RESULTS:
      There were no statistically significant differences in pain VAS or Bromage motor
      scores among the three groups of patients at any of the measured time intervals.
      The time to achieve T10 sensory level and patient comfort was shorter in the
      ropivacaine (9.35 +/- 4.96 min) and levobupivacaine (9.56 +/- 4.71 min) groups
      than the bupivacaine (11.89 +/- 7.76 min) group, although this difference did not
      reach a statistically significant level (P = 0.06). The second stage was
      significantly shorter in the bupivacaine group, lasting 81.27 +/- 63.3 min,
      compared with the ropivacaine group (121.69 +/- 86.5 min) and the levobupivacaine
      (115.5 +/- 83.6 minutes) group (P = 0.04). CONCLUSION: There are no significant
      differences in pain VAS and Bromage scores between 0.1% ropivacaine, 0.125%
      bupivacaine, and 0.1% levobupivacaine given for labor epidural analgesia.

PMID- 17531732
TI  - Difficult airway management after carotid endarterectomy: utility and limitations
      of the Laryngeal Mask Airway.
AB  - This case series details successful management of life-threatening airway
      obstruction after carotid endarterectomy. In the first case, ventilation was
      restored with a Laryngeal Mask Airway. In the second case, laryngeal mask airway
      rescue was unsuccessful, necessitating percutaneous transtracheal jet ventilation
      and subsequent endotracheal intubation with direct laryngoscopy.

PMID- 17531733
TI  - Anesthesia for pancreatoduodenectomy in a patient with history of coronary artery
      bypass graft surgery: determination of optimal surgical management by the graft
      clamping test.
AB  - We report a case of a 72-year-old man undergoing pancreatoduodenectomy, who had a
      history of coronary artery bypass graft surgery using the right gastroepiploic
      artery. We intraoperatively used the graft clamping test, which was assessed via
      electrocardiography and transesophageal echocardiography, to verify patency of
      the right gastroepiploic artery graft. Because the graft clamping test was
      positive, first, we interposed the saphenous vein graft between the splenic
      artery and right coronary artery. The abdominal surgery was then successfully
      performed without any cardiac complications. In such a complicated case,
      anesthesiologists who are responsible for assessment of the graft clamping test
      play a crucial role in determining the optimal surgical procedure.

PMID- 17531734
TI  - The efficacy of postoperative perineural infusion of bupivacaine and clonidine
      after lower extremity amputation in preventing phantom limb and stump pain.
AB  - We report the efficacy of perioperative infusion of clonidine and bupivacaine for
      above-knee amputation in a patient with a history of phantom limb pain in the
      same extremity after a previous below-knee amputation. The patient underwent
      general anesthesia. Before transection, the sciatic nerve was infiltrated with
      0.25% bupivacaine 5 mL and clonidine 50 microg. After the nerve was severed, a 20
      gauge epidural catheter was inserted into the nerve sheath and externalized
      laterally through a separate skin incision. Before closure, 0.25% bupivacaine 10
      mL and clonidine 50 microg was injected, and 0.1% bupivacaine and clonidine two
      microg/mL was infused at 10 mL/h for the first 96 hours postoperatively. There
      were no incidents of hypotension, bradycardia, or sedation during the infusion
      period. The mean postoperative pain score (from 0 to 10) for 96 hours was 1.2 +/-
      0.7. The patient required a total of 10 mg of oxycodone postoperatively. The
      patient did not report either stump or phantom pain for 12 months after surgery.

PMID- 17531735
TI  - Neuraxial anesthesia for cesarean delivery in a parturient with type 1 von
      Willebrand disease and scoliosis.
AB  - We present the case of a parturient with von Willebrand disease and scoliosis who
      required cesarean delivery. Neuraxial anesthesia was used for the patient. The
      indications for neuraxial anesthesia with regard to type 1 von Willebrand disease
      are reviewed.

PMID- 17531736
TI  - Bilateral bronchial intubation through a tracheostomy incision after innominate
      artery laceration.
AB  - A 17-year-old adolescent boy presented for direct laryngoscopy, rigid
      bronchoscopy, laser ablation of tracheal scar, and possible tracheostomy. The
      innominate artery was lacerated during tracheostomy. We describe a unique
      approach toward ventilation in this case in which two separate endotracheal tubes
      were connected through a Carlens tube adaptor.

PMID- 17531737
TI  - Two cases of idiopathic superior laryngeal neuralgia treated by superior
      laryngeal nerve block with a high concentration of lidocaine.
AB  - Carbamazepine therapy is among the most effective drug regimens to treat patients
      who have superior laryngeal neuralgia similar to trigeminal neuralgia. However,
      some patients are resistant to carbamazepine. We report two patients with
      superior laryngeal neuralgia who were successfully treated with superior
      laryngeal block using high concentrations of lidocaine, after treatment with
      carbamazepine failed.

PMID- 17531738
TI  - Long-acting local anesthetics at home: do we need to worry?

PMID- 17531739
TI  - The Airway Scope for difficult intubation.

PMID- 17531741
TI  - Teaching ultrasound-guided interscalene blocks: description of a simple and
      effective technique.

PMID- 17531742
TI  - Optimising treatment decisions for the onco-geriatric patient: the need for
      Comprehensive Geriatric Assessment in routine clinical practice.

PMID- 17531743
TI  - Pre-operative assessment of cancer in the elderly (PACE): a comprehensive
      assessment of underlying characteristics of elderly cancer patients prior to
      elective surgery.
AB  - BACKGROUND: Cancer is a disease that particularly affects the elderly and,
      although surgery is the first treatment choice, many elderly cancer patients do
      not receive standard surgery because they are considered unfit for treatment due
      to an inaccurate estimation of operative risk. Pre-operative Assessment of Cancer
      in the Elderly (PACE) was developed in order to address the need to provide
      detailed information about the functional reserve of the elderly cancer patient
      to aid individualised management. METHODS: PACE incorporates a battery of
      validated instruments including the Comprehensive Geriatric Assessment (CGA),
      Brief Fatigue Inventory (BFI), Eastern Cooperative Oncology Group Performance
      Status (ECOG-PS), and American Society Anesthesiologists (ASA) grade. An
      international prospective study was conducted with 460 consecutive elderly cancer
      patients (216 breast, 146 GIT, 71 GUT, 27 other) receiving PACE prior to
      receiving elective surgery. RESULTS: Three hundred and eighty four patients
      (83.4%) were observed to have at least one co-morbidity; the most common being
      hypertension (n=246, 53.5%). More than two thirds of the patients had good
      functional and mental status according to PACE. After adjusting for age, sex and
      type of cancer, six of the seven items of PACE were found to be significantly
      associated with co-morbidities (according to the Satariano's Index of Co
      morbidities (SIC)). A multivariate analysis identified IADL, BFI and ASA to be
      the most important instruments in explaining SIC. DISCUSSION: PACE has been
      effectively used to describe the functional capacity and health status in an
      international cohort of elderly cancer patients. The majority of PACE instruments
      have been found to be significantly associated with co-morbidities (SIC) and can
      distinguish between type and severity of cancer. PACE represents a useful tool in
      evaluating onco-geriatric fitness for surgery.

PMID- 17531744
TI  - Applied vascular anatomy of the colon and rectum: clinical implications for the
      surgical oncologist.
AB  - Surgery remains the most radical method of treatment of many solid tumors,
      including colorectal cancer; in these tumors, surgery is the only method that can
      offer the chance of cure. To avoid early postoperative morbidity (mainly,
      anastomotic leak) and to achieve good long-term results (low incidence of tumor
      recurrence, long overall and disease-free survival, and optimal quality of life),
      the surgeon should have an in-depth knowledge of vascular anatomy of the colon
      and rectum. This essential requirement is based on the fact that the actual
      course followed by lymph fluid drainage from any part of the colon/rectum is
      determined by its blood supply; therefore, the extent of resection for colorectal
      cancer follows the principles of blood supply and lymphatic drainage. Knowledge
      of the colorectal vascular anatomy and its variations is of vital importance in
      the planning of radical surgical treatment and in appropriately performing
      colorectal resections, particularly in the patient who underwent in the past
      colectomy or aortic surgery that has changed the usual pattern of collateral
      blood supply to the colon. This review summarizes currently available data
      regarding vascular anatomy of the colon and rectum, from a surgical perspective.

PMID- 17531746
TI  - Ensuring sexual and reproductive health for people living with HIV: an overview
      of key human rights, policy and health systems issues.
AB  - Despite rhetorical attention there is little programmatic guidance as to how best
      to ensure that women and men living with HIV have access to sexual and
      reproductive health services that help them realise their reproductive goals,
      while ensuring their human rights. A dynamic relationship exists between the
      manner in which health services and programmes are delivered, and the individuals
      who seek these services. A review of the literature shows clear gaps and
      highlights areas of concern not yet sufficiently addressed. The delivery and use
      of health services and programmes is shaped by the underlying determinants of
      people's access to and use of these services, the health systems in place at
      community and country level, and the legal and policy environment these systems
      operate in. Few governments can provide the full range of services that might be
      required by their populations. In most places, people access health services from
      a variety of formal and informal providers, and health-related behaviour is
      influenced from many directions. The synergistic roles of health systems, law and
      policy and underlying social determinants in helping or hindering the development
      and delivery of adequate programmes and services for HIV positive people must be
      addressed.

PMID- 17531747
TI  - Rights of HIV positive people to sexual and reproductive health: parenthood.
AB  - In many areas of the globe most HIV infection is transmitted sexually or in
      association with pregnancy, childbirth and breastfeeding, raising the need for
      sexual and reproductive health and HIV/AIDS initiatives to be mutually
      reinforcing. Many people with HIV, who are in good health, will want to have
      children, and highly active antiretroviral therapy provides women and men living
      with AIDS the possibility of envisaging new life projects such as parenthood,
      because of a return to health. However, there are still difficult choices to face
      concerning sexuality, parenthood desires and family life. Structural, social and
      cultural issues, as well as the lack of programmatic support, hinder the
      fulfilment of the right to quality sexual and reproductive health care and
      support for having a family. This paper addresses the continuum of care involved
      in parenthood for people living with HIV, from pregnancy to infant and child
      care, and provides evidence-based examples of policies and programmes that
      integrate sexual and reproductive health interventions with HIV/AIDS care in
      order to support parenthood. Focusing on parenthood for people living with and
      affected by HIV, that is, focusing on the couple rather than the woman as the
      unit of care, the individual or the set of adults who are responsible for raising
      children, would be an innovative programmatic advance. Going beyond maternal and
      child health care to providing care and support for parents and others who are
      responsible for raising children is especially relevant for those living with HIV
      infection.

PMID- 17531748
TI  - Reproductive choice for women and men living with HIV: contraception, abortion
      and fertility.
AB  - From a policy and programmatic point of view, this paper reviews the literature
      on the fertility-related needs of women and men living with HIV and how the entry
      points represented by family planning, sexually transmitted infection and HIV
      related services can ensure access to contraception, abortion and fertility
      services for women and men living with HIV. Most contraceptive methods are safe
      and effective for HIV positive women and men. The existing range of contraceptive
      options should be available to people living with HIV, along with more
      information about and access to emergency contraception. Potential drug
      interaction must be considered between hormonal contraception and treatment for
      tuberculosis and certain antiretroviral drugs. Couples living with HIV who wish
      to use a permanent contraceptive method should have access to female
      sterilisation and vasectomy in an informed manner, free of coercion. How to
      promote condoms and dual protection and how to make them acceptable in long term
      relationships remains a challenge. Both surgical and medical abortion are safe
      for women living with HIV. To reduce risk of vertical transmission of HIV and in
      cases of infertility, people with HIV should have access to sperm washing and
      other assisted conception methods, if these are available. Simple and cost
      effective procedures to reduce risk of vertical transmission should be part of
      counselling for women and men living with HIV who intend to have children.
      Support for the reproductive rights of people with HIV is a priority. More
      operations research on best practices is needed.

PMID- 17531749
TI  - Sexual health for people living with HIV.
AB  - Sexual health is defined in terms of well-being, but is challenged by the social,
      cultural and economic realities faced by women and men with HIV. A sexual rights
      approach puts women and men with HIV in charge of their sexual health. Accurate,
      accessible information to make informed choices and safe, pleasurable sexual
      relationships possible is best delivered through peer education and health
      professionals trained in empathetic approaches to sensitive issues. Young people
      with HIV especially need appropriate sex education and support for dealing with
      sexuality and self-identity with HIV. Women and men with HIV need condoms,
      appropriate services for sexually transmitted infections, sexual dysfunction and
      management of cervical and anogenital cancers. Interventions based on positive
      prevention, that combine protection of personal health with avoiding HIV/STI
      transmission to partners, are recommended. HIV counselling following a positive
      test has increased condom use and decreased coercive sex and outside sexual
      contacts among discordant couples. HIV treatment and care have reduced stigma and
      increased uptake of HIV testing and disclosure of positive status to partners.
      High adherence to antiretroviral therapy and safer sexual behaviour must go hand
      in-hand. Sexual health services have worked with peer educators and volunteer
      groups to reach those at higher risk, such as sex workers. Technological advances
      in diagnosis of STIs, microbicide development and screening and vaccination for
      human papillomavirus must be available in developing countries and for those with
      the highest need globally.

PMID- 17531750
TI  - Meeting the sexual and reproductive health needs of people living with HIV:
      challenges for health care providers.
AB  - A trained health service workforce is critical to ensuring good quality service
      delivery to people with HIV. There is only limited documented information on the
      challenges and constraints facing health care providers in meeting the sexual and
      reproductive health needs of HIV positive women and men. This paper reviews
      information on providers' attitudes, motivation and level of preparedness in
      addressing the sexual and reproductive health needs of people living with HIV in
      the context of the human resources crisis and emerging treatment and prevention
      strategies. There is a need for significant investment in improving the health
      infrastructure and providers' ability to take universal precautions against
      infection in health care settings. Additionally, there is need for comprehensive
      and appropriate training for health care providers to build their capacity to
      meet the requirements and expectations of different sub-populations of HIV
      positive people. This includes not only physicians but also nurses and midwives,
      who are the primary caregivers for most of the population in many resource-poor
      settings. Supportive and knowledgeable providers are crucial for helping HIV
      positive people seek and adhere to treatment, prevent sexually transmitted
      infections, unintended pregnancies and vertical transmission of HIV and support
      positive living free from stigma and discrimination. Providers, some of whom may
      themselves be HIV positive, can make an important difference, especially if they
      are supported in their working conditions, are knowledgeable about HIV and sexual
      and reproductive health and have the skills to provide good quality care.

PMID- 17531751
TI  - Sexual and reproductive health services and HIV testing: perspectives and
      experiences of women and men living with HIV and AIDS.
AB  - All over the world HIV has been stigmatised, making it difficult for people
      living with HIV to access testing, treatment, care and counselling or even to act
      on a diagnosis or get advice and treatment, for fear of being judged. Prejudice
      in society has also often been reflected and reproduced by health care providers.
      A human rights approach, which positively incorporates sexual and reproductive
      rights, rather than a restricted medical view, is therefore essential for the
      achievement of true partnerships between health care providers and service users.
      This paper is about the experiences of HIV positive women and men in sexual and
      reproductive health services and HIV testing. It provides guidance not only on
      how things could and should be done but also on how they should not be done. It
      outlines the sexual and reproductive rights positive people consider crucial and
      gives examples of how these are being violated. It presents perceptions and
      implications of HIV testing and how health services can support people after a
      positive diagnosis. It analyses the importance of confidentiality, continuity of
      care, knowledge and information, and the role of support groups and home-based
      care. It calls on sexual and reproductive health services to address issues of
      stigma and discrimination when offering and carrying out HIV testing and
      counselling, and in providing treatment, care and support.

PMID- 17531753
TI  - Challenges and prospects for community-partnered research.

PMID- 17531754
TI  - Partnership selection and formation: a case study of developing adolescent health
      community-researcher partnerships in fifteen U.S. communities.
AB  - PURPOSE: This study describes the partner selection process in 15 U.S.
      communities developing community-researcher partnerships for the Connect to
      Protect (C2P): Partnerships for Youth Prevention Interventions, an initiative of
      the Adolescent Trials Network for human immunodeficiency virus/acquired immune
      deficiency syndrome (HIV/AIDS) Interventions. METHODS: Each site generated an
      epidemiological profile of urban youth in their community, selected a focus
      population and geographic area of youth at risk for HIV, conducted a series of
      successive structured interviews, and engaged in a process of relationship
      building efforts culminating in a collaborative network of community agencies.
      RESULTS: Sites chose as their primary target population young women who have sex
      with men (n = 8 sites), young men who have sex with men (n = 6), and intravenous
      drug users (n = 1). Of 1162 agencies initially interviewed, 281 of 335 approached
      (84%) agreed to join the partnership (average 19/site). A diverse array of
      community agencies were represented in the final collaborative network; specific
      characteristics included: 93% served the sites' target population, 54% were
      predominantly youth oriented, 59% were located in the geographical area of focus,
      and 39% reported provision of HIV/STI (sexually transmitted infection) prevention
      services. Relationship-building activities, development of collaborative
      relationships, and lessons learned, including barriers and facilitators to
      partnership, are also described. CONCLUSIONS: Study findings address a major gap
      in the community partner research literature. Health researchers and policymakers
      need an effective partner selection framework whereby community-researcher
      partnerships can develop a solid foundation to address public health concerns.

PMID- 17531755
TI  - Youth United Through Health Education: community-level, peer-led outreach to
      increase awareness and improve noninvasive sexually transmitted infection
      screening in urban African American youth.
AB  - PURPOSE: To evaluate the effectiveness of the Youth United Through Health
      Education (YUTHE) program, a community-level, peer-led outreach program to
      increase awareness and improve noninvasive sexually transmitted infection (STI)
      screening in youth residing in the targeted community. METHODS: Sexually
      experienced youth, aged 12-22 years, anonymously participated in the YUTHE
      program (a 15-minute encounter, including a risk assessment with feedback and
      prevention messages). A street- and venue-based intercept approach using a
      nonequivalent control group design was implemented to evaluate the YUTHE program.
      RESULTS: YUTHE community respondents were more likely to know that STIs could be
      asymptomatic (odds ratios [OR] 1.36, 95% confidence interval [CI] 1.08-1.72),
      know about urine-based STI screening tests (OR 1.34, 95% CI 1.04-1.72), perceive
      themselves to be at risk for STIs (OR 1.71, 95% CI 1.11-2.62), and worried about
      acquiring an STI (OR 1.50, 95% CI 1.04-2.18). No other community differences were
      identified. However, respondents who reported a single contact (OR = 2.12, 95% CI
      = 1.11-4.03) or multiple contacts (OR 2.78, 95% CI 1.81-4.26) with the YUTHE
      program were more likely to have been tested for STIs in the previous six months.
      CONCLUSIONS: We did not accomplish our overall goal of increasing STI screening
      in our outreach community relative to the comparison community; our findings
      suggest that a peer-led, street- and venue-based community outreach approach is a
      feasible means for reaching large numbers of adolescents for STI prevention.

PMID- 17531756
TI  - Aggregating indices of risk and protection for adolescent behavior problems: the
      Communities That Care Youth Survey.
AB  - PURPOSE: To facilitate research on adolescent risk and protection regarding
      behavior problems, and to facilitate community decision-making regarding resource
      allocation for intervention programs, by creating a reduced set of coherent
      aggregate indices of adolescent risk and protection. METHODS: We examined the 31
      risk and protective factor scales in the Communities That Care Youth Survey (CTC
      YS). Data came from two waves of the CTC-YS administered to sixth through 12th
      graders in Pennsylvania (2001 n = 43,842; 2003 n =101,988). Factor analysis and
      calculation of internal reliability were used to create aggregate indices of
      risk/protective factor domains. Correlations of aggregate indices with each other
      and with problem behaviors (antisocial behavior, substance use) were examined.
      RESULTS: Theory and empirical results led to the creation of seven coherent
      indices: Community Cohesion, Family Cohesion, Family Risk, School Support for
      Prosocial Activities, Antisocial Peer Domain, Attitudes toward Risky Behavior,
      Risky Behavioral Tendencies. Four scales were not included in the aggregate index
      (Religiosity, Academic Performance, Personal Transitions and Mobility, and Early
      Initiation of Drug Use and Antisocial Behavior). The indices were related to each
      other and to adolescent problem behaviors (antisocial behavior and substance use)
      in expected ways. Results were consistent across waves of data. CONCLUSIONS: The
      construction of theoretically meaningful and empirically defensible aggregate
      measures of adolescent risk and protective factors is possible, although analyses
      of other data sets and further discussion are warranted. The use of aggregate
      indices by researchers and communities is recommended as a way to facilitate
      research and decision-making.

PMID- 17531757
TI  - Challenges in replicating interventions.
AB  - PURPOSE: To describe and reflect on an effort to document, through a set of 6
      interventions, the process of adapting effective youth risk behavior
      interventions for new settings, and to provide insights into how this might best
      be accomplished. METHODS: Six studies were funded by the NIH, starting in 1999.
      The studies were funded in response to a Request for Applications (RFA) to
      replicate HIV prevention interventions for youth. Researchers were to select an
      HIV risk reduction intervention program shown to be effective in one adolescent
      population and to replicate it in a new community or different adolescent
      population. This was to be done while systematically documenting those processes
      and aspects of the intervention hypothesized to be critical to the development of
      community-based, culturally sensitive programs. The replication was to assess the
      variations necessary to gain cooperation, implement a locally feasible and
      meaningful intervention, and evaluate the outcomes in the new setting. The
      rationale for this initiative and description of the goals and approaches to
      adaptation of the funded researchers are described. RESULTS: Issues relevant to
      all interventions are discussed, in addition to those unique to replication. The
      processes and the consequences of the adaptations are then discussed. The further
      challenges in taking a successful intervention "to scale" are not discussed.
      CONCLUSIONS: Replications of effective interventions face all of the challenges
      of implementation design, plus additional challenges of balancing fidelity to the
      original intervention and sensitivity to the needs of new populations.

PMID- 17531758
TI  - Body mass index and the prevalence of metabolic syndrome among children and
      adolescents in two Mexican populations.
AB  - PURPOSE: To report the prevalence of metabolic syndrome (MS) among children and
      adolescents living in central Mexico, and its association with body mass index
      (BMI). METHODS: In a sample of 1366 subjects from 7 to 24-years-old, a self
      administered questionnaire was used to determined demographic characteristics.
      The definition of pediatric MS was determined using analogous criteria to Adult
      Treatment Panel III (ATPIII) as > or = 3 of the following: concentration of
      triglycerides > or = 100 mg/dL, HDL cholesterol < 45 mg/dL for males and < 50
      mg/dL for females, waist circumference > or = 75th percentile (sex specific),
      glucose concentration > or = 110 to < 126 mg/dL, and systolic or diastolic blood
      pressure > or = 90th percentile (age, height, and sex specific). RESULTS: Most of
      the sample was in the 10-14- (32.4%) and the 15-19-year (35.4%) age groups,
      mostly females (57%), and 31% of this young sample was overweight (mean BMI =
      21.6 kg/m2). About 1 in every 5 participants had full criteria for MS (19.2%, 95%
      confidence interval [CI]: 16.4-22.1 among females, and 20.2%, 95% CI: 17.1-23.7
      among males), and only 1 in every 10 was free of any MS component. The most
      common component was a low HDL level, observed in 85.4% of the sample.
      Unfavorable fat distribution, as indicated by a large waist circumference, was
      present in 27.9% of the sample. About 66% of those 10-14-year-olds with a large
      BMI were positive for MS. CONCLUSIONS: MS and overweight are major problems for
      youth in Mexico. Immediate and comprehensive actions at home and schools are
      needed if Mexico wants to avoid the heavy burden that this disorder will have for
      its population in the near future.

PMID- 17531759
TI  - Early adolescent exposure to alcohol advertising and its relationship to underage
      drinking.
AB  - PURPOSE: To determine whether early adolescents who are exposed to alcohol
      marketing are subsequently more likely to drink. Recent studies suggest that
      exposure to alcohol ads has a limited influence on drinking in mid-adolescence.
      Early adolescents may be more vulnerable to alcohol advertising effects. METHODS:
      Two in-school surveys of 1786 South Dakota youth measured exposure to television
      beer advertisements, alcohol ads in magazines, in-store beer displays and beer
      concessions, radio-listening time, and ownership of beer promotional items during
      6th grade, and drinking intentions and behavior at 7th grade. Multivariate
      regression equations predicted the two drinking outcomes using the advertising
      exposure variables and controlling for psychosocial factors and prior drinking.
      RESULTS: After adjusting for covariates, the joint effect of exposure to
      advertising from all six sources at grade 6 was strongly predictive of grade 7
      drinking and grade 7 intentions to drink. Youth in the 75th percentile of alcohol
      marketing exposure had a predicted probability of drinking that was 50% greater
      than that of youth in the 25th percentile. CONCLUSIONS: Although causal effects
      are uncertain, policy makers should consider limiting a variety of marketing
      practices that could contribute to drinking in early adolescence.

PMID- 17531760
TI  - Factors affecting abortion decisions among young couples in Nepal.
AB  - PURPOSE: To explore, using both survey data and case studies, factors that are
      associated with abortion decisions among young couples in the context of recently
      legalized abortion in Nepal. METHODS: This article draws primarily on data
      collected in detailed case histories of 30 participants selected from a sample of
      the respondents to a survey of 997 married women aged 15 to 24 years and 499 men
      aged 15 to 27 years collected in 2003. Bivariate analyses of the survey data are
      presented in summary form to provide some general contextual background, with the
      key themes that emerged from analysis of the case histories being described.
      RESULTS: Almost half of the young women in the survey reported that they had ever
      experienced an unintended pregnancy. A considerable proportion of these couples
      thought about abortion but the majority of them did not take any action. Some of
      them had attempted abortion but only few had succeeded. Multiple factors,
      including socio-cultural beliefs, affect the decision-making phase, making the
      process dynamic and situation-specific. Husbands and health service providers
      play a major role in the decision-making process. CONCLUSIONS: The study
      highlights the need to scale up family planning and abortion services to young
      couples, and emphasizes the importance of involving men and service providers in
      public education and advocacy campaigns against unsafe abortion. It also points
      to the need for wider education in the community about family planning and legal
      abortion services, as well as for the transparent pricing of services and greater
      efforts to enhance women's decision-making capacities and control over their
      reproductive options.

PMID- 17531761
TI  - Acculturation and parent-adolescent communication about sex in Filipino-American
      families: a community-based participatory research study.
AB  - PURPOSE: To examine whether acculturation is associated with parent-adolescent
      communication about sex in Filipino-American families. Filipino-Americans, the
      United States' second-largest Asian and Pacific Islander (API) group, have more
      adolescent pregnancy and HIV infection than other APIs. High-quality parent
      adolescent communication about sex has been associated with healthy sexual
      development, and acculturation has been associated with various increased health
      risks. Whether acculturation affects parent-adolescent communication is unknown.
      METHODS: We surveyed 120 pairs of Filipino-American parents and adolescents at a
      single large high school. We asked adolescents about their frequency of parent
      adolescent communication about sex and measured adolescent acculturation in two
      ways: disagreement with traditional Asian values and preferential use of English.
      In bivariate and multivariate regressions, we examined whether adolescent
      acculturation was associated with adolescent reports of parent-adolescent
      communication. RESULTS: Few adolescents (22%) reported regularly discussing sex
      with parents. Although most adolescents (72%) agreed with traditional Asian
      values, most (63%) preferred using English. In bivariate regressions, less parent
      adolescent communication about sex was associated with less adolescent agreement
      with traditional Asian values (p = .002) and more adolescent English use (p =
      .009). In multivariate regressions, these associations were largely explained by
      adolescent perceptions of parent knowledge about their whereabouts and
      activities. CONCLUSIONS: Acculturation may influence Filipino-American parent
      adolescent communication about sex and, consequently, Filipino-American
      adolescent sexual health. Health care and public health providers may need to
      tailor adolescent sexual health programs based on acculturation or other
      immigration-related factors.

PMID- 17531762
TI  - The effect of childhood physical and sexual abuse on adolescent weapon carrying.
AB  - PURPOSE: To examine the link and explore a potential association between physical
      and sexual abuse and weapon carrying in a sample of youth. Weapon carrying has
      been linked to the perpetration of serious violence in youth. Ample evidence
      associates child maltreatment with the perpetration of delinquent and violent
      behavior, but there is little research on the relationship between child
      maltreatment and weapon carrying. METHODS: We analyzed cross-sectional data
      collected from students in a large survey of high-risk youth (n = 3487).
      Propensity score stratification was used to approximate a randomized experimental
      design to examine the effect of physical and sexual abuse on youth-reported
      weapon and firearm carrying. RESULTS: Approximately 25% of weapon carrying by
      girls was attributable to sexual abuse in early childhood. We found no
      relationship between sexual abuse and weapon carrying for boys. The association
      between physical abuse and weapon carrying was less robust and no gender
      difference was detected. CONCLUSIONS: Results indicate that exposure to certain
      forms of early childhood maltreatment may increase the probability of weapon
      carrying in adolescence, particularly for females. Sexual abuse prevention and
      intervention programs should incorporate personal safety alternatives to weapon
      carrying, and clinicians should be aware that sexually abused girls are at
      greater risk for weapon carrying than other maltreated youth.

PMID- 17531763
TI  - Attitudes of mothers in Da Nang, Vietnam toward a human papillomavirus vaccine.
AB  - PURPOSE: To describe attitudes and acceptability toward a human papillomavirus
      (HPV) vaccine among mothers in Da Nang, Vietnam and examine factors that may
      influence HPV vaccine uptake. METHODS: Women who were the primary caregiver of a
      girl 10-18 years old ("mothers") were eligible to participate. Mothers were
      recruited face-to-face from Da Nang General Hospital. Participants completed a
      survey addressing general vaccine attitudes, attitudes toward an HPV vaccine,
      beliefs about sexuality, recommendations from others, and likelihood of having
      their daughter vaccinated against HPV. A total of 194 surveys were returned; 181
      (93%) contained analyzable data. RESULTS: Eleven percent of mothers were aware of
      an HPV vaccine. Ninety-four percent believed that the HPV vaccine will be
      effective and 90% disagreed that their daughter would have sex early if she was
      vaccinated. Beliefs regarding premarital sex, such as "girls who have sex before
      marriage are not respected" and "it would be hard to find a husband" were held by
      76% and 62% of mothers, respectively. Despite this, over 90% were in favor of
      their daughter receiving the HPV vaccine. Ninety-five percent indicated that a
      recommendation from their doctor would be very important in their decision
      making, and 78% indicated that the media would be very important. CONCLUSIONS:
      Initial responses to the HPV vaccine for girls in Vietnam appear favorable.
      Beliefs regarding negative social consequences for girls who engage in premarital
      sex are prevalent but unassociated with HPV vaccine acceptability. Accurate and
      consistent recommendations from doctors and media sources will be important for
      vaccination efforts.

PMID- 17531764
TI  - Immunization of early adolescent females with human papillomavirus type 16 and 18
      L1 virus-like particle vaccine containing AS04 adjuvant.
AB  - PURPOSE: In female individuals 15-25-years of age, the AS04-containing human
      papillomavirus (HPV)-16/18 vaccine is highly immunogenic and provides up to 100%
      protection against HPV-16/18 persistent infection and associated cervical lesions
      up to 4.5 years. Optimal cervical cancer prevention will require prophylactic
      vaccination against oncogenic HPV 16 and 18 before the onset of sexual activity
      in early adolescent girls. To establish the feasibility of vaccination in girls
      10-14 years of age, we compared the immunogenicity and safety in early adolescent
      female individuals to those 15-25 years in whom vaccine efficacy has been
      demonstrated. METHODS: We enrolled 773 female participants aged 10-14 years and
      15-25 years to receive the HPV-16/18 L1 VLP AS04 vaccine, which was administered
      at months 0, 1, and 6. Serum samples were collected at months 0 and 7; antibodies
      to HPV 16 and 18 VLPs were measured by enzyme-linked immunosorbent assay. Vaccine
      safety was assessed at 7 or 30 days after each dose; serious adverse events were
      recorded during the entire study period. RESULTS: Both age groups achieved 100%
      seroconversion for HPV 16 and 18. Participants in the group aged 10-14 years were
      not only noninferior to those 15-25 years in terms of HPV 16 and 18
      seroconversion rates but also had approximately twice as high geometric mean
      titers. The vaccine was generally safe and well tolerated. CONCLUSIONS: These
      findings suggest that HPV vaccination during early adolescence is generally safe,
      well tolerated, and highly immunogenic. The observed higher antibody titers in
      the group 10-14 years of age are likely to result in longer antibody persistence.
      Overall, these data support the implementation of prophylactic HPV vaccination in
      this age group.

PMID- 17531765
TI  - Break the silence: HIV/AIDS knowledge, attitudes, and educational needs among
      Arab university students in United Arab Emirates.
AB  - PURPOSE: In light of increasing spread of human immunodeficiency virus (HIV) in
      the Middle East, we assessed knowledge, attitudes, and educational needs of young
      people in United Arab Emirates (UAE), a modern and moderately conservative
      Islamic country. METHODS: A cross-sectional survey among randomly selected first
      year, gender-segregated Arab students at the national university in Al Ain in
      2005 was conducted using an adaptation of an anonymous self-administered World
      Health Organization questionnaire. Knowledge and attitudes were scored. RESULTS:
      Response was 89%; 119 males and 148 females. Knowledge scores about HIV/AIDS were
      low for 75%, moderate for 24%, high for <1%. Although 90% knew main routes of
      infection, there were misconceptions about transmission, and only 31% knew there
      is no vaccine and 34% no cure. Religion was stated as a reason to avoid
      extramarital relationships by 91% and sexually transmitted diseases (STDs) by
      38%; 94% favored premarital testing. Attitudes toward people living with HIV
      (PLH) were neither friendly nor tolerant, including 97% who felt all people
      entering UAE should be tested, 53% that PLH should be forced to live apart, and
      only 27% who felt children with HIV should be allowed to attend school. Ninety
      six percent stated that young people should be taught how to protect themselves
      and 57% that teaching at school was insufficient. Main information sources were
      books/media; preferred sources were media, schools, and health professionals.
      Males scored higher on knowledge and were more susceptible to fear of STDs,
      society, and family; females showed greater compassion and interest in premarital
      testing and education to protect themselves. CONCLUSIONS: Alarming gaps in
      knowledge about transmission and curability put young Arabs at risk of
      contracting HIV. Fear and intolerant attitudes toward PLH were prevalent.
      HIV/AIDS education designed to raise knowledge and change attitudes, and
      respectful of community values, is urgently needed from media, schools, and
      health professionals.

PMID- 17531766
TI  - Patient and staff perspectives on the use of a computer counseling tool for HIV
      and sexually transmitted infection risk reduction.
AB  - PURPOSE: To explore use of an interactive health communication tool--"Computer
      Assessment and Risk Reduction Education (CARE) for STIs/HIV." METHODS: This was a
      mixed method study utilizing participant observation and in-depth interviews with
      patients (n = 43), and focus groups with staff (5 focus groups, n = 41) from 5
      clinics in 3 states (1 Planned Parenthood, 1 Teen, 2 STD, and 1 mobile van
      clinic). Data were managed using Atlas.ti. Inter-rater reliability of qualitative
      coding was .90. RESULTS: Users were 58% nonwhite with mean age 24.7 years (74% <
      25). Patients could use CARE with minimal to no assistance. Time for session
      completion averaged 29.6 minutes. CARE usefulness was rated an average of 8.2 on
      an ascending utility scale of 0 to 10. Patient themes raised as strengths were
      novelty, simplicity, confidentiality, personalization, and plan development,
      increased willingness to be honest, lack of judgment, and a unique opportunity
      for self-evaluation. Staff themes raised as strengths were enhanced data
      collection, handout customization, education standardization, behavioral priming,
      and expansion of services. Patient limitation themes included limited responses
      and lack of personal touch. Staff limitation themes were selecting users, cost,
      patient-provider role, privacy, and time for use. CONCLUSIONS: CARE was well
      received and easily usable by most (especially 18-25-year-olds). Patient and
      staff perceptions support the use of CARE as an adjunct to usual practice and as
      a method to expand services. Honesty, reduced time constraints, and lack of
      judgment associated with CARE appeared to enhance self-evaluation, which may
      prove an important component in moving patients forward in the behavior change
      process.

PMID- 17531767
TI  - Relationship of STD-related shame and stigma to female adolescents' condom
      protected intercourse.
AB  - PURPOSE: Shame and stigma associated with sexually transmitted diseases (STDs)
      are barriers to adolescents seeking prompt and appropriate diagnosis and
      treatment. However, little is known about how these constructs are related to STD
      protective behaviors, such as condom-protected intercourse. Thus, we
      prospectively examined the relationship between shame and stigma and condom use
      in adolescent females. METHODS: There were 192 African American females age 17.4
      +/- 1.7 years (range 15-21 years) recruited for the study from local teen
      oriented health clinics. At baseline, participants completed demographic and
      psychosocial measures (including STD-related shame and stigma), and chart- or
      laboratory-confirmed history of STDs was obtained. At 6 months follow-up, rate of
      condom-protected intercourse in past 14 days was assessed. Participants' baseline
      shame and stigma scores, prior history of STDs, and select demographic and
      theoretically important psychosocial variables were entered into a hierarchical
      linear regression model to predict condom-protected intercourse in the 14 days
      prior to the 6-month follow-up assessment. RESULTS: After controlling for
      variables identified in bivariate correlations, STD-related shame was
      significantly predictive of condom-protected intercourse in the 14 days prior to
      follow-up, with higher shame predicting higher rates of condom-protected
      intercourse. CONCLUSIONS: Future prevention efforts attempting to reduce
      adolescents' risks for STDs and HIV may benefit from addressing STD-related shame
      and stigma in addition to explicitly linking health-promoting behavior changes
      (condom use) to a decreased likelihood of future infection with STDs.

PMID- 17531768
TI  - Nonconsensual sexual experiences of adolescents in urban India.
AB  - PURPOSE: Research from developing countries suggests that nonconsensual sexual
      experiences are common, yet these experiences remain understudied. METHODS: We
      describe the prevalence and factors associated with nonconsensual sexual
      experiences of unmarried adolescents (583 boys and 474 girls), ages 15-19 years,
      from economically disadvantaged neighborhoods in Delhi, India. We also describe
      their reports of perpetrators. RESULTS: Thirty-two percent of boys and 42% of
      girls reported being touched against their will. After multivariate adjustment,
      both boys and girls who had ever worked (odds ratio [OR] = 1.76, p = .05 and OR =
      1.79, p = .004, respectively) and those who had a friend of the opposite gender
      (OR = 3.64, p = .0001 and OR = 2.19, p = .0001, respectively) were more likely to
      report the experience. The most commonly reported perpetrators were female
      friends for boys (60%) and strangers for girls (93%). Fifteen percent of boys and
      3% of girls reported that someone forcibly tried to have a physical relationship
      with them. Boys who had ever worked (OR = 3.73, p = .007) were more likely to
      report the experience. Both boys and girls who had a friend of the opposite sex
      were more likely to report attempted forced physical relationship (OR = 3.73, p =
      .0001 and OR = 3.41, p = .03, respectively). The most commonly reported
      perpetrators were female friends for boys (72%) and neighbors (60%) for girls.
      CONCLUSIONS: Nonconsensual sex is a common experience for these adolescents and
      there are important gender differences in experience and type of perpetrator. The
      findings underscore the need to develop programs that enable young people to
      prevent and cope with nonconsensual sexual experiences.

PMID- 17531769
TI  - Newly homeless youth typically return home.
AB  - Newly homeless adolescents from Melbourne, Australia (n = 165) and Los Angeles,
      United States (n = 261) were surveyed and followed for 2 years. Most newly
      homeless adolescents returned home (70% U.S., 47% Australia) for significant
      amounts of time (39% U.S., 17% Australia more than 12 months) within 2 years of
      becoming homeless.

PMID- 17531770
TI  - Eating habits among adolescents in rural Southern Appalachia.
AB  - A survey of 274 adolescents aged 14-16 years in rural Appalachia showed that
      unhealthy eating habits were prevalent. A few adolescents were teased about
      weight whereas 20.1% witnessed weight teasing almost everyday. Perception of
      parents' healthy eating and better social support for healthy eating were
      associated with healthier eating habits.

PMID- 17531771
TI  - Nasal symptoms are associated with school performance in adolescents.
AB  - Children with asthma and allergy have higher school absence rates than others,
      but little is known about their school performance. In a study of 9538
      adolescents, nasal symptoms severe enough to affect daily activity were
      associated with low-grade sum, particularly in adolescents using anti-allergy
      medication.

PMID- 17531772
TI  - Allogeneic bone marrow transplantation in models of experimental autoimmune
      encephalomyelitis: evidence for a graft-versus-autoimmunity effect.
AB  - Autologous hematopoietic stem cell transplantation (HSCT) is being explored in
      the treatment of severe multiple sclerosis (MS), and is based on the concept of
      "resetting" the immune system. The use of allogeneic HSCT may offer additional
      advantages, such as the replacement of the autoreactive immune compartment by
      healthy allogeneic cells and development of a graft-versus-autoimmunity (GVA)
      effect. However, in clinical practice, the genetic susceptibility to MS of
      allogeneic stem cell donors is generally unknown, and GVA may therefore be an
      important mechanism of action. Experimental autoimmune encephalomyelitis (EAE)
      susceptible and -resistant mouse strains were used to determine the roles of
      genetic susceptibility, level of donor-chimerism, and alloreactivity in the
      therapeutic potential of syngeneic versus allogeneic bone marrow transplant (BMT)
      for EAE. After transplantation and EAE induction, animals were evaluated for
      clinical EAE and ex vivo myelin oligodendrocyte glycoprotein-specific
      proliferation. Early after BMT, both syngeneic and allogeneic chimeras were
      protected from EAE development. On the longer term, allogeneic but not syngeneic
      BMT conferred protection, but this required high-level donor-chimerism from EAE
      resistant donors. Importantly, when EAE-susceptible donors were used, robust
      protection from EAE was obtained when active alloreactivity, induced by donor
      lymphocyte infusions, was provided. Our findings indicate the requirement of a
      sufficient level of donor-chimerism from a nonsusceptible donor in the
      therapeutic effect of allogeneic BMT. Importantly, the data indicate that,
      independently of genetic susceptibility, active alloreactivity is associated with
      a GVA effect, thereby providing new evidence to support the potential role of
      allogeneic BMT in the treatment of MS.

PMID- 17531773
TI  - Stem cell transplantation nephropathy: a report of six cases.
AB  - Stem cell transplantation (SCT) nephropathy is 1 cause of chronic kidney disease
      in patients after allogeneic SCT. It is a thrombotic microangiopathic syndrome
      characterized by raised creatinine, hypertension, and anemia. The difference with
      thrombotic thrombocytopenic purpura (TTP)-like syndromes is that it occurs later
      than 3 months after SCT, has marked renal dysfunction, and occurs in the absence
      of other complications or nephrotoxic medication. Total-body irradiation (TBI) in
      combination with previous chemotherapy is most likely the cause. We describe 6
      cases of SCT nephropathy that occurred in a cohort of 363 patients who received
      myeloablative allogeneic SCT. All patients had TBI with shielding of the kidneys.
      We discuss the course of the syndrome, treatment, and outcome of the patients.

PMID- 17531774
TI  - In vitro methotrexate as a practical approach to selective allodepletion.
AB  - Graft-versus-host disease (GVHD) is a major cause of transplant-related morbidity
      and mortality in recipients of allogeneic hematopoietic stem cell
      transplantation. As GVHD is mediated predominantly by alloreactive donor T cells,
      selective allodepletion from the graft may alleviate GVHD, whereas potentially
      maintaining other advantages conferred by donor T cells, such as graft survival,
      antiviral immunity, and graft-versus-leukemia effect. In this study, we evaluated
      the ability of methotrexate, a clinically approved antimetabolite drug, to
      deplete alloreactive T cells in HLA-mismatched mixed lymphocyte reactions (MLR).
      We observed that methotrexate could inhibit the proliferation of alloreactive T
      cells in primary in vitro MLR. On reexposure of methotrexate-treated cells to the
      same allostimulus, a significant reduction in the alloreactive immune response
      was observed, whereas responses to third-party allostimuli and viral antigens
      were preserved. Thus, our results provide preclinical evidence that in vitro
      methotrexate treatment results in specific allodepletion and may be used as an
      effective agent for preventing GVHD.

PMID- 17531775
TI  - Impact of cytogenetics on outcome of de novo and therapy-related AML and MDS
      after allogeneic transplantation.
AB  - Cytogenetics has an important impact on the prognosis of patients undergoing
      allogeneic hematopoietic stem cell transplantation (HSCT) for acute myelogenous
      leukemia (AML) or myelodysplastic syndromes (MDS). However, it is unclear whether
      currently accepted cytogenetic risk groups, which were established for patients
      treated mostly with standard therapy, are optimally discriminating for patients
      undergoing HSCT. Also, the impact of cytogenetics in the growing population of
      patients with therapy-related disease has not been completely elucidated. In this
      study, we retrospectively analyzed data on 556 patients with AML or MDS
      transplanted at our institution. We examined, in multivariate analyses, the
      contribution of cytogenetics to survival, relapse, and nonrelapse mortality for
      the 476 patients with de novo disease. We used these results to establish an
      optimal cytogenetic grouping scheme. We then applied this grouping scheme to the
      80 patients with therapy-related disease. Our proposed 3-group cytogenetic
      classification outperformed the established grouping schemes for both de novo and
      therapy-related disease. When classified by this new scheme, cytogenetics was the
      strongest prognostic factor for overall survival in our cohort, through its
      impact on the risk of relapse (and not on nonrelapse mortality). After accounting
      for cytogenetics, patients with therapy-related AML or MDS had an equivalent
      outcome to those with de novo disease. This study demonstrates the impact of
      cytogenetics on the risk of relapse and death for patients with both de novo and
      therapy-related disease undergoing transplantation; it also emphasizes the
      necessity of using cytogenetics to stratify patients entering clinical trials,
      and provides a system for doing so, which can be validated in a multi
      institutional database.

PMID- 17531776
TI  - Outcomes of unrelated umbilical cord blood transplantation for X-linked
      adrenoleukodystrophy.
AB  - Adrenoleukodystrophy (ALD) is an X-linked disorder caused by a defect in the
      metabolism of long chain fatty acids leading to demyelination, neurodegeneration,
      and death. The disease typically presents in young boys and adolescent boys.
      Allogeneic bone marrow transplantation has been used to halt progression of the
      disease. However, many patients lack suitable HLA- matched related donors and
      must rely on unmatched donors for a source of stem cells. The purpose of this
      study was to evaluate outcomes of unrelated donor umbilical cord blood
      transplantation after chemotherapy-based myeloablative conditioning and
      retrospectively determine if baseline studies correlate and help predict outcome.
      Between November 22, 1996, and November 3, 2005, 12 boys with X-linked ALD who
      lacked HL- matched related donors were referred to Duke University Medical Center
      for transplantation. These children were conditioned with myeloablative therapy
      including busulfan, cyclophosphamide, and antithymocyte globulin before receiving
      umbilical cord-blood transplants from unrelated donors. Baseline studies of
      neurophysiologic, neuroimaging, and neurodevelopmental status were performed and
      patients were subsequently evaluated for survival, engraftment, graft-versus-host
      disease, and neurodevelopmental outcomes. A substudy evaluated whether baseline
      neuroimaging and neurophysiologic studies correlated with cognitive and motor
      function and if these studies were predictive of posttransplantation outcomes.
      The umbilical cord blood grafts had normal levels of very long chain fatty acids.
      They delivered a median of 6.98 x 10(7) nucleated cells per kilogram of recipient
      body weight and were discordant for up to 4 of 6 HLA markers. Neutrophil
      engraftment occurred at a median of 22.9 days after transplantation. Three
      patients had grade II-IV acute graft-versus-host disease; 2 had extensive chronic
      graft-versus-host disease. Cumulative incidence of overall survival of the group
      at 6 months is 66.7% (95% confidence interval 39.9-93.3%). Median follow-up was
      3.3 years (range 12 days to 6.3 years). As previously reported with bone marrow
      transplantation, symptomatic patients faired poorly with lower survival and rapid
      deterioration of neurologic function. This study included 3 patients transplanted
      at a very young age (2.6-3.5 years) before the onset of clinical symptoms who
      continue to develop at a normal rate for 3-5 years posttransplant. Although
      baseline Loes scores correlated with cognitive and motor outcome,
      neurophysiologic studies failed to show statistically significant differences.
      Transplantation of boys with X-linked ALD using partial HLA-matched umbilical
      cord blood yields similar results to those previously reported after bone marrow
      transplantation. Superior outcomes were seen in neurologically asymptomatic boys
      less than 3.5 years of age at the time of transplantation. Baseline Loes scores
      were a strong predictor of cognitive and motor outcome.

PMID- 17531777
TI  - Major ABO blood group mismatch increases the risk for graft failure after
      unrelated donor hematopoietic stem cell transplantation.
AB  - Two hundred twenty-four patients with leukemia transplanted with an unrelated
      donor between 1991 and 2003 at the Karolinska University Hospital were analyzed
      according to association between graft failure and ABO, RhD, MNSs, and Kidd blood
      group antigen compatibility. Median age was 29 years (range: 0-55). Conditioning
      consisted of total-body irradiation or busulfan-based myeloablative conditioning.
      A bone marrow graft was given to 152 patients, and 72 patients received
      peripheral blood stem cells. Most patients received graft-versus-host disease
      prophylaxis with cyclosporine and MTX. Graft failure (GF) was seen in 6 (2.7%)
      patients. In the multivariate analysis major ABO mismatch (odds ratio [OR] 14.9,
      95% confidence interval [CI] 2.01-110, P = .008) and HLA-allele mismatch (6.42,
      1.19-34.8, P = .03) was significantly associated to GF. In patients with and
      without major ABO mismatch the incidence of GF was 7.5% and 0.6% (P = .02),
      respectively. Using an ABO major mismatched graft increases the risk for GF after
      unrelated donor hematopoietic stem cell transplantation.

PMID- 17531778
TI  - Bisphosphonate therapy for reduced bone mineral density in children with chronic
      graft-versus-host disease.
AB  - Reduced bone mineral density (BMD) occurs frequently in children after
      hematopoietic cell transplantation (HCT), but therapy for this complication is
      undefined. To determine the impact of bisphosphonate therapy on reduced BMD after
      HCT, we compared baseline and follow-up dual energy X-ray absorptiometry (DEXA)
      scans of 48 patients (controls) who received calcium and vitamin D to 18 patients
      who also received bisphosphonate therapy. Among the controls, median annualized
      increase in standardized BMD (sBMD) was 10% (range, -26% to +41%), but the
      deviation of sBMD from normal, as indicated by the Z-score, did not improve from
      baseline, -2.46 (range: -5.15 to -1.16) compared to follow-up, -2.79 (range: 
      5.76 to +0.07). For the bisphosphonate-treated patients, the median annualized
      increase in sBMD was 33% (range 3% to 147%, P = .0002) and the median Z-score
      improved from -3.57 (range: -5.13 to -0.86) at baseline, to -1.80 (-4.89 to
      +0.47) at follow-up (P = .06). The annualized median change in BMD Z-scores per
      year was +0.12 (-2.28 to +4.24) among the controls and +1.43 (-0.29 to +3.72) for
      the bisphosphonate group (P = .0002). The greatest improvement in BMD was
      observed in children who received therapy with bisphosphonates.

PMID- 17531779
TI  - High-content flow cytometry and temporal data analysis for defining a cellular
      signature of graft-versus-host disease.
AB  - Acute graft-versus-host disease (GVHD) is diagnosed by clinical and histologic
      criteria that are often nonspecific and typically apparent only after the disease
      is well established. Because GvHD is mediated by donor T cells and other immune
      effector cells, we sought to determine whether changes within a wide array of
      peripheral blood lymphocyte populations could predict the development of GvHD.
      Peripheral blood samples from 31 patients undergoing allogeneic blood and marrow
      transplant were analyzed for the proportion of 121 different subpopulations
      defined by 4-color combinations of lymphocyte phenotypic and activation markers
      at progressive time points posttransplant. Samples were processed using a newly
      developed high content flow cytometry technique and subjected to a spline- and
      functional linear discriminant analysis (FLDA)-based temporal analysis technique.
      This strategy identified a consistent posttransplant increase in the proportion
      and extent of fluctuation of CD3+CD4+CD8beta+ cells in patients who developed
      GVHD compared to those that did not. Although larger prospective clinical studies
      will be necessary to validate these results, this study demonstrates that high
      content flow cytometry coupled with temporal analysis is a powerful approach for
      developing new diagnostic tools, and may be useful for developing a sensitive and
      specific predictive test for GVHD.

PMID- 17531780
TI  - Sirolimus as part of immunosuppressive therapy for refractory chronic graft
      versus-host disease.
AB  - Many patients receiving allogeneic stem cells develop chronic graft-versus-host
      disease (cGVHD), which remains as the main cause of morbidity and mortality.
      Although the first line of therapy is generally with steroids, it is not well
      known how to manage refractory cases. Those patients are usually treated with
      alternative experimental agents. Sirolimus (Rapamycin), a new immunosuppressive
      agent, inhibits signal transduction and cell cycle progression after binding to
      FKBP12. We report a retrospective analysis with sirolimus in transplant
      recipients with cGVHD refractory to previous immunosuppressive therapy. Forty
      seven patients with refractory or relapsed cGVHD were treated with the
      combination of sirolimus and calcineurin inhibitors (n = 33), mycophenolate (n =
      9), or prednisone (n = 5). Thirty-eight of 47 (81%) patients had clinical
      responses (complete = 18, partial = 20). The main toxicity was mild renal
      failure, particularly at the start of therapy. Four patients who presented
      thrombotic microangiopathy were managed with plasmapheresis and the
      discontinuation of sirolimus and calcineurin inhibitors. Statistical analysis
      showed the type of cGVHD onset and presirolimus clinical status as the main
      variables influencing the response to treatment. The Kaplan-Meier estimate of
      survival was 57.4% at 3 years. The current study shows the efficacy and safety of
      sirolimus in refractory cGVHD patients. Further investigation is warranted to
      elucidate the role of sirolimus in cGVHD, and find the best combination
      (sirolimus + calcineurin inhibitors versus others) for therapeutic use.

PMID- 17531781
TI  - Ex vivo expansion and prophylactic infusion of CMV-pp65 peptide-specific
      cytotoxic T-lymphocytes following allogeneic hematopoietic stem cell
      transplantation.
AB  - Cytomegalovirus reactivation and infection post-allogeneic hematopoietic stem
      cell transplant continue to cause morbidity and mortality. Current pharmacologic
      therapies are limited by side effects. Adoptive transfer of ex vivo generated
      cytomegalovirus-specific T cells has the potential to restore immunity, prevent
      cytomegalovirus, and circumvent the need for pharmacologic therapies. We have
      generated donor-derived cytomegalovirus-specific cytotoxic T cells using
      dendritic cells pulsed with the HLA-A2 restricted nonapeptide NLVPMVATV (NLV)
      derived from the cytomegalovirus-pp65 protein. These cytotoxic T cells have been
      given prophylactically to 9 recipients aged 4 to 65 years on or after day 28 post
      allogeneic hematopoietic stem cell transplant. Only 2 of 9 recipients received T
      cell depletion in vivo or in vitro. There were no immediate adverse reactions to
      the infusions. During 97-798 days of follow-up, 2 recipients developed
      cytomegalovirus reactivation; neither developed cytomegalovirus disease or
      required pharmacotherapy. Three recipients developed acute graft versus host
      disease after infusion. Two recipients died, 1 from thrombotic thrombocytopenia
      purpura secondary to cyclosporine, 1 from complications of graft versus host
      disease. A transient increase in numbers of cytomegalovirus-specific T cells
      demonstrated by NLV-tetramer binding was seen in 6 recipients. Prophylactic
      adoptive transfer of NLV-specific T cells is safe and may be effective in
      preventing cytomegalovirus reactivation.

PMID- 17531782
TI  - A single-center pilot validation study of a new chronic GVHD skin scoring system.
AB  - The use of a quantifiable and reproducible measurement tool for skin
      manifestations of chronic graft-versus-host disease (cGVHD) is key for the
      successful assessment and documentation of therapeutic response. Skin scoring
      methods for use in clinical trials have not been validated for application in
      patients suffering from cGVHD. For this purpose we performed a prospective single
      center pilot study to validate a skin-scoring tool developed at our institution
      for evaluating cutaneous involvement of cGVHD approximately 10 years ago. It
      combines percentage of involved body surface area (BSA) divided into 10 separate
      anatomic regions with manifestations of cGVHD coded from 0 (normal skin) to 4
      (hidebound skin, unmovable sclerosis). Sixteen patients were examined separately
      by 4 trained physicians 3 times on 2 consecutive days for a total of 192
      individual skin assessments; intraobserver and interobserver reliability were
      calculated. Good to excellent intraclass correlation coefficients (ICC) were
      obtained in almost all scores including erythematous lesions in areas with scores
      3 and 4 for all observers. Moderate to good interrater reliability for observers
      1 to 4 was seen in lesions with scores 0, 3, and 4, respectively. A marked
      improvement of interrater reliability in all scores and examinations was observed
      when ICCs were calculated only for the more experienced observers 1 to 3. This
      New Chronic GVHD Skin score is a reproducible, accurate, feasible, and
      inexpensive tool for use in selected clinical trials of chronic cutaneous GVHD.
      Further studies with larger patient numbers and validation of this new tool for
      assessment of treatment response are warranted.

PMID- 17531783
TI  - Long-term outcome of unrelated donor transplantation for AML using myeloablative
      conditioning incorporating pretransplant Alemtuzumab.
AB  - The outcome of 55 patients who underwent matched unrelated donor (MUD)
      transplantation for acute myelogenous leukemia (AML) following a conditioning
      regimen of cyclophosphamide and total-body irradiation (TBI) with the addition of
      Alemtuzumab 10 mg/kg/day on days -5 to -1 is described. All patients received
      graft-versus-host disease (GVHD) prophylaxis with cyclosporine as well as 3 doses
      of posttransplant methotrexate. Forty-one patients were transplanted in complete
      remission (CR) (20 in CR1, 20 in CR2, and 1 in CR3), and 14 were not in remission
      at the time of transplantation as they were refractory to chemotherapy either at
      induction or at relapse. The group consisted of adult patients with a median age
      of 37 years. Thirty-five patients were fully matched at HLA-A, -B, -C, and -DRB1.
      All patients engrafted and there were no cases of graft rejection. Grade II-IV
      acute GVHD occurred in only 2 patients. Chronic GVHD developed in 30% of patients
      but was extensive in only 3 cases. The predicted TRM was 11% at day 100 and 26%
      at 1 year. In multivariate analysis the receipt of an HLA mismatched transplant
      was associated with a higher transplant-related mortality (TRM) (55% versus 15%).
      Twelve of the 14 transplant-related deaths were due to infection. The 5-year
      cumulative incidence of relapse was 36% for the whole group and 28% for patients
      in CR at transplantation. The 5-year cumulative survival for the whole group was
      38% and was 49% for those in remission at transplantation. Seven of the 12
      patients transplanted in CR1 with adverse risk cytogenetics remain alive and in
      remission, and the predicted 5-year overall survival (OS) for this group is 50%.
      These results support the use of Alemtuzumab for unrelated donor hematopoietic
      stem cell transplant (HSCT) for poor risk AML in CR1 and for relapsed AML in CR2.
      The addition of Alemtuzumab is highly effective in preventing both rejection and
      severe acute and extensive chronic GVHD without an increased relapse risk.

PMID- 17531784
TI  - Reconstitution of natural killer cell receptor repertoires after unmanipulated
      HLA-mismatched/haploidentical blood and marrow transplantation: analyses of
      CD94:NKG2A and killer immunoglobulin-like receptor expression and their
      associations with clinical outcome.
AB  - The effect of natural killer (NK) cell alloreactivity on the outcome of
      haploidentical hematopoietic stem cell transplantation (HSCT), with or without in
      vitro T cell depletion, remains controversial. Killer immunoglobulin-like
      receptors (KIRs) recognize human leukocyte antigen C and B epitopes on target
      cells, thereby regulating NK cell activity. To examine the recovery of CD94:NKG2A
      and KIR (CD158a, CD158b, and CD158e) expression by NK cells, we used flow
      cytometry to evaluate samples from 24 patients and their donors before and in the
      year following unmanipulated HLA-haploidentical/mismatched blood and marrow
      transplantation. Linear regression analysis demonstrated that NKG2A recovery was
      inversely correlated with CD158b recovery in the year following transplant. The
      doses of T cell subgroups CD4+ and CD8+ were inversely associated with CD158a and
      CD158e expression during the 2 months following transplantation. Moreover,
      patients with grades II-IV acute graft-versus-host disease (aGVHD) or who
      received "high" doses of T cells (>1.37 x 10(8)/kg) showed delayed recovery of
      KIRs during the 2 months following transplantation. Univariate analysis showed
      that patients with high CD94 expression by day 60 (>90%) or who received donors
      with high CD94 expression (>80%) were associated with higher transplantation
      related mortality (P = .006 or .067, respectively) and poorer leukemia-free
      survival (P = .012 or .094, respectively). Thus, the occurrence of aGVHD or the
      receipt of high doses of T cells in the allograft altered KIR reconstitution.
      Furthermore, high levels of CD94 expression in donors or in recipients by day 60
      might be a good predictor for poor prognosis.

PMID- 17531785
TI  - Long-term outcome of Hodgkin disease patients following high-dose busulfan,
      etoposide, cyclophosphamide, and autologous stem cell transplantation--a similar
      experience.

PMID- 17531786
TI  - Carbon dioxide signalling in plant leaves.
AB  - The role of carbon dioxide (CO(2)) as a signal in biochemical regulation networks
      of plants is fathomed. Transport mechanisms of CO(2) and HCO3- are surveyed,
      which are the prerequisite for signalling. A CO(2) sensor is not known to date,
      but any reaction where CO(2)/HCO3- is a substrate can be a candidate. Carbon
      concentrating mechanisms, e.g., in higher plants C(4)-photosynthesis and
      crassulacean acid metabolism (CAM), generate high internal CO(2) concentrations,
      important for photosynthesis, but also as a basis for signalling via diffusion of
      CO(2). Spatiotemporal dynamics of desynchronization/synchronization of
      photosynthetic activity over leaves can be followed by chlorophyll fluorescence
      imaging. One example of desynchronization is based on patchiness of stomatal
      opening/closing in heterobaric leaves due to anatomic constraints of lateral
      CO(2) diffusion. During CAM, largely different internal CO(2) concentrations
      prevail in the leaves, offering opportunities to study the effect of lateral
      diffusion of CO(2) in synchronizing photosynthetic activity over the entire
      leaves.

PMID- 17531787
TI  - Altered processing of sensorimotor feedback in schizophrenia.
AB  - Schizophrenia is characterized by an altered sense of the reality, associated
      with hallucinations and delusions. Some theories suggest that schizophrenia is
      related to a deficiency of the system that generates information about the
      sensory consequences of the actions realized by the subject. This system monitors
      the reafferent information resulting from an action and allows its anticipation.
      In the present study, we examined visual-event-related potentials (ERPs)
      generated by a sensorimotor task in 15 patients with schizophrenia and 15 normal
      controls. The visual feedback from hand movements performed by the subjects was
      experimentally distorted. Behavioral results showed that patients were impaired
      in recognizing their own movements. The ERP signal in patients also differed from
      those of control subjects. In patients, the ERP waveform was affected during the
      early part of the response (200 ms). This early effect in schizophrenic patients
      reveals a modified processing of the visual consequence of their actions.

PMID- 17531788
TI  - Life cycle of the earthworm Octodrilus complanatus (Oligochaeta, Lumbricidae).
AB  - The earthworm Octodrilus complanatus (Duges, 1828) is a large-sized species often
      found in grasslands and pastures, with a wide distribution area in Europe and
      North Africa. In order to determine the characteristics of its life cycle,
      earthworms of this species were cultured from hatching until they reached
      maturity. Development rates, cocoon production, and incubation period were
      recorded under controlled conditions. On average, individuals of O. complanatus
      reared in isolation from hatching reached maturity at day 150 and body weight at
      maturity ranged between 6 and 8 g. The cocoon incubation period was 66 days, and
      only one individual hatched from each cocoon, with a mean hatchability of 55%.
      Reproductive rate showed by O. complanatus after mating was of 52 cocoons per
      earthworm per year. The results showed that the life cycle of O. complanatus was
      characterized by both low growth rates and low fecundity. Specific features in
      life history traits of O. complanatus were compared with those of species of the
      genus Octodrilus and other related earthworms.

PMID- 17531789
TI  - Induction of callus formation from difficile date palm protoplasts by means of
      nurse culture.
AB  - We report here for the first time callus formation from protoplasts in date palm
      (Phoenix dactylifera L.). Protoplasts were isolated from young leaves of
      offshoots and embryogenic calli in Deglet nour and Takerboucht genotypes. The
      protoplast yield depended on genotype, donor plant material, mixture of enzyme
      solution, and incubation time. With regard to the donor material, the best
      response was obtained with callus. Cell division was induced in both liquid
      culture and nurse culture. The best donor material for cell division was callus
      and the best response was obtained with the feeder layer, which induced a
      division rate of 30% in Deglet nour and 15% in Takerboucht genotypes. The
      dividing cells developed to microcalli on the feeder layer; the microcalli
      developed to calli on modified MS medium; however, the calli failed to regenerate
      into roots or shoots.

PMID- 17531790
TI  - [Storage proteins from seeds of Pinus pinea L].
AB  - The Mediterranean stone pine Pinus pinea L. (gymnosperm, Pinaceae) is much
      appreciated for its seed production, widely used in food preparation in the
      Mediterranean Basin. Seeds contain 25% proteins on a dry-weight basis. Pinus
      pinea accumulate globulins as major storage proteins in seeds (75% of total
      storage proteins), composed of several subunits of 10 to 150 kDa, revealed by SDS
      PAGE. The albumin fraction (15%) represents three subunits of 14, 24 and 46 kDa.
      Glutelins, the least soluble fraction, represents a small proportion (10%). Their
      constitutive units have frequent PM of 43 kDa. Prolamins also represent a very
      small percentage (1 to 2%).

PMID- 17531791
TI  - [Toxicity of hexachlorobenzene in Meriones unguiculatus: effects on thyroid and
      liver].
AB  - The effect of in vivo administered hexachlorobenzene (HCB) on liver and thyroid
      was studied on Meriones unguiculatus. HCB (1.6, 4, and 16 mg/kg of body weight)
      has been administered orally to meriones for 30 days. At the end of the
      experiment, the body weight of the animals did not show significant change.
      However, the higher dose of HCB treatment led to a pronounced hepatic hypertrophy
      comparatively to controls. Histological observations revealed many
      cytomorphological alterations. Cellular necrosis, periportal, and centrolobular
      vein congestion and cytoplasmic vacuolisation were noted and correlated with the
      administered doses of HCB. The higher dose of HCB induced modifications in the
      activities of hepatic transaminases and on thyroid hormones levels: ALAT activity
      level was more pronounced in males (170+/-24.7 U/l vs. 52.66+/-8.29 U/l in
      controls) than in females (120+/-12.47 U/l vs. 56+/-5 U/l in controls). However,
      ASAT activity increased significantly only in females (259+/-29 U/l vs. 244.66+/
      18 U/l in controls). Plasma total triiodothyronine (TT3) and total thyroxine
      (TT4) levels seemed to be sex-dependent in intoxicated animals, since TT4
      decreased significantly in males (21.95+/-7.46 nmol/l vs. 40.59+/-1.08 nmol/l in
      controls) and TT3 in females (1.42+/-0.11 nmol/l vs. 3.96+/-0.48 nmol/l in
      controls).

PMID- 17531792
TI  - Exchange potentials of phosphorus between sediments and water coupled to alkaline
      phosphatase activity and environmental factors in an oligo-mesotrophic reservoir.
AB  - We investigated the exchange potentials of phosphates at the water-sediment
      interface together with in situ benthic-chamber fractionated alkaline phosphatase
      activity and bacteria estimates during September and October 1998 at two
      stations: station 1, which received immediately the urban inputs from the
      Taounate city, and station 2, located in the centre of the Sahela reservoir
      (Morocco). The results showed that low oxygenation enhanced both the bacterial
      abundance and the alkaline phosphatase activity. Size-fractionated (0.65-100
      microm) bacteria attached to dead organic matter together with algae and
      zooplankton contributed strongly (78%) to the total alkaline phosphatase
      synthesis in the two sampled stations, suggesting that attachment to organic
      particles stimulated phosphatase activities. The appearance of anoxic conditions
      and the decrease of pH supported the dissolution of particulate phosphorus and
      the release of soluble reactive phosphorus. This latter, together with persisting
      discharges of organic matter, sewage, and olive mill waste will exacerbate the
      eutrophication of the reservoir.

PMID- 17531793
TI  - [Temporal and spatial fluctuations in bacterial abundances in four basins of a
      landfill leachate treatment (Etueffont, France)].
AB  - The seasonal distribution of bacterial communities was assessed in a landfill
      leachate station located in Etueffont (Territoire de Belfort, France). Water
      samples were taken monthly from May 1998 to May 1999 from both the gross leachate
      and four lagooning basins. Bacterial numbers varied from 0.04x10(6) to 0.35x10(6)
      cells ml(-1) (m+/-sd=0.13x10(6)+/-0.12x10(6) cells ml(-1)). They decreased from
      the first to the last basin and were overall lower than those reported in
      literature for aquatic systems with comparable organic matter content. This may
      be ascribed to the leachate toxicity on bacteria.

PMID- 17531794
TI  - Observations on the remarkable disrupted geographical distribution of the genus
      Microbuthus Kraepelin, 1898 in North Africa, with the description of a new
      species from Egypt (Scorpiones, Buthidae).
AB  - A disrupted Perisaharan pattern of distribution is confirmed for the species of
      the genus Microbuthus Kraepelin, 1898. A new species, Microbuthus flavorufus sp.
      n., is described from Egypt, raising the total number of known species of the
      genus to five.

PMID- 17531795
TI  - Molecular phylogeny in mytilids supports the wooden steps to deep-sea vents
      hypothesis.
AB  - Molecular data were used to study the diversity of mytilids associated with
      sunken-woods sampled in the Solomon Islands and discuss the 'wooden steps to deep
      sea vent' hypothesis proposed by Distel et al. First, COI data used in a
      barcoding approach confirm the presence of four distinct species. Analyses of the
      18S rDNA and COI dataset then confirmed that these sunken-wood mytilids belonged
      to a monophyletic group including all species from deep-sea reducing
      environments. Finally, we analyzed the relationships within this monophyletic
      group that include the Bathymodiolinae using a COI dataset and a combined
      analysis of mitochondrial COI and ND4 genes and nuclear rDNA 18S and 28S. Our
      study supported the 'wooden steps to deep-sea vent' hypothesis: one of the sunken
      wood species had a basal position within the Bathymodiolionae, and all described
      vent and seep mussels included in our analyses were derived taxa within
      Bathymodiolinae.

PMID- 17531796
TI  - Comparative analysis of eubacterial DNA polymerase III alpha subunits.
AB  - DNA polymerase III is one of the five eubacterial DNA polymerases that is
      responsible for the replication of DNA duplex. Among the ten subunits of the DNA
      polymerase III core enzyme, the alpha subunit catalyzes the reaction for
      polymerizing both DNA strands. In this study, we extracted genomic sequences of
      the alpha subunit from 159 sequenced eubacterial genomes, and carried out
      sequence-based phylogenetic and structural analyses. We found that all
      eubacterial genomes have one or more alpha subunits, which form either homodimers
      or heterodimers. Phylogenetic and domain structural analyses as well as copy
      number variations of the alpha subunit in each bacterium indicate the
      classification of alpha subunit into four basic groups: polC, dnaE1, dnaE2, and
      dnaE3. This classification is of essence in genome composition analysis. We also
      consolidated the naming convention to avoid further confusion in gene
      annotations.

PMID- 17531797
TI  - High-sensitivity transcriptome data structure and implications for analysis and
      biologic interpretation.
AB  - Novel microarray technologies such as the AB1700 platform from Applied Biosystems
      promise significant increases in the signal dynamic range and a higher
      sensitivity for weakly expressed transcripts. We have compared a representative
      set of AB1700 data with a similarly representative Affymetrix HG-U133A dataset.
      The AB1700 design extends the signal dynamic detection range at the lower bound
      by one order of magnitude. The lognormal signal distribution profiles of these
      high-sensitivity data need to be represented by two independent distributions.
      The additional second distribution covers those transcripts that would have gone
      undetected using the Affymetrix technology. The signal-dependent variance
      distribution in the AB1700 data is a non-trivial function of signal intensity,
      describable using a composite function. The drastically different structure of
      these high-sensitivity transcriptome profiles requires adaptation or even
      redevelopment of the standard microarray analysis methods. Based on the
      statistical properties, we have derived a signal variance distribution model for
      AB1700 data that is necessary for such development. Interestingly, the dual
      lognormal distribution observed in the AB1700 data reflects two fundamentally
      different biologic mechanisms of transcription initiation.

PMID- 17531798
TI  - Comparative analysis of splice site regions by information content.
AB  - We have applied concepts from information theory for a comparative analysis of
      donor (gt) and acceptor (ag) splice site regions in the genes of five different
      organisms by calculating their mutual information content (relative entropy) over
      a selected block of nucleotides. A similar pattern that the information content
      decreases as the block size increases was observed for both regions in all the
      organisms studied. This result suggests that the information required for
      splicing might be contained in the consensus of approximately 6-8 nt at both
      regions. We assume from our study that even though the nucleotides are showing
      some degrees of conservation in the flanking regions of the splice sites, certain
      level of variability is still tolerated, which leads the splicing process to
      occur normally even if the extent of base pairing is not fully satisfied. We also
      suggest that this variability can be compensated by recognizing different splice
      sites with different spliceosomal factors.

PMID- 17531799
TI  - Prediction of GPCR-G protein coupling specificity using features of sequences and
      biological functions.
AB  - Understanding the coupling specificity between G protein-coupled receptors
      (GPCRs) and specific classes of G proteins is important for further elucidation
      of receptor functions within a cell. Increasing information on GPCR sequences and
      the G protein family would facilitate prediction of the coupling properties of
      GPCRs. In this study, we describe a novel approach for predicting the coupling
      specificity between GPCRs and G proteins. This method uses not only GPCR
      sequences but also the functional knowledge generated by natural language
      processing, and can achieve 92.2% prediction accuracy by using the C4.5
      algorithm. Furthermore, rules related to GPCR-G protein coupling are generated.
      The combination of sequence analysis and text mining improves the prediction
      accuracy for GPCR-G protein coupling specificity, and also provides clues for
      understanding GPCR signaling.

PMID- 17531800
TI  - A network partition algorithm for mining gene functional modules of colon cancer
      from DNA microarray data.
AB  - Computational analysis is essential for transforming the masses of microarray
      data into a mechanistic understanding of cancer. Here we present a method for
      finding gene functional modules of cancer from microarray data and have applied
      it to colon cancer. First, a colon cancer gene network and a normal colon tissue
      gene network were constructed using correlations between the genes. Then the
      modules that tended to have a homogeneous functional composition were identified
      by splitting up the network. Analysis of both networks revealed that they are
      scale-free. Comparison of the gene functional modules for colon cancer and normal
      tissues showed that the modules' functions changed with their structures.

PMID- 17531801
TI  - VGIchan: prediction and classification of voltage-gated ion channels.
AB  - This study describes methods for predicting and classifying voltage-gated ion
      channels. Firstly, a standard support vector machine (SVM) method was developed
      for predicting ion channels by using amino acid composition and dipeptide
      composition, with an accuracy of 82.89% and 85.56%, respectively. The accuracy of
      this SVM method was improved from 85.56% to 89.11% when combined with PSI-BLAST
      similarity search. Then we developed an SVM method for classifying ion channels
      (potassium, sodium, calcium, and chloride) by using dipeptide composition and
      achieved an overall accuracy of 96.89%. We further achieved a classification
      accuracy of 97.78% by using a hybrid method that combines dipeptide-based SVM and
      hidden Markov model methods. A web server VGIchan has been developed for
      predicting and classifying voltage-gated ion channels using the above approaches.

PMID- 17531802
TI  - KaKs_Calculator: calculating Ka and Ks through model selection and model
      averaging.
AB  - KaKs_Calculator is a software package that calculates nonsynonymous (Ka) and
      synonymous (Ks) substitution rates through model selection and model averaging.
      Since existing methods for this estimation adopt their specific mutation
      (substitution) models that consider different evolutionary features, leading to
      diverse estimates, KaKs_Calculator implements a set of candidate models in a
      maximum likelihood framework and adopts the Akaike information criterion to
      measure fitness between models and data, aiming to include as many features as
      needed for accurately capturing evolutionary information in protein-coding
      sequences. In addition, several existing methods for calculating Ka and Ks are
      also incorporated into this software.

PMID- 17531803
TI  - Puzzle plugged by protein pore plasticity.

PMID- 17531804
TI  - The oxazolidinone class of drugs find their orientation on the ribosome.

PMID- 17531805
TI  - wRAPing up the end to prevent telomere fusions.

PMID- 17531806
TI  - Identification of a molecular target for the Yersinia protein kinase A.
AB  - Pathogenic bacteria of the genus Yersinia employ a type III secretion system to
      inject bacterial effector proteins directly into the host cytosol. One of these
      effectors, the Yersinia serine/threonine protein kinase YpkA, is an essential
      virulence determinant involved in host actin cytoskeletal rearrangements and in
      inhibition of phagocytosis. Here we report that YpkA inhibits multiple Galphaq
      signaling pathways. The kinase activity of YpkA is required for Galphaq
      inhibition. YpkA phosphorylates Ser47, a key residue located in the highly
      conserved diphosphate binding loop of the GTPase fold of Galphaq. YpkA-mediated
      phosphorylation of Ser47 impairs guanine nucleotide binding by Galphaq. Y.
      pseudotuberculosis expressing wild-type YpkA, but not a catalytically inactive
      YpkA mutant, interferes with Galphaq-mediated signaling pathways. Identification
      of a YpkA-mediated phosphorylation site in Galphaq sheds light on the
      contribution of the kinase activity of YpkA to Yersinia pathogenesis.

PMID- 17531807
TI  - Allosteric signaling and a nuclear exit strategy: binding of UL25/UL17
      heterodimers to DNA-Filled HSV-1 capsids.
AB  - UL25 and UL17 are two essential minor capsid proteins of HSV-1, implicated in DNA
      packaging and capsid maturation. We used cryo-electron microscopy to examine
      their binding to capsids, whose architecture observes T = 16 icosahedral
      geometry. C-capsids (mature DNA-filled capsids) have an elongated two-domain
      molecule present at a unique, vertex-adjacent site that is not seen at other
      quasiequivalent sites or on unfilled capsids. Using SDS-PAGE and mass
      spectrometry to analyze wild-type capsids, UL25 null capsids, and denaturant
      extracted capsids, we conclude that (1) the C-capsid-specific component is a
      heterodimer of UL25 and UL17, and (2) capsids have additional populations of UL25
      and UL17 that are invisible in reconstructions because of sparsity and/or
      disorder. We infer that binding of the ordered population reflects structural
      changes induced on the outer surface as pressure builds up inside the capsid
      during DNA packaging. Its binding may signal that the C-capsid is ready to exit
      the nucleus.

PMID- 17531808
TI  - Regulation of glucose partitioning by PAS kinase and Ugp1 phosphorylation.
AB  - The ability of cells to recognize and respond to specific metabolic deficiencies
      is required for all forms of life. We have uncovered a system in the yeast S.
      cerevisiae that, in response to a perceived deficiency in cell wall glucan,
      alters partitioning of glucose toward glucan synthesis and away from glycogen
      synthesis. The paralogous yeast PAS kinases Psk1 and Psk2 phosphorylate UDP
      glucose pyrophosphorylase (Ugp1), the primary producer of UDP-glucose, the
      glucose donor for glucan biosynthesis. Unexpectedly, phosphorylation of Ugp1 does
      not affect its catalytic activity but instead alters the terminal destination of
      the UDP-glucose it generates. Phosphorylated Ugp1 is required for intensive
      glucan production, and inability to phosphorylate Ugp1 is associated with a weak
      cell wall, decreased glucan content, and increased glycogen content. We provide
      data indicating that phosphorylation by Psk1 or Psk2 targets Ugp1 to the cell
      periphery, where the UDP-glucose it produces is in proximity to the site of
      glucan synthesis. We propose that regulation of glucose partitioning by altered
      enzyme and substrate localization is a rapid and potent response to metabolic
      deficiency.

PMID- 17531809
TI  - Determining the conductance of the SecY protein translocation channel for small
      molecules.
AB  - The channel formed by the SecY complex must maintain the membrane barrier for
      ions and other small molecules during the translocation of membrane or secretory
      proteins. We have tested the permeability of the channel by using planar bilayers
      containing reconstituted purified E. coli SecY complex. Wild-type SecY complex
      did not show any conductance for ions or water. Deletion of the "plug," a short
      helix normally located in the center of the SecY complex, or modification of a
      cysteine introduced into the plug resulted in transient channel openings; a
      similar effect was seen with a mutation in the pore ring, a constriction in the
      center of the channel. Permanent channel opening occurred when the plug was moved
      out of the way by disulfide-bridge formation. These data show that the resting
      channel on its own forms a barrier for small molecules, with both the pore ring
      and the plug required for the seal; channel opening requires movement of the
      plug.

PMID- 17531810
TI  - The plug domain of the SecY protein stabilizes the closed state of the
      translocation channel and maintains a membrane seal.
AB  - Proteins are translocated across membranes through a channel that is formed by
      the prokaryotic SecY or eukaryotic Sec61 complex. The crystal structure of the
      SecY channel from M. jannaschii revealed a plug domain that appears to seal the
      channel in its closed state. However, the role of the plug remains unclear,
      particularly because plug deletion mutants in S. cerevisiae are functional. Here,
      we demonstrate that plug deletion mutants in E. coli SecY are also functional and
      even efficiently translocate proteins with defective or missing signal sequences.
      The crystal structures of equivalent plug deletions in SecY of M. jannaschii show
      that, although the overall structures are maintained, new plugs are formed. These
      lack many interactions that normally stabilize the closed channel, explaining why
      the channels can open for proteins with signal-sequence mutations. Our data show
      that the plug domain is required to maintain a closed state of the channel and
      suggest a mechanism for channel gating.

PMID- 17531811
TI  - RNA helicase A interacts with RISC in human cells and functions in RISC loading.
AB  - RNA interference is a conserved pathway of sequence-specific gene silencing that
      depends on small guide RNAs and the action of proteins assembled in the RNA
      induced silencing complex (RISC). Minimally, the action of RISC requires the
      endonucleolytic slicer activity of Argonaute2 (Ago2) directed to RNA targets
      whose sequences are complementary to RISC-incorporated small RNA. To identify
      RISC components in human cells, we developed an affinity-purification strategy to
      isolate siRNA-programmed RISC. Here we report the identification of RNA helicase
      A (RHA) as a human RISC-associated factor. We show that RHA interacts in human
      cells with siRNA, Ago2, TRBP, and Dicer and functions in the RNAi pathway. In RHA
      depleted cells, RNAi was reduced as a consequence of decreased intracellular
      concentration of active RISC assembled with the guide-strand RNA and Ago2. Our
      results identify RHA as a RISC component and demonstrate that RHA functions in
      RISC as an siRNA-loading factor.

PMID- 17531812
TI  - Evolutionarily conserved multisubunit RBL2/p130 and E2F4 protein complex
      represses human cell cycle-dependent genes in quiescence.
AB  - The mammalian Retinoblastoma (RB) family including pRB, p107, and p130 represses
      E2F target genes through mechanisms that are not fully understood. In D.
      melanogaster, RB-dependent repression is mediated in part by the multisubunit
      protein complex Drosophila RBF, E2F, and Myb (dREAM) that contains homologs of
      the C. elegans synthetic multivulva class B (synMuvB) gene products. Using an
      integrated approach combining proteomics, genomics, and bioinformatic analyses,
      we identified a p130 complex termed DP, RB-like, E2F, and MuvB (DREAM) that
      contains mammalian homologs of synMuvB proteins LIN-9, LIN-37, LIN-52, LIN-54,
      and LIN-53/RBBP4. DREAM bound to more than 800 human promoters in G0 and was
      required for repression of E2F target genes. In S phase, MuvB proteins
      dissociated from p130 and formed a distinct submodule that bound MYB. This work
      reveals an evolutionarily conserved multisubunit protein complex that contains
      p130 and E2F4, but not pRB, and mediates the repression of cell cycle-dependent
      genes in quiescence.

PMID- 17531813
TI  - Cdc18 enforces long-term maintenance of the S phase checkpoint by anchoring the
      Rad3-Rad26 complex to chromatin.
AB  - DNA replication is initiated by recruitment of Cdc18 to origins. During S phase,
      CDK-dependent destruction of Cdc18 occurs. We show that when DNA replication
      stalls, Cdc18 persists in a chromatin-bound complex including the checkpoint
      kinases Rad3 and Rad26. Rad26 directly binds Cdc18 and is required for Rad3
      recruitment to chromatin. Depletion of Cdc18 when DNA replication is stalled
      leads to release of Rad3 and Rad26 from chromatin and entry into an aberrant
      mitosis even though replication intermediates can still be detected. These
      findings indicate that Cdc18 plays a pivotal role in checkpoint maintenance by
      anchoring the Rad3-Rad26 complex to chromatin. Cdc18 persistence during DNA
      replication arrest requires the S phase checkpoint that inhibits the S phase CDK.
      We propose that S phase arrest activates the S phase checkpoint blocking mitosis
      onset and inhibiting Cdc18 degradation, and that the stabilized Cdc18, in turn,
      anchors Rad3 to chromatin to ensure long-term checkpoint maintenance.

PMID- 17531814
TI  - The N terminus of Saccharomyces cerevisiae Msh6 is an unstructured tether to
      PCNA.
AB  - The eukaryotic MutS homolog complexes, Msh2-Msh6 and Msh2-Msh3, recognize
      mismatched bases in DNA during mismatch repair (MMR). The eukaryote-specific N
      terminal regions (NTRs) of Msh6 and Msh3 have not been characterized other than
      by demonstrating that they contain an N-terminal PCNA-interacting motif. Here we
      have demonstrated genetically that the NTR of Msh6 has an important role in MMR
      that is partially redundant with PCNA binding. Small-angle X-ray scattering
      (SAXS) was used to determine the solution structure of the complex of PCNA with
      Msh2-Msh6 and with the isolated Msh6 NTR, revealing that the Msh6 NTR is a
      natively disordered domain that forms an extended tether between Msh6 and PCNA.
      Moreover, computational analysis of PCNA-interacting motifs in the S. cerevisiae
      proteome indicated that flexible linkers are a common theme for PCNA-interacting
      proteins that may serve to localize these binding partners without tightly
      restraining them to the immediate vicinity of PCNA.

PMID- 17531815
TI  - Structure of the human MutSalpha DNA lesion recognition complex.
AB  - Mismatch repair (MMR) ensures the fidelity of DNA replication, initiates the
      cellular response to certain classes of DNA damage, and has been implicated in
      the generation of immune diversity. Each of these functions depends on MutSalpha
      (MSH2*MSH6 heterodimer). Inactivation of this protein complex is responsible for
      tumor development in about half of known hereditary nonpolyposis colorectal
      cancer kindreds and also occurs in sporadic tumors in a variety of tissues. Here,
      we describe a series of crystal structures of human MutSalpha bound to different
      DNA substrates, each known to elicit one of the diverse biological responses of
      the MMR pathway. All lesions are recognized in a similar manner, indicating that
      diversity of MutSalpha-dependent responses to DNA lesions is generated in events
      downstream of this lesion recognition step. This study also allows rigorous
      mapping of cancer-causing mutations and furthermore suggests structural pathways
      for allosteric communication between different regions within the heterodimer.

PMID- 17531816
TI  - Functional separation of the requirements for establishment and maintenance of
      centromeric heterochromatin.
AB  - The establishment and maintenance of centromeric heterochromatin in fission yeast
      require the RITS complex. Comprised of centromeric siRNAs, the chromodomain
      protein Chp1, Argonaute (Ago1), and Tas3, RITS couples the cellular RNAi pathway
      with assembly of constitutive heterochromatin. However, the mechanisms governing
      RITS-dependent establishment versus maintenance of centromeric heterochromatin
      remain unresolved. Here, we report that a mutant Tas3 protein that cannot bind
      Ago1 supports the maintenance of centromeric heterochromatin but cannot mediate
      efficient de novo establishment from cells transiently depleted for the histone
      H3 lysine 9 methyltransferase Clr4. In contrast, centromeric heterochromatin
      efficiently assembles in mutant cells transiently depleted for dicer. This mutant
      therefore allows ordering of the events leading to establishment of centromeric
      heterochromatin and places lysine 9 methylation of histone H3 upstream of dicer
      function.

PMID- 17531817
TI  - Cathodic stripping voltammetric determination of As(III) with in situ plated
      bismuth-film electrode using the catalytic hydrogen wave.
AB  - A highly sensitive method has been developed for the determination of trace
      As(III) by a square wave cathodic stripping voltammetry employing in situ plated
      bismuth-film on edge-plane graphite substrate as working electrode. The presence
      of As(III) enhanced a cathodic peak corresponding to the catalytic hydrogen wave
      due to Se(IV) at about -1150 mV. Linear calibration curves for As(III)
      determination were obtained over the concentration ranges of 0.01-1.0 microg L(
      1) and 1.0-12.0 microg L(-1) at deposition times of 30 s and 10 s, respectively.
      The detection limit (3sigma) was estimated to be as low as 0.7 ng L(-1) As(III)
      at 30 s deposition time. The optimum experimental parameters and probable
      interference from foreign ions and organic compounds were investigated. This
      proposed method could be applied to analyses of certified reference material,
      synthetic and natural water samples.

PMID- 17531818
TI  - Total inorganic arsenic detection in real water samples using anodic stripping
      voltammetry and a gold-coated diamond thin-film electrode.
AB  - An accurate method for total inorganic arsenic determination in real water
      samples was developed using differential pulse anodic stripping voltammetry
      (DPASV) and a Au-coated boron-doped diamond thin-film electrode. Keys to the
      method are the use of a conducting diamond platform and solid phase extraction
      for sample preparation. In the method, the As(III) present in the sample is first
      detected by DPASV. The As(V) present is then reduced to As(III) by reaction with
      Na2SO3 and this is followed by a second detection of As(III) by DPASV.
      Interfering metal ions (e.g., Cu(II)) that cause decreased electrode response
      sensitivity for arsenic in real samples are removed by solid phase extraction as
      part of the sample preparation. For example, Cu(II) caused a 30% decrease in the
      As stripping peak current at a solution concentration ratio of 3:1
      (Cu(II)/As(III)). This loss was mitigated by passage of the solution through a
      Chelex 100 cation exchange resin. After passage, only a 5% As stripping current
      response loss was seen. The effect of organic matter on the Au-coated diamond
      electrode response for As(III) was also evaluated. Humic acid at a 5 ppm
      concentration caused only a 9% decrease in the As stripping peak charge for Au
      coated diamond. By comparison, a 50% response decrease was observed for Au foil.
      Clearly, the chemical properties of the diamond surface in the vicinity of the
      metal deposits inhibit molecular adsorption on at least some of the Au surface.
      The method provided reproducible and accurate results for total inorganic arsenic
      in two contaminated water samples provided by the U.S. Bureau of Reclamation. The
      total inorganic As concentration in the two samples, quantified by the standard
      addition method, was 23.2+/-2.9 ppb for UV plant influent water and 16.4+/-0.9
      ppb for Well 119 water (n=4). These values differed from the specified
      concentrations by less than 4%.

PMID- 17531819
TI  - Mesoporous tungsten titanate as matrix for matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry analysis of biomolecules.
AB  - In this paper, mesoporous tungsten titanate (WTiO) with different nano-pore
      structures was utilized as matrix for the analysis of short peptides by matrix
      assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI
      TOFMS). Effect of characteristic features of mesoporous matrices on laser
      desorption/ionization process was investigated. Experiments showed that the
      ordered two-dimensional and three-dimensional mesoporous matrices were superior
      in performance to the non-ordered WTiO matrix. The dramatic enhancement of signal
      sensitivity by the ordered mesoporous matrices can be reasonably attributed to
      the ordered structure, which facilitated the understanding on structure-function
      relationship in mesoporous cavity for laser desorption process of adsorbed
      biomolecules. With the ordered mesoporous matrix, the short peptides are
      successfully detected. The presence of trace alkali metal salt effectively
      increased the analyte ion yields and the MALDI-TOFMS using the inorganic
      mesoporous matrices displayed a high salt tolerance. The developed technique also
      showed a satisfactory performance in peptide-mapping and amino-acid sequencing
      analysis.

PMID- 17531820
TI  - Correlation between the synthetic origin of methamphetamine samples and their 15N
      and 13C stable isotope ratios.
AB  - The active ingredient of ecstasy, N-methyl-3,4-methyldioxyphenylisopropylamine
      (MDMA) can be manufactured by a number of easy routes from simple precursors. We
      have synthesised 45 samples of MDMA following the five most common routes using N
      precursors from 12 different origins and three different precursors for the
      aromatic moiety. The 13C and 15N contents of both the precursors and the MDMA
      samples derived therefrom were measured by isotope ratio mass spectrometry
      coupled to an elemental analyser (EA-IRMS). We show that within-pathway
      correlation between the 15N content of the precursor and that of the derived MDMA
      can be strong but that no general pattern of correlation can be defined. Rather,
      it is evident that the delta15N values of MDMA are strongly influenced by a
      combination of the delta15N values of the source of nitrogen used, the route by
      which the MDMA is synthesised, and the experimental conditions employed.
      Multivariate analysis (PCA) based on the delta15N values of the synthetic MDMA
      and of the delta15N and delta13C values of the N-precursors leads to good
      discrimination between the majority of the reaction conditions tested.

PMID- 17531821
TI  - Evaluation of nutritional parameters in infant formulas and powdered milk by
      Raman spectroscopy.
AB  - It has been made a critical evaluation of the application of near infrared
      Fourier transform-Raman spectroscopy for the simultaneous determination of the
      most important nutritional parameters such as energetic value, carbohydrate,
      protein and fat contents of infant formula and powdered milk samples based on the
      use of partial least squares (PLS) regression analysis. A highly heterogeneous
      population of 23 samples, covering a wide range of infant food formula and
      powdered milk, were obtained from the Spanish market. Raman spectra, obtained by
      excitation with a Nd:YAG laser at 1064 nm, show no disturbing fluorescence
      effects; therefore sample spectra can be recorded without any previous
      preparation step. After correcting the spectra, hierarchical cluster analysis was
      performed in order to select a representative calibration set and the
      corresponding validation sample set. Different PLS models and several spectral
      windows were tested in order to evaluate their prediction capabilities for the
      validation set. Considering a calibration set comprised of three replicate
      spectra of 15 samples and a validation data set of eight samples, the procedure
      developed provided figures of merit which complied with the statutory values
      declared by the United States Food and Drug Administration (US FDA).

PMID- 17531822
TI  - Monitoring of the smoking process by multicommutation Fourier transform infrared
      spectroscopy.
AB  - Nicotine was selected as the target molecule for monitoring of the smoking
      process by multicommutation Fourier Transform Infrared spectroscopy (FTIR). The
      method involved the use of CHCl3 for on-line extraction of nicotine from tobacco,
      cigarette filters and tobacco ash from NH4OH alkalinized samples, and absorbance
      measurement of the characteristic band at 1316 cm(-1) in the stopped-flow mode,
      by obtaining the peak area in the range between 1334 and 1300 cm(-1). Under the
      best operational conditions, the procedure developed provided a detection limit
      of 0.05 mg mL(-1) nicotine, corresponding to 0.5 mg g(-1) in the solid sample, a
      relative standard deviation less than 2.5%, and a sampling frequency of 12
      determinations h(-1). It can be concluded that nicotine migrates in the smoke
      mainstream towards the filter during the smoking process. The smoking of
      cigarettes and cigars is different. Nicotine is retained weakly by both tobacco
      and filter in the case of cigarettes, and strongly by the unburned tobacco in
      cigars. The incomplete smoking of cigars and cigarettes reduces nicotine intake
      and thus reduces the additive effect.

PMID- 17531823
TI  - Reliable and fast quantitative analysis of active ingredient in pharmaceutical
      suspension using Raman spectroscopy.
AB  - The concentration of acetaminophen in a turbid pharmaceutical suspension has been
      measured successfully using Raman spectroscopy. The spectrometer was equipped
      with a large spot probe which enabled the coverage of a representative area
      during sampling. This wide area illumination (WAI) scheme (coverage area 28.3
      mm2) for Raman data collection proved to be more reliable for the compositional
      determination of these pharmaceutical suspensions, especially when the samples
      were turbid. The reproducibility of measurement using the WAI scheme was compared
      to that of using a conventional small-spot scheme which employed a much smaller
      illumination area (about 100 microm spot size). A layer of isobutyric anhydride
      was placed in front of the sample vials to correct the variation in the Raman
      intensity due to the fluctuation of laser power. Corrections were accomplished
      using the isolated carbonyl band of isobutyric anhydride. The acetaminophen
      concentrations of prediction samples were accurately estimated using a partial
      least squares (PLS) calibration model. The prediction accuracy was maintained
      even with changes in laser power. It was noted that the prediction performance
      was somewhat degraded for turbid suspensions with high acetaminophen contents.
      When comparing the results of reproducibility obtained with the WAI scheme and
      those obtained using the conventional scheme, it was concluded that the
      quantitative determination of the active pharmaceutical ingredient (API) in
      turbid suspensions is much improved when employing a larger laser coverage area.
      This is presumably due to the improvement in representative sampling.

PMID- 17531824
TI  - Two-dimensional correlation spectroscopy and multivariate curve resolution for
      the study of lipid oxidation in edible oils monitored by FTIR and FT-Raman
      spectroscopy.
AB  - Accelerate oxidative degradation of six vegetable oils was monitored using FTIR
      and FT-Raman spectroscopy. Two-dimensional correlation spectroscopy and
      multivariate curve resolution alternating least squares (MCR-ALS) were applied to
      the analysis of the data. The use of hetero-spectral two-dimensional correlation
      of FTIR and FT-Raman data allowed the use of well established band assignments to
      interpret less clearly assigned spectral features. With a moving window approach
      it was possible to obtain simplified two-dimensional correlation maps and to
      detect compounds evolving with different kinetic. Simultaneous analysis of the
      oxidation experiments of the six different oils monitored by both spectroscopic
      techniques was performed using MCR-ALS. Although a complete resolution of the
      data was not possible, the spectral changes occurring during the oxidative
      degradation of the oils were described with a five-component model. The two
      fundamentally different chemometric approaches lead to coincident results.

PMID- 17531825
TI  - QSAR study of angiotensin II antagonists using robust boosting partial least
      squares regression.
AB  - In the current study, robust boosting partial least squares (RBPLS) regression
      has been proposed to model the activities of a series of 4H-1,2,4-triazoles as
      angiotensin II antagonists. RBPLS works by sequentially employing PLS method to
      the robustly reweighted versions of the training compounds, and then combing
      these resulting predictors through weighted median. In PLS modeling, an F
      statistic has been introduced to automatically determine the number of PLS
      components. The results obtained by RBPLS have been compared to those by boosting
      partial least squares (BPLS) repression and partial least squares (PLS)
      regression, showing the good performance of RBPLS in improving the QSAR modeling.
      In addition, the interaction of angiotensin II antagonists is a complex one,
      including topological, spatial, thermodynamic and electronic effects.

PMID- 17531826
TI  - Results from the "Technical workshop on genotoxicity biosensing" on the micro
      scale fluorometric assay of deoxyribonucleic acid unwinding.
AB  - The fluorometric analysis of DNA unwinding (FADU assay) was originally designed
      for rapid detection of X-ray-induced DNA damage in mammalian cells. This cellular
      bioassay is based on time-dependent alkaline denaturation of DNA under moderate
      denaturing conditions (pH 12.2-12.4) starting from ends as well as from all DNA
      break points (single-strand breaks, SSB; double-strand breaks, DSB; alkali-labile
      sites, ALS). DNA which remained double-stranded after 30 min of alkaline
      treatment was detected after neutralisation and immediate fragmentation followed
      by binding to the Hoechst 33258 dye (bisbenzimide) and fluorescence measures. In
      the current paper, a modified method was used which allows cell cultivation and
      chemical treatment in the same microplate (micro-FADU) followed by analysis of 96
      samples in a microplate fluorescence reader. Exposure of mammalian cells to
      chemicals was performed for 60 min on ice thus allowing identification of direct
      acting substances capable of inducing DNA-strand breaks. As an inter-assay
      standard the action of hydrogen peroxide was tested in every test plate. The
      results demonstrate that the micro-FADU assay is suitable to detect the presence
      of chemically induced strand breaks within 3 h.

PMID- 17531827
TI  - Selective detection of gas-phase TNT by integrated optical waveguide spectrometry
      using molecularly imprinted sol-gel sensing films.
AB  - A chemical sensor was developed to detect the explosive 2,4,6-trinitrotoluene
      (TNT) utilizing planar integrated optical waveguide (IOW) attenuated total
      reflection spectrometry. Submicron thick films of organically modified sol-gel
      polymers were deposited on the waveguide surface as the sensing layer. Sol-gels
      were molecularly imprinted for TNT using covalently bound template molecules
      linked to the matrix through 1 or 2 carbamate linkages. Upon chemical cleavage of
      the template and displacement of the TNT-like pendant groups from the matrix,
      shape-selective binding sites were created that possess a primary amine group.
      The amine was used to deprotonate bound TNT yielding an anionic form that absorbs
      visible light. Binding of TNT and subsequent conversion to the anion results in
      the attenuation of light propagating through the waveguide, thus creating a
      spectrophotometric device. Sensitivity can be achieved by taking advantage of the
      substantial pathlength provided by the use of single mode IOWs. The limit-of
      detection to gas-phase TNT was found to be five parts-per-billion (ppbV) in
      ambient air at a flow rate of 40 mL min(-1) given a 60 s sampling time. The
      sensor is highly selective for TNT due to the selectivity of binding site
      recognition of TNT and the subsequent generation of the TNT anion. Response to
      TNT is not reversible which results in an integrating sensor device which, in
      theory, can improve the ability to detect small amounts of the explosive if the
      exposure time is sufficient in length.

PMID- 17531828
TI  - Optimization of separation and detection of 6-aminoquinolyl derivatives of amino
      acids by using reversed-phase liquid chromatography with on line UV, fluorescence
      and electrochemical detection.
AB  - The combined use of UV-absorbance, fluorescence and electrochemical detection was
      proposed for the analysis of a set of thirteen amino acids by reversed-phase
      liquid chromatography (RP-HPLC) using 6-aminoquinolyl-N-hydroxysuccinimidyl
      carbamate as a precolumn derivatization reagent. The utility of using three
      detectors in series was demonstrated. The separation of all derivatized amino
      acids was optimized with the aid of a computer optimization program from only
      four simple linear gradient measurements. The effectiveness of a reliable
      retention prediction of solutes under any gradient profile using other gradient
      or isocratic data was also examined.

PMID- 17531829
TI  - Determination of synephrine in weight-loss products using high performance liquid
      chromatography with acidic potassium permanganate chemiluminescence detection.
AB  - Adrenergic amines found in extracts of Citrus aurantium (bitter orange) evoke
      analytically useful chemiluminescence with acidic potassium permanganate in the
      presence of polyphosphates. From corrected chemiluminescence spectra, the
      wavelength of maximum intensity for these reactions was 680+/-5 nm and, using
      flow injection analysis methodology, limits of detection for synephrine,
      octopamine, tyramine and hordenine were found to be between 1x10(-9) and 1x10(-8)
      M. We have applied this method of detection to the rapid determination of
      synephrine in dietary supplements using monolithic column chromatography.

PMID- 17531830
TI  - Different radical scavenging tests in virgin olive oil and their relation to the
      total phenol content.
AB  - Four different antioxidant tests (ABTS*+, DPPH, ORAC, beta-carotene-linoleate
      model system) were used to determine the free-radical scavenging activity of 39
      extra virgin olive oils (EVOO) and compare the total phenol content by the Folin
      Ciocalteu method. The correlation between the total phenols and antioxidant
      capacities measured by the four methods was very high, and highest with ABTS*+
      (R2 = 0.9905). Some of these methods of measurement were applied to olive-oil
      samples (OO), with approximately a 50% decrease in the value of the antioxidant
      capacity in comparison with values found for EVOO. In conclusion, the results
      show that all the methods tested were suitable for determining the antioxidant
      capacity of olive oil. The Picual variety of extra-virgin olive oil showed high
      antioxidant activity.

PMID- 17531831
TI  - Assessing air quality inside vehicles and at filling stations by monitoring
      benzene, toluene, ethylbenzene and xylenes with the use of semipermeable devices.
AB  - BTEX (benzene, toluene, ethylbenzene, and xylenes) were used as target molecules
      to evaluate the quality of air inside motor vehicles and near filling stations,
      using semipermeable membrane devices (SPMDs) as low-cost passive sampling
      devices. A direct, fast, simple methodology based on the use of headspace-gas
      chromatography-mass spectrometry detection (HS-GC-MS) was developed for BTEX
      determinations, without any sample pre-treatment. SPMDs (25.4 cm2 surface, filled
      with 100 microL triolein) were employed as static samplers. After the selected
      deployment time, the SPMDs were heated inside a HS vial at 150 degrees C for 20
      min and BTEX compounds were determined by GC-MS in selected ion monitoring (SIM)
      mode in less than 12 min. The proposed method provides limits of detection of
      less than 1 ng SPMD(-1) for all compounds studied; which is equivalent to 0.3-8
      ng m(-3) in air for a deployment time of 24 h, and to 9-200 microg m(-3) for 10
      min time, as a function of the compound considered. Using sampling times of
      around 24 h, concentrations from 0.2 to 145 microg m(-3) were measured inside
      motor vehicles. For exposure times from 2 to 40 min, concentrations of BTEX
      ranging from 0.03 to 79 mg m(-3) were measured at filling stations, especially
      during refueling of vehicles with gasoline.

PMID- 17531832
TI  - Electrostatic accumulation and determination of triclosan in ultrathin carbon
      nanoparticle composite film electrodes.
AB  - A film composed of carbon nanoparticles and poly(diallyldimethylammonium
      chloride) or CNP-PDDAC is formed in a layer-by-layer deposition process at tin
      doped indium oxide (ITO) substrates. Excess positive binding sites within this
      film in aqueous phosphate buffer at pH 9.5 are quantified by adsorption of
      iron(III)phthalocyanine tetrasulfonate and indigo carmine. Both anionic redox
      systems bind with Langmuirian characteristics (K approximately 10(5) mol(-1) dm3)
      and show electrochemical reactivity throughout the film at different thicknesses.
      Therefore, the electrical conductivity in CNP-PDDAC films is good and the
      positive binding sites are approximately 140 pmol cm(-2) per layer. Structural
      instability of the CNP-PDDAC film in the presence of high concentrations of
      iron(III)phthalocyanine tetrasulfonate or indigo carmine is observed. Triclosan,
      a widely used anti-bacterial and anti-fungal agent, exists in aqueous media at pH
      9.5 as a negatively charged chlorinated poly-aromatic phenol. Due to the negative
      charge, triclosan is readily accumulated into CNP-PDDAC films with an efficiency
      consistent with that expected for simple electrostatic interaction with the
      cationic binding sites. Oxidation of bound triclosan occurs at 0.6 V versus SCE
      in a chemically irreversible process. The CNP-PDDAC film electrode is renewed by
      rinsing in organic solvent and the triclosan oxidation response is shown to
      correlate with the triclosan concentration in solution from 0.5 to 50 microM.
      Applications of the CNP-PDDAC film electrode (or improved versions of it) in
      analysis or in anodic extraction are proposed.

PMID- 17531833
TI  - Selective solid-phase extraction of trace cadmium(II) with an ionic imprinted
      polymer prepared from a dual-ligand monomer.
AB  - A novel dual-ligand reagent (2Z)-N,N'-bis(2-aminoethylic)but-2-enediamide, was
      synthesized and applied to prepare metal ion-imprinted polymers (IIPs) materials
      by ionic imprinted technique for selective solid-phase extraction (SPE) of trace
      Cd(II) from aqueous solution. In the first step, Cd(II) formed coordination
      linkage with the two ethylenediamine groups of the synthetic monomer. Then the
      complex was copolymerized with pentaerythritol triacrylate (crosslinker) in the
      presence of 2,2'-azobisisobutyronitrile as initiator. Subsequently, the imprinted
      Cd(II) was completely removed by leaching the dried and powdered materials
      particles with 0.5 M HCl. The obtained IIPs particles exhibited excellent
      selectivity for target ion. The distribution ratio (D) values of Cd(II)-IIPs for
      Cd(II) were greatly larger than that for Cu(II), Zn(II) and Hg(II). The relative
      selective factor (alpha(r)) values of Cd(II)/Cu(II), Cd(II)/Zn(II) and
      Cd(II)/Hg(II) were 25.5, 35.3 and 62.1. The maximum static adsorption capacity of
      the ion-imprinted and non-imprinted sorbent for Cd(II) was 32.56 and 6.30 mg g(
      1), respectively. Moreover, the times of adsorption equilibration and complete
      desorption were remarkably short. The prepared Cd(II)-IIPs were shown to be
      promising for solid-phase extraction coupled with inductively coupled plasma
      atomic emission spectrometry (ICP-AES) for the determination of trace Cd(II) in
      real samples. The precision (R.S.D.) and detection limit (3sigma) of the method
      were 2.4% and 0.14 microg L(-1), respectively. The column packed with Cd(II)-IIPs
      was good enough for Cd(II) separation in matrixes containing components with
      similar chemical behaviour such as Cu(II), Zn(II) and Hg(II).

PMID- 17531835
TI  - The destructive alliance: interactions of leukocytes, cerebral endothelial cells,
      and the immune cascade in pathogenesis of multiple sclerosis.
AB  - Multiple sclerosis (MS) is an inflammatory disease of the human central nervous
      system (CNS) which develops predominantly in young adults with certain
      predisposing genetic characteristics, often following exposure to initiating
      environmental insult(s) including viral infections. The causes of MS remain
      elusive and no entire cure is in sight. However, it is well known that
      interactions between the immune system and the CNS play a central role in MS
      pathogenesis. Patients with MS generate CD4+ autoreactive T cells that at some
      point differentiate to Th1 phenotype cells, which are the major players in
      maintaining a continuous destructive immune response against brain and spinal
      cord antigens. Other significant participants in MS pathogenesis involved in the
      destruction of the target tissue are cerebral endothelial cells, CD8+ T cells, B
      cells, complement, autoantibodies, cytokines, and chemokines. The presence and
      interactions of all these participants further complicate the pathogenesis of MS,
      and make finding a cure for MS challenging. This chapter looks at the roles of
      these factors in the development of MS.

PMID- 17531836
TI  - Role of B cells in pathogenesis of multiple sclerosis.
AB  - Despite the current limited understanding of the etiology of multiple sclerosis
      (MS), genetic susceptibility and environmental influences are known driving
      factors. MS is considered a T-cell-mediated disease given the prevalence of T
      cells in plaques. Plaque formation is characteristic of this disease attributable
      to immune mechanisms, triggered by an autoimmune attack aimed at antigens in the
      myelin sheath or oligodendrocyte proteins. The attack consists of the following:
      The role of the B cells is twofold: first, as autoreactive B cells they produce
      autoantibodies, secrete cytokines, clonally replicate memory B cells, and long
      living plasma cells which serve to advance the diseased state by their constant
      production of autoantibodies. Second, as antigen-presenting cells they activate
      the autoreactive T cells. For this reason, the stipulation that T cell is the
      cornerstone of MS must be reevaluated. Various studies on pathogenesis of MS have
      indicated that B cells, as the humoral component of the adaptive immune system,
      are active participants in pathogenesis and lesion maintenance throughout the
      disease process. The active role of B cells and autoantibodies makes them an
      encouraging therapeutic target. Advances in the understanding of B-cell
      development and activity would allow for an enhanced strategy in the design of
      autoimmune treatment. For this reason, further investigation is necessary to
      determine whether depletion of B cells or antibodies may restore immune function.

PMID- 17531837
TI  - The role of CD4 T cells in the pathogenesis of multiple sclerosis.
AB  - T lymphocytes play a central role in the pathogenesis of multiple sclerosis (MS)
      (Zhang et al., 1992). Both CD4+ and CD8+ T cells have been demonstrated in MS
      lesions, with CD4+ T cells predominating in acute lesions and CD8+ T cells being
      observed more frequently in chronic lesions (Raine, 1994). Additionally, T cells
      are found in all four of the described histopathologic subtypes of MS
      (Lucchinetti et al., 2000). Activated myelin-reactive CD4+ T cells are present in
      the blood and cerebrospinal fluid (CSF) of MS patients; in contrast, only
      nonactivated myelin-reactive T cells are present in the blood of controls (Zhang
      et al., 1994). The success of several T-cell-targeted therapies in MS reinforces
      the importance of the role of the T cell in MS pathogenesis. Here, we outline
      basic concepts in CD4+ T-cell immunology and summarize the current understanding
      of the role of CD4+ T cells in the pathogenesis of MS.

PMID- 17531838
TI  - The CD8 T cell in multiple sclerosis: suppressor cell or mediator of
      neuropathology?
AB  - Multiple sclerosis (MS) is the most common human demyelinating disease of the
      central nervous system. It is universally accepted that the immune system plays a
      major role in the pathogenesis of MS. For decades, CD4 T cells have been
      considered the predominant mediator of neuropathology in MS. This perception was
      largely due to the similarity between MS and CD4 T-cell-driven experimental
      allergic encephalomyelitis, the most commonly studied murine model of MS. Over
      the last decade, several new observations in MS research imply an emerging role
      for CD8 T cells in neuropathogenesis. In certain experimental autoimmune
      encephalomyelitis (EAE) models, CD8 T cells are considered suppressors of
      pathology, whereas in other EAE models, neuropathology can be exacerbated by
      adoptive transfer of CD8 T cells. Studies using the Theiler's murine
      encephalomyelitis virus (TMEV) model have demonstrated preservation of motor
      function and axonal integrity in animals deficient in CD8 T cells or their
      effector molecules. CD8 T cells have also been demonstrated to be important
      regulators of blood-brain barrier permeability. There is also an emerging role
      for CD8 T cells in human MS. Human genetic studies reveal an important role for
      HLA class I molecules in MS susceptibility. In addition, neuropathologic studies
      demonstrate that CD8 T cells are the most numerous inflammatory infiltrate in MS
      lesions at all stages of lesion development. CD8 T cells are also capable of
      damaging neurons and axons in vitro. In this chapter, we discuss the
      neuropathologic, genetic, and experimental evidence for a critical role of CD8 T
      cells in the pathogenesis of MS and its most frequently studied animal models. We
      also highlight important new avenues for future research.

PMID- 17531839
TI  - Immunopathogenesis of multiple sclerosis.
AB  - Multiple sclerosis (MS) is considered an immune-mediated disorder in which immune
      cells cross the blood-brain barrier to enter the central nervous system (CNS)
      wherein they augment the neuropathology of the disease. This chapter discusses
      the role of various immune cell types that contribute to the development and
      progression of MS. Specifically, the role of T cells, antigen-presenting cells,
      and components of the innate immune system such as macrophages, B cells, and the
      complement system are discussed. The involvement of CNS-specific cells such as
      microglia, astrocytes, and neurons in MS are discussed and the immunosuppressive
      role of regulatory T cells is considered. We introduce the involvement of
      chemokines and matrix metalloproteinases which helps recruit immune cells into
      the CNS in MS. Although the causes of MS are unknown, various factors such as
      genetic influences, environmental effects, and involvement of infectious agents
      as potential contributors to MS immune dysfunctions are also considered. With
      this background, we discuss the mechanisms of the immunomodulators that are used
      to treat MS.

PMID- 17531840
TI  - Molecular mimicry in multiple sclerosis.
AB  - One of the most common demyelinating central nervous system (CNS) diseases in
      humans is multiple sclerosis (MS). The disease can be very debilitating with
      vision loss, motor and sensory disturbances, and cognitive impairment. The
      clinical course may present as a relapsing-remitting disease course, a
      progressive disease course, or a combination thereof. The etiology of MS is
      unknown. Though many viruses have been shown to be associated with MS, no one
      virus has ever been demonstrated to be the cause of MS. In addition, MS is
      thought to have an autoimmune component. Molecular mimicry is one hypothesis put
      forth which could reconcile the diverse pathology and etiology of MS. Molecular
      mimicry occurs when peptides from pathogens share sequence or structural
      similarities with self-antigens. Infection with various pathogens, each with its
      individual molecular mimic to a CNS antigen, may explain the inability of
      investigators to link one specific virus to MS. Molecular mimicry may be mediated
      through human leukocyte antigen class I- and class II-restricted T cells and
      antibodies, which may explain the diversity in phenotype. Aspects of molecular
      mimicry will be discussed in relation to each of these immune system components.
      Examples of various molecular mimics will be discussed with a particular focus on
      the CNS and MS. Molecular mimicry alone may not be able to induce disease;
      priming of the immune system by infection with a pathogen that carries a
      molecular mimic to self may have to be followed by a later nonspecific
      immunologic challenge in order for disease to be initiated. Recent research into
      this priming and triggering of disease will be discussed in relation to an animal
      model for MS.

PMID- 17531841
TI  - Molecular "negativity" may underlie multiple sclerosis: role of the myelin basic
      protein family in the pathogenesis of MS.
AB  - Myelin basic protein (MBP) binds to negatively charged lipids on the cytosolic
      surface of oligodendrocyte membranes and is responsible for adhesion of these
      surfaces in the multilayered myelin sheath. The pattern of extensive
      posttranslational modifications of MBP is dynamic during normal central nervous
      system development and during myelin degeneration in multiple sclerosis (MS),
      affecting its interactions with the myelin membranes and other proteins. In
      particular, the degree of deimination (or citrullination) of MBP is correlated
      with the severity of MS, and may represent a primary defect that precedes
      neurodegeneration due to autoimmune attack. That MBP deimination also affects
      topological accessibility of an otherwise partially buried immunodominant epitope
      of the protein indicates that this modification may play a major role in the
      autoimmune pathogenesis of the disease. In this chapter, we describe the
      structural and functional consequences of MBP deimination in healthy and diseased
      myelin.

PMID- 17531842
TI  - Microchimerism and stem cell transplantation in multiple sclerosis.
AB  - Scientific advances have demonstrated that autoreactive cells are a component of
      the healthy immune repertoire. If we define autoimmunity as an active induction
      of autoreaction, the solution should be an active induction of self-tolerance,
      and may indicate the direction to explore the future therapies. Microchimerism
      (MC) refers to the presence of a limited number of nonhost cells in the body of
      an individual. These cells can enter via blood transfusion and organ
      transplantation or naturally through pregnancy. Chimeric cells engraft in the
      host body, develop, proliferate, and are accepted by the immune system as self.
      These include stem cells that enter the maternal body during fetal stages. These
      stem cells are also postulated to be helpful reservoirs in protecting the host
      body. MC has been considered a risk factor in autoimmune disease induction.
      However, today we know it is a natural phenomenon. MC can be considered a natural
      model of successful transplantation, the earliest engrafting cells being fetal
      mesenchymal stem cells (MSCs). MSCs have two notable features. They have an
      immunosuppressive quality when encountering the adoptive immune system and they
      display repair-inducing potential within damaged tissues. For the fetus, MC
      appears to be an effective factor in maternal tolerance induction toward the
      fetal graft and for the mother; these novel fetal cells might be useful in
      disease conditions occurring after pregnancy. Hematopoietic stem cell
      transplantation has become an accepted treatment option for both malignant and
      nonmalignant diseases and this unique procedure is now being investigated as a
      potential therapy for multiple sclerosis (MS). Due to the dichotomous properties
      of MSC, suppressing aggressive immune dysfunction while promoting damaged tissue
      repair, they may be appropriate therapy for MS.

PMID- 17531843
TI  - The insulin-like growth factor system in multiple sclerosis.
AB  - Multiple sclerosis (MS) is a chronic disorder of the central nervous system
      characterized by inflammation, demyelination, and axonal degeneration. Present
      therapeutic strategies for MS reduce inflammation and its destructive
      consequences, but are not effective in the progressive phase of the disease.
      There is a need for neuroprotective and restorative therapies in MS. Insulin-like
      growth factor-1 (IGF-1) is of considerable interest because it is not only a
      potent neuroprotective trophic factor but also a survival factor for cells of the
      oligodendrocyte lineage and possesses a potent myelinogenic capacity. However,
      the IGF system is complex and includes not only IGF-1 and IGF-2 and their
      receptors but also modulating IGF-binding proteins (IGFBPs), of which six have
      been identified. This chapter provides an overview of the role of the IGF system
      in the pathophysiology of MS, relevant findings in preclinical models, and
      discusses the possible use of IGF-1 as a therapeutic agent for MS.

PMID- 17531844
TI  - Cell-derived microparticles and exosomes in neuroinflammatory disorders.
AB  - All blood cells and the vascular endothelium shed microparticles (MP) from their
      plasma membranes when suitably stimulated, and assay of MP in patient blood has
      found increasing application to the monitoring of disease states. In addition,
      mounting evidence suggests that MP are not mere epiphenomena but play significant
      roles in the pathophysiology of thromboses, inflammation, and cancers. This
      chapter endeavors to summarize the limited number of studies thus far done on MP
      in neurological disorders such as multiple sclerosis (MS), transient ischemic
      attacks, and the neurological manifestations of antiphospholipid syndrome (APS).
      In addition, the chapter offers some plausible hypotheses on possible roles of MP
      in the pathophsyiology of these disorders, chiefly, the hypothesis that MP are
      indeed important participants in some neuropathologies, especially those which
      are ischemic in nature, but probably also inflammatory ones. The chapter also
      goes over the history and general principles of MP studies (e.g., assay methods
      and pitfalls), comparison with alternative methods (e.g., soluble markers of
      disease states), subclasses of MP (such as exosomes), and other topics aimed at
      helping readers to consider MP studies in their own clinical fields. Tables
      include a listing of bioactive agents known to be carried on MP, many of which
      were heretofore considered strictly soluble, and some of which can be transferred
      from cell to cell via MP vectors, for example certain cytokine receptors.

PMID- 17531845
TI  - Multiple sclerosis in children: clinical, diagnostic, and therapeutic aspects.
AB  - Multiple sclerosis (MS) is the most common inflammatory disease of human central
      nervous system (CNS), which is characterized by inflammatory demyelination and
      neuroaxonal injury/loss. The majority of MS patients are diagnosed in early- to
      mid-adulthood; however, the onset of MS in childhood is being increasingly
      recognized. Although adults and children share important aspects of the disease,
      several features including course of the disease and a broader differential
      diagnosis are unique to children. This chapter summarizes recent insights and
      emphasizes that children with MS should be started on immunomodulatory therapies
      early in order to prevent future disability.

PMID- 17531846
TI  - Migraine in multiple sclerosis.
AB  - Headache and migraine are common features in multiple sclerosis (MS) and can
      influence the diagnosis, radiological evaluation, treatment, and quality of life
      of these patients. Similarities in symptoms between patients with migraine and MS
      presenting with headache can lead to misdiagnosis. Likewise, MRI lesions which
      may be found in migraine patients without other neurological symptoms or signs
      may cause diagnostic confusion and patient anxiety. Studies addressing the
      pathophysiology of these comorbid conditions have not found a clear link, but
      brainstem lesions and inflammatory processes have been proposed. Management of de
      novo or treatment-induced headache in the MS patient is fairly straightforward if
      the physician is aware of the problem.

PMID- 17531847
TI  - Multiple sclerosis as a painful disease.
AB  - Pain is a common problem of patients with multiple sclerosis (MS) and may be due
      to central/neuropathic or peripheral/somatic pathology. Rarely MS may present
      with pain, or pain may herald an MS exacerbation, such as in painful tonic spasms
      or Lhermitte's sign. In other patients, pain may become chronic as a long-term
      sequela of damage to nerve root entry zones (trigeminal neuralgia) or structures
      in central sensory pathways. Migraine headache may develop as a consequence of
      MS, and headache can also be a side effect of interferon treatment. The
      pathophysiology of pain in MS may be linked to certain plaque locations which
      disrupt the spinothalamic and quintothalamic pathways, abnormal impulses through
      motor axons, development of an acquired channelopathy in affected nerves, or
      involve glial cell inflammatory immune mechanisms. At this time, the treatment of
      pain in MS employs the use of antiepileptic drugs, muscle relaxers/antispasmodic
      agents, anti-inflammatory drugs, and nonpharmacological measures. Research
      concerning cannabis-based treatments shows promising results, and substances
      which block microglial or astrocytic involvement in pain processing are also
      under investigation.

PMID- 17531848
TI  - Multiple sclerosis and behavior.
AB  - Multiple sclerosis (MS) is one of the most frequently seen neurological causes of
      progressive disability in early to middle adulthood. The disease is variable in
      its presentation and course, affects roughly 100-300 per 100,000 persons within
      the United States alone, and is slightly more common among females than males. MS
      places substantial burdens on patients, families, and caregivers. It negatively
      affects cognitive abilities and psychiatric functioning, and can add a notably
      deleterious effect on a patient's quality of life. This chapter reviews the
      recent literature on the behavioral manifestations of MS. Cognitive domains
      discussed include executive functioning, processing speed, attention, learning
      and memory, language functioning, and visual spatial processing. Some attention
      will also be paid to differential diagnosis and the cognitive effects of
      treatment. Psychiatric manifestations are also discussed, including symptoms of
      depression, bipolar disorder, euphoria, pathological laughter and crying, and
      psychosis, as well as maladaptive personality traits. Finally, the chapter
      concludes with a discussion of the effects of MS on quality of life including
      such areas as fatigue, sexual dysfunction, pain, employment, and cognitive
      functioning.

PMID- 17531849
TI  - Cerebrospinal fluid analysis in multiple sclerosis.
AB  - Although the diagnosis of multiple sclerosis (MS) may be clinically suspect and
      the magnetic resonance imaging findings compatible, cerebrospinal fluid (CSF)
      analysis remains mandatory in order to support the diagnosis. This is especially
      important since our understanding of the defining disease pathogenesis remains
      incomplete. However, there is no specifically diagnostic CSF test. And until
      recently, laboratory techniques for CSF analysis had not been rigorously
      standardized. Unconcentrated CSF without fixative should be used for the
      determinations of cell count and differential, protein and glucose, lactate,
      myelin basic protein, and the CSF/serum albumin ratio which is an indicator of
      blood-CSF barrier disruption. Additionally, CSF immunoglobulin-gamma (IgG)
      determinations are of major importance and are now included in the MS diagnostic
      criteria. Testing for oligoclonal IgG bands utilizing isoelectric focusing with
      IgG immunoblotting, the IgG synthesis rate, and the IgG index should be included.
      CSF analysis for kappa light chains and IGM may be diagnostically helpful. The
      search for biomarkers including those possibly present in the CSF which could
      predict and assess the course as well as response to treatment in a particular MS
      patient has not yet been successful. CSF immunoglobulin and T-cell/B-cell
      patterns, soluble HLA class I and II antigens, nitrous oxide metabolites,
      neurofilament and microtubule components and antibodies, tau protein, 14-3-3
      protein, neuronal cell and intercellular adhesion molecules, and chemokines are
      actively being investigated as MS biomarkers.

PMID- 17531850
TI  - Multiple sclerosis in Isfahan, Iran.
AB  - BACKGROUND: This survey was planned to study the prevalence and incidence of
      multiple sclerosis (MS) in Isfahan, Iran and to describe the clinical features of
      MS in general and in specific subgroups of patients (early-onset, late-onset,
      familial, and conjugal cases) and to compare our results with other reports.
      METHODS: A cross-sectional study was conducted from April 5, 2003 to July 31,
      2006. All patients known to have definite MS according to McDonald's criteria,
      alive, resident within Isfahan (a large province of Iran) and members of Isfahan
      MS Society (IMSS) were included in the study. Demographic and case-related
      information were recorded. A total number of 1718 definite MS patients (388 men
      and 1330 women) were identified from IMSS database. RESULTS: The overall period
      prevalence of MS was 43.8/100,000. Among men the prevalence was 19.2 (95% CI:
      17.4-21.2)/100,000 and among women 69.6 (95% CI: 66-73.4)/100,000. A female
      preponderance of 3.4 existed among these patients. In the year 2005, 143 new
      cases were diagnosed, resulting in an incidence rate of 3.64/100,000. The mean
      age of onset was 25.36 +/- 8.6 years (range 5-63 year), and mean duration of
      disease was 7.1 (+/-5.2) years for men and 6.7 (+/-5) years for women. Sensory
      and visual disturbances were the most common initial presentations with a
      prevalence of 51.7% and 47.5%, respectively. Cases identified include: early
      onset MS (less than 15 years old at onset) with 87 cases (5%), late-onset MS
      (over 50 years old at onset) with 20 cases (1.1%), familial MS with 209 cases
      (12.2%), and conjugal MS with 6 cases (0.5%). CONCLUSION: Isfahan is a medium- to
      high-risk area for MS, with prevalence higher than what has previously been
      reported, possibly because of an increase in the incidence rate. Clinical and
      demographic characteristics were similar to other reports; however, some
      differences existed.

PMID- 17531851
TI  - Gender issues in multiple sclerosis.
AB  - Multiple sclerosis (MS) varies considerably in the way that it affects females
      and males. The prevalence of the disease is much greater in women and tends to
      follow a different clinical course than it follows in the affected male
      population. It is also well known that MS symptoms often are much less of a
      problem during pregnancy. This chapter discusses possible explanations for gender
      differences based on sex hormones as well as the effects of these hormones on
      cytokines and other factors that may influence the course of MS. Knowledge of
      these effects may hold some promise in other types of treatment for MS. Since MS
      is much more prevalent in women of child-bearing age, there are also implications
      for the use of disease-modifying agents as well as drugs and treatments that may
      be useful for treatment of MS. MS often causes symptoms of sexual dysfunction,
      but there may be effective treatment for many of these treatments.

PMID- 17531852
TI  - Differential diagnosis of multiple sclerosis.
AB  - There are a number of illnesses that can mimic multiple sclerosis (MS). This
      pretty much includes any pathological process that can reflect injury to the
      central nervous system either in a transient or progressive basis. Typically, MS
      presents itself in individuals in their teens up to their late 30s. On occasion,
      however, one can see MS present in patients in their 60s. However, in retrospect,
      many of these patients might have had subtle manifestations of MS in their
      younger years. Visual obscuration or visual loss can be a manifestation of
      retinal ischemia, retinal migraine, or optic neuritis which might or might not
      evolve into a clinical picture compatible with MS. Cranial neuropathy, long tract
      signs, sensory disturbance, and/or gait ataxia can be related to a number of
      different processes such as illicit drug use, neurosarcoidosis, neuro-Behcet's
      disease, neuroborreliosis, HIV-related disease, neurosyphilis, vascular occlusive
      disease including vasculitis, connective tissue disorders, acute disseminated
      encephalomyelitis (ADEM), idiopathic transverse myelitis, neuromyelitis optica
      (NMO), or tropical spastic paraparesis. In addition, a constellation of symptoms,
      with questionable objective findings, along with normal MRI imaging, normal CSF
      results, and normal evoked response testing, when indicated, might identify a
      conversion disorder or possibly malingering. There are now established criteria
      for the diagnosis of MS, but initial presentations can be less than "textbook" in
      nature. With the advent of immunomodulating therapy, it has become more important
      to diagnose MS more effectively earlier on in the course of the illness. Prior to
      specific therapy for MS, astute clinicians did not necessarily move with alacrity
      to establish the diagnosis in patients with subtle or transient manifestations.
      This was in recognition of the fact that little could be offered to alter the
      course of the illness and a number of patients might never experience further
      problems if they were lucky enough to have their illness go into permanent
      remission after one minor exacerbation.

PMID- 17531853
TI  - Prognostic factors in multiple sclerosis.
AB  - Prognostic factors to determine the patient's likelihood of developing MS are
      important for several reasons. Prognostic factors are important to the patient
      who wants to be informed about his/her prospects, to the clinician who needs to
      individuate the patients who deserve immune treatments, and to the researcher who
      needs to improve the design and the analysis of the therapeutic trials. In
      addition, with the development of new immune therapies, whose early use is
      strongly encouraged, it is crucial to dispose of reliable clinical predictors to
      identify the patients who are candidates for early or aggressive therapies.
      Several studies have indicated that a poor prognosis is related to male gender; a
      late age at onset; motor, cerebellar, and sphincter involvement at onset; a
      progressive course at onset; a short inter-attack interval; a high number of
      early attacks; and a relevant early residual disability. Paraclinical support for
      MS prognosis is given by imaging techniques, cerebrospinal fluid analysis, and
      evoked potential examinations. The most sensitive paraclinical test to predict
      conversion from suspected demyelinating disease to definite MS is MRI.

PMID- 17531854
TI  - Neuroimaging in multiple sclerosis.
AB  - Conventional magnetic resonance imaging (MRI) has routinely been used to improve
      the accuracy of multiple sclerosis (MS) diagnosis and prognosis. Metrics derived
      from conventional MRI are now routinely used to detect therapeutic effects and
      extend clinical observations. However, conventional MRI measures, such as the use
      of lesion volume and count of gadolinium-enhancing and T2 lesions, have
      insufficient sensitivity and specificity to reveal the true degree of
      pathological changes occurring in MS. They cannot distinguish between
      inflammation, edema, demyelination, Wallerian degeneration, and axonal loss. In
      addition, they do not show a reliable correlation with clinical measures of
      disability and do not provide a complete assessment of therapeutic outcomes.
      Recent neuropathologic studies of typical chronic MS brains reveal macroscopic
      demyelination in cortical and deep gray matter (GM) that cannot be detected by
      currently available MRI techniques. Therefore, there is a pressing need for the
      development of newer MRI techniques to detect these lesions. Newer metrics of MRI
      analysis, including T1-weighted hypointense lesions, central nervous system
      atrophy measures, magnetization transfer imaging, magnetic resonance
      spectroscopy, and diffusion tensor imaging, are able to capture a more global
      picture of the range of tissue alterations caused by inflammation and
      neurodegeneration. At this time, they provide the only proof--albeit indirect-
      that important occult pathology is occurring in the GM. However, evidence is
      increasing that these nonconventional MRI measures correlate better with both
      existing and developing neurological impairment and disability when compared to
      conventional metrics.

PMID- 17531855
TI  - Detection of cortical lesions is dependent on choice of slice thickness in
      patients with multiple sclerosis.
AB  - Understanding the importance of cortical lesions in MS pathogenesis has changed.
      Histopathologic studies using new immunohistochemical methods show that cortical
      lesions can be detected more frequently than previously reported. Newer MRI
      sequences also detect cortical lesions more accurately. The aim of this study was
      to evaluate whether the effect of slice thickness (th) is an important factor for
      detection of cortical lesions in patients with multiple sclerosis (MS). We aimed
      also to investigate the relationship of cortical lesions with clinical status or
      other MRI variables. Forty-one patients with relapsing-remitting (RR) MS (11
      males, 30 females with mean EDSS 2.3) underwent scans of Two-dimensional (2D)
      fluid-attenuated inversion recovery (FLAIR) and 3D-T1-WI at 1.5-, 3-, and 5-mm
      slice thicknesses on 1.5-T MRI. Cortical and juxtacortical lesions were
      volumetrically assessed using a semiautomated method. 2D-FLAIR and 3D-T1-WI were
      coregistered and the matrix of the neocortical volume (NCV) segmentation mask
      (SIENAX-generated) was used to classify the location of the cortical-subcortical
      lesions. Cortical lesions fell into three classes: (1) class 1 were defined as
      lesions located in the NCV, (2) class 2 were juxtacortical lesions in contact
      with the NCV mask, and (3) class 3 were cortical-juxtacortical lesions situated
      in both regions. We measured NCV and normalized gray matter (GM) volume as well.
      We used partial correlation and multiple regressions to investigate the
      relationship between cortical lesions and other clinical and MRI variables. Of
      the total T2-lesion volume (T2-LV) measured on 1.5-mm th scans (mean 16108
      mm(3)), cortical lesions represented 2.4% (276 mm(3)), juxtacortical lesions 6.1%
      (760 mm(3)), and cortical-juxtacortical 3.7% (491 mm(3)). Compared to 1.5-mm th
      scan, cortical LV was reduced by -28.3%, p < 0.001 on 3-mm th and by -40.78%, p <
      0.001 on 5-mm th scans. Results for juxtacortical LV were for 3-mm th scans (
      17.9%, p < 0.01) and for 5-mm th scans (-30.3%, p < 0.01). The figures for
      cortical-juxtacortical LV were also for 3-mm th scans (-16.2%, p < 0.01) and for
      5-mm th scans (-26.7%, p < 0.01). We observed a significant correlation between
      T2-LV and GM atrophy in all slice thickness (r = -0.4 to -0.48, p = 0.001-0.003)
      and a modest relationship between cortical and cortical-juxtacortical LVs and
      disability, especially at 1.5-mm slice thickness (r = 0.35, p = 0.025). Use of
      thinner slices (1.5 mm) on 2D-FLAIR images can significantly increase the
      sensitivity and precision of detecting cortical and juxtracotical lesions in
      patients with MS. Cortical and juxtacortical lesions contribute more to
      disability development than total T2-LV alone.

PMID- 17531856
TI  - The role of quantitative neuroimaging indices in the differentiation of ischemia
      from demyelination: an analytical study with case presentation.
AB  - BACKGROUND AND PURPOSE: Differentiation of acute and subacute ischemic stroke
      lesions from acute demyelinating lesions of multiple sclerosis (MS) may not be
      possible on conventional magnetic resonance imaging (MRI). Both lesion types
      enhance on T1 with gadolinium (Gd) contrast and both are hyperintense on
      diffusion-weighted imaging (DWI). This study is an analysis of two quantitative
      MR indices: (1) calculated apparent diffusion coefficients (ADCs) and (2) T2
      relaxation times (T2R) as means toward differentiating acute ischemic lesions
      from acute demyelinating lesions. Chronic ischemic and demyelinating lesions were
      evaluated for comparison as well. METHODS: The MRI of nine patients with both
      acute and chronic ischemic lesions and six patients with both acute and chronic
      demyelinating lesions were analyzed for ADC and T2Rs. The indices were measured
      by manually placing regions of interest (ROIs) at the anatomic center of the
      acute lesion. Acute ischemic lesions were chosen by their hyperintensity on DWI
      and hypointensity on ADC mapping. Acute demyelinating lesions were selected by
      peripheral contrast enhancement after the administration of Gd. Computation of
      the ADC involved the diffusion coefficient on a region by region basis as
      follows: D = -(b(0)/b(1000))ln(S(b1000)/S(b0)), where S(b1000) is the signal
      intensity on DWI and S(b0) is the signal intensity on T2 with diffusion
      sensitivities of b(0) and b(1000), respectively. Computation of the T2R was made
      as follows: T2R = (TE(T2)--TE(PD))/(ln SI(PD)--ln SI(T2)), where TE is the echo
      time of the different pulse sequences, SI is signal intensity on the different
      echo sequences, and PD represents proton density sequence. RESULTS: Twenty-nine
      acute ischemia, 27 acute demyelination, 28 chronic ischemia, and 43 chronic
      demyelination image sets were analyzed. The differences between ADC(acute
      infarct) (0.760) versus ADC(acute plaque) (1.106) were significant (p < 0.02).
      The differences between T2R(acute infarct) (235.5) versus T2R(acute plaque)
      (170.5) were also significant (p < 0.02). CONCLUSIONS: ADC in combination with
      T2R is a useful tool to differentiate acute ischemic from acute demyelinating
      lesions. The use of these neuroimaging indices along with magnetic resonance
      spectroscopy metabolite ratios is then demonstrated in elucidating the
      pathophysiological mechanism for a case of delayed posttraumatic bilateral
      internuclear ophthalmoplegia.

PMID- 17531857
TI  - HLA-DRB1*1501, -DQB1*0301, -DQB1*0302, -DQB1*0602, and -DQB1*0603 alleles are
      associated with more severe disease outcome on MRI in patients with multiple
      sclerosis.
AB  - The most important confirmed genetic factor of susceptibility to multiple
      sclerosis (MS) has been identified in the HLA class II region. The hypothesis
      that several genes, including HLA class II, may influence the prognosis of
      patients with MS has been proposed. In a recent study, using low intermediate
      resolution typing, we found that some HLA alleles may predict disease severity as
      assessed by magnetic resonance imaging (MRI) measures. The aim of this study was
      to examine the relationship between high-resolution typing of HLA alleles and
      disease severity as measured by brain MRI quantitative markers of demyelinating
      and destructive pathology in patients with MS. In 41 MS patients (27 relapsing
      remitting, 7 secondary progressive, and 7 primary progressive), we performed high
      resolution typing of alleles HLA-DRB1*04, -DQB1*03, -DRB1*15, -DQB1*06, and of
      haplotypes -DRB1*04-DQB1*03 and -DRB1*15-DQB1*06. These alleles and haplotypes
      were associated with higher susceptibility to MS in a recently published case
      control study conducted in the Friuli-Venezia-Giulia region, Italy. Of 41
      included patients, 13 were men and 28 were women. Mean age was 43.3 (SD 11.4)
      years, mean disease duration 10.3 (SD 7.8) years, and mean EDSS 2.3. DNA
      extraction and genomic typing were obtained with the sequence-specific primers
      method using primer pairs that amplified the HLA alleles. All patients underwent
      a 1.5-T MRI examination of the brain. Disease severity was assessed by clinical
      measures [Expanded Disability Status Scale (EDSS)] and MRI measures. T2- and T1
      lesion volumes (LVs) and brain atrophy measures [fractions of brain parenchyma
      (BPF), gray matter (GMF), and white matter (WMF)] were calculated. We used
      general linear model analysis (GML), controlled for age, disease duration, and
      treatment status, to compare the MRI measures according to allele and haplotype
      status. The following significant results were found: HLA-DRB1*1501 positive
      patients had significantly lower GMF (0.493 vs 0.526, p < 0.001), lower BPF
      (0.784 vs 0.815, p = 0.018), and higher T1-LV (2.8 vs 0.7ml, p = 0.036); 
      DQB1*0301 positive patients had significantly higher T2-LV (34.1 vs 0.7 ml, p =
      0.041), and showed a trend for lower BPF (0.790 vs 0.846, p = 0.064); -DQB1*0302
      positive patients had significantly lower T1-LV (2.4 vs 0.9 ml, p = 0.016); and 
      DQB1*0602 positive patients had significantly lower GMF (0.492 vs 0.521, p =
      0.007) and lower BPF (0.781 vs 0.811, p = 0.023). No differences were found in
      the indices of MRI disease severity according to HLA haplotype associations. Both
      in correlation and in regression analyses, we observed significant associations
      between HLA-DRB1*1501 and lower GMF and BPF and higher T1-LV, between -DQB1*0301
      and higher T2-LV and disease duration, between -DQB1*0302 and lower GMF and
      higher T1- and T2-LV, between -DQB1*0602 and lower GMF and BPF, and between 
      DQB1*0603 and higher T1-LV and EDSS. High-resolution HLA genotyping analysis
      revealed a robust relationship between alleles HLA-DRB1*1501, -DQB1*0301, 
      DQB1*0302, -DQB1*0602, and -DQB1*0603, and more severe damage on inflammatory and
      neurodegenerative MRI measures.

PMID- 17531858
TI  - Glatiramer acetate: mechanisms of action in multiple sclerosis.
AB  - Glatiramer acetate (GA), formerly known as copolymer 1, is a mixture of synthetic
      polypeptides composed of four amino acids resembling the myelin basic protein
      (MSP). GA has been shown to be highly effective in preventing and suppressing
      experimental autoimmune encephalomyelitis (EAE), the animal model of multiple
      sclerosis (MS). Therefore, it was tested in several clinical studies and so
      approved for the immunomodulatory treatment of relapsing-type MS. In contrast to
      other immunomodulatory MS therapies, GA has a distinct mechanism of action: GA
      demonstrates an initial strong promiscuous binding to major histocompatibility
      complex molecules and consequent competition with various (myelin) antigens for
      their presentation to T cells. In addition, antigen-based therapy generating a GA
      specific immune response seems to be the prerequisite for GA therapy. GA
      treatment induces an in vivo change of the frequency, cytokine secretion pattern
      and the effector function of GA-specific CD4+ and CD8+ T cells, probably by
      affecting the properties of antigen-presenting cells such as monocytes and
      dendritic cells. As demonstrated extensively in animal experiments, GA-specific,
      mostly, T helper 2 cells migrate to the brain and lead to in situ bystander
      suppression of the inflammatory process in the brain. Furthermore, GA-specific
      cells in the brain express neurotrophic factors like the brain-derived
      neurotrophic factor (BDNF) in addition to anti-inflammatory T helper 2-like
      cytokines. This might help tip the balance in favor of more beneficial influences
      because there is a complex interplay between detrimental and beneficial factors
      and mediators in the inflammatory milieu of MS lesions.

PMID- 17531859
TI  - Evolving therapies for multiple sclerosis.
AB  - The introduction of immunomodulatory and immunosuppressive agents for treatment
      of multiple sclerosis (MS) has forever altered the natural course of this
      incurable and disabling neurodegenerative disorder. Despite early diagnosis of
      relapsing-remitting MS and early initiation of therapy, patients still experience
      breakthrough relapses and progression of their underlying MS pathology. The
      imperfect effectiveness, side effects, and toxicity of these agents, emphasize
      the necessity for development of more effective medications with less adverse
      events. This chapter presents readers with the most current information on the
      nature, mechanism(s) of action, and side effects of the most promising
      experimental agents currently under clinical trials. Some of the agents now at
      different stages of clinical trial have emerged as both safe and promising. The
      understanding of MS etiology will lead to the development of increasingly
      specific, safer, and effective treatments for MS by neuroscientists and
      neurologists.

PMID- 17531860
TI  - Remyelination in multiple sclerosis.
AB  - Remyelination is the phenomenon by which new myelin sheaths are generated around
      axons in the adult central nervous system (CNS). This follows the pathological
      loss of myelin in diseases like multiple sclerosis (MS). Remyelination can
      restore conduction properties to axons (thereby restoring neurological function)
      and is increasingly believed to exert a neuroprotective role on axons.
      Remyelination occurs in many MS lesions but becomes increasingly
      incomplete/inadequate and eventually fails in the majority of lesions and
      patients. Efforts to understand the causes for this failure of regeneration have
      fueled research into the biology of remyelination and the complex, interdependent
      cellular and molecular factors that regulate this process. Examination of the
      mechanisms of repair of experimental lesions has demonstrated that remyelination
      occurs in two major phases. The first consists of colonization of lesions by
      oligodendrocyte progenitor cells (OPCs), the second the differentiation of OPCs
      into myelinating oligodendrocytes that contact demyelinated axons to generate
      functional myelin sheaths. Several intracellular and extracellular molecules have
      been identified that mediate these two phases of repair. Theoretically, the
      repair of demyelinating lesions can be promoted by enhancing the intrinsic repair
      process (by providing one or more remyelination-enhancing factors or via
      immunoglobulin therapy). Alternatively, endogenous repair can be bypassed by
      introducing myelinogenic cells into demyelinated areas; several cellular
      candidates have been identified that can mediate repair of experimental
      demyelinating lesions. Future challenges confronting therapeutic strategies to
      enhance remyelination will involve the translation of findings from basic science
      to clinical demyelinating disease.

PMID- 17531861
TI  - Trigeminal neuralgia: a modern-day review.
AB  - OBJECTIVE: To review the disorder of trigeminal neuralgia (TN) in the context of
      previously known data and recent advancements. METHODS: A PubMed search (November
      25, 2006) was conducted, with review of existing literature related to this
      search. Review articles were accessed along with new advancements in diagnosis,
      pathophysiology, treatment, and prognosis. RESULTS: The diagnosis of TN is
      primarily based on clinical suspicion; ancillary tests can help rule out other
      associated pathology. Treatment includes medical and surgical treatment as
      previously described; recent radiosurgical treatment offers some success as well.
      Insights into pathophysiology have also been afforded by advances in imaging.
      CONCLUSIONS: TN is a complex but important disorder to diagnose; in the modern
      day context, appropriately diagnosed TN can be treated with a generally good
      prognosis.

PMID- 17531862
TI  - Optic neuritis and the neuro-ophthalmology of multiple sclerosis.
AB  - Multiple sclerosis (MS) is the most common cause of neurological disability in
      young adults. Since approximately 40% of the brain is devoted to vision,
      demyelination commonly affects visual function, resulting in a myriad of neuro
      ophthalmic symptoms. In this chapter, we examine the seminal afferent and
      efferent neuro-ophthalmological manifestations of MS, highlighting those history
      and examination findings critical for the diagnosis and treatment of various
      visual and ocular motor disorders. Among the topics, a special emphasis will be
      placed on optic neuritis, the most common clinically isolated demyelinating
      syndrome. This chapter focuses on the evaluation and treatment of visual sensory
      and oculomotor disorders in MS. The objective is to provide the reader with a
      working model for enhancing their care of patients with demyelinating disease.

PMID- 17531863
TI  - Neuromyelitis optica: new findings on pathogenesis.
AB  - Neuromyelitis optica (NMO) is an idiopathic CNS demyelinating disorder that
      preferentially involves the optic nerve and spinal cord. Diverse sources of
      evidence support the hypothesis that NMO is distinct from classical multiple
      sclerosis (MS) and that the pathogenesis of NMO is dominated by humoral
      mechanisms. Such evidence includes clinical observations that systemic autoimmune
      diseases often coexist with NMO and that therapeutic plasmapheresis may provide
      meaningful rescue therapy for severe clinical attacks, immunopathologic studies
      that demonstrate prominent complement activation and immunoglobulin deposition,
      and the discovery of the serum autoantibody NMO-IgG, a potential NMO biomarker
      that targets aquaporin-4 (AQP4). The NMO-IgG marker is present in a majority of
      patients with "NMO-spectrum disorders," including isolated or recurrent
      longitudinally extensive transverse myelitis, recurrent optic neuritis with
      negative brain imaging, and the Asian optic-spinal form of MS. Preliminary
      experiments demonstrate that NMO-IgG can modulate AQP4 function and fix
      complement, characteristics that suggest it has the potential to be pathogenic in
      NMO. Other immunologic differences among NMO, NMO-spectrum disorders, and
      classical MS are reviewed.

PMID- 17531864
TI  - International Health Regulations: the challenges ahead.

PMID- 17531865
TI  - Don't forget hypertension.

PMID- 17531866
TI  - A roadmap for new tuberculosis drugs.

PMID- 17531867
TI  - Fortification of processed cereals should be mandatory.

PMID- 17531868
TI  - The performance of the Global Fund.

PMID- 17531869
TI  - Personalised medicine: who is an Asian?

PMID- 17531870
TI  - A strategy for translation.

PMID- 17531871
TI  - The continuing battle over baby-milk formula.

PMID- 17531872
TI  - Clinical update: early surgery for acute cholecystitis.

PMID- 17531873
TI  - Simon Wessely.

PMID- 17531875
TI  - Risks associated with drug-eluting stents.

PMID- 17531876
TI  - Risks associated with drug-eluting stents.

PMID- 17531878
TI  - Small bowel leucocytoclastic vasculitis.

PMID- 17531880
TI  - Intensive statin regimens.

PMID- 17531881
TI  - ADHD: from childhood to adulthood.

PMID- 17531882
TI  - Adolescent health: an opportunity not to be missed.

PMID- 17531883
TI  - A code of ethics for scientists.

PMID- 17531884
TI  - Remember the links in the causal chain of fetal alcohol effects.

PMID- 17531885
TI  - Pelvic organ prolapse: don't forget developing countries.

PMID- 17531886
TI  - Direct-to-consumer drug advertisement in Europe.

PMID- 17531887
TI  - Efficacy of iron-fortified whole maize flour on iron status of schoolchildren in
      Kenya: a randomised controlled trial.
AB  - BACKGROUND: Sodium iron edetic acid (NaFeEDTA) might be a more bioavailable
      source of iron than electrolytic iron, when added to maize flour. We aimed to
      assess the effect, on children's iron status, of consumption of whole maize flour
      fortified with iron as NaFeEDTA or electrolytic iron. METHODS: 516 children, aged
      3-8 years, from four schools in Marafa, Kenya, were randomly assigned to four
      groups. All were given the same amount of porridge five times a week. The
      porridge for one group was made from unfortified whole maize flour; for the other
      three groups it was fortified with either high-dose NaFeEDTA (56 mg/kg), low-dose
      NaFeEDTA (28 mg/kg), or electrolytic iron (56 mg/kg). Concentrations of
      haemoglobin, plasma ferritin, and transferrin receptor were analysed in samples
      taken at baseline and at the end of the 5-month intervention. The primary outcome
      was iron-deficiency anaemia. We analysed data on an intention-to-treat basis.
      This trial is registered with ClinicalTrials.gov, number NCT00386074. FINDINGS:
      The prevalence of iron-deficiency anaemia in children given unfortified flour was
      10%. Compared with placebo, the prevalence of iron-deficiency anaemia in children
      given flour fortified with high-dose NaFeEDTA, low-dose NaFeEDTA, and
      electrolytic iron changed by -89% (95% CI -97% to -49%), -48% (-77% to 20%), and
      59% (-18% to 209%), respectively. Consumption of high-dose NaFeEDTA improved all
      measured iron-status indicators. Low-dose NaFeEDTA decreased the prevalence of
      iron deficiency but did not noticeably change the prevalence of anaemia.
      Electrolytic iron did not improve any of these iron-status indicators. Children
      who were iron-deficient at baseline benefited more from high-dose and low-dose
      NaFeEDTA than those with sufficient iron at baseline. INTERPRETATION: Consumption
      of whole maize flour fortified with NaFeEDTA caused modest, dose-dependent
      improvements in children's iron status. Fortification with electrolytic iron did
      not improve their iron status. Therefore, in high-phytate flours, NaFeEDTA is
      more suitable than electrolytic iron for supplementation of iron in the diet.

PMID- 17531888
TI  - Global Fund grant programmes: an analysis of evaluation scores.
AB  - BACKGROUND: The Global Fund to Fight AIDS, Tuberculosis and Malaria evaluates
      programme performance after 2 years to help decide whether to continue funding.
      We aimed to identify the correlation between programme evaluation scores and
      characteristics of the programme, the health sector, and the recipient country.
      METHODS: We obtained data on the first 140 Global Fund grants evaluated in 2006,
      and analysed 134 of these. We used an ordered probit multivariate analysis to
      link evaluation scores to different characteristics, allowing us to record the
      association between changes in those characteristics and the probability of a
      programme receiving a particular evaluation score. FINDINGS: Programmes that had
      government agencies as principal recipients, had a large amount of funding, were
      focused on malaria, had weak initial proposals, or were evaluated by the
      accounting firm KPMG, scored lowest. Countries with a high number of doctors per
      head, high measles immunisation rates, few health-sector donors, and high disease
      prevalence rates had higher evaluation scores. Poor countries, those with small
      government budget deficits, and those that have or have had socialist governments
      also received higher scores. INTERPRETATION: Our results show associations, not
      causality, and they focus on evaluation scores rather than actual performance of
      the programmes. Yet they provide some early indications of characteristics that
      can help the Global Fund identify and monitor programmes that might be at risk.
      The results should not be used to influence the distribution of funding, but
      rather to allocate resources for oversight and risk management.

PMID- 17531889
TI  - 9 years of recurrent dysphagia.

PMID- 17531890
TI  - Repetitive strain injury.
AB  - Repetitive strain injury remains a controversial topic. The term repetitive
      strain injury includes specific disorders such as carpal tunnel syndrome, cubital
      tunnel syndrome, Guyon canal syndrome, lateral epicondylitis, and tendonitis of
      the wrist or hand. The diagnosis is usually made on the basis of history and
      clinical examination. Large high-quality studies using newer imaging techniques,
      such as MRI and ultrasonography are few. Consequently, the role of such imaging
      in diagnosis of upper limb disorders remains unclear. In many cases, no specific
      diagnosis can be established and complaints are labelled as non-specific. Little
      is known about the effectiveness of treatment options for upper limb disorders.
      Strong evidence for any intervention is scarce and the effect, if any, is mainly
      short-term pain relief. Exercise is beneficial for non-specific upper limb
      disorders. Immobilising hand braces and open carpal tunnel surgery release are
      beneficial for carpal tunnel syndrome, and topical and oral non-steroidal anti
      inflammatory drugs, and corticosteroid injections are helpful for lateral
      epicondylitis. Exercise is probably beneficial for neck pain, as are
      corticosteroid injections and exercise for shoulder pain. Although upper limb
      disorders occur frequently in the working population, most trials have not
      exclusively included a working population or assessed effects on work-related
      outcomes. Further high-quality trials should aim to include sufficient sample
      sizes, working populations, and work-related outcomes.

PMID- 17531891
TI  - Acute and chronic complications of type 2 diabetes mellitus in children and
      adolescents.
AB  - With the increase in prevalence of type 2 diabetes mellitus in adolescents, a
      rise in incidence of secondary comorbidities--including hypertension,
      hyperlipidaemia, nephropathy, and retinopathy--is anticipated. Furthermore,
      findings of studies in young adults have suggested that the development and
      progression of clinical complications might be especially rapid when the onset of
      type 2 diabetes is early, raising the possibility of a serious public-health
      challenge in the next few decades. To date, reports of the epidemiology and
      natural history of secondary complications specifically in adolescents with type
      2 diabetes have been scarce. Yet, we must begin to understand the extent of the
      coming challenge. To this end, we have reviewed reports on acute and long-term
      comorbidities associated with type 2 diabetes in young people and have looked at
      mounting evidence that this group could be at increased risk for development of
      early complications.

PMID- 17531892
TI  - A mimic of sarcoidosis.

PMID- 17531894
TI  - Fetal growth restriction and subsequent pregnancy risks.
AB  - Fetal growth restriction can result from a variety of intrinsic or extrinsic
      insults, resulting from maternal, fetal, and placental factors. Determining the
      underlying cause of poor fetal growth can be difficult but is essential for
      assessing potential risks for future pregnancies. Importantly, recurrence risks
      greatly depend on these underlying conditions. Understanding these risks can
      allow more appropriate patient counseling and may influence management strategies
      to optimize future pregnancies.

PMID- 17531895
TI  - Preeclampsia recurrence and prevention.
AB  - Women with a previous pregnancy complicated by preeclampsia have an increased
      risk for recurrence in subsequent pregnancies. For severe preeclamptic women in
      an initial pregnancy, recurrence rates for any type of preeclampsia are very
      high, approaching 50% in some studies. Significant maternal and fetal
      complications are more common in recurrent preeclampsia compared with an initial
      episode. For women who have experienced a pregnancy complicated by preeclampsia,
      a systematic evaluation for underlying risk factors may identify a specific
      pathway suitable for a specific intervention. Although some progress has been
      made in developing potential therapeutic options to prevent preeclampsia
      recurrence, there is a great need for better data to determine who will benefit
      most from any specific therapy.

PMID- 17531897
TI  - Postpartum hemorrhage: a recurring pregnancy complication.
AB  - Postpartum hemorrhage (PPH) is a potentially life-threatening complication of
      both vaginal and cesarean deliveries. Although many variables increase the chance
      for bleeding, a PPH in a previous pregnancy is one of the greatest risk factors
      for recurrent PPH. A physiologic explanation for this association is not known,
      but recurrent risk factors such as a retained placenta or underlying medical
      disorders may account for the majority of recurrent PPH cases. To reduce maternal
      morbidity and mortality, prevention of PPH in these patients is critical. Steps
      to minimize hemorrhagic complications include the identification of high-risk
      patients through a complete history, vigilant management of the third stage of
      labor, and having uterotonic medications readily available in the delivery room.
      Patients with inherited coagulopathies require individualized treatment, and
      their risks for bleeding extend beyond the first 24 hours after delivery. Further
      studies are needed to determine whether the administration of prophylactic
      measures such as prostaglandins decrease the PPH occurrence in high-risk
      patients.

PMID- 17531898
TI  - Thromboembolism in pregnancy: recurrence and its prevention.
AB  - Fifteen to 25% of thromboembolic events in pregnancy are recurrent events. Women
      with a history of thrombosis have a three- to fourfold increased risk of
      recurrence when they are pregnant compared with when they are not. The risks are
      even higher postpartum. The rate of recurrent venous thromboembolic events
      without anticoagulation is 2.4% to 12.2%, whereas the rate with anticoagulation
      is 0% to 2.4%. Because the rates of recurrent thromboembolism can be reduced with
      anticoagulation, women with a history of thrombosis who are not on lifelong
      anticoagulation will likely require anticoagulation during pregnancy, or at least
      during the postpartum period. Women who are already on lifelong warfarin for the
      prevention of recurrent venous thromboembolism should be counseled about the
      teratogenic effects of warfarin and offered the opportunity to be converted to
      heparin before conception. During pregnancy, low-molecular-weight heparin, with
      fewer side effects and a longer half-life, is generally preferred over
      unfractionated heparin. Unfractionated heparin with its shorter half-life is
      generally preferred around the time of delivery. Women on antiplatelet medication
      for prevention of arterial thromboembolism may be converted to low-dose aspirin
      after conception and supplemented with low-dose heparin or low-molecular-weight
      heparin during pregnancy. Because current recommendations rely on case series and
      expert opinion, additional studies including randomized trials might enhance our
      ability to prevent recurrent thromboembolism in pregnancy.

PMID- 17531899
TI  - Recurrent gestational diabetes: risk factors, diagnosis, management, and
      implications.
AB  - Gestational diabetes mellitus (GDM) should be regarded as a sentinel event in a
      woman's life that presents challenges and disease prevention opportunities to all
      providers of health care for women of reproductive age. Prediabetic risk factors
      are rising in prevalence and include dietary and lifestyle habits, which when
      superimposed on genetic predisposition contribute to the rising prevalence of
      type 2 diabetes and GDM. There is growing evidence that treatment of GDM matters,
      with a continuum of adverse pregnancy outcome risks proportional to degrees of
      maternal glucose intolerance. GDM in an index pregnancy increases the risk of
      recurrent GDM in subsequent pregnancies, and recurrence rates of up to 70% have
      been reported. GDM recurrence rates are influenced by maternal health
      characteristics and past pregnancy history. The risk of later metabolic syndrome
      and type 2 diabetes is increased in women with a history of GDM and women should
      be screened for postpartum glucose intolerance. Opportunities to prevent
      recurrent GDM and later type 2 diabetes require attention to risk factors and
      plasma glucose status with identification of impaired fasting glucose or impaired
      glucose tolerance.

PMID- 17531896
TI  - Recurrent preterm birth.
AB  - Recurrent preterm birth is frequently defined as two or more deliveries before 37
      completed weeks of gestation. The recurrence rate varies as a function of the
      antecedent for preterm birth: spontaneous versus indicated. Spontaneous preterm
      birth is the result of either preterm labor with intact membranes or preterm
      prelabor rupture of the membranes. This article reviews the body of literature
      describing the risk of recurrence of spontaneous and indicated preterm birth.
      Also discussed are the factors which modify the risk for recurrent spontaneous
      preterm birth (a short sonographic cervical length and a positive cervicovaginal
      fetal fibronectin test). Patients with a history of an indicated preterm birth
      are at risk not only for recurrence of this subtype, but also for spontaneous
      preterm birth. Individuals of black origin have a higher rate of recurrent
      preterm birth.

PMID- 17531900
TI  - After shoulder dystocia: managing the subsequent pregnancy and delivery.
AB  - Among risk factors for shoulder dystocia, a prior history of delivery complicated
      by shoulder dystocia is the single greatest risk factor for shoulder dystocia
      occurrence, with odds ratios 7 to 10 times that of the general population.
      Recurrence rates have been reported to be as high as 16%. Whereas prevention of
      shoulder dystocia in the general population is neither feasible nor cost
      effective, intervention efforts directed at the particular subgroup of women with
      a prior history of shoulder dystocia can concentrate on potentially modifiable
      risk factors and individualized management strategies that can minimize
      recurrence and the associated significant morbidities and mortality.

PMID- 17531901
TI  - Epidemiologic approaches for studying recurrent pregnancy outcomes: challenges
      and implications for research.
AB  - The study of recurrence of pregnancy-related complications and outcomes can offer
      powerful insights to understanding patient-related risks for subsequent
      pregnancies. Such studies, when designed, analyzed, and interpreted correctly,
      can help distinguish genetic from environmental causes that portend increased
      recurrence of a particular pregnancy complication (eg, recurrence of gestational
      diabetes) or a perinatal outcome (eg, recurrence of preterm birth or
      preeclampsia). Recurrence risk studies can be challenging in other dimensions,
      including inherent biases, generalizability of findings, inadequate study size,
      and inappropriate use of analytic models to study recurrence. Other common
      misperceptions in studies of recurrence risk are highlighted, including issues
      with terminology and interpretation of recurrence risks. A review of available
      epidemiologic study designs is presented and the usefulness and applicability of
      each design for addressing specific etiologic questions as they relate to
      recurrence risks are contrasted.

PMID- 17531903
TI  - Management of acute decompensated heart failure.
AB  - Acute decompensated heart failure is the most common cause for hospitalization
      among patients over 65 years of age. It may result from new onset of ventricular
      dysfunction or, more typically, exacerbation of chronic heart failure symptoms.
      In-hospital mortality remains high for both systolic and diastolic forms of the
      disease. Therapy is largely empirical as few randomized, controlled trials have
      focused on this population and consensus practice guidelines are just beginning
      to be formulated. Treatment should be focused upon correction of volume overload,
      identifying potential precipitating causes, and optimizing vasodilator and beta
      adrenergic blocker therapy. The majority of patients (>90%) will improve without
      the use of positive inotropic agents, which should be reserved for patients with
      refractory hypotension, cardiogenic shock, end-organ dysfunction, or failure to
      respond to conventional oral and/or intravenous diuretics and vasodilators. The
      role of aldosterone antagonists, biventricular pacing, and novel pharmacological
      agents including vasopressin antagonists, endothelin blockers, and calcium
      sensitizing agents is also reviewed.

PMID- 17531904
TI  - Clinical impact of MRI assisted dose volume adaptation and dose escalation in
      brachytherapy of locally advanced cervix cancer.
AB  - BACKGROUND: To investigate the clinical impact of MRI based cervix cancer
      brachytherapy combined with external beam radiochemotherapy applying dose volume
      adaptation and dose escalation in a consecutive group of patients with locally
      advanced cervix cancer. METHODS: In the period 1998-2003, 145 patients with
      cervix cancer stages IB-IVA were treated with definitive radiotherapy +/-
      cisplatin chemotherapy. Median age was 60 years. In 67 patients, the tumour size
      was 2-5 cm, in 78 patients it was >5 cm. In 29 cases the standard intracavitary
      technique was combined with interstitial brachytherapy. Total prescribed dose was
      80-85 Gy (total biologically equivalent dose in 2 Gy fractions). Since 2001, MRI
      based treatment planning integrated systematic concepts for High Risk Clinical
      Target Volume (HR CTV) and organs at risk (OAR), biological modelling, Dose
      Volume-Histogram analysis, dose-volume-adaptation (D90, D 2 cm(3)), and dose
      escalation, if appropriate and feasible. FINDINGS: Dose volume adaptation was
      performed in 130/145 patients. The mean D90 during the whole period was 86 Gy,
      with a mean D90 of 81 Gy and 90 Gy during the first and second period,
      respectively (p<<0.01). Median follow-up was 51 months. Complete remission at 3
      months was achieved in 138/145 patients (95%). Actuarial continuous complete
      remission for true pelvis (CCRtp) was 88% at 3 years. For tumours 2-5 cm, CCRtp
      was 96% both in 1998-2000 and 2001-2003. For tumours >5 cm it was 71% in 1998
      2000 and 90% in 2001-2003 (p=0.05). Progression free survival (PFS) for true
      pelvis (local control) was 85%, PFS for distant metastases was 80%, both at 3
      years. Local control for tumours >5 cm was 64% in 1998-2000 and 82% in 2001-2003
      (p=0.09) and 100% and 96%, respectively, for tumours 2-5 cm. PFS for distant
      metastases remained the same during the two treatment periods with 79% and 80%.
      Overall survival (OS) was 58%, and cancer-specific survival (CSS) was 68% at 3
      years. In the two different periods improvement in OS was from 53% to 64%
      (p=0.03) and in CSS from 62% to 74% (p=0.13). Improvement occurred only in
      tumours >5 cm: OS 28% versus 58% (p=0.003); CSS 40% versus 62% (p=0.07).
      Actuarial late morbidity rate (LENT SOMA, grades 3 and 4) at 3 years was
      gastrointestinal 4%, urinary 4% and vaginal 5% (stage IIA/IIIA). Gastrointestinal
      and urinary late morbidity (G3,G4) was 10% in 1998-2000 and 2% in 2001-2003.
      INTERPRETATION: In locally advanced extensive cervix cancer, local control of >
      or = 85% can be achieved with low treatment related morbidity (G3/G4), when
      exploiting the potential of MRI based 3D treatment planning including dose volume
      adaptation and dose escalation and a combined intracavitary/interstitial
      brachytherapy, if appropriate. A significant impact of this improvement of local
      control on survival is to be expected. For locally advanced limited disease the
      MRI based approach will likely result in assuring excellent local control (> or =
      95%) and in minimizing treatment related morbidity.

PMID- 17531905
TI  - Physician-reported practice of the use of methylphenidate in Japanese palliative
      care units.

PMID- 17531906
TI  - An unusual cause of movement disorder in a young man with penile carcinoma.

PMID- 17531907
TI  - Hidden pain or hidden evidence?

PMID- 17531909
TI  - The desire for hastened death in patients with metastatic cancer.
AB  - A substantial minority of patients in palliative care settings report a high
      desire for hastened death (DHD), in association with physical and emotional
      distress, low social support, and impaired spiritual well being. To clarify to
      what extent DHD emerges in association with suffering prior to the end of life,
      we determined its prevalence and correlates in ambulatory patients with
      metastatic cancer, the majority of whom had an expected survival of >6 months. We
      hypothesized that DHD in this sample would be directly linked to physical and
      psychological distress, and inversely related to perceived social support, self
      esteem, and spiritual well being. Three hundred twenty-six outpatients completed
      the Schedule of Attitudes Toward Hastened Death (SAHD), Brief Pain Inventory,
      Memorial Symptom Assessment Scale, Beck Depression Inventory-II (BDI-II), Beck
      Hopelessness Scale (BHS), Medical Outcomes Study Social Support Survey, FACIT
      Spiritual Well-Being Scale, Rosenberg Self-Esteem Scale, and Karnofsky
      Performance Status. Over 50% of participants reported pain, >20% reported
      elevated levels of depression (BDI-II> or =15) and hopelessness (BHS> or =8), but
      <2% had a high DHD (SAHD> or =10). DHD was correlated positively with
      hopelessness, depression, and physical distress, and negatively with physical
      functioning, spiritual well being, social support, and self-esteem; it was not
      associated with treatment status or proximity to death. Over 34% of the variance
      in predicting SAHD scores was accounted for by hopelessness, depression, and
      functional status. The relative absence of a strong DHD in this sample suggests
      that the will to live tends to be preserved in cancer patients prior to the end
      of life, in spite of significant emotional and physical suffering.

PMID- 17531910
TI  - Hospice and palliative care development in Africa: a multi-method review of
      services and experiences.
AB  - There is a paucity of information on hospice and palliative care provision in
      Africa and only a weak evidence base upon which to build policy and practice
      development. We set out to assess the current state of provision across the
      continent, mapping the existence of services country by country and exploring the
      perspectives and experiences of those involved. A multi-method review was
      conducted involving a synthesis of evidence from published and gray literature,
      ethnographic field visits to seven countries, qualitative interviews with 94
      individuals from 14 countries, and the collation of existing public health data.
      Forty-seven African countries were reviewed, involving the assistance of numerous
      hospice and palliative care activists, including clinicians, managers,
      volunteers, policy makers, and staff of donor organizations. The 47 countries of
      Africa could be grouped into four categories: no identified hospice or palliative
      care activity (21 countries); capacity building activity is underway to promote
      hospice and palliative care delivery (11 countries); localized provision of
      hospice and palliative care is in place, often heavily supported by external
      donors (11 countries); and hospice and palliative care services are approaching
      some measure of integration with mainstream service providers and gaining wider
      policy recognition (four countries). Overall, services remain scattered and
      piecemeal in most African countries, and coverage is poor. Nongovernmental
      organizations are the predominant source of provision. Major difficulties relate
      to opioid availability, workforce development, and achieving sustainable critical
      mass. Models exist in Uganda, Kenya, South Africa, and Zimbabwe for the
      development of affordable, sustainable community-based hospice and palliative
      care services, but sensitivity is required in adopting Western models of hospice
      and palliative care for implementation in the African cultural context. Overall,
      interest in the development of hospice and palliative care in Africa has never
      been greater.

PMID- 17531911
TI  - End-of-life care in hospital: current practice and potentials for improvement.
AB  - From July until September 2004, all deaths were registered prospectively in all
      departments of Freiburg University Hospital, Germany, a large teaching hospital
      with approximately 55,000 inpatient admissions per year. A retrospective chart
      review was done for all patients who died during this time period using a tool
      validated in two American and Australian projects. Main outcome measures were
      patients' identification as dying by medical staff, Do-Not-Resuscitate (DNR)
      orders, and the presence of comfort care plans. The cohort comprised 226
      consecutive death events. Seven percent of patients had a written advance
      directive. DNR orders were available for 65% of patients and were entered into
      the charts on average 5.9 days prior to death. Thirty-eight percent of charts had
      evidence that staff recognized that the patients were dying. This prognosis was
      noted on average 3.8 days prior to death. According to chart notes, clinicians
      documented cancer patients as dying more frequently than patients with
      cardiovascular disease (P=0.029). In the chart entries, comfort care plans were
      completed fully for 14% and partially for 27% of patients. On average, comfort
      care plans were put in place nine days prior to death. Cancer patients had
      significantly more frequent comfort care plans than patients with cardiovascular
      diseases (P<0.001). In 59% of medical charts, there was no evidence of a comfort
      plan. Approximately one-third of dying patients received active life-sustaining
      treatment at time of death. These data highlight the need for systematic
      strategies to monitor patients' needs and to improve quality of care, especially
      during the last four days before death.

PMID- 17531912
TI  - Validation of the French version of the brief pain inventory in Canadian veterans
      suffering from traumatic stress.
AB  - Although pain is a significant clinical problem in individuals suffering from
      post-traumatic stress disorder (PTSD), reliable and valid measures of pain for
      this population are lacking. The goal of this study was to validate the Brief
      Pain Inventory (BPI) in French-speaking veterans suffering from PTSD (n=130). We
      administered the BPI, as well as measures of PTSD, health status, quality of
      life, and social desirability, to veterans being assessed or treated for PTSD at
      a Veterans Affairs Canada clinic. The BPI showed strong internal consistency, as
      evidenced by Cronbach's alphas of 0.90 and 0.92 for the severity and interference
      subscales, respectively. Similar to previous findings, a two-factor structure
      (pain severity and pain interference) was found using an exploratory factor
      analysis. The two factors explained nearly 73% of the variance of the instrument.
      The BPI was also strongly correlated with health status and quality of life in
      the physical domain. In this veteran sample, nearly 87% of the veterans suffered
      from significant current pain. Veterans in our sample reported rates of pain
      severity that were similar to or higher than most of those reported by cancer
      patients and others with significant physical disability/illness. Overall, the
      French version of the BPI is a reliable, valid measure of pain in PTSD-suffering
      populations. Pain is a major issue in veterans with PTSD, and should be screened
      for with instruments such as the BPI.

PMID- 17531913
TI  - A questionnaire to evaluate the knowledge and attitudes of health care providers
      on pain.
AB  - The aims of this study were to survey the knowledge and attitudes of Italian
      health care professionals toward pain and develop a valid instrument to assess
      pain knowledge of physicians and nurses. A 21-item questionnaire on a Likert
      scale was given to 4,961 health professionals in 20 hospitals in Italy who
      volunteered to participate in the study. The results were analyzed
      psychometrically in three phases: the Principal Component Analysis phase
      identified two components, of which only the one that had 10 items about pain
      knowledge and attitudes (PAK) was studied; the Homogeneity Analysis revealed its
      acceptable internal reliability (Cronbach's alpha=0.72) and confirmed the Likert
      equidistance of the item options response; and the Confirmatory Factor Analysis
      proved that it had a very good construct validity. A standardized score was
      calculated on the PAK questionnaire using the final 10 selected items,
      considering 100% as the best level of knowledge of pain management and 0% as the
      worst. The standardized mean score on the whole sample was equal to 52.6% (95%
      Confidence Interval: 52.3%-53.0%). There was a statistically significant
      difference (P<0.001) in percentage score between physicians (56.5%) and nurses
      (51.3%). Knowledge was best among physicians in Anesthesiology and Emergency;
      this was followed by doctors in Medicine and then surgeons. The knowledge of
      nurses was almost constant. This scale fills a void by providing a validated
      instrument for testing the general knowledge about pain treatment of hospital
      staff. It is brief and can easily be administered to a considerable number of
      people.

PMID- 17531914
TI  - The national agenda for quality palliative care: the National Consensus Project
      and the National Quality Forum.
AB  - The release in 2007 of the National Quality Forum (NQF) preferred practices is a
      significant advance in the field of palliative care. These NQF preferred
      practices build on the clinical practice guidelines for palliative care developed
      by the National Consensus Project (NCP). The NQF is dedicated to improving the
      quality of American health care, and their focus on palliative care recognizes
      its growing place within the broader scope of health care. This article reviews
      the work of both the NCP and NQF and presents the domains and preferred practices
      that should guide quality improvement efforts in hospice and palliative care.

PMID- 17531915
TI  - Risk-factor clustering and cardiovascular disease risk in hypertensive patients.
AB  - BACKGROUND: Patients with hypertension often have other major risk factors for
      cardiovascular disease (CVD). Little is known, however, about the extent of risk
      factor clustering in these patients and its importance in CVD risk and medical
      care costs. METHODS: Study subjects were selected from the electronic medical
      records system of Kaiser Permanente Northwest, a large health maintenance
      organization, and included all patients aged > or =35 years with hypertension who
      were free of CVD in 1998. Subjects were stratified into eight risk-factor
      clusters based on whether or not they also had diabetes, hyperlipidemia, or a
      high body mass index (BMI). The risk of cardiovascular events was examined in
      each cluster over 6 years beginning January 1, 1999, using Kaplan-Meier methods
      and Cox proportional hazards models. Cumulative total medical-care costs (per
      patient) over 6 years also were examined. RESULTS: A total of 57,573 patients
      with hypertension who were free of CVD in 1998 were identified; 56% of subjects
      also had diabetes, hyperlipidemia, or high BMI. In analyses controlling for age,
      sex, and smoking status, the relative risk of cardiovascular events over 6 years
      was highest for patients with comorbid diabetes, ranging from 2.07 (95%
      confidence interval, 1.86-2.30) for those with diabetes only to 2.80 (95%
      confidence interval, 2.48-3.17) for those with diabetes, hyperlipidemia, and high
      BMI. Cumulative medical-care costs generally increased with additional risk
      factors. Comorbid diabetes had the greatest impact on costs over 6 years.
      CONCLUSIONS: More than 50% of patients with hypertension also had diabetes,
      hyperlipidemia, or high BMI. Patients with these additional risk factors
      (especially diabetes) had a substantially higher CVD risk and medical-care costs.

PMID- 17531916
TI  - Cardiorespiratory fitness and risk of nonfatal cardiovascular disease in women
      and men with hypertension.
AB  - BACKGROUND: Whether the cardioprotective characteristic of higher
      cardiorespiratory fitness (CRF) extends to adults with manifest hypertension
      (HTN) is poorly understood. METHODS: We examined the association between CRF and
      nonfatal cardiovascular disease (CVD) events in 8147 men and 1268 women, who, at
      baseline, were free of known CVD and had HTN based on a history of physician
      diagnosis or a measured resting blood pressure (BP) > or =140/90 mm Hg. The CVD
      events (myocardial infarction, stroke, coronary revascularization) were
      ascertained from mail-back surveys. The CRF was quantified as maximal treadmill
      exercise test duration and was grouped for analysis as low (lowest 20% of
      exercise duration), moderate (middle 40%), and high (upper 40%). RESULTS: A total
      of 71 CVD events occurred during 12,224 woman-years, and 837 CVD events occurred
      during 82,366 man-years of follow-up. Age and examination year adjusted CVD rates
      per 1000 person-years according to low, moderate, and high CRF groups were 10.8,
      8.4, and 3.8 (trend P = .001) in women, and were 15.3, 10.9, and 7.2 (trend P <
      .001) in men. After further controlling for CVD risk factors, abnormal exercise
      electrocardiogram (ECG) responses, and family history of CVD, hazards ratios (95%
      CI) for CVD events across incremental CRF categories were 1.00 (referent), 0.88
      (0.74 to 1.06), 0.70 (0.57 to 0.86), trend P < .001, in men, and were 1.00
      (referent), 0.87 (0.48 to 1.58), 0.41 (0.20 to 0.84), trend P = .01, in women.
      CONCLUSIONS: In adults with HTN, higher CRF is associated with lower risk of
      nonfatal CVD events, independent of other clinical risk predictors.

PMID- 17531917
TI  - Home blood pressure is as reliable as ambulatory blood pressure in predicting
      target-organ damage in hypertension.
AB  - BACKGROUND: Our objective was to assess the value of home blood pressure (BP)
      monitoring in comparison to office BP measurements and ambulatory monitoring in
      predicting hypertension-induced target-organ damage. METHODS: Sixty-eight
      untreated patients with hypertension with at least two routine prestudy office
      visits were included (mean age, 48.6 +/- 9.1 [SD] years; 50 men). Office BP was
      measured in two study visits, home BP was measured for 6 workdays, and ambulatory
      BP was monitored for 24 h. All BP measurements were obtained using validated
      electronic devices. Target-organ damage was assessed by measuring the
      echocardiographic left-ventricular mass index (LVMI), urinary albumin excretion
      rate (AER) in two overnight urine collections, and carotid-femoral pulse-wave
      velocity (PWV) (Complior device; Colson, Garges-les-Gonesse, Paris, France).
      RESULTS: The correlation coefficients of LVMI with office BP were 0.24/0.15
      (systolic/diastolic), with home BP 0.35/0.21 (systolic, P < .01), and with 24-h
      ambulatory BP 0.23/0.19, awake 0.21/0.16, and asleep 0.28/0.26 (asleep, both P <
      .05). The correlation coefficients of AER with office BP were 0.24/0.31
      (diastolic, P < .05), with home BP 0.28/0.26 (both P < .05), and with 24-h
      ambulatory BP 0.25/0.24, awake 0.24/0.25 (diastolic, P < .05), and asleep
      0.26/0.18 (systolic, P < .05). There was a trend for negative correlations
      between PWV and diastolic BP measurements (not significant). In multiple
      regression models assessing independent predictors of each of the three indices
      of target-organ damage, systolic home BP and age were the only independent
      predictors of increased LVMI that reached borderline statistical significance.
      CONCLUSIONS: These data suggest that home BP is as reliable as ambulatory
      monitoring in predicting hypertension-induced target-organ damage, and is
      superior to carefully taken office measurements.

PMID- 17531918
TI  - Arterial-wave reflections are increased in heart failure patients with a left
      ventricular assist device.
AB  - BACKGROUND: Chronic heart failure (HF) is associated with increased central
      arterial pulse-wave reflections, which may contribute to increased myocardial
      oxygen demand. Although the treatment of HF via left-ventricular assist device
      (LVAD) placement has recently become widespread, the effects of LVAD therapy on
      central arterial pulse-wave reflections are unknown. METHODS: Central aortic
      pulse-wave analysis was performed on patients with end-stage HF awaiting cardiac
      transplantation and on healthy age-matched controls using the SphygmoCor (Akor
      Medical, Sydney, Australia) system. Arterial pulse-wave data were compared
      between patients receiving LVAD support versus those receiving intravenous
      inotropic drugs and healthy control patients. RESULTS: Five patients on LVAD
      support were compared with 10 patients on inotropic drugs and 10 healthy control
      patients. Aortic augmented pressure and the aortic augmentation index (AI(a))
      were higher in LVAD patients compared with inotrope and control patients, despite
      similar brachial and aortic blood pressures between groups. The AI(a) was
      significantly higher in LVAD patients than in patients on inotropic drugs (28.2%
      +/- 10% v 7.9% +/- 9%, P < or = .01). Additionally, there was a significantly
      higher aortic systolic tension time index, an index of left-ventricular
      myocardial oxygen demand, in the LVAD group compared with the inotrope group
      (2655 +/- 298 mm Hg/sec/min v 1748 +/- 303 mm Hg/sec/min, P < .01). CONCLUSIONS:
      Central arterial pressure-wave reflection is increased in end-stage HF patients
      on LVAD support compared with those on inotropic drugs, leading to an increase in
      aortic augmented pressure, AI(a), and systolic tension time index. The AI(a) is
      also higher in LVAD patients than in healthy controls. This increased central
      arterial-wave reflection places an additional hemodynamic load on the LVAD device
      and may have relevance to the medical management of patients after LVAD placement
      and to the longevity of the LVAD device itself.

PMID- 17531919
TI  - Attenuation of hypertension development by aminoguanidine in spontaneously
      hypertensive rats: role of methylglyoxal.
AB  - BACKGROUND: Methylglyoxal (MG), a metabolite of glucose, and MG-induced advanced
      glycation endproducts (AGEs) are causatively associated with vascular
      complications of diabetes mellitus. We have previously reported elevated levels
      of MG and MG-induced AGEs in spontaneously hypertensive rats (SHR). The purpose
      of this study was to investigate the causative role of MG and MG-induced AGEs in
      the pathogenesis of hypertension in SHR. METHODS: Young SHR were treated with an
      AGE inhibitor, aminoguanidine, for 9 weeks. HPLC was used to determine plasma and
      aortic MG and reduced glutathione levels. The MG-induced AGEs, N epsilon
      carboxyethyl-lysine (CEL) and argpyramidine, in the aorta were determined by
      immunohistochemistry. Vascular relaxation of small mesenteric arteries was
      measured using myograph. RESULTS: Chronic treatment with aminoguanidine
      attenuated age-dependent blood pressure (BP) increase in SHR. Plasma and aortic
      MG levels, and aortic levels of MG-induced AGEs, were significantly reduced after
      aminoguanidine treatment, which were comparable to those from age-matched Wistar
      Kyoto rats. Free radical level was significantly lowered, whereas reduced
      glutathione level was significantly increased by aminoguanidine treatment in the
      aortic tissues from SHR. Moreover, aminoguanidine therapy prevented the
      morphologic damage of vascular tissues in SHR and restored the endothelium
      dependent relaxation to acetylcholine. Chronic aminoguanidine treatment also
      increased aortic endothelial nitric oxide synthase expression and reduced
      inducible nitric oxide synthase expression. CONCLUSIONS: The MG and MG-induced
      AGEs contribute to the pathogenesis of hypertension by altering the redox
      balance, causing vascular eutrophic inward remodeling, and inducing endothelial
      dysfunction in SHR.

PMID- 17531920
TI  - Acute effects of cigarette smoking on arterial stiffness and blood pressure in
      male smokers with hypertension.
AB  - BACKGROUND: Although the acute increase of arterial stiffness and blood pressure
      (BP) after cigarette smoking in healthy smokers is considered a possible
      mechanism of increased cardiovascular risk, the acute effect of smoking on
      arterial stiffness in hypertensive smokers is unknown. We investigated the acute
      effects of cigarette smoking on arterial stiffness and BP in hypertensive male
      smokers. METHODS: Heart rate (HR), brachial and ankle BP, and pulse-wave velocity
      (PWV) were measured in 22 hypertensive male smokers (HTs) and in 30 normotensive
      male smokers (NTs) before and 5, 10, and 15 min after smoking one cigarette
      (nicotine content, 0.9 mg). RESULTS: Smoking induced acute increases of HR,
      brachial BP, and heart-femoral PWV (hfPWV) in NTs and HTs (P < .05). Ankle
      systolic BP and femoral-ankle PWV were acutely increased in HTs (P < .05), but
      not in NTs. In HTs, brachial systolic BP and hfPWV at 15 min were higher than at
      baseline (P < .05). An acute increase of hfPWV in the HTs was significant (P =
      .025) after adjustment for total cholesterol, time-dependent HR, and brachial
      mean arterial pressure, but acute changes of other PWVs lost statistical
      significance. CONCLUSIONS: Cigarette smoking acutely increases aortic stiffness
      and BP in male smokers with hypertension, and the effects persist longer than in
      male smokers without hypertension.

PMID- 17531921
TI  - Augmentation index and central aortic stiffness in middle-aged to elderly
      individuals.
AB  - BACKGROUND: Increased aortic stiffness contributes to systolic hypertension and
      increased cardiovascular risk. The augmentation index (AI), ie, the percentage of
      central pulse pressure attributed to reflected wave overlap in systole, was
      proposed as a noninvasive indicator of increased arterial stiffness. We evaluated
      this hypothesis by investigating relations between AI and other direct measures
      of aortic stiffness. METHODS: Tonometric carotid- and femoral-pressure waveforms,
      Doppler aortic flow, and aortic-root diameter were assessed in 123 individuals
      with uncomplicated systolic hypertension and 29 controls of comparable age and
      sex. Carotid-femoral pulse-wave velocity (PWV) was assessed from the carotid
      femoral time delay and body-surface measurements. Aortic PWV was assessed from
      the ratio of the upstroke of carotid pressure and aortic flow velocity and was
      used to calculate proximal aortic compliance as [aortic area]/[1.06 x (aortic
      PWV)(2)]. RESULTS: Partial correlations (adjusted for age, sex, presence of
      hypertension, height, weight, and systolic ejection period) showed no association
      between AI and carotid-femoral PWV (R = -0.05, P = .54). The AI was significantly
      though weakly related directly with aortic compliance (R = 0.21, P = .012) and
      inversely with aortic PWV (R = -0.198, P = .017). However, higher stiffness
      (lower compliance and higher PWV) was associated with lower AI. CONCLUSIONS:
      Increased AI is not a reliable surrogate for increased aortic stiffness.
      Decreasing AI with decreasing compliance (increasing aortic stiffness) may be
      attributable to impedance matching and reduced wave reflection at the interface
      between the aorta and the muscular arteries.

PMID- 17531922
TI  - Dissociation between central augmentation index and carotid-femoral pulse-wave
      velocity: when and why?

PMID- 17531923
TI  - Sex differences in the relationship between estrogen receptor alpha gene
      polymorphisms and arterial stiffness in older humans.
AB  - BACKGROUND: Increased arterial stiffness is an independent risk factor for
      cardiovascular disease. The estrogen system (estrogen and estrogen receptor-alpha
      [ER-alpha]) has potent vasodilator and antiatherosclerotic activity in vascular
      tissue and therefore was implicated in the regulation of arterial stiffness. We
      hypothesized that the relationship between arterial stiffness and gene
      polymorphisms in ER-alpha has a sex-specific component in older humans. METHODS:
      Two hundred healthy older subjects, comprised of 85 men and 115 postmenopausal
      women (men, 66 +/- 5 years old; women, 64 +/- 7 years old; mean +/- SD)
      participated in a cross-sectional study. We determined the genotypes of single
      nucleotide polymorphisms (SNPs) at -401T/C of intron 1 and at 30T/C of exon 1 of
      ER-alpha, using a TaqMan-polymerase chain reaction method. Arterial stiffness was
      estimated by brachial-ankle pulse-wave velocity (baPWV). RESULTS: Polymorphisms
      of both -401T/C and 30T/C in ER-alpha affected baPWV values in postmenopausal
      women but did not affect men. The baPWV in women was significantly lower in the
      CC genotype at both -401T/C and 30T/C than in the TT genotype (both P < .05), and
      the CC genotype of two SNPs in women was significantly lower than in men.
      CONCLUSIONS: The present study suggests that the relationship between arterial
      stiffness and -401T/C or 30T/C polymorphisms in ER-alpha is different between
      sexes in older humans. These polymorphisms may be important in the health and
      clinical care of cardiovascular function and disease in older women.

PMID- 17531924
TI  - Beta2-adrenergic receptor gene polymorphisms and risk of ischemic stroke.
AB  - BACKGROUND: Beta2-adrenergic receptors (beta2-AR) mediate vasorelaxation in
      response to adrenergic agents. Genetic polymorphisms of beta2-AR were implicated
      in various cardiovascular and noncardiovascular traits. METHODS: We tested the
      role of the beta2AR-16 and beta2AR-27 gene variants in the susceptibility to the
      development of ischemic stroke in a genetically homogenous and clinically well
      characterized case-control sample that included 294 cases and 286 controls from
      Sardinia, Italy. This population was shown to be an optimal study sample for
      carrying out genetic analyses. RESULTS: Age, hypertension, dyslipidemia, and
      atrial fibrillation were independent risk factors for stroke in this cohort. We
      found that the presence of the Glu27 allelic variant was associated with a
      significantly increased risk of stroke when assuming a recessive mode of
      inheritance (odds ratio [OR], 1.68; 95% confidence interval [CI], 1.17-2.41; P =
      .005). The same results were obtained for the subgroup of ischemic strokes of
      arterial origin (n = 215): OR, 1.71; 95% CI, 1.14-2.57; P = .009. Furthermore,
      haplotype analysis confirmed that the presence of the Glu27 allele increased the
      risk of cerebrovascular accidents. CONCLUSIONS: Our data suggest that the Glu27
      allelic variant of the beta2-AR gene may be a determinant of ischemic stroke.

PMID- 17531925
TI  - Matrix metalloprotease activity is enhanced in the compensated but not in the
      decompensated phase of pressure overload hypertrophy.
AB  - BACKGROUND: During the transition of pressure overload hypertrophy (POH) to heart
      failure (HF) there is intense interstitial cardiac remodeling, characterized by a
      complex balance between collagen deposition and degradation by matrix
      metalloproteases (MMPs). This study was aimed at investigating the process of
      cardiac remodeling during the different phases of the transition of POH to HF.
      METHODS: Guinea pigs underwent thoracic descending aortic banding or sham
      operation. Twelve weeks after surgery, left-ventricular (LV) end-diastolic
      internal dimension and ventricular systolic pressure were measured by combined M
      mode echocardiography and micromanometer cathetherization. The MMP activity,
      tissue-specific MMP inhibitors (TIMPs), and collagen fraction were evaluated in
      LV tissue samples by zymography, ELISA, and computer-aided analysis,
      respectively. RESULTS: Banded animals were divided by lung weight values into
      either compensated left-ventricular hypertrophy (LVH) or HF groups, as compared
      with sham-operated controls. All HF animals exhibited a restrictive pattern of
      Doppler transmitral inflow, indicative of diastolic dysfunction, and developed
      lung congestion. Compensated LVH was associated with increased MMP-2 activity,
      which was blunted after transition to HF, at a time when TIMP-2 levels and
      collagen deposition were increased. CONCLUSIONS: The cardiac remodeling process
      that accompanies the development of POH is a phase-dependent process associated
      with progressive deterioration of cardiac function.

PMID- 17531926
TI  - Association of blood pressure and fitness with levels of atherosclerotic risk
      markers pre-exercise and post-exercise.
AB  - BACKGROUND: Physical fitness may attenuate the increased atherosclerotic risk in
      patients with systemic hypertension. We investigated the association of screening
      blood pressure (BP) and cardiorespiratory fitness with baseline levels and
      exercise-induced changes in levels of soluble atherosclerotic risk markers.
      METHODS: Twenty-six otherwise healthy and unmedicated subjects with elevated BP
      (systolic BP and/or diastolic BP > or =130/85 mm Hg) and 40 subjects with normal
      BP underwent 20-min treadmill exercise at 65% to 70% of predetermined peak oxygen
      consumption (VO(2peak)). Interleukin (IL)-6, soluble intercellular adhesion
      molecule (sICAM)-1, von Willebrand factor (VWF) antigen, and plasminogen
      activator inhibitor (PAI)-1 antigen were measured at baseline (ie, pre-exercise),
      early postexercise, and late postexercise (ie, 25 min after exercise). RESULTS:
      At baseline, higher screening mean arterial BP (MAP) independently predicted
      higher sICAM-1 levels (P = .031), and lower VO(2peak) independently predicted
      higher IL-6 (P = .016) and PAI-1 (P < .001) levels. Early and late postexercise
      lower VO(2peak) was associated with higher mean PAI-1 (P < or = .072) and IL-6 (P
      < or = .026) levels, and higher screening MAP was associated with higher mean
      sICAM-1 levels (P < or = .035). Higher VO(2peak) was associated with a greater
      PAI-1 increase from baseline to early postexercise in subjects with elevated BP
      (P = .045) but not in those with normal BP. CONCLUSIONS: Circulating levels of
      some atherosclerotic risk markers at baseline and with exercise were higher with
      elevated BP and lower with better fitness. Greater fitness did not particularly
      protect subjects with elevated BP from potentially harmful responses of
      atherosclerotic risk markers to acute physical exercise.

PMID- 17531927
TI  - Physical fitness and the relationship between hypertension and markers of
      atherothrombosis.

PMID- 17531928
TI  - Lack of association between serum uric acid and organ damage in a never-treated
      essential hypertensive population at low prevalence of hyperuricemia.
AB  - BACKGROUND: It is still undefined whether serum uric acid (SUA) is an independent
      risk factor for target organ damage (TOD) and cardiovascular events in human
      hypertension. We sought to investigate the association of SUA with subclinical
      cardiac, vascular, and renal alterations in never-treated uncomplicated essential
      hypertensives. METHODS: A total of 580 subjects with recently diagnosed (<1 year)
      grade 1 and 2 hypertension, categorized by sex and tertiles of SUA levels, were
      considered for this analysis. All subjects underwent extensive clinical,
      laboratory, and ultrasonographic investigations searching for cardiac and
      extracardiac TOD. RESULTS: Hyperuricemia (SUA >7.0 mg/dL in men and >6 mg/dL in
      women) was present in 8.3% of the patients. The overall prevalence of left
      ventricular hypertrophy (LVH), carotid alterations, and microalbuminuria was 28%,
      27%, and 8%, respectively. No differences in the prevalence rates of these TOD
      markers were present across all SUA tertiles in the entire population, as well as
      in both sexes. The SUA levels were similar in patients with and without LVH,
      carotid alterations, or microalbuminuria. When patients were classified according
      to the number of organs involved, those with multiple TOD (2 or 3 organs) had
      significantly higher SUA levels (5.1 +/- 1.3 or 5.2 +/- 1.4 mg/dL), as compared
      with those with a single or no organ involvement (4.9 +/- 1.3 or 4.9 +/- 1.4
      mg/dL, P < .05). The association, however, between SUA levels and multiple TOD
      was not confirmed in a logistic regression analysis. CONCLUSIONS: Our findings do
      not support the role of SUA as an independent risk factor for subclinical TOD in
      a selected population of recently diagnosed uncomplicated hypertensives at low
      prevalence of hyperuricemia.

PMID- 17531929
TI  - Effects of reduced uterine perfusion pressure on blood pressure and metabolic
      factors in pregnant rats.
AB  - BACKGROUND: Elements of metabolic syndrome (eg, dyslipidemia and impaired glucose
      metabolism) are often present in preeclamptic pregnancies. Currently it is
      unclear whether these metabolic aberrations presage preeclampsia, or if these
      manifestations result from placental ischemia and the ensuing proinflammatory
      state usually present in preeclampsia. METHODS: The present study employed
      chronic reductions in uterine perfusion pressure (RUPP) to generate a rat model
      of pregnancy-induced hypertension (PIH) for the evaluation of fasting plasma
      concentrations of triglycerides (TGs), glucose, resistin, insulin, and glucose
      tolerance in late-gestation rats. RESULTS: Mean arterial pressure was increased
      (130 +/- 2.1 mm Hg v 100 +/- 4.3 mm Hg; all values, mean +/- SEM), and fetal
      weight decreased (1.93 +/- 0.08 g v 2.19 +/- 0.06 g), in RUPP dams compared with
      normal pregnant (NP) control dams. Maternal fasting glucose (4.2 +/- 0.3 mmol L(
      1) v 3.1 +/- 0.4 mmol L(-1); P < .05) was increased in RUPP compared with NP
      dams. Serum TGs (2.62 +/- 0.29 mmol L(-1) v 2.45 +/- 0.51 mmol L(-1)), insulin
      (9.9 +/- 0.7 microU mL(-1) v 8.5 +/- 0.7 microU mL(-1)), resistin (46.25 +/- 4.19
      pg mL(-1) v 49.71 +/- 4.01 pg mL(-1)), and glucose area under the curve (650 +/-
      35 mmol min L(-1) v 570 +/- 34 mmol min L(-1)) were not different between the
      RUPP and NP dams. CONCLUSIONS: Although these findings do not rule out the
      hypothesis that preexisting symptoms of metabolic syndrome may contribute to the
      onset of preeclampsia, these data clearly show that pregnancy-induced
      hypertension resulting from RUPP does not elicit manifestations of metabolic
      syndrome in late-gestation rat dams.

PMID- 17531930
TI  - Sympathetic and renin-angiotensin systems contribute to increased blood pressure
      in sucrose-fed rats.
AB  - BACKGROUND: This study evaluated the effect of chronic sucrose feeding on
      hemodynamic parameters and renal sympathetic nervous activity. In addition,
      angiotensin I, II, and 1-7 levels were determined in plasma, heart, kidney, and
      the epididymal adipose tissue. METHODS: Male Wistar rats were treated for 30 days
      with 20% sucrose solution (n = 21) or tap water (n = 19) and food ad libitum.
      Blood pressure, cardiac output, and total peripheral resistance were recorded at
      the end of the 30-day treatment period. Sympathetic and angiotensinergic systems
      were evaluated by acute hexamethonium and captopril administration; plasma and
      tissue (heart, kidney, and epididymal adipose tissue) angiotensins were measured
      by high-performance liquid chromatography; and angiotensin-converting enzyme
      activity was determined by continuous fluorescent assay. Plasma renin activity
      and plasma levels of insulin and leptin were evaluated by radioimmunoassay.
      RESULTS: Chronic sucrose feeding was associated with increased blood pressure
      (BP) (129 +/- 1 v 102 +/- 3 mm Hg) and circulating insulin (171%) and leptin
      (356%) levels when compared with the control group. The sucrose group also showed
      a 27% higher renal sympathetic nervous activity. The depressor response to
      hexamethonium was similar in both groups, whereas captopril caused a more
      pronounced decrease in BP in the sucrose group than in controls (-40 +/- 2 v -11
      +/- 2 mm Hg), possibly reflecting the higher plasma renin activity and plasma
      content of angiotensin II and renal angiotensin II in sucrose rats. CONCLUSIONS:
      These findings suggest a specific renal renin-angiotensin-sympathetic activation
      as a potential mechanism for the cardiovascular changes in response to chronic
      sucrose feeding.

PMID- 17531931
TI  - Effects of "newer" and "older" antihypertensive drugs on hemorrheological,
      platelet, and endothelial factors. A substudy of the Anglo-Scandinavian Cardiac
      Outcomes Trial.
AB  - BACKGROUND: Different antihypertensive therapies may exert benefits via not only
      a reduction in blood pressure but also in improving the risk of thrombosis.
      METHODS: We tested the hypothesis that a more modern antihypertensive drug
      regimen (ie, amlodipine +/- perindopril) would have a more beneficial effect on
      hemorheological markers (white blood-cell count [WCC], plasma viscosity [PV],
      hematocrit [HCT], and fibrinogen)--and on plasma von Willebrand factor (vWf, an
      index of endothelial damage and dysfunction) and soluble P-selectin (sP-sel, an
      index of platelet activation), compared with an older antihypertensive drug
      regimen (ie, atenolol +/- bendroflumethiazide). RESULTS: After 6 months, PV, sP
      sel, and HCT fell in both groups (P < .01), while fibrinogen was unchanged.
      However, those 74 patients randomized to amlodipine +/- perindopril had
      significant reductions in WCC (P = .005), with no significant changes in vWF or
      platelet count. Conversely, in those 85 patients randomized to atenolol +/-
      bendroflumethiazide, there were significant reductions in vWF (P = .001) and
      platelet count (P = .011) but no significant reductions in WCC. There were no
      significant differences in the levels of any of the variables between the two
      arms of the trial, nor a significant difference in the magnitude of reduction
      between the two treatment arms. CONCLUSIONS: Within the constraints of this
      substudy design, there was no differential effect apparent of the two
      antihypertensive treatment arms on hemorheological parameters or endothelial and
      platelet function (as assessed by vWF and sP-sel), suggesting that other
      pathophysiological mechanisms may be involved.

PMID- 17531932
TI  - Blood-pressure categories in adolescence predict development of hypertension in
      accordance with the European guidelines.
AB  - BACKGROUND: It is estimated that by 2025, >1.5 billion adults worldwide will be
      hypertensive. Early identification of the population at risk would lead to
      improved utilization of preventive measures. We aimed to evaluate whether
      baseline body mass index (BMI) and blood-pressure (BP) values during adolescence
      (categorized according to the guidelines of the European Society of Hypertension
      European Society of Cardiology) are of use in predicting the development of
      hypertension in young adulthood. METHODS: The study population consisted of
      18,513 male regular army personnel who were initially recruited at 16.5 and 19
      years of age between 1976 and 1996. The main outcome was the percentage of
      subjects who developed hypertension (> or =140 systolic and > or =90 diastolic)
      at ages 26 to 45 years. RESULTS: At baseline, BP categories were: optimal, 5961
      (32.2%); normal, 7998 (43.2%); and high normal, 4554 (24.6%). Moreover, 1377
      (7.4%) were overweight (BMI 25-30 kg/m(2)), and 199 (1.1%) were obese (BMI >30
      kg/m(2)). At follow-up, 2277 (12.3%) subjects developed hypertension. The
      percentages progressing to hypertension were 9.46%, 11.99%, and 16.56% for
      optimal, normal, and high-normal categories, respectively (P < .01). Odds ratios
      (OR) for the development of hypertension in the normal and high-normal categories
      versus optimal were 1.30 (95% confidence interval [CI], 1.22-1.39) and 1.79 (95%
      CI, 1.67-1.93), respectively, adjusted for age and BMI. The ORs for hypertension
      in overweight and obese versus normal BMI were 1.75 (95% CI, 1.66-1.86) and 3.75
      (95% CI, 3.45-4.07), adjusted for age and BP. Of 9762 remaining at ideal BMI at
      follow-up, the percentages progressing to hypertension were 5.3%, 6.4%, and 9.5%
      for optimal, normal, and high normal (at baseline) (P < .01). CONCLUSIONS: The
      risk of developing hypertension in young adulthood may be predicted by BP
      categories and BMI at adolescence.

PMID- 17531933
TI  - Relation between insulin resistance and breast cancer among Chilean women.
AB  - PURPOSE: In Chile, diabetes and breast cancer are important public health
      problems. The association between insulin resistance and breast cancer, however,
      remains largely unexplored. METHODS: We conducted a case-control study to assess
      the relationship of insulin resistance (IR) and breast cancer in Chilean
      premenopausal and postmenopausal women. We compared 170 women, 33 to 86 years
      old, with incident breast cancer and 170 normal mammography controls, matched by
      5-year age interval. Plasmatic insulin and glucose were measured and IR was
      calculated by the homeostasis model assessment method. Anthropometric
      measurements and sociodemographic and behavioral data were also collected. Odds
      ratios (ORs) and 95% confidence intervals (CIs) were estimated by multivariable
      conditional logistic regression. RESULTS: IR was independently associated with
      breast cancer in postmenopausal women (OR = 2.70, 95%CI = 1.10-6.63), but not in
      premenopausal women (OR = 0.84, 95%CI = 0.20-3.52). Obesity was not associated
      with breast cancer at any age (OR = 0.68, 95%CI = 0.39-1.20). CONCLUSION: In this
      sample, IR increased the risk of breast cancer among postmenopausal women.

PMID- 17531934
TI  - Evidence-based practice.

PMID- 17531935
TI  - Bilateral spontaneous and simultaneous rupture of the Achilles tendons secondary
      to exercises for limb ischemia: a case report.
AB  - Exercise is proven to be safe and effective treatment and is prescribed routinely
      for the conservative management of intermittent claudication. Before advising
      about the exercises, the assessment of these patients rarely includes risk
      factors for the Achilles tendon rupture. We present a case report of bilateral
      simultaneous and spontaneous rupture of the Achilles tendons secondary to the
      exercises prescribed for intermittent claudication in a patient with significant
      risk factors for Achilles rupture.

PMID- 17531936
TI  - Isolated iatrogenic abdominal aortic dissection secondary to transfemoral
      arteriography: a case report.
AB  - Primary dissections of the abdominal aorta are rare and in most cases traumatic
      in origin. However, the natural history of isolated iatrogenic abdominal aortic
      dissection has not been well defined. This report describes a case of a 69-year
      old patient with iatrogenic dissection of the abdominal aorta after arteriography
      and delayed surgical approach.

PMID- 17531937
TI  - Smoking patterns, beliefs, and the practice of healthy behaviors in abstinent,
      relapsed, and recalcitrant smokers.
AB  - The purpose of this study was to perform a secondary analysis of smoking patterns
      and beliefs related to healthy behaviors in adult smokers (N = 71). Data for the
      secondary analysis were obtained from an original study that examined guided
      health imagery as a smoking cessation intervention. The imagery intervention
      resulted in significantly higher 2-year smoking abstinence rates for the
      intervention group of participants (26% vs. 12% for the control group). In this
      study, discriminant function analysis demonstrated that "well-established smoking
      patterns" accounted for 42% of the variance in those smokers who relapsed or
      never made any attempt to quit smoking. Higher baseline smoking rates, longer
      lifetime smoking histories, younger age at initiation of smoking, more positive
      beliefs about smoking (pros), and fewer healthy behaviors differentiated
      abstinent smokers from those who relapsed or were considered recalcitrant.
      Smoking patterns, belief systems related to smoking, and the practice of healthy
      behaviors need to be assessed as smokers enroll in cessation programs. Knowledge
      about relapsed and recalcitrant smokers will assist in the development of future
      interventions to meet smokers' unique needs and demands for cessation.

PMID- 17531938
TI  - Review of an article: Palareti G, Cosmi B, Legnani C, et al., for the PROLONG
      investigators. Therapy. N Engl J Med 2006;355:1780-1789.

PMID- 17531940
TI  - Clinical and immunopathologic findings in oral lichen planus pemphigoides.
AB  - Lichen planus pemphigoides (LPP) is a rare, acquired, immunobullous disorder of
      skin that occasionally involves oral mucous membranes. Clinical, histologic, and
      immunopathologic findings of the oral manifestations of LPP are described.
      Clinical features are lichenoid striae, erosions, and ulcerations involving
      gingiva and buccal mucosae. Histopathologic features are similar to those of ora
      lichen planus. Direct immunofluorescence demonstrates linear deposits of
      immunoglobulin G and complement component C3 along the basement membrane with
      fibrillar deposits of fibrin at the epithelial/lamina propria junction.
      Fluorescence overlay antigen mapping and laser scanning confocal microscopy of
      the biopsy specimen exhibits colocalization of in situ antibodies with beta4
      integrin, a marker of the keratinocyte basal plasma membrane and upper lamina
      lucida, consistent with the location of the bullous pemphigoid antigens. This
      case report describes a case of LPP that presented exclusively as an oral
      condition. Lichen planus pemphigoides should be considered in the clinical
      differential diagnosis of vesiculoerosive oral mucosal diseases.

PMID- 17531941
TI  - Rare oral cavity presentation of a B-cell lymphoblastic lymphoma. A case report
      and review of the literature.
AB  - Lymphoblastic lymphoma is an uncommon malignancy, with most cases showing a T
      cell phenotype and presenting as a mediastinal mass. By contrast, B-cell
      lymphoblastic lymphoma/leukemia is a rare high-grade malignancy that comprises
      approximately 10% of all lymphoblastic lymphomas. Lymphomas of the oral cavity
      are rare and typically present as intraosseous lesions that are most commonly
      diffuse large B-cell type. Here we present what we believe is the first B-cell
      lymphoblastic lymphoma initially presenting in the oral cavity. The case involves
      a 46-year-old white woman who presented with a mass in the right mandible. This
      report discusses this rare malignancy, including clinical presentation,
      histopathologic features, immunologic profile, treatment, and prognosis. This
      case emphasizes the importance of recognizing rare entities that may present in
      the oral cavity and the impact of the disease and its management.

PMID- 17531942
TI  - A case of carcinosarcoma arising in the submandibular gland.
AB  - A 54-year-old man presented with an 8-year history of a hard asymptomatic mass of
      the left submandibular area. Total excision of the left submandibular gland with
      radical neck dissection was performed under a diagnosis of a submandibular tumor,
      probably a malignant mixed tumor. The pathologic diagnosis was carcinosarcoma
      consisting of carcinomatous and sarcomatous elements. The epithelial component
      was composed of squamous cell carcinoma, undifferentiated carcinoma, and
      adenocarcinoma. The nonepithelial component was composed of chondrosarcoma,
      osteosarcoma, spindle cell sarcoma, rhabdomyosarcoma, and liposarcoma. In the
      central area of the tumor, a few remnants of benign pleomorphic adenoma were
      identifiable. The finding suggested that in our patient, the carcinosarcoma arose
      from a preexisting pleomorphic adenoma. In view of the expected aggressive nature
      of the tumor, the patient was treated with postoperative radiotherapy of 60 Gy
      total, in 30 daily fractions of 2 Gy, and chemotherapy. He currently remains well
      and free of disease 24 months after treatment.

PMID- 17531943
TI  - Clinical and imaging correlations of Treacher Collins syndrome: report of two
      cases.
AB  - Mandibulofacial dysostosis (Treacher Collins Syndrome) is an autosomal dominant
      genetic disorder that probably derives from inhibition of the facial structures
      from the first and second branchial arches. The facial pattern of the syndrome is
      a convex facial profile with a prominent nose above a retruded chin. The eyes are
      deformed by antimongoloid slant of the palpebral fissures and facial bones are
      hypoplastic. The alterations are caused by mutation in gene 5q32-33.1, which
      encodes the nucleolar phosphoprotein treacle. Computed tomography images are able
      to demonstrate craniofacial bones, allowing the morphological analysis of these
      bones in individuals with complex deformities. The purpose of this paper is to
      present the results of a clinical and computed tomography investigation of two
      patients with Treacher Collins syndrome.

PMID- 17531944
TI  - Modelling of flow processes of the structured two-phase disperse systems (solid
      phase-liquid medium).
AB  - A review of the basic theories and models of shear flow of suspensions is
      presented and the results of modeling of structured suspensions under flow
      conditions. The physical backgrounds and conditions of macroscopic discontinuity
      in the behaviour of high-concentrated systems are analyzed. The use of
      surfactants and imposed vibration for regulation of rheological properties of
      suspensions are considered. A review of the recent approaches and methods of
      computer simulation of concentrated suspensions is undertaken and results of
      computer simulation of suspensions are presented. Formation and destruction of
      the structure of suspension under static and dynamic conditions (including
      imposed combined shear and orthogonal oscillations) are discussed. The influence
      of interaction of particles as well as of some parameters characterizing a type
      and intensity of external perturbations on suspensions behavior is demonstrated.

PMID- 17531946
TI  - [Long-term outcome of the adult onset craniopharyngiomas].
AB  - There is few published series dealing on the long-term outcome of the adult-onset
      craniopharyngiomas. We report the long term clinical, tomodensitometric and MRI
      data outcome of 35 (23 woman and 12 men) consecutive adult-onset cured for
      craniopharyngiomas between 1983 and 2002, and followed-up in Rennes University
      Hospital. The operation was performed via frontopterional approach in 59% and
      transphenoidal approach in 41% of cases. Their age at the time of diagnosis was
      44.7+/-15.1 years (21-74). The average postoperation follow-up was 7.4+/-7.0
      years (0.1-19.1). Recurrence of tumour occurred in 8 patients (25.8%) and a tumor
      progression in 1 case. The delay of recurrence after initial surgery was 4.1+/
      1.3 years (1.4-6.3). Two patients had 5 and 6 years treatment by growth hormone
      (GH), without tumor recurrence. The observed increase of weight after the
      surgical cure of craniopharyngiomas concerned 22 patients (63%). The average
      weight gain was 17.5+/-14.7 kg (1.5-58). In 7 cases (20%) neuropsychological
      disorders were noted, of which 2 with lost of professional activity. Three
      patients died. In conclusion the craniopharyngiomas recurrence is frequent and
      can appear in very prolonged deadlines after the initial surgery.

PMID- 17531947
TI  - Unfolding transitions of Bacillus anthracis protective antigen.
AB  - Protective antigen (PA) is an 83kDa protein which, although essential for
      toxicity of Bacillus anthracis, is harmless and an effective vaccine component.
      In vivo it undergoes receptor binding, proteolysis, heptamerisation and membrane
      insertion. Here we probe the response of PA to denaturants, temperature and pH.
      We present analyses (including barycentric mean) of the unfolding and refolding
      behavior of PA and reveal the origin of two critical steps in the denaturant
      unfolding pathway in which the first step is a calcium and pH dependent
      rearrangement of domain 1. Thermal unfolding fits a single transition near 50
      degrees C. We show for the first time circular dichroism (CD) spectra of the
      heptameric, furin-cleaved PA63 and the low-pH forms of both PA83 and PA63.
      Although only PA63 should reach the acidic endosome, both PA83 and PA63 undergo
      similar acidic transitions and an unusual change from a beta II to a beta I CD
      spectrum.

PMID- 17531948
TI  - Destabilization of energy-metabolism oscillation in the absence of trehalose
      synthesis in the chemostat culture of yeast.
AB  - Energy-metabolism oscillation (EMO) in yeast is basically regulated by a feedback
      loop of redox reactions and modulated by the metabolism of storage carbohydrates
      like glycogen and trehalose. We found that EMO of the transformant tps1Delta
      deleted of TPS1 encoding trehalose-6-phosphate synthase fluctuated unsteadily
      with a short wavelength in the absence of trehalose synthesis, while EMO was
      gradually destabilized with the wavelength increasing as storage in a frozen
      state was prolonged. During EMO, whereas the fluctuations in levels of the oxygen
      uptake rate, NAD(P)H and cAMP were attenuated, the glycerol level fluctuated with
      high amplitude and the levels of glycogen and ethanol fluctuated with similar
      amplitudes to those in the wild type. Thus, EMO barely operated in tps1Delta
      depending on the increase of glycerol synthesis as a source of inorganic
      phosphate in place of trehalose synthesis and fairly conserved fluctuation in the
      level of ethanol as a synchronizing agent.

PMID- 17531949
TI  - Functional characterization of genetic variants of human FMO3 associated with
      trimethylaminuria.
AB  - Impaired conversion of trimethylamine to trimethylamine N-oxide by human flavin
      containing monooxygenase 3 (FMO3) is strongly associated with primary
      trimethylaminuria, also known as 'fish-odor' syndrome. Numerous non-synonymous
      mutations in FMO3 have been identified in patients suffering from this metabolic
      disorder (e.g., N61S, M66I, P153L, and R492W), but the molecular mechanism(s)
      underlying the functional deficit attributed to these alleles has not been
      elucidated. The purpose of the present study was to determine the impact of these
      disease-associated genetic variants on FMO3 holoenzyme formation and on steady
      state kinetic parameters for metabolism of several substrates, including
      trimethylamine. For comparative purposes, several common allelic variants not
      associated with primary trimethylaminuria (i.e., E158K, V257M, E308G, and the
      E158K/E308G haplotype) were also analyzed. When recombinantly expressed in insect
      cells, only the M66I and R492W mutants failed to incorporate/retain the FAD
      cofactor. Of the remaining mutant proteins P153L and N61S displayed substantially
      reduced (<10%) catalytic efficiencies for trimethylamine N-oxygenation relative
      to the wild-type enzyme. For N61S, reduced catalytic efficiency was solely a
      consequence of an increased K(m), whereas for P153L, both K(m) and k(cat) were
      altered. Similar results were obtained when benzydamine N-oxygenation was
      monitored. A homology model for FMO3 was constructed based on the crystal
      structure for yeast FMO which places the N61 residue alone, of the mutants
      analyzed here, in close proximity to the FAD catalytic center. These data
      demonstrate that primary trimethylaminuria is multifactorial in origin in that
      enzyme dysfunction can result from kinetic incompetencies as well as impaired
      assembly of holoprotein.

PMID- 17531950
TI  - Aggregation and hemi-fusion of anionic vesicles induced by the antimicrobial
      peptide cryptdin-4.
AB  - We show that cryptdin-4 (Crp4), an antimicrobial peptide found in mice, induces
      the aggregation and hemi-fusion of charged phospholipid vesicles constructed of
      the anionic lipid POPG and the zwitterionic lipid POPC. Hemi-fusion is confirmed
      with positive total lipid-mixing assay results, negative inner monolayer lipid
      mixing assay results, and negative results from contents-mixing assays.
      Aggregation, as quantified by absorbance and dynamic light scattering, is self
      limiting, creating finite-sized vesicle assemblies. The rate limiting step in the
      formation process is the mixing of juxtaposed membrane leaflets, which is
      regulated by bound peptide concentration as well as vesicle radius (with larger
      vesicles less prone to hemi-fusion). Bound peptide concentration is readily
      controlled by total peptide concentration and the fraction of anionic lipid in
      the vesicles. As little as 1% PEGylated lipid significantly reduces aggregate
      size by providing a steric barrier for membrane apposition. Finally, as stable
      hemi-fusion is a rare occurrence, we compare properties of Crp4 to those of many
      peptides known to induce complete fusion and lend insight into conditions
      necessary for this unusual type of membrane merger.

PMID- 17531951
TI  - The ergosterol biosynthesis inhibitor zaragozic acid promotes vacuolar
      degradation of the tryptophan permease Tat2p in yeast.
AB  - Ergosterol is the yeast functional equivalent of cholesterol in mammalian cells.
      Deletion of the ERG6 gene, which encodes an enzyme catalyzing a late step of
      ergosterol biosynthesis, impedes targeting of the tryptophan permease Tat2p to
      the plasma membrane, but does not promote vacuolar degradation. It is unknown
      whether similar features appear when other steps of ergosterol biogenesis are
      inhibited. We show herein that the ergosterol biosynthesis inhibitor zaragozic
      acid (ZA) evoked massive vacuolar degradation of Tat2p, accompanied by a decrease
      in tryptophan uptake. ZA inhibits squalene synthetase (SQS, EC 2.5.1.21), which
      catalyzes the first committed step in the formation of cholesterol/ergosterol.
      The degradation of Tat2p was dependent on the Rsp5p-mediated ubiquitination of
      Tat2p and was not suppressed by deletions of VPS1, VPS27, VPS45 or PEP12. We will
      discuss ZA-mediated Tat2p degradation in the context of lipid rafts.

PMID- 17531952
TI  - Thermodynamics imprinting reveals differential binding of metals to alpha
      synuclein: relevance to Parkinson's disease.
AB  - The aggregation of alpha-synuclein is a hallmark feature of Parkinson's disease
      (PD) and other synucleinopathies. Metals are the significant etiological factors
      in PD, and their interaction with alpha-synuclein affect dramatically the
      kinetics of fibrillation in vitro and are proposed to play an important and
      potential neurodegenerative role in vivo. In the present study, we investigated
      the stoichiometry of binding of copper [Cu (II)] and iron [Fe (III)] with alpha
      synuclein (wild recombinant type and A30P, A53T, E46K mutant forms) using
      isothermal titration calorimetry (ITC). alpha-Synuclein monomer (wild and mutant
      forms) titrated by Cu (II), showed two binding sites, with an apparent K(B) of
      10(5)M and 10(4)M, respectively. But, alpha-synuclein (wild type and mutant
      forms) titrated with Fe (III) revealed a K(B) of 10(5)M with single binding site.
      The present investigation uncovers the detailed binding propensities between
      metals and alpha-synuclein and has biological implications in PD.

PMID- 17531953
TI  - Influence of maternal lipid profile on placental protein expression of LDLr and
      SR-BI.
AB  - Maternal hyperlipidemia is a characteristic feature during pregnancy, it has been
      reported that modification of the maternal lipid profile can induce disturbance
      during pregnancy. In this study, we evaluated the impact of maternal lipid
      profile on the placental protein expression of two major receptors in cholesterol
      metabolism, the low density lipoprotein receptor (LDLr) and the scavenger
      receptor type B1 (SR-B1). We demonstrate an increase in the level of maternal
      total circulating cholesterol leads to a significant decrease in the level of the
      LDLr protein expression, while the level of the SR-BI expression remains
      unchanged. A similar change, for LDLr, is observed in association with the
      maternal pre-pregnancy body mass index and weight gain. Our data suggest that the
      LDLr plays a role in regulating cholesterol delivered to the baby from the
      placenta.

PMID- 17531954
TI  - The C. elegans homologue of the spastic paraplegia protein, spastin, disassembles
      microtubules.
AB  - Mutations in human spastin (SPG4) cause an autosomal dominant form of hereditary
      spastic paraplegia. Sequence analysis revealed that spastin contains the AAA
      (ATPases associated with diverse cellular activities) domain in the C-terminal
      region. Recently, it was reported that spastin interacts dynamically with
      microtubules and displays microtubule-severing activity. A plausible
      Caenorhabditis elegans homologue of spastin (SPAS-1) has been identified by
      homology search and phylogenetic analyses. To understand the function of the
      spastin homologue, we characterized the spas-1 deletion mutant and analyzed spas
      1 expression regulation in C. elegans. SPAS-1 was localized with cytoskeletons at
      the perinuclear region. We found that microtubules were intensely stained at the
      centrosomal region in the deletion mutant. Furthermore, overexpression of SPAS-1
      caused disassembly of microtubule network in cultured cells, while ATPase
      deficient SPAS-1 did not. These results indicate that C. elegans SPAS-1 plays an
      important role in microtubule dynamics. We also found that two kinds of products
      were generated from spas-1 by alternative splicing in a developmental stage
      dependent manner.

PMID- 17531955
TI  - The calcium-sensing receptor (CaR) is involved in strontium ranelate-induced
      osteoblast proliferation.
AB  - Strontium ranelate has several beneficial effects on bone and reduces the risk of
      vertebral and hip fractures in women with postmenopausal osteoporosis. We
      investigated whether Sr(2+) acts via a cell surface calcium-sensing receptor
      (CaR) in HEK293 cells stably transfected with the bovine CaR (HEK-CaR) and rat
      primary osteoblasts (POBs) expressing the CaR endogenously. Elevating Ca(o)(2+)
      or Sr(2+) concentration-dependently activated the CaR in HEK-CaR but not in non
      transfected cells, but the potency of Sr(2+) varied depending on the biological
      response tested. Sr(2+) was less potent than Ca(o)(2+) in stimulating inositol
      phosphate accumulation and in increasing Ca(i)(2+), but was comparable to
      Ca(o)(2+) in stimulating ERK phosphorylation and a non-selective cation channel,
      suggesting that Ca(2+) and Sr(2+) have differential effects on specific cellular
      processes. With physiological concentrations of Ca(o)(2+), Sr(2+)-induced further
      CaR activation. Neither Sr(2+) nor Ca(o)(2+) affected the four parameters just
      described in non-transfected cells. In POB, Sr(2+) stimulated cellular
      proliferation. This effect was CaR-mediated, as transfecting the cells with a
      dominant negative bovine CaR significantly attenuated Ca(o)(2+)-stimulated POB
      proliferation. Finally, Sr(2+) significantly increased the mRNA levels of the
      immediate early genes, c-fos and egr-1, which are involved in POB proliferation,
      and this effect was attenuated by overexpressing the dominant negative CaR. In
      conclusion, Sr(2+) is a full CaR agonist in HEK-CaR and POB, and, therefore, the
      anabolic effect of Sr(2+) on bone in vivo could be mediated, in part, by the CaR.

PMID- 17531956
TI  - Y1068 phosphorylation is the most sensitive target of disulfonated
      tetraphenylporphyrin-based photodynamic therapy on epidermal growth factor
      receptor.
AB  - Photodynamic therapy (PDT) is an anticancer therapy that utilizes the cytotoxic
      properties of a photosensitizer (PS) when combined with exposure to light.
      Photochemical internalization (PCI) is a drug delivery method for macromolecules
      based on PDT with endo-lysosomal localizing PSs, and synergistic effects can be
      obtained by PCI of EGFR targeting drugs. In this report the effects of PDT with
      two endo-lysosomal localizing PSs on EGFR are described. The experiments were
      performed in EGFR-positive cell-lines in vitro and also in a subcutaneous tumour
      model in mice. In PCI, the PSs are transported from the plasma membrane to
      endocytic vesicles by endocytosis and some of the PS can therefore be retained at
      the plasma membrane. Two distinct treatment conditions with different amounts of
      the PS on the plasma membrane were therefore studied in vitro. The expression of
      total and phosphorylated EGFR was analyzed on Western blots and EGF-binding to
      EGFR was evaluated by fluorescence microscopy of Alexa488-labelled EGF. The
      results showed that PDT, as utilized in PCI, caused inhibition of EGF-stimulated
      EGFR phosphorylation on Y1068 in NuTu-19 cells, but not in WiDr cells. PDT
      performed with more PS on the plasma membrane of NuTu-19 cells caused in addition
      inhibition of EGF binding and also lack of recognition by antibodies towards
      sequences in the intracellular domain of EGFR. In vivo, total EGFR was reduced
      24h after PDT in WiDr tumours. This report indicates EGF-stimulated
      phosphorylation on Y1068 as the most sensitive target on EGFR to PDT with
      amphiphilic PSs.

PMID- 17531957
TI  - Phospholipase A2 as targets for anti-cancer drugs.
AB  - Phospholipase A(2) (PLA(2)) are esterases that cleave glycerophospholipids to
      release fatty acids and lysophospholipids. Inhibition of PLA(2) alters cancer
      cell growth and death in vitro and PLA(2) expression is increased in breast,
      lung, and prostate cancers compared to control tissues. Thus, PLA(2) may be novel
      targets for chemotherapeutics. However, PLA(2) are a diverse family of enzymes,
      encompassing 19 members. The selectivity of these individual PLA(2) for
      phospholipids varies, as does their location within the cell, and tissue
      expression. Thus, their role in cancer may also vary. This review summarizes the
      expression of individual PLA(2) in cancers, focuses on the potential mechanisms
      by which these esterases mediate carcinogenesis, and suggests that select PLA(2)
      isoforms may be targets for anti-cancer drugs.

PMID- 17531959
TI  - Asymptomatic spontaneous cerebral emboli predict cognitive and functional decline
      in dementia.
AB  - BACKGROUND: Spontaneous cerebral emboli (SCE) are frequent in Alzheimer's disease
      (AD) and vascular dementia (VaD). We investigated the effect of SCE on the rates
      of cognitive and functional decline in AD and VaD. METHODS: One hundred thirty
      two patients with dementia (74 AD, National Institute of Neurological and
      Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders
      Association [NINCDS/ADRDA] criteria; 58 VaD, National Institute of Neurological
      Disorders and Stroke-Association Internationale pour la Recherche et
      l'Enseignement en Neurosciences [NINDS/AIREN] criteria) underwent 1-hour
      transcranial Doppler for detection of SCE (mean [SD] age 75.5 (7.4) years; 46%
      female). Neuropsychological tests (Mini-Mental State Examination [MMSE],
      Alzheimer's Disease Assessment Scale-Cognitive subscale [ADAS-Cog], and
      Neuropsychiatric Inventory [NPI]) and assessment of activities of daily living
      (Interview for Deterioration in Daily Living Activities in Dementia [IDDD]) were
      performed initially and 6 months later. SCE positive (SCE+ve, n = 47) and SCE
      negative (SCE-ve, n = 85) patients were compared using repeated measures analyses
      of variance (ANOVAs) adjusted for age, gender, and cardiovascular risk factors.
      RESULTS: SCE+ve patients with dementia, both AD and VaD, suffered a more rapid
      decline in cognitive functioning over 6 months (ADAS-cog, mean increase 7.1 for
      SCE+ve compared with 3.3 for SCE-ve, p = .006) and activities of daily living
      (IDDD, mean increase 24.4 for SCE+ve compared with 10.8 for SCE-ve, p = .014).
      CONCLUSIONS: Asymptomatic SCE are associated with an accelerated cognitive and
      functional decline in dementia. SCE may be a potentially treatable cause of
      disease progression in dementia.

PMID- 17531960
TI  - Regarding "Buprenorphine reduces alcohol drinking through activation of the
      nociceptin/orphanin FQ-NOP receptor system".

PMID- 17531962
TI  - Calsequestrin mutation and catecholaminergic polymorphic ventricular tachycardia:
      a simulation study of cellular mechanism.
AB  - OBJECTIVES: Patients with a missense mutation of the calsequestrin 2 gene (CASQ2)
      are at risk for catecholaminergic polymorphic ventricular tachycardia. This
      mutation (CASQ2(D307H)) results in decreased ability of CASQ2 to bind Ca2+ in the
      sarcoplasmic reticulum (SR). In this theoretical study, we investigate a
      potential mechanism by which CASQ2(D307H) manifests its pro-arrhythmic
      consequences in patients. METHODS: Using simulations in a model of the guinea pig
      ventricular myocyte, we investigate the mutation's effect on SR Ca2+ storage, the
      Ca2+ transient (CaT), and its indirect effect on ionic currents and membrane
      potential. We model the effects of isoproterenol (ISO) on Ca(V)1.2 (the L-type
      Ca2+ current, I(Ca(L))) and other targets of beta-adrenergic stimulation.
      RESULTS: ISO increases I(Ca(L)), prolonging action potential (AP) duration
      (Control: 172 ms, +ISO: 207 ms, at cycle length of 1500 ms) and increasing CaT
      (Control: 0.79 microM, +ISO: 1.61 microM). ISO increases I(Ca(L)) by reducing the
      fraction of channels which undergo voltage-dependent inactivation and increasing
      transitions from a non-conducting to conducting mode of channel gating.
      CASQ2(D307H) reduces SR storage capacity, thereby reducing the magnitude of CaT
      (Control: 0.79 microM, CASQ2(D307H): 0.52 microM, at cycle length of 1500 ms).
      The combined effect of CASQ2(D307H) and ISO elevates SR free Ca2+ at a rapid
      rate, leading to store-overload-induced Ca2+ release and delayed
      afterdepolarization (DAD). If resting membrane potential is sufficiently
      elevated, the Na+-Ca2+ exchange-driven DAD can trigger I(Na) and I(Ca(L))
      activation, generating a triggered arrhythmogenic AP. CONCLUSIONS: The
      CASQ2(D307H) mutation manifests its pro-arrhythmic consequences due to store
      overload-induced Ca2+ release and DAD formation due to excess free SR Ca2+
      following rapid pacing and beta-adrenergic stimulation.

PMID- 17531963
TI  - Protective effect of Operculina turpethum against 7,12-dimethyl benz(a)anthracene
      induced oxidative stress with reference to breast cancer in experimental rats.
AB  - Reactive oxygen species (ROS) directly or indirectly involves in multistage
      process of carcinogenesis. Antioxidant activity of methanolic extract of
      Operculina turpethum stems (MEOT) on 7,12 dimethylbenz(a)anthracene (DMBA)
      induced breast cancer was investigated in female Sprague-Dawley rats. Changes in
      the levels of lipid peroxidation and antioxidants system was evaluated in
      addition to tumour development. Twenty four female rats were divided into four
      groups: control, DMBA, DMBA+MEOT and MEOT. In the DMBA group, rats were
      intragastrically administered with 20 mg of DMBA using corn oil as vehicle.
      Animals of DMBA+MEOT group received a single dose of 20 mg of DMBA dissolved in
      corn oil intragastrically followed by O. turpethum extract (100 mg/kg body
      weight), while MEOT group received O. turpethum extract (100 mg/kg body weight)
      intragastrically daily for a period of 45 days. After the experimental period of
      45 days, oxidative stress parameters were assessed in serum, liver and breast of
      both control and experimental groups. In addition to this, tumour weight of
      breast was also assessed. A significant increase in lipid peroxidation levels
      were observed in the tested samples of cancer induced rats while the activities
      of enzymic antioxidants such as superoxide dismutase (SOD), catalase (CAT),
      glutathione peroxidase (GPx) and non-enzymic antioxidants like glutathione (GSH),
      ascorbic acid (Vitamin C) and alpha-tocopherol (Vitamin E) were decreased in
      cancer-bearing animals when compared to control animals. A significant (P<0.05)
      increase in the tumour weight was observed in the breast of DMBA group and the
      breast tumour weight decreased significantly (P<0.05) in the DMBA+MEOT groups.
      Oral administration of MEOT remarkably reduced the lipid peroxidation activity
      and increased the antioxidants level in drug treated animals and decreased the
      tumour weight significantly (P<0.05). This result suggests that MEOT shows
      antioxidant activity and play a protective role against DMBA induced breast
      cancer.

PMID- 17531964
TI  - Hydrophilic carotenoids: surface properties and aggregation of an astaxanthin
      lysine conjugate, a rigid, long-chain, highly unsaturated and highly water
      soluble tetracationic bolaamphiphile.
AB  - The surface and aggregation properties of a synthetic, highly water-soluble
      carotenoid, the tetracationic astaxanthin-lysine conjugate (Asly), have been
      examined through measurements of surface tension, optical absorption and dynamic
      light scattering. The following parameters were determined: critical aggregation
      concentration c(M), surface concentration Gamma, molecular area a(m), free energy
      of adsorption and aggregation (DeltaG(ad) degrees and DeltaG(M) degrees ,
      respectively), and the aggregate size r(H). The compound forms true monomolecular
      solutions in water below c(M); aggregates emerge only at rather high
      concentrations (> or =2.18 mM).

PMID- 17531965
TI  - Polymorphisms of cytochrome P450 1A1, glutathione S-transferase class mu, and
      tumour protein p53 genes and the risk of developing gallbladder cancer in
      Japanese.
AB  - OBJECTIVES: To examine the relationship between genetic polymorphisms of
      cytochrome P450 1A1 (CYP1A1), glutathione S-transferase class mu (GSTM1), and
      tumour protein p53 (TP53) genes, and gallbladder cancer (GBC) risk, a case
      control study was conducted. DESIGN AND METHODS: Genotypes of CYP1A1 T3801C,
      CYP1A1 Ile462Val, GSTM1, and TP53 Arg72Pro were determined in 54 cases of GBC and
      178 controls. RESULTS: The age-adjusted odds ratios (ORs) for the Ile/Val
      genotype of CYP1A1 Ile462Val polymorphism in women and the Arg/Pro genotype of
      TP53 Arg72Pro polymorphism in men were observed to be 2.70 (95% CI: 1.14-6.40)
      and 4.32 (95% CI: 1.08-17.2), respectively. No significant differences in the
      genotypic frequencies of CYP1A1 T3801C and GSTM1 polymorphisms were observed
      between controls and cases in both men and women. CONCLUSION: These results
      suggest that the Val allele of CYP1A1 Ile462Val polymorphism and the Pro allele
      of TP53 Arg72Pro polymorphism contribute to an increased risk of GBC among
      Japanese women and men, respectively.

PMID- 17531966
TI  - A web server for automatic analysis and extraction of relevant biological
      knowledge.
AB  - MOTIVATION: This application aims at assisting researchers with the extraction of
      significant medical and biological knowledge from data sets with complex
      relationships among their variables. RESULTS: Non-hypothesis-driven approaches
      like Principal Curves of Oriented Points (PCOP) are a very suitable method for
      this objective. PCOP allows for obtaining of a representative pattern from a huge
      quantity of data of independent variables in a very flexible and direct way. A
      web server has been designed to automatically realize 'non-linear pattern'
      analysis, 'hidden-variable-dependent' clustering, and new samples 'local
      dispersion-dependent' classification from the data involving new statistical
      techniques using the PCOP calculus. The tools facilitate the managing, comparison
      and visualization of results in a user-friendly graphical interface.
      AVAILABILITY: http://ibb.uab.es/revresearch.

PMID- 17531967
TI  - Calcium signaling in vertebrate embryonic patterning and morphogenesis.
AB  - Signaling pathways that rely on the controlled release and/or accumulation of
      calcium ions are important in a variety of developmental events in the vertebrate
      embryo, affecting cell fate specification and morphogenesis. One such major
      developmentally important pathway is the Wnt/calcium signaling pathway, which,
      through its antagonism of Wnt/beta-catenin signaling, appears to regulate the
      formation of the early embryonic organizer. In addition, the Wnt/calcium pathway
      shares components with another non-canonical Wnt pathway involved in planar cell
      polarity, suggesting that these two pathways form a loose network involved in
      polarized cell migratory movements that fashion the vertebrate body plan.
      Furthermore, left-right axis determination, neural induction and somite formation
      also display dynamic calcium release, which may be critical in these patterning
      events. Finally, we summarize recent evidence that propose a role for calcium
      signaling in stem cell biology and human developmental disorders.

PMID- 17531968
TI  - Hand2 determines the noradrenergic phenotype in the mouse sympathetic nervous
      system.
AB  - The basic helix-loop-helix (bHLH) transcription factor Hand2 has been shown to
      play a role in the development of the mammalian sympathetic nervous system (SNS);
      however, its precise role could not be uncovered because Hand2 is required for
      early embryonic survival. We therefore generated a conditional Hand2 knockout
      mouse line by excising Hand2 in Wnt1-Cre-expressing neural crest-derived cells.
      These mice die at 12.5 dpc with embryos showing severe cardiovascular and facial
      defects. Crest-derived cells, however, populate sites of SNS development and
      proliferate normally. Sympathetic precursors differentiate into neurons and
      express the pan-neuronal markers, beta3-tubulin (Tuj1) and Hu showing that Hand2
      is not essential for SNS neuronal differentiation. To determine whether Hand2
      regulates noradrenergic differentiation, the levels of the norepinephrine
      biosynthetic enzymes, tyrosine hydroxylase (TH) and dopamine beta-hydroxylase
      (DBH) was examined. Both enzymes were dramatically reduced in mutant embryos
      suggesting that the primary role of Hand2 in the SNS is determination of neuronal
      phenotype. Loss of Hand2 did not affect the expression of other members of the
      transcriptional circuit regulating SNS development, including Phox2a/b, Mash1 and
      Gata2/3; however, Hand2 was required for Hand1 expression. Our data suggest that
      the major role of Hand2 during SNS development is to permit sympathetic neurons
      to acquire a catecholaminergic phenotype.

PMID- 17531969
TI  - CREB activity modulates neural cell proliferation, midbrain-hindbrain
      organization and patterning in zebrafish.
AB  - Neural stem/progenitor cells (NPCs) self-renew and differentiate, generating
      neuronal and non-neuronal (glial) cell lineages. Although a number of factors,
      including transcription factors, have been shown to be important in the
      regulation of NPC proliferation and differentiation, the precise molecular
      networks remain to be identified. The cAMP Response Element-Binding protein
      (CREB) is a transcription factor important for neuronal survival, differentiation
      and plasticity. Recent work suggests that CREB activation, via serine
      phosphorylation in the kinase inducible domain, is important for neurogenesis in
      the adult rodent brain. We sought to further investigate CREB function in
      neurogenesis, using the zebrafish (Danio rerio). Structural and functional
      analysis of the zebrafish CREB orthologue showed high conservation with mammalian
      CREB. Activated (phosphorylated) CREB (pCREB) was localised to all known
      proliferation zones in the adult zebrafish brain, including actively cycling
      cells. Furthermore, we found that modulating CREB activity during early zebrafish
      development caused significant defects in neural proliferation, midbrain
      hindbrain organization and body patterning. These findings reveal broader and
      stage-specific physiological roles of CREB function during vertebrate neural
      development and proliferation.

PMID- 17531970
TI  - Multiple roles of Notch signaling in cochlear development.
AB  - Notch signaling inhibits hair cell differentiation, based on studies on mice
      deficient in Notch signaling-related genes and its downstream genes. However, the
      precise mechanisms of this inhibition are unknown because it is difficult to
      control the timing and duration of the suppression of Notch signaling. Here, we
      developed a novel in vitro culture and analysis method for mouse fetal cochleae
      and examined the roles of Notch signaling by its reversible inhibition through
      the use of Notch signaling inhibitors of gamma-secretase and TNF-alpha-converting
      enzyme. Notch inhibition with Notch signaling inhibitor treatment increases the
      number of cochlear hair cells, as observed in gene deletion experiments. We
      elucidated that this increase is regulated by the dichotomy between hair cells
      and supporting cells from common progenitors. We also propose other roles of
      Notch signaling in cochlear development. First, Notch signaling arrests the cell
      cycle of the cochlear epithelium containing putative hair cells and supporting
      cell progenitors because Notch inhibition with inhibitor treatment increases the
      number of 5-bromo-2'-deoxyuridine (BrdU)-positive cells that can differentiate
      into hair cells or supporting cells. Second, Notch signaling is required for the
      induction of Prox1-positive supporting cells. Third, Notch signaling is required
      for the maintenance of supporting cells.

PMID- 17531971
TI  - The effects of cholinergic stimulation and of nucleoside transport inhibition on
      spikes and spike patches in the canine small intestine in vivo.
AB  - Muscarinic agonists are known to enhance small intestinal contractions. A similar
      effect was also seen in pilot experiments with a nucleoside transport inhibitor.
      However, there is no information on their effects on the spatial pattern of
      action potential propagation. In an anesthetized, open-abdomen, canine (n=8)
      model, the propagation patterns of the slow wave and the ensuing action
      potentials (= spikes) were recorded before and during the i.v. administration of
      bethanechol or nucleoside transport inhibitor. Vehicle injections in 8 dogs
      served as controls. Electrical recordings were made using a 240-electrode array
      positioned on a 5-cm segment of the jejunum in situ. The incidence and the
      propagation of the action potentials were analyzed. Bethanechol dose-dependently
      increased the number of both longitudinally and circumferentially propagating
      spikes per slow wave. As during control, spikes in bethanechol propagated for a
      limited distance before terminating spontaneously, thereby exciting only a
      limited area (= patch). However, bethanechol did not change the size of the
      longitudinal spike patches (18.8+/-6.9 mm(2) at baseline and 25.0+/-18.6 mm(2) at
      0.5 mg/kg) nor of the circular spike patches (90.0+/-41.2 mm(2) at baseline and
      95.4+/-36.5 mm(2) at 0.5 mg/kg). The nucleoside transport inhibitor increased the
      occurrence of circular spikes in a step-wise fashion (>or=0.5 mg/kg). The size of
      the nucleoside transport inhibitor-induced circular spike patches (136.6+/-46.8
      mm(2)) was larger than those during baseline or muscarinic stimulation.
      Muscarinic agonists stimulate small intestinal contractility by inducing more
      action potentials, which in turn would trigger increased calcium release from
      intracellular stores. On the other hand, nucleoside transport inhibition enhances
      contractility by increasing both the number and the size of the circular spike
      patches.

PMID- 17531972
TI  - Mallory body formation is associated with epigenetic phenotypic change in
      hepatocytes in vivo.
AB  - Microarrays were done on the livers of mice fed DDC for 10 weeks, withdrawn 1
      month (DDC primed livers) and refed 6 days, and compared with mice fed the
      control diet. The expression of a large number of genes changed when DDC was fed
      or refed. A Venn diagram analysis identified 649 genes where gene expression was
      changed in the same direction. The epigenetic memory of the DDC primed liver
      involved an increase in the expression of ubiquitin D, alpha fetoprotein,
      connective tissue growth factor, integrin beta 2, DNA methyl transferase 3a and
      DNA damage-inducible 45 gamma. DNA methyl transferase 3b was down-regulated as
      was Cbp/p300. When DDC was refed, DNA methyltransferase and histone deacetylase
      were up-regulated as shown by microarray analysis. Histone3 lysine9 acetylation
      was increased by DDC and DDC refeeding and DNA methyltransferases were not
      changed as shown by Western blot analysis. The data suggest the concept that the
      epigenetic memory that explains why DDC primed hepatocytes form MBs in 7 days of
      DDC refeeding is primarily the result of epigenetic modifications of gene
      expression through changes in histone acetylation and methylation, as well as DNA
      methylation.

PMID- 17531973
TI  - From Mallory to Mallory-Denk bodies: what, how and why?
AB  - Frank B. Mallory described cytoplasmic hyaline inclusions in hepatocytes of
      patients with alcoholic hepatitis in 1911. These inclusions became known as
      Mallory bodies (MBs) and have since been associated with a variety of other liver
      diseases including non-alcoholic fatty liver disease. Helmut Denk and colleagues
      described the first animal model of MBs in 1975 that involves feeding mice
      griseofulvin. Since then, mouse models have been instrumental in helping
      understand the pathogenesis of MBs. Given the tremendous contributions made by
      Denk to the field, we propose renaming MBs as Mallory-Denk bodies (MDBs). The
      major constituents of MDBs include keratins 8 and 18 (K8/18), ubiquitin, and p62.
      The relevant proteins and cellular processes that contribute to MDB formation and
      accumulation include the type of chronic stress, the extent of stress-induced
      protein misfolding and consequent proteasome overload, a K8-greater-than-K18
      ratio, transamidation of K8 and other proteins, presence of p62 and autophagy.
      Although it remains unclear whether MDBs serve a bystander, protective or injury
      promoting function, they do serve an important role as histological and potential
      progression markers in several liver diseases.

PMID- 17531974
TI  - Pathology of damaging electrical stimulation in the retina.
AB  - The goal of this study was to examine the characteristics of electrically induced
      retinal damage. A retinal prosthesis must be both effective and safe, but most
      research related to electrical stimulation of the retina has involved measures of
      efficacy (for example, stimulus threshold), while relatively little research has
      investigated the safety of electrical stimulation. In this study, a single
      platinum microelectrode was inserted into the vitreous cavity of normally-sighted
      adult Long Evans pigmented rats. In one group of animals, no contact was made
      between the electrode and the retina and current pulses of 0.05 (n=3) and 0.2
      (n=6) microC/phase were applied. In a second group, visible contact (slight
      dimpling of the retina) was made between the electrode and the retina and current
      pulses of 0.09 (n=4) microC/phase were applied. In both cases, stimulus pulses
      (biphasic, cathodic first, 1 ms/phase) were applied for 1 h at 100 Hz. Also,
      control experiments were run with no electrical stimulation with retina contact
      (n=4) and with no retinal contact (n=3). After stimulation, the animal was
      survived for 2 weeks with ocular photography and electroretinography (ERG) to
      document changes. During the follow-up period, retinal changes were observed only
      when the electrode contacted the retina, with or without electrical stimulation.
      No difference was noted in ERG amplitude or latency comparing the test eye to the
      stimulated eye. Histological analysis was performed after sacrifice at 2 weeks. A
      semi-quantitative method for grading 18 features of retina/RPE/choroidal
      appearance was established and integer grades applied to both test and control
      eyes. Using this method and comparing the most severely affected area (highest
      grade), significant differences (p<0.05) were noted between experiments with
      retinal contact and without retinal contact in all features except inner nuclear
      layer thickness. No difference was noted within a group based on the intensity of
      electrical stimulus applied. The size of the affected area was significantly
      larger with both retinal contact and electrical stimulation compared to with
      retinal contact alone. We conclude that mechanical pressure alone and mechanical
      pressure with excessive electrical stimulation causes damage to the retina but
      that electrical stimulation coupled with mechanical pressure increases the area
      of the damage.

PMID- 17531975
TI  - Schistosoma mansoni: germ-line transformation approaches and actin-promoter
      analysis.
AB  - Towards germ-line transformation miracidia were biolistically transformed with
      GFP reporter gene constructs and successfully reintroduced into the schistosome
      cycle. By PCR and confocal microscopy the presence and the expression of GFP were
      confirmed in cercariae or adults of the F(0) and F(1) generations. This indicated
      the presence of the constructs in the germ-line, although no evidence for genome
      integration was obtained. About 3kb of 5' upstream sequences of the actin gene
      SmAct1 were identified by in silico analyses, and different fragments up to 1.5kb
      subcloned for GFP-vector construction. A 445bp fragment was sufficient for
      transcription initiation in larvae or adults as confirmed by confocal microscopy.
      An actin gene characteristic assembly of TATA, CArG, and CAAT boxes has been
      identified, which seems to be functionally conserved between vertebrates and
      invertebrates. However, a vertebrate-specific intron containing an additional
      regulatory CArG box was not found indicating that the regulation of SmAct1
      transcription depends exclusively on its promoter region.

PMID- 17531976
TI  - dXNP, a Drosophila homolog of XNP/ATRX, induces apoptosis via Jun-N-terminal
      kinase activation.
AB  - XNP/ATRX, a causative gene of X-linked alpha-thalassemia/mental retardation
      syndrome, encodes an SNF2 family ATPase/helicase protein. To better understand
      the role of XNP/ATRX in development, we isolated and characterized a Drosophila
      XNP/ATRX homolog, dXNP, which contains highly conserved SNF2 and helicase
      domains. Ectopically expressed dXNP induced strong apoptosis in the developing
      eye and wing, but did not affect cell cycle progression or the expression of
      wingless and engrailed, essential regulators of development. The dXNP-induced
      apoptosis was strongly suppressed by DJNKK/hemipterous mutation, and dXNP
      increased JNK activity. Taken together, these results suggest that dXNP regulates
      apoptosis via JNK activation.

PMID- 17531977
TI  - Equine lysozyme: the molecular basis of folding, self-assembly and innate amyloid
      toxicity.
AB  - Calcium-binding equine lysozyme (EL) combines the structural and folding
      properties of c-type lysozymes and alpha-lactalbumins, connecting these two most
      studied subfamilies. The structural insight into its native and partially folded
      states is particularly illuminating in revealing the general principles of
      protein folding, amyloid formation and its inhibition. Among lysozymes EL forms
      one of the most stable molten globules and shows the most uncooperative refolding
      kinetics. Its partially-folded states serve as precursors for calcium-dependent
      self-assembly into ring-shaped and linear amyloids. The innate amyloid
      cytotoxicity of the ubiquitous lysozyme highlights the universality of this
      phenomenon and necessitates stringent measures for its prevention.

PMID- 17531978
TI  - Ripply2 is essential for precise somite formation during mouse early development.
AB  - The regions of expression of Ripply1 and Ripply2, presumptive transcriptional
      corepressors, overlap at the presomitic mesoderm during somitogenesis in mouse
      and zebrafish. Ripply1 is required for somite segmentation in zebrafish, but the
      developmental role of Ripply2 remains unclear in both species. Here, we generated
      Ripply2 knock-out mice to investigate the role of Ripply2. Defects in
      segmentation of the axial skeleton were observed in the homozygous mutant mice.
      Moreover, somite segmentation and expression of Notch2 and Uncx4.1 were
      disrupted. These findings indicate that Ripply2 is involved in somite
      segmentation and establishment of rostrocaudal polarity.

PMID- 17531979
TI  - Competitive inhibition of glutamate dehydrogenase reaction.
AB  - Irrespective of their pyridine nucleotide specificity, all glutamate
      dehydrogenases share a common chemical mechanism that involves an enzyme bound
      'iminoglutarate' intermediate. Three compounds, structurally related to this
      intermediate, were tested for the inhibition of purified NADP-glutamate
      dehydrogenases from two Aspergilli, as also the bovine liver NAD(P)-glutamate
      dehydrogenase. 2-Methyleneglutarate, closely resembling iminoglutarate, was a
      potent competitive inhibitor of the glutamate dehydrogenase reaction. This is the
      first report of a non-aromatic structure with a better glutamate dehydrogenase
      inhibitory potency than aryl carboxylic acids such as isophthalate. A suitably
      located 2-methylene group to mimic the iminium ion could be exploited to design
      inhibitors of other amino acid dehydrogenases.

PMID- 17531980
TI  - SREBP-1c mediates the retinoid-dependent increase in fatty acid synthase promoter
      activity in HepG2.
AB  - Treatment of HepG2 with all-trans retinoic acid (RA) induces expression of fatty
      acid synthase (FAS) mRNA and protein. Transfections show that the FAS promoter
      positively responds to retinoid X receptor (RXR) but not to RA receptor (RAR)
      agonists. Since RXR alone is capable of mediating the RA response of FAS, the
      existence of a classical RA-responsive element in the FAS promoter may be ruled
      out. Binding sites for NF-Y and SREBP-1 proved to be essential for the RA
      response. Exposure to all-trans RA increased mRNA and protein levels of SREBP-1,
      a transcriptional activator for FAS. Overexpression of a dominant-negative form
      of SREBP-1c diminished the RA-dependent increase in promoter activity. These data
      demonstrate that RXR ligands can stimulate the expression of a lipogenic gene
      solely by inducing transcription and cleavage of membrane-bound SREBP-1c.

PMID- 17531981
TI  - Network analysis of protein dynamics.
AB  - The network paradigm is increasingly used to describe the topology and dynamics
      of complex systems. Here, we review the results of the topological analysis of
      protein structures as molecular networks describing their small-world character,
      and the role of hubs and central network elements in governing enzyme activity,
      allosteric regulation, protein motor function, signal transduction and protein
      stability. We summarize available data how central network elements are enriched
      in active centers and ligand binding sites directing the dynamics of the entire
      protein. We assess the feasibility of conformational and energy networks to
      simplify the vast complexity of rugged energy landscapes and to predict protein
      folding and dynamics. Finally, we suggest that modular analysis, novel centrality
      measures, hierarchical representation of networks and the analysis of network
      dynamics will soon lead to an expansion of this field.

PMID- 17531982
TI  - The relation between solution association and surface activity of the hydrophobin
      HFBI from Trichoderma reesei.
AB  - Hydrophobins are small fungal surface active proteins that self-assemble at
      interfaces into films with nanoscale structures. The hydrophobin HFBI from
      Trichoderma reesei has been shown to associate in solution into tetramers but the
      role of this association on the function of HFBI has remained unclear. We
      produced two HFBI variants that showed a significant shift in solution
      association equilibrium towards the tetramer state. However, this enhanced
      solution association did not alter the surface properties of the variant HFBIs.
      The results show that there is not a strong relationship between HFBI solution
      association state and surface properties such as surface activity.

PMID- 17531983
TI  - Enhanced biological activity of polymeric osteopontin.
AB  - Osteopontin is a multifunctional glycoprotein with roles in immunomodulation,
      inflammatory response, tissue mineralization, and tissue remodeling, which are
      mediated primarily through integrins. Transglutaminase 2 selectively cross-links
      proteins by isopeptide bonding. Osteopontin is one of the substrates of this
      enzyme and undergoes polymerization; however, the biological meaning of this
      polymerization remains unknown. Using recombinant osteopontin polymerized with
      purified transglutaminase 2, we examined cell adhesion, spreading, focal contact
      formation, and migration of SW480 or HUVE cells. All of these cellular behaviors
      were dramatically enhanced with polymeric osteopontin. These enhancements of
      cellular functions imply that polymerization might modulate physiological and
      pathological functions of osteopontin.

PMID- 17531984
TI  - The neurobiology of love.
AB  - Romantic and maternal love are highly rewarding experiences. Both are linked to
      the perpetuation of the species and therefore have a closely linked biological
      function of crucial evolutionary importance. The newly developed ability to study
      the neural correlates of subjective mental states with brain imaging techniques
      has allowed neurobiologists to learn something about the neural bases of both
      romantic and maternal love. Both types of attachment activate regions specific to
      each, as well as overlapping regions in the brain's reward system that coincide
      with areas rich in oxytocin and vasopressin receptors. Both deactivate a common
      set of regions associated with negative emotions, social judgment and
      'mentalizing' that is, the assessment of other people's intentions and emotions.
      Human attachment seems therefore to employ a push-pull mechanism that overcomes
      social distance by deactivating networks used for critical social assessment and
      negative emotions, while it bonds individuals through the involvement of the
      reward circuitry, explaining the power of love to motivate and exhilarate. Yet
      the biological study of love, and especially romantic love, must go beyond and
      look for biological insights that can be derived from studying the world
      literature of love, and thus bring the output of the humanities into its orbit.

PMID- 17531985
TI  - mRNA quality control: an ancient machinery recognizes and degrades mRNAs with
      nonsense codons.
AB  - Nonsense-mediated mRNA decay (NMD) is an mRNA surveillance pathway which ensures
      the rapid degradation of mRNAs containing premature translation termination
      codons (PTCs or nonsense codons), thereby preventing the accumulation of
      truncated and potentially harmful proteins. In this way, the NMD pathway
      contributes to suppressing or exacerbating the clinical manifestations of
      specific human genetic disorders. Studies in model organisms have led to the
      identification of the effectors of the NMD pathway, and illuminated the
      mechanisms by which premature stops are discriminated from natural stops, so that
      only the former trigger rapid mRNA degradation. These studies are providing
      important insights that will aid the development of new treatments for at least
      some human genetic diseases.

PMID- 17531986
TI  - Legionella pneumophila adaptation to intracellular life and the host response:
      clues from genomics and transcriptomics.
AB  - Legionella pneumophila is the causative agent of the pneumonia-like Legionnaires'
      disease. The bacterium's survival and spread depend on the ability to replicate
      inside eukaryotic phagocytic cells. A particular feature of Legionella is its
      dual host system allowing the intracellular growth in protozoa like Acanthamoeba
      castellanii, and during infection in human alveolar macrophages. Genome analysis
      and comparisons as well as expression profiling of the pathogen and the host
      helped to identify regulatory circuits mediating adaptation of the L. pneumophila
      transcriptome to the intracellular environment and gave clues for the metabolic
      needs of intracellular Legionella. This review will summarize what is currently
      known about intracellular gene expression of L. pneumophila, the transcriptional
      host response of the model host Dictyostelium discoideum and will present
      hypotheses drawn from these data with respect to subversion of host cell
      functions and virulence of L. pneumophila.

PMID- 17531987
TI  - Collagen matrix deposition is dramatically enhanced in vitro when crowded with
      charged macromolecules: the biological relevance of the excluded volume effect.
AB  - The excluded volume effect (EVE) rules all life processes. It is created by
      macromolecules that occupy a given volume thereby confining other molecules to
      the remaining space with large consequences on reaction kinetics and molecular
      assembly. Implementing EVE in fibroblast culture accelerated conversion of
      procollagen to collagen by procollagen C-proteinase (PCP/BMP-1) and proteolytic
      modification of its allosteric regulator, PCOLCE1. This led to a 20-30- and 3-6
      fold increased collagen deposition in two- and three-dimensional cultures,
      respectively, and creation of crosslinked collagen footprints beneath cells.
      Important parameters correlating with accelerated deposition were hydrodynamic
      radius of macromolecules and their negative charge density.

PMID- 17531988
TI  - Mitochondrial gene expression in granulosa cells of severe endometriosis with in
      vitro fertilization and embryo transfer.
AB  - The expression of mitochondrial genes in granulosa cells was quantitated by real
      time polymerase chain reaction. The expression ratio of mitochondrial genes in
      granulosa cells of patients with severe endometriosis showed no statistically
      significant difference compared with cases of tubal infertility without
      endometriosis.

PMID- 17531989
TI  - Ovarian response and pregnancy outcome in poor-responder women: a randomized
      controlled trial on the effect of luteinizing hormone supplementation on in vitro
      fertilization cycles.
AB  - OBJECTIVE: To prospectively assess the effect of using a combination of
      recombinant follicle-stimulating hormone (rFSH) and recombinant luteinizing
      hormone (rLH) on ovarian stimulation parameters and treatment outcome among poor
      responder patients. DESIGN: Prospective randomized trial. SETTING: University
      associated private medical center. PATIENT(S): Eighty-four patients who had a
      basal FSH level of >or=10 mIU/mL, who were >or=40 years of age, and who were
      undergoing their first IVF cycle participated in this controlled trial.
      INTERVENTION(S): Patients were randomly allocated into two study groups: group A,
      in which ovarian stimulation included GnRH analogue and rFSH and rLH, and group
      B, in which patients received GnRH analogue and rFSH without further LH addition.
      MAIN OUTCOME MEASURE(S): Primary outcome measures included the ongoing pregnancy
      rate per retrieval and implantation rate per embryo transferred. The number of
      days of gonadotropin treatment, E(2) level on rHCG administration day, number of
      developed follicles, number of retrieved oocytes, number of normally fertilized
      zygotes (at the two-pronuclear [2PN] stage), cumulative embryo score, and number
      of transferred embryos were also evaluated. RESULT(S): The overall pregnancy rate
      was 22.61% (19 pregnancies among 84 couples). The pregnancy wastage rate was
      30.00% in group A and 22.22% in group B. There were no differences in either
      primary or secondary end points. CONCLUSION(S): The results of this prospective
      and randomized trial show that the addition of rLH at a given time of follicular
      development produces no further benefit in the patient population of our study. A
      reduced ovarian response cannot be overcome by changes in the stimulation
      protocol.

PMID- 17531990
TI  - Decreased human leukocyte antigen-DR expression in the lipid raft by peritoneal
      macrophages from women with endometriosis.
AB  - OBJECTIVE: To investigate the macrophage response in endometriosis by determining
      the expression and localization of human leukocyte antigen (HLA)-ABC and HLA-DR
      by the peritoneal fluid (PF) macrophages and PF concentrations of interferon
      (IFN)-gamma that regulate HLA expression. DESIGN: Case-control study. SETTING:
      University hospital. PATIENT(S): 64 Japanese endometriosis patients, and 65 women
      with other laparoscopic diagnoses. INTERVENTION(S): Venipuncture and laparoscopic
      peritoneal fluid collection. MAIN OUTCOME MEASURE(S): Expression and localization
      of HLA-ABC and HLA-DR in PF macrophages were determined by flow cytometry and
      confocal microscopy. The concentration of IFN-gamma in PF was determined by
      enzyme-linked immunosorbent assay. RESULT(S): In women with endometriosis,
      expression of HLA-ABC and HLA-DR by PF macrophages, and the IFN-gamma
      concentrations in PF were statistically significantly lower than in controls.
      Women with endometriosis showed a statistically significant positive correlation
      between HLA expression and IFN-gamma concentration. By confocal microscopy, HLA
      ABC was distributed homogenously on the macrophage surface whereas HLA-DR
      expression on these cells corresponded to the lipid raft. CONCLUSION(S): In women
      with endometriosis, low HLA expression and particularly reduced HLA-DR in the
      lipid raft may be influenced by low IFN-gamma and may compromise antigen
      presentation, limiting the immune response to peritoneal cavity antigens such as
      implanted or metaplastic endometrial tissue.

PMID- 17531991
TI  - Dydrogesterone increases allopregnanolone in selected brain areas and in serum of
      female rats.
AB  - OBJECTIVE: To investigate the effects of dydrogesterone (DYD), a synthetic
      progestin largely used in hormone therapy, on the central nervous system by
      studying two markers of the neuroendocrine function: the neurosteroid
      allopregnanolone and the opioid beta-endorphin. DESIGN: Experimental study on
      animal model. SETTING: Academic research environment. ANIMAL(S): 72 Wistar female
      rats. INTERVENTION(S): One group of fertile and one of ovariectomized rats
      (receiving placebo) were used as control. After ovariectomy, the rats underwent a
      2-week oral treatment of DYD (0.2, 0.6, or 1.0 mg/kg per day), alone or with
      estradiol valerate (E2V; 0.05 mg/kg per day). MAIN OUTCOME MEASURE(S):
      Allopregnanolone and beta-endorphin, assessed in different brain areas and in
      circulation. RESULT(S): Ovariectomy decreased allopregnanolone anywhere except in
      the adrenal gland and reduced beta-endorphin central levels; E2V reversed the
      effects of ovariectomy; and DYD (1 mg/kg per day) increased allopregnanolone
      levels in frontal lobe, hippocampus, and hypothalamus. Combined administration of
      DYD at 1 mg/kg per day plus E2V determined a further increase of allopregnanolone
      levels in frontal lobe, hippocampus, hypothalamus, and serum. Dydrogesterone did
      not modify the levels of beta-endorphin induced by E2V. CONCLUSION(S):
      Dydrogesterone interacts with allopregnanolone levels (less with beta-endorphin),
      and it can be considered important modulator of the neuroendocrine function.

PMID- 17531992
TI  - Open-identity donor insemination in the United States: is it on the rise?
AB  - Information about US donor insemination programs was reviewed to determine
      whether an increasing number are offering open-identity donation. Results
      indicate that indeed, numbers are rising and that the ratio of open-identity to
      anonymous sperm donors in a program increases the longer that the program has
      offered an open-identity option.

PMID- 17531993
TI  - Chronic endometritis: correlation among hysteroscopic, histologic, and
      bacteriologic findings in a prospective trial with 2190 consecutive office
      hysteroscopies.
AB  - OBJECTIVE: To evaluate the type and etiopathogenic role of infectious agents
      detected in endometrial cultures obtained from women with chronic endometritis
      (CE). DESIGN: Prospective controlled study. SETTING: University hospital.
      PATIENT(S): 2190 women undergoing hysteroscopy for different indications.
      INTERVENTION(S): Vaginal and endometrial samples were collected from 438 women
      with a CE diagnosis at hysteroscopy and 100 women with no signs of CE (controls).
      MAIN OUTCOME MEASURE(S): Histology and cultures for common bacteria, Neisseria
      gonorrhoeae and Mycoplasma, and molecular biology testing for Chlamydia were
      performed. RESULT(S): We compared results of vaginal and intrauterine cultures
      obtained from women with and without CE. Histologic results were positive in 388
      of these cases (88.6%), and at least one microorganism was found in 320
      endometrial samples (73.1%). In the control group, histologic results and
      endometrial culture were positive in only 6% and 5% of cases, respectively. The
      most frequent infectious agents detected at the endometrial level were common
      bacteria (58% of cases). Ureaplasma urealyticum was detected in 10% and Chlamydia
      in only 2.7% of positive endometrial cultures. In only 143 (32.6%) cases were the
      same infectious agent isolated in endometrial and vaginal cultures.
      CONCLUSION(S): More than 70% of CE cases resulted from nongonococcal,
      nonchlamydial infections. Common bacteria and Mycoplasma were the most frequent
      etiologic agents. Vaginal cultures have low concordance with endometrial
      cultures.

PMID- 17531994
TI  - Fertility after bilateral uterine artery embolization in a sheep model.
AB  - OBJECTIVE: To evaluate the impact of bilateral uterine artery embolization (UAE)
      upon fertility in sheep. DESIGN: Prospective study. SETTING: University-based
      interventional radiology, pathology, and reproductive physiology units.
      ANIMAL(S): Nineteen control ewes, 10 ewes embolized with polyvinyl alcohol
      particles (PVA group), and 10 ewes embolized with Tris-acryl gelatin microspheres
      (TGMS group). INTERVENTION(S): Bilateral UAE was performed with 600- to 1,000-mum
      PVA particles or 700- to 900-mum TGMS particles. Animals of three groups were
      synchronized and naturally inseminated. MAIN OUTCOME MEASURE(S): For each ewe, a
      hormonal follow-up was performed throughout the gestation. Gestation duration,
      number and weight of newborns, and fertility and gestation rates were recorded.
      RESULT(S): Mean number of estrus before insemination and gestation duration were
      not different between groups. There were 47 living newborns: 26 control, 9 PVA,
      and 12 TGMS. Overall birth weight of newborns was 3.7 +/- 0.9 kg for controls,
      3.6 +/- 1.1 kg for TGMS, and 2.2 +/- 0.7 kg for PVA (which was statistically
      significant vs. control). In the PVA group, there was a statistically significant
      decrease of fertility rate and gestation rate vs. controls, but this was not the
      case in the TGMS group. CONCLUSION(S): Particles of PVA decrease fertility in
      sheep and lead to intrauterine growth retardation.

PMID- 17531995
TI  - Programmatic implementation of blastocyst transfer in a university-based in vitro
      fertilization clinic: maximizing pregnancy rates and minimizing triplet rates.
AB  - To assess whether the use of extended embryo culture can reduce the incidence of
      high-order multiple gestations, a retrospective analysis of 7,418 fresh ETs
      performed in a university-based IVF clinic from 1997-2003 was conducted,
      comparing program results before and after institution of a protocol to select
      patients for extended culture of in vitro fertilized embryos. The incidence of
      triplet pregnancies was significantly reduced in patients at highest risk for
      high-order multiple gestations, i.e., those at <35 years of age (16.8% versus
      6.8%), those at 35-37 years of age (13.0% versus 5.6%), and recipients of donated
      oocytes (11.2% versus 4.5%).

PMID- 17531996
TI  - Androgen receptor expression and morphology of forebrain and neuromuscular
      systems in male green anoles displaying individual differences in sexual
      behavior.
AB  - Investigating individual differences in sexual performance in unmanipulated males
      is important for understanding natural relationships between behavior and
      morphology, and the mechanisms regulating them. Among male green anole lizards,
      some court and copulate frequently (studs) and others do not (duds). To evaluate
      potential factors underlying differences in the level of these behaviors,
      morphology and androgen receptor expression in neuromuscular courtship and
      copulatory structures, as well as in the preoptic area and amygdala, were
      compared in males displaying varying degrees of sexual function. This study
      revealed that individual differences in behavior among unmanipulated males, in
      particular the extension of a throat fan (dewlap) used during courtship, were
      positively correlated with the size of fibers in the associated muscle and with
      soma size in the amygdala. The physiological response to testosterone, as
      indicated by the height of cells in an androgen-sensitive portion of the kidney,
      was also correlated with male sexual behavior, and predicted it better than
      plasma androgen levels. Androgen receptor expression was not related to the
      display of courtship or copulation in any of the tissues examined. The present
      data indicate that higher levels of male courtship behavior result in (or are the
      result of) enhanced courtship muscle and amygdala morphology, and that androgen
      sensitive tissue in studs may be more responsive to testosterone than duds.
      However, some mechanism(s) other than androgen receptor expression likely confer
      this difference in responsiveness.

PMID- 17531997
TI  - Structure-function properties of the apoE-dependent COX-2 pathway in vascular
      smooth muscle cells.
AB  - Apolipoprotein (apoE) E is a multifunctional protein that plays a critical role
      in atherogenesis, in part by regulating the intimal proliferation of vascular
      smooth muscle cells. Recently, a novel cyclooxygenase (COX)-2 pathway was shown
      to contribute to the anti-proliferative action of human apoE3 in vascular smooth
      muscle cells (VSMC). Here, we provide insight into the structure-function
      properties by which apoE mediates these effects. ApoE3 is most effective in
      promoting COX-2 expression as a lipid-free protein and is less active after
      lipidation. Alterations in the stability of the helix bundle N-terminal domain of
      apoE that contains the binding site for the low density lipoprotein (LDL)
      receptor and heparin do not affect the up-regulation of the COX-2 pathway. In
      addition, the apoE2, 3, and 4 isoforms are all capable of up-regulating the COX-2
      pathway. Finally, the effect of apoE on COX-2 was found to be independent of
      expression on the VSMC surface of the LDL receptor and heparan sulfate
      proteoglycans (HSPG). In summary, our data indicates that apoE, particularly in
      the lipid-free state, can up-regulate COX-2 in murine vascular smooth muscle
      cells apparently independently of binding to the LDLR, LRP or HSPG.

PMID- 17531998
TI  - Endothelial and leukocyte adhesion molecules in primary hypertriglyceridemia.
AB  - Hypertriglyceridemia is known to be associated to functional impairment of the
      endothelium and, consequently, to higher risk of atherosclerosis. Nevertheless,
      some crucial steps in the development of the atherosclerotic plaque are still
      unknown in primary hypertriglyceridemia. The aim of the present study was to
      explore the expression of soluble and leukocyte-associated cell adhesion
      molecules in a group of patients with primary hypertriglyceridemia, both
      including (n=50) and excluding (n=24) subjects with metabolic syndrome, in
      comparison with control normotriglyceridemic individuals (n=30). Lipid profile,
      CETP activity, HDL and VLDL chemical composition were evaluated. Soluble (VCAM-1,
      ICAM-1 and E-selectin) and leukocyte cell adhesion molecules (CD18, CD49d and
      CD54) were measured by enzyme-linked immunosorbent assay and flow cytometry,
      respectively. Patients with primary hypertriglyceridemia as compared with control
      subjects showed significantly higher VCAM-1 (15.6+/-4.5 ng/ml versus 13.9+/-3.8
      ng/ml, respectively; p<0.05) and ICAM-1 (16.9+/-3.1 ng/ml versus 15.2+/-3.2
      ng/ml, respectively; p<0.05). Regarding leukocyte cell adhesion molecules,
      significant increases were also detected in monocyte CD18 (398+/-180 versus 332+/
      136 arbitrary units, respectively; p<0.05) and CD54 (49+/-14 versus 42+/-12
      arbitrary units, respectively; p<0.05), and lymphocyte CD18 (122+/-53 versus
      101+/-33 arbitrary units, respectively; p<0.05). ICAM-1 plasma levels, as well as
      monocyte CD18 and CD54, and lymphocyte CD18 persisted elevated even if patients
      with metabolic syndrome were discarded among those with hypertriglyceridemia. The
      increase in circulating and leukocyte cell adhesion molecules in primary
      hypertriglyceridemic patients would highlight the inflammatory process which is a
      key event in atherogenesis.

PMID- 17531999
TI  - Dewetting phenomenon: interfacial water structure at well-organized alkanethiol
      modified gold-aqueous interface.
AB  - The interfacial properties at well-ordered short-chain alkanethiol monolayer
      aqueous interfaces are probed to understand the water structure near a
      hydrophobic surface. Monolayers of hexanethiol on highly oriented gold substrates
      have been prepared by various methods such as adsorption from alcoholic solution
      of the thiol, adsorption from neat thiol, and potential-controlled adsorption.
      The compactness and crystallinity of the monolayer have been probed using
      reflection-absorption infrared spectroscopy (RAIRS), atomic force microscopy
      (AFM), quartz crystal microbalance (QCM), and electrochemical techniques. The
      presence of a thin layer of solvent with reduced density/dielectric constant
      (termed "drying transition") close to the methyl groups is identified. This is
      based on reduced interfacial capacitance observed in the presence of an aqueous
      electrolyte solution as compared to the expected value for a well-ordered
      monolayer-aqueous interface. Atomic force microscopy allows the determination of
      the variation in the dielectric constant of the solvent medium as a function of
      distance from the monolayer head group. The thickness of the transition layer
      (interphase) is found to be approximately 2 nm. The phenomenon of drying
      transition is not unique to water; preliminary studies indicate that formamide,
      which has a two-dimensional hydrogen-bonded network, shows similar
      characteristics.

PMID- 17532000
TI  - Size-tuneable and micro-patterned iron nanoparticles derived from biomolecules
      via microcontact printing SAM-modified substrates and controlled-potential
      electrolyses.
AB  - Site-selected and size-controlled iron nanoparticles were prepared on coplanar
      surfaces via microcontact printing of SAM-modified Au/mica electrodes and
      controlled-potential electrolytic reactions using ferritin biomolecules. Ferritin
      molecules packed like a full monolayer on 6-amino-1-hexanethiol (AHT)- and 11
      amino-1-undecanethiol (AUT)-modified Au/mica surface via electrostatic
      interactions, which did not depend on the chain length of the amino terminal
      alkane thiols. After heat-treatment at 400 degrees C for 60 min, iron oxide
      nanoparticles (ca. 5 nm in diameter) derived from ferritin cores were observed at
      the Au/mica surface by atomic force microscopy (AFM). On the study on the
      electrochemistry of ferritin immobilized onto AHT- and AUT-modified Au/mica
      electrodes, the redox response of the ferritin immobilized AHT-modified electrode
      was clearly observed. On the other hand, no redox peak for ferritin was obtained
      at the AUT-modified electrode. The electron transfer between ferritin and the
      electrode through the AUT membrane could not take place. The difference in the
      electrochemical response of ferritin immobilized onto AHT- and AUT-modified
      Au/mica was caused by the chain length of the amino terminal alkane thiols.
      Uniform patterns of AHT and AUT on the Au/mica electrode surface were performed
      by use of a poly(dimethylsiloxane) (PDMS) stamp. After the immobilization of
      ferritin onto both AHT- and AUT-modified electrode surfaces, the modified
      electrode was applied to a -0.5 V potential for 30 min in a phosphate buffer
      solution. After this procedure, the PDMS stamp patterning image appeared by
      scanning electron microscopy (SEM) image. The SEM results induced by the size
      change of the ferritin core consisting of iron(III) by electrolysis.

PMID- 17532001
TI  - High throughput ranking of recombinant avian scFv antibody fragments from crude
      lysates using the Biacore A100.
AB  - Advances in molecular evolution strategies have made it possible to identify
      antibodies with exquisite specificities and also to fine-tune their biophysical
      properties for practically any specified application. Depending on the desired
      function, antibody/antigen interactions can be long-lived or short-lived and,
      therefore, particular attention is needed when seeking to identify antibodies
      with specific reaction-rate and affinity properties. Surface plasmon resonance
      (SPR) biosensors routinely generate sensitive and reliable kinetic data from
      antibody/antigen interactions for both therapeutic and diagnostic applications.
      However, many kinetic-based screening assays require rigorous sample preparation
      and purification prior to analysis. To ameliorate this problem, we developed a
      rapid and reliable assay for characterising recombinant scFv antibody fragments,
      directly from crude bacterial lysates. Ninety-six scFv antibodies derived from
      chickens immunised with C-reactive protein (CRP) were selected by phage display
      and evaluated using the Biacore A100 protein interaction array system. Antibodies
      were captured from crude bacterial extracts on the sensor chip surface and ranked
      based on the percentage of the complex left (% left) after dissociation in
      buffer. Kinetic rate constants (k(a) and k(d)) and affinity (K(D)) data were
      obtained for six clones that bound monomeric CRP across a broad affinity range
      (2.54 x 10(-8) to 3.53 x 10(-10) M). Using this assay format the A100 biosensor
      yielded high quality kinetic data, permitting the screening of nearly 400
      antibody clones per day.

PMID- 17532002
TI  - Meeting the energetic demands of insect diapause: nutrient storage and
      utilization.
AB  - Insects in diapause characteristically feed very little or not at all, thus they
      are largely or totally dependent on energy reserves sequestered prior to the
      entry into diapause. Fats are the dominant reserve used during this period, but
      non-fat reserves are also important for some species, especially during certain
      phases of diapause. Metabolic depression, coupled with the low temperatures of
      winter, facilitates the economic utilization of reserves during the many months
      typical of most diapauses. Though many insects store additional lipid prior to
      the entry into diapause, our review of the literature indicates that this is not
      always the case. We provide evidence that interactions between nutrient storage
      and metabolism can influence the decision to enter diapause and determine how
      long to remain in diapause. In addition, the energy reserves expended during
      diapause have a profound effect on post-diapause fitness. Though the
      physiological and biochemical mechanisms that regulate nutrient homeostasis prior
      to and during diapause remain poorly known, we propose several mechanisms that
      have the potential to contribute to diapause-associated nutrient homeostasis.
      Potential players include insulin signaling, neuropeptide F, cGMP-kinase, AMP
      activated protein kinase, and adipokinetic hormone.

PMID- 17532003
TI  - Interactions between isolates of the entomopathogenic fungus Metarhizium
      anisopliae and the entomopathogenic nematode Heterorhabditis bacteriophora JPM4
      during infection of the sugar cane borer Diatraea saccharalis (Lepidoptera:
      Pyralidae).
AB  - Interactions between the nematode Heterorhabditis bacteriophora isolate JPM4 and
      the fungus Metarhizium anisopliae, isolates LPP45 and LPP39, were studied during
      dual infections of Diatraea saccharalis. Mortality, production of infective
      juveniles (IJs) and production of conidia were evaluated. A positive effect was
      demonstrated for host mortality in duel infections of JPM4 and LPP39, causing
      100% mortality with LT(50) and LT(95) values of 1.8 and 2.8 days, respectively.
      Higher values were seen when using the nematode or fungi individually. However, a
      combination of JPM4+LPP39 caused a significant reduction in IJ production. The
      results show that faster time to death, a moderately virulent fungal isolate
      could be combined with the nematode, however at the expense of IJ production.

PMID- 17532004
TI  - Adiponectin and its receptors are expressed in adult ventricular cardiomyocytes
      and upregulated by activation of peroxisome proliferator-activated receptor
      gamma.
AB  - Adiponectin is a protein hormone involved in maintaining energy homeostasis in
      metabolically active tissues. It enhances glucose and lipid metabolism via
      activation of AMP-dependent kinase (AMPK) in skeletal muscle and liver. Energy
      homeostasis is vital for the heart to work as a pump. In this study, we
      investigated whether adiponectin and its receptors are expressed in adult
      ventricular cardiomyocytes. We observed adiponectin transcript and protein in
      cultured ventricular cardiomyocytes isolated from adult rat, by quantitative real
      time PCR, ELISA assays, Western blots, and immunofluorescent staining. In
      addition, we detected adiponectin receptor (AdipoR1 and AdipoR2) expression in
      the heart. AdipoR1 was expressed in rat myocardium at a level of approximately
      50% of that in skeletal muscle; whereas adipoR2 was expressed at a similar level
      to that in liver. Rosiglitazone, a Peroxisome proliferator activated receptor
      gamma (PPARgamma) activator, substantially elevated expression of adiponectin in
      cultured cardiomyocytes and its secretion into cultured media. Rosiglitazone also
      increased adipoR1 and adipoR2 expression in cardiomyocytes. Treatment of
      recombinant globular adiponectin in cultured cardiomyocytes increased fatty acid
      oxidation and glucose uptake via activation of AMPK, suggesting a role for
      adiponectin in cardiac energy metabolism. Together, these data establish the
      existence of a local cardiac-specific adiponectin system that is regulated by
      PPARgamma. Moreover, these findings indicate a role for adiponectin on normal
      myocardial energy homeostasis, in part, through the activation of AMPK.

PMID- 17532005
TI  - Mutations in capsid major homology region affect assembly and membrane affinity
      of HIV-1 Gag.
AB  - We introduced mutations into the HIV-1 major homology region (MHR; capsids 153
      172) and adjacent C-terminal region to analyze their effects on virus-like
      particle (VLP) assembly, membrane affinity, and the multimerization of the Gag
      structural protein. Results indicate that alanine substitutions at K158, F168 or
      E175 significantly diminished VLP production. All assembly-defective Gag mutants
      had markedly reduced membrane-binding capacities, but results from a velocity
      sedimentation analysis suggest that most of the membrane-bound Gag proteins were
      present, primarily in a higher-order multimerized form. The membrane-binding
      capacity of the K158A, F168A, and E175A Gag proteins increased sharply upon
      removal of the MA globular domain. While demonstrating improved multimerization
      capability, the two MA-deleted versions of F168A and E175A did not show marked
      improvement in VLP production, presumably due to a defect in association with the
      raft-like membrane domain. However, K158A bound to detergent-resistant raft-like
      membrane; this was accompanied by noticeably improved VLP production following MA
      removal. Our results suggest that the HIV-1 MHR and adjacent downstream region
      facilitate multimerization and tight Gag packing. Enhanced Gag multimerization
      may help expose the membrane-binding domain and thus improve Gag membrane
      binding, thereby promoting Gag multimerization into higher-order assembly
      products.

PMID- 17532006
TI  - Crystal structure of an asymmetric complex of pyruvate dehydrogenase kinase 3
      with lipoyl domain 2 and its biological implications.
AB  - A homodimer of pyruvate dehydrogenase kinase (PDHK) is an integral part of
      pyruvate dehydrogenase complex (PDC) to which it is anchored primarily through
      the inner lipoyl-bearing domains (L2) of transacetylase component. The catalytic
      cycle of PDHK and its translocation over the PDC surface is thought to be
      mediated by the "symmetric" and "asymmetric" modes, in which the PDHK dimer binds
      to two and one L2-domain(s), respectively. Whereas the structure of the symmetric
      PDHK/L2 complex was reported, the structural organization and functional role of
      the asymmetric complex remain obscure. Here, we report the crystal structure of
      the asymmetric PDHK3/L2 complex that reveals several functionally important
      features absent from the previous structures. First, the PDHK3 subunits have
      distinct conformations: one subunit exhibits "open" and the other "closed"
      configuration of the putative substrate-binding cleft. Second, access to the
      closed cleft is additionally restricted by local unwinding of the adjacent alpha
      helix. Modeling indicates that the target peptide might gain access to the PDHK
      active center through the open but not through the closed cleft. Third, the ATP
      binding loop in one PDHK3 subunit adopts an open conformation, implying that the
      nucleotide loading into the active site is mediated by the inactive "pre
      insertion" binding mode. Altogether our data suggest that the asymmetric complex
      represents a physiological state in which binding of a single L2-domain activates
      one of the PDHK protomers while inactivating another. Thus, the L2-domains likely
      act not only as the structural anchors but also modulate the catalytic cycle of
      PDHK.

PMID- 17532007
TI  - Analogs of SR-141716A (Rimonabant) alter d-amphetamine-evoked [3H] dopamine
      overflow from preloaded striatal slices and amphetamine-induced hyperactivity.
AB  - The CB(1) cannabinoid receptor antagonist SR-141716A (Rimonabant) markedly
      diminishes the behavioral effects of opiates and nicotine and has been an
      important tool to ascertain the role of cannabinoid receptors in drug addiction.
      The present goal was to determine the less-explored interaction of SR-141716A and
      d-amphetamine in neurochemical and behavioral assays. Additionally, the effect of
      the substituents and substitution patterns on the phenyl ring located at the 5
      position of SR-141716A (4-chlorophenyl), and of the CB(1)/CB(2) cannabinoid
      receptor agonist WIN-55,212-2, was determined. SR-141716A, AM-251 (4-iodophenyl)
      and NIDA-41020 (4-methoxyphenyl) did not alter amphetamine-evoked [(3)H]overflow
      from rat striatal slices preloaded with [(3)H]dopamine. MRI-8273-30-1 (4
      fluorophenyl; 0.1-10 microM) attenuated amphetamine (3 microM)-evoked
      [(3)H]overflow, and MRI-8273-59 (3,4-dichlorphenyl; 0.01-10 microM) augmented
      amphetamine (0.3-3 microM)-evoked [(3)H]overflow. WIN-55,212-2 was without
      effect. In a locomotor activity experiment, SR-141716A and MRI-8273-30-1 did not
      alter amphetamine-induced hyperactivity. However, MRI-8273-59 (1-3 mg/kg) dose
      dependently attenuated amphetamine (1 mg/kg)-induced hyperactivity. The present
      results suggest that SR-141716A is less efficacious to alter amphetamine effects
      than its reported efficacy to diminish the effects of opiates and nicotine.
      Modification of the 5-phenyl position of SR-141716A affords compounds that do
      interact with amphetamine in vitro and in vivo.

PMID- 17532008
TI  - Effect of asymmetric dimethylarginine on atherogenesis and erythrocyte
      deformability in apolipoprotein E deficient mice.
AB  - Previous investigations have shown that the level of asymmetric dimethylarginine
      (ADMA) was increased in hypercholesterolemic animal and humans, and the decreased
      erythrocyte deformability has been suggested to be a factor contributing to
      atherogenesis. In the present study, we investigated the effect of ADMA,
      endogenous or exogenous, on atherogenesis and erythrocyte deformability in
      apolipoprotein E deficient (ApoE-/-) mice. On a regular chow diet, ApoE-/- mice
      or C57BL/6 J mice at 12 weeks of age were treated with ADMA (5 mg/kg/day) for 4
      weeks. Atherosclerotic lesion area, erythrocyte deformability, plasma lipids and
      asymmetric dimethylarginine (ADMA) level were determined. Plasma concentrations
      of triglyceride (TG), low-density lipoprotein-cholesterol (LDL-C), total
      cholesterol (TC), ADMA, and atherosclerotic lesion area were significantly
      increased, and the level of plasma high-density lipoprotein-cholesterol (HDL-C),
      erythrocyte deformability in ApoE-/- mice were markedly decreased compared with
      that of C57BL/6J mice (P<0.05 or P<0.01). Exogenous ADMA treatment increased the
      plasma TG level, produced atherosclerotic lesions, and decreased erythrocyte
      deformability in C57BL/6J mice (P<0.05 or P<0.01). Treatment with exogenous ADMA
      further increased the plasma TG level and lesion areas, and decreased erythrocyte
      deformability in ApoE-/- mice. In vitro, exogenous ADMA caused a decrease of
      erythrocyte deformability in a concentration-dependent manner, and the effect of
      ADMA was reversed by L-arginine. The present results suggest that endogenous ADMA
      is an important contributor to the development of atherosclerosis and that
      reduction of erythrocyte deformability and impaired endothelial function induced
      by ADMA may be an important factor facilitating atherosclerotic lesions.

PMID- 17532009
TI  - Antioxidant properties of Krebs cycle intermediates against malonate pro-oxidant
      activity in vitro: a comparative study using the colorimetric method and HPLC
      analysis to determine malondialdehyde in rat brain homogenates.
AB  - A variety of Krebs cycle intermediaries has been shown to possess antioxidant
      properties in different in vivo and in vitro systems. Here we examined whether
      citrate, succinate, malate, oxaloacetate, fumarate and alpha-ketoglutarate could
      modulate malonate-induced thiobarbituric acid-reactive species (TBARS) production
      in rat brain homogenate. The mechanisms involved in their antioxidant activity
      were also determined using two analytical methods: 1) a popular
      spectrophotometric method (Ohkawa, H., Ohishi, N., Yagi, K., 1979. Assay for
      lipid peroxides in animal tissues by thiobarbituric acid reaction. Analytical
      Biochemistry 95, 351-358.) and a high performance liquid chromatographic (HPLC)
      procedure (Grotto, D., Santa Maria, L. D., Boeira, S., Valentini, J., Charao, M.
      F., Moro, A. M., Nascimento, P. C., Pomblum, V. J., Garcia, S. C., 2006. Rapid
      quantification of malondialdehyde in plasma by high performance liquid
      chromatography-visible detection. Journal of Pharmaceutical and Biomedical
      Analysis 43, 619-624.). Citrate, malate, and oxaloacetate reduced both basal and
      malonate-induced TBARS production. Their effects were not changed by pre
      treatment of rat brain homogenates at 100 degrees C for 10 min. alpha
      Ketoglutarate increased basal TBARS without changing malonate-induced TBARS
      production in fresh and heat-treated homogenates. Succinate reduced basal-
      without altering malonate-induced TBARS production. Its antioxidant activity was
      abolished by KCN or heat treatment. Fumarate reduced malonate-induced TBARS
      production in fresh homogenates; however, its effect was completely abolished by
      heat treatment. There were minimal differences among the studied methods.
      Citrate, oxaloacetate, malate, alpha-ketoglutarate and malonate showed iron
      chelating activity. We suggest that antioxidant properties of citrate, malate and
      oxaloacetate were due to their ability to cancel iron redox activity by forming
      inactive complexes, whereas alpha-ketoglutarate and malonate pro-oxidant activity
      can be due to formation of active complexes with iron. In contrast, succinate and
      fumarate antioxidant activity was probably due to some enzymatic system.

PMID- 17532011
TI  - Implication of stringent response in the increase of mutability of the whiG and
      whiH genes during Streptomyces coelicolor development.
AB  - In Streptomyces ambofaciens, genetic instability occurring during aerial mycelium
      development gives rise to white mutant papillae on colonies. Pig-pap mutants
      deriving from such papillae are unable to sporulate and devoid of the large
      genome rearrangement usually observed in the other Streptomyces mutants that
      genetic instability generated. Pig-pap mutants frequently harboured discrete
      mutations affecting the whiG gene. Furthermore, it has been established that the
      production of papillae dramatically increased when S. ambofaciens was grown under
      an amino acid limitation. In this work, we tested the implication of the
      stringent response, induced during an amino acid limitation, in the production of
      white papillae in Streptomyces coelicolor, a species which is phylogenetically
      close to S. ambofaciens. First, we showed that S. coelicolor produced mutant
      papillae and that this production was increased under an amino acid limitation.
      Secondly, we showed that the Pig-pap mutants generated both with and without
      amino acid limitation frequently exhibited mutations in whiH or whiG genes.
      Finally, we observed that a relA mutant of S. coelicolor, which was unable to
      elicit the stringent response under an amino acid limitation, was also unable to
      produce papillae. The restoration of the ability to elicit the stringent response
      also restored the papillae production. These papillae gave rise to Pig-pap
      mutants displaying the same characteristics as Pig-pap mutants spontaneously
      appearing on wild-type colonies. Altogether, these results show that whatever the
      underlying mechanism, the stringent response is involved in the production of
      white papillae in S. coelicolor.

PMID- 17532012
TI  - In search of autobiographical memories: A PET study in the frontal variant of
      frontotemporal dementia.
AB  - Patients suffering from frontal variant of frontotemporal dementia (fv-FTD)
      undergo autobiographical amnesia encompassing all time periods. We previously
      demonstrated in a group of 20 fv-FTD patients that this impairment involved
      deficits in executive function and semantic memory for all periods as well as new
      episodic learning and behavioural changes for the most recent period covering the
      last 12 months [Matuszewski, V., Piolino, P., de la Sayette, V., Lalevee, C.,
      Pelerin, A., Dupuy, B., et al. (2006). Retrieval mechanisms for autobiographical
      memories: Insights from the frontal variant of frontotemporal dementia,
      Neuropsychologia, 44, 2386-2397]. The aim of the present study was to unravel the
      neural bases of this impairment by mapping in a subgroup of patients correlations
      between resting-state brain glucose utilization measured by FDG-PET and measures
      of autobiographical memory (AM) using the TEMPau task which is designed to gauge
      personal event recollection across five life time periods. Like in our previous
      report, the group of patients was impaired regardless of time periods compared to
      healthy subjects providing generic memories instead of event specific sensory
      perceptual-affective details, i.e., episodic memories. New data showed that the
      patients were also impaired in sense of reliving and self-perspective during
      retrieval. The cognitivo-metabolic correlations between the AM score and resting
      normalized FDG-Uptake were computed using statistical parametric mapping (SPM2)
      and controlling for age and dementia severity. They revealed that AM deficits
      were mainly subserved by the dysfunction of left-sided orbitofrontal and also
      temporal neocortical areas whatever the period. Additional analysis showed that
      specific memories were associated with left orbitofrontal areas whereas generic
      memories were mainly associated with the left temporal pole. This study supports
      the view that fv-FTD patients undergo a breakdown of generative processes which
      relies regardless of the remoteness on the left orbitofrontal cortex and temporal
      neocortex to gain access to AM.

PMID- 17532010
TI  - Roles for VEGF in the adult.
AB  - The role of VEGF during development and in pathology is well known, but its
      function in normal adult tissues is poorly understood. Adverse effects associated
      with the use of anti-angiogenic therapies targeting VEGF in human pathologies
      have begun to reveal potential functions of VEGF in quiescent vasculature.
      Further clues from expression studies of VEGF and its receptors in the adult,
      from the disease preeclampsia, and from experimental neutralization studies, have
      suggested that VEGF is involved in endothelial cell survival and fenestration, as
      well as in the signaling and maintenance of non-endothelial cells. The various
      biochemical properties of VEGF, and its interaction with other growth factors,
      may be an important point in determining whether VEGF functions as a maintenance
      factor versus an angiogenic factor. A thorough understanding of the function of
      VEGF in the adult may lead to more efficacious pro- and anti-angiogenic
      therapies.

PMID- 17532013
TI  - Retronasal smell and detection thresholds of iron and copper salts.
AB  - Iron and copper salts, when placed in the mouth, may give rise to odorous
      compounds which complicate their functioning as chemical stimuli. The
      contribution of retronasal smell to perception of these metal salts at threshold
      has not been determined. Detection thresholds of the sulfate and chloride salts
      of ferrous iron and copper, and sodium chloride (as a control) were determined
      using a modified forced-choice ascending method of limits, with and without nasal
      occlusion. Threshold values were calculated from geometric means of individual
      estimates, and from interpolation on logistic regression and percent correct
      plots. Nasal occlusion raised thresholds for iron salts and copper but not
      sodium. The geometric mean detection thresholds with the nose open were 30, 64,
      7.8, and 8.2 microM for FeSO(4), FeCl(2), CuSO(4), CuCl(2), respectively but rose
      to 160, 227, 24.6 and 15.6 with the nose closed. Metal salts of both iron and
      copper create a retronasally perceived olfactory stimulus at low concentration
      levels, probably arising from lipid oxidation products generated in the mouth.

PMID- 17532014
TI  - Cannabinoid-induced hyperphagia: correlation with inhibition of
      proopiomelanocortin neurons?
AB  - We tested the hypothesis that cannabinoids modulate feeding in male guinea pigs,
      and correlated cannabinoid-induced changes in feeding behavior with alterations
      in glutamatergic synaptic currents impinging upon proopiomelanocortin (POMC)
      neurons of the hypothalamic arcuate nucleus. Feeding experiments were performed
      as follows: after a three-day acclimation period, animals were weighed and
      injected with either the CB1 receptor agonist WIN 55,212-2 (1 mg/kg, s.c.),
      antagonist AM251 (3 mg/kg, s.c.) or their cremophore/ethanol/saline vehicle
      (1:1:18; 1 ml/kg, s.c.) each day for seven days. WIN 55,212-2 increased, whereas
      AM251 decreased, the rate of cumulative food intake. The agonist effect was
      manifest primarily by increases in meal frequency and the amount of food eaten
      per meal. By contrast, the antagonist effect was associated with decreases in
      meal frequency, duration and weight loss. For the electrophysiological
      experiments, we performed whole-cell patch-clamp recordings from POMC neurons in
      hypothalamic slices. WIN 55,212-2 decreased the amplitude of evoked,
      glutamatergic excitatory postsynaptic currents (eEPSCs) and increased the S2:S1
      ratio. Conversely, AM251 increased eEPSC amplitude per se, and blocked the
      inhibitory effects of the agonist. WIN 55,212-2 also decreased miniature EPSC
      (mEPSC) frequency; whereas AM251 increased mEPSC frequency per se, and again
      blocked the inhibitory effect of the agonist. A subpopulation of cells exhibited
      an agonist-induced outward current, which was blocked by AM251, associated with
      increased conductance and reversed polarity near the Nernst equilibrium potential
      for K(+). These data demonstrate that cannabinoids regulate appetite in the
      guinea pig in part through both presynaptic and postsynaptic actions on
      anorexigenic POMC neurons.

PMID- 17532015
TI  - Flux quantification in central carbon metabolism of Catharanthus roseus hairy
      roots by 13C labeling and comprehensive bondomer balancing.
AB  - Methods for accurate and efficient quantification of metabolic fluxes are
      desirable in plant metabolic engineering and systems biology. Toward this
      objective, we introduce the application of "bondomers", a computationally
      efficient and intuitively appealing alternative to the commonly used isotopomer
      concept, to flux evaluation in plants, by using Catharanthus roseus hairy roots
      as a model system. We cultured the hairy roots on (5% w/w U-(13)C, 95% w/w
      naturally abundant) sucrose, and acquired two-dimensional [(13)C, (1)H] and
      [(1)H, (1)H] NMR spectra of hydrolyzed aqueous extract from the hairy roots.
      Analysis of these spectra yielded a data set of 116 bondomers of beta-glucans and
      proteinogenic amino acids from the hairy roots. Fluxes were evaluated from the
      bondomer data by using comprehensive bondomer balancing. We identified most
      fluxes in a three-compartmental model of central carbon metabolism with good
      precision. We observed parallel pentose phosphate pathways in the cytosol and the
      plastid with significantly different fluxes. The anaplerotic fluxes between
      phosphoenolpyruvate and oxaloacetate in the cytosol and between malate and
      pyruvate in the mitochondrion were relatively high (60.1+/-2.5 mol per 100 mol
      sucrose uptake, or 22.5+/-0.5 mol per 100 mol mitochondrial pyruvate
      dehydrogenase flux). The development of a comprehensive flux analysis tool for
      this plant hairy root system is expected to be valuable in assessing the
      metabolic impact of genetic or environmental changes, and this methodology can be
      extended to other plant systems.

PMID- 17532016
TI  - Compartment-specific labeling information in 13C metabolic flux analysis of
      plants.
AB  - Metabolic engineering of plants has great potential for the low cost production
      of chemical feedstocks and novel compounds, but to take full advantage of this
      potential a better understanding of plant central carbon metabolism is needed.
      Flux studies define the cellular phenotype of living systems and can facilitate
      rational metabolic engineering. However the measurements usually made in these
      analyses are often not sufficient to reliably determine many fluxes that are
      distributed between different subcellular compartments of eukaryotic cells. We
      have begun to address this shortcoming by increasing the number and quality of
      measurements that provide (13)C labeling information from specific compartments
      within the plant cell. The analysis of fatty acid groups, cell wall components,
      protein glycans, and starch, using both gas chromatography/mass spectrometry and
      nuclear magnetic resonance spectroscopy are presented here. Fatty acid labeling
      determinations are sometimes highly convoluted. Derivatization to butyl amides
      reduces the errors in isotopomer resolution and quantification, resulting in
      better determination of fluxes into seed lipid reserves, including both plastidic
      and cytosolic reactions. While cell walls can account for a third or more of
      biomass in many seeds, no quantitative cell wall labeling measurements have been
      reported for plant flux analysis. Hydrolyzing cell wall and derivatizing sugars
      to the alditol acetates, provides novel labeling information and thereby can
      improve identification of flux through upper glycolytic intermediates of the
      cytosol. These strategies improve the quantification of key carbon fluxes in the
      compartmentalized flux network of plant cells.

PMID- 17532017
TI  - Towards dynamic metabolic network measurements by multi-dimensional NMR-based
      fluxomics.
AB  - Novel technologies for measuring biological systems and methods for visualizing
      data have led to a revolution in the life sciences. Nuclear magnetic resonance
      (NMR) techniques can provide information on metabolite structure and metabolic
      dynamics at the atomic level. We have been developing a new method for measuring
      the dynamic metabolic network of crude extracts that combines [(13)C(6)]glucose
      stable isotope labeling of Arabidopsis thaliana and multi-dimensional
      heteronuclear NMR analysis, whereas most conventional metabolic flux analyses
      examine proteinogenic amino acids that are specifically labeled with partially
      labeled substrates such as [2-(13)C(1)]glucose or 10% [(13)C(6)]glucose. To show
      the validity of our method, we investigated how to obtain information about
      biochemical reactions, C-C bond formation, and the cleavage of the main
      metabolites, such as free amino acids, in crude extracts based on the analysis of
      the (13)C-(13)C coupling pattern in 2D-NMR spectra. For example, the combination
      of different extraction solvents allows one to distinguish complicated (13)C
      (13)C fine couplings at the C2 position of amino acids. As another approach, f1
      f3 projection of the HCACO spectrum also helps in the analysis of (13)C-(13)C
      connectivities. Using these new methods, we present an example that involves
      monitoring the incorporation profile of [(13)C(6)]glucose into A. thaliana and
      its metabolic dynamics, which change in a time-dependent manner with atmospheric
      (12)CO(2) assimilation.

PMID- 17532018
TI  - Growth inhibitory indole acetic acid polyacetylenic ester from Japanese ivy
      (Hedera rhombea Bean).
AB  - Polyacetylenes 1 and 2 were isolated from extracts of Japanese ivy (Hedera
      rhombea Bean) flower buds, with their chemical structures established on the
      basis of extensive 1D and 2D NMR and MS analyses. The absolute configurations of
      compounds 1 and 2 were determined by both chemical means, and by using the
      modified Mosher's method. Compound 1 is the first polyacetylene having an ester
      linkage between falcarindiol (3) and indole-3-acetic acid (IAA) moieties and 2
      also had an unique substructure containing a conjugated diene adjacent to a
      hydroxy group. Polyacetylenes 1, 2, and 3 were also subjected to assessment of
      growth inhibition against the shoot and root growth of the monocotyledon plants,
      rice and perennial ryegrass, as well as the dicotyledons, cockscomb, lettuce,
      cress, and fenugreek. The most bioactive compound appeared to be compound 1,
      while 2 showed no activity. Compound 1 selectively showed growth inhibitory
      activity against dicotyledons.

PMID- 17532019
TI  - Synthesis and antimicrobial evaluation of water-soluble, dendritic derivatives of
      epimeric 5alpha-cholestan-3-amines and 5alpha-cholestan-3-yl aminoethanoates.
AB  - To examine the effect of negatively charged steroidal amphiphiles on
      antimicrobial activity, two pairs of epimeric, dendritic tricarboxylato
      amphiphiles--4-(2-carboxyethyl)-4-[3-(5alpha-cholestan-3-yl)ureido]heptanedioic
      acid (1) and 4-(2-carboxyethyl)-4-[3-(5alpha-cholestan-3
      yloxycarbonylmethyl)ureido]heptanedioic acid (2)--were synthesized. A broad
      antimicrobial screen of 11 microbes revealed that these amphiphiles only showed
      good activity against a methicillin-resistant isolate of Staphylococcus aureus
      (MRSA) and modest activity against an unrelated strain of S. aureus. The best
      activity, a minimal inhibitory concentration (MIC) of 27 microM, was found for
      the 3beta epimer of 1 against MRSA.

PMID- 17532020
TI  - The nonstructural protein 8 (nsp8) of the SARS coronavirus interacts with its
      ORF6 accessory protein.
AB  - Severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) caused a severe
      outbreak in several regions of the world in 2003. The SARS-CoV genome is
      predicted to contain 14 functional open reading frames (ORFs). The first ORF (1a
      and 1b) encodes a large polyprotein that is cleaved into nonstructural proteins
      (nsp). The other ORFs encode for four structural proteins (spike, membrane,
      nucleocapsid and envelope) as well as eight SARS-CoV-specific accessory proteins
      (3a, 3b, 6, 7a, 7b, 8a, 8b and 9b). In this report we have cloned the predicted
      nsp8 gene and the ORF6 gene of the SARS-CoV and studied their abilities to
      interact with each other. We expressed the two proteins as fusion proteins in the
      yeast two-hybrid system to demonstrate protein-protein interactions and tested
      the same using a yeast genetic cross. Further the strength of the interaction was
      measured by challenging growth of the positive interaction clones on increasing
      gradients of 2-amino trizole. The interaction was then verified by expressing
      both proteins separately in-vitro in a coupled-transcription translation system
      and by coimmunoprecipitation in mammalian cells. Finally, colocalization
      experiments were performed in SARS-CoV infected Vero E6 mammalian cells to
      confirm the nsp8-ORF6 interaction. To the best of our knowledge, this is the
      first report of the interaction between a SARS-CoV accessory protein and nsp8 and
      our findings suggest that ORF6 protein may play a role in virus replication.

PMID- 17532021
TI  - A conserved binding site within the Tomato golden mosaic virus AL-1629 promoter
      is necessary for expression of viral genes important for pathogenesis.
AB  - We have identified a nine base pair sequence in Tomato golden mosaic virus that
      is required for binding of nuclear proteins from tobacco and Arabidopsis to viral
      DNA. The sequence is located within the promoter for a 0.7 kb complementary sense
      mRNA (AL-1629). Mutation of the binding site results in a two- to six-fold
      reduction in the accumulation of AL-1629 mRNA, leading to reduced AL2 and AL3
      gene expression. Viral sequences located immediately adjacent to the core binding
      site appear to influence AL2 and AL3 expression, but retain some binding affinity
      to a soluble host protein(s). The ability of a nuclear protein(s) to bind
      sequences within the AL-1629 promoter correlates with efficient viral DNA
      replication, as mutation of these sequences results in reduced viral DNA levels.
      Analysis of begomo- and curtoviruses indicates extensive conservation of this
      binding site, which suggests a common mechanism regulating expression of two
      viral genes involved in replication and suppression of host defense responses.

PMID- 17532022
TI  - Leaded electronic waste is a possible source material for lead-contaminated
      jewelry.
AB  - Highly leaded jewelry, often imported from China, remains widely available in the
      United States. Leaded electronic waste is exported from the United States to
      several Asian countries where solder is recovered and circuit boards are stripped
      of parts in small workshops. To assess whether electronic waste is being recycled
      into the jewelry, lead, tin and copper content of highly leaded jewelry samples
      were determined by atomic absorption spectrometry. Sixteen jewelry items
      previously determined to contain 20-80% lead by weight were analyzed. Samples
      were digested in nitric acid for analysis of lead and copper, and in aqua regia
      for analysis of tin. Six samples contained significant amounts of tin, from 20.8%
      to 29.9% by weight. In addition, copper was a significant minor component of five
      of these samples (up to 4% by weight). Copper (present at 10-40% by weight in
      circuit boards) was shown to rapidly move into heated lead-tin solder. The
      combined lead-tin-copper content of these six items ranges from 93.5% to 100%,
      suggestive of a solder-based source material. These results are consistent with
      the hypothesis that recycled circuit board solders are being used to produce some
      of the heavily leaded imported jewelry sold in the United States. Should this
      hypothesis be substantiated, it suggests that environmental policies to protect
      children's health must address both proper recycling of source materials as well
      as restrictions of the lead content in consumer goods.

PMID- 17532023
TI  - Stable isotope determination in wild and farmed gilthead sea bream (Sparus
      aurata) tissues from the western Mediterranean.
AB  - Stable isotopes of carbon and nitrogen (delta(13)C and delta(15)N) have been
      determined in wild and farmed gilthead sea bream (Sparus aurata) samples of white
      and red muscle, liver, gills and gonads. First, delta(13)C and delta(15)N values
      were determined in samples with and without lipid removal to check the possible
      effect of lipid content on the stable isotope values of the different tissues
      studied. Differences were found for delta(13)C in all tissues studied apart from
      white muscle of wild fish, the tissue with the lowest lipid content. For
      delta(15)N values no differences were found in wild fish tissues. Liver from
      farmed fish showed lower delta(15)N value after lipid removing. Further
      conclusions were based on results obtained from lipid-free samples. delta(13)C of
      cultured fish tissues showed a mean depletion of 2.9+/-0.4 per thousand compared
      to wild specimens, suggesting different sources of carbon in the diet, probably
      due to the feed used during sea-cage culture. Cultured gilthead sea bream tissues
      were significantly more enriched in nitrogen than wild specimens by an average of
      1.5+/-0.2 per thousand in white muscle, indicating a slight increase in the
      trophic level. Determination of stable isotope signatures of gilthead sea bream
      tissues allows clear discrimination between wild and cultured sea bream, and
      characterisation of differences in diet and feeding conditions in any tissue
      studied.

PMID- 17532024
TI  - Cu sorption on Phragmites australis leaf and stem litter: a kinetic study.
AB  - Decaying organic matter plays an important role in the cycling of metals in
      wetland ecosystems. Sorption kinetics of Cu(II) on Phragmites australis leaf and
      stem litter were studied. Fresh leaf and stem litter was sampled from a surface
      flow wetland at the end of the growing season. The effect of decomposition stage
      was studied with litter that had been decomposing for a period of 5 months. The
      Lagergren pseudo-first-order model, the pseudo-second-order model, the Elovich
      equation and two diffusion models based on spherical intra-particle diffusion
      were fitted to the experimental data. The sorption capacity was significantly
      affected by the decomposition of the litter. The sorption process was best
      described by the pseudo-second-order kinetics (R(2) approximately 0.99) but the
      rate constant was strongly dependent on the initial Cu concentration. The intra
      particle diffusion model fitted the data only slightly less (R(2)>0.95) than the
      pseudo-second-order model. A theoretical comparison revealed that the good fit
      with the pseudo-second-order kinetics could be indicative of intra-particle
      diffusion. Sorption kinetics observed for the leaf and stem litter at different
      metal concentrations showed a fast initial sorption followed by a slow sorption
      phase.

PMID- 17532025
TI  - Seasonal and time variability of heavy metal content and of its chemical forms in
      sewage sludges from different wastewater treatment plants.
AB  - Sewage sludges obtained from seven wastewater treatment plants from the province
      of Salamanca, Spain, were periodically sampled to determine seasonal and time
      variation of their elemental composition over 2000 to 2002. The aim of this paper
      was to provide additional insight to evaluate the potential environmental impact
      following soil incorporation of these materials as amendments. Aqua regia
      extractable metals (pseudo total content) of Cd, Cr, Cu, Ni, Pb and Zn were
      determined and furthermore, the main chemical forms of metals within the sludge
      were evaluated using a five-step fractionation procedure. All the studied sludges
      displayed high fertility properties due to their richness of OC, P and K. Total
      mean concentrations of Cd, Cr, Cu, Ni, Pb and Zn in the sludges were within the
      regulation of the Spanish legislation. Using an multifactor analysis of variance,
      significant differences between Cr, Cu, Ni, Pb and Zn pseudo total contents
      (p<0.01) of sludges at different sites were found while the Cd content was
      statistically similar. Also significant differences were found between these
      pseudo total contents of heavy metals in samples collected along the time after
      three years (0.001<p<0.08) and in samples taken at different seasonal periods
      (summer and winter) for Cr, Cu, Ni and Zn (0.001<p<0.07). The fractionated metals
      Cd, Ni and Zn were observed to be in mobile or bioavailable fraction of the
      sludge up to 35% of total metal content. Cu and Pb distributed in the organically
      bound fraction up to 25% and 60%, respectively. The Cd, Cr, Cu, Ni, Zn in sludges
      were predominantly bound within the oxide or silicate components. Significant
      differences between distribution fractions of metals considered together
      (p<0.001) were found at different years, and for each individual metal,
      significant differences can be observed between distribution fractions of sludges
      collected at different sites, times and seasonal periods. The results showed that
      the studied sludges can potentially enhance soil agronomic properties. The
      fractionation data indicated that most metals occur in weakly mobile, non
      bioavailable form, and only Cd, could have potential moderate mobility in soil
      water system.

PMID- 17532026
TI  - Arsenic in Oregon community water systems: demography matters.
AB  - Recently, the maximum contaminate level (MCL) for arsenic was lowered to 10
      microg/L in community water systems (CWS) throughout the United States. In this
      study, CWS in Oregon were assessed for the occurrence and magnitude of arsenic
      >10 microg/L between the effective and compliance dates for the new MCL. Ten CWS,
      with a combined population of 49,395, met the criteria for this study. Arsenic
      levels above the new MCL ranged from 11-25 microg/L. The demographic
      characteristics of these systems were queried and considered in the context of
      risk, exposure and outreach. A disproportionate percent of residents in affected
      CWS were of Hispanic origin (35%) compared to the statewide average (8%).
      Residents in these CWS had a lower median household income (20% less than the
      statewide average), a lower median age (32.5 vs. 36.3) and a higher percent of a
      second language spoken in the home besides English (34.6% vs. 12.1%) compared to
      the statewide census. These community characteristics have implications for
      exposure, risk and outreach associated with the occurrence of arsenic in drinking
      water. Consequently, demographic parameters are informative for risk management
      and communication and ultimately, beneficial to the affected public.

PMID- 17532027
TI  - Comparison of particle-phase polycyclic aromatic hydrocarbons and their
      variability causes in the ambient air in Ho Chi Minh City, Vietnam and in Osaka,
      Japan, during 2005-2006.
AB  - A comparative study of polycyclic aromatic hydrocarbons (PAHs) associated with
      particulate matter (TSP) in the ambient air in an urban area in Ho Chi Minh City,
      Vietnam and in Osaka, Japan was carried out from 2005 to 2006. The objective of
      this study was to investigate the environmental levels, emission sources,
      seasonal variations and health risk of eleven PAHs in the two cities, especially
      Ho Chi Minh City where air pollution is becoming a serious concern. The results
      showed that the concentrations of TSP and total PAHs were significantly higher in
      Ho Chi Minh City than levels in Osaka. The concentrations of 5- and 6-ring PAHs
      (BeP, BbF, BkF, BaP, BghiP and InP) were much higher in TSP samples in Ho Chi
      Minh City than in Osaka, accounting for 82% and 51% of total PAHs, respectively.
      These PAHs are known to be highly carcinogenic and mutagenic in humans. Vehicular
      emission is suggested as one of the main pollution sources of PAHs in both
      cities. Motorcycles and gasoline automobiles are suggested as the main emission
      sources of PAHs in Ho Chi Minh City, whereas diesel automobiles are the primary
      source in Osaka. Seasonal variations of PAHs were observed in this study; higher
      concentrations of PAHs were found in the rainy season (May-December) and lower
      concentrations corresponded to the dry season (February-April) in Ho Chi Minh
      City, while higher concentrations of PAHs were observed in the winter (November
      January) in Osaka. The number of sunshine hours was an important meteorological
      factor affecting seasonal variations of PAHs in Ho Chi Minh City, while the
      temperature was a main factor causing the variations of PAHs in Osaka. The high
      BaP equivalent concentration of 5- and 6-ring PAHs even in the ambient air is an
      alarming signal for harmfulness to human health and environmental quality in Ho
      Chi Minh City.

PMID- 17532028
TI  - Genital human papilloma virus infection in mentally-institutionalized virgins.
AB  - OBJECTIVE: Human papilloma virus (HPV) can cause cervical cancer. Risk factors
      for HPV infection are primarily related to sexual behavior. We determined the
      prevalence of HPV infection and abnormal cervical cytology in institutionalized
      women with no previous sexual experience. METHODS: The study subjects were 251
      patients who sought screening for cervical cancer (45.9+/-9.4 years, mean+/-S.D.,
      range, 14 to 66). They were institutionalized for psychosomatic disorders since
      childhood, and had no previous sexual experience. In addition to screening for
      cervical cancer, specimens for HPV testing were collected. RESULTS: No women who
      were positive for HPV DNA was detected, though 251 women without sexual
      experiences were screened by the hybrid capture 2 test including 26 types of HPV
      DNA. CONCLUSION: Transmission through means other than sexual intercourse may not
      exist because we could not detect HPV DNA in 251 women with no previous sexual
      experience.

PMID- 17532029
TI  - Primary retroperitoneal mucinous borderline tumor: a case report.
AB  - BACKGROUND: Primary retroperitoneal mucinous borderline tumors are rare. These
      tumors can be present in women with otherwise normal pelvic anatomy. CASE: A 22
      year-old woman with abdominal pain was found to have a large midline mass
      superior to the uterus with ascites. In surgery, a large mass was arising from
      the sigmoid mesentery. The pelvis was normal on inspection. Final pathology of
      the mass revealed borderline tumor (tumor of low malignant potential) and focus
      of ovarian tissue. CONCLUSION: This is a case report of primary retroperitoneal
      mucinous borderline tumor. The gynecologic oncologist should be aware of primary
      retroperitoneal tumors and the differential diagnosis.

PMID- 17532030
TI  - Urinary mesothelin provides greater sensitivity for early stage ovarian cancer
      than serum mesothelin, urinary hCG free beta subunit and urinary hCG beta core
      fragment.
AB  - OBJECTIVES: Early detection of ovarian cancer should improve overall survival.
      Multiple serum markers have been evaluated as possible tests to detect early
      stage disease, but few urine markers have been studied. Mesothelin has been
      detected in serum from patients with ovarian cancer, but has not been previously
      reported in urine. METHODS: Mesothelin was assayed in the serum and in the urine
      from 28 patients with early stage (I/II) invasive epithelial ovarian cancers, 111
      with advanced stage (III/IV) invasive disease and 19 with tumors of low malignant
      potential. Marker values have been compared to those in healthy controls and 115
      patients with benign pelvic masses. Thresholds were set to include 95% of
      mesothelin values for 127 sera and 89 urines from healthy women. Urine values
      were considered: (1) as assayed; (2) normalized using the ratio of serum to urine
      creatinine; and (3) normalized using the Cockroft-Gault formula for glomerular
      filtration rate (GFR). Urines were also assayed for human chorionic gonadotropin
      (hCG) free beta subunit and beta subunit core fragment and similarly normalized.
      RESULTS: Optimal sensitivity for early stage disease was obtained when urine
      mesothelin was normalized using GFR. A greater fraction of patients with early
      stage disease was detected with the mesothelin urine assay (42%) than with the
      serum assay (12%). Similarly, 75% of patients with advanced ovarian cancer had
      elevated mesothelin in urine compared to 48% in serum. Serum and urine levels of
      mesothelin correlated for early (p=0.02) and late (p<0.001) disease. Urine
      mesothelin exhibited greater sensitivity for early stage ovarian cancer than did
      hCG free beta subunit or beta subunit core fragment and complementarity was not
      observed. CONCLUSION: Urine mesothelin deserves further evaluation as a biomarker
      for detection of early stage ovarian cancer in combination with other urinary
      markers.

PMID- 17532031
TI  - Over-expression of hypoxia-inducible factor 1 alpha in ovarian clear cell
      carcinoma.
AB  - OBJECTIVE: Unlike other histological types of epithelial ovarian carcinoma,
      ovarian clear cell carcinoma is known to have very poor response to therapy even
      when discovered in its early stages. Since tumor hypoxia has been shown to be
      strongly associated with poor prognosis, deregulation of the representative
      factor of tissue hypoxia; hypoxia-inducible factor 1 alpha (HIF-1alpha) and
      related protein; Von Hippel-Lindau (VHL) may be associated with poor prognosis of
      ovarian clear cell carcinoma. METHODS: Immunolocalization of both HIF-1alpha and
      VHL was performed on 56 cases of paraffin-embedded tissue sections of four
      different histological types of epithelial ovarian carcinoma and 5 cases of
      benign ovarian tumors as a control. Quantitative RT-PCR analysis of both HIF1A
      and VHL was performed on RNA isolated from 61 microdissected frozen tissues of
      four different histological types of epithelial ovarian carcinoma and 6 cases of
      normal ovarian epithelial cells. Expression levels of HIF-1alpha and VHL in
      different histological types and correlation between HIF-1alpha and VHL were
      determined by nonparametric analysis by Kruskal-Wallis and Spearman's test.
      RESULTS: HIF-1alpha expression levels were significantly higher in ovarian clear
      cell carcinoma than in other histological types (P=0.001). We found no
      correlation between mRNA and protein expression level in any type of carcinoma
      specimens. Among endometrioid, serous, and mucinous carcinoma, there were no
      differences in HIF-1alpha expression (P=0.643). There was a negative correlation
      between HIF-1alpha and VHL in serous (r=-0.661, P=0.027) and in endometrioid
      carcinoma (r=-0.657 P=0.039), but no correlation was found between HIF-1alpha and
      VHL expression levels in ovarian clear cell carcinoma (P=0.60). CONCLUSIONS: The
      results suggest that the role of hypoxia may change according to the histological
      type of ovarian carcinoma. High expression of HIF-1alpha and its independence
      from VHL in ovarian clear cell carcinoma may confer chemoresistance in this
      histological type.

PMID- 17532032
TI  - Three-dimensional endometrial volume and 3-dimensional power Doppler analysis in
      predicting endometrial carcinoma and hyperplasia.
AB  - OBJECTIVE: To evaluate the accuracy of endometrial volume measurement and 3
      dimensional power Doppler analysis (3D-PDA) in the diagnosis of endometrial
      carcinoma and endometrial hyperplasia in women with post- and peri-menopausal
      bleeding. METHODS: 56 women with post-menopausal and 89 with peri-menopausal
      bleeding were enrolled. All were scheduled for hysteroscopy, dilatation and
      curettage, endometrial sampling or hysterectomy, and the ultrasound was performed
      within 24 h before the procedure. Endometrial thickness, endometrial volume,
      vascularity index (VI), flow index (FI) and vascularity flow index (VFI) were
      measured. These parameters were compared between the group of women with normal
      histology (including endometrial polyps) and the pathologic group (carcinoma and
      hyperplasia with or without atypia). RESULTS: Ninety women (62%) had normal
      histology, 26 (17.9%) had an endometrial polyp, 18 (12.5%) hyperplasia and 11
      (7.6%) had endometrial carcinoma. Mean endometrial thickness was 11 mm and 15.5
      mm in the normal and pathologic groups respectively (p<0.005). The mean
      endometrial volume was 6.87 cc and 15.5 cc in the two groups respectively
      (p<0.001). The VI was 2.27% and 2.95% in the two groups respectively (p=0.022).
      The FI was 18.6 and 23.6 in the two groups respectively (p=0.014). The VFI was
      0.68 and 0.89 in the two groups respectively (p=0.018). Using ROC the area under
      the curve was 0.698, 0.728, 0.621, 0.631, and 0.625 for endometrial thickness,
      endometrial volume, VI, FI and VFI respectively. The best predictor of
      endometrial carcinoma was an endometrial volume of 3.56 cc or more (sensitivity
      93.1%, specificity 36.2%). CONCLUSIONS: Endometrial volume and 3D-PDA are good
      diagnostic tools in predicting endometrial carcinoma and hyperplasia in women
      with post- and peri-menopausal bleeding.

PMID- 17532033
TI  - Relationship of estrogen and progesterone receptors to clinical outcome in
      metastatic endometrial carcinoma: a Gynecologic Oncology Group Study.
AB  - INTRODUCTION: The goal of this study was to explore the relationship between the
      expression of hormone receptors in metastatic endometrial tumors and clinical
      response to daily tamoxifen citrate and intermittent weekly medroxyprogesterone
      acetate. STUDY DESIGN: Patients with measurable recurrent or advanced endometrial
      cancer were enrolled on a clinical trial, Gynecologic Oncology Group Study 119. A
      pretreatment tumor biopsy was obtained and subjected to immunohistochemical
      analyses. Estrogen receptor-alpha (ER-alpha) and progesterone receptor (PR) were
      assessed on frozen tissues, and PR isoforms A and B were detected on fixed
      tissues. The receptors were scored using a semi-quantitative HSCORE, with a cut
      off greater than 75 considered positive. RESULTS: Of the 60 eligible patients, 45
      had evaluable tissues for all receptors. For ER, 40% of the cases were positive;
      for PR, 45% were positive. The sub-cellular distribution of PRA was exclusively
      nuclear, and 16% of the tumors demonstrated positive staining. PRB was nuclear
      and cytoplasmic, with 22% of the tumors staining for nuclear PRB and 36% of the
      tumors staining for cytoplasmic PRB. ER and PR from frozen tissues and PRA and
      cytoplasmic PRB from fixed tissues significantly decreased with increasing tumor
      grade. The co-expression of ER-alpha with PR from the frozen tissues (r=0.68,
      p<0.001) and PRA (r=0.58, p<0.001) from the fixed tissues was statistically
      significant. The ER HSCORE was related to both response and overall survival;
      there was no statistically significant correlation of PR with clinical response
      in this small number of patients. CONCLUSION: ER-alpha measured in metastatic
      endometrial carcinoma tissue prior to hormonal therapy was statistically
      significantly related to clinical response to daily tamoxifen and intermittent
      medroxyprogesterone acetate.

PMID- 17532034
TI  - Long-term methadone maintenance reduces protracted symptoms of heroin abstinence
      and cue-induced craving in Chinese heroin abusers.
AB  - BACKGROUND: Cession of heroin use may be followed by a protracted-abstinence (PA)
      syndrome consisting of craving, negative mood, and physiological changes. PA
      symptoms have rarely been compared between drug-free and methadone-maintained
      former heroin users after similar lengths of heroin abstinence. METHODS: Seventy
      former heroin users were included in one of four groups: in day 15-45 of
      methadone maintenance therapy (short-term MMT), in month 5-6 of MMT (long-term
      MMT), opiate-free for 15-45 days after methadone-assisted heroin detoxification
      (short-term post-methadone), and opiate-free for 5-6 months after methadone
      assisted heroin detoxification (long-term post-methadone). PA symptoms (negative
      mood, dyssomnia, somatization, and craving), and blood pressure and pulse were
      assessed pre- and post-neutral videotape and pre- and post-heroin videotape.
      RESULTS: Dyssomnia and the total PA score were worst in short-term post-methadone
      participants, mood was best in long-term MMT participants, and cue-induced
      craving was least severe in long-term MMT participants. Blood pressure and pulse
      did not differ across groups. CONCLUSIONS: Even after acute withdrawal, the first
      months of heroin abstinence after methadone-assisted detoxification may be more
      difficult in terms of cue-induced craving and other PA symptoms than the first
      months of heroin abstinence during MMT. Our findings add to the literature
      supporting MMT for prevention of cue-induced heroin craving.

PMID- 17532035
TI  - Not all proteins are created allergens.

PMID- 17532036
TI  - Socioeconomic inequalities in food purchasing: the contribution of respondent
      perceived and actual (objectively measured) price and availability of foods.
AB  - BACKGROUND: Research has shown that lower socioeconomic groups purchase foods
      that are less consistent with dietary recommendations. The price and availability
      of foods are thought to be important mediating factors between socioeconomic
      position and food purchasing. OBJECTIVES: We examined the relative contribution
      of the perceived and objectively measured price and availability of recommended
      foods to household income differences in food purchasing. METHODS: Using a face
      to-face interview, a random sample of Brisbane residents (n=812) were asked about
      their food purchasing choices in 2000. They were also asked about their
      perceptions of the price and availability of 'recommended' foods (i.e. choices
      lower in fat, saturated fat, sugar, salt or higher in fibre) in the supermarkets
      where they usually shopped. Audits measuring the actual availability and price of
      identical foods were conducted in the same supermarkets. RESULTS: Lower
      socioeconomic groups were less likely to make food purchasing choices consistent
      with dietary guideline recommendations. Objective availability and price
      differences were not associated with purchasing choices, nor did they contribute
      to socioeconomic inequalities in food purchasing choices. Perceived availability
      and price differences were associated with the purchase of recommended foods.
      Perceived availability made a small contribution to inequalities in food
      purchasing, however perceived price differences did not. CONCLUSION:
      Socioeconomic inequalities in food purchasing are not mediated by differential
      availability of recommended foods and differences in price between recommended
      and regular foods in supermarkets, or by perceptions of their relative price.
      However, differential perceptions of the availability of recommended foods may
      play a small role in food purchasing inequalities.

PMID- 17532037
TI  - Equine embryology: an inventory of unanswered questions.
AB  - Carl Hartman's title of 47 years ago is invoked in tribute to his first recovery
      of a bovine embryo 30 years before that, and his legacy of an emphasis on the
      value of descriptive and comparative studies in reproductive biology. The horse's
      qualification as a farm animal has waned since those times but, in a conference
      understandably dominated by research in ruminants and pigs, there are lessons to
      be learned from some peculiarities of equine embryonic development. Morphological
      and physiological features of the conceptus and its interaction with its
      environment during the first month of pregnancy are described and discussed, with
      emphasis on conceptus expansion, experimental study of the capsule and its
      associated proteins, and steroid production and metabolism by the various tissues
      within the conceptus. It is also suggested that easy access to entire conceptuses
      at advanced stages of development in horses offers valuable opportunities for
      comparative investigation of early organogenesis and fetal membrane
      differentiation and, possibly, how they are affected by embryo manipulation in
      vitro.

PMID- 17532038
TI  - The effect of in vitro treatment of bovine embryos with IGF-1 on subsequent
      development in utero to Day 14 of gestation.
AB  - Culture of bovine embryos with insulin-like growth factor-1 (IGF-1) can improve
      development to the blastocyst stage and embryo survival following transfer to
      heat-stressed, lactating dairy cows. Two experiments were conducted to determine
      whether IGF-1 could improve embryo survival and development at Day 14 after
      ovulation. In Experiment 1, non-lactating Holstein cows (n=58) were selected as
      recipients following synchronization for timed-embryo transfer. Embryos were
      produced in vitro and cultured with or without 100ng/mL IGF-1. At Day 7 after
      expected ovulation (Day 0), groups of 7-12 embryos were randomly transferred to
      each recipient. Embryos were recovered at Day 14. Embryo length and the presence
      or absence of an embryonic disc was recorded. Recovered embryos were cultured
      individually for 24h to determine interferon-tau (IFN-tau) secretion. There was
      no effect of IGF-1 on embryo recovery rate, embryo length or IFN-tau secretion.
      In Experiment 2, non-lactating (n=56) and lactating (n=35) Holstein cows were
      selected as recipients following synchronization for timed-embryo transfer.
      Embryos were produced as described in Experiment 1. At Day 7 after expected
      ovulation (Day 0), a single embryo was randomly transferred to each recipient.
      Embryos were recovered at Day 14. Embryo length and IFN-tau secretion were
      determined as in Experiment 1. Recovery rate at Day 14 tended (P=0.1) to be
      higher for recipients that received IGF-1 treated embryos compared to control
      embryos (43.2% versus 26.1%, respectively). There was no effect of IGF-1 on
      embryo length or IFN-tau secretion. In conclusion, results suggest that exposure
      to IGF-1 through Days 7-8 of development does not enhance capacity of embryos to
      prevent luteolysis. Results of the single embryo-transfer experiment suggested
      that IGF-1 treatment might affect embryo survival post-transfer as early as Day
      14 after ovulation. Further experimentation is warranted to verify this finding.

PMID- 17532039
TI  - The effect of 3-hydroxybutyrate and its derivatives on the growth of glial cells.
AB  - Sodium salts of D-3-hydroxybutyrate (D-3-HB), DL-3-hydroxybutyrate (DL-3-HB) and
      methyl (D)-3-hydroxybutyrate (M-3-HB), are derivatives of 3-hydroxybutyric acid
      (3-HB), a ketone body that is produced in vivo in animals including human. D-3-HB
      is the most common degradation product of microbial polyhydroxyalkanoates (PHA)
      that have been investigated for tissue engineering application. This study
      evaluated the in vitro effect of PHA degradation product 3-HB and its derivatives
      (collectively called 3-HB derivatives) on cell apoptosis and cytosolic Ca(2+)
      concentration of mouse glial cells. Results showed that the percentage of cells
      undergoing apoptosis decreased significantly in the presence of 3-HB and its
      derivatives as evidenced by flow cytometry. The in vitro study on cytosolic
      Ca(2+) concentration demonstrated that 3-HB derivatives dramatically elevated the
      cytosolic Ca(2+) concentration. Both the extracellular and intracellular Ca(2+)
      contributed as the sources of such Ca(2+) concentration elevation. The effect of
      3-HB derivatives on cytosolic Ca(2+) concentration could be reduced by
      nitredipine, an L-type voltage-dependent calcium channel antagonist. In
      comparison, M-3-HB worked more efficiently than D-3-HB and DL-3-HB did as M-3-HB
      is more efficient in permeation into the cells. All results indicated that 3-HB
      derivatives had an inhibitory effect on cell apoptosis which is mediated by
      signaling pathways related to the elevation of cytosolic Ca(2+) concentration.
      This positive effect helps explain the biocompatibility observed for PHA, it also
      points to the possibility of 3-HB derivatives regardless of chirality to become
      an effective neural protective agent.

PMID- 17532040
TI  - Upregulation of bone cell differentiation through immobilization within a
      synthetic extracellular matrix.
AB  - There is a need for new therapeutic strategies to treat bone defects caused by
      trauma, disease or tissue loss. Injectable systems for cell transplantation have
      the advantage of allowing the use of minimally invasive surgical procedures, and
      thus for less discomfort to patients. In the present study, it is hypothesized
      that Arg-Gly-Asp (RGD)-coupled in a binary (low and high molecular weight)
      injectable alginate composition is able to influence bone cell differentiation in
      a three-dimensional (3D) structure. Viability, metabolic activity, cytoskeleton
      organization, ultrastructure and differentiation (alkaline phosphatase (ALP), von
      Kossa, alizarin red stainings and osteocalcin quantification) of immobilized
      cells were assessed. Cells within RGD-modified alginate microspheres were able to
      establish more interactions with the synthetic extracellular matrix as visualized
      by confocal laser scanning microscope and transmission electron microscopy
      imaging, and presented a much higher level of differentiation (more intense ALP
      and mineralization stainings and higher levels of osteocalcin secretion) when
      compared to cells immobilized within unmodified alginate microspheres. These
      findings demonstrate that peptides covalently coupled to alginate were efficient
      in influencing cell behavior within this 3D system, and may provide adequate
      preparation of osteoblasts for cell transplantation.

PMID- 17532041
TI  - Homeobox gene HLX1 is a regulator of colony stimulating factor-1 dependent
      trophoblast cell proliferation.
AB  - The cytokine colony stimulating factor-1 (CSF-1) is a key regulator of the
      proliferation, differentiation and activation of mononuclear phagocytes. CSF-1
      also plays an important role in reproduction. CSF-1 is produced in the placenta
      and activates signal transduction pathways that significantly increase the
      proliferation of placental trophoblast cells in culture. The target genes
      activated by CSF-1 mediated signal transduction in the nucleus are not well
      understood. Here, we use placental trophoblast cells to investigate potential
      downstream effector genes of CSF-1. HLX1 is a homeobox gene that controls
      proliferation in embryonic cell types and haematopoietic cell lineages. We have
      shown HLX1 is expressed in placental trophoblast cells but its functional role in
      the placenta is unknown. Following CSF-1 stimulation, HLX1 mRNA expression was
      significantly increased in SGHPL-4 and HTR-8/SVNeo cultured trophoblast cells
      (p<0.001, n=3). siRNA-mediated reduction of HLX1 mRNA levels with four
      independent oligonucleotides (siRNAs) resulted in significantly decreased cell
      proliferation in both cell lines (p<0.001, n=4). When HLX1 mRNA levels were
      reduced in the presence of CSF-1 stimulation, proliferation remained
      significantly decreased (p<0.001, n=4) in both the cell lines. We have shown for
      the first time that a homeobox gene, HLX1, is a downstream effector gene of CSF
      1, that HLX1 regulates placental cell proliferation and that CSF-1 acts, at least
      in part, through HLX1 to control cell proliferation.

PMID- 17532042
TI  - T-type Ca2+ channel expression in human esophageal carcinomas: a functional role
      in proliferation.
AB  - In the present study the role of T-type Ca(2+) channels in cancer cell
      proliferation was examined. Seventeen human esophageal cancer cell lines were
      screened for T-type channels using RT-PCR and voltage-clamp recordings. mRNAs for
      all three T-type channel alpha(1)-subunits (alpha(1G), alpha(1H), and alpha(1I))
      were detected in all 17 cell lines: either alpha(1H) alone, alpha(1H) and
      alpha(1G), or all three T-type alpha(1)-subunits. Eleven cell lines were further
      subjected to voltage-clamp recordings: one, i.e. the TE8 cell line, was found to
      exhibit a typical T-type current while others exhibited a minimal or no T-type
      current. Cell proliferation assays were performed in the presence or absence of T
      type channel blocker mibefradil in KYSE150, KYSE180 and TE1 cells expressing mRNA
      for T-type channel alpha(1)-subunits but lacking T-type current, and TE8 cells
      exhibiting T-type current. Only TE8 cell proliferation was reduced by mibefradil.
      Silencing the alpha(1G)-gene that encodes functional T-type Ca(2+) channels in
      TE8 cells with type-specific shRNA transduction also significantly decreased TE8
      cell proliferation. The reduction of cell proliferation in TE8 cells was found to
      be associated with an up-regulation of p21(CIP1). Moreover, p53 silencing nearly
      abolished the up-regulation of p21(CIP1) resulting from mibefradil T-type channel
      blockade. Together, these findings suggest a functional role of T-type channels
      in certain esophageal carcinomas, and that inhibition of T-type channels reduces
      cell proliferation via a p53-dependent p21(CIP1) pathway.

PMID- 17532043
TI  - Characterization of the CD3zeta, CD3gammadelta and CD3epsilon subunits of the T
      cell receptor complex in Atlantic salmon.
AB  - The CD3 subunits are essential components of the T cell receptor complex,
      transmitting signals to the inside of the cell. We report here cDNAs and
      corresponding genes encoding CD3zeta, CD3gammadelta and CD3epsilon in Atlantic
      salmon, and real-time RT-PCR analysis to reveal their tissue-specific expression.
      Salmon CD3zeta is the subunit that shows the highest sequence similarity to the
      mammalian counterparts, comprising of a short extracellular (EX) part, a
      transmembrane (TM) peptide and a long cytoplasmic (CY) tail with three
      immunoreceptor tyrosine-based activation motifs (ITAMs). The gene encoding
      CD3zeta in salmon has 7 exons. Salmon CD3gammadelta (a forerunner of CD3gamma and
      CD3delta in mammals) and CD3epsilon are related molecules each having an Ig-like
      EX domain, a TM peptide and a CY tail with one ITAM. Two distinct CD3gammadelta
      genes were found, each having 6 exons. The gene encoding CD3epsilon in salmon has
      5 exons. RT-PCR also revealed a transcript from a degenerated CD3epsilon gene in
      salmon (Salmo salar) and brown trout (Salmo trutta). This pseudogene is located
      tail to tail to a CD3gammadelta gene in salmon and has a typical CD3epsilon gene
      structure with the exception of 1 extra exon. All the CD3 genes in salmon were
      most abundantly expressed in thymus but the expression of the CD3epsilon
      pseudogene was only a fraction of that from the intact CD3epsilon gene.

PMID- 17532045
TI  - Current status of coastal zone issues and management in China: a review.
AB  - This paper identifies and examines social-economic and environmental issues
      recently emerged in China's coastal zone. Evaluation of management scheme and
      progress in perspectives of coordinated legislation, institutional arrangement,
      public participation, capacity building, and scientific research (mainly coastal
      planning and functional zoning) in China's coastal zone are made. The Chinese
      government has made a significant effort in developing legislation for the
      coastal zone. Jurisdictional and zoning boundaries, and allocating use rights for
      coastal and marine resources have been established. State Oceanic Administration
      is the leading agency responsible for China's ocean policymaking and overall
      management of ocean and coastal affairs. A demonstrated project for integrated
      coastal management in Xiamen has been implemented, and is characterized as
      "decentralization" approach in decision-making process. In view of the above,
      comprehensive coastal management in China is a big challenge, facing with many
      difficulties. Finally, recommendations are raised for tackling these issues for
      China's coastal zone management.

PMID- 17532046
TI  - Initial diagnosis of leprosy in patients treated by an ophthalmologist and
      confirmation by conventional analysis and polymerase chain reaction.
AB  - PURPOSE: To report the initial diagnosis of leprosy in patients seeking treatment
      from an ophthalmologist in a tertiary eye care center, its confirmation by
      histopathologic and polymerase chain reaction analysis, and review of literature.
      DESIGN: Noncomparative retrospective case series. PARTICIPANTS: Patients with no
      known history of leprosy who were selected based on either a clinical suspicion
      or a histopathologic diagnosis and were found to have ocular or periocular
      lesions suggestive of leprosy. METHODS: Review of clinical records of patients
      with no known history of leprosy seen by an ophthalmologist at a tertiary eye
      care referral center. MAIN OUTCOME MEASURES: Patient demographics, presenting
      symptoms and signs, diagnostic studies, complications, and treatment. RESULTS:
      Among the 6 patients (5 women and 1 man; average age, 55 years), only 2 were
      found to have leprosy from clinical examination alone. Histopathologic
      characteristics or demonstration of acid-fast bacilli, suggestive of leprosy,
      were found in 5 patients. Definite confirmation of leprosy was made by polymerase
      chain reaction performed on formalin-fixed, paraffin-embedded tissues of 4
      patients having suspected leprosy based on clinicohistopathologic examination
      results. CONCLUSIONS: The diagnosis of leprosy relies on the clinical symptom
      complex, epidemiologic factors, and demonstration of acid-fast bacilli in the
      tissue sample. Considering that the global leprosy population is 12 million, a
      patient with leprosy may be found anywhere. The ophthalmologist may be the first
      one to encounter such patient, in which case suspicion and detection of ocular
      findings may lead to early treatment of the infection. Polymerase chain reaction
      may be a new tool in the definite diagnosis of leprosy when suspicion of the
      diseases is raised by clinicohistopathologic studies.

PMID- 17532044
TI  - The behavioral actions of lithium in rodent models: leads to develop novel
      therapeutics.
AB  - For nearly as long as lithium has been in clinical use for the treatment of
      bipolar disorder, depression, and other conditions, investigators have attempted
      to characterize its effects on behaviors in rodents. Lithium consistently
      decreases exploratory activity, rearing, aggression, and amphetamine-induced
      hyperlocomotion; and it increases the sensitivity to pilocarpine-induced
      seizures, decreases immobility time in the forced swim test, and attenuates
      reserpine-induced hypolocomotion. Lithium also predictably induces conditioned
      taste aversion and alterations in circadian rhythms. The modulation of
      stereotypy, sensitization, and reward behavior are less consistent actions of the
      drug. These behavioral models may be relevant to human symptoms and to clinical
      endophenotypes. It is likely that the actions of lithium in a subset of these
      animal models are related to the therapeutic efficacy, as well the side effects,
      of the drug. We conclude with a brief discussion of various molecular mechanisms
      by which these lithium-sensitive behaviors may be mediated, and comment on the
      ways in which rat and mouse models can be used more effectively in the future to
      address persistent questions about the therapeutically relevant molecular actions
      of lithium.

PMID- 17532047
TI  - Late-onset hyaloideocapsular block syndrome.
AB  - PURPOSE: To report an unusual cause of decreased vision in an aphakic patient.
      DESIGN: Interventional case report. PARTICIPANT: One patient. INTERVENTION: An 80
      year-old woman presented with a myopic shift and decreased visual acuity in the
      left eye 16 years after extracapsular cataract extraction (ECCE) without
      intraocular lens (IOL) implantation. Slit-lamp examination after pupil dilation
      revealed a milky fluid accumulation between the posterior lens capsule and the
      anterior hyaloid membrane. A neodymium:yttrium-aluminium-garnet (Nd:YAG) laser
      hyaloidotomy was performed on the anterior hyaloid membrane. MAIN OUTCOME
      MEASURES: Refraction and best-corrected visual acuity. RESULTS: The Nd:YAG laser
      hyaloidotomy allowed the trapped fluid to flow into the vitreous cavity. The
      myopic shift disappeared immediately and visual acuity improved. CONCLUSIONS: To
      our knowledge, this is the first report of a late-onset hyaloideocapsular block
      syndrome after ECCE without IOL implantation.

PMID- 17532048
TI  - The ocular surface of glaucoma patients treated over the long term expresses
      inflammatory markers related to both T-helper 1 and T-helper 2 pathways.
AB  - PURPOSE: To investigate the expression of CCR5 and CCR4, two chemokine receptors,
      as markers of the T helper (Th) 1 and Th2 pathways, respectively, and class II
      antigen HLA-DR as a hallmark of inflammation on conjunctival cells obtained from
      patients receiving long-term glaucoma treatment. DESIGN: Case-control study.
      PARTICIPANTS: A total of 18 normal subjects and 70 glaucoma patients treated with
      topical antiglaucoma drugs for more than 1 year: 14 receiving a beta-blocker as
      monotherapy, 38 treated with a prostaglandin analog alone (19 with latanoprost, 6
      with travoprost, 13 with bimatoprost), and 18 receiving multiple treatments.
      METHODS: Impression cytologic specimens (ICSs) were obtained from 1 eye of the
      patients and processed for flow cytometry. Conjunctival cells were extracted and
      incubated with monoclonal antibodies against CCR4, CCR5, HLA-DR, or their
      specific controls to measure, in a masked manner, the percentages of conjunctival
      cells positive for the 3 markers. MAIN OUTCOME MEASURES: HLA-DR and chemokine
      receptors (CCR4 and CCR5) in ICSs. RESULTS: Compared with all other groups, HLA
      DR expression was raised significantly in the multitreatment group, whereas all
      monotherapies showed slight and nonsignificant increases. Both CCR4 and CCR5 were
      increased significantly in all 5 glaucoma groups compared with normal subjects,
      with no between-group differences. CONCLUSIONS: This study demonstrates the
      overexpression of 2 chemokine receptors in the conjunctival epithelium of
      glaucoma patients treated over the long term. These results show the simultaneous
      overexpression of CCR4 and CCR5, suggesting that the chronic use of topical
      treatments may stimulate both the Th1 and Th2 systems simultaneously. These
      results also suggest that inflammatory mechanisms combining allergy with toxicity
      are at work and illustrate the complexity of inflammatory reactions occurring in
      the ocular surface of glaucoma patients.

PMID- 17532049
TI  - Specific interactions of metal ions with Cys-Xaa-Cys unit inserted into the
      peptide sequence.
AB  - In this work five peptides with Cys-Xaa-Cys motif were studied including Ac-Cys
      Gly-Cys-NH(2), Ac-Cys-Pro-Cys-Pro-NH(2), their N-unprotected analogues and the N
      terminal fragment of metallothionein-3, Met-Asp-Pro-Glu-Thr-Cys-Pro-Cys-Pro
      NH(2). All these peptides were found to be very effective ligands for Ni(2+),
      Zn(2+) and Cd(2+) ions. Potentiometric and spectroscopic (UV-Vis, CD and MCD)
      studies have proved that sulfur atoms are critical donors for the metal ions
      coordination. The amide nitrogen may participate in the metal ion binding only in
      the case when Gly is adjacent to Cys residues. Ac-Cys-Gly-Cys-NH(2) may serve as
      a low molecular weight model for cluster A, which is a binding unit of nickel ion
      in acetyl coenzyme A synthase. This bifunctional enzyme from anaerobic
      microorganisms catalyzes the formation of acetyl coenzyme A from CO, a methyl
      group donated by the corrinoid-iron-sulfur protein and coenzyme A. Other peptides
      studied in this work were Ac-Cys-Pro-Cys-Pro-NH(2) and Met-Asp-Pro-Glu-Thr-Cys
      Pro-Cys-NH(2) originating from metallothionein sequence. These motifs are
      characteristic for the sequence of cysteine rich metallothionein-3 (MT-3) called
      also neuronal growth inhibitory factor (GIF). Cys-Pro-Cys-Pro fragment of protein
      was demonstrated to be crucial for the inhibitory activity of the protein.

PMID- 17532050
TI  - A minimally invasive procedure for sexing young zebra finches.
AB  - Zebra finches have been widely used to study neurobiology underlying vocal
      development. Because only male zebra finches learn song, efficient developmental
      use of these animals requires early determination of sex at ages that precede
      maturation of secondary sex characteristics. We have developed a sex
      determination method that combines a forensics method of genomic DNA isolation
      (from very small blood samples) with PCR amplification from Z and W sex
      chromosomes (males are ZZ, females ZW). This combination results in a minimally
      invasive yet highly reliable and convenient genotyping method.

PMID- 17532051
TI  - The responsiveness of EQ-5D utility scores in patients with depression: A
      comparison with instruments measuring quality of life, psychopathology and social
      functioning.
AB  - INTRODUCTION: The EQ-5D provides preference weights (utilities) for health
      related quality of life to be used for calculating quality-adjusted life years
      (QALYs) in cost-utility analysis. The aim of this study was to compare
      differences in EQ-5D utility scores with differences in quality of life,
      psychopathology, and social functioning scores. METHODS: In an observational
      longitudinal cohort study, EQ-5D utilities (EQ visual analogue scale (EQ VAS), EQ
      5D indices of the United Kingdom (EQ-5D index-UK) and Germany (EQ-5D index-D))
      were compared with scores of the WHOQOL-BREF, CGI, and GAF at baseline and at 18
      months (N=104). The patients' health status at follow-up was categorized as
      "worse", "stable", or "better" using the EQ-5D transition question (patient-based
      anchor) and the Bech-Rafaelsen melancholy scale (clinician-based anchor). Effect
      sizes (ES) were used to compare differences in scores within each group over
      time; regression analysis was used to derive meaningful difference scores in
      health status associated with a shift from "stable" to "better" health status.
      RESULTS: The most responsive instrument was the CGI (patient-based anchor:
      ES=|0.98|; clinician-based anchor: ES=|1.35|); responsiveness was large in EQ VAS
      (patient-based anchor: ES=|0.84|; clinician-based anchor: ES=|1.19|), but rather
      small to medium for EQ-5D index-UK (patient-based anchor: ES=|0.55|; clinician
      based anchor: ES=|0.65|) and EQ-5D index-D (patient-based anchor: ES=|0.41|;
      clinician-based anchor: ES=|0.45|). Compared with the other instruments, the
      shift to a "better health status" was smaller if elicited by the EQ-5D indices.
      DISCUSSION: Both EQ-5D indices were less responsive and need larger patient
      samples to detect meaningful differences compared with EQ VAS and the other
      instruments.

PMID- 17532052
TI  - Depressive symptoms and antidepressant use in a random community sample of
      ethnically diverse, urban elder persons.
AB  - BACKGROUND: There are limited data on depressive symptoms and antidepressant use
      in ethnically diverse, urban elderly. METHODS: Analysis of depressive symptom and
      antidepressant use data from an epidemiological survey of dementia in an
      ethnically diverse, urban, elderly community. RESULTS: 21.5% (N=566) reported
      clinically significant depressive symptoms. Severity was inversely associated
      with socioeconomic status. 7.5% (N=194) reported antidepressant medication use.
      Multiple logistic regression analysis adjusting for severity and other covariates
      showed that men and African Americans had nearly half the odds of using
      antidepressants. Antidepressant use was more frequent among Hispanics, those with
      more severe depression and more medical illness. LIMITATIONS: Combined sample;
      CES-D not validated in Hispanics and inner-city African Americans; depressive
      symptoms assessed at one time-point; lack of complete income data; geographically
      restricted. CONCLUSIONS: In this elder sample, taking into account depressive
      symptom severity and other confounds, antidepressant use is nearly half as likely
      among men and African Americans.

PMID- 17532053
TI  - Bcl6 is required for the IL-4-mediated rescue of the B cells from apoptosis
      induced by IL-21.
AB  - IL-21 has a pro-apoptotic effect on freshly isolated B cells stimulated with LPS,
      and also induces Bcl6 expression in the activated B cells. However, a role for
      Bcl6 in the activated B cells is not known. When naive B cells from Bcl6
      deficient mice were stimulated with LPS plus IL-21, those B cells died by
      apoptosis as wild-type B cells. Co-stimulation of those B cells with IL-4
      partially rescued the wild-type B cells but not the Bcl6-deficient B cells from
      the IL-21-induced apoptosis. Bcl-2 was not up-regulated in both B cells
      stimulated with LPS plus IL-21 and IL-4. Bcl-X(L) and Bax were up-regulated in
      both B cells stimulated with LPS plus IL-4, and the co-stimulation with IL-21 did
      not modulate these up-regulations in wild-type B cells. However, the co
      stimulation clearly suppressed the Bcl-X(L) up-regulation but not the Bax up
      regulation in Bcl6-deficient B cells. Thus, Bcl6 is required for maintaining the
      Bcl-X(L) up-regulation in B cells stimulated with LPS plus IL-21 and IL-4, and
      the up-regulation may partially rescue the B cells from apoptosis induced by IL
      21.

PMID- 17532054
TI  - The effect of 17beta-estradiol on IL-6 secretion and NF-kappaB DNA-binding
      activity in human retinal pigment epithelial cells.
AB  - Toll-like receptors (TLRs) and inflammatory cascades participate in the pathology
      of age-related macular degeneration (AMD). The effect of estrogens on the
      development of AMD is poorly understood, although many studies indicate that
      these compounds can modulate inflammatory responses. In this study, we
      investigated the regulatory role of TLR agonists and 17beta-estradiol (E(2)) on
      IL-6 expression and NF-kappaB DNA-binding activity in human retinal pigment
      epithelial cells (ARPE-19). The inflammatory response of ARPE-19 cells to various
      TLR agonists, e.g. Pam, zymosan, flagellin, SLTA and lipopolysaccharide (LPS)
      exposures were examined via the secretion of IL-6 cytokine as analyzed by ELISA.
      In addition, the IL-6 responses to the estrogen-receptor agonist, E(2), and to
      the estrogen-receptor antagonist ICI 182.780 as well as to the NF-kappaB
      inhibitor helenalin were compared. The DNA-binding activity of NF-kappaB
      transcription factor of nuclear cell extracts was analyzed by the gel mobility
      shift assay (EMSA). TLR4 gene expression was studied by quantitave PCR. The TLR4
      agonist, LPS, caused a clear IL-6 response that was attenuated by E(2) in ARPE-19
      cells. The anti-inflammatory properties of E(2) were mediated through estrogen
      receptors and were associated with decreased NF-kappaB DNA-binding activity. The
      level of TLR4 gene expression was not affected by LPS exposure. Our results
      indicate that IL-6 expression is regulated through NF-kappaB transcription factor
      and stereoid-receptor signalling pathways in ARPE-19 cells.

PMID- 17532055
TI  - Mycoplasma contamination and viral immunomodulatory activity: dendritic cells
      open Pandora's box.
AB  - During in vitro investigations on the interaction of classical swine fever virus
      (CSFV)--an immunosuppressive viral pathogen--with monocyte-derived dendritic
      cells (MoDC) a soluble factor with a strong anti-proliferative activity for T
      lymphocytes was found. This activity, with an inhibitory dilution 50% (ID(50)) of
      10(3)-10(7), was induced after virus infection of monocytes differentiating into
      DC. UV--inactivation of the supernatants and blocking experiments with a
      monoclonal antibody against the E2 envelope protein of CSFV initially indicated a
      virus-dependency. However, further investigations including filtration and
      centrifugation experiments as well as antibiotic treatment demonstrated the
      involvement of mycoplasma. This was confirmed by a Hoechst 33258 staining, PCR
      and mycoplasma cultures--Mycoplasma hyorhinis was identified as the contaminant.
      Elucidation of a mycoplasma presence occurred under conditions in which the
      original virus stocks prepared in SK6 cells were negative for mycoplasma using
      the above tests. Moreover, conventional passage of the virus on the SK6 cells
      used for this purpose did not reveal any mycoplasma. It was the passage of virus
      in MoDC rather than SK6 cells that was required to expose the contamination.
      Three passages of the anti-proliferative supernatants on MoDC cultures increased
      the ID(50) 10(3)-fold; only when these MoDC-derived supernatants were employed
      was the mycoplasma contaminant also detectable on SK6 cells. In conclusion, these
      data demonstrate that regular testing of cell lines and virus stocks for
      mycoplasma does not necessarily identify their presence, and that application of
      passage in MoDC cultures could prove an aid for identifying initially
      undetectable levels of mycoplasma contamination.

PMID- 17532056
TI  - Exogenous VIP limits zymosan-induced generalized inflammation (ZIGI) in mice.
AB  - Vasoactive intestinal peptide (VIP) was administered in a model of zymosan
      induced generalized inflammation (ZIGI). Its beneficial action was associated
      with reduced TNF-alpha and increased IL-10 production, lowered levels of
      creatinine, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and
      bilirubin in circulation. VIP diminished the level of RANTES and MIP-1alpha in
      peritoneal exudate and circulation. The neuropeptide inhibited NO release from
      stimulated peritoneal macrophages. Decreased spleen, liver and kidney enlargement
      and less pathological changes in liver were observed. The effect of VIP was
      attenuated by pretreatment with VIP antagonist (anti-VIP) before the induction of
      shock.

PMID- 17532057
TI  - Thymosin-alpha1 modulates dendritic cell differentiation and functional
      maturation from human peripheral blood CD14+ monocytes.
AB  - Although thymosins have been demonstrated to have immunomodulatory effects, it is
      still not clear whether they could affect dendritic cells (DCs), the most
      professional antigen-presenting cells. The objective of this study was to
      determine the effect and potential mechanisms of thymosin-alpha1 (Talpha1) on DC
      differentiation and functional maturation. Human peripheral blood CD14(+)
      monocytes were purified by using a magnetic separation column and cultured with
      GM-CSF and IL-4 to differentiate into immature DCs (iDCs). In the presence of
      Talpha1, iDC surface markers CD40, CD80, MHC class I and class II molecules were
      significantly upregulated as measured by flow cytemotry analysis. However, Tbeta4
      or Tbeta10 did not show these effects on iDCs. There was an approximately 30%
      reduction in antigen (FITC-conjugated dextran)-uptake by Talpha1-treated iDCs as
      compared with non-Talpha1-treated iDCs. In addition, Talpha1-treated matured DCs
      (mDCs) showed an increased stimulation of allogeneic CD3(+) T-cell proliferation
      as measured by a mixed-lymphocyte reaction assay. Talpha1-treated mDCs also
      increased the production of several Th1- and Th2-type cytokines as measured by a
      Bio-Plex cytokine assay. Furthermore, rapid activation of p38 MAPK and NFkappaB
      was seen in Talpha1-treated iDCs as measured by a Bio-Plex phosphoprotein assay.
      Thus, Talpha1 significantly enhances DC differentiation, activation, and
      functions from human peripheral blood CD14(+) monocytes possibly through a
      mechanism of the activation of p38 MAPK and NFkappaB pathways. This study
      provides a basis to further evaluate Talpha1 as a possible adjuvant for a DC
      directed vaccine or therapy.

PMID- 17532058
TI  - T-cell Ig and mucin domain-containing protein (Tim)-2 regulates murine allergic
      conjunctivitis during the effector phase.
AB  - T-cell Ig and mucin domain-containing protein (Tim)-2 is associated with Th2
      dependent immune responses. Here, we investigated whether administration of anti
      Tim-2 Abs affects the development of murine experimental allergic conjunctivitis
      (EC), a Th2-mediated disease. While treatment with anti-Tim-2 Abs in vivo during
      the induction phase did not affect the severity of EC, treatment during the
      effector phase augmented EC. The in vitro stimulation of ragweed (RW)-primed
      splenocytes with RW in the presence of anti-Tim-2 Abs induced significantly more
      IL-5 and IL-13 production but significantly less IFN-gamma production compared
      with the control splenocytes treated with normal rat IgG. In addition, the
      transfer of the anti-Tim-2 Ab-treated splenocytes induced significantly more
      severe EC than the control splenocytes. Thus, Tim-2 negatively regulates the Th2
      differentiation of Ag-primed T-cells and the development of EC during the
      effector phase.

PMID- 17532059
TI  - Role of GABAergic inhibition in hippocampal network oscillations.
AB  - Physiological rhythmic activity in cortical circuits relies on GABAergic
      inhibition to balance excitation and control spike timing. With a focus on recent
      experimental progress in the hippocampus, here we review the mechanisms by which
      synaptic inhibition can control the precise timing of spike generation, by way of
      effects of GABAergic events on membrane conductance ('shunting' inhibition) and
      membrane potential ('hyperpolarizing' inhibition). Synaptic inhibition itself can
      be synchronized by way of interactions within networks of GABAergic neurons, and
      by excitatory neurons. The importance of GABAergic mechanisms for generation of
      cortical rhythms is now well established. What remains to be resolved is how such
      inhibitory control of spike timing can be harnessed for long-range fast
      synchronization, and the relevance of these mechanisms to network function. This
      review is part of the INMED/TINS special issue Physiogenic and pathogenic
      oscillations: the beauty and the beast, based on presentations at the annual
      INMED/TINS symposium (http://inmednet.com).

PMID- 17532060
TI  - Pathological synchronization in Parkinson's disease: networks, models and
      treatments.
AB  - Parkinson's disease is a common and disabling disorder of movement owing to
      dopaminergic denervation of the striatum. However, it is still unclear how this
      denervation perverts normal functioning to cause slowing of voluntary movements.
      Recent work using tissue slice preparations, animal models and in humans with
      Parkinson's disease has demonstrated abnormally synchronized oscillatory activity
      at multiple levels of the basal ganglia-cortical loop. This excessive
      synchronization correlates with motor deficit, and its suppression by
      dopaminergic therapies, ablative surgery or deep-brain stimulation might provide
      the basic mechanism whereby diverse therapeutic strategies ameliorate motor
      impairment in patients with Parkinson's disease. This review is part of the
      INMED/TINS special issue, Physiogenic and pathogenic oscillations: the beauty and
      the beast, based on presentations at the annual INMED/TINS symposium
      (http://inmednet.com/).

PMID- 17532061
TI  - Behavioural characterisation of the robotic mouse mutant.
AB  - The ataxic mouse mutant robotic is characterised by progressive adult-onset
      Purkinje cell loss that occurs in a distinctive region-specific pattern. We
      report the first behavioural characterisation of this mutant and quantify its
      performance on tests of motor function, locomotor and exploratory activity over a
      time course that reflects specific stages of cell loss in the cerebellum. Robotic
      mutants are significantly impaired on the rotarod and static rod tests of
      coordination and their performance declined during aging. In addition, gait
      analysis revealed an increase in the severity of the ataxia displayed by mutants
      over time. Interestingly, spontaneous alternation testing in a T-maze was not
      significantly affected in robotic mice, unlike other ataxic mutants with more
      rapid and extensive cerebellar degeneration; robotic therefore provides an
      opportunity to investigate the necessity of specific Purkinje cell populations
      for various behavioural tasks.

PMID- 17532062
TI  - Functional characterization of two missense mutations in Pex5p - C11S and N526K.
AB  - Most newly synthesized peroxisomal proteins are targeted to the organelle by
      Pex5p, the peroxisomal cycling receptor. Pex5p interacts with these proteins in
      the cytosol, transports them to the peroxisomal docking/translocation machinery
      and promotes their translocation across the organelle membrane. Finally, Pex5p is
      recycled back to the cytosol in order to catalyse additional rounds of
      transportation. Although several properties of this protein sorting pathway have
      been recently uncovered, we are still far from comprehending many of its basic
      principles. Here, we describe the mechanistic implications of two single-amino
      acid substitutions in Pex5p. The first mutation characterized, Cys11Ser, blocks
      the recycling of Pex5p back into the cytosol at the step in which stage 2 Pex5p
      is converted into stage 3 Pex5p. The mutation Asn526Lys, previously described in
      a child with neonatal adrenoleukodystrophy and shown to abolish the PTS1-binding
      capacity of Pex5p, results in a Pex5p protein exhibiting import capacity.
      Protease assays suggest that the Asn526Lys mutation causes conformational
      alterations at the N-terminal half of Pex5p mimicking the ones induced by binding
      of a PTS1-containing peptide to the normal peroxin. The implications of these
      findings on the mechanism of protein translocation across the peroxisomal
      membrane are discussed.

PMID- 17532063
TI  - Prostasin induces protease-dependent and independent molecular changes in the
      human prostate carcinoma cell line PC-3.
AB  - Expression of prostasin in the PC-3 human prostate carcinoma cells inhibited in
      vitro invasion, but the molecular mechanisms are unknown. Wild-type human
      prostasin or a serine active-site mutant prostasin was expressed in the PC-3
      cells. Molecular changes were measured at the mRNA and the protein levels. Cell
      signaling changes were evaluated by measuring phosphorylation of the
      extracellular signal-regulated kinases (Erk1/2) following epidermal growth factor
      (EGF) treatment of the cells. Protein expression of the EGF receptor (EGFR) was
      differentially down-regulated by the wild-type and the active-site mutant
      prostasin. The mRNA expression of EGFR and the transcription repressor SLUG was
      reduced in cells expressing wild-type prostasin but not the active-site mutant.
      Phosphorylation of Erk1/2 in response to EGF was greatly reduced by the wild-type
      prostasin but not by the active-site mutant. The mRNA expression of the urokinase
      type plasminogen activator (uPA), the uPA receptor (uPAR), cyclooxygenase-2 (COX
      2), and the inducible nitric oxide synthase (iNOS) was decreased by the wild-type
      and the active-site mutant prostasin. The mRNA or protein expression of
      granulocyte-macrophage colony-stimulating factor (GM-CSF), matriptase, and E
      cadherin was greatly increased by the active-site mutant prostasin. In
      conclusion, prostasin expression elicits both protease-dependent and independent
      molecular changes in the PC-3 cells.

PMID- 17532064
TI  - A propensity-matched study of the association of physical function and outcomes
      in geriatric heart failure.
AB  - Most heart failure (HF) patients are older adults. However, the association of
      functional status and outcomes in ambulatory older adults with chronic HF has not
      been well studied. Of the 7788 Digitalis Investigation Group (DIG) trial
      participants, 4036 were > or =65 years. Of these, 1369 (34%) had New York Heart
      Association (NYHA) class III-IV symptoms. We calculated propensity scores for
      NYHA III-IV symptoms for all 4036 patients using a non-parsimonious logistic
      regression model. We used propensity scores to match 1010 (74% of 1369) NYHA III
      IV patients with 1010 of NYHA I-II patients. Kaplan-Meier and matched Cox
      proportion hazard analyses were used to estimate associations of NYHA class III
      IV with mortality and hospitalizations. Patients had a mean age of 73 years, 31%
      were female, and 11% were nonwhites. All-cause mortality occurred in 394 (rate,
      1385/10000 person-years) NYHA I-II and 452 (rate, 1654/10000 person-years) NYHA
      III-IV patients, respectively, during 2967 and 2733 years of follow up (hazard
      ratio: {HR}, 1.28; 95% confidence interval {CI}, 1.09-1.50; p=0.002). NYHA III-IV
      class was associated with increased cardiovascular (HR, 1.25; 95% CI, 1.04-1.49;
      p=0.016) and HF mortality (HR, 1.51; 95% CI, 1.16-1.97; p=0.002). NYHA III-IV
      class was not significantly associated with hospitalizations due to all causes
      (HR, 1.10; 95% CI, 0.96-1.25; p=0.165), cardiovascular causes (HR, 1.11; 95% CI,
      0.96-1.29; p=0.150), or worsening HF (HR, 1.09, 95% CI, 0.92-1.30; p=0.330).
      Baseline NYHA functional class was associated with mortality but not with
      hospitalization in ambulatory older adults with chronic HF.

PMID- 17532065
TI  - Factors associated with sexuality in later life: An exploratory study in a group
      of Greek married older adults.
AB  - The present study aimed to investigate factors associated with sexual interest
      and behaviors in married older adults. The study recruited older adults from the
      Open Protection Centers for Elderly. A 30-items questionnaire addressing
      sexuality, emotional and physical intimacy, demographics, and background data was
      constructed. Dichotomous responses were used for intimacy and sexuality items.
      Data were analyzed using Chi-square tests, Pearson's correlation coefficient and
      Independent samples t-test. The sample consisted of 454 married participants (age
      range: 60-90, mean: 69.0+/-6.5). More than 50% reported having sexual desire and
      intercourse's average frequency of 4/month. Increasing age and marriage's years
      related significantly to decreased frequency of sexual intercourse (p<0.001).
      Participants married out of love reported higher frequency of intercourse p.a.
      compared with those in arranged marriages (p=0.031). Gender, age, income, married
      out of love and being still in love with the partner were all significantly
      associated with sexual interest and behaviors (p<0.05). This study demonstrates
      that older adults remain sexually active and a range of personal, socio-economic
      and interpersonal factors are associated with sexual interest. Therefore, sexual
      expression should be a well-informed individual's choice and not the result of
      societal myths or health professionals' misconceptions.

PMID- 17532066
TI  - Myocardial capillary supply is limited in hypertrophic cardiomyopathy: a
      morphological analysis.
AB  - OBJECTIVE: To clarify the morphological basis of the limited coronary reserve in
      hypertrophic cardiomyopathy (HCM). BACKGROUND: Some of the symptoms in
      Hypertrophic cardiomyopathy (HCM), such as chest pain, dyspnea and arrhythmia,
      may be explained by myocardial ischemia. Many patients with HCM are known to
      exhibit these symptoms in the absence of atherosclerosis in the major coronary
      vessels. Decreased myocardial perfusion has been demonstrated in HCM, however,
      little is known about the myocardial capillary morphology in this disease.
      METHODS: Using immunohistochemistry and morphometry, we analysed capillaries and
      cardiomyocytes in myectomy specimens from 5 patients with HCM with moderate
      hypertrophy and left ventricular outflow tract obstruction and in 5 control
      hearts. RESULTS: The number of capillaries per cardiomyocyte (p<0.009) and number
      of capillaries per cardiomyocyte area unit, reflecting cardiomyocyte mass
      (p=0.009), were lower in individuals with HCM, i.e. indicating loss of
      capillaries. In HCM, the capillary density was 33% lower (p<0.05). CONCLUSIONS:
      Our morphologic findings show that the capillary supply, and thus the coronary
      reserve, is impaired in HCM with moderate hypertrophy and left ventricular
      outflow tract obstruction. These data may partly explain the limitation of
      myocardial perfusion in HCM, which is associated with worse prognosis.
      Furthermore, we present evidence of actual loss of myocardial capillaries in HCM
      and a defective capillary growth.

PMID- 17532067
TI  - Heart rate adjustments and analysis of recovery patterns of ST-segment depression
      in type 2 diabetes.
AB  - AIMS: To investigate the diagnostic value for coronary artery disease (CAD)
      detection of evaluating time- and heart rate (HR)-related ST-segment changes (the
      ST/HR-slope) and the post-exercise recovery pattern (the ST/HR-recovery loop) in
      patients with type 2 diabetes mellitus (T2DM). METHODS AND RESULTS: Ninety-one
      patients (22 female, age 59+/-9 years) with T2DM (diabetes duration 6+/-6 years)
      performed an exercise ECG-test that was evaluated using the ST/HR slope (cut
      off</=-2.4 microV/bpm) and -recovery loop patterns (abnormal versus normal) and
      compared to the conventional >/=1 mm ST-segment depression criterion and
      dobutamine stress echo-cardiography, all evaluated against coronary angiography
      irrespective of stress test results. Coronary angiography revealed CAD in 20 men
      and 3 women (25%). Sensitivity for the conventional exercise test and stress
      echocardiography was low (0.35 and 0.30), but increased significantly using the
      ST/HR-slope (0.45), the recovery loop (0.86) or the combined ST/HR slope and
      recovery loop criterion (0.91). The associations between angiographic CAD
      detection and the different tests expressed by the Odds ratio demonstrated an
      added value of performing ST/HR analysis both over pre-test CAD risk profile and
      the established techniques. CONCLUSION: T2DM patients capable of performing an
      exercise test could be assessed with the ST/HR-analysis for selecting patients to
      angiography. However, further studies including a higher number of patients are
      needed to confirm the diagnostic value of this approach.

PMID- 17532068
TI  - Viral myocarditis masquerading acute coronary syndrome (ACS)--MRI to the rescue.
AB  - A young man with a strong family history of myocardial infarction with sudden
      death presented with chest pain and was found to have positive cardiac biomarkers
      and echocardiographic evidence of inferolateral wall hypokinesia. He was managed
      as an acute coronary syndrome and underwent a thorough ischemic work-up which was
      negative. Subsequently, a cardiac MRI was performed that demonstrated a patchy
      subepicardial enhancement, most consistent with acute viral myocarditis. This
      case demonstrates the importance of cardiac MRI in distinguishing an acute
      coronary syndrome from viral myocarditis.

PMID- 17532069
TI  - Prevalence and risk factors for Salmonella spp. and Campylobacter spp. caecal
      colonization in broiler chicken and turkey flocks slaughtered in Quebec, Canada.
AB  - We conducted an observational study to estimate prevalence and risk factors for
      Salmonella spp. and Campylobacter spp. caecal colonization in poultry. Eighty-one
      broiler chicken and 59 turkey flocks selected among flocks slaughtered in the
      province of Quebec, Canada, were included in the study. Flock status was
      evaluated by culturing pooled caecal contents from about 30 birds per flock.
      Exposure to potential risk factors was evaluated with a questionnaire. Odds
      ratios were computed using multivariable logistic regression. The prevalence of
      Salmonella-positive flocks was 50% (95% CI: 37, 64) for chickens and 54% (95% CI:
      39, 70) for turkeys, respectively. Odds of Salmonella colonization were 2.6 times
      greater for chicken flocks which failed to lock the chicken house permanently. In
      turkeys, odds of Salmonella colonization were 4.8-7.7 times greater for flocks
      which failed to be raised by <or=2 producers with no other visitors allowed onto
      the premises, or origin from a hatchery. The prevalence of Campylobacter-positive
      flocks was 35% (95% CI: 22, 49) for chickens and 46% (95% CI: 30, 62) for
      turkeys. Odds of colonization were 4.1 times higher for chicken flocks raised on
      farms with professional rodent control and 5.2 times higher for flocks with
      manure heap >200m from the poultry house, and also increased with the number of
      birds raised per year on the farm and with the age at slaughter. For turkeys,
      odds of Campylobacter flock colonization were 3.2 times greater in flocks having
      a manure heap at </=200m from poultry house and 4.2 times greater in flocks
      drinking unchlorinated water.

PMID- 17532070
TI  - Clustering of parasites within cages on Scottish and Norwegian salmon farms:
      alternative sampling strategies illustrated using simulation.
AB  - Within the literature, most discussion of sampling protocols for monitoring
      aquatic parasites is based on the assumptions of simple random sampling. Recent
      research has shown that in monitoring parasite abundance on fish farms composed
      of discrete cages, care must be taken to properly account for the clustering
      which naturally occurs. This paper illustrates the effect of clustering in the
      context of monitoring ectoparasitic sea lice Lepeophtheirus salmonis and Caligus
      elongatus in salmon farms. The degree of clustering of sea lice infections in
      fish within cages is measured using the intraclass correlation coefficient (ICC).
      A wide range of ICC values from sites in Scotland and Norway were estimated for
      the chalimus and mobile stages of L. salmonis, and for C. elongatus mobiles. The
      analyses indicate that significant clustering of lice infections within cages
      occurs across lice species and stages on both Scottish and Norwegian farms. A
      Monte-Carlo simulation using two sets of data from Scottish farms with ICC values
      for adult L. salmonis of 0.35 [0.08-0.73, 95% CI] and for adult C. elongatus of
      0.39 [0.16-0.69, 95% CI] were used to illustrate the implications of clustering.
      The protocols simulated reflect those typically used across a range of countries
      and production environments in which salmon are currently reared. The findings
      demonstrate that the "few fish from many cages" approach results in a marked
      improvement in precision when sampling aquatic one-host parasites in cage-based
      production systems.

PMID- 17532071
TI  - Microbial preparation of metal-substituted magnetite nanoparticles.
AB  - A microbial process that exploits the ability of iron-reducing microorganisms to
      produce copious amounts of extra-cellular metal (M)-substituted magnetite
      nanoparticles using akaganeite and dopants of dissolved form has previously been
      reported. The objectives of this study were to develop methods for producing M
      substituted magnetite nanoparticles with a high rate of metal substitution by
      biological processes and to identify factors affecting the production of nano
      crystals. The thermophilic and psychrotolerant iron-reducing bacteria had the
      ability to form M-substituted magnetite nano-crystals (M(y)Fe(3-y)O(4)) from a
      doped precursor, mixed-M iron oxyhydroxide, (M(x)Fe(1-x)OOH, x< or =0.5, M is Mn,
      Zn, Ni, Co and Cr). Within the range of 0.01< or =x< or =0.3, using the mixed
      precursor material enabled the microbial synthesis of more heavily substituted
      magnetite compared to the previous method, in which the precursor was pure
      akaganeite and the dopants were present as soluble metal salts. The mixed
      precursor method was especially advantageous in the case of toxic metals such as
      Cr and Ni. Also this new method increased the production rate and magnetic
      properties of the product, while improving crystallinity, size control and
      scalability.

PMID- 17532072
TI  - Development and application of a microtiter plate-based autoinduction bioassay
      for detection of the lantibiotic subtilin.
AB  - Production of the lantibiotic subtilin in Bacillus subtilis ATCC 6633 is
      regulated in a quorum sensing-like mechanism with subtilin acting as autoinducer
      and signal transduction via the subtilin-specific two-component regulation system
      SpaRK. Here, we report the construction and application of a subtilin reporter
      strain in which subtilin induced lacZ gene expression in a B. subtilis ATCC 6633
      spaS gene deletion mutant is monitored and visualized by the beta-galactosidase
      in a chromogenic plate assay. A quantitative microtiter plate subtilin bioassay
      was developed and optimized. Maximal sensitivity of the system was achieved after
      6 h of incubation of the reporter strain together with subtilin in a medium
      containing 300 mM NaCl. This sensitive and unsusceptible method was applied to
      identify subtilin producing B. subtilis wild type strains from both, culture
      collections and soil samples. The B. subtilis lantibiotic ericin S with four
      amino acid exchanges compared to subtilin induces the subtilin reporter strain,
      in contrast to the structurally closely related Lactococcus lactis lantibiotic
      nisin. These observations suggest a certain substrate specificity of the
      histidine kinase SpaK, which however, also would allow the identification of
      subtilin-isoform producing microorganisms.

PMID- 17532073
TI  - Concurrent celecoxib versus placebo in patients with stage II-III non-small cell
      lung cancer: a randomised phase II trial.
AB  - In several pre-clinical models, cyclooxygenase (COX) inhibitors increase radio
      sensitivity of tumours, whilst not affecting normal tissues. A randomised phase
      II trial comparing concurrent radiotherapy with either celecoxib or placebo in
      patients with stage II-III non-small cell lung cancer was therefore initiated.
      Because of poor recruitment, the study was stopped after the enrollment of 41
      patients, instead of the foreseen 102. None of the endpoints differed
      significantly between both groups. However, due to the limited number of
      patients, no definitive conclusions can be drawn.

PMID- 17532074
TI  - Impact of supervised gene signatures of early hypoxia on patient survival.
AB  - BACKGROUND AND PURPOSE: Hypoxia is a common feature of solid tumors associated
      with therapy resistance, increased malignancy and poor prognosis. Several
      approaches have been developed with the hope of identifying patients harboring
      hypoxic tumors including the use of microarray based gene signatures. However,
      studies to date have largely ignored the strong time dependency of hypoxia
      regulated gene expression. We hypothesized that use of time-dependent patterns of
      gene expression during hypoxia would enable development of superior prognostic
      expression signatures. MATERIALS AND METHODS: Using published data from the
      microarray study of Chi et al., we extracted gene signatures correlating with
      induction during either early or late hypoxic exposure. Gene signatures were
      derived from in vitro exposed human mammary epithelial cell line (HMEC) under 0%
      or 2% oxygen. Gene signatures correlating with early and late up-regulation were
      tested by means of Kaplan-Meier survival, univariate, and multivariate analysis
      on a patient data set with primary breast cancer treated conventionally (surgery
      plus on indication radiotherapy and systemic therapy). RESULTS: We found that the
      two early hypoxia gene signatures extracted from 0% and 2% hypoxia showed
      significant prognostic power (log-rank test: p=0.004 at 0%, p=0.034 at 2%) in
      contrast to the late hypoxia signatures. Both early gene signatures were linked
      to the insulin pathway. From the multivariate Cox-regression analysis, the early
      hypoxia signature (p=0.254) was found to be the 4th best prognostic factor after
      lymph node status (p=0.002), tumor size (p=0.016) and Elston grade (p=0.111). On
      this data set it indeed provided more information than ER status or p53 status.
      CONCLUSIONS: The hypoxic stress elicits a wide panel of temporal responses
      corresponding to different biological pathways. Early hypoxia signatures were
      shown to have a significant prognostic power. These data suggest that gene
      signatures identified from in vitro experiments could contribute to
      individualized medicine.

PMID- 17532075
TI  - Pupillary responses during lexical decisions vary with word frequency but not
      emotional valence.
AB  - Pupillary responses were examined during a lexical decision task (LDT). Word
      frequency (high and low frequency words) and emotional valence (positive, neutral
      and negative words) were varied as experimental factors incidental to the
      subjects. Both variables significantly affected lexical decision performance and
      an interaction effect was observed. The behavioral results suggest that
      manipulating word frequency may partly account for the heterogeneous literature
      findings regarding emotional valence effects in the LDT. In addition, a
      difference between high and low frequency words was observed in the pupil data as
      reflected by higher peak pupil dilations for low frequency words, whereas
      pupillary responses to emotionally valenced words did not differ. This result was
      further supported by means of a principal component analysis on the pupil data,
      in which a late component was shown only to be affected by word frequency.
      Consistent with previous findings, word frequency was found to affect the
      resource allocation towards processing of the letter string, while emotionally
      valenced words tend to facilitate processing.

PMID- 17532076
TI  - Damned if you do, damned if you don't: the differential effect of expression and
      inhibition of anger on cardiovascular recovery in black and white males.
AB  - Appropriate regulation of emotions is an important component of health. The
      physiological effects of coping with anger are a topic of particular interest. In
      a pioneering series of studies Hokanson found that the mode of anger expression
      following anger instigation had differential effects on vascular recovery. These
      differential effects were thought to be a result of social learning of avoidance
      responses. The present study examined this hypothesis in the context of ethnic
      differences in cardiovascular recovery responses to anger instigation. Twenty
      four African American (AA) and 26 European American (EA) males engaged in two
      debates, one racially themed and one non-racially themed, with an EA confederate.
      Cardiovascular measures were recorded at baseline, during the debates and during
      10-minute recovery periods following each debate. Anger expression preceding the
      recovery period was manipulated such that half the participants could express
      their anger toward the confederate and half had to inhibit their anger toward the
      confederate. Results showed that both AA and EA participants that inhibited their
      anger had delayed total peripheral resistance recovery. Importantly, for the
      other dependent variables differential recovery responses were observed such that
      EA participants that expressed their anger recovered more quickly whereas AA
      participants that expressed their anger recovered more slowly. These results are
      consistent with Hokanson's social learning theory of recovery from anger
      instigation and have important implications for research on emotion regulation
      and health.

PMID- 17532077
TI  - Dorsal root ganglion regulates the transient ERK activation in the dorsal horn of
      the spinal cord during development.
AB  - In the dorsal horn of the chick embryo spinal cord, extracellular signal
      regulated kinase (ERK) was phosphorylated transiently during embryonic days 6 and
      9. Co-culture studies suggested that dorsal root ganglion (DRG) activated ERK in
      the dorsal horn. Brain-derived neurotrophic factor (BDNF) activated ERK in the
      dorsal horn, and anti-BDNF blocked the DRG-induced ERK activation. These results
      suggest roles of BDNF in the DRG-induced ERK activation in the embryonic dorsal
      horn.

PMID- 17532078
TI  - Block copolymers and melt blends of polylactide with Nodax microbial polyesters:
      preparation and mechanical properties.
AB  - Completely renewable resource-based, degradable composites of poly(l-lactide) and
      Nodax [poly(3-hydroxybutyrate-co-3-hydroxyhexanoate)] were prepared by a melt
      blending procedure. oligoNodax-b-poly(l-lactide) diblock copolymers were
      synthesized and their use as compatibilizers in these melt blends was
      investigated. The block copolymers were prepared from microbially produced Nodax
      polyhydroxyalkanoate by a two-step transesterification and macroinitiator ring
      opening polymerization method. Addition of Nodax increased the notched Izod
      impact resistance of the binary blends compared to that of PLLA homopolymer (44+/
      6 J m(-1) versus 22+/-2 J m(-1), respectively). Further addition of the
      oligoNodax-b-poly(l-lactide) block copolymers to form ternary blends resulted in
      composites with improved dispersion and decreased Nodax particle size, but no
      additional improvement in the notched Izod impact properties. Significant Nodax
      degradation during processing coupled with a high Nodax entanglement molecular
      weight, as well as crystallization and low impact resistance of the Nodax
      dispersed phase are implicated as major factors impeding further toughening.

PMID- 17532079
TI  - Large-scale production and efficient recovery of PHB with desirable material
      properties, from the newly characterised Bacillus cereus SPV.
AB  - A newly characterised Bacillus strain, Bacillus cereus SPV was found to produce
      PHB at a concentration of 38% of its dry cell weight in shaken flask cultures,
      using glucose as the main carbon source. Polymer production was then scaled up to
      20 L batch fermentations where 29% dry cell weight of PHB was obtained within 48
      h. Following this, a simple glucose feeding strategy was developed and the cells
      accumulated 38% dry cell weight of PHB, an increase in the overall volumetric
      yield by 31% compared to the batch fermentation. Sporulation is the cause of low
      PHB productivity from the genus Bacillus [Wu, Q., Huang, H., Hu, G.H., Chen, J.,
      Ho, K.P., Chen, G.Q., 2001. Production of poly-3-hydroxybutyrate by Bacillus sp.
      JMa5 cultivated in molasses media. Antonie van Leeuwenhoek 80, 111-118]. However,
      in this study, acidic pH conditions (4.5-5.8) completely suppress sporulation, in
      accordance with Kominek and Halvorson [Kominek, L.A., Halvorson, H.O., 1965.
      Metabolism of poly-beta-hydroxybutyrate and acetoin in Bacillus cereus. J.
      Bacteriol. 90, 1251-1259], and result in an increase in the yield of PHB
      production. This observation emphasises the potential of the use of Bacillus in
      the commercial production of PHB and other PHAs. The recovery of the PHB produced
      was optimised and the isolated polymer characterised to identify its material
      properties. The polymer extracted, was found to have similar molecular weight,
      polydispersity index and lower crystallinity index than others reported in
      literature. Also, the extracted polymer was found to have desirable material
      properties for potential tissue engineering applications.

PMID- 17532080
TI  - Puumala and Tula hantaviruses in France.
AB  - The first genome sequences of Tula (TULV) and Puumala (PUUV) hantaviruses
      undoubtedly originated from France were recovered from tissue samples of European
      common voles and bank voles captured in Jura region. Genetic analysis of S and M
      segments of French PUUV strain revealed its highest similarity to strains from
      neighboring Belgium and Germany and also from Slovakia. On phylogenetic trees,
      French PUUV strain was placed within the central European lineage formed by
      strains from these three countries. Both of our French TULV strains clustered
      together and formed a distinct, well-supported genetic lineage.

PMID- 17532081
TI  - Immune response induced by spike protein from transmissible gastroenteritis
      coronavirus expressed in mouse mammary cells.
AB  - The present study is undertaken to investigate the immune response that was
      induced by the recombinant spike (S) protein from swine-transmissible
      gastroenteritis virus (TGEV) expressed in mouse mammary cells. A mammary-specific
      expression vector pEBS containing the full-length cDNA of S gene was constructed
      and expressed in the mouse mammary cells (EMT6). The recombinant S protein from
      culture supernatant of transgenic EMT6 was harvested and immunized BALB/c mice.
      The results demonstrated recombinant S protein was expressed at high levels in
      mammary cells by Western blotting and enzyme-linked immunosorbent assay (ELISA)
      detection. The antibody titer in BALB/c mice following immunization with
      recombinant S protein was detectable after the first immunization. Maximum titers
      of antibody (8.86+/-0.19 ng/ml of serum) were attained after the second
      immunization. In conclusion, the recombinant S protein expressed in mammary cells
      was able to elicit substantial immunological response against TGEV. This lays the
      basis for using mammary gland bioreactor generating edible vaccine.

PMID- 17532082
TI  - Up-regulation of IL-6 and TNF-alpha induced by SARS-coronavirus spike protein in
      murine macrophages via NF-kappaB pathway.
AB  - The clinical picture of severe acute respiratory syndrome (SARS) is characterized
      by an over-exuberant immune response with lung lymphomononuclear cells
      infilteration and proliferation that may account for tissue damage more than the
      direct effect of viral replication. To understand how cells response in the early
      stage of virus-host cell interaction, in this study, a purified recombinant S
      protein was studied for stimulating murine macrophages (RAW264.7) to produce
      proinflammatory cytokines (IL-6 and TNF-alpha) and chemokine IL-8. We found that
      direct induction of IL-6 and TNF-alpha release in the supernatant in a dose-,
      time-dependent manner and highly spike protein-specific, but no induction of IL-8
      was detected. Further experiments showed that IL-6 and TNF-alpha production were
      dependent on NF-kappaB, which was activated through I-kappaBalpha degradation.
      These results suggest that SARS-CoV spike protein may play an important role in
      the pathogenesis of SARS, especially in inflammation and high fever.

PMID- 17532084
TI  - Predictors of type 2 diabetes and diabetes-related hospitalisation in an
      Australian Aboriginal cohort.
AB  - Predictors of diabetes and diabetes-related hospitalisations were examined in 15
      88-year-old Aboriginal Australians (256 women, 258 men), surveyed in 1988-1989.
      Linkage to death records and hospitalisations to 2002 allowed proportional
      hazards or negative binomial modelling. Forty-five men (18%) and 59 women (24%)
      developed diabetes. Risk of diabetes was predicted positively by waist girth
      (hazard ratio (HR) 1.08, 95% CI 1.04, 1.13), smoking (HR 2.05, 95% CI 1.23, 3.39)
      and eating processed meats>4 times/month (HR 1.58, 95% CI 1.05, 2.40) and
      negatively by lower alcohol intake (HR 0.69, 95% CI 0.49, 0.99), preferring wine
      (HR 0.13, 95% CI 0.02, 0.97) and eating bush meats>4 times/month (HR 0.34, 95% CI
      0.13, 0.90). Hospitalisation was predicted positively by smoking (Incidence rate
      ratio (IRR) 3.72, 95% CI 1.70, 8.18) and eating processed meats (IRR 1.03, 95% CI
      1.01, 1.06), and negatively by exercise>or=once/week (IRR 0.23, 95% CI 0.08,
      0.65), eating bush meats (IRR 0.95, 95% CI 0.91, 0.99) and trimming fat from
      meats (IRR 0.53, 95% CI 0.30, 0.94). Length of hospital stay was predicted
      positively by eating processed meats (HR 1.76, 95% CI 1.23, 2.53) and added salt
      (HR 1.52, 95% CI 1.02, 2.26) and negatively by lower alcohol intake (HR 0.90, 95%
      CI 0.40, 0.92) and exercise (HR 0.66, 95% CI 0.46, 0.95). Central obesity and
      adverse lifestyle increase risk for diabetes or related hospitalisation among
      Aboriginal Australians.

PMID- 17532085
TI  - Prevalence of diabetes mellitus and its complications in a population-based
      sample in Al Ain, United Arab Emirates.
AB  - AIMS: To determine the prevalence of diabetes mellitus (DM) and its complications
      in the adult population of the United Arab Emirates (UAE) and assess the degree
      of metabolic control in subjects with diagnosed DM. METHODS: A random sample of
      houses of Emirati citizens living in Al Ain, UAE was surveyed. Fasting blood
      glucose was determined by glucose meter and an oral glucose tolerance test (OGTT)
      was conducted if blood sugar was <7 mmol/l. DM was defined according to the WHO
      criteria. Pre-diabetes status was based on fasting venous blood glucose
      concentration of 5.6-6.9 mmol/l or 2h post-OGTT venous blood glucose level of 7.8
      11.0 mmol/l. RESULTS: There were 2455 adults (>18) living in the 452 surveyed
      houses of which 10.2% reported having the diagnosis of DM. A total of 373 men and
      non-pregnant women underwent testing, and after adjustment for factors affecting
      participation probability the prevalence of diagnosed DM, undiagnosed DM and pre
      diabetes was 10.5, 6.6 and 20.2%, respectively. Age-standardized rates for DM
      (diagnosed and undiagnosed) and pre-diabetes among 30-64 years old were 29.0 and
      24.2%, respectively. Logistic regression analysis showed that only age and body
      mass index (BMI) were significantly independently related to undiagnosed DM. In
      patients with diagnosed DM, the prevalence rates for retinopathy, neuropathy,
      nephropathy, peripheral vascular disease and coronary heart disease were 54.2,
      34.7, 40.8, 11.1 and 10.5%, respectively. A significant proportion of subjects
      with undiagnosed DM and pre-diabetes also had micro- and macro-vascular
      complications. The proportion of subjects with diagnosed DM who achieved
      internationally recognized targets for HbA1c (<7%), LDL-C (<2.6 mmol/l) and blood
      pressure (<130/80 mmHg) was 33.3, 30.8 and 42.1%, respectively. CONCLUSION: This
      study confirms the previously reported high prevalence of DM in the UAE. Diabetic
      complications were highly prevalent among subjects with diagnosed and undiagnosed
      DM. Metabolic control was suboptimal in most subjects with diagnosed DM. Greater
      efforts are urgently needed to screen early and effectively treat DM in the UAE
      in order to prevent long-term complications.

PMID- 17532086
TI  - Factors responsible for the evolution of insulin resistance in Japanese type 2
      diabetic patients: association with atherosclerosis.
AB  - Type 2 diabetes is a heterogeneous syndrome characterized by defective insulin
      secretion and/or insulin resistance. In distinct from Caucasian populations,
      Japanese type 2 diabetic patients are divided into two categories: one with
      insulin resistance and the other with normal insulin sensitivity. This unique
      feature allows us to explore the factors responsible for the evolution of insulin
      resistance in Japanese type 2 diabetic patients. In this article, we describe the
      factors responsible for insulin resistance in Japanese type 2 diabetic patients
      and discuss the relationships between these factors and atherosclerosis. Japanese
      type 2 diabetic patients with insulin resistance had significantly higher
      concentrations of triglyceride, remnant-like particle cholesterol, subcutaneous
      and visceral abdominal fat areas, leptin, high sensitive C-reactive protein (hs
      CRP), and soluble E-selectin and lower concentration of adiponectin when compared
      to those with normal insulin sensitivity. There were, however, no significant
      difference in tumor necrosis factor (TNF)-alpha and soluble TNF receptors between
      the two groups. Serum triglyceride was positively correlated to visceral
      abdominal fat area, while serum leptin was positively correlated with
      subcutaneous abdominal fat area. In contrast, serum adiponectin was negatively
      correlated to visceral abdominal fat area. High sensitive CRP was positively
      correlated to BMI, triglyceride, and leptin, but was negatively correlated to
      adiponectin. Tumor necrosis factor-alpha and soluble TNF receptors, however, were
      not associated with any of these factors. Thus, it may be hypothesized that
      Japanese type 2 diabetic patients are divided into two categories: one with
      normal insulin sensitivity and the other with insulin resistance. The former
      group has a low cardiovascular risk factor, whereas the latter one has a markedly
      increased cardiovascular disease risk factor. Furthermore, abdominal fat related
      insulin resistance seems to be associated with insulin resistance in Japanese
      type 2 diabetic patients. In this section, we would like to focus on the factors
      contributing to insulin resistance and discuss the association of these factors
      with atherosclerosis in Japanese type 2 diabetic patients.

PMID- 17532087
TI  - Upregulation of hepatic angiotensin-converting enzyme 2 (ACE2) and angiotensin-(1
      7) levels in experimental biliary fibrosis.
AB  - BACKGROUND/AIMS: Angiotensin-converting enzyme 2 (ACE2), its product, angiotensin
      (1-7) and its receptor, Mas, may moderate the adverse effects of angiotensin II
      in liver disease. We examined the expression of these novel components of the
      renin angiotensin system (RAS) and the production and vasoactive effects of
      angiotensin-(1-7) in the bile duct ligated (BDL) rat. METHODS: BDL or sham
      operated rats were sacrificed at 1, 2, 3 and 4 weeks. Tissue and blood were
      collected for gene expression, enzyme activity and peptide measurements. In situ
      perfused livers were used to assess angiotensin peptide production and their
      effects on portal resistance. RESULTS: Hepatic ACE2 gene and activity (P<0.0005),
      plasma angiotensin-(1-7) (P<0.0005) and Mas receptor expression (P<0.01) were
      increased following BDL compared to shams. Perfusion experiments confirmed that
      BDL livers produced increased angiotensin-(1-7) (P<0.05) from angiotensin II and
      this was augmented (P<0.01) by ACE inhibition. Whilst angiotensin II increased
      vasoconstriction in cirrhotic livers, angiotensin-(1-7) had no effect on portal
      resistance. CONCLUSIONS: RAS activation in chronic liver injury is associated
      with upregulation of ACE2, Mas and hepatic conversion of angiotensin II to
      angiotensin-(1-7) leading to increased circulating angiotensin-(1-7). These
      results support the presence of an ACE2-angiotensin-(1-7)-Mas axis in liver
      injury which may counteract the effects of angiotensin II.

PMID- 17532088
TI  - A randomized trial of antioxidant therapy alone or with corticosteroids in acute
      alcoholic hepatitis.
AB  - BACKGROUND/AIMS: Oxidative stress is putatively involved in the pathogenesis of
      alcohol-induced liver injury. This trial was devised to determine whether
      antioxidant therapy, alone or as an adjunct to corticosteroids, improved survival
      in patients with acute alcoholic hepatitis. METHODS: Patients with a severe
      alcoholic hepatitis were stratified by sex and steroid use, and then randomized.
      The active group received N-acetylcysteine for one week, and vitamins A-E,
      biotin, selenium, zinc, manganese, copper, magnesium, folic acid and Coenzyme Q
      daily for 6 months. The trial was double blinded and placebo controlled. The
      primary end-point was mortality within 6 months. RESULTS: Thirty-six (20 male, 16
      female; mean discriminant function (DF) 86.6) received active drug, and 34 (18
      male, 16 female; mean DF 76.4) received placebo. 180-day survival was not
      significantly different between patients receiving drug and placebo (52.8% vs.
      55.8%, p=0.699). This was not affected by stratification for steroid use or sex.
      The only predictors of survival in multivariate analysis were initial bilirubin
      (p=0.017), white cell count (p=0.016) and age (p=0.037). Treatment allocation did
      not affect survival in multivariate analysis (p=0.830). CONCLUSIONS: Antioxidant
      therapy, alone or in combination with corticosteroids, does not improve 6-month
      survival in severe alcoholic hepatitis.

PMID- 17532089
TI  - Hyperammonemia acts synergistically with lipopolysaccharide in inducing changes
      in cerebral hemodynamics in rats anaesthetised with pentobarbital.
AB  - BACKGROUND/AIMS: The aim was to determine the effect of ammonia (NH(3)) and
      lipopolysaccharide (LPS) alone or in combination, on cerebral blood flow (CBF)
      and intracranial pressure (ICP) in the rat. Since amiloride-sensitive-ion
      pathways in the blood-brain barrier (BBB) modulate CBF, we also aimed to test if
      Na(+)/H(+)-inhibitors could prevent this possible synergism between NH(3) and
      LPS. METHODS: In experiment A, four groups of rats received ammonium acetate (140
      micromol/kg/min) or saline, each of them associated with either vehicle or LPS (2
      mg/kg). In experiments B and C, rats received similar treatments after having
      received amiloride (30 mg/kg) or 5-(N-methyl-N-isobutyl)-amiloride (MIA, 5
      mg/kg). Plasma tumor-necrosis-factor-alpha (TNF-alpha), ICP (via a cisterna magna
      catheter) and CBF (by laser-Doppler flowmetry) were measured. RESULTS: An
      increase in ICP and CBF within 60 min was observed only in rats that received
      NH(3) together with LPS as compared to any other group (P<0.01), which could be
      prevented by amiloride (P<0.05), but not by MIA. Both amiloride and MIA decreased
      the plasma TNF-alpha concentration. CONCLUSIONS: In rats anaesthetised with
      pentobarbital NH(3) infusion aggravates a LPS induced rise in ICP and induces an
      increase in CBF less clearly seen with LPS alone. This effect is prevented by the
      non-specific Na(+)/H(+) inhibitor amiloride, but not by MIA, a specific inhibitor
      of Na(+)/H(+) exchanger. Thus, the synergistic effect of NH(3) and LPS seems
      mediated by other amiloride-sensitive-ion-pathways in the BBB than the Na(+)/H(+)
      exchanger.

PMID- 17532090
TI  - A tracer metric numerical model for predicting tortuosity factors in three
      dimensional porous tissue scaffolds.
AB  - One of the critical functions of a tissue-engineered construct is to be able to
      provide adequate nutrient and oxygen supply into the interior of the construct.
      An insufficient supply will lead to slower cellular proliferation rates and
      eventual apoptosis. The supply of the nutrients is largely governed by the
      transport properties of the construct which in turn is dependent on the porosity,
      tortuosity and surface chemistry of the tissue construct. The design and
      fabrication of scaffolds with tailored properties is thus a crucial step in the
      growth of tissue within their host environment. This paper discusses the
      development of a numerical characterization technique to measure the three
      dimensional tortuosity factors for any given interconnected porous design.
      Tortuosity factors are obtained in the three orthogonal principal directions for
      several candidate unit cell architectures. The proposed numerical technique has
      been validated with models of known tortuosity. The developed technique will
      provide a basis for the study of transport properties of the designed scaffold
      and its effect on cellular function and response through the development of
      dynamic culture bioreactors.

PMID- 17532091
TI  - Chemotherapy with anticancer drugs encapsulated in solid lipid nanoparticles.
AB  - The prospect of improved cancer chemotherapy using solid lipid nanoparticles
      (SLN) as a drug delivery system is promising. Several obstacles frequently
      encountered with anticancer compounds, such as normal tissue toxicity, poor
      specificity and stability and a high incidence of drug-resistant tumor cells, are
      at least partially overcome by delivering them using SLN. The emergence of the
      newer forms of SLN such as polymer-lipid hybrid nanoparticles, nanostructured
      lipid carriers and long-circulating SLN may further expand the role of this
      versatile drug carrier in cancer treatment. This review focuses on the current
      use of SLN for the encapsulation and delivery of cytotoxic anticancer compounds.
      It also discusses more recent trends in the use of SLN as vehicles for delivery
      of chemosensitizers and cytotoxic therapeutic molecules. It is anticipated that,
      in the near future, SLN will be further improved to deliver anticancer compounds
      in a more efficient, specific and safer manner.

PMID- 17532092
TI  - Aberrant DNA methylation profiles of non-small cell lung cancers in a Korean
      population.
AB  - We performed this study to investigate the aberrant methylation profile of the
      cancer-related genes in Korean non-small cell lung cancer (NSCLC) that previously
      exhibited high frequencies of methylation in Western populations. The aberrant
      promoter methylation of eight genes (GSTP1, p16, FHIT, APC, RASSF1A, hMLH1,
      hMSH2, AGT) was determined by MSP in 99 surgically resected NSCLCs and their
      corresponding nonmalignant lung tissues. Methylation in the tumor samples was
      detected at 15% for GSTP1, 22% for p16, 34% for FHIT1, 48% for APC, 40% for
      RASSF1A, 18% for hMLH1, 8% for hMSH2 and 21% for AGT, whereas it occurred at
      lower frequencies in the corresponding nonmalignant lung tissues, particularly in
      the p16 (1%) and RASSF1A (1%) genes. These results suggest that the methylation
      profiles of NSCLCs in a Korean population are similar to those in Western
      populations.

PMID- 17532093
TI  - Mitochondrial clustering induced by overexpression of the mitochondrial fusion
      protein Mfn2 causes mitochondrial dysfunction and cell death.
AB  - Mitochondria change their shapes dynamically mainly through fission and fusion.
      Dynamin-related GTPases have been shown to mediate remodeling of mitochondrial
      membranes during these processes. One of these GTPases, mitofusin, is anchored at
      the outer mitochondrial membrane and mediates fusion of the outer membrane. We
      found that overexpression of a mitofusin isoform, Mfn2, drastically changes
      mitochondrial morphology, forming mitochondrial clusters. High-resolution
      microscopic examination indicated that the mitochondrial clusters consisted of
      small fragmented mitochondria. Inhibiting mitochondrial fission prevented the
      cluster formation, supporting the notion that mitochondrial clusters are formed
      by fission-mediated mitochondrial fragmentation and aggregation. Mitochondrial
      clusters displayed a decreased inner membrane potential and mitochondrial
      function, suggesting a functional compromise of small fragmented mitochondria
      produced by Mfn2 overexpression; however, mitochondrial clusters still retained
      mitochondrial DNA. We found that cells containing clustered mitochondria lost
      cytochrome c from mitochondria and underwent caspase-mediated apoptosis. These
      results demonstrate that mitochondrial deformation impairs mitochondrial
      function, leading to apoptotic cell death and suggest the presence of an
      intricate form-function relationship in mitochondria.

PMID- 17532094
TI  - Psoralen plus ultraviolet A does not increase the risk of cataracts: a 25-year
      prospective study.
AB  - BACKGROUND: In some animal species, exposure of the unprotected eye to psoralen
      plus ultraviolet A (PUVA) therapy induces lens opacities. The relevance of these
      animal findings to human beings is not established. However, some case reports
      suggest that PUVA in human beings may increase the risk of lens abnormalities.
      OBJECTIVE: Our aim was to evaluate any possible associations between exposure to
      PUVA and increased risk of ocular lens abnormalities. METHODS: Since 1977 the
      PUVA follow-up study has periodically monitored the ocular status of 1237 cohort
      members with psoriasis using structured eye examinations. In our previous report
      we presented data results of the first 10 years of prospective study. This report
      includes data from two additional cycles of eye examinations that span an
      additional 14 years of follow-up. RESULTS: Based on our data from the last pre
      1993 to final eye examination (2004), compared with that observed for the earlier
      period (first ever to last pre-1993 eye examination), the age-adjusted incidence
      of cataract did not increase significantly (incidence rate ratio = 1.04, 95%
      confidence interval = 0.82-1.31). In both the univariate and multivariate
      analyses increasing exposure to PUVA was not associated with a higher risk of
      cataract. LIMITATIONS: Our cohort principally enrolled middle-aged or older
      patients so our data do not permit us to assess the effects of PUVA on the eyes
      of younger persons. CONCLUSIONS: Increasing exposure to PUVA does not increase
      cataract risk among persons using eye protection at the rates used in our cohort.

PMID- 17532095
TI  - Contact allergy in oral disease.
AB  - BACKGROUND: The role of contact allergy in oral cavity disease processes is
      unknown. OBJECTIVE: We sought to determine the prevalence of contact allergy to
      flavorings, preservatives, dental acrylates, medications, and metals in patients
      with oral disease. METHODS: Patients were tested with an 85-item oral antigen
      screening series. Data were analyzed retrospectively. RESULTS: We evaluated 331
      patients with burning mouth syndrome, lichenoid tissue reaction, cheilitis,
      stomatitis, gingivitis, orofacial granulomatosis, perioral dermatitis, and
      recurrent aphthous stomatitis. Positive patch test results were identified in 148
      of the 331 patients; 90 patients had two or more positive reactions. Allergens
      with the highest positive reaction rates were potassium dicyanoaurate, nickel
      sulfate, and gold sodium thiosulfate. Of the 341 positive patch test reactions,
      221 were clinically relevant. LIMITATIONS: No follow-up data were available in
      this retrospective analysis. CONCLUSION: The positive and relevant allergic
      reactions to metals, fragrances, and preservatives indicated that contact allergy
      may affect oral disease.

PMID- 17532096
TI  - Chronic atrophic erosive dermatosis of the scalp and extremities: A
      recharacterization of erosive pustular dermatosis.
AB  - BACKGROUND: Erosive pustular dermatosis (EPD) is a rarely reported condition that
      primarily involves the actinically damaged scalp of elderly women. Although the
      condition is well recognized in the United Kingdom and Europe, no US cases have
      heretofore been reported. OBJECTIVES: We sought to document the presence, and
      determine the clinical characteristics, of EPD in the US population. METHODS:
      Patients were recruited from the dermatology clinic at a university in California
      and from the private practices of dermatologists in the Northern California
      region. RESULTS: Eleven patients with EPD were identified. Eight were women and 3
      were men. The scalp was involved in 9 patients and the extremities in two
      patients. The involved skin was actinically damaged in 9 patients. The patients
      were elderly (66-90 years) but one patient was a 15-year-old boy. All lesions
      resolved or greatly improved with the application of high-potency steroids or
      tacrolimus. LIMITATIONS: Not all patients were examined personally by the authors
      of this article. The length of follow-up was relatively short. CONCLUSIONS: EPD
      is a fairly common disease and is the most likely diagnosis in instances where
      chronic, nonhealing, shallow erosions occur on actinically damaged, or otherwise
      atrophic, skin. In spite of the name, intact pustules are rarely present. The
      histology is that of moderate to marked, nonspecific chronic inflammation. EPD
      responds well to high-potency topical steroids.

PMID- 17532097
TI  - In vitro and in vivo studies on UFP-112, a novel potent and long lasting agonist
      selective for the nociceptin/orphanin FQ receptor.
AB  - [(pF)Phe(4)Aib(7)Arg(14)Lys(15)]N/OFQ-NH(2) (UFP-112) has been designed as a
      novel ligand for the nociceptin/orphanin FQ (N/OFQ) peptide receptor (NOP) by
      combining into the same peptide different chemical modifications reported to
      increase N/OFQ potency. In vitro data obtained in the electrically stimulated
      mouse vas deferens demonstrated that UFP-112 behaved as a high potency (pEC(50)
      9.43) full agonist at the NOP receptor. UFP-112 effects were sensitive to the NOP
      antagonist UFP-101 but not to naloxone and no longer evident in tissues taken
      from NOP(-/-) mice. In vitro half life of UFP-112 in mouse plasma and brain
      homogenate was 2.6- and 3.5-fold higher than that of N/OFQ. In vivo, in the mouse
      tail withdrawal assay, UFP-112 (1-100pmol, i.c.v.) mimicked the actions of N/OFQ
      producing pronociceptive effects after i.c.v. administration and antinociceptive
      effects when given i.t.; in both cases, UFP-112 was approximately 100-fold more
      potent than the natural peptide and produced longer lasting effects. UFP-112 also
      mimicked the hyperphagic effect of N/OFQ producing a bell shaped dose response
      curve with the maximum reached at 10pmol. The hyperphagic effects of N/OFQ and
      UFP-112 were absent in NOP(-/-) mice. Equi-effective high doses of UFP-112
      (0.1nmol) and N/OFQ (10nmol) were injected i.c.v. in mice and spontaneous
      locomotor activity recorded for 16h. N/OFQ produced a clear inhibitory effect
      which lasted for 60min while UFP-112 elicited longer lasting effects (>6h). In
      conscious rats, UFP-112 (0.1 and 10nmol/kg, i.v.) produced a marked and sustained
      decrease in heart rate, blood pressure, and urinary sodium excretion and a
      profound increase in urine flow. Collectively, these findings demonstrate that
      UFP-112 behaves in vitro and in vivo as a highly potent and selective ligand able
      to produce full and long lasting activation of NOP receptors.

PMID- 17532098
TI  - Complete ascertainment of Parkinson disease in the Swedish Twin Registry.
AB  - This report describes the ascertainment of Parkinson disease (PD) in all
      individuals aged 50 years or older (49,814 individuals) from the Swedish Twin
      Registry. In phase one of the study, all twins were screened for PD using
      telephone interviews, with a response rate of 72.7%. In phase two, twins with
      suspected PD were re-contacted to exclude anyone from follow-up who reported
      parkinsonian symptoms due to diseases other than PD. In the third phase, in
      person clinical evaluations were completed for twins who were still considered PD
      suspects after phase two and for a sample of co-twins. During the clinical
      evaluations, we also collected blood samples and information about a variety of
      environmental exposures. Overall prevalence rate for PD was 496 per 100,000
      individuals. Among the 132 PD cases identified, there were only three concordant
      twin pairs. In total 7.2% of PD cases reported a first degree relative with PD.

PMID- 17532099
TI  - Synthesis of N-(5,7-diamino-3-phenyl-quinoxalin-2-yl)-3,4,5-substituted anilines
      and N-[4[(5,7-diamino-3-phenylquinoxalin-2-yl)amino]benzoyl]-l-glutamic acid
      diethyl ester: evaluation of in vitro anti-cancer and anti-folate activities.
AB  - Several diamino quinoxalines were designed, synthesized and evaluated as anti
      tumor agents. Two compounds showed the most potent cytotoxic activities against
      the leukemia CCRF-CEM cell line (GI(50)<0.01microM) and the ovarian cancer cell
      line OVCAR-4 (GI(50)=0.03microM), respectively, with comparable/better activities
      than Methotrexate (MTX). Docking calculations of the complexes of hDHFR with the
      most active compounds identified the binding mode of the described molecules with
      respect to MTX.

PMID- 17532100
TI  - [Two consecutive episodes of intracerebral hemorrhage as the presenting feature
      of polyarteritis nodosa].
AB  - We report a case of polyarteritis nodosa revealed by intracranial haemorrhage. A
      40-year-old woman presented two episodes of cerebral haemorrhage twelve days
      apart, the second due to an aneurysm rupture. The diagnosis of polyarteritis
      nodosa (PAN) was based on the following criteria: histological aneurysm
      examination, angiography suggesting PAN with cerebral, renal and splenic
      localizations, loss of weight and cutaneous nodules. Cerebral haemorrhage in PAN
      is rare and exceptionally the presenting feature of the disease.

PMID- 17532101
TI  - Safety, immunogenicity, and antibody persistence of a new meningococcal group A
      conjugate vaccine in healthy Indian adults.
AB  - We performed a double-blind, randomized, controlled phase I study to assess
      safety, immunogenicity, and antibody persistence of the new meningococcal group A
      conjugate vaccine (PsA-TT) in healthy volunteers aged 18-35 years. Of the 74 male
      subjects enrolled, 24 received the PsA-TT vaccine (Group 1), 25 received the
      Meningococcal Polysaccharide Vaccine A+C, Pasteur, Lyon, France (Group 2), and 25
      received the Tetanus Toxoid Vaccine Adsorbed, SIIL, Pune India (Group 3). No
      immediate reactions were observed. Local and systemic solicited reactions within
      7 days post-vaccination and unsolicited adverse events (AEs) were mild and
      similar among the three groups and resolved without sequelae. No serious AEs were
      notified up to 1 year post-vaccination. Four weeks post-vaccination, a slightly
      higher proportion of Group 1 subjects had a four-fold increase in SBA titers
      compared to Group 2 subjects (83% versus 72%, p>0.05). SBA GMTs in Groups 2 and 3
      were higher than in Group 3 (p<0.05). Serogroup A-specific IgG GMCs were
      significantly higher in Group 1 than in Groups 2 (p<0.05) and 3 (p<0.05). After 1
      year SBA titers were significantly higher in Group 1 than in Group 2 (p<0.05).
      The new PsA-TT vaccine was shown to be safe, immunogenic, and able to elicit
      persistent functional antibody titers in adults. This opens the prospective for
      further development and licensure of this vaccine to eliminate epidemic
      meningitis in sub-Saharan Africa.

PMID- 17532102
TI  - The effect of total knee replacement on dynamic support of the body during
      walking and stair ascent.
AB  - BACKGROUND: Little is known about the effects of total knee replacement surgery
      on the contributions of individual joint moments to the total support moment. A
      better understanding of these effects may enhance rehabilitation protocols and
      determine factors related to long-term surgical outcome. METHOD: Twenty-one
      subjects with total knee replacement and 21 controls performed level walking and
      stair ascent at two testing periods, pre- and 6 months post-surgery. Variables
      studied included gait velocity, stride length, knee flexion angle, net joint
      moments of the hip, knee and ankle, and total support moment. Data were analyzed
      at the first peak vertical ground reaction force. FINDINGS: For level walking,
      the total support moment, knee extensor moment, and knee flexion angle of total
      knee replacement patients were less than controls at post-surgery. For stair
      ascent, the patient group total support moment, ankle plantarflexor moment, and
      knee flexion angle were less than controls at both testing periods, while knee
      extensor moment was less than controls at post-surgery. Extensor synergies of the
      total knee replacement patients revealed less knee and more hip contributions
      during level walking and larger hip contributions during stair ascent to the
      total support moment than controls at both testing periods. INTERPRETATION: A
      feature of total knee replacement gait, pre- and post-surgery, is a stiff knee
      attitude which may serve to protect the quadriceps. The larger hip extensor
      contribution to the total support moment observed in the patients may compensate
      for the diminished knee extensor contribution during level walking and stair
      ascent.

PMID- 17532103
TI  - Comparison of solid-phase and eluate assays to gauge the ecotoxicological risk of
      organic wastes on soil organisms.
AB  - Development of methodologies to assess the safety of reusing polluted organic
      wastes in soil is a priority in Europe. In this study, and coupled with chemical
      analysis, seven organic wastes were subjected to different aquatic and soil
      bioassays. Tests were carried out with solid-phase waste and three different
      waste eluates (water, methanol, and dichloromethane). Solid-phase assays were
      indicated as the most suitable for waste testing not only in terms of relevance
      for real situations, but also because toxicity in eluates was generally not
      representative of the chronic effects in solid-phase. No general correlations
      were found between toxicity and waste pollutant burden, neither in solid-phase
      nor in eluate assays, showing the inability of chemical methods to predict the
      ecotoxicological risks of wastes. On the contrary, several physicochemical
      parameters reflecting the degree of low organic matter stability in wastes were
      the main contributors to the acute toxicity seen in collembolans and daphnids.

PMID- 17532104
TI  - Meaning as a mission: a review of empirical studies on appraisals of war and
      peacekeeping experiences.
AB  - The aim of this article is to review the scientific literature on making sense of
      war and peacekeeping experiences, and it includes an analysis of empirical
      studies that examine appraisals of military deployment experiences among
      veterans. Veterans reported more positive than negative effects in the studies of
      this review. Furthermore, construing positive meaning from war and peacekeeping
      experiences, especially related to combat exposure or high perceived threat, is
      associated with better psychological adjustment. More insight on "normal"
      psychological processing of stressful and traumatic experiences is obtained when
      the concept of meaning is used in research. This perspective emphasizes the
      perception of individuals and focuses on beliefs and attitudes in making sense of
      threatening events instead of pathologizing the response to trauma.

PMID- 17532106
TI  - Usefulness of long-acting injectable risperidone during 12-month maintenance
      therapy of bipolar disorder.
AB  - This study aimed to assess the safety, tolerability, efficacy, and compliance of
      a risperidone long-acting injection (RLAI) formulation for the maintenance
      treatment of stabilized bipolar patients. A prospective, open-label trial of RLAI
      was conducted for 12 months. Stable bipolar patients (n=11) were switched from
      their existing oral antipsychotic agents to RLAI, and injections were given every
      2 weeks. The assessments were performed at baseline and at 6 and 12 months of
      treatment by using the Young Mania Rating Scale (YMRS), Clinical Global
      Impressions-Severity of Illness (CGI-S) scale, 17-item Hamilton Rating Scale for
      Depression (HAM-D), Brief Psychiatric Rating Scale (BPRS), and Extrapyramidal
      Symptom Rating Scale (ESRS). The satisfaction levels of subjects were evaluated
      at the end of the study period using a 10-point visual analog scale. Ten patients
      (90.9%) completed the trial, and no significant changes were seen in the YMRS,
      HAM-D, and BPRS scores throughout the study. CGI-S and ESRS scores were
      significantly decreased from the baseline to the post-12-month treatment score.
      Relapses were not reported by any of the participants. This result indicates that
      RLAI may be beneficial in the maintenance therapy of stable bipolar patients;
      however, an adequately powered, randomized, placebo-controlled trial is necessary
      to draw a definite conclusion about the role of RLAI in the maintenance treatment
      of bipolar patients.

PMID- 17532105
TI  - Cognitive processes during fear acquisition and extinction in animals and humans:
      implications for exposure therapy of anxiety disorders.
AB  - Anxiety disorders are highly prevalent. Fear conditioning and extinction learning
      in animals often serve as simple models of fear acquisition and exposure therapy
      of anxiety disorders in humans. This article reviews the empirical and
      theoretical literature on cognitive processes in fear acquisition, extinction,
      and exposure therapy. It is concluded that exposure therapy is a form of
      cognitive intervention that specifically changes the expectancy of harm.
      Implications for therapy research are discussed.

PMID- 17532107
TI  - Clinical response of quetiapine in rapid cycling manic bipolar patients and
      lactate level changes in proton magnetic resonance spectroscopy.
AB  - The aim of the current study was to evaluate the relationship between
      quetiapine's effect on the improvement of mood symptoms in bipolar patients and
      brain metabolite level changes as measured by proton magnetic resonance
      spectroscopy ((1)H-MRS). Rapid cycling bipolar patients in the manic state were
      recruited and treated with quetiapine for 12 weeks. Clinical assessment was
      performed using the Young Mania Rating Scale (YMRS), the 17-item Hamilton
      Depression Rating Scale (HDRS) and the Clinical Global Impression-Severity scale
      (CGI-S) at baseline and weekly intervals during the 12-week period. In order to
      evaluate metabolite level changes over time, (1)H-MRS scans were acquired at
      baseline and week 12. There were significant reductions in YMRS scores (by
      43.0%), HDRS scores (by 27.5%) and CGI-S score (by 44.6%) over the 12 week
      period. Lactate levels significantly decreased over the 12-week study period
      (22.4%). This change in lactate levels was more prominent in quetiapine
      responders than in non-responders. Additionally, there was a positive correlation
      between changes in lactate levels and those in YMRS scores (r=0.52, p=0.003). Our
      findings suggest that quetiapine's antimanic and antidepressant efficacy in
      patients with rapid cycling bipolar disorder may potentially be related to
      decreased lactate levels in frontal regions of the brain.

PMID- 17532108
TI  - Dietary curcumin does not protect kidney in glycerol-induced acute renal failure.
AB  - Generation of reactive oxygen species significantly contribute to the
      pathogenesis of renal injury induced by myoglobin release. The present study was
      performed to investigate the effects of dietary curcumin, a natural antioxidant
      isolated from plant Curcuma longa, in an experimental model of myoglobinuric
      acute renal failure. Rats received curcumin at an oral dose of 100mg/kg/day for
      30 days. Renal injury was induced with injection of hypertonic glycerol (10 ml/kg
      50% solution) in hind limb muscle with blood urea of 57.8+/-7.2 vs. 7.72+/-1.03
      mmol/l and serum creatinine of 444.4+/-61.3 vs. 51.8+/-10.6 micromol/l, in
      glycerol-induced acute renal failure (ARF) vs. control rats, respectively. After
      48 h rats were sacrificed and thiobarbituric acid reactive substance (TBARS),
      glutathione, carbonyl content and kidney cortex brush border peptidase activities
      were determined in serum, kidney and liver. Rats that received curcumin in
      addition to glycerol had significantly lower TBARS in serum but not in kidney and
      liver. Carbonyl content in kidney and liver was significantly elevated in
      curcumin and glycerol treated rats and improved in animals treated with curcumin
      and glycerol together. The activities of kidney cortex enzymes, aminopeptidase N,
      angiotensinase A and dipeptidyl peptidase IV, were reduced in glycerol as well as
      in curcumin treated rats. The results obtained in this study provided additional
      evidence that despite its limited antioxidant activity curcumin did not protect
      kidney in myoglobinuric model of ARF.

PMID- 17532109
TI  - Effects of three biodiesels and a low sulfur diesel in male rats--a pilot 4-week
      oral study.
AB  - Because of the accessible and renewable nature of feedstock and the potential for
      the reduction of harmful combustion emissions and greenhouse gases, biodiesels
      have received increasing interest as an alternate fuel. Oral exposure to
      biodiesels is a concern because of contact during refuelling, accidental
      ingestion and exposure through ground water contamination. Although biodiesels
      from various feedstock are in use commercially and experimentally, very little is
      known about their potential adverse effects and no data is available on their
      potential for ground water contamination. A study was performed on male rats
      following oral treatment with experimental biodiesels (dissolved in corn oil)
      derived from canola oil (Bio-C), soy oil (Bio-S) and fish oil (Bio-F), at 500
      mg/kg body weight/day, 5 days per week, for 4 weeks. Separate groups of animals
      were treated with low sulfur diesel (LSD) for comparison purpose, and with corn
      oil alone to serve as control. The potential for ground water contamination by
      biodiesels was investigated by the preparation of water-accommodated fractions
      (WAF) followed by gas chromatographic analysis. WAF from Bio-F and Bio-S was
      found to have the highest level of dichloromethane extractable materials. Gas
      chromatographic analysis indicated that the extractable materials from biodiesels
      contained much higher proportion of C15-C30 materials than LSD. Increased liver
      weight was observed in animal treated with Bio-C, Bio-S and LSD and decreased
      thymus weight was found in those treated with Bio-S. Histopathological changes
      typical of male-rat specific hyaline-droplet nephropathy were detected in kidney
      tubules of animals treated with LSD, Bio-S and Bio-C. Mild adaptive changes were
      observed in thyroids of animals treated with LSD, Bio-S and Bio-F. Clinical
      chemical and biochemical changes were confined to Bio-S and LSD treated rats and
      included elevation in some hepatic phase-I and phase-II drug metabolizing enzymes
      and hepatic palmitoyl Co-A oxidase, and elevated urinary concentrations of
      ascorbic acid and albumin. At the given dose level of 500 mg/kg bw/day, the
      overall treatment-related effects of biodiesels and LSD are mild, and the
      severity of the treatment effects may be ranked as: LSD>Bio-S>Bio-C>Bio-F.
      Considered together with the presence of a higher level of water extractable
      materials, Bio-S may be more of a concern for potential human health than Bio-C
      and Bio-F in an oral exposure scenario. Further studies are needed to identify
      and characterize the constituents contributing to the treatment-related effects
      specific to these experimental biodiesels.

PMID- 17532110
TI  - 50 years ago: how prepared were our minds?
AB  - In 1956, when we started our collaboration, both Alick Isaacs and myself had done
      previous work on interference between inactive and active influenza viruses. We
      were aware of the state interference research had reached and of the two
      alternative explanations that had been envisaged.

PMID- 17532112
TI  - Anterior sacral meningocele misdiagnosed for an ovarian cyst.

PMID- 17532113
TI  - Inexact multistage stochastic integer programming for water resources management
      under uncertainty.
AB  - In this study, an inexact multistage stochastic integer programming (IMSIP)
      method is developed for water resources management under uncertainty. This method
      incorporates techniques of inexact optimization and multistage stochastic
      programming within an integer programming framework. It can deal with
      uncertainties expressed as both probabilities and discrete intervals, and reflect
      the dynamics in terms of decisions for water allocation through transactions at
      discrete points of a complete scenario set over a multistage context. Moreover,
      the IMSIP can facilitate analyses of the multiple policy scenarios that are
      associated with economic penalties when the promised targets are violated as well
      as the economies-of-scale in the costs for surplus water diversion. A case study
      is provided for demonstrating the applicability of the developed methodology. The
      results indicate that reasonable solutions have been generated for both binary
      and continuous variables. For all scenarios under consideration, corrective
      actions can be undertaken dynamically under various pre-regulated policies and
      can thus help minimize the penalties and costs. The IMSIP can help water
      resources managers to identify desired system designs against water shortage and
      for flood control with maximized economic benefit and minimized system-failure
      risk.

PMID- 17532111
TI  - Adenosine A2A receptors in ventral striatum, hypothalamus and nociceptive
      circuitry implications for drug addiction, sleep and pain.
AB  - Adenosine A2A receptors localized in the dorsal striatum are considered as a new
      target for the development of antiparkinsonian drugs. Co-administration of A2A
      receptor antagonists has shown a significant improvement of the effects of l
      DOPA. The present review emphasizes the possible application of A2A receptor
      antagonists in pathological conditions other than parkinsonism, including drug
      addiction, sleep disorders and pain. In addition to the dorsal striatum, the
      ventral striatum (nucleus accumbens) contains a high density of A2A receptors,
      which presynaptically and postsynaptically regulate glutamatergic transmission in
      the cortical glutamatergic projections to the nucleus accumbens. It is currently
      believed that molecular adaptations of the cortico-accumbens glutamatergic
      synapses are involved in compulsive drug seeking and relapse. Here we review
      recent experimental evidence suggesting that A2A antagonists could become new
      therapeutic agents for drug addiction. Morphological and functional studies have
      identified lower levels of A2A receptors in brain areas other than the striatum,
      such as the ventrolateral preoptic area of the hypothalamus, where adenosine
      plays an important role in sleep regulation. Although initially believed to be
      mostly dependent on A1 receptors, here we review recent studies that demonstrate
      that the somnogenic effects of adenosine are largely mediated by hypothalamic A2A
      receptors. A2A)receptor antagonists could therefore be considered as a possible
      treatment for narcolepsy and other sleep-related disorders. Finally, nociception
      is another adenosine-regulated neural function previously thought to mostly
      involve A1 receptors. Although there is some conflicting literature on the
      effects of agonists and antagonists, which may partly be due to the lack of
      selectivity of available drugs, the studies in A2A receptor knockout mice suggest
      that A2A receptor antagonists might have some therapeutic potential in pain
      states, in particular where high intensity stimuli are prevalent.

PMID- 17532115
TI  - Prospective validation of active surveillance in prostate cancer: the PRIAS
      study.

PMID- 17532116
TI  - The evaluation of cognitive functions with P300 test for chronic obstructive
      pulmonary disease patients in attack and stable period.
AB  - OBJECTIVES: Hypoxia, in chronic obstructive pulmonary disease (COPD), leads to a
      decrease in cerebral perfusion and an impairment of some cognitive abilities. We
      aimed to investigate the relation between arterial blood gas analysis (ABA) and
      pulmonary function test (PFT) parameters with cognitive function of COPD patients
      during attack and stable period. PATIENTS AND METHODS: ABA, PFT, P300 tests of 30
      patients in stabilized period and 30 patients in attack, and 17 healthy controls
      were evaluated. RESULTS: When both COPD groups and controls were compared, it was
      seen that latency of P300 was shorter in the control group (p<0.001), but there
      was no difference between COPD groups (p>0.05). P300 amplitude measures were
      lower in both COPD groups than control group, but it was not statistically
      significant (p>0.05). When we compared the measures of attack group, we saw that
      arterial oxygen tension (PaO(2)), arterial oxygen saturation (SaO(2)), forced
      expiratory volume in 1s (FEV(1)), FEV(1)/forced vital capacity (FVC) values
      increased (p<0.001), and P300 latency shortened (p<0.05) in attack group during
      stable period. P300 latency correlated significantly with PaO(2) (r=-0.557,
      p<0.001), SaO(2) (r=-0.424, p<0.001), FEV(1) (r=-0.441, p<0.001), FEV(1)/FVC (r=
      0.477, p<0.001) values, and age (r=0.329, p<0.05). P300 amplitude is only
      correlated with PaO(2) (r=0.236, p<0.05). CONCLUSION: Longer latency of P300
      appears to be an expected sequel of COPD. P300 test can be considered as a
      potential objective marker of cognitive impairment.

PMID- 17532117
TI  - Simulation of the cumulative effects of chemical spills using a spatial-temporal
      dynamics analysis algorithm.
AB  - Accidents in urban areas involving chemical spills demands development of not
      only feasible emergency strategies, but also a consistent framework to protect
      the environment and prevent accidents. This can be possible only by a sound
      understanding of the environmental impact of spills and their potential long-term
      effects. Furthermore, the impact assessment of chemical spills can not be done
      disregarding the spatial-temporal pattern of previous exposures reciprocally
      influenced by both chemical and environmental properties. In this context, this
      paper presents an analysis framework to quantify the cumulative effects of
      chemical spills at any given point of a certain area based on a "present" history
      of exposure coupled with chemical and environmental properties to predict
      possible scenarios of future exposure and estimate in advance potential alarming
      levels of pollution. In the present circumstances when increasing knowledge is
      required for an accurate prediction of spill migration through unsaturated soil,
      this paper proposes an algorithm capable of incorporating models of increasing
      complexities to simulate the single-spill events once new advancements in the
      field are taken. The algorithm developed is illustrated using a simple model with
      homogenous and steady-state conditions to simulate the single-spill events. A
      hypothetical case study was constructed to illustrate the analysis steps and the
      benefits of the algorithm.

PMID- 17532118
TI  - Peroxidation enhances the biogas production in the anaerobic digestion of
      biosolids.
AB  - During the anaerobic digestion of wastewater treatment sludge, commonly called
      biosolids, an energy rich biogas is formed which is now considered as renewable
      energy source and widely used for the production of heat and/or electricity. Pre
      treatment methods, which achieve a transformation of refractory COD into readily
      available and soluble BOD, have the potential to enhance the biogas-production.
      This paper studies several peroxidation techniques for this purpose: the well
      known Fenton peroxidation and novel reactions involving peroxymonosulphate (POMS)
      and dimethyldioxirane (DMDO). The results of the treatments show a considerable
      increase of COD and BOD in the sludge water, and an increase of the BOD/COD
      ratio. The biogas production was moreover seen to increase significantly. A
      maximum increase of 75% was measured with Fenton, while the POMS treatment
      increased the biogas production by a factor of nearly 2, against an even higher
      2.5 for the DMDO treatment. The methane content of the biogas remained between 65
      and 70%, thus maintaining its heating value.

PMID- 17532119
TI  - Apatite and Portland/apatite composite cements obtained using a hydrothermal
      method for retaining heavy metals.
AB  - Apatite and Portland/apatite composite cements containing steelwork dusts have
      been prepared using a low temperature hydrothermal method (200 degrees C, 48h).
      The produced solids were characterized by means of XRD, IR, and SEM-EDX, and the
      remaining liquid was analyzed by ICP. The results clearly show the capability of
      these cements to inertise the heavy metals contained in steelwork dusts, that is
      Fe, Pb, Mo, Cr, Mn, Ni, and Zn. In the case of apatitic cements, Fe, Mg, Cr, Mn,
      and Pb coming from steel dust replaced Ca in the divalent cation position of the
      apatite structure, while Si and Mo replaced P in tetrahedral position. The
      average crystal size of the apatite-containing dust is smaller than in pure
      apatite synthesized using the same procedure, which is related to the magnesium
      content of the dust, since magnesium seems to inhibit the crystal growth. XRD
      diagrams of composite cements show only peaks corresponding to phases observed in
      the single cements, and in that no new phases are found. However, EDX analysis
      reveals the introduction of cations coming from Portland cement into the apatite
      structure. From the results of water analysis it could be concluded that the
      capability of retention is higher in composite matrices than in the pure apatite
      one. In conclusion, the obtained data allow stating that the proposed method, the
      hydrothermal synthesis of steelwork dust containing cement, is a reliable one for
      immobilization of toxic residues containing heavy leachable cations.

PMID- 17532120
TI  - Effect of pH on solar photocatalytic reduction and deposition of Cu(II), Ni(II),
      Pb(II) and Zn(II): speciation modeling and reaction kinetics.
AB  - The present study is targeted on the effect of pH on solar photocatalytic removal
      of metal ions from wastewater. Photoreductive deposition and dark adsorption of
      metal ions Cu(II), Ni(II), Pb(II) and Zn(II), using solar energy irradiated
      TiO(2), has been investigated at pH values 2, 4, 7, 8 and 10. Modeling of metal
      species at the studied pH values has been performed and speciation is used as a
      tool for discussing the photodeposition. The decreasing order of metal deposition
      at pH 2 and 4 was found to be Pb(II)>Cu(II)>Ni(II) congruent with Zn(II). In the
      neutral and alkaline pH conditions (pH 7, 8 and 10) the order was
      Cu(II)>Zn(II)>Ni(II)>Pb(II).

PMID- 17532121
TI  - Photocatalytic oxidation of Cibacron Yellow LS-R.
AB  - The photocatalytic degradation of Cibacron Yellow LS-R (CIY), an azo dye, has
      been investigated in aqueous heterogeneous solutions containing semiconductor
      oxides as photocatalysts. The disappearance of the organic molecule follows
      approximately a pseudo-first kinetic order according to the Langmuir-Hinshelwood
      model. Various commercial photocatalysts are compared with respect to their
      decolorization efficiency, the COD, as well as the toxicity reduction. The effect
      of the temperature on the reaction rate is ascertained.

PMID- 17532122
TI  - A comparative study of ultrasonic cavitation and Fenton's reagent for bisphenol A
      degradation in deionised and natural waters.
AB  - Bisphenol A (BPA), a xenobiotic that exhibits endocrine disrupting action can be
      found in surface water. Its complete elimination can be obtained by advanced
      oxidation processes, notably upon the application of ultrasonic waves. In order
      to evaluate the feature of ultrasound relevance and the involvement of the
      hydroxyl radical in the BPA sonochemical degradation, ultrasound action was
      compared to Fenton's reaction in the cases of deionised acidic water (pH 3) and
      natural water (pH 7.6, main ions concentration: Ca(2+)=486mgL(-1), Na(+)=9.1mgL(
      1), Cl(-)=10mg L(-1), SO(4)(2-)=1187mgL(-1), HCO(3)(-)=402mgL(-1)). Ultrasound
      was performed at 300kHz and 80W. Fenton's process was operated using ferrous
      sulphate (100micromolL(-1)) and continuous H(2)O(2) addition at the rate as it is
      produced when sonication is applied in water in absence of substrate. Experiments
      carried out in deionised water show that both processes exhibit identical BPA
      elimination rate and identical primary intermediates. Main chemical pathways
      involve reactions with OH radical. Chemical oxygen demand (COD) and total organic
      carbon (TOC) analyses show that the Fenton's process is slightly more efficient
      than ultrasonic treatment for the removal of BPA by-products in the case of
      deionised water. Experiments conducted in natural water evidenced the inhibition
      of the Fenton process while the ultrasound action was not hampered.

PMID- 17532123
TI  - Electrochemical treatment of the pollutants generated in an ink-manufacturing
      process.
AB  - The effluents of ink-manufacturing processes contain a large variety of
      pollutants such as dyes, surfactants, biocides, water soluble solvents, etc. In
      this work, the electrochemical oxidation of several dyes (methylene blue and
      rhodamine B), solvents (monoethylene glycol, diethylene glycol and glycerol) and
      surfactants (sodium dodecylbenzenesulfonate) has been studied. To carry out the
      electrolyses, a bench-scale plant with a single-compartment electrochemical flow
      cell was used. Boron doped diamond (BDD) was used as anode and stainless steel
      (AISI 304) as cathode. For all the compounds tested, the conductive diamond
      electrooxidation allows achieving the almost complete removal of COD of the waste
      with a very high current efficiency. The efficiencies of the electrochemical
      processes seem to depend on the current density and on the nature of the anions
      contained in the waste (chlorine, sulphate, phosphate). Thus, it has been
      observed that the use of chloride media favours the treatment of dyes. On the
      contrary, the use of sulphate- or phosphate-containing solutions improves the
      removal of the aliphatic compounds studied (solvents). These results suggest an
      important role of the mediated electrochemical processes on the overall
      performance of the reaction system.

PMID- 17532124
TI  - Inactivation of E. coli, B. subtilis spores, and MS2, T4, and T7 phage using
      UV/H2O2 advanced oxidation.
AB  - The goal of this study was to evaluate the potential of an advanced oxidation
      process (AOP) for microbiocidal and virucidal inactivation. The viruses chosen
      for this study were bacteriophage MS2, T4, and T7. In addition, Bacillus subtilis
      spores and Escherichia coli were studied. By using H(2)O(2) in the presence of
      filtered ultraviolet (UV) irradiation (UV/H(2)O(2)) to generate wavelengths above
      295nm, the direct UV photolysis disinfection mechanism was minimized, while
      disinfection by H(2)O(2) was also negligible. Virus T4 and E. coli in phosphate
      buffered saline (PBS) were sensitive to >295nm filtered UV irradiation (without
      H(2)O(2)), while MS2 was very resistant. Addition of H(2)O(2) at 25mg/l in the
      presence of filtered UV irradiation over a 15min reaction time did not result in
      any additional disinfection of virus T4, while an additional one log inactivation
      for T7 and 2.5 logs for MS2 were obtained. With E. coli, only a slight additional
      effect was observed when H(2)O(2) was added. B. subtilis spores did not show any
      inactivation at any of the conditions used in this study. The OH radical exposure
      (CT value) was calculated to present the relationship between the hydroxyl
      radical dose and microbial inactivation.

PMID- 17532125
TI  - Photocatalytic degradation of phenol and phenolic compounds Part I. Adsorption
      and FTIR study.
AB  - With the goal of predicting the photocatalytic behaviour of different phenolic
      compounds (catechol, resorcinol, phenol, m-cresol and o-cresol), their adsorption
      and interaction types with the TiO(2) Degussa P-25 surface were studied. Langmuir
      and Freundlich isotherms were applied in the adsorption studies. The obtained
      results indicated that catechol adsorption is much higher than those of the other
      phenolics and its interaction occurs preferentially through the formation of a
      catecholate monodentate. Resorcinol and the cresols interact by means of hydrogen
      bonds through the hydroxyl group, and their adsorption is much lower than that of
      catechol. Finally, phenol showed an intermediate behaviour, with a Langmuir
      adsorption constant, K(L), much lower than that of catechol, but a similar
      interaction. The interaction of the selected molecules with the catalyst surface
      was evaluated by means of FTIR experiments, which allowed us to determine the
      probability of OH radical attack to the aromatic ring.

PMID- 17532126
TI  - Influence of clay mineral structure and surfactant nature on the adsorption
      capacity of surfactants by clays.
AB  - Adsorption of three surfactants of different nature, Triton X-100 (TX100) (non
      ionic), sodium dodecylsulphate (SDS) (anionic) and octadecyltrimethylammonium
      bromide (ODTMA) (cationic) by four layered (montmorillonite, illite, muscovite
      and kaolinite) and two non-layered (sepiolite and palygorskite) clay minerals was
      studied. The objective was to improve the understanding of surfactant behaviour
      in soils for the possible use of these compounds in remediation technologies of
      contaminated soils by toxic organic compounds. Adsorption isotherms were obtained
      using surfactant concentrations higher and lower than the critical micelle
      concentration (cmc). These isotherms showed different adsorption stages of the
      surfactants by the clay minerals, and were classified in different subgroups of
      the L-, S- or H-types. An increase in the adsorption of SDS and ODTMA by all clay
      minerals is observed up to the cmc of the surfactant in the equilibrium solution
      is reached. However, there was further TX100 adsorption when the equilibrium
      concentration was well above the cmc. Adsorption constants from Langmuir and
      Freundlich equations (TX100 and ODTMA) or Freundlich equation (SDS) were used to
      compare adsorption of different surfactants by clay minerals studied. These
      constants indicated the surfactant adsorption by clay minerals followed this
      order ODTMA>TX100>>SDS. The adsorption of TX100 and ODTMA was higher by
      montmorillonite and illite, and the adsorption of SDS was found to be higher by
      kaolinite and sepiolite. Results obtained show the influence of clay mineral
      structure and surfactant nature on the adsorption capacity of surfactants by
      clays, and they indicate the interest to consider the soil mineralogical
      composition when one surfactant have to be selected in order to establish more
      efficient strategies for the remediation of soils and water contaminated by toxic
      organic pollutants.

PMID- 17532127
TI  - Coupling solar photo-Fenton and biotreatment at industrial scale: main results of
      a demonstration plant.
AB  - This paper reports on the combined solar photo-Fenton/biological treatment of an
      industrial effluent (initial total organic carbon, TOC, around 500mgL(-1))
      containing a non-biodegradable organic substance (alpha-methylphenylglycine at
      500mgL(-1)), focusing on pilot plant tests performed for design of an industrial
      plant, the design itself and the plant layout. Pilot plant tests have
      demonstrated that biodegradability enhancement is closely related to
      disappearance of the parent compound, for which a certain illumination time and
      hydrogen peroxide consumption are required, working at pH 2.8 and adding
      Fe(2+)=20mgL(-1). Based on pilot plant results, an industrial plant with 100m(2)
      of CPC collectors for a 250L/h treatment capacity has been designed. The solar
      system discharges the wastewater (WW) pre-treated by photo-Fenton into a
      biotreatment based on an immobilized biomass reactor. First, results of the
      industrial plant are also presented, demonstrating that it is able to treat up to
      500Lh(-1) at an average solar ultraviolet radiation of 22.9Wm(-2), under the same
      conditions (pH, hydrogen peroxide consumption) tested in the pilot plant.

PMID- 17532128
TI  - Selective photocatalytic oxidation of steroid estrogens in water treatment: urea
      as co-pollutant.
AB  - The objective of the present research concerns the competitive photocatalytic
      oxidation (PCO) and adsorption of steroid estrogens (SEs) on titanium dioxide in
      presence of urea. The results showed the indifference of SEs towards the presence
      of urea in concentrations characteristic for the domestic sewage. The selective
      PCO of SEs appeared to be feasible in alkaline media, in which the PCO exhibited
      the highest efficiency. Ethanol used for hydrophobic SEs dissolution in water
      appeared to be interfering with the PCO.

PMID- 17532129
TI  - Photocatalytic degradation of NOx gases using TiO2-containing paint: a real scale
      study.
AB  - An indoor car park was appropriately equipped in order to test the de-polluting
      efficiency of a TiO(2)-containing paint in an indoor polluted environment, under
      real scale configuration. Depollution tests were performed in an artificially
      closed area of the parking, which was polluted by a car exhaust during the
      testing period. The ceiling surface of the car park was covered with white
      acrylic TiO(2)-containing paint (PP), which was developed in the frame of the EU
      project 'PICADA' (Photocatalytic Innovative Coverings Application for Depollution
      Assessment). The closed area was fed with car exhaust gases. As soon as the
      system reached steady state, the UV lamps were turned on for 5h. The difference
      between the final and the initial steady state concentration indicates the
      removal of the pollutants due to both the photocatalytic paint and car emission
      reduction. Results showed a significant photocatalytic oxidation of NO(x) gases.
      The photocatalytic removal of NO and NO(2) was calculated to 19% and 20%,
      respectively, while the photocatalytic rate (microgm(-2)s(-1)) ranged between
      0.05 and 0.13 for NO and between 0.09 and 0.16 for NO(2).

PMID- 17532130
TI  - Environmental green chemistry as defined by photocatalysis.
AB  - Photocatalysis is efficient in several fields. Firstly, in selective mild
      oxidation: oxidation of gas and liquid hydrocarbons (alkanes, alkenes, cyclo
      alkanes, aromatics) into aldehydes and ketons. Primary and secondary alcohols are
      also oxidized into their corresponding aldehydes or ketones. The high selectivity
      was ascribed to a photoactive neutral, atomic oxygen species. Once platinized
      (only 0.5wt.% Pt) titania may catalyze reactions involving hydrogen (deuterium
      alkane isotopic exchange and alcohol dehydrogenation). For fine chemicals, high
      initial selectivities enable titania to address most of the twelve principles of
      "green chemistry", such as the synthesis of 4-tert-butyl-benzaldehyde, an
      important intermediate in perfume industry by direct selective oxidation of 4
      tert-butyl-toluene with air. A new field recently appeared: thio-photocatalysis.
      Oxygen was replaced by sulfur, using H(2)S as a convenient and reactive source.
      For instance, the conversion of propene in 1-propanthiol was successfully
      obtained. The reaction was performed using either CdS or TiO(2). The latter was
      much more active than CdS. In environmental photocatalysis, titania becomes a
      total oxidation catalyst once in presence of water because of the photogeneration
      of OH radicals by neutralization of OH(-) surface groups by positive holes. Many
      toxic inorganic ions are oxidized in their harmless upper oxidized state. The
      total degradation of organic pollutants (pesticides, herbicides, insecticides,
      fungicides, dyes, etc. ...) is the main field of water photocatalytic
      decontamination. The UVA solar spectrum can de advantageously used as
      demonstrated by many campaigns performed in the solar pilot plant at the
      "Plataforma Solar de Almeria" (Spain).

PMID- 17532131
TI  - Isolation of lipase producing Bacillus sp. from olive mill wastewater and
      improving its enzyme activity.
AB  - The bacteria that could grow on media containing olive mill wastewater (OMW) were
      isolated and their lipase production capacities were investigated. The strain
      possessing the highest lipase activity among 17 strains grown on tributyrin agar
      medium was identified as Bacillus sp. The effect of initial pH on the lipase
      activity was investigated in tributyrin medium and pH 6 was found to be the
      optimal. The liquid medium composition was improved by replacing tributyrin with
      various carbon sources. Among the media containing different compositions of
      triolein, trimyristin, trilaurin, tricaprin, tricaprylin, tributyrin, triacetin,
      Tween 80, OMW, glucose, and whey; the medium contained 20% whey +1% triolein was
      found to give the highest lipase activity. Cultivation of Bacillus sp. in the
      optimal medium at pH 6 and 30 degrees C for 64h resulted in the extracellular and
      intracellular lipase activities of 15 and 168U/ml, respectively.

PMID- 17532132
TI  - Removal of an anionic dye by adsorption/precipitation processes using alkaline
      white mud.
AB  - Alkaline white mud (AWM) has been investigated as a low-cost material for removal
      of an anionic dye, acid blue 80. The effects of contact time, initial pH of dye
      solution, AWM dosage, and the presence of inorganic anion sulphate or phosphate
      ion on removal of the dye were evaluated. The results show that AWM could be used
      as an effective material for removal of acid blue 80 in a pre or main process,
      particularly at high dye concentration (>300 mgL(-1)), reaching maximum removal
      efficiency of 95%. At low dye concentration, surface adsorption is mainly
      responsible for the dye removal, while chemical precipitation of the dye anions
      with soluble Ca(2+) and Mg(2+) may play a dominant role for the dye removal at
      high concentration, producing much less sludge than conventional adsorption
      method. Solution pH has only a limited effect on the dye removal due to high
      alkalinity and large pH buffer capacity of AWM suspension and thereby pH is not a
      limiting factor in pursuing high dye removal. The presence of SO(4)(2-) could
      reduce the dye removal by AWM only when SO(4)(2-) concentration is beyond 0.7
      mmolL(-1). The dye removal may be significantly suppressed by the presence of
      phosphate with increasing concentration, and the reduction in the dye removal is
      much larger at high dye concentrations than at low ones.

PMID- 17532133
TI  - WITHDRAWN: Copper(II) preconcentration on Amberlite XAD-2010 loaded
      microorganisms prior to its spectrophotometric determination.
AB  - This article has been withdrawn consistent with Elsevier Policy on Article
      Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). The Publisher
      apologizes for any inconvenience this may cause.

PMID- 17532134
TI  - Hydrogen peroxide and oxygen-hydrogen oxidation of aromatic compounds in
      catalytic systems containing heteropoly compounds.
AB  - Hydrogen peroxide and Pt activated mixture of gaseous O(2) and H(2) have been
      applied to oxidation of aromatic compounds in the presence of redox active
      heteropoly compounds in the form of acid H(4)PMo(11)VO(40) and
      tetrabuthylammonium (TBA) salts TBA(4)PMo(11)VO(40) and TBA(4)HPW(11)Fe(OH)O(39).
      Benzene, toluene and phenol were subjected to hydroxylation of the ring, which
      was accompanied by secondary oxidation in the reaction with hydrogen peroxide.
      Oxygenation of toluene was equally directed to the ring and to methyl group. The
      total reactivity of substrates was increased in the order of
      benzene<toluene<phenol in oxidation by both O(2)/H(2) and H(2)O(2). Analysis of
      products yield and composition indicated the identical nature of active
      intermediates for both oxidants. It was suggested that HPC bonded radical species
      are responsible for the oxidation of hydrocarbons.

PMID- 17532135
TI  - Development and implementation of an MR-compatible whole body video system.
AB  - In conventional fMRI, the possibilities for remote visual monitoring of a
      volunteer or patient during scanning are very limited. However, performance
      during motor paradigms, monitoring of ventilated patients, or patients with
      movement disorders is often of particular interest. In order to facilitate remote
      visual monitoring during MRI examinations, an MR-compatible video system was
      developed and implemented to allow monitoring of the face and the body,
      separately, with two cameras. The system reliably allows the recording of video
      data during MRI scanning without affecting MR image quality. The applicability of
      the system for the online recording of tics during an fMRI study with Tourette
      patients is demonstrated. Monitoring of a motor task in healthy controls and
      Tourette patients was possible with exact synchronisation to the fMRI paradigm.
      Details of system set up and example control measurements are presented. Further,
      electronic and mechanical components are described in detail enabling easy
      reproduction of the system.

PMID- 17532136
TI  - Involvement of sigma-1 receptor modulation in the antidepressant action of
      venlafaxine.
AB  - Multiple lines of investigation have explored the role of sigma receptors in
      mental depression. Sigma receptors particularly, sigma-1 subtype is known to
      modulate the release of various catecholamines in the brain and may play, in some
      way, a role in the mechanism of action of various antidepressants. The present
      study investigated the possible involvement of sigma receptors in modulating the
      antidepressant-like effect of venlafaxine (dual serotonin and norepinephrine
      reuptake inhibitor) in the mouse forced swim test (FST). Immobility period in the
      forced swim test was registered for a total period of 6 min. Venlafaxine produced
      dose-dependent (4-16 mg/kg, i.p.) reduction in immobility period. Pretreatment of
      mice with (+)-pentazocine (2.5 mg/kg, i.p.), a high-affinity sigma-1 receptor
      agonist, produced synergism with subeffective dose of venlafaxine (2 mg/kg,
      i.p.). On the contrary, pretreatment with progesterone (10 mg/kg, s.c.), a sigma
      1 receptor antagonist neurosteroid, rimcazole (5 mg/kg, i.p.), another sigma-1
      receptor antagonist, or BD 1047 (1 mg/kg, i.p.), a novel sigma-1 receptor
      antagonist, reversed the anti-immobility effects of venlafaxine (8 mg/kg i.p.).
      The various modulators used in the study did not produce any changes in locomotor
      activity per se except venlafaxine which at higher dose (16 mg/kg, i.p.)
      significantly increased the locomotor activity in mice. The results for the first
      time demonstrated that the anti-immobility effects of venlafaxine in the FST
      possibly involve an interaction with sigma-1 receptors.

PMID- 17532137
TI  - Prenatal exposure to bisphenol A affects adult murine neocortical structure.
AB  - Prenatal exposure to low-doses of bisphenol A (BPA) has been shown to affect
      murine neocortical development by accelerating neuronal differentiation/migration
      through disrupting thyroid hormone function. We therefore studied whether
      prenatal exposure to low-doses of BPA affected organization of adult neocortical
      structures. Pregnant mice were injected with 20 microg/kg of BPA daily from
      embryonic day 0.5 (E0.5) and bromodeoxyuridine (BrdU) was injected at E12.5,
      E14.5 and at E16.5, and the fetal brains were analyzed after birth. The BrdU
      positive cells labeled at E14.5 were significantly increased in the Vth and VIth
      cortical layers of BPA-treated mice at postnatal 3 weeks (P3W), whereas they were
      confined to the IVth layer of control mice, though such differences disappeared
      at P12W. The thalamocortical projections demonstrated by DiI-labeling were
      abnormal at P3W and P12W in BPA-treated mice. These results indicate that BPA
      might affect not only neocortical development but also thalamocortical
      connections.

PMID- 17532138
TI  - What do the numbers mean? Normative data in chronic pain measures.
AB  - Although self-reported measures play a central role in the assessment of pain and
      its treatment, it has long been recognized that interpretation of these measures
      is severely limited by the absence of normative data. Despite that, relatively
      few of the measures used in pain clinics or research studies have normative data
      for reference. Using a pain centre sample (n=6124), this paper describes the
      development of a normative dataset on a number of commonly used pain-related
      measures. The measures cover many of the key dimensions in pain assessment,
      including pain severity/quality, disability (physical functioning), and mood
      (emotional functioning). Measures of different cognitive and coping constructs
      are also included. Mean scores are reported for each measure according to age
      group, gender, pain site, as well as percentiles for different scores for
      patients with chronic low back pain. The potential uses for datasets of this type
      include the assessment and evaluation of individual cases, as well as the
      interpretation of published clinical trials. It is also argued that future
      systematic reviews of pain treatments should include consideration of such
      patient characteristics as pain levels, disability and mood in the studies
      reviewed rather than pain site and chronicity alone.

PMID- 17532139
TI  - Tramadol and several anticonvulsants synergize in attenuating nerve injury
      induced allodynia.
AB  - Neuropathic pain results from injury or dysfunction of the central or peripheral
      nervous system. The treatment of neuropathic pain is challenging, in part because
      of its multiple etiologies. The present study explores combinations of the
      analgesic tramadol and each of four anticonvulsants in the treatment of
      surgically induced (ligation of the L5 spinal nerve) allodynia in rats. Each of
      the five drugs studied exhibited a dose-dependent antiallodynic effect. When
      studied in combination, tramadol and each of two of the anticonvulsants
      (topiramate and RWJ-333369) interacted synergistically at all three ratios
      studied, whereas tramadol and each of the other two anticonvulsants (gabapentin
      and lamotrigine) exhibited a synergistic antiallodynic effect at only one of
      three ratios investigated. In addition, tramadol and topiramate were found to
      interact synergistically in a nociceptive pain model, the mouse hot-plate test.
      These studies suggest the benefit of using combinations of analgesics and
      anticonvulsants in the relief of neuropathic pain.

PMID- 17532140
TI  - Accuracy of botulinum toxin injections in myofascial pain. Response to Gobel et
      al. Pain 2006;125:82-8.

PMID- 17532141
TI  - Emotional valence contributes to music-induced analgesia.
AB  - The capacity of music to soothe pain has been used in many traditional forms of
      medicine. Yet, the mechanisms underlying these effects have not been
      demonstrated. Here, we examine the possibility that the modulatory effect of
      music on pain is mediated by the valence (pleasant-unpleasant dimension) of the
      emotions induced. We report the effects of listening to pleasant and unpleasant
      music on thermal pain in healthy human volunteers. Eighteen participants
      evaluated the warmth or pain induced by 40.0, 45.5, 47.0 and 48.5 degrees C
      thermal stimulations applied to the skin of their forearm while listening to
      pleasant and unpleasant musical excerpts matched for their high level of arousal
      (relaxing-stimulating dimension). Compared to a silent control condition, only
      the pleasant excerpts produced highly significant reductions in both pain
      intensity and unpleasantness, demonstrating the effect of positive emotions
      induced by music on pain (Pairwise contrasts with silence: p's<0.001).
      Correlation analyses in the pleasant music condition further indicated that pain
      decreased significantly (p's<0.05) with increases in self-reports of music
      pleasantness. In contrast, the unpleasant excerpts did not modulate pain
      significantly, and warmth perception was not affected by the presence of pleasant
      or unpleasant music. Those results support the hypothesis that positive emotional
      valence contributes to music-induced analgesia. These findings call for the
      integration of music to current methods of pain control.

PMID- 17532142
TI  - The deconditioning paradigm for chronic low back pain unmasked?

PMID- 17532143
TI  - Detection of Leishmania infantum DNA by fret-based real-time PCR in urine from
      dogs with natural clinical leishmaniosis.
AB  - The aim of this study was to detect Leishmania infantum DNA by real-time PCR in
      urine from different groups of dogs with clinical leishmaniosis. Urine from 10
      clinically healthy dogs and 43 dogs with clinical leishmaniosis diagnosed by
      positive serology and/or bone marrow PCR were studied. The group of 43 dogs with
      clinical leishmaniosis was divided into three subgroups: 13 dogs with renal
      insufficiency and proteinuria (urine protein-creatinine ratio greater than one),
      13 dogs with only proteinuria, and 17 dogs with neither renal insufficiency nor
      proteinuria. The detection of Leishmania DNA was performed by light cycler real
      time PCR using hybridization probes in each urine sample. Leishmania positive PCR
      was found in 47% (20/43) of the urine from leishmaniotic dogs, while all urine
      from clinically healthy dogs were negative. The percentages of positive
      Leishmania PCR were 85% (11/13) in dogs with renal insufficiency and proteinuria,
      23% (3/13) in dogs with proteinuria and 35% (6/17) in dogs with neither renal
      insufficiency nor proteinuria. Dogs with renal insufficiency and proteinuria
      presented a statistical significant greater percentage of positive Leishmania PCR
      in urine when compared with the other subgroups (P<0.02). This study demonstrates
      the presence of Leishmania DNA in urine of dogs with leishmaniosis. Those dogs
      with severe renal damage present a greater number of Leishmania parasites in
      urine.

PMID- 17532144
TI  - Array-based functional screening for genes that regulate vascular endothelial
      differentiation of Flk1-positive progenitors derived from embryonic stem cells.
AB  - Functional genomics is a central topic of current biological research, where a
      reverse genetic approach is one of the most promising strategies to discover
      functions of novel genes. Such an approach requires high-throughput methodologies
      to assess biological functions for a huge number of genes. We have developed a
      transfection array that permits parallel introduction of multiple plasmids
      separately into living cells. The feasibility of this array was examined in an
      assay system. Eleven genes were over-expressed alone, or in combination in
      vascular progenitors derived from embryonic stem cells. Endothelial
      differentiation of the cells was monitored through a stably transformed EGFP
      reporter construct that is expressed only in endothelial cells. Transcriptional
      activators that promote endothelial differentiation, such as Ets1 and Sox7, were
      identified. In addition, the assays also revealed an inhibitory effect on
      endothelial differentiation by several of the factors. These results demonstrate
      the feasibility of the transfection array for use in cell-based, high-throughput
      functional assays.

PMID- 17532145
TI  - Intestinal and gastric tonometry during experimental burn shock.
AB  - INTRODUCTION: The occurrence of organ failure following thermal injury, despite
      restoration of hemodynamic parameters and urine output during resuscitation, has
      led to efforts to measure end-organ perfusion. The purpose of this 24-h study was
      to evaluate the utility of gastrointestinal (GI) tonometry during burn shock and
      resuscitation. METHODS: Male swine (n=11, 23.3+/-0.9 kg) were anesthetized with
      ketamine and propofol. A 70% full thickness burn was caused by immersion in 97
      degrees C water for 30 s. Resuscitation with lactated Ringer's, 4 ml/kg/% burn,
      was begun at hour 6 and titrated to urine output (UO). Arterial blood gases and
      pulmonary artery catheter data were measured every 6 h. Gastric and ileal
      regional PCO(2) (PrCO(2)) were measured continuously by air tonometry, and the
      gastric and ileal intramucosal pH (pHi) and PCO(2) gap (PrCO(2)-PaCO(2)) were
      calculated every 6 h. RESULTS: Gastric pHi, ileal PrCO(2), ileal pHi, and ileal
      PCO(2) gap (but not gastric PrCO(2) or PCO(2) gap) all decreased with shock and
      were restored to baseline levels by resuscitation. Changes in ileal PrCO(2) were
      of greater magnitude and demonstrated decreased variability than those in gastric
      PrCO(2). CONCLUSIONS: In this model, ileal tonometry outperformed gastric
      tonometry during burn shock and resuscitation.

PMID- 17532146
TI  - Inhalation injury: pathophysiology and clinical care proceedings of a symposium
      conducted at the Trauma Institute of San Antonio, San Antonio, TX, USA on 28
      March 2006.

PMID- 17532147
TI  - A clinical experience of treating exfoliative wounds using nanocrystalline silver
      containing dressings (Acticoat).

PMID- 17532148
TI  - Neurotrophin-3 administration alters neurotrophin, neurotrophin receptor and
      nestin mRNA expression in rat dorsal root ganglia following axotomy.
AB  - In the months following transection of adult rat peripheral nerve some sensory
      neurons undergo apoptosis. Two weeks after sciatic nerve transection some neurons
      in the L4 and L5 dorsal root ganglia begin to show immunoreactivity for nestin, a
      filament protein expressed by neuronal precursors and immature neurons, which is
      stimulated by neurotrophin-3 (NT-3) administration. The aim of this study was to
      examine whether NT-3 administration could be compensating for decreased
      production of neurotrophins or their receptors after axotomy, and to determine
      the effect on nestin synthesis. The levels of mRNA in the ipsilateral and
      contralateral L4 and L5 dorsal root ganglia were analyzed using real-time
      polymerase chain reaction, 1 day, 1, 2 and 4 weeks after unilateral sciatic nerve
      transection and NT-3 or vehicle administration via s.c. micro-osmotic pumps. In
      situ hybridization was used to identify which cells and neurons expressed mRNAs
      of interest, and the expression of full-length trkC and p75NTR protein was
      investigated using immunohistochemistry. Systemic NT-3 treatment increased the
      expression of brain-derived neurotrophic factor, nestin, trkA, trkB and trkC mRNA
      in ipsilateral ganglia compared with vehicle-treated animals. Some satellite
      cells surrounding neurons expressed trkA and trkC mRNA and trkC immunoreactivity.
      NT-3 administration did not affect neurotrophin mRNA levels in the contralateral
      ganglia, but decreased the expression of trkA mRNA and increased the expression
      of trkB mRNA and p75NTR mRNA and protein. These data suggest that systemically
      administered NT-3 may counteract the decrease, or even increase, neurotrophin
      responsiveness in both ipsi- and contralateral ganglia after nerve injury.

PMID- 17532149
TI  - Mycobacterial truncated hemoglobins: from genes to functions.
AB  - Infections caused by bacteria belonging to genus Mycobacterium are among the most
      challenging threats for human health. The ability of mycobacteria to persist in
      vivo in the presence of reactive nitrogen and oxygen species implies the presence
      in these bacteria of effective detoxification mechanisms. Mycobacterial truncated
      hemoglobins (trHbs) have recently been implicated in scavenging of reactive
      nitrogen species. Individual members from each trHb family (N, O, and P) can be
      present in the same mycobacterial species. The distinct features of the heme
      active site structure combined with different ligand binding properties and in
      vivo expression patterns of mycobacterial trHbs suggest that these globins may
      accomplish diverse functions. Here, recent genomic, structural and biochemical
      information on mycobacterial trHbs is reviewed, with the aim of providing further
      insights into the role of these globins in mycobacterial physiology.

PMID- 17532150
TI  - Protein fold and structure in the truncated (2/2) globin family.
AB  - Analysis of amino acids sequences and protein folds has recently unraveled the
      structural bases and details of several proteins from the recently discovered
      "truncated hemoglobin" family. The analysis here presented, in agreement with
      previous surveys, shows that truncated hemoglobins can be classified in three
      main groups, based on their structural properties. Crystallographic analyses have
      shown that all three groups adopt a 2-on-2 alpha-helical sandwich fold, resulting
      from apparent editing of the classical 3-on-3 alpha-helical sandwich of
      vertebrate and invertebrate conventional globins. Specific structural features
      distinguish each of the three groups. Among these, a protein matrix tunnel system
      is typical of group I, a Trp residue at the G8 topological site is conserved in
      groups II and III, and TyrB10 is almost invariant through the three groups. A
      strongly intertwined network of hydrogen bonds stabilizes the heme bound ligand,
      despite variability of the heme distal residues observed in the different
      proteins considered. Details of ligand recognition in the three groups are
      discussed at the light of residue conservation and of differing ligand diffusion
      pathways to the heme. Based on structural analyses of the family-specific fold,
      we endorse a recent proposal of leaving the "truncated hemoglobins" term, that
      does not represent properly the observed 2-on-2 alpha-helical sandwich fold, and
      adopting the simple "2/2Hb" term to concisely address this protein family.

PMID- 17532151
TI  - Changes in caecal microbiota and mucosal morphology of weaned pigs.
AB  - An experiment was designed to monitor the changes in caecal microbiota associated
      with early weaning. Twelve piglets (20+/-2 days) from six different litters were
      selected from a commercial source. For the two experimental groups, one animal
      from each litter was weaned onto a post-weaning diet (W) and the other remained
      with the sow (S). After 1 week, animals were sacrificed and caecal samples taken.
      Microbial counts for total bacteria, enterobacteria and lactobacilli populations
      were determined by quantitative PCR using SYBR Green dye. Microbial profiles were
      assessed by terminal restriction fragment length polymorphism (t-RFLP). Weaning
      promoted an increase in the enterobacteria:lactobacilli ratio (0.27 versus 1.67
      log/log 16S rRNA gene copy number, P=0.05). Total bacteria and richness of the
      caecal microbial ecosystem (number of peaks) were similar in both experimental
      groups (49.3 for S and 53.4 for W, respectively, P=0.22), although the band
      patterns were clearly grouped in two different clusters by dendogram analysis.
      Weaning was also associated with a decrease in crypt density, an increase in
      mytotic index and a decrease in the number of goblet cells. A reduced
      immunological response was also observed and was manifested by an increase in
      intraepithelial lymphocytes and lymphocyte density in the lamina propria. Weaning
      appears to be critical in the establishment of the caecal microbiota in pigs with
      important changes, particularly in microbial groups and in caecal mucosal
      architecture.

PMID- 17532152
TI  - Efficacy, safety, tolerability, and potential adverse effects of low-dose oral
      continuous combined menopausal hormone therapies, mostly double-blind clinical
      trials lasting for at least 2 years.

PMID- 17532153
TI  - Cell-polymer interactions of fluorescent polystyrene latex particles coated with
      thermosensitive poly(N-isopropylacrylamide) and poly(N-vinylcaprolactam) or
      grafted with poly(ethylene oxide)-macromonomer.
AB  - Cell-polymer interactions of thermosensitive poly(N-isopropylacrylamide) (PNIPAM)
      or poly(N-vinylcaprolactam) (PVCL) coated particles with RAW264.7 macrophages and
      intestinal Caco-2 cells were evaluated. Nanosized particles were prepared by
      modifying the surface of fluorescent polystyrene (FPS) particles with the
      thermosensitive polymer gels or with poly(ethylene oxide) (PEO)-macromonomer
      grafts. The particles were characterized by IR-spectroscopy for functional
      groups, light scattering for size distribution and zeta-potential for surface
      charge. Effects of temperature and polymer coating/grafting on the cellular
      interactions were evaluated by cell association/uptake and visualized by confocal
      scanning microscope. PEO and PNIPAM inhibited the polymer-cell contact by steric
      repulsion, evidenced by weak attachment of the particles. PVCL-coated FPS was
      adsorbed on the cells more strongly, especially at 37 degrees C, because of more
      hydrophobic nature at higher temperatures. The results suggest feasibility of the
      PNIPAM and PVCL for biotechnological/pharmaceutical applications, as the cell
      particle interactions may be modified by size, surface charge, hydrophobicity,
      steric repulsion and temperature.

PMID- 17532154
TI  - Prostaglandin E2 and interleukin-8 production in human epidermal keratinocytes
      exposed to marine lipid-based liposomes.
AB  - In response to exogenous stimuli such as non-sensitizing contact irritants, human
      keratinocytes produce various types of soluble pro-inflammatory mediators
      including prostaglandin E2 (PGE2) and interleukin 8 (IL-8). Polyunsaturated fatty
      acids of the n-3 series (n-3 PUFA) are known to play a role in the prevention of
      the inflammatory response. In this work, n-3 PUFA were supplied to keratinocytes
      through Marinosomes that are liposomes based on a natural marine lipid extract.
      Marinosomes contributed to reduce inflammation induced by croton oil by
      regulating PGE2 and IL-8 production in human keratinocyte cultures. However, the
      preventing effect of Marinosomes was highly dependent on the lipid concentration
      used and the liposome mean diameter.

PMID- 17532155
TI  - Transitiometric analysis of solid II/solid I transition in anhydrous
      theophylline.
AB  - For the first time, with the use of a high sensitivity, low heating rate,
      scanning transitiometry, it was possible to distinguish and characterise the
      polymorphic equilibrium transition between forms II and I in anhydrous
      theophylline. In this manner it was univocally proved, that forms II and I in
      theophylline are enantiotropically related. The temperature and enthalpy for that
      transition are as follows: T(trs)(II/I)=536.8+/-2.2K; Delta(trs)H(II/I)=1.99+/
      0.09 kJ/mol. Making use of advantages of very slow heating rate and of a high
      energetic sensitivity of the transitiometer it was possible to observe in detail
      the polymorphic transition followed by melting of high temperature form I and to
      stop the solid I-liquid transition at a desired point of equilibrium. Such a
      solid I-liquid equilibrium could be stabilised and then displaced back to the
      crystallisation of form I with an adequate use of a precise temperature
      programming. In such a way a pure single phase of form I of theophylline was
      prepared. This fact was confirmed by X-ray powder diffraction patterns and
      calorimetric traces of fusion of the crystallised product. The temperature and
      enthalpy of the form I-liquid transition are as follows: T(fus)(I)=546.5+/-0.2K
      and Delta(fus)H(I)=29.37+/-0.29 kJ/mol.

PMID- 17532156
TI  - Photoimages and the release characteristics of lipophilic matrix tablets
      containing highly water-soluble potassium citrate with high drug loadings.
AB  - Two types of the carnauba wax-based lipophilic matrix tablet using spray-dried
      granules (SDT) or directly compressible powdered mixtures (DCT) were prepared for
      sustained release. The model drug was a highly water-soluble potassium citrate
      and loaded about 74% of the total tablet weight. The SDT slowly eroded and
      disintegrated during the release study without showing sustained release when the
      hydrophilic excipients were added. In contrast, the DCT was more efficient for
      sustained release. The release rate decreased with increasing carnauba wax
      concentration. In particular, the sustained release rate was markedly pronounced
      when the lipophilic stearyl alcohol and stearic acid were combined with the
      carnauba wax. The surface of the intact DCT appeared to be smooth and rusty. The
      DCT rose to the surface from the bottom of the vessel during the release test,
      and numerous pores and cracks with no signs of disintegration were also observed
      after the release test. The release profile was dependent on the formulation
      composition and preparation method of the matrix tablet. Diffusion-controlled
      leaching through the channels of the pores and cracks of the lipophilic matrix
      tablet (DCT) is a key to the sustained release.

PMID- 17532157
TI  - Antimicrobial activity of the methanolic extracts and compounds from Treculia
      obovoidea (Moraceae).
AB  - The crude extract from Treculia obovoidea was subjected to purification by
      repeated chromatography. Eight compounds were isolated from Treculia obovoidea
      and identified as Psoralen (1), Bergapten (2), 7-methoxycoumarin (3), 7
      hydroxycoumarin (4), 4,2',4'-trihydroxychalcone (5), 4,2',4'-trihydroxy-3
      prenylchalcone (6), 3-hydroxy-4-methoxybenzoic acid (7) and O-[3-(2,2-dimethyl-3
      oxo-2H-furan-5-yl) butyl] bergaptol (8). These compounds together with the
      extract were tested for their antimicrobial activity against Gram-positive
      bacteria (six species), Gram-negative bacteria (12 species) and three Candida
      species using micro-dilution methods for the determination of the minimal
      inhibition concentration (MIC) and the minimal microbicidal concentration (MMC).
      The MIC values obtained with the crude extracts varied from 78.12 to 156.25
      microg/ml against 17 (80.95%) of the 21 tested microorganisms. All the isolated
      compounds showed selective activity. The antimicrobial activity of this plant as
      well as that of compounds 6 and 8 is being reported for the first time. The
      obtained results provide promising baseline information for the potential use of
      these crude extract as well as some of the isolated compounds in the treatment of
      bacterial and fungal infections.

PMID- 17532158
TI  - Effects of ayahuasca on psychometric measures of anxiety, panic-like and
      hopelessness in Santo Daime members.
AB  - The use of the hallucinogenic brew ayahuasca, obtained from infusing the shredded
      stalk of the malpighiaceous plant Banisteriopsis caapi with the leaves of other
      plants such as Psychotria viridis, is growing in urban centers of Europe, South
      and North America in the last several decades. Despite this diffusion, little is
      known about its effects on emotional states. The present study investigated the
      effects of ayahuasca on psychometric measures of anxiety, panic-like and
      hopelessness in members of the Santo Daime, an ayahuasca-using religion. Standard
      questionnaires were used to evaluate state-anxiety (STAI-state), trait-anxiety
      (STAI-trait), panic-like (ASI-R) and hopelessness (BHS) in participants that
      ingested ayahuasca for at least 10 consecutive years. The study was done in the
      Santo Daime church, where the questionnaires were administered 1h after the
      ingestion of the brew, in a double-blind, placebo-controlled procedure. While
      under the acute effects of ayahuasca, participants scored lower on the scales for
      panic and hopelessness related states. Ayahuasca ingestion did not modify state-
      or trait-anxiety. The results are discussed in terms of the possible use of
      ayahuasca in alleviating signs of hopelessness and panic-like related symptoms.

PMID- 17532159
TI  - 12 Y-STRs haplotypes in Chinese Naxi ethnic minority group.
AB  - Twelve Y-STRs loci including minimal haplotypes (DYS19, DYS389I, DYS389II,
      DYS390, DYS391, DYS392, DYS393, and DYS385a,b) and three additional loci, namely
      DYS437, DYS438 and DYS439 were co-amplified in 138 healthy unrelated males of
      Chinese Naxi ethnic minority group using the PowerPlex Y System. A total of 113
      haplotypes were identified, among which 103 were unique, and 6, 2, 1 and 1 were
      found in 2, 4, 5 and 10 individuals, respectively. The haplotype diversity for 12
      Y-STRs loci was 0.9923.The results from the present study can be used in forensic
      application and population genetics in the region, and can enrich Chinese
      ethnical genetic informational resources.

PMID- 17532160
TI  - Successful botulinum toxin treatment of dysphagia in a spinal muscular atrophy
      type 2 patient.
AB  - Prominent dysphagia is seen among patients with spinal muscular atrophy (SMA)
      type 2, especially at the late stage of their disease progression. Nasogastric
      tube feeding and gastrostomy are commonly utilized to maintain their nutritional
      status. However, choosing a treatment strategy to maintain appropriate
      nutritional status is often complicated by multiple factors, such as physical
      conditions and social aspects. We report a 21-year-old man with SMA type 2 who
      has been suffering from severe dysphagia. The findings at video-fluoroscopic
      swallow study (VSS) were consistent with a diagnosis of cricopharyngeal
      dysphagia. His dysphagia was successfully treated with percutaneous injection of
      botulinum toxin A (BTA) into the cricopharyngeal muscle. Our result demonstrates
      that administration of BTA is one of the effective treatment choices for
      dysphagia in SMA patients.

PMID- 17532161
TI  - Ischemic preconditioning is lost in aging hypertensive rat heart: independent
      effects of aging and longstanding hypertension.
AB  - Although in experimental hypertension the cardioprotective effects of ischemic
      preconditioning (PC) appear to be maintained, most studies have examined the
      short-term hypertension in juvenile animals. However, aging may be an additional
      factor that influences the effectiveness of PC. The aim of this study was to
      characterise the effects on PC of LVH and aging simultaneously. Hearts from
      spontaneously hypertensive rats (SHR) and age-matched normotensive Wistar-Kyoto
      rats (WKY) were studied. Excised hearts were Langendorff-perfused to give
      equivalent coronary flow per gram heart weight. The left main coronary artery was
      occluded for 35 min followed by 120 min reperfusion. Infarct size was determined
      by tetrazolium staining. Heart size was assessed as left ventricle/body weight
      ratio (LV/BW). PC was effected with 2 x 5 min periods of global ischemia prior to
      coronary occlusion. Hearts were studied at 3-4 months (juvenile), 7-8 months
      (mature) or 12-13 months (aging). LV/BW ratio in SHR increased relative to WKY
      controls by 20%, 32% and 40% in juvenile, mature and aging hearts, respectively,
      but ischemic risk zone size was similar in all groups (52-59% of LV). PC was
      equally effective at limiting infarct size in juvenile and mature SHR and WKY
      hearts but was ineffective in aging hearts from both WKY and SHR. Since
      angiotensin-converting enzyme inhibitors enhance sub-threshold PC in normal
      myocardium, we also examined the action of captopril (Cap) in aging hearts.
      Additional aging hearts received treatment with Cap 200 microM as an adjunct to
      PC. Although Cap+PC was able to induce modest protection in aging WKY hearts,
      this was not seen in aging SHR hearts. We conclude that PC is lost in
      longstanding hypertension through independent contributions of both hypertension
      and aging. These findings may have implications for the clinical development of
      preconditioning-based therapies since elderly patients with longstanding
      hypertension are at high risk of developing ischemic heart disease.

PMID- 17532162
TI  - Effect of PON1 polymorphism on HDL antioxidant potential is blunted with aging.
AB  - Paraoxonase1 is a HDL-associated enzyme, which is responsible for their
      antioxidant property. This study was aimed to investigate the effect of PON1
      [Q192R] and [L55M] genotypes on susceptibility of LDL and HDL to lipid
      peroxidation and on antioxidant activity of HDL as a function of aging. Seventy
      eight healthy subjects distributed in two age groups, young (20-30 years) and
      elderly (60-89 years) were recruited. PON1 activities and genotype polymorphisms
      were determined for each subject. LDL and HDL susceptibility to lipid
      peroxidation was evaluated by the measure of lag-phase (LP) for conjugated diene
      formation. HDL antioxidant property was evaluated by the measure of their
      capacity to protect LDL against lipid peroxidation. Our results show that LP for
      LDL and HDL peroxidation decreased with age of donors. Moreover, PON1 genotypes
      affect significantly the susceptibility of LDL and HDL to lipid peroxidation.
      Furthermore, basal- and salt-stimulated paraoxonase as well arylesterase
      activities were significantly reduced in elderly compared to young subjects.
      These results show a beneficial effect of PON1 towards susceptibility of HDL to
      oxidation as well to their antioxidant effect. However, this PON1 protective
      effect seems to be blunted with advancing age. Altogether our results suggest
      that the decrease in the PON1 protective effect with aging may contribute to the
      acceleration of the atherosclerosis process in elderly.

PMID- 17532163
TI  - The proteasome and its role in nuclear protein maintenance.
AB  - The cellular proteome is in a dynamic state of synthesis and degradation.
      Degradation of extracellular proteins is mainly mediated non-specifically by the
      lysosomes or due to released proteases, while the proteolysis of intracellular
      including nuclear proteins is catalyzed by the ubiquitin-proteasome pathway.
      Furthermore, the proteasomal system is largely responsible for the removal of
      unfolded and oxidatively damaged proteins. Taking into account the role of
      ubiquitin and proteasome system in protein metabolism, studies of its spatial
      organization within the cell are of great importance. For the understanding of
      cellular, including nuclear, protein maintenance the distribution of the
      proteasomes in both the nucleus and the cytosol and their response upon oxidative
      stress is of great interest. Although, the functional diversity of the cells is
      ensured by the three dimensional organization of the nucleus, nuclear proteins
      are also prone to oxidation and have to be removed from the cellular environment
      by the nuclear proteasome. Interestingly, nuclear proteins are partly degraded
      within the nucleus, whereas some are exported from the nucleus to the cytosol.
      Proteasomes are transported unidirectionally from the cytoplasm to the nucleus
      with a possible countervail during mitosis. This review is focused largely on the
      specifics of cellular proteasome distribution and on nuclear protein maintenance
      under physiological and oxidative stress conditions.

PMID- 17532164
TI  - Silicone mammary implants--can we turn back the time?
AB  - Mankind remains infatuated with finding the "fountain of youth'', and plastic
      surgery has become a very important component in the search for eternal youth.
      Invasive procedures such as face-lifts, body contouring, and implantation of
      silicone mammary implants (SMI) as well as less invasive procedures such as
      wrinkle decreasing protocols using filler substances or botulinum toxin,
      effectively reshape and rejuvenate the aging face or body. However, despite the
      improved cosmetic appearance of the individual, these treatments disrupt normal
      aging processes on cellular and molecular level. For example, silicone
      degradation products promote protein denaturation and activate cells of both the
      innate and adaptive immune system, thus perpetuating a chronic pro-inflammatory
      response of the local tissue. In this review, we concentrate on SMI and summarize
      the current clinical approaches, and the immunological and biochemical effects of
      those interventions.

PMID- 17532165
TI  - Intra- and inter-observer reliability of MRI examination of intervertebral disc
      abnormalities in patients with cervical myelopathy.
AB  - PURPOSE: Intervertebral cervical disc herniation (CDH) is a relatively common
      disorder that can coexist with degenerative changes to worsen cervicogenic
      myelopathy. Despite the frequent disc abnormalities found in asymptomatic
      populations, magnetic resonance imaging (MRI) is considered excellent at
      detecting cervical spine myelopathy (CSM) associated with disc abnormality. The
      objective of this study was to investigate the intra- and inter-observer
      reliability of MRI detection of CSM in subjects who also had co-existing
      intervertebral disc abnormalities. MATERIALS AND METHODS: Seven experienced
      radiologists reviewed twice the MRI of 10 patients with clinically and/or imaging
      determined myelopathy. MRI assessment was performed individually, with and
      without operational guidelines. A Fleiss Kappa statistic was used to evaluate the
      intra- and inter-observer agreement. RESULTS: The study found high intra-observer
      percent agreement but relatively low Kappa values on selected variables. Inter
      observer reliability was also low and neither observation was improved with
      operational guidelines. We believe that those low values may be associated with
      the base rate problem of Kappa. CONCLUSION: In conclusion, this study
      demonstrated high intra-observer percent agreement in MR examination for
      intervertebral disc abnormalities in patients with underlying cervical
      myelopathy, but differing levels of intra- and inter-observer Kappa agreement
      among seven radiologists.

PMID- 17532166
TI  - Partial splenic embolization using polyvinyl alcohol particles for hypersplenism
      in cirrhosis: a prospective randomized study.
AB  - PURPOSE: To prospectively evaluate the efficacy and safety of partial splenic
      embolization (PSE) using polyvinyl alcohol (PVA) particles for hypersplenism in
      cirrhosis, as compared to PSE using gelfoam particles. MATERIALS AND METHODS: PSE
      was performed in 60 consecutive patients with hypersplenism caused by cirrhosis.
      The patients were randomly assigned into 2 groups: gelfoam group, 32 patients
      received PSE using gelfoam particles as the embolic material; PVA group, 28
      patients received PSE using PVA particles. The follow-up contents included
      peripheral blood cell counts (leukocyte, platelet and red blood cell) and
      complications associated with PSE. RESULTS: Prior to PSE, there was no
      significant difference between the two groups in sex, age, Child-Pugh grade, the
      extent of embolization and peripheral blood cell counts. After PSE, no matter in
      which group, leukocyte and platelet counts kept significantly higher than pre-PSE
      during the 3-year follow-up period (P<.0001), but the post-PSE improvement of
      leukocyte and platelet counts was significantly better in PVA group than in
      gelfoam group (P<.05). Red blood cell counts showed no remarkable changes after
      PSE (P>.05). Severe complications occurred in 8 patients (25.0%) in gelfoam group
      and 6 patients (21.4%) in PVA group (P>.05), but the degree of abdominal pain was
      higher in the latter than in the former (P<.05). Among 17 patients who received
      more than 70% embolization of spleen, 10 (58.8%) developed severe complications,
      while among 43 patients who received 70% or less embolization of spleen, only
      four (9.3%) had severe complications. This difference was statistically
      significant (P<.05). CONCLUSION: PVA particles could be used as the embolic
      material in PSE; in comparison with PSE using gelfoam particles, PSE using PVA
      particles can achieve even better efficacy in alleviating hypersplenism, but the
      extent of embolization should be strictly limited to not more than 70% of splenic
      volume.

PMID- 17532167
TI  - Analytical methodologies for the determination of omeprazole: an overview.
AB  - Omeprazole, a gastric acid pump inhibitor, dose-dependently controls gastric acid
      secretion; the drug has greater antisecretory activity than histamine H(2)
      receptor antagonists. Omeprazole has been determined in formulations and
      biological fluids by a variety of methods such as spectrophotometry, high
      performance liquid chromatography with ultraviolet detection and liquid
      chromatography coupled with tandem mass spectrometry. The overview includes the
      most relevant analytical methodologies used in its determination since the origin
      still today.

PMID- 17532168
TI  - Use of liquid chromatography-mass spectrometry and a chemical cleavage reaction
      for the structure elucidation of a new sildenafil analogue detected as an
      adulterant in an herbal dietary supplement.
AB  - An herbal dietary supplement, marketed as a natural product for the enhancement
      of sexual function, was analyzed by HPLC with photodiode array and mass spectral
      detection and found to contain a compound related to the synthetic
      phosphodiesterase-5 (PDE-5) inhibitors. Based on UV spectra, mass spectra and
      direct infusion MS(n), the structure of the compound was tentatively identified
      as a sildenafil analogue in which the sulfonyl group had been replaced with an
      acetyl group. This new analogue is similar to acetildenafil, a previously
      reported sildenafil analogue, but differs in that it contains an N-methyl group
      where acetildenafil contains an N-ethyl group. The structure of the unknown was
      unequivocally established by chemical cleavage of the phenacylamine group of the
      molecule to generate N-methylpiperazine; other cleavage products matched those
      generated from acetildenafil. Since the new compound has one less CH(2) group
      than acetildenafil, it was named nor-acetildenafil.

PMID- 17532169
TI  - HPLC separation of naringin, neohesperidin and their C-2 epimers in commercial
      samples and herbal medicines.
AB  - Flavanone glycosides, such as naringin and neohesperidin, are distributed in some
      Citrus species and have a chiral center in the C-2 position of the flavanone
      moiety. Naringin and neohesperidin (2S-form) were separated from the
      corresponding C-2 epimers (2R-epi-form) by normal-phase HPLC using a
      polysaccaride-derived chiral stationary phases (CSPs), CHIRALPAK IB. The analyses
      of commercial samples of naringin revealed that the relative ratios of naringin
      to the C-2 epimer were 29-89%. In the case of a commercial sample of
      neohesperidin, the relative ratio of the neohesperidin (2S-form) is 84%. The HPLC
      application to Citrus species used as crude drugs in Japan (Kijitsu, Kikoku and
      Tohi) showed that the relative ratios of naringin to the C-2 epimer were 75-93%
      in Kijitsu, 74-79% in Kikoku and 54-64% in Tohi. However, there is a quite small
      ratio of the (2R)-epi-neohesperidin in Citrus. This result suggested that the
      averages of relative ratio of (2S)-naringin in Citrus species reduced according
      to the maturity of fruits (Kijitsu<Kikoku<Tohi). Since the relative ratios of
      (2S)-naringin of dry extracts of 5 Kampo formulations (including Kijitsu or
      Kikoku) decreased to 42-54%, the conversion from naringin to the (2R)-epimer
      might be enhanced during the decoction process of the formulations.

PMID- 17532170
TI  - Improved liquid chromatographic method for the simultaneous determination of
      tramadol and its three main metabolites in human plasma, urine and saliva.
AB  - Tramadol, an analgesic agent, and its main metabolites O-desmethyltramadol (M1),
      N-desmethyltramadol (M2) and O,N-didesmethyltramadol (M5) were determined
      simultaneously in human plasma, saliva and urine by a rapid and specific HPLC
      method. The sample preparation was a simple, one-step, extraction with ethyl
      acetate. Chromatographic separation was achieved with a Chromolith Performance RP
      18e 100 mm x 4.6 mm column, using a mixture of methanol:water (19:81, v/v)
      adjusted to pH 2.5 by phosphoric acid, in an isocratic mode at flow rate of 2
      ml/min. Fluorescence detection (lambda(ex) 200 nm/lambda(em) 301 nm) was used.
      The calibration curves were linear (r(2)>0.996) in the concentration ranges in
      plasma, saliva and urine. The lower limit of quantification was 2.5 ng/ml for all
      compounds. The within- and between-day precisions in the measurement of QC
      samples at four tested concentrations were acceptable in all analyzed body fluids
      The developed procedure was applied to assess the pharmacokinetics of tramadol
      and its main metabolites following administration of 100mg single oral dose of
      tramadol to healthy volunteers.

PMID- 17532171
TI  - An oncoplastic procedure for central and medio-cranial breast cancer.
AB  - Breast conserving therapy shows remarkable oncologic results and is eligible for
      up to 73% of patients with breast cancer. Cosmetic results are good, however, in
      patients with central or medio-cranial ("no-man's land") located breast cancer,
      the cosmetic result may be unsatisfying. The use of different breast reduction
      techniques have been shown to increase resection free margins and improve
      cosmetic results. We report here about the use of the Hall Findlay breast
      reduction technique for oncoplastic surgery to improve the cosmetic result in 11
      patients. The Hall Findlay technique shows good postoperative breast symmetry,
      all patients had resection free margins above 5mm and are free of disease at a
      mean follow-up of 12 months. The technique may be used for breast cancer at
      various locations and reduces scar visibility and morbidity.

PMID- 17532172
TI  - The feasibility of sentinel node biopsy in the previously treated breast.
AB  - PURPOSE: Sentinel lymph node biopsy (SNB) has been a standard technique in early
      breast cancer. However, it is not clear that the SNB procedure can be applied to
      second breast cancer or recurrence occurring in the previously treated breast.
      The purpose of this study was to clarify the feasibility of the SNB procedure in
      breast cancer occurring in the previously treated breast, and to investigate the
      factors related to altered lymphatic flow. PATIENTS AND METHODS: Between April
      2004 and December 2006, 1490 patients underwent the breast SNB procedure. Among
      them, 31 patients had a history of previous treatments in the same breast. Recent
      excision biopsy cases were not included in this group. All patients had previous
      breast-conserving surgery in the same breast. Sixteen patients had axillary
      dissection, 3 had SNB, and 12 had no axillary treatment. Ten patients had
      received radiation therapy to the breast and axilla. Visualization of axillary
      nodes, internal mammary nodes and contralateral axillary nodes was evaluated and
      compared with pathological results. RESULTS: Axillary nodes were visualized in 23
      patients, internal mammary nodes in 7 patients, and contralateral axillary nodes
      in 7 patients. The patients with previous axillary dissection exhibited altered
      lymph node distribution, but did not show involvement of contralateral axillary
      nodes. Visualization of contralateral axillary nodes occurred in 7 of the 10
      patients with previous irradiation to breast irrespective of axillary dissection.
      Twenty-eight patients underwent SNB, 4 of whom showed cancer-positive nodes.
      Three patients were cancer-positive in non-ipsilateral axillary nodes (one
      patient showed positive opposite axillary node and two patients showed positive
      internal mammary nodes). CONCLUSION: Previous axillary dissection or irradiation
      to the breast greatly influences lymphatic flow. Irradiation to the breast may be
      a strong factor for the visualization of contralateral axillary nodes. Despite
      the frequent alteration of lymphatic flow, SNB seems to be feasible in secondary
      or recurrent breast cancer patients.

PMID- 17532173
TI  - Spectrum and prognostication of KIT and PDGFRA mutation in gastrointestinal
      stromal tumors.
AB  - AIMS: Recent studies reported various mutation rates in gastrointestinal stromal
      tumors (GISTs) and inconsistent prognostic value of mutation in GIST patients.
      Our purpose was to analyze the frequency and spectrum of KIT and PDFGRA in a
      large series study and to determine if the presence of mutation and mutation type
      serve as prognostic factors in GIST patients. METHODS: A total of 134 GISTs were
      subjected to mutation analysis of KIT (exons 9, 11, 13, and 17) and PDGFRA (exons
      10, 12, 14, and 18). Clinicopathologic characteristics and survivals were
      correlated to KIT mutation. RESULTS: Approximately 69% of GISTs had KIT/PDGFRA
      mutation in Taiwanese GIST patients, with 99% of mutations occurred in KIT and 1%
      occurred in PDGFRA. Mutation rate was significantly increased in GISTs with
      mitotic counts >5 per 50 high power fields (chi(2) test, p=0.045). However, KIT
      mutations, regardless of the location (exons 9 versus 11) and type (missense,
      insertion, and deletion, including deletion specifically involving codons 557 and
      558) of mutation, were not significantly associated with poor progression-free
      survivals. Comparing the overall survival in imatinib-treated patients, there was
      no significant difference between patients with exon 11 mutation and those with
      exon 9 mutation (p=0.473). CONCLUSIONS: GISTs were commonly associated with KIT
      mutation, but rarely associated with PDGFRA mutation in Taiwan. The presence of
      KIT mutation and mutation type was not significant prognostic factors in GIST
      patients without imatinib treatment, suggesting that there is no need to stratify
      GIST patients by mutation status in clinical trials of targeted therapy.

PMID- 17532174
TI  - Prospective integration of cultural consideration in biomedical research for
      patients with advanced cancer: recommendations from an international conference
      on malignant bowel obstruction in palliative care.
AB  - In the setting of an international conference on malignant bowel obstruction as a
      model for randomized controlled trials (RCTs) in palliative care, we discuss the
      importance of incorporating prospective cultural considerations into research
      design. The approach commonly used in biomedical research has traditionally
      valued the RCT as the ultimate "way of knowing" about how to best treat a medical
      condition. The foremost limitation of this approach is the lack of recognition of
      the impact of cultural viewpoints on research outcomes. We propose that interest
      relevant to cultural viewpoints should be emphasized in conceptualizing and
      interpreting research questions, designs, and results. In addition to recognizing
      our cultural biases as individuals and researchers, we recommend two major shifts
      in designing and implementing RCTs: 1) inclusion of a multidisciplinary team of
      researchers to inform the diversity of perspectives and expertise brought to the
      research, and 2) use of mixed methods of inquiry, reflecting both deductive and
      inductive modes of inference.

PMID- 17532175
TI  - About pain, opioids, and dialysis.

PMID- 17532176
TI  - Ethical issues in research to improve the management of malignant bowel
      obstruction: challenges and recommendations.
AB  - Research to improve the care of patients with malignant bowel obstruction (MBO)
      is urgently needed. In particular, there is an urgent need for high-quality
      descriptive research, including prospective cohort studies, as well as randomized
      controlled trials to define optimal management strategies. However, investigators
      and clinicians face numerous barriers in conducting high-quality research in this
      patient population. These barriers include lack of funding, difficulties in
      identifying eligible patients, and a variety of practical and methodological
      challenges of designing these studies. In addition, there are a variety of
      ethical challenges that arise in the design and conduct of studies of MBO and
      particularly in the conduct of clinical trials. In this article, we address four
      categories of ethical issues: study design, recruitment, informed consent, and
      Institutional Review Board review. For each, we outline salient issues and
      suggest recommendations for enhancing the ethics of MBO studies, including
      interventional trials.

PMID- 17532177
TI  - The processes by which persons with HIV-related peripheral neuropathy manage
      their symptoms: a qualitative study.
AB  - A variety of peripheral neuropathies occur throughout the course of HIV
      infection, with the most common peripheral nerve disorder of late HIV infection
      being distal symmetrical peripheral neuropathy (DSPN). Current management
      strategies often fail to achieve satisfactory pain relief. This study was
      designed to explore the everyday life experiences related to DSPN in persons with
      AIDS (PWAs) and the behaviors they initiate to alleviate the symptoms. A
      qualitative study using a grounded theory approach was used to better understand
      the impact DSPN has on PWAs. Many interventions were attempted and were
      ineffective; the effective ones were highly individualized. Emerging themes in
      the delimiting debilitation continuum included isolating the symptom cluster,
      inventing and testing interventions, and assimilating the annoyance. Results
      indicated a need for better DSPN assessment by nurses and teaching strategy
      development to manage the symptoms, and development of strategies to combat
      functional DSPN disabilities.

PMID- 17532179
TI  - The relationship between cancer-related fatigue and patient satisfaction with
      quality of life in cancer.
AB  - Fatigue affects a majority of patients undergoing cancer-related therapies. We
      conducted a study of 954 adult cancer patients presenting for treatment at our
      hospital between April 2001 and November 2004 to quantify the relationship
      between fatigue and patient satisfaction with quality of life (QoL). Fatigue was
      measured using the European Organization for Research and Treatment of Cancer
      Quality of Life Questionnaire fatigue subscale. Patient satisfaction with QoL was
      measured using the Ferrans and Powers Quality of Life Index (QLI). The
      relationship between fatigue and QLI was evaluated using univariate and
      multivariate linear regression after controlling for the effects of clinical and
      demographic factors. Of the 954 patients, 579 were females and 375 males, with a
      median age at presentation of 56 years (range 20-90 years). Sixty-six percent had
      failed prior treatment. The most common cancers were breast (26%), colorectal
      (19%), and lung (16%) cancers. After controlling for the effects of age and prior
      treatment history, every 10-unit increase in fatigue was statistically
      significantly associated with 1.5-, 0.22-, 0.77-, 0.27-, and 0.85-unit declines
      in QLI health and physical, social and economic, psychological and spiritual,
      family, and global function scores, respectively. Consequently, a 30-point
      increase in fatigue score correlates with a 4.5-point decline in QLI health
      functioning-a clinically significant decline. In our study, we found that fatigue
      is strongly associated with patient satisfaction with QoL independent of the
      effects of age and prior treatment history.

PMID- 17532180
TI  - Measuring outcomes in randomized prospective trials in palliative care.
AB  - Palliative care aims to improve the quality of life of patients and their
      families and reduce suffering from life-threatening illness. In assessing
      palliative care efficacy, researchers must consider a broad range of potential
      outcomes, including those experienced by the patient's family/caregivers,
      clinicians, and the health care system. The purpose of this article is to
      summarize the discussions and recommendations of an Outcomes Working Group
      convened to advance the palliative care research agenda, particularly in the
      context of randomized controlled trials. These recommendations address the
      conceptualization of palliative care outcomes, sources of outcomes data,
      application of outcome measures in clinical trials, and the methodological
      challenges to outcome measurement in palliative care populations. As other fields
      have developed and refined methodological approaches that address their
      particular research needs, palliative care researchers must do the same to answer
      important clinical questions in rigorous and credible ways.

PMID- 17532181
TI  - A new bioluminescent cellular assay to measure the transcriptional effects of
      chemicals that modulate the alpha-1 thyroid hormone receptor.
AB  - Interactions of environmental pollutants with the thyroid endocrine axis have
      received much attention especially because thyroid hormones (THs) play a major
      role in mammalian brain development. In order to screen for compounds that act on
      the triiodothyronine (T3) signaling pathway, we developed a new reporter gene
      assay expressing luciferase under the control of the TH receptor (TR). PC12 cells
      expressing the alpha1-isoform of TR of avian origin were stably transfected with
      a luciferase gene controlled by the SV40 promoter, and enhanced by a four-spaced
      direct repeat (DR4) thyroid response element (TRE). The resulting PC-DR-LUC cells
      were used to optimize a T3 assay in multiwell microplates. This assay was highly
      sensitive (30 pM T3) and reproducible, and responded as expected to TH analogues.
      Several halogenated phenolic (3,3',5,5'-tetrabromobisphenol A, 3,3',5,5'
      tetrachlorobisphenol A, 4-hydroxy-2',3,4',5,6'-pentachlorobiphenyl) and phenol
      (pentachlorophenol, 2,4,6-triiodophenol) compounds suspected of being thyroid
      disrupting environmental chemicals induced partial agonistic and/or complex
      competitive/uncompetitive antagonistic responses in PC-DR-LUC cells at micromolar
      concentrations. A cell viability test indicated that these effects were not
      related to cytotoxicity of the chemicals. These results suggest that the PC-DR
      LUC assay could be a valuable tool for the large-scale screening for thyroid
      receptor agonists and antagonists in vitro, and for detecting thyroid disruptors
      in the environment.

PMID- 17532182
TI  - Reaction time: An alternative method for assessing the effects of multiple
      sclerosis on information processing speed.
AB  - The ability of a newly developed measure of information processing to detect
      deficits in cognitive functioning associated with multiple sclerosis (MS) was
      investigated. The Computerized Tests of Information Processing (CTIP; Tombaugh,
      T., & Rees, L. (1999). Computerized Tests of Information Processing (CTIP).
      Unpublished test. Ottawa, Ontario, Canada: Carleton University) was administered
      to 60 clinically definite MS patients and 60 healthy controls. MS patients
      responded significantly slower than controls on the reaction time tests composing
      the CTIP. Moreover, as the CTIP tests became more difficult (i.e. as processing
      demands increased), the difference between the performances of the two groups
      progressively increased. These results suggest the CTIP is sensitive to the
      cognitive deficits observed in MS and that this measure has the potential to
      serve as a viable alternative to traditional measures of information processing
      speed currently in use with MS patients.

PMID- 17532183
TI  - Replication-associated purine asymmetry may contribute to strand-biased gene
      distribution.
AB  - Among prokaryotic genomes, the distribution of genes on the leading and lagging
      strands of the replication fork is known to be biased. Several hypotheses
      explaining this strand-biased gene distribution (SGD) have been proposed, but
      none have been tested or supported by sufficient data analyses. In this work we
      have analyzed 211 prokaryotic genomes in terms of compositional strand
      asymmetries and the presence or absence of polC and have found that SGD
      correlates not only with polC, but also with purine asymmetry (PAS). Furthermore,
      SGD, PAS, and polC are all features associated with a group of low-GC, gram
      positive bacteria (Firmicutes). We conclude that PAS is a characteristic of
      organisms with a heterodimeric DNA polymerase III alpha-subunit constituted by
      polC and dnaE, which may play a direct role in the maintenance of SGD.

PMID- 17532184
TI  - Polymorphism of the KAP1.1, KAP1.3 and K33 genes in Merino sheep.
AB  - The wool fibre is a complex structure composed primarily of proteins from the
      keratin family. These proteins are responsible for the major structural and
      mechanical properties of the wool fibre. This study examines variation in the
      genes encoding key keratin (K) and keratin-associated proteins (KAP) in Merino
      sheep. Variation at these loci has the potential to be developed as genetic
      markers associated with wool traits. This study used 1541 Merino lambs born to 40
      sires sourced from three farms in the South Island of New Zealand. Polymerase
      chain reaction-single strand conformational polymorphism (PCR-SSCP) analysis was
      used to identify sequence variation in the KAP1.3 (formerly known as B2C) and K33
      (formerly known as KRT1.2) genes, whereas PCR-agarose gel electrophoresis was
      used to identify length polymorphism in the KAP1.1 (formerly known as B2A) gene.
      All allelic variation was confirmed by DNA sequencing. We report three alleles at
      the KAP1.1 locus, nine alleles at the KAP1.3 locus and five alleles at the K33
      locus of Merino sheep.

PMID- 17532185
TI  - PCR tools for the verification of the specific identity of ascaridoid nematodes
      from dogs and cats.
AB  - Based on the sequences of the internal transcribed spacers (ITS-1 and ITS-2) of
      nuclear ribosomal DNA (rDNA) of Toxocara canis, Toxocara cati, Toxocara
      malaysiensis and Toxascaris leonina, specific forward primers were designed in
      the ITS-1 or ITS-2 for each of the four ascaridoid species of dogs and cats.
      These primers were used individually together with a conserved primer in the
      large subunit of rDNA to amplify partial ITS-1 and/or ITS-2 of rDNA from 107 DNA
      samples from ascaridoids from dogs and cats in China, Australia, Malaysia,
      England and the Netherlands. This approach allowed their specific identification,
      with no amplicons being amplified from heterogeneous DNA samples, and sequencing
      confirmed the identity of the sequences amplified. The minimum amounts of DNA
      detectable using the PCR assays were 0.13-0.54ng. These PCR assays should provide
      useful tools for the diagnosis and molecular epidemiological investigations of
      toxocariasis in humans and animals.

PMID- 17532186
TI  - Identification of differentially expressed proteins in striatum of maneb-and
      paraquat-induced Parkinson's disease phenotype in mouse.
AB  - Behavioral, phenotypic and biochemical changes induced by maneb+paraquat (MB+PQ)
      in experimental animals have shown their role in the etiologies of Parkinson's
      disease (PD); however, MB+PQ induced neuronal damage at genome and proteome level
      have not yet been clearly understood. The present study was undertaken to
      investigate the differential protein expression patterns in control and MB+PQ
      treated mouse striatum and to identify differentially expressed proteins. Animals
      were treated with and without MB+PQ, twice a week for three, six and nine weeks
      and proteome profiles of striatum were compared. Three differentially expressed
      proteins were identified as complexin-I, alpha-enolase and glia maturation factor
      beta (GMF-beta) using 2D-PAGE and mass spectrometry. The differential expressions
      were also confirmed at transcription level by semi-quantitative RT-PCR. The
      results suggest the involvement of complexin-I, alpha-enolase and GMF-beta in
      MB+PQ induced PD phenotype in mouse.

PMID- 17532187
TI  - Phosphorylation and ubiquitination are necessary for Na,K-ATPase endocytosis
      during hypoxia.
AB  - As a cellular adaptative response, hypoxia decreases Na,K-ATPase activity by
      triggering the endocytosis of its alpha(1) subunit in alveolar epithelial cells.
      Here, we present evidence that the ubiquitin conjugating system is important in
      the Na,K-ATPase endocytosis during hypoxia and that ubiquitination of Na,K-ATPase
      alpha(1) subunit occurs at the basolateral membrane. Endocytosis and
      ubiquitination were prevented when the Ser 18 in the PKC phosphorylation motif of
      the Na,K-ATPase alpha(1) subunit was mutated to an alanine, suggesting that
      phosphorylation at Ser-18 is required for ubiquitination. Mutation of the four
      lysines surrounding Ser 18 to arginine prevented Na,K-ATPase ubiquitination and
      endocytosis during hypoxia; however, only one of them was sufficient to restore
      hypoxia-induced endocytosis. We provide evidence that ubiquitination plays an
      important role in cellular adaptation to hypoxia by regulating Na,K-ATPase
      alpha(1)-subunit endocytosis.

PMID- 17532188
TI  - Elevated social Internet use and schizotypal personality disorder in adolescents.
AB  - INTRODUCTION: In the past decade, the use of the Internet as a forum for
      communication has exponentially increased, and research indicates that excessive
      use is associated with psychiatric symptoms. The present study examined the rate
      of Internet use in adolescents with personality disorders, with a focus on
      schizotypal personality disorder (SPD), which is characterized by marked
      interpersonal deficits. Because the Internet provides an easily accessible forum
      for anonymous social interaction and constitutes an environment where
      communication is less likely to be hampered by interpersonal deficits, it was
      hypothesized that SPD youth will spend significantly more time engaging in social
      activities on the Internet than controls. METHODS: Self-reports of daily Internet
      use in adolescents with SPD (n=19), a control group with other personality
      disorders (n=22) and a non-psychiatric control group (n=28) were collected.
      RESULTS: Analyses revealed that the SPD participants reported significantly less
      social interaction with 'real-life' friends, but used the Internet for social
      interaction significantly more frequently than controls. Chat room participation,
      cooperative Internet gaming, and to a lesser degree, e-mail use, were positively
      correlated with ratings of SPD symptom severity and Beck Depression Inventory
      scores. DISCUSSION: Findings are discussed in light of the potential benefits and
      risks associated with Internet use by socially isolated SPD youth.

PMID- 17532189
TI  - No activation of urokinase plasminogen activator by anti-desmoglein 3 monoclonal
      IgG antibodies in cultured human keratinocytes.
AB  - BACKGROUND: Although pemphigus vulgaris (PV)-IgG has been shown to activate
      urokinase plasminogen activator (uPA) in cultured keratinocytes, activation of
      uPA is thought to have no primary role in PV-acantholysis, because PV-IgG is
      still pathogenic in uPA- and tissue-PA-knockout mice. OBJECTIVE: To determine if
      PV-IgG-induced uPA activation is due to specific antibody against Dsg3, we
      examined whether or not pathogenic monoclonal anti-Dsg3 antibody can activate
      uPA, because PV-IgG is thought to contain antibodies against unknown antigens
      besides Dsg3. METHODS: We stimulated cultured normal human and DJM-1
      keratinocytes with monoclonal anti-Dsg3 IgG1 antibodies (pathogenic AK23, AK19
      and nonpathogenic AK18, AK20), negative control monoclonal mouse IgG1 and
      positive control PV-IgG. Cells were treated with IgGs over a time course of 24h,
      and uPA-protein content and activity in the culture medium were determined by
      enzyme-linked immunosorbent assay (ELISA) and chromogenic assay, respectively.
      RESULTS: The uPA-protein content in samples treated with or without pathogenic,
      nonpathogenic, control monoclonal mouse IgG1s and PV-IgGs increased continuously
      up to 24h, with no differences between samples, suggesting a spontaneous
      secretion. In contrast, uPA activity in the culture medium of cells treated with
      PV-IgG increased dramatically, whereas that of cells treated with all AK-IgGs and
      control monoclonal mouse IgG1 did not increase at all. CONCLUSION: These results
      suggest that PV-IgG-dependent uPA activation is not related to anti-Dsg3 antibody
      activity, which is an essential factor in PV-IgG acantholysis, and that it may be
      due to other antigens than Dsg3 or unknown factors contained in PV-IgG fraction.

PMID- 17532190
TI  - Prevalence of streptogramin resistance in enterococci from animals:
      identification of vatD from animal sources in the USA.
AB  - There is considerable debate over the contribution of virginiamycin use in
      animals to quinupristin/dalfopristin (Q/D) resistance in humans. In this study,
      the prevalence and mechanisms of streptogramin resistance in enterococci from
      animals and the environment were investigated. From 2000-2004, enterococci from
      samples were tested for antimicrobial susceptibility. Q/D-resistant isolates
      (minimum inhibitory concentration >or=4 microg/mL) were subjected to polymerase
      chain reaction (PCR) using primers for streptogramin resistance genes (ermB,
      msrC, vatD and vatE). From the analysis, 1029/6227 (17%) Q/D-resistant non
      Enterococcus faecalis enterococci were identified. The majority of Q/D-resistant
      isolates were Enterococcus hirae (n=349; 34%), Enterococcus casseliflavus (n=271;
      26%) and Enterococcus faecium (n=259; 25%). Using PCR, 55.5% (n=571) were
      positive for ermB, 3% (n=34) for msrC, 2% (n=20) for vatE and 0.3% (n=3) for
      vatD; 39% (n=401) were negative for all four genes. The vatD-positive samples
      comprised two E. faecium from chicken and one E. hirae from swine. The nucleotide
      sequence of vatD from the three isolates was 100% homologous to published vatD
      sequences. These data indicate that Q/D resistance among enterococci from animals
      remains low despite the long history of virginiamycin use. To date, this is the
      first report of vatD from enterococci in animals in the USA.

PMID- 17532191
TI  - Association study between the corticotropin-releasing hormone receptor 2 gene and
      suicidality in bipolar disorder.
AB  - Family, adoption and twin studies show that genetics influences suicidal
      behavior, but does not indicate specific susceptibility variants. Stress response
      is thought to be mediated by the corticotrophin-releasing hormone (CRH), which is
      known to be a regulator of the hypothalamic-pituitary-adrenal pathway (HPA).
      Alterations in HPA system have been related to impulsivity, aggression and
      suicidal behaviour, that are common features in Bipolar Disorder (BD). CRH is a
      hypothalamic factor that stimulates the pituitary gland. Two CRH receptors are
      known, CRHR1 and CRHR2. To search for markers conferring genetic susceptibility
      to suicide, we typed three polymorphisms of the CRHR2 gene, CRHR2(CA), CRHR2(GT),
      and CRHR2(GAT), in 312 families where at least one subject had DSM-IV bipolar
      disorder. Family based association analyses in the suicide attempters using FBAT
      yielded no difference in the distribution of the alleles for all three markers.
      HBAT analysis for quantitative measures on suicide-related traits showed
      association between haplotype 5-2-3 and higher severity. The current results show
      that haplotype variation at the CRHR2 locus is associated with suicidal
      behaviour. This is to our knowledge the first investigation on suicidal behavior
      and genetic variation at the CRHR2 locus, an important regulator of the HPA axis.

PMID- 17532192
TI  - Early regionalization of the otic placode and its regulation by the Notch
      signaling pathway.
AB  - Otic neuronal precursors are the first cells to be specified and do so in the
      anterior domain of the otic placode, the proneural domain. In the present study,
      we have explored the early events of otic proneural regionalization in relation
      to the activity of the Notch signaling pathway. The proneural domain was
      characterized by the expression of Sox3, Fgf10 and members of the Notch pathway
      such as Delta1, Hes5 and Lunatic Fringe. The complementary non-neural domain
      expressed two patterning genes, Lmx1b and Iroquois1, and the members of the Notch
      pathway, Serrate1 and Hairy1. Fate map studies and double injections with DiI/DiO
      showed that labeled cells remained confined to anterior or posterior territories
      with limited cell intermingling. To explore whether Notch signaling pathway plays
      a role in the initial regionalization of the otic placode, Notch activity was
      blocked by a gamma-secretase inhibitor (DAPT). Notch blockade induced the
      expansion of non-neural genes, Lmx1 and Iroquois1, into the proneural domain.
      Combined gene expression and DiI experiments showed that these effects were not
      due to migration of non-neural cells into the proneural domain, suggesting that
      Notch activity regulates the expression of non-neural genes. This was further
      confirmed by the electroporation of a dominant-negative form of the Mastermind
      like1 gene that caused the up-regulation of Lmx1 within the proneural domain. In
      addition, Notch pathway was involved in neuronal precursor selection, probably by
      a classical mechanism of lateral inhibition. We propose that the regionalization
      of the otic domain into a proneural and a non-neural territory is a very early
      event in otic development, and that Notch signaling activity is required to
      exclude the expression of non-neural genes from the proneural territory.

PMID- 17532193
TI  - Neural substrates of olfactory processing in schizophrenia patients and their
      healthy relatives.
AB  - Odorants represent powerful stimuli capable of eliciting various emotional
      responses. In schizophrenia patients and their non-affected relatives, olfactory
      and emotional functions are impaired, revealing a familial influence on these
      deficits. We aimed at determining the neural basis of emotional olfactory
      dysfunctions using odors of different emotional valence for mood induction and
      functional magnetic resonance imaging (fMRI) by comparing 13 schizophrenia
      patients, their non-affected brothers and 26 matched healthy controls. Blood
      oxygen-level-dependent (BOLD) effects and subjective mood changes were assessed
      during negative (rotten yeast), positive (vanilla) and neutral (ambient air)
      olfactory stimulation. Group comparisons of brain activation were performed in
      regions of interest. Subjective ratings were comparable between groups and
      indicated successful mood induction. However, during stimulation with the
      negative odor, hypofunctional activity emerged in regions of the right frontal
      and temporal cortex in the patients. A familial influence in the neural
      substrates of negative olfactory dysfunction was indicated by a similar reduced
      frontal brain activity in relatives. Dysfunctions therefore appeared to be
      located in regions involved in higher cognitive processes associated with
      olfaction. No familial influences were indicated for cerebral dysfunctions during
      positive olfactory stimulation. Results point to a differentiation between trait
      and state components in cerebral dysfunctions during emotional olfactory
      processing in schizophrenia.

PMID- 17532194
TI  - Interaction between PAMAM 4.5 dendrimer, cadmium and bovine serum albumin: a
      study using equilibrium dialysis, isothermal titration calorimetry, zeta
      potential and fluorescence.
AB  - Binding of Cd(2+) by PAMAM 4.5 dendrimer was studied by equilibrium dialysis,
      isothermal titration calorimetry and zeta-potential measurement. The following
      binding parameters were obtained: n=23.8+/-9.5, K(b)=4.7+/-0.9x10(3) in water;
      and n=41.3+/-13.4, K(b)=2.1+/-0.8x10(3) in 0.15 mol/l phosphate-buffered saline.
      The location of the bound Cd(2+) is discussed. The interactions between bovine
      serum albumin, PAMAM 4.5 dendrimer and cadmium were analyzed using fluorescence
      and equilibrium dialysis. The competition between Cd(2+) binding to BSA and PAMAM
      4.5 dendrimer was investigated. It is proposed that PAMAM 4.5 dendrimer could be
      successfully used for extracting Cd(2+) from aqueous solutions (environmental
      protection).

PMID- 17532195
TI  - Ionic strength-sensitive pullulan acetate nanoparticles (PAN) for intratumoral
      administration of radioisotope: ionic strength-dependent aggregation behavior and
      (99m)Technetium retention property.
AB  - In order to design an effective intratumoral radioisotope carrier, a self
      assembled nanoparticle evidencing ionic strength (IS)-sensitivity from a
      polysaccharide derivative (pullulan acetate nanoparticle (PAN)) was prepared via
      dialysis. The PAN had a spherical shape in a range of size of 50-130 nm and a low
      critical aggregation concentration (CAC) (<8 microg/mL). With increases in the IS
      of the dialysis media (IS(dia)), the CAC of PAN was reduced gradually and the
      rigidity of the hydrophobic core in PAN was increased. This suggests that the
      property of PAN was altered more hydrophobically at high IS values. The
      stabilities of PANs prepared from various IS(dia) were also monitored with
      changes in the turbidity and particle size in different IS solutions. In the case
      of PAN prepared at an IS(dia)=0.0, the turbidity was dramatically reduced with
      increasing IS due to the facilitation of aggregation between the particles,
      whereas in the other cases, these changes were negligible. This finding indicates
      that PAN prepared in distilled water (IS=0.0) can be readily injected as the
      consequence of its nano-size, and accumulates quickly, then remains in the tumor
      site for a considerable period (IS=0.15). In order to closely estimate the
      potential of PAN as a radioisotope carrier, the radioisotope labeling efficiency
      of PAN with no chelating agents was evaluated. PAN evidenced a high degree of
      (99m)Technetium ((99m)Tc) labeling efficiency (approximately 98%). The percentage
      retention rate (%RR) of the (99m)Tc-labeled PAN was significantly longer than
      that of the free (99m)Tc (p<0.05), due largely to PAN's IS-sensitivity. In
      conclusion, PAN may constitute a new approach to the achievement of maximal
      radioisotope efficiency with regard to intratumoral administration.

PMID- 17532196
TI  - Spumochlamys iliensis n.g. n. sp. (Testacealobosia, Microchlamyiidae) from
      Central Asia, with notes on the diversity of Microchlamys-like testate amoebae.
AB  - Spumochlamys iliensis n. g., n. sp. was isolated from a mineral pond in an arid,
      semi-desert region in Kazakhstan (Central Asia). This amoeba is covered with a
      plate-shaped, flexible organic spongious test. The thin membranous margin of this
      test extends ventrally to surround a flexible ventral aperture. In its
      morphological features and behaviour this amoeba is very similar to Microchlamys
      patella (Claparede and Lachmann, 1859) Cockerell, 1911, but differs from this
      species and from M. sylvatica Golemansky, Skarlato and Todorov, 1987 in the lack
      of an additional membrane separating the cell body from the test, a feature that
      can only be detected using electron microscopy. The presence of this membrane is
      considered to be a principal characteristic of the genus Microchlamys and family
      Microchlamyiidae; however, this conclusion was reached from the study of only two
      species. The data presented show a higher diversity of Microchlamys-like testate
      amoebae; we therefore suggest that the described species should be included in
      the family Microchlamyiidae with emendation of its diagnosis, but that a separate
      genus within this family should be established to accommodate it.

PMID- 17532197
TI  - Effects of TNFalpha on the human nasal mucosa in vivo.
AB  - BACKGROUND: TNFalpha is a cytokine that may contribute to the pathophysiology of
      airway inflammation. Inhalation of TNFalpha produces granulocyte recruitment and
      airway hyperresponsiveness in man. Anti-TNFalpha treatment may inhibit allergen
      induced plasma exudation in guinea-pig airways. Increased nasal mucosal output of
      TNFalpha has been demonstrated in allergic rhinitis, but the effect of TNFalpha
      on the human nasal mucosa has not been examined in vivo. OBJECTIVE: To examine
      effects of topical TNFalpha on the human nasal mucosa in vivo. METHODS: In a dose
      finding study, healthy subjects received intranasal TNFalpha (0-7.5 microg).
      Nasal lavages were carried out before as well as 10 min and 24 h post challenge
      and alpha(2)-macroglobulin was measured as an index of plasma exudation. In a
      second study, involving patients with allergic rhinitis examined out of season, a
      sham-controlled nasal challenge with TNFalpha (10 microg) was performed and
      followed 24 h later by an allergen challenge. Lavages were performed before the
      TNFalpha challenge, 24 h thereafter, and 10 min post allergen challenge. alpha(2)
      Macroglobulin, eosinophil cationic protein (ECP), myeloperoxidase (MPO), and IL-8
      were analyzed as indices of plasma exudation, eosinophil activity, neutrophil
      activity, and pro-inflammatory cytokine production, respectively. RESULTS: In the
      dose-finding study, TNFalpha produced significant increases in alpha(2)
      macroglobulin 24h post challenge (p<0.01). In allergic rhinitis, 10 microg of
      TNFalpha also produced this effect (p<0.01) as well as increases in ECP and IL-8
      (p<0.01). MPO was increased 24 h post challenge, but this change did not reach
      statistical significance. TNFalpha did not produce any acute effects and did not
      affect the responsiveness to allergen. CONCLUSION: The present study demonstrates
      that topical TNFalpha produces a human nasal inflammatory response. These data
      suggest a role of TNFalpha in nasal conditions characterized by mucosal
      inflammation.

PMID- 17532198
TI  - Nutritional status and long-term mortality in hospitalised patients with chronic
      obstructive pulmonary disease (COPD).
AB  - Patients with chronic obstructive pulmonary disease (COPD) often have
      difficulties with keeping their weight. The aim of this investigation was to
      study nutritional status in hospitalised Nordic COPD patients and to investigate
      the association between nutritional status and long-term mortality in this
      patient group. In a multicentre study conducted at four university hospitals
      (Reykjavik, Uppsala, Tampere and Copenhagen) hospitalised patients with COPD were
      investigated. Patient height, weight and lung function was recorded. Health
      status was assessed with St. George's Hospital Respiratory Questionnaire. After 2
      years, mortality data was obtained from the national registers in each country.
      Of the 261 patients in the study 19% where underweight (BMI <20), 41% were of
      normal weight (BMI 20-25), 26% were overweight (BMI 25-30) and 14% were obese.
      FEV(1) was lowest in the underweight and highest in the overweight group
      (p=0.001) whereas the prevalence of diabetes and cardio-vascular co-morbidity
      went the opposite direction. Of the 261 patients 49 (19%) had died within 2
      years. The lowest mortality was found among the overweight patients, whereas
      underweight was related to increased overall mortality. The association between
      underweight in COPD-patients, and mortality remained significant after adjusting
      for possible confounders such as FEV(1) (hazard risk ratio (95% CI) 2.6 (1.3
      5.2)). We conclude that COPD patients that are underweight at admission to
      hospital have a higher risk of dying within the next 2 years. Further studies are
      needed in order to show whether identifying and treating weight loss and
      depletion of fat-free mass (FFM) is a way forward in improving the prognosis for
      hospitalised COPD patients.

PMID- 17532199
TI  - Respiratory symptoms and lung function in 30-year-old individuals with alpha-1
      antitrypsin deficiency.
AB  - INTRODUCTION: Individuals with severe alpha-1-antitrypsin (AAT) deficiency have a
      well-known risk of developing emphysema but it is not known at which age the
      first symptoms occur and lung function declines. The aim of this study was to
      examine the prevalence of smoking, respiratory symptoms and lung function at the
      age of 30 in AAT-deficient individuals (PiZ and PiSZ) identified by neonatal
      screening. MATERIAL AND METHODS: One hundred and seven PiZ, 45 PiSZ and 197
      control subjects (PiMM) filled in a questionnaire regarding smoking habits and
      symptoms. Ninety PiZ, 40 PiSZ and 84 control subjects underwent spirometry
      including FEV(1) and FVC. RESULTS: Twenty-one percent of PiZ, 23% of PiSZ and 34%
      of PiMM subjects had smoked at some time (p<0.05). Sixty-five percent of PiZ, 55%
      of PiSZ and 35% of PiMM ever-smokers reported shortness of breath on exertion
      (p<0.05 PiZ vs PiMM). The mean FEV(1) was 101% predicted (95% CI 98-104) in PiZ,
      101% predicted (95% CI 97-106) in PiSZ, and 96% predicted (95% 93-98) in PiMM
      individuals (p<0.05). There was no difference in mean FEV(1) when comparing ever-
      and neversmokers in the different Pi groups separately. CONCLUSION: At the age of
      30, the AAT-deficient individuals in this cohort report more symptoms than the
      control subjects. Smoking is less common in the cohort compared to controls.
      Their lung function is normal.

PMID- 17532200
TI  - NT-proBNP in chronic hypercapnic respiratory failure: a marker of disease
      severity, treatment effect and prognosis.
AB  - BACKGROUND: Natriuretic peptides are considered as reliable indicators of left
      heart failure (HF) and are useful for differential diagnosis of dyspnoea. AIM: We
      evaluated the clinical significance of N-terminal pro-brain natriuretic peptide
      (NT-proBNP) in patients with chronic hypercapnic respiratory failure (CHRF).
      METHODS: In 60 patients with CHRF, plasma concentrations of NT-proBNP were
      assessed at baseline and after treatment including non-invasive ventilation
      (NIV). The relationship of NT-proBNP to disease severity and its predictive value
      for survival were evaluated up to 4 years. RESULTS: NT-proBNP levels were
      markedly elevated in patients with CHRF (n=60; geometric mean (SD) 546.4 (4.9)
      pg/mL; p<0.001) compared to healthy controls (n=182; 49.0 (2.2) pg/mL). After
      excluding patients with concomitant HF or renal impairment, levels were still
      increased (n=43; 393.2 (3.8) pg/mL; p<0.001). According to multivariate
      regression, hypoxia and exacerbation independently determined NT-proBNP levels
      (p<0.05 each). After initiation of NIV, blood gases and lung function improved
      and NT-proBNP decreased (-31.3 (0.3)%; p<0.001). During 22.5 (2.2) months follow
      up, NT-proBNP was not significantly associated with survival in the total
      population, however, the subgroup of patients with levels >722 pg/mL (67th
      percentile) and no adherence to NIV displayed poor prognosis (hazard ratio=0.21;
      95%-CI=0.022-0.580; p=0.0091). CONCLUSIONS: NT-proBNP was highly elevated in
      patients with CHRF and correlated with the degree of respiratory impairment and
      exacerbation. Correspondingly, treatment including NIV led to reduction of NT
      proBNP. These data indicate a potential role of NT-proBNP in assessing disease
      severity, treatment efficacy and prognosis in CHRF.

PMID- 17532201
TI  - Polymorphisms of STAT-6, STAT-4 and IFN-gamma genes and the risk of asthma in
      Chinese population.
AB  - BACKGROUND: Asthma is a complex disease resulting from multiple gene-gene and
      gene-environment interactions. Study on gene-gene interactions could provide
      insight into the pathophysiologic mechanisms of the disease. OBJECTIVES: We
      investigated the single nucleotide polymorphisms and interactions among three
      different loci in three candidate genes (STAT-6 G2964A, STAT-4 T90089C and IFN
      gamma T874A) in 95 Chinese asthmatic subjects and 95 matched controls to
      determine the possible associations with asthma. METHODS: Genotyping of the gene
      polymorphisms was performed by means of PCR-SSCP analysis. Genotype-phenotype
      associations were examined in dominant and recessive genetic models using
      logistic regression. The method of multifactor dimensionality reduction was used
      to analyze gene-gene interactions. RESULTS: No statistically significant
      difference was found in the distribution of the STAT-6 G2964A polymorphisms
      between asthmatic patients and controls in this case-control study. The STAT-4
      T90089C polymorphisms were significantly associated with asthma in the dominant
      model (p=0.007). As for the IFN-gamma T874A, the significant associations were
      found in both dominant model (p=0.004) and recessive model (p=0.006). A
      significant gene-gene interaction was found among STAT-6, STAT-4 and IFN-gamma on
      the risk of asthma. In the best 3-locus model, the odds ratio for the high-risk
      to the low-risk group was 6.9 (95% CI, 3.5-13.7; p<0.0001). CONCLUSIONS: Our
      findings suggest that STAT-4 T90089C and IFN-gamma T874A polymorphisms might be
      the genetic factors for the risk of asthma in the Chinese population. In
      addition, the significant interactions among STAT-6 G2964A, STAT-4 T90089C and
      IFN-gamma T874A may increase an individual's susceptibility and contribute to the
      pathogenesis of asthma.

PMID- 17532203
TI  - Biosensing environmental pollution.
AB  - Whole-cell biosensors are finding increasing use for the detection of
      environmental pollution and toxicity. These biosensors are constructed through
      the fusion of promoters, responsive to the relevant environmental conditions, to
      easily monitored reporter genes. Depending on the choice of reporter gene,
      expression can be monitored by the production of colour, light, fluorescence or
      electrochemical reactions. Recent advances in this area have included the
      development of biosensors of compact size that enable the on-line and in situ
      monitoring of a large number of environmental parameters.

PMID- 17532205
TI  - Anaerobic fermentation of glycerol: a path to economic viability for the biofuels
      industry.
AB  - Although biofuels such as biodiesel and bioethanol represent a secure, renewable
      and environmentally safe alternative to fossil fuels, their economic viability is
      a major concern. The implementation of biorefineries that co-produce higher value
      products along with biofuels has been proposed as a solution to this problem. The
      biorefinery model would be especially advantageous if the conversion of
      byproducts or waste streams generated during biofuel production were considered.
      Glycerol-rich streams generated in large amounts by the biofuels industry,
      especially during the production of biodiesel, present an excellent opportunity
      to establish biorefineries. Once considered a valuable 'co-product', crude
      glycerol is rapidly becoming a 'waste product' with a disposal cost attributed to
      it. Given the highly reduced nature of carbon in glycerol and the cost advantage
      of anaerobic processes, fermentative metabolism of glycerol is of special
      interest. This review covers the anaerobic fermentation of glycerol in microbes
      and the harnessing of this metabolic process to convert abundant and low-priced
      glycerol streams into higher value products, thus creating a path to viability
      for the biofuels industry. Special attention is given to products whose synthesis
      from glycerol would be advantageous when compared with their production from
      common sugars.

PMID- 17532206
TI  - Cutaneous melanoma in the Maltese Islands: 2000-2004.
AB  - This study aimed to, prospectively, over the 5-year period 2000-2004, accurately
      determine features of cutaneous melanoma in the Maltese Islands. Data from
      clinicians were supplemented by histology reports, and where necessary, histology
      slides were reviewed. Information collected included demographic details
      including age and gender, anatomical site, Clark's level, Breslow thickness and
      clinico-pathological melanoma type. During the study period the age-standardised
      (European Standard Population) rates for invasive melanoma were 8.81 per 100,000
      (males) and 7.29 per 100,000 (females) and increased with age. By the end of the
      study, information on 166 cases of primary invasive cutaneous malignant melanoma
      were collected. The commonest site affected in males was the trunk (54%) and in
      females the lower limbs (41%). Overall, 33.8% of invasive melanomas had a Breslow
      thickness >1.5mm. The initial melanoma excision was performed by a dermatologist
      in 68.2% and plastic surgeon in 20.8%. More cases presented in late spring and
      summer, particularly in females. Melanoma incidence in Malta is lower than that
      in high-incidence countries and northern Europe and is similar to that in
      southern Europe. However, incidence appears to be increasing and a relatively
      high proportion of patients present with thick lesions emphasising the importance
      of continued efforts to diagnose cases earlier.

PMID- 17532207
TI  - Humoral immune responses to MUC1 in women with a BRCA1 or BRCA2 mutation.
AB  - INTRODUCTION: Breast cancer patients with early disease and a natural humoral
      response to MUC1 have a favourable prognosis, suggesting a possible role of MUC1
      antibodies (ab) in controlling haematogenous tumour dissemination and outgrowth.
      The aim of the study was to evaluate humoral immune responses to MUC1 in women at
      hereditary high risk of breast cancer to investigate whether this immune response
      could play a role in the prevention of disease. MATERIALS AND METHODS: CA15.3
      (U/mL), and IgG and IgM ab to MUC1 (arbitrary units per mL, Arb-U/mL) were
      measured in serum samples obtained from 422 women at hereditary high risk of
      breast/ovarian cancer, of whom 127 BRCA1/2 carriers, attending the Familial
      Cancer Clinic of the VU University Medical Centre, and from 370 age-matched
      healthy controls. Serum samples obtained from women who developed breast cancer
      (N=12) or breast cancer recurrence (N=17), and from women who underwent
      prophylactic mastectomy (N=12) and had no breast lesions were also tested.
      RESULTS: CA15.3 ranked significantly higher in mutation carriers than in controls
      (P=0.03). MUC1 IgG ab levels ranked significantly lower in BRCA1/2 mutation
      carriers than in controls (P=0.003). MUC1 IgG levels were not significantly
      different (P=0.53) between women who developed primary breast cancer (median
      0.72Arb-U/ml, range 0.52-2.44Arb-U/ml) and women who underwent prophylactic
      mastectomy and had no breast lesions (median 1.04Arb-U/ml, range 0.43-2.88Arb
      U/ml). CONCLUSION: Serum levels of natural IgG ab to MUC1 are lower in BRCA1/2
      mutation carriers than in healthy controls. Furthermore, in contrast to previous
      results in women with sporadic breast cancer, no elevated MUC1 IgG ab were seen
      in women at hereditary high risk who developed breast cancer. Prophylactic
      immunotherapy with MUC1 substrates may be a strategy to reduce the risk of breast
      cancer in BRCA1/2 mutation carriers, strengthening tumour immune surveillance.

PMID- 17532208
TI  - Surgical options in the management of advanced and recurrent colorectal cancer.

PMID- 17532209
TI  - Potential of constructed wetlands in treating the eutrophic water: evidence from
      Taihu Lake of China.
AB  - Three parallel units of pilot-scale constructed wetlands (CWs), i.e., vertical
      subsurface flow (VSF), horizontal subsurface flow (HSF) and free water surface
      flow (FWS) wetland were experimented to assess their capabilities in purifying
      eutrophic water of Taihu Lake, China. Lake water was continuously pumped into the
      CWs at a hydraulic loading rate of 0.64 m d(-1) for each treatment. One year's
      performance displayed that average removal rates of chemical oxygen demand (COD),
      ammonia nitrogen (NH(4)(+)-N), nitrate nitrogen (NO(3)(-)-N), total nitrogen (TN)
      and total phosphorous (TP) were 17-40%, 23-46%, 34-65%, 20-52% and 35-66%,
      respectively. The VSF and HSF showed statistically similar high potential for
      nutrients removal except NH(4)(+)-N, with the former being 14% higher than that
      of the latter. However, the FWS wetland showed the least effect compared to the
      VSF and HSF at the high hydraulic loading rate. Mean effluent TP concentrations
      in VSF (0.056 mg L(-1)) and HSF (0.052 mg L(-1)) nearly reached Grade III (0.05
      mg L(-1) for lakes and reserviors) water quality standard of China. Wetland
      plants (Typha angustifolia) grew well in the three CWs. We noted that plant
      uptake and storage were both important factors responsible for nitrogen and
      phosphorous removal in the three CWs. However, harvesting of the above ground
      biomass contributed 20% N and 57% P of the total N and P removed in FWS wetland,
      whereas it accounted for only 5% and 7% N, and 14% and 17% P of the total N and P
      removed in VSF and HSF CWs, respectively. Our findings suggest that the
      constructed wetlands could well treat the eutrophic lake waters in Taihu. If land
      limiting is considered, VSF and HSF are more appropriate than FWS under higher
      hydraulic loading rate.

PMID- 17532210
TI  - Electricity generation using a baffled microbial fuel cell convenient for
      stacking.
AB  - To make sure that microbial fuel cells (MFCs) are more convenient to stack, a
      baffled single-chambered MFC with two groups of electrodes sharing only one anode
      chamber was designed and the performance was examined. The experiments showed
      that the prototype MFC generated electrical power (maximum of 133 mW/m(2)) while
      removing up to 88% of chemical oxygen demand (COD) in 91 h. Volumetric power
      increased as electrode area per anode compartment volume increased, indicating
      that the MFC with two groups of electrodes was better than that with one group.
      Power density as a function of wastewater concentration was modeled according to
      saturation kinetics, with a maximum power density of P(max)=164 mW/m(2) (fixed
      100 Omega resistor) and half-saturation concentration of K(s)=259 mg/l. The
      hydraulic retention time (HRT) was examined as a factor influencing the power
      generation. When it was 15.5h, the voltage and the power density reached the
      maximum 0.413 V and 108 mW/m(2).

PMID- 17532211
TI  - Fed-batch cultivation of Wautersia eutropha.
AB  - Batch kinetics of polyhydroxybutyrate (PHB) synthesis in a bioreactor under
      controlled conditions of pH and dissolved oxygen gave a biomass of 14 g l(-1)
      with a PHB concentration of 6.1 g l(-1) in 60 h. The data of the batch kinetics
      was used to develop a mathematical model, which was then extrapolated to fed
      batch by incorporating the dilution due to substrate feeding. Offline computer
      simulation of the fed-batch model was done to develop the nutrient feeding
      strategies in the fed-batch cultivation. Fed-batch strategies with constant
      feeding of only nitrogen and constant feeding of both nitrogen and fructose were
      tried. Constant feeding strategy for nitrogen and fructose gave a better PHB
      production rate of 0.56 g h(-1) over the value obtained in batch cultivation (PHB
      production rate - 0.4 g h(-1)).

PMID- 17532212
TI  - Quantitative comparison of stability of ANAMMOX process in different reactor
      configurations.
AB  - A new stability evaluating system for ANAMMOX comprising three instability
      indices i.e. coefficient of variation ratio, coefficient of range ratio and
      coefficient of regression function derivative was established. Three lab-scale
      ANAMMOX reactors viz upflow anaerobic sludge blanket (UASB) reactor, upflow
      stationary fixed film (USFF) reactor and anaerobic sequencing batch reactor
      (ASBR) were compared for their stability based on the established criterion
      against the hydraulic and substrate concentration shocks. The results showed that
      all ANAMMOX reactors under investigation were more tolerant to the hydraulic
      shock than substrate concentration shock. The UASB reactor was the most stable
      reactor configuration towards substrate concentration shock, followed by the USFF
      reactor and ASBR. However, the ASBR proved the most tolerant to hydraulic shock,
      followed by the UASB reactor and USFF reactor. In terms of stability, UASB
      reactor was more suitable configuration compared with USFF reactor. The
      instability indices proved to be effective and explicit for the evaluation of
      ANAMMOX systems.

PMID- 17532213
TI  - Mechanical mode floating medium filters for recirculating systems in aquaculture
      for higher solids retention and lower freshwater usage.
AB  - The aim of this work was to develop a better understanding of a floating medium
      in a mechanical filtration mode. The experiments were carried out using a
      commonly available polystyrene floating medium filter with the grain size of 1mm.
      A sand medium filter with the similar grain size was also tested for the
      comparison. A short-term trial of 2h and a long-term of 20 days filtration times
      were conducted with three custom manufactured pressurized filters of 16l. The
      filters were operated under three different configurations: (i) upflow with
      floating media (UFMF), (ii) downflow with floating media (DFMF) and (iii)
      downflow with a sand medium (DSF). The results of the long-term trial indicated
      that at a flow rate of 22 m/h, the UFMF and DSF had similar solid removal
      capacity with an average total suspended solids (TSS) removal efficiency of 60%.
      The DFMF could only remove 33% of TSS. However, during the short-term trial, TSS
      removal efficiency of the UFMF was better compared to the DSF (e.g., 71%, 56% and
      57% of TSS removal in UFMF compared to 66%, 49% and 41% in the DSFF at the flow
      rates of 20, 25 and 31m/h, respectively). The energy requirements of each filter
      were compared by measuring the pressure differential across each filter. The long
      term trial indicated that the UFMF had a significantly less pressure differential
      (44 kPa) compared to the DSF (80 kPa) (p<0.001). This was further confirmed that
      at different flow rates whereby the DSF displayed higher pressure differentials
      for filtration rates at 350, 450, 550 and 800 l/h. The study indicated that
      floating medium filter was better and more applicable to recirculating
      aquaculture systems than conventional pressurized sand filter.

PMID- 17532214
TI  - C-8 Modifications of 3-alkyl-1,8-dibenzylxanthines as inhibitors of human
      cytosolic phosphoenolpyruvate carboxykinase.
AB  - New modifications on the C-8 4-aminobenzyl unit of the previously reported 3
      alkyl-1,8-dibenzylxanthine inhibitors of cPEPCK are presented. The most active
      compound reported here is the 5-chloro-1,3-dimethyl-1H-pyrazole-4-sulfonic acid
      amide derivative 2 with an IC(50) of 0.29+/-0.08 microM. An X-ray analysis of a
      heteroaromatic sulfonamide is presented showing a new pi-pi interaction.

PMID- 17532215
TI  - Discovery of cyclopentane- and cyclohexane-trans-1,3-diamines as potent melanin
      concentrating hormone receptor 1 antagonists.
AB  - We herein report the optimization of cyclopentane- and cyclohexane-1,3-diamine
      derivatives as novel and potent MCH-R1 antagonists. Structural modifications of
      the 2-amino-quinoline and thiophene moieties found in the initial lead compound
      served to improve its metabolic stability profile and MCH-R1 affinity, and
      revealed unprecedented SAR when compared to other 2-amino-quinoline-containing
      MCH-R1 antagonists.

PMID- 17532216
TI  - Rapid hit to lead evaluation of pyrazolo[3,4-d]pyrimidin-4-one as selective and
      orally bioavailable mGluR1 antagonists.
AB  - Our HTS effort yielded a preferential mGluR1 pyrimidinone antagonist 1 with lead
      like characteristics. Rapid hit to lead (HTL) study identified compounds with
      improved functional activity and selectivity such as 1b with little improvements
      in ADME properties. Addition of an aminosulfonyl group on the N-1 aromatic ring
      led to 2f, a compound with similar in vitro biochemical profiles as those of 1b
      but drastically improved in vitro ADME properties. These improvements were
      paralleled by rat PK study characterized by low clearance and quantitative
      bioavailability. Compound 2f represented a true lead-like molecule that is
      amenable for further lead optimization (LO) evaluation.

PMID- 17532217
TI  - Video-assisted axillary surgery for cancer: non-randomized comparison with
      conventional techniques.
AB  - Endoscopic techniques have been introduced in most of surgical disciplines
      including surgery for breast cancer. However, there is shortage of evidence-based
      guidelines and oncological outcome data. We present a controlled trial of
      endoscopic axillary surgery for breast cancer with mid-term oncologic results.
      Fifty cases of axilloscopy for sentinel node biopsy, axillary sampling or full
      axillary dissection were included. Sentinel node biopsy was accomplished with the
      blue dye technique. Full axillary dissection was performed with a three-port
      approach with gas insufflation without liposuction. Endoscopic axillary
      dissection significantly lowered duration of drainage and operative blood loss.
      Lymph node harvest with endoscopic approach was significantly lower than with
      open procedure. One case developed axillary recurrence. Endoscopic sentinel node
      biopsy yielded identification rate of 80%. Current data do not justify the
      oncological safety of resectional endoscopic procedures. Endoscopically assisted
      axillary cancer surgery is technically feasible. The technique is valuable to
      maximize utility of blue dye method for sentinel lymphadenectomy in areas with no
      access to radio-guided surgery.

PMID- 17532218
TI  - Skin movement errors in measurement of sagittal lumbar and hip angles in young
      and elderly subjects.
AB  - Errors in measurement of sagittal lumbar and hip angles due to skin movement on
      the pelvis and/or lateral thigh were measured in young (n = 21, age = 18.6 +/-
      2.1 years) and older (n = 23, age = 70.9 +/- 6.4 years) age groups. Skin
      reference markers were attached over specific landmarks of healthy young and
      elderly subjects, who were videotaped in three static positions of hip flexion
      using the 2D PEAK Motus video analysis system. Sagittal lumbar and hip angles
      were calculated from skin reference markers and manually palpated landmarks. The
      elderly subjects demonstrated greater errors in lumbar angle due to skin movement
      on the pelvis only in the maximal hip flexion position. The traditional model
      (ASIS-PSIS-GT-LFE) underestimated sagittal hip angle and the revised model (ASIS
      PSIS-2/3Th-1/4Th) provided more accurate measurement of sagittal hip angle
      throughout the full available range of hip flexion. Skin movement on the pelvis
      had a small counterbalancing effect on the larger errors from lateral thigh
      markers (GT-LFE), thereby decreasing hip angle error.

PMID- 17532219
TI  - Pial and arachnoid welding for restoration of normal cord anatomy after excision
      of intramedullary spinal cord tumors.
AB  - A significant postoperative problem in patients undergoing excision of
      intramedullary tumors is painful dysesthesiae, attributed to various causes,
      including edema, arachnoid scarring and cord tethering. The authors describe a
      technique of welding the pia and arachnoid after the excision of intramedullary
      spinal cord tumors used in seven cases. Using a fine bipolar forcep and a low
      current, the pial edges of the myelotomy were brought together and welded under
      saline irrigation. A similar method was used for closing the arachnoid while the
      dura was closed with a running 5-0 vicryl suture. Closing the pia and arachnoid
      restores normal cord anatomy after tumor excision and may reduce the incidence of
      postoperative painful dysesthesiae.

PMID- 17532220
TI  - Schwannoma with tentorial attachment in the cerebellopontine angle mimicking a
      meningioma.
AB  - Intracranial schwannoma not associated with the cranial nerves is rare. It is
      also an intriguing neoplasm since the Schwann cell is not native to the central
      nervous system. To date only four cases of intracranial schwannoma arising from
      the tentorium have been reported. We present a 49-year-old woman who harboured a
      schwannoma with a tentorial attachment in the right cerebellopontine angle and
      describe the relevant clinical, radiological and pathological findings. In
      addition, we briefly review the main hypotheses for the origin of this neoplasm
      and highlight its resemblance to meningioma and inclusion as a differential
      diagnosis.

PMID- 17532221
TI  - The 1,4-naphthoquinone scaffold in the design of cysteine protease inhibitors.
AB  - A series of 1,4-naphthoquinone derivatives diversely substituted at C-2, C-3, C-5
      and C-8, prepared by reaction of amines, amino acids and alcohols with commercial
      1,4-naphthoquinones, has been evaluated against papain and bovine spleen
      cathepsin B. These 1,4-naphthoquinone derivatives were found to be irreversible
      inhibitors for both cysteine proteases, with second-order rate constants, k(2),
      ranging from 0.67 to 35.4M(-1)s(-1) for papain, and from 0.54 to 8.03M(-1)s(-1)
      for cathepsin B. Some derivatives display a hyperbolic dependence of the first
      order inactivation rate constant, k(obs), with the inhibitor concentration,
      indicative of a specific interaction process between enzyme and inhibitor. The
      chemical reactivity of the compounds towards cysteine as a model thiol is
      dependent on the naphthoquinone LUMO energy, whereas papain inactivation is not.
      The 1,4-naphthoquinone derivatives are inactive against the serine protease,
      porcine pancreatic elastase.

PMID- 17532222
TI  - Adsorption behavior of some radionuclides on the Chinese weathered coal.
AB  - The equilibrium and kinetic properties of Am(III), Eu(III) and Cs(I) ions
      adsorption by three weathered coals (WCs) from China, have been investigated in
      batch stirred-tank experiments. The effects of contact time, solution acidity and
      initial sorbate concentration on the adsorption of Am(III), Eu(III) and Cs(I) by
      Yuxian(YX) Tongchuan (TC) and Pingxiang (PX) WC were evaluated. The radionuclide
      ions are able to form complex compounds with carboxylic and phenolic groups of
      WCs and they are also bounded with phenolic groups even at high acidity reaction
      solution (>0.1 mol/L). Mechanisms including ion exchange, complexation and
      adsorption to the coal surface are possible in the sorption process. The acidity
      of the solution played an important role in the adsorption. Even acidity as high
      as 0.1 mol/L, 60% of Am(III) or Eu(III), 40% of Cs(I) were found to be sorbed on
      the YX WC, which had the best adsorption capacity for Am(III) and Eu(III). Our
      batch adsorption studies showed the equilibrium adsorption data fit the linear
      Langmuir and Freundlich adsorption isotherm. The maximum equilibrium uptake of
      Eu(III) were 0.412, 3.701, 5.446 mmol/g for JXWC, TCWC and YXWC, respectively.

PMID- 17532223
TI  - Production of Ac-225 for cancer therapy by photon-induced transmutation of Ra
      226.
AB  - The increasing application of Ac-225 for cancer therapy indicates the potential
      need for its increased production and availability. The production of Ac-225 has
      been achieved using bremsstrahlung photons from an 18 MV medical linear
      accelerator (linac) to bombard a Ra-226 target. A linac dose of 2800 Gy produced
      about 64 microCi of Ra-225, which decays to Ac-225. This result, while consistent
      with the theoretical calculations, is far too low to be of practical use. A more
      powerful linac is required that runs at a higher current, longer pulse length and
      higher frequency for practical production. This process could also lead to the
      reduction of the nuclear waste product Ra-226.

PMID- 17532224
TI  - Differential cytokine and chemokine responses of bovine mammary epithelial cells
      to Staphylococcus aureus and Escherichia coli.
AB  - We studied the inflammatory and immune responses of bovine mammary epithelial
      cells (bMEC) infected by mastitis isolates of Staphylococcus aureus. Primary
      cultures of bMEC were co-incubated separately with three strains of S. aureus and
      one strain of Escherichia coli. Transcriptional levels and/or protein release of
      interleukin-8 (IL-8), growth related oncogene alpha (GRO-alpha), growth related
      oncogene beta (GRO-beta), tumor necrosis factor alpha (TNF-alpha), interleukin
      1beta (IL-1beta), transforming growth factor beta1 (TGF-beta1) and interleukin-10
      (IL-10) were measured at 3, 10 and 24h post-infection (PI). The results indicated
      that at earlier hours of co-culture, bMEC infected with S. aureus or E. coli
      expressed more IL-1beta, TNF-alpha, IL-8 and GRO-alpha mRNA than uninfected bMEC.
      Furthermore, infected bMEC released more TNF-alpha, IL-8, GRO-alpha and GRO-beta
      proteins than uninfected bMEC. However, differential transcription and release of
      some cytokines/chemokines from bMEC was observed according to the strain of S.
      aureus and bacteria Gram type. In conclusion, bMEC did not show an anti
      inflammatory potential through IL-10 or TGF-beta1 release. Nevertheless, bMEC
      were able to release neutrophil-mobilizing chemokines and pro-inflammatory
      cytokines upon bacterial stimulation, strongly suggesting that bMEC are active
      contributors to immune and inflammatory responses of mammary gland. In addition,
      the clinical characteristics and resolution of mastitis may be partly determined
      by the responses of bMEC according to S. aureus strains and bacteria Gram type.

PMID- 17532225
TI  - Novel software for the assignment of peaks from tandem mass spectrometry spectra
      of synthetic polymers.
AB  - Novel software has been developed to aid the interpretation of tandem mass
      spectrometry (MS/MS) data from synthetic polymers. The software is particularly
      focused toward aiding the end-group determination of these materials by
      significantly speeding up the interpretation process. This allows information on
      the initiator and/or chain transfer agents, used to generate the polymer, and the
      mechanism of termination to be inferred from the data much more rapidly. The
      software allows the validity of hypothesized structures to be rapidly tested by
      automatically annotating the data file using previously proposed fragmentation
      rules for synthetic polymers. Low-energy collision-induced dissociation (CID)
      data from methacrylate, styrene, and polyether oligomers are used as example data
      for the software. Exact-mass CID information was used to aid the understanding of
      the dissociation mechanism of the polymers. The software can use exact-mass data
      to provide more confidence in the results. The MS/MS results indicate that the
      fragmentation pathways are those previously proposed for these polymers.

PMID- 17532226
TI  - Rapid resolution of carbohydrate isomers by electrospray ionization ambient
      pressure ion mobility spectrometry-time-of-flight mass spectrometry (ESI-APIMS
      TOFMS).
AB  - Carbohydrates are an extremely complex group of isomeric molecules that have been
      difficult to analyze in the gas phase by mass spectrometry because (1) precursor
      ions and product ions to successive stages of MS(n) are frequently mixtures of
      isomers, and (2) detailed information about the anomeric configuration and
      location of specific stereochemical variants of monosaccharides within larger
      molecules has not been possible to obtain in a general way. Herein, it is
      demonstrated that gas-phase analyses by direct combination of electrospray
      ionization, ambient pressure ion mobility spectrometry, and time-of-flight mass
      spectrometry (ESI-APIMS-TOFMS) provides sufficient resolution to separate
      different anomeric methyl glycosides and to separate different stereoisomeric
      methyl glycosides having the same anomeric configuration. Reducing sugars were
      typically resolved into more than one peak, which might represent separation of
      cyclic species having different anomeric configurations and/or ring forms. The
      extent of separation, both with methyl glycosides and reducing sugars, was
      significantly affected by the nature of the drift gas and by the nature of an
      adducting metal ion or ion complex. The study demonstrated that ESI-APIMS-TOFMS
      is a rapid and effective analytical technique for the separation of isomeric
      methyl glycosides and simple sugars, and can be used to differentiate glycosides
      having different anomeric configurations.

PMID- 17532227
TI  - The nucleoprotein of Tomato spotted wilt virus as protein tag for easy
      purification and enhanced production of recombinant proteins in plants.
AB  - Upon infection, Tomato spotted wilt virus (TSWV) forms ribonucleoprotein
      particles (RNPs) that consist of nucleoprotein (N) and viral RNA. These
      aggregates result from the homopolymerization of the N protein, and are highly
      stable in plant cells. These properties feature the N protein as a potentially
      useful protein fusion partner. To evaluate this potential, the N protein was
      fused to the Aequorea victoria green fluorescent protein (GFP), either at the
      amino or carboxy terminus, and expressed in plants from binary vectors in
      Nicotiana benthamiana leaves were infiltrated with Agrobacterium tumefaciens and
      evaluated after 4 days, revealing an intense GFP fluorescence under UV light.
      Microscopic analysis revealed that upon expression of the GFP:N fusion a small
      number of large aggregates were formed, whereas N:GFP expression led to a large
      number of smaller aggregates scattered throughout the cytoplasm. A simple
      purification method was tested, based on centrifugation and filtration, yielding
      a gross extract that contained large amounts of N:GFP aggregates, as confirmed by
      GFP fluorescence and Western blot analysis. These results show that the
      homopolymerization properties of the N protein can be used as a fast and simple
      way to purify large amounts of proteins from plants.

PMID- 17532228
TI  - A novel supervised trajectory segmentation algorithm identifies distinct types of
      human adenovirus motion in host cells.
AB  - Biological trajectories can be characterized by transient patterns that may
      provide insight into the interactions of the moving object with its immediate
      environment. The accurate and automated identification of trajectory motifs is
      important for the understanding of the underlying mechanisms. In this work, we
      develop a novel trajectory segmentation algorithm based on supervised support
      vector classification. The algorithm is validated on synthetic data and applied
      to the identification of trajectory fingerprints of fluorescently tagged human
      adenovirus particles in live cells. In virus trajectories on the cell surface,
      periods of confined motion, slow drift, and fast drift are efficiently detected.
      Additionally, directed motion is found for viruses in the cytoplasm. The
      algorithm enables the linking of microscopic observations to molecular phenomena
      that are critical in many biological processes, including infectious pathogen
      entry and signal transduction.

PMID- 17532229
TI  - Anaesthetic use in animal models for neuroimaging.

PMID- 17532230
TI  - The advantage of combining MEG and EEG: comparison to fMRI in focally stimulated
      visual cortex.
AB  - To exploit the high (millisecond) temporal resolution of magnetoencephalography
      (MEG) and electroencephalography (EEG) for measuring neuronal dynamics within
      well-defined brain regions, it is important to quantitatively assess their
      localizing ability. Previous modeling studies and empirical data suggest that a
      combination of MEG and EEG signals should yield the most accurate localization,
      due to their complementary sensitivities. However, these two modalities have
      rarely been explicitly combined for source estimation in studies of recorded
      brain activity, and a quantitative empirical assessment of their abilities,
      combined and separate, is currently lacking. Here we studied early visual
      responses to focal Gabor patches flashed during subject fixation. MEG and EEG
      data were collected simultaneously and were compared with the functional MRI
      (fMRI) localization produced by identical stimuli in the same subjects. This
      allowed direct evaluation of the localization accuracy of separate and combined
      MEG/EEG inverse solutions. We found that the localization accuracy of the
      combined MEG+EEG solution was consistently better than that of either modality
      alone, using three different source estimation approaches. Further analysis
      suggests that this improved localization is due to the different properties of
      the two imaging modalities rather than simply due to increased total channel
      number. Thus, combining MEG and EEG data is important for high-resolution
      spatiotemporal studies of the human brain.

PMID- 17532231
TI  - The contribution of 18F-FDG PET in preoperative epilepsy surgery evaluation for
      patients with temporal lobe epilepsy A meta-analysis.
AB  - OBJECTIVE: To assess the predictive diagnostic added value of positron emission
      tomography (PET) in preoperative epilepsy surgery evaluation for patients with
      temporal lobe epilepsy (TLE). METHODS: A meta-analysis of publications from 1992
      to 2006 was performed. Forty-six studies were identified that met inclusion
      criteria presenting detailed diagnostic test results and a classified
      postoperative outcome. Studies exclusively reporting on patients with brain
      tumors or on children were excluded. RESULTS: The analyses were complicated by
      significant differences in study design and often by lack of precise patient
      data. Ipsilateral PET hypometabolism showed a predictive value of 86% for good
      outcome. The predictive value was 80% in patients with normal MRI and 72% in
      patients with non-localized ictal scalp EEG. In a selected population of 153 TLE
      patients with a follow-up of >12 months PET correlated well with other non
      invasive diagnostic tests, but none of the odds ratios of any test combination
      was significant. CONCLUSION: Our data confirm that ipsilateral PET hypometabolism
      may be an indicator for good postoperative outcome in presurgical evaluation of
      drug-resistant TLE, although the actual diagnostic added value remained
      questionable and unclear. PET does not appear to add value in patients localized
      by ictal scalp EEG and MRI. Prospective studies limited to non-localized ictal
      scalp EEG or MRI-negative patients are required for validation.

PMID- 17532232
TI  - Potential influence of IL1B haplotype and IL1A-IL1B-IL1RN extended haplotype on
      hand osteoarthritis risk.
AB  - OBJECTIVE: To assess osteoarthritis (OA) association with the human interleukin-1
      (IL-1) region. DESIGN: Sixty-four European-descent cases with radiographic hand
      OA and 48 European-descent controls were genotyped at nine single nucleotide
      polymorphism (SNP), one variable-number-of-tandem-repeat (VNTR), and one
      microsatellite marker extending across loci for IL-1alpha (IL1A), IL-1beta
      (IL1B), and IL-1 receptor antagonist (IL1RN). The genotype data were used to
      reconstruct individual locus haplotypes, and then locus haplotypes were used as
      superalleles for extended haplotype reconstruction. RESULTS: Nine different
      extended IL1A-IL1B-IL1RN haplotypes occurred at a frequency 0.05 or greater in
      either cases or controls. Only two IL1A-IL1B-IL1RN extended haplotypes were
      consistent with previously described extended risk haplotypes and totaled n=9 in
      cases and n=3 in controls [odds ratio (OR) 2.1, Haldane's chi(2) 1.67, one-sided
      P 0.1]. Our prior report showed hand OA association with homozygous IL1B
      rs1143633 minor allele genotype. All except one extended risk haplotype copy also
      had the IL1B rs1143633 minor allele. The rs1143633 genotype association was
      explained by one common six-SNP IL1B haplotype bearing rs1143633 minor allele and
      also risk alleles at rs1143634, rs1143627, and rs16944, component markers of the
      previously described extended risk haplotypes. The IL1B haplotype bearing all
      three risk alleles was found in 16 haplotype-homozygous hand OA cases and in four
      haplotype-homozygous controls and conferred OR 3.4 among homozygotes (nominal P
      value 0.006). CONCLUSION: Our evidence broadly supports the genetic association
      of OA phenotypes with an IL-1 region extended risk haplotype and specifically
      IL1B genotype. The extended risk haplotype previously associated with hip OA
      appears to be less frequent and has weaker genetic effect in hand OA. Hand OA
      risk is conferred by homozygous state for the IL1B haplotype characteristic of
      the extended risk haplotype.

PMID- 17532233
TI  - NF-kappaB responds to mechanical strains in osteoblast-like cells, and lighter
      strains create an NF-kappaB response more readily.
AB  - This study was to examine the early responses of nuclear factor kappa B (NF
      kappaB) to mechanical strains in MG-63. MG-63 cells were subjected to cyclic
      uniaxial compressive or tensile strain, produced by a four-point bending system,
      at 1000 microstrain or 4000 microstrain for 5 min, 15 min, 30 min and 1h,
      respectively. Control cells received the same treatment with no mechanical stress
      loading. Expression of NF-kappaB (p60) was measured by Western blotting. NF
      kappaB responded rapidly to mechanical stimuli in MG-63 cells. NF-kappaB was
      activated by cyclic uniaxial stretch at 1000 microstrain while it was restrained
      under a compressive strain environment at 1000 microstrain (P<0.001). The effects
      reversed for tension and compression at 4000 microstrain (P<0.001). Furthermore,
      strains at 1000 microstrain affected NF-kappaB expression much easier than those
      at 4000 microstrain. This indicates that there may be different responding
      mechanisms or mechanotransduction pathways for different mechanical stimuli.

PMID- 17532234
TI  - Isolation and characterization of EG-like cells from Chinese swamp buffalo
      (Bubalus bubalis).
AB  - There have been few studies done on the isolation and characterization of Chinese
      swamp buffalo embryonic germ cells (EG cells). Here, we first report on EG-like
      cells isolated from Chinese swamp buffalo fetuses. The results showed the cells
      grew in large, multilayered colonies, which were densely packed with an obvious
      border resembling mouse embryonic stem cells (ES cells) and EG cells. The buffalo
      EG-like cells expressed AP, SSEA-1, SSEA-3, SSEA-4 and OCT-4. By RT-PCR, we found
      that undifferentiated swamp buffalo EG-like cells expressed the OCT-4, NANOG,
      SOX2, FOXD3, GP130, STAT3, and HEB gene mRNA, but not Fgf4. When these cells were
      cultured for more than 2weeks without passage, they could differentiate into
      several types of cells including fibroblast-like, neuron-like, smooth muscle
      like, and epithelial-like cells. Some cells formed simple embryoid bodies (EBs)
      and cystic EBs by suspension culture. By RT-PCR, we found cystic EBs expressed
      FOXD3, GP130, STAT3 and HEB gene mRNA, but not OCT-4, NANOG, and SOX2 gene mRNA,
      which could be detected in undifferentiated buffalo EG-like cells. At the same
      time, the expression of KERATIN-14 (Endoderm), GATA4, ACTA2 (Mesoderm) and TUBB3
      (Ectoderm) gene mRNA were also detected in cystic EBs. The results suggested that
      these cells were capable of forming three germ layers in in vitro
      differentiation. The expression of OCT-4, NANOG and SOX2 might be essential for
      Chinese swamp buffalo EG-like cells in a pluripotent state. During the isolation
      and culture of Chinese swamp buffalo EG-like cells, we found the fetuses that
      were at 30-80days post-coitus were more efficient than others; and the mechanical
      method was better than trypsin digestion. The maximal passage of the mechanical
      method was eight, but the trypsin digestion was just three passages. So it seemed
      like that the buffalo EG-like cells were sensitive to trypsin. In summary, we
      were the first to isolate and characterize Chinese swamp buffalo EG-like cells
      that had morphology and characterization similar to those of established EG/EG
      like cells in mouse and human.

PMID- 17532235
TI  - WITHDRAWN: Jolkinolide B-induced mitochondria-dependent apoptosis in K562 cells.
AB  - This article has been withdrawn consistent with Elsevier Policy on Article
      Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). The Publisher
      apologizes for any inconvenience this may cause.

PMID- 17532236
TI  - Integrating molecular information into treatment of childhood acute lymphoblastic
      leukemia--a perspective from the BFM Study Group.
AB  - Acute lymphoblastic leukemia (ALL) is the most common malignancy of childhood and
      is treated with chemotherapy alone or, in particular subgroups, with additional
      radiation therapy and/or stem cell transplantation. The treatment intensity is
      adjusted according to prognostic factors associated with the risk of ALL
      recurrence. On Berlin-Frankfurt-Munster (BFM) protocols, the widely applicable
      early in vivo response to treatment as measured by the reduction of leukemic
      cells in the blood or bone marrow is currently the most important prognostic
      factor. However, although overall long-term cure rates for childhood ALL treated
      on risk-adapted protocols have dramatically improved over the last decades and,
      to date, are higher than 75%, a significant number of patients still die due to
      recurrent disease or the toxicity of treatment applied. One goal in future BFM
      trials will be to take advantage of a better molecular understanding of leukemia
      and host characteristics to dissect the mechanisms underlying the differences in
      treatment response. This short review focuses on the evolution of treatment
      response in BFM trials and provides a perspective on our strategy for improving
      molecular characterization of childhood ALL and implementing more individualized
      and novel therapeutic approaches.

PMID- 17532237
TI  - Stereoacuity is affected by induced phoria but returns toward baseline during
      vergence adaptation.
AB  - PURPOSE: In normal binocular single vision adaptation to an induced deviation
      occurs over a period of several minutes. This study investigates the effect on
      stereoacuity during vergence adaptation. METHODS: Stereoacuity, using the Frisby
      near stereotest, was measured in 20 participants aged 20.2 +/- 1.9 years with
      normal binocular single vision. Measurements were taken immediately on inducing a
      phoria with 12(Delta) base-out prisms (split), and after 3, 6, and 9 minutes of
      adaptation. A measure of stereoacuity was also taken with the same size prisms
      that were used concomitantly to control for the reduced visual acuity. RESULTS:
      Stereoacuity was found to decrease following introduction of the 12(Delta) base
      out prismatic glasses (9.4 +/- 2.5 arcsec compared with 24.4 +/- 21.4 arcsec) and
      then increase over the 9 minute period of adaptation (ANOVA, p = 0.0002). Using
      post-hoc tests with Bonferroni correction, the decrease of stereoacuity on
      introduction of the prism was significant (p = 0.0039), and although an increase
      in stereoacuity appeared to occur after 3 and 6 minutes of wearing the 12(Delta)
      glasses (14.9 +/- 4.3 arcsec, 12.3 +/- 4.5 arcsec), this did not return to the
      baseline value until 9 minutes, when the stereoacuity had increased to 12.6 +/-
      10.6 arcsec (p = 0.1982). CONCLUSIONS: In these participants, inducing a
      deviation with base-out prisms negatively affected near stereoacuity. However, as
      adaptation occurred, the level of stereoacuity was seen to increase back toward
      the baseline measurement.

PMID- 17532238
TI  - A pilot study using "ROPtool" to quantify plus disease in retinopathy of
      prematurity.
AB  - PURPOSE: The accurate diagnosis of plus disease is critical to optimize the
      timing of laser treatment. Unfortunately, it is highly subjective and error
      prone. "ROPtool" is a computer program that automatically traces retinal blood
      vessels and measures their tortuosity and dilation. Our aims were to pilot
      ROPtool, determine its reliability and validity, and establish appropriate
      numerical thresholds for plus and pre-plus disease. METHODS: Twenty high-quality
      images of the posterior poles of premature infants were collected. Two of the
      authors (DKW and SFF) independently judged tortuosity and dilation separately as
      plus, pre-plus, or normal for each quadrant of each image. Disagreements were
      adjudicated, and the results were considered to be the standard for comparison to
      ROPtool. These two authors then separately used ROPtool to analyze the same 20
      images. RESULTS: For determination of tortuosity sufficient for plus disease,
      ROPtool interuser agreement was 95% (19/20), compared with 90% (18/20) agreement
      by investigator judgment. Eye-level (2 MDs x 20 eyes) sensitivity of ROPtool in
      detecting tortuosity sufficient for plus disease averaged 95% (21/22) and
      specificity averaged 78% (14/18). Quadrant-level (2 MDs x 20 eyes x 4 quadrants)
      sensitivity averaged 85% (66/78) and specificity averaged 77% (63/82). A numeric
      threshold for pre-plus disease equal to 70% of the average tortuosity of the
      standard photograph of plus disease resulted in mean sensitivity of 89% (103/116)
      and mean specificity of 82% (36/44) in distinguishing quadrant-level tortuosity
      sufficient for pre-plus disease or worse from normal. CONCLUSIONS: ROPtool can
      reduce subjectivity and thereby enhance the evaluation of plus and pre-plus
      disease.

PMID- 17532239
TI  - Orbital melanotic neuroectodermal tumor of infancy successfully treated with
      chemotherapy and subtotal excision.
AB  - Melanotic neuroectodermal tumor of infancy is a rare condition that typically
      presents within the first 6 months of life. It rarely metastasizes but is locally
      aggressive. Melanotic neuroectodermal tumor of infancy has been reported under
      several other names including retinal anlage tumor and melanotic progonoma. Most
      commonly, melanotic neuroectodermal tumor of infancy originates in the maxilla.
      Tumors in previously reported orbital cases have arisen from adjacent structures
      or from orbital bone. Recommended treatment of melanotic neuroectodermal tumor of
      infancy has consisted of complete excision with wide tissue margins, although
      success has been reported after incomplete resection. For those patients in whom
      surgical resection is not possible, various chemotherapy approaches have been
      reported with mixed results ranging from failure to sustained tumor regression.
      We report a case of orbital melanotic neuroectodermal tumor of infancy adherent
      to sclera and successfully treated with chemotherapy and subtotal excision.

PMID- 17532240
TI  - Comparison of anterior vitrectorhexis and continuous curvilinear capsulorhexis in
      pediatric cataract and intraocular lens implantation surgery: a 10-year analysis.
AB  - PURPOSE: To analyze the rate of inadvertent anterior lens capsular tears with
      vitrectorhexis or continuous curvilinear capsulorhexis (CCC) in pediatric
      cataract and intraocular lens (IOL) implantation surgery between January 1, 1997,
      and December 31, 2006. METHODS: Retrospective chart review, collecting for each
      eye: age at cataract surgery, type of anterior capsulotomy, any tearing of the
      capsule, and if yes, details of the tear. RESULTS: A total of 737 eyes were
      reviewed. Cases with a ruptured lens capsule that occurred prior to surgery were
      excluded. Eyes that received an anterior capsulotomy by any other method (n = 27)
      or eyes that did not receive an IOL (n = 100) were reviewed but excluded from
      final comparative analysis. Of the remaining 339 eyes, 19 eyes (5.6%) were noted
      to develop an anterior capsule tear (vitrectorhexis, 12 of 226 eyes, 5.3%; CCC, 7
      of 113, 6.2%). These tears occurred during anterior capsulotomy in seven eyes,
      hydrodissection in one, cataract removal in three, and IOL insertion/manipulation
      in eight. In eyes operated for cataract at or before 72 months of age, the manual
      CCC technique was more likely to develop a tear (relative risk, 3.09) compared
      with eyes of older children (>72 months of age), where the vitrectorhexis
      technique was more likely to develop a tear (relative risk, 3.14). CONCLUSIONS:
      Vitrectorhexis is well suited for use in children less than 6 years of age due to
      their highly elastic anterior lens capsule. For children aged 6 years and older,
      manual CCC is the best technique because, by that age, capsule control and ease
      of capsulotomy completion has improved.

PMID- 17532241
TI  - The effect of the randomized trial of patching regimens for treatment of moderate
      amblyopia on pediatric ophthalmologists: 3-year outcome.
AB  - PURPOSE: To investigate whether the recommendations of the randomized trial of
      patching regimens for treatment of moderate amblyopia in children have been
      adopted by pediatric ophthalmologists 3 years after publication. METHODS: An
      identical questionnaire to that emailed 3 years ago (6 months after publication
      of the randomized trial) was emailed to 560 members of the American Association
      for Pediatric Ophthalmology and Strabismus. RESULTS: One hundred seven (20%)
      responses were received. Fifty-five percent of respondents had decreased their
      prescribed patching regimens at least sometimes as compared with 28% (p = 0.0005)
      in 2003. There was no significant increase in the prescription of near visual
      tasks or only 2 hour patching regimens. CONCLUSIONS: Our study suggests that
      pediatric ophthalmologists may be prescribing fewer patching hours in 2006 in
      comparison to 2003. However, the majority of ophthalmologists are still reluctant
      to patch for only 2 hours, and there has not been a significant increase in
      prescribing near visual tasks during patching.

PMID- 17532242
TI  - QSPR modeling of flash points: an update.
AB  - Quantitative structure-property relationship (QSPR) models for the flash points
      of 758 organic compounds are developed using geometrical, topological, quantum
      mechanical and electronic descriptors calculated by CODESSA PRO software.
      Multilinear regression models link the structures to their reported flash point
      values. We also report a nonlinear model based on an artificial neural network.
      The results are discussed in the light of the main factors that influence the
      property under investigation and its modeling.

PMID- 17532243
TI  - Seasonal variations of the energy metabolism of two sympatric species of Hyalella
      (Crustacea, Amphipoda, Dogielinotidae) in the southern Brazilian highlands.
AB  - Aquatic organisms exist in a constantly fluctuating habitat, with changes in
      photoperiod, temperature, pH, dissolved organic content, dissolved oxygen and
      food supply. Organisms must alter past of their physiological and biochemical
      processes to cope with these changes. We compared the effect of seasonal
      variations in factors related to energy metabolism of two species of sympatric
      amphipods, Hyalella pleoacuta and Hyalella castroi. The animals were collected
      monthly from April 2004 through March 2006. Contents of glycogen, proteins,
      lipids, triglycerides and the levels of lipoperoxidation were determined in males
      and females throughout the year by using spectrophotometric methods. Observations
      revealed significant seasonal differences in biochemical composition, as well as
      differences among sexes and species. Environmental conditions (e.g., trophic
      conditions) and reproduction are supposed to be the main processes influencing
      the seasonal patterns of variation in biochemical composition. Both species of
      Hyalella show ecological and behavioral differences, especially by resources such
      as food, space and seasonal variations of energy metabolism, which might
      facilitate their coexistence in the same habitat.

PMID- 17532244
TI  - [Future technological evolutions in blood donation qualification].
AB  - In the past decades, blood donation screening contributed significantly to blood
      safety improvement, thanks to the increasing performances of serological and
      nucleic acid testing (NAT) assays, as well as the evolution of automated systems
      technology. The rapid pace of NAT development can be clearly seen to extend into
      the future. NAT for additional viruses as well as the use of new automated
      systems for individual donation or smaller mini-pool testing, with multiplex
      assays, is currently debated. However, few added benefit is expected for blood
      safety from such developments, while cost-effectiveness appears to be poor. The
      next step in laboratory automation will probably be the implementation of robotic
      pre- and post-analytical procedures. In this article we review the potential
      future evolutions of screening technologies in blood qualification platforms,
      particularly those derived from nanobiotechnologies. DNA microarrays, Lab-On
      Chips, biosensors and nanoparticles (quantum dots) will probably play a major
      role in the coming decade.

PMID- 17532245
TI  - [Pisiform-hamate synostosis with ulnar neuropathy. Case report].
AB  - Entrapment of the ulnar nerve at the wrist is rare compared with the more commun
      site at the elbow. This condition was secondary to reccurent blunt trauma,
      ganglion cyst, vasculitic disorders, and fibrous bands. Compression of the ulnar
      nerve caused by pisiform-hamate coalition is rare entity. One case of this
      condition is reported.

PMID- 17532246
TI  - [Using the DRP 2.4 device for volar plating of distal radius for dorsally
      displaced wrist fractures. Report of 22 cases].
AB  - OBJECTIVE: Our first experience of palmar plating for dorsally displaced distal
      radius fracture with locking compression plate showed good results. But ancillary
      tools was ineffective, so we report our early experience with the DRP 2,4 device.
      METHODS: Between January and October 2004, 22 patients (16 women, 6 men), mean
      age 56,8 years (age range: 24-77 years), underwent internal reduction and
      fixation using DRP 2.4 by Henry's approach. By AO classification there was 10 A3
      and 12 C1 or C2 fracture. On pre operative X Ray, radial inclination was 13.9
      degrees , and dorsal tilt was 27 degrees . RESULTS: Seventeen patients were
      reviewed with mean follow-up of 11 months (5 to 17). On postoperative X Ray,
      radial inclination was 22,7 degrees and palmar tilt was 2,1 degrees. At 6 month
      radiological findings found no loss of postoperative reduction. According to
      SOFCOT's criteria's, we noticed 9 anatomical results and 8 moderate malunion.
      Clinical results (Green and O'Brien) showed 6 excellent, 7 good, 4 fair and no
      poor results. Mean DASH score was 13.5. Strength recovery was 82% of opposite
      side. Complications concerning 6 patients with, 4 reflex sympathetic dystrophy,
      and 2 screwdriver breakage during insertion. DISCUSSION: Volar plating with DRP
      2.4 is an effective technique, but obtain anatomical reduction remind challenging
      for the surgeon. CONCLUSION: DRP 2.4 volar plating is an effective treatment for
      dorsally displaced fracture. Controlled study with orthopaedic reduction and K
      Wire fixation are need for determining the place of each treatment.

PMID- 17532247
TI  - [Planned cesarean section for twin pregnancy: when the evidence-based medicine
      disturbs our convictions].

PMID- 17532248
TI  - Ultrasonically controlled particle size distribution of explosives: a safe
      method.
AB  - Size reduction of the high energy materials (HEM's) by conventional methods
      (mechanical means) is not safe as they are very sensitive to friction and impact.
      Modified crystallization techniques can be used for the same purpose. The solute
      is dissolved in the solvent and crystallized via cooling or is precipitated out
      using an antisolvent. The various crystallization parameters such as temperature,
      antisolvent addition rate and agitation are adjusted to get the required final
      crystal size and morphology. The solvent-antisolvent ratio, time of
      crystallization and yield of the product are the key factors for controlling
      antisolvent based precipitation process. The advantages of cavitationally induced
      nucleation can be coupled with the conventional crystallization process. This
      study includes the effect of the ultrasonically generated acoustic cavitation
      phenomenon on the solvent antisolvent based precipitation process. CL20, a high
      energy explosive compound, is a polyazapolycyclic caged polynitramine. CL-20 has
      greater energy output than existing (in-use) energetic ingredients while having
      an acceptable level of insensitivity to shock and other external stimuli. The
      size control and size distribution manipulation of the high energy material
      (CL20) has been successfully carried out safely and quickly along with an
      increase in the final mass yield, compared to the conventional antisolvent based
      precipitation process.

PMID- 17532249
TI  - A theoretical study of hydrodynamic cavitation.
AB  - The optimization of hydrodynamic cavitation as an AOP requires identifying the
      key parameters and studying their effects on the process. Specific simulations of
      hydrodynamic bubbles reveal that time scales play a major role on the process.
      Rarefaction/compression periods generate a number of opposing effects which have
      demonstrated to be quantitatively different from those found in ultrasonic
      cavitation. Hydrodynamic cavitation can be upscaled and offers an energy
      efficient way of generating cavitation. On the other hand, the large
      characteristic time scales hinder bubble collapse and generate a low number of
      cavitation cycles per unit time. By controlling the pressure pulse through a
      flexible cavitation chamber design these limitations can be partially
      compensated. The chemical processes promoted by this technique are also different
      from those found in ultrasonic cavitation. Properties such as volatility or
      hydrophobicity determine the potential applicability of HC and therefore have to
      be taken into account.

PMID- 17532250
TI  - Transplantation of the RPE in AMD.
AB  - The retinal pigment epithelium (RPE) maintains retinal function as the metabolic
      gatekeeper between photoreceptors (PRs) and the choriocapillaries. The RPE and
      Bruch's membrane (BM) suffer cumulative damage over lifetime, which is thought to
      induce age-related macular degeneration (AMD) in susceptible individuals. Unlike
      palliative pharmacologic treatments, replacement of the RPE has a curative
      potential for AMD. This article reviews mechanisms leading to RPE dysfunction in
      aging and AMD, laboratory studies on RPE transplantation, and surgical techniques
      used in AMD patients. Future strategies using ex vivo steps prior to
      transplantation, BM prosthetics, and stem cell applications are discussed. The
      functional peculiarity of the macular region, epigenetic phenomena leading to an
      age-related shift in protein expression, along with the accumulation of
      lipofuscin may affect the metabolism in the central RPE. Thickening of BM with
      age decreases its hydraulic conductivity. Drusen are deposits of extracellular
      material and formed in part by activation of the alternative complement pathway
      in individuals carrying a mutant allele of complement factor H. AMD likely
      represents an umbrella term for a disease entity with multifactorial etiology and
      manifestations. Presently, a slow progressing (dry) non-neovascular atrophic form
      and a rapidly blinding neovascular (wet) form are discerned. No therapy is
      currently available for the former, while RPE transplantation and promising
      (albeit non-causal) anti-angiogenic therapies are available for the latter. The
      potential of RPE transplantation was demonstrated in animal models. Rejection of
      allogeneic homologous transplants in patients focused further studies on
      autologous sources. In vitro studies elucidated cell adhesion and wound healing
      mechanisms on aged human BM. Currently, autologous RPE, harvested from the
      midperiphery, is being transplanted as a cell suspension or a patch of RPE and
      choroid in AMD patients. These techniques have been evaluated from several
      groups. Autologous RPE transplants may have the disadvantage of carrying the same
      genetic information that may have led to AMD manifestation. An intermittent
      culturing step would allow for in vitro therapy of the RPE, its rejuvenation and
      prosthesis of BM to improve the success RPE transplants. Recent advances in stem
      cell biology when combined with lessons learned from studies of RPE
      transplantation are intriguing future therapeutic modalities for AMD patients.

PMID- 17532251
TI  - A pharmacoepidemiological study of the consumption of antiparkinson drugs in the
      Basque Autonomous Community (Spain) (1992-2004).
AB  - PURPOSE: To monitor the rise in consumption of antiparkinson drugs as well as the
      prevalence of this illness in the Basque Autonomous Community (Spain) over a
      period of 13 years (1992-2004). METHODS: A retrospective population-based study
      where consumption of antiparkinson drugs was conducted using data obtained from
      the ECOM (Especialidades Consumo de Medicamentos) database of the Spanish
      Ministry of Health, which contains the number of prescriptions filled in
      community pharmacies and charged to the National Health System. The results are
      expressed as DID, Defined daily doses per 1000 inhabitants per day. CONCLUSIONS:
      Consumption of antiparkinson drugs has increased in the Basque Autonomous
      Community.

PMID- 17532252
TI  - Pre-manipulative testing and the use of the velocimeter.
AB  - Manipulation of the cervical spine remains a common intervention for neck pain
      and dysfunction, despite the well-documented associated risk of vertebrobasilar
      stroke. The currently advocated pre-manipulative risk assessment protocols
      include the use of provocative positional tests to challenge the integrity of the
      vascular supply to the brain. This paper critically evaluates the validity of
      these pre-manipulative provocative tests in the light of ultrasonographic blood
      flow studies of the vertebral arteries. It also critically evaluates the evidence
      concerning the clinical utility of a portable continuous wave Doppler device (or
      velocimeter) to examine vertebral artery blood flow prior to neck manipulation.
      There is clear evidence that the provocative tests may produce both false
      positive and false negative findings. Initial research regarding the clinical use
      of a velocimeter suggests this device may provide a more objective assessment of
      vertebral artery blood flow than the provocative tests. However, the sensitivity,
      specificity and reliability of the use of the velocimeter in identifying abnormal
      vascular flow in the vertebral arteries, and therefore its clinical utility, has
      not yet been fully established.

PMID- 17532253
TI  - RNA structure: experimental analysis.
AB  - Among all of the biological macromolecules, the functional versatility of RNAs is
      unique including encoding or transferring genetic information and performing
      catalysis. These biological functions are highly dependent upon RNA folding and
      structure. Since the discovery of catalytic RNAs in the early 1980s, a recent
      breakthrough came from the identification of a wealth of micro RNAs, small
      interfering RNAs and regulatory RNAs, all involved in modulation of gene
      expression. The structure of these novel RNAs, either free or in complex with
      specific ligands, can be analyzed using various experimental strategies,
      including X-ray crystallography, cryo-electron microscopy, nuclear magnetic
      resonance spectroscopy, structure-specific probes, with some that can be used in
      living cells, RNA engineering, thermal denaturation and mass spectrometry. Among
      these, X-ray crystallography has recently enabled determination of the structures
      of several large and complex RNAs, as well as of ribonucleoprotein complexes. The
      database of RNA structure has grown tremendously since the recent crystal
      structure analyses of the prokaryotic ribosome and its subunits. These methods
      are now widely applied to a variety of biologically relevant RNAs.

PMID- 17532254
TI  - Cell killing, nuclear damage and apoptosis in Chinese hamster V79 cells after
      irradiation with heavy-ion beams of (16)O, (12)C and (7)Li.
AB  - Chinese hamster V79 cells were exposed to high LET (linear energy transfer) (16)O
      beam (625keV/mum) radiation in the dose range of 0-9.83Gy. Cell survival,
      micronuclei (MN), chromosomal aberrations (CA) and induction of apoptosis were
      studied as a follow up of our earlier study on high LET radiations ((7)Li-beam of
      60keV/mum and (12)C-beam of 295keV/mum) as well as (60)Co gamma-rays. Dose
      dependent decline in surviving fraction was noticed along with the increase of MN
      frequency, CA frequency as well as percentage of apoptosis as detected by nuclear
      fragmentation assay. The relative intensity of DNA ladder, which is a useful
      marker for the determination of the extent of apoptosis induction, was also
      increased in a dose dependent manner. Additionally, expression of tyrosine kinase
      lck-1 gene, which plays an important role in response to ionizing radiation
      induced apoptosis, was increased with the increase of radiation doses and also
      with incubation time. The present study showed that all the high LET radiations
      were generally more effective in cell killing and inflicting other cytogenetic
      damages than that of low LET gamma-rays. The dose response curves revealed that
      (7)Li-beam was most effective in cell killing as well as inducing other nuclear
      damages followed by (12)C, (16)O and (60)Co gamma-rays, in that order. The result
      of this study may have some application in biological dosimetry for assessment of
      genotoxicity in heavy ion exposed subjects and in determining suitable doses for
      radiotherapy in cancer patients where various species of heavy ions are now being
      generally used.

PMID- 17532255
TI  - The cda GenoTox assay: a new and sensitive method for detection of environmental
      genotoxins, including nitroarenes and aromatic amines.
AB  - A new bacterial test system for detection of genotoxic compounds was developed,
      based on two new Salmonella typhimurium tester strains, TGO1 and TGO2. Both
      strains contain a gene fusion between a strong SOS-promotor, P(cda), and the gfp
      gene, which allows detection of genotoxic compounds that induce the SOS response.
      SOS induction was detected by means of flow cytometry. TGO1 showed an increased
      sensitivity to N-methyl-N'-nitro-N-nitrosoguanidine compared with a previously
      developed strain, which had an Escherichia coli strain as host instead of S.
      typhimurium. S9 mix was introduced into the assay, making the test system
      suitable for detection of indirect mutagens. Furthermore, the genes for bacterial
      nitro-reductase (NR) and o-acetyl transferase (o-AT) were inserted into TGO2,
      making it an NR- and o-AT-over-expressing strain. This resulted in an assay that
      was able to detect the nitroarene 1-nitropyrene and the aromatic amine 2
      aminoanthracene with high sensitivity.

PMID- 17532256
TI  - Evaluation of general practitioner's time investment during a store-and-forward
      teledermatology consultation.
AB  - BACKGROUND/OBJECTIVE: Introduction of teledermatology in general practice changes
      responsibilities and workloads of general practitioners (GPs) and dermatologists.
      We investigated the time investment of GPs as well as the relative share of the
      separate teledermatology activities during a store-and-forward teledermatology
      consultation. METHODS: Sixty-four teledermatology consultations (eight GPs x
      eight patients) were conducted in a laboratory setting. The starting and ending
      time of each consultation and of five separate teledermatology activities were
      recorded by independent observers. The impact of several GP, patient and
      consultation characteristics on the calculated durations was investigated with
      repeated measurements analysis. RESULTS: The mean duration of a teledermatology
      consultation was 11:32 min (range 7:02-26:44 min). The activity 'filling out
      electronic referral form' was the most time consuming teledermatology activity
      (3:12 min; 28%). Most time was spent on non-TD related consultation activities,
      e.g. taking medical history (4:43 min; 41%). The first of the eight consultations
      (p<0.001) and consultations with female patients (p=0.032) took on average more
      time than subsequent consultations (first consultations 13:42 min (male patients)
      and 17:03 min (female patients), and subsequent consultations 9:56 min (male
      patients) and 11:08 min (female patients)). CONCLUSIONS: Usage of store-and
      forward teledermatology increases the average duration of a GP consultation with
      at least three and a half minutes. Further integration of teledermatology
      applications and electronic patients' records may reduce the total duration of a
      consultation and increase acceptance of teledermatology in general practice.

PMID- 17532257
TI  - Impaired quantification of plasma HIV-1 RNA with a commercialized real-time PCR
      assay in a couple of HIV-1-infected individuals.

PMID- 17532258
TI  - Antibiotic use in children is not influenced by the result of rapid antigen
      detection test for the respiratory syncytial virus.
AB  - BACKGROUND: Rapid antigen detection test (RADT) for respiratory syncytial virus
      (RSV) is widely used in children hospitalized with acute respiratory tract
      infection (ARTI), but its influence on antibiotic (AB) use is uncertain.
      OBJECTIVE: To evaluate if confirmation of RSV infection by RADT modified AB use
      and elucidate others factors associated with the continuation of antibiotics.
      STUDY DESIGN: Charts of children hospitalized with viral ARTI aged 0-35 months
      were reviewed. Modification of antibiotics according to RSV RADT results was
      compared using Kaplan-Meier estimates and multivariate Cox regression. RESULTS:
      Of children receiving antibiotics when the RSV RADT result was available, RSV
      RADT was positive in 144 and negative in 54. Positive RSV RADT results did not
      lead to modification of antibiotic use. Factors independently associated with
      cessation of intravenous antibiotics were age > or = 3 months (HR 2.44 [1.41
      4.21]) and absence of pneumonia (HR 1.50 [1.03-2.19]). Absence of otitis was
      associated with cessation of oral antibiotics (HR 9.16 [95% CI, 2.35-35.76]).
      CONCLUSION: Confirmed presence of RSV by RADT did not influence antibiotic use in
      young children with ARTI. Except with pneumonia, the risk of bacterial
      superinfection of RSV infected children is minimal and confirmation of RSV
      infection should prompt treating physicians to interrupt antibiotics.

PMID- 17532259
TI  - Auditory event-related potentials and cognitive function of preterm children at
      five years of age.
AB  - OBJECTIVE: In our previous study, auditory event-related potentials (AERPs) in
      preterm 1-year-old children had a positive deflection at 150-350 ms that
      correlated positively with their 2-year neurodevelopmental outcome. In a study of
      the same subjects at age 5, our aim was to assess AERPs and their relationship to
      neuropsychological test results. METHODS: Preterm small (SGA, n=13), appropriate
      for gestational age (AGA, n=15), and control (n=13) children were assessed with
      an Easy paradigm presenting a large frequency change accompanied with occasional
      novel sounds, and a Challenging paradigm presenting small frequency and duration
      changes with a rapid rate. The preterm children underwent neurocognitive tests.
      RESULTS: Easy paradigm. The P1 response to frequency deviant was smaller and MMN
      larger in the preterm than in the control children. Challenging paradigm. The P1
      response to standard, frequency, and duration deviants was smaller in the preterm
      than in the control children. The N2 response to frequency deviant was larger in
      the preterm than in the control children. AGA and SGA children had similar AERPs.
      The P1, N2, and MMN amplitudes correlated with verbal IQ and NEPSY language
      subtests. CONCLUSIONS: Small P1 response(s) appears to be typical for preterm
      children. SIGNIFICANCE: Small P1 response in preterm children may suggest altered
      primary auditory processing.

PMID- 17532260
TI  - Electrophysiological abnormalities of spatial attention in adults with autism
      during the gap overlap task.
AB  - OBJECTIVE: We evaluated event-related potentials (ERPs) elicited by attentional
      disengagement in individuals with autism. METHODS: Sixteen adults with autism, 17
      adults with mental retardation and 14 healthy adults participated in this study.
      We recorded the pre-saccade positive ERPs during the gap overlap task under which
      a peripheral stimulus was presented subsequent to a stimulus in the central
      visual field. Under the overlap condition, the central stimulus remained during
      the presentation of the peripheral stimulus and therefore participants need to
      disengage their attention intentionally in order to execute the saccade to the
      peripheral stimulus due to the preservation of the central stimulus. RESULTS: The
      autism group elicited significantly higher pre-saccadic positivity during a
      period of 100-70 ms prior to the saccade onset than the other groups only under
      the overlap condition. The higher amplitude of pre-saccadic positivity in the
      overlap condition was significantly correlated with more severe clinical symptoms
      within the autism group. CONCLUSIONS: These results demonstrate
      electrophysiological abnormalities of disengagement during visuospatial attention
      in adults with autism which cannot be attributed to their IQs. SIGNIFICANCE: We
      suggest that adults with autism have deficits in attentional disengagement and
      the physiological substrates underlying deficits in autism and mental retardation
      are different.

PMID- 17532261
TI  - Influence of pyruvate on economy of contraction in isolated rabbit myocardium.
AB  - BACKGROUND: Treatment of acute heart failure frequently requires positive
      inotropic stimulation. However, there is still no inotropic agent available,
      which combines a favourable haemodynamic profile with low expenditure for energy
      metabolism. Pyruvate exhibits positive inotropic effects in vitro and in patients
      with heart failure. The effect on myocardial energy metabolism however remains
      unclear, but is meaningful in light of a clinical application. AIMS AND METHODS:
      We investigated the influence of pyruvate on contractility and oxygen consumption
      in isolated isometric contracting rabbit myocardium compared to beta-adrenergic
      stimulation with isoproterenol. RESULTS: Pyruvate (30 mM) increased developed
      force from 18.7+/-4.1 to 50.8+/-12.1 mN/mm2 (n=10, p<0.01). Force-time integral
      (FTI) increased by 329%, oxygen consumption assessed by diffusion-microelectrode
      technique increased from 2.86+/-0.30 mlO2/min*100 g to 6.28+/-1.28 mlO2/min*100 g
      (n=7, p<0.05). Economy of myocardial contraction calculated as the ratio of total
      FTI to oxygen consumption remained unchanged. In contrast, while isoproterenol
      (10 microM) produced a comparable increase in developed force from 21.4+/-8.3 to
      67.3+/-15 mN/mm2 (n=7, p<0.01), FTI increased only by 260% and MVO2 increased
      from 2.96+/-0.43 to 6.12+/-1.01 mlO2/min*100 g (n=7, p<0.01); thus, economy
      decreased by 23% (n=7, p<0.05). CONCLUSION: Pyruvate does not impair economy of
      myocardial contraction while isoproterenol decreases economy. Regarding energy
      expenditure, pyruvate appears superior to isoproterenol for the purpose of
      positive inotropic stimulation.

PMID- 17532262
TI  - Anaemia and renal dysfunction are independently associated with BNP and NT-proBNP
      levels in patients with heart failure.
AB  - BACKGROUND: Anaemia may affect B-type natriuretic peptide (BNP) and N-terminal
      proBNP (NT-proBNP) levels, but this has not been well described in heart failure
      (HF) patients without the exclusion of patients with renal dysfunction. AIMS: To
      study the influence of both anaemia and renal function on BNP and NT-proBNP
      levels in a large group of hospitalised HF patients. METHODS AND RESULTS: We
      studied 541 patients hospitalised for HF (mean age 71+/-11 years, 62% male, and
      left ventricular ejection fraction 0.33+/-0.14). Of these patients, 30% (n=159)
      were anaemic (women: Hb<7.5 mmol/l, men: Hb<8.1 mmol/l). Of the 159 anaemic
      patients, 73% had renal dysfunction (eGFR<60 ml/min/1.73 m2) and of the non
      anaemic patients, 57% had renal dysfunction. BNP and NT-proBNP levels were
      measured in all patients before discharge. In multivariable analyses both plasma
      haemoglobin and eGFR were independently related to the levels of BNP and NT
      proBNP (standardised beta's of -0.16, -0.14 [BNP] and -0.19, -0.26 [NT-proBNP]
      respectively, P-values<0.01). CONCLUSION: Anaemia and renal dysfunction are
      related to increased BNP and NT-proBNP levels, independent of the severity of HF.
      These results indicate that both anaemia and renal dysfunction should be taken
      into consideration during the interpretation of BNP and NT-proBNP levels in HF
      patients.

PMID- 17532263
TI  - Heart transplantation in heart failure: the prognostic importance of body mass
      index at time of surgery and subsequent weight changes.
AB  - BACKGROUND: Heart transplantation is an important treatment for end-stage chronic
      heart failure. We studied the effect of body mass index (BMI), and the effect of
      subsequent weight change, on survival following transplantation in 1902
      consecutive patients. METHODS AND RESULTS: Patients were recruited from: London
      (n=553), Berlin (N=971) and Boston (N=378). Patients suitable for transplantation
      due to symptoms, low left ventricular ejection fraction (<or=30%) and peak oxygen
      consumption (<or=16 ml kg(-1) min(-1)) (N=237) were used as a comparator. In
      surviving transplanted patients, average duration of follow-up was 80 (SD 34)
      months. There were 805 deaths. One year survival was 72.7% (95% CI 72.68-72.72)
      and 5 year survival was 60.96% (61.94-61.99). Baseline BMI did not effect
      survival either as a continuous variable (hazard ratio (95% CI): 1.02; 0.99
      1.04). Weight loss between transplant and 3 months was associated with worse
      survival (HR (95% CI) 2.6 (1.42-4.74)) compared with those who gained weight. In
      the reference group, increasing body mass index was related to survival.
      CONCLUSIONS: Chronic heart failure patients with very low body weight can be
      transplanted successfully. The presence of underweight need not be an exclusion
      criterion for heart transplantation. Underweight patients appear to have a
      greater benefit from transplantation. Body weight increases after transplantation
      are not associated with adverse prognosis.

PMID- 17532264
TI  - Cellular behavior of neointima-like cells onto vitamin E-enriched poly(D,L)lactic
      acid.
AB  - In-stent restenosis is a process that occurs in 10-50% of cases currently treated
      with stent and it is caused by an abnormal smooth muscle cell (SMC) proliferation
      and migration in the vascular lumen. One of the most promising strategy to reduce
      restenosis is stent coating with biodegradable polymers to deliver in situ anti
      proliferative drugs. Poly(D,L)lactic acid (P(D,L)LA), one of the most interesting
      candidate for stent coating, has been observed to induce inflammation and
      neointimal proliferation. In our laboratory, we developed P(D,L)LA enriched with
      Vitamin E (Vit.E), an anti-oxidative and anti-inflammatory agent that reduces
      also SMC proliferation. In order to evaluate the in vitro cellular behaviour of
      neointima cells onto Vitamin E-enriched P(D,L)LA, cell adhesion and proliferation
      along with the expression of two SMC migration markers (MMP-9 and hyaluronic acid
      receptor CD44) were measured in rat vascular SMC A10 cells seeded onto control
      P(D,L)LA (PLA) and P(D,L)LA films containing 10-30% (w/w) Vit.E (PLA10-30). Cell
      adhesion, proliferation and MMP-9 production were unaffected by the Vit.E
      presence in the PLA films after 24 h, while proliferation was slowed or blocked
      after 48 and 72 h onto PLA10, 20 and 30. MMP-9 production was almost blocked and
      CD44 density decreased significantly after 72 h for cells grew onto PLA30 compare
      to cells seeded onto PLA. These data indicate that Vit.E-enriched P(D,L)LA could
      be an interesting polymer for stent coating.

PMID- 17532265
TI  - Interferon gamma/IL10 ratio defines the disease severity in pulmonary and extra
      pulmonary tuberculosis.
AB  - Several cytokines (IFN gamma, TNF alpha, IL10 and IL6) show an association with
      either disease localization or dissemination in tuberculosis. There are also
      reports of involvement of extra-pulmonary sites in tuberculosis with differential
      clinical severity. However, no comparative study of biomarkers across the disease
      severity spectrum is available. This was the purpose of the current study.
      Cytokines (IFN gamma, TNFalpha, IL10 and IL6) secreted in response to a panel of
      stimulants (PHA, LPS or mycobacterial antigens) in whole blood were determined in
      eighty-two tuberculosis patients. WHO criteria was applied for stratification of
      patients according to disease severity: disseminated and or severe disease
      (EPTB1; N=29); disease localized to lung parenchyma (PTB; N=32) and disease
      localized to peripheral sites without lung involvement (EPTB2; N=21).
      Mycobacterial antigens induced IFN gamma/IL10 ratio showed a direct relationship
      with disease severity ranking (median ratios: EPTB1=0.21; PTB=0.85; EPTB2=7.7)
      and the highest correlation (Spearman Rank; rho=0.673, p<0.000001). IFN
      gamma/IL10 ratio also rank ordered clinical severity as it relates to anatomic
      sites. IFN gamma/IL10 ratio may therefore provide a useful objective marker of
      disease severity in both pulmonary and extra-pulmonary tuberculosis.

PMID- 17532266
TI  - A community study of the presence of anxiety disorder in people with epilepsy.
AB  - Anxiety represents a major problem for people with epilepsy, and it is important
      to understand why it arises and how to reduce its potential debilitating and
      adverse effects. The aim of this study was to determine the prevalence of anxiety
      in a community-identified sample of people with epilepsy and to identify which
      demographic and clinical factors are most closely associated with anxiety and
      which factors predict the presence of anxiety among people with epilepsy. Adults
      with epilepsy in the community (n=515) were identified through primary care
      records and sent validated questionnaires, which included the Hospital Anxiety
      and Depression Scale (HADS). The mailout also included items on demographic and
      clinical variables. The prevalence of anxiety (HADS score >11) in this sample was
      20.5% (95% CI: 16.9-24.1%) and was associated with a current history of
      depression, perceived side effects of antiepileptic medication, lower educational
      attainment, chronic ill health, female gender, and unemployment. It was not
      associated with the duration of epilepsy. The findings from this study suggest
      that anxiety disorders in a community population with epilepsy are most strongly
      predicted by factors independent of epilepsy-related variables, with the
      exception of patient-reported side effects. It is important to be aware of these
      factors when evaluating an individual with epilepsy.

PMID- 17532267
TI  - Diabetes-induced chemogenic hypoalgesia is paralleled by attenuated stimulus
      induced fos expression in the spinal cord of diabetic mice.
AB  - Chronic hyperglycemia in diabetes induces abnormal nerve pathologies, resulting
      in diabetic neuropathy (DN). Sensory symptoms of DN can manifest as positive
      (painful), negative (insensate), or both. Streptozotocin (STZ)-induced diabetic
      C57Bl/6 mice have reduced cutaneous innervation and display reduced behavioral
      responses to noxious stimuli, reflecting the insensate aspect of the human
      syndrome. Current studies were undertaken to determine whether the diabetes
      induced deficits in pain responses are reflected by changes in spinal activation
      in this model of DN. Nocifensive responses of nondiabetic and diabetic mice to
      formalin injection were measured 1, 3, 5, and 7 weeks after STZ, and at each time
      point formalin-induced spinal Fos expression was quantified. Responses of
      diabetic mice were significantly reduced during the second phase of the formalin
      test beginning 3 weeks after STZ and during Phase 1 beginning 5 weeks after STZ.
      Consistent with the behavioral responses, the number of Fos-positive cells in the
      dorsal horn of diabetic animals was significantly reduced beginning 3 weeks after
      STZ and continuing 5 and 7 weeks after STZ. The deficits at 5 weeks after STZ
      were restored by 2-week treatments with insulin or neurotrophins. These results
      demonstrate that the reduced sensation occurring from progressive peripheral axon
      loss results in functional deficits in spinal cord activation. PERSPECTIVE: The
      reduced expression of the immediate early gene Fos as an indicator of pain
      transmission supports the diabetes-induced loss of sensation in this Type 1 model
      of diabetes. This murine model may be better suited to understanding the
      insensate symptoms of diabetic patients in the absence of chronic pain.

PMID- 17532268
TI  - Comparative analysis of short-term outcomes after bariatric surgery between two
      disparate populations.
AB  - BACKGROUND: Risk adjustment is a critically important aspect of outcomes
      research. Racial, geographic, cultural, and socioeconomic differences are
      nonclinical parameters that can affect clinical outcomes measurement after
      gastric bypass surgery. METHODS: A single surgeon's experience with 217
      consecutive laparoscopic gastric bypass patients in private practice in Southern
      California was compared with the same surgeon's experience with 124 consecutive
      patients in an academic institution in Philadelphia. RESULTS: Of the Southern
      California and Philadelphia groups, 89%, 1%, 9%, and 1% and 55%, 38%, 6%, and 0%
      were white, black, Hispanic, and Asian, respectively. The average number of co
      morbidities was 7.8 in the Southern California group versus 14.4 in the
      Philadelphia group (P <.001). The 60-day readmission to the hospital rate and
      emergency room admission rate was 1.4% versus 10.4% and 1.4% versus 18.5%. The
      insurer mix of private pay, private insurer, and federally funded insurer was
      20%, 80%, and 0% in the Southern California group and 0.8%, 71%, and 28% in the
      Philadelphia group, respectively. Multivariate logistic regression analysis found
      Medicaid status and practice location independently predicted for the 60-day
      readmission rate (odds ratio [OR] 3.7, P = .04 and OR 5.6, P = .04, respectively)
      and a return to the emergency room (OR 3.2, P = .03 and OR 16.3, P <.001). Race,
      income, and the presence of diabetes were not independent predictors. Variables
      with nonsignificant differences between the Southern California and Philadelphia
      cohorts included average age, average body mass index, and major complications
      (return to surgery and intensive care unit admissions). CONCLUSION: The results
      of this study have shown that in comparing and predicting the outcomes after
      bariatric surgery, adjustment for demographic and insurance variables might be
      necessary to improve accuracy.

PMID- 17532269
TI  - Does reproduction decrease longevity in human beings?
AB  - According to the disposable soma theory, a cost for reproduction could exist in
      human beings and other species and, thus, longevity could decrease when women
      have a higher number of children. The purpose of this article is to review the
      evidence in populations living or not living under natural fertility conditions,
      i.e. when fertility is near its biological maximum. The results indicate that in
      natural fertility conditions longevity does not decrease when the number of
      children increases but, in modern populations, mortality could slightly increase
      when women have more than ca 5 children. Complete data for these modern cohorts
      will tell us, one day, whether these results are still observed when the variable
      of interest is longevity and not only mortality.

PMID- 17532271
TI  - Transmission of Pseudomonas aeruginosa in children with cystic fibrosis attending
      summer camps in The Netherlands.
AB  - BACKGROUND: Cross-infection of Pseudomonas aeruginosa has been reported to occur
      at holiday camps for children with Cystic Fibrosis (CF) with varying frequency.
      The study aimed to establish the degree of transmission resulting in subsequent
      infection of P. aeruginosa among CF children (n=80) attending holiday camps in
      The Netherlands. METHODS: The study was performed in the summer of 2001 in four
      camps organised simultaneously at different locations. Sputum was collected on
      day 1 of the holiday, and three and six months later. Different morphotypes of P.
      aeruginosa from sputum were genotyped by AFLP analysis. Criteria were defined for
      the degree of evidence of transmission. RESULTS: There were 18 cases possible, 2
      cases of probable transmission and 1 case of highly probable transmission. Two
      predominant types of P. aeruginosa were found (types 18 and 23). Type 18 was
      already prevalent on day 1 mostly in younger children and was involved in eleven
      cases of transmission; type 23 was involved in six cases of transmission among
      older children. CONCLUSIONS: There was a considerable risk of transmission of P.
      aeruginosa during holiday camps for CF children in The Netherlands. Two genotypes
      of P. aeruginosa appeared to be easily transmissible, one of which seemed common
      in the Dutch CF population.

PMID- 17532270
TI  - Transcription coupled nucleotide excision repair in Escherichia coli can be
      affected by changing the arginine at position 529 of the beta subunit of RNA
      polymerase.
AB  - The proposed mechanism for transcription coupled nucleotide excision repair (TCR)
      invokes RNA polymerase (RNAP) blocked at a DNA lesion as a signal to initiate
      repair. In Escherichia coli, TCR requires the interaction of RNAP with a
      transcription-repair coupling factor encoded by the mfd gene. The interaction
      between RNAP and Mfd depends upon amino acids 117, 118, and 119 of the beta
      subunit of RNAP; changing any one of these to alanine diminishes the interaction
      [1]. Using direct assays for TCR, and the lac operon of E. coli containing UV
      induced cyclobutane pyrimidine dimers (CPDs) as substrate, we have found that a
      change from arginine to cysteine at amino acid 529 of the beta subunit of the
      RNAP inactivates TCR, but does not prevent the interaction of RNAP with Mfd. Our
      results suggest that this interaction may be necessary but not sufficient to
      facilitate TCR.

PMID- 17532272
TI  - Pathogenesis of pulmonary edema: learning from high-altitude pulmonary edema.
AB  - Pulmonary edema is a problem of major clinical importance resulting from a
      persistent imbalance between forces that drive water into the airspace of the
      lung and the biological mechanisms for its removal. Here, we will review the
      fundamental mechanisms implicated in the regulation of alveolar fluid
      homeostasis. We will then describe the perturbations of pulmonary fluid
      homeostasis implicated in the pathogenesis of pulmonary edema in conditions
      associated with increased pulmonary capillary pressure, namely cardiogenic
      pulmonary edema and high-altitude pulmonary edema (HAPE), with particular
      emphasis on the latter that has provided important new insight into underlying
      mechanisms of pulmonary edema. We will provide evidence that impaired pulmonary
      endothelial and epithelial nitric oxide synthesis and/or bioavailability may
      represent a central underlying defect predisposing to exaggerated hypoxic
      pulmonary vasoconstriction, and, in turn, capillary stress failure and alveolar
      fluid flooding. We will then demonstrate that exaggerated pulmonary hypertension,
      while possibly a prerequisite, may not always be sufficient to cause HAPE, and
      how defective alveolar fluid clearance may represent a second important
      pathogenic mechanism. Finally, we will outline, how this new insight gained from
      studies in HAPE, may be translated into the management of pulmonary edema and
      hypoxemia related disease states in general.

PMID- 17532273
TI  - Factors affecting clinical and endoscopic efficacies of selective
      leucocytapheresis for ulcerative colitis.
AB  - BACKGROUND: Granulocyte, monocyte/macrophage adsorptive apheresis is a novel
      treatment for active ulcerative colitis. However, as yet no study has reported on
      a subset of patients who might respond well to granulocyte, monocyte/macrophage
      adsorptive apheresis therapy. AIM: To identify factors affecting clinical and
      endoscopic efficacies of granulocyte, monocyte/macrophage in patients with
      ulcerative colitis. METHODS: Fifty consecutive patients with active ulcerative
      colitis initially received five granulocyte, monocyte/macrophage adsorptive
      apheresis sessions with the Adacolumn over five consecutive weeks. Patients who
      improved without achieving remission received five additional granulocyte,
      monocyte/macrophage adsorptive apheresis sessions. RESULTS: One week after the
      last granulocyte, monocyte/macrophage adsorptive apheresis session, 26 (52%) and
      17 patients (34%) achieved clinical and endoscopic remission, respectively. In
      the multivariate analysis, the dose of prednisolone administered at entry and the
      cumulative dose of prednisolone administered before entry were independent
      significant factors for both clinical and endoscopic remission, negatively
      impacted the efficacy of granulocyte, monocyte/macrophage adsorptive apheresis.
      Age, gender, duration of ulcerative colitis, number of prior relapses, duration
      of current exacerbation, extent and severity of ulcerative colitis, extra
      intestinal manifestations, entry haematology values and C-reactive protein did
      not affect the outcome. CONCLUSIONS: Based on the outcomes of this study, it
      appears that steroid-naive patients and patients on low dose steroid and short
      duration of exposure respond to granulocyte, monocyte/macrophage adsorptive
      apheresis. Further studies in larger cohorts of patients should strengthen our
      findings.

PMID- 17532274
TI  - Evaluation of an instrument for the surveillance of adult gluten intolerance
      diagnosis: Report of the first year of activity of the Campania Celiac Network
      for Adult Celiac Disease.

PMID- 17532275
TI  - Micro- and nano-injectable composite biomaterials containing calcium phosphate
      coated with poly(DL-lactide-co-glycolide).
AB  - Calcium phosphate/poly(dl-lactide-co-glycolide) (CP/DLPLG) composite biomaterial,
      in which each CP particle was coated with DLPLG, was synthesized. Two kinds of
      composites were prepared: microcomposite, with particles 150-200mum in size, and
      nanocomposite, with the particles 40+/-5nm in size. Using nanoparticles, a new
      class of injectible composite biomaterials was produced. Based on scanning
      electron microscopy, atomic force microscopy, differential thermal analysis,
      thermogravimetric analysis, differential scanning calorimetry and Fourier
      transform infrared analyses, the structure and phase organization in both
      biomaterials was identified and in both studied cases CP particles were coated
      with DLPLG polymer. An injectable composite biomaterial, the characteristics of
      which depend on the ratio of the phases, was prepared by mixing physiological
      solution with the nano-CP/DLPLG composite. Rheological studies indicated a
      possible agglomeration of particles of the injectable nano-CP/DLPLG composite
      biomaterial with a CP content of 65%.

PMID- 17532276
TI  - A dual-functional fibrous scaffold enhances P450 activity of cultured primary rat
      hepatocytes.
AB  - We have designed a novel dual-functional electrospun fibrous scaffold comprising
      two fiber mesh layers that were modified differently to induce two separate
      biological responses from hepatocytes. The first fiber layer was galactosylated
      on the surface to mediate hepatocyte attachment, while the second layer was
      loaded with 3-methylcholanthrene (3-Mc) to enhance cytochrome P450 activity of
      hepatocytes. Primary rat hepatocytes cultured on the galactosylated fibrous
      scaffolds loaded with different concentrations of 3-Mc were compared for their
      cell attachment efficiency, albumin secretion activity and cytochrome P450
      dependent 7-ethoxycoumarin O-deethylase activity. This hybrid fibrous scaffold
      mediated hepatocyte attachment with slightly lower efficiency (76+/-2.3%) than a
      single-layer galactosylated fibrous scaffold (84+/-3.5%). More importantly, the
      cytochrome P450 activity of the hepatocytes cultured on the hybrid scaffold
      correlated well with the 3-Mc loading level. The results also showed that
      transfer of 3-Mc to hepatocytes through direct cell-fiber contact was the
      dominant transport route, with the induced cytochrome P450 activity being 1.9- to
      4.8-fold higher than that of transfer of 3-Mc to hepatocytes via dissolution from
      fibers to medium. This study demonstrates the feasibility of creating multi
      functional fibrous scaffolds that serve both as an adhesive substrate and as a
      delivery vehicle for bioactive molecules.

PMID- 17532277
TI  - Low stiffness porous Ti structures for load-bearing implants.
AB  - The need for unique mechanical and functional properties coupled with
      manufacturing flexibility for a wide range of metallic implant materials
      necessitates the use of novel design and fabrication approaches. In this work, we
      have demonstrated that application of proposed design concepts in combination
      with laser-engineered net shaping (LENStrade mark) can significantly increase the
      processing flexibility of complex-shaped metallic implants with three
      dimensionally interconnected, designed and functionally graded porosities down to
      70vol.%, to reduce effective stiffness for load-bearing implants. Young's modulus
      and 0.2% proof strength of these porous Ti samples having 35-42vol.% porosity are
      found to be similar to those of human cortical bone.

PMID- 17532278
TI  - Continuous postoperative monitoring of cutaneous free flaps using near infrared
      spectroscopy.
AB  - Reliable detection of circulatory compromise threatening free-flap viability is
      essential for prompt surgical intervention and flap salvage. Numerous techniques
      have been developed to address the issue of postoperative flap monitoring but
      none have achieved universal acceptance. Near infrared spectroscopy (NIRS) is a
      noninvasive technique that allows continuous monitoring of tissue oxygenation and
      perfusion. It is increasingly recognised to be a reliable method for flap
      viability assessment. This study was designed to investigate the ability of NIRS
      to detect and identify microvascular thrombosis endangering flap survival. To our
      knowledge, this is the first clinical evaluation of NIRS used for continuous
      monitoring of free flaps. METHODS: Fifty flaps used for autologous breast
      reconstruction in 48 patients were included in this prospective clinical study.
      NIRS was employed for 72-h continuous postoperative monitoring. The data were
      compared to findings of clinical assessments. RESULTS: Ten flaps (20%) developed
      13 anastomosis thromboses (two arterial and 11 venous). NIRS detected all cases
      of flow failure prior to clinical observation with no false positives or
      negatives. Based on consistent patterns of NIRS parameter changes, it was
      possible to differentiate between changes caused by arterial and venous
      thrombosis with accuracy before surgical re-exploration. The salvage rate was
      70%. Overall flap viability was 94%. CONCLUSIONS: Continuous NIRS monitoring can
      reliably detect and identify early stages of arterial and venous thrombosis, and
      is a credible method for noninvasive postoperative flap surveillance. Based on
      these findings, we advocate its use for monitoring of flaps with a cutaneous
      component.

PMID- 17532279
TI  - Granulomas of the lips: a rare complication after injection of polylactic acid
      for aesthetic augmentation.

PMID- 17532280
TI  - Periapical cemental dysplasia is common in women with NF1.
AB  - BACKGROUND: Neurofibromatosis type 1 (NF1) is a genetic disorder with skeletal
      involvement. Periapical cemental dysplasia is a rare finding in the normal
      population. METHOD: A total of 55 patients with NF1, 29 female and 26 male
      patients, were evaluated with orthopantomograms, supplemented with periapical
      radiographs if necessary. The vitality of the teeth was measured by two different
      testing methods. RESULTS: A novel finding was the occurrence of cemental
      dysplasia affecting the periapical area of vital mandibular teeth in 8 adult
      women with NF1. Thus, cemental dysplasia was detected in 34.8% of the adult
      female NF1 patients, while cemental dysplasia was not present in men or children
      with NF1. CONCLUSION: Periradicular cemental dysplasia is indeed a new NF1
      related bone lesion type. Our finding suggests that this is the first reported
      sexual dimorphism in the manifestations of NF1. Cemental dysplasia of NF1
      patients should not be confused with periapical findings caused by endodontic
      pathoses. The former do not require active therapy whereas in the latter root
      canal treatment is necessary.

PMID- 17532281
TI  - Alterations in the growth plate associated with growth modulation by sustained
      compression or distraction.
AB  - Sustained mechanical load is known to modulate endochondral growth in the
      immature skeleton, but it is not known what causes this mechanical sensitivity.
      This study aimed to quantify alterations in parameters of growth plate
      performance associated with mechanically altered growth rate. Vertebral and
      proximal tibial growth plates of immature rats and cattle, and rabbit (proximal
      tibia only) were subjected to different magnitudes of sustained loading, which
      altered growth rates by up to 53%. The numbers of proliferative chondrocytes,
      their rate of proliferation, and the amount of chondrocytic enlargement occurring
      in the hypertrophic zone were quantified. It was found that reduced growth rate
      with compression and increased growth rate with distraction were associated with
      corresponding changes in the number of proliferative chondrocytes per unit width
      of growth plate, and in the final (maximum) chondrocytic height in the
      hypertrophic zone (overall correlation coefficients 0.38 and 0.56 respectively).
      According to multiple linear regression coefficients for these two variables
      (0.72 and 1.39 respectively), chondrocytic enlargement made a greater
      contribution to altered growth rates.

PMID- 17532282
TI  - Prenatal ethanol exposure disrupts the histological stages of fetal bone
      development.
AB  - Maternal ethanol intake during pregnancy results in impairments in general growth
      and skeletal development in the offspring. We have previously shown that ethanol
      retards skeletal ossification at doses lower than those that affect growth.
      Moreover, skeletal sites vary in their sensitivity to ethanol effects, with more
      severe effects occurring in bones that undergo a greater proportion of their
      development in utero. Taken together, these data suggest that ethanol has
      specific effects on bone development, and that later stages in the ossification
      process may be particularly affected. Such effects could have important
      implications for the offspring's long-term bone health, as studies suggest that
      the intrauterine environment can program the skeleton. The present study examined
      the histological stages of bone development to determine if prenatal ethanol
      exposure alters the morphological development of the growth plate in the fetal
      rat. Rats were fed a liquid diet containing ethanol (Ethanol, E group), or
      without ethanol (Pair-Fed, PF, or Control, C groups) for 6 weeks: 3 weeks prior
      to breeding and during 3 weeks of pregnancy. Fetal tibiae were fixed, decalcified
      and stained for histological analysis on day 21 of gestation. Maternal ethanol
      intake resulted in a significant decrease in fetal total bone and diaphysis
      lengths, compared with tibiae from PF and C fetuses. Although the lengths of the
      epiphyses were not affected, ethanol disrupted the organization of the
      histological zones within the epiphyses. Prenatal ethanol exposure decreased the
      length of the resting zone, but increased the length of the hypertrophic zone.
      Enlargement of the hypertrophic zone is consistent with an effect of ethanol on
      the later stages of bone development; however, ethanol's effect on the resting
      zone indicates that earlier stages of bone development may also be disrupted. The
      functional significance of these morphological changes to long-term bone health
      remains to be determined.

PMID- 17532283
TI  - Masticatory mechanics of a mandibular distraction osteogenesis site:
      interfragmentary micromovement.
AB  - Micromovement at a fracture or distraction osteogenesis (DO) site may play a
      significant role in bone formation and healing. Mastication is an important
      physiological process that can cause substantial micromovement at a mandibular
      disjunction. The purpose of this study is to characterize and quantify the
      micromovement caused by mastication. Eighteen pigs, divided into three groups
      based on duration of consolidation, received a unilateral (right) mandibular
      angle distraction osteogenesis protocol. Differential variable reluctance
      transducers (DVRTs) and ultrasound crystals were used to measure the change of
      gap width as well as interfragmentary movement during mastication. Synchronized
      chewing video and interfragmentary movement recordings were used to determine the
      magnitude and direction of micromovement at different phases of the chewing
      cycle. The magnitude of micromovement did not increase significantly with
      distraction up to almost 5 mm, but did decrease gradually with consolidation. The
      average micromovement magnitude during the distraction phase was 0.2-0.3 mm,
      equaling 50,000-250,000 microstrain (muepsilon) on interfragmentary tissue. The
      dominant deformation pattern was bending in the sagittal plane. The most common
      direction of bending at the power stroke of chewing was concave dorsally, i.e.,
      superior shortening and inferior lengthening. These findings elucidate how
      masticatory mechanics affect a mandibular distraction site, and the measurements
      may be useful for future simulation studies.

PMID- 17532284
TI  - [Thyroid tuberculosis].
AB  - Thyroid is a rare localization of tuberculosis, and should be considered in the
      diagnosis of nodular lesion of the thyroid gland except for the complicated forms
      with collection in which the fine needle aspiration showed the acid fast bacilli
      on Ziehl-Neelson stain (Koch bacilli) and/or granulomatous inflammation with
      caseation necrosis. We report the case of a 70 year-old woman referred to the
      hospital with a diagnosis of endothoracic goiter without clinical signs of
      tuberculosis. The diagnosis was established after total thyroidectomy and
      histological exam. Six-month treatment with three antituberculous drugs was
      administered with a good outcome.

PMID- 17532287
TI  - [X-linked adrenoleukodystrophy].
AB  - X-linked adrenoleukodystrophy (ALD) is a severe neurodegenerative disorder. ALD
      is characterized by progressive demyelination within the central and peripheral
      nervous system, adrenal insufficiency (Addison's disease) and accumulation of
      very-long-chain fatty acids (VLCFA) in plasma, fibroblasts and tissues. The
      overall incidence of ALD is 1:17,000 including hemizygotes and heterozygotes who
      are frequently symptomatic. There are two main ALD phenotypes: 1) a cerebral
      demyelinating form which affects boys between 5-12 years, but also 35% of adult
      males; 2) a form that mainly involves the spinal cord (adrenomyeloneuropathy,
      AMN) in adult males between 20-50 years and 50% of heterozygous women after the
      age of 40 years. AMN presents with progressive spastic paraparesis. Addison's
      disease may be the first symptom of ALD in boys and adult males. These patients
      are at risk to develop cerebral ALD or AMN for life. ALD results from mutations
      in the ABCD1 gene without correlation between genotype and phenotype. The
      diagnosis of ALD relies upon the measurement of plasma VLCFA levels that allows
      the identification of 100% affected males and of 80-95% heterozygous women.
      Because of these false-negative, it is therefore mandatory to search for a
      mutation in the ABCD1 gene in all women at risk to be heterozygous for ALD. The
      ABCD1 gene encodes a peroxisomal transmembrane protein (ALD protein) with the
      structure of an half ATP-binding cassette transporter. It is possible that ALD
      protein imports VLCFA or VLCFA-CoA into peroxisomes in which they are degraded by
      a peroxisomal beta-oxidation system. Elongation of VLCFAs is enhanced in
      fibroblasts from ALD patients and likely contributes to the load of VLCFA in
      tissues. The underlying mechanisms that lead to cerebral demyelination, axonal
      degeneration in spinal cord and adrenal insufficiency are unknown. The "toxic"
      role of VLCFA accumulation remains to be demonstrated. The mechanisms that lead
      to the inflammatory reaction in cerebral ALD might involve abnormal acylation of
      gangliosides and phospholipids by VLCFA that would result in immune reaction of
      brain macrophages and astrocytes bearing CD1 molecules that recognize lipid
      antigens. De novo mutation of ABCD1 occurs in less than 8% of ALD patients. The
      genetic counseling aims to identify: 1) women who are at risk to be heterozygous;
      2) neurologically asymptomatic boys. It is only at this stage that allogeneic
      bone marrow transplantation has clinical benefit; 3) ALD patients who have
      Addison's disease that can lead to sudden death. Prenatal diagnosis (chorionic
      villus samples, cultured amniotic fluid cells) relies upon DNA based mutation
      detection techniques, expression of ALD protein and measurement of VLCFA levels.
      Allogeneic bone marrow transplantation is the only treatment that provides a
      permanent cure when the procedure is performed at an early stage of cerebral
      demyelination, i.e when the patients are asymptomatic despite abnormal brain MRI.
      Treatment of Addison's disease is mandatory but does not modify the course of
      neurological symptoms. Dietary therapy failed to halt the neurologic progression
      in cerebral ALD and AMN. It might have a partial preventive effect in boys
      treated before 6 years of age.

PMID- 17532288
TI  - Drug treatment of hyperprolactinemia.
AB  - Medical treatment of hyperprolactinemia is based upon use of dopamine agonists
      (DA): bromocriptine, lisuride, quinagolide and cabergoline. In over 80% of cases,
      these drugs induce normal prolactinemia and ovulatory cycles. In resistant cases,
      the DA should be changed. Tolerance may occasionally be poor, particularly with
      bromocriptine, which appears less well-tolerated than quinagolide and than
      cabergoline above all. In the event of intolerance to a given DA, another should
      be tried. In patients with macroprolactinoma treated with DA, MRI monitoring
      should be carried out after 3 months of treatment to verify tumor size reduction,
      then after 1 year, yearly for the next 5 years and once every 5 years if adenoma
      size is stable. In cases of microprolactinoma, control under treatment is
      pointless. MRI may be performed after 1 year and then after 5 years. Once normal
      prolactin levels have been achieved, attempts may be made to stop the treatment.
      When a prolonged treatment is interrupted, especially with cabergoline,
      progressive increase in serum prolactin and return of hyperprolactinemia symptoms
      are seen in only around 20-30% of cases, particularly when residual adenoma
      exists after prolonged treatment. Nevertheless, prolactin levels should continue
      to be monitored after discontinuation of DA, possibly with MRI monitoring, since
      prolactin levels may rise again after a number of months or years. When normal
      prolactin levels have been achieved with DA, another solution consists in
      reducing the dose or dosing frequency of DA in steps to the lowest effective dose
      consistent with maintenance of normal prolactin levels and stable adenoma size.
      For drug-induced hyperprolactinemia, where the causative medication cannot be
      withdrawn, it is often pointless and possibly even dangerous to administer a DA.
      It is therefore necessary to check for absence of pituitary adenoma and where
      necessary, begin treatment with sex steroids so as to ensure satisfactory
      impregnation with sex steroids and avoid osteoporosis. For macroprolactinoma, the
      first-line treatment is drug therapy with DA. At present, there is no evidence to
      suggest that prior treatment with DA can modify the outcome of surgery. With
      microprolactinoma, DA treatment offers a good first-line therapeutic option but
      surgery may also be useful. DAs for microprolactinoma may be withdrawn after
      menopause.

PMID- 17532290
TI  - [Routine medical management of obesity].
AB  - Management of obesity is often reduced to counselling, focusing on factors
      directly affecting energy balance: food intake and physical activity. However,
      the causes of excessive food intake, eating disorders and their causal factors,
      are largely unknown. This can lead to unsuitable obesity management. In the
      present text, we detail the clinical elements which can be helpful for the
      specialist or general practitioner making a global assessment of their overweight
      patients. The goal is to help the patient establish a care project with medical
      support, as would be the case for any chronic disease.

PMID- 17532291
TI  - Odontoblast marker gene expression is enhanced by a CC-chemokine family protein
      MIP-3alpha in human mesenchymal stem cells.
AB  - OBJECTIVE: Macrophage inflammatory protein-3 alpha (MIP-3alpha) is a major CC
      chemokine family protein, which serves as a differentiation factor for
      mesenchymal cells, including osteoblasts and dental pulp cells. The purpose of
      this study was to investigate the influence of MIP-3alpha on human mesenchymal
      stem cell differentiation in vitro. DESIGN: Human mesenchymal stem cells were
      maintained in Dulbecco's modified Eagle's medium in the presence or absence of
      MIP-3alpha and the presence or absence of osteogenic factors (dexamethasone, beta
      glycerophoshate and ascorbic acid). Alkaline phosphatase (ALP) activity was
      measured, and expression of odontoblast and osteoblast markers were examined by
      RT-PCR and Western blotting. RESULTS: MIP-3alpha alone did not increase ALP
      activity, as compared to controls. The combination of MIP-3alpha and osteogenic
      factors increased ALP activity beyond increases observed with osteogenic factors
      alone. mRNA expression of the odontoblast marker dspp was only detectable when
      MIP-3alpha was added together with osteogenic factors at day 7 in three out of
      four samples. DSP protein level was increased only in the samples treated with
      both MIP-3alpha and osteogenic factors until day 5. In contrast, MIP-3alpha did
      not influence levels of the osteoblast markers CBFA1 or BSP. CONCLUSIONS: The
      present study demonstrated that MIP-3alpha enhanced gene expression and protein
      levels of odontoblast-related genes, without affecting levels of the osteogenic
      proteins CBFA1 or BSP.

PMID- 17532292
TI  - Molecular organization of surfactin-phospholipid monolayers: effect of
      phospholipid chain length and polar head.
AB  - Mixed monolayers of the surface-active lipopeptide surfactin-C(15) and various
      lipids differing by their chain length (DMPC, DPPC, DSPC) and polar headgroup
      (DPPC, DPPE, DPPS) were investigated by atomic force microscopy (AFM) in
      combination with molecular modeling (Hypermatrix procedure) and surface pressure
      area isotherms. In the presence of surfactin, AFM topographic images showed phase
      separation for each surfactin-phospholipid system except for surfactin-DMPC,
      which was in good agreement with compression isotherms. On the basis of domain
      shape and line tension theory, we conclude that the miscibility between surfactin
      and phospholipids is higher for shorter chain lengths (DMPC>DPPC>DSPC) and that
      the polar headgroup of phospholipids influences the miscibility of surfactin in
      the order DPPC>DPPE>DPPS. Molecular modeling data show that mixing surfactin and
      DPPC has a destabilizing effect on DPPC monolayer while it has a stabilizing
      effect towards DPPE and DPPS molecular interactions. Our results provide valuable
      information on the activity mechanism of surfactin and may be useful for the
      design of surfactin delivery systems.

PMID- 17532293
TI  - Bi-directional transport of GLUT4 vesicles near the plasma membrane of primary
      rat adipocytes.
AB  - Insulin stimulates glucose uptake into adipocytes by mobilizing intracellular
      membrane vesicles containing GLUT4 proteins to the plasma membrane. Here we
      applied time-lapse total internal reflection fluorescence microscopy to study
      moving parameters and characters of exogenously expressed GLUT4 vesicles in
      basal, insulin and nocodazole treated primary rat adipocytes. Our results showed
      that microtubules were essential for long-range transport of GLUT4 vesicles but
      not obligatory for GLUT4 distribution in rat adipocytes. Insulin reduced the
      mobility of the vesicles, made them tethered/docked to the PM and finally had
      constitutive exocytosis. Moreover, long-range bi-directional movements of GLUT4
      vesicles were visualized for the first time by TIRFM. It is likely that there are
      interactions between insulin signaling and microtubules, to regulating GLUT4
      translocation in rat adipocytes.

PMID- 17532294
TI  - FBXL5 interacts with p150Glued and regulates its ubiquitination.
AB  - The microtubule motor cytoplasmic dynein and its activator dynactin drive
      vesicular transport and mitotic spindle organization. p150(Glued) is the dynactin
      subunit responsible for binding to dynein and microtubules. The F-box proteins
      constitute one of the four subunits of ubiquitin protein ligase complex called
      SCFs (SKP1-cullin-F-box), which governs phosphorylation-dependent ubiquitination
      and subsequent proteolysis. Our recent study showed that the proteolysis of
      mitotic kinesin CENP-E is mediated by SCF via a direct Skp1 link [D. Liu, N.
      Zhang, J. Du, X. Cai, M. Zhu, C. Jin, Z. Dou, C. Feng, Y. Yang, L. Liu, K.
      Takeyasu, W. Xie, X. Yao, Interaction of Skp1 with CENP-E at the midbody is
      essential for cytokinesis, Biochem. Biophys. Res. Commun. 345 (2006) 394-402].
      Here we show that F-box protein FBXL5 interacts with p150(Glued) and orchestrates
      its turnover via ubiquitination. FBXL5 binds to p150(Glued)in vitro and in vivo.
      FBXL5 and p150(Glued) co-localize primarily in the cytoplasm with peri-nuclear
      enrichment in HeLa cells. Overexpression of FBXL5 promotes poly-ubiquitination of
      p150(Glued) and protein turnover of p150(Glued). Our findings provide a potential
      mechanism by which p150(Glued) protein function is regulated by SCFs.

PMID- 17532295
TI  - Role of cardiovascular nitric oxide system in C-type natriuretic peptide effects.
AB  - The aims were to evaluate the role of cardiovascular nitric oxide (NO)-system in
      C-type natriuretic peptide (CNP) actions and to investigate receptor types and
      signaling pathways involved in this interaction. Wistar rats were infused with
      saline or CNP. Mean arterial pressure (MAP) and nitrites and nitrates (NOx)
      excretion were determined. NO synthase (NOS) activity and NOS expression (Western
      blot) were analyzed in atria, ventricle and aorta. CNP decreased MAP and
      increased NOx excretion. CNP estimulated NOS activity, inducing no changes on
      cardiac and vascular endothelial NOS expression. NOS activity induced by CNP was
      abolished by suramin and calmidazoliumand but it is not modified by anantin. CNP
      would interact with NPR-C receptor coupled via G proteins leading to the
      activation Ca(2+)-calmodulin dependent endothelial NOS, increasing NO production
      which would induce the reduction in cardiac myocyte contractility and ANP
      synthesis and secretion in right atria and the relaxation of vascular smooth
      muscle.

PMID- 17532296
TI  - Screening for pharmacological chaperones in Fabry disease.
AB  - As a prerequisite for clinical trials of pharmacological chaperone therapy (PCT)
      for Fabry disease, we developed a rapid screening assay for enhancement of
      endogenous alpha-galactosidase A (alpha-Gal A) in patient-derived cells. We used
      a T-cell based system to screen 11 mutations causing Fabry disease for
      enhanceability using 1-deoxygalactonojirimycin (DGJ). When patient-derived T
      cells were grown in the presence of DGJ, alpha-Gal A activity increased to more
      than 50% of normal in several mutations but was unaffected in others. In addition
      to the mutation R301Q, reported previously, A97V, R112H, R112C, A143T, and L300P
      were enhanceable, but R356W, G132R, A143P, R220X, and 30delG were not. The level
      of alpha-Gal A activity achieved provides a basis for the therapeutic trial of
      DGJ in patients with similarly enhanceable enzyme. This assay method has general
      utility in other disorders in assessing the degree of enhancement of activity of
      mutated proteins by PCT.

PMID- 17532297
TI  - FGF-2 suppresses cellular senescence of human mesenchymal stem cells by down
      regulation of TGF-beta2.
AB  - Human mesenchymal stem cells (hMSCs) are able to both self-replicate and
      differentiate into a variety of cell types. Fibroblast growth factor-2 (FGF-2)
      stimulates the growth of hMSCs in vitro, but its mechanisms have not been
      clarified yet. In this study, we investigated whether cellular senescence was
      involved in the stimulation of hMSCs growth by FGF-2 and the expression levels of
      transforming growth factor-beta1 and -beta2 (TGF-betas). Because hMSCs were
      induced cellular senescence due to long-term culture, FGF-2 decreased the
      percentage of senescent cells and suppressed G1 cell growth arrest through the
      suppression of p21(Cip1), p53, and p16(INK4a) mRNA expression levels.
      Furthermore, the levels of TGF-betas mRNA expression in hMSCs were increased by
      long-term culture, but FGF-2 suppressed the increase of TGF-beta2 mRNA expression
      due to long-term culture. These results suggest that FGF-2 suppresses the hMSCs
      cellular senescence dependent on the length of culture through down-regulation of
      TGF-beta2 expression.

PMID- 17532298
TI  - Fluorescence resonance energy transfer analysis of subunit assembly of the ASIC
      channel.
AB  - Acid-sensing ion channels (ASICs) are believed to be homo- or heteromeric
      complexes, which have been verified by classical methods such as co
      immunoprecipitation or electrophysiological assays. However, the exact subunit
      combinations of ASICs in living cells have not been established yet. Here, we
      apply assays based on fluorescence resonance energy transfer (FRET) between GFP
      color mutants CFP and YFP to investigate ASIC assembly directly in living cells.
      Homomerization as well as heteromerization of different combinations of ASIC
      subunits were found. In addition, our results suggest the formation of
      heteromeric 1a/2a channels of stoichiometry consisting of at least two 1a
      subunits and two 2a subunits. Similar stoichiometry was observed from heteromeric
      1a/2b and 2a/2b channels. Our results imply that these heteromeric ASIC channels
      contain at least four subunits.

PMID- 17532299
TI  - NM23-H2 involves in negative regulation of Diva and Bcl2L10 in apoptosis
      signaling.
AB  - The Bcl-2 family members are evolutionally conserved and crucial regulators of
      apoptosis. Diva (Boo), an ortholog of Bcl2L10 or Bcl-B, is a member of the Bcl-2
      family that has contradictory functions in apoptosis. To understand the signaling
      mechanisms of Diva, we searched for proteins that interact with Diva using the
      yeast two-hybrid system. We identified a nucleoside diphosphate kinase isoform,
      NM23-H2. Here, we show that Diva bound to NM23-H2 in cells in which the
      transmembrane domain of Diva was required, and both proteins were colocalized in
      cytoplasm. Of interest, Diva protein level was significantly down-regulated by
      NM23-H2 as knock down of NM23-H2 restored Diva expression. Overexpression of NM23
      H2 induced apoptosis, and the depletion of NM23-H2 led to the increase of Diva's
      apoptotic activity. Thus, these results indicate the existence of a previously
      undiscovered mechanism by which NM23-H2 involves in the regulation of Diva
      mediated apoptosis.

PMID- 17532300
TI  - NS5A protein of HCV enhances HBV replication and resistance to interferon
      response.
AB  - HCV and HBV are the major causes of chronic liver diseases worldwide. Patients
      with both viruse's co-infection tend to develop severer liver diseases and are at
      high risk of liver-related death. NS5A protein of HCV plays key roles in HCV
      replication and inhibition of host immune responses. In this study, we described
      the establishment of HepG2-derived cell line that stably expresses NS5A protein
      and the application of a cellular system for HBV replication based on a
      recombinant adenovirus carrying HBV genome. Our results demonstrated that NS5A
      enhances the expression of S and E proteins of HBV, as well as the synthesis of
      viral DNA. Moreover, we showed that NS5A assists HBV to escape interferon
      responses. These data suggested that NS5A of HCV may employ multiple strategies
      contributing to the enhancement of HBV replication and interferon resistance
      during the co-infection of HCV and HBV.

PMID- 17532301
TI  - Regulation of alpha- and beta-secretase activity by oxysterols: cerebrosterol
      stimulates processing of APP via the alpha-secretase pathway.
AB  - The cholesterol 24-hydroxylase encoded by the gene CYP46 is expressed almost
      exclusively in central nervous system (CNS) neurons and catalyzes the formation
      of 24S-hydroxycholesterol (24S-OHC) from cholesterol. This conversion corresponds
      to a major pathway for excretion of excess cholesterol from the brain. There is a
      significant flux of another oxysterol, 27-hydroxycholesterol (27-OHC) from the
      circulation into the brain. Polymorphisms within the CYP46A1 gene have been
      associated with Alzheimer's disease (AD) incidence. In this study, we examined
      the effects of 24S-OHC and 27-OHC on the alpha- and beta-secretase activity in
      the human neuroblastoma cell line SH-SY5Y. Furthermore, we examined the effects
      of the two oxysterols on the levels of extra- and intracellular proteins of
      secreted APPalpha (sAPPalpha). Our findings suggest that 24S-OHC may exert a
      unique modulatory effect on APP processing and that this oxysterol increases the
      alpha-secretase activity as well as the alpha/beta-secretase activity ratio. The
      possibility is discussed that the ratio between 24S-OHC and 27-OHC is of
      importance for the generation of amyloid in the brain.

PMID- 17532302
TI  - 15-Deoxy-Delta12,14-prostaglandin J2 (15d-PGJ2) mediates repression of TNF-alpha
      by decreasing levels of acetylated histone H3 and H4 at its promoter.
AB  - Prostaglandin metabolite 15-Deoxy-Delta(12,14)-prostaglandin J2 (15d-PGJ2) is
      known to inhibit a number of pro-inflammatory cytokines as well as being a ligand
      for nuclear receptor PPARgamma. We investigated the ability of 15d-PGJ2 to
      inhibit TNF-alpha gene expression through mechanisms that involve histone
      modification. Pretreatment with 15d-PGJ2 (10 microM) inhibited LPS-stimulated TNF
      alpha mRNA in THP-1 monocytes or PMA-differentiated cells to nearly basal levels.
      A specific PPARgamma ligand, GW1929, failed to inhibit LPS-induced TNF-alpha mRNA
      expression nor did a PPARgamma antagonist, GW9662, alter the repression of TNF
      alpha mRNA in LPS-stimulated cells pretreated with 15d-PGJ2 suggesting a
      PPARgamma-independent inhibition of TNF-alpha mRNA in THP-1 cells. Transfection
      studies with a reporter construct and subsequent treatment with 15d-PGJ2
      demonstrated a dose-dependent inhibition of the TNF-alpha promoter. Additional
      studies demonstrated that inhibition of histone deacetylases with trichostatin A
      (TSA) or overexpression of histone acetyltransferase CBP could overcome 15d-PGJ2
      mediated repression of the TNF-alpha promoter, suggesting that an important
      mechanism whereby 15d-PGJ2 suppresses a cytokine is through factors that regulate
      histone modifications. To examine the endogenous TNF-alpha promoter, chromatin
      immunoprecipitations (ChIP) were performed. ChIP assays demonstrated that LPS
      stimulation induced an increase in histone H3 and H4 acetylation at the TNF-alpha
      promoter, which was reduced in cells pretreated with 15d-PGJ2. These results
      highlight the ability of acetylation and deacetylation factors to affect the TNF
      alpha promoter and demonstrate that an additional important mechanism whereby 15d
      PGJ2 mediates TNF-alpha transcriptional repression by altering levels of
      acetylated histone H3 and H4 at its promoter.

PMID- 17532303
TI  - Genetic polymorphisms of GSTP1 and mEPHX correlate with oxidative stress markers
      and lung function in COPD.
AB  - The genetic susceptibility to COPD might depend on variations in detoxification
      enzymes that activate and detoxify cigarette smoke products, which otherwise
      generate oxidative stress causing pathogenesis. In a case-control study of 202
      COPD patients and 136 normals, we examined the association of polymorphisms
      I105V, A114V of GSTP1 and Y113H, H139R of mEPHX individually or in combination
      with disease and their contribution to oxidative stress markers such as MDA, GSH,
      GPx and airflow obstruction. Patients were over-represented by the alleles 105V,
      114V of GSTP1 and 113H, 139H of mEPHX (chi(2)=10.63, p=0.001, chi(2)=13.92,
      p<0.001, chi(2)=13.02, p<0.001 and chi(2)=4.48, p=0.034, respectively) and the
      haplotypes of same alleles i.e. 105V-114V and 113H-139H (chi(2)=14.58, p<0.001
      and chi(2)=23.14, p<0.001). Moreover, there was marked over-representation of
      combination of genotypes, I105I+A114A of GSTP1 (53% vs. 36%) in controls;
      whereas, the combinations with 105V/114V alleles (64% vs. 47%) of GSTP1 (OR=1.99;
      95% CI=1.28-3.09; p=0.002) and the homozygotes H113H+H139H (27% vs.10%) of mEPHX
      (OR=3.26; 95% CI=1.73-6.15; p=0.0001) in patients. Patients had significantly
      elevated MDA level (p<0.001) and decreased GSH level (p<0.001) and GPx activity
      (p=0.035), respectively. Of note, the genotypes, I105V/V105V, A114V/V114V of
      GSTP1 and Y113H/H113H of mEPHX associated with increased MDA level (p=0.04,
      p=0.03 and p=0.003), decreased GSH level (p=0.019, p=0.007 and p=0.0006) and
      lower FEV1 (p=0.23, p=0.037 and p=0.029), respectively, in patients; so was the
      correlation of these biomarkers and lung function with the combinations of the
      genotypes. In conclusion, 105V/114V alleles of GSTP1 and 113H/139H alleles of
      mEPHX and the combination of genotypes with same alleles associated with
      imbalanced oxidative stress and lung function in patients, signifying the
      importance in the disease.

PMID- 17532304
TI  - Probing the substrate specificity of the ergothioneine transporter with
      methimazole, hercynine, and organic cations.
AB  - Recently, we have identified the ergothioneine (ET) transporter ETT (gene symbol
      SLC22A4). Much interest in human ETT has been generated by case-control studies
      that suggest an association of polymorphisms in the SLC22A4 gene with
      susceptibility to chronic inflammatory diseases. ETT was originally designated a
      multispecific novel organic cation transporter (OCTN1). Here we reinvestigated,
      based on stably transfected 293 cells and with ET as reference substrate, uptake
      of quinidine, verapamil, and pyrilamine. ETT from human robustly catalyzed
      transport of ET (68micfrol/(minmgprotein)), but no transport of organic cations
      was discernible. With ET as substrate, ETT was relatively resistant to inhibition
      by selected drugs; the most potent inhibitor was verapamil (K(i)=11micromol/l).
      The natural compound hercynine and antithyroid drug methimazole are related in
      structure to ET. However, efficiency of ETT-mediated transport of methimazole
      (K(i)=7.5mmol/l) was 130-fold lower, and transport of hercynine (K(i)=1.4mmol/l)
      was 25-fold lower than transport of ET. ETT from mouse, upon expression in 293
      cells, catalyzed high affinity, sodium-driven uptake of ET very similar to ETT
      from human. Additional real-time PCR experiments based on 16 human tissues
      revealed ETT mRNA levels considerably lower than in bone marrow. Our experiments
      establish that ETT is highly specific for its physiological substrate
      ergothioneine. ETT is not a cationic drug transporter, and it does not have high
      affinity for organic cation inhibitors. Detection of ETT mRNA or protein can
      therefore be utilized as a specific molecular marker of intracellular ET
      activity.

PMID- 17532305
TI  - On the basics of carbohydrate-metal chemistry: complexes of palladium(II) with
      hydroxyaldehyde and -ketone hydrates.
AB  - In this work, we present novel complexes of hydroxyaldehydes and ketones with
      palladium(II). The compounds are studied by two-dimensional NMR spectroscopy in
      solution (COSY, HMQC, HMBC). Glycolaldehyde, d-glyceraldehyde, glyoxal and 2,4-O
      ethylidene-d-erythrose were used as aldehydes, d-erythrulose was used as an alpha
      hydroxyketone. Although different species are present in solution, only the
      hydrated forms of the aldehydes can coordinate to the metal centre. These
      complexes are stable at 4 degrees C in aqueous solution. The crystal structure of
      a complex formed by mesoxalic acid and palladium(II) is reported and shows
      coordination by both hydroxy groups of the hydrated ketone.

PMID- 17532306
TI  - High-performance liquid chromatography/electrospray ionization ion-trap mass
      spectrometry for analysis of oligosaccharides derivatized by reductive amination
      and N,N-dimethylation.
AB  - Milk oligosaccharides derivatized by reductive amination with benzylamine
      followed by N,N-dimethylation (DMBA-oligosaccharides), were analyzed by high
      performance liquid chromatography/electrospray ionization ion-trap mass
      spectrometry (HPLC/ESI-ITMS). Separation of DMBA-oligosaccharides was achieved on
      a graphitized carbon column eluted with aqueous acetonitrile and the DMBA
      oligosaccharides were detected by positive-ion mode ESI-ITMS allowing sample
      amounts down to approximately 30fmol of single DMBA-oligosaccharides injected on
      the HPLC column. MS/MS operation of the mass spectrometer resulted in the
      detection of diagnostic fragments, mainly belonging to the Y-series, allowing
      differentiation between isomeric milk oligosaccharides. HPLC/ESI-ITMS/MS/MS
      experiments indicated the migration of fucose residues of the DMBA milk
      oligosaccharides to the modified reducing end glucose residue during analysis, a
      migration previously only observed for proton adduct ions.

PMID- 17532307
TI  - Enzymatic synthesis of dTDP-4-amino-4,6-dideoxy-D-glucose using GerB (dTDP-4-keto
      6-deoxy-D-glucose aminotransferase).
AB  - Over-expressed GerB (dTDP-4-keto-6-deoxy-d-glucose aminotransferase) of
      Streptomyces sp. GERI-155 was used in the enzymatic synthesis of dTDP-4-amino-4,6
      dideoxy-D-glucose (2) from dTDP-4-keto-6-deoxy-D-glucose (1). [Carbohydrate
      structure: see text]. Five enzymes including dTMP kinase (TMK), acetate kinase
      (ACK), dTDP-glucose synthase (TGS), dTDP-glucose 4,6-dehydratase (DH), and dTDP-4
      keto-6-deoxy-d-glucose aminotransferase (GerB) were used to synthesize 2 on a
      large scale from glucose-1-phosphate and TMP. A conversion yield of up to 57% was
      obtained by HPLC peak integration given a reaction time of 270min. After
      purification by two successive preparative HPLC systems, the final product was
      identified by HPLC and then analyzed by (1)H, (13)C, (1)H-(1)H COSY NMR
      spectrometry.

PMID- 17532308
TI  - Paraoxonase (PON1) polymorphism and activity as the determinants of sensitivity
      to organophosphates in human subjects.
AB  - Paraoxonase (PON1) plays an important role in mechanism of organophosphorus
      compound (OP) toxicity, as seen both in vitro and in vivo studies. Polymorphisms
      of PON1 gene at coding and promoter regions have also been to affect on the
      hydrolytic activity and PON1 level. The objectives of this study were to
      determine PON1 polymorphism and activity in an OP-exposed population and the
      effects on inhibition of cholinesterase activity. The studied population
      consisted of control (n=30) and exposed groups (n=90). All enzyme activities
      (AChE, BuChE, paraoxonase, arylesterase and diazonase) were measured once for
      control group and two periods of exposure for exposed group. Three polymorphisms
      of PON1 (Q192R, L55M and T-108C) were identified only in the exposed subjects.
      The results demonstrated that AChE activity in both high (345.5 microkat/gHb) and
      low exposure periods (496.9 microkat/gHb) of the exposed group were significantly
      different from control group (649.7 microkat/gHb, p<0.01). For BuChE activity,
      the exposed group also showed the statistically lower level in both periods (high
      exposure period: 62.17 microkat/L and low exposure period: 81.84 microkat/L) than
      those in the control group (93.35 microkat/L). Serum paraoxonase activity was
      significantly different among individual genotypes, RR>QR>RR, LL>LM and -108CC>
      108CT>-108TT, but this was not found for those of arylesterase and diazonase
      activities. Q192R and L55M as well as Q192R and T-108C also presented substantial
      linkage disequilibrium. Further analysis was performed with haplotypes and
      various enzyme activities. AChE activity was not affected by haplotypes.
      Individuals with "211" haplotype showed significantly higher paraoxonase activity
      and BuChE activity than other haplotypes but not in diazonase activity. In
      conclusion, PON1 gene exhibited a wide variation in enzyme activities both within
      and between genotypes which implied insights of a potentially difference in
      sensitivity to OP toxicity.

PMID- 17532309
TI  - Biological availability of selenosugars in rats.
AB  - The biological availability and metabolism of two selenosugars orally
      administered to rats were investigated. Two other selenium species, selenite and
      trimethylselenonium ion (TMSe) were included in the study as positive and
      negative controls, respectively. Male Wistar strain rats (three per group) at 8
      weeks of age were exposed to sodium selenite, TMSe, selenosugar 1 (methyl-2
      acetamido-2-deoxy-1-seleno-beta-D-galactopyranoside) or selenosugar 2 (methyl-2
      acetamido-2-deoxy-1-seleno-beta-D-glucopyranoside) through drinking water for 48
      h. Total selenium concentrations (ICPMS) and selenium species concentrations
      (HPLC/ICPMS) were determined in urine samples collected in two 24h periods during
      the exposure, and total selenium concentrations in liver, kidney, small intestine
      and blood were determined at the end of the experiment. The major species found
      in background urine were selenosugar 1 (major metabolite) and TMSe (minor
      metabolite). Rats exposed to selenite excreted large quantities of selenosugars
      and TMSe consistent with efficient uptake and biotransformation of selenite,
      whereas TMSe-exposed rats excreted large quantities of TMSe, but there was no
      significant increase of other selenium metabolites, consistent with TMSe being
      taken up and excreted unchanged. Rats exposed to selenosugars, however, excreted
      significant quantities of TMSe suggesting that the sugars were at least partly
      biologically available and biotransformed. Rats exposed to selenite accumulated
      selenium in the liver, kidney, small intestine and blood, whereas no accumulation
      was observed for the other samples except for small increases in selenium
      concentrations of small intestine from the two selenosugar-exposed groups.

PMID- 17532310
TI  - Application of mitochondrial genome information in cancer epidemiology.
AB  - Two genomes, nuclear and mitochondrial, exist in humans although information
      contained in the mitochondrial genome has not been fully utilized in cancer
      epidemiology. Over the last few years, a variety of approaches have been
      developed to improve results of conventional cancer screening by detecting
      molecular markers in different populations. Mitochondrial DNA alterations
      (mutations, deletions and instability) are emerging as new molecular markers for
      detecting a variety of cancers in tissue samples and biofluids which can be
      included in population screening studies. Since mitochondrial genome is small
      (16.6 kb) and high-throughput assays have been developed for sequencing whole
      mitochondrial genome, it can be adopted by most of the laboratories conducting
      epidemiological studies. Applications of mitochondrial DNA markers to identify
      high risk populations and future challenges are discussed in this article.

PMID- 17532311
TI  - A rapid and sensitive immunoresonance scattering spectral assay for microalbumin.
AB  - BACKGROUND: Microalbuminuria (MAU) is the earliest clinical finding for renal
      disease and a risk factor for hypertensive cardiovascular disease. Several
      methods, including enzyme-linked immunosorbent assay (ELISA), radioimmunoassay
      (RIA), immunoturbidimetry (IT), immunonephelometry (IN), chemiluminescence
      immunoassay (CLIA), fluorescence immunoassay (FIA) and time-resolved fluorescence
      (TRF) have been applied for detection of MAU. However, the resonance scattering
      (RS) spectral assay, based on the immunoreaction and its resonance scattering
      effect, has not been reported. METHOD: In the presence of 75 mg/l polyethylene
      glycol (PEG), the immunoreaction of microalbumin (Malb) and its goat anti-human
      Malb antibody took place specifically in pH 4.4 buffer solution and aggregated to
      form immunocomplex particles that exhibit a strongest resonance scattering peak
      at 488 nm, and it was used to assay of Malb. RESULTS: The RS intensity at 488 nm
      (DeltaI) was proportional to the Malb concentration (C) in the range of 0.03-0.96
      mg/l, the regression equation was DeltaI=116.0C-2.1, the detection limit was 0.02
      mg/l. Urine samples from 20 healthy subjects were assayed by this assay. The
      results were in agreement with those obtained with IT. CONCLUSION: This assay has
      been applied to detection of Malb in real samples, with simplicity, rapidity,
      high sensitivity and good selectivity.

PMID- 17532312
TI  - Relationship between apolipoproteins and the alteration of HDL subclasses in
      hyperlipidemic subjects.
AB  - BACKGROUND: To elucidate the relationship between the apolipoproteins, especially
      apoA-I and the alteration of HDL subclasses in hyperlipidemic, HTC and HTG
      subjects. METHODS: ApoA-I contents of plasma HDL subclasses were quantitated by
      two-dimensional gel electrophoresis coupled with immunodetection in 233
      normolipidemic subjects and 312 hyperlipidemic subjects (132 HTC and 180 HTG
      subjects). Making use of the mean +/-1 SD of apoA-I levels, we further subdivided
      normolipidemic, hyperlipidemic, HTC and HTG subjects into 3 subgroups,
      respectively. RESULTS: Subjects in the middle and low apoA-I subgroups had
      decreased HDL-C and apoA-I while increased TG, apoB100, apoCII, apoCIII and apoE
      concentrations. With the reduction of apoA-I concentrations, the apoA-I contents
      of all HDL subclasses decreased successively and significantly. The relative
      percentage of small-sized HDL increased significantly while those of large-sized
      HDL(2a), HDL(2b) decreased significantly in hyperlipidemic, especially in HTG
      group. Multiple liner regression result revealed that apoA-I was positively and
      significantly correlated with all HDL subclasses and apoA-I level influenced the
      distribution of HDL subclasses powerfully in hyperlipidemic subjects.
      CONCLUSIONS: Both the rate and efficiency of RCT might be weakened more seriously
      in hyperlipidemic, especially in HTG subjects with low apoA-I levels. ApoA-I
      level might be a powerful factor correlated with the distributions of HDL
      subclasses.

PMID- 17532313
TI  - Relations between homocysteine, folate and vitamin B12 in vascular dementia and
      in Alzheimer disease.
AB  - OBJECTIVES: The aim of this study was to evaluate the relationship between
      homocysteine (Hcy), folate and vitamin B12 levels in vascular dementia (VaD) and
      Alzheimer Disease (AD) to elucidate if they had similar pathogenesis due to
      cerebrovascular injury. DESIGN AND METHODS: Plasma Hcy and serum folate, vitamin
      B12 levels were studied 67 VaD, 51 AD and 40 healthy control subjects. Vascular
      risk factors in these groups were also considered. RESULTS: The changes in the
      levels of Hcy, folate and vitamin B12 were found to be not related with vascular
      risk factors. In VaD, Hcy level was higher (p<0.001), folate and vitamin B12
      levels were lower (p<0.05 for folate, p<0.001 for vitamin B12) than those in AD.
      Hcy level was negatively correlated with folate and vitamin B12 (p<0.05) in VaD
      but in AD. Hcy/folate and Hcy/vitamin B12 ratios were the highest in VaD.
      CONCLUSION: The increase of Hcy in AD were seemed to be not related to
      cerebrovascular injury. It is possibly related to biochemical damages as result
      of oxidative stress.

PMID- 17532314
TI  - The effect of alpha-Tocopherol supplementation on training-induced elevation of
      S100B protein in sera of basketball players.
AB  - OBJECTIVE: To investigate the effect of alpha-Tocopherol (alpha-T)
      supplementation on S100B elevated serum levels in basketball players' training.
      DESIGN: Blood was obtained from 10 basketball players pre-exercise (group A),
      post-exercise (group B) and after 30 days on alpha-T (200 mg/24 h orally)
      supplementation pre- (group C) and post-training (group D). Blood samples were
      taken for the evaluation of total antioxidant status (TAS), alpha-T and
      catecholamines in plasma and S100B and muscle enzyme levels in serum. METHODS:
      TAS, muscle enzymes: creatine kinase (CK), lactate dehydrogenase (LDH), and S100B
      protein levels were measured with commercial kits, whereas alpha-T and
      catecholamine levels with HPLC methods. RESULTS: TAS was found higher in the
      groups with alpha-T addition (groups C and D) than in the other ones. On the
      contrary, CK, LDH and S100B were remarkably lower (116.8+9.5 U/L, 427+22 U/L,
      0.18+0.04 microg/L, respectively) in group D than those in group B (286+12 U/L,
      688+26 U/L, 0.28+0.06 microg/L, p<0.001, respectively). S100B levels were
      negatively correlated with TAS (r=-0.64, p<0.001) and positively with CK levels
      (r=0.58, p<0.001). CONCLUSIONS: alpha-T supplementation may reduce S100B
      increased release from muscle and nerves induced by training. S100B serum
      evaluation may be a useful biomarker for the effect of training on the
      participation of the neuromuscular system.

PMID- 17532315
TI  - Perceptual adaptation to non-native speech.
AB  - This study investigated talker-dependent and talker-independent perceptual
      adaptation to foreign-accent English. Experiment 1 investigated talker-dependent
      adaptation by comparing native English listeners' recognition accuracy for
      Chinese-accented English across single and multiple talker presentation
      conditions. Results showed that the native listeners adapted to the foreign
      accented speech over the course of the single talker presentation condition with
      some variation in the rate and extent of this adaptation depending on the
      baseline sentence intelligibility of the foreign-accented talker. Experiment 2
      investigated talker-independent perceptual adaptation to Chinese-accented English
      by exposing native English listeners to Chinese-accented English and then testing
      their perception of English produced by a novel Chinese-accented talker. Results
      showed that, if exposed to multiple talkers of Chinese-accented English during
      training, native English listeners could achieve talker-independent adaptation to
      Chinese-accented English. Taken together, these findings provide evidence for
      highly flexible speech perception processes that can adapt to speech that
      deviates substantially from the pronunciation norms in the native talker
      community along multiple acoustic-phonetic dimensions.

PMID- 17532316
TI  - Essential roles of mesenchyme-derived beta-catenin in mouse Mullerian duct
      morphogenesis.
AB  - Members of the Wnt family of genes such as Wnt4, Wnt5a, and Wnt7a have been
      implicated in the formation and morphogenesis of the Mullerian duct into various
      parts of the female reproductive tract. These WNT ligands elicit their action via
      either the canonical WNT/beta-catenin or the non-canonical WNT/calcium pathway
      and could possibly function redundantly in Mullerian duct differentiation. By
      using the Mullerian duct-specific anti-Mullerian hormone receptor 2 cre (Amhr2
      cre) mouse line, we established a conditional knockout model that removed beta
      catenin specifically in the mesenchyme of the Mullerian duct. At birth, loss of
      beta-catenin in the Mullerian duct mesenchyme disrupted the normal coiling of the
      oviduct in the knockout embryo, resembling the phenotype of the Wnt7a knockout.
      The overall development of the female reproductive tract was stunted at birth
      with a decrease in proliferation in the mesenchyme and epithelium. We also
      discovered that Wnt5a and Wnt7a expression remained normal, excluding the
      possibility that the phenotypes resulted from a loss of these WNT ligands. We
      examined the expression of Frizzled (Fzd), the receptors for WNT, and found that
      Fzd1 is one receptor present in the Mullerian duct mesenchyme and could be the
      putative receptor for beta-catenin activation in the Mullerian duct. In summary,
      our findings suggest that mesenchymal beta-catenin is a downstream effector of
      Wnt7a that mediates the patterning of the oviduct and proper differentiation of
      the uterus.

PMID- 17532317
TI  - Maternal pregnancy serum level of heptachlor epoxide, hexachlorobenzene, and beta
      hexachlorocyclohexane and risk of cryptorchidism in offspring.
AB  - Prenatal exposure to environmental endocrine disrupters has been postulated to
      cause adverse effects on male reproductive health. Exposure to organochlorine
      pesticides with anti-androgenic and estrogenic potency has been shown to
      interfere with the sex-hormone-dependent process of testicular descent in animal
      models. We examined the relation between serum levels of the pesticides
      heptachlor epoxide (HCE), hexachlorobenzene (HCB), and beta-hexachlorocyclohexane
      (beta-HCCH) in pregnant women, and the occurrence of cryptorchidism in their
      sons. These three pesticides were previously suggested as risk factors for
      cryptorchidism. In a nested case-control design, we compared serum levels between
      mothers of cases (n = 219) and controls (n = 564), selected from the
      Collaborative Perinatal Project, a US birth cohort study of pregnancies in 1959
      1966. The offspring of mothers with HCE levels above the 90th percentile compared
      to those below the 10th percentile had an adjusted odds ratio of cryptorchidism
      of 1.2 (95% confidence interval 0.6-2.6); for beta-HCCH the odds ratio was 1.6
      (0.7-3.6). For HCB the adjusted odds ratio was near one. These results provide
      little support for an association of cryptorchidism with exposure to low levels
      of HCE or HCB. For beta-HCCH the findings were somewhat suggestive of an
      association but were inconclusive.

PMID- 17532318
TI  - Cellular magnesium acquisition: an anomaly in embryonic cation homeostasis.
AB  - The intracellular dominance of magnesium ion makes clinical assessment difficult
      despite the critical role of Mg(++) in many key functions of cells and enzymes.
      There is general consensus that serum Mg(++) levels are not representative of the
      growing number of conditions for which magnesium is known to be important. There
      is no consensus method or sample source for testing for clinical purposes. High
      intracellular Mg(++) in vertebrate embryos results in part from interactions of
      cations which influence cell membrane transport systems. These are functionally
      competent from the earliest stages, at least transiently held over from the
      unfertilized ovum. Kinetic studies with radiotracer cations, osmolar variations,
      media lacking one or more of the four biological cations, Na(+), Mg(++), K(+),
      and Ca(++), and metabolic poison 0.05 mEq/L NaF, demonstrated that: (1) all four
      cations influence the behavior of the others, and (2) energy is required for
      uptake and efflux on different time scales, some against gradient. Na(+) uptake
      is energy dependent against an efflux gradient. The rate of K(+) loss is equal
      with or without fluoride, suggesting a lack of an energy requirement at these
      stages. Ca(++) efflux took twice as long in the presence of fluoride, likely due
      in part to intracellular binding. Mg(++) is anomalous in that early teleost
      vertebrate embryos have an intracellular content exceeding the surrounding sea
      water, an isolated unaffected yolk compartment, and a clear requirement for
      energy for both uptake and efflux. The physiological, pathological, and
      therapeutic roles of magnesium are poorly understood. This will change: (1) when
      (28)Mg is once again generally available at a reasonable cost for both basic
      research and clinical assessment, and (2) when serum or plasma levels are
      determined simultaneously with intracellular values, preferably as part of
      complete four cation profiles. Atomic absorption spectrophotometry, energy
      dispersive x-ray analysis, and inductively coupled plasma emission spectroscopy
      on sublingual mucosal and peripheral blood samples are potential methods of value
      for coordinated assessments.

PMID- 17532319
TI  - Coupled positive feedbacks provoke slow induction plus fast switching in
      apoptosis.
AB  - Apoptosis is a form of a programmed cell death for multicellular organisms to
      remove unwanted or damaged cells. This critical choice of cellular fate is an all
      or-none process, but its dynamics remains unraveled. The switch-like apoptotic
      decision has to be reliable, and once a pro-apoptotic fate is determined it
      requires fast and irreversible execution. One of the key regulators in apoptosis
      is caspase-3. Interestingly, activated caspase-3 quickly executes apoptosis, but
      it takes considerable time to activate it. Here, we have analyzed this "slow
      induction plus fast switching" mechanism of caspase-3 through mathematical
      modeling and computational simulation. First, we have shown that two positive
      feedbacks, composed of caspase-8 and XIAP, are essential for the "slow induction
      plus fast switching" behavior of caspase-3. Second, we have found that XIAP in
      the feedback loops primarily regulates induction time of caspase-3. In many
      cancer cells activation of caspase-3 is suppressed. Our results suggest that
      reinforcement of the positive feedback by XIAP, which relieves XIAP-mediated
      caspase-3 inhibition, might favor a pro-apoptotic cellular fate.

PMID- 17532320
TI  - Debridement and wound closure of open fractures: the impact of the time factor on
      infection rates.
AB  - Open fracture management represents an orthopaedic emergency. Early aggressive
      management of these debilitating injuries within the first 6h has been encouraged
      in order to minimise the risk of infection and long term sequelae. Debridement
      and wash-out of the wound, followed by stabilisation of the bony elements and
      closure of the soft-tissue envelope are all considered essential. However, the
      available scientific evidence supporting the timing of this multistage approach
      of open fracture management, and the "Six-hour rule" itself, are unclear. This
      review article analyses the available evidence regarding the impact of the timing
      of wound debridement and closure of open fractures of the lower extremity.

PMID- 17532321
TI  - Prurigo pigmentosa in a pregnant woman.

PMID- 17532323
TI  - Magnetic targeting of mechanosensors in bone cells for tissue engineering
      applications.
AB  - Mechanical signalling plays a pivotal role in maintaining bone cell function and
      remodelling of the skeleton. Our previous work has highlighted the potential role
      of mechano-induction in tissue engineering applications. In particular, we have
      highlighted the potential for using magnetic particle techniques for tissue
      engineering applications. Previous studies have shown that manipulation of
      integrin attached magnetic particles leads to changes in intracellular calcium
      signalling within osteoblasts. However, due to the phenomenon of particle
      internalisation, previous studies have typically focused on short-term
      stimulation experiments performed within 1-2 h of particle attachment. For tissue
      engineering applications, bone tissue growth occurs over a period of 3-5 weeks.
      To date, no study has investigated the cellular responses elicited from
      osteoblasts over time following stimulation with internalised magnetic particles.
      Here, we demonstrate the long-term biocompatibility of 4.5 microm RGD-coated
      particles with osteoblasts up to 21 days in culture, and detail a time course of
      responses elicited from osteoblasts following mechanical stimulation with
      integrin attached magnetic particles (<2h post attachment) and internalised
      particles (>48h post attachment). Mechanical manipulation of both integrin
      attached and internalised particles were found to induce intracellular calcium
      signalling. It is concluded that magnetic particles offer a tool for applying
      controlled mechanical forces to osteoblasts, and can be used to stimulate
      intracellular calcium signalling over prolonged periods of time. Magnetic
      particle technology presents a potentially valuable tool for tissue engineering
      which permits the delivery of highly localised mechano-inductive forces directly
      to cells.

PMID- 17532322
TI  - Comparison of subclinical coronary atherosclerosis and risk factors in unselected
      populations in Germany and US-America.
AB  - BACKGROUND: On the basis of the Framingham risk algorithm, overestimation of
      clinical events has been reported in some European populations. Electron-beam
      computed tomography-derived quantification of coronary artery calcification (CAC)
      allows for non-invasive assessment of coronary atherosclerosis in the general
      population and may thus add important in vivo information on the path from risk
      factor exposure to formation of clinical events. The current study was undertaken
      to compare the relationship between risk factors and subclinical coronary
      atherosclerosis between non-Hispanic white cohorts in Germany and US-America, the
      hypothesis being that subclinical coronary atherosclerosis might be less
      prevalent in Europe at the same level of classical risk factor exposure. METHODS:
      The Heinz Nixdorf Recall (HNR) study, conducted in the German Ruhr area and the
      Epidemiology of Coronary Calcification (ECAC) study, conducted in Olmsted County,
      Minnesota, both recruited large unselected cohorts, men and women aged 45-74
      years, from the general population. All subjects with no history of coronary
      artery disease (CAD) or stroke were included (n=3120 in HNR, n=703 in ECAC).
      Coronary risk factors were assessed by personal and computer-assisted interviews
      and direct laboratory measurements. Cardiovascular medication use
      (antihypertensive, lipid-lowering, and anti-diabetic) was noted. CAC scores were
      determined using the Agatston method in an identical fashion in both studies.
      RESULTS: Adverse levels of risk factors were more prevalent, and the Framingham
      risk score was higher (10.6+/-7.6 versus 9.3+/-7.1, p<0.001) in HNR than ECAC,
      respectively. There was no difference in body mass index (BMI). CAC scores were
      greater in HNR than in ECAC (mean values, 155.7+/-423.0 versus 107.2+/-280.0;
      median values, 11.9 versus 2.4; p<0.001, respectively). When subjects were
      matched on CAD risk factors, presence and quantity of CAC were similar in the 2
      cohorts. Risk factors significantly associated with CAC score in both studies
      included: age, male sex, current and former smoking, systolic blood pressure, and
      non-HDL-cholesterol. Inferences were similar after excluding subjects using lipid
      or blood pressure-lowering medications. Using the same risk factor variables for
      modelling, the predicted CAC scores were comparable in both cohorts. CONCLUSIONS:
      In the higher-risk German cohort, presence and quantity of CAC were greater than
      in the lower-risk US-American cohort. Risk factor associations with CAC were very
      similar in both unselected populations. We could not demonstrate a relative
      increase in subclinical coronary atherosclerosis in the US-American cohort. It
      appears possible to compare CAC as a measure of subclinical coronary artery
      disease in different populations on different continents, and accordingly,
      scanning guidelines might be translated across these populations.

PMID- 17532324
TI  - Determination of conjugated linoleic acid in human plasma by fast gas
      chromatography.
AB  - A new method for the determination of the main isomers of conjugated linoleic
      acid (CLA) in human and animal plasma was developed by gas chromatography coupled
      to flame ionization detection (GC-FID). The new method introduces three main
      advantages in comparison to the current available methodologies: firstly it does
      not require previous lipid extraction, secondly the chromatographic separation of
      CLA isomers was performed on an Rtx-2330 column significantly shorter and thinner
      than the typical long highly polar capillary columns in use that allows a faster
      analysis than in current methodologies, and thirdly the amount of sample needed
      to perform the analyses was substantially lower than the amount used in current
      routine methodologies. Its application to human plasma and rat plasma showed to
      be robust and reliable for quick and correct identification of the main CLA
      isomers in particular, and the total fatty acid profile in general, in routine
      analysis.

PMID- 17532325
TI  - Simple, rapid, and sensitive liquid chromatography-fluorescence method for the
      quantification of tranexamic acid in blood.
AB  - Tranexamic acid (TA) is a synthetic antifibrinolytic agent that is being
      considered as a candidate adjuvant drug for site-specific pharmaco-laser therapy
      of port wine stains. For drug utility studies, a high-performance liquid
      chromatography (HPLC)-fluorescence method was developed for the quantification of
      TA in blood. Platelet-poor plasma was prepared, size-separated using 3kDa cut-off
      centrifuge filters, and derivatized with naphthalene-2-3-dicarboxaldehyde (NDA)
      and cyanide. The excess of NDA was quenched after 2 min by adding tryptophan. The
      derivatives were separated on a 2.1mm C18 column using an acetate
      buffer/acetonitrile gradient. Excellent separation from plasma background was
      obtained at pH 5.5. Quantification was carried out at 440/520 nm. The limit of
      detection was 0.5 microM and the mean+/-SD recovery from whole blood was 81.7+/
      10.9%. Derivatized TA samples were stable for at least 36 h at 4 degrees C. The
      method was successfully applied to a heat-induced TA release study from
      thermosensitive liposomes.

PMID- 17532326
TI  - Electrokinetic studies of metal oxides in the presence of alkali
      trichloroacetates, trifluoroacetates, and trifluoromethanesulfonates.
AB  - The electrokinetic potentials of anatase (titanium dioxide) and alpha-alumina
      were studied by means of various instruments in the presence of sodium and
      potassium trichloroacetates, trifluoroacetates, and trifluoromethanesulfonates at
      various pH, ionic strengths, and solid-to-liquid ratios. At concentrations up to
      0.01 M, these salts do not induce substantial shifts in the isoelectric point of
      the oxides. Such behavior is typical of inert electrolytes.

PMID- 17532327
TI  - Hydroxyl functionalized thermosensitive microgels with quadratic crosslinking
      density distribution.
AB  - N-isopropylacrylamide (NIPA) based uniform thermosensitive microgels were
      synthesized by dispersion polymerization by using relatively hydrophilic
      crosslinking agents with hydroxyl functionality. Glycerol dimethacrylate (GDMA),
      pentaerythritol triacrylate (PETA) and pentaerythritol propoxylate triacrylate
      (PEPTA) were used as crosslinking agents with different hydrophilicities. A
      protocol was first proposed to determine the crosslinking density distribution in
      the thermosensitive microgel particles by confocal laser scanning microscopy
      (CLSM). The microgels were fluorescently labeled by using hydroxyl group of the
      crosslinking agent. The CLSM observations performed with the microgels
      synthesized by three different crosslinking agents showed that the crosslinking
      density exhibited a quadratic decrease with the increasing radial distance in the
      spherical microgel particles. This structure led to the formation of more loose
      gel structure on the particle surface with respect to the center. Then the use of
      hydrophilic crosslinking agents in the dispersion polymerization of NIPA made
      possible the synthesis of thermosensitive microgels carrying long, flexible and
      chemically derivatizable (i.e., hydroxyl functionalized) fringes on the surface
      by a single-stage dispersion polymerization. The microgels with all crosslinking
      agents exhibited volume phase transition with the increasing temperature. The
      microgel obtained by the most hydrophilic crosslinking agent, GDMA exhibited
      higher hydrodynamic diameters in the fully swollen form at low temperatures than
      those obtained by PETA and PEPTA. Higher hydrodynamic size decrease from fully
      swollen form to the fully shrunken form was also observed with the same microgel.

PMID- 17532328
TI  - Adsorption behavior of DODAB/DPPC vesicles on silica.
AB  - The interaction between composite dipalmitoylphosphatidylcholine
      (DPPC)/dioctadecyldimethylammonium bromide (DODAB) bilayer vesicles in the gel
      state and silica is investigated over the 0-20% DODAB range from determination of
      adsorption curves, silica sedimentation, particle sizing and zeta-potentials. At
      1 mg/mL silica, 0% DODAB, pH 6.3, over the 0-150 mM NaCl range of ionic
      strengths, high affinity adsorption curves were barely affected by ionic strength
      and all of them exhibited limiting adsorption values above the level expected for
      single bilayer deposition. At 1 mg/mL silica, 2% DODAB, pH 6.3 and 1 mM NaCl,
      high affinity adsorption curves fortuitously presented limiting adsorption
      indicative of one bilayer deposition on each silica particle. At %DODAB<2% or
      %DODAB>2%, limiting adsorption was above and below the level expected for bilayer
      deposition, respectively. Increasing %DODAB in the vesicle composition negatively
      modulated the limiting adsorption on silica despite the increasing surface charge
      on vesicles and electrostatic attraction between vesicles and particles. The
      results point out the difficulty of closed vesicle disruption (required for
      bilayer deposition from vesicles) when the bilayer is tightly packed in the rigid
      gel state and might be of interest for analytical applications of immobilized
      vesicles on silica.

PMID- 17532329
TI  - Computer simulation of adsorption kinetics of surfactants on solid surfaces.
AB  - Adsorption kinetics of surfactants on solid surfaces has been studied by using
      computer simulation. Both bulk surfactant concentration and diffusion region are
      explicitly integrated in our model. Depending on the head-surface interaction,
      our simulation results indicate that there exist two different kinetic modes in
      adsorption process of surfactants on solid surfaces. One is the four-regime mode
      and the other is step-wise mode. For the strongly attractive head-surface
      interaction, four distinct regimes of surfactant adsorption are found: a
      diffusion-controlled regime, a self-assembly controlled regime, an intermediate
      coverage regime and a saturated regime. In particular, the adsorption in second
      regime displays a power-law time dependence with an exponent unrelated to bulk
      concentrations and diffusion coefficients. While for the weaker adsorption
      surfaces, the step-wise mode is found. The mode includes a low-coverage
      nucleation regime and the saturated regime after a sudden aggregation of
      surfactants on the substrates which occurs stochastically. Besides the head
      surface interaction, in this work, the effects of surfactant diffusivity, bulk
      concentration, the length of diffusion zone and surfactant architecture on the
      adsorption kinetics are also considered. The simulated adsorption kinetics is
      compared qualitatively with experimental results.

PMID- 17532330
TI  - Self-assembly, hydration, and structures in N-decanoyl-N-methylglucamide aqueous
      solutions: effect of salt addition and temperature.
AB  - The influence of NaCl addition and temperature on the self-assembly, hydration,
      and structures of N-decanoyl-N-methylglucamide (MEGA-10) in dilute solution has
      been investigated by using several experimental techniques, including
      tensiometry, steady-state fluorescence, density, viscosity, and static and
      dynamic light scattering. Tensiometry and fluorescence probe studies, by using
      pyrene as a probe, were used to obtain the critical micelle concentration (cmc)
      upon the electrolyte addition. The mean micellar aggregation numbers (N(agg)) as
      a function of the salt addition were obtained by both static light scattering and
      static quenching methods. The N(agg) values estimated by both methods were found
      to be in good agreement. It was found that the increase in the micelle size,
      produced by the addition of NaCl, is due to the increase in the aggregation
      number and in the amount of water non-specifically associated to the micelle. On
      the other hand, we have observed that the aggregation number remains invariant in
      the temperature range studied, whereas the hydrodynamic radius slightly
      decreases. The effect of electrolyte addition and temperature on the properties
      of MEGA-10 micelles is much less pronounced than those observed in the
      traditionally used POE-based surfactants.

PMID- 17532331
TI  - Preparation, characterization, and Zn(2+) adsorption behavior of chemically
      modified MCM-41 with 5-mercapto-1-methyltetrazole.
AB  - A mesoporous silica (MCM-41) has been chemically modified with 5-mercapto-1
      methyltetrazole using the homogeneous route. This synthetic route involved the
      reaction of 5-mercapto-1-methyltetrazole with 3-chloropropyltriethoxysilane prior
      to immobilization on the support. The resulting material (MTTZ-MCM-41) has been
      characterized by powder X-ray diffraction, nitrogen gas sorption, FT-IR and MAS
      NMR spectroscopy, thermogravimetry, and elemental analysis. The solid was
      employed as a Zn(II) adsorbent from aqueous solutions at room temperature. The
      effect of several variables (stirring time, pH, metal concentration, addition of
      ethanol, presence of other metals in the medium) has been studied using batch and
      column techniques. Flame atomic absorption spectrometry was used to determine the
      Zn(II) concentration in the filtrate or in the eluted solution after the
      adsorption process. Results obtained indicate that under the optimum conditions
      (pH 8 and 2 h stirring time), the maximum adsorption value for Zn(II) was 1.59+/
      0.01 mmol/g, whereas the adsorption capacity of the unmodified mesoporous silica
      was about 0.010+/-0.001 mmol/g. On the other hand, the Zn(II) adsorption on the
      MTTZ-MCM-41 was independent of the presence of ethanol and other metals (Cu(II),
      Mn(II), Ca(II), and Mg(II)) in the medium. Finally, experiments carried out in
      order to study the regeneration capacity of the MTTZ-MCM-41 revealed that the
      adsorption capacity of this material was maintained after 3 cycles of the
      adsorption/desorption process.

PMID- 17532332
TI  - The stability of ultra-thin perfluoropolyether mixture films on the amorphous
      nitrogenated carbon surface.
AB  - The thermodynamic stability of boundary lubricant films based upon mixtures of
      liquid perfluoropolyethers (PFPEs) is reported. Mixtures of A20H-2000 with Zdols
      2000, 2500, and 4000 and Zdol-TX 2200 on amorphous carbon nitride films are
      investigated. An optical surface analyzer is used to image the autophobic
      dewetting of the mixture PFPE films. The critical dewetting thickness coincides
      with the monolayer thickness of the adsorbed mixture PFPE films as determined by
      the changes in the surface energy as a function of lubricant film thickness. The
      critical dewetting thickness varies linearly with mixture concentration.

PMID- 17532333
TI  - The N-terminal His-tag affects the enantioselectivity of staphylococcal lipases:
      a monolayer study.
AB  - In order to check the influence of the polyhistidine tag at the N-terminus of
      recombinant lipases, a comparative study on the interfacial properties of native
      and recombinant Staphylococcus simulans (SSL and rSSL) or Staphylococcus xylosus
      lipase (SXL and rSXL) was investigated using the monomolecular film technique. No
      phospholipase activity was detected with rSSL or rSXL when using different
      phospholipids spread as monomolecular films maintained at various surface
      pressures, suggesting that the His-tag in the N-terminus of the recombinant
      proteins, do not affect the substrate recognition. The critical surface pressure
      measured with monomolecular films of egg-PC was slightly lowered with the two
      recombinant proteins compared to the native SSL or SXL one. A kinetic study on
      the surface pressure dependency, stereoselectivity and regioselectivity of native
      and recombinant SSL or SXL was performed using three dicaprin isomers spread as
      monomolecular films at the air-water interface. Our results show clearly that the
      presence of polyhistidine tag at the N-terminus of SSL or SXL changes their
      stereo- and regioselectivity.

PMID- 17532334
TI  - Micellar kinetic effects in gemini micellar solutions: influence of sphere-to-rod
      transitions on kinetics.
AB  - The reactions 4-nitrobenzenesulfonate+Br(-) and methyl naphthalene-2
      sulfonate+Br(-) were studied in various water-ethylene glycol, EG,
      [C(12)H(25)(CH(3))(2)N(CH(2))(s)N(CH(3))(2)C(12)H(25)]Br(2) micellar solutions
      (12-s-12,2Br(-) with s=3-5 methylene groups). Results showed that the observed
      rate constant of the two reactions varied when a sphere-to-rod transition occurs.
      This morphological transition is accompanied by changes in the interfacial region
      water content and in its polarity. The micellar ionization degree is also
      altered, making the counterion interfacial concentration change. Finally,
      variations on the molar surfactant volume, V(m), also follow the sphere-to-rod
      transitions. A simple pseudophase kinetic model is inadequate for quantitatively
      discussing the kinetic micellar effects observed, since the changes accompanying
      micellar growth affect the second-order rate constant in the micellar
      pseudophase, the equilibrium binding constant and the surfactant molar volume,
      neither of them remaining constant in the whole surfactant concentration range.
      However, this simple model can be helpful in the treatment of kinetic data for
      surfactant concentrations below the morphological transitions, providing some
      interesting, although approximate, information.

PMID- 17532335
TI  - Unusual bigeminal rhythms.

PMID- 17532336
TI  - Value of the 12-lead resting electrocardiogram for the diagnosis of previous
      myocardial infarction in paced patients.
AB  - AIM: This study was conducted to assess the clinical value of the 12-lead
      electrocardiogram (ECG) for the diagnosis of previous myocardial infarction (MI)
      in permanently paced patients. METHODS: A total of 107 unselected patients with
      permanent pacemakers were retrospectively studied and divided into 3 groups:
      group 1 (control group): 38 patients without a history of MI (mean age, 67 +/- 16
      years; 20 men; ejection fraction 63% +/- 8%); group 2: 44 patients (mean age, 72
      +/- 11 years; 41 men) with documented previous MI (21 anterior, 23 inferior;
      ejection fraction 38% +/- 13%; P < .0001 vs group 1); group 3: 25 patients (mean
      age, 71 +/- 14 years; 24 men) with biventricular pacing for severe heart failure
      (16 ischemic, 9 nonischemic; ejection fraction 28% +/- 8%; P = .001 vs group 2, P
      < .0001 vs group 1). A surface 12-lead ECG with full ventricular capture was used
      for analysis. Comparing group 1 and group 2, the sensitivity, specificity,
      positive predictive value, negative predictive value, and overall accuracy of 5
      criteria was calculated: (1) Cabrera's sign (notching in the ascending limb of
      the S wave in lead V(3), V(4), or V(5)); (2) Chapman's sign (notching of the R
      wave in lead I, aVL, or V(6)); (3) presence of a qR in lead I, aVL, or V(6); (4)
      notching of QRS in lead II, III, or aVF; (5) presence of a qR in lead II, III, or
      aVF. RESULTS: To detect prior MI, sensitivity was moderate for Cabrera's sign
      (63.6%) and poor for all other ECG criteria ranging from 9.1% to 40.9%.
      Specificity was relatively high for all ECG criteria ranging from 81.6% to 100%.
      Combining all 5 ECG signs increased sensitivity to 86.4%, with a specificity of
      65.8% and an overall accuracy of 76.8% for the diagnosis of previous MI. None of
      the 5 criteria was particularly useful to assess the site of prior MI. In
      patients with biventricular pacing, the accuracy of the 5 ECG criteria was poor
      and the presence of a qR wave in lead I, aVL, or V6 appears nonspecific and
      related to pacing site. CONCLUSION: The ECG diagnosis of previous MI in paced
      patients remains a difficult challenge but the presence of 1 or more of the
      aforementioned ECG criteria may be clinically useful to detect previous MI,
      suggesting that these ECG signs should be widely taught during medical training.
      However, in patients with biventricular pacing, these ECG signs are of no value.

PMID- 17532337
TI  - The effects of enhanced external counterpulsation on time- and frequency-domain
      measures of heart rate variability.
AB  - BACKGROUND AND PURPOSE: We hypothesized that symptom improvement from enhanced
      external counterpulsation (EECP) is related to improved heart rate variability
      (HRV). METHODS: This prospective, multicenter study enrolled 27 patients with
      angina who underwent 48-hour ambulatory electrocardiogram monitoring at baseline,
      immediately after 35 hours of EECP, and at 1 month. Primary end points included
      change in time-domain (SD of normal-to-normal intervals) and frequency-domain
      HRV. RESULTS: Twenty-four patients completed the full course of EECP therapy and
      3 ambulatory electrocardiograms. There were no significant changes in time-domain
      HRV measures after EECP. Patients younger than 65 years and those with heart
      failure had improved SD of normal-to-normal interval after EECP (P = .02).
      Although frequency-domain HRV measures did not change in the overall cohort,
      patients with diabetes had improved daytime low-frequency power (P = .016).
      CONCLUSIONS: There was no significant change in the time- or frequency-domain HRV
      measures after EECP. In diabetic individuals, there was an increase in low
      frequency HRV, which has been associated with reduced mortality.

PMID- 17532338
TI  - Tuning lambda6-85 towards downhill folding at its melting temperature.
AB  - The five-helix bundle lambda6-85* is a fast two-state folder. Several stabilized
      mutants have been reported to fold kinetically near-downhill or downhill. These
      mutants undergo a transition to two-state folding kinetics when heated. It has
      been suggested that this transition is caused by increased hydrophobicity at
      higher temperature. Here we investigate two histidine-containing mutants of
      lambda6-85* to see if a weaker hydrophobic core can extend the temperature range
      of downhill folding. The very stable lambdaHA is the fastest-folding lambda
      repressor to date (k(f)(-1) approximately k(obs)(-1)=2.3 micros at 44 degrees C).
      It folds downhill at low temperature, but transits back to two-state folding at
      its unfolding midpoint. lambdaHG has a weakened hydrophobic core. It is less
      stable than some slower folding mutants of lambda6-85*, and it has more exposed
      hydrophobic surface area in the folded state. This mutant nonetheless folds very
      rapidly, and has the non-exponential folding kinetics of an incipient downhill
      folder even at the unfolding midpoint (k(m)(-1) approximately 2 micros, k(a)(
      1)=15 micros at 56 degrees C). We also compare the thermodynamic melting
      transition of lambdaHG with the nominal two-state folding mutant lambdaQG, which
      has a similar melting temperature. Unlike lambdaQG, lambdaHG yields fluorescence
      wavelength-dependent cooperativities and probe-dependent melting temperatures.
      This result combined with previous work shows that the energy landscapes of
      lambda repressor mutants support all standard folding mechanisms.

PMID- 17532339
TI  - Crystal structure of pyruvate dehydrogenase phosphatase 1 and its functional
      implications.
AB  - Pyruvate dehydrogenase phosphatase 1 (PDP1) catalyzes dephosphorylation of
      pyruvate dehydrogenase (E1) in the mammalian pyruvate dehydrogenase complex
      (PDC), whose activity is regulated by the phosphorylation-dephosphorylation cycle
      by the corresponding protein kinases (PDHKs) and phosphatases. The activity of
      PDP1 is greatly enhanced through Ca2+ -dependent binding of the catalytic subunit
      (PDP1c) to the L2 (inner lipoyl) domain of dihydrolipoyl acetyltransferase (E2),
      which is also integrated in PDC. Here, we report the crystal structure of the rat
      PDP1c at 1.8 A resolution. The structure reveals that PDP1 belongs to the PPM
      family of protein serine/threonine phosphatases, which, in spite of a low level
      of sequence identity, share the structural core consisting of the central beta
      sandwich flanked on both sides by loops and alpha-helices. Consistent with the
      previous studies, two well-fixed magnesium ions are coordinated by five active
      site residues and five water molecules in the PDP1c catalytic center. Structural
      analysis indicates that, while the central portion of the PDP1c molecule is
      highly conserved among the members of the PPM protein family, a number of
      structural insertions and deletions located at the periphery of PDP1c likely
      define its functional specificity towards the PDC. One notable feature of PDP1c
      is a long insertion (residues 98-151) forming a unique hydrophobic pocket on the
      surface that likely accommodates the lipoyl moiety of the E2 domain in a fashion
      similar to that of PDHKs. The cavity, however, appears more open than in PDHK,
      suggesting that its closure may be required to achieve tight, specific binding of
      the lipoic acid. We propose a mechanism in which the closure of the lipoic acid
      binding site is triggered by the formation of the intermolecular (PDP1c/L2) Ca2+
      binding site in a manner reminiscent of the Ca2+ -induced closure of the
      regulatory domain of troponin C.

PMID- 17532340
TI  - Folding amphipathic helices into membranes: amphiphilicity trumps hydrophobicity.
AB  - High amphiphilicity is a hallmark of interfacial helices in membrane proteins and
      membrane-active peptides, such as toxins and antimicrobial peptides. Although
      there is general agreement that amphiphilicity is important for membrane
      interface binding, an unanswered question is its importance relative to simple
      hydrophobicity-driven partitioning. We have examined this fundamental question
      using measurements of the interfacial partitioning of a family of 17-residue
      amidated-acetylated peptides into both neutral and anionic lipid vesicles.
      Composed only of Ala, Leu, and Gln residues, the amino acid sequences of the
      peptides were varied to change peptide amphiphilicity without changing total
      hydrophobicity. We found that peptide helicity in water and interface increased
      linearly with hydrophobic moment, as did the favorable peptide partitioning free
      energy. This observation provides simple tools for designing amphipathic helical
      peptides. Finally, our results show that helical amphiphilicity is far more
      important for interfacial binding than simple hydrophobicity.

PMID- 17532341
TI  - Prion and non-prion amyloids of the HET-s prion forming domain.
AB  - HET-s is a prion protein of the fungus Podospora anserina. A plausible structural
      model for the infectious amyloid fold of the HET-s prion-forming domain, HET
      s(218-289), makes it an attractive system to study structure-function
      relationships in amyloid assembly and prion propagation. Here, we report on the
      diversity of HET-s(218-289) amyloids formed in vitro. We distinguish two types
      formed at pH 7 from fibrils formed at pH 2, on morphological grounds. Unlike pH 7
      fibrils, the pH 2 fibrils show very little if any prion infectivity. They also
      differ in ThT-binding, resistance to denaturants, assembly kinetics, secondary
      structure, and intrinsic fluorescence. Both contain 5 nm fibrils, either bundled
      or disordered (pH 7) or as tightly twisted protofibrils (pH 2). We show that
      electrostatic interactions are critical for the formation and stability of the
      infectious prion fold given in the current model. The altered properties of the
      amyloid assembled at pH 2 may arise from a perturbation in the subunit fold or
      fibrillar stacking.

PMID- 17532342
TI  - Hypothermia: comparing technology.
AB  - Hypothermia has recently been shown to be beneficial in certain clinical settings
      of acute brain injury, such as cardiac arrest. The available technology to induce
      and maintain this state is advancing quickly. This review will focus on the
      current state of available technology and devices as well as their limitations in
      attaining this potentially neuroprotective state. Furthermore, we will present
      the efficacy of the individual systems as well as potential side effects and
      complications that are associated with the technology chosen.

PMID- 17532343
TI  - Modeling within-host HIV-1 dynamics and the evolution of drug resistance: trade
      offs between viral enzyme function and drug susceptibility.
AB  - There are many biological steps between viral infection of CD4(+) T cells and the
      production of HIV-1 virions. Here we incorporate an eclipse phase, representing
      the stage in which infected T cells have not started to produce new virus, into a
      simple HIV-1 model. Model calculations suggest that the quicker infected T cells
      progress from the eclipse stage to the productively infected stage, the more
      likely that a viral strain will persist. Long-term treatment effectiveness of
      antiretroviral drugs is often hindered by the frequent emergence of drug
      resistant virus during therapy. We link drug resistance to both the rate of
      progression of the eclipse phase and the rate of viral production of the
      resistant strain, and explore how the resistant strain could evolve to maximize
      its within-host viral fitness. We obtained the optimal progression rate and the
      optimal viral production rate, which maximize the fitness of a drug resistant
      strain in the presence of drugs. We show that the window of opportunity for
      invasion of drug resistant strains is widened for a higher level of drug efficacy
      provided that the treatment is not potent enough to eradicate both the sensitive
      and resistant virus.

PMID- 17532344
TI  - Singular solutions of the diffusion equation of population genetics.
AB  - The forward diffusion equation for gene frequency dynamics is solved subject to
      the condition that the total probability is conserved at all times. This can lead
      to solutions developing singular spikes (Dirac delta functions) at the gene
      frequencies 0 and 1. When such spikes appear in solutions they signal gene loss
      or gene fixation, with the "weight" associated with the spikes corresponding to
      the probability of loss or fixation. The forward diffusion equation is thus
      solved for all gene frequencies, namely the absorbing frequencies of 0 and 1
      along with the continuous range of gene frequencies on the interval (0,1) that
      excludes the frequencies of 0 and 1. Previously, the probabilities of the
      absorbing frequencies of 0 and 1 were found by appeal to the backward diffusion
      equation, while those in the continuous range (0,1) were found from the forward
      diffusion equation. Our unified approach does not require two separate equations
      for a complete dynamical treatment of all gene frequencies within a diffusion
      approximation framework. For cases involving mutation, migration and selection,
      it is shown that a property of the deterministic part of gene frequency dynamics
      determines when fixation and loss can occur. It is also shown how solution of the
      forward equation, at long times, leads to the standard result for the fixation
      probability.

PMID- 17532345
TI  - Regulation of LPS stimulated ROS production in peritoneal macrophages from
      alloxan-induced diabetic rats: involvement of high glucose and PPARgamma.
AB  - An increased occurrence of long term bacterial infections is common in diabetic
      patients. Bacterial cell wall components are described as the main antigenic
      agents from these microorganisms and high blood glucose levels are suggested to
      be involved in altered immune response. Hyperglycemia is reported to alter
      macrophages response to lipopolysaccharide (LPS) and peroxisome proliferators
      activated receptor gamma (PPARgamma) expression. Additionally, glucose is the
      main metabolic fuel for reduced nicotinamide adenine dinucleotide phosphate
      (NADPH) production by pentose phosphate shunt. In this work, lipopolysaccharide
      (LPS) stimulated reactive oxygen species (ROS) and nitrite production were
      evaluated in peritoneal macrophages from alloxan-induced diabetic rats. Cytosolic
      dehydrogenases and PPARgamma expression were also investigated. LPS was
      ineffective to stimulate ROS and nitrite production in peritoneal macrophages
      from diabetic rats, which presented increased glucose-6-phosphate dehydrogenase
      and malate dehydrogenase activity. In RAW 264.7 macrophages, acute high glucose
      treatment abolished LPS stimulated ROS production, with no effect on nitrite and
      dehydrogenase activities. Peritoneal macrophages from alloxan-treated rats
      presented reduced PPARgamma expression. Treating RAW 264.7 macrophages with a
      PPARgamma antagonist resulted in defective ROS production in response to LPS,
      however, stimulated nitrite production was unaltered. In conclusion, in the
      present study we have reported reduced nitric oxide and reactive oxygen species
      production in LPS-treated peritoneal macrophages from alloxan-induced diabetic
      rats. The reduced production of reactive oxygen species seems to be dependent on
      elevated glucose levels and reduced PPARgamma expression.

PMID- 17532346
TI  - Obesity influences the food consumption and cytokine pattern in ghrelin-treated
      endotoxemic rats.
AB  - Obese patients have an increased incidence of systemic infections and higher
      morbidity and mortality rates than normal weight subjects. Ghrelin is a potent
      orexigenic signal from the stomach and seems to play a role in the generation and
      control of immune interactions. To examine a possible benefit of a single ghrelin
      application on acute endotoxemia, chronic intravenous (i.v.) cannulated lean and
      diet-induced obese male LEW rats were treated with a bolus injection of either
      ghrelin (10 nmol/kg) or vehicle, 10 min prior to a challenge with a sublethal
      bolus of endotoxin (100 microg/kg) or vehicle. Multiple blood samples were taken
      within a period from 24 h before the experiment up to 24 h after the endotoxin
      challenge to measure ghrelin and cytokine levels. Additionally, food consumption
      was recorded and ghrelin expression in fore- and glandular stomach was evaluated
      immunohistochemically. Despite higher serum ghrelin levels, the food consumption
      was significantly decreased in obese endotoxemic rats compared to lean
      littermates after ghrelin treatment. Furthermore we could show an increase of
      anti-inflammatory IL-10 serum levels after ghrelin treatment of normal weight
      endotoxemic and an opposite effect in obese animals. As the therapy of disease
      associated cachexia and various immunological problems in endotoxemia is still
      insufficient, peptides such as ghrelin with their modulating abilities for the
      endocrine and the immune system are of special interest. However, the present
      study shows that the beneficial effects of ghrelin were attenuated in obese
      endotoxemic animals. These data further document the necessity to differentiate
      between normal weight and obese subjects in the attempt to establish ghrelin as a
      therapeutic target in endotoxemia.

PMID- 17532347
TI  - Combination of dipeptidylpeptidase IV inhibitor and low dose thiazolidinedione:
      preclinical efficacy and safety in db/db mice.
AB  - Thiazolidinediones (TZDs) are currently the most efficacious class of oral
      antidiabetics. However, they carry the burden of weight gain and haemodilution,
      which may lead to cardiovascular complications. The present study was designed to
      ascertain whether a combination of dipeptidyl peptidase IV (DPP IV) inhibitor
      with low dose of a thiazolidinedione absolves TZD associated weight gain and
      oedema without compromising its efficacy. In this study, we examined the efficacy
      and safety of lower dose (1 mg/kg/day) of rosiglitazone, a thiazolidinedione, in
      combination with 5 mg/kg/day dose of LAF-237 (vildagliptin), a known DPP IV
      inhibitor, in aged db/db mice after 14 days of treatment and compared the
      combination with therapeutic dose (10 mg/kg) of rosiglitazone. The combination
      therapy showed similar efficacy as that of 10 mg/kg/day rosiglitazone in lowering
      random blood glucose (53.8%, p<0.001 and 54.3%, p<0.001 respectively), AUC ((0
      120) min) during oral glucose tolerance test (OGTT) (38.6 %, p<0.01; 38.3%,
      p<0.01 respectively) and triglyceride levels (63.9% and 61% respectively;
      p<0.01). Plasma active glucagon like peptide-1 (GLP-1) and insulin levels were
      found to be elevated significantly (p<0.01 and p<0.05 respectively) in both LAF
      237 and combination treated groups following oral glucose load. LAF-237 alone had
      no effect on random glucose and glucose excursion during OGTT in severely
      diabetic db/db mice. Interestingly, the combination treatment showed no
      significant increase in body weight as compared to the robust weight gain by
      therapeutic dose of rosiglitazone. Rosiglitazone at 10 mg/kg/day showed
      significant reduction (p<0.05) in haematocrit, RBC count, haemoglobin pointing
      towards haemodilution associated with increased mRNA expression of Na(+), K(+)
      ATPase-alpha and epithelial sodium channel gamma (ENaCgamma) in kidney. The
      combination therapy escaped these adverse effects. The results suggest that
      combination of DPP IV inhibitor with low dose of thiazolidinedione can interact
      synergistically to represent a therapeutic advantage for the clinical treatment
      of type 2 diabetes without the adverse effects of haemodilution and weight gain
      associated with thiazolidinediones.

PMID- 17532348
TI  - Effects of atorvastatin therapy on hypercholesterolemic rabbits with respect to
      oxidative stress, nitric oxide pathway and homocysteine.
AB  - Hypercholesterolemia is characterized with changes in lipid profile, nitric oxide
      pathway and oxidative stress markers. This study is designed to evaluate the
      effects of hypercholesterolemic diet and atorvastatin therapy on oxidative
      stress, lipid peroxide and thiobarbituric acid reactive substances (TBARS), NO
      pathway markers, nitric oxide(NO) and asymmetric dimethylarginine (ADMA),
      homocysteine, and paraoxonase activity (PON1) in rabbits. Twenty rabbits fed with
      high-cholesterol diet for 8 weeks were randomly divided into 2 groups on the
      fourth week of the hypercholesterolemic diet. First group was fed with high
      cholesterol diet alone, whereas the second group with the same cholesterol diet
      plus atorvastatin (0.3 mg/kg/day) for 4 weeks. High-cholesterol diet increased
      total cholesterol, low density lipoprotein (LDL-C), high density lipoprotein (HDL
      C), ADMA, TBARS and lipid peroxide levels and reduced PON1 activity and NO levels
      in rabbits. Four weeks of atorvastatin therapy significantly increased HDL-C,
      PON1 activity and reduced LDL-C, TBARS and lipid peroxide concentrations.
      Atorvastatin therapy is beneficial in decreasing oxidative stress related with
      hypercholesterolemia, mainly affecting lipid profile and PON1 activity.

PMID- 17532349
TI  - Persistent organic pollutants carried by synthetic polymers in the ocean
      environment.
AB  - Thermoplastic resin pellets are melted and formed into an enormous number of
      inexpensive consumer goods, many of which are discarded after a relatively short
      period of use, dropped haphazardly onto watersheds and then make their way to the
      ocean where some get ingested by marine life. In 2003 and 2004 pre-production
      thermoplastic resin pellets and post-consumer plastic fragments were collected
      and analyzed for contamination for persistent organic pollutants (POPs). Samples
      were taken from the North Pacific Gyre, and selected sites in California, Hawaii,
      and from Guadalupe Island, Mexico. The total concentration of PCBs ranged from 27
      to 980 ng/g; DDTs from 22 to 7100 ng/g and PAHs from 39 to 1200 ng/g, and
      aliphatic hydrocarbons from 1.1 to 8600 microg/g. Analytical methods were
      developed to extract, concentrate and identify POPs that may have accumulated on
      plastic fragments and plastic pellets. The results of this study confirm that
      plastic debris is a trap for POPs.

PMID- 17532350
TI  - Comments on Carpenter, A., 2007 "The Bonn Agreement Aerial Surveillance
      Programme: Trends in North Sea Oil Pollution 1986-2004", Marine Pollution
      Bulletin, vol. 54, 2007, pp. 149-163.

PMID- 17532351
TI  - Chemotypes in Achillea collina based on sesquiterpene lactone profile.
AB  - The lactone profile of six origins of Achillea collina growing in Bulgaria was
      studied and significant variability was observed. The reasons for the differences
      in the lactone composition are discussed. Twenty-five components in total were
      isolated and identified, while the presence of ten lactones was proved by
      intensive TLC analysis in comparison with reference compounds. The structures of
      the components 17, 20, 25-30 were established by spectroscopic methods. The
      structure of 7, a cyclization product of 6, was also discussed. The anti
      inflammatory activity of some extracts, fractions and individual compounds was
      tested in vitro by determining the inhibitory effects on induced human
      neutrophils.

PMID- 17532352
TI  - Iridoids from Scutellaria albida ssp. albida.
AB  - Three iridoid glycosides, 6'-O-E-p-coumaroylgardoside (1), 6'-O-p-E-coumaroyl-8
      epi-loganic acid (2) and scutelloside (3) were isolated from the aerial parts of
      Scutellaria albida subsp. albida, in addition to an anomeric mixture in
      equilibrium of one iridoid aglycone (4, 4a), nine iridoid glycosides (5-13), four
      known phenylethanoid glycosides (14-17), and six known phenolic derivatives (18
      23).

PMID- 17532353
TI  - [A simple tissue expansion device for scalp defect].
AB  - INTRODUCTION: The closure of scalp defects requires various procedures, but
      unfortunately with a high rate of sequels. OBSERVATION: The authors report their
      experience regarding a large pilomatrixoma of the scalp. The closure of an 8 by
      10 cm defect resulting from excision was achieved using a simple tissular
      extension device during 20 days. The scar aspect was very satisfactory. The
      device is derived from Cohn's model. It is made of simple and widely used
      material (vascular lacks, staples). DISCUSSION: This simplicity and efficiency of
      tissular extension devices has been proved. Nevertheless, their use may be
      restricted. This limitation often results from a high cost and difficulty in
      applying the adequate tension to the wound edges. Excessive tension may lead to
      cutaneous necrosis. The use of a simple device derived from Cohn's model seems
      interesting considering its efficiency, reliability, and low cost.

PMID- 17532354
TI  - [Classification of vascular tumors and malformations: basis for classification
      and clinical purpose].
AB  - Vascular anomalies are a complex pathological group. They are especially
      difficult to study because of confusion in the terminology used. The
      classification developed by the ISSVA (International Society for the Study of
      Vascular Anomalies) now allows using a common scientific language. The
      classification is based on clinical, radiological, hemodynamic, and histological
      arguments. There are two groups of lesions: vascular tumors and vascular
      malformations. Vascular tumors are associated to vascular proliferation. They are
      called hemangioma and can be infantile or congenital. Vascular malformations are
      associated to vessels with morphologic anomalies. They are classified according
      to the distorted vessel type, capillary, venous, lymphatic, and arteriovenous).
      Such a classification has many implications. It is a guide for the orientation of
      radiological exams and treatment of vascular anomalies. The management of these
      anomalies is still difficult and must involve an interdisciplinary approach.

PMID- 17532355
TI  - [Synovial cyst of the temporomandibular joint].
AB  - OBSERVATION: A 30-year-old patient presented with a left painful pre-auricular
      tumefaction for one year. CT-scan suggested the diagnosis of temporomandibular
      synovial cyst or first branchial cleft cyst. This was confirmed by surgery.
      DISCUSSION: Temporomandibular synovial cysts are rare, the etiology is not
      documented. Revealing symptoms are those mentioned above. The common treatment is
      surgery.

PMID- 17532356
TI  - [Is condylar resorption a contra-indication for surgery?].
AB  - INTRODUCTION: Idiopathic condylar resorption, often fortuitously discovered when
      performing orthodontic-surgical assessment, is a clinical entity in itself. There
      is a significant risk of postoperative degenerating and worsening. Is this
      sufficient to contra-indicate orthognathic surgery? The authors suggest an answer
      after studying a series of patients. MATERIAL AND METHOD: A retrospective study
      of 10 consecutive patients was made from July 1999 to October 2004. The
      preoperative assessment was triple: clinical, radiological and photographic. At
      least 6 months of occlusal, radiological and morphological stability was observed
      before any therapy was initiated. A fixed orthodontic set-up was placed and
      patients were regularly followed by a speech therapist for parafunctions.
      Stability of the occlusal correction, acquisition of a more harmonious aesthetic
      profile, and resolution of joint symptomatology were used to define therapeutic
      success at one year. RESULTS: All patients were female. Resorption affected the
      mandibular side of the joint in all cases and the temporal side in 7 cases. Three
      types of osteotomies were performed: maxillary (N=1), mandibular (N=5), and
      bibasilar (N=4). Genioplasty was not systematic. Joint symptoms were resolved in
      all cases. Postoperative occlusion corresponded to the therapeutic project in 9
      cases. All patients were aesthetically improved. DISCUSSION: Idiopathic condylar
      resorption is not a contra-indication for orthognathic surgery. However, this
      treatment requires meeting and respecting four principles: a minimal delay of 6
      months of occlusal, radiological, and morphological stability, an adapted and
      meticulous surgical technique, early and prolonged parafunction therapy, and a
      close follow-up of the patients.

PMID- 17532357
TI  - Proteins, lethality and in vivo effects of Iurus dufoureius asiaticus scorpion
      venom.
AB  - Iurus dufoureius asiaticus, Birula, 1903 scorpions were collected in Mugla
      province located in the Aegean region, Turkey. There are few number of
      publications about I.d. asiaticus, and there are no data regarding minimal lethal
      dose and effects of the scorpion venom till now. This is the first study about
      toxicity and effects of I.d. asiaticus scorpion venom in mice. Previously, most
      of the proteins in venom of I.d. asiaticus from Aydin region in Turkey were
      reported to be between 14 and 205 kDa in size. In this study, we determined the
      electrophoretic protein pattern of the venom taken from Mugla province to be
      between 29 and 116 kDa by SDS-PAGE. Intracerebroventricular (i.c.v.) was
      determined instead of s.c. injection since there were no deaths in any s.c. test
      groups. The LD(50) of I.d. asiaticus scorpion venom was found to be 47.7
      microg/20 g mouse by i.c.v. injection route. After s.c. injection venom, mice
      were shown any intoxication symptoms. On the other hand, after i.c.v.
      administration of venom, mice showed symptoms such as excitability, hyper
      salivation, weakness, paralysis, coma and resulting in death. The possible cause
      of death could be due to multi-system organ failure depending on the toxic effect
      of the venom. These both results showed that the venom was not lethal on s.c.
      injection, but it was lethal on i.c.v. injection. This may imply that the
      scorpion is of little danger to humans.

PMID- 17532358
TI  - Platelet activating factor receptors drive CXC chemokine production, neutrophil
      influx and edema formation in the lungs of mice injected with Tityus serrulatus
      venom.
AB  - Lung injury is a common finding and a frequent cause of death in cases of severe
      human envenoming by scorpion sting. The present work investigated the effects of
      pretreatment with a platelet activation factor receptor (PAFR) antagonist and a
      CXCR2 inhibitor on the lung injury induced by subcutaneous injection of Tityus
      serrulatus venom (TsV) in mice. Lung injury was assessed by evaluating the
      extravasation of Evans blue dye, as an index of increased vascular permeability,
      the neutrophil accumulation (mieloperoxidase activity), the concentration of
      tumor necrosis factor-alpha (TNF-alpha) and the chemokine KC in the lung after
      TsV administration. Neutrophil influx was preceded by the production of KC and
      dependent on CXCR2, as shown by the ability of repertaxin, a CXCR2 inhibitor, to
      prevent an increase of MPO activity in the lung. Repertaxin had no effect on TsV
      induced lethality. The PAFR antagonist (UK-74,505) significantly reduced TsV
      induced vascular permeability changes and neutrophil influx in the lungs. The
      inhibition of neutrophil influx was associated with inhibition of the production
      of the CXCR2-active chemokine KC. UK-74,505 had no effect on the lethality
      induced by TsV. In conclusion, these results show that the influx of neutrophils
      in the lungs of mice injected with TsV is dependent on the activation of PAFR and
      on PAFR-dependent production of the chemokine KC as well as activation of CXCR2
      on neutrophils. Although lung injury may contribute to late lethality after TsV
      envenoming, acute lethality is not modified by inhibitors of neutrophil influx.

PMID- 17532359
TI  - Substitution of alanine for tyrosine-64 in the fingers subdomain of M-MuLV
      reverse transcriptase impairs strand displacement synthesis and blocks viral
      replication in vivo.
AB  - A distinctive property of reverse transcriptase is the ability to carry out
      strand displacement synthesis in the absence of accessory proteins such as
      helicases or single-strand DNA binding proteins. Structure-function studies
      indicate that the fingers subdomain in HIV-1 reverse transcriptase contacts the
      template strand downstream of the primer terminus and is involved in strand
      displacement synthesis. Based on structural comparisons to the HIV-1 enzyme, we
      made single amino acid substitutions at the Tyr-64 and Leu-99 positions in the
      fingers subdomain of the M-MuLV reverse transcriptase to ask whether this
      subdomain has a similar role in displacement synthesis. In vitro assays comparing
      non-displacement versus displacement synthesis revealed that substitution of
      alanine at Tyr-64 generated a reverse transcriptase that was impaired in its
      capacity to carry out DNA and RNA displacement synthesis without affecting
      polymerase processivity or RNase H activity. However, substitution of Tyr-64 with
      phenylalanine and a variety of substitutions at position Leu-99 had no specific
      effect on displacement synthesis. The Y64A substitution prevented viral
      replication in vivo, and Y64A virus generated reduced levels of reverse
      transcription intermediates at all steps beyond the synthesis of minus strong
      stop DNA. The role of the fingers subdomain and in particular the possible
      contributions of the Tyr-64 residue in displacement synthesis are discussed.

PMID- 17532360
TI  - Temporal and spatial frequencies interact in the contrast transfer function of
      the pattern electroretinogram.
AB  - The contrast transfer function (CTF) of the pattern electroretinogram (PERG)
      depends on temporal frequency. For transient stimulation it is fully linear; at
      faster stimulation rates it becomes strongly non-linear with an accelerated
      shape. In this study we investigated a range of stimulus parameters with the aim
      of studying the influence of temporal and spatial frequencies, as well as
      contrast levels, on the CTF; effects were quantified via an "index of linearity"
      IL. Both reversal rate and check size influenced linearity (p<.001), examples: At
      a constant check size of 0.8 degrees, 7.7 rps: IL=1.0; 0.8 degrees/24 rps:
      IL=0.5; at a constant reversal rate of 19 rps, IL was 0.5 for 0.8 degrees, but
      rose to 0.8 both for 0.2 degrees and 18 degrees. The reason for this complex
      response surface remains a puzzle, it cannot be explained by varying
      parvo/magnocellular contributions, and its possible influences on recordings in
      patients merit further studies.

PMID- 17532361
TI  - Eye movements during rapid pointing under risk.
AB  - We recorded saccadic eye movements during visually-guided rapid pointing
      movements under risk. We intended to determine whether saccadic end points are
      necessarily tied to the goals of rapid pointing movements or whether, when the
      visual features of a display and the goals of a pointing movement are different,
      saccades are driven by low-level features of the visual stimulus. Subjects
      pointed at a stimulus configuration consisting of a target region and a penalty
      region. Each target hit yielded a gain of points; each penalty hit incurred a
      loss of points. Late responses were penalized. The luminance of either target or
      penalty region was indicated by a disk which differed significantly from the
      background in luminance, while the other region was indicated by a thin circle.
      In subsequent experiments, we varied the visual salience of the stimulus
      configuration and found that manual responses followed near-optimal strategies
      maximizing expected gain, independent of the salience of the target region. We
      suggest that the final eye position is partially pre-programmed prior to hand
      movement initiation. While we found that manipulations of the visual salience of
      the display determined the end point of the initial saccade we also found that
      subsequent saccades are driven by the goal of the hand movement.

PMID- 17532362
TI  - Effects of nutrients on biofilm formation and detachment of a Pseudomonas putida
      strain isolated from a paper machine.
AB  - The aim of this study was to determine the effect of varying nutrient conditions
      on biofilm formation of a Pseudomonas putida strain isolated from a paper machine
      under controlled conditions. Biofilm accumulation, was investigated using a
      laminar flow cell reactor in a defined mineral medium. Our results indicate that
      increasing nutrient concentration (from 0.1 to 0.5 gl(-1) glucose, C/N=40,
      C/P=100) or phosphate concentration (from C/P=200 to C/P=100) increased the rate
      and extent of biofilm accumulation, however, higher nutrient (1 gl(-1) glucose,
      C/N=40, C/P=100) or phosphate (C/P=50) concentration reduced biofilm accumulation
      rate because of a higher detachment. The rate and extent of biofilm accumulation
      increased with nitrogen concentration (from C/N=90 to C/N=20). Detachment is a
      key parameter that influences biofilm accumulation since the early stage (2h) of
      colonisation and strongly depends on nutrient conditions. In practice,
      controlling nutrient levels may be interesting to reduce biofilm formation in the
      paper industry.

PMID- 17532363
TI  - Cadmium-induced oxidative stress and response of the ascorbate-glutathione cycle
      in Bechmeria nivea (L.) Gaud.
AB  - Bechmeria nivea (L.) Gaud. (ramie) seedlings subjected to a series of cadmium
      (Cd) concentrations (0, 1, 3 and 7 mg l(-1)) over a 10d period were investigated
      with regard to the uptake and distribution of Cd, its effect on membrane lipid
      and chlorophyll synthesis, and response of the ascorbate-glutathione cycle in
      both leaves and roots. Increased Cd level in the medium resulted in a significant
      enhancement of Cd concentration in tested plants, with most accumulation in
      roots. Ramie under Cd stress exhibited increased level of lipid peroxidation, as
      was evidenced by the increased malondialdehyde content (MDA, an index of lipid
      peroxidation) in leaves and roots. Shorter exposure to lower Cd concentrations (1
      and 3 mg l(-1)) led to a stimulation of chlorophyll synthesis, while longer
      exposure and higher Cd concentration (7 mg l(-1)) led to a remarkable breakdown
      of chlorophyll, suggesting that Cd caused oxidative stress in ramie. The
      antioxidant system as represented by the ascorbate-glutathione pathway was
      clearly activated following Cd exposure. An overall increase in the metabolite
      levels and major constituting enzyme activities (ascorbate peroxidase APX and
      glutathione reductase GR) was observed in ramie treated with 1 and 3 mg l(-1) Cd
      throughout the entire experimental period, while prolongation of exposure to 7 mg
      l(-1) Cd resulted in decrease of GR activity and GSH pool in roots which may
      limit the operation of the whole cycle. Results suggest that Cd-induced oxidative
      damage in ramie is closely associated with the efficiency of its intrinsic
      antioxidant mechanisms and the accelerated operation of ascorbate-glutathione
      cycle provides ramie with enhanced Cd-stress tolerance.

PMID- 17532364
TI  - Spectroscopic and conformational properties of size-fractions separated from a
      lignite humic acid.
AB  - A lignite humic acid (HA) was fractionated by preparative high performance size
      exclusion chromatography (HPSEC) in seven different size-fractions. The size
      fractions were characterized by cross polarization (CP) magic angle spinning
      (MAS) (13)C NMR spectroscopy and a further analytical HPSEC elution under UV and
      fluorescence detection. The alkyl hydrophobic components mainly distributed in
      the largest molecular-size-fraction, whereas the amount of oxidized carbons
      increased with decreasing size of fractions. Cross polarization time (T(CH)) and
      proton spin-lattice relaxation time in the rotating frame (T(1rho)(H)) were
      measured from variable contact time (VCT) experiments. The bulk HA was
      characterized by the shortest T(CH) values and the longest T(1rho)(H) values
      which suggested, respectively, one. an aggregation of components in a large
      conformation that favored a fast H-C cross polarization, and, two. consequent
      steric hindrances that prevented fast local molecular motions and decreased
      proton relaxation rates. Conversely, the separated size-fractions showed longer
      T(CH) values and shorter T(1rho)(H) values than the bulk HA, thereby indicating
      that they were constituted by a larger number of mobile molecular conformations.
      The UV and fluorescence absorptions were both low in the large size-fractions
      that mainly contained alkyl carbons, whereas they increased in the olephinic- and
      aromatic-rich fractions with intermediate molecular-size, and decreased again in
      the smaller fractions which were predominantly composed by oxidized carbons.
      These results support the supramolecular structure of humic substances and
      indicate that the observed variation in conformational distribution in humic
      association may be used to explain environmental processes with additional
      precision.

PMID- 17532365
TI  - In vitro assessment of arsenic bioaccessibility in contaminated (anthropogenic
      and geogenic) soils.
AB  - Arsenic (As) bioaccessibility in contaminated soils (n=50) was assessed using the
      simplified bioaccessibility extraction test (SBET). Soils used in the study were
      collected from sites where As was used as an herbicide (railway corridor) or
      pesticide (cattle dip sites), from former gold mines and from highly mineralised
      locations containing geogenic As sources (gossans). In all but three soils, As
      bioaccessibility was less than 50% indicating that a significant proportion of
      the total As concentration may not be available for absorption in the
      gastrointestinal tract following incidental soil ingestion. When regression
      models were developed based on soil properties, the descriptive variables best
      able to describe As bioaccessibility in railway corridor, dip site and mine site
      soils were total As and total or dithionite-citrate extractable (free) iron (Fe).
      While As bioaccessibility could be predicted (r(2)=0.955, n=50) in these
      contaminated soils, As bioaccessibility for gossan soils was a poor fit using
      linear or multivariate regression analysis.

PMID- 17532366
TI  - 137Cs in the western South Pacific Ocean.
AB  - The 137Cs activities were determined for seawater samples from the East Caroline,
      Coral Sea, New Hebrides, South Fiji and Tasman Sea (two stations) Basins of the
      western South Pacific Ocean by gamma spectrometry using a low background Ge
      detector. The 137Cs activities ranged from 1.4 to 2.3 Bq m(-3) over the depth
      interval 0-250 m and decreased exponentially from the subsurface to 1000 m depth.
      The distribution profiles of 137Cs activity at these six western South Pacific
      Ocean stations did not differ from each other significantly. There was a
      remarkable difference for the vertical profiles of 137Cs activity between the
      East Caroline Basin station in this study and the GEOSECS (Geochemical Ocean
      Sections Study) station at the same latitude in the Equatorial Pacific Ocean; the
      137Cs inventory over the depth interval 100-1000 m increased from 400+/-30 Bq m(
      2) to 560+/-30 Bq m(-2) during the period from 1973 to 1992. The total 137Cs
      inventories in the western South Pacific Ocean ranged from 850+/-70 Bq m(-2) in
      the Coral Sea Basin to 1270+/-90 Bq m(-2) in the South Fiji Basin. Higher 137Cs
      inventories were observed at middle latitude stations in the subtropical gyre
      than at low latitude stations. The 137Cs inventories were 1.9-4.5 times (2.9+/
      0.7 on average) and 1.7-4.3 times (3.1+/-0.7 on average) higher than that of the
      expected deposition density of atmospheric global fallout at the same latitude
      and that of the estimated 137Cs deposition density in 10 degrees latitude by 10
      degrees longitude grid data obtained by Aoyama et al. [Aoyama M, Hirose K,
      Igarashi Y. Re-construction and updating our understanding on the global weapons
      tests 137Cs fallout. J Environ Monit 2006;8:431-438], respectively. The possible
      processes for higher 137Cs inventories in the western South Pacific Ocean than
      that of the expected deposition density of atmospheric global fallout may be
      attributable to the inter-hemisphere dispersion of the atmospheric nuclear
      weapons testing 137Cs from the northern stratosphere to the southern one and its
      subsequent deposition, and water-bearing transport of 137Cs from the North
      Pacific Ocean to the western South Pacific.

PMID- 17532367
TI  - Thrombin formation in vitro in response to shear-induced activation of platelets.
AB  - INTRODUCTION: Thromboembolic events caused by implanted vascular devices present
      serious medical challenges. In particular bileaflet mechanical heart valves
      (MHVs) are prone to thrombus formation in the hinge region due to a combination
      of high shear stress and stagnation regions. Most studies of shear-induced
      platelet activation and aggregation have been performed using viscometers,
      parallel plate flow, and other non-physiologic in vitro configurations. The
      present study investigated these events in a physiogically relevant environment
      in which thrombin formation in response to shear stress activation of platelets
      plays a more predominant role. MATERIALS AND METHODS: Anticoagulated (citrated)
      human blood was placed in a steady flow loop containing a 400 microm round
      orifice or various MHVs in the leakage position. Simultaneous blood
      recalcification enhanced the thrombus forming potential of the blood. Aggrastat
      and AN51 were used to block binding to the platelet GPIIb/IIIa and GPIb
      receptors, respectively, and aspirin was used to block thromboxane production.
      Thrombin generation was measured indirectly by the thrombin-antithrombin III
      assay. RESULTS AND CONCLUSIONS: Aggrastat, AN51, and aspirin all suppressed
      thrombin formation. Furthermore, histological results suggested important roles
      for vWF and fibrinogen in a two-step model of thrombus formation. Thus, thrombin
      is reproducibly formed in this in vitro system, a process that can be suppressed
      by blocking platelet activation. This system has the potential to investigate
      mechanisms and interventions for medical devices that contact with blood under
      varying shear stress conditions.

PMID- 17532368
TI  - Cystic fibrosis heterozygotes do not have increased platelet activation.
AB  - INTRODUCTION: We have previously demonstrated platelet hyperreactivity in cystic
      fibrosis (CF) patients. Carriers of one CF mutation (heterozygotes) have been
      shown to have abnormalities related to the presence of only one-half the normal
      amount of CF transmembrane conductance regulator protein. Platelet
      hyperreactivity in CF heterozygotes would be an important cardiovascular risk
      factor, since approximately 1 in 25 Caucasians is a CF carrier. MATERIALS AND
      METHODS: We used highly sensitive assays of platelet activation to assess the
      difference between 16 CF heterozygotes and 16 age- and sex-matched healthy
      controls without CF mutations. RESULTS: We found no difference in platelet
      activation between CF heterozygotes and controls. CONCLUSIONS: The 50% reduction
      in the CF transmembrane conductance regulator protein in heterozygotes is
      insufficient to cause platelet activation.

PMID- 17532369
TI  - Secondary cytoreductive surgery for isolated nodal recurrence in patients with
      epithelial ovarian cancer.

PMID- 17532370
TI  - History of childhood candy cigarette use is associated with tobacco smoking by
      adults.
AB  - OBJECTIVE: We examined whether childhood candy cigarette use was associated with
      adult tobacco smoking. METHODS: 25,887 U.S. adults from the Harris Poll Online
      (HPOL) were surveyed about current smoking status from November 2005 to May 2006.
      Respondents were randomly assigned to a yes/no item or a dose-response scale to
      assess candy cigarette use. Data were weighted to reflect the U.S. adult
      population. RESULTS: 26.4% of respondents reported current smoking and 29.4%
      reported former smoking. Candy cigarette use was reported by 88% of both current
      and former smokers and 78% of never smokers (p<or=0.001). Logistic regression
      showed that the odds of smoking for those who used candy cigarettes was 1.98 (95%
      CI: 1.77, 2.21) for ever (current plus former) smokers and 1.83 (1.59, 2.10) for
      current smokers, compared to those who had not used candy cigarettes. Odds for
      current and ever smoking increased with increasing candy cigarette use.
      CONCLUSION: History of candy cigarette use was associated with increased risk of
      ever and current smoking among this nationally representative online sample of
      adults. Odds of smoking increased as candy cigarette use increased; these
      relationships persisted when controlled for sociodemographics. Elimination of
      candy cigarettes may protect children from products that promote the social
      acceptability of smoking.

PMID- 17532371
TI  - The reliability of the Adolescent Sedentary Activity Questionnaire (ASAQ).
AB  - OBJECTIVE: To determine the test-retest reliability of a self-report
      questionnaire (the Adolescent Sedentary Activities Questionnaire; ASAQ) which
      assesses the time spent in a comprehensive range of sedentary activities, among
      school-aged young people. METHOD: Two-hundred and fifty school students aged 11
      15 years from four primary and four high schools in metropolitan Sydney (New
      South Wales, Australia) completed the questionnaire under the same conditions on
      two occasions, 2 weeks apart during Autumn, 2002. RESULTS: Test-retest
      correlations for time total spent in sedentary behavior were >or=0.70, except for
      Grade 6 boys (Intraclass correlation coefficient (ICC)=0.57, 95%CI: 0.25, 0.76).
      Repeatability was generally higher on week days compared with week end days. ICC
      values for travel and social activities tended to be lower than for the other
      categories of sedentary behavior. There was little difference in the reliability
      across age groups. CONCLUSIONS: ASAQ has good to excellent reliability in the
      measurement of a broad range of sedentary behaviors among young people. ASAQ has
      good face validity, but further validity testing is required to provide a
      complete assessment of the instrument.

PMID- 17532372
TI  - Functional paraganglioma of the middle mediastinum.
AB  - We describe a 49-year-old woman with refractory hypertension resulting from a
      functional paraganglioma of the middle mediastinum. After aggressive medical
      antihypertensive control and reduction of catecholamine production, she underwent
      surgical resection requiring transection and subsequent reconstruction of the
      aorta on cardiopulmonary bypass and circulatory arrest. We believe that this is
      the first report of a functionally active paraganglioma of the mediastinum
      requiring resection with cardiopulmonary bypass and aortic reconstruction.

PMID- 17532373
TI  - Whom does the Grail serve? A vision of transformation in thoracic surgery.

PMID- 17532374
TI  - Power and sample size: how many patients do I need?

PMID- 17532375
TI  - Who gains most? A 10-year experience with 611 thoracoscopic talc pleurodeses.
AB  - BACKGROUND: Thoracoscopic talc pleurodesis is a therapeutic option for recurrent
      pleural effusion. METHODS: This retrospective study included 611 patients who
      underwent thoracoscopic talc pleurodesis between 1994 and 2003. We analyzed the
      risk factors, efficiency, outcome, follow-up, and survival, while taking into
      consideration primary disease and general condition. RESULTS: The mean follow-up
      was 319 days (range, 31 to 1994). A total of 105 (17.2%) of 611 patients died
      within 30 days after treatment. Risk factors for death within 30 days included a
      Karnofsky index of less than 50%, a body mass index of less than 25 kg/m2,
      malignant disease, and male gender. Treatment was successful in 347 (68.6%) of
      506 patients, and 451 (89.1%) reported an improvement in symptoms. Previous
      thoracic irradiation and a chest tube drainage time exceeding 10 days negatively
      influenced the outcome of pleurodesis. The survival rate was negatively
      influenced by a preoperative Karnofsky index of less than 60% and by malignant
      disease. CONCLUSIONS: Patients with pleural effusion due to malignant disease
      gain from early pleurodesis. The most favorable outcome after talc pleurodesis
      was seen in women whose lungs were fully expandable, in patients whose Karnofsky
      index exceeded 60%, in patients whose body mass index was greater than 25 kg/m2,
      and in patients with benign disease.

PMID- 17532376
TI  - Localized organizing pneumonia: report of 21 cases.
AB  - BACKGROUND: Thoracic surgeons have limited experience with treating localized
      organizing pneumonia owing to its rare occurrence in routine clinical practice.
      METHODS: We retrospectively investigated the clinicopathologic features of 21
      patients with localized organizing pneumonia observed between 2001 and 2004.
      RESULTS: There were 15 men and 6 women. Mean age was 63 years. Eight patients
      (38%) were symptomatic. Computed tomographic scan showed a single lesion in 17
      patients (12 nodules and 5 masses) and bilateral lesions in 4. Wedge resection
      was performed in 16 patients and lobectomy in 5. There was no operative
      mortality. Follow-up was complete in all patients (range, 2 to 46 months; median,
      20 months). Surgery was curative in 15 of 17 patients with a single lesion, and
      no recurrence was observed (p < 0.005). The remaining 2 patients with a single
      lesion (2 masses) had a local relapse with the appearance of nodular lesions in
      the residual parenchyma. Both these patients received steroids with resolution of
      the lesions. All 4 patients with bilateral lesions who underwent surgery for
      diagnostic purposes received steroids with improvement of the radiologic aspect
      in 3 and stabilization of the lesions in 1. CONCLUSIONS: Clinical and radiologic
      findings of localized organizing pneumonia are nonspecific, and this unusual
      entity is difficult to differentiate from a primary or metastatic tumor. Surgical
      resection allows both diagnosis and cure. However, considering the benignity of
      the lesion and the efficacy of steroids, major pulmonary resections should be
      avoided.

PMID- 17532377
TI  - Segmental laryngotracheal and tracheal resection for invasive thyroid carcinoma.
AB  - BACKGROUND: Laryngotracheal invasion worsens prognosis in patients with thyroid
      carcinoma. The extent of resection is controversial. METHODS: We performed a
      retrospective study of patients with thyroid carcinoma and invasion of the larynx
      or trachea between 1964 and 2005. RESULTS: Eighty-two patients, mean age 64 years
      and 50% female, underwent segmental airway resection. Differentiated carcinoma
      was present in 76% (62 of 82 patients), prior tracheal "shave" procedures in 40%
      (33 of 82 patients), transmural invasion in 58% (48 of 82 patients), and
      preoperative vocal cord paralysis in 35% (29 of 82 patients). There were 29
      tracheal and 40 laryngotracheal resections (reconstruction group: 69 patients); 5
      underwent laryngectomy, 7 cervical exenteration, and 1 tracheal resection after
      exenteration (salvage group: 13 patients). Operative mortality was 1.2% (1 of 82
      patients) and anastomotic dehiscence 4.3% (3 of 69 patients). Tracheostomy was
      permanent in 4.3% (3 of 69 patients). Mean follow-up was 6.1 years. After
      reconstruction, mean survival was 9.4 years and 10-year survival was 40%; after
      salvage, these were 5.6 years and 15%, respectively. In differentiated carcinoma,
      thyroidectomy, immediate shave procedure, and delayed (mean, 67 months) resection
      of airway recurrence in 15 patients resulted in overall and disease-free survival
      of 13.1 and 5.1 years, respectively, compared with 17.9 and 14.6 years,
      respectively, after thyroidectomy and early airway resection in 11 patients.
      Airway symptoms, metastases at presentation, recurrent disease, and salvage
      operation were associated with decreased survival; airway resection early after
      thyroidectomy, complete resection, and well-differentiated tumors were associated
      with improved prognosis. CONCLUSIONS: Segmental airway resection for invasive
      thyroid cancer is safe, preserves the voice, and relieves airway obstruction.
      Complete resection of laryngeal and tracheal invasion during or early after
      thyroidectomy is associated with improved survival.

PMID- 17532378
TI  - Management of iatrogenic tracheobronchial injuries: a retrospective analysis of
      29 cases.
AB  - BACKGROUND: Tracheobronchial injuries are rare but potentially life-threatening
      complications of endotracheal intubations or endobronchial interventions. This
      retrospective analysis discusses the criteria for the operative and nonoperative
      management of tracheal lacerations. METHODS: From July 1996 to June 2006, 29
      patients with iatrogenic tracheobronchial injuries were diagnosed at our
      institution. The injury occurred during single-lumen tube intubation in 14
      patients and during double-lumen tube intubation in 2 patients. Two ruptures were
      diagnosed after surgical tracheostomy, eight after dilational percutaneous
      tracheostomy, and three after interventional bronchoscopy. RESULTS: The
      lacerations in 11 patients were superficial or were sufficiently covered by the
      esophagus, and they underwent conservative management. Bronchoscopy revealed
      healing per primam in every case. Surgical repair was done in 18 patients (62%).
      The transtracheal approach was used for repair in 7 patients; a right-sided
      posterolateral thoracotomy was performed in 11 patients with lacerations
      affecting the lower third of the trachea. Three surgical patients died from
      causes unrelated to the tracheal injury. No clinically evident mediastinitis or
      postoperative tracheobronchial stenosis was observed. CONCLUSIONS: The decision
      for operative or nonoperative treatment of iatrogenic tracheobronchial
      lacerations is determined by the ventilating situation and the local extent of
      the injury. Nonoperative management of iatrogenic tracheobronchial injuries may
      be a save option in patients with uncomplicated ventilation, superficial or
      sufficiently covered tears, and moderate and nonprogressive emphysema. Immediate
      surgical repair remains warranted in those patients who require mechanical
      ventilation that cannot be delivered past the laceration.

PMID- 17532379
TI  - Video-assisted thoracoscopic surgery is more favorable than thoracotomy for
      resection of clinical stage I non-small cell lung cancer.
AB  - BACKGROUND: Lobectomy for patients with clinical stage I non-small cell lung
      cancer (NSCLC) can be performed by thoracotomy or by video-assisted thoracoscopic
      surgery (VATS). We compared the operative characteristics and postoperative
      course for patients with clinical stage I NSCLC who underwent lobectomy by VATS
      or thoracotomy. METHODS: We retrospectively reviewed the charts of all patients
      undergoing lobectomy for clinical stage I NSCLC from January 1, 1998, through
      June 30, 2005. RESULTS: We performed 147 lobectomies (88 thoracotomy, 59 VATS) in
      147 patients with clinical stage I NSCLC. Patient demographics were similar
      between groups; however, VATS patients had more hypertension (p = 0.0114),
      chronic renal insufficiency (p = 0.0479), and previous malignancies (p = 0.0086).
      The two groups did not differ in pathologic stage, tumor size, histologic
      results, or number of positive nodes. More total nodes were identified in
      thoracotomy patients (p = 0.0001), and they had a shorter intensive care unit
      stay (p = 0.0224). VATS patients had significantly less postoperative pneumonia
      (p = 0.0023). VATS patients trended toward fewer chest tube days and a shorter
      hospital length of stay. The two groups did not differ in operative time, blood
      loss, atrial fibrillation, or number of ventilator days. Median survival between
      the cohorts was similar (>7.9 years thoracotomy versus >4.6 years VATS, log-rank
      p = 0.6939). CONCLUSIONS: Patients undergoing VATS lobectomy for clinical stage I
      NSCLC, despite having more comorbidities, had fewer postoperative complications.
      The approaches are equivalent in operative time, blood loss, length of stay, and
      survival rate. Compared with thoracotomy, VATS lobectomy for patients with
      clinical stage I NSCLC appears to be a less morbid operation.

PMID- 17532380
TI  - Surgical techniques and results for partial or circumferential sleeve resection
      of the pulmonary artery for patients with non-small cell lung cancer.
AB  - BACKGROUND: We assessed our experience with partial or circumferential resection
      of the pulmonary artery during lobectomy. METHODS: We retrospectively reviewed a
      prospective electronic database of patients who underwent pulmonary artery
      resection. The technique used was an R0 resection with end-to-end anastomosis
      only if needed, distal control of the pulmonary artery by clamping the vein (not
      the artery), and no postoperative anticoagulation. RESULTS: Between October 1998
      and June 6, 2006, 42 (3.2%) of 1328 patients who underwent lobectomy performed by
      one surgeon required resection of the pulmonary artery (38 partial, 4
      circumferential) to achieve a margin-negative resection and avoid pneumonectomy.
      Of these, 41 had non-small cell lung cancer, and 23 (55%) had neoadjuvant
      chemoradiotherapy (median dose of 60 Gy). Right upper lobectomy was performed in
      2 patients and a left upper lobectomy in 40. A negative bronchial and vascular
      margin was achieved in all. Morbidity occurred in 11 patients (atrial
      fibrillation in 6) and left recurrent laryngeal neurapraxia in 2. Aspiration
      resulted in one operative death. Follow-up (median, 48 months) showed no local
      recurrence on the pulmonary artery and normal blood flow through it. Five-year
      survival was 60%. CONCLUSIONS: Pulmonary artery resection and reconstruction to
      avoid pneumonectomy can be performed safely, even in a highly irradiated field.
      Clamping of the remaining pulmonary vein for distal control is safe and affords
      more room. Circumferential resection with end-to-end anastomosis of the pulmonary
      artery is rarely required. Partial resection is safe, does not impede blood flow,
      and does not compromise local recurrence rates. Postoperative anticoagulation is
      not needed.

PMID- 17532381
TI  - Transxiphoid hand-assisted videothoracoscopic surgery.
AB  - BACKGROUND: We have performed transxiphoid hand-assisted videothoracoscopy since
      1995 to allow manual palpation in bilateral lung metastasectomy. This approach
      was extended to other thoracoscopic procedures requiring a handport. No extensive
      report about early and late results has yet been published. METHODS: We
      retrospectively reviewed the first 100 consecutive patients undergoing
      transxiphoid hand-assisted videothoracoscopy. Acute and chronic postoperative
      pain, respiratory function, patient's satisfaction score (1 to 5), quality of
      life (Short Form-36), and survival rate were evaluated. RESULTS: Seventy-four
      patients had lung metastases, 5 had primary lung cancers, 16 had benign nodules,
      and 5 had Morgani's hernia. Five patients needed conversion to thoracotomy,
      whereas 7 successfully underwent a second transxiphoid operation. Sixty-five
      metastatic patients were bilaterally explored, 44 were without radiologic
      evidence of contralateral lesions, discovering 23 occult metastases and 10
      patients with occult contralateral disease. A total of 207 minimal resections and
      11 lobectomies were performed. Mean operative time was 103 +/- 35 minutes. We had
      no intraoperative mortality or major complications. Thirty-day postoperative
      morbidity documented arrhythmia (n = 4) and acute pneumonia (n = 4). Visual
      Analogue Scale pain, C-reactive protein, fibrinogen, and serum interleukin-6, -8,
      and -10 normalized within 72 hours. Respiratory function and most of the Short
      Form-36 domains recovered within 3 months. Six-month mean patient satisfaction
      score was 4.0 +/- 0.8. Three- and 5-year survival rates for metastatic patients
      were 52% and 43%, respectively. Mean disease-free interval was 12 +/- 5.8 months.
      CONCLUSIONS: Transxiphoid hand-assisted videothoracoscopy proved a good
      alternative to conventional approaches, and provided rapid recovery without
      affecting the survival rate in those patients with metastatic lesions. We
      recommend it whenever a handport during video-assisted procedure is required.

PMID- 17532382
TI  - Invited commentary.

PMID- 17532383
TI  - Cardiac function and position more than 5 years after pneumonectomy.
AB  - BACKGROUND: Pneumonectomy not only reduces the pulmonary vascular bed but also
      changes the position of the heart and large vessels, which may affect the
      function of the heart. We investigated long-term effects of pneumonectomy on
      right ventricular (RV) and left ventricular (LV) function and whether this
      function is influenced by the side of pneumonectomy or the migration of the heart
      to its new position. METHODS: In 15 patients who underwent pneumonectomy and
      survived for more than 5 years, we evaluated by dynamic magnetic resonance
      imaging the function of the RV and LV and the position of the heart within the
      thorax. RESULTS: Long-term effect of pneumonectomy on the position of the heart
      is characterized by a lateral shift after right-sided pneumonectomy and rotation
      of the heart after left-sided pneumonectomy. Postoperatively, heart rate was high
      (p = 0.006) and stroke volume was low (p = 0.001), compared with the reference
      values, indicating impaired cardiac function. Patients after right-sided
      pneumonectomy had an abnormal low RV end-diastolic volume of 99 +/- 29 mL
      together with a normal LV function. No signs of RV hypertrophy were found. In
      left-sided pneumonectomy patients, RV volumes were normal whereas LV ejection
      fraction was abnormally low. CONCLUSIONS: The long-term effects of pneumonectomy
      on the position of the heart are characterized by a lateral shift in patients
      after right-sided pneumonectomy and rotation of the heart in patients after left
      sided pneumonectomy. Overall, cardiac function in long-term survivors after
      pneumonectomy is compromised, and might be explained by the altered position of
      the heart.

PMID- 17532384
TI  - Invited commentary.

PMID- 17532385
TI  - Transhiatal esophagectomy for distal and cardia cancers: implications of a
      positive gastric margin.
AB  - BACKGROUND: A common operation for cancer of the esophagus and cardia consists of
      transhiatal esophagectomy, proximal gastrectomy, and a cervical esophagogastric
      anastomosis. The oncologic adequacy of dividing the stomach 4 to 6 cm distal to
      palpable tumor is not well documented, and when a positive gastric margin is
      present on the final pathologic analysis, the appropriate management is not
      established. This study was undertaken to determine the incidence of a positive
      gastric margin in these patients and the impact of adjuvant treatment. METHODS: A
      retrospective review was performed of 1044 patients undergoing transhiatal
      esophagectomy for adenocarcinoma of the distal esophagus or cardia. Twenty (1.9%)
      had a positive gastric margin on final the pathologic evaluation and met
      inclusion criteria for this study. RESULTS: Nine patients (45%) received adjuvant
      therapy consisting of radiation in 3, chemotherapy in 4, or both in 2. Their
      average postoperative survival was 477 days, compared with 455 days in those not
      receiving adjuvant therapy (p = 0.898). Local tumor recurrence developed in 1
      patient (11%) in the treatment group and in 3 (27%) in the no treatment group (p
      = 0.386). CONCLUSIONS: A transhiatal esophagectomy and proximal gastrectomy for
      carcinoma of the distal esophagus and cardia, dividing the stomach 4 to 6 cm from
      palpable tumor, provides a negative gastric margin in 98% of patients. In the few
      patients who have a positive gastric margin, 80% die with distant metastases,
      which would not be influenced by more extensive gastric resection, and in about
      20%, local tumor recurrence develops in the intrathoracic stomach, seldom causing
      dysphagia. Adjuvant therapy for a positive gastric margin neither improves
      survival nor reduces local tumor recurrence.

PMID- 17532386
TI  - Endoscopic ultrasound compared with laparoscopy for staging esophageal cancer.
AB  - BACKGROUND: Endoscopic ultrasonography (EUS) is an accurate modality for
      locoregional staging of esophageal cancer. Given an increasing prevalence of
      distal esophageal adenocarcinoma, some centers employ laparoscopic staging (LS)
      in addition to noninvasive staging methods. We sought to compare EUS and LS for
      nodal staging in patients with esophageal cancer. METHODS: All newly diagnosed,
      EUS-staged esophageal cancer cases during an 18-month period were reviewed.
      Patients who underwent both EUS and LS comprised the study cohort; EUS records,
      operative notes, and pathology reports were reviewed. Inability to pass the
      radial echoendoscope through the malignant stricture despite dilation was
      considered an incomplete EUS examination. RESULTS: Forty-seven patients were
      identified who underwent both modalities for staging; of these, 70% had complete
      EUS evaluation. For nodal staging, EUS-fine-needle aspiration was 90% accurate as
      compared with LS. Overall, staging accuracy of EUS compared with LS was 72%.
      Accuracy was 76% for patients with complete EUS staging compared with 64% for
      patients with incomplete EUS examinations. Staging differences were mostly
      reflected in distant metastases detected at LS (17%). CONCLUSIONS: Endoscopic
      ultrasonography is nearly as accurate as LS in nodal staging for esophageal
      cancer. The value of LS is accurate abdominal nodal staging and detection of
      occult distant metastases. Laparoscopic staging should, therefore, be
      incorporated into staging algorithms for neoadjuvant protocols. In the absence of
      preoperative therapy, LS should be performed at the time of planned
      esophagectomy. In those without occult metastases, curative resection may be
      attempted.

PMID- 17532387
TI  - Esophageal stent placement for the treatment of iatrogenic intrathoracic
      esophageal perforation.
AB  - BACKGROUND: Iatrogenic esophageal perforation after endoscopy or surgery can be a
      devastating event. Traditional therapy has most often consisted of operative
      repair of the esophagus. This investigation summarizes our experiences treating
      iatrogenic intrathoracic perforations of the esophagus using an occlusive
      removable esophageal stent. METHODS: Over a 24-month period, patients found to
      have an iatrogenic intrathoracic esophageal perforation at a tertiary care
      medical center were offered endoluminal esophageal stent placement instead of
      operative repair of the esophagus as initial therapy. Excluded were patients with
      an esophageal malignancy or a chronic esophageal fistula. Silicone-coated stents
      were placed endoscopically utilizing general anesthesia and fluoroscopy. Adequate
      drainage of infected areas was also simultaneously achieved. Leak occlusion was
      confirmed by esophagram. Patients were followed until their stent was removed and
      their esophageal leak had resolved. RESULTS: Seventeen patients had 18 esophageal
      stents placed for acute perforations of the esophagus after endoscopy (8) or
      surgery (9) during the study period. Associated endoscopic (13) or surgical
      procedures (7) were performed simultaneously in all 17 patients. Leak occlusion
      occurred in 16 patients (94%) as confirmed by esophagram. Fourteen patients (82%)
      were able to initiate oral nutrition within 72 hours of stent placement. One
      patient (6%) experienced a continued leak after stent placement and underwent
      operative repair. Stent migration requiring repositioning (2) or replacement (2)
      occurred in 3 patients (18%). All stents were removed at a mean of 52 +/- 20 days
      after placement. Hospital length of stay for patients treated with esophageal
      stent placement was 8 +/- 9 days (median, 5). CONCLUSIONS: Endoluminal esophageal
      stent placement is an effective method for the treatment of acute, iatrogenic
      perforations of the intrathoracic esophagus. These stents result in rapid leak
      occlusion, provide the opportunity for early oral nutrition, may significantly
      reduce hospital length of stay, are removable, and avoid the potential morbidity
      of operative repair.

PMID- 17532388
TI  - Surgery of left ventricular aneurysm: a meta-analysis of early outcomes following
      different reconstruction techniques.
AB  - BACKGROUND: The purpose of this study is to assess the effects of linear and
      geometric left ventricular aneurysm reconstruction on early postoperative
      outcomes. METHODS: A search of computerized databases supplemented with manual
      bibliographic review was performed for all peer-reviewed English language
      publications concerning randomized and nonrandomized studies reporting the
      results of left ventricular reconstruction after both linear and geometric
      reconstruction techniques. Meta-analyses of several short-term outcomes were
      performed. RESULTS: No randomized trial was identified. Eighteen nonrandomized
      trials were found with a total of 1,814 and 803 patients who underwent linear and
      geometric reconstruction, respectively. Meta-analysis of all studies (n = 18)
      revealed an increased risk of in-hospital death for patients undergoing linear
      reconstruction (relative risk = 1.59, 95% confidence interval: 1.12 to 2.26, p =
      0.01). The subanalysis of studies in which linear reconstruction was adopted
      mainly in the first period of time, and geometric reconstruction was adopted in a
      later phase, still showed a significant advantage in terms of in-hospital
      mortality for patients undergoing geometric reconstruction (n = 11 studies,
      relative risk = 1.89, 95% confidence interval: 1.22 to 2.93, p = 0.004). By
      contrast, when the two surgical approaches were carried out in the same time lag,
      there was no difference between linear and geometric reconstruction techniques (n
      = 7 studies, relative risk = 1.04, 95% confidence interval: 0.57 to 1.92, p =
      0.89). No differences in the other outcomes of interest were observed.
      CONCLUSIONS: The advantage for geometric reconstruction techniques in terms of in
      hospital mortality shown in some studies can be an effect of learning curve or of
      improvement over time in management of these difficult patients. Further studies
      are required to clarify this issue.

PMID- 17532389
TI  - Invited commentary.

PMID- 17532390
TI  - Impact of lateral wall myocardial infarction on outcomes after surgical
      ventricular restoration.
AB  - BACKGROUND: Surgical ventricular restoration (SVR) attempts to reverse negative
      ventricular remodeling after anterior myocardial infarction (MI). However, the
      impact of lateral wall MI (LMI) on SVR outcomes is unknown. METHODS: We
      retrospectively reviewed SVR patients between January 2002 and December 2005.
      Patients were grouped into those with and without LMI. Lateral wall myocardial
      infarction patients were further subdivided into those with anterior-lateral and
      anterior-inferior-lateral MI. Extent of LMI was assessed intraoperatively as less
      than 25%, 25% to 49%, 50% to 75%, and more than 75% of the lateral wall. Follow
      up was 100%. RESULTS: Seventy-eight patients underwent SVR; all had anterior MI.
      Forty-one percent (32 of 78) had LMI; 19% (6 of 32) had anterior-lateral MI; and
      81% (26 of 32) had anterior-inferior-lateral MI. The remaining 59% (46 of 78)
      comprised the no-LMI group. Among LMI patients, 6% (2 of 32) had more than 75%
      involvement of the lateral wall. Lateral wall myocardial infarction patients were
      more likely to be New York Heart Association (NYHA) class IV preoperatively.
      There were 2 operative deaths in the LMI group. Surgical ventricular restoration
      significantly improved ejection fraction and end-systolic volume index for
      patients with and without LMI. Sixty-three percent of patients (20 of 32) with
      LMI and 83% of patients (38 of 46) without LMI improved to NYHA class I/II at
      follow-up. Three-year Kaplan-Meier survival for LMI patients was 67%, which
      trended toward a decreased survival versus patients without LMI (85%; p = 0.18).
      Three-year Kaplan-Meier survival for anterior-lateral MI patients was 100%, and
      for anterior-inferior-lateral MI patients, it was 60%. Lateral wall myocardial
      infarction involving >50% of the lateral wall was a significant predictor of
      mortality (odds ratio = 8.3, 95% confidence interval: 1.3 to 54.1, p = 0.03).
      CONCLUSIONS: Cardiac function is improved after SVR for patients with and without
      LMI. However, anterior-inferior-lateral MI and LMI involving 50% or more of the
      lateral wall may predict mortality. Our results should prompt further
      investigation to determine the role of SVR for patients with LMI.

PMID- 17532391
TI  - Predicting operative mortality after surgery for ischemic cardiomyopathy.
AB  - BACKGROUND: Ischemic cardiomyopathy accounts for as many as 70% of cases of heart
      failure with no clear algorithm for the treatment. We assessed the operative
      risks and mortality of various surgical options: coronary artery bypass grafting
      (CABG), CABG and mitral valve repair (CABG/MVR), and left ventricular remodeling
      (LVR) with or without CABG. We hypothesized that additional procedures increased
      the operative risk. We determined whether preoperative variables (eg, urgency of
      operation) impacted the surgical outcome. METHODS: A retrospective analysis of
      University of Virginia patients from January 2000 until September 2006 was
      undertaken. Patients with CABG and an ejection fraction less than 35%, ischemic
      mitral regurgitation by operative characterization, and patients with LVR were
      identified. The Society of Thoracic Surgeons database risks, complications, and
      outcomes as well as degree of revascularization, quality of targets, and type of
      additional procedures were analyzed. Incomplete revascularization was defined as
      a planned bypass not performed. Poor targets were defined as per the operative
      note. RESULTS: In all, 382 patients were identified (220 CABG, 97 CABG/MVR, and
      65 LVR). The overall operative mortality was 7.9%. Mortality was 9.1% for CABG,
      8.2% for CABG/MVR, and 3.1% for LVR. Preoperative risk factors for mortality
      included diabetes mellitus (p = 0.05), previous cerebrovascular disease (p =
      0.05), and chronic renal dysfunction (p = 0.03). Patients with emergency
      operations had a significantly increased mortality (p < 0.001) as did patients
      with intra-aortic balloon pumps (p = 0.015). CONCLUSIONS: Additional procedures
      such as MVR or LVR did not add to the operative risk of CABG for ischemic
      cardiomyopathy. Only preoperative comorbidities and emergency operations
      increased operative mortality.

PMID- 17532392
TI  - Long-term consequences of postoperative heart failure after surgery for aortic
      stenosis compared with coronary surgery.
AB  - BACKGROUND: Although postoperative heart failure is a major determinant of
      operative mortality in cardiac surgery it has received little attention in the
      literature, and long-term consequences remain to be addressed. Therefore, the
      impact of postoperative heart failure on long-term survival in relation to other
      risk factors was studied. METHODS: All patients undergoing aortic valve
      replacement (AVR) for aortic stenosis from 1995 through 2000 in the southeast
      region of Sweden (n = 398) were compared with a cohort, matched for age and sex,
      undergoing coronary artery bypass grafting (CABG [n = 398]). Risk factors for 5
      year mortality were analyzed. RESULTS: Forty-five AVR and 47 CABG patients
      required treatment for postoperative heart failure. Thirty-day, 1-year, and 5
      year mortality in patients with and without postoperative heart failure after AVR
      were 6.7% versus 1.4% (p = 0.05), 8.9% versus 4.0% (p = 0.13), and 42.2% versus
      14.2% (p < 0.0001) respectively. Corresponding results in the CABG group were
      21.3% versus 1.1% (p < 0.0001), 25.5% versus 3.1% (p < 0.0001), and 36.2% versus
      11.1% (p = 0.0015). Postoperative heart failure, preoperative renal dysfunction,
      procedure-associated stroke, body mass index less than 19 kg/m2, older age,
      preoperative atrial fibrillation, and preoperative anemia turned out as
      independent risk factors for 5-year mortality after AVR. In the CABG group,
      postoperative heart failure, diabetes mellitus, older age, and procedure
      associated stroke emerged as independent risk factor for 5-year mortality.
      CONCLUSIONS: Postoperative heart failure was associated with high early mortality
      after CABG whereas the grave consequences of postoperative heart failure after
      AVR for aortic stenosis became evident only with time.

PMID- 17532393
TI  - Aortic annular enlargement during aortic valve replacement: improving results
      with time.
AB  - BACKGROUND: Enlargement of the aortic annulus during aortic valve replacement
      permits insertion of a larger prosthetic valve. Previous reports suggest patch
      enlargement of the aortic annulus increases operative morbidity and mortality
      during aortic valve replacement. We compared outcomes for this procedure in a
      contemporary group of patients with those operated on during an earlier era, to
      determine whether aortic annular enlargement is still associated with worse
      outcomes. METHODS: We reviewed prospectively gathered data on all patients
      undergoing aortic valve replacement and aortic annular enlargement at our
      institution from 1995 to 2005 (n = 669). We compared patient outcomes from two
      consecutive time periods: 1995 through 2000 (n = 360) versus 2001 through 2005 (n
      = 309). Propensity matching adjusted for baseline differences in a secondary
      analysis. RESULTS: Operative mortality was significantly lower in the more recent
      surgical group (2.9% versus 7.2%; p = 0.013). The rates of perioperative
      myocardial infarction (1.9% versus 1.1%; p = 0.4), stroke (2.9% versus 3.3%; p =
      0.8), and pacemaker implantation (9.1% versus 12.5%; p = 0.16) were similar for
      both groups (2001 through 2005 versus 1995 through 2000, respectively). The
      earlier group of patients had a higher prevalence of congestive heart failure,
      syncope, angina, New York Heart Association class III or IV symptoms, chronic
      obstructive pulmonary disease, mitral valve disease, and previous cardiac
      surgery. After adjusting for these baseline differences with propensity matching,
      the risk of perioperative death remained lower in the contemporary group (3%
      versus 7.5%; p = 0.04). CONCLUSIONS: Enlargement of the aortic annulus in the
      modern era is a safe adjunct to aortic valve replacement, and should be
      considered in selected patients to avoid patient-prosthesis mismatch.

PMID- 17532394
TI  - Aortic valve replacement with 17-mm St. Jude Medical prostheses for a small
      aortic root in elderly patients.
AB  - BACKGROUND: There are few reports about the optimal prosthesis for elderly
      patients who have small aortic roots with an aortic annular size of less than 19
      mm. METHODS: From October 2004 to October 2006, 11 women aged 70 years or older
      (mean age, 74.9 +/- 3.5 years) underwent aortic valve replacement with a 17-mm
      Regent prosthesis (St. Jude Medical, St. Paul, MN), with the size determined
      using the manufacturer's sizer. Clinical status and the results of preoperative
      and postoperative echocardiography were evaluated. RESULTS: The patients had a
      mean body surface area of 1.33 +/- 0.13 m2. Preoperative average New York Heart
      Association (NYHA) functional class was 2.5 +/- 0.7. Preoperative
      echocardiography showed a mean indexed effective orifice area of 0.33 +/- 0.14
      cm2/m2 and a left ventricular mass index of 175 +/- 63 g/m2. Seven patients
      underwent associated procedures. Postoperative ventilation time was 14 +/- 5.6
      hours, and the intensive care unit stay was 1.0 +/- 0.4 days. No patients died
      perioperatively. The NYHA functional class improved to class I in 9 patients. No
      obstruction of valve opening was observed. A significant increase in the mean
      indexed effective orifice area (0.87 +/- 0.10 cm2/m2) and regression of left
      ventricular mass index were found (114 +/- 46 cm2/m2) on postoperative
      echocardiography. CONCLUSIONS: Aortic valve replacement in elderly patients with
      small aortic roots (less than 19 mm) using a 17-mm Regent prosthesis showed
      satisfactory clinical and hemodynamic results.

PMID- 17532395
TI  - Carpentier-Edwards Perimount Magna valve versus Medtronic Hancock II: a matched
      hemodynamic comparison.
AB  - BACKGROUND: The Perimount Magna valve (Edwards Lifesciences, Irvine, CA) was
      designed to minimize the amount of obstruction to blood flow across the valve. We
      compared hemodynamic performance of the Perimount Magna valve with the Hancock II
      valve (Medtronic, Minneapolis, MN), a second-generation porcine bioprosthesis
      with proven long-term results. METHODS: The 57 patients who received a Magna
      valve at our institution from 2003 to 2005 were matched 1:1 with 57 patients who
      received a Hancock II valve on variables known to affect hemodynamic
      measurements: size of implanted valve, age, sex, and body surface area. Early
      postoperative transthoracic echocardiography was performed in 100% of patients.
      RESULTS: In addition to the matched variables, patients in both groups were
      similar for all measured preoperative characteristics and perioperative clinical
      outcomes. One week postoperatively, Magna patients had significantly lower peak
      (22.1 +/- 7.4 mm Hg versus 32.3 +/- 15.1 mm Hg) and mean transvalvular gradients
      (10.4 +/- 4.0 mm Hg versus 18.5 +/- 15.5 mm Hg, both p < 0.001). The Magna group
      also had a trend towards a larger effective orifice area (1.40 +/- 0.24 cm2
      versus 1.29 +/- 0.34 cm2, p = 0.07), despite a similar left ventricular outflow
      tract diameter (2.0 +/- 0.2 cm versus 2.0 +/- 0.1 cm, p = 0.7). Patient
      prosthesis mismatch, as defined by measured effective orifice area of less than
      0.65 cm2/m2, was significantly less common in the Magna group (30% versus 52%, p
      = 0.02). CONCLUSIONS: The Magna valve has more favorable early postoperative
      hemodynamics than the Hancock II valve. Further studies should be performed
      comparing the Magna valve to newer-generation, low-profile porcine valves.

PMID- 17532396
TI  - Invited commentary.

PMID- 17532397
TI  - Efficacy and safety of aprotinin use for reoperative valvular surgery.
AB  - BACKGROUND: Preservation of the hemostatic system during cardiac surgery is a
      main concern, primarily after repeated cardiac operations. METHODS: We compared
      the outcomes of adult patients undergoing isolated reoperative valvular surgery
      receiving full-dose of aprotinin (redo group, n = 70) with patients experiencing
      primary isolated valvular surgery not receiving aprotinin (primary group, n =
      135). RESULTS: The mean age was lower in the redo group (45 +/- 14 years vs 50 +/
      17 years, p = 0.036). The redo group had more female patients (73% vs 51%, p =
      0.003), patients in functional class IV (15% vs 4% p = 0.009), and patients with
      chronic atrial fibrillation (48% vs 24%, p = 0.001). The cardiopulmonary bypass
      duration was longer in the redo group (119 +/- 50 minutes vs 103 +/- 41 minutes,
      p = 0.014). However, the blood loss was significantly lower (300 +/- 279 mL vs
      776 +/- 584 mL, p = 0.001) and fewer patients needed transfusions (3.0% vs 13%, p
      = 0.023) in the redo group. The postoperative morbidity was similar in both
      groups. The postoperative in-hospital mortality was 7% in the primary group and
      10% in the redo group (p = 0.419). Factors associated with postoperative in
      hospital mortality were the following: age greater than 60 years (p = 0.040, odds
      ratio [OR] 3.0), New York Heart Association class IV (p = 0.022, OR 5.0),
      preoperative critical state (p < 0.001, OR 12), emergent operation (p = 0.012, OR
      7.0), endocarditis (p = 0.004, OR 10.0), and reoperation due to mechanical mitral
      prosthesis dysfunction (p = 0.009, OR 7). CONCLUSIONS: The mortality and
      morbidity in redo valve surgery with aprotinin administration was comparable with
      primary valve surgery without aprotinin. Bleeding and transfusion requirements
      were significantly lower in redo patients receiving aprotinin.

PMID- 17532398
TI  - Postconditioning the human heart with adenosine in heart valve replacement
      surgery.
AB  - BACKGROUND: The effect of adenosine postconditioning on myocardial protection in
      cardiac surgery remains uncertain. The present study evaluated the safety,
      feasibility, and beneficial effect of adenosine postconditioning as an adjunct to
      predominantly used cold-blood cardioplegic myocardial protection method in the
      setting of heart valve replacement operations. METHODS: Sixty patients with
      rheumatic heart valve disease undergoing heart valve replacement operations were
      randomized to an adenosine (1.5 mg/kg) or saline (as control) bolus injection
      through an arterial catheter immediately after the aorta cross-clamp was removed.
      The surgical indications were similar in both groups, and heart valve replacement
      was successful in all patients. RESULTS: The extubation time and postoperative
      hospital time were similar in both groups. Compared with the control group,
      however, the inotrope scores in the intensive care unit (ICU) were much lower (p
      < 0.01), and the ICU time was significantly shorter (p < 0.05) in adenosine
      group. More important, cardiac troponin I release was less in the adenosine
      group, especially at 12 and 24 hours after reperfusion (p < 0.01), and total
      cardiac troponin I release estimated with the area under curve was also
      significantly reduced during the first 24 hours after reperfusion (p < 0.01).
      CONCLUSIONS: A 1.5-mg/kg bolus administration of adenosine through an arterial
      catheter immediately after the aorta cross-clamp is removed is feasible and well
      tolerated in patients undergoing heart valve replacement. An adenosine
      postconditioning adjunct to high potassium cold blood myocardial protection is
      related to less troponin I release, less inotropic drug use, and shorter ICU
      stay.

PMID- 17532399
TI  - Invited commentary.

PMID- 17532400
TI  - Treatment of endocarditis: a decade of experience.
AB  - BACKGROUND: Endocarditis represents a small proportion of cardiovascular disease
      but is associated with high mortality. Previous studies have reported a range of
      outcomes, and determinants of mortality remain poorly defined. METHODS: The goal
      of this retrospective study was to identify independent variables for early and
      late mortality in 364 consecutive patients with endocarditis over a 10-year
      period. RESULTS: The mean age of patients was 48.2 years, 35% had a history
      intravenous drug use, 19.8% were reoperative, and 93% had native valve
      endocarditis. Fever (68%) and fatigue (36%) were the most common presenting
      symptoms, and congestive heart failure (52%), embolization (45%), and
      uncontrolled sepsis (36%) were the most common indications for surgery. Overall
      survival at discharge, 1, 5, and 10 years was 87%, 76%, 55%, and 31%,
      respectively. Survival at discharge, 5, and 10 years was 91%, 69%, and 41% for
      surgical patients and 85%, 60%, and 31% for medically treated patients,
      respectively. Surgery was associated with improved short-term and long-term
      survival (p < 0.0.01). Independent predictors of early death were hemodynamic
      instability (p = 0.013) and age older than 55 years (p < 0.025). Medical
      treatment (p = 0.005), age older than 55 years (p = 0.032), institution (p <
      0.001), New York Heart Association functional class III or IV (p = 0.002), and
      hemodynamic instability (p = 0.044) were predictive of late death. CONCLUSIONS:
      Short-term and long-term mortality from endocarditis remains high, although
      surgically treated patients had improved survival. Differing outcomes from two
      geographically similar institutions highlight the limitations of extrapolating
      risk factors between disparate patient populations.

PMID- 17532401
TI  - Epidemiology and clinical outcomes of infective endocarditis in hemodialysis
      patients.
AB  - BACKGROUND: Infective endocarditis is one of the most serious complications of
      bacteremia in patients undergoing chronic hemodialysis and is more frequent than
      previously recognized. The aim of our study was to describe the clinical
      characteristics, outcome, and factors predicting mortality of infective
      endocarditis in hemodialysis patients. METHODS: In this retrospective review, all
      patients on chronic hemodialysis admitted to a 600-bed urban teaching hospital
      with infective endocarditis over a 15-year period (1990 to 2004), were identified
      using discharge codes. Modified Duke criteria were retrospectively applied, and
      patients fulfilling the criteria for definite endocarditis were included in the
      study. RESULTS: Sixty-nine patients on hemodialysis with definite endocarditis
      were identified. The predominant type of vascular access was double-lumen
      catheter (66.7%). The mean duration of dialysis was 37 +/- 32 months. The
      predominant organism was Staphylococcus aureus (57.9%), of which 57.5% were
      methicillin susceptible. The most frequently infected valve was mitral (49.3%),
      followed by aortic (21.7%) and tricuspid (10.1%) valves. The cardiac and
      neurologic complication rates were 40.6% and 37.7%, respectively. Fifteen
      patients underwent valvular heart surgery. The overall in-hospital mortality was
      49.3% (34 of 69). More patients who had surgery survived than patients who did
      not (12 of 15 versus 23 of 54; p = 0.018, odds ratio = 5.39, 95% confidence
      interval: 1.3 to 17.6). On logistic regression, valve surgery was the only
      independent factor predicting survival (p = 0.023). CONCLUSIONS: The prognosis of
      infective endocarditis in hemodialysis patients is poor, with surgery serving as
      an independent predictor of survival.

PMID- 17532402
TI  - Invited commentary.

PMID- 17532403
TI  - The topography of aortic atherosclerosis enhances its precision as a predictor of
      stroke.
AB  - BACKGROUND: Atherosclerosis of the thoracic aorta is an independent risk factor
      for stroke after cardiac surgery. No attention had so far been paid to its
      topography. The relationship between the topography of aortic atherosclerosis and
      stroke was studied in patients admitted for coronary surgery. METHODS: The extent
      and location of atherosclerosis in the ascending aorta and arch was assessed
      intraoperatively with epiaortic ultrasound and transesophageal echocardiography
      in 611 consecutive patients. They were followed for 5.5 +/- 1.7 years (mean +/-
      SE), amounting to 3,358 patient-years. RESULTS: The incidence of early
      postoperative (<30-day) stroke was 6.4% in patients with atherosclerosis of the
      ascending aorta and 1.5% in those without (p = 0.004). The five-year stroke-free
      survival rates (>30 days after the operation) for patients without aortic
      disease, with less than 50%, and with greater than 50% of the ascending aorta
      affected, were 95.3 +/- 0.9%, 91.8 +/- 2.1%, and 65.0 +/- 14.6%, respectively (p
      < 0.0001). CONCLUSIONS: Atherosclerosis of the ascending aorta stands out as a
      predictor of late stroke. High risk is predominantly linked to atheromas in its
      distal part and lesser curvature.

PMID- 17532404
TI  - Invited commentary.

PMID- 17532405
TI  - Does stenosis severity of native vessels influence bypass graft patency? A
      prospective fractional flow reserve-guided study.
AB  - BACKGROUND: After coronary bypass surgery, occlusion or narrowing of bypass
      grafts may occur over time. The present study prospectively evaluated the
      angiographic patency of bypass grafts after 1 year in relation to the
      preoperative angiographic and functionally severity of the coronary lesion
      assessed by fractional flow reserve measurement to test the hypothesis that
      grafting of less critical stenosis may be a risk factor for early dysfunction of
      the graft. METHODS: The study comprised 164 patients eligible for coronary artery
      bypass surgery who were not suitable for percutaneous intervention and with at
      least one intermediate lesion. Fractional flow reserve was measured in all
      lesions to be grafted to establish if a lesion was functionally significant. The
      surgeon was blinded to the results of these measurements. One year after surgery,
      coronary angiography was performed to establish bypass graft patency. RESULTS: At
      coronary angiography after 1 year, 8.9% of the bypass grafts on functionally
      significant lesions were occluded, and 21.4% of the bypass grafts on functionally
      nonsignificant lesions were occluded. There was no difference in angina class or
      repeat interventions between patients with or without occluded bypass grafts.
      CONCLUSIONS: The patency of bypass grafts on functionally significant lesions is
      significantly higher than the patency of bypass grafts on nonsignificant lesions;
      however, this finding has no clinical relevance because patients with patent or
      occluded bypass grafts on nonsignificant lesions did not experience an excess of
      angina or repeat interventions.

PMID- 17532406
TI  - Exclusive internal thoracic artery grafting in triple-vessel-disease patients:
      angiographic control.
AB  - BACKGROUND: The internal thoracic artery (ITA) is considered to be the conduit of
      choice for coronary artery bypass grafting surgery (CABG). In triple-vessel
      disease patients, CABG can be performed exclusively using both ITAs in a Y
      fashion with multiple sequential side-to-side coronary anastomoses. The aim of
      this prospective study was to evaluate by early postoperative angiographic
      control, the patency and particularly the quality of ITA grafts and coronary
      anastomoses in this configuration. METHODS: Between October 2002 and October
      2003, 92 triple-vessel-disease patients underwent CABG with this technique and
      consented to immediate postoperative angiographic control. The right ITA was
      divided at its origin and connected to the in-situ left ITA (ITA-Y anastomosis).
      The left ITA was anastomosed to anterior coronary arteries and the right ITA was
      anastomosed to lateral and inferior coronary arteries, for a total of 374
      coronary anastomoses (4.1 anastomoses per patient; range, 3 to 6). RESULTS: There
      was 1 hospital death by septic shock. Two patients were reoperated on for
      superficial wound infection. There was no postoperative myocardial infarction or
      stroke. On postoperative angiograms, all ITA-Y (92) and ITA-coronary anastomoses
      (374) were patent. Competition of flow in right ITA to the moderately stenosed
      right coronary artery was observed in 9 patients, and there were 4 distal ITA
      coronary stenoses, both without clinical consequences. CONCLUSIONS: In triple
      vessel-disease patients, this procedure allows CABG without increasing operative
      risk. ITA-Y anastomoses and multiple sequential side-to-side ITA-coronary
      anastomoses are safe to perform and demonstrate excellent patency and quality in
      early postoperative angiographic control, particularly when coronary artery
      stenoses are significant (>70%).

PMID- 17532407
TI  - Impact of residency status on perfusion times and outcomes for coronary artery
      bypass graft surgery.
AB  - BACKGROUND: A price of training residents in cardiothoracic surgery is often
      perceived to be a loss in intraoperative efficiencies, leading to prolonged
      cardiopulmonary bypass and perfusion time. Because these indicators are also
      thought to adversely affect operative outcome, we investigated the association
      between residency training status, perfusion times, and outcomes. METHODS: Using
      the Society of Thoracic Surgeons (STS) National Cardiac Database, we studied
      369,906 CABG patients undergoing isolated coronary artery bypass graft (CABG)
      procedures during January 2002 through June 2005. Participating institutions were
      stratified by residency versus nonresidency status and by perfusion time
      categories and analyzed for association with clinical outcomes. RESULTS: Overall,
      57 (10%) of 594 STS participants had a residency training program. Residency
      programs had longer mean cross-clamp and perfusion times than nonresidency
      programs, 73.10 versus 67.44 minutes and 104.75 versus 98.00 minutes,
      respectively (p < 0.0001 for both. Longer perfusion time was significantly
      associated with higher operative mortality at the patient level. Unadjusted
      mortality rates were, however, similar for patients at residency and nonresidency
      programs (2.30% versus 2.27%), with an adjusted odds ratio of 0.96 (95%
      confidence interval, 0.84 to 1.09). Although perfusion times have not changed
      significantly over time between residency and nonresidency programs, mortality
      rates have significantly improved over time at each. CONCLUSIONS: Residency
      programs have longer CABG perfusion times than nonresidency cardiothoracic
      surgery programs, but these differences are minor. Adjusted procedural outcomes
      at residency training programs are similar to those at nonresidency centers;
      thus, patients do not appear to be adversely impacted by the time costs of
      surgical training.

PMID- 17532408
TI  - Can the EuroSCORE predict the early and mid-term mortality after off-pump
      coronary artery bypass grafting?
AB  - BACKGROUND: This study evaluated the role of the European System for Cardiac
      Operative Risk Evaluation (EuroSCORE) in the prediction of early-term and mid
      term mortality in patients undergoing isolated off-pump coronary artery bypass
      grafting (OPCAB). METHODS: From January 2002 to August 2006, 757 consecutive
      patients underwent isolated OPCAB. The patients' operative risks were calculated
      according to the standard and logistic EuroSCORE models. The cohort was
      classified into four subgroups according to both EuroSCORE scales. To evaluate
      the predictability, the expected mortality was compared with the observed
      mortality. The receiver operating characteristic curves were plotted and
      calibration was assessed. Mean follow-up was 32.8 +/- 13.9 months. RESULTS: Ten
      (1.3%) in-hospital deaths occurred. The predicted total numbers of deaths by the
      EuroSCORE models were 34.2 (4.5%) for the standard EuroSCORE and 37.8 (5.0%) for
      the logistic EuroSCORE. The expected mortality rates were significantly higher
      than the observed mortality rates in all subgroups, except one. The area under
      curve (AUC) in in-hospital mortality was 0.72 for the standard EuroSCORE and 0.71
      for the logistic EuroSCORE, but the tests of calibration for both EuroSCORE
      models were significant. Mid-term mortality was 3.6%. The AUC curve in mid-term
      mortality was 0.71 for the standard or logistic EuroSCORE. The calibration in
      both EuroSCORE models for mid-term mortality was nonsignificant, indicating good
      calibration. CONCLUSIONS: Both EuroSCORE models overestimated the in-hospital
      mortality; however, both models showed good predictability for mid-term
      mortality. The EuroSCORE could be helpful in planning resource allocation and
      tailoring follow-up for patients undergoing isolated OPCAB.

PMID- 17532409
TI  - Absence of correlation between symptoms and rhythm in "symptomatic" atrial
      fibrillation.
AB  - BACKGROUND: Symptoms are widely used as a means of assessment and follow-up of
      patients with atrial fibrillation. This study assessed the correlation between
      symptoms and cardiac rhythm in patients being evaluated for operative therapy for
      atrial fibrillation. METHODS: Seven days of preoperative continuous outpatient
      home electrocardiographic monitoring was performed on 50 patients with
      symptomatic atrial fibrillation. Cardiac rhythm was continuously monitored
      automatically, while patients recorded their symptoms electronically.
      Correlations were then drawn between symptomatic events and actual rhythm, and
      between atrial fibrillation episodes and symptoms. RESULTS: Fifty patients (37
      men) with symptomatic atrial fibrillation were monitored for a combined 356 days
      (mean, 7.1 days). Patients were average age of 69 years old. Intermittent atrial
      fibrillation was reported by 36 patients, and 14 believed their atrial
      fibrillation was continuous. During monitoring, all patients had periods of both
      atrial fibrillation and normal sinus rhythm. Of the 552 documented episodes of
      atrial fibrillation, 467 (85%) were asymptomatic, and 85 (15%) episodes were
      symptomatic. Patients indicated that they experienced atrial fibrillation
      symptoms 163 times. Of the 163 symptomatic events, 85 (52%) were actual atrial
      fibrillation, 64 (42%) were sinus rhythm, and 14 (6%) were other rhythms. The
      ability of an individual patient to accurately identify atrial fibrillation
      ranged from 0% to 100%. CONCLUSIONS: Patient-reported symptoms of atrial
      fibrillation had poor correlation with actual rhythm. The lack of correlation
      between symptoms and rhythm underscores the importance of continuous home
      monitoring for accurately quantifying preoperative atrial fibrillation burden and
      for postoperative follow-up.

PMID- 17532410
TI  - Impact of perfusion strategy on neurologic recovery in acute type A aortic
      dissection.
AB  - BACKGROUND: The optimal perfusion strategy during surgery of acute type A aortic
      dissection is controversial. The purpose of this study was to determine the
      impact of retrograde cerebral perfusion during hypothermic circulatory arrest on
      short-term and long-term outcome in this specific patient population. METHODS:
      Between 1984 and 2005, 175 consecutive patients underwent repair of an acute type
      A dissection. Three different surgical approaches were used: aortic cross
      clamping without hypothermic circulatory arrest in 50 (29%), hypothermic
      circulatory arrest alone in 69 (39%), and hypothermic circulatory arrest with
      supplemental retrograde cerebral perfusion in 56 (32%). RESULTS: Operative
      mortality was 18% +/- 3% (+/- 70% confidence interval), and adverse outcomes
      (death or cerebrovascular accident) occurred in 21% +/- 3% of patients (p = 0.97
      between groups). Multivariate analysis identified valve replacement (p = 0.04),
      preoperative flow complications (p = 0.03), and non-Marfan syndrome (p = 0.04) as
      predictors of operative mortality. Intraoperative dissection (p < 0.001) and
      history of cerebrovascular disease (p = 0.02) were predictors for permanent
      neurologic deficit, and retrograde cerebral perfusion was shown to have a
      protective effect on transient neurologic deficits (p = 0.008). Kaplan-Meier
      survival was 75% +/- 3% at 1 year (131 patients at risk), 63% +/- 4% at 5 years
      (87 patients at risk), and 49% +/- 4% at 10 years (48 patients at risk) and was
      independent of surgical approach (p = 0.37). Long-term survival was diminished
      with increased age (p < 0.001), earlier operative year (p < 0.001), and coronary
      artery disease (p = 0.02). CONCLUSIONS: The current investigation suggests
      improved neurologic recovery with circulatory arrest and supplemental retrograde
      cerebral perfusion. Operative mortality and long-term survival were comparable
      among groups.

PMID- 17532411
TI  - Anatomy of spinal cord blood supply in the pig.
AB  - BACKGROUND: In a species as popular in research as the pig, little information is
      available concerning the blood supply and vascular anatomy of the spinal cord and
      comparability to humans. METHODS: To visualize vessels contributing to the blood
      supply of the spinal cord, x-ray digital subtraction angiography and vascular
      casting by injection of a polymerizing solution of methylmethacrylate were used.
      RESULTS: The pig has larger internal thoracic arteries and subscapular arteries
      than the human, providing extensive collateral flow to the lower body, which
      offers blood supply to the spinal cord through the collaterals. The pig has a
      fine-caliber vessel plexus providing blood to the neck area, from which flow will
      reach both the spinal cord and the base of the brain. The segmental thoracic and
      lumbar arteries are relatively small in pigs, and they almost all originate as a
      single branch from the aorta and divide after 3 to 4 mm. The segmental vessels
      show a clear diminution after 2 to 3 cm at the level of the vertebral bodies.
      Pigs show major differences in the anatomy of the aortic bifurcation compared
      with humans. The median sacral artery in pigs is a large-caliber vessel, of a
      size almost comparable to the common iliac artery, with an isolated single dorsal
      branch leading to the spinal cord. CONCLUSIONS: Documenting the anatomic
      differences in spinal cord blood supply between pigs and humans will aid in the
      planning of future experimental studies and in determining the clinical relevance
      of such studies.

PMID- 17532412
TI  - Comparison of survival in primary and repeat heart transplantation from 1987
      through 2004 in the United States.
AB  - BACKGROUND: The purpose of this study was to identify predictors for survival
      after primary and repeat heart transplantations, and to compare their survival.
      METHODS: The United Network for Organ Sharing database provided 20,787 primary
      heart transplants and 594 repeat heart transplants (for those patients who had
      previously undergone a primary heart transplant). Cox regression models were used
      to separately determine predictors of survival in primary and retransplant
      patients and to compare their survival distributions. Propensity score matching
      was then used to compare the survival between primary and retransplant patients
      adjusted for potential confounders. RESULTS: Similar predictors of survival were
      found for primary and retransplant patients. The overall increased risk of death
      was 71% higher for retransplant versus primary transplant patients. Propensity
      score analysis showed that, in patients with characteristics most similar to
      primary transplant patients, the increased risk of death was 133%; however, for
      patients with characteristics most like retransplant patients, the increased risk
      of death was only 34%. CONCLUSIONS: Survival after retransplantation is
      significantly reduced relative to survival after primary transplantation. The
      difference in survival between primary and repeat transplants is smallest among
      recipients who fit the profile of the typical repeat transplant patient. In
      general, these are younger patients with better functional status prior to
      listing, who received an organ from a younger donor.

PMID- 17532413
TI  - Endoscopic cardiac tumor resection.
AB  - BACKGROUND: The purpose of this study is to report our 9 years' experience with
      endoscopic cardiac tumor resection using the port access approach. METHODS: From
      March 1997 to December 2005, 27 patients (mean age, 56.2 +/- 16.9 years; 70%
      female) underwent endoscopic cardiac tumor resection using endocardiopulmonary
      bypass and endoaortic-balloon clamp technique. Nineteen (70%) patients presented
      in New York Heart Association class I, 4 patients presented with embolic stroke,
      and 4 patients presented with atrial arrhythmias. All patients underwent
      echocardiography on admission, intraoperatively, at discharge, and at follow-up
      evaluation. Eight patients additionally required mitral valve replacement (n =
      1), tricuspid valve replacement (n = 1), mitral valve repair (n = 2), mini-maze
      (n = 1), and closure of patent foramen ovale (n = 3). Mean follow-up was 3.4 +/-
      2.7 years. RESULTS: Mean endoaortic-balloon clamp and endocardiopulmonary bypass
      times were 68.8 +/- 30.8 minutes and 112.2 +/- 41.5 minutes, respectively. There
      were no conversions to sternotomy. Tumors resected were classified as left atrial
      myxoma (n = 20), right atrial myxoma (n = 3), lipoma (n = 1), intravenous
      leiomyoma involving the inferior vena cava and the tricuspid valve (n = 1),
      plexiform tumor of the sinoatrial node (n = 1), and papillary fibroelastoma of
      aortic valve noncoronary cusp (n = 1). There were no hospital deaths. Mean
      intensive care unit and hospital stays were 1.4 +/- 1.1 days and 7.3 +/- 3.4
      days, respectively. Postoperative complications were evolving stroke (n = 1), re
      exploration for bleeding (n = 1), and myocardial ischemia requiring stenting (n =
      1). Follow-up failed to demonstrate residual or recurrent tumor. One patient had
      a small residual atrial septal defect. Ninety-two percent of patients appreciated
      the cosmetic result and fast recovery. CONCLUSIONS: Endoscopic cardiac tumor
      resection is feasible and a valid oncologic approach with an attractive cosmetic
      advantage over median sternotomy.

PMID- 17532414
TI  - Incidence and risk factors of postoperative vocal cord paralysis in 987 patients
      after cardiovascular surgery.
AB  - BACKGROUND: Vocal cord paralysis (VCP) after cardiovascular surgery can affect
      the postoperative outcome. The aim of the present study was to clarify the
      incidence of VCP after cardiovascular surgery and the relationship between the
      surgery characteristics and the risk of VCP. METHODS: A total of 987 consecutive
      patients who underwent cardiovascular surgery (cardiac, n = 895; aortic, n = 92)
      were enrolled. We retrospectively assessed the incidence and the risk of VCP
      according to the length and types of surgery and the details of each VCP case and
      compared them between the aortic and the nonaortic group. RESULTS: Twenty-three
      patients (2.3%: cardiac, n =15; aortic, n = 8) were expertly diagnosed with VCP
      (left, n = 19; right, n = 2; bilateral, n = 2). In the multivariate analysis, the
      risk for VCP increased with the duration of the operation (odds ratio [OR], 4.4,
      95% confidence interval [CI] 1.7 to 11.4), and aortic procedures (OR, 5.6, CI 2.3
      to 13.5) exhibited higher risk compared with coronary artery bypass grafting.
      Among the VCP cases, the incidence of poor outcomes (ie, bilateral VCP, repeated
      airway treatment, death within 6 months) was significantly higher in the aortic
      group (p = 0.016). All patients that were intubated for longer than 100 hours
      exhibited poor outcomes. CONCLUSIONS: Aortic procedures and prolonged operation
      increase the risk of VCP. Severe VCP tended to be associated with aortic surgery
      and intubation for more than 100 hours.

PMID- 17532415
TI  - Selective endothelin-A receptor inhibition after cardiac surgery: a safety and
      feasibility study.
AB  - BACKGROUND: Increased synthesis and release of the bioactive peptide endothelin
      has been shown to change hemodynamics and postoperative recovery after cardiac
      surgery. However, the clinical effects of selective interruption of endothelin
      signaling have not been studied. Because the endothelin-A (ET-A) receptor subtype
      is the primary cardiovascular effector for endothelin, this study used the ET-A
      receptor antagonist sitaxsentan sodium (TBC11251Na) to evaluate: (1) dose
      dependent changes in pulmonary artery pressure (PAP) and pulmonary (PVRI) and
      systemic (SVRI) vascular resistance index in patients undergoing on-pump coronary
      revascularization; and (2) whether ET-RA administration was associated with
      increased adverse events. METHODS: Patients (n = 44, age, 62 +/- 1 years) were
      randomized to receive vehicle (n = 9) or different bolus infusions of ET-A
      receptor antagonist: 0.1 (n = 9), 0.5 (n = 9) 1.0 (n = 9), and 2.0 mg/kg (n = 8)
      at separation from cardiopulmonary bypass (CPB). Adverse events were tabulated
      until hospital discharge. Results were expressed as changes from a composite
      baseline value, or from time 0 due to a high degree of intrapatient measurement
      variability in the postoperative period. RESULTS: PAP increased by 27% +/- 13%
      from baseline (19 +/- 1 mm Hg) in the vehicle group at 6 hours post-CPB (p <
      0.05). PAP fell from this post-CPB vehicle value in a dose-dependent manner with
      the ET-A receptor antagonist; with a significant reduction observed at 2 mg/kg
      (7% +/- 8% increase from baseline, p < 0.05). PVRI was reduced by 28.6% +/- 16%
      from baseline (249 +/- 22 dyn x s x cm(-5) x m(-2)) in the 2 mg/kg ET-A receptor
      antagonist group at 30 minutes post-CPB and remained reduced up to 6 hours post
      CPB (p < 0.05). SVRI was reduced from baseline (2770 +/- 106 dyn x s x cm(-5) x
      m(-2)) by 51% +/- 6% in the 2.0 mg/kg ET-A receptor antagonist group at 30
      minutes post-CPB (p < 0.05) and remained reduced up to 6 hours post-CPB. A total
      of 203 adverse events were tabulated in the postoperative period and were equally
      distributed across the five treatment groups, with no direct attributions to ET-A
      receptor antagonist treatment. CONCLUSIONS: This unique study demonstrates that
      heightened endothelin-A receptor activation contributes to hemodynamic changes in
      patients after CPB. Selective inhibition of the endothelin receptor system can be
      successfully and safely performed in patients undergoing cardiac surgery and
      thereby reveals a potential, and clinically relevant therapeutic target.

PMID- 17532416
TI  - Early clinical and hemodynamic outcomes after stented and stentless aortic valve
      replacement: results from a randomized controlled trial.
AB  - BACKGROUND: Stentless aortic bioprostheses were shown to be hemodynamically
      superior to earlier generations of stented bioprostheses. Modern stented valve
      designs have improved hemodynamics. A prospective randomized controlled trial was
      undertaken to compare stentless versus modern stented valves. Our aim was to
      determine any differences in early postoperative clinical and hemodynamic
      outcomes. METHODS: Patients with severe aortic valve stenosis (n = 161)
      undergoing aortic valve replacement were randomized intraoperatively to receive
      either the C-E Perimount (Edwards Lifesciences, Irvine, CA) pericardial stented
      bioprosthesis (n = 81) or the Prima Plus (Edwards Lifesciences) (porcine
      stentless bioprosthesis (n = 80). Transthoracic echocardiograms were performed at
      one week and eight weeks postoperatively to assess left ventricular mass (LVM)
      and transvalvular gradients (TVG). RESULTS: There were no differences between the
      two groups in baseline characteristics. Cardiopulmonary bypass and ischemic times
      were longer in the stentless group. Despite similar native aortic annular
      diameters, the mean size of the prosthesis used in the stentless group was 2.1 mm
      (SD = 2.8) larger (p < 0.001). Early (30-day) mortality (stentless 3.7% vs
      stented 2.5%; p = 0.68) and morbidity was similar between groups. Eight weeks
      postoperatively, LVM (stentless 199 +/- 70 vs stented 204 +/- 66 grams; p = 0.32)
      and TVG decreased in both groups (mean systolic gradient; stentless 10 +/- 3 vs
      stented 10 +/- 4 mm Hg; p = 0.54) but there was no significant difference between
      groups. CONCLUSIONS: Despite longer ischemic times in the stentless group, early
      postoperative outcomes were similar. Both stented and stentless aortic valve
      replacement offers excellent hemodynamics and can be achieved with low
      perioperative mortality.

PMID- 17532417
TI  - Long-term results after the Rastelli repair for transposition of the great
      arteries.
AB  - BACKGROUND: This study sought to assess risk factors for late mortality after the
      Rastelli operation for patients with transposition of the great arteries,
      ventricular septal defect, and left ventricular outflow tract obstruction.
      METHODS: Records of 39 patients who underwent the Rastelli operation between 1977
      and 2004 were reviewed. Median age at the time of operation was 5.1 years (2.2
      years within the last 5 years). RESULTS: There were no early deaths. During a
      median follow-up of 8.9 years (range, 0 to 25 years), 2 patients died of sudden
      death, 1 of pneumonia, 1 during reoperation, and 2 received heart
      transplantation. Freedom from death or transplantation was 93.8% +/- 4.3% and
      57.5% +/- 15.1% at 10 and 20 years, respectively. Freedom from conduit
      replacement was 48.8% +/- 10.3% and 32.5% +/- 10.3% at 10 and 20 years,
      respectively. Subvalvular and valvular left ventricular outflow tract obstruction
      (p = 0.012), stenosis of the peripheral pulmonary arteries (p < 0.001),
      enlargement of the ventricular septal defect (p = 0.030), and longer ischemic
      time (p = 0.015) were predictive for death or transplantation. Patients younger
      than 4 years at the time of the Rastelli operation showed a trend toward a better
      freedom from death or transplantation (p = 0.068), but needed significantly more
      conduit replacements (p = 0.038) compared with patients 4 years or older.
      CONCLUSIONS: The Rastelli operation is a low-risk procedure with regard to early
      mortality. The status of the pulmonary arteries and ventricular septal defect
      enlargement are predictive for long-term survival. Patients 4 years of age or
      older at the time of the Rastelli operation require fewer reoperations for
      conduit exchange. Nevertheless, early Rastelli repair is recommended because
      patients 4 years or older are at risk for a higher long-term mortality.

PMID- 17532418
TI  - Unidirectional monovalve homologous aortic patch for repair of ventricular septal
      defect with pulmonary hypertension.
AB  - BACKGROUND: Severe pulmonary hypertension is a common complication of congenital
      cardiac defects with large left to right shunt, and the closure of a large
      ventricular septal defect (VSD) with elevated pulmonary vascular resistance (PVR)
      is associated with significant morbidity and mortality. A unidirectional
      monovalve homologous aortic patch was designed to close the large VSD with severe
      pulmonary hypertension in an effort to decrease the morbidity and mortality.
      METHODS: Twenty-seven patients (mean age, 15.0 +/- 5.6 years) with large VSD with
      severe pulmonary hypertension (pulmonary vascular resistance, 15.2 +/- 3.8 Wood
      units) were repaired with a unidirectional monovalve homologous aortic patch.
      According to body surface area and the preoperative arterial oxygen saturation,
      the monovalve homologous aortic patches were fenestrated on the aortic wall with
      a diameter of 4 to 8 mm. RESULTS: Two patients died of pulmonary hypertensive
      crisis and cardiac arrest postoperatively. All of the survival patients were
      followed up (5 months to 10 years) and the cardiopulmonary function was well
      improved with no late death. Obvious opening and closing of the monovalve was
      detected by early postoperative echocardiography in seven patients. A small
      amount of right to left shunt was detected in three patients three months after
      operation, and in two of them the shunt still existed three years after
      operation. CONCLUSIONS: Closure of a large VSD in patients with severe pulmonary
      hypertension could be performed with low morbidity and mortality when a
      unidirectional monovalve homologous aortic patch was used and the long-term
      result was satisfactory.

PMID- 17532419
TI  - Invited commentary.

PMID- 17532420
TI  - Introduction of a new optimized total cavopulmonary connection.
AB  - BACKGROUND: Several variations of the total cavopulmonary connection (TCPC) have
      been investigated for favorable fluid mechanics and flow distribution. This study
      presents a hemodynamically optimized TCPC configuration code-named "OptiFlo."
      Featuring bifurcated vena cava (superior venacava to inferior vena cava SVC/IVC),
      it was designed to lower the fluid mechanical power losses in the connection and
      to ensure proper hepatic blood perfusion to both lungs. METHODS: A rapid
      prototype model of the OptiFlo TCPC was built and in vitro control volume flow
      analysis was performed to evaluate the fluid mechanical power loss performance of
      the model. Furthermore, computational fluid dynamics simulations were used to
      investigate the flow patterns in the model, which were compared with those in the
      planar one-diameter offset TCPC with flared anastomosis sites, the best known
      TCPC configuration to date. RESULTS: Compared with the one-diameter offset
      reference model, the OptiFlo showed lower power losses: -26%, -31%, and -42% for
      increasing cardiac outputs of 2, 4, and 6 L/minute, respectively. No
      statistically significant differences were found in power loss between 40:60 and
      50:50 SVC/IVC flow ratios (p > 0.1) for the OptiFlo model. The power loss
      characteristic curve for different left and right pulmonary artery ratios was
      flatter for the OptiFlo than the one-diameter offset reference model. Pulmonary
      artery flow was much more streamlined in the OptiFlo compared with the one
      diameter offset model. CONCLUSIONS: The OptiFlo TCPC design exhibits lower power
      losses with better adaptive distribution of hepatic blood to both lungs and lower
      blood flow disturbances compared with the planar one-diameter offset TCPC model.
      Its significantly superior hemodynamic performance at higher cardiac outputs
      (exercise) rationalizes further design and feasibility studies toward a workable
      clinical model.

PMID- 17532421
TI  - Invited commentary.

PMID- 17532422
TI  - First human transplantation of a nonacceptable donor lung after reconditioning ex
      vivo.
AB  - PURPOSE: This article describes an ex vivo method to recondition and transplant
      rejected donor lungs. DESCRIPTION: A 19-year-old man was brain dead after a
      traffic accident. A roentgenogram showed bilateral lung contusion. He had ongoing
      intratracheal bleeding. After optimizing ventilator treatment and suctioning the
      airways, PaO2 was 9 kPa (67.5 mm Hg) on FiO2 = 0.7. The lungs were rejected by
      all transplantation centers in the Nordic countries. We harvested the lungs for
      research. The right lung was severely injured. The left lung was edematous with
      bleeding spots in the lower lobe, and the mediobasal segment was atelectatic. The
      left lung was reconditioned ex vivo and kept in topical extracorporeal membrane
      oxygenation until it was transplanted into a 70-year-old man with chronic
      obstructive pulmonary disease 17 hours later. EVALUATION: The transplanted lung
      functioned very well, and the patient recovered uneventfully. At 3 months
      control, a computed tomographic thoracic scan and transbronchial biopsies showed
      a normal left lung, and the patient was in very good clinical condition, only to
      succumb to death from unrelated events 11 months after the transplantation.
      CONCLUSIONS: Rejected donor lungs may be successfully transplanted after being
      reconditioned ex vivo.

PMID- 17532423
TI  - Invited commentary.

PMID- 17532424
TI  - Full-thickness chest wall resection for recurrent breast phyllodes tumor.
AB  - Phyllodes tumor is a rare breast neoplasm. We present the case of a woman who
      underwent multiple surgical procedures for phyllodes tumor treatment. Even after
      bilateral mastectomy and radiotherapy, local recurrences developed. We performed
      a full-thickness chest wall resection with wide margins, a procedure rarely
      reported in medical literature for this purpose. Only after this approach did we
      obtain disease control, with no signs of further recurrence at 4 years' follow
      up.

PMID- 17532425
TI  - Nodular lymphoid hyperplasia of the lung: a very rare disease entity.
AB  - Nodular lymphoid hyperplasia of the lung is an uncommon disease that is
      considered to be a benign lesion of a polyclonal lymphoid proliferation. Because
      of its rarity, little is known about the clinicopathologic characteristics of
      nodular lymphoid hyperplasia. Some researchers have questioned whether nodular
      lymphoid hyperplasias are truly reactive or are marginal zone B-cell lymphomas
      (low-grade lymphomas of mucosa-associated lymphoid tissue) mimicking reactive
      lymphoid processes. We present the case of a 67-year-old woman with nodular
      lymphoid hyperplasia of the lung and discuss the current knowledge concerning
      nodular lymphoid hyperplasias.

PMID- 17532426
TI  - Effective approach for the treatment of bronchopleural fistula: application of
      endovascular metallic ring-shaped coil in combination with fibrin glue.
AB  - The development of bronchopleural fistula is an important complication after
      pulmonary resections. Generally, conventional treatment methods are used in
      patients having bronchopleural fistulas. Recently, there has been an increase in
      the use of minimally invasive methods yielding better results. In our study, we
      applied a combination of endovascular metallic ring coil and fibrin glue. We
      hereby think that such an approach for a combination might be a contribution to
      improving the already existing minimally invasive treatment methods.

PMID- 17532427
TI  - Surgical management of a giant thoracic angiomyolipoma.
AB  - This report describes the surgical management of a tumor that filled the left
      chest of a 58-year-old man. Histopathologic examination showed that this was an
      angiomyolipoma, a tumor that most commonly occurs in the kidney. The preoperative
      evaluation and intraoperative management are presented, along with a brief review
      of this unusual neoplasm.

PMID- 17532428
TI  - Lipoma of the diaphragm: a rare presentation.
AB  - Lipoma of the diaphragm is an extremely rare entity. A 67-year-old asymptomatic
      man who had a tumor located in the posterior region of the left hemi-diaphragm is
      presented. The tumor was removed through a left mini-thoracotomy. The diaphragm
      was reconstructed primarily by using nonabsorbable suture material. The final
      pathologic examination revealed a mature lipoma. The patient remains without
      evidence of recurrence 60 months after the operation.

PMID- 17532429
TI  - Endoscopic correction of the adult form of scimitar syndrome and mitral
      regurgitation: anatomic and technical considerations.
AB  - Scimitar syndrome is a congenital cardiac anomaly characterized by anomalous
      venous drainage of the right lung into the inferior vena cava. We report the
      combination of scimitar syndrome and mitral regurgitation and describe port
      access correction for the adult form by means of an intraatrial baffle combined
      with mitral valve repair. Related considerations and modifications required in
      the standard Heartport (Cardiovations, Somerville, NJ) technique are discussed.

PMID- 17532430
TI  - Atrial septal rupture, flail tricuspid valve, and complete heart block due to
      nonpenetrating chest trauma.
AB  - This is a report of a patient with an atrial septal defect with right-to-left
      shunting, flail tricuspid valve, and complete heart block secondary to blunt
      chest trauma after a motor vehicle accident. The patient surgically repaired with
      pericardial recreation of atrial septum, bioprosthetic tricuspid valve
      replacement, and pacemaker insertion. The patient had minimal problems during the
      hospital course and subsequently made a full postsurgical recovery.

PMID- 17532431
TI  - Late disruption of a Freestyle stentless bioprosthesis used for repair of sinus
      of Valsalva aneurysm of noncoronary cusp.
AB  - We present a case of disruption of the porcine aortic wall of the 27-mm Freestyle
      stentless bioprosthesis 5 years after the subcoronary implantation to exclude the
      sinus of Valsalva aneurysm of the noncoronary cusp. At the urgent reoperation,
      the inflow suture line was found to be intact, and therefore a new stented valve
      was sutured with the inflow Dacron cuff after removal of ruptured valve. The
      subcoronary implantation technique creates a cavity between the prosthetic and
      native aortic walls filled with hematoma. The outflow suture line dehiscence
      caused blood flow into the cavity, porcine aortic wall rupture, and leaflet
      destruction.

PMID- 17532432
TI  - Extracorporeal membrane oxygenation for Swan-Ganz induced intraoperative
      hemorrhage.
AB  - We herein present the case of a 75-year-old woman undergoing double valve
      replacement who experienced a massive bronchial hemorrhage due to a Swan-Ganz
      catheter pulmonary artery perforation after weaning from cardiopulmonary bypass.
      Early institution of extracorporeal membrane oxygenation allowed treatment of
      severe hypoxemia, refractory to mechanical ventilation, and the discontinuation
      of hemoptysis. Once clinical stability was achieved, the patient underwent
      pulmonary artery angiography with successful pseudoaneurysm embolization. It is
      hoped that this information can provide further insight into the management of
      such a complication.

PMID- 17532433
TI  - Intraoperative veno-arterial hemofiltration during miniaturized extracorporeal
      bypass.
AB  - We report the case of a 71-year-old man with creatinine clearance of 41 mL/min
      and acute anterior ST-segment elevation who underwent urgent coronary artery
      bypass grafting. A continuous intraoperative veno-arterial hemofiltration with
      high volumes of exchange (35 mL/kg/h) was used in a series for a miniaturized
      extracorporeal bypass system to minimize the inflammatory response and to protect
      the kidneys of this patient who had preoperative renal dysfunction. The patient
      had an uneventful postoperative recovery.

PMID- 17532434
TI  - Thoracoabdominal aortic aneurysm associated with abdominal aortic and visceral
      arterial occlusion in a hemodialysis patient.
AB  - We report an extremely rare case of saccular thoracoabdominal aortic aneurysm
      associated with high abdominal aortic occlusion including the superior mesenteric
      and bilateral renal arteries in a patient requiring hemodialysis. Successful
      repair of the aneurysm and concomitant revascularization of the lower extremities
      was achieved using femoro-femoral bypass for perfusion of the lower body along
      with the visceral and intercostal arteries.

PMID- 17532435
TI  - Spontaneous restoration of patency in the free gastroepiploic artery graft: the
      living transplanted vascular system for coronary revascularization.
AB  - We report an incidence of coronary revascularization with the gastroepiploic
      artery in which angiography demonstrated patency at 1 month, severe narrowing at
      1 year, and restoration of patency associated with progression of proximal
      coronary disease at 8 years. This report documents the reversibility of the free
      gastroepiploic artery.

PMID- 17532436
TI  - Aortic valve lipoma.
AB  - Cardiac lipoma (especially on the aortic valve) is extremely rare. We report a
      patient suffering from shortness of breath, chest pain, and recent presyncopal
      episodes who was found to have a mass on the aortic valve with mild aortic
      regurgitation. The patient had an uneventful aortic valve replacement.

PMID- 17532437
TI  - Localized pericardial constriction resulting in a "dumbbell" heart.
AB  - We describe an unusual case of a young man presenting with calcific constrictive
      pericarditis. The patient had a history of restrictive cardiomyopathy and
      pericardial effusion during infancy and received antituberculous treatment.
      Investigations revealed the presence of thickened pericardium and a thickened
      calcific constrictive band around the atrioventricular groove posteriorly and
      over the infundibulum anteriorly. Intraoperatively, the band caused the heart to
      have a "dumbbell" appearance. A pericardiectomy was performed along with excision
      of the constricting band. The patient had an uneventful recovery.

PMID- 17532438
TI  - Valve-sparing operation for aortic root aneurysm late after Mustard procedure.
AB  - The aortic valve reimplantation technique leads to excellent clinical outcome in
      patients with aortic valve incompetence and aneurysms of the ascending aorta.
      This technique is now applied for aneurysms of ascending aorta, aortic dissection
      type A, and even dilatation of pulmonary autograft after the Ross operation. We
      report a case of aortic root dilatation late after a Mustard operation for
      transposition of the great arteries that was successfully managed by valve
      sparing aortic root reimplantation.

PMID- 17532439
TI  - Rare presentation of subclavian artery isolation in a neonate with a family
      history of aortic arch anomalies.
AB  - Isolation of the left subclavian artery is a rare aortic arch anomaly in which
      the artery originates from the pulmonary artery through a ductus arteriosus
      rather than the aorta. In neonates it is usually diagnosed incidentally with
      other aortic or cardiac anomalies and can be associated with chromosomal
      deletions. We describe an extremely rare presentation whereby subclavian artery
      isolation was presented with left arm ischemia in a 6-day-old child. There were
      also a concurrent right aortic arch, ventricular septal defect, persistent left
      superior vena cava, and both radial and ulnar artery hypoplasia. A family history
      of aortic arch anomalies with no known chromosomal aberration was also present,
      whereby all the male family members on the maternal side had undergone aorto
      cardiac surgery as neonates. Diagnosis and surgical management are discussed.

PMID- 17532440
TI  - Patent ductus arteriosus ligation: the LigaSure system may be unreliable.
AB  - Surgical ligation of a patent ductus arteriosus (PDA) in small premature infants
      may be performed with open thoracotomy or video-assisted thoracoscopic surgery
      (VATS). The LigaSure vessel sealing system (Valleylab/Tyco Healthcare, Boulder,
      CO) is increasingly being used because of its effectiveness in promoting
      coagulation. Moreover, for PDA ligation using VATS, the LigaSure system seems
      more practical than vascular clips. Among 81 children, including 43 premature
      infants weighing less than 1000 grams operated on for PDA in our institution, one
      9-month-old boy weighing 7600 grams underwent PDA ligation using a LigaSure
      grasp. The perioperative aspect of the closed ductus was satisfactory. The
      following day, however, ultrasound control revealed recanalization of the ductus,
      and the child had to undergo a second operation. At operation, the ductus wall
      adventia and media appeared to have retracted to both extremities, leaving the
      intima exposed and pulsating under the blood pressure. The PDA ligation was
      repeated, but in conditions of severe hemorrhage. The LigaSure system works by
      fusing collagen in the tissue. However, because the ductus wall has less collagen
      than any other vessels in the body, the LigaSure vessel sealing system is not
      reliable for PDA ligation.

PMID- 17532441
TI  - Migration and colon perforation of intraperitoneal cardiac pacemaker systems.
AB  - Epicardial pacemaker systems include pacing leads and a generator, which
      exceptionally may have to be implanted in the abdomen. We report three such
      pediatric cases where severe intraabdominal complications occurred owing to
      migration and erosion of the generators into visceral organs and urge extreme
      caution with this technique.

PMID- 17532442
TI  - Delayed pseudoaneurysm of the mitral-aortic intervalvular fibrosa.

PMID- 17532443
TI  - Mitral valve regurgitation due to a lipoma.

PMID- 17532444
TI  - Laparoscopic cardioplasty to avoid esophageal resection in patient not responsive
      to Heller myotomy.
AB  - Some achalasia patients do not ameliorate dysphagia after Heller myotomy. If
      stenosis does not respond to endoscopic dilatations and persists after a second
      extended myotomy, an esophageal resection is considered unavoidable. This article
      describes an original technique of treating this type of persistent stenosis with
      an esophageal stricturoplasty. The procedure was completed under laparoscopy. The
      postoperative course was uneventful. Resolution of all preoperative symptoms was
      achieved at the first year follow-up. Control of gastroesophageal reflux was
      documented by 24-hour pH-impedance. If confirmed by further cases, laparoscopic
      esophageal stricturoplasty could become a valid option for a conservative
      treatment of these patients.

PMID- 17532445
TI  - Video-mediastinoscope: for extracting upper esophageal foreign bodies.
AB  - Patients with esophageal foreign bodies require prompt diagnosis and therapy. The
      proximal dilatation method using a video-mediastinoscope is safe and effective in
      removing sharp foreign bodies from the upper esophagus, avoiding surgery and
      possible perforation. The technique using a video-mediastinoscope proved to be
      effective and safe; this may be the first use of this procedure in the
      literature. We recommend using video-mediastinoscope for extracting foreign
      bodies involving the upper esophagus narrowing.

PMID- 17532446
TI  - Valve-sparing reconstruction within the native aortic root: integrating the
      Yacoub and the David methods.
AB  - I propose an integrated valve-sparing aortic root reconstruction that combines
      the surgical principles of both the Yacoub and David methods. Valve re-suspension
      is first completed within the native aortic root; then the graft is anchored to
      the pledget-reinforced, scalloped true aortic annulus.

PMID- 17532447
TI  - Treatment of lone atrial fibrillation with a right thoracoscopic approach.
AB  - A simplified technique to treat patients in stand-alone atrial fibrillation with
      a right thoracoscopic approach is described. An electrical isolation of the four
      pulmonary veins (box lesion) is achieved with a microwave antenna.

PMID- 17532448
TI  - New method for sternal closure after vacuum-assisted therapy in deep sternal
      infections after cardiac surgery.
AB  - The treatment of nonhealing and infected sternotomies after cardiac surgery is a
      challenging task with increased rates of mortality and morbidity, as well as high
      costs. A local vacuum therapy (ie, the vacuum-assisted closure system) permits
      the treatment of deep sternal infections due to continuous aspiration and a
      sealed dressing that stimulates granulation tissue formation. Aggressive vacuum
      assisted closure treatment of the sternum in postoperative deep wound infection
      enhances sternal preservation and the speed of potential rewiring. After some
      weeks of vacuum-assisted closure therapy, a complete preparation of the
      substernal structures is necessary. In this context, laceration of the right
      ventricle is a rare but life-threatening complication. We describe a new
      technique for sternal closure after vacuum-assisted wound treatment using Nitinol
      clips (Praesidia, Bologna, Italy), which can prevent these severe complications.
      Without any preparation of the substernal tissue the clips can be inserted in the
      parasternal space with consecutive proper stabilization of the sternum. This new
      method represents an easy, low-cost and complication-free procedure.

PMID- 17532449
TI  - Modified simple sliding aortoplasty for supravalvar aortic stenosis.
AB  - We describe a modified simple sliding aortoplasty for supravalvar aortic
      stenosis. This technique is easier, has a more physiologic approach, and has the
      advantage of not using foreign material to provide aortic growth potential in
      children. For the patients presented in this study, the mid-term results of
      modified simple sliding aortoplasty have showed good results.

PMID- 17532450
TI  - Intraoperative imaging techniques to assess coronary artery bypass graft patency.
AB  - Graft patency verification is increasingly recognized as an important component
      of coronary artery bypass grafting. Intuitively, eliminating intraoperative graft
      failure should reduce cardiac mortality and morbidity in the short term and
      improve clinical outcome in the long term. Although conventional angiography
      remains the gold standard technique for assessing graft patency, it is rarely
      available in the operating room and consequently several other less invasive
      approaches have been advocated. This article reviews the two currently most
      commonly used modalities for graft patency assessment, intraoperative
      fluorescence imaging and transit-time flowmetry, and discusses their value and
      limitations. Both techniques can reliably detect otherwise unsuspected occluded
      grafts and this is crucial for internal thoracic arteries because of their
      prognostic significance. Although neither technology can consistently identify
      more minor, non-occlusive abnormalities, the intraoperative fluorescence imaging
      technique seems to be more sensitive and less susceptible to "false positive"
      images.

PMID- 17532451
TI  - Pulmonary complications after lung resection are increased in patients with
      previous head and neck cancer.

PMID- 17532452
TI  - Use of flexible silastic drains in thoracic surgery: a word of caution.

PMID- 17532453
TI  - Use of pedicled omentum and endostaplers in esophagogastric anastomosis.

PMID- 17532456
TI  - Blood transfusion after cardiac surgery: damned if you don't. damned if you do?

PMID- 17532457
TI  - Edge-to-edge mitral valve repair: a "safe and useful" technique?

PMID- 17532458
TI  - Ductal origin of the distal pulmonary artery in truncus arteriosus.

PMID- 17532460
TI  - Cryopreservation of goat spermatozoa: comparison of two freezing extenders based
      on post-thaw sperm quality and fertility rates after artificial insemination.
AB  - TRIS-glucose or skim milk extenders are most commonly used for cryopreserving
      goat sperm. The aim of this study was to compare the ability of two extenders
      based on TRIS and skimmed milk buffer to maintain sperm viability after
      cryopreservation. Goat semen samples (n=110) were frozen with TRIS and with milk
      extender and thaw. Sperm motion parameters, morphology and acrosomal integrity
      were assessed in fresh and frozen-thawed samples by Sperm Class Analyzer (SCA)
      and Diff-Quik and Spermac staining techniques. Pregnancy rates were obtained
      after cervical insemination with frozen semen doses. The cryopreservation process
      had a significant effect on acrosome and kinematic parameters. TRIS extender
      provided more effective preservation of total motility, velocity parameters and
      amplitude of lateral head displacement after freezing. The percentage of acrosome
      intact spermatozoa was significantly higher in samples diluted with milk
      extender. In the insemination doses, mean values of velocity parameters and
      lateral head displacement were higher in doses processed in TRIS. Spermatozoa
      frozen in milk extender was mathematically greater than for those frozen with
      TRIS extenders, though no significant difference exists. We conclude that post
      thaw kinematic parameters and acrosome integrity assessed after 1h of incubation
      was acceptable in both extenders which indicated the feasibility of
      cryopreserving goat spermatozoa. TRIS extender results in better in vitro
      performance compared to milk, though these improvements were not reflected in
      fertility results. Semen doses cryopreserved in milk extender provided greater
      pregnancy rates after intra-cervical insemination compared to those in TRIS
      extender (52.4% versus 42.9%).

PMID- 17532461
TI  - Serum markers for predicting pre-eclampsia.
AB  - Pre-eclampsia, a pregnancy-specific disorder, contributes substantially to
      perinatal morbidity and mortality of both, mother and newborn. An increasing
      number of biochemical agents were evaluated as markers for predicting pre
      eclampsia. None of them has been proved to be of clinical value yet. Much effort
      has been put into assessing novel potential markers and their combination with
      other screening methods such as Doppler sonography. The purpose of this review is
      to reflect the current knowledge of serum markers for predicting pre-eclampsia.
      So far, the most promising serum markers are placental protein 13 (PP-13), as
      well as soluble fms-like tyrosine kinase-1 (sFlt-1), placental growth factor
      (PIGF) and soluble endoglin (sEng). These markers allow screening at a relatively
      early stage and, most importantly, show relatively high predictive values and
      improved diagnostic performance if combined with first trimester Doppler
      sonography. Large-scale prospective studies, assessing these markers, are
      important to justify their clinical use in view of early intervention to prevent
      pre-eclampsia in the future.

PMID- 17532462
TI  - 11beta-Hydroxysteroid dehydrogenase type 2 in pregnancy and preeclampsia.
AB  - Cortisol availability is controlled by 11beta-hydroxysteroid dehydrogenase type 2
      (11beta-HSD2), which inactivates cortisol in cortisone, unable to bind to the
      glucocorticoid receptor. The 11beta-HSD2 enzyme activity limits either
      intracellular cortisol concentrations or within the uteroplacental compartment
      the transfer of cortisol into the fetal circulation. Mechanisms, by which 11beta
      HSD2 activity is controlled, include transcriptional control, posttranscriptional
      modifications of 11beta-HSD2 transcript half-life, epigenetic regulation via
      methylation of genomic DNA and direct inhibition of enzymatic activity. The
      11beta-HSD2 expression and activity is reduced in preeclampsia and the enzyme
      activity correlates with factors associated with increased vasoconstriction, such
      as an increased angiotensin II receptor subtype 1 expression, and notably fetal
      growth. Numerous signals such as proinflammatory cytokines known to be present
      and/or elevated in preeclampsia regulate 11beta-HSD2 activity. Shallow
      trophoblast invasion with the resulting hypoxemia seems to critically reduce
      available 11beta-HSD2 activity. A positive feedback exists as activated
      glucocorticoid receptors do enhance 11beta-HSD2 mRNA transcription and mRNA
      stability. No data are currently available on pregnancy and either epigenetic or
      direct effects on the activity of the translated enzyme.

PMID- 17532463
TI  - Inflammatory response in preeclampsia.
AB  - The origin of preeclampsia, a disease unique to pregnancy is still matter of
      debate and numerous theories have been proposed. The pathophysiology of the
      disease involves impaired trophoblast invasion, abnormal genetic polymorphism,
      vascular endothelial cell activation, immune intolerance by the maternal immune
      system, but also an exaggeration of a systemic inflammatory process. Preeclampsia
      is one of the major causes of maternal and perinatal morbidities including
      preterm births and therefore merits ongoing intensive research. The inflammatory
      process is determined by immunogenetic and non-immunogenetic factors. While
      inflammation mostly appears to be related to immunogenic determinants such as HLA
      antigens, paternity, monocytes, proinflammatory cytokines and NK cells, also
      responses not directly related to the immune system have been observed such as
      related to hypoxia or agonistic autoantibodies directed against vasoconstrictive
      angiotensin II receptors. The HIF-modulated reactions open up a new field in
      research as recently published data show the complexity of these factors.

PMID- 17532464
TI  - A novel canine lymphoma cell line: a translational and comparative model for
      lymphoma research.
AB  - A novel canine lymphoma cell line, OSW, was established from the malignant
      pleural effusion of a dog with peripheral T-cell lymphoma. The immunoprofile as
      determined by flow cytometry was as follows: positive for CD45, CD49d, CD18,
      CD11a; weakly positive for CD11b, CD11c, CD11d; and negative for CD45RA, CD1a,
      CD1c, CD3, TCRalphabeta, TCRgammadelta, CD4, CD5, CD8a, CD8b, CD90(Thy1), CD21,
      MHCII, CD14(TUK4), CD34, and MPO. Immunocytochemistry of cytospin preparations
      was negative for cytoplasmic CD3, CD79a, and MPO, but was positive for CD20. The
      cell line had an oligoclonal T-cell receptor gamma (TCRgamma) gene rearrangement.
      Array comparative genomic hybridization (aCGH) and single locus probe (SLP)
      analysis showed that there were copy number increases of loci on dog chromosome
      13 (CFA 13), and copy number decreases were evident for regions of CFA 11, 22,
      26, 30 and 32, which include several of the more common chromosomal aberrations
      reported previously in canine lymphoma. The OSW cell line grows rapidly in vitro
      and is tumorigenic as a xenograft in SCID/NOD mice. OSW represents one of only a
      few reported canine lymphoma cell lines and is the most thoroughly characterized.
      This cell line and xenograft represent significant in vitro and in vivo models,
      respectively, for comparative and translational lymphoma research.

PMID- 17532465
TI  - Long-term physical and mental health consequences of childhood physical abuse:
      results from a large population-based sample of men and women.
AB  - OBJECTIVE: Child maltreatment has been linked to negative adult health outcomes;
      however, much past research includes only clinical samples of women, focuses
      exclusively on sexual abuse and/or fails to control for family background and
      childhood characteristics, both potential confounders. Further research is needed
      to obtain accurate, generalizable estimates and to educate clinicians who are
      generally unaware of the link between childhood abuse and adult health. The
      purpose of this project is to examine how childhood physical abuse by parents
      impacts mid-life mental and physical health, and to explore the attenuating
      effect of family background and childhood adversities. METHODS: We analyzed
      population-based survey data from over 2,000 middle-aged men and women in the
      Wisconsin Longitudinal Study using self-reported measures of parental childhood
      physical abuse, mental health (depression, anxiety, anger), physical health
      (physical symptoms and medical diagnoses), family background, and childhood
      adversities. RESULTS: Parental physical abuse was reported by 11.4% of
      respondents (10.6% of males and 12.1% of females). In multivariate models
      controlling for age, sex, childhood adversities, and family background, we found
      that childhood physical abuse predicted a graded increase in depression, anxiety,
      anger, physical symptoms, and medical diagnoses. Childhood physical abuse also
      predicted severe ill health and an array of specific medical diagnoses and
      physical symptoms. Family background and childhood adversities attenuated but did
      not eliminate the childhood abuse/adult health relationship. CONCLUSIONS: In a
      population-based cohort of middle-aged men and women, childhood physical abuse
      predicted worse mental and physical health decades after the abuse. These effects
      were attenuated, but not eliminated, by age, sex, family background, and
      childhood adversities.

PMID- 17532466
TI  - Compartmentalisation of T cells expressing CD8alpha and TCRbeta in developing
      thymus of sea bass Dicentrarchus labrax (L.).
AB  - Eggs, larvae, post-larvae and sexually immature juveniles of the teleost
      Dicentrarchus labrax (L.) were assayed for the expression of genes encoding the T
      cell receptor beta and CD8alpha. RT-PCR of RNA extracted from larvae revealed
      TCRbeta transcripts from day 25 post-hatching (ph) and CD8alpha transcripts from
      26 days later. At day 51 ph, CD8alpha and TCRbeta mRNAs were localised by in situ
      hybridisation in thymocytes of the outer and lateral zones of the thymic paired
      glands. From day 75 ph onwards the signal was mainly detected in the outer
      region, drawing a cortex-medulla demarcation. In 1-year-old fish, CD8alpha+ and
      TCRbeta+ thymocytes almost filled the cortex and extended in large cords in the
      medulla. A CD8alpha(-)TCRbeta+ subcapsular lymphoid zone was evident near the
      septa coming from the inner connective capsule that delimited the thymus. The
      localisation of CD8alpha and TCRbeta transcripts demonstrated a
      compartmentalisation of the juvenile thymus due to distinct localisation of
      thymocytes at different developmental stages.

PMID- 17532467
TI  - Heavy metals in mosquito larval habitats in urban Kisumu and Malindi, Kenya, and
      their impact.
AB  - Concentrations and distribution of cadmium, chromium, copper, iron, lead,
      manganese and zinc in mosquito larval habitats in urban Kisumu and Malindi, Kenya
      and their effect on the presence of Anopheles gambiae, Aedes aegypti, Culex
      quinquefasciatus and Anopheles funestus larvae were investigated. Manganese and
      iron were the most prevalent heavy metals in water of larval habitats in urban
      Kisumu and Malindi, respectively. Iron was the most prevalent heavy metal in
      bottom sediments in larval habitats in both cities. The highest concentrations of
      all heavy metals, except cadmium and iron, were recorded in the poorly planned
      well drained stratum in the two cities. All heavy metals were more concentrated
      in human-made than in natural larval habitats. Copper was positively associated
      with the presence of Ae. aegypti, and lead was associated with the presence of
      An. gambiae and Ae. aegypti in urban Kisumu. Absence of significant correlation
      between the other metals and mosquito species in both cities, despite relatively
      high concentrations, suggest that the local larval populations, including key
      malaria vectors have adapted to the detected levels of these metals.

PMID- 17532468
TI  - Phytotoxicity of municipal sewage sludge composts related to physico-chemical
      properties, PAHs and heavy metals.
AB  - The aim of the study was to determine the influence of the composting on the
      phytotoxicity of sewage sludge in relation to their physical-chemical properties,
      heavy metals and polycyclic aromatic hydrocarbons content. Four municipal sewage
      sludges were composted for 76 days. A Phytotoxkit Test and pot experiment with
      Lepidium sativum were used for bioassay. The total PAH content in sludges ranged
      from 3674.1 to 11236.3 microg kg(-1). Heavy metals content was in the range Cd
      (1.9-76 mg kg(-1)), Cr (27.6-120 mg kg(-1)), Cu (156-335 mg kg(-1)), Pb (37.5
      59.5 mg kg(-1)), Ni (21.7-155 mg kg(-1)) and Zn (1015-1385 mg kg(-1)). The
      results showed a varied toxicity of sewage sludge in relation to the plant
      tested. In the case of two sludges a 100% inhibition of seed germination were
      noted. Sludge composting limited their negative influence on most of the
      phytotoxicity parameters. Only chlorophyll concentration was often lower than in
      the plant bred on compost obtained from sludge.

PMID- 17532469
TI  - Effects of subchronic digestive exposure to organic or inorganic cadmium on
      biomarkers in rat tissues.
AB  - In an experimental food chain, Wistar rats were fed cadmium (Cd) in an inorganic
      (CdCl(2)) or organic (mainly associated with metallothionein from Helix aspersa
      snail viscera) form. After 1 month of exposure to 100 microg inorganic Cd g(-1)
      in food, an induction of metallothionein was observed in all target tissues. In
      liver, glutathione peroxidase (GSH-Px) activity decreased and alanine
      aminotransferase (ALAT) activity increased, suggesting that Cd causes
      hepatotoxicity. However, lipid peroxidation as well as catalase and caspase 3 (a
      marker of apoptosis) activities were not modified. At a rather low exposure (2.5
      microg Cd g(-1)), metallothionein level in the kidney was found to be the most
      sensitive biomarker of exposure for both Cd forms. In the small intestine of rats
      ingesting inorganic Cd, metallothionein expression was significantly higher than
      that observed for rats fed organic Cd. Present results allowed proposing a simple
      design to assess the effect of a chemical in a trophic transfer approach.

PMID- 17532470
TI  - Protection of rainbow trout (Oncorhynchus mykiss) from lactococcosis by probiotic
      bacteria.
AB  - We analysed the effect of probiotic supplementation on the control of
      lactococcosis in rainbow trout. Probiotic strains Leuconostoc mesenteroides CLFP
      196 and Lactobacillus plantarum CLFP 238 were administered orally to fish for 30
      days at 10(7) CFU g(-1) feed. Thirty days after the start of the probiotic
      feeding, fish were challenged with Lactococcus garvieae. Probiotic
      supplementation reduced fish mortality significantly, from 78% in the control
      group to 46-54% in the probiotic groups.

PMID- 17532471
TI  - Event-related phase reorganization may explain evoked neural dynamics.
AB  - The traditional view holds that event-related potentials (ERPs) reflect fixed
      latency, fixed polarity evoked responses that appear superimposed on the
      'background EEG'. The validity of the evoked model has been questioned by studies
      arguing that ERPs are generated at least in part by a reset of ongoing
      oscillations. But a proof of phase reset that is distinct from the 'artificial'
      influence of evoked components on EEG phase-has been proven difficult for a
      variety of methodological reasons. We argue that a theoretical analysis of the
      assumptions and empirical evaluation of predictions of the evoked and oscillatory
      ERP model offer a promising way to shed new light on mechanisms generating ERPs
      that goes well beyond attempts to prove phase reset. Research on EEG oscillations
      documents that oscillations are task relevant and show a common operating
      principle, which is the control of the timing of neural activity. Both findings
      suggest that phase reorganization of task relevant oscillations is a theoretical
      necessity. We further argue and show evidence that (i) task relevant oscillations
      exhibit a typical interactive and task relevant relationship between pre- and
      poststimulus power in the theta and alpha frequency range in a way that small
      prestimulus power is related to large poststimulus power and vice versa, (ii) ERP
      (interpeak) latencies and (iii) ERP amplitudes reflect frequency characteristics
      of alpha and theta oscillations. We emphasize that central assumptions of the
      evoked model cannot be substantiated and conclude that the ERPR model offers a
      new way for an integrative interpretation of ongoing and event-related EEG
      phenomena.

PMID- 17532472
TI  - A novel therapeutic target in various lung diseases: airway proteases and
      protease-activated receptors.
AB  - Protease-activated receptors (PAR), which are G protein-coupled receptors, have 4
      members, PAR-1 to PAR-4. PARs are activated by proteolysis of a peptide bond at
      the N-terminal domain of the receptor. PARs are widely distributed throughout the
      airways. Their activity is modulated by airway proteases of endogenous and
      exogenous origin, which can either activate or disable the receptors. The
      regulation of PAR activity by proteases is important under pathological
      conditions when the activity of proteases is increased. Moreover, various
      inflammatory mediators, such as cytokines, growth factors, or prostanoids, alter
      the PAR expression level. Elevated PAR levels are observed in various lung
      disorders, and their significance in the development of pathological situations
      in the lung is currently intensively investigated. Consequences of PAR activation
      can be either beneficial or deleterious, depending on the PAR subtype. PAR-1 has
      been shown to be an important player in the development of pulmonary fibrosis.
      Thus, PAR-1 represents an exciting target for clinical intervention in fibrotic
      diseases. PAR-2 contributes to allergic airway inflammation. However, the
      question whether the impact of PAR-2 is beneficial or deleterious is still under
      intensive discussion. Therefore, precise information concerning the participation
      of PAR-2 in various lesions is required. Moreover, it is necessary to generate
      selective PAR- and organ-targeted approaches for treating the diseases. A
      thorough understanding of PAR-induced cellular events and the consequences of
      receptor blockade may help in the development of novel therapeutic strategies
      targeted to prevent lung destruction and to avoid deterioration of conditions of
      patients with inflammatory or fibrotic lung diseases.

PMID- 17532473
TI  - Axonal regeneration stimulated by erythropoietin: an experimental study in rats.
AB  - The aim of the present study is to evaluate the effects of erythropoietin to the
      collateral sprouting by using systemically delivered erythropoietin in an end-to
      side nerve repair model. Forty-five rats were evaluated in four groups: (A) end
      to-side neurorrhaphy only, (B) end-to-side neurorrhaphy and erythropoietin
      administration, (C) end-to-end neurorrhaphy and (D) nerve stumps buried into
      neighboring muscles. In all animals, the contralateral healthy side served as
      control. Functional assessment of nerve regeneration was performed at intervals
      up to 5 months using the Peroneal Function Index. Evaluation 150 days after
      surgery included peroneal and tibial nerve morphometric examination, and wet
      weights of the tibialis anterior muscle. During the first three weeks after
      surgery, when erythropoietin was regularly administered, functional evaluation
      showed that erythropoietin may facilitate peripheral nerve regeneration. However,
      there was rapid deterioration in the functional recovery when erythropoietin's
      administration was discontinued. As a consequence, at the end of this study,
      erythropoietin failed to maintain its initial stimulating effect in axonal
      regeneration. The results of wet muscle weights revealed statistically
      significant differences between Groups A and C, and Group B. Furthermore, data on
      axonal counting showed significant difference between Groups A and C, and Group
      B. Erythropoietin appears to facilitate peripheral nerve regeneration at the
      initial phase of its administration. Further investigation will be necessary to
      optimise the conditions (dose, mode of administration) in order to maintain its
      effects.

PMID- 17532474
TI  - The CatWalk gait analysis in assessment of both dynamic and static gait changes
      after adult rat sciatic nerve resection.
AB  - Functional repair of neurotmesis has been proven most challenging in regenerative
      medicine. Progress in this field has shown that functional repair not only
      requires axon regeneration, but also selectivity in target reinnervation.
      Although selectivity in target reinnervation still involves relatively unexplored
      avenues, evidence-based medicine, in the end, requires behavioral proof of
      repair. Therefore, there is a need for tests assessing behavioral deficits after
      neurotmesis. To date, behavioral tests for detecting both dynamic and static
      parameters are limited. The CatWalk gait analysis has been shown to detect a
      multitude of speed-controlled dynamic and static gait deficits after experimental
      spinal cord injury. Therefore, we here evaluated its use in detecting both
      dynamic and static gait deficits after neurotmesis. After rat sciatic nerve
      resection CatWalk testing was performed for 8 weeks. A large amount of dynamic
      and static gait parameters were detected to be immediately and severely affected
      in the ipsilateral paw, sometimes reaching levels of only 15% of those of the
      unaffected paw. We conclude that the CatWalk objectively detects dynamic and
      static gait impairments after sciatic nerve resection and future experiments are
      now required to prove which of these parameters are of particular interest to
      detect functional repair.

PMID- 17532475
TI  - Anatomic brain magnetic resonance imaging of the basal ganglia in pediatric
      bipolar disorder.
AB  - BACKGROUND: Basal ganglia (BG) enlargement has been found in studies of adults
      with bipolar disorder (BPD), while the few studies of BPD youths have had mixed
      findings. The BG (caudate, putamen, globus pallidus, nucleus accumbens) is
      interconnected with limbic and prefrontal cortical structures and therefore may
      be implicated in BPD. METHODS: Sixty-eight youths (46 with BPD, 22 healthy
      controls) received neurological and psychiatric assessment, semi-structured
      interviews, and neuropsychological testing, followed by anatomic magnetic
      resonance imaging on a 1.5 Tesla scanner. After image segmentation, log BG
      volumes and asymmetry indices were analyzed using MANOVAs controlling for the
      effects of cerebral volume, age, sex, and diagnosis. These omnibus tests were
      followed by univariate linear regression models of each BG structure. RESULTS:
      Youths with BPD had a trend for larger right nucleus accumbens (NA) volumes (p =
      0.089). There were no significant group asymmetry differences, nor volume
      differences in the caudate, putamen, and globus pallidus. When analyzed
      separately by pubertal status, the prepubertal group had significantly larger
      total NA (p = 0.035) versus healthy controls, while the pubertal group did not
      show significant differences in the NA versus healthy controls. LIMITATIONS: The
      size of the control group is relatively small, possibly limiting our power to
      detect significant group differences. The inter-rater reliability for the NA is
      not as strong as the other structures; the finding of volume differences in this
      structure is preliminary and warrants replication. CONCLUSIONS: Youths with BPD
      had larger right NA volumes; this enlargement was most pronounced in the
      prepubertal group. The differences between these findings and those seen in adult
      BPD imply a neurodevelopmental phenomenon.

PMID- 17532476
TI  - TLR2-mediated cell stimulation in bacterial vaginosis.
AB  - Bacterial vaginosis (BV) is associated with preterm labor, pelvic inflammatory
      disease (PID) and increased HIV acquisition, although the pathways that mediate
      these pathological effects have not been elucidated. To determine the presence of
      Toll-like receptor (TLR)-ligands and their specificity in BV, genital tract
      fluids were collected from women with and without BV by cervicovaginal lavage
      (CVL). The CVL samples were evaluated for their ability to stimulate secretion of
      proinflammatory cytokines and to activate NFkappaB and the HIV long terminal
      repeat (LTR), indicators of TLR activation, in human monocytic cells. Stimulation
      with BV CVLs induced higher levels of IL-8 and TNFalpha secretion, as well as
      higher levels of HIV LTR and NFkappaB activation, than CVLs from women with
      normal healthy bacterial flora. To identify which TLRs were important in BV, 293
      cells expressing specific TLRs were exposed to CVL samples. BV CVLs induced
      higher IL-8 secretion by cells expressing TLR2 than CVLs from women without BV.
      Surprisingly, BV CVLs did not stimulate cells expressing TLR4/MD2, although these
      cells responded to purified lipopolysaccharide (LPS), a TLR4 ligand. BV CVLs, in
      cells expressing TLR2, also activated the HIV LTR. Thus, these studies show that
      soluble factor(s) present in the lower genital tract of women with BV activate
      cells via TLR2, identifying a pathway through which BV may mediate adverse
      effects.

PMID- 17532477
TI  - Lipopolysaccharide stimulates Epac1-mediated Rap1/NF-kappaB pathway in Raw 264.7
      murine macrophages.
AB  - Nuclear factor-kappa B (NF-kappaB) is regulated by various stimulants to show
      many physiological results. Lipopolysaccharide (LPS) activates NF-kappaB through
      toll-like receptor 4 (TLR4)-dependent signal transduction. LPS-treatment also
      produces cyclic AMP (cAMP) in Raw 264.7 murine macrophages. Two principal
      effector proteins for cAMP are protein kinase A (PKA) and cAMP-responsive guanine
      nucleotide exchange factor (Epac), a Rap GDP exchange factor. Here, we
      investigated whether NF-kappaB can be activated by cAMP production through Epac1
      mediated Rap1 activation by using Epac-specific cAMP analogue, 8-(4-chloro
      phenylthio)-2'-O-methyladenosine-3',5'-cyclic monophosphate (CPT). NF-kappaB
      activity was increased by the treatment with CPT but it was reduced by co
      transfection with dominant negative of Rap1 (Rap1N17). In conclusion, NF-kappaB
      activation should be regulated through Epac1-mediated Rap1 stimulation for LPS
      induced inflammatory responses in murine macrophages. It suggests that Epac1
      mediated Rap1/NF-kappaB pathway could be helpful for interpretation on various
      cAMP-mediated physiological responses and it could be used as a target to control
      their pathological abnormalities.

PMID- 17532478
TI  - OSAS in Down syndrome: T&A versus T&A plus lateral pharyngoplasty.
AB  - OBJECTIVE: Obstructive Sleep Apnea Syndrome (OSAS) is common in children with
      Down syndrome (DS). Adenotonsillectomy (T&A) has traditionally been the initial
      surgical treatment. More aggressive surgery has also been recommended. Previous
      studies have used parental reporting and not objective data to assess treatment
      outcomes. Polysomnography (PSG) is used to objectively evaluate the results of
      T&A versus T&A plus lateral pharyngoplasty in the initial treatment of OSAS in
      children with DS. METHODS: This is a retrospective study of children with OSAS
      and DS. Group 1 consisted of 21 children with DS who underwent T&A. Group 2
      consisted of 16 children of similar age who had T&A plus lateral pharyngoplasty
      as initial surgical treatment. Post-operative PSG's were available for all
      patients. Apnea/hypopnea index (AHI), presence of hypoxemia and hypercarbia, and
      arousal index were measured and compared. RESULTS: In group 1, after T&A, 48%
      continued to have an elevated AHI. If hypercarbia and hypoxemia are included in
      the result analysis, 67% continued to have abnormal PSG's after their surgery. In
      group 2, 63% had an elevated AHI post-operatively. When hypercarbia and hypoxemia
      are included in the analysis, 75% continued to have abnormal PSG's after surgery.
      There was no statistically significant difference in the outcome of the two
      groups. CONCLUSIONS: Pediatric patients with OSAS and DS may show improvement
      after T&A, however only about one third will have a normal post-operative sleep
      study. Adding a lateral pharyngoplasty does not improve these results. Further
      study with objective outcome data is needed to determine a better first line
      surgical treatment for these patients.

PMID- 17532479
TI  - MB11 BERAphone and auditory brainstem response in newborns at audiologic risk:
      comparison of results.
AB  - OBJECTIVE: To compare the diagnostic effectiveness of Automated Auditory
      Brainstem Responses (MB11 technique) with that of standard Auditory Brainstem
      Responses (ABR) in a sample of newborns evaluated after the second month of life.
      METHODS: From October 2002 to February 2005, audiologic evaluations were
      performed in full-term newborns who presented altered otoacoustic emissions and
      in newborns considered at audiologic risk admitted to the ENT (Ear Nose Throat)
      Unit of Giannina Gaslini Institute, Genoa, Italy. Our sample included 201
      children (104 males and 97 females) who underwent on the same day an audiologic
      test using MB11 BERAphone Maico and standard ABR test. RESULTS: Out of the 388
      ears examined, 378 (97.4%) showed agreement between the two techniques, whereas
      in 10 (2.6%) there was no agreement. Interobserver agreement was excellent
      (kappa=0.92+/-0.02 S.E., p=0.0001). The MB11 test yielded no false negatives and
      10 false positives which resulted normal at ABR. The MB11 test showed very good
      specificity 96.8% (95% CI 94.8-98.7%) and sensitivity 100% (95% CI 93.9-100%),
      positive predictive value 88.2% (95% CI 79-93.9%) and negative predictive value
      100% (95% CI 98.4-100%) for diagnosis of hearing loss. CONCLUSIONS: The results
      obtained confirm the absolute validity of MB11 screening test in subjects at
      audiologic risk. Furthermore, the test can be used to esclude normal hearing
      subjects (threshold 40 dB HL) and to refer hearing loss subjects to subsequent
      ABR for diagnosis.

PMID- 17532480
TI  - Construction and characterization of monoclonal antibodies specific for the R
      transactivator 185 of Epstein-Barr virus.
AB  - Epstein-Barr virus (EBV) has been implicated in the pathogenesis of several human
      malignancies including B lymphomas and nasopharyngeal carcinoma. The EBV R
      transactivator (Rta) has been found to play essential roles in stimulating a
      lytic cycle and viral gene expression. Recently, it was shown that ELISA
      detecting serum IgG-Rta(150+185) (two internal fragments of Rta) levels may be
      useful as a serological parameter to assist in the diagnosis of nasopharyngeal
      carcinoma. The present studies were to prepare monoclonal antibodies specific for
      the Rta185 and provide a useful tool for the detection of Rta. For this purpose,
      two monoclonal antibodies (Mabs) specific for the Rta185 were generated. They
      were identified by Western blot, enzyme-linked immunosorbent assay (ELISA) and
      immunofluorescence analysis. The results revealed two different
      immunofluorescence patterns in EBV-positive B cells and epithelial cells, and
      suggested that there might be a difference in EBV replication mode between B
      cells and epithelial cells. The Mabs obtained in this study have a potential for
      the diagnosis of EBV associated diseases.

PMID- 17532481
TI  - High-level expression of recombinant dengue virus type 2 envelope domain III
      protein and induction of neutralizing antibodies in BALB/C mice.
AB  - Dengue fever is a growing public health problem in many countries since so far no
      effective vaccines are available. In this study, the domain III of dengue virus
      type 2 envelope was expressed in Escherichia coli without fusion of any carrier
      protein. The recombinant protein was detected in the form of inclusion bodies,
      which were solubilized in 8M urea and could be purified subsequently by high
      performance liquid chromatography (HPLC) on an ion exchange column. After
      refolding, the recombinant protein inhibited the DEN-2 plaque formation on C6/36
      cells, demonstrated its function of receptor-interaction was retained. The
      recombinant protein was inoculated into BALB/c mice to test its immunogenicity
      and ability to induce neutralizing antibodies. The mice immunized with the
      purified protein developed high antibody titers. A neutralizing titer of 1:64 was
      also obtained by a cytopathogenic effect (CPE) inhibition assay in C6/36 cells.
      Mice challenged with lethal dose of DEN-2 in combination with sera from immunized
      mice were protected completely. The results suggested that these expression and
      purification strategies have the potential for development of an inexpensive
      vaccine.

PMID- 17532482
TI  - Network and intrinsic cellular mechanisms underlying theta phase precession of
      hippocampal neurons.
AB  - Hippocampal 'place cells' systematically shift their phase of firing in relation
      to the theta rhythm as an animal traverses the 'place field'. These dynamics
      imply that the neural ensemble begins each theta cycle at a point in its state
      space that might 'represent' the current location of the rat, but that the
      ensemble 'looks ahead' during the rest of the cycle. Phase precession could
      result from intrinsic cellular dynamics involving interference of two oscillators
      of different frequencies, or from network interactions, similar to Hebb's 'phase
      sequence' concept, involving asymmetric synaptic connections. Both models have
      difficulties accounting for all of the available experimental data, however. A
      hybrid model, in which the look-ahead phenomenon implied by phase precession
      originates in superficial entorhinal cortex by some form of interference
      mechanism and is enhanced in the hippocampus proper by asymmetric synaptic
      plasticity during sequence encoding, seems to be consistent with available data,
      but as yet there is no fully satisfactory theoretical account of this phenomenon.
      This review is part of the INMED/TINS special issue Physiogenic and pathogenic
      oscillations: the beauty and the beast, based on presentations at the annual
      INMED/TINS symposium (http://inmednet.com).

PMID- 17532483
TI  - Synthesis and anti-HIV activity of (-)-beta-D-(2R,4R)-1,3-dioxolane-2,6-diamino
      purine (DAPD) (amdoxovir) and (-)-beta-D-(2R,4R)-1,3-dioxolane guanosine (DXG)
      prodrugs.
AB  - Prodrugs of (-)-beta-D-(2R,4R)-1,3-dioxolane-2,6-diamino purine (DAPD), organic
      salts of DAPD, 5'-L-valyl DAPD and N-1 substituted (-)-beta-D-(2R,4R)-1,3
      dioxolane guanosine (DXG) have been synthesized with the objective of finding
      molecules which might be superior to DAPD and DXG in solubility as well as
      pharmacologic profiles. Synthesized prodrugs were evaluated for anti-HIV activity
      against HIV-1(LAI) in primary human lymphocytes (PBM cells) as well as their
      cytotoxicity in PBM, CEM and Vero cells. DAPD prodrugs, modified at the C6
      position of the purine ring, demonstrated several folds of enhanced anti-HIV
      activity in comparison to the parent compound DAPD without increasing the
      toxicity. The presence of alkyl amino groups at the C6 position of the purine
      ring increased the antiviral potency several folds, and the most potent compound
      (-)-beta-D-(2R,4R)-1,3-dioxolane-2-amino-6-aminoethyl purine (8) was 17 times
      more potent than that of DAPD. 5'-L-Valyl DAPD 20 and organic acid salts 21-24
      also exhibited enhanced anti-HIV activity in comparison to DAPD, while DXG
      prodrugs 16 and 17 exhibited lower potency than that of DXG or DAPD.

PMID- 17532484
TI  - Concentrations of phytochelatins and glutathione found in natural assemblages of
      seaweeds depend on species and metal concentrations of the habitat.
AB  - The occurrence of the metal-complexing thiol peptides, phytochelatins (PC) in
      natural populations of brown, red and green seaweeds (marine macroalgae) was
      studied. Concentrations of PCs and their precursor glutathione (GSH) were
      measured in seaweeds collected from locations in south-west England with
      different levels of contamination by trace metals, to evaluate their role under
      natural environmental conditions. The non-protein thiols were identified and
      quantified in seaweed extracts by HPLC and the molecular structures of PCs were
      confirmed by LC-ESIMS. The capacity for production of PCs of representative
      seaweeds under Cd and Zn exposure was also assessed, experimentally. The
      concentrations of metals/metalloids (As, Cu, Cd, Pb and Zn) accumulated by the
      seaweeds were determined by ICP-MS. For the first time, PCs are reported in
      native Phaeophyceae (Fucus spp.), Rhodophyceae (Solieria chordalis) and
      Chlorophyceae (Rhizoclonium tortuosum) but not in thalli of Ulva spp. and Codium
      fragile (Chlorophyceae). The concentrations of PCs in brown and red seaweeds
      correlated with the contamination history of sampling sites and total metal
      burden of thalli. The highest concentrations of metals (5.6-7.1micromolg(-1) DW),
      PCs (200-240nmolSHg(-1)DW) and GSH (1,550-3,960nmolSHg(-1)DW), and the longest PC
      chain lengths (PC(2-4)) were found in Fucus spp. collected from the most
      contaminated site. A combination of PC-production and maintenance of high
      concentrations of GSH allows Fucus spp. and R. tortuosum (2,000nmolGSHg(-1)DW) to
      thrive in highly contaminated environments whereas in Ulva spp. high
      concentrations of GSH (1,000-1,500nmolSHg(-1)DW) together with thick cells walls
      and a high polysaccharide content appear to be responsible for metal-resistance.
      The lack of production of PCs in these green macroalgae suggests lower
      intracellular metal accumulation rather than an inability for synthesizing PCs.
      The higher concentrations of Cu (approximately 3.4micromolg(-1)DW) found in
      thallus of S. chordalis, compared with the Fucus spp. (1.5-2.4micromolg(-1)DW)
      from the same site, may induce stronger oxidative stress and result in lower
      concentrations of reduced glutathione (648nmolSHg(-1)DW) and PCs (70nmolSHg(
      1)DW). As a consequence S. chordalis at this site may have a lower resistance to
      metals and a more restricted distribution than the fucoids. Both fucoid species
      and the red seaweed Gracilaria gracilis, but not Ulva spp. or C. fragile, from
      low contaminated sites synthesized PCs under laboratory conditions when exposed
      to very high concentration of Cd. Our results clearly show that natural
      assemblages of seaweeds, belonging to disparate phylogenetic groups produce PCs
      when exposed to a mixture of metals in their environment. However, the
      involvement of thiol peptides in metal homeostasis, detoxification and resistance
      varies between seaweed species that are growing under the same environmental
      conditions.

PMID- 17532485
TI  - Involvement of the elicitor-induced gene OsWRKY53 in the expression of defense
      related genes in rice.
AB  - We present a detailed characterization of the chitin oligosaccharide elicitor
      induced gene OsWRKY53. OsWRKY53 was also induced in suspension-cultured rice
      cells by a fungal cerebroside elicitor and in rice plants by infection with the
      blast fungus Magnaporthe grisea. A fusion of OsWRKY53 with green fluorescent
      protein was detected exclusively in the nuclei of onion epidermal cells, and
      OsWRKY53 protein specifically bound to W-box elements. A transient assay using
      the particle bombardment method showed that OsWRKY53 is a transcriptional
      activator. A microarray analysis revealed that several defense-related genes,
      including pathogenesis-related protein genes such as PBZ1, were upregulated in
      rice cells overexpressing OsWRKY53. Finally, overexpression of OsWRKY53 in rice
      plants resulted in enhanced resistance to M. grisea. These results strongly
      suggest that OsWRKY53 is a transcription factor that plays important roles in
      elicitor-induced defense signaling pathways in rice.

PMID- 17532486
TI  - Baicalein inhibition of hydrogen peroxide-induced apoptosis via ROS-dependent
      heme oxygenase 1 gene expression.
AB  - In the present study, baicalein (BE) but not its glycoside, baicalin (BI),
      induced heme oxygenase-1 (HO-1) gene expression at both the mRNA and protein
      levels, and the BE-induced HO-1 protein was blocked by adding cycloheximide (CHX)
      or actinomycin D (Act D). Activation of ERK, but not JNK or p38, proteins via
      induction of phosphorylation in accordance with increasing intracellular peroxide
      levels was detected in BE-treated RAW264.7 macrophages. The addition of the ERK
      inhibitor, PD98059, (but not the p38 inhibitor, SB203580, or the JNK inhibitor,
      SP600125) and the chemical antioxidant, N-acetyl cysteine (NAC), significantly
      reduced BE-induced HO-1 protein expression by respectively blocking ERK protein
      phosphorylation and intracellular peroxide production. Additionally, BE but not
      BI effectively protected RAW264.7 cells from hydrogen peroxide (H(2)O(2))-induced
      cytotoxicity, and the preventive effect was attenuated by the addition of the HO
      inhibitor, SnPP, and the ERK inhibitor, PD98059. H(2)O(2)-induced apoptotic
      events including hypodiploid cells, DNA fragmentation, activation of caspase 3
      enzyme activity, and a loss in the mitochondrial membrane potential with the
      concomitant release of cytochrome c from mitochondria to the cytosol were
      suppressed by the addition of BE but not BI. Blocking HO-1 protein expression by
      the HO-1 antisense oligonucleotide attenuated the protective effect of BE against
      H(2)O(2)-induced apoptosis by suppressing HO-1 gene expression in macrophages.
      Overexpression of the HO-1 protein inhibited H(2)O(2)-induced apoptotic events
      such as DNA fragmentation and hypodiploid cells by reducing intracellular
      peroxide production induced by H(2)O(2), compared with those events in neo
      control (neo-RAW264.7) cells. In addition, CO, but not bilirubin and biliverdin,
      addition inhibits H(2)O(2)-induced cytotoxicity in macrophages. It suggests that
      CO can be responsible for the protective effect associated with HO-1
      overexpression. The notion of induction of HO-1 gene expression through a ROS
      dependent manner suppressing H(2)O(2)-induced cell death is identified in the
      present study.

PMID- 17532488
TI  - Uncommon adrenal masses: CT and MRI features with histopathologic correlation.
AB  - Adrenal glands are common sites of diseases. With dramatically increased use of
      computed tomography (CT) and magnetic resonance (MR) imaging, more and more
      uncommon adrenal masses have been detected incidentally at abdominal examinations
      performed for other purposes. In this article, uncommon adrenal masses are
      classified as cystic masses (endothelial cysts, epithelial cysts, parasitic
      cysts, and pseudocysts), solid masses (ganglioneuroma, ganglioneuroblastoma,
      extramedullary plasmacytoma (EMP), neurilemmoma, and lymphoma), fat-containing
      masses (myelolipoma, teratoma), and infectious masses (tuberculoma), and the
      imaging features of these uncommon masses are demonstrated. Although most of
      these lesions do not have specific imaging features, some fat-containing masses
      and cystic lesions present with characteristic appearances, such as myelolipoma,
      teratoma, and hydatid. Combination with histopathologic characteristic of these
      uncommon masses of adrenal gland, radiological features of these lesions on CT
      and MR imaging can be accurately understood with more confidences. Moreover, CT
      and MRI are highly accurate in localization of uncommon adrenal masses, and
      useful to guide surgical treatments.

PMID- 17532487
TI  - Ubiquitin-mediated degradation of Rpn4 is controlled by a phosphorylation
      dependent ubiquitylation signal.
AB  - A ubiquitylation signal of a protein substrate is defined as a short primary
      sequence or a structural feature recognized by a specific E3. Our previous work
      has mapped the ubiquitylation signal of Rpn4, the transcription activator for the
      Saccharomyces cerevisiae proteasome genes, to an N-terminal acidic domain (NAD)
      consisting of amino acids 211-229. However, the molecular mechanism by which
      Ubr2, the cognate E3, recognizes NAD remains unclear. Here we show that
      phosphorylation of either Ser-214 or Ser-220 enhances the binding of NAD to Ubr2.
      However, phosphorylation of Ser-220 but not Ser-214 plays a predominant role in
      Rpn4 ubiquitylation and degradation. Interestingly, NAD does not constitute the
      major Ubr2-binding site of Rpn4 even though it serves as the ubiquitylation
      signal essential for Rpn4 degradation. By contrast, the stable binding with Ubr2
      conferred by other domains of Rpn4 is not required for Rpn4 degradation. Our
      results indicate that ubiquitin-mediated degradation of Rpn4 is controlled by a
      phosphorylation-dependent ubiquitylation signal. This study also suggests that
      binding to E3 may be only a part of the function of a ubiquitylation signal.

PMID- 17532489
TI  - Correlates of plasma fibrinogen (FG) levels in a random sample of community
      dwelling elderly.
AB  - The aim of this study was to evaluate the association between plasma FG levels
      and coexisting cardiovascular diseases (CVD) risk factors, comorbidities,
      functional status and cognitive function in a random sample of 270 (163 women and
      107 men) community-dwelling elderly aged 65-79 years. The assessment included
      demographic and social variables, health status, nutritional state, physical and
      cognitive function. Physical activity was assessed by the Stanford Usual Activity
      Questionnaire. The average plasma FG level was lower in men 3.1+/-0.9 g/l (+/-SD)
      than in women 3.6+/-1.1g/l. In the whole group of elderly people, body mass index
      (BMI), percentage of body fat, calf circumference as well as total and low
      density cholesterol were positively correlated with FG levels, whereas the
      Stanford Moderate Index-negatively. Multifactor analysis of variance (ANOVA)
      revealed that female gender, calf circumference and the Stanford Moderate Index
      are the factors that independently predict FG levels. In conclusion, FG seems not
      to be related to functional status or cognitive function of older individuals.
      Nevertheless, our findings suggest that female gender, excess body fatness and
      low physical activity have an independent contribution to higher plasma FG levels
      in community-dwelling older subjects.

PMID- 17532490
TI  - Different effect of percutaneous and surgical coronary revascularization on
      cardiac autonomic function and inflammation in patients with stable angina.
AB  - We assessed heart rate variability (HRV) and high-sensitivity C-reactive protein
      (CRP) serum levels in 77 patients with chronic stable angina (CSA), 47 of whom
      had obstructive coronary artery disease (CAD) and 30 normal or near-normal
      coronary arteries (NCA). The effect of percutaneous coronary interventions (PCI)
      and bypass surgery (CABG) on HRV and CRP was assessed in 36 patients (18 PCI, 18
      CABG) 6 months after the intervention. A significant inverse correlation was
      found between CRP levels and HRV variables in CAD patients (best r value=-0.31,
      p=0.036 for very low frequency amplitude), but not in NCA patients. At follow-up,
      however, no significant correlation was found between CRP and HRV in PCI and CABG
      treated patients. Thus, while confirming the presence of a relation between
      cardiac autonomic dysfunction and inflammation in CAD patients, our data show
      that the association is lost after revascularization procedures.

PMID- 17532492
TI  - The bacterial P450 BM3: a prototype for a biocatalyst with human P450 activities.
AB  - The use of cytochrome P450 (P450 or CYP) enzymes as biocatalysts for the
      production of fine chemicals, including pharmaceuticals, has been of increasing
      interest, primarily owing to their catalytic diversity and broad substrate range.
      CYP102A1 (P450 BM3) from Bacillus megaterium integrates an entire monooxygenase
      system into one polypeptide and represents an appropriate prokaryotic model for
      industrial applications of mammalian P450 activities. CYP102A1 not only exhibits
      the highest catalytic activity ever detected in a P450 monooxygenase but also
      provides a potentially versatile biocatalyst for the production of human P450
      metabolites. CYP102A1 can be further engineered to be a drug-metabolizing enzyme,
      making it a promising candidate to use as a biocatalyst in drug discovery and
      synthesis.

PMID- 17532491
TI  - Efficient method for generation of bacteriophage insensitive mutants of
      Streptococcus thermophilus yoghurt and mozzarella strains.
AB  - Bacteriophage infection of Streptococcus thermophilus is becoming increasingly
      problematic in many industry fermentations such as yoghurt and mozzarella
      manufacture. This study describes the development of an efficient and rapid 3
      step approach for the generation of bacteriophage insensitive mutants (BIMs) of
      these starter strains. The method initially involves infection of a culture in
      solid media at a multiplicity of infection (M.O.I.) of 10 which is then incubated
      in milk overnight. BIMs are then isolated following successive rounds (20-25) of
      growth in 10% reconstituted skimmed milk (RSM) in the presence of high phage
      titres. The method selects for BIMs which can grow efficiently in milk. Using
      this approach BIMs of two industrial strains were generated, whose starter
      performance was comparable to the parent starters in terms of performance in
      milk. Genomic fingerprinting used to validate the identity of each BIM, revealed
      a number of restriction fragment length polymorphisms (RFLPs) in two of the
      resultant BIMs. This method provides a simple and reliable method for generation
      of BIMs of industrial starters which does not require any specialised equipment
      and should be widely applicable.

PMID- 17532493
TI  - Overview of brachytherapy resources in Europe: has brachytherapy still a place in
      treatment of cervix carcinomas?

PMID- 17532494
TI  - Evidence-based radiation oncology: definitive, adjuvant and salvage radiotherapy
      for non-metastatic prostate cancer.
AB  - The standard treatment options based on the risk category (stage, Gleason score,
      PSA) for localized prostate cancer include surgery, radiotherapy and watchful
      waiting. The literature does not provide clear-cut evidence for the superiority
      of surgery over radiotherapy, whereas both approaches differ in their side
      effects. The definitive external beam irradiation is frequently employed in stage
      T1b-T1c, T2 and T3 tumors. There is a pretty strong evidence that intermediate-
      and high-risk patients benefit from dose escalation. The latter requires
      reduction of the irradiated normal tissue (using 3-dimensional conformal
      approach, intensity modulated radiotherapy, image-guided radiotherapy, etc.).
      Recent data suggest that prostate cancer may benefit from hypofractionation due
      to relatively low alpha/beta ratio; these findings warrant confirmation though.
      The role of whole pelvis irradiation is still controversial. Numerous randomized
      trials demonstrated a clinical benefit in terms of biochemical control, local and
      distant control, and overall survival from the addition of androgen suppression
      to external beam radiotherapy in intermediate- and high-risk patients. These
      studies typically included locally advanced (T3-T4) and poor-prognosis (Gleason
      score >7 and/or PSA >20 ng/mL) tumors and employed
      neoadjuvant/concomitant/adjuvant androgen suppression rather than only adjuvant
      setting. The ongoing trials will hopefully further define the role of endocrine
      treatment in more favorable risk patients and in the setting of the dose
      escalated radiotherapy. Brachytherapy (BRT) with permanent implants may be
      offered to low-risk patients (cT1-T2a, Gleason score <7, or 3+4, PSA <or=10
      ng/mL), with prostate volume of <or=50 ml, no previous transurethral prostate
      resection and a good urinary function. Some recent data suggest a benefit from
      combining external beam irradiation and BRT for intermediate-risk patients. EBRT
      after radical prostatectomy improves disease-free survival and biochemical and
      local control rates in patients with positive surgical margins or pT3 tumors.
      Salvage radiotherapy may be considered at the time of biochemical failure in
      previously non-irradiated patients.

PMID- 17532495
TI  - A regional cooperative clinical study of radiotherapy for cervical cancer in east
      and south-east Asian countries.
AB  - PURPOSE: Radiotherapy differed widely in east and south-east Asia because of
      technical, cultural, and socio-economic differences. With the purpose of
      standardizing radiotherapy for cervical cancer in the region, an international
      clinical study was conducted. MATERIALS AND METHODS: Eleven institutions in eight
      Asian countries participated in the study. Between 1996 and 1998, 210 patients
      with stage IIIB cervical cancer were enrolled. Patients were treated with a
      combination of external beam radiotherapy (total dose, 50Gy) and either high-dose
      rate (HDR) or low-dose-rate (LDR) intracavitary brachytherapy (ICBT) according to
      the institutional practice. The planned point A dose was 20-28Gy/4 fractions for
      HDR-ICBT and 30-40Gy/1-2 fractions for LDR-ICBT. RESULTS: Hundred patients were
      treated with HDR-ICBT and 110 were treated with LDR-ICBT. The ICBT doses actually
      delivered to point A ranged widely: 12-32Gy in the HDR group and 26-52.7Gy in the
      LDR group. The 5-year follow-up rate among the countries differed greatly, from
      29% to 100%. The 5-year major complication rates were 6% in the HDR group and 10%
      in the LDR group. The 5-year overall survival rates were 51.1% in the HDR group
      and 57.5% in the LDR group. CONCLUSIONS: Although there were several problems
      with treatment compliance and patients' follow-up, the study suggests that the
      protocols provided favorable outcomes with acceptable rates of late complications
      in the treatment of advanced cervical cancer in east and south-east Asia.

PMID- 17532496
TI  - Influence of contrast materials on dose calculation in radiotherapy planning
      using computed tomography for tumors at various anatomical regions: a prospective
      study.
AB  - Influences of iodinated contrast media on dose calculation were studied in 26
      patients. Mean increases in monitor units by contrast media administration were
      less than 1% and considered negligible in planning of whole-brain, whole-neck,
      mediastinal, and whole-pelvic irradiation. However, mean increases over 2% were
      seen in planning of upper-abdominal radiotherapy.

PMID- 17532497
TI  - Molecular methods for the detection of biogenic amine-producing bacteria on
      foods.
AB  - Biogenic amines are low molecular weight organic bases that can be detected in
      raw and processed foods. Several toxicological problems resulting from the
      ingestion of food containing biogenic amines have been described. Biogenic amines
      are mainly produced by the decarboxylation of certain amino acids by microbial
      action. Since the ability of microorganisms to decarboxylate amino acid is highly
      variable, being in most cases strain-specific, the detection of bacteria
      possessing amino acid decarboxylase activity is important to estimate the risk of
      biogenic amine food content and to prevent biogenic amine accumulation in food
      products. Molecular methods for the early and rapid detection of these producer
      bacteria are becoming an alternative to traditional culture methods. PCR methods
      offer the advantages of speed, sensitivity, simplicity and specific detection of
      amino acid decarboxylase genes. Moreover, these molecular methods detect
      potential biogenic amine risk formation in food before the amine is produced. The
      aim of the present review is to give a complete overview of the molecular methods
      proposed in the literature for the detection of biogenic amine-producing
      bacteria. These genetic procedures allow the introduction of early control
      measures to avoid the development of these bacteria.

PMID- 17532498
TI  - Pharmacoeconomics of therapy for Guillain-Barre syndrome: plasma exchange and
      intravenous immunoglobulin.
AB  - Guillain-Barre syndrome (GBS) is an acute neuropathy and a clinical syndrome that
      includes a number of pathological and electrophysiological subtypes. Intravenous
      immunoglobulin (IVIG) and plasma exchange (PE) are both equally efficacious for
      the treatment of GBS; however, the cost of IVIG may be lower for both the patient
      and the healthcare system. To compare the pharmacoeconomics of PE and IVIG in
      GBS, a retrospective study was done from 1999 to 2004, which included a total of
      24 patients with GBS who were admitted to Taipei Veterans General Hospital. This
      showed that except for the costs of the drugs used in IVIG, treatment of GBS with
      IVIG was more cost-effective (p=0.057) than that with PE in total length of
      hospitalization and the cost of procedures and hospitalization. The study also
      showed that the total costs were higher for patients on ventilators than those
      not requiring ventilators (p=0.008, t-test) and the length of hospitalization
      showed a very strong linear relationship to total costs (Pearson correlation
      coefficient=0.907). The regression analysis showed that each additional day of
      hospitalization increased the hospitalization costs by an average of 5599 New
      Taiwan Dollars (NT) (US$1.00=NT$33.50 in 2005).

PMID- 17532499
TI  - Anterior cervical discectomy and fusion: analysis of surgical outcome with and
      without plating.
AB  - The aim of this study is to analyse the differences in clinical and radiological
      outcome of anterior cervical discectomy and fusion for cervical degenerative
      disease, with and without the addition of an anterior cervical locking plate.
      Although disc arthoplasty is gaining popularity, the anterior cervical
      decompression and fusion procedure remains the gold standard. The outcome of 242
      cases operated between 1991 to 1998 were analysed. Two groups of patients were
      operated on by the same surgeon. The only difference in technique between the two
      groups was the addition of an anterior cervical plate, with all other technical
      details matching, including the use of iliac crest autograft. The indications for
      surgery for both groups was identical. We made an attempt to study radiological
      fusion, clinical outcome and complications between the non-plated and plated
      groups. Our main finding is that the addition of an anterior plate reduces the
      number of poor clinical outcomes, but does not increase the number of excellent
      outcomes. Anterior discectomy and fusion with plating in our series had a
      significantly higher fusion rate; 98% fusion was noted in the plating group as
      compared to 93.5% in the non-plating group (Fisher's exact test, p=0.029). Union
      was faster in the plated group with no significant increase in surgical
      complications. Although clinical outcomes were superior in the plated group for
      the radiculopathy cohort, excellent outcomes were not significantly higher as
      compared to the non-plated group. The non-plated group had a significantly higher
      rate of poor outcomes, with 10% of patients requiring revision surgery for non
      union, kyphosis, graft extrusion and graft collapse with foraminal stenosis. 1.8%
      of the plated group required revision surgery.

PMID- 17532500
TI  - Surgical and hardware complications in subthalamic nucleus deep brain
      stimulation.
AB  - OBJECTIVE: To assess the surgical and hardware complications in 26 consecutive
      patients with movement disorders undergoing subthalamic deep brain stimulation
      (STN-DBS) in early practice at our institute. METHODS: The 26 patients in our
      institute were analyzed retrospectively. Group A included the first eight
      patients treated while we had no facility for microelectrode recording (MER), 16
      intracranial procedures were performed and 8 batteries were implanted. Group B
      (with MER) included 18 patients, 35 intracranial procedures were performed and 18
      batteries were implanted. RESULTS: The intracranial morbidity was 18.75% in group
      A and 5.71% in group B. The extracranial morbidity was 37.5% in group A and
      16.67% in group B. There was no hardware-related infection in our study. The
      overall mortality rate was 7.69%, and deaths were not surgical related.
      CONCLUSIONS: The associated morbidity is significant in STN-DBS. The use of MER
      may improve the clinical outcome while decreasing the morbidity.

PMID- 17532501
TI  - Endothelin-1 and cerebral blood flow in a porcine model.
AB  - The purpose of the study was to investigate whether provoked changes of cerebral
      perfusion pressure and arterial carbon dioxide tension are able to influence the
      cerebral metabolism of endothelin-1 (ET-1) in a porcine model. Brain tissue
      oxygen tension, regional cerebral blood flow and mean arterial blood pressure
      were monitored in 10 healthy pigs during induced hyperventilation (HV),
      hypertension (HrT) and hypotension (HoT). ET-1 was determined in the arterial and
      cerebrovenous blood. Microdialysis samples (lactate, glucose and pyruvate) were
      taken from brain and subcutaneous tissue. A significant decrease (p<0.05) of the
      arterial ET-1 (1.46+/-0.33 fmol/mL) compared to the baseline (2.18+/-0.36
      fmol/mL) was observed after the HoT-period. We detected a positive correlation
      between cerebrovenous ET-1 and extracellular cerebral glucose (0.68; p<0.05)
      after the baseline as well as a negative correlation of -0.81 (p<0.005) between
      the cerebrovenous ET-1 level and the extracellular cerebral lactate after the HoT
      period. These data imply that with increasingly pathological changes of the
      cerebral metabolism endothelin becomes progressively more important in the
      regulation of cerebral vascular tone.

PMID- 17532502
TI  - Comparative neuroprotective effect of sodium channel blockers after experimental
      spinal cord injury.
AB  - Spinal cord injury (SCI) results in loss of function below the lesion. Secondary
      injury following the primary impact includes a number of biochemical and cellular
      alterations leading to tissue necrosis and cell death. Influx of Na(+) ions into
      cells has been postulated to be a key early event in the pathogenesis of
      secondary traumatic and ischemic central nervous system injury. Previous studies
      have shown that some voltage-sensitive sodium channel blockers provide powerful
      neuroprotection. The purpose of the present study was to compare the
      neuroprotective effect of three sodium channel blockers-mexiletine, phenytoin and
      riluzole--after SCI. Ninety rats were randomly and blindly divided into five
      groups of 18 rats each: sham-operated group, trauma group (bolus injection of 1
      mL physiological saline intraperiteonally [i.p.]), mexiletine treatment group (80
      mg/kg, i.p.), phenytoin treatment group (200 mg/kg, i.p.) and riluzole treatment
      group (8 mg/kg, i.p.). Twenty-four hours after injury, the rats were killed for
      determination of spinal cord water content and malondialdehyde (MDA) levels.
      Motor function scores of six rats from each group were evaluated weekly for six
      weeks. Then the rats were killed for histopathological assessment. Although all
      the treatment groups revealed significantly lower MDA levels and spinal cord
      edema than the trauma group (p<0.05), the riluzole and mexiletine treatment
      groups were better than the phenytoin treatment group. In the chronic stage,
      riluzole and mexiletine treatment achieved better results for neurobehavioral and
      histopathological recovery than phenytoin treatment. In conclusion, all the
      tested Na(+) blockers had a neuroprotective effect after SCI; riluzole and
      mexiletine were superior to phenytoin.

PMID- 17532503
TI  - Symptomatic tension pneumocephalus: an unusual post-operative complication of
      posterior spinal surgery.
AB  - Pneumocephalus is a rare, but serious complication of spinal surgery and its
      management and physiology is not widely recognized. Symptomatic tension
      pneumocephalus secondary to iatrogenic cerebrospinal fluid (CSF) leak after
      surgical intervention, and drainage with a vacuum suction device, has not been
      previously reported. We report a patient who underwent intervertebral disc
      surgery who developed pneumoencephalus after drainage with a vacuum suction
      device. Imaging showed significant pneumocephalus in the subarachnoid space of
      the frontal region and in the cisterns. The condition was resolved by
      discontinuation of the suction drainage, bed rest and hyperhydration. Thus,
      spinal drainage may predispose to entry of air intracranially and pneumocephalus.
      It is important to be aware of this serious post-operative complication in
      patients with a CSF fistula.

PMID- 17532504
TI  - Melanotic schwannoma.
AB  - BACKGROUND: Melanotic schwannomas are tumors of Schwann cell origin,
      characterized by cytoplasmic deposition of melanin. Melanotic schwannomas are
      rare. Description of the course of these tumors differs somewhat, but it is
      generally considered a benign lesion. CLINICAL PRESENTATION: A 54-year-old man
      presented with hypoesthesia, pain and weakness of the right arm and leg for 4
      months. An MRI scan revealed an intradural extramedullary lesion at the level of
      the foramen magnum and C1. OPERATION: Total resection of the mass was performed.
      A diagnosis of melanotic schwannoma was made based on histologic morphology and
      the immunohistochemical profile. Over a 2-year follow-up period there has been no
      local recurrence. CONCLUSION: Melanotic schwannoma is a rare variant of
      schwannoma composed of melanin-producing cells with ultrastructural features of
      Schwann cells. Distinguishing between this tumor and malignant melanoma is
      important in planning management. Total resection should be performed.
      Appropriate long-term follow-up is needed for all melanotic schwannomas.

PMID- 17532505
TI  - Complete coding sequences and phylogenetic analysis of Human Bocavirus (HBoV).
AB  - Human Bocavirus (HBoV) is a novel virus which can cause respiratory tract disease
      in infants or children. Recently, the prevalence of this virus has been studied
      worldwide. In this study, 18 of 252 (7.14%) nasopharyngeal suctions from infants
      or children between 1 month and 9 years of age with respiratory tract illness
      were HBoV-positive by PCR. Three positive samples were selected for sequencing
      the entire coding sequences using a new conserved set of primers. The results
      showed that the most conserved regions of HBoV are the NS1 and NP1 genes, whereas
      VP1 and VP2 showed frequent variations. However, the complete coding sequences
      showed that the variations did not depend on the origin of virus found. The
      complete coding sequences determined in this study can resolve the problem of an
      HBoV detection method, which can be advantageously implemented in laboratory
      detection.

PMID- 17532507
TI  - Defining SH2 domain and PTP specificity by screening combinatorial peptide
      libraries.
AB  - Src homology 2 (SH2) domains mediate protein-protein interactions by recognizing
      short phosphotyrosyl (pY) peptide motifs in their partner proteins. Protein
      tyrosine phosphatases (PTPs) catalyze the dephosphorylation of pY proteins,
      counteracting the protein tyrosine kinases. Both types of proteins exhibit
      primary sequence specificity, which plays at least a partial role in dictating
      their physiological interacting partners or substrates. A combinatorial peptide
      library method has been developed to systematically assess the sequence
      specificity of SH2 domains and PTPs. A "one-bead-one-compound" pY peptide library
      is synthesized on 90-microm TentaGel beads and screened against an SH2 domain or
      PTP of interest for binding or catalysis. The beads that carry the tightest
      binding sequences against the SH2 domain or the most efficient substrates of the
      PTP are selected by an enzyme-linked assay and individually sequenced by a
      partial Edman degradation/mass spectrometry technique. The combinatorial method
      has been applied to determine the sequence specificity of 8 SH2 domains from Src
      and Csk kinases, adaptor protein Grb2, and phosphatases SHP-1, SHP-2, and SHIP1
      and a prototypical PTP, PTP1B.

PMID- 17532508
TI  - Design, preparation and use of ligated phosphoproteins: a novel approach to study
      protein phosphatases by dot blot array, ELISA and Western blot assays.
AB  - The study of substrate specificity of protein phosphatases (PPs) is very
      challenging since it is difficult to prepare a suitable phosphorylated substrate.
      Phosphoproteins, phosphorylated by a protein kinase, or chemically synthesized
      phosphopeptides are commonly used substrates for PPs. Both types of these
      substrates have their advantages and limitations. Phosphoproteins mimic more
      closely the physiologically relevant PP substrates, but their preparation is
      technically demanding. Synthetic phosphopeptides present advantages over proteins
      because they can be easily produced in large quantity and their amino acid
      sequence can be designed to contain potential determinants of substrate
      specificity. However, short peptides are less optimal compared to in vivo PP
      substrates and often display poor and variable binding to different matrices,
      resulting in low sensitivity in analysis of PP activity on solid support. In this
      work we utilize the intein-mediated protein ligation (IPL) technique to generate
      substrates for PPs, combining the advantages of proteins and synthetic peptides
      in one molecule. The ligation of a synthetic phosphopeptide to an intein
      generated carrier protein (CP) with a one-to-one stoichiometry results in the
      formation of a ligated phosphoprotein (LPP). Three widely used assays, dot blot
      array, Western blot and ELISA were employed to study the PP activity on LPP
      substrates. Dephosphorylation was measured by detection of the remaining
      phosphorylation, or lack of it, with a phospho-specific antibody. The data show
      the advantage of LPPs over free peptides in assays on solid supports. LPPs
      exhibited enhanced binding to the matrices used in the study, which significantly
      improved sensitivity and consistency of the assays. In addition, saturation of
      the signal was circumvented by serial dilution of the assay samples. This report
      describes detailed experimental procedures for preparation of LPP substrates and
      their use in PP assays based on immobilization on solid supports.

PMID- 17532509
TI  - Application of hydrogen/deuterium exchange mass spectrometry to study protein
      tyrosine phosphatase dynamics, ligand binding, and substrate specificity.
AB  - Protein tyrosine phosphatases (PTPs) are signaling enzymes that control a diverse
      array of cellular processes. Further insight into the specific functional roles
      of PTPs in cellular signaling requires detailed understanding of the molecular
      basis for substrate recognition by the PTPs. A central question is how PTPs
      discriminate between multiple structurally diverse substrates that they encounter
      in the cell. Although X-ray crystallography is capable of revealing the intimate
      structural details for molecular interaction, structures of higher order
      PTP.substrate complexes are often difficult to obtain. Hydrogen/deuterium
      exchange mass spectrometry (H/DX-MS) is a powerful tool for mapping protein
      protein interfaces, as well as identifying conformational and dynamic
      perturbations in proteins. In addition, H/DX-MS enables analysis of large protein
      complexes at physiological concentrations and provides insight into the solution
      behavior of these complexes that can not be gleaned from crystal structures. We
      have utilized H/DX-MS to probe PTP dynamics, ligand binding, and the structural
      basis of substrate recognition. In this article, we review general principles of
      H/DX-MS technology as applied to study protein-protein interactions and dynamics.
      We also provide protocols for H/DX-MS successfully used in our laboratory to
      define the molecular basis of ERK2 substrate recognition by MKP3. Many of the
      aspects that we cover in detail should be applicable to the study of other PTPs
      with their specific targets.

PMID- 17532510
TI  - Analyzing protein tyrosine phosphatases by phosphotyrosine analog integration.
AB  - Reversible protein phosphorylation plays a central role in cellular signal
      transduction and is a focus of biomedical studies. However, it is a challenging
      task to study the effects of protein phosphorylation in the presence of protein
      phosphatase activities, especially for protein tyrosine phosphatases SHP1, SHP2
      and LMW-PTP, which are themselves regulated by protein tyrosine phosphorylation.
      Expressed protein ligation, by combining chemical peptide synthesis with
      recombinant protein expression, allows for site-specific unnatural modifications
      of semisynthetic proteins. In this review, we describe how semisynthetic proteins
      were prepared to incorporate nonhydrolyzable phosphotyrosine analogs, and
      utilized in combination with site-directed mutagenesis and other means to
      elucidate regulatory mechanisms of protein tyrosine phosphatases.

PMID- 17532511
TI  - Mass spectrometry-based analyses for identifying and characterizing S
      nitrosylation of protein tyrosine phosphatases.
AB  - All members in the protein tyrosine phosphatase (PTP) family of enzymes contain
      an invariant Cys residue which is absolutely indispensable for catalysis. Due to
      the unique microenvironment surrounding the active center of PTPs, this Cys
      residue exhibits an unusually low pKa characteristic, thus being highly
      susceptible to oxidation or S-nitrosylation. While oxidation-dependent regulation
      of PTP activity has been extensively examined, the molecular details and
      biological consequences of PTP S-nitrosylation remain unexplored. We hypothesized
      that the catalytic Cys residue is targeted by proximal nitric oxide (NO) and its
      derivatives collectively termed reactive nitrogen species (RNS), leading to
      nitrosothiol formation concomitant with reversible inactivation of PTPs. To test
      this hypothesis, we have developed novel strategies to examine the redox status
      of Cys residues of purified PTP1B that was exposed to NO donor S-Nitroso-N
      penicillamine (SNAP). A gel-based method in conjunction with mass spectrometry
      (MS) analysis revealed that the catalytic Cys215 of PTP1B was reversibly modified
      when PTP1B was briefly treated with SNAP. In order to further identify the exact
      mode of NO-induced modification, we employed an online LC-ESI-MS/MS analysis
      incorporating a mass difference-based, data-dependent acquisition function that
      effectively mapped the S-nitrosylated Cys residues. Our results demonstrated that
      treating PTP1B with SNAP led to S-nitrosothiol formation of the catalytic Cys215.
      Interestingly, SNAP-induced modifications were strictly reversible as highly
      oxidized Cys derivatives (Cys-SO(2)H or Cys-SO(3)H) were not identified by MS
      analyses. Thus, the methods introduced in this study provide direct evidence to
      prove the direct link between S-nitrosylation of the catalytic Cys residue and
      reversible inactivation of PTPs.

PMID- 17532512
TI  - Strategies for developing protein tyrosine phosphatase inhibitors.
AB  - Protein tyrosine phosphatases (PTPs) play vital roles in numerous cellular
      processes and are implicated in a growing number of human diseases, ranging from
      cancer to cardiovascular, immunological, infectious, neurological, and metabolic
      diseases. Here we present methods for developing small molecule inhibitors for
      these enzymes, starting with how to set up a high throughput chemical library
      screening for PTP inhibitors, how to confirm and prioritize hits, and how to
      circumnavigate possible pitfalls. Next, we present the relatively new hit
      generating method of in silico or virtual screening. We give an overview of
      existing software tools, describe how to choose and generate protein target
      structures and illustrate the procedure with examples. We then discuss how three
      dimensional PTP structures can be analyzed in terms of their potential to bind
      small molecule inhibitors selectively over homologous proteins and how computer
      tools can be applied for lead optimization efforts. We finish with a perspective
      of how well these PTP inhibitors might perform as future drugs to treat human
      disease.

PMID- 17532513
TI  - An affinity-based fluorescence polarization assay for protein tyrosine
      phosphatases.
AB  - Protein tyrosine phosphatases (PTPs) are important signaling enzymes that control
      such fundamental processes as proliferation, differentiation, survival/apoptosis,
      as well as adhesion and motility. Potent and selective PTP inhibitors serve not
      only as powerful research tools, but also as potential therapeutics against a
      variety illness including cancer and diabetes. PTP activity-based assays are
      widely used in high throughput screening (HTS) campaigns for PTP inhibitor
      discovery. These assays suffer from a major weakness, in that the reactivity of
      the active site Cys can cause serious problems as highly reactive oxidizing and
      alkylating agents may surface as hits. We describe the development of a
      fluorescence polarization (FP)-based displacement assay that makes the use of an
      active site Cys to Ser mutant PTP (e.g., PTP1B/C215S) that retains the wild-type
      binding affinity. The potency of library compounds is assessed by their ability
      to compete with the fluorescently labeled active site ligand for binding to the
      Cys to Ser PTP mutant. Finally, the substitution of the active site Cys by a Ser
      renders the mutant PTP insensitive to oxidation and alkylation and thus will
      likely eliminate "false" positives due to modification of the active site Cys
      that destroy the phosphatase activity.

PMID- 17532514
TI  - Implementation of high-content assay for inhibitors of mitogen-activated protein
      kinase phosphatases.
AB  - Small molecule inhibitors of protein tyrosine kinases have become both powerful
      chemical probes of biological processes and clinically effective therapeutics. In
      contrast, few small molecule inhibitors of protein tyrosine phosphatases have
      been identified and none are currently approved for clinical use. New cell-based
      high-content methods have been developed that should enable investigators to
      probe for selective inhibitors of diseases-relevant protein phosphatases. Details
      of these methods are described herein.

PMID- 17532516
TI  - Soluble nanopolymer-based phosphoproteomics for studying protein phosphatase.
AB  - Protein phosphorylation is a vital reversible post-translational modification
      that regulates protein-protein interactions, enzymatic activity, subcellular
      localization, complex formation and protein stability. The emerging field of mass
      spectrometry-based proteomics allows us to investigate phosphorylation and
      dephosphorylation on a global scale. In this review, we describe a new strategy
      based on soluble nanopolymers that have been used to selectively isolate
      phosphopeptides for mass spectrometric analysis. Functionalized soluble
      nanopolymers provide a homogeneous environment and linear reaction kinetics for
      chemical derivatization to isolate phosphopeptides with high specificity.
      Combined with phosphatase inhibitors and stable isotopic labeling, the approach
      has the capability of quantitatively measuring phosphorylation and
      dephosphorylation on individual sites. We provide experimental details for the
      approach and describe some other complementary techniques that can be used.

PMID- 17532515
TI  - Generation of inhibitor-sensitive protein tyrosine phosphatases via active-site
      mutations.
AB  - Protein tyrosine phosphatases (PTPs) catalyze the dephosphorylation of
      phosphotyrosine, a central control element in mammalian signal transduction.
      Small-molecule inhibitors that are specific for each cellular PTP would be
      valuable tools in dissecting phosphorylation networks and for validating PTPs as
      therapeutic targets. However, the common architecture of PTP active sites impedes
      the discovery of selective PTP inhibitors. Our laboratory has recently used
      enzyme/inhibitor-interface engineering to generate selective PTP inhibitors. The
      crux of the strategy resides in the design of "inhibitor-sensitized" PTPs through
      protein engineering of a novel binding pocket in the target PTP. "Allele
      specific" inhibitors that selectively target the sensitized PTP can be
      synthesized by modifying broad-specificity inhibitors with bulky chemical groups
      that are incompatible with wild-type PTP active sites; alternatively, specific
      inhibitors that serendipitously recognize the sensitized PTP's non-natural pocket
      may be discovered from panels of "non-rationally" designed compounds. In this
      review, we describe the current state of the PTP-sensitization strategy, with
      emphases on the methodology of identifying PTP-sensitizing mutations and
      synthesizing the compounds that have been found to target PTPs in an allele
      specific manner. Moreover, we discuss the scope of PTP sensitization in regard to
      the potential application of the approach across the family of classical PTPs.

PMID- 17532517
TI  - Affinity-purification mass spectrometry (AP-MS) of serine/threonine phosphatases.
AB  - Association of serine/threonine phosphatases with regulatory proteins is a key
      component of their specificity, and the identification of these binding partners
      is critical to understanding phosphatases function and regulation. Affinity
      purification/mass spectrometry (AP-MS) approaches have been and continue to be
      instrumental in identifying these interactors. Here, we review the general
      principles of AP-MS, and present two affinity-purification protocols compatible
      with subsequent mass spectrometry, namely FLAG purification, and the tandem
      affinity purification (TAP). We have successfully used these protocols for the
      identification of binding partners for PP2A, PP4 and PP6, and they should be
      amenable to the analysis of interactors for other phosphatases.

PMID- 17532518
TI  - PTPome-wide functional RNA interference screening methods.
AB  - The elucidation of the entire complement of genes encoding protein tyrosine
      phosphatases (PTPs) in human genome, the human 'PTPome', has made it possible to
      experimentally address the entire family in an unbiased manner. Here we describe
      a functional RNA interference-based assay, in which we evaluate 87 of the known
      107 PTPs for effects on cell survival in a high throughput manner. The details of
      assay rationale and design, instrumentation, pitfalls, data analysis, and further
      validation steps are described. We also discuss the suitability of this
      technology for further assay development and application to other functional read
      outs and signaling pathways.

PMID- 17532519
TI  - Gelatin microspheres encapsulated with a nonpeptide angiogenic agent, ginsenoside
      Rg1, for intramyocardial injection in a rat model with infarcted myocardium.
AB  - Angiogenic therapies may need to select a stable agent to be delivered. In the
      study, a nonpeptide angiogenic agent, ginsenoside Rg(1) (Rg(1)), was encapsulated
      in the gelatin microspheres (MSs) crosslinked with genipin and intramuscularly
      injected into a rat model with infarcted myocardium. bFGF was used as a control.
      After swelling in an aqueous environment, the MSs without crosslinking became
      collapsed and stuck together. For those crosslinked, the swollen MSs appeared to
      be more stable with an increasing the degree of crosslinking. After it was
      released from MSs in vitro, the remaining activity of bFGF on HUVEC proliferation
      reduced significantly, while that of Rg(1) remained constant. An inspection of
      the retrieved hearts revealed a large aneurysmal left ventricle (LV) with a
      thinned myocardium and a significant myocardial fibrosis for that treated with
      the Empty MSs (without drug encapsulation). However, those receiving the MSs
      encapsulated with bFGF or Rg(1) attenuated the enlargement of the LV cavity and
      the development of myocardial fibrosis. The densities of microvessels found in
      the border zones of the infarct treated with the bFGF or Rg(1) MSs were
      significantly greater than that treated with the Empty MSs. These results
      indicated that Rg(1), a stable angiogenic agent, successfully enhanced the
      myocardial perfusion and preserved the infarcted LV function.

PMID- 17532520
TI  - Nanotechnology: What it can do for drug delivery.

PMID- 17532521
TI  - Training programs for children: literature review.
AB  - INTRODUCTION: Training programs are increasingly being prescribed for
      occupational therapy for adults affected by chronic illness and/or handicap, but
      their use is more recent for children and teenagers. OBJECTIVE: A review of the
      literature to synthesize information concerning training programs for children,
      whether healthy or with disease or handicap, considering the target population,
      methodology, the results and limitations. METHODS: We searched the Medline
      database with use of the key words retraining, training, training programs,
      physical activity, physical training, fitness program, sport, children,
      disability, and handicap. We also searched references of the selected articles
      for appropriate studies. DISCUSSION/CONCLUSION: Physical activity seems to be a
      good means of primary preventing adverse health in the healthy child and
      secondary prevention in children with chronic disease or handicap. Thus, training
      programs could be adapted and integrated into the global treatment of sick or
      handicapped children in the health care situation or in the home. These programs
      are feasible and do not undermine children's health, but few studies have shown
      clear data on the methods of the programs. The suggested training programs, not
      always validated, included two to five sessions from 30 to 60 min/week, for 6-16
      weeks, of variable activity and intensity, adapted to the condition and the
      objectives of therapy. Training programs adapted to children should be validated
      to allow their accessibility by health care professionals dealing with children
      with chronic disease and/or handicap.

PMID- 17532522
TI  - Diabetes prevalence and association with social status--widening of a social
      gradient? German national health surveys 1990-1992 and 1998.
AB  - BACKGROUND: Widening of social inequality in health is often discussed. Data
      regarding trends of the association between diabetes prevalence and social status
      are lacking. METHODS: Using two German health surveys (age 25-69 years), we
      estimated diabetes prevalences in 1998 compared to 1990-1992. Interaction of
      secular time with educational level, adjusted for age and BMI, were estimated in
      men and women using multiple regression models, considering the sample design.
      RESULTS: Diabetes prevalences in 1990-1992 and 1998 were 5.1% (95% CI 4.1-6.0)
      and 4.3% (3.5-5.1) in men, and 4.7% (4.0-5.4) and 3.8% (3.0-4.6) in women. It was
      significantly higher in older subjects and in obese subjects, and tended to be
      higher in lower educated subjects. Overall, prevalence tended to be lower in 1998
      compared to 1990-1992, however, not statistically significant after adjustment
      for education and BMI (odds ratio, 95% CI: men 0.73; 0.39-1.37; women 0.41; 0.17
      1.03). On a descriptive level, in the lowest education group, the diabetes
      prevalence was higher in 1998 compared to 1990-1992, whereas, it has decreased in
      higher educated subjects. However, confidence intervals were large, and we found
      no statistically significant interaction between calendar year and the
      educational level. CONCLUSIONS: Diabetes prevalence tended to decrease in Germany
      during the 1990s. A widening of social disparity in diabetes risk might be
      present, but a significant increase could not be confirmed.

PMID- 17532525
TI  - A multilayered defense against infection: combinatorial control of insect immune
      genes.
AB  - The innate immune defense system involves the activity of endogenous
      antimicrobial peptides (AMPs), which inhibit the growth of most microbes. In
      insects, genes encoding AMPs are expressed at basal levels in barrier epithelia
      and are upregulated systemically in response to infection. To achieve this
      differentiated immune defense, Drosophila immune gene promoters combine tissue
      specific enhancers and signal-dependent response elements. Transcription factors
      of the Hox, POU and GATA families control tissue-specific expression of AMP
      genes, either constitutively or in combination with NF-kappaB/Rel family factors
      that function as 'on-off switches' during infection. Here, we review these
      different modes of AMP expression and provide a model for transcriptional
      regulation of AMP genes.

PMID- 17532523
TI  - Oral resiquimod in chronic HCV infection: safety and efficacy in 2 placebo
      controlled, double-blind phase IIa studies.
AB  - BACKGROUND/AIMS: To explore safety, pharmacokinetics, and pharmacodynamics of
      oral administration of resiquimod, a Toll-like receptor 7 and 8 agonist that
      induces endogenous interferon-alpha, in subjects with chronic hepatitis C virus
      infection. METHODS: Two randomized, double-blind phase IIa studies of resiquimod
      administered two times per week for 4 weeks. Multicenter study (U.S.): 12
      subjects received resiquimod 0.01 mg/kg and 4 received placebo. Single center
      study (France): 6 subjects received 0.01 mg/kg, 11 received 0.02 mg/kg and 6
      received placebo. RESULTS: Resiquimod 0.01 mg/kg was tolerated; two 0.2 mg/kg
      subjects discontinued treatment. More subjects reported severe grade adverse
      events at 0.02 mg/kg; events were consistent with systemic cytokine induction,
      including fever, headache, shivering, and lymphopenia. Mean maximum serum
      resiquimod concentrations were 3.82+/-1.47 and 7.55+/-4.17 ng/mL for 0.01 mg/kg
      and 0.02 mg/kg, respectively. At 0.02 mg/kg, two, three and one subjects had
      maximal reductions in viral levels of at least 1-, 2- and 3-logs, respectively;
      reductions were generally transient. Interferon-alpha levels appeared correlated
      with decreases in viral titer and lymphocyte counts, as well as increase in
      neutrophil counts. CONCLUSIONS: Oral administration of resiquimod 0.02 mg/kg
      transiently reduced viral levels but was associated with adverse effects similar
      to interferon-alpha.

PMID- 17532526
TI  - The pan-genome: towards a knowledge-based discovery of novel targets for vaccines
      and antibacterials.
AB  - During the past decade, sequencing of the entire genome of pathogenic bacteria
      has become a widely used practice in microbiology research. More recently,
      sequence data from multiple isolates of a single pathogen have provided new
      insights into the microevolution of a species as well as helping researchers to
      decipher its virulence mechanisms. The comparison of multiple strains of a single
      species has resulted in the definition of the species pan-genome, as a measure of
      the total gene repertoire that can pertain to a given microorganism. This concept
      can be exploited not only to study the diversity of a species, but also, as we
      discuss here, to provide the opportunity to use a knowledge-based approach for
      the development of novel vaccine candidates and new-generation targets for
      antimicrobials.

PMID- 17532528
TI  - Identifying and validating novel targets with in vivo disease models: guidelines
      for study design.
AB  - In vivo studies are an important tool for the identification and validation of
      novel drug targets in medicine; however, the interpretation of submitted and
      published data is often compromised by inadequate study design. Different study
      protocols, including the number of control groups and group size calculations,
      differ in target identification and validation studies. Furthermore, animal
      studies require that the selected target or compound meets the requirements for
      species specificity and target specificity; thus, providing the rationale for the
      selection of a particular species, strain, gender and age of the animals is
      necessary. Altogether, the presentation of target validation studies should meet
      defined criteria similar to those used in human trials.

PMID- 17532527
TI  - Orphan nuclear receptors in drug discovery.
AB  - Orphan nuclear receptors provide a unique resource for uncovering novel
      regulatory systems that impact human health and also provide drug targets for a
      variety of human diseases. Ligands of nuclear receptors have been used in several
      important therapeutic areas, such as breast cancers, skin disorders and diabetes.
      Orphan nuclear receptors, therefore, represent a tremendous opportunity in
      understanding and treating human diseases. Here, I highlight recent advances in
      the use of orphan nuclear receptors and their potential as targets for drug
      discovery in diabetes, obesity, neurodegenerative diseases and other related
      disorders.

PMID- 17532529
TI  - Prediction of microRNA targets.
AB  - Recently, microRNAs (miRNAs) have been shown to be important regulators of genes
      in many organisms and have already been implicated in a growing number of
      diseases. MiRNAs are short (21-23 nucleotides) RNAs that bind to the 3'
      untranslated regions of target genes. This binding event causes translational
      repression of the target gene and, evidence now suggests, also stimulates rapid
      degradation of the target transcript. miRNAs represent a new species of
      regulator, controlling the levels of potentially large numbers of proteins, many
      of which might be important drug targets. The expression of miRNAs shows that
      they are highly differentially expressed, with specific miRNAs active in certain
      tissues at certain times. In many cancers, miRNA expression is significantly
      altered, and this has been shown to be a useful diagnostic tool. Several
      computational approaches have been developed for the prediction of miRNA targets.

PMID- 17532530
TI  - Tools for efficient high-throughput synthesis.
AB  - Here, we detail the major developments in methods and techniques that are
      applicable to high-throughput synthesis that have evolved over the past five
      years, with an emphasis on the combination of microwave-based synthesis with
      techniques such as polymer-assisted purification and immobilized reagents and
      catalysts. Other aspects, such as automation, miniaturization and flow-based
      synthesis, are also presented as approaches that can be used for the rapid
      discovery and optimization of small organic molecules.

PMID- 17532531
TI  - Lead discovery by DNA-encoded chemical libraries.
AB  - The isolation of specific binding molecules is a central problem in the drug
      discovery process and might be useful for the elucidation of the biological
      function of proteins identified in genome and proteome research. Libraries of
      organic molecules, conjugated covalently to DNA tags that serve as identification
      bar codes, have been proposed recently as a way to identify ligands of target
      proteins of choice efficiently. Here, we analyze the different strategies for
      constructing DNA-encoded chemical libraries, and the potential and challenges of
      this promising technology.

PMID- 17532532
TI  - Emerging trends in the therapy of COPD: bronchodilators as mono- and combination
      therapies.
AB  - Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disease
      that is characterized by progressive airway obstruction that, unlike asthma, is
      relatively insensitive to bronchodilators and to the classic anti-inflammatory
      therapy, corticosteroids. In this review we consider the potential of
      bronchodilator drugs and corticosteroid drugs that are in clinical development
      for COPD and discuss how the best treatments might be achieved with combinations
      of drugs that are either already launched or close to launch.

PMID- 17532533
TI  - Emerging trends in the therapy of COPD: novel anti-inflammatory agents in
      clinical development.
AB  - During the past ten years, the pharmaceutical industry has focussed on treating
      chronic obstructive pulmonary disease (COPD) as distinct to asthma, and no novel
      anti-inflammatory agents have been launched as therapies for this disease. As our
      understanding of the pathology of COPD has increased it has been established that
      the progressive pulmonary inflammation that is associated with COPD relates to
      disease severity. Thus, it is anticipated that drugs that reduce pulmonary
      inflammation will provide effective, disease-modifying therapies. Here, we
      consider the potential of anti-inflammatory drugs that are currently in clinical
      development for COPD and discuss how these might reduce pulmonary inflammation in
      this disease.

PMID- 17532534
TI  - New developments in synthetic peroxidic drugs as artemisinin mimics.
AB  - The present review describes the current status of synthetic cyclic peroxides,
      trioxanes and trioxolanes that show significant promise as antimalarial drugs
      because of their artemisinin-like activity. The literature from 1996 onwards is
      critically surveyed to provide an update on how an age-old, persistent,
      debilitating and frequently deadly disease could be treated by new, affordable
      and effective medicines possessing the peroxide pharmacophore. The review is not
      exhaustive and does not cover recent progress on the lead structure artemisinin
      and its derivatives. Nevertheless, some mechanistic aspects gleaned from
      artemisinin that have relevance to synthetic peroxides are discussed.

PMID- 17532537
TI  - Dual digital video-autofluorescence imaging for detection of pre-neoplastic
      lesions.
AB  - AIM: The incorporation of autofluorescence (AF) to white light bronchoscopy has
      led to improved sensitivity for the detection of pre-neoplastic lesions in the
      airways. However, AF has difficulty distinguishing benign epithelial changes such
      as bronchitis, previous biopsy, and airway fibrosis from pre-invasive lesions,
      which necessitates extensive biopsy. This frequently results in longer procedural
      time and need for additional sedation that may compromise patient safety,
      increase the risk of bronchospasm, and bleeding from multiple endobronchial
      biopsies. We postulate that dual imaging with simultaneous video and AF
      bronchoscopy of the tracheobronchial tree could improve the low specificity
      observed with AF in the detection of pre-invasive lesions, leading to targeted
      biopsy, good correlation with pathological diagnosis and shorter procedural time.
      METHODS: Forty-eight patients with known or suspected of lung cancer underwent
      video and AF bronchoscopy, which were provided as real-time dual images with SAFE
      3000 (Pentax, Tokyo) between March and August 2006. Biopsy specimens were taken
      from all suspicious areas with two random specimens from normal areas. Values
      were expressed as median and range, and p<0.05 was considered statistically
      significant. RESULTS: Twenty-five suspicious sites were detected by dual imaging
      bronchoscopy, and 126 endobronchial biopsies were evaluated, of which 22 (17.5%)
      were graded as moderate dysplasia and worse. Sensitivity and specificity of dual
      imaging for the detection of high-grade dysplasia were 86% and 94%, respectively,
      with good correlation between bronchoscopic assessment and pathology (r=0.77,
      p<0.0001). However, there were three random biopsy specimens obtained from normal
      or abnormal sites that showed severe dysplasia in two and moderate dysplasia in
      one. Median time taken for airway examination was 4 min (range, 4-4.8), and 5 min
      (range, 4-5) for biopsy, giving a total procedural time of 9 min (range, 8-10).
      There were no procedure-related complications noted. CONCLUSION: Dual imaging
      that allows simultaneous real-time assessment of the lesion with video and AF
      bronchoscopy not only achieves satisfactory sensitivity for the detection of pre
      neoplastic lesions, importantly it improves specificity by allowing targeted
      biopsy, which has led to a marked decrease in procedural time and better patient
      safety.

PMID- 17532538
TI  - A virtual bronchoscopic navigation system under X-ray fluoroscopy for
      transbronchial diagnosis of small peripheral pulmonary lesions.
AB  - We had reported the utility of virtual bronchoscopic navigation system under CT
      guidance for the diagnosis of small peripheral pulmonary lesions (PPLs). This
      study investigated the efficacy of virtual bronchoscopic navigation system for
      the diagnosis of small PPLs under X-ray fluoroscopy. We performed bronchoscopy
      with this system for 94 consecutive patients with 96 PPLs (< or =30mm in longest
      diameter; mean longest diameter, 16.2mm). A standard bronchoscope was used in 38
      cases, and an ultrathin bronchoscope in 58 cases. Virtual bronchoscopic images
      were reconstructed from helical CT data. All the examinations were performed
      under X-ray fluoroscopy with virtual bronchoscopic navigation system, we referred
      both virtual bronchoscopic images and actual bronchoscopic images simultaneously
      to navigate the bronchoscopic pathway to the PPLs. Specimens for pathological
      examination were collected by transbronchial biopsy (TBB) and/or brushing.
      Virtual images accorded well with actual bronchoscopic images. The average total
      examination time was 24.1+/-7.4min (mean+/-S.D.). The overall diagnostic yields
      were 62.5% (60 of 96 PPLs), 71.1% (27 of 38 PPLs) with the standard bronchoscope,
      and 56.9% (33 of 58 PPLs) with the ultrathin bronchoscope. Diagnostic rates were
      35%, 61.4% and 94.7% for lesions < or =10, 10-20, and >20mm, respectively. There
      were eight ground glass opacity (GGO) lesions confirmed only on CT scans; seven
      cases were pathologically diagnosed. All the examinations were performed safely
      with no complications. Bronchoscopy with virtual bronchoscopic navigation under X
      ray fluoroscopy is useful for the diagnosis of small PPLs.

PMID- 17532539
TI  - The area composita of adhering junctions connecting heart muscle cells of
      vertebrates - IV: coalescence and amalgamation of desmosomal and adhaerens
      junction components - late processes in mammalian heart development.
AB  - In the adult mammalian heart, the cardiomyocytes and thus their terminally
      anchored myofibrillar bundles are connected by large arrays of closely spaced or
      even fused adhering junctions (AJs), termed "intercalated disks" (IDs). In recent
      years, the ID complex has attracted special attention as it has become clear that
      several human hereditary cardiomyopathies are caused by mutations of genes
      encoding ID marker proteins, in particular some that are also known as
      constituents of epithelial desmosomes. Previously, we have shown that in the
      mature myocardial ID the compositional differences between desmosome-like and
      adhaerens junctions are, by and large, lost and a composite hybrid structure, the
      area composita, is formed. We now report results from immunofluorescence and
      (immuno-)electron microscopic studies of heart formation during mouse
      embryogenesis and postnatal growth and show that the formation of the IDs with
      extended area composita structures is a late, primarily postnatal process. While
      up to birth small distinct desmosomes and AJs are resolved as predominant ID
      structures, areae compositae of increasing sizes and merged marker protein
      patterns occupy most of the IDs in the mature heart. Differences in the patterns
      of ID formation and amalgamation of the two ensembles of junction proteins in
      time and space are also demonstrated. Together with corresponding observations
      during rat and human heart development our results indicate that ID topogenesis
      and area composita formation are also late developmental processes in other
      mammals. We discuss the importance of the ID and the areae compositae in cardiac
      functions and, consequently, in cardiomyopathies and possible myocardial
      regeneration processes.

PMID- 17532540
TI  - Excess tyrosine rescues the reduced activity of proliferation and differentiation
      of cultured recessive yellow melanocytes derived from neonatal mouse epidermis.
AB  - The murine recessive yellow (Mc1r(e)) is a loss-of-function mutation in the
      receptor for alpha-melanocyte-stimulating hormone, melanocortin receptor 1 (Mc1r)
      and produces yellow coats by inducing pheomelanin synthesis in hair follicular
      melanocytes. However, it is not known whether the Mc1r(e) mutation affects the
      proliferation and differentiation of melanocytes. In this study, the
      proliferation and differentiation of recessive yellow epidermal melanocytes
      cultured in dibutyryl cyclic AMP-supplemented serum-free medium were investigated
      in detail. The melanocytes produced mainly eumelanin in this culture system. The
      proliferation of recessive yellow melanocytes was decreased compared with that of
      wild-type at the e-locus, black melanocytes. The differentiation of melanocytes
      was also delayed and inhibited in recessive yellow mice. Tyrosinase (TYR)
      activity and TYR-related protein 1 (TRP1) and TRP2 (dopachrome tautomerase, DCT)
      expressions were decreased and, in addition, the maturation of stage IV
      melanosomes was inhibited. Excess l-tyrosine (l-Tyr) added to the culture media
      rescued the reduced activity of proliferation of melanocytes. l-Tyr also
      stimulated TYR activity and TRP1 and TRP2 expressions as well as the maturation
      of stage IV melanosomes and pigmentation. These results suggest that the Mc1r(e)
      mutation affects the proliferation and differentiation of melanocytes and l-Tyr
      rescues the reduced proliferative and differentiative activities by stimulating
      TYR activity and TRP1 and TRP2 expressions as well as melanosome maturation.

PMID- 17532541
TI  - Procathepsin D secreted by HaCaT keratinocyte cells - A novel regulator of
      keratinocyte growth.
AB  - Procathepsin D (pCD), the precursor form of lysosomal aspartic protease, is
      overexpressed and secreted by various carcinomas. The fact that secreted pCD
      plays an essential role in progression of cancer has been established. In this
      study, we describe substantial secretion of pCD by the human keratinocyte cell
      line HaCaT, under serum-free conditions. Moreover, exogenous addition of purified
      pCD enhanced the proliferation of HaCaT cells. The proliferative effect of pCD
      was inhibited by a monoclonal antibody against the activation peptide (AP) of
      pCD. Treatment of HaCaT cells with pCD or AP led to the secretion of a set of
      cytokines that might promote the growth of cells in a paracrine manner. The role
      of secreted pCD and its mechanism of action were studied in a scratch wound model
      and the presence of pCD and AP enhanced regeneration, while this effect was
      reversed by the addition of anti-AP antibody. Expression and secretion of pCD was
      upregulated in HaCaT cells exposed to various stress conditions. Taken together,
      our results strongly suggest that the secretion of pCD is not only linked to
      cancer cells but also plays a role in normal physiological conditions like wound
      healing and tissue remodeling.

PMID- 17532542
TI  - Role of transcription factors in mediating post-ischemic cerebral inflammation
      and brain damage.
AB  - Inflammation is a known precipitator of neuronal death after cerebral ischemia.
      The mechanisms that promote or curtail the start and spread of inflammation in
      brain are still being debated. By virtue of their capability to modulate gene
      expression, several transcription factors induced in the ischemic brain can
      modulate the post-ischemic inflammation. While the induction of transcription
      factors such as IRF1, NF-kappaB, ATF-2, STAT3, Egr1 and C/EBPbeta is thought to
      promote post-ischemic inflammation, activation of transcription factors such as
      HIF-1, CREB, c-fos, PPARalpha, PPARgamma and p53 is thought to prevent post
      ischemic inflammation and neuronal damage. Of these, PPARgamma which is a ligand
      activated transcription factor was recently shown to prevent inflammatory gene
      expression in several animal models CNS disorders. This review article discusses
      some of the molecular mechanisms of PPARgamma induction by its agonists following
      focal cerebral ischemia.

PMID- 17532543
TI  - Synthesis, characterization and biological activity of Schiff base analogues of
      indole-3-carboxaldehyde.
AB  - Eight novel heterocyclic Schiff bases derived from the condensation reactions of
      indole 3-carboxaldehyde with different l-amino acids (histidine, glutamic acid,
      aspartic acid, leucine, valine) as well as with some aminophenols, have been
      synthesized and characterized by various spectroscopic methods (IR, MS, (1)H
      NMR). Schiff base derivatives of indole 3-carboxaldehyde were labeled with
      (99m)Tc and radiochemical purity was above 97% which is ascertained by instant
      thin layer chromatography using different solvent conditions. Stability studies
      of all the derivatives of indole 3-carboxaldehyde was determined under
      physiological conditions and were stable for more than 24h. Blood clearance
      showed a quick wash out from the circulation and biological half life was found
      to be t((1/2))(F)=1h 15min; t((1/2))(S)=10h 05min. Excellent quality radioimages
      of tumor bearing mice were recorded showing rapid clearance of background
      activity, visualization of tumor at 3h and clearance from kidneys of histidine
      analogue which was further evidenced in biodistribution studies. Antimicrobial
      activity of these Schiff base compounds was evaluated against Bacillus subtilis,
      Pseudomonas fluorescence, Staphylococcus aureus, Aspergillus niger, Candida
      albicans and Trichophyton rubrum.

PMID- 17532544
TI  - Synthesis and biological evaluation of some thiazolyl and thiadiazolyl
      derivatives of 1H-pyrazole as anti-inflammatory antimicrobial agents.
AB  - Four series of pyrazolyl benzenesulfonamide derivatives have been synthesized.
      The first series was prepared by cyclization of the intermediate N,N
      dimethylaminomethylene-4[3-phenyl-4-(substituted thiosemicarbamoyl
      hydrazonomethyl)-1H-pyrazol-1-yl]benzenesulfonamide 2a-c with ethyl bromoacetate
      to afford the corresponding thiazolidinyl derivatives 3a-c. The second series was
      prepared by cyclization of the key intermediates 2a-c with 4-bromophenacyl
      bromide giving rise to thiazolinyl derivatives 4a-c. Thiadiazolyl derivatives 5a
      c were obtained by heating 2a-c with 2M FeCl(3) solution. Refluxing the
      intermediates 2a-c in acetic anhydride yielded the corresponding thiadiazolinyl
      derivatives 6a-c. All the target compounds showed anti-inflammatory activity and
      three of them 3b, 3c and 4c surpassed that of indomethacin both locally and
      systemically in the cotton pellet granuloma and rat paw edema bioassay. The
      active compounds showed selective inhibitory activity towards COX-2 enzyme as
      revealed by the in vitro enzymatic assay. All the tested compounds proved to have
      superior gastrointestinal (GI) safety profiles as compared to indomethacin, when
      tested for their ulcerogenic effects. The acute toxicity study of compounds
      having promising anti-inflammatory activity (3b, 3c and 4c) indicated that they
      are well tolerated both orally and parenterally. Antimicrobial activity tests
      expressed as minimal inhibitory concentrations (MIC), revealed that compounds 3b
      and 4a showed comparable antibacterial activity to that of ampicillin against
      Escherichia coli, while compounds 3a, 3c and 4a possessed about half the activity
      of ampicillin against Staphylococcus aureus. On the other hand, the results
      showed that all the tested compounds have weak or no antifungal activity against
      Candida albicans except for compounds 6b and 6c that showed half the activity of
      the control antifungal drug used (clotrimazole).

PMID- 17532545
TI  - Synthesis and anti-platelet activity of novel arylsulfonate--acylhydrazone
      derivatives, designed as antithrombotic candidates.
AB  - In this work, we describe a new class of promising anti-platelet drug candidates
      with significant antithrombotic activity in vivo. This new series of compounds
      was structurally planned by modification of known thrombin inhibitors based on
      the use of acylhydrazone subunit, as a nonpeptide scaffold, and variations at P1
      moiety. Three different families of arylsulfonate-acylhydrazone derivatives were
      designed. The bioassays indicated the first class of derivatives represented by
      4f (LASSBio-693) and 4j (LASSBio-743), which were active in inhibiting the
      platelet aggregation induced by thrombin. The second class represented by
      compounds 4e (LASSBio-774) and 4h (LASSBio-480) that selectively inhibit the
      platelet aggregation involving TXA(2) formation. Finally, the third class of
      derivatives was identified acting as a novel symbiotic agent able to inhibit the
      platelet aggregation induced by collagen or AA and by thrombin, represented by
      compounds 4b (LASSBio-694) and 4g (LASSBio-770).

PMID- 17532546
TI  - Lack of protection of mice against Staphylococcus aureus despite a significant
      immune response to immunization with a DNA vaccine encoding collagen-binding
      protein.
AB  - Collagen-binding protein (CNA) is the major Staphylococcus aureus adhesin
      responsible for high affinity binding to collagen and is assumed to be a major
      virulence factor in infection and disease. Mutants lacking the cna gene are less
      virulent than the parent strain in models of septic arthritis, osteomyelitis,
      keratinitis, and endocarditis. In order to investigate the immunological and
      protective properties of a CNA-based DNA vaccine, a eukaryotic expression vector
      pCNA was constructed which expressed the collagen-binding domain of this adhesin
      in transfected cells. Three groups of 11 Balb/c mice received three injection of
      either pCNA, the empty expression vector (pCI) or PBS. Those injected with pCNA
      showed hi titre (64000) antibody and evidence of a cell-mediated immune response
      (CMI). The anti-CNA antibodies recognized the intact bacteria and prevented
      binding to collagen in vitro. However, the vaccination did not protect against
      bacterial challenge using the intra-peritoneal route of infection. Moreover, S.
      aureus that had been treated with sera from vaccinated mice caused a more severe
      infection than bacteria treated with sera from non-vaccinated mice. In summary,
      DNA vaccination against CNA produced a strong antibody and cellular response in
      mice but failed to protect from i.p. infection by S. aureus.

PMID- 17532547
TI  - Eczema vaccinatum as an adverse event following exposure to vaccinia virus: case
      definition & guidelines of data collection, analysis, and presentation of
      immunization safety data.

PMID- 17532548
TI  - Cholinesterase activity in Gammarus pulex (Crustacea Amphipoda): characterization
      and effects of chlorpyrifos.
AB  - The aim of this study was to characterize cholinesterase (ChE) activity in
      Gammarus pulex, an abundant and ecologically relevant species of the European
      stream environment. Biochemical and pharmacological properties were tested using
      different substrates (acetylthiocholine iodide, propionylthiocholine iodide and
      butyrylthiocholine iodide) and selective inhibitors (eserine sulfate, BW284c51
      and iso-OMPA). In a second part, the in vitro and in vivo effects of a widely
      used organophosphorous pesticide, chlorpyrifos, on ChE activity were
      investigated. The results suggest that G. pulex possess only one ChE which
      displays the typical properties of an acetylcholinesterase, since: (1) it
      hydrolyses to the substrate acetylthiocholine at a higher rate than all other
      tested substrates and (2) it is highly sensitive to eserine sulphate and
      BW284c51, but not to iso-OMPA. In vitro and in vivo inhibitions were observed for
      highly different contamination levels, which suggests that bioaccumulation and
      biotransformation mechanisms are involved. In vivo AChE inhibition was observed
      at realistic environmental concentrations, with lethal effects appearing at
      inhibitions higher than 50%. The results of this study show the value of G. pulex
      as a sentinel organism for environmental assessment.

PMID- 17532549
TI  - Activation of TRPC6 calcium channels by diacylglycerol (DAG)-containing
      arachidonic acid: a comparative study with DAG-containing docosahexaenoic acid.
AB  - We synthesized a diacylglycerol (DAG)-containing arachidonic acid, i.e., 1
      stearoyl-2-arachidonyl-sn-glycerol (SAG), and studied its implication in the
      modulation of canonical transient receptor potential sub-type 6 (TRPC6) channels
      in stably-transfected HEK-293 cells. SAG induced the influx of Ca(2+), and also
      of other bivalent cations like Ba(2+) and Sr(2+), in these cells. SAG-evoked
      Ca(2+) influx was not due to its metabolites as inhibitors of DAG-lipase
      (RHC80267) and DAG-kinase (R50922) failed to inhibit the response of the same. To
      emphasise that SAG exerts its action via its DAG configuration, but not due to
      the presence of stearic acid at sn-1 position, we synthesized 1-palmitoyl-2
      arachidonyl-sn-glycerol (PAG). PAG-induced increases in [Ca(2+)](i) were not
      significantly different from those induced by SAG. For the comparative studies,
      we also synthesized the DAG-containing docosahexaenoic acid, i.e., 1-stearoyl-2
      docosahexaenoyl-sn-glycerol (SDG). We observed that SDG and 1,2-dioctanoyl-sn
      glycerol (DOG), a DAG analogue, also evoked increases in [Ca(2+)](i), which were
      lesser than those evoked by SAG. However, activation of TRPC6 channels by all the
      DAG molecular species (SAG, DOG and SDG) required Src kinases as the tyrosine
      kinase inhibitors, PP2 and SU6656, significantly attenuated the increases in
      [Ca(2+)](i) evoked by these agents. Moreover, disruption of lipid rafts with
      methyl-beta-cyclodextrin completely abolished SAG-, DOG- and SDG-induced
      increases in [Ca(2+)](i). The present study shows that SAG as well as SDG and DOG
      stimulate Ca(2+) influx through the activation of TRPC6 calcium channels which
      are regulated by Src kinases and intact lipid raft domains.

PMID- 17532550
TI  - Interferon-alpha and cancer: mechanisms of action and new perspectives of
      clinical use.
AB  - Interferons-alpha (IFN-alpha) are pleiotropic cytokines belonging to type I IFNs,
      extensively used in the treatment of patients with some types of cancer and viral
      disease. IFN-alpha can affect tumor cell functions by multiple mechanisms. In
      addition, these cytokines can promote the differentiation and activity of host
      immune cells. Early studies in mouse tumor models showed the importance of host
      immune mechanisms in the generation of a long-lasting antitumor response after
      treatment of the animals with IFN-alpha/beta. Subsequently, an ensemble of
      studies based on the use of genetically modified tumor cells expressing specific
      IFN molecules provided important information on the host-mediated antitumor
      mechanisms induced by the local production of IFN-alpha. Of note, several studies
      have then underscored new immunomodulatory effects of IFN-alpha, including
      activities on T cells and dendritic cells, which may lead to IFN-induced
      antitumor immunity. In addition, recent reports on new immune correlates in
      cancer patients responding to IFN-alpha represent additional evidence on the
      importance of the interactions of IFN-alpha with the immune system for the
      generation of a durable antitumor response. On the whole, this knowledge suggests
      the advantage of using these cytokines as adjuvants of cancer vaccines and for
      the in vitro generation of highly active dendritic cells to be utilized for
      therapeutic vaccination of cancer patients.

PMID- 17532551
TI  - Development of sensitive chemical and immunochemical methods for detecting
      sulfated sialic acids and their application to glycoconjugates from sea urchin
      sperm and eggs.
AB  - Sulfated sialic acid (SiaS) is a unique sialic acid (Sia) derivative in which an
      additional anionic group is attached to a carboxylated monosaccharide. Very
      little is known about the occurrence and biologic function of SiaS, due to the
      limitations of analytical methods to detect it in minute amounts. In this study,
      to develop methods and probes for detecting and pursuing the functions of SiaS,
      we developed sensitive chemical and immunochemical detection methods. First, we
      synthesized as model compounds 4-methylumbelliferyl glycosides of 8-O- and 9-O
      sulfated Sia consisting of N-acetylneuraminic acid (Neu5Ac), N-glycolylneuraminic
      acid (Neu5Gc), and deaminoneuraminic acid (Kdn). Second, we applied fluorometric
      high performance liquid chromatography (HPLC) analysis to these synthetic
      glycosides. After acid hydrolysis of the samples, the liberated SiaS were labeled
      with a fluorescent reagent, 1,2-diamino-4,5-methylenedioxybenzene, and analyzed
      on fluorometric HPLC. We established an optimal elution condition for successful
      separation of 8-O- and 9-O-sulfated Neu5Ac, Neu5Gc, and Kdn on HPLC. Third, we
      generated a monoclonal antibody (mAb) 2C4 against SiaS using sea urchin egg
      components as the immunogen. mAb.2C4 recognizes both 8-O-sulfated Neu5Ac
      (Neu5Ac8S) and Neu5Gc8S, whereas the previously prepared mAb.3G9 only recognizes
      Neu5Ac8S. Finally, using the fluorometric HPLC and monoclonal antibodies, we
      demonstrated that glycoconjugates from sea urchin sperm exclusively contained
      Neu5Ac8S, whereas those from eggs contained Neu5Gc8S. Furthermore, we clarified
      the quantitative differences in the SiaS content in eggs and sperm from two
      different species of sea urchins. Immunostaining using mAb.2C4 showed that
      Neu5Gc8S is localized in the cortical granules in unfertilized eggs, whereas it
      is localized in the outer surface of the fertilization layer as well as in the
      inner surface of fertilized eggs. Thus, 8-O-sulfation is dependent on the
      species, gametic cell-type, site-localization of the eggs, and glycoconjugates.

PMID- 17532552
TI  - Molecular dynamics simulations of pea (Pisum sativum) lectin structure with octyl
      glucoside detergents: the ligand interactions and dynamics.
AB  - The mitogenic pea (Pisum sativum) lectin is a legume protein of non
      immunoglobulin nature capable of specific recognition of glucose derivatives
      without altering its structure. Molecular dynamics simulations were performed in
      a realistic environment to investigate the structure and interaction properties
      of pea lectin with various concentrations of n-octyl-beta-d-glucopyranoside (OG)
      detergent monomers distributed inside explicit solvent cell. In addition, the
      diffusion coefficients of the ligands (OG, Ca2+, Mn2+, and Cl-) and the water
      molecules were also reported. The structural flexibility of the lectin was
      conserved in all simulations. The self-assembly of OG monomers into a small
      micelle at the hydrophobic site of the lectin was noticed in the simulation with
      20 OG monomers. The interaction energy analysis concludes that the lectin was
      appropriately termed an adaptive structure. One or rarely two binding sites were
      observed at an instant in each simulation that were electrostatically favoured
      for the OG to interact with the surface amino acid residues. Enhanced binding of
      OG to the pea lectin was quantified in the system containing only Ca2+ divalent
      ions. Interestingly, no binding was observed in the simulation without divalent
      ions. Furthermore, the lectin-ligand complex was stabilized by multiple hydrogen
      bonds and at least one water bridge. Finally, the work was also in accordance
      with the published work elsewhere that the simulations performed with different
      initial conditions and using higher nonbonded cutoffs for the van der Waals and
      electrostatic interactions provide more accurate information and clues than the
      single large simulation of the biomolecular system of interest.

PMID- 17532553
TI  - Effects of lithium on the human erythrocyte membrane and molecular models.
AB  - The mechanism whereby lithium carbonate controls manic episodes and possibly
      influences affective disorders is not yet known. There is evidence, however, that
      lithium alters sodium transport and may interfere with ion exchange mechanisms
      and nerve conduction. For these reasons it was thought of interest to study its
      perturbing effects upon membrane structures. The effects of lithium carbonate
      (Li+) on the human erythrocyte membrane and molecular models have been
      investigated. The molecular models consisted in bilayers of
      dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidylethanolamine
      (DMPE), representing classes of phospholipids located in the outer and inner
      monolayers of the erythrocyte membrane, respectively. This report presents the
      following evidence that Li+ interacts with cell membranes: a) X-ray diffraction
      indicated that Li+ induced structural perturbation of the polar head group and of
      the hydrophobic acyl regions of DMPC and DMPE; b) experiments performed on DMPC
      large unilamellar vesicles (LUV) by fluorescence spectroscopy also showed that
      Li+ interacted with the lipid polar groups and hydrophobic acyl chains, and c) in
      scanning electron microscopy (SEM) studies on intact human erythrocytes the
      formation of echinocytes was observed, effect that might be due to the insertion
      of Li+ in the outer monolayer of the red cell membrane.

PMID- 17532554
TI  - Functional and histological changes after myoblast injections in the porcine
      rhabdosphincter.
AB  - OBJECTIVE: Transurethral ultrasound-guided injection of autologous myoblasts has
      recently been shown to cure urinary stress incontinence. In the present study,
      the dose-dependent changes in maximal urethral closure pressures after
      application of myoblasts were investigated in a porcine animal model. METHODS:
      Myoblast cultures were grown from a porcine muscle biopsy. The biopsy was
      enzymatically dissociated by using a modified cell dispersion technique. Single
      myoblasts in suspension were manually collected with a micropipette under
      microscopic control. Next a clonal myoblast culture was prepared. Before the
      cells were applied, fluorescence labelling (PKH) was used to assess integration
      of the injected myoblasts into the rhabdosphincter. With the help of a
      transurethral ultrasound probe (23 F, 11 MHz) and a special injection system, the
      myoblasts were injected into the rhabdosphincter of five pigs under direct
      sonographic control. Into two different areas of the rhabdosphincter, increasing
      different cell counts were injected (total volume 1.5 ml). At each area, 10
      depots of 150 microl volume were injected all along the rhabdosphincter. The
      following cell counts were used: 1.5 x 10(6), 2.1 x 10(6), 4.2 x 10(6) (low
      range) 5.69 x 10(6), 8.1 x 10(6), 1.13 x 10(7), 1.6 x 10(7) (mid range) 2.26 x
      10(7), 4.4 x 10(7), and 7.8 x 10(7) (high range). To avoid possible cell
      rejection, we immunosuppressed the pigs with daily cortisone (1g Solu Dacortin)
      because allogenic myoblasts were used. Urethral pressure profiles (UPPs) were
      measured before and 3 wk postoperatively before the pigs were put to sleep. The
      lower urinary tract was removed in all pigs for histological analysis. RESULTS:
      Histological examination of the specimens revealed that the injected cells had
      survived at the injection site and had formed new myofibres. Overall the UPP
      curves revealed dose-dependent changes. Statistically significant increased
      pressure values of up to more than 300% could be observed in all cases in which
      higher concentrations of cells had been applied. Increases were also noted in mid
      range concentrations although not to such a high extent (approximately 150%).
      Pressure values had even diminished (approximately 50%) after injecting the three
      lowest concentrations (1.5 x 10(6), 2.1 x 10(6), 4.2 x 10(6)). CONCLUSIONS: The
      present results show that the effects after application of myoblasts into the
      rhabdosphincter are dose-dependent.

PMID- 17532555
TI  - Exposure of adult rats to estradiol valerate induces ovarian cyst with early
      senescence of follicles.
AB  - Environmental and therapeutic estrogens are known to play an important role in
      modulating the reproductive life and pubertal maturation in males as well as in
      females. Animal studies have shown that exogenously administered estrogen induces
      follicular cysts. However, the probable mechanisms underlying this abnormal
      ovarian development and its impact on steroidogenesis have been ill defined. The
      present study was therefore carried out to understand the ontogeny of ovarian
      pathology owing to adult estrogenisation. Regularly cycling female Holtzman rats
      were sacrificed at one week, two weeks, three weeks and four weeks after a
      subcutaneous administration of 2 mg of estradiol valerate (E(2)V). The effect of
      this supra-physiological estrogen on serum endocrine profiles, development of
      follicular cysts, follicular apoptosis and expression of markers of
      folliculogenesis viz., estrogen receptor (ER)-beta, inhibin A and progesterone
      receptor (PR) were studied. Results indicate a temporal augmentation of
      steroidogenesis, which was associated with induction of follicular cyst with
      theca cell hyperplasia and induction of apoptosis in the primary and secondary
      follicles of the ovaries. Immuno-histochemical localization showed an increase in
      inhibin A with a reduction in ER-beta and PR indicating early maturation, poor
      follicle growth and granulosa cell differentiation. Results indicate that
      exposure to exogenous estrogen in adulthood can have deleterious effects on the
      ovarian physiology and endocrinology which may ultimately lead to cystogenesis,
      loss of follicle pool and early senescence.

PMID- 17532556
TI  - Management of ACTH-secreting supradiaphragmatic adenomas.
AB  - Supradiaphragmatic adrenocorticotropic hormone (ACTH) secreting pituitary
      adenomas are exceptionally encountered (14 cases previously described) and raise
      issues concerning their nosology and management. If surgery is the treatment of
      choice, the nature of surgical approach (craniotomy, transsphenoidal approach)
      remains controversial. To illustrate this issue, we presented two cases of
      supradiaphragmatic ACTH secreting pituitary adenomas successfully excised via a
      subfrontal approach. Both patients were female (20 and 41 years) and had a
      typical Cushing's syndrome. MRI revealed, in both cases, a suprasellar mass in
      contact with the pars tuberalis of the pituitary. In the first case, the patient
      underwent initially a transsphenoidal approach with negative exploration and
      subsequent partial hypophysectomy. One year later, the patient was operated on
      again via a subfrontal approach, allowing excision of a supradiaphragmatic
      adenoma and a complete cure of Cushing's disease. In the second case, the patient
      underwent initially a subfrontal approach and was definitely cured. In both
      cases, the diaphragma sellae was found to be intact and the pituitary stalk could
      be preserved. Postoperative MRI demonstrated a clearly visible intact pituitary
      stalk in conjunction with normal aspect of the pituitary. Supradiaphragmatic
      pituitary adenomas are most likely adenomas of the pituitary stalk with extra
      axial development. Surgery remains the treatment of choice. Should the superior
      approach be preferred, the transsphenoidal-transtuberculum sellae approach may
      represent a viable alternative when performed by a well-trained surgical team.
      Surgery may be difficult, and drawbacks are non negligible, particularly in
      elderly patients. In these cases, stereotactic radiosurgery should receive more
      consideration.

PMID- 17532557
TI  - RNA interference-mediated knockdown of DNMT1 and DNMT3B induces CXCL12 expression
      in MCF-7 breast cancer and AsPC1 pancreatic carcinoma cell lines.
AB  - It has been recently demonstrated that in colonic carcinoma, CXCL12 expression
      undergoes epigenetic regulation by methylation of cytosine in cytosine-guanosine
      (CpG) dinucleotides of the promoter sequence. Using lentiviral vectors, we
      generated stable RNA interference-mediated knockdown of DNMT1 and DNMT3B in MCF-7
      breast cancer and AsPC1 pancreatic carcinoma cell lines. Employing reverse
      transcription real-time quantitative PCR and immunofluorescence analysis, we
      determined re-expression levels of CXCL12 transcript and protein in these cells.
      Bisulfite sequencing revealed that the level of promoter demethylation appeared
      more effective in cells expressing DNMT1 siRNA than in those expressing DNMT3B
      siRNA, and this correlated with higher expression of CXCL12. Moreover, the
      combined expression of DNMT1 and DNMT3B siRNAs enhanced promoter demethylation
      that was associated only with a slight increase of CXCL12 expression. However,
      the demethylating agent 5-Aza-2'-deoxycytidine exhibited the strongest effect on
      promoter demethylation, which correlated with the highest expression level of
      CXCL12 transcript and protein in MCF-7 and AsPC1 cells. Our findings suggest that
      DNMT1 plays a key role in maintenance of methylation, and DNMT3B may act as an
      accessory DNA methyltransferase to epigenetically silence CXCL12 expression in
      MCF-7 and AsPC1 cells.

PMID- 17532558
TI  - Expression and biological role of the prostaglandin D synthase/SOX9 pathway in
      human ovarian cancer cells.
AB  - New therapeutic strategies for ovarian cancer include the identification of
      involved signaling pathways that could potentially serve as a source of
      biomarkers for early stages of the disease. In this study, we show that the
      embryonic male prostaglandin D synthase (Pgds)/SOX9 pathway is expressed at both
      the RNA and protein levels in different types of human ovarian tumors, pointing
      to Pgds and SOX9 as possible diagnostic markers for ovarian carcinomas. Using
      ovarian cancer cell lines, we found, first, that components of the Pgds/SOX9
      pathway are expressed in these cells, and second, that treatment of these cells
      with prostaglandin D2 (PGD2) can inhibit their growth via its DP1 receptor and
      induce apoptosis. Finally, using siRNA and overexpression strategies, we
      demonstrate that SOX9 expression is induced by PDG2 and is responsible for PDG2
      mediated growth inhibition. Accordingly, as stimulating the PGD2/DP1 signal
      transduction pathway upregulates SOX9 expression, either activators of this
      pathway or DP1 agonists may be useful as new therapeutic agents.

PMID- 17532559
TI  - Effective treatment of PAH contaminated Superfund site soil with the peroxy-acid
      process.
AB  - Peroxy-organic acids are formed by the chemical reaction between organic acids
      and hydrogen peroxide. The peroxy-acid process was applied to two Superfund site
      soils provided by the U.S. Environmental Protection Agency (EPA). Initial small
      scale experiments applied ratios of 3:5:7 (v/v/v) or 3:3:9 (v/v/v) hydrogen
      peroxide:acetic acid:deionized (DI) water solution to 5g of Superfund site soil.
      The experiment using 3:5:7 (v/v/v) ratio resulted in an almost complete
      degradation of the 14 EPA regulated polycyclic aromatic hydrocarbons (PAHs) in
      Bedford LT soil during a 24-h reaction period, while the 3:3:9 (v/v/v) ratio
      resulted in no applicable degradation in Bedford LT lot 10 soil over the same
      reaction period. Specific Superfund site soil characteristics (e.g., pH, total
      organic carbon content and particle size distribution) were found to play an
      important role in the availability of the PAHs and the efficiency of the
      transformation during the peroxy-acid process. A scaled-up experiment followed
      treating 150g of Bedford LT lot 10 soil with and without mixing. The scaled-up
      processes applied a 3:3:9 (v/v/v) solution resulting in significant decrease in
      PAH contamination. These findings demonstrate the peroxy-acid process as a viable
      option for the treatment of PAH contaminated soils. Further work is necessary in
      order to elucidate the mechanisms of this process.

PMID- 17532560
TI  - A novel method to enhance polychlorinated dibenzo-p-dioxins and dibenzofurans
      removal by adding bio-solution in EAF dust treatment plant.
AB  - In order to understand the effect of different amounts of powder-activated carbon
      (PAC) injection and bio-solution (NOE-7F) addition on the removal efficiencies of
      polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) in a fly ash
      treatment plant with Waelz rotary kiln process, the PCDD/F concentrations in the
      stack flue gasses were measured and discussed. In the amount of 20, 40 and 50
      kg/h PAC injection, the removal efficiencies of PCDD/Fs in the stack flue gas
      were 86, 96 and 97%, respectively. While adding more amounts of PAC did enhance
      the removal efficiencies, the reduction fractions of low chlorinated PCDD/F
      congeners were much higher than those of highly chlorinated PCDD/F congeners.
      Particularly, a lower amount of PAC injection (20 kg/h), not only cannot remove
      highly chlorinated PCDD/Fs, but also the carbon surface of the PAC can act as a
      precursor for the formation promotion of highly chlorinated PCDD/F congeners. The
      addition of NOE-7F in the raw materials had the dechlorination effect on the
      PCDD/F removal and mainly inhibited highly chlorinated PCDD/F formation. The
      combination of both PAC injection and NOE-7F addition has a high potential for
      practical application.

PMID- 17532561
TI  - Mathematical modeling for the evaluation of zinc removal efficiency on clay
      sorbent.
AB  - The adsorption characteristics of zinc ion from aqueous solution on the lateritic
      clay were investigated through batch and column mode of operation. The system
      variables were optimized to evaluate the maximum extent of zinc adsorption as
      well as for the purpose of modeling. A model equation correlating zinc adsorption
      with input concentration was described. The adsorption behavior can well be
      described by Freundlich isotherm model rather than Langmuir isotherm model. The
      favorable and spontaneous nature of adsorption was indicated from the
      thermodynamical parameters. The capacity was determined from isotherm parameters
      in batch mode and breakthrough parameters in column mode. The bed depth service
      time (BDST) model was utilized to predict column efficiency corresponding to
      different bed heights. Elution performance of retained zinc, using HNO(3) of
      definite composition, was examined from elution profile. Efficiency of the
      process was determined through repetitive operation cycles of retention and
      elution. Effectiveness of the process was judged through estimation of efficiency
      versus the cost of operation.

PMID- 17532562
TI  - Biological phenol removal using immobilized cells in a pulsed plate bioreactor:
      effect of dilution rate and influent phenol concentration.
AB  - The continuous aerobic biodegradation of phenol in synthetic wastewater was
      carried out using Nocardia hydrocarbonoxydans immobilized over glass beads packed
      between the plates in a pulsed plate bioreactor at a frequency of pulsation of
      0.5s(-1) and amplitude of 4.7 cm. The influence of dilution rate and influent
      phenol concentration on start up and steady state performance of the bioreactor
      was studied. The time taken to reach steady state has increased with increase in
      dilution rate and influent phenol concentration. It was found that, as the
      dilution rate is increased, the percentage degradation has decreased. Steady
      state percentage degradation was also reduced with increased influent phenol
      concentration. Almost 100% degradation of 300 and 500 ppm influent phenol could
      be achieved at a dilution rate of 0.4094 h(-1) and more than 99% degradation
      could be achieved with higher dilution rates. At a higher dilution rate of 1.0235
      h(-1) and at concentrations of 800 and 900 ppm the percentage degradation has
      reduced to around 94% and 93%, respectively. The attached biomass dry weight,
      biofilm thickness and biofilm density at steady state were influenced by influent
      phenol concentration and dilution rate.

PMID- 17532563
TI  - Electrokinetic and adsorption properties of sepiolite modified by 3
      aminopropyltriethoxysilane.
AB  - Surface modification of clay minerals has become increasingly important for
      improving the practical applications of clays such as fillers and adsorbents. An
      investigation was carried out on the surface modification of sepiolite with
      aminopropylsilyl groups in 3-aminopropyltriethoxysilane (3-APT). The zeta
      potential of the modified sepiolite suspensions was measured as a function of
      initial electrolyte concentration and equilibrium pH using a Zeta Meter 3.0 for
      modified sepiolite. The utility of the 3-APT-modified sepiolite was investigated
      as an adsorbent for removal of various heavy metal ions such as Fe, Mn, Co, Zn,
      Cu, Cd and Ni from aqueous solutions. The effects of various factors on the
      adsorption, such as pH, ionic strength and temperature of the solution were
      studied. The results showed that the amount adsorbed increases with solution pH
      in the pH range of 1.5 and 7.0; indicated that the modified sepiolite adsorbed Fe
      and Mn ions more than other metal ions such as Co, Zn, Cu, Cd and Ni. It was
      found that the temperature had an important effect on metal ion adsorption by the
      modified sepiolite. The adsorption isotherm has been determined and data have
      been analyzed according to the Langmuir and Freundlich models.

PMID- 17532564
TI  - Proceedings of the 1st European Conference on Environmental Applications of
      Advanced Oxidation Processes. September 7-9, 2006. Chania, Greece.

PMID- 17532565
TI  - Novel inorganic ion exchange materials based on silicates; synthesis, structure
      and analytical applications of magneso-silicate and magnesium alumino-silicate
      sorbents.
AB  - Two novel inorganic ion exchange materials magneso-silicate and magnesium alumino
      silicate have been synthesized under identical conditions. The structure of these
      materials was established by chemical analysis, X-ray diffraction,
      thermogravemetric and differential thermal analyses, Fourier transform infrared
      spectroscopy and X-ray fluorescence analysis. Magneso-silicate and magnesium
      alumino-silicate were found to have the formulas MgSi(5.59)O(12.18).5.93H(2)O and
      MgAl(2.32)Si(5.2)O(14.88).18.23H(2)O, respectively. The structure of both
      sorbents was arranged and predict according to the ChemDraw Ultra program. The
      ion exchange capacities of these materials for some radionuclides and heavy
      metals Cs(+), Co(2+), Cd(2+), Zn(2+) and Cu(2+) were investigated and the data
      obtained showed that magnesium alumino-silicate has a higher capacity for these
      cations compared to magneso-silicate. Distribution coefficients in nitric acid
      medium have been evaluated to explore the separation potentiality of magneso
      silicate and magnesium alumino-silicate for Cs(+), Co(2+), Cd(2+), Cu(2+), Zn(2+)
      and Fe(3+) ions. Sorption isotherms for all cations were investigated and the
      data showed the applicability of Freundlich isotherm for all cases.

PMID- 17532566
TI  - WITHDRAWN: Simple and rapid spectrophotometric method for the determination of
      bendiocarb in its formulations and environmental samples.
AB  - This article has been withdrawn consistent with Elsevier Policy on Article
      Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). The Publisher
      apologizes for any inconvenience this may cause.

PMID- 17532567
TI  - Integrated photochemical and biological treatment of a commercial textile
      surfactant: process optimization, process kinetics and COD fractionation.
AB  - The biodegradability of surfactants is a frequent and complex issue arising both
      at domestic as well as industrial treatment facilities. In the present
      experimental study, the integrated photochemical (H(2)O(2)/UV-C) and biochemical
      (activated sludge) treatment of a commercial grade nonionic/anionic textile
      surfactant formulation was investigated. Photochemical baseline experiments have
      shown that once the initial pH and H(2)O(2) dose were optimized, practically
      complete COD removal (COD(o)=500+/-30mgL(-1)) could be achieved. Once the COD was
      elevated to values being typical for the textile fabric preparation stage,
      treatment efficiency was seriously retarded provided that the photochemical
      treatment conditions remained constant. Moreover, a definite relationship existed
      between H(2)O(2) consumption and COD removal for H(2)O(2)/UV-C advanced oxidation
      of the textile surfactant. In the second part of the study, COD abatement was
      modeled for the biodegradation of untreated and photochemically pretreated
      textile surfactant formulation according to their COD fractions. Results have
      indicated that the readily biodegradable and rapidly hydrolysable COD fractions
      of the textile surfactant solution could be appreciably increased upon exposure
      to an optimum H(2)O(2) concentration (60mM; i.e. 2.1g H(2)O(2) (g COD(o))(-1))
      and extended UV-C irradiation times (i.e. 90 and 120min).

PMID- 17532568
TI  - Photosensitized oxidation by dioxygen as the base for drinking water
      disinfection.
AB  - Efficiencies of the series water-soluble anionic and cationic sensitizers have
      been studied in photodynamic natural water disinfection. It was found that only
      cationic sensitizers are efficient in photooxidative bacteria killing during
      photodynamic water treatment. The difference in photodynamic action towards
      different groups of microorganisms has been observed. The most vulnerable are
      enterococcus and enterococcus faecalis. Spores of sulfite-reducing clostridium
      are resistant to photodynamic action but, to provide drinking water, clostridium
      may be removed by sedimentation and filtration. The dependence of
      photodisinfection on treatment conditions was studied. It was found that sunlight
      along with artificial visible light sources may be used for photodynamic water
      treatment. The photodynamic step, arranged with artificial visible light source,
      was included in a process of conventional water purification instead of chlorine
      disinfection. Preliminary pilot testing have shown that photodynamic water
      disinfection in combination with coagulation, sedimentation, sand and carbon
      filtrations (latter-to remove sensitizer and products of its photolysis) provides
      water of high quality, free of bacteria and chemicals as well.

PMID- 17532569
TI  - In vitro effects of adrenomedullin and calcitonin gene related peptide on the
      release of serotonin and amino acids from rat dorsal spinal cord.
AB  - Adrenomedullin (AM) and calcitonin gene-related peptide (CGRP) are structurally
      related, interact with each others receptors and show overlapping biological
      activities. Immunoreactivity (IR) and mRNAs along with binding sites for both
      CGRP and adrenomedullin have been shown in the rat spinal cord. CGRP mediates the
      transmission of nociceptive information at the spinal cord level and both
      peptides has shown to induces c-fos expression and accumulation of cAMP in spinal
      cells. In this study, HPLC methods were used to investigate the effects of AM and
      CGRP on the basal and K+-evoked release of serotonin, glutamate (Glu), aspartate
      (Asp), glycine (Gly) and gamma amino butyric acid (GABA) from the slices prepared
      from the rat spinal cord. Neither CGRP (10(-7) and 10(-6) M) nor AM (10(-7) and
      10(-6) M) had significant effects on the basal release of serotonin and the amino
      acids tested in this study. However, CGRP produced statistically significant
      increases in the K+-evoked release of Asp and Glu, whereas AM failed to do so.
      Neither AM nor CGRP (10(-7) and 10(-6) M) showed any significant effects on the
      K+-evoked release of serotonin, GABA and Gly. Present data suggest that the
      stimulatory effects of CGRP on the release of Asp and Glu were exerted by
      distinct types of CGRP receptors.

PMID- 17532570
TI  - Learned defense response to hypoxia in newborn mice.
AB  - In newborns, hypoxia elicits defensive behaviors including awakening from sleep,
      body movements and crying. An inability to produce this defense response is a
      risk factor for sudden infant death syndrome and other respiratory control
      disorders. In this study, we examined the possibility that the defense response
      to hypoxia in newborns is partly determined by early exposure to hypoxia. We
      explored this possibility in 6-day-old mice, which resemble human preterm infants
      of approximately 25-30 weeks' gestational age. Ultrasonic vocalizations (USVs)
      were recorded as a marker for the defense response to hypoxia. In a conditioning
      experiment, newborn mice were exposed to two artificial odors (conditioned
      stimuli, CS). For acquisition (two trials), pups were exposed to one odor (CS+)
      in a hypoxic gas mixture (10% O2, which was the unconditioned stimulus, US) and
      to another odor (CS-) in air. Then, the pups were exposed to each odor while
      breathing air. Newborn mice produced significantly more USVs when exposed to the
      odor previously paired with hypoxia than to the control odor. Thus, associative
      learning may shape the defense response to hypoxia in newborns.

PMID- 17532571
TI  - Serum folate concentrations in patients with cortical and subcortical dementias.
AB  - Folic acid is believed to play a role in protection from oxidant stress. Low
      levels of folic acid had been found in serum from patients with Alzheimer disease
      (AD). Folate concentration was evaluated in sera from 136 patients with cortical
      dementia [AD, n=108; frontotemporal dementia (FTD), n=28], 57 patients with
      subcortical dementia [Lewy body disease (LBD), n=9; corticobasal degeneration
      (CBD), n=5; progressive supranuclear palsy (PSP), n=6; Parkinson disease with
      dementia (PD-Dem), n=37], and 76 nondemented, healthy age-matched people. Serum
      folic acid levels were decreased in patients with AD and FTD as compared with
      either controls or patients with subcortical dementia (3.60+/-2.22 and 5.37+/
      2.92 microg/L versus 6.87+/-3.50 microg/L, respectively; P<0.01). A tendency
      towards decreased folate concentration was found in LBD and CBD, but not to a
      significant extent. The highest proportion of folate-deficient patients was found
      in CBD, FTD and AD (respectively, 60, 48.2 and 46.3% versus 7.9% in controls;
      P<0.001). Folate deficiency characterizes FTD as well as AD. These differences
      observed among different clinical dementing syndromes may be related to
      neocortical damage.

PMID- 17532572
TI  - Anxiety sensitivity and pain: generalisability across noxious stimuli.
AB  - Anxiety sensitivity, a fear of anxiety-related symptoms, has been associated with
      a heightened experience of pain, especially within women. The majority of
      experimental studies investigating this association have relied heavily on the
      cold pressor technique as a means of pain induction, limiting the
      generalisability of results. The aim of the current study was to extend previous
      research by using two types of pain stimuli (cold and heat) to determine whether
      the link between anxiety sensitivity and pain generalises beyond cold pressor
      pain. The pain experience of 125 participants in response to these stimuli was
      assessed using threshold and tolerance readings, as well as subjective pain
      ratings. Results indicated a positive association between anxiety sensitivity and
      subjective pain, with this association observed primarily in females. Although
      analysis also indicated a basic generalisability of results across pain stimuli,
      anxiety sensitivity effects appeared to be especially pronounced during heat
      stimulation. These findings suggest that those high in anxiety sensitivity may
      respond more negatively to specific types of pain. Possible implications along
      with suggestions for future research are discussed.

PMID- 17532573
TI  - Heterophyosis: risk of ectopic infection.

PMID- 17532574
TI  - Tissue injury by hot fluid containing nitrogen mustard.
AB  - Nitrogen mustards are analogous to sulfur mustard and have similar toxic effects
      on tissues. With the recent surge in terror activity, mustard could be used by
      terrorists. Recently a group of patients suffered from skin injury caused by hot
      fluid containing nitrogen mustard were treated. All the patients displayed eye
      symptoms such as eye pain, photophobia, excessive tearing, and blurred vision.
      One patient suffered from severe inhalation injury. Laboratory examination showed
      the decrease of white blood cell count, which may result from the loss of
      neutrophils. At the same time, platelets were at lower level during the first 8
      days and gamma-glutamyltransferase (gamma-GT), a marker of oxidative stress, was
      significantly increased.

PMID- 17532575
TI  - Evaluation of serum procalcitonin concentration in the ICU following severe burn.
AB  - The goal of the study was to analyse plasma procalcitonin (PCT) concentrations
      during infectious events of burns in ICU. Clinical and laboratory data were
      collected at admission and twice a week in burned patients admitted with a total
      body surface area (TBSA) >20%. Procalcitonin was determined using both a semi
      quantitative detection (PCT-Q) and a quantitative immunoluminometric method (PCT
      Lumi). A total of 359 time points in 25 consecutive patients with 40+/-17% (20
      86%) TBSA burned, defined as a procalcitonin concentration associated with an
      inflammatory status according to society critical care medicine definition, were
      made. The principal site of infection was the respiratory tract (84% of patients
      required mechanical ventilation). PCT-Lumi values corresponded to the four semi
      quantitative ranges of PCT-Q and statistically reflected the simultaneously
      observed inflammatory status (Kruskall-Wallis test). The area under the receiver
      operating characteristic curve for C-reactive protein (CRP) was higher than those
      for PCT and white blood cell (WBC) count, but this difference was not
      significant. The optimum PCT cut-off value was 0.534 ng/ml with sensitivity and
      specificity of 42.4% and 88.8%, respectively. However, PCT does not appear to be
      superior to C-reactive protein (CRP) and white blood count (WBC) as diagnosis
      marker of sepsis in burns. PCT is not sufficient to diagnose and to follow
      infection in burns admitted in ICU.

PMID- 17532576
TI  - Rape blame as a function of alcohol presence and resistance type.
AB  - Attributions of rape blame may be related to variables such as alcohol presence
      and resistance type used during a sexual assault. The current study sought to
      assess participants' attributions of responsibility for a sexual assault based on
      these two variables through the use of several written scenarios. Two hundred and
      thirteen male and female college students participated in the study. Results
      indicated that responsibility ratings given to the victim varied by the presence
      of alcohol but not by resistance type. If the female target had been drinking,
      she was judged as being more responsible for the assault than if she had not been
      drinking. However, how she resisted the assault did not affect ratings of her
      responsibility. Additionally, participant gender was found to not be an important
      factor for attributing blame to the woman target. Future research should focus on
      two important factors: 1) how participants' judgments of blame may change during
      actual alcohol administration and 2) how the use of video, rather than written
      vignettes, may produce stronger effects.

PMID- 17532578
TI  - [Detection of ica genes and slime production in a collection of Staphylococcus
      epidermidis strains from catheter-related infections in neutropenic patients].
AB  - Slime production, principal virulence factor of Staphylococcus epidermidis
      associated with catheter-related infections is mediated by icaADBC operon wich
      expression is subject to phase variation. Reversible transposition of IS256
      element into this operon is one of the most important mechanisms of biofilm
      phenotypic variation. Our study compared 28 S. epidermidis strains from catheter
      related infection to 28 strains from nasal carriage concerning slime production
      on Congo red agar plate and ica genes and IS256 presence by PCR. ica operon was
      present among all slime-producing strains, and was absent among slime-negative
      strains. Only 79% of ica-positive strains were slime producers and no insertion
      of IS256 element was detected inside ica genes. A significative difference was
      found between catheter-related infections strains and commensal ones in terms of
      oxacillin (67,8 versus 35,7%) and ofloxacin resistance (75 versus 35,7%), slime
      production (64,2 versus 28,5%), phase variability (46,4 versus 7,1%) and ica
      genes presence (82,1 versus 35,7%). Our study demonstrates the role of ica genes,
      of phenotypic variability of slime production and antibiotic multiresistance as
      virulence factors of S. epidermidis associated with catheter-related infections;
      it confirms also the complexity and the diversity of regulation mechanisms
      implicated in biofilm formation.

PMID- 17532577
TI  - Correlation of molecular response as measured by 18-FDG positron emission
      tomography with outcome after chemoradiotherapy in patients with esophageal
      carcinoma.
AB  - PURPOSE: To determine whether 18-fluorodeoxyglucose positron emission tomography
      (PET) computed tomography scans predict the pathologic complete response and
      disease-free and overall survival in patients with esophageal carcinoma
      undergoing definitive or preoperative chemoradiotherapy. METHODS AND MATERIALS:
      The records of patients with esophageal carcinoma presenting for definitive or
      preoperative treatment and undergoing pre- and post-treatment 18
      fluorodeoxyglucose PET-computed tomography scans were retrospectively reviewed.
      The histologic type, T stage, and nodal status were the variables investigated to
      determine a relationship with the baseline standardized uptake value (SUV) of the
      primary tumor at diagnosis. We also attempted to determine whether a relationship
      exists between the percent decrease in SUV and a pathologic complete response,
      overall and disease-free survival. RESULTS: A total of 81 patients, 14 women and
      67 men, underwent 18-fluorodeoxyglucose PET-computed tomography scanning before
      treatment and 63 also had post-treatment scans. T stage and tumor location
      predicted in univariate, but not multivariate, analysis for the initial SUV. Of
      the patients with a postchemoradiotherapy SUV of <2.5, 66% had tumor in the
      surgical specimen and 64% of patients had positive lymph nodes at surgery that
      were not imaged on the postchemoradiotherapy PET scan. A trend existed for post
      treatment SUV and the days from radiotherapy to surgery to predict for a
      pathologic complete response (p = 0.09 and p = 0.08, respectively). The post
      treatment SUV predicted for disease-free survival in the definitive
      chemoradiotherapy group (p = 0.01). CONCLUSIONS: A correlation was found between
      the depth of tumor invasion and the baseline SUV. The post-treatment SUV
      predicted for disease-free survival in the definitive chemoradiotherapy group.
      Caution should be exercised in using post-treatment PET scans to determine the
      necessity for surgical resection.

PMID- 17532579
TI  - Anoxia or oxygen and glucose deprivation in SH-SY5Y cells: a step closer to the
      unraveling of neuroglobin and cytoglobin functions.
AB  - Several studies support the hypothesis that neuroglobin and cytoglobin play a
      protective role against cell death when cellular oxygen supply is critical.
      Although the underlying molecular mechanisms are unknown, previous reports
      suggest that this protection can be realised by the fact that they act as ROS
      scavengers. In this study, expression of neuroglobin and cytoglobin was evaluated
      in a human neuroblastoma cell line (SH-SY5Y) under conditions of anoxia or oxygen
      and glucose deprivation (OGD). The cells could survive prolonged anoxia without
      significant loss of viability. They became anoxia sensitive when deprived of
      glucose. OGD induced significant cell death after 16 h resulting in 54% dead
      cells after 32 h. Necrosis was the main process involved in OGD-induced cell
      death. After reoxygenation, apoptotic neurons became more abundant. Real-time
      quantitative PCR and Western blotting revealed that neuroglobin and cytoglobin
      were upregulated, the former under OGD and the latter under anoxic conditions.
      Under OGD, cell survival was significantly reduced after inhibiting cytoglobin
      expression by transfection with antisense ODN. Moreover, cell survival was
      significantly enhanced by neuroglobin or cytoglobin overexpression. When
      neuroglobin or cytoglobin protein expression increased or decreased, the H(2)O(2)
      level was found to be lower or higher, respectively. We conclude that neuroglobin
      or cytoglobin act as ROS scavengers under ischemic conditions.

PMID- 17532580
TI  - Thyroid hormone responsive genes in the murine hepatocyte cell line AML 12.
AB  - Thyroid hormone (T3) plays an important role in gene regulation in the liver.
      Previous studies have been done in complex systems such as animal models, or in
      transformed malignant hepatic cell lines in which thyroid hormone receptor (TR)
      was over-expressed by co-transfection. Therefore, the aim of this study was to
      characterize T3-responsive genes in a simple system, by using a non-transformed
      hepatic cell line that is able to express sufficient amounts of endogenous TRs.
      For this purpose we used the murine non-transformed hepatocyte cell line AML 12.
      We performed analyses using a cDNA microarray containing 15,000 murine genes. We
      found 12 genes to be up-regulated and 5 genes to be down-regulated in the
      presence of T3. For some of the genes not previously known to be regulated by T3,
      we confirmed the regulation by T3 using real-time PCR. Our data in AML 12 cells
      provide a simple and physiologically relevant system to study T3 action, without
      the influence of neoplastic transformation or artificial TR over-expression.
      Furthermore, our data describe novel T3 responsive genes and provide insight into
      the role of T3 in important processes such as cholesterol metabolism, bile acid
      secretion, oncogenesis, among others, that can be tested in future experiments in
      vivo.

PMID- 17532581
TI  - Comparative diagnostic potential of three serological tests for abortive Q fever
      in goat herds.
AB  - Performances of an ELISA, an immunofluorescence assay (IFA) and a complement
      fixation test (CFT) were assessed for detecting antibodies against Coxiella
      burnetii after Q fever abortions in naturally infected goats. The goal of the
      study was to provide information useful for veterinary serodiagnosis in regard to
      categories of goats either experiencing Q fever abortion or not, blood sampling
      times and recommended cut-offs. The study was conducted on eight goat herds with
      evidence of C. burnetii abortions. In each herd, at least 5 goats that had
      aborted and 10 goats prior to parturition or at term were monitored 15, 30 and 60
      days (D15, D30, D60) after the onset of Q fever abortion. The overall CFT results
      distribution did not differ between the two groups of goats and showed poor
      agreement with the ELISA results. In contrast, the ELISA and IFA results revealed
      comparable significant differences, but overall the ELISA test was slightly more
      sensitive than the IFA test. Seroprevalence, according to ELISA and IFA
      respectively, was higher in the aborting (88% and 82%) than in the non-aborting
      group (60% and 50%). High levels of serum antibodies were detected in goats post
      abortion with an average of 114 %OD using ELISA and a log10(titer) of 2.4 using
      IFA. Strongly positive ELISA (%OD>80) and positive IFA results
      (log10(titers)>1.9) were significantly associated with abortion. Sampling on D15
      gave the best association with ORs of 10 for ELISA and 6 for IFA. The practical
      interest of these results is discussed.

PMID- 17532582
TI  - Survival of Swiss-Webster mouse cerebellar granule neurons is promoted by a
      combination of potassium channel blockers.
AB  - Cultured cerebellar granule neurons (CGN) are commonly used to assess
      neurotoxicity, but are routinely maintained in supraphysiological (25 mM)
      extracellular K(+) concentrations [K(+)](o). We investigated the effect of
      potassium channel blockade on survival of CGN derived from Swiss-Webster mice in
      supraphysiological (25 mM) and physiological (5.6 mM) [K(+)](o). CGN were
      cultured for 5 days in 25 mM K(+), then in 5.6 mM K(+) or 25 mM K(+) (control).
      Viability, assayed 24 h later by 3-(4,5-dimethylthiazolyl-2)-2,5
      diphenyltetrazolium bromide (MTT) reduction and by lactate dehydrogenase (LDH)
      release, was approximately 50% in 5.6 mM K(+) versus 25 mM K(+) (p<.001).
      Potassium channel blockers, 2 mM 4-aminopyridine (4-AP), 2 mM tetraethylammonium
      (TEA) or 1 mM Ba(2+), individually afforded limited protection in 5.6 mM K(+).
      However, survival in 5.6 mM K(+) with a combination of 4-AP, TEA and Ba(2+) was
      similar to survival in 25 mM K(+) without blockers (p<.001 versus 5.6 mM K(+)
      alone). CGN survival in 25 mM K(+) was attenuated 25% by 2 microM nifedipine
      (p>.001), but nifedipine did not attenuate neuroprotection by K(+) channel
      blockers. Together, these results suggest that the survival of CGN depends on the
      K(+) permeability of the membrane rather than the activity of a particular type
      of K(+) channel, and that the mechanism of neuroprotection by K(+) channel
      blockers is different from that of elevated [K(+)](o).

PMID- 17532583
TI  - Antibacterial and antifungal activity of Cassia fistula L.: an ethnomedicinal
      plant.
AB  - Hexane, chloroform, ethyl acetate, methanol and water extracts from the flower of
      Cassia fistula (an ethnomedicinal plant) were tested against bacteria and fungi.
      All the extracts exhibited antibacterial activity against Gram-positive organisms
      with minimum inhibitory concentrations (MIC) between 0.078 and 2.5 mg/ml. Among
      the Gram-negative bacteria, only Pseudomonas aeruginosa was susceptible to the
      extracts. Ethyl acetate crude extract was fractionated using chromatographic
      techniques. A crystal was isolated, which was confirmed as 4-hydroxy benzoic acid
      hydrate using X-ray crystallography. It exhibited antifungal activity against
      Trichophyton mentagrophytes (MIC 0.5 mg/ml) and Epidermophyton floccosum (MIC 0.5
      mg/ml).

PMID- 17532584
TI  - Antioxidant activity relates to plant part, life form and growing condition in
      some diabetes remedies.
AB  - Selection, collection and preparation of 35 plant species used by traditional
      healers in the boreal regions of Canada for treatment of the symptoms of diabetes
      were supported empirically by antioxidant activity of the plants. Because
      antioxidants fluctuate with growth parameters and environmental factors, these
      remedies were evaluated in relation to the affect of plant part, life form and
      growing condition on the level of activity. The parts used here more frequently
      as medicines were roots and bark. Activity (IC(50)) of the bark extracts used
      medicinally averaged to 21.38+/-3.84 ppm while root extracts used medicinally had
      an IC(50) of 185.11+/-32.18 ppm in a free radical DPPH assay. In contrast the
      analysis of extracts of overall parts (medicinal or not) in these species found
      leaves and bark to have the least activity (112.22+/-30.63 ppm and 123.02+/-21.13
      ppm, respectively). The highest activity was found in tree extracts (24.88+/-3.32
      ppm) as compared to herbs and shrubs, and increased activity was found in plant
      extracts from growing conditions of decreased water/fertility. The antioxidant
      activity of these traditional plant remedies have the potential to be partially
      deduced through environment signals interpreted by the traditional herbalist.

PMID- 17532585
TI  - The measurement of open apices of teeth to test chronological age of over 14-year
      olds in living subjects.
AB  - Age determination in living subjects is a problem of increasing interest in our
      community, due to the increasing numbers of individuals without identification
      papers, who have immigrated illegally or committed crimes, and for whom it is
      necessary to verify whether they have reached the age of 14 years in order to be
      charged legally. Although the most widespread methods for age estimation refer to
      skeletal or dental analysis, these methods do present some drawbacks for
      identification of the age of 14. The aim of the present study is to discriminate
      between children who are or are not 14 years of age or older by measuring the
      open apices of teeth. We evaluated the OPGs of 447 persons aged between 12 and 16
      years, of Italian, Croatian and Slovenian nationality. For each individual,
      dental maturity was estimated using the number of the seven left permanent
      mandibular teeth with root development complete, and normalized measurement of
      the open apices of the third molar. The results revealed that an individual is
      considered to be 14 years of age or older if all seven left permanent mandibular
      teeth have closed apices and the normalized measurement of open apices of the
      third molar is lower than 1.1.

PMID- 17532586
TI  - Rotavirus associated acute encephalitis/encephalopathy and concurrent
      cerebellitis: report of two cases.
AB  - It is known that rotavirus gastroenteritis can accompany some neurological
      manifestations, including encephalitis/encephalopathy or seizures. However, the
      detailed pathogenesis involved has not been fully understood. To date, acute
      cerebellitis associated rotavirus gastroenteritis has not been previously
      reported, except for one case. Herein, we describe two cases of acute
      encephalitis/encephalopathy and concurrent cerebellitis, associated rotavirus
      gastroenteritis. Following vomiting and diarrhea, case 1 experienced convulsions
      and consciousness disturbance and case 2, transient loss of consciousness with
      eye deviation. After these symptoms subsided, cerebellar signs became evident and
      a brain MRI showed cerebellar involvement in both cases. Both cases showed speech
      disturbances, such as mutism, slow speech and dysarthria. In this report, we will
      discuss the possible pathogenesis of rotavirus associated acute
      encephalitis/encephalopathy and concurrent cerebellitis.

PMID- 17532587
TI  - Hypomanic mood in a child patient treated with interferon-alpha 2a: case report.
AB  - We report on a male child born in Rumania, adopted by an Italian family, and who
      at 10 years of age was submitted to interferon-alpha 2a therapy for chronic
      hepatitis B. About 30 days after the beginning of the treatment he developed
      hypomanic mood and psychogenic seizures. Psychological evaluation showed
      hyperactivity, distractibility, excessive talkativeness, grandiosity and racing
      thoughts. Temperamental traits were characterized by an elevated emotionality.
      The patient was successfully administered risperidone and cognitive-behavioral
      therapy; six months of treatment with interferon led to positive outcome of
      hepatitis B. Since affective symptoms may occur in children treated with IFN, a
      careful evaluation of psychiatric disturbances and adequate intervention are
      needed.

PMID- 17532588
TI  - [Epidemiology of Haemophilus influenzae strains collected in 2004 in France and
      in vitro assessment of their susceptibility to antibiotics].
AB  - OBJECTIVES: The aim of this study was to describe the epidemiology of H.
      influenzae strains collected in 2004 at the National Reference Center and to
      evaluate their susceptibility to various antibiotics. METHODS: Demographic and
      clinical characteristics, capsular serotyping by slide agglutination with
      specific antisera, beta-lactamase by a chromogenic cephalosporin test
      (Nitrocefin) and MICs of amoxicillin, co-amoxiclav, cefpodoxime, cefaclor,
      cefuroxime, cefotaxime, erythromycin, pristinamycin and telithromycin by agar
      dilution method on Haemophilus Test Medium were determined for each strain.
      RESULTS: 807 strains of H. influenzae were identified: 41.8% from bronchial
      secretions (BS), 16.2% from conjunctivitis, 6.6% from otitis media (OM), 4.2%
      from CSF and 8.6% from blood cultures. 95.6% of strains was not capsulated and
      4.4% was of serotype b, e, or f. 26.3% of strains was beta-lactamase producing
      (TEM type). 185 isolates (22.8% of total strains) had reduced susceptibility to
      beta-lactams due to modification of the target associated or not with beta
      lactamase production. When beta-lactamase was produced, the MICs of amoxicillin
      increased, but the activity of the other antibiotics was unchanged. Low BLNAR
      strains showed an increase in the MICs of all beta-lactams. This increase was
      weak and variable according to beta-lactams. Pristinamycin and telithromycin
      activities were unchanged against these strains. Two strains were resistant to
      erythromycin. CONCLUSIONS: Theses results show that both beta-lactamase and
      modifications of the target are widespread among H. influenzae strains isolated
      in France. Cefpodoxime remains the most active compounds against H. influenzae,
      whatever the resistance mechanisms, followed by pristinamycin, telithromycin, and
      co-amoxiclav.

PMID- 17532589
TI  - Comparison of an immunochromatographic rapid test with enzyme-linked
      immunosorbent assay and polymerase chain reaction for the detection of Shiga
      toxins from human stool samples.
AB  - Rapid detection of enterohemorrhagic Escherichia coli is important for its
      successful treatment. We have evaluated the immunochromatographic Duopath
      Verotoxin-test for detection of Shiga toxins, in comparison with enzyme-linked
      immunosorbent assay and polymerase chain reaction, on 240 clinical human stool
      samples. The Duopath-test showed a lower sensitivity and specificity.

PMID- 17532590
TI  - Molecular epidemiology of group A streptococcus causing scarlet fever in northern
      Taiwan, 2001-2002.
AB  - In this study, 830 Streptococcus pyogenes isolates collected between 2001 and
      2002 from patients with scarlet fever in northern Taiwan were analyzed by M
      protein gene (emm) sequence typing, pulsed-field gel electrophoresis (PFGE), and
      antimicrobial susceptibility testing. A total of 21 emm types and 56 PFGE
      patterns were identified. The most frequent emm types were emm1 (29.2%), emm4
      (24.1%), emm12 (19.0%), emm6 (15.8%), stIL103 (5.7%), and emm22 (1.9%).
      Antimicrobial resistance profiles were determined, and resistance to erythromycin
      (24.6%), clindamycin (2.0%), and chloramphenicol (1.3%) was detected. Five major
      emm types (emm4, emm12, emm1, emm22, and emm6) accounted for 95.6% of the
      erythromycin-resistant isolates. The decreased prevalence of erythromycin
      resistant emm12 strains coincided with the overall decrease in erythromycin
      resistance from 32.1% in 2001 to 21.1% in 2002 in Taiwan. Five major clones
      (emm4/2000, emm12/0000, emm4/2010, emm1/1000, and emm22/8100) represented 72.1%
      of the erythromycin-resistant isolates. The survey of group A Streptococcus emm
      types, genetic diversity, and antibiotic resistance has direct relevance to
      current antimicrobial use policies and potential vaccine development strategies.

PMID- 17532591
TI  - Development and evaluation of real-time polymerase chain reaction assays on whole
      blood and paraffin-embedded tissues for rapid diagnosis of human brucellosis.
AB  - This study aimed at developing a real-time polymerase chain reaction (PCR) assay
      for the rapid diagnosis of human brucellosis on clinical specimens. Three assays
      with hybridization probe detection on the LightCycler instrument were developed
      and compared targeting the 16S-23S internal transcribed spacer region (ITS) and
      the genes encoding for omp25 and omp31. All assays showed 100% analytical
      sensitivity and 100% specificity when tested on 28 consecutive clinical isolates
      of Brucella sp. and 19 clinical isolates of common Gram-negative and Gram
      positive bacterial pathogens, respectively. The ITS assay was the most sensitive
      with a limit of detection of 2 genome equivalents per PCR reaction. This assay
      was then clinically validated prospectively with 354 samples (351 whole blood
      samples and 3 paraffin-embedded tissues) collected from 340 patients, 24 samples
      from patients with active brucellosis including 2 relapsing cases, 31 with
      treated brucellosis, and 299 seronegative patients where brucellosis was
      initially suspected. The clinical sensitivity, specificity, and positive and
      negative predictive values of the ITS assay were 66.7%, 99.7%, 94.1%, and 97.6%,
      compared with culture at 77%, 100%, 100%, and 97.3%, respectively. The difference
      in sensitivity between culture and ITS-PCR was not statistically significant (P =
      0.71). Both relapsing cases were PCR positive. Treated patients were PCR
      negative. All 3 assays were positive on tissue samples, but the omp25 and omp31
      assays did not detect Brucella sp. DNA in blood samples. Because omp31 is not
      present in Brucella abortus, these data indicate that the 28 tested isolates are
      most likely Brucella melitensis. ITS-PCR is rapid and could augment the clinical
      laboratory diagnosis of human brucellosis.

PMID- 17532592
TI  - Antimicrobial resistance among invasive isolates of Streptococcus pneumoniae
      collected across Canada.
AB  - Between 2002 and 2003, 736 nonduplicate Streptococcus pneumoniae isolated from
      blood cultures were collected from 7 of 10 Canadian provinces (10 tertiary care
      centers). Microdilution broth susceptibility testing was performed using the
      method prescribed by the Clinical Laboratory Standards Institute. Of the
      isolates, 16.85% were nonsusceptible to penicillin and 5.4% were highly
      resistant. Of the S.pneumoniae, 14.1% had reduced susceptibility to erythromycin
      and 47% had been accounted for by the M phenotype. No isolates were recovered
      that were resistant to telithromycin. Only 6 isolates were resistant to
      levofloxacin and gatifloxacin. Of these, 5 strains had intermediate
      susceptibility to moxifloxacin and 1 was considered susceptible. The rates
      observed in this study are in keeping with previous surveillance studies among
      noninvasive isolates.

PMID- 17532593
TI  - Acrophialophora fusispora: an emerging agent of human mycoses. A report of 3 new
      clinical cases.
AB  - Acrophialophora fusispora is a soil-borne fungus, which is emerging as a human
      pathogen. Only four cases of human infection had been described previously. We
      describe three more cases, two from Europe and one from India. Since this fungus
      has been misidentified in several other cases, it is probably more frequent than
      first thought.

PMID- 17532594
TI  - Unusual concurrent detection by polymerase chain reaction of Bartonella henselae
      and parvovirus b19 in an immunocompetent child with erythema nodosum and hepatic
      granulomatous disease.
AB  - We report an unusual case of documented Bartonella henselae genotype I from
      hepatic tissue in an Italian immunocompetent girl presenting with erythema
      nodosum and hepatic granulomata. Polymerase chain reaction (PCR) was performed on
      biopsied liver sample to confirm the etiologic role of B. henselae and to
      identify the genetic variant of this organism. A PCR on the same liver biopsy for
      parvovirus B19 was also positive, but the clinical meaning of this was not clear.

PMID- 17532595
TI  - Sex and region difference of the expression of ERK in prenatal stress offspring
      hippocampus.
AB  - Prenatal stress is known to cause neuronal loss and oxidative damage in the
      hippocampus of offspring rats. The underlying molecular mechanism has not been
      fully understood. The extracellularsignal-regulated kinase (ERK1/2) is recruited
      when the brain undergoes synaptic plasticity and remodeling. In the present
      study, we used Western blotting and immunohistochemistry techniques to examine
      the effects of prenatal restraint stress (PNS) on the expression of
      phosphorylated ERK (p-ERK) and total ERK. Pregnant rats in the PNS group were
      exposed to restraint stress on day 14-20 of pregnancy three times daily for
      45min. One-month-old offspring rats were used in this experiment. PNS treatment
      increased the expression of p-ERK2 compared to that in the control female
      offspring rats and total ERK2 in female offspring hippocampus compared with that
      of control group. No significant changes in the amounts of total ERK1 of
      prenatally offspring hippocampus were observed in both genders compared with
      control animals. ERK immunodensity was significantly increased in PNS groups in
      CA3 field in male offspring hippocampus compared with control animals. ERK
      optical density was significantly increased in PNS female offspring hippocampus
      CA1, CA3 and CA4 region. However, ERK optical density was not significantly
      different between male control and PNS groups in CA1, CA4 fields and DG in
      offspring hippocampus. These findings suggest the sex and region-dependent
      effects of prenatal stress on the expression of ERK in offspring hippocampus. ERK
      expression changes induced by prenatal stress may contribute to hippocampus
      synaptic plasticity changes of the offspring.

PMID- 17532596
TI  - Development of the Diabetes Health Threat Communication Questionnaire (DHTCQ).
AB  - OBJECTIVES: (1) To develop a brief instrument, the Diabetes Health Threat
      Communication Questionnaire (DHTCQ) to measure diabetes patients' (type1 and type
      2) perceptions of the health threat communication process (i) at time of
      diagnosis and (ii) since diagnosis; (2) to assess the measure' psychometric
      properties. METHODS: Data from a pilot study (n=110) and a prospective
      longitudinal study (n=158, within 3 months of diagnosis and n=147, 6 months after
      baseline) were examined in order to demonstrate reliability and validity of the
      DHTCQ. RESULTS: Principal components factor analysis revealed 2 meaningful
      factors (Reassurance and Threat) with satisfactory internal consistency
      (Cronbach' alpha) and adequate test-retest reliability. Correlational analyses
      supported the measure' construct validity. CONCLUSION: Initial support for the
      psychometric properties of the DHTCQ was shown. Perceptions of health threat
      communication were associated with patients' illness representations of diabetes
      (beliefs and feelings about diabetes and its treatment). PRACTICE IMPLICATIONS:
      The DHTCQ may be used to assess patient perceptions of health communication and
      shape subsequent communication. The findings may help to improve
      practitioner/patient interaction leading to more adaptive representations of
      diabetes.

PMID- 17532597
TI  - Laparoscopic surgery is safe for large adrenal lesions.
AB  - INTRODUCTION: Laparoscopic adrenalectomy has surpassed open adrenalectomy as the
      gold standard for excision of benign adrenal lesions. The size threshold for
      offering laparoscopic adrenalectomy is controversial as the prevalence of
      adrenocortical carcinoma increases with increasing tumour size. The aim of this
      paper was to assess the safety of laparoscopic adrenalectomy for large adrenal
      tumours (tumours > or = 60 mm). METHODS: A retrospective cohort study of patients
      who underwent adrenalectomy in a single unit during the period 1995-2005 was
      undertaken. RESULTS: One hundred and seventy patients with 173 tumours were
      included in this study. Of these, 29 were > or = 60 mm in size, and 16 of these
      patients underwent laparoscopic adrenalectomy. There were 8 adrenocortical
      carcinomas in the group with tumours > or = 60 mm in size. Five of these patients
      underwent an open adrenalectomy, while 2 and 1 patients had laparoscopic and
      laparoscopic converted to open adrenalectomy respectively. Four of the patients
      undergoing open adrenalectomy died of their disease while 1 is alive with
      recurrence 3 years later. The 3 patients who underwent either laparoscopic or
      laparoscopic converted to open adrenalectomy are alive without evidence of
      disease after 18 months follow up. CONCLUSION: Our data show that patients with
      tumours > or = 60 mm with no preoperative or intraoperative evidence of
      malignancy can undergo laparoscopic adrenalectomy without evidence of recurrence
      on short term follow up. These findings are concordant with the growing body of
      literature supporting laparoscopic adrenalectomy for potentially malignant
      tumours > or = 60 mm in size without preoperative or intraoperative features of
      malignancy.

PMID- 17532598
TI  - [Systemic analgesia adapted to the children's condition].
AB  - A concept of balanced analgesia using nonsteroidal anti-inflammatory drugs
      (NSAIDs), paracetamol (acetaminophen), opioids, and corticosteroids can also be
      used in patients with pre-existing illnesses. NSAIDs are the most effective
      treatment for acute pain of moderate intensity in children; however, these drugs
      should be avoided in patients at increased risk for serious side effects, e.g.
      patients with renal impairment, bleeding tendency, or extreme prematurity. NSAIDs
      can be given with minimal risks to the younger child with mild to moderate
      asthma, and, in these patients, the use of steroids can be encouraged; in
      addition to their antiemetic and analgesic action, a beneficial effect on asthma
      symptoms can be expected. In the non-intubated child with cerebral trauma,
      exaggerated sedation caused by opioids and increased bleeding tendency caused by
      NSAIDs must be avoided. In neonates and small infants, the oral administration of
      sucrose or glucose is helpful to minimize pain reaction during short
      uncomfortable interventions.

PMID- 17532599
TI  - Urinary detection of podocyte injury.
AB  - Glomerular epithelial cell (podocyte) biology has been focused on in the last few
      years. The emerging understanding in podocyte biology has improved the molecular
      mechanism knowledge in many glomerular diseases. Urinary podocyte count and
      measurement of urinary podocyte specific markers (nephrin and podocalyxin) have
      been developed to detect podocyte injury. We discuss the emerging clinical
      importance of the urinary podocyte count in experimental and human glomerular
      disease, as well as measurement of urinary podocyte specific marker.

PMID- 17532600
TI  - Receptor affinity, stability and binding mode of Shiga toxins are determinants of
      toxicity.
AB  - The closely related Shiga toxins, Shiga toxin 1 (Stx1) and Shiga toxin 2 (Stx2),
      can bind to Gb3 receptors. However, Stx2-producing enterohemorrhagic Escherichia
      coli (EHEC) strains are more commonly associated with serious human disease
      (viz., hemolytic-uremic syndrome) than Stx1-producing strains. To clarify the
      relationship between properties and toxicity of these toxins, we constructed and
      analyzed a hybrid holotoxin composed of Stx2A and Stx1B, designated as Stx2A1B,
      and a B subunit chimeric holotoxin composed of Stx2A and Stx2B (III V),
      designated as Stx2A2B (III V). The affinity of Stx2A1B to Gb3 was lower than that
      of Stx1, higher than that of Stx2 and identical to that of Stx2A2B (III V). On
      the other hand, the 50% lethal dose (LD(50)) for mice of Stx2A1B was lower than
      that of Stx1, but higher than that of Stx2. These results suggested that
      pathogenicity in mice was inversely related to the receptor affinity of the
      holotoxins. However, LD(50) of Stx2A1B was not identical to that of Stx2A2B (III
      V). Gel filtration analysis indicated that Stx2A2B (III V) was relatively less
      stable than Stx2A1B. Moreover, cross-linking experiments demonstrated that the
      modes of cell surface binding of Stx2A2B (III V) and Stx2A1B were different.
      These results indicated that the receptor affinity, stability and binding mode of
      Shiga toxins might be important determinants for toxicity in mice.

PMID- 17532601
TI  - Memory impairments in posttraumatic stress disorder are related to depression.
AB  - The present study focuses on verbal learning and memory alterations in refugees
      with posttraumatic stress disorder, and whether the alterations are related to
      attention, acquisition, storage, or retrieval. Twenty-one refugees exposed to war
      and political violence with chronic PTSD, were compared to an exposed control
      sample of 21 refugees without PTSD. No differences were found in attention span,
      but tests of verbal memory showed less efficient learning in the PTSD sample.
      Group differences in delayed recall could be explained by learning efficiency. No
      differences were seen in recognition memory. These results indicate that memory
      alterations in PTSD are related to impaired acquisition and less effective
      encoding of the memory material and not to impaired attention span and/or
      impaired retrieval. Controlling for specific PTSD symptom clusters and self
      reported depression showed that the intrusion subscale and depressive reactions
      are the most important symptoms in understanding the memory alterations in PTSD.

PMID- 17532602
TI  - Beware of varicose veins in a patient with sturge-weber syndrome.
AB  - This report describes the case of a 21-year-old man with a history of Sturge
      Weber syndrome and varicose veins. Examination of the left lower limb revealed
      the presence of significant port-wine staining, and hypertrophy. Duplex
      examination revealed a severely hypoplastic deep venous system with a tortuous,
      dilated, long saphenous vein, which was competent and responsible for a
      significant proportion of venous return from the left lower limb, thus confirming
      the diagnosis of Klippel-Trenaunay syndrome. The patient was counseled regarding
      the implications of the diagnosis and was treated conservatively. The association
      between these two rare syndromes has been previously reported in the nonvascular
      literature. We believe that features of the Sturge-Weber syndrome or other forms
      of mesodermal phakomatosis should alert a clinician to the presence of lower limb
      venous malformations, which will need to be investigated prior to embarking on
      what could be potentially detrimental venous surgery.

PMID- 17532603
TI  - Gender differences in blood flow velocities after carotid angioplasty and
      stenting.
AB  - Gender differences have been demonstrated in blood flow velocities by duplex
      ultrasonography (DU) in patients with carotid stenosis. Currently, DU is the most
      widely used method of follow-up monitoring after carotid angioplasty and stenting
      (CAS). To identify possible gender differences in carotid flow velocities, we
      analyzed our experience with DU obtained before and immediately after CAS. In a
      series of 47 CAS procedures over a 2.5-year period performed in 31 men and 15
      women, carotid angiograms and duplex flow velocities were obtained preoperatively
      and within 24 hr after CAS. Carotid velocity profiles were compared with the
      angiographic degree of carotid stenosis. Gender differences in blood velocities
      were assessed using parametric and nonparametric statistical tests. Overall,
      women had median blood velocities 5-10% higher than men, although the differences
      were not statistically significant. DU obtained immediately after CAS revealed
      that median blood flow velocities were very similar among men and women (P >
      0.4). In conclusion, although women have higher carotid blood flow velocities
      than men do, gender differences are notably absent on follow-up DU after carotid
      stenting. Our data indicate that similar criteria should be used after CAS for
      interpreting carotid velocity profiles in both women and men.

PMID- 17532604
TI  - Endovascular repair of an actively hemorrhaging aortoduodenal fistula.
AB  - Aortoenteric fistulae require urgent definitive intervention and traditionally
      carry a high mortality. We describe a patient who suffered a traumatic aortic
      dissection following an auto versus pedestrian collision. He underwent open
      fenestration of his infrarenal aorta and visceral resection, complicated by
      abdominal sepsis and enterocutaneous fistulae. One month later he developed
      massive hematemesis, and endoscopic examination revealed an aortoduodenal
      fistula. Due to an impassable abdominal wall, a stent-graft repair was performed.
      This report describes the successful use of endovascular techniques to achieve
      immediate hemostasis in an actively hemorrhaging aortoduodenal fistula. An
      endovascular approach provides a valuable option in settings where a hostile
      abdomen precludes the traditional open technique and may serve as a bridge to
      later definitive repair.

PMID- 17532605
TI  - Intraoperative flow measurements are helpful in the treatment of high-inflow
      steal syndrome on a predialysis patient with a brachiocephalic fistula: a case
      report.
AB  - Distal revascularization and interval ligation (DRIL) is currently one of the
      mainstay treatments for severe steal syndrome. However, when high inflow is the
      underlying cause, this technique does not fully address the problem. Here, we
      describe the use of intraoperative flow measurements using transit time
      ultrasound technology to help identify the cause of steal syndrome in a
      predialysis patient (no transonic surveillance) with a brachiocephalic fistula,
      who then was treated successfully by inflow reduction surgery using a bovine
      ureter graft. We believe that inflow reduction might be superior to DRIL in
      treating steal syndrome caused by high inflow and that transit time ultrasound
      might be helpful when transonic treatment is not possible.

PMID- 17532606
TI  - Late presentation of a mycotic popliteal artery pseudoaneurysm in the setting of
      a revised total knee arthroplasty complicated by both prior infection and
      periprosthetic fracture: a case report.
AB  - Reports of adverse arterial events associated with total knee arthroplasty (TKA),
      such as ischemia, thrombosis, arterial injury, or pseudoaneurysm, are relatively
      rare in the orthopedic and vascular literature and are most commonly associated
      with direct trauma to the vessel. Additionally, arterial complications typically
      present within a short postoperative time frame. A delayed presentation of a
      mycotic arterial pseudoaneurysm in the setting of a revision arthroplasty
      complicated by infection and fracture has not, to the best knowledge of the
      authors, been described in the literature. We report the delayed presentation of
      a mycotic pseudoaneurysm in the setting of a revision TKA previously complicated
      by both infection and periprosthetic fracture. One year after fracture repair,
      the patient presented with acute thigh swelling and was diagnosed with a mycotic
      pseudoaneurysm of the right proximal popliteal artery. He was treated with
      surgical excision, reverse saphenous vein interpositional grafting, and a long
      term course of broad-spectrum antibiotics. In the setting of a revision TKA and
      previous complications, the risk of future complications is increased and may not
      always involve direct vascular trauma. In patients with previously infected
      joints and new-onset vascular events, mycotic pseudoaneurysm must be included in
      the differential diagnosis.

PMID- 17532608
TI  - Recurrent neural network modeling of nearshore sandbar behavior.
AB  - The temporal evolution of nearshore sandbars (alongshore ridges of sand fringing
      coasts in water depths less than 10 m and of paramount importance for coastal
      safety) is commonly predicted using process-based models. These models are
      autoregressive and require offshore wave characteristics as input, properties
      that find their neural network equivalent in the NARX (Nonlinear AutoRegressive
      model with eXogenous input) architecture. Earlier literature results suggest that
      the evolution of sandbars depends nonlinearly on the wave forcing and that the
      sandbar position at a specific moment contains 'memory', that is, time-series of
      sandbar positions show dependencies spanning several days. Using observations of
      an outer sandbar collected daily for over seven years at the double-barred
      Surfers Paradise, Gold Coast, Australia several data-driven models are compared.
      Nonlinear and linear models as well as recurrent and nonrecurrent parameter
      estimation methods are applied to investigate the claims about nonlinear and long
      term dependencies. We find a small performance increase for long-term predictions
      (>40 days) with nonlinear models, indicating that nonlinear effects expose
      themselves for larger prediction horizons, and no significant difference between
      nonrecurrent and recurrent methods meaning that the effects of dependencies
      spanning several days are of no importance.

PMID- 17532607
TI  - Major elective surgery for vascular disease in patients aged 80 or more:
      perioperative (30-day) outcomes.
AB  - Although major vascular surgery is performed with increasing frequency in elderly
      people, the impact of age on outcomes is uncertain. We evaluated the
      perioperative (30-day) outcomes for patients who underwent major elective
      vascular operations under general or peripheral anesthesia in their eighties and
      nineties in a 14-year period. Data for all consecutive 3,060 patients (456 of
      them > or years old) who underwent 3,314 elective vascular surgery procedures
      were prospectively entered into a computerized vascular registry. Detailed
      information was collected on patients' preoperative status, type of procedure and
      anesthesia, perioperative outcomes, and predictors of perioperative outcomes. The
      end points of the study were perioperative death and main surgical complications.
      Perioperative all-cause mortality rates varied across operations and were higher
      in elderly than in younger patients (1.4% vs. 0.2%, P = 0.014) after abdominal
      surgery (2.4% vs. 0.1%, P = 0.006) and especially after abdominal aortic aneurysm
      repair (2.8% vs. 0%, P = 0.035). In the elderly cohort, the mortality rate was
      <1% for almost 60% of all operations. In logistic regression analysis, only
      preoperative hypertension (odds ratio [OR] = 72.5, 95% confidence interval [CI]
      9.4-557.6), congestive heart failure (OR = 16.5, 95% CI 2.3-115.9), and
      perioperative cardiac (OR = 20.7, 95% CI 1.6-273.8) and pulmonary (OR = 41.7, 95%
      CI 7.9-218.9) complications were associated with a higher 30-day death risk. In
      this series, perioperative outcomes were not influenced by the type of elective
      surgical procedure. Though overall mortality after major vascular surgery was
      higher in patients > or 80 years old, age per se was not an independent factor of
      a higher perioperative mortality risk or fatal and nonfatal complications.

PMID- 17532609
TI  - Knowledge-based modularization and global optimization of artificial neural
      network models in hydrological forecasting.
AB  - Natural phenomena are multistationary and are composed of a number of interacting
      processes, so one single model handling all processes often suffers from
      inaccuracies. A solution is to partition data in relation to such processes using
      the available domain knowledge or expert judgment, to train separate models for
      each of the processes, and to merge them in a modular model (committee). In this
      paper a problem of water flow forecast in watershed hydrology is considered where
      the flow process can be presented as consisting of two subprocesses -- base flow
      and excess flow, so that these two processes can be separated. Several approaches
      to data separation techniques are studied. Two case studies with different
      forecast horizons are considered. Parameters of the algorithms responsible for
      data partitioning are optimized using genetic algorithms and global pattern
      search. It was found that modularization of ANN models using domain knowledge
      makes models more accurate, if compared with a global model trained on the whole
      data set, especially when forecast horizon (and hence the complexity of the
      modelled processes) is increased.

PMID- 17532610
TI  - Multi-objective evolutionary optimization for constructing neural networks for
      virtual reality visual data mining: application to geophysical prospecting.
AB  - A method for the construction of virtual reality spaces for visual data mining
      using multi-objective optimization with genetic algorithms on nonlinear
      discriminant (NDA) neural networks is presented. Two neural network layers (the
      output and the last hidden) are used for the construction of simultaneous
      solutions for: (i) a supervised classification of data patterns and (ii) an
      unsupervised similarity structure preservation between the original data matrix
      and its image in the new space. A set of spaces are constructed from selected
      solutions along the Pareto front. This strategy represents a conceptual
      improvement over spaces computed by single-objective optimization. In addition,
      genetic programming (in particular gene expression programming) is used for
      finding analytic representations of the complex mappings generating the spaces (a
      composition of NDA and orthogonal principal components). The presented approach
      is domain independent and is illustrated via application to the geophysical
      prospecting of caves.

PMID- 17532611
TI  - Role of reactive oxygen species in protein degradation in murine myotubes induced
      by proteolysis-inducing factor and angiotensin II.
AB  - The antioxidants butylated hydroxytoluene (BHT, 1 mM) and D-alpha-tocopherol (10
      microM) completely attenuated protein degradation in murine myotubes in response
      to both proteolysis-inducing factor (PIF) and angiotensin II (Ang II), suggesting
      that the formation of reactive oxygen species (ROS) plays an important role in
      this process. Both PIF and Ang II induced a rapid and transient increase in ROS
      formation in myotubes, which followed a parabolic dose-response curve, similar to
      that for total protein degradation. Antioxidant treatment attenuated the increase
      in expression and activity of the ubiquitin-proteasome proteolytic pathway by PIF
      and Ang II, by preventing the activation of the transcription factor nuclear
      factor-kappaB (NF-kappaB), through inhibition of phosphorylation of the NF-kappaB
      inhibitor protein (I-kappaB) and its subsequent degradation. ROS formation by
      both PIF and Ang II was attenuated by diphenyleneiodonium (10 microM), suggesting
      that it was mediated through the NADPH oxidase system. ROS formation was also
      attenuated by trifluoroacetyl arachidonic acid (10 microM), a specific inhibitor
      of cytosolic phospholipase A2, U-73122 (5 microM) and D609 (200 microM),
      inhibitors of phospholipase C and calphostin C (300 nM), a highly specific
      inhibitor of protein kinase C (PKC), all known activators of NADPH oxidase.
      Myotubes containing a dominant-negative mutant of PKC did not show an increase in
      ROS formation in response to either PIF or Ang II. The two Rac1 inhibitors W56
      (200 microM) and NSC23766 (10 microM) also attenuated both ROS formation and
      protein degradation induced by both PIF and Ang II. Rac1 is known to mediate
      signalling between the phosphatidylinositol-3 kinase (PI-3K) product and NADPH
      oxidase, and treatment with LY24002 (10 microM), a highly selective inhibitor of
      PI-3K, completely attenuated ROS production in response to both PIF and Ang II,
      and inhibited total protein degradation, while the inactive analogue LY303511
      (100 microM) had no effect. ROS formation appears to be important in muscle
      atrophy in cancer cachexia, since treatment of weight losing mice bearing the
      MAC16 tumour with D-alpha-tocopherol (1 mg kg(-1)) attenuated protein degradation
      and increased protein synthesis in skeletal muscle.

PMID- 17532612
TI  - Electric field and vibration-assisted nanomolecule desorption and anti-biofouling
      for biosensor applications.
AB  - A novel anti-fouling mechanism based on the combined effects of electric field
      and shear stress is reported. A lead zirconate titanate (PZT) composite is used
      to generate an electric field and an acoustic streaming shear stress that
      increase nanomolecule desorption. In vitro characterization showed that (1) 58+/
      5.5% and 39+/-5.2% of adsorbed bovine serum albumin (BSA) proteins can be
      effectively removed from fired silver and titanium coated PZT plate,
      respectively; and (2) 43+/-9.7% of the anti-mouse immunoglobulin G (IgG) can be
      effectively removed from a fired silver coated PZT plate. Theoretical
      calculations on protein-surface interactions (van der Waals (VDW), electrostatic,
      and hydrophobic) and shear stress describe the mechanism for protein desorption
      from model surfaces. We have shown that the applied electric potential is the
      major contributor in reducing the adhesive force between protein and surface, and
      the desorbed protein is taken away by acoustic streaming shear stress. We
      strongly believe that the present method offers the possibility of minimizing
      nanomolecule adsorption without further surface treatment.

PMID- 17532613
TI  - Synthesis of alpha-chymotrypsin/polymer composites by a reverse micelle/gas
      antisolvent method.
AB  - Alpha-chymotrypsin (CT)/polyvinylpyrrolidone (PVP) composites was synthesized by
      combination of reverse micelles and CO(2). In this method, the two reverse
      micellar solutions containing CT and PVP, respectively, were first mixed, then
      compressed CO(2) was used as an antisolvent to precipitate the CT and PVP
      simultaneously and CT/PVP composites were successfully prepared. The morphology
      of the obtained CT/PVP composites was characterized by transmission electron
      microscopy (TEM). The FTIR spectra of the composites showed that there was
      interaction between CT and PVP. The storage activity of the enzyme immobilized on
      the polymer by this method was higher than that of the pure enzyme. This method
      has some advantages and can be easily applied to the synthesis of some other
      enzyme/polymer composites.

PMID- 17532614
TI  - [Longitudinal evaluation of pulmonary function tests in children with newborn
      screening for cystic fibrosis. Relationships with pulmonary infection. Study of
      40 children undergoing 744 pulmonary function tests].
AB  - OBJECTIVES: To report longitudinal assessment of pulmonary function in children
      with neonatal screening for cystic fibrosis and its relationships with
      Pseudomonas aeruginosa (PA) chronic infection, nutritional status, sex, age and
      genotype. POPULATION AND METHODS: Children benefited systematically of 3 visits a
      year with pulmonary function tests (PFT) and bacteriological examination. Forty
      children and 744 PFTs were analysed, with 38 children during at least 4 years.
      RESULTS: We reported a decrease of pulmonary function tests with chronic PA
      infection and the genotype DeltaF508/DeltaF508. The decline was gradual and not
      different between not infected and recently infected children. The PFTs of
      children infected for a long times were very deteriorate, probably due to the
      fact that they were infected with multiresistant strains of PA. CONCLUSION: We
      think that it is important to survey pulmonary function before 5 years old in
      these early infected children. We should determinate if the important decrease of
      PFT in these early infected children is due to infection by PA mucoid.

PMID- 17532615
TI  - Higher-level phylogeny of Foraminifera inferred from the RNA polymerase II (RPB1)
      gene.
AB  - Macroevolutionary relations among main lineages of Foraminifera have
      traditionally been inferred from the small subunit ribosomal genes (SSU rDNA).
      However, important discrepancies in the rates of SSU rDNA evolution between major
      lineages led to difficulties in accurate interpretation of SSU-based phylogenetic
      reconstructions. Recently, actin and beta-tubulin sequences have been used as
      alternative markers of foraminiferal phylogeny and their analyses globally
      confirm results obtained with SSU rDNA. In order to test new protein markers, we
      sequenced a fragment of the largest subunit of the RNA polymerase II (RPB1), a
      nuclear encoded single copy gene, for 8 foraminiferal species representing major
      orders of Foraminifera. Analyses of our data robustly confirm previous SSU rDNA
      and actin phylogenies and show (i) the paraphyly and ancestral position of
      monothalamid Foraminifera; (ii) the independent origin of miliolids; (iii) the
      monophyly of rotaliids, including buliminids and globigerinids; and (iv) the
      polyphyly of planktonic families Globigerinidae and Candeinidae. Additionally,
      the RPB1 phylogeny suggests Allogromiidae as the most ancestral foraminiferal
      lineage. In the light of our study, RPB1 appears as a valuable phylogenetic
      marker, particularly useful for groups of protists showing extreme variations of
      evolutionary rates in ribosomal genes.

PMID- 17532617
TI  - Closed cycle construction: an integrated process for the separation and reuse of
      C&D waste.
AB  - In The Netherlands, construction and demolition (C&D) waste is already to a large
      extent being reused, especially the stony fraction, which is crushed and reused
      as a road base material. In order to increase the percentage of reuse of the
      total C&D waste flow to even higher levels, a new concept has been developed. In
      this concept, called 'Closed Cycle Construction', the processed materials are
      being reused at a higher quality level and the quantity of waste that has to be
      disposed of is minimised. For concrete and masonry, the new concept implies that
      the material cycle will be completely closed, and the original constituents (clay
      bricks, gravel, sand, cement stone) are recovered in thermal processes. The mixed
      C&D waste streams are separated and decontaminated. For this purpose several dry
      separation techniques are being developed. The quality of the stony fraction is
      improved so much, that this fraction can be reused as an aggregate in concrete.
      The new concept has several benefits from a sustainability point of view, namely
      less energy consumption, less carbon dioxide emission, less waste production and
      less land use (for excavation and disposal sites). One of the most remarkable
      benefits of the new concept is that the thermal process steps are fuelled with
      the combustible fraction of the C&D waste itself. Economically the new process is
      more or less comparable with the current way of processing C&D waste. On the
      basis of the positive results of a feasibility study, currently a pilot and
      demonstration project is being carried out. The aim is to optimise the different
      process steps of the Closed Cycle Construction process on a laboratory scale, and
      then to verify them on a large scale. The results of the project are promising,
      so far.

PMID- 17532618
TI  - A sensor for superoxide in aqueous and organic/aqueous media based on immobilized
      cytochrome c on binary self-assembled monolayers.
AB  - A method for the electrochemical detection of superoxide radical was developed,
      based on cytochrome c (cyt c) immobilized on the binary self-assembled monolayers
      (SAMs) of thioctic acid (T-COOH) and thioctic amide (T-NH2) on gold electrode.
      The sensor works by electrochemically detecting cyt c reduced by the superoxide
      radical generated by a xanthine-XOD system. The electrochemical properties of
      immobilized cyt c were investigated in aqueous buffer and in a mixture of aqueous
      and organic solvents. The interaction of superoxide radical with the modified
      electrode was characterized in phosphate buffer solution (PBS) and in the
      mixtures of both PBS and dimethyl sulfoxide (DMSO) and PBS and glycerol (Gly).
      The results showed that the sensors responded immediately to superoxide radical
      in PBS and gave a steady-state anodic current within 10s during the generation of
      superoxide radical. In 40% DMSO and in 30% Gly solution, the current response
      reached a steady-state anodic current within 20s. The sensor could also be used
      to estimate superoxide dismutase (SOD).

PMID- 17532619
TI  - Rapid, femtomolar bioassays in complex matrices combining microfluidics and
      magnetoelectronics.
AB  - A significant challenge for all biosensor systems is to achieve high assay
      sensitivity and specificity while minimizing sample preparation requirements,
      operational complexity, and sample-to-answer time. We have achieved multiplexed,
      unamplified, femtomolar detection of both DNA and proteins in complex matrices
      (including whole blood, serum, plasma, and milk) in minutes using as few as two
      reagents by labeling conventional assay schemes with micrometer-scale magnetic
      beads, and applying fluidic force discrimination (FFD). In FFD assays, analytes
      captured onto a microarray surface are labeled with microbeads, and a controlled
      laminar flow is then used to apply microfluidic forces sufficient to
      preferentially remove only nonspecifically bound bead labels. The density of
      beads that remain bound is proportional to the analyte concentration and can be
      determined with either optical counting or magnetoelectronic detection of the
      magnetic labels. Combining FFD assays with chip-based magnetoelectronic detection
      enables a simple, potentially handheld, platform capable of both nucleic acid
      hybridization assays and immunoassays, including orthogonal detection and
      identification of bacterial and viral pathogens, and therefore suitable for a
      wide range of biosensing applications.

PMID- 17532620
TI  - A nested case-control study of stomach cancer and serum insulin-like growth
      factor (IGF)-1, IGF-2 and IGF-binding protein (IGFBP)-3.
AB  - We conducted this study to investigate the association between serum levels of
      insulin-like growth factor (IGF)-1, IGF-2, and IGF-binding protein (IGFBP)-3 and
      the incidence of stomach cancer. A nested case-control study of 161 stomach
      cancer incidences and 314 matched controls was established within the Japan
      Collaborative Cohort Study. The adjusted ORs for IGF-1 quartile ranged from 0.84
      and 1.13, but these were not statistically significant. Further, higher IGF-2
      levels did not significantly correlate with the incidence of stomach cancer. A
      tendency for the risk of stomach cancer to decrease with increasing IGFBP-3 level
      was observed, but without statistical significance. A slight decrease in risk was
      seen with an increase in IGFBP-3 level, but neither change was statistically
      significant. To conclude, we found no association between IGF-1, IGF-2, or IGFBP
      3 serum levels and the risk of stomach cancer. As this association has not been
      established, these findings need to be confirmed in future studies.

PMID- 17532621
TI  - Clinical implications of steroid receptor coactivator (SRC)-3 in uterine
      endometrial cancers.
AB  - Estrogen is recognized as a significant modifier in the development, growth and
      invasion of uterine endometrial cancer. Steroid receptor coactivator-3 (SRC-3;
      AIB1, ACTR, RAC3, TRAM-1, and pCIP) is a member of the p160 family of coactivator
      for nuclear hormone receptors including estrogen receptor (ER). It is reported
      that SRC-3 is overexpressed in various cancers. However, SRC-3 expression manner
      in uterine endometrial cancer is not fully understood. In this study, we showed
      SRC-3 mRNA expression correlates with clinical stage, depth of myometrial
      invasion and dedifferentiation. The prognosis of the 25 patients with higher
      expression of SRC-3 mRNA in uterine endometrial cancers was extremely poor (36%),
      whereas the 24-month survival rate of the 15 patients with lower expression of
      SRC-3 mRNA was 96%. These data indicate that SRC-3 might be an important
      indicator of uterine endometrial cancer advancement and survival.

PMID- 17532622
TI  - Modern multimodality approach to hepatic colorectal metastases: solutions and
      controversies.
AB  - Hepatic resection for colorectal metastases, limited to the liver, has become the
      standard of care, and currently remains the only potentially curative therapy.
      Numerous single institutional reports have demonstrated long-term survival and
      there are no other treatment options that have shown a survival plateau. However,
      curative resection is possible in less than 25% of those patients with disease
      limited to the liver, which translates into only 5-10% of the original group
      developing colorectal cancer. To increase the number of patients who could
      benefit from hepatic resection, the last decade has seen considerable effort
      being directed towards novel approaches to permit curative hepatic resection such
      as: neoadjuvant systemic and regional chemotherapy, pre-operative portal vein
      embolization for hypertrophy of future liver remnant, staged hepatic resection
      and radio frequency ablation combined with resection for addressing multiple
      bilobar metastases. This article reviews development of these innovative
      multidisciplinary modalities and the aggressive surgical approach that has been
      adopted to extend the frontiers of surgical therapy for colorectal hepatic
      metastases.

PMID- 17532623
TI  - Kinetic sorption modelling of Cu, Ni, Zn, Pb and Cr ions to pine bark and blast
      furnace slag by using batch experiments.
AB  - Storm water and landfill leachate can both contain significant amounts of toxic
      metals such as Zn, Cu, Pb, Cr and Ni. Pine bark and blast furnace slag are both
      residual waste products that have shown a large potential for metal removal from
      contaminated water. There are however many variables that must be optimized in
      order to achieve efficient metal retention. One of these variables is the time of
      which the solution is in contact with each unit of filter material. Metal
      sorption was studied in two laboratory experiments to improve the knowledge of
      the effects of contact time. The results showed that pine bark was generally more
      efficient than blast furnace slag when the metal concentrations were relatively
      small, whereas blast furnace slag sorbed most metals to a larger extent at
      increased metal loads. In addition, sorption to blast furnace slag was found to
      be faster than metal binding to pine bark. A pseudo-second-order kinetic model
      was able to describe the data well within 1000 s of reaction time.

PMID- 17532624
TI  - Ozone treatment of process water from a dry-mill ethanol plant.
AB  - Fuel ethanol production in corn dry milling plants is a rapidly expanding
      industrial sector. Whole stillage, the residue from the distillation of the
      fermented corn, is centrifuged and the concentrate, thin stillage, is found to
      have a chemical oxygen demand (COD) of approximately 75,000 mg/L. This thin
      stillage is partly recycled, but much of it needs to be evaporated to concentrate
      the solubles for addition to the animal feed coproduct from corn dry milling.
      This research is an exploration into lowering COD from thin stillage using
      ozonation as a simple single-step unit process to facilitate a larger reusable
      fraction. The ozonation would usually be a pretreatment before additional
      flocculation or biological treatment. Also, COD removal by ozonation with and
      without a catalyst has been studied. Three different application rates of ozone
      O(3,1)=7 mg/min, O(3,2)=21 mg/min, and O(3,3)=33 mg/min were used for 8h into
      samples of 2L each of three dilutions 20x, 30x and 40x. COD removal of 85% was
      observed with an ozone dosage of 4000 mg/L into a 40x-diluted sample. This would
      correspond to about 0.5 mg COD removed per mg ozone dosed. However, at lower
      dosages and smaller dilutions, more than 1mg COD removal was achieved per mg
      ozone dosed. Two different catalysts, Fe(II) and Fe(III), were used and the
      samples were ozonated for 4 h. Five different dosages of each of the two
      catalysts were used and better COD removal was observed compared to ozonation
      alone with all 5 dosages. COD removal rate was increased from 45% to 74% with
      Fe(III) and was increased to 77% with Fe(II). Up to 10mg/L COD was removed per mg
      O(3) dosed well below the maximum dosage. Both the catalysts resulted in almost
      the same improved COD removal rates when compared to ozonation alone.

PMID- 17532625
TI  - Effects of cycle-frequency and temperature on the performance of anaerobic
      sequencing batch reactors (ASBRs) treating swine waste.
AB  - Anaerobic digestion of animal waste is a technically viable process for the
      abatement of adverse environmental impacts caused by animal wastes; however,
      widespread acceptance has been plagued by poor economics. This situation is
      dismal if the technology is adapted for treating low strength animal slurries
      because of large digester-volume requirements and a corresponding high energy
      input. A possible technology to address these constraints is the anaerobic
      sequencing batch reactor (ASBR). The ASBR technology has demonstrated remarkable
      potential to improve the economics of treating dilute animal waste effluents.
      This paper presents preliminary data on the effects of temperature and frequency
      cycle on the operation of an ASBR at a fixed hydraulic retention time (HRT). The
      results suggest that within the parameter range under consideration, temperature
      did not affect the biogas yield significantly, however, higher cycle-frequency
      had a negative effect. The biogas quality (%CH(4)) was not significantly affected
      by temperature nor by the cycle-frequency. The operating principle of the ASBR
      follows four phases: feed, react, settle, and decant in a cyclic mode. To improve
      the biogas production in an ASBR, one long react-phase was preferable compared to
      three shorter react-phases. Treatment of dilute manure slurries in an ASBR at 20
      degrees C was more effective than at 35 degrees C; similarly more bio-stable
      effluents were obtained at low cycle-frequency. The treatment of dilute swine
      slurries in an ASBR at the lower temperature (20 degrees C) and lower cycle
      frequency is, therefore, recommended for the bio-stabilization of dilute swine
      wastewaters. The results also indicate that significantly higher VFA degradation
      occurred at 20 degrees C than at 35 degrees C, suggesting that the treatment of
      dilute swine slurries in ASBRs for odor control might be more favorable at the
      lower than at the higher temperatures examined in this study. Volatile fatty acid
      reduction at the two reactor temperatures and cycle-frequencies, from a high of
      639+/-75 mg/L to a low of 92+/-23 mg/L, greatly reduced the odor and the odor
      generation potential in post-treatment storage. The nutrients (both N and P) in
      the waste influent were conserved in the effluents.

PMID- 17532626
TI  - Economical succinic acid production from cane molasses by Actinobacillus
      succinogenes.
AB  - In this work, production of succinic acid by Actinobacillus succinogenes
      CGMCC1593 using cane molasses as a low cost carbon source was developed. In
      anaerobic bottles fermentation, succinic acid concentration of 50.6+/-0.9 g l(-1)
      was attained at 60 h using an optimum medium containing molasses pretreated with
      sulfuric acid, resulting in a succinic acid yield of 79.5+/-1.1% and sugar
      utilization of 97.1+/-0.6%. When batch fermentation was carried out in a 5-l
      stirred bioreactor with pretreated molasses, 46.4 g l(-1) of succinic acid was
      attained at 48 h and faster cells growth was also observed. Fed batch
      fermentation was performed to minimize the substrate (sugar) inhibition effect,
      giving 55.2 g l(-1) of succinic acid and 1.15 g l(-1)h(-1) of productivity at 48
      h. The present study suggests that the inexpensive cane molasses could be
      utilized for the economical and efficient production of succinic acid by A.
      succinogenes.

PMID- 17532627
TI  - Isolation of a starch utilizing, phosphate solubilizing fungus on buffered medium
      and its characterization.
AB  - A phosphate solubilizing fungus, Paecilomyces marquandii AA1 was isolated from
      phosphate deficient soil on Pikovskaya's medium buffered with Tris-HCl pH 8. The
      organism was identified on the basis of morphological characterization and by
      sequencing of 18S rRNA gene. The organism could release phosphate from both
      buffered and unbuffered medium and solubilized rock phosphates from various
      places. The effect of concentration of ore, temperature, carbon and nitrogen
      sources on solubilization of rock phosphate was studied. Ammonium salts were the
      best nitrogen source, followed by asparagine, sodium nitrate, potassium nitrate,
      urea and calcium nitrate in that order.

PMID- 17532628
TI  - Pseudomonas aeruginosa immobilized multiwalled carbon nanotubes as biosorbent for
      heavy metal ions.
AB  - Pseudomonas aeruginosa immobilized multiwalled carbon nanotubes has been used as
      biosorbent for the solid phase extraction of some heavy metal ions in
      environmental samples. Cobalt(II), cadmium(II), lead(II), manganese(II),
      chromium(III) and nickel(II) ions have been selected as analytes for the
      presented study, due to their important negative and positive roles in human
      life. In order to investigate quantitative biosorption conditions of the
      analytes, the influences of pH of the aqueous solution, eluent type, eluent
      volume, samples volume, etc. were examined. The effects of alkaline, earth
      alkaline and some transitions metals on the biosorption of analyte ions on P.
      aeruginosa immobilized multiwalled carbon nanotubes were also investigated. The
      presented biosorption procedure was applied to the determination of analytes in
      tomato leaves, bovine liver, boiled wheat, canned fish, black tea, lichen and
      natural water samples.

PMID- 17532629
TI  - A new analytical approach to optimizing the design of large-scale composting
      systems.
AB  - This paper proposes a new approach on aiding for optimizing the design,
      operations, and maintenance planning of new and existing large-scale composting
      facilities. Numerical modeling on mass/energy transport, degradation process, and
      turning/shifting processes was discussed. The models are integrated with the 3D
      finite element method based system, which is able to solve for mass/energy
      distribution fields influenced by biological activities at each corresponding
      location and interaction with arbitrary environment. As a result, designing and
      planning for more cost-effective and better performance facilities without
      performing trail tests shall become possible.

PMID- 17532630
TI  - Design, synthesis, and biological activity of folate receptor-targeted prodrugs
      of thiolate histone deacetylase inhibitors.
AB  - Aiming to develop selective anticancer drugs, we designed and synthesized three
      disulfides bearing a folic acid moiety as candidate folate receptor (FR)-targeted
      prodrugs of thiolate histone deacetylase inhibitors. Among them, compound 1
      displayed growth-inhibitory activity toward folate receptor-positive MCF-7 breast
      cancer cells. The activity of 1 was significantly reduced by free folic acid,
      suggesting that cellular uptake of 1 is mediated by FR.

PMID- 17532632
TI  - The role of molecular size in ligand efficiency.
AB  - Ligand efficiency is a simple metric for assessing whether a ligand derives its
      potency from optimal fit with the protein target or simply by virtue of making
      many contacts. Comparison of protein-ligand binding affinities for over 8000
      ligands with 28 protein targets shows conclusively that the average ligand
      binding affinities are not linear with molecular size. It is therefore important
      to scale ligand efficiencies by the size of the ligand, particularly where small
      ligands (e.g., fragments) are involved. We propose a simple 'fit quality' metric
      that removes this dependence.

PMID- 17532633
TI  - Pyrazolone methylamino piperidine derivatives as novel CCR3 antagonists.
AB  - The discovery and optimization of a novel class of potent CCR3 antagonists is
      described. Details of synthesis and SAR are given together with some ADME
      properties of selected compounds. An optimal balance between activities,
      physicochemical properties, and in vitro metabolic stability was reached by the
      proper choice of substituents.

PMID- 17532631
TI  - Synthesis and evaluation of pyrazolo[3,4-b]pyridine CDK1 inhibitors as anti-tumor
      agents.
AB  - A series of 3,5-disubstituted pyrazolo[3,4-b]pyridine cyclin-dependent kinase
      (CDK) inhibitors was synthesized. These compounds showed potent and selective CDK
      inhibitory activities and inhibited in vitro cellular proliferation in cultured
      human tumor cells. Selected compounds were evaluated in an in vivo tumor
      xenograft model. The synthesis and biological evaluation of these pyrazolo[3,4
      b]pyridines and related compounds are reported.

PMID- 17532634
TI  - Synthesis and in vitro protozoocidal activity of diazabicyclic benzotropolone
      derivatives.
AB  - We describe the synthesis and protozoocidal evaluation of a series of
      diazabicycles based on benzotropolone ethers. Several of the compounds, which can
      be obtained through a high-yielding hetero Diels-Alder reaction using simple and
      readily available starting materials, have in vitro activities against
      Trypanosoma cruzi and Leishmania donovani that are comparable to, and in some
      cases better than, those of currently used chemotherapies.

PMID- 17532635
TI  - The effects of a concurrent cognitive task on the postural control of young
      children with and without developmental coordination disorder.
AB  - The purpose of this study was to examine how dual-task performance affects the
      center of pressure (COP) sway characteristics and cognitive performance of
      children with developmental coordination disorder (DCD). Twenty-six children with
      DCD (mean age-5.1+/-0.59 years) and 20 typically developing children (mean age
      5.0+/-0.57 years) participated in the study. The postural task consisted of
      standing quietly either on a firm or a compliant surface. The cognitive task
      involved naming simple objects appearing consecutively on a computer screen. Five
      tests were presented in random order, with the cognitive and the postural tasks
      tested either separately or concurrently. Mistakes in naming the objects were
      recorded, as were COP sway characteristics measured with a force-plate. Children
      with DCD demonstrated higher COP path-length velocity (PLV), and COP amplitude
      variability, as well as more mistakes in naming the objects in all stance
      conditions. A concurrent cognitive task increased all sway measures in both
      groups, with the effect on PLV greater in children with DCD. Cognitive
      performance was affected by dual tasking only in the control group. Young
      children with DCD demonstrated greater postural control activity than did the
      children in the control group during quiet stance, whether performed as a single
      or a dual task. This difference is accentuated during dual tasking when the
      children with DCD seem to prioritize the cognitive task.

PMID- 17532636
TI  - The association between impaired turning and normal straight walking in
      Parkinson's disease.
AB  - Turning whilst walking was investigated by gait analysis in a group of
      Parkinson's Disease (PD) patients with mild clinical impairment and no
      significant abnormalities in stride parameters and kinematics of steady-state,
      linear walking. Comparison with age-matched controls demonstrated that patients
      approached turns with a slower step and completed turning with a greater number
      of steps. Moreover, the normal cranio-caudal sequence, whereby rotation of the
      head toward the intended direction of travel is followed by rotation of the
      trunk, was replaced by nearly simultaneous rotation of head and trunk and
      decreased relative head excursion after the second turning step. The evidence of
      abnormal inter-segmental coordination during turning in mildly affected, normally
      walking patients suggests that task-specific pathophysiological mechanisms, not
      necessary related to basic locomotor deficits, underlie disturbed directional
      changes in PD. Furthermore, turning-related neural systems may be more vulnerable
      to functional impairments associated with PD, as compared with linear walking.
      Hierarchically higher control levels involved in the turning ability may explain
      the observed unexpected association.

PMID- 17532637
TI  - The biomechanics of step descent under different treatment modalities used in
      patellofemoral pain.
AB  - BACKGROUND: Most previous work on the use of knee bracing and taping has focussed
      on sagittal plane movement. However, most bracing and taping techniques aim to
      modify patellar movement in the coronal and transverse planes. OBJECTIVE: This
      study investigated the effect of patellar bracing and taping on the three
      dimensional mechanics of the knee during a controlled eccentric step down task.
      METHOD: Twelve healthy subjects were asked to conduct a slow step down exercise.
      The step down was conducted under three randomised conditions: (a) no
      intervention, (b) neutral patella taping and (c) patellofemoral bracing. A step
      was constructed to accommodate an AMTI force platform and to produce a step
      height of 20 cm. Kinematic data were collected using a six camera ProReflex
      motion analysis system. Reflective markers were placed on the foot, shank and
      thigh using the Calibrated Anatomical Systems Technique (CAST). RESULTS: The
      patellofemoral brace and taping led to a significant reduction in the maximum
      coronal and range of torsional knee angles by 5 degrees and 2 degrees ,
      respectively (p=0.030, 0.006). The range of coronal and transverse plane knee
      moments was also significantly reduced by 0.15 Nm/kg and 0.03 Nm/kg (p=0.020,
      0.0019). The brace was shown to be more effective in the coronal and transverse
      planes in comparison to taping or no intervention. CONCLUSION: Bracing and taping
      appear to offer coronal plane and torsional control of the knee during eccentric
      step descent. Coronal and transverse plane mechanics should not be overlooked
      when studying patellofemoral pain.

PMID- 17532638
TI  - Development of walking in preterm and term infants: age of onset, qualitative
      features and sensitivity to resonance.
AB  - An increasing number of studies have examined the development of walking in
      preterm infants; however, the results concerning those who had no major neonatal
      disease were inconclusive. This study was therefore aimed to examine the age of
      onset, the quality of early walking movement, and the sensitivity to resonant
      period of the force-driven harmonic oscillator (FDHO) model in preterm infants
      who had no major neonatal disease and normal term infants. Twenty-nine preterm
      infants and 29 term infants were prospectively examined for their age of onset of
      independent walking and were subsequently assessed the qualitative features of
      walking at 18 months of corrected age using kinematic analysis. Kinematic
      variables examined included spatio-temporal organization, inter-joint
      coordination, and inter-limb coordination. The anthropometric data were used to
      calculate the resonant period. The results demonstrated that the preterm infants
      attained independent walking at significantly older ages than the term infants
      when corrected for prematurity. The preterm infants manifested similar walking
      characteristics, except for shorter stride lengths, at 18 months of corrected age
      compared with the term infants. Furthermore, the stride periods of both groups
      were accurately predicted by the resonant period of the FDHO model. We conclude
      that preterm birth without accompanied major neonatal disease may affect infants'
      age of onset and spatial organization but not their sensitivity to resonance
      during the early stage of walking development.

PMID- 17532639
TI  - Synthesis, antifungal and antimicrobial activity of alkylphospholipids.
AB  - The antifungal, antibacterial and haemolytic activity of a series of
      alkylphosphocholines (e.g., miltefosine) and alkylglycerophosphocholines (e.g.,
      edelfosine) has been investigated. These compound classes exhibit significant
      antifungal and moderate antibacterial activities. Several new alkylphosphocholine
      derivatives with amide or ester bonds in the alkyl chain have been synthesised.
      These compounds show much lower haemolytic activity than miltefosine.
      Alkylphosphocholines and alkylglycerophosphocholines show significant promise as
      novel orally available antifungal and antibacterial therapeutics.

PMID- 17532640
TI  - Molecular design, chemical synthesis, and biological evaluation of '4-1'
      pentacyclic aryl/heteroaryl-imidazonaphthalimides.
AB  - A novel series of '4-1' pentacyclic naphthalimides, where the chromophore
      consists of a naphthalimide moiety, fused to an imidazole ring containing an
      unfused aryl or heteroaryl ring, were synthesized and evaluated for in vitro
      antitumor activity. In general, the new derivatives showed an improved cytotoxic
      activity over amonafide. DNA binding experiments supported that this class of
      compounds behaves as effective DNA-intercalating agents.

PMID- 17532641
TI  - Design, synthesis, and evaluation of potent, structurally novel peroxisome
      proliferator-activated receptor (PPAR) delta-selective agonists.
AB  - A series of 3-(4-alkoxyphenyl)propanoic acid derivatives was prepared as
      candidate peroxisome proliferator-activated receptor (PPAR) delta-selective
      agonists, based on our previously discovered potent human PPARalpha/delta dual
      agonist TIPP-401 as a lead compound. Structure-activity relationship studies
      clearly indicated the importance of the chain length of the alkoxy group at the 4
      position, and the n-butoxy compound exhibited the most potent PPARdelta
      transactivation activity and highest PPARdelta selectivity. The (S)-enantiomer of
      a representative compound exhibited extremely potent PPARdelta transactivation
      activity, comparable with or somewhat superior to that of the known PPARdelta
      selective agonist, GW-501516. The representative compound regulated the
      expression of genes involved in lipid and glucose homeostasis, and should be
      useful not only as a chemical tool to study PPARdelta function, but also as a
      candidate drug for the treatment of metabolic syndrome.

PMID- 17532642
TI  - AAV2-mediated delivery of human neurturin to the rat nigrostriatal system: long
      term efficacy and tolerability of CERE-120 for Parkinson's disease.
AB  - Neurturin (NTN) is a neurotrophic factor with known potential to protect and
      restore the function of dopaminergic substantia nigra neurons whose degeneration
      has been most closely linked to the major motor deficits in Parkinson's disease
      (PD). CERE-120, an adeno-associated virus serotype 2 (AAV2)-based gene delivery
      vector encoding human NTN, is being developed as a potential therapeutic for PD.
      In a series of preclinical studies reported herein, CERE-120 delivery to the
      striatum produced a dose-related neuroprotection of nigrostriatal neurons in the
      rat 6-hydroxydopamine (6-OHDA) lesion model. Long-lasting efficacy of CERE-120
      was evidenced by substantia nigra cell protection, preserved fiber innervation of
      the striatum, and behavioral recovery for at least 6 months. In addition,
      striatal infusion of CERE-120 was found to have a safety and tolerability profile
      devoid of side effects or toxicological responses, for at least 12 months post
      treatment, even at dose multiples 125 times that of the lowest efficacious dose
      tested. These results support the ongoing CERE-120 clinical program in PD
      patients.

PMID- 17532644
TI  - Marlin-1 and conventional kinesin link GABAB receptors to the cytoskeleton and
      regulate receptor transport.
AB  - The cytoskeleton and cytoskeletal motors play a fundamental role in
      neurotransmitter receptor trafficking, but proteins that link GABA(B) receptors
      (GABA(B)Rs) to the cytoskeleton have not been described. We recently identified
      Marlin-1, a protein that interacts with GABA(B)R1. Here, we explore the
      association of GABA(B)Rs and Marlin-1 to the cytoskeleton using a combination of
      biochemistry, microscopy and live cell imaging. Our results indicate that Marlin
      1 is associated to microtubules and the molecular motor kinesin-I. We demonstrate
      that a fraction of Marlin-1 is mobile in dendrites of cultured hippocampal
      neurons and that mobility is microtubule-dependent. We also show that GABA(B)Rs
      interact robustly with kinesin-I and that intracellular membranes containing
      GABA(B)Rs are sensitive to treatments that disrupt a protein complex containing
      Marlin-1, kinesin-I and tubulin. Finally, we report that a kinesin-I mutant
      severely impairs receptor transport. We conclude that Marlin-1 and kinesin-1 link
      GABA(B)Rs to the tubulin cytoskeleton in neurons.

PMID- 17532643
TI  - Mecp2 deficiency leads to delayed maturation and altered gene expression in
      hippocampal neurons.
AB  - It is well known that Rett Syndrome, a severe postnatal childhood neurological
      disorder, is mostly caused by mutations in the MECP2 gene. However, how
      deficiencies in MeCP2 contribute to the neurological dysfunction of Rett Syndrome
      is not clear. We aimed to resolve the role of MeCP2 epigenetic regulation in
      postnatal brain development in an Mecp2-deficient mouse model. We found that,
      while Mecp2 was not critical for the production of immature neurons in the
      dentate gyrus (DG) of the hippocampus, the newly generated neurons exhibited
      pronounced deficits in neuronal maturation, including delayed transition into a
      more mature stage, altered expression of presynaptic proteins and reduced
      dendritic spine density. Furthermore, analysis of gene expression profiles of
      isolated DG granule neurons revealed abnormal expression levels of a number of
      genes previously shown to be important for synaptogenesis. Our studies suggest
      that MeCP2 plays a central role in neuronal maturation, which might be mediated
      through epigenetic control of expression pathways that are instrumental in both
      dendritic development and synaptogenesis.

PMID- 17532645
TI  - The association between mammographic breast density and bone mineral density in
      the study of women's health across the nation.
AB  - BACKGROUND: Bone mineral density and mammographic breast density are each
      associated with markers of lifetime estrogen exposure. The association between
      mammographic breast density and bone mineral density in early perimenopausal
      women is unknown. METHODS: We analyzed data from a cohort (n = 501) of
      premenopausal (no change in menstrual regularity) and early perimenopausal
      (decreased menstrual regularity in past 3 months) participants of African
      American, Caucasian, Chinese, and Japanese ethnicity in the Study of Women's
      Health Across the Nation. Using multivariable linear regression, we examined the
      cross-sectional association between percent mammographic density and bone mineral
      density (BMD). RESULTS: Percent mammographic density was statistically
      significantly inversely associated with hip BMD and lumbar spine BMD after
      adjustment (body mass index, ethnicity, age, study site, parity, alcohol intake,
      cigarette smoking, physical activity, age at first childbirth) in early
      perimenopausal, but not premenopausal, women. In early perimenopausal women,
      every 0.1g/cm(2) greater hip BMD predicted a 2% lower percent mammographic
      density (95% confidence interval -37.0 to -0.6%, p = 0.04). CONCLUSION:
      Mammographic breast density is inversely associated with BMD in the
      perimenopausal participants of this community-based cohort. The biological
      underpinnings of these findings may reflect differential responsiveness of breast
      and bone mineral density to the steroid milieu.

PMID- 17532646
TI  - On evaluating brain tissue classifiers without a ground truth.
AB  - In this paper, we present a set of techniques for the evaluation of brain tissue
      classifiers on a large data set of MR images of the head. Due to the difficulty
      of establishing a gold standard for this type of data, we focus our attention on
      methods which do not require a ground truth, but instead rely on a common
      agreement principle. Three different techniques are presented: the Williams'
      index, a measure of common agreement; STAPLE, an Expectation Maximization
      algorithm which simultaneously estimates performance parameters and constructs an
      estimated reference standard; and Multidimensional Scaling, a visualization
      technique to explore similarity data. We apply these different evaluation
      methodologies to a set of eleven different segmentation algorithms on forty MR
      images. We then validate our evaluation pipeline by building a ground truth based
      on human expert tracings. The evaluations with and without a ground truth are
      compared. Our findings show that comparing classifiers without a gold standard
      can provide a lot of interesting information. In particular, outliers can be
      easily detected, strongly consistent or highly variable techniques can be readily
      discriminated, and the overall similarity between different techniques can be
      assessed. On the other hand, we also find that some information present in the
      expert segmentations is not captured by the automatic classifiers, suggesting
      that common agreement alone may not be sufficient for a precise performance
      evaluation of brain tissue classifiers.

PMID- 17532647
TI  - The functional role of dorso-lateral premotor cortex during mental rotation: an
      event-related fMRI study separating cognitive processing steps using a novel task
      paradigm.
AB  - Subjects deciding whether two objects presented at angular disparity are
      identical or mirror versions of each other usually show response times that
      linearly increase with the angle between objects. This phenomenon has been termed
      mental rotation. While there is widespread agreement that parietal cortex plays a
      dominant role in mental rotation, reports concerning the involvement of motor
      areas are less consistent. From a theoretical point of view, activation in motor
      areas suggests that mental rotation relies upon visuo-motor rather than visuo
      spatial processing alone. However, the type of information that is processed by
      motor areas during mental rotation remains unclear. In this study we used event
      related fMRI to assess whether activation in parietal and dorsolateral premotor
      areas (dPM) during mental rotation is distinctively related to processing spatial
      orientation information. Using a newly developed task paradigm we explicitly
      separated the processing steps (encoding, mental rotation proper and object
      matching) required by mental rotation tasks and additionally modulated the amount
      of spatial orientation information that had to be processed. Our results show
      that activation in dPM during mental rotation is not strongly modulated by the
      processing of spatial orientation information, and that activation in dPM areas
      is strongest during mental rotation proper. The latter finding suggests that dPM
      is involved in more generalized processes such as visuo-spatial attention and
      movement anticipation. We propose that solving mental rotation tasks is heavily
      dependent upon visuo-motor processes and evokes neural processing that may be
      considered as an implicit simulation of actual object rotation.

PMID- 17532648
TI  - Localizing the rostrolateral prefrontal cortex at the individual level.
AB  - The functions of the rostrolateral prefrontal cortex (RLPFC) have recently become
      the target of multiple theories and empirical investigations. This region can be
      loosely defined as the lateral portion of Brodmann area (BA) 10. One of the
      challenges in testing theories about RLPFC functions is the difficulty in
      defining its boundaries when formulating predictions for its recruitment. Here we
      present a procedure that goes beyond the currently available anatomical
      definitions to attempt a functional localization of RLPFC. A combination of
      functional and anatomical criteria was employed, consistent with other localizer
      procedures. Functional localization was performed by comparing a relational
      condition involving relational matching to a control condition involving feature
      matching. It was expected that within an anatomically defined BA10 region, this
      procedure would produce functional activations in the lateral but not the medial
      subregions. The task was administered in the course of a single 13-min fMRI
      session. Results showed remarkable consistency, with all subjects activating
      RLPFC and activations consistently localized in the lateral part of BA10. These
      results demonstrate the practical feasibility of localizing RLPFC using a short
      procedure and a combination of functional and anatomical criteria. Such
      localization presents with a number of potential advantages for testing theories
      of RLPFC functions, including improved anatomical precision of experimental
      predictions, as well as the possibility of reduction in the rate of false
      negative findings across studies. In addition, the results provide further
      support for the previously proposed functional dissociation between lateral and
      medial BA10.

PMID- 17532650
TI  - Fruiting and non-fruiting myxobacteria: a phylogenetic perspective of cultured
      and uncultured members of this group.
AB  - The diversity of myxobacteria present in campus garden soil was surveyed by both
      cultivation-based and cultivation-independent methods. Detailed phylogenetic
      analysis of cultured and uncultured myxobacteria 16S rRNA gene sequences revealed
      that many undescribed relatives of the myxobacteria exist in nature. Molecular
      systematic analyses also revealed that myxobacterial genera described to date on
      the basis of the morphology of multi-cellular fruiting bodies were mostly
      monophyletic. However, these known taxa comprised only in a small part of the
      sequences recovered directly from soil in a cultivation-independent approach,
      indicating that the group is much more diverse than previously thought. We
      propose that the myxobacteria exist in two forms: the fruiting and the non
      fruiting types. Most of the uncultured myxobacteria may represent taxa which
      rarely form fruiting bodies, or may lack some or all of the developmental genes
      needed for fruiting body formation. In order to identify non-fruiting
      myxobacteria, new morphology-independent cultivation and isolation techniques
      need to be developed.

PMID- 17532649
TI  - Effects of diffusion weighting schemes on the reproducibility of DTI-derived
      fractional anisotropy, mean diffusivity, and principal eigenvector measurements
      at 1.5T.
AB  - Diffusion tensor imaging (DTI) is used to study tissue composition and
      architecture in vivo. To increase the signal to noise ratio (SNR) of DTI
      contrasts, studies typically use more than the minimum of 6 diffusion weighting
      (DW) directions or acquire repeated observations of the same set of DW
      directions. Simulation-based studies have sought to optimize DTI acquisitions and
      suggest that increasing the directional resolution of a DTI dataset (i.e., the
      number of distinct directions) is preferable to repeating observations, in an
      equal scan time comparison. However, it is not always clear how to translate
      these recommendations into practice when considering physiological noise and
      scanner stability. Furthermore, the effect of different DW schemes on in vivo DTI
      findings is not fully understood. This study characterizes how the makeup of a DW
      scheme, in terms of the number of directions, impacts the precision and accuracy
      of in vivo fractional anisotropy (FA), mean diffusivity (MD), and principal
      eigenvector (PEV) findings. Orientation dependence of DTI reliability is
      demonstrated in vivo and a principled theoretical framework is provided to
      support and interpret findings with simulation results. As long as sampling
      orientations are well balanced, differences in DTI contrasts due to different DW
      schemes are shown to be small relative to intra-session variability. These
      differences are accentuated at low SNR, while minimized at high SNR. This result
      suggests that typical clinical studies, which use similar protocols but different
      well-balanced DW schemes, are readily comparable within the experimental
      precision.

PMID- 17532651
TI  - Medical therapy for intermittent claudication.
AB  - Medical therapy to improve symptoms, stabilise the underlying vascular disease
      and improve lower limb outcomes is an important and effective adjunct to
      lifestyle modification and surgical or endovascular interventions in patients
      with IC. Randomised placebo controlled trials have shown that the
      phosphodiesterase III inhibitor cilostazol 100mg bid improves pain-free and
      maximum walking distance, as well as quality of life, in a range of patients with
      intermittent claudication in whom there is no evidence of tissue necrosis or rest
      pain. This review summarises the evidence from 8 pivotal trials of cilostazol
      involving over 2000 patients with intermittent claudication treated for up to 6
      months. There is comparatively less evidence to support the use of other
      treatment modalities for relief of symptoms in intermittent claudication, but
      there is considerable interest in therapeutic angiogenesis to promote new vessel
      formation and enhance collateralisation of the lower limb using recombinant
      growth factor proteins or gene transfer strategies. The rationale for therapeutic
      angiogenesis is discussed, together with the most recent results from randomised
      trials in patients with peripheral arterial disease.

PMID- 17532652
TI  - Trisomy of chromosome 21 in leukemogenesis.
AB  - Extra copies of chromosome 21 are often found in sporadic leukemias.
      Constitutional trisomy 21 of Down syndrome (DS) is associated with markedly
      increased risk for childhood leukemia. Thus the oncogenic role of trisomy 21 in
      the more common sporadic childhood leukemias may be revealed through the
      investigations of the relatively rare leukemias of DS. Recent studies of the
      megakaryoblastic leukemias of Down syndrome have uncovered a developmental
      leukemogenic mechanism characterized by a unique pre-natal collaboration between
      overexpressed genes from chromosome 21 and an acquired mutation in the
      transcription factor GATA1. The base of the markedly enhanced risk for acute
      lymphoblastic leukemia conferred by trisomy 21 is still unclear. Studies of the
      leukemias of DS are likely to contribute to the general understanding of the
      oncogenic mechanisms of chromosomal aneuploidies, the most common abnormalities
      in cancer.

PMID- 17532653
TI  - Ethanol-induced changes in expression profiles of cell growth, fatty acid and
      desaturase genes of Mucor rouxii.
AB  - We investigated the response of Mucor rouxii to ethanolic stress conditions. A
      differential response was found that was dependent on growth phase and ethanol
      concentration. 5% (v/v) ethanol showed an inhibitory effect on the mycelial
      growth of all stages. However, the ethanol sensitivity was specifically observed
      in active growing phases (12 and 21 h-grown cultures), in which the biomass and
      ratio of unsaturated/saturated fatty acids (UFA/SFA) decreased greatly after
      ethanol exposure compared to non-ethanol adding culture. With respect to
      different ethanol concentrations, M. rouxii was tolerant to low ethanol
      concentrations (about 1-3%, v/v) such that there was not much change in biomass
      and UFA/SFA ratio, in contrast to the 5% ethanol-added culture. We also showed
      the molecular basis of this response mechanism, demonstrating that expression of
      Delta(9)-, Delta(12)- and Delta(6)-desaturase genes, responsible for fatty acid
      desaturation in M. rouxii, were coordinately down-regulated upon exposure to
      ethanol stress.

PMID- 17532654
TI  - Computational alanine scanning and free energy decomposition for E. coli type I
      signal peptidase with lipopeptide inhibitor complex.
AB  - A thorough investigation of different roles of Escherichia coli type I signal
      peptidase residues binding to lipopeptide inhibitor has been performed by a
      combination of computational alanine scanning mutagenesis and free energy
      decomposition methods. PB and GB models are both used to evaluate the binding
      free energy in computational alanine scanning method and only GB model can be
      used to decompose the binding free energy on a per-residue basis. The regression
      analysis between the PB and GB model and also between the computational alanine
      scanning and free energy decomposition have been reported with a correlation
      coefficient of 0.96 and 0.83, respectively, which suggest they are both in fair
      agreement with each other. Moreover, the contribution components from van der
      Waals, electrostatic interaction, non-polar and polar energy of solvation, have
      been determined as well as the effects of backbones and side-chains. The results
      indicate that Lys145 is the most important residue for the binding but also acts
      as a general base, activating Ser90 to increase its nucleophility, recognizing
      and stabilizing the binding of lipopeptide inhibitor to the E. coli SPase. The
      hydroxyl group of Ser88 plays a key role for the binding of the inhibitor. Ser90
      contributes more to the intramolecular interaction than to the intermolecular
      interaction. Tyr143 and Phe84 contribute larger van der Waals interaction
      energies, indicating that these residues can be important for the selection based
      on the shape of the inhibitors. The contributions from other several interfacial
      residues of the E. coli SPase are also analyzed. This study can be a guide for
      the optimization of lipopeptide inhibitors and future design of new therapeutic
      agents for the treatment of bacterial infections.

PMID- 17532655
TI  - Seasonal variations in the intermediate metabolism of Parastacus varicosus
      (Crustacea, Decapoda, Parastacidae).
AB  - The aim of this study was to analyze the seasonal variations in the metabolism of
      Parastacus varicosus and examine the possible relationships to its reproduction.
      Animals were sampled (9 h to 10 h) in each month in the Gravatai River, RS,
      Brazil. Haemolymph samples were collected from each crayfish in the field for
      determination of glucose, total proteins, total lipids, and total cholesterol.
      Hepatopancreas, abdominal muscle, and gonads were removed for determination of
      glycogen, total proteins, total lipids, and total cholesterol. ANOVA revealed
      significant seasonal differences in the biochemical composition of all tissues
      studied; when the sexes were compared these parameters did not show any
      significant difference in the hepatopancreas and muscle. However, in haemolymph
      we observed significant variation only in cholesterol and lipid levels. The
      results suggest that the metabolic variability is related to the stage of
      maturation of the gonads, in females, where the hepatopancreas and other tissue
      studies can store and transfer reserves to support maturation to complement the
      food intake. Variations in the gonadosomatic and hepatosomatic indices suggest
      that reproduction occurs principally in summer. As in other decapods, abiotic
      factors such as water temperature, oxygen content, etc. influence the
      intermediate metabolism.

PMID- 17532656
TI  - Wrapped in subway logos, free city condom is a hit.

PMID- 17532657
TI  - Pivotal moments in HIV treatment: the 14th CROI.

PMID- 17532659
TI  - Costs of HIV care: evolution and update.

PMID- 17532658
TI  - Policy watch. Haven't we been here before?

PMID- 17532660
TI  - Images in HIV/AIDS. Pericardial primary effusion lymphoma.

PMID- 17532661
TI  - Uganda's early gains against HIV eroding.

PMID- 17532662
TI  - Assessing kidney function in HIV infection.
AB  - Chronic kidney disease often goes unrecognized, and the NIH encourages clinical
      laboratories to report glomerular filtration rate (GFR) estimates when they
      report serum creatinine levels. Chronic kidney disease based on estimated GFRs
      below 60 mL/min/1.73m2 is seen in as many as 10% of persons with HIV infection
      and even more frequently when urinary protein excretion is measured. The
      Cockcroft-Gault formula and Modification of Diet in Renal Disease (MDRD) equation
      are the most widely used to estimate GFR. Although which estimate is more
      reliable is still debated, both are superior to serum creatinine levels alone for
      evaluating kidney function. The Cockcroft-Gault formula is the standard FDA
      measure for recommended renal dose adjustment; the MDRD equation is considered
      the most reliable predictor of GFR within the range of 20 to 60 mL/min/1.73m2.
      Neither equation has been validated in HIV or other special populations. Patients
      with proteinuria or a reduced GFR should undergo further evaluation and referral
      to a nephrologist.

PMID- 17532663
TI  - Editorial comment: screening for chronic kidney disease requires creatinine
      references ranges not equations.

PMID- 17532665
TI  - Molecules in silico: a graph description of chemical reactions.
AB  - A general mathematical description, mostly in terms of graph theory, is given for
      reactions of organic chemistry. The corresponding computer program generates all
      products that can result from a given set of starting materials interacting
      according to a given set of reaction schemes. Example reactions from
      combinatorial chemistry, synthetic organic chemistry, and mass spectroscopic
      structure elucidation are considered in detail.

PMID- 17532664
TI  - Advances in HIV therapeutics: the 14th CROI.

PMID- 17532666
TI  - Taste comparisons for lansoprazole strawberry-flavoured delayed-release orally
      disintegrating tablet and ranitidine peppermint-flavoured syrup in children.
AB  - OBJECTIVE: To compare the flavour and taste preferences of two acid-inhibitory
      therapies in children. SUBJECTS AND SETTING: 104 (52 male and 52 female) healthy
      children aged 6-11 years participated in this phase IV single-centre, taste-test
      study after parental consent was obtained. METHODS: Children were divided into
      two groups based upon age: group 1 included children aged 6-8 years and group 2
      included children aged 9-11 years. Within each group an equal number of male and
      female subjects were recruited. Within each of the four strata defined by group
      and sex, an equal number of subjects were randomised to taste the strawberry
      flavoured lansoprazole 15mg orally disintegrating tablet or the ranitidine
      75mg/5mL peppermint-flavoured syrup samples in position 1. In group 1, the
      lansoprazole 15mg delayed-release orally disintegrating tablet was dispersed in
      5mL of water, while in group 2, children gently rolled the tablet on the tongue
      until dissolution, before swallowing the particles. Children given the dose of
      lansoprazole dispersed in water (group 1) and the ranitidine dose (groups 1 and
      2) were to taste it, swish it in their mouth for up to 10 seconds, and then
      swallow it. Children were given ambient temperature water and unsalted crackers
      to cleanse the palate during a 10-minute break between tastings. MAIN OUTCOME
      MEASURES: After each tasting, children rated their degree of liking on a five
      point facial hedonic scale (5 = like very much, 1 = dislike very much). Product
      preference was recorded after the tasting of both samples. RESULTS: Among group 1
      and group 2 participants, 86.5% (45/52) and 90.4% (47/52) of children,
      respectively, 'liked' ('like a little' or 'like very much') the strawberry
      flavoured lansoprazole orally disintegrating tablet. The proportion of children
      who 'liked' the peppermint-flavoured ranitidine syrup was lower than the
      proportion who liked lansoprazole, and the proportions were similar between the
      groups: 13.5% (7/52) in group 1 and 9.6% (5/52) in group 2. Children in both
      groups preferred the strawberry-flavoured lansoprazole delayed-release orally
      disintegrating tablet: 92% (95% CI 81.1, 97.8; p < 0.001) of those in group 1 and
      98% (95% CI 89.7, 100.0; p < 0.001) of those in group 2. CONCLUSION: After
      tasting both products, >92% of children aged from 6-11 years preferred the
      strawberry-flavoured lansoprazole delayed-release orally disintegrating tablet,
      either dissolved in a small amount of water or allowed to dissolve on the tongue,
      over the peppermint-flavoured ranitidine syrup.

PMID- 17532668
TI  - Further evidence for interethnic differences in the oral pharmacokinetics of
      meloxicam.
AB  - INTRODUCTION: Meloxicam is a nonsteroidal anti-inflammatory agent used widely in
      therapeutics. It is mainly metabolised by the cytochrome P450 enzyme (CYP) 2C9,
      with minor involvement of CYP3A4. So far, no information on the oral
      pharmacokinetics of this drug in adult Mexicans is available. The purpose of this
      study was to evaluate the oral pharmacokinetics of meloxicam in Mexican subjects.
      METHODS: Twenty-four healthy male subjects received an oral dose of meloxicam
      7.5mg after fasting for 10 hours. Blood samples were drawn from a suitable
      forearm vein and plasma obtained. The meloxicam concentration was evaluated by a
      high-performance liquid chromatographic method and pharmacokinetic parameters
      were obtained by non-compartmental techniques. Pharmacokinetic parameters
      obtained in this study were compared with those reported under similar conditions
      in other populations in order to establish if interethnic differences in the
      pharmacokinetics of meloxicam exist. RESULTS: After administration of meloxicam,
      plasma levels increased to a maximum concentration (C(max)) of 0.702 +/- 0.027
      (mean +/- SEM) microg/mL with a time to reach C(max) of 4.77 +/- 0.65h. The area
      under the plasma concentration versus time curve was 24.82 +/- 1.23 microg .
      h/mL. The clearance was about 4.8 mL/min and the volume of distribution 9.8 +/-
      0.36L. When these parameters were compared with those reported in German and
      Indian subjects, a reduced clearance and volume of distribution were evident in
      Mexicans. However, clearance and volume of distribution obtained in this study
      were very similar to those reported in Chinese subjects. CONCLUSIONS: The oral
      pharmacokinetic parameters of meloxicam in healthy Mexican subjects compared with
      historic controls reported in other populations showed a reduced clearance and
      volume of distribution when compared with German subjects, whereas no differences
      between Mexican and Chinese subjects were observed. These results suggest that
      there are interethnic differences in the pharmacokinetics of meloxicam.

PMID- 17532667
TI  - Efficacy of a Low-Dose Omeprazole-Based Triple-Therapy Regimen for Helicobacter
      pylori Eradication Independent of Cytochrome P450 Genotype : The Japanese MACH
      Study.
AB  - OBJECTIVES: To investigate the efficacies of two different triple-therapy
      regimens (standard versus low doses), and the influence of cytochrome P450 enzyme
      (CYP) genetic polymorphism on these efficacies, in Japanese patients undergoing
      Helicobacter pylori eradication treatment. METHODS: All patients received 1 week
      of triple therapy. Patients in group A (low-dose regimen) received omeprazole 40
      mg/day + amoxicillin 1500 mg/day + clarithromycin 800 mg/day; patients in group B
      (standard-dose regimen) received omeprazole 40 mg/day + amoxicillin 2000 mg/day +
      clarithromycin 1000 mg/day. RESULTS: A total of 225 patients (113 in group A and
      112 in group B) were randomised to one of the two triple-therapy regimens. The
      eradication rates were 78.8% (89/113 patients; 95% CI 70.1, 85.9) in group A and
      83.0% (93/112 patients; 95% CI 74.8, 89.5) in group B. Genetic polymorphism of
      CYP2C19, a major metabolic enzyme of omeprazole, did not affect eradication
      rates, while susceptibility to clarithromycin greatly affected the success of
      eradication. The cumulative ulcer relapse rate at 24 weeks after endoscopically
      documented ulcer healing (30 weeks after completion of the drug regimen) was 8.3%
      for group A and 12.5% for group B (log rank test: p = 0.6248). However,
      comparison of the cumulative relapse rate of 6.7% in patients after successful H.
      pylori eradication with the relapse rate of 27.3% in those who failed H. pylori
      eradication revealed a significant difference in the remission-time curve (log
      rank test: p = 0.0047). This finding suggested the existence of a relationship
      between H. pylori eradication failure and ulcer relapse. Both drug regimens were
      well tolerated. Endoscopically proven reflux esophagitis developed in about 10%
      of patients after eradication, but was not clinically significant. CONCLUSIONS:
      One week of triple therapy with a low-dose regimen provides adequate H. pylori
      eradication in Japanese patients. CYP genetic polymorphism is of minimal clinical
      significance with both triple-therapy regimens.

PMID- 17532670
TI  - Proton pump inhibitors in acute treatment of reflux oesophagitis : a cost
      effectiveness analysis.
AB  - BACKGROUND AND AIM: Gastro-oesophageal reflux disease is a common medical problem
      that places a significant financial burden on outpatient pharmaceutical
      expenditure. A substantial proportion of this expenditure can be attributed to
      the use of proton pump inhibitors (PPIs). The aim of this analysis was to
      evaluate the cost-effectiveness of PPIs currently licensed in Italy in the acute
      treatment of reflux oesophagitis. METHODS: A decision analysis model that
      simulated the sequential management of reflux oesophagitis over the course of 8
      weeks was constructed. Healing rates were derived from a published meta-analysis
      of PPIs for reflux oesophagitis. Costs of PPIs were based on retail prices in
      Italy, endoscopies and specialist (outpatient) visits were costed on the basis of
      public tariffs, and opportunity costs were calculated for general practitioner
      visits. The clinical effectiveness of a PPI was measured in terms of the
      proportion of patients healed at 8 weeks. An incremental cost-effectiveness
      analysis was performed, using omeprazole, the recognised 'gold standard' PPI in
      Italy, as the common comparator. The perspective of the analysis was the Italian
      National Health System (NHS). A sensitivity analysis was conducted in which the
      key parameters in the model were varied according to a Monte Carlo simulation of
      1000 patients. RESULTS: Esomeprazole 40 mg/day was a dominant treatment option
      compared with omeprazole 20 mg/day (88.8% patients healed vs 82.2%, respectively;
      total treatment cost euro164.85 vs euro169.56, respectively (year of costing,
      2002). Furthermore, on the basis of the 95% CIs generated by the Monte Carlo
      simulation, esomeprazole 40 mg/day appears to be more cost-effective than both
      lansoprazole 30 mg/day and pantoprazole 40 mg/day. CONCLUSIONS: Esomeprazole 40
      mg/day can be considered a cost-effective treatment option for the acute
      treatment of reflux oesophagitis in Italy.

PMID- 17532669
TI  - Immunogenicity and Reactogenicity following Primary Immunisation with a Combined
      DTaP-HBV Vaccine and a Haemophilus influenzae Type B Vaccine Administered by
      Separate or Mixed Injection.
AB  - OBJECTIVES: The aim of this open, randomised, multicentre trial was to evaluate
      the immunogenicity and reactogenicity of the tetravalent diphtheria-tetanus
      acellular pertussis-hepatitis B (DTaP-HBV) vaccine when given either as a mixed
      or as a separate concomitant injection with the Haemophilus influenzae type b
      (Hib) vaccine at 3, 5 and 11 months of age. METHODS: Antibody against diphtheria,
      tetanus, pertussis (ELISA), hepatitis B (radioimmunoassay) and Hib
      polyribosylribitol phosphate (PRP) [radiolabeled antigen binding assay] was
      determined. Solicited local and systemic adverse events were evaluated on the day
      of each vaccination and for three subsequent days. Follow-up of unsolicited and
      serious adverse events was conducted for 30 days following each vaccination.
      RESULTS: A total of 360 subjects were enrolled in the study. After completion of
      the three-dose vaccination course, seroprotective antibody concentrations against
      diphtheria, tetanus and hepatitis B, together with a pertussis vaccine response,
      were seen in almost all subjects with immunogenicity results (n = 336). All
      subjects had post-vaccination Hib anti-PRP antibody concentrations of at least
      0.15 mug/mL, and 97.0% and 99.4%, respectively, of the subjects receiving a
      single or separate injections had Hib anti-PRP antibody concentrations >/=1.0
      mug/mL. Addition of the Hib vaccine to the tetravalent DTaP-HBV vaccine did not
      increase the incidence of local or systemic reactions. CONCLUSIONS: Combination
      of DTaP-HBV and Hib vaccines in a single injection is safe, immunogenic and well
      tolerated, and thus has the potential to simplify the childhood immunisation
      schedule in Italy.

PMID- 17532671
TI  - Pioglitazone lowers blood pressure in hypertensive patients with type 2 diabetes
      mellitus : an open, multicentre, observational study.

PMID- 17532672
TI  - Pioglitazone Improves Diabetic Dyslipidaemia in Patients with Type 2 Diabetes
      Mellitus with or without Lipid-Lowering Therapy.

PMID- 17532673
TI  - Effects of pioglitazone and insulin on tight glycaemic control assessed by the
      continuous glucose monitoring system : a monocentric, parallel-cohort study.

PMID- 17532674
TI  - Transforaminal Epidural Injection Induces Hypertensive Crisis in a Patient whose
      Nifedipine was Withdrawn.

PMID- 17532675
TI  - Panic Attack Precipitated by Tegaserod plus Fluoxetine.

PMID- 17532676
TI  - Effect of once-daily alfuzosin on urinary symptoms and flow rate in benign
      prostatic hyperplasia : a 24-hour home-uroflowmetry evaluation.
AB  - OBJECTIVE: To analyse the clinical and 24-hour urinary flow efficacy of alfuzosin
      10mg once daily (OD), by means of the International Prostate Symptom Score (I
      PSS) and home-based uroflowmetry (P-Flow) measurement, in patients with lower
      urinary tract symptoms (LUTS) related to benign prostatic hyperplasia. MATERIALS
      AND METHODS: In this open-label trial, 12 male patients (median age 67 years)
      with an I-PSS >15 (median 16) and maximum urinary flow (Q(max)) <15 mL/sec were
      evaluated. Patients underwent two days of P-Flow evaluation, and then received
      alfuzosin 10mg OD from day 3 to day 9. On days 7 and 8 they underwent further P
      Flow evaluation. A second post-baseline evaluation I-PSS was recorded on day 9.
      RESULTS: Overall, 328 urinary flows were recorded and evaluated, an average of 27
      flows per patient. A statistically significant improvement in mean maximum flow:
      (Q(max)) [10.8 +/- 2.8 vs 12.4 +/- 3 mL/sec; p = 0.02] and urinary voiding volume
      (219 +/- 70 vs 233 +/- 55mL; p = 0.04) were observed after treatment compared
      with baseline. No differences in the number of urinary flows were observed
      between baseline and after treatment (13 +/- 2.9 vs 14 +/- 1.8 flows; p = 0.199).
      A statistically significant difference between the two evaluations was noted for
      I-PSS (15.7 +/- 0.8 and 9.5 +/- 2; p = 0.02). Mean Q(max) recorded during
      treatment was always higher than baseline at different daytime evaluations.
      CONCLUSION: The alfuzosin 10mg OD formulation showed a significant improvement in
      I-PSS as well as a significant improvement in urinary flow parameters (Q(max)and
      urinary voiding volume) lasting for 24 hours in patients with LUTS.

PMID- 17532677
TI  - Effect of imidapril and nifedipine on left ventricular hypertrophy in untreated
      hypertension.
AB  - OBJECTIVE: Imidapril is an ACE inhibitor that is licensed for use in the
      treatment of hypertension. Studies assessing regression of left ventricular
      hypertrophy are limited, especially those comparing imidapril with other
      antihypertensive agents. DESIGN AND SETTING: Single-centre, randomised, double
      blind, double-dummy, parallel-group study carried out in a district general
      hospital. METHODS: Eighty-six patients with untreated hypertension and left
      ventricular hypertrophy were included in the study. The mean age of the study
      population was 54 years and 70% were male. Patients were randomised to treatment
      with either imidapril or sustained-release nifedipine over a 24-week period. MAIN
      OUTCOME MEASURE AND RESULTS: Efficacy was assessed using clinic cuff blood
      pressure (BP) measurement, ambulatory BP measurement and serial transthoracic
      echocardiography. In the nifedipine and imidapril groups, respectively, there
      were significant reductions in clinic BP (16.8mm Hg [20.1, 13.4] vs 11.8mm Hg
      [15.3, 8.4] drop in mean [95% CI] arterial pressure), ambulatory BP (9.0mm Hg
      [13.2, 4.9] vs 9.7mm Hg [13.8, 5.7]) and left ventricular mass index (26.4 g/m(2)
      [36.3, 16.5] vs 20.8 g/m(2)[27.4, 4.1]). No significant differences in effects on
      these parameters were noted between the nifedipine and imidapril treatment groups
      (p = ns). There were no significant changes in left ventricular end-diastolic
      volume, left ventricular end-systolic volume, or stroke volume. Patients on
      imidapril were more likely to complete the study and experienced fewer adverse
      effects. CONCLUSIONS: Imidapril is a well tolerated ACE inhibitor that has been
      shown to be as efficacious as sustained-release nifedipine in the treatment of
      hypertension and left ventricular hypertrophy in patients with previously
      untreated hypertension.

PMID- 17532678
TI  - Efficacy and Tolerability of a Fixed Combination of Cinnarizine and
      Dimenhydrinate versus Betahistine in the Treatment of Otogenic Vertigo : A Double
      Blind, Randomised Clinical Study.
AB  - INTRODUCTION: Peripheral vestibular disorders frequently lead to the
      manifestation of symptoms of vertigo. The objective of this study was to compare
      the efficacy and tolerability of a fixed combination of cinnarizine 20mg and
      dimenhydrinate 40mg per tablet with betahistine (betahistine dimesylate) 12mg per
      tablet in the treatment of patients with otogenic vertigo. PATIENTS AND METHODS:
      Sixty-one patients with vertigo due to peripheral vestibular disorders (otogenic
      vertigo) participated in this prospective, double-blind, comparative, single
      centre study. Patients were randomly allocated to treatment with betahistine 12mg
      or the fixed combination of cinnarizine 20mg and dimenhydrinate 40mg, both
      treatments given three times daily for 4 weeks. Efficacy was determined by
      patients' assessments of vertigo symptoms after 1 and 4 weeks of treatment using
      a visual analogue scale to determine a 'mean vertigo score'. RESULTS: Treatment
      with the fixed combination led to significantly greater improvements in mean
      vertigo scores compared with the reference therapy betahistine. This was evident
      as early as 1 week after the onset of treatment (p = 0.002). Over 4 weeks of
      therapy, the fixed combination decreased the intensity of vertigo symptoms about
      2-fold compared with betahistine (p = 0.001). Furthermore, reductions in symptoms
      typically associated with vertigo were more pronounced (p = 0.009) in the fixed
      combination group compared with the betahistine group after 4 weeks of treatment.
      No serious adverse events were reported in either treatment group. Tolerability
      of the fixed combination was judged as 'very good' by 97% (betahistine 90%) and
      as 'good' by 3% (betahistine 10%) of patients. CONCLUSION: The fixed combination
      of cinnarizine and dimenhydrinate was shown to be an effective and very well
      tolerated treatment option for patients with otogenic vertigo. It proved to be
      statistically more efficient in reducing vertigo than the widely used
      betahistine. Therefore, the fixed combination of cinnarizine and dimenhydrinate
      may be considered a first-line treatment option for the treatment of otogenic
      vertigo.

PMID- 17532679
TI  - Bioavailability and bioequivalence of two enteric-coated formulations of
      omeprazole in fasting and fed conditions.
AB  - OBJECTIVE: To investigate the relative bioavailability and bioequivalence, in
      fasting and fed conditions, of repeated doses of two omeprazole enteric-coated
      formulations in healthy volunteers. MATERIAL AND METHODS: Open label, single
      centre study consisting of two consecutive randomised, two-way crossover trials
      (a fasting trial and a fed trial). Each trial consisted of two 7-day treatment
      periods in which subjects received one daily dose of the test (Ompranyt((R))) or
      reference (Mopral((R))) formulations. At day 7 and day 14 (fasting trial),
      products were administered in fasting conditions and blood samples were taken for
      omeprazole plasma assay over 12 hours. At day 21 and day 28 (fed trial), products
      were administered after a standard high-calorie and high-fat meal and 12-hour
      blood samples taken. Omeprazole plasma concentrations were quantified by a
      validated method using a reverse-phase high performance liquid chromatography
      with UV detection (HPLC-UV). RESULTS: Twenty-four subjects were enrolled and 23
      completed the study. Under fasting conditions, the mean +/- SD maximum omeprazole
      plasma concentration (C(max)) was 797 +/- 471 mug/L for Ompranyt((R)) and 747 +/-
      313 mug/L for Mopral((R)) with a point estimate (PE) of 1.01 and a 90% confidence
      interval (CI) of 0.88, 1.16. The mean +/- SD area under the plasma concentration
      curve from administration to last observed concentration (AUC(0-12)) was 1932 +/-
      1611 mug . h/L and 1765 +/- 1327 mug . h/L for Ompranyt((R)) and Mopral((R)),
      respectively (PE = 1.09; 90% CI 0.95, 1.25). In the presence of food, the C(max)
      was 331 +/- 227 mug/L and 275 +/- 162 mug/L (PE = 1.21; 90% CI 0.92, 1.59) and
      AUC(0-12) was 1250 +/- 966 mug . h/L and 1087 +/- 861 mug . h/L (PE = 1.16; 90%
      CI 0.92, 1.47) for Ompranyt((R)) and Mopral((R)), respectively. Bioequivalence of
      the formulations in the fasting condition was demonstrated both for AUC(0-12) and
      for C(max) because the 90% CI lay within the acceptance range of 0.80-1.25. In
      contrast with the fasting condition, there were significant reductions in rate
      (C(max)) and extent (AUC(0-12)) of systemic exposure when test and reference
      formulations were administered with food. The food effect was more marked with
      Mopral((R)) than with Ompranyt((R)), and the bioequivalence criterion was not
      fulfilled because the 90% CI fell out of the acceptance range of 0.80, 1.25, for
      both C(max) and AUC(0-12). The two formulations were similarly well tolerated.
      CONCLUSION: Bioequivalence of Ompranyt((R)) (test formulation) and Mopral((R))
      (reference) formulations was demonstrated after repeated dosing in the fasting
      condition. Following a high-calorie and high-fat meal, there was a significant
      reduction in rate and extent of systemic exposure for both products, with
      Ompranyt((R)) being less affected than Mopral((R)) by the presence of food.

PMID- 17532680
TI  - High-dose N-acetylcysteine in patients with exacerbations of chronic obstructive
      pulmonary disease.
AB  - OBJECTIVE: To investigate the efficacy and tolerability of high-dose N
      acetylcysteine (NAC) in the treatment of patients with exacerbations of chronic
      obstructive pulmonary disease (COPD). DESIGN AND PATIENTS: Randomised, double
      blind, double-dummy, placebo-controlled study in 123 patients experiencing an
      acute exacerbation of COPD. INTERVENTIONS: NAC 1200 mg/day, 600 mg/day or placebo
      administered once daily for 10 days. MAIN OUTCOME MEASURES: The primary objective
      was to assess the proportion of patients with normalised C-reactive protein (CRP)
      levels. Also assessed were effects on interleukin (IL)-8 levels, lung function
      and symptoms. RESULTS: Both NAC 600 and 1200 mg/day were associated with a
      significantly higher proportion of patients achieving normalised CRP levels
      compared with placebo (52% and 90% vs 19% of patients; p </= 0.01); however, NAC
      1200 mg/day was superior to NAC 600 mg/day (p = 0.002). Furthermore, treatment
      with NAC 1200 mg/day was more efficacious than NAC 600 mg/day in reducing IL-8
      levels and difficulty of expectoration, while the two active regimens had similar
      beneficial effects on lung function and other clinical outcomes (cough intensity
      and frequency, and lung auscultation). Treatments were well tolerated with one
      adverse event reported in NAC 1200 mg/day recipients and two reported in placebo
      recipients. CONCLUSION: Treatment with NAC 1200 mg/day improved biological
      markers and clinical outcomes in patients with COPD exacerbations. It is
      speculated that the effect of NAC on inflammatory markers may be due to both
      mucolytic and antioxidant properties.

PMID- 17532681
TI  - A Randomised Comparison of the Effects of Nebivolol and Atenolol with and without
      Chlorthalidone on the Sexual Function of Hypertensive Men.
AB  - BACKGROUND AND OBJECTIVE: Erectile dysfunction, which is common in men with
      hypertension, has been reported as a common adverse effect of many
      antihypertensive drug classes, including beta-blockers and diuretics. Atenolol
      and nebivolol are both beta(1)-selective blockers, but nebivolol is a new
      generation compound with nitric oxide-mediated vasodilating activity. The aim of
      the study was to compare the effects of nebivolol and atenolol +/- chlorthalidone
      on the sexual function of hypertensive men. METHODS: A total of 131 male patients
      (mean age 47.3 +/- 4.6 years) with newly diagnosed hypertension were included in
      the study. All the patients were married and had not previously experienced any
      erectile dysfunction. After a 4-week placebo run-in period, patients were
      randomised to receive 12 weeks' therapy with nebivolol 5 mg/day (n = 43),
      atenolol 50 mg/day (n = 44), or atenolol 50 mg/day + chlorthalidone 12.5 mg/day
      (n = 44), according to a double-blind design. After 4 weeks of treatment, drug
      dosage could be doubled in patients not responding to therapy. Erectile function
      (instances of successful intercourse/month) was assessed by means of a
      questionnaire at the end of the placebo run-in period (baseline) and at the end
      of double-blind treatment. Blood pressure was also assessed at these times.
      RESULTS: At the end of the 12-week, double-blind treatment period, the mean
      number of episodes of satisfactory sexual intercourse per month was significantly
      decreased from baseline in the groups receiving atenolol (from 7.0 to 3.7; p <
      0.01) and atenolol + chlorthalidone (from 6.4 to 2.8; p < 0.01). In contrast, the
      mean number of episodes of satisfactory sexual intercourse per month remained
      constant in the group of patients receiving nebivolol (6.4 during the baseline
      assessment and 6.0 during the last month of treatment). Blood pressure and heart
      rate were significantly decreased from baseline in all treatment groups.
      CONCLUSION: Increased release of nitric oxide associated with nebivolol may
      counteract the detrimental effect of beta-blockade on penile erection, thereby
      allowing maintenance of sexual activity in previously untreated hypertensive men
      compared with a significant decrease observed in the sexual activity of men
      receiving atenolol-based treatment.

PMID- 17532682
TI  - Successful Treatment with Colesevelam HCl and Pravastatin in a Patient Previously
      Hospitalised with Severe Normal CPK Myopathy on Introduction of Simvastatin.

PMID- 17532683
TI  - Nimesulide-induced hepatotoxicity in a previously healthy woman.

PMID- 17532684
TI  - No influence of food on the pharmacokinetics, pharmacodynamics or tolerability of
      the 24mg and 36mg oral tablet formulations of ximelagatran.
AB  - OBJECTIVE: To assess the potential effects of food on the pharmacokinetics and
      tolerability/safety of ximelagatran, an oral direct thrombin inhibitor developed
      for the prevention and treatment of thromboembolic disease that is rapidly
      bioconverted to its active form, melagatran. DESIGN AND STUDY PARTICIPANTS: In
      two open-label, randomised, crossover studies, healthy male and female volunteers
      received oral ximelagatran as a single 24mg tablet (study 1, n = 30) or a single
      36mg tablet (study 2, n = 50). Potential effects of food on the pharmacodynamics
      (activated partial thromboplastin time; APTT) of the 36mg tablet were also
      investigated in study 2. RESULTS: For the 24mg tablet, the 90% confidence
      intervals (CIs) and least-squares mean estimates for the ratio of the tablet with
      food to the tablet without food fell within the predefined bounds demonstrating
      no effect on area under the melagatran concentration-time curve (AUC ratio = 0.94
      [90% CI 0.90, 0.99]) or maximum plasma concentration (C(max) ratio = 0.88 [90% CI
      0.82, 0.95]). The same result was observed for the 36mg tablet (AUC ratio = 1.07
      [90% CI 1.03, 1.12]; C(max) ratio = 1.05 [90% CI 0.98, 1.12]). Melagatran AUC
      normalised for differences in bodyweight was comparable between women and men
      administered the 24mg or 36mg tablet without food. In addition, food did not
      clinically significantly alter the melagatran-induced prolongation of the APTT of
      the 36mg tablet. Ximelagatran was well tolerated with or without food.
      CONCLUSION: The pharmacokinetics (AUC, C(max)), pharmacodynamics (APTT) and
      tolerability of melagatran after administration of oral ximelagatran tablets were
      not affected by food.

PMID- 17532685
TI  - Tramadol SR Formulations : Pharmacokinetic Comparison of a Multiple-Units Dose
      (Capsule) versus a Single-Unit Dose (Tablet).
AB  - INTRODUCTION: Different oral sustained-release (SR) formulations of tramadol have
      been introduced in pain treatment in order to prolong the dosage interval to
      improve convenience for the patient. The objective of this study was to compare
      tramadol pharmacokinetics and intra- and intersubject variability after replicate
      single-dose administrations of a multiple-units SR formulation (capsule) and a
      single-unit formulation (tablet). METHODS: This was a randomised, single-dose,
      single-centre study with an open-label, four-period, two-sequence, two
      formulation, replicate crossover design in healthy subjects under fed conditions.
      The main outcome measures were the intra- and intersubject variance of the area
      under the concentration-time curve from 0 to 12 hours (AUC(12)) and maximum
      concentration (C(max)), as well as the mean AUC(12) and C(max) for tramadol.
      Study drugs were a tramadol SR multiple-units formulation (capsule) and a
      tramadol SR single-unit formulation (tablet), each containing tramadol
      hydrochloride 100mg. The time interval from 0 to 12 hours of AUC(12) of the
      single-dose design corresponds to the recommended twice-daily dosage interval for
      both study drugs during long-term treatment. RESULTS: The two formulations were
      equivalent in the area under the curve (AUC(infinity): 2411 vs 2527 mug . h/L).
      However, capsules led to a lower C(max) (148.6 vs 183.2 mug/L), to a later time
      to reach C(max) (5.9 vs 4.9 hours), and to a longer half-value duration (13.4 vs
      10.4 hours). In addition, intrasubject variability of AUC(12) was significantly
      smaller for capsules than for tablets (p = 0.041). Capsules also produced smaller
      intra- and intersubject variability in plasma concentrations during the first 2.5
      and 3.0 hours after administration, respectively (p < 0.05). CONCLUSION: Although
      tramadol SR capsules and tramadol SR tablets led to an equivalent systemic
      exposure to the drug, capsules provided a smoother and more extended plasma
      profile. In addition, in the case of capsules, bioavailability was subjected to
      lower variability in terms of both rate and extent of absorption.

PMID- 17532686
TI  - Efficacy of a fixed-dose combination of trandolapril-verapamil in patients with
      stage 2 hypertension inadequately controlled by monotherapy.
AB  - BACKGROUND AND OBJECTIVE: About 70% of hypertensive patients need more than one
      drug to control their blood pressure (BP). The Seventh Report of the Joint
      National Committee on Prevention, Detection, Evaluation, and Treatment of High
      Blood Pressure recommends a two-drug combination as initial drug therapy for
      patients with stage 2 hypertension. The aim of this study was to determine if a
      fixed-dose combination of trandolapril-verapamil is effective and safe in the
      treatment of stage 2 (moderate to severe) hypertension in hypertensive Mexican
      patients not controlled by monotherapy. METHODS: Forty hypertensive patients with
      BP >160/100mm Hg despite >6 months of drug treatment were given the fixed-dose
      combination of trandolapril-verapamil (2mg/180mg) for 12 weeks. Before taking the
      drug, they measured their own blood pressure (self-measured BP [SMBP]) several
      times a day for 3 days using a validated Omrom HEM 713C BP measuring device. At
      the end of the 12-week treatment period, the patients performed a second series
      of SMBPs in the same way as before treatment. A washout period was not included
      because the patients did not have an adequate response to previous
      antihypertensive treatment. Antihypertensive control during the 3-day SMBP period
      was evaluated. RESULTS: Patients experienced a significant reduction in mean BP
      (from 180/100mm Hg to 135/78mm Hg; p < 0.001). Seventy-five percent of patients
      reached their therapeutic goals (BP <140/90mm Hg). The SMBP records showed that
      BP values were maintained throughout the entire 3 days. One patient experienced
      headache and one had constipation; no patients discontinued the treatment.
      CONCLUSION: A fixed-dose combination of trandolapril-verapamil seems to be an
      effective and safe option for the management of stage 2 hypertension in Mexican
      patients uncontrolled by monotherapy.

PMID- 17532687
TI  - Effects of Different Combined Bronchodilator Therapies on Airway Inflammation in
      COPD.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterised by
      chronic progressive airway obstruction and inflammation. Only a few studies have
      evaluated the effects of bronchodilator therapy on airway inflammation in
      patients with COPD. OBJECTIVE: The aim of this study was to investigate the
      effects of different combinations of bronchodilator therapies on airway
      inflammation in COPD. METHODS: Thirty patients with COPD and ten healthy
      nonsmoker subjects were included in the study. COPD patients were randomly
      classified into three groups. Groups 1, 2 and 3 were treated with ipratropium
      bromide plus formoterol (IP + FOR), theophylline plus ipratropium bromide (IP +
      THEO), and formoterol plus theophylline (FOR + THEO), respectively, for 12 weeks.
      Pulmonary function tests were performed, blood was drawn for arterial blood gas
      analyses, and sputum was induced before and after treatment. The induced sputum
      total and differential cell counts, serum and sputum inflammatory markers
      including interleukin (IL)-8, tumour necrosis factor (TNF)-alpha and leukotriene
      (LT)-B4 were measured. RESULTS: When compared with the control group, total
      sputum cell counts, number of neutrophils, and sputum and serum inflammatory
      marker levels were significantly higher in COPD patients. Although there were no
      statistically significant differences among the groups, inflammatory parameters
      were found to be significantly reduced in all three treatment groups at the end
      of treatment. Total cell counts were: 2.4 +/- 0.9 versus 1.28 +/- 0.5 x
      10(6)cells/g in the IP + FOR group (p < 0.05), 2.32 +/- 0.4 versus 1.37 +/- 0.6 x
      10(6)cells/g in the IP + THEO group (p < 0.05), and 3.05 +/- 1.3 versus 1.6 +/-
      0.8 x 10(6)cells/g in the FOR + THEO group (p < 0.05). Sputum IL-8 levels were:
      1738.5 +/- 292 versus 848 +/- 262 ng/L in the IP + FOR group (p < 0.05), 1543.2
      +/- 378 versus 800.2 +/- 224 ng/L in the IP + THEO group (p < 0.05), and 1561.2
      +/- 412 versus 815.7 +/- 259 ng/L in the FOR + THEO group (p < 0.05). CONCLUSION:
      Different combinations of bronchodilator therapies caused significant changes in
      sputum and blood IL-8, TNF-alpha and LTB4 levels of COPD patients without
      significantly improving pulmonary function tests or arterial blood gas
      parameters.

PMID- 17532688
TI  - Utilisation and safety of bemiparin, a low-molecular-weight heparin, in medical
      patients : a prospective, uncontrolled cohort study.
AB  - INTRODUCTION: Venous thromboembolism (VTE) is the cause of approximately 10-12%
      of all deaths occurring in hospitalised patients. In a previous study, bemiparin
      suppressed markers of hypercoagulability in acutely ill medical patients with
      heart failure. OBJECTIVE: To estimate the rate of symptomatic VTE, bleeding
      events, thrombocytopenia and death in acutely ill medical patients treated with
      low and high prophylactic doses of bemiparin in standard clinical practice.
      METHODS AND PATIENTS: This was a prospective, open, multicentre, non-randomised
      cohort study. Acutely ill patients hospitalised in medical departments were
      included and treated with bemiparin 2500 IU/day or 3500 IU/day, depending on the
      degree of VTE risk (moderate or high) as assessed by the investigator. The main
      efficacy and safety endpoints were: symptomatic confirmed VTE (deep vein
      thrombosis and pulmonary embolism), major bleeding, thrombocytopenia and death.
      The observation period was 41 days. A total of 297 medical patients hospitalised
      for several reasons (lung disease: 87 [29.3%], heart disease: 80 [26.9%],
      neurological disease 25 [8.4%], gastrointestinal disease: 18 [6.1%], rheumatic
      disorder: 14 [4.7%], haematological disease: 11 [3.7%], renal disease: 8 [2.7%],
      other: 54 [18.2%]) were included from 13 centres in Spain. The median age of the
      patients included was 78 years (range 31-100). Overall, 208 patients received
      bemiparin 2500 IU/day and 89 patients received bemiparin 3500 IU/day. RESULTS:
      There was one case of symptomatic VTE in 297 patients (0.3%). Four patients
      (1.3%) experienced a major bleeding event. There were two cases (0.7%) of mild
      moderate type I heparin-induced thrombocytopenia (HIT) during the treatment
      period that did not require treatment discontinuation. There were no cases of
      severe type II HIT. A total of 22 (7.4%) patients died during the treatment
      period as a result of factors unrelated to VTE. CONCLUSIONS: Bemiparin appears to
      be effective and safe in the prevention of VTE in acutely ill medical patients.

PMID- 17532690
TI  - Embolia cutis medicamentosa (nicolau syndrome) : two cases due to different drugs
      in distinct age groups.

PMID- 17532689
TI  - Efficacy and Safety of Olmesartan in the Treatment of Mild-to-Moderate Essential
      Hypertension in Chinese Patients.
AB  - BACKGROUND AND OBJECTIVE: Hypertension is very prevalent in the Chinese
      population in Taiwan. Chinese people frequently experience bothersome cough when
      receiving angiotensin-converting enzyme (ACE) inhibitors, and angiotensin II
      (AT(1)) receptor antagonists are thus relatively more frequently used in this
      context. In this trial we studied the effectiveness of a new AT(1) receptor
      antagonist, olmesartan, in the treatment of Chinese patients with mild-to
      moderate essential hypertension. PATIENTS AND METHODS: The present study was a
      double-blind, randomised, multicentre trial to compare the efficacy and safety
      profiles of two AT(1) receptor antagonists, olmesartan and losartan, in the
      treatment of Chinese patients with mild-to-moderate essential hypertension. 126
      adults were randomised to receive either once-daily olmesartan 20mg or once-daily
      losartan 50mg for 12 weeks. There were 49 evaluable patients in the olmesartan
      group and 57 in the losartan group. RESULTS: At baseline, neither diastolic (DBP)
      nor systolic (SBP) blood pressures were significantly different between the two
      study groups. Trough blood pressures were measured and recorded for the
      evaluation of treatment effect. After drug treatment for 4, 8 and 12 weeks, SBP
      and DBP values were significantly decreased in both groups of patients. However,
      both SBP and DBP were significantly lower in the olmesartan group than in the
      losartan group after treatment. At the end of treatment, DBP values were 87.0 +/-
      8.6mm Hg versus 91.6 +/- 8.7mm Hg (p < 0.001) and SBP values were 129.5 +/-
      12.6mm Hg versus 135.4 +/- 12.1mm Hg (p < 0.001) in the olmesartan and losartan
      groups, respectively. After 4 weeks of treatment, the reduction in BP values was
      larger in the olmesartan group than in the losartan group (decreases in DBP of
      12.1 +/- 8.4mm Hg vs 7.2 +/- 6.8mm Hg [p < 0.005] and in SBP of 15.1 +/- 13.0mm
      Hg vs 10.3 +/- 10.1mm Hg [p < 0.05] for the olmesartan and losartan groups,
      respectively). Patients treated with either drug experienced only mild adverse
      reactions, such as dizziness, cough, headache and neck pain, all of which
      occurred at low frequencies. There were no significant changes in laboratory
      parameters. CONCLUSION: Both olmesartan and losartan are effective and safe in
      the treatment of Chinese patients with mild-to-moderate essential hypertension.
      Olmesartan 20mg once daily is more potent and has a more rapid antihypertensive
      effect than losartan 50mg once daily in the treatment of mild-to-moderate
      hypertension in Chinese patients.

PMID- 17532691
TI  - Clarithromycin in the Treatment of Legionella pneumophila Pneumonia Associated
      with Multiorgan Failure in a Previously Healthy Patient.

PMID- 17532692
TI  - Pharmacokinetics and Safety of ABT-578, a Sirolimus (Rapamycin) Analogue, after
      Single Intravenous Bolus Injection in Healthy Male Volunteers.
AB  - OBJECTIVE: ABT-578, a tetrazole analogue of sirolimus (rapamycin), possesses anti
      restenosis activity. The aim of this study was to assess the safety and
      pharmacokinetics of escalating single intravenous (IV) doses of ABT-578 in a
      phase 1, double-blind, randomised, placebo-controlled study. METHODS: Sixty adult
      healthy males were divided into five IV-dose groups of 100, 300, 500, 700 and
      900mug. Doses were administered as IV bolus over 3 minutes, with eight subjects
      and four subjects receiving ABT-578 and placebo, respectively, in each dose
      group. Higher doses were administered after evaluating safety from the preceding
      lower doses. Blood concentrations of ABT-578 were sampled for 168 hours and
      measured using LC-MS/MS with a limit of quantification of 0.20 ng/mL. RESULTS:
      The pharmacokinetics of ABT-578 were essentially linear across the 100-900microg
      dose range as illustrated by the dose-proportional increases in concentration at
      5 minutes (C(5)) after the end of infusion and area under the concentration-time
      curve (AUC). The mean half-life ranged between 26.0 and 40.2h over the studied
      doses and was not significantly different over the 300-900mug dose range. The
      mean clearance values ranged from 2.90 to 3.55 L/h. Single IV bolus doses up to
      900mug of ABT-578 were well tolerated and no clinically significant changes in
      physical examination results, vital signs or laboratory test results were
      observed. CONCLUSION: It can be concluded that the pharmacokinetics of IV ABT-578
      are dose-proportional over the 100-900mug dose range. Single IV bolus doses up to
      900mug were well tolerated in healthy male subjects.

PMID- 17532693
TI  - Role or carbon dioxide-releasing suppositories in the treatment of chronic
      functional constipation: a double-blind, randomised, placebo-controlled trial.
AB  - OBJECTIVE: Treatment of chronic functional constipation is difficult. Both oral
      and topical laxatives may fail to adequately relieve symptoms, and there is risk
      of adverse effects such as functional or structural changes in the intestine,
      together with electrolyte disturbances. The aim of this study was to evaluate the
      efficacy and safety of a suppository that combines sodium bicarbonate and
      potassium bitartrate in a polyethylene glycol base to generate approximately
      175mL of carbon dioxide (CO(2)). This release distends the rectal ampulla,
      thereby stimulating peristalsis and a subsequent bowel movement. PATIENTS AND
      METHODS: This was a prospective, crossover, double-blind, randomised, placebo
      controlled, sequential study of outpatients with chronic functional constipation.
      Each patient received two suppositories of identical appearance, containing
      active drug or placebo. The sequence of active drug-placebo (sequence 1) or
      placebo-active drug (sequence 2) was randomised in groups of eight. The second
      suppository was taken 7 days after the first. The following parameters were
      evaluated and scored: evacuation time, type of evacuation, feeling of emptying of
      the rectal ampulla, stool characteristics, anal complaints, abdominal pain and
      overall patient assessment. RESULTS: A total of 29 patients entered the study.
      According to a restricted sequential plan, a statistical significance (p < 0.05)
      in favour of the active drug was reached after 26 patients. A positive response
      within 30 minutes of introduction of the suppository occurred in 51.7% and 6.9%
      of patients treated with the active drug and placebo, respectively (p = 0.0003).
      Normal evacuation occurred in 65.5% and 24.1% of patients treated with the active
      drug and placebo, respectively (p = 0.004). Normal stool consistency was found in
      44.8% and 7.2% of patients treated with the active drug and placebo, respectively
      (p = 0.04). Patient assessment of treatment as satisfactory occurred in 51.7% and
      20.7% of subjects treated with the active drug and placebo, respectively (p =
      0.029). Only a trend in favour of the active drug was observed with regard to
      feeling of incomplete evacuation, and active drug was comparable to placebo with
      regard to anal and abdominal tolerability CONCLUSION: The CO(2)-releasing
      suppository may represent an alternative to rectal laxatives for the relief of
      chronic functional constipation. The data obtained in this study indicate that
      CO(2)-releasing suppositories may be usefully and safely employed in the
      treatment of patients at risk for electrolyte disorders such as the elderly or
      patients with renal or cardiovascular disorders.

PMID- 17532694
TI  - Long-term effects of rivastigmine treatment on the need for psychotropic
      medications in nursing home patients with Alzheimer's disease : results of a 52
      week open-label study.
AB  - BACKGROUND AND OBJECTIVE: Neuropsychiatric symptoms and behavioural disturbances
      occur in most patients with Alzheimer's disease (AD), are a source of stress for
      caregivers, and are the primary cause of patient institutionalisation. These
      symptoms often are treated with psychotropic medications. However, adverse drug
      interactions, adverse effects and nursing home regulations make reducing the use
      of psychotropic medications in elderly AD patients an important goal of therapy.
      Fifty-two-week data including data from a 26-week prospective open-label,
      multicentre study and its 26-week open-label extension were analysed. PATIENTS
      AND METHODS: 173 patients with moderate to severe AD residing in nursing homes
      were treated with rivastigmine 1.5-6mg twice daily. In the study, psychotropic
      drug use and behavioural symptoms were measured at baseline and at 52 weeks.
      RESULTS: Results showed that 40% of patients who were receiving psychotropic
      medications at baseline had discontinued use or reduced their dose of
      psychotropic medications at week 52. Furthermore, significant improvements were
      observed from baseline in 10 of the 12 behavioural domains of the Nursing Home
      version of the Neuropsychiatric Inventory, including delusions (mean change from
      baseline -2.0; p = 0.002), hallucinations (mean change -3.1; p < 0.001), anxiety
      (mean change -1.1; p = 0.014), and euphoria (mean change -3.2; p = 0.006).
      CONCLUSION: These data suggest favourable tolerability, behavioural and
      pharmacoeconomic outcomes in nursing home residents with AD who are treated with
      rivastigmine.

PMID- 17532695
TI  - Intravenous Esomeprazole 40mg is Effective for the Control of Intragastric Acid
      Levels Whether Given as a 3-Minute Injection or a 30-Minute Infusion.
AB  - BACKGROUND: An intravenous (IV) formulation of esomeprazole has been developed as
      an alternative to oral administration. To meet the needs of different clinical
      situations it would be preferable if an IV dose could be administered as either
      an injection or an infusion, while producing similar effects. AIM: To compare the
      effects of IV esomeprazole 40mg given as a 3-minute injection or a 30-minute
      infusion on intragastric pH during single and repeated once-daily dosing in
      healthy subjects. METHODS: In this single-centre, double-blind, double-dummy,
      randomised, two- way crossover study, subjects were randomised to receive either
      a 3-minute IV injection or a 30-minute IV infusion of esomeprazole 40mg. Both
      regimens were given once daily for 10 days. After a washout period of at least 13
      days, subjects were crossed over to the other treatment. Intragastric pH
      monitoring was performed on days 1 and 10. Blood samples were also taken
      throughout days 1 and 10. RESULTS: Data were available from 41 subjects. Time
      with intragastric pH >4 was 3.1h/24h at baseline, increasing to almost 8h in
      association with IV esomeprazole injection or infusion on day 1, and to >13h on
      day 10. Geometric mean time with pH >4/24h ratios (injection/infusion) were 0.99
      on day 1 and 1.03 on day 10. Mean esomeprazole AUC values were approximately 15%
      higher with the injection than the infusion, but 90% CI limits for geometric mean
      AUC ratios ranged from 1.07 to 1.23, indicating bioequivalence. CONCLUSIONS: IV
      esomeprazole 40mg provides similarly potent acid control whether administered by
      injection or infusion.

PMID- 17532696
TI  - Antiretroviral Therapy in the Real World : Population-Based Pharmacoeconomic
      Analysis of Administration of Anti-HIV Regimens to 990 Patients.
AB  - OBJECTIVE AND METHODS: The aim of our study was to analyse retrospectively the
      nature and frequency of antiretroviral prescriptions for 990 HIV-infected
      patients followed at our outpatient centre in Bologna, Italy, from January 2003
      to March 2004. The main focus of the study was to identify the most commonly
      prescribed combinations and their related expenses, in order to identify the most
      competitive treatment regimens with regard to costs. Prescriptions were given
      directly to patients at monthly intervals, and drug treatment adherence data was
      stored in an electronic database. Antiretroviral regimens administered for the
      longest period to each patient during the 15 months of the study were selected
      for the study. All patients treated for <9 consecutive months and/or with
      treatment adherence levels <90% were excluded. Physicians assessed antiretroviral
      therapy at least quarterly according to efficacy and safety criteria, but not in
      terms of pharmacoeconomic considerations. Direct pharmacy expenses were obtained
      for the 24 most commonly used therapeutic regimens, covering 80.1% of patients.
      RESULTS: The zidovudine-lamivudine-efavirenz combination proved to be the most
      prescribed combination (7.3%), followed by zidovudine-lamivudine- nevirapine
      (7.1%), lamivudine-stavudine (6.2%), zidovudine-lamivudine- lopinavir-ritonavir
      (5.2%), didanosine-stavudine-lopinavir-ritonavir (4.8%), and lamivudine-stavudine
      nevirapine (4.7%). Anti-HIV combinations varied from a minimum yearly cost of
      euro3895.6 for lamivudine-stavudine to euro9422.8 for the zidovudine-lamivudine
      lopinavir-ritonavir combination (+241.9%) [year of costing 2003]. There was a
      significant difference between the two first-line regimens for antiretroviral
      naive subjects, with lopinavir-ritonavir-based combinations costing more than
      euro9000 per patient/year compared with efavirenz-containing combinations, which
      were 28% less expensive. Mean daily costs varied substantially, from a minimum of
      euro10.7 per day for lamivudine-stavudine to a maximum of euro25.8 per day
      (+241.1%) for zidovudine-lamivudine-lopinavir-ritonavir. Regimens based on non
      nucleoside reverse transcriptase inhibitors (NNRTIs) were less costly than most
      of those including protease inhibitors (PIs). The increased expense of each
      combination was compared with the cheapest therapeutic selection (lamivudine
      stavudine), and costs of all triple combinations were also compared. Regimens
      based on NNRTIs accounted for 29.3% of our cohort (nevirapine-containing
      therapies 15.1%, and efavirenz-based ones 14.2%), while PIs were used in the
      majority of cases (37.3%), with lopinavir-ritonavir as the leading combination
      (13.6% of patients), followed by nelfinavir (9.9%) and indinavir (9.2%). When
      drug-related costs were examined, dual nucleoside analogues showed the lowest
      expense (euro10.7-euro11.6 per day), while triple nucleoside/nucleotide analogue
      combinations cost nearly twice as much (euro18.5-euro20.4 per day). Among the
      NNRTIs, there were comparable costs for nevirapine-based combinations (euro18.3
      euro18.7 per day), while efavirenz-including regimens were 10% more costly
      (euro19.2-euro20.l per day). A very broad range of combinations and related costs
      were found with PIs, but apart from indinavir and saquinavir combinations
      (euro15.7-euro21.7 per day), all other regimens had a higher daily cost (from
      euro22.0 per day for ritonavir-based regimens to euro23.4-euro24.3 per day for
      nelfinavir combinations, and up to euro24.9-euro25.8 per day with lopinavir
      ritonavir). When considering nelfinavir- and lopinavir-containing combinations,
      the difference compared with NNRTI-based regimens varied from 41% when nevirapine
      and lopinavir-ritonavir were compared, to 11.6% when efavirenz and nelfinavir
      were compared. CONCLUSIONS: Investigations that link prescribing patterns and
      related costs in the setting of HIV disease therapy are needed to improve patient
      management and help with the planning of healthcare resource allocation.

PMID- 17532697
TI  - Efficacy of Lignocaine plus Ketamine at Different Doses in the Prevention of Pain
      Due to Propofol Injection.
AB  - OBJECTIVE: Pain on injection is still a major problem with propofol. Lignocaine
      (lidocaine) is effective in preventing propofol-induced pain on injection, but
      cannot entirely control the pain. The purpose of this study was to examine the
      effect of lignocaine plus ketamine, an N-methyl-D-aspartate receptor antagonist,
      on pain on injection of propofol. DESIGN: Prospective, randomised, double-blind,
      placebo-controlled study. SETTING: University Hospital. PATIENTS: 120 female
      patients scheduled for gynaecological laparoscopy. INTERVENTIONS: Patients
      received intravenously lignocaine 20mg plus either placebo (saline) or ketamine
      at three different doses (2.5mg, 5mg and 10mg), with manual venous occlusion for
      1 minute, followed by administration of propofol 0.5 mg/kg into a dorsal hand
      vein (n = 30 in each group). A blinded researcher asked the patients to assess
      pain during the propofol injection. MAIN OUTCOMES MEASURES AND RESULTS: Twelve of
      30 patients (40%) complained of pain in the lignocaine/placebo group compared
      with three (10%) in the lignocaine/ketamine 5mg group and three (10%) in the
      lignocaine/ketamine 10mg group (both p = 0.015). No significant differences were
      found between the lignocaine/ketamine 2.5mg (10 patients [33%]) and
      lignocaine/placebo groups. No complications such as pain, oedema, wheal or flare
      response were observed at injection sites within the first 24 hours after
      anaesthesia. CONCLUSION: Combined lignocaine 20mg and ketamine 5mg, with manual
      venous occlusion, is more effective than lignocaine 20mg alone for pain control
      during propofol injection.

PMID- 17532698
TI  - Reduced Peak Inspiratory Effort through the Diskus((R)) and the Turbuhaler((R))
      due to Mishandling is Common in Clinical Practice.
AB  - OBJECTIVES: A minimum peak inspiratory flow (PIF) through dry powder inhalers
      (DPIs) is required for effective drug delivery to the lungs. Some patients are
      unable to generate the minimally effective PIF through the DPI. However, little
      information is available about the 'real life' prevalence of reduced peak
      inspiratory effort through the Diskus((R)) and the Turbuhaler((R)) as a result of
      mishandling METHODS: We investigated peak inhalation effort through the
      Diskus((R)) and the Turbuhaler((R)) by both direct observation and the In-Check
      Dial((R)), a portable PIF meter, in a large sample of patients consecutively
      referred to our laboratory who were familiar with these devices. Patients with
      reduced peak inspiratory effort repeated the PIF measurement after a session of
      instruction on the need for more forceful effort through the device. RESULTS: We
      studied 644 patients (mean age 62 years, 42% female). Of these, 62% had chronic
      obstructive pulmonary disease and 35% had asthma. The mean baseline forced
      expiratory volume in 1 second was 53% of predicted. 502 patients were using the
      Diskus((R)) and 185 the Turbuhaler((R)). Overall, 106 patients (16.5%) showed
      weak inhalation by direct observation at baseline. Of 44 subjects with weak
      inhalation through the Turbuhaler((R)), 34 (77%) demonstrated a PIF <30 L/min.
      Post-counselling, only four patients did not achieve a PIF of at least 30 L/min
      (p < 0.01). Of 62 subjects with weak inhalation through the Diskus((R)), 37 (60%)
      had a PIF <30 L/min. Post-counselling, all these subjects achieved a PIF of at
      least 30 L/min (p < 0.001). CONCLUSION: A significant number of patients show a
      reduced peak inspiratory effort through the Diskus((R)) and the Turbuhaler((R))
      in real life. Our results indicate that the cause of this deficiency is often
      mishandling of the device because, after a brief session of instruction on the
      need for more forceful inhalation, most patients obtained an acceptable PIF rate.
      A PIF meter may identify patients with inadequately weak inhalation and offer
      useful feedback for obtaining the best inspiratory effort.

PMID- 17532699
TI  - Rapid reversible coma with intravenous gamma-hydroxybutyrate in a moxifloxacin
      treated patient.

PMID- 17532700
TI  - Amlexanox for the treatment of recurrent aphthous ulcers.
AB  - Recurrent aphthous ulcer (RAU) is the most prevalent oral mucosal disease in
      humans, estimated to affect between 5% and 50% of the general population. The
      minor manifestation of the condition is the most common and is characterised by
      small, shallow, round or oval lesions that are surrounded by a raised
      erythematous halo and are covered by a grey-white pseudomembrane. Appropriate
      management of patients with this condition is largely symptomatic and should
      focus on reducing ulcer duration, relieving pain and reducing or preventing ulcer
      recurrence. Amlexanox is a novel anti-inflammatory and anti-allergic agent that
      has been evaluated for the treatment of RAU in a series of robust clinical
      trials. After a 100mg dose of 5% amlexanox topical paste, applied directly to the
      lesion, the maximum serum concentration of the drug was 120 ng/mL, which was
      achieved 2.4 hours after application. Steady-state concentrations were achieved
      within 1 week of starting four times daily dosing and there was no evidence of
      accumulation. In terms of efficacy, application of 5% amlexanox topical paste was
      shown to consistently and significantly accelerate complete ulcer healing and the
      time to resolution of pain across four large efficacy studies. Significantly more
      patients had completely healed ulcers from day 3 (compared with no treatment) and
      day 4 (compared with vehicle). Healing was mirrored by an improvement in pain:
      significantly more patients had complete resolution of pain from day 2 (compared
      with no treatment) and day 3 (compared with vehicle). Overall, amlexanox was well
      tolerated, with a low frequency of adverse effects. In the oral application
      studies, adverse effects that were considered by investigators to be potentially
      related to the study treatment occurred in 2.4% and 2.1% of 5% amlexanox and
      vehicle recipients, respectively. These effects were mainly local and were all
      classed as mild to moderate in severity, with the exception of one case of severe
      stinging in the vehicle treatment group. Furthermore, the incidence of dermal
      irritation and sensitisation was very low with amlexanox. These findings suggest
      that 5% amlexanox topical paste is a useful and well tolerated therapeutic option
      for the treatment of RAU.

PMID- 17532701
TI  - Amlodipine Besylate versus Candesartan Cilexetil in Hypertensive Patients -
      Office and Self-Measured Blood Pressure : A Randomised, Double-Blind,
      Comparative, Multicentre Trial.
AB  - OBJECTIVE: The aim of this study was to compare the antihypertensive efficacy and
      tolerability of the calcium channel antagonist amlodipine besylate versus the
      angiotensin II type 1 receptor antagonist candesartan cilexetil in hypertensive
      patients. PATIENTS AND METHODS: After a 2-week placebo washout period, 326
      patients with essential hypertension were randomised to receive amlodipine 5mg
      once daily or candesartan cilexetil 8mg once daily in a double-blind, parallel
      group design with a 12-week active treatment period followed by a 4-day placebo
      drug-free period. The initial daily dose could be doubled at week 6 if office
      diastolic blood pressure (DBP) was still >/=90mm Hg. BP changes were assessed
      daily through patient self-measurements, and fortnightly by office BP
      measurements. RESULTS: A total of 294 patients (151 amlodipine and 143
      candesartan cilexetil) were included in the per-protocol analysis of the primary
      endpoint of BP change from baseline at 12 weeks. Reductions in sitting office
      systolic BP (SBP) [amlodipine 24.4mm Hg, candesartan cilexetil 22.3mm Hg] and DBP
      (amlodipine 14.9mm Hg, candesartan cilexetil 14.8mm Hg) were statistically
      equivalent within the chosen range of equivalence (5mm Hg for SBP and 3mm Hg for
      DBP). The proportion of controlled patients (office BP <140/90mm Hg) at the end
      of therapy was similar in both treatment groups (amlodipine 46.9%, candesartan
      cilexetil 44.4%). The reduction in self-measured DBP was significantly greater (p
      < 0.05) for amlodipine (7.2mm Hg) compared with candesartan cilexetil (4.8mm Hg).
      There was no significant difference between the two treatments in the incidence
      of adverse events reported. CONCLUSIONS: Amlodipine besylate and candesartan
      cilexetil were both very effective in lowering office BP after 12 weeks of
      treatment. There was a trend towards a better self-measured BP reduction with
      amlodipine compared with candesartan cilexetil. The overall incidence of adverse
      events was comparable between the two treatments.

PMID- 17532702
TI  - Safety and tolerability of acarbose in the treatment of type 1 and type 2
      diabetes mellitus.
AB  - OBJECTIVE: To assess the safety profile of acarbose treatment over a 1-year
      period at a dose range of 50-300mg three times daily in patients with type 1 or
      type 2 diabetes mellitus. STUDY DESIGN AND PATIENTS: In this 56-week, double
      blind, parallel-group, multicentre comparison, patients were randomised to
      acarbose or placebo in a 2 : 1 ratio. An 8-week forced titration phase (from 50
      300mg three times daily) was followed by a 48-week maintenance phase during which
      patients received the highest dose tolerated during titration. Patients were
      assessed at 13 visits with respect to adverse events/intercurrent illnesses,
      abnormal laboratory values (serum chemistry, urinalysis, complete blood and
      reticulocyte count, serum iron and total iron binding capacity, and serum vitamin
      B(6), B(12), D and folate levels), discontinuation rates, ECG findings, vital
      signs and evaluation of the patients' diaries with regard to gastrointestinal
      events. A total of 359 patients (acarbose 240, placebo 119) were valid for
      analysis; 21% had type 1 diabetes. Most patients received concomitant insulin or
      sulfonylurea treatment. RESULTS: Study withdrawal was reported for 35% of
      acarbose and 24% of placebo recipients (p = 0.053); adverse events were the main
      reason for withdrawal in acarbose recipients (20%; placebo group 5%; p < 0.01).
      The most common adverse events for acarbose recipients were gastrointestinal
      (abdominal pain, flatulence and diarrhoea), which were more frequent than in
      placebo patients (p < 0.01). These events occurred more often early in the study
      and attenuated over time. CONCLUSION: Acarbose was safe and well tolerated by the
      majority of diabetic patients over a 1-year treatment period.

PMID- 17532703
TI  - Long-term efficacy and tolerability of acarbose treatment in patients with type 2
      diabetes mellitus.
AB  - OBJECTIVE: The aim of the study was to investigate the efficacy and tolerability
      of long-term acarbose therapy in type 2 diabetic patients. STUDY DESIGN: In this
      double-blind, single-centre group comparison, patients were randomised to receive
      either acarbose or matching placebo, in addition to their regular antidiabetic
      therapy, over a period of 78 weeks. Eligibility for inclusion in the efficacy
      evaluation included a study duration of >/=510 days. METHODS: The primary
      efficacy parameter was the change in glycosylated haemoglobin (HbA(1)) from
      baseline to end of study. Secondary variables included changes in blood glucose
      and lipid parameters, as well as signs of retinopathy and nephropathy. PATIENTS:
      A total of 139 patients were assessed for safety and 88 patients (44 in each
      treatment group) were included in the efficacy analysis. Patients were generally
      overweight and the majority had previously been treated with sulphonylureas.
      RESULTS: Acarbose significantly improved fasting and 1-hour postprandial blood
      glucose levels compared with placebo (p = 0.039 and 0.009), and improvements in
      HbA(1) with acarbose versus placebo fell just short of significance (p = 0.057).
      There were no differences between treatments in changes in microvascular
      complications, but blood pressure improved with acarbose treatment. Two patients
      in the acarbose group experienced elevated liver enzyme levels. Generally,
      acarbose had a good safety profile and was well tolerated. CONCLUSION: Long-term
      treatment with acarbose was safe and efficacious in patients with type 2 diabetes
      mellitus that was insufficiently controlled by other oral antidiabetics.

PMID- 17532704
TI  - Economic Evaluation of a New Antiemetic Drug - Palonosetron versus Ondansetron :
      Assessment of the Drug Price Ratio in Five European Countries.
AB  - OBJECTIVES: This study aimed to identify, measure and evaluate expected costs of
      innovative palonosetron-based antiemetic therapy versus ondansetron-based
      treatment, the ultimate aim being to measure the drug price ratio (DPR) of the
      two pharmacological treatments in five different European countries. METHODS: A
      decision model compared two antiemetic treatments - palonosetron and ondansetron 
      in terms of expected costs of emesis management from a hospital perspective. The
      model was compiled for 374 patients. The clinical superiority of palonosetron in
      preventing acute and delayed emesis, measured in terms of: (i) complete response
      rates, (ii) number of emetic episodes, and (iii) administration of rescue
      medication, was derived from a previously published clinical trial. The cost data
      were gathered through economic questionnaires distributed in 11 European hospital
      centres. The expected costs of emesis management with palonosetron and
      ondansetron at ondansetron prices were used to calculate the DPR for palonosetron
      in each of the five European countries. RESULTS: In the baseline analysis, DPR
      varied from 1.55 (in Russia) to 2.60 (in the UK). The sensitivity analysis of the
      unit costs of emetic episodes and rescue medication identified a range from 1.39
      (in Germany) to 4.09 (in Russia). Even in the least favourable clinical scenario,
      palonosetron was a preferred antiemetic strategy with a DPR >1 in all five
      countries. CONCLUSIONS: This is the first economic evaluation analysis of
      palonosetron. The results demonstrate that palonosetron, because of its superior
      clinical efficacy in controlling emesis, could have a favourable DPR when
      compared with ondansetron in all five countries considered and still offer lower
      or equal net treatment costs for the hospital.

PMID- 17532705
TI  - Patients' perception of the value of levocetirizine in allergic diseases : a
      multicentre observational study in Germany.

PMID- 17532706
TI  - Long-Term 'Self-Managed' Immunosuppressive Treatment Resulting in Death due to
      Fulminant Hepatitis B : Medical Malpractice or Patient's Autolesionism?

PMID- 17532707
TI  - Fluoroquinolone therapy for uncomplicated skin and skin structure infections : a
      retrospective database comparison of treatment duration, failures and charges.
AB  - OBJECTIVE: Uncomplicated skin and skin structure infections (uSSSIs) are highly
      prevalent and costly. With the rising prevalence of bacterial resistance to older
      antibacterials, there has been an increase in the use of fluoroquinolones for the
      treatment of uSSSIs creating the need for comparative information. The objective
      of this study was to compare, under real-world conditions, the treatment
      duration, failure rates and treatment charges associated with initiation of
      outpatient treatment for uSSSIs with moxifloxacin versus levofloxacin. METHODS:
      This retrospective study was conducted using claims data (April 1999 through
      March 2002) from the PharMetrics Patient-Centric Database. A cohort was created
      of patients who had treatment for a uSSSI that was initiated with either
      moxifloxacin or levofloxacin. The endpoints evaluated were: treatment duration,
      treatment failure and total charges. Logistic and ordinary least-squares
      regression analyses were used to test for differences among treatment groups
      whilst controlling for demographic and clinical characteristics. RESULTS: 506
      patients were identified, representing 517 uSSSI treatment episodes. The mean
      durations of monotherapy and all antibacterial prescription therapy were
      significantly shorter for the moxifloxacin than the levofloxacin group
      (differences of 1.97 days [p = 0.015] and 1.60 days [p = 0.036], respectively).
      The original prescription duration, treatment failure rate and treatment charges
      were lower for the moxifloxacin group than the levofloxacin group, but
      differences were not statistically significant (p = 0.241, 0.395 and 0.199,
      respectively). CONCLUSION: In general, patients who initiated therapy for a uSSSI
      with moxifloxacin had a shorter duration of antibacterial therapy than those who
      initiated treatment with levofloxacin, with comparable treatment failure and cost
      outcomes. When a fluoroquinolone is required for the treatment of a uSSSI, moxi-
      floxacin (which is approved for 7-day therapy) provides comparable outcomes to
      levofloxacin under real-world conditions.

PMID- 17532708
TI  - Pilot study of on-demand therapy with pantoprazole 20mg for long-term treatment
      in patients with mild gastro-oesophageal reflux disease.
AB  - BACKGROUND: Few clinical studies have demonstrated the efficacy of proton pump
      inhibitors (PPIs) as on-demand therapy for the long-term management of patients
      with mild gastro-oesophageal reflux disease (GORD). On-demand therapy with
      pantoprazole 20mg may offer an effective strategy for the management of mild
      GORD. METHODS: Patients with mild GORD grade 0 or 1 and heartburn of at least
      moderate intensity at the start of the study were treated with pantoprazole 20mg
      once daily for 28 days (n = 254). Patients with no heartburn during the final 3
      days of the acute treatment phase entered the long-term treatment phase and took
      pantoprazole 20mg on demand for 6 months. Antacids were provided as rescue
      medication during this phase. The primary endpoint was the percentage of patients
      unwilling to continue the study because of insufficient control of symptoms. In
      addition, the intensities and the relapse rates for heartburn, acid eructation
      and epigastric pain were determined. RESULTS: At the end of the acute treatment
      phase, 234 of 254 patients (92.1%) were free from heartburn and entered the long
      term treatment phase (intention-to-treat [ITT]). The time until study
      discontinuation because of inadequate control of heartburn during the on-demand
      treatment phase ranged from 9 to 147 days. In the ITT population, only 2.8% of
      patients were unwilling to continue the study because of insufficient heartburn
      control. Relapse rates were 4.3% for heartburn, 2.3% for acid eructation and 1.0%
      for epigastric pain. After 6 months of on-demand treatment, 82% of patients
      stated that improvements in their symptoms were maintained. For symptom control
      during the on-demand phase, patients took one tablet of pantoprazole 20mg every
      2.3 days. Additionally, patients took one magaldrate tablet every 2.4 days.
      CONCLUSION: Results of this pilot study show that on-demand therapy with
      pantoprazole 20mg appears to be an effective treatment strategy for the long-term
      treatment of mild GORD. Treatment acceptance by patients was high.

PMID- 17532709
TI  - In vivo comparative pharmacokinetics and pharmacodynamics of moxifloxacin and
      levofloxacin in human neutrophils.
AB  - OBJECTIVE: Most of the newer fluoroquinolones are active against bacteria such as
      Streptococcus pneumoniae and Staphylococcus aureus, which are able to multiply
      inside polymorphonuclear leukocytes (PMNs). The aim of this study was to
      determine moxifloxacin and levofloxacin intracellular behaviour with their usual
      dosage regimen. METHODS: We determined the pharmacokinetics of moxifloxacin and
      levofloxacin at steady state in the PMNs of ten healthy volunteers receiving
      moxifloxacin 400mg and levofloxacin 500mg as a once-daily dosing regimen for 3
      days. RESULTS: Both antibacterials showed a high level of intracellular
      penetration exhibiting PMNs/plasma ratios of 17.34 +/- 8.29 for moxifloxacin
      versus 8.15 +/- 5.23 for levofloxacin for maximum concentrations (C(max)) and
      14.72 +/- 8.29 for moxifloxacin versus 8.15 +/- 5.23 for levofloxacin for the
      area under the plasma concentration-time curve. Estimation of the most predictive
      pharmacodynamic surrogate markers for concentration-dependent bactericidal
      antibacterials in the intracellular milieu by taking into account the
      susceptibility of S. pneumoniae and methicillin-susceptible S. aureus
      demonstrated consistently higher values with moxifloxacin than with levofloxacin,
      even though with both drugs the levels obtained are well above the recommended
      targets values. Indeed, C(max)/MIC ratios calculated in PMNs for moxifloxacin
      were 287.3 and 718.2 for S. pneumoniae and S. aureus, respectively, and for
      levofloxacin were 25.6 and 205.1, respectively. CONCLUSION: Moxifloxacin and
      levofloxacin seem to be well adapted for the treatment of infections due to
      susceptible intracellular bacteria, and moxifloxacin provides a greater margin of
      safety than levofloxacin.

PMID- 17532710
TI  - Evaluation of the efficacy and tolerability of acarbose in patients with diabetes
      mellitus : a postmarketing surveillance study.
AB  - OBJECTIVE: The efficacy and tolerability of acarbose were examined in a
      postmarketing surveillance study of 27 803 patients with diabetes mellitus (26
      044 were diagnosed as having type 2 diabetes) over a 12-week treatment period.
      PATIENTS AND M ethods: Overall efficacy data were reported for type 1 and type 2
      diabetes, and a detailed data analysis was conducted for patients with type 2
      diabetes. Tolerability was described for the total group. Of the type 2 diabetes
      patients, 37.6% were treated with diet only; 44.2% were additionally treated with
      sulphonylureas; 6.3% with metformin or metformin plus sulphonylurea; and 11.6%
      with insulin alone or in combination with oral treatment. The frequency of two or
      more concomitant diseases was 45.8% for all type 2 diabetes patients, and 62.4%
      in elderly patients (age >/=70 years). RESULTS: In patients with type 2 diabetes,
      acarbose administration in addition to the existing treatment resulted in
      reductions in mean blood glucose levels (fasting 50 mg/dL, 1h post-prandial [pp]
      60 mg/dL, 2h pp 56 mg/dL), glycosylated haemoglobin (HbA(1c) 1.3%; HbA(1) 1.6%)
      and bodyweight (1.5 kg). Results for type 1 diabetes patients were similar. No
      clinically relevant influence of age, body mass index or number of concomitant
      diseases on the results could be observed. Tolerability was good: 83% of patients
      had no adverse events, 13.7% reported flatulence, and 2.2% had at least one
      occurrence of diarrhoea. Hypoglycaemia was found in 0.07% of patients, mainly in
      combination with metformin or insulin. Tolerability was independent of patients'
      age. Laboratory investigations gave no indication of other adverse events.
      CONCLUSION: This postmarketing surveillance study documents the therapeutic
      benefit and good tolerability and compliance of acarbose as mono- and combination
      therapy, even in elderly and multimorbid patients.

PMID- 17532711
TI  - Treatment of Basal Cell Carcinoma Located in the Head and Neck Region with
      Intralesional Interferon alpha-2a : Evaluation of Long-Term Follow-Up Results.
AB  - OBJECTIVE: Intralesional injections of interferon have been reported to provide
      successful results in the treatment of basal cell carcinoma. However, there are
      only a few reports describing the long-term efficacy of this therapy. The aim of
      our study was to evaluate the efficacy and long-term results of interferon alpha
      2a (IFNalpha-2a) in the treatment of basal cell carcinoma. METHODS: Twenty
      dermatopathologically proven basal cell carcinoma lesions were treated with
      intralesional IFNalpha-2a injections three times weekly for 3 weeks. The dose per
      injection was 1.5 x 10(6)IU if the lesion was <2cm in diameter and 3.0 x 10(6) IU
      if it was >/=2cm. Eight weeks after the last injection, the lesion sites were
      rebiopsied and all cases were reevaluated both clinically and
      dermatopathologically. Patients with complete cure were followed up for 7 years
      to determine the long-term results. RESULTS: Eleven lesions (55%) showed complete
      clinical and dermatopathological remission, six lesions (30%) showed partial
      remission, and two lesions (10%) showed no response. One lesion (5%) increased in
      size during the treatment. No serious adverse effects were observed. During the
      follow-up period there was only one recurrence, at the fifth year. CONCLUSION:
      Treatment with intralesional IFNalpha-2a was shown to be an effective therapeutic
      option for basal cell carcinoma, with low recurrence rates in long-term follow
      up.

PMID- 17532712
TI  - Simulated fluctuations in plasma drug concentrations for patients receiving
      oxcarbazepine or carbamazepine extended-release capsules.

PMID- 17532713
TI  - Fatal anaphylactic reaction to intravenous cephalexin.

PMID- 17532714
TI  - Overview of clinical trials in the treatment of iron deficiency with iron-acetyl
      aspartylated casein.
AB  - Iron therapy is necessary in a wide variety of clinical situations, and new
      formulations with improved tolerability and efficacy would be a welcome
      alternative to ferrous sulfate. A trivalent iron protein complex has been
      developed using an N-acetyl-aspartylated derivative of casein (Fe-ASP) for oral
      iron therapy. This paper provides an overview of the pharmacokinetic and clinical
      data on Fe-ASP use. To date, 704 paediatric and adult patients affected by iron
      deficiency anaemia with a wide variety of clinical histories (dietary, iron
      absorption defects, pregnancy, chronic or acute gastrointestinal haemorrhage)
      have been treated with Fe-ASP in 16 clinical trials including nine open and seven
      controlled trials. In healthy volunteers, Fe-ASP proved to be an efficient
      vehicle for providing iron with high bioavailability and more rapid and
      persistent increases in serum iron levels than ferritin. In open clinical trials,
      highly significant improvements in clinical and haematological parameters were
      observed after treatment with Fe-ASP in all categories of patients with iron
      deficiency anaemia. In controlled clinical trials, the changes in clinical and
      haematological profiles observed with Fe-ASP were virtually identical to those
      seen with iron protein succinylate (IPS), and Fe-ASP also compared well with
      parenteral iron gluconate. No safety considerations were raised.Fe-ASP shows high
      efficacy in iron-deficient anaemia treatment, and it is an extremely well
      tolerated iron vehicle. Fe-ASP represents a valid alternative to IPS and shows
      promise as a substitute for parenteral iron therapy in selected clinical
      situations.

PMID- 17532715
TI  - Efficacy and tolerability of sequential intravenous/oral moxifloxacin therapy in
      pneumonia: results of the first post-marketing surveillance study with
      intravenous moxifloxacin in hospital practice.
AB  - OBJECTIVE: This study aimed to investigate the efficacy, safety and tolerability
      of sequential intravenous (IV)/oral therapy with moxifloxacin in pneumonia under
      general hospital treatment conditions. PATIENTS AND METHODS: Patients with
      pneumonia were documented in this non-interventional multicentre study. The
      patients were treated with IV moxifloxacin or moxifloxacin sequential therapy (IV
      and oral) in hospitals throughout Germany. Exclusion criteria were limited to the
      contraindications mentioned in the summary of product characteristics. The
      participating hospital-based physicians documented the patients' demography,
      anamnesis, antibiotic pretreatment, concomitant diseases and medications.
      Moxifloxacin therapy and symptom status were recorded daily up to the ninth day
      and on the last day of treatment. The physicians assessed the efficacy and
      tolerability of IV moxifloxacin therapy and reported all adverse events observed
      within the treatment period. RESULTS: The 1749 documented patients had a mean age
      of 66.2 (SD 15.5) years; 56.4% were males and 43.5% females. The majority (99.3%)
      were treated with moxifloxacin 400mg once daily. On average, moxifloxacin was
      given for 7.6 days (SD 3.2). In cases of sequential therapy (78.9% of patients),
      IV moxifloxacin was switched to oral moxifloxacin after a mean of 4.1 days (SD
      1.8). Moxifloxacin produced a significant clinical improvement in 58.2% of
      patients by day 3 of therapy, in 84.2% by day 5 and in 89.4% by day 7. Recovery
      occurred in 27.0% of patients by day 5, in 54.0% by day 7 and in 87.0% by day 14.
      It took a mean of 3.4 days (SD 1.9) until improvement and 7.2 days (SD 3.0) until
      cure. Overall efficacy of IV moxifloxacin therapy was rated by the physicians as
      'very good' or 'good' in 82.9% of patients. Tolerability was rated in 94.3% of
      patients as 'very good' or 'good'. Adverse events were recorded for 92 (5.3%)
      patients, but events were considered by the attending physician to be related to
      moxifloxacin therapy for only 45 patients (2.6%). CONCLUSIONS: IV moxifloxacin
      shows high efficacy in the treatment of pneumonia under routine clinical
      treatment conditions. IV moxifloxacin relieves pneumonia-associated symptoms
      rapidly and allows an early switch to oral administration. Because of its high
      efficacy and very good safety and tolerability profile, moxifloxacin delivers
      excellent benefits as first-line therapy for pneumonia.

PMID- 17532716
TI  - Effects of rice policosanol on serum lipoproteins, homocysteine, fibrinogen and C
      reactive protein in hypercholesterolaemic patients.
AB  - BACKGROUND: Policosanol is an agent that includes mixtures of aliphatic primary
      alcohols extracted primarily from sugar-cane wax. This mixture has been shown to
      lower total and low-density lipoprotein (LDL) cholesterol in animal models,
      healthy volunteers and hypercholesterolaemic patients. PATIENTS AND METHODS: This
      study investigated the efficacy and tolerability of rice policosanol (Oryza sp.)
      10 mg/day in 70 hypercholesterolaemic patients of both sexes aged 20-78 years in
      a randomised, double-blind, crossover, placebo-controlled, single-centre trial.
      After an 8-week run-in period during which patients were placed on therapeutic
      lifestyle changes, in particular a cholesterol-lowering diet, they were randomly
      assigned to receive rice policosanol 10mg tablets or placebo tablets once daily
      with the evening meal for 8 weeks. During the next 8 weeks those patients who
      received policosanol during the first 8 weeks received placebo, and those who
      received placebo during the first 8 weeks, received policosanol. Total, LDL, high
      density lipoprotein (HDL), HDL2 and HDL3 cholesterol, triglycerides, oxidised LDL
      (ox-LDL), apoproteins (Apos) AI and B, lipoprotein (a) [Lp(a)], fibrinogen,
      homocysteine and C-reactive protein (CRP) levels were measured. RESULTS: Rice
      policosanol significantly reduced plasma total cholesterol from 7.37 +/- 1.42
      mmol/L to 6.99 +/- 1.33 mmol/L (p = 0.007) and increased Apo AI from 1.49 +/-
      0.39 mmol/L to 1.58 +/- 0.38 mmol/L (p = 0.037) but did not change plasma
      triglycerides, HDL, HDL2, HDL3 and LDL cholesterol, ox-LDL, Lp(a), Apo B,
      fibrinogen, homocysteine or CRP levels. CONCLUSION: Rice policosanol 10 mg/day
      moderately decreased plasma total cholesterol and increased Apo AI. Rice
      policosanol was also well tolerated, with no drug-related effects on safety
      parameters such as serum aminotransferases and creatine phosphokinase detected or
      found on physical examination.

PMID- 17532717
TI  - High prevalence and undertreatment of hypercholesterolaemia in participants in a
      public stroke prevention programme in austria.
AB  - BACKGROUND: There is remarkable consistency in large cohort studies regarding the
      relationship between serum cholesterol and the incidence of coronary heart
      disease (CHD), and increasing interest in the relationship between serum
      cholesterol and stroke. The aim of our investigation was to identify the
      prevalence and control of hypercholesterolaemia in participants in a public
      stroke prevention programme. PATIENTS AND METHODS: 9274 participants were
      categorised according to the guidelines of the National Cholesterol Education
      Program-Adult Treatment Panel III (NCEP-ATP III) and analysed with reference to
      risk category, treatment eligibility and treatment quality. RESULTS: NCEP-ATP III
      identifies low-density lipoprotein (LDL) cholesterol as the primary target of
      treatment. In this programme, 499 (5.4%) subjects were classified as having
      optimal (<100 mg/dL) LDL cholesterol levels, 1718 (18.5%) as near optimal (100
      129 mg/dL), 2863 (30.9%) as borderline high (130-159 mg/dL), 2472 (26.7%) as high
      (160-189 mg/dL) and 1722 (18.6%) as very high (>190 mg/dL). 4442 (47.9%)
      participants presented with 0-1 risk factors, 2451(26.4%) with multiple (2+) risk
      factors, and 2381 (25.7%) met the criteria of secondary prevention. The suggested
      treatment goals were met in 2411 (54.3%) participants with 0-1 risk factors, in
      561 (22.9%) of the multiple-risk-factor group, and in 148 (6.2%) subjects with
      established CHD or risk equivalents. A total of 871 subjects (9.4%) reported use
      of cholesterol-lowering drugs. CONCLUSIONS: We observed a considerable prevalence
      and poor control of hypercholesterolaemia in participants in a public stroke
      prevention programme in Austria.

PMID- 17532718
TI  - Cost Effectiveness of Cardioprotective Strategies in Patients with Aggressive Non
      Hodgkin's Lymphoma.
AB  - OBJECTIVE: The cardiotoxicity of anthracyclines remains a key problem in patients
      with aggressive non-Hodgkin's lymphoma (NHL). With regard to the actual long-term
      prognosis of aggressive NHL, the development of cardioprotective strategies is
      mandatory for these patients. A cost-effectiveness analysis was carried out to
      determine the potential economic profile of dexrazoxane or liposome-encapsulated
      doxorubicin in patients with aggressive NHL treated with a CHOP regimen
      (cyclophosphamide, doxorubicin, vincristine, prednisone) as first-line therapy.
      METHODS: A decision-analysis model described clinical events and economic
      consequences for theoretical patients who were to receive eight consecutive
      cycles of a CHOP regimen containing 50 mg/m(2) of doxorubicin as first-line
      chemotherapy. The timeframe of the model was the patient's lifetime. The
      probabilities were related to the cumulative dose of doxorubicin and age. The
      study was carried out from the perspective of the French healthcare system.
      Patients entered the model at 'choose' node: no cardioprotection versus
      cardioprotection with dexrazoxane or liposome-encapsulated doxorubicin. The model
      was based on a retrospective epidemiological study and on published data. The
      clinical end-point was life expectancy. Direct medical costs related to the
      cardioprotection and the treatment of congestive heart failure were considered.
      Monetary values for French prices in the year 2002 were used. Several univariate
      sensitivity analyses were carried out with varying clinical and economic
      parameters. RESULTS: Per 100 patients, the two cardioprotective strategies
      provided similar benefits that were estimated as 24.5 and 13.4 life-years in 60-
      and 40-year-old patients, respectively. The cost per life-year saved with
      dexrazoxane was estimated as euro6931 and euro15 599 in 60- and 40-year-old
      patients, respectively, and euro22 940 and euro44 982, respectively, with
      liposome-encapsulated doxorubicin. Several sensitivity analyses showed the
      robustness of the model. CONCLUSION: The results suggest the potential clinical
      and economic usefulness of cardioprotective therapies in patients with aggressive
      NHL. Prospective studies are needed to confirm these findings.

PMID- 17532720
TI  - [Not Available].

PMID- 17532719
TI  - Lack of Pharmacokinetic Interaction between Esomeprazole and the Nonsteroidal
      Anti-Inflammatory Drugs Naproxen and Rofecoxib in Healthy Subjects.
AB  - BACKGROUND: We investigated the potential interactions between esomeprazole and a
      non-selective nonsteroidal anti-inflammatory drug (NSAID; naproxen) or a cyclo
      oxygenase (COX)-2-selective NSAID (rofecoxib) in healthy subjects. METHODS: Two
      studies of identical randomised, open, three-way crossover design were conducted.
      Subjects (n = 32 for both studies) were to receive 1 week's treatment with
      esomeprazole 40mg once daily (studies A and B), naproxen 250mg twice daily (study
      A), rofecoxib 12.5mg once daily (study B), and esomeprazole in combination with
      naproxen (study A) or rofecoxib (study B). Study periods were separated by a 2
      week washout period. RESULTS: On day 7 of dosing, the ratios (and 95% CIs) for
      the area under the plasma concentration-time curve during the dosing interval
      (AUC(tau)) and observed maximum plasma concentration (C(max)) of esomeprazole and
      NSAID combination/NSAID alone were 0.98 (0.94, 1.01) and 1.00 (0.97, 1.04),
      respectively, for study A, and 1.15 (1.06, 1.24) and 1.14 (1.02, 1.28),
      respectively, for study B. The ratios (and 95% CIs) for AUC(tau) and C(max) of
      esomeprazole and NSAID combination/esomeprazole alone were 0.96 (0.89, 1.03) and
      0.92 (0.85, 1.00), respectively, for study A, and 1.05 (0.96, 1.15) and 1.05
      (0.94, 1.18), respectively, for study B. All treatments were well tolerated
      during the study period. CONCLUSION: Naproxen and rofecoxib do not interact with
      esomeprazole, and esomeprazole does not affect the pharmacokinetics of naproxen
      or rofecoxib. These findings indicate that esomeprazole can be used in
      combination with NSAIDs without the risk of a pharmacokinetic interaction.

PMID- 17532721
TI  - Insomnia in general practice : a consensus report produced by sleep specialists
      and primary-care physicians in Italy.
AB  - Insomnia is an extremely common condition with major social and economic
      consequences worldwide. Two large epidemiological studies (Morfeo 1 and Morfeo 2)
      recently performed in Italy provided much-needed novel data on the impact of
      insomnia in patients whose primary healthcare is provided by general
      practitioners (GPs). These studies found that insomnia is managed relatively well
      by GPs in Italy, although diagnosis and treatment can be compromised because of
      the lack of standardised criteria. Although a number of consensus reports on
      insomnia have been published, these are mainly highly specific documents that are
      difficult to implement in general practice. To address this, a consensus group
      involving 695 GPs and over 60 specialists from the Italian Association of Sleep
      Medicine was established. The major objectives of the consensus study were to
      establish basic knowledge for the diagnosis and treatment of insomnia, and to
      produce guidelines for the management of insomnia by GPs. This is the first time
      that GPs have been directly involved in producing insomnia guidelines of this
      type, and this approach reflects their pivotal role in the diagnosis and
      management of this condition. Participants were carefully selected to ensure
      adequate representation of sleep specialists and GPs, with the group being headed
      by a steering committee and an advisory board. Guideline statements were selected
      following careful literature review and were voted on using formalised consensus
      procedures. This review describes current views on the diagnosis and management
      of insomnia from the perspective of the GP. In addition, the results of the
      consensus study are presented. They include recognition of the following
      principles: (i) insomnia is a genuine pathology that must be appropriately
      diagnosed and treated; (ii) when concomitant pathologies are present, additional
      significance should be given to treatment of insomnia since it can influence
      prognosis of coexistent disorders; (iii) appropriate treatment should consider
      the cause of insomnia as well as the characteristics of available pharmacological
      agents; (iv) with regard to hypnotic drugs, preference should be given to
      medications with a short half-life in order to limit residual effects; (v) non
      benzodiazepine hypnotics are preferred to classic benzodiazepines as they have
      higher selectivity and present a lower risk of undesirable effects; (vi) tablets
      are preferable to liquid preparations as they are less likely to lead to
      dependence and to overdosing by the patient; and (vi) once treatment has been
      initiated, insomnia patients should be carefully followed up. These statements
      provide much needed criteria for better management of insomnia by GPs in Italy.

PMID- 17532722
TI  - Antihypertensive effect of irbesartan and predictors of response in obesity
      associated hypertension : a prospective, open-label study.
AB  - BACKGROUND: Obesity-associated hypertension is difficult to treat and puts
      patients at a substantially increased risk of cardiovascular events. Irbesartan
      has previously been shown to effectively lower blood pressure (BP) in high-risk
      groups including patients with type 2 diabetes mellitus or nephropathy, and may
      therefore also be suitable for the treatment of obesity-associated hypertension.
      In this study we aimed to: (a) assess the efficacy and tolerability of irbesartan
      alone and in combination with hydrochlorothiazide in patients with obesity
      associated mild-to-moderate hypertension; and (b) investigate patient-associated
      determinants of poor BP control in this patient group. PATIENTS AND METHODS: This
      was a 3-month, prospective, open-label, multicentre, phase IV study in 72 479
      hypertensive patients in 6989 general practices across Germany. Main outcome
      measures were BP reduction (primary parameter of effectiveness) and BP response
      rates after 3 months, as well as adverse events (AEs). Independent predictors of
      poor control were identified in a multivariate proportional odds model. RESULTS:
      All of the patients were Caucasian, 50.5% were females, mean age was 62.1 +/-
      11.1 years, mean bodyweight was 88.6 +/- 15.4kg, and mean body mass index (BMI)
      was 30.7 +/- 4.8 kg/m(2). Almost all the patients were overweight or obese
      (92.3%). From a baseline value of 162/94mm Hg, systolic and diastolic BP were
      reduced by a mean of -23/-12mm Hg after 3 months. 66.1% of the patients were
      responders (reduction of diastolic BP >/=10mm Hg), and 48.0% achieved BP
      normalisation (i.e. <140/90mm Hg). 79% of patients met their individual treatment
      goals as defined by the treating physician (mean 135/80mm Hg). AEs were reported
      in only 322 patients (0.4%). Factors requiring special attention in patients not
      achieving BP control were age (>55 years), high BMI category (>25 kg/m(2)), and
      increased waist circumference. CONCLUSION: Treatment with irbesartan (+/-
      hydrochlorothiazide) appeared to be effective and well tolerated in the study
      population of patients with obesity- associated hypertension. Easily recognisable
      characteristics allow physicians to identify patients whose BP is likely to be
      difficult to control.

PMID- 17532723
TI  - Effects of cilnidipine on fibrinolysis in chinese hypertensive patients.
AB  - BACKGROUND: Hypertension is an important risk factor for myocardial infarction
      and stroke. Accumulating data support the association of blood pressure and
      impairment of fibrinolysis in hypertensive patients. Fibrinolysis plays a pivotal
      role in atherogenesis, but there are few studies that focus on evaluating the
      effect of calcium channel antagonists on fibrinolysis in hypertensive patients,
      and the results are controversial. The aim of this study was therefore to
      investigate the effects of cilnidipine on fibrinolysis in Chinese hypertensive
      patients. METHODS: This study was an open-label, paired trial that included 43
      patients with mild-to-moderate hypertension. After a 2-week placebo washout
      period, patients were treated with cilnidipine 5mg daily for 8 weeks. Venous
      blood was taken before and after treatment between 8am and 9am, after an
      overnight fast. Plasma tissue plasminogen activator (tPA) antigen and plasminogen
      activator inhibitor type 1 (PAI-1) antigen were measured by ELISA and plasma
      angiotensin II was measured by radioimmunoassay. RESULTS: After treatment with
      cilnidipine for 8 weeks, plasma tPA antigen level increased significantly (from
      12.12 +/- 6.77 ng/mL pre-treatment to 16.12 +/- 11.89 ng/mL post-treatment, p <
      0.05), and the PAI-1 antigen level remained unaffected. There were no significant
      changes in plasma angiotensin II. Systolic and diastolic blood pressures were
      significantly decreased without changes in heart rate. CONCLUSIONS: These data
      suggest that in hypertensive patients, a population with impaired fibrinolysis,
      cilnidipine may improve the fibrinolytic balance, and that cilnidipine is
      effective in treating hypertension without causing reflex tachycardia.

PMID- 17532725
TI  - Famciclovir for the management of genital herpes simplex in patients with
      inadequate response to aciclovir or valaciclovir.

PMID- 17532724
TI  - Economic evaluation of tramadol/paracetamol combination tablets for
      osteoarthritis pain in the Netherlands.
AB  - OBJECTIVE: To compare the costs of treating osteoarthritis (OA) pain using
      combination tramadol/paracetamol tablets, NSAIDs alone, NSAIDs plus proton pump
      inhibitors (PPIs), or NSAIDs plus histamine H(2)-receptor antagonists (H(2)RAs)
      from the perspective of the Dutch healthcare system. DESIGN AND METHODS: A
      decision-analytical model was constructed to model the cost outcomes of the four
      treatment strategies over 6 months. A cost-minimisation approach was used, which
      considered data related to resource utilisation, medication costs and costs for
      the treatment of adverse events. Data, derived mainly from the clinical
      literature, were supplemented by inputs from a Delphi panel as well as official
      price and tariff lists. The base-case analysis considered direct medical costs,
      including those for treating all adverse events with tramadol/paracetamol and
      gastrointestinal (GI) adverse events with NSAIDs. Separate scenario analyses
      explored costs of NSAID-based regimens: (i) according to 21 levels of risk for GI
      adverse events, and (ii) when renal events attributable to NSAIDs were
      considered. Robustness of the model was tested using univariate sensitivity
      analysis. RESULTS: In the base-case analysis, costs for 6 months' treatment of OA
      pain using tramadol/paracetamol were euro244.45, compared with euro317.32 for
      NSAIDs + PPIs, euro200.67 for NSAIDs + H(2)RAs, and euro125.86 for NSAIDs alone.
      This provided a cost saving of euro72.87 per patient over 6 months for
      tramadol/paracetamol compared with NSAIDs + PPIs. Tramadol/paracetamol became
      cost saving compared with NSAIDs alone and NSAIDs + H(2)RAs for GI risk levels
      >13 and >10, respectively. When renal adverse events of NSAIDs were con- sidered,
      tramadol/paracetamol was cost saving compared with all NSAID-based regimens
      (saving euro228.40 vs NSAIDs, euro418.42 vs NSAIDs + PPIs, and euro302.69 vs
      NSAIDs + H(2)RAs [year of costing 2005]). Sensitivity analysis confirmed the
      model was robust to wide-ranging changes in the value of input parameters.
      CONCLUSION: Tramadol/paracetamol is cost saving compared with NSAIDs + PPIs for
      the treatment of OA pain over a period of 6 months regardless of the risk of GI
      or renal complications. Tramadol/paracetamol is also cost saving compared with
      treatment with NSAIDs alone and NSAIDs + H(2)RAs for patients at medium and high
      risk of GI adverse events and in all cases if considering renal adverse events.
      Despite not being quantified in monetary terms, the lower incidence of adverse
      events with tramadol/paracetamol is a clinical benefit.

PMID- 17532726
TI  - Medical students' perceptions of barriers to training at a rural clinical school.
AB  - INTRODUCTION: In response to concerns about the decreasing rural health
      workforce, the Australian Government has funded a number of clinical schools in
      rural locations across Australia. The University of Melbourne established its
      Rural Clinical School (RCS) in 2000, at Shepparton, population 42,000, 175 km
      north of Melbourne, Victoria. The University of Melbourne also has three
      metropolitan-based clinical schools. Rural clinical schools in Australia
      generally have experienced difficulty in recruiting students. This has also been
      the experience of the University of Melbourne's Shepparton-based RCS. This study
      focuses on student perceptions in an attempt to understand the reasons behind
      this difficulty. METHODS: All medical students at The University of Melbourne
      were sent an internet-based questionnaire and invited to participate in this
      study. The survey included information-gathering questions focused on the
      following areas: demographic details, whether or not the student chose to study
      at the RCS, factors that were of importance to them in selection of a clinical
      school, and the reasons why they did or did not prefer the RCS. Participants were
      asked to rank their three most important issues and were then asked to comment on
      what would make training at the University of Melbourne RCS attractive to them.
      RESULTS: The response rate was 49% (n = 785 of 1599). The most common concerns
      relating to the students' selection of a clinical school were the quality of
      teaching and education at the school, transport and location issues, and patient
      access. Other major issues included the ability to obtain the student's preferred
      internship, family and partner issues, and the lack of incentives, such as
      financial incentives. The most common issues for students who did not chose the
      RCS were of a non-clinical nature, such as family and partner commitments,
      financial issues, and housing commitments. The most common factors students
      identified as making the RCS more attractive to them were greater financial
      support and incentives, demonstrating value-added teaching, and teaching that was
      seen as better than that available in the metropolitan centres, and improvement
      in the flow of information, and promotion of the RCS's programs. Finally,
      students who chose to study at a RCS are more likely to be female, of graduate
      entry, and of rural origin. CONCLUSIONS: Although little can be done regarding
      family and financial issues, these remain important concerns for students when
      considering relocation to a RCS. In addition, academic results and quality of
      teaching remain important concerns for students, despite evidence that, for the
      RCS, these are equal to or better than at The University of Melbourne
      metropolitan clinical schools.

PMID- 17532727
TI  - Synoviocyte infection with adeno-associated virus (AAV) is neutralized by human
      synovial fluid from arthritis patients and depends on AAV serotype.
AB  - Intraarticular gene transfer with adeno-associated viral (AAV) vectors may allow
      efficient therapeutic transgene expression within the joint in diseases such as
      rheumatoid arthritis (RA), allowing high expression of the protein within the
      joint, preventing both systemic diffusion and side effects. However, humans
      demonstrate antibodies against AAV, which can influence gene transfer. To better
      understand critical obstacles to intraarticular gene therapy with AAV, we have
      previously shown that synovial fluid (SF) contains IgG to AAV that neutralizes
      chondrocyte infection in vitro. Our objective was therefore to compare
      neutralization exerted by SF from RA patients for four different AAV serotypes
      (AAV serotypes 1, 2, 5, and 8) on human primary synoviocytes. Serotype 2 infected
      synoviocytes most efficiently followed, in decreasing order, by serotypes 1, 5,
      and 8. SF from all patients partially inhibited infection of synoviocytes by at
      least one of the four serotypes. Infection with serotypes 1 and 2 was the most
      inhibited by SF, whereas inhibition was weak for serotypes 5 and 8. Last, we have
      shown that inhibition of AAV1/interleukin (IL)-4 infection of synoviocytes by SF
      could be reversed by increasing the number of AAV1/IL-4 particles, with a dose
      dependent effect. We conclude that the most infectious AAV serotypes (1 and 2) in
      synoviocytes are also the serotypes most neutralized by SF. Thus, serotype 5
      seems to demonstrate the best infection efficiency:immunogenicity ratio for local
      use in articular diseases. These data may be useful for tailoring intraarticular
      AAV-mediated gene therapy to individual patients.

PMID- 17532728
TI  - To forgive is human, to err divine.

PMID- 17532729
TI  - Early phase methodology is needed in CAM and conventional research endeavors.

PMID- 17532730
TI  - Early phase research and the process of scientific discovery.

PMID- 17532731
TI  - HLA polymorphisms and genetic markers for traditional Chinese medicine.

PMID- 17532732
TI  - Investigation of cytokine expression in human leukocyte cultures with two immune
      modulatory homeopathic preparations.
AB  - BACKGROUND: The efficacy of homeopathic medicines for maintaining human health
      and treating disease has been extensively examined in clinical trials. However,
      there is a paucity of preclinical evaluations of the effects of homeopathic
      medicinal preparations on cellular signaling pathways relevant to the
      applications of these preparations. MATERIALS AND METHODS: In this study, the
      immune-modulatory effects of Phase 6 (for the stimulation of the nonspecific
      defense system) and Flu Terminator (for influenza and viral diseases) (Be Well
      Homeopathics Inc. Miami, FL), two homeopathic preparations developed for the
      purpose, were evaluated in normal human leukocyte cultures in vitro. RESULTS:
      Both Phase 6 and Flu Terminator stimulated the production of pro-and anti
      inflammatory cytokines by human leukocytes, although higher doses often produced
      a weaker response than lower doses. The carrier solvent (20% ethanol) failed to
      elicit any cytokine synthesis. CONCLUSIONS: The results of the in vitro studies
      suggested that ultralow concentrations of ingredients in Phase 6 and Flu
      Terminator were capable of eliciting a human immune response.

PMID- 17532733
TI  - Electrical skin impedance at acupuncture points.
AB  - OBJECTIVES: To test whether electrical skin impedance at each of three
      acupuncture points (APs) is significantly lower than at nearby sites on the
      meridian (MP) and off the meridian (NP). DESIGN: Two instruments - Prognos
      (MedPrevent GmbH, Waldershof, Germany), a constant-current (DC) device, and PT
      Probe (designed for this study), a 100-Hz sinusoidal-current (AC) device-were
      used to record electrical impedance at three APs (right Gallbladder 14, right
      Pericardium 8, and left Triple Energizer 1), and two control sites for each AP.
      Each AP, MP, and NP was measured four times in random order with each device.
      SETTING: The study was conducted over a period of 4 days at the Oregon College of
      Oriental Medicine (OCOM). SUBJECTS: Twenty (20) healthy adults (14 women and 6
      men), all recruited from the OCOM student body and faculty, participated in the
      study. RESULTS: The Prognos measurements had an intraclass correlation (ICC) =
      0.84 and coefficient of variation (CV) = 0.43. The PT Probe had ICC = 0.81 and CV
      = 0.31. Impedance values at APs were not significantly less than at MPs or NPs.
      Impedance values at MPs were also not significantly less than NPs, although their
      individual p values were <0.05 in 4 of 6 cases. There was a significant trend of
      increasing impedance with repeated measurements with both the Prognos (p =0.003)
      and the PT Probe (p= 0.003). CONCLUSIONS: Within the reliability limits of our
      study methods, none of the three APs tested has lower skin impedance than at
      either of the nearby control points. These results are not consistent with
      previous studies that detected lower skin impedance at APs than nearby sites.
      Further study is necessary to determine whether MPs have lower skin impedance
      than nearby NPs. Our study suggests caution is warranted when developing, using,
      and interpreting results from electrodermal screening devices. Further studies
      are needed to clarify the clinically important and controversial hypothesis that
      APs are sites of lower impedance.

PMID- 17532734
TI  - Yoga Asana sessions increase brain GABA levels: a pilot study.
AB  - OBJECTIVES: The aim of this study was to compare changes in brain gamma
      aminobutyric (GABA) levels associated with an acute yoga session versus a reading
      session. It was hypothesized that an individual yoga session would be associated
      with an increase in brain GABA levels. DESIGN: This is a parallel-groups design.
      SETTINGS/LOCATION: Screenings, scan acquisitions, and interventions took place at
      medical school-affiliated centers. SUBJECTS: The sample comprised 8 yoga
      practitioners and 11 comparison subjects. INTERVENTIONS: Yoga practitioners
      completed a 60-minute yoga session and comparison subjects completed a 60-minute
      reading session. OUTCOME MEASURES: GABA-to-creatine ratios were measured in a 2
      cm axial slab using magnetic resonance spectroscopic imaging immediately prior to
      and immediately after interventions. RESULTS: There was a 27% increase in GABA
      levels in the yoga practitioner group after the yoga session (0.20 mmol/kg) but
      no change in the comparison subject group after the reading session ( -0.001
      mmol/kg) (t = -2.99, df = 7.87, p = 0.018). CONCLUSIONS: These findings
      demonstrate that in experienced yoga practitioners, brain GABA levels increase
      after a session of yoga. This suggests that the practice of yoga should be
      explored as a treatment for disorders with low GABA levels such as depression and
      anxiety disorders. Future studies should compare yoga to other forms of exercise
      to help determine whether yoga or exercise alone can alter GABA levels.

PMID- 17532735
TI  - A qualitative review of the role of qigong in the management of diabetes.
AB  - OBJECTIVE: To review the evidence relating to the effectiveness of qigong in the
      management of diabetes. METHODS: We performed a systematic literature review of
      qigong intervention studies published in English or Chinese since 1980, retrieved
      from English-language databases and Chinese journals. Qigong intervention studies
      conducted with adults with diabetes, which reported both preintervention and
      postintervention measures of fasting blood glucose and/or hemoglobin
      A(1c)(HbA(1c)) were included. Sample characteristics, intervention
      frequency/duration, and metabolic outcomes were reviewed. RESULTS: Sixty-nine
      intervention studies were located. Of these, only 11 met the criteria for
      inclusion. There were consistent and statistically significant positive
      associations between participation in qigong and fasting and 2-hour oral glucose
      tolerance test results, blood glucose, and triglycerides and total cholesterol.
      Effects on insulin and HbA(1c) were inconsistent. There was no evidence of any
      effect of qigong on weight. Most of the studies were of short duration, involved
      small samples, and did not include a control group. CONCLUSIONS: Although qigong
      has beneficial effects on some of the metabolic risk factors for type 2 diabetes,
      methodologic limitations make it difficult to draw firm conclusions about the
      benefits reported. Randomized controlled trials are required to confirm the
      potential beneficial effects of qigong on the management of type 2 diabetes.

PMID- 17532736
TI  - Activity of a Lactobacillus acidophilus-based douche for the treatment of
      bacterial vaginosis.
AB  - OBJECTIVES: Bacterial vaginosis is characterized by alteration of the normal
      vaginal microflora, in which a mixed anaerobic bacterial flora becomes prevalent
      over the population of lacobacilli. Because administration of probiotics might be
      of some utility in restoring a normal flora, the present study aimed to evaluate
      the effect of a Lactobacillus acidophilus-strain-based douche on the vaginal
      environment in bacterial vaginosis. PATIENTS AND METHODS: In an open-label pilot
      evaluation, 40 women with bacterial vaginosis as defined by Amsel's criteria were
      treated for 6 days with a douche containing L. acidophilus. Vaginal smears were
      collected from the patients and analyzed according to Nugent's criteria at the
      time of diagnosis, after 6 days of treatment, and again at 20 days after the last
      treatment. At the same times, determination of vaginal pH and a Whiff test were
      performed. RESULTS: The Nugent score decreased significantly from bacterial
      vaginosis or an intermediate flora toward a normal flora during treatment, and
      remained low during the follow-up period for almost all of the patients,
      indicating bacterial vaginosis in 52.5% and in 7.5% of the patients before
      treatment and at follow-up, respectively. After treatment, significant decreases
      in vaginal pH were observed, to less than pH 4.5 in 34/40 women, and the odor
      test became negative in all of the patients. CONCLUSIONS: In this preliminary
      study, treatment of bacterial vaginosis with a vaginal douche containing a strain
      of L. acidophilus contributed to the restoration of a normal vaginal environment.

PMID- 17532737
TI  - Bactericidal activity of different types of honey against clinical and
      environmental isolates of Pseudomonas aeruginosa.
AB  - OBJECTIVES: Honey has had a valued place in traditional medicine for centuries.
      Renewed interest in honey for various therapeutic purposes, including treatment
      of infected wounds, has led to the search for different types of honey with
      antibacterial activity. In this study, we have assessed the antibacterial
      activity of different types of honey (manuka honey from Australia, heather honey
      from the United Kingdom, and locally marketed Indian honey). METHODS: The agar
      dilution method was used to assess the antibacterial activity of honey against
      152 isolates of Pseudomonas aeruginosa by determining minimum inhibitory
      concentrations. RESULTS AND CONCLUSIONS: The locally available (khadikraft) honey
      produced the best activity against Pseudomonas aeruginosa and was found to be
      better than all of the imported varieties of therapeutic honey.

PMID- 17532738
TI  - Successful treatment of metastatic malignant melanoma with Viscum album extract
      (Iscador M).
AB  - BACKGROUND: Recent study results demonstrate possible clinical benefit from
      adjuvant treatment with a standardized mistletoe (Viscum album) extract in
      patients with malignant melanoma. PATIENT AND METHOD: We present a male patient,
      currently 68 years of age, with one malignant melanoma at the upper part of the
      right arm since 1992, and another nodular melanoma at the left shoulder, first
      diagnosed in 1999. After discovery of the second melanoma and surgical resection,
      the patient was exclusively treated with standardized mistletoe extract (Iscador,
      (R)M; Weleda AG, CH-Arlesheim, Switzerland). COURSE OF THERAPY AND RESULTS: In
      June 1992, histologic analysis confirmed the presence of stage IA superficially
      spreading malignant melanoma with low infiltration of the papillary dermis in a
      skin excision sample from the upper part of the right arm. In November 1999,
      another melanoma was surgically removed at the patient's right shoulder. In this
      case, the histologic examination revealed nodular melanoma, stage IIA (pT3, pN0,
      M0). Therapy with mistletoe extract was introduced shortly afterwards as the sole
      adjuvant treatment. During the course of the mistletoe therapy, axillary removal
      of 8 lymph nodes became necessary, 3 of which proved to be metastatic. First
      signs of a defined solitary liver metastasis in an area next to segments IV and V
      were detected during an abdominal ultrasound examination in September 2001. This
      finding was confirmed by further sonographic examinations. The solitary liver
      metastasis was not resected, nor was classical antitumor treatment (chemotherapy
      or radiotherapy) initiated. The patient continued subcutaneous treatment with
      Iscador M after dose adaptation to 2 mg twice weekly (0.2 mL of a 10-mg vial);
      the treatment is still ongoing to the present. By June 2002, complete remission
      of the liver metastasis was diagnosed by liver ultrasound examination. There has
      been no local relapse so far, and the patient has been in stable condition ever
      since. No further metastases were discovered so far (as of May 2006).
      CONCLUSIONS: The use of low-dose Iscador as the sole postoperative modality for
      the adjuvant treatment of metastatic melanoma was extremely effective and very
      well tolerated in this patient. It achieved complete response and absence of all
      complaints.

PMID- 17532739
TI  - The importance of early phase research.
AB  - Early phase research in complementary and alternative medicine (CAM) is
      especially important because of the large influence it has on the subsequent
      expenditure of money and effort in particular areas of CAM therapies. The culture
      of biomedical research has, however, blurred the distinction between early and
      late-phase research, and this has distorted the very distinct aims of these two
      activities. The purpose of this paper is to reaffirm the critical role of early
      phase CAM research and to encourage CAM researchers to value and conduct early
      phase studies for their proper purposes.

PMID- 17532740
TI  - Searching for CAM evidence: an evaluation of therapy-specific search strategies.
AB  - OBJECTIVES: The aim of this investigation was to explore the effectiveness of
      search strategies developed to identify trials of specific complementary
      therapies in a range of clinical conditions. DESIGN: All primary studies included
      in a series of systematic reviews were identified. An analysis of the original
      source of the study and search term(s) by means of which the study had originally
      been retrieved was carried out. Each study was then searched for in each of 6
      databases (AMED, Cochrane CENTRAL, MEDLINE/PubMed, EMBASE, CINAHL, PsycINFO). The
      proportion of studies located on each database was assessed and the indexing
      terms identified for each therapy were compared against the original search
      strategies. RESULTS: A total of 127 primary studies were identified from 35
      systematic reviews. The number of studies on each therapy varied, but Cochrane
      CENTRAL listed the highest proportion for all therapies. No database listed all
      studies, and at least one unique study was listed on all databases except
      MEDLINE, whereas several studies were not found on any of the databases. Index
      terms were effective in locating studies on acupuncture, individual herbs,
      hypnosis, massage, and yoga. For the remaining therapies, use of text word search
      terms was important and particularly so for homeopathy, meditation, and
      reflexology. Variation in terminology for most of the therapies was encountered.
      CONCLUSIONS: The small numbers of studies preclude firm recommendations, but
      several potential challenges in searching for complementary and alternative
      medicine (CAM) trials are highlighted. The findings suggest that a range of
      different sources is required for identifying relevant studies, particularly for
      certain therapies. The development of an optimum generic search strategy for each
      therapy is hampered by the variation in indexing of CAM studies. Possible optimum
      strategies are presented as a basis for discussion, and further testing of the
      effectiveness of these strategies is now a priority.

PMID- 17532741
TI  - Promoting lifestyle self-awareness among the medical team by the use of an
      integrated teaching approach: a primary care experience.
AB  - OBJECTIVES: Healthy lifestyle is recommended in clinical guidelines for the
      prevention and treatment of chronic diseases such as cardiovascular disease and
      diabetes. Research previously identified a gap between lifestyle recommendations
      and their implementation in clinical practice. In this paper, we describe a pilot
      educational program aimed to promote providers' awareness of their own
      lifestyles, and to explore whether increased personal awareness enhances
      providers' willingness to engage in lifestyle-change discussion with patients.
      METHODS: Two primary-care urban clinics in Northern Israel participated in the
      program, which consisted of a series of six biweekly educational sessions, each
      lasting 2-4 hours. Each session included both knowledge-based and experiential
      learning based on complementary medicine modalities. Surveys at the end of the
      program and a year later provided the program evaluation. RESULTS: Thirty-five
      personnel participated in the program. Thirteen (13) of the 20 participants (65%)
      reported an attitude change regarding eating habits after the program. At 1-year
      follow up, 24 of the 27 respondents (89%) stated that they were more aware of
      their eating habits and of their physical activity compared with precourse
      status. Twenty-three (23) of 27 respondents (85%) stated that after the program
      they were better prepared to initiate a conversation with their patients about
      lifestyle change. CONCLUSIONS: An integrated educational approach based on
      knowledge-based and complementary and alternative medicine experiential
      modalities, aimed to facilitate self-awareness, may enhance learners' attitude
      change. The findings demonstrate readiness of learners to reexamine their
      lifestyles. Increased self-awareness helped participants to make a positive
      attitude change regarding eating habits and physical activity and was associated
      with participants' increased engagement in lifestyle-change discussions with
      patients. The teaching approach had longstanding effect, noted in the one-year
      follow-up.

PMID- 17532742
TI  - Policy for therapeutic massage in an academic health center: a model for standard
      policy development.
AB  - CONTEXT: Massage is the most common complementary and alternative medicine (CAM)
      therapy used in hospitals in the United States. As such, it is often the first
      CAM therapy to be integrated with conventional medicine. However, few academic
      medical centers have a written standard policy to guide this integration. This
      lack of standard policy may impede institutions from offering massage therapy as
      a clinical service, and may put health care professionals and institutions at
      risk through a failure to clearly address criteria for practice credentials or
      malpractice liability. OBJECTIVE: To create a clinical policy for therapeutic
      massage that may be used as a template for development of policy in academic
      health centers. RESULTS: We present a clinical policy for therapeutic massage,
      developed by the University of Michigan Health System, that defines therapeutic
      massage, provides guidelines for the credentialing and professional conduct of
      massage therapists, lists indications and contraindications for therapeutic
      massage, and addresses malpractice in accordance with the specific culture and
      needs of academic health centers. This policy was created by health care
      professionals after review of existing evidence and consideration of national
      criteria for massage therapy. This policy is intended to be used as a template
      for the development of a standard policy for therapeutic massage by health system
      administrators, medical directors, and massage professionals, to support the
      integration of therapeutic massage within their institutions. CONCLUSIONS: With
      minor modifications of this policy by individual institutions, adoption of this
      policy may facilitate the thoughtful integration of this CAM therapy into
      academic health care settings, meeting the unique requirements of academic health
      care institutions while serving the needs of patients.

PMID- 17532743
TI  - News from the International Society for Complementary Medicine Research.

PMID- 17532744
TI  - Short-term retention of labeled chondrocyte subpopulations in stratified tissue
      engineered cartilaginous constructs implanted in vivo in mini-pigs.
AB  - It is likely that effective application of cell-laden implants for cartilage
      defects depends on retention of implanted cells and interaction between implanted
      and host cells. The objectives of this study were to characterize stratified
      cartilaginous constructs seeded sequentially with superficial (S) and middle (M)
      chondrocyte subpopulations labeled with fluorescent cell tracking dye PKH26 (*)
      and determine the degree to which these stratified cartilaginous constructs
      maintain their architecture in vivo after implantation in mini-pigs for 1 week.
      Alginate-recovered cells were seeded sequentially to form stratified S*/M (only S
      cells labeled) and S*/M* (both S and M cells labeled) constructs. Full-thickness
      defects (4 mm diameter) were created in the patellofemoral groove of adult
      Yucatan mini-pigs and filled with portions of constructs or left empty.
      Constructs were characterized biochemically, histologically, and biomechanically,
      and stratification visualized and quantified, before and after implant. After 1
      week, animals were sacrificed and implants retrieved. After 1 week in vivo,
      glycosaminoglycan and collagen content of constructs remained similar to that at
      implant, whereas DNA content increased. Histological analyses revealed features
      of an early repair response, with defects filled with tissues containing little
      matrix and abundant cells. Some implanted (PKH26-labeled) cells persisted in the
      defects, although constructs did not maintain a stratified organization. Of the
      labeled cells, 126 +/- 38% and 32 +/- 8% in S*/M and S*/M* constructs,
      respectively, were recovered. Distribution of labeled cells indicated
      interactions between implanted and host cells. Longer-term in vivo studies will
      be useful in determining whether implanted cells are sufficient to have a
      positive effect in repair.

PMID- 17532745
TI  - Migration rates and genetic structure of two Hungarian ethnic groups in
      Transylvania, Romania.
AB  - Transylvania's ethnic mosaic is composed of Romanians, German Saxons and
      Hungarians. The ethnic groups of the Hungarian minority that settled in Romania
      show differences in dialects, customs and religious affiliations. In this study
      entire mtDNA control region sequences from 360 individuals of Hungarian ethnicity
      from two populations (the Csango and the Szekely), settled in the historical
      region of Transylvania in Romania, were generated and analyzed following high
      quality sequencing standards. Phylogenetic analyses were used for haplogroup
      determination, quasi-median network analyses were applied for the visualization
      of character conflicts, and median joining reconstructions were used for
      depicting haplotype structures. Affiliation of haplotypes to major west Eurasian
      haplogroups was confirmed using coding region SNPs. Gene flow between the two
      populations was low and biased towards a higher migration rate from the Csango to
      the Szekely than vice versa. Phylogeographic analyses revealed effects of genetic
      isolation within the Csango population, which is, in its genetic structure,
      clearly different from the Szekely population. The pronounced genetic divergence
      between the two populations is in sharp contrast to the expectation of high
      genetic similarity due to the close geographic proximity of their native
      homelands. The population data will be incorporated in the EMPOP database
      (http://www.empop.org).

PMID- 17532747
TI  - Treatment of HCC in patients awaiting liver transplantation.
AB  - Liver transplantation (LT) is the treatment of choice for many patients with
      unresectable hepatocellular carcinoma (HCC), but long waiting time due to the
      shortage of donor organs can result in tumor progression and drop-out from LT
      candidacy. Furthermore, even in candidates meeting the restrictive Milan criteria
      there is risk of HCC recurrence; this risk rises significantly when patients with
      more advanced HCC are included. In an effort to address these issues, treatment
      of HCC in patients awaiting LT has become widespread practice. In this review the
      various modalities employed in the pre-LT setting are presented, and the evidence
      for benefit with regard to (1) improvement of post-LT survival, (2) down-staging
      of advanced HCC to within Milan criteria and (3) preventing waiting list drop-out
      is considered. Chemoembolization, radiofrequency ablation and ethanol injection
      all have well-documented antitumor activity; however, there is no high level
      evidence that waiting list HCC treatment with these modalities is effective in
      achieving any of the three above-mentioned aims. Nevertheless, particularly in
      the United States, where continued waiting list priority depends on maintaining
      HCC within Milan criteria, use of nonsurgical HCC treatment will likely continue
      in an effort to forestall tumor progression and waiting list drop-out.

PMID- 17532749
TI  - A semi-centennial report on the participants depicted in Joel Babb's portrait,
      'the first successful kidney transplantation'.
AB  - Joseph Murray performed the first successful human kidney transplant on December
      23, 1954. Forty-three years later, he along with participants Francis Moore and
      Leroy Vandam, commissioned a painting of the event from artist Joel Babb (1). To
      document this unique record of medical history, we identify all those present at
      the operation and depicted in the portrait, describe how the artist created the
      work, explain irregularities and inaccuracies in the painting, provide a 50-year
      follow-up on everyone involved, and comment on any influence this landmark event
      may have had on their subsequent careers.

PMID- 17532750
TI  - Plasma concentrations of mycophenolic acid acyl glucuronide are not associated
      with diarrhea in renal transplant recipients.
AB  - The aim of this study was to determine whether plasma concentrations of the acyl
      (AcMPAG) and phenolic (MPAG) glucuronide metabolites of mycophenolic acid (MPA)
      were related to diarrhoea in renal transplant patients on mycophenolate mofetil
      (MMF) with cyclosporine (CsA) or tacrolimus (TCL). Blood samples (0, 30, 120 min)
      were taken at days 3, 10, week 4, months 3, 6 and 12 for determination of MPA,
      MPAG and AcMPAG. MPA-AUC was estimated using validated algorithms. Two hour AUCs
      were calculated for MPAG and AcMPAG. Immunosuppressive therapy consisted of
      CsA/MMF (n= 110) and of TCL/MMF (n= 180). In 70/290 (24%) patients 86 episodes of
      diarrhoea were recorded during 12 months. Significantly more patients on TCL
      (31.1%) suffered from diarrhea compared to CsA (12.7%). MMF dose, MPA-AUC and the
      2 h AUCs of MPAG and AcMPAG did not differ between patients with and without
      diarrhoea. Plasma AcMPAG and MPAG concentrations were substantially higher in
      patients on CsA compared with TCL, while MPA-AUC was lower in the former group.
      These data support the concept that CsA inhibits the biliary excretion of MPAG
      and AcMPAG, thereby potentially reducing the risk of intestinal injury through
      enterohepatic recycling of MPA and its metabolites.

PMID- 17532751
TI  - Effect of inhaled tacrolimus on cellular and humoral rejection to prevent
      posttransplant obliterative airway disease.
AB  - This study aimed to investigate the pharmacokinetics after tacrolimus aerosol
      inhalation and to assess its efficacy to suppress acute and chronic airway
      allograft rejection. Orthotopic tracheal transplantations were performed and
      tacrolimus (4 mg/kg) was administered orally (PO) or via aerosol (AER). Tracheal
      tissue level AUCs(0-12) were similar in both treatment groups, but blood AUCs(0
      12) were approximately 5.5-fold lower with AER (p < 0.001). Interestingly, only
      PO animals showed elevated BUN, cholesterol and triglycerides on POD 60 (p <
      0.05). Histology of grafts harvested after 6 and 60 days revealed that both
      treatment groups were similarly effective in suppressing graft mononuclear
      infiltration (p < 0.001). Cellular immune activation (assessed by IFN-gamma- and
      IL-4-ELISPOTS), however, was far more effectively suppressed by tacrolimus PO (p
      < 0.001). In both treatment groups, the vigorous alloreactive IgM-antibody surge
      was effectively inhibited (p < 0.001). Due to the insufficient systemic cellular
      immunosuppression, discontinuation of tacrolimus AER resulted in a far stronger
      (3.5-fold) graft infiltration on POD 8 compared to PO (p < 0.001). Tacrolimus
      aerosol reduces systemic side effects and effectively protects the airway graft
      from early cellular rejection and chronic obliterative airway disease.

PMID- 17532752
TI  - Simultaneous liver-kidney transplantation: evaluation to decision making.
AB  - Questions about appropriate allocation of simultaneous liver and kidney
      transplants (SLK) are being asked because kidney dysfunction in the context of
      liver failure enhances access to deceased donor organs. There is specific concern
      that some patients who undergo combined liver and kidney transplantation may have
      reversible renal failure. There is also concern that liver transplants are placed
      prematurely in those with end-stage renal disease. Thus to assure allocation of
      transplants only to those truly in need, the transplant community met in March
      2006 to review post-MELD (model for end-stage liver disease) data on the impact
      of renal function on liver waitlist and transplant outcomes and the results of
      SLK.

PMID- 17532753
TI  - Sticky platelet syndrome: an underrecognized cause of graft dysfunction and
      thromboembolic complications in renal transplant recipients.
AB  - Sticky platelet syndrome (SPS) leads to hyperaggregabilty of platelets in
      response to physiologic stimuli. In this report we describe three patients with
      clinical symptoms of SPS after renal transplantation. The first patient developed
      an infarction of her transplant kidney with additional, subsequent renal
      microinfarctions. The second patient suffered multiple strokes and deep vein
      thrombosis with episodes of pulmonary embolism and ischemic bowel disease due to
      colonic microinfarctions. The third patient experienced a long episode of
      unexplained respiratory and graft dysfunction immediately after transplantation
      until therapy for SPS was initiated, at which point symptoms resolved quickly.
      Kidney transplant recipients with SPS may be at increased risk of developing
      thrombosis, given that most immunosuppressive drugs are known to induce either
      endothelial cell damage or augment platelet aggregation. All patients awaiting
      renal transplantation should be screened for a history of thrombosis and, if
      appropriate, tested for SPS. Affected patients should receive dose-adjusted
      acetylsalicylic acid.

PMID- 17532754
TI  - Reperfusion of the liver allograft with blue blood: is it still the royal
      perfusate?
AB  - The technique of liver transplantation has become relatively standardized.
      Although not commonly practiced, arterial reperfusion has been shown in both
      animal and human trials to offer hemodynamic and functional benefits to liver
      allograft recipients. Whether this is the result of shortening the time to re
      establishing arterial perfusion or an effect of the sequence which the liver is
      revascularized remains unknown. Further randomized clinical trials are needed to
      answer this question and support our practice of arterial reperfusion.

PMID- 17532755
TI  - Diagnostic biomarker of asbestos-related mesothelioma: example of translational
      research.
AB  - Mesothelioma is an aggressive tumor arising from the mesothelium, and is usually
      associated with previous exposure to asbestos. The incubation period of asbestos
      related mesothelioma is estimated to be approximately 30-40 years. Once
      mesothelioma has occurred, there is no effective treatment. So, identification of
      tumor markers and a method for early diagnosis using such markers are urgently
      needed. Recently, several enzyme-linked immunosorbent assay systems for
      Erc/mesothelin have been developed, the reported usefulness of which has been
      assessed and demonstrated as a diagnostic tool. Asbestos-related mesothelioma
      should be ascribed as a typical environmental carcinogen. In this review, we will
      present asbestos-related mesothelioma for the study of problems in environmental
      carcinogenesis.

PMID- 17532756
TI  - Organ-dependent susceptibility of p53 knockout mice to 2-amino-3
      methylimidazo[4,5-f]quinoline (IQ).
AB  - p53 knockout mice are now being frequently used to identify the carcinogenic
      potential of chemicals, thus it is important to precisely assess the
      susceptibility of the animals to various test chemicals. In the present study the
      susceptibility of p53 nullizygous((-/-)), heterozygous((+/-)), and wild
      type((+/+)) mice to 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) was
      investigated. Mice of all three genotypes were first fed a diet containing 100 or
      300 p.p.m. IQ for 15 weeks in a short-term experiment. p53((+/-)) and ((+/+))
      mice were then treated with IQ for 40 weeks and maintained without further
      treatment for an additional 12 weeks in the long-term experiment. In the
      forestomach, the incidence of squamous cell hyperplasia was significantly higher
      in p53((-/-)) than in ((+/-)) and ((+/+)) mice at 15 weeks and higher in ((+/-))
      mice than ((+/+)) mice with long-term IQ treatment, indicating an elevated
      susceptibility of p53 knockout mice. In contrast, in the liver, various
      hepatocellular lesions developed mainly in female mice with long-term IQ exposure
      but no significant differences were evident between p53 knockout and wild-type
      mice, indicating a lack of elevated susceptibility in the knockout animals.
      Furthermore, polymerase chain reaction-single strand conformation polymorphism
      and sequencing analysis revealed relatively high (13/30) and low (1/15)
      incidences of p53 mutations (exons 5-8) in squamous cell hyperplasia and
      hepatocellular tumors, respectively. These results clearly indicate that the
      susceptibility of p53 knockout mice is organ-dependent, coinciding to some extent
      with the likelihood of p53 gene alteration in the induced tumors.

PMID- 17532757
TI  - Increased expression of h-prune is associated with tumor progression and poor
      survival in gastric cancer.
AB  - The human homolog of the Drosophila prune protein (from PRUNE, which encodes h
      prune), which interacts with glycogen synthase kinase 3, promotes cellular
      motility. H-prune also interacts with nm23-H1, a suppressor of cancer metastasis.
      It has been reported that stimulation of cellular motility by h-prune is enhanced
      by its interaction with nm23-H1 in breast cancer cells. In the present study, we
      examined the expression of h-prune and nm23-H1 during tumor progression in
      gastric cancer (GC). PRUNE mRNA was overexpressed in 12 (32%) of 38 GC cases by
      quantitative reverse transcription-polymerase chain reaction. PRUNE mRNA levels
      correlated significantly with advanced T grade, N grade and tumor stage.
      Immunohistochemical analysis revealed that 43 (30%) of 143 GC cases were positive
      for h-prune, and h-prune-positive GC cases showed more advanced T grade, N grade
      and tumor stage than h-prune-negative GC cases. One hundred and twenty-four (87%)
      of 143 GC cases were positive for nm23-H1, and nm23-H1 was expressed in almost
      all (42 cases, 98%) h-prune-positive GC cases. Many GC cases positive for both h
      prune and nm23-H1 showed more advanced T grade, N grade and tumor stage than
      other type GC cases. Patients with h-prune-positive GC had a significantly worse
      survival rate than patients with h-prune-negative GC. These findings indicate
      that overexpression of h-prune is associated with tumor progression and
      aggressiveness of GC. nm23-H1 may enhance motility of cancer cells by interacting
      with h-prune.

PMID- 17532758
TI  - Congenital hypothyroidism with goitre caused by new mutations in the
      thyroglobulin gene.
AB  - CONTEXT: Thyroid dyshormonogenesis is associated with mutations in the
      thyroglobulin (TG) gene and characterized by normal organification of iodide and
      low serum TG. These mutations give rise to congenital goitrous hypothyroidism,
      transmitted in an autosomal recessive mode. OBJECTIVES: The aim of this study was
      to identify new mutations in the TG gene in an attempt to increase the
      understanding of the molecular basis of this disorder. Three unrelated patients
      with marked impairment of TG synthesis were studied. METHODS: The promoter and
      the complete coding regions of the TG gene, along with the flanking intronic
      regions, were analysed by direct DNA sequencing. RESULTS: Four different
      inactivating TG mutations, three novel mutations (c.548G>A, p.C164Y; c.759
      760insA, p.L234fsX237; c.6701C>A, p.A2215D) and one previously identified
      mutation (c.886C>T, p.R277X) were identified. Multiple sequence alignment study
      revealed that the wild-type cysteine residue at position 164 is strictly
      conserved in the TG of all the species analysed, whereas the wild-type alanine
      residue at position 2215 is well conserved in the TG and acetylcholinesterase
      (AChE) of all the species analysed except in rabbit AChE, in which it is
      substituted by glutamic acid. CONCLUSIONS: We report three patients with
      congenital hypothyroidism with goitre caused by two compound heterozygous
      mutations, p.C164Y/p.L234fsX237 and p.R277X/p.A2215D, and one homozygous
      mutation, p.R277X, in the TG gene. To our knowledge this is the first report of
      the presence of a nucleotide insertion mutation in the TG gene.

PMID- 17532759
TI  - Glucocorticoid receptor gene polymorphisms and susceptibility to rheumatoid
      arthritis.
AB  - BACKGROUND: A defect in hypothalamic-pituitary-adrenal (HPA) axis function has
      been suggested to contribute to susceptibility to rheumatoid arthritis (RA).
      OBJECTIVE: To investigate polymorphisms of the glucocorticoid receptor (GR) gene
      and determine any associations with RA. METHODS: Three GR polymorphisms that tag
      95% of all haplotypes across the GR gene were genotyped. These are an intron B
      Bcl1 polymorphism, a ttg insertion/deletion within intron F (rs2307674) and the
      single nucleotide polymorphism (SNP) lying in the 3' untranslated region of exon
      9b (rs6198). The dye terminator-based SNaPshot method or size resolution by
      capillary electrophoresis was performed. The study population comprised 198 UK
      Caucasian RA cases and 393 ethnically matched controls. RESULTS: No significant
      single point or haplotypic associations were found for GR polymorphisms with RA
      susceptibility. Furthermore, no evidence for GR polymorphisms with aspects of RA
      severity was seen. CONCLUSION: In this study of the most comprehensive coverage
      of GR polymorphisms with RA, no significant contributing role for GR
      polymorphisms with RA was found.

PMID- 17532760
TI  - Human GCIP interacts with CT847, a novel Chlamydia trachomatis type III secretion
      substrate, and is degraded in a tissue-culture infection model.
AB  - The obligate intracellular bacterium Chlamydia trachomatis occupies a
      parasitophorous vacuole and employs a type III secretion mechanism to translocate
      host-interactive proteins. These proteins most likely contribute to pathogenesis
      through modulation of host cell mechanisms crucial for the establishment and
      maintenance of a permissive intracellular environment. Using a surrogate Yersinia
      type III secretion system (T3SS), we have identified the conserved gene product
      CT847 as a chlamydial T3SS substrate. Yeast two-hybrid studies using CT847 as
      bait to screen a HeLa cell cDNA library identified an interaction with mammalian
      Grap2 cyclin D-interacting protein (GCIP). Immunoblot analyses of C. trachomatis
      infected HeLa cells showed that GCIP levels begin to decrease (as compared with
      mock-infected HeLa cells) between 8 h and 12 h post infection. GCIP was virtually
      undetectable in 24 h time point material. This decrease was inhibited by
      proteasome inhibitors lactacystin and MG-132, and the T3SS inhibitor Compound 1.
      CT847 was detectible in purified reticulate body but not elementary body lysates,
      and reverse transcription polymerase chain reaction (RT-PCR) expression analyses
      indicate a mid-cycle expression pattern. Both of these findings are consistent
      with CT847 contributing to the observed effect on GCIP. Given the established
      roles of GCIP, we believe that we have discovered a novel C. trachomatis antihost
      protein whose activity is relevant to chlamydial pathogenesis.

PMID- 17532761
TI  - Immunophenotypic analysis of Epstein-Barr virus (EBV)-infected CD8(+) T cells in
      a patient with EBV-associated hemophagocytic lymphohistiocytosis.
AB  - Hemophagocytic lymphohistiocytosis (HLH) is a severe and often fatal condition
      characterized by uncontrolled activation of T cells and macrophages. In Epstein
      Barr virus (EBV)-associated HLH (EBV-HLH), the pathogenic roles of ectopic EBV
      infection in the T-cell population and of clonal proliferation of EBV-infected T
      cells has been described. However, the immunophenotype of EBV-infected T cells
      has not been fully characterized. Here we describe a case of EBV-HLH presenting
      with a massive clonal proliferation of CD8(+) T cells with TCR VB14. Analysis of
      in situ hybridization for EBV-encoded small RNA1 showed that only CD8(+) T cells
      harbored EBV in this patient. The EBV-infected TCR VB14(+) CD8(+) T cells
      exhibited unique immunophenotypic features including lacked CD5 expression and a
      markedly bright expression of HLA-DR. After initiation of treatment with
      prednisolone, etoposide, and cyclosporin A, the percentage of infected cells
      declined progressively in parallel with other serum markers such as ferritin.
      These findings suggest that lacking expression of CD5 on CD8(+) T cells with
      specific TCR VB may serve as a useful marker of dysregulated T-cell activation
      and proliferation in EBV-HLH.

PMID- 17532762
TI  - False-positive FDG-PET findings due to bone metastasis from prostate cancer in
      staging of non-Hodgkin's lymphoma.

PMID- 17532763
TI  - Absence of CASP7 and CASP8 mutation in gastrointestinal lymphomas.

PMID- 17532764
TI  - The soluble transferrin receptor in dysplastic erythropoiesis in myelodysplastic
      syndrome.
AB  - OBJECTIVES: In individuals without iron deficiency, the soluble transferrin
      receptor (sTfR) directly reflects the erythropoietic activity. This study
      investigated sTfR concentrations in ineffective, dysplastic erythropoiesis in
      myelodysplastic syndrome (MDS). METHODS: To exclude influences of other myeloid
      cells on sTfR, only patients with refractory anemia (RA), refractory anemia with
      ringed sideroblasts (RARS) and 5q(-) syndrome were included. sTfR was measured
      nephelometrically (normal range 0.81-1.75 mg/L). RESULTS: Thirty-four untreated
      MDS patients (RA = 14, RARS = 10, 5q(-) syndrome = 10) were enrolled and
      analysed. The mean sTfR value of all MDS patients (1.30 +/- 0.8 mg/L, range 0.2
      3.8) did not differ from our control group. In 5q(-) syndrome, the mean sTfR
      concentration (0.80 +/- 0.5 mg/L) was significantly lower than in RA (1.32 +/-
      0.4 mg/L, P = 0.02) and RARS (1.75 +/- 1.1 mg/L, P = 0.03). Subdividing MDS
      according to their amount of erythroid mass in bone marrow a significant
      difference of sTfR between patients with decreased (0.70 +/- 0.4 mg/L), normal
      (1.32 +/- 0.4 mg/L) and increased (2.06 +/- 0.9 mg/L) erythropoiesis was
      observed. MDS patients with sTfR values below the reference range of 0.81 mg/L
      required transfusions in 90% of cases and showed higher erythropoietin levels
      compared to MDS patients with sTfR levels > or =0.81 mg/L (P = 0.01). There was a
      good agreement between sTfR and the amount of polychromatic erythroblasts
      observed (r = 0.68, P < 0.001). CONCLUSION: In conclusion, the serum
      concentration of sTfR reflects erythropoietic activity in MDS, but it is in
      particular determined by the degree of erythroid maturation and the severity of
      ineffective erythropoiesis. Low sTfR values in MDS are associated with a reduced,
      poorly differentiated erythropoiesis and requirement of blood transfusions.

PMID- 17532765
TI  - The effect of ranitidine on antibody responses to polysaccharide vaccines in
      patients with B-cell chronic lymphocytic leukaemia.
AB  - OBJECTIVES: To analyse the effects of ranitidine treatment on vaccination induced
      antibody responses in patients with chronic lymphocytic leukaemia (CLL). METHODS:
      Fifty CLL patients were vaccinated with tetanus conjugated Hib vaccine and a 23
      valent pneumococcal polysaccharide vaccine with (n = 25) or without (n = 25)
      ranitidine treatment in a matched case--control setting. Anti tetanus toxoid
      (TT), anti-Hib and anti-pneumococcal antibody levels were determined before and
      after vaccination. Additionally, cytokine levels were assessed in patients
      treated with ranitidine. RESULTS: Vaccination-induced increases in anti-Hib and
      anti-TT antibody levels were higher in the ranitidine group compared with the
      control group. Anti-pneumococcal antibody responses were not improved by
      administration of ranitidine. Higher levels of IL-18 were found in patients
      treated with ranitidine compared with healthy controls. Levels of IL-6, IL-8, IL
      18, RANTES, IP-10, sVCAM-1 and sICAM-1 were within normal ranges and did not
      change during ranitidine treatment. CONCLUSION: Ranitidine treatment improves
      vaccination-induced T-cell dependent antibody responses in patients with CLL but
      has no beneficial effect on the response to vaccination with unconjugated
      polysaccharide antigens.

PMID- 17532766
TI  - Rituximab for warm-type idiopathic autoimmune hemolytic anemia: a retrospective
      study of 11 adult patients.
AB  - Warm-type idiopathic autoimmune hemolytic anemia (AIHA) is a relatively common
      hematologic disorder resulting from autoantibody production against red blood
      cells. Steroids represent the first-line therapeutic option, and
      immunosuppressive agents as well as splenectomy are used for refractory cases.
      Recently, the anti-CD20 monoclonal antibody rituximab has been shown to control
      autoimmune hemolysis in patients with refractory chronic disease. We report
      results from a retrospective analysis of 11 adult patients receiving rituximab
      for steroid-refractory AIHA of the warm type at a mean age of 55 yr (range 23-81
      yr). All patients were given methyl-prednisolone as first-line treatment and some
      of them also received azathioprine and intravenous high-dose immunoglobulins. One
      patient underwent splenectomy. All patients were considered refractory to
      steroids and/or immunosuppressive drugs and all were then given weekly rituximab
      (375 mg/m(2)) for four consecutive weeks. An increase in hemoglobin (Hgb) levels
      in response to rituximab, with a mean increment of 3.3 g/dL (95% CI 2.1-4.4), was
      observed in all cases. Four patients required packed red cell transfusions before
      starting rituximab and all became transfusion-free. At a mean follow-up of 604 d
      (range 30-2884 d) since the treatment of AIHA with rituximab, all patients are
      alive, eight (73%) of them in complete remission (CR) and three (27%) in partial
      remission (PR). A moderate hemolysis still persisted in six (54%) patients. In
      conclusion, our experience clearly demonstrates that anti-CD20 monoclonal
      antibody rituximab is an effective and safe alternative treatment option for
      idiopathic AIHA, in particular, for steroid-refractory disease.

PMID- 17532767
TI  - LRP16 is fused to RUNX1 in monocytic leukemia cell line with t(11;21)(q13;q22).
AB  - OBJECTIVE: The RUNX1 (also known as AML1) gene is observed frequently as the
      target of chromosomal rearrangements in human acute leukemia. We describe here a
      previously unreported rearrangement, t(11;21)(q13;q22), that disrupts the RUNX1
      gene in a patient with acute leukemia and the molecular analysis of the fusion
      gene. METHODS: We have established a monocytic leukemia cell line, ELAM-1, from a
      patient with acute leukemia evolving from myelodysplastic syndrome (MDS).
      Translocation (11;21) (q13;q22) was observed in both patient leukemia cells and
      ELAM-1. RESULTS: The split signal of RUNX1 was detected by fluorescence in situ
      hybridization and indicated the involvement of RUNX1 in ELAM-1. Using 3'- Rapid
      amplification of cDNA ends and reverse transcription-Polymerase chain reaction
      analysis, we detected both RUNX1 (exon 5)-LRP16 and RUNX1 (exon 6)-LRP16
      transcripts, suggesting that the RUNX1 breakpoint lies in intron 6 and that
      alternative fusion splice variants are generated. Reciprocal LRP16-RUNX1 fusion
      was also detected. CONCLUSIONS: We identified a novel RUNX1 fusion partner, LRP16
      on 11q13 involving t(11;21)(q13;q22). Although it was reported that
      overexpression of LRP16 promotes human breast cancer cell proliferation, the
      function of LRP16 in leukemia remains to be studied. This fusion gene and cell
      line may provide a new research tool to investigate the mechanism of
      leukemogenesis generated by the RUNX1 fusion gene.

PMID- 17532768
TI  - Colorectal tumour deposits in the mesorectum and pericolon; a critical review.
AB  - Although tumour deposits (TD) in the pericolic and mesorectal fat have been
      recognized since 1935, incorporation in the Tumour Node Metastasis (TNM)/American
      Joint Committee on Cancer (AJCC) system took place in 1997. The 3-mm rule
      classified TD as lymph node metastases. This rule was changed in 2002, when the
      contour of the deposit became the diagnostic feature. This review has evaluated
      the 3714 patients described in the literature. The incidence of TD varies from 5
      to 45%. Their origin has been shown to be heterogeneous; however, their presence
      indicates a poorer survival. The hazard ratio for death due to disease is 1.96.
      Various studies have tried to determine the importance of types of TD, based on
      contour, size and origin, but all fail to provide an evidence base to
      substantiate its use in the TNM system. To classify TD as positive lymph nodes
      after neoadjuvant therapy is a misconception, since the presence of tumour
      microfoci after therapy can be a sign of good response to treatment and
      indicative of a good prognosis. In conclusion, we did not find adequate evidence
      for the inclusion of TD in TNM/AJCC staging systems. Moreover, the current
      directives are confusing, and the definitions should not be used after
      neoadjuvant therapy.

PMID- 17532769
TI  - Increased neurokinin-2 receptor expression in alveolar macrophages of smokers
      with COPD.

PMID- 17532770
TI  - Two cases of hepatoid adenocarcinoma of the intestine in association with
      inflammatory bowel disease.

PMID- 17532771
TI  - Inexpensive and precise paraffin tissue microarrays constructed with a computer
      numerical control (CNC) drilling machine.

PMID- 17532772
TI  - Osteochondritis dissecans.

PMID- 17532773
TI  - Salivary duct carcinoma of the parotid gland presenting KIT (CD117)
      overexpression.

PMID- 17532774
TI  - Penetration depth of a dye marker into dentine using a novel hydrodynamic system
      (RinsEndo).
AB  - AIM: To investigate the efficiency of a hydrodynamic irrigation system compared
      with conventional cleansing techniques in root canals. METHODOLOGY: Forty-five
      freshly extracted single-rooted teeth were de-coronated and their root canals
      were enlarged to size 30 at the apex. The teeth were randomly divided into three
      groups (n = 15) for the final rinsing sequence using 2% NaOCl plus acid fuchsin:
      group I: static application of irrigant, 3 min; group II: flushing with a
      syringe; 5-mL NaOCl, 1 min; group III: RinsEndo-system; 5-mL NaOCl, 50 s. Apical
      extrusion was documented photographically. The roots were sectioned at 2, 4, 6
      and 8 mm from their apices and the penetration depths of dye into dentine
      measured, using a stereomicroscope. Wilcoxon's test and Pearson's chi-squared
      test were employed to prove statistic relevance. RESULTS: Greater dye penetration
      depth into the dentinal tubules was achieved when employing hydrodynamic rinsing
      procedures. Using this technique, 23% of the specimens were penetrated for more
      than 50% of their dentine thickness, whereas the results for flushing with a
      syringe were 12% (static application, 7%). No penetration of dentine occurred in
      63% of specimens with static application, 39% flushing with a syringe and 15%
      using the hydrodynamic system (P < 0.05 Pearson's chi-squared test). Apical
      extrusion occurred more frequently after hydrodynamic rinsing (extruded
      specimens: RinsEndo = 80%; static application/flushing with a syringe = 13%; P <
      0.05 Pearson's chi-squared test). CONCLUSIONS: Hydrodynamic rinsing demonstrated
      an improvement over conventional methods in terms of dentine penetration of a dye
      marker. A higher risk of apical extrusion with the RinsEndo-system was evident.

PMID- 17532775
TI  - Fatigue testing of a NiTi rotary instrument. Part 1: Strain-life relationship.
AB  - AIM: To examine the fatigue behaviour using a strain-life approach, and to
      determine the effect of water on the fatigue life of a NiTi rotary instrument.
      METHODOLOGY: Instruments of one brand of NiTi engine-file (size 25, ProFile 0.04
      and 0.06) were subjected to rotational bending either in air or under water, the
      number of revolutions to fracture (N(f)) being recorded using an optical counter
      and an electronic break-detection circuit. The effective surface strain amplitude
      (epsilon(a)) for each specimen was determined from the curvature of the
      instrument (on a photograph) and the diameter of the fracture cross-section (from
      a scanning electron micrograph of the fracture surface). Strain was plotted
      against fatigue life and the low-cycle fatigue (LCF) region identified. Values
      were examined using two-way analysis of variance for difference between various
      instrument-environment combinations. RESULTS: A total of 212 instruments were
      tested. A strain-life relationship typical of metals was found. N(f) declined
      with an inverse power function dependence on epsilon(a). A fatigue limit was
      present at about 0.7% strain. The apparent fatigue-ductility exponent, a material
      constant for the LCF life of metals, was found to be between -0.45 and -0.55.
      There was a significant effect of the environmental condition on the LCF life,
      water being more detrimental than air. CONCLUSIONS: The fatigue behaviour of NiTi
      rotary instrument is typical of most metals, provided that the analysis is based
      on the surface strain amplitude, and showed a high-cycle and a LCF region. The
      LCF life is adversely affected by water.

PMID- 17532776
TI  - Accidental ingestion and aspiration of root canal instruments and other dental
      foreign bodies in a French population.
AB  - AIM: To determine the incidence of aspiration and ingestion of endodontic
      instruments in France during root canal treatment without using rubber dam.
      METHODOLOGY: Data was provided by two insurance companies representing 24,651
      French general dentists over 11 years. The type and number of accidents per year,
      the number of dental items involved and the percentage of occurrence of either
      aspiration or ingestion were reported. The incidence of accidental aspiration or
      ingestion was calculated. The need for hospitalization to remove the endodontic
      instruments and other dental items was reported and compared using chi square
      tests. RESULTS: One endodontic instrument was aspirated and 57 were ingested.
      Forty-three other dental items were aspirated and 409 were ingested. For the
      endodontic instruments: the incidence of aspiration was 0.001 per 100,000 root
      canal treatments and the incidence of ingestion was 0.12 per 100,000 root canal
      treatments. The aspirated endodontic instruments and dental items required
      statistically more frequent hospitalization than the ingested items (P < 0.0001).
      The endodontic instruments did not require more frequent hospitalization than
      other dental items when aspirated (ns) and when ingested (ns). No fatal outcome
      was reported. CONCLUSION: The incidence of ingestion or aspiration of endodontic
      instruments was low even thought most general practitioners do not routinely use
      rubber dam. Use of rubber dam by general practitioners for endodontic procedures
      should be encouraged by stressing its advantages rather than the fear factor of
      accidents.

PMID- 17532777
TI  - Baseball, crackers, green dust, nose candy, and snow cones: cocaine,
      defibrillation, and ICDs.

PMID- 17532779
TI  - Elimination of the left atrial appendage during mitral valve surgery does not
      prevent stroke or embolism.

PMID- 17532780
TI  - Pacemaker inhibition: a manifestation of an unusual form of device-device
      interaction.

PMID- 17532781
TI  - Mitral isthmus conduction block after a single radiofrequency application for a
      left concealed accessory pathway.

PMID- 17532782
TI  - Heat shock protein gene 70-2 polymorphism is differentially associated with the
      clinical phenotypes of ulcerative colitis and Crohn's disease.
AB  - BACKGROUND AND AIM: A single nucleotide polymorphism in heat shock protein 70-2
      (HSP70-2) has been shown to be associated with a severe clinical course in
      Crohn's disease (CD), but it is not known if such a relationship exists in
      ulcerative colitis (UC). The aim of the present study was to identify
      associations between the HSP70-2 polymorphism and the clinical courses of CD and
      UC in Koreans. METHODS: Restriction fragment length polymorphism analysis was
      performed for HSP70-2 polymorphisms using the PstI-cleavage site present in the B
      allele but not in the A allele of the DNA obtained from 101 patients with CD, 144
      patients with UC, and 245 age- and sex-matched healthy controls. Study subjects
      were classified by disease behavior, severity and extent of disease. RESULTS: In
      CD, multivariate analysis showed that the AA genotype of HSP70-2 polymorphisms
      was associated with non-perforating disease (OR 10.10, 95% CI 1.66-15.38) and
      male sex (OR 3.56, 95% CI 1.04-12.23), and that the BB genotype was associated
      with severe CD (OR 12.03, 95% CI 1.60-101.56). In contrast, multivariate analysis
      for UC showed that the AA genotype was associated with severe UC (OR 2.02, 95% CI
      1.34-3.03). CONCLUSIONS: CD patients with BB genotype of HSP70-2 polymorphism
      tend to experience a more severe clinical course and allele A is associated with
      more severe UC. HSP70-2 polymorphism may be used to predict CD and UC phenotypes,
      which can illuminate immunological differences in CD and UC.

PMID- 17532783
TI  - Increased expression of non-interleukin-2 T cell growth factors and their
      implications during liver allograft rejection in rats.
AB  - BACKGROUND AND AIM: Rejection remains a problem in the transplantation field. The
      aim of this study was to establish acute and chronic rejection models in rats and
      to investigate the roles of non-interleukin (IL)-2 T cell growth factors such as
      IL-15, IL-7 and IL-13 during rejection. METHODS: A liver transplant model was
      established using Dark Agouti and Brown Norway rats. The rats were divided into
      group A, left without treatment; group B, received cyclosporinee (1 mg/kg/day);
      and group C, cyclosporinee (4 mg/kg/day). Histopathological, reverse
      transcriptase-polymerase chain reaction and western blot were performed in liver
      specimens obtained from different time-points after transplantation in the three
      groups. RESULTS: In group A, the livers showed irreversible acute cellular
      rejection with cell infiltration. In group B, chronic liver rejection was found,
      with graft infiltration, ductular damage or proliferation, obliterative
      arteriopathy and liver fibrosis. No apparent histological alterations were
      observed in group C. IL-15, IL-7 and IL-13 messenger RNA and their protein were
      all highly expressed in the liver specimens of groups A and B. Upregulated
      expression was found in IL-15 since the first day after transplantation and in IL
      7 and IL-13 since day 6. The extent of IL-15 upregulation was more than that of
      IL-7 and IL-13. CONCLUSIONS: Liver transplantation in Dark Agouti to Brown Norway
      rats with low-dose immunosuppression can induce chronic rejection. In the process
      of acute and chronic allograft rejections, non-IL-2 T cell growth factors such as
      IL-15, IL-7 and IL-13 play roles. Strategies should pay more attention to
      regulating these cytokines after liver transplantation.

PMID- 17532784
TI  - Fine-needle aspiration cytology to distinguish dysplasia from hepatocellular
      carcinoma with different grades.
AB  - BACKGROUND: Distinguishing dysplasia from hepatocellular carcinoma (HCC) by fine
      needle aspiration (FNA) cytology is difficult. The aim of this study was to
      diagnose HCC and the distinction of liver cell dysplasia from HCC with different
      grades by interpreting and scoring the cyto-morphological features. METHODS:
      Eighty-three cirrhotic patients undertook a sonography-guided FNA and subsequent
      needle biopsy for the tumor. HCC was confirmed in 68 cases and cirrhosis with
      dysplasia in 15 cases by pathology and follow-up for longer than 2 years.
      Eighteen cytological features were scored as degree of one, two or three
      according to their presence or prominence. RESULTS: Two cases of well
      differentiated HCC were diagnosed as negative for HCC initially. The sensitivity,
      specificity, false positive, false negative and accuracy were 97%, 100%, 0%, 3%
      and 97.6% for FNA cytology in the diagnosis of HCC, respectively. The score of
      dysplasia was 20.8 +/- 1.3 (mean +/- SD) and lower than 26.2 +/- 3.4 in
      Edmondson's grade I HCC (P < 0.01), 28.9 +/- 2.9 in grade II HCC (P < 0.01), and
      34.9 +/- 4.3 in grade III/IV HCC (P < 0.01). The score was also significantly
      lower in grade II HCC than in grade III/IV HCC (P < 0.01). CONCLUSIONS: FNA
      yielded a high accuracy in the distinction of dysplasia from HCC with different
      grades. There is a good correlation in cyto-morphological scores of liver cell
      dysplasia and HCC with different grades. Dysplasia displayed the lowest score and
      the score increased in order from dysplasia to grade III/IV HCC.

PMID- 17532785
TI  - Differences between right- and left-sided colon cancer in patient
      characteristics, cancer morphology and histology.
AB  - BACKGROUND AND AIM: Recently, the clinical and biological differences between
      right- and left-sided colon cancers have been widely debated. However, close
      analyses of these clinical differences, based on large-scale studies, have been
      scarcely reported. METHODS: A total of 3552 consecutive Japanese colorectal
      cancer cases were examined and the clinical differences between right- and left
      sided colon cancer cases were investigated. RESULTS: The proportion of right
      sided colon cancer was relatively high in patients aged less than 40 years (33%)
      and more than 80 years (43%). The proportion of right-sided colon cancer in
      patients aged 40-59 years was relatively low (male 22% and female 29%). In male
      patients the proportion increased in the 70-79 years age group (30%), while in
      female patients the proportion increased in the 60-69 years age group (39%).
      Right-sided colon cancer was more likely to be detected at an advanced stage (T1
      stage; left 22%, right 15%) (P < 0.01) with severe symptoms. Polypoid-type early
      cancer was dominant in the left colon (left 59%; right 40%) (P < 0.01), while the
      proportion of flat-type early cancer in the right colon was significantly higher
      than that in the left colon (left 25%; right 44%) (P < 0.01). CONCLUSIONS:
      Specific age distribution of right-sided colon cancer was observed and the
      difference between male and female patients was highlighted. Other clinical
      features also differed between right- and left-sided colon cancer, suggesting
      that different mechanisms may be at work during right and left colon
      carcinogenesis.

PMID- 17532786
TI  - Clinical outcomes of chronic hepatitis B patients with persistently detectable
      serum hepatitis B virus DNA during lamivudine therapy.
AB  - BACKGROUND AND AIM: A small proportion of chronic hepatitis B patients have
      persistently detectable serum hepatitis B virus (HBV) DNA despite lamivudine
      therapy. The incidence and clinical outcomes of patients who persistently have
      detectable serum HBV-DNA during lamivudine therapy was investigated. METHOD: We
      enrolled 221 chronic hepatitis B patients who underwent lamivudine therapy for
      more than 6 months. Among them, 180 were HBeAg positive. Serum HBV-DNA, HBeAg,
      anti-HBe and alanine aminotransferase (ALT) levels were serially monitored. The
      study groups were defined, using a hybridization assay, as patients with
      reductions in serum HBV-DNA below the detectable level (group I) or patients with
      persistently detectable serum HBV-DNA (group II) during the initial 6 months of
      lamivudine therapy. RESULTS: The incidence of patients who had persistently
      detectable HBV-DNA was 7.7%. After the first year, the rates of viral
      breakthrough, HBeAg loss and serum ALT normalization of group I versus group II
      were 21% versus 63%, 38% versus 0%, and 71% versus 28%, respectively (P < 0.001).
      The log(10) reduction of serum HBV-DNA at 6 months was -4.58 log(10) for group I
      and -1.97 log(10) for group II (P < 0.001, bDNA assay). There were no
      pretreatment lamivudine-resistant mutants in group II. CONCLUSION: Lamivudine had
      little effect on serum HBV-DNA suppression, viral breakthrough suppression and
      rate of HBeAg loss and ALT normalization in chronic hepatitis B patients with
      persistently detectable serum HBV-DNA during the initial 6 months of therapy.
      Early termination of lamivudine therapy is advocated for these patients.

PMID- 17532787
TI  - Preprodynorphin mediates locomotion and D2 dopamine and mu-opioid receptor
      changes induced by chronic 'binge' cocaine administration.
AB  - Evidence suggests that the kappa-opioid receptor (KOP-r) system plays an
      important role in cocaine addiction. Indeed, cocaine induces endogenous KOP
      activity, which is a mechanism that opposes alterations in behaviour and brain
      function resulting from repeated cocaine use. In this study, we have examined the
      influence of deletion of preprodynorphin (ppDYN) on cocaine-induced behavioural
      effects and on hypothalamic-pituitary-adrenal axis activity. Furthermore, we have
      measured mu-opioid receptor (MOP-r) agonist-stimulated [(35)S]GTPgammaS, dopamine
      D(1), D(2) receptor and dopamine transporter (DAT) binding. Male wild-type (WT)
      and ppDYN knockout (KO) mice were injected with saline or cocaine (45 mg/kg/day)
      in a 'binge' administration paradigm for 14 days. Chronic cocaine produced an
      enhancement of locomotor sensitisation in KO. No genotype effect was found on
      stereotypy behaviour. Cocaine-enhanced MOP-r activation in WT but not in KO.
      There was an overall decrease in D(2) receptor binding in cocaine-treated KO but
      not in WT mice. No changes were observed in D(1) and DAT binding. Cocaine
      increased plasma corticosterone levels in WT but not in KO. The data confirms
      that the endogenous KOP system inhibits dopamine neurotransmission and that ppDYN
      may mediate the enhancement of MOP-r activity and the activation of the
      hypothalamic-pituitary-adrenal axis after chronic cocaine treatment.

PMID- 17532788
TI  - Partial agonist actions of aripiprazole and the candidate antipsychotics S33592,
      bifeprunox, N-desmethylclozapine and preclamol at dopamine D(2L) receptors are
      modified by co-transfection of D(3) receptors: potential role of heterodimer
      formation.
AB  - Aripiprazole and the candidate antipsychotics, S33592, bifeprunox, N
      desmethylclozapine (NDMC) and preclamol, are partial agonists at D(2) receptors.
      Herein, we examined their actions at D(2L) and D(3) receptors expressed
      separately or together in COS-7 cells. In D(2L) receptor-expressing cells co
      transfected with (D(3) receptor-insensitive) chimeric adenylate cyclase-V/VI,
      drugs reduced forskolin-stimulated cAMP production by approximately 20% versus
      quinpirole (48%). Further, quinpirole-induced inhibition was blunted by
      aripiprazole and S33592, confirming partial agonist properties. In cells co
      transfected with equal amounts of D(2L)and D(3) receptors (1 : 1), efficacies of
      aripiprazole and S33592 were attenuated. Further, in cells co-transfected with
      D(2L) and an excess of D(3) receptors (1 : 3), aripiprazole and S33592 were
      completely inactive, and they abolished the actions of quinpirole. Likewise,
      bifeprunox, NDMC and preclamol lost agonist properties in cells co-transfected
      with D(2L)and D(3) receptors. Accordingly, at split D(2trunk)/D(3tail) and
      D(3trunk)/D(2tail) chimeras, agonist actions of quinpirole were blocked by
      aripiprazole and S33592 that, like bifeprunox, NDMC and preclamol, were inactive
      alone. Conversely, when a 12 amino acid sequence in the third intracellular loop
      of D(3) receptors was replaced by the homologous sequence of D(2L) receptors,
      aripiprazole, S33592, bifeprunox, NDMC and preclamol inhibited cAMP formation by
      approximately 20% versus quinpirole (42%). Moreover, at D(2L) receptor-expressing
      cells co-transfected with modified D(3i3(D2)) receptors, drugs behaved as partial
      agonists. To summarize, low efficacy agonist actions of aripiprazole, S33592,
      bifeprunox, NDMC and preclamol at D(2L) receptors are abrogated upon co
      expression of D(3) receptors, probably due to physical association and weakened
      coupling efficacy. These findings have implications for the functional profiles
      of antipsychotics.

PMID- 17532789
TI  - Ectodomain shedding of neuroglycan C, a brain-specific chondroitin sulfate
      proteoglycan, by TIMP-2- and TIMP-3-sensitive proteolysis.
AB  - Neuroglycan C (NGC) is a transmembrane-type of chondroitin sulfate proteoglycan
      with an epidermal growth factor (EGF)-like module that is exclusively expressed
      in the CNS. Because ectodomain shedding is a common processing step for many
      transmembrane proteins, we examined whether NGC was subjected to proteolytic
      cleavage. Western blotting demonstrated the occurrence of a soluble form of NGC
      with a 75 kDa core glycoprotein in the soluble fraction of the young rat
      cerebrum. In contrast, full-length NGC with a 120 kDa core glycoprotein and its
      cytoplasmic fragment with a molecular size of 35 kDa could be detected in the
      membrane fraction. The soluble form of NGC was also detectable in culture media
      of fetal rat neurons, and the full-length form existed in cell layers. The amount
      of the soluble form in culture media was decreased by adding a physiological
      protease inhibitor such as a tissue inhibitor of metalloproteinase (TIMP)-2 or
      TIMP-3, but not by adding TIMP-1. Both EGF-like and neurite outgrowth-promoting
      activity of the NGC ectodomain may be regulated by this proteolytic processing.

PMID- 17532790
TI  - Proteomic analysis of striatal proteins in the rat model of L-DOPA-induced
      dyskinesia.
AB  - L-DOPA-induced dyskinesia (LID) is among the motor complications that arise in
      Parkinson's disease (PD) patients after a prolonged treatment with L-DOPA. To
      this day, transcriptome analysis has been performed in a rat model of LID
      [Neurobiol. Dis., 17 (2004), 219] but information regarding the proteome is still
      lacking. In the present study, we investigated the changes occurring at the
      protein level in striatal samples obtained from the unilaterally 6
      hydroxydopamine-lesion rat model of PD treated with saline, L-DOPA or
      bromocriptine using two-dimensional difference gel electrophoresis and mass
      spectrometry (MS). Rats treated with L-DOPA were allocated to two groups based on
      the presence or absence of LID. Among the 2000 spots compared for statistical
      difference, 67 spots were significantly changed in abundance and identified using
      matrix-assisted laser desorption/ionization time-of-flight MS, atmospheric
      pressure matrix-assisted laser desorption/ionization and HPLC coupled tandem MS
      (LC/MS/MS). Out of these 67 proteins, LID significantly changed the expression
      level of five proteins: alphabeta-crystalin, gamma-enolase, guanidoacetate
      methyltransferase, vinculin, and proteasome alpha-2 subunit. Complementary
      techniques such as western immunoblotting and immunohistochemistry were performed
      to investigate the validity of the data obtained using the proteomic approach. In
      conclusion, this study provides new insights into the protein changes occurring
      in LID.

PMID- 17532792
TI  - Defining the gonadotrophin-releasing hormone neuronal network: transgenic
      approaches to understanding neurocircuitry.
AB  - The gonadotrophin-releasing hormone (GnRH) neurones are the final downstream
      effector neurones driving the central regulation of reproductive function and
      fertility in all mammalian species. Although it is abundantly clear that
      successful fertility relies upon the communication of a variety signals regarding
      internal and external cues to the GnRH neuronal population, how this is achieved
      remains poorly understood. A range of technical limitations has posed significant
      hurdles to defining, with any certainty, the complexities of the synaptic
      neuronal network regulating GnRH neurones. However, recent advances in transgenic
      technology have opened up new avenues to reconsider questions aimed at
      understanding this critical network. This article addresses some of the latest
      advances that use transgenic mouse models as tools to understand the neuronal
      circuitry underpinning the regulation of the GnRH neurones. By incorporating
      standard morphological and viral tract tracing techniques with innovative
      transgenic tools, recent studies have uncovered previously unappreciated
      qualities of the GnRH neurone, including extensive dendritic lengths, numerous
      somal and dendritic spines and plasticity over pubertal development, along with
      beginning to define the primary and higher-order afferents that make up the GnRH
      neuronal network.

PMID- 17532791
TI  - Multiple effects of 2ME2 and D609 on the cortical expression of HIF-1alpha and
      apoptotic genes in a middle cerebral artery occlusion-induced focal ischemia rat
      model.
AB  - Despite 2-methoxyestradiol (2ME2) and tricyclodecan-9-yl-xanthogenate (D609)
      having multiple effects on cancer cells, mechanistically, both of them down
      regulate hypoxia-inducible factor-1alpha (HIF-1alpha) and vascular endothelial
      growth factor (VEGF). We hypothesize HIF-1alpha plays an essential role in
      cerebral ischemia as a pro-apoptosis regulator; 2ME2 and D609 decrease the levels
      of HIF-1alpha and VEGF, that might contribute to protecting brain from ischemia
      injury. A total of 102 male Sprague-Dawley rats were split into five groups:
      sham, middle cerebral artery occlusion (MCAO), MCAO + dimethyl sulfoxide, MCAO +
      2ME2, and MCAO + D609. 2ME2 and D609 were injected intraperitoneally 1 h after
      reperfusion. Rats were killed at 24 h and 7 days. At 24 h, 2ME2 and D609 reduce
      the levels of HIF-1alpha and VEGF (enzyme-linked immunosorbent assay), depress
      the expression of HIF-1alpha, VEGF, BCL2/adenovirus E1B 19 kDa interacting
      protein 3 (BNIP3) and cleaved caspase 3 (western blot and immunohistochemistry)
      in the brain infarct area. Double fluorescence labeling shows HIF-1alpha positive
      immunoreactive materials are co-localized with BNIP3 and terminal
      deoxynucleotidyl transferase biotin-dUTP nick end labeling inside the nuclei of
      neurons. At 7 days, 2ME2 and D609 reduce the infarct volume (2,3,7
      triphenyltetrazolium chloride) and blood-brain barrier extravasation, decrease
      the mortality and improve the neurological deficits. In conclusion, 2ME2 and D609
      are powerful agents to protect brain from cerebral ischemic injury by inhibiting
      HIF-1alpha expression, attenuating the superfluous expression of VEGF to avoid
      blood-brain barrier disruption and suppressing neuronal apoptosis via BNIP3
      pathway.

PMID- 17532793
TI  - Identification of central nervous system sites involved in the water diuresis
      response elicited by central microinjection of nociceptin/ Orphanin FQ in
      conscious rats via c-Fos and inducible cAMP early repressor immunocytochemistry.
AB  - Intracerebroventricular (i.c.v.) administration of the opioid-like peptide,
      nociceptin/Orphanin (nociceptin), in conscious rats produces diuretic and
      antinatriuretic effects. The present study utilised changes in Fos and inducible
      cAMP early repressor (ICER) immunocytochemistry expression to examine the central
      nervous (CNS) sites activated or inhibited, respectively, by central
      administration of nociceptin. Urine samples were collected during control (15
      min) and after i.c.v. vehicle (5 microl, n = 12) or nociceptin (10 microg/5
      microl; n = 12). Four additional urine samples (15-min) were collected after the
      i.c.v. injection. The brain was processed for Fos using a commercially available
      antibody (Oncogene AB-5) and for ICER using a polyclonal anti-ICER antibody
      raised in rabbits. In vehicle-injected conscious rats, renal excretion of water
      or sodium was not altered. However, nociceptin produced a rapid and marked
      increase in urine flow (V) and a decrease in urinary sodium excretion rate. In
      addition, i.c.v. nociceptin produced a significant increase in Fos staining in
      the dorsomedial nucleus of the hypothalamus, the perinuclear zone of the
      supraoptic nucleus, the organum vasculosum of the lamina terminalis (OVLT), the
      lateral preoptic area and the lateral hypothalamic area compared to control. By
      contrast, Fos expression decreased in the area postrema and locus coeruleus
      compared to controls. Furthermore, ICER staining was significantly increased in
      the perinuclear zone of the supraoptic nucleus, supraoptic nucleus, median
      preoptic nucleus, OVLT, medial preoptic area, central nucleus of the amygdala,
      and medial nucleus of the solitary tract. Together, central opioid receptor-like
      type 1 activation in these CNS regions may participate in the neural pathways
      involved in the diuretic and antinatriuretic effects of nociceptin.

PMID- 17532794
TI  - Direct pituitary effects of kisspeptin: activation of gonadotrophs and
      somatotrophs and stimulation of luteinising hormone and growth hormone secretion.
AB  - Recent, compelling evidence indicates that kisspeptins, the products of KiSS-1
      gene, and their receptor GPR54, represent key elements in the neuroendocrine
      control of reproduction, and that they act primarily by regulating gonadotrophin
      releasing hormone (GnRH) secretion at the hypothalamus. Conversely, and despite
      earlier reports showing GPR54 expression in the pituitary, the potential
      physiological roles of kisspeptins at this gland have remained elusive. To
      clarify this issue, cultures of rat pituitary cells were used to evaluate
      expression of KiSS-1 and GPR54, and to monitor the ability of kisspeptin-10 to
      stimulate Ca(2+) responses in gonadotrophs and to elicit luteinising hormone (LH)
      secretion in vitro. The results obtained show that both GPR54 and KiSS-1 are
      expressed in the pituitary of peripubertal male and female rats. Moreover,
      kisspeptin-10 induced a rise in free cytosolic Ca(2+) concentration ([Ca(2+)](i))
      in approximately 10% of male rat pituitary cells. Intriguingly, kisspeptin
      responsive cells included not only gonadotrophs, in which a 62.8 +/-
      16.0%[Ca(2+)](i) rise was observed, but also somatotrophs, wherein kisspeptin
      induced a 60.3 +/- 5.5%[Ca(2+)](i) increase. Accordingly, challenge of dispersed
      pituitary cells with increasing kisspeptin-10 concentrations induced dose-related
      LH and growth hormone (GH) secretory responses, which were nevertheless of lower
      magnitude than those evoked by the primary regulators GnRH and GH-releasing
      hormone, respectively. In particular, 10(-8) M kisspeptin caused maximal
      increases in LH release (218.7 +/- 23.6% and 180.4 +/- 7.2% in male and female
      rat pituitary cells, respectively), and also stimulated maximally GH secretion
      (181.9 +/- 14.9% and 260.2 +/- 15.9% in male and female rat pituitary cells,
      respectively). Additionally, moderate summation of kisspeptin- and GnRH-induced
      LH responses was observed after short-term incubation of male rat pituitary
      cells. In conclusion, our results provide unequivocal evidence that kisspeptins
      exert direct pituitary effects in peripubertal male and female rats and suggest a
      possible autocrine/paracrine mode of action. The precise relevance and underlying
      mechanisms of this potential new actions of kisspeptins (i.e. the direct
      modulation of gonadotrophic and somatotrophic axis at the pituitary) deserve
      further analysis.

PMID- 17532795
TI  - Sex differences in neurotransmission parameters in response to repeated mild
      restraint stress exposures in intact male, female and ovariectomised female rats.
AB  - The present study determined whether a repeated mild restraint stress exposure
      would differentially alter neuronal activity in male and female rats to gain
      insights into neurobiological substrates involved in sex differences in stress
      induced behavioural responses. In our first set of experiments, we used Western
      blot analysis to determine whether alterations in several synaptic proteins were
      elicited by the repeated stress treatment. We found bidirectional changes in
      synaptophysin levels in female cerebral cortex and hippocampus that diverged
      between intact and ovariectomised females. There were persistent elevations in
      spinophilin levels in the male, but not female, hippocampus following the
      repeated mild restraint stress exposure. By contrast, levels of the NMDA receptor
      scaffolding protein, PSD-95, were altered only in intact female cerebral cortex
      and ovariectomised female hippocampus. We next used immunohistochemical
      evaluation of Fos expression as a marker for neuronal activation. We found
      significant increases in Fos immunoreactivity in all sex conditions across
      multiple brain regions in response to the repeated mild stress. Fos protein
      induction was greatest in the frontal cortex, piriform cortex and amygdala, with
      the degree of induction varying by sex condition. Fos induction was dramatically
      higher in amygdala and piriform cortex only in intact females following repeated
      stress compared to a single restraint stress exposure, suggestive of
      sensitisation rather than habituation. By contrast, the frontal cortex of intact
      and ovariectomised females showed habituation to the repeated stressor. Males
      displayed modest sensitisation in both the frontal cortex and dentate gyrus with
      no changes in other brain areas. Taken together, these findings show that
      exposure to a mild repeated stress results in sex differences in synaptic
      adaptations and patterns of brain activation that likely contribute to observed
      sex differences in stress-induced behaviours. This approach provides valuable
      insights into interactions between the hormonal milieu and responses to a
      repeated mild stress, and further supports the importance of considering hormonal
      status in treatment of stress-related disorders.

PMID- 17532796
TI  - Expression of the hypothalamic transcription factor Nhlh2 is dependent on energy
      availability.
AB  - Mice with a deletion of the hypothalamic basic helix-loop-helix transcription
      factor Nhlh2 display adult onset obesity, implicating Nhlh2 in the neuronal
      circuits regulating energy availability. Nhlh2 colocalises with the hypothalamic
      thyrotrophin-releasing hormone (TRH) neurones in the paraventricular nucleus
      (PVN) and pro-opiomelanocortin (POMC) neurones in the arcuate nucleus. We show
      that Nhlh2 expression is significantly reduced in response to 24-h food
      deprivation in the arcuate nucleus, PVN, lateral hypothalamus, ventromedial
      hypothalamus (VMH) and dorsomedial hypothalamus (DMH). Food intake for 2 h
      following deprivation stimulates Nhlh2 expression in the arcuate nucleus and the
      PVN, and leptin injection following deprivation results in increased Nhlh2
      expression in the arcuate nucleus, PVN, lateral hypothalamus, VMH, and DMH.
      Hypothalamic Nhlh2 expression in response to leptin injection is maximal by 2 h.
      Following leptin injection, Nhlh2 mRNA colocalises in POMC neurones in the
      arcuate nucleus and TRH neurones in the PVN. Nhlh2 mRNA expression in POMC
      neurones in the arcuate nucleus and TRH neurones in the PVN is reduced with
      energy deprivation and is stimulated with food intake and leptin injection.
      Modulation of POMC expression in response to changes in energy availability is
      not affected in mice with a targeted deletion of Nhlh2. However, deletion of
      Nhlh2 does result in loss of normal TRH mRNA expression in mice exposed to food
      deprivation and leptin stimulation. These data implicate Nhlh2 as a regulatory
      target of the leptin-mediated energy availability network of the hypothalamus,
      and TRH as a putative downstream target of Nhlh2.

PMID- 17532797
TI  - microMRI-HREM pipeline for high-throughput, high-resolution phenotyping of murine
      embryos.
AB  - Rapid and precise phenotyping analysis of large numbers of wild-type and mutant
      mouse embryos is essential for characterizing the genetic and epigenetic factors
      regulating embryogenesis. We present a novel methodology that permits precise
      high-throughput screening of the phenotype of embryos with both targeted and
      randomly generated mutations. To demonstrate the potential of this methodology we
      show embryo phenotyping results produced in a large-scale ENU-mutagenesis study.
      In essence this represents an analysis pipeline, which starts with simultaneous
      micro-magentic resonance imaging (microMRI) screening (voxel size: 25.4 x 25.4 x
      24.4 microm) of 32 embryos in one run. Embryos with an indistinct phenotype are
      then cut into parts and suspect organs and structures are analysed with HREM
      (high-resolution episcopic microscopy). HREM is an imaging technique that employs
      'positive' eosin staining and episcopic imaging for generating three-dimensional
      (3D) high-resolution (voxel size: 1.07 x 1.07 x 2 microm) digital data of near
      histological contrast and quality. The results show that our method guarantees
      the rapid availability of comprehensive phenotype information for high numbers of
      embryos in, if necessary, histological quality and detail. The combination of
      high-throughput microMRI with HREM provides an alternative screening pipeline
      with advantages over existing 3D phenotype screening methods as well as
      traditional histology. Thus, the microMRI-HREM phenotype analysis pipeline
      recommends itself as a routine tool for analysing the phenotype of transgenic and
      mutant embryos.

PMID- 17532798
TI  - An immunohistochemical study of the triangular fibrocartilage complex of the
      wrist: regional variations in cartilage phenotype.
AB  - The triangular fibrocartilage complex (TFCC) transmits load from the wrist to the
      ulna and stabilizes the distal radioulnar joint. Damage to it is a major cause of
      wrist pain. Although its basic structure is well established, little is known of
      its molecular composition. We have analysed the immunohistochemical labelling
      pattern of the extracellular matrix of the articular disc and the meniscal
      homologue of the TFCC in nine elderly individuals (age range 69-96 years), using
      a panel of monoclonal antibodies directed against collagens, glycosaminoglycans,
      proteoglycans and cartilage oligomeric matrix protein (COMP). Although many of
      the molecules (types I, III and VI collagen, chondroitin 4 sulphate, dermatan
      sulphate and keratan sulphate, the oversulphated epitope of chondroitin 6
      sulphate, versican and COMP) were found in all parts of the TFCC, aggrecan, link
      protein and type II collagen were restricted to the articular disc and to
      entheses. They were thus not a feature of the meniscal homologue. The shift in
      tissue phenotype within the TFCC, from a fibrocartilaginous articular disc to a
      more fibrous meniscal homologue, correlates with biomechanical data suggesting
      that the radial region is stiff and subject to considerable stress concentration.
      The presence of aggrecan, link protein and type II collagen in the articular disc
      could explain why the TFCC is destroyed in rheumatoid arthritis, given that it
      has been suggested that autoimmunity to these antigens results in the destruction
      of articular cartilage. The differential distribution of aggrecan within the TFCC
      is likely to be reflected by regional differences in water content and mobility
      on the radial and ulnar side. This needs to be taken into account in the design
      of improved MRI protocols for visualizing this ulnocarpal complex of the wrist.

PMID- 17532799
TI  - Epidermal differentiation in embryos of the tuatara Sphenodon punctatus
      (Reptilia, Sphenodontidae) in comparison with the epidermis of other reptiles.
AB  - Studying the epidermis in primitive reptiles can provide clues regarding
      evolution of the epidermis during land adaptation in vertebrates. With this aim,
      the development of the skin of the relatively primitive reptile Sphenodon
      punctatus in representative embryonic stages was studied by light and electron
      microscopy and compared with that of other reptiles previously studied. The
      dermis organizes into a superficial and deep portion when the epidermis starts to
      form the first layers. At embryonic stages comparable with those of lizards, only
      one layer of the inner periderm is formed beneath the outer periderm. This also
      occurs in lizards and snakes so far studied. The outer and inner periderm form
      the embryonic epidermis and accumulate thick, coarse filaments (25-30 nm thick)
      and sparse alpha-keratin filaments as in other reptiles. Beneath the embryonic
      epidermis an oberhautchen and beta-cells form small horny tips that represent
      overlapping borders along the margin of beta-cells that overlap other beta-cells
      (in a tile-like arrangement). The tips resemble those of agamine lizards but at a
      small scale, forming a lamellate-spinulated pattern as previously described in
      adult epidermis. The embryonic epidermis matures by the dispersion of coarse
      filaments among keratin at the end of embryonic development and is shed around
      hatching. The presence of these matrix organelles in the embryonic epidermis of
      this primitive reptile further indicates that amniote epidermis acquired
      interkeratin matrix proteins early for land adaptation. Unlike the condition in
      lizards and snakes, a shedding complex is not formed in the epidermis of
      embryonic S. punctatus that is like that of the adult. Therefore, as in
      chelonians and crocodilians, the epidermis of S. punctatus also represents an
      initial stage that preceded the evolution of the shedding complex for moulting.

PMID- 17532800
TI  - Comparative anatomy of the foramen ovale in the hearts of cetaceans.
AB  - The structure of the cardiac foramen ovale from 17 species representing six
      cetacean families, the Monodontidae, Phocoenidae, Delphinidae, Ziphiidae,
      Balaenidae and the Balaenopteridae, was studied using the scanning electron
      microscope. Eight white whale fetuses (Delphinapterus leucas) and a narwhal fetus
      (Monodon monoceros) represented the Monodontidae; one fetal and nine neonatal
      harbour porpoises (Phocoena phocoena) and a finless porpoise fetus (Neophocoena
      phocoenoides) represented the Phocoenidae; two white-beaked dolphin fetuses
      (Lagenorhynchus albirostris), four fetal and one neonatal Atlantic white-sided
      dolphins (Lagenorhynchus acutus), a Risso's dolphin fetus (Grampus griseus), two
      common bottle-nosed dolphin neonates (Tursiops truncatus), a female short-beaked
      common dolphin fetus (Delphinus delphis), four killer whale fetuses (Orcinus
      orca) and two long-finned pilot whale fetuses (Globicephala melas) represented
      the Delphinidae; two northern bottlenose whale fetuses (Hyperoodon ampullatus)
      represented the Ziphiidae; one bowhead whale fetus (Balaena mysticetus)
      represented the Balaenidae and five Common minke whale fetuses (Balaenoptera
      acutorostrata), one blue whale fetus (Balaenoptera musculus), nine fin whale
      fetuses (Balaenoptera physalus) and four humpback whale fetuses (Megaptera
      novaeangliae) represented the Balaenopteridae. The hearts of an additional two
      incompletely identified toothed and four baleen whale fetuses were also studied.
      In each species the fold of tissue derived from the cardiac septum primum and
      subtended by the foramen ovale had the appearance of a short tunnel or sleeve
      which was fenestrated at its distal end. In the toothed whales the tissue fold
      was tunnel-shaped with the interatrial septum as the floor whereas in baleen
      whales it was more sleeve-like. In toothed whales thin threads extended from the
      fold to insert into the interatrial septum whereas a network of threads covered
      the distal end of the sleeve in the baleen whales. Similar structures were
      present in the corresponding cardiac tissues of neonatal Hippopotamidae.

PMID- 17532801
TI  - Does emotion modulate the blink reflex in human conditioning? Startle
      potentiation during pleasant and unpleasant cues in the picture-picture paradigm.
AB  - Emotional processes modulate the size of the eyeblink startle reflex in a picture
      viewing paradigm, but it is unclear whether emotional processes are responsible
      for blink modulation in human conditioning. Experiment 1 involved an aversive
      differential conditioning phase followed by an extinction phase in which acoustic
      startle probes were presented during CS+, CS-, and intertrial intervals. Valence
      ratings and affective priming showed the CS+ was unpleasant postacquisition.
      Blink startle magnitude was larger during CS+ than during CS-. Experiment 2 used
      the same design in two groups trained with pleasant or unpleasant pictorial USs.
      Ratings and affective priming indicated that the CS+ had become pleasant or
      unpleasant in the respective group. Regardless of CS valence, blink startle was
      larger during CS+ than CS- in both groups. Thus, startle was not modulated by CS
      valence.

PMID- 17532802
TI  - Auditory temporal grouping in newborn infants.
AB  - Adults normally perceive auditory scenes in terms of sound patterns emitted by
      concurrently active sources. Thus pattern formation is an important process of
      auditory object perception. The aim of the present study was to determine whether
      neonates group sounds by repeating pitch patterns. Standard ("S"; p=80%) and
      deviant tones ("D", p=20%) differing only in pitch were delivered either in a
      randomized order (random condition) or in a repeating SSSSD pattern (grouped
      condition). Both event-related brain potentials and gamma-band activity differed
      between the S and D tones in the random condition but not in the grouped
      condition. These results suggest that in the grouped condition, the S and D tones
      were processed as part of the same higher order regularity by the neonate
      auditory system. Also, for the first time, we observed oscillatory gamma-band
      activity in neonates, which was sensitive to infrequent pitch changes.

PMID- 17532803
TI  - Anterior N2 predicts subsequent viewing time and interest rating for novel
      drawings.
AB  - Event-related brain potentials (ERPs) in response to novel pictures and
      subsequent visual exploration were examined. Eighteen undergraduates viewed 120
      novel drawings as long as they wished. ERPs were calculated separately for
      drawings that were viewed longer or shorter than the median viewing time of each
      participant. The drawings viewed longer elicited a larger anterior negativity
      (N2) peaking at 245 ms than the shorter viewed drawings. This effect disappeared
      and the overall amplitude of the N2 decreased when the same set of drawings was
      presented again in a subsequent interest-rating session. Drawings rated as more
      interesting elicited a larger N2 than did drawings rated as less interesting.
      This study demonstrates a type of anterior N2 that is sensitive to stimulus
      unfamiliarity or difficulty in encoding, which reflects a conflict between
      stimulus input and existing knowledge and prompts further recognition processes
      and visual exploration.

PMID- 17532804
TI  - Mood effects on autonomic activity in mood regulation.
AB  - University students (N=43) watched film clips to manipulate negative, neutral, or
      positive mood states and then performed a mood regulation task with the goal of
      experiencing positive affect. Autonomic reactivity was assessed during
      habituation, mood inductions, and mood regulation. According to the mood-behavior
      model (G.H.E. Gendolla, 2000) and studies on self-regulation, we predicted
      stronger cardiovascular and electrodermal reactivity in a negative mood than in
      both positive and neutral moods in the context of mood regulation but not during
      the mood inductions. Results were as expected. Furthermore, the Zygomaticus Major
      muscle reacted more strongly in the positive than in the neutral and negative
      mood conditions during the mood inductions. The findings are interpreted as
      demonstrating mood effects on resource mobilization during an effortful mood
      regulation performance.

PMID- 17532805
TI  - N1 and the mismatch negativity are spatiotemporally distinct ERP components:
      disruption of immediate memory by auditory distraction can be related to N1.
AB  - Event-related potentials (ERPs) were recorded for ignored tones presented during
      the retention interval of a delayed serial recall task. The mismatch negativity
      (MMN) and N1 ERP components were measured to discern spatiotemporal and
      functional properties of their generation. A nine-token sequence with nine
      different tone pitches was more disruptive than an oddball (two-token) sequence,
      yet this oddball sequence was no more disruptive than a single repeating tone
      (one-token). Tones of the nine-token sequence elicited augmented N1 amplitudes
      compared to identical tones delivered in the one-token sequence, yet deviants
      elicited an additional component (MMN) with distinct temporal properties and
      topography. These results suggested that MMN and N1 are separate, functionally
      distinct components. Implications are discussed for the N1 hypothesis and the
      changing-state hypothesis of the disruption of serial recall performance by
      auditory distraction.

PMID- 17532806
TI  - Use of ephedrine and dopamine in dogs for the management of hypotension in
      routine clinical cases under isoflurane anesthesia.
AB  - OBJECTIVE: To determine the cardiovascular responses of ephedrine and dopamine
      for the management of presurgical hypotension in anesthetized dogs. STUDY DESIGN:
      Prospective, randomized, clinical trial. ANIMALS: Twelve healthy client-owned
      dogs admitted for orthopedic surgery; six per group METHODS: Prior to surgery, 58
      anesthetized dogs were monitored for hypotension [mean arterial pressure (MAP)
      <60 mmHg] that was not associated with bradycardia or excessive anesthetic depth.
      Ephedrine (0.2 mg kg(-1), IV) or dopamine (5 microg kg(-1) minute(-1), IV) was
      randomly assigned for treatment in 12 hypotensive dogs. Ten minutes after the
      first treatment (Tx(1)-10), ephedrine was repeated or the dopamine infusion rate
      was doubled. Cardiovascular assessments taken at baseline, Tx(1)-10, and 10
      minutes following treatment adjustment (Tx(2)-10) were compared for differences
      within and between treatments (p < 0.05). RESULTS: Ephedrine increased cardiac
      index (CI), stroke volume index (SVI), oxygen delivery index (DO(2)I), and
      decreased total peripheral resistance (TPR) by Tx(1)-10, while MAP increased
      transiently (<5 minutes). The second ephedrine bolus produced no further
      improvement. Dopamine failed to produce significant changes at 5 microg kg(-1)
      minute(-1), while 10 microg kg(-1) minute(-1) increased MAP, CI, SVI
      significantly from baseline, and DO(2)I compared with Tx(1)-10. The improvement
      in CI, SVI, and DO(2)I was not significantly different between treatments at
      Tx(2)-10. CONCLUSIONS AND CLINICAL RELEVANCE: In anesthetized hypotensive dogs,
      ephedrine and dopamine improved cardiac output and oxygen delivery. However, the
      pressure-elevating effect of ephedrine is transient, while an infusion of
      dopamine at 10 microg kg(-1) minute(-1) improved MAP significantly by
      additionally maintaining TPR.

PMID- 17532810
TI  - A cost-effectiveness decision model for antiepileptic drug treatment in newly
      diagnosed epilepsy patients.
AB  - OBJECTIVE: To establish cost-effectiveness of antiepileptic drug (AED) treatment
      strategies of newly diagnosed patients with epilepsy. METHODS: A decision
      analysis was carried out comparing effectiveness and treatment cost of six
      treatment strategies comprising carbamazepine (CBZ), lamotrigine (LTG), and
      valproate (VPA) as first-line and second-line drugs. Three outcome groups were
      defined: complete success, partial success, and failure. Data on seizure control
      and failure due to adverse effects were derived from the literature. Data on
      resource use and costs were collected for each outcome group by means of a
      patient survey. RESULTS: Cost data were obtained from 71 patients. Cost increased
      from complete success to failure outcome groups. The probability of obtaining
      complete success varied from 64% (VPA-CBZ strategy) to 74% (LTG-VPA strategy).
      The strategy LTG-VPA was more effective than the least expensive strategy CBZ
      VPA, but at higher costs per additional effectively treated patient.
      Probabilistic sensitivity analysis confirmed these findings to be robust.
      Subsequent analysis showed that changing inclusion criteria used in the selection
      of the studies from the literature had a major effect on cost-effectiveness
      ratios of the various strategies. The probability that LTG first-line therapy is
      the most cost-effective option remains small, even defining a high cost
      effectiveness threshold. Nevertheless, LTG second-line strategies can be cost
      effective depending on the willingness to pay for patient improvement.
      CONCLUSIONS: Only a few studies satisfied our inclusion criteria for employment
      in our decision model. Our model supports the use of conventional AEDs as first
      line options for patients with newly diagnosed epilepsy. LTG second-line therapy
      is likely to be the most cost-effective option in case society is willing to pay
      more than Euro 6000 for an additional successfully treated patient. This study
      also illustrates that, with the data presently available, the outcome of decision
      analysis for AED treatment choice depends on the inclusion criteria used to
      select trials. Prospective real-life studies are needed in which first- and
      second-line treatment strategies are compared with respect to both effectiveness
      and costs.

PMID- 17532811
TI  - A systematic review evaluating health-related quality of life, work impairment,
      and health-care costs and utilization in abnormal uterine bleeding.
AB  - OBJECTIVES: Abnormal uterine bleeding (AUB) impacts women's health-related
      quality of life (HRQoL) and puts a heavy economic burden on society. To date,
      this burden has not been systematically studied. We conducted a systematic review
      of the medical literature to evaluate the impact of AUB on HRQoL and to quantify
      the economic burden of AUB from a societal perspective. METHODS: We searched the
      PubMed and Cochrane databases, and article bibliographies for the period up to
      July 2005. Teams of two reviewers independently abstracted data from studies that
      reported outcomes of interest: prevalence, HRQoL, work impairment, and health
      care utilization and costs associated with AUB. RESULTS: The search yielded 1009
      English-language articles. Ninety-eight studies (including randomized controlled
      trials, observational studies, and reviews) that met the inclusion and exclusion
      criteria underwent a full-text review. The prevalence of AUB among women of
      reproductive age ranged from 10% to 30%. The HRQoL scores from the 36-item Short
      Form Health Survey Questionnaire (SF-36) suggested that women with AUB have HRQoL
      below the 25th percentile of that for the general female population within a
      similar age range. The conservatively estimated annual direct and indirect
      economic costs of AUB were approximately $1 billion and $12 billion,
      respectively. These figures do not account for intangible costs and productivity
      loss due to presenteeism. CONCLUSIONS: The burden of AUB needs further and more
      thorough investigation. Additional research should prospectively evaluate the
      impact of AUB and the value of treatment provided to help guide future health
      resource allocation and clinical decision-making.

PMID- 17532812
TI  - Eliciting expert opinion for economic models: an applied example.
AB  - OBJECTIVES: Expert opinion is considered as a legitimate source of information
      for decision-analytic modeling where required data are unavailable. Our objective
      was to develop a practical computer-based tool for eliciting expert opinion about
      the shape of the uncertainty distribution around individual model parameters.
      METHODS: We first developed a prepilot survey with departmental colleagues to
      test a number of alternative approaches to eliciting opinions on the shape of the
      uncertainty distribution around individual parameters. This information was used
      to develop a survey instrument for an applied clinical example. This involved
      eliciting opinions from experts to inform a number of parameters involving
      Bernoulli processes in an economic model evaluating DNA testing for families with
      a genetic disease, hypertrophic cardiomyopathy. The experts were cardiologists,
      clinical geneticists, and laboratory scientists working with cardiomyopathy
      patient populations and DNA testing. RESULTS: Our initial prepilot work suggested
      that the more complex elicitation techniques advocated in the literature were
      difficult to use in practice. In contrast, our approach achieved a reasonable
      response rate (50%), provided logical answers, and was generally rated as easy to
      use by respondents. The computer software user interface permitted graphical
      feedback throughout the elicitation process. The distributions obtained were
      incorporated into the model, enabling the use of probabilistic sensitivity
      analysis. CONCLUSION: There is clearly a gap in the literature between
      theoretical elicitation techniques and tools that can be used in applied decision
      analytic models. The results of this methodological study are potentially
      valuable for other decision analysts deriving expert opinion.

PMID- 17532813
TI  - Estimating the rate of accumulating drug resistance mutations in the HIV genome.
AB  - OBJECTIVE: HIV mutation accumulation has great implications for pharmacoeconomics
      and clinical care, yet scarcity of data has hindered its representation in
      decision analytic models. Our objective is to determine the accuracy with which
      mutation accumulation and other unmeasured parameters could be estimated during
      model calibration. METHODS: We used a second-order Monte Carlo simulation of HIV
      natural history that had been calibrated by varying two unmeasured parameters
      (mutation accrual rate and probability of adherence) to minimize differences
      between estimated and observed clinical outcomes (time to treatment failure and
      survival). We compared these estimated values first with only those results that
      had been already published at the time of model calibration, and second including
      results that were published after model calibration. RESULTS: The value for
      mutation accrual rate assigned during calibration was 0.014 mutations per month
      for antiretroviral-naive patients, at the lower bound of the results for nine
      heterogeneous studies published at the time of calibration (pooled 95% confidence
      interval [CI] 0.014-0.039 mutations per month). In contrast, this estimate
      accurately anticipated results from 11 larger and more homogeneous studies
      published after calibration (pooled 95% CI for antiretroviral-naive patients,
      0.012-0.015 mutations per month). The value for probability of adherence assigned
      during calibration (75%) was also within the range of published results (pooled
      95% CI 62-76%). CONCLUSION: Estimates for unobserved parameters derived during
      model calibration were not only within the range of clinical observations, but
      anticipated with accuracy clinical results that were not yet available. It may be
      feasible to use models to estimate unobserved parameters.

PMID- 17532814
TI  - Mapping from disease-specific measures to utility: an analysis of the
      relationships between the Inflammatory Bowel Disease Questionnaire and Crohn's
      Disease Activity Index in Crohn's disease and measures of utility.
AB  - OBJECTIVES: To examine the relationship between the Inflammatory Bowel Disease
      Questionnaire (IBDQ), Crohn's Disease Activity Index (CDAI) and measures of
      utility (EQ-5D and the SF-6D indexes), and to estimate algorithms to map the two
      utility values from IBDQ and CDAI scores. METHODS: A large data set from clinical
      trials in Crohn's disease provided contemporaneous patient responses to all four
      questionnaires. Paired observations from multiple time-points were analyzed. We
      calculated mean utility scores by IBDQ and CDAI score deciles; Spearman
      correlation coefficients for paired observations between IBDQ and EQ-5D (n =
      3320) and IBDQ and SF-6D (n = 3230), and explored regression models using maximum
      likelihood estimation. The IBDQ/SF-6D model was validated against paired
      observations from an independent data set. RESULTS: The IBDQ decile analysis
      demonstrated a consistent positive relationship with both utility indexes.
      Correlations between the IBDQ and both the EQ-5D and SF-6D were statistically
      significant (P < 0.0001), with correlation coefficients of 0.76 and 0.85,
      respectively. A simple linear model between EQ-5D and IBDQ explained 45% of the
      variance. The residuals plot for the IBDQ/SF-6D model suggested some nonlinearity
      and a nonlinear model explained 69% of the variance. In the validation analysis,
      no statistically significant difference was observed between the mean observed SF
      6D and the SF-6D scores estimated using the IBDQ/SF-6D regression model.
      CONCLUSIONS: Given the strength, consistency, and predictable characteristics of
      the relationships, the algorithms appear to provide valuable and valid methods to
      estimate utilities from IBDQ scores (but not CDAI) in trials of Crohn's disease
      patients that have collected IBDQ scores but not utilities.

PMID- 17532815
TI  - Substantial treatment overuse in the United States?

PMID- 17532817
TI  - Management of inflammatory bowel disease in adults.
AB  - Optimal care of the inflammatory bowel diseases, Crohn's disease and ulcerative
      colitis, requires a broad understanding of disease pathophysiology and
      therapeutic alternatives. The goals of therapy are accurate diagnosis and timely
      treatment to both induce and maintain a clinical remission and improve patient
      quality of life. Most patients can be adequately treated using a combination or
      aminosalicylates, antibiotics, and corticosteroids, though many patients with
      Crohn's disease will require immunomodulators, such as azathioprine or 6
      mercaptopurine. The development of novel biologic therapies, particularly
      infliximab, have dramatically improved our ability to medically manage more
      severe Crohn's disease and ulcerative colitis patients. This review will focus on
      the medical management of inflammatory bowel disease in adults.

PMID- 17532818
TI  - Factors affecting the serum gastrin 17 level: an evidence-based analysis of 3906
      serum samples among Chinese.
AB  - OBJECTIVE: To investigate the influence of gender, age, site of lesion, disease
      type and Helicobacter pylori (H. pylori) infection on the human serum gastrin-17
      level and to study the diagnostic value of serum gastrin-17 in gastric
      precancerous lesions and gastric cancer. METHODS: Serum gastrin-17 and serum H.
      pylori IgG antibody were detected by the ELISA method. The different gastric
      disease groups were confirmed by endoscopy and histopathology. RESULTS: Among the
      3906 serum samples according to the gender, age, site of lesion and the data of
      different gastric disease groups, the serum gastrin-17 level was markedly higher
      in people>or=60 years old than that in younger age groups. The serum gastrin-17
      level increased progressively in the following order: healthy control group,
      nonatrophic gastritis group, gastric ulcer group, and the serum gastrin-17 level
      was higher in the atrophic gastritis with dysplasia group than that without it,
      the lowest level being in the gastric cancer group. Among the 2946 serum samples
      matched with the site of the lesion, the serum gastrin-17 level was higher in
      those with antral diseases than in those with gastric corpus diseases. Among the
      3805 serum samples matched with the H. pylori infection data, the serum gastrin
      17 level was higher in the H. pylori-positive group than in the H. pylori
      negative group. CONCLUSIONS: In people over 60 years of age, the serum gastrin-17
      level tends to increase. In subjects with precancerous gastric lesions, it may
      increase significantly with the progression of gastric disease, and ultimately
      decrease in gastric cancer. Serum gastrin-17 is a good biomarker to differentiate
      benign from malignant gastric diseases. The site of the gastric lesions is an
      important factor affecting the serum gastrin-17 level, whereas H. pylori
      infection is usually associated with its increment.

PMID- 17532819
TI  - Colonoscopy in elderly Asians: a prospective evaluation in routine clinical
      practice.
AB  - OBJECTIVE: Colonoscopy is believed to be more complicated in elderly patients in
      Western countries. It is uncertain if the situation holds true among Asians. This
      study is to determine differences in colonoscopy performance and sedation
      complications between patients aged<65 years and those>or=65 years of age in an
      Asian population. METHODS: A prospective, cross-sectional study of adults
      attending outpatient colonoscopy at a tertiary institution. Clinical and
      endoscopic data were obtained from all consenting adults. RESULTS: Two hundred
      and one patients (70 elderly and 131 aged<65 years) were enrolled. Compared to
      the patients aged<65 years, the elderly patients had similar levels of good
      (42.9%vs 45.8%), satisfactory (42.9%vs 33.6%) and poor (14.3%vs 20.6%) bowel
      preparations (P=NS). Cecal intubation was achieved in 60 (85.7%) of the elderly
      patients and 116 (88.5%) of the younger adults (P=NS). The differences in mean
      total colonoscopy duration was not significant (30+/-13 vs 27+/-11 min). Although
      the elderly patients received lower mean sedation doses of midazolam (4.7 vs 5.1
      mg) and pethidine (37.8 vs 46.4 mg) compared to the younger adults, the
      hypotension rates were significantly higher in the elderly patients (7.1%vs 0.8%,
      P=0.01). The elderly patients had in additional one or more co-morbid illnesses
      (P=0.001), with significantly higher rates of diabetes (P=0.004), ischemic heart
      disease (P=0.03), hypertension (P=0.001) and stroke disease (P=0.004).
      CONCLUSION: Colonoscopy performance in elderly Asians is similar to that in
      younger adults. However, the conscious sedation of these patients results in a
      higher rate of cardio-vascular complications.

PMID- 17532820
TI  - Activation of peroxisome proliferator-activated receptor gamma inhibits cell
      growth via apoptosis and arrest of the cell cycle in human colorectal cancer.
AB  - OBJECTIVE: To investigate the expression of peroxisome proliferator-activated
      receptors (PPAR)gamma and the effects of PPARgamma ligands on cells growth in
      colorectal cancer (CRC) cell line HT-29, and to explore whether the activation of
      PPARgamma by its selective ligand can induce apoptosis and the arrest of the cell
      cycle in these cells. METHODS: A CRC cell line, HT-29, was used in this study.
      PPARgamma mRNA and the protein expressions were measured by reverse transcriptase
      polymerase chain reaction and Western blot. The HT-29 cells were treated with two
      specific PPARgamma ligands: rosiglitazone and 15-d-PGJ2. The effects of PPARgamma
      activated by rosiglitazone and 15-d-PGJ2 on the anchorage-dependent and anchorage
      independent growth of the cells were assessed by methylthiazolyl terazolium (MTT)
      and soft agar colony assay, respectively. Apoptosis was measured by TUNEL
      staining and flow cytometry (FCM) assay by CaspSCREEN Flowcytometric Apoptosis
      Detection Kit (BioVision, Palo Alto, USA). Furthermore, the caspase-3 expression
      was determined by a immunocytochemical staining method before and after treatment
      with rosiglitazone and 15-d-PGJ2 for 48 h. The cell cycles were measured by flow
      cytometric analysis using propidium iodide (PI). RESULTS: PPARgamma mRNA and
      protein expressions were observed in the HT-29 cells. The MTT assay showed that
      treatment of these cells with 0, 0.1, 1 or 10 micromol/L PPARgamma activators
      rosiglitazone or 15-d-PGJ2 for 0, 24, 48 or 72 h resulted in the inhibition of
      anchorage-dependent cell growth in a dosage- and time-dependent way.
      Rosiglitazone treatment during cell growth resulted in the reduction of colony
      formation and the effects were not immediately reversible in the cell culture.
      TUNEL staining showed DNA fragmentation in positive cells after treatment with
      rosiglitazone and 15-d-PGJ2 for 48 h. In addition, FCM showed that the apoptosis
      rates were 14.8+/-0.8% and 28.5+/-1.3% or 15+/-0.7% and 40+/-1.2% after the cells
      were incubated with 10 micromol/L rosiglitazone or 15-d-PGJ2 for 24 h and 48 h,
      while the apoptosis rates of cells without treatment were 3.8+/-0.4% and 8.8+/
      0.4%, respectively. Consistent with these results, the positivity rates of
      caspase-3 expression in cells treated with rosiglitazone or 15-d-PGJ2 increased
      significantly when compared with the control group. To explore whether the
      regulation of the cell cycle was involved in the effect of PPARgamma ligands on
      cell growth, FCM using PI staining was assessed. The ratio of G0/G1 phase cells
      increased after incubated with 10 micromol/L rosiglitazone or 15-d-PGJ2 for 24 h
      and 48 h. CONCLUSIONS: Our results showed that PPARgamma was expressed in HT-29
      cells and PPARgamma activation could inhibit cell growth through inducing
      apoptosis and suppressing the cell cycle. PPARgamma may be considered as a new
      therapeutic target for colon cancer in humans.

PMID- 17532821
TI  - Targeting specificity and pharmacokinetics of asialoorosomucoid, a specific
      ligand for asialglycoprotein receptor on hepatocyte.
AB  - OBJECTIVE: To testify that the asialoorosomucoid (ASOR) prepared by us has liver
      targeting specificity and to investigate its pharmacokinetic characteristics.
      METHODS: The distribution of 125I-ASOR in vivo was determined by single photon
      emission computed tomography (SPECT) and immunohistochemical technique after 125I
      ASOR was injected into Sprague-Dawley (S-D) rats through their caudal veins. In
      vitro, different doses of pEGFP-N1 plasmid were transfected into both HepG2 cells
      and HT1080 cells with the use of ASOR-poly-L-lysine. At 24 and 48 h after
      transfection, the expression of green fluorescent protein (GFP) was determined
      under fluorescent microscope. Pharmacokinetic parameters were calculated
      according to two-compartment open system model with first-order kinetics.
      RESULTS: SPECT images showed that 125I-ASOR was located only in liver/stomach and
      root of caudal vein/bladder at 10 min after injection. The 125I-ASOR
      radioactivities of organs taken out from S-D rats were different at different
      times, and about 63% of 125I-ASOR was located in the liver at 10 min after
      injection. At 30 min after injection a peak of radioactivity was seen in stomach.
      The times of these two radioactivity peaks were different. Immunohistochemical
      study of liver frozen sections showed that ASOR was combined mainly with
      hepatocyte membrane, especially in areas with rich blood flow. In vitro study
      showed that ASOR targeted specifically cells with asialoglycoprotein receptor
      (ASGr). GFP expression was detected in HepG2 cells but not in HT1080 cells.
      Furthermore, the more quantity of pEGFP-N1 transfected and the longer expression
      time, the higher GFP expression level was in HepG2 cells. The 125I-ASOR
      pharmacokinetics equation for liver was Ct=662216e-3.362t+8896e-2343t. 125I-ASOR
      was excreted from liver slowly after an initial rapid decrease. The
      pharmacokinetic equation for stomach was Ct=-114815e-1.7t+1148153e-15t and the
      half-life of 125I-ASOR in stomach was 4.62 h. CONCLUSIONS: ASOR prepared by us
      could be an efficient gene transfer vector, ASOR was distributed mainly in the
      liver and stomach and had high targeting specificity to hepatocytes or hepatic
      originating cells.

PMID- 17532822
TI  - Effect of somatostatin on immune inflammatory response in patients with severe
      acute pancreatitis.
AB  - OBJECTIVE: Somatostatin regulates immune inflammatory response via apoptosis and
      adhesion of leukocytes in many diseases. This article reported a study that aimed
      to observe the mechanism and effect of somatostatin on the immune inflammatory
      response through apoptosis and adhesion of leukocytes in severe acute
      pancreatitis. METHODS: Thirty-eight patients with severe acute pancreatitis, that
      fulfilled the guidelines for the treatment of severe acute pancreatitis of China
      and Balthazar computed tomography severity index (>or=5) were enrolled
      consecutively. Nineteen of these patients received our routine treatment and 19
      received additional somatostatin. In all patients the expressions of CD4, CD8,
      CD95/CD95 ligand and CD18/CD62 ligand on leukocytes were determined by flow
      cytometry, both upon admission and on the fourth day. Thirty healthy volunteers
      constituted the normal healthy group. RESULTS: In the treatment group, CD4,
      CD4:CD8 ratio and CD62 ligand on leukocytes increased from 11.4+/-8.2, 0.47+/
      0.10 and 25.5+/-9.2 to 22.1+/-9.7, 0.68+/-0.11 and 36.2+/-11.7 (P<0.05)
      respectively, while CD95 ligand on both lymphocyte and polymorphonuclear cells
      increased from 0.65+/-0.21 and 0.76+/-0.29 to 1.18+/-0.32 and 1.58+/-0.43 after
      treatment with somatostatin (P<0.05). Furthermore, lactate dehydrogenase,
      aspartate aminotransferase, amylase, C reactive protein and acute physiology and
      chronic healthy evaluation (APACHE II) score in the treatment group reduced
      faster than those in the control group (P<0.05), though there was no difference
      in mortality (15.7% vs 5.3%) between the two patient groups (P>0.05). CONCLUSION:
      Somatostatin can modulate the immune inflammatory response and the severity of
      severe acute pancreatitis through apoptosis and adhesion of leukocytes, but this
      modulatory effect by itself is not strong enough to improve the final.

PMID- 17532823
TI  - Lymphadenopathy, elevated liver function tests and weight loss in a 68-year-old
      man.
AB  - A 68-year-old man presented to the hospital with fevers, weight loss,
      lymphadenopathy and abnormal liver-associated enzymes. After a thorough workup, a
      liver biopsy demonstrated histiocytes with phagocytosis of the lymphocytes and a
      positive immunostain for S-100. The diagnosis of Rosai-Dorfman disease was made.
      This case report will discuss the patient's presentation as well as the diagnosis
      and treatment of this rare, non-malignant disorder, which only rarely affects the
      liver.

PMID- 17532824
TI  - Consensus on chronic gastritis in China--Second National Consensus Meeting on
      Chronic Gastritis (14-16 September 2006 Shanghai, China).

PMID- 17532825
TI  - Assessment of variables affecting flow propagation velocity of the left ventricle
      in healthy children.
AB  - BACKGROUND: The purpose of the present study was to establish the normal values
      of flow propagation velocity (FPV) in healthy children and examine the variables
      that affect FPV in clinical situations. METHODS: Two hundred and thirty- five
      healthy children and adolescents were assessed (aged 0-22.6 years, mean age 7.4
      +/- 5.4 years; male, n = 142; female, n = 93). FPV was obtained from an apical
      four-chamber view and determined as the slope of aliasing velocity of early
      diastolic transmitral flow on the color M-mode using Aloka SSD-5500 with 5.0 MHz
      transducer. Aliasing velocity was set at 50-70% of the peak transmitral flow
      velocity. Peak transmitral flow velocities in early diastole (E) and during
      atrial contraction (A), and the ratio of early to late peak velocity (E/A) were
      obtained. Tei index was also measured for analysis of general left ventricular
      performance. Left ventricular mass index (LVMI) was obtained from conventional
      echo measurement. E, E/A, Tei index and LVMI were compared with FPV in healthy
      subjects. RESULTS: FPV obtained from all subjects ranged from 23.7 to 96.0 cm/s
      (61.3 +/- 13.6 cm/s). Normal value of FPV was less dependent on age, body size,
      heart rate and left ventricular dimension. In contrast, although there was no
      significant correlation between FPV and ejection fraction, statistically
      significant correlation was found between FPV, LVMI (P = 0.0008) and Tei index (P
      = 0.025). CONCLUSIONS: FPV is independent of age, body size and heart rate and is
      useful to assess left ventricular relaxation in children.

PMID- 17532826
TI  - Adjuvant effect of vitamin A on recurrent lower urinary tract infections.
AB  - BACKGROUND: The purpose of the present paper was to investigate the effects of
      vitamin A supplementation on recurrent lower urinary tract infections (RUTI).
      METHODS: Twenty-four patients with non-complicated RUTI were included in a
      placebo-controlled, double-blinded study. Twelve patients received a single dose
      of 200,000 IU vitamin A in addition to antimicrobial therapy. Patient and control
      groups (each containing 12 patients) were followed for up to 1 year and were
      evaluated for eradication and frequency of lower urinary tract infections (UTI).
      Serum levels of vitamin A and beta-carotene were determined periodically.
      RESULTS: During the first 6 months follow-up period the infection rate of the
      vitamin A-supplemented group reduced from 3.58 to 0.75 per 6 months, and in the
      subsequent 6 months the infection rate was 1.75 per 6 months. These values were
      calculated as 2.75, 2.83 and 2.66, respectively, in the placebo group.
      CONCLUSION: Vitamin A supplementation may have an adjuvant effect on the
      treatment of RUTI.

PMID- 17532827
TI  - Serum zinc levels in children with acute gastroenteritis.
AB  - BACKGROUND: The aim of the present study was to determine the serum zinc levels
      on admission and 7-10 days after clinical recovery from acute gastroenteritis of
      <8 days' duration. METHODS: This prospective study included 82 infants aged 2-24
      months who had no associated bacterial infection, chronic disease, prior
      antibiotic use, moderate or severe malnutrition or dysentery. Forty-one healthy
      children formed the control group. RESULTS: The mean serum zinc level on
      admission (Zn1) was 11.85 +/- 2.83 micromol/L and at 7-10 days after recovery
      (Zn2) was 10.92 +/- 2.17 micromol/L; mean serum zinc level of the control group
      was 11.81 +/- 3.45 micromol/L. Zn2 was significantly lower than Zn1, but there
      was no statistical difference between the mean of the control group and Zn1 and
      Zn2. When dehydrated patients were excluded from the patient group, Zn1 and Zn2
      did not differ. Although asymptomatic, 39% of the control group had low zinc.
      Serum zinc levels were not affected by sex, age, clinical characteristics of the
      patients or severity of gastroenteritis. CONCLUSION: Serum zinc levels of the
      patients admitted with acute gastroenteritis without any other disease and
      without moderate or severe malnutrition were not affected by disease state.
      Gastroenteritis did not further decrease serum zinc levels in patients with
      asymptomatic or subclinical zinc deficiency.

PMID- 17532828
TI  - In vitro production of bilirubin photoisomers by light irradiation using neoBLUE.
AB  - BACKGROUND: The light-emitting diode is used as one of the new light sources for
      phototherapy. NeoBLUE (Atom Medical, Tokyo, Japan) incorporates blue light
      emitting diodes for the treatment of neonatal hyperbilirubinemia. The authors
      compared the in vitro efficacy of neoBLUE with conventional phototherapy devices.
      METHODS: The three light devices used included neoBLUE and two conventional
      phototherapy devices with six blue-white (BW) or six green (GR) fluorescent
      tubes. A bilirubin/human serum albumin solution (15 mg/dL) in 200 x 300 mm
      elliptical bag was irradiated with each three light device. The average light
      intensity of neoBLUE, BW and GR was 22.5, 10.2 and 2.6 microW/cm(2) per nm,
      respectively, for the irradiated area. Bilirubin photoisomers and native
      bilirubin were measured by high-performance liquid chromatography. RESULTS: In
      neoBLUE, BW and GR, the respective production rate of cyclobilirubin was 6.0, 3.7
      and 3.9 x 10(-2) mg/dL/min, and the respective (4Z, 15E)-bilirubin/(4Z, 15Z)
      bilirubin ratio after irradiation was 0.44, 0.33 and 0.12; the (4Z, 15Z)
      bilirubin reduction rate at 20 min after irradiation was 60, 68 and 82%,
      respectively. The reduction rate of (4Z, 15Z)-bilirubin correlated with the (4Z,
      15E)-bilirubin/(4Z, 15Z)-bilirubin ratio. CONCLUSION: Phototherapy using the
      neoBLUE under high level may be clinically more effective than therapy using the
      conventional light source from the results of the production rate of
      cyclobilirubin.

PMID- 17532829
TI  - Montelukast decreased exhaled nitric oxide in children with perennial allergic
      rhinitis.
AB  - BACKGROUND: Measurement of exhaled nitric oxide (eNO) is a simple and noninvasive
      method for assessment of inflammatory airway diseases. eNO is elevated in
      adolescent patients with perennial allergic rhinitis and related to bronchial
      hyperresponsiveness. The aim of this study was to investigate whether oral
      loratadine, montelukast, nasal budesonide or nasal sodium cromoglycate could
      reduce airway inflammation as indicated by decrease of eNO in children with
      perennial allergic rhinitis as demonstrated by eNO levels. METHODS: A randomized
      and investigator-blinded study was conducted in a hospital-based outpatient
      clinic. Children with perennial allergic rhinitis were divided into four groups
      and treated by loratadine, loratadine with nasal sodium cromoglycate, loratadine
      with oral montelukast, and loratadine with nasal budesonide, respectively.
      Allergic rhinitis scores, eNO and peak expiratory flow were measured before and
      2, 4, 6 and 8 weeks after treatment. RESULTS: Results showed that eNO in children
      with perennial allergic rhinitis was reduced by nasal budesonide and oral
      montelukast within 2 weeks (24.56 +/- 14.42 vs 18.42 +/- 12.48, P < 0.001, in
      budesonide group; 27.81 +/- 13.4 vs 19.09 +/- 10.45, P < 0.001, in montelukast
      group), but not in the loratadine and cromoglycate groups. In contrast,
      loratadine or sodium cromoglycate also did not decrease eNO levels although they
      could decrease the symptom scores. CONCLUSIONS: It was concluded that four common
      treatment modalities could effectively release symptom scores, but decrease of
      airway inflammation as determined by decrease of eNO might be only achieved by
      nasal budesonide and montelukast, but not nasal sodium cromoglycate and
      loratadine. Children with perennial allergic rhinitis with high eNO levels may
      require oral montelukast or nasal budesonide treatment to prevent airway
      hyperresponsiveness.

PMID- 17532830
TI  - Effects of Spascupreel versus hyoscine butylbromide for gastrointestinal cramps
      in children.
AB  - BACKGROUND: Gastrointestinal spasms and cramps are common in children as well as
      in adults. Alternative medical practices such as chiropractice and homeopathy are
      becoming increasingly popular in Europe and the USA. The effectiveness and
      tolerability of the homeopathic preparation Spascupreel was compared with that of
      hyoscine butylbromide treatment in children <12 years of age. METHODS: An
      observational cohort study in 204 children <12 years was conducted over a 1 week
      treatment period. The efficacy of the respective therapies were evaluated on the
      effect on severity of spasms and clinical symptoms (pain/cramps, sleep
      disturbances, distress, eating or drinking difficulties and frequent crying).
      Compliance was evaluated on a four-point scale from 'very good' to 'low'.
      Evaluation was done by the practitioner based on information given by the patient
      or minder. RESULTS: The analysis showed comparative improvements with the
      homeopathic preparation and hyoscine butylbromide therapy on severity of spasms,
      pain/cramps, sleep disturbances, eating or drinking difficulties, and frequent
      crying, all as evaluated by the practitioner. Both treatments were very well
      tolerated. CONCLUSIONS: For patients opting for a homeopathic therapy,
      Spascupreel seems to be an effective and well tolerated alternative to
      conventional therapies in children suffering from gastrointestinal spasms.

PMID- 17532831
TI  - Side-effects of long-term prostaglandin E(1) treatment in neonates.
AB  - BACKGROUND: In some neonates suffering from ductus arteriosus dependent
      congenital heart defect, a Prostaglandin E(1) (PGE1) therapy longer than 2 weeks
      may be needed. However, PGE1 analogue compounds may produce several adverse
      effects. METHODS: The authors retrospectively analyzed the data of nine patients
      who underwent a PGE1 treatment lasting longer than 14 days. RESULTS: The
      leukocyte count of the patients remained high throughout the treatment period,
      and the proportion of neutrophils was over 50%. Transient feeding difficulty and
      abdominal distension, and possible signs of gastric-outlet obstruction, were
      observed in two cases. In the case of three patients, cortical hyperostosis
      developed after different cumulative doses (1584, 3384 and 4320 microg).
      Significant correlations were found between the doses of PGE1 and serum K(+)
      levels (r=-0.770, P < 0.05) and between the blood standard bicarbonate levels and
      PGE1 doses (r= 0.889, P < 0.01). Bartter syndrome-like condition developed in
      those three patients who received the largest cumulative doses. CONCLUSIONS:
      Fluid-electrolyte parameters must be controlled frequently in the case of each
      patient treated with PGE1 for longer than 2 weeks. Although the dose, the length
      of the therapy and individual susceptibility may be equally important, fluid
      electrolyte disturbances and the development of pseudo-Bartter syndrome seem to
      be more dose-dependent than cortical hyperostosis.

PMID- 17532832
TI  - Intraventricular hemorrhage in preterm newborns: risk factors and results from a
      University Hospital in Istanbul, 8 years after.
AB  - BACKGROUND: In this prospective study, the authors aimed to show intraventricular
      hemorrhage (IVH) incidence of premature newborns in the Neonatal Intensive Care
      Unit of Cerrahpasa Faculty of Medicine, Istanbul, Turkey, and its risk factors,
      and they tried to compare these results with those they reported 8 years ago.
      METHODS: A total of 103 premature newborns, hospitalized between August 2003 and
      January 2005 with a gestational age equal or less than 33 weeks, were included in
      this study. IVH rates and changes in the incidences of risk factors were compared
      with those that had been reported between January 1995 and January 1997. RESULTS:
      Mean birthweight of this population was 1400 +/- 380 g (min, 550 g; max, 2000 g)
      and gestational age 30.3 +/- 2.1 weeks (min, 25 weeks; max, 33 weeks). IVH was
      diagnosed in 13 (13%) of them. IVH rates were 37, 10 and 5% for birthweight
      groups 501-1000, 1001-1500 and 1501-200 g, respectively. Statistically
      significant risk factors were found to be birthweight, gestational age, clinical
      risk index for babies score >5, mechanical ventilation, sepsis and hypotension.
      Maternal corticosteroid administration was found to be significantly protective.
      IVH rates and incidences of risk factors in this study were decreased compared to
      those reported 8 years ago. CONCLUSIONS: In developing countries, where well
      equipped Neonatal Intensive Care Units are limited, prevention of prematurity,
      better prenatal care and maternal corticosteroid administration become essential
      points for the prevention of IVH and its neurological consequences.

PMID- 17532833
TI  - Renal replacement therapies in pediatric intensive care patients: experiences of
      one center in Turkey.
AB  - BACKGROUND: Despite constant improvements in caring for critically ill neonates
      and infants with congenital cardiac disease, sepsis, bone marrow and solid organ
      transplantation, acute renal failure (ARF) is an important problem in these
      children. ARF, severe fluid overload and inborn errors of metabolism are some of
      the indications for acute dialysis in infants and children. METHODS: The authors
      had retrospectively evaluated the medical records of Pediatric Intensive Care
      Unit, Ankara University School of Medicine, Ankara, Turkey patients who had
      required acute renal replacement therapy between the dates of January 2002 to
      February 2005. RESULTS: Medical records of 332 patients were reviewed. Acute
      renal replacement therapy was performed in 21 patients (6.3%; mean age, 9.6 +/-
      7.4 years). Dialysis modalities were peritoneal dialysis in 15 patients (71.4%;
      mean age, 3.9 +/- 5.6 years) and hemodialysis in six patients (28.6%; mean age,
      12.1 +/- 3.2 years). A total of 90% of patients had severe systemic disease
      leading to ARF. A total of 95% of patients had multiple organ dysfunction
      syndrome. The most common cause of ARF was refractory shock. At the beginning of
      renal replacement therapy, 10 patients were anuric, nine patients had volume
      overload, seven patients had decompensated metabolic acidosis and nine patients
      had hypotension. The average dialysis period was 4.7 +/- 6.4 days. Mortality rate
      was 66.7%. Eight patients recovered from ARF and chronic renal failure had
      developed in one patient. CONCLUSION: In the Pediatric Intensive Care Unit, ARF
      is frequently seen together with multiple organ dysfunction syndrome and the
      mortality rate is high. Both peritoneal dialysis and hemodialysis are important
      renal replacement treatment modalities in patients with ARF. The age and
      hemodynamic status of the patients are important when choosing treatment
      modality; generally peritoneal dialysis is preferred in infants and toddler,
      while hemodialysis is preferred in older children.

PMID- 17532834
TI  - Low-dose methylprednisolone pulse therapy in Chinese children with steroid
      resistant focal segmental glomerulosclerosis.
AB  - BACKGROUND: Focal segmental glomerulosclerosis (FSGS) is a primary glomerular
      disease that usually progresses to renal failure. Although high-dose pulse
      methylprednisolone therapy (PMT) has been shown to be effective in the treatment
      of steroid-resistant FSGS, adverse effects have caused parents to hesitate in
      approving the treatment. The aim of this study is to investigate whether low-dose
      PMT based protocol for treatment of young children with steroid resistant FSGS
      would effectively induce remission of proteinuria and prevent the progression of
      renal insufficiency. METHODS: This is a retrospective study. The authors treated
      eight children with steroid-resistant FSGS with intravenous methylprednisolone
      pulse 10 mg/kg per day for three consecutive days weekly for 8 weeks. Partial
      responders were treated with the addition of chlorambucil or cyclosporine (CsA)
      and four fortnightly and eight monthly pulses of high-dose PMT (30 mg/kg per
      day). RESULTS: Of the eight patients, six attained complete remission initially.
      The median urinary protein excretion in 24 h decreased from 4.25 to 0.39 g
      following 8 weeks of low dose (P = 0.012). Marked decrease in urinary protein
      creatinine ratio was noted soon after treatment (P = 0.012). There was a
      significant increase in serum albumin level after treatment compared to the
      pretreatment condition (median, 3.35 vs 4.1 mg/dL, P = 0.018). Five of the eight
      patients remained in complete remission, and one of the eight patients relapsed
      during follow up. Relapse responded to repeated treatments of PMT and
      cyclosporine. The two patients with partial remission initially progressed to
      renal insufficiency in one patient and end-stage renal disease in the other
      patient. CONCLUSIONS: Low-dose PMT caused a significant decrease in the
      proteinuria of Chinese children with steroid-resistant FSGS with a low frequency
      of intolerance.

PMID- 17532835
TI  - Clinical and epidemiologic features of invasive group A streptococcal infections
      in children.
AB  - BACKGROUND: Invasive group A streptococcal infection (IGASI) is a disease of
      public health importance. The clinical epidemiology of IGASI in children has not
      been studied extensively in Florida, USA. The objective of this study was to
      describe the clinical and epidemiologic features of children hospitalized for
      IGASI in Florida, USA, during a 4-year period. METHODS: Data from a previous
      retrospective cohort study of IGASI were analyzed. The study subjects were
      children and adults who had been hospitalized throughout Florida for IGASI
      between 1996 and 2000 and reported to the Florida Department of Health. A total
      of 25 patients who were 0 to 17 years of age were identified and included in the
      current pediatric case series. RESULTS: The median age at the time of admission
      was 4 years (range, 0.05-17 years). A total of 14 cases (56%) were boys. In
      total, 18 of the pediatric patients had group A streptococcal bacteremia and
      three children were diagnosed with group A streptococcal necrotizing fasciitis.
      Various antibiotic regimens were used. A total of 33% (7/21) of the patients
      received clindamycin during their hospital stay. Data on mortality were available
      for 23 pediatric IGASI cases and 205 adult IGASI cases. The mortality rate was
      4.4% in children as compared to 19.5% in adults (Fisher's two-sided P = 0.087).
      CONCLUSIONS: The low case-fatality in children was consistent with other
      pediatric series of IGASI.

PMID- 17532836
TI  - Clinical spectrum of tuberculous pleural effusion in children.
AB  - BACKGROUND: The aim of this study was to describe the clinical characteristics
      and potentially diagnostic specimens of pediatric patients with tuberculous
      pleural effusion (TPE) to make a prompt diagnosis. METHODS: Children who had TPE
      from September 1997 to December 2003 were retrospectively reviewed at a tertiary
      pediatric facility in northern Taiwan. RESULTS: There were seven boys and six
      girls and their ages ranged from 10 to 17 years (average, 14.6 years).
      Tuberculosis contact history was identified in only six patients (46%). Fever
      (12/92%), cough (9/69%) and malaise (6/46%) were the most common symptoms. Normal
      leukocyte count was found in 12 patients (92%). Chest radiograph review showed
      unilateral pleural effusion in 12 patients (92%) but parenchymal involvement was
      found in nine patients (69%). Most of the pleural fluid analysis showed a
      lymphocytic exudative effusion (5/6). The acid-fast bacilli (AFB) stain of
      sputum, gastric washing, and pleural aspirate was positive in six of 11 (55%),
      two of seven (29%), and one of five (20%) patients, respectively. Culture of
      sputum, gastric washing, and pleural aspirate yielded Mycobacterium tuberculosis
      in four of 11 (36%), two of seven (29%), and two of five (40%) patients,
      respectively. A total of 6 to 9 months of multiple-drug therapy for tuberculosis
      was successful without sequale. CONCLUSIONS: Tuberculous pleural effusion usually
      presents as an acute illness and should always be considered in the differential
      diagnosis for older children and adolescents with pneumonia. A normal leukocyte
      count with a lymphocytic exudative effusion may provide a clue to the correct
      diagnosis of TPE. Diagnostic specimen of sputum seems more effective and
      sensitive in childhood TPE, especially those having pulmonary involvement.

PMID- 17532837
TI  - Mycoplasma pneumonia: clinical and radiographic features in 39 children.
AB  - BACKGROUND: The purpose of the present paper was to evaluate the clinical and
      chest radiographic features of pediatric patients with serologically proven
      Mycoplasma pneumoniae pneumonia (mycoplasma pneumonia). METHODS: The clinical
      records and chest radiographs of 39 consecutive patients (19 male, 20 female; age
      3-13 years) with serologically positive IgG and IgM mycoplasma pneumonia were
      reviewed. RESULTS: More than 90% of patients presented with fever and cough and
      48% of patients had leukocyte count >10,000/mm(3). A C-reactive protein (CRP)
      level >0.375 mg/dL was noted in 28 patients (72%). Chest radiographs displayed
      four different patterns: (i) peribronchial and perivascular interstitial
      infiltrates (n= 19, 49%); (ii) airspace consolidations (n= 15, 38%); (iii)
      reticulonodular opacification (n= 3, 8%); and (iv) nodular or mass-like
      opacification (n= 2, 5%). Bilateral peribronchial perivascular interstitial
      infiltrations in central and middle lung zones were frequently seen (n= 19, 49%).
      Other radiological features were bilateral lesions in 51% of patients, pleural
      effusion in 23%, and hilar lymphadenopathy in 13%. Means of duration for
      treatment response and hospitalization were 2.5 and 5 days, respectively.
      CONCLUSION: There are various radiological features of mycoplasma pneumonia in
      children. Bilateral peribronchial and perivascular interstitial infiltrates were
      most frequently seen in the present patients.

PMID- 17532838
TI  - Seroepidemiology of hepatitis B virus infection among children in Mongolia:
      results of a nationwide survey.
AB  - BACKGROUND: Because Mongolia is one of the highly endemic countries for hepatitis
      B virus (HBV) infection in the world, hepatitis B (HB) vaccine was introduced
      into the National Expanded Program on Immunization in 1991. However, relatively
      few data are available concerning HBV infection among children born after the
      start of the program, so far. The aim of the present paper was to describe the
      seroepidemiology of HBV infection among primary school children using
      representative national data. METHODS: In 2004, a nationwide school-based cross
      sectional serosurvey was carried out throughout Mongolia, covering both urban and
      rural areas. Serum samples were tested for hepatitis B surface antigen (HBsAg),
      antibody to hepatitis B core antigen (anti-HBc) and hepatitis B e antigen (HBeAg)
      as well as for liver enzymes. RESULTS: A total of 1145 children aged 7-12 years
      were studied, which represents nearly 2% of the second grade population of
      elementary schools in Mongolia. The overall prevalence of HBsAg and anti-HBc was
      5.2% (95% confidence interval [CI]: 3.9-6.5%) and 15.6% (95%CI: 13.5-17.7%),
      respectively. Among HBsAg-positive children 67.8% (95%CI: 55.9-79.7%) were also
      positive for HBeAg. The prevalence of chronic HBV infection increased by age and
      was significantly higher among children from rural areas compared to those from
      urban areas (7.7% vs 3.0%; P < 0.001). In the multivariate logistic regression
      analysis, rural residence (odds ratio [OR]: 2.57; 95%CI: 1.45-4.58), male sex
      (OR: 1.9; 95%CI: 1.08-3.26) and age (OR: 1.5; 95%CI: 1.10-2.05) were independent
      demographic predictors for chronic HBV infection. CONCLUSIONS: The prevalence of
      chronic HBV infection has been decreasing in the Mongolian young generation, most
      likely due to infant HB vaccination. However, significant rural-urban differences
      in the prevalence of HBV infection were found that demand further investigation
      to estimate the potential causes.

PMID- 17532839
TI  - Prader-Willi syndrome in Taiwan.
AB  - BACKGROUND: Prader-Willi syndrome (PWS) is a congenital disorder caused by absent
      expression of paternal genes in 15q11-13 affecting multiple systems. The
      information concerning the clinical features of this genetic disorder is
      incomplete in Taiwan. METHODS: A retrospective analysis was carried out of 70 PWS
      patients (39 male, 31 females; age range, 1 month-22 years) seen in four major
      medical centers in Taiwan from January 1980 through June 2005. All cases were
      confirmed by methylation-specific polymerase chain reaction. The molecular
      characteristics, birth history, clinical presentation and laboratory studies were
      analyzed. RESULTS: Complete genetic analysis was performed in 52 of the 70
      patients with PWS. The abnormalities found included deletions in 45 (87%),
      maternal uniparental disomy (UPD) in five (10%), and a probable imprinting center
      deletion or an imprinting defect in two (4%). The average weight of the patients
      at birth was 2588 +/- 540 g. Bone age delay of >2 years and growth hormone (GH)
      deficiency were noted in 11/40 (28%) and 12/20 (60%), respectively. In the 18 in
      whom both bone age and GH were assessed, abnormalities of both were found in two
      (11%). In 2000, Taiwan instituted the Rare Diseases and Orphan Drugs Act and
      mandated a three-phase screening protocol for PWS. Of the 41 patients diagnosed
      with PWS before 2000, only four (10%) were diagnosed before the age of 3 months;
      in the 29 patients diagnosed after 2000, in 15 (52%) the syndrome was confirmed
      before 3 months of age (P < 0.001). CONCLUSIONS: The present finding is in
      contrast to that of most previous reports that indicated a higher incidence of
      UPD in PWS. It is unclear whether this discrepancy in the incidence of UPD arises
      from under-diagnosis or because of ethnic differences, a question worthy of
      further study. The three-phase screening protocol has generated notable
      improvement in the early diagnosis of PWS in Taiwan.

PMID- 17532840
TI  - Clinical characteristics and survival of trisomy 13 in a medical center in
      Taiwan, 1985-2004.
AB  - BACKGROUND: This study investigated the survival and natural history of trisomy
      13 in a series of patients, comparing the management and outcome before and after
      the implementation of Taiwan's National Health Insurance program (NHI). METHODS:
      A total of 28 cases of trisomy 13 seen at Mackay Memorial Hospital, Taipei,
      Taiwan, from 1985 to 2004 were retrospectively reviewed. Survival and management
      before (12 cases) and after (16 cases) the implementation of National Health
      Insurance were compared, and structural defects, imaging findings, and
      cytogenetic results were analyzed. The cases that were diagnosed prenatally, and
      finally terminated, were excluded from this study. The diagnosis of trisomy 13
      was based on the postnatal chromosome analysis. RESULTS: All patients except one
      with trisomy 13 translocation died in their first year because of severe
      malformations of the cardiovascular or central nervous system. The median
      survival was 9 days. After implementation of National Health Insurance, survival
      with trisomy 13 was significantly longer than before (P < 0.05). The three most
      common structural defects were abnormal auricular helices or low-set ears (89%),
      cryptorchidism and abnormal scrotum of male (73%) and cleft lip and/or palate
      (71%). Using echocardiography, the most commonly detected heart defects were
      patent ductus arteriosus (68%), ventricular septal defect (50%) and atrial septal
      defect (50%), and eight cases (36%) had complex congenital heart defects. The
      most common brain lesion was lenticulostriate vasculopathy (22%), followed by
      holoprosencephaly (17%), brain edema (13%) and subependymal cyst (13%).
      CONCLUSIONS: Early diagnosis and the survival patterns from the data collected
      should be used to inform parents and health-care professionals to assist in
      decision making. Although most patients with trisomy 13 die within the first
      weeks after birth, it is important to recognize that a few may survive the first
      year. When counseling families, the long-term survival prospects of trisomy 13
      patients should be included.

PMID- 17532841
TI  - Low dose of rectal thiopental sodium for pediatric sedation in spiral computed
      tomography study.
AB  - BACKGROUND: The aim of this study was to determine the effectiveness of reduced
      new dose in rectal sedation by thiopental sodium for computed tomography (CT)
      diagnostic imaging. METHODS: A total of 90 children (mean age, 24.21 month +/-
      13.63 [standard deviation]) underwent spiral CT study after rectal administration
      of thiopental sodium injection solution. The new dose ranged from 15 to 25 mg/kg
      with a total dose of 350 mg. The percentage of success and adverse reaction were
      evaluated. RESULTS: Sedation was successful in 98% of infants and children with
      an average time of 8.04 min +/- 6.87 (standard deviation). One of the cases found
      desaturation, two experienced vomiting, 14 found rectal defecation, and two
      experienced hyperactivity. No prolonged sedation was observed. CONCLUSION: Rectal
      administration of thiopental sodium for pediatric CT imaging is safe and
      effective even for hyperextend position by new reduced dose of the drug. This
      procedure could be easily done in the CT department under supervision of the
      radiologist.

PMID- 17532842
TI  - Usefulness of DNA analysis of tuberculosis with ruptured lymphadenitis in a
      bacille Calmette-Guerin-vaccinated infant.

PMID- 17532843
TI  - Cerebral edema in a child with diabetic ketoacidosis before initial treatment.

PMID- 17532844
TI  - Dilated cardiomyopathy due to nutritional vitamin D deficiency rickets.

PMID- 17532845
TI  - Esophageal perforation in an abandoned newborn.

PMID- 17532846
TI  - Toxic shock syndrome toxin-1-mediated exanthematous disease in a burned infant.

PMID- 17532847
TI  - Atopic dermatitis and transient hypogammaglobulinemia of infancy improved
      simultaneously.

PMID- 17532848
TI  - Duodenal appearance of giardiasis in a child with selective immunoglobulin A
      deficiency.

PMID- 17532850
TI  - Teratoid Wilms' tumor in a child.

PMID- 17532849
TI  - Acute conjunctivitis caused by Actinobacillus ureae.

PMID- 17532851
TI  - Hazards of early BCG vaccination: BCGitis in a patient with chronic granulomatous
      disease.

PMID- 17532852
TI  - Elastin expression and elastic fibre width in the anterior vaginal wall of
      postmenopausal women with and without prolapse.
AB  - OBJECTIVES: To compare elastin expression and elastic fibre width in the anterior
      vaginal wall of postmenopausal women with and with no bladder prolapse. PATIENTS
      AND METHODS: Full-thickness specimens were obtained from the upper lateral
      anterior vaginal wall of women having a large cystocele repaired (stage III or
      IV; prolapse group, 33) and the same location in patients with no prolapse having
      radical cystectomy (control group, 10). The percentage of elastin-positive tissue
      and elastic fibre width were measured by immunohistochemistry on 6 microm thick
      tissue sections from 10 random field readings per sample using image analysis
      software. The examiner was unaware of sample identity and the patients' clinical
      history. RESULTS: The age was comparable between the control and prolapse groups
      (median 70.5 years), and the parity, vaginal deliveries, hormone replacement use,
      cigarette smokers and body mass index were no different between the groups.
      Immunohistochemical staining and morphometric analysis indicated that elastin
      expression in the prolapse group was 10.6%, vs 14.4% in the control group (P =
      0.049). The median width of elastic fibres was 0.9 microm in the prolapse and 1.8
      microm in the control groups (P < 0.001). Elastin expression and elastic fibre
      width appeared to be stable with increasing age in the prolapse group.
      CONCLUSIONS: In this case-control study investigating elastin changes in
      postmenopausal women with prolapse, the elastin expression and fibre width were
      significantly lower in the vaginal wall of patients with a large cystocele than
      in controls of a similar age.

PMID- 17532853
TI  - Introducing levels of evidence to publications in urology.

PMID- 17532854
TI  - The importance of the chronic kidney disease guidelines in urology.

PMID- 17532855
TI  - Elective management of transitional cell carcinoma of the distal ureter: can
      kidney-sparing surgery be advised?
AB  - OBJECTIVE: To determine the long-term oncological outcome of patients with
      primary transitional cell carcinoma (TCC) of the distal ureter electively treated
      with either kidney-sparing surgery (KSS) or radical nephroureterectomy (RNU) in a
      retrospective, non-randomized, single-centre study. PATIENTS AND METHODS: Of 43
      consecutive patients with a primary solitary distal ureter TCC, 19 had KSS,
      consisting of distal ureter resection with bladder cuff excision and ureter
      reimplantation, and 24 had RNU with bladder cuff excision. RESULTS: The median
      (range) age at surgery was 69 (31-86) years for the KSS group and 73 (59-87)
      years for the RNU group, patients in the latter having worse hydronephrotic
      kidneys. The median (range) follow-up was 58 (3-260) months. A recurrent bladder
      tumour was diagnosed after a median of 15 months in five of the 19 patients
      treated by KSS and after a median of 5.5 months in eight of the 24 treated by
      RNU. Five of the 19 patients treated by KSS and six of the 24 treated by RNU died
      from metastatic disease despite chemotherapy. Recurrence-free, cancer-specific
      and overall survival were comparable in the two groups. In two patients (11%)
      treated by KSS an ipsilateral upper urinary tract TCC recurred after 42 and 105
      months, respectively. CONCLUSION: Treatment by distal ureteric resection is
      feasible in patients with primary TCC of the distal ureter. The long-term
      oncological outcome seems to be comparable with that of patients treated by RNU.
      Furthermore, kidney preservation is advantageous if adjuvant or salvage
      chemotherapy is required.

PMID- 17532856
TI  - Low nuclear ErbB3 predicts biochemical recurrence in patients with prostate
      cancer.
AB  - OBJECTIVE: To further evaluate the association between the cytoplasmic or nuclear
      localization of ErbB3 with biochemical recurrence (BCR) in patients with prostate
      cancer and positive surgical margins, as there is a greater risk of BCR for such
      patients after radical prostatectomy (RP). PATIENTS AND METHODS: We recently
      noted that ErbB3, which is normally associated with the plasma membrane, can
      translocate to the nucleus, an event which appears to be associated with disease
      progression. We evaluated ErbB3 expression and localization using
      immunohistochemistry on tissue samples from 55 patients with positive surgical
      margins after RP; 30 of these 55 (55%) had BCR after 3 years of follow-up. The
      relationship between ErbB3 nuclear localization and BCR (prostate-specific
      antigen, PSA, >0.3 ng/mL) after RP was analysed by Kaplan-Meier survival analysis
      and Cox regression models. RESULTS: The BCR-free survival probability at 3 years
      was 0.65 and 0.35 for positive and negative nuclear ErbB3, respectively (Kaplan
      Meier, P = 0.029). Patients negative for nuclear ErbB3 had a 2.47-fold increase
      in BCR frequency in a univariate Cox model (P = 0.008) and it remained an
      independent prognostic marker when combined with clinical prognostic variables in
      a multivariate model (P = 0.023). CONCLUSION: Low nuclear localization of ErbB3
      is a predictor of BCR in patients with prostate cancer and positive surgical
      margins after RP.

PMID- 17532857
TI  - Psychosocial barriers to active surveillance for the management of early prostate
      cancer and a strategy for increased acceptance.
AB  - OBJECTIVES: To review the psychosocial needs of men undergoing active
      surveillance (AS, the monitoring of early prostate cancer, with curative
      intervention only if the disease significantly progresses) for prostate cancer,
      and barriers to its uptake. METHODS: The introduction of screening for prostate
      specific antigen (PSA) has led to more men diagnosed with early and nonlife
      threatening forms of prostate cancer; about half of men diagnosed as a result of
      PSA testing have cancers that would never cause symptoms if left untreated and
      yet up to 90% of such men receive curative therapy, then living with the toxicity
      of treatment but with no benefit. Thus AS is increasingly being promoted, but if
      such a strategy is to succeed, the psychosocial barriers that discourage men from
      adopting AS must be addressed. We reviewed and assessed reports on this topic,
      published in English since 1994. RESULTS: There is relatively little research on
      AS, as most published reports refer to watchful waiting (which is a palliative
      management approach). Men with prostate cancer generally have lower levels of
      psychological disturbance than for other cancers, but the psychosocial issues
      identified include anxiety in response to no intervention, uncertainty related to
      loss of control, and lack of patient education and support, particularly around
      the time of initial treatment planning. Approaches that were identified to
      improve uptake of AS include increased education and improved communication,
      interventions to reduce anxiety and uncertainty, and the empowerment of patients
      by the development of a sense of control and meaning. Physicians attitudes are
      influential and the education of physicians about AS as an appropriate option is
      to be encouraged. Peer-support groups were also identified as being of particular
      value. CONCLUSIONS: There are several strategies that should be developed if AS
      is to become more widely adopted. Increased education and good communication can
      alleviate anxiety and uncertainty, as can interventions for cognitive re-framing.
      Inviting patients to become active participants in their management might enhance
      the patients' sense of control, and the involvement of peer-support groups might
      be beneficial.

PMID- 17532858
TI  - Repeated botulinum-A toxin injections in the treatment of myelodysplastic
      children and patients with spinal cord injuries with neurogenic bladder
      dysfunction.
AB  - OBJECTIVES: To examine the effects of repeated detrusor injections of botulinum-A
      toxin (BTX) for possible changes in bladder function, muscular structure of the
      detrusor, increase in BTX tolerance (tachyphylaxis) and side-effects, as BTX is a
      new treatment alternative for patients with a neurogenic bladder condition that
      is difficult to treat and refractory to anticholinergic medication. PATIENTS AND
      METHODS: Between 2000 and 2005, 19 patients with myelodysplasia (MDP) and 25
      spinal cord-injured (SCI) patients were treated with repeated suburothelial BTX
      injections (Dysport, Ipsen-Pharma, Ettlingen, Germany) or injections into the
      intramural detrusor. The follow-up was > or = 3 years (range 3-5, median 4.5).
      RESULTS: Detrusor compliance, bladder capacity, and detrusor pressure at maximum
      filling improved significantly (P < 0.001) compared to baseline after each BTX
      injection. There was prolonged efficacy of each BTX administration and all
      repeated injections in the paediatric and adult patients with neurogenic bladder
      dysfunction over a median follow-up of 4.5 years. There was no evidence for drug
      tolerance or changes in the morphological appearance of the bladder. Safety was
      good: no complications were associated with the injection procedure itself. Early
      in the treatment programme, three patients who received a dose of 1000 units
      Dysport showed systemic side-effects and generalized muscle weakness. These
      resolved without intervention and did not recur after reducing the adult dose to
      750 units (paediatric dose 20 units/kg, not >400 units), which seems to be the
      optimum for good efficacy with an adequate safety margin. CONCLUSION: BTX
      injection is a safe and effective treatment for neurogenic detrusor
      hyperreflexia. Repeat treatments are as effective as the first: there was no
      indication of a lack of efficacy due to tachyphylaxis, antibody formation, or
      fibrosis of the detrusor muscle in this sample.

PMID- 17532859
TI  - Altered 'active' antireflux mechanism in primary vesico-ureteric reflux: a
      morphological and manometric study.
AB  - OBJECTIVE: To immunolocate c-kit-positive interstitial cells of Cajal (ICCs,
      known to be responsible for pacemaker activity in human ureters, coordinating
      ureteric motility) in the intramural ureter of patients with different grades of
      vesico-ureteric reflux (VUR), to assess the ureteric histology and correlate
      these findings with manometric patterns. PATIENTS AND METHODS: The VU junction
      (VUJ) represents the boundary between the low-pressure of the upper and high
      pressure of the lower urinary tract, protecting the upper tract from VUR using
      active and passive antireflux mechanisms. The contraction of the longitudinal
      muscle coat of the VUJ possibly functions as an 'active' antireflux system, but
      previous manometric findings on refluxing ureteric units (RUs) have shown altered
      patterns. In all, 32 RU ends were stained using both picro-Mallory and Sirius Red
      techniques; in a parallel immunohistochemical procedure, using mast cell tryptase
      and CD117 antibodies (to identify ICCs), they were compared with eight control
      ureteric ends. Ureteric manometry of the VUJ was also done during ureteric
      reimplantation. RESULTS: The histochemical and immunohistochemical results in the
      RUs showed a replacement of the altered smooth muscle fascicles by collagenous
      stroma and significant loss of ICCs in RU ends, both correlated with the grade of
      VUR. Ureteric manometry showed significant impairment of basal and maximum
      pressure in RUs, correlated, respectively, with histological lesions and loss of
      ICCs. CONCLUSION: Deficiency of the longitudinal muscle coat probably leads to
      dysfunction and insufficiency of the ostial valve mechanism, with subsequent
      impairment of the active valve mechanism. Histological, histochemical and
      immunohistochemical changes support the alterations of ureteric peristalsis in
      RUs.

PMID- 17532860
TI  - Modular organization in the reductive evolution of protein-protein interaction
      networks.
AB  - BACKGROUND: The variation in the sizes of the genomes of distinct life forms
      remains somewhat puzzling. The organization of proteins into domains and the
      different mechanisms that regulate gene expression are two factors that
      potentially increase the capacity of genomes to create more complex systems. High
      throughput protein interaction data now make it possible to examine the
      additional complexity generated by the way that protein interactions are
      organized. RESULTS: We have studied the reduction in genome size of Buchnera
      compared to its close relative Escherichia coli. In this well defined
      evolutionary scenario, we found that among all the properties of the protein
      interaction networks, it is the organization of networks into modules that seems
      to be directly related to the evolutionary process of genome reduction.
      CONCLUSION: In Buchnera, the apparently non-random reduction of the modular
      structure of the networks and the retention of essential characteristics of the
      interaction network indicate that the roles of proteins within the interaction
      network are important in the reductive process.

PMID- 17532861
TI  - Chickens get their place in the sun.
AB  - A report on the International Chick Meeting 'The Chick as a Model Organism:
      Genes, Development and Function', Barcelona, Spain, 11-14 April 2007.

PMID- 17532862
TI  - Short-term appetite control in response to a 6-week exercise programme in
      sedentary volunteers.
AB  - Previous cross-sectional studies have shown that sedentary males, unlike their
      active counterparts, are unable to compensate for previous energy intake (EI).
      The present study therefore investigated the effects of a 6-week moderate
      exercise programme (4 times per week, 65-75 % maximal heart rate) on appetite
      regulation in healthy sedentary volunteers using a longitudinal design. EI at a
      buffet meal 60 min after high-energy (HEP; 607 kcal) and low-energy (LEP; 246
      kcal) preloads, together with 24 h cumulative EI, were measured in twenty-five
      healthy volunteers (eleven men; mean age 30 (SD 12) years, mean BMI 22.7 (SD 2.3)
      kg/m2), at baseline and after the exercise intervention. Subjective hunger and
      fullness were assessed throughout using visual analogue scales. ANOVA showed a
      significant preload x exercise interaction on 24 h cumulative EI, supporting an
      improvement in appetite control over this time period with the exercise
      programme. There was a trend towards improvement in energy compensation over the
      same period (8.9 (SD 118.5) % v. 79.5 (SD 146..4) %; P = 0.056). No preload x
      exercise interaction was observed for buffet EI. Secondary analysis, however,
      showed that although buffet EI after the two preloads was not significantly
      different at baseline, buffet EI after the HEP was significantly lower than after
      the LEP following the exercise intervention. The improvement in short-term
      appetite control with exercise was not explained by changes in subjective hunger
      or satiety. This longitudinal study supports the original cross-sectional
      findings and suggests that exercise may have a significant impact on short-term
      appetite control by leading to a more sensitive eating behaviour in response to
      previous EI. Further studies are needed to clarify the mechanisms involved.

PMID- 17532863
TI  - Oestrogen receptor alpha is required for biochanin A-induced apolipoprotein A-1
      mRNA expression in HepG2 cells.
AB  - Epidemiological studies have indicated that soya consumption may produce a better
      plasma lipid profile. The effect may be attributed to the phyto-oestrogens in
      soya. The red clover (Trifolium pratense) isoflavone biochanin A has a chemical
      structure similar to those phyto-oestrogens found in soya beans, and is marketed
      as a nutraceutical for alleviating postmenopausal symptoms. In the present study
      we investigated the effect of biochanin A on the mRNA expression of ApoA-1 in the
      hepatic cell line HepG2. Real-time PCR revealed that biochanin A increased ApoA-1
      mRNA abundance in cells expressing oestrogen receptor (ER) alpha. Without ERalpha
      transfection, biochanin A had no effect on mRNA abundance. In order to study the
      transcriptional control, a fragment of the 5'-flanking region of the ApoA-1 gene
      was amplified and inserted in a firefly luciferase reporter plasmid. The reporter
      assay indicated that the transactivation of the ApoA-1 promoter was induced by
      biochanin A in HepG2 cells transfected with the ERalpha expression plasmid. This
      induction was reduced by the anti-oestrogen ICI 182,780, whereas the inhibitors
      of protein kinase (PK) C, PKA, or mitogen-activated kinase (ERK) had no
      suppressive effect. The present study illustrated that biochanin A might up
      regulate hepatic apoA-1 mRNA expression through an ER-dependent pathway.

PMID- 17532864
TI  - Naturalistic follow-up of co-morbid substance use in schizophrenia: the West
      London first-episode study.
AB  - BACKGROUND: The impact of co-morbid substance use in first-episode schizophrenia
      has not been fully explored. METHOD: This naturalistic follow-up of a cohort of
      152 people with first-episode schizophrenia examined substance use and clinical
      outcome in terms of symptoms and social and neuropsychological function. RESULTS:
      Data were collected on 85 (56%) of the patient cohort after a median period of 14
      months. Over the follow-up period, the proportion of smokers rose from 60% at
      baseline to 64%. While 30% reported lifetime problem drinking of alcohol at
      baseline, only 15% had problem drinking at follow-up. Furthermore, while at
      baseline 63% reported lifetime cannabis use and 32% were currently using the
      drug, by the follow-up assessment the latter figure had fallen to 18.5%. At
      follow-up, persistent substance users had significantly more severe positive and
      depressive symptoms and greater overall severity of illness. A report of no
      lifetime substance use at baseline was associated with greater improvement in
      spatial working memory (SWM) at follow-up. CONCLUSIONS: Past substance use may
      impede recovery of SWM performance in people with schizophrenia in the year or so
      following first presentation to psychiatric services. The prevalence of substance
      use other than tobacco tends to diminish over this period, in the absence of
      specific interventions. Persistent substance use in first-episode schizophrenia
      is associated with more severe positive and depressive symptoms but not negative
      symptoms, and should be a target for specific treatment intervention.

PMID- 17532865
TI  - A comparative study of methods for diagnosis of obesity in an urban mixed-race
      population in Minas Gerais, Brazil.
AB  - BACKGROUND: Obesity is defined as an excess of total body fat and may be assessed
      by different methods. The objective of the present study was to establish the
      discriminatory power of anthropometric data in determining obesity. METHODS: The
      subjects comprised 685 individuals, aged 20-79 years, sampled from a population
      based survey. The following indicators were used: body mass index (BMI), waist
      circumference (WC) and total body fat percentage estimated with both Siri's
      equation (%BF Siri) and foot-to-foot bioelectrical impedance analysis (%BF BIA).
      Sensitivity and specificity of different cut-off points for each method were
      determined using %BF BIA as reference. RESULTS: Of 685 participants, 57.6% were
      aged >/= 40 years, 69.9% were women and 72.6% self-referred themselves as non
      white. To classify obesity based on sex and age among women aged 0.05).
      Classifying according to skin colour did not change cut-off points in any
      indicator. CONCLUSION: BMI and WC better discriminate obesity among women and men
      aged >/= 40 years from a mixed-race population.

PMID- 17532866
TI  - Circulating salicylic acid is related to fruit and vegetable consumption in
      healthy subjects.
AB  - Salicylic acid (SA) is a natural phenolic compound known as the active principle
      of aspirin. Its presence in vegetal sources suggests that fruit and vegetable
      (FV) consumption could produce measurable SA serum concentrations in human
      subjects not taking aspirin. The aim of this study was to investigate the
      relationship between FV intake and circulating SA in healthy subjects. Thirty
      eight volunteers (twenty-two males and sixteen females) were recruited from an
      Italian university campus. They recorded their food intake for 7 d to evaluate
      dietary consumption and, in particular, FV intake; fasting blood samples were
      taken on the morning of the eighth day to measure SA serum concentration, using a
      sensitive stable isotope dilution and GC-MS method. Median SA serum concentration
      was 0.124 mumol/l (range 0.028-0.295). Circulating SA was significantly related
      to FV consumption, both to the mean daily intake (r2 0.13, P = 0.03) and to the
      last day intake (r2 0.16, P = 0.01). The subjects in the highest FV intake
      quartile in the preceding day (>4.75 servings) had significantly higher SA
      concentrations than in the lowest quartile ( < 2.3 servings) (median
      concentrations 0.188 and 0.112 mumol/l, respectively; P = 0.04). This study
      proved that, after overnight fast, human subjects not taking aspirin display
      circulating SA in amounts related to the FV consumption. It is therefore possible
      that the beneficial effects of regular FV consumption in man could also depend on
      low chronic SA exposure.

PMID- 17532867
TI  - Dietary patterns in infancy: the importance of maternal and family influences on
      feeding practice.
AB  - It is not known what constitutes an optimal diet in infancy. There are relatively
      few studies of weaning practice in the UK, and there is a need for prospective
      data on the effects of infant diet and nutrition on health in later life. We
      describe the dietary patterns, defined using principal components analysis of FFQ
      data, of 1434 infants aged 6 and 12 months, born between 1999 and 2003. The two
      most important dietary patterns identified at 6 and 12 months were very similar.
      The first pattern was characterised by high consumption of fruit, vegetables and
      home-prepared foods ('infant guidelines' pattern). The second pattern was
      characterised by high consumption of bread, savoury snacks, biscuits and chips
      ('adult foods' pattern). Dietary pattern scores were correlated at 6 and 12
      months (r 0.46 'infant guidelines'; r 0.45 'adult foods'). These patterns, which
      reflect wide variations in weaning practice, are associated with maternal and
      family characteristics. A key influence on the infant diet is the quality of the
      maternal diet. Women who comply with dietary recommendations, and who have high
      intakes of fruit and vegetables, wholemeal bread and rice and pasta, are more
      likely to have infants who have comparable diets--with high 'infant guidelines'
      pattern scores. Conversely, women whose own diets are characterised by high
      intakes of chips, white bread, crisps and sweets are more likely to have infants
      who have high 'adult foods' pattern scores. The effects of these patterns on
      growth and development, and on long-term outcomes need to be investigated.

PMID- 17532869
TI  - [Work-related cancer still underreported].

PMID- 17532868
TI  - Energy, macronutrient and fatty acid intake of French elderly community dwellers
      and association with socio-demographic characteristics: data from the Bordeaux
      sample of the Three-City Study.
AB  - Few data are available regarding dietary habits of the elderly, in particular
      about fatty acid consumption, whereas these are major risk or protective factors
      of several age-related diseases. The aim of the present study was to characterise
      the dietary intake of a French elderly population in terms of energy,
      macronutrients and fatty acids based on their socio-demographic characteristics.
      The study population (age range 67.7-94.9 years) consisted of 1786 subjects from
      Bordeaux (France), included in the Three-City cohort. Dietary assessment was
      performed by a 24 h recall, allowing the estimation of energy, protein,
      carbohydrate, total fat, SFA, MUFA and PUFA intakes. Socio-demographic
      characteristics (age, sex, marital status, educational level and income),
      practice of sports and BMI were registered. Total energy intake (EI) was lower in
      women and in older participants ( > or = 85 years) but higher in single subjects.
      Higher EI was associated with higher income, but not with educational level. Mean
      contribution of macronutrients to EI (protein 18%, carbohydrate 46% and total fat
      31%) was higher in women than men, except for alcohol. The oldest individuals
      consumed less protein and more mono- and disaccharides. Excess saturated fat
      intake (43% of total fat), associated with a relative deficit in MUFA consumption
      (36% of total fat), was observed. The mean 18:2n-6:18:3n-3 ratio was 9.9 and
      decreased with higher educational level. The present results suggest that being
      female, older age, being widowed and low income level could be considered as risk
      factors of inadequate dietary intake.

PMID- 17532871
TI  - [Disturbance in processing auditory impulses from the ears: auditory processing
      disorder].
AB  - Over the last decade evidence on the existence of auditory processing disorder
      (APD) has increased. Therefore, it is now time to deal with the phenomenon in
      daily clinical work. This article gives information about APD, especially about
      problems with the definition of APD, diagnosing APD and the treatment.

PMID- 17532870
TI  - [Do antipsychotic drugs during pregnancy affect the unborn baby?].
AB  - Treatment with antipsychotic drugs has resulted in an increased number of well
      treated patients who--like healthy women--wish to become pregnant. Studies of the
      effect of these drugs on the unborn child are few, and this puts the treating
      physician in a dilemma of choosing the right treatment. The present study reviews
      the existing literature on the ten most sold antipsychotic drugs in Denmark
      focusing on study design, number of exposed women and risks for the unborn child.
      Only few studies of the antipsychotic drugs in question are available, and these
      studies have not shown any significant risk of teratogenicity. Use of
      antipsychotic drugs should, however, be avoided during the first 3 months of
      pregnancy. If this is not possible, it is recommended to use the lowest dose
      possible for as short a period as possible. In addition, an obstetrician should
      follow the pregnant woman very closely, and the pregnant woman should give birth
      in a department with close contact to neonatal expertise.

PMID- 17532872
TI  - [Plaster of Paris splinting/bandaging of lower leg and ankle].

PMID- 17532873
TI  - [Recommendation for identical growth curves in Denmark].
AB  - Growth monitoring is essential for the evaluation of health in children. Growth
      and final height have changed over time, the secular trend, and therefore updated
      growth curves are important. In this article the growth curves in use in Denmark
      are reviewed. In 2003 two different growth curves with older reference
      populations were used for growth evaluation after the neonatal period, and five
      different growth curves were in use for neonatal growth evaluation. To make
      growth evaluation more homogeneous we recommend one updated Scandinavian growth
      curve for child growth monitoring in Denmark.

PMID- 17532874
TI  - [Surgical versus endoscopic treatment of bile duct stones].

PMID- 17532875
TI  - [Registration of selected cases of occupational cancer (1994-2002) with the
      Danish National Board of Industrial Injuries].
AB  - INTRODUCTION: Persons in Denmark afflicted by an occupational disease are offered
      economical compensation and it is the responsibility of the physician to register
      such cases with the Danish National Board on Industrial Injuries. However, the
      number of cancers reported to the Board is lower than expected. We evaluated the
      causes of underreporting for two types of cancer with a major occupational
      background. MATERIALS AND METHODS: Cases of pleural mesothelioma and
      adenocarcinoma of the sinonasal cavities diagnosed between 1994 and 2002 were
      drawn from the Danish Cancer Registry. Patients were searched for in the files of
      the National Board of Industrial Injuries. For patients not registered,
      information on employment history since 1964 and job title was collected from the
      Danish Supplementary Pension Fund and the Central Population Register, and the
      likelihood of occupational exposure to asbestos and wood dust was evaluated.
      RESULTS: 695 individuals were registered with pleural mesothelioma and 108 with
      adenocarcinoma of the sinonasal cavities in the Cancer Registry. Of these, 381
      (55%) patients with mesothelioma and 44 (41%) patients with adenocarcinoma were
      also registered with the National Board of Industrial Injuries. Among the latter,
      91% and 87%, respectively were judged by the Board to be occupationally induced.
      For 3 out of 4 cases not registered with the Board register-based occupational
      information was available. This information indicated exposure to asbestos by 60%
      of the men and 3% of the women; the equivalent figures for adenocarcinoma and
      wood dust were 32% and 0%, respectively. CONCLUSION: We observed a substantial
      underreporting of pleural mesothelioma and adenocarcinoma of the sinonasal
      cavities with the National Board of Industrial Injuries. The underreporting
      seemed to be unchanged since the 1980s. We propose that all cases of mesothelioma
      and all cases of cancer of the sinonasal cavities not registered with the Board
      are referred to a department for industrial medicine for etiological evaluation.

PMID- 17532876
TI  - [A 50-year register follow-up of 112 patients with a classic diagnosis of
      neurosis].
AB  - INTRODUCTION: The study is a register follow-up on a group of patients with a
      diagnosis of neurosis according to the Danish psychiatric/psychoanalytical
      tradition. The study group consists of the 'hospital material' used by the late
      Erling Jacobsen, M.D., in his doctoral thesis of 1965. MATERIALS AND METHODS: The
      cohort consists of 112 patients (30 males (26.8%) and 82 females (73.2%))
      hospitalized in the years 1952 to 1957. These patients were suffering from
      anxiety neuroses, obsessive-compulsive states or hysterical neuroses. In an early
      phase of the study, a systematic review of all records was made in order to re
      diagnose the patients according to DSM-III. The results presented in the study
      are therefore mainly based on the DSM-III categories. RESULTS: The original
      categorization of patients into anxiety neurosis, obsessive-compulsive states or
      hysterical neurosis did not have any prognostic significance as to readmission or
      death. DSM-III diagnoses result in a similar picture. During follow-up a total of
      67 patients died. There was a weak but insignificant excess mortality of 1.16 for
      men and 1.14 for women. Death by suicide was significantly increased for both
      sexes. Most suicides occurred relatively soon after discharge. Of all the 112
      patients, 81.2% remained in the original diagnostic main category, while 14.3%
      received a psychosis diagnosis. CONCLUSION: The neurosis diagnosis according to
      Danish psychiatric tradition appears rather stable. On the other side, a minor
      fraction of patients were later diagnosed as being psychotic. The opinion that
      'real' neurotics could not be later re-diagnosed as non-neurotics has therefore
      not been confirmed.

PMID- 17532877
TI  - [Psychosocial problems and needs among cancer patients].
AB  - INTRODUCTION: Cancer can have a serious impact on patient well-being and quality
      of life. The international literature reports a higher prevalence of psychosocial
      problems among cancer patients; primarily problems associated with difficulties
      in the family, duties in the household, work and leisure, sexuality and finances.
      The prevalence of these problems among Danish cancer patients is still unknown.
      MATERIALS AND METHODS: A questionnaire assessing psychosocial problems and needs
      was mailed out to all patients who had been at the Department of Oncology, Aarhus
      Hospital in week 35, 2004. A total of 71%, i.e. 515 patients (34% men and 66%
      women) in active treatment and control returned the questionnaire. RESULTS: High
      levels of emotional distress were reported by 39% of the patients. High levels of
      distress were primarily related to problems with worries about their spouses,
      household duties, financial problems and experiences of insufficient
      collaboration between health care and social services. Between 19% and 25% of the
      patients required further help to handle emotional problems, legal and financial
      problems and practical problems in the home. CONCLUSION: A considerable
      proportion of oncology patients experience significant levels of distress. This
      group of distressed patients also report unmet needs for psychosocial support.

PMID- 17532878
TI  - [Validation of methods to identify known diabetes on the basis of health
      registers].
AB  - INTRODUCTION: In 2003 the government introduced a national diabetes plan. One of
      the recommendations was to establish a national diabetes database targeted at
      monitoring the prevalence of diabetes and quality of diabetes care. The aim of
      this study is to validate a national algorithm for identification of known
      diabetes and compare the results with the results from the use of a regional
      algorithm. MATERIALS AND METHODS: Patients with diabetes residing in Aarhus
      County on 31 December 2003 were identified by data from The National Patient
      Registry, The National Health Insurance Service Registry, the prescription
      database and the laboratory database in the county. RESULTS: This study
      identified a total of 8,802 patients with a diagnosis of diabetes which was
      confirmed by the patients' general practitioners (GP). This corresponds to a
      prevalence of 2.32% (95% CI: 2.27%2.37%). The national algorithm found 86% of
      this diabetes population while the regional algorithm found 96%. The sensitivity
      was increased to 91% by supplementing with information of dispensed prescriptions
      for anti-diabetics in the national algorithm. The positive predictive value was
      89% for the national algorithm as well as for the regional algorithm. CONCLUSION:
      The national algorithm may be used as a tool for establishing a national diabetes
      database. Despite a higher sensitivity, the regional algorithm cannot currently
      be recommended at a national level as it depends on the collection of person
      related data which are not available nationally at the present time.

PMID- 17532879
TI  - [Pneumomediastinum as a sign of anastomotic leakage].
AB  - Anastomotic defect after colorectal surgery usually presents with clinical and
      biochemical signs and is confirmed by radiological studies. We report a rare case
      of anastomotic defect in the form of pneumomediastinum. The patient had no
      clinical signs of leakage, and no defect was found during acute laparotomy,
      performed because of wound dehiscence after the primary operation.
      Pneumomediastinum was found by chest radiography. Radiological examination of the
      colon with water-soluble contrast confirmed the leakage, and laparotomy revealed
      an anastomotic defect retroperitoneally.

PMID- 17532880
TI  - [Necrotizing fasciitis after arthroscopic synovectomy of an infected prepatellar
      bursa].
AB  - Necrotizing fasciitis (NF) is a life-threatening soft tissue infection in
      superficial and deep fascias. NF is most often caused by mixed aerobic and
      anaerobic bacteria. The treatment is early and aggressive surgical debridement,
      antibiotics and hyperbaric oxygen. In this case description, a nearly 60-year-old
      man developed NF after arthroscopic synovectomy of an infected prepatellar bursa.
      We stress the point that the endoscopic technique itself might be responsible for
      the spreading of bacteria to the fascias. This is a subject for further
      investigation.

PMID- 17532881
TI  - Real-time multichannel imaging framework for endoscopy, catheters, and fixed
      geometry intraoperative systems.
AB  - To address the need for a clinically applicable intravital optical imaging
      system, we developed a new hardware and software framework. We demonstrate its
      utility by applying it to an endoscope-based white light and fluorescent imaging
      system. The capabilities include acquisition and visualization algorithms that
      perform registration, segmentation, and histogram-based autoexposure of two
      imaging channels (full-spectrum white light and near-infrared fluorescence), all
      in real time. Data are processed and saved as 12-bit files, matching the
      standards of clinical imaging. Dynamic range is further improved by the
      evaluation of flux as a quantitative parameter. The above features are
      demonstrated in a series of in vitro experiments, and the in vivo application is
      shown with the visualization of fluorescent-labeled vasculature of a mouse
      peritoneum. The approach may be applied to diverse systems, including handheld
      devices, fixed geometry intraoperative devices, catheter-based imaging, and
      multimodal systems.

PMID- 17532883
TI  - In vitro and in vivo evaluation of Alexa Fluor 680-bombesin[7-14]NH2 peptide
      conjugate, a high-affinity fluorescent probe with high selectivity for the
      gastrin-releasing peptide receptor.
AB  - Gastrin-releasing peptide (GRP) receptors are overexpressed on several types of
      human cancer cells, including breast, prostate, small cell lung, and pancreatic
      cancers. Bombesin (BBN), a 14-amino acid peptide that is an analogue of human
      GRP, binds to GRP receptors with very high affinity and specificity. The aim of
      this study was to develop a new fluorescent probe based on BBN having high tumor
      uptake and optimal pharmacokinetics for specific targeting and optical imaging of
      human breast cancer tissue. In this study, solid-phase peptide synthesis was used
      to produce H(2)N-glycylglycylglycine-BBN[7-14]NH(2) peptide with the following
      general sequence: H(2)N-G-G-G-Q-W-A-V-G-H-L-M-(NH(2)). This conjugate was
      purified by reversed-phase high-performance liquid chromatography and
      characterized by electrospray-ionization mass spectra. The fluorescent probe
      Alexa Fluor 680-G-G-G-BBN[7-14]NH(2) conjugate was prepared by reaction of Alexa
      Fluor 680 succinimidyl ester to H(2)N-G-G-G-BBN[7-14]NH(2) in dimethylformamide
      (DMF). In vitro competitive binding assays, using (125)I-Tyr(4)-BBN as the
      radiolabeling gold standard, demonstrated an inhibitory concentration 50% value
      of 7.7 +/- 1.4 nM in human T-47D breast cancer cells. Confocal fluorescence
      microscopy images of Alexa Fluor 680-G-G-G-BBN[7-14]NH(2) in human T-47D breast
      cancer cells indicated specific uptake, internalization, and receptor blocking of
      the fluorescent bioprobe in vitro. In vivo investigations in SCID mice bearing
      xenografted T-47D breast cancer lesions demonstrated the ability of this new
      conjugate to specifically target tumor tissue with high selectivity and affinity.

PMID- 17532884
TI  - Multitracer positron emission tomographic imaging of exogenous gene expression
      mediated by a universal herpes simplex virus 1 amplicon vector.
AB  - To develop efficient and safe gene therapy approaches, the herpes simplex virus
      type 1 thymidine kinase gene (HSV-1-tk) has been shown to function as a marker
      gene for the direct noninvasive in vivo localization of thymidine kinase (TK)
      expression by positron emission tomography (PET) using radiolabeled nucleoside
      analogues as specific TK substrates. Moreover, the gene encoding dopamine type 2
      receptor (d2r) could be used as a PET marker gene using specific radiolabeled
      receptor binding compounds. Here we describe the quantitative colocalization of
      d2r and HSV-1-tk gene expression mediated from a universal HSV-1 amplicon vector
      in a subcutaneous human Gli36dEGFR glioma model by PET. The HSV-1 amplicon vector
      was constructed using a bicistronic gene cassette to contain (1) the d2r80A
      mutant, which is able to bind its ligand racloprid but unable to activate
      downstream signal transduction pathways, and (2) the tk39 mutant with enhanced
      enzymatic activity toward guanosine analogues fused to the green fluorescent
      protein gene (tk39gfp) serving as a marker gene in cell culture. After infection
      of human Gli36dEGFR glioma cells with the HSV-d2r80AIREStk39gfp (HSV-DITG)
      amplicon vector in cell culture, D2 receptor expression and its targeting to the
      cell surface were determined by Western blotting and immunolabeling. Vector
      application in vivo served for quantitative colocalization of d2r80A- and tk39gfp
      derived PET signals employing the specific D2 receptor binding compound
      [(11)C]racloprid and the specific TK39 substrate 9-(4-[(18)F]fluoro-3
      hydroxymethylbutyl)guanine. Our results demonstrate that for the range of gene
      expression studied in vivo, both enzymatic and receptor binding assays give
      comparable quantitative information on the level of vector-mediated gene
      expression in vivo. The d2r80A in combination with a specific binding compound
      passing the intact blood-brain barrier might be an alternative marker gene for
      the noninvasive assessment of vector-mediated gene expression in the brain using
      PET.

PMID- 17532882
TI  - Forebrain ischemia-reperfusion simulating cardiac arrest in mice induces edema
      and DNA fragmentation in the brain.
AB  - Brain injury affects one-third of persons who survive after heart attack, even
      with restoration of spontaneous circulation by cardiopulmonary resuscitation. We
      studied brain injury resulting from transient bilateral carotid artery occlusion
      (BCAO) and reperfusion by simulating heart attack and restoration of circulation,
      respectively, in live C57Black6 mice. This model is known to induce neuronal
      death in the hippocampus, striatum, and cortex. We report the appearance of edema
      after transient BCAO of 60 minutes and 1 day of reperfusion. Hyperintensity in
      diffusion-weighted magnetic resonance imaging (MRI) was detectable in the
      striatum, thalamus, and cortex but not in the hippocampus. To determine whether
      damage to the hippocampus can be detected in live animals, we infused a T(2)
      susceptibility magnetic resonance contrast agent (superparamagnetic iron oxide
      nanoparticles [SPIONs]) that was linked to single-stranded deoxyribonucleic acid
      (DNA) complementary in sequence to c-fos messenger ribonucleic acid (SPION-cfos);
      we acquired in vivo T(2)*-weighted MRI 3 days later. SPION retention was measured
      as T(2)* (milliseconds) signal reduction or R(2)* value (s(-1)) elevation. We
      found that animals treated with 60-minute BCAO and 7-day reperfusion exhibited
      significantly less SPION retention in the hippocampus and cortex than sham
      operated animals. These findings suggest that brain injury induced by cardiac
      arrest can be detected in live animals.

PMID- 17532885
TI  - In vivo optical imaging of acute myeloid leukemia by green fluorescent protein:
      time-domain autofluorescence decoupling, fluorophore quantification, and
      localization.
AB  - Human xenografts of acute myeloid leukemia (AML) in nonobese diabetic/severe
      combined immunodeficient (NOD/SCID) mice result in disease states of diffuse,
      nonpalpable tissue infiltrates exhibiting a variable disease course, with some
      animals not developing a disease phenotype. Thus, disease staging and, more
      critically, quantification of preclinical therapeutic effect in these models are
      particularly difficult. In this study, we present the generation of a green
      fluorescent protein (GFP)-labeled human leukemic cell line, NB4, and validate the
      potential of a time-domain imager fitted with a 470 nm picosecond pulsed laser
      diode to decouple GFP fluorescence from autofluorescence on the basis of
      fluorescence lifetime and thus determine the depth and relative concentration of
      GFP inclusions in phantoms of homogeneous and heterogeneous optical properties.
      Subsequently, we developed an optical imageable human xenograft model of NB4-GFP
      AML and illustrate early disease detection, depth discrimination of leukemic
      infiltrates, and longitudinal monitoring of disease course employing time-domain
      optical imaging. We conclude that early disease detection through use of time
      domain imaging in this initially slowly progressing AML xenograft model permits
      accurate disease staging and should aid in future preclinical development of
      therapeutics for AML.

PMID- 17532887
TI  - Color transformation and fluorescence of Prussian blue-positive cells:
      implications for histologic verification of cells labeled with superparamagnetic
      iron oxide nanoparticles.
AB  - Superparamagnetic iron oxide (SPIO) nanoparticles, either modified or in
      combination with other macromolecules, are being used for magnetic labeling of
      stem cells and other cells to monitor cell trafficking by magnetic resonance
      imaging (MRI) in experimental models. The correlation of histology to MRI depends
      on the ability to detect SPIO-labeled cells using Prussian blue (PB) stain and
      fluorescent tags to cell surface markers. Exposure of PB-positive sections to
      ultraviolet light at a wavelength of 365 nm commonly used fluorescence microscopy
      can result in color transformation of PB-positive material from blue to brown.
      Although the PB color transformation is primarily an artifact that may occur
      during fluorescence microscopy, the transformation can be manipulated using
      imaging process software for the detection of low levels of iron labeled cells in
      tissues samples.

PMID- 17532886
TI  - Nonlinear optical imaging to evaluate the impact of obesity on mammary gland and
      tumor stroma.
AB  - Obesity is an established risk factor for breast cancer incidence and mortality.
      However, the mechanism that links obesity to tumorigenesis is not well
      understood. Here we combined nonlinear optical imaging technologies with an early
      onset diet-induced obesity breast cancer animal model to evaluate the impact of
      obesity on the composition of mammary gland and tumor stroma. Using coherent anti
      Stokes Raman scattering and second harmonic generation on the same platform, we
      simultaneously imaged mammary adipocytes, blood capillaries, collagen fibrils,
      and tumor cells without any labeling. We observed that obesity increases the size
      of lipid droplets of adipocytes in mammary gland and collagen content in mammary
      tumor stroma, respectively. Such impacts of obesity on mammary gland and tumor
      stroma could not be analyzed using standard two-dimensional histologic
      evaluation. Given the importance of mammary stroma to the growth and migration of
      tumor cells, our observation provides the first imaging evidence that supports
      the relationship between obesity and breast cancer risk.

PMID- 17532888
TI  - Short- and long-term effects of an intensive inpatient vision rehabilitation
      program.
AB  - OBJECTIVE: To assess the effects of a visual rehabilitation program on visually
      impaired subjects' visual ability and ability to perform activities. DESIGN:
      Prospective observational study. SETTING: Telephone interviews of respondents in
      their homes the week before admission to the rehabilitation center and 3 months
      and 1 year after discharge from the rehabilitation center. PARTICIPANTS: A total
      of 178 consecutive patients from the Hines Blind Rehabilitation Center
      participated in development of the 48-item Veterans Affairs Low Vision Visual
      Functioning Questionnaire (VA LV VFQ-48). Data were analyzed for 95 who
      participated in all 3 administrations of the questionnaire. INTERVENTION:
      Comprehensive blind rehabilitation program (mean hospital admission, 40 d). MAIN
      OUTCOME MEASURE: The self-report ratings of patients' difficulty performing 48
      activities on the VA LV VFQ-48. RESULTS: The increase in visual ability +/-
      standard deviation of .981+/-.482 logits (equivalent to an 8-line improvement in
      visual acuity on an Early Treatment of Diabetic Retinopathy Study chart) at 3
      months postrehabilitation decreased to .682+/-.485 logits (equivalent to a loss
      of 2.5 lines of visual acuity on the same chart) 1 year postrehabilitation. The
      effect sizes measured at 3 months (2.035) and 1 year (1.495) indicate large
      treatment effects corresponding to statistically significant differences for the
      increase in visual ability at 3 months and 1 year postrehabilitation (paired 2
      tailed t tests, P<.001) relative to pretreatment measures. The difference in
      visual abilities measured at 3 months and 1 year posttreatment also is
      statistically significant (P<.001). CONCLUSIONS: Treatment effects decreased over
      the 12-month follow-up period. However, the group of patients whose data were
      analyzed was still statistically and clinically significantly better at their 1
      year follow-up than before beginning treatment.

PMID- 17532889
TI  - Youth and young adults with cerebral palsy: their use of physician and hospital
      services.
AB  - OBJECTIVES: To examine patterns of health care utilization among youth and young
      adults who have cerebral palsy (CP) and to provide information to guide the
      development of health services for adults who have CP. DESIGN: This study
      analyzed health insurance data for outpatient physician visits and hospital
      admissions for a 4-year period. SETTING: Six children's treatment centers in
      Ontario, Canada. PARTICIPANTS: The sample included 587 youth and 477 adults with
      CP identified from health records. Youths were 13 to 17 years of age, and adults
      were 23 to 32 years of age at the end of the data range. INTERVENTIONS: Not
      applicable. MAIN OUTCOME MEASURES: We computed the annual rates of outpatient
      physician visits and hospitalizations per 1000 persons and compared these with
      rates for the general population. RESULTS: Annual rates of outpatient physician
      visits were 6052 for youth and 6404 for adults with CP, 2.2 times and 1.9 times
      higher, respectively, than rates for age-matched peers (P<.01). Specialists
      provided 28.4% of youth visits but only 18.8% of adult visits. Annual hospital
      admission rates were 180 for youth and 98 for adults with CP, 4.3 times and 10.6
      times higher, respectively, than rates for age-matched peers (P<.01).
      CONCLUSIONS: It appears that youth and adults with CP continue to have complex
      care needs and rely heavily on the health care system. Comprehensive services are
      essential to support their health as they move into youth and adulthood. However,
      there appear to be gaps in the adult health care system, such as limited access
      to specialist physicians.

PMID- 17532890
TI  - Effects of graduated compression stockings on cardiovascular and metabolic
      responses to exercise and exercise recovery in persons with spinal cord injury.
AB  - OBJECTIVE: To investigate whether reporting blood redistribution by means of
      graduated elastic stockings affects exercise and postexercise responses in people
      with spinal cord injury (SCI). DESIGN: Crossover trial. SETTING: Physical
      medicine and rehabilitation department in France. PARTICIPANTS: Fourteen men with
      traumatic SCI, grouped according to their level of injury. INTERVENTIONS:
      Subjects performed 2 maximal wheelchair exercise tests 1 week apart, in random
      order and under a counter-balanced design. One test was done with and the other
      without graduated elastic stockings (21 mmHg). MAIN OUTCOME MEASURES: Blood
      lactate, blood pressure, heart rate, maximal power output, and oxygen consumption
      (Vo2). RESULTS: Postexercise venous lactate concentration was reduced in SCI
      subjects with lesion levels below T6 while wearing graduated elastic stockings
      during both exercise and recovery (10.9+/-3.9 mmol/L vs 12.5+/-4.6 mmol/L,
      P<.05). There were no significant differences in submaximal and maximal values
      (heart rate, Vo2, power output) between subjects tested with and without
      graduated elastic stockings. CONCLUSIONS: Wearing elastic stockings affects
      postexercise responses by decreasing lactate concentration in well-trained, low
      level paraplegic patients after a maximal exercise. The relatively low pressure
      generated by the stockings may not, however, influence the venous system enough
      to produce improved performance and cardiovascular responses.

PMID- 17532891
TI  - Effect of sensory-amplitude electric stimulation on motor recovery and gait
      kinematics after stroke: a randomized controlled study.
AB  - OBJECTIVE: To evaluate the effects of sensory-amplitude electric stimulation
      (SES) of the paretic leg on motor recovery and gait kinematics of patients with
      stroke. DESIGN: Randomized, controlled, double-blind study. SETTING:
      Rehabilitation ward and gait laboratory of a university hospital. PARTICIPANTS: A
      total of 30 consecutive inpatients with stroke (mean age, 63.2 y), all within 6
      months poststroke and without volitional ankle dorsiflexion were studied.
      INTERVENTION: Both the SES group (n=15) and the placebo group (n=15) participated
      in a conventional stroke rehabilitation program 5 days a week for 4 weeks. The
      SES group also received 30 minutes of SES to the paretic leg without muscle
      contraction 5 days a week for 4 weeks. MAIN OUTCOME MEASURES: Brunnstrom stages
      of motor recovery and time-distance and kinematic characteristics of gait.
      RESULTS: Brunnstrom stages improved significantly in both groups (P<.05). In
      total, 58% of the SES group and 56% of the placebo group gained voluntary ankle
      dorsiflexion. The between-group difference of percentage change was not
      significant (P>.05). Gait kinematics was improved in both groups, but the between
      group difference was not significant. CONCLUSIONS: In our patients with stroke,
      SES of the paretic leg was not superior to placebo in terms of lower-extremity
      motor recovery and gait kinematics.

PMID- 17532892
TI  - Dimensionality and construct validity of the Fugl-Meyer Assessment of the upper
      extremity.
AB  - OBJECTIVE: To investigate the dimensionality and construct validity of the Fugl
      Meyer Assessment of the upper extremity by using Rasch analysis. DESIGN:
      Secondary analysis of pooled data from 2 existing datasets: a randomized
      therapeutic exercise clinical trial and a cohort longitudinal study of stroke
      recovery. SETTING: University research center. PARTICIPANTS: A total of 512
      subjects, ages 69.8+/-11.1 years, who were 0 to 145 days poststroke.
      INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Dimensionality was examined
      with principal components analysis and Rasch item-fit statistics. The Rasch
      derived item hierarchy was examined for consistency with the expected course of
      poststroke upper-extremity recovery suggested by the reflex-hierarchical
      conceptual model underlying the assessment. RESULTS: Factor loadings and item
      infit statistics suggested that the 3 reflex items were empirically disconnected
      from other assessment items. The reflex items were removed. The modified 30-item
      assessment showed a unidimensional structure. The Rasch-item-difficulty order was
      not consistent with the expected item order. CONCLUSIONS: The items testing
      resting-state reflexes may threaten the assessment's dimensionality. With reflex
      items removed, the assessment is a unidimensional measure of volitional movement.
      The Rasch-generated item-difficulty order challenges the hierarchical structure
      implied by the instrument's underlying conceptual framework.

PMID- 17532893
TI  - Assessing subjective fall concerns in residential living seniors: development of
      the activities-specific fall caution scale.
AB  - OBJECTIVES: To examine subjective fall concerns of seniors in residential care
      and to develop a tool applicable to both nursing home and assisted living
      settings. DESIGN: Used focus groups with residents and staff for construct
      examination and item generation; surveyed staff and interviewed residents for
      item verification; and conducted psychometric testing using Rasch analysis for
      scale refinement. SETTING: Seventeen residential care facilities in Ontario,
      Canada. PARTICIPANTS: Convenience samples totaling 57 staff and 234 residents.
      INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: The Activities-specific Fall
      Caution (AFC) Scale, developed inductively with residents and staff, with items
      pertaining to residential living (eg, moving around a room full of people,
      furniture, or walkers). RESULTS: Resident terms (being cautious or careful) and
      qualifications (whether alone and proximity of gait aids) guided tool
      development. Rasch analysis showed that the final 13-item AFC Scale was
      hierarchic and unidimensional, with good person (.86) and item (.95) reliability.
      CONCLUSIONS: The AFC scale is a promising new tool for assessing subjective fall
      concerns in residential care residents. This tool can be administered via
      interview in about 10 minutes to most residents with Mini-Mental State
      Examination scores of 12 or greater, using practice questions to determine
      understanding and a 4-point color response card similar to a traffic light to
      facilitate responding.

PMID- 17532894
TI  - Reliability, construct validity, and clinical feasibility of the activities
      specific fall caution scale for residential living seniors.
AB  - OBJECTIVE: To examine the reliability, validity, and feasibility of the
      Activities-specific Fall Caution (AFC) Scale. DESIGN: Cross-sectional studies
      with test-retest and interrater reliability. SETTING: Residential care facilities
      in Ontario, Canada: 10 in study 1 and 6 in study 2. PARTICIPANTS: Convenience
      samples of 101 and 31 residents. INTERVENTIONS: Not applicable. MAIN OUTCOME
      MEASURES: In study 1, the AFC Scale was readministered to 44 residents, 64 were
      assessed using the Berg Balance Scale, Timed Up & Go, and Self-Paced Walk Test,
      and the Nursing Home Life-Space Diameter was completed for 80 residents. In study
      2, staff administered the AFC Scale to 31 residents on 2 occasions. RESULTS: In
      study 1, test-retest reliability (intraclass correlation coefficient [ICC]) was
      .87 (95% confidence interval, .78-.93). AFC scores were associated with physical
      performance and mobility patterns (P<.001) and able to discriminate on the basis
      of gait aid use (P<.001), balance disorders (P<.05), and transfer assistance and
      walk speed (P<.01). Comparatively, general fear of falling showed weaker
      associations and a sex bias. In study 2, staff administration was fairly
      consistent (ICC=.71) and similar associations emerged for AFC scores.
      CONCLUSIONS: The AFC Scale shows good reproducibility, convergent and
      discriminative validity, and is feasible for clinical as well as research use.

PMID- 17532895
TI  - Social determinants of discharge destination for patients after stroke with low
      admission FIM instrument scores.
AB  - OBJECTIVE: To investigate the effects of immigrant status (via country of birth),
      marital status, and area-based socioeconomic status (SES) on discharge
      destination after stroke for those with low admission scores on the FIM
      instrument. DESIGN: Cross-sectional study. SETTING: Inpatient rehabilitation ward
      at an urban community hospital in Australia. PARTICIPANTS: A total of 326
      inpatients admitted for rehabilitation poststroke. INTERVENTION:
      Multidisciplinary rehabilitation. MAIN OUTCOME MEASURE: Discharge home versus
      nursing home. RESULTS: A total admission FIM score of 75 or lower was associated
      with a higher probability of nursing home discharge. Married patients with a
      total FIM admission score of 75 or lower were significantly more likely to be
      discharged home, after adjusting for immigrant status, type and side of stroke,
      sex, and age (odds ratio, 6.07; 95% confidence interval, 1.65-22.40; P<.01). This
      effect was also observed for low motor and cognition components of FIM admission
      score. The effect of immigrant status did not remain significant after adjusting
      for marital status. Area-based SES and stroke characteristics did not
      substantially attenuate the relationship between immigrant status, marital
      status, and discharge location. CONCLUSIONS: Marital status is a significant
      determinant of discharge destination. Immigrant status and area-based SES were
      not significant predictors of discharge disposition.

PMID- 17532896
TI  - Predicting walking at discharge from inpatient rehabilitation after a traumatic
      spinal cord injury.
AB  - OBJECTIVE: To investigate how injury level and American Spinal Injury Association
      Impairment Scale (AIS) grade at rehabilitation admission are related to walking
      at discharge after traumatic spinal cord injury (SCI). DESIGN: Retrospective
      study. SETTING: Comprehensive rehabilitation hospital. PARTICIPANTS: A total of
      343 adult inpatients with traumatic SCI. INTERVENTIONS: Not applicable. MAIN
      OUTCOME MEASURE: FIM instrument walking rating of 3 (moderate assistance) or
      higher at discharge. RESULTS: Significantly more subjects admitted with AIS grade
      C (28.3%) than AIS grade A or B injuries (0.9%) walked at discharge.
      Significantly more subjects admitted with AIS grade D (67.2%) than AIS grade C
      (28.3%) injuries walked at discharge. Level of injury did not significantly
      affect walking after AIS grade C or D injuries. Being 50 years or older had a
      significant negative affect on walking in subjects with AIS grade D but not AIS
      grade C injuries. CONCLUSIONS: Admission AIS grades give information about
      walking for treatment and discharge planning during acute inpatient
      rehabilitation, including the following: (1) patients admitted with AIS grade C
      injuries should not be considered functionally complete when predicting walking
      (FIM score > or = 3; no more than moderate assistance) at discharge, (2) level of
      injury does not affect walking for those with AIS grade C or D injuries, and (3)
      being 50 years or older has a significant negative affect on walking in subjects
      with AIS grade D but not AIS grade C injuries.

PMID- 17532897
TI  - A guideline-driven assessment of need for cardiovascular disease risk
      intervention in persons with chronic paraplegia.
AB  - OBJECTIVE: To examine percentages of persons with chronic paraplegia who qualify
      for lipid-lowering therapeutic lifestyle intervention (TLI) as assessed by
      authoritative guidelines. DESIGN: Cross-sectional. SETTING: Academic medical
      center. PARTICIPANTS: Forty-one subjects (mean age +/- standard deviation, 34+/
      11 y) with motor-complete paraplegia (American Spinal Injury Association grade A
      or B) at T6-L1 levels for greater than 2 years. INTERVENTIONS: Not applicable.
      MAIN OUTCOME MEASURES: Percentages of subjects qualifying for TLI were
      independently assessed and then compared using National Cholesterol Education
      Project Adult Treatment Panel (ATP) II (1994) and ATP III (2002) Guidelines.
      RESULTS: A total of 34.1% of subjects qualified for intervention based on the ATP
      II Guidelines and 63.4% based on ATP III (chi1(2) test=4.53; 2-tailed, P=.003).
      Seventy-six percent (31/41) of study participants had high-density lipoprotein
      cholesterol levels below the high-risk criterion of 40 mg/dL established by ATP
      III. Almost one third of subjects had hypertension, and 34.1% satisfied criteria
      for diagnosis of the metabolic syndrome. CONCLUSIONS: A high percentage of young,
      apparently healthy people with chronic paraplegia are at risk for cardiovascular
      disease and qualify for lipid-lowering TLI. Updated guidelines of the ATP III
      have increased the urgency for early risk assessment and intervention.

PMID- 17532898
TI  - The relationship between basal metabolic rate and femur bone mineral density in
      men with traumatic spinal cord injury.
AB  - OBJECTIVES: To investigate the relationship between basal metabolic rate (BMR)
      and hip bone mineral density (BMD) in people with spinal cord injury (SCI) and to
      determine whether neurologic factors contribute to this relationship. DESIGN:
      Cross-sectional study. SETTING: Inpatient SCI unit in a rehabilitation hospital.
      PARTICIPANTS: Thirty men with chronic (time since injury, >1 y) traumatic SCI
      with an American Spinal Injury Association Impairment Scale grade A or B.
      Subjects' mean age was 32 years (range, 20-45 y). INTERVENTIONS: All participants
      were evaluated with neurologic examination to define the level and severity of
      injury. BMR was determined by indirect calorimetry, and BMD was determined by
      dual-energy x-ray absorptiometry (DXA). Patients were allocated to osteoporotic,
      osteopenic, and normal bone density groups according to World Health Organization
      criteria. DXA was used also to estimate lean- and fat-tissue mass (in kilograms)
      by standard methods. DXA measurements were performed on the same day as BMR
      analysis. MAIN OUTCOME MEASURES: DXA and indirect calorimetry. RESULTS: BMR
      correlated significantly with BMD of the total femur, femur neck, trochanter, and
      shaft. However, there was no correlation between BMR and femur Ward's triangle.
      These correlations were stronger in patients with tetraplegia. There was a
      moderate correlation between BMR and lean tissue mass (r = .66, P < .001),
      although femur BMD values did not correlate with lean tissue mass in our study
      group (P > .05). CONCLUSIONS: BMR is closely associated with BMD in men with SCI.

PMID- 17532899
TI  - The assessment of walking capacity using the walking index for spinal cord
      injury: self-selected versus maximal levels.
AB  - OBJECTIVES: To assess (1) the frequency and magnitude of differences between self
      selected and maximal walking capacity following spinal cord injury (SCI) by using
      the Walking Index for Spinal Cord Injury (WISCI) and (2) how these levels differ
      in efficiency and velocity. DESIGN: Prospective cohort. SETTING: Academic medical
      center. PARTICIPANTS: Fifty people with chronic incomplete SCI. INTERVENTIONS:
      Not applicable. MAIN OUTCOME MEASURES: Subjects ambulated at the level used in
      the community (self-selected WISCI) and the highest level possible (maximal
      WISCI). Velocity (in m/s), Physiological Cost Index (PCI), and Total Heart Beat
      Index (THBI) were calculated. Differences were compared using the paired t test
      (parametric) or Wilcoxon signed-rank test (nonparametric). RESULTS: For 36
      subjects, maximal WISCI was higher than self-selected WISCI; 21 subjects showed
      an increase of 3 levels or more. Ambulatory velocity was higher for self-selected
      WISCI compared with maximal WISCI (.68 m/s vs .56 m/s, P<.001). PCI and THBI at
      self-selected WISCI were lower than at maximal WISCI (PCI, 0.99 beats/m vs 1.48
      beats/m, P<.001; THBI, 3.39 beats/m vs 4.75 beats/m, P<.001). CONCLUSIONS: Many
      people with chronic SCI are capable of ambulating at multiple levels. For these
      people, ambulation at self-selected WISCI was more efficient as evidenced by
      greater velocity and decreased PCI and THBI. The findings have implications for
      assessing walking capacity within the context of clinical trials.

PMID- 17532900
TI  - Comparison of spatiotemporal and energy cost of the use of 3 different walkers
      and unassisted walking in older adults.
AB  - OBJECTIVE: To compare temporal, spatial, and oxygen costs of gait while elderly
      subjects walked without an assistive device, with a new assistive device, and
      with 2 other commercially available assistive devices. DESIGN: Descriptive,
      repeated measures. SETTING: University-based research laboratory. PARTICIPANTS:
      Thirteen healthy older subjects who could walk without an assistive device.
      INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Gait speed, normalized gait
      speed, cadence, stride lengths, 5-minute walk distance and gait speed, oxygen
      consumption (Vo2) per meter walked, respiratory exchange ratio (RER) per meter
      walked, and minute ventilation per meter walked. RESULTS: Gait speed, normalized
      gait speed, and stride lengths decreased when the Merry Walker device was used,
      compared with walking without an assistive device. Outcome measures when walking
      with either the wheeled walker or the WalkAbout did not differ significantly from
      walking without a device except for a faster cadence with the WalkAbout. The
      distance walked and gait speed were decreased and the RER and minute ventilation
      were increased during the 5-minute walk with the Merry Walker compared with
      normal walking. The Vo2 was higher with the wheeled walker and Merry Walker than
      when walking without an assistive device, but there was no difference when the
      WalkAbout was used. CONCLUSIONS: Older adults walked in the new assistive device,
      the WalkAbout, with parameters that did not differ significantly from their gait
      without a device. The oxygen demands of walking were similar to unassisted
      walking for the WalkAbout, but were higher for the wheeled walker and Merry
      Walker. These results may help guide the prescription of assistive devices for
      older adults.

PMID- 17532901
TI  - Perceived and actual memory, concentration, and attention problems after whiplash
      associated disorders (grades I and II): prevalence and predictors.
AB  - OBJECTIVES: To evaluate neuropsychologic test performance of people with whiplash
      associated disorders (WADs) and to compare the performance of those who report
      cognitive symptoms (CS+) with those who do not (CS-). DESIGN: Cross-sectional
      analysis of a convenience sample. SETTING: Outpatient research center.
      PARTICIPANTS: People with recent WADs (N=203) who responded to advertisements to
      participate in a treatment study. INTERVENTIONS: Not applicable. MAIN OUTCOME
      MEASURES: Participants completed a history form including information about
      demographics, medical history, description of the collision, litigation status, a
      set of instruments designed to assess neck disability, pain severity, depressed
      mood, pain-related anxiety, and fear of potentially stressful neck movements and
      completed a generic 38-item symptom checklist that included items about memory
      and concentration problems. They also were administered the third revision of the
      Wechsler Memory Scale (WMS-III) and the Trail-Making Test (TMT). Participants
      were designated CS+ if they endorsed memory problems or concentration problems on
      the symptom checklist and CS- if they did not endorse either type of problem.
      RESULTS: CS+ and CS- participants performed equally well on the TMT and on all
      WMS-III indexes. Univariate analyses revealed that CS+ participants scored higher
      than CS- participants in neck disability, pain severity, depression, pain-related
      anxiety, and fear of neck movements. They also endorsed more items on the symptom
      checklist, including items (eg, skin rash) that had no obvious connection with
      WADs. In a multivariate analysis, CS+ versus CS- status was predicted only by the
      total number of items endorsed on the symptom checklist. CONCLUSIONS: Reports of
      memory or concentration problems appear to be indicators of heightened somatic
      vigilance rather than indicators of actual neuropsychologic deficits. Our results
      suggest that it is reasonable for physicians to defer neuropsychologic testing or
      advanced imaging studies on WAD patients who report cognitive symptoms but no
      other indicators of brain injuries and instead to rely on reassurance and
      education about the normal aftermath of motor vehicle collisions.

PMID- 17532902
TI  - The evaluation of electrodermal properties in the identification of myofascial
      trigger points.
AB  - OBJECTIVES: To determine whether skin resistance measurements can objectively
      identify the location of myofascial trigger points (MTPs) and to differentiate
      between 3 states. DESIGN: Static group comparison. SETTING: Climate-controlled
      laboratory. PARTICIPANTS: Forty-nine participants (age, 20.5+/-2.6 y) were
      assigned to 1 of 3 groups based on clinical examination result: absent (n=21),
      latent (n=16), or active (n=12) MTP. INTERVENTIONS: Not applicable. MAIN OUTCOME
      MEASURE: Skin resistance (in kilo-ohms). RESULTS: The 16 data points were divided
      into 3 categories for analysis: MTP site, surrounding tissue proximal to the MTP
      (first ring), and area furthest from the MTP (second ring). There was a
      significant increase in skin resistance between the MTP (403.64+/-124.73 kOmega),
      first ring (419.66+/-123.04 kOmega), and second ring (454.61+/-163.19 kOmega)
      (P<.01). The measurements did not differ significantly between the 3 MTP states.
      CONCLUSIONS: The changes in skin resistance between the MTP and the surrounding
      tissue support the inclusion of this technique to help identify MTPs. The
      similarity between MTP states warrants investigation into the physiologic
      differences at specific anatomic locations.

PMID- 17532903
TI  - Heat shock protein expression in rat skeletal muscle after repeated applications
      of pulsed and continuous ultrasound.
AB  - OBJECTIVE: To determine whether repeated ultrasound treatments are capable of
      increasing the expression of heat shock protein (HSP) 72 and HSP 25 in rat
      skeletal muscles. DESIGN: In vivo, experimental, controlled study. SETTING:
      Animal laboratory. ANIMALS: Male Sprague-Dawley rats (n=9). INTERVENTIONS:
      Ultrasound (1MHz, 15 min, 2.0 cm2 transducer) continuous at 1.0 W/cm2 spatial
      average temporal average intensity (CONTUS) or pulsed at 2.0 W/cm2 spatial
      average temporal peak intensity 50% duty cycle (PULS50) was applied on 4
      consecutive days to the lower leg muscles of 1 hindlimb in each rat (n=9). MAIN
      OUTCOME MEASURES: Twenty-four hours after the final ultrasound application,
      hindlimb muscles were removed, weighed, and assessed for HSP 72 and HSP 25
      content by Western blotting. Bands from blots were quantified and data were
      assessed using t tests (alpha=.05). RESULTS: Ultrasound did not affect core or
      contralateral hindlimb muscle temperature. Average muscle temperatures during the
      final day ultrasound treatments were 38.71 degrees +/-0.30 degrees C when using
      PULS50 and 38.16 degrees +/-0.57 degrees C when using CONTUS. PULS50
      significantly increased HSP 25 content in the plantaris and soleus muscles and
      HSP 72 content in the plantaris muscles. CONTUS significantly increased HSP 72
      content in the white gastrocnemius muscle. CONCLUSIONS: HSPs can be induced in
      skeletal muscle when ultrasound is used on a repeated basis to treat soft tissue.

PMID- 17532904
TI  - Genu recurvatum in hemophilia: a case report.
AB  - Hemorrhages in the musculoskeletal system of patients with hemophilia give rise
      to a number of disabilities requiring rehabilitative measures. The knee is the
      most commonly affected joint. Recurrent hemorrhages in the knee joint can cause
      arthropathy and flexion deformity. The current literature does not reveal
      development of genu recurvatum from repeated hemorrhages. This report presents a
      patient with hemophilia who developed a genu recurvatum deformity. We have
      discussed the clinical presentation, probable cause, and the management of the
      patient, and have included a brief review of the epidemiology of this deformity
      along with management options.

PMID- 17532905
TI  - Hand strength and perceived manual ability among patients with multiple
      sclerosis.
AB  - OBJECTIVES: To describe hand function among patients with multiple sclerosis (MS)
      and to examine the relationship between strength and self-reported abilities.
      DESIGN: Cross-sectional study using a convenience sample. SETTING: Outpatient
      department at a rehabilitation center. PARTICIPANTS: Forty-four community
      dwelling adults with MS (mean age, 49+/-9 y; range, 34-68 y) who were monitored
      by rehabilitation practitioners. INTERVENTIONS: Not applicable. MAIN OUTCOME
      MEASURES: Grip and pinch (tip, lateral, palmar) strengths and Manual Ability
      Measure (MAM-36). RESULTS: When compared with the 50- to 54-year-old female
      norms, the pinch and grip strengths of the sample were lower. MAM-36 correlated
      moderately with right pinch (tip, lateral, palmar) strengths (r range, .51-.59;
      P<.01). CONCLUSIONS: Manual ability seems to be more associated with pinch than
      grip strengths, probably because finger strength and dexterity are both needed to
      perform many hand tasks.

PMID- 17532906
TI  - An electric stimulation cycling protocol for gait in incomplete spinal cord
      injury.
AB  - OBJECTIVE: To determine the feasibility and impact of an outpatient, electric
      stimulation cycling (ESC) protocol on a patient with incomplete spinal cord
      injury (SCI). DESIGN: Pre-post case study. SETTING: Outpatient rehabilitation
      hospital. PARTICIPANT: A 24-year old man with an incomplete SCI occurring 25
      months before study entry at the T12-L1 level. INTERVENTION: A 2-phase, 10-week
      ESC intervention occurring 3 days a week. Phase 1 provided 30-minute ESC sessions
      at increasing resistance with electric stimulation applied to the quadriceps and
      hamstrings; phase 2 required cycling independently (ie, without stimulation) at
      maximal effort for increasing lengths of time. MAIN OUTCOME MEASURES: Gait
      velocity, stride length, and step length, all collected during a 10-meter walking
      test, and the Walking Index of Spinal Cord Injury-II (WISCI-II). RESULTS: During
      phase 1, the patient quickly increased workload, session duration, and distance;
      during phase 2, duration that the subject was able to cycle without stimulation
      increased markedly. After the entire intervention, the subject exhibited
      diminished edema, new ability to voluntarily step, new ability to voluntarily
      dorsiflex the ankle and voluntarily flex the toe, and new ability to perform
      valued activities, such as transfers. He also exhibited increased mean gait
      velocity (.33 m/s), left (.11 m) and right (.07 m) stride length, left (.06 m)
      and right (.05 m) step length, and a 10-point WISCI-II increase. The subject was
      also able to discontinue use of several medications after intervention.
      CONCLUSIONS: SCI patients' endurance and gait deficits can possibly be
      effectively addressed on an outpatient basis and with minimal assistance by using
      this regimen.

PMID- 17532907
TI  - A comparative study of conventional and energy-storing prosthetic feet in high
      functioning transfemoral amputees.
AB  - OBJECTIVE: To compare the results of gait analysis, timed walking tests, and
      socket comfort for transfemoral amputees wearing initially a Multiflex
      conventional prosthetic foot and then a Vari-Flex energy-storing prosthetic foot.
      DESIGN: Experimental crossover trial. SETTING: A regional prosthetic and amputee
      rehabilitation tertiary referral center in a teaching hospital. PARTICIPANTS: Six
      established unilateral transfemoral prosthetic users. INTERVENTIONS: Not
      applicable. MAIN OUTCOME MEASURES: Gait analysis, a timed walking test, and a
      Prosthetic Socket Fit Comfort Score for each amputee wearing the Multiflex foot
      and then repeated wearing the Vari-Flex foot. RESULTS: Wearing the Vari-Flex
      foot, our subjects walked faster in the gait lab (1.38 +/- 0.13 m/s, P < .001)
      and took more equal step lengths at fast speed (1.063 +/- 0.05, P < .05). They
      also had greater peak ankle dorsiflexion at push-off on the prosthetic side (18.3
      degrees +/-4.73 degrees, P<.001) and 3 times as much power from the prosthetic
      ankle at push-off (1.13 +/- 0.22 W/kg, P < .001). There were no significant
      changes in temporal symmetry or loading of the prosthetic limb, in the timed
      walking test with each foot, or in the comfort score. CONCLUSIONS: A transfemoral
      amputee who wears an energy-storing foot can have a more symmetric gait with
      regard to some measures of spatial symmetry, kinetics, and kinematics than one
      who wears a conventional foot. However, in this study important aspects such as
      more symmetric loading and comfort did not differ significantly between the 2
      foot types.

PMID- 17532908
TI  - Power mobility device provision: understanding Medicare guidelines and advocating
      for clients.
AB  - The Centers for Medicare and Medicaid (CMS) issued a new national coverage
      determination (NCD) for mobility assistive equipment (MAE) including wheelchairs
      in May 2005. CMS then issued a Final Rule in April 2006 that outlined significant
      changes required for documentation for prescribing MAE. Other insurance providers
      have since adopted and sometimes modified the NCD criteria and have begun to
      apply these criteria according to their own interpretations because some of the
      criteria are vague. In this report, we introduce a case example to show the
      components of the CMS NCD criteria, what was intended but poorly described in the
      language, how insurance providers may misinterpret or alter the criteria, and how
      clinicians can act as advocates.

PMID- 17532912
TI  - Commerce versus care: troubling trends in the ethics of esthetic dentistry.

PMID- 17532909
TI  - Preserving upper-limb function in spinal cord injury.

PMID- 17532913
TI  - Can a new smile make you look more intelligent and successful?
AB  - A smile has a tremendous impact on perceptions of one's attractiveness and one's
      personality. Previous psychological research has shown that attractive people are
      perceived as more successful, intelligent, and friendly. Research extends these
      findings by demonstrating that teeth alone can have an impact on overall
      attractiveness and perceptions of personality attributes. The results of the
      study discussed in this article extend the attractiveness research and
      demonstrate that one's smile is an important part of the physical attractiveness
      stereotype. One's smile clearly plays a significant role in the perception that
      others have of our appearance and our personality.

PMID- 17532914
TI  - Smile design.
AB  - Many scientific and artistic principles considered collectively are useful in
      creating a beautiful smile. The evaluation and analysis of the face, lips,
      gingival tissues and teeth are all considered in this process. Recognizing the
      ideal as a goal provides a direction for diagnosis and treatment planning for
      smile rejuvenation. This article focuses on the dental and dental-facial
      composition involved in smile design. Basic facial esthetics are reviewed as a
      guideline for facial analysis.

PMID- 17532915
TI  - Vital tooth whitening.
AB  - Vital tooth whitening, when administered correctly, is by all accounts one of the
      safest, most conservative, least expensive, and most effective aesthetic
      procedures currently available to patients. This article traces the evolution of
      the technology, describes what is known about the mechanism of action and
      explores such issues as toxicology and side effects associated with tooth
      whitening. The article also describes the various tooth-whitening systems, which
      include dentist-supervised night-guard bleaching, in-office or power bleaching,
      and bleaching with over-the-counter bleaching products. Combination treatments
      and light-activated treatments are also discussed. Finally, the article
      summarizes the areas of research needed in this field.

PMID- 17532916
TI  - New developments in dental adhesion.
AB  - Numerous simplified adhesives have been introduced to the dental market within
      the last few years, sometimes without comprehensive testing to validate the
      performance claimed by the respective manufacturers. Mild self-etch adhesives are
      unable to etch enamel to provide adequate retention for bonded restorations.
      Although high early resin-dentin bond strength values can be achieved with some
      self-etch adhesives, their resistance to thermal and mechanical stresses over
      time is disappointing. In light of the current drawbacks attributed to all-in-one
      self-etch adhesives, etch-and-rinse adhesives are still the benchmark for dental
      adhesion in routine clinical use. This article summarizes current issues and
      factors related to the performance of adhesives.

PMID- 17532917
TI  - Aesthetic anterior composite restorations: a guide to direct placement.
AB  - Mastering anterior direct composite restorations is a necessity for the
      contemporary clinician who appreciates and understands the art and science of
      cosmetic dentistry. In the esthetic zone, composite bonding procedures are
      considered the most conservative and least invasive technique to return missing,
      diseased, and unsightly tooth structure to enhanced color, form, and function.
      Composites' attractiveness and popularity are easy to explain because these
      restorations have excellent esthetic potential, very good to excellent prognosis,
      and a reasonable fee. Composites are the most versatile restorative material
      available to the dental professional, especially for the esthetic-conscious
      patients. For composite restorations to mimic natural tooth structure, the
      clinician must have a comprehensive understanding of the material science and
      techniques involved in direct bonding procedures.

PMID- 17532918
TI  - Abrasive finishing and polishing in restorative dentistry: a state-of-the-art
      review.
AB  - Effective finishing and polishing of dental restorations not only result in
      optimal aesthetics but also provide for acceptable oral health of soft tissues
      and marginal integrity of the restorative interface. This review of abrasive
      technology in dentistry provides an overview of basic principles of abrasive
      science and considers some research concerning clinically relevant questions. The
      article also discusses some recent innovations in finishing and polishing
      devices. This review brings forward some newly published, outcome-based
      information concerning the relevance and importance of an effective knowledge of
      finishing and polishing techniques and materials. The overall aim is to provide
      an enhanced awareness and broader knowledge of the principles and tools available
      to produce optimal surface finishing and integrity in dental restoratives.

PMID- 17532919
TI  - Porcelain laminate veneers: reasons for 25 years of success.
AB  - This article discusses failures that could occur if meticulous attention is not
      given to details such as planning the case, conservative (enamel saving)
      preparation of teeth, proper selection of ceramics to use, proper selection of
      the materials and methods of cementation of these restorations, proper finishing
      and polishing of the restorations, and proper planning for the continuing
      maintenance of these restorations. Some concerns as to newer products and methods
      and their effect on the continued success of this modality of treatment are also
      addressed.

PMID- 17532920
TI  - Porcelain laminate veneers: minimal tooth preparation by design.
AB  - Porcelain laminate veneers have been one of the most used restorations for
      aesthetics. Aesthetics is a subject that is objective and necessitates excellent
      communication among the dentist, patient, and ceramist. The case must be
      carefully selected and treatment planned. The use of mock-ups, followed by a wax
      model, aesthetic pre-evaluative temporaries, and silicone index, provides the
      best aesthetic, phonetic, and functional outcome and allows for better
      communication with the patient and laboratory. The use of permanent diagnostic
      provisionals could have a further impact on this solid communication. Patients
      have the chance to evaluate the aesthetics, function, and phonetics not only by
      themselves but also with their immediate circle of family or friends.

PMID- 17532921
TI  - Adhesion to porcelain and metal.
AB  - Some compelling clinical benefits of porcelain and metal adhesion are presented.
      Current concepts for metal adhesion are reviewed, including modifications of
      metal surface and resin chemistry. Porcelain adhesion is reviewed, including
      little-known methods that use silane but no hydrofluoric acid etching. Clinical
      protocols for use of metal and porcelain adhesives are presented.

PMID- 17532922
TI  - Cements for use in esthetic dentistry.
AB  - Dental cements are designed to retain restorations, appliances, and post and
      cores in a stable and, presumably, long-lasting position in the oral environment.
      Conventional glass ionomer and zinc phosphate cements are among the most popular
      materials for luting metallic restorations and posts, whereas resin-based cements
      are preferred for esthetic applications. Successful cementation of esthetic
      restorations is largely dependent on the appropriate treatment and silane
      application to the internal surface of the restoration. Clinicians are frequently
      advised to use three-step total-etch or two-step self-etch adhesive for luting
      purposes to avoid problems of incompatibility between adhesives and chemical- or
      dual-cure cements. A reliable cementation procedure can only be achieved if the
      operator is aware of the mechanisms involved and the material limitations.

PMID- 17532923
TI  - Clinical steps to predictable color management in aesthetic restorative
      dentistry.
AB  - The shade matching of a restoration is the critical final step in aesthetic
      restorative dentistry once morphology and occlusion are addressed. This article
      describes a seven-step approach to successful shade matching: patient and tooth
      evaluation, image capture and shade analysis, communication, interpretation,
      fabrication, verification, and placement of restoration. A step-by-step protocol
      to shade matching is comprehensively outlined through a case study using a
      combination of technology-based instrumentation, conventional techniques, and
      reference photography.

PMID- 17532924
TI  - A multidisciplinary approach to esthetic dentistry.
AB  - Today's dentist does not just repair teeth to make them better for chewing.
      Increasingly, his or her work involves esthetics. With patients demanding more
      attractive teeth, dentists now must become more familiar with the formerly
      independent disciplines of orthodontics, periodontics, restorative dentistry, and
      maxillofacial surgery. This article provides a systematic method of evaluating
      dentofacial esthetics in a logical, interdisciplinary manner. In today's
      interdisciplinary dental world, treatment planning must begin with well-defined
      esthetic objectives. By beginning with esthetics, and taking into consideration
      the impact on function, structure, and biology, the clinician will be able to use
      the various disciplines in dentistry to deliver the highest level of dental care
      to each patient.

PMID- 17532925
TI  - Esthetic considerations when splinting with fiber-reinforced composites.
AB  - The primary reasons for splinting and stabilizing teeth are to connect them for
      the purpose of replacing missing teeth or as an adjunct to periodontal therapy.
      Although the restorations must be planned to withstand the functional
      requirements of occlusion and mastication, esthetic considerations must also be
      taken into account. The challenge in creating an esthetic result with fiber
      reinforced composite splints is that there is limited space in the connector
      region to create the three-dimensional effect required to give teeth the
      appearance of individuality. Careful planning in the diagnosis and treatment of
      the fiber splint is essential to allow for adequate tooth preparation to give the
      illusion of nonsplinted teeth. When missing teeth are replaced with a fiber
      reinforced, direct, fixed partial denture, the pontic must be created to achieve
      an esthetically pleasing result.

PMID- 17532926
TI  - Laser use for esthetic soft tissue modification.
AB  - In esthetic dentistry, expanding the evaluation beyond the teeth is necessary to
      achieve a truly desirable result. The lips, attached and unattached mucosa, free
      gingival margin, and osseous position and contours must be considered and changed
      if necessary. Although many treatment modalities are available to accomplish
      these modifications, the use of lasers of varying wavelengths provides advantages
      not possible by other means. Lasers are often thought of as generic instruments,
      but different laser wavelengths function differently, and each has its place in
      the esthetic continuum. Diode, neodymium:YAG, CO(2) and erbium lasers each have
      advantages that can be exploited to maximum effect and disadvantages that must be
      taken into consideration. A thorough understanding of their mechanism of action,
      their tissue effects, and laser safety is vital to obtaining excellent results.

PMID- 17532927
TI  - Advanced concepts in implant dentistry: creating the "aesthetic site foundation".
AB  - To obtain optimal and predictable aesthetics, deficiencies caused by soft and
      particularly hard tissue loss can be managed by various methods, such as
      orthodontic tooth eruption, socket preservation, and guided bone regeneration.
      However, in complex cases, these methods are often insufficient. Here, the
      authors introduce advanced concepts in aesthetic implant dentistry, such as
      "Aesthetic Site Foundation", "Aesthetic Guided Bone Regeneration" and "Implant
      Rectangle" that will guide the clinician in the quest to optimal aesthetic
      outcomes.

PMID- 17532928
TI  - Prosthesis-patient mismatch in the mitral position: old concept, new evidences.

PMID- 17532929
TI  - Translational research: is there a future?

PMID- 17532930
TI  - Lung-volume reduction surgery: a vanishing operation?

PMID- 17532931
TI  - Ten traps for the unwary in surgical series: a case study in mesothelioma
      reports.

PMID- 17532932
TI  - Fluorine-18 fluorodeoxyglucose positron emission tomographic maximal standardized
      uptake value predicts survival independent of clinical but not pathologic TNM
      staging of resected non-small cell lung cancer.
AB  - OBJECTIVES: Positron emission tomographic maximal standardized uptake value has
      been shown to predict survival after resection of non-small cell lung cancer. The
      relative prognostic benefit of maximal standardized uptake value with respect to
      other clinical/pathologic variables has not been defined. METHODS: We reviewed
      patients who had positron emission tomographic imaging and an R0 resection for
      non-small cell lung cancer between January 1, 2000, and December 31, 2004,
      without induction or adjuvant therapy. The associations between overall survival,
      histology, pathologic TNM stage, pathologic tumor diameter, and standardized
      uptake value were tested. RESULTS: Four hundred eighty-seven patients met the
      study criteria. Median follow-up was 25.8 months. By using the median values for
      tumor size (2.5 cm) and standardized uptake value (5.3), standardized uptake
      value was an independent predictor of survival (P = .03), adjusting for tumor
      size (P = .02) and histology (P < .01). The optimal standardized uptake value for
      stratification was identified as 4.4, and this value was identified as an
      independent predictor of survival (P = .03) after adjusting for clinical TNM
      stage. Standardized uptake value was not an independent predictor of survival (P
      = .09), adjusting for pathologic TNM stage (stage IA vs IB vs stage II-IV, P <
      .01). CONCLUSIONS: Standardized uptake value does not add to the prognostic
      significance of pathologic TNM stage. Standardized uptake value was an
      independent prognostic factor from clinical TNM stage.

PMID- 17532934
TI  - Long-term effects of thoracic sympathectomy on microcirculation in the hands of
      patients with primary Raynaud disease.
AB  - OBJECTIVE: Videothoracoscopic sympathecomy is a widely used treatment modality in
      patients with severe Raynaud disease, but the reported late results are less than
      favorable. There have been no direct studies of the long-term effect of
      sympathectomy on microcirculation in the hands of these patients. METHODS: In 25
      patients with Raynaud disease treated with videothoracoscopic Th2-Th4
      sympathectomy, we performed basal laser-Doppler flowmetry and measured the
      maximal refilling time after 1-minute occlusion measurements preoperatively and
      at 1 week, 6 months, and 1, 2, 3, and 5 years after the sympathectomy. The
      results were compared with the same measurements obtained in the group of 50
      healthy individuals. RESULTS: The patients' symptom severity was assessed by
      using the visual analogue scale. The basal capillary flow and the maximal
      refilling time improved after the sympathectomy to a level not different from
      that seen in the healthy population, and the effect was maintained during the 5
      year follow-up period. The patients' symptom severity scores diminished to zero
      in the early postoperative period and increased to 28% of their initial value 5
      years after the operation. CONCLUSIONS: The videothoracoscopic Th2-Th4
      sympathectomy produces excellent and long-lasting improvement of microcirculation
      function in patients with Raynaud disease. The mild return of symptoms might be
      due to factors other than the capillary blood flow alterations.

PMID- 17532935
TI  - Lung-volume reduction surgery for pulmonary emphysema: Improvement in body mass
      index, airflow obstruction, dyspnea, and exercise capacity index after 1 year.
AB  - OBJECTIVES: We hypothesized that lung-volume reduction surgery for pulmonary
      emphysema would improve body mass index, airflow obstruction, dyspnea, and
      exercise capacity (BODE) index, a multidimensional predictor of survival in
      chronic obstructive pulmonary disease. We also aimed to identify preoperative
      predictors of improvement in the BODE index. METHODS: In a prospective cohort
      study of patients undergoing lung-volume reduction surgery at our center, with
      the methodology of the National Emphysema Treatment Trial, we compared clinical
      characteristics before and 1 year after surgery with the Wilcoxon signed rank
      test. Changes in the BODE index were correlated with preoperative variables with
      the Spearman correlation coefficient. RESULTS: Twenty-three patients with
      predominantly upper-lobe pulmonary emphysema underwent lung-volume reduction
      surgery (14 by video-assisted thoracoscopic surgery, 9 by median sternotomy).
      There were no postoperative or follow-up deaths. The BODE index improved from a
      median of 5 (interquartile range 4-5) before surgery to 3 (interquartile range 2
      4) 1 year after surgery (P < .0001). Improvements were seen in the lung function
      and dyspnea components of the BODE index. Lower preoperative 6-minute walk
      distance and lower postwalk Borg fatigue scores were each associated with greater
      improvement in the BODE index after 1 year. CONCLUSION: Lung-volume reduction
      surgery for pulmonary emphysema improved the BODE index in patients with
      predominantly upper-lobe disease. Lower preoperative 6-minute walk distance
      correlated with greater improvement in the BODE index.

PMID- 17532936
TI  - Idiopathic postpneumonectomy pulmonary edema: hyperinflation of the remaining
      lung is a potential etiologic factor, but the condition can be averted by
      balanced pleural drainage.
AB  - OBJECTIVES: Idiopathic postpneumonectomy pulmonary edema is a leading cause of
      mortality after pneumonectomy. Postoperative hyperinflation of the remaining lung
      is an etiologic factor. We have demonstrated avoidance of postpneumonectomy
      pulmonary edema solely by changing management of the pneumonectomy space to a
      balanced drainage system. In sheep, we tested the following hypothesis: (1)
      Postoperative induced hyperinflation of the remaining lung can cause
      postpneumonectomy pulmonary edema. (2) A balanced drainage system can prevent its
      development. METHODS: We performed 37 right-sided pneumonectomies in adult sheep.
      In experiment 1, after surgery, 10 sheep had continuous suction (5 kPa) applied
      through an intercostal catheter placed in the empty hemithorax to induce
      mediastinal shift and hyperinflation of the left lung without adverse hemodynamic
      sequelae. In experiment 2, 27 sheep were randomly allocated into 3 equal groups
      regarding management of the residual empty right hemithorax: balanced drainage,
      no intercostal drainage, and clamp-release intercostal underwater drainage. A
      fourth group of 9 sheep served as a sham controls placebo with the same
      anesthetic and a right thoracotomy. RESULTS: All sheep tolerated surgery without
      adverse event. In experiment 1, there was significant mediastinal shift at
      necropsy in all sheep and 60% (n = 6) had postpneumonectomy pulmonary edema
      develop in the left lung (P = .023 vs sham). In experiment 2, incidences of
      postpneumonectomy pulmonary edema were as follows: 0 in balanced group (P = .057
      vs other groups), 3 (30%) in no-drainage group, and 3 (30%) in clamp-release
      group. Only the 12 sheep with postpneumonectomy pulmonary edema had respiratory
      distress; the rest had uneventful recoveries. CONCLUSION: In a sheep model of
      postpneumonectomy pulmonary edema, hyperinflation from mediastinal shift is an
      etiologic factor. A balanced drainage system averts postpneumonectomy pulmonary
      edema. This is the first time such a causal relationship has been demonstrated,
      supporting our continued use of balanced drainage after pneumonectomy.

PMID- 17532938
TI  - Associations among bronchioloalveolar carcinoma components, positron emission
      tomographic and computed tomographic findings, and malignant behavior in small
      lung adenocarcinomas.
AB  - OBJECTIVE: The aggressiveness of small adenocarcinomas has not been fully
      evaluated using integrated positron emission tomography/computed tomography. We
      investigated malignant aggressiveness according to positron emission
      tomography/computed tomography, high-resolution computed tomographic findings,
      and the proportions of pathologically defined bronchioloalveolar carcinomas in
      cT1N0M0 lung adenocarcinoma. METHODS: Sixty consecutive patients with cT1N0M0
      lung adenocarcinomas of 3 cm or less in diameter underwent fluorodeoxyglucose
      positron emission tomograph/computed tomography, and high-resolution computed
      tomography, followed by complete tumor resection. Correlations between the
      proportion of bronchioloalveolar carcinoma and maximum standardized uptake value
      on positron emission tomographic scan/computed tomographic scan, ground-glass
      opacity, and tumor shadow disappearance rate were investigated and the findings
      were compared with clinicopathologic features. RESULTS: Lymphatic and vascular
      invasion occurred in 18 (30%) and 13 (22%) patients, respectively, whereas hilar
      or mediastinal lymph nodes occurred in 8 patients (13%). Maximum standardized
      uptake value generally seemed the most valuable predictor of lymphatic invasion,
      vascular invasion, and nodal metastasis compared with ground-glass opacity, tumor
      shadow disappearance rate, and bronchioloalveolar carcinoma ratios. Although the
      association was significant between the bronchioloalveolar carcinoma ratio versus
      maximum standardized uptake value, ground-glass opacity ratio, and tumor shadow
      disappearance rate (all P < .0001), maximum standardized uptake value (R2 =
      0.245) was less correlated with the bronchioloalveolar carcinoma ratio than was
      the ground-glass opacity ratio (R2 = 0.554) and tumor shadow disappearance rate
      (R2 = 0.671). CONCLUSIONS: The malignant behavior of small adenocarcinomas with a
      lower maximum standardized uptake value and a greater proportion of ground-glass
      opacity, tumor shadow disappearance rate, and bronchioloalveolar carcinoma was
      less aggressive. Maximum standardized uptake value was a more powerful clinical
      predictor of biologic tumor performance, independent of pathologic
      bronchioloalveolar carcinoma proportion. Preoperative assessment of maximum
      standardized uptake value on positron emission tomographic/computed tomographic
      findings, in addition to the ground-glass opacity ratio and tumor shadow
      disappearance rate on high-resolution computed tomographic scans, might be useful
      to guide treatment strategies for small adenocarcinomas.

PMID- 17532939
TI  - Aortic root reconstruction with a bioprosthetic valved conduit: a consecutive
      series of 275 procedures.
AB  - OBJECTIVE: The study objective was to assess the results of aortic root
      reconstruction using composite conduits with stented bioprosthetic valves.
      METHODS: A review was conducted of 275 patients (202 were male, mean age 69 +/-
      11 years, range 17-88 years) who underwent aortic root replacement using conduits
      constructed intraoperatively from pericardial valves and impregnated Dacron
      grafts between September 1993 and February 2005. There were 151 patients with
      degenerative aneurysms and 63 patients with atherosclerotic aneurysms; 43
      patients had dissections (9 acute type A), 13 patients had endocarditis, and 5
      patients had other pathologic conditions. The ascending aorta alone was replaced
      in 154 patients, a hemiarch reconstruction was performed in 105 patients, and
      extensive arch reconstruction was performed in 16 patients. Hypothermic
      circulatory arrest and an open distal anastomosis were used in 95% of patients.
      RESULTS: Hospital mortality was 17 of 275 patients (6.2%). Four additional
      patients (1.5%) sustained permanent strokes. Among surviving patients, the rate
      of stroke was estimated as 0.85 per 100 patient-years and the rate of significant
      hemorrhage was estimated as 0.3 per 100 patient-years. Reoperation for valve
      failure occurred in only 1 patient 12 years postoperatively. Long-term survival
      in men was similar to that of a normal matched control population, but was
      significantly lower in women (P = .002). CONCLUSIONS: Men who recover
      satisfactorily after reconstruction of the aortic root with a stented
      bioprosthetic valved conduit (6-month survivors) enjoy long-term outcomes
      equivalent to that of a normal matched population; the postoperative mortality
      rate in women is twice that of a normal population.

PMID- 17532940
TI  - The impact of patient-prosthesis mismatch on late outcomes after mitral valve
      replacement.
AB  - OBJECTIVES: The incidence of patient-prosthesis mismatch after mitral valve
      replacement and its effect on late outcomes have remained unclear. This study was
      conducted to determine the impact of patient-prosthesis mismatch on recurrent
      congestive heart failure, postoperative pulmonary hypertension, and late survival
      after mitral valve replacement. METHODS: Between 1985 and 2005, 884 patients,
      with a mean age 63 +/- 12 years, underwent mitral valve replacement (657
      mechanical, 227 bioprosthesis) with contemporary prostheses. Mean clinical and
      echocardiographic follow-up was 5.1 +/- 4.1 years (4344 patient-years). Patient
      prosthesis mismatch was defined as an indexed effective orifice area of 1.25
      cm2/m2 or less. Parametric and nonparametric analyses were used to determine
      predictors of outcomes. RESULTS: The incidence of patient-prosthesis mismatch was
      32%. Predictors of recurrent congestive heart failure included low indexed
      effective orifice area, low ejection fraction, elevated postoperative mean mitral
      gradient, and use of a bioprosthesis (P < or = .05). Postoperative pulmonary
      hypertension was associated with small mitral size, elevated mean mitral
      gradient, low ejection fraction, and atrial fibrillation (P < or = .05); indexed
      effective orifice area did not predict postoperative pulmonary hypertension (P =
      .89). Poor late survival was predicted by low indexed effective orifice area (<
      or =1.25 cm2/m2), New York Heart Association class 3 or 4, elevated right
      ventricular pressure, stroke, older age, coronary artery disease, and
      bioprosthesis use (P < or = .05). Survival for patients with patient-prosthesis
      mismatch versus those without patient-prosthesis mismatch at 1, 3, 5, and 10
      years was 91% versus 95%, 85% versus 90%, 78% versus 86%, and 65% versus 75%,
      respectively (P = .05). CONCLUSIONS: Patient-prosthesis mismatch after mitral
      valve replacement is not uncommon; it is associated with recurrence of congestive
      heart failure and postoperative pulmonary hypertension and independently affected
      late survival. This study emphasizes the importance of implanting a sufficiently
      large prosthesis in adult patients undergoing mitral valve replacement.

PMID- 17532942
TI  - Endovascular treatment of thoracoabdominal aortic aneurysms.
AB  - OBJECTIVE: To establish the safety and efficacy of endovascular repair of
      thoracoabdominal aortic aneurysms. METHODS: Between May 2004 and February 2006,
      patients with thoracoabdominal aneurysms considered high risk for conventional
      surgery were enrolled in a prospective trial to evaluate a novel endovascular
      grafting system. Devices were custom designed for each patient using high
      resolution computed tomography. Patient data included mortality, morbidity,
      procedural details, and surrogate end points for endovascular repair. These were
      collected at hospital discharge and at 1, 6, and 12 months. RESULTS: Seventy
      three patients underwent endovascular repair of thoracoabdominal aortic aneurysms
      for type I, II, or III (n = 28), or for type IV (n = 45) thoracoabdominal
      aneurysms. Mean aneurysm size was 7.1 cm (range 4.5-11.3 cm). General anesthesia
      was used in 47% of patients and regional anesthesia in 53%. There were no
      conversions to open surgery nor ruptures post-treatment. Technical success was
      achieved in 93% of patients (68/73). Thirty-day mortality was 5.5% (4/73). Major
      perioperative complications occurred in 11 (14%) patients and included paraplegia
      (2.7%, 2/73), new onset of dialysis (1.4%, 1/73), prolonged ventilator support
      (6.8%, 5/73), myocardial infarction (5.5%, 4/73), and minor hemorrhagic stroke
      (1.4%; 1/72). A majority of patients had no complications. Mean length of stay
      was 8.6 days. At follow-up, 6 deaths had occurred. There were no instances of
      stent migration nor aneurysmal growth. CONCLUSIONS: Endovascular repair of aortic
      aneurysms involving the visceral segment in nonsurgical candidates is feasible.
      Known complications of repair are not eliminated, but morbidity and mortality
      appeared low relative to the high-risk population studied. Further refinement of
      device design, delivery technique, and patient selection is ongoing. Assessment
      of durability will require longer follow-up.

PMID- 17532944
TI  - Initial results of the chordal-cutting operation for ischemic mitral
      regurgitation.
AB  - OBJECTIVE: Division of secondary chords (chordal cutting) has been proposed as a
      method for decreasing mitral valve leaflet tethering and mitral regurgitation in
      patients with ischemic mitral regurgitation. However, very little clinical data
      exist to date for this procedure. METHODS: We compared echocardiographic and
      clinical data in patients who underwent chordal-cutting mitral valve repair (n =
      43) and those undergoing conventional mitral valve repair (control, n = 49) for
      ischemic mitral regurgitation. RESULTS: Patients who underwent chordal cutting
      had a higher prevalence of recent myocardial infarction, left main disease,
      diabetes, and peripheral vascular disease (all P < .05). Left ventricular
      ejection fraction was lower in the chordal-cutting group (33 +/- 2% vs 44 +/- 2%)
      (mean +/- SE) and preoperative tent height was greater (11.7 +/- 0.5 vs 9.7 +/-
      0.6 mm; both P < .01). In-hospital mortality was 10% in control patients and 9%
      in the chordal-cutting group (P = .9). Other complication rates were similar for
      the two groups. The reduction in tent height before-to-after repair was similar
      in the two groups of patients, but those undergoing chordal cutting had a greater
      reductions in tent area (53 +/- 3% vs 41 +/- 3%; P = .01). The chordal-cutting
      group also had greater mobility of the anterior leaflet, as measured by a
      reduction in the distance between the free edge of the anterior mitral valve
      leaflet and the posterior left ventricular wall (24 +/- 3% vs 11 +/- 4%; P =
      .01). Control patients had more recurrent mitral regurgitation during 2 years of
      follow-up by univariate (37% vs 15%; P = .03) and multivariate analysis (P =
      .03). Chordal cutting did not adversely affect postoperative left ventricular
      ejection fraction (10% +/- 5% relative increase in left ventricular ejection
      fraction vs 11% +/- 6% in the control group; P = .9). CONCLUSION: Chordal cutting
      improves mitral valve leaflet mobility and reduces mitral regurgitation
      recurrence in patients with ischemic mitral regurgitation, without any obvious
      deleterious effects on left ventricular function.

PMID- 17532946
TI  - Analysis of the postoperative epicardial auriculogram after surgical ablation of
      atrial fibrillation: risk stratification of late recurrences.
AB  - OBJECTIVES: Late recurrence of atrial fibrillation frequently occurs after atrial
      ablation. Risk stratification for success and recurrence of the antiarrhythmic
      surgical procedure has not yet been established. We studied postoperative
      epicardial unipolar auriculograms to distinguish between high- and low-risk
      patients with late recurrence of atrial fibrillation. METHODS: Epicardial atrial
      fibrillatory activity was registered in 70 patients with surgical ablation of
      permanent atrial fibrillation and postoperative recurrence through the temporary
      wires. The atrial activation pattern was characterized in 3 groups (type I, II,
      and III) using Wells's criteria. The groups were homogeneous in the main clinical
      preoperative and surgical variables. RESULTS: Mean atrial frequency of
      postoperative atrial fibrillation recurrence showed differences between groups:
      225 +/- 53 ms in type I, 177 +/- 21 ms in type II, and 150 +/- 19 ms in type III
      (P < .01). At the end of the study, sinus rhythm was achieved in 80% of the
      subjects with type I, 87.5% with type II, and 23.8% with type III (P < .001).
      During follow-up, late atrial fibrillation recurred in 21.7% of patients with
      type I, 17.4% with type II, and 64.2% with auriculogram type III. In multivariate
      regression analysis, the postoperative auriculogram type III was the only
      predictor of late atrial fibrillation recurrence (odds ratio 15.6; 95% confidence
      interval, 3.2-74.7; P < .001). CONCLUSIONS: The unipolar epicardial auriculogram
      was able to characterize the complexity of the postoperative fibrillatory process
      and also to identify patients with a high risk of late recurrence. Auriculogram
      type III had a low success rate for the intraoperative ablation procedure. The
      lines of the ablation procedure facilitated organization of the auriculograms.

PMID- 17532947
TI  - Off-pump bypass of the left anterior descending coronary artery: 23- to 34-year
      follow-up.
AB  - OBJECTIVE: We sought to develop a baseline for long-term survival of patients
      after off-pump bypass of the left anterior descending coronary artery with the
      heart beating. METHODS: We reviewed results for 241 consecutive patients with
      significant obstruction of the left anterior descending coronary artery who
      underwent surgery between November 1969 and the end of 1980. The off-pump
      operative technique involved elevating and stabilizing a segment of the distal
      left anterior descending coronary artery with 4 traction sutures. Starting in
      1973, an internal thoracic artery became the graft of choice, so that a total of
      171 patients received an internal thoracic artery bypass graft, and 70 patients
      received a saphenous vein graft. RESULTS: The median survival of patients with
      internal thoracic artery grafts was 23.7 years versus 17.9 years for patients
      with venous grafts (P < .02). Early patency of arterial grafts was 95%, and late
      patency was 90%. There were 2 (0.8%) operative deaths. Seventy of the 74 patients
      still alive in 2003 were interviewed by telephone, and 40 (57%) did not require
      additional invasive treatment, which is consistent with our finding that more
      than 50% of our patients after bypass of the left anterior descending coronary
      remained stable without obstruction of the right or circumflex arteries. However,
      atherosclerosis progressed in 30 (43%) of the survivors, who underwent
      reinterventions. CONCLUSIONS: Off-pump bypass of the left anterior descending
      coronary artery with an internal thoracic artery can be done on a beating heart
      safely and results in median survival of patients for more than 23 years.

PMID- 17532948
TI  - Intermediate-term results of ascending-descending posterior pericardial bypass of
      complex aortic coarctation.
AB  - OBJECTIVE: Extra-anatomic bypass of complex thoracic aortic disease through a
      median sternotomy has been reported as a safe alternative to thoracotomy. Our
      objective was to examine intermediate-term outcomes. METHODS: We retrospectively
      reviewed 50 consecutive patients with congenital aortic coarctation or recurrent
      coarctation who underwent ascending-descending posterior pericardial aortic
      bypass between January 1985 and November 2005. Demographic data, in-hospital and
      postoperative morbidity and mortality, and resolution of hypertension were
      determined by examination of the medical record. RESULTS: The mean age at
      operation was 42 years; 27 (54%) were men. There were no perioperative deaths.
      Upper-extremity blood pressure after coarctation repair with ascending-descending
      aortic bypass was significantly improved. Mean systolic blood pressure decreased
      from 158 +/- 25 mm Hg preoperatively to 123 +/- 14 mm Hg postoperatively (P <
      .001). There were no graft-related deaths or complications in follow-up extending
      up to 20 years. CONCLUSIONS: The ascending-descending aortic bypass through a
      posterior pericardial approach is a safe operation and is effective in relieving
      obstruction and improving hypertension.

PMID- 17532949
TI  - Reversible pulmonary trunk banding III: assessment of myocardial adaptive
      mechanisms-contribution of cell proliferation.
AB  - OBJECTIVES: Rapid ventricular conditioning induced by pulmonary artery banding
      has been recommended for patients with transposition of the great arteries who
      have lost the chance for the arterial switch operation or whose systemic (right)
      ventricle failed after the atrial switch. The present study was designed to
      experimentally evaluate 2 types of pulmonary artery banding (continuous and
      intermittent) and verify histologically the changes (hypertrophy or hyperplasia
      or both) of cardiomyocytes and vascular and interstitial cells from the
      stimulated ventricle beyond the neonatal period. METHODS: Twenty-one goats, 30 to
      60 days old, were divided into 3 groups, each comprising 7 animals, as follows:
      control group (no surgical procedure); continuously stimulated group (systolic
      overload maintained for 96 hours); and intermittently stimulated group (4 periods
      of 12-hour systolic overload, alternated with a resting period of 12 hours). The
      animals were then killed for histologic and immunohistochemical analysis of the
      hearts. Murine monoclonal antibody Ki-67 was used as a proliferation cell marker.
      Myocardial collagen area fraction was determined by Sirius red staining. RESULTS:
      For both stimulated groups, a significant increase occurred in right ventricular
      cardiomyocytes and respective nuclei diameters compared with the controls (P <
      .05). The number of Ki-67-positive cardiomyocytes and interstitial/vessel cells
      from the right ventricle was augmented in both trained groups in relation to the
      left ventricle (P < .05). There was no significant difference in the right
      ventricular collagen area fraction from both trained groups compared with
      controls. CONCLUSIONS: Irrespective of the shorter training time (periods of
      overload intercalated with resting), the intermittent stimulation regimen was
      able to produce a similar training of the subpulmonary ventricle compared with
      the continuous stimulation regarding mass acquisition, cell hypertrophy, and
      hyperplasia.

PMID- 17532950
TI  - Failure of prophylactic intravenous immunoglobulin to prevent sensitization to
      cryopreserved allograft tissue used in congenital cardiac surgery.
AB  - OBJECTIVE: Cryopreserved allograft tissue used in the Norwood procedure for
      infants with hypoplastic left heart syndrome causes profound immunologic
      sensitization, which may complicate future transplantation. Intravenous
      immunoglobulin has been shown to reduce sensitization after it has developed,
      allowing successful transplantation. The purpose of this pilot trial was to
      determine whether intravenous immunoglobulin given before and after the procedure
      could prevent sensitization to cryopreserved allograft patches used in the
      initial repair of hypoplastic left heart syndrome. METHODS: Intravenous
      immunoglobulin (2 g/kg) was given preoperatively, 3 weeks postoperatively, and 4
      months postoperatively to 7 infants undergoing the Norwood procedure. Panel
      reactive antibodies were measured with flow cytometry preoperatively and at 1, 4,
      6, and 12 months postoperatively and compared with values from a contemporary
      cohort of 12 infants undergoing the Norwood procedure who did not receive
      intravenous immunoglobulin. RESULTS: The groups were well matched for length and
      weight at time of surgery. Control infants were somewhat younger than the cohort
      receiving intravenous immunoglobulin (8 +/- 5 vs 17 +/- 14 days, P = .021). There
      were no differences in transfusion requirements. There was no difference in the
      degree of sensitization between control and intravenous immunoglobulin groups at
      1 month (class I panel-reactive antibodies 20% +/- 30% vs 4% +/- 9%, P = .443,
      class II panel-reactive antibodies 17% +/- 27% vs 20% +/- 17%, P = .400), 4
      months (class I panel-reactive antibodies 62% +/- 40% vs 73% +/- 41%, P = .813,
      class II panel-reactive antibodies 49% +/- 42% vs 54% +/- 41%, P = .706), and 12
      months (class I panel-reactive antibodies 49% +/- 42% vs 58% +/- 39%, P = .686,
      class II panel-reactive antibodies 44% +/- 36% vs 49% +/- 42%, P = .651).
      CONCLUSION: Despite studies showing intravenous immunoglobulin to reduce
      sensitization, we were unable to demonstrate that intravenous immunoglobulin
      prevented sensitization after exposure to allograft tissue in neonates undergoing
      congenital cardiac surgery.

PMID- 17532951
TI  - Neurodevelopmental and neuroradiologic outcomes in patients with univentricular
      heart aged 5 to 7 years: related risk factor analysis.
AB  - OBJECTIVE: Despite improved survival and neurodevelopmental outcome, children
      with hypoplastic left heart syndrome and other forms of univentricular heart
      remain at increased risk for cognitive, motor, and other neurologic deficits.
      METHODS: We examined 27 children with hypoplastic left heart syndrome or other
      forms of univentricular heart at a median age of 5.70 years (range 4.99-7.51
      years) and performed brain computed tomography or magnetic resonance imaging on
      20. Possible risk factors were correlated with outcome. RESULTS: Mean full-scale
      IQ among patients with hypoplastic left heart syndrome was 86.7; that among
      patients with other forms of univentricular heart was 89.1, with both differing
      significantly from the expected population mean (P = .015 and P = .029,
      respectively). Cerebral palsy was diagnosed in 1 of 7 patients with hypoplastic
      left heart syndrome and 2 of 20 with other forms of univentricular heart. Brain
      computed tomography or magnetic resonance imaging revealed ischemic changes and
      infarcts or atrophy in 5 of 8 patients who had undergone the Norwood procedure
      and in 2 of 12 of those who had not (P = .062). Abnormal computed tomographic
      findings correlated significantly with lower full-scale IQ (P = .045) and verbal
      IQ (P = .02). In the multiple linear regression model, diuresis the third day
      after the primary operation and cardiopulmonary bypass time in the bidirectional
      Glenn operation correlated significantly with the primary outcome of full-scale
      IQ. CONCLUSION: In children with univentricular heart, intellectual and
      neurologic deficits are common. Perioperative and postoperative risk factors
      related to the primary phase and bidirectional Glenn operation contribute to
      these deficits.

PMID- 17532952
TI  - Late cardiopulmonary and musculoskeletal exercise performance after repair for
      total anomalous pulmonary venous connection during infancy.
AB  - OBJECTIVES: We evaluated cardiopulmonary function at rest and during exercise in
      children after surgical repair for total anomalous pulmonary venous connection.
      BACKGROUND: Long-term assessment of cardiopulmonary function during exercise in
      children after repair for total anomalous pulmonary venous connection during
      infancy is limited. METHODS: Resting lung function and cardiopulmonary function
      during maximal ramp cycle ergometry were evaluated in 27 patients (age = 11 +/- 4
      years, 20 were male). Peak oxygen consumption, ventilatory anaerobic threshold,
      and physical working capacity were compared with normal reference values.
      Neurologic assessment included neuromuscular function, inattentiveness, and
      hyperactivity. Patient- and procedure-related variables were assessed for
      association with peak oxygen consumption, ventilatory anaerobic threshold, and
      physical working capacity. RESULTS: Compared with healthy children, peak oxygen
      consumption (88% +/- 16% of predicted) and ventilatory anaerobic threshold (91%
      +/- 21% of predicted) were mildly reduced. Chronotropic impairment was observed
      in 7 patients (32%). Patients with impaired resting lung mechanics were more
      likely to have impairment in peak oxygen consumption (P < .05). Breathing reserve
      was normal. Specific anatomy and all operative factors did not have a significant
      impact on overall exercise performance. Composite score for fine and gross motor
      function was associated with lower ventilatory anaerobic threshold (P < .05).
      CONCLUSIONS: Exercise performance is mildly impaired at long-term follow-up after
      total anomalous pulmonary venous connection repair during infancy. Residual
      pulmonary abnormalities are common and associated with lower exercise
      performance. Neurologic abnormalities are evident in a subgroup, but the impact
      on late exercise performance is inconclusive.

PMID- 17532953
TI  - Coarctectomy reduces neoaortic arch obstruction in hypoplastic left heart
      syndrome.
AB  - OBJECTIVE: Neoaortic arch obstruction after stage I palliation is an important
      risk factor affecting interstage mortality in patients with hypoplastic left
      heart syndrome, with no accepted standard surgical approach. We sought to
      determine the efficacy of different techniques for aortic arch reconstruction to
      reduce the incidence of postoperative neoaortic arch obstruction. METHODS: From
      January 2000 through June 2005, 210 patients underwent stage I palliation. To
      enlarge the aortic arch, 12 (6%) patients had a direct connection, 115 (55%)
      patients had an aortic homograft, 53 (25%) patients had a pulmonary homograft
      patch, and 30 (14%) patients had autologous pericardium. Independent of the
      technique for aortic enlargement, 55 (26%) children had coarctectomy. RESULTS:
      Eighty patients had a significant arch gradient, as determined by means of
      echocardiography, and of these, 50 required balloon angioplasty, surgical arch
      augmentation, or both. Preoperative aortic coarctation was consistently linked to
      neoaortic arch obstruction (P = .032). Patients having aortic arch enlargement by
      means of direct connection or with autologous pericardium were less likely to
      have neoaortic arch obstruction (P = .049). Coarctectomy resulted in a lower
      incidence of neoaortic arch obstruction, as determined by means of
      echocardiography (P = .015), or need for reintervention (P = .01). CONCLUSIONS:
      Patients with hypoplastic left heart syndrome undergoing aortic arch enlargement
      with autologous tissue are less likely to require intervention for neoaortic arch
      obstruction compared with those having homograft patch reconstruction. Excision
      of all ductal tissue by means of coarctectomy reduces the risk of recurrent
      aortic arch obstruction. An aggressive approach to reconstruction of the arch and
      the use of autologous tissue at the time of stage I palliation is advocated.

PMID- 17532955
TI  - Evaluating the safety implications of aprotinin use: the Retrospective Evaluation
      of Aprotinin in Cardio Thoracic Surgery (REACTS).
AB  - OBJECTIVES: Aprotinin is a drug used to reduce bleeding in patients undergoing
      cardiothoracic surgery with cardiopulmonary bypass. A recent cohort evaluation
      found elevated risks of renal, cardiovascular, and cerebrovascular events when
      aprotinin was used. We sought to determine the impact of aprotinin on safety
      variables among patients receiving cardiothoracic surgery with cardiopulmonary
      bypass from a single US hospital that reserves aprotinin for complex surgeries
      and Jehovah's Witnesses and does not utilize celite-based activated clotting time
      determinations. METHODS: We performed a cohort evaluation with multivariate
      logistic regression, including propensity score adjustment comprising patients
      from January 1, 2000 and December 31, 2005. We evaluated 3348 patients having
      cardiothoracic surgery in a single tertiary care medical center. We observed
      aprotinin use or lack of aprotinin in cardiothoracic surgery. The main outcome
      measures were odds (expressed as an odds ratio with 95% confidence interval) of
      developing myocardial infarction, cerebrovascular events, and renal dysfunction
      after cardiothoracic surgery between groups. RESULTS: Patients receiving
      aprotinin were less likely to experience a cerebrovascular event compared with
      control [0.65 (0.46-0.91)] and did not have an elevated odds of myocardial
      infarction [1.04 (0.53-2.04)] but were more likely to experience postoperative
      renal dysfunction [2.03 (1.37-3.01)]. CONCLUSIONS: Aprotinin was not associated
      with negative myocardial or cerebrovascular risks but did increase the risk of
      renal dysfunction. It is not known whether the renal dysfunction reflects renal
      damage or a transient reduction in glomerular filtration pressure.

PMID- 17532956
TI  - The adverse effect of back-bleeding from lumbar arteries on spinal cord
      pathophysiology in a rabbit model.
AB  - OBJECTIVE: The purpose of this study was to evaluate the adverse effect of back
      bleeding from the lumbar arteries on spinal cord pathophysiology in a rabbit
      model. METHODS: White rabbits were divided into 3 groups. Through laparotomy, the
      abdominal aorta was clamped below the renal artery and above the aortic
      bifurcation for 15 minutes. In group 1 (n = 13), back-bleeding from the lumbar
      arteries was drained from the aorta during aortic clamping. In group 2 (n = 10),
      back-bleeding was not drained. Group 3 (n = 6) was the sham-operated group.
      Postoperative hind limb function was evaluated using the modified Tarlov scale,
      and cell damage was analyzed by counting the number of intact motor neurons and
      terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end
      labeling (TUNEL)-positive neurons. RESULTS: At 4 hours after operation, all
      animals were neurologically impaired in group 1 and normal in group 2. Motor
      neurons were significantly damaged in group 1 compared with groups 2 and 3 (P <
      .05). Forty-eight hours later, almost all animals were neurologically and
      pathologically damaged in groups 1 and 2. There was no difference in the number
      of normal motor neurons between the two groups, but the number of TUNEL-positive
      cells in group 2 was significantly larger than those in group 1. CONCLUSIONS:
      Rabbits with 15-minute aortic clamping in the infrarenal portion showed delayed
      paraplegia, and those with back-bleeding from lumbar arteries showed early onset
      of paraplegia. The prevention of back-bleeding from intercostal arteries and
      lumbar arteries during thoracoabdominal aortic surgery was considered to reduce
      spinal ischemic injury.

PMID- 17532957
TI  - Reliability of temperatures measured at standard monitoring sites as an index of
      brain temperature during deep hypothermic cardiopulmonary bypass conducted for
      thoracic aortic reconstruction.
AB  - OBJECTIVE: It is essential to estimate the brain temperature of patients during
      deliberate deep hypothermia. Using jugular bulb temperature as a standard for
      brain temperature, we evaluated the accuracy and precision of 5 standard
      temperature monitoring sites (ie, pulmonary artery, nasopharynx, forehead deep
      tissue, urinary bladder, and fingertip skin-surface tissue) during deep
      hypothermic cardiopulmonary bypass conducted for thoracic aortic reconstruction.
      METHODS: In 20 adult patients with thoracic aortic aneurysms, the 5 temperature
      monitoring sites were recorded every 1 minute during deep hypothermic (<20
      degrees C) cardiopulmonary bypass. The accuracy was evaluated by the difference
      from jugular bulb temperature, and the precision was evaluated by its standard
      deviation, as well as by the correlation with jugular bulb temperature. RESULTS:
      Pulmonary artery temperature and jugular bulb temperature began to change
      immediately after the start of cooling or rewarming, closely matching each other,
      and the other temperatures lagged behind these two temperatures. During either
      situation, the accuracy of pulmonary artery temperature measurement (0.3 degrees
      C-0.5 degrees C) was much superior to the other measurements, and its precision
      (standard deviation of the difference from jugular bulb temperature = 1.5 degrees
      C-1.8 degrees C; correlation coefficient = 0.94-0.95) was also best among the
      measurements, with its rank order being pulmonary artery > or = nasopharynx >
      forehead > bladder > fingertip. However, the accuracy and precision of pulmonary
      artery temperature measurement was significantly impaired during and for several
      minutes after infusion of cold cardioplegic solution. CONCLUSIONS: Pulmonary
      artery temperature measurement is recommended to estimate brain temperature
      during deep hypothermic cardiopulmonary bypass, even if it is conducted with the
      sternum opened; however, caution needs to be exercised in interpreting its
      measurements during periods of the cardioplegic solution infusion.

PMID- 17532958
TI  - Patients with diabetes mellitus undergoing cardiac surgery are at greater risk
      for developing intraoperative myocardial acidosis.
AB  - OBJECTIVE: In patients undergoing cardiac surgery, intraoperative myocardial
      acidosis, which quantifies regional myocardial ischemia, has been shown to
      increase the risk of adverse postoperative outcomes. In this study, we sought to
      determine the course of intraoperative myocardial acidosis and its impact on
      postoperative survival in patients with diabetes mellitus undergoing cardiac
      surgery. METHODS: Intraoperative myocardial tissue pH(37C) was continuously
      measured in the anterior and posterior left ventricular walls in 264 patients
      undergoing cardiac surgery; 74 (28.0%) of the patients had diabetes (insulin
      dependent diabetes: 54%; non-insulin dependent diabetes: 46%). The shortest time
      required to reach intraoperative myocardial tissue pH < 6.34 during aortic
      occlusion and > 6.73 during reperfusion were compared in 3 patient groups:
      insulin-dependent, non-insulin dependent, and nondiabetic. These pH thresholds
      have been demonstrated to be associated with adverse postoperative long-term
      survival. RESULTS: The median times to reach intraoperative myocardial tissue
      pH(37C) < 6.34 during aortic occlusion were 14, 23, and 36 minutes in the insulin
      dependent, non-insulin dependent, and non-diabetic groups, respectively (P =
      .003). The time taken to reach intraoperative myocardial tissue pH(37C) > 6.73
      during reperfusion was similar between the 3 groups. After adjusting for relevant
      pre- and intraoperative parameters, the risk of developing intraoperative
      myocardial tissue pH < 6.34 during aortic occlusion was 73% higher in patients
      with insulin-dependent diabetes mellitus (P = .022) but the same in with patients
      with non-insulin dependent diabetes mellitus (P = .98) when compared with
      patients without diabetes. Patients with insulin-dependent diabetes mellitus also
      had nearly threefold decrease in long-term survival compared with that of
      patients without diabetes (P = .0007). CONCLUSIONS: Patients with insulin
      dependent diabetes mellitus undergoing cardiac surgery are at a greater risk of
      developing intraoperative myocardial acidosis/ischemia and of decreased survival
      postoperatively compared with patients without diabetes.

PMID- 17532959
TI  - Results of a multicenter clinical trial with the Thoratec Implantable Ventricular
      Assist Device.
AB  - OBJECTIVE: The Thoratec Implantable Ventricular Assist Device (Thoratec
      Corporation, Pleasanton, Calif) can be used for univentricular or biventricular
      support in patients with a body surface area as low as 1.3 m(2). Results of the
      multicenter clinical trial are reviewed. METHODS: Between October 2001 and June
      2004, a total of 39 patients at 12 institutions were supported with the Thoratec
      Implantable Ventricular Assist Device. Twenty-four patients (62%) received left
      ventricular assist devices and 15 (38%) received biventricular assist devices.
      Indications included bridge to transplantation (n = 30) and postcardiotomy
      failure (n = 9). The control group included 100 patients from the Food and Drug
      Administration approval submissions for the paracorporeal version of the
      ventricular assist device. RESULTS: Twenty-eight male and 11 female patients,
      with mean age of 48 years (16-71 years) and body surface area of 1.9 m(2) (1.3
      2.4 m2) were supported for 3938 patient-days (10.8 patient-years). Mean left
      ventricular assist device flow index on the first postoperative day was 2.5 +/-
      0.5 L/(min x m2). Mean duration of support was 101 days (9-597 days). Eighteen
      patients were discharged after a mean duration of 96 days. There were no
      ventricular assist device failures. Complications included 13 cases of bleeding
      requiring reexploration (33.3%), 1 embolic and 2 hemorrhagic strokes (7.7%), 5
      driveline infections (12.8%), and 2 pocket infections (5%). Support to successful
      outcomes was 70% for bridge to transplantation and 67% for postcardiotomy
      recovery, versus historical results for the paracorporeal ventricular assist
      device of 69% for bridge to transplantation and 48% for postcardiotomy recovery.
      CONCLUSION: The Thoratec Implantable Ventricular Assist Device is a new
      implantable pulsatile ventricular assist device that allows hospital discharge
      for patients as a bridge to transplantation or for postcardiotomy failure. It is
      the first Food and Drug Administration-approved implantable ventricular assist
      device with biventricular capability.

PMID- 17532960
TI  - Beck and back: a paradigm change in coronary sinus interventions--pulsatile
      stretch on intact coronary venous endothelium.
AB  - OBJECTIVES: Strategies to recover myocardium in therapeutically unresponsive
      patients are again under scrutiny, including techniques developed in the
      pioneering days of cardiothoracic surgery such as retroperfusion via the coronary
      sinus--the Beck procedure. An underestimated aspect of retroperfusion is the
      formation of new vessels. This early observation of neoangiogenesis may be an
      important mechanism in observed benefits. We hypothesized that periodic pressure
      elevation in coronary veins induces an analogy to shear stress angiogenic pulses
      by activating venous endothelium. Pulsatile stretch on venous endothelium can be
      achieved easily by a pressure-controlled intermittent balloon blockade of the
      coronary sinus outflow. METHODS: Three hours of myocardial ischemia was induced
      in 12 pigs. Pressure-controlled intermittent coronary sinus occlusion was applied
      in 6 animals 15 minutes after occlusion of the left anterior descending coronary
      artery. Postmortem myocardial specimens were taken, and heme oxygenase-1,
      vascular endothelial growth factor gene expression, and hypoxia-induced factor
      activity were measured. RESULTS: As compared with controls, treated animals
      released an angiogenic pulse by a 4-fold increase of heme oxygenase-1 gene
      expression in the infarct area (P < .001), together with a 2.5-fold enhanced
      transcription of vascular endothelial growth factor in the infarct (P < .006),
      border (P < .002), and remote (P < .02) areas, whereas hypoxia-induced factor
      activity was similar in both groups. A significant correlation (P < .01) of the
      achieved coronary sinus pressure elevation and gene expression was found.
      CONCLUSIONS: Mechanotransduction of pulsatile stretch on coronary venous
      endothelium by pressure-controlled intermittent coronary sinus occlusion induces
      heme oxygenase-1 and vascular endothelial growth factor gene expression, leaving
      the ischemic pathway of the hypoxia-induced factor activity unchanged. This
      cascade of molecular events closes the argument gap to historical reports of the
      Beck procedure on revascularization and myocardial salvage.

PMID- 17532961
TI  - Lipopolysaccharide preconditioning induces robust protection against brain injury
      resulting from deep hypothermic circulatory arrest.
AB  - OBJECTIVE: Delayed preconditioning genetically reprograms the response to
      ischemic injury. Subclinical bacterial lipopolysaccharide acts through
      preconditioning, powerfully protecting against experimental stroke. We
      investigated the potential for lipopolysaccharide to protect against brain injury
      related to cardiopulmonary bypass. METHODS: Neonatal piglets were blindly and
      randomly preconditioned with lipopolysaccharide (n = 6) or saline (n = 6). Three
      days later, they experienced 2 hours of deep hypothermic circulatory arrest
      before being weaned and supported anesthetized for 20 hours in an intensive care
      setting. Controls included cardiopulmonary bypass without deep hypothermic
      circulatory arrest (n = 3) and no cardiopulmonary bypass (n = 3). Brain injury
      was quantified by light and fluorescent microscopy (Fluoro-Jade; Histo-Chem, Inc,
      Jefferson, Ark). RESULTS: All animals were clinically indistinguishable before
      surgery. Perioperative and postoperative parameters between experimental groups
      were similar. No control animal scored falsely positive. Histologic scores were
      0.33 +/- 0.21, 0.66 +/- 0.42, and 0.5 +/- 0.24 in the cortex, basal ganglia, and
      hippocampus, respectively, in the lipopolysaccharide-treated animals but
      significantly worse in all saline control animals (1.33 +/- 0.21, P < .01; 1.66
      +/- 0.33, P = .09; and 6.0 +/- 1.5, P < .01). One lipopolysaccharide-treated
      brain was histologically indistinguishable from controls. CONCLUSION: This is the
      first evidence that lipopolysaccharide can precondition against cardiopulmonary
      bypass-related injury. Because lipopolysaccharide preconditioning is a systemic
      phenomenon offering proven protection against myocardial, hepatic, and pulmonary
      injury, this technique offers enormous potential for protecting against systemic
      neonatal injury related to cardiopulmonary bypass.

PMID- 17532962
TI  - Antiplatelet therapy in patients receiving aortic bioprostheses: a report of
      clinical and instrumental safety.
AB  - OBJECTIVE: The main advantage of bioprostheses, avoidance of anticoagulant
      therapy, is compromised during the early postoperative period; in fact, warfarin
      is often administered during the first 3 postoperative months. METHODS: We
      analyzed 250 patients undergoing tissue aortic valve replacement between January
      2002 and December 2005. The patients received either aspirin (group 1) or oral
      anticoagulation (group 2) during the first 3 months. In a subgroup of these
      patients, we investigated the possible presence of clinically silent
      microembolization by means of transcranial Doppler for microembolic signal
      detection. RESULTS: Thirty-day mortality was 0%. No major neurologic events
      occurred. Two episodes of bleeding were observed in both groups. Follow-up time
      was 24 +/- 14 months. Overall late mortality rate was 0.8% in group 1 versus 12%
      (mainly cancer related) in group 2. In group 2, 2 deaths were due to major
      ischemic neurologic events; overall, 3 major neurologic episodes occurred
      (international normalized ratio was within therapeutic range). There were no
      neurologic events in group 1 (P = .12). Stroke-free survival did not reach
      statistical significance between the 2 groups. Transcranial Doppler was performed
      after a mean interval of 55 +/- 19 days, with no detection of microembolic
      signals in patients receiving either aspirin or warfarin. There were no episodes
      of bleeding or neurologic events. CONCLUSIONS: Aspirin therapy appears to be the
      appropriate response to both cardiac surgeons' and patients' needs in the early
      postoperative course after aortic valve replacement with tissue valves,
      demonstrating adequate antithromboembolic efficacy with no added risk for
      bleeding as well as ease of administration.

PMID- 17532963
TI  - Effects of pyridoxal-5'-phosphate (MC-1) in patients undergoing high-risk
      coronary artery bypass surgery: results of the MEND-CABG randomized study.
AB  - OBJECTIVE: Coronary artery bypass graft surgery remains associated with
      significant postoperative cardiovascular morbidity and mortality in high-risk
      patients. MC-1 (pyridoxal-5'-phosphate monohydrate) inhibits purinergic receptors
      and intracellular influx of Ca2+, thereby reducing cellular injury during
      experimental ischemia and reperfusion. The MEND-CABG trial tested the hypothesis
      that MC-1 reduces cardiovascular morbidity and mortality after coronary artery
      bypass graft. METHODS: In a phase 2, double-blinded, placebo-controlled study,
      901 patients scheduled for coronary artery bypass graft surgery with
      cardiopulmonary bypass and at high risk for subsequent cardiac or neurologic
      complications were randomly assigned to receive oral MC-1 (250 mg or 750 mg/d
      once daily) or placebo beginning 3 to 10 hours prior to surgery and continued to
      postoperative day 30. RESULTS: At 30 days, MC-1 250 mg (compared with placebo)
      reduced the composite of death, nonfatal cerebral infarction, and nonfatal
      myocardial infarction by 14.0% (P = .3124) with peak creatinine kinase-myocardial
      band > or =50 ng/mL (prespecified primary end point); 32.3% (P = .0349) with peak
      creatinine kinase-myocardial band > or =70 ng/mL; and 37.2% (P = .0283) with peak
      creatinine kinase-myocardial band > or =100 ng/mL. Myocardial infarctions with
      peak creatinine kinase-myocardial band> or =100 ng/mL were reduced by 47.2% in
      the MC-1 250-mg group versus placebo (P = .0083). Greater efficacy was
      demonstrated with 250 mg than with the 750-mg dose of MC-1. CONCLUSIONS: In high
      risk patients undergoing coronary artery bypass graft, treatment with MC-1 did
      not significantly affect the prespecified primary end point but was associated
      with a significant reduction in perioperative myocardial infarction with
      creatinine kinase-myocardial band > or =100 ng/mL. A larger, well-powered trial
      is needed to evaluate the cardioprotective effects of MC-1.

PMID- 17532964
TI  - Prevalence and risks of allosensitization in HeartMate left ventricular assist
      device recipients: the impact of leukofiltered cellular blood product
      transfusions.
AB  - OBJECTIVE: Allosensitization of left ventricular assist device recipients has
      been associated with perioperative transfusion of cellular blood products. The
      relative sensitizing contribution of leukofiltered cellular blood products,
      however, remains unclear. We investigated the pattern of sensitization in left
      ventricular assist device recipients in relation to cellular blood product
      transfusions received. METHODS: Seventy-one consecutive nonsensitized recipients
      of the HeartMate left ventricular assist device (Thoratec Corporation,
      Pleasanton, Calif) as a bridge to transplantation were reviewed. Panel-reactive
      HLA antibody levels at consecutive times after device implantation were
      correlated with perioperative cellular blood product transfusions. RESULTS: Fifty
      four patients received leukofiltered cellular blood products (transfused),
      whereas 17 patients received only fresh-frozen plasma (nontransfused). Among
      nontransfused patients, 58.8% (10/17) became sensitized during mechanical
      support, versus 35.2% of transfused patients (19/54, P = .15). There was a trend
      toward more sensitization during the 12 weeks after device placement in
      nontransfused patients. Kaplan-Meier analysis revealed significantly more
      sensitization in nontransfused patients than in transfused patients, despite
      equal rates of transplantation (P = .05). A dose-response analysis revealed
      significant trends toward less sensitization and lower peak panel-reactive
      antibody level with more cellular blood product transfusions (P = .04).
      Multivariate Cox regression revealed only increasing transfusions to be
      associated with a reduced risk of sensitization (hazard ratio 0.18, P = .01).
      CONCLUSIONS: Sensitization becomes more prevalent with increasing length of
      support. Avoidance of perioperative leukocyte-filtered cellular blood product
      transfusions does not decrease the incidence or degree of HLA sensitization.
      Conversely, cellular blood product transfusions may be associated with lessened
      alloimmunization and may mitigate the sensitization seen in recipients of the
      HeartMate left ventricular assist device as a bridge to transplantation.

PMID- 17532965
TI  - Effects of exogenous surfactant instillation in clinical lung transplantation: a
      prospective, randomized trial.
AB  - OBJECTIVE: Despite the introduction of low potassium-based preservation
      strategies for clinical lung transplantation, relevant early graft dysfunction
      occurs in up to 20% of cases after lung transplantation. This was found to be
      frequently associated with postreperfusion surfactant dysfunction. We performed a
      randomized, prospective study investigating the effect of exogenous surfactant
      instillation into human donor lungs on posttransplant surfactant function and on
      clinical outcome. METHODS: Exogenous surfactant was instilled into 15 donor lungs
      before retrieval via bronchoscopy. Bronchoalveolar lavage fluids were taken
      before instillation as well as 24 hours after transplantation. Surfactant
      function, phospholipids, and protein content in bronchoalveolar lavage fluids
      were assessed and clinical data prospectively recorded. Pulmonary function
      testing was performed 4 weeks after lung transplantation. Additionally, the best
      forced expiratory volume in 1 second was determined within the first year after
      lung transplantation. The control group consisted of 14 patients receiving donor
      lungs without surfactant instillation in randomized order. Pulmonary function
      test results were further compared with those of 154 consecutive recipients of
      bilateral lung transplants, which were not involved in the study (historical
      control). RESULTS: No deaths occurred during the first year after lung
      transplantation. Surfactant function in donor lungs was within normal ranges
      before harvest. In the control group, surfactant function was markedly impaired
      after reperfusion. This was significantly improved by surfactant substitution.
      Protein content of the bronchoalveolar lavage fluid in the surfactant group was
      significantly lower, indicating less leakage through the alveolocapillary
      membrane. Forced expiratory volume in 1 second after 4 weeks was significantly
      higher in the surfactant group than in either control group (P = .034 and .01,
      respectively). Interestingly, the best forced expiratory volume in 1 second
      during the first year after lung transplantation was significantly higher in both
      control groups compared with forced expiratory volume measured in examinations 4
      weeks after lung transplantation (P = .01). The best forced expiratory volumes in
      1 second of control patients were comparable with those in surfactant lungs 4
      weeks after transplant. CONCLUSIONS: This study indicates a protective effect of
      exogenous surfactant instillation to donor lungs before retrieval on post-lung
      transplantation surfactant function and on early clinical outcome. This approach
      may help to improve the outcome after lung transplantation in the future.

PMID- 17532966
TI  - Efficacy of MCI-186, a free-radical scavenger and antioxidant, for resuscitation
      of nonbeating donor hearts.
AB  - OBJECTIVE: Oxygen-derived free radicals are responsible in part for reperfusion
      injury in globally ischemic myocardium. In this study, the efficacy for
      resuscitation of nonbeating donor hearts of MCI-186, a free-radical scavenger and
      antioxidant, was investigated in a pig transplantation model. METHODS: Cardiac
      arrest was induced by asphyxiation. After 30 minutes of global ischemia, the
      hearts were excised and immediately reperfused from the aortic root with
      normoxemic blood cardioplegia (PO2 100 mm Hg) for 20 minutes, followed by
      perfusion with hyperoxemic blood (PO2 300 mm Hg). MCI-186 (3 mg/kg) was
      administered into the aortic root for the first 30 minutes of reperfusion in the
      treated group (n = 6), and untreated hearts were used as a control group (n = 6).
      Transplantation was performed with the heart beating. RESULTS:
      Posttransplantation recovery of cardiac output, end-systolic pressure-volume
      ratio, and first derivative of pressure of the left ventricle in the treated
      group were significantly better than those in the control group. The coronary
      sinus-aortic root difference in malondialdehyde levels remained low throughout
      reperfusion in the treated group but abruptly increased after initiation of
      oxygenated blood perfusion in the control group. The MCI-186-treated hearts
      showed low degree of edema and well-preserved ultrastructure with normal
      appearing organelles, whereas the untreated hearts had marked swelling of
      mitochondria and scant glycogen granules. CONCLUSION: MCI-186 exerts a
      cardioprotective action at least partly by inhibition of lipid peroxidation.
      Antioxidant therapy at the initial reperfusion is essential to successful
      resuscitation of nonbeating hearts by continuous myocardial perfusion.

PMID- 17532967
TI  - Reducing the posterior wall length by using a small endoventricular patch for
      ischemic mitral regurgitation.

PMID- 17532968
TI  - The intraoperative "ink test": a novel assessment tool in mitral valve repair.

PMID- 17532969
TI  - Mild hypothermic (30 degrees C) body perfusion during replacement of the aortic
      arch with a novel arterial perfusion cannula.

PMID- 17532970
TI  - Alternative approach for stent grafting of the thoracic descending aorta: the
      antegrade right axillary approach.

PMID- 17532972
TI  - Bleeding sarcoma of the aorta mimicking a symptomatic aneurysm.

PMID- 17532971
TI  - Surgical treatment of tracheoinnominate fistula after stent-graft implantation.

PMID- 17532973
TI  - Reversing the Ross operation: a new reoperation option for autograft failure.

PMID- 17532974
TI  - Long abdominal aortic stenosis: a rare presentation of Takayasu arteritis treated
      with percutaneous stent implantation.

PMID- 17532975
TI  - Successful management of unremitting spasm of the nongrafted right coronary
      artery after off-pump coronary artery bypass grafting.

PMID- 17532976
TI  - Postoperative ventricular septal hematoma: natural history of two pediatric
      cases.

PMID- 17532977
TI  - Fate of the "opened" arterial duct: Lessons learned from bilateral pulmonary
      artery banding for hypoplastic left heart syndrome under the continuous infusion
      of prostaglandin E1.

PMID- 17532978
TI  - Hybrid procedure for the neonatal management of pulmonary atresia with intact
      ventricular septum.

PMID- 17532979
TI  - Reduced regional right ventricular wall motion after transventricular repair of
      tetralogy of Fallot.

PMID- 17532980
TI  - Cervical ectopic thymoma.

PMID- 17532981
TI  - Bilateral sleeve lobectomy for synchronized bilateral central carcinoid tumor.

PMID- 17532982
TI  - A case of recurrent biliptysis.

PMID- 17532983
TI  - Diffuse lymphangiomatosis: are there any clinical or therapeutic standards?

PMID- 17532984
TI  - Giant cavernous hemangioma of the distal esophagus treated with esophagectomy.

PMID- 17532985
TI  - Primary Ewing sarcoma invading the heart: resection and reconstruction.

PMID- 17532986
TI  - Combined pedicled antropyloroplasty and gastric pull-up reconstruction for
      corrosive esophagogastric stricture.

PMID- 17532987
TI  - Thyroglossal duct cyst within the mediastinum: an extremely unusual location.

PMID- 17532988
TI  - Extracorporeal membrane oxygenation in respiratory failure for pulmonary
      contusion and bronchial disruption after trauma.

PMID- 17532989
TI  - Reduction pneumoplasty for a giant right upper lobe bulla causing massive
      bilateral lung compression.

PMID- 17532990
TI  - Gastropericardial fistula after laparoscopic surgery for gastroesophageal reflux
      disease.

PMID- 17532991
TI  - A pseudoaneurysmal cyst in the pulmonary artery secondary to lung suppuration.

PMID- 17532992
TI  - Extracorporeal membrane oxygenation with direct central cannulation followed by
      delayed chest closure for graft dysfunction after lung transplantation: report of
      two cases with pulmonary arterial hypertension.

PMID- 17532993
TI  - Removable clips for mitral valve repair.

PMID- 17532995
TI  - Intraoperative ablation of atrial fibrillation using bipolar output of surgical
      radiofrequency generator (diathermy) and reusable bipolar forceps.

PMID- 17532996
TI  - Immediate surgery in aortic dissection with cerebral malperfusion.

PMID- 17532997
TI  - High-dose atorvastatin is associated with impaired myocardial angiogenesis in
      response to vascular endothelial growth factor in hypercholesterolemic swine:
      relevance to the human situation?

PMID- 17533000
TI  - Off-pump coronary bypass surgery, graft patency, and the need of an informed
      consent.

PMID- 17533002
TI  - Methicillin-resistant Staphylococcus aureus (MRSA) in foods of animal origin
      product in Italy.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) strains are a global health
      concern. The present study regarded 160 S. aureus strains that had been isolated
      from 1634 foodstuff samples of animal origin in a previous survey conducted in
      Italy during 2003-2005. The strains were characterized by detecting the mecA
      gene, the production of type A to D staphylococcal enterotoxins (SEs), and
      studying their resistance properties against several antibiotics; their
      ecological origin was determined by biotyping. Of the 160 analyzed S. aureus
      strains six (3.75%) were mecA positive and derived from six different samples;
      four isolates were from bovine milk and two from dairy products (pecorino cheese
      and mozzarella cheese). Two strains isolated from milk belonged to the non-host
      specific biovar while the others to the ovine biovar. The strain isolated from
      mozzarella cheese belonged to the non-host-specific biovar and the strain
      isolated from pecorino cheese to the ovine biovar. All the MRSA strains isolated
      were enterotoxigenic; two strains synthesized SEA/SED two SED and one SEC. All
      the strains showed resistance to at least one of the antibiotics tested but none
      was resistant to glycopeptides.

PMID- 17533001
TI  - Speech-associated gestures, Broca's area, and the human mirror system.
AB  - Speech-associated gestures are hand and arm movements that not only convey
      semantic information to listeners but are themselves actions. Broca's area has
      been assumed to play an important role both in semantic retrieval or selection
      (as part of a language comprehension system) and in action recognition (as part
      of a "mirror" or "observation-execution matching" system). We asked whether the
      role that Broca's area plays in processing speech-associated gestures is
      consistent with the semantic retrieval/selection account (predicting relatively
      weak interactions between Broca's area and other cortical areas because the
      meaningful information that speech-associated gestures convey reduces semantic
      ambiguity and thus reduces the need for semantic retrieval/selection) or the
      action recognition account (predicting strong interactions between Broca's area
      and other cortical areas because speech-associated gestures are goal-direct
      actions that are "mirrored"). We compared the functional connectivity of Broca's
      area with other cortical areas when participants listened to stories while
      watching meaningful speech-associated gestures, speech-irrelevant self-grooming
      hand movements, or no hand movements. A network analysis of neuroimaging data
      showed that interactions involving Broca's area and other cortical areas were
      weakest when spoken language was accompanied by meaningful speech-associated
      gestures, and strongest when spoken language was accompanied by self-grooming
      hand movements or by no hand movements at all. Results are discussed with respect
      to the role that the human mirror system plays in processing speech-associated
      movements.

PMID- 17533004
TI  - Inflammatory cells in renal injury and repair.
AB  - Renal inflammation may result from a myriad of insults and often is characterized
      by the presence of infiltrating inflammatory leukocytes within the glomerulus or
      tubulointerstitium. Accumulating evidence indicates that infiltrating leukocytes
      are key players in the induction of renal injury. Although renal inflammation
      often is followed by the development of fibrosis with loss of renal function, it
      can resolve. Resolution may be spontaneous as in poststreptococcal
      glomerulonephritis or after the administration of effective treatment such as
      immunosuppressive agents. The mechanisms and cells underlying the resolution
      process and the exact temporal sequence remains uncertain at present but likely
      involves the removal of injurious leukocytes, the down-regulation of immune
      responses, and the alteration of the phenotype of infiltrating macrophages from
      proinflammatory to prorepair. In this review we examine the role of leukocytes in
      both renal inflammation and repair.

PMID- 17533005
TI  - Role of chemokines for the localization of leukocyte subsets in the kidney.
AB  - Chemokines comprise a family of structurally related chemotactic proteins. They
      bind to about 20 corresponding receptors. Chemokines provide a general
      communication system for cells, and regulate lymphocyte migration under normal
      (homeostatic) and inflammatory conditions. Chemokines organize microenvironments
      in lymphoid tissue, lymphoid organogenesis, and participate in vascular and
      lymphatic angiogenesis. Expressed at the site of injury in the kidney, chemokines
      are involved in the recruitment of specific leukocyte subsets to particular renal
      compartments. Here we summarize recent data on chemokine biology with a focus on
      the role of chemokines in the recruitment of neutrophils (polymorphonuclear
      leukocytes), monocytes/macrophages, dendritic cells, T cells, including
      regulatory T cells, and B cells in renal inflammation.

PMID- 17533006
TI  - Cytokines in glomerulonephritis.
AB  - Cytokines play central roles in both innate and adaptive immune responses that
      lead to renal inflammation. They are involved systemically in cross-talk between
      antigen-presenting cells, leukocytes, and regulatory cells to initiate and
      modulate nephritogenic immunity. Within the kidney, cytokines play a central role
      in signaling between infiltrating leukocytes and intrinsic renal cells and
      orchestrate the effector responses that lead to renal damage. Glomerulonephritis
      (GN) is an important cause of renal inflammation leading to renal failure that
      results from adaptive responses targeted at the kidney. Animal models of GN have
      shown that cytokines play critical roles in initiation and modulation of renal
      inflammatory responses through their ability to modulate the T helper 1/T helper
      2 balance of nephritogenic immune responses. Evidence from clinical studies is
      now confirming the importance of this paradigm in directing the inflammatory
      mechanisms, histologic patterns, and clinical consequences of human GN. Cytokines
      also have critical intrarenal effector roles in the development, perpetuation,
      and resolution of GN. The proinflammatory role of intrarenal cytokine production
      by leukocytes in GN is well recognized, but, more recently, the role of intrinsic
      renal cell cytokine production in amplifying renal inflammation has been shown in
      animal models of GN. Studies showing benefits of specific anticytokine therapies
      directed at tumor necrosis factor in human GN are now appearing.

PMID- 17533007
TI  - Functions of TNF and its receptors in renal disease: distinct roles in
      inflammatory tissue injury and immune regulation.
AB  - Tumor necrosis factor (TNF) alpha is a potent proinflammatory cytokine and
      important mediator of inflammatory tissue damage. In addition, it has important
      immune-regulatory functions. Many experimental studies and clinical observations
      support a role for TNF in the pathogenesis of acute and chronic renal disease.
      However, given its dual functions in inflammation and immune regulation, TNF may
      mediate both proinflammatory as well as immunosuppressive effects, particularly
      in chronic kidney diseases and systemic autoimmunity. Blockade of TNF in human
      rheumatoid arthritis or Crohn's disease led to the development of autoantibodies,
      lupus-like syndrome, and glomerulonephritis in some patients. These data raise
      concern about using TNF-blocking therapies in renal disease because the kidney
      may be especially vulnerable to the manifestation of autoimmune processes.
      Interestingly, recent experimental evidence suggests distinct roles for the 2 TNF
      receptors in mediating local inflammatory injury in the kidney and systemic
      immune-regulatory functions. In this review the biologic properties of TNF and
      its receptors, TNF receptors 1 and 2, relevant to kidney disease are summarized
      followed by a review of the available experimental and clinical data on the
      pathogenic role of the TNF system in nonimmune and immune renal diseases.
      Experimental evidence also is reviewed that supports a rationale for specifically
      blocking TNF receptor 2 versus anti-TNF therapies in some nephropathies,
      including immune complex-mediated glomerulonephritis.

PMID- 17533008
TI  - TGF-beta in renal injury and disease.
AB  - Chronic progressive kidney diseases typically are characterized by loss of
      differentiated epithelial cells and activation of mesenchymal cell populations
      leading to renal fibrosis in response to a broad range of diverse renal injuries.
      Recent evidence has indicated that epithelial microinjury leads to unbalanced
      epithelial-mesenchymal communication to initiate the fibrotic response.
      Transforming growth factors beta constitute a large family of cytokines that
      control key cellular responses in development and tissue repair. Activation of
      autocrine and paracrine transforming growth factor-beta signaling cascades in the
      context of epithelial microinjuries initiate a variety of cell type-dependent
      signaling and activity profiles, including epithelial apoptosis and epithelial-to
      mesenchymal transition, that trigger fibrogenic foci and initiate progressive
      fibrogenesis in chronic renal injury.

PMID- 17533009
TI  - The many effects of complement C3- and C5-binding proteins in renal injury.
AB  - The complement system is an important component of the innate immune system and a
      modulator of adaptive immunity. The entire complement system is focused on C3 and
      C5. Thus, there are proteins that activate C3 and C5, those that regulate this
      activation, and those that transduce the effects of C3 and C5 activation
      products; each can affect the kidney in renal injury. The normal kidney has the
      inherent capacity to protect itself from complement activation through cellular
      expression of decay-accelerating factor, membrane cofactor protein (in human
      beings), and Crry (in rodents). In addition, plasma factor H protects vascular
      spaces in the kidney. Although the main function of these proteins is to limit
      complement activation, there is now considerable evidence that they can transduce
      signals on engagement in immune cells. The G-protein-coupled 7-span transmembrane
      receptors for C3a and C5a, and the integral membrane complement receptors (CR)
      for C3b, iC3b, and C3dg, are expressed outside the kidney, particularly in cells
      of hematopoietic and immune lineage. These are important in renal injury through
      their infiltration of the kidney and/or by affecting kidney-directed immune
      responses. There is mounting evidence that intrinsic glomerular and tubular cell
      C3aR and C5aR expression and activation also can affect renal injury. CR1 on
      podocytes and the beta2 integrins CR3 and CR4 in kidney dendritic cells have
      functions that remain poorly defined. Cells of the kidney also have the capacity
      to produce and activate their own complement proteins. Thus, intrinsic renal
      cells express decay-accelerating factor, membrane cofactor protein, Crry, C3aR,
      C5aR, CR1, CR3, and CR4. These can be engaged by C3 and C5 activation products
      derived from systemic and local pools in renal injury. Given their capacity to
      provide signals that influence kidney cellular behavior, their activation can
      have substantial effects in renal injury. Defining these in a cell- and disease
      specific fashion is an exciting challenge for future research.

PMID- 17533010
TI  - Roles of lipid mediators in kidney injury.
AB  - Small lipids such as eicosanoids exert diverse and complex functions. In addition
      to their role in regulating normal kidney function, these lipids also play
      important roles in the pathogenesis of kidney diseases. Increased glomerular
      cyclooxygenase (COX)1 or COX2 expression has been reported in patients with
      nephritis and in animal models of nephritis. COX inhibitors have shown beneficial
      effects on lupus nephritis and passive Heymann nephritis, but not anti-Thy1.1
      induced nephritis. 5-Lipoxygenase-derived leukotrienes are involved in
      inflammatory glomerular injury. Lipoxygenase product 12-hydroxyeicosatetraenoic
      acid may mediate angiotensin II and transforming growth factor beta-induced
      mesangial cell abnormality in diabetic nephropathy. P450 arachidonic acid mono
      oxygenase-derived 20-hydroxyeicosatetraenoic acid and epoxyeicosatrienoic acids
      are involved in several forms of kidney injury, including renal injury in
      metabolic syndrome. Ceramide also has been shown to be an important signaling
      molecule that is involved in the pathogenesis of acute kidney injury caused by
      ischemia/reperfusion and toxic insults. Those pathways should provide fruitful
      targets for intervention in the pharmacologic treatment of renal disease.

PMID- 17533011
TI  - Matrix metalloproteinases in kidney disease progression and repair: a case of
      flipping the coin.
AB  - Matrix metalloproteinases (MMPs) have pleiotropic enzymatic actions that go far
      beyond degradation of extracellular matrix. Both the multiplicity of their
      targets and the complexity of their regulation account for a variety of
      biological effects. In renal diseases, MMP effects may be different and/or
      opposite during the different phases of the pathology evolution. The major
      challenge with future therapeutic interventions using MMP inhibitors remains how
      to accomplish temporal and spatial control of their activity without flipping the
      coin.

PMID- 17533012
TI  - Hypoxia-inducible transcription factors and their role in renal disease.
AB  - The 2 hypoxia inducible factors (HIF)-1alpha and HIF-2alpha are key mediators of
      cellular adaptation to hypoxia. They show a specific distribution pattern and
      possibly have complementary transcriptional targets in the kidney: HIF-1alpha is
      found mainly in tubular and HIF-2alpha in peritubular interstitial, endothelial,
      and glomerular cells. Both isoforms are regulated by oxygen-dependent
      hydroxylation of specific amino acid residues, which determines protein stability
      and transcriptional activity. Small molecule inhibitors of HIF hydroxylases act
      as pharmacologic inducers of HIF. HIF target genes are involved in cellular
      mechanisms that increase hypoxia tolerance or improve oxygen supply at the
      systemic or regional level, but also have been implicated in cellular apoptosis
      and profibrotic mechanisms. In experimental acute kidney injury the up-regulation
      of HIF either through endogenous hypoxia-sensing or after pharmacologic HIF
      stabilization confers tissue protection. Thus, HIF stabilization offers a
      promising novel and clinically feasible approach for nephroprotection. On the
      other hand, continuous activation of the HIF system occurs in kidney cancer and
      potentially promotes tumor growth. HIF therefore also is explored as a target for
      anticancer therapy.

PMID- 17533013
TI  - Treatment of polycystic liver disease: one size does not fit all.

PMID- 17533014
TI  - Pregnancy and CKD: any progress?

PMID- 17533015
TI  - In the literature: cancer incidence before and after kidney transplantation.

PMID- 17533016
TI  - Iron management in nondialysis-dependent CKD.
AB  - Iron deficiency has been studied extensively in patients with chronic kidney
      disease on hemodialysis therapy. However, few studies looked at iron treatment in
      the nondialysis chronic kidney disease population. Limited data suggest that iron
      deficiency is common in patients with chronic kidney disease with anemia; this
      lack of iron can hinder the effectiveness of erythropoiesis. The diagnosis of
      iron deficiency should involve clinical judgment, with an emphasis on clinical
      characteristics of the patient because of the limited amount of literature
      examining the interpretation of iron testing results. When iron deficiency is
      diagnosed in nondialysis patients with chronic kidney disease, a search must be
      initiated for any sources of blood loss. After addressing any blood loss, the
      preferred route of iron treatment must be determined. To date, no clear advantage
      was shown with intravenous versus oral administration in nondialysis patients, as
      shown in the hemodialysis setting. Thus, oral iron therapy may be a more
      reasonable option unless oral therapy previously failed. Additional research is
      needed to support evidence-based guidelines for the treatment of iron deficiency
      in the nondialysis chronic kidney disease population because this population
      differs from hemodialysis patients in the decreased extent of blood loss.

PMID- 17533017
TI  - Percutaneous transcatheter hepatic artery embolization for liver cysts in
      autosomal dominant polycystic kidney disease.
AB  - BACKGROUND: We have achieved renal contraction therapy in patients with autosomal
      dominant polycystic kidney disease (ADPKD) by means of renal transcatheter
      arterial embolization (TAE) using intravascular coils, decreasing renal size and
      improving quality of life in almost all patients. We presently perform hepatic
      TAE in patients with intractable symptomatic polycystic liver. STUDY DESIGN:
      Uncontrolled trial. SETTING & PARTICIPANTS: 30 patients with ADPKD referred for
      arteriography to an academic medical center. 22 patients had kidney failure
      treated by means of dialysis. INTERVENTION: We embolized arteries supplying
      hepatic segments replaced by cysts that were associated with well-developed
      hepatic arteries, but obstructed intrahepatic portal veins. OUTCOMES &
      MEASUREMENTS: Various volumes before and after TAE were compared by using
      computed tomography and National Institutes of Health Image software in 30
      patients with follow-up computed tomography 18 to 37 months after therapy.
      RESULTS: Total liver volume and total intrahepatic cyst volume decreased from
      7,882 +/- 2,916 and 6,677 +/- 2,978 to 6,041 +/- 2,282 and 4,625 +/- 2,299 cm(3),
      respectively (P < 0.0001 for both). Fractions of remaining (FR) total liver
      volume and FR of intrahepatic cyst volume were 78.8% +/- 17.6% and 70.4% +/-
      20.9%, respectively. Hepatic parenchyma increased from 1,205 +/- 250 to 1,406 +/-
      277 cm(3) (P = 0.0004). In 29 of 30 patients, both total liver volume and
      intrahepatic cyst volume decreased; in 1 patient, total liver volume increased
      from 5,755 to 7,069 cm(3), whereas cysts enlarged from 4,500 to 5,531 cm(3). No
      serious complications were experienced. In 24 patients, the post-TAE course was
      favorable. TAE failed to benefit 6 patients because of unrelated hepatic
      infection, peritonitis, hepatic failure, acute leukemia, or pelvic fracture.
      LIMITATIONS: Absence of a control group. CONCLUSIONS: TAE may be an option for
      patients with ADPKD with symptomatic polycystic liver who are not candidates for
      surgical treatment.

PMID- 17533018
TI  - Pregnancy in CKD stages 3 to 5: fetal and maternal outcomes.
AB  - BACKGROUND: Prognostic criteria to inform women with moderate to severe renal
      insufficiency who wish to bear children are not well established. STUDY DESIGN:
      Longitudinal multicenter cohort study. SETTINGS & PARTICIPANTS: Nondiabetic white
      women with pregnancies proceeded beyond the 20th week and estimated glomerular
      filtration rate (GFR) less than 60 mL/min/1.73 m(2) (<1 mL/s/1.73 m(2)) before
      conception. PREDICTORS: Baseline GFR and proteinuria (exposure); other clinical
      characteristics at conception (covariates). OUTCOMES & MEASUREMENTS: Difference
      in GFR decreases before conception versus after delivery (mixed linear models);
      low birth weight (<2,500 g), and maternal renal survival (logistic and Cox
      regressions). RESULTS: 49 women were studied. Mean serum creatinine and GFR at
      conception were 2.1 +/- 1 (SD) mg/dL (186 +/- 88 micromol/L) and 35 +/- 12
      mL/min/1.73 m(2) (0.58 +/- 0.2 mL/s/1.73 m(2)), respectively. Overall mean GFR
      after delivery was less than before conception (30 +/- 13.8 versus 35 +/- 12.2
      mL/min/1.73 m(2) [0.50 +/- 0.23 versus 0.58 +/- 0.20 mL/s/1.73 m(2)]; P < 0.001),
      but the rate of GFR decrease did not change (0.55 +/- 0.8 versus 0.50 +/- 0.3
      mL/min/mo [0.0092 +/- 0.013 versus 0.0083 +/- 0.005 mL/s/mo]; P = 0.661).
      Independent of potential confounders, the combined presence of baseline GFR less
      than 40 mL/min/m(2) (<0.67 mL/s/m(2)) and proteinuria with protein greater than 1
      g/d, but not either factor alone, predicted faster GFR loss after delivery
      compared with before conception (1.17 +/- 1.23 versus 0.55 +/- 0.39 mL/min/mo;
      difference, 0.62 mL/min/mo; 95% confidence interval [CI], 0.27 to 0.96 mL/min/mo
      [0.020 +/- 0.021 versus 0.0092 +/- 0.007 mL/s/mo; difference, 0.10 mL/s/mo; 95%
      CI, 0.005 to 0.016 mL/s/mo]). The presence of both risk factors, but not either
      alone, also predicted shorter time to dialysis therapy or GFR halving (N = 20;
      hazard ratio, 5.2; 95% CI, 1.7 to 15.9) and low birth weight (N = 29; odds ratio,
      5.1; 95% CI, 1.03 to 25.6). LIMITATIONS: Generalizability to other settings;
      study power. CONCLUSION: In women with renal insufficiency, the presence of both
      GFR less than 40 mL/min/1.73 m(2) (<0.67 mL/s/m(2)) and proteinuria with protein
      greater than 1 g/d before conception predicts poor maternal and fetal outcomes.

PMID- 17533019
TI  - A novel simpler histological classification for renal survival in IgA
      nephropathy: a retrospective study.
AB  - BACKGROUND: Patients with immunoglobulin A (IgA) nephropathy may progress to end
      stage renal disease (ESRD) within 10 to 20 years after renal biopsy. We evaluated
      factors associated with long-term renal survival by using a novel simplified
      histological classification. STUDY DESIGN: Retrospective study. SETTING &
      PARTICIPANTS: 437 patients (296 men, 141 women) with IgA nephropathy seen at our
      single center from January 1971 to December 2006. Most patients received
      treatment with renin-angiotensin system inhibitors. PREDICTORS: Baseline age,
      sex, presence of hematuria, presence of hypertension, serum creatinine level,
      urine protein at baseline, and 2 histological classifications. OUTCOMES &
      MEASUREMENTS: Relationship of baseline factors to time to ESRD was evaluated by
      means of univariate and multivariate analysis with log-rank test and the Cox
      proportional hazard method. RESULTS: In a mean follow-up of 107.6 months, 72 ESRD
      events occurred. The 5-, 10-, 15-, and 20-year renal survival rates after renal
      biopsy were 94.1%, 82.1%, 73.1%, and 60.3%, respectively. Independent baseline
      predictors of increased ESRD risk were microhematuria with absence of recurrent
      macrohematuria (adjusted hazard ratio [HR], 2.18; 95% confidence interval [CI],
      1.30 to 3.65; P = 0.003), 1.0 mg/dL (88.4 mumol/L) higher serum creatinine level
      (HR, 1.50; 95% CI, 1.10 to 2.07; P = 0.013), proteinuria with 1.0 g/dL (10.0 g/L)
      greater protein (HR, 1.28; 95% CI, 1.07 to 1.52; P = 0.006), and grading of
      histological lesions. A 1-grade increase according to our 3-grade classification
      was associated with a nearly 6-fold ESRD risk increase (adjusted HR, 5.95; 95%
      CI, 3.54 to 10.01; P < 0.0001). LIMITATIONS: Lack of adjustment for changes in
      treatment that may have occurred during the study period. CONCLUSIONS: Renal
      damage progression in patients with IgA nephropathy was associated with
      microscopic hematuria at clinical onset, increased serum creatinine level,
      increased proteinuria, and grading of histological lesions. Our classification
      system appears simpler than other classifications and is associated with ESRD
      risk, which could help identify individual high-risk patients and stratify
      patients enrolled in randomized clinical trials into homogeneous groups.

PMID- 17533020
TI  - A randomized trial of the effect of statin and fibrate therapy on arterial
      function in CKD.
AB  - BACKGROUND: Although patients with chronic kidney disease (CKD) are at increased
      risk of cardiovascular disease (CVD), the roles of lipid-modifying therapies in
      decreasing CVD risk are unclear. Our aim is to compare the effects of statin and
      fibrate therapy on arterial function as a risk marker of CVD. STUDY DESIGN:
      Double-blind, randomized, placebo-controlled, parallel-group study. SETTING &
      PARTICIPANTS: Ambulatory patients with stages 3 to 5 CKD. INTERVENTION: 6 weeks
      of atorvastatin, 40 mg/d, or gemfibrozil, 600 mg twice daily, with placebo.
      OUTCOMES & MEASUREMENTS: Primary outcome was arterial function assessed by means
      of endothelial-dependent flow-mediated dilatation (FMD) and small-artery
      compliance (C2). Secondary outcomes included endothelial-independent glyceryl
      trinitrate-mediated dilatation (GTNMD), large-artery compliance (C1), and levels
      of lipids, lipoproteins, and oxidized low-density lipoprotein, as well as markers
      of insulin resistance and inflammation. RESULTS: Compared with placebo,
      atorvastatin significantly decreased low-density lipoprotein (-52%), triglyceride
      (-30%), and oxidized low-density lipoprotein levels (-41%; P < 0.0001).
      Gemfibrozil significantly decreased triglyceride levels (-40%) and increased high
      density lipoprotein levels (+20%; P < 0.0001). Neither atorvastatin nor
      gemfibrozil had a significant effect on markers of insulin resistance or
      inflammation. There was no significant change in FMD, GTNMD, or C1 with either
      atorvastatin or gemfibrozil. There was improvement in C2 with atorvastatin (+1.1
      mL/mm Hg x 100) compared with placebo (P = 0.024), but not with gemfibrozil
      compared with placebo. LIMITATIONS: Small sample size leading to inadequate
      power, short duration of therapy, and use of a heterogeneous group of patients
      with CKD and dialysis patients. CONCLUSION: In patients with advanced CKD,
      atorvastatin is associated with improvement in dyslipidemia and small-artery
      stiffness, but not endothelial function. Gemfibrozil improves dyslipidemia, but
      has no effect on arterial function.

PMID- 17533021
TI  - Association between carotid artery intima-media thickness and early-stage CKD in
      a Chinese population.
AB  - BACKGROUND: Increased carotid artery intima-media thickness (IMT) predicts future
      vascular events in the general population. However, the relationship between IMT
      and chronic kidney disease (CKD) seldom was tested in subjects with early-stage
      CKD. STUDY DESIGN: Cross-sectional study. SETTING & PARTICIPANTS: 1,046 residents
      in 1 district of Beijing participated in the study. OUTCOMES & MEASUREMENTS:
      Carotid artery IMT was measured by means of high-resolution B-mode
      ultrasonography. Estimated glomerular filtration rate (eGFR) was calculated using
      the modified Modification of Diet in Renal Disease Study equation based on data
      for Chinese patients with CKD. Albuminuria was evaluated by means of urinary
      albumin-creatinine ratio on a morning spot urine sample. RESULTS: Compared with
      subjects with eGFR greater than 90 mL/min/1.73 m(2) (>1.50 mL/s/1.73 m(2)),
      subjects with eGFR of 60 to 89 mL/min/1.73 m(2) (1.00 to 1.49 mL/s/1.73 m(2)) and
      30 to 59 mL/min/1.73 m(2) (0.50 to 0.99 mL/s/1.73 m(2)) had higher mean IMT (0.74
      +/- 0.27 versus 0.82 +/- 0.30 versus 0.94 +/- 0.38 mm; P < 0.001). IMTs of
      subjects with albuminuria tended to be higher than the mean value (0.79 +/- 0.29
      versus 0.93 +/- 0.38 mm; P < 0.001). eGFR and urinary albumin-creatinine ratio
      significantly correlated with IMT in univariable analysis, but not after
      adjusting for traditional cardiovascular disease risk factors. LIMITATIONS:
      Selection bias and low prevalence of CKD might affect the strength of the study.
      CONCLUSIONS: In this Chinese population older than 40 years, carotid artery IMT
      was significantly higher in subjects with early-stage CKD. The greater prevalence
      of cardiovascular disease risk factors in patients with CKD appeared to account
      for the higher carotid artery IMT.

PMID- 17533022
TI  - Small glomeruli in WAGR (Wilms Tumor, Aniridia, Genitourinary Anomalies and
      Mental Retardation) syndrome.
AB  - BACKGROUND: Wilms tumor, aniridia, genitourinary anomalies, and mental
      retardation (WAGR) syndrome is a genetic disorder caused by a deletion of band
      11p13, which results in the loss of 1 allele of the Wilms tumor suppressor gene
      (WT1). It is not classically associated with nephropathies, but increased rates
      of renal failure are reported. Denys-Drash syndrome (DDS), caused by mutations in
      the WT1 gene affecting the third or second zinc finger, is characterized by a
      triad of glomerulopathy progressing rapidly to end-stage renal disease, male
      hermaphroditism, and Wilms tumor. In patients with DDS, small glomeruli were
      observed. METHODS: We reviewed histological findings of nontumoral kidney samples
      of 7 patients with WAGR syndrome at the time of tumor surgery. RESULTS: Median
      glomerular diameter was 110 +/- 37 microm in patients with WAGR syndrome versus
      125 +/- 18.5 microm in controls (P < 0.0001). CONCLUSION: The presence of small
      glomeruli in patients with WAGR syndrome, as in those with DDS, suggests a
      specific defect of WT1 function in development and a specific role of WT1 allele
      loss in the development of renal failure in these patients.

PMID- 17533024
TI  - Intravenous paricalcitol for treatment of secondary hyperparathyroidism in
      children on hemodialysis.
AB  - BACKGROUND: Secondary hyperparathyroidism is a common complication in children
      receiving hemodialysis. Active vitamin D is an effective therapy, but its use is
      often limited by hypercalcemia and increased calcium x phosphorus (Ca x P)
      product. Paricalcitol, a selective vitamin D receptor activator, causes less
      sustained hypercalcemia and increase in Ca x P product than calcitriol and has
      been used effectively in adult hemodialysis patients. STUDY DESIGN: Double blind,
      placebo-controlled. SETTING & PARTICIPANTS: Hemodialysis units and pediatric
      subjects receiving hemodialysis. INTERVENTION: After a washout period of 2 to 6
      weeks, 29 subjects aged 5 to 19 years received either paricalcitol or placebo for
      up to 12 weeks (0.04 mug/kg if initial intact parathyroid hormone [iPTH] level <
      500 pg/mL [ng/L]; 0.08 mug/kg if initial iPTH level > 500 pg/mL [ng/L]). The dose
      was increased by 0.04 mug/kg every 2 weeks until there was a 30% decrease in iPTH
      level from baseline or calcium level greater than 11 mg/dL (>2.74 mmol/L) or Ca x
      P product greater than 75 mg(2)/dL(2) (>6.04 mmol(2)/L(2)). OUTCOMES &
      MEASUREMENTS: Two consecutive 30% decreases from baseline in iPTH levels and
      safety of paricalcitol, including hypercalcemia and increase in Ca x P product.
      RESULTS: 60% of the paricalcitol group had 2 consecutive 30% decreases from
      baseline iPTH levels compared with 21% in the placebo group (P = 0.06). The
      paricalcitol group had a mean decrease in iPTH level of 164 pg/mL (ng/L), whereas
      the placebo group had a mean increase of 238 pg/mL (ng/L; P = 0.03). There was no
      difference from baseline to final visit in calcium, phosphorus, or Ca x P product
      values in either group. LIMITATIONS: Low power to detect differences in safety
      between groups and a short-term study. CONCLUSION: Paricalcitol decreased iPTH
      levels in children receiving hemodialysis with no significant changes in serum
      calcium, phosphorus, or Ca x P product values during the course of the study.

PMID- 17533023
TI  - Parathyroidectomy versus cinacalcet hydrochloride-based medical therapy in the
      management of hyperparathyroidism in ESRD: a cost utility analysis.
AB  - BACKGROUND: Previously, patients with end-stage renal disease (ESRD) with
      uncontrolled hyperparathyroidism had few options other than parathyroidectomy,
      which was reserved for patients refractory to medical therapy. Newer calcimimetic
      agents, such as cinacalcet, may be an alternative, but raise the possibility of
      indefinite medical treatment that also would increase costs. STUDY DESIGN: Cost
      utility analysis. SETTING & POPULATION: Base case consisted of prevalent adult US
      patients with ESRD refractory to management with standard medical therapy.
      Characteristics were obtained from patients who underwent parathyroidectomy in
      2001, and, for purposes of comparison, patients in whom cinacalcet was used were
      assigned similar characteristics. All data came from preexisting literature and
      trials or from US Renal Data System analysis files. INTERVENTION: Use of
      cinacalcet hydrochloride versus parathyroidectomy. PERSPECTIVE & TIME FRAME:
      Medicare and societal costs and quality-adjusted life-years from the date of
      parathyroidectomy or use of cinacalcet followed up for 2 years, respectively.
      MODEL & OUTCOMES: Primary outcomes were cost (measured in US dollars) and cost
      utility measured using cost per quality-adjusted life-years. RESULTS: At base
      case surgical and drug costs, surgical and drug success rates, complication
      rates/costs, and benefit from correction of hyperparathyroidism,
      parathyroidectomy was found to be both less expensive and more cost-effective at
      7.25 +/- 0.25 months. Parathyroidectomy became more cost-effective at 15.28 to
      16.32 months at the upper limit of sensitivity analysis, when drug/surgical costs
      and success/complication rates/costs were maximally weighted to favor cinacalcet
      based medical therapy. LIMITATIONS: We assumed current costs of both cinacalcet
      and parathyroidectomy and assumed cinacalcet use would be indefinite.
      CONCLUSIONS: For patients with ESRD with uncontrolled hyperparathyroidism who are
      good candidates for either drug therapy or surgery, cinacalcet hydrochloride is
      the most cost-effective modality if the patient is to remain on dialysis therapy
      for 7.25 +/- 0.25 months. Cinacalcet may be more optimal if used in patients who
      have high risk of mortality or who would expect to receive a kidney transplant
      quickly. For other subgroups, parathyroidectomy dominated.

PMID- 17533025
TI  - Radial artery-perforating vein fistula for hemodialysis.
AB  - BACKGROUND: The proximal forearm antecubital fistula described by Gracz is a
      valuable option for autogenous vascular access for hemodialysis in patients with
      destroyed forearm veins or advanced arteriosclerotic and calcified radial
      arteries. Results obtained with a variant of the Gracz fistula are presented.
      STUDY DESIGN: Patients with forearm vein destruction or failed distal
      radiocephalic fistulas were selected to have a variant of the Gracz fistula
      created and were followed up for 36 months. In each patient, the radial artery
      was anastomosed side to end or end to end to the perforating vein. Additionally,
      in some patients, the median cephalic or basilic vein was relocated
      subcutaneously to increase the accessibility of veins for puncture. SETTING &
      PARTICIPANTS: Native arteriovenous fistulas (AVFs) in the cubital region using a
      perforating vein were created in 77 patients (34 women, 43 men) referred to the
      Department of Nephrology and Transplantation Medicine, Wroclaw Medical
      University, Poland, from 1992 to 2006. OUTCOMES & MEASUREMENTS: Percentages of
      successful fistula creation and primary patency rates, defined from fistula
      placement to any maintaining intervention, and cumulative patency, defined from
      placement to fistula abandonment, were assessed. RESULTS: AVF creation was
      successful in 56 patients (73%). Primary patency rates during the follow-up
      period were 47% after 1 year, 43% after 2 years, and 39% after 3 years.
      Cumulative patency rates were 67% after 1 year, 56% after 2 years, and 53% after
      3 years. LIMITATIONS: These results reflect performance of a single center and
      thus may not be generalizable to surgeons less experienced in this technique.
      CONCLUSIONS: Radial artery-perforating vein fistulas have an acceptable survival
      rate and do not produce circulatory complications. This method may be applicable
      for AVF creation in patients with forearm vein destruction/abnormalities and as a
      rescue procedure for an old clotted fistula after kidney transplant failure.

PMID- 17533026
TI  - Early, intermediate, and long-term risk factors for mortality in incident
      dialysis patients: the Choices for Healthy Outcomes in Caring for ESRD (CHOICE)
      Study.
AB  - BACKGROUND: Knowing whether risk factors for mortality differ in dialysis
      patients who survive longer and the strengths of these risk factors for mortality
      change over time would assist physicians in making better prognostic judgments.
      STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: 1,041 incident
      dialysis patients treated in 81 clinics (mean follow-up, 3.1 years). PREDICTOR: A
      parsimonious set of risk factors (older age, white race, unemployed status,
      comorbidity, ever smoking, decreased systolic blood pressure, and decreased serum
      albumin level) chosen from several available demographic, clinical, and
      laboratory variables. OUTCOMES & MEASUREMENTS: Long-term (4+ years) survival and
      mortality over yearly intervals of follow-up, examined in logistic regression and
      Cox proportional hazards analyses. RESULTS: All baseline risk factors were
      associated with a decreased chance of surviving 4+ years, even after adjustment
      for confounders. Increased age was a strong and independent risk factor for
      mortality over all yearly intervals; comorbidity, smoking, and decreased blood
      pressure were early risk factors; low albumin level and unemployed status were
      intermediate risk factors; and white race was a late risk factor. When risk
      factors were updated with time, low albumin level and severe comorbidity became
      significant risk factors over most intervals. LIMITATIONS: Lack of some follow-up
      data and inability to rule out residual confounding or make causal inference
      based on results. CONCLUSION: Long-term survivors on dialysis therapy may have
      different risk factors for mortality than patients in earlier phases of end-stage
      renal disease (eg, race versus blood pressure); other risk factors may be
      constant over time (eg, age, comorbidity, and albumin level). Such information
      may help guide physicians in making prognostic judgments for individual patients
      with particular dialysis vintages.

PMID- 17533027
TI  - Distal renal tubular acidosis associated with anion exchanger 1 mutations in
      children in Thailand.
AB  - BACKGROUND: Mutations in the anion exchanger 1 (AE1) gene encoding the erythroid
      and kidney anion (chloride-bicarbonate) exchanger 1 may result in hereditary
      distal renal tubular acidosis (dRTA). Hemoglobinopathies are common in Thailand.
      We analyzed AE1 and hemoglobin mutations in children in Thailand with dRTA to
      evaluate their association with clinical manifestations. STUDY DESIGN: Case
      series. SETTING & PARTICIPANTS: 17 patients were recruited from 6 referral
      hospitals in 4 regions of Thailand. PREDICTORS: AE1 mutations were detected by
      means of nucleotide sequence alterations. Hemoglobin E (HbE) was detected by
      means of hemoglobin typing, and thalassemia, by means of analysis of globin
      genes. Hemolytic anemia was indicated by decreased hemoglobin and hematocrit
      values in the presence of reticulocytosis. OUTCOMES & MEASUREMENTS: Leading
      clinical manifestations in patients were failure to thrive and muscle weakness.
      Compensated or overt anemia was identified in some cases. Coexistence of AE1
      mutations with HbE or alpha(+)-thalassemia was present in a number of patients.
      RESULTS: 12 of 17 patients (70%) carried AE1 mutations, 7 patients (41%) had HbE,
      and 1 patient (6%) had alpha(+)-thalassemia. Patients with AE1 mutations
      presented with compensated hemolysis when they had metabolic acidosis. A patient
      with compound heterozygous Southeast Asian ovalocytosis/G701D and heterozygous
      alpha(+)-thalassemia showed severe hemolytic anemia. LIMITATIONS: 5 patients
      (30%) without detectable AE1 mutation also were unknown for other genetic
      abnormalities. CONCLUSIONS: Most of the patients with dRTA studied carried
      autosomal recessive AE1 mutations. Metabolic acidosis, which could be alleviated
      by adequate alkaline therapy, induced variable degrees of hemolysis in patients
      with dRTA associated with autosomal recessive AE1 mutations, especially in the
      presence of thalassemia.

PMID- 17533028
TI  - Rupture of an infected liver cyst into the pericardium in a kidney transplant
      recipient with polycystic kidney disease.
AB  - Polycystic liver disease is the most common extrarenal manifestation of autosomal
      dominant polycystic kidney disease. Hepatic cysts often are multiple, and in
      renal transplant recipients, occult infection with or without concurrent kidney
      cyst infection is a frequent cause of abdominal pain and fever and may require
      long-term antibiotic use and hospitalization. Rupture and bleeding of hepatic
      cysts into the peritoneum or viscera are infrequent complications that have been
      reported. Identification of a single culprit lesion that could be targeted for
      surgical intervention often is difficult because such imaging studies as computed
      tomographic scans, magnetic resonance images, or radionuclide-tagged white cell
      scans often show several inflamed cysts that can persist over several subsequent
      scans. Treatment may require surgical intervention. Eradication of infection and
      wound healing also is made difficult by concomitant immunosuppression in renal
      transplant recipients. We present the case of a renal transplant recipient with
      an infected dominant polycystic liver cyst that ruptured into the pericardium,
      leading to tamponade.

PMID- 17533029
TI  - Portosystemic encephalopathy in a patient treated with peritoneal dialysis.
AB  - We present a case of a 75-year-old man with end-stage renal disease caused by
      immunoglobulin A nephropathy who developed hepatic encephalopathy 15 months after
      starting continuous ambulatory peritoneal dialysis therapy. Liver test results
      were normal except for hyperammonemia (ammonia, 317 microg/dL [186 micromol/L])
      and mildly increased alkaline phosphatase and gamma-glutamyl transpeptidase
      levels. Abdominal ultrasonography showed normal liver architecture, and color
      Doppler ultrasonography showed a normal splenic-portal axis with hepatopetal
      blood flow. Histological examination of a laparoscopic liver biopsy specimen
      showed moderate fibrosis limited to portal tracts without necrosis or
      inflammation. Magnetic resonance angiography and percutaneous transhepatic portal
      angiography showed a large shunt between the left gastric and azygous veins, with
      blood flowing from the portal vein to the superior vena cava. The patient was
      transferred to hemodialysis treatment, and although his condition improved
      slightly, episodes of encephalopathy did not disappear. Surgical ligation of the
      left gastric vein was performed. In the 8 months after surgery, he has
      experienced no further episodes of hepatic encephalopathy or hyperammonemia. We
      speculate that increased intra-abdominal pressure and vasodilation caused by
      peritoneal dialysis solutions in a patient with a spontaneous portosystemic shunt
      resulted in ammonia-rich blood flow from the portal vein to the superior vena
      cava and encephalopathy. In addition, it is possible that chronic hepatic hypoxia
      caused by hypoperfusion from portosystemic shunting contributed to the
      development of liver fibrosis. To our knowledge, this is the first report of
      spontaneous portosystemic shunt encephalopathy in a patient with a noncirrhotic
      liver undergoing peritoneal dialysis.

PMID- 17533030
TI  - Cocaine, loin pain, and renal vein thrombosis.
AB  - We report an unusual renal complication of cocaine abuse in a young man who
      developed loin pain, renal vein thrombosis, and acute renal failure. Cocaine
      abuse should be considered in the differential diagnosis of renal vein thrombosis
      in young adults.

PMID- 17533031
TI  - Nephrolithiasis with hypomagnesemia: what is the cause?

PMID- 17533032
TI  - Looking at the urine: the renaissance of an unbroken tradition.
AB  - The science of looking at the urine for diagnostic purposes, uroscopy, is as
      ancient as disease. Throughout history, urine, the first bodily fluid to be
      examined, has continuously and persistently provided medicine with an increasing
      body of knowledge about the workings of the inner body. For most of its history,
      uroscopy was a visual science; this focus peaked in the Middle Ages, when the
      vessel used to examine urine, the matula, became a symbol of the medical
      profession. Over time, the practice of uroscopy spread into the hands of quacks
      and apothecaries, who prescribed and sold their potions by merely looking at the
      urine. The consequent reformation measures of the 16th and 17th centuries
      coincided with the first attempts at analyzing the contents of urine. As a
      result, many of the chemical components now reported in metabolic profiles were
      first analyzed and identified in urine during the first half of the 18th century.
      In the process, what started as a science that bordered on divination laid the
      foundations of chemical analysis and spawned the disciplines of urology,
      endocrinology, and, after the use of urine in clearance studies, nephrology. The
      analytical methods and remarkable achievements of each of these disciplines have
      increased the value of examining urine. A renaissance of this oldest diagnostic
      tool of medicine is now under way in the proteomic profiling and detection of
      biomarkers in the urine, an approach which promises to further extend the merits
      of the unbroken tradition of looking at the urine.

PMID- 17533033
TI  - C-reactive protein level in dialysis patients: weak genetic influence and
      nonspecific clinical meaning.

PMID- 17533034
TI  - Arteriovenous grafts still have a place in dialysis.

PMID- 17533039
TI  - Flow cytometry data.

PMID- 17533040
TI  - Comparative analysis of naive and memory CD4+ and CD8+ T-cell subsets in bone
      marrow and G-CSF-mobilized peripheral blood stem cell allografts: impact of donor
      characteristics.
AB  - OBJECTIVE: Donor T cells expressing lymph node homing receptors are the foremost
      initiators of acute graft-vs-host disease (aGVHD), and a high proportion of
      CD4(+)CCR7(+) T cells in human leukocyte antigen-matched allografts has been
      shown to confer a high risk of aGVHD without interfering in other outcomes.
      METHODS: Naive, central memory (T(CM)), effector memory (T(EM)), and terminally
      differentiated effector memory (T(TD)) subsets, further subdivided by CD28
      expression, were compared in 52 bone marrow and 37 granulocyte colony-stimulating
      factor-mobilized peripheral blood harvests. RESULTS: CCR7(+) cells (naive and
      T(CM)) predominated in the CD4(+) population, whereas CD8(+) memory cells were
      chiefly CCR7(neg) in the grafts. Donor age, antecedent of chronic infections, and
      graft type were independent factors influencing graft composition. CD8(+) naive
      cells negatively correlated and CD8(+) T(EM) positively correlated with age.
      Cytomegalovirus seropositivity was associated with more CD8(+) T(TD) and
      diminished CD28 expression. Toxoplasmosis seropositivity was associated with more
      CD4(+) T(CM) (p = 0.021). Marrow grafts comprised more CD28(+) cells within
      CD8(+) T(TD), but the percentage of CD4(+)CCR7(+) cells did not differ
      significantly between the two graft sources. Each of the four CD4(+) subsets and
      the percentage of CD4(+)CCR7(+) cells (p < 0.001) were correlated between graft
      and venous blood analyzed in 42 donors before harvest procedures. CONCLUSION:
      This study provides reference values for CD4(+) and CD8(+) naive and memory
      subsets within allografts applicable to the healthy donor population and
      indicates that beforehand analysis of a whole-blood sample can help evaluating
      the risk of aGVHD conferred by each donor and, when possible, choosing the one
      conferring the lowest risk.

PMID- 17533042
TI  - Iron/IRP-1-dependent regulation of mRNA expression for transferrin receptor, DMT1
      and ferritin during human erythroid differentiation.
AB  - OBJECTIVE: We investigated iron regulatory protein (IRP)-dependent expression of
      transferrin receptor (TfR), divalent metal transporter-1 (DMT1) and ferritin
      during erythroid differentiation system using an in vitro three-phase liquid
      culture. METHOD: Peripheral blood hematopoietic progenitor cells were cultured
      with interleukin-3 and stem cell factor (SCF) for 7 days (first phase),
      subsequently with SCF, erythropoietin (EPO) and insulin-like growth factor-I (IGF
      I) for 5 days (second phase), and finally with EPO and IGF-I for 3 days (third
      phase). Cells were subjected to colony assay, flow-cytometric analysis, mRNA
      assessment, electrophoretic mobility shift assay (EMSA), immunoblotting, and
      immunoprecipitation. RESULTS: In the second/third phases, erythroid cells
      serially differentiated. Expression of TfR and DMT1 mRNA, which have iron
      responsive elements (IREs) at 3'-UTR, reached a maximum on second phase, and
      thereafter decreased, while expression of ferritin mRNA, which has an IRE at the
      5'-UTR, decreased reciprocally on second phase. IRP in the cytosol after
      precipitation of polysome decreased on second phase, suggesting that IRP bound to
      IREs of these mRNAs in the polysome. When cells were incubated with (59)FeCl(3),
      (59)Fe-bound IRP-1 immunoprecipitated with anti-IRP-1 antibodies was detected on
      first phase and third phase, but was not detected on second phase. CONCLUSION:
      These results suggest that IRP-1/IRE interactions, which are supposedly induced
      after sensing a decrease of the intracellular non-Heme iron levels, play a
      crucial role on the posttranscriptional regulation of TfR, DMT1, and ferritin
      mRNAs during differentiation of normal human erythropoietic cells.

PMID- 17533041
TI  - Paradoxical drop in circulating neutrophil count following granulocyte-colony
      stimulating factor and stem cell factor administration in rhesus macaques.
AB  - OBJECTIVE: Granulocyte colony-stimulating factor (G-CSF) is frequently used
      therapeutically to treat chronic or transient neutropenia and to mobilize
      hematopoietic stem cells. Shortly following G-CSF administration, we observed a
      dramatic transient drop in circulating neutrophil number. This article
      characterizes this effect in a rhesus macaque animal model. METHODS: Hematologic
      changes were monitored following subcutaneous (SQ) administration of G-CSF. G-CSF
      was administered as a single SQ dose at 10 microg/kg or 50 microg/kg. It was also
      administered (10 microg/kg) in combination with stem cell factor (SCF; 200
      microg/kg) over 5 days. Flow cytometry was performed on serial blood samples to
      detect changes in cell surface adhesion protein expression. RESULTS: Neutrophil
      count dramatically declined 30 minutes after G-CSF administration. This decline
      was observed whether 10 microg/kg G-CSF was administered in combination with SCF
      over 5 days, or given as a single 10 microg/kg dose. At a single 50 microg/kg
      dose, the decline accelerated to 15 minutes. Neutrophil count returned to
      baseline after 120 minutes and rapidly increased thereafter. An increase in CD11a
      and CD49d expression coincided with the drop in neutrophil count. CONCLUSION: A
      transient paradoxical decline in neutrophil count was observed following
      administration of G-CSF either alone or in combination with SCF. This decline
      accelerated with the administration of a higher dose of G-CSF and was associated
      with an increase in CD11a and CD49d expression. It remains to be determined
      whether this decline in circulating neutrophils is associated with an increase in
      endothelial margination and/or entrance into extravascular compartments.

PMID- 17533043
TI  - Highly efficient gene transfer into mobilized CD34+ hematopoietic cells using
      serotype-5 adenoviral vectors and BoosterExpress Reagent.
AB  - OBJECTIVE: To optimize transduction efficiency of mobilized CD34(+) cells with
      serotype-5 adenoviruses (Ad5s), we investigated the activity of the chemical
      cocktail BoosterExpress Reagent in enhancing Ad5-mediated gene transfer into
      CD34(+) cells. METHODS: Enriched CD34(+) cells were transduced with three
      different Ad5s at increasing multiplicity of infections (MOIs) in the presence
      and absence of BoosterExpress Reagent. Percentages of transduced cells and levels
      of transgene expression were quantified by flow cytometry. Propidium iodide
      staining and colony growth were used to assess the toxicity of the transduction
      protocol. Expression of adenovirus receptors was investigated by flow cytometry.
      RESULTS: Irrespective of the Ad5 used, transduction with BoosterExpress Reagent
      using an MOI of 500 resulted in an average six- to seven-fold increase of
      transduction efficiencies and 1.5- to 2-fold increase of the levels of transgene
      expression, which could be detected up to 7 days post-transduction. Although
      BoosterExpress Reagent alone did not affect the plating efficiency of CD34(+)
      cells, adenovector transduction plus BoosterExpress Reagent significantly reduced
      the plating efficiency due to the marked increase of transduced cells. However,
      adenoviral transduction in the presence of BoosterExpress Reagent failed to
      significantly reduce the recovery of CD34(+) cells as compared with transduction
      in the absence of the compound. Coxsackievirus and adenovirus receptor as well as
      alpha(v)beta(3), alpha(v)beta(5), alpha(5), and beta(1) integrins were
      upregulated by BoosterExpress Reagent. CONCLUSIONS: BoosterExpress Reagent allows
      high-levels of durable transgene expression, thus making CD34(+) cells a suitable
      target for Ad5-mediated gene transfer.

PMID- 17533044
TI  - G-CSF treatment of canine cyclical neutropenia: a comprehensive mathematical
      model.
AB  - OBJECTIVE: To study the effects of different G-CSF temporal treatment schemes
      using a comprehensive mathematical model of the mammalian hematopoietic system
      that couples the pharmacokinetics of granulocyte colony-stimulating factor (G
      CSF) to the hematopoietic stem cell, neutrophil, platelet, and erythrocyte
      dynamics. MATERIALS AND METHODS: Data from cyclical neutropenic (CN) grey collies
      are used to build an extended model that reproduces the dynamics of circulating
      blood cells found in laboratory data from the dogs with and without daily G-CSF
      therapy. The effects of varying the treatment initiation time, and whether
      injections are given daily, every other day, or every three days, are examined.
      RESULTS: The mathematical model is able to reproduce the large variation in data
      that occurs from one dog to another. Different drug delivery times, with no other
      changes in the model parameters, can have significant long-term effects on
      neutrophil numbers. The frequency of drug delivery also has long-term effects on
      the oscillations. CONCLUSION: Using a realistic representation of the effects of
      G-CSF on the tissue-level hematopoietic system, the model matches a wide range of
      laboratory data. This implies that it would be possible to generate
      individualized predictions for specific dogs if data were available in real time.
      The proposed interventions are practical and may reduce the amount of G-CSF
      required while potentially maintaining or even improving the treatment effects.

PMID- 17533045
TI  - N-ras oncogene-induced gene expression in human hematopoietic progenitor cells:
      upregulation of p16INK4a and p21CIP1/WAF1 correlates with myeloid
      differentiation.
AB  - OBJECTIVES: Mutations in ras oncogenes occur at high frequency in acute myeloid
      leukemia and myelodysplastic syndromes; however, the role of ras genes in
      leukemogenesis has not been clearly defined. Our previous studies have shown that
      expression of mutant N-ras (N-rasG13R, G to C transversion) in human
      hematopoietic progenitor cells (HPC) promotes myeloid differentiation and
      proliferation both in vitro and in a NOD/SCID mouse model. In the present study,
      we performed expression profiling to identify the transcriptome induced by N
      rasG13R in human HPC, and analyzed the effect of mutant N-ras in sorted specific
      subpopulations of HPC. METHODS: cDNA microarray analysis was performed on cord
      blood CD34(+) cells transduced with a retrovirus containing GFP alone or in
      combination with mutant N-ras. Transduced cells were also sorted into factorial
      subpopulations according to CD34 and transgene expression, and analyzed in
      suspension or semi-solid methylcellulose culture. RESULTS: Among a variety of
      changes, including upregulation of cytokine genes, we found that N-rasG13R
      induced expression of the cyclin-dependent kinase inhibitors p16(INK4a) and
      p21(CIP1/WAF1). Analysis by RT-PCR revealed that increased p16(INK4a) and
      p21(CIP1/WAF1) occurred in the most primitive, CD34(+)/Ras(+) population but not
      in the more mature CD34(-)/Ras(+) cells or in the CD34(+)/Ras(-) cells. Moreover,
      N-rasG13R inhibited the proliferation of the primitive CD34(+)/Ras(+) cells, both
      in liquid culture and in colony assays. This growth suppression correlated with
      an increased proportion of myelomonocytic colonies and a decrease of erythroid
      colonies. In contrast, the growth of CD34(-)/Ras(+) cells and CD34(+)/Ras(-) HPC
      was not inhibited. CONCLUSIONS: These findings demonstrated the mutant N-ras
      induced transcriptome, and that this is associated with HPC growth
      suppression/myelomonocytic differentiation, and identify upregulation of cyclin
      inhibitors as key events in this process. The results indicate that ras mutation
      alone is not sufficient to induce leukemogenesis; collaborative secondary
      event(s) are involved in the process.

PMID- 17533046
TI  - CD23 is recognized as tumor-associated antigen (TAA) in B-CLL by CD8+ autologous
      T lymphocytes.
AB  - OBJECTIVE: CD23 is constitutively and atypically expressed on malignant B cells
      in patients with chronic lymphocytic leukemia (B-CLL). Here, we investigated
      whether CD23-derived peptides might function as B-CLL-specific tumor-associated
      antigen (TAA). PATIENTS AND METHODS: Using IFN-gamma-ELISPOT assays and HLA
      A2/dimer-peptide staining we identified autologous, CD23-specific HLA-A0201
      restricted T cells after 4 weeks of in vitro culture. RESULTS: We were able to
      expand autologous T cells from 8/11 B-CLL patients by using native and CD40L
      activated B-CLL cells as antigen-presenting cells (APCs) in 5 cases whereas for 3
      samples an autologous T cell response could only be evoked by use of CD40L
      stimulated B-CLL cells as APCs. The number of CD8(+) T cells could be expanded
      during 4 weeks of in vitro culture with native or CD40L-activated B-CLL cells. We
      could demonstrate that the expanded T cells were also able to secrete IFN-gamma
      upon recognition of the antigen using IFN-gamma-ELISPOT assays. Furthermore,
      these T cells not only recognized HLA-A0201-binding CD23-derived peptides
      presented by T2 cells, but also CD23-overexpressing autologous B-CLL cells in an
      MHC-I-restricted manner. CONCLUSION: In sum, CD23-derived peptides were shown to
      be naturally processed and presented as TAA in primary B-CLL, enabling the
      expansion of autologous tumor-specific T cells.

PMID- 17533048
TI  - Short telomeres in aggressive non-Hodgkin's lymphoma as a risk factor in
      lymphomagenesis.
AB  - OBJECTIVE: Telomeres cap chromosomal ends and help to maintain chromosomal
      integrity. Telomere shortening may result in chromosomal instability and,
      ultimately, malignant transformation of cells. It has not been systematically
      studied whether patients with malignancy have shortened telomeres in their
      normal, nontransformed cells, which might point to a preexisting disposition for
      chromosomal instability. METHODS: We designed an (age-) matched pair analysis
      that compared telomere length in nonmalignant peripheral leukocytes from
      previously untreated patients who recently developed an aggressive non-Hodgkin's
      lymphoma, with leukocytes from healthy individuals. RESULTS: Telomere lengths in
      B and T lymphocytes as well as granulocytes from the patients' group were
      significantly shorter than those from age-matched healthy controls. We were able
      to rule out increased proliferation, telomerase defects, or increased oxidative
      stress in patients as confounding factors of shortened telomeres. CONCLUSION:
      Short telomeres in nontransformed leukocytes may constitute a risk factor for
      lymphomagenesis.

PMID- 17533047
TI  - Imatinib effect on growth and signal transduction in polycythemia vera.
AB  - OBJECTIVE: An activating mutation of Janus kinase 2 (JAK2) in majority of
      polycythemia vera (PV) and other myeloproliferative disorders was reported. As
      imatinib inhibits several tyrosine kinases, we studied its effect in PV. PATIENTS
      AND METHODS: We employed FDCP reporter cells expressing wild-type JAK2 and mutant
      JAK2(V617F) to study the efficacy of imatinib by cell proliferation assay and its
      effect on several cell-signaling events. Imatinib's efficacy was also examined on
      in vitro expanded native human erythroid progenitors. In addition, analysis of
      the percent JAK2 T-allele and phospho-signal transducer and activator of
      transcription-5 (STAT5) in granulocytes of PV patients following imatinib therapy
      was assessed. RESULTS: Imatinib showed a specific time- and dose-dependent growth
      inhibitory effect on FDCP cells expressing JAK2(V617F), wherein we observed
      imatinib's inactivation of JAK2, STAT5 and cKIT proteins. In vitro expanded human
      PV erythroid progenitors were more sensitive to imatinib than normal erythroid
      progenitors and FDCP cells expressing JAK2(V617F), with growth inhibition at
      concentrations attainable in vivo. In an ongoing clinical study, a PV patient
      showed strong correlation between the percent JAK2 T-allele and his
      responsiveness to imatinib therapy. CONCLUSION: Our data elucidate the
      therapeutic benefit of imatinib seen in some PV patients. Our data suggest that
      JAK2/STAT5 and cKIT activation may be integrated. To our knowledge, this is the
      first report demonstrating imatinib's effect on PV erythroid progenitors. These
      studies underscore the limitation of experiments using cell lines expressing the
      gene of interest.

PMID- 17533049
TI  - Adiponectin binds to chemokines via the globular head and modulates interactions
      between chemokines and heparan sulfates.
AB  - OBJECTIVE: Adiponectin, a fat cell-derived protein, has been attracting
      considerable attention because of its antidiabetic and antiatherogenic
      activities. The aim of the present study is to identify molecules physiologically
      associating with adiponectin and to understand how the protein displays diverse
      biological activities. MATERIALS AND METHODS: We used an expression cloning
      method combined with enzyme-linked immunosorbent assay to clone adiponectin
      binding proteins from the MS-5 complementary DNA library. RESULTS: We
      successfully isolated two chemokines, stromal cell-derived factor-1 (SDF-1) and
      CCF18, and verified that adiponectin bound to them via its globular head.
      Adiponectin bound with various chemokines in vitro, such as macrophage
      inflammatory protein-1alpha (MIP-1alpha), RANTES, and monocyte chemoattractant
      protein-1 (MCP-1), suggesting that the protein had a feature commonly to bind to
      the chemokine family. The middle part of chemokines, dispensable for interacting
      with their receptors, was found to be important for the adiponectin binding.
      Although the interaction of adiponectin to SDF-1 affected neither the SDF-1-CXCR4
      binding nor the SDF-1 signaling in Jurkat cells, adiponectin and heparin mutually
      interfered in their association to SDF-1 and MCP-1 in vitro, implying that their
      association might influence the distribution of adiponectin and SDF-1 in
      inflammatory sites. Indeed, both adiponectin and SDF-1 was positively
      immunostained in vascular walls in guts from acute graft-vs-host disease
      patients. In addition, peripheral blood of adiponectin-deficient mice contained
      more hematopoietic progenitors than that of wild-type mice. CONCLUSION:
      Adiponectin may be involved in regulation of inflammation via binding to specific
      chemokines. Additionally, the interaction possibly enables adiponectin to gather
      and play its role in inflammatory sites.

PMID- 17533050
TI  - Contribution of STAT3 to the activation of survivin by GM-CSF in CD34+ cell
      lines.
AB  - OBJECTIVE: Granulocyte macrophage colony-stimulating factor (GM-CSF) has been
      shown to specifically stimulate proliferation of CD34(+) hematopoietic progenitor
      cells. Although signal transducers and activators of transcription 3 (STAT3) is
      believed essential for transduction of GM-CSF-induced cell proliferation, the
      signaling mediated by STAT3 is not completely understood. Because survivin
      regulates cell proliferation and survival via its antiapoptotic function, we
      studied the link between STAT3 signaling and survivin expression in CD34(+)
      cells. METHODS: GM-CSF-induced STAT3 and survivin expression in CD34(+) cells was
      examined by Western blot assay. GM-CSF-activated survivin promoter activity was
      analyzed by gene transfection and reporter assays. The binding of STAT3 to the
      survivin promoter was evaluated by chromatin immunoprecipitation and
      electrophoretic mobility shift assay. Western blotting and flow cytometry were
      utilized to test the effect of Janus family of tyrosine kinases (JAK) inhibitor
      and STAT3 small interfering RNA (siRNA) on cell apoptosis. RESULTS: We found that
      GM-CSF stimulates survivin promoter activity in CD34(+) KG-1 cells, and STAT3
      binds to the core survivin promoter containing a STAT response element TT(N)(5)AA
      at sites -264 to -256. Mutation or deletion of this STAT response element
      completely abolished the effects of GM-CSF on survivin promoter activity.
      Furthermore, addition of either JAK inhibitor or STAT3 siRNA was able to inhibit
      GM-CSF-induced survivin promoter activity and survivin expression. Inhibition of
      survivin by STAT3 siRNA or by withdrawal of GM-CSF in a GM-CSF-dependent, CD34(+)
      line TF-1 decreased cell growth and increased apoptosis. CONCLUSION: Altogether,
      our results suggest that survivin is a transcriptional target of STAT3, and that
      GM-CSF-stimulated CD34(+) cell proliferation is regulated by the
      JAK/STAT3/survivin signaling pathway.

PMID- 17533051
TI  - CD34 human hematopoietic progenitor cell line, MUTZ-3, differentiates into
      functional osteoclasts.
AB  - OBJECTIVE: CD14(+) monocyte cell lines can differentiate into an osteoclast (OC)
      like lineage. However, the identification of human cell lines with stem cell
      characteristics, capable of differentiating into OCs, would provide a tool for
      the study of the molecular mechanisms regulating their commitment,
      differentiation, and function. Since the human acute myeloid leukemia cell line
      MUTZ-3 contains both CD34(+) stem cell and CD14(+) cell populations, we
      investigated the capacity of the stem/progenitor CD34(+) population to
      differentiate into functional OCs. MATERIALS AND METHODS: Sorted MUTZ-3-CD34(+)
      and MUTZ-3-CD14(+) cells were cultured in presence of M-CSF, RANK-L, and TNF
      alpha to generate OCs. Differentiation was evaluated by TRAP staining and RT-PCR,
      which assessed the expression of c-fms, RANK, MMP-9, CATK, TRAP, and CTR in 
      CD34(+)OC and -CD14(+)OC cells. Resorption pit formation was also evaluated.
      CD34, CD14, M-CSF-R, RANK, and CTR expression was assessed by FACS analysis.
      RESULTS: MUTZ-3-CD34(+) differentiated into OCs, displaying the full range of
      differentiation markers; MMP-9, CATK, TRAP, and RANK mRNA were detected from day
      3 of culture, whereas CTR from day 12. Stimulated MUTZ-3-CD34(+) generated
      functional osteoclasts that formed extensive resorption lacunae on both
      mineralized surface and bone slices. Surprisingly, in both sorted populations we
      identified a population M-CSF-R(+)/RANK(+) that at the same time co-expressed
      CD14 and CD34. CONCLUSIONS: These findings demonstrate that MUTZ-3 cells
      constitute an invaluable model to study the expression pattern in different
      developmental stages of commitment and differentiation. Importantly, the data
      indicate that the CD14(+)CD34(+)M-CSF-R(+)RANK(+) population represents an
      intermediate stage of differentiation from CD34 precursors and monocytes to
      osteoclast.

PMID- 17533052
TI  - Expression of AML/Runx and ETO/MTG family members during hematopoietic
      differentiation of embryonic stem cells.
AB  - Runx1/AML1 plays important roles in hematopoiesis, including the commitment of
      cells to hematopoiesis during embryonic development, and in the maintenance of
      hematopoietic cell populations. It is also one of the most common genes involved
      in chromosomal translocations related to leukemia. One such translocation is
      t(8;21), which fuses the Runx1 gene to the MTG8/ETO gene and generates the Runx1
      MTG8 (AML1-ETO) fusion gene. Both Runx1 and MTG8 have two additional family
      members that are much less studied in hematopoiesis. Here we report the
      expression of every member of the Runx and MTG families as well as the Runx
      heterodimerization partner CBFbeta during hematopoietic differentiation of murine
      embryonic stem cells. We observed substantially increased expression of Runx1,
      Runx2, and MTG16 during hematopoietic differentiation. Furthermore, the increase
      in Runx2 expression is delayed relative to Runx1 expression, suggesting their
      possible sequential contribution to hematopoiesis.

PMID- 17533054
TI  - Field Emission 2006. Proceedings of the 50th International Field Emission
      Symposium and the 19th International Vacuum Nanoelectronics Conference. July 17
      20, 2006. Guilin, China.

PMID- 17533053
TI  - Fucoidan ingestion increases the expression of CXCR4 on human CD34+ cells.
AB  - OBJECTIVE: Transplantation of hematopoietic progenitor stem cells (HPC) is an
      important treatment modality for a variety of neoplastic diseases. HPC collection
      for transplantation with granulocyte colony-stimulating factor may be
      unsuccessful in patients who have received prior chemotherapy or for other
      reasons. Methods to improve mobilization of HPCs are required. Disruption of the
      interaction between the cell surface receptor CXCR4 and its ligand stromal
      derived factor-1 (SDF-1) is a mechanism for HPC release from the bone marrow into
      the peripheral blood (PB). METHODS: We carried out a clinical trial to evaluate
      the effects of ingestion of a fucoidan, galactofucan sulfate (a putative HPC
      mobilizing agent) on circulating CD34(+) cells, CXCR4 expression, and levels of
      SDF-1, interferon gamma (IFN-gamma) and interleukin 12. RESULTS: Following
      ingestion of fucoidan, CD34(+) cells increased significantly in the PB from 1.64
      to 1.84 cells/microL after 4 days. The proportion of CD34(+) cells that expressed
      CXCR4 increased from 45 to 90% after 12 days, the plasma level of SDF-1 increased
      from 1978 to 2010 pg/mL, and IFN-gamma level increased from 9.04 to 9.89 pg/mL.
      CONCLUSION: Oral fucoidan significantly amplified the CXCR4(+) HPC population.
      The ability to mobilize HPC using sulfated polysaccharides and mobilize more HPC
      with high levels of CXCR4 could be clinically valuable.

PMID- 17533060
TI  - Assessing state immunization requirements for healthcare workers and patients.
AB  - BACKGROUND: Laws requiring vaccination for school entry have resulted in high
      coverage and reduced disease incidence; however, few data exist on the use of
      similar laws in other settings. This study reviews laws regulating vaccination of
      healthcare workers (HCWs) and patients in selected healthcare delivery settings.
      METHODS: From September 2004 to June 2005, Lexis-Nexis and other web-based
      databases were searched for laws pertaining to HCW and patient vaccination in 50
      states and Washington DC. Laws were grouped by population, setting, vaccine type,
      and voluntary versus mandatory vaccination. Data were analyzed in 2006. RESULTS:
      Over half of states (n=32) have laws for HCW vaccination in traditional
      healthcare settings (hospitals, ambulatory care), while only seven states have
      laws for patients in these settings. Most laws regulating vaccine administration
      for HCWs were voluntary; requirements for mandatory immunization were most common
      for institutionalized populations. CONCLUSIONS: Significant state-to-state
      variation exists in laws for vaccination of HCWs and patients. Additional data
      are needed on how such vaccination requirements affect coverage in these
      populations. Model legislation may be helpful to states wishing to implement
      immunization requirements.

PMID- 17533061
TI  - Exposure to smoking in popular contemporary movies and youth smoking in Germany.
AB  - BACKGROUND: Studies have linked exposure to movie smoking and smoking initiation
      among adolescents in the United States, but there has been only one published
      study of adolescents outside the U.S. METHOD: A cross-sectional survey of 5586
      schoolchildren aged 10-17 with a mean of 12.8 (SD=1.2) years from randomly
      selected secondary schools in Schleswig-Holstein, Germany, was taken in
      October/November 2005. In August 2006, using previously validated methods,
      exposure to movie smoking was estimated from 398 internationally distributed
      films (98% produced and distributed by U.S. studios) released in Germany and
      examined its relationship with ever and current (30-day) smoking. RESULTS:
      Overall, 40.7% of the sample had tried smoking, and 12.3% were current smokers.
      The sample quartile (Q) of movie smoking exposure was significantly associated
      with the prevalence of smoking initiation: 0.17 of adolescents in Q1 had tried
      smoking; 0.35 in Q2; 0.47 in Q3; and 0.64 in Q4. Movie smoking exposure was
      significantly associated with the prevalence of current smoking: 0.03 for
      adolescents in Q1; 0.08 in Q2; 0.14 in Q3; and 0.25 in Q4. After controlling for
      sociodemographics, parent/friend/sibling smoking, school performance, personality
      characteristics, TV consumption, receptivity to tobacco marketing, and parenting
      style, the adjusted odds ratios for having tried smoking were 1.7 (95% confidence
      interval [CI]=1.4-2.1) for Q2, 1.8 (95% CI=1.5-2.3) for Q3, and 2.2 (95% CI=1.8
      2.8) for Q4 compared with adolescents in Q1. The adjusted odds ratios for current
      smoking were 1.4 (95% CI=0.9-2.2) for Q2, 1.7 (95% CI=1.1-2.6) for Q3, and 2.0
      (95% CI=1.3-3.1) for Q4 compared with adolescents in Q1. CONCLUSIONS: Smoking in
      internationally distributed movies is associated with ever and current smoking
      among German adolescents. This suggests the need for prospective studies of this
      association in countries other than the U.S. and research into the potential
      impact of countrywide policies that would limit exposure of young adolescents to
      movie smoking.

PMID- 17533062
TI  - Medical costs and productivity losses due to interpersonal and self-directed
      violence in the United States.
AB  - BACKGROUND: Violence-related injuries, including suicide, adversely affect the
      health and welfare of all Americans through premature death, disability, medical
      costs, and lost productivity. Estimating the magnitude of the economic burden of
      violence is critical for understanding the potential amount of resources that can
      be saved if cost-effective violence prevention efforts can be broadly applied.
      From 2003 to 2005, the lifetime medical costs and productivity losses associated
      with medically treated injuries due to interpersonal and self-directed violence
      occurring in the United States in 2000 were assessed. METHODS: Several nationally
      representative data sets were combined to estimate the incidence of fatal and
      nonfatal injuries due to violence. Unit medical and productivity costs were
      computed and then multiplied by corresponding incidence estimates to yield total
      lifetime costs of violence-related injuries occurring in 2000. RESULTS: The total
      costs associated with nonfatal injuries and deaths due to violence in 2000 were
      more than $64.8 [corrected] billion. Most of this cost ($64.4 billion or 92%) was
      due to lost productivity. However, an estimated $5.6 billion was spent on medical
      care for the more than 2.5 million injuries due to interpersonal and self
      directed violence. CONCLUSIONS: The burden estimates reported here provide
      evidence of the large health and economic burden of violence-related injuries in
      the U.S. But the true burden is likely far greater and the need for more research
      on violence surveillance and prevention are discussed.

PMID- 17533063
TI  - Discontinuing hormone replacement therapy: attenuating the effect on CVD risk
      with lifestyle changes.
AB  - BACKGROUND: Concern about the potential risks associated with hormone replacement
      therapy (HRT) has left post-menopausal women and healthcare providers searching
      for safe and effective means for cardiovascular disease (CVD) risk factor
      reduction. METHODS: The Woman On the Move through Activity and Nutrition study is
      a 5-year clinical trial (2002-2006) designed to test whether a lifestyle
      intervention will reduce measures of subclinical CVD. Participants were
      randomized at baseline to a health education or lifestyle change group. The
      impact of lifestyle intervention on CVD risk factors was examined in 240 women
      who were initially on HRT at baseline and either continued (n = 110) or
      discontinued (n = 130) by 18 months. RESULTS: The lifestyle-change group
      significantly decreased weight, body mass index, waist circumference (all
      p<0.0001), total cholesterol (p=0.02), and LDL cholesterol (LDL-C) (p= 0.01),
      improved fat intake (p<0.0001), and increased leisure physical activity (p=0.005)
      when compared with the health education group. HRT discontinuation resulted in
      increased total cholesterol (p=0.04) and LDL-C (p=0.009). CVD risk factor changes
      were further explored by the HRT group, stratified by randomized group
      assignment. Within the health education arm, HRT discontinuers averaged over a 22
      mg/dL increase in total cholesterol and LDL-C, while HRT continuers averaged less
      than 4 mg/dL (p=0.004 and 0.002, respectively). No such differences were noted in
      the lifestyle-change group (p=0.78 and 0.90, respectively). CONCLUSIONS:
      Lifestyle modification was effective for CVD risk factor reduction in post
      menopausal women. HRT discontinuation resulted in increased total cholesterol and
      LDL-C, which were successfully attenuated by a lifestyle intervention
      incorporating weight loss, physical activity, and dietary modification.

PMID- 17533064
TI  - Long-term physical activity patterns and health-related quality of life in U.S.
      women.
AB  - BACKGROUND: Despite studies showing that physically active individuals report
      higher quality-of-life scores, few data exist on the impact of changing physical
      activity levels on subsequent changes in quality of life. METHODS: Subjects were
      63,152 women in the Nurses' Health Study aged 40 to 67 years in 1986. Women
      reported their physical activity on questionnaires in 1986, 1988, 1992, 1994, and
      1996, and were grouped according to quartile of change in activity from 1986 to
      1996. Women also reported seven health-related quality-of-life dimensions in 1996
      and 2000 using the Medical Outcomes Study Short-Form 36 Health Status Survey. The
      main outcome measures were scores for each of these seven dimensions in 1996, as
      well as changes in each of these dimensions from 1996 to 2000. Data were analyzed
      in 2006. RESULTS: In age and baseline activity adjusted analyses, compared to
      women whose physical activity was relatively stable from 1986 to 1996, women who
      saw any increase in physical activity levels had higher quality-of-life scores in
      1996. Among women with a clear increase in physical activity, the increase in
      quality-of-life scores ranged from 2.23 (95% confidence intervals [CI]=1.94-2.52)
      for mental health to 8.23 (95% CI=7.49-8.97) for role limitations due to physical
      problems. Increasing physical activity also was associated with greater increases
      in quality-of-life scores from 1996 to 2000 compared to women whose physical
      activity level was stable. The strongest association was for role limitations due
      to physical problems, where women with a clear increase in physical activity had
      a significant improvement (1.81, 95% CI=1.09-2.53) in the outcome. CONCLUSIONS:
      Long-term physical activity patterns are an important determinant of health
      related quality of life.

PMID- 17533065
TI  - Fitness facilities for adults: differences in perceived access and usage.
AB  - BACKGROUND: Perceived access to places for physical activity may play an
      important role in influencing physical activity behavior. Little is known about
      the prevalence of perceived access to facilities for physical activity. METHODS:
      Cross-sectional analysis of a national sample of 27,894 adults from the 2002
      National Health Interview Survey was performed to describe the characteristics of
      those who perceived that they have access to fitness facilities, and determine
      the prevalence of perceived access, reported use of fitness facilities, and
      reported barriers to the use of fitness facilities. Analyses were conducted in
      2005 and 2006. RESULTS: Approximately 61% of adults reported having access to
      fitness facilities. Perceived access was highest among adults aged 34 and
      younger, non-Hispanic whites, those with a college education, among adults with a
      body mass index of less than 35 kg/m(2), and among those with higher physical
      activity levels. The most commonly reported perceived barrier to access was cost.
      Almost 21% of U.S. adults (37.0% of active, 19.9% of intermittently active, 6.0%
      of inactive) reported having used a health club, wellness program, or fitness
      facility at least ten times during the past year. CONCLUSIONS: Fitness facilities
      provide one option for increasing access to places to be physically active.
      Having access to fitness facilities is significantly associated with physical
      activity levels among U.S. adults.

PMID- 17533066
TI  - Equitable access to exercise facilities.
AB  - BACKGROUND: Leisure-time physical activity patterns are low and socially
      patterned. Ecologic studies of the provision of exercise facilities indicate that
      in areas of deprivation, there is a trend toward reduced availability of exercise
      facilities compared with more affluent areas. Existing studies are restricted to
      single geographic areas or regions. In this study, national-level data were used
      to examine the relationship between neighborhood deprivation and the density of
      physical activity facilities in England. METHODS: A database of all indoor
      exercise facilities in England was obtained, and facilities were linked to
      administrative areas and assigned a deprivation score. Census data were used to
      calculate the density of physical activity facilities per 1000 people per
      quintile of deprivation. The exercise facilities data were collected in 2005, and
      the analysis was conducted in 2006. RESULTS: When all 5552 facilities were
      considered, there was a statistically significant negative relationship (p<0.001)
      between area deprivation score and the density of physical activity facilities. A
      similar relationship was observed when public and private facilities were
      examined separately. When only swimming pools were examined, a negative
      association was observed for public pools (p<0.0001) but not those that were
      private (p=0.50), which were more evenly distributed among quintiles of area
      deprivation. CONCLUSIONS: The availability of physical activity facilities
      declines with level of deprivation. Areas in most need of facilities to assist
      people live physically active lifestyles have fewer resources.

PMID- 17533067
TI  - Active transportation to school: trends among U.S. schoolchildren, 1969-2001.
AB  - BACKGROUND: Rising rates of overweight children have focused attention on walking
      and biking to school as a means to increase children's physical activity levels.
      Despite this attention, there has been little documentation of trends in school
      travel over the past 30 years or analysis of what has caused the changes in mode
      choice for school trips. METHODS: This article analyzes data from the 1969, 1977,
      1983, 1990, 1995, and 2001 National Personal Transportation Survey conducted by
      the U.S. Department of Transportation to document the proportion of students
      actively commuting to school in aggregate and by subgroups and analyze the
      relative influence of trip, child, and household characteristics across survey
      years. All analyses were done in 2006. RESULTS: The National Personal
      Transportation Survey data show that in 1969, 40.7% (95% confidence interval
      [CI]=37.9-43.5) of students walked or biked to school; by 2001, the proportion
      was 12.9% (95% CI=11.8-13.9). Distance to school has increased over time and may
      account for half of the decline in active transportation to school. It also has
      the strongest influence on the decision to walk or bike across survey years.
      CONCLUSIONS: Declining rates of active transportation among school travelers
      represents a worrisome loss of physical activity. Policymakers should continue to
      support programs designed to encourage children to walk to school such as Safe
      Routes to School and the Centers for Disease Control and Prevention's KidsWalk.
      In addition, officials need to design policies that encourage schools to be
      placed within neighborhoods to ensure that the distance to school is not beyond
      an acceptable walking distance.

PMID- 17533068
TI  - Melanoma early detection with thorough skin self-examination: the "Check It Out"
      randomized trial.
AB  - BACKGROUND: Monthly thorough skin self-examination (TSSE) is an important
      practice for early melanoma detection that is performed by a small minority of
      the population. DESIGN: A randomized trial was conducted to determine whether a
      multicomponent intervention can increase TSSE performance and to describe the
      effects on performance of skin surgeries compared with a similar control
      intervention focused on diet. SETTING/PARTICIPANTS: One thousand three hundred
      fifty-six patients attending a routine primary care visit in southeastern New
      England participated in this trial. INTERVENTIONS: Participants received
      instructional materials, including cues and aids, a video, and a brief counseling
      session and (at 3 weeks) a brief follow-up phone call (from a health educator)
      and tailored feedback letters. MEASURES: Performance of TSSE assessed by
      telephone interview and having a surgical procedure performed on the skin were
      confirmed by examining medical records. RESULTS: TSSE was performed by
      substantially more participants at 2, 6, and 12 months in the intervention group
      than in the control group (55% vs 35%, p<0.0001 at 12 months). We also noted that
      a substantially higher proportion in the intervention group had skin surgery in
      the first 6 months (8.0% vs 3.6%, p=0.0005), but there was no difference at 6 to
      12 months (3.9% vs 3.3%, p=0.5). CONCLUSIONS: The TSSE intervention was effective
      in increasing performance of TSSE, in that it resulted in increased surgery on
      the skin, and that increase in skin procedures only persisted for 6 months.
      Intervention to increase TSSE may result in long-term benefit in early detection
      of melanoma while causing only a short-term excess of skin surgeries.

PMID- 17533070
TI  - Youth Internet users at risk for the most serious online sexual solicitations.
AB  - BACKGROUND: This article explores changes in the prevalence of youth Internet
      users reporting unwanted sexual solicitations between 2000 and 2005, as well as
      the risk factors related to reports of the most serious solicitations, aggressive
      solicitations, in which solicitors attempted or made offline contact with youth.
      METHODS: Data were collected from two cross-sectional random-digit-dial telephone
      surveys of Internet-using youth (aged 10 to 17) in the United States. RESULTS:
      Although sexual solicitations declined overall since 2000, in 2005 youth were 1.7
      times more likely to report aggressive solicitations, even when adjusting for
      changes in demographic and Internet-use characteristics. Risk factors for
      aggressive solicitations included being female, using chat rooms, using the
      Internet with a cell phone, talking with people met online, sending personal
      information to people met online, talking about sex online, and experiencing
      offline physical or sexual abuse. CONCLUSIONS: Further research is warranted into
      the implications of aggressive online sexual solicitation and how to address and
      prevent such experiences.

PMID- 17533069
TI  - Cancer screening in women: body mass index and adherence to physician
      recommendations.
AB  - BACKGROUND: The reasons that obese women are less likely to obtain mammograms and
      Papanicolaou tests (Pap smears) are poorly understood. This study evaluated
      associations between body mass index (BMI) and receipt of and adherence to
      physician recommendations for mammography and Pap smear. METHODS: Data from the
      2000 National Health Interview Survey (8289 women aged 40 to 74 years) were
      analyzed in 2006 using logistic regression. Women with previous hysterectomy were
      excluded from Pap smear analyses (n=5521). Outcome measures were being up-to-date
      with screening, receipt of physician recommendations, and women's adherence to
      physician recommendations for mammography and Pap smear. RESULTS: After adjusting
      for sociodemographic variables, healthcare access, health behaviors, and
      comorbidity, severely obese women (BMI > 40 kg/m(2)) were less likely to have had
      mammography within 2 years (odds ratio [OR]=0.50, 95% confidence interval
      [CI]=0.37-0.68) and a Pap smear within 3 years (OR=0.43, 95% CI=0.27-0.70). Obese
      women were as likely as normal-weight women to receive physician recommendations
      for mammography and Pap smear. Severely obese women were less likely to adhere to
      physician recommendations for mammography (OR=0.49, 95% CI=0.32-0.76). Women in
      all obese categories (BMI > 30 kg/m(2)) were less likely to adhere to physician
      recommendations for Pap smear (ORs ranged from 0.17 to 0.28, p<0.001).
      CONCLUSIONS: Obese women are less likely to adhere to physician recommendations
      for breast and cervical cancer screening. Interventions focusing solely on
      increasing physician recommendations for mammography and Pap smears will probably
      be insufficient for obese women. Additional strategies are needed to make cancer
      screening more acceptable for this high-risk group.

PMID- 17533071
TI  - Predictors of smallpox vaccination among healthcare workers and other first
      responders.
AB  - BACKGROUND: The goal of the National Smallpox Vaccination Program was to
      vaccinate a cadre of healthcare workers and first responders who could care for
      smallpox patients in the event of an attack. METHODS: Using a convenience sample
      of 36 health departments and 34 hospitals in California, we conducted a telephone
      interview between July 2003 and April 2004 of healthcare workers and first
      responders to determine predictors of smallpox vaccination. FINDINGS: The
      response rate was 54.1%. Of 477 respondents with no contraindications to
      vaccination, 106 were vaccinated and 371 were unvaccinated. Among the vaccinated,
      the leading reason for vaccination was wanting to be part of a smallpox response
      team (74%). Among the unvaccinated, leading reasons for not being vaccinated
      included thinking the risk of smallpox was not high enough (25%) and concern
      about side effects (19%). Factors independently associated with vaccination
      include previous smallpox vaccination (adjusted odds ratio [AOR]=4.1, 95%
      confidence interval [CI]=1.2-14.1), having little or no concern about vaccine
      adverse events (AOR=3.0, CI=1.3-7.0, compared with somewhat/very), reporting
      their employer had a policy to reimburse for travel or other out of pocket costs
      (AOR=2.5, CI=1.1-5.7, compared with no policy), very high to high chance of
      compensation if adverse events occurred (AOR=2.9, CI=1.2-6.3, compared with low
      chance), and answering in the negative to questions about concerns about
      potential costs. Blacks were less likely than whites to be vaccinated (AOR=0.04,
      CI=0.03-0.6). CONCLUSIONS: Clearly communicating the risks and benefits of
      vaccination and addressing issues of cost, convenience, and compensation may be
      important for any program where vaccination is provided in the national interest
      and when the direct benefits of vaccination are unknown.

PMID- 17533072
TI  - The 2006 Report of the Surgeon General: the health consequences of involuntary
      exposure to tobacco smoke.

PMID- 17533073
TI  - Protecting patients from harm: legislating vaccinations for healthcare workers.

PMID- 17533076
TI  - Alcohol-associated pancreatitis.
AB  - Only a small proportion of heavy drinking individuals develop pancreatitis. The
      environmental and host cofactors shown to have an association with alcoholic
      pancreatitis are smoking and race. The known genetic variations and polymorphisms
      do not seem to play an important role in alcoholic pancreatitis. Newer
      developments in the understanding of complex disorders allow clinicians to
      understand better the role of cofactors and interactions between known and yet
      unknown environmental and genetic factors in causing alcoholic pancreatitis.

PMID- 17533077
TI  - Autoimmune pancreatitis.
AB  - Autoimmune pancreatitis (AIP) is a benign, IgG4-related, fibroinflammatory form
      of chronic pancreatitis that can mimic pancreatic ductal adenocarcinoma both
      clinically and radiographically. Laboratory studies typically demonstrate
      elevated serum IgG4 levels and imaging studies reveal a diffusely or focally
      enlarged pancreas with associated diffuse or focal narrowing of the pancreatic
      duct. The pathologic features include periductal lymphoplasmacytic inflammation,
      obliterative phlebitis, and abundant IgG4-positive plasma cells. The treatment of
      choice for AIP is steroid therapy. Diagnostic criteria for AIP have been proposed
      that incorporate histologic, radiographic, serologic, and clinical information.

PMID- 17533078
TI  - Incidence, risk factors, and prevention of post-ERCP pancreatitis.
AB  - Pancreatitis is the most common complication of endoscopic retrograde
      cholangiopancreatography (ERCP). Because of the potential risks and consequences
      of post-ERCP pancreatitis, considerable efforts have been made to define patient-
      and procedure-related factors that may be associated with an increased risk of
      this complication, along with determining interventions that can be done to
      reduce post-ERCP pancreatitis.

PMID- 17533079
TI  - Risk and markers of severe acute pancreatitis.
AB  - Acute pancreatitis begins with pancreatic injury, elicits an acute inflammatory
      response, and encompasses a variety of potential complications in a subset of
      patients. Early determination of severity and risk of complications is crucial
      for instituting immediate interventions to improve outcome. The severity of acute
      pancreatitis is a function of the amount of pancreas that is injured and the
      intensity of the inflammatory response. Early death is mainly linked to an
      overwhelming inflammatory response leading to cardiovascular collapse or acute
      respiratory distress syndrome, whereas late death is associated with infected
      pancreatic necrosis and sepsis. This article reviews recent advancements in
      understanding the pathogenesis, immunology, and genetics of severe acute
      pancreatitis, and the literature on laboratory-based markers, which predict a
      severe clinical course and pancreatic necrosis.

PMID- 17533080
TI  - Nutrition support in severe acute pancreatitis.
AB  - Nutritional support can improve the outcome from severe acute pancreatitis in two
      ways: first by providing the building blocks for tissue repair and recovery, and
      second, by modulating the inflammatory response and preventing organ failure,
      both of which are responsible for most of the morbidity and mortality associated
      with the disease. This review discusses the evidence on which these statements
      are based.

PMID- 17533081
TI  - Necrotizing pancreatitis.
AB  - Necrotizing pancreatitis continues to challenge clinicians, and few other medical
      subjects currently elicit as much debate. Host characteristics or underlying
      differences in pathophysiology that lead to pancreatic necrosis remain poorly
      understood. Severe pancreatitis follows a two-phase clinical course. The early
      first phase manifests the features of the systemic inflammatory response
      syndrome, and the second late phase is characterized by infectious complications.
      This article presents a multidisciplinary literature-based approach to the
      treatment of patients with necrotizing pancreatitis.

PMID- 17533082
TI  - Genetic counseling for nonsyndromic pancreatitis.
AB  - An appreciation for the background of disease, not to mention the medical
      management of individuals, may be significantly affected by testing for mutations
      and genetic variants associated with pancreatitis. Pretest and posttest
      counseling are essential for patients and families to benefit fully from genetic
      testing for a susceptibility to develop pancreatitis. The clinician, often
      working directly with a qualified genetic counselor, must ensure that patients
      and families appreciate the benefits and limitations of genetic tests, that
      results are interpreted accurately, and that patients understand implications of
      information for both their medical care and personal decisions. This article
      focuses on the approach to genetic counseling for pancreatitis and implications
      of recent advances.

PMID- 17533083
TI  - Pain in chronic pancreatitis and pancreatic cancer.
AB  - Chronic, debilitating abdominal pain is arguably the most important component of
      chronic pancreatitis, leading to significant morbidity and disability. Attempting
      to treat this pain, which is too often unsuccessful, is a frustrating experience
      for physician and patient. Multiple studies to improve understanding of the
      pathophysiology that causes pain in some patients but not in others have been
      performed since the most recent reviews on this topic. In addition, new treatment
      modalities have been developed and evaluated in this population. This review
      discusses new advances in neuroscience and the study of visceral pain mechanisms,
      as well as genetic factors that may play a role. Updates of established
      therapies, as well as new techniques used in addressing pain from chronic
      pancreatitis, are reviewed. Lastly, outcome measures, which have been highly
      variable in this field over the years, are addressed.

PMID- 17533084
TI  - Cystic neoplasms of the pancreas.
AB  - This article presents the approach to the most commonly encountered pancreatic
      cystic masses that the authors employ at the University of Pittsburgh Medical
      Center. Variations on this approach are to be expected, based on several factors,
      including the availability of sophisticated imaging equipment and personnel.

PMID- 17533085
TI  - Intraductal papillary mucinous neoplasia.
AB  - Intraductal papillary mucinous neoplasia is a neoplastic disorder of varying
      degree and extent that affects the pancreatic ductal epithelium. Clinical
      presentations may vary from an asymptomatic incidental finding to obstructive
      jaundice. Harbingers of malignancy include symptoms of jaundice, weight loss, or
      new-onset diabetes. In the absence of findings that correlate with malignancy,
      natural history is unknown. Management of these patients is controversial, and
      should be individualized based on surgical risk.

PMID- 17533086
TI  - Multimodality therapy for pancreatic cancer.
AB  - Neoadjuvant chemoradiotherapy can be administered safely to patients with
      pancreatic cancer. Complete pathologic responses are rare, however, and the
      benefits of this approach compared with standard adjuvant therapy are uncertain.
      The only way to evaluate the efficacy of neoadjuvant chemoradiotherapy is a
      prospective trial involving a uniform patient population comparing the results of
      neoadjuvant and adjuvant therapy and a cohort receiving surgery alone. Such a
      study can be designed in an ethically sound manner but requires the collaboration
      of numerous institutions and careful coordination to achieve statistically
      conclusive results. The future of pancreatic cancer research rests on the
      availability and rapid transfer of new therapies from the laboratory to clinical
      research.

PMID- 17533087
TI  - Early detection and staging of adenocarcinoma of the pancreas.
AB  - Early diagnosis is likely to improve the outcome and survival in patients who
      have pancreatic cancer. The sensitivity and specificity of current screening
      methods, however, limit their applicability to individuals at high risk for
      developing pancreatic cancer. Further development of serum markers may lead to
      improved diagnostic accuracy and allow screening to be implemented more broadly.
      Proteomic profiling and evaluation of panels of markers hold particular promise
      for the future. This article provides a review of current methods and results for
      the early detection and staging of pancreatic cancer, and discusses some
      potential areas for future development.

PMID- 17533088
TI  - Pancreatic endocrine tumors.
AB  - Incidental, nonfunctional pancreatic endocrine tumors (PET) are observed with
      increasing frequency. Most are insulinomas. Endoscopic ultrasound with fine
      needle aspiration plays a significant role in the localization and tissue
      diagnosis of PET. Establishing PET behavior as aggressive or indolent remains
      challenging especially preoperatively. Newer techniques including DNA and micro
      RNA analysis may play a role in this arena. Small benign PET may be enucleated or
      removed laparoscopically. Surgery is the mainstay of treating advanced disease
      including those with metastases and Zollinger-Ellison syndrome. The management of
      multiple endocrine neoplasia type 1 continues to be a challenge, including
      treating symptoms, targeted resections, and close observation. Diagnosis,
      management, and prognostication of PET are under evolution and a number of
      changes in these fronts are anticipated.

PMID- 17533089
TI  - Minimally invasive treatment of pancreatic disease.
AB  - Although open surgical procedures remain the standard for both benign and
      malignant diseases of the pancreas, in recent years a wide variety of surgical
      procedures performed on the pancreas have been completed laparoscopically. This
      article reviews the application of minimally invasive surgery to the management
      of both benign and malignant diseases of the pancreas.

PMID- 17533090
TI  - Endoscopic palliation of pancreatic cancer.
AB  - Endoscopic approaches have revolutionized the palliation of advanced pancreatic
      cancer. The ideal management consists of a multidisciplinary approach involving
      surgeons, endoscopists, radiologists, and oncologists. Concurrent advances in the
      fields of interventional radiology and laparoscopic surgical oncology should be
      readdressed and directly compared with endoscopic approaches in randomized
      controlled trials. Exciting novel endoscopic techniques are being developed and
      evaluated; however, these approaches require further validation with randomized
      clinical trials to determine the safety and efficacy when compared with more
      traditional approaches.

PMID- 17533091
TI  - Diagnostic imaging: state of the art or science?

PMID- 17533092
TI  - Modern imaging of the hand, wrist, and forearm.
AB  - A review of the current state of the relevant diagnostic imaging technologies and
      methods and their clinical application in imaging common conditions of the hand,
      wrist, and forearm is presented. Evolving and future imaging technologies are
      also considered.

PMID- 17533093
TI  - Case studies in the diagnosis of upper extremity pain using magnetic resonance
      imaging.
AB  - The diagnosis of upper extremity pain can be a daunting task for the examining
      physician. The differential diagnosis for pain at each level in the upper
      extremity is often extensive and diverse. Quite frequently, the clinical signs
      and symptoms of multiple pathologic conditions are overlapping and nonspecific.
      The decision to treat conservatively or with surgery often depends on the
      magnetic resonance imaging (MRI) findings. MRI's ability to produce multiplanar
      images with excellent soft tissue contrast has made it an indispensable tool for
      diagnosis and treatment planning in patients with upper extremity pain. In most
      instances, MR imaging provides information that all other modalities cannot. This
      is all possible due to an incredible imaging device that creates magnificent
      images painlessly and with no known detrimental biological side effects. This
      article demonstrates only a small number of the possible causes of upper
      extremity pain that can be diagnosed with MR imaging. It is comforting to know
      that the vast majority of pathology causing pain in the upper extremity can be
      visualized with MRI scanning.

PMID- 17533094
TI  - A case of ulnar positive variance found on x-ray.
AB  - A briefcase report is presented that demonstrates the advantage of the
      therapist's viewing of a series of wrist x-rays in guiding the clinical
      management of a patient with an ulnar plus configuration. The positive findings
      revealed on these images facilitated an improved outcome. This case is offered to
      encourage therapists to routinely look at x-rays in their clinical practice.

PMID- 17533095
TI  - Radiography: a review for the rehabilitation professional.
AB  - In the normal course of practice, rehabilitation professionals are not typically
      provided with x-rays or radiology reports. Hand therapists who obtain x-rays or
      reports will glean valuable information about the patient that might otherwise go
      unidentified. Unique details discovered from an x-ray can contribute to improved
      clinical treatment plans and functional outcomes. Radiography is the general term
      used to describe the commonly known imaging procedures of x-ray and fluoroscopy.
      The purposes of this article are to provide the reader with an overview of basic
      radiography terminology and provide information to help better understand the
      typical positions and views used in upper extremity radiography. With this
      knowledge, guidelines for reviewing x-rays will be presented and several examples
      of bony pathology revealed by x-rays will be presented along with several case
      studies.

PMID- 17533096
TI  - Breast imaging in the new millennium: separating the hype from reality.

PMID- 17533097
TI  - Reprint of imaging of the elbow: a review of imaging findings in acute and
      chronic traumatic disorders of the elbow.
AB  - Traumatic injuries of the elbow are frequent in patients of all ages but are
      particularly common in young children and adolescents engaged in normal play and
      athletic competition. Injury may result primarily due to direct trauma or may be
      secondary to transmission of forces through the elbow following a fall on an
      outstretched hand. In middle-aged and older individuals, chronic repetitive
      injuries tend to predominate. In all patients, radiographs remain the initial
      imaging study of choice. Many patients, however, may need advanced cross
      sectional imaging (i.e. MRI, CT, or ultrasound) either at presentation or during
      the course of their treatment and follow-up. This article reviews the imaging
      appearance of common acute and chronic traumatic disorders of the elbow.

PMID- 17533098
TI  - Reprint of diagnostic imaging of the shoulder.

PMID- 17533099
TI  - Reprint of wrist disorders: what should we be looking for with imaging
      techniques?

PMID- 17533101
TI  - Psychological correlates of obese patients seeking surgical or residential
      behavioral weight loss treatment.
AB  - BACKGROUND: The purpose of this study was to gain a better understanding of the
      psychological factors related to obese individuals self-selecting for either a
      residential cognitive-behavioral-based program or surgical treatment program for
      weight loss. METHODS: Two patient samples with a body mass index of > or =35
      kg/m(2) were administered a battery of psychological questionnaires, including
      the Beck Depression Inventory, Binge Eating Scale, and Impact of Weight on
      Quality of Life-Lite, at the evaluation for entry into either a surgical weight
      loss treatment program (n = 76) or cognitive-behavioral-based weight loss
      treatment program (n = 101). RESULTS: No significant difference was found in the
      mean body mass index of the 2 samples. No significant difference was found in the
      self-reported level of depressive symptoms of the 2 samples, with both samples
      obtaining a mean depressive symptom score in the mild range. Surgical treatment
      seekers, however, reported significantly greater emotional eating and attributed
      greater impairment in their quality of life to their weight. CONCLUSION:
      Individuals seeking a surgical approach to weight loss might perceive their
      weight as having a greater negative impact on their life than those selecting a
      residential behavioral lifestyle change approach, even when their weight and
      depressive symptoms are equivalent. Therefore, an individual's own cognitive
      appraisal of the negative consequences of their weight might correlate with their
      treatment choice.

PMID- 17533102
TI  - Quality of life and resolution of co-morbidities in super-obese patients
      remaining morbidly obese after Roux-en-Y gastric bypass.
AB  - BACKGROUND: Not all patients undergoing Roux-en-Y gastric bypass with an initial
      body mass index (BMI) >50 kg/m(2) attain a BMI of <35 kg/m(2) postoperatively. We
      hypothesized that even though many of these patients remain morbidly obese after
      surgery, they still realize an improvement in co-morbidities and quality of life.
      METHODS: Patients who had undergone Roux-en-Y gastric bypass and who had a
      preoperative BMI >50 kg/m(2) and postoperative BMI >35 kg/m(2) were identified.
      The records of 120 patients were reviewed for the presence of diabetes,
      hypertension, hyperlipidemia, and gastroesophageal reflux disease. Patients were
      queried about their use of medications, medical problems, and quality of life.
      RESULTS: The average preoperative and postoperative BMI was 63.2 and 43.7
      kg/m(2). Of the 120 patients, 77 responded to the survey. In the preoperative
      group, the rate of diabetes, hypertension, hyperlipidemia, and gastroesophageal
      reflux disease was 35%, 50.8%, 15%, and 34.2%, respectively. Postoperatively,
      73.8%, 62.3%, 38.9%, and 87.8% of patients had been cured of these co
      morbidities. The change in the incidence of diabetes, hypertension, and
      gastroesophageal reflux disease was significant at P = 0.0014, P = 0.037, and P
      <0.0001, respectively. More than 90% of patients considered themselves to be
      better postoperatively in the areas of overall health and ability to move about;
      80-90% had improved ability to exercise, greater energy levels, more self esteem,
      and an improved physical appearance; 70-80% saw their ability to work and their
      social relationships as improved; and 56% believed their sexual relationships had
      improved. CONCLUSION: Super-obese patients experience significant improvements in
      co-morbidities and quality of life after Roux-en-Y gastric bypass even if their
      BMI remains >35 kg/m(2).

PMID- 17533103
TI  - "Candy cane" Roux syndrome--a possible complication after gastric bypass surgery.
AB  - BACKGROUND: An excessive length of nonfunctional Roux limb proximal to the
      gastrojejunostomy can cause abnormal upper gastrointestinal symptoms after
      gastric bypass surgery. The purpose of this study was to characterize the
      syndrome and provide the practitioner with diagnosis and management options.
      METHODS: We performed a retrospective descriptive review of patients who had
      undergone revisional surgery for "candy cane" Roux syndrome. RESULTS: From 2004
      to 2006, 3 patients underwent revision because of a redundant proximal Roux limb.
      These 3 revisions were performed at 3, 12, and 36 months after the original Roux
      en-Y gastric bypass procedure. The symptoms included regurgitation of food in 2
      patients, reflux in 2, significant weight regain in 1, postprandial pain that was
      relieved after vomiting in 2, persistent nausea in 2, and epigastric fullness in
      2 patients. The symptoms were progressive in all 3 patients. The resected length
      of bowel ranged from 8 to 15 cm. Three different surgeons had performed the
      initial gastric bypass, and a circular stapler had been used for the construction
      of the original gastrojejunostomy in all 3 patients. Resection of the excess Roux
      limb was performed laparoscopically in all cases, and all patients reported
      complete and immediate resolution of their symptoms. CONCLUSION: A long,
      nonfunctional Roux limb tip may cause persistent nausea, postprandial epigastric
      pain, and, even, a lack of satiety. Surgeons should attempt to minimize
      redundancy in the Roux limb during the primary procedure. Additional studies may
      better characterize this possible complication.

PMID- 17533104
TI  - Tomographic features of serous retinal detachment with multilobular dye pooling
      in acute Vogt-Koyanagi-Harada disease.
AB  - PURPOSE: To clarify the morphologic background of serous retinal detachment with
      multilobular dye pooling on fluorescein angiography (FA) in acute Vogt-Koyanagi
      Harada (VKH) disease. DESIGN: Retrospective uncontrolled case series. METHODS:
      setting: Institutional study. study population: Ten eyes of five patients aged 16
      to 52 years (average age, 31 years) with VKH disease who presented with a serous
      retinal detachment. observation procedures: Clinical examination and optical
      coherence tomography (OCT). main outcome measures: Findings on OCT and FA.
      RESULTS: All eyes had multilobular dye pooling with a dark rim on late-phase FA.
      OCT revealed subretinal septa that divided the subretinal space into several
      compartments. The subretinal septum lay on the retinal pigment epithelium (RPE)
      in the foveal area, forming the posterior wall of the subfoveal compartment while
      it detached from the RPE in the perifoveal area, which served as a lateral wall
      between the subfoveal and perifoveal compartments. The dark rims of each area of
      subretinal dye pooling corresponded to the subretinal septa. Soon after steroid
      pulse therapy, the subretinal septa resolved completely in all eyes. CONCLUSION:
      Subretinal septa caused multilobular dye pooling in serous retinal detachment
      associated with acute VKH disease. We assume that the subretinal septa are
      comprised of inflammatory products such as fibrin, which immediately resolve
      after steroid pulse therapy.

PMID- 17533105
TI  - Outcome of early surgery for bilateral congenital cataracts in eyes with
      microcornea.
AB  - PURPOSE: To report the outcome of early surgery for bilateral congenital
      cataracts in eyes with microcornea. DESIGN: Interventional case series. METHODS:
      We retrospectively reviewed 22 eyes of 11 patients with microcorneas who
      underwent early surgery for bilateral congenital cataracts. All patients
      underwent lensectomy and anterior vitrectomy via the limbal approach by 12 weeks
      of age. The corneal diameters at the time of surgery ranged from 7.0 to 9.0 mm.
      The mean age at the time of surgery was 7.7 +/- 3.3 weeks (range, two to 12
      weeks); the follow-up period was 115 +/- 58 months (range, 40 to 199 months).
      Aphakic eyes were corrected with spectacles or contact lenses. Visual acuities
      and the postoperative complications were evaluated periodically. RESULTS: The
      morphologic types of cataract were nuclear (12 eyes), complete (eight eyes), and
      membranous (two eyes). Other preoperative ocular abnormalities included iris
      hypoplasia in 10 eyes and persistent fetal vasculature in three eyes. Systemic
      abnormalities were found in four patients. Postoperative complications occurred
      in 11 eyes (50%), including glaucoma (nine eyes), exudative retinal detachment
      (two eyes), rhegmatogenous retinal detachment, and secondary membrane formation,
      in one eye each. The binocular visual acuity was 20/40 to 20/20 in six patients
      (55%), 20/200 to 20/100 in two patients (18%), and 2/100 or worse in three
      patients (27%) who developed postoperative glaucoma. CONCLUSION: Despite
      microcorneas, favorable visual outcomes were achieved after early surgery in this
      series. However, adequate management of postoperative complications, especially
      glaucoma, is required.

PMID- 17533106
TI  - Long-term results of thin corneas after refractive laser surgery.
AB  - PURPOSE: To report the long-term refractive results of photorefractive
      keratectomy (PRK) and laser in situ keratomileusis (LASIK) in patients with thin
      corneas. DESIGN: A long-term, retrospective, non-randomized follow-up study.
      METHODS: Sixty-three patients (124 eyes) (28 males and 35 females), who had a
      preoperative central corneal thickness (CCT) of less than 500 microns and
      completed at least one year of follow-up examinations after surgery. Thirty-five
      patients (68 eyes) underwent PRK and 28 patients (56 eyes) underwent LASIK.
      RESULTS: Mean preoperative corneal pachymetry was 484.95 +/- 6.65 microm (range,
      470 to 498 microm) and 482.38 +/- 10.73 microm (range, 453 to 499 microm) for
      LASIK and PRK, respectively. No intraoperative complications were found in both
      groups. None of the included eyes developed postrefractive corneal ectasia. The
      mean predictability for the PRK group was 0.08 diopters (D) with a standard
      deviation of 0.40 D (range, -1.38 to 1.00 D), and the mean predictability for the
      LASIK group was 0.14 D with a standard deviation of 0.55 D (range, -1.25 to 1.33
      D). CONCLUSIONS: Refractive laser surgery with LASIK or PRK in patients with thin
      corneas (less than 500 microm) seems to be a safe and predictable technique for
      myopic refractive corrections.

PMID- 17533107
TI  - Noninvasive interference tear meniscometry in dry eye patients with Sjogren
      syndrome.
AB  - PURPOSE: To compare noninvasive tear meniscus height (NI-TMH) using a tear
      interference device in normal subjects and dry eye patients with Sjogren syndrome
      (SS), and to investigate the applicability of this new method before and after
      the punctal occlusion procedure. DESIGN: Prospective case control study. METHODS:
      Tear meniscus was visualized noninvasively using a tear interference device
      (Tearscope plus, Keeler, Windsor, United Kingdom). Tear interference image was
      captured with digital video camera (SP-321, JFC Sales Plan Co, Tokyo, Japan)
      attached to the slit-lamp. Lower lid margin NI-TMH was measured using image
      analysis software. NI-TMH of 28 eyes from 17 normal subjects and 46 eyes from 27
      aqueous tear deficiency (ATD) dry eye patients with SS were compared. The change
      of NI-TMH three weeks after the successful punctal occlusion was examined in 11
      eyes of eight dry eye subjects. RESULTS: Tear meniscus was well visualized with
      the tear interference device in all cases. Lower lid margin NI-TMH was 0.22 +/-
      0.065 mm in normal subjects, and 0.13 +/- 0.042 mm in SS subjects, respectively
      (P < .0001). After the punctal occlusion, lower lid margin NI-TMH increased
      significantly from 0.12 +/- 0.026 mm to 0.42 +/- 0.21 mm (P = .001). CONCLUSIONS:
      NI-TMH was substantially lower in SS subjects and also significantly improved
      after punctal occlusion. This method is expected to be helpful in the diagnosis
      and in the evaluation of the efficacy of punctal occlusion in ATD dry eyes such
      as SS.

PMID- 17533108
TI  - Ocular dominance diagnosis and its influence in monovision.
AB  - PURPOSE: To analyze the response of normal emmetropic subjects to different
      ocular dominance tests and to analyze the influence of this response in
      surgically induced monovision. DESIGN: A prospective study of diagnostic accuracy
      was carried out to analyze the different tests to determine ocular dominance,
      without a gold standard test. METHODS: Nine different tests were carried out in a
      group of 51 emmetropic subjects to determine both motor and sensory ocular
      dominance. For analysis, patients were divided into two groups according to age.
      Normal ophthalmologic examination results were the inclusion requirement, with
      normal binocular vision and good stereoacuity. RESULTS: A significant percentage
      of uncertain or ambiguous results in all tests performed was found, except in the
      hole-in-card and kaleidoscope tests. When the tests were compared, two by two,
      the correlation or equivalence found was low and was much lower if tests were
      compared three by three. CONCLUSIONS: No clear ocular dominance was found in most
      studied subjects; instead, there must be a constant alternating balance between
      both eyes in most emmetropic persons, but not in those with pathologic features.
      This fact would explain the great variability both between and within different
      kinds of tests. Also, it would establish that the monovision technique is well
      tolerated in most patients, with unsuccessful results only in those patients with
      strong or clear dominance. Consequently, it seems appropriate to evaluate
      patient's dominance before monovision surgery to exclude those individuals with
      clear dominance.

PMID- 17533109
TI  - Cleavage of spike protein of SARS coronavirus by protease factor Xa is associated
      with viral infectivity.
AB  - The spike (S) protein of SARS coronavirus (SARS-CoV) has been known to recognize
      and bind to host receptors, whose conformational changes then facilitate fusion
      between the viral envelope and host cell membrane, leading to viral entry into
      target cells. However, other functions of SARS-CoV S protein such as proteolytic
      cleavage and its implications to viral infection are incompletely understood. In
      this study, we demonstrated that the infection of SARS-CoV and a pseudovirus
      bearing the S protein of SARS-CoV was inhibited by a protease inhibitor Ben-HCl.
      Also, the protease Factor Xa, a target of Ben-HCl abundantly expressed in
      infected cells, was able to cleave the recombinant and pseudoviral S protein into
      S1 and S2 subunits, and the cleavage was inhibited by Ben-HCl. Furthermore, this
      cleavage correlated with the infectivity of the pseudovirus. Taken together, our
      study suggests a plausible mechanism by which SARS-CoV cleaves its S protein to
      facilitate viral infection.

PMID- 17533110
TI  - RNA mutations of prox1 detected in human esophageal cancer cells by the shifted
      termination assay.
AB  - We have recently reported a novel finding that a candidate tumor suppressor gene
      prox1 suffered adenosine-to-inosine (A-to-I) RNA mutation without genomic
      mutation in a subset of human cancer cells and lost its function. Hence,
      screening of mutations in both cDNA and genomic DNA could be important in the
      analysis of causes for cancers. Here, we applied a sensitive, accurate, and
      simple method, called shifted termination assay (STA) for detection of an A-to-I
      RNA mutation (R334G) in prox1. We prepared PCR-amplified samples containing the
      target base of RNA mutation from cDNAs and genomic DNAs of various cell lines and
      clinical samples, to demonstrate that the STA method can be used to identify not
      only genomic mutations but also RNA mutations more effectively compared to
      sequencing. By means of STA, we found prox1 R334G RNA mutations but not genomic
      DNA mutations in 4 of 8 cases of esophageal cancers. This method can help us to
      detect RNA mutation effectively and progress research of a potential oncogenic
      principle.

PMID- 17533111
TI  - The GLK1 'regulon' encodes disease defense related proteins and confers
      resistance to Fusarium graminearum in Arabidopsis.
AB  - Overexpression (OE) was used to study the role of the Arabidopsis Golden2-like
      (GLK1) transcriptional activator in regulating gene expression. Affymetrix Gene
      Chip and RT-PCR analyses indicated that GLK1 OE in Arabidopsis reprogrammed gene
      expression networks to enhance a high constitutive expression of genes encoding
      disease defense related proteins. These include PR10, isochorismate synthase,
      antimicrobial peptides, glycosyl hydrolases, MATE efflux and other genes
      associated with pathogen response and detoxification. However, PR1, an indicator
      of systemic acquired resistance (SAR), was downregulated in GLK1 OE. GLK1 OE in
      Arabidopsis confers resistance to Fusarium graminearum, a broad host pathogen
      responsible for major losses in cereal crops. This is the first identification of
      the GLK1 'regulon' and a novel role for GLK1 in plant defense, suggesting its
      potential use for providing disease resistance in crop plants.

PMID- 17533112
TI  - Direct selection of RNA beacon aptamers.
AB  - A method for the direct selection of RNA molecules that can be easily converted
      into beacon aptamers is presented. Beacon aptamers are fluorescently labeled
      nucleic acids that signal the presence of a specific ligand through changes in
      fluorescence intensity. Typically, ligand binding causes an increase in
      fluorescence intensity by inducing a conformational change that separates a
      fluorophore/quencher pair. The method presented here simultaneously selects for
      ligand binding and induction of an appropriate conformational change. The method
      was tested by selecting RNA molecules that can detect the aminoglycoside
      antibiotic tobramycin. After 14 rounds of selection, two sequence families
      emerged. Upon conversion into beacon aptamers, representatives of the two
      selected sequence families specifically detected tobramycin, while a negative
      control RNA that did not survive the selection protocol did not function as a
      tobramycin beacon aptamer.

PMID- 17533113
TI  - Short hairpin RNA causes the methylation of transforming growth factor-beta
      receptor II promoter and silencing of the target gene in rat hepatic stellate
      cells.
AB  - Small interfering RNA (siRNA) induces transcriptional gene silencing (TGS) in
      plant and animal cells. RNA dependent DNA methylation (RdDM) accounts for TGS in
      plants, but it is unclear whether siRNA induces RdDM in mammalian cells. To
      determine whether stable expression of short hairpin siRNA (shRNA) induces DNA
      methylation in mammalian cells, we transduced rat hepatic stellate SBC10 cells
      with lentiviral vectors which encode an U6 promoter-driven shRNA expression
      cassette homologous to the transforming growth factor-beta receptor (TGFbetaRII)
      promoter region. Sequencing analysis of bisulfite-modified genomic DNA showed the
      methylation of cytosine residues both in CpG dinucleotides and non-CpG sites
      around the target region of the TGFbetaRII promoter in SBC10 cells transduced
      with the promoter-targeting lentiviral vector. In these cells, real-time RT-PCR
      showed a decrease in TGFbetaRII mRNA levels which were reversed by treatment with
      5-aza-2-deoxycytidine. Our results demonstrate that recombinant lentivirus
      mediated shRNA delivery resulted in the methylation of the homologous promoter
      area in mammalian cells, and this approach may be used as a tool for
      transcriptional gene silencing by epigenetic modification of mammalian cell
      promoters.

PMID- 17533114
TI  - Cryoprotectant delivery and removal from murine insulinomas at vitrification
      relevant concentrations.
AB  - Development of optimal cryopreservation protocols requires delivery and removal
      of cryoprotective agents (CPAs) in such a way that negative osmotic and cytotoxic
      effects on cells are minimized. This is especially true for vitrification, where
      high CPA concentrations are employed. In this study, we report on the
      determination of cell membrane permeability parameters for water (L(p)) and
      solute (P(s)), and on the design and experimental verification of CPA addition
      and removal protocols at vitrification-relevant concentrations for a murine
      insulinoma cell line, betaTC-tet cells. Using membrane permeability values and
      osmotic tolerance limits, mathematical modeling and computer simulations were
      used to design CPA addition and removal protocols at high concentrations. The
      cytotoxic effects of CPAs were also evaluated. Cells were able to tolerate the
      addition and removal of 2.5M dimethyl sulfoxide (DMSO) and 2.5M 1,2 propanediol
      (PD) in single steps, but required multi-step addition and removal with 3.0M
      DMSO, 3.0M PD, and a vitrification-relevant concentration of 3.0M DMSO+3.0M PD.
      Cytotoxicity studies revealed that betaTC-tet cells were able to tolerate the
      presence of single component 6.0M DMSO and 6.0M PD and to a lesser extent 3.0M
      DMSO+3.0M PD. These results determine the time and concentration domain of CPA
      exposure that cells can tolerate and are essential for designing cryopreservation
      protocols for free cells as well as cells in engineered tissues.

PMID- 17533116
TI  - The role of TRPV1 receptors in the antinociceptive effect of anandamide at spinal
      level.
AB  - While it is well known that the endogenous cannabinoid receptor ligand anandamide
      also activates the transient receptor potential vanilloid1 (TRPV1) receptors,
      there has been no in vivo study indicating the role of the TRPV1 receptors in the
      antinociceptive effect of anandamide at spinal level. The goal of this study was
      to determine the effect of inhibition of TRPV1 receptors by capsazepine on the
      antinociceptive potency of anandamide after intrathecal administration.
      Anandamide alone (1, 30 or 100 microg) dose-dependently decreased carrageenan
      induced thermal hyperalgesia, however, the highest dose caused temporary
      excitation and vocalization, suggesting the pain-inducing potential of
      anandamide. Capsazepine (10 or 20 microg) by itself did not change the pain
      sensitivity markedly, but the lower dose increased it, and the higher dose
      decreased the antinociceptive effect of 30 microg anandamide. Furthermore, both
      doses of capsazepine decreased the efficacy of the largest dose of anandamide.
      These results show that TRPV1 receptor activation plays a substantial role in the
      antinociceptive effects of anandamide at spinal level. The effect of the
      inhibition on TRPV1 receptors depended on the dose applied. We presume that
      coactivation of the cannabinoid and TRPV1 receptors by anandamide provides
      elevated antinociception through the release of antinociceptive endogenous
      ligands at spinal level.

PMID- 17533117
TI  - Peripheral and central components of habituation of heat pain perception and
      evoked potentials in humans.
AB  - For the neurophysiological examination of nociceptive pathways, contact-heat
      evoked potentials (contact-heat EPs) are elicited by repetitive brief noxious
      heat stimuli. Suppression of heat responses in primary nociceptive neurons during
      repetitive stimulation has been shown in animal models in vivo and in vitro. We
      now investigated whether heat pain and contact-heat EPs in humans display
      equivalent signs of habituation. Heat pain and EPs were elicited in 16 volunteers
      with a contact thermode (30 degrees Cs(-1)). Heat pulses at three intensities
      (pain threshold, moderate noxious and maximum available) were applied to the
      right forearm either by moving the thermode after each pulse to variable
      locations or when fixed to one location (inter-stimulus intervals 8-10s). Contact
      heat EPs consisted of an early negativity in temporal leads (N1), followed by a
      biphasic response at the vertex (N2-P2). Pain ratings and contact-heat EPs (N1
      and N2-P2 components) displayed significant temperature dependence. N2-P2
      correlated positively with ratings. With stimulation at variable locations, both
      measures slowly decreased with time constants tau of 2 min (ratings) and 12 min
      (EPs). With stimulation at a fixed location, habituation was much faster for
      both, ratings (tau=10s) and EPs (tau=33 s). As a consequence, both measures were
      significantly reduced (p<0.005) leading to a rightward shift of the stimulus
      response function by 5 degrees C. In conclusion, human heat pain perception and
      contact-heat EPs display signs of rapid habituation when stimulation is
      restricted to a fixed location and thus, reflect fatigue of peripheral
      nociceptive neurons. Habituation within the central nervous system is slower and
      less pronounced.

PMID- 17533118
TI  - Offset analgesia: a temporal contrast mechanism for nociceptive information.
AB  - Temporal filtering of afferent information is an intrinsic component of the
      processing of numerous types of sensory information. To date, no temporal
      filtering mechanism has been identified for nociceptive information. The
      phenomenon of offset analgesia, the disproportionately large decrease in
      perceived pain following slight decreases in noxious thermal intensity, however,
      suggests the existence of such a mechanism. To test the hypothesis that a
      temporal filtering mechanism is engaged during noxious stimulus offset, subjects
      rated heat pain intensity while stimulus fall rates were varied from -0.5 to -5.0
      degrees C/s. In the absence of a temporal filtering mechanism, pain intensity
      would be expected to decrease in direct proportion to the stimulus fall rate.
      However, psychophysical fall rates were considerably faster than stimulus fall
      rates, such that subjects reported no pain while stimulus temperatures were
      clearly within the noxious range (47.2 degrees C). In addition, paired noxious
      stimuli were presented simultaneously to determine if offset analgesia evoked by
      one stimulus could inhibit pain arising from a separate population of primary
      afferent neurons. Pain ratings were significantly lower than those reported from
      two constant 49 degrees C stimuli when offset analgesia was induced proximal to,
      but not distal to, a second noxious stimulus. These asymmetric spatial
      interactions are not readily explained by peripheral mechanisms. Taken together,
      these findings indicate that offset analgesia is mediated in part by central
      mechanisms and reflect a temporal filtering of the sensory information that
      enhances the contrast of dynamic decreases in noxious stimulus intensity.

PMID- 17533119
TI  - Spatial performance in a complex maze is associated with persistent long-term
      potentiation enhancement in mouse hippocampal slices at early training stages.
AB  - Long-term potentiation (LTP) and long-term depression (LTD) are principal
      reflections of synaptic plasticity that have been implicated in learning and
      memory. We have previously shown that spatial learning in a newly validated
      complex maze is accompanied by depression of hippocampal CA1 synaptic activity in
      hippocampal slices of trained mice ("behavioral LTD"). In the present study, we
      investigated whether behavioral LTD is accompanied by alterations of subsequent
      LTP induced by high-frequency stimulation (HFS). Moreover, we were interested in
      the time course of such alterations in relation to training stage. Animals
      underwent 1, 2, and 8 days of spatial training in the complex maze, respectively.
      Hippocampal slices were taken 24 h after the last training session. We found a
      simultaneous decrease of basal synaptic response and increase of HFS induced LTP
      magnitude compared with slices of untrained animals. Synaptic plasticity was not
      influenced by repeated running wheel exercise in an additional control group
      without spatial learning. The mentioned alterations occurred already after day 2
      of maze exploration parallel to the most pronounced improvement of behavioral
      performance but did not change thereafter until day 8 despite further learning
      progress. They were also found when animals were trained for 2 days and kept at
      rest for a subsequent 6 days. In conclusion, spatial learning may be reflected by
      distinct and persistent measurable alterations of synaptic plasticity in
      hippocampal CA1 neurons at early training stages.

PMID- 17533120
TI  - Licensing regulators Geminin and Cdt1 identify progenitor cells of the mouse CNS
      in a specific phase of the cell cycle.
AB  - Nervous system formation integrates control of cellular proliferation and
      differentiation and is mediated by multipotent neural progenitor cells that
      become progressively restricted in their developmental potential before they give
      rise to differentiated neurons and glial cells. Evidence from different
      experimental systems suggests that Geminin is a candidate molecule linking
      proliferation and differentiation during nervous system development. We show here
      that Geminin and its binding partner Cdt1 are expressed abundantly by neural
      progenitor cells during early mouse neurogenesis. Their expression levels decline
      at late developmental stages and become undetectable upon differentiation.
      Geminin and Cdt1 expressing cells also express Sox2 while no overlap is detected
      with cells expressing markers of a differentiated neuronal phenotype. A fraction
      of radial glial cells expressing RC2 and Pax6 are also immunoreactive for Geminin
      and Cdt1. The majority of the Geminin and Cdt1 expressing cell populations
      appears to be distinct from fate-restricted precursor cells expressing Mash1 or
      Neurogenin2. Bromo-deoxy-uridine (BrdU) incorporation experiments reveal a cell
      cycle specific expression in neural progenitor cells, with Geminin being present
      from S to M phase, while Cdt1 expression characterizes progenitor cells in G1
      phase. Furthermore, in vitro differentiation of adult neurosphere cultures shows
      downregulation of Geminin/Cdt1 in the differentiated state, in line with our data
      showing that Geminin is present in neural progenitor cells of the CNS during
      mouse embryogenesis and adulthood and becomes downregulated upon cell fate
      specification and differentiation. This suggests a role for Geminin in the
      formation and maintenance of the neural progenitor cells.

PMID- 17533122
TI  - Roles for flagellar stators in biofilm formation by Pseudomonas aeruginosa.
AB  - While Pseudomonas aeruginosa has only a single flagellum, its genome encodes two
      flagellar stators, called MotAB and MotCD. Here we report that despite no
      apparent alterations in swimming motility, mutations in either the MotAB or the
      MotCD stator render the strains defective for biofilm formation in both static
      and flow cell systems. Our data suggest distinct roles for the stators in early
      biofilm formation, with both the MotAB and MotCD stators playing a role in
      initial polar attachment of the bacterial cell to the surface (reversible
      attachment) and the MotAB stator also participating in the downstream adherence
      event of irreversible attachment. We also show that the initial polar attachment
      of P. aeruginosa to two different abiotic surfaces occurs largely at the
      flagellated end of the cell, a finding that should help develop models for early
      attachment events. Interestingly, in flowing conditions, a mutation in either
      stator alone revealed a more severe biofilm defect than mutating both stators or
      mutating the flagellum. Our data suggest that defects in biofilm formation
      observed for the stator mutants may be in part due to impacting flagellar
      reversal rates.

PMID- 17533121
TI  - Cerebral hemodynamics and oxygenation after serial CSF drainage in infants with
      PHVD.
AB  - The aim of our study was to assess consecutive changes in cerebral oxygenation
      and hemodynamics after serial cerebrospinal fluid (CSF) drainage from a
      subcutaneous ventricular catheter reservoir (SVCR) in infants with PHVD. Infants
      with PHVD were studied during CSF drainage from a SVCR on the day of SVCR
      placement, half a week and one week after SVCR placement. Changes in cHbD and CBV
      were assessed using near infrared spectrophotometry. Time averaged peak flow
      velocity (TAPFV), end diastolic flow velocity (EDFV), peak systolic flow velocity
      (PSFV) and pulsatility index (PI) were measured before (baseline) and after CSF
      drainage using Doppler ultrasound. Longitudinal data analysis was performed using
      linear mixed models. Seven patients (GA 26.7-40.4 weeks, BW 800-4575 g) were
      studied. CSF drainage resulted in a statistically significant increase in CBV
      during each measurement. The change in CBV was maximal on the day of SVCR
      placement. A significant increase in cHbD and EDFV, and decrease in PI was
      observed after CSF drainage only on the day of SVCR placement. Baseline values of
      all Doppler variables improved consecutively after serial CSF removal in the
      first week after SVCR placement. Frequent CSF drainage results in consecutive
      improvement of cerebral perfusion and oxygenation in infants with PHVD.

PMID- 17533123
TI  - Nanoparticles based on the complex of chitosan and polyaspartic acid sodium salt:
      preparation, characterization and the use for 5-fluorouracil delivery.
AB  - New nonstoichiometric polyelectrolyte complex nanoparticles were prepared based
      on chitosan (CS) and polyaspartic acid sodium salt (PAsp). The physicochemical
      properties of the complexes were investigated by means of turbidity, dynamic
      light scattering, transmission electron microscopy and zeta potential. The
      results indicated that the slow dropwise addition of chitosan into PAsp allowed
      to elaborate either anionic or cationic particles in the size range of 85-300 nm
      with proper CS and PAsp unit molar ratios. Investigation of structural changes
      during the addition of CS revealed that the microstructure of the nanoparticles
      depended strongly on the unit molar ratio of CS to PAsp. Nanoparticles containing
      a hydrophilic drug, 5-fluorouracil (5FU), were prepared by mixing and absorption
      method. In vitro and in vivo experiment indicated that the drug-loaded CS-PAsp
      nanoparticles presented a sustained release of 5FU compared to the 5FU solution
      and the areas under curve (AUC) were increased by about four times.

PMID- 17533124
TI  - In vitro cytotoxicity study on platinum (II) complexes with epoxysuccinates as
      leaving groups.
AB  - A series of novel cisplatin-type platinum complexes were designed, characteristic
      of epoxysuccinates as leaving groups. The pertinent compounds were prepared and
      characterized by IR, (1)H NMR, and ESI-MS spectra with elementary analyses. The
      in vitro cytotoxic activities of compounds toward SPC-A1 human lung
      adenocarcinoma cell line and BGC823 human stomach adenocarcinoma cell line were
      determined. Biological tests have confirmed that complexes containing 4R,5R-DMID
      [abbreviation of (4R,5R)-4,5-bis (aminomethyl)-2-isopropyl-1,3-dioxolane] as
      carrier ligands have greater cytotoxicity toward tumor cells than the
      corresponding compounds with other carrier ligands. Most platinum complexes with
      trans-epoxysuccinates usually have higher cytotoxicity than those with cis
      epoxysuccinates. Complex 4a shows the most effective among those tested platinum
      complexes in both cell lines, and its cytotoxicity approached that of cisplatin.

PMID- 17533125
TI  - Co-crystal structure guided array synthesis of PPARgamma inverse agonists.
AB  - PPARgamma-activating thiazolidinediones and carboxylic acids such as farglitazar
      exert their anti-diabetic effects in part in PPARgamma rich adipose. Both pro-
      and anti-adipogenic PPARgamma ligands promote glucose and lipid lowering in
      animal models of diabetes. Herein, we disclose representatives of an array of 160
      farglitazar analogues with atypical inverse agonism of PPARgamma in mature
      adipocytes.

PMID- 17533126
TI  - Arylpropanolamines: selective beta3 agonists arising from strategies to mitigate
      phase I metabolic transformations.
AB  - Utilization of N-substituted-4-hydroxy-3-methylsulfonanilidoethanolamines 1 as
      selective beta(3) agonists is complicated by their propensity to undergo
      metabolic oxidative N-dealkylation, generating 0.01-2% of a very potent alpha(1)
      adrenergic agonist 2. A summary of the SAR for this hepatic microsomal conversion
      precedes presentation of strategies to maintain the advantages of chemotype 1
      while mitigating the consequences of N-dealkylation. This effort led to the
      identification of 4-hydroxy-3-methylsulfonanilidopropanolamines 15 for which the
      SAR for the unique stereochemical requirements for binding to the beta adrenergic
      receptors culminated in the identification of the potent, selective beta(3)
      agonist 15f.

PMID- 17533127
TI  - Potent macrocyclic antagonists to the motilin receptor presenting novel unnatural
      amino acids.
AB  - Novel, potent small molecule motilin receptor antagonists are described. These
      peptidomimetic macrocycles are composed of a tripeptide cyclized backbone-to
      backbone with a nonpeptidic tether and bear new unnatural amino acids containing
      basic side chains.

PMID- 17533128
TI  - Anti-AIDS agents 72. Bioisosteres (7-carbon-DCKs) of the potent anti-HIV lead
      DCK.
AB  - Three 9,10-di-O-(-)-camphanoyl-7,8,9,10-tetrahydro-benzo[h]chromen-2-one (7
      carbon-DCK) analogs (3a-c) were synthesized and evaluated for inhibition of HIV-1
      replication in H9 lymphocytes. All three new carbon bioisosteres of the anti-HIV
      lead DCK showed anti-HIV activity. Compound 3a had an EC(50) value of 0.068
      microM, which was comparable to that of DCK in the same assay. The preliminary
      results indicated that 7-carbon-DCK analogs merit attention as potential HIV-1
      inhibitors for further development into clinical trials candidates.

PMID- 17533129
TI  - Musk-antibody positive myasthenia gravis presenting with isolated neck extensor
      weakness.
AB  - Dropped head sign is characterized by the gradual forward sagging of the head due
      to weakness of neck extensor muscles. This may be a prominent sign of several
      neuromuscular disorders and may be an isolated feature of myasthenia gravis (MG).
      We describe a patient with isolated neck extensor weakness, eletrophysiological
      findings suggesting myasthenia gravis and positive MuSK antibodies. This case
      supports that finding anti-MuSK antibodies may be extremely helpful in dropped
      head patients and negative acetylcholine receptor antibodies especially if needle
      EMG does not reveal myopathic or neurogenic patterns.

PMID- 17533130
TI  - Hand versus mouth for call-bell activation by DMD and Becker patients.
AB  - Severe hand dysfunction is common in patients with Duchenne muscular dystrophy
      (DMD) and may preclude the use of conventional call-bells. We prospectively
      evaluated a call-bell with two hand-controlled interfaces (push-button and key
      pinch) and two mouth-controlled interfaces (sip-or-puff) in 32 consecutive DMD
      and Becker patients. Patients called intentionally 348 times, using the sip-or
      puff device 237 times and the hand-controlled interfaces 147 times. Use of the
      hand-controlled interfaces correlated with key-pinch strength (R=0.366; P=0.04).
      Six patients reported being unable to call with the hand interfaces and five
      patients reported temporary call failure due to inaccessibility of the sip-or
      puff interface. Ease-of-use scores on a visual analogue scale were best for puff,
      followed by sip then key-pinch interrupter and push-button (8.7+/-2.1, 7.5+/-2.7,
      6.2+/-3.9, and 0.5+/-2.0 respectively; ANOVA: P<0.00001). In conclusion sip-or
      puff devices should be considered more often to provide neuromuscular patients
      with greater independence.

PMID- 17533131
TI  - Structure-activity relationships of novel N-acyloxy-1,4-dihydropyridines as P
      glycoprotein inhibitors.
AB  - Series of novel N-acyloxy-1,4-dihydropyridines have been synthesized and
      evaluated as P-glycoprotein inhibitors in an in vitro assay to estimate their
      potential to act as multidrug resistance modulators in cancer cells. Structure
      activity relationships are discussed and prove a significant and regiospecific
      influence of certain functional groups.

PMID- 17533132
TI  - Antimitotic activities of 2-phenylindole-3-carbaldehydes in human breast cancer
      cells.
AB  - Small molecules such as indoles are attractive as inhibitors of tubulin
      polymerization. Thus a number of 2-phenylindole-3-carbaldehydes with lipophilic
      substituents in both aromatic rings was synthesized and evaluated for antitumor
      activity in MDA-MB 231 and MCF-7 breast cancer cells. Some 5-alkylindole
      derivatives with a 4-methoxy group in the 2-phenyl ring strongly inhibit the
      growth of breast cancer cells with IC(50) values of 5-20nM. Their action can be
      rationalized by the cell cycle arrest in G(2)/M phase due to the inhibition of
      tubulin polymerization.

PMID- 17533133
TI  - Impaired mutagenic activities of MPDP(+) (1-methyl-4-phenyl-2,3
      dihydropyridinium) and MPP(+) (1-methyl-4-phenylpyridinium) due to their
      interactions with methylxanthines.
AB  - MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) is a neurotoxin causing
      symptoms that resemble those observed in patients suffering from Parkinson's
      disease. However, in animal or human organisms, MPTP is converted to MPDP(+) (1
      methyl-4-phenyl-2,3-dihydropyridinium) and further to MPP(+) (1-methyl-4
      phenylpyridinium); the latter compound is the actual neurotoxin. In this report,
      we demonstrate that MPDP(+) and MPP(+) can form stacking complexes with
      methylxanthines (caffeine and penthoxifylline), which leads to significant
      impairment of the biological activity of these toxins (as measured by their
      mutagenicity).

PMID- 17533134
TI  - Computational modeling tools for the design of potent antimalarial
      bisbenzamidines: overcoming the antimalarial potential of pentamidine.
AB  - Malaria is nowadays a worldwide and serious problem with a significant social,
      economic, and human cost, mainly in developing countries. In addition, the
      emergence and spread of resistance to existing antimalarial therapies deteriorate
      the global malaria situation, and lead thus to an urgent need toward the design
      and discovery of new antimalarial drugs. In this work, a QSAR predictive model
      based on GETAWAY descriptors was developed which is able to explain with, only
      three variables, more than 77% of the variance in antimalarial potency and
      displays a good internal predictive ability (of 73.3% and 72.9% from leave-one
      out cross-validation and bootstrapping analyses, respectively). The performance
      of the proposed model was judged against other five methodologies providing
      evidence of the superiority of GETAWAY descriptors in predicting the antimalarial
      potency of the bisbenzamidine family. Moreover, a desirability analysis based on
      the final QSAR model showed that to be a useful way of selecting the predictive
      variable level necessary to obtain potent bisbenzamidines. From the proposed
      model it is also possible to infer that elevated high atomic
      masses/polarizabilities/van der Waals volumes could play a
      negative/positive/positive role in the molecular interactions responsible for the
      desired drug conformation, which is required for the optimal binding to the
      macromolecular target. The results obtained point out that our final QSAR model
      is statistically significant and robust as well as possessing a high predictive
      effectiveness. Thus, the model provides a feasible and practical tool for looking
      for new and potent antimalarial bisbenzamidines.

PMID- 17533135
TI  - Highly efficient and selective enrichment of phosphopeptides using porous anodic
      alumina membrane for MALDI-TOF MS analysis.
AB  - Because of its good biocompatibility, high surface-to-volume ratio, and distinct
      surface electrical properties, porous anodic alumina (PAA) membrane has been used
      to selectively enrich phosphopeptides from a mixture of synthetic peptides and
      tryptic digest product of beta-casein by a direct MALDI-TOF MS analysis. As we
      reported previously, PAA membrane has strong incorporation ability to the
      phosphate anion. Herein, we describe the application of PAA membrane as a
      selective sampling absorbent for phosphopeptides. The PAA membrane could enrich
      phosphopeptides with high efficiency and selectivity; for example, the tryptic
      digest product of beta-casein at a concentration as low as 4 x 10(-9) M can be
      satisfactorily detected. Compared to that from the nonenriching peptide mixture,
      the MS signal of the phosphorylated peptides enriched by the PAA membrane is
      remarkably improved. In addition, acidic peptides have insignificant influence on
      the enriching process. Results show that the adsorption of phosphate anions on
      the PAA membrane plays a determining role in achieving highly selective enriching
      capacity toward phosphopeptides. The feasibility of PAA membranes as specific
      absorbents for phosphopeptides is also demonstrated.

PMID- 17533136
TI  - Mass spectral behavior of the hydrolysis products of sesqui- and oxy-mustard type
      chemical warfare agents in atmospheric pressure chemical ionization.
AB  - Bis(2-hydroxyethylthio)alkanes and bis(2-hydroxyethylthioalkyl)ethers are
      important biological and environmental degradation products of sulfur mustard
      analogs known as sesqui- and oxy-mustards. We used atmospheric pressure chemical
      ionization mass spectrometry (APCI MS) to acquire characteristic spectra of these
      compounds in positive and negative ionization modes. Positive APCI mass spectra
      exhibited [M + H](+); negative APCI MS generated [M + O(2)](-), [M - H](-), and
      [M - 3H](-); and both positive and negative APCI mass spectra contained fragment
      ions due to in-source collision-induced dissociation. Product ion scans confirmed
      the origin of fragment ions observed in single-stage MS. Although the spectra of
      these compounds were very similar, positive and negative APCI mass spectra of the
      oxy-mustard hydrolysis product, bis(2-hydroxyethylthiomethyl)ether, differed from
      the spectra of the other compounds in a manner that suggested a rearrangement to
      the sesqui-mustard hydrolysis product, bis(2-hydroxyethylthio)methane. We
      evaluated the [M + O(2)](-) adduct ion for quantification via liquid
      chromatography-MS/MS in the multiple-reaction monitoring (MRM) mode by
      constructing calibration curves from three precursor/product ion transitions for
      all the analytes. Analytical figures of merit generated from the calibration
      curves indicated the stability and suitability of these transitions for
      quantification at concentrations in the low ng/mL range. Thus, we are the first
      to propose a quantitative method predicated on the measurement of product ions
      generated from the superoxide adduct anion of the sesqui-and oxy-mustard
      hydrolysis products.

PMID- 17533138
TI  - Expression in Escherichia coli, refolding and crystallization of Aspergillus
      niger feruloyl esterase A using a serial factorial approach.
AB  - Hydrolysis of plant biomass is achieved by the combined action of enzymes
      secreted by microorganisms and directed against the backbone and the side chains
      of plant cell wall polysaccharides. Among side chains degrading enzymes, the
      feruloyl esterase A (FAEA) specifically removes feruloyl residues. Thus, FAEA has
      potential applications in a wide range of industrial processes such as paper
      bleaching or bio-ethanol production. To gain insight into FAEA hydrolysis
      activity, we solved its crystal structure. In this paper, we report how the use
      of four consecutive factorial approaches (two incomplete factorials, one sparse
      matrix, and one full factorial) allowed expressing in Escherichia coli, refolding
      and then crystallizing Aspergillus niger FAEA in 6 weeks. Culture conditions
      providing the highest expression level were determined using an incomplete
      factorial approach made of 12 combinations of four E. coli strains, three culture
      media and three temperatures (full factorial: 36 combinations). Aspergillus niger
      FAEA was expressed in the form of inclusion bodies. These were dissolved using a
      chaotropic agent, and the protein was purified by affinity chromatography on Ni
      column under denaturing conditions. A suitable buffer for refolding the protein
      eluted from the Ni column was found using a second incomplete factorial approach
      made of 96 buffers (full factorial: 3840 combinations). After refolding, the
      enzyme was further purified by gel filtration, and then crystallized following a
      standard protocol: initial crystallization conditions were found using commercial
      crystallization screens based on a sparse matrix. Crystals were then optimized
      using a full factorial screen.

PMID- 17533137
TI  - Pulsed large volume injection gas chromatography coupled with electron-capture
      negative ionization quadrupole mass spectrometry for simultaneous determination
      of typical halogenated persistent organic pollutants.
AB  - A pulsed large-volume injection gas chromatography coupled with electron-capture
      negative ionization quadrupole mass spectrometry (pLVI-GC/ECNI-qMS) was developed
      for the simultaneous determination of typical halogenated persistent organic
      pollutants (H-POPs). By monitoring the characteristic ions of large mass-to
      charge ratio (m/z) for each of the H-POPs rather than the chlorine and/or bromine
      ions, this method avoided the possible interferences arising from the H-POPs
      themselves and from complex matrices encountered frequently in current GC/qMS
      methods; and allowed, on the other hand, the use of (13)C-labeled and
      perdeuterated analogues as internal standards for reliable quantification. pLVI
      up to 120 microL improved the instrumental detection limits down to pg-fg mL(-1),
      comparable to or lower than those obtained by the recognized GC/high-resolution
      MS methods reported so far. The H-POPs including 12 polybrominated diphenyl
      ethers, 1 polybrominated biphenyl, 10 polychlorinated biphenyls (PCBs), 4
      hexachlorocyclohexane isomers, and hexachlorobenzene were involved in this study.
      The method developed demonstrated good linearity (r(2) = 0.9904-0.9999) within
      0.5 to 50,000 pg mL(-1) for PCBs and 0.05 to 5000 pg mL(-1) for other H-POPs, and
      was satisfactory in terms of both repeatability (0.07%-2.2%) and reproducibility
      (2.1%-8.4%). It was validated by analyzing a NIST standard reference material SRM
      1946 of Lake Superior fish tissue with low 0.01 to 63 pg g(-1) method detection
      limits, and successfully applied to the determination of the H-POPs in five
      reference materials of different matrices.

PMID- 17533139
TI  - Understanding umbilical cord blood banking: what women need to know before
      deciding.

PMID- 17533140
TI  - Pre-reflective self-as-subject from experiential and empirical perspectives.
AB  - In the first part of this paper I characterize a minimal form of self
      consciousness, namely pre-reflective self-consciousness. It is a constant
      structural feature of conscious experience, and corresponds to the consciousness
      of the self-as-subject that is not taken as an intentional object. In the second
      part, I argue that contemporary cognitive neuroscience has by and large missed
      this fundamental form of self-consciousness in its investigation of various forms
      of self-experience. In the third part, I exemplify how the notion of pre
      reflective self-awareness can be of relevance for empirical research. In
      particular, I propose to interpret processes of sensorimotor integration in light
      of the phenomenological approach that allows the definition of pre-reflective
      self-consciousness.

PMID- 17533141
TI  - Measurement of multilamellar onion dimensions under shear using frequency domain
      pulsed gradient NMR.
AB  - We present a simple method by which the dimensions of shear-induced multilamellar
      vesicles (MLVs), also known as onions, can be measured during the shearing
      process itself. This approach is based on the use of a closely spaced train of
      magnetic field gradient pulses applied during a CPMG echo sequence. The CPMG
      train compensates flow effects while the frequency-dependence of apparent
      diffusion can reveal the onion size. We present here a simple phenomenological
      model for restricted diffusion in multilamellar vesicles, which may be used to
      interpret the resulting diffusion spectrum. We demonstrate this approach with
      MLVs formed from the lamellar phase of sodium dodecyl sulfate (SDS) in water and
      octanol.

PMID- 17533142
TI  - 4T split TEM volume head and knee coils for improved sensitivity and patient
      accessibility.
AB  - Split RF coils offer improved patient access by eliminating the need for the coil
      to be slid over the region of interest. For unshielded birdcage coils, the
      presence of end ring currents necessitates a direct electrical connection between
      two halves of the coil. For high-field (>3T) shielded birdcage coils, both the
      shield and the coil must be split and reliably connected electrically. This
      problem can be circumvented by the use of split TEM volume coils. Since the
      elements of a TEM coil are coupled inductively, no direct electrical connection
      between the halves is necessary. In this work we demonstrate that the effects of
      splitting the shield for head and knee TEMs can be compensated for, and
      performance retained. For the knee, the improved access allowed the coil diameter
      to be reduced, enhancing the sensitivity by 15-20%.

PMID- 17533143
TI  - Compensated adiabatic inversion pulses: broadband INEPT and HSQC.
AB  - When adiabatic fast passage is used to flip nuclear spins, sites with different
      chemical shifts are inverted at different times, causing refocusing errors. By
      mapping the phase evolution diagrams, we show that these effects can be
      accurately compensated with matched pairs of adiabatic pulses, either opposed or
      in the same sense, depending on the application. Applied to well-known
      heteronuclear polarization transfer experiments such as INEPT and HSQC, the
      requisite evolution of J-vectors is achieved irrespective of chemical shift or
      the duration of the adiabatic sweeps. By replacing conventional 180 degrees
      pulses, these new adiabatic sequences offer an order of magnitude improvement in
      effective bandwidth for the X-spins. Alternatively the experiments can be carried
      out with significantly reduced radiofrequency power. One- and two-dimensional
      spectra of (13)C in 13-cis-retinal at 600MHz have been used to demonstrate these
      advantages.

PMID- 17533144
TI  - Unusually mild phenotype of AADC deficiency in 2 siblings.
AB  - Aromatic L-amino acid decarboxylase deficiency is a rare neurotransmitter defect
      leading to serotonin, dopamine and norepinephrine deficiency. Affected
      individuals usually present in infancy with severe developmental delay,
      oculogyric crises and extrapyramidal movements. We present the clinical,
      molecular and biochemical features of a pair of siblings who presented with
      fatigability, hypersomnolence and dystonia and who showed excellent response to
      treatment. Analysis of CSF biogenic amines, plasma AADC levels and direct
      sequencing of the DDC gene was performed. CSF catecholamine metabolites were
      reduced, with elevation of 3-O-methyldopa. Plasma AADC activity was undetectable
      in both siblings, and decreased in their carrier parents. One missense mutation
      (853C>T) was found in exon 8, and a donor splice site mutation was found in the
      intron after exon 6 (IVS6+4A>T). Both siblings showed excellent response to MAO
      inhibitor and dopamine agonist treatment. This report expands the clinical
      spectrum of AADC deficiency and contributes to the knowledge of the genotype and
      phenotype correlation for the DDC gene. It is important to recognize the milder
      phenotypes of the disease as these patients might respond well to therapy.

PMID- 17533145
TI  - Differential sensitivity to interferon influences the replication and
      transcription of Urabe AM9 mumps virus variants in nerve cells.
AB  - Urabe AM9 mumps virus vaccine causes post-vaccination meningitis. Two variants of
      Urabe AM9 virus differ in their replication efficiency in human nerve cells, HN
      A(1081) variant being more neurotropic than HN-G(1081). The effect of interferon
      (IFN) on viral replication and transcription was analyzed. Priming of nerve cells
      with IFN reduced more significantly the replication of HN-G(1081) variant (from
      10(2.5) to 10(1.3) TCID(50)) than that of HN-A(1081) (from 10(3.5) to 10(2.6)
      TCID(50)). IFN-priming also reduced the transcription of HN-G(1081) genes, but
      not of HN-A(1081). The effect of viral infection on the transcription of cellular
      IFN responsive genes was analyzed. HN-A(1081) virus reduced the transcription of
      STAT1, STAT2, p48 and MxA in both unprimed and IFN-primed cells; whereas HN
      G(1081) virus just reduced MxA transcription. Since rubulavirus V protein
      inhibits IFN signaling, the V mRNA was cloned and sequenced, finding that HN
      G(1081) but not HN-A(1081) presented three extra G in the P/V edition site,
      producing the insertion of Gly156 in the V protein. Our results suggest that the
      replication efficiency of Urabe AM9 mumps virus variants is influenced by their
      sensitivity to interferon and their capacity to reduce the antiviral response.

PMID- 17533146
TI  - CXCL10/IP-10 release is induced by incubation of whole blood from tuberculosis
      patients with ESAT-6, CFP10 and TB7.7.
AB  - IFN-gamma responses to Mycobacterium tuberculosis specific antigens are used as
      in vitro diagnostic tests for tuberculosis infection. The tests are sensitive and
      specific for latent and active tuberculosis disease, but sensitivity may be
      reduced during immunosuppression. The objective of the study was to explore new
      ways to improve the diagnosis of tuberculosis infection using CXCL10 and IL-2 as
      alternative markers to IFN-gamma. CXCL10, IL-2, and IFN-gamma responses to
      stimulation with ESAT-6/CFP10/TB7.7 were assessed in 12 Quantiferon positive, 8
      Quantiferon negative tuberculosis patients and 11 Quantiferon negative controls.
      CXCL10 and IL-2 were determined by multiplex and IFN-gamma by the Quantiferon
      ELISA. The median antigen specific CXCL10, IFN-gamma, and IL-2 responses in
      patients with tuberculosis were 870 pg/ml (range 261-1576 pg/ml), 217 pg/ml (81
      1273 pg/ml), 59 pg/ml (14-276 pg/ml) respectively, and the CXCL10 responses were
      significantly higher than any of the other cytokines measured (p=0.001). In 4/7
      individuals with a negative (n=6) or indeterminate (n=1) Quantiferon test,
      antigen specific CXCL10 responses were detectable at high levels ranging from 196
      532 pg/ml. In conclusion CXCL10 was strongly induced after M. tuberculosis
      specific stimulation and sensitivity appeared superior to the Quantiferon test.
      Our findings suggest that CXCL10 may serve as an alternative or additional marker
      for the immunodiagnosis of tuberculosis.

PMID- 17533147
TI  - The chlamydial invasin-like protein gene conundrum.
AB  - Variants of an ilp (invasin-like protein) gene have been identified previously in
      Chlamydia caviae and in Chlamydia suis. The C. caviae ilp gene is interrupted by
      two frame shift mutations while the C. suis gene is intact. Characterization of
      the ilp gene in C. caviae passaged minimally in vitro showed that the two
      frameshift mutations were present in the original isolates. The gentamicin
      protection assay was used to determine if E. coli bacteria expressing the intact
      C. suis ilp could adhere to or invade HEp-2 cells. While inv+ clones showed
      increased adherence and invasion, no increase in adherence or invasion was
      observed for ilp+ clones. However, these clones were found to produce detectable
      amounts of ilp transcript. In a 48 h time course of C. suis culture, ilp
      transcript was initially detected at 8 h, peaked at 16 h, and declined
      subsequently. Antibodies specifically recognizing the putative functional domain
      of Ilp failed to detect any ilp-specific gene product in either E. coli or C.
      suis cultures. These data suggest that ilp does not encode a functional protein
      and raise questions about how ilp was introduced and maintained in Chlamydia.

PMID- 17533148
TI  - Characterization of PfDYN2, a dynamin-like protein of Plasmodium falciparum
      expressed in schizonts.
AB  - Dynamin superfamily members are large GTPases conserved through evolution mainly
      described as mechanochemical enzymes involved in membrane scission events. The
      Plasmodium falciparum dynamin-2 (Pfdyn2) gene was cloned from the FcB1 strain.
      PfDYN2 belongs to the dynamin-like protein subgroup of the dynamin superfamily
      since it possesses a large GTPase domain together with the conserved dynamin_M
      and GED domains. Recombinant PfDYN2 was able to bind GTP, to hydrolyze GTP into
      GDP and to self-associate in low-salt conditions. PfDYN2 expression was
      restricted to schizonts where it localized in punctuate structures within the
      parasite cytoplasm. PfDYN2 partly co-localized with markers of the parasite
      endoplasmic reticulum, Golgi apparatus and apicoplast, suggesting it could be
      implicated in vesicular trafficking and/or organelle fission events known to
      occur during the last hours of the parasite development in erythrocytes. PfDYN2
      and the previously described PfDYN1 are the only two dynamin superfamily members
      identified in the P. falciparum genome and the available data suggest that this
      situation is conserved in the Apicomplexa phylum.

PMID- 17533149
TI  - Lipooligosaccharide from Bordetella pertussis induces mature human monocyte
      derived dendritic cells and drives a Th2 biased response.
AB  - Bordetella pertussis has a distinctive cell wall lipooligosaccharide (LOS) that
      is released from the bacterium during bacterial division and killing. LOS
      directly participates in host-bacterial interactions, in particular influencing
      the dendritic cells' (DC) immune regulatory ability. We analyze LOS mediated toll
      like receptor (TLR) activation and dissect the role played by LOS on human
      monocyte-derived (MD)DC functions and polarization of the host T cell response.
      LOS activates TLR4-dependent signaling and induces mature MDDC able to secrete IL
      10. LOS-matured MDDC enhance allogeneic presentation and skew T helper (Th) cell
      polarization towards a Th2 phenotype. LOS protects MDDC from undergoing
      apoptosis, prolonging their longevity and their functions. Compared to
      Escherichia coli lipopolysaccharide (LPS), the classical DC maturation stimulus,
      LOS was a less efficient inducer of TLR4 signaling, MDDC maturation, IL-10
      secretion and allogeneic T cell proliferation and it was not able to induce IL
      12p70 production in MDDC. However, the MDDC apoptosis protection exerted by LOS
      and LPS were comparable. In conclusion, LOS treated MDDC are able to perform
      antigen presentation in a context that promotes licensing of Th2 effectors.
      Considering these properties, the use of LOS in the formulation of acellular
      pertussis vaccines to potentiate protective and adjuvant capacity should be taken
      into consideration.

PMID- 17533150
TI  - In-Cell Western analysis of Helicobacter pylori-induced phosphorylation of
      extracellular-signal related kinase via the transactivation of the epidermal
      growth factor receptor.
AB  - Helicobacter pylori activates extracellular-signal related (ERK) kinases in
      gastric epithelial cells, via transactivation of the EGF receptor (EGFR). H.
      pylori activation of EGFR may be relevant to epithelial hyperproliferation and
      gastric carcinogenesis. The aim of this study was to develop an 'In-Cell Western'
      (ICW) assay for quantitative examination of H. pylori-induced epithelial
      signalling, to enable the role of the EGFR in H. pylori-induced phosphorylation
      of ERK in epithelial cells to be ascertained. H. pylori strains were co-incubated
      with A431 and AGS cells. pERK and total ERK were quantified in situ using ICW
      analysis. H. pylori strains both with, and without a cag PAI, and Helicobacter
      felis, significantly increased pERK levels in A431 cells. The EGFR inhibitor EKB
      569 dose-dependently reduced H. pylori-induced ERK phosphorylation in A431 and
      AGS cells. A significantly lower reduction was observed with cag+ strains in A431
      but not AGS cells. The cag PAI was not necessary for EGFR signal transactivation.
      These data suggest that H. pylori induces pERK in epithelial cells partly via the
      EGFR pathway. Additional signalling mechanisms are likely to be involved in H.
      pylori-induced ERK phosphorylation. ICW analysis is a rapid quantitative method
      for evaluating the effects of inhibitors on H. pylori-induced cell signalling
      pathways of relevance to gastric carcinogenesis.

PMID- 17533151
TI  - Treponema denticola induces interleukin-8 and macrophage chemoattractant protein
      1 production in human umbilical vein epithelial cells.
AB  - Treponema denticola, a major pathogen of periodontitis, has also been detected in
      the lesions of atherosclerosis. The aim of this study was to investigate
      induction of chemokine production in human umbilical vein endothelial cells
      (HUVECs) by T. denticola and determine whether those chemokines were degraded by
      a protease, dentilisin. T. denticola ATCC35405 or dentilisin-deficient mutant K1
      were added to HUVECs and levels of interleukin-8 (IL-8) and monocyte
      chemoattractant protein-1 (MCP-1) in the culture supernatants were determined by
      enzyme-linked immunosorbent assay. T. denticola ATCC35405 induced production of
      IL-8 in a time-dependent manner, with both production of IL-8 and expression of
      IL-8 mRNA showing higher levels than with exposure to dentilisin-deficient mutant
      K1. Although exposure to ATCC35405 induced expression of MCP-1 mRNA in the
      HUVECs, MCP-1 levels were remained similar to that in unstimulated cells. IL-8
      and MCP-1 showed partial hydrolysis with exposure to T. denticola ATCC35405, but
      not with T. denticola K1. These results suggest that T. denticola can evade host
      defense mechanisms by modulating production of IL-8 and MCP-1, and that this play
      a role in the development of chronic infections such as periodontitis. The
      association of T. denticola infection to atherosclerosis was also discussed based
      on the present study.

PMID- 17533152
TI  - CD38 plays a role in effective containment of mycobacteria within granulomata and
      polarization of Th1 immune responses against Mycobacterium avium.
AB  - CD38 is a multifunctional ectoenzyme that behaves either as an enzyme, a cell
      adhesion molecule or as a cell surface receptor involved in cell signalling. It
      is expressed in cells of several lineages, including B and T lymphocytes, and
      macrophages. CD38 was shown to be important for the development of T-cell
      dependent humoral immune responses against extracellular pathogens. It also
      appears to be functionally important in macrophages, which are the host cells of
      Mycobacterium avium, an intracellular parasite that survives within these cells
      by avoiding a number of their microbicidal strategies. The present work aimed at
      investigating whether CD38 had any role on the immune response against
      mycobacterial infection. After intraperitoneal M. avium infection, the immune
      response of CD38KO mice was compared to that of their parental strain, C57Bl.6
      mice. Absence of CD38 rendered mice more susceptible to mycobacterial infection.
      This susceptibility seems to be due to ineffective Th1 differentiation and
      polarization, which is essential for the control of M. avium infection. In
      addition, absence of CD38 seems to compromise the maintenance of the
      granulomatous barrier, leading to dissemination and unrestrained growth of
      mycobacteria.

PMID- 17533153
TI  - The Paragon Algorithm, a next generation search engine that uses sequence
      temperature values and feature probabilities to identify peptides from tandem
      mass spectra.
AB  - The Paragon Algorithm, a novel database search engine for the identification of
      peptides from tandem mass spectrometry data, is presented. Sequence Temperature
      Values are computed using a sequence tag algorithm, allowing the degree of
      implication by an MS/MS spectrum of each region of a database to be determined on
      a continuum. Counter to conventional approaches, features such as modifications,
      substitutions, and cleavage events are modeled with probabilities rather than by
      discrete user-controlled settings to consider or not consider a feature. The use
      of feature probabilities in conjunction with Sequence Temperature Values allows
      for a very large increase in the effective search space with only a very small
      increase in the actual number of hypotheses that must be scored. The algorithm
      has a new kind of user interface that removes the user expertise requirement,
      presenting control settings in the language of the laboratory that are translated
      to optimal algorithmic settings. To validate this new algorithm, a comparison
      with Mascot is presented for a series of analogous searches to explore the
      relative impact of increasing search space probed with Mascot by relaxing the
      tryptic digestion conformance requirements from trypsin to semitrypsin to no
      enzyme and with the Paragon Algorithm using its Rapid mode and Thorough mode with
      and without tryptic specificity. Although they performed similarly for small
      search space, dramatic differences were observed in large search space. With the
      Paragon Algorithm, hundreds of biological and artifact modifications, all
      possible substitutions, and all levels of conformance to the expected digestion
      pattern can be searched in a single search step, yet the typical cost in search
      time is only 2-5 times that of conventional small search space. Despite this
      large increase in effective search space, there is no drastic loss of
      discrimination that typically accompanies the exploration of large search space.

PMID- 17533154
TI  - Galpha12/13-mediated up-regulation of TRPC6 negatively regulates endothelin-1
      induced cardiac myofibroblast formation and collagen synthesis through nuclear
      factor of activated T cells activation.
AB  - Sustained elevation of [Ca(2+)](i) has been implicated in many cellular events.
      We previously reported that alpha subunits of G(12) family G proteins
      (Galpha(12/13)) participate in sustained Ca(2+) influx required for the
      activation of nuclear factor of activated T cells (NFAT), a Ca(2+)-responsive
      transcriptional factor, in rat neonatal cardiac fibroblasts. Here, we demonstrate
      that Galpha(12/13)-mediated up-regulation of canonical transient receptor
      potential 6 (TRPC6) channels participates in sustained Ca(2+) influx and NFAT
      activation by endothelin (ET)-1 treatment. Expression of constitutively active
      Galpha(12) or Galpha(13) increased the expression of TRPC6 proteins and basal
      Ca(2+) influx activity. The treatment with ET-1 increased TRPC6 protein levels
      through Galpha(12/13), reactive oxygen species, and c-Jun N-terminal kinase (JNK)
      dependent pathways. NFAT is activated by sustained increase in [Ca(2+)](i)
      through up-regulated TRPC6. A Galpha(12/13)-inhibitory polypeptide derived from
      the regulator of the G-protein signaling domain of p115-Rho guanine nucleotide
      exchange factor and a JNK inhibitor, SP600125, suppressed the ET-1-induced
      increase in expression of marker proteins of myofibroblast formation through a
      Galpha(12/13)-reactive oxygen species-JNK pathway. The ET-1-induced myofibroblast
      formation was suppressed by overexpression of TRPC6 and CA NFAT, whereas it was
      enhanced by TRPC6 small interfering RNAs and cyclosporine A. These results
      suggest two opposite roles of Galpha(12/13) in cardiac fibroblasts. First,
      Galpha(12/13) mediate ET-1-induced myofibroblast formation. Second, Galpha(12/13)
      mediate TRPC6 up-regulation and NFAT activation that negatively regulates ET-1
      induced myofibroblast formation. Furthermore, TRPC6 mediates hypertrophic
      responses in cardiac myocytes but suppresses fibrotic responses in cardiac
      fibroblasts. Thus, TRPC6 mediates opposite responses in cardiac myocytes and
      fibroblasts.

PMID- 17533155
TI  - Properties of actin from the fission yeast Schizosaccharomyces pombe and
      interaction with fission yeast profilin.
AB  - The fission yeast Schizosaccharomyces pombe serves as a model system for studying
      role of actin cytoskeleton, since it has simple actin cytoskeletons and is
      genetically tractable. In contrast, biochemical approaches using this organism
      are still developing; fission yeast actin has so far not been isolated in its
      native form and characterized, and therefore, biochemical assays of fission yeast
      actin-binding proteins (ABPs) or myosin have been performed using rabbit skeletal
      muscle actin that may interact with the fission yeast ABPs in a manner different
      from fission yeast actin. Here, we report a novel method for isolating
      functionally active actin from fission yeast cells. The highly purified fission
      yeast actin polymerized with kinetics somewhat different from those of muscle
      actin and forms filaments that are structurally indistinguishable from skeletal
      muscle actin filaments. The fission yeast actin was a significantly weaker
      activator of Mg(2+)-ATPase of HMM of skeletal muscle myosin than muscle actin.
      The fission yeast profilin Cdc3 suppressed polymerization of fission yeast actin
      more effectively than that of muscle actin and showed an affinity for fission
      yeast actin higher than for muscle actin. The establishment of purification of
      fission yeast actin will enable reconstruction of physiologically relevant
      interactions between the actin and fission yeast ABPs or myosins and contribute
      to clarification of function of actin cytoskeleton in various cellular
      activities.

PMID- 17533156
TI  - Current risk estimates based on the A-bomb survivors data - a discussion in terms
      of the ICRP recommendations on the neutron weighting factor.
AB  - Currently, most analyses of the A-bomb survivors' solid tumour and leukaemia data
      are based on a constant neutron relative biological effectiveness (RBE) value of
      10 that is applied to all survivors, independent of their distance to the
      hypocentre at the time of bombing. The results of these analyses are then used as
      a major basis for current risk estimates suggested by the International
      Commission on Radiological Protection (ICRP) for use in international safety
      guidelines. It is shown here that (i) a constant value of 10 is not consistent
      with weighting factors recommended by the ICRP for neutrons and (ii) it does not
      account for the hardening of the neutron spectra in Hiroshima and Nagasaki, which
      takes place with increasing distance from the hypocentres. The purpose of this
      paper is to present new RBE values for the neutrons, calculated as a function of
      distance from the hypocentres for both cities that are consistent with the ICRP60
      neutron weighting factor. If based on neutron spectra from the DS86 dosimetry
      system, these calculations suggest values of about 31 at 1000 m and 23 at 2000 m
      ground range in Hiroshima, while the corresponding values for Nagasaki are 24 and
      22. If the neutron weighting factor that is consistent with ICRP92 is used, the
      corresponding values are about 23 and 21 for Hiroshima and 21 and 20 for
      Nagasaki, respectively. It is concluded that the current risk estimates will be
      subject to some changes in view of the changed RBE values. This conclusion does
      not change significantly if the new doses from the Dosimetry System DS02 are
      used.

PMID- 17533157
TI  - Monte Carlo modeling for individual monitoring.
AB  - Thanks to the continuously increasing computer power, Monte Carlo techniques are
      progressively playing a key role in radiation dosimetry, in the field of dose
      assessment from internal and external exposures. Internal dosimetry aspects are
      presented in a separate paper in the same issue. For external exposure,
      individual monitoring techniques provide suitable tools to estimate the personal
      dose equivalent Hp(d), that should be a conservative estimate of the effective
      dose. Personal dosemeters should be designed and type tested in terms of Hp(d)
      and also irradiations facilities should be characterised in terms of the same
      operational quantity. This paper provides a concise overview on the role played
      by monte Carlo techniques in the field.

PMID- 17533158
TI  - The response of the BTI bubble detectors in mixed gamma-neutron workplace fields.
AB  - Bubble detectors have become a mature technology and are used as neutron
      dosemeters in a wide range of applications. At the SCK-CEN and Belgonucleaire
      they are used as official personal neutron dosemeter for the personnel. In the
      European Commission (EC) project of Evaluation of Individual Dosimetry in Mixed
      Neutron and Photon Radiation Fields (EVIDOS), a whole range of neutron dosemeters
      were irradiated in workplace fields in nuclear installations in Europe, including
      two types of bubble detectors. The responses of the bubble detectors are compared
      with the reference values determined using a directional spectrometer and a
      reference instrument to measure Hp(10).

PMID- 17533159
TI  - Use of statistical checks as maintenance tools for TLD readers.
AB  - Although the values of different parameters may remain within permissible limits
      during the operation of a thermoluminescent dosemeter (TLD) reader, certain
      effects can become apparent only when a long-term followup of these parameters is
      performed. In order to ensure an accurate and reliable operation of a TLD reader,
      the system characteristics must be monitored continuously. Long-term statistical
      checks of key system parameters may give a broader insight into the operational
      characteristics of the TLD reader and may help for proper maintenance of the
      system. The photomultipliers noise, the internal reference light source stability
      and the A to D reference voltage were found to be critical parameters, which have
      a major influence on the accuracy and stability of the system. A followup of
      these parameters for a period of about 10 y is presented, and some problems are
      seen to be reflected in the distributions.

PMID- 17533160
TI  - Dose trends in occupational radiation exposure in Europe results from the ESOREX
      project.
AB  - The ESOREX project was initiated in 1997 by the EC DG TREN and it was executed by
      the BfS/Germany in close co-operation with the State Office for Nuclear
      Safety/Czech Republic). It consists of surveys on radiation monitoring and
      exposure carried out in the 30 European states. The study provides comparable
      descriptions of the national administrative structures used to monitor and
      register individual occupational radiation exposure and the national dose
      statistics. The analysis of time series about the occupational radiation exposure
      in different work sectors allows the evaluation of changes and trends after the
      transposure of the Council Directive 96/29/EURATOM. From 1996 to 2000
      occupational radiation protection led partly to substantial dose reductions,
      primarily in the nuclear sector and in the sector of natural sources. General
      industry performs less successfully in the reduction of radiation exposure. Work
      sectors with traditionally low doses like the medical sector or research and
      education showed less of a reduction. Yet, the dose reductions in these sectors
      show that even at levels of low exposures there is still room for improvement and
      dose reduction.

PMID- 17533161
TI  - Quantitative analysis of the factors responsible for over or under dose of 131 I
      therapy patients of hyperthyroidism.
AB  - Radioiodine (131 I) therapy has been in use for more than 60 y. Several protocols
      have been suggested and used for prescribing the activity to be administered to
      the patients for the treatment of hyperthyroidism; application of these protocols
      may result in an under or over dose of the hyperthyroid patients. The main
      objective of this study was to carry out quantitative analysis of the factors
      responsible for possible under or over dosage of the patients. In this regard, a
      total of 59 patients [15 diffuse goitre (DG) and 44 nodular goitre (NG) cases]
      were studied. In order to compare the thyroid doses calculated by using different
      protocols, the dosimetric approach was followed. 131 I uptakes were measured
      after 24 and 48 h, respectively, by giving 0.5 MBq of 131 I to each patient.
      Thyroid mass and effective half-life were also calculated for each patient and
      the variations in the thyroid doses were analysed. According to the results 28
      and 54% patients were under dosed and 72 and 46% patients were over dosed with DG
      and NG, respectively. The protocols, which have not taken into account the
      thyroid mass, multi pre-therapeutic 131 I uptakes and the effective half-life of
      131 I of the individual patient, showed a higher degree of deviation from the
      required thyroid dose. Besides these parameters, some fundamental factors such as
      radiosensitivity, previous exposure to thyroid drugs and duration of the disease
      are recommended to be incorporated, which can certainly affect the clinical out
      comes.

PMID- 17533162
TI  - Biomarkers to disclose recent intake of alcohol: potential of 5-hydroxytryptophol
      glucuronide testing using new direct UPLC-tandem MS and ELISA methods.
AB  - AIMS: This study compared two new methods for direct determination of 5
      hydroxytryptophol glucuronide (GTOL) in urine, a biomarker for detection of
      recent alcohol consumption. METHODS: Urine samples were collected from ten
      alcoholic patients during recovery from intoxication. A direct injection ultra
      performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method
      for measurement of the urinary GTOL to 5-hydroxyindoleacetic acid (5-HIAA) ratio,
      and an ELISA assay for direct measurement of GTOL, were used. Comparison was made
      with the urinary ethanol and ethyl glucuronide (EtG) concentrations. RESULTS: The
      breath ethanol concentration on admission ranged between 1.0-3.1 g/l. The UPLC
      MS/MS method showed a median detection time of 39 h for an elevated urinary
      GTOL/5-HIAA ratio, while EtG was detected for a median of 65 h. Determination of
      GTOL by the ELISA assay showed 87% sensitivity in detecting positive samples at a
      44% specificity, as compared with the UPLC-MS/MS method. CONCLUSIONS: The lower
      sensitivity of the urinary GTOL/5-HIAA ratio compared with EtG for recent
      drinking may be clinically useful, in cases where the EtG test provides an
      unwanted high sensitivity for intake of only small amounts of alcohol or
      unintentional ethanol exposure.

PMID- 17533163
TI  - Ca2+-activated K+ channels involved in duodenal dismotility induced by ethanol.
AB  - The purpose of this study was to investigate the role of K+ channels in duodenal
      dismotility induced by ethanol in vitro. The amplitude of spontaneous
      contractions was reduced by ethanol in longitudinal and circular muscle, while
      frequency did not change. Charybdotoxin antagonized ethanol-induced inhibition of
      the amplitude of spontaneous contractions. Ethanol decreased ACh-induced
      contractions and this effect was cancelled out by charybdotoxin. Ca2+-activated
      K+ channels may be involved in duodenal dismotility induced by ethanol.

PMID- 17533164
TI  - Alcohol abuse among U.S. Navy recruits who were maltreated in childhood.
AB  - AIMS: To examine relationships between childhood maltreatment and alcohol-related
      problems among U.S. Navy recruits. METHODS: An anonymous sample of 5697 Navy
      recruits completed a survey regarding their alcohol consumption, alcohol problems
      (binge drinking, drinking until drunk, alcohol dependence, alcohol-related
      arrests), and experiences of childhood physical and sexual abuse. RESULTS: Most
      of the recruits used alcohol, and a substantial proportion reported histories of
      childhood maltreatment. Recruits who had been victimized as children were more
      likely to use alcohol. Furthermore, among drinkers, those who had been abused
      were more likely to exhibit alcohol problems than were non-abused drinkers.
      CONCLUSION: Substantial numbers of personnel with alcohol-related problems may be
      using alcohol to self-medicate due to a history of childhood abuse. Attention to
      the association between alcohol abuse and childhood maltreatment might help
      improve the efficacy of military alcohol reduction programs.

PMID- 17533165
TI  - Commentary: Dietary patterns in transition can inform health risk, but detailed
      assessments are needed to guide recommendations.

PMID- 17533166
TI  - Prevalence of resistance to nevirapine in mothers and children after single-dose
      exposure to prevent vertical transmission of HIV-1: a meta-analysis.
AB  - BACKGROUND: Single-dose nevirapine (NVP) is the main option for the prevention of
      mother-to-child transmission (PMTCT) of HIV-1 in countries with limited
      resources. However, the use of single-dose NVP results in HIV-1 viral resistance
      which could compromise the success of subsequent treatment of mother and child
      with antiretroviral combinations that include non-nucleosidic-reverse
      transcriptase inhibitors. This systematic review and meta-analysis of summarized
      data aimed to estimate the proportion of mothers and children with NVP resistance
      mutations detected in plasma samples 4-8 weeks postpartum after single-dose NVP
      use for PMTCT. METHODS: Systematic search of electronic databases (MEDLINE,
      PASCAL) and conference proceedings (1997 to February 2006). Inclusion of all
      studies, without design, place or language restrictions, meeting the following
      criteria: use of single-dose NVP; viral genotyping performed with standard
      sequence analyses, between 4 and 8 weeks postpartum, in plasma samples; available
      public report; report of mothers' median baseline plasma HIV-1 RNA levels. Data
      extraction by two independent reviewers using a standardized form created for
      this purpose. Logistic random effect models to obtain pooled estimates.
      Univariable and multivariable meta-regression to explore sources of
      heterogeneity. RESULTS: The pooled estimate of NVP resistance prevalence was
      35.7% [95% confidence interval (CI) 23.0-50.6] in women in 10 study arms using
      single-dose NVP +/- other antepartum antiretrovirals and 4.5% (CI 2.1-9.4) in
      three study arms providing also postpartum antiretrovirals (adjusted odds ratio
      0.08; CI 0.04-0.16). The corresponding estimates in children were 52.6% (CI 37.7
      67.0) in seven study arms using single-dose NVP only and 16.5% (CI 8.9-28.3) in
      eight study arms combining single-dose NVP with other antiretrovirals.
      CONCLUSIONS: Single-dose NVP is widely used for PMTCT in resource-poor settings,
      but the burden of viral resistance is high in both women and children. It is
      substantially lower in studies providing additional postpartum antiretrovirals.
      The clinical implications of these findings should be further investigated.

PMID- 17533167
TI  - Whole brain functional connectivity in the early blind.
AB  - Early visual deprivation can lead to changes in the brain, which may be explained
      by either of two hypotheses. The general loss hypothesis has been proposed to
      explain maladjustments, while the compensatory plasticity hypothesis may explain
      a superior ability in the use of the remaining senses. Most previous task-based
      functional MRI (fMRI) studies have supported the compensatory plasticity
      hypothesis, but it has been difficult to provide evidence to support the general
      loss hypothesis, since the blind cannot execute visual tasks. The study of
      resting state fMRI data may provide an opportunity to simultaneously detect the
      two aspects of changes in the blind. In this study, using a whole brain
      perspective, we investigated the decreased and increased functional
      connectivities in the early blind using resting state fMRI data. The altered
      functional connectivities were identified by comparing the correlation
      coefficients of each pair of brain regions of 16 early blind subjects (9 males;
      age range: 15.6-29.3 years, mean age: 22.1 years) with the corresponding
      coefficients of gender- and age-matched sighted volunteers. Compared with the
      sighted subjects, the blind demonstrated the decreased functional connectivities
      within the occipital visual cortices as well as between the occipital visual
      cortices and the parietal somatosensory, frontal motor and temporal multisensory
      cortices. Such differences may support the general loss hypothesis. However, we
      also found that the introduction of Braille earlier in life and for longer daily
      practice times produced stronger functional connectivities between these brain
      areas. These findings may support the compensatory plasticity hypothesis.
      Additionally, we found several increased functional connectivities between the
      occipital cortices and frontal language cortices in those with early onset of
      blindness, which indicate the predominance of compensatory plasticity. Our
      findings indicate that changes in the functional connectivities in the resting
      state may be an integrated reflection of general loss and compensatory plasticity
      when a single sensory modality is deprived.

PMID- 17533168
TI  - Angiogenesis is associated with blood-brain barrier permeability in temporal lobe
      epilepsy.
AB  - Previous studies from our group, focusing on neuro-glial remodelling in human
      temporal lobe epilepsy (TLE), have shown the presence of immature vascular cells
      in various areas of the hippocampus. Here, we investigated angiogenic processes
      in hippocampi surgically removed from adult patients suffering from chronic
      intractable TLE, with various aetiologies. We compared hippocampi from TLE
      patients to hippocampi obtained after surgery or autopsy from non-epileptic
      patients (NE). We quantified the vascular density, checked for the expression of
      angiogenic factors and their receptors and looked for any blood-brain barrier
      (BBB) leakage. We used a relevant model of rat limbic epilepsy, induced by
      lithium-pilocarpine treatment, to understand the sequence of events. In humans,
      the vessel density was significantly higher in TLE than in NE patients. This was
      neither dependent on the aetiology nor on the degree of neuronal loss, but was
      positively correlated with seizure frequency. In the whole hippocampus, we
      observed many complex, tortuous microvessels. In the dentate gyrus, when the
      granular layer was dispersed, long microvessels appeared radially orientated.
      Vascular endothelial factor (VEGF) and tyrosine kinase receptors were detected in
      different types of cells. An impairment of the BBB was demonstrated by the loss
      of tight junctions and by Immunoglobulines G (IgG) leakage and accumulation in
      neurons. In the rat model of TLE, VEGF over-expression and BBB impairment
      occurred early after status epilepticus, followed by a progressive increase in
      vascularization. In humans and rodents, angiogenic processes and BBB disruption
      were still obvious in the chronic focus, probably activated by recurrent
      seizures. We suggest that the persistent leakage of serum IgG in the interstitial
      space and their uptake by neurons may participate in hypoperfusion and in
      neuronal dysfunction occurring in TLE.

PMID- 17533170
TI  - Anosognosia for hemiplegia after stroke is a multifaceted phenomenon: a
      systematic review of the literature.
AB  - Anosognosia is the lack of awareness or the underestimation of a specific deficit
      in sensory, perceptual, motor, affective or cognitive functioning due to a brain
      lesion. This self-awareness deficit has been studied mainly in stroke hemiplegic
      patients, who may report no deficit, overestimate their abilities or deny that
      they are unable to move a paretic limb. In this review, a detailed search of the
      literature was conducted to illustrate clinical manifestations, pathogenetic
      models, diagnostic procedures and unresolved issues in anosognosia for motor
      impairment after stroke. English and French language papers spanning the period
      January 1990-January 2007 were selected using PubMed Services and utilizing
      research words stroke, anosognosia, awareness, denial, unawareness, hemiplegia.
      Papers reporting sign-based definitions, neurological and neuropsychological data
      and the results of clinical trials or historical trends in diagnosis were chosen.
      As a result, a very complex and multifaceted phenomenon emerges, whose variable
      behavioural manifestations often produce uncertainties in conceptual definitions
      and diagnostic procedures. Although a number of questionnaires and diagnostic
      methods have been developed to assess anosognosia following stroke in the last 30
      years, they are often limited by insufficient discriminative power or a narrow
      focus on specific deficits. As a consequence, epidemiological estimates are
      variable and incidence rates have ranged from 7 to 77% in stroke. In addition,
      the pathogenesis of anosognosia is widely debated. The most recent
      neuropsychological models have suggested a defect in the feedforward system,
      while neuro-anatomical studies have consistently reported on the involvement of
      the right cerebral hemisphere, particularly the prefrontal and parieto-temporal
      cortex, as well as insula and thalamus. We highlight the need for a
      multidimensional assessment procedure and suggest some potentially productive
      directions for future research about unawareness of illness.

PMID- 17533169
TI  - 3D maps from multiple MRI illustrate changing atrophy patterns as subjects
      progress from mild cognitive impairment to Alzheimer's disease.
AB  - Mild cognitive impairment (MCI), particularly the amnestic subtype (aMCI), is
      considered as a transitional stage between normal aging and a diagnosis of
      clinically probable Alzheimer's disease (AD). The aMCI construct is particularly
      useful as it provides an opportunity to assess a clinical stage which in most
      subjects represents prodromal AD. The aim of this study was to assess the
      progression of cerebral atrophy over multiple serial MRI during the period from
      aMCI to progression to AD. Thirty-three subjects were selected that fulfilled
      clinical criteria for aMCI and had three serial MRI scans: the first scan
      approximately 3 years before the diagnosis of AD, the second scan approximately 1
      year before, and the third scan at the time of the diagnosis of AD. A group of 33
      healthy controls were age and gender-matched to the study cohort. Voxel-based
      morphometry (VBM) was used to assess patterns of grey matter atrophy in the aMCI
      subjects at each time-point compared to the control group. Customized templates
      and prior probability maps were used to avoid normalization and segmentation
      bias. The pattern of grey matter loss in the aMCI subject scans that were 3 years
      before the diagnosis of AD was focused primarily on the medial temporal lobes,
      including the amygdala, anterior hippocampus and entorhinal cortex, with some
      additional involvement of the fusiform gyrus, compared to controls. The extent
      and magnitude of the cerebral atrophy further progressed by the time the subjects
      were 1 year before the diagnosis of AD. At this point atrophy in the temporal
      lobes spread to include the middle temporal gyrus, and extended into more
      posterior regions of the temporal lobe to include the entire extent of the
      hippocampus. The parietal lobe also started to become involved. By the time the
      subjects had progressed to a clinical diagnosis of AD the pattern of grey matter
      atrophy had become still more widespread with more severe involvement of the
      medial temporal lobes and the temporoparietal association cortices and, for the
      first time, substantial involvement of the frontal lobes. This pattern of
      progression fits well with the Braak and Braak neurofibrillary pathological
      staging scheme in AD. It suggests that the earliest changes occur in the anterior
      medial temporal lobe and fusiform gyrus, and that these changes occur at least 3
      years before progression to the diagnosis of AD. These results also suggest that
      3D patterns of grey matter atrophy may help to predict the time to the first
      diagnosis of AD in subjects with aMCI.

PMID- 17533171
TI  - The putative tumor suppressor Tsc-22 is downregulated early in chemically induced
      hepatocarcinogenesis and may be a suppressor of Gadd45b.
AB  - Tsc-22 is a novel tumor suppressor gene that represents a new class of
      transcription factors that has transcriptional repressor activity. We found Tsc
      22 downregulation in livers from B6C3F1 mice following treatment for 2 weeks with
      carcinogenic doses of the antianxiety drug oxazepam (2500 ppm) or the peroxisome
      proliferator Wyeth-14,643 (500 ppm) but not with two other carcinogens such as o
      nitrotoluene or methyleugenol or three noncarcinogens including p-nitrotoluene,
      eugenol, or acetaminophen. The expression of Tsc-22 was also repressed in B6C3F1
      mouse liver tumors that were induced by several chemicals from 2-year
      carcinogenicity studies as well as in spontaneous liver tumors. To identify
      potential Tsc-22 target genes in mouse liver, we transfected small interference
      RNA (SiRNA) designed to inhibit Tsc-22 into murine liver BNL-CL.2 cells. We
      selected two potential transcriptional targets of Tsc-22, growth arrest and DNA
      damage-inducible gene 45 beta (Gadd45b) and leucine zipper, putative tumor
      suppressor 2 (Lzts2) to test based on our previous complementary DNA microarray
      studies, showing that expression of these cancer-associated genes was increased
      when Tsc-22 was repressed. SiRNA treatment of BNL-CL.2 cells with Tsc-22
      oligonucleotides but not nonspecific oligonucleotides decreased RNA and protein
      expression of Tsc-22 by 80-90%, while expression of Gadd45b gene, but not Lzts2,
      was increased over time after an initial decrease. Treatment of these cells with
      oxazepam for 48 h also resulted in decreased Tsc-22 and increased Gadd45b
      expression. These data provide evidence that Tsc-22 is a suppressor of Gadd45b
      expression, which may contribute to an early antiapoptotic response.

PMID- 17533172
TI  - The built environment and obesity.
AB  - Obesity results from a complex interaction between diet, physical activity, and
      the environment. The built environment encompasses a range of physical and social
      elements that make up the structure of a community and may influence obesity.
      This review summarizes existing empirical research relating the built environment
      to obesity. The Medline, PsychInfo, and Web of Science databases were searched
      using the keywords "obesity" or "overweight" and "neighborhood" or "built
      environment" or "environment." The search was restricted to English-language
      articles conducted in human populations between 1966 and 2007. To meet inclusion
      criteria, articles had to 1) have a direct measure of body weight and 2) have an
      objective measure of the built environment. A total of 1,506 abstracts were
      obtained, and 20 articles met the inclusion criteria. Most articles (84%)
      reported a statistically significant positive association between some aspect of
      the built environment and obesity. Several methodological issues were of concern,
      including the inconsistency of measurements of the built environment across
      studies, the cross-sectional design of most investigations, and the focus on
      aspects of either diet or physical activity but not both. Given the importance of
      the physical and social contexts of individual behavior and the limited success
      of individual-based interventions in long-term obesity prevention, more research
      on the impact of the built environment on obesity is needed.

PMID- 17533173
TI  - Cochlear implants: the young people's perspective.
AB  - Cochlear implantation is a relatively new procedure, which has already had
      significant impact on the lives of many profoundly deaf children and adults, in
      providing useful hearing to those unable to benefit significantly from hearing
      aids. After 16 years of cochlear implantation in the United Kingdom, there is now
      a body of evidence covering a range of outcomes, much of which covers perceptual
      and linguistic outcomes. This study looks at the impact of cochlear implantation
      on a group of 29 young people aged 13-16 years, using a semistructured
      questionnaire. It examines issues from the perspective of the young people
      themselves, including their understanding of and degree of satisfaction with the
      way their implant works for them, their social and communication abilities and
      choices, their educational challenges, and their identity. It concludes that the
      young people in this group feel positive toward their cochlear implants and the
      decisions made on their behalf by parents. Many have a flexible attitude to
      communication modes and an identity which is not fixed in terms of conventional
      descriptors.

PMID- 17533174
TI  - Variation in mutation rate and polymorphism among mitochondrial genes of Silene
      vulgaris.
AB  - The prevailing wisdom of the plant mitochondrial genome is that it has very low
      substitution rates, thus it is generally assumed that nucleotide diversity within
      species will also be low. However, recent evidence suggests plant mitochondrial
      genes may harbor variable and sometimes high levels of within-species
      polymorphism, a result attributed to variance in the influence of selection.
      However, insufficient attention has been paid to the effect of among-gene
      variation in mutation rate on varying levels of polymorphism across loci. We
      measured levels of polymorphism in seven mitochondrial gene regions across a
      geographically wide sample of the plant Silene vulgaris to investigate whether
      individual mitochondrial genes accumulate polymorphisms equally. We found that
      genes vary significantly in polymorphism. Tests based on coalescence theory show
      that the genes vary significantly in their scaled mutation rate, which, in the
      absence of differences among genes in effective population size, suggests these
      genes vary in their underlying mutation rate. Further evidence that among-gene
      variance in polymorphism is due to variation in the underlying mutation rate
      comes from a significant positive relationship between the number of segregating
      sites and silent site divergence from an outgroup. Contrary to recent studies, we
      found unconvincing evidence of recombination in the mitochondrial genome, and
      generally confirm the standard model of plant mitochondria characterized by low
      substitution rates and no recombination. We also show no evidence of significant
      variation in the strength or direction of selection among genes; this result may
      be expected if there is no recombination. The present study provides some of the
      most thorough data on plant mitochondrial polymorphism, and provides compelling
      evidence for mutation rate variation among genes. The study also demonstrates the
      difficulty in establishing a null model of mitochondrial genome polymorphism, and
      thus the difficulty, in the absence of a comparative approach, in testing the
      assumption that low substitution rates in plant mitochondria lead to low
      polymorphism.

PMID- 17533175
TI  - Integrating quantitative information from ChIP-chip experiments into motif
      finding.
AB  - Identifying binding locations of transcription factors (TFs) within long segments
      of noncoding DNA is a challenging task. Recent chromatin immunoprecipitation on
      microarray (ChIP-chip) experiments utilizing tiling arrays are especially
      promising for this task since they provide high-resolution genome-wide maps of
      the interactions between the TFs and the DNA. Data from these experiments are
      invaluable for characterizing DNA recognition profiles (regulatory motifs) of
      TFs. A 2-step paradigm is commonly used for performing motif searches based on
      ChIP-chip data. First, candidate bound sequences that are in the order of 500
      1000 bp are identified from ChIP-chip data. Then, motif searches are performed
      among these sequences. These 2 steps are typically carried out in a disconnected
      fashion in the sense that the quantitative nature of the ChIP-chip information is
      ignored in the second step. More specifically, all bound regions are assumed to
      equally likely have the motif(s), and the motifs are assumed to reside at any
      position of the bound regions with equal probability. We develop a conditional
      two-component mixture (CTCM) model that relaxes both these common assumptions by
      adaptively incorporating ChIP-chip information. The performances of the new and
      existing methods are compared using simulated data and ChIP-chip data from
      recently available ENCODE studies (Consortium, 2004). These studies indicate that
      CTCM efficiently utilizes the information available in the ChIP-chip experiments
      and has superior sensitivity and specificity especially when the motif of
      interest has low abundance among the ChIP-chip bound regions and/or low
      information content.

PMID- 17533176
TI  - One-year follow-up of very preterm infants who received lucinactant for
      prevention of respiratory distress syndrome: results from 2 multicenter
      randomized, controlled trials.
AB  - BACKGROUND: The benefits of exogenous surfactants for prevention or treatment of
      respiratory distress syndrome are well established, but there is a paucity of
      long-term follow-up data from surfactant-comparison trials. OBJECTIVE: We sought
      to determine and compare survival and pulmonary and neurodevelopmental outcomes
      through 1 year corrected age of preterm infants who received lucinactant and
      other surfactants in the SELECT (Safety and Effectiveness of Lucinactant Versus
      Exosurf in a Clinical Trial) and STAR (Surfaxin Therapy Against Respiratory
      Distress Syndrome) trials individually and, secondarily, from analysis using
      combined data from these 2 trials. METHODS: All infants from both trials who were
      randomly assigned to administration of lucinactant (175 mg/kg), colfosceril
      palmitate (67.5 mg/kg), beractant (100 mg/kg), or poractant alfa (175 mg/kg) were
      prospectively followed through 1 year corrected age, at which point masked
      assessment of outcomes was performed for surviving infants. One-year survival was
      a key outcome of interest. Other parameters assessed included rates of
      rehospitalization and respiratory morbidity and gross neurologic status. Data
      were analyzed by comparing the different surfactants within each trial and, in
      secondary analysis, combining data from both trials to compare lucinactant versus
      the animal-derived surfactants (beractant and poractant) used in these trials.
      Survival rates over time were compared by using the Wilcoxon test for survival
      through 1 year corrected age and logistic regression for comparison of fixed time
      points. The latter analyses were performed by using the prespecified approach,
      where loss to follow-up or withdrawal of consent was imputed as a death, and also
      using raw data. Other outcomes were analyzed by using the Cochran-Mantel-Haenszel
      test or logistic regression for categorical data, and analysis of variance on
      ranks was used for continuous data. RESULTS: Very few cases were lost to follow
      up in either trial (29 of 1546 enrolled in both trials [1.9%]). In the primary
      analysis of the SELECT trial comparing lucinactant to either colfosceril or
      beractant, there were no significant differences in the proportion of infants who
      were alive through 1 year corrected age. Fixed-time-point estimates of mortality
      at 1 year corrected age imputing loss to follow-up as a death were 28.1% for
      lucinactant, 31.0% for colfosceril, and 31.0% for beractant. By using raw data
      without imputing loss to follow-up as a death, mortality estimates at 1 year
      corrected age were computed to be 26.6%, 29.1%, and 28.3%, respectively. In the
      primary analysis of the STAR trial, significantly more infants treated with
      lucinactant were alive through 1 year corrected age compared with those who
      received poractant alfa. Fixed time estimates of mortality at 1 year corrected
      age imputing loss to follow-up as a death were 19.4% for lucinactant and 24.2%
      for poractant. These estimates using raw data that did not impute loss to follow
      up as a death were 18.6% and 21.9%, respectively. In the combined analysis,
      survival through 1 year corrected age was higher for infants in the lucinactant
      group versus that of the infants in the animal-derived surfactants (beractant and
      poractant) group. The fixed-time-point estimates of mortality at 1 year corrected
      age imputing loss to follow-up as a death for lucinactant and animal-derived
      surfactants were 26.0% and 29.4%, respectively. However, the 1-year-corrected-age
      estimates using combined raw data were 24.6% for the lucinactant group and 26.7%
      for the animal-derived surfactant group. The incidence of postdischarge
      rehospitalizations, total number of rehospitalizations, incidence of respiratory
      illnesses, and total number of respiratory illnesses were generally similar among
      those in the treatment groups. Neurologic status at 1 year corrected age was
      essentially similar between infants who received lucinactant and those who
      received all other surfactants used in these 2 trials. CONCLUSIONS: Findings from
      this 1-year follow-up of both lucinactant trials indicate that this new peptide
      based synthetic surfactant is at least as good, if not superior, to animal
      derived surfactants for prevention of respiratory distress syndrome and may be a
      viable alternative to animal-derived products.

PMID- 17533178
TI  - The role of mometasone furoate aqueous nasal spray in the treatment of adenoidal
      hypertrophy in the pediatric age group: preliminary results of a prospective,
      randomized study.
AB  - OBJECTIVE: We evaluated the efficacy of mometasone furoate aqueous nasal spray in
      decreasing adenoid size and reducing the severity of chronic nasal obstruction
      symptoms in children affected by adenoidal hypertrophy. METHODS: Sixty children
      were recruited in a 2-stage, randomized, placebo-controlled trial. All patients
      complained of chronic nasal obstruction symptoms, and nasal endoscopy showed >75%
      choanal obstruction attributable to adenoid pads. In the first stage, 30 patients
      (group A) underwent mometasone treatment (50 microg per nostril per day) for 40
      days, and 30 children (group B) received placebo. In the second stage, at the end
      of the first 40-day treatment period, patients in group A who showed subjective
      and objective clinical improvement were divided into 2 subgroups; group A1 (11
      children) received topical intranasal steroid treatment on alternate days for the
      first 2 weeks per month, whereas group A2 (10 children) continued daily
      mometasone treatment for the first 2 weeks per month. After 3 months, all
      children were reassessed. RESULTS: Fifty-seven children completed the study
      according to the protocol. After the first treatment period, the severity of
      symptoms and adenoid size decreased for 21 patients (77.7%) in group A. No
      improvement was observed in the placebo group. After 3 months of additional
      therapy, group A2 patients demonstrated a more-pronounced reduction in adenoid
      size compared with group A1 patients. No statistically significant change in
      symptoms was identified. Mometasone treatment was well tolerated by all patients.
      CONCLUSIONS: Mometasone furoate aqueous nasal spray may be considered useful in
      decreasing adenoid pad size and the severity of symptoms related to adenoidal
      hypertrophy. Children with adenoidal hypertrophy that is not associated with
      tonsillar hypertrophy should be considered for intranasal mometasone treatment
      before surgery is planned.

PMID- 17533177
TI  - Adherence to antiretroviral therapy for pediatric HIV infection: a qualitative
      systematic review with recommendations for research and clinical management.
AB  - Although nonadherence to prescribed therapies is widespread, it is particularly
      problematic with highly active antiretroviral therapy for HIV infection. This
      review of >50 studies in the area of pediatric HIV infection revealed varying
      methods for assessing antiretroviral adherence with a wide range of estimates of
      adherence. Correlates of adherence could be grouped as those relating to the
      medication, the patient, and the caregiver/family, with many conflicting findings
      and a lack of theory guiding the research. Only 8 studies, mainly small
      feasibility or pilot investigations, evaluated highly active antiretroviral
      therapy adherence interventions in pediatric populations. We conclude with
      specific recommendations for assessment and clinical management of adherence and
      discuss directions for future research in this area.

PMID- 17533179
TI  - Signal transducer and activator of transcription 1 is required for optimal foam
      cell formation and atherosclerotic lesion development.
AB  - BACKGROUND: Signal transducer and activator of transcription 1 (Stat1) potently
      regulates gene expression after stimulation by certain cytokines involved in
      tumorigenesis and host defenses. The present study investigated a novel role for
      Stat1 in foam cell formation and atherosclerosis. METHODS AND RESULTS: Inhibition
      of Stat1 activity by a Stat1-specific DNA "decoy" oligomer transfected into
      differentiated human THP-1 cells, and deficiency of stat1 in mouse macrophages
      significantly inhibited foam cell formation assessed by lipid staining and
      cholesteryl ester accumulation compared with control cells. The mechanism of
      Stat1 regulation of foam cell formation was uniquely dependent on the scavenger
      receptor CD36. Blunted Stat1 activity and stat1 deficiency significantly
      decreased expression of CD36 but not of scavenger receptor-A compared with
      controls, as assessed by immunoblotting and flow cytometry. Deficiency of CD36
      but not scavenger receptor-A in mouse macrophages removed any dependency of foam
      cell formation on Stat1. In an intraperitoneal model of foam cell formation in
      which foam cells form in vivo independently of the model ligands used in vitro,
      stat1 deficiency significantly inhibited foam cell formation and CD36 expression.
      Transplantation of bone marrow from apolipoprotein e-/- x stat1-/- mice into
      lethally irradiated, atherosclerosis-susceptible apolipoprotein e-/- recipients
      significantly reduced both en face aortic lesion coverage and aortic root lesions
      compared with recipients of bone marrow from genetically matched apolipoprotein e
      /- mice. CONCLUSIONS: Stat1 regulates CD36 expression and foam cell formation in
      macrophages in vitro; the Stat1 regulation of foam cell formation requires CD36.
      The regulation of CD36 expression by Stat1 may be important in other
      pathophysiological CD36-dependent events. Stat1 deficiency reduces
      atherosclerosis in an apolipoprotein e-/- atherosclerosis-susceptible bone marrow
      transplantation model.

PMID- 17533180
TI  - Loss of Mdm4 results in p53-dependent dilated cardiomyopathy.
AB  - BACKGROUND: Although several loci for familial dilated cardiomyopathy (DCM) have
      been mapped, the origin of a large percentage of DCM remains unclear. Mdm2, a p53
      negative regulator, protects cardiomyocytes from ischemic and reperfusion-induced
      cell death. Mdm4, a homolog of Mdm2, inhibits p53 activity in numerous cell
      types. It is unknown whether Mdm4 plays a role in the inhibition of p53 in fully
      differentiated tissues such as adult cardiomyocytes and whether this role is
      associated with DCM. METHODS AND RESULTS: The conditional knockout of Mdm4 in the
      heart by use of cardiomyocyte-specific Cre (alphaMyHC-Cre) allele does not result
      in any developmental defects. With time, however, mice with deletion of Mdm4 in
      the adult heart developed DCM and had a median survival of 234 days. More
      interestingly, the onset of DCM occurs significantly earlier in male mice than in
      female mice, which mimics human DCM disease. DCM in Mdm4 mutant mice was caused
      by loss of cardiomyocytes by apoptosis, and it was p53-dose dependent.
      CONCLUSION: Activity of p53 was inhibited by Mdm4 even in the fully
      differentiated cardiomyocyte. Elevated apoptosis mediated by the p53 pathway in
      cardiomyocytes may be a mechanism for DCM.

PMID- 17533181
TI  - Delta-like 4 induces notch signaling in macrophages: implications for
      inflammation.
AB  - BACKGROUND: Activated macrophages contribute to the pathogenesis of inflammatory
      diseases such as atherosclerosis. Although Notch signaling participates in
      various aspects of immunity, its role in macrophage activation remains
      undetermined. METHODS AND RESULTS: To explore the role of Notch signaling in
      inflammation, we examined the expression and activity of Notch pathway components
      in human primary macrophages in vitro and in atherosclerotic plaques. Macrophages
      in culture express various Notch pathway components including all 4 receptors
      (Notch1 to Notch4). Notch3 selectively increased during macrophage
      differentiation; however, silencing by RNA interference demonstrated that all
      receptors are functional. The ligand Delta-like 4 (Dll4) increased in macrophages
      exposed to proinflammatory stimuli such as lipopolysaccharide, interleukin-1beta,
      or minimally-modified low-density lipoprotein in a Toll-like receptor 4- and
      nuclear factor-kappaB-dependent fashion. Soluble Dll4 bound to human macrophages.
      Coincubation of macrophages with cells that expressed Dll4 triggered Notch
      proteolysis and activation; increased the transcription of proinflammatory genes
      such as inducible nitric oxide synthase, pentraxin 3 and Id1; resulted in
      activation of mitogen-activated protein kinase, Akt, and nuclear factor-kappaB
      pathways; and increased the expression of Dll4 in macrophages. Notch3 knockdown
      during macrophage differentiation decreased the transcription of genes that
      promote inflammation, such as inducible nitric oxide synthase, pentraxin 3, Id1,
      and scavenger receptor-A. These in vitro findings correlate with results of
      quantitative immunohistochemistry, which demonstrated the presence of Dll4 and
      other Notch components within macrophages in atherosclerotic plaques. CONCLUSION:
      Dll4-triggered Notch signaling may mediate inflammatory responses in macrophages
      and promote inflammation.

PMID- 17533182
TI  - Meta-analysis comparing the effectiveness and adverse outcomes of
      antifibrinolytic agents in cardiac surgery.
AB  - BACKGROUND: Since the 1980s, antifibrinolytic therapies have assisted surgical
      teams in reducing the amount of blood loss. To date, however, serious questions
      remain regarding the safety and effectiveness of these agents. METHODS AND
      RESULTS: We conducted a meta-analysis to compare aprotinin, epsilon-aminocaproic
      acid, and tranexamic acid with placebo and head to head on 8 clinical outcomes
      from 138 trials. Published randomized controlled trial data were collected from
      OVID/PubMed. Outcomes included total blood loss, transfusion of packed red blood
      cells, reexploration, mortality, stroke, myocardial infarction, dialysis
      dependent renal failure, and renal dysfunction (0.5-mg/dL increase in creatinine
      from baseline). All agents were effective in significantly reducing blood loss by
      226 to 348 mL and the proportion of patients transfused with packed red blood
      cells over placebo. Only high-dose aprotinin reduced the rate of reexploration
      (relative risk, 0.49; 95% CI, 0.33 to 0.73). There were no significant risks or
      benefits for any agent for mortality, stroke, myocardial infarction, or renal
      failure. However, high-dose aprotinin significantly increased the risk of renal
      dysfunction (relative risk, 1.47; 95% CI, 1.12 to 1.94), 12.9% versus 8.4%.
      Compared head to head, high-dose aprotinin demonstrated significant reduction in
      total blood loss over epsilon-aminocaproic acid (-184 mL; 95% CI, -256 to -112)
      and tranexamic acid (-195 mL; 95% CI, -286 to -105). There were no significant
      differences among any agent when compared head to head on other outcomes.
      CONCLUSIONS: All antifibrinolytic agents were effective in reducing blood loss
      and transfusion. There were no significant risks or benefits for mortality,
      stroke, myocardial infarction, or renal failure. However, high-dose aprotinin was
      associated with a statistically significant increased risk of renal dysfunction.

PMID- 17533183
TI  - Paradoxical low-flow, low-gradient severe aortic stenosis despite preserved
      ejection fraction is associated with higher afterload and reduced survival.
AB  - BACKGROUND: Recent studies and current clinical observations suggest that some
      patients with severe aortic stenosis on the basis of aortic valve area may
      paradoxically have a relatively low gradient despite the presence of a preserved
      left ventricular (LV) ejection fraction. The objective of the present study was
      to document the prevalence, potential mechanisms, and clinical relevance of this
      phenomenon. METHODS AND RESULTS: We retrospectively studied the clinical and
      Doppler echocardiographic data of 512 consecutive patients with severe aortic
      stenosis (indexed aortic valve area < or = 0.6 cm2 x m(-2)) and preserved LV
      ejection fraction (> or = 50%). Of these patients, 331 (65%) had normal LV flow
      output defined as a stroke volume index > 35 mL x m2, and 181 (35%) had
      paradoxically low-flow output defined as stroke volume index < or = 35 mL x m(
      2). When compared with normal flow patients, low-flow patients had a higher
      prevalence of female gender (P<0.05), a lower transvalvular gradient (32+/-17
      versus 40+/-15 mm Hg; P<0.001), a lower LV diastolic volume index (52+/-12 versus
      59+/-13 mL x m(-2); P<0.001), lower LV ejection fraction (62+/-8% versus 68+/-7%;
      P<0.001), a higher level of LV global afterload reflected by a higher valvulo
      arterial impedance (5.3+/-1.3 versus 4.1+/-0.7 mm Hg x mL(-1) x m(-2); P<0.001)
      and a lower overall 3-year survival (76% versus 86%; P=0.006). Only age (hazard
      ratio, 1.04; 95% CI, 1.01 to 1.08; P=0.025), valvulo-arterial impedance > 5.5 mm
      Hg x mL(-1) x m(-2) (hazard ratio, 2.6; 95% CI, 1.2 to 5.7; P=0.017), and medical
      treatment (hazard ratio, 3.3; 95% CI, 1.8 to 6.7; P=0.0003) were independently
      associated with increased mortality. CONCLUSION: Patients with severe aortic
      stenosis may have low transvalvular flow and low gradients despite normal LV
      ejection fraction. A comprehensive evaluation shows that this pattern is in fact
      consistent with a more advanced stage of the disease and has a poorer prognosis.
      Such findings are clinically relevant because this condition may often be
      misdiagnosed, which leads to a neglect and/or an underestimation of symptoms and
      an inappropriate delay of aortic valve replacement surgery.

PMID- 17533185
TI  - Twenty-five-year trends in in-hospital and long-term outcome after percutaneous
      coronary intervention: a single-institution experience.
AB  - BACKGROUND: Little is known about the impact of technological and pharmacological
      advances on long-term outcome after percutaneous coronary intervention in general
      clinical practice. METHODS AND RESULTS: We analyzed in-hospital and long-term
      outcome of 24,410 percutaneous coronary interventions among 18,575 unique
      patients who underwent percutaneous coronary intervention at Mayo Clinic over 25
      years. The study population was divided into group 1 (n=3708), coronary
      interventions from 1979 to 1989; group 2 (n=7020), interventions from 1990 to
      1996; group 3 (n=10,952), interventions from 1996 to 2003; and group 4 (n=2730),
      interventions from 2003 to 2004. Despite the fact that patients in groups 3 and 4
      were significantly older, sicker, and had greater prevalence of comorbid
      conditions, heart failure, and previous revascularization than those in groups 1
      and 2, procedural success in groups 3 and 4 improved significantly (94%) versus
      groups 2 (89%) and 1 (78%) (P<0.001). Significant reduction in in-hospital
      mortality (groups 4 to 1: 1.8%, 1.7%, 2.6%, 3.0%; P<0.001) and need for emergency
      bypass surgery (groups 4 to 1: 0.4%, 0.5%, 1.6%, 5%; P<0.001) was noted in groups
      3 and 4 compared with groups 1 and 2. Better adherence to currently recommended
      evidence-based medications for secondary prevention was seen in the recent time
      periods. After adjustment, significant reduction in follow-up mortality (hazard
      ratio, 0.81 and 0.74 for groups 3 and 4, respectively); death or myocardial
      infarction (hazard ratio, 0.80 and 0.75 for groups 3 and 4, respectively); death,
      myocardial infarction, or revascularization (hazard ratio, 0.76 and 0.58 for
      groups 3 and 4, respectively) was noted in recent time periods. CONCLUSIONS:
      Despite higher-risk profiles of patients who underwent percutaneous coronary
      intervention in recent time periods, procedural success as well as in-hospital
      and long-term outcomes improved significantly over the last 25 years.

PMID- 17533184
TI  - Associations of plasma natriuretic peptide, adrenomedullin, and homocysteine
      levels with alterations in arterial stiffness: the Framingham Heart Study.
AB  - BACKGROUND: Increased arterial stiffness and higher plasma natriuretic peptide
      and homocysteine levels are associated with elevated risk for cardiovascular
      disease. Little is known about the relations of natriuretic peptides and
      homocysteine to arterial wall stiffness in the community. METHODS AND RESULTS: We
      assessed the relations of plasma N-terminal atrial natriuretic peptide, B-type
      natriuretic peptide, adrenomedullin, and homocysteine concentrations to arterial
      stiffness in participants in the Framingham Heart Study. Central pulse pressure,
      forward pressure wave, reflected pressure wave, carotid-femoral pulse wave
      velocity, and carotid-radial pulse wave velocity were assessed by tonometry in
      1962 participants (mean age, 61 years; 56% women) in the Framingham Heart Study.
      Central systolic and diastolic blood pressures were 123/75 mm Hg in men and
      119/66 mm Hg in women. After adjustment for age and clinical covariates, N
      terminal atrial natriuretic peptide and B-type natriuretic peptide were
      associated with carotid-femoral pulse wave velocity (men: partial correlation,
      0.069, P = 0.043 and r = 0.115, P < or = 0.001, respectively; women: r = -0.063,
      P = 0.037 and r = -0.062, P = 0.040), and carotid-radial pulse wave velocity
      (men: r = -0.090, P = 0.009 and r = -0.083, P < or = 0.015; women: r = -0.140, P
      < or = 0.001 and r = -0.104, P = 0.001, respectively). In men, N-terminal atrial
      natriuretic peptide and B-type natriuretic peptide also were associated with
      forward and reflected wave and carotid pulse pressure. In men, adrenomedullin was
      associated with mean arterial pressure (r = 0.089, P = 0.009), and homocysteine
      was associated with carotid-femoral pulse wave velocity (r = 0.072, P = 0.036),
      forward pressure (r = 0.079, P = 0.02), and central pulse pressure (r = 0.072, P
      = 0.035). Interaction tests indicated sex differences in the relations of several
      biomarkers to measures of arterial stiffness. CONCLUSIONS: Plasma natriuretic
      peptide, adrenomedullin, and homocysteine levels are associated with alterations
      in conduit vessel properties that differ in men and women.

PMID- 17533186
TI  - Images in cardiovascular medicine. Intracardiac correlate of the epsilon wave in
      a patient with arrhythmogenic right ventricular dysplasia.

PMID- 17533187
TI  - Images in cardiovascular medicine. Loculated pericardial hematoma complicating
      complex coronary interventions: a rare but often missed diagnosis?

PMID- 17533188
TI  - Images in cardiovascular medicine. Percutaneous pericardial access for mapping
      and ablation of epicardial ventricular tachycardias.

PMID- 17533189
TI  - Letter by Wiggers et al regarding article by Tuunanen et al, "Free fatty acid
      depletion acutely decreases cardiac work and efficiency in cardiomyopathic heart
      failure".

PMID- 17533190
TI  - Letter by Fragasso et al regarding article by Tuunanen et al, "Free fatty acid
      depletion acutely decreases cardiac work and efficiency in cardiomyopathic heart
      failure".

PMID- 17533191
TI  - Letter by Pascual-Figal et al regarding article, "Anabolic deficiency in men with
      chronic heart failure: prevalence and detrimental impact on survival".

PMID- 17533192
TI  - Spotlight: Massimo Mariani, MD, PhD, FECTS. Interview by Mark Nicholls.

PMID- 17533193
TI  - Bleeding while starting anticoagulation for thromboembolism prophylaxis in
      elderly patients with atrial fibrillation: from bad to worse.

PMID- 17533194
TI  - Through thick and thin collagen fibrils, stress, and aortic rupture: another
      piece in the jigsaw.

PMID- 17533195
TI  - Catheter ablation for ventricular tachycardia.

PMID- 17533197
TI  - Selection bias, confounding, or information bias?

PMID- 17533198
TI  - Aldosterone: villain or protector?

PMID- 17533199
TI  - NADPH oxidase contributes to vascular inflammation, insulin resistance, and
      remodeling in the transgenic (mRen2) rat.
AB  - Reduced insulin sensitivity is characteristic of various pathological conditions
      such as type 2 diabetes mellitus and hypertension. Angiotensin II, acting through
      its angiotensin type 1 receptor, inhibits the actions of insulin in the
      vasculature which may lead to deleterious effects such as vascular inflammation,
      remodeling, endothelial dysfunction, and insulin resistance. In contrast, insulin
      normally exerts vasodilatory, antiinflammatory, and prosurvival actions. To
      explore the impact of angiotensin II on insulin signaling, NADPH oxidase-derived
      reactive oxygen species formation, vascular inflammation, apoptosis, and
      remodeling, we used transgenic TG(mRen2)27 (Ren2) rats, which harbor the mouse
      renin transgene and exhibits elevated tissue angiotensin II levels. Compared with
      Sprague-Dawley controls, Ren2 aortas exhibited greater NADPH oxidase activity,
      reactive oxygen species levels, C-reactive protein, tumor necrosis factor-alpha
      expression, apoptosis, and wall thickness, which were significantly attenuated by
      in vivo treatment with angiotensin type 1 receptor blockade (valsartan) or the
      superoxide dismutase/catalase mimetic (tempol). There was substantially
      diminished Akt and endothelial NO synthase activation in Ren2 aortas in response
      to in vivo insulin stimulation, and this was significantly improved by in vivo
      treatment with valsartan or tempol. In vivo treatment with valsartan, but not
      tempol, significantly reduced blood pressure in Ren2 rats. Further, there was
      reduced insulin induced Akt activation and increased tumor necrosis factor-alpha
      levels in vascular smooth muscle cells from Ren2 and Sprague-Dawley rats treated
      with angiotensin II, abnormalities that were abrogated by angiotensin type 1
      receptor blockade with valsartan or antioxidant N-acetylcysteine. Collectively,
      these data suggest that increased angiotensin type 1 receptor/NADPH oxidase
      activation/reactive oxygen species contribute to vascular insulin resistance,
      endothelial dysfunction, apoptosis, and inflammation.

PMID- 17533200
TI  - Translating evidence into practice: are we neglecting the neediest?

PMID- 17533201
TI  - Adult bone marrow-derived cells for cardiac repair: a systematic review and meta
      analysis.
AB  - BACKGROUND: The results from small clinical studies suggest that therapy with
      adult bone marrow (BM)-derived cells (BMCs) reduces infarct size and improves
      left ventricular function and perfusion. However, the effects of BMC
      transplantation in patients with ischemic heart disease remains unclear. METHODS:
      We searched MEDLINE, EMBASE, Science Citation Index, CINAHL (Cumulative Index to
      Nursing and Allied Health), and the Cochrane Central Register of Controlled
      Trials (CENTRAL) (through July 2006) for randomized controlled trials and cohort
      studies of BMC transplantation to treat ischemic heart disease. We conducted a
      random-effects meta-analysis across eligible studies measuring the same outcomes.
      RESULTS: Eighteen studies (N = 999 patients) were eligible. The adult BMCs
      included BM mononuclear cells, BM mesenchymal stem cells, and BM-derived
      circulating progenitor cells. Compared with controls, BMC transplantation
      improved left ventricular ejection fraction (pooled difference, 3.66%; 95%
      confidence interval [CI], 1.93% to 5.40%; P<.001); reduced infarct scar size (
      5.49%; 95% CI, -9.10% to -1.88%; P = .003); and reduced left ventricular end
      systolic volume (-4.80 mL; 95% CI, -8.20 to -1.41 mL; P = .006). CONCLUSIONS: The
      available evidence suggests that BMC transplantation is associated with modest
      improvements in physiologic and anatomic parameters in patients with both acute
      myocardial infarction and chronic ischemic heart disease, above and beyond
      conventional therapy. Therapy with BMCs seems safe. These results support
      conducting large randomized trials to evaluate the impact of BMC therapy vs the
      standard of care on patient-important outcomes.

PMID- 17533202
TI  - Effect of aerobic exercise training on serum levels of high-density lipoprotein
      cholesterol: a meta-analysis.
AB  - BACKGROUND: Aerobic exercise is believed to reduce the risk of cardiovascular
      disease partially through increasing serum levels of high-density lipoprotein
      cholesterol (HDL-C). However, this effect varies considerably among exercise
      intervention studies. METHODS: Electronic database searches of MEDLINE (1966
      2005) for randomized controlled trials that examined the effect of exercise
      training on HDL-C level. RESULTS: Twenty-five articles were included. Mean net
      change in HDL-C level was statistically significant but modest (2.53 mg/dL [0.065
      mmol/L]; P<.001). Minimal weekly exercise volume for increasing HDL-C level was
      estimated to be 900 kcal of energy expenditure per week or 120 minutes of
      exercise per week. Univariate regression analysis indicated that every 10-minute
      prolongation of exercise per session was associated with an approximately 1.4
      mg/dL (0.036-mmol/L) increase in HDL-C level. In contrast, there was no
      significant association between exercise frequency or intensity. Multiple meta
      regression analyses demonstrated that subjects with a body mass index (calculated
      as weight in kilograms divided by height in meters squared) less than 28 and
      total cholesterol level of 220 mg/dL [5.7 mmol/L] or more experienced an
      approximately 2.1-mg/dL (0.054-mmol/L) larger increase in HDL-C level than those
      with a body mass index of 28 or more and total cholesterol level less than 220
      mg/dL (5.7 mmol/L). CONCLUSIONS: Regular aerobic exercise modestly increases HDL
      C level. There appears to exist a minimum exercise volume for a significant
      increase in HDL-C level. Exercise duration per session was the most important
      element of an exercise prescription. Exercise was more effective in subjects with
      initially high total cholesterol levels or low body mass index.

PMID- 17533203
TI  - Management patterns in relation to risk stratification among patients with non-ST
      elevation acute coronary syndromes.
AB  - BACKGROUND: Randomized clinical trials have established the efficacy of an early
      invasive management strategy for high-risk non-ST elevation acute coronary
      syndromes (ACSs). We examined the use of in-hospital cardiac catheterization and
      medications in relation to risk across the broad spectrum of non-ST elevation
      ACSs. METHODS: We evaluated 4414 patients with non-ST elevation ACSs in the
      prospective, multicenter, Canadian ACS 1 (September 1, 1999-June 30, 2001) and
      ACS 2 (October 1, 2002-December 31, 2003) Registries. Patients were stratified
      into low-, intermediate-, and high-risk groups based on tertiles of the
      calculated Global Registry of Acute Coronary Events risk score (a validated
      predictor of in-hospital mortality). RESULTS: Although in-hospital mortality
      rates were similar, the in-hospital use of cardiac catheterization increased
      significantly over time (38.8% in the ACS 1 Registry vs 63.5% in the ACS 2
      Registry; P<.001). The rates of cardiac catheterization in the low-, intermediate
      , and high-risk groups were 48.0%, 41.1%, and 27.3% in the ACS 1 Registry, and
      73.8%, 66.9%, and 49.7% in the ACS 2 Registry, respectively (P<.001 for trend for
      both). After adjusting for other confounders, intermediate-risk (adjusted odds
      ratio, 0.75; 95% confidence interval, 0.63-0.90; P<.001) and high-risk (adjusted
      odds ratio, 0.35; 95% confidence interval, 0.28-0.45; P<.001) patients remained
      less likely to undergo cardiac catheterization compared with low-risk patients.
      Furthermore, there existed a similar inverse relationship between risk and the
      use of in-hospital revascularization and medications. CONCLUSIONS: Despite
      temporal increases in the use of cardiac catheterization and revascularization in
      the management of non-ST elevation ACSs, evidence-based invasive and
      pharmacological therapies remain paradoxically targeted toward low-risk patients.
      Strategies to eliminate this treatment-risk paradox must be implemented to fully
      realize the benefits and optimize the cost-effectiveness of invasive management.

PMID- 17533204
TI  - Exploring the treatment-risk paradox in coronary disease.
AB  - BACKGROUND: The cause of the "treatment-risk paradox" reported for patients with
      coronary disease is unknown; however, determining the factors that contribute to
      this paradox is essential to properly design quality improvement interventions.
      METHODS: Prospective cohort study enrolling consecutive patients with
      angiographically proved coronary disease between February 1, 2004, and November
      30, 2005, in Alberta. RESULTS: One month after an angiogram, statins were being
      taken by 2436 (62.9%) of 3871 patients (mean age, 64 years). High-risk patients
      were less likely to be taking statins than lower-risk patients (55.8% vs 63.5%;
      crude odds ratio [OR], 0.72 [95% confidence interval {CI}, 0.57-0.92]; risk ratio
      [RR], 0.88 [95% CI, 0.79-0.97]), but this treatment-risk paradox was completely
      attenuated by adjusting for exertional capacity and depressive symptoms (OR, 0.98
      [95% CI, 0.75-1.28]; RR, 0.99 [95% CI, 0.89-1.09]). These results were robust
      across drug classes: while high-risk patients were less likely to be taking
      angiotensin-converting enzyme inhibitors, aspirin, and statins (25.8% vs 32.3%;
      crude OR, 0.73 [95% CI, 0.56-0.95]; RR, 0.80 [95% CI, 0.65-0.97]), this
      association did not persist in the adjusted model (OR, 0.98 [95% CI, 0.72-1.33]
      [P = .87]; RR, 0.99 [95% CI, 0.79-1.20]). CONCLUSIONS: The treatment-risk paradox
      reported in administrative database analyses is attributable to clinical factors
      not typically captured in these databases (such as functional capacity and
      depressive symptoms). Interventions to address the treatment-risk paradox should
      recognize that patients with reduced functional capacity, depression, or both are
      at higher risk for underuse of these beneficial therapies and should target
      physicians and patients.

PMID- 17533205
TI  - Community-associated methicillin-resistant Staphylococcus aureus skin and soft
      tissue infections at a public hospital: do public housing and incarceration
      amplify transmission?
AB  - BACKGROUND: Community-associated methicillin-resistant Staphylococcus aureus (CA
      MRSA) infections have emerged among patients without health care-associated risk
      factors. Understanding the epidemiology of CA-MRSA is critical for developing
      control measures. METHODS: At a 464-bed public hospital in Chicago and its more
      than 100 associated clinics, surveillance of soft tissue, abscess fluid, joint
      fluid, and bone cultures for S aureus was performed. We estimated rates of
      infection and geographic and other risks for CA-MRSA through laboratory-based
      surveillance and a case-control study. RESULTS: The incidence of CA-MRSA skin and
      soft tissue infections increased from 24.0 cases per 100,000 people in 2000 to
      164.2 cases per 100,000 people in 2005 (relative risk, 6.84 [2005 vs 2000]). Risk
      factors were incarceration (odds ratio [OR], 1.92; 95% confidence interval [CI],
      1.00-3.67), African American race/ethnicity (OR, 1.91; 95% CI, 1.28-2.87), and
      residence at a group of geographically proximate public housing complexes (OR,
      2.50; 95% CI, 1.25-4.98); older age was inversely related (OR, 0.89; 95% CI, 0.82
      0.96 [for each decade increase]). Of 73 strains tested, 79% were pulsed-field gel
      electrophoresis type USA300. CONCLUSIONS: Clonal CA-MRSA infection has emerged
      among Chicago's urban poor. It has occurred in addition to, not in place of,
      methicillin-susceptible S aureus infection. Epidemiological analysis suggests
      that control measures could focus initially on core groups that have contributed
      disproportionately to risk, although CA-MRSA becomes endemic as it disseminates
      within communities.

PMID- 17533206
TI  - Pharmacist medication assessments in a surgical preadmission clinic.
AB  - BACKGROUND: In the hospital setting, postoperative admission is a key vulnerable
      moment when patients are at increased risk of medication discrepancies. This
      study measures the reduction of medication discrepancies associated with a
      combined intervention of structured pharmacist medication history interviews with
      assessments in a surgical preadmission clinic and a postoperative medication
      order form. METHODS: In the Surgical Pharmacist in Preadmission Clinic Evaluation
      (SPPACE) study, patients who had a preadmission clinic appointment before
      undergoing surgical procedures were eligible for inclusion. Patients were
      excluded if they were scheduled for discharge the same day as their surgery.
      Eligible patients were randomly assigned to the intervention arm (structured
      pharmacist medication history interview with assessment and generation of a
      postoperative medication order form) or to the standard care arm (nurse-conducted
      medication histories and surgeon-generated medication orders). The primary end
      point was the number of patients with at least 1 postoperative medication
      discrepancy related to home medications. RESULTS: Between April 19, 2005, and
      June 3, 2005, a total of 464 patients were enrolled in the study, of which 227
      and 237 patients were randomized to the intervention and standard care arms,
      respectively. In the intervention arm, 41 (20.3%) of 202 patients had at least 1
      postoperative medication discrepancy related to home medications, compared with
      86 (40.2%) of 214 patients in the standard care arm (P<.001). In the intervention
      arm, 26 (12.9%) of 202 patients had at least 1 postoperative medication
      discrepancy with the potential to cause possible or probable harm, compared with
      64 (29.9%) of 214 patients in the standard care arm (P<.001). These were mostly
      omissions of reordering home medications. CONCLUSION: A combined intervention of
      pharmacist medication assessments and a postoperative medication order form can
      reduce postoperative medication discrepancies related to home medications.

PMID- 17533207
TI  - Evaluation of serious adverse drug reactions: a proactive pharmacovigilance
      program (RADAR) vs safety activities conducted by the Food and Drug
      Administration and pharmaceutical manufacturers.
AB  - BACKGROUND: The Food and Drug Administration (FDA) and pharmaceutical
      manufacturers conduct most postmarketing pharmaceutical safety investigations.
      These efforts are frequently based on data mining of databases. In 1998,
      investigators initiated the Research on Adverse Drug events And Reports (RADAR)
      project to investigate reports of serious adverse drug reactions (ADRs) and
      prospectively obtain information on these cases. We compare safety efforts for
      evaluating serious ADRs conducted by the FDA and pharmaceutical manufacturers vs
      the RADAR project. METHODS: We evaluated the completeness of serious ADR
      descriptions in the FDA and RADAR databases and the comprehensiveness of
      notifications disseminated by pharmaceutical manufacturers and the RADAR
      investigators. A serious ADR was defined as an event that led to death or
      required intensive therapies to reverse. RESULTS: The RADAR investigators
      evaluated 16 serious ADRs. Compared with descriptions of these ADRs in FDA
      databases (2296 reports), reports in RADAR databases (472 reports) had a 2-fold
      higher rate of including information on history and physical examination (92% vs
      45%; P<.001) and a 9-fold higher rate of including basic science findings (34% vs
      4%; P = .08). Safety notifications were disseminated earlier by pharmaceutical
      suppliers (2 vs 4 years after approval, respectively), although notifications
      were less likely to include information on incidence (46% vs 93%; P = .02),
      outcomes (8% vs 100%; P<.001), treatment or prophylaxis (25% vs 93%; P<.001), or
      references (8% vs 80%; P<.001). CONCLUSION: Proactive safety efforts conducted by
      the RADAR investigators are more comprehensive than those conducted by the FDA
      and pharmaceutical manufacturers, but dissemination of related safety
      notifications is less timely.

PMID- 17533208
TI  - Intakes of calcium and vitamin D and breast cancer risk in women.
AB  - BACKGROUND: Animal data suggest the potential anticarcinogenic effects of calcium
      and vitamin D on breast cancer development. However, epidemiologic data relating
      calcium and vitamin D levels to breast cancer have been inconclusive. METHODS: We
      prospectively evaluated total calcium and vitamin D intake in relation to breast
      cancer incidence among 10,578 premenopausal and 20,909 postmenopausal women 45
      years or older who were free of cancer and cardiovascular disease at baseline in
      the Women's Health Study. Baseline dietary intake was assessed by a food
      frequency questionnaire. We used Cox proportional hazards regression to estimate
      hazard ratios and 95% confidence intervals. RESULTS: During an average of 10
      years of follow-up, 276 premenopausal and 743 postmenopausal women had a
      confirmed diagnosis of incident invasive breast cancer. Higher intakes of total
      calcium and vitamin D were moderately associated with a lower risk of
      premenopausal breast cancer; the hazard ratios in the group with the highest
      relative to the lowest quintile of intake were 0.61 (95% confidence interval,
      0.40-0.92) for calcium (P = .04 for trend) and 0.65 (95% confidence interval,
      0.42-1.00) for vitamin D intake (P = .07 for trend). The inverse association with
      both nutrients was also present for large or poorly differentiated breast tumors
      among premenopausal women (P< or =.04 for trend). By contrast, intakes of both
      nutrients were not inversely associated with the risk of breast cancer among
      postmenopausal women. CONCLUSIONS: Findings from this study suggest that higher
      intakes of calcium and vitamin D may be associated with a lower risk of
      developing premenopausal breast cancer. The likely apparent protection in
      premenopausal women may be more pronounced for more aggressive breast tumors.

PMID- 17533209
TI  - Effect of soy nuts on blood pressure and lipid levels in hypertensive,
      prehypertensive, and normotensive postmenopausal women.
AB  - BACKGROUND: Epidemiologic studies suggest a low incidence of cardiovascular
      disease in populations that consume dietary soy. For people aged 40 to 70 years,
      each increment of 20 mm Hg in systolic blood pressure (BP) or 10 mm Hg in
      diastolic BP doubles the risk of cardiovascular disease for BPs of 115/75 to
      185/115 mm Hg. METHODS: To determine the effect of soy nuts on systolic and
      diastolic BP and lipid levels, 60 healthy postmenopausal women were randomized in
      a crossover design to a Therapeutic Lifestyle Changes (TLC) diet alone and a TLC
      diet of similar energy, fat, and protein content in which soy nuts (containing 25
      g of soy protein and 101 mg of aglycone isoflavones) replaced 25 g of non-soy
      protein. Each diet was followed for 8 weeks. RESULTS: Compared with the TLC diet
      alone, the TLC diet plus soy nuts lowered systolic and diastolic BP 9.9% and
      6.8%, respectively, in hypertensive women (systolic BP> or =140 mm Hg) and 5.2%
      and 2.9%, respectively, in normotensive women (systolic BP<120 mm Hg). Further
      subdivision of normotensive women revealed that systolic and diastolic BPs were
      lowered 5.5% and 2.7%, respectively, in prehypertensive women (systolic BP of 120
      139 mm Hg) and 4.5% and 3.0%, respectively, in normotensive women. Soy nut
      supplementation lowered low-density lipoprotein cholesterol and apolipoprotein B
      levels 11% and 8% (P = .04 for both), respectively, in hypertensive women but had
      no effect in normotensive women. CONCLUSIONS: Substituting soy nuts for nonsoy
      protein in a TLC diet improves BP and low-density lipoprotein cholesterol levels
      in hypertensive women and BP in normotensive postmenopausal women. These findings
      may explain a cardioprotective effect of soy.

PMID- 17533210
TI  - Prediction of incident diabetes mellitus in middle-aged adults: the Framingham
      Offspring Study.
AB  - BACKGROUND: Prediction rules for type 2 diabetes mellitus (T2DM) have been
      developed, but we lack consensus for the most effective approach. METHODS: We
      estimated the 7-year risk of T2DM in middle-aged participants who had an oral
      glucose tolerance test at baseline. There were 160 cases of new T2DM, and
      regression models were used to predict new T2DM, starting with characteristics
      known to the subject (personal model, ie, age, sex, parental history of diabetes,
      and body mass index [calculated as the weight in kilograms divided by height in
      meters squared]), adding simple clinical measurements that included metabolic
      syndrome traits (simple clinical model), and, finally, assessing complex clinical
      models that included (1) 2-hour post-oral glucose tolerance test glucose, fasting
      insulin, and C-reactive protein levels; (2) the Gutt insulin sensitivity index;
      or (3) the homeostasis model insulin resistance and the homeostasis model insulin
      resistance beta-cell sensitivity indexes. Discrimination was assessed with area
      under the receiver operating characteristic curves (AROCs). RESULTS: The personal
      model variables, except sex, were statistically significant predictors of T2DM
      (AROC, 0.72). In the simple clinical model, parental history of diabetes and
      obesity remained significant predictors, along with hypertension, low levels of
      high-density lipoprotein cholesterol, elevated triglyceride levels, and impaired
      fasting glucose findings but not a large waist circumference (AROC, 0.85).
      Complex clinical models showed no further improvement in model discriminations
      (AROC, 0.850-0.854) and were not superior to the simple clinical model.
      CONCLUSION: Parental diabetes, obesity, and metabolic syndrome traits effectively
      predict T2DM risk in a middle-aged white population sample and were used to
      develop a simple T2DM prediction algorithm to estimate risk of new T2DM during a
      7-year follow-up interval.

PMID- 17533211
TI  - Helping patients with type 2 diabetes mellitus make treatment decisions: statin
      choice randomized trial.
AB  - BACKGROUND: Poor quality of information transfer about the benefits and risks of
      statin drug use may result in patients not making informed decisions that they
      can act on in a timely fashion. METHODS: The effect of a decision aid about
      statin drugs on treatment decision making in 98 patients with diabetes was
      determined in a cluster randomized trial of decision aid vs control pamphlet,
      with concealed allocation, blinding of participants to study goals, and adherence
      to the intention-to-treat principle. Twenty-one endocrinologists conducted
      specialty outpatient metabolic consultations. Patients in the intervention group
      received Statin Choice, a tailored decision aid that presents the estimated 10
      year cardiovascular risk, the absolute risk reduction with use of statin drugs,
      and the disadvantages of using statin drugs. Patients in the control group
      received the institution's pamphlet about cholesterol management. We measured
      acceptability, knowledge about options and cardiovascular risk, and decisional
      conflict immediately after the visit, and adherence to pill taking was measured 3
      months later. RESULTS: Patients favored using the decision aid (odds ratio [OR],
      2.8; 95% confidence interval [CI], 1.2-6.9); patients who received the decision
      aid (n = 52) knew more (difference, 2.4 of 9 points; 95% CI, 1.5-3.3), had better
      estimated cardiovascular risk (OR, 22.4; 95% CI, 5.9-85.6) and potential absolute
      risk reduction with statin drugs (OR, 6.7; 95% CI, 2.2-19.7), and had less
      decisional conflict (difference, -10.6; 95% CI, -15.4 to -5.9 on a 100-point
      scale) than did patients in the control group (n = 46). Of 33 patients in the
      intervention group taking statin drugs at 3 months, 2 reported missing 1 dose or
      more in the last week compared with 6 of 29 patients in the control group taking
      statin drugs (OR, 3.4; 95% CI, 1.5-7.5). CONCLUSIONS: A decision aid enhanced
      decision making about statin drugs and may have favorably affected drug
      adherence.

PMID- 17533212
TI  - Laboratory abnormalities at the onset of treatment of end-stage renal disease:
      are there racial or socioeconomic disparities in care?
AB  - BACKGROUND: Laboratory abnormalities at the start of treatment of end-stage renal
      disease (ESRD) have been reported as worse in racial/ethnic minorities than in
      white patients, suggesting racial disparities in care. It is not known whether
      these differences are attributable to racial/ethnic differences in socioeconomic
      status (SES). METHODS: We tested associations between race/ethnicity, SES, and
      type of medical insurance and serum creatinine level, estimated glomerular
      filtration rate, serum albumin level, and hematocrit at the start of treatment of
      ESRD and use of epoietin before ESRD treatment in a large national population
      based sample. Data on 515 561 patients beginning ESRD treatment between January
      1, 1996, and June 30, 2004, were obtained for this cross-sectional survey from
      the United States Renal Data System. RESULTS: Race/ethnicity had a much stronger
      association than SES with each laboratory measure. Adjusted mean serum creatinine
      levels were lowest in white patients (7.5 mg/dL [663.0 micromol/L]; 95%
      confidence interval [CI], 7.45-7.49) and highest in black patients (8.9 mg/dL
      [786.7 micromol/L]; 95% CI, 8.92-8.97) (P<.001 across racial/ethnic groups).
      Adjusted mean hematocrit for white patients (29.5%; 95% CI, 29.4%-29.6%) was
      significantly higher and for black patients (28.3%; 95% CI, 28.2%-28.4%)
      significantly lower than that of all other racial/ethnic groups (P<.001 across
      racial/ethnic groups). Less marked differences were present for estimated
      glomerular filtration rate and serum albumin level. In contrast, predialysis use
      of epoietin was associated with race/ethnicity (black vs white: odds ratio, 0.80;
      95% CI, 0.78-0.81; Hispanic vs white: odds ratio, 0.87; 95% CI, 0.85-0.89) and
      showed a graded decrease with decreasing SES (odds ratio for the lowest vs
      highest socioeconomic quartile 0.68; 95% CI, 0.67-0.70). Patients without medical
      insurance had more abnormal laboratory values than those with insurance, but
      these associations were weaker than those of race/ethnicity. CONCLUSIONS:
      Minorities, particularly black patients, had more severe laboratory abnormalities
      at the start of ESRD treatment than white patients. These differences were not
      readily attributable to SES differences. Absence of medical insurance, SES, and
      race/ethnicity were associated with the likelihood of predialysis use of
      epoietin.

PMID- 17533213
TI  - Evaluation of Clostridium difficile-associated disease pressure as a risk factor
      for C difficile-associated disease.
AB  - BACKGROUND: Colonization pressure has been identified as an important risk factor
      in the transmission of methicillin-resistant Staphylococcus aureus and vancomycin
      resistant Enterococcus species, but the role of colonization pressure in the
      transmission of Clostridium difficile-associated disease (CDAD) is unclear. The
      purpose of this study was to evaluate CDAD pressure, a modified form of
      colonization pressure based on symptomatic CDAD cases, as a risk factor for CDAD.
      METHODS: Retrospective cohort and nested case-control studies of patients
      admitted to Barnes-Jewish Hospital from January 1, 2003, through December 31,
      2003. Univariate analysis and multivariate logistic regression models were used
      to evaluate the role of CDAD pressure as a risk factor for CDAD. RESULTS: A total
      of 36 275 patients were included in the cohort, of which 382 had CDAD. The median
      CDAD pressure was higher for case patients than noncase patients (1.4 vs 0.3;
      P<.001), and only 1 patient with CDAD had a CDAD pressure of 0. In the nested
      case-control study, CDAD pressure remained an independent risk factor for CDAD
      after adjustment for demographics, severity of illness, medications received
      (chemotherapy, gastric acid suppressors, antidiarrheals or narcotics, and
      antibiotics), and abdominal procedures or surgery performed. CONCLUSIONS: The
      results of this study suggest that CDAD pressure may be an independent risk
      factor for CDAD. Future studies that evaluate risk of CDAD should control for
      CDAD pressure.

PMID- 17533214
TI  - Decreased sleep in heart failure: are medications to blame?

PMID- 17533215
TI  - Cognitive declines therapy by iron burden reduction.

PMID- 17533216
TI  - The role of statins in primary prevention of cardiovascular disease.

PMID- 17533217
TI  - NADPH production by the pentose phosphate pathway in the zona fasciculata of rat
      adrenal gland.
AB  - Biosynthesis of steroid hormones in the cortex of the adrenal gland takes place
      in smooth endoplasmic reticulum and mitochondria and requires NADPH. Four enzymes
      produce NADPH: glucose-6-phosphate dehydrogenase (G6PD), the key regulatory
      enzyme of the pentose phosphate pathway, phosphogluconate dehydrogenase (PGD),
      the third enzyme of that pathway, malate dehydrogenase (MDH), and isocitrate
      dehydrogenase (ICDH). However, the contribution of each enzyme to NADPH
      production in the cortex of adrenal gland has not been established. Therefore,
      activity of G6PD, PGD, MDH, and ICDH was localized and quantified in rat
      adrenocortical tissue using metabolic mapping, image analysis, and electron
      microscopy. The four enzymes have similar localization patterns in adrenal gland
      with highest activities in the zona fasciculata of the cortex. G6PD activity was
      strongest, PGD, MDH, and ICDH activity was approximately 60%, 15%, and 7% of G6PD
      activity, respectively. The K(m) value of G6PD for glucose-6-phosphate was two
      times higher than the K(m) value of PGD for phosphogluconate. As a consequence,
      virtual flux rates through G6PD and PGD are largely similar. It is concluded that
      G6PD and PGD provide the major part of NADPH in adrenocortical cells. Their
      activity is localized in the cytoplasm associated with free ribosomes and
      membranes of the smooth endoplasmic reticulum, indicating that NADPH-demanding
      processes related to biosynthesis of steroid hormones take place at these sites.
      Complete inhibition of G6PD by androsterones suggests that there is feedback
      regulation of steroid hormone biosynthesis via G6PD.

PMID- 17533218
TI  - Beta-catenin (CTNNB1) in the mouse uterus during decidualization and the
      potential role of two pathways in regulating its degradation.
AB  - Beta-catenin plays a role in cell adhesion and as a transcriptional coactivator.
      Its levels are regulated in cells by controlling its degradation through
      ubiquitination by two different E3 ligase complexes. One complex contains beta
      transducing repeat containing (BTRC) protein, which binds to beta-catenin when
      phosphorylated on specific (S33 and S37) residues, whereas the other involves
      calcyclin-binding protein (CACYBP). The aim of this study was to determine the
      localization and levels of total and active (S33/S37-dephosphorylated) beta
      catenin in the pregnant mouse uteri and those undergoing artificially stimulated
      decidualization. These two forms of beta-catenin were localized almost
      exclusively to the endometrial epithelia just prior to the onset of implantation.
      Although this localization continued after the onset of implantation, there were
      less epithelial cells present in areas of the uterus undergoing decidualization.
      Rather, there was a progressive increase in beta-catenin localization in
      endometrial stromal cells undergoing decidualization in the anti-mesometrial and,
      to a lesser extent, in the mesometrial regions. The presence of a conceptus was
      not required for the changes in localization seen in the pregnant uterus because
      similar findings were also seen in uteri undergoing artificially stimulated
      decidualization. Finally, overall levels of total, active (S33 and S37
      dephosphorylated), and phosphorylated (S33/S37/T42) beta-catenin protein and the
      steady-state levels of calcyclin-binding protein mRNA changed in the uterus
      during decidualization. The result of this study shows the changing localization
      and levels of beta-catenin in the mouse uterus during decidualization. Further,
      the results suggest potential roles for both the BTRC and CACYBP E3 ligase
      mechanisms of beta-catenin ubiquitination in the uterus during decidualization.

PMID- 17533219
TI  - Novel DNA staining method and processing technique for the quantification of
      undamaged double-stranded DNA in epidermal tissue sections by PicoGreen probe
      staining and microspectrophotometry.
AB  - Histotechnological processing of DNA can cause damage to and loss of DNA and can
      change its structure. DNA probes have severe tissue-staining limitations. New DNA
      probes and improved histotechnology are needed to enhance the characterization of
      fixed tissue-bound DNA. Our team developed a novel DNA staining technique and
      histotechnological processing procedure that improves tissue-bound DNA retention
      and the qualification and quantification of intact double-stranded (ds)-B-DNA. We
      used the ultrasensitive PicoGreen ds-DNA probe for the histochemical
      characterization of ds-DNA. Fifteen fixatives were examined to determine which
      were best for preventing DNA denaturation and retaining original DNA content and
      structures. Our use of a microwave-vacuum oven reduced heating temperatures,
      shortened heating and processing times, and enhanced fixation. We achieved better
      qualitative and quantitative results by using superior tissue-acquisition
      techniques (e.g., reduced prefixation times) and improved histotechnology. We
      also compared our novel approach with archival tissues, delayed fixation, less
      sophisticated and conventional histological processing techniques, and by
      experimenting with preservation of tissue-bound ds-Z-DNA. Results demonstrate
      that our histotechnological procedure and nucleic acid staining method
      significantly improve the retention of intact, undamaged ds-DNA which, in turn,
      allows the investigator to more precisely quantify the content and structures of
      unaltered and undamaged tissue-bound ds-B-DNA.

PMID- 17533220
TI  - Mascot file parsing and quantification (MFPaQ), a new software to parse,
      validate, and quantify proteomics data generated by ICAT and SILAC mass
      spectrometric analyses: application to the proteomics study of membrane proteins
      from primary human endothelial cells.
AB  - Proteomics strategies based on nanoflow (nano-) LC-MS/MS allow the identification
      of hundreds to thousands of proteins in complex mixtures. When combined with
      protein isotopic labeling, quantitative comparison of the proteome from different
      samples can be achieved using these approaches. However, bioinformatics analysis
      of the data remains a bottleneck in large scale quantitative proteomics studies.
      Here we present a new software named Mascot File Parsing and Quantification
      (MFPaQ) that easily processes the results of the Mascot search engine and
      performs protein quantification in the case of isotopic labeling experiments
      using either the ICAT or SILAC (stable isotope labeling with amino acids in cell
      culture) method. This new tool provides a convenient interface to retrieve Mascot
      protein lists; sort them according to Mascot scoring or to user-defined criteria
      based on the number, the score, and the rank of identified peptides; and to
      validate the results. Moreover the software extracts quantitative data from raw
      files obtained by nano-LC-MS/MS, calculates peptide ratios, and generates a non
      redundant list of proteins identified in a multisearch experiment with their
      calculated averaged and normalized ratio. Here we apply this software to the
      proteomics analysis of membrane proteins from primary human endothelial cells
      (ECs), a cell type involved in many physiological and pathological processes
      including chronic inflammatory diseases such as rheumatoid arthritis. We analyzed
      the EC membrane proteome and set up methods for quantitative analysis of this
      proteome by ICAT labeling. EC microsomal proteins were fractionated and analyzed
      by nano-LC-MS/MS, and database searches were performed with Mascot. Data
      validation and clustering of proteins were performed with MFPaQ, which allowed
      identification of more than 600 unique proteins. The software was also
      successfully used in a quantitative differential proteomics analysis of the EC
      membrane proteome after stimulation with a combination of proinflammatory
      mediators (tumor necrosis factor-alpha, interferon-gamma, and lymphotoxin
      alpha/beta) that resulted in the identification of a full spectrum of EC membrane
      proteins regulated by inflammation.

PMID- 17533221
TI  - The implications of proteolytic background for shotgun proteomics.
AB  - The analysis by liquid chromatography coupled to tandem mass spectrometry of
      complex peptide mixtures, generated by proteolysis of protein samples, is the
      main proteomics method used today. The approach is based on the assumption that
      each protein present in a sample reproducibly and predictably generates a
      relatively small number of peptides that can be identified by mass spectrometry.
      In this study this assumption was examined by a targeted peptide sequencing
      strategy using inclusion lists to trigger peptide fragmentation attempts. It was
      found that the number of peptides observed from a single protein is at least one
      order of magnitude greater than previously assumed. This unexpected complexity of
      proteomics samples implies substantial technical challenges, explains some
      perplexing results in the proteomics literature, and prompts the need for
      developing alternative experimental strategies for the rapid and comprehensive
      analysis of proteomes.

PMID- 17533222
TI  - Comparative evaluation of tandem MS search algorithms using a target-decoy search
      strategy.
AB  - Peptide identification of tandem mass spectra by a variety of available search
      algorithms forms the foundation for much of modern day mass spectrometry-based
      proteomics. Despite the critical importance of proper evaluation and
      interpretation of the results generated by these algorithms there is still little
      consistency in their application or understanding of their similarities and
      differences. A survey was conducted of four tandem mass spectrometry peptide
      identification search algorithms, including Mascot, Open Mass Spectrometry Search
      Algorithm, Sequest, and X! Tandem. The same input data, search parameters, and
      sequence library were used for the searches. Comparisons were based on commonly
      used scoring methodologies for each algorithm and on the results of a target
      decoy approach to sequence library searching. The results indicated that there is
      little difference in the output of the algorithms so long as consistent scoring
      procedures are applied. The results showed that some commonly used scoring
      procedures may lead to excessive false discovery rates. Finally an alternative
      method for the determination of an optimal cutoff threshold is proposed.

PMID- 17533223
TI  - Influence of HDL-cholesterol-elevating drugs on the in vitro activity of the HDL
      receptor SR-BI.
AB  - Treatment of atherosclerotic disease often focuses on reducing plasma LDL
      cholesterol or increasing plasma HDL-cholesterol. We examined in vitro the
      effects on HDL receptor [scavenger receptor class B type I (SR-BI)] activity of
      three classes of clinical and experimental plasma HDL-cholesterol-elevating
      compounds: niacin, fibrates, and HDL376. Fenofibrate (FF) and HDL376 were potent
      (IC(50) approximately 1 microM), direct inhibitors of SR-BI-mediated lipid
      transport in cells and in liposomes reconstituted with purified SR-BI. FF, a
      prodrug, was a more potent inhibitor of SR-BI than an activator of peroxisome
      proliferator-activated receptor alpha, a target of its active fenofibric acid
      (FFA) derivative. Nevertheless, FFA, four other fibrates (clofibrate,
      gemfibrozil, ciprofibrate, and bezafibrate), and niacin had little, if any,
      effect on SR-BI, suggesting that they do not directly target SR-BI in vivo.
      However, similarities of HDL376 treatment and SR-BI gene knockout on HDL
      metabolism in vivo (increased HDL-cholesterol and HDL particle sizes) and
      structure-activity relationship analysis suggest that SR-BI may be a target of
      HDL376 in vivo. HDL376 and other inhibitors may help elucidate SR-BI function in
      diverse mammalian models and determine the therapeutic potential of SR-BI
      directed pharmaceuticals.

PMID- 17533322
TI  - Fractionated stereotactic radiotherapy for pediatric patients with
      retinoblastoma.
AB  - In this report we discuss the application of a modified Gill-Thomas-Cosman (GTC)
      relocatable head frame to enable fractionated stereotactic radiotherapy (SRT) of
      infants under anesthesia. This system has been used to treat two infants, ages 12
      and 18 months for bilateral retinoblastoma on a Varian 6/100 linear accelerator.
      The GTC head frame was used to reproduceably position and treat the orbits of
      these children to between 2520 and 3960 cGy in 180 cGy fractions. A standard head
      and neck tray, with accompanying thermoplastic mask, was adapted to mount to the
      head frame to enable these treatments. We found the maximum average deviation in
      the repeat fixations, as compared with the initial fitting data, to be +/- 2 mm.
      The overall average difference and standard deviation in measurement was 0.47 +/-
      0.63 mm for the first case, and 0.19 +/- 0.94 mm for the second case with a
      combined average of 0.35 +/- 0.79 mm overall from a total of 381 point
      measurements. The stereotactic treatment plan (Radionics) incorporated a single
      isocenter for each orbit and 3-4 arcs per isocenter. Inter-comparisons have been
      made between this technique and a standard lateral field technique, designed
      using the SRS planning system. Dose-volume histograms and corresponding normal
      tissue complication probabilities (NTCP) based on pediatric bone growth
      inhibition have been calculated for each method for the orbital bone areas. We
      have found that the NTCP is reduced from 95-100% in the standard treatment method
      to 16% or less with SRT. Use of the modified head frame provides excellent setup
      reproducibility, facilitates access to patients for anesthesia and reduces the
      chances of a poor cosmetic result in these growing children.

PMID- 17533323
TI  - Verifying monitor unit calculations for tangential breast fields.
AB  - An essential component of quality assurance in radiation therapy is verifying the
      accuracy of monitor unit calculations. Differences between between sophisticated
      algorithms using 2.5D or 3D calculations and simpler Monitor unit check
      algorithms assuming a flat water phantom must be expected. For many anatomical
      sites such differences are small and of little or no consequence in the context
      of monitor unit verification. However, for tangential breast fields the
      discrepancies are considerably larger than those that would generally be
      considered acceptable. A simple model to reconcile the differences between
      sophisticated and simple algorithms is presented based on replacing the breast
      contour with a triangular or elliptical contour and using this to estimate an
      equivalent rectangle providing equivalent scatter to the prescription point. The
      elliptical approximation reconciles the observed differences in calculated
      monitor units. The analysis we present can assist the treatment planning
      physicist in selecting a method and tolerance window for verifying monitor unit
      calculations for tangential breast fields.

PMID- 17533324
TI  - Performance and characteristics of an IR localizing system for radiation therapy.
AB  - We report the development of a new system for interactive patient posture,
      position and respiratory control during radiation therapy treatment. The system
      consists of an infrared camera, retro-reflective markers and dedicated software
      that makes it practical to use in the clinic. The system is designed to be used
      with multiple retro-reflective markers to monitor not only position, but also the
      posture of the patient in real time. Specific features of the system include: 1.
      The system reports an absolute misalignment at several points on a patients, and
      also provides feedbacks on any necessary adjustments in terms of site specific
      set-up parameters, such as focus to surface distance (PIN), superior and inferior
      alignment, chest-wall angle, etc. 2. The system is based on the set of predefined
      templates containing number and position of control points and feedback
      parameters developed for different treatment sites. 3. A "virtual portal vision"
      procedure is developed to project organ contours in the beams-eye-view (BEV)
      based on the marker locations obtained in real time and compare them with
      digitally reconstructed radiographs (DRRs) from CT simulation. Assuming good
      correlation between external markers and internal anatomy, the system offers the
      possibility of mimicking a verification procedure without taking port-films,
      which can potentially reduce the setup time. In this paper, we concentrate on
      system properties and performance, while initial applications on a number of
      clinical sites is ongoing. Accuracy and precision of this system are evaluated in
      the context of breast/chest treatments using rigid phantoms. The system has an
      intrinsic uncertainty of +/- 1 mm; and when two systems in different rooms (CT
      and treatment room) are used for correlating positional information, the
      uncertainty is less than 2 mm.

PMID- 17533325
TI  - Accuracy of rapid radiographic film calibration for intensity-modulated radiation
      therapy verification.
AB  - A single calibration film method was evaluated for use with intensity-modulated
      radiation therapy film quality assurance measurements. The single-film method has
      the potential advantages of exposure simplicity, less media consumption, and
      improved processor quality control. Potential disadvantages include cross
      contamination of film exposure, implementation effort to document delivered dose,
      and added complication of film response analysis. Film response differences were
      measured between standard and single-film calibration methods. Additional
      measurements were performed to help trace causes for the observed discrepancies.
      Kodak X-OmatV (XV) film was found to have greater response variability than
      extended dose range (EDR) film. We found it advisable for XV film to relate the
      film response calibration for the single-film method to a user-defined optimal
      calibration geometry. Using a single calibration film exposed at the time of
      experiment, the total uncertainty of film response was estimated to be <2% (1%)
      for XV (EDR) film at 50 (100) cGy and higher, respectively.

PMID- 17533326
TI  - Extracranial doses in stereotactic and conventional radiotherapy for pituitary
      adenomas.
AB  - The purpose of this study is to determine the extracranial dose in patients
      treated for pituitary adenoma with conventional and stereotactic radiotherapy
      (SRT). Twelve patients receiving treatment with radiation for pituitary adenoma
      were selected. Six patients underwent SRT, and six patients underwent
      conventional radiotherapy. Extracranial doses were measured with pre-irradiation
      annealed lithium fluoride thermoluminscent dosimetry (TLD) chips. The chips were
      wrapped and placed on the patients' skin, over each eyelid, the thyroid, chest,
      and scrotum for males and over the suprapubic region for females. Postradiation
      annealing was done, and the TLDs were read in a TLD reader system. The results
      were analyzed using the Wilcoxon matched-pairs signed rank test by SPSS, version
      6.01. The doses to the thyroid, center, and gonads were significantly higher
      (74.62 +/- 9.12 mrad, 65.42 +/- 9.35 mrad, and 58.42 +/- 5.36 mrad, respectively)
      in patients receiving SRT than in conventional radiotherapy portals (69.45 +/-
      21.19 mrad, 38.33 +/- 19.44 mrad, and 31.41 +/- 18.25 mrad). But the average
      doses to the right eye (84.84 +/- 8.80 mrad) and to the left eye (85.68 +/- 5.82
      mrad) in the stereotactic group were less when compared with the patients treated
      with conventional radiotherapy, who received 127.5 +/- 37.90 mrad and 117.29 +/-
      34.01 mrad, respectively. In conclusion, SRT is definitely superior to
      conventional radiotherapy as far as dose to the surrounding normal structures is
      concerned. The higher extracranial doses in SRT seem to be within the acceptable
      range; however, the clinical significance of this is still unclear and needs
      longer followup.

PMID- 17533327
TI  - PTV margin for dose escalated radiation therapy of prostate cancer with daily on
      line realignment using internal fiducial markers: Monte Carlo approach and dose
      population histogram (DPH) analysis.
AB  - Using internal fiducial markers and electronic portal imaging (EPID) to realign
      patients has been shown to significantly reduce positioning uncertainties in
      prostate radiation treatment. This creates the possibility of decreasing the
      planning target volume (PTV) margin added on the clinical target volume (CTV),
      which in turn may allow for dose escalation. We compared the outcome of two
      plans: 70Gy/35fx, 10 mm PTV margin without patient realignment (Reference Plan)
      vs. 78Gy/39fx, 5 mm PTV margin with patient realignment (Escalated Plan). Four
      field-oblique (gantry angles 35 degrees, 90 degrees, 270 degrees, 176 degrees,
      325 degrees) beam arrangement was used. Monte Carlo code was used to simulate the
      daily organ motion. Dose to each organ was calculated. Tumour control probability
      (TCP) and the effective dose to critical organ (Deff) were calculated using the
      biologically normalized dose-volume histograms. By comparing the biological
      factors, we found that the prescription dose can be escalated to 78Gy/39fx with a
      5 mm PTV margin when using internal fiducial markers and EPID. Based on the
      available dose-response data for intermediate risk prostate patients, this will
      result in a 20% increase of local control and significantly reduced rectal
      complications provided that less serial dose-volume behaviour of rectum is
      proven.

PMID- 17533328
TI  - Applicator volume elimination methods and their influence on DVH analysis of HDR
      prostate implants.
AB  - In CT anatomy-based inverse treatment planning of interstitial high-dose rate
      (HDR) brachytherapy planning, the planning target volume (PTV) delineated by the
      radiation oncologist includes the applicator volume. The applicator volume can be
      eliminated with the help of two methods: one based on Boolean operations and the
      other using the erasing option of the application software. Both methods are
      compared, and the results are discussed. Elimination of the applicator volume
      results in the proper estimation of the PTV and the exclusion of the clinically
      insignificant hot volume from the PTV in the dose-volume histogram (DVH)
      analysis. Five cases of prostate cancer are considered for analysis. The PTV,
      applicator volume, maximum, mean, modal, and minimum dose, and the percentage
      volume of the PTV structure receiving the percent dose for both cases, that is,
      with and without applicator volume, are tabulated and analyzed. The elimination
      of the applicator volume results in the proper volume estimation of the PTV
      structure and leads to better DVH analysis of interstitial HDR prostate implants.
      The procedure would have little relevance in routine planning but improves dose
      reporting. It is too early to conclude its clinical significance or
      insignificance.

PMID- 17533329
TI  - Analysis of the sources of uncertainty for EDR2 film-based IMRT quality
      assurance.
AB  - In our institution, patient specific quality assurance (QA) for intensity
      modulated radiation therapy (IMRT) is usually performed by measuring the dose to
      a point using an ion chamber and by measuring the dose to a plane using film. In
      order to perform absolute dose comparison measurements using film, an accurate
      calibration curve should be used. In this paper, we investigated the film
      response curve uncertainty factors including film batch differences, film
      processor temperature effect, film digitization, and treatment unit. In addition,
      we reviewed fifty patient-specific IMRT QA procedures performed in our
      institution in order to quantify the sources of error in film based dosimetry.
      Our study showed that the EDR2 film dosimetry can be done with less than 3%
      uncertainty. The EDR2 film response was not affected by the choice of treatment
      unit provided the nominal energy was the same. This investigation of the
      different sources of uncertainties in the film calibration procedure can provide
      a better understanding of the film based dosimetry and improve quality control
      for IMRT QA.

PMID- 17533330
TI  - SWIMRT: a graphical user interface using sliding window algorithm to construct a
      fluence map machine file.
AB  - A custom-made computer program, SWIMRT, to construct "multileaf collimator (MLC)
      machine" file for intensity-modulated radiotherapy (IMRT) fluence maps was
      developed using MATLAB and the sliding window algorithm. The user can either
      import a fluence map with a graphical file format created by an external
      treatment-planning system such as Pinnacle3 or create his or her own fluence map
      using the matrix editor in the program. Through comprehensive calibrations of the
      dose and the dimension of the imported fluence field, the user can use associated
      image-processing tools such as field resizing and edge trimming to modify the
      imported map. When the processed fluence map is suitable, a "MLC machine" file is
      generated for our Varian 21 EX linear accelerator with a 120-leaf Millennium MLC.
      This machine file is transferred to the MLC console of the LINAC to control the
      continuous motions of the leaves during beam irradiation. An IMRT field is then
      irradiated with the 2D intensity profiles, and the irradiated profiles are
      compared to the imported or modified fluence map. This program was verified and
      tested using film dosimetry to address the following uncertainties: (1) the
      mechanical limitation due to the leaf width and maximum traveling speed, and (2)
      the dosimetric limitation due to the leaf leakage/transmission and penumbra
      effect. Because the fluence map can be edited, resized, and processed according
      to the requirement of a study, SWIMRT is essential in studying and investigating
      the IMRT technique using the sliding window algorithm. Using this program, future
      work on the algorithm may include redistributing the time space between segmental
      fields to enhance the fluence resolution, and readjusting the timing of each leaf
      during delivery to avoid small fields. Possible clinical utilities and examples
      for SWIMRT are given in this paper.

PMID- 17533331
TI  - The dosimetric effect of inhomogeneity correction in dynamic conformal arc
      stereotactic body radiation therapy for lung tumors.
AB  - For patients treated with lung stereotactic body radiation therapy (SBRT) using
      dynamic conformal arcs, the influence of inhomogeneity correction (IC) on normal
      tissue and tumor dosimetry was studied. For the same numbers of monitor units,
      the planning target volume equivalent uniform doses calculated without path
      length IC were lower than those calculated with IC (mean difference 18%, range 1
      34%; p < 0.0001). Normal lung dose differences were of the same magnitude in
      opposite direction. In reports of SBRT, it will be helpful to maintain clear
      communication about the type of IC used to avoid future uncertainties about true
      normal tissue tolerance and tumor dose-response relationships.

PMID- 17533337
TI  - Use of a multileaf collimator to increase the field width achievable with a
      dynamic wedge.
AB  - A method is proposed for generating dynamic wedges spanning the entire field
      width, defined as the collimator opening in the wedged direction, without changes
      to existing hardware. The technique approximates the fluence pattern of a dynamic
      wedge by sequentially closing the leaves of a 120-leaf multileaf collimator
      (MLC). Closure times for the individual leaves were derived by extending the
      segmented treatment table of the dynamic wedge provided by the manufacturer of
      the linear accelerator. Using film dosimetry, beam properties of MLC wedges were
      compared to those of conventional dynamic and mechanical wedges. Profiles and
      isodose lines of the MLC wedge were almost identical to those of the dynamic
      wedge, and differed only modestly from the mechanical counterparts. Dose
      inhomogeneity due to the individually closing leaves was not significant. The
      high-dose region at the junction between opposing MLC leaves, unavoidable when
      the field length (i.e., the opening of the collimator in the nonwedged direction)
      exceeds the maximum leaf extension of 15 cm, was feathered by moving leaf pairs
      after their closure for the remainder of the irradiation time. Combining the MLC
      wedge with a regular dynamic wedge to reduce the line of high dose under the leaf
      junction is under consideration.

PMID- 17533338
TI  - Estimation of patient organ doses from CT examinations in Tanzania.
AB  - Although the use of computed tomography (CT) in medical diagnosis delivers
      relatively higher radiation doses to patients than other radiological procedures,
      lack of optimized protocols could be an additional source of increased dose in
      developing countries. The aim of this study was to determine the magnitude of
      radiation doses received by selected radiosensitive organs of patients from CT
      examinations. The study was further carried out in order to assess the influence
      of existing CT scanning protocols on patient organ doses. In order to achieve
      these objectives, patient organ doses from five common CT examinations were
      obtained from eight hospitals in Tanzania. The patient organ doses were estimated
      using measurements of CTDI, exposure-related parameters and the NRPB conversion
      factors. Large variation of mean organ doses among hospitals was observed for
      similar CT examinations. These variations were largely originated from different
      CT scanning protocols employed in different hospitals and scanner type. The mean
      organ doses in this study for the lens of the eyes (for head), thyroid (for
      chest), breast (for chest), stomach (for abdomen), and ovary (for pelvis), were
      63.9 mGy, 12.3 mGy, 26.1 mGy, 35.6 mGy, and 24.0 mGy, respectively. These values
      were mostly comparable and slightly higher than the values of organ doses
      reported from literature for the UK, Japan, Germany, Norway and the Netherlands.
      It was concluded that patient organ doses could substantially minimized through
      careful selection of scanning parameters based on clinical indications of study,
      patient size, and body region being examined. Additional dose reduction to
      superficial organs would require the use of shielding materials.

PMID- 17533339
TI  - Out-of-field dosimetry measurements for a helical tomotherapy system.
AB  - Helical tomotherapy is a rotational delivery technique that uses intensity
      modulated fan beams to deliver highly conformal intensity-modulated radiation
      therapy (IMRT). The beam-on time needed to deliver a given prescribed dose can be
      up to 15 times longer than that needed using conventional treatment delivery. As
      such, there is concern that this delivery technique has the potential to increase
      the whole body dose due to increased leakage. The purpose of this work is to
      directly measure out-of-field doses for a clinical tomotherapy system. Peripheral
      doses were measured in-phantom using static fields and rotational intensity
      modulated delivery. In-air scatter and leakage doses were also measured at
      multiple locations around the treatment room. At 20 cm, the tomotherapy
      peripheral dose dropped to 0.4% of the prescribed dose. Leakage accounted for 94%
      of the in-air dose at distances greater than 60 cm from the machine's isocenter.
      The largest measured dose equivalent rate was 1 x 10(-4) Sv/s in the plane of
      gantry rotation due to head leakage and primary beam transmission through the
      system's beam stopper. The dose equivalent rate dropped to 1 x 10(-6) Sv/s at the
      end of the treatment couch. Even though helical tomotherapy treatment delivery
      requires beam-on times that are 5 to 15 times longer than those used by
      conventional accelerators, the delivery system was designed to maximize shielding
      for radiation leakage. As such, the peripheral doses are equal to or less than
      the published peripheral doses for IMRT delivery on other linear accelerators. In
      addition, the shielding requirements are also similar to conventional linear
      accelerators.

PMID- 17533340
TI  - Long term stability of a 50 kV X-ray unit for stereotactic irradiation.
AB  - A low-energy (50 kV) X-ray tube used for the stereotactic irradiation of
      intracranial lesions has been in use since 1999. The unit is calibrated prior to
      every procedure and during periodic quality assurance (QA) tests. The unit uses
      an internal and an external scintillation detector to monitor dose as well as a
      conventional timer. The records of these calibrations were reviewed to see
      whether a change in the output had occurred over that period. Using time as the
      reference, it was found that both the internal radiation monitor (IRM) and the
      beam output, determined with a parallel plate ionization chamber, dropped by
      variable amounts over the given period. The beam output dropped significantly
      more than the IRM, while the external radiation monitor (ERM) showed no
      significant deviation from its initial value. The beam output dropped to about
      90% of its initial value after about 200 days but remained relatively constant
      thereafter. The IRM dropped steadily to about 96% to 97% of its initial value at
      1000 days, but recovered to about 98% after that. Calibration prior to each
      procedure is strongly recommended.

PMID- 17533341
TI  - Investigating treatment dose error due to beam attenuation by a carbon fiber
      tabletop.
AB  - Carbon fiber is commonly used in radiation therapy for treatment tabletops and
      various immobilization and support devices, partially because it is generally
      perceived to be almost radiotransparent to high-energy photons. To avoid exposure
      to normal tissue during modern radiation therapy, one must deliver the radiation
      from all gantry angles; hence, beams often transit the couch proximal to the
      patient. The effects of the beam attenuation by the support structure of the
      couch are often neglected in the planning process. In this study, we investigate
      the attenuation of 6-MV and 18-MV photon beams by a Medtec (Orange City, IA)
      carbon fiber couch. We have determined that neglecting the attenuation of oblique
      treatment fields by the carbon fiber couch can result in localized dose reduction
      from 4% to 16%, depending on energy, field size, and geometry. Further, we
      investigate the ability of a commercial treatment-planning system (Theraplan Plus
      v3.8) to account for the attenuation by the treatment couch. Results show that
      incorporating the carbon fiber couch in the patient model reduces the dose error
      to less than 2%. The variation in dose reduction as a function of longitudinal
      couch position was also measured. In the triangular strut region of the couch,
      the attenuation varied +/- 0.5% following the periodic nature of the support
      structure. Based on these findings, we propose the routine incorporation of the
      treatment tabletop into patient treatment planning dose calculations.

PMID- 17533342
TI  - Study of the influence of phantom material and size on the calibration of
      ionization chambers in terms of absorbed dose to water.
AB  - In the International Atomic Energy Agency's (IAEA) code of practice (TRS 398) and
      the American Association of Physicists in Medicine's dosimetry protocol (TG-51),
      full-scatter water phantoms are recommended for the determination of the absorbed
      dose for both photon and electron beams and, consequently, for the calibration of
      the user's ionization chambers. This procedure is applied in the Secondary
      Standard Dosimetry Laboratory, where the calibration is performed on a 60Co gamma
      beam, in comparison with reference chambers whose absorbed dose-to-water
      calibration coefficients, ND,w, are known. In this work, we present the results
      of the calibration of 10 Farmer-like ionization chambers calibrated in three
      water phantoms (sizes 20 x 20 x 15 cm3, 30 x 30 x 30 cm3, and 35 x 35 x 37 cm3)
      and two plastic phantoms (size 20 x 20 x 20 cm3) polymethyl methacrlyate (PMMA)
      and polystyrene). Calibrations are performed by the substitution method using an
      ionization chamber whose ND,w has been supplied by the IAEA's reference
      laboratory. It is shown that the results, expressed as the percentage ratio of
      the calibration coefficient in a given phantom to that of the standard IAEA
      phantom, is less than 0.35% for all investigated chambers, and that the standard
      deviation of the mean of the ND,w calibration coefficients determined in all five
      phantoms is less than 0.06%, except for one nylon-walled ionization chamber,
      where the observed 0.34% value could be explained by the hygroscopic properties
      of nylon. Furthermore, a chamber-to-chamber dependence of the calibration
      coefficient has been shown to vary by up to 2.8%. These results emphasize that
      the phantom dimensions and its material are not sensitive criteria for the
      calibration of cylindrical ionization chambers in terms of absorbed dose to
      water. The results also show that generic calibration coefficients could not be
      considered for a given type of chamber.

PMID- 17533343
TI  - Comparison of measured and computed portal dose for IMRT treatment.
AB  - A new 2D array Seven 29T model (PTW, Freiburg), equipped with 729 vented plane
      parallel ion chambers, projected for pretreatment verification of radiotherapy
      plans, was used as a detector for the transmitted or portal dose measurements
      below a Rando phantom. The dosimetric qualities of the 2D array make it
      attractive for measuring transmitted dose maps from step-and-shoot intensity
      modulated radiotherapy (IMRT). It is well known that for step-and-shoot IMRT
      beams that use a small number of monitor units (MUs) per sequence, the early and
      recent electronic portal imaging devices (EPIDs) present a different response at
      X-ray start-up that affects the accuracy of the measured transmitted dose. The
      comparison of portal doses measured to those calculated by a commercial treatment
      planning system (TPS) can verify correct dose delivery during treatment. This
      direct validation was tested by irradiating a simulated head tumor in a Rando
      anthropomorphic phantom by step-and-shoot IMRT beams. The absolute transmitted
      doses on a plane orthogonal to the beam central axis below the phantom were
      measured by the 2D array calibrated in terms of dose to water and compared with
      the computed portal dose extracted by custom software. In a previous paper, the
      comparison between the IMRT portal doses, computed by a commercial TPS and
      measured by a linear array that supplied a 1 mm spatial dose resolution, was
      carried out. The gamma-index analysis supplied an agreement of more than 95% of
      the dose point with acceptance criteria, in terms of dose difference, DeltaDmax,
      and distance agreement, deltadmax, equal to 4% and 4 mm, respectively. In this
      paper, we verify the possible use of the PTW 2D array for measurements of the
      transmitted doses during several fractions of head and neck tumor radiotherapy.
      There are two advantages in the use of this 2D array as a portal dose device for
      the IMRT quality assurance program: first is the ability to perform absolute dose
      comparisons for hundreds of measurement positions to verify the correct dose
      delivery in several fractions of the therapy; second is the efficiency in time to
      detect these kinds of dose distributions within the field of view area of the CT
      scanner.

PMID- 17533345
TI  - Dose modification factors for 192Ir high-dose-rate irradiation using Monte Carlo
      simulation.
AB  - A recently introduced brachytherapy system for partial breast irradiation,
      MammoSite, consists of a balloon applicator filled with contrast solution and a
      catheter for insertion of an 192Ir high-dose-rate (HDR) source. In using this
      system, the treatment dose is typically prescribed to be delivered 1 cm from the
      balloon's surface. Most treatment-planning systems currently in use for
      brachytherapy procedures use water-based dosimetry with no correction for
      heterogeneity. Therefore, these systems assume that full scatter exists
      regardless of the amount of tissue beyond the prescription line. This assumption
      might not be a reasonable one, especially when the tissue beyond the prescription
      line is thin. In such a case, the resulting limited scatter could cause an
      underdose to be delivered along the prescription line. We used Monte Carlo
      simulations to investigate how the thickness of the tissue between the surface of
      the balloon and the skin or lung affected the treatment dose delivery.
      Calculations were based on a spherical water phantom with a diameter of 30 cm and
      balloons with diameters of 4 cm, 5 cm, and 6 cm. The dose modification factor is
      defined as the ratio of the dose rate at the typical prescription distance of 1
      cm from the balloon's surface with full scatter obtained using the water phantom
      to the dose rate with a finite tissue thickness (from 0 cm to 10 cm) beyond the
      prescription line. The dose modification factor was found to be dependent on the
      balloon diameter and was 1.098 for the 4-cm balloon and 1.132 for the 6-cm
      balloon with no tissue beyond the prescription distance at the breast-skin
      interface. The dose modification factor at the breast-lung interface was 1.067
      for the 4-cm balloon and 1.096 for the 6-cm balloon. Even 5 cm of tissue beyond
      the prescription distance could not result in full scatter. Thus, we found that
      considering the effect of diminished scatter is important to accurate dosimetry.
      Not accounting for the dose modification factor may result in delivering a lower
      dose than is prescribed.

PMID- 17533348
TI  - Evaluation of dosimetric effect of leaf position in a radiation field of an 80
      leaf multileaf collimator fitted to the LINAC head as tertiary collimator.
AB  - This study evaluates changes in the dosimetric characteristics of a Varian
      Millennium 80-leaf multileaf collimator (MLC) in a radiation field. In this
      study, dose rate, scatter factor, percentage depth dose, surface dose and dose in
      the buildup region, beam profile, flatness and symmetry, and penumbra width
      measurements were made for 6-MV and 15-MV photon beams. Analysis of widths
      between 50% dose levels of the beam profiles to reflect the field size at the
      level of profile measurement shows a significant difference between the fields
      defined by MLC and/or jaws and MLC (zero gap) and the fields defined by jaws
      only. The position of the MLC leaves in the radiation field also significantly
      affects scatter factors. A new relationship has, therefore, been established
      between the scatter factors and the position of the MLC, which will indeed be
      useful in the dose calculation for irregular fields. Penumbra widths increase
      with field size and were higher for fields defined by jaws and/or MLC than jaws
      and MLC (zero gap) by 1.5 mm to 4.2 mm and 3.8 mm to 5.0 mm, for 6-MV, and 1.5 mm
      to 2.4 mm and 3.0 mm to 5.6 mm, for 15-MV, at 20% to 80% and 10% to 90% levels,
      respectively. The surface dose and the dose in the buildup region were smaller
      for fields defined by jaws and MLC (zero gap) than the fields defined by jaws
      and/or MLC for both photon energies. No significant differences were found in
      percentage depth dose beyond dmax, beam profiles above 80% dose level, and
      flatness and symmetry for both energies. The results of this study suggest that
      while one collects linear accelerator beam data with a MLC, the effects of the
      positions of the MLC leaves play an important role in dosimetric characteristics
      of 3D conformal radiation therapy as well as intensity-modulated radiotherapy.

PMID- 17533350
TI  - Measurement of the interplay effect in lung IMRT treatment using EDR2 films.
AB  - Intra-fraction organ motion during the dynamic delivery of IMRT treatment of lung
      tumors may cause unexpected hot/cold spots even within the target volume, due to
      the interplay effect between tumor motion and multi-leaf collimator (MLC) leaf
      motion. In the past, this has been investigated through theoretical analysis,
      computer simulation, and experimental measurement using an ionization chamber
      dosimeter. In the work presented here, the interplay effect was studied
      experimentally in 2D, using Kodak EDR2 films. A five-field lung IMRT plan was
      delivered to a solid water phantom with embedded film. The phantom was placed on
      a motor-driven platform with a sinusoidal motion to simulate the respiration
      induced tumor motion. The delivery of each field began at one of eight equally
      spaced initial breathing phases. The dose distribution for each treatment
      fraction was estimated by combining the dose distributions for all fields with
      randomly sampled initial breathing phases. The dose variation caused by the
      interplay effect was estimated by looking at the dose values from 1000 trials of
      30 fractions. It was found that, on a day-to-day basis, the standard deviation of
      the dose to a given pixel in the high dose region could be as high as 2-3% due to
      the motion interplay effect. After thirty fractions, the standard deviation in
      the dose to each pixel is reduced to about 0.3-0.5%. However, compared to the
      static delivery, the dose distribution from a thirty-fraction case in the
      presence of motion shows some under-dosing in the region of interest. Our results
      indicate that the interplay effect is of no significant consequence to tumor dose
      coverage in lung IMRT delivery over the entire course of a thirty-fraction
      treatment.

PMID- 17533351
TI  - Effect of contrast enhanced CT scans on heterogeneity corrected dose computations
      in the lung.
AB  - The aim of this study was to investigate and, if possible, compensate for the
      effect of intravenous contrast-enhanced CT scans on the treatment planning dose
      distributions for lung patients. The contrast and noncontrast CT scans of 3
      patients were registered, and the effect of contrast on the Hounsfield units (HU)
      was assessed. The effect of contrast was then simulated in the CT scans of 18
      patients receiving radiotherapy of the lung by modification of the CT numbers for
      relevant sections of noncontrast-enhanced CT scans. All treatment planning was
      performed on the Pinnacle3 planning system. The dose distributions computed from
      simulated contrast CT scans were compared to the original dose distributions by
      comparison of the monitor units (MUs) for each beam in the treatment plan
      required to deliver the prescribed dose to the isocenter as well as a comparison
      of the total MUs for each patient, a percentage change in required MUs being
      equivalent to a percentage change in the dose. A correction strategy to enable
      the use of contrast-enhanced CT scans in treatment planning was developed, and
      the feasibility of applying the strategy was investigated by calculating dose
      distributions for both the original and simulated contrast CT scans. A mean
      increase in the overall patient MUs of 1.0 +/- 0.8% was found, with a maximum
      increase of 3.3% when contrast was simulated on the original CT scans. The
      simulated contrast scans confirmed that the use of contrast-enhanced CT scans for
      routine treatment planning would result in a systematic change in the dose
      delivered to the isocenter. The devised correction strategy had no clinically
      relevant effect on the dose distribution for the original CT scans. The
      application of the correction strategy to the simulated contrast CT scans led to
      a reduction of the mean difference in the overall MUs to 0.1 +/- 0.2% compared to
      the original scan, demonstrating that the effect of contrast was eliminated with
      the correction strategy. This work has highlighted the problems associated with
      using contrast-enhanced CT scans in heterogeneity corrected dose computation.
      Contrast visible in the CT scan is transient and should not be accounted for in
      the treatment plan. A correction strategy has been developed that minimizes the
      effect of intravenous contrast while having no clinical effect on noncontrast CT
      scans. The correction strategy allows the use of contrast without detriment to
      the treatment plan.

PMID- 17533352
TI  - Treatments of exceptionally large prostate cancer patients with low-energy
      intensity-modulated photons.
AB  - An inverse planning technique was developed for large-sized prostate cancer
      patients treatments using 6-MV intensity modulated photon beams. Comparisons of
      the treatment plans between using 6-MV and 18-MV intensity modulated beams were
      carried out for a cohort of ten patient cases. The dependence of the plan quality
      on the beam energies was analyzed for these cases. We found that 6-MV produced
      equivalent plans as 18-MV for both targets and critical structures such as the
      rectum and the bladder. The differences in the integral dose and the mean dose to
      the normal tissue surrounding the target between 6- and 18-MV plans were found to
      be small in contrast to 3D conformal plans. This shows that the low entrance dose
      of the high energy photon beams is mostly compensated by the high exit dose for
      even exceptionally large-size patients. In conclusion, 6-MV intensity modulated
      beam is a feasible choice for treating large-sized prostate cancer patients
      provided proper inverse planning techniques are adopted.

PMID- 17533353
TI  - Mechanical and dose delivery accuracy evaluation in radiosurgery using polymer
      gels.
AB  - The polymer gel-Magnetic Resonance Imaging (MRI) dosimetry technique was employed
      to evaluate the mechanical and dose delivery accuracy in Leksell gamma knife
      stereotactic radiosurgery for the treatment of multiple targets. Two different
      polymer gel dosimeter formulations that have been reported in the literature were
      prepared in-house. A plan for the treatment of four brain metastases (targets)
      was generated. The plan involved the delivery of four, 8 mm collimator shots
      using different prescription isodose lines and different prescription doses for
      each target, keeping the maximum dose constant for all the targets. A sample of
      each gel formulation was irradiated using a custom made phantom with an
      experimental procedure capable of testing the increased nominal mechanical
      accuracy of stereotactic radiosurgery. The irradiated dosimeters were evaluated
      using a clinical 1.5 T Philips ACS NT MR imager. Result manipulation in 3-D
      allowed for the determination of the mechanical accuracy in the delivery of each
      shot through the comparison of measured versus planned shot center coordinates.
      Dose delivery accuracy was also evaluated by comparison of maximum dose values
      measured at the center of each shot as well as dose distribution measurements,
      with corresponding treatment planning calculations. Polymer gel dosimetry was
      found capable of verifying the complete chain of radiosurgery treatment in gamma
      knife applications involving the irradiation of multiple targets.

PMID- 17533354
TI  - In vivo prostate IMRT dosimetry with MOSFET detectors using brass buildup caps.
AB  - The feasibility of using dual bias metal oxide semiconductor field effect
      transistors (MOSFET) detectors with the new hemispherical brass build up cap for
      in vivo dose measurements in Prostate IMRT treatments was investigated and
      achieved. A general formalism with various correction factors taken into account
      to predict Dmax entrance skin dose for the IMRT fields with MOSFETS was developed
      and compared against predicted dose from the treatment planning system. We
      achieved an overall accuracy better than +/- 5 % on all measured fields for both
      6 MV and 10 MV beams when compared to predicted doses from Philips Pinnacle3 and
      CMS XiO treatment planning systems respectively. We also estimate the total
      uncertainty in estimation of MOSFET dose in the high sensitivity mode for IMRT
      therapy to be 4.6%.

PMID- 17533355
TI  - Diagnostic X-ray facilities as per quality control performances in Tanzania.
AB  - Without appropriate quality control (QC) and preventative maintenance (PM)
      measures for X-ray machines in place, the benefits of reduced dose to the patient
      and early diagnosis will not be realized. Quality control and PM also make it
      possible to unify X-ray-imaging practices in the country using international
      image quality guidelines. The impetus for the present work resulted from the
      concern that with the recent increase in the numbers of X-ray machines in
      Tanzania, but with limited technical support to maintain and operate them, can
      increase radiation risk to patients and lower diagnostic accuracy. The aim of
      this work is to report on the current status of diagnostic X-ray machines in
      Tanzania in order to produce the data needed to formulate QC and PM policies and
      strategies. These policies and strategies are needed to ensure that patients
      receive the lowest possible radiation risk and maximum health benefits from X-ray
      examinations. Four QC tests were performed on a total of 196 X-ray units.
      Accurate beam alignment and collimation were tested on 80 (41%) units, the timer
      accuracy was tested on 120 (61%) units, and a radiation leakage test was
      performed on 47(24%) units. Preventative maintenance tests were performed on all
      196 X-ray units. The results showed that of the units tested for QC, 59% failed
      the kilovoltage (kVp) test, 57% failed the timer accuracy test, 60% failed the
      beam alignment test, and 20% failed the radiation leakage test. Only 13% of the
      units passed the PM test: 53% of the units were defective, and 34% were out of
      order. As a result of the PM findings, the government has introduced a
      rehabilitation project to service X-ray units and replace nonoperational X-ray
      units. The new units have full support service contracts signed by their
      suppliers. As a result of the QC findings, X-ray maintenance retraining programs
      have been introduced.

PMID- 17533356
TI  - Initial evaluation of a four-dimensional computed tomography system using a
      programmable motor.
AB  - A dynamic lung tumor phantom was used to investigate the geometric reconstruction
      accuracy of a commercial four-dimensional computed tomography (4D-CT) system. A
      ball filled with resin, embedded in a cork cube, was placed on a moving platform.
      Various realistic antero-posterior (AP) motions were programmed to reproduce the
      respiratory motion of a lung tumor. Several three-dimensional (3D) CT and 4D-CT
      images of this moving object were acquired and compared using different
      acquisition parameters. Apparent volume and diameter of the ball were measured
      and compared to the real values. The position of two points (the AP limits of the
      ball) during the motion in the coordinate system of the CT scanner were also
      compared with the expected values. Volume error was shown to increase with object
      speed. However, although the volume error was associated with intraslice
      artifacts, it did not reflect large interslice inconstancies in object position
      and should not be used as an indicator of image accuracy. The 3D-CT gave a random
      position of the tumor along the phantom excursion; accuracy in the assessment of
      position by 4D-CT ranged from 0.4 mm to 2.6 mm during extreme phases of
      breathing. We used average projection (AVE) and maximum intensity projection
      (MIP) algorithms available on the commercial software to create internal target
      volumes (ITVs) by merging gross tumor volume (GTV) images at various respiratory
      phases. The ITVs were compared to a theoretical value computed from the
      programmed ball excursion. The ITVs created from the MIP algorithm were closer to
      the theoretical value (within 12%) than were those created from the AVE algorithm
      (within 40%).

PMID- 17533357
TI  - An investigation of the potential of rapid prototyping technology for image
      guided surgery.
AB  - Image-guided surgery can be broken down into two broad categories: frame-based
      guidance and frameless guidance. In order to reduce both the invasive nature of
      stereotactic guidance and the cost in equipment and time, we have developed a new
      guidance technique based on rapid prototyping (RP) technology. This new system
      first builds a computer model of the patient anatomy and then fabricates a
      physical reference frame that provides a precise and unique fit to the patient
      anatomy. This frame incorporates a means of guiding the surgeon along a
      preplanned surgical trajectory. This process involves (1) obtaining a high
      resolution CT or MR scan, (2) building a computer model of the region of
      interest, (3) developing a surgical plan and physical guide, (4) designing a
      frame with a unique fit to the patient's anatomy with a physical linkage to the
      surgical guide, and (5) fabricating the frame using an RP unit. Software was
      developed to support these processes. To test the accuracy of this process, we
      first scanned and reproduced a plastic phantom fabricated to validate the
      system's ability to build an accurate virtual model. A target on the phantom was
      then identified, a surgical approach planned, a surgical guide designed, and the
      accuracy and precision of guiding a probe to that target were determined. Steps 1
      through 5 were also evaluated using a head phantom. The results show that the RP
      technology can replicate an object from CT scans with submillimeter resolution.
      The fabricated reference frames, when positioned on the surface of the phantom
      and used to guide a surgical probe, can position the probe tip with an accuracy
      of 1.7 mm at the probe tip. These results demonstrate that the RP technology can
      be used for the fabrication of customized positioning frames for use in image
      guided surgery.

PMID- 17533358
TI  - Observed inter-camera variability of clinically relevant performance
      characteristics for Siemens Symbia gamma cameras.
AB  - We conducted an evaluation of the intercamera (i.e., between cameras) variability
      in clinically relevant performance characteristics for Symbia gamma cameras
      (Siemens Medical Solutions, Malvern, PA) based on measurements made using nine
      separate systems. The significance of the observed intercamera variability was
      determined by comparing it to the intracamera (i.e., within a single camera)
      variability. Measurements of performance characteristics were based on the
      standards of the National Electrical Manufacturers Association and reports 6, 9,
      22, and 52 from the American Association of Physicists in Medicine. All
      measurements were performed using 99mTc (except 57Co used for extrinsic
      resolution) and low-energy, high-resolution collimation. Of the nine cameras,
      four have crystals 3/8 in. thick and five have crystals 5/8 in. thick. We
      evaluated intrinsic energy resolution, intrinsic and extrinsic spatial
      resolution, intrinsic integral and differential flood uniformity over the useful
      field-of-view, count rate at 20% count loss, planar sensitivity, single-photon
      emission computed tomography (SPECT) resolution, and SPECT integral uniformity.
      The intracamera variability was estimated by repeated measurements of the
      performance characteristics on a single system. The significance of the observed
      intercamera variability was evaluated using the two-tailed F distribution. The
      planar sensitivity of the gamma cameras tested was found be variable at the 99.8%
      confidence level for both the 3/8-in. and 5/8-in. crystal systems. The integral
      uniformity and energy resolution were found to be variable only for the 5/8-in.
      crystal systems at the 98% and 90% confidence level, respectively. All other
      performance characteristics tested exhibited no significant variability between
      camera systems. The measured variability reported here could perhaps be used to
      define nominal performance values of Symbia gamma cameras for planar and SPECT
      imaging.

PMID- 17533363
TI  - Alpha4 chain laminins are widely expressed in renal cell carcinomas and have a de
      adhesive function.
AB  - Laminin (Lm) alpha4 chain, a constituent of Lm-411 and Lm-421, is mainly
      localized to mesenchyme-derived tissues, and is suggested to have a role in
      formation and function of endothelium, transmigration of inflammatory cells
      through endothelium, and invasion of certain tumors. In this study, we evaluated
      the distribution of alpha4 chain Lms in 33 conventional (clear cell) renal cell
      carcinomas (RCCs) (31 primary tumors, two metastases), two papillary RCCs, and
      two oncocytomas by immunohistochemistry. In all tumors, immunoreactivity for Lm
      alpha4 chain was found in vasculature and stroma. Basement membranes were
      detected around tumor cell islets in 34/37 tumors. They showed immunoreactivity
      for Lm alpha4 chain in 28/34 cases. Northern blotting, inhibition of protein
      secretion with monensin, and immunoprecipitation combined with Western blotting
      showed that Caki-2, ACHN, and Caki-1 renal carcinoma cell lines produce alpha4
      chain Lms. In cell adhesion assay, recombinant human Lm-411 did not promote
      adhesion of renal carcinoma cells but inhibited adhesion to fibronectin (Fn). In
      cell migration assay, the cells migrated more on Lm-411 than on Fn. The results
      suggest that alpha4 chain Lms have a de-adhesive function and could thus play a
      role in detachment, migration and invasion of renal carcinoma cells in vivo.

PMID- 17533364
TI  - Identification of candidate genes involved in neuroblastoma progression by
      combining genomic and expression microarrays with survival data.
AB  - Identifying genes, whose expression is consistently altered by chromosomal gains
      or losses, is an important step in defining genes of biological relevance in a
      wide variety of tumour types. However, additional criteria are needed to
      discriminate further among the large number of candidate genes identified. This
      is particularly true for neuroblastoma, where multiple genomic copy number
      changes of proven prognostic value exist. We have used Affymetrix microarrays and
      a combination of fluorescent in situ hybridization and single nucleotide
      polymorphism (SNP) microarrays to establish expression profiles and delineate
      copy number alterations in 30 primary neuroblastomas. Correlation of microarray
      data with patient survival and analysis of expression within rodent neuroblastoma
      cell lines were then used to define further genes likely to be involved in the
      disease process. Using this approach, we identify >1000 genes within eight
      recurrent genomic alterations (loss of 1p, 3p, 4p, 10q and 11q, 2p gain, 17q
      gain, and the MYCN amplicon) whose expression is consistently altered by copy
      number change. Of these, 84 correlate with patient survival, with the minimal
      regions of 17q gain and 4p loss being enriched significantly for such genes.
      These include genes involved in RNA and DNA metabolism, and apoptosis.
      Orthologues of all but one of these genes on 17q are overexpressed in rodent
      neuroblastoma cell lines. A significant excess of SNPs whose copy number
      correlates with survival is also observed on proximal 4p in stage 4 tumours, and
      we find that deletion of 4p is associated with improved outcome in an extended
      cohort of tumours. These results define the major impact of genomic copy number
      alterations upon transcription within neuroblastoma, and highlight genes on
      distal 17q and proximal 4p for downstream analyses. They also suggest that
      integration of discriminators, such as survival and comparative gene expression,
      with microarray data may be useful in the identification of critical genes within
      regions of loss or gain in many human cancers.

PMID- 17533365
TI  - Epigenetic silencing of prostaglandin E receptor 2 (PTGER2) is associated with
      progression of neuroblastomas.
AB  - We previously identified a cluster of prostanoid receptor genes, prostaglandin D2
      receptor (PTGDR) and prostaglandin E receptor 2 (PTGER2), as possible targets for
      DNA methylation in advanced types of neuroblastoma (NB) using bacterial
      artificial chromosome array-based methylated CpG island amplification method.
      Among them, in this study, we found that PTGER2 was frequently silenced in NB
      cell lines, especially in those with MYCN amplification, through epigenetic
      mechanisms. In NB cell lines, DNA methylation pattern within a part of CpG island
      was inversely correlated with PTGER2 expression, and histone H3 and H4
      deacetylation and histone H3 lysine 9 methylation within the putative promoter
      region were more directly correlated with silencing of this gene. Methylation of
      PTGER2 was observed more frequently in advanced-type of primary NBs compared with
      early-stage tumors. Growth of NB cells lacking endogenous PTGER2 expression was
      inhibited by restoration of the gene product by transient and stable
      transfection. A PTGER2-selective agonist, butaprost, increased intracellular
      cyclic adenosine monophosphate (cAMP) level, inhibited cell growth and induced
      apoptosis of NB cells stably expressing exogenous PTGER2. 8-Bromo-cAMP also
      inhibited growth of NB cells lacking PTGER2 expression, but not cells expressing
      this gene. Taken together, it is suggested that NB cells may lose responsiveness
      to PTGER2-mediated growth inhibition/apoptosis through epigenetic silencing of
      PTGER2 and/or disruption of downstream cAMP-dependent pathway during the
      neuroblastomagenesis.

PMID- 17533366
TI  - Deletion of Tip30 leads to rapid immortalization of murine mammary epithelial
      cells and ductal hyperplasia in the mammary gland.
AB  - Transformation of mammary epithelial cells (MECs) from the normal to the
      neoplastic stage requires the dysregulation of tumor suppressor genes and proto
      oncogenes. Tip30 is a tumor suppressor that can inhibit estrogen receptor
      mediated transcription in MECs, but its role in MEC proliferation remains
      unknown. Here, we show that deleting the Tip30 gene leads to ductal hyperplasia
      in mouse mammary glands early in life and extensive mammary hyperplasia with age.
      Tip30(-/-) mammary glands transplanted into wild-type mammary fat pads also
      display mammary trees with extensive ductal hyperplasia. Strikingly, Tip30
      deletion promotes proliferation of primary MECs and results in rapid
      immortalization of MECs in vitro relative to wild-type cells. Gene array analysis
      identified significant increases in the expression of mammary epithelial growth
      factors Wisp2 and Igf-1 in Tip30(-/-) cells. Knockdown of either Wisp2 or Igf-1
      using short interfering RNA dramatically inhibited proliferation of Tip30(-/-)
      cells. Together, these results suggest that Tip30 is an intrinsic and negative
      regulator of MEC proliferation partly through the inhibition of Wisp2 and Igf-1
      expression, and its absence in the mammary gland may predispose MECs to
      neoplastic transformation.

PMID- 17533367
TI  - Evaluation of the 3p21.3 tumour-suppressor gene cluster.
AB  - Deletions of the 3p21.3 region are a frequent and early event in the formation of
      lung, breast, kidney and other cancers. Intense investigation of allelic losses
      and the discovery of overlapping homozygous deletions in lung and breast tumour
      cell lines have defined a minimal critical 120 kb deletion region containing
      eight genes and likely to harbor one or more tumour-suppressor genes (TSGs). The
      candidate genes are HYAL2, FUS1, Ras-associated factor 1 (RASSF1), BLU/ZMYND10,
      NPR2L, 101F6, PL6 and CACNA2D2. Recent research indicates that several of these
      genes can suppress the growth of lung and other tumour cells. Furthermore, some
      genes (RASSF1A and BLU/ZMYND10) are very frequently inactivated by non-classical
      mechanisms such as promoter hypermethylation resulting in loss of expression.
      These data indicate that the 120 kb critical deletion region at 3p21.3 may
      represent a TSG cluster with preferential inactivation of particular genes
      depending on tumour type. The eight genes within this region and their potential
      role in cancer will be the focus of this review.

PMID- 17533368
TI  - TRPV6 channel controls prostate cancer cell proliferation via Ca(2+)/NFAT
      dependent pathways.
AB  - The transient receptor potential channel, subfamily V, member 6 (TRPV6), is
      strongly expressed in advanced prostate cancer and significantly correlates with
      the Gleason >7 grading, being undetectable in healthy and benign prostate
      tissues. However, the role of TRPV6 as a highly Ca(2+)-selective channel in
      prostate carcinogenesis remains poorly understood. Here, we report that TRPV6 is
      directly involved in the control of prostate cancer cell (LNCaP cell line)
      proliferation by decreasing: (i) proliferation rate; (ii) cell accumulation in
      the S-phase of cell cycle and (iii) proliferating cell nuclear antigen (PCNA)
      expression. We demonstrate that the Ca(2+) uptake into LNCaP cells is mediated by
      TRPV6, with the subsequent downstream activation of the nuclear factor of
      activated T-cell transcription factor (NFAT). TRPV6-mediated Ca(2+) entry is also
      involved in apoptosis resistance of LNCaP cells. Our results suggest that TRPV6
      expression in LNCaP cells is regulated by androgen receptor, however, in a ligand
      independent manner. We conclude that the upregulation of TRPV6 Ca(2+) channel in
      prostate cancer cells may represent a mechanism for maintaining a higher
      proliferation rate, increasing cell survival and apoptosis resistance as well.

PMID- 17533369
TI  - Epidermal growth factor (EGF) activates nuclear factor-kappaB through
      IkappaBalpha kinase-independent but EGF receptor-kinase dependent tyrosine 42
      phosphorylation of IkappaBalpha.
AB  - Overexpression of epidermal growth factor (EGF) receptor and constitutive
      activation of nuclear factor-kappaB (NF-kappaB) are frequently encountered in
      tumor cells. Although EGF has been shown to induce NF-kappaB activation, the
      mechanism is poorly understood. EGF activated NF-kappaB DNA binding, induced NF
      kappaB reporter activity and the expression of antiapoptotic and cell
      proliferative gene products. Interestingly, non-small cell lung adenocarcinoma
      cell lines (HCC827 and H3255), which exhibit EGFR amplification, showed ligand
      independent activation of NF-kappaB. Unlike tumor-necrosis factor (TNF), however,
      EGF failed to induce IkappaBalpha phosphorylation and ubiquitination and the
      activation of IkappaBalpha kinase (IKK). Although DN-IKKbeta inhibited TNF
      induced NF-kappaB activity, DN-IKKbeta had no effect on EGF-induced NF-kappaB
      activation, suggesting that EGF-induced NF-kappaB activation is IKK independent.
      Using dominant-negative plasmids, we also demonstrated the role of TRADD, TRAF2,
      NIK and Ras in EGF-induced NF-kappaB activation. By using specific antibodies and
      IkappaBalpha plasmid, which is mutated at tyrosine 42 to phenylalanine, we show
      that EGF induced the tyrosine phosphorylation of IkappaBalpha at residue 42.
      Furthermore, EGF receptor kinase inhibitor blocked IkappaBalpha phosphorylation
      and consequent NF-kappaB activation. Overall, our results indicate that tyrosine
      phosphorylation of IkappaBalpha at residue 42 is critical for EGF-induced NF
      kappaB activation pathway.

PMID- 17533370
TI  - The tyrosine kinase Abl is required for Src-transforming activity in mouse
      fibroblasts and human breast cancer cells.
AB  - The cytoplasmic tyrosine kinase Src has been implicated in signal transduction
      induced by growth factors and integrins. Src also shows oncogenic activity when
      deregulated. Accumulating evidence indicates that the tyrosine kinase Abl is an
      important substrate for Src signalling in normal cells. Here we show that Abl is
      also required for Src-induced transformation of mouse fibroblasts. Abl does not
      mediate tyrosine phosphorylation of Stat3 and Shc, two important regulators of
      Src oncogenic activity. In contrast, Abl controls the activation of the small
      GTPase Rac for oncogenic signalling and active Rac partly rescued Src
      transformation in cells with inactive Abl. Moreover, Abl mediates Src-induced
      extracellular regulated kinase 5 (ERK5) activation to drive cell transformation.
      Finally, we find that Abl/Rac and Abl/ERK5 pathways also operate in human MCF7
      and BT549 breast cancer cells, where neoplastic transformation depends on Src
      like activities. Therefore, Abl is an important regulator of Src oncogenic
      activity both in mouse fibroblasts and in human cancer cells. Targeting these Abl
      dependent signalling cascades may be of therapeutic value in breast cancers where
      Src-like function is important.

PMID- 17533371
TI  - Amyloid-beta precursor-like protein APLP1 is a novel p53 transcriptional target
      gene that augments neuroblastoma cell death upon genotoxic stress.
AB  - The tumor suppressor p53 is a key modulator of the cellular stress response,
      inducing cell-cycle arrest, apoptosis, senescence and cell differentiation. To
      evaluate further the molecular mechanism underlying p53 function, the
      transcriptional profiles of proliferating and senescent WI-38 cells, both wild
      type p53 expressers and counterparts with an inactivated p53, were compared by
      DNA microarray analysis. In particular, the amyloid-beta precursor-like protein 1
      (APLP1) is induced in senescent cells in a p53-dependent manner. APLP1 was
      confirmed to be a novel transcriptional target of p53 by in vivo and in vitro
      characterization of a p53 responsive element found in the first intron of the
      APLP1 gene locus. APLP1 knockdown experiments demonstrate that APLP1 is required
      for the proliferation of fibroblastic and epithelial cells. Moreover, depletion
      of APLP1 expression diminishes stress-induced apoptosis of neural cells, whereas
      ectopic APLP1 expression augments apoptosis. Based on these data, a mechanism is
      proposed whereby p53-dependent induction of APLP1 is involved in neural cell
      death, and which may exacerbate neuronal cell loss in some acute or chronic
      neurodegenerative disorders.

PMID- 17533372
TI  - The E7 protein from human papillomavirus type 16 enhances keratinocyte migration
      in an Akt-dependent manner.
AB  - Cyclin-dependent kinase inhibitor p27(kip1) (p27) has recently been implicated as
      a positive regulator of cellular motility and is a marker of poor prognosis in
      several forms of cancer when localized to the cytoplasm. Cytoplasmic p27 exerts
      its effect on migration by binding to and inhibiting the activation of the small
      GTPase and cytoskeletal organizer RhoA, consequentially loosening cell substrate
      grip and enhancing movement. Using DNA damage as a p27 nuclear import signal, we
      found that the E7 oncoprotein from human papillomavirus type 16 (HPV-16), the
      etiological agent of cervical cancer, enhanced both the cytoplasmic retention of
      p27 and the migration of human foreskin keratinocytes (HFKs) in a
      phosphoinositide-3 kinase (PI3K)/Akt-dependent manner using a standard wound
      assay. Increased migration in E7-expressing HFKs correlated with an Akt-regulated
      downregulation of RhoA activity through p27 binding under conditions where a p27
      nuclear import signal is given (that is, DNA damage). Under these conditions,
      inhibition of the downstream RhoA effector ROCK enhanced control cell migration,
      whereas relatively unaffecting E7-expressing cells, further implicating that the
      inhibitory effect of E7 on RhoA positively regulates migration. We believe that
      the E7 protein from HPV-16 can modulate the cytoplasmic localization of p27 and
      may in turn regulate tumor metastasis/aggressiveness through the PI3K/Akt
      pathway.

PMID- 17533373
TI  - Cyclin B2 suppresses mitotic failure and DNA re-replication in human somatic
      cells knocked down for both cyclins B1 and B2.
AB  - Cyclin-dependent kinase 1 (CDK1) plays a crucial role in establishing metaphase
      and has also been shown to prevent DNA re-replication. Cyclins B1 and B2 are two
      known activators of CDK1 operating during mitosis in human cells. Little is known
      about the specific roles of each of these cyclins in CDK1 activation, but cyclin
      B2 is thought to play a minor role and to be unable to replace cyclin B1 for
      mitosis completion. In our study, we found that severe reduction by separate RNA
      interference of either cyclin B1 or cyclin B2 protein levels results in little or
      no alteration of the cell cycle and, more specifically, of mitosis progression.
      In contrast, simultaneous depletion of both B-type cyclins leads to massive
      accumulation of 4N cells, mitotic failure, premature mitosis exit and DNA re
      replication. These defects can be corrected by the ectopic expression of a cyclin
      B2 resistant to the short hairpin RNA. Altogether, these data show that, in
      cycling human cells, cyclin B2 can compensate for the downregulation of cyclin B1
      during mitosis. They also clearly implicate cyclins B1 and B2 as crucial
      activators of CDK1 in its biological function of DNA re-replication prevention.

PMID- 17533374
TI  - HIF-1 and NF-kappaB-mediated upregulation of CXCR1 and CXCR2 expression promotes
      cell survival in hypoxic prostate cancer cells.
AB  - Hypoxic cancer cells are resistant to treatment, leading to the selection of
      cells with a more malignant phenotype. The expression of interleukin-8 (IL-8)
      plays an important role in the tumorigenesis and metastasis of solid tumors
      including prostate cancer. Recently, we detected elevated expression of IL-8 and
      IL-8 receptors in human prostate cancer tissue. The objective of the current
      study was to determine whether hypoxia increases IL-8 and IL-8 receptor
      expression in prostate cancer cells and whether this contributes to a survival
      advantage in hypoxic cells. IL-8, CXCR1 and CXCR2 messenger RNA (mRNA) expression
      in PC3 cells was upregulated in response to hypoxia in a time-dependent manner.
      Elevated IL-8 secretion following hypoxia was detected by enzyme-linked
      immunosorbent assay, while immunoblotting confirmed elevated receptor expression.
      Attenuation of hypoxia-inducible factor (HIF-1) and nuclear factor-kappaB (NF
      kappaB) transcriptional activity using small interfering RNA (siRNA), a HIF-1
      dominant-negative and pharmacological inhibitors, abrogated hypoxia-induced
      transcription of CXCR1 and CXCR2 in PC3 cells. Furthermore, chromatin-IP analysis
      demonstrated binding of HIF-1 and NF-kappaB to CXCR1. Finally, inhibition of IL-8
      signaling potentiated etoposide-induced cell death in hypoxic PC3 cells. These
      results suggest that IL-8 signaling confers a survival advantage to hypoxic
      prostate cancer cells, and therefore, strategies to inhibit IL-8 signaling may
      sensitize hypoxic tumor cells to conventional treatments.

PMID- 17533375
TI  - Mutations of the HIPK2 gene in acute myeloid leukemia and myelodysplastic
      syndrome impair AML1- and p53-mediated transcription.
AB  - The AML1 transcription factor complex is the most frequent target of leukemia
      associated chromosomal translocations. Homeodomain-interacting protein kinase 2
      (HIPK2) is a part of the AML1 complex and activates AML1-mediated transcription.
      However, chromosomal translocations and mutations of HIPK2 have not been
      reported. In the current study, we screened mutations of the HIPK2 gene in 50
      cases of acute myeloid leukemia (AML) and in 80 cases of myelodysplastic syndrome
      (MDS). Results indicated there were two missense mutations (R868W and N958I) in
      the speckle-retention signal (SRS) domain of HIPK2. Subcellular localization
      analyses indicated that the two mutants were largely localized to nuclear regions
      with conical or ring shapes, and were somewhat diffused in the nucleus, in
      contrast to the wild type, which were mainly localized in nuclear speckles. The
      mutations impaired the overlapping localization of AML1 and HIPK2. The mutants
      showed decreased activities and a dominant-negative function over wild-type
      protein in AML1- and p53-dependent transcription. These findings suggest that
      dysfunction of HIPK2 may play a role in the pathogenesis of leukemia.

PMID- 17533376
TI  - Oncogenic activation of the Met receptor tyrosine kinase fusion protein, Tpr-Met,
      involves exclusion from the endocytic degradative pathway.
AB  - Multiple mechanisms of dysregulation of receptor tyrosine kinases (RTKs) are
      observed in human cancers. In addition to gain-of-function, loss of negative
      regulation also contributes to oncogenic activation of RTKs. Negative regulation
      of many RTKs involves their internalization and degradation in the lysosome, a
      process regulated through ubiquitination. RTK oncoproteins activated following
      chromosomal translocation, are no longer transmembrane proteins, and are
      predicted to escape lysosomal degradation. To test this, we used the Tpr-Met
      oncogene, generated following chromosomal translocation of the hepatocyte growth
      factor receptor (Met). Unlike Met, Tpr-Met is localized in the cytoplasm and also
      lacks the binding site for Cbl ubiquitin ligases. We determined whether
      subcellular localization of Tpr-Met, and/or loss of its Cbl-binding site, is
      important for oncogenic activity. Presence of a Cbl-binding site and
      ubiquitination of cytosolic Tpr-Met oncoproteins does not alter their
      transforming activity. In contrast, plasma membrane targeting allows Tpr-Met to
      enter the endocytic pathway, and Tpr-Met transforming activity as well as protein
      stability are decreased in a Cbl-dependent manner. We show that transformation by
      Tpr-Met is in part dependent on its ability to escape normal downregulatory
      mechanisms. This provides a paradigm for many RTK oncoproteins activated
      following chromosomal translocation.

PMID- 17533377
TI  - A crosstalk between hSiah2 and Pias E3-ligases modulates Pias-dependent
      activation.
AB  - Protein inhibitor of activated STAT (Pias) and human homologues of seven in
      absentia (hSiah) proteins both exhibit properties of ubiquitin-family peptides
      conjugating enzymes. Pias present E3-ligase activity for small ubiquitin-related
      modifiers (Sumo) covalent attachment to their targets. This post-translational
      modification is responsible for the activation of different transcription factors
      such as AP1. HSiah proteins possess ubiquitin-E3-ligase activity that triggers
      their partners to proteasomal-dependent degradation. The present study identifies
      Pias as a new hSiah2-interacting protein. We demonstrate that hSiah2 regulates
      specifically the proteasome-dependent degradation of Pias proteins. On reverse,
      Pias does not prevent hSiah2 degradation. We provide evidences for hSiah2
      dependent degradation of Pias as being a mechanism in the regulation of c-jun N
      terminal kinase-activating pathways. This report describes a new interconnection
      between sumoylation and ubiquitination pathways by regulating the levels of the
      E3-ligases available for these processes.

PMID- 17533379
TI  - A structural analysis of the obsessional character: a Fairbairnian perspective.
AB  - This paper reviews the object relations model of W.R.D. Fairbairn and applies it
      to the understanding of the obsessional personality. Fairbairn's model sees
      attachment to good objects as the immutable component of normal development.
      Parental failures are seen as intolerable to the child and trigger the splitting
      defense that isolates (via repression) the frustrating aspects of the object
      along with the part of the child's ego that relates only to that part-object.
      This fundamental defense protects the child from the knowledge that he is
      dependent on indifferent objects and preserves his attachment. The split-off part
      self and part-object structures are too disruptive to remain conscious, yet
      despite being repressed make themselves known through repetition compulsions and
      transference. The specific characteristics of families that produce obsessional
      children impact the child's developing ego structures in similar ways. This style
      of developmental history creates predictable self and object configurations in
      the inner world, which then translate via repetition compulsion into obsessional
      behavior in adulthood.

PMID- 17533378
TI  - Indirubin-3'-monoxime inhibits autophosphorylation of FGFR1 and stimulates ERK1/2
      activity via p38 MAPK.
AB  - Indirubin-3'-monoxime is a derivative of the bis-indole alkaloid indirubin, an
      active ingredient of a traditional Chinese medical preparation that exhibits anti
      inflammatory and anti-leukemic activities. Indirubin-3'-monoxime is mainly
      recognized as an inhibitor of cyclin-dependent kinases (CDKs) and glycogen
      synthase kinase-3. It inhibits proliferation of cultured cells, mainly through
      arresting the cells in the G1/S or G2/M phase of the cell cycle. Here, we report
      that indirubin-3'-monoxime is able to inhibit proliferation of NIH/3T3 cells by
      specifically inhibiting autophosphorylation of fibroblast growth factor receptor
      1 (FGFR1), blocking in this way the receptor-mediated cell signaling. Indirubin
      3'-monoxime inhibits the activity of FGFR1 at a concentration lower than that
      required for inhibition of phosphorylation of CDK2 and retinoblastoma protein and
      cell proliferation stimulated by fetal calf serum. The ability of indirubin-3'
      monoxime to inhibit FGFR1 signaling was similar to that of the FGFR1 inhibitor
      SU5402. In addition, we found that indirubin-3'-monoxime activates long-term p38
      mitogen-activated protein kinase activity, which stimulates extracellular signal
      regulated kinase 1/2 in a way unrelated to the activity of FGFR1. Furthermore, we
      show that indirubin-3'-monoxime can inhibit proliferation of the myeloid leukemia
      cell line KG-1a through inhibition of the activity of the FGFR1 tyrosine kinase.
      The data presented here demonstrate previously unknown activities of indirubin-3'
      monoxime that may have clinical implications.

PMID- 17533380
TI  - Ferenczi's clinical and theoretical conception of trauma: a brief introductory
      map.
AB  - In this paper, I am going to limit myself to tracing a map of the principal
      points in Ferenczi's thinking concerning trauma. Ferenczi's contribution to
      trauma theory is fundamental, even though up to today--in spite of the recent
      "Ferenczian Renaissance"--it still remains for many psychoanalysts simply not
      acknowledged and not considered and, when it is acknowledged and considered, it
      is frequently misunderstood or reported only in part. Perhaps this is because
      passages of his theory are extrapolated without knowing his entire clinical
      theoretical way or because he is quoted through others without the authors having
      personally read his work. These last ones are typical habits, as we know, to
      project one's own ideas, especially our prejudices.

PMID- 17533381
TI  - Primal fatherhood and primal rage.
AB  - Fatherhood may unconsciously activate repudiated identifications with patriarchal
      primal fathers in men with progressive social values. These men may consciously
      cultivate an image of themselves as rebellious nonconformists. These men may wish
      to raise children who are fiercely independent just like them. Yet when these
      rambunctious children challenge paternal authority, these men may become enraged
      because their unconscious identification with the primal father has been
      threatened. These men may be referred to treatment for problems of anger
      management. They tend to unconsciously re-create and enact their conflicted and
      enraging relationship with the primal father in their relationship with the
      therapist.

PMID- 17533382
TI  - The possibility of multiple models for Oedipal development.
AB  - For nearly 100 years and at least in certain prominent psychoanalytic subgroups,
      the Oedipus complex remained a defining construct that determined a boundary for
      those within and outside psychoanalysis. The time is ripe for reconsidering its
      culture-specific and variable nature and its failure inter alia to explain with
      any degree of cogency ongoing internecine conflict in a community of clinicians
      and theoreticians who have had the benefit of oedipally mediated training
      analyses.

PMID- 17533383
TI  - The models of Picasso's rose period: The Family of Saltimbanques.
AB  - The word "model" in this context has a variety of meanings. The concept of
      "model" encompasses the external person who is represented by the artist, as well
      as the internal, conscious and unconscious, past and present mental
      representations of other individuals and the work of other artists. In all of
      these meanings, the relationships of artist and model have been quite specific to
      the artist under consideration and the historical-cultural period. For Picasso,
      the relationship of artist and model was particularly intense, reflecting myriad
      aspects of his personality and artistic development. The theme of artist and
      model was the subject of many of his paintings and graphic works. We focus
      particularly on his use of harlequins, saltimbanques, and circus performers
      during his blue and rose periods. The change in predominant models and moods
      between periods is noted. Among the issues considered is the relevance of these
      models in this particular period. Why were they especially salient objects for
      identification and for his artistic identity? Identification with the model may
      represent or be linked to earlier identifications of adolescence and childhood.
      We discuss the implications of these portrayals for his object relationships and
      the magical power, possession, and control in the development of his art. The
      painting "The Family of Saltimbanques," his most ambitious work to date, the
      integration and culmination of this theme during this period, is of particular
      interest.

PMID- 17533388
TI  - A phase I trial of S-1 with concurrent radiotherapy for locally advanced
      pancreatic cancer.
AB  - This study investigated the maximum tolerated dose of S-1 based on the frequency
      of its dose-limiting toxicities (DLT) with concurrent radiotherapy in patients
      with locally advanced pancreatic cancer. S-1 was administered orally at
      escalating doses from 50 to 80 mg m(-2) b.i.d. on the day of irradiation during
      radiotherapy. Radiation therapy was delivered through four fields as a total dose
      of 50.4 Gy in 28 fractions over 5.5 weeks, and no prophylactic nodal irradiation
      was given. Twenty-one patients (50 three; 60 five; 70 six; 80 mg m(-2) seven
      patients) were enrolled in this trial. At a dose of 70 mg m(-2) S-1, two of six
      patients demonstrated DLT involving grade 3 nausea and vomiting and grade 3
      haemorrhagic gastritis, whereas no patients at doses other than 70 mg m(-2)
      demonstrated any sign of DLT. Among the 21 enrolled patients, four (19.0%) showed
      a partial response. The median progression-free survival time and median survival
      time for the patients overall were 8.9 and 11.0 months, respectively. The
      recommended dose of S-1 therapy with concurrent radiotherapy is 80 mg m(-2) day(
      1). A multi-institutional phase II trial of this regimen in patients with locally
      advanced pancreatic cancer is now underway.

PMID- 17533389
TI  - Adjuvant imatinib treatment improves recurrence-free survival in patients with
      high-risk gastrointestinal stromal tumours (GIST).
AB  - Palliative imatinib treatment has dramatically improved survival in patients with
      malignant gastrointestinal stromal tumours, particularly in patients with tumours
      harbouring activating KIT mutations. To evaluate the effectiveness of adjuvant
      imatinib after radical surgery, a consecutive series of patients with high-risk
      tumours (n=23) was compared with historic controls (n=48) who were treated with
      surgery alone. The mean follow-up period was over 3 years in both groups. Only 1
      out of 23 patients (4%) in the adjuvant treatment group developed recurrent
      disease compared to 32 out of 48 patients (67%) in the control group. This
      preliminary study indicates that 1 year of adjuvant treatment with imatinib
      dramatically improves recurrence-free survival. Confirmation of these findings
      awaits the results of ongoing randomised studies.

PMID- 17533390
TI  - Cellular and humoral mechanisms of osteoclast formation in Ewing's sarcoma.
AB  - Cellular mechanisms that account for tumour osteolysis associated with Ewing's
      sarcoma are uncertain. Osteoclasts are marrow-derived multinucleated cells (MNCs)
      that effect tumour osteolysis. Osteoclasts are known to form from macrophages by
      both receptor activator for nuclear factor-kappaB (RANK) ligand (RANKL)-dependent
      and -independent mechanisms. In this study, our aim has been to determine whether
      tumour-associated macrophages (TAMs) isolated from Ewing's sarcoma are capable of
      differentiating into osteoclasts and to characterise the cellular and humoral
      mechanisms whereby this occurs. Tumour-associated macrophages were isolated from
      two Ewing's sarcomas and cultured on both coverslips and dentine slices for up to
      21 days with soluble RANKL and macrophage colony stimulating factor (M-CSF).
      Osteoclast formation from TAMs (CD14+) was evidenced by the formation of tartrate
      resistant acid phosphatase (TRAP) and vitronectin receptor (VNR)-positive MNCs,
      which were capable of carrying out lacunar resorption. This osteoclast formation
      was inhibited by the addition of bisphosphonates. Both Ewing's sarcoma-derived
      fibroblasts and some bone stromal cells expressed RANKL and supported osteoclast
      formation by a contact-dependent mechanism. We also found that osteoclast
      differentiation occurred when Ewing's TAMs were cultured with tumour necrosis
      factor (TNF)-alpha in the presence of M-CSF and that TC71 Ewing's sarcoma cells
      stimulated osteoclast formation through the release of a soluble factor, the
      action of which was abolished by an antibody to TNF-alpha. These results indicate
      that TAMs in Ewing's sarcoma are capable of osteoclast differentiation by both
      RANKL-dependent and TNF-alpha-dependent mechanisms and that Ewing's sarcoma cells
      produce osteoclastogenic factor(s). Our findings suggest that anti-resorptive and
      anti-osteoclastogenic therapies may be useful in inhibiting the osteolysis of
      Ewing's sarcoma.

PMID- 17533391
TI  - Recent increase of breast cancer incidence among women under the age of forty.
AB  - Using data from the Geneva Cancer Registry, we found that in 2002-2004, breast
      cancer incidence in women aged 25-39 years increased by 46.7% per year (95% CI:
      7.1-74.0, P=0.015), which surveillance or detection bias may not fully explain.

PMID- 17533392
TI  - Melanoma incidence and mortality in Scotland 1979-2003.
AB  - We studied 12,450 cases of invasive melanoma diagnosed in Scotland in 1979-2003,
      by thickness, pathological type, and body site at ages under 40, 40-59, and 60
      years and over. Melanoma incidence trebled in males from 3.57 to 10.93/10(5) per
      year, and increased 2.3-fold in females from 5.60 to 12.96/10(5) per year. The
      rate of increase fell in each successive 5-year period. The greatest increase was
      in males aged 60 years and over at diagnosis. Significant incidence increases
      were seen in melanomas < 1 mm in all three age groups, but those > 4 mm only
      increased significantly at ages 60 years and over. All histological types
      increased significantly at ages 60 years and over, and in this age group the
      greatest increase was seen on the head and neck. Five-year disease-free survival
      improved steadily. Survival figures for 1994-1998 ranged from 93.6% for males and
      95.8% for females with tumours < 1 mm, to 52.4 and 48.3%, respectively, for those
      with tumours > 4 mm. Over the 25 years, melanoma mortality doubled in males from
      1.1 to 2.4/10(5) per year, but was unchanged in females at 1.5/10(5) per year.
      Public education on melanoma is required both for primary prevention and earlier
      diagnosis, particularly for older males.

PMID- 17533394
TI  - A prospective randomized comparison of diagnostic efficacy between transperineal
      and transrectal 12-core prostate biopsy.
AB  - The aim of this study is to elucidate the diagnostic efficacy between
      transperineal and transrectal 12-core prostate biopsy for prostate cancer. We
      prospectively randomized 200 consecutive men into two groups to undergo
      systematic prostate biopsy. Overall positivity for cancer was similar (47% by
      transperineal and 53% by transrectal; P=0.480). However, in case with 'gray zone'
      PSA (from 4.1 to 10.0 ng/ml), significantly more cores were positive when
      approach was transperineal, especially among transition zone cores. Therefore,
      urologist preferences are sufficient for choosing an approach, except for a
      possible small advantage of transperineal biopsy when PSA is in gray zone.

PMID- 17533395
TI  - The influence of alpha1-antagonist on the expression pattern of TNF receptor
      family in primary culture of prostate epithelial cells from BPH patients.
AB  - Doxazosin triggers apoptosis via an imprecisely defined receptor mechanism that
      is related to tumor necrosis factor receptors (TNFRs). The aim of this study was
      to determine CD95, TNFR-1, TNFR-2, CD40 expression in primary prostate epithelial
      cultures incubated with doxazosin. Epithelial cultures were cultivated from 10
      benign prostate hyperplasia patients. The cells were incubated with 20, 50 and 80
      microM of doxazosin. Apoptosis was confirmed by fluorescence microscopy and flow
      cytometry. The cells were analyzed for expression of FAS, CD40, TNFR-1 and TNFR-2
      by flow cytometry. Early apoptotic cells were present in all groups. A positive
      correlation was noticed between doxazosin dose and TNFR-1-, -2-positive cells. A
      decrease of CD40-positive cell population was observed in the lowest
      concentration. A decrease of mean fluorescence intensity signal of CD40 and CD95
      was observed in the lowest concentration. Doxazosin-triggered apoptosis was dose
      independent. The initiation of apoptosis was a result of receptors 'crosstalk'
      rather than a single receptor pathway activation. TNF receptor self-assembly
      process should be checked as a potential mechanism leading to apoptosis after
      doxazosin treatment.

PMID- 17533396
TI  - Prognostic significance of folate metabolism polymorphisms for lung cancer.
AB  - Functional nonsynonymous single-nucleotide polymorphisms (nsSNPs) of folate
      metabolism genes can influence the methylation of tumour suppressor genes,
      thereby potentially impacting on tumour behaviour. To investigate whether such
      polymorphisms influence lung cancer survival, we genotyped 14 nsSNPs mapping to
      methylene-tetrahydrofolate reductase (MTHFR), methionine synthase (MTR),
      methionine synthase reductase (MTRR); DNA methyltransferase (DNMT2),
      methylenetetrahydrofolate dehydrogenase (MTHFD1) and methenyltetrahydrofolate
      synthetase (MTHFS) in 619 Caucasian women with incident disease, 465 with non
      small cell (NSCLC) and 154 with small cell lung cancer (SCLC). The most
      significant association detected was with MTHFS Thr202Ala, with carriers of
      variant alleles having a worse prognosis (hazard ratio (HR)=1.49; 95% confidence
      interval: 1.14-1.94). Associations were also detected between overall survival
      (OS) in SCLC and homozygosity for MTHFR 222Val (HR=1.92; 1.03-3.58) and between
      OS from NSCLC and MTRR 175Leu carrier status (HR=1.36; 1.06-1.75). While there is
      evidence that variation in the folate metabolism genes may influence prognosis
      from lung cancer, current data are insufficiently robust to distinguish
      individual patient outcome.

PMID- 17533397
TI  - Inhibition of epidermal growth factor receptor signalling reduces hypercalcaemia
      induced by human lung squamous-cell carcinoma in athymic mice.
AB  - The purpose of this study was to evaluate the role of the epidermal growth factor
      receptor (EGFR) in parathyroid hormone-related protein (PTHrP) expression and
      humoral hypercalcaemia of malignancy (HHM), using two different human squamous
      cell carcinoma (SCC) xenograft models. A randomised controlled study in which
      nude mice with RWGT2 and HARA xenografts received either placebo or gefitinib 200
      mg kg(-1) for 3 days after developing HHM. Effectiveness of therapy was evaluated
      by measuring plasma calcium and PTHrP, urine cyclic AMP/creatinine ratios, and
      tumour volumes. The study end point was at 78 h. The lung SCC lines, RWGT2 and
      HARA, expressed high levels of PTHrP mRNA as well as abundant EGFR protein, but
      very little erbB2 or erbB3. Both lines expressed high transcript levels for the
      EGFR ligand, amphiregulin (AREG), as well as, substantially lower levels of
      transforming growth factor-alpha (TGF-alpha), and heparin binding-epidermal
      growth factor (HB-EGF) mRNA. Parathyroid hormone-related protein gene expression
      in both lines was reduced 40-80% after treatment with 1 muM of EGFR tyrosine
      kinase inhibitor PD153035 and precipitating antibodies to AREG. Gefitinib
      treatment of hypercalcaemic mice with RWGT2 and HARA xenografts resulted in a
      significant reduction of plasma total calcium concentrations by 78 h. Autocrine
      AREG stimulated the EGFR and increased PTHrP gene expression in the RWGT2 and
      HARA lung SCC lines. Inhibition of the EGFR pathway in two human SCC models of
      HHM by an anilinoquinazoline demonstrated that the EGFR tyrosine kinase is a
      potential target for antihypercalcaemic therapy.

PMID- 17533398
TI  - Circulating insulin-like growth factor axis and the risk of pancreatic cancer in
      four prospective cohorts.
AB  - Insulin-like growth factor (IGF)-I induces growth in pancreatic cancer cells and
      blockade of the IGF-I receptor has antitumour activity. The association of plasma
      IGF-I and IGF binding protein-3 (IGFBP-3) with pancreatic cancer risk has been
      investigated in two small studies, with conflicting results. We conducted a
      nested case-control study within four large, prospective cohorts to investigate
      whether prediagnostic plasma levels of IGF-I, IGF-II, and IGFBP-3 were associated
      with pancreatic cancer risk. Plasma levels in 212 cases and 635 matched controls
      were compared by conditional logistic regression, with adjustment for other known
      pancreatic cancer risk factors. No association was observed between plasma levels
      of IGF-I, IGF-II, or IGFBP-3 and incident diagnosis of pancreatic cancer.
      Relative risks for the highest vs the lowest quartile of IGF-I, IGF-II, and IGFBP
      3 were 0.94 (95% confidence interval (CI), 0.60-1.48), 0.96 (95% CI, 0.61-1.52),
      and 1.21 (95% CI, 0.75-1.92), respectively. The relative risk for the molar ratio
      of IGF-I and IGFBP-3, a surrogate measure for free IGF-I, was 0.84 (95% CI, 0.54
      1.31). Additionally, no association was noted in stratified analyses or when
      requiring longer follow-up. In four prospective cohorts, we found no association
      between the risk of pancreatic cancer and prediagnostic plasma levels of IGF-I,
      IGF-II, or IGFBP-3.

PMID- 17533399
TI  - Combined modality chemoradiation in elderly oesophageal cancer patients.
AB  - We present a single institution experience with 5-FU, mitomycin-C based
      chemoradiation for the primary treatment of elderly patients with oesophageal
      cancer. Twenty-five patients with a median age of 77 years (range 66-88) with a
      diagnosis of stage II-III squamous cell or adenocarcinoma of the oesophagus were
      treated at Memorial Sloan Kettering from 1996 to 2001 with two cycles of
      concurrent 5-FU, mitomycin-C and 50.4 Gy. Owing to age and comorbidity, these
      patients were not considered surgical candidates. The Charlson comorbidity score
      was used to evaluate patient comorbidity. Nine patients (36%) experienced grade 3
      4 haematologic toxicity. Of the 23 patients evaluable for response, 17 patients
      (68%) had a negative post-treatment endoscopy and CT scan without evidence of
      progressive disease. Eleven patients (44%) are alive and 10 (40%) remain without
      evidence of recurrent or progressive oesophageal cancer at a median follow-up of
      35 months. The median overall survival was 35 months and 2-year survival 64%.
      There was no significant difference in overall survival between Charlson score
      </=2 and those with a score >/=2 (P=0.10). Similar survival was observed for
      patients with adenocarcinoma or squamous carcinoma. Primary chemoradiation with
      two cycles of 5-FU, mitomycin-C, and 50.4 Gy in elderly patients is an active
      regimen with moderate toxicity, despite the advanced age and heavy comorbidity
      burden of this cohort. Patients with local/regional oesophageal cancer with
      adequate functional status should not be excluded from potentially curative
      treatment based on age alone.

PMID- 17533400
TI  - Chromosome 9p21 gene copy number and prognostic significance of p16 in ESFT.
AB  - Chromosome 9p21 gene copy number in Ewing's sarcoma family of tumour (ESFT) cell
      lines and primary ESFT has been evaluated using Multiplex Ligation-dependent
      probe amplification, and the clinical significance of CDKN2A loss and
      p16/p14(ARF) expression investigated. Homozygous deletion of CDKN2A was
      identified in 4/9 (44%) of ESFT cell lines and 4/42 (10%) primary ESFT; loss of
      one copy of CDKN2A was identified in a further 2/9 (22%) cell lines and 2/42 (5%)
      tumours. CDKN2B was co-deleted in three (33%) cell lines and two (5%) tumours. Co
      deletion of the MTAP gene was observed in 1/9 (11%) cell lines and 3/42 (7%)
      tumours. No correlation was observed between CDKN2A deletion and clinical
      parameters. However, co-expression of high levels of p16/p14(ARF) mRNA predicted
      a poor event-free survival (P=0.046, log-rank test). High levels of p16/p14(ARF)
      mRNA did not correlate with high expression of p16 protein. Furthermore, p16
      protein expression did not predict event-free or overall survival. Methylation is
      not a common mechanism of p16 gene silencing in ESFT. These studies demonstrate
      that loss (homozygous deletion or single copy) of CDKN2A was not prognostically
      significant in primary ESFT. However, high levels of p16/p14(ARF) mRNA expression
      were predictive of a poor event-free survival and should be investigated further.

PMID- 17533401
TI  - Changing pattern of the detection of locoregional relapse in breast cancer: the
      Edinburgh experience.
AB  - The guidelines for follow-up of breast cancer patients concentrate on the first 3
      5 years, with either reduced frequency of visits or discharge after this. They
      also recommend mammography, but no evidence exists to inform frequency. We
      analyse treatable relapses in our unit from 1312 patients with early stage breast
      cancer treated by breast conserving surgery (BCS) and postoperative radiotherapy
      between 1991 and 1998 to assess appropriateness of the guidelines. A total of 110
      treatable relapses were analysed. Treatable relapse developed at 1-1.5% per year
      throughout follow-up. Forty-eight relapses were in ipsilateral breast, 25
      ipsilateral axilla, 35 contralateral breast, 2 both breasts simultaneously.
      Thirty-seven relapses (33.5%) were symptomatic, 56 (51%) mammographically
      detected, 15 (13.5%) clinically detected, 2 (2%) diagnosed incidentally.
      Mammography detected 5.37 relapses per 1000 mammograms. Patients with symptomatic
      or mammographically detected ipsilateral breast relapse had significantly longer
      survival from original diagnosis (P=0.0002) and from recurrence (P=0.0014)
      compared with clinically detected. Treatable relapse occurs at a constant rate
      for at least 10 years. Clinical examination detects a minority (13.5%). Relapse
      diagnosed clinically is associated with poorer outcome. Long-term follow-up based
      on regular mammography is warranted for all patients treated by BCS.

PMID- 17533402
TI  - Predictors of ovarian reserve in young women with breast cancer.
AB  - Ovarian reserve can be diminished following treatment for breast cancer. This
      study evaluated biochemical and biophysical parameters of ovarian reserve in
      these patients. Biochemical and biophysical tests of ovarian reserve were
      performed simultaneously in young (age 22-42 years), regularly menstruating women
      with breast cancer (n=22) and age-matched controls (n=24). All tests were
      performed before (baseline) and after transient ovarian stimulation in the early
      follicular phase. Patients were recruited both before and after completion of
      chemotherapy, with some patients being followed up prospectively. Serum samples
      were analysed for follicle-stimulating hormone (FSH), luteinising hormone (LH),
      oestradiol (E(2)), inhibins A and B, and antimullerian hormone (AMH). Biophysical
      (ultrasound) tests included ovarian volume, antral follicle count (AFC), ovarian
      stromal blood flow and uterine dimensions. Significant differences were revealed
      (when compared with the controls) for basal FSH (11.32+/-1.48 vs 6.62+/-0.42 mIU
      ml(-1), P<0.001), basal AMH (0.95+/-0.34 vs 7.89+/-1.62 ng ml(-1), P<0.001) and
      basal inhibin B (19.24+/-4.56 vs 83.61+/-13.45 pg ml(-1), P<0.001). Following
      transient ovarian stimulation, there were significant differences in the
      increment change (Delta) for inhibin B (3.02+/-2.3 vs 96.82+/-16.38 pg ml(-1),
      P<0.001) and E(2) (107.8+/-23.95 vs 283.2+/-40.34 pg ml(-1), P<0.01). AFC was the
      only biophysical parameter that was significantly different between patients and
      the controls (7.80+/-0.85 vs 16.77+/-1.11, P<0.001). Basal and stimulated
      biochemical (serum AMH, FSH, inhibin B and E(2)) and biophysical (AFC) tests may
      be potential markers of ovarian reserve in young women with breast cancer.

PMID- 17533403
TI  - Outcome of a risk-related therapeutic strategy used prospectively in a population
      based study of Hodgkin's lymphoma in adolescents.
AB  - The aim was to assess outcome in a population-based cohort of adolescents with
      Hodgkin's lymphoma (HL) diagnosed in the UK's northern region over a 10-year
      period. Among a population of 3.09 million, 55 of 676 patients (8%) diagnosed
      with HL were aged 13-19. Seven had nodular lymphocyte-predominant HL, 48
      classical HL (cHL). Of the latter, 36 were >or=16 years. Application of the
      Scottish and Newcastle Lymphoma Group (SNLG) prognostic index meant 21 patients
      were considered high risk (index >or=0.5). They received PVACEBOP multi-agent
      chemotherapy as primary therapy. Standard risk patients (SNLG index <0.5) were
      treated with standard ChlVPP or ABVD chemotherapy+/-radiotherapy. Scottish and
      Newcastle Lymphoma Group indexing is not valid for patients under 16. Twelve
      patients therefore received UKCCSG protocols (n=8), ABVD plus radiotherapy (n=2),
      or PVACEBOP (n=2). Forty-six patients with cHL (96%) achieved complete remission.
      Seven patients relapsed but all entered complete remission after salvage therapy.
      Five patients died: three of HL, one in an accident and one of disseminated
      varicella complicating cystic fibrosis. Five- and 10-year overall survival was 93
      and 86%, respectively; disease-specific survival was 95 and 92%. The data suggest
      that older adolescents with high-risk HL require intensive protocols as primary
      therapy to secure optimal outcome.

PMID- 17533404
TI  - Residential mobility and risk of childhood acute lymphoblastic leukaemia: an
      ecological study.
AB  - We conducted an ecological analysis of childhood acute lymphoblastic leukaemia
      incidence data from children <or=5 years old during 1992-1998 from the
      Surveillance, Epidemiology, and End Results Program in 200 counties and Hawaii.
      The response variable was the count of cases in each county race-sex stratum,
      examined in relation to data from the United States Census and the United States
      Department of Agriculture. The final models for both sexes included race,
      proportion moved during 1985-1990, and proportion of households with income
      >or=$5000 as potential predictors. Incidence was lower among black boys (rate
      ratio (RR)=0.5) and black girls (RR=0.4) than among other children of the same
      sex; no other significant racial differences were detected. Incidence was
      elevated among males (but not females) residing in counties where >or=50% of the
      population relocated (RR=1.5) and among females (but not males) residing in
      counties where <6% of the households had incomes <$5000 (RR=1.5). These sex
      differences in risk factors were unexpected.

PMID- 17533410
TI  - Exaggerated claim about adaptive thermogenesis.

PMID- 17533411
TI  - Use of gene profiling to describe a niche for dendritic cell development.
AB  - Gene profiling provides a multitude of data on individual gene expression. The
      view is expressed here that unreplicated data can be used in a descriptive way to
      compare cell populations in terms of their lineage characteristics and function.
      In these studies, the aim is to provide a snapshot of gene expression or its
      absence as a reflection of cell lineage or type, rather than gain a reliable
      expression measure for all genes expressed. The data set used in this analysis
      represents gene expression in the splenic stroma STX3 supportive of dendritic
      cell hematopoiesis and the lymph node stroma 2RL22, which is non-supportive.
      These were obtained by hybridization of Affymetrix U74Av2 genechips. The use of P
      value selection to identify genes with a high probability of differential
      expression has been used effectively to detect differentially expressed genes.
      Genes that relate to a niche environment for hematopoiesis have been selected for
      further study to make predictions about the cell types of supportive stroma.

PMID- 17533412
TI  - Autoimmunity: the nuclear arsenal of autoimmunity.

PMID- 17533413
TI  - Influence of dietary fats on Ecstasy-induced hyperthermia.
AB  - BACKGROUND AND PURPOSE: Studies were designed to examine the effects of dietary
      fats on metabolic effects of 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy).
      These effects included hyperthermia, expression of uncoupling protein (UCP1 and
      3) in brown adipose tissue or skeletal muscle and plasma free fatty acid (FFA)
      levels. EXPERIMENTAL APPROACH: Male Sprague-Dawley rats were fed either a high
      fat diet (HFD, 60% kcal) or a lower fat isocaloric controlled diet (LFD, 10%
      kcal) for 28 days before MDMA challenge. KEY RESULTS: No significant differences
      were observed between LFD and HFD groups in terms of body weight, plasma
      thyroxine (T4) levels and expression of brown fat UCP1 or skeletal muscle UCP3
      protein. HFD significantly raised levels of circulating FFA and potentiated the
      thermogenesis induced by MDMA (10 mg kg(-1), s.c.), compared to the effects of
      the LFD. Moreover, 30 and 60 min after MDMA administration, plasma FFA levels
      decreased in HFD animals, but were markedly elevated in the LFD group.
      CONCLUSIONS AND IMPLICATIONS: These results indicate that high-fat feeding
      regulates MDMA-induced thermogenesis by augmenting the activation of UCP rather
      than its expression.

PMID- 17533414
TI  - Therapeutic treatment with poly(ADP-ribose) polymerase inhibitors attenuates the
      severity of acute pancreatitis and associated liver and lung injury.
AB  - BACKGROUND AND PURPOSE: The mortality associated with acute pancreatitis (AP) is
      largely attributable to abnormalities that occur in distant organs and supportive
      care remains the only treatment for patients with these complications. Recently,
      prophylactic pharmacological blockade of poly(ADP-ribose) polymerase (PARP)
      enzymes has been shown to attenuate the severity of the disease. However, the
      clinical relevance of PARP inhibitors administered after the onset of AP remains
      uncertain. The aim of the present study was to investigate the therapeutic
      effects of PARP inhibitors in established AP. EXPERIMENTAL APPROACH: Mice were
      fed a choline/methionine-deficient/ethionine-supplemented (CMDE) diet to induce
      AP. PARP inhibitors were given at 36 h after the onset of CMDE diet. Severity of
      pancreatitis was assessed by measurements of serum amylase, lipase, IL-1beta and
      IL-6, and histological grading. Serum hepatic enzymes, myeloperoxidase (MPO)
      activity and morphological changes were measured as indicators of hepatic insult.
      Lung injury was evaluated by MPO activity and morphological changes. Survival
      rates of mice were monitored for 7 days. KEY RESULTS: CMDE diet administration
      resulted in a significant increase in serum amylase, lipase, IL-1beta, IL-6,
      alanine aminotransferase and aspartate aminotranferase levels, indicating AP and
      associated liver injury. Analysis of the histopathological changes in pancreas,
      liver and lung revealed extensive tissue damage. Treatment of mice with PARP
      inhibitors after the onset of AP was associated with a reduction in the severity
      of AP and, accordingly, with a reduced mortality rate. CONCLUSIONS AND
      IMPLICATIONS: Our results support the therapeutic application of PARP inhibitors
      in the treatment of established AP.

PMID- 17533415
TI  - Chemogenomic approaches to drug discovery: similar receptors bind similar
      ligands.
AB  - Within recent years, a paradigm shift from traditional receptor-specific studies
      to a cross-receptor view has taken place within pharmaceutical research to
      increase the efficiency of modern drug discovery. Receptors are no longer viewed
      as single entities but grouped into sets of related proteins or receptor families
      that are explored in a systematic manner. This interdisciplinary approach
      attempting to derive predictive links between the chemical structures of
      bioactive molecules and the receptors with which these molecules interact is
      referred to as chemogenomics. Insights from chemogenomics are used for the
      rational compilation of screening sets and for the rational design and synthesis
      of directed chemical libraries to accelerate drug discovery.

PMID- 17533416
TI  - Chemogenomic approaches to rational drug design.
AB  - Paradigms in drug design and discovery are changing at a significant pace.
      Concomitant to the sequencing of over 180 several genomes, the high-throughput
      miniaturization of chemical synthesis and biological evaluation of a multiple
      compounds on gene/protein expression and function opens the way to global drug
      discovery approaches, no more focused on a single target but on an entire family
      of related proteins or on a full metabolic pathway. Chemogenomics is this
      emerging research field aimed at systematically studying the biological effect of
      a wide array of small molecular-weight ligands on a wide array of macromolecular
      targets. Since the quantity of existing data (compounds, targets and assays) and
      of produced information (gene/protein expression levels and binding constants)
      are too large for manual manipulation, information technologies play a crucial
      role in planning, analysing and predicting chemogenomic data. The present review
      will focus on predictive in silico chemogenomic approaches to foster rational
      drug design and derive information from the simultaneous biological evaluation of
      multiple compounds on multiple targets. State-of-the-art methods for navigating
      in either ligand or target space will be presented and concrete drug design
      applications will be mentioned.

PMID- 17533417
TI  - Localization of intracellular compartments that exchange Na,K-ATPase molecules
      with the plasma membrane in a hormone-dependent manner.
AB  - BACKGROUND AND PURPOSE: Dopamine is a major regulator of sodium reabsorption in
      proximal tubule epithelia. By binding to D1-receptors, dopamine induces
      endocytosis of plasma membrane Na,K-ATPase, resulting in a reduced capacity of
      the cells to transport sodium, thus contributing to natriuresis. We have
      previously demonstrated several aspects of the molecular mechanism by which
      dopamine induces Na,K-ATPase endocytosis; however, the location of intracellular
      compartments containing Na,K-ATPase molecules has not been identified.
      EXPERIMENTAL APPROACH: In this study, we used different approaches to determine
      the localization of Na,K-ATPase-containing intracellular compartments. By
      expression of fluorescent-tagged Na,K-ATPase molecules in opossum kidney cells, a
      cell culture model of proximal tubule epithelia, we used fluorescence microscopy
      to determine cellular distribution of the fluorescent molecules and the effects
      of dopamine on this distribution. By labelling cell surface Na,K-ATPase molecules
      from the cell exterior with either biotin or an epitope-tagged antibody, we
      determined the localization of the tagged Na,K-ATPase molecules after endocytosis
      induced by dopamine. KEY RESULTS: In cells expressing fluorescent-tagged Na,K
      ATPase molecules, there were intracellular compartments containing Na,K-ATPase
      molecules. These compartments were in very close proximity to the plasma
      membrane. Upon treatment of the cells with dopamine, the fluorescence labelling
      of these compartments was increased. The labelling of these compartments was also
      observed when the endocytosis of biotin- or antibody-tagged plasma membrane Na,K
      ATPase molecules was induced by dopamine. CONCLUSIONS AND IMPLICATIONS: The
      intracellular compartments containing Na,K-ATPase molecules are located just
      underneath the plasma membrane.

PMID- 17533418
TI  - Apoptotic mimicry: phosphatidylserine liposomes reduce inflammation through
      activation of peroxisome proliferator-activated receptors (PPARs) in vivo.
AB  - BACKGROUND AND PURPOSE: Recently, there has been much attention paid to
      understanding the molecular mechanisms underlying apoptosis and the functional
      consequences of apoptotic body clearance by phagocytes. In an attempt to
      investigate this latter aspect, the present study evaluated the anti-inflammatory
      effects of in vivo administration of phosphatidylserine (PS) liposomes, a well
      characterised membrane component expressed during apoptosis. The participation of
      peroxisome proliferator-activated receptors (PPARs) in PS-mediated effects was
      also investigated. EXPERIMENTAL APPROACH: The anti-inflammatory effect of PS
      liposomes on the delayed phase of carrageenan mouse paw oedema was studied. PS
      liposomes were injected at different doses and times, after carrageenan. Hind
      paws were collected for evaluation of interleukin-1beta (IL-1beta) levels,
      myeloperoxidase (MPO) and N-acetyl-glucosaminidase (NAG) activities and Evans
      blue dye leakage. Participation of PPAR pathways was explored by using PPAR
      antagonists (BADGE and GW9662). KEY RESULTS: Administration of PS, but not
      phosphatidylcholine (PC), liposomes (20-200 mg kg(-1), i.p., 8 h after
      carrageenan) reduced the paw oedema in a dose-dependent manner. PS liposomes were
      effective even when administered 24 and 48 h after carrageenan, a time at which
      indomethacin (1 mg kg(-1), i.p.) had no significant effects. Carrageenan-induced
      Evans blue leakage and IL-1beta production was decreased in PS-treated paws. The
      PPAR antagonists (BADGE and GW9662) partially prevented the anti-inflammatory
      effects of PS administration. CONCLUSIONS AND IMPLICATIONS: PS liposomes have
      anti-inflammatory effects in vivo that are at least partly dependent on PPAR
      activation. Therapeutic strategies mimicking apoptosis may be useful for the
      treatment of inflammatory disorders.

PMID- 17533419
TI  - Treprostinil potentiates the positive inotropic effect of catecholamines in adult
      rat ventricular cardiomyocytes.
AB  - BACKGROUND AND PURPOSE: Prostanoids have been shown to improve exercise
      tolerance, hemodynamics and quality of life in patients with pulmonary arterial
      hypertension (PAH). We investigated whether treprostinil exerts direct
      contractile effects on cardiomyocytes that may explain partly the beneficial
      effects of these drugs. EXPERIMENTAL APPROACH: Ventricular cardiomyocytes from
      adult rats were paced at a constant frequency of 0.5 to 2.0 Hz and cell
      shortening was monitored via a cell edge detection system. Twitch amplitudes,
      expressed as percent cell shortening of the diastolic cell length, and maximal
      contraction velocity, relaxation velocity, time to peak of contraction and time
      to reach 50% of relaxation were analyzed. KEY RESULTS: Treprostinil (0.15 - 15 ng
      ml(-1)) slightly increased contractile dynamics of cardiomyocytes at clinically
      relevant concentrations. However, the drug significantly improved cell shortening
      of cardiomyocytes in the presence of isoprenaline, a beta-adrenoceptor agonist.
      Treprostinil exerted this effect at all beating frequencies under investigation.
      Treprostinil mimicked this potentiating effect in a Langendorff preparation as
      well. The potentiating effect of treprostinil on isoprenaline-dependent cell
      shortening was no longer seen after phosphodiesterase inhibition. Long-term
      cultivation of cardiomyocytes with treprostinil did not modify load free cell
      shortening of these cells, but reduces the duration of contraction. CONCLUSIONS
      AND IMPLICATIONS: We conclude that the clinically used prostanoid treprostinil
      potentiates the positive inotropic effects of catecholamines in adult ventricular
      cardiomyocytes. This newly described effect may contribute to the beneficial
      clinical effects of prostanoids in patients with PAH.

PMID- 17533420
TI  - Size-fractionated heparins have differential effects on human neutrophil function
      in vitro.
AB  - BACKGROUND AND PURPOSE: Heparin is known to possess a range of activities, other
      than effects on blood coagulation, many of which are anti-inflammatory. Effects
      with potential anti-inflammatory applications include the inhibition of elastase
      release from neutrophils, as well as the adhesion of these cells to vascular
      endothelium. In the present study we aimed to investigate whether fractionation
      of heparin may yield molecules with enhanced or specific effects on human
      neutrophil function. EXPERIMENTAL APPROACH: Fractions of defined molecular size
      were obtained from heparin by different methods and assessed for their effects on
      elastase release induced by formyl Met-Leu-Phe (fMLP), from neutrophils, in some
      cases following the priming of these cells with tumour necrosis factor-alpha (TNF
      alpha). Effects of the fractions on neutrophil adhesion to interleukin-1beta (IL
      beta)-stimulated human umbilical vein endothelial cells (HUVECs) were also
      examined. KEY RESULTS: Elastase release was inhibited by very low molecular
      weight fractions of heparin, with an apparent minimum chain length of 10
      saccharides required for full effect. In contrast, neutrophil-endothelial
      adhesion was unaffected by these fractionated heparins, suggesting that certain
      non-anticoagulant actions of heparin may be lost by such an approach. CONCLUSIONS
      AND IMPLICATIONS: These data suggest that an optimum chain length of heparin
      possibly exists for certain non-anticoagulant actions of heparin, which may prove
      to be useful in the design of novel drugs with specific anti-inflammatory
      actions.

PMID- 17533421
TI  - Combined pharmacological block of I(Kr) and I(Ks) increases short-term QT
      interval variability and provokes torsades de pointes.
AB  - BACKGROUND AND PURPOSE: Assessing the proarrhythmic potential of compounds during
      drug development is essential. However, reliable prediction of drug-induced
      torsades de pointes arrhythmia (TdP) remains elusive. Along with QT interval
      prolongation, assessment of the short-term variability of the QT interval
      (STV(QT)) may be a good predictor of TdP. We investigated the relative importance
      of I(Ks) and I(Kr) block in development of TdP together with correlations between
      QTc interval, QT interval variability and incidence of TdP. EXPERIMENTAL
      APPROACH: ECGs were recorded from conscious dogs and from anaesthetized rabbits
      given the I(Kr) blocker dofetilide (DOF), the I(Ks) blocker HMR-1556 (HMR) and
      their combination, intravenously. PQ, RR and QT intervals were measured and QTc
      and short-term variability of RR and QT intervals calculated. KEY RESULTS: DOF
      increased QTc interval by 20% in dogs and 8% in rabbits. HMR increased QTc in
      dogs by 12 and 1.9% in rabbits. Combination of DOF+HMR prolonged QTc by 33% in
      dogs, by 16% in rabbits. DOF or HMR given alone in dogs or HMR given alone in
      rabbits induced no TdP. Incidence of TdP increased after DOF+HMR combinations in
      dogs (63%) and following HMR+DOF (82%) and DOF+HMR combinations (71%) in rabbits.
      STV(QT) markedly increased only after administration of DOF+HMR combinations in
      both dogs and rabbits. CONCLUSION AND IMPLICATIONS: STV(QT) was markedly
      increased by combined pharmacological block of I(Kr) and I(Ks) and may be a
      better predictor of subsequent TdP development than the measurement of QTc
      interval prolongation.

PMID- 17533422
TI  - Achieving signalling selectivity of ligands for the corticotropin-releasing
      factor type 1 receptor by modifying the agonist's signalling domain.
AB  - BACKGROUND AND PURPOSE: Most of the pharmaceuticals target G-protein-coupled
      receptors (GPCRs) which can generally activate different signalling events. The
      aim of this study was to achieve functional selectivity of corticotropin
      releasing factor receptor type 1 (CRF(1)) ligands. EXPERIMENTAL APPROACH: We
      systematically substituted urocortin, a natural peptide agonist of CRF(1), with
      bulky amino acids (benzoyl-phenylalanine, naphthylalanine) and determined the
      effect of the analogues on coupling of CRF(1) to Gs- and Gi-protein in human
      embryonic kidney cells, using receptor binding, [(35)S]-GTPgammaS binding
      stimulation, and cAMP accumulation assays. KEY RESULTS: Native ligands stimulated
      Gs and Gi activation through CRF(1), resulting in stimulation and then inhibition
      of cAMP accumulation. Single replacements in urocortin at positions 6-15 led,
      dependent on the position and nature of the substituent, to ligands that
      conserved Gs activity, but were devoid of Gi activity, only stimulating cAMP
      accumulation, and competitively antagonized the Gi activation by sauvagine. In
      contrast, analogues with substitutions outside this sequence non-selectively
      activated Gs and Gi, as urocortin did. CONCLUSIONS AND IMPLICATIONS:
      Modifications in a specific region, which we have called the signalling domain,
      in the polypeptide agonist urocortin resulted in analogues that behaved as
      agonists and, at the same time, antagonists for the activation of different G
      proteins by CRF(1). This finding implies significant differences between active
      conformations of the receptor when coupled to different G-proteins. A similar
      structural encoding of signalling information in other polypeptide hormone
      receptor ligands would result in a general concept for the development of
      signalling-selective drug candidates.

PMID- 17533423
TI  - Characterization of spinal alpha-adrenergic modulation of nociceptive
      transmission and hyperalgesia throughout postnatal development in rats.
AB  - BACKGROUND AND PURPOSE: The selective alpha(2)-adrenergic agonist dexmedetomidine
      is used clinically for analgesia and sedation, but effects in early life are not
      well characterized. Investigation of age-related effects of dexmedetomidine is
      important for evaluating responses to exogenously administered analgesics and
      provides insight into postnatal function of noradrenergic pathways. EXPERIMENTAL
      APPROACH: We examined effects of epidural dexmedetomidine in anaesthetized rat
      pups (3, 10 and 21 postnatal days) using a quantitative model of nociception and
      C-fibre induced hyperalgesia. Electromyographic recordings of withdrawal
      responses to hindpaw mechanical stimuli measured effects of dexmedetomidine upon
      the baseline reflex and the response to mustard oil application on the hindpaw
      (primary hyperalgesia) or hindlimb (secondary hyperalgesia). In addition, we
      compared epidural with systemic administration, examined effects of spinal
      transection and evaluated heart rate changes following dexmedetomidine. KEY
      RESULTS: Epidural dexmedetomidine dose-dependently prevented mustard oil-induced
      hyperalgesia at all ages but dose requirements were lower in the youngest pups.
      Higher doses also suppressed the baseline nociceptive reflex when given
      epidurally, but had no effect when given systemically. Analgesic efficacy was the
      same for primary and secondary hyperalgesia, and was not diminished by spinal
      cord transection. CONCLUSIONS AND IMPLICATIONS: Our laboratory studies predict
      that spinally mediated alpha(2)-agonist analgesia would be effective throughout
      postnatal development, dose requirements would be lower in early life and
      selective anti-hyperalgesic effects could be achieved with epidural
      administration at doses lower than associated with antinociceptive or
      cardiovascular effects. Clinical trials of alpha(2) agonists in neonates and
      infants should consider developmentally regulated changes.

PMID- 17533424
TI  - Neuroprotection with or without erythropoiesis; sometimes less is more.
AB  - Erythropoietin (EPO) is a pleiotropic cytokine with a therapeutic potential that
      goes well beyond the treatment of anaemia. The study by Wang et al (2007b)
      examined the protective effects of EPO in a rat model of embolic stroke. The
      efficacy and haematological side effects of EPO were compared to those of a
      carbamylated EPO variant (CEPO). Treatment with EPO dose-dependently reduced
      infarct volume and improved long-term functional outcome. However, an increase in
      hematocrit was seen even for doses of EPO that did not offer neuroprotection.
      These data do not suggest the existence of a therapeutic window between effect
      and side effect for treatment with EPO. Treatment with CEPO was without
      haematological side effects.

PMID- 17533425
TI  - K+ channel modulation of slow wave activity in the guinea-pig prostate.
AB  - BACKGROUND AND PURPOSE: The aim of this study was to investigate the role of
      different K(+) channel populations and the inhibitory effect of various
      exogenously applied K(+) channel openers in the regulation of slow wave activity
      in the guinea-pig prostate. EXPERIMENTAL APPROACH: Recordings of membrane
      potential were made using intracellular microelectrodes. KEY RESULTS:
      Tetraethylammonium (TEA 300 micro M and 1 mM), iberiotoxin (150 nM) and 4
      aminopyridine (4-AP 1 mM) increased the frequency of slow wave discharge. Apamin
      (1-200 nM) and glibenclamide (1 micro M) had no effect on slow wave activity.
      Lemakalim (1 micro M) and PCO-400 (1 micro M) abolished the slow waves, as did
      sodium nitroprusside (SNP 10 micro M) and calcitonin gene-related peptide (CGRP
      100 nM). The inhibitory effect of these agents was independent of a significant
      change in membrane potential. In the presence of 4-AP (1 mM), TEA (1 mM) or
      glibenclamide (1 micro M) the inhibitory actions of SNP (10 micro M) were
      attenuated. The inhibitory actions of CGRP (100 nM) were also reversed by
      glibenclamide (1 micro M). In contrast, isoprenaline (1 micro M) did not alter
      the frequency of slow wave discharge. CONCLUSIONS AND IMPLICATIONS: These results
      demonstrate that BK(Ca) and 4-AP-sensitive K(+) channels regulate the frequency
      of prostatic slow wave discharge. SNP and CGRP abolish slow waves in a
      hyperpolarisation-independent manner, partially via opening of K(ATP) channels.
      BK(Ca) and 4-AP-sensitive K(+) channels also play an important role in the SNP
      induced inhibition of slow wave activity. The lack of membrane hyperpolarisation
      associated with the SNP- and CGRP-induced inhibition implies that the channels
      involved in this action are not predominantly located on the smooth muscle cells.

PMID- 17533426
TI  - Inhibition of acute nociceptive responses in rats after i.c.v. injection of Thr6
      bradykinin, isolated from the venom of the social wasp, Polybia occidentalis.
AB  - BACKGROUND AND PURPOSE: In this work, a neuroactive peptide from the venom of the
      neotropical wasp Polybia occidentalis was isolated and its anti-nociceptive
      effects were characterized in well-established pain induction models.
      EXPERIMENTAL APPROACH: Wasp venom was analysed by reverse-phase HPLC and
      fractions screened for anti-nociceptive activity. The structure of the most
      active fraction was identified by electron-spray mass spectrometry (ESI-MS/MS)
      and it was further assessed in two tests of anti-nociceptive activity in rats:
      the hot plate and tail flick tests. KEY RESULTS: The most active fraction
      contained a peptide whose structure was Arg-Pro-Pro-Gly-Phe-Thr-Pro-Phe-Arg-OH,
      which corresponds to that of Thr(6)-BK, a bradykinin analogue. This peptide was
      given by i.c.v. injection to rats. In the tail flick test, Thr(6)-BK induced anti
      nociceptive effects, approximately twice as potent as either morphine or
      bradykinin also given i.c.v. The anti-nociceptive activity of Thr(6)-BK peaked at
      30 min after injection and persisted for 2 h, longer than bradykinin. The primary
      mode of action of Thr(6)-BK involved the activation of B(2) bradykinin receptors,
      as anti-nociceptive effects of Thr(6)-BK were antagonized by a selective B(2)
      receptor antagonist. CONCLUSIONS AND IMPLICATIONS: Our data indicate that Thr(6)
      BK acts through B(2) bradykinin receptors in the mammalian CNS, evoking
      antinociceptive behaviour. This activity is remarkably different from that of
      bradykinin, despite the structural similarities between both peptides. In
      addition, due to the increased metabolic stability of Thr(6)-BK, relative to that
      of bradykinin, this peptide could provide a novel tool in the investigation of
      kinin pathways involved with pain.

PMID- 17533427
TI  - Taking the sting out of pain.
AB  - While the role of the brain kallikrein-kinin system in the development of various
      pathological processes, such as oedema formation following brain injury or
      induction of central hypertonia has generated major interest, the possible role
      of this system in nociceptive processing has received little attention. In their
      present paper, Mortari et al. (2007) show that bradykinin B2 receptor activation
      in the brain by the bradykinin analogue, Thr(6)-bradykinin, isolated from the
      venom of the social wasp, Polybia occidentalis potently reduces acute, noxious
      heat-evoked reflex responses in naive rats. The unknown underlying mechanism of
      this powerful antinociceptive effect reminds us that the supraspinal
      antinociceptive system is still a "black box" in many aspects and awaits thorough
      investigation.

PMID- 17533428
TI  - Different profiles of Ca2+ responses to endothelin-1 and PDGF in liver
      myofibroblasts during the process of cell differentiation.
AB  - BACKGROUND AND PURPOSE: Hepatic stellate cells play an important role in liver
      fibrosis but little is known about liver myofibroblasts located around the
      central vein and in the portal area. In this study, intracellular Ca(2+)
      concentration ([Ca(2+)](i)) was measured to assess the response to endothelin-1
      (ET-1), platelet derived growth factor (PDGF) and ATP in rat liver
      myofibroblasts. EXPERIMENTAL APPROACH: Rat liver myofibroblasts were compared in
      'quiescent' (cultured on Matrigel-coated dishes) and 'activated' (cultured on non
      coated plastic dishes) conditions. [Ca(2+)](i) was measured with the fluorescent
      dye fura-2 and mRNA for ET-1, PDGF and their receptors by RT-PCR. KEY RESULTS: ET
      1 increased [Ca(2+)](i) in quiescent cells but not in activated cells, whereas
      PDGF-BB increased [Ca(2+)](i) in activated cells but not in quiescent cells.
      However, there was no difference between responses to ATP in quiescent or
      activated cells. ET-1 (in quiescent cells), PDGF-BB (in activated cells) and ATP
      (in both cells) all induced transient increases in [Ca(2+)](i) in the absence of
      extracellular Ca(2+) (with EGTA), indicating the involvement of Ca(2+) release
      from intracellular Ca(2+) stores. The sustained increase in [Ca(2+)](i) in the
      presence of external Ca(2+) in activated cells (ATP and PDGF) was significantly
      reduced by nicardipine, a L-type Ca(2+) channel blocker, but not in quiescent
      cells (ATP and ET-1). CONCLUSIONS AND IMPLICATIONS: The different pharmacological
      profiles of [Ca(2+)](i)-response in quiescent and activated myofibroblasts
      suggest that ET-1 and PDGF contribute differently to myofibroblast activation
      during the process of liver fibrosis.

PMID- 17533430
TI  - Students perceptions of the incorporation of games into classroom instruction for
      basic and clinical pharmacokinetics.
AB  - OBJECTIVE: To develop classroom games as alternatives to traditional
      pharmacokinetic instruction. DESIGN: three classroom games were created for the
      following purposes: simple semester review, application of pharmacokinetics in a
      community-pharmacy setting, and development of critical thinking skills and
      concept application. All the games incorporated some degree of group activity.
      ASSESSMENT: A survey was conducted of students' attitudes towards the
      incorporation of games into the classroom. A comparison of final examination
      scores to scores from the previous year was used to determine whether
      incorporating games hindered learning. CONCLUSIONS: Overall, students found the
      games enjoyable, but some students questioned how much they learned. Although the
      games appeared to have a positive impact on grades and incorporated more than
      just factual, book knowledge (eg, critical thinking skills), determining how
      these games improved learning will require further assessment.

PMID- 17533431
TI  - Pharmacy student focus groups for formative evaluation of the learning
      environment.
AB  - OBJECTIVE: To develop a student focus group process for formative evaluation of
      the learning environment in a college of pharmacy. DESIGN: Student focus groups
      were formed and met from fall 2002 to spring 2006. During spring 2005, student
      cohorts (first- through third-professional years) were surveyed and anecdotal
      evidence about the process was gathered from faculty members. ASSESSMENT: Student
      opinions about the effectiveness of the focus groups were fairly positive, with
      59% to 87% agreeing that the process allowed students to communicate effectively
      with faculty members. The main problems identified were lack of communication
      between focus group members and the student body, and the lack of response by
      some faculty members to student concerns. Based on anecdotal evidence, faculty
      members agreed that the process encouraged student development but was less
      useful for pedagogical issues. CONCLUSION: Focus groups can be an effective way
      of providing feedback to faculty members and students about the classroom
      learning environment if students are trained to give appropriate feedback and
      professors are supported in responding to student input.

PMID- 17533429
TI  - Curriculum mapping in program assessment and evaluation.
AB  - OBJECTIVES: To demonstrate a curriculum mapping technique and its use in program
      evaluation and assessment, as well as to provide specific recommendations for
      potential uses in pharmacy education. METHODS: This study employed a descriptive
      cross-sectional study design based on a learning outcomes document and several
      existing student and curricular data sets. RESULTS: The population consisted of
      209 PharmD students at the University of Arizona College of Pharmacy (UACOP)
      during the 2004-2005 academic year and mapped 31 of the 34 required didactic
      courses in the curriculum. There was concordance between student and faculty
      member ranking of domain coverage in their respective curricular maps.
      CONCLUSIONS: The agreement between the student and faculty graphical curriculum
      maps on the order of the ranking of the relative emphasis of each domain suggests
      concordance between the intended/delivered and received curriculums. This study
      demonstrated a curriculum mapping methodology that can be used to both make sense
      and use of existing data in curricular evaluation.

PMID- 17533432
TI  - A project management approach to an ACPE accreditation self-study.
AB  - In preparation for an on-site evaluation and accreditation by the American
      Council on Pharmaceutical Education (ACPE), the Albany College of Pharmacy
      employed project management techniques to complete a comprehensive self-study. A
      project lifecycle approach, including planning, production, and turnover phases,
      was used by the project's Self-Study Steering Committee. This approach, with
      minimal disruption to college operations, resulted in the completion of the self
      study process on schedule. Throughout the project, the Steering Committee
      maintained a log of functions that either were executed successfully or in
      hindsight, could have been improved. To assess the effectiveness of the project
      management approach to the the self-study process, feedback was obtained from the
      College community through a poststudy survey. This feedback, coupled with the
      Steering Committee's data on possible improvements, form the basis for the
      lessons learned during this self-study process.

PMID- 17533433
TI  - Assessing implementation of cultural competency content in the curricula of
      colleges of pharmacy in the United States and Canada.
AB  - OBJECTIVES: To assess the presence of curricular and organizational content
      related to cultural competency within colleges of pharmacy in the United States
      and Canada. METHODS: Curriculum committee chairs (n = 87) and student leaders (n
      = 54) in colleges of pharmacy in the United States and Canada were surveyed via
      an e-mailed assessment tool. RESULTS: Forty-nine (56.3%) curriculum committee
      chairs and 27 (50%) student leaders returned usable responses. Respondents
      reported that cultural competency was mentioned in 61.2% of their mission
      statements, and half had made curricular changes with respect to diversity within
      the past 5 years. Almost 94% felt the necessity to add cultural competency topics
      to required courses in the curriculum, and 42.9% wanted to add a course specific
      to cultural competency into the curriculum. CONCLUSION: Curriculum committee
      chairs recognize the need to add curricular content related to cultural
      competency, but not all of the respondents have implemented changes in their
      college's curriculum.

PMID- 17533434
TI  - Preparing students for community pharmacy practice during a drug information
      advanced practice experience.
AB  - OBJECTIVE: To determine whether students completing an advanced pharmacy practice
      experience (APPE) at an academic-affiliated drug information center received
      questions similar to those received by pharmacists practicing in community
      settings. METHODS: Graduates of Samford University McWhorter School of Pharmacy
      residing in Southeastern states were surveyed via US mail to determine the
      characteristics of inquiries received from health care providers and the public
      in community practice. Survey results were compared to inquiries received at
      Samford University Global Drug Information Center (SUGDIS). RESULTS: The response
      rate to the survey of graduates was 36% (268 of 738 surveys). Respondents
      identified nonprescription drugs (65%), adverse drug reactions (62.7%), and drug
      interactions (62.4%) as the top 3 types of questions answered routinely in
      community practice, while drug therapy (13.9%), dosing (10.2%), and adverse drug
      reactions (6.5%) were the 3 types of questions most commonly answered at SUGDIS.
      The most common resources used to answer questions in the community and SUGDIS
      were Drug Facts and Comparisons and specialty references, respectively.
      CONCLUSIONS: Differences were noted in types of questions received, expected
      speed of response, and reference utilization. As a result, activities were
      incorporated into the drug information APPE to address the disparities noted in
      the study.

PMID- 17533435
TI  - The need to invest in community pharmacy practice.

PMID- 17533436
TI  - Rethinking experiential education (or does anyone want a pharmacy student?).

PMID- 17533437
TI  - Using the humanities to strengthen the concept of professionalism among first
      professional year pharmacy students.
AB  - OBJECTIVES: To engage pharmacy students at the McWhorter School of Pharmacy in an
      authentic discussion of professionalism early in their education. METHODS: A
      booklet was prepared that included several classic short stories and essays that
      dealt with professionalism. This booklet was sent to all entering students in the
      class of 2008 and 2009 during the summer prior to their first-professional year
      of the PharmD program. The stories and essays were discussed in small groups with
      faculty facilitation during orientation when the students first arrived on
      campus. A survey instrument was created and administered to assess the impact of
      this innovative approach to enhancing professionalism. RESULTS: The program was
      well received and engaged our pharmacy students in a productive discussion on
      professionalism. Both classes' mean scores on survey items related that the
      students were engaged in the discussion of professionalism. Survey results
      pertaining to professional behavior also indicated increased awareness of the
      importance of professionalism. CONCLUSION: Enhancing professionalism requires a
      culture change that necessitates addressing professionalism at its core, a
      calling to serve, in a persistent and continual manner. Requiring students to
      read and think about professionalism in a novel way, before they even begin their
      first-professional year of pharmacy school, appears to be an effective approach
      to nurturing/encouraging professionalism.

PMID- 17533438
TI  - Community-based collaboration with high school theater students as standardized
      patients.
AB  - OBJECTIVES: To describe a collaborative undertaking between a private school of
      pharmacy (Bernard J. Dunn School of Pharmacy) and a public high school (John
      Handley High School) in the development, and implementation of a partnership
      utilizing high school theater students as standardized patients. METHODS: High
      school theater students were trained to portray patients within the Standardized
      Patient Assessment Laboratory. The patient encounters were videotaped and
      evaluated by both peer and faculty members. Quantitative and qualitative analyses
      of semi-structured interviews, focus groups, post-encounter surveys of students
      and faculty members, and encounter grades were used to evaluate the outcomes.
      RESULTS: Pharmacy students exhibited competence in clinical assessment skills as
      evidenced by high encounter grades (91.5% +/- 6.8%) and 100% positive faculty
      feedback. The high school theater students self-reported that their
      improvisational skills improved through learning patient conditions and
      behaviors. Both schools met their mission statement and accreditation goals,
      including increased collaboration with the community. CONCLUSION: This model for
      collaboration between a school of pharmacy and a high school using adolescents as
      simulated patients was successful in creating a beneficial learning experience
      for both the theater and pharmacy students.

PMID- 17533439
TI  - Integrating virtual patients into a self-care course.
AB  - OBJECTIVE: To develop, implement, and evaluate the use of virtual patients as a
      teaching tool for third-professional year PharmD students within an advanced
      elective self-care course. DESIGN: Practicing community pharmacists, faculty
      members, and pharmacy residents with alias e-mail accounts served as virtual
      patients and corresponded on a weekly basis via e-mail with pharmacy students
      regarding an assortment of fictional health concerns. Self-care inquiries were e
      mailed to the students who replied and then forwarded their response to the
      course coordinator for evaluation and class discussion. At the end of the course,
      students were asked to assess the value of the learning activity. ASSESSMENT:
      Students demonstrated significant improvement in knowledge, problem-solving,
      communication, and professional skills upon course completion. Student's
      assessments of the virtual patient activity have suggested positive feedback on
      developing self-care skills, patient interactions, and group dynamics.
      CONCLUSION: This teaching tool was designed to enhance student's knowledge base,
      assessment, and counseling skills when interacting with patients in various
      situations. Instructor evaluation of responses, student feedback, and self
      evaluation indicated the activity improved overall knowledge and communication
      skills.

PMID- 17533440
TI  - Professionalism: a determining factor in experiential learning.
AB  - The University of Maryland School of Pharmacy has systematically implemented
      professionalism assessment to establish expectations in experiential learning and
      to create a mechanism for holding students accountable for professionalism. The
      authors describe their philosophic approach to the development and implementation
      of these explicit criteria and also review the outcomes of applying these
      criteria. In 2001, 3 professionalism criteria were developed and applied to
      required intermediate and advanced pharmacy practice experiences (APPEs).
      Students were expected to achieve 100% acceptable ratings to pass the rotations.
      The criteria were subsequently enhanced and by 2005 applied to all experiential
      courses. Most students exhibited professional behavior; however, 9 students did
      not meet the established criteria. Strategies used in remediation and further
      professional development are discussed. The use of professionalism criteria has
      promoted a culture of professionalism throughout the School.

PMID- 17533441
TI  - A model for supporting and training clinical pharmaceutical scientist PhD
      students.
AB  - OBJECTIVES: To enhance the clinical training and financial support of graduate
      students in a Clinical Pharmaceutical Scientist PhD Program at the University of
      Pittsburgh School of Pharmacy. DESIGN: The School of Pharmacy and University of
      Pittsburgh Medical Center entered into a collaborative agreement to develop the
      Clinical Scientist Associate (CSA) program, as well as financially support
      students enrolled in a Pharmaceutical Sciences PhD program. These clinical
      training experiences are in addition to the didactic and laboratory experiences
      in the pharmaceutical sciences graduate program. ASSESSMENT: Since 2002, three
      students have participated as CSAs, simultaneously working on their graduate
      research and meeting the requirements of the CSA program. CONCLUSIONS: The CSA
      program is a novel model for clinical training and support of post-PharmD
      graduate students enrolled in a PhD clinical pharmaceutical scientist program.

PMID- 17533442
TI  - Providing formative feedback from a summative computer-aided assessment.
AB  - OBJECTIVES: To examine the effectiveness of providing formative feedback for
      summative computer-aided assessment. DESIGN: Two groups of first-year
      undergraduate life science students in pharmacy and neuroscience who were
      studying an e-learning package in a common pharmacology module were presented
      with a computer-based summative assessment. A sheet with individualized feedback
      derived from each of the 5 results sections of the assessment was provided to
      each student. Students were asked via a questionnaire to evaluate the form and
      method of feedback. ASSESSMENT: The students were able to reflect on their
      performance and use the feedback provided to guide their future study or
      revision. There was no significant difference between the responses from pharmacy
      and neuroscience students. Students' responses on the questionnaire indicated a
      generally positive reaction to this form of feedback. CONCLUSIONS: Findings
      suggest that additional formative assessment conveyed by this style and method
      would be appreciated and valued by students.

PMID- 17533444
TI  - Development of an office of teaching, learning and assessment in a pharmacy
      school.
AB  - This article describes the background, development, and assessment of an Office
      of Teaching, Learning and Assessment at the Harrison School of Pharmacy, Auburn
      University. This case study is intended to provide other colleges and schools
      with insights that may facilitate the relatively unproblematic development of
      similar programs.

PMID- 17533443
TI  - Use of reflective portfolios in health sciences education.
AB  - Reflective portfolios are a collection of evidence that through critical
      reflection on its contents demonstrate achievement as well as personal and
      professional development. The purpose of this paper is to provide a review of the
      literature on the use of reflective portfolios and to develop a set of factors to
      guide schools and colleges of pharmacy as they implement reflective portfolios
      into their respective curricula as stated in Standards 2007.

PMID- 17533445
TI  - A communication course for a linguistically diverse student population.
AB  - OBJECTIVES: To establish an elective course designed to improve oral
      communication skills of students whose first or best language or dialect is not
      North American English. DESIGN: A course that combined English as a Second
      Language pedagogy with pharmacy applications and content was created. Class
      exercises on language skills in pharmacy-specific content areas were conducted.
      Course evaluations were administered at the end of each course offering.
      ASSESSMENT: The majority of students in the 11 sections who completed Oral
      Communication in Health Care improved their oral skills sufficiently to pass the
      exit examination and clinical courses requiring oral proficiency. Course
      evaluation forms show that students found this course useful, including the 15
      students who took the course in fall 2005, described here. CONCLUSION: An oral
      communication course targeted to students enrolled in a doctor of pharmacy or
      pharmaceutical sciences degree program whose first or best language was not
      English resulted in improved mastery of course outcomes and thus improved oral
      communication skills. As with any language acquisition process, continued
      practice is required to maintain proficiency.

PMID- 17533447
TI  - India to introduce five-year doctor of pharmacy program.

PMID- 17533448
TI  - Science-based pharmacy education.

PMID- 17533450
TI  - Single molecule biology: coming of age.
AB  - Cellular heterogeneity and stochastic fluctuation play key roles in biological
      processes. Single molecule approaches have the key advantage of avoiding ensemble
      averaging, allowing the observation of transient intermediates and heterogeneity
      (both static and dynamic). Thus they have revolutionised the way many biological
      questions are addressed. The challenge ahead is to develop integrated approaches
      such as the combination of single molecule imaging with single molecule
      manipulation to probe the dynamics of gene regulatory and cell signalling
      networks in living cells.

PMID- 17533451
TI  - Imaging proteins in vivo using fluorescence lifetime microscopy.
AB  - Fluorescence lifetime imaging (FLIM) represents a key optical technique for
      imaging proteins and protein interaction in vivo. We review the principles and
      recent advances in the application of the technique, instrumentation and
      molecular probe development.

PMID- 17533452
TI  - Tagged library approach facilitates forward chemical genetics.
AB  - Forward chemical genetics has been highlighted as a new method for the study of
      various biological pathways using exogenous ligands. However, limited success in
      the field has demonstrated that, in many cases, it is not feasible to determine
      the protein targets of small-molecule probes. Identifying protein targets is an
      integral part of forward chemical genetics and is also the most challenging. Over
      the past decade, several biochemical and genetic methods have been developed to
      facilitate target identification processes. Even so, one of the major
      difficulties is that these methods require the chemical modification of active
      compounds, with a significant amount of structure-activity relationship (SAR)
      study to ensure that the small-molecule tags do not compromise bioactivity. In
      this article, we will highlight a new strategy for small molecule libraries that
      have built-in linkers in order to avoid this well-known problem and demonstrate
      their successful use in forward chemical genetics.

PMID- 17533453
TI  - Methods to probe protein transitions with ATR infrared spectroscopy.
AB  - We describe techniques that can be used in conjunction with modern attenuated
      total reflection (ATR) infrared micro-prisms to allow proteins to be manipulated
      cyclically between different states whilst simultaneously monitoring both mid-IR
      and UV/visible/near IR changes. These methods provide increased flexibility of
      the types of changes that can be induced in proteins in comparison to
      transmission methods. Quantitative measurements can be made of vibrational
      changes associated with conversion between stable catalytic reaction
      intermediates, ligand binding and oxidation-reduction. Both hydrophobic and
      soluble proteins can be analysed and the ability to induce transitions
      repetitively allows IR difference spectra to be acquired at a signal/noise
      sufficient to resolve changes due to specific cofactors or amino acids. Such
      spectra can often be interpreted at the atomic level by standard IR methods of
      comparisons with model compounds, by isotope and mutation effects and,
      increasingly, by ab initio simulations. Combination of such analyses with atomic
      3D structural models derived from X-ray and NMR studies can lead to a deeper
      understanding of molecular mechanisms of enzymatic reactions.

PMID- 17533454
TI  - Novel tRNA aminoacylation mechanisms.
AB  - In nature, ribosomally synthesized proteins can contain at least 22 different
      amino acids: the 20 common amino acids as well as selenocysteine and pyrrolysine.
      Each of these amino acids is inserted into proteins codon-specifically via an
      aminoacyl-transfer RNA (aa-tRNA). In most cases, these aa-tRNAs are
      biosynthesized directly by a set of highly specific and accurate aminoacyl-tRNA
      synthetases (aaRSs). However, in some cases aaRSs with relaxed or novel substrate
      specificities cooperate with other enzymes to generate specific canonical and non
      canonical aminoacyl-tRNAs.

PMID- 17533455
TI  - Synthesis, patterning and applications of star-shaped poly(ethylene glycol)
      biofunctionalized surfaces.
AB  - Poly(ethylene) glycol (PEG) is an excellent material to modify surfaces to resist
      non-specific protein adsorption. Linear PEG has been extensively studied both
      theoretically and experimentally and it has been found that resistance of PEG
      coated surfaces to protein adsorption depends mainly on the molecular weight of
      the polymer and the surface grafting density. End-functionalized star-shaped PEGs
      allow for interpolymer crosslinking to form a dense layer. An excellent example
      of such a system consists of a 6-arm PEG/PPG (4 : 1) star polymer functionalized
      with isocyanate using IPDI. The end functionalization may be further
      biofunctionalized to recognize specific biomolecules such as streptavidin, His
      tagged proteins, amino-terminated oligonucleotides and cell receptors. This
      functionalization may be patterned into specific geometries using stamping
      techniques or randomly distributed by statistical reaction of the end group with
      the biofunctional molecule in solution. The surface preparation uses simple spin
      , dip- or spray-coating and produces smooth layers with low background
      fluorescence. These properties, together with the advantageous chemical
      properties of PEG, render the surfaces ideal for immobilizing proteins on
      surfaces with detection limits down to the single molecule level. Proteins
      immobilized on such surfaces are able to maintain their folded, functional form
      and are able to completely refold if temporarily exposed to denaturing
      conditions. Immobilized enzyme molecules were able to perform their function with
      the same activity as the enzyme in solution. Future directions of using surfaces
      coated with such crosslinked star polymers in highly sensitive and robust
      biotechnology applications will be discussed.

PMID- 17533456
TI  - A novel chemiluminescent substrate for detecting lactamase.
AB  - Beta-lactamase is a well established reporter for monitoring cellular events
      while chemiluminescence is the preferred read-out mode in high throughput
      screens. Here, we report the first chemiluminescent assay for beta-lactamase
      using beta-galactosidase based enzyme fragment complementation technology. The
      enzyme fragment complementation technology employs a large protein fragment
      called the enzyme acceptor and a small peptidic fragment called an enzyme donor.
      These fragments are inactive separately but recombine rapidly in solution to
      yield active beta-galactosidase detected by chemiluminescence or fluorescence. A
      cyclic enzyme donor comprising a substituted cephalosporin moiety is used as the
      lactamase substrate. The cyclic substrate does not complement with enzyme
      acceptor to yield active beta-galactosidase, but upon cleavage with lactamase
      yields the linear enzyme donor which complements readily with enzyme acceptor.
      This methodology has been exploited in a simple, sensitive, homogeneous cell
      based reporter gene assay to monitor G-protein coupled receptor activation in a
      microtitre plate with a chemiluminescent read out.

PMID- 17533457
TI  - Endoprosthesis implantation at the entry pathway of the right atrium monitored by
      intracardiac ultrasound.
AB  - Obstructions of the upper venous system may be due to spontaneous thrombosis or
      the presence of hemodialysis or chemotherapy catheters, or even the presence of
      extrinsic compression due to intra-thoracic tumors. The use of endoprosthesis for
      the treatment of these obstructions has become common practice, and its
      indications include situations of risk for pulmonary embolism, superior vena cava
      syndrome, and loss of vascular access. Within this context, the use of
      intracardiac ultrasound may be useful in evaluating the extension and severity of
      the obstructive lesion, besides providing important information about the mural
      and intraluminal morphology of the venous system. The authors report the case of
      a patient with superior vena cava syndrome caused by thrombosis at the entry
      pathway of the right atrium, besides discussing the subject by means of
      literature review.

PMID- 17533458
TI  - Percutaneous coronary intervention in single coronary artery in a patient with
      high-risk unstable angina.
AB  - In the present case, we report the performance of coronary angioplasty with stent
      implantation in the right coronary artery of a patient with high-risk unstable
      angina and single coronary artery originating from the right coronary sinus. The
      anterior descending and circumflex arteries originated separately from the
      proximal third of the right coronary artery. This is a rare coronary anomaly and
      few reports of percutaneous coronary intervention are found in the literature.
      This case illustrates the need for a detailed anatomical assessment of the course
      of the coronary arteries prior to the performance of a percutaneous transluminal
      angioplasty, with the purpose of preventing complications.

PMID- 17533459
TI  - Clinical follow-up of a pregnant woman with cor triatriatum.
AB  - Cor triatriatum (CT) is a rare congenital cardiac anomaly that usually becomes
      symptomatic in the first years of life. If the condition is not associated with
      other cardiac defects, and depending on the degree of communication between the
      upper chamber and left atrium (LA), patients may reach adulthood. We report a
      case of an asymptomatic, adult, female patient with CT diagnosed by transthoracic
      echocardiogram (TTE) and followed-up during pregnancy.

PMID- 17533460
TI  - Transhepatic access for atrioseptostomy in a neonate.
AB  - We report a case in which a neonate with complete transposition of the great
      arteries was submitted to an atrial septostomy through transhepatic access due to
      congenital interruption of the inferior vena cava. The technical aspects of the
      procedure are discussed.

PMID- 17533461
TI  - Percutaneous mitral valvuloplastry in a pregnant woman guided only by the
      transesophageal echocardiography.
AB  - Mitral valve stenosis is the most common valve lesion in pregnancy. In spite of
      an optimized clinical treatment and a favorable valve anatomy according to
      Wilkins and Block score, in symptomatic patients, percutaneous intervention is
      shown to be of great importance. In these patients, avoiding x-ray exposure as
      much as possible is recommended so as to protect the fetus from the deleterious
      effects of ionizing radiation. In this case report, a 24-year old pregnant
      patient with severe mitral stenosis (valve area of 0.9 cm(2)) was successfully
      submitted to a TEE-guided percutaneous treatment, without the use of x-ray.

PMID- 17533462
TI  - Traumatic fistula between the right coronary artery and right atrial chamber.

PMID- 17533463
TI  - Treatment of Cheyne-Stokes respiration in patients with congestive heart failure.

PMID- 17533464
TI  - Ventricular electrical activation in cardiac resynchronization as characterized
      by body surface potential mapping.
AB  - OBJECTIVES: To assess cardiac electrical activation by using body surface
      potential mapping (BSPM), in patients with congestive heart failure (CHF) and
      left bundle branch block (LBBB) undergoing cardiac resynchronization therapy
      (CRT) with biventricular pacemaker (BIV-PM) implantation. METHODS: Mean cardiac
      electrical activation times were analyzed in the right ventricle (RV) (mean RV
      activation time = mRV), anteroseptal area (mAS), and left ventricle (mLV) of 28
      patients (mean age 61.2 +/- 9.5 years; NYHA class III-IV CHF; ejection fraction
      <40%; LBBB of mean QRS 181.2+/-19.4 ms, SAQRS -8.5 masculine+/-68.6 masculine),
      as shown in their BSPM isochronous maps, before and after implantation of
      atriobiventricular pacemaker, comparing those with values obtained from a control
      group of normal individuals [CG], in three situations: (1) native LBBB; (2) RV
      pacing; and (3) atriobiventricular pacing. RESULTS: Situation (1): mRV and mAS
      values were similar (41.0+/-11.8 ms x 43.6+/-13.4 ms), with delayed mLV (81.0+/
      12.5 ms, p<0.01) and asynchronous with RV and AS areas; situation (2): mRV was
      greater than in CG (86.8+/-22.9 ms, p<0.001), with greater difference between mAS
      and mLV (63.4+/-20.7 ms vs. 102.7+/-20.3 ms; p<0,001); situation (3): mLV and mRV
      were similar (72.0+/-32.0 ms vs. 71.6+/-32.3 ms), mRV was greater than in CG and
      native LBBB (71.6+/-32.3 ms vs. 35.1+/-10.9 ms and 41.0+/-11.8 ms; p<0.001), and
      mAS was close to CG and native LBBB values (51.3+/-32.8 ms vs. 50.1+/-11.4 ms and
      43.6+/-13.4 ms). CONCLUSION: The body surface potential mapping showed that RV
      and LV activation times which are similar, and are close to those of the AS area,
      suggest patterns of synchronized ventricular activation in patients with CHF and
      LBBB during atriobiventricular pacing.

PMID- 17533465
TI  - Incidence of shock and quality of life in young patients with implantable
      cardioverter-defibrillator.
AB  - OBJECTIVES: To analyze the incidence and causes of ICD therapies in children and
      young adults and verify their impact on the quality of life (QoL). METHODS: From
      March/1977 to February/2006, 29 patients (15.7+/-5.4 years old) were submitted to
      ICD implants. Aborted cardiac arrest (41.5%), sustained ventricular tachycardia
      (27.6%) and primary prophylaxis of sudden cardiac death (30.9%) indicated device
      therapy. The number of therapies was evaluated by interviewing patients and by
      ICD diagnostic data. The SF-36 questionnaire was used to measure the QoL and the
      results were compared to healthy population. The expectative of freedom from ICD
      therapies were estimated by the Kaplan-Meier method. RESULTS: After 2.6+/-1.8
      years follow-up, 8 (27.6%) patients received 141 appropriate ICD shocks due to
      ventricular tachycardia (6) or ventricular fibrillation (2), and 11 (37.9%)
      patients received 152 inappropriate ICD shocks due to supraventricular
      tachyarrhythmias (8) or oversensing (3). Expectative of freedom from appropriate
      shocks was 74.2+/-9.0% and 66.7+/-10.7% after one and three years, respectively.
      Compared to healthy population, QoL decreased in physical function (61.7+/-28.7),
      vitality (64.7+/-19.1), mental health (65.9+/-22.7) and role-emotional domains
      (66.7+/-38.5). All patients referred fear and concern related to ICD use.
      CONCLUSION: Despite the efficacy of ICD therapies, the high incidence of
      appropriate and inappropriate shocks interfered in patients QoL and adaptation to
      the device.

PMID- 17533466
TI  - Radiofrequency catheter ablation of premature ventricular contractions
      originating in the right ventricular outflow tract.
AB  - OBJECTIVES: To evaluate if radiofrequency catheter ablation is an effective
      procedure for the treatment of right ventricular outflow tract premature
      ventricular contractions (RVOT-PVC) and ascertain if it results in an improvement
      of symptoms. METHODS: A prospective study with 30 consecutive patients (mean age
      40 +/- 13 years, 25 females), with no apparent structural cardiopathy, with very
      frequent (mean density of 1,263 +/- 593/h) RVOT-PVC, symptomatic for more than
      one year (mean = 74 months) and resistant to antiarrhythmic drugs (3 +/- 1.7,
      including beta-blockers), who underwent radiofrequency catheter ablation.
      RESULTS: After the first procedure, there were 23 initial successful cases
      (76.6%) and 7 initial failures (23.4%). Four patients experienced relapses, two
      of whom did not undergo the second procedure. The second procedure was carried
      out in 9 patients (7 initial failures and 2 relapses), and there was success in 5
      additional patients, one of them by epicardial access. The final success rate was
      80% (24/30), and there were no major complications. After a mean follow-up of 14
      +/- 6 months, in the successful group there was a reduction greater than 90% in
      density of premature ventricular contractions (PVC) (24/24; p<0.0001) and a
      resulting absence of symptoms in the majority of patients (23/24; p<0.001).
      CONCLUSION: Radiofrequency catheter ablation is a safe and effective treatment
      for patients with persistent and symptomatic PVC with RVOT morphology.

PMID- 17533467
TI  - Ablation of typical atrial flutter: a prospective randomized study of cooled-tip
      versus 8-mm-tip catheters.
AB  - OBJECTIVES: Both ablation catheters with closed irrigated system and 8mm tip
      catheters have been shown to be more effective for typical atrial flutter
      radiofrequency (RF) ablation when compared to conventional 4 mm tip catheter.
      Considering the differences in complexity and costs of both systems, a
      prospective study was designed to compare the efficacy and safety of cooled-tip
      and 8mm-tip catheters for atrial flutter ablation. METHODS: Fifty-two consecutive
      patients underwent RF ablation of cavotricupsid isthmus (CTI) for the treatment
      of typical atrial flutter, using catheter with closed irrigation system (n=26) or
      8 mm-tip catheter (n=26). The RF pulses were applied point-by-point for 60
      seconds, with power limited at 50 w for the irrigated catheter and by temperature
      control (60 degrees/70 w) for the 8 mm catheter. RESULTS: The CTI block was
      successfully performed in 98.1%. Four patients in the irrigated group needed to
      switch to the other group. There was no significant difference with regard to
      ablation parameters, such as total time of RF ablation (591.1+/-309.0 s vs
      486.2+/-250.8 s), total procedure duration (86.4+/-23.6 vs 78.1+/-22.5 min) and
      time of fluoroscopy (17.0+/-6.7 vs 15.4+/-4.6 min). During follow-up of 10.6
      months in average, one patient in the irrigated group had recurrence of typical
      atrial flutter. CONCLUSION: Efficacy and safety of CTI ablation was comparable
      between both techniques (irrigated catheter and 8 mm-tip catheter). The
      complexity of irrigated catheter makes it less competitive.

PMID- 17533468
TI  - Treatment of massive pulmonary embolism by percutaneous fragmentation of the
      thrombus.
AB  - OBJECTIVES: To evaluate the safety and efficacy of percutaneous thrombus
      fragmentation (PTF) for massive pulmonary embolism (PE) in patients with
      contraindications to the administration of thrombolytics. METHODS: Between July
      1999 and August 2005, 10 patients (7 males, 3 females, age 57+/-18 years) with
      massive PE and contraindications to the administration of thrombolytics underwent
      PTF. A transthoracic doppler echocardiogram was used to evaluate arterial oxygen
      saturation (Sat O2), the Walsh index (WI), mean pulmonary artery pressure (PAP),
      mean systemic blood pressure (SBP) and right ventricular function (RVF) before
      and after the procedure. Statistical analysis was conducted using the paired
      Wilcoxon test, of which p was significant when < 0.05. RESULTS: After the PTF
      treatment there was an improvement in Sat. O2 [87.4 +/- 1.3% vs 92.3 +/- 3.1% (p
      < 0.001)], WI [6.4 +/- 1.07 vs 4.4 +/- 1.42 (p = 0.003)], PAP [31.8 +/- 4.6 mmHg
      vs 25.5 +/- 3.4 mmHg (p < 0.001)] and SBP [73.9 +/- 8.7 vs 85 +/- 8.3 (p =
      0.001). The ten patients had severe RVF before the percutaneous treatment;
      however, within 10 days after PTF, 8 presented normal or discrete function and 1
      presented mitigated function. There were no technical or vascular access site
      complications related to PTF. One patient died in the hospital (10%). The
      procedure was successful for the other nine patients. CONCLUSION: The lack of
      adverse complications related to the procedure, proves that PTF is safe. The
      improvement in Sat O2, WI, PAP, SBP and RVF in 90% of the cases demonstrates the
      efficacy of the procedure, indicating that it is an alternative treatment for
      massive PE in patients with contraindications for the administration of systemic
      thrombolytics.

PMID- 17533469
TI  - Gender differences in ventricular volumes and left ventricle ejection fraction
      estimated by myocardial perfusion imaging: comparison of Quantitative Gated SPECT
      (QGS) and Segami software programs.
AB  - OBJECTIVES: To test for gender differences in the measurements obtained by Segami
      and Quantitative Gated SPECT (QGS) software programs. METHODS: 181 asymptomatic
      individuals without heart disease were submitted to myocardial perfusion imaging.
      End-diastolic volumes (EDV), end-systolic volumes (ESV) and left ventricular
      ejection fraction (LVEF) were measured by QGS and Segami software programs to
      evaluate the influence of gender, age, weight, height, heart rate, systolic blood
      pressure, diastolic blood pressure, body mass index and body surface area.
      RESULTS: The means in the QGS method were: EDV (women= 68 ml; men= 95 ml;
      p<0.001), LVEF (women= 66.24%; men= 58, 7%) and Segami: EDV (women= 137 ml; men=
      174 ml), LVEF (women= 62.67%; men= 58, 52%). There were significant differences
      between men and women in the EDV (p<0.001), ESV (p<0.001) and LVEF (p=0.001) that
      persisted after adjusting for body surface area. CONCLUSION: Ventricular volumes
      were significantly lower and LVEF was significantly higher in women, estimated by
      QGS or Segami software programs.

PMID- 17533470
TI  - Ischemic preconditioning and spinal cord function monitoring in the descending
      thoracic aorta approach.
AB  - OBJECTIVES: To evaluate the effectiveness of acute ischemic preconditioning (IP),
      based on somatosensory evoked potentials (SSEP) monitoring, as a method of spinal
      cord protection and to asses SSEP importance in spinal cord neuromonitoring.
      METHODS: Twenty-eight dogs were submitted to spinal cord ischemic injury attained
      by descending thoracic aorta cross-clamping. In the C45 group, the aortic cross
      clamping time was 45 min (n=7); in the IP45 group, the dogs were submitted to IP
      before the aortic cross-clamping for 45 min (n=7). In the C60 group, the dogs
      were submitted to 60 min of aortic cross-clamping (n=7), as in the IP60 group
      that was previously submitted to IP. The IP cycles were determined based on SSEP
      changes. RESULTS: Tarlov scores of the IP groups were significantly better than
      those of the controls (p = 0.005). Paraplegia was observed in 3 dogs from C45 and
      in 6 from C60 group, although all dogs from IP45 group were neurologically
      normal, as 4 dogs from IP60. There was a significant correlation between SSEP
      recovery time until one hour of aortic reperfusion and the neurological status (p
      = 0.011), showing sensitivity of 75% and specificity of 83%. CONCLUSION:
      Repetitive acute IP based on SSEP is a protection factor during spinal cord
      ischemia, decreasing paraplegia incidence. SSEP monitoring seems to be a good
      neurological injury assessment method during surgical procedures that involve
      spinal cord ischemia.

PMID- 17533471
TI  - The S447X polymorphism of lipoprotein lipase: effect on the incidence of
      premature coronary disease and on plasma lipids.
AB  - OBJECTIVE: The objective of this study was to evaluate the effect of polymorphism
      S447X on plasma lipids of patients with premature coronary artery disease (CAD).
      METHODS: Plasma lipids and genotypes were determined in 2 groups: 313 patients
      with premature CAD (<55 years of age) and 150 controls without CAD. RESULTS:
      Frequency of the S447X polymorphism was 18% in patients with CAD and 23% in the
      control group. The S447X polymorphism of lipoprotein lipase is related to a
      decrease in plasma triglyceride concentrations in male patients with CAD, but
      this correlation is not observed in female patients. CONCLUSION: The presence of
      the S447X lipoprotein lipase polymorphism was not associated with the incidence
      of CAD.

PMID- 17533472
TI  - Association between risk factors for coronary artery disease and coronary disease
      in patients undergoing myocardial perfusion scintigraphy.
AB  - OBJECTIVES: To establish the degree of association between cardiovascular risk
      factors and the presence of coronary artery disease (CAD) in a group of patients
      undergoing myocardial perfusion scintigraphy (MPS). METHODS: The study included
      7183 patients who had undergone MPS. Using logistic regression analysis the odds
      ratios for the following risk factors were evaluated: age, gender, family
      history, body mass index, smoking, dyslipidemia, diabetes mellitus (DM) and
      systemic hypertension. Indicators for the presence of CAD were defined as:
      myocardial infarction, revascularization, angioplasty or an altered MPS. Analysis
      was based on the whole the group as well as on male and female subgroups. The
      impact of the risk factors in relation to age was also analyzed. RESULTS: A
      statistically significant association was observed between patient age and gender
      and the presence of CAD. For females, it was demonstrated that DM is the main
      modifiable risk factor for CAD. For males various modifiable risk factors were
      associated with the presence of CAD, particularly DM and dyslipidemia. In the
      analysis by age groups some risk factors showed a more expressive association.
      CONCLUSION: The main risk factors for CAD were aging and male gender. In relation
      to modifiable risk factors and the presence of CAD, the greatest associations for
      males were DM and dyslipidemia and for females DM. The most relevant factors for
      specific age groups were smoking for young men and DM and smoking for women
      between the ages of 40 and 50.

PMID- 17533473
TI  - Maximum heart rate in Brazilian elderly women: comparing measured and predicted
      values.
AB  - OBJECTIVE: This study sought to compare maximum heart rate (HRmax) values
      measured during a graded exercise test (GXT) with those calculated from
      prediction equations in Brazilian elderly women. METHODS: A treadmill maximal
      graded exercise test in accordance with the modified Bruce protocol was used to
      obtain reference values for maximum heart rate (HRmax) in 93 elderly women (mean
      age 67.1 +/- 5.16). Measured values were compared with those estimated from the
      "220-age" and Tanaka et al formulas using repeated-measures ANOVA. Correlation
      and agreement between measured and estimated values were tested. Also evaluated
      was the correlation between measured HRmax and volunteers age. RESULTS: Results
      were as follows: 1) mean HRmax reached during GXT was 145.5 +/- 12,5 beats per
      minute (bpm); 2) both the "220-age" and Tanaka et al (2001) equations
      significantly overestimated (p < 0.001) HRmax by a mean difference of 7.4 and
      15.5 bpm, respectively; 3) age was significantly (p < 0,001) and inversely
      related to measured HRmax. CONCLUSION: Based on these results, it can be
      concluded that both prediction equations significantly overestimated HRmax
      measured during maximal GXT in Brazilian elderly women, a finding that may have
      important implications when prescribing exercise intensity for this population.
      In addition, HRmax was inversely related to the volunteers age, suggesting that
      the chronotropic reserve continues to decline after age 60.

PMID- 17533474
TI  - Clinical and economic outcome of a cardiopulmonary and metabolic rehabilitation
      program.
AB  - OBJECTIVE: To evaluate the clinical and economic outcome of a Cardiopulmonary and
      Metabolic Rehabilitation Program (CPMR) created by an HMO. METHODS: The sample
      was comprised of 96 clients, divided into two groups of 48 individuals (treatment
      group--TG, individuals who participated in the CPMR program, and control group-
      CG, individuals who did not participate in the program) of both genders, with age
      ranging between 54 and 79 years. Training time of the TG was 22 (+/-3) months. To
      assess the clinical outcome before and after CPMR, exercise tolerance, plasma
      lipoprotein profile (TC, LDL-C, HDL-C, TC/HDL-C and triglycerides), resting blood
      pressure (BP), and body composition (Body mass index--BMI and Waist-to-hip ratio-
      W/HR) were determined. RESULTS: The TG presented the following results in the pre
      and post CPMR assessment, respectively: TC (mg/dL) 242.5 (+/-48,32) and 189.47(+/
      39.83); LDL-C (mg/dL) 162(+/-37.72) and 116.3(+/-33.28); HDL-C (mg/dL) 46.5(+/
      8.59) and 57.8(+/-10.36); Tg (mg/dL) 165.15(+/-90.24) and 113.29(+/-54.92);
      TC/HDL-C 5.42 (+/-1.10) and 3.35 (+/-0.81); VO2 peak (mL/Kg/min) 26.92 +/- 7 and
      32.64 +/- 5.92; BMI 29.35 (+/-3.93) and 28.12 (+/-3.55) for women and 29.17 (+/
      5.14) and 27.88 (+/-4.83) for men; W/HR 0.93(+/-0.05) and 0.94(+/-0.04) for women
      and 0.93(+/-0.07) and 0.92(+/-0.06) for men; BP (mmHg) 151(+/-13.89) and 132(+/
      9.56); DBP (mmHg) 83(+/-8.07) and 77(+/-5.92); monthly expenses CG (R$) 8,840.05
      (+/-5,656.58) and 8,978.32 (+/-5,500.78); monthly expenses TG (R$) 2,016.98 (+/
      2,861.69) and 1,470.73 (+/-1,333.25). CONCLUSION: In the group undergoing the
      CPMR Program, favorable clinical changes were observed in relation to the plasma
      lipoprotein profile, blood pressure, and exercise tolerance, with no relation to
      changes in medications.

PMID- 17533475
TI  - Arterial blood pressure in adolescents during exercise stress testing.
AB  - OBJECTIVE: Describe arterial blood pressure response in adolescents undergoing
      exercise stress testing. METHODS: This was a cross-sectional study conducted with
      218 adolescents (131 of whom were males), aged between 10 to 19 years, undergoing
      exercise stress testing. Maximum heart rate, total exercise time, maximum oxygen
      uptake, systolic blood pressure (SBP) and diastolic (DBP) at rest, during maximal
      physical exertion and at six minutes of recovery were measured. RESULTS: At rest,
      SBP values were greater in males and no difference was found in DBP between
      genders, although both increased with age. During exercise, SBP rose and DBP fell
      in both genders. SBP variation was greater in men, particularly in those over 14
      years of age. CONCLUSION: Analysis of results showed that during physical
      exercise, SBP had a direct relationship with the individuals age, weight, height
      and body mass index, whereas DBP bore a relationship to age only.

PMID- 17533476
TI  - Hypertension prevalence in the city of Formiga, MG, Brazil.
AB  - OBJECTIVES: To estimate hypertension prevalence and identify associated
      socioeconomic, demographic, and anthropometric variables. METHODS: A cross
      sectional study with probability sampling. TARGET POPULATION: people > or = 18
      years of age living in the urban area of Formiga, Minas Gerais state, and
      registered with the Family Health Program (Programa Saude da Familia-PSF), which
      covers 94% of the population. Two hundred and eighty-five subjects (131 men and
      154 women) were enrolled in the study. Criteria for the diagnosis of hypertension
      were the following: systolic blood pressure > or = 140 mmHg and/or diastolic
      blood pressure > or = 90 mmHg, or current use of antihypertensive medication. A
      standard questionnaire was used to collect socioeconomic and demographic data, as
      well as information on alcohol consumption, smoking, and physical activity level.
      RESULTS: Overall prevalence of hypertension in the target population was
      estimated at 32.7% (95% CI): 28.2-37.2), 31.7% in men and 33.6% in women. Among
      subjects with prescribed antihypertensive drugs, 66% reported taking their
      medication regularly. Hypertension prevalence increased steadily with increasing
      age (OR = 1.07; 95% CI: 1.05-1.10) and was positively associated with waist
      circumference (OR = 3.05; 95% CI: 1.49-6.22) and negatively associated with the
      level of physical activity (OR = 0.45; 95% CI: 0.25-0.82). CONCLUSION:
      Hypertension prevalence was very high in the adult population registered with the
      PSF in Formiga, representing a major public health problem. Intervention programs
      that boost physical activity, promote compliance with drug treatment, and focus
      on hypertensive subjects unaware of their condition are needed.

PMID- 17533477
TI  - Effects of bisoprolol on cardiac function and exercise in patients with heart
      failure.
AB  - OBJECTIVE: To assess the effects of bisoprolol on exercise capacity and
      ventricular function in patients with heart failure. METHODS: Clinical and
      hemodynamic variables, ventricular function and remodeling, and ergospirometry of
      patients with heart failure of different etiologies were evaluated before and
      after the administration of bisoprolol. RESULTS: Twenty-two patients were
      analyzed; one patient did not tolerate medication and 14 patients reached the
      study goal. The group consisted of 9 men and 5 women, the mean age was 52 (36-64)
      years, and patients were followed during 551 days (238-1109). We observed an
      improvement in NYHA functional class, reduction in resting heart rate (78.8+/-8.7
      vs 63+/-6.4 bpm, p <0.001), increase in left ventricular ejection fraction
      (31.3+/-8.5% vs 39+/-14.7%. p=0.043), and a tendency towards improved quality of
      life scores (31+/-20.6 vs 17.8+/-14.8. p=0.058). The maximum heart rate dropped
      during exercise (138.1+/-20.2 vs 116.7+/-27.1. p=0.01), as did peak oxygen
      consumption (20.9+/-6.8 vs 15.1+/-3.5. p<0.001); no change was observed on the
      EV/VCO2 slope. The effects were observed for all etiologies, including Chagas
      disease. CONCLUSION: Bisoprolol was safe and well tolerated in patients with
      heart failure. Bisoprolol therapy improved the symptoms, hemodynamic variables,
      as well as the cardiac function for all etiologies; however, it did not result in
      improved exercise capacity.

PMID- 17533478
TI  - Influences of rich in saturated and unsaturated fatty acids diets in rat
      myocardium.
AB  - OBJECTIVES: To study the influence of saturated (SFA) and unsaturated fatty acid
      (UFA) rich diets on mechanical function, morphology and oxidative stress in rat
      myocardium. METHODS: Male, 60-day-old Wistar rats were fed a control (n=8), a SFA
      (n=8), or a UFA-rich diet (n=8) for sixty days. Mechanical function was studied
      in isolated left ventricle papillary muscle under isometric and isotonic
      contractions, in basal conditions (1.25 mM calcium chloride) and after 5.2 mM
      calcium chloride and beta-adrenergic stimuli with 1.0 microM isoproterenol. Left
      ventricle fragments were used to study oxidative stress and morphology under
      light and electron microscopy. RESULTS: SFA and UFA-rich diets did not change
      myocardium mechanical function. Both diets caused oxidative stress, with high
      lipid hydroperoxide and low superoxide-dismutase concentrations. UFA rich diet
      decreased catalase expression and SFA rich diet decreased the amount of
      myocardial glutathione-peroxidase. Both diets promoted light ultrastructural
      injuries such as lipid deposits and cell membrane injuries. CONCLUSION: Results
      suggest that SFA and UFA rich diets do not alter isolated muscle mechanical
      function, but promote light myocardial morphological injuries and oxidative
      stress.

PMID- 17533479
TI  - Hypoplastic left heart syndrome: the influence of surgical strategy on outcomes.
AB  - OBJECTIVES: To report a surgical strategy for the Norwood procedure in the
      hypoplastic left heart syndrome (HLHS) that enables short hypothermic circulatory
      arrest time and aortic arch reconstruction with autologous pericardium patch, and
      to compare the results of the modified Blalock-Taussig (mBT) shunt with the right
      ventricle-to-pulmonary artery (RV-PA) conduit procedures as the source of
      pulmonary blood flow. METHODS: Retrospective study of 71 newborns with HLHS
      consecutively operated between March, 1999 and February, 2006. One technique for
      reconstruction of the neoaorta and two different techniques for reestablishment
      of the pulmonary blood flow were used: the mBT shunt in the first 37 newborns and
      RV-PA conduit in the last 34. Cannulation of the ductus arteriosus for arterial
      perfusion was the main part of the surgical strategy to reduce the hypothermic
      circulatory arrest time. RESULTS: In-hospital survival for the entire cohort was
      74.64%, or 67.57% and 82.35% for the mBT shunt and RV-PA conduit groups,
      respectively (p=0.1808). Mortality rates between the first and second palliation
      stages were 40% and 4.4% for the mBT shunt and RV-PA conduit groups, respectively
      (p=0.0054). Hypothermic circulatory arrest times were 45.79+/-1.99 min and
      36.62+/-1.62 min (p=0.0012), respectively. Late coarctation of the aorta occurred
      in five patients (7.2%). CONCLUSION: This surgical strategy resulted in short
      circulatory arrest time, low mortality and favorable morphology of the neoaorta,
      with low incidence of late coarctation of the aorta. The higher rate of survival
      to first palliation stage with the RV-PA conduit was not significant, but
      interstage mortality was statistically lower when compared with the modified
      Blalock-Taussig shunt procedure.

PMID- 17533480
TI  - [Case 2/2007: heart failure in a 49 year-old male with myocardial infarction].

PMID- 17533482
TI  - Research and teaching: essential components of a university hospital.

PMID- 17533481
TI  - Pressure response in Chagasic cardiomyopathy patients after using Sildenafil.
AB  - OBJECTIVE: To accurately verify the effect of Sildenafil on blood pressure (BP)
      and heart rate (HR) in individuals with Chagasic myocardiopathy (CMC) and severe
      systolic ventricular dysfunction (EF<40%) submitted to physical activity.
      METHODS: Twelve men with ejection fractions <40% and CMC confirmed by a
      serological test were assessed. The six-minute walk test (6MWT) was performed
      before and after administration of 50 mg of Sildenafil, with a 30 minute
      interval. Heart rate (HR), systolic blood pressure (SBP) and diastolic blood
      pressure were taken and compared before and after each 6MWT. For statistical
      analysis purposes, the study was divided into four stages: before the 6MWT and
      administration of Sildenafil (S1); after the 6MWT but before the administration
      of Sildenafil (S2); after the administration of Sildenafil but before the 6MWT
      (S3); and after the administration of Sildenafil and the 6MWT (S4). RESULTS:
      Participant ages ranged from 47 to 68 years (57.6 +/- 6.4). SBP and DBP after the
      6MWT and the administration of Sildenafil (S4) were lower than before taking the
      drug (S2): 134.2 +/- 15.1 versus 125.5 +/- 14.0 and 88.4 +/- 12.4 versus 83.0 +/-
      10.8, respectively. None of the patients reported any symptoms during the 6MWT.
      There were no differences in the distances walked during the 6MWT before or after
      taking Sildenafil (487.5+/-15.22 versus 505.3+/-18.45 meters, respectively)
      p=0.056, or in HR (before Sildenafil 75.5 +/- 8.79 and 96.8 +/- 10.36 bpm and
      after 77.1 +/- 9.81 and 96.1 +/- 12.97 bpm). CONCLUSION: A significant reduction
      in BP after physical activity while using Sildenafil was observed. However,
      during the six-minute walk test, the patients did not report any symptoms,
      indicating that this effect is not sufficient to cause clinical manifestations in
      CMC and heart failure patients.

PMID- 17533483
TI  - Point of view.

PMID- 17533484
TI  - Urticaria: current opinions about etiology, diagnosis and therapy.
AB  - In the last few decades an increasing understanding of the pathomechanisms
      involved in urticaria has highlighted the heterogeneity of different subtypes.
      According to the new European Academy of Allergology and Clinical
      Immunology/Global Allergy and Asthma European Network/European Dermatology Forum
      (EAACI/GA(2)LEN/ EDF) guidelines, urticaria subtypes can be grouped into
      spontaneous urticaria, which includes acute urticaria and chronic urticaria, the
      physical urticarias, and other urticaria disorders, including, for example,
      contact urticaria. Clarity of nomenclature is required not only to choose the
      correct measures in diagnosis and management, but also to compare data from
      different studies. Urticaria has a profound impact on quality of life and
      performance. Effective treatment is thus required in all cases where avoidance of
      eliciting factors is not feasible. For symptomatic relief, non-sedating H1
      antihistamines are the first choice in most subtypes of urticaria; however,
      double-blind controlled studies have shown that the dosages required may exceed
      those recommended for other diseases, e.g. allergic rhinitis. The current
      guidelines therefore suggest increasing the dosage up to four-fold, whereas
      alternative treatments should be reserved as add-on therapy for unresponsive
      patients.

PMID- 17533485
TI  - Intravenous immunoglobulin: properties, mode of action and practical use in
      dermatology.
AB  - Since they were first administered to patients with antibody deficiency disorders
      over 50 years ago, human intravenous immunoglobulin preparations have been used
      successfully to treat a rapidly increasing number of autoimmune and inflammatory
      disorders, among which are a series of cutaneous autoimmune and inflammatory
      diseases. These include dermatomyositis, Kawasaki's disease, a number of
      autoimmune bullous diseases, severe adverse drug reactions, and other autoimmune
      and/or allergic conditions, such as atopic dermatitis. Although only a minority
      of these indications (dermatomyositis, Kawasaki's disease) are officially
      registered or based on double-blind, placebo-controlled clinical studies, the
      observed efficacy and safety profile of currently available intravenous
      immunoglobulin sometimes makes this a treatment of choice for initiation of
      therapy or for replacement of more toxic alternatives, such as systemic
      immunosuppressive medications. The increasing use of intravenous immunoglobulin
      has been associated with further understanding of its mechanism(s) of action,
      clinical manipulation and associated side-effects, as well as the introduction of
      improved or new types of intravenous immunoglobulin. This paper reviews the
      current knowledge of the mode of action of intravenous immunoglobulin, its
      reported therapeutic effects in cutaneous disease, its mode of administration and
      safety profile, and compares the currently available intravenous immunoglobulin
      preparations.

PMID- 17533486
TI  - Human papilloma virus in skin, mouth and uterine cervix in female renal
      transplant recipients with or without a history of cutaneous squamous cell
      carcinoma.
AB  - Some human papillomaviruses are thought to be associated with skin cancer. In
      this pilot study, 21 female renal transplant carriers, 10 with a history of skin
      squamous cell carcinoma and 11 without, together with 9 age-matched healthy women
      were investigated for human papillomavirus DNA in sun-exposed (forehead) and less
      sun-exposed (buttock) skin, mouth and uterine cervix. Paraffin-embedded tumours
      from 9 of the patients with a history of squamous cell carcinoma were analysed.
      Healthy skin from both the healthy and the immunosuppressed individuals harboured
      a wide variety of papillomaviruses. In the healthy individuals, samples from less
      sun-exposed skin showed a lower prevalence of human papillomavirus DNA than
      corresponding samples from the immunosuppressed patients (4/9 and 7/9,
      respectively). Among the immunosuppressed patients, human papillomavirus DNA was
      found as frequently in buttock samples (17/21) as in forehead samples (17/20).
      There was no increased prevalence of human papillomavirus in the cervix or mouth
      samples from the immunosuppressed patients.

PMID- 17533487
TI  - Expression of allograft inflammatory factor-1 in inflammatory skin disorders.
AB  - Allograft inflammatory factor-1 (AIF-1) is an evolutionarily conserved,
      inflammatory protein produced by activated macrophages during chronic transplant
      rejection and in inflammatory brain lesions. Since T-cell-mediated inflammation
      is common to various dermatoses and nothing is known about AIF-1 in skin, we
      studied its protein expression at the tissue level and regulation in monocytic
      cell lines by various agents. Using immunohistochemistry, we found that AIF-1 is
      expressed at low levels in normal skin, but is highly upregulated in various
      inflammatory skin disorders, such as psoriasis, lichen planus, graft-versus-host
      disease and mycosis fungoides. The main cell types expressing AIF-1 in affected
      skin are macrophages and Langerhans' cells. We also show by real-time PCR that
      AIF-1 mRNA levels in monocytic THP-1 and U937 cell lines are significantly
      upregulated by retinoic acid as well as a number of cytokines. We conclude that
      AIF-1 may mediate survival and pro-inflammatory properties of macrophages in skin
      diseases.

PMID- 17533488
TI  - Serum antioxidant capacity in polymorphic light eruption.
AB  - Polymorphic light eruption is one of the few dermatological diseases in which
      some antioxidants have been said to be reduced in both the epidermis and the
      blood. This study measured the hydrosoluble antioxidant capacity in the serum of
      patients with polymorphic light eruption, using a commercially available kit. All
      patients were tested in winter, in order to avoid the influence of exposure to
      ultraviolet light. The results showed that a hydrosoluble antioxidant capacity
      was significantly decreased (by 29%) in patients with polymorphic light eruption,
      and b) that females (both patients and controls) has less hydrosoluble
      antioxidant capacity (by 27%) than males. In addition, the hydrosoluble
      antioxidant capacity values for females with polymorphic light eruption increased
      significantly with age, possibly accounting for the well-known propensity of
      young women to polymorphic light eruption. These last observations have not been
      reported previously.

PMID- 17533489
TI  - Spectrophotometric analysis of melanocytic naevi during pregnancy.
AB  - Malignant melanoma is the most common cancer during pregnancy, but it is unknown
      whether melanocytic naevi in general are activated. A total of 381 melanocytic
      naevi in 34 Caucasian primigravidae were examined using spectrophotometric
      intracutaneous analysis (SIAscopy) technology in early pregnancy and prior to
      delivery. The Siagraphs of each naevus were then compared in order to evaluate
      changes over time. A total of 163 melanocytic naevi in 21 nulliparous women
      served as an additional control group. At the first visit none of the Siagraphs
      examined for the case or control groups aroused suspicion of dysplastic naevus or
      melanoma and no significant structural changes were noted during the observation
      period. However, 2.1% of the melanocytic naevi in the pregnant group increased
      and 1.3% decreased in size. Corresponding figures in the non-pregnant group were
      1.8% and 0%, respectively. Only one naevus in a pregnant woman increased slightly
      in epidermal pigmentation, and a decrease in pigmentation was noted in 3.7% of
      the melanocytic naevi in the cases and 1.8% in the controls. None of the
      differences within or between the groups was statistically significant. We
      conclude that pregnancy does not influence the appearance of pigmented naevi. A
      changing naevus during pregnancy should be examined carefully and considered for
      excision and histopathology.

PMID- 17533490
TI  - Pigmented basal cell carcinoma--comparing the diagnostic methods of SIAscopy and
      dermoscopy.
AB  - Pigmented basal cell carcinomas can be difficult to distinguish clinically from
      melanoma. Dermoscopy has proven to be useful in the differential diagnosis of the
      two tumour types. SIAscopy (Spectrophotometric intracutaneous analysis) is a
      fairly new technique of imaging pigmented skin lesions that has been presented
      previously as a useful tool in diagnosing melanoma. The aim of this study was to
      evaluate whether SIAscopy can be useful in diagnosing pigmented basal cell
      carcinomas. Twenty-one pigmented basal cell carcinomas were analysed, comparing
      dermoscopic and SIAscopic findings. The results, in this limited setting, show
      that SIAscopy has no advantages over dermoscopy when diagnosing pigmented basal
      cell carcinomas. On the contrary, pigmented basal cell carcinomas show, in
      SIAscopy, similar features to those previously reported for melanoma.

PMID- 17533491
TI  - High prevalence of oncogenic human papilloma virus in women not attending
      organized cytological screening.
AB  - Since the introduction of organized cytological screening in Sweden, most women
      currently presenting with cervical cancer are those who have not attended the
      programme and who have no cytological screening history. The aims of this study
      were: (i) to measure the response rate among women not attending organized
      cytological screening who were offered a device for self-sampling a vaginal smear
      at home; (ii) to examine the prevalence of high-risk human papilloma virus (HPV)
      among women performing self-sampling. Women aged 35-50 years, who had not
      participated in organized cytological screening for more than 6 years, were
      offered the opportunity to collect vaginal samples at home using a self-sampling
      device (Qvintip). The material collected was analysed for high-risk HPV using the
      Hybrid Capture 2 method. Of 369 women included in the study, 179 (49%) ordered
      the self-sampling device and 117 (32%) performed self-sampling at home and sent
      the sample to our laboratory for analysis. The mean prevalence of high-risk HPV
      was 26% (30/117), 31% (25/80) in women aged 35-42 years and 14% (5/37) in women
      aged 43-50 years. There was no significant difference in the participation rate
      with regard to age. The prevalence of high-risk HPV in women not covered by
      organized screening was considerably higher than in the general population;
      therefore they may represent a category at high risk of cervical cancer. The
      study shows that the use of a disposable self-sampling device for HPV testing is
      a relevant method to increase the participation rate in countries with organized
      cytological screening.

PMID- 17533493
TI  - Health-related quality of life and nail disorders.
AB  - Health-related quality of life (HRQoL) measurements in clinical practice ensure
      that treatment and evaluations focus on the patient rather than the disease. To
      verify whether these measurements are also relevant in a minor dermatological
      disease and whether a generic routine assessment is sufficient to capture
      different aspects of quality of life, we studied patients affected by nail
      disorders. The Skindex-29, the 12-item General Health Questionnaire and the 36
      item Short Form of the Medical Outcomes Study questionnaires were used. A total
      of 114 patients were enrolled: 31% men aged 48 +/- 15 years and 69% women aged 49
      +/- 14 years (mean +/- SD). The mean values of SF-36 scales in nail disorders
      were higher than those reported for minor skin diseases, and Skindex-29 values
      were lower. A duration of disease > or =1 year was associated with higher Skindex
      29 scores on the symptom and emotions scales. Patients with onychomycosis have
      higher values on the Skindex-29 social functioning scale compared with other nail
      disorders. The use of HRQoL measurements in routine clinical activities allows us
      to depict how nail disorders affect patients and show how relevant some neglected
      aspects, such as pain or emotional trauma, are and offers us the opportunity to
      address these issues in a patient-centred approach to treatment.

PMID- 17533492
TI  - Clinical and microbiological comparisons of isotretinoin vs. tetracycline in acne
      vulgaris.
AB  - The aim of this study was to compare the clinical and microbiological effect on
      Propionibacterium acnes of oral tetracycline plus topical adapalene vs. oral
      isotretinoin in moderate to severe acne vulgaris. Male and female acne patients
      with moderate or severe inflammatory disease were enrolled and assigned randomly
      to 6 months of treatment with oral tetracycline hydrochloride plus topical
      adapalene, or oral isotretinoin, in a controlled, open study. After cessation of
      oral treatment the antibiotic-treated group received topical adapalene for the 2
      month follow-up period. Clinical and microbiological assessments were performed.
      Skin samples for microbial identification and quantification were taken at
      baseline, after 2, 4 and 6 months of treatment, and 2 months after cessation of
      treatment. Patients treated with isotretinoin showed prolonged significant
      remission compared with the other group. The density of resistant
      propionibacteria did not change significantly in any of the groups and there was
      no correlation between resistant P. acnes and the clinical response in any of the
      regions investigated. Antibiotic treatment was found to be a good alternative to
      isotretinoin, regardless of the presence of antibiotic-resistant P. acnes,
      although isotretinoin had a better effect, with prolonged remission after
      treatment.

PMID- 17533494
TI  - Sera from patients with palmoplantar pustulosis show immunoreactivity against
      endothelial cells.

PMID- 17533495
TI  - Chronic urticaria and mild arthritis associated with autoimmune thyroid disease:
      successful treatment with L-thyroxine.

PMID- 17533496
TI  - Infliximab: a novel treatment option for refractory orofacial granulomatosis.

PMID- 17533497
TI  - Safe usage of isotretinoin in a woman with latent acute intermittent porphyria.

PMID- 17533498
TI  - G-CSF-producing giant squamous cell carcinoma (SCC): changes in serum G-CSF in
      parallel with SCC antigen.

PMID- 17533499
TI  - Allergic contact dermatitis from luliconazole: implication of the dithioacetal
      structure.

PMID- 17533500
TI  - Late onset of cardiac tumour in naevoid Basal cell carcinoma (Gorlin) syndrome.

PMID- 17533501
TI  - Multifocal cutaneous leishmaniasis: a new clinical presentation of the disease.

PMID- 17533502
TI  - Generalized pruritus revealing hereditary haemochromatosis.

PMID- 17533503
TI  - Rowell syndrome with palmoplantar involvement and suspected epitope spreading.

PMID- 17533504
TI  - Striking effect of the IL-1 receptor antagonist anakinra in chronic urticarial
      rash with polyclonal increase in IgA and IgG.

PMID- 17533505
TI  - Polypoid basal cell carcinoma as a new variant of basal cell carcinoma: three
      Korean cases.

PMID- 17533506
TI  - Acquired primary syphilis on a child's lip.

PMID- 17533508
TI  - Prenatal immune responses to Plasmodium falciparum erythrocyte membrane protein 1
      DBL-alpha domain in Gabon.
AB  - In areas where malaria transmission is stable, infants are often born to mothers
      who had Plasmodium falciparum infections during pregnancy. A significant number
      become exposed to infected erythrocytes or soluble parasite products with
      subsequent fetal immune priming or tolerance in utero. We performed ELISA to
      asses IgG and IgM seropositivity rates against three PfEMP1 DBL-alpha domains
      from 42 maternal-cord paired samples obtained at delivery from a hyperendemic
      area in Gabon. IgG was present in up to 80% of the cord serum samples, while IgM
      was found in only 20% of the same samples. These levels were not dependent on the
      parity of the mother or the peripheral and placental infectious status. The
      presence of IgM against DBL-alpha domain in cord serum samples suggests that this
      component is able to cross the placental barrier and mount a fetal immune
      response.

PMID- 17533509
TI  - A twin study of auditory processing indicates that dichotic listening ability is
      a strongly heritable trait.
AB  - We administered tests commonly used in the diagnosis of auditory processing
      disorders (APDs) to twins recruited from the general population. We observed
      significant correlations in test scores between co-twins. Our analyses of test
      score correlations among 106 MZ and 33 DZ twin pairs indicate that dichotic
      listening ability is a highly heritable trait. Dichotic listening is the ability
      to identify and distinguish different stimuli presented simultaneously to each
      ear. Deficits in dichotic listening skills indicate a lesion or defect in
      interhemispheric information processing. Such defects or lesions can be prominent
      in elderly listeners, language-impaired children, stroke victims, and individuals
      with PAX6 mutations. Our data indicates that other auditory processing abilities
      are influenced by shared environment. These findings should help illuminate the
      etiology of APDs, and help to clarify the relationships between auditory
      processing abilities and learning/language disorders associated with APDs.

PMID- 17533510
TI  - Recurrent infrasellar clival craniopharyngioma.
AB  - The patient is a 44-year-old man who underwent resection of a posterior
      nasopharynx tumor 12 years earlier via left lateral rhinotomy approach. The final
      pathological analysis indicated the tumor was a craniopharyngioma, and the
      patient subsequently underwent focal radiation. The patient returned to medical
      attention complaining of dysequilibrium. A neurologic exam was nonfocal. Magnetic
      resonance imaging revealed a clival mass, separate from the sella turcica, with
      imaging characteristics concerning for chordoma or primary bone tumor (Fig. 1).
      The lesion was resected via an endoscope-assisted endonasal transsphenoidal
      approach, with gross total resection achieved. Intraoperatively, the mass was
      noted to erode through the posterior nasopharynx, without extension superiorly
      into the sella or posteriorly through the clival dura (i.e., lesion was
      infrasellar). The final pathological results indicated the tumor was
      adamantinomatous craniopharyngioma.

PMID- 17533511
TI  - Role of alpha adrenoceptors in the nucleus accumbens in the control of accumbal
      noradrenaline efflux: a microdialysis study with freely moving rats.
AB  - Microdialysis technique was used to study the effects of the locally applied
      alpha adrenoceptor agonist phenylephrine and antagonist phentolamine on the basal
      noradrenaline efflux as well as on the noradrenaline uptake inhibitor desipramine
      elicited noradrenaline efflux in the nucleus accumbens (NAc) of freely moving
      rats. Tetrodotoxin reduced basal noradrenaline efflux by 72%, whereas desipramine
      increased it by 204%. Phenylephrine reduced the basal noradrenaline efflux by 32%
      and phentolamine blocked this effect. Phentolamine elevated the basal
      noradrenaline efflux by 150% and phenylephrine counteracted this effect. The
      desipramine-elicited noradrenaline efflux was not affected by phenylephrine, but
      enhanced by phentolamine. Desipramine counteracted the effects of phenylephrine
      and potentiated those of phentolamine. These results indicate that the accumbal
      noradrenaline efflux is under inhibitory control of alpha adrenoceptors that are
      suggested to be presynaptically located on adrenergic nerve terminals in the NAc.
      Furthermore, this study suggests that the conformational state of alpha
      adrenoceptors varies across the available amount of noradrenaline. The clinical
      impact of these data is discussed.

PMID- 17533512
TI  - Arabidopsis EIN2 modulates stress response through abscisic acid response
      pathway.
AB  - The nuclear protein ETHYLENE INSENSITIVE2 (EIN2) is a central component of the
      ethylene signal transduction pathway in plants, and plays an important role in
      mediating cross-links between several hormone response pathways, including
      abscisic acid (ABA). ABA mediates stress responses in plants, but there is no
      report on the role of EIN2 on plant response to salt and osmotic stresses. Here,
      we show that EIN2 gene regulates plant response to osmotic and salt stress
      through an ABA-dependent pathway in Arabidopsis. The expression of the EIN2 gene
      is down-regulated by salt and osmotic stress. An Arabidopsis EIN2 null mutant was
      supersensitive to both salt and osmotic stress conditions. Disruption of EIN2
      specifically altered the expression pattern of stress marker gene RD29B in
      response to the stresses, but not the stress- or ABA-responsive genes RD29A and
      RD22, suggesting EIN2 modulates plant stress responses through the RD29B branch
      of the ABA response. Furthermore, disruption of EIN2 caused substantial increase
      in ABA. Lastly, our data showed that mutations of other key genes in ethylene
      pathway also had altered sensitivity to abiotic stresses, indicating that the
      intact ethylene may involve in the stress response. Taken together, the results
      identified EIN2 as a cross-link node in ethylene, ABA and stress signaling
      pathways, and EIN2 is necessary to induce developmental arrest during seed
      germination, and seedling establishment, as well as subsequent vegetative growth,
      thereby allowing the survival and growth of plants under the adverse
      environmental conditions.

PMID- 17533513
TI  - The moss genes PpSKI1 and PpSKI2 encode nuclear SnRK1 interacting proteins with
      homologues in vascular plants.
AB  - The yeast Snf1, animal AMPK, and plant SnRK1 protein kinases constitute a family
      of related proteins that have been proposed to serve as metabolic sensors of the
      eukaryotic cell. We have previously reported the characterization of two
      redundant SnRK1 encoding genes (PpSNF1a and PpSNF1b) in the moss Physcomitrella
      patens. Phenotypic analysis of the snf1a snf1b double knockout mutant suggested
      that SnRK1 is important for the plant's ability to recognize and adapt to
      conditions of limited energy supply, and also suggested a possible role of SnRK1
      in the control of plant development. We have now used a yeast two-hybrid system
      to screen for PpSnf1a interacting proteins. Two new moss genes were found, PpSKI1
      and PpSKI2, which encode highly similar proteins with homologues in vascular
      plants. Fusions of the two encoded proteins to the green fluorescent protein
      localize to the nucleus. Knockout mutants for either gene have an excess of
      gametophores under low light conditions, and exhibit reduced gametophore stem
      lengths. Possible functions of the new proteins and their connection to the SnRK1
      kinase are discussed.

PMID- 17533515
TI  - Embryotoxic effects of nonylphenol and octylphenol in sea urchin Arbacia lixula.
AB  - Nonylphenol (NP) and octylphenol (OP), both of which are biodegradation products
      of alkylphenols, are widely used in industrial applications and in some domestic
      products. These chemicals are found widely in surface water and aquatic
      sediments. We have carried out a comparative embryotoxicity analysis of the
      effects of increasing concentrations of NP (seven concentrations ranging from
      0.937 to 18.74 microg/l) and OP (six concentrations ranging from 5 to 160
      microg/l) on embryos of the sea urchin Arbacia lixula. The indicators evaluated
      were larval malformations, developmental arrest and embryonic/larval mortality.
      The results revealed that low concentrations of these chemicals (NP, OP)
      generally caused malformations in the skeletal system. High concentrations (18.74
      microg NP/l, 160 microg OP/l) were found to inhibit the growth of embryos in the
      early life stages by preventing mitosis. We conclude that NP and OP present a
      major risk to the normal development of A. lixula at the low concentrations that
      have been recorded in the environment. These chemicals are therefore most likely
      to represent an ecological hazard at the population level given the cumulative
      effects of other environmental pollutants.

PMID- 17533514
TI  - The effect of substitution of the N-acetyl groups of N-acetylgalactosamine
      residues in chondroitin sulfate on its degradation by chondroitinase ABC.
AB  - Chondroitinase ABC is a lyase that degrades chondroitin sulfate, dermatan sulfate
      and hyaluronic acid into disaccharides. The purpose of this study was to
      determine the ability of chondroitinase ABC to degrade chondroitin sulfate in
      which the N-acetyl groups are substituted with different acyl groups. The bovine
      tracheal chondroitin sulfate A (bCSA) was N-deacetylated by hydrazinolysis, and
      the free amino groups derivatized into N-formyl, N-propionyl, N-butyryl, N
      hexanoyl or N-benzoyl amides. Treatment of the N-acyl or N-benzoyl derivatives of
      bCSA with chondroitinase ABC and analysis of the products showed that the N
      formyl, N-hexanoyl and N-benzoyl derivatives are completely resistant to the
      enzyme. In contrast, the N-propionyl or N-butyryl derivatives were degraded into
      disaccharides with slower kinetics compared to that of unmodified bCSA. The rate
      of degradation of bCSA derivatives by the enzyme was found to be in the order of
      N-acetyl>N-propionyl>>N-butyryl bCSA. These results have important implications
      for understanding the interaction of N-acetyl groups of glycosaminoglycans with
      chondroitinase ABC.

PMID- 17533516
TI  - Postprocedural resistance of the target lesion is a strong predictor of
      subsequent revascularization: assessment by a novel lesion-specific physiological
      parameter, the epicardial resistance index.
AB  - Objective evaluation of the functional significance of individual stenosis in
      patients with multiple lesions is crucial when performing percutaneous coronary
      intervention (PCI). Here we propose a novel lesion-specific parameter, the
      epicardial resistance index (ERI), which is derived from intracoronary pressure
      measurements, and validate its clinical usefulness. The ERI is defined as the
      ratio of the resistance of an epicardial coronary stenosis to that of downstream
      myocardium. After obtaining intracoronary pressure data by pull-back of a 0.014''
      pressure wire, the ERI was calculated as the trans-lesional pressure gradient
      divided by (Pd-Pv) at maximum hyperemia, where Pd = the mean distal coronary
      pressure in the absence of any stenosis and Pv = the central venous pressure.
      Using 170 measurements obtained from 75 patients, the correlation of ERI with
      parameters obtained from quantitative coronary angiography (QCA) and
      intravascular ultrasound (IVUS) was studied. ERI showed a significant correlation
      with the QCA-derived percent diameter stenosis (r = 0.67, P < 0.001), and with
      the IVUS-derived minimum luminal area (r = 0.68, P < 0.001). In 55 patients who
      underwent PCI with bare metal stents, a postprocedural target lesion ERI value
      greater than 0.16 strongly predicted the need for subsequent revascularization
      within six months (81% sensitivity and 80% specificity). The ERI is a useful
      pressure-derived hemodynamic parameter that correlates with anatomical
      parameters. In addition, the postprocedural resistance of the target lesion
      indicated by the ERI is a reliable predictor of the late outcome of PCI.

PMID- 17533517
TI  - Efficacy and safety of low-dose pioglitazone after primary coronary angioplasty
      with the use of bare metal stent in patients with acute myocardial infarction and
      with type 2 diabetes mellitus or impaired glucose tolerance.
AB  - Thiazolidinediones (TZDs) have beneficial effects on markers of cardiovascular
      risk in patients with type 2 diabetes mellitus (DM). This study aimed to
      investigate the efficacy and safety of low-dose pioglitazone (15 mg per day) in
      patients with acute myocardial infarction (AMI) and type 2 DM or impaired glucose
      tolerance (IGT) treated with coronary angioplasty using bare metal stent (BMS).
      In 56 patients, pioglitazone was orally administered for 6 months after stenting
      (pioglitazone group). The incidence of in-stent restenosis (ISR) and left
      ventricular end-diastolic volume index (LVEDVI) at acute phase and 6 months after
      stenting in these patients were retrospectively compared with those in the other
      37 patients (control group) treated without pioglitazone. No adverse events
      including death, emergency bypass surgery, and reinfarction, occurred in any
      patients in the hospital. There was no congestive heart failure (CHF) during a
      follow-up period in the pioglitazone group. At 6 months after stenting, the
      overall angiographic ISR rate was significantly lower in the pioglitazone group
      than in the control group (28.6% vs 48.6%, P = 0.049). In patients with
      hemoglobin A1c (HbA1c) <7.0% at follow-up, the ISR rate was also significantly
      lower in the pioglitazone group than in controls (21.3% vs 44.8%, P = 0.03).
      Delta-LVEDVI (defined as follow-up LVEDVI minus acute LVEDVI) was similar between
      the pioglitazone group and control group (0.13 vs 5.16 ml/m(2), P = 0.482). Low
      dose pioglitazone seems to have a potential to reduce ISR and does not adversely
      affect LV remodeling after AMI treated with coronary angioplasty using BMS in
      patients with type 2 DM or IGT.

PMID- 17533518
TI  - Impact of post-dilatation with a focal expanding balloon for optimization of
      intracoronary stenting.
AB  - Optimal stenting frequently requires additional stent post-dilatation following
      initial stent deployment. Stent post-dilatation using a focal expanding balloon
      (FB) that grows 0.5 mm larger centrally may achieve a larger final stent lumen
      with fewer stent edge injuries as compared to use of a conventional unidiameter
      balloon (UB). In the present prospective study, of 128 stented lesions in 122
      patients, 63 lesions had stents dilated with FB (Group F), while 65 lesions had
      stents dilated with UB (Group U). All balloons for stent post-dilatation were
      half-sized up to reference diameter by on-line quantitative coronary analysis.
      There were no differences in the reference diameter, pre-procedural minimal lumen
      diameter (MLD), balloon/artery ratio, and final balloon pressure between the two
      groups. Post-procedural MLD in Group F was significantly larger than that in
      Group U (3.03 +/- 0.43 vs 2.80 +/- 0.47 mm, P < 0.001). Stent edge injury
      occurred in 4 patients, and stent thrombosis in 2 patients in Group U, but not in
      Group F. Minimal lumen diameter at 6 months in Group F was significantly larger
      than that in Group U (2.05 +/- 0.63 vs 1.82 +/- 0.66 mm, P < 0.05), and incidence
      of restenosis was significantly lower in Group F than Group U (9% vs 22%, P <
      0.05). By using a focal expanding balloon for stent optimization, a larger stent
      lumen can be obtained safely, and subsequent incidence of restenosis can be
      reduced.

PMID- 17533519
TI  - The role of paraoxonase (PON) enzyme in the extent and severity of the coronary
      artery disease in type-2 diabetic patients.
AB  - Increased coronary artery disease (CAD) risk is well established in diabetes
      mellitus (DM). Paraoxonase (PON) enzyme is known to have protective effects on
      lipid peroxidation. This study aimed to investigate the changes in PON activity
      levels with duration of DM as well as the role of PON activity in progression of
      CAD. Eighty-four consecutive diabetic patients (mean age 58 years, 46 men) who
      underwent coronary angiography for diagnostic purposes were examined. Before the
      angiography, fasting venous blood samples were taken for PON enzyme activity,
      thiobarbituric acid reactive substances (TBARS), and routine biochemical
      parameters. Severity and extent of coronary atherosclerosis were scored
      numerically using the Gensini scoring system. The population was divided into
      three groups according to Gensini score: Group 1, mild CAD; Group 2, moderate
      CAD; Group 3, severe CAD. Group 1 had higher PON levels and shorter DM duration
      than those of Group 3. Gensini score was significantly correlated with, PON
      activity (r = -0.361) and apo-AI (r = -0.375). TBARS (r = -0.290) and the
      duration of DM (r = -0.336) also showed a significant correlation with PON
      activity levels. Also, multivariate linear regression and Pearson correlation
      analyses showed that PON activity (P = 0.04), apo-AI levels (P = 0.01), and the
      duration of DM (P = 0.003) were significantly associated with Gensini score.
      Paraoxonase activity decreases parallel to DM duration. The lack of protective
      effect of PON enzyme on lipid peroxidation may be a factor in acceleration of CAD
      in DM.

PMID- 17533520
TI  - Insulin resistance and acute coronary syndrome in the young Japanese population
      have a strong association.
AB  - There are few data regarding acute coronary syndrome (ACS) in young Japanese
      patients. We examined the risk factors for ACS in young Japanese patients,
      especially impaired glucose metabolism. From a database of 789 consecutive
      patients admitted to our hospital with ACS between 2000 and 2005, we compared
      risk factors of patients divided into two age categories: < or =45 years (group
      Y, n = 41) and > or =46 years (group O, n = 748). All patients in group Y were
      male. Overt diabetes, hypertension, and a family history of ischemic heart
      disease were not so important to group Y. Higher triglyceride (160.5 +/- 86.0 vs
      133.9 +/- 75.2 mg/dl, P = 0.0296) and lower high-density lipoprotein cholesterol
      (43.9 +/- 12.1 vs 48.7 +/- 13.5 mg/dl, P = 0.027) concentrations were present in
      group Y. We obtained data concerning insulin resistance in 326 of 789 patients.
      Although the incidence of impaired glucose tolerance was similar between the
      groups (31% vs 31%, not significant), a higher homeostasis model assessment
      insulin resistance index (2.26 +/- 2.03), indicating insulin resistance, was
      present in group Y. Insulin resistance might be correlated with the development
      of ACS in the young adult Japanese population.

PMID- 17533521
TI  - Altered left ventricular-arterial coupling precedes pump dysfunction in early
      heart failure.
AB  - The objective of this study was to define alterations in ventricular-arterial (V
      A) coupling early in the development of tachycardia-induced heart failure (HF).
      Although HF is characterized by impaired V-A coupling, the temporal relationship
      of these derangements to overt left ventricular (LV) dysfunction is unknown. Six
      anesthetized dogs instrumented with LV manometers and piezoelectric crystals were
      studied before and after 24 h of rapid ventricular pacing (RVP). V-A coupling was
      indexed by the ratio between the end-systolic pressure-volume relation slope
      (endsystolic elastance, E(ES)) and effective arterial elastance (E(A)), and
      mechanical efficiency by the ratio of stroke work (SW) to pressure-volume area
      (PVA). After RVP, there was no significant depression of LV function, but E(A)
      and total peripheral resistance (R(T)) were increased (P < 0.05), indicating
      increased arterial load. After RVP, E(ES)/E(A) and SW/PVA were maintained during
      unstressed conditions, but upon changes in load induced by phenylephrine,
      E(ES)/E(A) declined more precipitously with equivalent increases in R (T) (slope
      E(ES)/E(A)-R(T) relation -16.7 +/- 4.6 vs -5.8 +/- 4.0 ml/mmHg.min, P < 0.025).
      Furthermore, after RVP there was significant (P < 0.05) blunting of dobutamine
      induced augmentation of E(ES), E(ES)/E(A), and SW/PVA. Thus, after RVP there was
      a distinct loss of V-A coupling reserve during afterload and catecholamine
      stress. V-A coupling defects occur early in the development of tachycardia
      induced HF prior to significant pump dysfunction, and are manifested primarily
      during hemodynamic and inotropic stress.

PMID- 17533522
TI  - Expression of interferon-gamma and interleukin-4 production in CD4+ T cells in
      patients with chronic heart failure.
AB  - The prevalence of inflammation is high among patients with chronic heart failure
      (CHF). Reduced ejection fraction was associated with frequency of CD4(+) T cells
      of leukocytes. Therefore, we investigated inflammatory cytokines of expression
      markers in CD4(+) T cells in patients with CHF. Blood samples were obtained from
      103 patients with CHF, from 83 patients with stable angina (SA), and from 57
      controls. Interferon-gamma (IFN-gamma)-positive CD4(+) T cells and interleukin-4
      (IL-4)-positive CD4(+) T cells were analyzed using 3-color flow cytometry. The
      frequency (%) of IFN-gamma-positive CD4(+) T cells increased in patients with CHF
      compared with those with SA and controls (CHF: 28.3 +/- 13.8, SA: 23.50 +/-
      10.38, controls: 19.00 +/- 7.45, P < 0.001). There was no significant difference
      in the frequency of IL-4-positive CD4(+) T cells among the three groups. The
      frequencies of CD4(+) T cells that stained for IFN-gamma decreased from 32.37% +/
      16.40% on admission to 26.91% +/- 12.53% after 2 weeks in 26 patients with CHF.
      B-type natriuretic peptide (pg/ml) and high-sensitivity C-reactive protein
      (mg/dl) levels decreased from 251.7 +/- 150.4 and 0.64 +/- 0.78 on admission to
      208.2 +/- 166.4 and 0.36 +/- 0.34 after 2 weeks in the 26 patients with CHF. We
      have demonstrated expression of IFN-gamma production of CD4(+) T cells during
      CHF. Prevention of unwanted T cell activation could represent a new target in the
      treatment of CHF.

PMID- 17533524
TI  - Percutaneous stenting of bilateral central venous occlusions in a hemodialysis
      patient.
AB  - Upper-extremity central venous obstruction is often first recognized when an
      arteriovenous fistula is made for hemodialysis at an ipsilateral site. We
      encountered a case of markedly expanded edema after making an arteriovenous
      fistula in the left forearm. Systemic venography showed that the bilateral
      brachiocephalic veins and right subclavian vein were occluded. Implantation of a
      self-expandable stent in the left brachiocephalic vein relieved the edema.
      However, recurrence of similar edema and occlusion of the left brachiocephalic
      vein were noted after 1.5 years. The left brachiocephalic vein was then
      recanalized by ballooning and additional stent implantation, and a stent was
      implanted between the superior vena cava and right subclavian vein. Simultaneous
      reconstruction of the bilateral central venous obstruction by percutaneous
      intervention rather than surgical repair was suitable for this patient because of
      previous thoracoplasty. We also believe that this method can provide an
      opportunity to select the suitable forearm for making an arteriovenous fistula,
      in which the ipsilateral central vein will exhibit little restenosis.

PMID- 17533523
TI  - Outcome of cardioverter-defibrillator implant in patients with arrhythmogenic
      right ventricular cardiomyopathy.
AB  - The aim of the present study was to investigate outcomes of implantable
      cardioverter-defibrillator (ICD) treatment in patients with arrhythmogenic right
      ventricular cardiomyopathy (ARVC). We reviewed baseline/follow-up data of 15
      consecutive ARVC patients (mean age 55 +/- 15 years) and 30 randomly drawn
      patients with coronary artery disease (CAD) (mean age 60 +/- 10 years) with
      matching durations of follow-up (all implanted with ICDs for primary/secondary
      prevention of sudden death). At implant, appropriate placement of the RV lead was
      more difficult in ARVC patients. During follow-up (median 41 months), appropriate
      interventions for any ventricular tachyarrhythmias occurred in 8 (53%) ARVC
      patients and 17 (57%) CAD patients, but the occurrence of high rate (>240
      beats/min) ventricular tachyarrhythmias was higher in ARVC patients.
      Inappropriate ICD interventions occurred in 5 (33%) ARVC patients and 10 (33%)
      CAD patients. Lead-related adverse events requiring surgical revision occurred in
      7 (47%) ARVC patients as compared with 4 (13%) CAD patients (P = 0.0004). While
      ICD implantation is highly effective for prevention of sudden death in ARVC, it
      does carry elevated burdens of long-term lead-related adverse events. These
      findings underline the need of careful follow-up in ARVC aimed at early
      recognition of complications that can impair ICD function.

PMID- 17533525
TI  - Double-filter technique for deployment of a permanent inferior vena cava filter
      while avoiding the risk of pulmonary embolism from a thrombus trapped by a
      temporary filter.
AB  - Because temporary caval filters have not been associated with any long-term
      complications, their use seems practical as long as indications are accurately
      assessed. However, problems about further dealing with the emboli trapped in a
      temporary filter remain. This case report describes a new approach to managing a
      thrombus captured by a temporary filter during the exchange for a permanent
      filter. We applied the Antheor temporary filter (Boston Scientific, Natick, MA,
      USA) as the device for thrombus capturing, then successfully placed the permanent
      filter with no clinical evidence of pulmonary embolism. Intravascular ultrasound
      was also useful for monitoring the entire procedure.

PMID- 17533526
TI  - Resolution of acromegalic cardiomyopathy in mild acromegalic physical abnormality
      after short-term octreotide therapy.
AB  - Congestive heart failure developed in a 42-year-old man who had very mild
      acromegalic features. Echocardiography showed a marked dilatation of the left
      ventricle and decreased systolic function. Laboratory examinations revealed the
      elevated levels of growth hormone and insulin-like growth factor-1 and pituitary
      microadenoma was demonstrated by magnetic resonance imaging. Although the
      extensive conventional medical treatment was ineffective, short-term addition of
      somatostatin analog, octreotide, rapidly improved his cardiac function. After
      discontinuation of octreotide, further improvement was observed with minimal
      residual diastolic dysfunction. All medical treatment could be stopped after
      successful trans-sphenoidal surgery. Early diagnosis and effective treatment is
      important to reverse the acromegalic cardiomyopathy.

PMID- 17533527
TI  - Right atrial blood cyst with total occlusion of the right coronary artery.
AB  - Cardiac blood cysts are rarely seen in adult patients and in the right atrium.
      The origin of cardiac blood cysts is not understood, and several hypotheses have
      been proposed. We present a rare case of right atrial blood cyst with total
      occlusion of the right coronary artery (RCA). Inflammatory processes may have
      played an important role in the development of the cyst, because infiltration of
      inflammatory cells was observed in the cystic wall. Additionally, total
      obstruction of the proximal RCA indicated that ischemia and/or infarction in the
      right atrium might be related to formation of the cyst.

PMID- 17533528
TI  - The dogma that gadolinium contrast media are less nephrotoxic than iodine agents
      for X-ray angiography is a misconception.

PMID- 17533529
TI  - Thyroid dose during neurointerventional procedures: does lead shielding reduce
      the dose?
AB  - PURPOSE: To assess radiation dose to the thyroid in patients undergoing
      neurointerventional procedures and to evaluate dose reduction to the thyroid by
      lead shielding. METHODS AND MATERIALS: A randomized patient study was undertaken
      to evaluate the dose reduction by thyroid lead shields and assess their
      practicality in a clinical setting. Sixty-five patients attending for
      endovascular treatment of arteriovenous malformations (AVMs) and aneurysms were
      randomized into one of 2 groups a) No Thyroid Shield and b) Thyroid Lead Shield.
      Two thermoluminescent dosimeters (TLDs) were placed over the thyroid gland (1 on
      each side) at constant positions on each patient in both groups. A thyroid lead
      shield (Pb eq. 0.5 mm) was placed around the neck of patients in the thyroid lead
      shield group after the neurointerventional radiologist had obtained satisfactory
      working access above the neck. The total dose-area-product (DAP) value, number
      and type of digital subtraction angiography (DSA) runs and fluoroscopy time were
      recorded for all patients. RESULTS: Of the 72 patients who initially attended for
      neurointerventional procedures, 7 were excluded due to failure to consent or
      because of procedures involving access to the external carotid circulation. Of
      the remaining 65 who were randomized, a further 9 were excluded due to;
      procedureabandonment, unfeasible shield placement or shield interference with the
      procedure. Patient demographics included mean age of 47.9 yrs (15-74), F:M=1.4:1.
      Mean fluoroscopy time was 25.9 min. Mean DAP value was 13,134.8 cGy x cm(2) and
      mean number of DSA runs was 13.4. The mean relative thyroid doses were
      significantly different (p< 0.001) between the unshielded (7.23 mSv/cGy2 x 105)
      and shielded groups (3.77 mSv/cGy2 x 105). A mean thyroid dose reduction of 48%
      was seen in the shielded group versus the unshielded group. CONCLUSION:
      Considerable doses to the thyroid are incurred during neurointerventional
      procedures, highlighting the need for increased awareness of patient radiation
      protection. Thyroid lead shielding yields significant radiation protection, is
      inexpensive and when not obscuring the field of view, should be used routinely.

PMID- 17533530
TI  - Thrombin injection for acute hemorrhage following angiography.
AB  - Femoral arterial puncture is the main access for diagnostic and therapeutic
      intervention in vascular disease. Significant complications are unusual and
      include uncontrolled bleeding which usually requires surgery. We report the use
      of ultrasound-guided thrombin injection that prevented any immediate need for
      surgery in 2 cases of uncontrolled bleeding following femoral arteriography.
      Clinical presentations and treatment are reported, together with a review of the
      literature.

PMID- 17533531
TI  - Limitations influencing interventional radiology in Canada: results of a national
      survey by the Canadian Interventional Radiology Association (CIRA).
AB  - PURPOSE: To describe the current state and limitations to interventional
      radiology (IR) in Canada through a large, national survey of Canadian
      interventional radiologists. METHODS: An anonymous online survey was offered to
      members of the Canadian Interventional Radiology Association (CIRA). Only staff
      radiologists were invited to participate. RESULTS: Seventy-five (75) responses
      were received from a total of 247, giving a response rate of 30%. Respondents
      were split approximately equally between academic centers (47%) and community
      practice (53%), and the majority of interventional radiologists worked in
      hospitals with either 200-500 (49%) or 500-1,000 (39%) beds. Procedures listed by
      respondents as most commonly performed in their practice included PICC line
      insertion (83%), angiography and stenting (65%), and percutaneous biopsy (37%).
      Procedures listed as not currently performed but which interventional
      radiologists believed would benefit their patient population included
      radiofrequency ablation (36%), carotid stenting (34%), and aortic stenting (21%);
      the majority of respondents noted that a lack of support from referring services
      was the main reason for not performing these procedures (56%). Impediments to
      increasing scope and volume of practice in Canadian IR were most commonly related
      to room or equipment shortage (35%), radiologist shortage (33%), and a lack of
      funding or administrative support (28%). CONCLUSION: Interventional radiology in
      Canada is limited by a number of factors including funding, manpower, and
      referral support. A concerted effort should be undertaken by individual
      interventional radiologists and IR organizations to increase training capacity,
      funding, remuneration, and public exposure to IR in order to help advance the
      subspecialty.

PMID- 17533532
TI  - Use of nitinol stents following recanalization of central venous occlusions in
      hemodialysis patients.
AB  - PURPOSE: To retrospectively review the patency of endovascular interventions with
      nitinol stent placement for symptomatic central venous occlusions in hemodialysis
      patients. METHODS: A retrospective review of all patients who underwent
      endovascular interventions for dysfunctional hemodialysis grafts and fistulas was
      performed from April 2004 to August 2006. A total of 6 patients presented with
      arm and/or neck and facial swelling and left brachiocephalic vein occlusion. The
      study group consisted of 3 men and 3 women with a mean age of 79.5 years (SD 11.2
      years). Of these 6 patients, 1 had a graft and 5 had fistulas in the left arm.
      The primary indication for nitinol stent placement was technical failure of
      angioplasty following successful traversal of occluded central venous segments.
      Patency was assessed from repeat fistulograms and central venograms performed
      when patients redeveloped symptoms or were referred for access dysfunction
      determined by the ultrasound dilution technique. No patients were lost to follow
      up. RESULTS: Nitinol stent placement to obtain technically successful
      recanalization of occluded venous segments was initially successful in 5 of 6
      patients (83%). In 1 patient, incorrect stent positioning resulted in partial
      migration to the superior vena cava requiring restenting to prevent further
      migration. Clinical success was observed in all patients (100%). Over the follow
      up period, 2 patients underwent repeat intervention with angioplasty alone.
      Primary patency was 83.3% (95% CI 0.5-1.2) at 3 months, and 66.7% at 6 and 12
      months (0.2-1.1, 0.1-1.2). Secondary patency was 100% at 12 months with 3
      patients censored over that time period. Mean primary patency was 10.4 months
      with a mean follow-up of 12.4 months. No complications related to recanalization
      of the occluded central venous segments were observed. CONCLUSION: Our initial
      experience has demonstrated that use of nitinol stents for central venous
      occlusion in hemodialysis patients is associated with good mid-term patency and
      may exceed historical observations with prior use of Wallstents.

PMID- 17533533
TI  - Alcohol ablation therapy of an atypically located symptomatic bronchogenic cyst:
      a case report.
AB  - Bronchogenic cyst is a rare developmental lesion. It is usually asymptomatic and
      most frequently located in the middle mediastinum and lung parenchyma. It can
      cause symptoms only when infected or pressing on neighboring structures. The MRI
      findings in a 34-year-old woman with an 8 months history of back pain were
      evaluated and revealed a cystic lesion in the left paravertebral area. The
      histopathologic evaluation of the material aspirated with CT guidance was
      reported to be bronchogenic cyst. A simultaneous alcohol ablation was
      accomplished. After the procedure the patient's pain disappeared and the follow
      up MRI scan 1 year later revealed no relapse. Paravertebrally located
      bronchogenic cysts are very rare and only 3 cases were found to be reported in
      the medical literature prior to this one. While aspiration alone is sufficient
      for diagnosis, it is insufficient to treat the lesion and prevent the
      recurrences. This paper reports a paravertebral bronchogenic cyst which was
      symptomatic despite of its small size. CT-guided aspiration was accomplished and
      simultaneous alcohol ablation was carried out to prevent recurrences.

PMID- 17533535
TI  - Percutaneous therapy for anastomotic bile leak in liver-transplant patients with
      nondilated bile ducts.

PMID- 17533534
TI  - Cystic echinococcal liver disease: new insights into an old disease and an
      algorithm for therapy planning.
AB  - Human cystic echinococcosis (CE) continues to be a major health problem in
      developing countries. A review of current literature discloses four alternatives
      for the management of active CE, consisting of surgery, percutaneous treatment
      (PT), chemotherapy, and follow-up without intervention, but no clear guidelines
      for directing patients to the different management options. Palliation of
      symptoms or prevention of complications is the main rationale for the treatment
      of CE. Surgery has long been considered as the gold standard treatment. However,
      a meta-analysis comparing the clinical outcomes of patients treated with PT with
      those of a control group treated with surgery found PT to be more effective,
      safer, and cheaper. Medical therapy is considered to be ineffective when the
      criterion of success is defined as the disappearance of the lesion. However,
      medical therapy seems to be effective when the goal of therapy is defined as the
      prevention of complications in asymptomatic patients. We propose an algorithm for
      therapy planning in CE where the first line of therapy for patients with active
      lesions is PT. Patients with lesions unsuitable for PT are directed to surgery if
      they are symptomatic, have complicated lesions or have lesions that are prone to
      rupture. Asymptomatic patients with uncomplicated lesions are directed to medical
      therapy. Medical therapy failures are redirected to surgery.

PMID- 17533536
TI  - Spontaneous rupture of the superficial femoral artery treated with endovascular
      stent-grafting.
AB  - Spontaneous rupture of the superficial femoral artery (SFA) is rare. It may occur
      in the presence of an SFA aneurysm or in a nonaneurysmal, but usually
      atherosclerotic, artery. Previously these ruptures have been treated by surgical
      exclusion, often with bypass grafting. We report a case of spontaneous rupture of
      a nonaneurysmal SFA treated successfully with endovascular stent-grafting.

PMID- 17533537
TI  - Endovascular repair of an anastomotic leak following open repair of abdominal
      aortic aneurysm.
AB  - This report describes the case of an early postoperative anastomotic leak
      following elective open repair of an infrarenal abdominal aortic aneurysm which
      was successfully treated by endovascular stent-grafting. A 71-year-old man
      underwent open tube graft repair of abdominal aortic aneurysm. Twelve days later
      he presented with a contained leak from the distal anastomosis, which was
      confirmed on CT scan. This was successfully treated with a bifurcated aortic
      stent-graft. This case illustrates the usefulness of the endovascular approach
      for resolving this rare surgical complication of open repair of abdominal aortic
      aneurysm and the challenges associated with the deployment of such a device
      within an aortic tube graft.

PMID- 17533538
TI  - Aorto-iliac endovascular reconstruction by kissing stenting through bilateral
      brachial access.

PMID- 17533539
TI  - Radiological interventions for correction of central venous port catheter
      migrations.
AB  - PURPOSE: The purpose of this study was to evaluate radiological-interventional
      central venous port catheter corrections in migrated/malpositioned catheter tips.
      MATERIALS AND METHODS: Thirty patients with migrated/malpositioned port catheter
      tips were included in this retrospective analysis. To visualize the catheter
      patency a contrast-enhanced port catheter series was performed, followed by
      transfemoral port catheter correction with various 5-F angiographic catheters
      (pigtail; Sos Omni), gooseneck snares, or combinations thereof. RESULTS: One
      patient showed spontaneous reposition of the catheter tip. In 27 of 29 patients
      (93%), radiological-interventional port catheter correction was successful. In
      two patients port catheter malposition correction was not possible, because of
      the inability to catch either the catheter tip or the catheter in its course,
      possibly due to fibrin sheath formation with attachment of the catheter to the
      vessel wall. No disconnection or port catheter dysfunction was observed after
      correction. CONCLUSIONS: We conclude that in migrated catheter tips radiological
      interventional port catheter correction is a minimally invasive alternative to
      port extraction and reimplantation. In patients with a fibrin sheath and/or
      thrombosis port catheter correction is often more challenging.

PMID- 17533541
TI  - Staff radiation doses to the lower extremities in interventional radiology.
AB  - The purpose of this study was to investigate the radiation doses to the lower
      extremities in interventional radiology suites and evaluate the benefit of
      installation of protective lead shielding. After an alarmingly increased dose to
      the lower extremity in a preliminary study, nine interventional radiologists wore
      thermoluminescent dosimeters (TLDs) just above the ankle, over a 4-week period.
      Two different interventional suites were used with Siemens undercouch fluoroscopy
      systems. A range of procedures was carried out including angiography,
      embolization, venous access, drainages, and biopsies. A second identical 4-week
      study was then performed after the installation of a 0.25-mm lead curtain on the
      working side of each interventional table. Equivalent doses for all nine
      radiologists were calculated. One radiologist exceeded the monthly dose limit for
      a Category B worker (12.5 mSv) for both lower extremities before lead shield
      placement but not afterward. The averages of both lower extremities showed a
      statistically significant dose reduction of 64% (p < 0.004) after shield
      placement. The left lower extremity received a higher dose than the right, 6.49
      vs. 4.57 mSv, an increase by a factor of 1.42. Interventional radiology is here
      to stay but the benefits of interventional radiology should never distract us
      from the important issue of radiation protection. All possible measures should be
      taken to optimize working conditions for staff. This study showed a significant
      lower limb extremity dose reduction with the use of a protective lead curtain.
      This curtain should be used routinely on all C-arm interventional radiologic
      equipment.

PMID- 17533542
TI  - Percutaneous vein occlusion with small intestinal submucosa: an experimental
      pilot study in Swine and sheep.
AB  - PURPOSE: The objective of this study was to investigate the feasibility,
      outcomes, and amount of small intestinal submucosa (SIS) material needed for
      embolization of jugular vein (JV) in a swine and sheep model. Our hypothesis was
      that SIS would cause vein occlusion. MATERIALS AND METHODS: The external JVs
      (EJV) in swine (n = 6) and JVs in sheep (n = 6) were occluded with SIS fan-folded
      compressed strips. After percutaneous puncture of the peripheral portion of the
      EJV or JV, a TIPS set was used to exit their lumen centrally through the skin.
      The SIS strips were delivered into the isolated venous segment with a pull
      through technique via a 10-Fr sheath. Follow-up venograms were done immediately
      after placement and at the time of sacrifice at 1 or 3 months. Gross examinations
      focused on the EJV or JV and their surrounding structures. Specimens were
      evaluated by histology. RESULTS: SIS strip(s) placement was successful in all
      cases, with immediate vein occlusion seen in 23 of 24 veins (95.8%). All EJVs
      treated with two strips and all JVs treated with three or four strips remained
      closed on 1- and 3-month follow-up venograms. Two EJVs treated with one strip and
      one JV treated with two strips were partially patent on venograms at 1 and 3
      months. There has been one skin inflammatory reaction. Necropsies revealed
      excluded EJV or JV segments with SIS incorporation into the vein wall. Histology
      demonstrated various stages of SIS remodeling with fibrocytes, fibroblasts,
      endothelial cells, capillaries, and inflammatory cells. CONCLUSION: We conclude
      that EJV and JV ablation with SIS strips using percutaneous exit catheterization
      is feasible and effective in animal models. Further exploration of SIS as vein
      ablation material is recommended.

PMID- 17533543
TI  - Pain management during uterine artery embolization for symptomatic uterine
      fibroids.

PMID- 17533544
TI  - Minimally invasive repair of a left ventricular pseudoaneurysm after surgical
      patch reconstruction of an infarct-related free posterior wall rupture: CT-guided
      intervention.
AB  - Ventricular free wall rupture remains the most serious complication after acute
      myocardial infarction. In early-recognized, subacute cases a surgical
      intervention using patches can be lifesaving. However, in the rare case of
      postoperative patch leakage, a relapse of a pseudoaneurysm may occur. This is the
      first case in the literature--to the best of our knowledge--describing a
      minimally invasive strategy using CT fluoroscopic guidance to perform an
      injection of thrombin into the perfused pseudoaneurysm to seal a leakage. This
      therapeutical regimen was chosen--in accordance with cardiac surgeons,
      cardiologists, and interventional radiologists--due to the high risk of adverse
      event after repeated surgery in this particular patient. The follow-up images
      showed complete occlusion of the pseudoaneurysm after the thrombin injection.
      This approach could be discussed in a multidisciplinary setting in similar cases,
      especially due to the described negligible recurrence rate after successful
      initial thrombosis after treating femoral pseudoaneurysms, pseudoaneurysms of the
      pancreatic artery, or even endoleaks after stenting of aneurysms of the aorta.

PMID- 17533545
TI  - Imaging characteristics of Takayasu arteritis.
AB  - Takayasu arteritis is a rare, large-vessel vasculitis in which the nonspecific
      systemic inflammatory symptoms are followed by inflammation of the aorta and its
      major branches. The inflammation of this vessel leads to progressive luminal
      stenosis or aneurysm formation resulting in limb or organ ischemia. Although
      conventional angiography is still accepted as the gold standard modality, the
      information obtained is limited to the vessel lumen. Multidetector computed
      tomographic angiography and magnetic resonance angiography can provide valuable
      information not only regarding intraluminal pathologies but also concerning the
      thickening of the vessel wall, which may be the earliest manifestation of the
      disease.

PMID- 17533546
TI  - Treatment of ureterointestinal anastomotic strictures by diathermal or
      cryoplastic dilatation.
AB  - BACKGROUND: Ureterointestinal anastomotic strictures (UAS) complicate 10-15% of
      surgeries for urinary diversion and are the main cause of deterioration in renal
      function. Treatments are surgical revision, management with autostatic stent,
      balloon dilatation, endoscopic incision, and percutaneous transrenal diathermy
      (Acucise). A new option is cryoplastic dilatation (Polar-Cath). PURPOSE: To
      assess the feasibility, complications, and preliminary results of UAS treatment
      using the Acucise and Polar-Cath systems. METHODS: Nineteen UAS, diagnosed by
      ultrasonography or computed tomography and sequential renal scintigraphy,
      occurred in 15 cancer patients after radical cystectomy and urinary diversion.
      Fifteen were managed with balloon diathermy and 4 by balloon cryoplasty in a
      three-stage procedure--percutaneous nephrostomy, diathermal or cryoplastic
      dilatation, and transnephrostomic control with nephrostomy removal--each
      separated by 15 days. All patients gave written informed consent. RESULTS:
      Dilatations were successful in all cases. The procedure is simple and rapid
      (about 45 min) under fluoroscopic control and sedation. Procedural complications
      occurred in 1 (5%) patient with UAS after Wallace II uretero-ileocutaneostomy: a
      common iliac artery lesion was induced by diathermal dilatation, evident
      subsequently, and required surgical repair. Patency with balloon diathermy was
      good, with two restenoses developing over 12 months (range 1-22) of follow-up.
      With balloon cryoplastic dilatation, one restenosis developed in the short term;
      follow-up is too brief to assess the long-term efficacy. CONCLUSION: Our short
      term results with diathermal and cryoplastic dilatation to resolve UAS are good.
      If supported by longer follow-up, the techniques may be considered as first
      choice approaches to UAS. Surgery should be reserved for cases in which this
      minimally invasive technique fails.

PMID- 17533547
TI  - Palliation of malignant biliary and duodenal obstruction with combined metallic
      stenting.
AB  - PURPOSE: The purpose of this study is to evaluate the efficacy of palliation of
      malignant biliary and duodenal obstruction with combined metallic stenting under
      fluoroscopy guidance. MATERIALS AND METHODS: A retrospective analysis of 9
      patients (6 men and 3 women) who underwent biliary and duodenal stenting was
      performed. The mean age of patients was 61 years (range: 42-80 years). The causes
      of obstruction were pancreatic carcinoma in 7 patients, cholangiocellular
      carcinoma in one, and duodenal carcinoma in the other. Biliary and duodenal
      stents were placed simultaneously in 4 patients. In other 5 patients dudodenal
      stents were placed after biliary stenting when the duodenal obstruction symptoms
      have developed. In two patients duodenal stents were advanced via transgastric
      approach. RESULTS: Technical success rate was 100 %. After percutaneous biliary
      drainage and stenting bilirubin levels decreased to normal levels in 6 patients
      and in remaining 3 patients mean reduction of 71% in bilirubin levels was
      achieved. Tumoral ingrowth occurred in one patient and percutaneous biliary
      restenting was performed 90 days after the initial procedure. Of the 9 patients,
      6 patients were able to tolerate solid diet, whereas 2 patients could tolerate
      liquid diet and one patient did not show any improvement. Mean survival periods
      were 111 and 73 days after biliary and duodenal stenting, respectively.
      CONCLUSION: Combined biliary and duodenal stent placement which can be performed
      under fluoroscopic guidance without assistance of endoscopy is feasible and an
      effective method of palliation of malignant biliary and duodenal obstructions. If
      transoral and endoscopic approaches fail, percutaneous gastrostomy route allows
      duodenal stenting.

PMID- 17533548
TI  - Percutaneous manual aspiration embolectomy of renal vein thrombosis due to acute
      pyelonephritis.
AB  - We report the case of a 50-year-old man who presented to our institution with
      septic thrombosis of the renal vein which had not resolved despite several days
      of antibiotic therapy. Optimal restoration of renal vein flow was obtained by
      percutaneous manual aspiration embolectomy (PMAE) in this patient with
      contraindication to fibrinolytic therapy and surgery.

PMID- 17533550
TI  - Unchanged high prevalence of antibodies to hepatitis E virus (HEV) and HEV RNA
      among blood donors with an elevated alanine aminotransferase level in Japan
      during 1991-2006.
AB  - Hepatitis E is rare in Japan but is occurring more frequently than previously
      thought. To investigate whether de novo subclinical infection of hepatitis E
      virus (HEV) has recently increased in Japan, HEV RNA was assayed in serum samples
      obtained from 4019 Japanese voluntary blood donors with alanine aminotransferase
      (ALT) of > or =61 IU/l, who are likely to have ongoing HEV infection, during 1991
      2006. The overall rates of IgG-class antibody to HEV (anti-HEV IgG), anti-HEV
      IgM/IgA and HEV RNA among 3185 donors in 2004-2006 were comparable with those
      among 594 donors in 1998 (5.3 vs. 5.2%, 0.2 vs. 0.5%, and 0.2 vs. 0.3%,
      respectively). Among blood donors with ALT > or = 201 IU/l in three groups
      according to the year of blood collection (1991-1995 [n = 156], 1996-1999 [n =
      116] and 2004-2006 [n = 61]), there were no appreciable differences in the
      prevalence of anti-HEV IgG (5.8, 4.3, and 6.6%, respectively), anti-HEV IgM/IgA
      (1.9, 3.4, and 3.3%, respectively) and HEV RNA (1.3, 3.4, and 3.3%,
      respectively). The eleven HEV isolates obtained in the present study differed
      from each other by 1.7-22.8% in the ORF2 sequence and segregated into genotype 3
      or 4. The occurrence rate of subclinical infection with divergent HEV strains has
      essentially remained unchanged during 1991-2006 in Japan.

PMID- 17533549
TI  - Contrast-enhanced abdominal angiographic CT for intra-abdominal tumor
      embolization: a new tool for vessel and soft tissue visualization.
AB  - C-Arm cone-beam computed tomography (CACT), is a relatively new technique that
      uses data acquired with a flat-panel detector C-arm angiography system during an
      interventional procedure to reconstruct CT-like images. The purpose of this
      Technical Note is to present the technique, feasibility, and added value of CACT
      in five patients who underwent abdominal transarterial chemoembolization
      procedures. Target organs for the chemoembolizations were kidney, liver, and
      pancreas and a liposarcoma infiltrating the duodenum. The time for patient
      positioning, C-arm and system preparation, CACT raw data acquisition, and data
      reconstruction for a single CACT study ranged from 6 to 12 min. The volume data
      set produced by the workstation was interactively reformatted using maximum
      intensity projections and multiplanar reconstructions. As part of an angiography
      system CACT provided essential information on vascular anatomy, therapy
      endpoints, and immediate follow-up during and immediately after the abdominal
      interventions without patient transfer. The quality of CACT images was sufficient
      to influence the course of treatment. This technology has the potential to
      expedite any interventional procedure that requires three-dimensional information
      and navigation.

PMID- 17533551
TI  - Genome sequence of a Japanese isolate of Radish mosaic virus: the first complete
      nucleotide sequence of a crucifer-infecting comovirus.
AB  - The complete nucleotide sequences of RNA1 and RNA2 of a Japanese isolate of
      Radish mosaic virus (RaMV-J), a crucifer-infecting comovirus, were determined.
      RNA1 is 6064 nucleotides long and encodes a 210-kDa polyprotein containing
      conserved motifs that are required for replication. RNA2 is 4020 nucleotides long
      and encodes a 123-kDa polyprotein containing the putative movement protein and
      two coat proteins. Comparisons of the encoded proteins confirmed that RaMV-J and
      a Czech RaMV isolate are isolates of the same species in the genus Comovirus. A
      phylogenetic analysis of RaMV-J and other comoviruses revealed that legume
      infecting comoviruses constitute a single branch to which RaMV is distantly
      related.

PMID- 17533552
TI  - Characterization of temperature-sensitive Akabane virus mutants and their roles
      in attenuation.
AB  - Akabane virus (AKAV) of the genus Orthobunyavirus in the family Bunyaviridae is
      an important animal pathogen; however, studies on AKAV biology are scarce.
      Therefore, we generated temperature-sensitive (ts) mutants of AKAV in order to
      study its pathogenesis. The ts AKAV mutants were generated by incubating the
      virulent OBE-1 strain with the chemical mutagen 5-fluorouracil. Each ts mutant
      was inoculated intracerebrally into mice to assess its virulence, and the genomic
      sequences of the attenuated mutants were also determined. Three of the twelve ts
      mutants studied showed a mortality rate of less than 10%. Although no mutation
      was detected in the S RNA segment of these three mutants, amino acid
      substitutions were observed in both the M and L RNA segments. Three of the
      mutants and the wild-type virus demonstrated a similar pattern of
      immunoreactivity in an ELISA with anti-Gc monoclonal antibodies. On the other
      hand, using a minireplicon system, the level of L protein activity of each ts
      mutant decreased as the temperature increased. These results suggest that the L
      RNA segment could be involved in the virulence of AKAV, which increases our
      understanding of how the viral gene products contribute to pathogenesis.

PMID- 17533553
TI  - Genetic diversity and recombination of murine noroviruses in immunocompromised
      mice.
AB  - Murine noroviruses (MNV) are newly identified pathogens which infect laboratory
      mice. In this study, we found a high prevalence (64.3%) of MNV in various
      breeding colonies of immunocompromised, transgenic and wild-type mouse lines. All
      mice survived infection with no signs of clinical disease. Faeces samples were
      collected from animals housed in two separate laboratory mouse colonies in
      Berlin, Germany, and screened using quantitative reverse transcription (RT)-PCR.
      We have determined the complete nucleotide sequences of 3 novel MNV strains.
      Furthermore, we sequenced two subgenomic regions within open reading frames
      (ORFs) 1 and 2 that are suitable for genotyping. Sequence analysis of the full
      length and partial genomes obtained from naturally infected mice yielded valuable
      data on genetic diversity of murine noroviruses. The discordance of genotype
      affiliation of some MNVs shown in ORF1 and ORF2 suggests intertypic recombination
      events in vivo.

PMID- 17533555
TI  - Molecular characterization of the surface glycoprotein genes of an H5N1 influenza
      virus isolated from a human in Guangdong, China.
AB  - In March 2006, a human H5N1-infected case was found in Guangdong province, China.
      Here, we molecularly characterized the hemagglutinin (HA) and neuraminidase (NA)
      genes of the A/China/GD01/06 (GD01) strain causing the infection. The
      phylogenetic analyses suggested that the HA and NA genes of GD01 and recent human
      H5N1 viruses from different provinces of China were probably derived from a
      common ancestor and the H5N1 human infection was acquired directly from affected
      poultry. At the cleavage site of HA, GD01 contained multiple basic amino acids, a
      feature characteristic of highly pathogenic avian influenza A viruses. The virus
      possessed Gln222, Gly224, Ser223, Asn182, Gln192 residues adjacent to the
      receptor-binding site, preferential for recognizing SAalpha2, 3Gal. In addition,
      the GD01 NA amino acid sequence possessed Asn344 and Phe466, which might be
      related to the low-pH stability of the sialidase activity and gastrointestinal
      symptoms of the patient.

PMID- 17533554
TI  - Characterization of divergent and atypical canine coronaviruses from Sweden.
AB  - Field canine coronaviruses (CCVs) identified during a series of outbreaks of
      gastroenteritis in Swedish dogs were subjected to genetic analysis involving the
      open reading frame 1b (ORF1b) and the membrane (M) and spike (S) protein genes.
      Four field viruses originating from the Stockholm region presented identical
      sequences and segregated separately from other CCVs characterized so far and from
      GOT/05, the variant recovered in Western Sweden. A recombinant origin of the
      fifth virus identified in the Stockholm region is suggested. In addition, the
      five viruses originating from the same geographical area displayed atypical 5' S
      gene sequences.

PMID- 17533556
TI  - Molecular characterization and detection of Vicia cryptic virus in different
      Vicia faba cultivars.
AB  - After extraction of double-stranded (ds) RNAs from Vicia faba, dsRNA1 and dsRNA2
      of Vicia cryptic virus (VCV), a member of the genus Alphacryptovirus (family
      Partitiviridae), were detected in six out of seven different cultivars by agarose
      gel electrophoresis. In attempts to sequence the complete VCV genome, the dsRNA1
      and dsRNA2 sequences from a total of five different V. faba cultivars were
      determined. Analysis of these sequences indicated that V. faba cultivars contain
      almost indistinguishable VCV sequences. The larger dsRNA1 was 2012 bp in length
      and contained a major open reading frame (ORF) encoding a putative RNA-dependent
      RNA polymerase (RdRp). The smaller dsRNA2 was 1779 bp in length and comprised a
      single ORF on its plus-strand encoding the coat protein (CP). The sequences of
      the dsRNA1 and dsRNA2 ORFs shared highest amino acid sequence identities (84 and
      56%, respectively) with the corresponding gene products of the alphacryptovirus
      white clover cryptic virus 1 (WCCV-1). The 5'-terminal untranslated regions of
      dsRNA1 and dsRNA2 of VCV were highly conserved and were strikingly similar to the
      corresponding regions of WCCV-1. RdRp amino acid sequence alignments revealed
      conserved motifs, which correlate with the phylogenetic clustering of the family
      Partitiviridae.

PMID- 17533557
TI  - A follow-up study of postpartum depressed women: recurrent maternal depressive
      symptoms and child behavior after four years.
AB  - OBJECTIVE: To investigate the prevalence of depressive symptoms and self reported
      health of women who have shown previous postpartum depressive symptoms. To
      examine the behavior of four-year-old children born to mothers affected by
      postpartum depression. METHODS: Longitudinal study. The index group (n = 251)
      constituted of all women with postpartum depressive symptoms on the Edinburgh
      Postnatal Depression Scale (EPDS), in a population-based study made in the late
      1990s. The control group (n = 502) consisted of women without postpartum
      depressive symptoms on the EPDS at the same occasion. Approximately four years
      after delivery these women were asked to answer a short questionnaire on general
      health, the EPDS, and also to assess their child's behavior with the Richman Pre
      School Behaviour Checklist. RESULTS: Women with a history of postpartum
      depressive symptoms were approximately 6 times more likely to have recurrent
      depressive symptoms (OR = 5.82, 95% CI: 3.79-8.93), compared to those without
      postpartum depressive symptoms, and they were also more likely to experience
      physical and mental illness. Although postpartum depressive symptoms in the
      mothers were involved in explaining the likelihood of behavioral problems in
      their four-year-old children, mothers with current depressive symptoms were the
      most likely to have a child with behavioral problems (OR = 4.71, 95% CI: 1.88
      11.78). CONCLUSION: Postpartum depressive illness constitutes a risk for future
      illness as well as maternal perceived behavioral problems in offspring. In order
      to diminish long-term adverse consequences for the mother and the child there is
      a great need to recognize and treat women with postpartum depressive symptoms as
      early as possible.

PMID- 17533558
TI  - Co-occurrence of eating disorders and alcohol use disorders in women: a meta
      analysis.
AB  - This meta analysis involved 41 studies published between January of 1985 and May
      of 2006, which examined the co-occurrence of eating disorders (ED) and alcohol
      use disorders (AUD) in women. Studies were reviewed and a quantitative synthesis
      of their results was carried out via the calculation of standardised effect
      sizes. Direction and strength of the relationships between AUD and specific
      disordered eating patterns were examined. Heterogeneity of reported results was
      also assessed and examined. Only 4 out of 41 studies reported negative
      associations between ED and AUD. The magnitude of the associations between eating
      disordered patterns and AUD ranged from small to medium size and were
      statistically significant for any ED, bulimia nervosa (BN)/bulimic behavior,
      purging, binge eating disorder (BED) and eating disorders not otherwise specified
      (EDNOS). No association was found between anorexia nervosa (AN) and AUD. The
      magnitude of the association between BN and AUD was the most divergent across
      studies and those between each of BED and dietary restriction and AUD were the
      most consistent across studies. Reported associations of different patterns of
      disordered eating and AUD were generally weakest and most divergent when
      participants were recruited from clinical settings and strongest and most
      homogeneous when participants were recruited from student populations.

PMID- 17533559
TI  - [Hartvig Dahl--the lonely rider].

PMID- 17533560
TI  - [Social phobia (social anxiety disorders) in adults and children].

PMID- 17533561
TI  - [Chronically ill--chronically forgotten?--communication/mobility/everyday life].
AB  - In the course of the recent years, the policy for the needs of disabled people
      has started a fundamental paradigm shift. Central elements of the current policy
      for the needs of disabled people are prevention, rehabilitation and integration.
      Self-determination instead of care forms the guiding principle. An indistinct
      definition of chronic disease makes it difficult to obtain a general idea of
      structures in the care and support for people with chronic diseases. The
      following compilation examines requirements in social legislation and questions
      the quality of life by means of the three exemplary aspects: communication,
      mobility and everyday life. Here the question remains whether the current focus
      on health neglects any relevant components of chronic diseases. It turns out that
      people with a chronic illness, although social legislation has improved, are
      neglected the more support they need. Care as an elementary social principle must
      be discussed on an interdisciplinary basis and in the context of the whole
      society.

PMID- 17533562
TI  - [Medical decision making in hospital--results of an exploratory study on the
      value of shared decision making from the physicians point of view].
AB  - The changes in the relationship between doctors and patients and the transfer of
      shared decision making into medical treatment has often been discussed. The role
      and the perspective of the patients are primarily described. The aim of our study
      is to examine the attitudes of physicians regarding the shared decision making
      concept, based on 15 interviews with clinical doctors. Our findings show that
      most doctors know the content of the concept and mostly agree with it. Practical
      barriers for the realisation of shared decision making are often stressed. The
      meaning of the concept of shared decision making for the physicians is in some
      respects different from the meaning of this concept for the patients. It is
      important to examine this concept more particularly with standardised
      instruments. It will be necessary to explore not only the role of patients and
      physicians in the medical decision making process but also the position of other
      relevant persons like the relatives of the patients or the nursing staff.

PMID- 17533563
TI  - [Description of the medical care of younger patients (<65 years) with colorectal
      cancer in Schleswig-Holstein--are diagnostics and therapy compliant with the
      actual S3-guidelines?].
AB  - The Guideline Colorectal Cancer has been existed since 1999. In 2004, a revision
      was published in form of the S3-guideline (number of the AWMF registry: 021/007).
      In this study we aimed to evaluate whether diagnostics and therapy of colorectal
      cancer of younger patients (<65 years) in Schleswig-Holstein (SH) were in
      accordance with the guideline or not. Therefore patients from a molecular genetic
      research project ("popgen") were asked to complete a questionnaire regarding
      their medical care. Data from the self-administered questionnaire and from the
      routine data set of the epidemiological cancer registry SH were available for 245
      patients (mean age: 56.9 years; 48.6% were females). Nearly 54% of the patients
      had a tumour located in the colon and 42.9% in the rectum. Most patients (65.7%)
      experienced locally progressing tumours (T3/T4). Positive lymph nodes were
      diagnosed in 41% of the patients, distant metastases in less than 1%. About 88%
      had a coloscopy, 62.4% an X-ray of the lung, and 78.7% a sonography of the
      abdomen in the course of the preoperative diagnostics. Of all patients, 97.1%
      have been operated. An adjuvant radiation was received by 31.7% and adjuvant
      chemotherapy was given to 36.3% of the patients. In order to assess medical care,
      reference values were defined for specific phrasings from the S3-guideline (e.g.,
      "always indicated": > 95%). According to the data from the patients'
      questionnaires and according to the S3-guideline, quality indicators of the
      preoperative diagnostics in SH were beneath the assumed reference values. But the
      data on therapy procedures indicated a good or at least satisfactory medical
      care.

PMID- 17533564
TI  - [The legal form of "medizinische versorgungszentren"].
AB  - The "Medizinische Versorgungszentrum", established on January 1, 2004, is a new
      service provider within the German health system. With regard to the potential
      legal forms a number of questions remain unanswered. The choice of the legal form
      interacts with the professional code of conduct of the national medical
      association.

PMID- 17533565
TI  - [Burden of acute rotavirus gastroenteritis (RV-AGE) in Germany: a comparison of
      federal statistics and epidemiological data].
AB  - Worldwide, rotavirus (RV) is the main cause for morbidity and mortality due to
      acute gastroenteritis (AGE) among infants and toddlers. In Germany, where RV-AGE
      is notifiable, rotavirus is the most common pathogen of AGE in young children.
      Since 2006, two rotavirus vaccines for use in infants are available. The
      objective of this study is to estimate the burden of RV-AGE among young children
      in Germany on the basis of federal statistics as well as data from epidemio
      logical studies. Between 2001 and 2004, 36,281 (or 37,932) RV infections among
      children below 4 (or 5 years) of age have been notified per year which results in
      an incidence of 1.2%/1%. Epidemiological studies yield an estimate of 117,985
      cases of RV-AGE among children below 4 years of age (incidence: 4%). The hospital
      statistic shows 12,716 RV-AGE cases per year in children below the age of 5 years
      between 2001 and 2004. Those cases account for 22% of all AGE cases. However, the
      causative organism is not stated in more than 75% of cases. In epidemiological
      studies, an average of 53% of the hospitalised cases of AGEs has been attributed
      to RV. Based on these data, 30,500 hospitalized RV-AGE cases can be expected per
      year among children up to 5 years. The mortality statistics show less than one
      death due to RV among young children per year. Based on federal statistics as
      well as epidemiological studies, the burden of RV-AGE can only be estimated
      approximately. While federal statistics underestimate the burden of RV-AGE, the
      burden documented in epidemiological studies in young children is high in
      Germany. These findings support the recommendation of the Deutsche Akademie fur
      Kinderheilkunde und Jugendmedizin (DAKJ) for a general vaccination of against RV
      in Germany.

PMID- 17533566
TI  - [Hygiene ranking in residential homes for the aged in Frankfurt--conception and
      first results].
AB  - Public health departments are obliged by law to survey hygienic procedures and
      condition in residential homes for the aged. Based on the annual hygiene control
      visits, a standardised hygiene ranking was established with the aggregation of
      more than 60 detailed single observations in the following fields: building,
      organisation, training of the staff, actual hygiene situation, repeated deficits,
      food and kitchen hygiene, and drinking water. This hygiene ranking enables not
      only intra-institutional comparisons in different years but also the comparison
      between different homes. The data obtained in 2004 to 2006 demonstrated that this
      method was very well accepted by the institutions and was readily appreciated as
      a tool for external quality assessment.

PMID- 17533567
TI  - [Implementation of the 9th revision of medical licensing regulation for
      physicians in the cross-sectional area "prevention and health promotion" at the
      German medical faculties].
AB  - The coming into effect of the 9th Revision of German Medical Licensing
      Regulations for Physicians on October 1st 2003 saw prevention and health
      promotion become a cross-sectional module of medical training subject to
      compulsory assessments and a grading system. The individual medical faculties are
      responsible for content and teaching methods. An initial survey of all 36 German
      medical facilities shows the current implementation of the new cross-sectional
      area. In a partly standardised questionnaire these faculties were surveyed on the
      linking of coordination and realisation, the didactic methodology concept of
      teaching as well as potentials and difficulties in implementation. The
      implementation of the cross-sectional area differs in responsibility with regard
      to coordination and content, time provided, integration of practice in health
      care and forms of assessment. Whereas consensus exists regarding the relevance
      and integration of preventive themes in teaching, the picture for health
      promotion is very heterogeneous.

PMID- 17533568
TI  - [Long-term follow-up of oral language development in children with permanent
      bilateral hearing loss].
AB  - OBJECTIVE: The aim of this study was to assess the oral language development of
      children with permanent bilateral hearing loss without additional disabilities
      longitudinally (5 time points t1-t5). METHOD: The present follow-up study
      evaluated both receptive and expressive language developmental quotients (DQ;
      desired value 1.0) with standardised developmental scales and receptive and
      expressive vocabulary size with standardised tests (results in T-scores; m=50,
      SD=10). Mean follow-up duration was 38.1 (SD 4.8) months. SAMPLE: A cohort of
      n=18 sensorineural hearing-impaired children was recruited from the German
      Gottinger Hor-Sprachregister. Mean diagnosis age was 21.4 (SD 16.6) months and
      mean age of amplification with hearing aids was 21.7 (SD 16.5) months. RESULTS:
      The mean DQs slowly increased from t1 to t4 (DQ receptive 0.37/0.48/0.55/0.56; DQ
      expressive: 0.51/0.51/0.55/0.55) and remained norm deviant. The diagnosis age of
      hearing loss and both the developmental quotients for receptive (-0.41/-0.42/
      0.53; p<0.05/-0.80; p<0.01) and expressive language (-0.77; p<0.01/-0.55; p<0.05/
      0.66; p<0.01/-0.79; p<0.01) were significantly correlated. The mean receptive
      vocabulary size apparently increased and came up to the lower norm range (29.6
      34.2-43.8), however the mean expressive vocabulary remained far below the norm
      (26.8-29.8). Children with a hearing loss from 71-90 dB scored on average mostly
      higher than children with a loss > 90 dB who all had received a cochlear-implant
      up to t3. Children who were identified as hearing-impaired before the age of 18
      months exhibited on average generally greater DQs. CONCLUSION: The individual
      best available amplification of hearing loss did not compulsively cause an age
      adequate spoken language development, at least not in case of a hearing loss > 40
      dB. So a newborn hearing screening must be the first step in identification,
      intervention and habilitation of an infant with hearing loss. Use of a cochlear
      implant seemed to have a great impact on the oral language development of
      children with a bilateral loss > 90 dB.

PMID- 17533569
TI  - [3rd Workshop on Epidemiology, Prevention and Treatment of Invasive Meningococcal
      Disease in Wurzburg 2006].
AB  - On October 5th, 2006, the German Reference Centre for Meningococci (NRZM) held
      the 3rd Workshop on Epidemiology, Prevention and Treatment of Invasive
      Meningococcal Disease, in collaboration with the German Society for Hygiene and
      Microbiology (DGHM). Given the recent recommendation of the German Standing
      Committee on Vaccination (STIKO) for conjugate meningococcal C vaccination of all
      children in the second year of life, observations from meningococcal C conjugate
      vaccination campaigns in other European countries were presented and compared to
      the German situation. Moreover, the newly implemented cluster detection routines
      employed at the NRZM and their integration into the interactive geographical
      information system EpiScanGIS were shown. Based on recent experiences from
      regional outbreaks in Oberallgau, Sangerhausen, and Greater Aachen, examples for
      public health intervention were given at the conference. In addition, current
      developments in the area of meningococcal research, as well as trends in
      antimicrobial susceptibility were covered. Finally, the latest evidence
      concerning the clinical management and chemoprophylaxis of this invasive
      bacterial disease was discussed.

PMID- 17533572
TI  - Endocrinology of adipose tissue - an update.
AB  - Adipose tissue is the body's largest repository of energy and it plays an
      important role in total energy homeostasis. Moreover, it is now well recognized
      as an endocrine organ. A wide range of different factors including complex
      proteins as well as fatty acids, prostaglandins, and steroids are either
      synthesized de novo or converted in adipose tissue and released into the blood
      stream. These so-called adipokines contribute to the development of obesity
      related disorders, particularly type-2 diabetes (T2D) and cardiovascular disease.
      In this review, we present an overview on the endocrine functions of adipose
      tissue with a special focus on discoveries reported within the past 5 years.

PMID- 17533573
TI  - ApoA-I-binding protein (AI-BP) and its homologues hYjeF_N2 and hYjeF_N3 comprise
      the YjeF_N domain protein family in humans with a role in spermiogenesis and
      oogenesis.
AB  - The screening for additional human YjeF_N domain containing proteins beside the
      apolipoprotein A-I interacting protein (AI-BP), identified two other genes
      designated hYjeF_N2-15q23 (formerly human homologue of yeast edc3) and hYjeF_N3
      19p13.11 comprising the human YjeF_N family. AI-BP is ubiquitously expressed,
      with a predominance of these tissues where the homologues were found to be
      restricted including brain, mammary gland, testes and ovaries.
      Immunohistochemistry of human testes and ovaries showed an expression of hYjeF_N3
      19p13.11 only in Leydig cells and theca cells, respectively, indicating a role in
      steroid hormone metabolism. Interestingly, the protein was also strongly
      expressed in Leydig cell tumors and in thecofibromas. The identification of
      hYjeF_N2-15q23 in theca cells and granulosa cells in ovaries, in human spermatids
      of meiotic division part II and the apical membrane of Sertoli cells in testes
      suggest similar functions in oogenesis and sperm maturation which is strengthened
      by the identification of the spermatogenesis regulator HMGA1 as a conserved
      transcription factor. However, in contrast to AI-BP, both homologous proteins are
      unable to bind apoA-I. These results relate the human YjeF_N domain containing
      protein family to cholesterol processing and steroid hormone metabolism in
      spermiogenesis and oogenesis, and AI-BP may link this function to the HDL
      pathway.

PMID- 17533574
TI  - Alterations of pancreatic beta-cell mass and islet number due to Ins2-controlled
      expression of Cre recombinase: RIP-Cre revisited; part 2.
AB  - Tissue-specific disruption of genes by targeted expression of Cre recombinase in
      insulin-producing cells has been widely used to explore pathways involved in
      regulation of pancreatic beta-cell mass. One particular line of transgenic mice
      [B6.Cg-Tg(Ins2-cre)25Mgn/J], commonly called RIP-Cre, in which the expression of
      Cre recombinase is controlled by a short fragment of the rat insulin II gene
      promoter has been used on at least 20 genes in at least 27 studies. In the
      majority of these studies (15 out of 27) inactivation of the gene of interest was
      associated with alterations in islet architecture, islet mass, or pancreatic
      insulin content. We have tested the hypothesis that genomic integration or
      expression of Cre recombinase alone causes alterations of beta-cell mass by
      quantifying islet number and mass in RIP-Cre mice. We have observed a significant
      hypoplasia of beta-cells in young RIP-Cre mice, and a significant hyperplasia of
      islets in older RIP-Cre animals. These findings suggest that glucose intolerance
      and impaired insulin secretion previously described for younger RIP-Cre mice
      might be caused by transgene-associated islet hypoplasia, and that hyperplasia in
      older mice might reflect a compensatory response to transgene-related glucose
      intolerance.

PMID- 17533575
TI  - Insulin sensitivity and beta-cell function in healthy cats: assessment with the
      use of the hyperglycemic glucose clamp.
AB  - A hyperglycemic clamp (HGC) was developed for use in conscious cats. In 21
      healthy, normal glucose tolerant cats glucose disposal rate (M), insulin
      sensitivity (ISI (HGC)), and beta-cell response (I) at arterial plasma glucose of
      9 mmol.l (-1) were measured. The HGC was tolerated well and steady state glucose
      infusion was achieved. Compared to values reported for humans, M values for the
      cats were low, which appeared to relate to both a low ISI (HGC) and a low I. HGC
      measures correlated with fasting plasma glucose and insulin concentrations as
      well as with their HOMA (homeostasis model assessment) and QUICKI (quantitative
      insulin sensitivity check index) counterparts. Also, I and ISI (HGC) correlated
      with their counterparts derived from intravenous glucose tolerance tests. In
      conclusion, this is the first report of hyperglycemic glucose clamping in cats.
      The procedure (HGC) allows for measurements of glucose disposal, beta-cell
      response and insulin sensitivity. Compared to human data, both insulin
      sensitivity and insulin secretion appeared to be low in cats. This is compatible
      with the carnivorous nature of this species, for which insulin resistance would
      be advantageous during periods of restricted food availability.

PMID- 17533576
TI  - Ginsenoside Rh2 is one of the active principles of Panax ginseng root to improve
      insulin sensitivity in fructose-rich chow-fed rats.
AB  - Ginsenoside Rh2, one of the ginsenosides contained in the Panax ginseng root, was
      employed to screen the effect on insulin resistance of rats induced by a diet
      containing 60% fructose. Single intravenous injection of ginsenoside Rh2
      decreased the plasma glucose concentrations in 60 minutes in a dose-dependent
      manner from 0.1 mg/kg to 1 mg/kg in rats with insulin resistance induced by
      fructose-rich chow. Repeated intravenous injection of ginsenoside Rh2 (1 mg/kg
      per injection, 3 times daily) into rats which received fructose-rich chow for 3
      consecutive days decreased the value of glucose-insulin index, the product of the
      areas under the curve of glucose and insulin during the intraperitoneal (i.p.)
      glucose tolerance test. This means that ginsenoside Rh2 has an ability to improve
      insulin action on glucose disposal. The plasma glucose lowering action of
      tolbutamide, induced by the secretion of endogenous insulin, is widely used to
      characterize the formation of insulin resistance. Time for the loss of plasma
      glucose lowering response to tolbutamide (10 mg/kg, i.p.) in rats during insulin
      resistance induction by fructose-rich chow was also markedly delayed by the
      repeated treatment of ginsenoside Rh2, as compared to the vehicle-treated
      control. Thus, the repeated treatment of ginsenoside Rh2 delayed the development
      of insulin resistance in high fructose feeding rats. Increase of insulin
      sensitivity by ginsenoside Rh2 was further identified using the plasma glucose
      lowering action of exogenous insulin in streptozotocin-induced diabetic rats (STZ
      diabetic rats). Repeated injection of ginsenoside Rh2 at the same dosing (1
      mg/kg, 3 times daily) into STZ-diabetic rats for 10 days made an increase of the
      responses to exogenous insulin. Taken together, it can be concluded that
      ginsenoside Rh2 has an ability to improve insulin sensitivity and it seems
      suitable to use ginsenoside Rh2 as an adjuvant for diabetic patients and/or the
      subjects wishing to increase insulin sensitivity.

PMID- 17533577
TI  - Differential T4 degradation pathways in young patients with preterminal and
      terminal renal failure.
AB  - INTRODUCTION: The aim of this study is to analyze thyroid hormone parameters in
      large homogenous patient cohorts with preterminal (stage 4) and terminal (stage
      5) renal failure in an area of low iodine intake. PATIENTS AND METHODS: Thyroid
      parameters were measured in healthy controls (n=48), patients with preterminal
      renal failure (n=48) and patients with terminal renal failure undergoing
      hemodialysis (n=288). All patients were assessed by measurement of TSH, T4, T3,
      fT4, rT3, Tg and TPO-antibodies. RESULTS: There was a significant decrease of T4
      and fT4 from healthy controls to patients with preterminal renal failure and to
      patients with terminal renal failure. T3 showed a decrease from healthy controls
      to patients with preterminal renal failure and to patients with terminal renal
      failure (1.54+/-0.06 microg/l VS. 1.05+/-0.05 microg/l VS. 1.09+/-0.23 microg/l,
      p<0.001 VS. controls). rT3 was significantly decreased in patients with terminal
      renal failure (0.24+/-0.01 microg/l VS. 0.25+/-0.02 microg/l VS. 0.16+/-0.01
      microg/l, p<0.001). The rT3/T3 ratio was significantly elevated in patients with
      preterminal renal failure (p<0.01). TSH concentrations were in the normal range
      in all groups. CONCLUSION: Our data suggest different T4 degradation pathways in
      patients with preterminal and terminal renal failure.

PMID- 17533578
TI  - Characterization and transcriptional regulation of the human somatostatin
      receptor subtype 1 gene.
AB  - Somatostatin (SRIF) exerts inhibitory effects on virtually all endocrine and
      exocrine secretions. At least five distinct human SRIF receptors have been
      identified ( SST1-SST5). Analysis of the promoter region may provide tools to
      understand transcriptional regulation of SSTS in various tissues, indicating
      specific functions. Transcriptional regulation of the human SST1 was analyzed in
      the present study. Total RNA from a human somatotropic pituitary tumor was
      reverse transcribed. 5'cDNA regions of the human SST1 were cloned using an
      adapted inverse PCR method. Among the 15 PCR clones analyzed, 9 demonstrated an
      extended 5'-utr of 266 nucleotides, determining a thymidine residue as a major
      transcription start site. No introns were evident in the 5'-utr region. The
      promoter region lacked consensus sites for TATA or CAAT boxes, YY1, or an
      initiator sequence, but contained two CpG islands. Different lengths of 5'
      flanking regions cloned by PCR were placed upstream of the luciferase reporter
      gene and transiently transfected into various cell lines. The 2834 nt of the
      promoter region directed significant transcriptional activity in a somatotropic
      pituitary cell line, but neither in COS-7 monkey kidney cells nor in AtT-20
      murine corticotrope cells. Transcriptional activity was not affected by
      incubation with various hormones. Several putative transcription factor binding
      sites inducing the cell-type specific activity were identified.

PMID- 17533579
TI  - Inverse relationship between serum levels of interleukin-1beta and testosterone
      in men with stable coronary artery disease.
AB  - OBJECTIVES: To examine the relationship between serum levels of inflammatory
      cytokines and testosterone in men with stable coronary artery disease (CAD).
      Evidence supports a beneficial effect of testosterone upon objective measures of
      myocardial ischaemia in men with CAD, and in animal models of atherosclerosis.
      Inflammatory cytokines are involved in many stages of the atherosclerotic
      process, however, the effect of testosterone upon inflammatory cytokines within
      the cardiovascular system is largely unknown. METHODS: Serum was collected from
      69 men (59+/-1 years) having >75% occlusion of 1, 2, or 3 coronary arteries.
      Levels of total testosterone (TT), bioavailable testosterone (BT), tumour
      necrosis factor-alpha (TNFalpha), interleukin (IL)-1-beta (IL-1beta), IL-6 and IL
      10 were measured and analysis made between men with 1, 2, or 3 vessel CAD, and
      between men with hypogonadal, borderline hypogonadal and eugonadal serum levels
      of testosterone. RESULTS: In patients with 1, 2, or 3 vessel CAD, significant
      stepwise increases were observed in levels of IL-1beta: 0.16+/-0.03, 0.22+/-0.06,
      and 0.41+/-0.08 pg/ml (p=0.035), and IL-10: 0.93+/-0.11, 1.17+/-0.14, and 2.94+/
      0.65 pg/ml (p=0.008). A significant stepwise increase in levels of IL-1beta was
      also observed in eugonadal, borderline hypogonadal, and hypogonadal men: 0.19+/
      0.05, 0.29+/-0.05, and 0.46+/-0.13 pg/ml (p=0.047). CONCLUSION: Consequently this
      data implicates IL-1beta and IL-10 in the pathogenesis of CAD and suggests that
      testosterone may regulate IL-1beta activity in men with CAD.

PMID- 17533580
TI  - Effect of telmisartan on cholesterol levels in patients with hypertension - Saga
      Telmisartan Aggressive Research (STAR).
AB  - Saga Telmisartan Aggressive Research (STAR) is a single-arm, prospective multi
      center trial to evaluate the effectiveness of treatment with telmisartan in
      patients with hypertension. A total of 197 patients with a systolic blood
      pressure of > or =140 or a diastolic blood pressure of > or =90 mmHg were
      enrolled in this study, and were prescribed 20 to 80 mg/day of telmisartan for 6
      months. In all patients, both systolic and diastolic blood pressures decreased
      (159+/-20 to 135+/-12 mmHg, p<0.0001, 87+/-12 to 75+/-8 mmHg, p<0.0001,
      respectively). In addition, total cholesterol (TC) levels decreased from 200+/-40
      to 188+/-33 mg/dl (p<0.05). In patients with TC > or =220 mg/dl, the change was
      more striking (249+/-33 to 204+/-31 mg/dl, p<0.0001). Even in patients receiving
      statins, TC levels still were decreased (216+/-51 to 190+/-31 mg/dl, p<0.02). In
      addition, TC levels were also decreased even in patients receiving telmisartan in
      exchange for other ARBs with TC > or =220 mg/d. Triglyceride (TG) levels were
      decreased (270+/-199 to 175+/-74 mg/dl, p<0.005) in patients with TG levels > or
      =150 mg/dl. Fasting blood glucose (FBG) was decreased (158+/-68 to 138+/-60
      mg/dl, p<0.05) in patients with FBG > or =110 mg/dl. These results suggest that
      telmisartan may have favorable effects on lipid and glucose metabolism, in
      addition to lowering blood pressure. The profound effect of telmisartan to lower
      cholesterol suggests a potential use in hypertensive patients with dyslipidemia.

PMID- 17533581
TI  - Plasma adiponectin is increased in mice selectively bred for high wheel-running
      activity, but not by wheel running per se.
AB  - Mice selectively bred for high wheel-running activity (S) have decreased fat
      content compared to mice from randomly bred control (C) lines. We explored
      whether this difference was associated with alterations in levels of circulating
      hormones involved in regulation of food intake and energy balance, and whether
      alterations were caused by the presence of a running wheel. Plasma levels of
      leptin, adiponectin, and corticosterone as well as body composition were analyzed
      in male S mice housed with (+) and without (-) access to running wheels at ages
      of 10 and 18 months. These levels were compared to those found in C+ mice. Plasma
      corticosterone did not differ among groups. While plasma leptin levels tended to
      be lower in S+ mice as compared to S- or C+ mice, these differences were largely
      attributable to differences in fat content. Adiponectin levels were increased in
      S mice (+60%) compared to C mice, irrespective of wheel access. High levels of
      this hormone may be a trait co-segregated in mice bred for high wheel-running
      activity.

PMID- 17533582
TI  - Metabolic stress with a high carbohydrate diet increases adiponectin levels.
AB  - BACKGROUND: Adiponectin is an adipose tissue-specific protein, which possesses
      anti-atherogenic and antidiabetic properties, yet its plasma levels are decreased
      in subjects with metabolic syndrome. Although high fat diet has been linked to
      hypoadiponectinemia, the effect of high-carbohydrate diet on adiponectin levels
      is not known. Therefore, we studied the effect of high-carbohydrate diet on
      adiponectin levels in the rat models of hypertension and insulin resistance.
      METHODS: Rats were randomly assigned to the high carbohydrate diet [Sprague
      Dawley rats with fructose enriched diet (SDR-F) and spontaneously hypertensive
      rats with sucrose enriched diet (SHR-S model)] or chow diet (Control group). Rats
      were followed for 6 weeks (SDR-F model) and 8 weeks (SHR-S model). Body weight,
      systolic blood pressure, plasma levels of glucose, insulin, triglycerides and
      adiponectin, were recorded. RESULTS: Both models were associated with features of
      the metabolic syndrome, namely, high insulin levels, increased blood pressure and
      triglyceride levels. Plasma adiponectin levels did not change in the control
      groups. In contrast, adiponectin levels increased by 39 and 30% compared to
      baseline following four and six weeks of fructose enriched diet in SDR (from
      3.3+/-0.2 to 4.5+/-0.4 and 4.3+/-0.2 microg/ml, respectively, p<0.05). Likewise,
      five and eight weeks of sucrose enriched diet in SHR, induced a 54 and 81%
      increase in adiponectin levels compared to baseline (from 4.2+/-0.3 to 6.3+/-0.3
      and 7.3+/-0.5 microg/ml, respectively, p<0.01). CONCLUSION: Metabolic stress with
      a high-carbohydrate diet increases plasma levels of adiponectin. Further studies
      will elucidate whether this is a transitory compensatory mechanism or a sign of
      target organ resistance to adiponectin.

PMID- 17533583
TI  - Effects of solid versus liquid meal-replacement products of similar energy
      content on hunger, satiety, and appetite-regulating hormones in older adults.
AB  - OBJECTIVE: To examine whether solid versus liquid meal-replacement products
      differentially affect appetite and appetite-regulating hormones in older adults.
      METHODS: On two occasions, 9 subjects (age: 61+/-3 years; BMI: 25.6+/-1.3 kg/m
      (2)) consumed 25% of daily energy needs as solid or liquid meal-replacements of
      similar energy contents. Blood and appetite ratings were collected over 4 hours.
      RESULTS: The post-prandial hunger composite (area under the curve) was lower
      following the solid versus liquid meal-replacement (p<0.005) and remained below
      baseline over 4 hours (p<0.05). Similar responses were observed with the desire
      to eat. The insulin and ghrelin composites were lower following the solid trial
      compared to the liquid [insulin: 5825 (range: 4676-11639) VS. 7170 (4472-14169)
      uIU/l x 240 min, p<0.01; ghrelin: -92798 (range: -269130-47528) VS. -56152
      (range: -390855-30840) pg/ml x 240 min, p<0.05]. Ghrelin also remained below
      baseline over 4 hours (p<0.05). No differences in cholecystokinin and leptin were
      observed between products. CONCLUSION: The consumption of comparable meal
      replacement products in solid versus liquid versions with similar energy contents
      led to differential appetitive responses and should not be viewed as dietary
      equivalents in older adults.

PMID- 17533584
TI  - Genetic variation in two proteins of the endocannabinoid system and their
      influence on body mass index and metabolism under low fat diet.
AB  - The endocannabinoid system (ECS) plays an important and not yet fully understood
      role in hypothalamic and peripheral regulation of food intake, obesity, and
      metabolism. Two frequent single nucleotide polymorphisms (snp) have been
      identified in members of the ECS: the 1359 G/A variant in the cannabinoid
      receptor 1 ( CB1) and the P129T polymorphism in fatty acid amide hydrolase (
      FAAH), a key degradation enzyme of endocannabinoids. -While for the 1359 G/A
      variant an association has been shown only with psychiatric diseases such as drug
      abusing schizophrenia, the P129T polymorphism has recently been proved to be
      correlated to a higher body mass index (BMI) in a group of black and white
      Americans. However, no knowledge exists as to whether these variants affect the
      outcome of a low fat diet in obese subjects. Therefore, we genotyped a group of
      451 obese and dyslipidaemic participants and observed the biometric and metabolic
      outcome of a 6 week low fat diet. While no significance was seen for the 1359 G/A
      variant, carriers of the P129T mutation in FAAH had a significantly greater
      decrease in triglycerides and total cholesterol as compared to wild type. The
      reason for our findings remains to be elucidated, however, a hepatic
      downregulation of endocannabinoid tone may contribute to the observed outcome in
      studied subjects.

PMID- 17533585
TI  - Relative hypoleptinemia in poorly controlled patients with type 1 diabetes.

PMID- 17533587
TI  - The effect of stem cell mobilisation with granulocyte colony-stimulating factor
      on the morphology of the haematopoietic organs in mice.
AB  - The cellular mobilisation of mice with granulocyte colony-stimulating factor (G
      CSF) results in an egress of haematopoietic stem/progenitor cells from the bone
      marrow and an increase in their level in the peripheral blood. While the
      mobilisation process with different agents is widely studied, little is known
      about the morphology of the murine haematopoietic organs during the mobilisation.
      The purpose of this study was to examine the morphology of the bone marrow,
      spleen and liver in mice mobilised with G-CSF. To address this issue mice were
      injected subcutaneously with G-CSF for 6 consecutive days. Morphological analysis
      revealed an increase in the number of mature neutrophils close to the wall of
      sinusoids in the bone marrow as well as hypertrophy of the red pulp in the
      spleen. At the same time no morphological changes were noticed in the livers of G
      CSF-mobilised mice. In conclusion, G-CSF induces discrete ultrastructural changes
      in the bone marrow, which intensify the transendothelial traverse of
      haematopoietic stem and progenitor cells from it. The changes in the spleen are
      related to repopulation of this organ by mobilised early haematopoietic cells
      circulating in the peripheral blood. We also noticed that the process of
      migration of haematopoietic cells from the bone marrow into the peripheral blood
      began on day 2 and was most pronounced on day 4 after stimulation with G-CSF.

PMID- 17533586
TI  - [Treatment of fibrous dysplasia].
AB  - BACKGROUND: The fibrous dysplasia is a rare disease of bone metabolism. Most
      common on the extremities, its appearance at the skull base is rare but of
      importance in clinical otorhinolaryngology. The patients suffer from problems
      such as cosmetical limitation, recurrent pain and in later phases from functional
      losses which result from bone dysplasia. METHODS: Based on the experiences of
      these cases and the study of the current literature we would like to suggest a
      stage dependent therapy concept that includes conservativ options as well as
      surgical methods which are divided into curative and palliative surgical
      treatments. PATIENTS: The Department of Otorhinolaryngology in Bochum has been
      involved in the therapy of eight patients suffering from fibrous dysplasia which
      have been treated and examined from six to twenty years. RESULTS: Treatment in
      fibrous dysplasia can be efficient in increasing quality of life. A complete
      healing is rare and not the main target of treatment. CONCLUSIONS: The staged
      therapy of fibrous dysplasia consists of conservative and surgical treatment and
      the combination of both. The decision for an individual therapy concept might be
      difficult and often requires close interdisciplinary cooperation.

PMID- 17533588
TI  - The fine structural organization of the olfactory epithelium of Cyprinus carpio
      (Linnaeus): a scanning electron microscopic study.
AB  - The fine anatomical structures of the olfactory epithelium of Cyprinus carpio
      (Linnaeus) have been systematically studied with the help of the scanning
      electron microscope (SEM). The olfactory rosette is an oval structure composed of
      a number of lamellae arranged on a median raphe. A large part of the lateral
      surface of the rosette is covered with non-receptor epithelium, whereas the
      receptor epithelium occupies a much smaller area in the middle part. The
      nonreceptor epithelium is covered with a tuft of ciliated supporting cells, among
      which the stratified epithelial cells and mucous cells are located. The receptor
      epithelium is represented by the flagellated and microvillus receptor and
      supporting cells. Different cells on the olfactory epithelium correlate with the
      functional significance of the fish concerned.

PMID- 17533589
TI  - Superficial veins of the foot in the baboon Papio anubis.
AB  - Although the baboon is considered a good animal model in biomedical research, no
      description of the superficial veins of the foot in Papio anubis is found in the
      available literature. The current study was conducted to document the anatomy of
      these veins in the baboon foot. A macroscopic anatomical investigation was
      carried out on 20 hind legs (10 cadavers) of the adult Papio anubis (9 males and
      1 female). The circulatory system of the entire body was filled with coloured
      latex. Traditional methods were used for the preparation of the veins of the
      legs. These were then compared with the venous system of the lower extremities in
      humans as presented in the literature. The medial and lateral metatarsal veins,
      the dorsal venous network, the long saphenous vein and the short saphenous vein
      in Papio anubis were described according to their origin, course, opening, length
      and diameter. The network observed was divided into three types with respect to
      the connections between the superficial veins. The investigation revealed no
      symmetry in the venous system of the baboon foot. The short saphenous vein
      appeared to be the main vein of the hind leg in Papio anubis and the long
      saphenous vein ran as a double vessel.

PMID- 17533590
TI  - Incidence, types and clinical implications of a non-metrical variant--mylohyoid
      bridging in human mandibles.
AB  - Mylohyoid bridging (MB) is a non-metrical variant of the human mandible. The
      incidence and types of MB were investigated in 264 mandibles (edentulous 116,
      semi-dentulous 90 and dentulous 58). No mandible showed a complete type of MB,
      although 19 (7.2%) mandibles had a partial type. These were classified into two
      subtypes: distal partial (DP; Type I) and proximal partial (PP; Type II),
      depending on their location over the mylohyoid groove. The MB was present
      unilaterally in 7.76% of edentulous mandibles: right side 5.17% (3.45% PP type
      and 1.72% DP type) and left side 2.59% (1.72% PP type and 0.86% DP type). Of the
      semi-dentulous mandibles 3.33% had DP type of MB, 1.11% on the right side and
      2.22% on the left side, and of the dentulous mandibles 1.72% had DP type of MB on
      the right side. A total of 13 mandibles out of 264 (4.92%) had unilateral MB. No
      dentulous mandible had bilateral MB, but 3.45% of edentulous and 2.22% of semi
      dentulous mandibles did have. In total, 6 mandibles out of 264 bones (2.27%) had
      bilateral MB. Of the bilateral incidences 1.72% of edentulous mandibles had a DP
      DP combination and the remaining 1.72% had a PP-DP combination. However, both
      instances of bilateral MB in semi-dentulous mandibles were of PP-DP combination.
      The incidence or types of MB showed no statistically significant differences
      between the groups or sides (p > 0.5; chi(2) test). In conclusion, the complete
      type of MB is a rare occurrence. The incidence increases with age, as edentulous
      mandibles had a higher incidence of MB than the other two groups. Clinically, MB
      may compress the mylohyoid neurovascular bundle, leading to neurological or
      vascular disorders.

PMID- 17533591
TI  - The clinical anatomy of the internal thoracic veins.
AB  - The branching pattern and adequacy of the internal thoracic veins (ITV) are
      important factors, providing useful information on the availability of vessels
      and their appropriateness as an option for anastomoses in plastic and
      reconstructive surgery. During 100 cadaveric examinations of the anterior
      thoracic wall it was observed that ITVs were formed by the venae commitantes of
      ITAs, which united to form a single vein (one for the right side and one for the
      left) draining into the right and left brachiocephalic veins. The tributaries of
      ITVs corresponded to the branches of ITA. The right internal thoracic vein
      bifurcated at the 2(nd) rib in 36% of the specimens, at the 3(rd) rib in 30% of
      the specimens, at the 4(th) rib in 10% of the specimens and in 24% of the
      specimens it remained a single vein. The left internal thoracic vein bifurcated
      at the 3(rd) rib in 52% of specimens, at the 4(th) rib in 20% of specimens and in
      28% of the specimens it remained as a single vein. In addition, it was observed
      that in 78% of specimens ITVs were connected to each other by a venous arch. This
      arch displayed four distinct morphologies: transverse (n = 7), oblique (n = 16),
      U-shaped (n = 51) and double-arched (n = 4). All 78 arches were posterior to the
      xiphisternal joint and no artery accompanied them. In the remaining specimens,
      RITV and LITV exhibited a venous plexus formation. The distance from the sternum
      to ITV gradually decreased as the vessel passed caudally; the diameter of the
      vessel similarly decreased along the vein's caudal course. The frequent
      appearance of two concomitant veins on both sides of the thorax may offer the
      opportunity to reduce venous congestion by two vein anastomoses. More detailed
      knowledge of the anatomy of ITV may prove useful in planning surgical procedures
      in the anterior thorax in order to avoid unexpected bleeding.

PMID- 17533592
TI  - The anatomy of the tendon of the infundibulum revisited.
AB  - The heart is a muscular organ supported by collagenous tissue. The collagenous
      tissue is condensed in certain areas to form a supporting framework, often called
      the fibrous skeleton. The so-called tendon of the infundibulum has previously
      been described as part of this skeleton, but its structure and incidence remain
      ill defined. The tendon was initially described as a strip of fibrous tissue
      running between the aortic root and the pulmonary trunk. Since information on its
      structure is vague, we sought to evaluate its existence in 100 formalin-fixed
      adult human hearts obtained from subjects ranging in age from 22 to 86 years, in
      20 hearts from infants and children aged from 2 months to 6 years at the time of
      their death and in 10 cattle hearts. We used classical macroscopic anatomical
      techniques to demonstrate all the possible connections between the sinuses of the
      aorta and the pulmonary trunk. We then supplemented the macroscopic techniques
      with serial transverse histological sections taken through the vascular roots,
      staining the sections with the haematoxylin-eosin, van Gieson, Masson trichrome
      and orcein staining methods. Fascial bands surrounded by connective tissue were
      observed in all hearts. In 80 adult hearts and in 16 neonatal hearts we found
      fascial bands or strips, which connected the aortic and pulmonary roots. Only in
      two hearts, however, were we able to identify tendon-like structures, and
      histology revealed that these were formed by tightly packed collagen fibres
      intermingled with fat, most likely due to advanced age. Thus in those cases where
      a "tendon" was present it was no more than condensed fascial bands joining
      together the apposing sinuses of the arterial trunks. In our opinion, therefore,
      accounts in the literature describing the "tendon of the infundibulum" as a
      tendinous structure connecting the aortic and pulmonary roots do not accurately
      represent this anatomical structure.

PMID- 17533593
TI  - The clinical significance of the petroclinoid ligament.
AB  - This report describes the topography and structure of the petroclinoid ligament
      with reference to its clinical significance. Observations of this ligament were
      performed on 24 sections of human heads. Remnants of the ossified form of this
      ligament were sought in 73 dry human skulls. It was found that the petroclinoid
      ligament existed as an anterior and posterior fold of the dura mater and
      stretched from the petrous apex and the anterior and posterior clinoid process
      respectively. We assessed the close proximity of this ligament to the oculomotor
      nerve. In one case we found a partially ossified posterior petroclinoid ligament,
      which appeared as a bony spike that arose posteriorly and inferiorly from the
      posterior clinoid process.

PMID- 17533594
TI  - The morphometric study of the amygdala in the rabbit.
AB  - Volumetric measurements of the individual nuclei in the amygdala (CA) of the
      rabbit reveal poor development of the basolateral (BL) and lateral olfactory
      tract (NLOT) and medial (ME) nuclei. On the other hand, the volumes of the
      lateral (LA), basomedial (BM), central (CE) and cortical (CO) nuclei are
      remarkable in this species. A comparison of the densities of neurons in the
      individual nuclei with the mean numerical density of cells in the rabbit CA
      indicates that the densities of neurons in LA, BL and BM are significantly lower
      than the mean (p < 0.05), whereas in CE, CO, ME and NLOT these values are
      significantly higher than the mean (p < 0.05). It should be noted, however, that
      of all the nuclei studied those in CE show the greatest similarity in density to
      CA as a whole. To some extent a similar division of the rabbit CA may be made
      using the size parameters of the amygdaloid neurons as a marker. The large
      neurons populate less densely organised CA areas such as LA, BL and BM, whereas
      the small cells create ME and NLOT, where the neurons are densely arranged. The
      CE and CO occupy intermediate positions, with the neurons similar in size to the
      mean for the total rabbit CA. These morphometric data from CA in the rabbit, when
      compared with the similar data for the common shrew and guinea pig (see our
      previous papers), lead to the conclusion that the amygdalae in all three species
      are very similar with respect to the distribution of neurons in relation to
      density and size and that, when volumetric measurements are taken into account,
      CA in the rabbit is much more similar to that of the guinea pig than that of the
      common shrew.

PMID- 17533595
TI  - The nerve cells of the neostriatum in the common shrew (Sorex araneus) and bank
      vole (Clethrionomys glareolus): a Golgi comparative study.
AB  - The studies were carried out on 12 brains derived from adult representatives of
      two mammalian orders, Insectivora and Rodentia. The neostriatum was compared in
      the common shrew (Sorex araneus) and bank vole (Clethrionomys glareolus). Three
      main types of striatal neuron were distinguished in the common shrew and five
      types of neurons in the bank vole. The fifth type of bank vole neurons was
      additionally divided into two subtypes with respect to dendritic pattern.

PMID- 17533596
TI  - Secular changes in the physical development of students of the Medical University
      of Lodz.
AB  - This study analyses, using selected somatometric features, secular trend changes
      which have occurred over a quarter of a century in female and male students of
      the Medical University of Lodz. The study is based on the results of an
      anthropometric survey carried out among first-year students who commenced their
      studies in the academic years 1978/79 (240 females and 193 males), 1982/83 (347
      females and 188 males), 1988/89 (178 females and 165 males) and 2003/04 (188
      females and 77 males). The following features were examined in all participants
      in the survey: body height (B-v), the height of the lower body segment measured
      from a floor base to the crista iliaca at the point on the mid-axillary line (B
      ic), shoulder width (a-a), intertrochanteric distance (tro-tro) and resting chest
      circumference. To compare average values Student's t-test was used with
      assumptions of equal and unequal variances. To gauge the magnitude of changes in
      specific features in the course of a quarter of a century a percentage difference
      in results was calculated for the years 2003/2004 and 1978/1979. The basis for
      the calculations was the initial value of a feature at the beginning of the
      period analysed. It was determined that in the 25-year period analysed (1978
      2003) the young people commencing studies at the Medical University of Lodz
      exhibited an acceleration in the height of the lower body segment (B-ic) and of
      the intertrochanteric distance (tro-tro) and a deceleration in resting chest
      circumference. Additionally, an increase in shoulder width has been noted in
      female students; no significant intergenerational changes were noted in body
      height, although the last 15 years display certain symptoms of deceleration;
      there is an emerging tendency towards a blurring of the differences in body
      proportions between the sexes in the environment of the young people studying at
      the Medical University of Lodz.

PMID- 17533597
TI  - Vascular anomalies in a case of situs inversus.
AB  - Situs inversus is a developmental condition in which the thoracic and abdominal
      organs fail to negotiate their normal migration patterns and the result is a
      mirror-image arrangement of these viscera. The literature provides evidence that
      individuals with this condition have a higher incidence of other congenital
      malformations (e.g. heart anomalies). Here we describe the dissection of a 71
      year-old female cadaver with situs inversus, in which we discovered multiple
      anomalous vessels associated with the coeliac trunk directed toward the liver. In
      addition, we identified the inferior vena cava on the left side and a persistent
      supracardinal vein on the right, constituting a double inferior vena cava.
      Finally, we identified multiple abnormal venous channels associated with the sub
      renal inferior vena cava. These vascular patterns are indeed a rare finding and
      have surgical implications but may indicate a higher incidence of vascular
      anomalies in cases of situs inversus.

PMID- 17533598
TI  - Arteria lusoria in patients with a normal and a right-sided aortic arch diagnosed
      with multi-slice computed tomography: a report of two cases.
AB  - A retro-oesophageal course of the right subclavian artery is referred to as
      "arteria lusoria". It may be related to severe compression of the trachea and
      oesophagus, typically resulting in impaired swallowing. The paper presents two
      patients with arteria lusoria, which in one patient was an aberrant right
      subclavian artery and in the other an aberrant left subclavian artery,
      originating from the right-sided aortic arch. In both cases the diagnosis was
      made with multi-slice computed tomography. The embryology of the anomalies and
      clinical status of the patients is discussed. Arteria lusoria should be
      considered in differential diagnosis in patients with dyspnoea and dysphagia.
      Multi-slice computed tomography allows this anatomical variant to be reliably
      visualised.

PMID- 17533599
TI  - Type I split cord malformation with an usual bony morphology.
AB  - Variations in the configuration of the bony septum found in patients with split
      cord malformations are rare. We report the seemingly rare occurrence of a midline
      bony septum that ended posteriorly as a fully formed bony spinous process. We
      speculate that this variation is due to misplaced mesodermal cells associated
      with the primitive endomesenchymal tract during approximately the third week of
      foetal life. The clinician that manages these patients may wish to consider this
      rare morphology and avoid excessive manipulation of such a process, which could
      potentially injure an underlying hemicord.

PMID- 17533600
TI  - Retrosplenic course of the transverse cervical artery with the suprascapular
      artery travelling through the suprascapular notch.
AB  - Anatomical variations of the transverse cervical and suprascapular arteries are
      common. We report an adult male cadaver found to harbour an unusual variation of
      the right course of these two arteries. The transverse cervical artery arose
      independently from the first segment of the subclavian artery and passed deep to
      the anterior scalene muscle, a course which, to our knowledge, has not been
      reported before. Simultaneously, the ipsilateral suprascapular artery arose from
      the third segment of the subclavian artery and travelled posteriorly with the
      suprascapular nerve deep to the suprascapular ligament. We believe this is the
      first report of such a simultaneous occurrence.

PMID- 17533614
TI  - Optimized production and concentration of lentiviral vectors containing large
      inserts.
AB  - Generation of high titer lentiviral stocks and efficient virus concentration are
      central to maximize the utility of lentiviral technology. Here we evaluate
      published protocols for lentivirus production on a range of transfer vectors
      differing in size (7.5-13.2 kb). We present a modified virus production protocol
      robustly yielding useful titers (up to 10(7)/ml) for a range of different
      transfer vectors containing packaging inserts up to 7.5 kb. Moreover, we find
      that virus recovery after concentration by ultracentrifugation depends on the
      size of the packaged inserts, heavily decreasing for large packaged inserts. We
      describe a fast (4 h) centrifugation protocol at reduced speed allowing high
      virus recovery even for large and fragile lentivirus vectors. The protocols
      outlined in the current report should be useful for many labs interested in
      producing and concentrating high titer lentiviral stocks.

PMID- 17533615
TI  - Fused donor-acceptor ligands in RuII chemistry: synthesis, electrochemistry and
      spectroscopy of [Ru(bpy)3-n(TTF-dppz)n](PF6)2.
AB  - Three ruthenium(II) polypyridine complexes of general formula [Ru(bpy)(3-n)(TTF
      dppz)n](PF6)2 (n=1-3, bpy=2,2'-bipyridine), with one, two or three redox-active
      TTF-dppz (4',5'-bis(propylthio)tetrathiafulvenyl[i]dipyrido[3,2-a:2',3'
      c]phenazine) ligands, were synthesised and fully characterised. Their
      electrochemical and photophysical properties are reported together with those of
      the reference compounds [Ru(bpy)3](PF6)2, [Ru(dppz)3](PF6)2 and
      [Ru(bpy)2(dppz)](PF6)2 and the free TTF-dppz ligand. All three complexes show
      intraligand charge-transfer (ILCT) fluorescence of the TTF-dppz ligand.
      Remarkably, the complex with n=1 exhibits luminescence from the Ru(2+)-->dppz
      metal-to-ligand charge-transfer ((3)MLCT) state, whereas for the other two
      complexes, a radiationless pathway via electron transfer from a second TTF-dppz
      ligand quenches the (3)MLCT luminescence. The TTF fragments as electron donors
      thus induce a ligand-to-ligand charge-separated (LLCS) state of the form TTF-dppz
      -Ru(2+)-dppz-TTF(+). The lifetime of this LLCS state is approximately 2.3
      micros, which is four orders of magnitude longer than that of 0.4 ns for the ILCT
      state, because recombination of charges on two different ligands is substantially
      slower.

PMID- 17533616
TI  - Fabrication of hexaphenylsilole nanowires and their morphology-tunable
      photoluminescence.
AB  - Immersion of nanoporous alumina membranes into saturated solutions of
      hexaphenylsilole with subsequent solvent evaporation affords aligned organic
      nanowires. The luminescent properties of the hexaphenylsilole nanowires can be
      manipulated by varying their morphologies, which were controlled by changing the
      channel sizes of the alumina templates.

PMID- 17533617
TI  - Single-molecule studies of a model fluorenone.
AB  - Single-molecule fluorescence measurements of 2,7-bis(3,4,5
      trimethoxyphenylethenyl)fluorenone (OFOPV) reveal narrow emission spectra
      concentrated around 540 nm, with weak emission at longer wavelengths. The wide
      scattering of emission-maximum wavelengths is attributed to varying molecular
      environments, with dimers or higher-order aggregates contributing to the low
      energy emission. This spectral distribution indicates that emission from monomers
      of this model fluorenone is mostly green, which is consistent with contaminant
      emission (g-bands) often observed in fluorene- and polyfluorene-based organic
      light emitting diode (OLED) devices. A histogram of center wavelengths from 118
      single-molecule spectra shows good agreement with the green emission previously
      observed in thermally stressed 2,7-bis(3,4,5-trimethoxyphenylethenyl)-9,9
      diethylfluorene (OFPV). Whereas bulk OFPV exhibits blue fluorescence at about 480
      nm, OFOPV bulk thin film measurements reveal red luminescence shifted to 630 nm.
      This unexpected peak position for bulk OFOPV shifts to higher energies (ca. 540
      nm) upon dilution in a solid-state matrix, suggesting that the bulk red emission
      finds its origins in interactions between fluorenone molecules. Explanations for
      this red emission include aggregate or excimer formation or intermolecular energy
      transfer between fluorenone molecules.

PMID- 17533619
TI  - Impact of altered loading conditions on ventricular performance in fetuses with
      congenital cystic adenomatoid malformation and twin-twin transfusion syndrome.
AB  - OBJECTIVES: In the fetus with a structurally normal heart, two conditions--giant
      chest mass, such as congenital cystic adenomatoid malformation (CCAM), and twin
      twin transfusion syndrome (TTTS)--alter ventricular loading conditions and may
      result in cardiovascular compromise. The aim of this study was to elucidate the
      mechanism of cardiovascular dysfunction by comparing geometry-independent,
      Doppler flow-derived measures of ventricular performance in fetuses with altered
      loading conditions vs. those in normal fetuses. METHODS: Doppler flow-derived
      measures of myocardial performance index (MPI) as described by Tei, ventricular
      ejection force as described by Isaaz, and combined cardiac output (CCO) were
      obtained by echocardiography in fetuses with a normal cardiovascular system (n =
      76) or CCAM (n = 36) and fetal partners with TTTS (n = 22). RESULTS: In the CCAM
      group, systolic performance as evidenced by the ejection forces was preserved,
      right ventricular (RV) MPI was increased and CCO diminished, suggesting diastolic
      dysfunction and poor filling secondary to cardiac compression and a tamponade
      effect. In TTTS, recipient twins exhibited greater left ventricular (LV) ejection
      forces and higher CCO than donor twins, and had abnormal RV and LV MPI,
      reflecting increased preload, preserved left systolic performance, but diastolic
      dysfunction. Donor twins had diminished ejection forces and CCO in comparison
      with normal controls and recipient partners, reflecting hypovolemia. CONCLUSIONS:
      In both CCAM and recipient twins of the TTTS, diastolic dysfunction plays a
      significant role in the pathophysiology of each disorder and precedes changes in
      systolic performance. Measures of ventricular performance can help elucidate
      poorly understood mechanisms of cardiovascular compromise in the developing
      fetus.

PMID- 17533621
TI  - Can the different heat shock response thresholds found in fermenting and
      respiring yeast cells be attributed to their differential redox states?
AB  - In this study we used a heat-shock (HS) reporter gene to demonstrate that
      respiring cells are intrinsically less sensitive (by 5 degrees C) than their
      fermenting counterparts to a sublethal heat shock. We also used an oxidant
      sensitive fluorescent probe to demonstrate that this correlates with lower levels
      of sublethal reactive oxygen species (ROS) accumulation in heat-stressed
      respiring cells. Moreover, this relationship between HS induction of the reporter
      gene and ROS accumulation extends to respiring cells that have had their ROS
      levels modified by treatment with the anti-oxidant ascorbic acid and the pro
      oxidant H(2)O(2). Thus, by demonstrating that the ROS/HSR correlation previously
      demonstrated in fermenting cells also holds for respiring cells (despite their
      greater HS insensitivity and higher level of intrinsic thermotolerance), we
      provide evidence that the intracellular redox state may influence both the
      sensitivity of the heat-shock response (HSR) and stress tolerance in the yeast
      Saccharomyces cerevisiae.

PMID- 17533620
TI  - Direct in vivo access to potential gene targets of the RPD3 histone deactylase
      using fitness-based interferential genetics.
AB  - Using the fitness-based interferential genetics (FIG) approach in yeast,
      potential in vivo gene targets of the Rpd3 histone deacetylase were selected. In
      agreement with previous studies using different methods, three genes were found
      to be involved in the translational machinery (MRPL27, FHL1 and RDN1). Moreover,
      other selected genes are linked to cell-cycle control (CSE4, AMN1, VAC17 and
      GRR1). In addition to playing a crucial role in cell cycle progression to the S
      phase and participating in the G(2)-M transition, GRR1 has important functions
      related to nutrient import to the cell via the the derepression of hexose
      transporters and the induction of amino acid permeases. Consistent with this, FIG
      selection also retrieved: the PMA1 gene, encoding the plasma H(+)-membrane
      ATPase; FOL2 and FOL3, involved in folic acid biosynthesis; and UBR2, which
      indirectly downregulates the proteasome genes. Finally, the other selected genes,
      ISU1, involved in the biosynthesis of the iron-sulphur cluster in mitochondria,
      and the less well functionally defined BSC5 and YBR270c, may participate in the
      cell's antioxidant and stress defence. The genes emerging from this FIG selection
      thus appear to be part of the downstream molecular mechanisms of the TOR
      signalling pathway, accounting for its effects on cell proliferation and
      longevity. From our results on gene expression under conditions of RPD3
      overexpression, and by comparison with the available pharmacogenomics studies, it
      is proposed that FIG could be an invaluable approach for contributing to our
      understanding of complex cell regulatory systems.

PMID- 17533618
TI  - Gene expression and internalization following vector adsorption to immobilized
      proteins: dependence on protein identity and density.
AB  - BACKGROUND: Gene delivery by non-specific adsorption of non-viral vectors to
      protein-coated surfaces can reduce the amount of DNA required, and also increase
      transgene expression and the number of cells expressing the transgene. The
      protein on the surface mediates cell adhesion and vector immobilization, and
      functions to colocalize the two to enhance gene delivery. This report
      investigates the mechanism and specificity by which the protein coating enhances
      gene transfer, and determines if the protein coating targets the vector for
      internalization by a specific pathway. METHODS: Proteins (FBS, BSA, fibronectin,
      collagen I, and laminin) were dried onto culture dishes, followed by PEI/DNA
      complex adsorption for surface delivery. Reporter genes were employed to
      characterize transfection as a function of the protein identity and density.
      Vector immobilization was measured using radiolabeled plasmid, and
      internalization was quantified in the presence and absence of the endocytosis
      inhibitors chlorpromazine and genistein. RESULTS: Fibronectin coating yielded the
      greatest expression for PEI/DNA polyplexes, with maximal expression at
      intermediate protein densities. Expression in control studies with bolus delivery
      was independent of the protein identity. Substrate binding was independent of the
      protein identity; however, internalization was greatest on surfaces coated with
      fibronectin and collagen I. Inhibition of caveolae-mediated endocytosis reduced
      gene expression more than clathrin-mediated endocytosis. Similarly, inhibition of
      caveolae-mediated endocytosis significantly reduced the intracellular levels of
      DNA. CONCLUSIONS: Fibronectin at intermediate densities mediated the highest
      levels of transgene expression, potentially by targeting internalization through
      caveolae-mediated endocytosis. Substrate modifications, such as the identity and
      density of proteins, provide an opportunity for modification of biomaterials for
      enhancing gene expression.

PMID- 17533622
TI  - Estimating the cost-effectiveness of an intervention in a clinical trial when
      partial cost information is available: a Bayesian approach.
AB  - There is an increasing need to establish whether health-care interventions are
      cost effective as well as clinically effective. It is becoming increasingly
      common for cost studies to be incorporated into clinical trials, either on all
      patients or more usually on a subset of patients. Establishing the total cost per
      patient is complex, as it requires information on resource use, which may come
      from a variety of different sources. This complexity may lead to considerable
      missing data, and can result in some patients only having partial cost
      information. In this paper we consider a clinical trial consisting of 351
      patients with advanced non-small cell lung cancer comparing chemotherapy with
      standard palliative care. A subset of 115 patients was selected for the cost sub
      study. Total cost was split into four components, for which resource use was
      collected. Complete resource data were available on 82 patients. For the
      remaining patients at least one of the cost components was missing. The objective
      of this paper is to develop a Bayesian approach which simultaneously models both
      the clinical effectiveness data and the cost data, by modelling the individual
      components. This also provides estimates of the cost-effectiveness in terms of
      the Incremental Net Monetary Benefit (INMB) and Cost-Effectiveness Acceptability
      Curves (CEAC). We compare a number of different models of increasing complexity.
      The models estimate the interrelationships between the four cost components and
      survival, and thus enable a predictive distribution for each missing cost item to
      be obtained.

PMID- 17533625
TI  - Could ovarian choriocarcinoma be detected by maternal serum screening for Down
      syndrome?
AB  - The incidence of ovarian malignancies during gestation ranges from 1 in 8000 to 1
      in 20,000 deliveries. Ovarian malignancies that produce human chorionic
      gonadotropin (hCG) are limited to germ cell tumors, of which dysgerminoma is the
      most frequent (45%) malignant type encountered in pregnant patients, the others
      being ovarian choriocarcinoma and mixed germ cell tumors (Boulay and Podczaski,
      1998). In women of childbearing age, it is hard to distinguish between metastatic
      choriocarcinoma on a complete mole and primary ovarian choriocarcinoma. Treatment
      is based on adnexectomy followed by chemotherapy. Given the extreme rarity of
      these tumors, the long-term prognosis is difficult to establish. Had the
      diagnosis for our patient been made during pregnancy, the therapeutic approach
      would have been discussed in terms of gestational age. In the last trimester, we
      could have suggested cesarean section followed by adnexectomy, and then
      chemotherapy. In the second-trimester, chemotherapy could have been discussed,
      although the fetal toxicity of cisplatin chemotherapy is not firmly defined
      (Ferrandina et al., 2005). This treatment is an alternative to termination of
      pregnancy. We retrospectively studied maternal serum biochemistry so as to assess
      the possibility of a diagnosis of ovarian choriocarcinoma at the time of maternal
      serum screening for Down syndrome.

PMID- 17533626
TI  - A clinical algorithm of prenatal diagnosis of Radial Ray Defects with two and
      three dimensional ultrasound.
AB  - OBJECTIVE: To review the antenatal diagnosis of Radial Ray Defects (RRD) in a
      tertiary referral fetal medicine unit & to set out a clinical algorithm to aid
      assessment and management. METHODS: All cases of RRD isolated or associated with
      other anomalies notified to NorCAS between 2000 and 2005 were identified. Outcome
      information was obtained from paediatric records and histopathology and
      cytogenetics in cases of pregnancy interruption. RESULTS: Thirty five cases were
      referred, 17 cases were excluded including skeletal dysplasia (16). An antenatal
      diagnosis was made in 61% (11/18) - isolated limb reduction defects, Trisomy 18,
      TAR, fetal valproate syndrome, Roberts syndrome. Of the rest, 3 had a
      cordocentesis with normal chromosome fragility tests (VACTERL association,
      Goldenhar syndrome and Acrofacial dysostosis) and 4 declined testing (2 TOP with
      Cornelia de Lange, 2 ongoing pregnancies diagnosed postpartum with Fanconi
      anaemia and VACTERL association). CONCLUSIONS: The challenge of radial ray
      anomalies is to combine clinical and ultrasound expertise with input from
      clinical genetics, ultrasound and molecular testing. Our clinical algorithm
      encourages targeted sonography including 3D views for subtle face, ear and hand
      anomalies, providing a useful tool to diagnose the underlying condition, crucial
      for appropriate obstetric management and prognosticating for future pregnancies.

PMID- 17533627
TI  - Medicinal plants used by the people of Northeast India for curing malaria.
AB  - The present study showed that the people of the Northeastern region of India use
      at least 65 plants belonging to 38 families to treat malaria. Different plant
      parts such as the leaf, root, bark and fruit and in some cases the whole plant
      were used for making the herbal preparations. All crude preparations were made
      using water as the medium. The preparations were orally administered either as a
      plant crude extract, juice and decoction or leaf infusion. Of the 65 plants, 21
      were found to be used in the form of a decoction. The hard parts of the herbs
      such as the root and bark were taken in the form of a decoction. In some cases
      the ingredients of the herbal preparation also included honey or sugar. The
      present investigation also indicated that most of the preparations made for
      curing malaria were derived from single plant sources.

PMID- 17533628
TI  - The evidence based wound healing activity of Lawsonia inermis Linn.
AB  - The ethanol extract of Lawsonia inermis (200 mg/kg/day) was used to evaluate the
      wound healing activity on rats using excision, incision and dead space wound
      models. The animals were divided into three groups of six each in the excision
      model and two groups of six each in the incision model and dead space models. The
      topical application was made in the case of excision wound model, whereas, oral
      treatment was done with incision and dead space wound models. The following
      differences were noted in the group of experimental animals which were treated
      with an extract of L. inermis when compared with the control and reference
      standard animals: a high rate of wound contraction (p < 0.001), a decrease in the
      period of epithelialization (p < 0.001), high skin breaking strength (p < 0.001),
      a significant increase in the granulation tissue weight (p < 0.001) and
      hydroxyproline content (p < 0.05). The extract-treated animals showed 71%
      reduction in the wound area when compared with controls which was 58%.
      Histological studies of the tissue obtained on day 10 from the extract-treated
      group showed increased well organized bands of collagen, more fibroblasts and few
      inflammatory cells when compared with the controls which showed inflammatory
      cells, scanty collagen fibres and fibroblasts. Enhanced wound contraction,
      increased skin breaking strength, hydroxyproline and histological findings
      suggest the use of L. inermis in the management of wound healing.

PMID- 17533629
TI  - Antiinflammatory effect of the Indian Ayurvedic herbal formulation Triphala on
      adjuvant-induced arthritis in mice.
AB  - In the present study, attempts have been made to evaluate the antiarthritic
      effect of the Indian Ayurvedic herbal formulation Triphala on adjuvant-induced
      arthritis in mice and to compare it with that of the non-steroidal
      antiinflammatory drug indomethacin. Arthritis was induced by intradermal
      injection of complete Freund's adjuvant (0.1 mL) into the right hind paw of Swiss
      albino mice. Triphala (1 g/kg/bxwt) and indomethacin (3 mg/kg/bxwt) were
      administered orally for 8 days (from day 11 to 18) after adjuvant injection. The
      levels of lysosomal enzymes, tissue marker enzymes, glycoproteins and paw
      thickness were increased in adjuvant-induced arthritic animals. The body weight
      was found to be reduced when compared with the control animals. These physical
      and biochemical changes observed in arthritic animals were altered significantly
      to near normal conditions after oral administration of Triphala (1 g/kg/bxwt).
      The results obtained clearly indicate the fact that the Indian Ayurvedic herbal
      formulation Triphala has promising antiinflammatory activity.

PMID- 17533630
TI  - Molecular and cytogenetic investigation of Y chromosome deletions over three
      generations facilitated by intracytoplasmic sperm injection.
AB  - BACKGROUND: The azoospermic factor (AZF) region is critical for normal
      spermatogenesis since microdeletions and partial deletions have been associated
      with infertility. We investigate the diagnostic ability of karyotyping in
      detecting clinically relevant Y chromosome deletions. The clinical significance
      of heterochromatin deletions, microdeletions and partial AZFc deletions is also
      evaluated. METHODS: A patient with a Yq deletion, affected by severe
      oligoasthenoteratozoospermia, underwent intracytoplasmic sperm injection (ICSI)
      which resulted in the birth of a healthy baby boy. The patient, his father and
      his son underwent Y chromosome microdeletion and partial AZFc deletion screening.
      We also studied the aneuploidy rate in the sperm of the patient by fluorescent in
      situ hybridization. RESULTS: AZF microdeletions were absent in the family.
      However, microdeletion analysis confirmed that the Yq deletion was limited to the
      heterochromatin. We found a partial AZFc gr/gr deletion in all three family
      members. We observed an increased rate of sex chromosome aneuploidy in the
      infertile patient. CONCLUSIONS: Cytogenetic analysis was misleading in
      identifying the Yq breakpoint. Infertility observed in the patient was associated
      with the gr/gr partial deletion. However, because of the incomplete penetrance of
      gr/gr deletions, the consequence of the vertical transmission of the deletion
      through ICSI remains unknown.

PMID- 17533631
TI  - A prospective study on parental coping 4 months after termination of pregnancy
      for fetal anomalies.
AB  - OBJECTIVE: To identify short-term factors influencing psychological outcome of
      termination of pregnancy for fetal anomaly, in order to define those patients
      most vulnerable to psychopathology. STUDY DESIGN: A prospective cohort of 217
      women and 169 men completed standardized questionnaires 4 months after
      termination. Psychological adjustment was measured by the Inventory of
      Complicated Grief (ICG), the Impact of Event Scale (IES), the Edinburgh Postnatal
      Depression Scale (EPDS), and the Symptom Checklist-90 (SCL-90). RESULTS: Women
      and men showed high levels of posttraumatic stress (PTS) symptoms (44 and 22%,
      respectively) and symptoms of depression (28 and 16%, respectively). Determinants
      of adverse psychological outcome were the following: high level of doubt in the
      decision period, inadequate partner support, low self-efficacy, lower parental
      age, being religious, and advanced gestational age. Whether the condition was
      Down syndrome or another disability was irrelevant to the outcome. Termination
      did not have an important effect on future reproductive intentions. Only 2% of
      women and less than 1% of men regretted the decision to terminate. CONCLUSION:
      Termination of pregnancy (TOP) for fetal anomaly affects parents deeply. Four
      months after termination a considerable part still suffers from posttraumatic
      stress symptoms and depressive feelings. Patients who are at high risk could
      benefit from intensified support.

PMID- 17533632
TI  - Prenatal diagnosis of Fabry disease.

PMID- 17533633
TI  - Prenatal evaluation of facial clefts by three-dimensional extended imaging.
AB  - OBJECTIVES: To determine the prenatal diagnostic accuracy of two-dimensional
      ultrasound (2DUS) alone versus 2DUS in conjunction with three-dimensional
      ultrasonography (3DUS) including orthogonal display (OGD) and three-dimensional
      extended Imaging for cleft lip and primary palate. MATERIALS AND METHOD: Fetuses
      being suspected of having a facial cleft by previous ultrasound examination or
      family history were examined sequentially with 2DUS and then 3DUS. RESULTS: Of a
      total of 30 infants, 22 had cleft lip and nine also had cleft palate at birth.
      The use of 2DUS with or without 3DUS correctly identified all cases of cleft lips
      prenatally. However, the use of 2DUS in conjunction with 3DUS correctly
      identified more cleft primary palate than 2DUS alone (88.9% vs 22.2%, P < 0.01).
      Cleft primary palate was well demonstrated in both the multi-slice view (MSV) and
      OGD modes. In one case, a cleft palate was shown in the MSV mode but not in the
      Oblique view (OBV) mode. All the unaffected fetuses were reported as no cleft
      palate with the use of MSV mode. CONCLUSIONS: Combined approach of 2DUS and 3DUS
      with both OGD and MSV modes significantly improved the prenatal detection rate
      for a cleft palate compared with 2DUS alone (88.9% vs 22.2%) without decreasing
      the specificity.

PMID- 17533634
TI  - Site-selective surface-initiated polymerization by Langmuir-Blodgett lithography.

PMID- 17533635
TI  - Signal-amplifying conjugated polymer-DNA hybrid chips.

PMID- 17533636
TI  - Stereospecific styrene enchainment at a titanium site within a helical ligand
      framework: evidence for the formation of homochiral polystyrene.

PMID- 17533637
TI  - Polymer-based elemental tags for sensitive bioassays.

PMID- 17533638
TI  - Inhibition of alpha-glucosidase and amylase by bartogenic acid isolated from
      Barringtonia racemosa Roxb. seeds.
AB  - Barringtonia racemosa presents a wide range of therapeutic applications. In the
      course of identifying bioactives from Indian medicinal plants it was observed
      that the hexane, ethanol and methanol extracts of B. racemosa seeds displayed
      potent yeast and intestinal alpha-glucosidase inhibitory activities. The methanol
      extract was found to be superior among them. However, none of the extracts
      exhibited pancreatic alpha-amylase inhibitory activity, rather the ethanol and
      methanol extracts accelerated the alpha-amylase enzyme activity. Interestingly,
      however, bartogenic acid isolated from the methanol extract inhibited alpha
      amylase also. This is the first report identifying alpha-glucosidase inhibitory
      activity in B. racemosa seed extracts and assigning to bartogenic acid an alpha
      glucosidase and amylase inhibitory property. The presence of bartogenic acid in
      B. racemosa seeds as a major compound is also reported for the first time in this
      communication.

PMID- 17533639
TI  - The medieval physician Avicenna used an herbal calcium channel blocker, Taxus
      baccata L.
AB  - Calcium channel blockers are drugs which are important for current medical
      therapy. The first examples of synthetic congeners of this class of drugs appear
      around at the beginning of the 1960s. Review of the current and historical
      literature shows that Avicenna (Ibn Sina) (980-1037) had used the herbal drug
      'Zarnab' (Taxus baccata L.) as a cardiac remedy. The leaves of T. baccata contain
      an alkaloid mixture (taxines). It was recently demonstrated that this drug
      possessed calcium channel blocking activity. So, it is evident that Avicenna used
      a drug with calcium channel blocking activity much earlier than the arrival of
      synthetic drugs belonging to the same pharmacological group.

PMID- 17533640
TI  - Mites for the control of pests in protected cultivation.
AB  - The production of crops under protected conditions is increasing worldwide. Owing
      to growing consumer demands for healthy and green produce, and intensifying
      pesticide resistance, non-chemical solutions--foremost among which is biological
      control--are being sought. The authors review recent advances related to the
      application of predatory mites for the control of greenhouse pests, and discuss
      interactions among acarine biocontrol agents (ABAs) and the effects of crop
      plants and new technologies on ABAs, such as artificial lighting, elevated carbon
      dioxide levels and genetically modified organisms. This is followed by a
      discussion of the problems associated with the search for and use of new ABAs,
      including management, the benefits of modelling and avenues of future research.

PMID- 17533642
TI  - Proteomics of European beech (Fagus sylvatica L.) seed dormancy breaking:
      influence of abscisic and gibberellic acids.
AB  - A proteomic approach was used to analyze mechanisms of dormancy breaking in beech
      (Fagus sylvatica L.) seeds and the participation of abscisic and gibberellic
      acids (ABA and GA) in this process. After imbibition in water, ABA, or GA3
      solutions, beechnuts were subjected to cold stratification, which breaks their
      dormancy. ABA delayed, whereas GA3 promoted seed dormancy breaking. Proteome maps
      for water, ABA, and GA3 were established, which displayed 1544 silver-stained
      spots. A total of 74 spots, showing significant changes in volume, were
      identified by MS. Of these, 18, 45, and 16 spots were identified as water-, ABA-,
      and GA3-responsive, respectively (five were regulated by both hormones). The
      classification of proteins showed that most of the proteins associated with
      dormancy breaking in water are involved in energy metabolism and protein
      destination. Most of the ABA-responsive proteins are involved in protein
      destination, energy metabolism, and development. Most of the GA3-responsive
      proteins are involved in energy metabolism (many more than for ABA and water) and
      plant defense. We conclude that the mechanism of seed dormancy breaking involves
      the proteins of many processes, beginning with hormone signal initiation, through
      signal transduction, transcription, protein synthesis, energy metabolism, storage
      materials, and ending with the cell cycle.

PMID- 17533641
TI  - Direct analysis of the extracellular proteome from two strains of Helicobacter
      pylori.
AB  - Helicobacter pylori extracellular proteins are of interest because of possible
      roles in pathogenesis, host recognition, and vaccine development. We utilized a
      unique approach by growing two strains (including one nonsequenced strain) in a
      defined serum-free medium and directly analyzing the proteins present in the
      culture supernatants by LC-MS/MS. Over 125 proteins were identified in the
      extracellular proteomes of two H. pylori strains. Forty-five of these proteins
      were enriched in the extracellular fraction when compared to soluble cell
      associated protein samples. Our analysis confirmed and expanded on the previously
      reported H. pylori extracellular proteome. Extracellular proteins of interest
      identified here included cag pathogenicity island protein Cag24 (CagD); proteases
      HP0657 and HP1012; a polysaccharide deacetylase, HP0310, possibly involved in the
      hydrolysis of acetyl groups from host N-acetylglucosamine residues or from
      residues on the cell surface; and HP0953, an uncharacterized protein that appears
      to be restricted to Helicobacter species that colonize the gastric mucosa. In
      addition, our analysis found eight previously unidentified outer membrane
      proteins and two lipoproteins that could be important cell surface proteins.

PMID- 17533643
TI  - Immunodominant Francisella tularensis antigens identified using proteome
      microarray.
AB  - Stimulation of protective immune responses against intracellular pathogens is
      difficult to achieve using non-replicating vaccines. BALB/c mice immunized by
      intramuscular injection with killed Francisella tularensis (live vaccine strain)
      adjuvanted with preformed immune stimulating complexes admixed with CpG, were
      protected when systemically challenged with a highly virulent strain of F.
      tularensis (Schu S4). Serum from immunized mice was used to probe a whole
      proteome microarray in order to identify immunodominant antigens. Eleven out of
      the top 12 immunodominant antigens have been previously described as
      immunoreactive in F. tularensis. However, 31 previously unreported immunoreactive
      antigens were revealed using this approach. Twenty four (50%) of the ORFs on the
      immunodominant hit list belonged to the category of surface or membrane
      associated proteins compared to only 22% of the entire proteome. There were eight
      hypothetical protein hits and eight hits from proteins associated with different
      aspects of metabolism. The chip also allowed us to readily determine the IgG
      subclass bias, towards individual or multiple antigens, in protected and
      unprotected animals. These data give insight into the protective immune response
      and have potentially important implications for the rational design of non-living
      vaccines for tularemia and other intracellular pathogens.

PMID- 17533644
TI  - Proteomic analysis of the cambial region in juvenile Eucalyptus grandis at three
      ages.
AB  - Recent advances in genomics and proteomics have provided an excellent opportunity
      to understand complex biological processes such as wood formation at the gene and
      protein levels. The aim of this work was to describe the proteins participating
      in the processes involved in juvenile wood formation by isolating proteins from
      the cambial region of Eucalyptus grandis, at three ages of growth (6-month-old
      seedlings, 3- and 6-year-old trees), and also to identify proteins differentially
      expressed. Using a 2-D-LC-MS/MS strategy we identified a total of 240 proteins,
      with 54 corresponding spots being present in at least two ages. Overall, nine
      proteins classified into the functional categories of metabolism, cellular
      processes, and macromolecular metabolism showed significant changes in
      expression. Proteins were classified into seven main functional categories, with
      metabolism representing 35.2% of the total proteins identified. The comparison of
      the reference maps showed not only differences in the expression pattern of
      individual proteins at each age, but also among isoforms. The results described
      in this paper provide a dynamic view of the proteins involved in the formation of
      juvenile wood in E. grandis.

PMID- 17533645
TI  - Proteome and cytoskeleton responses in osteosarcoma cells with reduced OXPHOS
      activity.
AB  - We have recently shown disorganization of the vimentin network in cultured cells
      deficient in oxidative phosphorylation (OXPHOS). We describe here the cellular
      responses to OXPHOS deficiency in osteosarcoma cells upon complex I (CI) and
      complex IV (CIV) inhibition, and upon the lack of mitochondrial DNA (rho0 cells).
      We examined the cytoskeletal organization and the distribution of mitochondria
      and analysed total proteome by 2-DE and vimentin expression by ELISA. Upon CIV
      inhibition and in rho0 cells, the vimentin network had collapsed around the
      nucleus and formed thick bundles. The mitochondria formed a perinuclear crescent
      upon CIV inhibition, whereas they accumulated around the nucleus in the rho0
      cells, where the amount of vimentin was increased. Analysis of the total proteome
      revealed that a lack of mitochondrial DNA or inhibition of CI or CIV led to
      changes in the expression of cytoskeletal and cytoskeleton-associated proteins
      and proteins involved in apoptosis, OXPHOS, glycolysis, the tricarboxylic acid
      cycle, and oxidative stress responses. Our findings suggest that a deficiency in
      the energy converting system and oxidative stress can lead to cytoskeletal
      changes.

PMID- 17533646
TI  - Re sodium cromoglicate: an ineffective drug or meta-analysis misused?

PMID- 17533647
TI  - Sodium cromoglicate: an ineffective drug or meta-analysis misused?
AB  - Sodium cromoglicate (SCG) has been available since around 1970 for the treatment
      of asthma and other allergic disorders in both adults and children. It has been
      approved for use around the world. Over the period of its development, a number
      of different formulations were introduced. In 1999, a systematic review of SCG
      use in childhood asthma was carried out and reported initially as a poster.
      Further systematic reviews and papers followed from the same authors and finally
      a Cochrane Collaboration review was published in 2003. All concluded that SCG was
      ineffective in paediatric asthma. Both the British Thoracic Society Guidelines
      for the treatment of paediatric asthma and the Model List of Essential Drugs of
      the WHO now reflect these conclusions. This paper looks carefully at the
      conclusions of these systematic reviews and raises concerns about the
      interpretation of the results. These failed to take adequate account of the
      changes with time in both the formulations used and the age groups examined, and
      also failed to take adequate note of the totality of information available over
      all end-points. One primary end-point was based on only four out of the 24
      studies included in the review. Rather than having no effect, it is demonstrated
      that a considerable body of evidence favours SCG compared to placebo and, far
      from being ineffective, the drug appears to be effective particularly in older
      children. This article replaces a previously published version. DOI:
      10.1002/pst.258.

PMID- 17533648
TI  - Comment on sodium cromoglicate: an ineffective drug or meta-analysis misused? by
      Stevens et al., Pharmaceutical Statistics.

PMID- 17533649
TI  - Insecticide resistance in disease vectors of public health importance.
AB  - Vector-borne diseases are a global problem--a trend that may only increase if
      global temperature rises and demographic trends continue--and their economic and
      social impact are enormous. Insecticides play a vital role in the fight against
      these diseases by controlling the vectors themselves in order to improve public
      health; however, resistance to commonly used insecticides is on the rise. This
      perspective outlines the major classes of disease vector control agents and the
      mechanisms of resistance that have evolved, arguing that effective resistance
      management strategies must carefully monitor resistance in field populations and
      use combinations of the limited modes of action available to best effect.
      Moreover, the development of novel insecticide classes for control of adult
      mosquitoes and other vectors becomes increasingly important.

PMID- 17533650
TI  - Berry fruits.

PMID- 17533651
TI  - Cranberry and blueberry: evidence for protective effects against cancer and
      vascular diseases.
AB  - Growing evidence from tissue culture, animal, and clinical models suggests that
      the flavonoid-rich fruits of the North American cranberry and blueberry
      (Vaccinium spp.) have the potential ability to limit the development and severity
      of certain cancers and vascular diseases including atherosclerosis, ischemic
      stroke, and neurodegenerative diseases of aging. The fruits contain a variety of
      phytochemicals that could contribute to these protective effects, including
      flavonoids such as anthocyanins, flavonols, and proanthocyanidins; substituted
      cinnamic acids and stilbenes; and triterpenoids such as ursolic acid and its
      esters. Cranberry and blueberry constituents are likely to act by mechanisms that
      counteract oxidative stress, decrease inflammation, and modulate macromolecular
      interactions and expression of genes associated with disease processes. The
      evidence suggests a potential role for dietary cranberry and blueberry in the
      prevention of cancer and vascular diseases, justifying further research to
      determine how the bioavailability and metabolism of berry phytonutrients
      influence their activity in vivo.

PMID- 17533653
TI  - The bioavailability and absorption of anthocyanins: towards a better
      understanding.
AB  - Evidence that anthocyanin compounds have beneficial effects for health are
      increasingly being reported in the scientific literature and these compounds are
      now widely recognised as potential therapeutic compounds. Berry fruit are rich
      sources of anthocyanins and berry fruit products or derived beverages can provide
      10s to 100s of milligrams of anthocyanins in a single serve. Anthocyanins exhibit
      complex chemical behaviours in vitro and this will result in complex behaviour in
      vivo. This review attempts to summarize some aspects of anthocyanin biochemistry
      and discusses these in the context of what is currently known about
      bioavailability and absorption. Compared with other flavonoid groups, such as
      flavonols, relatively little is known about details and mechanisms of anthocyanin
      absorption and transport and much remains to be discovered.

PMID- 17533652
TI  - Berry anthocyanins as novel antioxidants in human health and disease prevention.
AB  - Edible berries, a potential source of natural anthocyanin antioxidants, have
      demonstrated a broad spectrum of biomedical functions. These include
      cardiovascular disorders, advancing age-induced oxidative stress, inflammatory
      responses, and diverse degenerative diseases. Berry anthocyanins also improve
      neuronal and cognitive brain functions, ocular health as well as protect genomic
      DNA integrity. This chapter demonstrates the beneficial effects of wild
      blueberry, bilberry, cranberry, elderberry, raspberry seeds, and strawberry in
      human health and disease prevention. Furthermore, this chapter will discuss the
      pharmacological benefits of a novel combination of selected berry extracts known
      as OptiBerry, a combination of wild blueberry, wild bilberry, cranberry,
      elderberry, raspberry seeds, and strawberry, and its potential benefit over
      individual berries. Recent studies in our laboratories have demonstrated that
      OptiBerry exhibits high antioxidant efficacy as shown by its high oxygen radical
      absorbance capacity (ORAC) values, novel antiangiogenic and antiatherosclerotic
      activities, and potential cytotoxicity towards Helicobacter pylori, a noxious
      pathogen responsible for various gastrointestinal disorders including duodenal
      ulcer and gastric cancer, as compared to individual berry extracts. OptiBerry
      also significantly inhibited basal MCP-1 and inducible NF-kappabeta
      transcriptions as well as the inflammatory biomarker IL-8, and significantly
      reduced the ability to form hemangioma and markedly decreased EOMA cell-induced
      tumor growth in an in vivo model. Overall, berry anthocyanins trigger genetic
      signaling in promoting human health and disease prevention.

PMID- 17533654
TI  - The bioavailability of raspberry anthocyanins and ellagitannins in rats.
AB  - The fate of anthocyanins and ellagitannins in rats was monitored following
      ingestion of raspberry juice. After 1 h low nM concentrations of unmetabolised
      anthocyanins were present in plasma but these declined by 2 h and after 4 h they
      were no longer detectable. For the first 2 h there was an almost full recovery of
      anthocyanins as they passed from the stomach through the duodenum/jejunum and
      into the ileum. After 3 h less than 50% were recovered, and the levels declined
      rapidly thereafter. Excretion of raspberry anthocyanins in urine over a 24 h
      period was equivalent to 1.2% of the amount ingested. Trace quantities of
      anthocyanins were detected in the caecum, colon and faeces and they were absent
      in extracts of liver, kidneys and brain. Urine also contained a number of
      phenolic acids but most were present in quantities well in excess of the 918 nmol
      of anthocyanins present in the ingested juice. These findings indicate that
      raspberry anthocyanins per se are poorly absorbed, probably prior to reaching the
      ileum, and that substantial amounts pass from the small to the large intestine
      where they are degraded by colonic bacteria. Ellagitannins disappeared in the
      stomach without accumulation of ellagic acid.

PMID- 17533655
TI  - Insecticide susceptibility of surviving Cotesia plutellae (Hym: Braconidae) and
      Diaeretiella rapae (M'Intosh) (Hym: Aphidiidae) as affected by sublethal
      insecticide dosages on host insects.
AB  - The effects of sublethal dosages of insecticides applied to Plutella xylostella
      L. (Lepidoptera: Yponomeutidae) and Lipaphis erysimi Kaltenbach (Homoptera:
      Aphidiidae) on the insecticide susceptibility of the surviving endoparasitoids,
      Cotesia plutellae Kurdjumov (Hymenoptera: Braconidae) and Diaeretiella rapae
      (M'Intosh) (Hymenoptera: Aphidiidae), were studied in Shangjie, Minhou, China.
      The susceptibility to methamidophos and the sensitivity of acetylcholinesterase
      (AChE) to methamidophos and dichlorvos in the adults of host insects were
      substantially lower than those in the two parasitoids. The host insects were
      treated with sublethal dosages of methamidophos in P. xylostella and of
      methamidophos and avermectin in L. erysimi. The cocoon formation in the two
      parasitoids decreased significantly, from 35.0% (control) to 13.0% (with
      methamidophos treatment) for C. plutellae; from 20.6% (control) to 9.0% (with
      methamidophos treatment) and from 24.3% (control) to 16.7% (with avermectin
      treatment) for D. rapae. The susceptibility to methamidophos of the resultant
      emerging adults of the two parasitoids was found to be significantly lower than
      that of the control when the parasitoids were left in contact with the same
      dosages of methamidophos. The average AChE activity inhibition by methamidophos
      and dichlorvos in 34-60 adults of the two parasitoids that emerged from the
      treatments (15.1% and 31.8% respectively for C. plutellae, and 21.1% and 26.9%
      for D. rapae) was also significantly lower than those of the controls (55.4% and
      48.3% respectively for C. plutellae, and 42.9% and 51.7% for D. rapae). The
      bimolecular rate constant (k(i)) values of AChE to methamidophos and dichlorvos
      in the adults of parasitoids without the insecticide treatment were 1.78 and 1.56
      times as high as those that emerged from the host insects treated with
      methamidophos for C. plutellae, and 1.91 and 1.66 times as high as those in the
      case of D. rapae. It is suggested that there is a difference in AChE sensitivity
      to insecticides between the resultant emerging parasitoids with and without
      insecticide pretreatment. Furthermore, the introduction of the insecticides to
      the host insects could be an important factor in the insecticide resistance
      development of the endoparasitoids. The natural selectivity would favour the
      parasitoids that had developed an insensitivity to the insecticide(s).

PMID- 17533656
TI  - A comparative evaluation of Origanum onites essential oil and its four major
      components as larvicides against the pine processionary moth, Thaumetopoea
      wilkinsoni Tams.
AB  - The pine processionary moth (PPM), Thaumetopoea wilkinsoni Tams. (Lepidoptera:
      Thaumatopoeidae), is an important forest pest in the Mediterranean area, and
      urticating hairs of the caterpillars of this species cause allergic reactions on
      skin of humans and animals. In the present study, the larvicidal activities of
      Turkish oregano (Origanum onites L.) essential oil and its four major components,
      carvacrol, gamma-terpinene, terpinen-4-ol and thymol, were evaluated against
      fourth/fifth-instar larvae of PPM under laboratory conditions. The essential oil
      was larvicidal to PPM with an LD(50) value of 3800 microL L(-1) when 0.1 mL was
      applied per larva. Carvacrol was the most toxic component found in the essential
      oil (LD(50) = 3100 microL L(-1)), followed by thymol (LD(50) = 5500 microL L(
      1)). The other two components, gamma-terpinene and terpinen-4-ol, were less
      effective. The results showed that Turkish oregano essential oil and its two
      components, carvacrol and thymol, could be potential alternatives to synthetic
      insecticides for the control of PPM.

PMID- 17533657
TI  - Establishing rights over the Arctic Ocean.

PMID- 17533658
TI  - Accidental death from acute selenium poisoning.

PMID- 17533659
TI  - Accidental death from acute selenium poisoning.

PMID- 17533661
TI  - Re: Gallstone ileus.

PMID- 17533662
TI  - Perspectives of a rural doctor's spouse.

PMID- 17533664
TI  - Intravenous rehydration of children with gastroenteritis: which solution is
      better? Authors' response.

PMID- 17533663
TI  - Severe air embolism resulting from a perforated cap on a high-flow three-way
      stopcock connected to a central venous catheter.

PMID- 17533666
TI  - Expect rise in suture prices until increase in market pressure.

PMID- 17533665
TI  - Snapshot of hospital quality reporting and pay-for-performance under Medicare.
AB  - This paper examines the impact that Medicare pay-for-performance (P4P) might have
      upon hospital payment. It uses the initial two quarters of a national quality
      database to model financial gains or losses using the Premier Hospital Quality
      Incentive Demonstration rules, as well as the P4P approach recommended by the
      Medicare Payment Advisory Commission (MedPAC). Findings reveal variation among
      all types of hospitals and across all measures within each of the three
      conditions studied: heart attack, heart failure, and pneumonia. Initially,
      hospitals' financial gains and losses likely will be marginal using the Premier
      demonstration payment rules and somewhat larger under the MedPAC recommendations
      as modeled.

PMID- 17533667
TI  - HIV patient names to be tracked in all 50 states by year's end.

PMID- 17533668
TI  - Interferon-like virus-inhibitor induced in human leukocytes by
      phytohemagglutinin.
AB  - Phytohemagglutinin, an extract of the kidney bean, Phaseolus vulgaris, induces in
      human leukocyte cultures an inhibitor of the cytopathic effects of Sindbis virus.
      The physicochemical and biological properties of this virus-inhibitor are similar
      to those of interferon induced by Newcastle disease virus, except for an
      instability at pH 2 and 10 and at 56 degrees C.

PMID- 17533669
TI  - Cytochemical studies concerning the occurrence and distribution of RNA in
      plastids of Zea mays.
AB  - The occurrence of RNA in plastids from etiolated and green maize leaves was
      demonstrated cytochemically, with both the light and the electron microscope.
      Etiolated leaves were allowed to incorporate tritiated cytidine for several hours
      and were subsequently fixed in formalin. Radioautographs of leaf sections 2 micro
      thick showed silver grains over the regions of the cytoplasm containing plastids.
      Plastids in these sections appeared intensely basophilic when stained with azure
      B. Both the basophilia and radioactivity were removable with ribonuclease,
      clearly demonstrating the occurrence of RNA in these organelles. Examination
      under the electron microscope of similar plastids which had been fixed in
      formalin revealed a particulate component in the plastid measuring approximately
      170 A in diameter. This particulate component was completely removable with
      ribonuclease. Thus,it was concluded that RNA occurs in a particulate form in
      plastids from etiolated leaves. Mature plastids, when stained with azure B, did
      not appear basophilic under the light microscope. Nevertheless, when formalin
      fixed tissues were examined with the electron microscope, the mature plastids
      were seen to contain particles in the stroma, identical in appearance with those
      visible in the plastids in etiolated leaves. Osmium tetroxide-fixed tissues were
      also examined with the electron microscope. Particles similar to those seen in
      plastids fixed with formalin were observed, although the results obtained with
      this fixative were variable. It is concluded that plastids from etiolated and
      green maize leaves contain RNA in a particulate form which resembles ribosomes.

PMID- 17533670
TI  - Studies on Japanese B encephalitis virus. III. Propagation and assay of Japanese
      B encephalitis virus in a stable line of porcine kidney cells.

PMID- 17533671
TI  - Autoradiographic study of cell migration during histogenesis of cerebral cortex
      in the mouse.

PMID- 17533672
TI  - Left atrial and left ventricular pressures in subjects without cardiovascular
      disease: observations in eighteen patients studied by transseptal left heart
      catheterization.
AB  - Transseptal left heart catheterizations were carried out in 18 patients without
      apparent evidence of organic cardiovascular disease. These studies have permitted
      delineation of the pressures that exist in the left side of the heart in normal
      subjects studied in a basal physiologic state.

PMID- 17533673
TI  - The vascular contribution to osteogenesis. III. Changes in the growth cartilage
      caused by experimentally induced ischaemia.

PMID- 17533675
TI  - Abstracts of the 21st Congress of the German-speaking Society of Intraocular Lens
      Implantation and Refractive Surgery, 16-17 March 2007, Potsdam, Germany.

PMID- 17533676
TI  - Recommended practices for managing the patient receiving local anesthesia.

PMID- 17533674
TI  - Abstracts of the 12th Annual Interventional Vascular Therapeutics Angioplasty
      Summit-Transcatheter Cardiovascular Therapeutics Asia Pacific Symposium, April 25
      27, 2007, Seoul, Korea.

PMID- 17533677
TI  - Recommended practices for the prevention of unplanned perioperative hypothermia.

PMID- 17533678
TI  - Recommended practices for reducing radiological exposure in the perioperative
      practice setting.

PMID- 17533679
TI  - Belgium Royal Academy of Medicine membership list.

PMID- 17533681
TI  - Investing in Mental Health Policy and Economics Research. Abstracts of the 8th
      Workshop on Costs and Assessment in Psychiatry, March 9-11, 2007, Venice, Italy.

PMID- 17533680
TI  - Abstracts of the 2nd International Congress on Prediabetes and the Metabolic
      Syndrome, Barcelona, Spain, April 25-28, 2007.

PMID- 17533682
TI  - [Abstracts of the 4th Francophone Conference on HIV/AIDS, Paris, France, 29-31
      March 2007].

PMID- 17533683
TI  - [First success with a subretinal implant].

PMID- 17533684
TI  - [Possibilities of telemedicine].

PMID- 17533685
TI  - Abstracts of the Annual Conference of the Swiss Society for Allergology and
      Immunology and the Swiss Society of Dermatology and Venerology, Basel,
      Switzerland, April 19-20, 2007.

PMID- 17533686
TI  - Findings of research misconduct.

PMID- 17533687
TI  - Abstracts of the 54th Annual Meeting of the Japanese Association for Laboratory
      Animal Science, May 23-25, 2007, Tokyo, Japan.

PMID- 17533688
TI  - Role of ultrasound in assessment of early rheumatoid arthritis.
AB  - This report reviews imaging methods used for diagnosis and monitoring of
      rheumatoid arthritis, with emphasis on the role of ultrasonography.
      Traditionally, conventional radiography has been useful in detecting and
      monitoring the extent of joint destruction in rheumatic disease. However, it is
      particularly difficult to detect pathological joint changes in the early stages.
      Magnetic resonance imaging is able to detect inflammation of the synovial
      membrane and erosions but is limited by cost and availability. Ultrasound has
      recently emerged as a useful and potentially reliable method for assessing the
      degree of joint inflammation and erosion in patients with early rheumatoid
      arthritis.

PMID- 17533689
TI  - In memoriam Knut Schmidt-Nielsen. 24 September 1915 - 25 January 2007.

PMID- 17533690
TI  - [Pituitary insufficiency following head trauma].

PMID- 17533692
TI  - [Study on sociocultural history of therapeutic efficacy and processing of chinese
      materia medica].
AB  - The historical evolving examples of the confirmation of therapeutic efficacy of
      some Chinese materia medica, the social fashion of using medicine, and the
      processing methods of Chinese materia medica indicate that the social trend of
      thoughts, customs and economic factors in different ages affected the various
      aspects of Chinese materia medica. So, Chinese materia medica possesses very
      outstanding social and cultural features. Not all the actions of Chinese materia
      medica recorded came from the experiences of doctors. The understanding level to
      the nature in different ages decides what kind of drugs they would accept. There
      are three kinds of drug processing in ancient times: effective medicinal
      processing, fantastic Taoist processing and invalid trading processing. Based on
      the study of sociocultural history of therapeutic efficacy and processing of
      Chinese materia medica. It is crucial that the history and medical literature
      research on Chinese materia medica and pharmacy should be raised to the position
      as important as clinical and experiment researches.

PMID- 17533693
TI  - [The influence of Huang di nei jing (Huangdi's inner classic) on Shuo wen jie zi
      (the origin of Chinese characters)].
AB  - It is very likely that The Origin of Chinese Characters is influenced by Huang
      Di's Inner Classic after investigating the author of The Origin of Chinese
      Characters and identifying the publishing times of them. The following
      conclusions are reached through comparing and analyzing thinking modes,
      philosophical conception, and knowledge of human anatomy, disease and treatment
      in them: the knowledge of traditional Chinese medicine (TCM) contained in The
      Origin of Chinese Characters is in direct line of succession with the Inner
      Classic; the universe and ecomedical thinking modes of "heaven-earth-human being"
      in The Origin of Chinese Characters and the Inner Classic respectively are cut
      from the same cloth; the theories of qi, yin-yang, and the five phases, the
      theoretical foundation of the Inner Classic, can be traced back to their sources
      through The Origin of Chinese Characters; The Origin of Chinese Characters traces
      back to characters' origin and original meanings through analyzing their
      structures, therefore, the book is important for us to study and read the Inner
      Classic, and to probe into the origin of TCM as well.

PMID- 17533694
TI  - [Analysis on status of versions of Sheng ji zong nlu (complete record of holy
      benevolence) in Emperor Qianlong's reign].
AB  - OBJECTIVE: The Qianlong edition of Sheng Ji Zong Lu (Complete Record of Holy
      Benevolence), xylographed and reprinted by Wang Mingke in the fifty-second year
      of Emperor Qianlong's reign (1787) during the Qing Dynasty is incomplete and
      seriously patched up: (1) There is only 197 volumes in this version, with 3
      volumes missing from the 200-volume original version; (2) This version is
      seriously shifted, tampered, and deleted in the sections of "Sores", "wounds and
      fractures", "miscellaneous therapies", especially the "Pediatrics" section; (3)
      Some contents, supplemented to the "Pediatrics" section by later generations,
      were lost when Wang xylographed the version. The supplemented parts are identical
      with that of the "Sheng ji zong llu zuan yao (Abridged Complete Records of Holy
      Benevolence)", demonstrating that both were derived from the same source, or the
      Xiangshi'an's version. From the angle of version, the version of Emperor Qianlong
      reign is not a good one, because the versions of Sheng ji zong lu are not well
      circulated in China.

PMID- 17533695
TI  - [Addendum of investigation on versions of Ben cao pin hui jing yao].
AB  - OBJECTIVE: There is a great varieties of transcriptions of the versions of Liu
      Wentai's Bencao Pinhui Jingyao existed, including over 20 versions of domestic
      and oversea transcriptions, 21 versions of modern printing and facsimile, and 2
      remained manuscripts newly discovered.

PMID- 17533696
TI  - [Exploration on the academic achievements of YAN Cangshan's Yi jingjia ting zi
      liao ji (self-treatment for pestilent convulsion)].
AB  - OBJECTIVE: In 1929, yi jing (pestilent convulsion) was prevalent in Shanghai, Yan
      Cangshan, a noted modern physician, was active in treating and rescuing the
      patients. Yi jingjia ting zi liao ji is a book of the summary on his clinical
      experience in the treatment of yi jing (pestilent convulsion). It is the first
      monograph on epidemic diseases carrying the title of yi jing (pestilent
      convulsion). There were many creative ideas about the name of disease,
      prescriptions, and medication, etc, embodying Yan's academic thought and
      achievements. It is of great reference value up to now.

PMID- 17533697
TI  - [Review of medical healthcare of Guangxi during 1930s].
AB  - OBJECTIVE: In 1930s, Gui government adopted a series of measures to develop
      Guangxi medical healthcare, including establishment of organization, fund
      investment, training of medical personnel, and the daily hygienic facility, etc.
      It raised the local medical health level. However, by observing such target as
      the number of doctors per ten thousand population, the number of epidemics of
      diseases, the population mortality rate and causes of death, death age and so on,
      one can see the insufficiency of healthcare cause at that time. Through the
      summary of historical experiences, it is worthy of drawing lessons to today's
      cause of health, prevention and treatment of epidemics.

PMID- 17533698
TI  - [Historical changes of diagnostic methods for intestinal obstruction].
AB  - OBJECTIVE: Abstract Intestinal obstruction is one of the earliest diseases known
      by humanity with its diagnosis experiencing a long course of history, achieving
      full-grown improvement, attracting worldwide attention. However, there are also
      some issues worthy of investigation. For example, the diagnosis of strangulated
      intestinal obstruction is still a challenge; The rate of misdiagnosis is 37% 
      50%, etc. Thus, long-term efforts may be still needed to solve these problems.

PMID- 17533699
TI  - [A brief history of liver transplantation].
AB  - Since 1950s, the idea of liver transplantation (LT) was proposed, the technique
      of LT had been gradually and widely appliedin the field of clinical surgery,
      experiencing three stages of animal experiment, clinical probation and clinical
      application. It is generally acknowledged as the common and effective therapeutic
      method for terminal stage of liver diseases. Recently, the technique of LT has
      made rapid progress in Chinese mainland, Hong Kong and Taiwan. China is the
      second biggest LT country in the world, only next to USA.

PMID- 17533700
TI  - [Which is right? "Theory of channel" or "Theory of blood vessels"].
AB  - The ancient medical science of Jingmai (Channel or blood vessel) applied the
      running sensation along channels of the so-called "Mai" to diagnose and treat
      diseases. Unfortunately, this had been lost in the Han Dynasty. Related
      information is recorded in the official history; there are related evidences in
      the unearthed Mai shu (The Book of Channel) and "Mairen (The Statue of Channel)",
      including the rediscovery and modern researches on the running sensation along
      channels; the successful cases of diagnosis and treatment by the method of
      running sensation along channels. The scholars supported the theory of blood
      vessel query the above ideas, which need to assemble large numbers of researches
      of the theory of channel to resolve the problems.

PMID- 17533701
TI  - [Exploration and analysis of theories of five phases, eight trigrams and four
      elements].
AB  - The theory of five phases is significantly different from that of eight trigrams
      of I Ching (Book of Changes): the eight trigrams represent the materials or
      phenomena in the nature, whereas five phases put "metal" created by human
      activities into nature, which organically incorporate the human activities and
      all the things in the nature and promote the formation of holistic concept of
      heaven and human being. Without the attendance of man, earth can't generate
      metal, metal can't restrict wood, and metal can't generate water. So, it can be
      concluded that the five phases is the improved eight trigrams. Together with
      monism of original qi and the dualism of yin-yang, it contributes to Chinese
      medicine the scientific world view and methodology to shake off wizards, and is
      also the root cause for the Chinese medicine being good at resolving complicated
      problems. The theory of five phases is also significantly different from the
      theory of four elements in the western world: The five phases create the
      relationship of the interaction and interrelation among everything on earth and
      is the embryo and basis of systemic science. The theory of four elements belongs
      to constructivism and is the sprout of analytical science.

PMID- 17533702
TI  - [Diagnosis and management of zygomaticomaxillary complex fractures].
AB  - The zygornaticomaxillarx complex (ZMC) plays an important role in maintaining the
      structure and function of the face. The prominent convex shape of the ZMC makes
      it particularly vulnerable to trauma, resulting in a tetrapod fracture involving
      all four buttresses. ZMC fracture usually leads to local depressed deformities,
      even dysfunction such as limited mouth opening and diplopia. This article
      lescribes the etiology, clinical features, surgical approaches and postoperative
      complications of ZMC fractures based on our own clinical experiences and
      literature review. It is believed that lateral brow incision combined with
      intraoral incision can provide better access to ZMC fractures and avoid the
      disadvantages caused by coronal incision. This surgical approach leaves minimal
      scar and injury to the facial nerve, with better esthetic and functional
      outcomes. Supported by Shanghai Leading Academic Discipline Project (Grant No.
      Y0203).

PMID- 17533703
TI  - [Clinical analysis of colour distribution in tetracycline teeth].
AB  - PURPOSE: To analyze the colour range and distribution of tetracycline teeth, and
      the difference from normal teeth. METHODS: 142 cases with 468 anterior
      tetracycline teeth and 100 cases with 200 normal anterior teeth were collected.
      The color was measured by a computer-aided Shade-Eye NCC colorimeter, and
      expressed in terms of 3 coordinate values (L,a,b) of the CIE-1976-Lab color
      system. Chroma (Cab)and hue (h(ab) degrees)were calculated according to the value
      of a and b. The data were analyzed with SAS6.12 software package for description,
      Student's t test and Duncan test. RESULTS: The range of L, a, b Cab, h(ab)
      degrees of tetracycline teeth was 42.33-77.00, -0.6-9.6, 2.67-31.5, 5.24-31.89,
      38.62 degrees-95.47 degrees, respectively. Significant difference of L value and
      hue (h(ab) degrees) was found between tetracycline teeth and normal teeth (P <
      0.01), which indicated that tetracycline teeth were darker and redder than normal
      teeth. There was no difference of chroma (Cab) between tetracycline teeth and
      normal teeth (P > 0.05). Moreover there was significant difference of L value
      between canine and central incisor, and of H value (h(ab) degrees) between canine
      and lateral incisor in tetracycline teeth, which indicated that canine was darker
      and redder than incisor, and redder than lateral incisor, but there was no
      significant difference in chroma (Cab) among all anterior teeth and no difference
      in L, a, b between central incisor and lateral incisor. CONCLUSIONS: The study
      showed the color distribution of tetracycline teeth was wider and more dispersive
      than normal teeth, and much darker and redder than normal teeth. Supported by
      Shanghai Leading Academic Discipline

PMID- 17533704
TI  - [Clinical effect of pit and fissure sealant used in combination with self-etching
      adhesive on permanent teeth].
AB  - PURPOSE: To determine the role of pit and fissure sealant used in combination
      with self-etching adhesive in retention of the sealants and caries decrease of
      the permanent teeth. METHODS: Sixty two children aged 6-14 years old were chosen
      from the outpatients in the Department of Pediatric Dentistry, the first or the
      second permanent molars (n= 156) were sealed with two kinds of sealant. The tooth
      in one side was sealed with sealant (Concise, 3M-ESPE) and self-etching system
      (Adper and Prompt, 3M-ESPE) while the tooth in the other side was sealed with
      sealant (Concise, 3M-ESPE) and phosphate acid system. All the patients were
      followed up and reexamined 3, 6 and 12 months after treatment. Statistical
      analysis was carried out with SPSS 12.0 (SPSS Inc., Chicago, IL, USA) software
      package for Chi-square test and t test. RESULTS: The operating time using self
      etching system was (122 +/- 13)s, shorter than (219 +/- 13)s using phosphate acid
      system (P < 0.05). The self-etching system used only one step to finish etching,
      adhesion and treatment of tooth surface, saving the steps of rinsing and drying.
      The retention rates of pit and fissure sealant in self-etching system and
      phosphate acid system were 97.4% and 96.2% respectively at the third month, 94.9%
      and 92.3% at the sixth month, 91.0% and 88.4% at the end of one year after
      treatment. The prevalence rate of caries in both groups had no significant
      difference (P>0.05); No caries in both groups were found in the first three
      months; In patients using self-etching system, caries decreased by 100% at the
      sixth month and by 50% at the end of one year. CONCLUSION: Adper Prompt self
      etching adhesive, with an advantage of simple operation and shorter operation
      period, is effective in bonding sealant to the enamel. The retention rates of pit
      and fissure sealant were not different between the two groups.

PMID- 17533705
TI  - [The relationship between two halitosis diagnostic methods: organoleptic test and
      VSCs measurement by a portable sulfide detector].
AB  - PURPOSE: To evaluate the relationship between organoleptic (OR) scores and
      volatile sulfur compounds (VSCs) values measured by a portable sulfide detector
      (Halimeter). METHODS: Eighty-six subjects were included into the study. The
      intensity of halitosis was evaluated by two examiners who had been trained to
      perform this procedure. A portable sulfide detector (Halimeter) was used to
      examine the values of VSCs in oral cavity. Spearman analysis was used to examine
      the relationship between the average value of organoleptic scores and VSCs
      levels. RESULTS: The Kappa value between the two examiners was 0.568, P < 0.01.
      The correlation coefficient between the average values of organoleptic scores and
      VSCs levels (including maximum and steady values) was 0.538 and 0.546, P < 0.01,
      respectively. CONCLUSIONS: The organoleptic scores were significantly related to
      VSCs values. It is suggested that Halimeter could be an assistant instrument to
      diagnose halitosis.

PMID- 17533706
TI  - [Changes in mastication efficiency before and after orthodontic treatment of
      adult skeletal angle III malocclusion].
AB  - PURPOSE: To evaluate the changes of mastication efficiency pre- and post
      treatment in adult skeletal Angle III malocclusion, and to analyze the effect of
      malocclusion on mastication efficiency. METHODS: Masticatory efficiency was
      analyzed in 60 patients with adult skeletal Angle III malocclusion pre- or post
      orthodontic treatment and 30 adults with normal occlusion as controls.
      Masticatory efficiency was measured by means of a spectrophotometer using
      Gelatin. SPSS 10.0 software package was used for Student's t test and step-wise
      regression. RESULTS: (1) Significant difference of masticatory efficiency was
      found among the three groups (P < 0.001). Multiple comparision showed significant
      difference among pre-treatment group, post-treatment group and normal controls (P
      < 0.05). (2) Step-wise regression results suggest that overjet and mandibular
      prognathism were closely related to masticatory efficiency in both pre- and post
      treatment group. CONCLUSION: Orthodontic therapy can improve masticatory function
      in patients with malocclusion.

PMID- 17533707
TI  - [Study of the consistency for three means to evaluate children's dental fear].
AB  - PURPOSE: To compare the consistency of three means evaluating children's dental
      fear. METHODS: 90 children with carious lesions into dentin in primary molars
      were divided into three groups in randomization: chemomechanical group,
      atraumatic restorative treatment (ART) and traditional rotary instrument group.
      The dental fear was evaluated by physiological measure, behavioral measure and
      projective test at the same time, and the results were compared to eluciate the
      consistency of the three methods. The data was analyzed by SPSS11.5 software
      package, using ANOVA, Chi square test and Kruskal-Wallis test, respectively.
      RESULTS: Physiological measure found the degree of dental fear in traditional
      group was the highest, and that in ART group was the lowest. Projective test
      showed the ratio of the degree of dental fear was 43.3%, 17.2% and 16.1% in
      traditional group, chemomechanical group and ART group respectively. The
      difference between traditional group and ART was significant (P < 0.05), and the
      same between traditional group and chemomecanical group (P < 0.05), while no
      significant difference was found between ART group and chemomechanical group (P >
      0.05). Behavior measure found the degree of dental fear in traditional group was
      the highest, and that in chemomechanical group was the lowest. The difference
      between traditional group and ART was significant (P < 0.05), and that between
      traditional group and chemomechanical group was significant, too (P < 0.05),
      while no significant difference was found between ART group and chemomechanical
      group (P > 0.05). CONCLUSION: The three means evaluating children's dental fear
      were of consistency.

PMID- 17533708
TI  - [A study on the state of periodontal health of 400 professional adults by random
      sampling in Shanghai].
AB  - PURPOSE: To investigate and analyze the state of periodontal health of 400 adults
      at their post and risk factors in Shanghai. METHODS: 400 subjects (249 male, 151
      female), aged from 25 to 59, were requested to fill a questionnaire. The probing
      depth (PD), clinical attachment level (CAL), tooth mobility (TM) and bleeding on
      probing(BOP) on 6 sites of each indicated tooth were measured and recorded. SAS
      6.12 software package was used for statistical analysis. RESULTS: OHI-S of
      Shanghai adults at their post was 2.16 +/- 0.99 and GI = 1.2227, indicating
      moderate gingivitis. The difference of periodontal disease among the adults at
      varied occupations in Shanghai municipality was significant. Periodontal
      destruction of the clerk group was the lightest The difference of periodontal
      disease among the adults at varied age groups in Shanghai municipality was also
      significant. Periodontal destruction of the elder group was heavier than of the
      lower age group. 146 subjects suffered from initial to moderate periodontitis.
      140 subjects suffered from advanced periodontitis. 79, 317 and 4 subjects had
      received college education, high school education and postgraduate school
      education respectively. There was no relationship between the severity of
      periodontitis and educational level. 330 out of 400 (82.5%) subjects had never
      been treated, 70 out of 400 (12.5%) had scaling,and only 3.25% of subjects had
      received regular periodontal treatment. CONCLUSION: It is very important to
      develop an education program on oral health for people in Shanghai. Supported by
      National "Tenth Five-Year" Key Project (Grant No.2004BA720A26), Research Fund of
      the Science and Technology Committee of Shanghai Municipality (Grant
      No.0352nm126) and Shanghai Leading Academic Discipline Project(Grant No.94-III
      008).

PMID- 17533709
TI  - [A three-year evaluation of the effectiveness of the school-based oral health
      education program].
AB  - PURPOSE: The aim of this study was to evaluate the oral health outcomes of a
      school-based oral health education (OHE) programme on children, mothers and
      school teachers. METHODS: The WHO Health Promoting Schools Project was applied to
      primary schoolchildren in 3 experimental and 3 control schools in Hongshan
      District, Wuhan City, with a 3-year follow-up. The data were analyzed by means of
      the SPSS/PC+ system. Differences in changes over-time between the two groups were
      compared using the independent samples t test for mean scores as the clinical
      variables while Chi-square test was applied for categorical variables. RESULTS:
      The f/F components were higher among children in the experimental group than in
      the control group (P < 0.01) and the gingival bleeding score was significantly
      lower. The increase in the proportion of children with toothbrushing at least
      twice a day was about 26% for the experimental group and 19% for the control
      group (P < 0.05); dental visits within the previous year grew higher among the
      experimental group than in the control group (P < 0.01). The proportion of
      mothers who cleaned their child's teeth weekly was significantly higher for the
      experimental group as compared to the control group (P < 0.01). CONCLUSIONS: This
      study suggested that school-based OHE had positive effects on gingival bleeding
      score and oral health behaviour in children, and as well as oral health knowledge
      and attitudes in mothers and teachers.

PMID- 17533710
TI  - [An epidemiological investigation of deciduous dental caries among 5375 preschool
      children aged between 3 to 6 years in Shenyang City].
AB  - PURPOSE: To investigate the status of dental caries of deciduous teeth among
      preschool children in Shenyang city. METHODS: According to the criteria
      recommended by the World Health Organization and The Second National Oral Health
      Investigation, the deciduous caries of 5375 preschool children aged from 3 to 6
      years were clinically examined. The mean dmft and the prevalence of dental caries
      for each age group were calculated. The results were analyzed using SPSS11.0
      software package for t test (to compare the difference between the two sample
      groups), one way ANOVA (to compare the differences among three and more sample
      groups) and chi2 test (to compare the rate of each group). RESULTS: The
      prevalence of dental caries was 71.29%. The mean dmft score was 3.88. The
      prevalence of dental caries and mean dmft increased gradually as the children
      were growing up (P < 0.05).Dental caries of the upper teeth was significantly
      more common than that of the lower teeth (P < 0.01). Most caries were minor in
      degree of severity, and mostly lie in the occlusal and proximal surface. The
      filling rate was 10.82%.As the age increase, the filling rate increased, too.
      CONCLUSION: Deciduous dental caries of preschool children was an important
      problem in Shenyang city, and the filling rate was very low. Necessary methods
      for early prevention of dental caries must be taken into consideration. Supported
      by Scientific Research Fund for College and University from Liaoning Provincial
      Education Bureau (Grant No. 20201316).

PMID- 17533711
TI  - [Effects of EMPs on growth and attachment of human BMSCs].
AB  - PURPOSE: The present study is to evaluate the effects of enamel matrix
      proteins(EMPs) on the attachment, spreading and proliferation of human bone
      marrow stromal cells(hBMSCs) in vitro. METHODS: Human BMSCs were obtained from
      human bone marrow aspiration and cultured in DMEM medium with 10% fetal bovine
      serum (FBS). EMPs was added into medium in several concentrations (50,100, 200,
      300 microg/ml) as experimental groups. BMSCs were cultured without EMPs as
      control group. Attachment ability of hBMSCs was detected by counting cell number.
      Cell spreading rates were performed at various culture times by analysis of
      micrographs taken at predetermined sites of each wells. Cell proliferation rates
      were assessed by MTT assay. Data was statistically analyzed with SAS6.12 software
      for one-way ANOVA. RESULTS: It was shown that BMSCs were cultured successfully in
      vitro. There was no significant change between the control group and experimental
      groups in cell attachment and cell spreading rate. However, the proliferation of
      BMSCs was significantly stimulated by EMPs in a dose- and time-dependent manner.
      EMPs at a concentration of 200 microg/ml significantly enhanced BMSCs
      proliferation (P < 0.05). CONCLUSION: EMPs could promote the proliferating
      ability of human BMSCs, but have no effects on its attachment and
      spreading.Supported by National "863" Project (Grant No. 2002AA205013), Shanghai
      Municipal Education Development Fund(Grant No.2002-02) and Research Fund of
      Science and Technology Committee of Shanghai Municipality (Grant No.04dz05601).

PMID- 17533712
TI  - [Effect of yishenqinghuo recipe on periodontal inflammation and immunity of rats
      with experimental periodontitis].
AB  - PURPOSE: To evaluate the effect of Yishenqinghuo recipe on periodontal
      inflammation and immunity of rats with experimental periodontitis. METHODS: 12
      months old Spague-Dawley rats were used in this study. 78 rats were randomly
      divided into 4 groups. group A: control group (with no periodontitis, fed with
      the same dosage of saline as group D); group B: model group (with periodontitis,
      fed with the same dosage of saline as group D); group C: high dosage group (with
      periodontitis, fed with double dosage of medicine as group D); group D:
      equivalent dosage group (with periodontitis, fed with clinical equivalent
      effective dosage of medicine). After being gavaged with medicine/saline for 3
      months, the periodontium was analyzed through histological slices; and the amount
      of CD4+T,CD8+T, the ratio of CD4+T/CD8+T, IL-2 and IL-1beta in peripheral blood
      were detected by flow cytometry and ELISA. All the results were analyzed by
      ANOVA, with the use of SAS 6.04 software package. RESULTS: It was found that the
      periodontal inflammation of group C and D were improved significantly; the ratio
      of CD4+T/CD8+T in peripheral blood for this 4 groups were 3.55 +/- 0.94, 2.42 +/-
      0.75, 3.23 +/- 1.14 and 3.29 +/- 0.83; the level of IL-2 and IL-1beta were
      (36.03+/- 2.63/179.04 +/- 17.29) pg/ml, (25.18 +/- 3.08/306.09 +/- 13.38) pg/ml,
      (38.44 +/- 2.58/176.33 +/- 45.38) pg/ml and (36.81 +/- 2.45/182.13 +/- 43.97)
      pg/ml. Compared with group B, the ratio of CD4+T/CD8+T for group C and D was
      significantly rised (P < 1.05); the level of IL-2 increased significantlyand IL
      1beta decreased accordingly (P < 0.01). However, there was no significant
      difference between group C and D (P > 0.05). CONCLUSION: From this study, we
      conclude that Yishenqinghuo recipe can improve the periodontal inflammation and
      adjust the immunity of rats with experimental periodontitis. Supported by
      National "Tenth Five-Year" Key Science and Technology PROject (Grant No.
      2004BA720A26) and Natural Science Foundation of Shanghai Municipality (Grant No.
      03Zr14081).

PMID- 17533713
TI  - [Osteoblastic differentiation of goat bone marrow stromal cells after AdBMP-2
      mediated transduction in vitro].
AB  - PURPOSE: To investigate the effects of adenuvirus mediated transduction with bone
      murphogenetic protein-2 on proliferation and osteoblastic differentiation of goat
      bone marrow stromal cells. METHODS: Adult goat bone marrow stromal cells were
      separated and cultured in vitro and transduced with either AdBMP-2 or AdLacZ
      gene. The transfer efficiency was calculated under microscopy. Cell proliferation
      was described by growth curve. Alkaline phosphatase staining and quantitative
      osteocalcin expression were detected after gene transduction.The data were
      analyzed by SAS6.2 software package with SNK test. RESULTS: The transfer
      efficiency reached 70% +/- 3%. No significant difference was found in cell
      proliferation among 3 groups. Alkaline phosphatase staining was more pronounced
      and osteocalcin expression was enhanced in AdBMP-2 transfered group.There was
      significant difference in osteocalcin expression between AdBMP-2 transferred
      group and the control group (P < 0.01). CONCLUSION: Adenovirus mediated
      transduction with bone morphogenetic protein-2 enhanced their osteogenic capacity
      in vitro which might be an alternative cell source for maxillofacial bone
      regeneration. Supported by National Natural Science Foundation of China (Grant
      No.30400502), Science and Technology Commission of Shanghai Municipality (Grant
      No.04dz05601, 05DJ14006, 055407034, 05QMoX14o6) and Research Grant from Shanghai
      Education Committee (Grant No. 03BC39, 04YQHB081, Y0203).

PMID- 17533714
TI  - [Re-osseointegration of peri-implantitis bone defects: an experimental study in
      dogs].
AB  - PURPOSE: To investigate the treatment methods of experimentally induced peri
      implantitis bone defects, and evaluate bone regeneration and re-osseointegration
      around implants histologically. METHODS: 30 Brinemark standard implants were
      placed in 5 Beagle dogs' mandibles to establish peri-implantitis bone defect
      model, then bone defects were randomly treated with: (1) debridement alone; (2)
      debridement plus guided bone regeneration using non-absorbable membrane; (3)
      debridement plus non-absorbable membrane associated with bone graft; (4)
      debridement plus non-absorbable membrane associated with biological activity
      glass. Peri-implant bone augmentation was observed and detected by radiography,
      fluorescence light micrography, un-decalcified bones ground section and direct
      measurement on operation. SPSS 12.0 software package was used for ANOVA, Kruskal
      Wallis test and Mann-Whiteney test. RESULTS: There were significant differences
      between four groups in peri-implant bone augmentation, bone contact level and
      bone mineralization apposition rate, P < 0.05. The group using debridement plus
      non-absorbable membrane associated with bone graft resulted in a greater amount
      of regeneration than the other treatments. CONCLUSION: Inflammation induced peri
      implant bone defects can regenerate by appropriate treatment. Supported by
      Shanghai Municipal Science and Technology Enhancement Award (Grant No.024119072).

PMID- 17533715
TI  - [Stress distribution in press-fit orthodontic microimplant bone interface].
AB  - PURPOSE: The goal of this study is to analyse the stress distribution in the
      press-fit microimplant-bone interface and its indications for immediate loading
      of orthodontic microimplant. METHODS: Three-dimensional finite element models
      were created of a 20 mm section of posterior mandible simplified in isosceles
      trapezoid shape, 30 mm in height, 10mm in upper side width, 14 mm in lower side
      width,with a single microimplant, 1.2 mm in diameter, 6 mm in length embedded in
      the bone. The cortical bone thickness was assumed as 1.6 mm. Cortical and
      cancellous bone were modeled as transversely isotropic and linearly elastic
      materials. Titanium was modeled as isotropic and linearly elastic material.
      Perfect bonding was assumed at microimplant- bone interfaces. ANSYS 9.0 finite
      element analysis software was used to generate the simplified finite element
      models of the local mandible-implant complex. 0 mm, 0.05 mm and 0.1 mm press-fit
      were arbitrarily set to the implant-bone interface to mimic the situation of
      immediate placement of microimplant. Stresses in the microimplant-bone interface
      were calculated under these "press-fit". RESULTS: Stresses distributed mainly in
      the cortical bone interface. At Omm press-fit, the stress was 0 MPa. For 0.05mm
      press-fit, the stress was 1648 MPa in mesio-distal direction, 1782MPa in occluso
      gingival direction;and for 0.1 mm, it reached 2012MPa in mesio-distal direction,
      2110MPa in occluso-gingival direction. As the "press-fit" increased, the stresses
      increased accordingly. CONCLUSION: Values of initial stress in the microimplant
      bone interface due to press-fit generated by immediately placed microimplant were
      very high in these limited and simplified three dimensional finite element
      models. It reminded us that the initial stress be taken into consideration when
      immediate loading of the microimplant is planned. Supported by Research Fund of
      Health Bureau of Zhejiang Province (2005B104).

PMID- 17533716
TI  - [A three-dimensional analysis of measuring occlusal contacts of complete
      denture].
AB  - PURPOSE: This study was designed to analyze the complete denture occlusal
      contacts by three-dimensional digital technique. METHODS: The artificial teeth
      occlusal surfaces of ten complete dentures were scanned by noncontact laser
      scanner and were reconstructed by three-dimensional technique. The locations and
      the numbers of occlusal contacts between the upper and lower full dentures were
      studied and measured in centric occlusal position, and further compared with the
      T-Scan system results by paired t test. RESULTS: (1) The results of occlusal
      contacts indicated that occlusal contacts were concentrated on molars and
      premolars and there were only 2 contacts in the area of anterior teeth. (2) There
      was no significant difference between three-dimensional reconstructive systematic
      measurement and T-Scan systematic measurement (P > 0.05). CONCLUSIONS: This study
      verified the reliability of the measurement for occlusal contacts by the three
      dimensional digital system, and may lead to a new way for occlusal contacts
      research. Supported by Shanghai Leading Academic Discipline Project (T0202).

PMID- 17533717
TI  - [Construction of tissue engineered bone by osteoblasts from canine bone marrow
      mesenchymal stem cells and Bio-Oss: an in vitro study].
AB  - PURPOSE: Using the MSCs-Bio-Oss tissue engineered bone which was constructed by
      MSCs as seed cells and the Bio-Oss calf inorganic bone grains as scaffold
      materials to determine the canine bone formation activity and the feasibility of
      Bio-Oss combined MSCs to construct tissue engineered bone. METHODS: Gybrid canine
      MSCs were dissociated, cultivated, bone formation induced and differentiated into
      osteoblast in vitro; The bone formation induced MSCs were allowed to grow onto
      Bio-Oss calf inorganic bone grains at 10(6) cell/ml, and then incubated and
      cultivated, under light pressure without other treatments. Inverted phase
      contrast microscope and scanning electron microscope were used to observe their
      morphological changes, immunofluorescent labeling of cell surface factor
      CD44,calcium nodus staining,qualitative and quantitative detection of ALP were
      carried out, and SPSS 12.0 software package was used for statistical analysis.
      RESULTS: The MSCs were uniform with compact alignment and shape of
      prosenchymatous cells, CD44's surface antigen was positive; Osteoblast activity
      was present after induction and differentiation, alizarin Bordeaux S stain of
      calcium nodus was positive, ALP's Gomori staining was also positive. ALP content
      in the experimental group were (3.307 +/- 0.217) U/g, (5.929 +/- 0.781) U/g and
      (9.739 +/- 0.547)U/g respectively at 3rd day, 7th day, 14th day after induction
      and differentiation, which were significantly different (P < 0.01) from the
      control group: (0.442 +/- 0.087) U/g, (0.581 +/- 0.027)U/g and (0.768 +/- 0.126)
      U/g; the MSCs stuck compactly on the surface of Bio-Oss, grew well, and formed
      tissue engineered bone. CONCLUSION: Using canine MSCs which were induced by bone
      formation as seed cells combined with Bio-Oss as scaffold materials to construct
      tissue engineered bone is feasible. Supported by Liaoning Provincial Natural
      Science

PMID- 17533718
TI  - [Effect of stress distribution of support tissues using attachment prostheses
      with different number of abutment].
AB  - PURPOSE: The purpose is to evaluate the effect of the stress distribution of
      support tissues when using the hinge extracoronal attachment for distal-extension
      prosthesis with different number of abutment. METHODS: Hinge extracoronal
      attachment was used for retention in distal-extension prosthesis. The 3-D
      photoelastic models of attachment of the denture of single abutment with the
      first molar or double abutments with the first molar and the second premolar were
      fabricated. Photoelastic analysis was adopted to compare the stress patterns
      generated around the support tissues with different number of abutment. RESULTS:
      Under central occlusion, most stress of the attachment of the denture with single
      abutment was concentrated at the edentulous ridge, the distal and mesial apex of
      the abutment. The results were similar with double abutments. CONCLUSIONS: In
      choosing attachment prostheses to restore the second molar distal-extension
      defects, we can choose only one tooth as abutment. The number of the abutment has
      no significant effect on the stress distribution in the supporting tissue under
      central occlusion,and there is an evenly stress distribution at the edentulous
      ridge and in the abutment. The attachment is suitable for cases with better
      alveolar membrane without high demand for abutment teeth. Supported by
      Development Fund of Science and Technology of Shanghai Municipality (Grant No.
      004119075).

PMID- 17533719
TI  - [Mechanical analysis of composite archwire applied to anterior malocclusion with
      extraction of bilateral first premolars].
AB  - PURPOSE: To optimize the structure of composite archwire applied to anterior
      malocclusion with extraction of bilateral first premolars. METHODS: The
      mandibular model was scanned by spiral CT and 30 CT images were obtained, then
      the mandible finite element model and the archwire model was respectively
      established by means of SOLIDWORKS software and ANSYS software, mechanics
      analysis and calculation were carried out. RESULTS: The force produced by
      composite archwire applied to anteriorly malocclused teeth in the model was
      greater than by TiNi shape memory alloy but smaller than stainless steel:
      F(SS)>F(CoAw)>F(NiTi); As the diameter of NiTi in the composite archwire
      increased (the diameter of stainless steel kept unchanged) , the force on the
      malocclused teeth gradually increased; As the diameter of stainless steel in the
      composite archwire increased (the diameter of NiTi kept unchanged),the force on
      the malocclused teeth increased accordingly. CONCLUSION: The rigidity of the
      composite archwire increases as the the diameter of NiTi increases; the rigidity
      of composite archwire also increases as the the diameter of the stainless steel
      increases.Supported by Research Fund of Jilin Provincial Bureau of Science and
      Technology (Grant No.20030539-3).

PMID- 17533720
TI  - [Effect of different dental polishing methods on cobalt-chromium casts surface
      roughness and accuracy].
AB  - PURPOSE: To evaluate the effect of different polishing methods on surface
      roughness and accuracy of cobalt-chromium castings. METHODS: Five polishing
      methods were compared: centrifugal barrel polishing, electrical brightening,
      grinding, grinding+centrifugal barrel polishing and grinding+electrical
      brightening. 30 specimens (30 mmx 10 mm x l.5 mm) were divided into 6 groups
      which were cast and polished for surface roughness test.30 upper complete denture
      bases were cast and divided into 6 groups. The dimensional accuracy between the
      posterior border of the upper complete denture and model at five different
      positions were determined by traveling microscope measuring method respectively
      before and after polishing. One-way ANOVA with SPSS13.0 was used for statistical
      analysis. RESULTS: Specimens polished by grinding+centrifugal barrel got the
      smoothest surface (P < 0.01) with Ra0.19 microm, compared with Ra3.38 microm
      before polishing. No significant difference of the posterior border gaps between
      the cast base and model was found (P > 0.05). CONCLUSIONS: Bases polished by
      grinding + centrifugal barrel had the smoothest surface. There is no influence of
      centrifugal barrel polishing on dimensional accuracy of cast upper base.

PMID- 17533721
TI  - [Establishment of an experimental animal model with alveolar bone defect by
      surgery in rats].
AB  - PURPOSE: To establish an animal model for experimental study of orthodontic
      treatment of alveolar bone defect and other relative research. METHODS: The
      experiment was carried out on forty SPF female Wistar rats,which were 6 weeks
      old. With the rats anaesthetized, one side of the alveolar bone in the maxillary
      first molar of the rats was removed partly. The defects were filled with Bio
      glass. The tissue slices from the defects were observed under light microscope 2
      weeks after surgery. RESULTS: Only one of the forty rats was infected after
      operation, and the survival rate was 97.5%. The wounds of the survived rats
      healed well, and new bone was found around the Bio-glass 2 weeks after operation.
      CONCLUSION: Animal model of alveolar bone defect established by surgery is simple
      and reliable, which can be used for further studies. Supported by National
      Natural Science Foundation of Shandong Province (Grant No.Y2004C13) and Medical
      Science and Technology Enhancement Award Project of Shangdong Province (Grant
      No.2005H2038).

PMID- 17533722
TI  - [Expressions of calcitonin gene -related peptide in rats with occlusal
      reconstruction].
AB  - PURPOSE: To investigate the expressions of calcitonin gene-related peptide (CGRP)
      in rats with occlusal reconstruction. METHODS: 30 Wistar male rats were randomly
      divided into 3 experimental groups and 3 control groups, 5 rats in each group.
      The molar of the right maxilla and mandible of rats in the experimental groups
      were ground to the gingival level without occlusal contact. The occlusal contact
      was recovered by stopping grounding molar of the rats in two of the experimental
      groups. The section of the disc and articular capsule Was subject to
      immunohistological study to evaluate the expressions of CGRP by using SABC
      method. Light microscope and microscopic photo analytic software were employed to
      detect calcitonin gene-related peptide-like immunoreactive (CGRP-LI) nerve fibers
      in frozen section of TMJs in 30 rats. SPSS10.0 software package were used for
      statistical analysis. RESULTS: The areas of CGRP-LI nerve fibers in unilateral
      chew group were significantly larger than those in the control group (P < 0.01, P
      < 0.05). The increment in the non-chewing side was significantly higher than that
      in the chewing side (P < 0.05). There was no significant difference in the areas
      of CGRP-LI nerve fibers between the early occlusal reconstruction group and the
      control group (P > 0.05) and there was no significant difference between the non
      chewing side and the chewing side (P > 0.05). There was significant difference in
      the areas of CGRP-LI nerve fibers between the later occlusal reconstruction group
      and the control group (P < 0.01), while no significant difference was found
      between the non-chewing side and the chewing side (P > 0.05). CONCLUSION: The
      expressions of CGRP can recover normal in early occlusal reconstruction but not
      in later occlusal reconstruction.CGRP might participate in the histopathogenesis
      of temporomandibular joint disorders. Supported by Research Fund from Science and
      Technology Bureau of Taian City (Grant No.2003-52).

PMID- 17533723
TI  - [Induction of mouse embryonic stem cells forming odontoblast-like cells by co
      culture with pulp fibroblast].
AB  - PURPOSE: To investigate the methods of induction of mouse embryonic stem cells to
      differentiate into odontoblast-like cells by co-culture with pulp fibroblast.
      METHODS: By suspension culture, embryonic stem cells were induced to form
      embryoid bodies. Then the cells from embryoid bodies were co-cultured with pulp
      fibroblast in Transwell system for differentiation toward odontoblast-like cells.
      RESULTS: By RT-PCR analysis, embryoid body cells gave rise to the cell population
      expressing DSPP, a specific odontoblast cell marker, after 10 days of co-culture
      with pulp fibroblast and the expression of DSPP was enhanced after 15 days of co
      culture. On the other hand, the expression of DSPP was not detected in the
      isolately cultured embryoid body cells. CONCLUSIONS: Embryonic stem cells can be
      induced into odontoblast-like cells by co-culture with pulp fibroblast. Supported
      by Science and Technology Development Fund of Shanghai Municipality (Grant No.
      03ZR14027).

PMID- 17533724
TI  - [The effect of core binding factor alpha1 on transcriptional regulation of mouse
      dentin sialophosphoprotein].
AB  - PURPOSE: To investigate the effect of core binding factor alpha1 (cbfalpha1) on
      transcriptional regulation of mouse dentin sialophosphoprotein (DSPP) gene.
      METHODS: The MDPC-23 cells and the segment of nt -2475bp to +53bp were chosen.
      After co-transfected, the MDPC-23 cells were measured for luciferase activity
      using the dual luciferase reporter assay system. The results were analyzed by
      SPSS10.0 software package. RESULTS: In MDPC-23 cells, the luciferase activity was
      significantly low in the group of co-transfected with pGL3-Enhancer-2.6K and
      pcDNA3-cbalpha1 than the group of pGL3-Enhancer-2.6K and pcDNA3 (P < 0.01).
      CONCLUSION: Cbfalpha1 can reduce the activity of DSPP promoter including the
      segment of nt-2475bp to +53bp in MDPC-23 cells. This suggests that cbfalpha1 can
      transcriptionally regulate the expression of DSPP. Supported by National Natural
      Science Foundation of China (Grant No.30271418).

PMID- 17533725
TI  - [Analysis of the peer reviewed papers published in Shanghai Journal of
      Stomatology between 2001 and 2005].
AB  - PURPOSE: To analyze the characteristics of publications of Shanghai Journal of
      Stomatology (SJS) between 2001 and 2005. METHODS: By use of literature metrology,
      a comprehensive analysis of the publications of Shanghai Journal of Stomatology
      from 2001 to 2005 was made. RESULTS: The number of articles published from 2001
      to 2005 in Shanghai Journal of Stomatology was 208, the authors were from 4
      countries and 23 states or provinces. The cooperative articles accounted for
      90.40%, and the average paper author cooperating degree was 3.46. Authors with
      middle and high professional positions accounted for 90.93%. Authors with
      doctorate degree and master degree accounted for 72.59%, the average cited
      references were 8.11, with references from English literatures accounting for
      65.28%. CONCLUSIONS: Shanghai Journal of Stomatology is one of the most important
      information sources on stomatology.

PMID- 17533726
TI  - [Advances in the research of bisphosphonate-associated osteonecrosis of the
      jaws].
AB  - Recently, some reports indicate that osteonecrosis of the jaws could occur after
      taking drugs containing hisphosphonates, including alendronate, pamidronate and
      zolendronate, which are widely used to treat osteoporosis and metastatic skeletal
      lesions in clinic.More and more attentions were given to this new oral
      complication. This article summarizes some advances in clinical manifestation,
      diagnosis, prevention and therapy of bisphosphonate -associated osteonecrosis of
      the jaws as well as the possible mechanisms involved.

PMID- 17533727
TI  - [Progress of histological study on anchorage implants].
AB  - The study and the application of anchorage implants had attracted more and more
      attention from the orthodontists. This article reviewed the histological studies
      involving the implants used as orthodontic anchorage and found tendency to be
      micro-implants and self-drilling. The new concepts of osseointegration between
      micro-implant and bone, immediate loading, long-term loading and periodontal
      repair after injury from anchorage implant evoked challenges to the conventional
      understanding.

PMID- 17533728
TI  - [Samuel Pessoa: a scientific trajectory in the context of public health campaigns
      and developmentalism Brazil].
AB  - The article discusses the professional experience of Samuel Pessoa (1898-1976),
      parasitologist and physician, within the framework of the Getuilio Vargas
      government's political and administrative reforms. Pessoa's trajectory shows that
      growing bureaucratization of all state sectors, presented new challenges to
      enforcers of public health policies. Nevertheless, this trend did not imply a
      radical sterilization of the public health campaign approach endorsed by the
      medical elite in the 1920s. An examination of Pessoa's career reveals how
      Brazil's various 'sanitary schools' did not necessarily espouse antagonistic
      views; rather, Pessoa himself proved a recognized proponent of
      'developmentalism', influenced by a more technicist public health model, yet did
      not turn his back on the 1920s discussions, particularly when it came to his
      interest in sanitary initiatives in rural Brazil.

PMID- 17533729
TI  - British medicine in the Peruvian Andes: the travels of Archibald Smith M.D. (1820
      1870).
AB  - This article traces the travels of the Scottish physician Archibald Smith through
      the Peruvian Andes between the 1820s and 1860s. Despite his prominent role in the
      nineteenth-century Peruvian medical scene, almost nothing has been written on
      Archibald Smith. By exploring Smith's medical activities, publications, and
      debates, this article intends to uncover unexplored areas of Peruvian medical
      history, such as the animosity between local and foreign physicians during the
      post-Independence war era and the important role played by medical geography as a
      scientific discipline for redefining ethnical and regional issues.

PMID- 17533730
TI  - [Polytechnicians or mathmaticians?].
AB  - The first mathematics research were realized in Brazil by people with
      polytechnical formation, that means, coming from Polytechnic. This work presents
      biographical drafts and the main contributions of elevens from these pioneers.
      The worked in military Schools and Polytechnic. And also in the faculties of
      philosophy that started to appear in the country since 1930. In these group of
      eleven mathematicians one can differentiated between the ones who were
      sympathetic with positivism and the ones who were not.

PMID- 17533731
TI  - [Science and history in the report by the First Republic's Comissao Exploradora
      do Planalto Central].
AB  - The idea of moving Brazil's capital to the Central Plateau reappeared in the
      early days of the Republic, having been defended one century earlier by the
      Viscount of Porto Seguro. Headed by Luiz Cruls, director of Brazil's National
      Observatory, a commission was formed in 1892 to stake out the area where the new
      capital would stand. The expedition's 1896 report found space in Brazil's main
      vehicles of public opinion; it was reviewed in newspapers and also in articles
      published in Revista do Instituto Historico e Geografico Brasileiro, the
      Brazilian Institute for History and Geography's journal. A number of issues then
      of concern to certain sectors of Brazilian society converge in the body of the
      report, including the healthiness of Brazil's climate for European immigrants,
      the definition of the country's borders, and territorial integration.

PMID- 17533732
TI  - [Paje: reconstruction and survival].
AB  - On the Brazilian coast and in the Amazon, pajes played a role in the resolution
      of problems from the sixteenth through eighteenth centuries, although curing
      diseases was only one of their functions. Colonial laws were designed to ensure
      the legitimacy of the conquest, and right from their earliest long-term contacts
      with the natives, missionaries and settlers saw the pajes as major roadblocks to
      proposed changes. Therefore, from the times of the colony through the empire and
      the republic, ecclesiastic and lay leaders worked together to bring about the
      physical and moral downfall of the pajes. The ethnic and linguistic changes that
      wiped out hundreds of languages have always hampered efforts to characterize the
      figure of the paje in clear terms. With European specialists making their
      influence felt, pajes have been confused with Asian shamans. But the paje has
      reconstructed himself and survived. Despite the violent transformations caused by
      Salesian missionaries in the upper Negro River area, pajes there continue
      exercising their powers even today.

PMID- 17533733
TI  - [Selling health! A new look at old-time pharmacy almanacs].
AB  - Offering images of pharmaceutical products and marketing strategies, pharmacy
      almanacs are a valuable source when researching the history of medications. The
      article analyzes the idea of science that was presented in these almanacs and
      demonstrates how this research source is pertinent to the history both of science
      and of advertising in Brazil.

PMID- 17533734
TI  - [The healthcare system for slaves in nineteenth-century Brazil: disease,
      institutions, and treatment practices].
AB  - Although the nineteenth century saw numerous attempts to deter the slave trade,
      it was also the period when Brazil imported the greatest number of slaves in its
      history. The conditions under which slaves were transported, worked, and lived
      were largely responsible for their state of health. Yet this topic barely makes
      an appearance in the field of history, and many disputed points remain to be
      settled. My research cross-references sources and topics in order to gather data
      on the hygienic lives of nineteenth-century slaves. By analyzing archival
      documents from hospitals, notary public offices, and church bodies, iconographic
      sources, and the medical literature, I have retrieved information that can be
      used towards writing a history of the healthcare system available to slaves.

PMID- 17533735
TI  - [The mouse ovarian surface epithelium cells (MOSE) transformation induced by c
      myc/K-ras in].
AB  - OBJECTIVE: To study the function of c-myc and K-ras in tumorigenesis of ovarian
      cancer. METHODS: K-ras and/or c-myc cDNAs were introduced into mouse ovarian
      surface epithelium cells (MOSE) using recombinant Moloney retroviral vectors. The
      resulting MOSE cells were studied by cell proliferation assays, the ability to
      form colonies in soft agarose, matrigel invasion assays and tumorigenicity assays
      in nude mice. RESULTS: K-ras and c-myc can be easily delivered to the normal MOSE
      cells by recombinant retroviruses. mRNA and protein of the target genes can be
      detected by RT-PCR and Western blot. Cell proliferation assays showed that MOSE
      Ras cells and MOSE-RM cells (MOSE-Ras/Myc) grew more rapidly than parental cells
      (MOSE) and MOSE-Myc cells (P <0.01). In addtition, MOSE-RM cells grew more
      rapidly than MOSE-Ras cells (P <0. 05). Cell colony formation assays showed that
      while MOSE-Ras and MOSE-RM cells can form colonies in soft-agarose, the MOSE-Myc
      and MOSE cells did not. Matrigel invasion assays showed that MOSE-Ras and MOSE-RM
      cells have invasion ability, but not MOSE-Myc ascites and the control MOSE cells.
      Xenograft experiments showed that MOSE-Ras and MOSE-RM cells were able to form
      tumors in nude mice following intraperitoneal injection. Tumors were not observed
      in animals injected with either MOSE-Myc or MOSE cells. CONCLUSION: The
      recombinant Moloney retroviral system is a highly efficient and convenient method
      for introducing and expressing foreign genes in murine surface epithelial cell
      cultures. In this model, expression of K-ras alone is sufficient to generate
      tumorigenic MOSE, however expression of c-myc in conjunction with K-ras results
      in cells with a higher index of malignancy. Based on the assays described in this
      report, expression of c-myc alone can not transform MOSE cultures although it
      does play a role in cooperation with K-ras.

PMID- 17533736
TI  - [Expression of ER alpha in chemically induced MDA-MB-435 cells and its
      responsiveness to endocrine].
AB  - OBJECTIVE: To investigate the expression of ER alpha in chemically induced, ER
      alpha-negative human breast cancer MDA-MB-435 cells and its restoration of the
      responsiveness to endocrine therapy. METHODS: MDA-MB-435 cells were treated with
      HDAC inhibitor trichostatin A(TSA)and DNMT1 inhibitor 5-AZA-CdR (AZA). The mRNA
      level of ER alpha, PR and PS2 in treated MDA-MB-435 cells was detected by RT-PCR.
      The WST-8 (water-soluble tetrazolium salt-8) method was used to analyze the
      proliferation rate of the cells. Xenograft in female nude mice was used to
      further explore the change of proliferation rate of treated MDA-MB-435 cells in
      vivo. RESULTS: After treatment with AZA and TSA, mRNA expression of ER alpha, PR
      and pS2 was up-regulated in MDA-MB-435 cells. The mRNA level of ER alpha was the
      hightest when MDA-MB-435 cells were treated with 2.5 micromol/L AZA and 100 ng/ml
      TSA. The treated MDA-MB-435 cells showed different proliferation rate in various
      media containing different concentration of estrodial. The MDA-MB-435 cells
      showed down-regulated proliferation rate after treatment with the combination of
      2.5 micromol/L AZA and 100 ng/ml TSA, and 4-OH tamoxifen could suppress the
      growth rate of the induced MD-MBA-435 cells but not the untreated cells. The
      treated MDA-MB-435 cells showed slower proliferation rate than that of untreated
      cells in vivo (P <0. 01), and the proliferation rate of the treated MDA-MB-435
      cells became lower when the nude mice were deprived of estrogen by castration (P
      <0. 01). CONCLUSION: After treatment with TSA and AZA, ER alpha-negative MDA-MB
      435 cells can express functional ER alpha and regain responsiveness to estrogen
      both in vitro and in vivo. HDAC inhibitor and DNMT1 inhibitor may play an
      important role in restoration of sensitivity of ER alpha-negative breast cancers
      to endocrine therapy.

PMID- 17533737
TI  - [Inhibitory effect of AG490 on invasion and metastasis of human pancreatic cancer
      cells in vitro].
AB  - OBJECTIVE: To investigate the effect and mechanism of blockade of STAT3 signaling
      pathway by JAK specific inhibitor-AG490 on invasion and metastasis of human
      highly metastatic pancreatic cancer line SW1990 in vitro. METHODS: AG490 was
      added into the culture media for SW1990 cells. The invasion ability of SW1990
      cells was determined by cell invasion assay kit. Western blot was performed to
      detect the protein expression of the STAT3, phosphorylated STAT3 (p-STAT3), MMP-2
      and VEGF. RT-PCR was performed to detect the mRNA expression of the MMP-2 and
      VEGF. RESULTS: 20 micromol/L AG490 significantly inhibited the invasion ability
      of SW1990 cells and the inhibitory rate of invasion ability was (77.67 +/- 7.79)
      %. The use of AG490 not only markedly reduced the protein expression of p-STAT3,
      MMP-2 and VEGF, but also greatly reduced the mRNA expression of MMP-2 and VEGF.
      CONCLUSION: Blocking STAT3 activation with AG490 can inhibit the invasion and
      metastasis ability of pancreatic cancer cells in vitro through down-regulation of
      MMP-2 and VEGF expression. Blocking STAT3 signaling pathway may provide a novel
      strategy in prevention of invasion and metastasis of pancreatic cancer.

PMID- 17533738
TI  - [Demethylation of estrogen receptor gene and its re-expression in estrogen
      receptor-negative breast].
AB  - OBJECTIVE: To investigate the correlation between the lack of estrogen receptor
      (ER) gene expression and hypermethylation of ER gene, and detect whether re
      expressed ER protein is activated. METHODS: The methylation status of ER gene
      promoter in the ER-negative breast cancer cells was evaluated by methylation
      specific PCR (MSP) and genomic sequencing. The expression of ER and progesterone
      receptor (PR) mRNA as well as the production of ER protein were detected by RT
      PCR and Western blot method, respectively. MTI assay was used to examine the
      function of re-expressed ER protein. RESULTS: The ER gene promoter was highly
      methylated, while ER mRNA and ER protein were not expressed in the ER-negative
      breast cell line MDA-MB-231. The ER-negative breast cells treated with
      demethylating agent 5 -aza-2'-deoxycytidine (5-AZA-2'-deoxyC) restored the
      expression of ER mRNA and ER protein. Expression of the endogenous ER-responsive
      PR gene was activated and the methylation of ER gene was simultaneously
      decreased. After MDA-MB-231 was treated with 5-AZA-2'-deoxyC, the protein of ER
      was re-expressed and the growth of cells treated with tamoxifen were inhibited
      significantly (P < 0.05). CONCLUSION: inactivation of ER gene has a close
      relationship with the abnormal methylation of ER gene promoter. 5-AZA-2'-deoxyC
      may effectively cause demethylation and restore functional expression of ER
      silenced by aberrant hypermethylation. The result may offer a new measure and
      theory for breast cancer patients with ER-negative expression to receive
      endocrine therapies.

PMID- 17533739
TI  - [Influence of compound actinidia root mixture on Cx43 expression in tumor-bearing
      nude mice].

PMID- 17533740
TI  - [Prognostic molecular classification of breast cancers based on gene expression
      profiling].
AB  - OBJECTIVE: To screen a set of gene markers related to metastasis and prognosis of
      breast cancer by comparison of gene expression profiles of primary breast cancers
      with distant metastasis to the cases without distant metastasis within 3 years
      follow-up, and to explore the clinical significance of those gene expression in
      prognostic molecular classification of breast cancer patients. METHODS: 5 cases
      with distant metastasis and 5 cases without distant metastasis within 3 years
      follow-up were used as training cases to compare their gene expression profiles
      by Oligo microarray hybridization containing 21 329 human functional genes. K
      mean supervised cluster was done for 10 training cases and additional 20 testing
      cases based on the set of differential genes. "Leave-one-out" was used to
      eliminate useless genes to obtain optimal gene set that was used for prognostic
      molecular classification of breast cancer patients. RESULTS: The different genes
      screened out from gene expression profiling of primary breast cancers with and
      without distant metastasis could classify breast cancer patients into two sub
      groups. All patients with distant metastasis were included in the "poor prognosis
      group" (7/10), whereas there were no case showing distant metastasis in the "good
      prognosis group" (0/20), with a statistically significant difference by exact
      probability test (P =0. 03). In the set of 104 optimal genes, all 5 genes
      involved in cell adhesion and migration were up-regulated in cases with distant
      metastasis, all 2 genes related to immune response of host were down-regulated,
      11 genes related to cell growth and metabolism were up-regulated and 14 down
      regulated, and 15 genes related to cell signal transduction were significantly
      changed. CONCLUSION: A set of genes involved in cell adhesion and migration, cell
      growth and metabolism, immune response mechanism, cell signal transduction were
      screened out by comparing gene expression profiles of primary breast cancers with
      and without distant metastasis within 3 years follow-up, showing highlight in
      prognostic molecular classification of breast cancer patients and hopeful would
      benefit to choose patient-tailored therapy strategies.

PMID- 17533741
TI  - [Serum proteomic patterns may assist the diagnosis of solitary pulmonary
      nodules].
AB  - OBJECTIVE: To screen relatively specific biomarkers in serum from lung
      adenocarcinoma patients by surface-enhanced laser desorption and ionization time
      of flight mass spectrometry (SELDI-TOFMS), and to investigate the clinical value
      of SELDI-TOF-MS in differentiation of benign from malignant solitary pulmonary
      nodules (SPN). METHODS: Serum samples from 71 lung adenocarcinoma patients and 71
      healthy volunteers with matched gender, age and history of smoking were analyzed
      using WCX2 ProteinChip to screen potential biomarkers. 28 patients received
      surgical treatment among total 53 patients with SPN. The clinical value of SELDI
      TOF-MS in differentiation of benign from malignant solitary pulmonary nodules was
      evaluated by pathological diagnosis. RESULTS: Five highly expressed potential
      biomarkers were identified with the relative molecular weights of 4047.79 Da,
      4203.99 Da, 4959. 81 Da, 5329. 30 Da and 7760.12 Da. The postoperative pathologic
      diagnosis was lung adenocarcinoma in 24 patients with SPN, validating the
      clinical value of the 5 potential biomarkers. CONCLUSION: SELDI-TOF-MS technology
      is a quick, easy, convenient, and high-throughput analyzing method capable of
      screening several relatively specific potential biomarkers from the serum of lung
      adenocarcinoma patients and may have attractive clinic value in differentiation
      of solitary pulmonary nodules.

PMID- 17533742
TI  - [Significance and mechanisms of overexpression of PAK1 gene in epithelial ovarian
      neoplasms].
AB  - OBJECTIVE: To investigate the significance and mechanisms of overexpression of
      p21-activated kinase 1 gene (PAK1) in epithelial ovarian neoplasms. METHODS:
      Immunohistochemistry, fluorescence in situ hybridization and terminal
      deoxynucleotidyl transferase-mediated dUTP nick end-labeling methods were used to
      examine the protein expression and amplification of PAK1 and cell apoptosis in 30
      benign ovarian adenomas, 20 borderline tumors and 80 ovarian carcinomas by tissue
      microarray. RESULTS: In immunohistochemistry study, overexpression of PAK1
      protein was observed in 7 (25.9%) informative benign ovarian adenomas, 7 (36.8%)
      borderline tumors and 53 (68.8%) ovarian carcinomas. A significant inverse
      correlation of PAK1 overexpression and cell apoptosis was observed in these
      epithelial ovarian neoplasm cohorts (P = 0.002). In addition, 27/31 (87.1%)
      poorly differentiated (G3) carcinomas showed overexpression of PAK1, the
      frequency was significantly higher than that in tumors of G1 - G2 (26/46, 56.5% ,
      P =0.01). In fluorescence in situ hybridization study, only 2 (4.7%) informative
      ovarian carcinomas showed amplification of PAK1 gene. None of the borderline and
      benign ovarian tumors showed PAK1 amplification. CONCLUSION: Overexpression of
      PAK1 protein may be involved in the tumorigenesis of epithelial ovarian neoplasms
      and it is associated closely with the malignant histological phenotype of ovarian
      carcinomas. Mechanism other than gene amplification of PAK1 may play a more
      important role in the regulation of protein expression of PAK1 in ovarian tumors.

PMID- 17533743
TI  - [Genomic imbalance and chromosome disorders in hepatoblastoma].
AB  - OBJECTIVE: To establish stable techniques of comparative genomic hybridization
      (CGH) and apply them to elucidate the genetic characteristics of hepatoblastoma
      (HB), and to explore the characteristics and clinical significance of loss of
      heterozygosity (LOH) at 1p36 in HB. METHODS: CGH was employed to detect the
      genomic imbalance (DNA loss or amplification) in 20 cases of HB, and PCR-simple
      repeated sequence polymorphism was employed in 30 cases of HB to detect the loss
      of heterozygosity for 6 satellites at chromosome 1p36. RESULTS: There were
      different chromosome variations for each HB. chromosome amplification was
      frequently seen in 1q, 2q,2p, 8q, 8p, 12q and 22q. Chromosome loss was often seen
      in 1p, 4q, 4p, 16q, 17p and 18q. The frequency of LOH at 6 loci on chromosome 1
      was 63.3% totally (19/30), with the highest D1S199 (66.7%) and D1S450 next to it
      (46.7%). CONCLUSION: There were chromosome zones with DNA amplification or loss
      in hepatoblastoma. There are extensive LOH at 1p36 in hepatoblastoma. The
      corresponding amplification of oncogene and loss of antioncogene may take part in
      the development of hepatoblastoma.

PMID- 17533744
TI  - [Effects of ST1571 on the development of dendritic cells derived from bone marrow
      mononuclear cells in patients with chronic myeloid leukemia].
AB  - OBJECTIVE: To investigate the effects of ST1571 on the development of dendritic
      cells (DC) derived from bone marrow mononuclear cells of patients with chronic
      myeloid leukemia (CML). METHODS: Bone marrow mononuclear cells (BMMNC) from CML
      patients and healthy volunteers were cultured initially using multiple cytokine
      combinations as follows: recombinant human granulocyte/ macrophage colony
      stimulating-factor (rhGM-CSF) plus recombinant human interleukin-4 (rhIL-4) as
      CML and normal control groups, rhGM-CSF plus rhIL-4 and ST1571 as CML
      experimental groups, and from day 8 recombinant human tumor necrosis factor-alpha
      ( rhTNF-alpha) was added to stimulate DC maturation. The morphologic features of
      cells were observed by Wright's staining and phenotypes were assessed by flow
      cytometry. Cytogenetic analysis was performed by fluorescence in-situ
      hybridization (FISH), and the antigen-presenting function was assayed by mixed
      lymphocyte reaction (MLR). The concentration of VEGF was detected by ELISA.
      RESULTS: CML experimental groups treated with STI571 displayed morphological
      features similar to those of control groups with delicate membrane projections.
      However, in comparison with the CML control groups, the CML experimental groups
      showed an increased expression of CD80, CD86, CD83 and HLA-DR and showed more
      intense abilities of allogeneic antigen presentation, which were similar to those
      of normal control groups. FISH confirmed that DCs of both CML, groups were of
      leukemic origin. The concentration of VEGF was dramatically reduced in CML
      experimental groups. CONCLUSION: In vitro, STI571 promotes the
      activation/maturation of DCs derived from BMMNCs of patients with CMI, and
      decreases VEGF production by the leukemic cells. The promotion of DC maturation
      may be partially due to decreased inhibitory effect of VEGF.

PMID- 17533745
TI  - [18F-FDG imaging by coincidence circuit SPECT with low-dose CT in preoperative
      assessment of pulmonary lesions].
AB  - OBJECTIVE: To assess the clinical diagnostic value of 18F-FDG imaging by
      coincidence circuit SPECT with low-dose CT in differential diagnosis of pulmonary
      lesions and mediastinal lymph node involvement, which can not be definitely
      diagnosed based on regular CT image in patients with non-small-cell lung cancer
      (NSCLC). METHODS: By using GE-Millennium VG with Hawkeye, 18F-FDG imaging was
      carried out in 48 patients with suspected lung cancer. Clinical value of 18F-FDG
      imaging for diagnosing malignancy was evaluated through comparison with the final
      pathological results. Mediastinal lymph node involvement was also assessed
      through lesion-by-lesion comparison with pathologic results in 74 lymph node
      regions from 24 patients. RESULTS: Final pathologic diagnoses of these patients
      were 36 malignancies consisting of 20 adenocarcinomas, 12 squamous cell
      carcinomas, 3 small cell carcinomas and I large cell carcinoma; 12 benign tumors
      including 6 pneumonias, 2 tuberculosis, 2 hamatomas, 1 cyst and 1 neurofibroma.
      Of 48 patients, uptake of 18F-FDG in the chest was found to be abnormal in 40.
      Correct diagnosis were made in 34 malignancies and 6 false positive lesions were
      excluded based on morphology and 18F-FDG uptake status of the lesion. There were
      6 false positive and 2 false negative cases. Furthermore, extrathoracic
      metastases which were not showed on previous CT image in 4 patients including one
      in the adrenal gland and 3 in the bone were detected by 18F-FDG imaging. The
      sensitivity, specificity and accuracy of the 18F-FDG imaging for differentiating
      malignant tumor from benign was 94.4%, 50.0% and 83.3%, respectively. Squamous
      cell carcinoma was found to uptake more FDG than adenocarcinoma. For
      determination of mediastinal lymph node involvement, the sensitivity, specificity
      and accuracy of 18F-FDG imaging was 57.9% , 90.9% and 82.4%, respectively through
      lesion-by-lesion comparison; whereas, which was 61.5%, 81.8% and 70.8%,
      respectively, based on case-by-case comparison. CONCLUSION: 18F-FDG imaging by
      coincidence circuit SPECT with low-dose CT is quite helpful in differential
      diagnosis for patient with undetermined lesion on regular CT image, but it is
      limited for staging of lung cancer in the patients with non-small cell lung
      cancer.

PMID- 17533746
TI  - [Value of high-resolution ultrasonography in differential diagnosis of cervical
      cystic lesions].
AB  - OBJECTIVE: To analyze ultrasonographic features of the different kinds of
      cervical cystic lesions, and propose differential diagnostic standard for these
      lesions based on the evidence of high resolution ultrasonography. METHODS: The
      clinical data of 107 patients with different kinds of cervical cystic lesions
      were analyzed. The role of gray scale and colour Doppler sonography for such
      lesions was prospectively studied. RESULTS: The rate of accuracy for benign
      cervical cystic lesions was 91.1% (92/101), however, it was only 16.7% (1/6) for
      malignant cervical cystic lesions. CONCLUSION: High-resolution ultrasonography is
      effective and simple in differential diagnosis of different kinds of cervical
      cystic lesions, especially for benign ones.

PMID- 17533747
TI  - [Effect of hypoxic radiosensitizer sodium glycididazole on long-term result of
      radiotherapy for nasopharyngeal carcinoma].
AB  - OBJECTIVE: To evaluate the long-term effect of sodium glycididazole (CMNa) as a
      hypoxic radiosensitizer on the radiotherapy for nasopharyngeal carcinoma.
      METHODS: Between May 1999 and May 2002, 211 patients with pathologically
      confirmed nasopharyngeal carcinoma were randomized into group-A treated by
      radiotherapy plus CMNa or group-B by radiotherapy alone. The staging was
      determined according to 92' Fuzhou staging systerm. The type, procession and
      dosage of radiotherapy were identical in both groups. The early adverse effect
      grade was assessed based on the CTC2.0 criteria and the late adverse effects were
      evaluated according to the RTOG/EORTC criteria. The median follow-up time was 52
      months. All the data was analyzed by the SPSS 13.0 software. Characteristics and
      adverse events of these patients were compared between the two groups using t
      test and the Wilcoxin rank sum test. Time-to-event curves were estimated using
      the Kaplan-Meier method. The prognostic parameters were analyzed using univariate
      analysis and the Cox multivariate regression analysis. RESULTS: The clinical data
      of the two groups were comparable. The 3-year survival was 88.4% in group-A,
      while 75.2% in group-B, with a statistically significant difference between two
      groups (P = 0.010). Univariate analysis showed that the 3-year survival was
      statistically correlated with N-staging ((N0-1, 86.9%, N2-3 73.8%, P < 0.001), T
      staging (T1-2 85.6%, T3-4 79.3%, P = 0.014), TNM staging (P = 0.039), and whether
      using CMNa or not during rediotherapy (Group-A 88.4%, Group-B 75.2%, P = 0.010).
      The 5-year recurrence-free survival, 5-year metastasis-free survival and 5-year
      overall survival were 75.8%, 74.9% and 77.7% in Group-A, while 63.0%, 63.0% and
      62.4% in Group-B with a statistically significant difference between two groups
      (0.013, 0.022 and 0.010, respectively). If stratified in the subgroups, the
      overall survival of stage III - IV patients was statistically different between
      group A and B (P = 0.009), however, not of stage I - II patients (P = 0.502). Cox
      multivariate regression analysis showed that the independent prognostic
      parameters for survival were N-stage (RR = 3.288) , T-stage (RR = 2.147) and use
      of CMNa during rediotherapy (RR = 0.407). However, there was no statistically
      significant difference between two groups in acute or late adverse effects on
      nervous system or heart, which suggested that use of CMNa during radiotherapy
      would not aggravate the toxicity caused by radiotherapy. CONCLUSION: Sodium
      glycididazole is well tolerable effective as a hypoxic radiosensitizer, which can
      improve the efficacy of radiotherapy and the long-term result of nasopharyngeal
      carcinom a patients, especially for the stage III - IV patients.

PMID- 17533748
TI  - [Comparison of primary tongue carcinoma with second primary tongue carcinoma
      after radiotherapy for nasopharynx cancer].
AB  - OBJECTIVE: To investigate the clinical characteristics and prognosis of second
      primary tumor of tongue (SPTr) after nasopharyngeal carcinoma (NPCR) treated with
      radiotherapy. METHODS: Clinical data of 53 patients with SP7T after NPCR (group
      A) and 252 patients with primary tongue carcinoma (group B) were analyzed
      retrospectively with regard to clinical characteristics and survival rate (Kaplan
      Meier); and multivariate analysis was performed using Cox proportional hazards
      model. RESULTS: There was no significant difference between group A and group B (
      P > 0. 05) in the presenting age, sex, tumor size, cTNM stage, tumor
      differentiation and the rate of distant metastasis. The overall 5-year survival
      rates were 41.6% in group A and 56.3% in group B (chi2 = 4.40, P = 0.0359) with a
      statistically significant difference between two groups. The differences of tumor
      location (chi2 = 61.18, P = 0.000) and rate of clinical (cN+, chi2 = 6.846, P =
      0.009) or pathological lymph node metastasis (pN+, X2 = 3.993, P = 0.046) were
      also statistically significant between group A and group B, respectively.
      Multivariate analysis showed that age at presence, cTNM stage and with or without
      neck lymph node dissection were independent risk factors affecting survival.
      CONCLUSION: Second primary tongue carcinoma after radiotherapy for nasopharyngeal
      carcinoma is likely to occur on the dorsal aspect of the tongue with worse
      prognosis but with a lower rate of lymph node metastasis than that of primary
      tongue carcinoma. However, radiotherapy history is not an independent influencing
      factor on prognosis. Surgical resection or combined modality therapy may give a
      better prognosis.

PMID- 17533749
TI  - [Analysis of combinated transcatheter hepatic artery chemoembolization and
      factors affecting the prognosis in patients with primary hepatic carcinoma].
AB  - OBJECTIVE: To evaluate the combinated transcatheter hepatic artery
      chemoembolization (TACE) and analyse the factors affecting prognosis in patients
      with primary hepatic carcinoma. METHODS: 141 consecutive patients with primary
      hepatic carcinoma were treated, including 125 men and 16 women (mean age, 52
      years; age range, 21 - 76 years). Combinated TACE procedures included TACE, TACE
      followed by surgical resection, TACE and percutaneous ethanol injection (PEI) and
      transcatheter hepatic artery infusion (TAI). The factors included sex, age, ALT,
      AFP, HBsAg, liver function (Child's system), the way of treatment, tumor size and
      number, serum albumin, portal cancerous thrombus, pathological type of tumors,
      and HBeAg. The Cox's regression analysis model was used to analyse the factors
      affecting the prognosis. P < 0.05 means statistically significant difference.
      RESULTS: The total median survival time was 19 months and mean survival time
      23.59 months. The total survival rates of 1, 2, 3, 5 years were 63.9%, 44.5%,
      25.8% and 7.4%, respectively. Multivariable analysis revealed significant
      prognostic factors as follows: age, liver function, the way of treatment, portal
      cancerous thrombus and pathological types of tumors (chi2 = 45.993, P = 0.0001).
      CONCLUSION: The combinated TACE procedure is safe and effective. In this study, 5
      factors directly influencing the prognosis are age, liver function, portal
      cancerous thrombus and pathological types of tumors are risk prognostic factors,
      and the way of treatment is a protective factor (chi2 = 45.993, chi2 = 0.0001).

PMID- 17533750
TI  - [Phase I study of docetaxel combined with carboplatin in patients with non-small
      cell lung cancer].
AB  - OBJECTIVE: To determine the maximum tolerated dose (MTU) and dose-limiting
      toxicity (DLT) of Docetaxel and Carboplatin in patients with non-small cell lung
      cancer. METHODS: Docetaxel was given at escalating doses until MTD was determined
      from the initial dose of 65 mg/m2 to 75 mg/m2, 85 mg/ m2 on dl. Carboplatin was
      targeted to an area under the plasma concentration curve of 5 using Calver's
      equation on dl. The treatment cycle was repeated every 3 weeks. RESULTS: 16
      patients received TXT and CBP for total of 54 courses (median four courses).
      Neutropenia was the dose-limiting toxicity. The MTD of TXT is 85 mg/m2.
      CONCLUSION: We recommend TXT 75 mg/m2 on d1 and CBP with a target AUC of 5 on d1,
      3weeks repeated for chemotherapy in naive patients with NSCLC.

PMID- 17533751
TI  - [Suggestions to doctors of western medicine on the application of anti-neoplastic
      Chinese patent drugs].

PMID- 17533752
TI  - From sticks to coffee-maker: mastery of tools and technology by human and non
      human primates.

PMID- 17533753
TI  - Neural correlates of state estimation in visually guided movements: an event
      related fMRI study.
AB  - State estimation of self-movement, based on both motor commands and sensory
      feedback, has been suggested as essential to human movement control to compensate
      for inherent feedback delays in sensorimotor loops. The present study
      investigated the neural basis for state estimation of human movement using event
      related functional magnetic resonance imaging (fMRI). Participants traced
      visually presented curves with a computer mouse, and an artificial delay was
      introduced to visual feedback. Motor performance and brain activities during
      movements were measured. Experiment 1 investigated brain activations that were
      significantly correlated with visual feedback delay and motor error by
      parametrically manipulating visual feedback delay. Activation of the right
      posterior parietal cortex (PPC) was positively correlated with motor error,
      whereas activation of the right temporo-parietal junction (TPJ) was observed only
      in the group with a smaller increase in motor error with increased visual
      feedback delay. Experiment 2 involved parametric analysis of motor performance
      while controlling mouse movement speed during the task. Activity in the right TPJ
      showed a significant positive correlation with motor performance under the
      delayed visual feedback condition. In addition, activity of the PPC was greater
      when motor error was presented visually. These results suggest that the PPC plays
      a significant role in evaluating visuomotor prediction error, while the TPJ is
      involved in state estimation of self-movement during visually guided movements.

PMID- 17533754
TI  - Differences between actual and imagined usage of chopsticks: an fMRI study.
AB  - We examined neural basis underlying tool-use behavior to discuss whether or not
      the usage of a well-learned tool has a specific route. Regional cerebral blood
      flow was measured in healthy Japanese subjects using functional magnetic
      resonance imaging (fMRI) during object pick-up using chopsticks, object pick-up
      using the hand, pantomiming the use of chopsticks, imagining the use of
      chopsticks, and imagining the use of the hand. First, the left inferior parietal
      lobule (IPL) was found to selectively contribute to tasks requiring explicit
      retrieval of tool-related hand movements that were pantomiming task and imagery
      task. This finding provides supporting evidence for the ideomotor apraxia (IMA)
      model proposed by Buxbaum (2001). However, departing from Buxbaum's (2001)
      proposal, the actual use of a well-learned tool displays distinct processing
      routes to those for pantomime and imagining. A comparison of these tasks revealed
      that activation in the lateral part of the right cerebellum increased during
      execution of tool-use, and this activity was considered to reflect the internal
      model for tools proposed by Imamizu et al. (2000, 2003).

PMID- 17533755
TI  - A new notation system of object manipulation in the nesting-cup task for
      chimpanzees and humans.
AB  - The nesting-cup task has been used to assess cognitive capability in humans as
      well as non-human primates. Previous studies have attempted to highlight
      interesting aspects of behavior by constructing and assessing various categories
      of manipulation. The present study introduces a new notation system for
      describing manipulation in nesting-cup tasks in the form of sequential codes.
      Following this notation, the entire process of manipulating cups can be divided
      into a sequence of behavioral segments. Each segment corresponds to a single
      manipulation of a cup, recorded as two numerical and one letter codes indicating
      object, location, and action, respectively. These codes describe the full extent
      of the subjects' manipulation, which can thus be traced retrospectively in its
      entirety by decoding the behavioral segments from the sequence. The subjects were
      three infant chimpanzees, three adult chimpanzees, and two human children.
      Segment-based analysis revealed developmental changes in the use of three
      strategies (pairing, pot, and subassembly), which previous studies have used as
      reliable indicators of cognitive development. Subassembly, regarded as the most
      advanced strategy for combining cups in human development, is defined as the
      placing of a previously constructed structure consisting of two or more cups into
      or onto another cup or cup structure. The three infant chimpanzees and two adult
      chimpanzees rarely showed subassembly, in contrast with frequent use by
      experienced adult chimpanzees and humans. Analysis of transition in cup state
      revealed a dynamic process in terms of progression and regression within a trial.
      The tendency to show progressive patterns of transition was related to the use of
      the subassembly strategy in both humans and chimpanzees. In addition, a case
      study of nine-cup manipulation by a chimpanzee is reported through sequential
      codes. Taken together, these data clearly demonstrate the potential of the
      proposed notation system in describing subjects' performance in nesting-cup
      tasks.

PMID- 17533756
TI  - Tool use and related errors in ideational apraxia: the quantitative simulation of
      patient error profiles.
AB  - The behaviour of ideational apraxic patients on simple tasks involving multiple
      objects is typically marked by a variety of errors. While some of these errors
      concern the sequential organisation of action through time, many relate to the
      misuse of, or failure to use, necessary or appropriate tools. In this paper we
      apply the computational model of Cooper and Shallice (2000) to five standard
      multiple object tasks used in clinical assessment and demonstrate how, when
      lesioned, the model can account for the error profiles of two ideational apraxic
      patients discussed by Rumiati et al. (2001). Application of the model to the
      multiple object tasks demonstrates the generality of the model, while the account
      of the error profiles extends previous work (Cooper et al., 2005) in which
      ideational apraxia was argued to arise from a generalised disturbance of object
      representations that are held to trigger action schemas.

PMID- 17533757
TI  - Reorganization of brain activity for multiple internal models after short but
      intensive training.
AB  - Internal models are neural mechanisms that can mimic the input-output properties
      of controlled objects. Our studies have shown that: 1) an internal model for a
      novel tool is acquired in the cerebellum (Imamizu et al., 2000); 2) internal
      models are modularly organized in the cerebellum (Imamizu et al., 2003); 3) their
      outputs are sent to the premotor regions after learning (Tamada et al., 1999);
      and 4) the prefrontal and parietal regions contribute to the blending of the
      outputs (Imamizu et al., 2004). Here, we investigated changes in global neural
      networks resulting from the acquisition of a new internal model. Human subjects
      manipulated three types of rotating joystick whose cursor appeared at a position
      rotated 60 degrees, 110 degrees, or 160 degrees around the screen's center. In a
      pre-test after long-term training (5 days) for the 60 degrees and 160 degrees
      joysticks, brain activation was scanned during manipulation of the three
      joysticks. The subjects were then trained for the 110 degrees for only 25 min. In
      a post-test, activation was scanned using the same method as the pre-test.
      Comparisons of the post-test to the pre-test revealed that the volume of
      activation decreased in most of the regions where activation for the three
      rotations was observed. However, there was an increase in volume at a marginally
      significant level (p < .08) only in the inferior-lateral cerebellum and only for
      the 110 degrees joystick. In the cerebral cortex, activation related to 110
      degrees decreased in the prefrontal and parietal regions but increased in the
      premotor and supplementary motor area (SMA) regions. These results can be
      explained by a model in which outputs of the 60 degrees and 160 degrees internal
      models are blended by prefrontal and parietal regions to cope with the novel 110
      degrees joystick before the 25-minute training; after the acquisition within the
      cerebellum of an internal model for the 110 degrees, output is directly sent to
      the premotor and SMA regions, and activation in these regions increases.

PMID- 17533758
TI  - Cerebellar activity evoked by common tool-use execution and imagery tasks: an
      fMRI study.
AB  - The purpose of this study is to identify the functional brain networks activated
      in relation to actual tool-use in humans. Although previous studies have
      identified brain activity related to tool-use gestures (Moll et al., 2000), they
      did not investigate the brain activity involved in such tool-use. We investigated
      brain activity using functional magnetic resonance imaging (fMRI) while human
      subjects mentally imagined using sixteen common tools and while they actually
      used them. Brain activity for both actual and imagined tool-use was found in the
      posterior part of the parietal cortex, in the supplementary motor area, and in
      the cerebellum. Under imagined tool-use conditions, we found brain activity in
      the premotor and right pars opercularis. Under actual tool-use conditions, we
      found it in the primary motor area, in the thalamus, and in the left pars
      opercularis. Our precise analysis in the cerebellum indicated that activity
      evoked by imagery was located significantly more lateral to that evoked by actual
      use. We found a relationship between activity in the tool imagery and execution
      conditions by comparing their t-value-weighted centroid of activation
      coordinates. Moreover, for half of the subjects the spatial distribution pattern
      for each tool was similar, suggesting that neural mechanisms contributing to
      skillful tool-use are modularly organized in the cerebellum.

PMID- 17533759
TI  - Ideomotor apraxia and functional ability.
AB  - The impact of ideomotor apraxia (IMA) on functional ability has been a relatively
      neglected topic in research. This has been due to the continued focus on
      performance on gesture imitation and pantomime of tool-use, together with
      widespread acceptance of anecdotal evidence that IMA has no effect when directly
      manipulating objects. An increasing number of studies have shown that IMA does in
      fact result in increased clumsiness when handling objects and may contribute to
      disability in everyday life. However the effect seems relatively mild compared to
      the stark abnormalities on gesture imitation and pantomime. The conventional
      explanation for this is that the cues provided by naturalistic contexts improve
      retrieval of action representations, but an alternative account concerns task
      specific cognitive demands. Performance on simple prehensile tasks can be
      successfully guided by physical affordances whereas motor tasks may be failed if
      they require the support of memory or problem solving ability. A central deficit
      in IMA may be impaired postural representation causing inability to solve the
      problem of how to manipulate objects where neither affordance nor memory can
      dictate action. However, this account still fails to explain fully the patterns
      of error seen on complex naturalistic tasks such as dressing. Future research
      needs to further our understanding of how IMA maps on to disability, which will
      have implications for theory building and for therapeutic intervention.

PMID- 17533760
TI  - What puts the how in where? Tool use and the divided visual streams hypothesis.
AB  - An influential theory suggests that the dorsal (occipito-parietal) visual stream
      computes representations of objects for purposes of guiding actions (determining
      'how') independently of ventral (occipito-temporal) stream processes supporting
      object recognition and semantic processing (determining 'what'). Yet, the ability
      of the dorsal stream alone to account for one of the most common forms of human
      action, tool use, is limited. While experience-dependent modifications to
      existing dorsal stream representations may explain simple tool use behaviors
      (e.g., using sticks to extend reach) found among a variety of species, skillful
      use of manipulable artifacts (e.g., cups, hammers, pencils) requires in addition
      access to semantic representations of objects' functions and uses. Functional
      neuroimaging suggests that this latter information is represented in a left
      lateralized network of temporal, frontal and parietal areas. I submit that the
      well-established dominance of the human left hemisphere in the representation of
      familiar skills stems from the ability for this acquired knowledge to influence
      the organization of actions within the dorsal pathway.

PMID- 17533761
TI  - Degraded semantic knowledge and accurate object use.
AB  - In the present paper we report the performance on object use and on semantic
      tasks of two patients, D.L. with probable semantic dementia, and A.M. with an
      atypical onset of dementia of Alzheimer, assessed twice two years apart. In
      particular, we investigated whether the patients' ability to use objects degraded
      as a function of their semantic knowledge about those objects. Results from the
      two assessments in 2002 and in 2004 confirmed that both patients had a selective
      loss of the lexical-semantic knowledge, despite a relative preservation of the
      other cognitive abilities including object use. This pattern of results suggests
      that semantic knowledge is not necessarily involved in the correct use of
      objects.

PMID- 17533762
TI  - Functional organization of monkey brain for abstract operation.
AB  - When humans manipulate a control device under operational rules, with the goal of
      indirectly controlling a remote tool to achieve a desired outcome, they may rely
      on the power of internal representation to organize individual moves of the
      controller and tool into a set of sequences by mapping the motor space among
      hand, controller and tool. We recently used functional brain imaging (PET) to
      investigate activations in monkey brain associated with joystick-controlled
      remote operation of a shovel to obtain food. Activated areas included the
      prefrontal cortex, posterior parietal cortex and cerebellum, regardless of the
      rules relating movements of the joystick to those of the shovel (Obayashi et al.,
      2004). If those areas are engaged in the mental manipulation of internal
      representation, then we should expect brain activity in the same regions during
      any similar remote operation, even with different controllers and/or operational
      rules. To address the above hypothesis in the current study, we used PET to
      measure regional cerebral blood flow (rCBF) of two monkeys during a task in which
      they were required to control a shovel remotely (to fetch a food pellet) by
      manipulating dual dials. Compared to unplanned movement of the dials, the active
      dual-dial operation was associated with robust activation of the prefrontal
      cortex, higher-order motor cortex, posterior parietal cortex and cerebellum,
      quite similar to that observed during remote operation with a joystick. The
      present study suggests that monkeys might be able to organize abstract sequential
      operations according to learned rules, and perhaps indeed to have insight into
      the nature of the causal relationships, implying the existence of a relatively
      sophisticated system of internal representation in the absence of language. The
      fact that the present results are consistent with our previous PET studies
      strengthens the view that the underlying mechanism for implicit manipulation of
      internal representations may involve a cerebro-cerebellar neural circuit
      including the frontal and parietal cortex.

PMID- 17533763
TI  - Bisecting lines with different tools in right brain damaged patients: the role of
      action programming and sensory feedback in modulating spatial remapping.
AB  - In a first experiment we studied, through a line bisection task, (a) the
      frequency of the selective disruption of far or near space representations in a
      group of 28 right brain-damaged patients and (b) the effect of tool use on line
      bisection error in far and near space in order to clarify whether the kind of
      action performed by the subject influences the extension of space representation,
      as suggested by previous studies. In a second experiment, carried out on two
      neglect patients, we asked whether the representation of "near" and "far" space
      depends on the sensory feedback during the execution of the action or whether it
      is independent on sensory feedback and more related to the action programmed as a
      consequence of the kind of tool used. Our data show (a) that dissociations
      between far and near space neglect are a frequent observation in right brain
      damaged patients and that most of these patients are able to recode space
      representations when tools change the spatial relation between the agent's body
      and the target object; (b) that spatial remapping can be elicited by the kind of
      action associated to the tool used and by the sensory feedback (either visual or
      proprioceptive) available during the execution of the task. In particular,
      presence of tactile proprioceptive feedback elicited remapping of far space into
      near space, whereas absence of visual feedback induced remapping of near space
      into far space.

PMID- 17533764
TI  - Left inferior parietal representations for skilled hand-object interactions:
      evidence from stroke and corticobasal degeneration.
AB  - Patients with ideomotor apraxia (IM) are frequently more impaired in the
      production and imitation of object-related (transitive) than non-object-related,
      symbolic (intransitive) gestures, but reasons for this dissociation, and its
      anatomical underpinnings, remain unclear. Our theoretical model of praxis
      (Buxbaum, 2001) postulates that left inferior parietal lobe (IPL) gesture
      representations store information about postures and movements of the body and
      hand for skillful manipulation of familiar objects; in contrast, bilateral fronto
      parietal dynamic calculations provide constantly-updated information about the
      current position and movement of the body and hand for both familiar and novel,
      transitive and intransitive movements. This account predicts distinct patterns of
      IM in patients with left IPL damage versus bilateral fronto-parietal involvement.
      Consistent with predictions, 16 stroke patients with left IPL damage were more
      impaired with transitive than intransitive gestures, whereas 4 patients with
      bilateral fronto-parietal damage due to corticobasal degeneration (CBD) were not
      [F (1, 18) = 8.5 p < .01]. Additionally, the hand posture component of transitive
      gestures was the most impaired aspect of gesture in CVA, but tended to be the
      least impaired aspect of gesture in CBD [F (3, 54) = 5.1, p < .005]. Finally, CVA
      patients were more impaired with transitive hand postures than meaningless or
      intransitive hand postures, whereas CBD patients showed the opposite pattern.
      These data indicate that the left IPL mediates representations of skilled hand
      object interactions, as distinct from dynamic coding of the body in space, and
      suggest that the IPL maps between representations of object identity in the
      ventral stream and spatial body representations mediated by the dorsal system.

PMID- 17533765
TI  - The impact of dysexecutive syndrome on use of tools and technical devices.
AB  - We present two studies aimed at elucidating why patients with dysexecutive
      syndrome encounter difficulties with the use of tools and technical devices. Two
      different groups of patients with dysexecutive syndrome took part in them. Their
      results were compared with those of two groups of normal controls and in the
      first study also with those of patients with posterior left or right brain
      lesions. The first study contrasted single step with multi-step actions and
      explored the role of novelty and consecutive demands on problem solving.
      Dysexecutive patients encountered problems only with the multi-step actions. The
      rank order of strength of impairment corresponded to the presumed rank order of
      demands on problem solving, but the analysis of individual results demonstrated
      high variability of this pattern which moreover could not be fully replicated
      when the same tests were applied in the second study. The second study pursued
      the hypothesis that maintenance of goals and constraints in working memory is the
      crucial factor for difficulties of dysexecutive patients. Support for this
      hypothesis was less ambiguous, but as this study did not include patients with
      posterior lesions it remains open whether this factor is specific for
      dysexecutive syndrome and prefrontal brain damage or applies to brain damage
      regardless of its location.

PMID- 17533766
TI  - Dynamic size-change of peri-hand space following tool-use: determinants and
      spatial characteristics revealed through cross-modal extinction.
AB  - In human and non human primates, evidence has been reported supporting the idea
      that near peripersonal space is represented through integrated multisensory
      processing. In humans, the interaction between near peripersonal space
      representation and action execution can be revealed in brain damaged patients
      through the use of tools that, by extending the reachable space, modify the
      strength of visual-tactile extinction, thus showing that tool-mediated actions
      modify the multisensory coding of near peripersonal space. For example, following
      the use of a rake to retrieve distant, otherwise non reachable objects, the peri
      hand multisensory area has been documented to extend to include the distal part
      of a rake (Farne and Ladavas, 2000). The re-sizing of peri-hand space seems to be
      selective for tool-use, as directional motor activity alone (i.e., pointing
      without the tool) and visual/proprioceptive experience alone (protracted passive
      exposure to the tool) does not vary the extent of the visual-tactile peri-hand
      space (Farne et al., 2005a). Moreover, the amount of dynamic re-sizing varies
      with the length of the used tool, and is specifically centred on the functionally
      relevant part of the tool (Farne et al., 2005b). Here, besides reviewing and
      discussing these results, we report new evidence, based on a single-case study,
      supporting the idea that dynamic re-sizing of peri-hand space consists of a real
      spatial extension of the visual-tactile integrative area along the tool axis.

PMID- 17533767
TI  - Task-dependent selection of grasp kinematics and stiffness in human object
      manipulation.
AB  - Object manipulation with the hand is a complex task. The task has redundancies at
      many levels, allowing many possibilities for the selection of grasp points, the
      orientation and posture of the hand, the forces to be applied at each fingertip
      and the impedance properties of the hand. Despite this inherent complexity,
      humans perform object manipulation nearly effortlessly. This article presents
      experimental findings of how humans grasp and manipulate objects, and examines
      the compatibility of grasps selected for specific tasks. This is accomplished by
      looking at the velocity transmission and force transmission ellipsoids, which
      represent the transmission ratios of the corresponding quantity from the joints
      to the object, as well as the stiffness ellipsoid which represents the
      directional stiffness of the grasp. These ellipsoids allow visualization of the
      grasp Jacobian and grasp stiffness matrices. The results show that the
      orientation of the ellipsoids can be related to salient task requirements.

PMID- 17533768
TI  - Grounding object concepts in perception and action: evidence from fMRI studies of
      tools.
AB  - Studies of categories of objects, including tools, have spurred the development
      of the sensory-motor model of object concept representation. According to this
      model, information about objects is represented in the same neural subsystems
      that are active when we perceive and use them. In turn, this model has provided
      insight into the brain mechanisms of tool use. For tools, three types of
      information are especially important for identification: the characteristic
      motion with which they move (such as the up and down motion of a hammer), their
      visual form, and the way that they are manipulated. Evidence from
      neuropsychological, non-human primates, and neuroimaging studies suggest a
      mapping between specific brain regions and these fundamental identifying
      properties of tools. We focus on neuroimaging studies of the left posterior
      middle temporal gyrus. This brain region is active both when subjects perceive
      moving tools and when they answer questions about tools, and is responsive to the
      type of visual motion characteristic of tools: rigid, unarticulated motion. We
      describe a simple model that explains how low-level receptive field properties
      like those known to exist in area MT/V5 could give rise to the high-level
      category-related representations observed in functional imaging experiments.

PMID- 17533770
TI  - Sibling kinnections: a clinical visitation program.
AB  - The growing literature on sibling relationships throughout their lifespans is of
      great importance to those working in the child welfare system, and in adoption
      services in particular. Sibling bonds are important to all of us, but they are
      particularly vital to children from disorganized or dysfunctional families. These
      relationships assume even greater importance when children from these families
      enter the care system. Supporting and sustaining these sibling bonds should be,
      and most often is, a priority throughout the child welfare system, with practice
      literature providing guidelines for arranging and sustaining sibling contact.
      However, children in the care system may also have dysfunctional sibling
      relationships as a result of their early experiences, and sibling visitation
      alone may not be enough to ensure a healthy, long-lasting relationship among
      siblings. Some form of sibling therapy, or 'clinically supervised visitation,'
      may be required to help children remove the barriers to form mutually satisfying
      relationships and to reinforce life-long relationships with each other.

PMID- 17533769
TI  - Tool-use: capturing multisensory spatial attention or extending multisensory
      peripersonal space?
AB  - The active and skilful use of tools has been claimed to lead to the "extension"
      of the visual receptive fields of single neurons representing peripersonal space-
      the visual space immediately surrounding one's body parts. While this hypothesis
      provides an attractive and potentially powerful explanation for one neural basis
      of tool-use behaviours in human and nonhuman primates, a number of competing
      hypotheses for the reported behavioural effects of tool-use have not yet been
      subjected to empirical test. Here, we report five behavioural experiments in
      healthy human participants (n=120) involving the effects of tool-use on visual
      tactile interactions in peripersonal space. Specifically, we address the
      possibility that the use of only a single tool, which is typical of many
      neuropsychological studies of tool-use, induces a spatial allocation of attention
      towards the side where the tool is held. Participants' tactile discrimination
      responses were more strongly affected by visual stimuli presented on the right
      side when they held a single tool on the right, compared to visual stimuli
      presented on the left. When [corrected] two tools were held, one in each hand,
      this spatial effect disappeared. Our results are incompatible with the hypothesis
      that tool-use extends peripersonal space, and suggest instead that the use and/or
      manipulation of [corrected] tools results in an automatic multisensory shift of
      spatial attention to the side of space where the tip of the tool is actively
      held. These results have implications for many of the cognitive neuroscientific
      studies of tool-use published to date.

PMID- 17533771
TI  - Adoption Now: a joint initiative of New York's courts and child welfare system.
AB  - In November 2002, Chief Judge Judith Kaye attended the National Adoption Day
      festivities in Albany County and New York County (Manhattan). Although pleased
      that 600 adoptions were being finalized statewide on this special day, she was
      concerned to learn more than 6,000 other children were free for adoption but had
      not yet found permanent families. Judge Kaye reached out to New York State Office
      of Children and Family Services (OCFS) Commissioner John A. Johnson and New York
      City Administration for Children's Services (ACS) then-Commissioner William Bell
      to come together and begin a discussion to identify and resolve systemic barriers
      to adoption. At a press conference in May 2003, Chief Judge Kaye, Governor
      Pataki, New York City Mayor Bloomberg, and Judges and Commissioners representing
      counties from across the state announced the Adoption Now initiative that set a
      goal of finalizing adoptions for 5,000 children (3800 in New York City and 1200
      upstate) by the end of 2003.

PMID- 17533772
TI  - Making MEPA-IEP work: tools for professionals.
AB  - The Multiethnic Placement Act of 1994 and the Interethnic Adoption Provisions of
      1996 (MEPA-IEP) require states to develop plans that "provide for the diligent
      recruitment of potential foster and adoptive families that reflect the ethnic and
      racial diversity of children in the state for whom foster and adoptive homes are
      needed." This paper explores the background of MEPA-IEP, describes the disparate
      outcomes for minority children in the child welfare system, and identifies agency
      challenges in finding permanent families for African American children. Tools are
      provided for successfully recruiting families while following MEPA-IEP and
      avoiding potentially discriminatory practices in placement decisionmaking.

PMID- 17533773
TI  - Assessing lesbian and gay prospective foster and adoptive families: a focus on
      the home study process.
AB  - Foster care and adoption by gay men and lesbians is not a new phenomenon.
      Children and youth have always been placed by states and public agencies in homes
      with gay and lesbian parents. Some gay men and lesbians have fostered or adopted
      children independently from private agencies or have made private adoption
      arrangements with individual birthmothers, while others have fostered or adopted
      through the public system. Drawing on research literature, practice wisdom from
      31 years of child welfare experiences, and case examples, this article offers
      child welfare professionals guidelines for competent assessment with prospective
      foster or adoptive parents who identify as lesbian or gay.

PMID- 17533774
TI  - Strengthening adoption practice, listening to adoptive families.
AB  - In-depth interviews with 500 adoptive families who received postadoption services
      through Virginia's Adoptive Family Preservation (AFP) program paint a richly
      detailed picture of the challenges adoptive families face and what they need to
      sustain adoption for many years after finalization. Findings document the need
      for support in a variety of forms, including respite, counseling, and
      information. Numerous implications for strengthening adoption practice through
      effective training and technical assistance are discussed.

PMID- 17533775
TI  - Supporting child welfare supervisors to improve worker retention.
AB  - Recent child welfare research has identified supervisors as key to retaining
      qualified and committed workers. This paper describes implementation of a
      federally funded child welfare training initiative designed to improve worker
      retention largely through developing, implementing, and evaluating a statewide
      supervisor training program in a Midwestern state. Unique to this collaborative
      effort was involving all child welfare supervisors in identifying needed content
      components, developing competencies, and conducting self-assessments.

PMID- 17533776
TI  - A comparative evaluation of preservice training of kinship and nonkinship
      foster/adoptive families.
AB  - In 2003, Idaho selected the Foster PRIDE/ Adopt PRIDE preservice training and
      resource family development program. PRIDE participants (n = 228) completed a pre
      and posttest survey based on the PRIDE training competencies in 2004-2005.
      Results indicate that PRIDE is an effective training and resource family
      development program. Providing and evaluating foster/ adoptive parent preservice
      training programs can assist child welfare programs in making a positive
      difference in the lives of families and children involved in the child welfare
      system while increased cost-savings by retaining foster/adoptive families over
      time.

PMID- 17533777
TI  - Home study methods for evaluating prospective resource families: history, current
      challenges, and promising approaches.
AB  - Every state requires a home study before the placement of foster children for
      adoption. This article examines the history of home studies, presents results
      from expert interviews on the changing processes and purposes of home studies,
      and explores current challenges for the field. The article also introduces the
      Structured Analysis Family Evaluation (SAFE), a uniform home study format that
      encourages consistent family evaluations across workers, agencies, and
      jurisdictions. The article clarifies how SAFE may address challenges facing
      foster care and adoption practice.

PMID- 17533778
TI  - Medicare. Part D: Prescription drug coverage.

PMID- 17533779
TI  - Gold, diamonds, and pearls and the art of alchemy: nursing care of the aging
      patient.

PMID- 17533780
TI  - Following through with IOLs.

PMID- 17533781
TI  - Normal flora of the external eye.

PMID- 17533782
TI  - Dry eye symptoms following cataract surgery.
AB  - This randomized, controlled clinical study demonstrates the development of dry
      eye-type symptoms after routine cataract extraction, and shows that topical
      cyclosporine ophthalmic emulsion can reduce the occurrence of these symptoms
      after cataract surgery. Based on these results, a regimen of pre- and
      postoperative topical cyclosporine should be considered for cataract patients who
      have dry eyes or who are at risk of developing dry eye. This paper presents the
      study methodology and results, and discusses implications for care of cataract
      patients so as to improve the quality of vision after surgery and to maximize
      patient satisfaction with the procedure.

PMID- 17533783
TI  - Mast cell stabilizers for the relief of allergic conjunctivitis.

PMID- 17533784
TI  - A promise kept.

PMID- 17533785
TI  - Planning for community benefit: the past is prologue.

PMID- 17533786
TI  - Human dignity: an "energizing vision" of health care.

PMID- 17533787
TI  - Pastoral care: prepared to make a difference.

PMID- 17533788
TI  - What are acquired rights in Canon Law?

PMID- 17533789
TI  - Health reform overview: where are we headed?

PMID- 17533790
TI  - Covering the uninsured problem is America's problem. The current health care
      system makes no moral or economic sense.

PMID- 17533791
TI  - Health care access for all. Viewed from Catholic social teaching, the current
      U.S. situation represents a moral failure.

PMID- 17533792
TI  - Reform's three essential elements. To be effective, insurance coverage must be
      adequate, affordable, and available.

PMID- 17533793
TI  - Toward the "tipping point". A new coalition of groups is working quietly to
      reform U.S. health care.

PMID- 17533794
TI  - Transformational leadership. Model encourages leaders to transcend personal
      ambition.

PMID- 17533795
TI  - Regaining minorities' trust. A clinic project in a Philadelphia neighborhood may
      serve as a paradigm for Catholic hospitals.

PMID- 17533796
TI  - Artificial nutrition and hydration and the Catholic tradition. The Terri Schiavo
      case had even members of Congress debating the issue.

PMID- 17533797
TI  - Global health and Catholic social commitment.

PMID- 17533798
TI  - Global health as a factor in economic and social stability.

PMID- 17533799
TI  - Health reform on the horizon. A White House veteran shares her insights on the
      future of health care reform.

PMID- 17533800
TI  - Telemedicine extends healing ministry and offers innovative "patient safety net".

PMID- 17533801
TI  - Using national alcohol screening day to deliver personalized feedback: a pilot
      study.
AB  - The current study tested the effectiveness of using National Alcohol Screening
      Day (NASD) to deliver personalized feedback via mail. At-risk NASD participants
      were assigned to either personalized or generic feedback conditions and attended
      a 4-week follow-up. Results failed to find any group differences on alcohol
      related variables. However, participants in the personalized group reported a
      reduction in the maximum number of drinks consumed on one occasion. The
      personalized group also had a more accurate view of the amount of alcohol their
      peers consumed. NASD is a vehicle to efficiently deliver feedback to individuals
      about their alcohol use; however, more research is needed to determine the types
      of feedback that would be most effective.

PMID- 17533802
TI  - Secondhand tobacco smoke and municipal smokefree ordinances: attitudes of
      restaurant and bar owners and managers.
AB  - Understanding the attitudes of restaurant and bar owners and managers toward a
      smokefree city ordinance can contribute greatly to the success of a smokefree
      policy campaign. While local opposition to a smokefree policy always arises from
      restaurant and bar owners, this study of restaurant and bar owners and managers
      in two Midwestern cities reveals that over two-thirds (67.1%) support a smokefree
      restaurant policy, and over 40% support a policy that would include bars.
      Moreover, most prefer the local government to require the city to be smokefree
      rather than choose to go smokefree on their own: only 1 in 5 would even consider
      going smokefree independently. The study explains that this is primarily due to
      widespread and unfounded fears of economic loss. Finally, the article recommends
      that education campaigns encouraging individual restaurants to go smokefree would
      be a far less effective strategy than persuading a municipal government to enact
      a smokefree ordinance.

PMID- 17533804
TI  - Implementation fidelity in a teacher-led alcohol use prevention curriculum.
AB  - There is now ample evidence that teachers tend to make substantial modifications
      to both the prescribed content and methods of the curricula they administer, and
      that such modifications are likely to attenuate curricula effects. We examine the
      fidelity with which teachers implement "Protecting You, Protecting Me," an
      underage alcohol use prevention curriculum. Findings suggest that while teachers
      attempted to implement most sections of a lesson, the lessons taught were
      consistently--and often extensively--adapted. We conclude that since teachers are
      likely to continue to modify lessons, curriculum developers and trainers should
      enhance their understanding of how prevention curricula are taught under real
      world conditions, help teachers to reinforce key curriculum concepts, and
      consider modifying those curricular sections that teachers are adapting with
      greatest frequency.

PMID- 17533803
TI  - Community reactions to campaigns addressing crystal methamphetamine use among gay
      and bisexual men in New York City.
AB  - Crystal methamphetamine (aka "crystal meth") use with high-risk sex has become an
      emerging health problem for gay and bisexual men in New York City since the late
      1990s. Public health campaigns were eventually developed to encourage gay and
      bisexual men to avoid or reconsider using crystal meth. Reactions to three
      campaigns were measured with a cross-sectional survey administered in 2004. Among
      an ethnically-diverse sample of 971 gay and bisexual men, 61.8% reported seeing
      the campaigns. Those who reported ever using crystal meth, recent use, and recent
      use with sex were significantly more likely to have seen the campaigns. In
      general, white men, HIV-negative men, and men not currently using crystal meth
      responded more positively to the campaigns than their counterparts; yet, more men
      of color reported having discussions with partners and friends about their
      crystal use as a result of these campaigns. Implications for researchers and
      practitioners are discussed.

PMID- 17533805
TI  - Substitution of marijuana for alcohol: the role of perceived access and harm.
AB  - Research has shown significant declines in gateway drug use among participants in
      a school/community substance abuse prevention intervention in a midwestern,
      suburban school district (Lohrmann, Alter, Greene, & Younoszai, 2005). Though
      still at or below national levels, student marijuana use was not impacted as
      positively. The current study investigated the possibility that efforts to
      prevent alcohol use resulted in an unintentional substitution effect thereby
      increasing marijuana use. Factors including perceived access to alcohol and
      marijuana, along with perceived harm associated with alcohol and marijuana use,
      were examined to determine their role in marijuana use. Findings revealed a
      relationship between perceived access to and perceptions of harm associated with
      marijuana and its use that depended on the level of perceived access to and harm
      associated with alcohol.

PMID- 17533806
TI  - A preliminary investigation of the components of a curriculum for the preparation
      of master's-level addiction counselors.
AB  - This study identified the preliminary curriculum components for the preparation
      of graduate-level addiction counselors. A review of the related literature
      revealed no agreed upon standards for post baccalaureate instruction of addiction
      counseling. The Delphi method was used to establish curriculum items from a list
      of 198 previously identified work behaviors associated with graduate-level
      addiction counseling. A panel of 28 addiction counseling experts responded to
      three administrations of an evolving questionnaire and reached consensus on a
      final list of 89 curriculum items. Consensus of expert judgments was corroborated
      by a post hoc multivariate of analysis of variance (MANOVA) that revealed no
      significant differences in ratings of importance among panelist subgroups.

PMID- 17533807
TI  - Liver nuclear and microsomal CYP2E1-mediated metabolism of xenobiotics in rats
      chronically drinking an alcohol-containing liquid diet.
AB  - In previous studies from our laboratory, the presence in highly purified liver
      nuclei of metabolic pathways for processing ethanol (EtOH), N
      nitrosodimethylamine (NDMA), carbon tetrachloride and chloroform was reported.
      All these chemicals are known to be metabolized in liver microsomes, via
      cytochrome P450 2E1 (CYP2E)-mediated processes. In the present work we checked
      whether rat liver nuclei from rats chronically drinking an alcohol-containing
      liquid diet exhibited an enhanced ability to metabolize chemicals known to
      require CYP2E1 participation for given metabolic transformations. The
      nicotinamide adenosine dinucleotide phosphate (NADPH)-requiring metabolism of p
      nitrophenol to p-nitrocathecol; the activation of carbon tetrachloride to
      trichloromethyl radicals, covalently binding to proteins; and the ring
      hydroxylation of aniline and o-toluidine were studied. Comparison of the obtained
      nuclear activities against the one present in the microsomal counterpart, and
      their respective response to the EtOH inductive effect after repetitive exposure
      to it, was studied. The obtained results showed that rat liver nuclei exhibited
      less p-nitrophenol hydroxylase activity than microsomes, but it was inducible by
      repetitive alcohol drinking to equivalent levels of those of microsomes from
      control animals. Nuclei exhibited the ability to activate CCl4, which was
      significantly enhanced by alcohol drinking. Aniline was ring hydroxylated in
      liver microsomes but not in nuclei from either control or EtOH-treated animals.
      In contrast, nuclei and microsomes metabolized o-toluidine to ring hydroxylated
      products. They are considered less toxic in nature but other authors reported a
      genotoxic effect for one of them. The production of the ring hydroxylated
      metabolites was enhanced by repetitive EtOH drinking. Results suggest that
      nuclear metabolism of xenobiotics might be relevant for either activations or
      detoxications mediated by CYP2E1 and that repetitive exposure to EtOH might
      significantly modulate those processes.

PMID- 17533808
TI  - Effect of chronic fluorosis on lipid peroxidation and histology of lung tissues
      in first and second generation rats.
AB  - This experiment was designed to investigate the lipid peroxidation and
      histological effects of chronic fluorosis on first and second generation rat lung
      tissues. Sixteen, virgin, female Wistar rats were mated with eight males (2:1)
      for approximately 12 h to obtain first-generation rats. Pregnant rats were
      divided into two experimental groups (control and fluoride supplemented). The
      pregnant rats in the fluoride-supplemented group were exposed to 30 mg/L sodium
      fluoride (NaF) in commercial drinking water containing 0.07 mg/L NaF throughout
      the gestation and lactation periods. After the lactation period, young animals
      (first generation; F1) were exposed to the same amount of NaF in drinking water
      for four months. At the end of the four-month experimental period, nine randomly
      chosen male rats (F1) were sacrificed and lung tissues were removed for
      histopathological and enzymatic lipid peroxidation examination. The second
      generation rats were obtained from the remaining rats by the same method. They
      were also treated similarly. At the end of the four-month experimental period,
      nine randomly-chosen male rats (F2) were sacrificed, and the lungs were removed
      for histological and lipid peroxidation examination. The rats in the control
      groups underwent the same procedure without NaF supplementation. It was found
      that the plasma fluoride and the lung TBARS levels of fluoride supplemented F1
      and F2 rats were higher than controls. There were marked histological changes in
      the lung tissues of fluoride supplemented F1 and F2 rats, as follows: in F1 rats;
      loss of alveolar architecture, emphysematous areas, descuamation of alveolar
      epithelium and alveolar congestion were observed. There were thickened
      interalveolar septae and congestion of alveolar septal vessels. Intraparenchymal
      thick-walled vessels were also observed. There were markedly perivascular and
      intraparenchymal focal mononuclear cell infiltrations. In F2 rats, in addition to
      these changes, there were lipid cell hyperplasia and increased connective tissue
      mass in the parenchymal areas. It is concluded that chronic fluorosis causes a
      marked destruction in lung tissues of F1 and F2 rats by causing lipid
      peroxidation.

PMID- 17533809
TI  - Evaluation of toxic metals in biological samples (scalp hair, blood and urine) of
      steel mill workers by electrothermal atomic absorption spectrometry.
AB  - The determination of toxic metals in the biological samples of human beings is an
      important clinical screening procedure. This study aimed to assess the possible
      influence of environmental exposure on production workers (PW) and quality
      control workers (QCW) of a steel mill, all male subjects aged 25-55 years. In
      this investigation, the concentrations of Pb, Cd, Ni and Cr were determined in
      biological samples (blood, urine and scalp hair samples) from these steel mill
      workers in relation to controlled unexposed healthy subjects of the same age
      group. After pre-treatment with nitric acid-hydrogen peroxide, the samples were
      digested via a microwave oven, and for comparison purposes, the same samples were
      digested by the conventional wet acid digestion method. The samples digested were
      subjected to graphite furnace atomic absorption spectrometry (GFAAS). To assess
      the reliability of these methods, critical factors, such as detection limit(s),
      calibration range(s), accuracy and precision, were studied. Quality control for
      these procedures was established with certified sample of human hair, urine and
      whole blood. The results indicate that the level of lead, cadmium and nickel in
      scalp hair, blood and urine samples were significantly higher in both groups of
      exposed workers (QW and PW) than those of the controls. The possible connection
      of these elements with the etiology of disease is discussed. The results also
      show the need for immediate improvements in workplace ventilation and industrial
      hygiene practices.

PMID- 17533810
TI  - Histopathological effects of organometallic maneb on testis in rats: a light and
      electron microscopic study.
AB  - Maneb is a dithiocarbamate fungicide that contains manganese. Dithiocarbamates
      are considered to be chemicals of low toxicity. An experimental group (n = 10)
      received maneb (obtained from Hoecht-Shering) at a concentration of 250 ppm in
      distilled water five days a week (treatment time is three weeks). It was orally
      administered by an orogastric tube. Acute oral LD 50 for male rats has been found
      to be 6750 mg/kg. The control group (n = 10) received distilled water. The whole
      body and testis weights of male rats were taken, and significant differences in
      body weight appeared between the control and treated groups (P < 0.01). No
      statistical difference was found in the testis weights between the control and
      treated groups (P < 0.05). Degeneration in spermatic cells can be seen in a few
      seminiferous tubules and vascularization. Transmission electron microscopy,
      interstitial cell and blood vessels of maneb-treated rat testis did not show any
      changes. Leydig cells with their large, excentric nuclei, cytoplasm with granular
      endoplasmic reticulum and other cell organelles appeared to be normal. Sertoli
      cells appeared unusually as a well developed rough endoplasmic reticulum and
      Golgi complexes had irregular compacted chromatin. Changes in Sertoli cell
      mitochondria included swelling and loss of cristae.

PMID- 17533811
TI  - The effect of tobacco consumption on blood cholinesterase levels among workers
      exposed to organophosphorus pesticides.
AB  - This is a cross-sectional study of workers in the pesticide industry, engaged in
      the formulation and packaging of organophosphorus compounds. A detailed history
      was taken of all study participants. Investigations carried out were the
      measurement of haemoglobin levels and estimation of whole blood cholinesterase
      levels. The prevalence of tobacco consumption in the industry is 76.09%. The mean
      age of employees was 42.8 years and the mean duration of service was 16.6 years.
      The study concludes that tobacco consumption increases the risk of toxicity due
      to organophosphorus pesticides, as indicated by a decrease in the blood
      cholinesterase levels. In this study, the age of employees and duration of
      service in the pesticide industry played no role in increasing the risk of toxic
      effects when exposed to organophosphorus pesticides.

PMID- 17533812
TI  - Clinical manifestations of lead workers of Mangalore, India.
AB  - OBJECTIVE: To correlate blood lead levels and clinical manifestations.
      PARTICIPANTS: Battery workers and painters (occupationally exposed to lead in and
      around Mangalore, India) and occupationally unexposed controls. MAIN OUTCOME
      MEASURES: We measured the blood lead levels by anodic stripping voltammetry, and
      a clinical examination was carried out on all participants. RESULTS: There was a
      statistically significant difference between the lead-exposed group and controls
      with respect to clinical manifestations. The prominent findings among the lead
      exposed group were fatigue, abdominal colic, abdominal discomfort, backache,
      muscular exhaustability, myalgia and paresthesia, at a blood lead level ranging
      from 0.4 to 116.6 microg/dL. CONCLUSIONS: Such a study on battery workers and
      painters has not been reported in India. Several attempts have been made over the
      years to relate blood lead levels to adverse health effects. It was not possible
      to determine a precise blood lead level below which symptoms never occur or a
      blood lead level at which symptoms are always reported.

PMID- 17533813
TI  - Ultrastructural effects of lead acetate on brain of rats.
AB  - Lead is a metal that has been implicated in toxic processes, which affect several
      organ systems in humans and other animals. The purpose of this study was to
      investigate the ultrastructural effects of lead on the brain of rats.Wistar
      Albino rats (180-200 g body weight) were divided into a controlled and lead
      acetate-exposed group. Rats received lead acetate at 500 ppm in their drinking
      water for 60 days. Both groups were fed with the same standard food, but lead
      acetate was added to the drinking water. During the experimental period, blood
      samples were drawn from the abdominal aorta of the anesthetised animals. At the
      end of exposure, body weight and blood lead levels were measured. The brain
      tissue samples were preapared and analysed by light and transmission electron
      microscopy. In the brain cortex, degeneration in some of the neuron cells, in the
      lumens of the blood vessels, dilation, hemorhagia and free floating erytrocytes
      were observed. Ultrastructural changes were revealed in the form of
      vacularisation of cell cytoplasm and degeneration in mitochondria, in the
      perinuclear cytoplasm, electron-dense inclusion bodies were detected, and
      dilation were in the endopasmic reticulum.

PMID- 17533814
TI  - ATSDR evaluation of the health effects of zinc and relevance to public health.
AB  - As part of its mandate, the Agency for Toxic Substances and Disease Registry
      (ATSDR) prepares toxicological profiles on hazardous chemicals found at
      Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA)
      National Priorities List (NPL) sites, which have the greatest public health
      impact. These profiles comprehensively summarise toxicological and environmental
      information. This article constitutes the release of portions of the
      Toxicological Profile for Zinc. The primary purpose of this article is to provide
      public health officials, physicians, toxicologists, and other interested
      individuals and groups with an overall perspective on the toxicology of zinc. It
      contains descriptions and evaluations of toxicological studies and
      epidemiological investigations, and provides conclusions, where possible, on the
      relevance of toxicity and toxicokinetic data to public health.

PMID- 17533815
TI  - Nitrogen isotopes.

PMID- 17533816
TI  - Fingerprinting perchlorate sources.

PMID- 17533817
TI  - E-waste creates hot spots for POPs.

PMID- 17533818
TI  - Losing the scent of danger.

PMID- 17533819
TI  - Lipid coating increases uptake of nanotubes.

PMID- 17533820
TI  - Microbes survive in soil in fullerenes.

PMID- 17533821
TI  - Spoonful of caution with nano hype. Interview by Naomi Lubick.

PMID- 17533822
TI  - Superfund and mining megasites.

PMID- 17533823
TI  - Monitoring the arsenic and iodine exposure of seaweed-eating North Ronaldsay
      sheep from the gestational and suckling periods to adulthood by using horns as a
      dietary archive.
AB  - Trace elements often accumulate in keratin-rich tissues. Hair, nails, and horns
      grow steadily but once formed are metabolically inactive and provide an archive
      of trace element exposure when analyzed in segments. Here we demonstrate the use
      of laser ablation ICP-MS for the high-resolution monitoring of trace elements in
      the horns of seaweed-eating sheep from North Ronaldsay, which live on grass only
      during lambing time. Due to this peculiar husbandry/dietary pattern and the fact
      that seaweed is rich in arsenic and iodine, we hoped to use iodine and arsenic as
      markers for seaweed ingestion. Cross sections and scans along the growing axis
      (representing the first 8-10 months of the sheep's life) revealed that these
      elements were not homogeneously distributed in the horn, with arsenic
      representing the amount of seaweed intake. The scans show the periods in which
      the lambs were fed on milk and grass and the change to seaweed ingestion with the
      successive replacement of milk with seaweed; this was supported by the carbon and
      nitrogen isotope signatures (delta13C and delta15N) of the horn and the arsenic
      speciation in the horn. The period of low arsenic accumulation in the horn had
      terrestrial isotope signatures and accumulated arsenic of mainly inorganic
      origin. The period of high arsenic accumulation was characterized by isotope
      signatures of marine origin, and the majority of accumulated arsenic in the horn
      was the main arsenosugar metabolite dimethylarsinic acid. Although we have
      investigated only four different horns of individual sheep, this study shows that
      arsenic is not significantly transported with milk. However, the high
      concentration of arsenic in the oldest part of the horn, which was formed in
      utero, points to a relatively high placental transport of arsenic while the ewe
      was eating seaweed. In contrast to arsenic, iodine is transported not only
      through milk ingestion but also through the placenta in large quantities.

PMID- 17533824
TI  - Polychlorinated naphthalenes in the Global Atmospheric Passive sampling (GAPS)
      study.
AB  - Air concentrations of polychlorinated naphthalenes (PCNs) were measured as part
      of the Global Atmospheric Passive Sampling (GAPS) study to assess their spatial
      distribution on a worldwide basis for the first sampling period between December
      2004 and March 2005. Results from more than 40 sites on seven continents show
      that PCNs are widespread, and highest levels are detected in urban/industrial
      locations consistent with other air sampling studies. The geometric mean air
      concentration of sigmaPCN is 1.6 pg/m3, ranging from below detection limit to 32
      pg/m3. With technical PCN mixtures largely no longer produced, combustion inputs
      may be contributing increasingly to contemporary PCN air burden globally.
      Enrichment of combustion-related congeners, e.g., PCN-52/60, -50, -51,-54, and 
      66/67, is observed in the congeneric compositions of air at nearly all sites
      compared to relatively minor contribution of these congeners in technical PCN
      formulations. Further evidence of current combustion sources influencing global
      PCN levels is a higher relative abundance of combustion-related congeners
      quantified by sigmaPCNcombustion/sigmaPCN. The relative contribution by
      combustion sources and emissions from technical PCN mixtures is expected to vary
      among sites since it depends on the combustion sources and the technical mixture
      used in a particular country or region.

PMID- 17533825
TI  - Hexachlorocyclohexanes in the Canadian archipelago. 1. Spatial distribution and
      pathways of alpha-, beta- and gamma-HCHS in surface water.
AB  - Hexachlorocyclohexanes (HCHs) in the surface water of the Canadian Archipelago
      and south Beaufort Sea were measured in summer, 1999. Overall concentrations of
      HCH isomers were in order of abundance: alpha-HCH (3.5 +/- 1.2 ng L(-1)) > gamma
      HCH (0.31 +/- 0.07 ng L(-1)) > beta-HCH (0.10 +/- 0.03 ng L(-1)). Concentrations
      and ratios of alpha-HCH/gamma-HCH decreased significantly (p < 0.001 to 0.003)
      from west to east, but there was no significant variation in alpha-HCH/ beta-HCH.
      The (+) enantiomer of alpha-HCH was preferentially degraded, with enantiomer
      fractions (EFs) ranging from 0.432-0.463 and increasing significantly (p < 0.001)
      from west to east. Concentrations also varied latitudinally for alpha-HCH and
      gamma-HCH (p < 0.002) but not for beta-HCH. Principal component analysis with
      variables alpha-HCH and gamma-HCH concentrations, EF, latitude, and longitude
      accounted for 71% (PC 1) and 16% (PC 2) of the variance. Mixing in the eastern
      Archipelago was modeled by assuming three end members with characteristic
      concentrations of alpha-HCH and gamma-HCH. The model accounted for the observed
      concentrations and higher EFs of alpha-HCH at the eastern stations.

PMID- 17533826
TI  - Identification of water-soluble heavy crude oil organic-acids, bases, and
      neutrals by electrospray ionization and field desorption ionization fourier
      transform ion cyclotron resonance mass spectrometry.
AB  - We identify water-soluble (23 degrees C) crude oil NSO nonvolatile acidic, basic,
      and neutral crude oil hydrocarbons by negative-ion ESI and continuous flow FD FT
      ICR MS at an average mass resolving power, m/deltam50% = 550,000. Of the 7000+
      singly charged acidic species identified in South American crude oil,
      surprisingly, many are water-soluble, and much more so in pure water than in
      seawater. The truncated m/z distributions for water-soluble components exhibit
      preferential molecular weight, size, and heteroatom class influences on
      hydrocarbon solubility. Acidic water-soluble heteroatomic classes detected at >1%
      relative abundance include O, O2, O3, O4, OS, O2S, O3S, O4S, NO2, NO3, and NO4.
      Parent oil class abundance does not directly relate to abundance in the water
      soluble fraction. Acidic oxygen-containing classes are most prevalent in the
      water-solubles, whereas acidic nitrogen-containing species are least soluble. In
      contrast to acidic nitrogen-containing heteroatomic classes, basic nitrogen
      classes are water-soluble. Water-soluble heteroatomic basic classes detected at
      >1% relative abundance include N, NO, NO2, NS, NS2, NOS, NO2S, N2, N2O, N2O2, OS,
      O2S, and O2S2.

PMID- 17533827
TI  - Time trends in sources and dechlorination pathways of dioxins in agrochemically
      contaminated sediments.
AB  - Although polychlorinated dibenzo-p-dioxins and dibezofurans (PCDD/Fs) are
      considered recalcitrant toward biotic and abiotic degradation processes,
      laboratory studies indicated lateral dechlorination pathways (removal of 2,3,7,8
      substituted chlorines) as possible natural remediation strategies under highly
      reducing conditions prevailing in contaminated sediments. Previous principal
      component analysis (PCA) of PCDD/Fs in Japanese sediments left unidentified a
      factor characterized by penta- to octa- homologues fully chlorinated at 1,2,6,9
      positions (1,2,6,9-pattern). In the present study, we reexamined PCDD/Fs in
      sediment cores from urban (Tokyo Bay) and remote (Lake Shinji) areas of Japan
      using positive matrix factorization (PMF) and revealed a lateral dechlorination
      fingerprint exhibiting the 1,2,6,9-pattern. Relative molar concentrations of
      putative lateral dechlorination products linearly increased with sediment depth,
      suggesting that decades of reaction resulted in the accumulation of hepta- and
      hexa- chlorinated lateral dechlorination products in the bottom sediment layers.
      Times required for in situ formation of dechlorination products were estimated to
      be at least 27.8 +/- 17.9 year(mole %)(-1) in Lake Shinji and 4.7 +/- 0.5
      year(mole %)(-1) in Tokyo Bay (both for the formation of 1,2,3,4,6,7,9-HpCDD) and
      are significantly longer than the dechlorination pathways observed in the
      laboratory.

PMID- 17533828
TI  - Characterizing and biological monitoring of polycyclic aromatic hydrocarbons in
      exposures to diesel exhaust.
AB  - Polycyclic aromatic hydrocarbons (PAHs) are one of the most important and
      carcinogenic components in diesel exhaust (DE). Therefore, ambient PAHs
      concentrations were measured and characterized for work areas in a locomotive
      engine inspection plant. Pre- and post-shift urine samples and concurrent air
      samples were collected on 17 workers to measure the concentration of urinary 1
      hydroxypyrene (1-OHP), a metabolite of pyrene. Increased urinary 1-OHP
      concentrations were observed over at least three consecutive sampling days. The
      biological kinetics of pyrene metabolism was studied with a one-compartment
      pharmokinetic model. The conversion rate and elimination rate of 1-OHP were
      estimated using nonlinear mixed-effects model, and validated with multiple
      nonlinear regression models by assessing the pattern of elimination rates of each
      worker separately. Urinary 1-OHP was confirmed to be a sensitive marker of PAHs
      exposure with mean half-life of 29 h in this population of Chinese workers. The
      study results would be beneficial to future occupational and environmental
      studies of PAH exposure.

PMID- 17533829
TI  - Micrometeorological measurements of methane and carbon dioxide fluxes at a
      municipal landfill.
AB  - Continuous and area-integrating monitoring of methane (CH4) and carbon dioxide
      (CO2) emissions was performed for 6 and 9 months, respectively, at a municipal
      landfill in Finland with the micrometeorological eddy covariance (EC) method. The
      mean CH4 emission from June to December was 0.53 mg m(-2) s(-1), while the CO2
      emission between February and December averaged 1.78 mg m(-2) s(-1). The CH4
      emissions from the summit area of the landfill, where active waste deposition was
      going on, were 1.7 times as high as from the slope area with a better surface
      cover. The variation in emissions over the source area of the measurement was
      high. Significant seasonal variation, linked to air and soil temperature, was
      only seen in the CO2 release rates. Results obtained with the EC method were
      comparable to those measured with closed static chambers. According to the EC
      measurements, the gas recovery system decreased CH4 fluxes by 69-79%. The ratio
      of the measured CH4 and CO2 emissions roughly indicated the route of the landfill
      gas emission, resembling the ratio of the gases measured in the gas wells (1.24)
      when the emission originated from the area with no oxidizing cover layer and
      being smaller when CH4 oxidation had taken place.

PMID- 17533830
TI  - Organochlorine compounds in trout from lakes over a 1600 meter elevation gradient
      in the Canadian Rocky Mountains.
AB  - The effect of altitude on the concentration and composition of organochlorine
      compounds (OC) in troutwas investigated along an elevation gradient of 1600 m in
      the Canadian Rocky Mountains. The eight lakes sampled were within or adjacent to
      national parks in sparsely settled parts of Alberta and British Columbia, thus
      contaminants were assumed to have derived from long-range atmospheric transport.
      Concentrations of several OCs in trout increased significantly with lake
      elevation. In general, these increases were most pronounced for the higher K(ow)
      pesticides (i.e., dieldrin and DDTs), and less pronounced for lower K(ow)
      pesticides (e.g., HCHs and HCB) and PCBs. Most OC concentrations in trout were
      inversely correlated with fish growth rate. Growth rate explained more of the
      variation for some OCs (particularly PCBs) than lake elevation. Differences in
      trophic position (indicated by delta15N) explained little of the variation in OC
      concentration in comparison to other factors such as lake elevation and the
      growth rate and age of trout. Using principal component analysis (PCA), we
      identified the importance of lake elevation and octanol/water partition
      coefficient (K(ow)) to the OC composition of trout.

PMID- 17533831
TI  - Spatial distribution of polybrominated diphenyl ethers and polychlorinated
      dibenzo-p-dioxins and dibenzofurans in soil and combusted residue at Guiyu, an
      electronic waste recycling site in southeast China.
AB  - Surface soils and combusted residue from a village located in southeast China,
      which has been intensely involved in the dismantling and "recycling" of computer
      parts (e-waste) for the past decade, were analyzed for polybrominated diphenyl
      ethers (PBDEs) and polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs).
      Total PBDE concentrations were highest in combusted residue of plastic chips and
      cables collected from a residential area (33,000-97,400 ng/g, dry wt), in soils
      from an acid leaching site (2720-4250 ng/g, dry wt), and a printer roller dump
      site (593-2890 ng/g, dry wt). BDE-209 was the most dominant congener (35-82%)
      among the study sites indicating the prevalence of commercial Deca-BDE, however
      signature congeners from commercial Penta- and Octa-BDE were also found. PCDD/F
      concentrations were also highest in soil from the acid leaching site (12,500
      89,800 pg/g, 203-1100 pg WHO-TEQ/g, dry wt) and in combusted residue (13,500
      25,300 pg/g, 84.3-174 pg WHO-TEQ/g, dry wt) and were comparable to PCDD/F levels
      of some open dumping sites in Asian developing countries. Of the e-waste
      activities, acid leaching and open burning emitted the highest concentrations of
      PBDEs and PCDD/Fs. This study is among the very few studies dealing with the
      important issue of pollution generated from crude e-waste recycling. Our results
      showthatthe crude processing of e-waste has become one of the major contributors
      of PBDEs and PCDD/Fs to the terrestrial environment.

PMID- 17533832
TI  - Including sorption to black carbon in modeling bioaccumulation of polycyclic
      aromatic hydrocarbons: uncertainty analysis and comparison to field data.
AB  - Model estimations of bioaccumulation of polycyclic aromatic hydrocarbons (PAHs)
      have been higher than field or laboratory data. This has been explained by strong
      sorption to black carbon (BC). In this paper, eight previously published
      bioaccumulation datasets were reinterpreted in terms of additional BC sorption.
      Biota--Solids Accumulation Factors (BSAFs) of PAHs typically decreased by 1-2
      orders of magnitude and were better in line with field data in marine, fresh
      water, and terrestrial ecosystems. Probabilistic BC-inclusive modeling showed
      that if BC content is not accurately known, uncertainty in BSAFs is 2-3 orders of
      magnitude (90 percentile confidence interval) due to uncertainty in the BC
      sorption term. When BC contents are measured, the deviation between model
      estimations and field measurements reduces to about a factor of 3. This implies
      that including routine measurements of BC contents is crucial in improving risk
      estimations of PAHs.

PMID- 17533833
TI  - Mercury speciation in piscivorous fish from mining-impacted reservoirs.
AB  - Guadalupe Reservoir (GUA), California, and Lahontan Reservoir (LAH), Nevada, U.S.
      are both affected either directly or indirectly by the legacy of gold and silver
      mining in the Sierra Nevada during the nineteenth century. Analysis of total
      mercury in fish from these lentic systems consistently indicate elevated
      concentrations (>1 microg x g(-1) wet weight; hereinafter, all concentrations are
      reported as wet weight unless indicated otherwise) well above the U.S.
      Environmenal Protection Agency's human consumption advisory level for fish (<0.3
      microg x g(-1)). Replicate X-ray absorption near edge structure (XANES) analyses
      on largemouth bass and hybrid striped bass from GUA and LAH were performed to
      determine predominant chemical species of mercury accumulated by these high
      trophic-level piscivores that are exposed to elevated mercury through trophic
      transfer in mining-impacted lentic systems. Despite distinct differences in
      mercury source, the proximity of the source, and concentrations of complexing
      ligands, results of XANES analysis clearly indicated that mercury accumulated in
      these individual fish from the two reservoirs were dominated by methylmercury
      cysteine complexes. These findings are consistent with results from commercial
      fish species inhabiting marine environments which are presumed to include
      differing mercury sources (e.g., atmospheric, hydrothermal, or benthic). The
      dominance of methylmercury cysteine complexes in muscle tissues of fish obtained
      from such contrasting environments and exposure conditions suggests that a
      generic toxicological model for the consumption of fish could be applicable over
      a wide range of ecologic settings.

PMID- 17533834
TI  - Biosorption of nonpolar hydrophobic organic compounds to Escherichia coli
      facilitated by metal and proton surface binding.
AB  - We observed that the presence of transition metal ion, Ag+, Cu2+, or Fe3+, at a
      concentration of 3 mg L(-1) increases sorption of two nonpolar hydrophobic
      organic compounds (HOCs), phenanthrene (PHEN), and 1,2,4,5-tetrachlorobenzene
      (TeCB) by 1.5-4 times to Gram-negative bacteria Escherichia coli. Complexation of
      transition metals with the deprotonated functional groups (mainly carboxyl) of
      bacterial cell walls neutralizes the negative charge, making the bacterial
      surface less hydrophilic and enhancing hydrophobic partition of HOCs. This is
      evidenced by the fact that the zeta potential (zeta) value of bacteria becomes
      less negative when a transition metal is present. Furthermore, the observed
      higher sorption of PHEN than TeCB at low pH (3.8) cannot be fully explained by
      the pH-dependent hydrophobic effects. The results led us to propose two specific
      sorption mechanisms for pi-donor compounds: cation-pi interactions with
      protonated amines and pi H-bonding with protonated carboxyls. The biosorption of
      PHEN was best described as pi-donor compared to the biosorption of TeCB
      considered non-pi-donor. Results of the present study highlight that the presence
      of coexisting transition metals and changes on pH have a major effect on the
      biosorption of nonpolar HOCs.

PMID- 17533835
TI  - Measurements of the volatility of aerosols from alpha-pinene ozonolysis.
AB  - The temperature-dependence of secondary organic aerosol (SOA) concentrations is
      measured using a temperature-controlled smog chamber. Aerosols are generated from
      reaction of alpha-pinene (14-150 ppb) and ozone at a constant temperature of 22
      +/- 2 degrees C in the presence of the OH-scavenger 2-butanol. After the
      reactions are completed the chamber is heated or cooled in a range from 20 to 40
      degrees C. SOA volume concentrations increase at temperatures below the initial
      formation temperature and decrease at elevated temperatures. The response to the
      temperature change as measured by percent mass change per degree ranged from -0.4
      to -3.6% K(-1), for a total mass reduction of 5-60% upon heating from 22 to 35
      degrees C. The reported range is due to two factors: (1) experimental
      uncertainty, arising mainly from uncertainty in evaporation and condensation
      behavior of particles lost to the chamber wall; (2) differences in the
      temperature response from experiment to experiment. Aerosol temperature
      sensitivity was also measured by tandem differential mobility analysis (TDMA)
      where similarly generated SOA were heated from 20 to 25 degrees C to 30-40
      degrees C with residence times of 0.5-1.5 min, resulting in particle volume
      reductions of up to 20%. The TDMA experiments indicate that evaporation of the
      SOA particles in this system occurs with a potentially significant mass transfer
      limitation (e.g., accommodation coefficient <0.1).

PMID- 17533836
TI  - Biological reduction of Np(V) and Np(V) citrate by metal-reducing bacteria.
AB  - Oxidized actinide species are often more mobile than reduced forms.
      Bioremediation strategies have been developed to exploit this chemistry and
      stabilize actinides in subsurface environments. We investigated the ability of
      metal-reducing bacteria Geobacter metallireducens and Shewanella oneidensis to
      enzymatically reduce Np(V) and Np(V) citrate, as well as the toxicity of Np(V) to
      these organisms. A toxic effect was observed for both bacteria at concentrations
      of > or = 4.0 mM Np(V) citrate. Below 2.0 mM Np(V) citrate, no toxic effect was
      observed and both Fe(III) and Np(V) were reduced. Cell suspensions of S.
      oneidensis were able to enzymatically reduce unchelated Np(V) to insoluble
      Np(IV)(s), but cell suspensions of G. metallireducens were unable to reduce
      Np(V). The addition of citrate enhanced the Np(V) reduction rate by S.
      oneidensisand enabled Np(V) reduction by G. metallireducens. The reduced form of
      neptunium remained soluble, presumably as a polycitrate complex. Growth was not
      observed for either organism when Np(V) or Np(V) citrate was provided as the sole
      terminal electron acceptor. Our results show that bacteria can enzymatically
      reduce Np(V) and Np(V) citrate, but that the immobilization of Np(IV) may be
      dependent on the abundance of complexing ligands.

PMID- 17533837
TI  - The effects of plants on the mobilization of Cu and Zn in soil columns.
AB  - Whereas metal effects on plants have been well studied, much less is known about
      plant effects on metal mobilization in soils. We investigated metal mobilization
      and speciation with a resolution of a few cm in soil columns planted with willows
      (Salix viminalis). In the presence of plants, the concentration profiles of
      dissolved organic carbon (DOC), major ions (e.g., Ca), Cu, and Zn exhibited more
      variation than in the absence of plants, and both smaller and larger
      concentrations were observed, indicative of strong local effects. The Cu
      concentration in the absence and presence of plants was controlled by DOC
      mobilization and could be described by the same relationship. Zn mobilization was
      controlled by DOC and Ca in the plant-free system and by pH and Ca in the
      presence of plants. Cu2+ and labile Zn were reasonably well predicted by the NICA
      Donnan model and were influenced by the plant-induced changes of the soil
      solution composition. Plant uptake reduced the dissolved Zn concentration and
      transpiration reduced Cu and Zn leaching.

PMID- 17533838
TI  - Examination of NOM chlorination reactions by conventional and stop-flow
      differential absorbance spectroscopy.
AB  - Mechanisms of chlorination of natural organic matter (NOM) in surface water (Lake
      Washington) were explored via differential spectroscopy. Two types of
      differential spectra (overall and incremental) were generated for this water
      chlorinated at pH 7 using varying chlorine doses and reaction times. The
      differential spectra contain two kinetically and spectroscopically distinct
      components. One of these components is attributable to functional groups that
      react rapidly with chlorine, while the other reflects transformations of slowly
      reacting chromophores that arise following the depletion of the fast
      chromophores. Small concentrations of disinfection byproducts (DBPs), exemplified
      in this study by dichloroacetic acid and chloral hydrate, were produced during
      the initial phase of chlorination, when the fast-reacting chromophores were being
      consumed. Rather, the release of those DBPs was correlated with the breakdown of
      the slowly reacting chromophores.

PMID- 17533839
TI  - Effects of dissolved carbonates and carboxylates on the sorption of thiuram
      disulfide pesticides on humic acids and model surfaces.
AB  - The sorption of a hydrophobic pesticide, thiram, on humic acid (HA) occurs via a
      specific pH-dependent binding of thiram at the deprotonated carboxylates of humic
      acid, forming a species thiram-[HACOO-] with K = 0.69. Similarly, thiram was
      sorbed by two model polycarboxylate-{SiO2COOH} materials via the formation of a
      surface species thiram-{SiO2COO-} with K = 0.45 between thiram and the
      eprotonated carboxylates grafted on SiO2 particles. In all cases, allowance of
      presence of bicarbonate at natural concentration caused severe inhibition of
      thiram's sorption. Oxalate and formate mimic the inhibitive effect of
      bicarbonate. Theoretical fit of the data showed that the inhibitive effect of
      HCO3- is due to the formation of the anionic species [thiram-HCO3](-1) (with K =
      0.90) which is water soluble and competes with the bound species thiram-{HACOO-}.
      The same phenomena were observed for the sorption of disulfiram. The specific
      interaction phenomena reported here bear relevance to the sorption properties of
      thiram and disulfiram on real soils and, therefore, may determine their
      environmental fate.

PMID- 17533840
TI  - Relative importance of solid-phase phosphorus and iron on the sorption behavior
      of sediments.
AB  - Of all the metal oxide particles, amorphous iron oxides have the greatest
      adsorption capacity for phosphate. Coastal sediments are often coated with
      terrigenous amorphous iron oxides, and those containing high iron are thought to
      have a high adsorption capacity. However, this conventional wisdom is based
      largely upon studies of phosphate adsorption on laboratory-synthesized minerals
      themselves containing no phosphorus. Using natural sediments that contain
      variable phosphorus and iron, our results demonstrate thatthe exchangeable
      phosphate rather than the iron oxides of sediments governs the overall sorption
      behavior. The iron oxide content becomes important only in sediments that are
      poor in phosphorus. A total of 40 sampling sites across the Florida Bay provide
      detailed spatial distributions both of the sediment's zero equilibrium phosphate
      concentration (EPC0) and of the distribution coefficient (Kd) that are consistent
      with the distribution of the exchangeable phosphate content of the sediment. This
      study provides the first quantitative relationships between sorption
      characteristics (EPC0 and Kd) and the exchangeable phosphate content of natural
      sediments.

PMID- 17533841
TI  - Oxygen and chlorine isotopic fractionation during perchlorate biodegradation:
      laboratory results and implications for forensics and natural attenuation
      studies.
AB  - Perchlorate is a widespread environmental contaminant having both anthropogenic
      and natural sources. Stable isotope ratios of O and Cl in a given sample of
      perchlorate may be used to distinguish its source(s). Isotopic ratios may also be
      useful for identifying the extent of biodegradation of perchlorate, which is
      critical for assessing natural attenuation of this contaminant in groundwater.
      For this approach to be useful, however, the kinetic isotopic fractionations of O
      and Cl during perchlorate biodegradation must first be determined as a function
      of environmental variables such as temperature and bacterial species. A
      laboratory study was performed in which the O and Cl isotope ratios of
      perchlorate were monitored as a function of degradation by two separate bacterial
      strains (Azospira suillum JPLRND and Dechlorospirillum sp. FBR2) at both 10
      degrees C and 22 degrees C with acetate as the electron donor. Perchlorate was
      completely reduced by both strains within 280 h at 22 degrees C and 615 h at 10
      degrees C. Measured values of isotopic fractionation factors were epsilon(18)O = 
      36.6 to -29.0% per hundred and epsilon(37)Cl = -14.5 to -11.5% per hundred, and
      these showed no apparent systematic variation with either temperature or
      bacterial strain. An experiment using (18)O-enriched water (delta(18)O = +198%
      per hundred) gave results indistinguishable from those observed in the
      isotopically normal water (delta(18)O = -8.1% per hundred) used in the other
      experiments, indicating negligible isotope exchange between perchlorate and water
      during biodegradation. The fractionation factor ratio epsilon(18)O/epsilon(37)Cl
      was nearly invariant in all experiments at 2.50 +/- 0.04. These data indicate
      that isotope ratio analysis will be useful for documenting perchlorate
      biodegradation in soils and groundwater. The establishment of a microbial
      fractionation factor ratio (epsilon(18)O/ epsilon(37)Cl) also has significant
      implications for forensic studies.

PMID- 17533842
TI  - Dicarbonyl products of the OH radical-initiated reactions of naphthalene and the
      Cl- and C2-alkylnaphthalenes.
AB  - Naphthalene and the C1- and C2-alkylnaphthalenes are the most abundant polycyclic
      aromatic hydrocarbons (PAHs) in urban atmospheres. Their major atmospheric loss
      process is by gas-phase reaction with hydroxyl (OH) radicals. In this study, we
      have used in situ direct air sampling atmospheric pressure ionization mass
      spectrometry (API-MS) as well as gas chromatography-mass spectrometry (GC/MS)
      techniques to investigate the products of the gas-phase reactions of OH radicals
      with naphthalene, naphthalene-ds, 1- and 2-methylnaphthalene (MN), 1- and 2-MN
      dio, 1- and 2-ethylnaphthalene (EN), and the 10 isomeric dimethylnaphthalenes
      (DMNs). The major reaction products are ring-opened dicarbonyls that are 32 mass
      units higher in molecular weight than the parent compound, one or more ring
      opened dicarbonyls of lower molecular weight resulting from loss of two P-carbons
      and associated alkyl groups, and ring-containing compounds that may be epoxides.
      Phthalic anhydride and alkyl-substituted phthalic anhydrides were observed as
      second generation products. The position of alkyl-substitution on the naphthalene
      ring is a key factor determining the ring cleavage site and the isomeric product
      distribution.

PMID- 17533843
TI  - Free zinc ion and dissolved orthophosphate effects on phytoplankton from Coeur
      d'Alene Lake, Idaho.
AB  - Coeur d'Alene Lake in northern Idaho is fed by two major rivers: the Coeur
      d'Alene River from the east and the St. Joe River from the south, with the
      Spokane River as its outlet to the north. This phosphorus-limited lake has been
      subjected to decades of mining (primarily for zinc and silver) and other
      anthropogenic inputs. A 32 full-factorial experimental design was used to examine
      the interactive effects of free (uncomplexed) zinc ion and dissolved
      orthophosphate concentrations on phytoplankton that were isolated from two sites
      along a longitudinal zinc-concentration gradient in Coeur d'Alene Lake. The two
      sites displayed different dominanttaxa. Chlorella minutissima, a dominant species
      near the southern St. Joe River inlet, exhibited greater sensitivity to free Zn
      ions than Asterionella formosa, collected nearer the Coeur d'Alene River mouth
      with elevated dissolved-zinc concentrations. Empirical phytoplankton-response
      models were generated to describe phytoplankton growth in response to remediation
      strategies in the surrounding watershed. If dissolved Zn can be reduced in the
      water column from >500 nM (i.e., current concentrations near and down stream of
      the Coeur d'Alene River plume) to <3 nM (i.e., concentrations near the southern
      St. Joe River inlet) such that the lake is truly phosphorus limited, management
      of phosphorus inputs by surrounding communities will ultimately determine the
      limnologic state of the lake.

PMID- 17533844
TI  - Quantifying PM2.5 source contributions for the San Joaquin Valley with
      multivariate receptor models.
AB  - UNMIX and Positive Matrix Factorization (PMF) solutions to the Chemical Mass
      Balance (CMB) equations were applied to chemically speciated PM2.5 measurements
      from 23 sites in California's San Joaquin Valley to estimate source
      contributions. Six and seven factors were determined by UNMIX for the low_PM2.5
      period (February to October) and high_PM2.5 period (November to January),
      respectively. PMF resolved eightfactors for each period that corresponded with
      the UNMIX factors in chemical profiles and time series. These factors are
      attributed to marine sea salt, fugitive dust, agriculture-dairy, cooking,
      secondary aerosol, motor vehicle, and residential wood combustion (RWC)
      emissions, with secondary aerosol and RWC accounting for over 70% of PM2.5 mass
      during the high_PM2.5 period. A zinc factor was only resolved by PMF. The
      contribution from motor vehicles was between 10 and 25% with higher percentages
      occurring in summer. The PMF model was further evaluated by examining (1) site
      specific residuals between the measured and calculated concentrations, (2)
      comparability of motor vehicle and RWC factors against source profiles obtained
      from recent emission tests, (3) edges in bi-plots of key indicator species, and
      (4) spatiotemporal variations of the factors' strengths. These evaluations
      support the compliance with model assumptions and give a higher confidence level
      to source apportionment results for the high_PM2.5 period.

PMID- 17533845
TI  - Estimating enthalpy of vaporization from vapor pressure using Trouton's rule.
AB  - The enthalpy of vaporization of liquids and subcooled liquids at 298 K (delta
      H(VAP)) is an important parameter in environmental fate assessments that consider
      spatial and temporal variability in environmental conditions. It has been shown
      that delta H(VAP)P for non-hydrogen-bonding substances can be estimated from
      vapor pressure at 298 K (P(L)) using an empirically derived linear relationship.
      Here, we demonstrate that the relationship between delta H(VAP)and PL is
      consistent with Trouton's rule and the ClausiusClapeyron equation under the
      assumption that delta H(VAP) is linearly dependent on temperature between 298 K
      and the boiling point temperature. Our interpretation based on Trouton's rule
      substantiates the empirical relationship between delta H(VAP) degree and P(L)
      degrees for non-hydrogen-bonding chemicals with subcooled liquid vapor pressures
      ranging over 15 orders of magnitude. We apply the relationship between delta
      H(VAP) degrees and P(L) degrees to evaluate data reported in literature reviews
      for several important classes of semivolatile environmental contaminants,
      including polycyclic aromatic hydrocarbons, chlorobenzenes, polychlorinated
      biphenyls and polychlorinated dibenzo-dioxins and -furans and illustrate the
      temperature dependence of results from a multimedia model presented as a
      partitioning map. The uncertainty associated with estimating delta H(VAP)degrees
      from P(L) degrees using this relationship is acceptable for most environmental
      fate modeling of non-hydrogen-bonding semivolatile organic chemicals.

PMID- 17533846
TI  - Screening and ranking of POPs for global half-life: QSAR approaches for
      prioritization based on molecular structure.
AB  - Persistence in the environment is an important criterion in prioritizing
      hazardous chemicals and in identifying new persistent organic pollutants (POPs).
      Degradation half-life in various compartments is among the more commonly used
      criteria for studying environmental persistence, but the limited availability of
      experimental data or reliable estimates is a serious problem. Available half-life
      data for degradation in air, water, sediment, and soil, for a set of 250 organic
      POP-type chemicals, were combined in a multivariate approach by principal
      component analysis to obtain a ranking of the studied organic pollutants
      according to their relative overall half-life. A global half-life index (GHLI)
      applicable for POP screening purposes is proposed. The reliability of this index
      was verified in comparison with multimedia model results. This global index was
      then modeled as a cumulative end-point using a QSAR approach based on few
      theoretical molecular descriptors, and a simple and robust regression model
      externally validated for its predictive ability was derived. The application of
      this model could allow a fast preliminary identification and prioritization of
      not yet known POPs, just from the knowledge of their molecular structure. This
      model can be applied a priori also in the chemical design of safer and
      alternative non-POP compounds.

PMID- 17533847
TI  - Relating atrazine degradation rate in soil to environmental conditions:
      implications for global fate modeling.
AB  - With the ready availability of georeferenced environmental data, regional and
      global chemical fate models have become increasingly spatially explicit. However,
      the description of how chemical fate properties such as degradation rate
      constants and partition coefficients depend on environmental conditions has not
      kept up with these developments. Consequently, model results are often subject to
      large uncertainty stemming from inherent variability in these properties. Here,
      we present an extensive meta-analysis of soil degradation of one exemplary
      compound, the herbicide atrazine. In the first part of the paper, we present the
      results of an in-depth statistical analysis of the dependence of atrazine
      degradation rate constants on various environmental factors. In the second part,
      the resulting estimation equation for atrazine degradation rate constants is
      implemented in CliMoChem, a model for the prediction of global chemical fate,
      which we supplemented with spatial information on various soil descriptors, such
      as temperature, sand and clay content, organic carbon content, and pH. Estimates
      of polar accumulation, an important indicator of global chemical fate, were then
      compared between this model setup and estimates obtained when the degradation
      rate constant is represented by a single value or as being dependent on
      temperature only. Results for the three rate estimation methods demonstrate that
      a spatially explicit description of the soil degradation process results in 4
      fold higher estimates of polar accumulation, while reducing uncertainty in the
      prediction of this endpoint by more than 40%.

PMID- 17533848
TI  - Implementing the decoupled direct method for sensitivity analysis in a
      particulate matter air quality model.
AB  - The decoupled direct method (DDM) is an efficient and accurate way of performing
      sensitivity analysis to model inputs. As the impact of atmospheric particulate
      matter (PM) on human health and visibility became evident, the need to extend the
      DDM to PM sensitivity has grown. In this work, the DDM is implemented in the
      three PM modules employed in the Comprehensive Air-quality Model with extensions
      (CAMx): ISORROPIA for inorganic gas/aerosol partitioning, SOAP for secondary
      organic gas/aerosol partitioning, and RADM-AQ for aqueous-phase chemistry. The PM
      modules are complex and the DDM implementation is discussed in detail. Stand
      alone tests are performed for each PM module in which first-order sensitivities
      computed bythe DDM are compared tothe traditional brute-force method (BFM). The
      DDM sensitivities are shown to be accurate and agree well with the BFM within the
      linear response range. The SOAP module showed nearly linear response for up to +/
      30% changes in concentration inputs. The RADM-AQ module showed moderately
      nonlinear response in some tests but first-order sensitivities accounted for most
      of the response for input changes up to +/-20%. ISORROPIA shows greater deviation
      from linear response than the other PM modules and the near-linear range can be
      as restricted as +/-10% changes in concentration inputs. Nonlinearity in
      ISORROPIA results both from the equations that describe thermodynamic equilibrium
      and the computational approaches within ISORROPIA that are employed to boost
      efficiency.

PMID- 17533849
TI  - Accounting for intrapopulation variability in biogeochemical models using agent
      based methods.
AB  - Present biogeochemical models typically use a lumped-system (population-level)
      modeling (LSM) approach that assumes average properties of a population within a
      control volume. For modern models that formulate phytoplankton growth as a
      nonlinear function of the internal nutrient (e.g., Droop kinetics), this
      averaging assumption can introduce a significant error. Agent-based (individual
      based) modeling (ABM) is an alternative approach that does not make the
      assumption of average properties. This paper presents a new agent-based
      phytoplankton model called iAlgae. The model is contrasted to a conventional
      lumped-system model, constructed based on identical underlying sub-models of
      nutrient uptake (including luxury uptake) and growth (cell quota, Droop model).
      The two models are validated against laboratory data and applied to a realistic
      scenario, consisting of a point source nutrient discharge into a river. For the
      realistic scenario, the ABM-predicted phytoplankton bloom is significantly lower
      than the LSM-predicted one, which is due to the intrapopulation distribution in
      cell quotas (due to different life histories of individuals) and nonlinearity of
      the growth rate model. In the ABM, a fraction of the population accumulates
      nutrients in excess of their immediate growth requirement (luxury uptake),
      leaving less for the remainder. Because the model is nonlinear, this results in a
      suboptimal (from a population perspective) utilization of nutrient and a lower
      population-level growth rate, compared to the case of no intrapopulation
      variability assumed by the LSM model. In general, the ABM and LSM approaches can
      produce significantly different results when incompletely mixed conditions lead
      to intrapopulation variability in cell properties (i.e., cell quota) and the
      model equations are nonlinear.

PMID- 17533850
TI  - Development of a house dust standard reference material for the determination of
      organic contaminants.
AB  - National-level health survey studies, such as the National Human Exposure
      Assessment Survey field program, have targeted the determination of organic
      contaminants in house dust in an effort to characterize human exposure in the
      domestic environment. As the effort to further understand human health effects in
      relation to organic contaminants associated with indoor dust accelerates, the
      need for an indoor dust Standard Reference Material (SRM) that is characterized
      for organic contaminants has become critical. To meet this need, a new organic
      contaminant house dust SRM has been developed. SRM 2585 Organic Contaminants in
      House Dust is intended for use in evaluating analytical methods for the
      determination of selected polycyclic aromatic hydrocarbons (PAHs),
      polychlorinated biphenyl (PCB) congeners, chlorinated pesticides, and
      polybrominated diphenyl ether (PBDE) congeners in house dust and similar
      matrices. The material may also be useful for evaluation and comparison of
      methods or instruments used for sampling in the indoor environment. Moreover,
      because of the material's extensive characterization (140 organic contaminant
      concentrations), the material may be useful in toxicity studies related to indoor
      air (in vitro or in vivo). The determination of the concentrations of PAHs
      (including alkyl-PAHs and PAHs with molecular mass 300 and 302), PCBs, and
      chlorinated pesticides is reported here, and these results are compared to values
      reported in the literature for house dust.

PMID- 17533851
TI  - Small-angle neutron scattering study of natural aquatic nanocolloids.
AB  - We examine the potential of small-angle neutron scattering (SANS) as a
      quantitative tool for studying nanostructure and length scales in natural
      freshwater aquatic colloidal dispersions (river water, river bed sediments,
      agricultural field drainage and slurry). Our results show that natural aquatic
      colloids are generally fractal with 3D network-type structures. None of these
      structures are consistent with diffusion-limited (DLCA) or reaction-limited
      (RLCA) particleparticle aggregation processes. The results also suggest three
      characteristic length scales: one ca. 3-10 nm, which we identify with "primary
      particle" sizes, another of ca. 20-50 nm suggestive of small aggregates, and the
      last ca. 50-200 nm which we postulate arises from transient networks of the
      aggregates. The role of organic matter in mediating colloid structure in aquatic
      dispersions was examined by neutron contrast variation and by measuring samples
      both before and after treatment with hydrogen peroxide. The results suggest that
      the aggregate network structure is mediated by organic matter.

PMID- 17533852
TI  - Near-infrared spectroscopy (NIRS) of epilithic material in streams has a
      potential for monitoring impact from mining.
AB  - There is an increasing demand for cost-effective methods for environmental
      monitoring, and here we assess the potential of near-infrared spectroscopy (NIRS)
      on epilithic material from streams (material covering submerged stones) as a new
      method for monitoring the impact of pollution from mining and mining-related
      industries. NIRS, a routine technique in industry, registers the chemical
      properties of organic material on a molecular level and can detect minute
      alterations in the composition of epilithic material. Epilithic samples from 65
      stream sites (42 uncontaminated and 23 contaminated) in northern Sweden were
      analyzed. The NIRS approach was evaluated by comparing it with the results of
      chemical analyses and diatom analyses of the same samples. Based on Principal
      Component Analysis, the NIRS data distinguished contaminated from uncontaminated
      sites and performed slightly betterthan chemical analyses and clearly betterthan
      diatom analyses. Of the streams designated a priori as contaminated, 74% were
      identified as contaminated by NIRS, 65% were identified by chemical analysis, and
      26% were identified by diatom analysis. Unlike chemical analyses of water
      samples, NIRS data reflect biological impacts in the streams, and the epilithic
      material integrates impact over time. Given that, and the simplicity of NIRS
      analyses, further studies to assess the use of NIRS of epilithic material as an
      inexpensive environmental monitoring method are justified.

PMID- 17533853
TI  - Methylene blue dye test for rapid qualitative detection of hydroxyl radicals
      formed in a Fenton's reaction aqueous solution.
AB  - A new procedure, the methylene blue dye test, qualitatively indicates the
      presence of hydroxyl radicals through the immediate, distinct bleaching of
      methylene blue dye on a paper test strip. This method employs a simple procedure
      requiring inexpensive materials, without the addition of competitive probe
      chemicals that potentially can interfere with the reaction. A Fenton's reaction
      with an Fe2+:H2O2 molar ratio of 1:20 generated hydroxyl radicals in Milli-Q
      water. The presence and absence of hydroxyl radicals were determined prior to and
      following quenching of the Fenton's reaction with 10% sodium sulfite,
      respectively. Bleaching of methylene blue dye, due to the presence of hydroxyl
      radicals in a sample,was indicated by a discoloration from a dark blue color to
      an almost white color, concentrated at the point of application, with a dark blue
      outline. A lack of bleaching indicated the absence of hydroxyl radicals in the
      sample. The presence of hydroxyl radicals was verified by benzoic acid chemical
      probe experiments with thin-layer chromatography (TLC) and spectrophotometric
      wavelength scans. The presence of hydroxyl radicals was indirectly determined by
      detection of hydroxylated benzoic acids on TLC plates and a violet solution color
      with a peak absorbance at a wavelength close to 520 nm.

PMID- 17533854
TI  - Development of a Luminex based competitive immunoassay for 2,4,6-trinitrotoluene
      (TNT).
AB  - Previously, a displacement immunoassay for 2,4,6-trinitrotoluene (TNT) was
      demonstrated using the Luminex 100. The work presented utilized this same
      specialized flow cytometer to demonstrate a highly sensitive and rapid
      competitive immunoassay for TNT. This required a TNT analog to be attached to the
      microsphere surface. Various linkers were evaluated; bovine serum albumin
      provided over 3 times more binding sites in comparison to various shorter diamine
      linkers. For this assay TNB-coated microspheres were added to samples; then
      biotinylated anti-TNT antibody and the reporter molecule, Streptavidin-R
      Phycoerythrin, were added. In the absence of TNT, a highly fluorescent complex
      was formed on the surface of the microsphere. The presence of TNT resulted in
      dose-dependent decreased fluorescence. Various anti-TNT antibodies were
      evaluated; Mab 30-1 gave the strongest response, yielding the lowest limit of
      detection (<1.0 ng/mL) and a dynamic range up to 1 microg/mL. Other factors such
      as reaction time, cross reactivity to other nitro-compounds, evaluation of
      acetone extracts of TNT contaminated soils, testing in environmental matrices
      such as fresh water and seawater were all completed. Finally, a multiplex assay
      for TNT and three protein toxins was successfully conducted using the competitive
      format.

PMID- 17533855
TI  - Simultaneous removal of SO2 and trace As2O3 from flue gas: mechanism, kinetics
      study, and effect of main gases on arsenic capture.
AB  - Sulfur dioxide (SO2) and trace elements are pollutants derived from coal
      combustion. This study focuses on the simultaneous removal of S02 and trace
      arsenic oxide (As2O3) from flue gas by calcium oxide (CaO) adsorption in the
      moderate temperature range. Experiments have been performed on a
      thermogravimetric analyzer (TGA). The interaction mechanism between As2O3 and CaO
      is studied via XRD detection. Calcium arsenate [Ca3(AsO4)2] is found to be the
      reaction product in the range of 600-1000 degrees C. The ability of CaO to absorb
      As2O3 increases with the increasing temperature over the range of 400-1000
      degrees C. Through kinetics analysis, it has been found that the rate constant of
      arsenate reaction is much higher than that of sulfate reaction. SO2 presence does
      not affect the trace arsenic capture either in the initial reaction stage when
      CaO conversion is relatively low or in the later stage when CaO conversion is
      very high. The product of sulfate reaction, CaS04, is proven to be able to absorb
      As2O3. The coexisting CO2 does not weaken the trace arsenic capture either.

PMID- 17533856
TI  - Development of engineered natural organic sorbents for environmental
      applications: 3. Reducing PAH mobility and bioavailability in contaminated soil
      and sediment systems.
AB  - The effects of engineered natural organic amendments on two measures of the
      environmental "availability" of polycyclic aromatic hydrocarbons (PAHs)
      associated with soil and sediment samples are assessed. Two soils spiked with
      pyrene alone and a sediment spiked with a mixture of 4 PAH compounds were amended
      with raw or superheated-water processed peat or soybean stalks, then aged for
      periods of either 62 or 105 days. The aged soils were then examined with respect
      to bioaccumulation of spiked pyrene by earthworms (Eisenia foetida), and to its
      human bioaccessibility as measured by extraction with simulated gastrointestinal
      fluid. Additions of processed amendments reduced both measures of availability by
      factors ranging from 7.6 to 27.0 for earthworm bioaccumulation and from 2.3 to
      8.8 for gastrointestinal extractability. All PAH compounds spiked to the sediment
      were reduced to varying extents in their availabilities to E. foetida and
      leachabilities by water by both processed and raw organic amendments.

PMID- 17533857
TI  - Photocatalytic degradation of two volatile fatty acids in an annular plug-flow
      reactor; kinetic modeling and contribution of mass transfer rate.
AB  - This study investigates the influence of inlet concentration and of flow rate on
      the degradation rate of two Volatile Fatty Acids (butyric and propionic acids).
      TiO2-coated nonwoven fiber textile was used as the photocatalyst in an annular
      plug-flow reactor at laminar flow regime. The kinetic follows a Langmuir
      Hinshelwood form. The oxidation rate increased with the flow rate, which
      emphasizes the influence of the mass transfer. A first design equation is
      proposed considering that the mass transfer could be neglected. Despite a good
      accuracy of the model, the determined kinetic constants are dependent on the flow
      rate which highlights the contribution of the mass transfer rate on the global
      degradation rate. Thus, a new design equation which includes the mass transfer
      rate was developed. Using this model, the degradation rate can be determined for
      any given flow rate. Moreover, it allows the estimation of the contribution of
      mass transfer and chemical reaction steps at given experimental conditions; and
      thus providing an interesting tool for reactor optimization or design.

PMID- 17533858
TI  - Electron and carbon balances in microbial fuel cells reveal temporary bacterial
      storage behavior during electricity generation.
AB  - Microbial fuel cells (MFCs) are emerging as a novel technology with a great
      potential to reduce the costs of wastewater treatment. Their most studied
      application is organic carbon removal. One of the parameters commonly used to
      quantify the performance of these cells is the Coulombic efficiency, i.e., the
      electron recovery as electricity from the removed substrate. However, the
      "inefficiencies" of the process have never been fully identified. This study
      presents a method that uses the combination of electrochemical monitoring,
      chemical analysis, and a titration and off-gas analysis (TOGA) sensor to identify
      and quantify the sources of electron loss. The method was used successfully to
      close electron, carbon, and proton balances in acetate and glucose fed microbial
      fuel cells. The method revealed that in the case that a substrate is loaded as
      pulses carbon is stored inside the cells during initial high substrate conditions
      and consumed during starvation, with up to 57% of the current being generated
      after depletion of the external carbon source. Nile blue staining of biomass
      samples revealed lipophilic inclusions during high substrate conditions, thus
      confirming the storage of polymeric material in the bacterial cells. The method
      also allows for indirect measurement of growth yields, which ranged from 0 to
      0.54 g biomass-C formed per g substrate-C used, depending on the type of
      substrate and the external resistance of the circuit.

PMID- 17533859
TI  - Surfactants differentially impact p,p'-DDE accumulation by plant and earthworm
      species.
AB  - The effect of four surfactants (Triton X-100, Tween-80, rhamnolipids,
      cyclodextrin) at 100-1000 mg/L on p,p'-DDE phytoextraction by Cucurbita pepo
      (zucchini) under field conditions and p,p'-DDE bioaccumulation by earthworm
      species (Eisenia fetida, Lumbricus terrestris) under laboratory conditions was
      investigated. Abiotically, surfactants (except cyclodextrin) increased
      contaminant desorption from soil by 4-fold, with higher concentrations generally
      promoting greater release. Cyclodextrin had no effect on DDE desorption. DDE
      concentrations in unamended zucchini roots and stems were 30- and 7.8-fold
      greater than soil levels, respectively, and 1.6% of the contaminant was extracted
      from the soil. The surfactant effects were cultivar specific. Triton X-100
      increased DDE uptake in "Costata" by 2.6-fold, yielding 5% contaminant
      phytoextraction. In "Goldrush", DDE accumulation decreased by 69% across all
      surfactants. Surfactants significantly increased DDE bioaccumulation by
      earthworms. For E. fetida with all surfactants and L. terrestriswith Triton X-100
      and cyclodextrin, DDE accumulation increased 2.5-7.2-fold, paralleling abiotic
      desorption. However, Tween-80 and rhamnolipids increased DDE accumulation in L.
      terrestris by 74 and 36 fold, respectively. These dramatic increases in
      contaminant bioaccumulation do not correlate with the increased availability
      observed abiotically. Surfactant-mediated increases in contaminant
      bioavailability are an unexpectedly complex process and clearly present
      unanticipated concerns over pollutant exposure to nontarget organisms.

PMID- 17533860
TI  - Phytochelatins and antioxidant systems respond differentially during arsenite and
      arsenate stress in Hydrilla verticillata (L.f.) Royle.
AB  - Serious contamination of aquatic systems by arsenic (As) in different parts of
      the world calls for the development of an in situ cost-effective phytoremediation
      technology. In the present investigation, plants of Hydrilla verticillata (L.f.)
      Royle were exposed to various concentrations of arsenate (As(V)) (0-250 microM)
      and arsenite (AsIII) (0-25 microM) and analyzed for accumulation responses vis-a
      vis biochemical changes. Total As accumulation was found to be higher in plants
      exposed to AsIII (315 microg g(-1) dw at 25 microM) compared to As(V) (205 microg
      g(-1) dw at 250 microM) after 7 d of treatment. Plants tolerated low
      concentrations of As(III) and As(V) by detoxifying the metalloid through
      augmented synthesis of thiols such as phytochelatins and through increased
      activity of antioxidant enzymes. While As(V) predominantly stimulated antioxidant
      enzyme activity, As(III) primarily caused enhanced levels of thiols. The maximum
      amount of As chelated by PCs was found to be about 39% in plants exposed to
      As(III) (at 10 microM) and 35% in As(V) exposed plants (at 50 microM) after 4 d.
      Only the respective highest concentrations of As(III) (25 microM) and As(V) (250
      microM) proved toxic for normal plant growth after prolonged treatment. Thus, H.
      verticillata forms a promising candidate for the phytoremediation of As
      contaminated water.

PMID- 17533861
TI  - A novel electro-fenton process for water treatment: reaction-controlled pH
      adjustment and performance assessment.
AB  - A novel electro-Fenton (E-Fenton) process was developed, in which the desired pH
      for an effective E-Fenton reaction and for a neutral treated media could be
      obtained by utilizing the reaction-released H+ and OH- in stead of chemical
      addition. In the laboratory-scale process using three chambers, the substrate
      solution pH > 4.0 was designed to be adjusted in situ through three sequencing
      steps: (I) pH reduction, (II) pH keeping for the effective E-Fenton reaction, and
      (III) pH recovery to neutral while the E-Fenton reaction continued. Experimental
      results demonstrated that such three-step pH adjustment was successfully achieved
      in this novel E-Fenton process, and that the pH adjustment was controlled by the
      E-Fenton reaction process. The performance of the novel process was assessed in
      terms of dimethyl phthalate (DMP) degradation in aqueous solution. The results
      revealed that the novel process was effective to reduce the DMP concentration and
      the total organic carbon (TOC) at steps II and III. Also, through experiments,
      the initial DMP solution pH > 4.0 was selected to be reduced to 3.5 in Step I of
      the process. This pH adjustment not only allowed the E-Fenton reaction to occur
      in its favorable pH range, but also benefited any potential subsequent biological
      treatment process or a final discharge. Moreover, the iron species could be
      recycled in the process.

PMID- 17533862
TI  - Sequential capture of CO2 and SO2 in a pressurized TGA simulating FBC conditions.
AB  - Four FBC-based processes were investigated as possible means of sequentially
      capturing SO2 and CO2. Sorbent performance is the key to their technical
      feasibility. Two sorbents (a limestone and a dolomite) were tested in a
      pressurized thermogravimetric analyzer (PTGA). The sorbent behaviors were
      explained based on complex interaction between carbonation, sulfation, and direct
      sulfation. The best option involved using limestone or dolomite as a SO2-sorbent
      in a FBC combustor following cyclic CO2 capture. Highly sintered limestone is a
      good sorbent for SO2 because of the generation of macropores during
      calcination/carbonation cycling.

PMID- 17533863
TI  - Vitrification of chromium electroplating sludge.
AB  - This work investigated the vitrification of hazardous electroplating sludge
      containing 140 mg/g Cr with/without bottom ash or cullet conditioning to lower
      specimens' basicities to 0.97-1.17 or 0.18-0.23, respectively. The conditioning
      was found to enhance the smooth/glassy appearance of slags but no ingot was
      obtained. Cr was >98% retained in the vitrified slags. Cr2O3 dominated in
      crystalline structure for the slag vitrified from the sludge, but this domination
      gradually shifted to Fe2SiO4/Fe3O4/SiO2 or SiO2 crystalline with increasing
      addition of bottom ash or cullet into the sludge, respectively. Compared to the
      raw sludge, the sludge-vitrified slag displayed lower leaching concentrations for
      most metals (particularly Cr (2.54 mg/L)), and smaller leaching ratios for Ag,
      Cr, and Cu (1.35, 0.02, and <0.01%, respectively) but greater ones for Cd, Pb,
      and Zn (3.83, 2.46, and 0.36%, respectively). The Cr leaching ratios were
      approximately 0.01% for the slags vitrified from the conditioned sludge.
      Independent of the slag basicity and crystalline structure, metal leaching
      quantity increased but leaching ratio decreased with increasing slag metal
      content. The slag compressive strengths were improved to >14.7 MPa at the mixing
      ratios > or = 2/1 and 1/1 for bottom ash/sludge and cullet/sludge, respectively.
      Fulfilling the criteria of Toxicity Characteristic Leaching Procedure (TCLP), all
      the slags were recyclable.

PMID- 17533864
TI  - Evaluation of volatile hydrocarbon emission characteristics of carbonaceous
      additives in green sand foundries.
AB  - This research studied a relative comparison of the hydrocarbon emissions during
      pyrolysis of four carbonaceous additives that can be used in green sand
      foundries. These included a highly volatile bituminous coal, anthracite, lignite,
      and cellulose. Analytic pyrolysis was conducted to simulate the heating
      conditions that the carbonaceous additives would experience during metal pouring.
      Specifically, the samples were flash pyrolyzed in a Curie-point pyrolyzer at 920
      degrees C with a heating rate of about 3000 degrees C/sec. This simulated some
      key features of the fast heating conditions that the carbonaceous additives would
      experience at the metal-mold interface when molten metal is poured into green
      sand molds. The samples were also pyrolyzed in a thermogravimetric analyzer (TGA)
      from ambient temperature to 1000 degrees C with a heating rate of 20 degrees
      C/min; and this simulated key features of the slow heating conditions that the
      carbonaceous additives would experience within the bulk of green sand molds that
      is further away from the metal-mold interface. Hydrocarbon emissions from flash
      pyrolysis were analyzed with GC-FID, while those from TGA pyrolysis were
      monitored with mass spectroscopy and GC-FID. The anthracite exhibited very low
      volatile hydrocarbons during both flash pyrolysis and TGA pyrolysis. The
      cellulose released less hydrocarbons than bituminous coal or lignite in TGA
      pyrolysis, but more hydrocarbons than those two during flash pyrolysis. This
      means that cellulose can release sufficient volatile hydrocarbons at the
      intensely heated molten metal-mold interface where they are most desired for
      ensuring casting quality, but much less within the bulk of the mold where they
      are undesirable. This characteristic of cellulose offers an important opportunity
      for green sand foundries to diminish their hazardous air pollutant (HAP)
      emissions.

PMID- 17533865
TI  - Transformation of polycyclic aromatic hydrocarbons by laccase is strongly
      enhanced by phenolic compounds present in soil.
AB  - Efficient transformation of several polycyclic aromatic hydrocarbons (PAHs) was
      obtained using a fungal laccase in the presence of phenolic compounds related to
      those formed in nature during the turnover of lignin and humus. The effect of
      these natural mediators, namely vanillin, acetovanillone, acetosyringone,
      syringaldehyde, 2,4,6-trimethylphenol, p-coumaric acid, ferulic acid, and sinapic
      acid, was compared with that of synthetic mediators such as 2,2'-azinobis-(3
      ethylbenzothiazoline-6-sulfonate) (ABTS) and 1-hydroxybenzotriazole (HBT).
      Anthracene was significantly degraded by laccase in the absence of mediators,
      whereas benzo[a]pyrene and pyrene were weakly transformed (less than 15% after 24
      h). Vanillin, acetovanillone, 2,4,6-trimethylphenol, and, above all, p-coumaric
      acid strongly promoted the removal of PAHs by laccase. 9,10-Anthraquinone was the
      main product detected from anthracene oxidation by all the laccase-mediator
      systems. The yield of anthraquinone formed was directly correlated with the
      amount of p-coumaric acid used. This compound resulted in a better laccase
      mediator than ABTS and close similarity to HBT, attaining 95% removal of
      anthracene and benzo[a]pyrene and around 50% of pyrene within 24 h.
      Benzo[a]pyrene 1,6-, 3,6-, and 6,12-quinones were produced during benzo[a]pyrene
      oxidation with laccase and p-coumaric acid, HBT, or ABTS as mediators, although
      use of the latter mediator gave further oxidation products that were not produced
      by the two other systems.

PMID- 17533866
TI  - Dredging associated effects: maternally transferred pollutants and DNA adducts in
      feral fish.
AB  - This study reports on the bioavailability, maternal transfer, and genotoxicity in
      feral fish of organic sediment pollutants. Northern pike (Esox lucius) and perch
      (Perca fluviatilis) were caught in a polluted bay before and during dredging
      activities and from reference areas. Polychlorinated biphenyls (PCBs) and
      polycyclic aromatic hydrocarbons (PAHs) were analyzed in ovulating eggs to
      investigate if the bay sediment posed a threat to early life-stages of fish. On
      the basis of previous investigations in this area, the level of exposure via
      maternal transfer and diffusive uptake of water-borne pollutants after hatch is
      likely sufficient to cause abnormalities in early life-stages of fish. During
      dredging, hepatic DNA adducts were elevated in adult fish, demonstrating an
      increased release of genotoxic compounds, which may contribute to adverse effects
      in aquatic organisms for several years. Although no substantial increase of
      maternally transferred pollutants were observed during dredging, this is the
      first time a correlation between hepatic DNA adducts in fish and pollutant burden
      in their eggs is demonstrated. Our findings underline the importance of combining
      chemical and toxicological methods as well as a need for greater emphasis on
      other polycyclic aromatic compounds in environmental risk evaluations.

PMID- 17533867
TI  - Effects of ambient NOx on chlorophyll a fluorescence in transplanted
      Flavoparmelia caperata (Lichen).
AB  - Transplants of Flavoparmelia caperata (L.) Hale were used to test possible
      relationships between chlorophyll a fluorescence (CaF) and ambient atmospheric
      conditions (temperature, precipitation, SO2 and NOx levels). Portions of the same
      thalli collected in a pristine site (A) of the Trieste Karst were exposed at that
      site, as the control, and in four other sites (B-E) in NE Italy, near to
      pollution monitoring stations. These sites had been selected in order to provide
      similar two by two climatic conditions (sites B,C: more humid; D,E: drier) and
      air pollution load (sites B,D: low; C,E: high). Before exposure and after 43 and
      90 days of exposure, CaF measurements were carried out in the laboratory under
      controlled conditions. A classification of meteorological and pollution
      parameters recorded during exposure substantially confirmed the differences
      between site couplets. After 90 days, samples from sites A (control) and B (with
      very low pollution load) showed only slightly reduced NPQ, qN, Fo, and Fm values.
      Samples from site D, with medium air pollution load, and sites C,E, with high air
      pollution loads, showed proportionally greater variation for most of the CaF
      parameters. A highly significant correlation was found between NPQ, qN, Fm, and
      NOx pollution but not with SO2 or O3. Effects of NOx on lichens and possible
      action mechanisms are discussed. The results strongly suggest that CaF
      measurements of lichen transplants can be a valid tool in biomonitoring studies.

PMID- 17533868
TI  - Impact of fullerene (C60) on a soil microbial community.
AB  - The nascent state of the nanoproduct industry calls for important early
      assessment of environmental impacts before significant releases have occurred.
      Clearly, the impact of manufactured nanomaterials on key soil processes must be
      addressed so that an unbiased discussion concerning the environmental
      consequences of nanotechnology can take place. In this study, soils were treated
      with either 1 microg C60 g(-1) soil in aqueous suspension (nC60) or 1000 microg
      C60 g(-1) soil in granularform, a control containing equivalent tetrahydrofuran
      residues as generated during nC60 formation process or water and incubated for up
      to 180 days. Treatment effects on soil respiration, both basal and glucose
      induced, were evaluated. The effects on the soil microbial community size was
      evaluated using total phospholipid derived phosphate. The impact on community
      structure was evaluated using both fatty acid profiles and following extraction
      of total genomic DNA, by DGGE after PCR amplification of total genomic DNA using
      bacterial variable V3 region targeted primers. In addition, treatment affects on
      soil enzymatic activities for beta-glucosidase, acid-phosphatase, dehydrogenase,
      and urease were followed. Our observations show that the introduction of
      fullerene, as either C60 or nC60, has little impact on the structure and function
      of the soil microbial community and microbial processes.

PMID- 17533869
TI  - Zinc toxicity to nitrification in soil and soilless culture can be predicted with
      the same biotic ligand model.
AB  - The inhibitory effect of Zn on the nitrification process in ZnCl2 spiked soils
      (12 soils, pH range 4.8-7.5) was compared to toxic effects of Zn on the
      nitrification by Nitrosospira sp. in soilless solutions with varying pH (pH 6-8)
      and ionic composition. The nitrification was reduced by 20% at Zn solution
      concentrations (EC20) ranging between 7 and 1200 microM Zn in the soil pore water
      and between 5 and 150 microM Zn in the soilless solutions. Protective effects of
      H+, Ca2+, and Mg2+ against Zn2+ toxicity were observed in both systems. Zinc
      speciation was determined, and 60-90% of the Zn in the soils and 35-80% of the Zn
      in the soilless solutions was present as Zn2+. A biotic ligand model and a
      Freundlich-type model, incorporating the competition of Zn2+ ions with H+, Ca2+,
      and Mg2+ for binding on the biotic ligands, were used to model the results. The
      Zn2+ activities resulting in 20% reduction of the nitrification were well
      predicted using the same parameters for both (soil and soilless) systems,
      indicating that microorganisms in soil are exposed to zinc through the free zinc
      ion in soil pore water.

PMID- 17533870
TI  - A sensory system at the interface between urban stormwater runoff and salmon
      survival.
AB  - Motor vehicles are a major source of toxic contaminants such as copper, a metal
      that originates from vehicle exhaust and brake pad wear. Copper and other
      pollutants are deposited on roads and other impervious surfaces and then
      transported to aquatic habitats via stormwater runoff. In the western United
      States, exposure to non-point source pollutants such as copper is an emerging
      concern for many populations of threatened and endangered Pacific salmon
      (Oncorhynchus spp.) that spawn and rear in coastal watersheds and estuaries. To
      address this concern, we used conventional neurophysiological recordings to
      investigate the impact of ecologically relevant copper exposures (0-20 microg/L
      for 3 h) on the olfactory system of juvenile coho salmon (O. kisutch). These
      recordings were combined with computer-assisted video analyses of behavior to
      evaluate the sensitivity and responsiveness of copper-exposed coho to a chemical
      predation cue (conspecific alarm pheromone). The sensory physiology and predator
      avoidance behaviors of juvenile coho were both significantly impaired by copper
      at concentrations as low as 2 microg/L. Therefore, copper-containing stormwater
      runoff from urban landscapes has the potential to cause chemosensory deprivation
      and increased predation mortality in exposed salmon.

PMID- 17533871
TI  - Common pattern of gene expression in response to hypoxia or cadmium in the gills
      of the European glass eel (Anguilla anguilla).
AB  - European eel (Anguilla anguilla) populations are in decline. Glass eel
      recruitment has fallen 10-fold since the early 1980s. Estuaries play a
      fundamental role in the life history of eels because glass eels must pass through
      them to reach freshwater ecosystems. Unfortunately, because of their geographical
      position at the upstream basin slopes, estuaries accumulate metals like cadmium
      and are important sites of hypoxia events. In this context, we studied the effect
      of the oxygen level on the ventilation of the glass eel. In parallel, glass eels
      were submitted to different dissolved cadmium concentrations (0, 2, and 10 microg
      L(-1)) under two oxygen levels (normoxia PO2 = 21 kPa and Hypoxia PO2 = 6 kPa).
      The expression level of various genes involved in the mitochondrial respiratory
      chain, in the cellular response to metal and oxidative stresses, was
      investigated. Our results showed that hypoxia enhances (1) ventilation of the
      postlarval stage and (2) Cd accumulation in gills only at the lowest metal water
      concentration tested (2 microg Cd L(-1)). At the gene level, Cd exposure mimics
      the effect of hypoxia since we observed a decrease in expression of genes
      involved in the respiratory chain and in the defense against oxidative stress.

PMID- 17533872
TI  - Visualizing the uptake of C60 to the cytoplasm and nucleus of human monocyte
      derived macrophage cells using energy-filtered transmission electron microscopy
      and electron tomography.
AB  - Concerns have been raised over the release of C60 nanoparticles into the
      environment and the potential risk to human health. To address these concerns it
      is essential to understand the pathways by which nanoparticles enter the cell,
      where they migrate to, and to establish whether the particles are transformed or
      modified within the cell. Imaging the subcellular distribution of carbon-based
      nanoparticles is particularly challenging. It is difficult to achieve high
      spatial resolution with sufficient image contrast to enable the nanoparticles to
      be identified within the cell. We have exposed human monocyte-derived macrophages
      (HMMs) to C60 and used energy filtered transmission electron microscopy (EFTEM)
      to image the distribution of C60 aggregates within intracellular compartments. We
      demonstrate that images recorded using low-loss electrons provide a significant
      improvement in contrast between the cellular material and the C60 allowing a
      clear differentiation between C60 and unstained cellular compartments and also
      between ordered and disordered forms of aggregated C60. We confirm that C60 is
      taken up by HMMs in vitro and is sequestered at several sites within the cell.
      These sites include the cytoplasm, lysosomes, and most significantly the cell
      nuclei.

PMID- 17533873
TI  - Simple and easy method to evaluate uptake potential of nanoparticles in mammalian
      cells using a flow cytometric light scatter analysis.
AB  - Many classes of nanoparticles have been synthesized and widely applied, however,
      there is a serious lack of information concerning their effects on human health
      and the environment. Considering that their use will increase, accurate and cost
      effective measurement techniques for characterizing "nanotoxicity" are required.
      One major toxicological concern is that nanoparticles are easily taken up in the
      human body. In this study, we developed a method of evaluating the uptake
      potential of nanosized particles using flow cytometric light scatter. Suspended
      titanium dioxide (TiO2) particles (5, 23, or 5000 nm) were added to Chinese
      hamster ovary cells. Observation by confocal laser scanning microscopy showed
      that the TiO2 particles easily moved to the cytoplasm of the cultured mammalian
      cells, not to the nucleus. The intensity of the side-scattered light revealed
      that the particles were taken up in the cells dose-, time-, and size-dependently.
      In addition, surface-coating of TiO2 particles changed the uptake into the cells,
      which was accurately reflected in the intensity of the side-scattered light. The
      uptake of other nanoparticles such as silver (Ag) and iron oxide (Fe3O4) also
      could be detected. This method could be used for the initial screening of the
      uptake potential of nanoparticles as an index of "nanotoxicity".

PMID- 17533874
TI  - In vivo biomodification of lipid-coated carbon nanotubes by Daphnia magna.
AB  - This study examined the interactions between Daphnia magna and a water-soluble,
      lysophophatidylcholine coated single-walled carbon nanotube. D. magna were able
      to ingest the nanotubes through normal feeding behavior and utilize the
      lysophophatidylcholine coating as a food source. D. magna were able to modify the
      solubility of the nanotube, likely through digestion of the lipid coating. This
      study provides evidence of biomodification of a carbon-based nanomaterial by an
      aquatic organism. The modification significantly altered the physical properties
      of the nanomaterial in freshwater. Acute toxicity was observed only in the
      highest test concentrations. These are important findings related to determining
      the behavior and potential toxicity of coated nanomaterials released into the
      environment.

PMID- 17533875
TI  - Diversion of attention in everyday concept learning: identification in the
      service of use.
AB  - Many people tend to believe that natural categories have perfectly predictive
      defining features. They do not easily accept the family resemblance view that the
      features characteristic of a category are not individually sufficient to predict
      the category. However, common category-learning tasks do not produce this simpler
      than-it-is belief. If there is no simple classification principle in a task, the
      participants know that fact and can report it. We argue that most category
      learning tasks in which family resemblance categories are used fail to produce
      the everyday simpler-than-it-is belief because they encourage analysis of
      identification criteria during training. To simulate the learning occurring in
      many natural circumstances, we developed a procedure in which participants'
      analytic activity is diverted from the way in which the stimuli are identified to
      the use to which the stimuli will be put. Finally, we discuss the prevalence of
      this diverted analysis in everyday categorization.

PMID- 17533876
TI  - Graded motor responses in the time course of categorizing atypical exemplars.
AB  - The time course of categorization was investigated in four experiments, which
      revealed graded competitive effects in a categorization task. Participants
      clicked one of two categories (e.g., mammal or fish) in response to atypical or
      typical exemplars (e.g., whale or cat) in the form of words (Experiments 1 and 2)
      or pictures (Experiments 3 and 4). Streaming x, y coordinates of mouse movement
      trajectories were recorded. Normalized mean trajectories revealed a graded
      competitive process: Atypical exemplars produced trajectories with greater
      curvature toward the competing category than did typical exemplars. The
      experiments contribute to recent examination of the time course of categorization
      and carry implications for theories of representation in cognitive science.

PMID- 17533877
TI  - The relationship of analogical distance to analogical function and preinventive
      structure: the case of engineering design.
AB  - Analogy was studied in real-world engineering design, using the in vivo method.
      Analogizing was found to occur frequently, entailing a roughly equal amount of
      within- and between-domain analogies. In partial support for theories of
      unconscious plagiarism (Brown & Murphy, 1989; Marsh, Landau, & Hicks, 1996) and
      Ward's (1994) path-of-least-resistance model, it was found that the reference to
      exemplars (in the form of prototypes) significantly reduced the number of between
      domain analogies between source and target, as compared with using sketches or no
      external representational systems. Analogy served three functions in relation to
      novel design concepts: identifying problems, solving problems, and explaining
      concepts. Problem identifying analogies were mainly within domain, explanatory
      analogies were mainly between domain, and problem-solving analogies were a
      mixture of within- and between-domain analogies.

PMID- 17533878
TI  - Nonintentional analogical inference in text comprehension.
AB  - We present findings suggesting that analogical inference processes can play a
      role in fluent comprehension and interpretation. Participants were found to use
      information from a prior relationally similar example in understanding the
      content of a later example, but they reported that they were not aware of having
      done so. These inference processes were sensitive to structural mappings between
      the two instances, ruling out explanations based solely on more general kinds of
      activation, such as priming. Reading speed measures were consistent with the
      possibility that these inferences had taken place during encoding of the target
      rather than during the later recognition test. These findings suggest that
      analogical mapping, though often viewed as an explicit deliberative process, can
      sometimes operate without intent or even awareness.

PMID- 17533879
TI  - Sample size and the detection of means: a signal detection account.
AB  - Using statistical theory as a basis, Kareev (e.g., 1995) claimed that people's
      ability to correctly infer the existence of a population correlation should be
      greater for small than for large samples. Simulations by R. B. Anderson, Doherty,
      Berg, and Friedrich (2005) identified conditions favoring small samples but could
      not determine whether such an advantage was due to sampling skew, variance, or
      central tendency displacement. In the present study, we investigated theoretical
      effects of sample size (n) on the detection of population means under
      circumstances in which sampling variance is unconfounded with skew or central
      tendency displacement. The results demonstrate an extremely limited, criterion
      specific, small-sample advantage that was attributable to n-related sampling
      variance and that occurred only with highly conservative, suboptimal criterion
      placement.

PMID- 17533880
TI  - The effects of social pressure on false memories.
AB  - The present experiments were designed to examine the effects of social pressure
      on false memories. Participants studied lists created to elicit false memories
      and then worked in conjunction with virtual confederates on a recognition memory
      task. In Experiment 1, participants worked with one or two confederates to
      complete multiple study-test trials. On the group tests, participants were
      implicitly pressured to recognize words that did not appear on the studied lists.
      Experiment 2 was implemented similarly, but utilized a presumably more difficult
      recognition test involving one long study phase followed by one long test phase.
      After the purported group tests in both experiments, participants completed
      surprise individual recognition tests. In both experiments, social pressure
      influenced participants' responses on group recognition tests and subsequent
      individual recognition tests. Furthermore, the results indicated that social
      pressure affected both veridical memories and false memories.

PMID- 17533881
TI  - The role of reminding in long-term memory for temporal order.
AB  - Order codes are one of the three main types of information that have been
      hypothesized to underlie memory for the times of life events. Published evidence
      for the theory, however, has come exclusively from research in which brief
      retention intervals have been used. In the first of two studies, 101 adults
      judged the order of pairs of movies released 5-14 years ago, half of which shared
      a common major actor. There was no evidence that related films could be ordered
      more accurately than unrelated ones. In the second study, 88 students were
      presented with in-class announcements that were either related or unrelated to an
      earlier announcement. Three weeks later,they judged the order of the pairs of
      announcements. There was no difference between the accuracy for the related and
      the unrelated pairs. The findings do not support the proposal that the automatic
      creation of order information at the time of encoding contributes to
      autobiographical memory.

PMID- 17533882
TI  - Linguistic focus and memory: an eye movement study.
AB  - We report an eyetracking study investigating the effects of linguistic focus on
      eye movements and memory during two readings of a text. Across two presentations
      of the text, a critical word either changed to a semantically related word or
      remained unchanged. Focus on the critical word was manipulated using context. Eye
      movements were monitored during reading, and there was a secondary task of
      detecting the word change. Results indicated that when a word changed,
      participants were more successful at detecting it when it was in focus. In the
      second display, there were more fixations and longer viewing times on a changed
      than on an unchanged word, but only when the critical word was in focus; eye
      movement data for changed and unchanged words did not differ when the word was
      not in focus. We suggest that linguistic focus leads to more detailed lexical
      semantic representations but not more effortful initial encoding of information.

PMID- 17533883
TI  - Metaphor and readers' attributions of intimacy.
AB  - Previous theorists have suggested that figurative language may be an especially
      salient means by which speakers and addressees establish and recognize specific
      feelings of interpersonal closeness. To explore readers' sensitivity to this
      interpersonal function of figurative language use, brief stories were created
      that described interactions between two ambiguously related characters. In the
      course of these conversational narratives, one character always used either a
      metaphoric or literal referring expression to refer to some antecedent
      information from the story. Across three experiments, readers consistently judged
      these story characters as knowing each other better when their interactions
      contained metaphoric references. Moreover, this occurred even when addressees
      failed to give explicit evidence of having understood the critical expressions.
      To the extent that language use highlights assumptions about commonalities,
      readers may generate inferences about social relationships alongside more meaning
      driven comprehension processes.

PMID- 17533884
TI  - On the nature of the affective priming effect: effects of stimulus onset
      asynchrony and congruency proportion in naming and evaluative categorization.
AB  - In line with the hypothesis that affective priming of evaluative categorization
      responses is based on processes that operate at a response selection stage, it
      has been observed that increasing the proportion of congruent trials brings about
      increased affective priming effects at short stimulus onset asynchronies (SOAs)
      in the evaluative categorization task. In the present study, we orthogonally
      manipulated the congruency proportion (.25, .50, and .75) and the SOA (0, 200,
      and 1,000 msec) in the evaluative categorization task and a naming task. Results
      showed that at both short and long SOAs, the affective priming effect in the
      evaluative categorization task was influenced by the congruency proportion. In
      contrast, affective priming effects in the naming task were unaffected by the
      congruency proportion at short SOAs. This pattern of results provides
      corroborating evidence for the hypotheses (1) that different processes underlie
      the affective priming effect in the evaluative categorization task and the naming
      task and (2) that valenced stimuli can automatically preactivate the memory
      representations of other, affectively related stimuli.

PMID- 17533885
TI  - Familiarity from orthographic information: extensions of the recognition without
      identification effect.
AB  - Two experiments were conducted to investigate the effect of letter location
      information in recognition memory judgments. The experiments used the recognition
      without identification paradigm (Peynircioglu, 1990), in which participants first
      attempt to identify the test item and then make a recognition decision as to
      whether or not the item was studied. In these studies, items that are not
      identified but that correspond to items that were presented are typically still
      rated as more likely to have been studied than those that were not presented. The
      present experiments demonstrated this finding with a variant of the conjunction
      lure paradigm. In Experiments 1 and 2, participants were tested with word
      fragments that were made from the letters of two words. When the letters were
      from studied items, fragments were rated higher than when the test items were
      derived from two unstudied items, or one studied item and one unstudied item,
      suggesting that recognition without identification is prone to the same types of
      errors as recognition with identification. Results are discussed in terms of
      familiarity effects in recognition memory.

PMID- 17533886
TI  - Reversing the picture superiority effect: a speed-accuracy trade-off study of
      recognition memory.
AB  - Speed-accuracy trade-off methods have been used to contrast single- and dual
      process accounts of recognition memory. With these procedures, subjects are
      presented with individual test items and required to make recognition decisions
      under various time constraints. In three experiments, we presented words and
      pictures to be intentionally learned; test stimuli were always visually presented
      words. At test, we manipulated the interval between the presentation of each test
      stimulus and that of a response signal, thus controlling the amount of time
      available to retrieve target information. The standard picture superiority effect
      was significant in long response deadline conditions (i.e., > or = 2,000 msec).
      Conversely, a significant reverse picture superiority effect emerged at short
      response-signal deadlines (< 200 msec). The results are congruent with views
      suggesting that both fast familiarity and slower recollection processes
      contribute to recognition memory. Alternative accounts are also discussed.

PMID- 17533887
TI  - Using prior knowledge to minimize interference when learning large amounts of
      information.
AB  - In three experiments, we examined mediated learning in situations involving
      learning a large amount of information. Participants learned 144 "facts" during a
      learning phase and were tested on facts during a test phase. In Experiments 1 and
      2, participants learned facts about familiar individuals, unfamiliar individuals,
      or unfamiliar individuals associated with familiar individuals. Prior knowledge
      reduced interference, even when it played only a mediating role. In Experiment 3,
      participants learned facts about unfamiliar individuals or unfamiliar countries,
      with half the participants in each group associating the unfamiliar items with
      familiar individuals. Again, use of prior knowledge to mediate learning reduced
      interference even when the new information was conceptually dissimilar to the
      previously known information. These results are consistent with the mental model
      account of long-term memory.

PMID- 17533888
TI  - Automatic activation of task-related representations in task shifting.
AB  - Stimulus displays consisting of a target and a distractor can produce task
      conflicts when target and distractor are associated with different tasks. The
      present study examined whether these stimulus-induced task conflicts are affected
      by priming the irrelevant task or by increasing the salience of the distractor.
      In a series of three experiments, we employed a task-shifting paradigm in which
      subjects had to apply one of two judgments to either the global or the local
      level of a hierarchical stimulus. In each block, the target level and the
      judgment were either constant or mixed. Stimulus-induced judgment conflicts were
      measured by comparing performance for stimuli associated with two judgments and
      stimuli associated with only one. It turned out that only mixing the target level
      and not mixing the judgment increased the conflicts. These findings indicate that
      only the salience of the distractor modulates stimulus-induced conflicts.

PMID- 17533889
TI  - Irrelevant speech effects and sequence learning.
AB  - The irrelevant speech effect is the finding that performance on serial recall
      tasks is impaired by the presence of irrelevant background speech. According to
      the object-oriented episodic record (O-OER) model, this impairment is due to a
      conflict of order information from two different sources: the seriation of the
      irrelevant speech and the rehearsal of the order of the to-be-remembered items.
      We tested the model's prediction that irrelevant speech should impair performance
      on other tasks that involve seriation. Experiments 1 and 2 verified that both an
      irrelevant speech effect and a changing state effect would obtain in a between
      subjects design in which a standard serial recall measure was used, allowing
      employment of a between-subjects design in subsequent experiments. Experiment 3
      showed that performance on a sequence-learning task was impaired by the presence
      of irrelevant speech, and Experiment 4 verified that performance is worse when
      the irrelevant speech changes more (the changing state effect). These findings
      support the prediction made by the O-OER model that one essential component to
      the irrelevant speech effect is serial order information.

PMID- 17533890
TI  - The spread of the phonological neighborhood influences spoken word recognition.
AB  - In three experiments, the processing of words that had the same overall number of
      neighbors but varied in the spread of the neighborhood (i.e., the number of
      individual phonemes that could be changed to form real words) was examined. In an
      auditory lexical decision task, a naming task, and a same-different task, words
      in which changes at only two phoneme positions formed neighbors were responded to
      more quickly than words in which changes at all three phoneme positions formed
      neighbors. Additional analyses ruled out an account based on the computationally
      derived uniqueness points of the words. Although previous studies (e.g., Luce &
      Pisoni, 1998) have shown that the number of phonological neighbors influences
      spoken word recognition, the present results show that the nature of the
      relationship of the neighbors to the target word--as measured by the spread of
      the neighborhood--also influences spoken word recognition. The implications of
      this result for models of spoken word recognition are discussed.

PMID- 17533891
TI  - Serial position effects in short-term visual memory: a SIMPLE explanation?
AB  - A version of Sternberg's (1966) short-term visual memory recognition paradigm
      with pictures of unfamiliar faces as stimuli was used in three experiments to
      assess the applicability of the distinctiveness-based SIMPLE model proposed by
      Brown, Neath, and Chater (2002). Initial simulations indicated that the amount of
      recency predicted increased as the parameter measuring the psychological
      distinctiveness of the stimulus material (c) increased and that the amount of
      primacy was dependent on the extent of proactive interference from previously
      presented stimuli. The data from Experiment 1, in which memory lists of four and
      five faces varying in visual similarity were used, confirmed the predicted
      extended recency effect. However, changes in visual similarity were not found to
      produce changes in c. In Experiments 2 and 3, the conditions that influence the
      magnitude of c were explored. These revealed that both the familiarity of the
      stimulus class before testing and changes in familiarity, due to perceptual
      learning, influenced distinctiveness, as indexed by the parameter c. Overall, the
      empirical data from all three experiments were well fit by SIMPLE.

PMID- 17533892
TI  - The mnemonic effects of recall on immediate retention.
AB  - In three experiments, we investigated the mnemonic effects of an initial recall
      on later recall in an immediate memory setting. Recall is generally assumed to
      interfere with the recall of subsequent items (output interference), but previous
      experiments have failed to control for the confounding effects of time. In the
      experiments reported here, the passage of time was held constant on all trials;
      what varied was whether an additional item was recalled (or simply presented)
      during the retention interval. The results revealed clear evidence of recall's
      mnemonic effects, but output interference seemed strongest when the initial
      recall was of an item that followed the target item in the memory list. When
      participants initially recalled an item immediately preceding the target, target
      recall improved. This pattern of results places constraints on current models of
      immediate retention.

PMID- 17533893
TI  - [Virgin olive oil. From legend to scientific knowledge of the nutraceutical
      aspects].
AB  - Proper nutrition has been considered the basis of good health since ancient
      times. Hippocrates (460-377 BC), father of modern medicine in the western world,
      claimed that "good health implies an awareness of the powers of natural or
      processed foods", the Salernitan School (eleventh-twelfth centuries) maintained
      that "the doctor must observe what food consists of, how much, and when it must
      be eaten", while Leonardo da Vinci (1452-1519) believed that "a man's life
      depends on what he eats". We know that lipids are important in nutrition and
      extra-virgin olive oil plays a predominant role in this field, recognised for its
      high levels of monounsaturated fatty acids. An example of a "nutraceutic" or
      "functional" food right from infancy, it is one of the best medicaments for
      delaying aging, and is also a good source of phytochemicals including
      polyphenolic compounds, squalene, alpha-tocopherol, carotenoid that may
      contribute to its overall therapeutic characteristics. An integral ingredient of
      the Mediterranean diet, extra-virgin olive oil has always been considered a
      middle road between food and medicine and there is growing evidence that its
      health benefits include reduction of coronary heart disease risk factor,
      prevention of several types of cancer, and the modification of immune and
      inflammatory responses. The origins of the olive tree date back to the
      Eneolithical era, or Copper Age, in the sixth millennium BC. Having first
      appeared in Italy during the Bronze Age, the fruit and oil of the olive tree were
      widely used in nutrition, medicine, art, literature, and daily life during the
      Etruscan and Roman civilisations, and throughout the Middle Ages and Renaissance.
      Mysteriously entwined with our own history, the olive tree has a human shape,
      strong, resilient, tenacious, filled with fruit, but also wounded, suffering and
      moving. Well-grounded reasons exist for considering olive oil the best
      nutritional gift we can offer ourselves as it preserves good health, improves the
      quality of our life and also makes it more enjoyable.

PMID- 17533894
TI  - [Italian guidelines and recommendations for prevention and treatment of pain in
      the newborn].
AB  - OBJECTIVE: Despite accumulating evidence that procedural pain experienced by
      preterm infants may have acute detrimental and even long-term effects on an
      infant's subsequent behavior and neurological outcome, neonates admitted to
      Neonatal Intensive Care Units still frequently experience acute and prolonged
      uncontrolled pain. Many invasive and surgical procedures are routinely performed
      at the bedside in the NICU without adequate pain management. AIM: To develop
      evidence-based guidelines and recommendations for pain control and prevention in
      Italian i.e. heel lancing, venipuncture and percutaneous venous line positioning,
      tracheal intubation, mechanical ventilation, lumbar puncture, chest tube
      positioning, for certain surgical procedures performed at the NICU, e.g. central
      venous cutdown, surgical PDA ligation, and cryotherapy, laser therapy for ROP,
      and for postoperative pain management. CONCLUSION: Adequate pain prevention and
      management should be an essential part of standard health care at the NICU, and
      recognizing and assessing sources of pain should be routine in the day-to-day
      practice of physicians and nurses taking care of the newborn. We hope these
      guidelines will contribute towards increasing the NICU caregiver's awareness and
      understanding of the importance of adequate pain control and prevention.

PMID- 17533895
TI  - [Activity of pediatric acceptance in the Polyclinic of Modena: 1999 to 2003].
AB  - The activity of the pediatric emergency ward in 1999-2003 period is described. An
      increasing number of contacts was recorded. Most of them should be considered
      improper. An extra health-care information is required, specially directed to the
      foreign families, who recently settled in our town. A pediatric outpatient clinic
      for non-critical patient could cover Sundays and holidays, as in other italian
      centers.

PMID- 17533896
TI  - [The short-stay observation unit: an experience of the Pediatric Department in
      Modena].
AB  - The use of a short-stay observation unit (OBI) in a pediatric department has
      reduced the number of admissions. Significant cost savings and a better care for
      children and their families have been also achieved. During the year 2003 in our
      department 1759 children received OBI. 226 (12.8%) were then admitted. 1553
      (87.2%) were discharged after a nine-hour mean stay. Descriptive statistics are
      used to outline the sample of patients and used treatments.

PMID- 17533898
TI  - [Congenital cystic adenomatoid malformation: a case report].
AB  - Cystic adenomatoid malformation is a rare pulmonary hamartomatous lesion, of an
      unknown etiology. Report a singular case of CAM of one newborn, with marked
      respiratory distress. Using different method (chest X-ray, Multidetector row CT
      associated at multiplanar and three-dimensional reconstructions), we obtained an
      accurate diagnosis of site and nature, critical for a correct therapeutic
      approach.

PMID- 17533897
TI  - [Cytomegalovirus-induced protein-losing gastropathy: a case report].
AB  - Protein-losing gastropathy is an uncommon disease of uncertain etiology, known
      also as Menetrier's disease. In medical literature only 50 pediatric cases have
      been described. These childhood forms, in contrast to classic adult Menetrier's
      disease, have a typical benign and transient course, and require only supportive
      therapy. The role of Cytomegalovirus (CMV) in the pathogenesis has been
      demonstrated by gastric biopsy in one third of the cases. Also other infectious,
      allergic and immunological factors have been hypothesized. We describe a case of
      hypertrophic gastropathy with important protein-loss, admitted to our Pediatric
      Department for evaluation because of vomit, weight loss, abdominal pain and
      hypoalbuminemia. Gastric mucosal biopsy revealed a morphological evidence of CMV
      infection.

PMID- 17533899
TI  - [Hemangiomas in infancy].
AB  - Hemangiomas are the most common tumors of childhood. Although most hemangiomas
      remain innocuous, a significant minority may be associated with important
      complications. The morphology and location of a hemangioma of infancy are
      critically important factors in determining potential risk for complications.
      Ongoing research on pathogenesis will provide new opportunities for
      interventional and preventive therapies.

PMID- 17533901
TI  - [Laparoscopic surgical treatment of anorectal malformations].
AB  - Anorectal Malformations (ARM) include a wide spectrum of anomalies, ranging from
      anal and rectal agenesis (usually associated with a recto-urethral, rectovaginal
      or recto-vestibular fistula) to ano-cutaneous fistula. On the basis of studies on
      the anatomy of the muscular structures contained in the pelvic cavity and on the
      physiology of the mechanisms which regulate the continence, many different
      techniques have been performed to allow a surgical treatment for the ARMs and to
      obtain post-operative results as nearer as possible to normality, that is to an
      adequate colic motility and a defecation control. In 2000, a new surgical
      technique for high and intermediate ARMs has been introduced, the
      laparoscopically assisted ano-rectal pull-through (LAARP) according to Georgeson.
      At the Department of Pediatric Surgery, Bologna University, from 2000 to
      nowadays, we have treated with LAARP 7 cases of high ARMs, all male patients and
      with colostomy. The average age at operation was between 2 and 10 months.

PMID- 17533900
TI  - The lumbar puncture in pediatric oncology.
AB  - In pediatric oncology, LPs are frequently performed for diagnostic and
      therapeutic purposes. A LP procedure may be helpful in diagnosing many diseases
      and disorders. In addition, a LP may be performed therapeutically, to inject
      medications directly into the spinal canal. Intrathecal administration of
      antineoplastic drugs allows to bypass the selective filter of BBB and to achieve
      significant concentrations of the antineoplastic agents in CSF reducing the
      likelihood of systemic toxicity. Lumbar puncture is generally well tolerated but
      might be characterized by several disadvantages and risks.

PMID- 17533902
TI  - Secondary prevention of latex allergy in children: analysis of results.
AB  - OBJECTIVE: Latex allergy has become an increasing and clinically important
      problem. Several recommendation for secondary preventive measures have been
      advised. The aims of the study were to illustrate the results of the latex-safe
      protocol and to evaluate in allergic patients the role of risk factors for the
      development of latex allergy. METHODS: Latex-safe treatment was divided into the
      following phases: anamnestic identification, allergologic assessment, patient
      selection, intervention programme, preventive medication, operating room
      equipment, postoperative management, patient and family training, follow-up.
      RESULTS: Between 1998 and 2004, 6.832 patients underwent 7.333 operations.
      Anamnestic and diagnostic tests showed that 26 patients had latex allergy. 44
      secondary perioperative latex-safe management have been accomplished in 26
      children. No allergic event or complications linked to the procedure occurred.
      Atopy, congenital malformations frequently associated with latex allergy and the
      presence of 5 or more surgical procedures were the major risk factors recognized.
      Six out of the 26 patients (23%) had only one risk factor (atopy). Twenty out of
      26 children (77%) had several associated risk factors: 8 of them had
      simultaneously 9 of the 10 analysed risk factors. Our data shows that, the higher
      their number, the higher the gravity of the allergy. CONCLUSIONS: Although latex
      allergy is a limited phenomenon, it is nevertheless quite frequent within risk
      groups. Most patients have simultaneously many risk factors for the development
      of such an allergy, and the occurrence of several risk factors increases severity
      of the allergy. Latex-safe perioperative management offers guarantees of safety
      against latex allergy phenomena.

PMID- 17533903
TI  - [Epidemiologic investigation of the pollen allergy to Cupressaceae in a
      population at risk for atopy].
AB  - The so-called emerging allergens have gained particular interest as causes of
      atopic diseases, and among these the cypress pollen. In fact, several allergens
      derived from the Cupressaceae family have appeared for the first time in new
      environments, thus causing unexpected phenomena. From May 2002 to May 2003 we
      have examined 560 patients who sought medical attention at the Center for
      allergic diseases in children. The patients came from various towns and villages
      from Southern Sardinia and all had undergone prick tests for inhaled allergens,
      irrespective of their complaints. The presenting symptoms were either respiratory
      (wheezing cough, rhinitis, asthma), cutaneous (eczema, nettle rash, angioedema)
      or ocular (conjunctivitis). All patients had a prick test for pollens (cypress,
      olive, wall pellitory, rag weed, composite, mix gross pollen), acari
      (Dermatophagoides farinae, Dermatophagoides pteronyssimus), dog and cat hair, and
      fungi (alternaria alternata, aspergillus fumigatus). Thirteen percent of patients
      (73/547) resulted allergic to cypress pollen, and three of them had a mono
      allergy (4,1%). Among these, one suffered bronchospasm, rhinitis and asthma more
      severe in January-February associated with recurring small eczematous lesions.
      Another one suffered bronchial asthma during winter months and the last one
      complained of rhinitis and nasal itching also during winter months.

PMID- 17533904
TI  - [Current trend in the diagnosis and treatment of primary non refluxing
      megaureter].
AB  - BACKGROUND: The terms megaureter or hydroureteronephrosis are non-specific
      because indicate various pathologic entities recognise different causes
      (obstruction, reflux, obstruction-reflux, primary and secondary). An undeveloped
      renal function in neonatal period makes more difficult the therapeutic approach.
      Actually the problem is to find the indicators that consent us the
      individualization of patients more suitable for nonoperative management. METHODS:
      From 1996 to 2002, we observed 60 patients with 74 megaureters. In 24 cases the
      diagnosis was antenatal, 6 cases were diagnosed immediately after birth, 13 in
      the first year of life and 17 after the first year (2y-10y). Patients were
      classified in two groups based on age; 43 cases diagnosed in the first year of
      life and 17 after. Both of them were classified in two further groups based on
      ureteral size and renal function, scintigraphically evaluated. RESULTS: In the
      first group (A) ureters with 10 mm of dilatation improved in 38.9% of the cases.
      Were stationary 50% and impaired 11,1% of them. Ureters with dilatation between 7
      and 10 mm improved in 24%, were stationary in 72% and impaired in in 4% of the
      cases. Ureters with less than 7mm dilatation improved in 35.2% and were
      stationary in 64.8%. In the group A renal scintigraphy MAG3 demonstrated, in the
      patients with acceptable renal function and washout, an improvement in 65% of the
      cases. Was stationary in 30% and impaired in 10%. CONCLUSIONS: The grade of
      dilatation evaluated with ultrasonographic exam and the study of renal function
      with diuresis renal scintigraphy using Tc-99m MAG3 and washout grade with
      diuresis renal scintigraphy are remarkable markers for the treatment choice.

PMID- 17533905
TI  - [Hexadactylism of the four limbs: a case report].
AB  - An unusual case of postaxial hexadactylism of the hands and feet in one female
      Caucasian neonate is described. The clinical picture was characterized by
      symmetrical duplication of the 5th finger in both hands and of the 4th finger in
      both feet. Malformations of the extremities both in the paternal and in the
      maternal family were reported. No other associated malformations have been found
      in the baby and her karyotype was normal. The performed analysis of the
      literature confirmed the peculiarity of the associated features of this case.

PMID- 17533906
TI  - [Autoimmune neutropenia: which therapy?].
AB  - We observed a case of primary autoimmune neutropenia in a 10-months-old girl
      affected by a 4 x 6 cm latero-cervical abscess caused by a Staphylococcus aureus
      infection. The severity of this finding prompted us to start a G-CSF treatment (5
      ug/Kg, 3 times-a-week). Granulocyte Colony Stimulating Factor immediately
      increased neutrophil count and led to a complete resolution of neutropenia in a 8
      months period of time.

PMID- 17533913
TI  - [Caring for conditions of shock].

PMID- 17533914
TI  - [The condition of shock, a therapeutic emergency].

PMID- 17533915
TI  - [Multiorgan failure and nursing care].

PMID- 17533916
TI  - [Analgesia/sedation in critical care].

PMID- 17533917
TI  - [Drug management via central and peripheral catheters in shock].

PMID- 17533918
TI  - [Management of cardiorespiratory arrest in critical care].

PMID- 17533919
TI  - [Emergency crash cart and its use in an academic medical center].

PMID- 17533920
TI  - [Non-medical cardiopulmonary resuscitation techniques].

PMID- 17533921
TI  - [Firefighter nurse, the French paramedical].

PMID- 17533922
TI  - [Family visiting 24 hours a day in adult critical care].

PMID- 17533923
TI  - [Coma and critical care, for a quality relationship management].

PMID- 17533924
TI  - [Ethics and resuscitation, limits and cessation of therapy].

PMID- 17533925
TI  - [Palliative care in critical care, from intentions to deeds].

PMID- 17533926
TI  - [International differences in end-of-life decisions].

PMID- 17533928
TI  - [Caring for conditions of shock].

PMID- 17533927
TI  - [Education of critical care nurses in Europe].

PMID- 17533929
TI  - [3/10 Organization of the campaign against nosocomial infections].

PMID- 17533930
TI  - [First aid].

PMID- 17533931
TI  - [3/3 Steroidal or glucocorticoid anti-inflammatories].

PMID- 17533932
TI  - Clinical implications of ethical concepts: moral self-understandings in children
      taking methylphenidate for ADHD.
AB  - Stimulant drug treatments for Attention Deficit/Hyperactivity Disorder (ADHD)
      have been a particular target of ethical controversy and debate. Bioethicists
      have raised concerns about the implications of stimulant drug treatment for child
      authenticity, individuality, and enhancement. There is at present little
      empirical evidence to support or deny these concerns. This article presents data
      from a pilot interview study that investigated children's moral self
      understandings in relation to ADHD diagnosis and stimulant drug treatment, with a
      focus on children's understandings of their authentic selves. Stimulant drug
      treatment does not appear to undermine a child's sense of personal authenticity:
      In this study, children reported that they believed a core dimension of their
      'real' selves was persistently 'bad', despite medication. This finding
      complicates two bioethical assumptions: That the authentic person is inherently
      good, and that there is inherent value in the experience of having access to a
      core, authentic dimension of oneself. Some important preliminary clinical
      implications of these findings are discussed.

PMID- 17533933
TI  - Whither authenticity: ADHD, medication, and Striving for the'good life'--a
      commentary on Singh.

PMID- 17533935
TI  - Consent and confidentiality in clinical work with young people.
AB  - Consent and confidentiality are increasingly important in clinical practice.
      However, the dilemmas faced by mental health practitioners can be highly complex
      and difficult to resolve. This difficulty is compounded by the fact that consent
      and confidentiality are subject to several different types of legislation based
      on different principles, and many of the policies which are formulated for
      general medical practice may not fit well with the mental healthcare context. The
      ethical principles, evidence base, legal context, developmental considerations
      and clinical context relevant to each situation must all be integrated, in
      consultation with children and adolescents and their parents, in order to arrive
      at a treatment plan which is sensitive to the views of all, developmentally
      appropriate for the children and adolescents, and responsive to changes in the
      situation or attitudes. We offer some practical approaches, including clinical
      practice algorithms, to consider the issues of consent and confidentiality in the
      child and adolescent mental healthcare setting.

PMID- 17533936
TI  - Reflecting teams with children: the bear necessities.
AB  - This article weaves research findings and clinical practice to address five
      ethical dilemmas: How to include children in sessions so that they feel listened
      to, appreciated and not judged; how to attend to children's feelings without
      making the focus solely their troubles; how to create a context in which children
      can express themselves when they cannot find the words; how to ensure a suitable
      time, place and relationship for talking; and how to create a safe context for
      respectful co-ordination between the different views of children and adults. A
      practical example including transcripts from sessions is presented. The authors
      show how a toy bear joining two therapists in a reflecting team can create
      opportunities for a 10-year-old girl and her parents to voice their different
      views and hear the different perspectives of each other. The parents, who
      generously agreed to share details of their family sessions, offered useful
      feedback on this write-up, suggesting that this article may be useful for staff
      and parents who join therapists in a playful approach to reflecting teams with
      children.

PMID- 17533937
TI  - Evidence-based and values-based policy, management and practice in child and
      adolescent mental health services.
AB  - Values-based practice is a new approach to working with complex and conflicting
      values. It is based, primarily, on learnable skills and is being applied across a
      range of policy, training and service development initiatives in mental health
      and social care. This article outlines some of the key features of values-based
      practice including its complementary relationships to both regulatory ethics and
      evidence-based practice. We describe the systemic links between values-based
      approaches at the three key levels of policy, service development, prioritization
      and commissioning, and clinical practice and managing delivery of services,
      particularly as they are being developed in child and adolescent mental health
      services. Our article concludes by indicating some of the areas for further
      development of values-based practice.

PMID- 17533938
TI  - Holding children in mind or holding therapy: developing an ethical position.
AB  - Attachment theory and therapy have established themselves as major constructs in
      foster care and adoption practice. The depth of the explanatory power of
      attachment theory and research have done much to both identify the source of
      developmental difficulties in adopted and fostered children, and of the
      significant changes that can be made when these children are placed with
      'autonomously' classified carers. However, the power of the concept has also led
      to a proliferation of ideas, particularly therapeutic models that can, in some
      cases, stray a long way from the core of what is effective, safe and ethical
      clinical practice. Holding therapy is one of these models. The British
      Association for Adoption and Fostering developed a position statement on this
      practice, setting it within a broader framework of assessment and intervention.
      But like the model, the development of the position statement became
      controversial in its development. The article charts some of the critical issues
      and identifies the very significant dilemmas for parents and carers caught up in
      the maelstrom of challenging behaviours and disturbing feelings. The conclusion
      turns to one of the key components of an attachment-based idea: The critical
      importance of finding the space to think and to feel what the child is
      communicating without resorting to dangerous retaliation.

PMID- 17533939
TI  - Clinical ethics committees: a practical response to ethical problems in clinical
      practice.
AB  - This article describes a recent development in the way in which ethical problems
      in clinical practice are being dealt with. The development of a network of
      Clinical Ethics Committees (CECs) across the UK is described, and the rationale
      for their emergence is explored. With the aid of a case example, two of the main
      methods available to CECs for analysis of cases referred to them are illustrated.
      A contrast is drawn between psychological and 'medical ethical' responses to the
      case example.

PMID- 17533940
TI  - The Bee Kind Garden: a qualitative description of work with maltreated children.
AB  - Although overwhelming numbers of children experience maltreatment in the U.S.A.,
      less than half receive mental health services. Furthermore, those seeking
      treatment frequently find a lack of available and/or appropriate services, thus
      many communities look for alternative ways to provide services to maltreated
      children. In this article we describe the Bee Kind Garden, an innovative project
      for maltreated children. Because the combination of strategies employed in the
      Garden was not found in any other comparable, published program, our goal is to
      describe the program from treatment providers' perspectives and to provide a
      theoretical basis for the program's conceptualization. We conducted
      semistructured interviews with providers from a wide variety of professional
      backgrounds and roles (e.g. child therapists, animal-assisted therapists,
      environmental educators). Through qualitative analyses, we identified five
      primary themes that encompassed providers' descriptions: Metaphorical
      environment, garden environment, one-on-one relationship, child-centered focus,
      and challenging representational models. Results and conclusions describing this
      innovative program are presented in the context of current child maltreatment
      literature. Discussion of collaboration between community-based organizations and
      academic researchers is suggested.

PMID- 17533941
TI  - Children's behaviour following diagnosis of acute lymphoblastic leukaemia: a
      qualitative longitudinal study.
AB  - Survival rates for children with cancer have improved significantly, but lengthy
      and painful treatments compromise the quality of life of children and their
      families. The aim of this article is to describe children's behaviour and coping
      over the 2- or 3-year-course of treatment. We interviewed 32 mothers of children
      newly diagnosed with Acute Lymphoblastic Leukaemia (ALL) shortly following
      diagnosis, 1 and 2 years later. Thematic analysis was used to extract themes
      related to adjustment and behaviour. The results were organized separately for
      children in three age groups: 0-4 years, 5-9 years and 10-14 years. Mothers
      described children in the 0-4-year age group as adjusting well, and attributed
      this to their limited understanding and ability to integrate treatments into
      normal life. Children in the 5-9-year group were adjusting less well,
      experiencing social problems and worries about appearance. Older children (10-14
      years) adjusted least well. Many withdrew socially and were concerned about the
      need to look and feel normal. These findings will be useful for parents and
      clinicians in identifying typical behaviours of children coping with ALL. They
      also have implications for the development of child-centred age-specific measures
      of quality of life in children treated for ALL.

PMID- 17533943
TI  - Research on the cost of providing family therapy: a summary and progress report.
AB  - This article provides a summary of effectiveness research on the costs of
      including family therapy in mental health services. Data was available from four
      different sources: (1) a large western Health Maintenance Organization with
      180,000 subscribers in the local Utah region; (2) the Medicaid system of the
      entire State of Kansas in the United States; (3) a US health insurance company
      with several million subscribers; and (4) a Family Therapy training clinic.
      Results suggest that family therapy reduces the number of health care visits,
      especially for high utilizers. These results were also replicated in a graduate
      student training clinic. Also, studies of two different health care systems (and
      a cost projection study) suggest that including family therapy as a treatment
      option does not significantly increase health care costs.

PMID- 17533942
TI  - Early predictors of helpless thoughts and behaviors in children: developmental
      precursors to depressive cognitions.
AB  - Learned helplessness behavior and cognitions were assessed in 95 kindergarten-age
      children during a series of impossible puzzle trials followed by a solvable
      puzzle trial. Latent growth curve analysis revealed reliable individual
      differences in the trajectories of children's affect, motivation, and self
      cognitions over time. Parents' reports of negative life events, harsh/negative
      parenting, and warm/positive parenting were associated with their children's
      learned helplessness behavioral trajectories and outcomes over the course of the
      puzzle trials. Results support speculations about the developmental origins of
      depressive explanatory or attributional style in children.

PMID- 17533944
TI  - [Collapse of medical system in Japan].

PMID- 17533945
TI  - [The value of long-term postoperative follow-up after curative resection of lung
      cancer and common problems associated with it].
AB  - This study was conducted to elucidate the real benefit of postoperative long-term
      surveillance for 10 years in patients who underwent curative resection for
      pathological stage I lung cancer. In 1995 and 1996, 100 patients with p-stage I
      lung cancer underwent curative resection. Of those, 20 patients were excluded
      because they did not comply with the follow-up regimen. Our follow-up regimen
      comprised a physical examination including a posterolateral chest radiograph and
      blood laboratory test every 6 months for up to 2 years, followed by once a year
      up to 10 years after resection. In addition, CT generally encompassed the lung
      apices to the lowest edge of the liver and was performed with intravenous
      contrast once every two years. As a result, among 80 patients, nine recurrences
      (11%) and seven metachronous second primary lung cancers (9%) were detected. Of
      16 malignancies detected, six underwent curative reoperation The 5-year survival
      rates after the discovery of recurrence and of second primary lung cancer were
      22% and 72%, respectively. The average survival of the six reoperated patients
      was 226 days longer than that of the remaining patients. For the calculation of
      the costs per life-year gained (LYG) of our follow-up program, an estimated
      survival benefit of 226 days was used. Consequently, the costs per LYG were
      calculated at almost 4,500,000 yen. In conclusion, the costs per LYG seem to be
      acceptable in the light of Japanese average annual earnings. In addition, this
      follow-up regimen seemed to show a clear survival benefit for patients with
      metachronous second primary lung cancer. However, for patients with lung cancer
      recurrence, the perceived benefit was nominal.

PMID- 17533946
TI  - [Follow-up examination and survival after treatment of primary breast cancer].
AB  - Frequent laboratory tests and diagnostic imaging examinations after primary
      treatment of breast cancer do not improve survival or influence the quality of
      life. The economic impact should be also taken into consideration. Intensive
      follow-up should not be recommended as a routine policy based on evidence-based
      medicine. However, patients usually want to be seen frequently by a physician and
      undergo diagnostic tests even though free of symptoms. This dilemma for
      oncologists has not been resolved.

PMID- 17533947
TI  - [Value of postoperative surveillance of tumor recurrence after curative
      esophageactomy].
AB  - A study of 256 patients whose dates and patterns of first mode of recurrence
      after curative esophagectomy from 1984 to 2004 revealed the recent improvement in
      survival after the detection of tumor recurrence. This tendency was evident in
      lymphatic recurrence, particularly in the cervical area. Lung metastasis was
      another mode of recurrence that has shown recent improvement. In this series, 20
      patients with lymph node metastases underwent reoperation for local or regional
      tumor control. The addition of systemic chemotherapy or chemoradiotherapy was our
      general rule. The 5-year survival rate after the detection of tumor recurrence in
      these 20 patients was 47.4%. Six with lung metastases in the group of patients
      whose esophagectomies were performed in the last 7 years underwent video-assisted
      pulmonary tumor resection. Five patients in this group are alive without signs of
      further recurrence for 92 to 1,437 days. The early detection of recurrent tumor,
      vigorous attempts to achieve locoregional control, and the addition of systemic
      chemotherapy are all important in achieving better results. We routinely perform
      conventional cervical and abdominal ultrasonography and computed tomography every
      6 months until 6 years after surgery is performed.

PMID- 17533948
TI  - [Evaluation and problems of follow-up surveillance after curative gastric cancer
      surgery].
AB  - Recurrence patterns after curative gastrectomy and follow-up surveillance were
      studied by referring to the literature. An analysis was done of 151 (11.5%)
      recurrent patients among 1,323 primary gastric cancer patients after curative
      (R0) resection. The recurrence rate was hematologic in 43%, peritoneal in 32.5%,
      and remote lymph node in 22.5%, although peritoneal recurrence was the most
      frequent in references. There were many peritoneal and remote lymph node
      recurrences in undifferentiated adenocarcinoma and hematologic recurrence in
      differentiated adenocarcinoma. In pT1, the hematologic recurrence rate was 90%
      and lymph node recurrence rate was 10%, which occurred even after 5 years. The
      frequency of peritoneal recurrence increased markedly in pT3. The rate of
      recurrence was 74.1% within 2 years and 88.1% within 3 years. There was no
      difference between lymph node, hematologic, and peritoneal recurrence in terms of
      survival time after surgery or even after recurrence. Referring to these results,
      follow-up surveillance programs for early and advanced gastric caner were
      developed. Surveillance will be continued for 10 years after surgery and mass
      survey or complete medical checkup is recommended 5 years after surgery. A
      standard follow-up program should exist, although it is not necessary for it to
      be the same in different institutes. There is as yet no consensus regarding
      intensive follow-up after curative gastrectomy because the evidence of efficacy
      is weak. In conclusion, a randomized, controlled trial of intensive follow-up is
      required to demonstrate the survival effect of surveillance.

PMID- 17533949
TI  - [Surveillance after curative resection for colorectal cancer].
AB  - Surveillance after curative resection for colorectal cancer is reviewed with
      special reference to the guidelines for colorectal cancer treatment issued by the
      Japanese Society for Cancer of the Colon and Rectum. The principal aim of
      postoperative surveillance in patients with colorectal cancer is to improve
      survival by early detection of a recurrence while it is still resectable. Meta
      analyses from Western countries demonstrated that intensive follow-up after
      curative surgery improves survival. In Japan, more intensive follow-up programs
      have been performed routinely than in Western countries. Although the impact of
      intensive follow-up on survival has not yet been clarified in a large-scale
      study, unified follow-up programs are suggested in the guidelines, based on the
      results of a large-scale, retrospective, multicenter study. The relapse rate in
      patients with Stage II, IIIa, and IIIb colorectal cancer increased rapidly during
      the first 3 years and gradually during the next 2 years. The relapse rate at 5
      years or later was less than 1%. The prognoses of patients who underwent curative
      resection for relapse were better than those who did not. Periodic follow-up for
      metachronous multicentric colorectal cancers should be recommended. Further
      studies will be necessary to validate the efficacy of intensive follow-up.

PMID- 17533950
TI  - [Surveillance after curative resection of hepatocellular carcinoma].
AB  - Among hepatocellular carcinoma patients, there is a distinct high-risk population
      for primary surveillance. Patients who underwent curative resection have a 5-year
      recurrence rate of as high as 70% and they are also considered to be at high
      risk. Based on currently available evidence, the recommended postoperative
      surveillance protocol is: monthly or bimonthly measurement of two tumor markers
      including alpha-fetoprotein and PIVKA-II, ultrasonography every 2 to 3 months,
      and enhanced CT every 6 months. This protocol may be too intense, but it is often
      requested by patients who have been informed about the nature of the disease and
      the high risk of recurrence. This intense protocol may detect tumor recurrence
      earlier and may provide a better chance for curative treatment. However, there is
      no sufficient evidence showing that this protocol confers survival benefit.

PMID- 17533951
TI  - [Concept and mechanism of bacterial translocation].

PMID- 17533952
TI  - [Therapeutics for bacterial translocation].

PMID- 17533953
TI  - [What we can learn from a case of medical malpractice--deaths from falling out of
      bed].

PMID- 17533954
TI  - [Systematic subsegmentectomy of the liver].

PMID- 17533955
TI  - [Multi-center survey of the use of synthetic surgical suture in cardiovascular
      surgery].

PMID- 17533956
TI  - [Ecology-car and heart--cardiovascular surgery in 21st century].

PMID- 17533957
TI  - [Factors related to experience of project development processes by municipal
      public health nurses in Japan].
AB  - PURPOSE: Public health nurses (PHNs) need to develop new projects to solve
      community health problems as an active strategy. The purpose of this study was to
      clarify how many Japanese PHNs actually have experience of project development
      process, and to examine related factors. METHOD: By using random-sampling, we
      chose 374 municipalities from a total of 1,871 that would not consolidate with
      their neighbours in 2005, and obtained cooperation from 305. In collaboration
      with the Association of Japanese Public Health Nurses, questionnaires mailed to
      2306 Japanese PHNs working in the municipalities in 2005. The self-administered
      questionnaire included items on; 1) municipal and organizational variables; 2)
      PHN-related factors; 3) whether the PHNs had experience of project-development
      processes. We performed logistic regression analysis to examine the relationship
      between experience and these parameters. RESULTS: Among the 1,270 respondents,
      PHNs who did not recognize the necessity of creating a new project accounted for
      481 (37.9%); those who recognized the need to create a new project but did not
      propose any practical means numbered 324 (25.5%); those who proposed a new
      project but did not implement it were 66 (5.2%); and those who provided a new
      project for their residents were 399 (31.4%). The logistic regression analysis
      revealed that PHNs who had experience of developing new services by themselves
      and read health, medical and welfare journals were significantly more likely to
      provide new projects for their residents. CONCLUSION: PHNs have the capability to
      create new projects and individuals in all municipalities and organizations need
      to acquire active experience of developing projects.

PMID- 17533958
TI  - [Epidemiological study of preferable life style for psychological health
      promotion].
AB  - OBJECTIVE: We sought to examine relationships of lifestyle factors, including
      diet, physical activity, sleep, alcohol consumption and smoking, with perceived
      stress and depressive symptoms. METHODS: Between 2001 and 2002, 7,947 men and
      women (mean 52.4 years) took part in examinations at the Osaka Medical Center for
      Health Science and Promotion. Lifestyle factors were determined by structured
      interview or by self-administered questionnaire. Associations of life style
      factors with perceived stress and depressive symptoms were tested by stepwise
      logistic regression analyses. RESULTS: Higher proportions of persons with
      depressive symptoms tended to be associated with higher proportions of persons
      with perceived stress. Among both men and women, low physical activity, lack of
      regular physical exercise, short sleeping time, to skip breakfast frequently, and
      having dinner within a couple of hours before going to bed were associated with
      both perceived stress and depressive symptoms. Men reporting between-meal or
      midnight snacks and having eating until they were full had higher odds ratios for
      perceived stress, while men conducting regular physical exercise and consuming 3
      or more dishes of vegetables per day had lower odds ratios for depressive
      symptoms. For women, high odds ratios for depressive symptoms and perceived
      stress were observed among those who tended to have salty foods (or frequent use
      of soy sauce) and a lower odds ratio for perceived stress was noted among persons
      who had soy products every day. CONCLUSION: Lifestyle facets such as skipping
      breakfast, low physical activity, and short sleeping time, appear to be
      associated with psychological health status of Japanese men and women.

PMID- 17533960
TI  - [Characteristics of respondents and nonrespondents to a mailed questionnaire for
      smoking behavior among post-discharge patients].

PMID- 17533959
TI  - [Excess mortality among 5,064 victims of arsenic poisoning from ingestion of
      arsenic-contaminated "Morinaga dry-milk" in 1955: a prospective study from 1982
      to 2004].
AB  - OBJECTIVES: A prospective cohort study was conducted to assess the excess
      mortality among victims of arsenic poisoning who had ingested "Morinaga dry-milk"
      that was contaminated with arsenic compounds in 1955. METHODS: We identified and
      enrolled 5,064 individuals who had ingested contaminated Morinaga dry-milk when
      they were aged two years or younger, in 1982 (mean age: 27.4 years) and they were
      followed until 2004 (mean length of follow-up: 22.3 years). The death
      certificates of subjects who died between 1982 and 2004 were examined. The risk
      of death was assessed by the ratio of the observed number (O) to the expected
      number of deaths (E), calculated from the mortality rate among Osaka residents.
      RESULTS: The O/E ratio for all causes of death was 1.3 (O = 211, P < 0.01).
      Significant excess mortality was observed for diseases of the central nervous
      system (O/E = 5.4) or circulatory system (O/E = 1.4), external causes (O/E = 1.4)
      and traffic accidents (O/E = 2.0). Excess mortality from all causes appeared 0 to
      4 years after study enrollment (O/E = 2.1, P < 0.01), and then the O/E ratio
      decreased to unity (O/E = 1.2) beyond 10 years after study enrollment. The 352
      males who were unemployed at the time of enrollment in the study showed
      significantly elevated risk of death from all causes (O/E = 3.3), death from
      disease of the central nervous system (O/E = 36.7), circulatory system (O/E =
      3.7) or respiratory system (O/E = 5.7), and death from external causes (O/E =
      3.4). CONCLUSION: This prospective cohort study showed that excess mortality from
      all causes among the victims of arsenic poisoning from ingestion of arsenic
      contaminated "Morinaga dry-milk" in 1955 decreased to unity when they reached
      middle age.

PMID- 17533961
TI  - Understanding treatment attitudes toward dementia: differences among community
      residents and health care professionals.
AB  - To examine how the severity of dementia affects attitudes to treatment
      preferences in a lay group of community residents and a group of medical care
      professionals who provide direct care to dementia affected patients. The
      participants were 259 community residents aged between 40 and 65, and 217 care
      professionals working at nursing homes or group homes. Respondents were randomly
      assigned to one of two scenarios involving moderate or severe dementia and each
      was asked questions about their preferences and attitudes to the employment of
      eight types of active treatments (ATs) to deal with a newly acquired illness as
      well as eight types of life-sustaining treatment (LST). Among the community
      residents, there were no significant differences in preferences toward any
      treatment items between the moderate dementia and severe dementia scenarios.
      Similarly, care professionals showed no significant differences in attitudes
      toward 15 of the 16 treatment items. The community residents had more negative
      attitudes than care professionals in attitudes to all types of LST, including
      four variations of AT that have a good chance of success. After dementia deprives
      an individual of decision-making capacity, progress of the disease has little
      effect on both community residents and care professionals' preferences. When
      discussing about end-of-life decision-making, care professionals need to be
      careful about the gaps in perception of good chance treatments with patients.

PMID- 17533962
TI  - [Can magnetic resonance imaging of the brain in the acute phase of carbon
      monoxide intoxication forecast delayed encephalopathy?].
AB  - We examined the usefulness of Magnetic Resonance Imaging (MRI) test in the acute
      phase of carbon monoxide intoxication for forecasting delayed encephalopathy
      (DE). [Case 1] 26-year-old female. COHb 12%. Takotsubo (Ampulla) cardiomyopathy
      was supervened. Pallidal disorder was recognized in MRI test in the early stage.
      Although Prophylactic HBO was performed, DE began. 36 days later, disorder was
      recognized in large area, such as, in cerebral white matter and callosum, and
      abnormality was found in WMS-R and MMSE. Since HBO was performed, DE subsided. In
      MRI test, on the other hand, high signal range in cerebral white matter and
      callosum were gradually decreased and WMS-R and MMSE were improved. [Case 2] 19
      year-old female. COHb 9.4%. The state was considered to be mild but pallidal
      disorder was found in MRI test at the beginning. DE did not start, then the part
      of pallidal disorder was narrowed. WMS-R and MMSE showed slightly low level.
      [Case 3] 19-year-old female. COHb 7.3%. The state was considered to be mild and
      there was no abnormal findings in MRI test in the early stage. DE did not start.
      [Case 4] 48-year-old male. COHb 48.9%. Rhabdomylosis was supervened, then
      ischemic change in a left radiate crown was recognized in the early MRI test.
      Since the third day, disorientation and restlessness had been developed, so that
      the patient was transferred to psychiatric department, though it was still
      difficult to distinguish the case from DE. Although the case is relatively mild,
      pallidal disorder is recognized in the early MRI test. Pallidal disorder alone
      can cause memory disorder and cognitive impairment. Even if pallidal disorder
      alone is recognized in the early MRI test, white matter disorder is developed
      with time, and then DE begins. If there are no typical carbon monoxide
      intoxication findings, some cases can be suspected as DE. It is useful to perform
      serial MRI test in order to prepare for delayed encephalopathy in carbon monoxide
      intoxication.

PMID- 17533963
TI  - [Diphenhydramine poisoning presented with psychotic-like symptoms and choreic
      involuntary movement: report of two cases].
AB  - We encountered two cases of diphenhydramine-containing hypnotics overdose,
      exhibiting delirium and involuntary choreic movement. In case 1, a 32-year-old
      man ingested 24 tablets of Drewell, each containing 25 mg diphenhydramine, in a
      suicidal attempt. About four hours after ingestion, he showed generalized
      convulsion, delirium, and involuntary choreic movements. Intravenous diazepam was
      ineffective and he was sedated with continuous infusion of propofol. About 15
      hours after ingestion and on discontinuing the sedation, he became alert and did
      not show any neurological abnormality. The blood concentration of
      diphenhydramine, measured by liquid chromatography/electrospray mass spectrometry
      (LC/MS), was 1.26 microg/ mL. In case 2, a 24-year-old woman ingested 114 tablets
      of Drewell and was admitted to our hospital. Her consciousness was impaired and
      she was treated with intravenous fluids. About four hours after ingestion, she
      became restless and showed confusion, agitation, and involuntary choreic
      movements. Sedation with continuous propofol infusion was required. She awoke the
      next day on discontinuing the sedation, and she did not show any neurological
      abnormalities. The blood concentration of diphenhydramine was 2.37 microg/mL. It
      is suggested that physicians should be aware of psychotic-like symptoms and
      choreic involuntary movement in patients with diphenhydramine-containing
      hypnotics overdose.

PMID- 17533964
TI  - [Case report of acute death on the 7th day due to exposure to the vapor of the
      insecticide chlorfenapyr].
AB  - We present the case of a 55-year-old male agricultural worker who complained of
      severe general fatigue and hyperperspiration after exposure to an insecticide
      vapor. He worked in a tea plantation and used chlorfenapyr, a broad spectrum for
      harmful insects, without any protective mask or clothes. After one day of
      insecticide spray work, he gradually began to complain of general fatigue,
      hyperperspiration, nausea and vomiting. At first, he was diagnosed as being
      dehydrated and was treated with fluid replacement therapy. Although he received
      this conservative therapy, there was no effect on the above mentioned symptoms.
      On the 7th day of the onset of his symptoms, his consciousness level deteriorated
      rapidly and body temperature exceeded 40 degrees C. No cerebral vascular disease
      or meningitis was observed. Finally, he died despite intensive care. The findings
      of the clinical course and laboratory data suggest a clinical diagnosis of acute
      pesticide poisoning due to exposure to chlorfenapyr vapor. We suggest that
      agricultural workers should use this insecticide with caution and sufficient
      protective gear.

PMID- 17533965
TI  - [Two cases of diphenhydramine related suicide].
AB  - Two suicidal cases associated with ingestion of diphenhydramine (DPH) were
      reported. Case 1 is a typical DPH overdose case of a young man with the blood DPH
      concentration of 12.2 microg/ mL. Case 2 is a double suicide of a man and a
      woman. They ingested DPH and fell asleep in a vehicle which had a cooking clay
      charcoal stove. Their blood DPH concentrations were 0.4 and 0.7 microg/mL, which
      were high enough to make them sleep. Their cause of death, however, was carbon
      monoxide poisoning with blood CO-Hb concentration of 14 and 19%. DPH is a low
      toxic agent and is available as an OTC drug in Japan. Similar fatal cases can be
      expected to happen in Japan.

PMID- 17533966
TI  - [Case of tetrodotoxin intoxication in a uremic patient].
AB  - Ingestion of certain types of puffer fish can result in severe and potentially
      lethal intoxication, referred to as tetrodotoxin (TTX) intoxication. It is well
      known that respiratory support plays a key role in the management of patients
      with TTX intoxication. We describe here the case of a 52-year-old uremic woman,
      who complained of numbness of the lips and weakness in the legs after ingestion
      of puffer fish (Lagocephalus wheeleri; called shirosaba-fugu in Japanese). While
      her symptoms were not severe and she did not require respiratory support, her
      condition did not improve after 2 days of hospitalization. Hemodialysis was
      therefore performed on hospital days 3, 4 and 5, and resulted in marked
      improvement of symptoms. We suggest that the patient's renal dysfunction caused
      an accumulation of TTX due to delayed excretion and thus modified the clinical
      course of TTX intoxication. Hemodialysis may be effective in the treatment of TTX
      intoxication. This is the first report of TTX intoxication in a uremic patient in
      Japan, and, importantly, the first report of intoxication with Lagocephalus
      wheeleri, which was previously considered to be a non-toxic species.

PMID- 17533967
TI  - [Lead in metal jewelry and others].

PMID- 17533968
TI  - [Proposal of an analytical pathway for the treatment of poisoning--8 lethal-level
      points to notice in analysis of postmortem specimens].

PMID- 17533969
TI  - [News from the Japan Poison Information Center. 2006 annual report JPIC].

PMID- 17533970
TI  - [Multislice CT--neuroradiological applications].
AB  - Invention of helical scan had introduced the concept of volumetric imaging.
      Ratest 64-rows multislice CT has made it possible to obtain high quality 3D CT
      angiography images in few seconds. In addition to morphological images of CNS
      (central nervous system), multislice CT provides functional information such as
      cerebral perfusion. Further advancement has been anticipated by the introduction
      of 256-rows area detector CT. Numbers of new applications such as dynamic 3D CT
      angiography, 3D CT-DSA (digital subtraction angiography), whole brain CT
      perfusion are expected to be in clinical use by area detector CT.

PMID- 17533971
TI  - [Applications of optical topography in neurosurgery].
AB  - Optical topography is a new alternative for noninvasive functional brain mapping.
      It uses near infrared light projected from the scalp into the brain. The
      reflected light which is sampled 30 mm apart from the injection probe carries the
      information of hemoglobin concentration change of the regional brain tissue lying
      at the midpoint of probes. When mapped using 24 channels, we see the real time
      brain activities during various tasks allowing the head movements as well. It is
      utilized in measuring the language function, and diagnosis of epilepsy focus.
      Several such clinical applications are demonstrated. The brain activities are
      measured during finger tapping. The mapping during word generation task shows the
      activities of Broca's area indicating the hemispheric dominancy of language
      function. We correlated the results between optical topography measurement and
      amytal test, showing 85% matching according to the language dominancy. It also
      useful in identifying the epilepsy focus because the hemoglobin increases at the
      focus region in the initial phase of epileptic seizures. In our study, the
      feasibility of optical topography in focus diagnosis is confirmed in 85% of 27
      cases. The advantages of optical topography are as follows. 1: It is portable to
      various clinical scenes including patient ward and outpatient clinic. 2: It can
      be used conjunction with fMRI and MEG. 3: It measures the brain activities even
      during the head movements.

PMID- 17533972
TI  - [Magnetic resonance diffusion tractography in the brain--its application and
      limitation].
AB  - Diffusion tractography of magnetic resonance imaging (MRI), such as diffusion
      tensor tractography, allows us to visualize white matter tracts in vivo and to
      study white matter integrity quantitatively. Virtual dissection of the living
      human brain can be performed in the first time. We developed tracking software,
      dTV and VOLUME-ONE, in 2001, as a freeware (http://www.ut
      radiology.umin.jp/people/masutani/dTV. htm), and we used it to visualize eloquent
      white matter bundles with relationship to brain tumors, cerebral infarctions and
      other lesions. We also used it for quantitative measurement of the specific
      tracts segmented by diffusion tensor tractography (tract-specific analysis) to
      reveal abnormalities in so-called normal appearing white matter. Three
      dimensional visualization of the white matter fibers such as corticospinal
      (pyramidal) tract, optic radiation and arcuate fasciculus with relationship to
      brain tumors such as gliomas was extremely helpful for preoperative evaluation
      and intraoperative navigation. We correlated tracking with intraoperative
      electric fiber stimulation to validate fiber tracking. In patients with small
      lacunar infarctions near the corticospinal tracts, relationship between the tract
      and fresh infarction correlated well with final (2 weeks-later) motor function.
      Quantitative measurement of the tract is a very sensitive tool. We analyzed the
      corticospinal and corticobulbar tracts in patients with amyotrophic lateral
      sclerosis (ALS). Changes of the diffusion parameters (fractional anisotropy and
      ADC) of the tracts were observed not only between normal controls but also
      between subtypes of ALS (limb- and bulbar-onset). Tract- specific analysis can
      also apply for the limbic-related tracts such as fornix, cingulum, uncinate
      fasciculus and etc. We observed differences in some of the fibers in
      neurocognitive/psychiatric patients such as schizophrenia and Alzheimer disease.
      Using fiber tracking, we can now develop white matter mapping. We visualized
      components of the pyramidal tract (fibers from foot, hand, face motor areas
      separately) and made a probabilistic map. Diffusion tractography is a unique tool
      to visualize and segment the white matter pathways and one can evaluate the
      segmented tract quantitatively. Importance of this tool will become more
      significant in clinical and neuroscience fields in the future.

PMID- 17533973
TI  - [Clinical applications of 3.0 T magnetic resonance system in the
      neuroradiological field].
AB  - Recently, the introduction of 3 tesla (3T) magnetic resonance (MR) system for
      more sophisticated clinical applications has yielded in important benefits,
      especially in neuroradiology. The aim of this article is to illustrate the
      practical scientific applications of the 3T system in the neuroradiological
      filed. From the clinical point of view, we focused on the usefulness of 3T system
      for the diagnosis of several neurological disorders, such as brain tumors,
      vascular lesions, hemorrhagic lesions, acute cerebral infarcts and degenerative
      diseases. The greatest advantage of high-field MR system is a higher signal to
      noise ratio. This higher spatial resolution can provide precise anatomical
      information for brain tumor itself and its surrounding structures. Diffusion
      weighted imaging (DWI) also benefits from the higher signal to noise ratio and
      offers useful information for tumor characteristics. Navigation system with
      diffusion tensor tractgraphy is also available for surgical operation of brain
      tumors. Parallel imaging enables to improve the quality of tractgraphy by
      reducing susceptibility artifacts. 3T TOF (time-of-flight) MR angiography (MRA)
      demonstrates superior depiction of intracranial aneurysms compared with that of
      1.5T TOF MRA. 3T TOF MRA is also useful for the evaluation and follow-up of
      stenoocclusive diseases including moyamoya disease. Susceptibility weighted
      imaging (SWI) is a BOLD (blood oxygenation level dependent)-sensitive method for
      visualizing anatomical features such as small cerebral veins in high detail.
      Therefore, 3T system has advantages for obtaining detailed, high spatial
      resolution images of the venous network. SWI is useful for detection of
      hemorrhagic lesions and early diagnosis of acute hemorrhagic infarcts. SWI also
      can detect embolus and evaluate functional changes showing dilatation of
      medullary veins in the area of acute cerebral infarcts. Neuromelanin imaging
      using 3T system can directly demonstrate the locus ceruleus and substantia nigra
      by the neuromelanin content and have the potential to become a powerful tool in
      Parkinson's disease and other neurodegenerative disorders with Parkinsonism.
      Hyperintense putaminal rim can be often observed in clinically normal subjects on
      fast spin echo T2-weighted images at 3T system. This finding should not be
      mistaken for multiple system atrophy. 3T MR system indeed offers new potential
      because of a substantial increase in signal intensity provided by the higher
      magnetic field. Routine neuroradiologic imaging would benefit from higher
      magnetic field. However, It is required that extended knowledge of clinical data
      in comparison with 1.5T system to elucidate the efficacy of 3T system in the
      neuroradiology.

PMID- 17533974
TI  - [Neurological diseases and SPECT--analysis using easy Z-score imaging system
      (eZIS)].
AB  - We developed a method for automated diagnosis of brain perfusion SPECT and
      designated this method as an easy Z-score imaging system (eZIS). In this software
      program, voxel-by-voxel Z-score analysis after voxel normalization to global mean
      or cerebellar values; Z-score = ( [control mean] - [individual value] )/ (control
      SD) is performed. These Z-score maps are displayed by overlay on tomographic
      sections and by projection with averaged Z-score of 14mm thickness to surface
      rendering of the anatomically standardized MRI template. Anatomical
      standardization of SPECT images into a stereotactic space is performed using
      statistical parametric mapping (SPM) 2. This program has an advantage of
      capability of incorporation of SPM results into automated analysis of Z-score
      values as a volume of interest (VOI). A specific VOI can be determined by group
      comparison of SPECT images for patients with a neuropsychiatric disease with
      those for healthy volunteers using SPM. Even if a center can construct a normal
      database with good quality comprising a large number of healthy volunteers, other
      centers have not been able to use this normal database because of differences
      between the used gamma cameras, collimators and physical correction algorithms.
      Since SPECT exhibits greater variations in image quality among different centers
      than PET, conversion of SPECT images may be necessary for sharing a normal
      database. In this eZIS software, we incorporated a newly developed program for
      making it possible to share a normal database in SPECT studies. A Hoffman 3
      dimensional brain phantom experiment was conducted to determine systematic
      differences between SPECT scanners. SPECT images for the brain phantom were
      obtained using two different scanners. Dividing these two phantom images after
      anatomical standardization by SPM created a 3-dimensional conversion map. The use
      of a conversion map obtained from SPECT images of the same phantom provided very
      similar SPECT data despite extreme differences between scanners. The present
      method may be useful for combining normal databases from different centers and
      greatly enhance the diagnostic value of brain SPECT imaging by standardization of
      data analysis using a common normal database.

PMID- 17533975
TI  - [Positron emission tomography with FDG and newly developed tracers for the
      assessment of brain metabolism and synaptic function in neurological disorders].
AB  - Positron emission tomography has enabled us to measure various fundamental
      parameters of human brain physiology and chemistry, such as cerebral blood flow,
      metabolism and synaptic functions. Blood flow and oxygen metabolism is important
      for the understanding of cerebro-vascular disease. Glucose metabolism is tightly
      coupled with brain function and FDG-PET is useful for the determination of
      epileptic foci and for the evaluation of tumor malignancy. Imaging analysis of
      functional neuroanatomy of these parameters is very promising for the early
      diagnosis of dementia, such as Alzheimer's disease. Measurement of pre- and post
      synaptic function is applicable to the differential diagnosis of parkinsonism. In
      early stage of Parkinson's disease, only presynaptic dopaminergic function is
      impaired, while in multiple system atrophy with striato-nigral degeneration type,
      both pre-and post dopaminergic function is reduced. Development of new
      radiotracers is expected for detection of early specific pathological changes and
      more previous changes underlying the deterioration of neurochemistry, such as
      genetic abnormalities.

PMID- 17533976
TI  - [Insights into auto-transplantation--the unexpected discovery of
      transdifferentiation systems in bone marrow stromal cells and its application].
AB  - Many kinds of cells, including embryonic stem cells and tissue stem cells, have
      been considered candidates for cell transplantation therapy for muscle
      degenerative diseases. Bone marrow stromal cells (MSCs) also have great potential
      as therapeutic agents since they are easily isolated and can be expanded from
      patients without serious ethical or technical problems. Recently, new methods for
      the highly efficient and specific induction of functional skeletal muscle cells
      have been found in MSCs. Induced cells differentiate into muscle fibers upon
      transplantation into degenerated muscles of rats and mdx-nude mice. Furthermore,
      the induced population contained Pax7-positive cells that contribute to
      subsequent regeneration of muscle upon repetitive damage without additional
      transplantation of cells. Here I describe the discovery of these induction
      systems and focus on the potential use of MSC-derived cells for "auto-cell
      transplantation therapy" in muscle-degenerative diseases.

PMID- 17533977
TI  - [Neuronal mechanism of functional recovery of dexterous finger movements after
      lesion of the corticospinal tract--studies in a non-human primate model].
AB  - Neuro-rehabilitation is based on the concept that training recruits the remaining
      neuronal systems to compensate for partial injury of the CNS. However, the
      neuronal basis of such take-over mechanism is poorly understood. As an
      experimental model of functional compensation after injury, we are studying the
      functional recovery after lesion of the direct cortico-motoneuronal (CM) pathway
      in macaque monkeys. It has been generally believed that direct CM pathway is
      essential for the control of independent control of individual fingers, such as
      precision grip. However, recent studies from our group have demonstrated the
      existence of a disynaptic excitatory CM pathway in macaque monkeys, which is
      mediated by propriospinal neurons in the C3-C4 segments (C3-C4 PNs). To
      investigate the possible function of the indirect pathway via the C3-C4 PNs,
      performance of reaching and grasping movements was tested in monkeys with lesion
      of the direct pathway by transection of the dorsolateral funiculus of the spinal
      cord at the border between C4 and C5 segments. Interestingly, the ability of
      precision grip recovered in a few weeks to 1-3 months after the lesion, which
      suggested that the indirect CM pathway can mediate the command for dexterous
      finger movements. We have found that the functional recovery is accompanied by
      enhanced signal transmission in the indirect CM pathway, presumably at the spinal
      level. Based on these experimental evidence, the neural substrate for functional
      compensation will be discussed.

PMID- 17533978
TI  - [A comparison study of aspiration with clinical manifestions in stroke patients].
AB  - This study was investigated clinical factors for aspiration in stroke patients by
      videofluoroscopy (VF). Subjects were 102 patients with strokes aged between 34
      and 101 years including 72 males and 30 females and for whom VF was performed for
      swallowing difficulty or suspected swallowing difficulty. They consisted of 64
      patients with cerebral infarction, 33 patients with cerebral hemorrhage, and 5
      patients with subarachnoid hemorrhage. Before VF, pharyngeal reflex, physical
      status, and cognitive function were evaluated as bedside clinical assessment. As
      for swallowing evaluation at bedside, the repetitive saliva swallowing test
      (RSST) and water swallowing test were performed. Aspiration was classified into
      aspiration with choking and silent aspiration (SA) by presence of a cough reflex.
      As results, aspiration with foodstuffs on VF was found in 59 of 102 (57.8%)
      patients and SA was found in 44 of them (43.1%). In patients with not only
      pharyngeal reflex but also cervical and maintaining a position stability, and
      those who were decreased in cognitive function, aspiration should always be
      supposed and the observation for eating behavior against aspiration should be
      needed. We divided patients into three groups; no aspiration, SA and aspiration
      with choking. Significant difference was observed between the groups in Mini
      Mental State Examination, Barthel Index, and RSST. Although in the water
      swallowing test, swallowing was possible without choking, SA was observed on VF
      in most cases. Therefore, in cases with serious disability and cognitive
      dysfunction with advanced age, RSST and water swallowing test should not be
      overestimated, it is worth conducting VF when aspiration is suspected from
      neurological assessment.

PMID- 17533979
TI  - [Successful use of methylprednisolone therapy in a case of non-herpetic acute
      encephalitis with antibodies against ionotropic glutamate receptor epsilon2 and
      delta2].
AB  - This report concerns a 32-year old man with non-herpetic acute limbic
      encephalitis. He was admitted to our hospital because of high fever and
      consciousness disturbance. Cranial MRI revealed abnormal signal intensities in
      the bilateral mesial temporal lobes. On the second hospitalization day, he
      developed status epilepticus, which necessitated general anesthesia. Following
      administration of intravenous (IV) methylprednisolone pulse therapy (1 g/day, 3
      days), his consciousness disturbance began to improve. Treatment with high-dose
      IV methylprednisolone was continued for about 2 weeks, but on the 7th day, he
      showed severe anterograde amnesia and retrograde amnesia regarding the preceding
      5 or 6 years. Subsequently, however, his amnesic disorders improved markedly, and
      on the 46th day, memory dysfunction had disappeared. Autoantibodies against the
      glutamate receptor subunits epsilon2 and delta2 were detected in both the CSF and
      serum, but these antibodies in the CSF became normal during the clinical course.
      The voltage-gated potassium channel antibody was negative. This case report
      indicates that high-dose IV methylprednisolone therapy may be an affective
      treatment for non-herpetic acute limbic encephalitis, possibly associated with
      autoimmune mechanisms.

PMID- 17533980
TI  - [A case of multiple sclerosis with alien hand (diagonistic dyspraxia)].
AB  - In this paper, we describe a case of mutiple sclerosis (MS) with diagonistic
      dyspraxia and the callosal lesions in MRI. The patient was a 54-year-old woman
      with 12 year-history of suffering from MS. Her clinical symptoms were left alien
      hand, mild euphoria, right blindness, left visual deficit (0.06), mild weakness
      of right upper limb, complete paraplegia of lower limbs, total sensory deficit
      below middle sternal level and neurogenic bladder. She was right-handed person
      and her alien hand was such a manner; when she intended to use spoon with right
      hand, her left hand aimlessly began to hold and release a cup or dish. Then, she
      was diagnosed as diagnostic dyspraxia. Neuropsychological examinations disclosed
      left hemispheric dysfunction including left hand agraphia and disconnection of
      the callosum. MRI showed patchy lesions in the callosum, right optic radiation,
      both side thalamus (left > right), left cerebral peduncle, and spinal cord of
      cervical to the thoracal portion. Although the functional disorders and the
      radiological atrophy of the callosum, the clinical manifestation of the callosal
      disconnection in MS cases has been scarcely reported, and this case seems to be a
      quite rare condition to be described.

PMID- 17533981
TI  - [Granulomatous angiitis of the CNS associated with cerebral amyloid angiopathy-
      an autopsied case with widespread involvement].
AB  - The patient was a 69-year-old woman without history of dementia who developed
      meningoencephalitis with initial signs of headache and disturbance of
      consciousness. In this time any abnormal lesions were admitted. Five weeks later,
      she developed bleeding from the right parietal lobe and underwent surgical
      removal of hematoma and brain biopsy at another hospital. The pathological
      specimen revealed beta-amyloid (Abeta) deposition in the pial vascular wall,
      perivascular invasion of multinucleated giant cells and lymphocytes, and the
      presence of numerous microinfarcts in the brain parenchyma. In response to pulsed
      steroid therapy, transient and slight improvement of level of consciousness was
      noted, but she died of pneumonia 12 weeks after disease onset. On post-mortem
      examination, widespread multinucleated giant cell granulomatous angiitis
      accompanied by Abeta deposition was found extensively even in the sacral cord. In
      addition, groups of tau-positive degenerated nerve processes without Abeta
      deposition were found scattered in the cerebral cortex.

PMID- 17533982
TI  - [Wnt/beta-catenin signaling pathway and drug discovery].

PMID- 17533983
TI  - [Advanced medicine and innovative technology].

PMID- 17533984
TI  - Reduction of dioxins and polychlorinated biphenyls (PCBs) in human body.
AB  - The accumulation of persistent lipophilic organic pollutants like dioxins and
      PCBs in human body is of great concern since many of these compounds may elicit
      adverse health effects on humans. To reduce dioxins and PCBs with long half-lives
      that are absorbed into the human body, we need to work actively to minimize
      accumulation of dioxins and PCBs taken. Lot of manner has been tested such as
      foods containing dietary fibers and chlorophyll, lipids (squalane etc) and anion
      exchange resins. Cholestyramine, a cholesterol lowering agent, was no efficacy in
      humans. Authors have conducted a pilot study to demonstrate the effect lowering
      dioxin in human bodies using colestimide. Nine patients on cdestimide for 6
      months, showed mean 20% decrease respectively in both dioxin and PCB levels, and
      the maximum percentage decrease was approximately 40%. From a standpoint to avoid
      the influence on high-risk group and high-risk life stage other than next
      generation, the world-wide cooperation for reducing environmental chemicals is
      greatly appealed.

PMID- 17533985
TI  - Local cytomegalovirus infection in patients with diarrhea following allogeneic
      stem cell transplantation.
AB  - To evaluate local cytomegalovirus (CMV) infection in patients who developed
      diarrhea after allogeneic hematopoietic stem cell transplantation (HSCT),
      histologic and molecular analysis was carried out with intestinal biopsy samples.
      from 17 transplant recipients. A CMV-specific intranuclear inclusion body
      indicating intestinal CMV disease was documented in 2 biopsy samples. CMV DNA was
      detected by quantitative polymerase chain reaction in 8 of 23 (34.8%) samples,
      including 2 samples diagnosed with intestinal CMV disease. Of 15 patients without
      histologic confirmation of intestinal CMV disease, pre-emptive therapy was
      carried out for 8 patients based on positive antigenemia, and for 2 patients on
      positive CMV DNA, respectively. Intestinal CMV disease was successfully treated
      with antiviral therapy for 2 patients and prevented with pre-emptive therapy
      based on either positive antigenemia or positive CMV DNA for 10 patients.
      Endoscopic examinations with histologic and molecular analysis may be important
      in the early treatment and the prevention of intestinal CMV disease in patients
      with diarrhea after allogeneic stem cell transplantation.

PMID- 17533986
TI  - [Applicability of voice acoustic analysis with vocal loading testto diagnostics
      of occupational voice diseases].
AB  - BACKGROUND: An assessment of the vocal system, as a part of the medical
      certification of occupational diseases, should be objective and reliable.
      Therefore, interest in the method of acoustic voice analysis enabling objective
      assessment of voice parameters is still growing. The aim of the present study was
      to evaluate the applicability of acoustic analysis with vocal loading test to the
      diagnostics of occupational voice disorders. MATERIAL AND METHODS: The results of
      acoustic voice analysis were compared using IRIS software for phoniatrics, before
      and after a 30-min vocal loading test in 35 female teachers with diagnosed
      occupational voice disorders (group I) and in 31 female teachers with functional
      dysphonia (group II). RESULTS: In group I, vocal effort produced significant
      abnormalities in voice acoustic parameters, compared to group II. These included
      significantly increased mean fundamental frequency (Fo) value (by 11 Hz) and
      worsened jitter, shimmer and NHR parameters. Also, the percentage of subjects
      showing abnormalities in voice acoustic analysis was higher in this group.
      CONCLUSIONS: Conducting voice acoustic analysis before and after the vocal
      loading test makes it possible to objectively confirm irreversible voice
      impairments in persons with work-related pathologies of the larynx, which is
      essential for medical certification of occupational voice diseases.

PMID- 17533987
TI  - [Underestimation of exposure incidence rates in Polish health workers: a
      prospective study].
AB  - BACKGROUND: Analyses of exposure rates among health care workers comprise both
      risk and epidemiology of blood borne pathogenic factors. In Poland, a possible
      extent of underestimation of such incidents has not yet been widely studied in
      the population of this group of employees. The aim of the study was to observe a
      group of population chosen as an example to assess the actual exposure incidence
      rates, especially those not subjected to registration. MATERIALS AND METHODS: A
      prospective six-month survey covered 319 Lower Silesia health care workers:
      physicians, nurses and auxiliary staff. Statistical methods were used to analyze
      the obtained data, especially those concerning the job performance, the number of
      medical procedures performed and frequency of exposures, both registered in each
      case and not registered in the post-exposure prophylaxis log. RESULTS AND
      CONCLUSIONS: Finally, 269 persons were under observation. Actual exposure
      incidence rate was several fold higher than that officially registered and
      differed depending on the department and subgroup of health care workers. In
      summary, the ratio of all the registered cases to those not registered was 1: 6.
      An overall proportion of not registered cases of exposure was as high as 86%.
      Most frequent job activities of exposed health care workers comprised preparatory
      procedures like parenteral drug administration or injections. Post-procedure
      activities were less frequently the cause of exposure. Non-registration of such
      exposures were motivated by a self-assessment of a low infection risk or a
      conviction that self-protection on the incidence site was optimal. Lack of
      current knowledge was rather rarely admitted as a reason for underreporting.

PMID- 17533988
TI  - [Knowledge, hygiene behavior and risk of bloodborne infections in the selected
      staff of beauty parlors and hairdressing salons].
AB  - BACKGROUND: The aim of the study was to examine hygiene practices and risk
      factors for bloodborne infections in the selected staff of beauty parlors and
      hairdressing salons. MATERIAL AND METHODS: In this study, 118 people (112 women
      and 6 men), aged 18-55 years, were surveyed. The majority of the respondents (76
      people) fell within the 20-29 age group. RESULTS: Negligence in obeying some
      rules of work hygiene were found in the surveyed group of workers; at the same
      time most of the parlors and salons met legal requirements concerning sanitation
      and equipment hygiene. Of the total group of respondents, 53% of the staff
      employed in beauty parlors and hairdressing salons replied "Yes" to a question on
      incidents of sharp injuries during typical work activities over the last 2 years.
      The staff of hairdressing salons reported more accidents of this kind.
      CONCLUSIONS: It is necessary to teach this group of employees about hygiene and
      sanitary practices. The current state of affairs in this small, but quite
      representative occupational group shows considerable ignorance in this regard. As
      for sanitation and disease control, special attention must be paid to the
      constant observance of hygiene rules at work. In particular, hands should be kept
      clean, gloves should be worn and adequate microbiological cleanliness of tools
      should be ensured. Inspection services should pay particular attention to whether
      the rules of handling used materials, a potential source of infection, are obeyed
      by workers. The results of numerous studies show that a large majority of parlors
      and salons to cut their operating costs do not follow relevant regulations in
      force. Incidents of staff exposure to potentially infectious material are usually
      connected with mechanical skin injuries. Contact with mucous membranes is less
      frequent. It should be pointed out that employees failed to wear protective
      gloves during incidents of exposure to potentially infectious material. Scissors,
      the major tool used by the staff of hairdressing salons were most frequently the
      cause of injuries.

PMID- 17533989
TI  - [Exposure assessment to bioaerosols among sewer workers].
AB  - BACKGROUND: The purpose of the study was to evaluate exposure to bioaerosols
      among sewer workers. MATERIALS AND METHODS: The study was carried out in the
      summertime, based on the standard PN-EN 13098. Air samples were collected on
      gelatine filters at three stationary sites: inside the sewer, next to the sewer
      manhole during under pressure cleaning and at effluent discharge point. In
      collected samples the qualitative and quantitative analysis of bacteria and fungi
      were performed. RESULTS: Bacteria and fungi concentrations were at low levels.
      The highest concentration of bacteria (about 5.0 x 10(2) cfu/m3) was found inside
      the sewer and of fungi (about 1.0 x 10(2) cfu/m3) at effluent discharge point.
      Among all determined microorganisms Gram-positive bacteria were predominated,
      especially Staphylococcus lentus. Others bacteria there were also found, like rod
      shaped of the genus Bacillus and Enterococcus faecalis. The diversification of
      Gram-negative bacteria was small. Among fungi there were determined
      representatives of two genera Aspergillus spp. and Penicillium spp., including
      species Aspergillus fumigatus. CONCLUSIONS: According to the law in force among
      all determined microorganisms only bacteria Enterococcus faecalis (Enterococcus
      spp.) and mould Aspergillus fumigatus are classified as harmful biological agents
      (occupational risk group 2). It is suggested using by employees personal
      protective equipment, especially for respiratory airways and skin protection and
      also keeping the rules of individual hygiene.

PMID- 17533990
TI  - [Biological hazards in air at municipal waste landfills].
AB  - OBJECTIVES: The aim of the study was to assess the microbiological air quality at
      the selected municipal waste landfills. MATERIALS AND METHODS: The study was
      conducted during the summer at two municipal landfills. Air samples were
      collected on agar plates. The evaluation was based on the concentration levels of
      airborne bacteria and fungi and the identification of isolated strains. RESULTS:
      The total number of bacteria and fungi did not exceed the level of 10(3) cfu/m3.
      The highest concentrations of bacteria in air were observed during unloading,
      disposing and compacting of municipal wastes (landfill 1 - 6,1 x 10(3) cfu/ml,
      landfill 2 - 5,4 x 10(2) cfu/m3). The highest concentrations of fungi in air were
      observed at filled up parts of the landfills (landfill 1 - 4,8 x 10(2) cfu/m3,
      landfill 2 - 1,2 x 10(3) cfu/m3). The qualitative analysis of the air samples
      indicated the presence of 21 bacterial and fungi. Among of them bacteria
      Enterococcus faecalis, Enterobacter cloacae, Escherichia coli, Klebsiella
      pneumoniae, Klebsiella oxytoca, Proteus mirabilis and fungi Aspergillus
      fumigatus, Candida albicans are classified as harmful biological agents.
      CONCLUSIONS: The total number of bacteria and fungi in air samples collected at
      the selected municipal waste landfills did not exceed the reference values. The
      concentration levels of bioaerosols are diversified according to the size of the
      landfill, the total number of accumulated wastes and the level of area usage. It
      is suggested using by municipal waste workers personal protective equipment,
      especially for respiratory airways and skin and also keeping the rules of
      individual hygiene.

PMID- 17533991
TI  - [Effectiveness of preventive actions for lead exposed workers: an assessment
      based on biological monitoring].
AB  - Biological monitoring plays a significant part in the assessment of occupational
      exposure to lead. The method basically comprises determinations of blood lead
      concentration and of one of early toxic-effect biomarkers: the level of either
      zincprotoporphyrin (ZnPP) in blood or deltaaminolevulinic acid (ALA) in urine.
      However, biological monitoring is conducted only in 25% of all industrial plants,
      where the employed technological processes are the source of occupational lead
      exposure. The project that has been implemented by the Nofer Institute of
      Occupational Medicine, Lodz, Poland and Outpatient Clinic for Occupational
      Health, Poznan, Poland, since 1997 made it possible to assess the dynamics of
      lead exposure in one of the largest battery plants in Western Poland. Based on
      the analysis of blood lead determinations in lead-exposed workers, the authors
      could trace the effectiveness of the project aimed at reducing lead exposure in
      the plant. The findings revealed that the preventive measures applied over the
      years 1997-2005 resulted in a considerably decreased percentage of blood lead
      concentrations exceeding the relevant BEI (biological exposure index) value of
      500 microg/l: from 19% in 1997 to 1% in 2005. Such a high effectiveness of the
      project can be mostly attributed to a successful cooperation between the
      occupational physician, in-plant occupational health services, and the employer.
      They were all actively involved in a wide-range of activities for workers' health
      protection and workplace health promotion.

PMID- 17533993
TI  - [The role of psychological factors and psychiatric disorders in skin diseases].
AB  - In this paper, the relation between psychological factors and psychiatric
      disorders in patients with skin diseases is discussed. On the one hand
      psychological factors (stress, negative emotions) can influence the generation
      and aggravation of skin disorders (urticaria, atopic dermatitis, vitiligo), on
      the other hand psychological disorders can result in some skin diseases
      (psoriasis, atopic dermatitis). In the majority of cases the quality of life is
      poorly estimated by patients with skin problems. Psychodermatology is divided
      into three categories according to the relationship between skin diseases and
      mental disorders: 1) psychophysiologic disorders caused by skin diseases
      triggering different emotional states (stress), but not directly combined with
      mental disorders (psoriasis, eczema); 2) primary psychiatric disorders
      responsible for self-induced skin disorders (trichotillomania); and 3) secondary
      psychiatric disorders caused by disfiguring skin (ichthyosis, acne conglobata,
      vitiligo), which can lead to states of fear, depression or suicidal thoughts.

PMID- 17533992
TI  - [Mechanisms and toxic effects of lead on the cardiovascular system].
AB  - Exposure to lead is still one of essential health problems in our country.
      Current views on mechanisms and toxic effects of lead on the cardiovascular
      system are presented. Special attention is paid to changes in the heart
      morphology and physiology resulting from long-term exposure to lead, the effect
      of lead on the muscular coat and endothelium of blood vessels, changes in the
      metabolism of erythrocytes, leukocytes and thrombocytes in persons chronically
      exposed to lead as well as to the relation between lead and hypertensive and
      atherosclerotic illnesses induced by changes in the structure and function of the
      cardiovascular system. The described effects of lead exposure should encourage us
      to further reduction of occupational and environmental exposure to this metal and
      controversies that still exist to continue research in this field.

PMID- 17533994
TI  - [Assessment of health risk of sevoflurane and isoflurane exposure among surgical
      staff: a problem for employers].
AB  - Sevoflurane and isoflurane are polyfluorinated anesthetics used during surgical
      treatment of both adults and children. They are usually applied as mixtures with
      oxygen or dinitrogen monoxide. An assessment of health risk of exposure to these
      inhalant anesthetics poses a serious problem for employers, mostly due to the
      fact that maximum admissible concentrations (MAC) for these compounds have not
      been established. Consequently, there is no obligation to measure their air
      concentration in the workplace. However, the employer is responsible for
      determining whether or not a given hazardous agent is present in the work
      environment. The setting of MAC values for sevoflurane and isoflurane has
      recently been considered by the Expert Group for Chemical Hazards that proposed
      to accept 55 mg/m3 (7 ppm) and 32 mg/m3 (4 ppm), respectively as MAC values in
      assessing workplace hazards. These exposure levels should protect the surgical
      staff from adverse neurological, cardiovascular, respiratory, and irritant
      effects.

PMID- 17533995
TI  - [Calculation of workers' health care costs].
AB  - In different health care systems, there are different schemes of organization and
      principles of financing activities aimed at ensuring the working population
      health and safety. Regardless of the scheme and the range of health care
      provided, economists strive for rationalization of costs (including their
      reduction). This applies to both employers who include workers' health care costs
      into indirect costs of the market product manufacture and health care
      institutions, which provide health care services. In practice, new methods of
      setting costs of workers' health care facilitate regular cost control,
      acquisition of detailed information about costs, and better adjustment of
      information to planning and control needs in individual health care institutions.
      For economic institutions and institutions specialized in workers' health care, a
      traditional cost-effect calculation focused on setting costs of individual
      products (services) is useful only if costs are relatively low and the output of
      simple products is not very high. But when products form aggregates of numerous
      actions like those involved in occupational medicine services, the method of
      activity based costing (ABC), representing the process approach, is much more
      useful. According to this approach costs are attributed to the product according
      to resources used during different activities involved in its production. The
      calculation of costs proceeds through allocation of all direct costs for specific
      processes in a given institution. Indirect costs are settled on the basis of
      resources used during the implementation of individual tasks involved in the
      process of making a new product. In this method, so called map of
      processes/actions consisted in the manufactured product and their interrelations
      are of particular importance. Advancements in the cost-effect for the management
      of health care institutions depend on their managerial needs. Current trends in
      this regard primarily depend on treating all cost reference subjects as cost
      objects and taking account of all their interrelations. Final products, specific
      assignments, resources and activities may all be regarded as cost objects. The
      ABC method is characterized by a very high informative value in terms of setting
      prices of products in the area of workers' health care. It also facilitates the
      assessment of costs of individual activities under a multidisciplinary approach
      to health care and the setting costs of varied products. The ABC method provides
      precise data on the consumption of resources, such as human labor or various
      materials.

PMID- 17533996
TI  - Dying in pieces.

PMID- 17533997
TI  - Effectiveness of support groups for people with mild to moderate Alzheimer's
      disease: an evaluative survey.
AB  - Support groups can provide a forum for socialization and learning for people with
      mild to moderate Alzheimer's disease. The aim of this study was to evaluate the
      effectiveness of these groups based on participant feedback. A survey
      questionnaire was administered to 70 support group participants with Alzheimer's
      disease from 8 well-established groups across the United States. Participants
      reported on the educational value, positive socialization, and improved ability
      to cope with symptoms and to accept the diagnosis as a result of participating in
      a support group. These reported outcomes suggest the importance of creating more
      sensitive measures to better evaluate the effectiveness of support groups and
      other educational or social support programs for persons with dementia.

PMID- 17533998
TI  - Telehealth home monitoring of solitary persons with mild dementia.
AB  - Medication safety is a special concern for the 30% to 40% of dementia patients
      who live alone at the time of diagnosis, and it plays an important part in
      relocation decisions. Televideo monitoring could improve medication self
      administration accuracy and improve mood for persons with mild dementia who live
      alone or spend a significant amount of their day alone. The authors used 2-way
      interactive video technology to monitor medication compliance of 8 persons with
      mild dementia. They conducted more than 4000 contacts with these persons and
      found adequate technical outcome in 82% of calls. End medication compliance was
      81% in the video-monitored group compared to 66% in the controls (P < .05).
      Comparison of compliance from initial to end ratings revealed that video
      monitored participants' compliance remained stable while unmonitored patients'
      compliance fell 12 percentage points, consistent with expectations for dementia.
      This difference was also significant. Quantitative and qualitative outcome data
      from this project are presented.

PMID- 17533999
TI  - Resident-Assisted Montessori Programming (RAMP): use of a small group reading
      activity run by persons with dementia in adult day health care and long-term care
      settings.
AB  - Six persons in the early to middle stages of dementia ("leaders") were trained in
      Resident-Assisted Montessori Programming (RAMP) to lead a reading activity for 22
      persons with more advanced dementia ("participants") in an adult day health
      center (ADHC) and a special care unit (SCU) in a skilled nursing facility.
      Researchers assessed the leaders' abilities to learn and follow the procedures of
      leading a group, as well as their satisfaction with their roles. In addition,
      participants' engagement and affect were measured, both during standard
      activities programming and during client-led activities. Results of this study
      suggest that persons with dementia can indeed successfully lead small group
      activities, if several important prerequisites are met. Furthermore, the
      engagement and affect of participants was more positive in client-led activities
      than in standard activities programming.

PMID- 17534000
TI  - The genetics of Alzheimer's disease.
AB  - The genetics of Alzheimer's disease is produced by 3 essentially interactive gene
      groups: (1) APP and presenilin 1 and 2; (2) APOE E2, E3, and E4; (3) genes on
      chromosomes 9, 10, 12, etc. If any gene in (1) mutates, beta amyloid (Abeta)
      increases sharply beyond what the genes of (3) can remove, with early-onset
      Alzheimer's disease the result. With retention of Abeta by E4 in (2), Alzheimer's
      disease might result even though (1) and (3) are normal. If any gene in (3)
      mutates, the level of Abeta will rise, but because many genes are involved in
      Abeta removal, late-onset Alzheimer's disease would be detected only eventually.

PMID- 17534001
TI  - Cognitive and psychopathologic response to rivastigmine in dementia with Lewy
      bodies compared to Alzheimer's disease: a case control study.
AB  - Cholinesterase inhibitors (ChEIs) are effective in improving cognition and
      behavior in patients affected by Alzheimer's disease (AD) as well as by Lewy
      bodies dementia (DLB). The authors compared the effect of rivastigmine in the
      treatment of cognitive impairment and behavioral and psychological symptoms of
      dementia (BPSD) in 30 AD and in 30 DLB patients. At baseline, DLB compared to AD
      patients showed a greater number of extrapyramidal symptoms (P < .005) and were
      similar regarding cognitive symptoms and BPSD. After treatment, both groups
      showed a comparable cognitive and psycho-behavioral improvement. A significant
      difference between AD and DLB patients was found for hallucinations (P < .002).
      Rivastigmine produces comparable cognitive benefits in patients with DLB and AD
      and also a significant improvement of behavioral disorders. These findings
      support the view that ChEIs should be considered a first-line treatment of the
      cognitive and psycho-behavioral symptoms of both AD and DLB.

PMID- 17534002
TI  - Course and causes of suspected dementia in young adults: a longitudinal study.
AB  - The authors performed a prospective, unbiased analysis of a cohort of young
      patients assessed consecutively with the question of dementia. The onset of
      patients' cognitive symptoms was prior to the age of 65 years. A study group of
      226 patients was followed for a mean duration of 4.59 +/- 2.23 years (1 SD;
      range, 0.04-7.86 years). The diagnoses were established using published
      diagnostic criteria. A diagnosis of dementia was made in 112 patients (49.56%).
      Psychiatric disease was the most common diagnosis in those who did not have
      dementia (24.3%) followed by frontotemporal lobar degeneration (19.0%),
      Alzheimer's disease (11.9%), patients with cognitive symptoms who obtained normal
      neuropsychometric profiles (10.6%), nonneurological disorders (eg, obstructive
      sleep apnea [8.4%]), neurological disorders (eg, Parkinson's disease [4.9%]), and
      mild cognitive impairment (4.9%). The frequencies of frontotemporal lobar
      degeneration and psychiatric disease were higher than Alzheimer's disease, unlike
      in older populations.

PMID- 17534003
TI  - The influence of beta-blockers on delayed memory function in people with
      cognitive impairment.
AB  - Adrenergic signaling is important for the retrieval of intermediate-term
      contextual and spatial memories. The role of norepinephrine in retrieval requires
      signaling through beta1-adrenergic receptors in the hippocampus. Environmental
      cues activate the locus ceruleus, the main adrenergic nucleus of the brain, when
      an environmental stimulus is memorable. This leads to norepinephrine activation
      in the hippocampus, which is important for retrieving memories. Although beta
      blockers do not impair cognition in normal subjects, this article explores the
      possibility that central nervous system (CNS)-active beta-blockers could affect
      delayed memory in patients with cognitive impairment. The authors investigated
      the influence of beta-blockers on delayed memory function in cognitively impaired
      patients. There was a trend for worse delayed memory retrieval in patients who
      were on CNS-active beta-blockers. These data support the notion that common
      medications used in cognitively impaired elderly patients can worsen cognition
      and that careful selection of medications may help to maximize retrieval of newly
      formed memories.

PMID- 17534004
TI  - Language-enriched exercise plus socialization slows cognitive decline in
      Alzheimer's disease.
AB  - This article reports the effects of language-enriched physical fitness
      interventions provided by University of Arizona undergraduate students to 24 mild
      to moderate-stage Alzheimer's disease patients (AD Rehab group). Socialization
      experiences consisted of supervised volunteer work and cultural/recreational
      activities. Changes in global functioning and neuropsychological test performance
      were tracked and compared to those of a similar group of untreated patients from
      the Consortium for the Establishment of a Registry for Alzheimer's Disease
      (CERAD). Cohorts completing 4 semesters or longer showed no significant between
      year changes after their first year on the Clinical Dementia Rating, a measure of
      global functioning, and on 5 or 6 of the cognitive and language measures.
      Comparisons with the CERAD sample suggested a slower rate of decline for the AD
      Rehab group. The stabilization of global and cognitive performance was not
      apparent among participants who completed only 2 semesters. Significant physical
      fitness and mood outcomes were previously reported in this journal.

PMID- 17534005
TI  - Elective and isolated carotid endarterectomy: health disparities in utilization
      and outcomes, but not readmission.
AB  - BACKGROUND: Carotid endarterectomy (CEA) has been shown to decrease future
      ischemic stroke risk in selected patients. However, clinical trials did not
      examine the risk-benefit ratio for nonwhites, who have a greater ischemic stroke
      risk than whites. In general, few studies have examined the effects of race on
      CEA use and complications, and data on race and CEA readmission are lacking.
      METHODS: This study used administrative data for patients discharged from
      California hospitals between January 1 and December 31, 2000. Selection criteria
      of cases included: ICD-9 principal procedure code 38.12, principal diagnostic
      code 433 and diagnosis-related group 5. There were 8,080 white and 1196 nonwhite
      patients (228 blacks, 643 Hispanics, 325 Asians/Pacific Islanders) identified
      that underwent an elective and isolated CEA. For both groups, CEA rates were
      compared. Logistic regression was used to examine the independent effects of race
      on in-hospital death and stroke, as well as CEA readmission. RESULTS: Rates of
      CEA use were more than three times greater for whites than nonwhites, although
      nonwhites were more likely to have symptomatic disease. For all patients, the
      complication rate was 1.9%. However, the odds of in-hospital death and stroke
      were greater for nonwhites than whites, but after adjustment for patient and
      hospital factors, these differences were only significant for stroke (OR = 1.7, P
      = 0.013). For both outcomes, the final models had good predictive accuracy.
      Overall, CEA readmission risk was 7%, and no significant racial differences were
      observed (P = 0.110). CONCLUSIONS: The data suggest that CEA is performed safely
      in California. However, nonwhites had lower rates of initial CEA use but higher
      rates of in-hospital death and stroke than whites. Racial differences in stroke
      risk persisted after adjustment for patient and hospital factors. Finally, this
      study found that despite significant racial disparities in initial CEA use,
      whites and nonwhites were similar in their CEA readmission rates. These findings
      may suggest that screening initiatives are lacking for nonwhites, which may
      increase their risk for poorer outcomes.

PMID- 17534006
TI  - Relationships and communication in minority participation in research:
      multidimensional and multidirectional.
AB  - We examined the range and nature of investigators' communication and relationship
      building as they recruit minority participants in their research. Semistructured,
      in-depth interviews were conducted with 33 investigators conducting research with
      human participants. The response rate was 77%. Investigators described several
      kinds of relationships that are formed or called upon when including minority
      participants in research. The relationships ranged from study-related, short-term
      interactions geared solely to facilitate recruitment to others that were longer
      term, extending beyond a particular project. The data suggest that a range of
      relationships is important as investigators seek to include minority populations
      in research. These relationships can both facilitate the recruitment process as
      well as aid in the interpretation of research findings.

PMID- 17534007
TI  - Increasing incidence of clostridium difficile-associated diarrhea in African
      American and Hispanic patients: association with the use of proton pump inhibitor
      therapy.
AB  - BACKGROUND: Clostridium difficile-associated diarrhea (CDAD) has been
      increasingly diagnosed in hospitalized patients. The number of prescriptions for
      proton pump inhibitors (PPIs) has also increased significantly over time. Few
      studies have reported an association between CDAD and PPI use; however, the
      results are inconclusive. OBJECTIVE: To determine the relationship between CDAD
      and PPI use in African-American and Hispanic patients. METHODS: We
      retrospectively reviewed medical records of 640 cases with CDAD over nine years,
      diagnosed by the presence of C. difficile toxin in the stools. Age-/ sex-matched
      650 patients with diarrhea but absent C. difficile toxin in stools were used as
      controls. RESULTS: Of the 640 cases, 576 (90%) received antibiotics and 32 (5%)
      received chemotherapy during the preceding three months. Of the 650 controls, 540
      (83%) received antibiotics and 39 (6%) received chemotherapy during the preceding
      three months. CDAD was associated with the use of antibiotics or chemotherapy (OR
      = 2.3, 95% CI: 1.5-3.7). Of the 608 cases receiving antibiotics or chemotherapy,
      274 (45%) also received PPI within the preceding three months. Of the 579
      controls who received antibiotics or chemotherapy, 169 (29%) also received PPI
      within preceding three months. CDAD was associated with the use of PPI (OR = 2.0,
      95% CI: 1.6-2.6). CONCLUSION: Our findings indicate that PPI may be an emerging
      and potentially modifiable risk factor for CDAD and point out the importance of
      vigilance in prescribing PPI, particularly to patients who are hospitalized,
      taking multiple antibiotics and suffering from multiple comorbidities.

PMID- 17534008
TI  - Association between past urinary tract infections and current symptoms suggestive
      of chronic prostatitis/chronic pelvic pain syndrome.
AB  - Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a major cause of
      illness, and its association with history of past urinary tract infections is
      unclear. We surveyed a racially, ethnically and socioeconomically diverse,
      community-based sample of adults aged 30-79 years in Boston, MA. This report
      gives estimates from the 2,301 men in the BACH survey: 700 black, 766 Hispanic
      and 835 white. Symptoms of chronic prostatitis--any perineal and/or ejaculatory
      pain and a pain score of > or =4--were derived from the NIH Chronic Prostatitis
      Symptom Index and were used to identify men with symptoms suggesting CP/CPPS. The
      overall prevalence of symptoms suggestive of CP/CPPS is 6.3%. The number of
      urinary tract infections, particularly >3, was associated with symptoms
      suggestive of CP/CPPS (P < 0.01). There is a strong association between current
      symptoms of CP/CPPS and a history of urinary tract infections, particularly of
      multiple infections. The causality between chronic UTIs and CP/CPPS needs to be
      clarified by further study.

PMID- 17534009
TI  - Dynamic association between parental monitoring and communication and adolescent
      risk involvement among African-American adolescents.
AB  - PURPOSE: To examine: (1) the relationship between parental monitoring and
      communication and adolescent risk involvement over time, including consideration
      of their potential interaction; and (2) the effect of consistent versus
      inconsistent monitoring and communication over time on adolescent risk behaviors.
      METHODS: Baseline and follow-up data were collected from 1999-2003. A total of
      817 African-American adolescents and their parents were recruited from 35 low
      income urban communities in Baltimore, MD. Perceived parental monitoring, parent
      adolescent communication and seven risk behaviors were assessed. Logistic general
      estimating equation (GEE) models were performed to assess the dynamic
      association. RESULTS: Perceived parental monitoring had protective effects on
      concurrent adolescent risk involvement over two-year observation. The protective
      effect on girls' sexual abstinence increased significantly over time. Perceived
      problem communication was associated with increased risk of concurrent
      involvement in violent behaviors, but the effect did not change over time. For
      girls, the probability of engaging in sex increased greatly (from 0.3 to 0.6) for
      those who perceived problem communication, while it remained stable (about 0.4)
      for those perceiving less problem communication. CONCLUSIONS: The data confirm
      the protective effect of perceived parental monitoring on adolescent risk
      involvement. It also extends previous findings by showing the importance of
      consistent parental monitoring and communication.

PMID- 17534010
TI  - Colon cancer screening consultations may identify racial disparity in
      hypertension diagnosis and management.
AB  - There are significant health disparities between African Americans and whites in
      the United States. While colon cancer screening aids in decreasing the morbidity
      and mortality from colon cancer in African Americans, other health risks may also
      be identified during gastroenterology consultations. This study evaluated whether
      there is a disparity in the prevalence of hypertension and hypertension
      management in African Americans compared to whites who are referred for colon
      cancer screening consultations. The medical records of 258 patients (90 African
      Americans and 168 whites) were reviewed. Seventy-two of 90 (80%) African-American
      patients and 42 of 168 (25%) white patients had hypertension. There was a
      statistically significant difference (p < 0.005) in the rate of hypertension in
      African Americans compared to whites. Medications were prescribed by their
      referring physicians for 42 (58%) of the hypertensive African Americans, with 36
      noted to have inadequately controlled blood pressure. Thirty (42%) of the
      hypertensive African-American patients were never prescribed blood pressure
      medications. Medications were prescribed by their referring physician for 36
      (86%) of the hypertensive white patients, with six noted to have inadequately
      controlled blood pressure. Six (14%) of the hypertensive white patients were
      never prescribed blood pressure medications. There was a statistically
      significant difference in the rate of blood pressure control (p = 0.007) between
      African-American and white patients who were referred for colon cancer screening.
      Increased efforts are necessary to identify critical health concerns of all
      patients and to decrease health disparities between African Americans and whites
      in the United States.

PMID- 17534012
TI  - Cancer screening participation: comparative willingness of San Juan Puerto Ricans
      versus New York City Puerto Ricans.
AB  - OBJECTIVES: The specific aim of this study was to determine the self-reported
      likelihood of New York Puerto Ricans (NYPR) and San Juan Puerto Ricans (SJPR) to
      participate in: 10 site-specific cancer screenings, cancer-screenings conducted
      by different specific persons/agencies and cancer-screening under specific
      conditions of what one was asked to do as a part of cancer screening. METHODS:
      The Cancer Screening Questionnaire (CSQ) was administered via random-digit-dial
      telephone interviews to 154 adults living in San Juan, PR and 155 in New York,
      NY. RESULTS: Although the self-reported willingness to participate across the 10
      site-specific cancer screening exams was consistently high in both cities, SJPR
      had higher rates, as compared to NYPR for all 10 site-specific cancer screening
      exams in the unadjusted analyses. A similar pattern was observed regarding the
      influence of both "who conducts the cancer-screening exam" and "what one is asked
      to do in a cancer-screening exam" as factors in the willingness to participate in
      such exams. Adjusted multivariate analysis showed that the odds of SJPR
      participating in skin cancer screening as compared to NYPR, were three-fold
      higher to participate in skin cancer screening and were two-fold higher to
      participate in a cancer screening where they have to be interviewed about their
      alcohol habits. These two observed differences might reflect the effect of
      acculturation in the NYPR.

PMID- 17534011
TI  - When race matters: disagreement in pain perception between patients and their
      physicians in primary care.
AB  - Patients and physicians often disagree in their assessment of pain intensity.
      This study explores the impact of patient factors on underestimation of pain
      intensity in chronic noncancer pain. We surveyed patients and their physicians in
      12 primary care centers. To measure pain intensity, patients completed an 11
      point numeric rating scale for which pain scores range from 0 (no pain) to 10
      (unbearable pain). Physicians rated patients' pain on the same scale. We defined
      disagreement of pain intensity as underestimation or overestimation by 22 points.
      Of 601 patients approached, 463 (77%) completed the survey. The majority of
      participants were black (39%) or white (47%), 67% were female, and the mean age
      was 53 years. Physicians underestimated pain intensity relative to their patients
      39% of the time. Forty-six percent agreed with their patients' pain perception,
      and 15% of physicians overestimated their patients' pain levels by > or =2
      points. In both the bivariate and multivariable models, black race was a
      significant variable associated with underestimation of pain by physicians (p <
      0.05; OR = 1.92; 95% CI: 1.31-2.81). This study finds that physicians are twice
      as likely to underestimate pain in blacks patients compared to all other
      ethnicities combined. A qualitative study exploring why physicians rate blacks
      patients' pain low is warranted.

PMID- 17534013
TI  - Understanding "masculinity" and the challenges of managing type-2 diabetes among
      African-American men.
AB  - African-American men bear a greater burden of type-2 diabetes and its associated
      complications. The purpose of this analysis was to explore in greater depth
      themes that emerged in illness narratives of a small sample of African-American
      men living with type-2 diabetes. The primary theme that is the focus of this
      article is the lived experience of black manhood and masculinity and its
      intersection with the challenges of diabetes self-management. In-depth interviews
      with 16 African-American men who had established type-2 diabetes yielded thematic
      analyses of four questions: (1) What do you fear most about having diabetes? (2)
      In what ways have people in your life treated you differently after learning you
      have diabetes? (3) In what ways has knowing you have diabetes affected the way
      you see yourself? and (4) What are some reactions when you tell people you have
      diabetes? This preliminary study suggests that the requirements of diabetes self
      management often run counter to the traditional sex roles and learned behaviors
      of African-American men, and this can contribute to nonadherence to medications
      and poor glycemic control. Gender identity is a key cultural factor that
      influences health-related behaviors, including how men with type-2 diabetes
      engage with the healthcare system and manage their diabetes. Understanding
      African-American men's gender identity is an important component of cultural
      competency for physicians and can be consequential in patient outcomes.

PMID- 17534014
TI  - Inherited, familial and sporadic primary open-angle glaucoma.
AB  - The U.S. surgeon general has recently launched a campaign to promote the
      awareness of the medical value of family history. Further attention should be
      paid to familial aggregation. Accordingly, we suggest that primary open-angle
      glaucoma (POAG) be classified into inherited, familial and sporadic categories.
      The three classes of POAG differ not only in inheritance pattern and familial
      aggregation but also in methodology and outcome of gene mapping. Inherited POAG
      follows Mendelian inheritance and has been linked to seven chromosomal loci to
      date by linkage analysis. Familial POAG does not show a clear pattern of
      Mendelian inheritance and is typically studied by sib-pair analysis and family
      based association analysis, although the results often require replication in
      multiple samples. Interestingly, many sporadic POAG cases carry known POAG
      causing mutations, suggesting genetic predisposition as well. Based on published
      data, we estimated that inherited and familial POAG cases may account for
      approximately 72% of all POAG cases. We further formulated a mathematic model to
      estimate disease prevalence and mutation frequency taking both ethnic background
      and familial aggregation into consideration. CONCLUSION: POAG appears to be
      mainly caused by genetic predisposition in interaction with other risk factors
      such as age. The suggested classification of POAG may serve as a useful guide in
      clinical practice and genetic studies where ethnic background and familial
      aggregation must be taken into consideration.

PMID- 17534015
TI  - Ethnicity, alcohol drinking and changes in transaminase activity among heavy
      drinkers.
AB  - BACKGROUND: Liver cirrhosis mortality differs by ethnicity in the United States.
      Some studies suggest alcohol sensitivity may contribute to this finding. This
      analysis evaluated if alcohol-associated changes in aspartate aminotransferase
      (AST) and alanine transaminase (ALT) differed by ethnicity among heavy drinkers.
      METHODS: Subjects included 1691 subjects from Project MATCH, a multicenter
      alcohol use disorders treatment trial. Changes in AST and ALT over 15 months were
      modeled as functions of ethnicity, age, gender, time, study site and alcohol use.
      The main focus was on ethnic differences in changes in transaminase activity
      occurring with changes in alcohol use. RESULTS: At all levels of alcohol
      consumption AST was lower in non-Hispanic whites relative to African Americans
      and Mexican Americans. Changes in AST associated with changes in alcohol use did
      not vary by ethnicity. ALT significantly differed only between Mexican Americans
      and non-Hispanic whites. Similar to AST, alcohol-associated ALT change did not
      differ by ethnicity. CONCLUSIONS: Among individuals with alcohol use disorders
      participating in a treatment trial, the effect of alcohol drinking on
      transaminase activity did not vary by ethnicity. However, in the general
      population, alcohol may still interact with other factors in mediating ethnic
      differences in cirrhosis mortality.

PMID- 17534017
TI  - Micronodular radiographic pulmonary pattern in metastatic medullary thyroid
      carcinoma.
AB  - Medullary carcinoma of the thyroid is a rare form of all thyroid malignancies,
      thereby limiting the clinical nature and the ability to optimize diagnostic
      tools. We present two cases of a micronodular radiographic pulmonary pattern in
      metastatic medullary thyroid cancer to enhance awareness of the disease process.
      We reviewed the literature to examine the ideal methods to establish a diagnosis.

PMID- 17534016
TI  - Surgical pathology of schistosomiasis.
AB  - Schistosomiasis remains an important health problem in many tropical countries
      and is being seen with increasing frequency in immigrant populations and tourists
      in developed countries. The pattern of organ involvement and clinical
      presentation of schistosomiasis in 80 patients (male: female, 9:1) during a five
      year period (2001-2005) was examined from archival histopathology records. The
      urinary bladder was the most common organ affected [50 (62.5%)].
      Gastrointestinal, male and female genital schistosomiasis were detected in 12
      (15%), eight (10%) and five (6.1%) cases, respectively. Hematuria was the most
      common presenting symptom [34 (42.5%)], and bladder cancer was the only
      malignancy found to be associated with the infection. A high clinical index of
      suspicion usually allows for a preoperative diagnosis where indicated and
      avoidance of radical surgery. While research for the development of an effective
      vaccine continues, a plea is made for the expansion of multinational control
      programs in sub-Saharan Africa.

PMID- 17534018
TI  - Charity Hospital: from the beginning to either a new beginning or the end.
AB  - Through epidemics, wars, hurricanes, pirates and politics, Charity Hospital has
      served the indigent population of New Orleans and Louisiana since May 10, 1736 as
      the second oldest continuing public hospital in the country following Bellevue in
      New York City, which opened six weeks earlier on March 31, 1736. The first
      Charity facility was financed by the estate of boat builder Jean Louis, whose
      will recorded, "a sale shall be made of all that remains, which, together with my
      small lot, I bequeath to serve in perpetuity to the founding of a hospital for
      the sick of the City of New Orleans...".

PMID- 17534019
TI  - The future of New Orleans' Charity Hospital.

PMID- 17534020
TI  - Charity Hospital: a former Tulane dean's perspective.

PMID- 17534021
TI  - What is the difference between a Charity Hospital system and a university
      hospital system?

PMID- 17534022
TI  - The Charity Hospital dilemma.

PMID- 17534023
TI  - If not Charity Hospital, then an equivalent facility is imperative.

PMID- 17534024
TI  - Rebuild Charity Hospital as a new entity.

PMID- 17534025
TI  - Salvaging a geriatric medicine academic program in disaster mode-the LSU training
      program post-Katrina.
AB  - Formal training in geriatric medicine in Louisiana is in its infancy. This
      article portrays the struggle of the sole functioning geriatric medicine training
      program and its trials and tribulations in a survival mode, opportunities that
      come with disaster as well as lessons learned post-Katrina.

PMID- 17534026
TI  - [Professor Dr. Med. Walther Graumann (1915-2006)].

PMID- 17534027
TI  - [Is anatomy still an art?].

PMID- 17534028
TI  - Neuron-specific Hu proteins sub-cellular localization in primary sensory neurons.
AB  - The Hu family of RNA-binding proteins is involved in many post-transcriptional
      mechanisms for the development and maintenance of the nervous system. Three
      members of the Hu family (HuB, HuC and HuD) are neuron-specific proteins. In this
      study, we present data using light and electron microscopy to show the sub
      cellular localization of neuron-specific Hu proteins in rat primary sensory
      neurons taken from dorsal root ganglia (DRG). Using these techniques we
      morphologically revealed the presence of neuron-specific-Hu proteins in the
      nucleus and in the cytoplasm and discriminated the presence of Hu proteins within
      different cellular organelles, specifically mitochondria and Golgi apparatus,
      thus supporting previous ideas that NS-Hu proteins enable RNA interactions with
      sub-cellular organelles and may be involved in mRNA cellular localization.

PMID- 17534029
TI  - Secondary palatal closure in rats in association with relative maternofetal
      levels of folic acid, vitamin B12, and homocysteine.
AB  - Animal experiments are used in embryological and teratological studies of matters
      relevant to humans. In gravid rats, a decrease in the levels of folic acid and
      vitamin B12 was observed in maternal blood and in amniotic fluid. At the time of
      secondary palatal closure (14th day of pregnancy), the folic acid level of the
      amniotic fluid was 73% lower than that of the maternal blood. A drop in vitamin
      B12 in conjunction with an increase in amniotic homocysteine levels is seen as a
      risk factor for malformation of the palate. The understanding of causes of cleft
      generation could lead to a prophylactic treatment approach.

PMID- 17534030
TI  - Wedge cells during regeneration of juvenile and adult feathers and their role in
      carving out the branching pattern of barbs.
AB  - The present ultrastructural study on regenerating feathers emphasizes the role of
      supportive cells in determining the branching pattern of barbs. Supportive cells
      are localized among developing barb and barbule cells, in marginal plates, and
      underneath the feather sheath, and their differentiative fate, in general, is a
      form of lipid degeneration. The Latter process determines the carving out of barb
      branching in both downfeathers and pennaceous feathers. In the latter feathers,
      some supportive cells (barb vane cells and cylindrical cells of marginal plates)
      degenerate within each barb ridge leaving separate barbules. Other supportive
      cells, here termed wedge cells, form columns of cornified material that merge
      into elongated corneous scaffolds localized among barbs and the rachis. This
      previously undescribed form of cornification of supportive cells derives from the
      aggregation of periderm and dense granules present in wedge cells. The latter
      cells give origin to a corneous material different from feather keratin that may
      initially sustain the early and soft barbules. After barbules are cornified the
      supportive cells scaffolds are eventually sloughed as the sheath breaks allowing
      the new feather to open up and form a planar vane. The corneous material of wedge
      cells may also contribute to molding of the overlapped nodes of barbule cells
      that form lateral spines or hooklets in mature barbules. Eventually, the
      disappearance of wedge cell scaffolding determines the regular spacing of barbs
      attached to the rachis in order to form a close vane.

PMID- 17534031
TI  - Insular dentin formation pattern in human odontogenesis in relation to the
      scalloped dentino-enamel junction.
AB  - This study is a first report on the modality of early dentin formation in respect
      to the scalloped pattern of the dentino-enamel junction (DEJ). We applied
      scanning electron microscopy (SEM), transmission electron microscopy (TEM),
      histological serial sections, and three-dimensional (3D) reconstructions. TEM and
      SEM showed scallops and secondary scallops on the DEJ of deciduous dental
      primordia and on deciduous teeth with the enamel cap removed. This peculiar
      outline of the DEJ requires a specific dentin formation pattern; histological
      sections showed that dentin formation began at the brims of the scallops, seen as
      triangular spikes in serial sections. The dentin formation front was not uniform;
      instead, it was characterized by multiple, insular forming centers, as revealed
      by our 3D reconstructions. As thicker dentin layers formed, the islands became
      confluent. Factors are discussed, which may lead to crimpling of the inner enamel
      epithelium, and maintained as the scalloped pattern of the DEJ develops.
      Signaling patterns in accordance with the insular dentin formation are unknown so
      far.

PMID- 17534032
TI  - [Integration of a seminar on the anatomical basis of otorhinolaryngology (ENT)
      into the clinical course improves the confidence and performance of students in
      the clinical discipline].
AB  - A sound knowledge of the scientific basis of medicine is a prerequisite for
      successful learning and understanding of clinical issues. Teachers of clinical
      medicine, however, often complain that their students' knowledge on the
      scientific basis of medicine is too low. In the clinical curricula of most
      medical schools in Germany, students rely on self-directed learning efforts to
      optimize their knowledge of basic issues for the study of clinical medicine.
      Using anatomy and otorhinolaryngology (ENT) as an example, we have compared the
      effects of a structured seminar for recall of anatomical knowledge and its
      elaboration under clinical perspective with self-directed learning efforts of the
      same contents. Effects on clinical performance and students confidence were
      compared in a randomized trial. We found that the clinical performance of
      students was significantly higher (6.9%) in the seminar group compared with the
      control group. Furthermore, the students' self-estimation of clinical competence
      was increased in the seminar group and they were more content with their clinical
      course in ENT. Based on the design of the study we believe that the improvement
      of clinical performance was a longterm effect due to deeper understanding of the
      clinical problems among participants of the seminar. Irrespective of their
      experimental study group, most students asked for more integration of seminars on
      the scientific basis of medicine into the clinical curriculum. With the
      significant increase in clinical performance shown in this study and the limited
      effort needed for implementation, these seminars could be an efficient way to
      improve the quality of teaching in clinical medicine.

PMID- 17534033
TI  - The three-dimensional architecture of the human styloglossus especially its
      posterior muscle bundles.
AB  - The arrangement of the lingual muscles in the interior of the human tongue,
      particularly the course of the posterior muscle bundles of the styloglossus, was
      studied by gross anatomical examination and SEM, and its relationship with tongue
      functions was considered. The styloglossus divided into anterior and posterior
      fiber bundles. The bilateral anterior fiber bundles ran anteriorly, and fused at
      the median region of the lower surface of the tongue, forming a large arched
      structure. The posterior bundles divided into 10 or more smaller bundles and
      entered the interior of the tongue. These muscle bundles passed through the
      spaces between the inferior longitudinal and genioglossus and inserted in the
      lingual septum, forming a small arched structure. These posterior muscle bundles
      passed near the midpoint between the central third and dorsal third of the line
      between the mental spine and the dorsal surface of the tongue in the upper half
      of the root of the tongue, showing a multilayer structure. In many of the areas
      in which posterior muscle bundles were distributed, muscle bundles in the tongue
      were arranged along the posterior muscle bundles of the styloglossus,
      glossopharyngeal bundles of the superior pharyngeal constrictor muscle, and
      transverse muscle of the tongue from the deep layer to the dorsal surface of the
      tongue.

PMID- 17534034
TI  - Histological and histomorphometric investigation of the condylar cartilage of
      juvenile pigs after anterior mandibular displacement.
AB  - The condylar cartilage of the mandible is considered a secondary growth center
      and represents a joint cartilage different from other cartilage structures
      regarding its histological structure, its histochemical and immunohistochemical
      properties and its growth pattern. This study aimed to histologically and
      histomorphometrically investigate the condylar cartilage after anterior
      mandibular displacement similar to functional orthopedic treatment. A total of 12
      pigs (sus scrofa domesticus) aged 10 weeks were divided into an experimental
      group and a control group comprising 6 animals each. The experimental animals
      were provided bilaterally with synthetic occlusal build-ups in the posterior area
      which induced anterior displacement of the mandible in terminal occlusion. After
      4 weeks, the temporomandibular structures were removed en bloc and the condylar
      cartilage was analyzed histologically and histomorphometrically. As a result, the
      experimental animals displayed a significantly increased total cartilage
      thickness of the posterocranial mandibular condyle which was primarily caused by
      an increase in thickness of the hypertrophic and chondogenic layers. Similarly,
      the proliferative layer showed a significant increase, whereas significant
      differences in thickness were absent in the articular layer. Increased cell
      proliferation was not observed in the experimental animals as compared to the
      controls. The changes found in the condylar cartilage area suggest that the zonal
      structure of the condylar cartilage may be modified by an altered spatial
      relationship between the mandibular condyle and the glenoid fossa.

PMID- 17534035
TI  - Undescribed variant muscle--"deep abductor-flexor" of the little finger, in
      relation to ulnar nerve compression at the wrist.
AB  - During routine anatomical dissection in the hypothenar region of the left hand of
      a 64-year-old female cadaver, a number of variant structures were observed. The
      most prominent finding in our case was a supernumerary muscle hitherto unknown in
      the anatomical literature. This variant muscle had a muscular body formed by the
      connection of two deeply situated muscular bellies--medial and lateral. The
      lateral belly originated from the flexor retinaculum, the medial one--from the
      hamate bone. The common muscular body inserted to the antero-lateral surface of
      the base of the fifth proximal phalanx. Due to its location and possible
      function, we named the variant muscle "deep abductor-flexor" of the little
      finger. The flexor digiti minimi brevis muscle showed two proximal tendons--the
      medial tendon was attached to the hamulus of the hamate bone while the aberrant
      lateral tendon originated from the lateral part of the flexor retinaculum. Both,
      the aberrant lateral tendon of the flexor digiti minimi brevis and the lateral
      belly of the "deep abductor-flexor", passed over the palmar branch of the ulnar
      nerve, which define their possible clinical significance in ulnar nerve
      compression. Therefore, the variations of the hypothenar muscles are reviewed and
      their relation to the compression of the ulnar nerve is discussed.

PMID- 17534037
TI  - A rare variation of the right middle suprarenal artery.
AB  - According to general knowledge, the suprarenal gland is supplied by three
      sources: the phrenic artery, the abdominal aorta and the renal artery. Since the
      gland lacks a hilus, and particularly because of its clinical importance,
      anatomical arterial sources and branching is still not uniform and it needs to be
      determined by detail. In this study, the right middle suprarenal artery arising
      from the right renal artery was observed on the right side of a 45-year-old male
      cadaver.

PMID- 17534036
TI  - An additional radial wrist extensor and its clinical significance.
AB  - The knowledge of anatomical variations in the antebrachial and dorsal regions of
      the arm and hand are useful in hand surgery. The extensor carpi radialis
      intermedius and extensor carpi radialis accessorius are two classic variants
      described for the radial wrist extensors, in the antebrachial region. We report
      an additional extensor carpi radialis muscle taking origin from the common
      extensor origin, between the extensor carpi radialis longus and extensor
      digitorum communis. The tendon of the variant muscle divides below the abductor
      pollicis longus and becomes attached to the base of the second and third
      metacarpal bone. Due to its considerable size and independent origin from the
      lateral epicondyle, we suggest the present variation should be named extensor
      carpi radialis tertius. The clinical significance of the present variation is
      discussed.

PMID- 17534038
TI  - Bilateral arterial and nervous variations in the human upper limb: a case report.
AB  - During routine dissection, we found bilateral arterial and nervous anomalies in a
      female cadaver. On the left side the axillary artery divided into a medial
      brachial artery and lateral profunda brachii artery, and the musculocutaneous
      nerve arose from the upper trunk of the brachial plexus, before the formation of
      the lateral cord. On the right side a common trunk that divided into the
      circumflex scapular artery, thoracodorsal artery and posterior circumflex humeral
      artery was observed, while the musculocutaneous nerve fused with the median
      nerve.

PMID- 17534039
TI  - Distribution of the internal pudendal artery in male and female llama (Lama
      glama).
AB  - The aim of this research has been to describe the internal pudendal artery
      distribution in male and female llama and to compare it with that of other
      domestic animals including the one-humped camel (Camelus dromedarius). The
      arterial system was perfused with a solution of 14% coloured plaster and
      preserved in a solution of a 10% formalin, 3% carbolic acid and 3% glycerine. The
      systematic dissection was made using traditional working techniques and standard
      instruments. The internal pudendal artery is the ventral terminal branch of the
      internal iliac artery at the level of the third sacral vertebra. The main supply
      of the pelvic organs comes from the prostatic or vaginal arteries;
      notwithstanding these arteries arise from the internal pudendal artery, showing
      an important difference between ruminants and pig (long iliac type). Similarities
      between the distribution of the internal pudendal artery of the llama and those
      obtained in the camel provide strong evidence of a common phylogenetic origin.

PMID- 17534040
TI  - The complex arrangement of an "aorto-jejunal paraduodenal" fossa, as revealed by
      dissection of human posterior parietal peritoneum.
AB  - Peritoneal fossae derive from normal or anomalous coalescence of the peritoneum
      during fetal development, or from the course of retroperitoneal vessels.
      Clinically, internal abdominal hernias may be housed inside these fossae. In this
      report from an autopsy, a singular peritoneal fossa was delimited superiorly by
      an arcuate serous fold, raised up by the inferior mesenteric vein, and infero
      posteriorly by two (right and left) avascular folds, extending from the abdominal
      aorta to the jejunum. The right fold reached the duodeno-jejunal flexure, which
      was located on the right side of the aorta. The left fold subdivided into two,
      anterior and posterior, secondary folds. The anterior fold reached the superior
      edge of the first jejunal loop, and the posterior fold turned medially to connect
      with the inferior edge of the proximal limb of the same loop. This fossa
      consisted of three recesses: superior, Located behind the subserous vascular
      arch, antero-inferior and postero-inferior, separated by interposition of the
      left posterior secondary fold, between the jejunum and aorta. The complex
      arrangement of this fossa suggests that it might have originated from a
      coalescence arising beyond the duodeno-jejunal flexure and including the first
      jejunal loop, and from the subserous course of the inferior mesenteric vein.
      Because of displacement to the right of the flexure, processes of coalescence in
      a location normally occupied by the ascending duodenum might have occurred in a
      similar pattern for the jejunum, involving the mesoduodenum and the proximal part
      of the mesentery. Labyrinthine fossae like this might cause strangulation of
      internal abdominal hernias and hinder intraoperative maneuvers.

PMID- 17534041
TI  - Ritually induced growth disturbances and deformities of the orofacial system--a
      contribution to cranial morphogenesis.
AB  - Numerous ritual acts involving the skull result in orofacial changes. The present
      study focuses on ritual acts of Brazilian Zoe Indians. A distinct deformation
      effect of the ritual act (wearing a lip-plug) on the morphology of the orofacial
      system is demonstrated and documented using jaw models. The studies show that the
      lip-plug significantly influences tooth position and jaw growth. While the
      maxilla displays palatal displacement of the lateral incisors and elevation of
      the palate, retraction occurs in the mandible depending upon plug size.
      Additionally, both the plug and the nutritional habits of the Indians induce
      marked abrasion of all teeth. Moreover, it is shown that the duration of lip-plug
      wear is an essential determinant of sustained orofacial changes.

PMID- 17534042
TI  - Chronic rhinosinusitis patterns of illness.
AB  - Chronic rhinosinusitis is a complex, multifactorial illness that has genetic,
      infectious, immune, anatomic, allergic, and inflammatory components. The syndrome
      is defined based on imprecise symptoms that lack specificity for the condition.
      Nonetheless, certain relatively characteristic patterns of illness can be
      identified within the syndrome, and these provide some insight into the
      underlying cause(s) of CRS. Furthermore, they form a basis for the clinical
      assessment and management of patients. In general, CRS without NP is a more
      heterogeneous subgroup of patients more likely to have facial pain, headache,
      chronic recurrent infection, defects in systemic or local immune function, and
      more likely to experience local infectious complications, such as facial
      osteomyelitis. In contrast, CRS with NP patients are more likely to have male
      gender, anosmia/hyposmia, a history of prior sinus surgery, asthma and aspirin
      sensitivity, allergy to house dust mite, and AFRS. In the next 17 chapters, an in
      depth discussion of factors contributing to the pathophysiology of CRS will be
      presented that will provide further insight into the clinical patterns of illness
      described herein. Armed with this information plus the clinical framework
      outlined in this chapter, a stepwise medical evaluation and treatment strategy
      will be presented in Chapter 19.

PMID- 17534043
TI  - Impact of chronic rhinosinusitis on quality of life and health care expenditure.

PMID- 17534044
TI  - Environmental and allergic factors in chronic rhinosinusitis.

PMID- 17534045
TI  - Innate and acquired immunity and epithelial cell function in chronic
      rhinosinusitis.
AB  - We have outlined the myriad of roles, both proven and suspected, of epithelial
      cells in airway inflammation in general and CRS in particular. There is little
      doubt that these remarkable cells are essential for host defense, tissue
      responses to injury and threats, and inflammation that cause disease. We believe
      that many of these responses are likely to be amenable to the development of new
      therapies for CRS. As we acquire more information on the signaling processes that
      drive the protective responses in epithelial cells, we will improve our chances
      of developing approaches to enhance these responses without triggering
      deleterious inflammatory responses. Enhanced clearance of fungi and bacteria by
      local immune responses would likely be beneficial in reducing disease. As we
      better understand the signals that epithelial cells give and get from DCs, B and
      T lymphocytes, new opportunities for productive intervention will arise.

PMID- 17534046
TI  - Role of inflammatory T cells and eosinophils in chronic rhinosinusitis.

PMID- 17534047
TI  - Role of mast cells and basophils in chronic rhinosinusitis.
AB  - Mast cells and basophils contribute to induction and/or maintenance of
      eosinophilic inflammation by a variety of mechanisms, including IgE-dependent and
      IgE-independent processes. The latter include a variety of stimuli that have only
      recently been elucidated, including mechanisms triggered by bacteria, virus,
      fungi, complement, or autoantibodies. MCs, and basophils contribute to
      inflammation both directly through the release of inflammatory mediators,
      cytokines and growth factors and indirectly through the activation of structural
      cells. Accumulating evidence places MCs (and most probably basophils) in a
      position of importance in the pathogenesis of CRS, particularly in the
      pathogenesis and progression of NP (Fig. 1). Mechanisms other than conventional
      IgE-dependent activation of MCs are intriguing as potential mechanisms of
      eosinophilic inflammation in non-allergic CRS/NP. Although it is not possible
      using current pharmacologic approaches to completely isolate the effects of MCs
      or basophils in CRS and NP pathogenesis, it seems most likely that such
      approaches will eventually be available. It might be expected that one or both of
      these cells will be shown to play important roles, particularly considering their
      potential for activation by IgE and non-IgE mechanisms, their production of a
      broad array of inflammatory mediators, cytokines and growth factors, and their
      unique assortment of proteases.

PMID- 17534048
TI  - Mucociliary transport in chronic rhinosinusitis.
AB  - In conclusion, this chapter provides a review of paranasal sinus anatomy and
      discusses the physiology of mucociliary transport and abnormalities observed in
      patients with CRS. Normal mucociliary transport is essential for the maintenance
      of healthy sinuses. This is well illustrated by PCD in which a congenital
      abnormality in ciliary function leads to, among other manifestations, CRS and
      bronchiectasis. A decrease in mucociliary clearance has been demonstrated in most
      studies of CRS, with the bulk of evidence suggesting that the decrease is
      secondary rather than a primary event. Mucostasis, hypoxia, microbial products,
      and mediators and toxic proteins generated during chronic inflammation probably
      all contribute to diminished mucociliary function. These factors decrease
      mucociliary function by direct toxic effects on cilia, ciliary loss, other
      ultrastructural alterations in the epithelium and changes in the viscoelastic
      properties of mucus. Studies of patients before and after surgical restoration of
      sinus ventilation have shown that mucociliary function improves gradually over 1
      6 months postoperatively. The slower than normal rate of recovery of mucociliary
      clearance after surgery highlights the importance of careful postoperative
      medical and surgical management which is discussed in Chapters 19 and 20.

PMID- 17534049
TI  - Chronic rhinosinusitis with glandular hypertrophy.

PMID- 17534050
TI  - Bacterial infection and antibiotic treatment in chronic rhinosinusitis.
AB  - Incomplete resolution of acute rhinosinusitis leading to CRS is associated with a
      corresponding change in the microbiology of the disease. The shift in
      microbiology from acute to CRS favors infection with S. aureus, S. epidermidis,
      anaerobic bacteria (including beta-lactamase-producing strains), and gram
      negative bacteria. With the exception of S. epidermidis, there is substantial
      evidence supporting the role of these organisms in the pathogenesis of CRS. It is
      worth noting that not all CRS patients are chronically infected. In fact, other
      inflammatory factors in the disease may predominate in the clinical presentation.
      This creates a clinical conundrum in which it is difficult to ascertain whether
      bacteria are involved. In general, a chronic bacterial infection is more likely
      if there is: underlying immune deficiency, one or more opacified sinuses on sinus
      CT in the absence of polyps, the presence of frank purulence draining from one or
      more sinus cavities, or the presence of gram-negative or antibiotic-resistant
      organisms (e.g., MRSA) on sinus culture. For patients seen for the first time,
      the approach to antibiotic treatment is usually empiric, following the guidelines
      outlined in this chapter and directing treatment at both aerobic and anaerobic
      bacteria. Whenever possible, the choice of antibiotics should be guided by
      properly obtained sinus cultures. In cases where empiric antibiotics have failed,
      the need for bacterial cultures is even more critical to assure proper treatment
      and to minimize antibiotic side effects.

PMID- 17534051
TI  - Staphylococcus aureus enterotoxins as immune stimulants in chronic
      rhinosinusitis.

PMID- 17534052
TI  - The role of ubiquitous airborne fungi in chronic rhinosinusitis.

PMID- 17534053
TI  - Imaging of paranasal sinuses and rhinosinusitis.

PMID- 17534054
TI  - The role of nasal endoscopy in the diagnosis and medical management of chronic
      rhinosinusitis.

PMID- 17534055
TI  - Role of steroids in the treatment of rhinosinusitis with and without polyposis.

PMID- 17534056
TI  - Adjuvant therapies in the treatment of acute and chronic rhinosinusitis.

PMID- 17534057
TI  - Allergic fungal sinusitis.

PMID- 17534058
TI  - Medical management of rhinosinusitis comorbidities-asthma, aspirin sensitivity,
      gastroesophageal reflux, immune deficiencies.

PMID- 17534059
TI  - Chronic rhinosinusitis: contrasts between children and adult patients.

PMID- 17534060
TI  - Approach to the evaluation and medical management of chronic rhinosinusitis.
AB  - Despite the many frustrations involved in the care of CRS, there are many
      "successes," and most patients experience at least moderate benefit from medical
      treatment. I cannot emphasize enough the importance of breaking down the
      evaluation into component parts and addressing each one. Often, successful
      treatment is only achieved after all elements of the treatment program are in
      place. Patients are typically desperate for improvement and understand that
      several different strategies may need to be tried before a successful program is
      found. Given the high impact of CRS on patients' quality of life, it is not
      surprising that some of the most grateful patients are the ones in whom a
      successful medical program has been discovered.

PMID- 17534061
TI  - Interfacing medical and surgical management for chronic rhinosinusitis with and
      without nasal polyps.
AB  - The development of FESS provided the otolaryngologist with an approach for
      restoring sinus ostial patency while simultaneously maximizing the restoration of
      normal mucociliary function. While minor modifications to the basic procedure
      continue to be discussed, FESS is widely accepted as the standard of care for
      surgical management of CRS. Image-guided surgery offers further promise of
      allowing more precise surgery with fewer intraoperative complications. Most
      patients with CRS who fail medical therapy will benefit from FESS with improved
      outcomes and possibly improvement in comorbidities, especially asthma.
      Postoperative medical management and attention to contributive factors for
      disease, such as the presence of allergies and aspirin intolerance, are key
      factors toward assuring successful surgical outcomes. The surgical approach and
      outcomes vary somewhat based on whether the patient has CRS without NP, CRS with
      NP, or classic AFRS. Furthermore, the goals of surgery depend on whether other
      underlying conditions, such as cystic fibrosis, are present. The last section in
      this chapter provides guidance as to the combined medical and surgical management
      of various forms of CRS based on existing evidence from the literature.

PMID- 17534062
TI  - Transcriptional regulatory networks in macrophages.
AB  - The functions of macrophages in the innate immune system require the constitutive
      expression of a wide range of myeloid-specific genes, including various pattern
      recognition receptors, as well as the inducible expression of a suite of genes
      required to initiate inflammation and eliminate pathogens. Our overall aim is to
      understand the transcriptional networks that underlie both macrophage-specific
      transcription and the response to pathogen components such as lipopolysaccharide
      (LPS). The approaches used include detailed functional analysis of specific
      promoters, such as that of the CSF1 receptor, global cDNA microarray expression
      profiling, high throughput real-time PCR analysis of all the transcription
      factors encoded by the mammalian genome, full length cDNA library construction
      and sequencing, CAGE analysis to identify specific promoters used in macrophages
      and motif analysis to detect candidate cis-acting elements in co-regulated genes
      in macrophages. This review discusses some of the progress in moving towards a
      transcriptional network model for mouse macrophage activation by LPS, as well as
      insight into the role of alternative promoter usage and polyadenylation in
      generating functional protein variants that impact on signalling in macrophages.

PMID- 17534063
TI  - The RIKEN mouse transcriptome: lessons learned and implications for the
      regulation of immune reactions.
AB  - Notably, the technology and analysis methods of the RIKEN mouse full-length cDNA
      project have contributed a lot to the capture of the transcriptional output of
      the mouse genome and the description of its combinatorial nature. However, one
      corollary of this large scale transcript resource is the dichotomy of vast and
      missing information. As such, the transcriptional and translational output of yet
      unknown size following non-canonical principles remains to be established and
      interpreted. The importance of identifying immune-related transcripts and
      establishing their molecular functions in context of complex immune system
      diseases is clear: knowledge about the transcriptome can advance the
      understanding of immune system regulation. Decipher ing the logic of
      transcriptomes is critical for understanding the ontogeny and effector functions
      of immune cells, but it is not sufficient. The next challenge will lie in the
      combined sampling and integrated analysis of genomic elements, transcripts,
      proteins and metabolites.

PMID- 17534064
TI  - Molecular pathways for lymphangiogenesis and their role in human disease.
AB  - The lymphatic network functions to return fluid, cells and macromolecules to the
      circulation. Recent characterization of growth factors that control the growth
      and development of the lymphatics, and markers which specify lymphatic
      endothelial cells have enhanced our understanding of this system. Members of the
      VEGF family of factors are key regulators of these vessels with VEGF-C/VEGF-D and
      VEGFR-3 being the best validated signalling pathways in lymphangiogenesis. The
      study of these molecules in various pathologies has shown that they are important
      in the processes of cancer metastasis and in the formation of lymphoedema.
      Knowledge of these molecular pathways allows for the generation of modulators of
      these pathways which could form the basis of novel therapeutic approaches.

PMID- 17534065
TI  - Specifying the patterns of immune cell migration.
AB  - Immune system function depends on getting the right cells to the right place at
      the right time. Inadequate or inappropriate migration of immune cells is involved
      in many and perhaps all types of immunological disease. Chemokines have been
      identified as critical guidance factors that help recruit and position cells at
      each stage of the immune response. Two-photon imaging of intact lymphoid organs
      has provided evidence of chemotactic migration of lymphocytes in lymphoid organs.
      Our work on the role of chemokines as organizers of lymphoid tissues will be
      briefly summarized. Lymphocyte egress from lymphoid organs is necessary for
      immune surveillance and for effector cell trafficking to sites of inflammation.
      Sphingosine-1-phosphate (SIP) receptor 1 and the circulatory lipid, S1P, are
      required for lymphocyte egress from lymphoid organs. We have recently identified
      CD69 as a regulator of SIP1 and controller of lymphocyte egress. Current
      molecular understanding of the lymphocyte egress process will be discussed.

PMID- 17534066
TI  - Human monogenic disorders that confer predisposition to specific infections.
AB  - Human monogenic disorders affecting immunity to infection are increasingly
      recognized. Most are associated with primary immunodeficiencies, which typically
      confer predisposition to multiple infectious diseases. We review here the known,
      atypical monogenic disorders that confer a narrow vulnerability to infection with
      specific microorganisms in otherwise healthy individuals. These 'experiments of
      nature' have important immunological and clinical implications.

PMID- 17534067
TI  - The genetic control of susceptibility to Mycobacterium tuberculosis.
AB  - Mycobacterium tuberculosis is one of the most successful human pathogens, surviv
      ing in latent foci of infection in one third of humanity, yet causing lung
      necrosis in sufficient individuals to ensure its transmission. Each stage of the
      host response to M. tuberculosis is under genetic control, including the initial
      encounter with mycobacteria by macrophages, epithelial cells and dendritic cells
      in the lung, induction of the inductive T cell response, and killing by activated
      macrophages within granulomas. Although environmental factors are important
      determinants of progression to disease, there is a genetic component underlying
      susceptibility to tuberculosis (TB), the basis of which may vary in different
      populations. Recent studies using a variety of methods have defined a number of
      susceptibility alleles for the development of active TB. Many of these influence
      macrophage responses to mycobacteria. We have studied the influence of loss of
      function polymorphisms in the human P2X7 gene on the capacity of macrophages to
      kill M. tuberculosis. Activation of the P2X7 receptor, an ATP-gated Ca2+ channel,
      leads to the formation of pores, the activation of phospholipase D, and the
      induction of apoptosis with death of the infecting mycobacteria. Macrophages from
      subjects who are heterozygote, homozygote or compound heterozygote for these
      polymorphisms fail to undergo apoptosis and show partial or complete inhibition
      of mycobacterial killing. One of these non-functioning polymorphisms was
      significantly associated with increased susceptibility to TB disease,
      particularly extrapulmonary disease, in two unrelated cohorts of TB patients.
      Insights into the genetic regulation of susceptibility to human TB may identify
      novel methods for controlling latent M. tuberculosis and reducing the burden of
      tuberculosis.

PMID- 17534068
TI  - Th2 lymphoproliferative disorders resulting from defective LAT signalosomes.
AB  - LAT (linker for activation of T cells) is an integral membrane adaptor protein
      that constitutes in T cells a major substrate of the ZAP-70 protein tyrosine
      kinase. LAT coordinates the assembly of a multiprotein signalling complex through
      phosphotyrosine-based motifs present within its intracytoplasmic segment. The
      resulting 'LAT signalosome' links the TCR to the main intracellular signalling
      pathways that regulate T cell development and T cell function. Early studies
      using transformed T cell lines suggested that LAT acts primarily as a positive
      regulator of T cell receptor (TCR) signalling. The partial or complete inhibition
      of T cell development observed in several mouse lines harbouring mutant forms of
      LAT was congruent with that view. More recently, LAT 'knock-ins' harbouring point
      mutations in the four COOH-terminal tyrosine residues, were found to develop
      lymphoproliferative disorders involving polyclonal T cells that produced high
      amounts of T helper-type 2 (Th2) cytokines. This unexpected finding revealed that
      LAT also constitutes a negative regulator of TCR signalling and T cell
      homeostasis. As discussed, the available data underscore that a novel
      immunopathology proper to defective LAT signalosome is likely taking shape.

PMID- 17534069
TI  - Genetic analysis of systemic autoimmunity.
AB  - Even for complex diseases with high rates of monozygotic twin concordance,
      disease-associated alleles remain elusive. One explanation is that multiple
      common genetic variants with weak effects cause these diseases and identification
      of any single allele requires large cohorts. Conversely, if the allelic spectrum
      of complex disease is heterogeneous, strong effects of rare variants might be
      offset by their presence in only a small proportion of the patient population.
      Lupus (SLE) is a systemic autoimmune disease, with significant monozygotic twin
      concordance, protean clinical manifestations, and production of high-affinity
      pathogenic autoantibodies. This complex phenotype and results from genome scans
      point to multiple molecular defects. Contrary to this expectation, our analysis
      of ENU-mutagenized mice indicates that homozygous mutations frequently cause anti
      nuclear antibodies (ANAs), and can account for a full blown lupus phenotype. The
      best characterized example is the sanroque strain, which develops high-affinity
      dsDNA autoantibodies and fails to censor self-reactive germinal centre T cells.
      Mapping the underlying mutation identified not only a novel gene, Roquin, but
      also a novel pathogenic pathway for SLE. Identification of such rare variants
      with strong effects is likely to identify pathogenic pathways that underlie
      pathology in many patients, lead to interacting molecular partners that also
      cause pathology, and identify the most effective therapeutic targets.

PMID- 17534070
TI  - Genetic resistance to smallpox: lessons from mousepox.
AB  - There is increased interest in understanding protective immunity to smallpox for
      two principal reasons. First, it is the only disease that has been successfully
      eradicated using a live virus vaccine and, second, there exists a potential
      threat of intentional or unintentional release of variola virus, the causative
      agent of smallpox. Although mortality rates associated with smallpox were as high
      as 40%, a significant subset of those infected recovered. The basis of
      susceptibility or resistance, and the immune parameters associated with recovery,
      are still unknown. Animal models of poxvirus infections are being employed to
      understand what constitutes an effective host response. Ectromelia virus is
      closely related to variola virus and it causes a disease similar to smallpox in
      mice. This model is well established, resistant and susceptible strains of mice
      are defined and four genetic loci associated with resistance have been
      identified. Susceptibility to infec tion and disease severity is also influenced
      by virus immune evasion strategies. The outcome of infection is clearly dictated
      by several factors including host and viral genes, both of which influence the
      immune response. Here we present data on one virus-encoded immune modifier and
      its effect on the functions of two host genetic loci associ ated with resistance.

PMID- 17534071
TI  - The AcB/BcA recombinant congenic strains of mice: strategies for phenotype
      dissection, mapping and cloning of quantitative trait genes.
AB  - The AcB/BcA gene discovery platform consists of a series of 36 recombinant
      congenic strains (RCS) produced from the second backcross generation of the
      progenitor mouse strains A/J and C57BL/6J. Each individual inbred RCS carries
      12.5% of the donor genome in 87.5% of the background genome. As the two parental
      strains are known to vary in the expression of resistance and susceptibility to a
      considerable number of mouse models of human diseases, the AcB/BcA RCS platform
      represents a valuable and versatile genetic tool to study many different
      phenotypes. RCS can be used to follow the segregation of single gene effects in
      individual strains, or to look at association/dissociation of mechanistic aspects
      of complex phenotypes. In addition, one can select strains with fixed alleles at
      known loci to look for novel gene effects, or use strains with overlapping
      congenic segments to delineate minimal QTL, intervals. The AcB/BcA RCS platform
      was used by our group and others to study a series of complex phenotypes
      including nociception, malaria susceptibility and lipid metabolism. Linkage
      mapping in secondary crosses and gene expression analysis in targeted organs
      allowed the identification of chromosomal regions, genes, and biological pathways
      which might unravel novel targets for preventive and therapeutic interventions.

PMID- 17534072
TI  - Genetic control of host-pathogen interactions in mice.
AB  - The onset, progression and outcome of infections are determined by performance of
      host defence mechanisms and expression of pathogen virulence determinants.
      Genetic analysis in mouse can identify host genes that play critical roles at the
      interface of host-pathogen interactions. Genetic effects detected as variations
      in susceptibility in inbred, recombinant and mutant strains of mice can be mapped
      as simple traits or quantitative trait loci followed by identification by
      positional cloning. We have used mouse models of infection with bacterial
      (Mycobacterium, Legionella) and parasitic pathogens (Plasmodium) to discover
      genes and proteins that are important for macrophage function against such
      infectious agents. These studies have identified Nrampl-mediated exclusion of
      divalent metals from the phagosomal space as a key regulator of intracellular
      replication of Mycobacteria. Also, intracellular sensing of Legionella by
      functional Birc1e/Naip5 protein is essential to prevent replication of this
      bacterium in macrophages. Finally, we have identified two new loci that affect
      blood-stage replication of Plasmodium chabaudi AS in mice, and have cloned the
      corresponding genes.

PMID- 17534073
TI  - Mycobacterium tuberculosis and its ability to resist immunity.
AB  - Resistance to tuberculosis involves a balance between the immune activation
      required to restrict the infection and the immune regulation required to prevent
      collateral damage to surrounding tissues. We explore here the hypothesis that
      genetic diversity of Mycobacterium tuberculosis provides an opportunity to tilt
      this balance in favour of the pathogen through variations in innate immune
      signalling.

PMID- 17534074
TI  - Systems genetics: the next generation in genetics research?

PMID- 17534075
TI  - Regulation of the immune system in metazoan parasite infections.
AB  - Eukaryotic, multicellular parasites such as the helminth worms have a major
      impact on the mammalian immune system in two contexts. First, they have evolved
      sophisticated strategies for long-term immune evasion including recruiting
      natural suppressive mechanisms such as the regulatory T cell (Tregs). Tregs play
      a role not only in repressing immunity to parasites, but also in dampening
      bystander responses such as those to allergens. To achieve these effects, they
      produce a range of immunomodulators some of which are evolutionary homologues of
      immune system cytokines, while others are novel proteins capable of interfering
      with immune cell signalling and differentiation. The second context in which
      metazoa may have influenced their host is at the level of genetic polymorphism in
      immune response genes. Alleles at loci originally associated with predisposition
      to asthma have more recently been found to confer heightened resistance to
      helminth parasites. This may suggest a mechanistic link between more vigorous
      type 2 responses in both allergy and infection. On a broader perspective, one may
      speculate that alleles advantageous in the historical environment of prevalent
      infection, now display a deleterious phenotype in our more 'hygienic' societies.

PMID- 17534076
TI  - The role of CT scan in reversible airflow obstruction.

PMID- 17534077
TI  - Parental discipline of young children.

PMID- 17534078
TI  - Electroconvulsive therapy--an outdated treatment, or one whose time has come?

PMID- 17534079
TI  - Methicillin-resistant Staphylococcus aureus: an established pathogen with
      emerging infections.

PMID- 17534080
TI  - Looking back--then forward--at American medicine.

PMID- 17534081
TI  - The impact of bronchiectasis in clinical presentation of asthma.
AB  - BACKGROUND: Though asthma and bronchiectasis are two different diseases, their
      coexistence has been shown in many patients. The aim of this study was to
      evaluate the clinical features of asthmatics with bronchiectasis compared with
      pure asthmatics. METHODS: We evaluated 1680 asthmatics followed-up in our clinic.
      Fifty-one asthmatics had the diagnosis of bronchiectasis. These patients were
      compared with fifty-one age and gender matched asthmatics without bronchiectasis.
      RESULTS: The prevalence of bronchiectasis among the asthmatics was 3%. Asthma
      diagnosis was made at the age of 33.2 +/- 16.8 years for asthmatics with
      bronchiectasis and 39.5 +/- 16.2 years for pure asthmatics (P = 0.05). Asthmatics
      with bronchiectasis mostly had severe persistent asthma (49.0%), while pure
      asthmatics mostly had mild persistent and intermittent asthma (69.4%). History of
      hospitalization due to severe asthma exacerbation and presence of chronic
      respiratory failure was significantly higher in bronchiectatic group.
      CONCLUSIONS: These data show that bronchiectasis can contribute to severe and
      difficult to control asthma with pulmonary complications like chronic respiratory
      failure.

PMID- 17534082
TI  - A longitudinal study of parental discipline of young children.
AB  - OBJECTIVE: To determine how discipline practices changed over time for young
      children. METHODS: A cohort of parents with young children were interviewed in
      clinic about a broad array of disciplinary practices at two points in time.
      RESULTS: A total of 182 parents were interviewed at Time 1, and 94 were
      interviewed at Time 1 and 2. Mean age of the child was 16.2 months at Time 1 and
      35.8 months at Time 2. Monitoring, verbal communication, and distracting were the
      most common types of discipline when the children were one year old. Corporal
      punishment (P < 0.05), verbal communication (P < 0.001), timeout (< 0.0001),
      removing privileges (< 0.0001), negative demeanor (< 0.0001), and sternness (<
      0.0001) increased significantly from Time 1 to Time 2. Distracting (< 0.001)
      decreased significantly and positive demeanor also decreased. CONCLUSIONS: Most
      discipline practices increased in frequency over the 20 months of this study. The
      increase in parental negative demeanor seems particularly important and worthy of
      further study.

PMID- 17534083
TI  - Prevalence of Chlamydia trachomatis among active duty male soldiers reporting to
      a troop medical clinic for routine health care.
AB  - OBJECTIVE: To determine the prevalence of chlamydia among young, male soldiers
      receiving routine healthcare and to measure risk factors associated with sexually
      transmitted infections (STI). MATERIALS AND METHODS: Male soldiers between the
      ages of 18 to 25 years seeking routine healthcare were screened for chlamydia.
      Educational information regarding Chlamydia trachomatis was provided before
      testing. The transcription-mediated amplification (TMA) urine-based test was used
      as a sensitive and specific screening tool to detect disease. Assessment of risk
      factors was determined by questionnaire. Subjects who tested positive for
      chlamydia were treated with azithromycin 1 g in a single dose. RESULTS: A total
      of 138 male soldiers were screened for chlamydia. The majority of soldiers
      screened reported to sick call for evaluation of an injury, 31.9%. The estimated
      prevalence of chlamydia was 8.0% (95% CI: 0.035-0.125). Soldiers who tested
      positive for chlamydia were more commonly asymptomatic, 72.7%. Of those who
      screened positive for chlamydia, 63.6% did not use a condom during their last
      encounter. No subjects who tested positive for disease had been treated for an
      STI in the past. CONCLUSIONS: The prevalence of chlamydia in this population of
      young, male soldiers is high. These results should spur providers to incorporate
      STI risk assessment and screening into a variety of clinical encounters.

PMID- 17534084
TI  - The influence of payer mix and visit volume on NRMP match rates for community
      based family medicine residency programs.
AB  - BACKGROUND: With declining U.S. medical student interest in family medicine, it
      is important to study factors that may predict for individual residency program
      fill rates. Predictors of family medicine residency program match rates are few,
      with location by region of the country being the best predictor. Using a limited
      database, this study evaluated whether community-based residency program match
      rates are associated with patient visit volume and payer status. METHODS: An
      existing database of characteristics of 42 community-based family medicine
      residency programs was analyzed for associations of match rate with patient visit
      volume and with insurance payer status. RESULTS: Nonsignificant correlations were
      calculated for match rate with the following factors: patient visit volume per
      provider, percentage of patient visits with no insurance or with Medicaid
      payment, percentage of visits with Medicare payment, and percentage of visits
      with private third party payers. A marginal negative association of match rate
      with percentage of patient visits with Medicare payment was not significant when
      adjusted for region of the country. CONCLUSIONS: In this study, neither patient
      visit volume nor payer status were predictive of match rate for community-based
      family medicine residency programs. Limitations to this study are acknowledged.

PMID- 17534085
TI  - Perioperative cardiac evaluation: novel interventions and clinical challenges.
AB  - Cardiac complications are one of the most important sources of morbidity and
      mortality after noncardiac surgery. In this review, we discuss the
      pathophysiology of postoperative cardiac complications and published risk indices
      and guidelines that allow an estimation of preoperative risk. Recent evidence has
      challenged the primary role of perioperative beta blockers as a risk reduction
      strategy. The highest level of evidence for their use is for patients with
      coronary artery disease or multiple risk factors undergoing vascular surgery.
      Beta blockers may provide no benefit or may be potentially harmful for low- and
      intermediate-risk patients and surgeries. For patients with contraindications to
      beta blockers, diltiazem and clonidine are alternative agents that reduce cardiac
      risk. Statins are emerging as another potential strategy to reduce cardiac risk,
      although the evidence is based primarily on retrospective analyses. Coronary
      artery revascularization does not reduce cardiac complications after noncardiac
      surgery among patients with stable coronary artery disease.

PMID- 17534086
TI  - Electroconvulsive therapy: a review of history, patient selection, technique, and
      medication management.
AB  - Electroconvulsive therapy (ECT) is a safe and effective treatment for severe and
      persistent depression, bipolar disorder and schizophrenia. Though ECT is now over
      60 years old, it remains an underutilized treatment today. History, patient
      selection, safety, and characteristics of the treatment stimulus, technique, and
      medications used in ECT are reviewed. Dosing strategies, as pertaining to seizure
      threshold, will be considered. Mechanisms of action, especially with regard to
      serotonin, norepinephrine, and dopamine receptor expression will be discussed.

PMID- 17534087
TI  - Recognizing the link between CKD and CVD in the primary care setting: accurate
      and early diagnosis for timely and appropriate intervention.
AB  - Chronic kidney disease (CKD), which is becoming increasingly prevalent in the US
      and worldwide, eventually progresses to end-stage renal disease (ESRD), requiring
      renal replacement therapy. Diabetes and hypertension, the two leading causes of
      CKD, are themselves reaching near epidemic proportions. Hypertension can cause
      both the development and progression of CKD, and CKD is a significant risk factor
      for the development of cardiovascular disease. Indeed, CKD patients are more
      likely to die of cardiovascular complications than progress to ESRD. However,
      data indicate that early recognition and management of CKD can have a significant
      positive impact on disease outcome. This creates an important interventional
      opportunity for the primary care physician. This report describes the major risk
      factors and comorbidities associated with the development and progression of CKD
      and offers suggestions for timely diagnosis and management of CKD in the primary
      care setting.

PMID- 17534088
TI  - Bacteroides fragilis vertebral osteomyelitis: case report and a review of the
      literature.
AB  - BACKGROUND: To review the presentation of Bacteroides fragilis (B fragilis)
      spondylodiscitis. METHODS: Two investigators independently searched the published
      English, Spanish and French languages literature through September 2005 using
      MEDLINE (1966-2005). We included all reported cases of vertebral osteomyelitis or
      spondylodiscitis caused by B fragilis, not related to sacral decubitus ulcers, in
      adults (age 16 yr and above). A third author independently reviewed all articles
      and extracted data for accuracy. The final pool of eligible publications included
      11 articles, publication dates ranging from 1978 to 2005. Eight were written in
      English, two in Spanish, and one in French. RESULTS: The age of the patients in
      this series ranged from 17 to 74 years, with a mean age of 55 years. Male to
      female ratio was 6:1. Lumbar involvement was reported in nine cases, thoracic
      involvement in two patients and sacral involvement in one patient. B fragilis was
      recovered by blood culture in four patients and by tissue culture in eight
      patients. Metronidazole was the most common antibiotic used for treatment (eight
      patients), either as monotherapy or in combination with other antibiotics.
      CONCLUSIONS: B fragilis is a rare causative agent of spondylodiscitis, but it
      should be considered in patients with spondylodiscitis who have contiguous
      intraabdominal or pelvic infections or who had recent gastrointestinal procedures
      that may have led to B fragilis bacteremia.

PMID- 17534089
TI  - Overlapping features of thrombotic thrombocytopenic purpura and systemic lupus
      erythematosus.

PMID- 17534090
TI  - Dual perinephric and prostatic abscesses from methacillin-resistant
      Staphylococcus aureus.
AB  - Perinephric and prostatic abscesses may present with protean symptoms and often
      arise from ascending urinary tract infections. Both abscesses are often caused by
      uropathogens, and only on rare occasions is the etiology due to methacillin
      resistant Staphylococcus aureus (MRSA). Perinephric and prostatic abscesses have
      never been reported to occur together. We present a 56-year-old male with poorly
      controlled diabetes that had recently begun performing daily self-digital rectal
      examinations, who presented with a three day history of urinary symptoms. The
      patient had bilateral costovertebral angle tenderness and a boggy, tender,
      enlarged prostate. Blood and urine cultures showed MRSA. CT scan of the abdomen
      and pelvis demonstrated right perinephric abscess and prostatic abscess. This
      case report illustrates the potential for simultaneous perinephric and prostatic
      abscesses by MRSA.

PMID- 17534091
TI  - Coccidioidomycosis pneumonia in a nonendemic area associated with infliximab.
AB  - Tumor necrosis factor (TNF) inhibitors, such as infliximab, are highly effective
      in the management of rheumatoid arthritis; however, these agents are associated
      with an increased risk of infectious complications. Individuals developing
      coccidiomycosis pneumonia frequently acquire this while residing in endemic
      regions. We present a patient with rheumatoid arthritis treated with infliximab
      who developed acute respiratory distress syndrome (ARDS) from coccidiomycosis
      pneumonia while residing in a non-endemic region near the Texas-Louisiana border
      and was successfully treated with antifungal therapy. The source for
      coccidiomycosis was suspected to be from inhalation of pulverized rock dust
      imported from Arizona. Patients treated with TNF inhibitors may acquire
      coccidiomycosis infection through fomite dust exposure.

PMID- 17534092
TI  - Urinothorax: a rapidly accumulating transudative pleural effusion in a 64-year
      old man.
AB  - We report the case of a 64-year-old man who developed a rapid, right-sided
      pleural effusion. On initial presentation to the emergency room, the patient had
      fever and flank pain consistent with a ureteral obstruction (due to a bladder
      tumor) and associated hydronephrosis that had required previous placement of a
      pericutaneous nephrostomy tube. After a 10-day stay in the hospital, the
      patient's urine output ceased. Symptomatic dyspnea with radiographic evidence of
      a new pleural effusion soon followed. Urinothorax was the etiology of the
      effusion.

PMID- 17534093
TI  - Buerger disease in an elderly man.
AB  - Buerger disease is characterized by progressive distal extremity ischemia in
      persons with recent tobacco consumption. Typically, affected persons are young
      men. There have been case reports of Buerger disease in older men. Almost all of
      the reported cases were characterized with progressive, severe disease requiring
      amputation. We report a case of an older man with features of Buerger disease
      without significant proximal progression despite active smoking. Arteriographic
      and pathologic studies confirmed the diagnosis.

PMID- 17534094
TI  - Coincidental consort clear cell cutaneous carcinoma: facial squamous cell
      carcinoma in situ containing human papillomavirus and cancer cells with clear
      cytoplasm in an octogenarian couple.
AB  - Clear cell squamous cell carcinoma in situ, also referred to as pagetoid or clear
      cell Bowen disease, is a rare pathologic variant of this neoplasm. It is
      characterized by neoplastic cells with clear or pale cytoplasm. An octogenarian
      husband and wife concurrently developed new facial skin lesions which
      demonstrated squamous cell carcinoma in situ consisting of cancer cells with
      clear cytoplasm. Cutaneous human papillomavirus (HPV) typing detected HPV Type 5
      and HPV Type 21 in the tumors of the husband and wife, respectively. HPV is a
      potential etiologic factor in the oncogenesis of nonmelanoma skin cancer, and HPV
      DNA has been demonstrated in extragenital squamous cell carcinoma in situ. The
      detection of DNA from different HPV types in the tumors of our patients suggests
      that the concurrent occurrence of their skin cancers may have been coincidental.
      However, the presence of HPV DNA in their tumors introduces the possibility of a
      viral-associated oncogenesis for clear cell squamous cell carcinoma in situ.

PMID- 17534095
TI  - Lactobacillus septic arthritis.
AB  - Lactobacillus is a Gram positive bacteria found in the mouth, gastrointestinal
      and female genital tract. Serious infections due to Lactobacillus are becoming
      increasingly common. We present a 49-year-old diabetic patient with Lactobacillus
      septic arthritis. To our knowledge, this is the first reported case. Usually,
      Lactobacillus is implicated with bacteremia, endocarditis and more rarely
      pneumonia, meningitis and endovascular infection, and half of the cases are
      reported in immunocompromised patients. As in our patient, diabetes mellitus is a
      comorbid condition which has been clearly noted. Our finding suggests that
      further studies are necessary to establish the significance of Lactobacillus as
      an etiologic agent of septic arthritis.

PMID- 17534096
TI  - Spontaneous cholesterol crystal embolization to bone marrow.
AB  - Cholesterol crystal embolization is a well-established complication of arterial
      trauma and anticoagulation which may involve multiple organs including the skin
      and muscle, producing clinical features such as livedo reticularis, cyanosis and
      gangrene of the toes and intense myalgias. Cholesterol crystal embolization to
      bone marrow has been described in postmortem studies, but has been previously
      reported premortem in only two patients, both of whom had characteristic risk
      factors and clinical features. We report herein a case of spontaneous cholesterol
      crystal embolization to bone marrow in a patient with atypical clinical
      manifestations.

PMID- 17534097
TI  - Squamous cell carcinoma in situ in a female urethral diverticulum.
AB  - There have been less than 100 reported cases of carcinoma in a female urethral
      diverticulum, with only 10 of these cases being squamous cell carcinoma (SCC).
      The course of this disease is frequently aggressive, despite multimodality
      treatment, and most patients die within 2 to 3 years. To our knowledge, carcinoma
      in situ of the female urethral diverticulum has not been reported to date, and
      thus, optimal treatment is not well defined. A 41-year-old woman was found to
      have SCC in situ without evidence of invasive carcinoma after diverticulectomy.
      She elected close observation and remains disease-free at 2 years. A brief
      overview is given of the presentation, management, and outcomes of urethral
      diverticular carcinoma.

PMID- 17534098
TI  - Unilateral shivering: a result of lateral medullary infarction.
AB  - Shivering is mediated via the predominantly uncrossed reticulospinal tract. We
      report a case of a patient with left lateral medullary tract infarct involving
      the reticulospinal tract who displayed ipsilateral absence of shivering during a
      febrile episode. The physiology and anatomy of shivering and the reticulospinal
      tract is reviewed.

PMID- 17534099
TI  - Ilioinguinal-inguinal nerve block for hernia repair.

PMID- 17534100
TI  - Aspartame-induced thrombocytopenia.

PMID- 17534101
TI  - Rhabdomyolysis associated with pulmonary tuberculosis.

PMID- 17534102
TI  - Retroperitoneal fibrosis as a long-term complication of radiation treatment for
      prostate cancer.

PMID- 17534103
TI  - Electrical storm and implanted defibrillators.

PMID- 17534104
TI  - Acute pancreatitis induced by adult precursor B-cell acute lymphoblastic leukemia
      associated with complex cytogenetics.

PMID- 17534105
TI  - Classical nodular sclerosis Hodgkin lymphoma presenting with central nervous
      system disease.

PMID- 17534106
TI  - Patient's page. Electroconvulsive therapy.

PMID- 17534107
TI  - Ageing and autobiographical memory for emotional and neutral events.
AB  - We investigated age-related effects in recall of emotional and neutral
      autobiographical memories. Protocols were scored according to episodic and non
      episodic detail categories using the Autobiographical Interview. Young adults
      recalled a greater number of episodic details compared to older adults, whereas
      older adults recalled more semantic details, replicating previous findings. Both
      young and older adults' emotional memories contained more overall detail than
      neutral ones, with the enhancement from emotion-specific to episodic details, but
      this did not alter the effect of age group on the pattern of episodic and
      semantic details. However, the age effect on episodic details was attenuated for
      neutral autobiographical memories. The findings suggest that age differences for
      emotional autobiographical recollection might reflect a more general pattern of
      age-related changes in memory, with impaired recall of episodic components and
      relative sparing of semantic aspects of autobiographical memory in older adults
      when compared to young adults.

PMID- 17534108
TI  - PTSD psychiatric patients exhibit a deficit in remembering.
AB  - This study investigated the effects of PTSD on levels of awareness in a
      recognition memory task. A group of PTSD psychiatric patients and a control group
      without any traumatic experience were compared in remembering (R) versus knowing
      (K) recognition using non-trauma-related words. Results showed that overall
      recognition did not differ between the two groups, but in the PTSD group a
      significantly different pattern of Remember and Know responses was produced,
      indicating a shift from remembering to knowing. However, this shift from
      remembering to knowing in individuals with PTSD is associated with modifications
      in the trait anxiety level. These results are interpreted within theoretical
      frameworks in which R responses could be associated with distinctiveness
      (Rajaram, 1996) and conceptual processing (Ehlers & Clark, 2000). These
      collective findings would suggest the possibility that a poor general ability in
      the formation of source memory may eventually be a common characteristic across
      different types of PTSD.

PMID- 17534109
TI  - Effect of negative emotional pictures on associative memory for peripheral
      information.
AB  - We investigated the influence of negative emotional pictures on associative
      memory. A visual object was embedded in the periphery of negative emotional or
      neutral pictures. Memory was assessed for central item (pictorial) information,
      peripheral (object) information, and the association between item and peripheral
      information. On tests of item information, negative emotional pictures were
      remembered better than neutral pictures. However, associative memory between item
      and peripheral information was less accurate when the pictures were negative
      compared to neutral. This occurred despite equivalent recall (Experiments 1 and
      2) and recognition (Experiment 2) for the peripheral objects themselves. Further
      experiments confirmed that performance on the associative test was not influenced
      by testing order (Experiment 3). These findings suggest that negative emotional
      arousal can particularly disrupt the associative binding of peripheral
      information to a central emotional event.

PMID- 17534110
TI  - Are tip-of-the-tongue states universal? Evidence from the speakers of an
      unwritten language.
AB  - Schwartz (1999, 2002) has claimed that tip-of-the-tongue states (TOTs) are
      universal. The studies reported in this paper examine this claim for illiterates,
      unschooled literates, and schooled readers, all speakers of an unwritten
      Guatemalan language. The first study showed that, although there was little
      evidence of a dedicated verbal expression for this state of consciousness in the
      Mayan language of Q'eqchi', a majority of participants in all three groups
      recognised a description of the phenomenology associated with tip-of-the-tongue
      states. In two further studies it was shown that TOTs could be induced in all
      groups of participants, and that they were reliably resolved by the presentation
      of the words' initials. Thus, even in the absence of an expression for "tip-of
      the-tongue state", the basic phenomenology and cueing properties of TOTs were
      similar to those reported in previous studies. However, only university-level
      participants reported partial knowledge of word targets they had failed to
      recall. The results are discussed from psycholinguistic and metacognitive
      perspectives, drawing a possible link between TOTs and epistemic curiosity.

PMID- 17534111
TI  - Factors shaping vividness of memory episodes: visitors' long-term memories of the
      1970 Japan World Exposition.
AB  - This study investigated how visitors' psychological and behavioural factors,
      identified in the literature, shaped their vivid long-term memories of their
      experiences of the Japan World Exposition, Osaka, 1970 (Expo '70) as a context.
      In this study, 112 memory episodes were identified from the long-term memories of
      48 participants; they were rated in terms of their memory vividness and on a set
      of factors including affect, agenda fulfilment, intentionality, and rehearsal.
      The influence of these factors on the vividness of episodic and/or autobiographic
      memories of experiences that occurred 34 years ago was examined in two stages.
      First, the relationship between memory vividness and individual factors was
      investigated separately. Second, the relationship between memory vividness and
      all factors was examined through a multiple regression analysis, and the relative
      importance of these factors on memory vividness identified. Stage one analysis
      showed that all factors except intentionality were related to memory vividness in
      individual analyses, and curvilinear relationships between memory vividness and
      the factors found. Stage two analysis, in which all factors were included in a
      multiple regression analysis, found that rehearsal was positively related to
      memory vividness and all other factors not significant in the presence of
      rehearsal.

PMID- 17534112
TI  - Memory for emotional and neutral information: gender and individual differences
      in emotional sensitivity.
AB  - In studies of autobiographical memory, women typically remember more emotional
      information than do men. The present study evaluated whether women recall more
      emotional information than men when the content of an event is controlled.
      Participants read a script containing emotional and neutral information, under
      instructions to prepare advice for the characters addressing either interpersonal
      issues (emotional focus), concrete plans (neutral focus), or with no particular
      topic suggested (undirected focus). After writing out advice, on a surprise
      memory test women recalled more emotional information than men in all focus
      conditions with no deficit in neutral recall. Women recalled more neutral
      information than men in the neutral focus condition. A measure of emotional
      sensitivity mediated the gender difference in emotional recall suggesting that
      memory for emotional information is not solely a function of gender.

PMID- 17534113
TI  - Memories of real-life decisions.
AB  - Three studies investigated decision makers' memory representations of choice
      alternatives in most important real-life decisions. In Study 1, each participant
      recalled the most important decision that she or he had ever made and rated to
      what degree a number of characteristics could describe the decisions. In Study 2,
      the participants were asked to think about an important decision that they had
      made during the last 7-10 days. In Study 3, the memory representations of
      decisions of a group of action-oriented participants were compared with those of
      a group of state-oriented participants (Kuhl, 1983). Characteristics related to
      standard decision theory, like consequences, values, and likelihood, had high
      ratings of applicability as well as affect/feeling. When testing the
      applicability of a circumplex model, the fuzzy-trace theory of memory, and
      differences between state- and action-oriented decision makers, we found (1) that
      there was no support for the circumplex model of emotions. Instead, an important
      decision problem was characterised by both positive and negative affect/emotion
      and thus, a bipolar mapping was found inadequate; (2) that a comparison of
      abstract and concrete aspects showed that the abstract characteristics scored
      higher, thereby supporting the fuzzy-trace theory; and (3) that the prediction
      that action-oriented participants would score higher than state-oriented
      participants on the characteristic of activity was not supported. However, state
      oriented decision makers rated passivity higher than action-oriented decision
      makers for the important decision of leaving a partner. State-oriented decision
      makers used perceptual/cognitive scenario representations to a greater extent
      than action-oriented participants. Finally, it was stressed that in the
      development of decision theories it is essential to find theoretical
      representations as close as possible to how decision makers themselves represent
      the decisions. The method used in this contribution is focused on the role of
      memory in decision making and gives further insights into how important real-life
      decisions are represented by different decision makers.

PMID- 17534114
TI  - Balance of vascular endothelial growth factor and pigment epithelial growth
      factor prior to development of proliferative vitreoretinopathy.
AB  - BACKGROUND: Pigment epithelium-derived factor (PEDF) and vascular endothelial
      growth factor (VEGF) are imbalanced in eyes with proliferative diabetic
      retinopathy or proliferative vitreoretinopathy (PVR). It is not known whether
      such an imbalance is already present in early PVR stages. We therefore analyzed
      VEGF and PEDF concentrations in subretinal fluids prior to PVR development.
      METHODS: A large number (n = 137) of subretinal fluid samples were obtained at
      the time of scleral buckling surgery for rhegmatogenous retinal detachment (RRD).
      Thirty patients developed PVR within 6 months after surgery. One hundred and
      seven patients undergoing the same surgery but without complications served as
      controls. Furthermore, vitreous from 16 patients with macular hole or pucker
      (MHP) served as reference for baseline intraocular concentrations. PEDF and VEGF
      concentrations were measured by commercial ELISAs. RESULTS: PEDF levels were
      substantially higher (9.6 microg/ml) compared to MHP vitreous (0.3 microg/ml, p <
      0.001). VEGF levels were also higher (RRD: 0.07 ng/ml; MHP: 0.01 ng/ml, p <
      0.05). Subretinal concentrations were not significantly different between PVR and
      control RRD patients. CONCLUSIONS: Although both VEGF and PEDF are increased at
      first surgery for RRD, they do not predict PVR development later on. The high
      PEDF concentrations and its known antiangiogenic activity suggest a protective
      role against neovascularization.

PMID- 17534115
TI  - Distinct functions between toll-like receptors 3 and 9 in retinal pigment
      epithelial cells.
AB  - Retinal pigment epithelial cells (RPE cells) are key players in the first-line
      defense against invading organisms such as viruses and bacteria. The interaction
      between RPE cells and viral or bacterial components is very important for
      clearance of these organisms. Toll-like receptors are a family of recognition
      receptors involved in innate immunity. Each TLR acts as a primary sensor of
      conserved microbial components and drives the induction of specific biological
      responses. TLR 3 is involved in the recognition of viral components, such as
      double-stranded RNA (dsRNA) and poly(I:C), while TLR 9 recognizes viral or
      bacterial DNA without methylation at CpG motifs. In the present study, we
      investigated the expression and function of TLR 3 and 9 in RPE cells. PCR
      analysis revealed expression of genes for TLR 3 and 9 in RPE cells. Expression of
      TLR 3 and 9 protein was detected in RPE cells by flow cytometry. TLR 3 and 9
      showed strong intracellular expression. To detect angiogenetic factors produced
      by RPE cells, culture supernatant was examined with the Human Angiogenesis
      Antibody Array, which can simultaneously detect 20 different angiogenetic factors
      including cytokines, chemokines, soluble cytokine receptors, and growth factors.
      RPE cells showed high production of interleukin-8 (IL-8) and monocyte chemotactic
      protein-I (MCP-I). Furthermore, stimulation of RPE cells with the dsRNA analogue
      poly(I:C) enhanced the secretion of IL-8 and MCP-I, as well as enhancing the
      expression of junctional adhesion molecule-I (Jam-I) and intracellular adhesion
      molecule-I (ICAM-I), and promoted the adhesion of monocyte to these cells. In
      contrast, stimulation with the CpG-DNA motif only enhanced the secretion of IL-8.
      However, CpG-DNA motif enhanced phagocytosis in RPE cells. These results may
      indicate that TLR 3 and 9 play a distinct role in the inflammatory response that
      clears viruses from the retina.

PMID- 17534116
TI  - Modulation of Ku70/80, clusterin/ApoJ isoforms and Bax expression in indocyanine
      green-mediated photo-oxidative cell damage.
AB  - PURPOSE: In order to characterize the biological effects and molecular mechanism
      underlying indocyanine-green (ICG)-mediated photo-oxidative cell damage, human
      cultured retinal pigmented epithelium (RPE) cells preloaded with ICG were exposed
      to 810-nm laser irradiation. Cell viability and death induction were examined, as
      well as the modulation of proteins involved in cell death and DNA repair.
      METHODS: ARPE-19 cells preloaded with 100 microM ICG were irradiated using
      continuous and micropulsed 810-nm laser for the dye photoactivation, and cell
      viability and apoptosis were evaluated. The expression and subcellular
      localization of Bax, Ku70, Ku80 and clusterin/ApoJ were analyzed by
      immunocytochemistry and Western blot. RESULTS: ICG photoactivation induced
      apoptosis in RPE cells. The micropulsed laser irradiation induced a higher
      percentage of cell killing as compared to continuous wave. Cell killing was
      inhibited by sodium azide, suggesting the involvement of reactive oxygen species
      in the laser-induced cell damage. Bax was strongly induced after 4 and up to 24 h
      of treatment. The nuclear proapoptotic isoform of clusterin/ApoJ was selectively
      upregulated after 24 h of treatment. The DNA repair machinery was upregulated
      after 4 and up to 24 h. CONCLUSION: These data elucidate some molecular
      mechanisms involved in cell death induced by ICG photosensitization. The increase
      and relocalization of Bax into the mitochondria and the upregulation and
      translocation of the proapoptotic isoform of clusterin/ApoJ in the nucleus
      demonstrated the involvement of these proteins in the photo-oxidative cell death
      pathway. These data point out new molecular targets and suggest potential
      applications in the therapy of the retinal diseases that could benefit by
      selective RPE treatment.

PMID- 17534117
TI  - Distribution and expression of RhoA in rat retina after optic nerve injury.
AB  - BACKGROUND: RhoA is a small guanosine triphosphatase which participates in
      signaling pathways of axonal repellents or inhibitors. However, the distribution
      and expression of RhoA in the rat retina after optic nerve injury has not been
      elucidated yet. OBJECTIVES: To study the distribution and expression of RhoA in
      the rat retina after optic nerve injury. METHODS: Immunohistochemistry was used
      to determine the distribution of RhoA in rat retina after optic nerve injury. The
      expression of RhoA was analyzed by Western blot. RESULTS: In normal retina and
      the retina 1 day after optic nerve injury, RhoA was distributed in the retinal
      ganglion cell (RGC) layer. Three days after optic nerve injury, it existed in
      RGCs and the inner plexiform layer. However, 7 days after surgery its
      immunoreactivity was abundant not only in the RGC and inner plexiform layers but
      also in the inner nuclear and outer plexiform layers. Western blot analysis
      showed that the expression of RhoA increased significantly in the retina after
      optic nerve injury in comparison with normal retina. CONCLUSION: These results
      indicate that the distribution and expression of RhoA were extended and enhanced
      after optic nerve injury, and that RhoA plays an important role in optic nerve
      regeneration.

PMID- 17534118
TI  - Eccentric lamellar keratolimbal grafts harvested with a manually guided
      microkeratome. Technical report.
AB  - BACKGROUND: To perform lamellar keratolimbal allograft transplantation in a one
      step procedure with a single graft, we investigated the feasibility of harvesting
      eccentric lamellar keratolimbal grafts from conventionally processed
      corneoscleral buttons using a manually guided microkeratome in conjunction with
      an artificial anterior chamber system. METHODS: We used the Moria LSK-One
      microkeratome and the automated lamellar therapeutic keratoplasty (ALTK) system
      (Antony, France). Ten human donor eyes were used to obtain single-piece lamellar
      keratolimbal grafts. Specimens were processed for light and electron microscopy.
      RESULTS: Eccentric keratolimbal grafts could be obtained from all human donor
      buttons. Grafts include a crescent-shaped limbal and a large corneal portion. No
      visible damage to the limbal region was discernible. CONCLUSION: Our data show
      that the LSK-One microkeratome in conjunction with the ALTK system allows
      harvesting eccentric keratolimbal grafts from donor corneoscleral buttons.

PMID- 17534119
TI  - Rituximab as a treatment option for refractory endogenous anterior uveitis.
AB  - BACKGROUND: To report on anti-CD20 antibody therapy in a patient with uveitis
      refractive to immunosuppression therapy. METHODS: Case report with
      ophthalmoscopic, optical coherence tomography and fluorescein-angiographic
      findings. RESULTS: A 49-year-old woman was suffering from bilateral,
      noninfectious chronic anterior uveitis refractive to corticosteroids and
      immunosuppressive drugs. Bilateral visual acuity was 20/100 due to cataract and
      cystoid macular edema (CME). After treatment with rituximab, vision and CME
      improved, and uveitis was stable until the final visit (follow-up at 12 months).
      CONCLUSION: The case report suggests that rituximab may be helpful for selected
      patients with chronic anterior uveitis refractive to corticosteroids and
      immunosuppressive medication.

PMID- 17534120
TI  - Rosiglitazone ameliorates diabetic nephropathy by inhibiting reactive oxygen
      species and its downstream-signaling pathways.
AB  - AIM: To study whether rosiglitazone prevents the development of diabetic
      nephropathy through reduction of reactive oxygen species and its downstream
      signal transduction pathways. METHODS: The rats were intraperitoneally injected
      with streptozotocin to induce diabetes, meanwhile the rats in the therapeutic
      groups were given rosiglitazone (5 or 20 mg/kg/day) for 4 weeks by intragastric
      administration. Blood glucose, serum lipid and creatinine, urinary albumin
      excretion were measured. Malondialdehyde content, the activities of nuclear
      factor-kappaB (NF-kappaB), antioxidant enzymes including Cu-Zn SOD and GSH-Px in
      kidney were also measured. In addition, the mRNA and protein expression of MCP-1
      were semiquantitatively determined with PT-PCR and immunohistochemical staining
      respectively. RESULTS: No significant difference of blood glucose and lipid were
      found between diabetic rats and rosiglitazone treatment groups. The renal
      histopathology was improved significantly. The expressions of MCP-1 mRNA and
      protein, malondialdehyde level and the activity of NF-kappaB were decreased
      markedly in rats treated with high-dose rosiglitazone, but the activities of
      renal Cu-Zn SOD and GSH-Px increased significantly. CONCLUSIONS: Rosiglitazone
      treatment prevented glomerular injury in diabetic rats, which was closely related
      with its roles of reducing reactive oxygen species, NF-kappaB activation and MCP
      1 expression in the early phase of diabetic nephropathy.

PMID- 17534121
TI  - Beneficial effect of atorvastatin on left ventricular remodeling in spontaneously
      hypertensive rats.
AB  - This study was designed to investigate whether atorvastatin has a beneficial
      effect on left ventricular (LV) remodeling in spontaneously hypertensive rats
      (SHR), and then explore the underlying mechanisms involved. 12 SHRs were
      randomized to receive either distilled water (SHR group, n = 6) or atorvastatin
      (ATV group, n = 6) for 10 weeks. Age-matched Wistar-Kyoto rats (WKY) gavaged by
      distilled water were used as normal controls (WKY group, n = 6). By using these
      rats, we observed the effects of atorvastatin on LV hypertrophy and fibrosis, and
      investigated atorvastatin-induced cell apoptosis and p27 protein expression. In
      addition, the serum lipid concentration and blood pressure level were also
      measured in this study. 10 weeks later, a significant decrease in the
      cardiosomatic ratio, LV weight to body weight ratio and cardiomyocyte transverse
      diameter, as well as myocardial hydroxyproline and collagen content was observed
      in the atorvastatin-treated SHR. In addition, atorvastatin increased the positive
      rate of cell apoptosis and p27 protein expression. A decreased serum lipid
      concentration and a reduced systolic blood pressure level were also found in the
      atorvastatin-treated SHR. These findings demonstrated a beneficial effect of
      atorvastatin on adverse LV remodeling in SHR, and the induction of cell apoptosis
      and upregulation of p27 protein may serve as the underlying mechanisms of this
      action.

PMID- 17534122
TI  - Involvement of NMDA receptors in thiopental-induced loss of righting reflex,
      antinociception and anticonvulsion effects in mice.
AB  - Potentiation of GABA(A) receptor-mediated inhibitory neurotransmission
      contributes to the anesthetic action of thiopental. However, the inhibiting
      action of general anesthetic on excitatory neurotransmission also purportedly
      underlies its effects. The aim of the study was to elucidate the role of
      glutamate receptors (NMDA and AMPA receptors) in thiopental-induced anesthesia.
      Intracerebroventricular (i.c.v.) NMDA (50 ng) significantly increased the
      induction time of loss of righting reflex and decreased sleep time induced by
      intraperitoneal injection (i.p.) of thiopental (50 mg/kg). Furthermore, NMDA at
      50 ng i.c.v. increased the 50% effective dose values for thiopental to produce
      loss of righting reflex and immobility in response to noxious tail clamp by 25%
      and 21% (p < 0.05), respectively. However, intrathecal (IT) administration of
      NMDA or both of i.c.v. or IT administration of AMPA did not show such
      antagonizing effects on thiopental action at subconvulsive dose. Finally,
      thiopental (25 mg/kg i.p.) inhibited convulsions induced by NMDA (0.4 microg
      i.c.v.) or bicuculline (0.6 microg i.c.v.). However, i.p. muscimol (1 mg/kg)
      blocked the convulsions induced by bicuculline, but not those induced by NMDA at
      3 mg/kg. Similarly, i.p. MK-801 (0.1 mg/kg) antagonized NMDA-induced convulsions,
      but not bicuculline-induced convulsions at 0.3 mg/kg. Therefore, we suggest that
      the effects of the selective GABA(A) and NMDA receptors on convulsive behavior
      are special to their sites of action, and that the inhibitory action of
      thiopental on NMDA receptors is possibly not mediated by secondary effects of its
      GABA(A) receptors agonism. These results above indicate the involvement of NMDA
      receptors in thiopental-induced anesthesia in mice.

PMID- 17534123
TI  - Resveratrol-induced apoptosis is associated with activation of p53 and inhibition
      of protein translation in T47D human breast cancer cells.
AB  - BACKGROUND AND PURPOSE: Trans-resveratrol (RSVL; 3,4',5-trihydroxystilbene), a
      natural compound found in grapes, berries, peanuts and red wine exerts certain
      anticancer roles in different human cancer types. However, the exact molecular
      mechanism(s) behind such a role remains to be elucidated, thus the aim of this
      study. EXPERIMENTAL APPROACH: T47D human breast cancer cells were treated with
      RSVL and cell proliferation was measured by cell counting. Apoptosis was analyzed
      by Giemsa staining, poly(ADP-ribose) polymerase (PARP) fragmentation analysis and
      annexin V assay. Regulation of p53 tumor suppressor protein, p70S6K, and pS6
      ribosomal protein was measured by detecting their phosphorylated active forms
      using ECL-immunoblot analysis. RESULTS: The present results show that RSVL
      induced growth inhibition in T47D cells is caused by apoptosis as demonstrated by
      morphological changes and PARP fragmentation. RSVL-induced apoptosis is
      associated with the activation of the p53 in a dose- and a time-dependent manner.
      Phosphatidylinositol 3-kinase (PI3K) inhibitors, wortmannin and LY294002
      abolished the effect of RSVL on p53 activation. Interestingly, RSVL inhibits the
      expression of p70S6K and the phosphorylation of pS6RP. CONCLUSIONS AND
      IMPLICATIONS: These findings demonstrate that RSVL affects multiple intracellular
      signaling transduction pathways such as p53 activation/protein translation
      inhibition/apoptosis, and strongly support a contemplated use of this natural
      compound as a preventive and/or an adjuvant therapeutic drug for breast cancer.
      The data indicate that these proteins may be used as predictive biomarkers to
      evaluate the treatment efficacy of RSVL in clinical trials.

PMID- 17534124
TI  - Chronic administration of carvedilol improves cardiac function in 6-month-old
      Syrian cardiomyopathic hamsters.
AB  - Heart failure (HF) is a multifactorial and progressive disease that has been
      linked to activation of the renin-angiotensin and sympathetic systems. In recent
      years, beta-blockers have been shown to improve the status of HF patients,
      although the precise mechanisms remain unclear. The present study evaluates the
      effect of beta-blockade with carvedilol (1 mg/kg/day) on cardiovascular function
      in 2- and 6-month-old cardiomyopathic hamsters (SCH) after 1-month and 5-month
      treatment periods with the drug, respectively. Age-matched golden hamsters were
      used as controls (CT). Systolic blood pressure (SBP) and echocardiographic
      studies were evaluated. The latter studies included left ventricular end-systolic
      (LVESV) and end-diastolic (LVEDV) volumes, ejection fraction (EF), cardiac output
      index (COI), heart rate (HR), and left ventricular posterior wall thickness
      (LVPWT). In 2-month-old SCH, carvedilol administration during a 1-month period
      reduced SBP from 107.59 +/- 3.49 to 77.26 +/- 3.49 mm Hg (n = 5, p < 0.05). At
      this stage, cardiac parameters in SCH were similar to those of controls and were
      not affected by carvedilol administration. In 6-month-old SCH, 5-month
      administration of carvedilol decreased SBP from 102.16 +/- 3.61 to 90.60 +/- 2.80
      mm Hg (n = 5, p < 0.05), HR from 363 +/- 14 to 324 +/- 14 bpm (n = 5, p < 0.05),
      and LVESV from 0.18 +/- 0.01 to 0.13 +/- 0.01 ml/100 g BW (n = 5, p < 0.05), and
      increased EF and COI by 14 and 23%, respectively (n = 5, p < 0.05). The drug did
      not modify LVEDV or LVPWT. These results reveal that carvedilol significantly
      improves cardiac function in 6-month-old cardiomyopathic hamsters, but it does
      not prevent ventricular dilatation. Improved cardiac function appears to be
      secondary to decreased total peripheral resistance, due mainly to the vasodilator
      properties of the drug. Thus, overactivation of the sympathetic system is not
      likely to be a determining factor in the etiology of dilated cardiomyopathy in
      this animal model.

PMID- 17534125
TI  - Strychnine-sensitive glycine receptors mediate the analgesic but not hypnotic
      effects of emulsified volatile anesthetics.
AB  - The present study was designed to investigate the role of strychnine-sensitive
      glycine receptors in hypnosis and analgesia induced by emulsified volatile
      anesthetics. After having established the mice model of hypnosis and analgesia by
      intraperitoneally injecting (i.p.) appropriate doses of ether, enflurane,
      isoflurane or sevoflurane, we intracerebroventricularly (i.c.v.) or intrathecally
      (i.t.) injected different doses of strychnine and then observed the effects on
      the sleeping time using the awaken test and the pain index in hot-plate test
      (HPPI) using the hot-plate test. In the awaken test, strychnine 1, 2, 4 microg
      (i.c.v.) had no distinctive effect on the sleeping time of the mice treated with
      the four emulsified inhalation anesthetics mentioned above (p > 0.05); in the hot
      plate test, strychnine 0.1, 0.2, 0.4 microg (i.t.) can significantly and dose
      dependently decrease the HPPI of the mice treated with emulsified ether,
      enflurane and sevoflurane (p < 0.05, p < 0.01); strychnine 0.1 microg (i.t.) did
      not affect the HPPI of the mice treated with emulsified isoflurane (p > 0.05),
      but 0.2 and 0.4 microg (i.t.) can significantly decrease the HPPI of the mice
      treatedwith emulsified isoflurane (p < 0.05, p < 0.01). These results suggest
      that strychnine-sensitive glycine receptors may contribute to the analgesic but
      not to the hypnotic effects induced by ether, enflurane, isoflurane and
      sevoflurane.

PMID- 17534126
TI  - Protective effects of chronic lithium treatment against spatial memory retention
      deficits induced by the protein kinase AII inhibitor H-89 in rats.
AB  - We have previously shown that infusion of the PKAII inhibitor H-89 in the CA1
      area of the hippocampus impaired spatial memory retention. There is some evidence
      suggesting the neuroprotective effects of chronic lithium administration
      including its ability to attenuate a deleterious effect of chronic stress on
      spatial memory in rats. In the present study, we investigated whether chronic
      administration of lithium can improve memory as well as influence the inhibitory
      effect of H-89 on spatial memory retention. Male albino rats were treated
      systemically with lithium (600 mg/l) for 4 weeks and then trained for 4 days in
      the Morris water maze. Testing the animals 48 h later showed a significant
      reduction in escape latency (p < 0.05) and travel distance (p < 0.05) compared to
      the controls. In separate experiments, the rats were similarly treated with
      lithium for 4 weeks, followed by similar training for 4 days and then immediately
      infused bilaterally with vehicle or 5 micromol/l H-89 into the CA1 region of the
      hippocampus. Animals were then tested 48 h after H-89 infusion in order to assess
      their spatial memory retention. The lithium treatment caused a significant
      reduction in escape latency (p < 0.001) and travel distance (p < 0.001) compared
      to H-89-treated animals. The data suggest that lithium treatment for 4 weeks
      improved spatial memory retention and that lithium pretreatment prevented or
      reversed the H-89-induced spatial memory deficits.

PMID- 17534127
TI  - Cystic fibrosis and formes frustes of CFTR-related disease.
AB  - Cystic fibrosis (CF) is the commonest genetic cause of bronchiectasis in the
      Caucasian population. Since identification of the putative gene in 1989, the
      molecular basis of the condition has become clearer with characterisation of the
      unique pathophysiology. The small airways are the primary site of lung disease,
      with an intense but localised inflammatory picture, dominated by neutrophils. The
      clinical heterogeneity is explained to some degree by the distinct molecular
      consequences of the many mutations that have been recognised to affect the CF
      transmembrane conductance regulator (CFTR) gene; however other genes appear to
      modify the phenotype as well as environmental exposure. It has become
      increasingly apparent that certain conditions may result from CFTR dysfunction
      without fulfilling diagnostic criteria for CF. In some cases this may result in
      single organ disease for which the term CF (or CFTR)-related disease has been
      advocated. Congenital bilateral absence of the vas deferens is the most clearly
      characterised of these. In other cases where a mild CF phenotype is apparent,
      atypical CF is probably a better term. It remains unclear whether carrier status
      predisposes to certain conditions such as chronic rhinosinusitis or pancreatitis.

PMID- 17534128
TI  - Genetic causes of bronchiectasis: primary ciliary dyskinesia.
AB  - Primary ciliary dyskinesia (PCD) is a genetically heterogeneous disorder
      reflecting abnormalities in the structure and function of motile cilia and
      flagella, causing impairment of mucociliary clearance, left-right body asymmetry,
      and sperm motility. Clinical manifestations include respiratory distress in term
      neonates, recurrent otosinopulmonary infections, bronchiectasis, situs inversus
      and/or heterotaxy, and male infertility. Genetic discoveries are emerging from
      family-based linkage studies and from testing candidate genes. Mutations in 2
      genes, DNAI1 and DNAH5, frequently cause PCD as an autosomal recessive disorder.
      A clinical genetic test has been recently established for DNAI1 and DNAH5, which
      involves sequencing 9 exons that harbor the most common mutations. This approach
      will identify at least one mutation in these 2 genes in approximately 25% of PCD
      patients. If biallelic mutations are identified, the test is diagnostic. If only
      one mutation is identified, the full gene may be sequenced to search for a trans
      allelic mutation. As more disease-causing gene mutations are identified, broader
      genetic screening panels will further identify patients with PCD. Ongoing
      investigations are beginning to identify genetic mutations in novel clinical
      phenotypes for PCD, such as congenital heart disease and male infertility, and
      new associations are being established between 'ciliary' genetic mutations and
      clinical phenotypes.

PMID- 17534129
TI  - Genetic causes of bronchiectasis: primary immune deficiencies and the lung.
AB  - Primary immune deficiencies (PID) comprise a heterogeneous group of genetically
      determined disorders that affect development and/or function of innate or
      adaptive immunity. Consequently, patients with PID suffer from recurrent and/or
      severe infections that frequently involve the lung. While the nature of the
      immune defect often dictates the type of pathogens that may cause lung infection,
      there is substantial overlap of radiological findings, so that appropriate
      laboratory tests are mandatory to define the nature of the immune defect and to
      prompt appropriate treatment. At the same time, the recent identification of a
      large number of PID-causing genes now allows early, even presymptomatic
      diagnosis, thus representing an essential tool for prevention of lung damage.
      This review article describes the most common forms of PID, their cellular and
      molecular bases, and the associated lung abnormalities, and reports on available
      treatment.

PMID- 17534130
TI  - CPAP or APAP--what is the real question?

PMID- 17534131
TI  - The IS6110 repetitive DNA element of Mycobacterium tuberculosis is not detected
      in exhaled breath condensate of patients with active pulmonary tuberculosis.
AB  - BACKGROUND: A large tertiary referral hospital in inner-city Chicago. OBJECTIVES:
      To determine whether the IS6110 repetitive DNA element of Mycobacterium
      tuberculosis is detected in exhaled breath condensate of patients with newly
      diagnosed active pulmonary tuberculosis. METHODS: Ten hospitalized patients with
      positive Ziehl-Neelson-stained sputum smears were studied. Concurrent sputum
      cultures for mycobacteria were performed as well. Exhaled breath condensate was
      collected from each patient within 6 days of initiating antituberculosis
      chemotherapy (median 1.5 days). These samples were analyzed by polymerase chain
      reaction (PCR) using primers designed to amplify the IS6110 DNA fragment of M.
      tuberculosis. Exogenous M. tuberculosis DNA was added to exhaled breath
      condensate samples to detect PCR inhibitors. Concurrent cultures of exhaled
      breath condensate for mycobacteria were performed. RESULTS: M. tuberculosis was
      identified in 9 of 10 sputum cultures. One isolate was identified as
      Mycobacterium kansasii. The IS6110 repetitive DNA element of M. tuberculosis was
      not detected in any of the 10 exhaled breath condensate samples. Exogenous M.
      tuberculosis DNA added to these samples elicited the characteristic band pattern
      of M. tuberculosis on agarose gel electrophoresis. No PCR inhibitors were
      detected. Cultures of exhaled breath condensate showed no growth of mycobacteria.
      CONCLUSIONS: The IS6110 repetitive DNA element of M. tuberculosis is not detected
      in exhaled breath condensate of patients with newly diagnosed active pulmonary
      tuberculosis.

PMID- 17534132
TI  - The Economo-Koskinas atlas revisited: cytoarchitectonics and functional context.
AB  - The monumental Atlas of Cytoarchitectonics of the Adult Human Cerebral Cortex of
      Economo and Koskinas represents a gigantic intellectual and technical effort,
      never sufficiently recognized. One reason might have been the limited number of
      copies produced; another, the complex (albeit logical and precise) symbol
      notation, which comprises a Roman capital (from the initial of the respective
      lobe), a calligraphic capital (the sequence of a gyrus within a lobe), and a
      Latin or Greek subscript (for microscopic features). Economo and Koskinas defined
      107 cortical areas, as opposed to Brodmann's 44 areas for the human brain. Their
      cytoarchitectonic criteria confer the advantage of a more detailed parcellation
      scheme, despite the traditional familiarity of neuroscientists with Brodmann
      numbers. The system of 107 areas of Economo and Koskinas may be especially useful
      for modern studies on functional localization.

PMID- 17534133
TI  - A proposed number system for the 107 cortical areas of Economo and Koskinas, and
      Brodmann area correlations.
AB  - In their Atlas of Cytoarchitectonics of the Adult Human Cerebral Cortex, Economo
      and Koskinas defined 54 'ground,' 76 'variant,' and 107 'modification' areas. The
      107 modifications are topographically distributed as 35 frontal, 13 superior
      limbic, 6 insular, 18 parietal, 7 occipital, 14 temporal and 14 inferior limbic
      (or hippocampal). One way to make the Economo-Koskinas system more practical is
      to encode the complex symbol notations of the 107 cortical areas with numbers EK
      1 through EK 107. The present study does that, and it further correlates Economo
      Koskinas areas with Brodmann areas, based on an overview of the classical and
      modern neurohistological literature.

PMID- 17534134
TI  - A 12-month prospective study of gasserian ganglion stimulation for trigeminal
      neuropathic pain.
AB  - AIMS: Trigeminal neuropathic pain is a broad diagnostic category that includes
      pain of several etiologies and excludes trigeminal neuralgia. The authors report
      a prospective series of percutaneous gasserian ganglion stimulation for
      trigeminal neuropathic pain. METHODS: Patients who experienced >50% reduction in
      pain from a 7- to 10-day trial period underwent permanent implantation and were
      prospectively followed. RESULTS: Eight of 10 trialed patients received a
      permanent implant. At the 12-month follow-up, 2 patients had been explanted and 1
      was lost to follow-up. Three (all working at that the time) continued to
      experience >50% improvement in pain. DISCUSSION: The results in this series were
      variable but 3 patients showed long-term improvements. Patients who continued to
      work responded better to treatment.

PMID- 17534135
TI  - Effect of ventralis intermedius thalamotomy on the area in the sensorimotor
      cortex activated by passive hand movements: fMR imaging study.
AB  - Stereotactic ventralis intermedius (Vim) thalamotomy is effective for essential
      tremor (ET) of the limb, but the effect on the activity of the sensorimotor
      cortex is still unclear. The functional changes in this cortical area of patients
      with ET after Vim thalamotomy were investigated using functional magnetic
      resonance (fMR) imaging. Six patients underwent Vim thalamotomy for medically
      intractable ET, predominantly in the right hand. 1.5-tesla fMR imaging was
      performed using the blood oxygenation level-dependent sequence, before and after
      Vim thalamotomy, during passive movements with right wrist flexion and extension.
      Before and after images were analyzed using SPM99 software. Activation in the
      sensorimotor cortex and supplementary motor area evoked by wrist passive movement
      was observed both before and after surgery. Group analysis of changes in the
      blood oxygenation level-dependent response revealed a significantly smaller
      activated area postoperatively. Activation at the fundus of the central sulcus
      was characteristically decreased. All patients showed marked improvement in
      tremor after Vim thalamotomy. No patient experienced neurological deficits. fMR
      imaging showed that activation at the fundus of the central sulcus evoked by
      passive wrist movement was suppressed after Vim thalamotomy in ET patients,
      probably due to disruption of the thalamocortical pathway. The fundus of the
      central sulcus (Brodmann area 3a) is likely to be one of the key relays in the
      tremor circuit.

PMID- 17534136
TI  - Comparison of accuracy and precision between frame-based and frameless
      stereotactic navigation for deep brain stimulation electrode implantation.
AB  - The accuracy and precision of frameless neuronavigation as compared to
      conventional frame-based stereotaxy for implantation of deep brain stimulation
      (DBS) electrodes were studied in 14 patients with essential tremor. DBS
      electrodes were implanted bilaterally in the ventrolateral thalamus
      [ventrointermediate nucleus (VIM)] in one procedure. Frameless neuronavigation
      was used on one side and the conventional frame-based technique on the other.
      Targeting was guided by MRI and CT imaging. Intraoperative stereotactic plain X
      ray verified final electrode positions and electrode deviations from the planned
      target were measured. Clinical outcome was evaluated with the Essential Tremor
      Rating Scale. Thirteen of the patients were eligible for measuring electrode
      deviations and 10 of them were available for a clinical follow-up. Electrode
      deviations from target were larger using the frameless technique in the medial
      lateral (x: 1.9 +/- 1.3 mm) and anterior-posterior (y:0.9 +/- 0.8 mm) directions
      as compared to the frame-based technique (x: 0.5 +/- 0.5 and y: 0.4 +/- 0.4 mm)
      but similar in the superior-inferior direction (z). The vector of deviation was
      2.5 +/- 1.4 mm with the frameless technique and 1.2 +/- 0.6 with the frame-based
      technique. The differences were statistically significant (p < 0.05-0.001). The
      dispersion was larger with the frameless technique as represented by the larger
      standard deviations in all three planes. At clinical follow-ups, tremor reduction
      was similar irrespective of the implantation technique. It is concluded that
      conventional frame-based stereotaxy has higher accuracy/precision for hitting a
      small brain target than the frameless technique. However, the difference is
      relatively small and does not influence the clinical result of DBS electrode
      implantations in the VIM when treating tremor.

PMID- 17534137
TI  - Placement of intraventricular catheters using flexible electromagnetic navigation
      and a dynamic reference frame: a new technique.
AB  - BACKGROUND: Catheterization of narrow ventricles may prove difficult resulting in
      misplacement or inefficient trials with potential damage to brain tissue.
      MATERIAL AND METHODS: The application of a new module for navigated ventricular
      catheterization using flexible electromagnetic navigation and a dynamic reference
      frame is presented. RESULTS: Navigated catheter placement was successful and
      accurate in a pilot study. Electromagnetic interferences had to be taken into
      consideration. CONCLUSION: Flexible electromagnetic navigation with a dynamic
      reference frame is a useful tool for catheter placement as it reduces the risk of
      misplacement or repeated catheterization trials.

PMID- 17534138
TI  - A new mechatronic assistance system for the neurosurgical operating theatre:
      implementation, assessment of accuracy and application concepts.
AB  - OBJECTIVE: To introduce a new robotic system to the field of neurosurgery and
      report on a preliminary assessment of accuracy as well as on envisioned
      application concepts. Based on experience with another system (Evolution 1, URS
      Inc., Schwerin, Germany), technical advancements are discussed. MATERIAL/METHODS:
      The basic module is an industrial 6 degrees of freedom robotic arm with a
      modified control element. The system combines frameless stereotaxy, robotics, and
      endoscopy. The robotic reproducibility error and the overall error were
      evaluated. For accuracy testing CT markers were placed on a cadaveric head and
      pinpointed with the robot's tool tip, both fully automated and telemanipulatory.
      Applicability in a clinical setting, user friendliness, safety and flexibility
      were assessed. RESULTS: The new system is suitable for use in the neurosurgical
      operating theatre. Hard- and software are user-friendly and flexible. The mean
      reproducibility error was 0.052-0.062 mm, the mean overall error was 0.816 mm.
      The system is less cumbersome and much easier to use than the Evolution 1.
      CONCLUSIONS: With its user-friendly interface and reliable safety features, its
      high application accuracy and flexibility, the new system is a versatile robotic
      platform for various neurosurgical applications. Adaptations for different
      applications are currently being realized.

PMID- 17534139
TI  - Dissection of the autophagosome maturation process by a novel reporter protein,
      tandem fluorescent-tagged LC3.
AB  - During the process of autophagy, autophagosomes undergo a maturation process
      consisting of multiple fusions with endosomes and lysosomes, which provide an
      acidic environment and digestive function to the interior of the autophagosome.
      Here we found that a fusion protein of monomeric red-fluorescence protein and
      LC3, the most widely used marker for autophagosomes, exhibits a quite different
      localization pattern from that of GFP-LC3. GFP-LC3 loses fluorescence due to
      lysosomal acidic and degradative conditions but mRFP-LC3 does not, indicating
      that the latter can label the autophagic compartments both before and after
      fusion with lysosomes. Taking advantage of this property, we devised a novel
      method for dissecting the maturation process of autophagosomes. mRFP-GFP tandem
      fluorescent-tagged LC3 (tfLC3) showed a GFP and mRFP signal before the fusion
      with lysosomes, and exhibited only the mRFP signal subsequently. Using this
      method, we provided evidence that overexpression of a dominant negative form of
      Rab7 prevented the fusion of autophagosomes with lysosomes, suggesting that Rab7
      is involved in this step. This method will be of general utility for analysis of
      the autophagosome maturation process.

PMID- 17534140
TI  - Macroautophagy: protector in the diabetes drama?
AB  - Macroautophagy ("autophagy") is regulated by the same insulin-amino acid-mTOR
      signaling pathway that controls protein synthesis. Although the literature does
      not so far include any direct studies confirming this, we expect autophagy to
      increase during insulin resistance. We discuss the possibility that this may be a
      useful mechanism for eliminating damaged mitochondria and other cell structures
      to prevent cell death.

PMID- 17534141
TI  - Autophagy and vacuole homeostasis: a case for self-degradation?
AB  - The vacuole of yeast plays an important role in pH- and ion-homeostasis. Another
      important function of the vacuole, especially during nutrient deprivation, is the
      degradation of proteins, other macromolecules and organelles. To deliver these
      components into the vacuolar lumen, specific and sophisticated transport pathways
      such as autophagy have evolved. This review will first look at autophagy and its
      relationship to vacuole homeostasis, then move to the topic of vacuole self
      degradation and possible reasons for its existence, and close by pointing very
      briefly to some areas for further research in these topics.

PMID- 17534142
TI  - P53 dependent and independent apoptosis induced by lidamycin in human colorectal
      cancer cells.
AB  - Enediyne compound is one class of antibiotics with very potent anti-cancer
      activity. However, the role of p53 in enediyne antibiotic-induced cell killing
      remains elusive. Here we reported the involvement of p53 signaling pathway in
      apoptosis induction by lidamycin (LDM), a member of the enediyne antibiotic
      family. We found that LDM at low drug concentration of 10 nmol/L induces
      apoptotic cell death much more effectively in human colorectal cancer cells with
      wild type p53 than those with mutant or deleted p53. p53 is functionally
      activated as an early event in response to low dose LDM that precedes the
      significant apoptosis induction. The primarily activation of mitochondria as well
      as the activation of p53 transcriptional targets such as Puma, Bad and Bax in
      HCT116 p53 wild type cells further demonstrates the key role of p53 in mediating
      the compound-induced apoptosis. This is further supported by the observation that
      the absence of Bax or Puma decreases apoptosis dramatically while Bcl-2
      overexpression confers partially resistance after drug treatment. Activation of
      p53 signaling pathway leads to activation of caspases and caspases inhibitor VAD
      fmk completely blocks low dose LDM induced apoptosis through the inhibition of
      mitochondria pathway. In contrast, LDM at higher concentration causes rapid
      apoptosis through more direct DNA damaging mechanism that is independent of
      activation of p53 and caspases and cannot be blocked by caspase inhibitor. Taken
      together, LDM induces apoptosis in a p53-dependent manner when given at low
      doses, but in a p53-independent manner when given at high doses. This dosage
      dependent regimen can be applied to cancer clinic based upon the p53 status of
      cancer patients.

PMID- 17534143
TI  - Cationic lipid complexed camptothecin (EndoTAG-2) improves antitumoral efficacy
      by tumor vascular targeting.
AB  - Neo-vascular targeting by cationic colloidal carriers enables to realize an
      innovative approach for tumor therapy. EndoTag-2 is a novel vascular targeting
      agent, comprising the mammalian topoisomerase I inhibitor camptothecin in its
      carboxylate form complexed to cationic lipid (cationic lipid complexed
      camptothecin). Here we studied tumor vascular targeting properties, antitumoral
      effects and mode of action of EndoTag-2. Tumor vascular targeting properties of
      fluorescently labelled EndoTag-2 were investigated by in vivo microscopy using A
      MEL-3 tumors grown in the dorsal skinfold chamber preparation and by fluorescence
      histology of s.c. LLC-1 carcinomas. Therapeutic effects have been investigated in
      the s.c. LLC-1 carcinoma model and the L3.6pl human pancreatic cancer model
      implanted orthotopically in athymic nude mice. Antivascular effects have been
      studied by histological investigation of tumor microvessel density and non
      invasive investigation of tumor blood flow by dynamic contrast enhanced MRI
      imaging (DCE-MRI). EndoTag-2 selectively targeted tumor microvessels as confirmed
      by quantitative fluorescence microscopy. Compared to controls EndoTag-2 revealed
      remarkable antitumoral efficiency in s.c. LLC-1 carcinomas implanted in C57/Bl6
      mice. Growth and metastasis of orthotopic L3.6pl human pancreatic tumors was
      significantly inhibited by EndoTag-2 treatment. Quantitative analysis of tumor
      microvessel density revealed significant reduction of microvessel density in
      lewis lung carcinomas up to 50%. DCE-MRI confirmed significant reduction of
      intratumoral vascular volume as well as tumor perfusion upon EndoTag-2 treatment.
      In conclusion this study shows that cationic lipid complexed camptothecin
      (EndoTag-2) is a markedly active antitumor agent based on an innovative vascular
      targeting approach.

PMID- 17534144
TI  - The pathology of tumor stromatogenesis.
AB  - Stromatogenesis is the formation of new, specific type, stroma at sites of active
      tumor cell invasion as an integral part of the invading process. The newly formed
      stroma by being wedged between tissue planes of least resistance disrupts the
      continuity of normal structures cleaving paths for the invading tumor cells-
      intramural stromatogenesis for endophytic tumors. Less frequently, the new stroma
      is formed towards a void space, i.e. at the free surfaces, whether internal or
      external (extramural stromatogenesis for exophytic tumors). It is postulated that
      the formation of this new stroma is generated and governed by the invading tumor
      cells with the tolerance and complicity of the adjacent activated fibroblasts.
      The spindle cells of the "neostroma" are intensely proliferating myofibroblasts,
      which are characterized by the frequent expression of alpha-smooth muscle actin
      and the particularly frequent expression of thymidine phosphorylase, PDGF
      receptors and SPARC (secreted protein acidic rich in cysteine). The cellular and
      extracellular qualities, different as they are from those of reactive fibrosis,
      make stromatogenesis amenable to easy penetration by neoplastic cells and a
      prospective method for diagnosing early tumor invasion. Studies also suggest that
      the neostroma has complementary to cancer cell metabolic activity, important for
      buffering of cancer cell waste products and for the prevention of cancer cell
      acidic death. Thus, cancer cells and neostroma should not be seen as a mixture of
      heterogeneous uncoordinated cells but rather as a unified morphologic and
      metabolic domain with a harmonious collaboration between aerobic (myofibroblasts,
      endothelial cells) and anaerobic compartments (cancer cells).

PMID- 17534145
TI  - In vitro efficacy of immuno-chemotherapy with anti-EGFR human Fab-Taxol conjugate
      on A431 epidermoid carcinoma cells.
AB  - The aims of this study were to generate a human Fab fragment against EGFR;
      conjugate it to paclitaxel (Taxol) as an immuno-chemotherapy agent; and
      investigate its in vitro anti-tumor efficacy on A431 epidermoid carcinoma cells.
      A431 cells (EGFR-positive), NIH 3T3 cells (EGFR-negative), and purified EGFR were
      used for subtractive panning on a human naive Fab phage library to generate a
      human anti-EGFR Fab fragment that binds the EGFR extracellular domain in native
      conformation and subsequently internalizes it into the cytosol. The Fab was then
      conjugated with the chemotherapeutic Taxol, and cell proliferation inhibition and
      apoptosis (TUNEL) assays were conducted to determine the effect of this Fab-drug
      conjugate on A431 cells. The specificity and internalization property of this Fab
      were characterized by immunoprecipitation, fluorescence staining, flow cytometry,
      and Hum-Zap assay. The binding affinity to purified EGFR was 30 nM. The Fab-Taxol
      conjugate inhibited A431 cell proliferation at low concentrations and in a dose
      responsive manner; more than 70% inhibition was observed at 52 pM. Furthermore,
      almost 100% of cells underwent apoptosis after treatment with Fab-Taxol at 26 pM
      for 48 hours. Our findings suggest that this Fab-Taxol conjugate could be a
      potential immuno-chemotherapeutic drug for clinical treatment of EGFR
      overexpressing tumors.

PMID- 17534146
TI  - Posttranscriptional orchestration of an anti-apoptotic program by HuR.
AB  - The RNA-binding protein HuR can stabilize and/or regulate the translation of
      target mRNAs, thereby affecting the cellular responses to immune, proliferative,
      and damaging agents. Here, we discuss emerging evidence that HuR elicits a broad
      anti-apoptotic function through its influence on the expression of multiple
      target mRNAs. HuR was previously shown to bind to the mRNA encoding the
      apoptosome inhibitor prothymosin a(ProT alpha) and enhanced its translation and
      cytoplasmic abundance. More recently, HuR was shown to increase the stability of
      a target mRNA encoding the pro-survival deacetylase SIRT1. The discovery that HuR
      likewise binds to and promotes the expression of mRNAs encoding Bcl-2 and Mcl-1,
      two major anti-apoptotic effectors, strongly supports HuR's role as a key
      upstream coordinator of a constitutive pro-survival program.

PMID- 17534147
TI  - Soothing the watchman: telomerase reduces the p53-dependent cellular stress
      response.
AB  - In addition to conferring an indefinite replicative life span, telomerase renders
      p16(-) human mammary epithelial cells (HMEC) resistant to growth arrest by
      TGFbeta or by loss of EGF or insulin signaling. In contrast to earlier reports,
      we recently found that growth factor signaling was not directly affected by
      telomerase expression. Rather, short dysfunctional or near-dysfunctional
      telomeres in proliferating telomerase(-) HMEC sensitized the cells to p53
      dependent signals for growth arrest. We showed that during serial passage and
      before any signs of replicative senescence, HMEC lacking telomerase experience
      enhanced p53 stability and DNA damage signaling, as determined by increased
      phosphorylation on p53-Ser15 and Chk2-Thr68, and formation of
      53BP1/phosphorylated histone H2AX foci at chromosome ends. This heightened
      activity of the p53 pathway enhanced the efficiency with which cells arrested
      growth in response to TGFbeta or to EGF or insulin withdrawal, and was abolished
      by ectopic expression of hTERT, the catalytic subunit of telomerase. Telomerase
      elongated short telomeres, thereby reducing the basal level of activated p53 and
      raising cellular tolerance for other p53-dependent signals, including those
      emanating from non-genotoxic sources. These findings explain a number of observed
      effects of telomerase expression on cell growth and survival without postulating
      additional functions for telomerase.

PMID- 17534148
TI  - TGF-beta receptor I conditional knockout mice develop spontaneous squamous cell
      carcinoma.
AB  - We generated a mouse model with a conditional deletion of TGF-beta signaling in
      the neurons by crossing TGF-beta receptor I (TbetaRI) floxed mice with
      neurofilament-H (NF-H) Cre mice. 35% of F1 conditional knockout (COKO) mice
      developed spontaneous squamous cell carcinomas (SCCs) in periorbital and/or
      perianal regions. Transplantation of these tumors into athymic nude mice resulted
      in 62% tumorigenicity. To determine whether evasion of the immune response plays
      any role in this tumorigenesis, we analyzed the expression levels of receptors
      for interleukin-13 (mIL-13R), a key negative regulator of tumor
      immunosurveillance, and found that 33% of COKO tumors expressed the IL-13R alpha2
      chain. Primary cultures of the SCCs expressing IL-13R alpha2 were sensitive to
      the cytotoxic effect of IL-13R-directed cytotoxin treatment. This is the first
      demonstration that loss of TbetaRI can lead to spontaneous tumor formation. These
      mice can serve as a unique mouse model of SCC to evaluate the tumorigenicity and
      effect of anti-cancer therapeutics.

PMID- 17534149
TI  - The ARF/oncogene pathway activates p53 acetylation within the DNA binding domain.
AB  - Stabilization of the p53 tumor suppressor is a critical event in the response to
      various forms of cellular stress. Two distinct signaling pathways are thought to
      lead to this stabilization, depending on the type of cellular stress encountered.
      Genotoxic stress, such as chromosomal breaks or lesions induced by
      chemotherapeutic agents, result in the activation of the well-characterized DNA
      damage response pathway. Conversely, cellular stress that results from the
      aberrant activation of oncogenes triggers p53 stabilization via the induction of
      the p19ARF pathway. While activation of the DNA damage pathway ultimately causes
      a complex array of post-translational modifications on p53, few if any
      modifications have been demonstrated to occur following activation of the p19ARF
      pathway. We and others have recently identified a novel modification on p53,
      acetylation of lysine 120 within the DNA binding domain. This acetylation event
      is eliminated by tumor-derived mutations in p53 and its presence is required for
      the tumor suppressor apoptotic function of p53. We demonstrate here that both the
      DNA damage response pathway and the p19ARF/oncogene stress pathway induce the
      acetylation of p53 at lysine 120.

PMID- 17534150
TI  - Genetic deficiency of p38alpha reveals its critical role in myoblast cell cycle
      exit: the p38alpha-JNK connection.
AB  - The regulation of skeletal muscle formation (myogenesis) is essential for normal
      development as well as in pathological conditions such as muscular dystrophies
      and inflammatory myopathies. Findings published over the past years have
      established a key role for the p38 MAP kinase signaling pathway in the control of
      muscle gene expression and myotube formation. However, the relative contribution
      of the four p38 MAP kinases (p38alpha, p38beta, p38gamma and p38delta) to this
      process was unknown. We have recently demonstrated that myoblasts lacking
      p38alpha, but not those lacking p38beta or p38delta, were unable to differentiate
      and form multinucleated myotubes, while p38gamma-deficient myoblasts exhibited an
      attenuated fusion capacity. Defective myogenesis in the absence of p38alpha was
      attributed to delayed cell cycle exit and continuous proliferation in
      differentiation-promoting conditions, caused by enhanced activation of the
      JNK/cJun pathway. We discuss these findings in the context of the emerging
      crosstalk of p38 and JNK signaling pathways in controlling cell growth and
      differentiation.

PMID- 17534151
TI  - Circadian clock and breast cancer: a molecular link.
AB  - The circadian clock controls a large array of behavioral and physiological
      systems of fundamental importance to most organisms. Consequently, abnormal
      functioning of the clock results in severe dysfunctions and pathologies. Although
      epidemiological studies show a clear correlation between disruption of circadian
      rhythms and incidence of breast cancer, a molecular interpretation of how clock
      related mechanisms may link to tumor development remains elusive. Here we
      speculate on the molecular pathways that may couple the circadian machinery to
      breast cancer.

PMID- 17534152
TI  - ASPM and citron kinase co-localize to the midbody ring during cytokinesis.
AB  - Mutations in ASPM (abnormal spindle-like microcephaly associated) and citron
      kinase (CITK) cause primary microcephaly in humans and rodents, respectively.
      Both proteins are expressed during neurogenesis and play important roles in
      neuronal progenitor cell division. ASPM is localized to the spindle pole, and is
      essential for maintaining proliferative cell division. CITK is present at the
      cytokinesis furrow and midbody ring, and it is essential for cellular abscission.
      We report here that ASPM also localizes to the midbody ring in mammalian cells.
      ASPM co-localizes with CITK at the midbody ring and coimmunoprecipitates with
      CITK in lysates prepared from HeLa cells and embryonic neuroepithelium.
      Furthermore, a GFP-tagged fragment of the N-terminus of ASPM localizes to
      centrosomes and spindle poles, while a GFP-tagged fragment of the C-terminus
      localizes to midbodies. All reported ASPM mutations that cause microcephaly
      involve a truncation or mutation of the C-terminus. In addition, at least two
      other microcephaly-related proteins, CENPJ and CDK5RAP2, previously localized to
      spindle poles, also localize to midbodies. Together our observations support a
      model of neurogenesis in which spindle dynamics and cellular abscission are
      coordinated.

PMID- 17534154
TI  - Transcriptional networks regulating hematopoietic cell fate decisions.
AB  - PURPOSE OF REVIEW: We provide a summary of the temporal cascade of
      transcriptional networks giving rise to the hematopoietic stem cell (HSC) and
      controlling differentiation of the erythroid lineage from it. We focus on the
      mechanisms by which cell fate decisions are made and comment on recent
      developments and additions to the networks. RECENT FINDINGS: A role for an
      SCL/LMO2 complex in HSC emergence, as well as in subsequent erythroid
      differentiation, has received support. Connections between the transcriptional
      networks and signaling molecules are being made but more work is needed in this
      area. Evidence that transcriptional cross-antagonistic switches underlie the
      choice between lineage pathways is increasing, and we highlight how the dynamics
      of earlier lineage decisions can influence later ones. Mathematical models are
      being built and reveal a surprising degree of power in these simple motifs to
      explain lineage choices. SUMMARY: New links in the transcriptional networks
      underlying cell-fate decisions are constantly emerging, and their incorporation
      into the evolving networks will make mathematical modeling more precise in its
      predictions of cell behavior, which can be tested experimentally.

PMID- 17534156
TI  - Regulatory factors for initial T lymphocyte lineage specification.
AB  - PURPOSE OF REVIEW: Initiation of T lymphocyte development depends on balanced
      regulatory inputs from multiple essential transcription factors. This review
      highlights contributions of E2A, hematopoietic transcription factor PU.1, growth
      factor independence (Gfi)-1, T cell factor (TCF)-1, and Runx factors and their
      interactions with the Notch pathway to promote T cell development. RECENT
      FINDINGS: E2A and Runx family factors have been implicated in establishing
      competent precursors in which Notch signaling can induce the T cell program. An
      early role was also indicated for PU.1. Later PU.1 activities are antagonistic to
      pro-T cell factors, however, including E proteins, Myb, Gfi-1, and TCF-1.
      Diversion to a non-T lineage can be promoted by PU.1, CCAAT/enhancer binding
      protein, or even GATA and TCF, but these diversion mechanisms are blocked by
      Notch signaling. An emergent gene network summarizes the cross-regulatory
      relationships among these factors. SUMMARY: Entry into the T-cell pathway is
      controlled by a dynamic balance among essential regulatory factors that depend on
      Notch signaling not only to trigger initiation of the T-cell program but also to
      maintain the lineage fidelity of their collective action.

PMID- 17534155
TI  - Delineation of the earliest lineage commitment steps of haematopoietic stem
      cells: new developments, controversies and major challenges.
AB  - PURPOSE OF REVIEW: This review addresses recently reported evidence for
      alternative cellular pathways for haematopoietic stem cell lineage commitment.
      RECENT FINDINGS: Using various approaches, several laboratories suggested the
      existence of adult as well as foetal multipotent progenitor cells with combined B
      cell, T cell and granulocyte/macrophage potential, but little or no
      megakaryocyte/erythroid potential. Compared with haematopoietic stem cells, these
      multipotent progenitor cells exhibited downregulated transcriptional expression
      of genes of the megakaryocyte/erythroid lineages and upregulated expression of
      lymphoid lineage genes. The existence of these lineage-restricted multipotent
      progenitor cells suggests that the first lineage commitment step of
      haematopoietic stem cells does not result in strict separation into myelopoiesis
      and lymphopoiesis, and that there might be alternative pathways for commitment
      toward different lineage fates. These findings have been questioned by other
      studies, however. To resolve this controversy and establish the complete road map
      for haematopoietic lineage commitment, improved tools and more stringent
      standards for how to identify and characterize lineage fate options of distinct
      stem and progenitor cells are needed. SUMMARY: Current and future progress in
      establishing the complete cellular roadmap for haematopoietic lineage commitment
      will permit identification and characterization of key regulators of lineage fate
      decisions in haematopoietic stem cells.

PMID- 17534157
TI  - The beauty of asymmetry: asymmetric divisions and self-renewal in the
      haematopoietic system.
AB  - PURPOSE OF REVIEW: The hallmark of stem cells is their dual abilities to self
      renew and to differentiate into multiple lineages. To fulfill these functions
      they must undergo asymmetric division. A central question in developmental
      biology is how can a single cell divide to produce two progeny cells that adopt
      different fates? We provided evidence of the significance of asymmetric division
      in human haematopoietic stem cells. RECENT FINDINGS: By monitoring the symmetry
      of divisions of haematopoietic stem cells and following their subsequent
      developmental potentials at the single cell level, we established a relationship
      between divisional kinetics and self-renewal capacity. Direct cell-cell contact
      with cellular determinants in the niche has been shown to play an essential role
      in maintaining stemness. The creation of in-vitro models for the niche, such as
      human mesenchymal stromal cells, has provided a controlled laboratory environment
      in which the relative significance of chemokines and adhesion molecules can be
      studied. SUMMARY: Identification of the molecular interactions between stem cells
      and their niche has led to an understanding of the mechanisms that control the
      self-renewal of stem cells. Ultimately, molecular signals triggered by adhesion
      and junction complexes are responsible for the adoption of specific cell fate.

PMID- 17534158
TI  - Insertional mutagenesis in gene therapy and stem cell biology.
AB  - PURPOSE OF REVIEW: Recent preclinical and clinical studies revealed that the
      semirandom insertion of transgenes into chromosomal DNA of hematopoietic cells
      may induce clonal competition, which potentially may even trigger leukemia or
      sarcoma. Insertional mutagenesis caused by gene vectors has thus led to major
      uncertainty among those developing advanced hematopoietic cell therapies. This
      review summarizes novel studies of underlying mechanisms; these studies have
      demonstrated the possibility of improved gene vector biosafety and generated new
      insights into stem cell biology. RECENT FINDINGS: The characteristic insertion
      pattern of various retroviral gene vector systems may be explained by properties
      of the viral integrase and associated cellular cofactors. Cell culture assays and
      animal models, including disease-specific and cancer-prone mouse models, are
      emerging that reveal the contributions of vector features and systemic factors to
      induction of clonal imbalance. Databases summarizing vector insertion sites in
      dominant hematopoietic clones are evolving as new tools to identify genes that
      regulate clonal homeostasis. SUMMARY: Mechanistic studies of insertional
      mutagenesis by random gene vector insertion will lead to improved tools for
      advanced hematopoietic cell therapy. Simultaneously, fascinating insights into
      gene networks that regulate cell fitness will be generated, with important
      consequences for the fields of hematology, oncology and regenerative medicine.

PMID- 17534159
TI  - Towards hematopoietic reconstitution from embryonic stem cells: a sanguine
      future.
AB  - PURPOSE OF REVIEW: To review recent progress towards the derivation of
      hematopoietic stem cells (HSCs) and blood lineages from embryonic stem cells
      (ESCs), and to highlight the hurdles that must be overcome in order to move the
      field closer to a clinical application. RECENT FINDINGS: Hematopoietic
      repopulating cells, red blood cells, and T cells have recently been derived from
      both murine and human ESCs. Although these results are encouraging, several
      outstanding issues remain to be addressed by the field before realizing clinical
      applicability: the phenotype of the ESC-derived HSC must be characterized,
      methods to purge residual teratoma-forming cells from differentiated populations
      must be established, and in-vivo models of human HSC function must be optimized
      to better assess the functionality of putative human ESC-derived HSCs. In
      addition, embryonic stem-cell derived progeny often represent primitive embryonic
      hematopoietic cells, rather than their definitive adult counterparts; this
      critical issue must also be addressed. SUMMARY: The literature firmly establishes
      that it is possible to isolate HSCs and certain mature blood lineages from both
      mouse and human ESCs. Although several issues remain to be addressed, these data
      demonstrate the value of ESCs as a potential source of transplantable HSCs.

PMID- 17534160
TI  - Angioimmunoblastic T cell lymphoma: pathobiological insights and clinical
      implications.
AB  - PURPOSE OF REVIEW: Angioimmunoblastic T cell lymphoma is a complex
      lymphoproliferative disorder. While recent evidence suggests that the Epstein
      Barr virus and B cell disregulation are implicated in the disease's pathogenesis,
      their mechanistic roles remain largely unknown. The prognosis with traditional
      chemotherapy has been poor, but improved understanding of the disease's
      pathobiology has led to several promising novel therapeutic strategies. RECENT
      FINDINGS: The recent finding of overexpression of the chemokine CXCL13 by the
      neoplastic cells of angioimmunoblastic T cell lymphoma suggests that it is
      derived from follicular helper T cells. In addition, gene-expression profiling
      has demonstrated overexpression of several genes characteristic of follicular
      helper T cells. Vascular endothelial growth factor-A is also highly expressed.
      Novel therapeutic strategies including immunomodulation with agents like
      cyclosporine and angiogenesis inhibition with drugs such as bevacizumab are being
      investigated, and show early promise in this disease. SUMMARY: Diseases such as
      angioimmunoblastic T cell lymphoma can help illuminate the biology of the normal
      immune system. Significant progress has been made in understanding the biology of
      angioimmunoblastic T cell lymphoma. This has paved the way for the development of
      new therapeutic strategies and these have shown interesting results.

PMID- 17534161
TI  - Castleman disease.
AB  - PURPOSE OF REVIEW: Castleman disease was initially described over 50 years ago as
      a benign localized mass of lymph nodes found primarily in the mediastinum of
      asymptomatic patients. Subsequently, additional types were recognized that extend
      the spectrum of this heterogeneous group of diseases. Optimal standard therapies
      have not been established. Currently, most patients receive treatments derived
      from past experience with non-Hodgkin lymphoma that are not altogether
      satisfactory. RECENT FINDINGS: Advances in understanding the biological basis of
      Castleman disease have provided new targets for therapeutic exploitation.
      Recognition of the role of interleukin-6 in disease perpetuation has led to the
      use of an antihuman interleukin-6 receptor monoclonal antibody, tocilizumab.
      Rituximab, an anti-CD20 monoclonal antibody, targets CD20-positive B lymphocytes,
      a prominent component of this disorder. Human herpes virus-8 and angiogenesis,
      both involved in the pathogenesis of Castleman disease, may provide additional
      unique therapeutic opportunities. SUMMARY: Rational approaches to the treatment
      of Castleman disease have begun to have an impact on disease management; however,
      the role of these new agents remains to be established. As the complexity of
      Castleman disease is more fully understood, additional targets for new innovative
      therapies undoubtedly will be identified.

PMID- 17534162
TI  - Defining the role of immunotherapy and radioimmunotherapy in the treatment of low
      grade lymphoma.
AB  - PURPOSE OF REVIEW: To critically assess recent advances in the treatment of
      indolent non-Hodgkin lymphoma with a focus on immunologically based therapies.
      RECENT FINDINGS: Modern treatment strategies, including monoclonal antibodies
      targeting lymphoma-associated antigens, radioimmunotherapy, therapeutic
      vaccination and allogeneic hematopoietic stem cell transplantation, have the
      potential to profoundly impact clinical outcomes in indolent lymphoma therapy.
      The results of randomized phase III trials now indicate that the addition of
      rituximab to combination chemotherapy prolongs progression-free and overall
      survival compared to chemotherapy alone. It is anticipated that similar
      improvements in outcomes will be associated with other immunologic strategies.
      SUMMARY: Many questions remain unanswered regarding the optimal treatment
      approach for patients with indolent lymphoma. Randomized phase III trials
      addressing the key issues in patient management are ongoing. Continued follow-up
      of treated patients will be required to assess the character and frequency of
      long-term toxicities, and to provide insights into the best sequencing of
      treatments. It is likely that combinations of new treatment strategies will have
      the greatest impact on long-term clinical outcome. New insights into the
      underlying biology of the indolent lymphomas are anticipated to help guide
      therapy for individual patients and to provide new therapeutic targets.

PMID- 17534163
TI  - Genomics and proteomics in multiple myeloma and Waldenstrom macroglobulinemia.
AB  - PURPOSE OF REVIEW: Multiple myeloma and Waldenstrom macroglobulinemia are
      incurable hematologic malignancies with similar clinical phenotypes characterized
      by over-production of monoclonal immunoglobulins. Translocations into the
      immunoglobulin heavy chain locus and aneuploidy are nearly universal in multiple
      myeloma, whereas Waldenstrom macroglobulinemia generally does not harbor
      translocations. Deletion of 6q is identified in 50% of patients with Waldenstrom
      macroglobulinemia, however. The genetic abnormalities in multiple myeloma and
      Waldenstrom macroglobulinemia have implications for disease progression, and the
      subsequent proteomic expression associated with each disease influences
      therapeutic decisions. RECENT FINDINGS: Gene expression profiling in these
      hematologic malignancies demonstrated distinct differences in mRNA expression
      patterns. Following profiling, Waldenstrom macroglobulinemia samples clustered
      with chronic lymphocytic leukemia and normal B-cell samples. Profiling performed
      after separation of Waldenstrom macroglobulinemia samples into populations with
      plasma cell or B-cell morphology revealed that plasma cell Waldenstrom
      macroglobulinemia samples most closely resembled multiple myeloma samples rather
      than chronic lymphocytic leukemia or normal control samples. SUMMARY: Diverse
      genetic abnormalities have been identified in these hematologic malignancies,
      although they have similar clinical features. Gene expression profiling has
      elucidated the impact of genetic abnormalities. Furthermore, it may be used to
      identify a specific pathway for therapeutic targeting, such as interleukin-6 in
      Waldenstrom macroglobulinemia.

PMID- 17534164
TI  - Biology and treatment of Burkitt's lymphoma.
AB  - PURPOSE OF REVIEW: Burkitt's lymphoma is a unique hematological malignancy
      remarkable for its biological characteristics, including aberrant expression of
      the MYC oncogene, and its requirement for intensive treatment regimens. This
      review will focus on those features, and discuss recent advances in the molecular
      biology and advancing treatment options for the disease. RECENT FINDINGS:
      Advances in molecular biology have provided many new insights into the biology
      and treatment options for Burkitt's lymphoma. Microarray technology has recently
      been used to define a molecular gene expression signature for Burkitt's lymphoma.
      This signature allows for the differentiation of Burkitt's lymphoma from other
      forms of non-Hodgkin's lymphoma such as diffuse large B-cell lymphoma. Recent
      advances in the use of biological agents, such as rituximab, have also allowed
      for a reduction in treatment toxicities while still offering comparable survival
      outcomes for patients. SUMMARY: Burkitt's lymphoma is an interesting mature B
      cell non-Hodgkin's lymphoma that has numerous distinct features and clinical
      variants depending on factors such as geographical location, immunological status
      and patient's age. Although the role of the MYC oncogene has been well studied,
      we are only now appreciating the defining molecular characteristics of this
      disease, and using these advances to improve treatment options for patients.

PMID- 17534165
TI  - Bibliography. Current world literature. Hematopoiesis.

PMID- 17534167
TI  - Lung cancer screening: has there been any progress? Computed tomography and
      autofluorescence bronchoscopy.
AB  - PURPOSE OF REVIEW: Advances in imaging technologies are currently being explored
      in the attempt to reduce lung cancer morbidity and mortality by achieving stage
      shift. We reviewed recent important publications on lung cancer screening. RECENT
      FINDINGS: Autofluorescence bronchoscopy has established its important role in the
      intervention of early central airway lesions. Multidetector computed tomography
      (CT) and CT-positron emission tomography may facilitate diagnosis of early
      parenchymal lung lesions. Practical implications of screening are reaching far
      beyond early diagnostic efforts per se as lead-time, length-time, overdiagnosis
      biases combined with low specificity of screening tests undermine its cost
      effectiveness in the era of healthcare budget constraints. SUMMARY: Advanced
      imaging technologies may allow early detection and prudent intervention in some
      individuals that harbour asymptomatic early lung cancer, but disproportional
      expenses may be required to sieve out many more individuals at risk to attain
      stage shift. Confounding co-morbidities and practical hurdles may reduce
      screening's efficacy as it is plausible that for the majority of smokers, lung
      cancer may not be the ultimate cause of suffering since 90% of them will not
      develop lung cancer. This fact remains true despite increased use of noninvasive
      and minimally invasive technologies for the maximum preservation of quality of
      life irrespective of whether early intervention is a success or failure.

PMID- 17534168
TI  - Biomarkers for lung cancer: clinical uses.
AB  - PURPOSE OF REVIEW: Biomarkers for lung cancer may be used for risk
      stratification, early detection, treatment selection, prognostication and
      monitoring for recurrence. All these areas of clinical management would benefit
      from sensitive and specific, noninvasive, cost-effective biomarkers. RECENT
      FINDINGS: Significant progress has been made in understanding the steps involved
      in lung carcinogenesis and in the development of novel technologies for biomarker
      discovery. Over the last 3 years research into prospective lung cancer biomarkers
      has proliferated, especially in the areas of early detection and prognostication.
      The most active areas of research have been in promoter methylation, proteomics
      and genomics. Many investigators are adopting panels of serum biomarkers in an
      attempt to increase sensitivity. The development of targeted lung cancer therapy
      has engendered interest in markers to identify the optimal candidates for these
      therapies. SUMMARY: Much progress has been made in the last 3 years in the
      identification and validation of new biomarkers for the early diagnosis of lung
      cancer. The biomarkers require additional studies before they can be used
      clinically. Markers to identify lung cancer patients who may benefit from
      targeted therapy have been developed more rapidly and may be used now in some
      clinical situations.

PMID- 17534169
TI  - Positron emission tomography in nonsmall cell lung cancer.
AB  - PURPOSE OF REVIEW: [(8)F]2-Fluoro-2-deoxy-glucose positron emission tomography is
      an important functional imaging technique for the diagnosis, staging and follow
      up of patients with nonsmall cell lung cancer. We review recent developments with
      the emphasis on impact of positron emission tomography in early diagnosis,
      staging, restaging and prognosis of nonsmall cell lung cancer. RECENT FINDINGS:
      Data on the use and interpretation of positron emission tomography became
      available for small pulmonary nodules. We should abandon the 'magic' standardized
      uptake value threshold of 2.5 and rather make a visual assessment in this
      setting. The high negative predictive value of positron emission tomography in
      mediastinal staging was confirmed in a large prospective study. Tissue
      confirmation of all qualitative or quantitative suspicious mediastinal lymph
      nodes at positron emission tomography remains required. Minimally invasive
      techniques such as endobronchial ultrasound-guided transbronchial needle
      aspiration seem promising in this setting with sensitivities up to 90%. Recent
      data also point at integrated positron emission tomography/computed tomography as
      a tool for response assessment of mediastinal nodes and, more interestingly, of
      the primary tumor. Positron emission tomography has the potential to predict
      survival based on baseline positron emission tomography stage and standardized
      uptake value, visual [(18)F]2-fluoro-2-deoxy-glucose uptake at the time of
      suspected recurrence, and change in [(18)F]2-fluoro-2-deoxy-glucose uptake after
      neoadjuvant therapy. SUMMARY: Refinements in diagnosis and staging, as well as
      newer applications such as guidance of endoscopy and assessment of treatment, are
      described.

PMID- 17534170
TI  - Adenocarcinoma of the lung: current concepts in radiologic diagnosis and
      management.
AB  - PURPOSE OF REVIEW: Since the introduction especially of multidetector computed
      tomography scanners, detection of peripheral pulmonary nodules as small as 2-3 mm
      is now a frequent event even in individuals without a significant smoking
      history. This preponderance of small indeterminate nodules has necessitated
      reconsideration of the natural history of malignant lung tumors, in particular
      peripheral adenocarcinomas, as well as current clinical and radiologic guidelines
      to aid in the management of these lesions. RECENT FINDINGS: New information
      within the radiologic, pathologic and surgical literature is currently redefining
      nodule characterization. Most important has been the growing awareness of the
      prevalence of 'so-called' sub-solid pulmonary nodules, with important
      implications for revising our understanding of the natural history of these
      lesions as it impacts guidelines for nodule management. SUMMARY: Reassessment of
      our approach to small pulmonary nodules, while controversial, is now requisite as
      newer insights into the computed tomography appearance and natural history of
      small adenocarcinomas of the lung become apparent. Recognition of suspicious
      morphology and accurate measurements of volume doubling time, in particular,
      should aid in the management of these lesions.

PMID- 17534171
TI  - Video assisted thoracoscopic surgery and lobectomy, sublobar resection,
      radiofrequency ablation, and stereotactic radiosurgery: advances and
      controversies in the management of early stage non-small cell lung cancer.
AB  - PURPOSE OF REVIEW: Lung cancer is the most common cause of cancer related
      mortality in the United States. The fastest growing segment of the population has
      been the elderly, who frequently have other significant co-morbidities. In the
      medically inoperable, high-risk patient, new treatment options including
      minimally invasive surgery, computed tomography-guided ablative therapy and
      sterotactic radiosurgery are encouraging. The purpose of this article is to
      review some of these advances and emerging technologies in the management of
      early stage lung cancer, particularly in the high-risk patient. RECENT FINDINGS:
      In this article, we review the results of video-assisted thoracoscopic lobectomy,
      controversies surrounding lobectomy versus sublobar resection, and results of
      brachytherapy mesh as an adjunct to sublobar resection. Finally, we will review
      emerging technologies such as radiofrequency ablation and stereotactic
      radiosurgery in the treatment of lung neoplasm. SUMMARY: Lobectomy remains the
      standard for early stage lung cancer. In compromised patients, minimally invasive
      surgical approaches via thoracoscopy allow sublobar resection (wedge resection or
      segmentectomy) with or without adjunct brachytherapy mesh to offer results that
      approach that of lobectomy in some cases. Radiofrequency ablation and
      stereotactic radiosurgery are emerging technologies for the treatment of lung
      neoplasm, which are particularly applicable in high-risk patients who are not fit
      for even minimally invasive surgery. Prospective studies are underway in our
      center and others to further define the role of these new technologies in the
      treatment of lung neoplasm.

PMID- 17534172
TI  - Advances in bronchoscopic diagnosis of lung cancer.
AB  - PURPOSE OF REVIEW: In this chapter we will discuss two bronchoscopic advances in
      the diagnosis and staging of lung cancer. RECENT FINDINGS: Endobronchial
      ultrasound utilizes a flexible ultrasound probe fed through the working channel
      of a bronchoscope to image and biopsy lesions and lymph nodes beyond the wall of
      the bronchus. Electromagnetic navigation and guidance involves a specialized
      electromagnetic table with a computer program that maps the endobronchial tree
      and then helps navigate a bronchoscope to a particular lesion or lymph node.
      SUMMARY: We review a number of recent studies that utilize endobronchial
      ultrasound and electromagnetic navigation and guidance and analyze their
      performance characteristics for lung cancer diagnosis and staging as well the
      clinical applications of both technologies. Both are likely to play an increasing
      and integral role in the diagnosis and staging of lung cancer in the near future.
      Endobronchial ultrasound will likely have its greatest impact on mediastinal
      lymph node staging while electromagnetic registration may impact both staging and
      diagnosis of peripheral lesions.

PMID- 17534173
TI  - Tracheobronchial stenting and central airway replacement.
AB  - PURPOSE OF REVIEW: The present paper reviews the recent literature on the
      management of malignant large airway obstruction using tracheobronchial stenting
      and airway replacement by aortic allografts. RECENT FINDINGS: Airway stenting is
      a valuable adjunct to therapeutic bronchoscopy to relieve malignant airway
      obstruction. Over 80% of patients with obstructing lesions who were treated by
      airway stenting presented immediate symptom improvement in recent series.
      Stenting may also function as a bridge until further curative treatment can be
      used. Different stent models are available; their advantages and disadvantages
      depend on materials and constructions; clinical experience is larger with silicon
      based models than with metallic stents. An alternative strategy for the
      management of nonresectable primary tracheal tumors aiming to replace the central
      airway with an allogenic aortic allograft has been proposed. Experimental studies
      showed that an aortic allograft produced a respiratory conduit that shared
      fundamental elements of the trachea and newly formed cartilage rings were
      observed. SUMMARY: Airway stenting provides efficient palliation of symptoms in
      patients with malignant central airway obstruction. Evidence-based studies are
      needed to identify patients who may have the greatest benefit from stenting.
      Tracheal replacement with allogenic aortic allografts is a novel technique which
      brings hope to the management of extensive tracheal lesions.

PMID- 17534175
TI  - Diagnosis and treatment of bronchioloalveolar carcinoma.
AB  - PURPOSE OF REVIEW: Bronchioloalveolar carcinoma accounts for 5% of lung cancers,
      although histologically mixed bronchioloalveolar carcinoma and adenocarcinoma
      account for up to 20%. Bronchioloalveolar carcinoma histology is present in a
      majority of tumors found on lung-cancer screening by computed tomography. We
      review issues surrounding the diagnosis and treatment of bronchioloalveolar
      carcinoma, which often differs from other types of lung cancer. RECENT FINDINGS:
      A spectrum of disease from histologically pure bronchioloalveolar carcinoma to
      adenocarcinoma exists. The approach to treatment of diseases within this spectrum
      is still evolving. Evidence on the role of sub-lobar resection, resection of
      multifocal disease, and pulmonary transplantation is reviewed. We also discuss
      epidermal growth factor receptor tyrosine kinase inhibitors, and their role in
      patients with bronchioloalveolar carcinoma. SUMMARY: An understanding of recent
      developments in the diagnosis and treatment of patients with bronchioloalveolar
      carcinoma histology is important as early detection of lung cancer becomes more
      common. Ongoing clinical trials will provide important information on the role of
      limited resection. The use of epidermal growth factor receptor tyrosine kinase
      inhibitors should currently be limited to patients with advanced or recurrent
      disease who have failed cytotoxic chemotherapy. New targeted therapies are
      emerging for patients with bronchioloalveolar carcinoma histology.

PMID- 17534174
TI  - ERCC1 as a risk stratifier in platinum-based chemotherapy for nonsmall-cell lung
      cancer.
AB  - PURPOSE OF REVIEW: Cisplatin-based chemotherapy remains the treatment of choice
      in advanced nonsmall-cell lung cancer. The development of predictive biomarkers
      able to identify lung-cancer patients who are most likely to benefit from
      cisplatin-based chemotherapy would be a powerful tool. Many reports have explored
      the role of ERCC1 expression in the repair mechanism of cisplatin-induced DNA
      adducts in cancer cells. RECENT FINDINGS: Using immunohistochemistry in resected
      tumors, the International Adjuvant Lung Cancer Trial showed that high ERCC1
      protein expression was associated with improved survival in patients who did not
      receive chemotherapy. In contrast, the benefit of adjuvant cisplatin-based
      chemotherapy was more profound in patients with low ERCC1 expression. Other
      investigators studying mRNA expression in tumor biopsies from patients treated
      with cisplatin and gemcitabine showed that patients with low ERCC1 mRNA
      expression have a longer median survival compared to those with high expression.
      SUMMARY: High ERCC1 expression is predictive of resistance to platinum-based
      therapy. Thus, there is solid evidence to support ERCC1 as a useful marker of
      clinical resistance to platinum-based chemotherapy in the adjuvant setting of
      nonsmall-cell lung cancer. Meanwhile, optimization of methodology and
      standardization of technical procedures seem necessary before larger prospective
      studies can address the same question.

PMID- 17534176
TI  - Sequencing chemotherapy, radiotherapy and surgery in combined modality treatment
      of stage III nonsmall cell lung cancer.
AB  - PURPOSE OF REVIEW: Combined modality treatment is nowadays the standard of care
      in stage III nonsmall cell lung cancer, but the overall survival is still poor.
      Therefore, the challenge for clinicians is to optimize the combination of the
      treatment modalities. The review will focus on bimodality and trimodality
      approaches in stage III nonsmall cell lung cancer. Although the role of surgical
      resection in combined modality treatment is unclear, surgery will be discussed as
      a potential part of the treatment approach. RECENT FINDINGS: Concurrent
      chemoradiotherapy has proven to be more effective than chemotherapy followed by
      radiotherapy. Full-dose consolidation chemotherapy after concurrent
      chemoradiation showed an improvement of survival in some studies. Consolidation
      chemotherapy is, however, difficult to administer owing to its toxicity in these
      complex regimens. Both the Eastern Cooperative Oncology Group and the Radiation
      Therapy Oncology Group showed similar survival after surgery compared to
      sequential or concurrent chemoradiotherapy; however, pneumonectomies and residual
      malignant mediastinal disease after induction treatment had a negative impact on
      survival. SUMMARY: Concurrent chemoradiotherapy in combination with full-dose
      chemotherapy should be the standard of care for nonsmall cell lung cancer stage
      IIIA/B. Surgery is still experimental, but seems to be promising for certain
      subgroups of patients. More research has to be done in optimizing radiotherapy
      schedules and chemotherapy schemes in order to minimize toxicity. Novel
      therapeutics have to be introduced in the combined modality approach of stage III
      nonsmall cell lung cancer.

PMID- 17534177
TI  - Pleural effusions in the neonate.
AB  - PURPOSE OF REVIEW: This review highlights the pathophysiological mechanisms,
      incidence, clinical features, as well as the diagnosis and treatment of pleural
      effusions in the neonate. RECENT FINDINGS: Pleural effusions are rare except in
      hydropic neonates. Elevated pleural fluid/serum immunoglobulin G ratio may be a
      diagnostic marker for congenital chylothorax in utero. Chylothorax may be
      congenital or acquired. Hydrothoraces may appear at any time during the neonatal
      period and are related to infectious and noninfectious aetiologies. Haemothorax
      is defined as the presence of blood in the pleural space. Parenteral nutrition
      leakage may occur in a newborn with a venous central catheter leading to an
      effusion that looks like a chylothorax. The value of elevated pleural fluid N
      terminal pro-brain natriuretic peptide levels as a marker of congestive heart
      failure is not yet established in neonates. More recently, in cases of
      chylothorax that did not resolve with drainage and bowel rest, the use of
      somatostatin or its analogue octreotide has been described with success. If
      conservative management fails after 5 weeks, surgical intervention is indicated.
      SUMMARY: Clinicians must be aware of the wide range of disorders causing pleural
      effusions, the different types and clinical presentations, differential
      diagnosis, and how to treat each specific case.

PMID- 17534178
TI  - Therapeutic thoracentesis: the role of ultrasound and pleural manometry.
AB  - PURPOSE OF REVIEW: Therapeutic thoracentesis is one of the most commonly
      performed medical procedures. The availability of handheld ultrasound machines
      has greatly enhanced the evaluation and management of patients with pleural
      effusions, with advantages including the absence of radiation, ease of use,
      portability and real-time/dynamic imaging. Pleural manometry refers to the
      measurement of pleural pressure during thoracentesis. Though described more than
      122 years ago, most physicians do not measure pleural pressure, or even consider
      the role pleural pressures plays in the development of pleural effusions. This
      review summarizes the relevant data behind the use of ultrasound and manometry
      and explores their use during therapeutic thoracentesis RECENT FINDINGS: The use
      of ultrasound has been associated with a higher sensitivity for identifying
      pleural effusions, avoiding 'near misses' and a lower pneumothorax rate for
      thoracentesis. Pleural manometry can be used to distinguish patients with lung
      entrapment from those with trapped lung. Manometry is also able to predict the
      ability to pleurodesis patients with malignant effusions, and possibly minimize
      the risk of reexpansion pulmonary edema when large volumes of pleural fluid are
      removed. SUMMARY: The use of ultrasound and pleural manometry enhances the
      understanding of pleural disease and is associated with clinical benefit that
      will lead to improved patient care.

PMID- 17534179
TI  - Bacteriology of complicated parapneumonic effusions.
AB  - PURPOSE OF REVIEW: The bacteriology of complicated parapneumonic effusions has
      changed in recent decades, but the causative organisms often remain obscure in up
      to 40% of cases. Recently, new molecular methods have become available which
      might help clinical management and improve our understanding of this condition.
      In this review, we will consider the current bacteriological spectrum of pleural
      infection and look at some of the new molecular methods. RECENT FINDINGS:
      Hospital-acquired pleural infection exhibits a different bacteriology than
      pleural infection originating in the community. It carries a significantly higher
      mortality and requires different antibiotics at presentation. Streptococcal and
      anaerobic infections have low associated mortalities whereas staphylococcal,
      enterobacterial and mixed aerobic infections carry a worse prognosis. The yield
      of causative organisms can be significantly increased by the use of bacterial
      nucleic acid amplification and this may have a role in routine clinical practice
      in the near future. SUMMARY: The bacteriology of pleural infection has changed
      markedly in recent years. Mortality is highest with hospital-acquired pleural
      infection and infections caused by staphylococci, Enterobacteriacae and mixed
      aerobes. New molecular microbiological methods substantially increase bacterial
      yield in pleural fluid.

PMID- 17534180
TI  - Pleural effusions in superior vena cava syndrome: prevalence, characteristics,
      and proposed pathophysiology.
AB  - PURPOSE OF REVIEW: This review highlights recent data detailing the prevalence
      and characteristics of pleural effusions occurring in patients with superior vena
      cava syndrome. RECENT FINDINGS: Numerous case reports have described pleural
      effusions in conjunction with the superior vena cava syndrome. Recent data
      suggest that these effusions occur in 60% of superior vena cava syndrome cases.
      The effusions are small, usually occupying less than half the affected hemi
      thorax, and occur about equally on either side or bilaterally. Although
      previously thought to be largely transudates, a large case series found that 18%
      of the effusions were chylous, with the remainder being exudates. None of the
      effusions sampled in the series were transudates. Occluded lymphatic flow from
      increased hydrostatic pressure in the superior vena cava and left brachiocephalic
      vein probably contributes to the development of chylous pleural fluid. The
      pathophysiology of the exudative effusions, however, remains unknown. Many
      factors, including diuresis, small pulmonary emboli, and the underlying
      inflammatory or malignant condition all likely contribute. SUMMARY: Chylous or
      exudative pleural effusions occur in most patients with superior vena cava
      syndrome. The effusions are usually small and resolve upon correction of the
      underlying superior vena cava obstruction.

PMID- 17534181
TI  - Use of tunneled pleural catheters for outpatient treatment of malignant pleural
      effusions.
AB  - PURPOSE OF REVIEW: Malignant pleural effusion is a common complication in
      advanced malignancy that causes debilitating symptoms which result in impaired
      quality of life. The primary therapeutic goal in malignant pleural effusion
      management is effective palliation of the associated respiratory symptoms.
      Pleurodesis by chest tube or thoracoscopy is widely accepted as the gold standard
      treatment, although these treatments are not without problems. Tunneled pleural
      catheters represent a new safe and effective outpatient treatment option for
      these patients, with no reported mortality and minimal morbidity. RECENT
      FINDINGS: Chest tube insertion with talc slurry and thoracoscopy with talc
      insufflation are effective methods for achieving spontaneous pleurodesis,
      although associated with significant morbidity and mortality. A growing body of
      evidence is confirming that long-term palliation of malignant pleural effusion
      can be achieved by using tunneled pleural catheters in a large proportion of
      relatively unselected patients on an outpatient basis. SUMMARY: The optimal
      method for palliative management of malignant pleural effusion remains
      controversial. The high success rates, low complication rates and efficacy in
      patients with a wide range of performance status support the use of tunneled
      pleural catheters as a first-line treatment for symptomatic malignant pleural
      effusion.

PMID- 17534182
TI  - The risk of mesothelioma from exposure to chrysotile asbestos.
AB  - PURPOSE OF REVIEW: This review assesses the risk of developing diffuse malignant
      mesothelioma of the pleura from exposures to chrysotile fibers and contrasts it
      with the known risk of amphibole asbestos. RECENT FINDINGS: Although a rare
      cancer, the mortality rates of pleural mesothelioma continue to be significantly
      elevated because of past occupational exposures to airborne asbestos fibers. New
      analyses of occupational epidemiologic studies for highly exposed workers show a
      substantially lower potency and suggest an empiric threshold for chrysotile
      compared with amphibole asbestos. Important kinetic and pathological differences
      between chrysotile and amphiboles have been substantiated that support
      chrysotile's impotency in causing pleural mesothelioma. SUMMARY: Excess risk of
      pleural mesothelioma from past exposures to asbestos, as evidenced by a trend of
      high incidence rates during the last half century, appears to be the result of
      nonchrysotile asbestiform fibers. Although scientific efforts and legal arguments
      continue, the risk of pleural mesothelioma in human populations is probably
      negligible for exposures to airborne chrysotile asbestos that is not known to be
      contaminated by amphibole. This distinction for asbestos fiber types is pivotal
      for understanding hazards and characterizing risks of continued use of natural
      chrysotile asbestos today and also new nanofibers.

PMID- 17534183
TI  - Biomarkers for mesothelioma.
AB  - PURPOSE OF REVIEW: Mesothelioma is an incurable cancer and its global incidence
      continues to increase. There has been strong interest in the search for a
      biomarker that would be of value for the diagnosis, prognosis and disease
      monitoring of mesothelioma. Large series evaluating the use of novel candidate
      markers have recently been published. RECENT FINDINGS: To date, global gene
      profiling studies have failed to find a molecule that reliably captures all
      subtypes of mesothelioma, and differentiates it from benign pathologies and
      metastatic carcinomas. Soluble mesothelin-related peptide (SMRP), osteopontin and
      megakaryocyte potentiating factor have been assessed as markers. SMRP testing is
      clinically available and provides reasonable diagnostic sensitivity and
      specificity when applied to serum or pleural fluid. Elevated SMRP levels can
      occur in metastatic, especially ovarian and pancreatic, adenocarcinomas. False
      negatives are common with sarcomatoid mesothelioma. SMRP levels may reflect tumor
      load and disease progression. The role of SMRP in predicting mesothelioma
      development in subjects exposed to asbestos has raised interest. Osteopontin
      lacks specificity as a diagnostic marker for mesothelioma but may have value in
      disease monitoring. SUMMARY: The proposed markers have insufficient accuracy to
      replace cytohistology as the gold standard for diagnosis for mesothelioma.
      Elevated SMRP levels raise suspicion of mesothelioma although negative values do
      not exclude disease. Its role in disease monitoring in patients and in predicting
      disease development in at-risk individuals warrant further study.

PMID- 17534184
TI  - Biibliography. Current world literature. Neoplasms of the lung.

PMID- 17534185
TI  - Unicompartmental knee arthroplasty: technique through a mini-incision.
AB  - Unicompartmental knee arthroplasty is a logical procedure when the lesion is
      limited to one femorotibial compartment. The procedure can now be performed
      through a mini-incision to provide quicker recovery because the extensor
      mechanism disruption is minimized. We have found the length of the incision
      varies according to patient mass and muscle tone. Specific instrumentation
      limited to the replaced compartment and using either an intra- or extramedullary
      femoral technique provides femorotibial component alignment and allows slight
      undercorrection of the deformity. Radiographic assessment demonstrates precise
      implantation of the components is possible with a mini-incision, which is
      believed important for the long-term results of the arthroplasty. The functional
      evaluation of patients implanted with unicompartmental knee arthroplasty
      performed through a mini-incision suggests appropriate kinematics can be restored
      after the procedure, enhancing the importance of a functional anterior cruciate
      ligament. LEVEL OF EVIDENCE: Level V, therapeutic study. See the Guidelines for
      Authors for a complete description of levels of evidence.

PMID- 17534186
TI  - Does length of symptoms before diagnosis of sarcoma affect patient survival?
AB  - It generally is accepted that earlier diagnosis of sarcoma is associated with a
      better disease-free survival. Because the legal community is convinced this is
      true, a delay in cancer diagnosis is a frequent source of medical malpractice
      lawsuits. We asked whether symptom duration before diagnosis affected sarcoma
      outcome. We compiled prospective data from 624 consecutive patients with sarcoma
      treated from 1992 to 2003. The data included length of symptoms before diagnosis,
      tumor size and grade, presence of metastatic disease at diagnosis, anatomic
      location, disease-free survival, overall survival, and local recurrence. Length
      of symptoms did not predict presence of metastatic disease at diagnosis,
      survival, or disease-free survival. We found no correlation between the length of
      a patient's symptoms and the tumor size or anatomic site of disease (axial,
      proximal, and distal). Tumors were larger at diagnosis in axial and proximal
      locations than in more peripheral locations, despite no difference in length of
      symptoms before diagnosis. Patients with sarcoma with long-standing symptoms did
      not have a worse prognosis than those with a shorter length of symptoms before
      diagnosis in terms of disease-free survival, overall survival, and presence of
      metastatic disease at diagnosis.

PMID- 17534187
TI  - Novel TBX5 mutations in patients with Holt-Oram syndrome.
AB  - Holt-Oram syndrome (MIM #142900) is an autosomal-dominant disorder characterized
      by radial ray deformities of the upper limb associated with cardiac septation
      and/or conduction defects. The disorder is caused by mutations in the
      transcription factor TBX5. Several studies report a rather low detection rate
      (range, 22-35%) of TBX5 mutations in patients with a clinical suspicion of Holt
      Oram syndrome. The low detection rate is attributed to clinical misdiagnosis and
      genetic heterogeneity. However, a detection rate up to 74% has been reported when
      strict inclusion criteria for Holt-Oram syndrome are applied before genetic
      testing. We performed mutational analysis in a cohort of 27 unrelated patients
      referred with a clinical diagnosis of Holt-Oram syndrome. Seven TBX5 mutations
      were detected by direct sequencing. The detection rate of TBX5 mutations in this
      co hort of patients was 25.9% but increased to 54% when the strict phenotypical
      criteria were applied. No mutations were found in patients who did not meet these
      strict phenotypical criteria. Interestingly, we were unable to identify a TBX5
      mutation in six of 13 patients who did meet the strict criteria. This study
      confirms TBX5 genetic testing should be reserved for patients who fulfill the
      strict phenotypic criteria for Holt-Oram syndrome.

PMID- 17534188
TI  - Pedicle screw fixation of the cervical spine: guidance by computed tomography.
AB  - This is an anatomic, preclinical study using computed tomography and computerized
      simulation to describe the morphologic features and ideal screw insertion
      trajectories for cervical pedicles in the southern Chinese population. The
      morphologic features of the pedicle of vertebrae (C3-C7) from 20 human cadaver
      spines were evaluated with computed tomography and with manual measurements.
      There was no difference between the two data sets. The topography of the cervical
      pedicles was recreated graphically, calculating the safe range of the insertion
      angle with and without consideration of the pedicle screw diameter. Neglecting
      the diameter of the screw, the average safe ranges of the insertion angle at each
      cervical level (C3-C7) in the transverse plane were 18.7 degrees , 20.4 degrees ,
      22.4 degrees , 22.5 degrees , and 27.6 degrees , respectively, and in the
      sagittal plane 27.6 degrees , 30.3 degrees , 27.7 degrees , 29.0 degrees , and
      34.9 degrees , respectively. Including the diameter of the 3.0-mm screw, the safe
      ranges narrowed to 7.3 degrees , 8.6 degrees , 11.0 degrees , 13.1 degrees , and
      15.5 degrees in the transverse plane, and 16.4 degrees , 18.7 degrees , 16.4
      degrees , 18.3 degrees , and 23.1 degrees in the sagittal plane. We think
      computed tomography measurements can provide individual quantitative data for
      transpedicle screw fixation in the cervical spine.

PMID- 17534189
TI  - IL-1ra/IGF-1 gene therapy modulates repair of microfractured chondral defects.
AB  - Repair of cartilage defects involves sequential participation of specific
      hormones and growth factors with potential impairment by inflammatory cytokines.
      We explored an in vivo gene therapy treatment to supply adenoviral vectors
      carrying the genes of interleukin-1 receptor antagonist protein (IL-1ra) and
      insulinlike growth factor-1 (IGF-1), hoping to enhance repair of full-thickness
      equine chondral defects treated with microfracture. We asked whether our
      treatment could (1) increase proteoglycan and Type II collagen content in the
      repair tissue, (2) improve the macroscopic and histomorphometric aspect of the
      repair tissue, and (3) induce prolonged and increased IL-1ra and IGF-1 production
      in treated joints. Twelve horses had full-thickness chondral defects created in
      their carpus and stifle followed by microfracture. Joints were injected with
      either equine IL-1ra/IGF-1 adenoviral preparation or Gey's balanced salt
      solution. Sixteen weeks later, defect healing was evaluated macroscopically,
      histologically, histochemically, and biochemically. Production of IL-1ra and IGF
      1 was measured by enzyme-linked immunosorbent assay and radioimmunoassay. We
      found increased proteoglycan content in treated defects along with augmented Type
      II collagen associated with substantial transgene expression of IL-1ra during the
      first 3 weeks. These data suggest in vivo gene therapy can improve biologic
      processes associated with chondral defect repair.

PMID- 17534190
TI  - Fracture of the ABC ceramic liner: a report of three cases.
AB  - The fracture rate of third-generation ceramic liners is greatly reduced compared
      with first- and second-generation liners because of improvement in the design and
      manufacturing process. The ABC (alumina-bearing couple) ceramic liner is one such
      design, and fracture of this type of liner has not been reported. We report three
      cases of fracture of an ABC ceramic liner occurring within 3 years of
      implantation. The liner was broken into multiple pieces in two patients, whereas
      in one patient it was broken only in its periphery. These patients were treated
      with debridement and cementation of the metal-inlay polyethylene liner into the
      retained acetabular shell.

PMID- 17534191
TI  - Genetic association of complex traits: using idiopathic scoliosis as an example.
AB  - Although the exact etiology of adolescent idiopathic scoliosis is still
      undefined, genetic factors play an important role. Some patients have familial
      genetic disease that appears to have an autosomal dominant pattern. Linkage
      studies of these families revealed multiple potential genetic loci that may
      predispose individuals to the condition. Additional genetic analysis is required
      to identify the disease-predisposition genes of the loci found in the linkage
      studies. The initial localization of potential critical loci through large family
      based population studies now needs fine mapping by association studies using high
      density polymorphic markers (single nucleotide polymorphisms or SNPs). These
      markers are now available as a result of the Human Genome Project, International
      HapMap Project, and other genetic diversity projects. The application of this
      emerging data in a large association study of affected individuals and controls
      is integral for the identification of putative genes. With these complementary
      approaches, we will be able to progress with mutational analysis of hopefully a
      small set of candidate genes in the near future. In this commentary, we
      illustrate what is possible in the genomic era, and indicate what we should
      expect from genetic studies in adolescent idiopathic scoliosis, a complex trait
      disease.

PMID- 17534193
TI  - An unusual complication of radiofrequency ablation treatment of osteoid osteoma.

PMID- 17534194
TI  - Apoptotic gene analysis in idiopathic talipes equinovarus (clubfoot).
AB  - Idiopathic talipes equinovarus, also known as clubfoot, is a common birth defect
      occurring in one of 1000 live births. It is a complex disorder in which multiple
      genes and environmental factors may play an etiologic role. Several chromosomal
      deletion regions, including 2q31-33, are associated with talipes equinovarus and
      may harbor genes that contribute to the idiopathic talipes equinovarus phenotype.
      Previously, two STRs in the 2q31-33, GATA149B10 and D2S1371, showed linkage with
      association to idiopathic talipes equinovarus. Single nucleotide polymorphisms
      (SNPs) in three apoptotic genes (Casp8, Casp10, and CFLAR) near GATA149B10 were
      genotyped in idiopathic talipes equinovarus families. rs3731714 in Casp10 showed
      linkage with association, suggesting variation in the apoptotic gene pathway,
      which is important in limb morphogenesis, and may play a role in the development
      of idiopathic talipes equinovarus. We genotyped SNPs spanning seven apoptotic
      genes-Casp3, Casp8, Casp9, Casp10, Bid, Bcl-2 and Apaf1-in 210 simplex trios and
      139 multiplex families and tested for link-age and association to idiopathic
      talipes equinovarus. One SNP in each of the genes provided suggestive evidence of
      association with idiopathic talipes equinovarus. Several haplotypes constructed
      from these SNPs displayed altered transmission. These data suggest genetic
      variation in apoptotic genes may play a role in development of idiopathic talipes
      equinovarus.

PMID- 17534195
TI  - Higher risk of failure of methicillin-resistant Staphylococcus aureus prosthetic
      joint infections.
AB  - We determined the effect of methicillin resistance on the outcome of patients
      with Staphylococcus aureus prosthetic joint infections. From January 1995 to
      December 2004, 33% of 137 episodes of prosthetic joint infections were the result
      of S. aureus (in monomicrobial or polymicrobial cultures). Thirty-three (24%)
      episodes among 31 patients were the result of methicillin-susceptible S. aureus
      and 12 (9%) episodes among 12 patients were the result of methicillin-resistant
      S. aureus. Overall treatment failure rate was 38%. Patients with methicillin
      susceptible S. aureus or methicillin-resistant S. aureus prosthetic joint
      infections did not differ in age, gender, comorbidities, joint age, prior
      surgical procedures performed on the affected joint, number of postsurgical
      medical complications, or duration of intravenous antimicrobial therapy. Patients
      with methicillin-resistant S. aureus prosthetic joint infection had longer
      hospital durations (median, 15 versus 10 days). Methicillin-resistant S. aureus
      in periprosthetic tissue culture resulted in a higher risk of treatment failure
      (hazard ratio, 9.2; 95% confidence interval, 2.40-35.46) than methicillin
      susceptible S. aureus when controlling for joint location (total knee
      arthroplasty versus total hip arthroplasty [hazard ratio, 5.8; 95% confidence
      interval, 1.52-22.19]) and removal of hardware (hazard ratio, 0.24; 95%
      confidence interval, 0.077-0.75). Efforts should be made to prevent methicillin
      resistant S. aureus infections of joint arthroplasties and develop new treatment
      modalities.

PMID- 17534199
TI  - Anatomical vibrations that implantable microphones must overcome.
AB  - HYPOTHESIS: The goal of this study was to measure the tissue vibration amplitude
      that would be associated with an implantable microphone. BACKGROUND: Totally
      implantable hearing devices have been desired by the hard-of-hearing community
      for some time. However, an implanted microphone must pick up desired acoustic
      signals in the presence of undesired signals, including vibration. To design an
      effective microphone, the level of tissue vibrations originating from anatomical
      sources and the implanted transducer must be understood. METHODS: Using a laser
      Doppler vibrometer and an accelerometer, tissue vibrations were measured under
      the following conditions: (1) Normal control subjects during vocalization (n=4);
      (2) Vocalization and biological sounds measured on cranium and in soft tissue on
      normal subjects (n=6); (3) Transducer vibration measured on Otologics semi
      implantable hearing device wearer (n=1) and human cadavers (n=4 ears). RESULTS:
      Anatomical noise vibrations are 20 to 25 dB greater in soft tissue for
      frequencies less than 1,000 Hz than on the cranium, whereas vibrations due to
      implanted transducers are 20 to 25 dB greater on the cranium than in soft tissue
      inferior to the mastoid. Chewing vibrations are 10 to 15 dB greater than
      vocalization on the mastoid. Mastoid vibration levels measured in patients are
      equivalent to those in cadavers. Vibration levels do not vary significantly with
      respect to location on the cranium next to the pinna. CONCLUSION: The greatest
      anatomical vibrations that an implanted microphone must overcome are because of
      vocalization in the soft tissue inferior to the mastoid and chewing vibrations on
      the mastoid. A human cadaver is an appropriate model for transducer cranial
      vibration studies. If the implantable microphone is placed on the cranium near
      the pinna, it makes little difference with regard to actual location.

PMID- 17534202
TI  - Diagnosis and management of the patulous eustachian tube.
AB  - OBJECTIVE: The patulous eustachian tube (ET) seems to be caused by a longitudinal
      concave defect in the mucosal valve at the superior aspect of its anterolateral
      wall and causes troublesome autophony of one's own voice and breathing sounds.
      Patulous ET reconstruction was evaluated to analyze whether submucosal graft
      implantation to fill in the concavity within the patulous tubal valve may produce
      lasting relief of symptoms. STUDY DESIGN: Prospective trial. SETTING: Tertiary
      referral center, ambulatory surgery. PATIENTS: Fourteen ETs in 11 adults with 1
      or more years of confirmed continuous patulous ET symptoms refractory to medical
      care. INTERVENTION: Endoluminal patulous ET reconstruction was performed in 14
      separate cases using a combined endoscopic transnasal and transoral approach
      under general anesthesia. A submucosal flap was raised along the anterolateral
      wall of the tubal lumen up to the valve and mobilized superiorly off of the
      basisphenoid. The pocket was filled with autologous cartilage graft or Alloderm
      implant, restoring the normal convexity and competence to the mucosal lumen
      valve. MAIN OUTCOME MEASURE: Autophony symptoms were scored as 1) complete
      relief; 2) significant improvement, satisfied; 3)significant improvement,
      dissatisfied; 4) unchanged; or 5)worse. RESULTS: All 14 cases reported immediate
      complete relief of autophony. Results with an average follow-up of 15.8 months
      are as follows: 1 (7%) case had complete relief; 5 (36%) had significant
      improvement, satisfied; 7 (50%) had significant improvement, dissatisfied; and 1
      (7%) was unchanged. There were no complications. Correlation between patulous ET
      and other conditions was strongest with previous tubal dysfunction. Autophony of
      voice, but not breathing sounds, was also found to be experienced by 17 (94%) of
      18 patients with superior semicircular canal dehiscence syndrome and could be
      easily mistaken for patulous ET autophony. CONCLUSION: Patulous ET seems to be
      caused by a concave defect in the tubal valve's anterolateral wall. Submucosal
      graft implantation to restore the normal convexity to the valve wall seems to
      provide lasting relief of symptoms. Long-term study is needed. It is important to
      differentiate between the autophony of semicircular canal dehiscence syndrome and
      patulous ET.

PMID- 17534203
TI  - [Biomechanical evaluation of posterior instrumentation for lumbar burst fracture:
      comparison of two internal devices].
AB  - PURPOSE OF THE STUDY: Burst fractures generally occur due to trauma to the
      thoracolumbar spine. Surgery is indicated for unstable fractures. Posterior
      instrumentation with pedicular screws is generally proposed. In certain
      circumstances, hooks may be preferred due to excessive risk of insertion of the
      pedicular screw. The purpose of this study was to compare two posterior
      instrumentations, one using pedicular screws on either side of the fracture each
      protected by hoods and a second composed of the same pedicular screws inserted
      under the fracture hooks above. MATERIAL AND METHODS: Twelve spinal specimens
      from human cadavers composed of segments T10 to L2 were used. Range of flexion,
      extension, lateral inclination, and rotation were noted on T10 up to application
      of 7 Nm. Spinal segments were tested first intact, then in four configurations:
      1) instrumented without lesion, 2) lesion simulating burst fracture of L1 without
      section of the interspinous ligament, 3) and with section of the interspinous
      ligament, and 4) with L1 corporectomy. Finally a test to rupture was performed by
      applying a flexion moment up to fracture. RESULTS: Mean flexion-extension of the
      instrumented spine was limited compared with the intact spine for both
      instrumentation configurations and irrespective of the lesion. The same behavior
      was observed for lateral inclination with less pronounced motion with the first
      instrumentation. For rotation, the range of motion increased clearly with the
      second instrumentation and this with the first lesion while with the first
      instrumentation, rotation amplitude remained below that of the intact spine.
      There was however an increase in the vertical displacement during flexion
      extension for both instrumentations. For the rupture test, the mean flexion
      moment at rupture was 14.4 Nm (10.6-22 Nm) with no difference between the two
      instrumentations. DISCUSSION: This mode simulating burst fractures of the spine
      appears to be reproducible and more realistic than corporectomy. Attention should
      be taken concerning the limits of this type of study since fractures can occur
      for forces as small as 10.6 Nm. Thus we observed that pedicle screw
      configurations and also fractures produced mean ranges of motion greater than
      intact segments irrespective of the type of lesion simulated. However, the net
      increase in motion was observed during rotation movements when hooks were used,
      even when they were placed only below the fracture. Putting pressure on the hooks
      does not prevent them from slipping along the lamina. But neither of these two
      configurations controls the fracture gap. A vertebral reinforcement might be
      necessary.

PMID- 17534204
TI  - [Total hip arthroplasty in patients with chronic renal failure transplant or
      dialysis].
AB  - PURPOSE OF THE STUDY: Total hip arthroplasty (THA) is generally proposed for
      renal transplant patients with invalidating hip disease. For patients on chronic
      dialysis, the few published series report a higher rate of complications. These
      patients are considered more vulnerable. We report the results of a retrospective
      mid-term analysis of 28 renal failure patients (37 hips) with THA comparing renal
      transplant recipients with chronic dialysis patients. MATERIAL AND METHODS: THA
      was performed on 37 hips in 28 patients with renal failure between January 1993
      and 2004. Treatment for the renal disease was transplantation or chronic
      dialysis. Mean patient age at the time of the arthroplasty was 56 years. Nine
      patients had bilateral THA. At review, four patients had died and none were lost
      to follow-up. Mean time between transplantation and hip arthroplasty was 9.9
      years. Among the fourteen dialysis patients (21 hips), five had had a renal
      transplant. Mean time from onset of dialysis to arthroplasty was 12.3 years. At
      mean postoperative follow-up of six years (range 24 months to 12 years), 24
      patients were living. Thirty-five hips had no surgical history. Aseptic
      osteonecrosis was the dominant etiology (75% of operative indications in the
      graft group and 52% in the dialysis group). The preoperative Postel-Merle
      d'Aubigne score was 7.6 in the dialysis group and 10.3 in the graft group. Most
      of the cups were not cemented (n=31, 84%), as were most of the stems (n=29, 78%).
      All survivors were reviewed. The PMA score was determined. RESULTS: Early
      postoperative complications in the dialysis patients were: deep vein thrombosis
      (n=3), pulmonary embolism (n=4), operative site hematoma (n=2) and immediate
      septic complication with prompt revision and preservation of the implants (n=1).
      For the graft group, complications were: early dislocation (n=2), lung disease
      (n=3). Four patients, all in the dialysis group, died. At review, the mean PMA
      score was 14.2 in the dialysis patients and 15.7 in the graft patients. There
      were no radiological signs of loosening, nor of polyethylene wear, and no ectopic
      ossifications could be identified. There were no late infections. DISCUSSION: In
      renal transplant recipients, total hip arthroplasty is a reliable treatment for
      hip disease, providing good mid-term results and a morbidity close to that
      observed in the general population. Conversely, dialysis patients have a greater
      perioperative morbidity. Use of non-cemented implants is not associated with a
      higher rate of loosening than with cemented implants. It can be recalled that
      this type of surgery must be performed within the framework of careful
      pluridisciplinary patient management.

PMID- 17534205
TI  - [Prospective and comparative study of minimally invasive posterior approach
      versus standard posterior approach in total hip replacement].
AB  - PURPOSE OF THE STUDY: There have been few prospective studies comparing minimally
      invasive approaches for total hip replacement. We wanted to ascertain the
      contribution of the minimally invasive posterior approach in comparison with the
      standard posterolateral approach in terms of early outcome. MATERIALS AND
      METHODS: This was prospective comparative consecutive series of patients.
      Patients with major architectural problems or undergoing revision arthroplasty
      were excluded. One hundred ten patients (116 hips) were divided into two groups
      which were comparable for number of patients, gender, age, body mass index,
      indication for surgery, and preoperative function scores. The preoperative ASA
      score was lower in the minimally invasive group (p=0.04). The patients were in
      the lateral reclining position for the two approaches and classical
      instrumentation using the same implants (stems and cemented or non-cemented cups)
      were used. We noted operative time and blood loss (using the Brecher method based
      on the hematocrit at day 1 and 5 and the number of blood transfusions),
      postoperative pain, and implant position. Functional outcome was assessed with
      the modified Harris score and the WOMAC index (at 6 weeks and 3 and 6 months).
      Statview(R) was used to search for statistical significance considering p<0.05 as
      significant. RESULTS: Mean length of incision was 8.5 cm versus 15.1 cm. Mean
      blood loss was significantly less in the minimally invasive group (p=0.027) as
      was the level of postoperative pain as confirmed by the lesser consumption of
      morphine analgesics (p=0.006). Other operative variables as well as implant
      position were comparable. There were no major complications in the minimally
      invasive group. In the standard group, there was one case of common peroneal
      nerve palsy, two dislocations, and two fractures related to falls after
      prosthesis implantation. The WOMAC index was better after the minimally invasive
      approach at six weeks and at three months (p<0.05). The modified Harris score was
      better only at six weeks. Functional outcome and pain became comparable
      thereafter. DISCUSSION AND CONCLUSION: The minimally invasive posterior approach
      does not require an orthopedic table nor specific instrumentation. A minute
      procedure is required with ligature of the posteromedial circumflex artery of the
      thigh to improve exposure and limit intraoperative bleeding. It enables
      satisfactory reproducible implant positioning. Conversion to an open
      posterolateral approach is possible if needed. The minimally invasive posterior
      approach enables a reduction in intraoperative bleeding and in postoperative pain
      while allowing earlier more rapid rehabilitation. Early clinical outcome is
      better but beyond six weeks, the functional results are comparable for the two
      approaches. The minimally invasive posterior approach is a reliable reproducible
      approach with a progressive learning curve.

PMID- 17534206
TI  - [Computer-assisted surgery for acetabular cup positioning in total hip
      arthroplasty: comparative prospective randomized study].
AB  - PURPOSE OF THE STUDY: Actetabular component malpositioning during total hip
      arthroplasty (THA) increases the risk of dislocation, reduces the range of
      motion, and can be the cause of early wear and loosening. There have been
      numerous reports on the optimal orientation of the acebaular component in THA.
      Lewinnek et al recommended an abduction angle of 40+/-10 degrees and an
      anteversion of 15+/-10 degrees for cup alignment in THA. In order to prevent
      malpostioned hip implants and improve the reproducibility of implant alignment in
      THA, numerous computer-assisted orthopedic systems have been described, using
      computed tomography (CT)-base or imageless navigation. Among the imageless
      systems available, one is based on Bone Morphing technology initially described
      by Stindel for computer-assisted knee arthroplasty and adapted for THA. The
      purpose of this study was to compare computer-assisted acetabular component
      insertion versus free hand placement. MATERIAL AND METHODS: A controlled
      randomized matched prospective study was performed in two groups of 30 patients.
      The study was approved by the French Ethics Committee. In the first group, cup
      positioning was assisted by an imageless computer-assisted orthopedics system
      based on Bone Morphing(R) (CAOS+ group). In the control group, cup placement was
      free hand (CAOS- group). The same cementless cup was used in both groups. The
      same surgeon performed all procedures using an anterolateral approach. Cup
      anteversion and abduction angles were measured on 3D CT scan reconstructions
      obtained postoperatively for each patient by an independent observer using a
      special cup evaluation software. RESULTS: There were 16 males and 14 females in
      each group, mean age was 62 years (range 24-80) years, and mean body mass index
      was 25 in each group. Mean additional time of the CAOS procedure was 12 minutes
      (range 8-20). Intraoperative subjective agreement of the surgeon with the
      computer guidance system demonstrated a high correlation in 23 cases, a weak
      correlation in six cases and poor correlation in one case. There were no
      statistical differences between the CAOS+ and the CAOS- group regarding means of
      the abduction and anteversion angles, but a significant range of variance, the
      lowest variations being observed in the CAOS+ group. DISCUSSION: This study has
      shown the accuracy of cup positioning using a CT-free navigation system in a
      prospective randomized controlled protocol.

PMID- 17534207
TI  - [Hydroxyapatite-coated Esop modular femoral stem: three to ten year outcome in
      155 cases].
AB  - PURPOSE OF THE STUDY: Primary and secondary stability of the Esop prosthesis
      depends exclusively on cementless metaphyseal anchoring. This modular implant is
      composed of an hydroxyapatite-coated metaphysis on which a diaphyseal piece is
      added intraoperoperatively simply to act as a centering device. The purpose of
      this retrospective analysis of a consecutive series was to assess primary and
      secondary stability of the Esop implant by measuring axial migration over time.
      MATERIAL AND METHODS: Between 1995 and 2001, 172 primary total hip arthroplasties
      (THAs) were performed with the Esop femoral implant and the Atlas III acetabular
      implant. Six patients lost to follow-up and eleven patients who died were
      excluded from the analysis. The review thus concerned 155 THA in 128 patients (66
      women and 32 men), mean age 57 years (age range 28-77 years), 53% with an
      occupational activity at the time of surgery. Degenerative hip disease and
      aseptic osteonecrosis were present in 87% of patients. Imagika, a dedicated
      software, was used to measure axial migration and overall offset of the THA at
      four distinct times: on the immediate pre- and postoperative films, after
      introduction of weight-bearing, and at last follow-up (mean 61 months, range 35
      114 months). Survival and clinical and radiographic outcome were also assessed
      with the Postel-Merle-d'Aubigne (PMA) score. RESULTS: THA survival was 98%, all
      causes of failure included. The PMA score showed 97% excellent, very good or good
      outcome. Axial migration greater than 5 mm was demonstrated in ten hips (6.4%).
      Among these ten, seven exhibited migration during the first month than did not
      move further up to last follow-up. Comparison between the pre- and postoperative
      images revealed a 10 mm reduction in offset in 38% of hips, showing that the hip
      rotation center was medialized. DISCUSSION: Migration observed in ten implants
      corresponded to restablization at weight-bearing in seven. There was no
      correlation with the clinical outcome or poor radiological osteointegration.
      CONCLUSION: Primary and secondary stabilization of the Esop implant is
      satisfactory. In this series, the rotation center of the hip was globally
      medialized so that it would be useful to have available lateralized implants.

PMID- 17534208
TI  - [Acetabular revision for aseptic loosening in total hip arthroplasty using
      cementless cup and impacted morselized allograft].
AB  - PURPOSE OF THE STUDY: Impaction grafting can be used in cementless fixation with
      morsellized bone, bone graft, and hemispherical cup. The first goal of impaction
      grafting in revision of total hip arthroplasty is to transform segmental defects
      into cavitary defects and obtain a full compaction of the graft in order to
      restore the bone stock. The second goal is to achieve primary stability of the
      cup. The third goal is to restore the hip center of rotation with a cup
      anatomically located in the acetabulum. The aim of our study was to evaluate the
      results of a surgical technique with impacted morsellized bone graft and a
      cementless press-fit cup for the revision with defect type III according to the
      AAOS classification. MATERIAL AND METHODS: We performed a retrospective study
      including 34 hip reconstructions during revision of acetabular aseptic loosening
      with type III AAOS acetabular defects. All the revisions were performed in the
      same center by two senior surgeons. Mean age at surgery was 58 years. There were
      23 women and 11 men. All reconstructions were performed with a cementless cup and
      a morsellized impacted bone graft. The analysis of the acetabular defects was
      done preoperatively according to the AAOS classification. We analyzed
      postoperatively and at follow-up: position and stability of the acetabular cup,
      restoration of the hip center and graft integration. RESULTS: Mean follow-up was
      6.6 years (range 3-13 years). Complications included three dislocations, two
      trochaanteric nonunions. Two acetabular components were revised for septic
      loosening. According to the Kaplan-Meier survival curves, with endpoint criteria
      defined as acetabular cup removal, survival was 91.3% at 10 years (95CI: 86.3
      96.3). The preoperative Harris hip score was 53 points (range 26-86) and at last
      follow-up 94 (47-100). Concerning the subjective clinical outcome, 96% of
      patients were satisfied or very satisfied at last follow-up. 100% of cups were
      considered stable at follow-up and bone integration was good in 100%. The center
      of rotation was located in anatomic position mediolaterally in 66% and in the
      craniopodal plane in 44%. DISCUSSION: Restoration of bone stock is one of the
      main goals during hip reconstruction after aseptic loosening. Clinical experience
      in our series has shown the reliability of the impacted morsellized bone graft
      allowing relocation of the center of rotation and good cup stability. Biological
      fixation of the cup and graft integration seems good at mid-term follow-up. The
      cup that we used in our series combined the advantages of a press-fit cup and
      those of a reinforcement ring. The combination of this type of cup with
      morsellized bone graft seems to be a reliable solution for restoring bone stock,
      relocating the hip center, and stabilizing the cup in revision total hip
      arthroplasty with type III acetabular defect according to the AAOS
      classification.

PMID- 17534209
TI  - [Fixation of trochanteric or subtrochanteric fractures using dynamic external
      fixators].
AB  - We present a fixation system for trochanteric or subtrochjanteric fractures using
      a dynamic external fixator. The Citieffe/CH-N fixator was proposed for elderly
      patients with a significant operative risk (ASA III or IV). A long dynamic screw
      measuring 9 mm in diameter is inserted into the neck and the head of the femur on
      a guide wire through a tube protecting skin and muscles. This long screw is
      connected to the body of the fixator to enable impaction at the fracture level if
      compression is needed. The dynamic screw can be released to allow free gliding to
      achieve a dynamic fixation of the fracture. Distraction with the fixator can also
      be used for subtrochanteric unstable fractures to correct a varus deformity. This
      technique is a simple rapid solution with minimal operative risk. Complications
      are minimal and generally temporary, e.g. pin tract infections.

PMID- 17534210
TI  - [Syringomyelia and associated bone and joint diseases].
AB  - Syringomyelia can occur in patients presenting bone and joint diseases of various
      origins. When joint destruction of the shoulder or elbow produces little pain, a
      neurological cause might be involved. In this case, the disease history can be of
      utmost importance because an initial diagnosis of rheumatoid polyarthritis,
      polyosteoarthritis, or destructive joint disease can be misleading before the
      syringomyelic origin of the bone and joint disease becomes patent. We report two
      cases illustrating this association and the diagnostic pitfalls which can delay
      recognition of the syringomyelia. Better awareness of the prevalence of this
      condition should be helpful in establishing the diagnosis and in selecting
      patients who can benefit from neurosurgical treatment. The two cases presented
      here suggest that syringomyelia could be underdiagnosed in certain patients with
      an initially atypical presentation. A review of the current knowledge of
      syringomyelia suggests that arthroplasty is generally not advisable for destroyed
      dislocated syringomyelic joints.

PMID- 17534211
TI  - [Anaerobic sternocostoclavicular septic arthritis: a case report].
AB  - Septic arthirtis of the sternocostoclavicular joint is exceptional and usually
      occurs in immunodeficient subjects. The clinical presentation may be misleading,
      a rheumatoid disease often being suggested. We report a case of secondary joint
      infection caused by anaerobic bacteria and discuss the diagnostic problems
      involved as well as the disease course and the therapeutic options proposed in
      the literature. The diagnosis calls upon computed tomography and magnetic
      resonance imaging, leading to joint needle aspiration. Appropriate imaging
      enables an assessment of the anatomic damage and is useful for guiding surgical
      treatment under adapted antibiotic coverage.

PMID- 17534212
TI  - [Femoral metaphyso-diaphyseal chondroblastoma: a case report].
AB  - Chondroblastoma is a rare benign tumor of cartilage tissue accounting for less
      than 1% of all bone tumors. The epiphysis of long bones is the typical
      localization, often extending to the metaphysis. Metaphyseal, metaphysodiaphyseal
      or pure diaphyseal forms are exceptional. We report a case in a 15-year-old boy
      who presented a metaphyso-diaphyseal chondroblastoma of the distal portion of the
      left femur. The inaugural signs were pain and limited joint motion. We discuss
      the anatomic aspects and the clinical course of this rare tumor and present
      current knowledge of the histogenesis.

PMID- 17534213
TI  - [Metal on metal bearing surfaces in total hip arthroplasty: a survey of material
      incidents].
AB  - This study is dedicated to the problems met with metal-metal bearing prostheses.
      We have analysed the results of the reports sent to the AFSSAPS relating
      incidents described with this interface. Only 11 incidents were reported during
      the last 4 years by surgeons from different centers in France. At a mean follow
      up of 7 years, we collected 2614 total hip arthroplasties with metal-metal
      bearings and among them only 5 cases of unusual osteolysis and 10 cases of
      impingement. The bibliographic analysis did not show any severe specific
      complication due to the release of Cobalt or Chromium ions. The increased levels
      of Co an Cr in the patients' blood is now a well established notion (with more
      than 10 years follow up) and no special carcinogenetic effect has been correlated
      with the metal-metal bearings. Small diameter cemented cups can provide
      complications with high rates of acetabular loosening and metallosis; the same is
      true for some cementless cups also with loosening and a high revision rate. Among
      143 hip prosthesis with a cemented polyethylene cup, at a mean follow-up of 42
      months there were 22% of evolutive radiolucencies around the cups concerning all
      three De Lee and Charnley zones. Furthermore there was a statistically
      significant difference between small and large diameter cups (loosening of cups
      less than 46 mm in diameter). The same problem has been described for some
      cementless cups with loosening at the metal-bone interface due to a failure of
      osteointegration at the implant surface. However no failures were observed with
      an hydroxyapatite coating on the same cup. An other matter of concern is the
      skirted metal head: this design is responsible for a high rate of impingement and
      of prosthetic revision (2.3% among 642 THA). In these cases the increase of
      Cobalt serum levels was well correlated with the failure of the metal-metal
      interface. Large diameter heads decrease significantly the risks of dislocation.
      This is correlated with the increase in size. The release of ions in the blood
      was not affected by the large diameter compared to the regular size. So this
      overview confirms that if we respect some basic rules for the indications there
      are no specific complications related to the use of metal-metal bearings. In
      prospective studies the results of ceramic-ceramic and metal-metal bearings are
      similar but we must keep on observing prospectively the patients as for the
      release of Co and Cr.

PMID- 17534227
TI  - X-ray evaluation of symmetry development of human metatarsal bones in different
      periods of fetal life.
AB  - BACKGROUND: Symmetry and asymmetry have intrigued people for centuries. Most
      studies are based on adult specimens, and there are few asymmetry studies carried
      out on children and fetuses. The aim of this study was an x-ray evaluation of the
      asymmetry of human metatarsal bones in different periods of fetal life.
      MATERIAL/METHODS: The material consisted of 36 fetuses (18 male, 18 female). The
      fetuses were preserved in 10% formalin and the metatarsal bones were subsequently
      x-rayed in the A-P projection. Total area and length of the metatarsal bones were
      measured. The fetuses were divided into three groups according to fetal age
      calculated by measurement of the crown-rump length (CRL) and total length using
      the Scammon and Calkins methods. The results were put into tables which show
      which side of a sample bone pair is larger. RESULTS: Structural asymmetry in
      fetal metatarsal bones on the right and left side was found. In the younger
      group, the character of the asymmetry fluctuated. A clear one-sided domination in
      all metatarsal bones appeared only in the oldest group (over 26 gestational
      weeks). CONCLUSIONS: These result demonstrate that such asymmetry forms and
      matures during ontogenesis, similarly to other systems and organs.

PMID- 17534228
TI  - Urinary tract infections in Brescia, Italy: etiology of uropathogens and
      antimicrobial resistance of common uropathogens.
AB  - BACKGROUND: Urinary tract infections are associated with substantial morbidity
      and recurrent infections. Antibiotic therapy is generally initiated empirically
      because early treatment decreases the rate of morbidity resulting from UTI.
      Unfortunately, antibiotic resistance has become an increasingly pressing problem
      in many countries. In this study, the resistance patterns of urinary isolates to
      commonly used antimicrobials were determined in order to evaluate the options for
      empirical antibiotic therapy of UTI in out- and in- patients. MATERIAL/METHODS: A
      retrospective study was carried out on urine samples examined in this laboratory
      in 2002-2005. The isolates were divided into the following three groups: isolates
      from hospital inpatients, isolates from community outpatients, and isolates from
      catheterized patients. RESULTS: Escherichia coli was the most common etiologic
      agent isolated, followed by Enterococcus faecalis and Klebsiella pneumoniae. Over
      the four-year period, a decrease in the isolation of Pseudomonas aeruginosa and a
      parallel increase in Candida spp. in hospitalized patients were observed. Against
      Gram-positive isolates, enterococci in particular, ampicillin and glycopeptides
      demonstrated the best, most consistent activity. Among Escherichia coli isolates,
      nitrofurantoin, cephalosporins, and penicillin/betalactams were the best options
      for therapeutic treatment because of the presence of a rate of resistance to
      cotrimoxazole and fluoroquinolones of over 10%, while the most active drug
      against Pseudomonas aeruginosa was piperacillin/tazobactam. CONCLUSIONS: Region
      specific surveillance studies provide additional information about the type of
      pathogens causing UTIs and their antimicrobial susceptibility patterns.
      Therefore, these data can serve as a basis to develop national country-specific
      guidelines for the empirical treatment of UTIs.

PMID- 17534229
TI  - Immunomodulatory and apoptotic effects of Stachys obtusicrena on proliferative
      lymphocytes.
AB  - BACKGROUND: Several medicinal plants have shown anti-proliferative and apoptotic
      effects on human lymphocytes. In the present study the immunomodulatory
      properties of Stachys obtusicrena, a native plant to Iran, was examined and its
      possible effects on the induction of apoptosis were determined. MATERIAL/METHODS:
      The in vivo effect of the methanolic extract of S. obtusicrena on delayed type
      hypersensitivity (DTH) and antibody production was investigated in mice immunized
      with the antigen. The proliferation of human lymphocytes stimulated with mitogen
      in the presence of the extract was determined by [3H]-thymidine incorporation
      assay. Mitogen-treated lymphocytes were exposed to the extract and analyzed for
      induction of apoptosis using flow cytometry and gel electrophoresis. RESULTS:
      Data obtained from the DTH and antibody responses indicated a dose-related
      decrease in both parameters in the extract-treated mice compared with the
      untreated control group. In the in vitro study performed on the lymphocytes, the
      extract caused a dose-dependent decline in [3H]-thymidine uptake. The stimulation
      index of all cultures treated with different concentrations of the extract was
      less than 1. IL-2 levels in the culture supernatants of the activated lymphocytes
      showed a dose-related decrease as well. Results of flow cytometry indicated a
      dose-dependent accumulation of cells in the sub-G1 phase. The internucleosomal
      DNA fragmentation study showed typical DNA laddering in agarose gels.
      CONCLUSIONS: The present study showed inhibitory effects of S. obtusicrena on
      both cellular and humoral immune responses and suggests that this effect may in
      part be due to the induction of apoptosis in proliferative lymphocytes.

PMID- 17534230
TI  - Nosocomial bloodstream infections in a pediatric intensive care unit: 3-year
      survey.
AB  - BACKGROUND: Bloodstream infections (BSI) represent a major cause of hospital
      acquired infections in pediatric intensive care unit (PICU) patients. This study
      was designed to determine the prevalence, risk factors and outcomes of these
      infections in one local facility. MATERIAL/METHODS: All patients admitted to one
      PICU between January 1, 2000 - December 31, 2002 and subsequently developed a
      nosocomial bloodstream infection (NBSI) were consecutively recruited. The study
      was a retrospective study. Data retrieved from medical records included
      demographic information, extrinsic (invasive devices) and intrinsic risk factors,
      specific pathogens, therapeutic interventions and outcome. RESULTS: There were 95
      episodes of NBSIs in 59 patients (63/1711 PICU admissions, yielding an incidence
      of 56/1000). The crude mortality rate (CMR) in children with NBSIs was 52%,
      compared with 6% for all other children admitted to the PICU. A higher CMR was
      associated with hemato-oncology illness, prolonged length of hospitalization (>1
      month) mechanical ventilation, dialysis and severity of illness. Most of the
      patients (95%) had central intravascular devices, and 73% of the episodes were
      catheter-related infections. The most frequent pathogens were coagulase-negative
      staphylococci (24%), Klebsiella pneumonia (16%), Candida spp. (15%), Pseudomonas
      aeruginosa (7%) and Staphylococcus aureus (6%). Thirty-three percent of the
      Staphylococcus aureus were methicillin resistant (MRSA) and 30% of the Klebsiella
      pneumonia were extended - spectrum beta-lactamase - producing (ESBL) strains.
      CONCLUSIONS: The overall incidence of NBSIs was 56 episodes per 1000 admissions.
      The major risk factors were hemato-oncology illness, prolonged length of
      hospitalization, mechanical ventilation, dialysis and severity of illness.
      Children with NBSI had a poor outcome when compared with children without NBSI.

PMID- 17534231
TI  - A randomized control study on the effect of biphasic electrical stimulation in a
      warm room on skin blood flow and healing rates in chronic wounds of patients with
      and without diabetes.
AB  - BACKGROUND: Decrease in skin blood flow (BF) due to diabetes may be one reason
      why only 31% of neuropathic diabetic ulcers heal in 20-weeks. Recent evidence
      shows that skin blood flow may be increased if therapy is done in a warm room.
      The purpose of this investigation was to compare healing rates and skin blood
      flow of chronic stage III and IV wounds in people with diabetes (D) and those
      without diabetes (WD) using a warm room and electrical stimulation.
      MATERIAL/METHODS: Twenty subjects with chronic stage III and IV wounds were
      treated at an outpatient wound center. Ten were D, and ten were WD. Treatment
      consisted of biphasic electrical stimulation up to 20 ma for 30 minutes, 3 x week
      for 4 weeks in a 32 degrees C room. Skin blood flow was measured by a Laser
      Doppler Imager. RESULTS: BF increased not only during the stimulation (the
      increase in BF was greater for D at 87% than WD at 6%) at the outside of the
      wound but even at rest before stimulation started after the initial treatment
      creating a carryover effect. There was no increase in skin blood flow in the
      center of the wound. Healing rates over four weeks of up to 70% were seen in
      subjects with diabetes using biphasic current. CONCLUSIONS: Using stimulation in
      a warm room significantly increased healing and skin blood flow in these wounds.

PMID- 17534232
TI  - Loss of self-understanding: a behavior-oriented model of depression.
AB  - BACKGROUND: A new model of depression is proposed which is biological and
      explanatory on the behavioral level. It is hypothesized that a patient suffering
      from a depressive disorder loses the ability to produce one or more modes of
      behavior at a given time and simultaneously has the urge to produce one or more
      other modes of behavior constantly. The patient is also unable to interpret his
      behavioral disorder ("loss of self-understanding"). MATERIAL/METHODS: The authors
      developed the Salzburg Subjective Behavioral Analysis (SSBA) self-assessment
      questionnaire asking subjects to elaborate on changes in 35 modes of behavior and
      to interpret the behavioral disorder, if possible. The study was conducted using
      this questionnaire and the Hamilton Depression Scale on 30 inpatients with
      depressive disorders and this questionnaire on 30 healthy controls. RESULTS:
      Extreme positions in the SSBA were found in all 30 patients, compared with 2 in
      the 30 healthy controls. Significant correlation between the occurrence of
      extreme positions and the Hamilton scores was found (r=0.44, p=0.02) and
      correlation between the Hamilton scores and the inability of the patients to
      interpret the behavioral disorder was nearly significant (r=-0.35, p=0.06).
      CONCLUSIONS: The occurrence of extreme positions in the SSBA increased with
      depressive mood. In addition, the likelihood that subjects could explain their
      extreme positions in behavior decreased with increasing depression. The SSBA
      questionnaire assesses the self-evaluation of modes of behavior. As a diagnostic
      instrument, DSM-IV does not have criteria for modes of behavior. Thus, behavioral
      analysis should be considered in diagnosing depression.

PMID- 17534233
TI  - Effect of prolonged intra-aortic balloon pumping in patients with cardiogenic
      shock following acute myocardial infarction.
AB  - BACKGROUND: To evaluate the efficacy of prolonged intra-aortic balloon pumping
      (IABP) support in patients with cardiogenic shock following acute myocardial
      infarction (AMI). MATERIAL/METHODS: Thirty-nine patients with cardiogenic shock
      after AMI were treated with percutaneous coronary intervention which was
      supported by IABP. After 72 hours of IABP, the patients who attained the criteria
      of IABP withdrawal were randomly divided into two groups. The control group
      ceased IABP whereas the study group continued IABP for additional seven days.
      RESULTS: After IABP, mean arterial pressure, cardiac index, left ventricle
      ejection fraction and arterial oxygen saturation were significantly elevated in
      all patients whereas pulmonary capillary wedge pressure and heart rate were
      decreased. The improvement of cardiac index, left ventricular ejection fraction
      and pulmonary capillary wedge pressure in the study group was greater than the
      control group (P<0.05). After 12-month follow-up, the 6-min walking test and left
      ventricular ejection fraction in the study group were significantly higher than
      those of the control group (P<0.05). No significant differences were noted
      between the two groups in the incidence ventricular aneurysm and mortality rate.
      CONCLUSIONS: Prolonged use of IABP for up to 10 days offers additional long term
      benefit in left ventricular function and exercise tolerance.

PMID- 17534234
TI  - Benign paroxysmal positional vertigo and its management.
AB  - BACKGROUND: Benign paroxysmal positional vertigo (BPPV) is a common peripheral
      vestibular disorder encountered in primary care and specialist otolaryngology and
      neurology clinics. It is associated with a characteristic paroxysmal positional
      nystagmus, which can be elicited with specific diagnostic positional maneuvers.
      In recent years, specific therapeutic maneuvers have resulted in its effective
      treatment. In this paper the current knowledge of the pathogenesis, diagnosis,
      and treatment of BPPV as well as the authors' own clinical experience in treating
      such patients are presented. MATERIAL/METHODS: A retrospective review of the
      records of 204 patients with BPPV was performed. Epidemiological data and results
      from the audiological and neuro-otological work-up were recorded. All patients
      were treated with an appropriate repositioning maneuver, depending on the type of
      BPPV. RESULTS: Of the 204 patients, 163 had posterior canal involvement, 19 had
      horizontal canal involvement, and 6 had the anterior canal variant. Another 11
      patients had bilateral posterior canal involvement and 5 had disease of two
      canals. The canalith repositioning procedure was immediately successful in 165
      patients and in 23 more patients proved successful after its repetition in a
      second session, resulting in a total success rate of 92.1%. CONCLUSIONS: Most of
      the patients with BPPV responded very well to treatment. However, differential
      diagnosis of the type of BPPV was necessary to apply the appropriate canalith
      repositioning procedure. The canalith repositioning procedure is easy and safe to
      perform, is noninvasive, can be repeated if needed, and can provide rapid relief
      of vertigo.

PMID- 17534235
TI  - The frequency of ectopic thymic tissue in the necks of patients without any
      thymic disease.
AB  - BACKGROUND: Incidences of ectopic thymic tissue in the neck have been reported in
      various conditions. Despite their diversity, there are only a few studies
      focusing on patients without any thymic disease. The goal of this study was to
      detect the frequency of ectopic thymic tissue in the necks of adult patients
      without any thymic disease. MATERIAL/METHODS: Ninety patients with thyroid
      disorder who were candidate for thyroidectomy were selected. Five specimens were
      taken from each patient, including two biopsies before thyroidectomy from the
      right and left thyrothymic ligament just near the thyroid. The other specimens
      were taken after thyroidectomy: two from right and left carotid sheet at the base
      of the neck and the fifth from the adipose tissue just above the fourth tracheal
      cartilage. The specimens were stained with H&E and cytokeratin antibody to detect
      thymic tissue. RESULTS: Ectopic thymic tissue was found in four cases (4.45%),
      one by H&E and the others by immunohistochemical staining. CONCLUSIONS: In
      patients with myasthenia gravis, hyperplasia of thymic tissue occurs in their
      thymus gland and ectopic thymic tissue as well. As a result, the probability of
      finding ectopic thymic tissue in such a patient is higher than in patients
      without any thymic disease. Also, removing of this tissue can improve the outcome
      of patients.

PMID- 17534236
TI  - Cytogenetic results of recurrent spontaneous abortions in Turkey.
AB  - BACKGROUND: Recurrent spontaneous abortion is defined as at least three
      consecutive pregnancy losses, occurring in 10% of all pregnancies. In the
      etiology of recurrent spontaneous abortion, a wide variety of abnormalities, such
      as anatomic, endocrinologic, and genetic abnormalities, has been reported. The
      aim of this study was to compare karyotyping results of couples with recurrent
      spontaneous abortions. This may contribute to elucidating the genetic basis of
      this condition and warn physicians of the cytogenetic abnormalities in cases with
      recurrent spontaneous abortions. MATERIAL/METHODS: The cytogenetic results of
      patients with at least two abortions referred to Firat (Euphrates) University,
      College of Medicine, Department of Medical Biology and Genetics in the six-year
      period between 2000-2005 were reviewed retrospectively. RESULTS: Of a total of
      421 couples (842 patients), 23 men (2.73%) and 8 women (0.95%) had abnormal
      karyotypes. Balanced and unbalanced karyotypes and polymorphisms had rates of
      1.06%, 0.71%, and 1.9%, respectively, the total rate being 3.68%. CONCLUSIONS:
      These data show that cytogenetic evaluation is necessary for an accurate approach
      to elucidating the causes of recurrent spontaneous abortion, and physicians
      should also be careful of the diversity of chromosomal abnormalities that play
      important roles in the etiology of recurrent spontaneous abortion.

PMID- 17534237
TI  - Thyroid hormone resistance without mutations in thyroid hormone receptor beta.
AB  - BACKGROUND: Resistance to thyroid hormone (RTH) is a rare autosomal dominant
      disorder that leads to elevated free thyroid hormone levels in the presence of
      normal or increased serum thyroid-stimulating hormone (TSH) concentrations if it
      is generalized because both the pituitary and peripheral tissues are then
      partially resistant. In approximately 85% of patients with RTH, mutations in the
      thyroid hormone receptor beta (TR beta) gene can be identified. CASE REPORT: A 68
      year-old German man presented for surgical hernia repair. He was found to have
      elevated free T3 and T4 plasma concentrations in coexistence with goiter,
      unsuppressed TSH, arterial hypertension, and arthritis urica/gout. An
      electrocardiogram showed a normal sinus rhythm with 69 beats per minute. There
      were neither signs or symptoms of hyper- or hypothyroidism nor psychological
      abnormalities. Generalized RTH was suspected. CONCLUSIONS: Generalized RTH should
      be considered in patients presenting with elevated free thyroid hormone levels
      and normal or increased TSH concentrations, especially if these patients appear
      clinically euthyroid. Signs and symptoms of hyper- and hypothyroidism should be
      evaluated to assure that these patients are candidates for surgical procedures
      such as hernia repair. Subsequent mutation analysis of the TR beta gene should be
      conducted to help identify family members. In approximately 15% of patients,
      mutations in the TR beta gene cannot be identified and raise the possibility of
      mosaicism.

PMID- 17534238
TI  - An unusual presentation of an idiopathic omental pseudocyst: a case report and
      literature review.
AB  - BACKGROUND: Idiopathic omental pseudocysts occur very rarely in adults.
      Pseudocyst patients usually have a history of either trauma (e.g. seat belt
      injuries) or other related intra-abdominal pathology (e.g. pancreatitis,
      malignancy). They may result in a range of complications, from frequent abdominal
      pains with inconclusive diagnosis mimicking acute appendicitis, acute
      cholecystitis, or twisted ovarian cysts, to intestinal obstruction and
      peritonitis. CASE REPORT: A rare case of omental pseudocyst presenting as an
      acute intestinal obstruction in a 64-year-old woman without any previous history
      of significant abdominal pain, relevant medical problems, or trauma is reported.
      On plain abdominal x-ray, the cyst with dystrophic calcifications appeared as a
      dermoid cyst with multiple teeth. The optimal diagnostic methods, such as CT
      scanning and ultrasound imaging, which may show a well-circumscribed soft tissue
      mass are discussed. Uncomplicated and stable patients with established diagnosis
      can be treated conservatively. Surgical management includes resection of the cyst
      by either laparoscopy or laparotomy. CONCLUSIONS: Prognosis is good since omental
      cysts shows no documented tendency for malignant degeneration or recurrence.
      Optimal surgical management requires complete excision of these lesions.

PMID- 17534239
TI  - A therapeutic approach to perianal extramammary Paget's disease: topical
      imiquimod can be useful to prevent or defer surgery.
AB  - BACKGROUND: Extramammary Paget's disease (EMPD) is a rare skin disease which can
      be limited to the epidermis and can sometimes also be associated with underlying
      carcinomas. At clinical examination, lesions are well-defined eczematous areas
      and have been described typically in the anogenital region. Surgery is the
      cornerstone treatment. CASE REPORT: In this report the case of a 66-year-old
      patient presenting with a long-lasting EMPD of perianal region without deep
      gastrointestinal neoplasia is described. Because of the extension of the lesion,
      surgery should have led to abdominoperineal amputation, but the patient rejected
      this option. Three months of daily application of topical imiquimod was
      prescribed as an alternative treatment. Biopsy-confirmed complete regression
      could be observed thereafter, and no recurrence has been noted during a 12-month
      follow-up. CONCLUSIONS: This successful treatment of a perianal-located EMPD by
      topical imiquimod warrants further investigations.

PMID- 17534240
TI  - Detrimental factors during positive-pressure ventilation: pressure, flow, and/or
      volume?

PMID- 17534242
TI  - RAPD typing of methicillin-resistant Staphylococcus aureus: a 7-year experience
      in a Polish hospital.
AB  - BACKGROUND: Methicillin-resistant strains of Staphylococcus aureus (MRSA) are
      important etiological factors responsible for healthcare-associated infections.
      The aim of this study was to evaluate the epidemic and to discriminate all of the
      involved strains isolated at the Provincial Hospital in Gdansk and, on this
      basis, perform an epidemiological investigation using the random amplification of
      polymorphic DNA PCR (RAPD) with the primer AP-7. MATERIAL/METHODS: Two hundred
      and thirty-four isolates of Staphylococcus aureus were typed to evaluate a seven
      year epidemic of MRSA at the hospital. All isolates were recovered from infection
      and carriage sites of patients. Numerous strains were isolated from patients
      suffering from generalized infections, bacteremia, and endoprosthesis-related
      infections. RESULTS: Using the RAPD PCR method, the collection of 234 MRSA
      strains was divided into 10 groups, one of which was the most common (81%). No
      correlation between the S. aureus clones determined in this way and hospital
      department or the type of infection was found. CONCLUSIONS: It was confirmed that
      MRSA infections may be easily spread throughout a hospital and that the
      introduction of a surveillance program implemented with control procedures is
      sufficient to restrict serious problems such as an MRSA epidemic.

PMID- 17534243
TI  - Update on the antibacterial resistance crisis.
AB  - This nation--and in fact the world--is currently facing a crisis in the form of a
      growing antibacterial drug resistance. In the 60 or so years since the discovery
      of penicillin, physicians and pharmaceutical companies have been constantly
      challenged to stay a step ahead of the bacteria that constantly adapt to the
      drugs used to control them. These magic bullets were at one time expected to
      eliminate the concern over infectious disease and have been relied upon heavily.
      But their effectiveness has been steadily waning in recent years as, more and
      more, strains of bacteria emerge that are resistant to multiple drugs and, in
      some cases, have become nearly "panresistant." Nosocomial infections with these
      resistant strains were once confined to hospitals but new community-acquired
      infections are an ominous portent. Meanwhile, perhaps equally as distressing,
      many pharmaceutical companies are discontinuing efforts to develop new
      antimicrobial drugs for a variety of reasons and few new agents are currently in
      the pipeline. The selective pressure triggering these bacterial mutations are
      complex, but they can be shared by healthcare workers, hospitals, long-term care
      facilities, the agriculture industry, and even healthcare consumers themselves.
      In this paper, these topics are discussed, in turn, and the paper concludes with
      an apologia for change that can and should be equally shared by these
      stakeholders.

PMID- 17534244
TI  - Growth related oncogene-alpha (GRO-alpha): roles in atherosclerosis, angiogenesis
      and other inflammatory conditions.
AB  - Growth related oncogene-alpha (GRO-alpha) is a member of the CXC chemokine family
      with an internal glutamate-leucine-arginine (ELR) motif. It was initially
      isolated and characterized by its growth stimulatory activity on malignant
      melanoma cells. Recently, many new functions and properties of GRO-alpha have
      been discovered and associated with atherosclerosis, angiogenesis and many
      inflammatory conditions. Purpose of this review is to overview current advances
      of multiple functions of GRO-alpha and its associated molecular mechanisms and
      clinical implications. We hope to further evaluate this molecule in the
      pathogenesis of atherosclerosis as well as angiogenesis to promote a background
      for therapeutic interventions.

PMID- 17534245
TI  - Nicotine, alcohol and cocaine coupling to reward processes via endogenous
      morphine signaling: the dopamine-morphine hypothesis.
AB  - Pleasure is described as a state or feeling of happiness and satisfaction
      resulting from an experience that one enjoys. We examine the neurobiological
      factors underlying reward processes and pleasure phenomena. With regard to
      possible negative effects of pleasure, we focus on addiction and motivational
      toxicity. Pleasure can serve cognition, productivity and health, but
      simultaneously promotes addiction and other negative behaviors. It is a complex
      neurobiological phenomenon, relying on reward circuitry or limbic activity. These
      processes involve dopaminergic signaling. Moreover, nicotine, cocaine and alcohol
      appear to exert their pleasure providing action via endogenous morphinergic
      mechanisms. Natural rewarding activities are necessary for survival and
      appetitive motivation, usually governing beneficial biological behaviors like
      eating, sex and reproduction. Social contacts can further facilitate the positive
      effects exerted by pleasurable experiences. However, artificial stimulants can be
      detrimental, since flexibility and normal control of behavior are deteriorated.
      Additionally, addictive drugs are capable of directly acting on reward pathways,
      now, in part, via endogenous morphine processes.

PMID- 17534246
TI  - Direct coronary stenting versus stenting with balloon pre-dilation: incidence of
      enzyme release and follow-up results of a multicentre, prospective, randomized
      study. The CK and Troponin I Estimation in direct STenting (CK TEST) trial.
AB  - AIM: The aim of this study was to assess the safety of direct coronary stenting,
      its influence on costs, duration of the procedure, radiation exposure, clinical
      outcome and the incidence of periprocedural myocardial damage as assessed by
      enzyme release determination. METHODS: We randomized 103 patients (109 lesions)
      to direct stent implant or stent implant following balloon predilatation.
      Patients with heavily calcified lesions, bifurcations, total occlusions, left
      main lesions and very tortuous vessels were excluded. Three samples of blood were
      drawn; before, 12 and 24 h after the procedure and total CK, CK MB mass and
      troponin I determination was carried out in a single centralized laboratory.
      RESULTS: Direct stenting was successful in 62/62 lesions (100%). No single loss
      or embolization of the stent occurred. All stents in the group with predilatation
      were effectively deployed. The immediate post procedure angiographic results were
      similar with both techniques. Contrast media consumption and procedural time were
      significantly lower in direct stenting (150+/-82 cc and 30+/-13 min) than in pre
      dilated stenting (184+/-85 cc and 36+/-14 min) (P=0.04 and P=0.036 respectively)
      while fluoroscopy time was similar (9.1+/-12 vs 9.19+/-15 min, P=0.97). The
      incidence of enzyme release was similar in the groups with only three non Q MI
      all in the pre-dilated group (P=0.149). Any elevation of CK MB and troponin I
      occurred in 7% of direct stent vs 12% of pre-dilated group (P=0.66), isolated
      troponin I elevation in 21% of both groups. Major adverse cardiac events during
      hospitalization were 0 in direct and 3 in pre-dilated stenting (P=0.66), but
      there were no significant differences at follow-up at 1, 6 and 12 months between
      the 2 groups (target lesion revascularization at 12 months 11 vs 14% in the 2
      groups respectively). CONCLUSION: Direct stenting is as safe as pre-dilated
      stenting in selected coronary lesions. Acute results and myocardial damage as
      assessed by enzyme release determination are similar, but procedural costs (as
      measured by resource consumption) and duration of the procedure are lower in
      direct stenting. Overall success rate and mid-term clinical outcome are similar
      with both techniques.

PMID- 17534247
TI  - Imaging the whole body atherosclerosis: high resolution magnetic resonance
      angiography using blood-pool agent. Initial clinical experience.
AB  - AIM: Recently whole-body 3D MR angiography (MRA) with blood-pool contrast agent
      has become available. The purpose of this study was to introduce and evaluate
      this technique to demonstrate arterial steno-occlusive involvement in systemic
      atherosclerosis and to compare blood-pool enhanced MRA results with those of CT
      angiography (CTA) as reference modality. METHODS: Twenty patients with clinically
      and US documented carotid occlusive disease underwent whole-body MRA on a 1.5 T
      scanner and CTA on a 64-MDCT unit. Ten milliliters of a blood-pool agent (MS-235
      Gadofosveset Trisodium, VASOVIST, Schering, Berlin, Germany) were administered
      intravenously and four 3-D MRA stations were acquired successively through
      automatic table moving. Images were reviewed by two observers. Overall image
      quality of each arterial segment was assessed and rated for both MRA and CTA
      examinations; MRA sensitivity, MRA specificity interobserver and intermodality
      agreement were calculated. RESULTS: Whole-body MRA with blood-pool contrast agent
      was well tolerated by all patients. It yielded a detailed display of the arterial
      system with a short examination time. In 14 out of 20 patients there was
      extensive involvement of the arterial bed by steno-occlusive atherosclerotic
      disease; for the identification and characterization of vessel damage in the
      various vascular districts MRA sensitivity was 92-100%, MRA specificity was 95
      100%; in 2 cases MRA underestimated the degree of peripheral vessel stenosis.
      Interobserver agreement calculated with K value was 0.63, intermodality agreement
      with CTA was 93% (P<0.01). CONCLUSION: The whole-body MRA technique is a valuable
      tool for comprehensive evaluation of arterial steno-occlusive involvement in
      systemic arterial atherosclerosis; there is a good agreement between blood-pool
      enhanced MRA results and CTA, used as modality of reference.

PMID- 17534248
TI  - Transradial access in a cath lab with moderate procedural volume: a single
      operator's experience.
AB  - AIM: The transradial access (TRA) for cardiovascular interventions has become
      increasingly popular and was shown to be effective in many clinical settings,
      including acute coronary syndromes. Despite offering many advantages, such as a
      striking reduction in access site complications, the penetration of TRA in
      routine practice is still low. One reason for this could be that many studies
      about TRA were performed in high-volume centers by expert operators, making their
      results not fully applicable to the real world. In order to assess the efficacy
      of TRA, we retrospectively reviewed the caseload of a single operator working in
      a community hospital with moderate procedural volume. METHODS: We considered 873
      consecutive procedures, of which 406 percutaneous coronary interventions (PCI),
      performed by a single operator (S.R.) who had previously completed the learning
      curve in TRA at a high volume center. RESULTS: TRA was selected in 48.3% of
      patients, transfemoral approach (TFA) in 50.9% and transbrachial approach in
      0.8%. TFA was used more frequently in PCI (62.5% vs 37.5%; P<0.001), largely
      because it was the access of choice in primary PCI. The overall procedural
      success rate was 94% in TRA and 98% in TFA (P=0.035); access failure was more
      frequent in TRA (5.9% vs 1.1%; P<0.001), whereas an increased rate of access
      related vascular complications was observed in TFA as compared to TRA (1.1% vs
      0%; P=0.029). CONCLUSION: After an adequate training period, the overall
      performance of TRA is good even in moderate-volume hospitals. Despite reducing
      access site complications, TRA is limited by a slightly higher rate of procedural
      failure as compared to TFA.

PMID- 17534249
TI  - Inefficiency of renin-angiotensin inhibitors in preventing atrial fibrillation in
      patients with a normal heart.
AB  - AIM: Recent scientific evidence has emphasized the possible role of inhibitors of
      the renin-angiotensin system in preventing arrhythmic relapses in patients with
      paroxysmal or persistent atrial fibrillation and co-existing left ventricular
      hypertrophy or left ventricular dysfunction. METHODS: In order to verify the
      effects of these drugs on patients with a normal heart, we collected a series of
      187 patients admitted to our division of cardiology for paroxysmal or persistent
      atrial fibrillation. All patients underwent cardioversion (with antiarrhythmic
      drugs and/or by electrical cardioversion) and were discharged in sinus rhythm.
      Episodes of recurrent arrhythmia were recorded during a mean follow-up period was
      2 years. Patients were subdivided into 2 groups according to therapy: group 1
      comprised patients receiving renin-angiotensin system inhibitors, group 2
      comprised those not receiving therapy with these agents. All 91 patients in group
      1 and 76 of those in group 2 had hypertension. Among the 91 patients in the group
      1, 55 were treated with angiotensin-converting enzyme (ACE) inhibitors and 36
      with angiotensin receptor blockers. There were no statistically significant
      differences in cardiovascular risk factors or antiarrhythmic drug use between the
      2 groups. RESULTS: In group 1, 83% of patients experienced <2 recurrences of
      atrial fibrillation during the follow-up period, while 17% had >2 episodes. In
      group 2, 86% of patients experienced <2 relapses during the follow-up period,
      while the remaining 14% had >2 relapses. There was no statistically significant
      difference between the 2 groups (P=0.85). A subgroup analysis showed that
      treatment with angiotensin receptor blockers, beta-blockers, diuretics, and
      calcium-channel blockers brought no advantage in sinus rhythm maintenance.
      CONCLUSION: In our sample of hypertensive patients with a healthy heart,
      treatment with ACE inhibitors showed no statistically significant advantage in
      the prevention of atrial fibrillation relapses.

PMID- 17534250
TI  - Is dobutamine stress echocardiography predictive of middle and late term outcomes
      in mitral stenosis patients?
AB  - AIM: In mitral stenosis (MS) patients with a poor symptom-echocardiography
      correlation, dobutamine stress echocardiography (DSE) still does not have a
      confirmed utility and predictive value. Our aim is to evaluate usefulness of DSE
      in assessing 2 and 5 years clinical outcomes. METHODS: Forty-four consecutive
      patients with known MS were submitted, between April 1998 and July 1999, to basal
      and DSE. Patients were divided in 2 groups: group A if during DSE was reached a
      mean mitral gradient (MG) = or > 15 mmHg and/or a pulmonary arterial pressure
      (PAP) = or > 60 mmHg, and group B if MG and/or PAP were respectively lower than
      15 and 60 mmHg. Endpoints considered were death, hospitalization for acute
      pulmonary edema, complications associated with mitral valve disease and mitral
      valve interventions (percutaneous or surgical). Mean follow-up was 73.6+/-16.6
      months. RESULTS: Mean age was 55.2+/-10.5 years; 83.7% were women; NYHA class was
      I-II-III respectively in 18.6%, 58.1% and 23.3% of the patients; mean mitral
      valve area was 1.39+/-0.26 cm2; mean MG 8.05+/-2.54 mmHg; PAP 39.3+/-7.9 mmHg.
      Twenty-five patients met criteria for group A and 18 for group B. The event-free
      interval (27.9+/-32.1 months in group A vs 53.5+/-25.8 months in group B;
      P=0.008) and the 2 years event-free survival (40% for group A vs 88.9% for group
      B; P=0.002) showed significantly different patterns between the 2 groups. The 5
      years survival analysis did not reach significance. CONCLUSION: DSE seems to
      detect MS patients that will have rapid evolution of their valvular disease
      within 24 months.

PMID- 17534251
TI  - Autonomic nervous system in the genesis of arrhythmias in chronic heart failure:
      implication for risk stratification.
AB  - Sudden cardiac death (SCD) is one of a major cause of morbidity and mortality in
      patients with chronic heart failure (CHF). There is a circadian variation of the
      frequency of SCD. Beta-blocker therapy significantly reduces the incidence of
      SCD. These clinical observations suggest a close association between ventricular
      arrhythmia and sympathetic activity. The identification of patients at risk is a
      major clinical problem not only for the unpredictability of the event, but also
      for the continuous growth of patients'number. The implantable cardioverter
      defibrillator (ICD) is highly effective at terminating life threatening
      ventricular tachyarrhythmia At present, 1-2% of the population has heart failure
      and numbers continue to increase, but the ICD remains expensive. The challenge
      lies in identifying patients with heart failure who are at significant risk of
      arrhythmia and who would benefit from an ICD in addition to other anti-arrhythmic
      strategies. Our power of identifying heart failure patients at risk for
      arrhythmic death is far from being satisfactory. Heart rate variability and
      baroreflex sensitivity analysis has been largely utilized to obtain information
      on autonomic modulation of sinus node as well as to identify patients at risk. It
      is possible that the combination of results of multiple noninvasive tests such as
      reduction in ejection fraction and positivity for T wave alternans may not only
      provide general prognostic information but also facilitate the appropriate
      identification of patients at risk who may benefit from antiarrhythmic therapy.

PMID- 17534252
TI  - Role of echocardiography in the assessment of mechanical dyssynchrony.
AB  - The aim of this paper is to summarize the current scientific evidence regarding
      the prognostic implications of mechanical asynchrony, the benefits of identifying
      mechanical asynchrony prior to cardiac resynchronization therapy by means of
      echocardiography to predict response to cardiac resynchronization therapy and the
      different described parameters for dyssynchrony evaluation and measurement.

PMID- 17534253
TI  - Post automatic implantable cardioverter defibrillator implant therapies: drugs
      and ablative techniques.
AB  - The aim of this article is to report the evidences about the use of drugs and
      ablation after implantation of a cardioverter defibrillator. Drugs can be
      utilized to prevent appropriate and inappropriate shocks, can influence
      positively or negatively defibrillation threshold, can be useful for the
      treatment of electrical storm. Ablation can be performed for direct cure of
      coexisting atrial and ventricular tachyarrhythmias or for AV node modulation. In
      particular, previous data demonstrate that rescue ventricular tachycardia
      ablation of drug-refractory electrical storm is possible by a substrate
      orientated ablation approach even in patients with complex chronic infarction and
      various ventricular tachycardias. At the end of this article it is described how
      remote monitoring, a new very promising technical improvement, can be utilized
      for deciding, almost in real time, the use of both these therapies or for
      controlling their efficacy.

PMID- 17534254
TI  - Complications associated with catheter ablation of atrial fibrillation.
AB  - Atrial fibrillation is the most common clinical arrhythmia, affecting millions of
      people worldwide and utilizing billions of dollars annually in heath care costs
      associated with the disease. Catheter based ablation, centering around the
      electrical isolation of the pulmonary veins, has emerged as a viable treatment
      option for patients with symptomatic paroxysmal or persistent atrial
      fibrillation. Because of the complex nature of the procedure, there are a number
      of potential complications which can occur which are related to problems with
      vascular access, mechanical complications resulting from catheter manipulation
      within the heart, cardioembolic complications, and complications arising from the
      effects of radiofrequency ablations in the left atrium. The most frequent
      complications arise from pseudoaneurysms, arterio-venous fistulas, hematomas,
      neurologic events (stroke and transient ischemic attacks), and pericardial
      effusion/tamponade. An evolving understanding of the risks of the procedure have
      helped to minimize complications by changing ablation strategies to avoid lesion
      delivery within the veins, emphasizing careful attention during the procedure to
      anticoagulation, utilizing intracardiac ultrasound and electroanatomic mapping
      systems for better visualization of intracardiac structures, and recognizing
      complications promptly during and after the procedure. Hopefully, improved
      techniques in the future will help to further improve the safety of catheter
      ablation of atrial fibrillation to allow for continued growth of this procedure.

PMID- 17534255
TI  - Surgical treatment of atrial fibrillation.
AB  - Atrial fibrillation is a very common arrhythmia that carries a considerable risk
      of thromboembolic complications. Surgical treatment is an effective way to
      convert atrial fibrillation into sinus rhythm and significantly prevents
      thromboembolism postoperatively. In this review we describe recent advancements
      in the surgical options and detail our strategy for the surgical treatment of
      atrial fibrillation.

PMID- 17534256
TI  - Risk stratification for sudden death in heart failure.
AB  - Clinical trials provide evidence that an empiric approach of implantable
      cardioverter-defibrillator (ICD) implantation in heart failure patients (ejection
      fraction =/< 35%) with mild to moderate symptoms reduces mortality rate as
      compared to the best available medical therapy. However, ejection fraction alone
      is unable to predict death by progressive pump failure or sudden arrhythmic
      death, and consequently over half of all patients will not require device therapy
      over long-term follow-up. Thus, the approach of empiric ICD implantation results
      in excessive cost in the absence of more specific risk stratification for sudden
      death. This review summarizes the current noninvasive risk stratifying strategies
      available in predicting susceptibility to sudden arrhythmic death in heart
      failure populations.

PMID- 17534257
TI  - Novel method of biventricular pacemaker optimization by radial artery tonometer.
      A case report.
AB  - Echocardiographic guided pacemaker optimization leads to significant improvement
      in cardiac function among nonresponders to cardiac resynchronization treatment
      (CRT). Simpler, noninvasive determination of cardiac function during
      biventricular pacemaker programming may simplify this procedure. In this report
      we describe a 73 year old male patient who presented with recent onset NYHA class
      III symptoms 7 months post-CRT for ischemic cardiomyopathy. During pacemaker
      optimization using A-pacing at 60 bpm, optimal atrioventricular (AV) delay was
      found to be 290 ms by both pulsed wave (PW) echo Doppler as well as by the
      simultaneously measured radial artery pulse waveform analysis by tonometry. No
      discernable atrial mechanical activity was visible despite presence of sinus
      rhythm up to an AV delay of 190 ms. Further improvement in cardiac function and
      decrease in mechanical dyssynchrony was shown with VV optimization by tissue
      Doppler imaging (TDI). Our report emphasizes the need for individualized
      biventricular pacemaker optimization post-CRT and that concomitant assessment via
      radial artery pulse waveform analysis by tonometry along with PW and TDI may
      provide additional information during pacemaker programming to assist in
      pacemaker optimization.

PMID- 17534258
TI  - Primary percutaneous transluminal coronary angioplasty in the setting of
      multivessel disease.
AB  - Primary percutaneous coronary intervention of the culprit lesion is the treatment
      of choice for acute myocardial infarction, while treatment of the severe non
      culprit lesion is not indicated in the guidelines (Class III indication). More
      aggressive strategies that include initial treatment of the severe non culprit
      lesion may reduce the incidence of delayed occlusions in specific clinical
      settings. The two cases we describe support our point of view.

PMID- 17534259
TI  - Appropriateness of diagnostic and therapeutic pathways in patients with vascular
      disease.

PMID- 17534261
TI  - Delayed recovery of left ventricular systolic dysfunction: ''give time to medical
      therapy''.

PMID- 17534260
TI  - Off-label use of interventional cardiovascular devices.

PMID- 17534262
TI  - Multiple tachycardia forms occurring in a patient with Wolff-Parkinson-White
      syndrome and acute myocardial infarction.

PMID- 17534263
TI  - Anomalous left anterior descending coronary artery originating from the right
      coronary artery: a case report and review of the current literature.

PMID- 17534264
TI  - Heterotaxy syndrome with inversed atria-ventricles in a 50-year-old woman: review
      of the literature.

PMID- 17534265
TI  - Echocardiographic detection of an aortic tunnel between left sinus of Valsalva
      and coronary sinus.

PMID- 17534266
TI  - Characteristics of lentiviral vectors harboring the proximal promoter of the vav
      proto-oncogene: a weak and efficient promoter for gene therapy.
AB  - Recent published data have shown the efficacy of gene therapy treatments of
      certain monogenic diseases. Risks of insertional oncogenesis, however, indicate
      the necessity of developing new vectors with weaker or cell-restricted promoters
      to minimize the trans-activation activity of integrated proviruses. We have
      inserted the proximal promoter of the vav proto-oncogene into self-inactivating
      lentiviral vectors (vav-LVs) and investigated the expression pattern and
      therapeutic efficacy of these vectors. Compared with other LVs frequently used in
      gene therapy, vav-LVs mediated a weak, though homogeneous and stable, expression
      in in vitro-cultured cells. Transplantation experiments using transduced mouse
      bone marrow and human CD34(+) cells confirmed the stable activity of the promoter
      in vivo. To investigate whether the weak activity of this promoter was compatible
      with a therapeutic effect, a LV expressing the Fanconi anemia A (FANCA) gene was
      constructed (vav-FANCA LV). Although this vector induced a low expression of
      FANCA, compared to the expression induced by a LV harboring the spleen focus
      forming virus (SFFV) promoter, the two vectors corrected the phenotype of cells
      from a patient with FA-A with the same efficacy. We propose that self
      inactivating vectors harboring weak promoters, such as the vav promoter, will
      improve the safety of gene therapy and will be of particular interest for the
      treatment of diseases where a high expression of the transgene is not required.

PMID- 17534267
TI  - Antisense PNA accumulates in Escherichia coli and mediates a long post-antibiotic
      effect.
AB  - Antisense agents that target growth-essential genes display surprisingly potent
      bactericidal properties. In particular, peptide nucleic acid (PNA) and
      phosphorodiamidate morpholino oligomers linked to cationic carrier peptides are
      effective in time kill assays and as inhibitors of bacterial peritonitis in mice.
      It is unclear how these relatively large antimicrobials overcome stringent
      bacterial barriers and mediate killing. Here we determined the transit kinetics
      of peptide-PNAs and observed an accumulation of cell-associated PNA in
      Escherichia coli and slow efflux. An inhibitor of drug efflux pumps did not alter
      peptide-PNA potency, indicating a lack of active efflux from cells. Consistent
      with cell retention, the post-antibiotic effect (PAE) of the anti-acyl carrier
      protein (acpP) peptide-PNA was greater than 11 hours. Bacterial cell accumulation
      and a long PAE are properties of significant interest for antimicrobial
      development.

PMID- 17534268
TI  - Foxp3-expressing CD4(+)T cells under the control of INF-gamma promoter prevent
      diabetes in NOD mice.
AB  - Foxp3-transduced CD4(+)T-cells have been used for treating autoimmune diseases
      such as type I diabetes. However, while suppressing the activity of pathogenic T
      cells, they could suppress the activity of bystander T cells as well. Therefore
      more specific strategies need to be developed. We designed and tested a new
      strategy that involves converting pathogenic CD4(+)Th1 cells into regulatory T
      cells by lentiviral transduction with Foxp3 under the control of interferon-gamma
      (IFN-gamma) promoter (IgammaP-Foxp3). After transduction under the IgammaP
      control, Foxp3 expression in diabetic CD4(+)Th1 cells was favored. IgammaP-Foxp3
      transduced CD4(+)T cells were anergic in vitro to stimulation by antigen. The
      process of IgammaP-Foxp3-transduced CD4(+)T cells differentiating into Treg cells
      and Treg cells losing their phenotype and functions has the effect of
      significantly suppressing incidence and onset of diabetes and autoantigen
      specific T cell response, while increasing/maintaining endogenous Tregs in
      nonobese diabetic (NOD) mice recipients. In this manner, CD4(+)T cells of greater
      specificity were developed by transducing pathogenic CD4(+)Th1 cells with Foxp3
      under the control of IgammaP, in order to prevent diabetes in NOD mice. The
      findings of this study provide a basis for more reasonable regulatory T cells
      (Tregs)-based therapy, with autoimmunity being suppressed through indirect means
      known as "infectious tolerance".

PMID- 17534269
TI  - Can adults at high-risk of cardiovascular disease be identified by screening
      their children for risk factors?

PMID- 17534271
TI  - Can a network meta-analysis be used to determine the effect of antihypertensive
      drugs on the risk of incident diabetes?

PMID- 17534272
TI  - Growth hormone as an anti-aging therapy--do the benefits outweigh the risks?

PMID- 17534273
TI  - The metabolic syndrome as a risk factor in simultaneous kidney-pancreas
      transplantation.

PMID- 17534280
TI  - Opioid prescription in people with mental health problems--what is the way
      forward?

PMID- 17534281
TI  - Genetic research and genetic testing in Alzheimer's disease: a view from the
      bridge.

PMID- 17534282
TI  - An integrated approach to the management of IBS.

PMID- 17534283
TI  - Is primary precut endoscopic biliary sphincterotomy safe and effective?

PMID- 17534284
TI  - Should all colonoscopies be performed in the morning?

PMID- 17534285
TI  - Daily versus thrice-weekly hemodialysis for phosphorus control.

PMID- 17534286
TI  - Can partial auxiliary liver transplantation protect kidney grafts in highly
      sensitized patients?

PMID- 17534287
TI  - Does maintenance therapy with thalidomide benefit patients with multiple myeloma?

PMID- 17534288
TI  - Is stereotactic radiosurgery the best treatment option for patients with spinal
      metastases?

PMID- 17534289
TI  - Accelerated partial breast irradiation using multicatheter brachytherapy.

PMID- 17534290
TI  - Prescription of glucosamine for osteoarthritis: does it work and is it safe?

PMID- 17534291
TI  - The European League Against Rheumatism guidelines for early arthritis.

PMID- 17534295
TI  - Invalid methods.

PMID- 17534296
TI  - Confusing ratios.

PMID- 17534297
TI  - Illegal practice of dentistry.

PMID- 17534298
TI  - A divisive boat.

PMID- 17534299
TI  - Historical technicalities.

PMID- 17534300
TI  - Tail wagging the dog.

PMID- 17534301
TI  - Balance required.

PMID- 17534302
TI  - Tantamount to sacrosanct.

PMID- 17534303
TI  - A mix of appointments.

PMID- 17534304
TI  - Just a mouth ulcer?

PMID- 17534305
TI  - Trained circus animals.

PMID- 17534317
TI  - A way of dentistry.

PMID- 17534318
TI  - Creating a practice website.
AB  - A website is a window to the outside world. For a dental practice, it may be the
      first point of contact for a prospective new patient and will therefore provide
      them with their 'first impression'; this may be days or weeks before actually
      visiting the practice. This section considers the different ways of creating a
      dental practice website and lists some of the main dental website design
      companies. It also describes what factors make a successful website and offers
      advice on how to ensure that it complies with current regulations and
      recommendations.

PMID- 17534319
TI  - Necrotising fasciitis of the submandibular region; a complication of odontogenic
      origin.
AB  - Inadequate treatment or neglect of odontogenic infections can have serious
      consequences. The potential for spreading through fascial planes and
      intracranially can cause compromise of the airway and cavernous sinus thrombosis
      respectively. On rare occasions this can lead to a rapidly progressing
      necrotising fasciitis, with destruction of soft tissue, making reconstruction
      difficult. Antibiotic administration without removal of the cause is inadequate
      and can complicate subsequent management. We report the presentation and
      successful management of a 13-year-old boy, who developed necrotising fasciitis
      in the submandibular region as a result of inadequate initial treatment of a
      carious, lower molar resulting in significant skin and soft tissue loss.

PMID- 17534326
TI  - Special Care Dentistry: a professional challenge.
AB  - As a profession we have a responsibility to ensure that the oral health needs of
      individuals and groups who have a physical, sensory, intellectual, medical,
      emotional or social impairment or disability are met. In the UK, over 200,000
      adults have profound learning disabilities and/or complex medical conditions.
      Adults with a disability often have poorer oral health, poorer health outcomes
      and poorer access to services than the rest of the population. This paper
      examines the need for Special Care Dentistry based on a review of published
      literature, surveys and health policy, and suggests how services might be
      delivered in the future. Existing models of good practice reveal that established
      clinicians working in this field have a patient base of between 850 and 1,500
      patients per year and work across primary care and hospital settings, liaising
      with colleagues in health, social services and the voluntary sector to ensure
      integrated health care planning. On this basis, a conservative estimate of 133
      specialists is suggested for the future, working in networks with Dentists with
      Special Interests (DwSIs) and primary dental care practitioners. A skilled
      workforce that can address the wider needs of people requiring Special Care
      Dentistry should be formally recognised and developed within the UK to ensure
      that the needs of the most vulnerable sections of the community are addressed in
      future.

PMID- 17534353
TI  - Advancing the spark.

PMID- 17534347
TI  - The management of postoperative hemorrhage after laparoscopic renal and adrenal
      surgery.

PMID- 17534354
TI  - Lack of support for an association between CLEC4M homozygosity and protection
      against SARS coronavirus infection.

PMID- 17534355
TI  - Lack of support for an association between CLEC4M homozygosity and protection
      against SARS coronavirus infection.

PMID- 17534357
TI  - DNA double-strand breaks are not sufficient to initiate recruitment of TRF2.

PMID- 17534360
TI  - Ribonucleotide reductase and mitochondrial DNA synthesis.

PMID- 17534361
TI  - Evolutionary conservation in myoblast fusion.

PMID- 17534362
TI  - From fused toes in mice to human obesity.

PMID- 17534363
TI  - Scarce but scary.

PMID- 17534364
TI  - 'Unleashed' natural killers hinder HIV.

PMID- 17534367
TI  - Using FlyAtlas to identify better Drosophila melanogaster models of human
      disease.
AB  - FlyAtlas, a new online resource, provides the most comprehensive view yet of
      expression in multiple tissues of Drosophila melanogaster. Meta-analysis of the
      data shows that a significant fraction of the genome is expressed with great
      tissue specificity in the adult, demonstrating the need for the functional
      genomic community to embrace a wide range of functional phenotypes. Well-known
      developmental genes are often reused in surprising tissues in the adult,
      suggesting new functions. The homologs of many human genetic disease loci show
      selective expression in the Drosophila tissues analogous to the affected human
      tissues, providing a useful filter for potential candidate genes. Additionally,
      the contributions of each tissue to the whole-fly array signal can be calculated,
      demonstrating the limitations of whole-organism approaches to functional genomics
      and allowing modeling of a simple tissue fractionation procedure that should
      improve detection of weak or tissue-specific signals.

PMID- 17534374
TI  - Linkage disequilibrium analysis of two genes mapping on OFC3: PVR and PVRL2.
AB  - Clefts of the lip with or without cleft palate (CL/P) are one of the most common
      birth defects, occurring in 1/700-1/1,000 infants born alive. The nature of the
      genetic contribution is still to be clarified; however, some chromosome regions
      and candidate genes have been proposed for this malformation. Recently, a couple
      of genes, PVR and PVRL2, mapping in the candidate region OFC3 on chromosome
      19q13.31, have been investigated because of their homology to PVRL1, a gene
      previously shown to cause the Margarita Island CL/P-ectodermal dysplasia
      syndrome. In the present work, we investigated PVR and PVRL2 genes by family
      based linkage disequilibrium analysis using a sample collected from the Italian
      population. In contrast to previous analyses on other populations, we could not
      find any statistically significant association between the markers alleles and
      non-syndromic clefting.

PMID- 17534375
TI  - How can genetic tests be evaluated for clinical use? Experience of the UK Genetic
      Testing Network.
AB  - The UK Department of Health supported the establishment of the UK Genetic Testing
      Network (UKGTN) in 2002. The UKGTN is a collaborative network of NHS molecular
      genetic laboratories that offer tests for human single gene germ-line disorders.
      Its objective is to provide high quality and equitable services for patients and
      their families who require genetic advice, diagnosis and management. The UKGTN
      has developed a 'Gene Dossier' process to evaluate genetic tests and recommend
      which tests will be provided by the National Health Service. This paper describes
      the UKGTN organisation and the 'Gene Dossier' process. A brief review of the
      UKGTN genetic test evaluation experience is presented.

PMID- 17534376
TI  - Confirmation of associations between ion channel gene SNPs and QTc interval
      duration in healthy subjects.
AB  - Population-based association studies have identified several polymorphic variants
      in genes encoding ion channel subunits associated with the electrocardiographic
      heart-rate-corrected QT (QTc) length in healthy populations of Caucasian origin
      (KCNH2 rs1,805,123 (K897 T) and rs3,815,459, SCN5A rs1,805,126 (D1,819D), 1,141-3
      C>A, rs1,805,124 (H558R), and IVS24+116 G>A, KCNQ1 rs757,092, KCNE1 IVS2-128 G>A
      and rs1,805,127 (G38S), and KCNE2 rs2,234,916 (T8A)). However, few of these
      results have been replicated in independent populations. We tested the
      association of SNPs KCNQ1 rs757,092, KCNH2 rs3,815,459, SCN5A IVS24+116 G>A,
      KCNE1 IVS2-128 G>A and KCNE2 rs2,234,916 with QTc length in two groups of 200
      subjects presenting the shortest and the longest QTc from a cohort of 2,008
      healthy subjects. All polymorphisms were in Hardy-Weinberg equilibrium in both
      groups. The minor allele SCN5A IVS24+116 A was more frequent in the group of
      subjects with the shortest QTc, whereas the minor alleles KCNQ1 rs757,092 G and
      KCNH2 rs3,815,459 A were more frequent in the group with the longest QTc. There
      was no significant difference for KCNE1 IVS2-128 G>A and KCNE2 rs2,234,916
      between the two groups. Haplotype analysis showed a twofold increased risk of QTc
      lengthening for carriers of the haplotype, combining alleles C and A of the two
      common KCNE1 SNPs, IVS2-129 C>T (rs2,236,609) and rs1,805,127 (G38S),
      respectively. In conclusion, our study confirms the reported associations between
      QTc length and KCNQ1 rs757,092 and KCNH2 rs3,815,459.

PMID- 17534377
TI  - The MRE11/RAD50/NBS1 complex destabilization in Lynch-syndrome patients.
AB  - Lynch syndrome is an inherited disease leading to the development predominantly
      of colorectal cancer (CRC). The crucial cause is malfunction of DNA mismatch
      repair that is characterized by high level of microsatellite instability;
      however, new knowledge of two MSI modes (types A and B) suggests a more complex
      molecular basis of this syndrome. To investigate, whether the extensive
      alterations in individual MSI markers (type B) can indicate the potential
      deficiency of DNA double-strand break (DSB) repair in Lynch-syndrome-related
      tumours, we evaluated the MSI type and alterations in the MRE11 and RAD50 repeats
      that are associated with the reduced protein expression and functional impairment
      of the MRE11-RAD50-NBS1 (MRN) complex. Of 27 CRCs, 21 samples manifested type B
      in at least one MSI+ marker. From type B tumours, the genetic alterations were
      identified in 16 (76%) samples; seven, one and eight cases manifested mutations
      in MRE11, RAD50 and both genes, respectively. However, predominantly biallelic
      MRE11 alterations with simultaneously developed RAD50 mutations impaired the
      protein expressions with different intensity and location in tumour. Of six
      tumours presenting changes <or=6 bp (type A), in four samples identical
      alterations and protein expressions were observed. Moreover, in two patients with
      different MSI types germline insertions in the MRE11(T)(11) were found. Overall,
      our findings indicate the absence of significant association between type B MSI
      and MRE11 or RAD50 mutations in tumours of Lynch-syndrome patients, but a subset
      of them manifested causal mutations for MRN destabilization that could lead to
      the additional defect in DSB repair.

PMID- 17534378
TI  - Surgical adrenalectomy with diurnal corticosterone replacement slows escalation
      and prevents the augmentation of cocaine-induced reinstatement in rats self
      administering cocaine under long-access conditions.
AB  - The loss of control over cocaine use and persistently heightened susceptibility
      to drug relapse that define human cocaine addiction are consequences of drug
      induced neuroplasticity and can be studied in rats self-administering cocaine
      under conditions of daily long access (LgA) as escalating patterns of drug intake
      and heightened susceptibility to reinstatement. This study investigated the
      potential contribution of elevated glucocorticoids at the time of LgA cocaine
      self-administration (SA) to these behavioral indices of addiction-related
      neuroplasticity. Rats provided 14 days of 6-h access (LgA) to cocaine showed a
      progressive escalation of SA and were more susceptible to cocaine-induced
      reinstatement (10 mg/kg, i.p.) compared to rats self-administering under short
      access (ShA; 2 h) conditions. A surgical adrenalectomy and corticosterone
      replacement (ADX/C) regimen that eliminated SA-induced increases in
      corticosterone (CORT) while maintaining the diurnal pattern of secretion failed
      to alter SA or reinstatement in ShA rats but slowed escalation and attenuated
      later reinstatement in LgA rats when applied before but not after chronic LgA SA
      testing. Although the contribution of other adrenal hormones cannot be ruled out,
      these data suggest that elevated glucocorticoids at the time of cocaine exposure
      may be required for the effects of LgA SA on cocaine intake and later
      reinstatement. The inability of daily CORT administration before daily ShA SA, at
      a dose that reproduced the response during LgA SA, to mimic the effects of LgA SA
      suggests that elevated glucocorticoids during SA may play a permissive role in
      cocaine-induced neuroplasticity that contributes to addiction.

PMID- 17534379
TI  - Selective effects of cholinergic modulation on task performance during selective
      attention.
AB  - The cholinergic neurotransmitter system is critically linked to cognitive
      functions including attention. The current studies were designed to evaluate the
      effect of a cholinergic agonist and an antagonist on performance during a
      selective visual attention task where the inherent salience of
      attended/unattended stimuli was modulated. Two randomized, placebo-controlled,
      crossover studies were performed, one (n=9) with the anticholinesterase
      physostigmine (1.0 mg/h), and the other (n=30) with the anticholinergic
      scopolamine (0.4 mc/kg). During the task, two double-exposure pictures of faces
      and houses were presented side by side. Subjects were cued to attend to either
      the face or the house component of the stimuli, and were instructed to perform a
      matching task with the two exemplars from the attended category. The cue changed
      every 4-7 trials to instruct subjects to shift attention from one stimulus
      component to the other. During placebo in both studies, reaction time (RT)
      associated with the first trial following a cued shift in attention was longer
      than RT associated with later trials (p<0.05); RT also was significantly longer
      when attending to houses than to faces (p<0.05). Physostigmine decreased RT
      relative to placebo preferentially during trials greater than one (p<0.05), with
      no change during trial one; and decreased RT preferentially during the attention
      to houses condition (p<0.05) vs attention to faces. Scopolamine increased RT
      relative to placebo selectively during trials greater than one (p<0.05), and
      preferentially increased RT during the attention to faces condition (p<0.05). The
      results suggest that enhancement or impairment of cholinergic activity
      preferentially influences the maintenance of selective attention (ie trials
      greater than 1). Moreover, effects of cholinergic manipulation depend on the
      selective attention condition (ie faces vs houses), which may suggest that
      cholinergic activity interacts with stimulus salience. The findings are discussed
      within the context of the role of acetylcholine both in stimulus processing and
      stimulus salience, and in establishing attention biases through top-down and
      bottom-up mechanisms of attention.

PMID- 17534380
TI  - Self-administration of intravenous nicotine in male and female cigarette smokers.
AB  - Although nicotine is the main addictive chemical in tobacco, there have been few
      studies of pure nicotine self-administration in humans. The goal of this study
      was to test the parameters of an intravenous (IV) nicotine self-administration
      model using nicotine doses presumed to be within the range of those of average
      intake from cigarette smoking. Six male and four female smokers participated in a
      double-blind, placebo-controlled, crossover study, which consisted of one
      adaptation and three experimental sessions. In each experimental session,
      subjects were randomly assigned to one of the three doses of nicotine (0.1, 0.4,
      or 0.7 mg). The lowest nicotine dose, 0.1 mg, was chosen to be approximately half
      the amount of nicotine inhaled from one puff of a cigarette. During each
      experimental session, subjects first sampled the assigned nicotine dose and
      placebo and then had the opportunity to choose between nicotine and placebo for a
      total of six choices over a 90-min period. Out of six options, the average (SEM)
      number of nicotine choices were 3.0 (0.48) for 0.1 mg, 4.7 (0.48) for 0.4 mg and
      4.5 (0.46) for 0.7 mg, indicating a significant effect of nicotine dose on
      nicotine choice. Both the 0.4 and 0.7, but not the 0.1 mg, nicotine doses were
      preferred to placebo. These higher doses also produced increases in heart rate,
      blood pressure, and ratings of drug liking and high. Overall, these findings
      indicate that smokers chose both the 0.4 and the 0.7 mg nicotine doses over
      placebo. Our model may be useful in the evaluation of the effects of both
      behavioral and pharmacological manipulations on nicotine self-administration in
      humans.

PMID- 17534381
TI  - The population genetics of a solitary oligolectic sweat bee, Lasioglossum
      (Sphecodogastra) oenotherae (Hymenoptera: Halictidae).
AB  - Strong evidence exists for global declines in pollinator populations. Data on the
      population genetics of solitary bees, especially diet specialists, are generally
      lacking. We studied the population genetics of the oligolectic bee Lasioglossum
      oenotherae, a specialist on the pollen of evening primrose (Onagraceae), by
      genotyping 455 females from 15 populations across the bee's North American range
      at six hyper-variable microsatellite loci. We found significant levels of genetic
      differentiation between populations, even at small geographic scales, as well as
      significant patterns of isolation by distance. However, using multilocus genotype
      assignment tests, we detected 11 first-generation migrants indicating that L.
      oenotherae's sub-populations are experiencing ongoing gene flow. Southern
      populations of L. oenotherae were significantly more likely to deviate from Hardy
      Weinberg equilibrium and from genotypic equilibrium, suggesting regional
      differences in gene flow and/or drift and inbreeding. Short-term N(e) estimated
      using temporal changes in allele frequencies in several populations ranged from
      approximately 223 to 960. We discuss our findings in terms of the conservation
      genetics of specialist pollinators, a group of considerable ecological
      importance.

PMID- 17534382
TI  - The biogeography and population genetics of neotropical vector species.
AB  - Phylogenetic and population genetic data support the Pliocene or Pleistocene
      divergences of the co-distributed hematophagous insect vectors, the sand fly
      Lutzomyia longipalpis s.l., the mosquitoes Anopheles darlingi and A. albitarsis
      s.l., and the triatomines Rhodnius prolixus and R. robustus. We examined patterns
      of divergence and distribution in relation to three hypotheses of neotropical
      diversification: Miocene/Pliocene marine incursion, Pliocene/Pleistocene riverine
      barriers and Pleistocene refugia. Only R. prolixus has a pattern concordant with
      the refugia hypothesis, and R. robustus conforms to the marine incursion
      predictions. A. darlingi partially fits the refugia hypothesis. For L.
      longipalpis s.l. and A. albitarsis s.l., elements of both incursion and refugia
      hypotheses seem to fit, suggesting perhaps an interaction of factors determining
      their distribution patterns.

PMID- 17534383
TI  - Selection on MHC: a matter of form over function.

PMID- 17534384
TI  - Identification of human urinary metabolites of acetochlor in exposed herbicide
      applicators by high-performance liquid chromatography-tandem mass spectrometry.
AB  - Acetochlor is a preemergent chloroacetanilide herbicide used to control annual
      grasses and small-seeded broadleaf weeds. It is the second most abundantly
      applied herbicide on corn crops in the United States; however, human metabolites
      associated with known exposure to acetochlor have not been positively identified
      and confirmed. We positively identified acetochlor mercapturate (ACM) as a
      metabolite of acetochlor in urine samples collected during a 24-h period from
      custom (commercial) applicators who had applied acetochlor on either the day of
      or the day before urine collection. Concentrations in applicator urine samples
      ranged from 0.5 to 449 microg/l (0.3-121 microg/g creatinine). We found that ACM
      accounted for as much as 42% of the total acetochlor-derived metabolites;
      however, as the exposure level decreased (based on total acetochlor metabolite
      level), ACM became a less abundant metabolite of acetochlor (<17%). Unmetabolized
      acetochlor was also measured in the urine samples analyzed. At high exposures
      (classified as >100 microg/l), acetochlor accounted for about 0.8% of the total
      excreted acetochlor metabolites (approximately 2% of the ACM concentrations). At
      lower exposures (classified as ACM<10 microg/l), ACM and acetochlor
      concentrations were similar. Additionally, we tentatively identified another
      acetochlor metabolite that appeared to be important at low levels of exposure.

PMID- 17534385
TI  - The impact of magnetic resonance imaging-detected white matter hyperintensities
      on longitudinal changes in regional cerebral blood flow.
AB  - White matter hyperintensities are frequently detected on cranial magnetic
      resonance imaging (MRI) scans of older adults. Given the presumed ischemic
      contribution to the etiology of these lesions and the posited import of resting
      brain activity on cognitive function, we hypothesized that longitudinal changes
      in MRI-detected white matter disease, and its severity at a given time point,
      would be associated with changes in regional cerebral blood flow (rCBF) over
      time. We evaluated MRI scans and resting H(2)(15)O positron emission tomographic
      rCBF at baseline and after an average of 7.7-year follow-up in Baltimore
      Longitudinal Study of Aging participants without dementia. Differences in
      patterns of rCBF were evident at baseline and at follow-up between the group of
      subjects showing increased white matter disease over the 8-year interval compared
      with the group with stable white matter ratings. Furthermore, longitudinal
      changes over time in rCBF also differed between the two groups. Specifically, the
      group with progressive white matter abnormalities showed greater increase in the
      right inferior temporal gyrus/fusiform gyrus, right anterior cingulate, and the
      rostral aspect of the left superior temporal gyrus. Regions of greater
      longitudinal decrease in this group were evident in the right inferior parietal
      lobule and at the right occipital pole. Changes in white matter disease over time
      and its severity at any given time are associated significantly with both cross
      sectional and longitudinal patterns of rCBF. The longitudinal increases may
      reflect cortical compensation mechanisms for reduced efficacy of interregional
      neural communications that result from white matter deterioration.

PMID- 17534387
TI  - Targeted therapies: the answer to individualized treatment?

PMID- 17534386
TI  - Association of integrin alpha2 gene variants with ischemic stroke.
AB  - Genetic variants in the gene encoding integrin alpha2 (ITGA2) have been reported
      to be associated with an increased risk for ischemic stroke. The purpose of this
      study was to investigate the association between haplotype-tagging single
      nucleotide polymorphisms (tSNPs) in ITGA2 and risk of ischemic stroke in a
      collection of North American stroke cases and controls. The study included 484
      cases and 263 controls. Thirteen tSNPs were genotyped. Association tests at and
      across each tSNP were performed, including haplotype association analysis.
      Secondary analyses considered stroke subtypes on the basis of Trial of Org 10172
      in Acute Stroke Treatment (TOAST) criteria. We observed significant association
      between tSNP rs3756541 (additive model, odds ratio (OR), 1.49; 95% confidence
      interval (CI), 1.11 to 2.04; P=0.009) and disease and a trend toward association
      at rs2303124 (recessive model, OR, 1.56; 95% CI, 1.05 to 2.33; P=0.03). These
      associations remained significant in the haplotype analyses. The associated tSNPs
      did not distinguish stroke etiology after application of TOAST criteria. Our
      results suggest that genetic variability within ITGA2 may confer risk for
      ischemic stroke independent of conventional risk factors. These results provide
      additional support for a role for platelet receptor genes in the pathogenesis of
      ischemic stroke of diverse subtypes.

PMID- 17534388
TI  - Accelerated partial breast irradiation using the MammoSite device.

PMID- 17534389
TI  - External-beam-based partial breast irradiation.

PMID- 17534390
TI  - Malignant pleural mesothelioma: current concepts in treatment.
AB  - Malignant pleural mesothelioma (MPM) is a primary and locally aggressive tumor of
      the pleura. A well defined causal relationship with asbestos exposure, and an
      overwhelming media interest in the use of asbestos in industrialized countries
      after World War II, has produced a high level of awareness of this disease. With
      a peak incidence of MPM expected in Europe, Australia, and the US within the next
      15 years, and the failure of current treatment approaches to offer long-term
      survival and improve quality of life, new therapeutic regimens are warranted. The
      effects of surgery in terms of survival and symptomatic relief have yet to be
      defined because of a lack of randomized trials. The role of radiotherapy in the
      treatment of MPM remains controversial, as the radiosensitivity of malignant
      mesothelial cells is modest. MPM response to chemotherapy is comparatively poor.
      The combination of pemetrexed and cisplatin chemotherapy has achieved the best
      objective responses. Presently, a multimodal approach is considered to be the
      cornerstone of treatment of MPM. Important ongoing international and national
      trials are addressing the roles of chemotherapy (e.g. the EAP and MS01 trial),
      radical surgery (e.g. the MARS trial) and radiotherapy (e.g. the SAKK group phase
      III study).

PMID- 17534391
TI  - Surgery insight: radical vaginal trachelectomy as a method of fertility
      preservation for cervical cancer.
AB  - Over the past decade, the treatment of cervical cancer has evolved with an
      increased emphasis on preservation of fertility. There has been a gradual
      abandonment of radical surgical procedures in favor of more conservative
      techniques in an effort to decrease morbidity and preserve fertility without
      compromising overall survival. Radical vaginal trachelectomy (RVT) with
      laparoscopic pelvic lymphadenectomy is a fertility-preserving procedure that has
      recently gained worldwide acceptance as a method of surgically treating small
      invasive cancers of the cervix. Since the original description of RVT by Daniel
      Dargent in 1994, over 500 cases of utilization of this technique have been
      reported in the literature, with over 100 live births reported following this
      procedure. The morbidity associated with RVT is low, with a tumor recurrence rate
      of 5% and a mortality rate of 3%. The current literature indicates no difference
      in the rate of recurrence with this technique compared with radical hysterectomy
      when proper selection criteria are used. Combining RVT with laparoscopic sentinel
      lymph-node biopsy can further reduce the duration, extent, and complications of
      surgery.

PMID- 17534392
TI  - Mechanisms of disease: genetic predictors of response to treatment in brain
      tumors.
AB  - Brain tumors are currently diagnosed on the basis of their histology. The most
      common types in adults are astrocytomas, oligodendrogliomas and oligoastrocytomas
      or mixed tumors, which almost invariably lead to death. Improvements in outcome
      have been elusive despite intensive research. Recent findings indicate that
      response to conventional therapy, at least in some cases, correlates better with
      genetic characteristics than histopathology. An understanding of the molecular
      mechanisms that underlie the malignant phenotype of gliomas also provides the
      possibility of rational design of molecularly targeted therapies. This approach
      has proved successful in other areas of oncology. As many tumors have the same
      types of molecular abnormalities, molecular targeted therapies developed for
      nonbrain tumor types might be adapted for the treatment of brain tumors. There
      are a number of unique problems involved in treating tumors in the brain that
      must be overcome. The genetic predictors of response to conventional therapies,
      the genes and cellular mechanisms involved in glioma development, and potential
      therapeutic targets are reviewed. The possibility of designing tailored molecular
      therapy based on the molecular characteristics of the tumors is also explored.

PMID- 17534393
TI  - Neoadjuvant cisplatin and radical cesarean hysterectomy for cervical cancer in
      pregnancy.
AB  - BACKGROUND: A 28-year-old Hispanic gravida 1 was found to have a 4-5 cm cervical
      mass when she presented at 23 weeks gestation. On pelvic examination, the tumor
      was shown to encompass the entire circumference of the cervix without parametrial
      or vaginal involvement. A biopsy of the mass revealed a poorly differentiated
      squamous-cell carcinoma of the cervix. An MRI study of the abdomen and pelvis
      showed a 4 cm cervical mass that was suspicious for left parametrial and
      rectovaginal septal involvement. No hydronephrosis or lymphadenopathy was noted.
      The patient elected to proceed with her pregnancy. INVESTIGATIONS: General
      physical and gynecological examinations, cervical biopsy, pelvic and obstetric
      ultrasound, histopathological examination, MRI of the abdomen and pelvis without
      and with gadolinium, neonatal hearing test and renal function studies. DIAGNOSIS:
      Poorly differentiated stage IB2 squamous-cell carcinoma of the cervix with MRI
      imaging suggestive of parametrial and rectovaginal septal involvement.
      MANAGEMENT: Neoadjuvant chemotherapy using weekly cisplatin from 24 to 30 weeks,
      bed rest and oral terbutaline at 31 weeks because of premature contractions, and
      a course of antenatal steroids to promote fetal lung maturity. At 33 weeks
      radical cesarean hysterectomy, bilateral pelvic and para-aortic lymphadenectomy
      and bilateral ovarian transposition were carried out, followed by adjuvant pelvic
      radiation therapy with cisplatin chemosensitization 4 weeks postpartum.

PMID- 17534394
TI  - Cardiovascular diseases in China.
AB  - Statistics from the National Population Census of China revealed a significant
      increase in the Chinese population, from 590 million in 1953 to 1.26 billion in
      2000. The average life expectancy increased to 71.4 years in 2000 compared with
      the expectancy of 68.6 years a decade before. World Health Organization
      statistics on the death rate for total cardiovascular disease, coronary heart
      disease, and stroke in men and women aged 35-74 years revealed discrepancies
      between rural and urban parts of China. The China Multicenter Collaborative Study
      of Cardiovascular Epidemiology indicated that cardiovascular disease was the
      major cause of death for both men and women, with stroke accounting for over 40%
      of deaths. Ischemia was shown to be the most common subtype of stroke in both
      sexes. Smoking was an independent risk factor for cardiovascular disease. The
      World Health Organization reported that the death rate attributable to tobacco
      was 6.0% worldwide and 9.2% in China in 1990. The latter is projected to reach
      16.6% by 2020. In China, the prevalence of hypertension and diabetes mellitus,
      the two key risk factors of cardiovascular disease, have also increased
      significantly in the past 20 years. In addition, elevated blood pressure and
      plasma cholesterol were two important determinants of increased cardiovascular
      disease in eastern Asia. These studies indicate that an integrated management of
      comprehensive risk is urgently required to address China's increasing
      cardiovascular disease burden.

PMID- 17534395
TI  - The effect of locally delivered c-myc antisense oligonucleotides combined with
      intravascular brachytherapy of 188Re liquid-filled balloon therapy on vascular
      smooth muscle cell proliferation in rabbit iliac arteries after injury with a
      balloon catheter.
AB  - Poststenting restenosis is a significant clinical problem that involves vascular
      smooth muscle cell (VSMC) proliferation. We primarily investigated the effect of
      c-myc antisense oligodeoxynucleotides (ASODNs) combined with 188Re radiation
      therapy on VSMC proliferation in rabbit common iliac arteries injured by the
      porous balloon catheter to explore the therapeutic potential of the combined
      therapy for the prevention of restenosis. The iliac arteries in rabbits were
      injured with balloon catheters, and radiation therapy was carried out with a 2.5
      mm balloon catheter filled with 188Re (8 or 15 Gy), and ASODNs (300 microg) were
      applied to the adventitia introduced using a pluronic gel releasing system and a
      lipofectin delivery system. After 3 weeks, the animals were killed and defined
      segments of arteries were sectioned. The histological sections were stained using
      alpha-actin immunohistochemistry staining. The positive alpha-actin ratios were
      calculated and analyzed statistically among groups. In contrast to the rate of
      alpha-actin positive cell staining in the control group, the rate of alpha-actin
      positive cell staining did not decrease (P > 0.05) in the 188Re-irradiated group
      (8 Gy). However, in the ASODN-treated group, the 188Re-irradiated group (15 Gy),
      and the combined ASODN - 188Reirradiated groups (8 or 15 Gy), the ratios had
      markedly decreased (P < 0.01). The effect of the combined group (ASODNs + 188Re
      (15 Gy)) provided the lowest level of alpha-actin positive cell staining (P <
      0.01). The ASODNs (300 microg) effectively decreased VSMC poliferation. The
      effect of the 188Re radiation on the VSMCs depended on the dosage. The ASODNs
      (300 microg) and combined 188Re irradiation effectively lowered VSMC
      proliferation, and the effect was better than that achieved with any other
      treatment.

PMID- 17534396
TI  - Mechanism of saikosaponin-d in the regulation of rat mesangial cell proliferation
      and synthesis of extracellular matrix proteins.
AB  - Glomerulosclerosis is a common disorder in many types of chronic kidney diseases.
      Previous studies have shown that glomerular mesangial cells (MCs) play an
      important role in the pathogenesis of glomerulosclerosis. The ability of
      saikosaponin-d (SSd) to reduce the damage of kidney in progressive
      glomerulosclerosis has been demonstrated. In this study, the effects of
      saikosaponin-d on MC proliferation and synthesis of extracellular matrix proteins
      were investigated. Rat MCs were isolated from Wistar rats and cultured in
      Dulbecco's modified Eagle's medium. MCs were challenged with lipopolysacchorides
      and incubated with different concentrations of SSd. Cell proliferation and
      cytotoxicity were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide (MTT), flow cytometry, and lactate dehydrogenase
      assays. Type IV collagen, fibronectin, and TGF-beta1 in the conditioned medium
      were measured. The expression of cyclin-dependent kinase 4, c-Jun, and c-Fos was
      determined by immunohistochemistry. At a concentration of 4 microg/mL or lower,
      SSd inhibited MC proliferation but did not cause cell death. SSd also inhibited
      lipopolysaccharide-induced secretion of type IV collagen, fibronectin, and TGF
      beta1 in MCs. Additionally, SSd reduced the expression of CDK4, c-Jun, and c-Fos
      in MCs. We conclude that SSd inhibited MC proliferation and synthesis of
      extracullular matrix proteins through the downregulation of the CDK4, c-Jun, and
      c-Fos genes.

PMID- 17534397
TI  - The effect of delayed preconditioning on connexin 43 in ischemic myocardium.
AB  - The objective of this study is to investigate the effects of preconditioning on
      the restoration and distribution of connexin 43 (Cx43) in ischemic myocardium in
      dogs. In this study, 40 dogs were randomly divided into 5 groups of 8 as follows:
      control, 0hI-R (ischemia followed by 0 h reperfusion), 6hI-R (ischemia followed
      by 6 h reperfusion), 24hI-R (ischemia followed by 24 h reperfusion), and 48hI-R
      (ischemia followed by 48 h reperfusion). Four dogs in each group were
      preconditioned with brief episodes of ischemia prior to the respective treatments
      and were referred as the PC groups, while the other 4 were not preconditioned and
      were referred as the nonPC groups. The myocardial ischemia was induced by
      ligation of the left anterior descending coronary artery. The expression and
      distribution of Cx43 within the ischemic myocardium were measured by Western blot
      analysis and studied using laser confocal microscopy using a double-label
      immunohistochemistry technique. Compared with the control group, there was a
      significant reduction in Cx43 content within ischemic myocardium of all test
      groups both with and without PC (P < 0.01, P < 0.05). Within the 0hI-R, 6hI-R,
      and 24hI-R groups, an insignificant difference was found in the expression and
      distribution of Cx43 within the ischemic region between the PC and the nonPC
      groups. However, in the 48hI-R group, the area and intensity of Cx43 staining
      within the ischemic region of the PC dogs were significantly larger and more
      intense than those of the nonPC dogs (P < 0.01), and the ratio of Cx43 pixel
      density in intercalated disk areas to that in side-to-side junction areas in the
      PC dogs was significantly greater than that in nonPC dogs (P < 0.01). Our results
      suggest that preconditioning has a significant effect on the restoration and
      distribution of Cx43 in the ischemic myocardium in dogs after 48 h. Hence,
      preconditioning may be a plausible cause for the observed reductions in cardiac
      arrhythmias.

PMID- 17534398
TI  - Effects of N-n-butyl haloperidol iodide on L-type calcium channels and
      intracellular free calcium in rat ventricular myocytes.
AB  - The ability of N-n-butyl haloperidol iodide (F2) to cause vasodilation, and
      thereby produce a cardioprotective effect, has been well documented. The aim of
      this study was to investigate whether F2 might act as a Ca2+ antagonist. Myocytes
      were obtained from rat heart, and the whole-cell patch-clamp technique was used
      to record Ca2+ current. Laser scanning confocal microscopy was used to measure
      intracellular free calcium ([Ca2+]i). The results obtained from this study
      demonstrate that F2 reduced calcium current (ICa) in a concentration-dependent
      manner with an IC50 of 1.19 micromol/L, upshifted the current-voltage curve of
      ICa, shifted the inactivation kinetics of ICa leftward, and slowed down the
      recovery of ICa from inactivation. F2 decreased the fluorescent intensity of
      [Ca2+]i elevation induced by KCl with an IC50 of 1.61 micromol/L, and had no
      effects on the intracellular calcium release induced by caffeine and inositol
      1,4,5-trisphosphate. These findings indicate that F2 may act as a calcium
      antagonist, which could account for its cardiovascular benefits.

PMID- 17534399
TI  - Saikosaponin-d attenuates the development of liver fibrosis by preventing
      hepatocyte injury.
AB  - Treatment of liver fibrosis and cirrhosis remains a challenging field. Hepatocyte
      injury and the activation of hepatic stellate cells are the 2 major events in the
      development of liver fibrosis and cirrhosis. It is known that several Chinese
      herbs have significant beneficial effects on the liver; therefore, the purpose of
      the present study was to investigate the therapeutic effect of saikosaponin-d
      (SSd) on liver fibrosis and cirrhosis. A rat model of liver fibrosis was
      established using the dimethylnitrosamine method. Liver tissue and serum were
      used to examine the effect of SSd on liver fibrosis. A hepatocyte culture was
      also used to investigate how SSd can protect hepatocytes from oxidative injury
      induced by carbon tetrachloride. The results showed that SSd significantly
      reduced collagen I deposition in the liver and alanine aminotransferase level in
      the serum. Moreover, SSd decreased the content of TGF-beta1 in the liver, which
      was significantly elevated after dimethylnitrosamine induced liver fibrosis.
      Furthermore, SSd was able to alleviate hepatocyte injury from oxidative stress.
      In conclusion, SSd could postpone the development of liver fibrosis by
      attenuating hepatocyte injury.

PMID- 17534400
TI  - Anti-CD3 scFv-B7.1 fusion protein expressed on the surface of HeLa cells provokes
      potent T-lymphocyte activation and cytotoxicity.
AB  - The targeting of tumor cells by cytotoxic T lymphocytes is a promising strategy
      for biotherapy, but T cells require 2 signals via the T-cell receptor - CD3
      complex and CD28 molecules for activation. To bridge the gap between cytotoxic T
      lymphocytes and tumor cells, our objective in this study was to describe the
      construction and the cell surface-anchored expression of a fusion protein, anti
      CD3 scFv-B7.1, derived from inserting a fusion gene encoding anti-CD3 scFv and
      the extra-cellular domain of B7.1 fused by the splicing by overlap extension
      method into a mammalian expression vector, pDisplay. Transfection of the
      recombinant vector by electroporation into HeLa cells resulted in the production
      of protein migrating at approximately 57 kDa under reducing conditions. The
      expressed fusion protein could bind to T lymphocytes and induce strong T-cell
      activation. Meanwhile, a potent cytotoxicity was induced in the mixed culture of
      T-cell-modified tumor cells in a 96 h methyl-thiazolyl-diphenyl tetrazolium
      bromide assay. Our results indicate that this bifunctional protein, through
      activating T lymphocytes to lyse homologous human carcinomas, may be of potential
      value for T-cell-based immunotherapeutical treatment protocols in vivo.

PMID- 17534401
TI  - Expression and bioactivity of recombinant segments of human perforin.
AB  - The aim of the study was to prepare an active recombinant human perforin by
      comparing 5 candidate segments of human perforin. Full-length perforin, MAC1 (28
      349 aa), MAC2 (166-369 aa), C-100, and N-60 of human perforin were selected as
      candidate active segments and designated, respectively, HP1, HP2, HP3, HP4, and
      HP5. The target genes were amplified by PCR and the products were individually
      subcloned into pGEM-T. The genes for HP1, HP2, HP3, and HP5 were subcloned into
      pET-DsbA, whereas pET-41a (+) was used as the expression vector of HP4. The
      fusion proteins were expressed in Escherichia coli BL21pLysS(DE3) and purified
      using nickel nitrilotriacetic acid (NTA) agarose affinity chromatography. The
      hemolysis microassay was used as an activity assay of fusion protein. From this
      study, we obtained the recombinant plasmids pGEM-T-HP1, -HP2, -HP3, -HP4 and 
      HP5, consisting of 1600, 960, 600, 300bp, and 180, respectively. From these
      recombinant plasmids, expression plasmids were successfully constructed and
      expressed in E. coli BL21pLysS(DE3). The resultant fusion proteins, affinity
      purified using Ni-NTA, were approximately 80, 58, 45, 44, and 30 kDa,
      respectively. The recombinant proteins were assayed for activity on hemolysis.
      HP2 and HP5 were the only recombinant proteins that were active in hemolysis, and
      the hemolytic function was concentration dependent. These results demonstrate
      that active recombinant forms of perforin can be synthesized in a prokaryote
      model. The recombinant N-60 and MAC1 (28-349 aa) of human perforin have the
      function of forming pores. Our study provides the experimental basis for further
      investigation on the application of perforin.

PMID- 17534402
TI  - A 27.368 kDa retinal reductase in New Zealand white rabbit liver cytosol encoded
      by the peroxisomal retinol dehydrogenase-reductase cDNA: purification and
      characterization of the enzyme.
AB  - We obtained a full-length cDNA based on a sequence deposited in GenBank
      (accession No. AB045133), annotated as rabbit peroxisomal NADP(H)-dependent
      retinol dehydrogenase-reductase (NDRD). The rabbit NDRD gene, like its mouse and
      human homologs, harbors 2 initiation sites, one of which theoretically encodes a
      29.6 kDa protein with 279 amino acids, and the other encodes a 27.4 kDa protein
      with 260 amino acids. The purification of a rabbit cytosolic retinol
      oxidoreductase with a subunit molecular mass of 34 kDa and an N terminus that is
      not completely identical to that of NDRD, has been reported. An enzyme
      responsible for the all-trans retinal reductase activity in the liver cytosol of
      New Zealand white rabbit was purified to homogeneity using differential
      centrifugation and successive chromatographic analyses. The subunit molecular
      mass of the purified enzyme, revealed by SDS-PAGE, was approximately 27 kDa. The
      intact molecular mass, measured by MALDI-TOF mass spectrometry, was 27.368 kDa.
      The 60 kDa relative mobility observed in size-exclusion chromatography indicates
      that the native protein probably exists as a dimer. The purified enzyme was
      positively confirmed to be the product of NDRD by peptide mass fingerprinting,
      tandem mass spectrometry, and N-terminal sequencing. Taken together, the results
      suggested that the native protein is truncated at the N terminus.

PMID- 17534403
TI  - Codon usage bias in Chlamydia trachomatis and the effect of codon modification in
      the MOMP gene on immune responses to vaccination.
AB  - Chlamydia trachomatis is a kind of obligate intracellular bacterial pathogen that
      causes ocular and sexually transmitted diseases. In this study, we analyzed the
      codon usage patterns of the C. trachomatis mouse pneumonitis biovar (MoPn) and
      Homo sapiens. We found large differences between MoPn and human codon usages. To
      enhance the expression of Chlamydia protein in mammalian cells, the DNA sequence
      encoding the major outer-membrane protein (MOMP) of MoPn was modified to
      substitute the human-preferred codons for rarely used codons. The huma-optimized
      MOMP gene was synthesized and cloned into the pcDNA3 vector, as was the wild-type
      MOMP gene. The protein expression levels of the human-optimized MOMP and wild
      type MOMP genes were compared. The experiments showed that the human-optimized
      MOMP gene produced significantly higher levels of MOMP protein than the wild-type
      MOMP, both in vitro and in vivo, but no obvious difference was observed in the
      levels of modified and native MOMP mRNA expression. The immunogenicity of the 2
      constructs was examined using BALB/c mice following intramuscular immunization.
      The results showed that the mice immunized with the human-optimized MOMP produced
      higher levels of antigen-specific IgG antibody and showed stronger delayed-type
      hypersensitivity reactions and proliferative T cell responses than those
      immunized with the wild-type MOMP. Antigen-specific stimulation of spleen cells
      obtained from human MOMP DNA immunized mice produced higher levels of interferon
      gamma than those obtained from wild-type MOMP DNA immunized mice. Taken together,
      the data show that human-optimized codon optimization can significantly enhance
      the gene expression and immunogenicity of the C. trachomatis MOMP DNA vaccine.

PMID- 17534404
TI  - The association of HLA-DRB1 alleles with rheumatoid arthritis in the Chinese
      Shantou population: a follow-up study.
AB  - We investigated the distribution of HLA-DRB1 alleles in a sample of the Chinese
      Shantou population, and explored the relationship between HLA-DRB1 alleles and
      the susceptibility and clinical features of rheumatoid arthritis (RA). We studied
      117 consecutive patients with RA and control groups, including 38 cases of
      systemic lupus erythematosus and 100 healthy individuals. HLA-DRB1 genotyping was
      performed using PCR with sequence-specific primers. HLA-DRB1*04 subtypes were
      detected using spot hybridization of PCR products with sequence-specific
      oligonucleotide probes. We compared the frequency of HLA-DRB1 alleles in healthy
      control patients with that in patients with RA. Patients with RA were evaluated
      for sex, age at disease onset, disease duration, extra-articular involvement,
      presence of autoantibodies, global functional status, and radiographic damage.
      The frequency of HLA-DRB1*04 was found to be significantly higher in RA patients
      than in healthy individuals (49.6% vs 18.0%, odds ratio = 4.478, P < 0.001). HLA
      DRB1*0405 was the most prominently associated subtype in RA patients (62.1% vs
      27.8%, odds ratio = 4.255, P = 0.011). Compared with the HLA-DRB1*04-negative RA
      group, the mean duration of RA in the HLA-DRB1*04-positive RA group was longer,
      and the mean age at disease onset was lower. A 2-9 year follow-up study was
      performed, and the risk factors associated with the radiographic progression of
      RA were determined. Logistic regression analysis revealed that only HLA-DRB1*04
      alleles were significantly associated with the radiographic progression of RA (B
      = 2.652, P = 0.018, Exp(B) = 14.182). Our observations indicated that the HLA
      DRB1*04 alleles, especially the subtype HLA-DRB1*0405, were significantly
      associated with RA susceptibility in the Chinese Shantou population. The HLA
      DRB1*04 alleles may be associated with the severity of RA.

PMID- 17534405
TI  - Isolation of a novel ras gene from Trichomonas vaginalis: a possible evolutionary
      ancestor of the Ras and Rap genes of higher eukaryotes.
AB  - The Ras subfamily proteins are small, monomeric GTP-binding proteins with vital
      roles in regulating eukaryotic signal transduction pathways. Gene duplication and
      divergence have been postulated as the mechanism by which such family members
      have evolved their specific functions. A cDNA clone of TvRsp was isolated and
      sequenced from a cDNA expression library of the primitive eukaryote Trichomonas
      vaginalis. The genomic DNA corresponding to the cDNA sequence was amplified by
      PCR and sequenced. Sequence analysis suggested that TvRsp was an intronless gene.
      This gene encoded a protein of 181 amino acids and contained the 5 conserved G
      domains that designated it as a Ras or Rap subfamily member. However, the deduced
      amino acid sequence shared only 34%-37% overall identity with other Ras subfamily
      members of different species, and the presence of motifs characteristic of both
      the Ras and Rap families of GTPase confused the familial classification of this
      gene. Phylogenetic analysis showed its origins at the divergence point of the
      Ras/Rap families and suggested that TvRsp was a possible evolutionary ancestral
      gene of the ras/rap genes of higher eukaryotes. This information was of
      importance not only from the perspective of understanding the evolution and
      diversity of eukaryotic signal transduction pathways but also in providing a
      framework by which to understand protein processing in the growth and
      differentiation of single-celled microorganisms.

PMID- 17534406
TI  - Physiological testosterone stimulates tissue plasminogen activator and tissue
      factor pathway inhibitor and inhibits plasminogen activator inhibitor type 1
      release in endothelial cells.
AB  - There is a striking gender difference in atherosclerotic vascular disease. For
      decades, testosterone was considered detrimental to the cardiovascular system.
      Recent studies, however, have presented some alternative results. The aim of this
      study was to evaluate the effect of testosterone, using physiological and
      supraphysiological concentrations, on antigen and mRNA levels of tissue
      plasminogen activator (tPA), plasminogen activator inhibitor type 1 (PAI-1), and
      tissue factor pathway inhibitor (TFPI) released by human umbilical vein
      endothelial cells and to investigate the cellular mechanism. Cells within 2-3
      passages were cultured in 25 cm(2) flasks or plated onto 96-well plates with a
      density of about 1 x 10(5) cells/mL as recommended. The cells were incubated in
      the presence or absence of testosterone (3, 30, 3 x 10(3), 3 x 10(4) nmol/L) for
      48 h. Levels of tPA, PAI-1, and TFPI antigen were assayed with ELISA kits.
      Reverse transcriptase PCR was carried out to detect tPA, PAI-1, and TFPI mRNA
      levels. Cells were incubated in androgen-receptor antagonist (flutamide 10
      micromol/L) or aromatase inhibitor (aminoglutethimide 50 micromol/L) for 3 h, and
      then the experiments were repeated. Testosterone at a physiologic concentration
      (30 nmol/L) increased the antigen levels of tPA and TFPI significantly (P <
      0.05). However, tPA and TFPI levels were markedly reduced (P < 0.05) at a larger
      dose (3 x 10(4) nmol/L). On the other hand, PAI-1 antigen levels decreased
      significantly at the testosterone concentrations ranging from 3 to 3 x 10(4)
      nmol/L (P < 0.05). The change in the levels of tPA and TFPI were reflected in the
      corresponding change in mRNA levels. Flutamide attenuated the effect of
      testosterone at physiological concentration (30 nmol/L). The results demonstrated
      that testosterone at physiological concentrations may have a beneficial influence
      on the haemostatic system through enhancement of anticoagulant activity,
      resulting from stimulation of TFPI and tPA expression and inhibition of PAI-1
      secretion by the endothelium.

PMID- 17534407
TI  - Adult asthmatics display exaggerated IFNgamma responses to human metapneumovirus
      and respiratory syncytial virus.
AB  - Human metapneumovirus and respiratory syncytial virus are RNA viruses associated
      with lower respiratory tract infections. Regular symptomatic re-infection and
      sequelae are common, particularly in individuals with pre-existing respiratory
      diseases, such as asthma. Our understanding of virus-dependent cytokine responses
      and potential differences between allergic asthmatics and non-asthmatics is
      limited. To test our hypothesis that adults with mild allergic asthma, the most
      common form of this disease, exhibit distinct pro-inflammatory responses, we
      developed a model using acute in vitro infection of fresh peripheral blood
      mononuclear cells. For both viruses, the production of innate-immunity-associated
      IL-6 and IL-10 was indistinguishable in the 2 populations. Type 1 cytokine
      production dominated adaptive immune responses in both asthmatic and non
      asthmatic individuals. Surprisingly, asthmatics exhibited stronger pro
      inflammatory IFNgamma production in response to human metapneumovirus than non
      asthmatic adults (p = 0.01), with a similar, but statistically nonsignificant
      trend in the respiratory-syncytial-virus-stimulated response. Neutralizing IL-10
      did not enhance the intensity of IFNgamma responses, demonstrating that this pro
      inflammatory bias is not counter-regulated by IL-10. Finally, anti-TLR4 blocked
      lipopolysaccharide, but not respiratory-syncytial-virus-driven cytokine
      production. Collectively, the data demonstrate that asthma is characterized by
      markedly stronger pro-inflammatory IFNgamma responses to pneumoviruses than their
      non-asthmatic counterparts. This distinctive pattern of viral immunity may
      contribute to a worsening of asthma symptoms during respiratory virus infections.

PMID- 17534408
TI  - QUASI analysis of the HIV-1 envelope sequences in the Los Alamos National
      Laboratory HIV sequence database: pattern and distribution of positive selection
      sites and their frequencies over years.
AB  - The envelope (env) protein of human immunodeficiency virus type 1 (HIV-1) plays a
      crucial role in virus entry and is a central target for HIV vaccine design. Using
      the QUASI program, we analyzed the conserved regions of all currently available
      env sequences in the Los Alamos National Laboratory HIV Sequence Database and
      identified positive selection (PS) sites that are likely to be restricted by host
      immune responses. We found that PS sites are dispersed across conserved regions
      of env sequence, and that the C3, C4, and C5 regions were the most targeted.
      Several regions were identified as being PS free and were mainly distributed in
      the C1 and C2 regions. When comparing individual QUASI PS site frequencies across
      clades and geographical regions with the overall frequency of the entire env
      database, the env sequences from North America showed significantly lower PS site
      frequency, while those from Asia were significantly higher using Student's t
      test. The QUASI PS site frequency of env proteins from viruses isolated from
      different years showed that the PS site frequencies of the env population
      increased over time. Our study provides an overview of PS sites across the
      conserved regions of HIV-1 env sequences.

PMID- 17534409
TI  - Reactive oxygen species and mitochondrial membrane potential are modulated during
      CDDP-induced apoptosis in EC-109 cells.
AB  - cis-Diamminedichloroplatinum (CDDP), commonly know as cisplatin, is a well known
      DNA-damaging agent, which is highly active in suppressing the proliferation of
      tumor cells. However, it is not clear that CDDP can induce growth inhibition of
      esophagus cancer cells. Using the cell line EC-109 from the esophagus, we found
      that CDDP would induce apoptotic responses. The addition of CDDP to cells led to
      the inhibition of growth in a time- and dose-dependent manner. CDDP generated
      reactive oxygen species (ROSs) in cells, which brought about a reduction in the
      intracellular mitochondrial transmembrane potential (Deltapsim), leading to
      apoptosis. Our findings demonstrate that ROSs, and the resulting oxidative
      stress, play a pivotal role in apoptosis. Preincubation of EC-109 cells with the
      hydrogen-peroxide-scavenging enzyme catalase partially inhibited the following:
      (i) the production of ROS; (ii) the disruption of the Deltapsim; and (iii)
      apoptosis. These results indicate that the enhancement of the generation of ROS
      and the disruption of Deltapsim are events involved in the apoptotic pathway of
      EC-109 induced by CDDP.

PMID- 17534410
TI  - Leptospirosis in farmed deer in New Zealand : a review.
AB  - Current knowledge of leptospirosis in farmed deer in New Zealand is reviewed.
      Over the past 25 years, leptospirosis has been reported to occur in individual
      cases as well as in herd outbreaks in farmed deer and in human cases linked to
      farmed deer. Serological studies and evidence from bacterial culture suggest
      infection is widespread. Mixing of young stock from several sources appears to be
      a significant risk factor for outbreaks. The culture of Leptospira interrogans
      serovars Hardjobovis, Pomona and Copenhageni has been reported. Infection with
      serovar Hardjobovis had the highest prevalence, either individually or mixed with
      serovar Pomona. Infection with serovar Copenhageni appears uncommon and its
      pathogenicity in deer is unproven. Titres to serovars Australis, Ballum,
      Balcanica and Tarassovi have been reported. Deer appear to be maintenance hosts
      for serovar Hardjobovis, incidental or accidental hosts and probably a
      maintenance population for serovar Pomona, since some infections persist for
      several months, and accidental hosts for serovar Copenhageni. Serovar Pomona
      appears to produce clinical and probably subclinical disease, whereas serovar
      Hardjobovis appears to cause only subclinical disease, although the relative risk
      of disease causation has not been determined. Clinical disease is usually
      manifested by haemolysis, jaundice, renal lesions, haemoglobinuria and often by
      sudden death. Renal lesions are commonly observed at slaughter and many are
      associated with leptospiral infections. Occupationally, slaughterhouse workers
      appear to be at greatest risk of contracting the disease from deer. Vaccination
      produces serological responses, but its effectiveness in protecting against
      disease, and prevention or reduction of shedding in urine, has not yet been
      confirmed in deer. More robust knowledge of the epidemiology of leptospiral
      infections in deer, and the effectiveness of vaccines and vaccination regimes, is
      needed to assist the deer industry to develop a strategy to manage this disease.

PMID- 17534411
TI  - Behavioural, biochemical, and pathological responses of possums (Trichosurus
      vulpecula) poisoned with phosphorus paste.
AB  - AIM: To investigate the behavioural, biochemical and pathological responses of
      possums following poisoning with phosphorus paste, in order to assess the
      implications for the welfare of possums. METHODS: After ingestion of phosphorus
      paste by wild-caught possums (18 high dose, nine low dose, and 12 non-poisoned
      controls), behavioural observations were made at 15-min intervals for 24 h or
      until death. Serum biochemistry, and gross and microscopic pathology were
      assessed at 3-hourly intervals in a further 21 possums. RESULTS: Possums that
      ingested phosphorus paste developed an abnormal posture (high incidence of
      crouching after 4-8 h), mild congestion of the gastric mucosa, and elevated
      levels of creatine kinase (CK) in serum after 3-6 h. Retching was observed in 67%
      possums, and 44% vomited at least once. Possums were prostrate from about 18 h
      after eating the poison, and the response to handling, an indicator of
      consciousness, was lost at about 24 h, followed by death at 25 h. CONCLUSION: The
      main welfare concern was the possibility of discomfort or pain caused by the
      congestion of the gastric mucosa, as indicated by the crouched posture adopted by
      poisoned possums. Retching and vomiting may also have caused pain and distress.
      The degree of pain or discomfort would depend on the degree of congestion of the
      gastric mucosa, which was typically mild, and on the duration and severity of
      retching and vomiting, which were typically short and mild. Possums remained
      conscious until 1 h before death, implying that they were able to experience pain
      and distress from the effects of ingestion of phosphorus for almost the entire
      period of illness, which lasted for approximately one day.

PMID- 17534412
TI  - Oestradiol and genistein reduce food intake in male and female overweight cats
      after gonadectomy.
AB  - AIM: To determine if exogenous oestradiol or the phyto-oestrogen genistein could
      reduce food intake in male and female cats fed ad libitum that had been allowed
      to accrue excessive bodyfat following neutering. METHODS: Sixteen adult (eight
      female, eight male) cats were neutered and allowed to increase their bodyweight
      (BW) through feeding ad libitum of a complete and balanced dry diet. Oestradiol
      was injected subcutaneously for 5-day periods in incremental doses (0.25-4 microg
      per cat), then food intake was recorded, and vaginal cytological changes were
      observed in females. Similarly, genistein was administered orally for 5-day
      periods in incremental doses (5-100 mg/kg). RESULTS: In males and females, both
      oestradiol (p<0.001) and genistein (p=0.037) significantly reduced food intake
      during treatment, and the minimum daily doses that produced a significant effect
      were 0.5 mug and 100 mg/kg, respectively. The minimum daily dose of oestradiol
      that produced a significant effect on food intake was not associated with changes
      in vaginal cytology over the 5-day treatment period. CONCLUSIONS AND CLINICAL
      RELEVANCE: Gonadal oestradiol appeared to be a key modulator of food intake in
      both male and female cats, and replacement of oestrogen to neutered cats via
      oestradiol or an oestrogen surrogate such as genistein has potential for reducing
      the prevalence of obesity in neutered cats.

PMID- 17534413
TI  - The effect of plain, eggbar and 6 degrees-wedge shoes on the distribution of
      pressure under the hoof of horses at the walk.
AB  - AIM: To quantify the effect of plain, wedged and eggbar shoes on the distribution
      of pressure under the hoof of horses at the walk, at selected areas of interest
      (AOI), to find scientific evidence for the perceived efficacy of these shoes in
      the treatment of palmar heel pain. METHODS: Six clinically sound adult Warmblood
      mares weighing 551 (SD 25) kg were shod (forelegs) with either plain, eggbar or 6
      degrees-wedge shoes using a latin-square experimental design. All horses were
      shod by the same farrier, and each balanced and aligned for its individual
      conformation. Data were collected on three walking strides for each foreleg using
      a 550 x 405-mm pressure plate to quantify the distribution of pressure under each
      type of shoe at five AOI. RESULTS: Landing of the hoof with all three shoes was
      predominantly from lateral to medial (range 7-15 msec). Irrespective of the type
      of shoe, the greatest pressure was found in the lateral and medial toe (lateral
      39.7 (SE 0.6) N/cm2 and medial 35.0 (SE 0.5) N/cm2) and the point of the toe
      (33.3 (SE 0.5) N/cm2). The lowest peak pressure was in the heel (lateral 25.9 (SE
      0.5) N/cm2 and medial 21.1 (SE 0.4) N/cm2; p<0.05). Eggbar and wedge shoes
      increased total stance time (938 (SE 8) msec and 952 (SE 6) msec, respectively)
      compared with plain shoes (898 (SE 14) msec) (p<0.05). The wedge shoe reduced
      breakover compared with the plain and eggbar shoes (13.8% vs 15.8% and 14.5%,
      respectively; p<0.05). The eggbar shoe had lower total shoe peak pressure (29.5
      (SE 0.7) N/cm2) than plain (31.8 (SE 0.5) N/cm2) and wedge (30.9 (SE 0.6) N/cm2)
      shoes. CONCLUSIONS AND CLINICAL RELEVANCE: Both the eggbar and 6 degrees-wedge
      shoe offer advantages for palmar heel pain. In comparison to the plain shoe, the
      eggbar shoe had less peak pressure at the heel AOI, and across the entire shoe,
      due to the greater bearing surface and the effect of the longer heel. The 6
      degrees-wedge shoe had greater loading on the lateral heel AOI, but promoted
      earlier breakover at the toe. Both shoes offer advantages for the horse with
      palmar heel pain, though choice of shoe will depend on clear identification of
      the causative factors, to provide therapeutic shoeing that maximises the
      individual horse's response.

PMID- 17534414
TI  - Epididymal and testicular lesions in rams following experimental infection with
      Actinobacillus seminis.
AB  - AIM: To investigate and assess the epididymal and testicular lesions in rams up
      to 44 days after inoculation with Actinobacillus seminis via various routes.
      METHODS: Forty-four young (18-24 months old) rams were randomly divided into nine
      test and two control groups (n=4 per group). The test rams were infected by
      installation, drenching or injection of A. seminis organisms cultured for 24 h in
      a brain-heart infusion (BHI) broth containing 2.3 x 10(9) cells/ml, via the
      following nine routes: intra-epididymal (1 ml), intravenous (3 ml), intra
      urethral (3 ml), intra-preputial (3 ml), vas deferens (1 ml), intramuscular (3
      ml), oral (10 ml), intranasal (3 ml), and intra-conjunctival (3 drops). All test
      rams were necropsied 9-44 days post-inoculation (p.i.). Control rams were
      subdivided into in-contact and non-contact groups and necropsied at 45 and 46
      days p.i., respectively. Thin tissue sections were examined for histopathology.
      RESULTS: Gross lesions were evident only in rams inoculated intra-epididymally.
      Epididymides on the inoculated side were two to three times larger than those on
      the un-inoculated side, and the testes attached to the inoculated epididymides
      were also enlarged. Fibrinopurulent periorchitis and tunica vaginalitis were seen
      in three rams and atrophy in one. Microscopically, epididymitis was present in 17
      (47%) rams, the highest incidence being in the cauda, followed by the caput and
      the corpus epididymis. Seminiferous tubular degeneration with areas of
      lymphocytic infiltration were seen in four rams: three inoculated via the cauda
      epididymis and one via the urethra. No epididymal and/or testicular lesions were
      seen in rams inoculated via the nasal and conjunctival routes. CONCLUSIONS:
      Injection of A. seminis in young rams by all routes except intra-conjunctival and
      intranasal resulted in epididymitis, predominantly in the cauda epididymis.
      Development of lesions in the reproductive tract following non-genital routes of
      inoculation supports earlier suggestions that non-venereal transmission of
      genital actinobacillosis occurs. This study confirmed the predilection of A.
      seminis for the epididymis, especially the cauda.

PMID- 17534415
TI  - Thysanoptera infestation on skin and periorbital cellulitis in ostriches
      (Struthio camelus) aged 14 months.
AB  - AIM: To report the infestation of Thysanoptera (Limothrips denticornis) on
      ostriches (Struthio camelus) and to determine their relative density. METHODS: A
      farm in Poland was studied on which ostriches aged 14 months were severely
      infested with L. denticornis (thrips). Thrips were collected and their density on
      the neck, torso and legs (10 cm2) of 85 ostriches determined at 0600, 1200 and
      1800 h, respectively, over 7 days. At the same times, apparent densities of
      thrips/m2 were determined in adjacent grassy areas (120 m2) on a muslin cloth
      impregnated with permethrin. Thrips were mounted onto slides in Hoyer's medium,
      for identification. RESULTS: The apparent density of thrips was greatest at 1200
      h, and was greater on the neck than the torso and legs (p=0.03). In adjacent
      surroundings, densities were also highest at 1200 h (mean 199 (SE 9.3) thrips/m2)
      and were similar to the maximum densities recorded on the necks of ostriches at
      that time (mean 205 (SE 6.4) thrips/m2). Ostriches engaged in excessive preening
      and attempted to scratch their head/neck with their feet. Numerous small, pale
      red papules were observed on the skin. Observations of periorbital cellulitis,
      conjunctivitis, blepharitis, watery discharge, inflammation, and sclerotic
      discolouration were noted in 65 ostriches. CONCLUSION: Observations were
      commensurate with L. denticornis infestation. CLINICAL RELEVANCE: Infestation may
      exacerbate stress levels and subsequently lead to a reduction in feed intake and
      performance. The infestation and subsequent irritation from thrips impacts
      negatively on the general health of ostriches by damaging skin and irritating
      eyes.

PMID- 17534416
TI  - Failure to detect Salmonella species in a population of wild tuatara (Sphenodon
      punctatus).
AB  - AIM: To assess the prevalence of faecal excretion of Salmonella serovars by wild
      tuatara (Sphenodon punctatus) on Stephens Island, New Zealand. METHODS: One
      hundred cloacal swabs obtained as part of health-screening for the translocation
      of adult tuatara from Stephens Island were subjected to general aerobic culture
      and enrichment, and cultured specifically for Salmonella spp. RESULTS: No
      Salmonella spp were cultured from any of the cloacal samples, which suggests
      that, at the 95% confidence interval, the maximum prevalence of tuatara in the
      island population that were shedding Salmonella spp not detected by our sample
      size was 1.5%. Mixed bacteria were grown from the 70 cloacal swabs cultured
      aerobically. A predominant organism was evident in 30 cultures, and these were
      identified as Hafnia alvei type 1 (n=16) and type 2 (n=7), Corynebacterium spp
      (n=4), Klebsiella oxytoca (n=2), and Moraxella spp (n=1). CONCLUSIONS: The
      absence of intestinal carriage of Salmonella spp by the tuatara sampled in this
      study may indicate either lack of exposure, or an innate resistance to intestinal
      colonisation in tuatara. The significance of the other bacteria cultured as
      potential pathogens to the tuatara and as zoonotic risks is also uncertain.
      Wildlife managers should screen translocated reptiles for Salmonella spp, and
      thereby avoid exposing wild and managed populations to infection.

PMID- 17534417
TI  - An outbreak of rickets in Corriedale sheep: evidence for a genetic aetiology.
AB  - CASE HISTORY: A skeletal disease characterised by lameness, limb deformities and
      reduced growth rate occurred over two successive years in lambs born on a
      commercial sheep farm in Marlborough. A genetic aetiology was considered likely
      following exclusion of other known causes of rickets and because of the
      progressive nature of the disease, even after affected animals were transferred
      to another property. CLINICAL FINDINGS: Affected lambs appeared normal at birth
      but developed clinical signs during the first 2 months of life. The most severely
      affected animals either died or were euthanised within the first year of life,
      but some survived to breeding age. Serum biochemistry revealed hypocalcaemia,
      hypophosphataemia and increased concentrations of 1,25 dihydroxyvitamin D. The
      mean serum 25 hydroxyvitamin D concentration was similar to that of control
      lambs. PATHOLOGICAL FINDINGS: Gross lesions included enlarged costochondral
      junctions, bilateral irregularity of articular surfaces on humeral heads due to
      collapse of subchondral bone, thickened cortices in long bones and irregular
      thickening of physeal cartilages. Microscopically, tongues of hypertrophic
      chondrocytes extended from physes into metaphyseal regions; metaphyseal
      trabeculae were thick, disorganised and often lined by wide osteoid seams.
      Osteoclastic activity was excessive both in cortical and trabecular bone.
      DIAGNOSIS: Inherited rickets in Corriedale sheep. CLINICAL RELEVANCE AND
      CONCLUSIONS: This disease is likely to be present in several Corriedale sheep
      flocks in New Zealand and may have been misdiagnosed as arthritis or other
      diseases causing lameness and/or poor growth. A defect in end-organ
      responsiveness to 1,25 dihydroxyvitamin D is the likely mechanism. This disease
      of sheep may be a useful model for studying vitamin D metabolism and the
      treatment of inherited forms of rickets in human beings.

PMID- 17534418
TI  - Combined xeno/auto-grafting of a benign osteolytic lesion in a dog, using a novel
      bovine cancellous bone biomaterial.
AB  - CASE HISTORY: A 4-year-old female Labrador Retriever was diagnosed with an
      osteolytic lesion of the right distal radius. CLINICAL FINDINGS: Radiographs
      indicated a well-circumscribed radiolucent area 18 x 15 x 8 mm, centred on the
      distal radial physeal scar. DIAGNOSIS: Histopathology, performed via Jamshidi
      needle biopsy and following surgical curettage, was inconclusive but suggested
      either an aneurysmal bone cyst or fibrous dysplasia. CLINICAL RELEVANCE: A novel
      processed cancellous bovine bone xenograft was used in conjunction with
      autogenous cancellous bone (at a ratio of approximately 4:1) to fill the curetted
      defect. There were no observed complications associated with the use of this new
      biomaterial. Osteointegration of the bone graft was followed using conventional
      radiographs and peripheral quantitative computed tomography (pQCT) for 10 months
      post-operatively. Radiographically, the osteolytic lesion modelled to resemble
      metaphyseal trabeculation. The cross-sectional area and the average bone density
      of the grafted lesion determined using pQCT data increased over time, suggesting
      healthy osteoconduction and native bone production.

PMID- 17534419
TI  - Death by chocolate: a fatal problem for an inquisitive wild parrot.
AB  - CASE HISTORY: An adult male kea (Nestor notabilis) in good body condition was
      found dead at Aoraki/Mt Cook Village, in the Southern Alps of New Zealand. The
      bird had previously been involved in behavioural tests of problem-solving
      ability. CLINICAL AND PATHOLOGICAL FINDINGS: The bird had substantial
      subcutaneous and abdominal reserves of fat. The crop contained 20 g of what
      appeared to be dark chocolate; a conservative estimate of the dose of
      methylxanthines ingested by the bird was 250 mg/kg theobromine, 20 mg/kg caffeine
      and 3 mg/kg theophylline. Histopathological examination revealed acute
      degenerative changes to hepatocytes, renal tubules, and cerebrocortical neurons.
      DIAGNOSIS: Acute combination methylxanthine toxicity after opportunistic
      ingestion of chocolate. CLINICAL RELEVANCE: This is the first report of the
      pathological findings of methylxanthine toxicity in a wild parrot, and
      illustrates the need to ensure that kea are protected from the toxic by-products
      of human habitation, and the difficulties in ensuring this against a neophilic,
      inquisitive and innovative parrot.

PMID- 17534420
TI  - Expanded transposition flap technique for total and subtotal resurfacing of the
      face and neck.
AB  - BACKGROUND: The reconstruction of major burn and other deformities resulting from
      significant soft tissue deficits of the face and neck is a continuing challenge
      for surgeons who wish to reliably restore facial function and aesthetic
      appearance. A primary problem is deficiency of well-matched donor skin. Other
      problems include the unique characteristics of facial skin, the fine anatomic
      nuances, and the unique functional demands placed on the face. This article
      describes an expanded shoulder transposition flap that can provide a large amount
      of both flap and full-thickness skin graft for total and subtotal reconstruction
      of the face. METHODS: An expanded shoulder transposition flap has been used since
      1986 for head and neck resurfacing 58 times in 41 patients ranging in age from 2
      to 62 years. The details of the technique and the results of the flap including
      complications are described. RESULTS: The flap proved remarkably reliable and
      reproducible in resurfacing the peripheral facial aesthetic units. The pedicle
      skin is often used for grafting of the central face with its finer features. The
      donor site of the flap is closed primarily. CONCLUSIONS: Twenty years' experience
      with expanded transposition flaps has shown it to be reliable and versatile in
      the reconstruction of major soft tissue deficits of the face and neck. It is a
      technique that provides economy of tissue, versatility, and is well within the
      skill, patience, and courage of most reconstructive surgeons.

PMID- 17534421
TI  - Regulation of plant developmental processes by a novel splicing factor.
AB  - Serine/arginine-rich (SR) proteins play important roles in constitutive and
      alternative splicing and other aspects of mRNA metabolism. We have previously
      isolated a unique plant SR protein (SR45) with atypical domain organization.
      However, the biological and molecular functions of this novel SR protein are not
      known. Here, we report biological and molecular functions of this protein. Using
      an in vitro splicing complementation assay, we showed that SR45 functions as an
      essential splicing factor. Furthermore, the alternative splicing pattern of
      transcripts of several other SR genes was altered in a mutant, sr45-1, suggesting
      that the observed phenotypic abnormalities in sr45-1 are likely due to altered
      levels of SR protein isoforms, which in turn modulate splicing of other pre
      mRNAs. sr45-1 exhibited developmental abnormalities, including delayed flowering,
      narrow leaves and altered number of petals and stamens. The late flowering
      phenotype was observed under both long days and short days and was rescued by
      vernalization. FLC, a key flowering repressor, is up-regulated in sr45-1
      demonstrating that SR45 influences the autonomous flowering pathway. Changes in
      the alternative splicing of SR genes and the phenotypic defects in the mutant
      were rescued by SR45 cDNA, further confirming that the observed defects in the
      mutant are due to the lack of SR45. These results indicate that SR45 is a novel
      plant-specific splicing factor that plays a crucial role in regulating
      developmental processes.

PMID- 17534422
TI  - Short RNA guides cleavage by eukaryotic RNase III.
AB  - In eukaryotes, short RNAs guide a variety of enzymatic activities that range from
      RNA editing to translation repression. It is hypothesized that pre-existing
      proteins evolved to bind and use guide RNA during evolution. However, the
      capacity of modern proteins to adopt new RNA guides has never been demonstrated.
      Here we show that Rnt1p, the yeast orthologue of the bacterial dsRNA-specific
      RNase III, can bind short RNA transcripts and use them as guides for sequence
      specific cleavage. Target cleavage occurred at a constant distance from the Rnt1p
      binding site, leaving the guide RNA intact for subsequent cleavage. Our results
      indicate that RNase III may trigger sequence-specific RNA degradation independent
      of the RNAi machinery, and they open the road for a new generation of precise RNA
      silencing tools that do not trigger a dsRNA-mediated immune response.

PMID- 17534423
TI  - Endothelial cells' activation and apoptosis induced by a subset of antibodies
      against human cytomegalovirus: relevance to the pathogenesis of atherosclerosis.
AB  - BACKGROUND: Human cytomegalovirus (hCMV) is involved in the pathogenesis of
      atherosclerosis. We have previously shown in patients with atherosclerosis that
      antibodies directed against the hCMV-derived proteins US28 and UL122 are able to
      induce endothelial cell damage and apoptosis of non-stressed endothelial cells
      through cross-rection with normally expressed surface molecules. Our aim was to
      dissect the molecular basis of such interaction and to investigate mechanisms
      linking innate immunity to atherosclerosis. METHODOLOGY/PRINCIPAL FINDINGS: We
      analysed the gene expression profiles in endothelial cells stimulated with
      antibodies affinity-purified against either the UL122 or the US28 peptides using
      the microarray technology. Microarray results were validated by quantitative PCR
      and by detection of proteins in the medium. Supernatant of endothelial cells
      incubated with antibodies was analysed also for the presence of Heat Shock
      Protein (HSP)60 and was used to assess stimulation of Toll-Like Receptor-4
      (TLR4). Antibodies against UL122 and US28 induced the expression of genes
      encoding for adhesion molecules, chemokines, growth factors and molecules
      involved in the apoptotis process together with other genes known to be involved
      in the initiation and progression of the atherosclerotic process. HSP60 was
      released in the medium of cells incubated with anti-US28 antibodies and was able
      to engage TLR4. CONCLUSIONS/SIGNIFICANCE: Antibodies directed against hCMV
      modulate the expression of genes coding for molecules involved in activation and
      apoptosis of endothelial cells, processes known to play a pivotal role in the
      pathogenesis of atherosclerosis. Moreover, endothelial cells exposed to such
      antibodies express HSP60 on the cell surface and release HSP60 in the medium able
      to activate TLR4. These data confirm that antibodies directed against hCMV
      derived proteins US28 and UL122 purified from patients with coronary artery
      disease induce endothelial cell damage and support the hypothesis that hCMV
      infection may play a crucial role in mediating the atherosclerotic process.

PMID- 17534424
TI  - Human ClC-6 is a late endosomal glycoprotein that associates with detergent
      resistant lipid domains.
AB  - BACKGROUND: The mammalian CLC protein family comprises nine members (ClC-1 to -7
      and ClC-Ka, -Kb) that function either as plasma membrane chloride channels or as
      intracellular chloride/proton antiporters, and that sustain a broad spectrum of
      cellular processes, such as membrane excitability, transepithelial transport,
      endocytosis and lysosomal degradation. In this study we focus on human ClC-6,
      which is structurally most related to the late endosomal/lysomal ClC-7. PRINCIPAL
      FINDINGS: Using a polyclonal affinity-purified antibody directed against a unique
      epitope in the ClC-6 COOH-terminal tail, we show that human ClC-6, when
      transfected in COS-1 cells, is N-glycosylated in a region that is evolutionary
      poorly conserved between mammalian CLC proteins and that is located between the
      predicted helices K and M. Three asparagine residues (N410, N422 and N432) have
      been defined by mutagenesis as acceptor sites for N-glycosylation, but only two
      of the three sites seem to be simultaneously N-glycosylated. In a differentiated
      human neuroblastoma cell line (SH-SY5Y), endogenous ClC-6 colocalizes with LAMP
      1, a late endosomal/lysosomal marker, but not with early/recycling endosomal
      markers such as EEA-1 and transferrin receptor. In contrast, when transiently
      expressed in COS-1 or HeLa cells, human ClC-6 mainly overlaps with markers for
      early/recycling endosomes (transferrin receptor, EEA-1, Rab5, Rab4) and not with
      late endosomal/lysosomal markers (LAMP-1, Rab7). Analogously, overexpression of
      human ClC-6 in SH-SY5Y cells also leads to an early/recycling endosomal
      localization of the exogenously expressed ClC-6 protein. Finally, in transiently
      transfected COS-1 cells, ClC-6 copurifies with detergent-resistant membrane
      fractions, suggesting its partitioning in lipid rafts. Mutating a juxtamembrane
      string of basic amino acids (amino acids 71-75: KKGRR) disturbs the association
      with detergent-resistant membrane fractions and also affects the segregation of
      ClC-6 and ClC-7 when cotransfected in COS-1 cells. CONCLUSIONS: We conclude that
      human ClC-6 is an endosomal glycoprotein that partitions in detergent resistant
      lipid domains. The differential sorting of endogenous (late endosomal) versus
      overexpressed (early and recycling endosomal) ClC-6 is reminiscent of that of
      other late endosomal/lysosomal membrane proteins (e.g. LIMP II), and is
      consistent with a rate-limiting sorting step for ClC-6 between early endosomes
      and its final destination in late endosomes.

PMID- 17534425
TI  - Insulin-like growth factor 1 (IGF-1) mediates the effects of enriched environment
      (EE) on visual cortical development.
AB  - Enriched environment (EE) has been recently shown to affect visual cortex
      development and plasticity, and to prevent dark rearing effects. The factors
      mediating EE effects on visual cortical development and plasticity are still
      unclear. We have investigated whether IGF-1 is involved in mediating EE effects
      on the developing visual cortex. We show that EE increases the number of IGF-1
      positive neurons in the visual cortex at P18. Increasing IGF-1 in the visual
      cortex of non-EE rats by means of osmotic minipumps implanted at P18 mimics EE
      effects, accelerating visual acuity development, assessed with Visual Evoked
      Potentials (VEPs). Blocking IGF-1 action in the visual cortex of EE rats by means
      of the IGF-1 receptor antagonist JB1 from P18 completely blocks EE action on
      visual acuity development. These results show that IGF-1 is a key factor
      mediating EE effects on visual cortical development. We then show that IGF-1
      affects GAD65 immunoreactivity in perisomatic innervation and the condensation of
      Chondroitin Sulphate Proteoglycans (CSPGs) in perineuronal nets (PNNs) in the
      visual cortex. This suggests that IGF-1 action in mediating EE effects could be
      exerted through the modulation of intracortical inhibitory circuitry and PNN
      development.

PMID- 17534426
TI  - Suffix-specific RNAi leads to silencing of F element in Drosophila melanogaster.
AB  - Separate conserved copies of suffix, a short interspersed Drosophila retroelement
      (SINE), and also divergent copies in the 3' untranslated regions of the three
      genes, have already been described. Suffix has also been identified on the 3' end
      of the Drosophila non-LTR F element, where it forms the last conserved domain of
      the reverse transcriptase (RT). In our current study, we show that the separate
      copies of suffix are far more actively transcribed than their counterparts on the
      F element. Transcripts from both strands of suffix are present in RNA
      preparations during all stages of Drosophila development, providing the potential
      for the formation of double-stranded RNA and the initiation of RNA interference
      (RNAi). Using in situ RNA hybridization analysis, we have detected the expression
      of both sense and antisense suffix transcripts in germinal cells. These sense and
      antisense transcripts are colocalized in the primary spermatocytes and in the
      cytoplasm of the nurse cells, suggesting that they form double-stranded RNA. We
      performed further analyses of suffix-specific small RNAs using northern blotting
      and SI nuclease protection assays. Among the total RNA preparations isolated from
      embryos, larvae, pupae and flies, suffix-specific small interfering RNAs (siRNAs)
      were detected only in pupae. In wild type ovaries, both the siRNAs and longer
      suffix-specific Piwi-interacting RNAs (piRNAs) were observed, whereas in ovaries
      of the Dicer-2 mutant, only piRNAs were detected. We further found by 3' RACE
      that in pupae and ovaries, F element transcripts lacking the suffix sequence are
      also present. Our data provide direct evidence that suffix-specific RNAi leads to
      the silencing of the relative LINE (long interspersed element), F element, and
      suggests that SINE-specific RNA interference could potentially downregulate a set
      of genes possessing SINE stretches in their 5' or 3' non-coding regions. These
      data also suggest that double stranded RNAs possessing suffix are processed by
      both RNAi and an additional silencing mechanism.

PMID- 17534427
TI  - A novel DBL-domain of the P. falciparum 332 molecule possibly involved in
      erythrocyte adhesion.
AB  - Plasmodium falciparum malaria is brought about by the asexual stages of the
      parasite residing in human red blood cells (RBC). Contact between the erythrocyte
      surface and the merozoite is the first step for successful invasion and
      proliferation of the parasite. A number of different pathways utilised by the
      parasite to adhere and invade the host RBC have been characterized, but the
      complete biology of this process remains elusive. We here report the
      identification of an open reading frame (ORF) representing a hitherto unknown
      second exon of the Pf332 gene that encodes a cysteine-rich polypeptide with a
      high degree of similarity to the Duffy-binding-like (DBL) domain of the
      erythrocyte-binding-ligand (EBL) family. The sequence of this DBL-domain is
      conserved and expressed in all parasite clones/strains investigated. In addition,
      the expression level of Pf332 correlates with proliferation efficiency of the
      parasites in vitro. Antibodies raised against the DBL-domain are able to reduce
      the invasion efficiency of different parasite clones/strains. Analysis of the DBL
      domain revealed its ability to bind to uninfected human RBC, and moreover
      demonstrated association with the iRBC surface. Thus, Pf332 is a molecule with a
      potential role to support merozoite invasion. Due to the high level of
      conservation in sequence, the novel DBL-domain of Pf332 is of possible importance
      for development of novel anti-malaria drugs and vaccines.

PMID- 17534429
TI  - Tuning curvature and stability of monoolein bilayers by designer lipid-like
      peptide surfactants.
AB  - This study reports the effect of loading four different charged designer lipid
      like short anionic and cationic peptide surfactants on the fully hydrated
      monoolein (MO)-based Pn3m phase (Q(224)). The studied peptide surfactants
      comprise seven amino acid residues, namely A(6)D, DA(6), A(6)K, and KA(6). D
      (aspartic acid) bears two negative charges, K (lysine) bears one positive charge,
      and A (alanine) constitutes the hydrophobic tail. To elucidate the impact of
      these peptide surfactants, the ternary MO/peptide/water system has been
      investigated using small-angle X-ray scattering (SAXS), within a certain range of
      peptide concentrations (R<or=0.2) and temperatures (25 to 70 degrees C). We
      demonstrate that the bilayer curvature and the stability are modulated by: i) the
      peptide/lipid molar ratio, ii) the peptide molecular structure (the degree of
      hydrophobicity, the type of the hydrophilic amino acid, and the headgroup
      location), and iii) the temperature. The anionic peptide surfactants, A(6)D and
      DA(6), exhibit the strongest surface activity. At low peptide concentrations (R =
      0.01), the Pn3m structure is still preserved, but its lattice increases due to
      the strong electrostatic repulsion between the negatively charged peptide
      molecules, which are incorporated into the interface. This means that the anionic
      peptides have the effect of enlarging the water channels and thus they serve to
      enhance the accommodation of positively charged water-soluble active molecules in
      the Pn3m phase. At higher peptide concentration (R = 0.10), the lipid bilayers
      are destabilized and the structural transition from the Pn3m to the inverted
      hexagonal phase (H(2)) is induced. For the cationic peptides, our study
      illustrates how even minor modifications, such as changing the location of the
      headgroup (A(6)K vs. KA(6)), affects significantly the peptide's effectiveness.
      Only KA(6) displays a propensity to promote the formation of H(2), which suggests
      that KA(6) molecules have a higher degree of incorporation in the interface than
      those of A(6)K.

PMID- 17534428
TI  - Molecular analysis of core kinetochore composition and assembly in Drosophila
      melanogaster.
AB  - BACKGROUND: Kinetochores are large multiprotein complexes indispensable for
      proper chromosome segregation. Although Drosophila is a classical model organism
      for studies of chromosome segregation, little is known about the organization of
      its kinetochores. METHODOLOGY/PRINCIPAL FINDINGS: We employed bioinformatics,
      proteomics and cell biology methods to identify and analyze the interaction
      network of Drosophila kinetochore proteins. We have shown that three Drosophila
      proteins highly diverged from human and yeast Ndc80, Nuf2 and Mis12 are indeed
      their orthologues. Affinity purification of these proteins from cultured
      Drosophila cells identified a further five interacting proteins with weak
      similarity to subunits of the SPC105/KNL-1, MIND/MIS12 and NDC80 kinetochore
      complexes together with known kinetochore associated proteins such as
      dynein/dynactin, spindle assembly checkpoint components and heterochromatin
      proteins. All eight kinetochore complex proteins were present at the kinetochore
      during mitosis and MIND/MIS12 complex proteins were also centromeric during
      interphase. Their down-regulation led to dramatic defects in chromosome
      congression/segregation frequently accompanied by mitotic spindle elongation. The
      systematic depletion of each individual protein allowed us to establish
      dependency relationships for their recruitment onto the kinetochore. This
      revealed the sequential recruitment of individual members of first, the
      MIND/MIS12 and then, NDC80 complex. CONCLUSIONS/SIGNIFICANCE: The Drosophila
      MIND/MIS12 and NDC80 complexes and the Spc105 protein, like their counterparts
      from other eukaryotic species, are essential for chromosome congression and
      segregation, but are highly diverged in sequence. Hierarchical dependence
      relationships of individual proteins regulate the assembly of Drosophila
      kinetochore complexes in a manner similar, but not identical, to other organisms.

PMID- 17534430
TI  - Association between the ACCN1 gene and multiple sclerosis in Central East
      Sardinia.
AB  - Multiple genome screens have been performed to identify regions in linkage or
      association with Multiple Sclerosis (MS, OMIM 126200), but little overlap has
      been found among them. This may be, in part, due to a low statistical power to
      detect small genetic effects and to genetic heterogeneity within and among the
      studied populations. Motivated by these considerations, we studied a very special
      population, namely that of Nuoro, Sardinia, Italy. This is an isolated, old, and
      genetically homogeneous population with high prevalence of MS. Our study sample
      includes both nuclear families and unrelated cases and controls. A multi-stage
      study design was adopted. In the first stage, microsatellites were typed in the
      17q11.2 region, previously independently found to be in linkage with MS. One
      significant association was found at microsatellite D17S798. Next, a
      bioinformatic screening of the region surrounding this marker highlighted an
      interesting candidate MS susceptibility gene: the Amiloride-sensitive Cation
      Channel Neuronal 1 (ACCN1) gene. In the second stage of the study, we resequenced
      the exons and the 3' untranslated (UTR) region of ACCN1, and investigated the MS
      association of Single Nucleotide Polymorphisms (SNPs) identified in that region.
      For this purpose, we developed a method of analysis where complete, phase-solved,
      posterior-weighted haplotype assignments are imputed for each study individual
      from incomplete, multi-locus, genotyping data. The imputed assignments provide an
      input to a number of proposed procedures for testing association at a
      microsatellite level or of a sequence of SNPs. These include a Mantel-Haenszel
      type test based on expected frequencies of pseudocase/pseudocontrol haplotypes,
      as well as permutation based tests, including a combination of permutation and
      weighted logistic regression analysis. Application of these methods allowed us to
      find a significant association between MS and the SNP rs28936 located in the 3'
      UTR segment of ACCN1 with p = 0.0004 (p = 0.002, after adjusting for multiple
      testing). This result is in tune with several recent experimental findings which
      suggest that ACCN1 may play an important role in the pathogenesis of MS.

PMID- 17534431
TI  - Hormone-mediated gene regulation and bioinformatics: learning one from the other.
AB  - The ability to manage the constantly growing clinically relevant information in
      genetics available on the internet is becoming crucial in medical practice.
      Therefore, training students in teaching environments that develop bioinformatics
      skills is a particular challenge to medical schools. We present here an
      instructional approach that potentiates learning of hormone/vitamin mechanisms of
      action in gene regulation with the acquisition and practice of bioinformatics
      skills. The activity is integrated within the study of the Endocrine System
      module. Given a nucleotide sequence of a hormone or vitamin-response element,
      students use internet databases and tools to find the gene to which it belongs.
      Subsequently, students search how the corresponding hormone/vitamin influences
      the expression of that particular gene and how a dysfunctional interaction might
      cause disease. This activity was presented for four consecutive years to cohorts
      of 50-60 students/year enrolled in the 2(nd) year of the medical degree. 90% of
      the students developed a better understanding of the usefulness of bioinformatics
      and 98% intend to use web-based resources in the future. Since hormones and
      vitamins regulate genes of all body organ systems, this activity successfully
      integrates the whole body physiology of the medical curriculum.

PMID- 17534432
TI  - Accelerated variant of idiopathic pulmonary fibrosis: clinical behavior and gene
      expression pattern.
AB  - BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is characterized by the insidious
      onset of dyspnea or cough. However, a subset of patients has a short duration of
      symptoms with rapid progression to end-stage disease. In this study, we evaluated
      clinical and molecular features of "rapid" and "slow" progressors with IPF.
      METHODS AND FINDINGS: 26 patients with <6 months of symptoms before first
      presentation [rapid progressors] and 88 patients with >24 months of symptoms
      [slow progressors] were studied. Survival was analyzed by the Kaplan-Meyer method
      and proportional hazard's model. Lung microarrays and tissue proteins were
      measured in a subset of patients. No differences were found in age, physiologic
      impairment and bronchoalveolar lavage (BAL) cellular profile. There were more
      males (OR = 6.5; CI:1.4-29.5; p = 0.006) and smokers (OR = 3.04; CI:1.1-8.3; p =
      0.04) in the rapid progressors group. Survival from the beginning of symptoms was
      significantly reduced in rapid progressors (HR = 9.0; CI:4.48-18.3; p<0.0001) and
      there was a tendency for decreased survival from the time of diagnosis (HR = 1.5;
      CI:0.81-2.87; p = 0.18). We identified 437 differentially expressed genes. Lungs
      of rapid progressors overexpressed genes involved in morphogenesis, oxidative
      stress, migration/proliferation, and genes from fibroblasts/smooth muscle cells.
      Upregulation of two of these genes, adenosine-2B receptor and prominin-1/CD133,
      was validated by immunohistochemistry and were expressed by alveolar epithelial
      cells. BAL from rapid progressors showed a >2-fold increase of active matrix
      metalloproteinase-9, and induced a higher fibroblast migration compared with slow
      progressors and controls [238+/-98% versus 123+/-29% (p<0.05) and 30+/-17%
      (p<0.01)]. CONCLUSIONS/SIGNIFICANCE: A subgroup of IPF patients, predominantly
      smoking males, display an accelerated clinical course and have a gene expression
      pattern that is different from those with slower progression and longer survival.
      These findings highlight the variability in the progression of IPF, and may
      explain, in part, the difficulty in obtaining significant and reproducible
      results in studies of therapeutic interventions in patients with IPF.

PMID- 17534433
TI  - Melanoma screening with cellular phones.
AB  - BACKGROUND: Mobile teledermatology has recently been shown to be suitable for
      teledermatology despite limitations in image definition in preliminary studies.
      The unique aspect of mobile teledermatology is that this system represents a
      filtering or triage system, allowing a sensitive approach for the management of
      patients with emergent skin diseases. METHODOLOGY/PRINCIPAL FINDINGS: In this
      study we investigated the feasibility of teleconsultation using a new generation
      of cellular phones in pigmented skin lesions. 18 patients were selected
      consecutively in the Pigmented Skin Lesions Clinic of the Department of
      Dermatology, Medical University of Graz, Graz (Austria). Clinical and dermoscopic
      images were acquired using a Sony Ericsson with a built-in two-megapixel camera.
      Two teleconsultants reviewed the images on a specific web application
      (http://www.dermahandy.net/default.asp) where images had been uploaded in JPEG
      format. Compared to the face-to-face diagnoses, the two teleconsultants obtained
      a score of correct telediagnoses of 89% and of 91.5% reporting the clinical and
      dermoscopic images, respectively. CONCLUSIONS/SIGNIFICANCE: The present work is
      the first study performing mobile teledermoscopy using cellular phones. Mobile
      teledermatology has the potential to become an easy applicable tool for everyone
      and a new approach for enhanced self-monitoring for skin cancer screening in the
      spirit of the eHealth program of the European Commission Information for Society
      and Media.

PMID- 17534434
TI  - Whole-genome sequencing and assembly with high-throughput, short-read
      technologies.
AB  - While recently developed short-read sequencing technologies may dramatically
      reduce the sequencing cost and eventually achieve the $1000 goal for re
      sequencing, their limitations prevent the de novo sequencing of eukaryotic
      genomes with the standard shotgun sequencing protocol. We present SHRAP (SHort
      Read Assembly Protocol), a sequencing protocol and assembly methodology that
      utilizes high-throughput short-read technologies. We describe a variation on
      hierarchical sequencing with two crucial differences: (1) we select a clone
      library from the genome randomly rather than as a tiling path and (2) we sample
      clones from the genome at high coverage and reads from the clones at low
      coverage. We assume that 200 bp read lengths with a 1% error rate and inexpensive
      random fragment cloning on whole mammalian genomes is feasible. Our assembly
      methodology is based on first ordering the clones and subsequently performing
      read assembly in three stages: (1) local assemblies of regions significantly
      smaller than a clone size, (2) clone-sized assemblies of the results of stage 1,
      and (3) chromosome-sized assemblies. By aggressively localizing the assembly
      problem during the first stage, our method succeeds in assembling short, unpaired
      reads sampled from repetitive genomes. We tested our assembler using simulated
      reads from D. melanogaster and human chromosomes 1, 11, and 21, and produced
      assemblies with large sets of contiguous sequence and a misassembly rate
      comparable to other draft assemblies. Tested on D. melanogaster and the entire
      human genome, our clone-ordering method produces accurate maps, thereby
      localizing fragment assembly and enabling the parallelization of the subsequent
      steps of our pipeline. Thus, we have demonstrated that truly inexpensive de novo
      sequencing of mammalian genomes will soon be possible with high-throughput, short
      read technologies using our methodology.

PMID- 17534435
TI  - Regular patterns in cerebellar Purkinje cell simple spike trains.
AB  - BACKGROUND: Cerebellar Purkinje cells (PC) in vivo are commonly reported to
      generate irregular spike trains, documented by high coefficients of variation of
      interspike-intervals (ISI). In strong contrast, they fire very regularly in the
      in vitro slice preparation. We studied the nature of this difference in firing
      properties by focusing on short-term variability and its dependence on behavioral
      state. METHODOLOGY/PRINCIPAL FINDINGS: Using an analysis based on CV(2) values,
      we could isolate precise regular spiking patterns, lasting up to hundreds of
      milliseconds, in PC simple spike trains recorded in both anesthetized and awake
      rodents. Regular spike patterns, defined by low variability of successive ISIs,
      comprised over half of the spikes, showed a wide range of mean ISIs, and were
      affected by behavioral state and tactile stimulation. Interestingly, regular
      patterns often coincided in nearby Purkinje cells without precise synchronization
      of individual spikes. Regular patterns exclusively appeared during the up state
      of the PC membrane potential, while single ISIs occurred both during up and down
      states. Possible functional consequences of regular spike patterns were
      investigated by modeling the synaptic conductance in neurons of the deep
      cerebellar nuclei (DCN). Simulations showed that these regular patterns caused
      epochs of relatively constant synaptic conductance in DCN neurons.
      CONCLUSIONS/SIGNIFICANCE: Our findings indicate that the apparent irregularity in
      cerebellar PC simple spike trains in vivo is most likely caused by mixing of
      different regular spike patterns, separated by single long intervals, over time.
      We propose that PCs may signal information, at least in part, in regular spike
      patterns to downstream DCN neurons.

PMID- 17534436
TI  - Early trauma and increased risk for physical aggression during adulthood: the
      moderating role of MAOA genotype.
AB  - Previous research has reported that a functional polymorphism in the monoamine
      oxidase A (MAOA) gene promoter can moderate the association between early life
      adversity and increased risk for violence and antisocial behavior. In this study
      of a combined population of psychiatric outpatients and healthy volunteers (N =
      235), we tested the hypothesis that MAOA genotype moderates the association
      between early traumatic life events (ETLE) experienced during the first 15 years
      of life and the display of physical aggression during adulthood, as assessed by
      the Aggression Questionnaire. An ANOVA model including gender, exposure to early
      trauma, and MAOA genotype as between-subjects factors showed significant
      MAOAxETLE (F(1,227) = 8.20, P = 0.005) and genderxMAOAxETLE (F(1,227) = 7.04, P =
      0.009) interaction effects. Physical aggression scores were higher in men who had
      experienced early traumatic life events and who carried the low MAOA activity
      allele (MAOA-L). We repeated the analysis in the subgroup of healthy volunteers
      (N = 145) to exclude that the observed GxE interactions were due to the inclusion
      of psychiatric patients in our sample and were not generalizable to the
      population at large. The results for the subgroup of healthy volunteers were
      identical to those for the entire sample. The cumulative variance in the physical
      aggression score explained by the ANOVA effects involving the MAOA polymorphism
      was 6.6% in the entire sample and 12.1% in the sub-sample of healthy volunteers.
      Our results support the hypothesis that, when combined with exposure to early
      traumatic life events, low MAOA activity is a significant risk factor for
      aggressive behavior during adulthood and suggest that the use of dimensional
      measures focusing on behavioral aspects of aggression may increase the likelihood
      of detecting significant gene-by-environment interactions in studies of MAOA
      related aggression.

PMID- 17534437
TI  - A database of wing diversity in the Hawaiian Drosophila.
AB  - BACKGROUND: Within genus Drosophila, the endemic Hawaiian species offer some of
      the most dramatic examples of morphological and behavioral evolution. The advent
      of the Drosophila grimshawi genome sequence permits genes of interest to be
      readily cloned from any of the hundreds of species of Hawaiian Drosophila,
      offering a powerful comparative approach to defining molecular mechanisms of
      species evolution. A key step in this process is to survey the Hawaiian flies for
      characters whose variation can be associated with specific candidate genes. The
      wings provide an attractive target for such studies: Wings are essentially two
      dimensional, and genes controlling wing shape, vein specification, pigment
      production, and pigment pattern evolution have all been identified in Drosophila.
      METHODOLOGY/PRINCIPAL FINDINGS: We present a photographic database of over 180
      mounted, adult wings from 73 species of Hawaiian Drosophila. The image
      collection, available at FlyBase.org, includes 53 of the 112 known species of
      "picture wing" Drosophila, and several species from each of the other major
      Hawaiian groups, including the modified mouthparts, modified tarsus, antopocerus,
      and haleakalae (fungus feeder) groups. Direct image comparisons show that major
      wing shape changes can occur even between closely related species, and that
      pigment pattern elements can vary independently of each other. Among the 30
      species closest to grimshawi, diverse visual effects are achieved by altering a
      basic pattern of seven wing spots. Finally, we document major pattern variations
      within species, which appear to result from reduced diffusion of pigment
      precursors through the wing blade. CONCLUSIONS/SIGNIFICANCE: The database
      highlights the striking variation in size, shape, venation, and pigmentation in
      Hawaiian Drosophila, despite their generally low levels of DNA sequence
      divergence. In several independent lineages, highly complex patterns are derived
      from simple ones. These lineages offer a promising model system to study the
      evolution of complexity.

PMID- 17534438
TI  - Bax function in the absence of mitochondria in the primitive protozoan Giardia
      lamblia.
AB  - Bax-induced permeabilization of the mitochondrial outer membrane and release of
      cytochrome c are key events in apoptosis. Although Bax can compromise
      mitochondria in primitive unicellular organisms that lack a classical apoptotic
      machinery, it is still unclear if Bax alone is sufficient for this, or whether
      additional mitochondrial components are required. The protozoan parasite Giardia
      lamblia is one of the earliest branching eukaryotes and harbors highly
      degenerated mitochondrial remnant organelles (mitosomes) that lack a genome. Here
      we tested whether human Bax expressed in Giardia can be used to ablate mitosomes.
      We demonstrate that these organelles are neither targeted, nor compromised, by
      Bax. However, specialized compartments of the regulated secretory pathway are
      completely ablated by Bax. As a consequence, maturing cyst wall proteins that are
      sorted into these organelles are released into the cytoplasm, causing a
      developmental arrest and cell death. Interestingly, this ectopic cargo release is
      dependent on the carboxy-terminal 22 amino acids of Bax, and can be prevented by
      the Bax-inhibiting peptide Ku70. A C-terminally truncated Bax variant still
      localizes to secretory organelles, but is unable to permeabilize these membranes,
      uncoupling membrane targeting and cargo release. Even though mitosomes are too
      diverged to be recognized by Bax, off-target membrane permeabilization appears to
      be conserved and leads to cell death completely independently of mitochondria.

PMID- 17534439
TI  - Global surveillance of emerging Influenza virus genotypes by mass spectrometry.
AB  - BACKGROUND: Effective influenza surveillance requires new methods capable of
      rapid and inexpensive genomic analysis of evolving viral species for pandemic
      preparedness, to understand the evolution of circulating viral species, and for
      vaccine strain selection. We have developed one such approach based on previously
      described broad-range reverse transcription PCR/electrospray ionization mass
      spectrometry (RT-PCR/ESI-MS) technology. METHODS AND PRINCIPAL FINDINGS: Analysis
      of base compositions of RT-PCR amplicons from influenza core gene segments (PB1,
      PB2, PA, M, NS, NP) are used to provide sub-species identification and infer
      influenza virus H and N subtypes. Using this approach, we detected and correctly
      identified 92 mammalian and avian influenza isolates, representing 30 different H
      and N types, including 29 avian H5N1 isolates. Further, direct analysis of 656
      human clinical respiratory specimens collected over a seven-year period (1999
      2006) showed correct identification of the viral species and subtypes with >97%
      sensitivity and specificity. Base composition derived clusters inferred from this
      analysis showed 100% concordance to previously established clades. Ongoing
      surveillance of samples from the recent influenza virus seasons (2005-2006)
      showed evidence for emergence and establishment of new genotypes of circulating
      H3N2 strains worldwide. Mixed viral quasispecies were found in approximately 1%
      of these recent samples providing a view into viral evolution.
      CONCLUSION/SIGNIFICANCE: Thus, rapid RT-PCR/ESI-MS analysis can be used to
      simultaneously identify all species of influenza viruses with clade-level
      resolution, identify mixed viral populations and monitor global spread and
      emergence of novel viral genotypes. This high-throughput method promises to
      become an integral component of influenza surveillance.

PMID- 17534440
TI  - Experimental selection for Drosophila survival in extremely low O(2) environment.
AB  - BACKGROUND: Cellular hypoxia, if severe enough, results usually in injury or cell
      death. Our research in this area has focused on the molecular mechanisms
      underlying hypoxic tissue injury to explore strategies to prevent injury or
      enhance tolerance. The current experiments were designed to determine the genetic
      basis for adaptation to long term low O(2) environments. METHODOLOGY/PRINCIPAL
      FINDINGS: With long term experimental selection over many generations, we
      obtained a Drosophila melanogaster strain that can live perpetually in extremely
      low, normally lethal, O(2) condition (as low as 4% O(2)). This strain shows a
      dramatic phenotypic divergence from controls, including a decreased recovery time
      from anoxic stupor, a higher rate of O(2 )consumption in hypoxic conditions, and
      a decreased body size and mass due to decreased cell number and size. Expression
      arrays showed that about 4% of the Drosophila genome altered in expression and
      about half of the alteration was down-regulation. The contribution of some
      altered transcripts to hypoxia tolerance was examined by testing the survival of
      available corresponding P-element insertions (and their excisions) under
      extremely low O(2) conditions. We found that down-regulation of several candidate
      genes including Best1, broad, CG7102, dunce, lin19-like and sec6 conferred severe
      hypoxia tolerance in Drosophila. CONCLUSIONS/SIGNIFICANCE: We have identified a
      number of genes that play an important role in the survival of a selected
      Drosophila strain in extremely low O(2) conditions, selected by decreasing O(2)
      availability over many generations. Because of conservation of pathways, we
      believe that such genes are critical in hypoxia adaptation in physiological or
      pathological conditions not only in Drosophila but also in mammals.

PMID- 17534442
TI  - SNS-032 prevents tumor cell-induced angiogenesis by inhibiting vascular
      endothelial growth factor.
AB  - Cell proliferation, migration, and capillary network formation of endothelial
      cells are the fundamental steps for angiogenesis, which involves the formation of
      new blood vessels. The purpose of this study is to investigate the effect of a
      novel aminothiazole SNS-032 on these critical steps for in vitro angiogenesis
      using a coculture system consisting of human umbilical vein endothelial cells
      (HUVECs) and human glioblastoma cells (U87MG). SNS-032 is a potent selective
      inhibitor of cyclin-dependent kinases 2, 7, and 9, and inhibits both
      transcription and cell cycle. In this study, we examined the proliferation and
      viability of HUVECs and U87MG cells in the presence of SNS-032 and observed a
      dose-dependent inhibition of cellular proliferation in both cell lines. SNS-032
      inhibited threedimensional capillary network formations of endothelial cells. In
      a coculture study, SNS-032 completely prevented U87MG cell-mediated capillary
      formation of HUVECs. This inhibitor also prevented the migration of HUVECs when
      cultured alone or cocultured with U87MG cells. In addition, SNS-032 significantly
      prevented the production of vascular endothelial growth factor (VEGF) in both
      cell lines, whereas SNS-032 was less effective in preventing capillary network
      formation and migration of endothelial cells when an active recombinant VEGF was
      added to the medium. In conclusion, SNS-032 prevents in vitro angiogenesis, and
      this action is attributable to blocking of VEGF.

PMID- 17534441
TI  - 4-IBP, a sigma1 receptor agonist, decreases the migration of human cancer cells,
      including glioblastoma cells, in vitro and sensitizes them in vitro and in vivo
      to cytotoxic insults of proapoptotic and proautophagic drugs.
AB  - Although the molecular function of sigma receptors has not been fully defined and
      the natural ligand(s) is still not known, there is increasing evidence that these
      receptors and their ligands might play a significant role in cancer biology. 4-(N
      benzylpiperidin-4-yl)-4-iodobenzamide (4-IBP), a selective sigma1 agonist, has
      been used to investigate whether this compound is able to modify: 1) in vitro the
      migration and proliferation of human cancer cells; 2) in vitro the sensitivity of
      human glioblastoma cells to cytotoxic drugs; and 3) in vivo in orthotopic
      glioblastoma and non-small cell lung carcinoma (NSCLC) models the survival of
      mice co-administered cytotoxic agents. 4-IBP has revealed weak antiproliferative
      effects on human U373-MG glioblastoma and C32 melanoma cells but induced marked
      concentration-dependent decreases in the growth of human A549 NSCLC and PC3
      prostate cancer cells. The compound was also significantly antimigratory in all
      four cancer cell lines. This may result, at least in U373-MG cells, from
      modifications to the actin cytoskeleton. 4-IBP modified the sensitivity of U373
      MG cells in vitro to proapoptotic lomustin and proautophagic temozolomide, and
      markedly decreased the expression of two proteins involved in drug resistance:
      glucosylceramide synthase and Rho guanine nucleotide dissociation inhibitor. In
      vivo, 4-IBP increased the antitumor effects of temozolomide and irinotecan in
      immunodeficient mice that were orthotopically grafted with invasive cancer cells.

PMID- 17534443
TI  - Correlation of MRI biomarkers with tumor necrosis in Hras5 tumor xenograft in
      athymic rats.
AB  - Magnetic resonance imaging (MRI) can measure the effects of therapies targeting
      the tumor vasculature and has demonstrated that vascular-damaging agents (VDA)
      induce acute vascular shutdown in tumors in human and animal models. However, at
      subtherapeutic doses, blood flow may recover before the induction of significant
      levels of necrosis. We present the relationship between changes in MRI biomarkers
      and tumor necrosis. Multiple MRI measurements were taken at 4.7 T in athymic rats
      (n = 24) bearing 1.94 +/- 0.2-cm3 subcutaneous Hras5 tumors (ATCC 41000) before
      and 24 hours after clinically relevant doses of the VDA, ZD6126 (0-10 mg/kg,
      i.v.). We measured effective transverse relaxation rate (R2*), initial area under
      the gadolinium concentration-time curve (IAUGC(60/150)), equivalent enhancing
      fractions (EHF(60/150)), time constant (K(trans)), proportion of hypoperfused
      voxels as estimated from fit failures in K(trans) analysis, and signal intensity
      (SI) in T2-weighted MRI (T(2)W). ZD6126 treatment induced > 90% dose-dependent
      tumor necrosis at 10 mg/kg; correspondingly, SI changes were evident from T2W
      MRI. Although R2* did not correlate, other MRI biomarkers significantly
      correlated with necrosis at doses of > or = 5 mg/kg ZD6126. These data on Hras5
      tumors suggest that the quantification of hypoperfused voxels might provide a
      useful biomarker of tumor necrosis.

PMID- 17534444
TI  - Early changes in apparent diffusion coefficient predict the quantitative
      antitumoral activity of capecitabine, oxaliplatin, and irradiation in HT29
      xenografts in athymic nude mice.
AB  - PURPOSE: The purpose of this study was to evaluate the possible use of changes in
      apparent diffusion coefficient (ADC) measured by magnetic resonance imaging for
      pretreatment prediction and early detection of tumor response in a mouse model
      during fractionated chemoradiotherapy. MATERIALS AND METHODS: Athymic mice with
      bilateral HT29 xenografts on rear flanks were allocated into three groups:
      control, capecitabine, and capecitabine and oxaliplatin. The left flanks of the
      mice received daily irradiation. T2 and diffusion images were acquired before
      therapy and weekly for the following 9 weeks. Pretreatment and changes in ADC
      were calculated and compared with tumor doubling growth delay. RESULTS: No
      correlations between pretreatment ADC and changes in tumor volumes after therapy
      were seen. All treated tumors, except those receiving capecitabine (P = .06),
      showed increased mean tumor ADC values 11 days after initialization of therapy (P
      < .05) before returning to pretreatment values within 5 days posttherapy (day 18
      after onset of therapy). This increase in mean tumor ADC showed a strong positive
      correlation (r = 0.92, P < .01) with mean tumor doubling growth delay.
      CONCLUSIONS: Pretreatment ADC values did not predict the effectiveness of
      therapy, whereas early changes in mean ADC quantitatively correlated with
      treatment outcome.

PMID- 17534445
TI  - Chemopreventive effect of aerosolized polyphenon E on lung tumorigenesis in A/J
      mice.
AB  - Effective chemoprevention of lung cancer in high-risk patients through the
      administration of pharmacologic or nutritional agents is urgently needed. Aerosol
      inhalation can deliver chemopreventive agents directly to the respiratory tract
      to inhibit the tumorigenic process. In this study, polyphenon E (PolyE) and (-)
      epigallocatechin-3-gallate (EGCG) were administered by aerosol delivery to A/J
      mice beginning 2 weeks after carcinogen treatment and continuing daily by
      inhalation throughout the remainder of the study (20 weeks). PolyE decreased
      tumor load by approximately 59%. However, EGCG, both at the same dose and at a
      higher dose, failed to inhibit lung carcinogenesis. These results indicate that
      aerosol delivery of PolyE, but not EGCG, may be a useful chemopreventive protocol
      in subjects at high risk for lung cancer.

PMID- 17534446
TI  - Membrane-type 1 matrix metalloproteinase is regulated by sp1 through the
      differential activation of AKT, JNK, and ERK pathways in human prostate tumor
      cells.
AB  - We and other investigators have previously shown that membrane-type 1 matrix
      metalloproteinase (MT1-MMP) is overexpressed in invasive prostate cancer cells.
      However, the mechanism for this expression is not known. Here, we show that MT1
      MMP is minimally expressed in nonmalignant primary prostate cells, moderately
      expressed in DU-145 cells, and highly expressed in invasive PC-3 and PC-3N cells.
      Using human MT1-MMP promoter reporter plasmids and mobility shift assays, we show
      that Sp1 regulates MT1-MMP expression in DU-145, PC-3, and PC-3N cells and in PC3
      N cells using chromatin immunoprecipitation analysis and silencing RNA.
      Investigation of signaling pathway showed that DU-145 cells express
      constitutively phosphorylated extracellular stress-regulated kinase (ERK),
      whereas PC-3 and PC-3N cells express constitutively phosphorylated AKT/PKB and c
      Jun NH2 terminal kinase (JNK). We show that MT1-MMP and Sp1 levels are decreased
      in PC-3 and PC-3N cells when phosphatidylinositol-3 kinase and JNK are inhibited,
      and that MT1-MMP levels are decreased in DU-145 cells when MEK is inhibited.
      Transient transfection of PC-3 and PC-3N cells with a dominant-negative JNK or
      p85, and of DU-145 cells with a dominant negative ERK, reduces MT1-MMP promoter
      activity. These results indicate differential signaling control of Sp1-mediated
      transcriptional regulation of MT1-MMP in prostate cancer cell lines.

PMID- 17534448
TI  - Restoration of p53 expression in human cancer cell lines upregulates the
      expression of Notch1: implications for cancer cell fate determination after
      genotoxic stress.
AB  - Following genotoxic stress, transcriptional activation of target genes by p53
      tumor suppressor is critical in cell fate determination. Here we report that the
      restoration of p53 function in human cancer cell lines that are deficient in p53
      function upregulated the expression of Notch1. Interestingly, the expression of
      wild-type p53 in human prostate and breast cancer cell lines correlated well with
      increased expression of Notch1. Furthermore, knockdown of p53 expression in
      cancer cells that express wild-type p53 resulted in reduced expression of Notch1.
      Importantly, genotoxic stress to cancer cells that resulted in activation of p53
      also upregulated the expression of Notch1. Moreover, p53-mediated induction of
      Notch1 expression was associated with stimulation of the activity of Notch
      responsive reporters. Notably, p53 differentially regulated the expression of
      Notch family members: expression of Notch2 and Notch4 was not induced by p53.
      Significantly, treatment of cells with gamma secretase inhibitor, an inhibitor of
      Notch signaling, increased susceptibility to apoptosis in response to genotoxic
      stress. Together, our observations suggest that p53-mediated upregulation of
      Notch1 expression in human cancer cell lines contributes to cell fate
      determination after genotoxic stress.

PMID- 17534447
TI  - Fibroblast stimulation of blood vessel development and cancer cell invasion in a
      subrenal capsule xenograft model: stress-induced premature senescence does not
      increase effect.
AB  - Fibroblast cooperation with cancer cells in xenograft development was
      investigated by transplanting MDA-MB-231 cells under the kidney capsule of
      immunodeficient mice. Control fibroblasts and fibroblasts subjected to stress
      induced premature senescence by treatment with bleomycin were used. In other
      xenograft models, senescent fibroblasts have shown a growth-stimulatory effect
      greater than that of control cells. In this model, both types of fibroblasts
      accelerated the formation and growth of xenografts. Blood vessel development, as
      evidence by von Willebrand factor staining, was greatly accelerated by the
      presence of fibroblasts, and invasion into the kidney was also increased. Control
      and senescent fibroblasts had very similar effects. These actions of fibroblasts
      were partially recapitulated in in vitro experiments. Both control and senescent
      fibroblasts stimulated the tubulogenesis of endothelial cells in culture and
      stimulated the invasion of MDA-MB-231 cells through Matrigel in vitro. In this
      xenograft model, in which fibroblasts are cotransplanted with a cancer cell into
      an internal organ rather than subcutaneously, senescence was not an important
      factor in the effects of cotransplanted fibroblasts on growth, blood vessel
      development, and invasion. Therefore, cancer promotion by the senescence of
      adjacent stromal cells may be restricted to certain organ and tissue types.

PMID- 17534449
TI  - Tumor therapy mediated by lentiviral expression of shBcl-2 and S-TRAIL.
AB  - Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) can selectively
      kill tumor cells and, in combination with other agents, could enhance tumor
      therapy. We explored the combined therapeutic effects of a secretable form of (S)
      TRAIL-induced apoptosis and the downregulation of Bcl-2 in human gliomas. We
      constructed a lentiviral delivery system: 1) for the expression of short hairpin
      (sh) RNA to downregulate Bcl-2 and for the expression of S-TRAIL to induce
      apoptosis in glioma cells; and 2) to follow delivery in vitro and the fate of
      tumors in real time in vivo. We demonstrate that lentiviral-mediated simultaneous
      downregulation of Bcl-2 and S-TRAIL-induced apoptosis leads to an increased
      expression of activated caspase-3 and caspase-7, thus resulting in accelerated S
      TRAIL-mediated apoptosis in glioma cells in vitro. Using a highly malignant human
      glioma model expressing EGFRvIII and firefly luciferase, we show that the
      combined effect of Bcl-2 downregulation and S-TRAIL-induced apoptosis results in
      complete eradication of gliomas compared to S-TRAIL monotherapy. These results
      show that simultaneous triggering of TRAIL-mediated death receptor pathway and
      downregulation of Bcl-2 by shRNA leads to enhanced eradication of gliomas and
      serves as a template in developing and monitoring combination therapies for the
      treatment of drug-resistant cancers.

PMID- 17534450
TI  - Molecular concepts analysis links tumors, pathways, mechanisms, and drugs.
AB  - Global molecular profiling of cancers has shown broad utility in delineating
      pathways and processes underlying disease, in predicting prognosis and response
      to therapy, and in suggesting novel treatments. To gain further insights from
      such data, we have integrated and analyzed a comprehensive collection of
      "molecular concepts" representing > 2500 cancer-related gene expression
      signatures from Oncomine and manual curation of the literature, drug treatment
      signatures from the Connectivity Map, target gene sets from genome-scale
      regulatory motif analyses, and reference gene sets from several gene and protein
      annotation databases. We computed pairwise association analysis on all 13,364
      molecular concepts and identified > 290,000 significant associations, generating
      hypotheses that link cancer types and subtypes, pathways, mechanisms, and drugs.
      To navigate a network of associations, we developed an analysis platform, the
      Molecular Concepts Map. We demonstrate the utility of the approach by
      highlighting molecular concepts analyses of Myc pathway activation, breast cancer
      relapse, and retinoic acid treatment.

PMID- 17534451
TI  - [Health related quality of life in medical doctors: study of a sample of
      Uruguayan professionals].
AB  - Medical profession has been recognized as a health risk population due to
      inherent work characteristics as well as relatively recent changes in medical
      practice. However few studies refer to Physicians' Health-Related Quality of Life
      (HRQL). Present study analyzes HRQL of 145 medical doctors participating in
      Continuous Medical Education courses in Uruguay. Participants completed WHOQOL
      Bref, Maslach Burnout Inventory and a list of work-related interfering factors.
      Results show lower HRQL, especially in psychological and physical domains in
      those suffering burnout syndrome and also those who exhibit only emotional
      exhaustion or depersonalization. Factors explaining low psychological well being
      are related to work disruptive effects on personal life, because of irritability,
      lack of enjoyment and excessive work hours. The importance of protecting factors
      is also confirmed. Doctors considering their work as giving them valuable things,
      keeping motivation for work and empathy towards patients, exhibit better HRQL.
      Social, educational, organizational and individual factors that might influence
      on the situation are analyzed. The need of longitudinal studies to confirm the
      results is emphasized. Possible measures in these different levels are proposed.
      The ultimate goal is to favour a reflexive and gratifying practice, setting the
      basis of a new contract between doctors and society.

PMID- 17534452
TI  - [Psychotropic medication consumption in the general population of the Great
      Buenos Aires metropolitan area. Comparison between different areas and with
      Buenos Aires city].
AB  - OBJECTIVE: The purpose of this study was to estimate the prevalence of
      psychotropic drug consumption among the Great Buenos Aires general population and
      to compare this prevalence between its different areas and with Buenos Aires
      city. METHODS: A survey was conducted among 1877 inhabitants of different
      districts of the Great Buenos Aires Metropolitan Area. RESULTS: At the time of
      the survey, 7 % of the general population was using some kind of psychotropic
      medication. Utilization was higher in women, the elderly and individuals of
      middle or high social class and educational level extremes. Almost 10 percent of
      the consumers was using the medication without medical advice, and 35.6%
      recognized themselves as very dependent on these medications. Psychotropic drug
      utilization is higher in the North area (10.9% ) than in the West area (6.3% )
      and the South area (4.2%). The present percentage of psychotropic drug use in the
      Great Buenos Aires area is lower than half the one in Buenos Aires city, and it's
      more due to medical advice. These differences are not exclusively caused by
      demographic differences. CONCLUSIONS: Psychotropic drug use in the Great Buenos
      Aires Metropolitan Area is similar to other countries, but lower than in Buenos
      Aires city. Qualitive studies are needed to elucidate the causes of this
      difference.

PMID- 17534454
TI  - [International perspective on quality of life in older adults. The WHOQOL OLD
      project].
AB  - BACKGROUND: On a worldwide scale, the percentage of the population 60 years of
      age and older has increased considerably. Factors such as gender disparities,
      changes in family and social structure, the burden of illness and the risk of
      disability, among others, have awakened international interest in studying this
      age group's quality of life (QOL). The objective of the WHOQOL OLD Project was to
      develop a module for assessing the quality of life of older adults based on the
      existing WHOQOL OLD questionnaire. METHOD: Twenty three centers worldwide,
      together with the WHO, took part. Focal groups consisting of older adults,
      caretakers and professionals were formed. The groups consisted of 4 to 6
      participants who spoke openly and freely about their QOL, reviewed the WHOQOL 100
      to identify new facets and the facets previously defined as important by
      participating centers. RESULTS: All the areas of the WHOQOL 100 were considered
      important for QOL. Six additional facets were identified: sensory abilities;
      autonomy; past, present and future activities; involvement / withdrawal; death;
      and intimacy. CONCLUSION: The focus group methodology was useful for identifying
      the factors that contribute to older adults' quality of life. Developed under
      international consensus, it allows for QOL assessment from an international
      perspective.

PMID- 17534453
TI  - [Chronic disease and quality of life].
AB  - Chronic diseases could produce functional limitations in different domains as
      well as depression and anxiety. Health related quality of life (HRQL) measures
      could help to identify functional problems not detected by clinical evaluations.
      Those measures could also help to better understand different group conditions
      and situations. Main objectives of this paper are: to study the presence of
      depressive and anxiety status in out patients with chronic diseases and to
      investigate its association with a better or worse HRQL in different domains.
      MATERIALS AND METHODS: This is a prevalence design study. Patients were recruited
      from an university Hospital. Consecutive samples were collected from three
      medical specialties: Chronic pain, Parkinson's disease and Mental Health. Social
      and demographic data were collected. The SF 36 was administered for the HRQL
      evaluation and the Hospital Anxiety and Depression (HADS) for screening anxiety
      and depression states. Descriptive statistics and the chi square test were used
      for data analysis. RESULTS: 630 out patients were included. 25% of patients with
      chronic pain, 15% of patients with Parkinson disease and 31% with a mental health
      condition were classified with a probably depression. In the three groups of
      patients depression was found to be associated with physical function and
      emotional role, from the SF 36's dimensions. In the mental health and in
      Parkinson's disease out patients'groups, anxiety was associated to the majority
      of SF 36's dimensions. CONCLUSIONS: Results showed the complexity of the health
      phenomena and the relevance that HRQL measures and population norms have for
      comparing different health profiles for giving support either to clinicians or to
      health services practices.

PMID- 17534456
TI  - Wealth of nations is health of nations.

PMID- 17534457
TI  - Impact of World Hypertension Day.
AB  - It is estimated that nearly one billion people are affected by hypertension
      worldwide, and this figure is predicted to increase to 1.5 billion by 2025.
      Nearly one-half of this population are unaware of their condition. Hypertension
      is the primary risk factor for heart disease and stroke. World Hypertension Day
      (WHD) has been an initiative of the World Hypertension League to raise
      hypertension awareness. In the past two years, many countries have taken an
      active part in promoting awareness through a number of initiatives in their
      respective countries. In Canada, WHD was a resounding success in 2005 and 2006,
      and major plans are underway for WHD 2007. The success of the Canadian WHD
      depends mainly on the partnership and shared values of all stakeholders,
      including professional societies, nongovernment organizations, government
      agencies and industry. Although it is too early to assess the impact of
      hypertension, it is evident that the countries involved are taking hypertension
      in the population seriously and are moving in the right direction. If the
      momentum continues, a drastic reduction in the prevalence of worldwide
      hypertension can be anticipated.

PMID- 17534458
TI  - The 2007 Canadian Hypertension Education Program recommendations: the scientific
      summary - an annual update.
AB  - The present paper summarizes and highlights key messages of the 2007 Canadian
      Hypertension Education Program recommendations for the management and diagnosis
      of hypertension. This is the eighth annual update. Important new messages in the
      2007 Canadian Hypertension Education Program recommendations emphasize the need
      for assessing adults with high normal blood pressure on an annual basis and
      reducing sodium in the diet of Canadians to less than 100 mmol/day. These new
      recommendations still need to be incorporated into the older but still important
      considerations for the diagnosis, management and treatment of patients with
      hypertension, namely, assessing blood pressure in all adults at all appropriate
      visits, expediting the diagnosis of hypertension, assessing and managing global
      cardiovascular risk, emphasizing that lifestyle modifications are the cornerstone
      of antihypertensive therapy, treating to target to achieve optimum cardiovascular
      risk reduction, using combinations of antihypertensive medications and lifestyle
      to achieve recommended targets and focusing on adherence to therapy. Minor
      changes in pharmacological therapies and some new recommendations on routine
      laboratory tests are discussed.

PMID- 17534459
TI  - The 2007 Canadian Hypertension Education Program recommendations for the
      management of hypertension: part 1- blood pressure measurement, diagnosis and
      assessment of risk.
AB  - OBJECTIVE: To provide updated, evidence-based recommendations for the diagnosis
      and assessment of adults with hypertension. OPTIONS AND OUTCOMES: The diagnosis
      of hypertension is dependent on the appropriate measurement of blood pressure,
      the timely assessment of serially elevated readings, the degree of blood pressure
      elevation, the method of measurement (office, ambulatory, home) and any
      associated comorbidities. The presence of cardiovascular risk factors and target
      organ damage should be ascertained to assess global cardiovascular risk, and to
      determine the urgency, intensity and type of treatment required. EVIDENCE:
      MEDLINE searches were conducted from November 2005 to October 2006 with the aid
      of a medical librarian. Reference lists were scanned, experts were contacted, and
      the personal files of authors and subgroup members were used to identify
      additional studies. Content and methodological experts assessed studies using
      prespecified, standardized evidence-based algorithms. Recommendations were based
      on evidence from peer-reviewed, full-text articles only. RECOMMENDATIONS:
      Recommendations for blood pressure measurement, criteria for hypertension
      diagnosis and follow-up, assessment of global cardiovascular risk, diagnostic
      testing, diagnosis of renovascular and endocrine causes of hypertension, home and
      ambulatory monitoring, and the use of echocardiography in hypertensive
      individuals are outlined. Key messages in 2007 include continued emphasis on the
      expedited, accurate diagnosis of hypertension, the importance of assessing the
      risk of cerebrovascular events as part of global risk assessment, the need for
      ongoing reassessment of patients with high normal blood pressure, and reviews of
      recent studies involving laboratory testing and home monitoring. VALIDATION: All
      recommendations were graded according to strength of the evidence and were voted
      on by the 57 members of the Canadian Hypertension Education Program Evidence
      Based Recommendations Task Force. All recommendations reported here received at
      least 70% consensus. These guidelines will continue to be updated annually.

PMID- 17534461
TI  - The Canadian Hypertension Education Program - a unique Canadian knowledge
      translation program.
AB  - The Canadian Hypertension Education Program annually appraises data from
      hypertension research and updates clinical practice recommendation for the
      diagnosis and management of hypertension. Enormous effort is devoted to
      disseminating these recommendations to target groups throughout the country and,
      through the use of institutional databases, to evaluating their effectiveness in
      improving the health of Canadians by lowering blood pressure in people with
      hypertension. The mission of the Canadian Hypertension Education Program is to
      reduce the impact of hypertension on cardiovascular disease in Canada.

PMID- 17534460
TI  - The 2007 Canadian Hypertension Education Program recommendations for the
      management of hypertension: part 2 - therapy.
AB  - OBJECTIVE: To provide updated, evidence-based recommendations for the prevention
      and management of hypertension in adults. OPTIONS AND OUTCOMES: For lifestyle and
      pharmacological interventions, evidence was reviewed from randomized controlled
      trials and systematic reviews of trials. Changes in cardiovascular morbidity and
      mortality were the primary outcomes of interest. However, for lifestyle
      interventions, blood pressure lowering was accepted as a primary outcome given
      the lack of long-term morbidity and mortality data in this field. For treatment
      of patients with kidney disease, the progression of kidney dysfunction was also
      accepted as a clinically relevant primary outcome. EVIDENCE: A Cochrane
      collaboration librarian conducted an independent MEDLINE search from 2005 to
      August 2006 to update the 2006 Canadian Hypertension Education Program
      recommendations. In addition, reference lists were scanned and experts were
      contacted to identify additional published studies. All relevant articles were
      reviewed and appraised independently by both content and methodological experts
      using prespecified levels of evidence. RECOMMENDATIONS: Dietary lifestyle
      modifications for prevention of hypertension, in addition to a well-balanced
      diet, include a dietary sodium intake of less than 100 mmol/day. In hypertensive
      patients, the dietary sodium intake should be limited to 65 mmol/day to 100
      mmol/day. Other lifestyle modifications for both normotensive and hypertensive
      patients include: performing 30 min to 60 min of aerobic exercise four to seven
      days per week; maintaining a healthy body weight (body mass index of 18.5 kg/m2
      to 24.9 kg/m2) and waist circumference (less than 102 cm in men and less than 88
      cm in women); limiting alcohol consumption to no more than 14 units per week in
      men or nine units per week in women; following a diet reduced in saturated fat
      and cholesterol, and one that emphasizes fruits, vegetables and low-fat dairy
      products, dietary and soluble fibre, whole grains and protein from plant sources;
      and considering stress management in selected individuals with hypertension. For
      the pharmacological management of hypertension, treatment thresholds and targets
      should take into account each individual's global atherosclerotic risk, target
      organ damage and any comorbid conditions: blood pressure should be lowered to
      lower than 140/90 mmHg in all patients and lower than 130/80 mmHg in those with
      diabetes mellitus or chronic kidney disease. Most patients require more than one
      agent to achieve these blood pressure targets. In adults without compelling
      indications for other agents, initial therapy should include thiazide diuretics;
      other agents appropriate for first-line therapy for diastolic and/or systolic
      hypertension include angiotensin-converting enzyme (ACE) inhibitors (except in
      black patients), long-acting calcium channel blockers (CCBs), angiotensin
      receptor blockers (ARBs) or beta-blockers (in those younger than 60 years of
      age). First-line therapy for isolated systolic hypertension includes long-acting
      dihydropyridine CCBs or ARBs. Certain comorbid conditions provide compelling
      indications for first-line use of other agents: in patients with angina, recent
      myocardial infarction, or heart failure, beta-blockers and ACE inhibitors are
      recommended as first-line therapy; in patients with cerebrovascular disease, an
      ACE inhibitor plus diuretic combination is preferred; in patients with
      nondiabetic chronic kidney disease, ACE inhibitors are recommended; and in
      patients with diabetes mellitus, ACE inhibitors or ARBs (or, in patients without
      albuminuria, thiazides or dihydropyridine CCBs) are appropriate first-line
      therapies. All hypertensive patients with dyslipidemia should be treated using
      the thresholds, targets and agents outlined in the Canadian Cardiovascular
      Society position statement (recommendations for the diagnosis and treatment of
      dyslipidemia and prevention of cardiovascular disease). Selected high-risk
      patients with hypertension who do not achieve thresholds for statin therapy
      according to the position paper should nonetheless receive statin therapy. Once
      blood pressure is controlled, acetylsalicylic acid therapy should be considered.
      VALIDATION: All recommendations were graded according to strength of the evidence
      and voted on by the 57 members of the Canadian Hypertension Education Program
      Evidence-Based Recommendations Task Force. All recommendations reported here
      achieved at least 95% consensus. These guidelines will continue to be updated
      annually.

PMID- 17534462
TI  - Canada Chair in hypertension prevention and control: a pilot project.
AB  - A five-year pilot project was initiated in Canada to fund an individual to lead
      the effort in improving hypertension prevention and control. As the initial
      recipient of the funding, the author's objectives were to provide leadership to
      improve the management of hypertension through enhancements to the Canadian
      Hypertension Education Program, to increase public knowledge of hypertension, to
      reduce the prevalence of hypertension by reducing dietary sodium additives and to
      develop a comprehensive hypertension surveillance program. The initiative has
      received strong support from the hypertension community, the Public Health Agency
      of Canada, the Heart and Stroke Foundation of Canada, and many Canadian health
      care professional and scientific organizations. Progress has been made on all
      objectives. The pilot project was funded by The Canadian Hypertension Society,
      the Canadian Institutes of Health Research and sanofi-aventis, in partnership
      with Blood Pressure Canada, and will finish in July 2011.

PMID- 17534463
TI  - Antihypertensive medication use by recently diagnosed hypertensive Canadians.
AB  - PURPOSE: The Canadian Hypertension Education Program (CHEP) was initiated in 1999
      to improve hypertension management in Canada. The objective of the present study
      was to compare antihypertensive pharmacotherapy in Canada before and after the
      CHEP. METHODS: Data were obtained from the longitudinal National Population
      Health Surveys, which consisted of five cycles at two-year intervals from 1994 to
      2002. Recent hypertensive respondents 20 years of age and older were identified
      the first time hypertension was reported or treated, and were included in a study
      population of 1453 newly diagnosed hypertensive patients. Persistence with
      medication use was assessed in the cycle after the first report of hypertension.
      RESULTS: Antihypertensive medication use within two years of hypertension
      diagnosis increased with age, from 35% in patients 20 to 39 years of age, to
      72.1% in those 80 years of age and older. Antihypertensive medication use
      increased after the CHEP (from 49.2% to 53.8% of the population), as did the use
      of multiple antihypertensive medications (from 7.5% to 10.6%). The most commonly
      used antihypertensive medication for men was angiotensin-converting enzyme
      inhibitors (beta-blockers were second), but the most common medication for women
      was diuretics. The overall persistence rate for antihypertensive medication use
      was 73.2% over two years, which had increased after the CHEP (from 70.4% to
      75.4%). CONCLUSIONS: The implementation of the CHEP was followed by increased
      antihypertensive medication use, increased use of multiple antihypertensive
      medications and improved persistence with medication use. Although causality
      cannot be established with the design of the present study, improved hypertension
      management in Canada is heartening. Sex-related differences were observed in
      prescribed medications, even though clinical guidelines do not differentiate
      between sexes.

PMID- 17534464
TI  - Dietary sodium and cardiovascular outcomes: a rational approach.
AB  - Hypertension, the leading risk factor for mortality in the world, affects nearly
      one in four Canadians. There is substantive evidence that high dietary sodium
      contributes to hypertension. Animal studies consistently demonstrate increased
      blood pressure and cardiovascular morbidity and mortality with high dietary
      sodium intake. Evidence of the adverse health effects in humans associated with
      increased sodium intake is accumulating rapidly. Previously, limitations on
      sodium consumption were recommended only for those identifiable groups of people
      shown to be at higher risk. With the lifetime risk of developing hypertension
      being more than 90% in an average lifespan, the need for a population-based
      approach to reducing hypertension is clear. The present paper reviews the
      evidence of sodium and cardiovascular disease, resulting in the 2007 Canadian
      Hypertension Education Program recommendation of daily intake of less than 100
      mmol of sodium in both normotensive and hypertensive adults.

PMID- 17534465
TI  - More medications, fewer pills: combination medications for the treatment of
      hypertension.
AB  - Achieving blood pressure targets in hypertension can be challenging. Often,
      patients require multiple medications to reach these targets. The Canadian
      Hypertension Education Program has updated its past recommendations to reflect
      current knowledge regarding effective antihypertensive combinations. Evidence for
      the use of specific drug combinations in achieving blood pressure targets has
      been reviewed, and the inventory of effective drug combinations has been
      expanded. From a clinical perspective, fixed-dose antihypertensive combinations
      offer certain advantages in terms of efficacy, adherence, cost, convenience,
      patient-perceived 'wellness' and side effects. Consequently, in the future, fixed
      dose combination formulations are likely to become increasingly used in the
      treatment of cardiovascular disease.

PMID- 17534466
TI  - Practical advice for home blood pressure measurement.
AB  - Early diagnosis of hypertension is one benefit of home blood pressure monitoring.
      Home measurement may also be used for the detection of masked hypertension. Home
      blood pressure readings have a strong correlation with risk, and the method has
      many advantages over office measurement in the management of hypertension,
      especially in patients with chronic kidney disease or diabetes. The present
      article provides practical advice on incorporating home blood pressure monitoring
      into practice. Patient education and training are discussed, as are tips to aid
      in the selection of devices for blood pressure measurement at home.

PMID- 17534467
TI  - High normal blood pressure and prehypertension: the debate continues.
AB  - Subjects with high normal blood pressure are at high risk of developing
      hypertension. Thus, the criteria of the Canadian Hypertension Education Program
      for diagnosis of hypertension and recommendations for follow-up now recommend
      that patients with high normal blood pressure (130 mmHg to 139 mmHg systolic
      and/or 85 mmHg to 89 mmHg diastolic) be followed up annually for the development
      of hypertension. Clinical trial data from subjects with high normal blood
      pressure show that 40% over two years and 63% over four years developed
      hypertension (140/90 mmHg or higher). These data are consistent with
      observational data from the Framingham Heart Study, which found a similar risk.
      Besides annual follow-up, the Canadian Hypertension Education Program recommends
      lifestyle therapy for individuals with high normal blood pressure. Ongoing
      research will establish whether any further management is required.

PMID- 17534469
TI  - Telemanagement of hypertension: a qualitative assessment of patient and physician
      preferences.
AB  - BACKGROUND: Prevalence surveys have consistently found that the blood pressure
      control rate among people with hypertension is less than 25%. Studies of
      telemedicine as a means of providing care to hypertensive patients have shown
      that this approach is effective in lowering blood pressure. Major design flaws
      and high operating costs, however, have hindered its adoption by physicians and
      patients. OBJECTIVES: In the present commentary, the field of telemedicine, as it
      pertains to hypertension management, is reviewed, and the investigators'
      experiences in developing a new telemedicine system are outlined. METHODS: An
      applied qualitative case study approach was used to determine the information
      needs for the design of a telemedicine system. Opinions were elicited separately
      from type 2 diabetic patients with hypertension (n=24) and family practitioners
      in active clinical practice (n=18). RESULTS: Physician and patient focus group
      meetings provided key information that led to changes in the prototype system.
      The low level of computer and Internet use by patients in everyday life and by
      physicians in practice-related activities precluded their inclusion in the design
      of the system for information retrieval and receiving clinical alerts. For
      patients, the mobile phone appeared to be an acceptable alternative. The only
      practical, automated means to disseminate reports and alerts to physicians was by
      fax, which was the most universally available device in a doctor's office.
      CONCLUSION: This tightly focused qualitative study led to the development of
      design principles for a prototype system, increasing the likelihood of user
      acceptance and improving its effectiveness.

PMID- 17534468
TI  - Improving outcomes in diabetes and chronic kidney disease: the basis for Canadian
      guidelines.
AB  - The prevalence of diabetes is on the rise in Canada, and there has been a
      corresponding increase in the rate of micro- and macrovascular complications.
      Among the worst of these is chronic kidney disease (CKD). It may be diagnosed
      either through the detection of persistent albuminuria or an estimated glomerular
      filtration rate that is persistently less than 60 mL/min/1.73 m2. Patients with
      diabetes and CKD have a lower quality of life and higher health care costs, and
      face the prospect of end-stage renal disease requiring dialysis. More
      importantly, this group has an extremely elevated cardiovascular risk and
      correspondingly reduced survival. Research over several decades has led to two
      important conclusions. First, progressive worsening of kidney disease is not
      inevitable in people with diabetes; it can be slowed or even stopped. Second, the
      elevated cardiovascular risk in this population can be significantly reduced
      through an aggressive approach to cardiovascular risk factor reduction. These
      conclusions have prompted Canadian guideline groups, such as the Canadian
      Diabetes Association and the Canadian Hypertension Education Program, to release
      clinical practice guidelines that address the management of people with diabetes
      and CKD. In the present article, the studies that have influenced these Canadian
      guidelines are examined, and areas in which further research is still required
      are identified.

PMID- 17534470
TI  - Treatment of hypertension in patients with nondiabetic chronic kidney disease.
AB  - Hypertension is highly prevalent in patients with chronic kidney disease (CKD).
      As either the cause or the consequence of CKD, hypertension is an important
      independent factor determining the rate of loss of renal function. Hypertension
      is also a significant independent risk factor for cardiovascular events in
      patients with CKD, the leading cause of their morbidity and mortality. Based on
      evidence from observational cohort studies and randomized clinical trials, the
      Canadian Hypertension Education Program (CHEP) recommends a target blood pressure
      (BP) of lower than 130/80 mmHg in hypertensive patients with nondiabetic CKD. The
      CHEP also endorses the use of renin-angiotensin system blockers for the BP
      lowering regimen in nondiabetic patients with CKD and significant proteinuria. It
      is recognized that the majority of nondiabetic patients with CKD will require two
      or more BP-lowering drugs to attain target BP. Furthermore, extracellular fluid
      volume expansion is a major contributor to hypertension in patients with CKD, and
      diuretics should be part of the BP-lowering regimen in the majority of patients.
      Patients with CKD are recognized to be at high risk for cardiovascular events,
      and studies testing new emerging treatments of hypertension to reduce the burden
      of CKD on renal and cardiovascular outcomes are underway. In this regard, the
      CHEP will continue to review and update all its recommendations annually.

PMID- 17534471
TI  - Cyclic porphyrin arrays as artificial photosynthetic antenna: synthesis and
      excitation energy transfer.
AB  - Covalently linked cyclic porphyrin arrays have been explored in recent years as
      artificial photosynthetic antenna. In this review we present the fundamental
      aspects of covalently linked cyclic porphyrin arrays by highlighting recent
      progress. The major emphasis of this tutorial review lies on the synthetic
      method, the structure, and the excitation energy transfer (EET) of such arrays.
      The final cyclization steps were often performed with the aid of templates.
      Efficient EET along the wheel is observed in these cyclic arrays, but ultrafast
      EET processes with rates of <1 ps, which rival those in the natural LH2, are rare
      and have been identified only in cyclic arrays 30-32 composed of directly meso
      meso linked porphyrins.

PMID- 17534472
TI  - Solvent-free synthesis of metal complexes.
AB  - Avoiding the use of solvents in synthesis can reduce environmental contamination
      and even be more convenient than using solvent-based synthesis. In this tutorial
      review we focus on recent research into the use of mechanochemistry (grinding) to
      synthesise metal complexes in the absence of solvent. We include synthesis of
      mononuclear complexes, coordination clusters, spacious coordination cages, and 1
      , 2- and 3-dimensional coordination polymers (metal organic frameworks) which can
      even exhibit microporosity. Remarkably, in many cases, mechanochemical synthesis
      is actually faster and more convenient than the original solvent-based methods.
      Examples of solvent-free methods other than grinding are also briefly discussed,
      and the positive outlook for this growing topic is emphasised.

PMID- 17534473
TI  - Locking self-assembly: strategies and outcomes.
AB  - In the last ten to fifteen years, self-assembly has been increasingly employed to
      construct discrete supramolecular structures. In most cases, due to the
      thermodynamic factors that drive the self-assembly process, the final
      architectures produced by this approach are not kinetically robust. Thus, when
      robust structures are required a "self-assembly followed by covalent
      modification" strategy has been commonly applied. However, over the last decade
      an alternative strategy has emerged. Several methods for "locking" self-assembly,
      and thus yielding kinetically inert products have been developed. This review
      outlines the main strategies that have been employed towards such aims and
      describes some of the properties that result from the enhanced stability of
      product architectures.

PMID- 17534474
TI  - Constraining molecules at the closest approach: chemistry at high pressure.
AB  - The purpose of this tutorial review is to illustrate the effects that the
      application of high pressures can have on chemical reactions involving highly
      compressible molecular materials. The essentials of the high-pressure technology
      (generation and in situ control of high pressures) are described with particular
      attention to the versatile diamond anvil cell (DAC) apparatus. The general
      effects of pressure on chemical equilibrium, reaction rate and reaction mechanism
      are discussed. The motivation for application of high-pressure methods (in the 1
      300 MPa range) to chemical synthesis and in biochemistry are illustrated focusing
      the attention on environmental effects and with an excursus on developing
      biotechnological applications. The peculiarities and the unexpected outcomes of
      chemical reactions occurring at very high pressures (>or=300 MPa) are discussed
      considering the extraordinary results obtained in polymerization and
      amorphization of simple molecules and of unsaturated hydrocarbons. The possible
      connection of the high temperature-high pressure thresholds for chemical
      reactions with microscopic counterparts (intermolecular distances, molecular
      orientations) is also discussed.

PMID- 17534475
TI  - Thermodynamics of actinide complexation in solution at elevated temperatures:
      application of variable-temperature titration calorimetry.
AB  - Studies of actinide complexation in solution at elevated temperatures provide
      insight into the effect of solvation and the energetics of complexation, and help
      to predict the chemical behavior of actinides in nuclear waste processing and
      disposal where temperatures are high. This tutorial review summarizes the data on
      the complexation of actinides at elevated temperatures and describes the
      methodology for thermodynamic measurements, with the emphasis on variable
      temperature titration calorimetry, a highly valuable technique to determine the
      enthalpy and, under appropriate conditions, the equilibrium constants of
      complexation as well.

PMID- 17534476
TI  - Multiconfigurational quantum chemical methods for molecular systems containing
      actinides.
AB  - Recent advances in computational actinide chemistry are reported in this tutorial
      review. Muticonfigurational quantum chemical methods have been employed to study
      the gas phase spectroscopy of small actinide molecules. Examples of actinide
      compounds studied in solution are also presented. Finally the multiple bond in
      the diuranium molecule and other diactinide compounds is described.

PMID- 17534477
TI  - Developments in accurate and traceable chemical measurements.
AB  - In recent years there has been considerable interest in the application of the
      principles of measurement science to chemistry. This has led to the recognition
      of 'metrology in chemistry' as an area of relevance to analytical chemistry
      research. This tutorial review describes the benefits to chemistry of the
      implementation of the principles of measurement science and explains how they are
      able to improve the reliability and accuracy of chemical measurements.

PMID- 17534478
TI  - Application of electronic circular dichroism in configurational and
      conformational analysis of organic compounds.
AB  - This tutorial review is addressed to readers with a background in basic organic
      chemistry and spectroscopy, but without a specific knowledge of electronic
      circular dichroism. It describes the fundamental principles, instrumentation,
      data analysis, and different approaches for interpretation of ECD. The discussion
      focuses on the application of ECD, also in combination with other methods, in
      structural analysis of organic compounds, including host-guest complexes, and
      will emphasize the importance of the interplay between configurational and
      conformational factors. The tutorial also covers modern supramolecular aspects of
      ECD and recent developments in computational methods.

PMID- 17534479
TI  - The chemical effects of molecular sol-gel entrapment.
AB  - Chemical conversions within the cages of doped sol-gel porous oxides take place
      with unique advantages over reactions in solution as the glassy matrix has
      tremendous effects on the reactivity of the entrapped molecules. The chemical
      properties of sol-gel materials can be tailored in an immense range of values and
      chemists are increasingly achieving control on reactions taking place within
      these matrices, including crucially important photovoltaics. Highlighting recent
      major advancements, we show in this tutorial review how this is actually taking
      place.

PMID- 17534480
TI  - Spontaneous resolution, whence and whither: from enantiomorphic solids to chiral
      liquid crystals, monolayers and macro- and supra-molecular polymers and
      assemblies.
AB  - One of the great challenges in stereochemistry is the explanation of why some
      molecules resolve spontaneously while others do not. In this critical review the
      recent advances in the creation of chiral systems from achiral and racemic
      compounds in three-, two- and one-dimensional systems are discussed. There are
      some groups of molecules in some systems that do tend to display conglomerates,
      which may suggest that there are enantiophobic and enantiophilic molecules whose
      assembly is guided by the structural and thermodynamic properties of the systems
      in question.

PMID- 17534481
TI  - Metals in membranes.
AB  - In this critical review we discuss recent advances in understanding the modes of
      interaction of metal ions with membrane proteins, including channels, pumps,
      transporters, ATP-binding cassette proteins, G-protein coupled receptors, kinases
      and respiratory enzymes. Such knowledge provides a basis for elucidating the
      mechanism of action of some classes of metallodrugs, and a stimulus for the
      further exploration of the coordination chemistry of metal ions in membranes.
      Such research offers promise for the discovery of new drugs with unusual modes of
      action. The article will be of interest to bioinorganic chemists, chemical
      biologists, biochemists, pharmacologists and medicinal chemists. (247
      references).

PMID- 17534482
TI  - Design of fluorescent materials for chemical sensing.
AB  - There is an enormous demand for chemical sensors for many areas and disciplines.
      High sensitivity and ease of operation are two main issues for sensor
      development. Fluorescence techniques can easily fulfill these requirements and
      therefore fluorescent-based sensors appear as one of the most promising
      candidates for chemical sensing. However, the development of sensors is not
      trivial; material science, molecular recognition and device implementation are
      some of the aspects that play a role in the design of sensors. The development of
      fluorescent sensing materials is increasingly captivating the attention of the
      scientists because its implementation as a truly sensory system is
      straightforward. This critical review shows the use of polymers, sol-gels,
      mesoporous materials, surfactant aggregates, quantum dots, and glass or gold
      surfaces, combined with different chemical approaches for the development of
      fluorescent sensing materials. Representative examples have been selected and
      they are commented here.

PMID- 17534483
TI  - Lanthanide-based emitting materials in light-emitting diodes.
AB  - Since the description of efficient electroluminescence from aluminium
      tris(hydroxyquinoline) in the mid 1980s, interest in new complexes and polymers
      with luminescence properties as emitting layers in light-emitting diodes has
      steadily increased. Recently, Ln(III) ion complexes have gained in importance for
      this type of application. Here we review some of the seminal work in the area,
      along with new developments in the field. The photophysical characterization of
      complexes of lanthanide ions both in solution and in the solid state allows the
      determination of which of the complexes might be successfully utilized as
      emitting layers in light-emitting diodes for display applications. However, the
      architecture of the device is also of major importance, to allow for good charge
      transport and recombination and thus obtain pure colors and high emission quantum
      efficiency.

PMID- 17534484
TI  - The first bona-fide sodium complex of hydrotris(methimazolyl)borate: an example
      of sodium exhibiting a preference for sulfur over oxygen.
AB  - The synthesis and structure of two related sodium complexes are reported which
      demonstrate that sulfur can preferentially complex to sodium irrespective of the
      presence of more apposite donor species such as DMF.

PMID- 17534485
TI  - A disymmetric terpyridine based ligand for the formation of luminescent di-aquo
      lanthanide complexes.
AB  - The synthesis of ligand H3 based on a disymmetrically substituted terpyridine
      core functionalised by a carboxylic acid in the 6-position and a
      bis(carboxymethyl)aminomethyl function in the 6''-position is described. The
      coordination behaviour of this heptadentate (4N/3O) ligand with lanthanide
      cations (Ln=Eu, Gd and Tb) was studied in solution showing the formation of
      complexes with [Ln] stoichiometry. Complexes with general formula [Ln(H2O)2] were
      isolated from neutral water solutions containing equimolar amounts of cations and
      ligands, and the complexes were characterized in the solid state (elemental
      analysis, IR) and in solution (mass spectrometry). The photo-physical properties
      of the luminescent complexes of Eu and Tb were studied in water solution by means
      of absorption, steady state and time-resolved emission spectroscopies. Evolution
      of the luminescence lifetimes of the Eu and Tb complexes in H2O and D2O reveals
      the presence of two water molecules coordinated in the first coordination sphere
      of the cations. Despite this important hydration number, the overall luminescence
      quantum yields of the complexes remained elevated, especially in the case of Tb
      (Phi=22.0 and 6.5% respectively for Tb and Eu). Upon crystallisation the Gd
      complex formed dimeric species in which two gadolinium atoms are each
      heptacoordinated by one ligand, the coordination sphere being completed by a
      single water molecule and a bridging carboxylate function, pointing to different
      behaviours in the solid and liquid states.

PMID- 17534486
TI  - Synthesis and reactivity of fluorinated ferracarborane anions.
AB  - The ferracarborane [N(PPh3)2][6,6,6,10,10,10-(CO)6-closo-6,10,1-Fe2CB7H8] reacts
      in CH2Cl2 with 3 molar equivalents of Ag[PF6] to yield the trifluoro-substituted
      species [N(PPh3)2][7,8,9-F3-6,6,6,10,10,10-(CO)6-closo-6,10,1-Fe2CB7H5]. Compound
      undergoes structural rearrangement in toluene at reflux temperatures, forming
      [N(PPh3)2][8,9,10-F3-6,6,6,7,7,7-(CO)6-closo-6,7,1-Fe2CB7H5]. Alternatively,
      reaction of either or with a 10-fold excess of Ag[PF6] in CH2Cl2 forms two
      species: namely, [N(PPh3)2][2,7,9,10-F4-6,6,6,8,8,8-(CO)6-closo-6,8,1-Fe2CB7H4],
      in which one further B-F substitution has occurred and the {Fe2CB7} cluster core
      has rearranged, plus a mono-iron co-product, [N(PPh3)2][3,8,9-F3-7,7,7-(CO)3
      closo-7,1-FeCB7H5] that is formed by polyhedral contraction. Treatment of with
      [NO][BF4] in CH2Cl2 results in CO substitution at the 4-connected iron vertex
      [Fe10], producing the zwitterionic complex [7,8,9-F3-6,6,6,10,10-(CO)5-10-NO
      closo-6,10,1-Fe2CB7H5]. Addition of Me3NO to a mixture of and PEt3 in CH2Cl2 also
      results in CO substitution, forming the isomeric species [N(PPh3)2][7,8,9-F3
      6,6,m,10,10-(CO)5-n-PEt3-closo-6,10,1-Fe2CB7H5] [m=6, n=10; m=10, n=6] in a 5:1
      ratio. Treatment of with [NO][BF4] and then CNBut in CH2Cl2 allows further,
      successive CO substitution at Fe10 to yield first a neutral, zwitterionic complex
      [7,8,9-F3-6,6,6,10-(CO)4-10-NO-10-PEt3-closo-6,10,1-Fe2CB7H5] and then [7,8,9-F3
      6,6,6-(CO)3-10-CNBut-10-NO-10-PEt3-closo-6,10,1-Fe2CB7H5]. The molecular
      structures of compounds and have been established by X-ray diffraction.

PMID- 17534488
TI  - Hydrothermal chemistry of oligomeric vanadium oxyfluorides.
AB  - Nine new vanadium oxyfluorides, containing ten different oligomeric vanadium
      (oxy)fluoride anions have been prepared by solvothermal synthesis in water
      ethylene glycol and using organic cations as co-crystallising agents. Crystal
      structures are reported for each. Amongst the ten structure types, five represent
      previously unobserved moieties, including one monomeric unit (cis-[VOF4(H2O)]2-),
      two dimers ([V2O2F6(H2O)2]2- and [V2O2F8]4-) and two tetramers (both isomers of
      composition [V4O4F14]6-). Structural relationships between the various units are
      discussed, together with some rationalisation of their occurrence as a function
      of synthetic variables.

PMID- 17534487
TI  - Synthesis, crystal structure, thermal and luminescence properties of CuX(2,3
      dimethylpyrazine) (X=Cl, Br, I) coordination polymers.
AB  - Three new coordination polymers based on CuI and 2,3-dimethylpyrazine (2,3-dmpyz)
      were prepared, structurally characterized and investigated for their thermal and
      luminescence properties. In the ligand rich 2:3 compound [(CuI)2(2,3-dmpyz)3]
      (CuI)2 dimers are found, which are connected by the N-donor ligands into chains,
      whereas in the structure of the 1:1 intermediate [(CuI)(2,3-dmpyz)] (CuI)4
      tetramers are found, which are also connected into chains. The crystal structure
      of the ligand deficient 2:1 compound [(CuI)2(2,3-dmpyz)] is built up of CuI
      double chains, which are connected by the 2,3-dmpyz ligands into layers. Thermal
      decomposition of results in its direct transformation into the ligand deficient
      compound , without the formation of the 1:1 compound as an intermediate. A
      similar thermal reactivity is found for compound , which transforms into on
      heating. Stirring of a crystalline suspension of pure or in acetonitrile, always
      leads to a transformation into the ligand deficient compound indicating that
      compound is the most stable of all the coordination polymers, whereas compounds
      and are metastable. The luminescence properties of the CuCl and CuI coordination
      polymers were investigated at 298 and 77K. It was observed that the emission
      maxima strongly depends on the nature of the halide atom and the composition and
      structure of the coordination polymers. In addition, several of these compounds
      show luminescence thermochromism. These results are compared with those obtained
      for the previously reported CuCl and CuBr(2,3-dimethylpyrazine) coordination
      polymers.

PMID- 17534489
TI  - Homobinuclear cyanide-bridged linkage isomers containing the redox-active unit
      [(micro-XY)Ru(CO)2L(o-O2C6Cl4)] (XY=CN or NC).
AB  - The salts [NEt4][Ru(CN)(CO)2L(o-O2C6Cl4)] {L=PPh3 or P(OPh)3}, which undergo one
      electron oxidation at the catecholate ligand to give neutral semiquinone
      complexes [Ru(CN)(CO)2L(o-O2C6Cl4)], react with the dimers [{Ru(CO)2L(micro-o
      O2C6Cl4)}2] {L=PPh3 or P(OPh)3} to give [NEt4][(o-O2C6Cl4)L(OC)2Ru(micro
      CN)Ru(CO)2L'(o-O2C6Cl4)] {L or L'=PPh3 or P(OPh)3}. The cyanide-bridged binuclear
      anions are, in turn, reversibly oxidised to isolable neutral and cationic
      complexes [(o-O2C6Cl4)L(OC)2Ru(micro-CN)Ru(CO)2L'(o-O2C6Cl4)] and [(o
      O2C6Cl4)L(OC)2Ru(micro-CN)Ru(CO)2L'(o-O2C6Cl4)]+ which contain one and two
      semiquinone ligands respectively. Structural studies on the redox pair [(o
      O2C6Cl4)(Ph3P)(OC)2Ru(micro-CN)Ru(CO)2(PPh3)(o-O2C6Cl4)]- and [(o
      O2C6Cl4)(Ph3P)(OC)2Ru(micro-CN)Ru(CO)2(PPh3)(o-O2C6Cl4)] confirm that the C-bound
      Ru(CO)2(o-O2C6Cl4) fragment is oxidised first. Uniquely, [(o
      O2C6Cl4){(PhO)3P}(OC)2Ru(micro-CN)Ru(CO)2(PPh3)(o-O2C6Cl4)]- is oxidised first at
      the N-bound fragment, indicating that it is possible to control the site of
      electron transfer by tuning the co-ligands. Crystallisation of [(o
      O2C6Cl4)(Ph3P)(OC)2Ru(micro-CN)Ru(CO)2{P(OPh)3}(o-O2C6Cl4)] resulted in the
      formation of an isomer in which the P(OPh)3 ligand is cis to the cyanide bridge,
      contrasting with the trans arrangement of the X-Ru-L fragment in all other
      complexes of the type RuX(CO)2L(o-O2C6Cl4).

PMID- 17534491
TI  - Supramolecular bidentate phosphorus ligands based on bis-zinc(II) and bis-tin(IV)
      porphyrin building blocks.
AB  - Selective metal-ligand interactions have been used to prepare supramolecular
      bidentate ligands by mixing monodentate ligands with a suitable template. For
      these assemblies pyridine phosphorus ligands and a zinc(II) porphyrin dimer were
      used. In the rhodium-catalysed hydroformylation of 1-octene and styrene improved
      selectivities have been obtained for some of the assembled bidentate ligand
      systems. In the palladium catalysed asymmetric allylic alkylation similar effects
      were observed; the enantioselectivity increased by using a bisporphyrin template.
      The preparation of supramolecular catalyst systems was also explored using tin
      oxygen interactions. Dihydroxotin(IV) porphyrin and carboxylic phosphorus ligands
      assemble into supramolecular ligands and the phosphorus donor atom coordinates to
      transition metals. The stronger oxygen-tin bond, compared to pyridine-zinc does
      not result in a better performance of the catalyst.

PMID- 17534490
TI  - Influence of the bridging ligand on the substitution behaviour of dinuclear
      Pt(II) complexes. An experimental and theoretical approach.
AB  - A series of dinuclear Pt(II) complexes of the type [Pt2(N,N,N',N'-tetrakis(2
      pyridylmethyl)diamine(H2O)2]4+ were synthesized. Acid-base titrations, and
      concentration and temperature dependent stopped-flow measurements of the reaction
      with chloride were performed to study the thermodynamic and kinetic behaviour of
      the dinuclear bridged complexes. The results indicate that there is a clear
      interaction between the two Pt(II) centres, which becomes weaker as the aliphatic
      chain increases in length. From a certain chain length onwards, the Pt(II)
      centres become independent of each other and exhibit identical thermodynamic and
      kinetic properties. The experimental results are discussed in reference to
      structures obtained by DFT (BP86/LACVP*) calculations.

PMID- 17534492
TI  - Rigid bis-zinc(II) salphen building blocks for the formation of template-assisted
      bidentate ligands and their application in catalysis.
AB  - The template-induced formation of chelating bidentate ligands by the selective
      self-assembly of two monodentate pyridyl phosphorus ligands on a rigid bis
      zinc(II) salphen template with two identical binding sites was studied. Using UV
      vis, NMR-spectroscopy and X-ray analysis the formed structures were unambiguously
      proven. The application of these templated bidentate ligands in transition metal
      catalysis showed, in most cases, typical bidentate character. Compared to
      previous work based on a more flexible bis-zinc(II) porphyrin template, the
      current catalytic data suggest that the rigidity of the template is not an
      important factor for the improvement of the regio- and enantioselectivity under
      the applied reaction conditions.

PMID- 17534493
TI  - Mechanistic studies on oxidation of nitrite by a {Mn3O4}4+ core in aqueous acidic
      media.
AB  - [MnIV3(micro-O)4(phen)4(H2O)2]4+ (, phen=1,10-phenanthroline) equilibrates with
      its conjugate base [Mn3(micro-O)4(phen)4(H2O)(OH)]3+ in aqueous solution. Among
      the several synthetic multinuclear oxo- and/or carboxylato bridged manganese
      complexes known to date containing metal-bound water, to the best of our
      knowledge, only deprotonates (right harpoon over left harpoon+H+, pKa=4.00 (+/
      0.15) at 25.0 degrees C, I=1.0 M, maintained with NaNO3) at physiological pH. An
      aqueous solution of quantitatively oxidises NIII (HNO2 and NO2-) to NO3- within
      pH 2.3-4.1, the end manganese state being MnII. Both and are reactive oxidants in
      the title redox. In contrast to a common observation that anions react quicker
      than their conjugate acids in reducing metal centred oxidants, HNO2 reacts faster
      than NO2- in reducing or . The observed rates of nitrite oxidation do not depend
      on the variation of 1,10-phenanthroline content of the solution indicating that
      the MnIV-bound phen ligands do not dissociate in solution under experimental
      conditions. Also, there was no kinetic evidence for any kind of pre-equilibrium
      replacement of MnIV-bound water by nitrite prior to electron transfer which
      indicates the substitution-inert nature of the MnIV-bound waters and the 1,10
      phenanthroline ligands. The MnIV3 to MnII transition in the present observation
      proceeds through the intermediate generation of the spectrally characterised
      mixed-valent MnIIIMnIV dimer that quickly produces MnII. The reaction rates are
      substantially lowered when solvent H2O is replaced by D2O and a rate determining
      1e, 1H+ electroprotic mechanism is proposed.

PMID- 17534494
TI  - A deliberate approach for the syntheses of heterometallic supramolecules
      containing dimolybdenum Mo(2)4+ species coordinated to other metal units.
AB  - Two compounds with quadruply bonded Mo2(4+) species having isonicotinate ligands
      bound through the carboxylate group have been designed to act as anglers by
      luring metal-containing Lewis acids to bind to the N-pyridyl group. The corner
      pieces are Mo2(DAniF)3(O2CC5H4N) and cis-Mo2(DAniF)2(O2CC5H4N)2, DAniF=N,N'-di(p
      anisyl)formamidinate. The heterometallic molecular rods -Ni(acac)2-and
      Rh2(O2CCH3)4- were made by reaction of with Ni(acac)2 and the metal-metal bonded
      species Rh2(O2CCH3)4, respectively. In these compounds either a mononuclear or a
      dinuclear species are sandwiched between two molecules of . The cisoid compound
      has been employed for the synthesis of a molecular rhombus, [-Zn(Cl2)]2. The
      successful syntheses and isolation of show that the use of corner pieces with
      angler groups is an excellent approach for making heterometallic supramolecular
      compounds having a combination of metal-metal bonded units and other metal
      species.

PMID- 17534495
TI  - Synthesis, spectroscopic characterization, axial base coordination equilibrium
      and photolytic kinetics studies of a new coenzyme B12 analogue-3'-deoxy-2',3'
      anhydrothymidylcobalamin.
AB  - A new coenzyme B12 (AdoCbl) analogue, 3'-deoxy-2',3'-didehydrothymidylcobalamin
      (2',3'-anThyCbl) was prepared by the reaction of 5'-iodo-3'-deoxy-2',3'
      dihydrothmidine with reduced B12a, and characterized by UV-Vis, CD, ESI-MS and
      NMR spectroscopies. Its axial base (dbzm) coordination equilibria with pH's and
      temperatures were investigated and showed similar features to those of coenzyme
      B12. Photolytic dynamics studies under homolytic and heterolytic conditions
      demonstrated that the Co-C bond of the analogue is slightly more photolabile
      relative to coenzyme B12.

PMID- 17534496
TI  - Cascading pericyclic reactions: building complex carbon frameworks for natural
      product synthesis.
AB  - Tandem reactions have emerged as powerful strategies to synthesize complex
      structures, in particular, processes involving pericyclic reactions. This article
      describes recent advancement by our group in the development of novel tandem
      pericyclic reactions aimed at constructing diterpene frameworks.

PMID- 17534497
TI  - Significant enhancement on selectivity in silica supported sulfonic acids
      catalyzed reactions.
AB  - Thanks to strong hydrophilic interactions between reaction products and the
      catalyst surface, mesoporous silica supported sulfonic sites were found to be
      much more selective than homogeneous and common solid acid catalysts.

PMID- 17534498
TI  - Assembly of gold rings and chains with pyridyl carboxylate as directional spacer.
AB  - The combinative use of Au(I), a skeletally flexible diphosphine and a
      bifunctional spacer of pyridyl carboxylate with tunable directional and donor
      properties has resulted in a series of structurally distinctive ensembles and
      Au(2) metalloligands with O-donicity.

PMID- 17534499
TI  - Organocatalytic asymmetric Friedel-Crafts alkylation/cascade reactions of
      naphthols and nitroolefins.
AB  - The asymmetric Michael-type Friedel-Crafts reaction of naphthols and nitroolefins
      promoted by bifunctional thiourea-tertiary amine organocatalysts (up to 95% ee)
      was investigated; on simply extending the reaction time further cascade reactions
      could occur to generate enantiopure dimeric tricyclic 1,2-dihydronaphtho[2,1
      b]furanyl-2-hydroxylamine derivatives.

PMID- 17534500
TI  - Computational structure-activity relationships in H2 storage: how placement of N
      atoms affects release temperatures in organic liquid storage materials.
AB  - DFT(B3PW91) calculations show that release of H2 is greatly favored
      thermodynamically in five membered rings over six and by the incorporation of N
      atoms into the rings, either as ring atoms or as ring substituents, particularly
      in 1,3 positions.

PMID- 17534501
TI  - Anion templated surface assembly of a redox-active sensory rotaxane.
AB  - Anion templation is used to assemble novel redox-active bis-ferrocene
      functionalised rotaxane self-assembled monolayers (SAMs) on to gold electrode
      surfaces; after template removal, the unique SAM rotaxane binding domain is
      capable of selectively sensing chloride ions electrochemically.

PMID- 17534502
TI  - A simple fabrication route to a highly transparent super-hydrophobic surface with
      a poly(dimethylsiloxane) coated flexible mold.
AB  - A super-hydrophobic and highly transparent nanostructured film was fabricated via
      imprinting and conformally uniform chemical anchoring of poly(dimethylsiloxane)
      on a controlled nanoscopic dimension.

PMID- 17534503
TI  - Macrocyclic scaffolds derived from p-aminobenzoic acid.
AB  - The regiospecific synthesis of C3 macrocyclic scaffolds possessing multiple
      different functional groups is described.

PMID- 17534504
TI  - Symmetric and asymmetric 13-vertex bimetallacarboranes by polyhedral expansion.
AB  - Symmetric 4,5,2,3-M(2)C(2)B(9) 13-vertex bimetallacarboranes of cobalt and
      ruthenium with 14 skeletal electron pairs are afforded by reduction and
      metallation of 3,1,2-MC(2)B(9) icosahedra; the symmetric species can be converted
      to their asymmetric 4,5,1,6-M(2)C(2)B(9) isomers by heat, but an easier route is
      by thermolysis of the reduced species before metallation.

PMID- 17534505
TI  - Probing the solvent-induced tautomerism of a redox-active ureidopyrimidinone.
AB  - A ferrocene-functionalised ureidopyrimidinone has been synthesised that can
      signal the solvent-induced tautomerism of the dimeric 4[1H]-pyrimidinone form to
      the monomeric 6[1H]-pyrimidinone form.

PMID- 17534506
TI  - A chemoselective approach for the accelerated synthesis of well-defined dendritic
      architectures.
AB  - A chemoselective and layered growth approach has been developed for the synthesis
      of dendrimers, combining Click chemistry with traditional
      esterification/etherification reactions, without the need for activation steps
      and with excellent overall yields.

PMID- 17534507
TI  - Beyond classical coordination: silver-pi interactions in metal dipyrrin
      complexes.
AB  - Homo- and hetero-leptic Zn and Cu complexes of dipyrrin type ligands bearing mono
      and di-cyanophenyl groups when combined with silver cations lead to the
      formation of Ag(I)-C=C double bond interactions unprecedented in the crystalline
      phase.

PMID- 17534508
TI  - Site-selective depurination by a periodate-dependent deoxyribozyme.
AB  - A deoxyribozyme is identified that mediates the site-selective depurination of
      its 5'-terminal guanosine nucleotide using periodate (IO(4)-) as an obligatory
      cofactor.

PMID- 17534509
TI  - b-Bilene to a,c-biladiene transformation during syntheses of isoporphyrins and
      porphyrins.
AB  - Reaction of 1,19-di-unsubstituted b-bilene salts with alpha-ketoesters gives
      isoporphyrins, and eventually porphyrins, by way of an a,c-biladiene salt
      intermediate.

PMID- 17534510
TI  - Ultra-fast hydrothermal synthesis of diastereoselective pure ethenylene-bridged
      periodic mesoporous organosilicas.
AB  - A novel synthesis of diastereoselective pure periodic mesoporous ethenylene
      silicas is presented, using (a) the homemade E-diastereoisomer of
      bis(triethoxysilyl)ethene, (b) a more efficient extraction procedure of the
      template P123 and (c) an ultra-fast synthesis procedure.

PMID- 17534511
TI  - Nucleophilic aromatic substitution using Et3SiH/cat. t-Bu-P4 as a system for
      nucleophile activation.
AB  - A novel type of deprotonative arylation of nucleophiles was conducted using
      Et(3)SiH/cat. t-Bu-P4 and the powerful S(N)Ar reactions of aryl fluorides were
      accomplished using alcohols and malonates as nucleophiles.

PMID- 17534512
TI  - A planar chelating bitriazole N-heterocyclic carbene ligand and its rhodium(III)
      and dirhodium(II) complexes.
AB  - The new ligand bitriazole-2-ylidene (bitz) reliably chelates to Rh under very
      mild conditions, providing an NHC analogue of 2,2'-dipyridyl ligand.

PMID- 17534513
TI  - Electrochemical conversion of dinitrogen to ammonia mediated by a complex of
      fullerene C60 and gamma-cyclodextrin.
AB  - We report on an electrochemical conversion of N2 to NH3 at ambient pressure and
      60 degrees C, which is mediated by reduced C(60) inside the molecular cavity of
      gamma-cyclodextrin.

PMID- 17534514
TI  - Enhancement of large magnetoresistances in ruthenocuprates by Ta substitution.
AB  - An unexpected enhancement of the large negative magnetoresistance (MR) observed
      in RuSr(2)Nd(0.95)Y(0.15)Ce(0.9)Cu(2)O(10-delta) up to -47% at 4 K and 9 T is
      evidenced upon dilution of the Ru magnetic order by substitution of Ta for Ru;
      this enhancement of -MR scales with the cell volume.

PMID- 17534516
TI  - Electrical properties of 1,4-bis(4-(phenylethynyl)phenylethynyl)benzene and its
      application for organic light emitting diodes.
AB  - We found that a phenylene ethynylene derivative, 1,4-bis(4
      (phenylethynyl)phenylethynyl)benzene (BPPB), provides very high photoluminescence
      efficiency both in solution (Phi(PL) = 95 +/- 3%) and thin films (Phi(PL) = 71 +/
      3%); further, we observed blue electroluminescence (EL) of lambda(EL(max))
      approximately 470 and 510 nm with an external EL efficiency of eta(EL)
      approximately 0.53% and maximum luminance of approximately 70000 cd m(-2) at
      current density of approximately 2 A cm(-2) with BPPB as an emitter; also we
      identified that BPPB functions as a hole transport layer in organic light
      emitting diodes.

PMID- 17534515
TI  - Control of nano-micrometric twist and helical ribbon formation with gemini
      oligoalanine via interpeptidic beta-sheet structure formation.
AB  - Confinement of anionic oligo-alanine peptides at the surfaces of cationic
      membrane by ionic interaction can induce their secondary structure formation;
      such organized peptides reciprocally transfer their chirality to membranes with
      non-chiral amphiphiles and their supramolecular chiral structures can be tuned
      both by peptides and amphiphiles structures.

PMID- 17534517
TI  - Lewis acid-catalyzed formation of indene derivatives via tandem reactions of
      arylacetylenes with the cations generated from 2-silylmethyl cyclopropyl
      carbinols.
AB  - Vicinal silylmethyl-substituted cyclopropyl carbinols undergo tandem
      intermolecular cation-arylacetylene cyclization to generate indene derivatives.

PMID- 17534518
TI  - Stereoselective construction of fluorinated indanone derivatives via a triple
      cascade Lewis acid-catalyzed reaction.
AB  - A one-pot three-component cascade reaction proceeds by way of a Lewis acid
      catalyzed Knoevenagel condensation/Nazarov cyclization/electrophilic fluorination
      sequence to afford fluorinated 1-indanone derivatives in moderate to good yields
      with high diastereoselectivities.

PMID- 17534519
TI  - SUPRAphos-based palladium catalysts for the kinetic resolution of racemic
      cyclohexenyl acetate.
AB  - High-throughput screening of the SUPRAphos library revealed a palladium catalyst
      based on supramolecular ligands that gave fast and highly efficient kinetic
      resolution of cyclohexenyl acetate with an S-value up to 12.

PMID- 17534520
TI  - Magnetic canting or not? Two isomorphous 3D CoII and NiII coordination polymers
      with the rare non-interpenetrated (10,3)-d topological network, showing spin
      canted antiferromagnetism only in the CoII system.
AB  - The in situ solvothermal reaction of 3,4-dicyano-1,2,5-thiadiazole with MCl(2) (M
      = Co, Ni) and NaOH afforded two isomorphous complexes, [M2(L)2(H(2)O)2]n (L =
      2,1,3-thiadiazole-4,5-dicarboxylate), which exhibit a rare non-interpenetrated
      (10,3)-d (utp) network topology and interesting magnetic behaviors: spin-canted
      antiferromagnetism for the Co(II) complex, but simple antiferromagnetic coupling
      for the Ni(II).

PMID- 17534521
TI  - Unprecedented interweaving of single-helical and unequal double-helical chains
      into chiral metal-organic open frameworks with multiwalled tubular structures.
AB  - Two novel chiral metal-organic open frameworks with unprecedented multiwalled
      tubular channels and interweaving of single-helical and unequal double-helical
      units were reported, which possess novel four-connected 4(2)8(3)10 topology and
      represent the first examples of functional metal-organic frameworks based on both
      flexible tripodal and flexible bisdentate ligands.

PMID- 17534522
TI  - Self-assembly and potassium ion triggered disruption of peptide-based soft
      structures.
AB  - This report describes formation of soft vesicular structures by a tetrapeptide
      and its disruption triggered by potassium ions.

PMID- 17534523
TI  - Sugar sensing based on induced pH changes.
AB  - A sensory assembly consisting of a pH sensitive NIR dye and an arylboronic acid
      shows ratiometric absorption changes with increased fluorescence intensity upon
      addition of sugar in aqueous media; this demonstrates a new signal transduction
      mechanism for the detection of sugar based on pH changes induced in the
      microenvironment of the sensory assembly.

PMID- 17534526
TI  - The Janus nature of heme.

PMID- 17534527
TI  - Heme and virulence: how bacterial pathogens regulate, transport and utilize heme.

PMID- 17534528
TI  - Structural modelling of metal ion binding to human haemopexin.

PMID- 17534529
TI  - Reactivity patterns of cytochrome P450 enzymes: multifunctionality of the active
      species, and the two states-two oxidants conundrum.

PMID- 17534530
TI  - Structure and catalytic mechanism of heme oxygenase.

PMID- 17534531
TI  - Heme to protein linkages in mammalian peroxidases: impact on spectroscopic, redox
      and catalytic properties.

PMID- 17534532
TI  - Variations on a (t)heme--novel mechanisms, redox partners and catalytic functions
      in the cytochrome P450 superfamily.

PMID- 17534534
TI  - Diversity and conservation of interactions for binding heme in b-type heme
      proteins.

PMID- 17534533
TI  - Spectroscopic characterization of heme iron-nitrosyl species and their role in NO
      reductase mechanisms in diiron proteins.

PMID- 17534535
TI  - Properties of an unusual heme cofactor in PLP-dependent cystathionine beta
      synthase.

PMID- 17534537
TI  - Searching for genes underlying susceptibility to osteoporotic fracture: current
      progress and future prospect.
AB  - INTRODUCTION: Osteoporotic fracture (OF) is a public health problem. It is a
      common practice in the genetics of osteoporosis that bone mineral density (BMD)
      was studied as a major surrogate phenotype in gene search for risk of OF (ROF)
      because of their high phenotypic correlation. However, some studies indicate that
      the genetic correlation between BMD and ROF is very low. This implies that most
      genes found important for BMD may not be relevant to ROF. Ideally, employing OF
      per se as a direct study phenotype can directly find the relevant genes
      underlying ROF. EVIDENCE: Here, we summarized some evidence supporting ROF under
      moderate genetic control, and the current progress of molecular genetic studies
      employing OF as the direct study phenotype, then give our consideration on the
      future prospects in the genetics of ROF.

PMID- 17534538
TI  - Population-based reference values for bone mineral density in young men.
AB  - Population-based reference values for peak bone mass density in Danish men. BMD
      of total hip (1.078 +/- 0,14 g/cm2) differed significantly from values from
      National Health and Nutrition Examination Survey III and of total lumbar spine
      ((1.073 +/- 0.125 g/cm2) differed significantly from Hologic values.
      INTRODUCTION: Geographic, ethnic, and socio-economic factors are known to affect
      bone mineral density (BMD) and peak bone mass significantly. Reference values for
      male peak bone mass are scarce, and the diagnosis of male osteoporosis often
      relies on values provided by producers of dual-energy X-ray absorptiometry (DXA)
      equipment. METHODS: The aim of the present study was 1) to establish population
      based reference values for BMD in young men and 2) to study subgroups based on
      variables with suspected impact on bone metabolism. We included 783 young
      Caucasian men aged 20 to 30 years in the Odense Androgen Study (OAS). RESULTS:
      Peak BMD was attained within the third decade. Obesity (BMI > 30 kg/m2) was
      associated with higher BMD. Abuse of anabolic steroids as well as chronic illness
      was associated with lower BMD. Our population-based reference values for BMD of
      the total hip (1.078 +/- 0.14 g/cm2) differed significantly from published values
      from National Health and Nutrition Examination Survey III for non-Hispanic white
      men, while BMD of total lumbar spine (1.073 +/- 0.125 g/cm2) differed
      significantly from Hologic reference values. CONCLUSIONS: Locally derived
      reference values are important to avoid false positive or false negative findings
      during work-up in patients evaluated for osteoporosis.

PMID- 17534539
TI  - Hypocalcemia and parathyroid hormone assay.

PMID- 17534541
TI  - Effects of warm water sitz bath on symptoms in post-anal sphincterotomy in
      chronic anal fissure--a randomized and controlled study.
AB  - BACKGROUND: Sitz bath is frequently recommended by physicians for a variety of
      anal disorders including anal fissure. The aim of the present study was to
      determine whether sitz bath does have any therapeutic properties improving upon a
      patient's postoperative symptoms after a closed lateral sphincterotomy. MATERIALS
      AND METHODS: Forty-six patients were randomly assigned to receive analgesics and
      fiber supplement alone (control patients) or a twice-daily sitz bath along with
      identical fiber and analgesics (sitz bath group). A 24-h pain score--post
      defecation anal burning and symptom improvement--was evaluated on a visual analog
      scale (VAS). RESULTS: The groups were equally matched for age, gender
      distribution, and duration of disease. No significant difference in mean pain
      score between groups (p = 0.284) was noticed after one week. However, the
      patients from the control group experienced significant anal burning compared
      with patients from sitz bath group (p < 0.0001). The improvement score was higher
      in the sitz bath group when compared with the control group; however, it did not
      reached a statistically significant level. CONCLUSIONS: Patients after
      sphincterotomy for anal fissure receiving sitz bath experienced similar levels of
      pain when compared with those not receiving sitz bath. However, they reported a
      significant relief in anal burning and a marginally better satisfaction score and
      no reported adverse side effects.

PMID- 17534542
TI  - Prognosis and prognostic factors of follicular carcinoma in Japan: importance of
      postoperative pathological examination.
AB  - BACKGROUND: Follicular carcinoma is known to show a worse prognosis than
      papillary carcinoma because of distant metastasis in higher incidence. However,
      few studies have been published regarding the prognosis of follicular carcinoma
      patients in Japan, which prompted us to investigate this issue. METHODS: We
      examined the prognosis and whether and how various clinicopathological features
      have affected disease-free survival (DFS) and cause-specific survival (CSS) of
      334 patients who underwent initial surgery for follicular carcinoma. RESULTS: In
      18 patients (5.4%), curative surgery could not be achieved because of distant
      metastasis at surgery in 17 patients and local extension in 1 patient. For 316
      patients who underwent curative surgery, 5-year and 10-year DFS rates were 88.4%
      and 75.3%, respectively. Poorly differentiated carcinoma and widely invasive
      carcinoma, together with some conventional prognostic factors, predicted poorer
      DFS of patients. On multivariate analysis, poorly differentiated carcinoma was an
      independent prognostic factor for DFS. The 5-year and 10-year CSS rates for these
      334 patients were 96.4% and 90.4%, respectively. Curative surgery and poorly
      differentiated carcinoma were recognized as independent prognostic factors.
      CONCLUSIONS: We can hypothesize that follicular carcinoma in Japan is generally a
      nonaggressive disease with a good prognosis. However, because poorly
      differentiated or widely invasive carcinomas showed a worse prognosis,
      postoperative pathological examination is important in predicting patient
      prognosis.

PMID- 17534543
TI  - The influence of high serum testosterone levels on the long-term prognosis in
      male patients undergoing hepatectomy for early stage hepatocellular carcinoma
      without vascular invasion.
AB  - BACKGROUND: The influence of high serum testosterone levels on the long-term
      prognosis in male patients undergoing hepatectomy for hepatocellular carcinoma
      (HCC) remains to be fully elucidated. The aim of the present study was to conduct
      a retrospective investigation of the impact of high serum testosterone levels on
      the risk of tumor recurrence and long-term prognosis in male patients undergoing
      hepatectomy for early stage HCC without vascular invasion. METHODS: Between
      August 1995 and March 1999, 42 male patients undergoing curative hepatectomy for
      HCC of tumor-node-metastasis (TNM) stages I and II without vascular invasion were
      enrolled in the study. Preoperative serum testosterone concentration was
      measured. The clinicopathological features, tumor recurrence rates, and 5-year
      disease-free and actuarial survival after hepatectomy were compared between the
      patients with serum testosterone levels in the upper half (group I, n = 21) and
      the patients in the lower half (group II, n = 21). RESULTS: The background and
      clinicopathological features did not differ significantly between groups I and
      group II. All survivors were followed up for more than 5 years. Until March 2005,
      patients in group I, with serum testosterone levels in the upper half, had a
      significantly higher percentage of 5-year tumor recurrence than group II, with
      lower testosterone levels (76.2% versus 28.6%; p < 0.005). The patients in group
      I also had a significantly inferior 5-year disease-free (p < 0.01) and actuarial
      (p < 0.05) survival rates than patients in group II. CONCLUSIONS: Male patients
      with high serum testosterone levels undergoing hepatectomy for early stage HCC
      without vascular invasion have significantly higher 5-year tumor recurrence rates
      and an inferior long-term prognosis than patients with low testosterone levels.
      These findings signal a strategy of adjuvant anti-androgen treatment selectively
      targeted for the male patients with high serum testosterone levels after
      hepatectomy for early stage HCC without vascular invasion to achieve better long
      term outcome.

PMID- 17534544
TI  - Serum levels of uric acid and diabetes mellitus influence survival after surgery
      for primary hyperparathyroidism: a prospective cohort study.
AB  - BACKGROUND: Primary hyperparathyroidism (pHPT) is associated with an increased
      mortality attributable to cardiovascular disease (CVD), suggested to be
      alleviated by surgery. The exact mechanism of the beneficial influence of
      parathyroidectomy on survival is unknown. Furthermore, studies suggest that there
      is no increased mortality compared to the mortality rate in the general
      population during recent years. This study therefore investigated relative
      survival (RS), as well overall mortality associated with the clinical and
      biochemical variables in patients undergoing operation for sporadic pHPT.
      Furthermore, the influence of surgery on biochemical variables associated with
      pHPT was analyzed. METHODS: A group of 323 patients with sporadic pHPT operated
      between September 1989 and July 2003 were followed from surgery over a 10-year
      period. The median and mean follow-up time was 69 and 70 months, respectively
      (range: 1-120 months). Relative survival (RS) was calculated, and the impact of
      clinical and biochemical variables on overall death were evaluated. RESULTS:
      Postoperatively, serum levels of triglycerides and uric acid decreased. Glucose
      levels and glomerular filtration rate remained unchanged. A decreased RS was
      evident during the latter part of the 10 year follow-up period. In the
      multivariate Cox-analysis, diabetes mellitus (hazard ratio [HR] = 2.8, 95%;
      confidence interval [CI] 1.2-6.7), and the combination of an increased level of
      serum uric acid and cardiovascular disease (CVD) (HR = 8.6, 95%; CI 1.5-49.7) was
      associated with a higher mortality. The increased risk of death was evident for
      patients with persistently increased levels of uric acid postoperatively (HR =
      4.8, 95%; CI = 1.4-16.01). CONCLUSIONS: Patients undergoing operation for pHPT
      had a decreased RS during a 10-year follow-up compared to the general population.
      This decrease in RS is associated with diabetes mellitus and increased levels of
      uric acid pre-and postoperatively.

PMID- 17534545
TI  - Synchronous resection of colorectal primary cancer and liver metastases.
AB  - BACKGROUND: Patients with synchronous colorectal liver metastases are thought to
      have a less favorable prognosis than those with colorectal cancer alone. Surgical
      treatment options are controversial, be it synchronous resection or staged
      resection. This study compared the clinical, perioperative, disease-free survival
      (DFS), and overall survival (OS) results of patients undergoing synchronous
      resection versus staged resection. METHODS: An observational cohort study of 103
      patients with synchronous colorectal liver metastases was performed. All data
      were collected prospectively. Clinical, perioperative, DFS, and OS results of
      patients undergoing synchronous resection (group I, n = 73) and staged resection
      (group II, n = 30) were compared. RESULTS: More patients in group I had poorly
      differentiated colorectal cancer, bilobar liver metastases, more than three liver
      metastases, < or =4 cm liver metastases, and shorter hospital stays than patients
      in group II. There were no significant statistically differences in DFS and OS
      between the two groups. The median DFS of groups I and II were 28 and 26 months,
      respectively (p = 0.585). The median OS of groups I and II were 37 and 36 months,
      respectively (p = 0.900). CONCLUSIONS: Synchronous resection achieved DFSs and
      OSs similar to those seen after staged resection while avoiding a second major
      operation.

PMID- 17534546
TI  - Strength of esophageal closure techniques with and without tissue reinforcement.
AB  - OBJECTIVES: The purpose of this study was to investigate the effects of
      esophagotomy closure techniques on the esophageal bursting pressure. MATERIALS
      AND METHODS: Altogether, 122 freshly dead sheep esophagi received from the local
      slaughterhouse were prepared for manual closure. After esophagotomy, the
      specimens were divided into four groups. An interrupted mucosal suture pattern (n
      = 30), an interrupted mucosal-submucosal suture pattern (n = 30), an interrupted
      mucosal-submucosal + over-over continuous muscular suture pattern (n = 32), and
      an interrupted mucosal-submucosal + reinforcement with a diaphragmatic part with
      full-thickness interrupted U suture pattern (n = 30) were used for esophagotomy
      closure; 4-0 silk was used in all specimens. Bursting pressures were measured
      with a sphygmomanometer. RESULTS: We found a statistically significant difference
      among the bursting pressures of all groups (p < 0.001). The bursting pressure
      values gradually increased from group 1 to group 4 (47.6 +/- 22.7, 86.2 +/- 49.5,
      185.4 +/- 53.5, and 226.8 +/- 62.4 mmHg, respectively). Reinforcing the
      esophageal suture line with tissue significantly increased the bursting pressure
      compared to the other groups. CONCLUSIONS: Each layer of the esophagus
      significantly contributes to strengthening esophageal wall tension with primary
      esophageal closure, and reinforcement of the esophageal suture with tissue
      provides an additional significant increase in the bursting pressure of the
      esophagus.

PMID- 17534547
TI  - Tumor localization for laparoscopic colorectal surgery.
AB  - BACKGROUND: Because palpating colonic tumors during laparoscopy is impossible,
      the precise location of a tumor must be identified before operation. The aim of
      this study was to evaluate the accuracy of various diagnostic methods that are
      used to localize colorectal tumors and to propose an adequate localization
      protocol for laparoscopic colorectal surgery. METHODS: A total of 310 patients
      underwent laparoscopy-assisted colectomy between April 2000 and March 2006. We
      investigated if the locations of the tumors that were estimated preoperatively
      were consistent with the actual locations according to the operation. RESULTS:
      All the tumors were correctly localized and resected. Altogether, 203 patients
      had complete endoscopic reports available. Colonoscopy was inaccurate for tumor
      localization in 23 cases (11.3%). In total, 104 patients (33.5%) underwent barium
      enema; five tumors (4.8%) were not visualized, and three tumors were incorrectly
      localized. Another group of 94 patients (30.3%) underwent computed tomography
      (CT) colonography, which identified 91 of 94 lesions (96.8%). Finally, 96
      patients (31.0%) underwent endoscopic tattooing; 2 patients (2.1%) did not have
      tattoos visualized laparoscopically and required intraoperative colonoscopy to
      localize their lesions during resection. Dye spillage was found in six patients
      intraoperatively, but only one patient experienced clinical symptoms.
      Intraoperative colonoscopy was performed in four patients; two of the four were
      followed by endoscopic tattooing, and the other two underwent intraoperative
      colonoscopy for localization. All lesions were correctly localized by
      intraoperative colonoscopy. The accuracy of tumor localization was as follows:
      colonoscopy (180/203, 88.7%), barium enema (97/104, 93.3%), CT colonography
      (89/94, 94.7%), endoscopic tattooing (94/96, 97.9%), and intraoperative
      colonoscopy (4/4, 100%). CONCLUSIONS: With a combination of methods, localization
      of tumors for laparoscopic surgery did not seem very different from that during
      open surgery. Preoperative endoscopic tattooing is a safe, highly effective
      method for localization. In the case of tattoo failure, intraoperative
      colonoscopy can be used for accurate localization.

PMID- 17534548
TI  - Lung function after the minimal invasive pectus excavatum repair (Nuss
      procedure).
AB  - BACKGROUND: The Nuss procedure was introduced at our center in 1999. The
      operation was mainly performed for cosmesis. Little information is available
      regarding the influence of this operation on lung function. METHODS: The aim of
      this study, a prospective analysis, was to analyze the effect of the Nuss
      procedure on lung function variables. Between 1999 and 2007 a total of 203
      patients with pectus excavatum were treated with the Nuss procedure, of whom 145
      (104 male, 41 female) were located at Emma Children's Hospital. In the latter
      subset of consecutive patients, static lung function variables [total lung
      capacity (TLC), functional residual capacity (FRC), vital capacity (VC)] and
      dynamic lung function variables [forced expired volume in 1 s (FEV(1)), maximum
      expiratory flow (MEF(50))] were performed using spirometry and body box
      measurements at four time points: prior to operation (T0), 6 months after the
      Nuss procedure (T1, n = 111), prior to removal of the Nuss bar (T2, n = 74), and
      6 months after removal (T3, n = 53). All values were expressed as a percent of
      normal values for sex, age, and height. Results were compared with a paired
      samples t-test, with the level of significance at p = 0.05. RESULTS: At 6 months
      after bar insertion the TLC, FRC, VC, FEV(1), and MEF(50) showed a significant
      increase; and prior to bar removal the FRC and MEF(50) showed significantly
      increased values. At 6 months after Nuss bar removal, none of the lung function
      variables showed any significant change compared to the preoperative values.
      CONCLUSION: After the Nuss procedure for pectus excavatum, there was no
      improvement of pulmonary function, but neither was the patient's pulmonary
      function harmed by resolving a largely cosmetic problem.

PMID- 17534550
TI  - Telesurgery: remote knowledge translation in clinical surgery.
AB  - Dissemination of new surgical knowledge, skills, and techniques across the wide
      spectrum of practicing surgeons in the community is often difficult and slow.
      This is even more problematic in countries such as Canada, where geographic
      distances separate a large portion of community surgeons from the large teaching
      centers. As an example, the penetration of advanced minimally invasive techniques
      in Canada has been severely hampered by the inability to provide adequate
      training opportunities and support for community surgeons, many of whom live in
      remote regions of the country. In an attempt to overcome the barriers that exist,
      the Centre for Minimal Access Surgery (CMAS) at McMaster University has been
      using broadband Internet and telecommunication systems to provide distance
      training and mentoring to community surgeons living in remote northern
      communities of Canada. This article describes our experience with telementoring
      and robot-assisted remote telepresence surgery and assisting, between a teaching
      hospital in Hamilton and two community hospitals in northern Ontario and Quebec.

PMID- 17534551
TI  - Improving outcomes in hernia repair by the use of light meshes.

PMID- 17534553
TI  - Surgical education in the Canadian socialized health care system.

PMID- 17534555
TI  - Reduced neuronal innervation in the distal end of the proximal esophageal atretic
      segment in cases of esophageal atresia with distal tracheoesophageal fistula.
AB  - BACKGROUND: Esophageal dysmotility is a common occurence after surgical repair of
      proximal esophageal atresia (EA) and distal tracheoesophageal fistula (TEF). The
      etiology of this motility disorder, however, remains controversial. Esophageal
      dysmotility also is present in isolated TEF or EA before surgery, suggesting a
      congenital cause. However, there is no information available in the literature
      with regard to the intramural nervous system of the human esophagus in EA-TEF.
      PATIENTS AND METHODS: We examined the distal end of proximal esophageal atretic
      segment of neonates undergoing EA-TEF repair for intrinsic neuronal innervation.
      Using specific antibodies, we studied neuronal markers of specimens from nine
      cases of EA-TEF and 9 cases of normal esophagus by immunohistochemistry using
      neurofilament (NF), synaptophysin (SY), S100, and glial cell line-derived
      neurotrophic factor (GDNF). RESULTS: In the atretic segment, specimens staining
      with hematoxylin and eosin showed that there were marked hypoganglionosis and
      immature ganglion cells in the myenteric plexus. GDNF immunoreactivity in the
      atretic esophagus were markedly reduced in both the muscular layer and myenteric
      plexus. SY and NF-immunorective nerve fibers were distributed throughout the
      myenteric plexus of the normal esophagus, but the scarcity of these
      immunoreactive nerve fibers in the atretic esophagus was apparent. In contrast,
      the density of immunorective nerve fibers for S100 in the myenteric plexus and
      muscular layer was increased in the distal end of the atretic esophagus.
      CONCLUSION: We concluded that the distribution of ganglion cells and some nerve
      fibers in the distal end of the atretic esophageal segment is deficient.
      Inadequate and abnormal neuronal innervation of the esophagus could be related to
      the esophageal dysmotility seen in EA. Because GDNF is a survival factor for
      central and peripheral neurons, defective expression of GDNF could have an
      important role in the defective and/or abnormal neuronal innervation of atretic
      esophageal segment.

PMID- 17534556
TI  - Outcome of adrenalectomy for Cushing's syndrome: experience from a tertiary care
      center.
AB  - Adrenalectomy continues to play an important role in the management of Cushing's
      syndrome (CS). Untreated CS causes considerable physical and mental morbidity and
      mortality. However, little information is available on the effect of
      adrenalectomy in ameliorating functional disabilities in CS patients. Our study
      assesses the long-term outcome of adrenalectomy in patients with CS. This is a
      retrospective analysis of CS patients managed during 1990-2005 at a tertiary care
      center. We analyzed the clinical presentation, endocrine evaluation, and surgical
      management preoperatively and following adrenalectomy. The subjects were 37
      patients with CS (age 24.5 +/- 15 years, range 1-60 years; male:female 1.0:1.2).
      There were various etiologies--unilateral adrenocortical adenoma (n = 11),
      adrenocortical carcinoma (n = 13), pituitary ACTH-secreting adenoma with failed
      transsphenoidal surgery (n = 4), ectopic unidentified ACTH source (n = 7),
      bilateral adrenal macronodular hyperplasia (n = 1), primary pigmented nodular
      adrenal hyperplasia (n = 1) --for which the patients underwent adrenalectomy:
      unilateral (n = 22), bilateral (n = 13), or adrenonephrectomy (n = 2). Two
      patients died during the perioperative period owing to chest infection and
      sepsis. At the median follow-up of 60 months (range 6-144 months), the patients
      exhibit significant persistence of obesity (41%), proximal muscle weakness (44%),
      menstrual irregularity (8%), hypertension (31%), and insulin-dependent diabetes
      (29%). Hirsutism and psychological abnormalities persisted to a lesser extent.
      All patients had biochemical cure of CS following surgery evidenced by the 8 a.m.
      basal cortisol < or = 5 microg/dl. The hypothalamic-pituitary-adrenal axis
      recovered as shown by normalization of the short synacthen-stimulated cortisol
      level (peak level > or = 20 microg/dl) after a median follow-up of 9 months
      (range 6-18 months). Incomplete clinical recovery following adrenalectomy
      emphasizes the need of early recognition and prompt treatment of CS. Surgery for
      adrenocortical adenoma is safe and effective; however, survival of patients with
      CS due to adrenocortical carcinoma remains poor. Bilateral adrenalectomy provides
      early control of hypercortisolism in selected cases of unlocalized ectopic ACTH
      syndrome or failed transsphenoidal surgery. Even though functional recovery is
      incomplete after adrenalectomy, quality of life improves considerably.

PMID- 17534557
TI  - Role of ultrasonography in predicting malignancy in patients with thyroid
      nodules.
AB  - The use of ultrasonography (USG) has become an essential part of endocrine
      surgical practice. We evaluated the value of USG in predicting malignancy of
      thyroid nodules. The accuracy of USG in 857 patients who underwent fine-needle
      aspiration (FNA) with or without surgery was analyzed in a prospective setting.
      The diagnostic accuracy of USG was compared to that of FNA and of combined models
      in 153 operated patients. The malignancy-predicting value of USG in follicular
      neoplasms and its relation to nodule size were also investigated. Sensitivity,
      specificity, and overall accuracy (OA) of USG were 84.9%, 95.5%, and 93.7%,
      respectively. In operated patients, USG had accuracy comparable to that of FNA
      and combined models (sensitivity 93.3%, specificity 90.6%, OA 92.0%) regardless
      of nodule size but showed a significant rate of indeterminate results (29.4%).
      For follicular neoplasms, the sensitivity, specificity, and OA of USG were 100%,
      95.4%, and 96.1%, respectively, with indeterminate results for three malignant
      nodules (42.8%). This acceptable malignancy-predicting value of USG in thyroid
      nodules supports the potential role of USG for predicting malignancy in selected
      patients with thyroid nodules. However, the high rate of indeterminate results
      precludes it from being a standard independent diagnostic method for the present
      time.

PMID- 17534558
TI  - Identification homologous recombination function from haloarchaea plasmid pHH205.
AB  - Homologous recombination (HR) was found to be so frequent in haloarchaea that its
      significance in evolution and diversity of this clade of life might have been
      underestimated. However, so far there has been no report on recombination
      function carried on plasmid. Here we report that a 4.8-kb SnaBI-PvuII digested
      segment from pHH205 might carry such a function. Four constructed plasmids: pUN,
      pUN-205, pUM and pUM-205, with pUN and pUN205 containing Nov(R) gene, pUM and pUM
      205 carrying Mev(R) gene, were used to transform Haloferax volcanii DS52 (radA(
      )). The results showed that only pUN-205 and pUM-205 containing the 4.8-kb SnaBI
      PvuII digested segment from pHH205 were able to shift Nov(R) and Mev(R) gene into
      the chromosome of Haloferax volcanii DS52 through HR, whereas those in pUN and
      pUM could not, which indicated that the segment from pHH205 does contain a
      recombination function.

PMID- 17534559
TI  - A novel ferric reductase purified from Magnetospirillum gryphiswaldense MSR-1.
AB  - A ferric reductase was purified into an electrophoretically homologous state from
      Magnetospirillum gryphiswaldense MSR-1 strain. The enzyme was found within the
      cytoplasm and associated with the cytoplasmic membrane. The molecular weight of
      the purified enzyme was calculated as 16.1 kDa using sodium dodecyl sulfate
      polyacrylamide gel electrophoresis, and was almost identical to that calibrated
      using agarose gel filtration chromatography. It was NADH-dependent and required
      flavin mononucleotide as a cofactor. The optimal reaction temperature and pH
      values were 30 degrees C and 6.5, respectively. The K(m) and Vmax values for
      ferric citrate were 45.1 microM: and 1.216 microM: min(-1), respectively. Though
      ferric reductase activity could be inhibited by Co(2+), Cu(2+), Mn(2+), and
      Zn(2+), even high concentrations of Mg(2+) ions have failed to accomplish such
      enzyme inhibition. Furthermore, the molecular weight, the N-terminal sequence,
      and the activity of ferric reductase from MSR-1 are not matching with the enzyme
      preparation obtained from an analogous strain M. magnetotacticum (MS-1).
      Therefore, it is concluded that the ferric reductase of M. grysphiwaldense and M.
      magnetotacticum strains are two different enzymes.

PMID- 17534560
TI  - Cloning, expression, and enzyme characterization of an acid heat-stable phytase
      from Aspergillus fumigatus WY-2.
AB  - A novel thermostable phytase gene was cloned from Aspergillus fumigatus WY-2. It
      was 1459 bp in size and encoded a polypeptide of 465 amino acids. The gene was
      expressed in Pichia pastoris GS115 as an extracellular enzyme. The expressed
      enzyme was purified to homogeneity and biochemically characterized. The purified
      enzyme had a specific activity of 51 U/mg with an approximate molecular mass of
      88 kDa. The optimum pH and temperature for activity were pH 5.5 and 55 degrees C,
      respectively. After incubation at 90 degrees C for 15 min, it still remained at
      43.7% of the initial activity. The enzyme showed higher affinity for sodium
      phytate than other phosphate conjugates, and the K(m) and K(cat) for sodium
      phytate were 114 microM: and 102 s(-1), respectively. Incubated with pepsin at 37
      degrees C for 2 h at the ratio (pepsin/phytase, wt/wt) of 0.1, it still retained
      90.1% residual activity. These exceptional properties give the newly cloned
      enzyme good potential in animal feed applications.

PMID- 17534561
TI  - Effect of Some nitrosative agents on the growth of vgb-bearing Enterobacter
      aerogenes strains.
AB  - The effect of transnitrosation intermediate between S-nitroso-N-acetylcysteine
      (NACysNO) and cysteine on the growth of vgb-bearing Enterobacter aerogenes was
      investigated using three parameters: the ratio of the specific growth rates, the
      inhibition zone, and alpha-amylase synthesis for the culture exposed to stressors
      to that of the same stressor-free cultures. The effect of NACysNO/cysteine on the
      growth of Enterobacter strains was distinctive as compared with the CysNO,
      NACysNO, and their combination. At a higher concentration (2 mM), the extents of
      inhibition based on the mu(NACysNO/cysteine)/mu(no stress) ratio for these
      cultures were 57%, 62%, and 68% for VHb-expressing, parental, and pUC9-harboring
      cells, respectively. The inhibition caused by 2 mM: NACysNO in the presence of 1
      mM cysteine in all bacterial strains was almost twofold that achieved by NACysNO
      alone. Based on the diameter of the inhibition zone and alpha-amylase
      productivity, the four compounds (NACysNO/Cysteine, CysNO, NACysNO, and their
      combinations) affected the E. aerogenes strains in a concentration-dependent and
      negative manner. This negative effect was lower in vgb-bearing than vgb-lacking
      strains. Thus, sulfur-to-sulfur transnitrosation was an efficient NO release and
      significantly (P < 0.05) affects the growth of Enterobacter strains, to a lesser
      extent in vgb-bearing strains.

PMID- 17534562
TI  - Site-directed mutagenesis of Aeromonas hydrophila enoyl coenzyme A hydratase
      enhancing 3-hydroxyhexanoate fractions of poly(3-hydroxybutyrate-co-3
      hydroxyhexanoate).
AB  - The aim of this study is to enhance 3-hydroxyhexanoate (3HHx) fractions of poly(3
      hydroxybutyrate-co-3-hydroxyhexanoate), abbreviated as PHBHHx, through site
      directed mutagenesis of Aeromonas hydrophila enoyl Coenzyme A hydratase
      (PhaJ(Ah)). Two amino acids (Leu-65 and Val-130) were selected as a
      substitutional site based on the structural information of PhaJ(Ah). The purified
      proteins from the wild-type enzyme and mutants were used to determine hydratase
      activities. Hydratase activities of four single-mutation enzymes were similar to
      those of the wild type PhaJ(Ah), while hydratase activities of two double
      mutation enzymes were much lower. In addition, the mutated phaJ (Ah) was
      individually co-transformed into E. coli BL21 (DE3) together with pFH21, which
      carried the PHA synthase (PhaC(Ah)) gene from A. hydrophila. The recombinant E.
      coli harboring plasmid pETJ1 (L65A), pETJ2 (L65V) or plasmid pETJ3 (V130A)
      synthesized the enhanced 3HHx fractions of PHBHHx from dodecanoate, indicating
      that Leu-65 and Val-130 of PhaJ(Ah) play an important role in determining the
      acyl chain length substrate specificity. The mutated PhaJ(Ah) (L65A, L65V, or
      V130A) provided higher 3HHx precursors for PHA synthase, resulting in the
      enhanced 3HHx fractions of PHBHHx. It is possible to change the acyl chain length
      substrate specificity of PhaJ through site-directed mutagenesis and produce
      PHBHHx with a wider range of alterable monomer composition.

PMID- 17534563
TI  - Gene cloning, expression, and substrate specificity of an imidase from the strain
      Pseudomonas putida YZ-26.
AB  - A gene-encoding imidase was isolated from Pseudomonas putdia YZ-26 genomic DNA
      using a combination of polymerase chain reaction and activity screening the
      recombinant. Analysis of the nucleotide sequence revealed that an open reading
      frame (ORF) of 879 bp encoded a protein of 293 amino acids with a calculated
      molecular weight of 33712.6 kDa. The deduced amino-acid sequence showed 78%
      identity with the imidase from Alcaligenes eutrophus 112R4 and 80% identity with
      N-terminal 20 amino-acid imidase from Blastobacter sp. A17p-4. Next, the ORF was
      subcloned into vector pET32a to form recombinant plasmid pEI. The enzyme was
      overexpressed in Escherichia coli and purified to homogeneity by Ni(2+)-NTA
      column, with 75% activity recovery. The subunit molecular mass of the recombinant
      imidase as estimated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis
      was approximately 36 kDa, whereas its functional unit was approximately 141 kDa
      with four identical subunits determined by size-exclusion chromatography. The
      purified enzyme showed the highest activity and affinity toward succinimide, and
      some other substrates, such as dihydrouracil, hydantoin, succinimide, and
      maleimde, were investigated.

PMID- 17534564
TI  - Successful occlusion of a persistent left vertical vein with an Amplatzer
      muscular ventricular septal defect occluder.

PMID- 17534565
TI  - The effects of facilitated primary PCI by guide wire on procedural and clinical
      outcomes in acute ST-segment elevation myocardial infarction.
AB  - BACKGROUND: Reperfusion of the infarct related artery (IRA) prior to PCI is
      prognostically important in patients with acute ST segment elevation myocardial
      infarction (STEMI). Reperfusion is either achieved spontaneously, facilitated by
      GP IIb/ IIIa inhibitors, or mechanically by crossing the guide wire beyond the
      lesion. In order to test the hypothesis that a visible coronary anatomy is
      independently associated with procedural and clinical outcomes, we evaluated the
      frequency and prognostic impact of guide wire facilitated reperfusion of the IRA
      before primary PCI. METHODS AND RESULTS: We enrolled 311 consecutive patients
      with successful primary PCI for STEMI (TIMI grade > or =2 flow) within 12 h after
      onset of symptoms. Among these, 90 patients (28.9%) had a spontaneously
      reperfused IRA on initial angiogram, 56 patients (18.0%) achieved reperfusion
      after crossing of the guide wire, and 165 patients (53.1%) successful reperfusion
      only after PCI. Variables associated with successful guide wire facilitated
      reperfusion were younger age, no history of arterial hypertension, active smoking
      status, negative cardiac troponin T on admission, and an infarct in the territory
      of the right coronary artery. Patients with spontaneous reperfusion or
      reperfusion after crossing of the guide wire required less fluoroscopic time and
      less contrast material during angiography and had higher procedural success rates
      (TIMI grade 3 flow 91.1 vs 79.4%, p=0.048) than patients without initial
      reperfusion. In addition, patients with reperfusion after crossing the lesion
      with the guide wire had lower mortality rates at 30 days (3.6 vs 9.1%) and after
      a median of 16 months (3.6 vs 13.9%, p=0.03) than those with reperfusion after
      PCI. CONCLUSIONS: Reperfusion of an occluded IRA by crossing the guide wire is
      associated with higher procedural success rates and better outcomes. Better
      roadmapping and device selection represent potential reasons but the exact
      mechanism for these benefits is still illusive.

PMID- 17534566
TI  - The Sirolimus-eluting coronary stent in daily routine practice in Germany: trends
      in indications over the years. Results from the prospective multi-centre German
      Cypher Stent Registry.
AB  - BACKGROUND: Drugeluting coronary stents (DES) are increasingly used during
      percutaneous coronary interventions (PCI). Due to limited budgets in Germany, no
      special reimbursement has been given for their use and therefore they were mainly
      used in selected patients. METHODS: In order to determine the change in
      indications in patients treated with a Sirolimus-eluting stent (SES) in daily
      clinical practice between 2002 and 2005, we analysed data from a prospective
      multi-centre DES registry, the German Cypher Stent Registry. RESULTS: From April
      2002 until September 2005, 11 507 patients at 132 hospitals, who received at
      least one SES during their PCI, were included. Between 2002 and 2005, the median
      age of patients increased from 63 years to 66 years (p for trend <0.0001),
      whereas the prevalence of prior coronary bypass surgery (p<0.0001) and prior PCI
      (p<0.001) significantly decreased. Initial presentation of patients was stable
      over time, with a small increase of patients treated for non-ST elevation
      myocardial infarction (p=0.05). We found a significant increase in the treatment
      of complex stenoses (p<0.0001) as well as an increase in the proportion of
      chronic total occlusions (p<0.01). There was a steady increase in the proportion
      of patients treated for de novo lesions (p<0.0001), which was accompanied by a
      relative decrease in the proportion of patients treated for in-stent restenosis
      (p<0.0001). Concerning interventional characteristics a significant increase in
      the length of SES implanted per lesion, the numbers of SES implanted per lesion
      as well as an increase of the proportion of patients treated for more than one
      stenosis during one intervention could be observed (all p<0.0001). There was a
      significant decrease in the use of glycoprotein II b/IIIa antagonists during the
      PCI (2002: 26.5 to 14.2% in 2005, p<0.0001). MACE rates until hospital discharge
      did not change significantly over time. CONCLUSIONS: Between 2002 and 2005 there
      were two trends in the use of SES: a) a significant increase in the use of SES
      for de novo lesions and b) a significant trend to use SES for longer lesions,
      smaller arteries, more complex lesions and more SES per lesion. In summary these
      findings indicate that still SES are mainly used in patients with lesions that
      are at high risk for restenosis.

PMID- 17534567
TI  - Evaluation of hospitals regarding outcomes and baseline risk -- an application to
      percutaneous coronary intervention.
AB  - Monitoring of hospital performance is increasingly used in the process of
      improving the quality of health care. Various approaches to quality assessment
      and publication of the results are discussed. Therefore, a method acceptable for
      clinicians in the hospitals is urgently needed. As the case mix of the patients
      differs considerably across hospitals, any assessment based on outcome measures
      has to be adjusted for the patients' risk profiles. We use a method of
      calculation and presentation that relates the observed complication rate of one
      centre to the mean rate that would be expected for similar patients in the other
      centres. We argue that this procedure might especially meet the demands of
      clinicians in the centres. Data from 44 hospitals in the German Cypher Stent
      Registry are used to exemplify the proposed procedure. RESULTS: A large variation
      in the cumulative incidence of MACE within 6 months (range 0-12.2%) as well as in
      the prevalence of selected risk factors was observed across hospitals. Using a
      logistic prediction model, the differences in risk profiles of the patient
      populations in the centres resulted in a wide range of expected MACE rates (2.55
      5.44%). The outcome of seven centres differed significantly from the expectation.
      CONCLUSION: In comparisons of the outcome quality of hospitals, adjustment for
      the patients' baseline risk by an appropriate method is indispensable.

PMID- 17534568
TI  - Isolated noncompaction of the left ventricular myocardium -- a review of the
      literature two decades after the initial case description.
AB  - Isolated noncompaction of the left ventricular myocardium (INVM), first described
      in 1984, is an unclassified cardiomyopathy and is assumed to occur as an arrest
      of the compaction process during the normal development of the heart. Between
      weeks 5 to 8 of human fetal development, the ventricular myocardium undergoes
      gradual compaction with transformation of the relatively large intertrabecular
      spaces into capillaries while the residual spaces within the trabecular meshwork
      gradually flatten or disappear. In the case of INVM, the spaces within the
      intertrabecular meshwork persist while no other cardiac abnormalities exist.
      Although there is substantial evidence supporting the developmental hypothesis,
      other pathogenetic processes responsible for INVM have been discussed. It can be
      assumed that INVM will be better understood in the future as the molecular
      genetic basis of cardiomyopathies will be further unravelled. Echocardiography
      has been shown to be the method of choice in diagnosis of INVM. The diagnostic
      criteria can be summarized as: 1) appearance of at least four prominent
      trabeculations and deep intertrabecular recesses; 2) appearance of blood flow
      from the ventricular cavity into the intertrabecular recesses as visualized by
      color Doppler imaging; 3) the segments of noncompacted myocardium mainly involve
      the apex and the inferior mid and lateral mid of the left ventricular wall and
      typically show a two-layered structure with an endsystolic ratio greater than two
      between the noncompacted subendocardial layer and the compacted subepicardial
      layer; 4) absence of coexisting cardiac abnormalities. Magnetic resonance imaging
      using modern gradient echo sequences has also been shown to diagnose INVM
      accurately. The clinical presentation of INVM is characterized by a high
      prevalence of heart failure, thromboembolic events and arrhythmias including
      ventricular tachycardia and atrial fibrillation. The establishment of a registry,
      which was initiated by the "Arbeitsgemeinschaft Leitende Kardiologische
      Krankenhausarzte (ALKK)" recently, may provide further clues for diagnosis, risk
      stratification, and management of this disease.

PMID- 17534569
TI  - Mother-and-baby technique for catheterization of the left coronary artery in a
      patient with a huge aneurysm of the ascending aorta.

PMID- 17534571
TI  - Giant dumbbell-shaped middle cranial fossa trigeminal schwannoma with extension
      to the infratemporal and posterior fossae.
AB  - We present a 38-year-old female with a giant dumbbell-shaped trigeminal neurinoma
      originating primarily in the middle cranial fossa, extending to the infratemporal
      and posterior fossae through the foramen ovale and Meckel's cave, respectively.
      Because of the large tumour extension into the Infratemporal Fossa, a combined
      skull base approach (zygomatic infratemporal - transmandibular) was utilised for
      tumour removal, with a subsequent excellent outcome. An extensive literature
      review since 1935, revealed 580 cases of surgically treated trigeminal
      neurinomas. Among these, only three were located in three distinct compartments,
      making this the rarest developmental pattern for trigeminal neurinomas.

PMID- 17534570
TI  - Pulmonary hypertension: current diagnosis and treatment.
AB  - Pulmonary hypertension (PH) is a devastating disease that - if untreated - is
      characterized by a poor prognosis. According to the current classification
      (Venice, 2003), pulmonary arterial hypertension (PAH) is distinguished from other
      forms of PH. Recent advances in drug therapy have led to a dramatic improvement
      of medical care particularly in patients with PAH. Hence, early establishment of
      the diagnosis appears increasingly important. This review article gives an
      overview on the definition, classification, pathophysiology, and clinical
      presentation of various forms of PH. Furthermore, it summarizes the recommended
      diagnostic work-up and the current treatment options particularly in PAH, with
      special emphasis on prostanoids, endothelin receptor antagonists (ERAs), and
      phosphopdiesterase type 5 (PDE5) inhibitors such as sildenafil. Finally, novel
      developments are being discussed which currently represent an exciting field of
      research.

PMID- 17534573
TI  - A novel PEX12 mutation identified as the cause of a peroxisomal biogenesis
      disorder with mild clinical phenotype, mild biochemical abnormalities in
      fibroblasts and a mosaic catalase immunofluorescence pattern, even at 40 degrees
      C.
AB  - Mutations in 12 different PEX genes can cause a generalized peroxisomal
      biogenesis disorder with clinical phenotypes ranging from Zellweger syndrome to
      infantile Refsum disease. To identify the specific PEX gene to be sequenced,
      complementation analysis is first performed in fibroblasts using catalase
      immunofluorescence. A patient with a relatively mild phenotype of infantile
      cholestasis, hypotonia and motor delay had elevated plasma very long-chain fatty
      acids and bile acid precursors, but fibroblast studies revealed normal or only
      mildly abnormal peroxisomal parameters and mosaic catalase immunofluorescence.
      This mosaicism persisted even when the incubation temperature was increased from
      37 degrees C to 40 degrees C, a maneuver previously shown to abolish mosaicism by
      exacerbating peroxisomal dysfunction. As mosaicism precludes complementation
      analysis, a candidate gene approach was employed. After PEX1 sequencing was
      unrewarding, PEX12 sequencing revealed homozygosity for a novel c.102A>T (p.R34S)
      missense mutation affecting a partially conserved residue in the N-terminal
      region important for localization to peroxisomes. Transfection of patient
      fibroblasts with wild-type PEX12 cDNA confirmed that a PEX12 defect was the basis
      for the PBD. Homozygosity for c.102A>T was identified in a second patient of
      similar ethnic origin also presenting with a mild phenotype. PEX12 is a highly
      probable candidate gene for direct sequencing in the context of a mild clinical
      phenotype with mosaicism and minimally abnormal peroxisomal parameters in
      fibroblasts.

PMID- 17534574
TI  - Association analysis of genetic variants in IL23R, ATG16L1 and 5p13.1 loci with
      Crohn's disease in Japanese patients.
AB  - Inflammatory bowel diseases, Crohn's disease (CD) and ulcerative colitis are
      characterised by chronic transmural, segmental and typically granulomatous
      inflammation of the gut. Each has a peak age of onset in the second to fourth
      decades of life and prevalence has been increasing significantly in both Western
      countries and Japan over the last decade, while their pathogenesis remains
      largely unknown. Recently, positive association of CD with the variants in
      interleukin 23 receptor (IL23R), autophagy-related 16-like 1 (ATG16L1) genes and
      chromosome 5p13.1 locus was reported through genome-wide association studies
      which are now recognised as a robust tool for the identification of
      susceptibility genes for complex diseases. To examine an association of reported
      susceptible variants in the three loci with Japanese CD patients, a total of 484
      CD patients and 439 controls were genotyped. No evidence of positive association
      for any of these loci with CD was found in the Japanese population, even after
      clinically stratified subgroups of CD were used. Our result revealed a distinct
      ethnic difference of genetic background of CD that we reported previously in
      other genes between Japanese and Caucasian populations. Further genetic studies
      are required to confirm our findings with ethnically divergent populations.

PMID- 17534575
TI  - Tethered polyelectrolytes under the action of an electrical field: a molecular
      dynamics study.
AB  - For a polyelectrolyte undergoing electrophoretic motion, it is predicted (D.
      Long, J.L. Viovy, A. Ajdari, Phys. Rev. Lett. 76, 3858 (1996); D. Long, A.
      Ajdari, Electrophoresis 17, 1161 (1996)) that the mechanical force necessary to
      stall the molecule is substantially smaller than the sum of electrical forces
      applied on all monomers. In fact, it should be proportional to its hydrodynamic
      friction coefficient and therefore to the size of its conformation. In our work
      we examine this prediction using coarse-grained molecular-dynamics simulations in
      which we explicitly include the polymer, the solvent, the counterions and salt.
      The electrophoretic mobility of polyelectrolytes is evaluated, the mechanical
      force necessary to keep the molecules tethered is measured and the resulting
      anisotropic polymer conformations are observed and quantified. Our results
      corroborate Long et al.'s prediction.

PMID- 17534576
TI  - Targeting telomerase activity by BIBR1532 as a therapeutic approach in germ cell
      tumors.
AB  - Germ cell tumors (GCT) possess a high activity of telomerase, a ribonucleoprotein
      complex compensating the erosion of telomeres during cell division by adding
      TTAGGG-repeats to the telomeric ends of chromosomes. Cisplatin, the most
      important drug in the treatment of GCT, preferentially acts on G-rich regions
      like telomeres. Inhibiting telomerase in tumors can result in telomere shortening
      and senescence and could increase the efficacy of chemotherapy in refractory
      patients. The study evaluated the promise of the small molecule telomerase
      inhibitor BIBR1532 as single agent and assessed a possible synergism with
      cisplatin in a preclinical model of GCT.GCT-derived cell line 2102EP was cultured
      with or without 10 microM of BIBR1532. Cell expansion was quantified in
      population doublings (PD). Telomere length was analyzed by fluorescence in situ
      hybridization and flow cytometry (flow-FISH). The sensitivity of the cells
      towards cisplatin was determined by MTT-assay. Telomerase activity was assessed
      by TRAP assay. After 300 PD, telomere length diminished from 18.5 kb +/- 0.59 kb
      to 8.9 +/- 0.1 kb in BIBR1532 treated 2102 EP cells as compared to 14.5 +/- 0.0
      kb in untreated control cells. Treated cells did not show altered growth kinetics
      compared to untreated counterparts. Despite effective shortening of telomeres,
      the sensitivity of the treated cells towards cisplatin did not increase.
      Concomitant treatment with BIBR1532 and cisplatin did not result in accelerated
      telomere shortening. Telomere length can be shortened significantly by telomerase
      inhibition in GCT cell line models. However, possibly in view of their extensive
      telomere "reserve," telomerase inhibition did neither result in increased
      sensitivity of 2102 EP cells to cisplatin nor did co-treated cells show
      accelerated telomere shortening.

PMID- 17534578
TI  - Do we need whole brain irradiation in multifocal or multicentric high-grade
      cerebral gliomas? Review of cases and the literature.

PMID- 17534577
TI  - In vitro chemosensitivity of freshly explanted tumor cells to pemetrexed is
      correlated with target gene expression.
AB  - AIM OF THE STUDY: mRNA expression of genes involved in the mechanism of action of
      pemetrexed was correlated with in vitro chemosensitivity of freshly explanted
      human tumor specimens. EXPERIMENTAL DESIGN: Chemosensitivity to pemetrexed was
      studied in soft-agar. Multiplex rtPCR experiments for reduced folate carrier
      (RFC), folate receptor-alpha (FR-alpha), folylpolyglutamate synthetase (FPGS),
      thymidylate synthase (TS), dihydrofolate reductase (DHFR), glycinamide
      ribonucleotide formyl transferase (GARFT), mrp4, and mrp5 were performed in
      parallel. Correlations, threshold optimization, sensitivity, specificity, and
      efficiency were analyzed using the appropriate statistical methodologies.
      RESULTS: In 61 samples, low levels of TS, GARFT, DHFR, and mrp4 gene expression
      significantly correlated with chemosensitivity to pemetrexed. Optimization
      analyses demonstrated threshold values of 144 copies for TS and six copies for
      mrp4 relative to 10(4) copies of beta-actin. CONCLUSIONS: These results form a
      rational basis for the design of clinical trials to evaluate the expression of
      these enzymes as predictors for treatment outcome.

PMID- 17534579
TI  - Enhancement of cisplatin efficacy by thalidomide in a 9L rat gliosarcoma model.
AB  - With the aim of improving the treatment of glioblastoma multiforme, we
      investigated the potential of thalidomide to enhance the effectiveness of
      cisplatin chemotherapy in a rat glioma model. Female F344 rats were implanted
      with 9L gliosarcoma tumors either intracranially or subcutaneously and treated
      with 1 mg/kg cisplatin injected i.p. or with 1% thalidomide in the food or with
      these treatments combined. Cisplatin in combination with thalidomide
      significantly reduced both the subcutaneous tumor volume at 30 days to 22 +/- 5%
      (mean +/- SEM, P < 0.001) and the intracranial tumor volume at 18 days to 44 +/-
      15% (P < 0.05) of that with cisplatin alone. Thalidomide selectively increased
      the cisplatin concentration 10-fold in intracranial tumors (P < 0.05) and 2-fold
      in the subcutaneous tumors (P < 0.05) without increasing its concentration in
      major organs including brain and kidney. Cisplatin combined with thalidomide
      caused a significant decrease in vascular endothelial growth factor (VEGF) levels
      by 73% in intracranial tumors (P < 0.05) and by 50% in subcutaneous tumors (P <
      0.05) and caused the level of active hepatic growth factor (a-HGF) to double in
      both the subcutaneous and intracranial tumors (P < 0.05), suggesting this
      treatment altered the vasculature in these tumors. We conclude the increased
      efficacy of cisplatin in the presence of thalidomide was due to the selective
      increase in cisplatin concentration within the tumors and speculate that this is
      the result of thalidomide or the cisplatin/thalidomide combination, selectively
      altering the tumor vasculature. Based on the selective effects of thalidomide on
      tumor cisplatin concentrations and the resulting increase in efficacy,
      thalidomide may also increase the efficacy of other drugs that are presently
      considered ineffective against glioma.

PMID- 17534580
TI  - Valproic acid induces p21 and topoisomerase-II (alpha/beta) expression and
      synergistically enhances etoposide cytotoxicity in human glioblastoma cell lines.
AB  - OBJECT: Etoposide, a topoisomerase-II inhibitor promotes DNA damage and apoptosis
      of cancer cells. In this study, we have examined the ability of the histone
      deacetylase inhibitor, valproic acid (VPA) to modulate gene expression and
      sensitize glioblastoma cell lines to the cytotoxic effects of etoposide in vitro.
      METHODS: The effect of VPA and etoposide alone or a combination of the two drugs
      on the growth of three different glioblastoma cell lines (U87, LN18, and U251)
      were measured by MTT assays. Drug treated cells were analyzed for their cell
      cycle profile, gene expression, differentiation status, and induction of
      apoptosis by flow-cytometry, western blotting, immunofluorescence assays, and
      caspase activity measurements. RESULTS: We observed that while VPA and etoposide
      independently inhibited the growth of U87, U251, and LN18 cells, exposure of
      tumor cells to both drugs significantly enhanced the cytotoxicity of etoposide in
      all cell lines. VPA promoted a G(1) accumulation of U87, while an increase in the
      G(2)/M population of U251 and LN18 cells was observed upon exposure to the drug.
      Treatment with etoposide resulted in a G(2)/M arrest of U87, U251, and LN18
      cells, whereas, exposure to both drugs increased the fraction of cells with a
      G2/M and sub-G1 DNA content. Further, VPA and not etoposide, promoted acetylation
      of histone H4 and induced the expression of the cyclin-dependent kinase inhibitor
      (CDKI), p21/WAF1. VPA also up-regulated the expression of the alpha and beta
      isoforms of topoisomerase-II, as well as the glial differentiation marker, glial
      fibrillary acidic protein. Finally, a significant increase in caspase-3 activity
      and apoptosis was observed in the presence of both VPA and etoposide compared to
      either agent alone. CONCLUSION: Our study demonstrates that VPA sensitizes U87,
      U251, and LN18 cells to the cytotoxic effects of etoposide in vitro by inducing
      differentiation and up-regulating the expression of p21/WAF1 and both isoforms of
      topoisomerase-II.

PMID- 17534581
TI  - A child with raccoon eyes masquerading as trauma.
AB  - Raccoon eyes are easily recognized and generally believed to be a common symptom
      of basal skull fractures. However, it may be a sign of some health threatening
      situations such as amyloidosis, Kaposi's sarcoma, multiple myeloma, and
      neuroblastoma. In this case, we present an infant with the final diagnosis of
      neuroblastoma who presented with raccoon eyes and was initially suspected of
      being a victim of child abuse. The exact diagnosis of this condition is sometimes
      delayed because of the workup for child abuse or trauma as occurred in the
      present case. Consequently, in order to avoid this conflict and possible delay of
      diagnosis and treatment, raccoon eyes should be considered meticulously and one
      should not be prejudiced until he / she reaches the exact diagnosis. We are
      presenting this well-known but interesting case in order to attract attention in
      this important issue once again.

PMID- 17534582
TI  - Expression, purification and characterization of soluble human interleukin-6
      receptor alpha-chain and its mutant protein in Escherichia coli.
AB  - To investigate the function of the N-terminal immunoglobulin (Ig)-like domain of
      the human interleukin-6 receptor alpha-chain (hIL-6R), we constructed a soluble
      human interleukin-6 receptor (shIL-6R) (named EC05, amino acids 20-354) and
      soluble variants of the shIL-6R lacking the Ig-like domain (named EC70, amino
      acids 105-354). The two extracellular portions of hIL-6R were expressed as
      soluble fusion proteins with thioredoxin in Escherichia coli and purified by
      using Ni-NTA agarose. Western blot showed that purified proteins were
      immunoreactive with the antibody against hIL-6R. They also possessed specific
      binding activity with human interleukin-6 (hIL-6) in ELISA analysis.

PMID- 17534583
TI  - Mycoparasitism studies of Trichoderma harzianum strains against Rhizoctonia
      solani: evaluation of coiling and hydrolytic enzyme production.
AB  - The genus Trichoderma is a potential biocontrol agent against several
      phytopathogenic fungi. One parameter for its successful use is an efficient
      coiling process followed by a substantial production of hydrolytic enzymes. The
      interaction between fifteen isolates of Trichoderma harzianum and the soil-borne
      plant pathogen, Rhizoctonia solani, was studied by light microscopy and
      transmission electron microscopy (TEM). Macroscopic observations of fungal growth
      in dual cultures revealed that growth inhibition of the pathogen occurred soon
      after contact with the antagonist. All T. harzianum isolates tested exhibited
      coiling around the hyphae of R. solani. The strains ALL23, ALL40, ALL41, ALL43
      and ALL49 did not differ in coiling frequency and gave equal coiling
      performances. No correlation between coiling frequency and the production of cell
      wall-degrading chitinases, N-acetyl-beta-D-glucosaminidase and beta-1,3
      glucanases, was found.

PMID- 17534584
TI  - Predictors and clinical implications of shivering during therapeutic
      normothermia.
AB  - BACKGROUND: Shivering during induced normothermia (IN) remains a therapeutic
      limitation. We investigated potential risk factors and clinical implications of
      shivering during IN. METHODS: Post hoc analysis was performed on 24 patients
      enrolled in a clinical trial of an automated surface cooling system to achieve
      IN. Hyponatremia was defined as serum levels <136 mmol/L and hypomagnesaemia as
      levels <1.5 mg/dL. Continuous heat energy transfer (kcal/h) was averaged hourly.
      Glasgow Coma Scale (GCS) scores were recorded every 2 h. Shivering status was
      documented hourly. Mixed effects modeling was used to determine clinical measures
      associated with shivering. Generalized estimating equation (GEE) models were used
      to compare baseline-adjusted repeated-measures GCS scores. RESULTS: About of 24
      (39%) patients demonstrated shivering. Shivering was associated with men (67% vs.
      21%, P = 0.03), hyponatremia (44% vs. 7%, P = 0.03), and hypomagnesaemia (56% vs.
      7%, P = 0.02). The average kcal/h (158 +/- 645 kcal/h vs. 493 +/- 645 kcal/h, P =
      0.03) was greater in shivering patients. Shivering was positively associated with
      increases in heart rate (P < 0.001), respiratory rate (P < 0.001), and kcal/h (P
      < 0.001). Non-shivering patients showed a greater increase from baseline GCS
      (GEE, P = 0.02) at 24 h. No differences in sedative doses or fever burden were
      noted between shiverers and non-shiverers. CONCLUSIONS: Men, hyponatremia, and
      hypomagnesaemia may predispose febrile patients treated with IN to shivering.
      Shivering dramatically increases the amount of heat transfer required to maintain
      normothermia, and may be associated with adverse effects on level of
      consciousness.

PMID- 17534585
TI  - [Minimally invasive surgery and maximally dominant economy. Are they
      reconcilable?].

PMID- 17534586
TI  - [Are there technological advances in minimally invasive surgery and who will pay
      them?].
AB  - The successful development of minimally invasive surgery would have been
      inconceivable without continuous advances in medical technology. The users, i.e.
      the surgeons, however, only accepted innovations with a clear-cut positive impact
      on clinical care. Accordingly, the expected exponential rise in costs could be
      avoided. The imbalance in cost/benefit aspects between the deliverers of medical
      care on one hand, and the patients, the insurance companies and the employers on
      the other is critical. In addition, further innovations are to be expected. This
      will not be possible without increasing costs, but there are good reasons to
      assume that expenses will rise only moderately. Each modern society is able (and
      obliged) to afford a certain amount of medical progress in order to maintain a
      high level of medical care and economic strength.

PMID- 17534587
TI  - [Diving for children: the 3rd Heidelberg Symposium on diving medicine].

PMID- 17534588
TI  - Physicochemical and physiological basis of dichromatic colour.
AB  - Out of three perceptual characteristics of the colour of any substance, the hue
      depends mostly on the spectral properties of a substance, while the brightness
      and saturation depend also on the concentration of a substance and its thickness.
      Here, we report that evident change of the hue of the colour (i.e., from green to
      red) is due to a change in concentration or the thickness of a layer in some
      exceptional substances such as pumpkin seed oil or an aqueous solution of
      bromophenol blue. In some regions of Central Europe, salad dressing is made
      preferably with the pumpkin seed oil, which has a strong characteristic nut-like
      taste and remarkable properties of the colour: it appears red in a bottle, but
      green when served as a salad dressing. The colour of the pumpkin seed oil was
      previously described as brownish yellow, dark green, dark green to red ochre or
      dark reddish brown to light yellow green. We elucidated the physicochemical and
      physiological basis of such dichromatism by Beer-Lambert law and by the
      characteristics of human colour perception. Our concept was corroborated by the
      outcome of calculations of colour from spectral properties using colour matching
      functions. We found that dichromatism is observed if the absorption spectrum of
      any substance has at least two local minima: one wide but shallow and one narrow
      but deep local minimum.

PMID- 17534589
TI  - Experimental evidence for species-specific habitat preferences in two flycatcher
      species in their hybrid zone.
AB  - Hybrid zones are often found in areas where the environmental characteristics of
      native habitat of both parental species meet. One of the plausible mechanisms
      that maintain species distinctiveness, or limit hybridization, is the existence
      of local species-specific preferences for the natal habitat type. We evaluated
      this hypothesis for two passerine bird species, the pied Ficedula hypoleuca and
      collared flycatcher F. albicollis, in their narrow hybrid zone in Central Europe.
      Both species have quite distinct habitat distributions, and they have also been
      reported to differ in their foraging niches. In a series of aviary experiments,
      we demonstrated that both species show distinct preferences for trees from their
      native area. The pied flycatcher preferred coniferous vegetation, while the
      collared flycatcher favored deciduous vegetation. In addition, both species
      differed in foraging substrate preferences. The pied flycatcher preferred to
      forage in the lower strata on the ground than the canopy, whereas the collared
      flycatcher foraged more at the canopy level. Both males and females of each
      species were highly consistent in their preference patterns. Due to the
      widespread nature of hybrid zones as places with transitional habitat features
      and the well-known habitat tight associations of various animal taxa with
      particular habitat types, we propose that habitat preferences might be an
      important and common mechanism that enhances the formation of conspecific pairs.

PMID- 17534590
TI  - Prey detection without successful capture affects spider's orb-web building
      behaviour.
AB  - Animals obtain information from past foraging experience to adjust their foraging
      activity according to their environment. The ability of spiders to obtain
      information from unsuccessful predation experiences was investigated by examining
      the effects on web building, a significant foraging investment, of prey detection
      without successful capture in the orb-web spider Cyclosa octotuberculata. Four
      treatments were employed: (1) successful capture and feeding: one syrphid fly was
      allowed to be captured and consumed by the spider on the web; (2) single prey
      item detection: a syrphid fly was placed on the web to lure the spider, but was
      removed before capture; (3) five prey-item detection: above prey-item detection
      stimulus was given five times; and, (4) control: neither prey nor feeding on the
      web. While control spiders decreased the total thread length and capture area of
      their webs, prey-item detection spiders in both conditions increased them,
      indicating that the spider obtained information from unsuccessful predation
      experience to adjust their foraging investment. The fed spiders exhibited a
      significantly greater increase than the prey-detection-only spiders, suggesting
      that prey detection alone and prey detection with consumption had different
      informational effects. Total thread length did not differ between single and five
      prey-item detection spiders, but distance between two adjacent sticky spirals
      increased only in the former spiders, possibly because five times unsuccessful
      predations prevented spiders to reduce web stickiness. It suggests that the
      spider changed web morphology according to the number of prey detection.

PMID- 17534591
TI  - [Infratentorial tumors].
AB  - This article gives an overview concerning the typical infratentorial tumors of
      adults.

PMID- 17534592
TI  - The M flax rust resistance pre-mRNA is alternatively spliced and contains a
      complex upstream untranslated region.
AB  - Alternative splicing is an important step in controlling gene expression and has
      been shown to occur for a number of plant disease resistance (R) genes. The
      specific biological role of alternatively spliced transcripts from most R genes
      is unknown, yet in two cases it is clear that functional disease resistance
      cannot be activated without them. We report 12 splice isoforms of the M flax rust
      resistance gene, a TIR-NBS-LRR class of R gene. Collectively, these isoforms are
      predicted to encode at least nine different polypeptide products, only one of
      which is a full length peptide believed to confer functional M gene-specific
      disease resistance. An additional intron to that previously described was found
      in the 5' untranslated region. Splicing of this leader intron removes an upstream
      ORF (muORF) sequence. In some transcripts the leader intron is retained and in
      this case we predict negligible translation initiation of the full length M gene
      encoding ORF. The majority of the alternatively spliced isoforms of M would
      encode truncated TIR and TIR-NBS containing proteins. Although the role of
      alternative splicing and the existence and function of the products they encode
      is still unclear, the complexities of the splicing profile, and the 5' UTR of the
      M gene, are likely to serve in mechanisms to regulate R protein levels.

PMID- 17534594
TI  - Mapping QTLs with digenic epistasis under multiple environments and predicting
      heterosis based on QTL effects.
AB  - Mixed linear model approach was proposed for mapping QTLs with the digenic
      epistasis and QTL by environment (QE) interaction as well as additive and
      dominant effects. Monte Carlo simulations indicated that the proposed method
      could provide unbiased estimations for both positions and genetic main effects of
      QTLs, as well as unbiased predictions for QE interaction effects. A method was
      suggested for predicting heterosis based on individual QTL effects. The
      immortalized F(2) (IF(2)) population constructed by random mating among RI or DH
      lines is appropriate for mapping QTLs with epistasis and their QE interaction.
      Based on the models and methodology proposed, we developed a QTL mapping
      software, QTLMapper 2.0 on the basis of QTLmapper 1.0, which is suitable for
      analyzing populations of DH, RIL, F(2) and IF(2). Data of thousand grain weight
      of IF(2) population with 240 lines derived from elite hybrid rice Shanyou 63 were
      analyzed as a worked example.

PMID- 17534593
TI  - Complete chloroplast genome sequences of Hordeum vulgare, Sorghum bicolor and
      Agrostis stolonifera, and comparative analyses with other grass genomes.
AB  - Comparisons of complete chloroplast genome sequences of Hordeum vulgare, Sorghum
      bicolor and Agrostis stolonifera to six published grass chloroplast genomes
      reveal that gene content and order are similar but two microstructural changes
      have occurred. First, the expansion of the IR at the SSC/IRa boundary that
      duplicates a portion of the 5' end of ndhH is restricted to the three genera of
      the subfamily Pooideae (Agrostis, Hordeum and Triticum). Second, a 6 bp deletion
      in ndhK is shared by Agrostis, Hordeum, Oryza and Triticum, and this event
      supports the sister relationship between the subfamilies Erhartoideae and
      Pooideae. Repeat analysis identified 19-37 direct and inverted repeats 30 bp or
      longer with a sequence identity of at least 90%. Seventeen of the 26 shared
      repeats are found in all the grass chloroplast genomes examined and are located
      in the same genes or intergenic spacer (IGS) regions. Examination of simple
      sequence repeats (SSRs) identified 16-21 potential polymorphic SSRs. Five IGS
      regions have 100% sequence identity among Zea mays, Saccharum officinarum and
      Sorghum bicolor, whereas no spacer regions were identical among Oryza sativa,
      Triticum aestivum, H. vulgare and A. stolonifera despite their close phylogenetic
      relationship. Alignment of EST sequences and DNA coding sequences identified six
      C-U conversions in both Sorghum bicolor and H. vulgare but only one in A.
      stolonifera. Phylogenetic trees based on DNA sequences of 61 protein-coding genes
      of 38 taxa using both maximum parsimony and likelihood methods provide moderate
      support for a sister relationship between the subfamilies Erhartoideae and
      Pooideae.

PMID- 17534595
TI  - Negative inbreeding effects in tree fruit breeding: self-compatibility
      transmission in almond.
AB  - Inbreeding depression has been observed in most fruit trees, negatively affecting
      the offspring of related parents. This problem is steadily increasing due to the
      repeated utilization of parents in breeding programmes. In almond, self
      compatibility transmission from 'Tuono' to its offspring remains partially
      unexplained due to deviations from the expected genotype ratios. In order to test
      if these deviations could be due to inbreeding, the S-genotypes of the seedlings
      of four almond families, 'Tuono' (S(1)S(f )) x 'Ferragnes' (S(1)S(3)), 'Tuono'
      (S(1)S(f)) x 'Ferralise' (S(1)S(3)) and reciprocal crosses were studied. The S
      genotype determination of each seedling by separation of stylar S-RNases and by S
      allele-specific PCR amplification gave identical results. The ratio of S
      genotypes of the family 'Tuono' x 'Ferralise' was the one least adjusted to the
      expected 1:1 ratio, because the number of self-compatible seedlings (S(f)S(3))
      was less than a half the number of self-incompatible ones (S(1)S(3)). A mechanism
      acting against inbreeding would favour cross-breeding in the following generation
      to increase heterozygosity. This fact stresses the need to avoid crosses between
      related parents in fruit breeding programmes.

PMID- 17534596
TI  - Differential effects of fatness, fitness and physical activity energy expenditure
      on whole-body, liver and fat insulin sensitivity.
AB  - AIMS/HYPOTHESIS: The relative contributions of fitness (maximal oxygen uptake),
      physical activity energy expenditure (PAEE) and fatness to whole-body, liver and
      fat insulin sensitivity is uncertain. The aim of this study was to determine
      whether fitness and PAEE are associated with whole-body, liver and fat insulin
      sensitivity independently of body fat. MATERIALS AND METHODS: We recruited 25 men
      (mean [SD] age 53 [6] years). Whole-body (M value) and liver (percentage
      suppression of endogenous glucose output) insulin sensitivity were estimated
      using a hyperinsulinaemic-euglycaemic clamp. Insulin sensitivity in fat (insulin
      sensitivity index for NEFA) was estimated during an OGTT. Total and truncal fat
      were measured by dual-energy X-ray absorptiometry, fitness by treadmill, and PAEE
      (n = 21) by 3 day heart rate monitoring and Baecke questionnaire. RESULTS: In
      univariate analyses, fatness was strongly associated with insulin sensitivity
      (whole-body, liver and fat). Fitness was associated with whole-body (r = 0.53, p
      < 0.007) and liver (0.42, p = 0.04) insulin sensitivity, while PAEE was
      associated with liver insulin sensitivity (r = 0.55, p = 0.01). Regression models
      were established to describe associations between fatness, fitness and physical
      activity and measures of insulin sensitivity (whole-body, fat and liver) as
      outcomes. Only fatness was independently associated with whole-body insulin
      sensitivity (B coefficient -0.01, p = 0.001). Fitness was not associated with any
      outcome. Only PAEE was independently associated with liver insulin sensitivity (B
      coefficient 13.5, p = 0.02). CONCLUSIONS/INTERPRETATION: Fatness explains most of
      the variance in whole-body insulin sensitivity. In contrast, PAEE explains most
      of the variance in liver insulin sensitivity.

PMID- 17534598
TI  - Endoscopic assisted flexor hallucis tendon transfer in the management of chronic
      rupture of Achilles tendon.
AB  - Operative treatment is indicated in the management of chronic Achilles tendon
      rupture. Reconstruction of chronic Achilles tendon rupture can be classified into
      end-to-end repair, tendo Achilles advancement or flap reconstruction, local
      tendon transfer and implantation with autografts, allografts or synthetic
      materials. Following debridement of the tendon ends and with retraction of the
      proximal tendon fragment, a large gap will be present and direct tendon
      apposition with physiological tension is usually not possible. Flexor hallucis
      longus transfer is indicated if the tendon gap is more than 5 cm. We describe an
      endoscopic assisted flexor hallucis longus transfer in order to minimize the soft
      tissue dissection.

PMID- 17534597
TI  - [Postoperative physiotherapy in acute care--when, what and how much?].
AB  - This article documents the role of early musculoskeletal rehabilitation in acute
      care after orthopaedic surgery involving the hip, knee or spine. It discusses the
      open questions of the type, time and intensity of physiotherapeutic intervention.
      The role of standardized quality management to define clinical pathways is
      discussed.

PMID- 17534600
TI  - The arthroscopic management of femoroacetabular impingement.
AB  - Femoroacetabular impingement (FAI) has recently been implicated in causing a
      spectrum of injury ranging from anterior hip pain, labral tears, chondral damage,
      and eventually perhaps to idiopathic arthritis of the hip. Three distinct types
      have been described: cam, pincer and mixed, with the mixed one being the
      commonest. Surgical treatment of femoroacetabular impingement is focused towards
      providing an adequate clearance to alleviate femoral abutment against the
      acetabular rim. This is achieved by restoring a normal femoral head-neck offset
      and recessing the acetabular rim if necessary. The treatment of FAI has been
      achieved with reasonable success by open surgical dislocation as described by the
      Swiss group. However, the protracted post-operative recovery coupled with the
      trauma sustained during the open procedure, have led to the development of an
      arthroscopic approach to manage this problem. The purpose of this article is to
      provide the reader with an up-to-date knowledge of the clinical and diagnostic
      aspects of FAI, to describe our arthroscopic technique in detail with its
      pitfalls and possible complications and to discuss the results and future of FAI.

PMID- 17534599
TI  - Anatomic double bundle ACL reconstruction: a literature review.
AB  - With the abundance of anatomic double bundle ACL reconstruction techniques that
      currently exist and limited patient outcome data, one has to ask whether or not
      they should be used and if so, which one, and what is the learning curve for the
      average knee surgeon to become competent with the technique that they select? The
      purpose of this literature review is to summarize existing anatomic double bundle
      ACL reconstruction surgical and rehabilitation techniques and the clinical and
      biomechanical study evidence that currently exists. In choosing to perform
      anatomic double bundle ACL reconstruction we suggest that the knee surgeon should
      look for evidence of: (1) control of the pivot shift phenomenon, (2) improved
      transverse plane rotatory knee control during the performance of sports type
      movements, (3) a decreased likelihood of revision procedures either for ACL
      reconstruction or for treatment of associated primary or recurrent meniscal
      injuries, (4) improved patient self-reports of perceived function, satisfaction,
      and quality of life, and (5) radiographic evidence of a lower incidence and/or
      magnitude of osteoarthritic changes compared to conventional single bundle ACL
      reconstruction.

PMID- 17534601
TI  - Characterization of a broad range antibacterial substance from a new Bacillus
      species isolated from Amazon basin.
AB  - A Bacillus sp. strain producing a bacteriocin-like substance was characterized by
      biochemical profiling and 16S rDNA sequencing. The phylogenetic analysis
      indicated that this strain has low sequence similarity with most Bacillus spp.,
      suggesting a new species was isolated. The antimicrobial activity was detected
      starting at the exponential growth phase, and maximum activity was observed at
      stationary phase. The substance was inhibitory to a broad range of indicator
      strains, including pathogenic and food spoilage bacteria such as Listeria
      monocytogenes, B. cereus, Aeromonas hydrophila, Erwinia carotovora, Pasteurella
      haemolytica, Salmonella Gallinarum, among other. The antibacterial substance was
      stable over a wide pH range, but it was sensitive to pronase E and lipase. The
      antibacterial substance was bactericidal and bacteriolytic to L. monocytogenes
      and B. cereus at 160 AU ml(-1). The identification of a broad range bacteriocin
      like inhibitory substance active against L. monocytogenes addresses an important
      aspect of food protection against pathogens and spoilage microorganisms.

PMID- 17534602
TI  - Hydrolysis of acetylthiocholine iodide and reactivation of phoxim-inhibited
      acetylcholinesterase by pralidoxime chloride, obidoxime chloride and trimedoxime.
AB  - The hydrolysis of acetylthiocholine iodide (ATCh) by pralidoxime chloride (2-PAM
      Cl), trimedoxime (TMB(4)) and obidoxime chlpride (LUH(6)) was studied at pH 5.8
      8.0 and incubation temperature from 5 to 40 degrees C in vitro. Significant ATCh
      hydrolysis by 2-PAM Cl, TMB(4) and LUH(6) was found, with the exceptions of those
      at pH 7.0, 6.2 and 5.8 at 5 degrees C and those at pH 6.2 and 5.8 at 15 degrees
      C. The hydrolysis by TMB(4) and LUH(6) was significantly stronger than that by 2
      PAM Cl. The hydrolysis increased with increasing pH, incubation temperature and
      three oxime or ATCh concentration. Significant hydrolysis of ATCh by the three
      oximes could be found when the terminal concentration of oxime was higher than
      0.01 mM at pH 7.0 and 7.4 at 30 and 37 degrees C. However, no hydrolysis of
      natural substrate (acetylcholine iodide) by the three oximes was found when very
      high terminal concentrations of oximes were used. In addition, the three oximes
      displayed an extraordinary efficiency in the reactivation of phoxim-inhibited
      acetylcholinesterase (AChE) from fish (Carassius auratus) or rabbit (Oryctolagus
      cuniculus domestic) brain in vitro. Parallel to the level of ATCh hydrolysis by
      the oximes, TMB(4) and LUH(6) displayed significantly higher reactivation
      efficiency than 2-PAM Cl to phoxim-inhibited AChE. And, the extent of
      reactivation by 2-PAM Cl was also lower than the other two. Plausible antidotal
      actions of the oximes against organophosphate poisoning AChE and erroneously high
      estimation of AChE activity by the Ellman method were discussed.

PMID- 17534603
TI  - Activation of inwardly rectifying Kir2.x potassium channels by beta 3
      adrenoceptors is mediated via different signaling pathways with a predominant
      role of PKC for Kir2.1 and of PKA for Kir2.2.
AB  - beta(3)-adrenoceptors have recently been shown to induce a complex modulation of
      intracellular signaling pathways including cyclic guanine monophosphate, cyclic
      adenosine monophosphate, nitric oxide, and protein kinases A and C. They are
      expressed in a broad variety of tissues including the myocardium, vascular smooth
      muscle, and endothelium. In those tissues, resting membrane potential is
      controlled mainly by inwardly rectifying potassium channels of the Kir2 family
      namely, Kir2.1 in the vascular smooth muscle, Kir2.1-2.3 in the myocardium, and
      Kir2.1-2.2 in the endothelium. In the present study, we investigated the possible
      modulation of Kir2 channel function by beta(3)-adrenoceptors in an expression
      system. Human-cloned beta(3)-adrenoceptors and Kir2.1 (KCNJ2), Kir2.2 (KCNJ12),
      and Kir2.3 (KCNJ4) channels were coexpressed in Xenopus oocytes, and currents
      were measured with double-microelectrode voltage clamp. Activation of beta(3)
      adrenoceptors with isoproterenol resulted in markedly increased currents in
      Kir2.1 and in Kir2.2 potassium channels with EC50 values of 27 and 18 nM,
      respectively. In contrast, Kir2.3 currents were not modulated. Coapplication of
      specific inhibitors of protein kinase A (KT-5720) and calmodulin kinase II (KN
      93) had no effects on the observed regulation in Kir2.1. However, coapplication
      of protein kinase C (PKC) inhibitors staurosporine and chelerythrine suppressed
      the observed effect. In Kir2.2, coapplication of KT-5720 reduced the effect of
      beta(3)-adrenoceptor activation. No differences in current increase after
      application of isoproterenol were observed between mutant Kir2.2 potassium
      channels lacking all functional PKC phosphorylation sites and Kir2.2 wild-type
      channels. In heteromeric Kir2.x channels, all types of heteromers were activated.
      The effect was most pronounced in Kir2.1/Kir2.2 and in Kir2.2/Kir2.3 channels. In
      summary, homomeric and heteromeric Kir2.x channels are activated by beta(3)
      adrenoceptors via different protein kinase-dependent pathways: Kir2.1 subunits
      are modulated by PKC, whereas Kir2.2 is modulated by protein kinase A. In
      heteromeric composition, a marked activation of currents can be observed
      particularly with involvement of Kir2.2 subunits. This regulation may contribute
      to the hyperpolarizing effects of beta(3)-adrenoceptors in tissues that exhibit
      modulation by Kir2 channel function.

PMID- 17534604
TI  - Long-term administration of citalopram reduces basal and stress-induced
      extracellular noradrenaline levels in rat brain.
AB  - RATIONALE: Panic disorders are commonly treated with selective serotonin reuptake
      inhibitors (SSRIs). However, the effect of SSRIs on noradrenaline systems in the
      brain has not been fully elucidated at the present time. OBJECTIVES: The effects
      of long-term administration of citalopram, an SSRI, on basal as well as stress
      induced extracellular noradrenaline levels in the basolateral nucleus of the
      amygdala (BLA) and the locus coeruleus (LC) were determined. In addition, the
      responsiveness of noradrenaline transporters and alpha2-adrenoceptors were
      determined after long-term administration of citalopram. MATERIALS AND METHODS:
      Brain microdialysis was used to assess the extracellular levels of noradrenaline
      in conscious rats. Desipramine and clonidine were used to functionally evaluate
      the noradrenaline transporter and alpha2-adrenoreceptor, respectively. RESULTS:
      In rats treated daily for 14 days with citalopram (10 mg kg(-1) day(-1) s.c.),
      dialysate noradrenaline levels showed remarkable decreases in both the BLA and
      the LC to about 25 and 45% of controls, respectively. The stress-induced increase
      of noradrenaline was almost completely abolished in the BLA, but was relatively
      stable in the LC. The effect of local application of desipramine tended to be
      suppressed only in the LC. The effect of local application of clonidine was
      enhanced only in the BLA. CONCLUSION: The present results indicate that chronic
      administration of citalopram strongly decreases the extracellular levels of
      noradrenaline in the brain. The anti-panic effect of citalopram might be due to
      sensitization of the alpha2-adrenoceptors leading to suppression of the stress
      response through noradrenergic activity. This mechanism is specific for the BLA.

PMID- 17534605
TI  - Effects of sedative and non-sedative H1 antagonists on cognitive tasks:
      behavioral and near-infrared spectroscopy (NIRS) examinations.
AB  - RATIONALE: It is well known that the newer H1-receptor antagonists elicit better
      performance of working memory and selective attention relative to the first
      generation drugs in this class. However, the neural correlates of the poorer
      performance associated with first-generation H1-receptor antagonists remain
      unknown. OBJECTIVES: This study examined the effects of first- and second
      generation H1-receptor antagonists on neural correlates of cognitive tasks using
      near-infrared spectroscopy (NIRS), a novel method of brain imaging suitable for
      psychological experiments. MATERIALS AND METHODS: We measured the NIRS responses
      of 12 healthy volunteer subjects during the performance of working memory,
      selective attention, and visual perception tasks, 3 h after taking a first
      generation antagonist (ketotifen), second-generation antagonist (epinastine), or
      placebo. We also measured subjective sleepiness by visual analogue scale (VAS)
      test. RESULTS: Cortical activation at the lateral prefrontal region increased
      during the performance of working memory and selective attention tasks in
      subjects receiving epinastine and placebo but not in those who took ketotifen. No
      significant difference was observed at the occipital region in the visual
      perception task among the three drug groups. VAS score and the behavioral
      performance during working memory and visual perception tasks indicated sedative
      effects of ketotifen consistent with the findings of previous studies.
      CONCLUSIONS: Our results suggest that the neural response for working memory and
      selective attention task was impaired by the administration of ketotifen in
      comparison with that of epinastine and placebo. The sedative effect in the neural
      response was not observed after epinastine administration.

PMID- 17534606
TI  - Gold nanoparticle aggregation-based highly sensitive DNA detection using atomic
      force microscopy.
AB  - The potential ability of atomic force microscopy (AFM) as a quantitative
      bioanalysis tool is demonstrated by using gold nanoparticles as a size enhancer
      in a DNA hybridization reaction. Two sets of probe DNA were functionalized on
      gold nanoparticles and sandwich hybridization occurred between two probe DNAs and
      target DNA, resulting in aggregation of the nanoparticles. At high concentrations
      of target DNA in the range from 100 nM to 10 microM, the aggregation of gold
      nanoparticles was determined by monitoring the color change with UV-vis
      spectroscopy. The absorption spectra broadened after the exposure of DNA-gold
      nanoparticles to target DNA and a new absorption band at wavelengths >600 nm was
      observed. However, no differences were observed in the absorption spectra of the
      gold nanoparticles at low concentrations of target DNA (10 pM to 10 nM) due to
      insufficient aggregation. AFM was used as a biosensing tool over this range of
      target DNA concentrations in order to monitor the aggregation of gold
      nanoparticles and to quantify the concentration of target DNA. Based on the AFM
      images, we successfully evaluated particle number and size at low concentrations
      of target DNA. The calibration curve obtained when mean particle aggregate
      diameter was plotted against concentration of target DNA showed good linearity
      over the range 10 pM to 10 nM, the working range for quantitative target DNA
      analysis. This AFM-based DNA detection technique was three orders of magnitude
      more sensitive than a DNA detection method based on UV-vis spectroscopy.

PMID- 17534607
TI  - Optimisation of a selective method for the determination of organophosphorous
      triesters in outdoor particulate samples by pressurised liquid extraction and
      large-volume injection gas chromatography-positive chemical ionisation-tandem
      mass spectrometry.
AB  - A selective analytical method for the determination of nine organophosphate
      triesters and triphenylphosphine oxide (TPPO) in outdoor particulate matter is
      presented. It involves a fully automated pressurised liquid extraction (PLE)
      step, integrating an alumina clean-up process, and subsequent determination by
      large-volume injection gas chromatography-positive chemical ionisation-tandem
      mass spectrometry (LVI-GC-PCI-MS/MS). The extraction variables (solvent, amount
      of adsorbent, temperature, time and number of cycles) were optimised using a
      multicriteria strategy which implements a desirability function that maximises
      both extraction and clean-up efficiencies while searching for the best-compromise
      PLE conditions. The final method affords quantification limits of between 0.01
      and 0.3 microg g(-1) and recoveries of >80%, with the exceptions of the most
      polar analytes, TCEP and TPPO (~65%) for both urban dust and PM10 samples.
      Moreover, the method permitted the levels of these compounds in dust deposited
      outdoors (between LOD and 0.5 microg g(-1) for TEHP) and PM10 samples (between
      LOD and 2.4 microg m(-3) for TiBP) to be measured and reported for the first
      time.

PMID- 17534608
TI  - Anti-EPO and anti-NESP antibodies raised against synthetic peptides that
      reproduce the minimal amino acid sequence differences between EPO and NESP.
AB  - Erythropoietin (EPO) is a hormone that regulates red blood cell production.
      Recombinant human EPO (rHuEPO) and NESP (novel erythropoiesis stimulating
      protein) have been produced for therapeutic purposes and also to improve sports
      performance. The primary sequences of rHuEPO and NESP differ by just five amino
      acids. Due to the high homology, no antibodies that are able to discriminate
      between both molecules have been obtained until now. The aim of the present work
      was to design synthetic peptides corresponding to the sequence that differs
      between EPO and NESP (87-90aa), that can then be used as immunogens to develop
      specific rabbit polyclonal antibodies for selectively detecting EPO and NESP.
      Three peptides were synthesized: EPO (81-95), NESP (81-95), and NESP (86-104),
      and these were coupled to KLH and OVA for immunization and screening purposes,
      respectively. The sera obtained were tested by ELISA on synthetic peptide-OVA
      conjugates and purified by immunoaffinity chromatography against the
      corresponding synthetic peptide. The specific purified antibodies were
      characterized by ELISA, SDS-PAGE, and isoelectric focusing, followed by western
      blot. Antisera raised against EPO (81-95) recognized rHuEPO but not NESP. In
      contrast, anti-NESP (84-106) sera gave a specific anti-NESP response only after
      immunoaffinity purification on a NESP (86-91) column. An efficient strategy for
      generating specific antibodies against EPO and NESP can be achieved by selecting
      suitable synthetic peptides. The antibodies obtained are able to differentiate
      between rHuEPO and NESP, and may be particularly useful for screening purposes in
      both therapeutic and antidoping contexts.

PMID- 17534609
TI  - Red blood cells do not attenuate the SPCE fluorescence in surface assays.
AB  - We describe the positive effect of surface plasmon-coupled fluorescence emission
      (SPCE) on the detection of a signal from a surface immunoassay in highly
      absorbing or/and scattering samples. A model immunoassay using fluorescently
      labeled anti-rabbit antibodies that bind to rabbit immunoglobulin on a silver
      surface was performed, and the signal was detected in the presence of various
      highly absorbing and/or scattering solutions or suspensions, such as hemoglobin
      solution, plastic beads, and red blood cells. The results showed that a highly
      absorbing solution consisting of small molecules (dye, hemoglobin) attenuates the
      SPCE signal approximately 2-3-fold. In contrast, suspensions with the same
      absorption containing large particles (large beads, red blood cell suspension)
      attenuate the SPCE signal only slightly, approximately 5-10%. Also, a suspension
      of large undyed, highly scattering beads does not reduce the SPCE signal. The
      effects on the immunoassay signal of the sample background absorption and
      scattering, the size of the background particles, and the geometry of the
      experimental set-up are discussed. We believe that SPCE is a promising technique
      in the development of biosensors utilized for surface-based assays, as well as
      any assays performed directly in highly absorbing and/or scattering solutions
      without washing or separation procedures. Figure Red blood cells (unlike
      hemoglobin) do not attenuate the SPCE fluorescence in surface assays.

PMID- 17534610
TI  - Standard reference materials for foods and dietary supplements.
AB  - Well-characterized certified reference materials are needed by laboratories in
      the food testing, dietary supplement, and nutrition communities to facilitate
      compliance with labeling laws and improve the accuracy of information provided on
      product labels, so that consumers can make good choices. As a result of the
      enactment of the Nutrition Labeling and Education Act of 1990 and the Infant
      Formula Act of 1980, the National Institute of Standards and Technology (NIST)
      worked to develop a series of food-matrix standard reference materials (SRMs)
      characterized for nutrient concentrations. These include SRM 1544 Fatty Acids and
      Cholesterol in a Frozen Diet Composite, SRM 1546 Meat Homogenate, SRM 1548a
      Typical Diet, SRM 1566b Oyster Tissue, SRM 1846 Infant Formula, SRM 1946 Lake
      Superior Fish Tissue, SRM 1947 Lake Michigan Fish Tissue, SRM 2383 Baby Food
      Composite, SRM 2384 Baking Chocolate, SRM 2385 Slurried Spinach, and SRM 2387
      Peanut Butter. With the enactment of the Dietary Supplement Health and Education
      Act of 1994, NIST has been working to develop suites of dietary supplement SRMs
      characterized for active and marker compounds and for toxic elements and
      pesticides, where appropriate. An updated SRM 1588b Organics in Cod Liver Oil, a
      suite of ephedra-containing materials (SRMs 3240-3245), a carrot extract in oil
      (SRM 3276), and a suite of ginkgo-containing materials (SRMs 3246-3248) are
      available. Several other materials are currently in preparation. Dietary
      supplements are sometimes provided in forms that are food-like; for these, values
      may also be assigned for nutrients, for example SRM 3244 Ephedra-Containing
      Protein Powder. Both the food-matrix and dietary supplement reference materials
      are intended primarily for validation of analytical methods. They may also be
      used as "primary control materials" in assignment of values to in-house
      (secondary) control materials to confirm accuracy and to establish measurement
      traceability to NIST.

PMID- 17534611
TI  - Flow field-flow fractionation-inductively coupled optical emission spectrometric
      investigation of the size-based distribution of iron complexed to phytic and
      tannic acids in a food suspension: implications for iron availability.
AB  - Flow field-flow fractionation-inductively coupled plasma optical emission
      spectrometry (FlFFF-ICP-OES) was applied to achieve the size-based fractionation
      of iron in a food suspension in order to gain insights into iron availability.
      The binding of iron with phytic and tannic acids, employed as model inhibitors of
      iron availability in foods, was investigated at pH 2.0 (representing stomach
      fluid), pH 5.0 (the transition stage in the upper part of the duodenum), and pH
      7.0 (the small intestine). In the presence of phytic acid, iron was found as a
      free ion or it was associated with molecules smaller than 1 kDa at pH 2.0. Iron
      associated with molecules larger than 1 kDa when the pH of the mixture was raised
      to 5.0 and 7.0. In the presence of tannic acid, iron was again mostly associated
      with molecules smaller than 1 kDa at pH 2.0. However, at pH 5.0, iron and tannic
      acid associated in large molecules (approximately 25 kDa), while at pH 7.0, most
      of the iron was associated with macromolecules larger than 500 kDa. Iron size
      based distributions of kale extract and tea infusion containing phytic and tannic
      acids, respectively, were also examined at the three pH values, with and without
      enzymatic digestion. Without enzymatic digestion of the kale extract and the tea
      infusion at pH 2.0, most of the iron was released as free ions or associated with
      molecules smaller than 1 kDa. At other pH values, most of the iron in the kale
      extract and the tea infusion was found to bind with ~2 kDa and >500 kDa
      macromolecules, respectively. Upon enzymatic gastrointestinal digestion, the iron
      was not observed to bind to macromolecules >1 kDa but <500 kDa, due to the
      enzymatic breakdown of large molecules to smaller ones (<1 kDa).

PMID- 17534613
TI  - Study of the antifungal activity of Acinetobacter baumannii LCH001 in vitro and
      identification of its antifungal components.
AB  - An Acinetobacter strain, given the code name LCH001 and having the potential to
      be an endophytic antagonist, has been isolated from healthy stems of the plant
      Cinnamomum camphora (L.) Presl, guided by an in vitro screening technique. The
      bacterium inhibited the growth of several phytopathogenic fungi such as
      Cryphonectria parasitica, Glomerella glycines, Phytophthora capsici, Fusarium
      graminearum, Botrytis cinerea, and Rhizoctonia solani. Biochemical,
      physiological, and 16S rDNA sequence analysis proved that it is Acinetobacter
      baumannii. When the filtrate from the fermentation broth of strain LCH001 was
      tested in vitro and in vivo, it showed strong growth inhibition against several
      phytopathogens including P. capsici, F. graminearum, and R. solani, indicating
      that suppression of the growth of the fungi was due to the presence of antifungal
      compounds in the culture broth. Moreover, the antifungal activity of the culture
      filtrate was significantly correlated with the cell growth of strain LCH001. The
      active metabolites in the filtrate were relatively thermally stable, but were
      sensitive to acidic conditions. Three antifungal compounds were isolated from the
      culture broth by absorption onto macropore resin, ethanol extraction,
      chromatography on silica gel or LH-20 columns, and crystallization. The
      structures of the bioactive compounds were identified by spectroscopic methods as
      isomers of iturin A, namely, iturin A2, iturin A3, and iturin A6. The
      characterization of an unusual endophytic bacterial strain LCH001 and its
      bioactive components may provide an alternative resource for the biocontrol of
      plant diseases.

PMID- 17534612
TI  - Characterization of additional novel immune type receptors in channel catfish,
      Ictalurus punctatus.
AB  - Mining of channel catfish (Ictalurus punctatus) expressed sequence tag databases
      identified seven new novel immune type receptors (IpNITRs). These differed in
      sequence, but not structure, from previously described IpNITR1-11. IpNITR12a,
      12b, 13, and 14 encode proteins containing a single variable (V)-like
      immunoglobulin (Ig) domain. IpNITR12a and 13 encode a transmembrane (TM) region
      and cytoplasmic tail (CYT) containing immunoreceptor tyrosine inhibition motifs
      (ITIMs). IpNITR14 contains a TM and short CYT devoid of signaling motifs and is
      similar in structure to IpNITR7. IpNITR12b lacks a TM and may represent an
      IpNITR12a splice variant. In contrast, IpNITR15a, 15b, and 16 encode two Ig
      domains (V-like domain 1 and V/C2-like domain 2). IpNITR15a and 15b contain TM
      and CYT with ITIMs. IpNITR16 appears to be a secreted form. The first V-like
      domains of IpNITR12-16 (except a/b pairs) share 17-32% amino acid identity with
      each other and with V domains of IpNITR1-11. They therefore represent five
      additional IpNITR V families (defined as possessing 70% or more amino acid
      identity). The V/C2 domains of IpNITR15a, 15b and 16 have 94-98% amino acid
      identity, but share 37-50% amino acid identity with corresponding V/C2 domains
      found in IpNITR1-4. Phylogenetic analyses indicate IpNITR12-16 are more closely
      related to other teleost NITRs than to IpNITR1-11. Gene mapping indicates that
      IpNITRs are linked, and members of the ten known IpNITR families are
      interspersed. IpNITR12-16 are differentially expressed in various catfish immune
      type cells and preferentially up regulated in peripheral blood leukocytes by
      allogeneic stimulation.

PMID- 17534614
TI  - TNT biotransformation: when chemistry confronts mineralization.
AB  - Our understanding of the genetics and biochemistry of microbial 2,4,6
      trinitrotoluene (TNT) biotransformation has advanced significantly during the
      past 10 years, and biotreatment technologies have developed. In this review, we
      summarize this new knowledge. A number of enzyme classes involved in TNT
      biotransformation include the type I nitroreductases, the old yellow enzyme
      family, a respiration-associated nitroreductase, and possibly ring hydroxylating
      dioxygenases. Several strains harbor dual pathways: nitroreduction (reduction of
      the nitro group in TNT to a hydroxylamino and/or amino group) and denitration
      (reduction of the aromatic ring of TNT to Meisenheimer complexes with nitrite
      release). TNT can serve as a nitrogen source for some strains, and the postulated
      mechanism involves ammonia release from hydroxylamino intermediates. Field
      biotreatment technologies indicate that both stimulation of microbial
      nitroreduction and phytoremediation result in significant and permanent
      immobilization of TNT via its metabolites. While the possibility for TNT
      mineralization was rekindled with the discovery of TNT denitration and
      oxygenolytic and respiration-associated pathways, further characterization of
      responsible enzymes and their reaction mechanisms are required.

PMID- 17534615
TI  - Bone and marrow imaging: do we know what we see and do we see what we want to
      know?

PMID- 17534616
TI  - Isometric measurement of wrist-extensor power following surgical treatment of
      displaced lateral condylar fracture of the humerus in children.
AB  - Muscle disability is a common sequel after fracture management. Previous research
      has shown divergent results concerning muscle-power recovery after bone healing.
      This study has investigated the muscle function of wrist extensors after lateral
      condylar fracture in children, as evaluated by a hand-held dynamometer and
      compared with sex- and age-matched children. From 1999 to 2004, 20 patients (13
      boys and seven girls; mean age: 9 years and 4 months) with displaced lateral
      condylar fracture of the humerus were treated by open reduction and internal
      fixation with Kirschner wires (K-wire). The duration of K-wire fixation was 35
      days and the mean follow-up time was 50 months. A total of 180 healthy age-, sex-
      and weight-matched children were used as control groups. A paired Student's test
      was applied for the analysis of statistical significance. The range of motion of
      the elbow and radiographic findings were not significantly different between the
      injured limb and normal control groups. The maximum isometric power of wrist
      extensor muscles after surgical treatment of lateral condylar fracture of the
      humerus in final follow-up was not statistically different from that in the
      normal control children. Muscle power therefore recovers to its normal status
      after the healing of lateral condylar fracture of the humerus in children.

PMID- 17534618
TI  - Comment on Sadiq et al.: Management of grade III supracondylar fracture of the
      humerus by straight-arm lateral traction.

PMID- 17534619
TI  - Outcome evaluation measures for wrist and hand: which one to choose?
AB  - The aim of this study was to critically analyse the various outcome measures
      available for assessing wrist and hand function. To this end, an extensive
      literature search was performed on Medline, PubMed and the Science Citation
      Index, focusing on terms associated with the method of development of the outcome
      measures item generation, item reduction, validity, reliability, internal
      consistency and their strengths and weaknesses. The most commonly used outcome
      measures described in literature were the DASH score (disability of shoulder, arm
      and hand questionnaire), the PRWE score (patient-rated wrist evaluation
      questionnaire), the Brigham and Women's carpal tunnel questionnaire and the
      Gartland and Werley score. Our study provides very useful evidence to suggest
      that the PRWE score is the most responsive instrument for evaluating the outcome
      in patients with distal radius fractures, while the DASH score is the best
      instrument for evaluating patients with disorders involving multiple joints of
      the upper limb. The Brigham and Women's score is a disease-specific outcome
      instrument for carpal tunnel syndrome; it has been validated and demonstrated to
      show good responsiveness and reliability in evaluating outcome in patients with
      carpal tunnel release. The Gartland and Werley score, although the most commonly
      described instrument in the literature for evaluating outcome after wrist
      surgery, has not been validated so to date.

PMID- 17534620
TI  - Self-optimization, community stability, and fluctuations in two individual-based
      models of biological coevolution.
AB  - We compare and contrast the long-time dynamical properties of two individual
      based models of biological coevolution. Selection occurs via multispecies,
      stochastic population dynamics with reproduction probabilities that depend
      nonlinearly on the population densities of all species resident in the community.
      New species are introduced through mutation. Both models are amenable to exact
      linear stability analysis, and we compare the analytic results with large-scale
      kinetic Monte Carlo simulations, obtaining the population size as a function of
      an average interspecies interaction strength. Over time, the models self-optimize
      through mutation and selection to approximately maximize a community potential
      function, subject only to constraints internal to the particular model. If the
      interspecies interactions are randomly distributed on an interval including
      positive values, the system evolves toward self-sustaining, mutualistic
      communities. In contrast, for the predator-prey case the matrix of interactions
      is antisymmetric, and a nonzero population size must be sustained by an external
      resource. Time series of the diversity and population size for both models show
      approximate 1/f noise and power-law distributions for the lifetimes of
      communities and species. For the mutualistic model, these two lifetime
      distributions have the same exponent, while their exponents are different for the
      predator-prey model. The difference is probably due to greater resilience toward
      mass extinctions in the food-web like communities produced by the predator-prey
      model.

PMID- 17534621
TI  - Epidemiological multicenter study on osteoporosis: the EDMUSTO study.

PMID- 17534622
TI  - Chitotriosidase as a marker of disease activity in sarcoidosis.
AB  - Sarcoidosis is a chronic granulomatous inflammation. The clinical spectrum in
      childhood is heterogeneous. Angiotensin converting enzyme (ACE) activity is used
      as a marker for disease activity. Human chitotriosidase is produced in
      macrophages. In this study serum chitotriosidase levels were significantly higher
      in active sarcoidosis, than in inactive disease or healthy controls. Serum
      chitotriosidase concentrations may be a useful marker for monitoring disease
      activity in sarcoidosis.

PMID- 17534623
TI  - Superoxide anion regulates plant growth and tuber development of potato.
AB  - A higher concentration of H2O2 was detected in the sense transgenic potato plant
      (SS4) with the lily chCu,ZnSOD sequence, whereas higher levels of O2(-) was
      detected in the antisense transgenic plant (SA1) than the WT plant. The
      elongation growth in SA1 was significantly inhibited by treatment with
      diphenyleneiodonium, an inhibitor of O2(-) generation, and promoted in the SS4 on
      treatment with herbicide methyl viologen, a generator of apoplastic O2(-) .
      Higher concentrations of GAs were detected during plant growth and the early
      stage of tuberization in SA1. Complete recovery of the above elongation growth
      and microtuberization pattern in transgenic plants following treatment of GA(3)
      or an inhibitor of gibberellin synthesis, paclobutrazol, indicate that these
      changes were mainly caused by active GA levels. In conclusion, a specific ROS
      (O2(-) ) acts as a signal transducer via GA biosynthetic pathways for the
      regulation of plant growth and tuber development of potato.

PMID- 17534624
TI  - Analysis of the limitations of hepatitis B surface antigen expression in soybean
      cell suspension cultures.
AB  - Soybean cell suspension cultures were transformed using Agrobacterium tumefaciens
      harboring pHBS/pHER constructs to express hepatitis B surface antigen (HBsAg).
      The transformed colonies were selected and analyzed for the expression of HBsAg
      by PCR, reverse transcription (RT) PCR, Western blot and ELISA analysis. The
      maximum expression of 700 ng/g F.W. was noted in pHER transformed cells. The
      highest expressing colonies were used to initiate the cell suspension cultures
      and the expression of HBsAg was estimated periodically. The expression levels
      were reduced drastically in cell suspension cultures compared to the colonies
      maintained on semi-solid medium. Various parameters were studied to maximize the
      cell growth and to retain the expression levels. The supplementation of culture
      medium with a protease inhibitor, leupeptin hemisulfate could restore up to 50%
      of HBsAg expression in cell suspension cultures. This is the first report to
      investigate the possible cause and solution to the loss of recombinant protein
      expression levels in plant cell suspension cultures.

PMID- 17534625
TI  - Technical aspects of lasers in urology.
AB  - During the course of history a variety of laser principles have been introduced
      in surgery. Some erroneous developments probably could have been kept out of the
      market place if not for the magic which accompanies the acronym LASER and with
      more understanding for the underlying principles governing the process when light
      meets tissue. The interaction of light with tissue is exemplified on the basis of
      natural body chromophores when compared with available lasers at different
      wavelengths and operational modes. Furthermore the meaning of fibre flexibility
      and durability is elucidated.

PMID- 17534627
TI  - [Fused eyelids in a neonate with ventricular septal defect. Diagnosis: AFA].

PMID- 17534626
TI  - The impact of obesity on prostate cancer.
AB  - Increasing prevalence of obesity in many parts of the world emphasizes the
      importance of learning more about the relationship between obesity and prostate
      cancer (PC). The present paper reviews the impact of obesity on PC using
      knowledge obtained from the available literature. Search of published literature
      in PUBMED database. Adipose tissue constitutes an active endocrine and metabolic
      organ which may be relevant in the development and progression of PC by different
      potential mechanisms. Furthermore, obesity could have an impact on the outcome of
      different treatment modalities for PC, both functionally as anatomically. Obesity
      is a growing problem, however, the exact role in the development and progression
      of PC has not been elucidated. Regarding the optimal treatment of PC in obese
      patients, comparative prospective studies are needed.

PMID- 17534628
TI  - The generation of DPOAEs in the locust ear is contingent upon the sensory
      neurons.
AB  - Tympanal organs of insects emit distortion-product otoacoustic emissions (DPOAEs)
      that are indicative of nonlinear ear mechanics. Our study sought (1) to define
      constraints of DPOAE generation in the ear of Locusta migratoria, and (2) to
      identify the sensory structures involved. We selectively destroyed the connection
      between the (peripheral) sensory ganglion and the tympanal attachment points of
      the "d-cell" dendrites; d-cells are most sensitive to sound frequencies above 12
      kHz. This led to a decrease of DPOAEs that were evoked by f (2) frequencies above
      15 kHz (decrease of 15-40 dB; mean 28 dB; n = 12 organs). DPOAEs elicited by
      lower frequencies remained unchanged. Such frequency-specific changes following
      the exclusion of one scolopidial sub-population suggest that these auditory
      scolopidia are in fact the source of DPOAEs in insects. Electrical stimulation of
      the auditory nerve (with short current pulses of 4-10 microA or DC-currents of
      0.5 microA) reversibly reduced DPOAEs by as much as 30 dB. We assume that
      retrograde electrical stimulation primarily affected the neuronal part of the
      scolopidia. Severing the auditory nerve from the central nervous system (CNS) did
      not alter the DPOAE amplitudes nor the effects of electrical stimulation.

PMID- 17534629
TI  - Associative learning and discrimination of motion cues in the harnessed honeybee
      Apis mellifera L.
AB  - We previously studied a conditioning paradigm to associate the proboscis
      extension reflex (PER) with monochromatic light (conditioned stimulus; CS) in
      harnessed honeybees. Here, we established a novel conditioning paradigm to
      associate the PER with a motion cue generated using graphics interchange format
      (GIF) animations with a speed of 12 mm/s speed and a frame rate of 25 Hz as the
      CS, which were projected onto a screen consisting of a translucent circular cone
      that largely covered the visual field of the harnessed bee using two liquid
      crystal projectors. The acquisition rate reached a plateau at approximately 40%
      after seven trials, indicating that the bees were successfully conditioned with
      the motion cue. We demonstrated four properties of the conditioning paradigm.
      First, the acquisition rate was enhanced by antennae deprivation, suggesting that
      sensory input from the antennae interferes with the visual associative learning.
      Second, bees conditioned with a backward-direction motion cue did not respond to
      the forward-direction, suggesting that bees can discriminate the two directions
      in this paradigm. Third, the bees can retain memory for motion cue direction for
      48 h. Finally, the acquisition rate did not differ significantly between foragers
      and nurse bees.

PMID- 17534630
TI  - Chiari I malformation and idiopathic growth hormone deficiency in siblings:
      report of three cases.
AB  - INTRODUCTION: The authors report a case of three brothers. CASE DESCRIPTIONS: Two
      of these siblings presented with congenital growth hormone deficiency (GHD) and
      Chiari I malformation (CIM). The third younger brother has been found not to have
      GHD or the CIM. DISCUSSION: Sparse cases of these two clinical occurrences have
      been reported. Further, the posterior cranial fossa (PF) has been determined to
      be altered in patients with CIM and GHD. CONCLUSION: Our current case reports
      strengthen the association between these two pathological entities and, to our
      knowledge, is the first description of both defects in siblings.

PMID- 17534631
TI  - Idiopathic fibrosing pancreatitis and spontaneous resolution of pancreatic masses
      in children.
AB  - A symptomatic pancreatic mass poses both a diagnostic and therapeutic conundrum.
      First, benign conditions may mimic malignancy and second, the management of
      benign lesions has not been well defined. We reviewed four such cases and discuss
      the management of juvenile idiopathic fibrosing pancreatitis in the light of
      these. In four children with symptomatic pancreatic masses/enlargement (three
      with jaundice) all resolved spontaneously without definitive intervention.
      Histopathology, obtained in two cases, revealed a fibrotic chronic inflammatory
      reaction. Pancreatic masses in children may not be malignant. Resolution of
      symptoms including obstructive jaundice and a mass secondary to juvenile
      idiopathic fibrosing pancreatitis may occur spontaneously, avoiding the need for
      resection or definitive drainage procedures.

PMID- 17534632
TI  - Acute suppurative thyroiditis in children secondary to pyriform sinus fistula.
AB  - Acute suppurative thyroiditis (AST), a potential complication of pyriform sinus
      fistula (PSF), is a rare clinical condition as the thyroid gland is remarkably
      resistant to infections. Lack of awareness of the entity contributes to the
      rarity and frustrating recurrences. We performed a retrospective review of all
      cases of AST due to PSF treated at our institution over a 10-year period. The
      clinical data, investigations, operative findings and procedures, microbial
      culture reports and follow-up were recorded and analyzed. Between January 1997
      and September 2006, 12 cases (8 males and 4 females) of AST due to PSF were
      treated. Nine patients (75%) underwent successful complete excision, seven of
      whom had initial incision and drainage procedures. In three patients (25%) with
      recurrence, one underwent complete excision at a later procedure, one patient had
      multiple recurrences with six incision and drainage procedures and two failed
      attempts of excision of PSF before final successful complete excision. The third
      patient is awaiting re-excision of the PSF tract. All patients, except the one
      awaiting re-excision, are well with no further recurrences during the follow-up
      period that ranged from 18 to 96 months (median, 46.5 months). AST due to PSF is
      a challenging entity in terms of diagnosis and management as recurrences are
      common despite meticulous dissection. High index of suspicion and radiological
      investigations such as barium studies and computed tomography scan aid in the
      delineation and excision of the fistulous tract.

PMID- 17534633
TI  - Surgical predictors of recurrence of Crohn's disease after ileocolonic resection.
AB  - BACKGROUND/AIMS: Anastomotic recurrence after bowel resection is a major problem
      in Crohn's disease (CD) surgery. The aims of this retrospective study are to
      assess the role of anastomotic configuration, the type of suture and the type of
      surgical approach (laparoscopy-assisted vs laparotomy) in CD recurrence.
      Secondary end points were to identify any possible predictor that would help the
      selection of patients for medical prophylaxis. MATERIALS AND METHODS: In this
      retrospective study, we enrolled 141 consecutive patients who had undergone
      ileocolonic resection for CD. Univariate actuarial analysis was performed
      according to demographic, clinical and surgical predictors. Variables that
      resulted to be significant at the univariate analysis were included in two
      multivariate Cox proportional hazards models that analyzed symptomatic and
      surgical recurrence, respectively. RESULTS: In the long-term, handsewn side-to
      side anastomosis reported a significantly lower surgical recurrence rate than
      stapled end-to-side (p < 0.05). At multivariate analysis, anastomosis type,
      surgical and intestinal complications (p < 0.01) and age at CD onset (p < 0.05)
      resulted to be significant predictors for re-operation for CD recurrence.
      Multivariate analysis showed that surgical complication was also a significant
      predictor of symptomatic recurrence. CONCLUSIONS: Side-to-side anastomosis
      configuration seems to delay re-operation and can be assumed as the standard
      configuration in ileocolonic anastomosis in CD. Post-operative complications and
      young age at disease onset might be a signal of aggressive CD that may warrant
      prophylactic pharmacological therapy.

PMID- 17534634
TI  - 1% hydrocortisone ointment is an effective treatment of pruritus ani: a pilot
      randomized controlled crossover trial.
AB  - BACKGROUND: Pruritus ani (PA) is a common condition which is difficult to treat
      in the absence of obvious predisposing factors. There is paucity of evidence
      based guidelines on the treatment of this condition. We examined whether 1%
      hydrocortisone ointment is an effective treatment for PA. MATERIALS AND METHODS:
      A pilot randomized, double-blind, placebo-controlled, crossover trial was carried
      out. Eleven patients consented to take part in the trial and ten completed the
      study. After a 2-week run-in period, patients with primary PA were randomly
      allocated to receive 1% hydrocortisone ointment or placebo for 2 weeks followed
      by the opposite treatment for a further 2-week period. There was a washout period
      of 2 weeks between treatments. The primary outcome measure was reduction in itch
      using a visual analogue score (VAS). The secondary outcome measures were
      improvement in quality of life measured using a validated questionnaire
      (Dermatology Life Quality Index, DLQI) and improvement in clinical appearance of
      the perianal skin using the Eczema Area and Severity Index (EASI) score. RESULTS:
      Treatment with 1% hydrocortisone ointment resulted in a 68% reduction in VAS
      compared with placebo (P=0.019), a 75% reduction in DLQI score (P=0.067), and 81%
      reduction in EASI score (P=0.01). CONCLUSION: A short course of mild steroid
      ointment is an effective treatment for PA.

PMID- 17534635
TI  - Awful considerations with LCP instrumentation: a new pitfall.
AB  - INTRODUCTION: Although the locking compression plate (LCP) system offers a number
      of advantages in fracture management, its successful use requires careful
      preoperative planning, consideration of soft tissue dissection principles, and
      good surgical technique. Failure to address these issues can lead to potential
      pitfalls. Therefore, there are many reports about potential pitfalls that can
      arise with inappropriate LCP instrumentation technique. Moreover, these studies
      may mislead the orthopaedic colleagues that the only important tip in LCP using
      is its mechanical considerations. But, there is no study about the potential soft
      tissue pitfalls that may occur. There is an attempt in this study to achieve this
      objective. METHODS: A prospective analysis was carried out on all patients who
      were hospitalized for metaphyseal fracture of tibia and LCP fixation was done for
      them in our trauma center over a 6-month period in 2003. Inclusion criteria
      included all patients with fracture of tibial metaphysis who were to undergo
      locking compression plating using long conventional incision (without percutaneus
      insertion). Therefore, 34 patients included. RESULTS: Many patients (23.5%)
      developed severe soft tissue damage with exposed plate, and all of them need flap
      coverage. CONCLUSION: Locking compression plates have a higher profile in
      comparison to DCP, requiring careful attention to soft tissue. Therefore,
      inadvisable locking compression plating with conventional incision method and
      retaining anatomical reduction of the fracture can lead to a higher soft tissue
      complication in comparison to dynamic compression plating.

PMID- 17534636
TI  - Circulating pemphigus autoantibodies in healthy relatives of pemphigus patients:
      coincidental phenomenon with a risk of disease development?
AB  - Pemphigus is a severe autoimmune disease characterized by circulating and bound
      in vivo pemphigus autoantibodies. It was revealed that the autoantibodies occur
      in healthy first-degree relatives of pemphigus patients; however, their
      significance is not fully elucidated. Thus, the aim of the study was to assess
      the frequency of circulating IgG pemphigus autoantibodies in the healthy
      relatives of pemphigus patients and of their ability to bind in vivo in the
      epidermis. We also analyzed IgG subclasses distribution, both in the serum
      positive relatives and in the patients. Our study included 67 healthy relatives,
      50 healthy normal controls and 33 patients (25 at an active stage of the disease,
      8 in clinical remission). To detect circulating pemphigus antibodies we applied
      indirect immunofluorescence and anti-desmoglein ELISA. Monoclonal anti-human
      IgG1, IgG2, IgG3, IgG4 antibodies were used to assess subclass distribution. The
      frequency of circulating pemphigus autoantibodies in the relatives, detected by
      IIF (30/67) was statistically higher (P < 0.001) than in the control group
      (0/50). ELISA revealed anti-desmoglein 1 and/or 3 antibodies in 13 out of 67
      relatives. Direct immunofluorescence performed in 25 out of 32 seropositive
      relatives did not show intercellular bound in vivo IgG and/or C3 in the epidermis
      in any cases. Circulating IgG2 subclass was observed in 60% of the examined
      relatives and IgG4 was detected in 23.3% of them. In the patients at an active
      stage of pemphigus IgG4 and IgG1 were the dominant subclasses (96 and 76%
      relatively) while in clinical remission antibodies predominantly belonged to the
      IgG2 (75%) and IgG4 (37.5%) subclass. The obtained results confirmed polyclonal
      production of pemphigus autoantibodies and their different distributions
      dependent on the disease activity. Statistical analysis showed that the frequency
      of IgG1 and IgG4 subclasses was significantly higher in the patients at an active
      stage of the disease when compared to the patients in clinical remission (P <
      0.001) or with seropositive healthy relatives (P < 0.001). The relevance of the
      presence of IgG4 autoantibodies in the healthy relatives' sera requires further
      studies that focus on their potential pathogenicity.

PMID- 17534637
TI  - Primary and non-primary parotid malignancies: comparison of treatment modalities
      and outcomes.
AB  - Our aim was to report our experience in the management of malignant primary and
      non-primary parotid neoplasms and to compare the clinical presentations, the
      treatment modalities and the outcomes in these two groups. We performed a
      retrospective review of the clinical and surgical data contained in patient
      files. Between January 1995 and December 2004, 60 patients with malignant parotid
      tumors were admitted to our department. Two groups were isolated: a group of 42
      patients with primary parotid malignancies (group 1) and a group of 18 patients
      with non-primary parotid malignancies (intra-parotid metastasis and parotid
      lymphoma), (group 2). We compared the preoperative data, the surgical procedures
      performed total parotidectomy (TP) versus superficial parotidectomy (SP), the
      need for sacrificing the facial nerve and postoperative facial nerve function in
      the two groups. Actuarial survival rates were calculated using the Kaplan-Meier
      method in combination with the Log Rank test for comparison of the results in the
      two groups. Preoperative clinical facial nerve impairment was significantly more
      frequent in group 1 (33%) as compared to group 2 (6%) (P = 0.023). A SP was
      performed in 15 patients in group 2 while a TP was performed in 37 patients in
      group 1. The facial nerve was completely or partially sacrificed in 17 cases in
      group 1 and in only one case in group 2 (P = 0.03). One month after surgery, 18
      patients in group 1 had persistent facial nerve dysfunction compared to only one
      patient in group 2 (P = 0.004). In group 1, the overall 1, 3 and 5-year survival
      rates were, respectively, 94, 76 and 69%. In group 2, the respective survival
      rates were 84, 62 and 40% (P = 0.4). This study outlines the differences in
      clinical presentation, surgical management and outcomes in the two main groups of
      malignant parotid tumors. The prognosis of facial nerve function was better in
      non-primary parotid malignancies. SP was the standard surgical option in group 2
      patients while a TP was performed in the majority of the patients in group 1.
      Except when melanoma or lymphoma were present (which require specific treatment),
      adjuvant radiotherapy had the same indications in both groups when the tumors
      were high-grade, AJCC stages III and IV or when they had positive margins or
      lymph node and facial nerve involvement.

PMID- 17534638
TI  - Pathogenesis of sinus cholesteatoma.
AB  - The aim of the present study was to provide evidence for the establishment of
      sinus cholesteatoma, defined as postero-superior pars tensa retraction extending
      into the posterior tympanum and tympanic sinuses. BACKGROUND: There is clinical
      evidence for formation of a retraction, but there is a lack of explanation for
      the transition from a retraction pocket to an active and expanding sinus
      cholesteatoma. Epidemiological studies on incidence of postero-superior
      retractions of pars tensa and follow-up studies on patients with similar pars
      tensa retractions were performed. Additionally, expression of proliferation
      marker and analysis of basement membrane were studied in samples of sinus
      cholesteatoma. The prevalence of pars tensa pathology was between 9.2 and 24% of
      investigated ears. In children with manifest secretory otitis there were some
      sinus cholesteatomas and 5-6% severe retractions, some of those became pre
      cholesteatomas, requiring treatment and controls. Immunohistochemistry of sinus
      cholesteatomas showed that proliferating keratinocytes were very often found
      within epithelial cones growing towards the underlying stroma. These growth cones
      exhibit focal discontinuities of the basement membrane especially in areas of
      intense subepithelial inflammation. As a possible explanation based on clinical
      and immunohistochemical findings, we propose a four-step concept for pathogenesis
      of sinus cholesteatoma combining the retraction and proliferation theory: (1) The
      retraction pocket stage. (2) The proliferation stage of the retraction pocket,
      subdivided in (a) Cone formation, (b) Cone fusion. (3) Expansion stage of attic
      cholesteatoma. (4) Bone resorption.

PMID- 17534639
TI  - Invasive aspergillosis of the paranasal sinuses and the skull base.
AB  - Invasive aspergillosis (IA) originating from the paranasal sinuses can cause an
      intracranial growth mainly along the skull base and larger vessels. This study
      reports our experience in the diagnosis and treatment of a series of patients
      with IA. A retrospective chart review of four patients with chronic invasive
      intracranial aspergillosis was performed. Clinical signs, physical examinations,
      radiographs, histological samples, and outcome were demonstrated. The patients
      demonstrated different symptoms like exophthalmus, ophthalmoplegia, loss of
      vision, and hypaesthesia of the ophthalmic and maxillary nerve. Computed
      tomography and MRI revealed extensive sino-orbital and skull base lesions. The
      patients were treated with aggressive endonasal debridement, intravenous
      antifungal agents and daily irrigations with antimycotic suspensions.
      Furthermore, we applied hyperbaric oxygenation. Two patients died from
      complications due to subarachnoidal hemorrhage and accompanied complications
      respectively. Despite the high mortality rate patients with an invasive
      aspergillosis can be effectively treated in some cases by an early and rigorous
      treatment schedule using all surgical and conservative therapeutic options.

PMID- 17534640
TI  - Phonosurgery after endoscopic cordectomies. I. Primary intracordal autologous fat
      injection after transmuscular resection: preliminary results.
AB  - Treatment of glottic cancer by CO(2) laser endoscopic cordectomies can be
      associated with poor vocal outcome when the excision is extended beyond the
      superficial part of the thyro-arytenoid muscle. Different phonosugical techniques
      have been described in order to improve postoperative vocal outcome in patients
      undergoing this type of surgery. We herein present a new device for augmentation
      of residual vocal cord by video-endoscopic assisted primary intracordal
      autologous fat injection (PIAFI) performed at the end of transmuscular
      cordectomy. Twenty-four patients underwent transmuscular cordectomy and PIAFI for
      Tis and T1a glottic cancer. Eight cc of abdominal fat were obtained during the
      endoscopic procedure and processed. Infusion of intact parcels of fat tissue was
      performed to maximally reduce its resorption. PIAFI was performed in the residual
      vocal cord obtaining its immediate medialization, using a new device that
      permitted modulated (0.5 cc per click) injection. Fourteen patients were
      submitted to postoperative voice evaluation including subjective, perceptual, and
      objective assessment. The results were compared with those of 24 patients treated
      by transmuscular (Type III) cordectomy without subsequent PIAFI. No complications
      were observed as a result of PIAFI and the procedure did not significantly
      prolong overall surgical time. All patients were discharged the day after
      surgery. Comparison of vocal outcomes according to the Mann-Whitney and Wilcoxon
      tests showed a positive trend for patients submitted to PIAFI in terms of
      subjective and objective analysis. By contrast, a statistically significant
      improvement was reached in terms of perceptual analysis when comparing patients
      treated by Type III cordectomy alone with those submitted to this kind of
      procedure followed by PIAFI.

PMID- 17534641
TI  - Phonosurgery after endoscopic cordectomies. II. Delayed medialization techniques
      for major glottic incompetence after total and extended resections.
AB  - Major glottic incompetence is often encountered after total (Type IV) and
      extended (Type V) cordectomies and is responsible for poor vocal outcome. Even
      though the vast majority of patients do not complain of significant limitations
      in daily life, a selected number of them eventually require some sort of
      phonosurgical treatment in order to improve voice quality. Different techniques
      have been described in the literature to ameliorate long-term vocal outcome. The
      aim of the present report was to retrospectively describe our experience in this
      challenging clinical scenario. Between April 1999 and March 2005, 24 patients
      previously treated by Type IV-V endoscopic cordectomies for T1 and T2 glottic
      cancer presented unsatisfactory vocal outcome in spite of intensive speech
      therapy and therefore underwent some form of phonosurgical treatment at our
      Department after at least 12 months without evidence of local-regional
      recurrence. Patients were treated by medialization thyroplasty with a Montgomery
      System Implant (two cases), Gore-Tex strips (16 cases), medialization thyroplasty
      with Gore-Tex associated with anterior commissure laryngoplasty (three cases),
      and augmentation with Vox Implant injection (three cases). Nineteen patients had
      comprehensive evaluation by videolaryngoscopic examination and subjective,
      perceptual, and objective voice analysis both in the pre-phonosurgical treatment
      period and after at least 12 months. Comparison of pre- and postoperative
      videolaryngoscopic findings revealed improved glottic closure in 74% of patients.
      Comparison between the pre- and postoperative subjective, perceptual, and
      objective voice analysis by the Wilcoxon matched-pair test showed a statistically
      significant improvement from a Voice Handicap Index mean value of 46
      (preoperative) to 21 (postoperative); an improvement for each parameter of the
      GRBAS scale with statistically significant differences for G, B, A, and S, while
      R showed only an improving trend; and statistically significant improvement in
      the mean values of Jitter, Shimmer, Noise to Harmonic Ratio, and Maximum
      Phonation Time. In conclusion, the different delayed phonosurgical procedures
      herein used demonstrate the possibility to improve vocal outcomes after total and
      extended cordectomies in selected and highly motivated patients that have not
      achieved satisfactory performance after prolonged and intensive speech therapy.

PMID- 17534642
TI  - First successful assay of Y-SNP typing by SNaPshot minisequencing on ancient DNA.
AB  - In the present study, a set of 13 Y-chromosomal single nucleotide polymorphisms
      (Y-SNPs) selected for the identification of the most frequent Asian Y-haplogroups
      was included in an allele-specific primer extension assay. Single nucleotide
      polymorphism (SNP) genotyping was accomplished by co-amplification of these 13
      DNA fragments within 2 multiplex PCRs followed by detection with 1 minisequencing
      reaction using the SNaPshottrade mark Multiplex kit and analysis of extension
      products by capillary electrophoresis. First developed on modern samples, the
      assay was optimized for the analysis of 11 ancient DNA (aDNA) samples from the
      Krasnoyarsk region (southern Siberia) that were dated from 5,500-1,800 years
      before present (YBP). SNP typing was successful for most of them, which were all
      assigned to Y-haplogroup R1a1 except one. These results show that SNPs are well
      suited for the analysis of aged and degraded DNA samples. Moreover, we found that
      the SNaPshot minisequencing methodology is a convenient, robust, and efficient
      method for SNP typing. To our knowledge, this study reports the first successful
      investigation of Y-SNPs on aDNA samples. The potential use of Y-SNPs in both
      evolutionary and forensic fields is also discussed.

PMID- 17534643
TI  - Evaluation of the limits to accurate sweat loss prediction during prolonged
      exercise.
AB  - Sweat prediction equations are often used outside their boundaries to estimate
      fluid requirements and generate guidance. The limitations associated with these
      generalized predictions have not been characterized. The purposes of this study
      were to: (1) evaluate the accuracy of a widely used sweat prediction equation
      (SHAP) when widening it's boundaries to include cooler environments (2 h) and
      very prolonged exercise (8 h), (2) determine the independent impact of holding
      skin temperature constant (SHAP36), and (3) describe how adjustments for non
      sweat losses (NSL) and clothing saturation dynamics affect prediction accuracy.
      Water balance was measured in 39 volunteers during 15 trials that included
      intermittent treadmill walking for 2 h (300-600 W, 15-30 degrees C; n=21) or 8 h
      (300-420 W, 20-40 degrees C; n=18). Equation accuracy was assessed by comparing
      actual and predicted sweating rates (211 observations) using least-squares
      regression. Mean and 95% confidence intervals for group differences were compared
      against a zone of indifference (+/-0.125 l/h). Sweating rate variance accounted
      for by SHAP and SHAP36 was always high (r2>0.70), while the standard error of the
      estimate was small and uniform around the line of best fit. SHAP errors were
      >0.125 l/h during 2 and 8 h of exercise. SHAP36 errors were <0.125 l/h for 2 h
      conditions but were higher at 8 h in three of the six warmest trials. Adjustments
      for NSL and clothing saturation dynamics help explain SHAP errors at 2 and 8 h,
      respectively. These results provide a basis for future development of accurate
      algorithms with broader utility.

PMID- 17534644
TI  - Evidence of a contralateral repeated bout effect after maximal eccentric
      contractions.
AB  - The aim of this investigation was firstly, to examine whether a contralateral
      repeated bout effect is manifested after a single bout of maximal eccentric
      muscle actions and secondly, to compare the magnitude of any such protection to
      an ipsilateral control. Sixteen male subjects undertook 45 repetitions of maximal
      eccentric contractions of the elbow flexors. The ipsilateral group (IL, N=8)
      repeated the exercise using the same arm and the contralateral group (CL, N=8)
      repeated the exercise using the contralateral arm 14 days later. Serum creatine
      kinase (CK), muscle soreness, maximal voluntary contraction (MVC) and range of
      motion (ROM) were significantly attenuated in the repeated bout for IL. CL also
      showed a significant reduction in the repeated bout for CK, muscle soreness and
      MVC. Despite the significant attenuation of dependent variables in both groups
      the magnitude of change was less in CL compared to IL for CK, soreness, MVC and
      ROM. The findings demonstrate a repeated bout effect in the contralateral limb
      after a single bout of maximal eccentric exercise; however, the magnitude of
      protection in the contralateral limb is less than that manifested in the
      ipsilateral limb. The apparent contralateral repeated bout effect observed in
      this investigation is thought to be predominantly mediated by neural mechanisms,
      although further research is required to elucidate this possibility.

PMID- 17534646
TI  - Determinants of maximal oxygen uptake in moderate acute hypoxia in endurance
      athletes.
AB  - The factors determining maximal oxygen consumption were explored in eight
      endurance trained subjects (TS) and eight untrained subjects (US) exposed to
      moderate acute normobaric hypoxia. Subjects performed maximal incremental tests
      at sea level and simulated altitudes (1,000, 2,500, 4,500 m). Heart rate (HR),
      stroke volume (SV), cardiac output (.Q), arterialized oxygen saturation (Sa'O2),
      oxygen uptake (.VO2max), ventilation (.VE, expressed in normobaric conditions)
      were measured. At maximal exercise, ventilatory equivalent (.VE/.VO2max), O2
      transport (.QaO2max) and O2 extraction (O2ERmax) were calculated. In TS, .Qmax
      remained unchanged despite a significant reduction in HRmax at 4,500 m. SVmax
      remained unchanged. .VEmax decreased in TS at 4,500 m, .VE/.VO2max was lower in
      TS and greater at 4,500 m vs. sea level in both groups. Sa'O2max decreased at and
      above 1,000 m in TS and 2,500 m in US, O2ERmax increased at 4,500 m in both
      groups. .QaO2max decreased with altitude and was greater in TS than US up to
      2,500 m but not at 4,500 m. .VO2max decreased with altitude but the decrement
      (Delta.VO2max) was larger in TS at 4,500 m. In both groups Delta.VO2max in
      moderate hypoxia was correlated with Delta.QaO2max. Several differences between
      the two groups are probably responsible for the greater Delta.VO2max in TS at
      4,500 m : (1) the relative hypoventilation in TS as shown by the decrement in
      .VEmax at 4,500 m (2) the greater.QaO2max decrement in TS due to a lower Sa'O2max
      and unchanged .Qmax 3) the smaller increase in O2ERmax in TS, insufficient to
      compensate the decrease in .QaO2max.

PMID- 17534647
TI  - Tympanic temperature is not suited to indicate selective brain cooling in humans:
      a re-evaluation of the thermophysiological basics.
AB  - Selective brain cooling in humans, with venous blood returning from the head
      surface as the relevant heat sink, was proposed more than two decades ago as a
      mechanism protecting the brain against damage in hyperthermic conditions. Brain
      cooling was inferred from decreases of tympanic temperature under the premise
      that it reflected brain temperature closely, even in conditions of external head
      cooling. In mammals with a well-developed carotid rete selective brain cooling
      and its quantitative relevance are experimentally well established by directly
      monitoring brain temperature. For humans, however, the dispute about the
      existence and physiological relevance of selective brain cooling has remained
      unsettled, especially, as far as arguments have been exchanged on the basis of
      thermophysiological data and model calculations considering brain metabolism,
      brain hemodynamics and the anatomical preconditions for arterio-venous heat
      exchange. In this essay two seminal studies in support of the existence of human
      selective brain cooling in the condition of exercise hyperthermia, with and
      without dehydration, are re-examined from two points of view: first the
      stringency of the working hypotheses underlying data evaluation and their
      subsequent fate. Second the minimum theoretical requirements for data
      interpretation. The working hypotheses supporting data interpretation in favor of
      selective brain cooling in humans were heuristic and/or had become questionable
      at the dates of their application; today, they may be considered as outdated.
      Data interpretation becomes most conclusive, if tympanic temperature simply is
      not taken into account.

PMID- 17534648
TI  - Learning with incomplete information and the mathematical structure behind it.
AB  - We investigate the problem of learning with incomplete information as exemplified
      by learning with delayed reinforcement. We study a two phase learning scenario in
      which a phase of Hebbian associative learning based on momentary internal
      representations is supplemented by an 'unlearning' phase depending on a graded
      reinforcement signal. The reinforcement signal quantifies the success-rate
      globally for a number of learning steps in phase one, and 'unlearning' is
      indiscriminate with respect to associations learnt in that phase. Learning
      according to this model is studied via simulations and analytically within a
      student-teacher scenario for both single layer networks and, for a committee
      machine. Success and speed of learning depend on the ratio lambda of the learning
      rates used for the associative Hebbian learning phase and for the unlearning
      correction in response to the reinforcement signal, respectively. Asymptotically
      perfect generalization is possible only, if this ratio exceeds a critical value
      lambda( c ), in which case the generalization error exhibits a power law decay
      with the number of examples seen by the student, with an exponent that depends in
      a non-universal manner on the parameter lambda. We find these features to be
      robust against a wide spectrum of modifications of microscopic modelling details.
      Two illustrative applications-one of a robot learning to navigate a field
      containing obstacles, and the problem of identifying a specific component in a
      collection of stimuli-are also provided.

PMID- 17534649
TI  - Branching dendrites with resonant membrane: a "sum-over-trips" approach.
AB  - Dendrites form the major components of neurons. They are complex branching
      structures that receive and process thousands of synaptic inputs from other
      neurons. It is well known that dendritic morphology plays an important role in
      the function of dendrites. Another important contribution to the response
      characteristics of a single neuron comes from the intrinsic resonant properties
      of dendritic membrane. In this paper we combine the effects of dendritic
      branching and resonant membrane dynamics by generalising the "sum-over-trips"
      approach (Abbott et al. in Biol Cybernetics 66, 49-60 1991). To illustrate how
      this formalism can shed light on the role of architecture and resonances in
      determining neuronal output we consider dual recording and reconstruction data
      from a rat CA1 hippocampal pyramidal cell. Specifically we explore the way in
      which an Ih current contributes to a voltage overshoot at the soma.

PMID- 17534650
TI  - Feedback control of the limbs position during voluntary rhythmic oscillation.
AB  - The mechanisms that control the limbs position during rhythmic voluntary
      oscillations were investigated in ten subjects, who were asked to synchronise the
      lower peak of their hand or foot rhythmic oscillations to a metronome beat. The
      efficacy of the "position control" was estimated by measuring the degree of
      synchronisation between the metronome signal and the requested limb position and
      how it was affected by changing both the oscillation frequency (between 0.4 and
      3.0 Hz) and the limbs inertial properties. With the limbs unloaded, the lower
      peak of both the hand and foot oscillations lagged the metronome beat of a slight
      amount that remained constant over the whole frequency range (mean phase delay 
      13.2 degrees for the hand and -4.7 degrees for the foot). The constancy was
      obtained by phase-advancing, at each frequency increment, the electromyogram
      (EMG) activation with respect of the clock beat of the amount necessary to
      compensate for the simultaneous increase of the lag between the EMG and the
      movement, produced by the limb mechanical impedance. After loading of either
      limb, the increase of the oscillation frequency induced larger EMG-movement
      delays and the anticipatory compensation became insufficient, so that the
      movement progressively phase-lagged the clock beat. The above results have been
      accurately simulated by a neural network connected to a pendulum model that
      shared the same mechanical properties of the moving limb. The network compares a
      central command (the intended position) to the actual position of the effector
      and acts as a closed-loop proportional, integrative and derivative controller. It
      is proposed that the synchronisation of rhythmic oscillations of either the hand
      or the foot is sustained by a feed-back control that conforms the position of
      each limb to that encoded in the central voluntary command.

PMID- 17534651
TI  - DWT-CEM: an algorithm for scale-temporal clustering in fMRI.
AB  - The number of studies using functional magnetic resonance imaging (fMRI) has
      grown very rapidly since the first description of the technique in the early
      1990s. Most published studies have utilized data analysis methods based on voxel
      wise application of general linear models (GLM). On the other hand, temporal
      clustering analysis (TCA) focuses on the identification of relationships between
      cortical areas by measuring temporal common properties. In its most general form,
      TCA is sensitive to the low signal-to-noise ratio of BOLD and is dependent on
      subjective choices of filtering parameters. In this paper, we introduce a method
      for wavelet-based clustering of time-series data and show that it may be useful
      in data sets with low signal-to-noise ratios, allowing the automatic selection of
      the optimum number of clusters. We also provide examples of the technique applied
      to simulated and real fMRI datasets.

PMID- 17534652
TI  - Local PIP(2) signals: when, where, and how?
AB  - PIP(2) is a minor phospholipid that modulates multiple cellular processes.
      However, its abundance by mass, like diacylglycerol, is still 20 to 100 times
      greater than the master phospholipid second messenger, PIP(3). Therefore, it is a
      case-by-case question whether PIP(2) is acting more like GTP, in being a cofactor
      in regulatory processes, or whether it is being used as a true second messenger.
      Analysis of signaling mechanisms in primary cells is essential to answer this
      question, as overexpression studies will naturally generate false positives. In
      connection with the possible messenger function of PIP(2), a second question
      arises as to how and if PIP(2) metabolism and signaling may be limited in space.
      This review summarizes succinctly the notable cases in which PIP(2) is proposed
      to function in a localized way and the different mechanistic models that may
      allow it to function locally. In general, drastic restrictions of PIP(2)
      diffusion are required. It is speculated that molecular PIP(2) signaling may be
      possible in the absence of PIP(2) gradients via ternary complexes between PIP(2)
      and two protein partners. That PIP(2) synthesis and hydrolysis might be locally
      dependent on protein-protein interactions, and direct lipid "hand-off" is
      suggested by multiple results.

PMID- 17534653
TI  - Combined effects of reduced connexin 43, depressed active generator properties
      and energetic stress on conduction disturbances in canine failing myocardium.
AB  - To show that reductions in connexin43 (Cx43) can contribute, in association with
      electrophysiological alterations identified from unipolar recordings, to
      conduction disturbances in a realistic model of heart failure, canines were
      subjected to chronic rapid pacing (240/min for 4 weeks) and progressive occlusion
      of the left coronary circumflex artery (LCx) by an ameroid constrictor.
      Alterations identified from 191 epicardial recordings included abrupt activation
      delay, functional block, ST segment potential elevation, and reduced maximum
      negative slope (-dV/dt (max)). The LCx territory was divided into apical areas
      with depressed conduction velocity (LCx1: 0.06 +/- 0.04 m/s, mean +/- SD) and
      basal areas with relatively preserved conduction (LCx2: 0.28 +/- 0.01 m/s).
      Subepicardial Cx43 immunoblot measurements (percent of corresponding healthy
      heart measurements) were reduced in LCx1 ( approximately 40%) and LCx2 (
      approximately 60%). In addition, -dV/dt (max) was significantly depressed (-3.8
      +/- 3.3 mV/ms) and ST segment potential elevated (23.3 +/- 14.6 mV) in LCx1
      compared to LCx2 (-9.5 +/- 3.4 mV/ms and 0.3 +/- 1.4 mV). Anisotropic conduction,
      Cx43 and ST segment potential measurements from the left anterior descending
      coronary artery territory, and interstitial collagen from all regions were
      similar to the healthy. Thus, moderate Cx43 reduction to "clinically relevant"
      levels can, in conjunction with regional energetic stress and depression of
      sarcolemmal active generator properties, provide a substrate for conduction
      disturbances.

PMID- 17534654
TI  - Auditory transduction in the mouse.
AB  - The sensory hair cells of the mammalian cochlea transduce acoustic stimuli into
      auditory nerve activity. The biomechanical and molecular details of hair cell
      mechanotransduction are being acquired at an ever-finer level of resolution. In
      this review, we discuss how selected mouse mutants and transgenic models have
      contributed to, and will continue to shape, our understanding of the molecular
      basis of hair cell mechanotransduction. Functional and structural discoveries
      made originally in hair cells of nonmammalian vertebrates have been further
      pursued in the mouse inner ear, where transgenic manipulation can be applied to
      test molecular mechanisms. Additional insights have been obtained from mice
      bearing mutations in genes underlying deafness in humans. Taken together, these
      studies emphasize the elegance of mechanotransduction, enlarge the team of
      molecular players, and begin to reveal the remarkable adaptations that provide
      the sensitivity and temporal resolution required for mammalian hearing.

PMID- 17534655
TI  - Multiple response codes play specific roles in response selection and inhibition
      under task switching.
AB  - Several task-switch studies show that response category repetition is favorable
      on task repetition trials, but disadvantageous on task switch trials. In the
      present study we investigated how this interaction depends on the type and number
      of involved response categories. In a dual-task number-categorization experiment,
      subjects had to respond to tasks T(1) and T(2) with one of the two fingers of
      their left and right hand, respectively. For one group of participants, the use
      of spatial response categories, and for another group the use of finger-type
      categories was induced. It turned out that the interaction between task switching
      and response category repetition was clearly related to the induced response
      categories, but at the same time, the spatial categories nevertheless also
      affected response selection in the finger-type group. However, these two effects
      were additive. This shows that multiple response codes can simultaneously be
      involved in response selection, but that they affect performance differentially.

PMID- 17534656
TI  - Priming and intrusion errors in RSVP streams with two response dimensions.
AB  - Loach and Mari-Beffa (Vis Cogn, 10:513-526, 2003) observed that a distractor
      stimulus, presented immediately after a behaviorally relevant target stimulus,
      negatively primed a related probe stimulus indicating that the distractor had
      been inhibited. They argued that "post-target inhibition" may be a mechanism for
      preventing interference from temporally proximal stimuli; interference that could
      potentially result in a binding/intrusion error. In order to test this
      hypothesis, the authors carried out two rapid serial visual presentation (RSVP)
      experiments in which participants had to report either the identity (Experiment
      1) or color (Experiment 2) of a target letter surrounded by distractor letters.
      In Experiment 1, a close relationship between priming and errors was observed.
      When a distractor stimulus showed evidence of being inhibited the participant was
      less likely to commit a binding error. The opposite was true when a distractor
      stimulus showed evidence of being facilitated. The results of Experiment 2 showed
      limited evidence of the same relationship.

PMID- 17534657
TI  - FGF9/16/20 and Wnt-5alpha signals are involved in specification of secondary
      muscle fate in embryos of the ascidian, Halocynthia roretzi.
AB  - The tail muscle cells of the ascidian tadpole larva originate from two different
      lineages, the B- (primary) and A- and b- (secondary) line blastomeres of the
      eight-cell stage embryo. The primary muscle cells assume muscle fate cell
      autonomously with the involvement of a localized muscle determinant, macho-1. On
      the other hand, fate determination of secondary muscle cells is a non-cell
      autonomous process that depends on cellular interactions. In this paper, we
      investigated the mechanisms underlying fate specification of secondary muscle
      cells in Halocynthia roretzi. We found that FGF and Wnt5 signals were required.
      In contrast, the Nodal signal, which is required for specification of A-line
      muscle cells in another ascidian, Ciona intestinalis, was not necessary for the
      formation of any secondary muscle cells in Halocynthia embryo. Therefore,
      Halocynthia and Ciona show distinctly different mechanisms for generation of the
      secondary lineages, despite the fact that embryogenesis appears very similar
      between these species. We also found that the mechanisms involved in
      specification of A- and b-line muscle cells were distinct in that the required
      timing of the FGF signal for the A-line muscle cells preceded that for the b
      line. Moreover, the inducer blastomeres for specification of these two lineages
      were different.

PMID- 17534658
TI  - Pneumomediastinum in the neonatal and paediatric intensive care unit.
AB  - The incidence, aetiology and pathophysiology of pneumomediastinum (PM), an
      uncommon and potentially serious disease in neonates and children, were
      evaluated. A retrospective chart review of all patients diagnosed with PM who
      were hospitalised in the intensive care unit of the University Children's
      Hospital Zurich, Switzerland, from 2000 to 2006, was preformed. We analysed the
      incidence, severity and causes of PM and investigated the possible differences
      between neonatal and non-neonatal cases. Seven children and nine neonates were
      identified with PM. All patients had a good outcome. Six cases of PM in the group
      of children older than 4 weeks were deemed to be caused by trauma, infection and
      sports, whereas one case was idiopathic. All nine neonatal cases presented with
      symptoms of respiratory distress. We were able to attribute four cases of
      neonatal PM to pulmonary infection, immature lungs and ventilatory support. Five
      neonatal cases remained unexplained after careful review of the hospital records.
      In conclusion, PM in children and neonates has a good prognosis. Mostly, it is
      associated with extrapulmonary air at other sites. It is diagnosed by chest X-ray
      alone. We identified mechanical events leading to the airway rupture in most
      children >4 weeks of life, whereas we were unable to identify a cause in half of
      the neonates studied (idiopathic PM).

PMID- 17534659
TI  - Central lactic acidosis, hyperventilation, and respiratory alkalosis: leading
      clinical features in a 3-year-old boy with malignant meningeal melanoma.
AB  - Meningeal tumors are extremely rare in children and are diagnostically as well as
      therapeutically challenging. Among the least common types of malignancies in
      childhood is malignant melanoma, counting for less than 1% of pediatric tumors.
      Due to the rarity and the wide spectrum of appearance, initial clinical features
      may be misleading. A 3-year-old boy was referred to our hospital with symptoms of
      hyperventilation, dyspnoea, tachycardia, respiratory alkalosis, inarticulate
      speech, and fatigue. Measurement of pH in cerebrospinal fluid (CSF) yielded
      central lactic acidosis despite alkalosis in peripheral blood. Diagnostic imaging
      procedures as well as histology and immunohistochemistry revealed the diagnosis
      of a malignant meningeal melanoma. We hypothesize that central lactate production
      of the tumor nests might have induced central acidification, thus inducing
      hyperventilation by stimulation of central chemoreceptors. This case is a model
      example of the key role of central pH as an inducer/suppressor of ventilation in
      humans and illustrates the critical importance of central pH for regulating both
      ventilation and acid-base homeostasis. Thus, pH of CSF should be measured
      whenever a malignant brain tumor is suspected.

PMID- 17534661
TI  - Age, severe comorbidity and functional impairment independently contribute to
      poor survival in cancer patients.
AB  - PURPOSE: With the increasing number of elderly patients suffering from cancer,
      comorbidity and functional impairment become common problems in patients with
      cancer. Both comorbidity and functional impairment are associated with a shorter
      survival time in cancer patients, but their independent role has rarely been
      addressed before. METHODS: Within a prospective trial we recruited 427 cancer
      patients, irrespective of age and type of cancer, admitted as inpatients prior to
      the start of chemotherapy. Comorbidity was assessed with the cumulative illness
      rating scale (CIRS-G), functional impairment with WHO performance status (WHO
      PS), basal (ADL) and instrumental (IADL) activities of daily living. RESULTS:
      Median follow-up was 34.2 months. A total, 61.4%. of patients died. Median
      survival time was 21.0 months. Age, kind of tumour (solid vs. haematological),
      treatment approach (non-curative vs. curative), WHO-PS (2-4 vs. 0-1), IADL (<8
      vs. 8), and severe comorbidity (CIRS-level 3-4 vs. none) were significantly
      associated with shorter survival time in univariate analysis. In a multivariate
      Cox-regression-analysis, age (HR 1.019; 95%-CI 1.007-1.032; P=0.003), kind of
      tumour (HR 1.832; 95%-CI 1.314-2.554; P<0.001), WHO-PS (HR 1.455; 95%-CI 1.059
      2.000; P=0.021), and comorbidity level 3-4 (HR 1.424; 95%-CI 1.012-2.003;
      P=0.043) maintained their significant association. CONCLUSIONS: Age, severe
      comorbidity, functional impairment, and kind of tumour are independently related
      to shorter survival time in cancer patients.

PMID- 17534660
TI  - Thy-1 as a potential novel diagnostic marker for gastrointestinal stromal tumors.
AB  - PURPOSE: Only few immunohistochemical markers besides c-kit exist for
      gastrointestinal stromal tumors (GISTs). Thy-1, a cell-surface glycoprotein, is a
      marker for several types of stem cells and particularly for neuronal precursor
      cells. The aim of this study was to determine Thy-1 expression in GISTs.
      MATERIALS AND METHODS: Fifty-seven surgically resected and paraffin-embedded GIST
      samples were analyzed by immunohistochemistry with peroxidase method for Thy-1
      molecule. RESULTS: Thy-1 was detected in the majority of 57 GIST samples (54 out
      of 57 patients, 95%). All samples were c-kit positive and 90% were CD34 positive.
      All three Thy-1 negative samples were CD34 positive, had a low proliferative
      index (Ki-67 <or= 10%) and were located in the upper gastrointestinal tract (one
      in esophagus and two in the stomach). As a tendency, Thy-1 negative patients had
      a better prognosis, although not reaching level of significance due to low
      numbers. CONCLUSIONS: Thy-1 is expressed in the majority of GISTs, suggesting a
      novel, additional standard marker for identifying GIST. Future studies should
      focus on the role of Thy-1 in the pathogenesis of GIST and subsequently on its
      potential to act as a molecular target for adjuvant therapy with new molecular
      antitumor agents.

PMID- 17534662
TI  - New approach for assessing vascular distribution within bone tumors using dynamic
      contrast-enhanced MRI.
AB  - PURPOSE: To differentiate benign from malignant bone tumors by analyzing the
      vascular distribution within bone tumors with dynamic contrast-enhanced MRI.
      METHODS: We studied dynamic contrast-enhanced MRI for 49 bone tumors (22
      malignant and 27 benign tumors). Seven small regions of interest (ROI) were set
      inside the largest portion of each tumor. Four ROI were placed evenly on the
      periphery and three ROI were placed evenly on the line of the longest breadth
      within the tumor. The slope of the curve (%Slope) was calculated on the time
      intensity curves of the whole tumor and of each ROI. The variance values for the
      %Slope of the ROI were calculated to assess the dispersion of the intensity
      change at each ROI within the tumor. RESULTS: Mean value of the %Slopes of whole
      tumor regions for malignant bone tumors (70.4 +/- 60.3%) was significantly higher
      than that for benign bone tumors (37.6 +/- 52.9%) (P = 0.015), although giant
      cell tumor (GCT), a locally aggressive tumor, had a relatively higher %Slope.
      Mean value of the variance of %Slopes for malignant bone tumors (3485.9 +/-
      5942.5) was significantly higher than that for all benign tumors (470.4 +/-
      583.9) (P = 0.012), indicating that the %Slope values of seven ROI within
      malignant bone tumors varied more widely compared with the ROI inside benign bone
      tumors. GCT also demonstrated a lower value. CONCLUSION: Our method of analyzing
      the signal intensity change at seven separate regions that evaluates the vascular
      distribution within a tumor could be a useful tool for differentiating between
      benign and malignant bone tumors.

PMID- 17534664
TI  - Invasive Buddleja davidii allocates more nitrogen to its photosynthetic machinery
      than five native woody species.
AB  - The general-purpose genotype hypothesis and the hypothesis of the evolution of
      invasiveness predict that invasive species are characterized by particular traits
      that confer invasiveness. However, these traits are still not well-defined. In
      this study, ecophysiological traits of eight populations of the invasive shrub
      Buddleja davidii from a wide range of European locations and five co-occurring
      native woody species in Germany were compared in a common garden experiment. We
      hypothesized that the invader has higher resource capture ability and utilization
      efficiency than the natives. No differences were detected among the eight
      populations of B. davidii in any of the traits evaluated, indicating that the
      invader did not evolve during range expansion, thus providing support to the
      general-purpose genotype hypothesis. The invader showed significantly higher
      maximum electron transport rate, maximum carboxylation rate, carboxylation
      efficiency, light-saturated photosynthetic rate (P(max)) and photosynthetic
      nitrogen utilization efficiency (PNUE) than the five natives. Leaf nitrogen
      content was not significantly different between the invader and the natives, but
      the invader allocated more nitrogen to the photosynthetic machinery than the
      natives. The increased nitrogen content in the photosynthetic machinery resulted
      in a higher resource capture ability and utilization efficiency in the invader.
      At the same intercellular CO(2) concentration, P (max) was significantly higher
      in the invader than in the natives, again confirming the importance of the higher
      nitrogen allocation to photosynthesis. The invader reduced metabolic cost by
      increasing the ratio of P (max) to dark respiration rate (R (d)), but it did not
      reduce carbon cost by increasing the specific leaf area and decreasing leaf
      construction cost. The higher nitrogen allocation to the photosynthetic
      machinery, P(max), PNUE and P(max)/R(d) may facilitate B. davidii invasion,
      although studies involving a wide range of invasive species are needed to
      understand the generality of this pattern and to fully assess the ecological
      advantages afforded by these features.

PMID- 17534665
TI  - A keystone ant species promotes seed dispersal in a "diffuse" mutualism.
AB  - In order to understand the dynamics of co-evolution it is important to consider
      spatial variation in interaction dynamics. We examined the relative importance of
      ant activity, diversity and species identity in an ant seed dispersal mutualism
      at local, regional and continental scales. We also studied the determinants of
      seed dispersal rates and dispersal distances at eight sites in the Eneabba
      sandplain (29.63 S, 115.22 E), western Australia to understand local variation in
      seed dispersal rate and distance. To test the generality of the conclusions
      derived from the eight local sites, we established 16 sites along a 1650-km
      transect in western Australia, covering 11 degrees of latitude and a six-fold
      increase in rainfall, at which we sampled the ant assemblage, estimated ant
      species richness and ant activity and observed the removal rate of myrmecochorous
      seeds. We also assessed the importance of ant species identity at a continental
      scale via a review of studies carried out throughout Australia which examined ant
      seed dispersal. Among the eight sandplain shrubland sites, ant species identity,
      in particular the presence of one genus, Rhytidoponera, was associated with the
      most dispersal and above average dispersal distances. At the landscape scale,
      Rhytidoponera presence was the most important determinant of seed removal rate,
      while seed removal rate was negatively correlated with ant species richness and
      latitude. Most ant seed removal studies carried out throughout Australia
      reinforce our observations that Rhytidoponera species were particularly important
      seed dispersers. It is suggested that superficially diffuse mutualisms may depend
      greatly on the identity of particular partners. Even at large biogeographic
      scales, temporal and spatial variation in what are considered to be diffuse
      mutualisms may often be linked to variation in the abundance of particular
      partners, and be only weakly - or negatively - associated with the diversity of
      partners.

PMID- 17534666
TI  - Reno-vascular hypertension in childhood: a nationwide survey.
AB  - Renovascular disease accounts for 8-10% of all cases of paediatric hypertension,
      whereas, in adults, its incidence is approximately 1%. The Turkish Paediatric
      Hypertension Group aimed to create the first registry database for childhood
      renovascular hypertension in Turkey. Twenty of the 28 paediatric nephrology
      centres in Turkey responded to the survey and reported 45 patients (27 girls, 18
      boys) with renovascular hypertension between 1990 and 2005. The age at
      presentation ranged from 20 days to 17 years. The mean blood pressure at the
      diagnosis was 169/110 mmHg. Chief complaints of symptomatic patients were
      headache (38%), seizure (18%), epistaxis (4%), growth retardation (4%), cognitive
      dysfunction (4%), polyuria (2%), palpitation (2%), and hemiplegia (2%).
      Renovascular hypertension was found incidentally in 11 children. The diagnosis of
      renovascular hypertension was established with conventional angiography in 39
      patients, MR angiography in three, CT angiography in two, and captopril
      diethylene triamine penta-acetic acid (DTPA) scintigraphy in one patient. Twenty
      one children had bilateral renal artery stenosis and 24 had unilateral renal
      artery stenosis. Of these, 14 (31%) had fibromuscular dysplasia; 12 (27%)
      Takayasu's arteritis; six (13%) neurofibromatosis; two (5%) Williams syndrome;
      one (2%) Kawasaki disease; one (2%) mid-aortic syndrome; one (2%) extrinsic
      compression to the renal artery, and eight (18%) unspecified bilateral renal
      artery stenosis. Hypertension was controlled with antihypertensive drugs in 17
      patients. Percutaneous transluminal angioplasty (PTRA) or surgery had to be
      performed in 28 patients: PTRA in 16 patients, PTRA + surgery in one patient and
      surgery in 11 patients (four nephrectomies). The importance of vasculitic
      disease, especially Takayasu's arteritis, should not be underestimated in
      children with renovascular hypertension.

PMID- 17534663
TI  - Molecular genetics of human growth hormone, insulin-like growth factors and their
      pathways in common disease.
AB  - The human growth hormone gene (GH1) and the insulin-like growth factor 1 and 2
      genes (IGF1 and IGF2) encode the central elements of a key pathway influencing
      growth in humans. This "growth pathway" also includes transcription factors,
      agonists, antagonists, receptors, binding proteins, and endocrine factors that
      constitute an intrincate network of feedback loops. GH1 is evolutionarily coupled
      with other genes in linkage disequilibrium in 17q24.2, and the same applies to
      IGF2 in 11p15.5. In contrast, IGF1 in 12q22-24.1 is not in strong linkage
      disequilibrium with neighbouring genes. Knowledge of the functional architecture
      of these regions is important for the understanding of the combined evolution and
      function of GH1, IGF2 and IGF1 in relation to complex diseases. A number of
      mutations accounting for rare Mendelian disorders have been described in GH-IGF
      elements. The constellation of genes in this key pathway contains potential
      candidates in a number of complex diseases, including growth disorders, metabolic
      syndrome, diabetes (notably IGF2BP2) cardiovascular disease, and central nervous
      system diseases, and in longevity, aging and cancer. We review these genes and
      their associations with disease phenotypes, with special attention to metabolic
      risk traits.

PMID- 17534667
TI  - Risk factors for hypertension 3 years after renal transplantation in children.
AB  - We performed a case-control study in renal transplant patients between 1998 and
      2003 to identify risk factors for arterial hypertension over the medium term in
      pediatric patients undergoing renal transplantation. Three years after
      transplant, patients were classified into hypertensive or control groups. The
      following risk factors were analyzed: hypertension before transplant, glomerular
      filtration rate at sixth posttransplant month, acute rejection episodes, renal
      artery stenosis, accumulated prednisone and calcineurin inhibitor doses, presence
      of native kidneys, donor type (living or cadaver), body mass index at 1 year
      posttransplant, and glomerular disease as renal insufficiency etiology. Of 161
      transplants, 124 fulfilled the inclusion criteria; 63 were hypertensive, and 61
      were controls. Univariate analysis showed hypertension before transplant (52/63
      vs. 27/61, p < 0.001), glomerulopathies (23/63 vs. 12/61, p = 0.001), glomerular
      filtration rate at 6 months (71 +/- 18 vs, 80 +/- 18 ml/min per 1.73 m(2), p =
      0.003) as risk factors. A tendency to statistical significance was observed with
      regard to body mass index (SDS) in the first year (0.40 +/- 1.10 vs, 0.04 +/-
      1.10, p = 0.072). Multivariate analysis showed statistical significance
      concerning previous hypertension and glomerular filtration rate at 6 months.
      Hypertension before transplant and early graft function are the major risk
      factors for hypertension in the medium term following renal transplant.

PMID- 17534669
TI  - [Back pain. Many questions and still too few answers].

PMID- 17534668
TI  - Promotion of oxidative stress in kidney of rats loaded with cystine dimethyl
      ester.
AB  - Cystinosis is a systemic genetic disease caused by a lysosomal transport
      deficiency accumulating cystine in most tissues. Although tissue damage might
      depend on cystine accumulation, the mechanisms of tissue damage are not fully
      understood. Studies performed in fibroblasts of cystinotic patients and in kidney
      cells loaded with cystine dimethyl ester (CDME) suggest that apoptosis is
      enhanced in this disease. Considering that oxidative stress is a known apoptosis
      inducer, our main objective was to investigate the effects of CDME loading on
      several parameters of oxidative stress in the kidney of young rats. Animals were
      injected twice a day with 1.6 micromol/g body weight CDME and/or 0.26 micromol/g
      body weight cysteamine (CSH) from the 16th to the 20th postpartum day and killed
      after 1 or 12 h. CDME induced lipoperoxidation and protein carbonylation and
      stimulated superoxide dismutase, glutathione peroxidase (GPx), and catalase
      activities, probably through the formation of superoxide anions, hydrogen
      peroxide, and hydroxyl free radicals. Coadministration of CSH, the drug used to
      treat cystinotic patients, prevented, at least in part, those effects, possibly
      acting as a scavenger of free radicals. These results suggest that the induction
      of oxidative stress might be one of the mechanisms leading to tissue damage in
      cystinotic patients.

PMID- 17534670
TI  - Preparing patients for threatening medical treatments: effects of a chemotherapy
      educational DVD on anxiety, unmet needs, and self-efficacy.
AB  - GOALS OF WORK: Based on meta-analyses regarding the preparation of patients for
      potentially threatening medical procedures, a DVD, incorporating behavioral role
      modelling, was developed to prepare patients for chemotherapy and assist them to
      self-manage side effects. It was hypothesized that patients who watched the DVD
      (vs those who did not) would report (1) lower anxiety; (2) higher self-efficacy
      related to coping with treatment side effects; (3) fewer supportive care needs;
      and (4) higher satisfaction with information received. It was further
      hypothesized that these effects would be stronger in those perceiving their
      treatment intent to be curative rather than palliative. MATERIALS AND METHODS:
      Quasi-experimental design using a historical control group was employed.
      Participants were scheduled to receive their first ever chemotherapy treatment.
      Group 1 (usual care; n = 50) was prospectively recruited before the release of
      the DVD and group 2 (DVD plus usual care; n = 50) after the release. Before
      commencing chemotherapy, all patients completed reliable and valid measures of
      self-efficacy, anxiety, and supportive care needs. Data was stratified according
      to perceived treatment intent. Independent sample t tests were performed for each
      group (curative vs palliative). MAIN RESULTS: Significant differences were found
      between the usual care and intervention groups: for self-perceived curative
      patients in relation to self-efficacy for seeking social support (p = 0.044),
      with increased confidence in those watching the DVD, and for self-perceived
      palliative patients in relation to their satisfaction with information about side
      effects (p = 0.026), with increased satisfaction in those watching the DVD.
      Overall, significant differences were found between self-perceived curative vs
      palliative patients on measures of self-efficacy and supportive care needs, with
      self-perceived curative patients reporting more confidence and fewer needs.
      CONCLUSIONS: The educational DVD was considered highly acceptable by patients and
      was found to increase self-efficacy and reduce supportive care needs. Hence, it
      is appropriate to give to patients before face-to-face chemotherapy education.
      Additional pretreatment education is recommended, particularly for self-perceived
      palliative patients, to reduce their pretreatment anxiety and enhance their
      confidence in coping with treatment.

PMID- 17534671
TI  - Incorporation of two modified nucleosides allows selective platination of an
      oligonucleotide making it suitable for duplex cross-linking.
AB  - Platinated oligonucleotides are promising tools for the control of gene
      expression, since they may target and cross-link nucleic acid chains. Here we
      describe a method for the preparation of platinated oligonucleotides that has
      proved able to selectively cross-link complementary sequences, making use of 5
      methylcytidine analogs with thioether or imidazole groups attached to the 4
      position. These nucleoside analogs were derivatized as phosphoramidites and
      introduced in oligonucleotide chains using standard phosphite triester chemistry.
      Different oligonucleotide sequences containing either one or two analogs
      appending from the 5'-end were synthesized and used in preliminary platination
      studies. The reaction of transplatin with oligonucleotides containing the
      thioether-modified nucleobase was fast, but generally afforded unstable adducts
      and complex reaction mixtures. The imidazole-containing oligonucleotides reacted
      with transplatin much more slowly, in particular at slightly basic pH, and it was
      found that the imidazole-modified cytosine was less reactive than the natural
      nucleobases. In contrast, transplatin selectively reacted with the thioether and
      imidazole groups of oligonucleotides containing the two cytosine analogs in
      neighboring positions, even in the presence of the four nucleobases and
      particularly three guanines, affording platinated oligonucleotides suitable for
      cross-linking.

PMID- 17534672
TI  - Albumin-binding PARACEST agents.
AB  - Lanthanide complexes (Eu(3+), Gd(3+) and Yb(3+)) of two different 1,4,7,10
      tetraazacyclododecane-1,4,7,10-tetraacetic acid tetraamide derivatives containing
      two (2) and four (3) O-benzyl-L-serine amide substituents were synthesized and
      their chemical exchange saturation transfer (CEST) and relaxometric properties
      were examined in the presence and absence of human serum albumin (HSA). Both Eu2
      and Eu3 display a significant CEST effect from a single slowly exchanging Eu(3+)
      bound water molecule, making these PARACEST complexes potentially useful as
      vascular MRI agents. Yb2 also showed a detectable CEST effect from both the
      Yb(3+)-bound water protons and the exchangeable NH amide protons, making it
      potentially useful as a vascular pH sensor. Fluorescence displacement studies
      using reporter molecules indicate that both Gd2 and Gd3 displace dansylsarcosine
      from site II of HSA with inhibition constants of 32 and 96 microM, respectively,
      but neither complex significantly displaces warfarin from site I. Water proton
      relaxation enhancements of 135 and 171% were observed upon binding of Gd2 and Gd3
      to HSA, respectively, at 298 K and pH 7.4.

PMID- 17534673
TI  - The field theoretical study of chemical interaction in terms of the Rigged QED:
      new reactivity indices.
AB  - How the mode of bonding affects stability and reactivity of molecule on the frame
      of nonrelativistic limit of the rigged quantum electrodynamics using new indices
      for description of bond properties related to bond orders have been characterized
      here. These indices are in close relation with tensorial interpretation of bond
      that among others allows discriminating covalent bonds using spindle structure
      concept. The real three-dimensional space representation of new interaction
      energy density utilized in this study contribute to better understanding of
      interaction phenomena between atoms and molecules. The differences in reactivity
      and stabilities of molecules have their root in the redistribution of interaction
      energy density.

PMID- 17534674
TI  - Behavioral cues that great apes use to forage for hidden food.
AB  - We conducted three studies to examine whether the four great ape species
      (chimpanzees, bonobos, gorillas, and orangutans) are able to use behavioral
      experimenter-given cues in an object-choice task. In the subsequent experimental
      conditions subjects were presented with two eggs, one of which contained food and
      the other did not. In Study 1 the experimenter examined both eggs by smelling or
      shaking them, but only made a failed attempt to open (via biting) the egg
      containing food. In a control condition, the experimenter examined and attempted
      to open both eggs, but in reverse order to control for stimulus enhancement. The
      apes significantly preferred the egg that was first examined and then bitten, but
      had no preference in a baseline condition in which there were no cues. In Study
      2, we investigated whether the apes could extend this ability to cues not
      observed in apes so far (i.e., attempting to pull apart the egg), as well as
      whether they made this discrimination based on the function of the action the
      experimenter performed. Subjects significantly preferred eggs presented with this
      novel cue, but did not prefer eggs presented with a novel but functionally
      irrelevant action. In Study 3, apes did not interpret human actions as cues to
      food-location when they already knew that the eggs were empty. Thus, great apes
      were able to use a variety of experimenter-given cues associated with foraging
      actions to locate hidden food and thereby were partially sensitive to the general
      purpose underlying these actions.

PMID- 17534675
TI  - Expertise acquisition as sustained learning in humans and other animals:
      commonalities across species.
AB  - Expertise acquisition may be a universal attribute of animals. In this study data
      on foraging efficiency, or expertise, was compared for four species: honeybees
      (Apis mellifera), oystercatchers (Haematopus ostralegus), chimpanzees (Pan
      troglodytes), and humans (Homo sapiens). Polynomial regression models were
      constructed to investigate the relationship between age and foraging efficiency.
      There was a similar expertise-acquisition function between age and foraging
      efficiency across species, best described by a quadratic equation. The peak of
      performance was reached, in all cases, before the average age of death but well
      after reaching physical maturity and the percentage of lifespan devoted to the
      skill was more than 10% of the species-typical lifespan.

PMID- 17534676
TI  - Cost-ineffectiveness of serum vancomycin levels.

PMID- 17534678
TI  - Surveillance of enteroviruses in France, 2000-2004.
AB  - In the context of poliomyelitis eradication, a reinforced sentinel laboratory
      network for surveillance of enteroviruses (RSE) was implemented in France in
      January 2000, and the purpose of this report is to describe the results of the
      five first years of surveillance. From 2000 to 2004, the RSE laboratory network
      performed detailed surveillance of the circulating enteroviruses. No wild-type
      poliovirus was isolated from humans during the 5 years of surveillance, although
      two imported vaccine polioviruses were detected. During the same period, Sabin
      like polioviruses were identified on five occasions in the sludge from sewage
      treatment plants, but no wild-type poliovirus was found. Over the 5 years of
      surveillance, information was collected from 192,598 clinical samples, including
      39,276 cerebrospinal fluid specimens, of which 14.7% were positive for
      enteroviruses, 45,889 stool samples (4.3% positive for enteroviruses), 70,330
      throat swabs (2.2% positive) and 14,243 sera (1.4% positive). The ten main
      nonpolio enteroviruses typed were as follows, in decreasing order of frequency: E
      30, E-13, E-6, CV-B5, E-11, CV-B4, E-9, E-7, CV-B1, and CV-B2. During the year
      2000, an outbreak of aseptic meningitis due to three main enteroviruses
      (echoviruses type 30, 13, and 6) was monitored. Continued surveillance of
      enteroviruses is important to alert physicians and public health officials to
      changes in disease trends. Although the geographical coverage of the RSE network
      as well as the percentage of enteroviruses identified must be improved, the large
      number of samples tested for enteroviruses shows the ability of virology
      laboratories to detect the circulation of enteroviruses and to report the
      possible identification of poliovirus (wild-type, vaccine-derived, or Sabin
      like).

PMID- 17534677
TI  - Monotherapy versus combination antibiotic therapy for patients with bacteremic
      Streptococcus pneumoniae community-acquired pneumonia.
AB  - The purpose of this study was to examine the impact of antimicrobial monotherapy
      vs combination therapy on length of stay and mortality for patients with
      Streptococcus pneumoniae pneumonia. Thirty-nine percent of patients received
      monotherapy, while 61% received combination therapy. Although there was no
      significant difference in mortality (OR 1.25, 95% CI = 0.25-6.8), there was a
      significant increase in length of stay for patients who received combination
      therapy (p = 0.02). Patients with bacteremic pneumococcal pneumonia treated with
      empiric combination therapy had no significant difference in mortality; however,
      they did have increased length of stay after adjusting for severity of illness.
      Randomized controlled trials are needed to determine what is the optimal empiric
      antimicrobial regime for patients with community-acquired pneumonia.

PMID- 17534679
TI  - Classifying torso deformity in scoliosis using orthogonal maps of the torso.
AB  - Analysis of three-dimensional (3D) images of human torsos for torso deformities
      such as scoliosis requires classifying torso distortion. Assessing torso
      distortion from 3D images is not trivial as actual torsos are non-symmetric and
      show an outstanding range of variations leading to high classification errors. As
      the degree of spinal deformity (and classification of torso shape) influences
      scoliosis treatment options, the development of more accurate classification
      procedures is desirable. This paper presents a technique for assessing torso
      shape and classifying scoliosis into mild, moderate and severe categories using
      two indices, 'twist' and 'bend', obtained from orthogonally transformed images of
      the complete torso surface called orthogonal maps. Four transforms (axial line,
      unfolded cylinder, enclosing cylinder and subtracting cylinder) were used. Blind
      tests on 361 computer models with known deformation parameter values show 100%
      classification accuracy. Tests on eight volunteers without scoliosis validated
      the system and tests on 22 torso images of volunteers with scoliosis showed up to
      95.5% classification accuracy. In addition to classifying scoliosis, orthogonal
      maps present the entire torso in one view and are viable for use in scoliosis
      clinics for monitoring the progression of scoliosis.

PMID- 17534680
TI  - Empirical mode decomposition: a method to reduce low frequency interferences from
      surface electroenterogram.
AB  - The surface electroenterogram (EEnG) is a non-invasive method of studying
      myoelectrical bowel activity. However, surface EEnG recordings are contaminated
      by cardiac activity, respiratory and motion artifacts, and other sources of
      interference. The aim of this work is to remove the respiration artifact and the
      very low frequency components from surface EEnG by means of empirical mode
      decomposition (EMD). Eleven recording sessions were carried out on canine model.
      Several parameters were calculated before and after the application of the
      method: signal-to-interference ratio (S/I ratio) and the attenuation level of the
      signal and of interference. The results show that the S/I ratio was significantly
      higher after the application of the method (3.68+/-5.54 dB vs. 10.45+/-3.65 dB),
      the attenuation level of signal and of interference is -0.49+/-0.80 dB versus 
      7.26+/-5.42 dB, respectively. Therefore, EMD could be a useful aid in identifying
      the intestinal slow wave and in removing interferences from EEnG recordings.

PMID- 17534681
TI  - Use of a thin-section archive and enterprise 3-dimensional software for long-term
      storage of thin-slice CT data sets-a reviewers' response.
AB  - Current developments in storage solutions, PACS, and client-server systems allow
      for 3D imaging at the desktop. This can be achieved together with full storage
      into PACS of all slices, including the very large thin-section CT datasets. This
      paper describes a possible setup, which has been in operation for several years
      now, in response to an article by Meenan et al. previously published in this
      journal (1).

PMID- 17534682
TI  - Using applet-servlet communication for optimizing window, level and crop for
      DICOM to JPEG conversion.
AB  - In the creation of interesting radiological cases in a digital teaching file, it
      is necessary to adjust the window and level settings of an image to effectively
      display the educational focus. The web-based applet described in this paper
      presents an effective solution for real-time window and level adjustments without
      leaving the picture archiving and communications system workstation. Optimized
      images are created, as user-defined parameters are passed between the applet and
      a servlet on the Health Insurance Portability and Accountability Act-compliant
      teaching file server.

PMID- 17534683
TI  - RadMonitor: radiology operations data mining in real time.
AB  - This paper describes the web-based visualization interface of RadMonitor, a
      platform-independent web application designed to help manage the complexity of
      information flow within a health care enterprise. The system eavesdrops on Health
      Layer 7 traffic and parses statistical operational information into a database.
      The information is then presented to the user as a treemap--a graphical
      visualization scheme that simplifies the display of hierarchical information.
      While RadMonitor has been implemented for the purpose of analyzing radiology
      operations, its XML backend allows it to be reused for virtually any other
      hierarchical data set.

PMID- 17534684
TI  - The hypoxic environment in tumor-stromal cells accelerates pancreatic cancer
      progression via the activation of paracrine hepatocyte growth factor/c-Met
      signaling.
AB  - BACKGROUND: Pancreatic cancer is one of the representative solid tumors, in which
      the hypoxic microenvironment plays a crucial role in malignant progression. We
      previously demonstrated that tumor-stromal interaction under hypoxia enhances the
      invasiveness of pancreatic cancer cells through hepatocyte growth factor (HGF)/c
      Met signaling. METHODS: We investigated the immunohistochemical expression of
      hypoxia inducible factor-1alpha (HIF-1alpha) c-Met, and HGF in both cancer and
      stromal cells using 41 pancreatic cancer tissue specimens, and tried to identify
      any correlations with the clinical features and survival. RESULTS: Positive
      staining for HIF-1alpha was observed in both pancreatic cancer and the
      surrounding stromal cells in more than 30% of the cases, and it significantly
      correlated with lymph node metastasis (P < .05). A significant correlation was
      observed between the expression of HIF-1alpha and HGF in stromal cells (P < .05).
      In addition, the c-Met expression in cancer cells was found to significantly
      correlate with the HGF expression in not only cancer but also stromal cells. The
      disease-free survival rates of the patients with HIF-1alpha in cancer, stromal, c
      Met in cancer, and an HGF expression in stromal cells was significantly worse
      than those without such expressions (P < .05). CONCLUSIONS: These data suggest
      that the HGF/c-Met signaling via HIF-1alpha ?may therefore negatively affect the
      prognosis in patients with pancreatic cancer, and targeting tumor stroma under
      hypoxia might thus be potentially useful as a novel therapy for this cancer.

PMID- 17534685
TI  - Photodynamic therapy with curative intent for Barrett's esophagus with high grade
      dysplasia and superficial esophageal cancer.
AB  - BACKGROUND: Photodynamic therapy (PDT) has been used to palliate advanced,
      obstructing, or bleeding esophageal cancers (ECs) and Barrett's high-grade
      dysplasia (HGD). Few investigators, though, have described using PDT to cure
      either disease. METHODS: We performed a retrospective review from 1997-2005 of 50
      patients with HGD or EC. All patients refused surgical resection or were
      physiologically unfit. They were instead treated using PDT with curative intent.
      Clinical follow-up, long-term survival, complications, and recurrence were
      evaluated. RESULTS: Thirteen patients (26%) had Barrett's HGD, 6 (12%) had small,
      intramural carcinomas, 16 (32%) had T1 N0 tumors, 14 (28%) had T2 N0 tumors, and
      1 (2%) had a small, polypoid T3 lesion. The mean length of follow-up was 28.1
      months. Sixteen patients (32%) are alive without recurrence, 15 (30%) are living
      with residual or recurrent disease and have received additional PDT, and the
      remainder (38%) died of recurrent EC or other causes and had known recurrence.
      Sixteen (32%) patients received adjuvant chemotherapy, radiation, or both.
      Esophageal stricture occurred in 21 (42%) patients. There was no procedure
      related mortality. CONCLUSIONS: PDT may represent a reasonable alternate to
      esophagectomy for high-risk patients with HGD or superficial esophageal cancer.
      Due to superior survival and local control, we still favor esophagectomy for
      patients without physiologic impairment. However, PDT appears to potentially cure
      approximately one-third of superficial esophageal cancers and provide local
      control of high-grade dysplasia in a similar subset of patients.

PMID- 17534686
TI  - A randomized phase 2 trial of bevacizumab with or without daily low-dose
      interferon alfa-2b in metastatic malignant melanoma.
AB  - BACKGROUND: Vascular endothelial growth factor (VEGF) is a proangiogenic molecule
      produced by melanoma cells. We hypothesized that administration of bevacizumab
      (Bev), a monoclonal antibody that neutralizes VEGF, with low-dose interferon alfa
      2b (IFN-alpha2b), an inhibitor of basic fibroblast growth factor (FGF), would
      lead to the regression of metastatic melanoma. METHODS: Patients with metastatic
      melanoma were randomized to receive Bev (15 mg/kg intravenously every 2 weeks)
      with or without low-dose IFN-alpha2b (1 MU/m2 subcutaneously daily). Patients
      exhibiting a clinical response or stable disease after 12 weeks were treated
      until disease progression. RESULTS: Thirty-two patients (16 per arm) were accrued
      (18 male, 14 female; mean age 57.5 years). Both regimens were well tolerated. Six
      patients developed easily managed exacerbations of preexisting hypertension. Two
      patients developed grade 3 proteinuria that resolved after a treatment break. IFN
      alpha2b therapy was associated with grade 1 to 2 constitutional symptoms.
      Arterial thromboembolic complications were observed in three patients (two mild
      myocardial infarctions, one transient ischemic attack), all of whom had risk
      factors. One patient (Bev plus IFN-alpha2b arm) had locally recurrent scalp
      disease that partially responded to therapy. Eight patients (five Bev, three Bev
      plus IFN-alpha2b) had prolonged disease stabilization (24 to 146 weeks). Plasma
      levels of VEGF and FGF did not correlate with any clinical parameter. The patient
      with the longest period of stable disease had the highest baseline VEGF and FGF.
      CONCLUSIONS: Bev was well tolerated at this dose and prolonged disease
      stabilization was achieved in one-quarter of metastatic melanoma patients. Low
      dose IFN-alpha2b did not augment the activity of Bev.

PMID- 17534687
TI  - Is sentinel node biopsy necessary in conservatively treated DCIS?
AB  - BACKGROUND: We sought to identify the risk of axillary node involvement in
      patients with ductal carcinoma in situ (DCIS) and to determine whether axillary
      node assessment is necessary in these patients. Sentinel node biopsy (SNB) is
      replacing standard axillary lymph node dissection (ALND) for surgical staging of
      invasive breast cancer. Its use in patients with DCIS versus local excision (LE),
      observation, and/or breast irradiation remains in question. METHODS: We examined
      the records of 813 patients with localized DCIS and disease-negative margins
      after LE who were randomly assigned to no further therapy or to breast
      irradiation in National Surgical Adjuvant Breast and Bowel Project (NSABP) trial
      B-17 and 1799 patients randomized to receive placebo or tamoxifen after LE +
      radiotherapy in NSABP trial B-24. An ALND was performed in 253 patients in NSABP
      B-17 and in 162 in NSABP B-24. RESULTS: We found that in NSABP trial B-17, seven
      patients developed ipsilateral nodal recurrence (INR). Overall INR rate was
      0.83/1000 patient-years. In NSABP B-24, overall INR rate was 0.36/1000 patient
      years. INR can be considered a surrogate for axillary involvement at the time of
      DCIS diagnosis. CONCLUSIONS: INR in patients with DCIS treated conservatively is
      extremely rare. Our findings do not support the routine use of SNB in patients
      with conservatively treated, localized DCIS.

PMID- 17534689
TI  - Long-term outcome after resection for chronic pancreatitis in 224 patients.
AB  - INTRODUCTION: Organ complications like biliary or duodenal stenosis as well as
      intractable pain are current indications for surgery in patients with chronic
      pancreatitis (CP). We present here our experience with pancreatic resection for
      CP and focus on the long-term outcome after surgery regarding pain,
      exocrine/endocrine pancreatic function, and the control of organ complications in
      224 patients with a median postoperative follow-up period of 56 months. METHODS:
      During 11 years 272 pancreatic resections were performed in our institution for
      CP. Perioperative mortality was 1%. Follow-up data using at least standardized
      questionnaires were available in 224 patients. The types of resection in these
      224 patients were Whipple (9%), pylorus-preserving pancreato-duodenectomy (PD)
      (PPPD; 40%), duodenum-preserving pancreatic head resection (DPPHR; 41%, 50 Frey,
      42 Beger), distal (9%) and two central pancreatic resections. Eighty-six of the
      patients were part of a randomized study comparing PPPD and DPPHR. The
      perioperative and follow-up (f/up) data were prospectively documented. Exocrine
      insufficiency was regarded as the presence of steatorrhea and/or the need for
      oral enzyme supplementation. Multivariate analysis was performed using binary
      logistic regression. RESULTS: Perioperative surgical morbidity was 28% and did
      not differ between the types of resection. At last f/up 87% of the patients were
      pain-free (60%) or had pain less frequently than once per week (27%). Thirteen
      percent had frequent pain, at least once per week (no difference between the
      operative procedures). A concomitant exocrine insufficiency and former
      postoperative surgical complications were the strongest independent risk factors
      for pain and frequent pain at follow-up. At the last f/up 65% had exocrine
      insufficiency, half of them developed it during the postoperative course. The
      presence of regional or generalized portal hypertension, a low preoperative body
      mass index, and a longer preoperative duration of CP were independent risk
      factors for exocrine insufficiency. Thirty-seven percent of the patients without
      preoperative diabetes developed de novo diabetes during f/up (no risk factor
      identified). Both, exocrine and endocrine insufficiencies were independent of the
      type of surgery. Median weight gain was 2 kg and higher in patients with
      preoperative malnutrition and in patients without abdominal pain. After PPPD, 8%
      of the patients had peptic jejunal ulcers, whereas 4% presented with biliary
      complications after DPPHR. Late mortality was analyzed in 233 patients. Survival
      rates after pancreatic resection for CP were 86% after 5 years and 65% after 10
      years. CONCLUSIONS: Pancreatic resection leads to adequate pain control in the
      majority of patients with CP. Long-term outcome does not depend on the type of
      surgical procedure but is in part influenced by severe preoperative CP and by
      postoperative surgical complications (regarding pain). A few patients develop
      procedure-related late complications. Late mortality is high, probably because of
      the high comorbidity (alcohol, smoking) in many of these patients.

PMID- 17534688
TI  - Improving colorectal cancer screening in primary care practice: innovative
      strategies and future directions.
AB  - Colorectal cancer (CRC) screening has been supported by strong research evidence
      and recommended in clinical practice guidelines for more than a decade. Yet
      screening rates in the United States remain low, especially relative to other
      preventable diseases such as breast and cervical cancer. To understand the
      reasons, the National Cancer Institute and Agency for Healthcare Research and
      Quality sponsored a review of CRC screening implementation in primary care and a
      program of research funded by these organizations. The evidence base for
      improving CRC screening supports the value of a New Model of Primary Care
      Delivery: 1. a team approach, in which responsibility for screening tasks is
      shared among other members of the practice, would help address physicians' lack
      of time for preventive care; 2. information systems can identify eligible
      patients and remind them when screening is due; 3. involving patients in
      decisions about their own care may enhance screening participation; 4. monitoring
      practice performance, supported by information systems, can help target patients
      at increased risk because of family history or social disadvantage; 5.
      reimbursement for services outside the traditional provider-patient encounter,
      such as telephone and e-mail contacts, may foster enhanced screening delivery; 6.
      training opportunities in communication, cultural competence, and use of
      information technologies would improve provider competence in core elements of
      screening programs. Improvement in CRC screening rates largely depends on the
      efforts of primary care practices to implement effective systems and procedures
      for screening delivery. Active engagement and support of practices are essential
      for the enormous potential of CRC screening to be realized.

PMID- 17534690
TI  - Homotypic interactions among bacteriophage phiKMV early proteins.
AB  - Little is known about the bacteriophage proteins expressed immediately after
      infection of the host cell. Most of these early proteins are probably involved in
      bacteriophage-host interactions redirecting the bacterial metabolism to phage
      production. Interaction analysis of the first 16 phiKMV gene products (gp)
      identified homotypic interactions of gp7, gp9 and gp15. Two related yeast two
      hybrid procedures, a matrix and a minilibrary approach, were applied to detect
      protein-protein interactions. A two-step selection procedure enabled drastic
      reduction of the background. Interactions were confirmed by drop tests.
      Multimerization of gp15 is consistent with its putative function as a DNA
      helicase involved in DNA replication. Homotypic interaction of gp7 and gp9
      suggests they function as dimers or multimers. The absence of heterotypic
      interactions among early phiKMV proteins hints at their functional independence
      from other early phage proteins and their involvement in phage-host interactions
      that are important for creating optimal conditions for phage propagation.
      Besides, these results demonstrate the compatibility of phiKMV early gene
      products with the yeast two-hybrid system. Therefore, they are promising
      candidates to screen for interactions with host proteins.

PMID- 17534691
TI  - Salt impact on photosynthesis and leaf ultrastructure of Aeluropus littoralis.
AB  - The effects of salinity (400 mM NaCl) on growth, biomass partitioning,
      photosynthesis, and leaf ultrastructure were studied in hydroponically grown
      plants of Aeluropus littoralis (Willd) Parl. NaCl produced a significant
      inhibition of the main growth parameters and a reduction in leaf gas exchange
      (e.g. decreased rates of photosynthesis and stomatal conductance). However, NaCl
      salinity affected neither the composition of photosynthesis pigments nor leaf
      water content. The reduction in leaf gas exchange seemed to correlate with a
      decrease in mesophyll thickness as well as a severe disorganisation of
      chloroplast structure, with misshapen chloroplasts and dilated thylakoid
      membranes. Conspicuously, mesophyll chloroplasts were more sensitive to salt
      treatment than those of bundle sheath cells. The effects of NaCl toxicity on leaf
      structure and ultrastructure and the associated physiological implications are
      discussed in relation to the degree of salt resistance of A. littoralis.

PMID- 17534692
TI  - New evidence of reproductive organs of Glossopteris based on permineralized
      fossils from Queensland, Australia. I. Ovulate organ Homevaleia gen. nov.
AB  - This study describes Homevaleia gouldii H. Nishida, Pigg, Kudo et Rigby gen. et
      sp. nov., an ovule-bearing glossopterid organ, based on a combination of recently
      collected permineralized specimens from the Late Permian Homevale Station
      locality in the Bowen Basin of Queensland, Australia, and on previously studied
      material from the 1977 Gould and Delevoryas study. Homevaleia, which resembles
      the compression-impression genus Dictyopteridium, is an inrolled megasporophyll
      with a distinct keel that bears numerous (over 70) stalked ovules on its adaxial
      surface. Ovules are small, oval, with an elaborate mesh-like structure that is
      developed from the outermost integumentary layers. Specimens interpreted as
      representing different developmental stages show there is an apparent
      interrelationship between megagametophyte development and the opening of the
      surrounding fertile structure for pollination. Together, new information provided
      by this material enables better understanding of glossopterid reproductive
      structure and its function in one distinctive form.

PMID- 17534693
TI  - The distributions of howling monkeys (Alouatta pigra and A. palliata) in
      southeastern Mexico and Central America.
AB  - We compared the distributions of Alouatta palliata and A. pigra in southeastern
      Mexico and Central America with geographic and ecological features to infer
      current barriers and ecological preferences. Distribution data were obtained from
      museum specimen localities, study sites, historic records and field surveys and
      integrated into digital elevation and ecosystem maps using GIS. A. pigra
      evidently occurs at a number of sites above 2,000 m, where temperatures can even
      drop below zero on some days of the year, thus indicating a broader ecological
      tolerance than previously reported. Both species occupy a number of vegetation
      types and can be found in seasonal and nonseasonal forests. We identified the
      highland massif of northern Central America and its associated coniferous and
      subalpine vegetation as a geographic barrier that separates the species. In the
      past, distribution maps for these species have indicated adjacent contiguous
      ranges, but we propose that they are largely separated by these mountains. There
      are two contact zones: a broad area of sympatry north of the highland massif in
      Mexico and a narrow zone in eastern Guatemala where parapatry is maintained by a
      river barrier and where only A. pigra occurs in the high elevations and cooler
      habitats inland. We explore an alternative biogeographic scenario for the split
      of the two species that accounts for the current distribution and differences in
      elevation and cold tolerances.

PMID- 17534694
TI  - Non-invasive low frequency vibration as a potential emergency adjunctive
      treatment for heart attack and stroke. An in vitro flow model.
AB  - BACKGROUND: Myocardial infarction and stroke (arterial thrombosis) comprise the
      leading killers and sources of disability in the developed world, and incomplete
      thrombolysis along with high bleeding rates (plus late presentations to cathlabs)
      have prompted an intensive search for alternative or adjunctive emergency
      therapies. Transcutaneous ultrasound has been studied in remediation of
      thrombosis, but has been problematic due to poor penetration, risk of arterial
      damage, plus the apparent need for a highly skilled approach. Surprisingly there
      has been no reported studies on the much simpler application of transcutaneous
      low frequency vibration (well known for its superior penetration and flow
      enhancing characteristics) to assist arterial thrombolysis. The aim of our
      experiment therefore was to test the hypothesis whether vibration (i.e.
      approximately 100 Hz, 0.5 mm), when applied across an attenuating barrier, would
      assist recanulization of a thrombosed flow system held at arterial like pressure.
      METHODS: A teddy bear with a 2 cm slab of New York Steak placed upon its chest
      surface was used as a test subject with an in-dwelling catheter (approximately
      4.0 mm lumen) cannulated through the bear's thorax. In a series of test runs
      (n=30), a 2 h old (or older) blood clot was injected into the catheter such as to
      occlude it at a stenosis site (approximately 90% luminal narrowing) created by a
      clamp placed along the catheter within the teddy's chest region. A pressurized
      heparinized IV system was in all cases connected to the catheter such as to yield
      an "arterial like" lumen pressure proximal the obstruction. For each test run,
      after a twenty minute observation period to confirm stability of the occlusion,
      test groups where randomized to receive vibration to the slab of steak upon the
      teddy's "chest wall" (generally overlying the site of the thrombotic
      obstruction), or no vibration for an evaluation period of up to 45 min. RESULTS:
      Catheter reflow occurred rapidly (median reflow-time 90 s) in the vibration
      groups within the evaluation period (i.e. 15/17), while the system remained
      otherwise blocked in the control groups receiving no vibration (i.e. 0/13). The
      difference in flow system patency rate for the vibration groups vs. the control
      groups was statistically significant (P=0.0000009). CONCLUSIONS: The frequent and
      generally rapid re-establishment of flow in vibration groups compared to the
      complete absence of reflow in control groups confirms the hypothesis that
      vibration applied across a physical barrier assists clearance of a blood clot in
      a stenosed flow system under systemic levels of pressure. We studied the
      incidence of clearance of a blood clot within a stenosed, heparanized catheter
      system held at arterial like pressure that was treated with externally delivered
      low frequency vibration (applied proximate the thrombotic occlusion across an
      attenuating medium--a 2 cm thick slab of New York Steak--at approximately 100 Hz,
      0.5 mm), versus no vibration. Reflow in test runs incorporating vibration
      occurred faster, and resulted in significantly greater recanulization rates in
      the catheter system versus test runs without vibration (P=0.0000009). Non
      invasive vibration holds potential as an adjunct to pharmacologic therapy in
      treatment of acute arterial thrombosis. Further study of this technique appears
      warranted in live animal models.

PMID- 17534695
TI  - Pulmonary embolism after brain hemorrhage in a hypertensive patient: the
      therapeutic dilemma.
AB  - Massive pulmonary embolism is a life-threatening condition to be treated with
      anticoagulants or even thrombolytic agents in selected cases. However, these
      drugs are controindicated after a recent hemorrhagic episode. We report the case
      of a 46-year-old patient with uncontrolled systemic hypertension who was affected
      by severe spontaneous cerebral hemorrhage and left hemiparesis. After some days
      of rehabilitation care he developed sudden dyspnea, tachycardia and hypotension
      secondary to bilateral pulmonary embolism. Owing to controindication to the use
      of thrombolytic agents, anticoagulant therapy with high-dose intravenous
      unfractionated heparin followed by oral warfarin was begun, with a successful and
      uncomplicated outcome. The therapeutic approach to similar not uncommon cases is
      debated and some hypotheses are made about the aetiology of pulmonary embolism in
      these patients.

PMID- 17534696
TI  - Radiosensitization by diospyrin diethylether in MCF-7 breast carcinoma cell line.
AB  - The development of radio-resistant tumor cells might be overcome by the use of
      tumor selective cytotoxic agents in combination with radiation treatment of
      cancer. Thus, we are exploring the radiomodifying potential of D7, a tumor
      inhibitory compound derived from a plant product, diospyrin, in breast carcinoma
      cells, MCF-7. The present study indicated that D7 could enhance the radiation
      induced cytotoxicity and apoptosis through down-regulation of the anti-apoptotic
      Bcl-2 and COX-2 gene expression, and up-regulation of pro-apoptotic genes, like
      p53 and p21. The higher expression of PUMA, a pro-apoptotic protein was also
      observed in the combination treatment. Effect of D7 on up-regulation of p21
      expression in irradiated MCF-7 cells was concomitant with the cell cycle arrest
      in the G1 phase. Thus, it was concluded that D7 could sensitize the effect of
      radiation in breast carcinoma by regulating the gene expression involved in cell
      cycle and apoptosis.

PMID- 17534697
TI  - CTRP3/cartducin promotes proliferation and migration of endothelial cells.
AB  - CTRP3/cartducin, a novel secretory protein, is a member of the C1q and tumor
      necrosis factor (TNF)-related protein (CTRP) superfamily. CTRP3/cartducin gene is
      transiently up-regulated in a balloon-injured rat carotid artery tissue. In this
      study, we report a new function of CTRP3/cartducin as a regulator of angiogenic
      processes. CTRP3/cartducin promoted proliferation and migration of mouse
      endothelial MSS31 cells in a dose-dependent manner. Further, stimulation of MSS31
      by CTRP3/cartducin led to activation of extracellular signal-regulated kinase 1/2
      (ERK1/2) and p38 mitogen-activated protein kinase (MAPK). MAPK/ERK kinase 1/2
      (MEK1/2) inhibitor, U0126, and p38 MAPK inhibitor, SB203580, blocked the
      CTRP3/cartducin-induced cell proliferation, and migration was blocked by U0126,
      but not the SB203580. Taken together, these results suggest that CTRP3/cartducin
      may be involved as a novel angiogenic factor in the formation of neointima
      following angioplasty.

PMID- 17534698
TI  - cDNA microarray analysis of cyclosporin A (CsA)-treated human peripheral blood
      mononuclear cells reveal modulation of genes associated with apoptosis, cell
      cycle regulation and DNA repair.
AB  - Cyclosporin A (CsA) is a potent immunosuppressant that has been extensively used
      to attenuate patient immune response following organ transplantation. The
      molecular biological mechanism of CsA has been extensively investigated in human
      T cells, and it has been shown to involve modulation of the intracellular
      calcineurin pathway. However, it is plausible that this chemical
      immunosuppressant certainly up- or down-regulate many other biochemical pathways
      of immune cells. In the present study, we used the cDNA microarray method to
      characterize the gene expression profile of human peripheral blood mononuclear
      cells (PBMC) treated in vitro with CsA and controls. The CsA treated PBMC
      displayed statistically significant induction of genes involved in the control of
      cell-cycle regulation (TRRAP), apoptosis/DNA repair (PRKDC, MAEA, TIA1), DNA
      metabolism/response to DNA damage stimulus (PRKDC, FEN1), transcription (NR4A2,
      THRA) and cell proliferation (FEN1, BIN1), whose data have permitted
      identification of target genes involved in CsA immunosuppression.

PMID- 17534700
TI  - Synergistic effect of TRM2/RNC1 and EXO1 in DNA double-strand break repair in
      Saccharomyces cerevisiae.
AB  - In our recently published study, we provided in vitro as well as in vivo data
      demonstrating the involvement of TRM2/RNC1 in homologous recombination based
      repair (HRR) of DNA double strand breaks (DSBs), in support of such claims
      reported earlier. To further validate its role in DNA DSB processing, our present
      study revealed that the trm2 single mutant displays higher sensitivity to
      persistent induction of specific DSBs at the MAT locus by HO-endonuclease with
      higher sterility rate among the survivors compared to wild type (wt) or exo1
      single mutants. Intriguingly, both sensitivity and sterility rate increased
      dramatically in trm2exo1 double mutants lacking both endo-exonucleases with a
      progressively increased sterility rate in trm2exo1 double mutants with short
      induction periods, reaching a very high level of sterility with persistent DSB
      inductions. Mutation analysis of the mating type (MAT) locus among the sterile
      survivors with persistent HO-induction in trm2 and exo1 single mutants as well as
      in trm2exo1 double mutants revealed a similar small insertions and deletions
      events, characteristic of non-homologous end joining (NHEJ) that might have
      occurred due to the lack of proper processing function in these mutants. In
      addition, trm2ku80 and trm2rad52 double mutants also displayed significantly
      higher sterility with persistent DSB induction compared to ku80 and rad52 single
      mutants, respectively, exhibiting a mutation spectra that shifted from base
      substitution (in ku80 and rad52 single mutants) to small insertions and deletions
      in the double mutants (in trm2ku80 and trm2rad52 mutants). These data indicate a
      defective processing in absence of TRM2, with a synergistic effect of TRM2, and
      EXO1 in such processing.

PMID- 17534699
TI  - Effect of hepatocyte growth factor (HGF) on the level of Survivin & XIAP
      expression in several human cancer cell lines, after treating with DNA damaging
      agent.
AB  - Hepatocyte growth factor (HGF) has opposite biological activities in regulating
      apoptosis, also underlying molecular mechanisms are not clearly defined. We
      investigated HGF ability to inhibit cell death, which was induced by Doxorubicin,
      a DNA damaging agent. Also Survivin and XIAP mRNA levels were compared in HGF
      treated and non-treated cells. Cell proliferation and death were assessed using
      MTT assay and dye exclusion tests. Quantitative real-time PCR was used to
      evaluate Survivin and XIAP expression levels after treatment with HGF. ELISA was
      performed to quantify HGF secretion in the selected cancer cell lines media. HGF
      appeared to have inhibitory effect on Doxorubicin induced cell death in all of
      the studied cell lines. It had minimal effect on XAIP and Survivin expression
      levels in MRC-5, MOLT-4 and AGS cell lines; except for XIAP expression level in
      AGS cell line, which was increased substantially after treatment. Surprisingly,
      in KG-1 cell line, XIAP and Survivin expression levels were significantly reduced
      after HGF treatment. Although several members of IAP gene family are reported to
      play role in HGF mediated cytoprotective pathway, we showed that XIAP and
      Survivin do not seem to be involved.

PMID- 17534701
TI  - Characterization of the biochemical and biophysical properties of the
      phosphatidylserine receptor (PS-R) gene product.
AB  - The PS-R gene product was originally described as a cell surface receptor that
      interacts with externalized phosphatidylserine (PS) on apoptotic cells, but more
      recent studies have shown that it plays a critical role in organ development and
      terminal differentiation of many cell types during embryogenesis. Despite these
      important developmental functions, the biochemical and molecular properties of PS
      R are poorly understood. Here we have used several approaches to show that PS-R
      undergoes processive post-translational protein cross-linking to form covalent
      multimers within the nuclear compartment. Although PS-R has a potential Glu-Glu
      (QQ) duet that is often targeted by transglutaminase TG-2, the oligomerization of
      PS-R was not effected by QQ-->AA mutation, or when PS-R gene product was
      expressed in TG-2 (-/-) fibroblasts. Pulse-chase experiments with (35) S
      methionine indicates that the PS-R undergoes an initial proteolytic cleavage,
      followed by progressive multimerization of the monomeric subunits over time. In
      summary, we report here that PS-R is modified by an unusual post-translational
      modification, and we speculate that homomultimer of PS-R might be playing an
      important function as a scaffolding protein in the nucleus.

PMID- 17534702
TI  - Evaluation of a short-form functional capacity evaluation: less may be best.
AB  - PURPOSE: Functional Capacity Evaluation (FCE) contributes to clinical decisions
      regarding fitness-for-work and may improve return-to-work outcomes. However, FCE
      is a burdensome clinical tool in terms of time and cost. We evaluated the
      effectiveness of a short-form FCE protocol. METHODS: A cluster randomized
      controlled trial was conducted. Data were collected on all claimants undergoing
      FCE at Alberta's workers' compensation rehabilitation facility. Twenty-three
      clinicians who were trained and experienced with FCE were randomized to either an
      intervention or control group. The intervention group was trained to conduct
      short-form FCE and used this protocol through the trial's duration, while the
      control group continued standard FCE procedures. Data on subject characteristics,
      administrative outcomes (days to suspension of time loss benefits, days to claim
      closure, and future recurrence) and claimant satisfaction were extracted from the
      WCB-Alberta computer databases. Clinicians logged time taken to complete
      assessments. Analysis included examining differences between groups using
      independent samples t tests, Cox and logistic regression. RESULTS: Subjects
      included 372 claimants of whom 173 were tested with short-form FCE. Subjects were
      predominantly employed (64%) males (69%) with chronic musculoskeletal conditions
      (median duration 252 days). Administrative recovery outcomes were similar between
      groups as were claimant satisfaction ratings. No statistically significant or
      clinically relevant differences were observed on these outcomes between groups. A
      43% reduction in functional assessment time was seen. CONCLUSION: A short-form
      FCE appears to reduce time of assessment while not affecting recovery outcomes
      when compared to standard FCE administration. Such a protocol may be an efficient
      option for therapists performing fitness-for-work assessments.

PMID- 17534703
TI  - Social defeat and the culture of chronicity: or, why schizophrenia does so well
      over there and so badly here.
AB  - The history of the way schizophrenia has been conceptualized in American
      psychiatry has led us to be hesitant to explore the role of social causation in
      schizophrenia. But there is now good evidence for social impact on the course,
      outcome, and even origin of schizophrenia, most notably in the better prognosis
      for schizophrenia in developing countries and in the higher rates of
      schizophrenia for dark-skinned immigrants to England and the Netherlands. This
      article proposes that "social defeat" may be one of the social factors that may
      impact illness experience and uses original ethnographic research to argue that
      social defeat is a common feature of the social context in which many people
      diagnosed with schizophrenia in America live today.

PMID- 17534704
TI  - High macrophage migration inhibitory factor levels in disseminated intravascular
      coagulation patients with systemic inflammation.
AB  - To determine the relationship between macrophage migration inhibitory factor
      (MIF) and disseminated intravascular coagulation (DIC) in patients with systemic
      inflammatory response syndrome (SIRS) and sepsis, and their relationship to
      multiple organ dysfunction syndrome (MODS) and prognosis, we conducted a
      prospective cohort study. Forty-eight patients with SIRS or sepsis were
      classified as 20 DIC and 28 non-DIC patients. MIF, tumor necrosis factor-alpha
      (TNF-alpha), soluble fibrin, protein C activity (protein C), and plasminogen
      activator inhibitor-1 (PAI-1) were all measured within 24 h after the patients
      met the criteria of SIRS or sepsis (day 0), and on days 1 to 4. The number of
      SIRS criteria that the patients met and the DIC scores were determined
      simultaneously. In DIC patients, significantly higher levels of MIF, TNF-alpha,
      soluble fibrin, PAI-1 were found compared with non-DIC patients. We also found
      significantly lower protein C levels in the DIC patients than in the non-DIC
      patients. Significant correlations were found between the peak levels of MIF and
      soluble fibrin in the DIC patients (rs = 0.496, p < 0.0407). All DIC patients had
      MODS and also showed a higher number of dysfunctioning organs and a poorer
      prognosis than the non-DIC patients. A simple logistic regression analysis showed
      the peak MIF levels and DIC significantly to be related to the patients' death
      (odds ratio 1.016 and 40.5; p < 0.0409, p < 0.0009, respectively). In conclusion,
      DIC patients with elevated levels of MIF and TNF-alpha had more organ
      dysfunctions leading to a poor prognosis in a population of SIRS and sepsis
      patients. MIF may therefore play a role in the inflammatory and thrombotic
      processes in DIC patients.

PMID- 17534705
TI  - Percutaneous epicardial ablation reverses ventricular tachycardia mediated
      cardiomyopathy.
AB  - We report on the case of an 18-year-old girl with asymptomatic incessant
      ventricular tachycardia. Initial attempts at endocardial ablation failed and she
      was monitored until her cardiac function deteriorated. A percutaneous epicardial
      approach with electroanatomical mapping was then used which successfully
      terminated the tachycardia. Left ventricular size and function subsequently
      returned to normal. This case demonstrates that percutaneous epicardial ablation
      of ventricular tachycardia is safe and feasible in young patients and highlights
      the importance of recognising this at an early stage.

PMID- 17534706
TI  - Spike-frequency adaptation generates intensity invariance in a primary auditory
      interneuron.
AB  - Adaptation of the spike-frequency response to constant stimulation, as observed
      on various timescales in many neurons, reflects high-pass filter properties of a
      neuron's transfer function. Adaptation in general, however, is not sufficient to
      make a neuron's response independent of the mean intensity of a sensory stimulus,
      since low frequency components of the stimulus are still transmitted, although
      with reduced gain. We here show, based on an analytically tractable model, that
      the response of a neuron is intensity invariant, if the fully adapted steady
      state spike-frequency response to constant stimuli is independent of stimulus
      intensity. Electrophysiological recordings from the AN1, a primary auditory
      interneuron of crickets, show that for intensities above 60 dB SPL (sound
      pressure level) the AN1 adapted with a time-constant of approximately 40 ms to a
      steady-state firing rate of approximately 100 Hz. Using identical random
      amplitude-modulation stimuli we verified that the AN1's spike-frequency response
      is indeed invariant to the stimulus' mean intensity above 60 dB SPL. The transfer
      function of the AN1 is a band pass, resulting from a high-pass filter (cutoff
      frequency at 4 Hz) due to adaptation and a low-pass filter (100 Hz) determined by
      the steady-state spike frequency. Thus, fast spike-frequency adaptation can
      generate intensity invariance already at the first level of neural processing.

PMID- 17534707
TI  - Orgasm as a post-copulatory display.

PMID- 17534708
TI  - Age-dependent stability of sensorimotor functions in the life-extended Drosophila
      mutant methuselah.
AB  - Methuselah is a Drosophila mutant with a 35% increased lifespan. We examined the
      robustness of methuselah's sensorimotor abilities in tethered flight as a
      function of age in experiments designed to test visuomotor synchronization and
      phototaxis in simulated flight. A total of 282 flies from different age groups (4
      hours to 70 days) and genotypes (mth and w1118) were individually tethered under
      an infrared laser-sensor system that digitally recorded wing-beat frequency
      (WBF). We found that mth has a higher average WBF throughout most of its lifespan
      compared to parental control flies (w1118) and develops flight ability at a
      younger age. Its WBF at late life, however, is not significantly different than
      that of its parental control line. We further found that mth entrains during
      flight to motion of a visual grating significantly better than its parental line.
      These findings suggest that the mth gene not only delays chronological aging but
      enhances sensorimotor abilities critical to survival during early and middle, but
      not late life.

PMID- 17534709
TI  - Variance decomposition using an IRT measurement model.
AB  - Large scale research projects in behaviour genetics and genetic epidemiology are
      often based on questionnaire or interview data. Typically, a number of items is
      presented to a number of subjects, the subjects' sum scores on the items are
      computed, and the variance of sum scores is decomposed into a number of variance
      components. This paper discusses several disadvantages of the approach of
      analysing sum scores, such as the attenuation of correlations amongst sum scores
      due to their unreliability. It is shown that the framework of Item Response
      Theory (IRT) offers a solution to most of these problems. We argue that an IRT
      approach in combination with Markov chain Monte Carlo (MCMC) estimation provides
      a flexible and efficient framework for modelling behavioural phenotypes. Next, we
      use data simulation to illustrate the potentially huge bias in estimating
      variance components on the basis of sum scores. We then apply the IRT approach
      with an analysis of attention problems in young adult twins where the variance
      decomposition model is extended with an IRT measurement model. We show that when
      estimating an IRT measurement model and a variance decomposition model
      simultaneously, the estimate for the heritability of attention problems increases
      from 40% (based on sum scores) to 73%.

PMID- 17534712
TI  - A test of three alternative hypotheses regarding the effects of early delinquency
      on adolescent psychosocial functioning and substance involvement.
AB  - This study compared alternative hypotheses (from general deviance, life course,
      and developmental psychopathology perspectives) regarding the effects of early
      adolescent delinquency on psychosocial functioning in family, school, and peer
      contexts, and on alcohol use. Analyses also examined parent-child negative
      affective quality, prosocial school orientation, and peer substance use as
      possible direct predictors of problem substance use. Participants in this
      longitudinal study, extending from age 11 to age 18, were 429 rural teens (222
      girls) and their families. Path model comparisons supported the tenability of a
      partial mediation model that included mediating pathways and a direct effect of
      delinquency on alcohol use, as hypothesized by developmental psychopathology. A
      supplemental analysis controlling for the stability of the family, school, and
      peer variables revealed that delinquency had less pervasive direct effects on,
      and a nonsignificant indirect effect through, changes in the mediators over time.
      Results also showed that peer substance use was a direct positive predictor of
      problem use.

PMID- 17534713
TI  - Unguided clinical and actuarial assessment of re-offending risk: a direct
      comparison with sex offenders in Denmark.
AB  - Meta-analyses suggest that actuarial risk assessments outperform unguided
      clinical judgment for prediction of recidivism in criminal offenders. However,
      there is a lack of direct comparisons of the predictive accuracy of clinical
      judgment and actuarial risk scales for sexual offenders. We followed up 121 male
      sex offenders (> or =18 years) subjected to pre-trial forensic psychiatric
      assessment in Denmark in 1978-1992 (mean post-detainment time = 16.4 years) to
      compare the predictive validity of unstructured clinical judgment of recidivism
      risk with that of the well-established Static-99 (Hanson and Thornton, Law and
      Human Behavior 24:119-136, 2000) and an extension of the Static-99, the Static
      2002 (Hanson and Thornton, Notes on the development of Static-2002 (Rep. No. 2003
      01), Public Safety and Emergency Preparedness Canada, Ottawa, Canada, 2003). The
      predictive accuracy of unguided judgment did not exceed chance for any sexual,
      severe sexual or any violent (sexual or non-sexual) reconviction (AUCs of the ROC
      curve = 0.52, 95%CI = 0.41-0.63; 0.50, 95%CI = 0.34-0.67; and 0.57, 95%CI = 0.40
      0.73, respectively). In contrast, all three outcomes were predicted significantly
      better than chance by the Static-99 (AUC = 0.62, 95%CI = 0.52-0.72; 0.72, 95%CI =
      0.59-0.84; and 0.71, 95%CI = 0.56-0.86) and the Static-2002 (AUC = 0.67, 95%CI =
      0.57-0.77; 0.69, 95%CI = 0.56-0.83; and 0.70, 95%CI = 0.55-0.86). Static-99
      outperformed clinical judgment for sexual recidivision (chi(2) = 5.11, df = 1, p
      < .05). The Static-2002 was significantly more accurate for the prediction of any
      sexual recidivism as compared to unguided clinical judgment but its advantage
      fell just short of statistical significance for severe sexual recidivism (chi(2)
      = 3.56, df = 1, p = 0.06). When tested for recidivism within 2 years, none of the
      three prediction methods yielded results significantly better than chance for any
      outcome. This direct trial of the unguided clinical method argues against its
      continued use for risk assessment of sexual offenders.

PMID- 17534711
TI  - Sequelae of aggression in acutely suicidal adolescents.
AB  - The consequences of aggression on problem course and suicide risk were examined
      in 270 acutely suicidal adolescents (ages 12-17 years; 184 girls). Participants
      were assessed during psychiatric hospitalization (T1), 6-months post
      hospitalization (T2), and 15 or more months post-hospitalization (T3). Study
      variables included self- and parent-reported aggression; self-reported
      internalizing symptoms, suicidal ideation, suicide attempt, and adverse events;
      and clinician-rated suicidal behavior. Aggression was not directly related to
      suicide attempt concurrently or prospectively. However, among more aggressive
      youth, internalizing symptoms were more predictive of T3 suicide attempt than
      among less aggressive youth. T1 aggression predicted aggressive incidents and the
      likelihood of incarceration prior to T3. Two-level hierarchical linear modeling
      indicated that self-reported aggression and internalizing problems were linked in
      terms of severity and rates of decline over time. Overall, parent-reported
      aggression was negatively associated with suicidal ideation. Findings highlight
      (a) the continuity and consequences of aggression, (b) a possible role of
      aggression in worsening suicide risk factors and potentiating suicide attempt,
      and (c) the importance of ongoing research on subtypes of suicidal adolescents.

PMID- 17534714
TI  - Denial predicts recidivism for some sexual offenders.
AB  - This study examined whether there were variables that moderated the relationship
      between denial and recidivism among adult male sexual offenders. The first study
      (N = 489) found that the relationship with sexual recidivism was moderated by
      risk (as measured by the Rapid Risk Assessment for Sexual Offense Recidivism) but
      not by psychopathy (as measured by the Psychopathy Checklist-Revised). Contrary
      to expectations, denial was associated with increased sexual recidivism among the
      low-risk offenders and with decreased recidivism among the high-risk offenders.
      Post hoc analyses suggested that the risk item most responsible for the
      interaction was "relationship to victims". For incest offenders, denial was
      associated with increased sexual recidivism, but denial was not associated with
      increased recidivism for offenders with unrelated victims. These interactions
      were substantially replicated in two independent samples (N = 490 and N = 73).
      The results suggest that denial merits further consideration for researchers as
      well as those involved in applied risk assessment of sexual offenders.

PMID- 17534715
TI  - Single-step centrifugal hematocrit determination on a 10-$ processing device.
AB  - We present a novel concept to process human blood on a spinning polymer disk for
      the determination of the hematocrit level by simple visual inspection. The
      microfluidic disk which is spun by a macroscopic drive unit features an upstream
      metering structure and a downstream blind channel where the centrifugally
      enforced sedimentation of the blood is performed. The bubble-free priming of the
      blind channel is governed by centrifugally assisted capillary filling along the
      sloped hydrophilic side-wall and the lid as well as the special shape of the dead
      end of the two-layer channel. The hematocrit is indicated at the sharp phase
      boundary between the plasma and the segregated cellular pellet on a disk
      imprinted calibrated scale. This way, we conduct the hematocrit determination of
      human blood within 5 min at a high degree of linearity (R(2) = 0.999) and at a
      high accuracy (CV = 4.7%) spanning over the physiological to pathological working
      range. As all processing steps including the priming, the metering to a defined
      volume as well as the centrifugation are executed automatically during rotation,
      the concept is successfully demonstrated in a conventional PC-CDROM drive while
      delivering the same performance (R(2) = 0.999, CV = 4.3%).

PMID- 17534716
TI  - Microvessel scaffold with circular microchannels by photoresist melting.
AB  - In this research, a new process that integrates the photoresist melting and soft
      lithography techniques to fabricate microvessel scaffolds with circular
      microchannels is proposed. The commercial software COMSOL Multiphysics (formerly
      known as FEMLAB) is the sought after procedure to optimize the structure of the
      microvessel scaffold. The photolithographic technique is applied to fabricate the
      negative photoresist THB-120N (JSR Inc.) based microstructure that is followed by
      melting to the final replica mold with its structure having convex semicircle
      cross-section. The replica mold is hence used to replicate PDMS to the top and
      bottom plates of a microvessel scaffold. These two half plates are bonded after
      having surface treatment by inductive coupled plasma (ICP) to form the complete
      scaffold with circular microchannels. Finally, the bovine endothelial cells (BEC)
      are cultured into the scaffold. Encouraging results by semi-dynamic seeding have
      been observed in this context, depicting the survival of the cells in the
      scaffold for up to 4 weeks.

PMID- 17534717
TI  - Pituitary tumor enlargement in two patients with acromegaly during pegvisomant
      therapy.
AB  - BACKGROUND: Several classes of pharmacological agents are approved for the
      medical therapy of acromegaly, including dopamine agonists, somatostatin analogs
      and a growth hormone receptor antagonist. Pegvisomant, a growth hormone receptor
      antagonist, suppresses IGF-1 levels into the normal range in over ninety percent
      of patients. However, increased tumor volume was reported in patients receiving
      pegvisomant who had not received prior radiotherapy. OBJECTIVES: To describe two
      patients with acromegaly who developed significant tumor enlargement on
      pegvisomant and discuss the potential mechanisms involved. INTERVENTION: Both
      patients received long-acting somatostatin analog (octreotide) therapy subsequent
      to incomplete transsphenoidal tumor resection. Octreotide did not normalize
      GH/IGF-1 levels in either patient but did control tumor mass size. Pegvisomant
      therapy was initiated after discontinuing octreotide. RESULTS: Both patients
      exhibited suppression of IGF-1 into the normal range during pegvisomant therapy.
      However, significant tumor enlargement occurred in both. Potential mechanisms for
      tumor enlargement include the natural tendency of the tumor to grow with time,
      discontinuation of tumor suppressive effects of the somatostatin analog, or a
      direct effect of pegvisomant. The presumed mechanism of tumor enlargement is by
      loss of the inhibitory effect on tumor growth when IGF-1 levels are reduced. This
      could also explain the increase in circulating GH levels in patients with
      acromegaly receiving pegvisomant; patient 1 demonstrated an 18-fold increase in
      circulating GH levels while receiving the drug. CONCLUSIONS: The mechanisms of
      tumor enlargement in patients with acromegaly on pegvisomant are likely
      multifactorial. Patients, especially those who have not received prior
      radiotherapy, should be closely monitored for tumor enlargement.

PMID- 17534718
TI  - Measuring clinically meaningful change following mental health treatment.
AB  - Assessment of clinically meaningful change is useful for treatment planning,
      monitoring progress, and evaluating treatment response. Outcome studies often
      assess statistically significant change, which may not be clinically meaningful.
      Study objectives are to: (1) evaluate responsiveness of the BASIS-24 using three
      methods for determining clinically meaningful change: reliable change index
      (RCI), effect size (ES), and standard error of measurement (SEM); and (2)
      determine which method provides an estimate of clinically meaningful change most
      concordant with other change measures. BASIS-24 assessments were obtained at two
      time points for 1,397 inpatients and 850 outpatients. The proportion showing
      clinically meaningful change using each method was compared to the proportion
      showing change in global mental health, retrospectively reported change, and
      clinician-assessed change. BASIS-24 demonstrated responsiveness at both aggregate
      and individual levels. Regarding clinically meaningful improvement and decline,
      SEM was most concordant with all three outcome measures; regarding no change, RCI
      was most concordant with all three measures.

PMID- 17534719
TI  - Developmental defects and seedling lethality in apyrase AtAPY1 and AtAPY2 double
      knockout mutants.
AB  - Previously it was shown that the Arabidopsis apyrase genes AtAPY1 and AtAPY2 are
      crucial for male fertility because mutant pollen (apy1-1; apy2-1) with T-DNA
      insertions in both genes could not germinate (Steinebrunner et al. (2003) Plant
      Physiol. 131: 1638-1647). In this study, pollen germination was restored and
      apyrase T-DNA double knockouts (DKO) apy1-1/apy1-1; apy2-1/apy2-1 were generated
      by complementation with AtAPY2 under the control of a pollen-specific promoter.
      The DKO phenotype displayed developmental defects including the lack of
      functional root and shoot meristems. In cotyledons, morphogenetic and patterning
      abnormalities were apparent, e.g., unlobed pavement cells and stomatal clusters.
      Another set of lines was created which carried either AtAPY1 or AtAPY2 under a
      dexamethasone-(DEX)-inducible promoter as an additional transgene to the pollen
      specific gene construct. Application of DEX did not reverse the DKO phenotype to
      wild-type, but some inducible lines exhibited less severe defects even in the
      absence of the inducer, probably due to some background expression. However, even
      these DKO mutants were seedling-lethal and shared other defects regarding cell
      division, cell expansion and stomatal patterning. Taken together, the defects in
      the DKO mutants demonstrate that AtAPY1 and AtAPY2 are essential for normal plant
      development.

PMID- 17534721
TI  - Contribution of quinone-reducing microorganisms to the anaerobic biodegradation
      of organic compounds under different redox conditions.
AB  - The capacity of two anaerobic consortia to oxidize different organic compounds,
      including acetate, propionate, lactate, phenol and p-cresol, in the presence of
      nitrate, sulfate and the humic model compound, anthraquinone-2,6-disulfonate
      (AQDS) as terminal electron acceptors, was evaluated. Denitrification showed the
      highest respiratory rates in both consortia studied and occurred exclusively
      during the first hours of incubation for most organic substrates degraded.
      Reduction of AQDS and sulfate generally started after complete denitrification,
      or even occurred at the same time during the biodegradation of p-cresol, in
      anaerobic sludge incubations; whereas methanogenesis did not significantly occur
      during the reduction of nitrate, sulfate, and AQDS. AQDS reduction was the
      preferred respiratory pathway over sulfate reduction and methanogenesis during
      the anaerobic oxidation of most organic substrates by the anaerobic sludge
      studied. In contrast, sulfate reduction out-competed AQDS reduction during
      incubations performed with anaerobic wetland sediment, which did not achieve any
      methanogenic activity. Propionate was a poor electron donor to achieve AQDS
      reduction; however, denitrifying and sulfate-reducing activities carried out by
      both consortia promoted the reduction of AQDS via acetate accumulated from
      propionate oxidation. Our results suggest that microbial reduction of humic
      substances (HS) may play an important role during the anaerobic oxidation of
      organic pollutants in anaerobic environments despite the presence of alternative
      electron acceptors, such as sulfate and nitrate. Methane inhibition, imposed by
      the inclusion of AQDS as terminal electron acceptor, suggests that microbial
      reduction of HS may also have important implications on the global climate
      preservation, considering the green-house effects of methane.

PMID- 17534720
TI  - New insights into Oryza genome evolution: high gene colinearity and differential
      retrotransposon amplification.
AB  - An approximately 247-kb genomic region from FF genome of wild rice Oryza
      brachyantha, possessing the smallest Oryza genome, was compared to the
      orthologous approximately 450-kb region from AA genome, O. sativa L. ssp.
      japonica. 37 of 38 genes in the orthologous regions are shared between japonica
      and O. brachyantha. Analyses of nucleotide substitution in coding regions suggest
      the two genomes diverged approximately 10 million years ago. Comparisons of
      transposable elements (TEs) reveal that the density of DNA TEs in O. brachyantha
      is comparable to O. sativa; however, the density of RNA TEs is dramatically
      lower. The genomic fraction of RNA TEs in japonica is two times greater than in
      O. brachyantha. Differences, particularly in RNA TEs, in this region and in BAC
      end sequences from five wild and two cultivated Oryza species explain major
      genome size differences between sativa and brachyantha. Gene expression analyses
      of three ObDREB1 genes in the sequenced region indicate orthologous genes retain
      similar expression patterns following cold stress. Our results demonstrate that
      size and number of RNA TEs play a major role in genomic differentiation and
      evolution in Oryza. Additionally, distantly related O. brachyantha shares
      colinearity with O. sativa, offering opportunities to use comparative genomics to
      explore the genetic diversity of wild species to improve cultivated rice.

PMID- 17534722
TI  - Biodegradation kinetics of select polycyclic aromatic hydrocarbon (PAH) mixtures
      by Sphingomonas paucimobilis EPA505.
AB  - Many contaminated sites commonly have complex mixtures of polycyclic aromatic
      hydrocarbons (PAHs) whose individual microbial biodegradation may be altered in
      mixtures. Biodegradation kinetics for fluorene, naphthalene, 1,5
      dimethylnaphthalene and 1-methylfluorene were evaluated in sole substrate, binary
      and ternary systems using Sphingomonas paucimobilis EPA505. The first order rate
      constants for fluorene, naphthalene, 1,5-dimethylnaphthalene, and 1
      methylfluorene were comparable; yet Monod parameters were significantly different
      for the tested PAHs. S. paucimobilis completely degraded all the components in
      binary and ternary mixtures; however, the initial degradation rates of individual
      components decreased in the presence of competitive PAHs. Results from the
      mixture experiments indicate competitive interactions, demonstrated
      mathematically. The generated model appropriately predicted the biodegradation
      kinetics in mixtures using parameter estimates from the sole substrate
      experiments, validating the hypothesis of a common rate-determining step.
      Biodegradation kinetics in mixtures were affected by the affinity coefficients of
      the co-occurring PAHs and mixture composition. Experiments with equal
      concentrations of substrates demonstrated the effect of concentration on
      competitive inhibition. Ternary experiments with naphthalene, 1,5
      dimethylnaphthalene and 1-methylfluorene revealed delayed degradation, where
      depletion of naphthalene and 1,5-dimethylnapthalene occurred rapidly only after
      the complete removal of 1-methylfluorene. The substrate interactions observed in
      mixtures require a multisubstrate model to account for simultaneous degradation
      of substrates. PAH contaminated sites are far more complex than even ternary
      mixtures; however these studies clearly demonstrate the effect that interactions
      can have on individual chemical kinetics. Consequently, predicting natural or
      enhanced degradation of PAHs cannot be based on single compound kinetics as this
      assumption would likely overestimate the rate of disappearance.

PMID- 17534723
TI  - Biodegradation of polyalcohol ethoxylate by a wastewater microbial consortium.
AB  - Polyalcohol ethoxylate (PAE), an anionic surfactant, is the primary component in
      most laundry and dish wash detergents and is therefore highly loaded in domestic
      wastewater. Its biodegradation results in the formation of several metabolites
      and the fate of these metabolites through wastewater treatment plants, graywater
      recycling processes, and in the environment must be clearly understood.
      Biodegradation pathways for PAE were investigated in this project with a
      municipal wastewater microbial consortium. A microtiter-based oxygen sensor
      system was utilized to determine the preferential use of potential biodegradation
      products. Results show that while polyethylene glycols (PEGs) were readily
      degraded by PAE acclimated microorganisms, most of the carboxylic acids tested
      were not degraded. Biodegradation of PEGs suggests that hydrophobe-hydrophile
      scission was the dominant pathway for PAE biodegradation in this wastewater
      community. Ethylene glycol (EG) and diethylene glycol (DEG) were not utilized by
      microbial populations capable of degrading higher molecular weight EGs. It is
      possible that EG and DEG may accumulate. The microtiter-based oxygen sensor
      system was successfully utilized to elucidate information on PAE biodegradation
      pathways and could be applied to study biodegradation pathways for other
      important contaminants.

PMID- 17534724
TI  - Physical characteristics of olive stone wooden residues: possible bulking
      material for composting process.
AB  - The present work focuses on the study of the physical characteristics of olive
      stone wooden residues at the prospect of its use as a bulking material in compost
      process. The physical characteristics that were studied according to particle
      mesh classification, were the apparent density, porosity, water holding capacity,
      air free space and air pressure drop. From the experimental results, it was
      proved that only the fraction of 6.8-12.5 mesh, which is 29.40% of the substrate,
      could maintain the moisture in the optimum range 40-60%. The fraction of the
      particles of 2.6-23.6 mesh, which was 74.68% of the substrate, had appropriate
      porosity for composting. It was also proved that for dried substrate and air
      velocity 300 m h(-1), acceptable pressure drop (10 cm H2O m(-1)) was observed for
      the fraction of the particles of 2.6-27.5 mesh, which was 80.08% of the
      substrate, while for dried substrate and air velocity 150 m h(-1), the respective
      fraction was particles of 2.6-37.9 mesh which accounted for the 89.48% of the
      substrate. Conclusively, olive oil processing solid residues have the physical
      characteristics, so as to be used for composting or as a substrate for co
      composting with high strength wastewater.

PMID- 17534725
TI  - Characterization of multiple novel aerobic polychlorinated biphenyl (PCB)
      utilizing bacterial strains indigenous to contaminated tropical African soils.
AB  - Contaminated sites in Lagos, Nigeria were screened for the presence of
      chlorobiphenyl-degrading bacteria. The technique of continual enrichment on
      Askarel fluid yielded bacterial isolates able to utilize dichlorobiphenyls
      (diCBs) as growth substrates and six were selected for further studies.
      Phenotypic typing and 16S rDNA analysis classified these organisms as species of
      Enterobacter, Ralstonia and Pseudomonas. All the strains readily utilized a broad
      spectrum of xenobiotics as sole sources of carbon and energy. Growth was observed
      on all monochlorobiphenyls (CBs), 2,2'-, 2,3-, 2,4'-, 3,3'- and 3,5-diCB as well
      as di- and trichlorobenzenes Growth was also sustainable on Askarel electrical
      transformer fluid and Aroclor 1221. Time-course studies using 100 ppm of 2-, 3-
      or 4-CB resulted in rapid exponential increases in cell numbers and CB
      transformation to respective chlorobenzoates (CBAs) within 70 h. Significant
      amounts of chloride were recovered in culture media of cells incubated with 2-CB
      and 3-CB, suggesting susceptibilities of both 2- and 3-chlorophenyl rings to
      attack, while the 4-CB was stoichiometrically transformed to 4-CBA. Extensive
      degradation of most of the congeners in Aroclor 1221 was observed when isolates
      were cultivated with the mixture as a sole carbon source. Aroclor 1221 was
      depleted by a minimum of 51% and maximum of 71%. Substantial amounts of chloride
      eliminated from the mixture ranged between 15 and 43%. These results suggest that
      some contaminated soils in the tropics may contain exotic micro-organisms whose
      abilities and potentials are previously unknown. An understanding of these novel
      strains therefore, may help answer questions about the microbial degradation of
      polychlorinated biphenyls (PCBs) in natural systems and enhance the potential use
      of bioremediation as an effective tool for cleanup of PCB-contaminated soils.

PMID- 17534726
TI  - Degradation of ethylbenzene by free and immobilized Pseudomonas fluorescens-CS2.
AB  - Pseudomonas fluorescens-CS2 metabolized ethylbenzene as the sole source of carbon
      and energy. The involvement of catechol as the hydroxylated intermediate during
      the biodegradation of ethylbenzene was established by TLC, HPLC and enzyme
      analysis. The specific activity of Catechol 2,3-dioxygenase in the cell free
      extracts of P. fluorescens-CS2 was determined to be 0.428 micromoles min(-1) mg(
      1) protein. An aqueous-organic, Two-Phase Batch Culture System (TPBCS) was
      developed to overcome inhibition due to higher substrate concentrations. In
      TPBCS, P. fluorescens-CS2 demonstrated ethylbenzene utilization up to 50 mM
      without substrate inhibition on inclusion of n-decanol as the second phase. The
      rate of ethylbenzene metabolism in TPBCS was found enhance by fivefold in
      comparison with single phase system. Alternatively the alginate, agar and
      polyacrylamide matrix immobilized P. fluorescens-CS2 cells efficiently degraded
      ethylebenzene with enhanced efficiency compared to free cell cultures in single
      and two-phase systems. The cells entrapped in ployacrylamide and alginate were
      found to be stable and degradation efficient for a period of 42 days where as
      agar-entrapped P. fluorescens was stable and efficient a period of 36 days. This
      demonstrates that alginate and polyacrylamide matrices are more promising as
      compared to agar for cell immobilization.

PMID- 17534727
TI  - The new incorporation bio-treatment technology of bromoamine acid and azo dyes
      wastewaters under high-salt conditions.
AB  - The accelerating effect of quinones has been studied in the bio-decolorization
      processes, but there are no literatures about the incorporation bio-treatment
      technology of the bromoamine acid (BA) wastewater and azo dyes wastewaters under
      high-salt conditions (NaCl, 15%, w/w). Here we described the BA wastewater as a
      redox mediator in the bio-decolorization of azo dye wastewaters. Decolorization
      of azo dyes was carried out experimentally using the salt-tolerant bacteria under
      the BA wastewater and high-salt conditions. The BA wastewater used as a redox
      mediator was able to increase the decolorization rate of wastewater containing
      azo dyes. The effects of various operating conditions such as dissolved oxygen,
      temperature, and pH on microbial decolorization were investigated experimentally.
      At the same time, BA was tested to assess the effects on the change of the
      Oxidation-Reduction Potential (ORP) values during the decolorization processes.
      The experiments explored a great improvement of the redox mediator application
      and the new bio-treatment concept.

PMID- 17534728
TI  - Seroprevalence of varicella antibodies among pregnant women in Lyon-France.
AB  - The purpose of the study was to calculate the seroprevalence of immunity to the
      varicella-zoster virus (VZV) infection and to evaluate the positive predictive
      value (PPV) and the negative predictive value (NPV) of the self-reported history
      of VZV infection in pregnant women. A cross sectional study was conducted in 18
      private medical analysis laboratories. Information on socio-demographic
      characteristics and past history of varicella or zoster were collected using a
      questionnaire. Blood samples were obtained to determine the serological levels of
      past exposure to VZV. Overall, 486 pregnant women were recruited. The
      seroprevalence of VZV antibodies was 98.8%. Six women were seronegative, of whom
      four were primiparous. The PPV was high (99.5%) while the NPV was only 10.3%. The
      PPV is a reliable marker of prior VZV infection. In contrast, a negative history
      does not predict lack of immunity and should be completed by serological analysis
      which might be introduced to routine antenatal blood tests.

PMID- 17534729
TI  - Mortality risks among heavy-smokers with special reference to women: a long-term
      follow-up of an urban population.
AB  - Increased mortality risks associated with smoking are well established among men.
      There are very few population-based studies comprising a sufficient number of
      heavily smoking women, measuring the direct effect of smoking on mortality risks.
      Between 1974 and 1992, 8,499 women and 13,888 men attended a health screening
      programme including reporting of smoking habits. Individuals were followed for
      total mortality until 2005. All-cause, cancer, cardiovascular, lung cancer and
      respiratory mortality were calculated in smoking categories <10 g per day, 10-19
      g per day, and > or =20 g per day with never-smokers as a reference group and
      with adjustments for co-morbidities, socio-economic and marital status. For
      respiratory mortality and lung cancer adjustments for FEV(1), socio-economic and
      marital status were performed. Smoking was associated with a two to almost
      threefold increased mortality risk among women and men. The relative risk (RR)
      with 95% confidence interval, (CI) for women who smoked 10-19 g per day was 2.44
      (2.07-2.87), and for those who smoked 20 g per day or more the RR (95% CI) was
      2.42 (2.00-2.92). Smoking was a strong risk factor for cardiovascular mortality
      among women, the RR (95% CI) for women who smoked 10-19 g per day was 4.52 (3.07
      6.64). Ex-smoking women showed increased risks of all-cause mortality; RR (95%
      CI) 1.26 (1.04-1.52) cancer (excluding lung cancer); RR (95% CI) 1.42 (1.07-1.88)
      and lung cancer RR (95% CI) 2.71 (1.02-7.23) mortality. However, the
      cardiovascular; RR (95% CI) 1.18 (0.69-2.00) and respiratory; RR (95% CI) 0.79
      (0.16-3.84) mortality risks were not statistically significant. This study
      confirms that as for men, middle-aged heavily smoking women have a two to
      threefold increased mortality risk. Adjustments for co-morbidity, socio-economic
      and marital status did not change these results.

PMID- 17534730
TI  - Factors affecting the distribution of a predatory mite on greenhouse sweet
      pepper.
AB  - The predatory mite Neoseiulus cucumeris is used for biological control of
      phytophagous mites and thrips on greenhouse cucumber and sweet pepper. In a
      previous study, N. cucumeris provided effective control of broad mite but was
      only rarely found on the sampled leaves, raising questions about the factors
      affecting N. cucumeris distribution. To determine the distribution of N.
      cucumeris, leaves of pepper plants were sampled three times per day: just after
      sunrise, at noon and just before sunset for two years and throughout a 24 h
      period in one year. The presence of other mites and insects was recorded. Biotic
      (pollen) and abiotic (temperature, humidity) factors were monitored from the
      three plant levels. The effect of direct and indirect sunlight on the mites was
      assessed. N. cucumeris was found primarily in flowers; however, the mite's
      distribution was affected by other predators (intraguild predation); in the
      presence of the predatory bug Orius laevigatus virtually no mites occurred in the
      flowers. Whereas temperature and humidity varied from the top to the lower level
      of the plants, apparently neither these factors nor the presence of pollen
      outside the flowers influenced mite distribution. N. cucumeris was found to be
      negatively phototropic; therefore N. cucumeris were pre-conditioned to light by
      rearing under light conditions for 4 months before being released. The light
      reared mites were initially more numerous during the noon sampling period,
      however, rearing conditions caused only a temporary and non-significant change in
      distribution.

PMID- 17534731
TI  - Nephropathology quiz page.

PMID- 17534732
TI  - Factors related to erythropoietin hypo-responsiveness in patients on chronic
      peritoneal dialysis.
AB  - BACKGROUND: The present study was aimed at investigating the factors related to
      hypo-responsiveness to erythropoietin in patients on chronic peritoneal dialysis
      (PD). METHODS: We studied 44 patients with end-stage renal disease who had been
      on PD for more than 6 months and on erythropoietin (EPO) >/=6,000 U/week for more
      than 3 months. We expressed EPO resistance index (ERI) as weekly EPO dose per
      hematocrit (Hct) per body weight. The dose of EPO was titrated to maintain a
      target Hct level between 33% and 36%. Patients were divided into two groups
      according to weekly EPO dose. We compared the various factors in those two groups
      and, by using correlation and linear regression analysis, investigated factors
      that might predict EPO resistance. RESULTS: There were 13 patients in the EPO
      <150 U/kg per week group and 31 patients in the EPO >/=150 U/kg per week group.
      Among those 31 patients, there were five patients on EPO >/=300 U/kg per week.
      Compared to the EPO <150 U/kg per week group, the EPO >/=150 U/kg per week group
      had a lower normalized protein catabolic rate (nPCR), lower level of serum
      albumin and higher C-reactive protein (CRP). Correlation analysis showed that the
      ERI had a statistically significant correlation with CRP (r = 0.303, P < 0.05),
      serum albumin (r = -0.26, P < 0.05), parathyroid hormone (PTH) (r = -0.307, P <
      0.05) and nPCR (r = -0.259, P < 0.05). These results show that CRP, serum
      albumin, PTH and nPCR are factors related to hypo-responsiveness. Multiple
      stepwise linear regression analysis showed that CRP was the most important
      independent predictor of EPO hypo-responsiveness. CONCLUSION: CRP, serum albumin,
      nPCR and PTH are factors related to hypo-responsiveness. Inflammation contributes
      significantly to EPO hypo-responsiveness.

PMID- 17534734
TI  - Calculation of coronary age using calcium scores in multiple ethnicities.
AB  - Coronary artery calcium (CAC) accumulation, a marker of atherosclerosis burden,
      differs significantly among patients of different ethnicities. It has been
      proposed that CAC scores can be used to assess the number of life years lost or
      gained by an individual with a given amount of coronary artery calcium.
      Therefore, we sought to develop a method to calculate the coronary age of an
      individual based on the extent of CAC in this subject compared to that of
      individuals of the same race, age and sex. We used median CAC scores from
      previously published data from the Multi-Ethnic Study of Atherosclerosis (MESA)
      to derive the predicted coronary age of subjects from 4 ethnic groups (White,
      Black, Hispanic and Chinese) of both sexes. With this method a 50-year-old white
      man with a CAC score of 40 has a coronary age of a 61-year-old white man; for a
      black man with a score of 40 the coronary age is 70. This method should allow
      patients to better understand the prognostic significance of their test results
      and may ensure a better compliance with preventive regimens.

PMID- 17534735
TI  - Two questionnaires for Parkinson's disease: are the PDQ-39 and PDQL equivalent?
AB  - BACKGROUND: Although there is a wide range of specific health-related quality of
      life (HRQoL) measures for Parkinson's disease (PD), their psychometric attributes
      have never been compared. OBJECTIVE: To compare the psychometric characteristics
      of the Parkinson's Disease Questionnaire-39 items (PDQ-39) and Parkinson's
      Disease Quality of Life Questionnaire (PDQL). METHODS: The PDQ-39 and PDQL were
      simultaneously applied to 187 PD patients. Additional assessments included Hoehn
      and Yahr staging, Schwab and England Scale (SES), Unified Parkinson's Disease
      Rating Scale, Pfeiffer's Short Portable Mental Status Questionnaire (SPMSQ) and
      Hospital Anxiety and Depression Scale (HADS). Criteria for acceptability, scaling
      assumptions, reliability, construct validity and precision were drawn up.
      RESULTS: Both the PDQ-39 and PDQL proved very similar in the following aspects:
      acceptability (no floor or ceiling effect); scaling assumptions (79.5% and 80%
      respectively of item-total correlations fitted the standard); internal
      consistency (PDQ-39 domains, alpha = 0.43-0.93; PDQL domains, alpha = 0.70-0.88);
      stability (intraclass correlation coefficient = 0.76-0.90); and internal validity
      (PDQ-39, r = 0.09-0.70; PDQL, r = 0.52-0.71). Convergent validity between the two
      questionnaires was moderate to high (r = -0.91 for summary indices). Precision
      was higher for the PDQ-39 Summary Index, and predictors were the same for both
      measures (mood disorders and disability). CONCLUSIONS: Although the psychometric
      properties tested are quite similar in both measures, mainly insofar as summary
      indices are concerned, differences in some attributes and structural content
      should nevertheless be considered when comparing both instruments.

PMID- 17534737
TI  - Psychometric properties of the Minnesota Living with Heart Failure--Brazilian
      version--in the elderly.
AB  - BACKGROUND: Heart failure (HF) has implications for the quality of life for any
      age range, more so for the elderly who simultaneously present other limitations
      imposed by multiple co-morbidities. Although there are several instruments to
      measure Health Related Quality of Life (HRQL), none is specific to the elderly
      with HF. Among disease-specific instruments, Minnesota Living with Heart
      Failure(LHFQ) has not been studied extensively among the elderly with respect to
      its psychometric properties. OBJECTIVE: The purpose of this study was to evaluate
      the convergent, divergent and discriminative validity of the Brazilian version of
      LHFQ applied to elderly HF patients. METHOD: One hundred and seventy (170)
      elderly were interviewed. LHFQ capacity to discriminate subjects among New York
      Heart Association (NYHA) Classes I, II and III/IV was analyzed. Convergent and
      divergent validity was evaluated through the correlation between the domains of
      LHFQ and the generic instrument, Medical Outcomes Study (MOS) 36-item Short-Form
      Health Survey (SF-36). RESULTS: The LHFQ total score and physical dimension sub
      scale discriminated between the three sub-groups of NYHA Classes I, II and III/IV
      (P < .0001). The emotional dimension discriminated NYHA Classes I and III/IV (P =
      .0034). The physical and emotional dimensions of the LHFQ and SF-36 were
      significantly correlated (coefficients from .46 to .70 for physical dimension and
      from .31 to .65 for emotional dimension). However, contrary to expectations, the
      divergent validity was not totally confirmed as there was no difference in the
      magnitude of the correlations between the LHFQ emotional and physical dimensions
      and the SF-36 role physical, social functioning and role emotional. Thus, the
      results suggest that LHFQ seems to be a valid tool to measure HRQL in the
      elderly, but new studies remain necessary to gain a better understanding of its
      discriminative validity for more advanced NYHA functional classes and for its
      divergent validity.

PMID- 17534738
TI  - Sharing experiences of user involvement in shaping new services: the story of a
      national patient group.
AB  - When the Cancer Genetics Pilots Programme was established in 2004, Macmillan
      Cancer Support undertook to create and facilitate the work of a "National User
      Reference Group". The purpose of this group was to give service user
      representatives (patients and carers) from each of the seven pilot projects
      regular opportunities to meet and share experiences and thus strengthen the
      influence of patients on the services. Macmillan commissioned a narrative writer
      to record key aspects of the national user group's work and influence. The
      emerging narrative accounts, created in collaboration with its members, provide a
      picture of a diverse group of skilled and enterprising individuals, enthusiastic
      about helping future patients. Service users have contributed to shaping
      projects, improving written information and sustaining the local services. In
      addition, project staff responsible for user involvement highlighted the value of
      training for user representatives and the need to remove financial and logistical
      barriers to participation. The national user group itself received vital support
      from Macmillan in the form of a dedicated "group facilitator", as well as
      continuous guidance and encouragement from a senior manager (an "organisational
      sponsor") present at all the group's meetings. By the end of 2006, the group
      discussions indicated that user involvement had developed to varying degrees and
      in different forms across the pilot projects. In the best case, patient
      representatives were being "treated as part of the team".

PMID- 17534739
TI  - Narrative-based medicine: when listening makes the difference.

PMID- 17534740
TI  - Delay pattern analysis of 368 patients with alcohol problems in one general
      practice.
AB  - OBJECTIVE: To describe the pattern of diagnosis of 368 patients with alcohol
      problems in one general practice in northwest England. METHODS: Records were
      searched retrospectively, and notes were made prospectively from 1996, of all
      patients who either admitted to drinking more than 50 units per week (men) or 35
      units per week (women), or with other mention of "alcohol problems". Any such
      record was considered to constitute an "alcohol problem". The interval between
      first presentation, using a standard problem list, and the date of identification
      of an alcohol problem was noted in both time and number of general practice
      consultations. RESULTS: 292 patients (79%) were diagnosed in the practice, 51
      (14%) in hospital, nine (2%) in a previous general practice, and 16 (4%)
      elsewhere. Thirty-nine per cent of patients were identified before the age of 35.
      Men were identified significantly quicker than women, and alcohol problems have
      been diagnosed significantly quicker since 1996. CONCLUSION: General practice was
      the major setting for the identification of alcohol problems in this population.
      Evidence from this series, probably the largest from a single practice, suggests
      patients were discovered more speedily in more recent years than earlier. This
      audit has educational value and could be used more widely in primary care to
      demonstrate how well we are diagnosing those whose problems come from their use
      of alcohol.

PMID- 17534741
TI  - The natural history of psychosomatic symptoms and their association with
      psychological symptoms: observations from the Population Study of Women in
      Gothenburg.
AB  - OBJECTIVE: To study the prevalence of subjective unspecified psychological
      symptoms (UPS) in a cohort of middle-aged women and the development of
      psychosomatic symptoms over 24 years. METHODS: In 1968-1969, 1462 randomly
      selected women, aged 38, 46, 50, 54 and 60, were recruited. A 24-year follow-up
      was performed in 1992-1993 (n=836). The same structured interview concerning
      psychological and psychosomatic symptoms was used on both occasions. RESULTS: The
      prevalence of UPS was 28% in 1968-1969 and 20% in 1992-1993. Women with UPS in
      1968-1969 were significantly more likely to have asthma/obstructive symptoms (34%
      vs 26%), headache (38% vs 22%) and abdominal symptoms (40% vs 21%), but not
      hypertension/high blood pressure (28% vs 28%), than women who did not report UPS.
      In 1992-1993, women with UPS in 1968-1969 were significantly still more likely to
      have asthmatic (25% vs 18%) and abdominal symptoms (44% vs 33%). Sixty-one per
      cent of women with UPS in 1968-1969 did not report such symptoms in 1992-1993,
      compared to 86% of women without UPS in 1968-1969 (p<0.001). CONCLUSION: Women
      reporting UPS seemed to have a higher frequency of simultaneous psychosomatic
      symptoms than women not reporting UPS. However, having UPS was apparently
      unassociated with the development of psychosomatic symptoms over time.
      Psychosomatic symptoms in women seem to be self-limiting and decrease with time.

PMID- 17534742
TI  - Once tired, always tired? Limitations in function over time of tired patients in
      Dutch general practice.
AB  - OBJECTIVE: To gain insight into limitations in function over time of general
      practice patients who presented and were diagnosed with "tiredness". METHODS: In
      a routine family-practice electronic register based on use of the International
      Classification of Primary Care (ICPC), 684 patients were identified who presented
      (in 1997 or 1998) with the complaint tiredness, who were given the same symptom
      diagnosis, and who still had this diagnosis on 1 August 1999. A questionnaire
      (WONCA/COOP charts, HAD Scale, recent medical care, tiredness and attribution)
      was sent to these 684 "cases" and 858 controls. In a logistic regression analysis
      (16 dichotomous variables), we constructed five models for optimizing sensitivity
      and specificity for the detection of patients with an episode of care for
      "tiredness". RESULTS: We received 385 fully completed questionnaires of cases, on
      average 19 (7~31) months after the start of their episode of care for
      "tiredness". The results of the 1997 and 1998 cases were similar. Cases did
      considerably worse than did the 385 optimally matched controls: e.g., seriously
      limited by tiredness: 52% of cases vs 32% of controls; poor overall health: 35%
      of cases vs 20% of controls; HAD Scale scores indicating anxiety or depression:
      about 20% of cases vs about 10% of controls. Highest sensitivity (70%) was
      reached by including poor overall health, recent medical care and HAD Scale
      depression score >10 in the model; and highest specificity (65%) by including
      poor overall health and a HAD Scale anxiety score >7. CONCLUSION: Patients who
      present with tiredness and receive the same diagnosis have a high probability of
      suffering from substantial limitations in function in the years following
      diagnosis. Their limitations are more serious than those of controls, but no
      indication is found for a specific limitation. The indicators are strongly
      related and concentrate around "poor overall health".

PMID- 17534743
TI  - How do receptionists view continuity of care and access in general practice?
AB  - BACKGROUND: Continuity of care is widely regarded as an important feature of
      general practice, but the role of receptionists in influencing continuity has
      been the subject of little research. OBJECTIVE: To explore how receptionists
      might influence access and continuity of care in general practice. METHODS: A
      questionnaire survey of receptionists in practices in Leeds, UK, was conducted.
      All 119 practices in Leeds were contacted to recruit receptionists via practice
      managers. A total of 148 receptionists responded from 50 practices. RESULTS: The
      majority of receptionists (140, 94%) perceived continuity as team continuity.
      Most (139, 93%) felt it was important for the patient to be seen on the same day
      by any doctor, rather than the usual doctor. They were less willing to ask
      patients for more details of a routine problem than an urgent one. The majority
      (113, 76%) thought that non-attendance was more related to patient issues than to
      their own behaviour. Organizational factors affected how receptionists offered
      appointments. Advanced access could impede longitudinal continuity and,
      indirectly, relational continuity. Having a policy to deal with urgent
      appointments or routine appointments could facilitate such continuity.
      CONCLUSION: The majority of receptionists perceived continuity as a team response
      rather than longitudinal. However, if relational continuity is to survive in UK
      and European general practice, educational and training measures would need to be
      taken to promote these values to receptionists.

PMID- 17534744
TI  - The complexity of patients' satisfaction with out-of-hours care: a qualitative
      study.
AB  - BACKGROUND: The national health service in the Republic of Ireland is one of a
      number of European health services currently undergoing significant reform. Out
      of-hours primary care has been at the forefront of this process of change, and
      although patients appear satisfied, the complexity of their response to changes
      in out-of-hours care has not been fully explored. OBJECTIVE: To conduct an
      analysis of qualitative data collected during a recent study of patients'
      satisfaction with out-of-hours care in order to explore the full range of
      patients' views and experiences. METHODS: All patients contacting a family-doctor
      out-of-hours cooperative over a designated 24-day period were forwarded a postal
      questionnaire. The questionnaire contained a section giving the patient the
      opportunity to add qualitative comments concerning their experience. The data
      were analysed according to the principles framework analysis using Nvivo
      software. RESULTS: Analysis of the data resulted in the development of the
      following thematic categories: service availability, service accessibility,
      efficiency, continuity of care and quality of care. There was a range of views,
      both positive and negative, apparent around these themes, with evidence of
      patients engaging in careful decisions and "trade-offs" in respect of their
      options for out-of-hours care. CONCLUSION: Patients hold a range of views that
      suggests the complexity around patient satisfaction with out-of-hours care. A
      qualitative methodological approach can compliment current approaches to the
      evaluation of patient satisfaction, facilitating the exploration of the full
      range of patients' views and experiences.

PMID- 17534745
TI  - Early intervention with inhaled corticosteroids in subjects with rapid decline in
      lung function and signs of bronchial hyperresponsiveness: results from the DIMCA
      programme.
AB  - BACKGROUND: Asthma is generally accepted as an inflammatory disease that needs
      steroid treatment. However, when to start with inhaled steroids remains unclear.
      A study was undertaken to determine when inhaled corticosteroids should be
      introduced as the first treatment step. OBJECTIVE: To investigate the
      effectiveness of early introduction of inhaled steroids on decline in lung
      function in steroid-naive subjects with a rapid decline in lung function in
      general practice. SUBJECTS: Patients with signs/symptoms suspect of asthma (i.e.,
      persistent and/or recurrent respiratory symptoms) and a decline in forced
      expiratory volume in 1 s (FEV(1)) during 1-year monitoring of 0.080 l or more and
      reversible obstruction (> or =10% predicted) or bronchial hyperresponsiveness
      (PC(20)< or =8 mg/ml) were studied. They had been identified in a population
      screening aiming to detect subjects at risk for chronic obstructive pulmonary
      disease (COPD) or asthma. DESIGN: A placebo-controlled, randomized, double-blind
      study. METHODS: 75 subjects out of a random population of 1155 were found
      eligible, and 45 were willingly to participate. Subjects were randomly treated
      with placebo or fluticasone propionate 250 microg b.i.d., and FEV(1) and PC(20)
      were monitored over a 2-year period. OUTCOME VARIABLES: The primary outcome
      measure was decline in FEV(1); the secondary outcome measure was bronchial
      hyperresponsiveness (PC(20)). RESULTS: 22 subjects were randomly allocated to the
      active group with inhaled corticosteroids and 23 to placebo. Change of FEV(1) in
      the active treated group was +43 ml in post-bronchodilator FEV(1) (p =0.341) and
      +62 ml/year (p =0.237) in pre-bronchodilator FEV(1) after 1 year, and -22 ml (p
      =0.304) for post-bronchodilator FEV(1) and -9.4 ml (p =0.691) for pre
      bronchodilator FEV(1) after 2 years, compared to placebo. The effect on PC(20)
      was almost one dose-step (p =0.627) after 1 year and one dose-step (p =0.989)
      after 2 years. CONCLUSION: In this study, the early introduction of inhaled
      corticosteroids in newly diagnosed asthmatic subjects with rapid decline in lung
      function did not prove to be either clinically relevant or statistically
      significant in reversing the decline in FEV(1). For PC(20), no significant
      changes were detected.

PMID- 17534746
TI  - Validation of the Italian version of the EUROPEP instrument for patient
      evaluation of general practice care.
AB  - OBJECTIVE: To describe the validity and reliability of the Italian version of the
      EUROPEP instrument for patient evaluation of general practice care. METHODS: A
      survey was performed among patients who visited a general practice (n=983), using
      the 23-item EUROPEP questionnaire. The scores are aggregated in two dimensions:
      "clinical behaviour" and "organization of care". The cultural adaptation of the
      questionnaire into Italian has been performed by using the formal translation
      procedures applied in other European countries. Data were analysed with respect
      to item response rate, item-scale correlation, internal consistency reliability
      and construct validity of the instrument. RESULTS: The item response rate was
      good for 17 items, acceptable for four items and problematic for one item. The
      item-scale correlation largely exceeded a value of 0.40 for all items in both
      scales. The internal consistency of the aggregated scores was also very good, the
      reliability coefficients being 0.95 for "clinical behaviour" and 0.90 for
      "organization of care". As expected, older age and better health status were
      associated with more positive evaluation of care. CONCLUSION: Our study confirms
      that, even in its Italian version, the EUROPEP is a valid and easy-to-use
      instrument for gathering information on patients' experience with and evaluation
      of general practice care.

PMID- 17534748
TI  - A new medical discipline in an old country: the history of family medicine in
      Turkey.

PMID- 17534747
TI  - Oral anticoagulation monitoring: a thorn in our side.

PMID- 17534757
TI  - [Imaging features in aortic syndromes].

PMID- 17534769
TI  - [Dicom-CDs--risks and adverse effects].

PMID- 17534770
TI  - [Clinical results with a detachable temporary vena cava filter].
AB  - PURPOSE: Evaluation of the feasibility of implantation and explantation and
      evaluation of the efficacy of a detachable and retrievable temporary vena cava
      filter. MATERIALS AND METHOD: The temporary vena cava filter "OptEase" (Cordis)
      is a nitinol filter derived from the "TrapEase" (Cordis) permanent filter, which
      is implantable transjugularly or transfemorally. In contrast to other temporary
      filters, this type can be detached and is not fixed on a catheter during
      implantation. Therefore, it is usable as a temporary as well as a permanent
      filter which can be retrieved up to 12 days after detachment with a special
      catheter using the loop technique. The "OptEase" filter was implanted in 11
      patients ranging in age from 19 to 82 (mean age 30 years). In 10 patients the
      filter was transfemorally implanted and explanted. In 1 patient implantation was
      performed transjugularly prior to surgery and explantation was performed
      transfemorally after surgery. All patients had a deep vein thrombosis or iliac
      vein thrombosis. In 3 patients the filter was implanted prior to surgery. In 2
      patients pulmonary embolism was identified. In 5 patients the filter was
      implanted prophylactically because of deep vein thrombosis according to
      interdisciplinary diagnosis. RESULTS: No pulmonary embolism occurred during
      implantation. All filters were able to be retrieved without complications using
      the loop technique on the 6th, 8th, 12th and 13th day. No captured thrombus
      material was in the filter. CONCLUSIONS: This new vena cava filter type is an
      easily implantable and retrievable system. Since this filter type is detachable
      without a need for venous access during implantation, there are no sterility
      problems. The filter can be left in the vena cava as a permanent system if
      explantation is not indicated.

PMID- 17534771
TI  - [CT-guided interventions in children].
AB  - In pediatric CT-guided interventions specific features have to be taken into
      account. Due to a lack of cooperation or limited ability to cooperate, procedures
      are often performed using analgosedation or general anesthesia. To provide
      radiation protection, justified indication for CT-guided intervention is
      necessary and sonography and MRI are to be preferred whenever possible. CT
      examinations also need to be dose-adapted with sequential scanning and a tube
      voltage and tube current reduction compared to pediatric diagnostic CT studies
      must be ensured. Gonad shields are recommended for male patients. Biopsy device
      selection depends on the assumed tumor entity since histology and also
      immunohistochemical, molecular pathological and cytogenetical analysis are
      necessary to differentiate pediatric tumors (small, round, blue cell tumors). In
      addition to diagnostic procedures, therapeutic interventions (drainage, injection
      therapies, neurolysis, and radiofrequency ablation) can also be used in children
      and can provide an alternative to surgery in selected cases. With justified
      indications and precise performance, CT-guided interventions can be successful in
      pediatric patients with limited risks.

PMID- 17534772
TI  - [Complaints in the follow-up of conservatively treated distal radius fractures-
      predictors in the initial radiograph].
AB  - PURPOSE: Radius fractures are frequent in adults, and the long-term results of
      conservative treatment remain disappointing. This study examines predictors for
      the clinical outcome in the initial radiograph. This will help to identify
      patients who will benefit from surgical treatment. MATERIALS AND METHODS: A
      cohort study including a standardized telephone interview (Cooney score) was used
      to identify all conservatively treated patients with a distal radius fracture
      over a five-year period. The additional selection criteria were: over 15 years
      old, initial X-ray available, patient reachable by phone for the follow-up
      interview. The following measurements were taken from the initial radiograph:
      radius-base angle, radial shortening, radiopalmar angle and intraarticular
      displacement. Correlations and a simple test to predict negative outcome were
      computed. RESULTS: Of the initially identified 2211 patients with distal radius
      fracture, 179 also fulfilled the other criteria. The patients were 56.2 years old
      on average (standard deviation SD = +/- 22.45 years) and 72 % were female. 60 %
      of the fractures were on the right side. The average follow-up was 4.3 years (SD
      +/- 1.66). The Cooney score results averaged 85 points (with 100 being the
      optimal and maximum score), indicating good or very good functional results in
      the long term follow-up for 61 % of patients. However, 31 % received a rating of
      fair or poor and therefore had an unfavorable outcome. With respect to the
      correlations, age and shortening of the radius (but not gender) had a significant
      influence on the functional result. Using an age of 75 years or above and a
      radial shortening of at least 4 mm to predict an unfavorable outcome, the
      sensitivity is only 16 %, but the positive predictive value is 73 % and the
      specificity is 96 %. CONCLUSION: In the analysis of the initial radiographs after
      distal radius fracture, age and radial shortening primarily correlate with
      functional results after four years after conservative treatment. Using the
      values age > or = 75 and radial shortening > or = 4 mm, it is possible to predict
      an unfavorable functional outcome with a positive predictive value of 73 %. This
      could aid in the indication of operative treatment.

PMID- 17534773
TI  - [Cephalic atresia].

PMID- 17534781
TI  - Are there limits to swimming world records?
AB  - The purpose of this article was to investigate whether swimming world records are
      beginning to plateau and whether the inequality between men and women's swimming
      performances is narrowing, similar to that observed in running world records. A
      flattened "S-shaped curve" logistic curve is fitted to 100-m, 200-m, and 400-m
      front-crawl world-record swimming speeds for men and women from 1 May 1957 to the
      present time, using the non-linear least-squares regression. The inequality
      between men and women's world records is also assessed using the ratio,
      Women's/Men's world record speeds. The results confirm that men and women's front
      crawl swimming world-record speeds are plateauing and the ratio between women's
      and men's world records has remained stable at approximately 0.9. In conclusion,
      the logistic curves provide evidence that swimming world-record speeds
      experienced a period of "accelerated" growth/improvements during the 1960 -
      1970s, but are now beginning to plateau. The period of acceleration corresponded
      with numerous advances in science and technology but also coincided with the
      anecdotal evidence for institutionalised doping. Also noteworthy, however, is the
      remarkably consistency in the women's/men's world record ratio, circa 0.9,
      similar to those observed in middle and long distance running performances. These
      finding supports the notion that a 10 % gender inequality exists for both
      swimming and running.

PMID- 17534782
TI  - An on-ice aerobic maximal multistage shuttle skate test for elite adolescent
      hockey players.
AB  - The aim of this study was to design an on-ice test to predict V.O (2max) in ice
      hockey players. 30 elite hockey players (age 14.7 +/- 1.5 years) participated in
      this study. The oxygen uptake was assessed at submaximal and maximal velocities
      during an on-ice intermittent maximal multistage shuttle skate test with a 1
      min/0.5-min work/rest ratio. The procedure consisted of skating back and forth on
      a distance of 45 m (stop and go) while following a pace fixed by an audible
      signal: initial velocity of 3.5 m . s (-1) with increments of 0.2 m . s (-1)
      every stage. The skating multistage aerobic test (SMAT) enabled the prediction of
      the V.O (2max) (ml . kg (-1) . min (-1)) from the maximal velocity (m . s (-1))
      by means of the following regression equation: V.O (2max) = 18.07 x (maximal
      velocity) - 35.596 (r = 0.97, SEE = 3.01). The test-retest correlation was 0.92
      and SEE = 0.56 stage (n = 23). Following the SMAT validation, an additional group
      of 112 elite male (age = 14.2 +/- 1.3 years) and 31 elite female (age = 14.0 +/-
      1.2 years) ice hockey players performed both the 20-m shuttle run test and the
      SMAT, which was more specific and accurate to predict V.O (2max). The overall
      results suggest that the SMAT is highly specific, valid and reliable for the
      prediction of V.O (2max) of ice hockey players.

PMID- 17534783
TI  - HRTP, prolonged ergometer exercise, and single sculling.
AB  - The use of the heart rate turn point (HRTP) to set target heart rate (THR) for
      prolonged rowing ergometer (E) and single scull rowing (R) was evaluated. Ten
      trained subjects (age 21.3 +/- 4.0 yrs; VO (2max) 4.77 +/- 0.62 l . min-1)
      performed incremental exercise tests and 30-min prolonged E and R. Expired air
      and heart rate (HR) were measured continuously. During E and R, blood lactate
      concentration (La) was measured at rest and after 5, 10, 20, and 30 min. HRTP and
      V (E)TP (2) were determined as the deflection point of the heart rate performance
      curve and the second TP in minute ventilation (V. (E)). No significant
      differences were found for work rate (W), HR, and VO (2) between HRTP and V.
      (E)TP (2) and they were significantly related (r = 0.94, p < 0.001; r = 0.96, p <
      0.001). Mean HR, VO (2), VCO (2), and V. (E) were not significantly different
      between E and R. La remained at a steady state in both E and R but was slightly
      higher in E. Tidal volume (V (T)) was found to be lower and breathing rate (BR)
      was significantly higher in R. HR at HRTP from an incremental rowing ergometer
      exercise test is valid to establish a THR consistent with constant metabolic
      training intensity in prolonged ergometer and single scull rowing.

PMID- 17534784
TI  - Effects of inspiratory muscle training on exercise capacity and spontaneous
      physical activity in elderly subjects: a randomized controlled pilot trial.
AB  - Inspiratory muscle training (IMT) has been shown to improve exercise capacity in
      diseased populations. We chose to examine the effects of eight weeks of IMT on
      exercise capacity and spontaneous physical activity in elderly individuals.
      Eighteen moderately active elderly subjects (68.1 +/- 6.8 years [mean +/- SD];
      range 58 - 78 years) were randomly assigned to either an experimental group (n =
      9) or a control group (n = 9) in a double-blind manner. All subjects underwent
      inspiratory muscle testing, treadmill exercise testing and a four-day measurement
      period of spontaneous physical activity (using accelerometry) both pre- and post
      intervention. The experimental group underwent eight weeks of incremental IMT
      using a pressure threshold device, while the control group underwent sham
      training using identical devices. After IMT training, inspiratory muscle strength
      (mean + 21.5 cm H (2)O; 95 % CI: 9.3, 33.7; p = 0.002), V.O (2peak) (+ 2.8 ml x
      min (-1) x kg (-1); 95 % CI: 0.5, 5.2; p = 0.022), time to exhaustion during a
      fixed workload treadmill test (+ 7.1 min; 95 % CI: 1.8, 2.4; p = 0.013) and time
      engaged in moderate-to-vigorous physical activity (+ 59 min; 95 % CI: 15, 78; p =
      0.008) improved. Except for a decline in moderate-to-vigorous physical activity,
      no significant changes were seen in the control group. Therefore, IMT may be a
      useful technique for positively influencing exercise capacity and physical
      activity in elderly individuals.

PMID- 17534785
TI  - Cardioprotective effect of spontaneous activity.
AB  - In the perspective of giving a better understanding of the cardioprotective
      effects attributable to the tandem low caloric intake and training, Lou/C rats
      would be an interesting model since these animals exhibit spontaneously these two
      characteristics for months, without any dietary manipulations or stressor
      stimuli. No information was so far available on their cardiac function.
      Therefore, the aim of this pilot study was (i) to document cardiac function
      before and after ischemia in this strain, and (ii) to investigate whether
      spontaneous wheel-running activity can improve the ability of cardiac muscle to
      recover its function after an ischemic period. Cardiac mechanical and metabolic
      functions were measured in isolated Langendorff hearts from Wistar sedentary,
      Lou/C sedentary, and Lou/C wheel-running male rats submitted to a 20-min low-flow
      ischemia and 20-min reperfusion. In Lou/C sedentary rats, rate-pressure product,
      an index of cardiac work, was decreased before ischemia as compared to Wistar
      sedentary animals (- 24 %, p < 0.05). After ischemia, cardiac mechanical function
      recovery did not significantly differ between these two groups. Nevertheless,
      flux of non-oxidative glycolysis was lower before and after ischemia in Lou/C
      sedentary animals than in Wistar sedentary rats. In Lou/C rats, during normoxic
      perfusion, wheel-running activity significantly decreased heart rate (- 15 %),
      oxygen consumption (- 2.2 %) and cardiac efficiency (- 37 %), whereas coronary
      flow and flux of non-oxidative glycolysis were significantly increased (+ 15 %
      and + 263 %, respectively). After ischemia, recovery of cardiac mechanical
      function and cardiac efficiency were improved in Lou/C wheel-running rats versus
      Lou/C sedentary animals (p < 0.05). In conclusion, the impact of ischemia
      reperfusion is similar between Lou/C- and Wistar sedentary rats. Spontaneous
      wheel-running activity decreases cardiac efficiency before ischemia and confers a
      protection against ischemia- and reperfusion-induced injury in isolated Lou/C rat
      hearts.

PMID- 17534786
TI  - Cold water recovery reduces anaerobic performance.
AB  - This study investigated the effects of cold water immersion on recovery from
      anaerobic cycling. Seventeen (13 male, 4 female) active subjects underwent a
      crossover, randomised design involving two testing sessions 2 - 6 d apart.
      Testing involved two 30-s maximal cycling efforts separated by a one-hour
      recovery period of 10-min cycling warm-down followed by either passive rest or 15
      min cold water immersion (13 - 14 degrees C) with passive rest. Peak power, total
      work and postexercise blood lactate were significantly reduced following cold
      water immersion compared to the first exercise test and the control condition.
      These variables did not differ significantly between the control tests. Peak
      exercise heart rate was significantly lower after cold water immersion compared
      to the control. Time to peak power, rating of perceived exertion, and blood pH
      were not affected by cold water immersion compared to the control. Core
      temperature rose significantly (0.3 degrees C) during ice bath immersion but a
      similar increase also occurred in the control condition. Therefore, cold water
      immersion caused a significant decrease in sprint cycling performance with one
      hour recovery between tests.

PMID- 17534787
TI  - Gluteus medius muscle atrophy is related to contralateral and ipsilateral hip
      joint osteoarthritis.
AB  - In order to understand the role of the GLUTEUS MEDIUS muscle (GM) in hip joint
      osteoarthritis, the objective of this study was to analyze the correlation
      between morphometric data of GM samples with osteoarthritis scores of ipsilateral
      and contralateral hips in 41 patients. GM samples obtained during unilateral hip
      replacement surgery were used to evaluate muscle fibers in the cross-sectional
      area (CSA) and other features indicative for muscle aging. Clinical symptoms were
      assessed by the Lequesne pain score. Hip osteoarthritis was graded by the
      Kellgren score and by measuring the sum joint space width (sumJSW) at three
      different articular locations and minimal JSW in a. p. radiographs. Varying
      degrees of GM muscle atrophy correlated with the pain score; pain score also
      correlated with radiographic signs of osteoarthritis. GM CSA was significantly
      correlated with all radiographic signs of the contralateral hip, but only with
      the sumJSW in the ipsilateral hip. It can be concluded that a weak GM may be the
      result of ipsilateral osteoarthitis, but may especially predispose the
      contralateral hip to develop osteoarthritis. This can be associated with an
      impaired GM capacity to avoid the shock impact in the load transfer during gait.
      Muscle strengthening is therefore recommended.

PMID- 17534788
TI  - Chemically standardized isolates from Cedrus deodara stem wood having anticancer
      activity.
AB  - An isolate "CD lignan mixture" comprising lignans from stem wood of Cedrus
      deodara consisted of (-)-wikstromal (75 - 79%), (-)-matairesinol (9 - 13%) and
      benzylbutyrolactol (7 - 11%) and was studied for its in vitro cytotoxicity
      against human cancer cell lines. The in vivo anticancer activity of CD lignan
      mixture was studied using Ehrlich ascites carcinoma and colon carcinoma (CA-51)
      models in mice. Its effect was also studied on annexin V binding, intracellular
      caspases and DNA fragmentation to gain insight into the mode of action. In vitro
      cytotoxicity studies showed significant dose-dependent effects against several
      cancer cell lines from different tissues such as breast, cervix, neuroblastoma,
      colon, liver, and prostate at 10, 30 and 100 microg/mL. The IC (50) values varied
      from 16.4 ng/mL to 116.03 microg/mL depending on the cell line. Comparative data
      of IC (50) values of CD lignan mixture showed a synergistic effect in comparison
      to the individual molecules, i. e., (-)-matairesinol, (-)-wikstromol present in
      CD lignan mixture . CD lignan mixture had the most pronounced effect on CNS cell
      lines followed by colon. The tumor regression observed with Ehrlich ascites
      carcinoma and CA-51 was 53% and approximately 54%, respectively, when CD lignan
      mixture was given at 300 mg/kg, I. P. for nine days in the Ehrlich ascites
      carcinoma model and 400 mg/kg, I. P. for the same period in the CA-51 model. It
      was comparable with 5-fluorouracil at 22 mg/kg and 20 mg/kg, respectively. CD
      lignan mixture at 10, 30 and 100 microg/mL increased the percentage of annexin V
      positive HL-60 cells to 1.9 - 17.18% as compared to control (1.04%). In K562
      cells CD lignan mixture at 10, 30 or 100 microg/mL and staurosporine (1 microM)
      showed 9.13%, 11.38%, 17.22% and 28.07% intracellular caspases activation,
      respectively. A distinct DNA laddering pattern was observed for treatment with
      the CD lignan mixture in HL-60, K562 (30 microg/mL and 100 microg/mL) and MOLT-4
      cells (30 microg/mL) after 24 h incubation. DNA cell cycle analysis indicated
      that CD lignan mixture at 10, 30 and 100 microg/mL increased the content of
      hypodiploid (sub G(1) phase) cells when compared to control (2.55, 5.4 and 6.25%
      vs. 0.27%). The present study indicates that CD lignan mixture has cytotoxic
      potential against human cancer cell lines. It has the ability to induce tumor
      regression in vivo. It induces apoptosis as indicated by annexin V positive
      cells, induction of intracellular caspases, DNA fragmentation and DNA cell cycle
      analysis.

PMID- 17534789
TI  - A Mycobacterium marinum zone of inhibition assay as a method for screening
      potential antimycobacterial compounds from marine extracts.
AB  - A novel screening method for antimycobacterial agents using Mycobacterium marinum
      was developed. M. marinum was selected as a model organism because it has a close
      phylogenetic relationship to M. tuberculosis, a relatively rapid doubling time,
      similar drug susceptibilities to M. tuberculosis, and less stringent safety
      requirements. More than 1000 crude marine and plant extracts were screened
      against M. marinum in a Zone of Inhibition (ZOI) assay, and twenty-one target
      extracts were identified. The crude organic extract of the marine sponge,
      Haliclona sp.10, was chosen for further investigation as it yielded a ZOI of 20
      mm at a concentration of 80 microg/disk. Following bioassay-guided fractionation,
      (-)-papuamine was isolated, and yielded a 15 mm ZOI at a concentration of 25
      microg/disk. In standard assays using M. marinum, (-)-papuamine exhibited both an
      MIC and an MBC95 of 6.25 microg/mL. This is the first report of antimycobacterial
      activity for (-)-papuamine. In addition, when (-)-papuamine and other natural
      product extracts were tested for activity against both M. marinum and M.
      tuberculosis, activity was comparable between the two species. These data
      indicate that (-)-papuamine is a promising lead for the development of new
      antimycobacterial agents and that M. marinum is a useful surrogate for the
      screening of antimycobacterial compounds.

PMID- 17534790
TI  - A patient centered decision making dialysis access algorithm.
AB  - Much controversy surrounds the establishment of proper planning, placement and
      management (the best practice pattern) of dialysis access. These include the
      dialysis type and modality selection, timing of access placement and who places
      the access. The lack of and the difficulty of performing randomized studies with
      multiple confounding factors, in an extremely heterogeneous and rapidly changing
      ESRD population demographics, only partly explains the dialysis access conundrum.
      Add to this the rapidly developing and competing technologies, the wide spectrum
      of the professional experience, bias and socio-economic forces to make the ESRD
      problems as multivariate and complex as life itself. This overview describes a
      dialysis access algorithm approach to the patient needing renal replacement
      therapy, considering long-term improved patient outcome as the ultimate
      objective.

PMID- 17534791
TI  - Intravascular catheters and biofilm control.
AB  - Intravascular catheters are the most common cause of nosocomially acquired
      bloodstream infections. Bacteria found adhering to the intraluminal surfaces of
      catheters are the principal source and cause of these infections. Adherent
      bacteria overtime are known to form multicellular communities which become
      encased within a three dimensional matrix of extracellular polymeric material
      known as biofilms, which are thought to be responsible for persistent infections.
      Consequently, a number of technologies have been developed to help prevent and
      control biofilms in intravascular catheters. One such approach involves
      impregnating catheter material with antimicrobial agents. Unfortunately these
      methods are not universally effective in preventing catheter-related biofilm
      infections. Technologies that utilise antimicrobials, as catheter locks have been
      shown to have more potential for preventing biofilm formation and reducing the
      incidences of catheter related bloodstream infections (CRBSI). This article
      discusses the significance of biofilms in intravascular catheters and determines
      whether the treatments available today are proving to be effective for
      controlling biofilms and draws attention to future avenues which are being
      investigated to control biofilms and therefore CRBSI.

PMID- 17534792
TI  - Color Doppler ultrasonography percutaneous transluminal angioplasty of vascular
      access grafts.
AB  - Percutaneous transluminal angioplasty (PTA) is a possible treatment for stenosis.
      This study aimed to verify the impact of a vascular access (VA) surveillance
      protocol, based on the detection of functional changes and their correction by a
      new PTA method for VA performed under color Doppler ultrasonography (CDU)
      guidance. We divided the patients into two groups: group A, before May 1999
      (retrospective study) without the surveillance protocol, and group B, from 1 May
      1999 to January 2001 (prospective study) with the surveillance protocol. Access
      blood flow (Qa) was assessed every 4 weeks by ultrasound velocity dilution. In
      cases of a reduction of >or=35% from the baseline value, VA was examined using
      CDU: if a stenosis >50% was detected, angioplasty was performed. In cases of Qa
      reduction <35% we continued monitoring. By Coxs multivariate analyses, only the
      use of PTA with or without stenting reduced the relative risk of thrombosis by
      64% during the follow-up (p=0.017 confidence intervals 88%-15%) in group B
      patients. Secondary patency was 80% for VA in which we performed PTA with or
      without stenting at 18 months, and 58% at 18 months in which we did not perform
      PTA. Our data show how PTA under CDU is useful to maintain and to improve graft
      patency. This PTA under CDU guidance allows patients to avoid surgical
      intervention, hospitalization, and adverse reactions to contrast media and
      exposure to ionizing radiation, with reduced cost and with better graft survival.

PMID- 17534793
TI  - Hemodialysis access without a shunt or catheter: the circulating port.
AB  - PURPOSE: To develop a new type of vascular access (VA) avoiding permanent
      arteriovenous (AV) shunting and intravenous catheter placement using a silicone
      plug inserted in the vessel wall. METHOD: Four different animal studies were
      conducted to verify the biologic safety of the concept, to check resistance to
      infection and accessibility and midterm patency. RESULTS: The circulating ports
      were found to be very easy to puncture, extremely resistant to infection and
      their midterm patency rate was acceptable. CONCLUSIONS: The circulating port
      seems to be a very promising hemodialysis (HD) access method, but it still has to
      be tested in clinical situations.

PMID- 17534794
TI  - Creation of secondary AV fistulas from failed hemodialysis grafts: the role of
      routine vein mapping.
AB  - Pre-existing forearm grafts lead to dilatation of upper arm veins of the
      ipsilateral arm that greatly facilitates the creation of secondary arteriovenous
      fistulas (AVF). In this retrospective review of 18 patients, the routine and
      periodical revision of failed grafts were discontinued. Vein mapping by physical
      examination or Duplex studies was performed prior to graft failure and a
      secondary AVF was created when the graft failed. Using this management strategy,
      an AVF creation success rate of 95% was achieved despite high incidence of co
      morbidity factors within the patient population. This success rate demonstrates
      the value of vein selection by vascular mapping prior to graft failure and early
      vascular access planning in the successful creation of secondary AVF.

PMID- 17534795
TI  - Early experiences of intraoperative ultrasound guided angioplasty of the arterial
      stenosis during upper limb arteriovenous fistula creation.
AB  - In recent years the high prevalence of diabetes and atherosclerosis in elderly
      uremic patients starting hemodialysis (HD) has led to the increase in the risk of
      vascular access (VA) failure caused by pre-existing arterial diseases, including
      both VA slow maturation and early failure, and upper limb ischemic symptoms.
      Recently, in performing radial (R), brachial (B) and ulnar (U) artery (A)
      percutaneous transluminal angioplasty (PTA) in HD patients affected by access
      thrombosis, with insufficient blood flow and severe upper limb ischemia, good
      outcomes have been reported. Nevertheless, these procedures were performed after
      arteriovenous fistula (AVF) creation. About 2 years ago, we approached an intra
      operative ultrasound-guided transluminal angioplasty (IUTA) performed during AVF
      creation, using the arterial incision, necessary because of the anastomosis, to
      introduce the necessary devices for the IUTA. The arterial stenosis having
      undergone IUTA was diagnosed by a preliminary ultrasound examination. Ultrasound
      guidance during the procedure is necessary for correct balloon location in the
      stenosis site. We treated seven patients (four diabetics), mean age 76 + 5 yrs.
      In all cases, the radial arteries because of hyposphygmia, were unfit for AVF
      creation. Four distal radio-cephalic AVFs at the wrist were created in patients
      1, 3, 4 and 5; in the other three patients (2, 6 and 7), with failure or
      thrombosis of previous distal AVFs, an immediately upstream anastomosis was
      performed. In all cases, first, the area selected to perform the AV anastomosis
      was exposed, then the AR was incised, and the introductory metallic guide wire
      and the angioplasty catheter (with dimensions decided after PUS), were
      introduced. The balloon was inflated to 8-13 atm for 30-35 sec. In two patients a
      stent was also positioned. Later, a side-to-side AVF was created, closing the
      distal venous vessel. Patient follow-up ranged from 6-22 months. The ultrasound
      evaluation after IUTA showed the correction of all the stenosis treated. AVF
      maturation was good, except for the stented ones, which were inadequate. In
      conclusion, our early experience shows IUTA could be an adequate and effective
      procedure allowing the use of the stenotic arteries (otherwise unsuitable) for
      AVF creation. In our experience, stenting after IUTA does not add any other
      advantages.

PMID- 17534796
TI  - Risk of vascular access thrombosis in patients with systemic lupus erythematosus
      on hemodialysis.
AB  - INTRODUCTION: Anticardiolipin antibody is associated with increased risk of
      vascular access thrombosis (VAT) in hemodialysis (HD) patients. Systemic lupus
      erythematous (SLE) patients have a high prevalence of anticardiolipin antibodies,
      but it is not clear whether these patients are at high risk of developing
      vascular access thrombosis. METHODS: Thirty six SLE patients on HD, who had
      either an arterio-venous (AV) graft or AV fistula as vascular access, and were
      not on anticoagulation treatment, were retrospectively identified at Henry Ford
      Hospital. A similar number of patients without SLE, matched for age, sex, race
      and type of vascular access were selected as a control population. Vascular
      access thrombosis rate at one year was compared between two groups. RESULTS: Mean
      age at dialysis was 36+/-10 years in 36 SLE patients (28 females, 8 males) and
      was 38+/-6.4 years in 36 non-SLE patients (29 females, 7 males). Of all patients,
      29/36 (80.5%) SLE and 27/36 (75%) non-SLE patients had AV grafts, whereas the
      rest had AV fistulas as vascular access (19.5% SLE and 25% non-SLE patients). Out
      of 36 SLE patients, 24 (66.6%) patients developed VAT at one year as compared to
      14 (38.9%) patients in non-SLE group (p<0.05). The odds ratio of VAT in SLE
      patients was 3.1 (95% CI 1.2-8.2). CONCLUSION: SLE patients on hemodialysis are
      more likely to develop vascular access thrombosis as compared to non-SLE
      patients.

PMID- 17534797
TI  - Serum LDL levels are a major prognostic factor for arteriovenous fistula
      thrombosis (AVFT) in hemodialysis patients.
AB  - INTRODUCTION: Arteriovenous fistula thrombosis (AVFT) is still a common cause of
      morbidity in patients undergoing regular hemodialysis (HD). Many factors have
      been found to induce AVFT. Some of those factors are local and others are
      systemic ones. In this study, we evaluated some local and systemic factors
      simultaneously, to predict the most potent risk factor for AVFT in HD patients.
      PATIENTS AND METHODS: One hundred and eighteen patients aged 20-80 yrs with end
      stage renal disease (ESRD) were evaluated prospectively for a period of 14
      months. First, anticardiolipin antibodies (ACLA), TG, cholesterol, low density
      lipoprotein (LDL) and high density lipoprotein (HDL) were analyzed by
      conventional methods. Other basic data were accessed from patients medical
      records. All fistulas were evaluated clinically as patent at the start of this
      study. Patients were followed-up for any evidence of AVFT within 14 months.
      Finally, all factors (diabetes, hypertension, presence of ACLA, ultrafiltration
      >or=3 L, age, gender, weight, hypotension during dialysis, fistula site, epoetin
      alpha usage, TG, HDL, LDL and total cholesterol) were analyzed in a stepwise
      regression analysis. RESULTS: Eighteen episodes of AVFT documented with Doppler
      sonography occurred in 17 patients (15.3%). Regression analysis showed only LDL
      values were the AVFT predictor in our patients (p=0.002, beta-coefficient=0.3).
      Kaplan-Meier analysis showed a significantly lower AVF patency time in patients
      with LDL >130 mg/dl than those with LDL <130 mg/dl (log rank=0.0014). DISCUSSION:
      LDL value is a major prognostic factor for AVFT in HD patients and lowering it to
      <130 mg/dl could improve fistula patency.

PMID- 17534798
TI  - Jugular vein-mammary artery fistula after catheterism for hemodialysis: case
      report.
AB  - The demographic characteristics of hemodialysis (HD) patients increase the need
      for the tunneled cuffed permanent catheter (TCC) as a definitive vascular access
      (VA) for HD. The internal jugular vein is increasingly being used as a route for
      TCC or temporary catheter placement and can be associated with serious
      complications. Among them other authors have described arteriovenous fistula
      (AVF) creation between the common carotid artery and the right jugular vein. We
      describe a case of an AVF between the right internal jugular vein and the right
      internal mammary artery. The fistula was detected during the TCC placement in a
      patient who underwent several jugular and subclavian catheterisms for HD in her
      clinical history.

PMID- 17534799
TI  - Massaging thrombosed PTFE hemodialysis access graft - recipe for disaster.
AB  - Early thrombosis of a polytetrafluoroethylene (PTFE) graft used for hemodialysis
      vascular access can result from technical error or hypotension and hypovolaemia
      in the immediate postoperative period. Massaging a graft to dislodge a freshly
      formed thrombus with a view to restoring blood flow can lead to acute limb
      ischaemia from embolisation of the artery as a result of migration of the
      thrombus from the arterial end of the graft, hence massaging of thrombosed grafts
      should be avoided. This report describes the management of a 35-year-old diabetic
      male who developed acute ischaemia of hand due to embolisation of the radial
      artery following massage of a thrombosed brachio-basilic forearm PTFE loop graft.

PMID- 17534800
TI  - Salvage of arteriovenous fistula by angioplasty of collateral veins establishing
      a new channel.
AB  - Patents with end-stage renal disease depend on the patency of their dialysis
      access. As these patients have only finite access options, and no access lasts
      indefinitely, it is imperative that each access should be maintained for as long
      as possible. This report describes a case of salvage of an upper arm fistula by
      repeated angioplasty of the collateral veins after the main out flow vein was
      occluded and could not be recanalyzed.

PMID- 17534801
TI  - Percutaneous, non-surgical placement of tunneled, cuffed, external jugular
      hemodialysis catheters: a case report.
AB  - The right internal jugular vein is widely accepted as the vessel of choice for
      placement of long-term central venous catheters for hemodialysis. As vascular
      access sites become progressively depleted, alternate anatomic locations for
      access must be sought. We describe a non-surgical (fluoroscopy assisted,
      percutaneous) technique for placement of external jugular, tunneled, cuffed
      hemodialysis catheters, and provide long-term blood flow and dialysis adequacy
      data for EJV catheters.

PMID- 17534802
TI  - Displacement of the inferior vena cava as a factor limiting catheter performance
      in long-term hemodialysis patients.
AB  - We report a case of a lady affected by autosomal dominant polycystic kidney
      disease who had been on hemodialyis for 24 years. She has exhausted all options
      for arterious-venous fistula. The presence of an acquired anatomical abnormality
      was an obstacle in order to get appropriate blood flow from standard tunnelled
      femoral catheters. The enlarged right kidney was pushing the inferior vena cava
      to the left side of the abdomen, and the abnormality was demonstrated by
      phlebography. Only after placing a cuffed catheter 53 cm long in her left femoral
      vein we could dialyze efficiently. Venography is mandatory before placing a
      cuffed catheter especially in uremic patients with long history of access
      failure, because it saves costs.

PMID- 17534804
TI  - Surgical anatomy of the deep lateral orbital wall.
AB  - PURPOSE: To determine the exact anatomic location and volume of the thickest
      section of the greater wing of the sphenoid bone (trigone), which is removed
      during deep lateral orbital wall decompression. METHODS: Eighteen dried skulls
      were used to determine the exact anatomic location and computed tomography (CT)
      images of 20 patients (10 male, 10 female) were used for volumetric calculations.
      RESULTS: Mean values were 14.5 mm for the orbital rim to inferior orbital fissure
      distance, 23.3 mm for rim to trigone distance, 13.0 mm for width of the trigone
      base, 5.8 mm for trigone to orbital apex distance, and 12.3 mm for trigone
      height. The width of the narrowest section of the trigone was 5.2 mm. The trigone
      was found to have a lower segment (0.92 cc) neighboring the inferior orbital
      fissure, and an upper segment (0.32 cc) adjoining the thick substance of frontal
      bone. The narrowest part between these two segments was located just at the
      superior border of the lateral rectus muscle. CONCLUSIONS: The authors recommend
      avoiding the thin rectangular portion located in the inter-fissural area adjacent
      to the superior orbital fissure. A high intersubject variability underscores the
      need for individualized preoperative analysis by imaging studies.

PMID- 17534805
TI  - Eyeball muscles' diameters versus volume estimated by numerical image
      segmentation.
AB  - PURPOSE: To determine the clinical usefulness of the numerical segmentation image
      technique (NSI) in estimating the volume of extraocular muscles and to compare
      this value to widely used measurements of single diameters of the muscles.
      METHODS: Forty-five patients underwent magnetic resonance examinations in 1.5-T
      scanner. SE T1 sequences in transversal and coronal planes were provided and data
      were sent to a personal computer, where the degree of exophthalmos, horizontal
      diameter of medial rectus muscles, and vertical diameter of inferior rectus
      muscles were determined on the basis of two-dimensional images. The quantity
      estimation of all eye muscles volumes using NSI application in three-dimensional
      space was carried out with use of level set segmentation algorithm. RESULTS: A
      strong correlation between the total eye muscle volume and degree of exophthalmos
      was determined. The usefulness of measuring single diameters for estimating the
      muscles' enlargement was confirmed. The difference between a single muscle's
      volume and its width also was confirmed. Estimates of muscle volume correlate
      with the degree of exophthalmos more accurately than measurements of single
      diameters. CONCLUSIONS: The NSI technique is a clinically useful application,
      providing objective data calculated individually for each orbit. It allows an
      objective estimation of the pathologic processes leading to exophthalmos and may
      be especially helpful in monitoring discrete changes in the muscles volume during
      treatment.

PMID- 17534806
TI  - Optimal dosage of cyclopentolate 1% for complete cycloplegia: a randomized
      clinical trial.
AB  - PURPOSE: To determine the optimal dosage of cyclopentolate for adequate
      cycloplegia with minimal side effects. METHODS: A prospective randomized clinical
      trial of patients 3.5 to 20 years of age referred to a strabismus clinic during a
      1-year period. Eligible patients were randomly divided into three groups. In
      Group 1, the cycloplegic effect of one drop of cyclopentolate was compared with
      two drops; in Group 2, the effect of two drops was compared with three drops; and
      in Group 3, the effect of one drop was compared with three drops. RESULTS: This
      study includes 192 eyes of 96 patients with a mean age of 11.0 +/- 5.7 years.
      Strabismus was present in 43 patients (44.8%). A total of 146 patients (76%) were
      hyperopic, 33 (17.2%) were myopic, and 13 (6.8%) were slightly hyperopic or
      myopic at the two stages of the study. Overall, only 16 eyes, including 9 eyes in
      Group 1 (16.4%), 2 eyes in Group 2 (3.2%), and 5 eyes in Group 3 (8.6%), had > or
      = 0.5 D difference in spherical equivalent refractive error at two stages of the
      study; however, intergroup differences were not statistically significant
      (p=0.16, chi-square test). Within each group, the percentage of eyes with <0.5 D
      difference was significantly greater than those with > or = 0.5 D difference
      (p<0.001 in all three groups, binomial test). Side effects were more prevalent
      using more frequent drops. CONCLUSIONS: A single drop of cyclopentolate 1%
      suffices for cycloplegic refraction. There were less frequent side effects using
      one drop of cyclopentolate, compared to two or three drops.

PMID- 17534807
TI  - Factors affecting changes in astigmatism before and after suture removal
      following penetrating keratoplasty.
AB  - PURPOSE: To analyze the factors related to changes in astigmatism before and
      after suture removal in patients who underwent penetrating keratoplasty (PK).
      METHODS: The study group consisted of 171 consecutive PKs in 171 patients.
      Keratometric astigmatism was measured before and after suture removal in all
      patients. The vectorial difference for each eye was calculated between the
      examination before suture removal and the first year after suture removal. The
      vectorial difference values were compared with the possible factors affecting
      astigmatic change such as age of the patient, donor-recipient trephine diameter
      difference, preoperative diagnosis, and time of suture removal. All sutures were
      removed completely in one session. The vectorial difference values of all groups
      were compared with each other statistically. RESULTS: Before suture removal, the
      mean cylinder was 4.40 +/- 3.24 D; it was 3.96 +/- 2.19 D at 1 year after suture
      removal. The net difference of astigmatism was -0.27 +/- 3.50. The mean value of
      vectorial difference for all patients was 4.93 +/- 4.02 D. There was a
      statistically significant negative correlation between the trephine diameter
      difference and the vectorial difference (r= -0.582, p<0.01). There was a
      significant change in vectorial difference values in patients with high pre
      suture removal astigmatism. Patients with keratoconus had a positive correlation
      between the pre-suture removal astigmatism and the vectorial difference (r=0.615,
      p=0.038). CONCLUSIONS: After suture removal following PK, unexpected high levels
      of astigmatic change could be encountered due to donor-recipient trephine
      diameter difference and underlying primary diagnosis such as keratoconus. In
      particular, high level astigmatism before suture removal has a greater risk of
      increased astigmatic change after suture removal.

PMID- 17534808
TI  - ThinOptX vs AcrySof: comparison of visual and refractive results, contrast
      sensitivity, and the incidence of posterior capsule opacification.
AB  - PURPOSE: To evaluate the visual and refractive results, the changes in contrast
      sensitivity, and the incidence of posterior capsule opacification (PCO) after the
      implantation of UltraChoice 1.0 ThinOp-tX (ThinOptX Inc.) intraocular lens (IOL)
      and conventional acrylic foldable IOL (AcrySof MA30AC). METHODS: Twenty-five
      patients were randomized into two groups prospectively. In Group 1,
      microincisional phacoemulsification and the ThinOptX IOL implantation were
      applied in one eye, and in Group 2, conventional phacoemulsification and the
      AcrySof IOL implantation were applied in the fellow eye. Uncorrected visual
      acuity (UCVA) and best-corrected visual acuity (BCVA), surgically induced
      astigmatism (SIA), contrast sensitivity, and the incidence of PCO were observed
      in the two groups and comparisons were made. RESULTS: Mean follow-up period was
      12.8+/-1.5 months (range 11 to 14 months). In the last follow-up examination,
      UCVA and BCVA were significantly lower and the PCO scores were significantly
      higher in Group 1 (p<0.05). Although SIA was lower in Group 1, the difference was
      not statistically significant. Contrast sensitivity in higher spatial frequencies
      was significantly lower in Group 1 in the 6th month and 12th month visits.
      Capsular contraction was seen in 3 eyes (12%) in Group 1 whereas there was no
      capsular contraction or phimosis in Group 2. CONCLUSIONS: Long-term evaluation of
      the ThinOptX IOL concludes with an increased rate of PCO, a diminished resistance
      to the capsular contraction vs the AcrySof IOL, and a decrease in visual
      performance. The poor after cataract performance of this rollable lens shows that
      microphacoemulsification and ThinOptX IOL implantation is not as effective as
      conventional hacoemulsification and AcrySof IOL implantation in the long term.

PMID- 17534809
TI  - Comparison of divide and conquer and phaco-chop techniques during fluid-based
      phaco-emulsification.
AB  - PURPOSE: To determine whether, similar to ultrasound phaco-emulsification,
      applied energy and surgery time decrease using phaco-chop nucleus fragmentation
      method compared to divide and conquer technique using the fluid-based system.
      METHODS: This prospective, comparative, randomized clinical study included
      patients with cataract who were randomly assigned to use either standard divide
      and conquer technique (25 eyes of 25 patients, Group 1) or Nagahara phaco-chop
      maneuver (25 eyes of 25 patients, Group 2) during fluid-based phaco
      emulsification. Surgical parameters were recorded and patients were examined 1
      day, 10 days, and 1 month after surgery. Statistical analyses were performed
      using the paired test of Wilcoxon. RESULTS: Fluid-based time, mean fluid-based
      magnitude, effective fluid-based time, and the number of pulses were
      significantly less using phaco-chop technique compared to divide and conquer
      method (p<0.001). Surgery time was similar using the two nucleofractis techniques
      (p=0.97). Visual acuities showed no statistical differences between the two
      groups (p>0.05). CONCLUSIONS: Nuclear fragmentation can be performed with
      Nagahara phaco-chop technique using the fluid-based system as well. The applied
      fluid-based energy decreases compared to divide and conquer method. However,
      surgery time is not reduced due to the difficulties reaching the full occlusion
      necessary to hold the nucleus during the chop maneuver.

PMID- 17534810
TI  - A comparison of higher order aberrations in eyes implanted with AcrySof IQ SN60WF
      and AcrySof SN60AT intraocular lenses.
AB  - PURPOSE: To evaluate the efficacy of AcrySof SN60WF aspheric intraocular lens
      (IOL) in decreasing spherical aberration and total higher order aberrations
      (HOAs) after cataract surgery compared to the spherical SN60AT lens. METHODS:
      Wavefront analysis was conducted on 28 eyes of 28 patients that underwent un
      complicated phacoemulsification with implantation of either SN60WF (15 eyes) or
      SN60AT lenses (13 eyes). Eyes with a history of uveitis, retinal diseases, and
      previous surgery were excluded. RESULTS: SN60WF eyes had less mean absolute
      spherical aberration than SN60AT eyes both at 4 mm (0.04+/-0.03 vs 0.11+/-0.03
      RMS, p<0.0001) and 6 mm pupils (0.09+/-0.04 vs 0.43+/-0.12 RMS, p<0.0001). Mean
      total HOAs was lower in the SN60WF group at 6 mm pupils (0.44+/-0.14 vs 0.56+/
      0.13 RMS, p=0.0274), while no difference was seen at 4 mm pupils (0.20+/-0.10 vs
      0.25+/-0.08 RMS, p=0.160). There were no clinically significant differences
      between the SN60WF and SN60AT IOLs both at 4 and 6 mm pupils in terms of coma
      (0.16+/-0.07 vs 0.18+/-0.09 RMS, p=0.514 and 0.25+/-0.12 vs 0.23+/-0.12 RMS,
      p=0.664) and trefoil (0.14+/-0.09 vs 0.10+/-0.05 RMS, p=0.167 and 0.28+/-0.12 vs
      0.23+/-0.07 RMS, p=0.199). There were no differences be-tween groups in mean age,
      axial length, postoperative spherical equivalent, IOL power, or corneal
      curvature. CONCLUSIONS: An aspheric posterior optic IOL design with thinner
      center effectively reduces the positive ocular spherical aberration observed in
      the pseudophakic and elderly eyes, especially at larger pupillary diameters (6
      mm), with no notable increase in coma. However, reduction in total ocular HOAs
      was only significant at 6 mm pupils.

PMID- 17534811
TI  - Comparison of anterior chamber depth measurements using Orbscan II and IOLMaster.
AB  - PURPOSE: To evaluate and compare anterior chamber depth (ACD) measurements using
      Orbscan II (Bausch & Lomb, Rochester, NY) and IOLMaster (Carl Zeiss Meditec AG,
      Jena, Germany). METHODS: In this prospective clinical study, the authors measured
      ACD of 145 phakic eyes of 30 healthy volunteers and 115 patients using Orbscan II
      and IOLMaster. Average patient age was 52.9+/-19.4 (range 16 to 87) years. ACD
      was evaluated from corneal epithelium to anterior lens surface. Additionally,
      axial length (AL) was measured using the Zeiss IOLMaster to calculate the
      regression coefficient between AL and ACD. RESULTS: Mean ACD was 3.35+/-0.43 mm
      (range 2.01 mm to 4.37 mm) using Orbscan II and 3.36+/-0.41 mm (range 2.09 mm to
      4.24 mm) using IOLMaster. Mean total axial length was 24.04 mm +/- 2.1 mm (range
      20.7 mm to 31.41 mm). The linear regression coefficient of ACD between both
      methods was R=0.95. ACD and AL correlated only slightly (R=0.57). The Spearman
      coefficients of rank correlation were 0.94 and 0.61, respectively. A p value less
      than 0.01 (paired Wilcoxon test) was considered statistically significant.
      However, a significant difference was not calculated comparing ACD measurements
      using both systems and the Bland-Altman-Plot showed 95% of the differences
      ranging between 0.25 and -0.27 mm. CONCLUSIONS: Regarding clinical application,
      both systems seem to be equally good and interchangeable in clinical practice in
      terms of ACD evaluation.

PMID- 17534812
TI  - Is intracameral lidocaine really effective in cataract surgery?
AB  - PURPOSE: To evaluate the usefulness of intracameral lidocaine in cataract surgery
      under topical anesthesia and especially if the patient wanted intravenous
      sedation preoperatively. METHODS: In this prospective study 96 patients were
      randomly assigned to receive 0.5 cc of balanced salt solution (Group 1) or 1%
      unpreserved lidocaine (Group 2). Patients who wanted sedation received
      intravenous midazolam hydrochloride. All surgery was done by one surgeon using a
      clear corneal technique. RESULTS: Mean pain scores were 0.73 (of a maximum 3) in
      Group 1 and 0.54 in Group 2; the difference between groups was not statistically
      significant. Forty patients in Group 1 (83%) and 44 patients in Group 2 (92%)
      reported no discomfort or only mild discomfort. The two study groups were
      comparable in need for intravenous midazolam. Logistic regression analysis showed
      a significant relationship between pain scores and intravenous sedation (p=0.02)
      but not with intracameral lidocaine or other tested variables. However, odds
      ratio for pain increased to 5.1 (95% CI; 1.29-20.41) in participants without
      intravenous sedation compared to those with sedation. CONCLUSIONS: The results of
      the present study suggest that intravenous sedation preoperatively seems to be an
      important determinant to relieve the sensation of discomfort/pain during small
      incision cataract surgery, but intracameral lidocaine was shown not to have a
      clinically useful role.

PMID- 17534813
TI  - Phacoemulsification in vitrectomized eyes under topical anesthesia.
AB  - PURPOSE: To study phacoemulsification in vitrectomized eyes under topical
      anesthesia, assessing anesthetic and intraoperative characteristics and
      complications. METHODS: A prospective study was performed on 52 eyes of 51
      patients who underwent phacoemulsification of cataract with intraocular lens
      implantation under topical anesthesia, having previously undergone pars plana
      vitrectomy. Surgical and anesthetic observations and complications were recorded,
      as were visual outcomes. RESULTS: Ninety-two percent of patients had improved
      visual acuity postoperatively with only one patient having visual loss as a
      result of surgery. The most common intraoperative observations were of a deep
      anterior chamber, posterior capsular plaques, posterior synechiae, and nuclear
      sclerotic cataracts. Topical anesthesia proved satisfactory in 96%, with only two
      patients requiring intracameral lignocaine 1%; no patients required conversion to
      injection anesthesia. There were no major operative or postoperative
      complications. CONCLUSIONS: Phacoemulsification in vitrectomized eyes can be
      challenging, but is visually rewarding. Topical anesthesia proved satisfactory
      for the vast majority of cases, with none of our patients requiring conversion to
      injection anesthesia.

PMID- 17534814
TI  - Ocular symptoms and signs with preserved and preservative-free glaucoma
      medications.
AB  - PURPOSE: To compare the prevalence of side effects between eyedrops with or
      without preservatives, in terms of subjective symptoms and objective signs in
      patients with open-angle glaucoma. METHODS: In a multicenter cross-sectional
      epidemiologic survey in four European countries, ophthalmologists in private
      practice enrolled 9658 nonconsecutive patients using preservative (P) or
      preservative-free (PF) beta-blocking eyedrops between June 1997 and December
      2003. Subjective symptoms, conjunctival and palpebral signs, and superficial
      punctate keratitis were explored before and after a change in therapy. For
      statistical analysis, a Chi-square test was used to calculate the differences in
      the prevalence of symptoms and signs with or without preservatives. RESULTS: A
      total of 74% of the patients used P, 12% PF, 10% a P-PF combination, and in 4%
      the type of medication was unknown. Each recorded symptom and all the palpebral,
      conjunctival, and corneal signs were significantly more frequent (p<0.0001) in
      the P-group than in the PF-group, such as pain or discomfort during instillation
      (48 vs 19%), foreign body sensation (42 vs 15%), stinging or burning (48 vs 20%),
      and dry eye sensation (35 vs 16%). A total of 68% of the patients had a sec-ond
      visit performed, of whom 63% (6083) had been evaluated on treatment difference. A
      significant decrease (p<0.0001) of all ocular symptoms and signs was observed in
      patients in whom the preserved eyedrops were diminished in number or altered into
      preservative free drops. CONCLUSIONS: Compared to preserved eyedrops,
      preservative free eyedrops are significantly less associated with ocular symptoms
      and signs of irritation.

PMID- 17534815
TI  - Influence of deep scleral flap size on intraocular pressure after deep
      sclerectomy.
AB  - PURPOSE: To study the effect of several morphometric characteristics of the deep
      scleral flap on intraocular pressure (IOP) control after deep sclerectomy.
      METHODS: The authors conducted a nonrandomized prospective study of 56 eyes of 51
      patients who underwent deep sclerectomy alone or combined with
      phacoemulsification. A reticulated hyaluronic acid implant was used in all cases.
      The surface, volume, and weight of the dissected deep scleral flap were measured
      and recorded. The correlation between these parameters and the postoperative IOP
      was evaluated at 6 and 12 months postoperatively. RESULTS: Forty-nine eyes
      (87.50%) achieved an IOP of 21 mmHg or less without treatment, and the need for
      medication was decreased significantly (p<0.001) at 12 months postoperatively.
      The authors found a significant inverse correlation between the mean
      postoperative IOP at 6 months and the surface, volume, and weight of the deep
      scleral flap, but not at 12 months postoperatively. CONCLUSIONS: Greater weight,
      surface area, and volume of the deep scleral flap dissected during deep
      sclerectomy achieve significantly lower postoperative IOPs in the early
      postoperative period.

PMID- 17534816
TI  - Impact of intraocular pressure after filtration surgery on visual field
      progression in primary open-angle glaucoma.
AB  - PURPOSE: To compare visual field progression after trabeculectomy in eyes showing
      a postoperative intraocular pressure (IOP) less than or equal to 16 mmHg and eyes
      with an IOP of 17 to 21 mmHg. METHODS: A retrospective cohort study design was
      used. A total of 101 eyes of 101 consecutive patients undergoing trabeculectomy
      for primary open-angle glaucoma (POAG) with a postoperative IOP less than or
      equal to 21 mmHg were divided into two groups: Group 1 included eyes showing a
      postoperative IOP less than or equal to 16 mmHg at all visits and Group 2
      included eyes with a postoperative IOP between 17 and 21 mmHg. In turn, each of
      these groups was divided into two subgroups according to whether treatment was
      required for IOP control. Glaucomatous visual field control during follow-up was
      compared between the subject groups. RESULTS: Kaplan-Meier analysis revealed
      glaucomatous visual field control in 98.53% of the eyes in Group 1 and 89.06% of
      those in Group 2 at 5 years, the difference between the groups being significant.
      CONCLUSIONS: Glaucomatous disease progression is less frequent when IOP is less
      than or equal to 16 mmHg in all the follow-up visits after trabeculectomy. The
      results indicate a definite benefit of low IOP in visual field control.

PMID- 17534817
TI  - Anterior segment optical coherence tomography for evaluation of changes in
      anterior chamber angle and depth after intraocular lens implantation in eyes with
      glaucoma.
AB  - PURPOSE: To examine anterior chamber depth (ACD) and anterior chamber angle (ACA)
      in patients with glaucoma after cataract extraction with an anterior optical
      coherence tomography (OCT) system. METHODS: A new commercially available 1310 nm
      infrared light anterior segment OCT system was used for anterior chamber
      evaluation. Sixty patients (n=20 with primary open angle glaucoma [POAG], n=20
      with angle closure glaucoma [ACG], and n=20 with no known glaucoma as control
      group) with a mean age of 68.8+/-13.9 years undergoing cataract surgery were
      enrolled. RESULTS: Before cataract surgery, ACD and ACA of the ACG group were
      significantly lower compared to the POAG and control groups (ACD p<0.005; ACA
      p<0.005). After cataract extraction, ACD and ACA increased significantly in the
      ACG group (3.1+/-0.4 mm vs 1.8+/-0.2 mm, p<0.005 and 32.3 degrees +/-7.7 degrees
      vs 16.0 degrees +/-4.7 degrees , p<0.005). In the POAG and control groups, ACD
      and ACA also increased postoperatively, but not as much as in the ACG group.
      After cataract extraction, IOP decreased significantly in the glaucoma groups
      (ACG: 15.6+/-6.1 vs 18.6+/-5.7 mm Hg, p=0.008; POAG: 16.2+/-3.4 vs 20.7+/-8.0
      mmHg, p=0.02) and was almost the same in all three groups after surgery (control
      group after surgery: 15.2+/-2.8 mmHg). CONCLUSIONS: Both ACD and ACA increased
      significantly after cataract extraction and IOL implantation. IOP reduction after
      surgery was higher in the glaucoma groups compared to the control group.

PMID- 17534818
TI  - Penetration of betaxolol HCL ionic suspension 0.25% and betaxolol HCL solution
      0.50% into the aqueous humor.
AB  - PURPOSE: To determine the intraocular penetration of topical drops of betaxolol
      HCl 0.25% suspension and betaxolol HCl 0.50% solution into the aqueous humor.
      METHODS: Fifteen patients were randomly assigned to receive topical betaxolol HCl
      0.25% suspension (n=7) or topical betaxolol HCl 0.50% solution (n=8) the day
      before cataract surgery. Aqueous samples were collected 2 hours after the
      administration of the morning dose during cataract surgery. Drug concentrations
      were determined by high-performance liquid chromatography with fluorescence
      detection. RESULTS: The mean aqueous humor concentration of topical betaxolol HCl
      0.25% suspension was 275.1+/-168.8 micro g/mL (range 570-70 micro g/mL) and the
      mean aqueous humor concentration of topical betaxolol HCl 0.50% solution was
      195.4+/-102.4 micro g/mL (range 334-50 micro g/mL) (p=0.281). CONCLUSIONS: The
      mean aqueous humor concentration of betaxolol 0.25% suspension was higher than
      betaxolol 0.50% solution; however, the difference was not statistically
      significant. With twofold reduced concentration and similar anterior chamber
      penetration, betaxolol 0.25% suspension could be first choice for Beta 1
      selective blocker therapy when considered for patients with glaucoma.

PMID- 17534819
TI  - Aqueous and vitreous penetration of levofloxacin after topical and/or oral
      administration.
AB  - PURPOSE: To investigate the aqueous and vitreous penetration of levofloxacin, the
      drug was administered topically and/or orally to patients undergoing vitrectomy.
      METHODS: Thirty-six patients undergoing initial vitrectomy with
      phacoemulsification and aspiration (PEA) were enrolled, and were divided randomly
      into three groups. Group 1 was treated with topical application of levofloxacin
      (three times on the day before surgery and seven times on the day of surgery),
      Group 2 received oral administration of levofloxacin (200 mg twice on the day
      before surgery and 200 mg at 3 hours before surgery), and Group 3 received both
      topical and oral levofloxacin according to the above schedules. The concentration
      of levofloxacin was measured in aqueous humor and vitreous fluid samples obtained
      during surgery. RESULTS: In Groups 1, 2, and 3, the mean levofloxacin
      concentration in aqueous humor was 0.765+/-0.624 micro g/mL, 1.279+/-0.440 micro
      g/mL, and 1.823+/-0.490 micro g/mL, respectively, while the mean levofloxacin
      concentration in vitreous fluid was <0.02 micro g/mL, 1.455+/-0.445 micro g/mL,
      and 1.369+/-0.530 micro g/mL, respectively. CONCLUSIONS: Oral administration of
      levofloxacin at a dose of 400 mg/day was sufficient for the prophylaxis of ocular
      infections, because the drug concentrations in both aqueous humor and vitreous
      fluid were higher than the MIC90 values for major ocular pathogens. Topical
      application of levofloxacin achieved adequate drug levels in aqueous humor, but
      not in vitreous fluid, while combined topical and oral administration had an
      additive effect on the drug concentration in aqueous humor.

PMID- 17534820
TI  - Optic nerve alterations in P27(Kip1) knockout mice.
AB  - PURPOSE: To study the morphologic characteristics of the optic nerve (ON) by
      using an experimental model of knockout mice for the expression of the P27(Kip1)
      gene, mainly involved in cell cycle arrest, apoptosis control, and retinoblastoma
      protein phosphorylation. METHODS: Eyeballs with the retrobulbar ON attached were
      obtained from 26-week-old mice. By using morphologic and morphometric techniques,
      light and electron transmission microscopy, the ON characteristics were
      determined in two groups of mice: 1) wild type mice as the control group (n=15),
      2) homozygous knockout mice (-/-) for the P27(Kip1) gene as the knockout group
      (n=15). Glial fibrillary acidic protein (GFAP) and myelin basic protein (MBP)
      were studied using Western blot and immunoblotting approaches. RESULTS: The ON
      cross-sectional area was significantly larger in the P27(Kip1) knockout mice
      group than in the control group (p<0.001). The axon sizes in knockout animals
      were much larger than in wild-type mice (p<0.001). Higher number of axons forming
      the ON, intra-axonal degeneration, myelin sheath, and axoplasm density
      alterations were found in P27(Kip1) knockout mice when compared with control
      group (p<0.001). Analysis of lysates of optic nerves by Western blot showed less
      expression of myelin basic protein and GFAP in P27(Kip1) knockout mice as
      compared to wild type mice (p<0.005, p<0.01, respectively). CONCLUSIONS: The
      morphologic and morphometric results suggest that homozygous P27(Kip1) knock-out
      mice had hypertrophic, hyperplastic, and dystrophic ON.

PMID- 17534821
TI  - Biometric indices evaluation in central retinal vein occlusion using partial
      coherence laser interferometry.
AB  - PURPOSE: To evaluate the association of axial length and posterior segment length
      with central retinal vein occlusion (CRVO) using optical coherence
      interferometry. METHODS: The study group consisted of 29 patients (13 female and
      16 male) with unilateral CRVO who were referred to Farabi Eye Hospital. Patients
      with macular edema were excluded. The mean keratometry (mean K), axial lengths
      (AL), anterior chamber depths (ACD), and posterior segment lengths (PSL, defined
      by AL - ACD) of affected and fellow eyes were measured using optical coherence
      interferometry. RESULTS: Age range was 45 to 74 years (mean 59.2 +/- 7.5 years).
      The mean K of affected eyes was not statistically significantly lower than that
      of unaffected eyes in the CRVO group. This was also true for ACD. Although
      affected eyes had shorter axial length (23.26 mm vs 23.33 mm), the difference was
      not significant. There was a statistically significant difference in PSL affected
      and unaffected eyes (20.15 mm vs 20.26 mm) (p=0.008). CONCLUSIONS: Posterior
      segment length of eyes with CRVO may be shorter than unaffected eyes. This may
      predispose them to more crowding of central retinal vein and artery in lamina
      cribrosa, and developing CRVO.

PMID- 17534822
TI  - Long-term clinical outcomes and therapeutic benefits of triamcinolone-assisted
      pars plana vitrectomy for proliferative vitreoretinopathy: a case study.
AB  - PURPOSE: To investigate intraoperative visibility and long-term clinical outcome
      following triamcinolone acetonide (TA)-assisted pars plana vitrectomy (PPV) for
      proliferative vitreoretinopathy (PVR). METHODS: A retrospective interventional
      noncomparative clinical study was carried out on 21 eyes from 21 patients with
      more than grade C2 PVR, all of whom underwent TA-assisted PPV. Two of the
      specimens were observed with an electron microscope. After treatment, outcome
      measures, including changes in best-corrected visual acuity (BCVA), intraocular
      pressure (IOP) elevation, corneal pathology, and occurrence of endophthalmitis,
      were recorded. Patient follow-up time was >36 months (mean +/-standard deviation
      = 47.3 +/- 6.7 months). RESULTS: TA improved the intraoperative visualization of
      the epiretinal membrane (ERM), allowing it to be easily removed together with the
      partially internal limiting membrane (ILM) using micro forceps. The excised
      tissue consisted of proliferative cells and an extracellular matrix underlying
      the ILM. After the operation, 71.4% of the eyes had improved BCVA. Three of the
      eyes showed sustained IOP elevation (14.3%); two of these cases were controlled
      by the administration of eyedrops, while the third required filtering surgery. In
      two cases, an absorption delay of the TA granule on the retinal surface was
      observed. One eye developed corneal stromal opacity. No other severe
      complications occurred during the observation period. CONCLUSIONS: TA-assisted
      PPV offers improved visualization during the surgical management of PVR, and
      allows surgeons to excise the ERM safely and effectively without the risk of
      serious complications.

PMID- 17534823
TI  - Extrusion and infection incidence in scleral buckling surgery with the use of
      silicone sponge: to soak or not to soak? An 11-year retrospective analysis.
AB  - PURPOSE: To assess the incidence of extrusion and infections of encircling
      silicone sponges in scleral buckling surgery for retinal detachment with and
      without the use of an intraoperative antibiotic soaking procedure. METHODS: The
      authors performed a retrospective analysis reviewing the charts of 1127 patients
      who underwent episcleral buckling surgery operated by the same surgeon in three
      different institutions during a period of 11 years. The authors reviewed the
      charts of patients treated with a single episcleral silicone sponge (Labtician)
      indentation in three different models. The infection prophylaxis on the operating
      field was the same in all cases and only since February 1997 was the silicone
      sponge preoperatively treated with an antibiotic soaking procedure. RESULTS: No
      immediate postoperative infections were reported in the operated eyes. Three eyes
      had an implant extrusion and in all these cases silicone sponge removal was
      performed. All three extrusion cases developed when sponge soaking was not
      adopted. CONCLUSIONS: The data indicate that the soaking procedure does not
      decrease extrusion and infection incidence in scleral buckling surgery when both
      accurate surgical technique and disinfection prophylaxis are performed.

PMID- 17534824
TI  - Serum prolactin levels and Behcet disease.
AB  - PURPOSE: To evaluate serum prolactin levels in Behcet disease (BD) and correlate
      with phenotypic expression of the disease. METHODS: This was a prospective,
      nonrandomized comparative trial. Twenty-two patients fulfilling BD Research
      Committee criteria and 21 healthy control subjects were included. Patients were
      classified in complete-type or incomplete-type BD subgroups according to clinical
      characteristics such as recurrent oral ulcers, genital ulcers, skin lesions, and
      ocular disease. Age, sex, HLA phenotyping, and therapy were recorded for
      comparative analysis between groups. Serum prolactin levels were determined by
      electrochemiluminescence immunoassay on a Modular Analytics E170 analyzer.
      RESULTS: Prolactinemia was significantly higher (mean=19.34 ng/mL) in BD patients
      vs controls (mean=9.83 ng/mL) (p=0.009). This value was also statistically higher
      in complete-type BD sub-group vs controls (p=0.02). Younger patients (<30 y)
      required corticosteroids plus immunosuppressives more often (75%), suggesting an
      association between age and disease severity, al-though not statistically
      significant. CONCLUSIONS: Results suggest the role of prolactin in BD
      pathogenesis and its association with disease expression, especially in complete
      type BD.

PMID- 17534825
TI  - Complications of hydroxyapatite pegging: comparison between polycarbonate and
      titanium peg system.
AB  - PURPOSE: Polycarbonate peg has been customarily used for pegging of
      hydroxyapatite for years. For better movement, tissue tolerance, and to decrease
      the complications of pegging, titanium peg system has been used. This study
      compares the two systems. METHODS: Complications associated with pegging
      (polycarbonate: Bio-Eye or titanium: Dr-Perry new P-K) were retrospectively
      reviewed from the charts of 153 patients admitted to the Labbafinejad Medical
      Center, Tehran, Iran, for over 5 years from 1997 to 2003. RESULTS: A total of 153
      cases were studied. Ninety-six (62.3%) were male and 57 (37.7%) were female, and
      the mean age was 27.7 years (6-59 years). In 88 cases pegs were poly-carbonate
      and sleeve system and in 65 cases pegs were titanium. Forty-one (46%) of cases
      with polycarbonate and 18 (27%) of cases with titanium had at least one or more
      complications (p=0.018). The most common complications were granulation tissue,
      discharge, overgrowth of conjunctiva, and peg falling out in 25%, 23%, 13%, and
      8% in polycarbonate peg and 15%, 5%, 1.5%, and 0% in titanium peg group. The
      prevalence of the last three complications was statistically lower in titanium
      peg compared with polycarbonate. Twenty-five cases (35%) with polycarbonate peg
      and 5 cases (7.5%) with titanium peg had two or more complications (p=0.03). Peg
      removal was done in 11 cases of polycarbonate but only two cases of titanium peg
      in order to treat the complication. CONCLUSIONS: Both pegging systems had some
      complications, although these were less severe and prevalent in titanium peg.
      More studies on complications due to titanium pegs are recommended.

PMID- 17534826
TI  - Triaging and coding ophthalmic emergency: the Rome Eye Scoring System for Urgency
      and Emergency (RESCUE): a pilot study of 1,000 eye-dedicated emergency room
      patients.
AB  - PURPOSE: Ophthalmic emergency (OE) triage is essential for prompt recognition of
      urgent cases. To date, no formal eye-dedicated triaging system has been widely
      accepted. The purpose of the present study is to propose a fast, accurate, and
      reproducible coding scale called the Rome Eye System for Scoring Urgency and
      Emergency (Rescue). METHODS: Phase 1 of the study is a retrospective analysis of
      electronic medical records (EMR); phase 2 is a prospective consecutive series.
      Phase 1 included 160,936 patients. Phase 2 included 1000 consecutive patients
      referred to the emergency department (ED) of our institution. In phase 1, the
      authors retrospectively analyzed EMRs of patients presenting to the ED, listing
      signs and symptoms most frequently associated with hospitalization. Redness,
      pain, loss of vision, and the risk for an open eye were identified and assigned a
      score ranging from 0 to 12. Color coding was assigned based on increasing
      scoring: 0-3 white, 4-7 green, 8-12 yellow code. In phase 2, 1000 consecutive ED
      patients were enrolled and prospectively coded according to RESCUE. After
      diagnosis and proper treatment, EMRs were retrospectively reviewed by a masked
      physician and patients recoded (Retro coding) according to clinical course.
      Correlation between Rescue and Retro coding was calculated. MAIN OUTCOME
      MEASURES: Prospective and retrospective ED color coding correlation. RESULTS: A
      total of 160,936 EMR were retrospectively analyzed; 2407 (1.4%) patients required
      hospitalization. Loss of vision (90%), redness (76%), and pain (47%) were the
      most frequent complaints. Rescue significantly correlated to Retro coding
      (p<0.01): 841/1000 patients coded exactly the same color, 45/1000 were
      overestimated by one color class, none by two, 107/1000 underestimated by one,
      and 6/1000 by two classes. The 32/1000 hospitalized patients in the prospective
      cohort had a Rescue score significantly higher than non-admitted patients
      (p<0.01) and color coding among admitted and dismissed patients was significantly
      different as well (p<0.01). CONCLUSIONS: The Rescue system seems promising in
      terms of usefulness and ease of implementation. The high correlation between
      Rescue code assigned prospectively and the post-diagnosis coding, as well as the
      prompt discrimination of cases that eventually required hospitalization, may lead
      to a wider use of the Rescue system. Further testing on larger samples and
      different institutions is warranted.

PMID- 17534827
TI  - Magnitude and causes of unilateral absolute blindness in a region of Oman: a
      hospital-based study.
AB  - PURPOSE: To report the magnitude and causes of unilateral absolute blindness (no
      light perception) and barriers faced by persons with unilateral blindness in the
      South Batinah region of Oman. METHODS: Between January and June 2002, 12,000
      patients were evaluated for visual acuity, ocular pressure, anterior ocular
      biomicroscopic examination, and posterior segment indirect ophthalmoscopy
      examination by ophthalmologists at Al Rustaq hospital in Oman. Patients having no
      perception of light in at least one eye were included in the cohort. A closed
      ended questionnaire was used to collect data on the personal profile, history of
      blindness, barriers perceived as the cause of blindness, and participants'
      attitude towards eye care and quality of life following visual disability.
      RESULTS: In the 12,000 patients studied, absolute unilateral blindness (no
      perception of light) was present in 122 persons, a rate of 1.0% in our series.
      The onset of blindness was gradual in 78 (63.9%) persons and 64 (54.9%) persons
      had unilateral blindness for more than 10 years. The main causes of blindness e
      phthisis/absent/disorganized blind eye, which was present in 64 (52.5%) persons;
      glaucoma, seen in 49 (40.2%) participants; and corneal opacity, seen in 8 (6.5%)
      persons. Eighty 4.8%) persons had <3/60 vision in the fellow eye. Thirty (24.6%)
      persons had cataract and 19 (15.6%) persons glaucoma in the fellow eye. Forty
      eight (39.3%) persons had undergone cataract surgeries while 2 (1.6%) persons
      were operated for glaucoma in the fellow eye. Lack of access to ophthalmic
      services and use of traditional medicines during the onset of blindness were
      reported by nearly half of the cohort. The attitude towards blindness was
      negative in two thirds of subjects. CONCLUSIONS: Cataract and glaucoma were
      important determinants of visual impairment in the fellow eyes of this cohort.
      These patients are at higher risk of developing bilateral impairment and need
      special care to prevent/treat visual disabilities in the fellow eyes. Using
      appropriate services, one can attempt attitudinal changes, rehabilitate them, and
      create a positive attitude towards life.

PMID- 17534828
TI  - Lattice corneal dystrophy type II: clinical, pathologic, and molecular study in a
      Spanish family.
AB  - PURPOSE: To report a family with lattice corneal dystrophy type II (LCD II)
      associated with systemic amyloidosis type V. METHODS: A 69-year-old woman
      presented a LCD II and marked dermachalasis. A lower blepharoplasty was
      performed. Two years later a penetrating keratoplasty was performed in her left
      eye. Three children of the patient were studied. Subtle manifestations of LCD
      were identified in two of them. Pathologic study of the excised skin and corneal
      button was made. DNA from peripheral blood was obtained, and was subjected to
      amplification of exon 5 of the gelsolin. RESULTS: Pathologic examination of the
      skin of blepharoplasty specimen demonstrated the presence of amyloid. Microscopic
      examination of the corneal button showed the presence of amyloid deposits beneath
      the normal-appearing Bowman layer and also within the stroma. Immunostaining for
      S-100 protein did not demonstrate a significant relationship between amyloid
      deposits and corneal nerves. Electron microscopic evaluation demonstrated the
      presence of amyloid fibrils. No clear relationship was found between amyloid
      deposits and corneal nerves. These findings confirm LCD type II or Meretoja
      syndrome. A mutation analysis of the gelsolin gene demonstrated the presence of G
      to A transition at nucleotide 654. Two children with manifestations of LCD also
      showed the identical mutation in gelsolin gene. CONCLUSIONS: A new family with
      Meretoja syndrome is reported. This is the first documented family with Meretoja
      syndrome in Spain and in the Mediterranean countries. The molecular study shows
      the same mutation of reported families from Finland, Japan, the United States,
      and the United Kingdom.

PMID- 17534829
TI  - Unilateral corneal endothelial dystrophy and anterior keratoconus.
AB  - PURPOSE: To describe a case of keratoconus and Fuchs' corneal endothelial
      dystrophy in the left eye with no corneal disease in the right eye. METHODS: A 64
      year-old woman presented with visual impairment in her left eye; computer
      assisted topographic analysis and specular microscopy were performed in both eyes
      and left cornea was histopathologically examined. RESULTS: Keratoconus was
      diagnosed by slit-lamp examination, keratometry, and computer-assisted
      topographic analysis. Corneal endothelial dystrophy was diagnosed on the basis of
      clinical examination and specular microscopy. Histopathologic examination
      revealed a stromal degeneration typical of keratoconus and a non-guttae form of
      endothelial dystrophy. CONCLUSIONS: This is a rare case of unilateral corneal
      endothelial dystrophy and keratoconus.

PMID- 17534830
TI  - Rapid development of band keratopathy of corneal graft associated with treatment
      with intracameral recombinant tissue plasminogen activator for postoperative
      fibrin reaction.
AB  - PURPOSE: To report a corneal transplant complication associated with intracameral
      recombinant tissue plasminogen activator (rTPA) treatment of postoperative fibrin
      reaction. METHODS: In a 71-year-old patient, a triple procedure was performed for
      perforated rheumatic ulcer and secondary cataract. RESULTS: A dense band
      keratopathy developed rapidly within 36 hours after the use of intracameral
      injection of rTPA for the treatment of a dense fibrin clot. CONCLUSIONS: This is
      the first report of rapid development of massive band keratopathy in a corneal
      graft after triple procedure and treatment with intracameral rTPA. Intracameral
      rTPA should be used with caution in patients with attenuated endothelium.

PMID- 17534831
TI  - Ahmed valve for elevated intraocular pressure associated with black diaphragm
      lenses for aniridia.
AB  - PURPOSE: To evaluate the Ahmed valve for decrease elevated pressure associated
      with black diaphragm lenses for aniridia. METHODS: Drainage devices are useful to
      obtain good control of intraocular pressure in patients with aniridia and the
      authors often use them because of the poor results of medical therapy or
      filtering surgery. However, when the elevated intraocular pressure is associated
      with black diaphragm lenses for aniridia, most authors decide to carry out a
      filtering technique. The current authors opted for the implantation of an Ahmed
      valve in three patients, two with traumatic aniridia and the other with a
      congenital case. Every patient had a different kind of black diaphragm lens for
      aniridia. RESULTS: The Ahmed valve controlled the intraocular pressure in levels
      below 20 mmHg for a follow-up year with no complications derived from its
      application. CONCLUSIONS: Ahmed valve implantation was the best technique to
      decrease intraocular pressure in patients with aniridia. The authors have used it
      successfully for cases with elevated pressure associated with black diaphragm
      lenses for aniridia.

PMID- 17534832
TI  - Macular sensitivity change in multiple sclerosis followed with microperimetry.
AB  - PURPOSE: To describe the efficacy of MP-1 in detecting early multiple sclerosis
      (MS) retinal lesions and in monitoring the effectiveness of treatment in terms of
      changes in macular sensitivity. METHODS: A 21-year-old woman with MS was referred
      to us complaining of recurrent episodes of eyesight loss in both eyes. At
      ophthalmologic examination, best-corrected visual acuity was 20/25 bilaterally;
      ophthalmoscopy showed bilateral slight optic neuritis without swelling of the
      disc. Static perimetry of central visual field (30 degrees, by Octopus 101, Haag
      Streit AG, Switzerland) and retinal sensitivity of the 12 central degrees (by MP
      1 Micro Perimeter, Nidek Inc., Italy) were performed on the patient at that time.
      The micro perimeter (MP-1) showed a loss of sensitivity in the macular region
      with 0.28+/-0.9 dB sensitivity in the right eye and 19.42+/1.5 dB in the left.
      The mean fixation stability was 91% considering 2 degrees and 99% considering 4
      degrees around the fixation points in the right eye, and 97% in 2 degrees and
      100% in 4 degrees central degrees in the left. In the weeks that followed vision
      continued to get worse in both eyes, so she underwent a steroid therapy with
      methylprednisolone IV 1000 mg/day for 5 days and 500 mg/day for 3 days. RESULTS:
      After 8 days of therapy the MP-1 showed a significant recovery in the right eye,
      with mean light sensitivity being 19.61+/-1.3 dB in the right eye and 20.0+/-0 dB
      in the left eye in both macular and peripapillary regions. The mean fixation
      stability was 100% considering 2 degrees and 100% considering 4 degrees around
      the fixation points in both eyes. CONCLUSIONS: The MP-1 can be an interesting
      tool for neuro-ophthalmologists as it allows a more precise evaluation of the
      macular and peripapillary region, which is not easily studied with conventional
      automated perimetry. In MS, the presence of a subclinical form of optic nerve
      involvement can be demonstrated in a very early stage, and well followed by the
      introduction of micro perimeter testing in the standard examination protocol.

PMID- 17534833
TI  - Actinomyces neuii subspecies anitratus chronic endophthalmitis after cataract
      surgery.
AB  - PURPOSE: To report a case of unusual chronic endophthalmitis by Actinomyces neuii
      subspecies anitratus. METHODS: A 75-year-old man underwent uneventful
      phacoemulsification with implantation of a foldable posterior chamber intraocular
      lens in his right eye. Four weeks after surgery, a chronic post-operative
      endophthalmitis characterized by anterior chamber and vitreous cellular debris
      developed in this eye. Cultures were positive, and A neuii subspecies anitratus
      was identified by polymerase chain reaction and subsequent rRNA sequence
      analysis. Immediate treatment included intravitreal and intensive topical
      antibiotics along with oral ciprofloxacin. RESULTS: The condition improved
      rapidly, and 6 months after surgery the patient was asymptomatic, the best
      spectacle-corrected visual acuity was 20/22, and the anterior chamber was quiet.
      CONCLUSIONS: A neuii subspecies anitratus should be considered in the
      differential diagnosis of chronic endophthalmitis after cataract surgery.
      Polymerase chain reaction and subsequent RNA typing were useful in detecting the
      causative organism, and intravitreal antibiotics were successful.

PMID- 17534834
TI  - Curvilinear streaks in multifocal choroiditis.
AB  - PURPOSE: Discreet chorioretinal spots, neovascular maculopathy, peripapillary
      atrophy and peripheral curvilinear pigmentary-atrophic streaks are characteristic
      of Multifocal Choroiditis. We report the presence of curvilinear streaks in the
      posterior pole. METHODS: Observational series. RESULTS/CONCLUSIONS: Like
      chorioretinal discreet spots, peripheral curvilinear atrophic-pigmentary streaks
      may also appear in the posterior fundus, including the macular region, in
      Multifocal Choroiditis.

PMID- 17534835
TI  - Macular hole and intravitreal injection of triamcinolone acetonide for macular
      edema due to central retinal vein occlusion.
AB  - PURPOSE: To report a case of macular hole progression after intravitreal
      injection of triamcinolone acetonide (IVTA) for chronic macular edema secondary
      to nonischemic central retinal vein occlusion (CRVO). METHODS: A 33-year-old
      woman with massive macular edema after CRVO underwent IVTA. Optical coherence
      tomography (OCT) and fluorescein angiography were performed before and after the
      procedure. RESULTS: At the 1-week IVTA injection control, the patient's best
      corrected visual acuity improved from 20/400 to 20/200 and OCT detected a
      progression of macular hole stage. CONCLUSIONS: IVTA steroid injection may
      provide a significant improvement in macular edema, but injection-related
      complications may occur such as this uncommon macular reaction resulting in
      permanent visual loss.

PMID- 17534836
TI  - Optic nerve compartment syndrome in a patient with optic nerve sheath meningioma.
AB  - PURPOSE: To report a patient with optic nerve (ON) sheath meningioma, unilateral
      optic disc swelling, and inhomogeneous cerebrospinal fluid (CSF) composition
      between lumbar CSF and CSF from the subarachnoid space (SAS) of the affected ON.
      METHODS: A 39-year-old woman presented with unilateral optic disc swelling and
      slight deterioration of visual function in the left eye. Extensive laboratory
      workup and magnetic resonance imaging (MRI) of the brain and orbits were
      performed. As radiotherapy was refused by the patient, ON sheath fenestration
      (ONSF) was offered and performed in order to stop deterioration. CSF from the SAS
      of the ON was sampled. RESULTS: Laboratory workup was within normal limits. MRI
      of the left orbit demonstrated enhancement of the dura in the precanalicular
      portion of the ON and distension of the SAS, most prominent in the bulbar portion
      of the ON. On lumbar puncture the opening pressure measured 19 (cm H2O). Compared
      to the lumbar CSF the CSF of the affected ON SAS showed markedly elevated
      measurements for albumin, IgG, and beta-trace protein. Visual function remained
      stable over a follow-up time of 18 months. CONCLUSIONS: Composition of CSF is
      considered to be homogenous throughout all CSF spaces. In this patient the
      authors found a marked concentration-gradient of albumin, IgG, and beta-trace
      protein between the CSF in the spinal canal and the CSF in the SAS of the
      affected ON. Based on the radiologic features of the left ON and the dissociated
      beta-trace protein concentrations in the CSF of the SAS of the ON and the lumbar
      CSF, the diagnosis of an ON sheath compartment syndrome due to an ON sheath
      meningioma was made.

PMID- 17534837
TI  - Incidence of nonarteritic anterior ischemic optic neuropathy in adult Chinese:
      the Beijing Eye Study.
AB  - PURPOSE: To determine the incidence of optic nerve damage due to nonarteritic
      anterior ischemic optic neuropathy (NAION) in the adult Chinese population.
      METHODS: The Beijing Eye Study, a population-based, longitudinal study which
      included 4439 subjects (age 40+ years) in 2006, was repeated in 2006. In the
      follow-up examination, 3169 (71.4%) subjects participated. Optic disc photographs
      were assessed. Diagnostic criteria for incident NAION were a small optic disc,
      segmental pallor, and loss of retinal nerve fiber layer and visual field in the
      follow-up examination, with a normal optic nerve head appearance at baseline.
      RESULTS: New NAION was found in one eye, with an incidence rate of 0.03+/-0.03%
      per 5 years (mean +/- standard error) (95% confidence interval: -0.03, 0.09), or
      about 1:16,000 subjects per year. CONCLUSIONS: Within a 5-year period, new NAION
      may develop in 1 out of 3200 adult Chinese, or 1:16,000 adult Chinese per year.

PMID- 17534838
TI  - Endogenous Pseudomonas endophthalmitis in an immunocompetent patient.
AB  - PURPOSE: To report an unusual case of community-acquired Pseudomonas aeruginosa
      pneumonia in an immunocompetent host complicated by orbital cellulitis,
      panophthalmitis, and subcutaneous nodules. METHODS: An otherwise healthy 47-year
      old woman presented with a 24-hour history of fever, cutaneous nodules, right
      sided pleuritic chest pain, and eyelid edema with severe vision loss in her right
      eye. A chest X-ray demonstrated a homogeneous infiltrate in the right upper lobe.
      Ophthalmic examination revealed signs of metastatic orbital cellulitis and
      panophthalmitis. Culture specimens from blood, sputum, skin, and vitreous showed
      a significant growth of P. aeruginosa species. RESULTS: Intravenous antibiotic
      therapy led to resolution of the pneumonia, cutaneous nodules, and orbital
      cellulitis. Despite intravitreal and topical antibiotics, the patient finally
      required enucleation. CONCLUSION: This case represents a rare combination of
      manifestations in an immunocompetent patient with P. aeruginosa infection. It
      highlights the accelerated course that may result from P. aeruginosa infection,
      the difficulties of treatment, and the poor prognosis in the case of eye
      involvement.

PMID- 17534840
TI  - Phakic intraocular lenses after scleral buckling for retinal detachment.
AB  - PURPOSE: To assess efficacy and safety of angle-supported phakic intraocular
      lenses (PIOL) implanted after scleral buckling for retinal detachment. SETTING:
      Private practice in Siena, Italy. METHODS: Retrospective, noncomparative
      consecutive case series. Inclusion criteria for retrospective evaluation were
      previous uncomplicated external retinal detachment surgery (scleral buckling),
      and a complete follow-up superior to 3 years from PIOL implantation. RESULTS:
      Nine eyes of seven patients were included. Mean time interval between retinal
      detachment surgery and PIOL implantation was 3.2 years +/- 4.5 (range 1 to 15).
      Mean spherical equivalent (SE) before PIOL implantation was -16.36 D +/- 3.98;
      range: -11.75 to -23. PIOL surgery was uneventful in all cases. Mean SE after
      PIOL implantation was -0.99+/-0.51 (95% confidence interval for the mean: -0.59
      to -1.39). Mean follow-up after PIOL implantation was 4.2 years +/- 0.8 (range 3
      to 5). Complications were pupil ovalization (inferior to 1 mm) in two eyes, and
      worsening of floaters in both eyes of one patient. No recurrences of retinal
      detachment were observed. CONCLUSIONS: In selected eyes with no anterior chamber
      abnormalities, the implantation of angle supported PIOL after scleral buckling
      for retinal detachment is associated with good refractive results and minor
      complications.

PMID- 17534841
TI  - Diallyl disulphide depletes glutathione in Candida albicans: oxidative stress
      mediated cell death studied by two-photon microscopy.
AB  - Using two-photon scanning laser microscopy, we investigated the effect of an
      Allium sativum (garlic) constituent, diallyl disulphide (DADS), on key
      physiological functions of the opportunistic pathogen Candida albicans. A short
      30 min exposure to 0.5 mM DADS followed by removal induced 70% cell death (50%
      necrotic, 20% apoptotic) within 2 h, increasing to 75% after 4 h. The early
      intracellular events associated with DADS-induced cell death were monitored with
      two-photon fluorescence microscopy to track mitochondrial membrane potential
      (Deltapsi(m)), reactive oxygen species (ROS) and NADH or reduced glutathione
      (GSH) under aerobic conditions. DADS treatment decreased intracellular GSH and
      elevated intracellular ROS levels. Additionally, DADS induced a marked decrease
      of Deltapsi(m) and lowered respiration in cell suspensions and isolated
      mitochondria. In vitro kinetic experiments in cell-free extracts suggest that
      glutathione-S-transferase (GST) is one of the intracellular targets of DADS.
      Additional targets were also identified, including inhibition of a site or sites
      between complexes II-IV in the electron transport chain, as well as the
      mitochondrial ATP-synthase. The results indicate that DADS is an effective
      antifungal agent able to trigger cell death in Candida, most probably by
      eliciting oxidative stress as a consequence of thiol depletion and impaired
      mitochondrial function.

PMID- 17534842
TI  - A brief review of the past, present and future of wood preservation.
AB  - Wood products used in exterior applications must be protected against
      biodeterioration by decay fungi, insects such as termites, and other organisms.
      Traditionally, wood products for residential or industrial applications have been
      protected by treatment with chromated copper arsenate (CCA) or older inexpensive
      organic biocides, but environmental and disposal concerns and governmental
      regulations have resulted in a rapid and dramatic worldwide shift to copper-based
      systems. The current development trend is towards employing totally organic
      biocides based on relatively benign and expensive agrochemicals, with continuing
      research directed towards developing non-biocidal methods to protect wood.

PMID- 17534843
TI  - The phosphatidylserine receptor mediates phagocytosis by vascular smooth muscle
      cells.
AB  - Apoptosis participates in every step of atherogenesis, but the process of
      clearance of apoptotic cells by phagocytosis has been underestimated. Rapid
      removal of apoptotic cells is critical for tissue homeostasis, in order to avoid
      accumulation of necrotic material and subsequent inflammation in the pathological
      vascular wall. We have demonstrated by RT-PCR, western blot and
      immunocytofluorescence that vascular smooth muscle cells (VSMCs) express the
      phosphatidylserine receptor (PSR). We then tested the involvement of PSR in the
      ability of VSMCs to bind and engulf apoptotic cells. We used a model of senescent
      erythrocytes, which expose PS after 4 days of culture (85% of cells relative to
      8% in freshly isolated erythrocytes). The pseudo-peroxidase activity of
      haemoglobin contained within erythrocytes allowed us to quantify per se both
      binding and phagocytosis by VSMCs. We have also shown by light and confocal
      microscopy that VSMCs were able to ingest aged erythrocytes. Addition of a
      blocking antibody or transfection of VSMCs by a siRNA directed against PSR
      reduced the binding and engulfment of aged erythrocytes by more than 90%. These
      results suggest that PSR is involved in phagocytosis of PS-presenting cells.
      Incubation of aged erythrocytes with VSMCs also significantly increased the
      expression of PSR, suggesting that the tethering/ingestion of apoptotic cells
      triggers this process. Immunostaining for PSR in complicated atherosclerotic
      plaques shows positivity in the media and macrophage-rich areas. The mechanisms
      underlying phagocytosis and involving PSR in vivo, within the pathological
      arterial wall, deserve further investigation.

PMID- 17534844
TI  - Oncogenic role of JC virus in lung cancer.
AB  - The JC virus (JCV) infects a large proportion of the population world wide and
      can cause progressive multifocal leucoencephalopathy in the context of
      immunodeficiency. Recent reports provide evidence that it may also be oncogenic.
      Here, JCV was examined by targeting its T-antigen in lung carcinomas (n=103) and
      normal lung tissues (n=18) by nested-PCR followed by Southern blot, real-time
      PCR, immunohistochemistry, in situ hybridization and in situ PCR. Additionally,
      expression of Ki-67, caspase-3, beta-catenin, p53, and Rb was analysed by
      immunohistochemistry on tissue microarrays of lung carcinomas. Copy numbers of
      JCV were compared with clinicopathological features. Normal lung tissue was
      positive significantly less frequently, and contained a lower copy number of JCV
      than lung carcinomas (p<0.05), and copies were lower in lung adenocarcinomas than
      in squamous, small or large cell carcinomas (p<0.05). In situ PCR and
      immunolabelling revealed JCV positivity in the nuclei of lung carcinoma cells.
      The JCV copy number correlated closely with sex, and expression of Ki-67 and
      membrane beta-catenin (p<0.05), but not with age, tumour size, pleural invasion,
      lymph node metastasis, expression of caspase-3, cytoplasmic beta-catenin, p53 or
      Rb, prognosis, smoking or cancer family history (p>0.05). Age and UICC staging
      were independent prognostic factors for lung carcinoma patients. These data
      suggest that JCV may be involved in lung carcinogenesis, especially in tumour
      types other than adenocarcinoma. Lung carcinomas with higher JCV copy numbers
      display high proliferation and down-regulation of cell adhesion mediated by
      membrane beta-catenin.

PMID- 17534845
TI  - Interferon-gamma-dependent mechanisms of mycobacteria-induced pulmonary
      immunopathology: the role of angiostasis and CXCR3-targeted chemokines for
      granuloma necrosis.
AB  - The mechanisms leading to granuloma caseation, a hallmark of tuberculosis (TB) in
      humans, are poorly understood. Lung histopathology of C57BL/6 (WT) mice 16 weeks
      after aerosol infection with Mycobacterium avium strain TMC724 is uniquely
      characterized by centrally necrotizing granulomas, strongly resembling human TB
      lesions. However, IFN-gamma-deficient (GKO) and IFN-gamma-receptor-deficient
      (GRKO) mice did not develop granuloma necrosis following M. avium infection.
      Comparison of differentially expressed genes in infected WT and GKO lungs by DNA
      microarray and RNase protection assays revealed that the angiostatic chemokines
      CXCL9-11 were significantly reduced in GKO mice. In contrast, angiogenic
      mediators such as angiopoietin and vascular endothelial growth factor, and
      angiogenic chemokines such as CXCL2, CCL3, and CCL4, remained unchanged or were
      expressed at higher levels than in infected WT mice, suggesting impaired
      neovascularization of the granuloma as a possible mechanism for caseation in WT
      mice. Granuloma vascularization was significantly decreased in central, but not
      peripheral, areas of granulomas of infected WT compared to GKO mice. In contrast
      to GRKO mice, WT mice showed signs of severe hypoxia in cells immediately
      surrounding the necrotic core of granulomas as measured immunohistochemically
      with a reagent detecting pimonidazole adducts. To test the hypothesis that CXCR3,
      the common receptor for the angiostatic chemokines CXCL9-11, is involved in
      granuloma caseation, histomorphology was assessed in M. avium-infected mice
      deficient for CXCR3 (CXCR3-KO). 16 weeks after infection, these mice developed
      caseating granulomas similar to WT mice. We conclude that IFN-gamma causes a
      dysbalance between angiostatic and angiogenic mediators and a concomitant
      reduction in granuloma vascularization, but that CXCR3-targeted chemokines are
      not sufficient to induce granuloma necrosis in a mouse model of mycobacteria
      induced immunopathology.

PMID- 17534846
TI  - Disproportionate representation of KRAS gene mutation in atypical adenomatous
      hyperplasia, but even distribution of EGFR gene mutation from preinvasive to
      invasive adenocarcinomas.
AB  - In the resected lung, additional small lesions are occasionally found
      incidentally, and include the full spectrum of preinvasive to invasive lesions
      under the current putative schema of the sequential development of lung cancer.
      In this study, we examined EGFR and KRAS gene mutations in 119 synchronous
      pulmonary lesions, including 40 precursor lesions (atypical adenomatous
      hyperplasia, AAH), 26 carcinomas in situ (non-mucinous bronchioloalveolar
      carcinoma, BAC), 14 minimally invasive adenocarcinomas, 34 overt invasive
      adenocarcinomas, and five of other subtypes of cancer. Although the mutually
      exclusive nature of KRAS and EGFR gene mutations was maintained even in
      preinvasive lesions, the incidences of the lesions along the putative progression
      schema were quite different. The KRAS gene was mutated in 33% of AAH, 12% of
      carcinomas in situ, 8% of minimally invasive adenocarcinomas and 0% of well
      differentiated adenocarcinomas, whereas the frequencies of EGFR mutation did not
      fluctuate greatly, at 25%, 51%, 36%, 86% and 67%, respectively. These results are
      consistent with the findings of a published gene-targeted mouse model; the mice
      expressing oncogenic KRAS developed AAH but not invasive adenocarcinoma, whereas
      a spectrum of preinvasive to invasive adenocarcinomas was observed in the mice
      expressing mutant EGFR. Taking these factors together, it is suggested that AAH
      could develop by either KRAS or EGFR gene mutation, but AAH harbouring a KRAS
      gene mutation might not progress further to an invasive cancer.

PMID- 17534847
TI  - Genetic side effects accompanying gene targeting in yeast: the influence of short
      heterologous termini.
AB  - We investigated the influence of short terminal heterologies on recombination
      between transforming linear DNA fragments and the yeast Saccharomyces cerevisiae
      genome. The efficiency of plasmid integration to the CYC1 locus (ends-in assay)
      was decreased more than five-fold when the size of terminal heterology exceeded
      28 nucleotides (nt) and a similar inhibitory effect was also observed in the ends
      out assay (replacement of the ura3-52 allele by the URA3 gene). Plasmid
      integration occurred almost exclusively in the target homology and was
      accompanied by excessive degradation of the heterologous termini. Illegitimate
      integrations were much more frequent in the ends-out transformation in both the
      absence (8.9%) and the presence (23.7%) of 45/46 heterologous nucleotides at the
      ends of the transforming fragment. Interestingly, only about 60% of transformants
      arose by simple gene replacement, regardless of the presence of heterologous
      ends, whereas more complex interactions resulted in gene or whole chromosome
      duplications. Our results warn that different genetic alterations may be
      introduced in the host strain during ends-out transformation but also indicate
      possible mechanisms for formation of duplications in the genome.

PMID- 17534848
TI  - Bimolecular fluorescence complementation analysis system for in vivo detection of
      protein-protein interaction in Saccharomyces cerevisiae.
AB  - The bimolecular fluorescence complementation (BiFC) assay has been widely
      accepted for studying in vivo detection of protein-protein interactions in
      several organisms. To facilitate the application of the BiFC assay to yeast
      research, we have created a series of plasmids that allow single-step, PCR-based
      C- or N-terminal tagging of yeast proteins with yellow fluorescent protein
      fragments for BiFC assay. By examination of several interacting proteins (Sis1
      Sis1, Net1-Sir2, Cet1-Cet1 and Pho2-Pho4), we demonstrate that the BiFC assay can
      be used to reliably analyse the occurrence and subcellular localization of
      protein-protein interactions in living yeast cells. The sequences for the
      described plasmids were submitted to the GenBank under Accession Nos: EF210802,
      pFA6a-VN-His3MX6; EF210803, pFA6a-VC-His3MX6; EF210804, pFA6a-VN-TRP1; EF210807,
      pFA6a-VC-TRP1; EF210808, pFA6a-VN-kanMX6; EF210809, pFA6a-VC-kanMX6; EF210810,
      pFA6a-His3MX6-P(GAL1)-VN; EF210805, pFA6a-His3MX6-P(GAL1)-VC; EF210806, pFA6a
      TRP1-P(GAL1)-VN; EF210811, pFA6a-TRP1-P(GAL1)-VC; EF210812, pFA6a-kanMX6-P(GAL1)
      VN; EF210813, pFA6a-kanMX6-P(GAL1)-VC; EF521883, pFA6a-His3MX6-P(CET1)-VN;
      EF521884, pFA6a-His3MX6-P(CET1)-VC; EF521885, pFA6a-TRP1-P(CET1)-VN; EF521886,
      pFA6a-TRP1-P(CET1)-VC; EF521887, pFA6a-kanMX6-P(CET1)-VN; EF521888, pFA6a-kanMX6
      P(CET1)-VC.

PMID- 17534849
TI  - Nanofibers of fullerene C60 through interplay of ball-and-socket supermolecules.
AB  - Mixing solutions of p-tBu-calix[5]arene and C(60) in toluene results in a 1:1
      complex (C(60)) intersection(p-tBu-calix[5]arene), which precipitates as
      nanofibers. The principle structural unit is based on a host-guest ball-and
      socket nanostructure of the two components, with an extended structure comprising
      zigzag/helical arrays of fullerenes (powder X-ray diffraction data coupled with
      molecular modeling). Under argon at temperatures above 309 degrees C, the fibers
      undergo selective volatilization of the calixarenes to afford C(60)-core
      nanostructures encapsulated in a graphitic material sheath, which exhibits a
      dramatic increase in surface area. Above 650 degrees C the material exhibits an
      ohmic conductance response, due to the encapsulation process.

PMID- 17534850
TI  - Coadsorption-induced reconstruction of supramolecular assembly characteristics.
AB  - A host supramolecular structure consisting of bis-(2,2':6',2"-terpyridine)-4'
      oxyhexadecane (BT-O-C16) is shown to respond to coadsorbed molecules in dramatic
      ways, as observed by scanning tunneling microscopy (STM) on a highly oriented
      pyrolytic graphite (HOPG) surface under ambient conditions. Interestingly, the
      lattice parameter of the triphenylene-filled complex differs significantly from
      that of the coronene-filled one, although the triphenylene and coronene molecules
      are nearly the same size. The STM study and density functional theory
      calculations reveal that intermolecular hydrogen-bond interactions play an
      essential role in forming the assembly structures. The different electronic
      properties of coronene and triphenylene molecules are responsible for the
      difference in lattice parameters and consequently for the difference in filling
      behaviors in the coronene/BT-O-C16 and triphenylene/BT-O-C16 binary systems.

PMID- 17534851
TI  - Continuous monitoring of long-term outcomes with application to hip prostheses.
AB  - The CUSUM continuous monitoring method could be a valuable tool in evaluating the
      performance (revision experience) of prostheses used in hip replacement surgery.
      The dilemma when applying the CUSUM in this context is the choice of statistical
      model for the outcome (revision). The Bernoulli model is perhaps the most
      straightforward approach but the Poisson model is a plausible, and could be
      argued, preferable alternative for long-term outcomes such as this, provided the
      rate of revision with time from surgery can be assumed to be constant. However, a
      rate (or hazard) varying according to the Weibull distribution appears to be a
      better representation of a prosthesis lifetime. We show how to adapt the Poisson
      approach to allow for the hazard to vary according to the Weibull model as well
      as other parametric survival models. Application to data on a known poorly
      performing prosthesis shows both the Poisson and Weibull CUSUMs could have given
      early warning of the poor performance, with the Weibull chart alerting before the
      Poisson. Simulation work to investigate the robustness of the Poisson and Weibull
      CUSUM to departures from the underlying survival model highlights the need for
      correct specification of the model for the outcome.

PMID- 17534852
TI  - Quantitation and metabolism of mitoquinone, a mitochondria-targeted antioxidant,
      in rat by liquid chromatography/tandem mass spectrometry.
AB  - Mitoquinone (MitoQ10 mesylate) is a mitochondria-targeted antioxidant undergoing
      development for the treatment of neurodegenerative diseases. The aim of this
      study was to develop and validate an assay based on liquid chromatography/tandem
      mass spectrometry (LC/MS/MS) to determine mitoquinone and to detect and identify
      the metabolites of MitoQ10 in rat plasma after an oral dose. After a simple
      protein precipitation step, plasma samples were analyzed by reversed-phase liquid
      chromatography using gradient elution with acetonitrile/water/formic acid.
      Electrospray ionization in the positive ion mode with multiple reaction
      monitoring (MRM) was used to analyze mitoquinone employing the deuterated
      compound (d3-MitoQ10 mesylate) as internal standard. The calibration curve for
      mitoquinone was linear over the concentration range 0.5-250 ng/mL with a
      correlation coefficient>0.995. The method was sensitive (limit of quantitation
      0.5 ng/mL) and had acceptable accuracy (relative error<8.7%) and precision (intra
      and inter-day coefficient of variation<12.4%). Recoveries of mitoquinone at
      concentrations of 1.5, 20 and 200 ng/mL were in the range 87-114%. The method was
      successfully applied to a pharmacokinetic study in rat after a single oral dose
      in which four metabolites of MitoQ10 were tentatively identified as hydroxylated
      MitoQ10, desmethyl MitoQ10 and the glucuronide and sulfate conjugates of the
      quinol form of MitoQ10.

PMID- 17534853
TI  - Identification of palmatine and its metabolites in rat urine by liquid
      chromatography/tandem mass spectrometry.
AB  - Palmatine is an isoquinoline alkaloid that has been widely used in China for the
      treatment of various inflammatory diseases such as gynecological inflammation,
      bacillary dysentery, enteritis, respiratory tract infection, urinary infection,
      etc. In the study reported in this paper, a simple and rapid high-performance
      liquid chromatography/electrospray ionization (ESI) tandem mass spectrometric
      method (MS/MS) was developed for elucidation of the structures of metabolites of
      palmatine in rat urine after administration of a single dose (20 mg/kg). The rat
      urine samples were collected and purified through C18 solid-phase extraction
      cartridges, and then injected onto a reversed-phase C18 column with 60:40 (v/v)
      methanol/0.01% triethylamine solution (2 mM, adjusted to pH 3.5 with formic acid)
      as mobile phase and detected by on-line MS/MS. Identification of the metabolites
      and elucidation of their structures were performed by comparing changes in
      molecular masses (DeltaM), retention times and spectral patterns of product ions
      with those of the parent drug. As a result, six phase I metabolites, the parent
      drug palmatine and two phase II metabolites were identified in rat urine for the
      first time.

PMID- 17534854
TI  - A systematic study of carboxylic acids in negative ion mode electrospray
      ionisation mass spectrometry providing a structural model for ion suppression.
AB  - We report a systematic investigation of the effects and structural requirements
      for ion suppression in negative ion mode electrospray ionisation mass
      spectrometry of a series of carboxylic acids and present a structural model
      rationalising ion suppression effects.

PMID- 17534855
TI  - PREDICT-1 (CNA106030): the first powered, prospective trial of pharmacogenetic
      screening to reduce drug adverse events.
AB  - Pharmacogenetics (PGx) - the study of DNA variation in the human genome and the
      way this impacts the efficacy and safety of medicines - is becoming an
      increasingly important research tool as physicians, patients, regulatory
      authorities and payers look for innovative ways to improve the risk:benefit ratio
      of medicines. While scientific knowledge about PGx is rapidly increasing,
      implementation of PGx findings to patient care has yet to be fully achieved. One
      area where significant progress has been made is in the identification of PGx
      markers associated with variable response to antiretroviral medicines. For
      example, the major histocompatibility complex HLA-B*5701 allele has been
      associated with hypersensitivity to abacavir (ABC) by several independent
      researchers. While PGx associations have been identified largely through
      retrospective examination, the clinical utility of these PGx markers in patient
      care has not been prospectively determined in a randomized study. This paper
      outlines the design of a study to evaluate the utility of prospective screening
      for HLA-B*5701 to reduce the incidence of ABC hypersensitivity in an ABC-naive
      population of HIV-infected subjects. This represents the first fully powered,
      randomized, blinded, prospective study to determine the clinical utility of PGx
      screening to reduce drug-associated adverse events in any patient population.
      This type of trial design may have utility for other important medicines which
      have treatment-limiting side effects.

PMID- 17534856
TI  - Determining enediol compounds in tea using surface-assisted laser
      desorption/ionization mass spectrometry with titanium dioxide nanoparticle
      matrices.
AB  - We describe the use of titanium dioxide nanoparticles (TiO2 NPs) as selective
      probes and matrices for the determination of catechins using surface-assisted
      laser desorption/ionization mass spectrometry (SALDI-MS). The interactions
      between the enediol compounds and TiO2 NPs were evident by the change in color of
      the TiO2 NP solution from milky white to orange. Through these interactions, the
      TiO2 NPs could be used to concentrate enediol compounds, including catechins and
      ascorbic acid. The limits of detection (LODs) for three catechins--catechin, (-)
      epigallocatechin, and (-)-epigallocatechin gallate--at a signal-to-noise ratio of
      3 were 0.45, 1.85 and 0.65 microM, respectively. The TiO2 NP matrices provide a
      number of advantages over conventional organic matrices (e.g. 2',4',6'
      trihydroxyacetophenone), including ease of sample preparation, less background
      noise in the low-mass region, and high repeatability. The applicability of this
      method was confirmed through the high reproducibility of the determination of the
      two catechins in tea samples that had not been subjected to any sample
      preparation procedures (shot-to-shot variation: <10%).

PMID- 17534857
TI  - An electrospray ionisation tandem mass spectrometric investigation of selected
      psychoactive pharmaceuticals and its application in drug and metabolite profiling
      by liquid chromatography/electrospray ionisation tandem mass spectrometry.
AB  - A tandem mass spectrometric investigation of the collision-induced dissociation
      of five commonly prescribed psychoactive pharmaceuticals, risperidone,
      sertraline, paroxetine, trimipramine, and mirtazapine, and their metabolites has
      been carried out. Quadrupole ion trap mass spectrometry was employed to generate
      tandem mass spectrometric (MS/MS) data of the compounds under investigation and
      structural assignments of product ions were supported by quadrupole time-of
      flight mass spectrometry. These fragmentation studies were then utilised in the
      development of a liquid chromatographic method to identify the drugs and their
      metabolites in human hair and saliva samples, thus providing relevant profiling
      information.

PMID- 17534858
TI  - Laser desorption/ionization techniques in the characterization of high-molecular
      weight oil fractions--Part 2: De-asphalted oils.
AB  - The composition of the de-asphalted oil fraction obtained from two different
      Italian fields was studied by laser desorption/ionization mass spectrometry.
      These fractions were treated with different solvent mixtures, and subfractions
      containing saturates, aromatic and polar compounds were obtained and analyzed by
      the same instrumental approach.The investigation showed clear differences between
      the samples coming from the two oils. The instrumental approach did not lead to
      an accurate description of the different components in terms of elemental
      composition and structures; however, valid information could be obtained on the
      molecular weight distribution of the components of the different fractions.

PMID- 17534859
TI  - A metabonomic study of strain- and age-related differences in the Zucker rat.
AB  - Ultra-performance liquid chromatography (UPLC) coupled to orthogonal acceleration
      time-of-flight mass spectrometry (oa-TOFMS) in positive electrospray ionization
      mode was used to obtain metabolite profiles for urine obtained from three strains
      of Zucker rat. These were the Zucker lean, the Zucker (fa/fa) obese and the
      Zucker lean/(fa) cross. Clear age- and strain-related differences were noted with
      the leptin-deficient (fa/fa) obese animal showing significant differences from
      both the other Zucker rat strains with respect to metabolite profiles.

PMID- 17534860
TI  - Analysis of erlotinib and its metabolites in rat tissue sections by MALDI
      quadrupole time-of-flight mass spectrometry.
AB  - A qualitative and quantitative analysis of erlotinib (RO0508231) and its
      metabolites was carried out on rat tissue sections from liver, spleen and muscle.
      Following oral administration at a dose of 5 mg/kg, samples were analyzed by
      matrix-assisted laser desorption ionization (MALDI) with mass spectrometry (MS)
      using an orthogonal quadrupole time-of-flight instrument. The parent compound was
      detected in all tissues analyzed. The metabolites following drug O-dealkylation
      could also be detected in liver sections. Sinapinic acid (SA) matrix combined
      with the dried-droplet method resulted in better conditions for our analysis on
      tissues. Drug quantitation was investigated by the standard addition method and
      liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis on the tissue
      extracts. The presence of the parent compound and of its O-demethylated
      metabolites was confirmed in all tissue types and their absolute amounts
      calculated. In liver the intact drug was found to be 3.76 ng/mg tissue, while in
      spleen and muscle 6- and 30-fold lower values, respectively, were estimated.
      These results were compared with drug quantitation obtained by whole-body
      autoradiography, which was found to be similar. The potential for direct
      quantitation on tissue sections in the presence of an internal standard was also
      investigated using MALDI-MS. The use of alpha-cyano-4-hydroxycinnamic acid (CHCA)
      as the matrix resulted in better linearity for the calibration curves obtained
      with reference solutions of the drug when compared to SA, but on tissue samples
      no reliable quantitative analysis was possible owing to the large variability in
      the signal response. MS imaging experiments using MALDI in MS/MS mode allowed
      visualizing the distribution of the parent compound in liver and spleen tissues.
      By calculating the ratio between the total ion intensities of MS images for liver
      and spleen sections, a value of 6 : 1 was found, which is in good agreement with
      the quantitative data obtained by LC-MS/MS analysis.

PMID- 17534861
TI  - Determination of the cation-chelating potential of C-methylthiolated beta-lactams
      and their sulfones by electrospray ionization mass spectrometry.
AB  - The chelation potential of highly lipophilic C-dimethylthiolated monocyclic beta
      lactams was examined using electrospray ionization mass spectrometry (ESI-MS).
      The metal salts NaCl, KCl, CaCl2, ZnCl2, Cu(NO3)2, CdSO4, MnCl2, and Mg(NO3)2
      were used for the analysis. The K+ adducts of the compounds studied were more
      responsive in ESI analysis, compared to their Na+ adducts, regardless of the
      oxidation state of the sulfur (in the methylthio or the sulfone groups) and the
      type of the group adjacent to the lactam carbonyl. Opening of the beta-lactam
      ring, leading to formation of a chargeable N-atom, had little to no effect on the
      K+ adduct formation. Interactions of the methylthio group with the divalent zinc
      ion were also observed.

PMID- 17534862
TI  - Metabolic footprinting as a tool for discriminating between brewing yeasts.
AB  - The characterization of industrial yeast strains by examining their metabolic
      footprints (exometabolomes) was investigated and compared to genome-based
      discriminatory methods. A group of nine industrial brewing yeasts was studied by
      comparing their metabolic footprints, genetic fingerprints and comparative
      genomic hybridization profiles. Metabolic footprinting was carried out by both
      direct injection mass spectrometry (DIMS) and gas chromatography time-of-flight
      mass spectrometry (GC-TOF-MS), with data analysed by principal components
      analysis (PCA) and canonical variates analysis (CVA). The genomic profiles of the
      nine yeasts were compared by PCR-restriction fragment length polymorphism (PCR
      RFLP) analysis, genetic fingerprinting using amplified fragment length
      polymorphism (AFLP) analysis and microarray comparative genome hybridizations
      (CGH). Metabolomic and genomic analysis comparison of the nine brewing yeasts
      identified metabolomics as a powerful tool in separating genotypically and
      phenotypically similar strains. For some strains discrimination not achieved
      genomically was observed metabolomically.

PMID- 17534863
TI  - Antigen presentation and transfer between B cells and macrophages.
AB  - B cells play an active role in directing immunity against specific proteins in
      part because of their capacity to sequester antigen via B cell receptor (BCR).
      Our prior findings indicate that B cells can initiate an immune response in vivo
      to self proteins independent of other antigen-presenting cells (APC). However,
      these studies also demonstrated that both dendritic cells and macrophages are
      important in the ongoing immune response. The present work illustrates a
      mechanism by which antigen acquired by B cells through BCR is specifically
      transferred to other APC, in particular, macrophages. The transfer of antigen is
      dependent on the specificity of BCR and requires direct contact between the
      cells, but does not require MHC compatibility between the cells and is
      independent of the activation state of macrophages. Antigen transfer is
      functional, in that macrophages, which received B cell derived-antigen, can
      activate CD4 T cells. Overall, these results define a novel mechanism by which B
      cells can focus immunity toward a specific antigen and transfer the ability to
      activate CD4 T cells to other APC.

PMID- 17534864
TI  - Pathways utilized by dendritic cells for binding, uptake, processing and
      presentation of antigens derived from HIV-1.
AB  - The outcome following HIV infection depends on the nature and durability of the
      HIV-specific T cell response induced initially. The activation of protective T
      cell responses depends upon dendritic cells (DC), antigen-presenting cells which
      have the capacity to process and present viral antigens. DC pulsed with
      aldrithiol-2-inactivated HIV and delivered in vivo were reported to induce immune
      responses and promote virologic control in chronically HIV-1-infected subjects.
      To gain an understanding of this phenomenon, we characterized the steps involved
      in the presentation of antigens derived from aldrithiol-2-treated vs. infectious
      HIV-1 by DC. Antigen presentation, on both MHC class I and II, was independent of
      DC-specific ICAM-3-grabbing integrin, DEC-205 and macrophage mannose receptor, C
      type lectins expressed by the DC. Inhibitor studies showed that presentation on
      MHC class I was dependent on viral fusion in a CD4/coreceptor-dependent manner,
      both at the cell surface and within endosomes, and access to the classical
      endosomal processing pathway. MHC class II presentation of HIV-associated
      antigens was dependent on active endocytosis, probably receptor-mediated, and
      subsequent degradation of virions in acidified endosomes in the DC. Our study
      brings forth new facts regarding the binding, uptake, and processing of
      chemically inactivated virions leading to efficient antigen presentation and
      should aid in the design of more effective HIV vaccines.

PMID- 17534865
TI  - The importance of expectations on the recovery period after cancer treatment.
AB  - The purpose was to study expectations concerning recovery-related changes in
      life, e.g. beliefs regarding future adjustment back to 'normal' life after
      curative cancer treatment, whether these expectations were met and their
      importance for both patients' and their spouses' quality of life and
      psychological distress. Sixty-two patients and 42 spouses took part in the study.
      Data on recovery-related expectations, measured using a study-specific
      questionnaire (RRE), on quality of life using EORTC-QLQ C-30 and on psychological
      distress using HADS, were collected directly after completion of treatment, four
      and 16 months later. Optimism was measured using LOT at the last follow-up. The
      results demonstrate that patients generally had higher recovery-related
      expectations than did their spouses, and their expectations were also fulfilled
      to a lesser degree at both follow-ups. However, the expectations, or whether
      these were met, were generally not associated with their quality of life or
      psychological distress. The few associations that were made indicated that
      fulfilled expectations meant higher quality of life and/or less distress. The
      participants' optimism was associated with both their quality of life and
      psychological distress. It is concluded that optimism influenced the
      participants' quality of life and psychological distress to a higher degree than
      did their recovery-related expectations.

PMID- 17534866
TI  - Concordance between patients' desired and actual decision-making roles in breast
      cancer care.
AB  - This study explored breast cancer patients' preferences and experiences for
      participation in treatment decision making as well as the concordance between
      patients' actual and desired decision making. The interplay between depression,
      anxiety and decision-making preferences was also examined.A consecutive sample of
      primary breast cancer patients was recruited within a week of either surgery or
      the beginning of neo-adjuvant chemotherapy in two breast cancer centres in
      Germany. Women were asked to complete a self-explanatory questionnaire. Most
      patients (40.2%) of the 137 participants preferred the physician to make the
      treatment decision. A total of 63.4% were able to fulfil their preferred decision
      making role. Breast cancer patients who wanted the physician to make the decision
      and patients who wanted to make the decision on their own were more likely to
      have their preferences met than patients who wished to share the decision (p <
      0.01). Availability of treatment choice and the level of depression influenced
      the preferred decision-making preference. Limited concordance between desired and
      actual decision making of patients with collaborative decision-making preferences
      suggests the need for better communication and physician training on shared
      decision making.

PMID- 17534867
TI  - Genetic characterization of commercial Saccharomyces cerevisiae isolates
      recovered from vineyard environments.
AB  - One hundred isolates of the commercial Saccharomyces cerevisiae strain Zymaflore
      VL1 were recovered from spontaneous fermentations carried out with grapes
      collected from vineyards located close to wineries in the Vinho Verde wine region
      of Portugal. Isolates were differentiated based on their mitochondrial DNA
      restriction patterns and the evaluation of genetic polymorphisms was carried out
      by microsatellite analysis, interdelta sequence typing and pulsed-field gel
      electrophoresis (PFGE). Genetic patterns were compared to those obtained for 30
      isolates of the original commercialized Zymaflore VL1 strain. Among the 100
      recovered isolates we found a high percentage of chromosomal size variations,
      most evident for the smaller chromosomes III and VI. Complete loss of
      heterozygosity was observed for two isolates that had also lost chromosomal
      heteromorphism; their growth and fermentative capacity in a synthetic must medium
      was also affected. A considerably higher number of variant patterns for
      interdelta sequence amplifications was obtained for grape-derived strains
      compared to the original VL1 isolates. Our data show that the long-term presence
      of strain VL1 in natural grapevine environments induced genetic changes that can
      be detected using different fingerprinting methods. The observed genetic changes
      may reflect adaptive mechanisms to changed environmental conditions that yeast
      cells encounter during their existence in nature.

PMID- 17534869
TI  - Chiral recognition of the Schiff bases by NMR spectroscopy in the presence of a
      chiral dirhodium complex. Deuterium isotope effect on 13C chemical shift of the
      optically active Schiff bases and their dirhodium adducts.
AB  - The dirhodium method has been successfully applied in chiral recognition of the
      optically active Schiff bases, derivatives of ortho-hydroxyaldehydes existing in
      the NH-form. or at tautomeric equilibrium. The position of the equilibrium of
      Schiff bases as well as their adducts has been established on the basis of
      measurements of deuterium isotope effects on 13C chemical shifts. The presence of
      the proton transfer equilibrium or NH-tautomer has promoted the adduct formation.
      At the equilibrium state, formation of the adducts has shifted the proton
      transfer equilibrium towards the NH-form. The binding site was the oxygen atom of
      the proton donor group.

PMID- 17534868
TI  - Sibling stem cell donor experiences at a single institution.
AB  - Allogeneic bone marrow (BM) and cytokine mobilized peripheral blood stem cell
      (PBSC) transplantation can be curative for patients with malignant and
      nonmalignant hematologic diseases. Siblings are most often selected as a donor
      match; however, research on sibling donors is limited and has focused primarily
      on conventional BM donors. This exploratory study describes the experiences of
      PBSC sibling donors at a single institution. Through retrospective interviews, 14
      sibling donors shared their perceived needs and concerns before and after their
      stem cell collection. Donors identified fears about the donation procedure, and
      expressed the need for more information about transplant outcome and
      complications. The inclusion of the sibling donors themselves, rather than the
      report of their parents or health-care providers and the qualitative nature of
      the structured design allowed sibling donors to describe their concerns and
      thoughts without being restrained by the beliefs of the participant's parents,
      researcher or sibling's medical team. Suggestions for visual educational tools,
      psychosocial interventions and future research are provided.

PMID- 17534870
TI  - Janocchio--a Java applet for viewing 3D structures and calculating NMR couplings
      and NOEs.
AB  - We present a Java applet, based on the open source Jmol program, which allows the
      calculation of coupling constants and NOEs from a three-dimensional structure.
      The program has all the viewing features of Jmol, but adds the capability to
      calculate both H-H and H-C 3-bond couplings constants. In the case of H--H
      couplings, the Altona equation is used to perform this. The program also
      calculates NOEs using the full relaxation matrix approach. All these calculations
      are driven from a simple point and click interface. The program can calculate
      values for multi-structure files, and can produce input files for the
      conformational fitting program NAMFIS.

PMID- 17534872
TI  - Normal carbon acid referencing for protein amide hydrogen exchange.
AB  - Measurement of the exchange kinetics for amide hydrogens along the protein
      backbone continues to offer valuable insights into structural stability and
      conformational dynamics. Since such studies routinely compare samples that differ
      in solution conditions or mechanical handling, normalization of the relative
      exchange rates can present a potentially significant source of experimental
      uncertainty. The carbon acids 1,3-dimethylimidazolium cation and
      thiomethylacetonitrile exhibit base catalyzed exchange rates similar to those of
      the slowly exchanging amides, under conditions typical for protein studies. With
      13C enrichment at the acidic carbon position to facilitate selective observation,
      such carbon acids offer practical internal calibration of exchange.

PMID- 17534873
TI  - Homonuclear long-range correlation spectra from HMBC experiments by covariance
      processing.
AB  - We present a new application of covariance nuclear magnetic resonance processing
      based on 1H--13C-HMBC experiments which provides an effective way for
      establishing indirect 1H--1H and 13C--13C nuclear spin connectivity at natural
      isotope abundance. The method, which identifies correlated spin networks in terms
      of covariance between one-dimensional traces from a single decoupled HMBC
      experiment, derives 13C--13C as well as 1H--1H spin connectivity maps from the
      two-dimensional frequency domain heteronuclear long-range correlation data
      matrix. The potential and limitations of this novel covariance NMR application
      are demonstrated on two compounds: eugenyl-beta-D-glucopyranoside and an emodin
      derivative.

PMID- 17534874
TI  - Experimental and theoretical investigation of NMR 2JHH coupling constant on six
      membered ring systems containing oxygen or sulfur atoms.
AB  - Theoretical and experimental 2JHH coupling constants for six-membered rings
      containing oxygen or sulfur atoms were studied to investigate whether the 2JHH
      coupling constant can be used for stereoelectronic studies in heterocyclohexanes,
      instead of 1JCH, because it is well known that experimental measurements of 2JHH
      coupling constants at low temperature are much easier to determine than the
      corresponding 1JCH couplings. For all compounds studied here, the 2JHH coupling
      constants are affected by sigma*C-H antibonding occupancy together with bond
      angle effects. For cyclohexane and oxygen-containing compounds, the influence on
      the geminal coupling for Hax-C2-Heq and for X1-C2-X3 (X=O and C), bond angles are
      more pronounced than for the sulfur derivatives.

PMID- 17534876
TI  - 1H and 13C NMR assignments for two new angular furanocoumarin glycosides from
      Peucedanum praeruptorum.
AB  - Two novel angular-type furanocoumarin glycosides, peucedanoside A (1) and
      peucedanoside B (2), along with a known compound apterin (3), were isolated from
      the roots of Peucedanum praeruptorum Dunn. Their chemical structures were
      determined by MS, NMR spectroscopy and chemical analysis. Complete assignments of
      the 1H and 13C NMR spectroscopic data were achieved by 1D and 2D NMR experiments
      including DEPT, HSQC, HMBC and ROESY.

PMID- 17534875
TI  - Associations of ABCB1, ABCC2, and ABCG2 polymorphisms with irinotecan
      pharmacokinetics and clinical outcome in patients with advanced non-small cell
      lung cancer.
AB  - BACKGROUND: The authors investigated whether ABCB1, ABCC2, and ABCG2 genetic
      polymorphisms affect pharmacokinetics (PK) of irinotecan and treatment outcome of
      patients with advanced nonsmall cell lung cancer (NSCLC). METHODS: Blood samples
      from 107 NSCLC patients treated with irinotecan and cisplatin chemotherapy were
      used for genotyping ABCB1 (1236C > T, 2677G > T/A, 3435C > T), ABCC2 (-24C > T,
      1249G > A, 3972C > T), and ABCG2 (34G > A, 421C > A) polymorphisms. Genotypes
      were correlated with irinotecan-PK, toxicity, tumor response, and survival.
      RESULTS: Among 8 polymorphisms, 3435TT and 2677TT were associated with AUC(SN
      38G) and CL(SN-38G). When haplotypes are assigned, 2677TT/3435TT carriers showed
      significantly lower AUC(SN-38G) (P = .006), whereas 2677GG/3435CC carriers showed
      significantly higher AUC(SN-38) (P = .039). These findings suggest that 2677TT
      and 3435TT variants are associated with higher efflux activity. In toxicity, the
      2677G/T or A was associated with grade 4 neutropenia. The 2677GG carriers showed
      significantly lower absolute neutrophil count during the 1(st) cycle (P = .012)
      as well as entire course of chemotherapy (P = .042). The 3435TT was associated
      with higher frequency of grade 3 diarrhea (P = .047). In tumor response, ABCC2 
      24TT and 3972TT genotypes were associated with higher response rates (P = .031
      and P = .048, [corrected] respectively) and longer progression-free survival (P =
      .010 and P = .019, [corrected] respectively), which was sustained in haplotype
      analysis. CONCLUSIONS: Specific polymorphisms of ABCB1 and ABCC2 can influence
      disposition and tumor response to irinotecan by regulating transporter activity.
      These findings may help to individualize irinotecan-based chemotherapy in
      patients with advanced NSCLC.

PMID- 17534877
TI  - Solid-state 17O NMR study of the electric-field-gradient and chemical shielding
      tensors in polycrystalline amino acids.
AB  - We have presented a systematic experimental investigation of carboxyl oxygen
      electric-field-gradient (EFG) and chemical shielding (CS) tensors in crystalline
      amino acids. Three 17O-enriched amino acids were prepared: L-aspartic acid, L
      threonine, and L-tyrosine. Analysis of two-dimensional 17O multiple-quantum magic
      angle spinning (MQMAS), MAS, and stationary NMR spectra yields the 17O CS, EFG
      tensors and the relative orientations between the two tensors for the amino
      acids. The values of quadrupolar coupling constants (CQ) are found to be in the
      range of 6.70-7.60 MHz. The values of deltaiso lie in the range of 268-292 ppm,
      while those of the delta11 and delta22 components vary from 428 to 502 ppm, and
      from 303 to 338 ppm, respectively. There is a significant correlation between the
      magnitudes of delta22 components and C--O bond lengths. Since C--O bond length
      may be related to hydrogen-bonding environments, solid-state 17O NMR has
      significant potential to provide insights into important aspects of hydrogen
      bonds in biological systems.

PMID- 17534878
TI  - Experimental and DFT studies on the transmission mechanisms of analogous NMR JCH
      and JCC couplings in 1-X- and 1-X-3-methylbicyclo[1.1.1]-pentanes.
AB  - The main aim of this work is to compare the transmission mechanisms for the Fermi
      contact term of spin-spin couplings, SSCCs, in series 1-X-bicyclo[1.1.1]-pentane,
      (1), and 1-X-3-methylbicyclo[1.1.1]pentane, (2), and from that comparison to gain
      insight into some subtle aspects of the FC transmission. To this end, 18 members
      of the latter series were isotopically enriched in (13)C at the methyl position
      and the following couplings were measured; 1JC3CMe, 3JC1CMe and 4JCXCMe. These
      three types of SSCCs in (2) are compared, respectively, with 1JC3H3, 3JC1H3 and
      4JCXH in (1); these latter values were taken from previous works. Since electron
      delocalization plays an important role in the transmission of the FC interaction,
      the natural bond orbital (NBO) method is employed to quantify electron
      delocalization interactions within selected members of series (1) and (2). It is
      found that 1JC3H3 SSCCs in (1) is more efficiently transmitted than 1JC3CMe SSCCs
      in (2). On the other hand, 3JC1H3 and 4JCXH SSCCs in (1) are notably less
      efficiently transmitted than 3JC1CMe and 4JCXCMe SSCCs in (2), although
      substituent effects on these two SSCCs show the opposite trends. These different
      efficiencies are rationalized in terms of different sigma-hyperconjugative
      interactions in both series of compounds.

PMID- 17534879
TI  - Guttiferic acid, a novel rearrangement product from minor chromenoxanthone
      pigments of Garcinia morella Desr.
AB  - Morellic and isomorellic acids (2 and 3), present in the seed coat as well as
      resinous exudate of Garcinia morella Desr., are geometric isomers and
      structurally related to morellin (1), the major chromenoxanthone pigment. Both
      form crystalline complexes with pyridine and afford guttiferic acid (7), a novel
      skeletal rearrangement product, when heated with mild alkali. Structure of the
      latter has been deduced mainly by a comparative study of 1H and 13C NMR spectra
      of methyl morellate (5), methyl-O-methyl morellate (6), guttiferic acid (7) and
      dimethyl guttiferate (8).

PMID- 17534880
TI  - Explaining inconsistent results in cancer quality of life studies: the role of
      the stress-response system.
AB  - This study tests the hypothesis that avoidance and intrusion play different roles
      in health-related quality of life (QoL) in women who have undergone breast cancer
      surgery. We assessed QoL (RAND-36), avoidance, intrusion, and total cancer
      related distress (Impact of Event Scale) in 83 women at 3, 6, 9, and 12 months
      after mastectomy. Social functioning and role limitations improved over time;
      physical functioning, general health, and mental health did not change; vitality
      initially improved followed by a decrease to a below initial level; physical pain
      initially improved followed by a decrease to an above initial level. Cancer
      related distress remained high during follow-up. Individual variation in QoL as
      assessed across the four measurement times was associated with individual
      variation in intrusion but not with individual variation in avoidance. Baseline
      intrusion did not predict the subsequent course of QoL but high initial avoidance
      was associated with an unfavourable time course in physical functioning, social
      functioning, and general health. Hence, variation in intrusion over time explains
      variation in QoL while baseline avoidance predicts the subsequent course of QoL.
      The findings provide new insight into the relationship between the stress
      response system in QoL and women with breast cancer.

PMID- 17534881
TI  - Companion participation in cancer consultations.
AB  - OBJECTIVE: Companions play an important role in cancer care. This investigation
      compared the communication of unaccompanied patients, accompanied patients, and
      companions during lung cancer consultations. Factors affecting the active
      participation of companions were analyzed. METHODS: Participants included
      unaccompanied patients (N=48), accompanied patients (N=84), and companions (N=84)
      of newly diagnosed lung cancer patients seen at a large southern VA medical
      center. The consultations were audiotaped, then transcribed. Coded utterances
      included patients' and companions' active participation (asking questions,
      expressing concerns, and making assertions) and physicians' use of facilitative
      communication. Mixed linear regression was used for comparisons of accompanied
      patients' participation to that of their companions and to determine the
      independent predictors of companion participation and patient satisfaction.
      RESULTS: The combined companion plus patient participation did not differ from
      the participation of unaccompanied patients. Patterns of companion participation
      varied greatly as almost half the interactions had a relatively passive companion
      (contributed to less than 40% of the patient plus companion active participation)
      but 33% of the consultations had an active companion and passive patient.
      Companions with less active participation accompanied black patients and received
      proportionally less facilitative communication from physicians. Patient
      satisfaction was lower when companion and patient had similar levels of
      participation. CONCLUSION: Companions vary greatly in their participation in lung
      cancer visits. Physicians facilitate companion participation through the use of
      partnership-building and supportive communication. The companions of black
      patients were less active than their white counterparts which parallels other
      research indicating that black patients are often less active than white
      patients. Such communicative discrepancies could contribute to racial disparities
      in cancer care.

PMID- 17534882
TI  - Husbands' perceptions of wives' adjustment to breast cancer: the impact on wives'
      mood.
AB  - Married women's adjustment to breast cancer is positively influenced by their
      husbands' emotional support and by both spouses' active coping strategies.
      However, little is known about how women's adjustment is related to their
      husbands' perceptions of their psychosocial impairment. The current study
      examined the relationships among wives' coping strategies, the extent of
      congruence between wives' and husbands' perceptions of wives' adjustment, and
      wives' mood disturbance in 45 women with Stage I or II breast cancer and their
      husbands. Mediational analyses demonstrated that discrepancies between husbands'
      perceptions of wives' adjustment and wives' perceptions of their own adjustment
      mediated the relationship between wives' use of avoidant coping strategies and
      wives' mood disturbance. The findings suggest that husbands' over- or under
      estimation of wives' adjustment may have a negative impact on wives' mood.
      Implications for future research are discussed.

PMID- 17534883
TI  - Assessment of solvent effects: do weak alignment media affect the structure of
      the solute?
AB  - Alignment media used for measuring residual dipolar couplings, such as solutions
      of filamentous phages, phospholipid mixtures, polyacrylamide gels and various
      lyotropic liquid crystalline systems were investigated with respect to solvent
      effects on molecular structure. Structural parameters of the small rigid model
      compound 13C-acetonitrile were calculated from dipolar couplings and variations
      from expectation values were used for assessment of solvent effects. Only minor
      solvent effects were observed for most of the media employed and the measured
      structural data are in good agreement with microwave data and theoretical
      predictions.

PMID- 17534884
TI  - Optimising reaction performance in the pharmaceutical industry by monitoring with
      NMR.
AB  - Quality assurance and process understanding are assuming increasing importance in
      the production of Active Pharmaceutical Ingredients (APIs). NMR has the potential
      to report on physical processes, quantities, structures, and speciation as
      chemical reactions progress. Following the progression of chemical reactions by
      placing the sample in an NMR tube, one can perform a large number of useful
      studies that provide chemical and mechanistic insight. But this simple approach
      can have limitations, and we have therefore constructed an apparatus comprising a
      laboratory reactor coupled with an NMR flow cell. The reactor duplicates the
      exact reaction conditions that will apply with large-scale production. This
      reaction mixture is sampled and pumped to a high-resolution NMR flow cell where
      the spectrum is recorded through the course of the reaction. We demonstrate the
      utility of reaction monitoring using NMR both for simple cases where tubes can be
      used, and describe the design of the on-flow apparatus and highlight its utility
      with an example.

PMID- 17534885
TI  - NMR spectra, GIAO and charge density calculations of five-membered aromatic
      heterocycles.
AB  - The B3LYP/6-31+G(d) molecular geometry optimized structures of 17 five-membered
      heterocycles were employed together with the gauge including atomic orbitals
      (GIAO) density functional theory (DFT) method at the B3LYP/6-31+G(d,p), B3LYP/6
      311++G(d,p) and B3LYP/6-311+G(2d,p) levels of theory for the calculation of
      proton and carbon chemicals shifts and coupling constants. The method of geometry
      optimization for pyrrole (1), N-methylpyrrole (2) and thiophene (7) using the
      larger 6-311++G(d,p) basis sets at the B3LYP/6-31+G(d,p), B3LYP/6-311++G(d,p),
      B3LYP/6-31+G(2d,p) and B3LYP/cc-pVTZ levels of theory gave little difference
      between calculated and experimental values of coupling constants. In general, the
      (1)H and 13C chemical shifts for all compounds are in good agreement with
      theoretical calculations using the smaller 6-31 basis set. The values of
      nJHH(n=3, 4, 5) and rmnJ(CH)(n=1, 2, 3, 4) were predicted well using the larger 6
      31+G(d,p) and 6-311++G(d,p) basis sets and at the B3LYP/6-31+G(d,p), B3LYP/6
      311++G(d,p), B3LYP/6-31+G(2d,2p) levels of theory. The computed atomic charges
      [Mulliken; Natural Bond Orbital Analysis (NBO); Merz-Kollman (MK); CHELP and
      CHELPG] for the B3LYP/6-311++G(d,p) geometry optimized structures of 1-17 were
      used to explore correlations with the experimental proton and carbon chemical
      shifts.

PMID- 17534886
TI  - Mechanism of naked DNA clearance after intravenous injection.
AB  - BACKGROUND: Injection of naked DNA has been viewed as a safer alternative to
      current gene delivery systems; however, the rate of clearance from the
      circulation has been a constant barrier in developing these methods. Naked DNA
      after intravenous (i.v.) injection will be taken up by the liver and depredated
      by serum nucleases. MATERIALS AND METHODS: Our study examines the mechanisms
      involved in clearance of naked DNA by each compartment, the blood and the liver,
      in an in vivo mouse model. Confocal microscopy and transmission electron
      microscopy were employed to identify the type of cells taking up DNA and the
      barrier to DNA access to hepatocytes, respectively. RESULTS: Our data showed the
      liver could take up over 50% of 5 microg perfused pDNA, with a maximum 25 microg
      of pDNA during a single pass, and a slower clearance rate compared to that of
      liver uptake. It was demonstrated that naked DNA is primarily taken up by the
      liver endothelial cells and this endothelial barrier to transfection could be
      overcome by manually massaging the liver, which enlarges the fenestrae.
      CONCLUSIONS: This study clarifies the mechanism by which naked DNA is eliminated
      from the circulation after i.v. injection, focusing on the role of both the liver
      and blood compartments in vivo (i.e. mouse). With this knowledge, we can more
      clearly understand the mechanism of naked DNA clearance and develop more
      efficient strategies for DNA transfer in vivo.

PMID- 17534887
TI  - Optimization of short-term transgene expression by sodium butyrate and ubiquitous
      chromatin opening elements (UCOEs).
AB  - BACKGROUND: Predictable and adequate transgene expression is essential for
      clinical gene therapy. Several studies have focused on optimization of transgene
      expression. In this study the effect of sodium butyrate (NaB) and a ubiquitous
      chromatin opening element (UCOE) on short-term gene expression after adenovirus
      mediated gene transfer in fibroblastic interface cells from periprosthetic tissue
      in loosened orthopedic implants is investigated. METHODS: Cultures of diploid
      human interface cells from four patients were infected with an adenovirus type-5
      vector that carries the luciferase gene driven by the cytomegalovirus (CMV)
      promoter as a reporter. In addition, viruses with a UCOE were evaluated. Twenty
      four hours after infection NaB was added in concentrations of 0 to 9 mM.
      Luciferase activity was tested after a further 24 h. RESULTS: NaB in a
      concentration of 6 mM caused a 7- to 16-fold increase in reporter gene expression
      compared to control condition. There was no difference in reporter gene
      expression when cells were infected with Ad.1.5UCOE-CMV.Luc compared to
      Ad.CMV.Luc. A combination of NaB and a UCOE had no advantage over NaB alone.
      CONCLUSIONS: Addition of NaB results in a marked increase in transgene expression
      in cultured cells. This would allow the enhancement of the expression of the
      transgene, without requiring a higher vector dose. Butyrate administration could
      not be substituted by inclusion of UCOEs in the vector. It remains to be
      established whether the effective concentrations of butyrate can be obtained in
      vivo.

PMID- 17534888
TI  - Methylthioadenosine phosphorylase (MTAP) in hearing: gene disruption by
      chromosomal rearrangement in a hearing impaired individual and model organism
      analysis.
AB  - Genes with a role in the auditory system have been mapped by genetic linkage
      analysis of families with heritable deafness and then cloned through positional
      candidate gene approaches. Another positional method for gene discovery is to
      ascertain deaf individuals with balanced chromosomal translocations and identify
      disrupted or disregulated genes at the site(s) of rearrangement. We report herein
      the use of fluorescence in situ hybridization (FISH) to map the breakpoint
      regions on each derivative chromosome of a de novo apparently balanced
      translocation, t(8;9)(q12.1;p21.3)dn, in a deaf individual. Chromosomal
      breakpoints were assigned initially by GTG-banding of metaphase chromosomes and
      then BAC probes chosen to map precisely the breakpoints by FISH experiments. To
      facilitate cloning of the breakpoint sequences, further refinement of the
      breakpoints was performed by FISH experiments using PCR products and by Southern
      blot analysis. The chromosome 9 breakpoint disrupts methylthioadenosine
      phosphorylase (MTAP); no known or predicted genes are present at the chromosome 8
      breakpoint. Disruption of MTAP is hypothesized to lead to deafness due to the
      role of MTAP in metabolizing an inhibitor of polyamine synthesis. Drosophila
      deficient for the MTAP ortholog, CG4,802, were created and their hearing
      assessed; no hearing loss phenotype was observed. A knockout mouse model for MTAP
      deficiency was also created and no significant hearing loss was detected in
      heterozygotes for Mtap. Homozygous Mtap-deficient mice were embryonic lethal.

PMID- 17534889
TI  - Epigenetic silencing of CDX2 is a feature of squamous esophageal cancer.
AB  - CDX2, a mammalian homologue of the homeobox gene 'caudal,' is expressed in gut
      epithelia and plays an important role in establishing the intestinal phenotype
      during development. Mice heterozygously disrupted for CDX2 develop disorganized
      polypoid hamartomas with glandular epithelium and stratified squamous metaplasia
      resembling foregut mucosa. Since no genetic disruptions of CDX2 have been
      reported to explain loss of gene function, we examined whether epigenetic
      mechanisms altered CDX2 expression. Eleven of 17 squamous esophageal cancer cell
      lines lacked expression of CDX2 that was restored following treatment with 5-aza
      2'-deoxycytidine, while all colorectal cancer cell lines expressed CDX2. Loss of
      expression was associated with DNA methylation in the 5' region of CDX2
      determined by methylation specific PCR and bisulfite sequencing. Methylation of
      CDX2 was rare in primary colorectal (1 of 44 tumors, 2%) and esophageal
      adenocarcinoma neoplasms (2 of 43 tumors, 5%), but was common in esophageal
      squamous carcinoma (24 of 45 tumors, 49%). No CDX2 methylation was found in
      normal tissues. Using semi-quantitative RT-PCR, expression of CDX2 was found in
      low level in normal esophagus, at higher levels in primary adenocarcinoma of the
      esophagus, but not in primary squamous cancers of the esophagus. Restoration of
      CDX2 in silenced cell lines resulted in expression of the CDX2 target gene MUC2,
      a gene important in glandular differentiation. Our results suggest that the
      inactivation of CDX2 in esophageal cancer associated with DNA methylation may be
      an important determinant of the squamous or non-adenomatous phenotype.

PMID- 17534890
TI  - Unexpected paracrine action of prostate cancer cells harboring a new class of
      androgen receptor mutation--a new paradigm for cooperation among prostate tumor
      cells.
AB  - The emergence of mutations in the androgen receptor (AR) gene is a recurrent
      event during progression of prostate cancer (PCa) on androgen ablation therapy.
      In this study, we show that nonsense mutations that lead to carboxyl-terminal end
      truncated ARs are found at high frequency in metastatic PCas. Transcriptional
      activities of the Q640X mutant AR in the androgen-sensitive LNCaP cell line
      differ to those of the wild-type AR. Indeed, this mutant AR exhibits strong and
      ligand-independent transcriptional activities from an artificial promoter
      construct containing two repeats of androgen-responsive elements, but is inactive
      on the human PSA gene promoter. Nevertheless, the expression of the Q640X mutant
      AR in LNCaP cells is accompanied by an increase in the level of PSA protein, and
      by an increase in the expression of the endogenous AR gene. This enhanced
      expression of the endogenous AR gene is not limited to the sole transfected
      cells, but is observed in non-transfected neighboring cells. Additionally, in co
      cultures of transfected and non-transfected LNCaP cells, the Q640X mutant AR
      leads to an unpredicted nuclear localization of the endogenous AR protein in the
      two cellular populations and this, in the absence of androgen. These data
      indicate that cells expressing the Q640X mutant AR acquire the property to emit a
      signal that activates the AR in neighboring cells by a paracrine mechanism and in
      a ligand-independent manner. Our data strongly support the notion of cooperation
      among tumor cells in PCa and could be of relevance for the understanding of
      progression on androgen ablation therapy.

PMID- 17534891
TI  - Malignant ascites protect against TRAIL-induced apoptosis by activating the
      PI3K/Akt pathway in human ovarian carcinoma cells.
AB  - Ascites are commonly found in ovarian cancer patients with advanced disease and
      are rich in cellular components and growth-promoting factors. The purpose of this
      study was to assess the effect of malignant ascites on TRAIL-induced apoptosis.
      We demonstrate that malignant ascites obtained from women with advanced ovarian
      cancer protect tumor cells from TRAIL- and FasL-induced apoptosis but not against
      cisplatin-induced apoptosis. This antiapoptotic effect was consistently found
      among different malignant ascites while nonmalignant peritoneal fluids or
      conditioned medium from TRAIL-resistant cells failed to protect tumor cells
      against TRAIL killing. Malignant ascites strongly inhibits TRAIL-induced caspase
      3 activation and PARP cleavage. Furthermore, ascites activate PI3K and its
      downstream target Akt and increases c-FLIP(S) protein levels without affecting
      ERK phosphorylation status. The antiapoptotic effect of malignant ascites is
      abrogated by the inhibition of PI3K with LY294002, by a specific inhibitor of Akt
      and by Akt siRNA. We further show that the pro-survival effect of ascites can be
      suppressed by down-regulation of c-FLIP(S). Our data indicate that malignant
      effusions protect against TRAIL-induced apoptosis by activating the PI3K/Akt
      pathway. These findings demonstrate that the tumor microenvironment may
      contribute to the resistance of ovarian cancer cells to death receptor-induced
      apoptosis.

PMID- 17534892
TI  - Carbaryl exposure and incident cancer in the Agricultural Health Study.
AB  - Carbaryl is a carbamate insecticide with a broad spectrum of uses in
      agricultural, commercial and household settings. It has previously been linked
      with non-Hodgkin lymphoma (NHL) but studies of cancer risk in humans are limited.
      We examined occupational carbaryl use and risk of all cancers in the Agricultural
      Health Study, a prospective study of a cohort of pesticide applicators in North
      Carolina and Iowa. This analysis included 21,416 subjects (1,291 cases) enrolled
      from 1993-1997 and followed for cancer incidence through 2003. Pesticide exposure
      and other data were collected using self-administered questionnaires. Poisson
      regression was used to calculate rate ratios (RRs) and 95% confidence intervals
      (CIs) while controlling for potential confounders. Carbaryl was not associated
      with cancer risk overall. Relative to subjects who never used carbaryl, melanoma
      risk was elevated with >175 lifetime exposure-days (RR = 4.11; 95%CI, 1.33-12.75;
      p-trend = 0.07), >10 years of use (RR = 3.19; 95%CI, 1.28-7.92; p-trend = 0.04),
      or >or=10 days of use per year (RR = 5.50; 95%CI, 2.19-13.84; p-trend < 0.001).
      Risk remained after adjusting for sunlight exposure. Although not significant,
      there appeared to be a trend of decreasing prostate cancer risk with increasing
      level of exposure. A small increase in NHL risk was observed using some, but not
      all, exposure measures. No associations were observed with other examined cancer
      sites. Because the observed results were not hypothesized a priori and because of
      limited study of their biological plausibility, they should be interpreted with
      caution.

PMID- 17534893
TI  - Differential DNA methylation associated with hepatitis B virus infection in
      hepatocellular carcinoma.
AB  - Gene inactivation through DNA hypermethylation plays a pivotal role in
      carcinogenesis. This study aimed to profile aberrant DNA methylation in different
      stages of liver disease, namely noncirrhosis, cirrhosis and hepatocellular
      carcinoma (HCC), and also to clarify the influence of hepatitis B virus (HBV)
      infection on the aberrant DNA methylation in HCCs. Promoter methylation in
      p14(ARF), p16(INK4a), O(6)-methylguanine-DNA methyltransferase (MGMT),
      glutathione S-transferase pi (GSTP1) and E-cadherin (E-Cad) genes of 58 HCCs
      paired with adjacent nontumorous tissues was assayed by methylation-specific PCR.
      HBV infection was determined using a hepatitis B virus surface antigen (HBsAg)
      serological assay. The frequency of p16(INK4a) promoter methylation increased
      from noncirrhotic, cirrhotic, to HCC tissues (noncirrhotic vs. HCC, p < 0.001),
      while that of GSTP1 promoter methylation increased in cirrhotic tissues compared
      to noncirrhotic ones (p = 0.029). The frequency of GSTP1 promoter
      hypermethylation is significantly higher in HCC than in nontumorous tissues (p =
      0.022) from HBsAg-positive patients, but not the HBsAg-negative controls (p =
      0.289). While the frequency of E-Cad promoter hypermethylation remained high in
      both nontumorous tissues and HCCs from HBsAg-positive patients (p = 0.438), it
      was lower in HCCs than in nontumorous tissues from HBsAg-negative patients (p =
      0.002). In contrast, the frequency of p16(INK4a), MGMT and p14(ARF) promoter
      hypermethylation in HCCs was unrelated to HBsAg status. In conclusion, aberrant
      DNA methylation may begin at different stages of liver disease in a gene
      dependent manner. Moreover, HBV infection may enhance or maintain GSTP1 and E-Cad
      promoter methylation and thereby affect hepatocarcinogenesis.

PMID- 17534894
TI  - CD40-mediated death and cytokine secretion in colorectal cancer: a potential
      target for inflammatory tumour cell killing.
AB  - CD40, a member of the tumour necrosis factor family, is expressed in a variety of
      epithelial cells. Although soluble CD40 agonists are growth-inhibitory, membrane
      presented CD40 ligand (CD40L) induces extensive apoptosis in carcinoma cells.
      This study investigated whether CD40 is expressed in human colorectal carcinoma
      (CRC) cells and explored the functional consequences of CD40 ligation. CD40
      expression in a panel of CRC lines was assessed by flow cytometry and in resected
      human CRCs by immunohistochemistry. CRC cells were treated in vitro with soluble
      CD40 agonists or cocultured with fibroblasts expressing membrane-bound CD40
      ligand. Apoptosis was determined by flow cytometry using Annexin V/propidium
      iodide labelling and by a DNA fragmentation assay. Cytokine secretion induced by
      CD40 ligation was quantified by a multiplex-bead array approach. We show that
      CD40 is expressed in a proportion of established CRC lines in culture and that
      receptor expression is functional. Activation of CD40 by membrane-presented
      CD40L, but not soluble agonists, causes high levels of death in CD40-positive CRC
      cells and induces secretion of proinflammatory cytokines. In agreement with our
      in vitro observations, immunohistochemical studies demonstrated that CD40 is
      highly expressed in a proportion of colorectal cancer specimens. The high level
      of susceptibility of CRC cells to CD40-killing combined with the ability of CD40
      to induce concomitant secretion of proinflammatory cytokines suggest that CD40
      ligation may represent a novel mechanism for elimination of CRC cells and render
      CD40 a promising therapeutic target for the eradication of colorectal tumours.

PMID- 17534895
TI  - Inhibition of Wnt-2 and galectin-3 synergistically destabilizes beta-catenin and
      induces apoptosis in human colorectal cancer cells.
AB  - Constitutive activation of the Wnt pathway as a result of APC, AXIN1 or CTNNB1
      mutations has been found in most colorectal cancers. For a long time, this
      aberrant Wnt activation has been thought to be independent of upstream signals.
      However, recent studies indicate that upstream signals retain their ability to
      regulate the Wnt pathway even in the presence of downstream mutations. Wnt-2 is
      well known for its overexpression in colorectal cancer. Galectin-3 (Gal-3), a
      multifunctional carbohydrate binding protein implicated in a variety of
      biological functions, has recently been reported to interact with beta-catenin.
      In this study, we investigated roles of Wnt-2 and Gal-3 in the regulation of
      canonical Wnt/beta-catenin signaling. We found that siRNA silencing of either Wnt
      2 or Gal-3 expression inhibited TCF-reporter activity, decreased cytosolic beta
      catenin level and induced apoptosis in human colorectal cancer cells containing
      downstream mutations. More interestingly, we showed that inhibition of both Wnt-2
      and Gal-3 had synergistic effects on suppressing canonical Wnt signaling and
      inducing apoptosis, suggesting that aberrant canonical Wnt/beta-catenin signaling
      in colorectal cancer can be regulated at multiple levels. The combined inhibition
      of Wnt-2 and Gal-3 may be of superior therapeutic advantage to inhibition by
      either one of them, giving rise to a potential development of novel drugs for the
      targeted treatment of colorectal cancer.

PMID- 17534896
TI  - Adenovirus-mediated small hairpin RNA targeting Bcl-XL as therapy for colon
      cancer.
AB  - Bcl-XL, an anti-apoptotic protein of Bcl-2 family, is overexpressed in colon
      cancers. To determine Bcl-XL's potential feasibility as a therapeutic target, we
      constructed a recombinant adenovirus that expressed a U6 promoter-driven small
      hairpin RNA (shRNA) targeting Bcl-XL (Ad/Bcl-XL shRNA) and evaluated the vector's
      ability to induce RNA interference in vivo and alter apoptosis induction in colon
      cancer cells and tumours. Ad/Bcl-XL shRNA effectively knocked down Bcl-XL
      expression in colon cancer cells and decreased their viability. Treatment with
      Ad/Bcl-XL shRNA but not control vectors led to dramatically increased cleavage of
      cellular apoptosis-related enzymes caspase-9, caspase-3 and poly(ADP-ribose)
      polymerase. Ad/Bcl-XL shRNA also significantly suppressed the growth of
      subcutaneous tumours derived from DLD1 cells in a nude mouse model and did so
      without causing any obvious damage to normal tissues or normal human fibroblasts.
      Together, our results support the feasibility of using adenovirus-mediated RNA
      interference therapy targeting Bcl-XL against colon cancers and warrant further
      studies of its safety and efficacy.

PMID- 17534897
TI  - Alcohol and folate consumption and risk of benign proliferative epithelial
      disorders of the breast.
AB  - Alcohol consumption has been associated with increased breast cancer risk and the
      increase in risk may be attenuated by adequate folate intake. However, their
      associations with the risk of benign proliferative epithelial disorders (BPEDs)
      of the breast, possible precursors of breast cancer, are not well understood. To
      investigate these associations, we conducted a cohort study among 68,132
      postmenopausal women participating in the Women's Health Initiative randomized
      clinical trials. Women were prospectively followed and those reporting a breast
      procedure (open surgical biopsy or core needle biopsy) had histological sections
      obtained for central pathology review. A total of 1,792 women with BPED of the
      breast were identified over an average of 7.8 years of follow-up. Cox
      proportional hazards models were used to estimate hazard ratios (HRs) and 95%
      confidence limits (CLs) for the associations of interest. Compared to
      nondrinkers, total current alcohol intake of 30 g/day or more was not associated
      with BPED risk (HR = 0.98, 95% CL = 0.70, 1.38). The risk of BPED was not
      associated with folate intake from diet (highest vs. lowest quartile: HR = 1.10,
      95% CL = 0.96, 1.26), from supplements (yes vs. no: HR = 1.05, 95% CL = 0.96,
      1.16) or from all sources combined (highest vs. lowest quartile: HR = 1.11, 95%
      CL = 0.96, 1.27). Furthermore, there was no effect modification between alcohol
      and folate in relation to the risk of BPED. In conclusion, we observed that
      alcohol consumption and folate intake were not associated with altered risk of
      BPED, and that there was no effect modification between them in relation to the
      risk of BPED.

PMID- 17534898
TI  - Pancreatic cancer microenvironment.
AB  - Pancreatic ductal adenocarcinoma remains an extremely aggressive malignancy that
      is virtually therapy-resistant and has therefore one of the worst prognoses of
      all human cancers. The focus of research, which had been placed mostly on genetic
      and epigenetic alterations of the cancer cells themselves, has shifted gradually
      towards the microenvironment. The cancer microenvironment consists of various
      components, including fibroblasts, endothelial cells, immune cells, and endocrine
      cells, that interact with each other and the cancer cells in a complex fashion.
      This interplay has implications for pancreatic cancer cell growth, migration and
      invasion, angiogenesis, and immunological recognition of cancer cells. Evidence
      is accumulating that the cancer microenvironment plays an active role in disease
      progression, and efforts are being made to target this interplay between cancer
      cells and host cells to improve the outcome of this deadly disease.

PMID- 17534899
TI  - Neuronal protein synuclein gamma predicts poor clinical outcome in breast cancer.
AB  - Synuclein gamma (SNCG), previously identified as a breast cancer-specific gene
      (BCSG1), is highly expressed in breast carcinomas but not in normal epithelium.
      SNCG regulates many pathways in growth and progression of breast cancer. To
      determine if SNCG is a biomarker for clinical prognosis of breast cancer, we
      generated a panel of murine monoclonal antibodies (mAbs) against human SNCG and
      correlated SNCG protein expression in 358 clinical breast cancer specimens with
      clinical outcome. A panel of 14 mAbs was characterized by ELISA,
      immunoprecipitation (IP), Western blot, immunocytochemistry and
      immunohistochemistry. SNCG protein expression was determined in 438 clinical
      breast specimens by immunohistochemical analysis using mAb 5C5. Expression of
      SNCG was strongly correlated with the stage, lymph node involvement, metastasis,
      tumor size and Her-2 status, but its expression was not associated with ER and PR
      expression status. While 71.4% of advanced breast cancers were positive for SNCG
      expression, only 26.8% of Stage I/II breast cancers were positive for SNCG
      expression and 5.2% of benign hyperplasia expressed SNCG. SNCG protein was not
      detectable in normal tissue adjacent to breast cancer. After a median follow-up
      of 64 months, patients with an SNCG-positive tumor had a significantly shorter
      disease-free survival and overall survival and a high probability of death
      compared no expression of SNCG. Multivariate analysis demonstrated that SNCG was
      a strong independent prognostic variable. SNCG is a new unfavorable prognostic
      marker for breast cancer progression and a potential target for breast cancer
      treatment.

PMID- 17534900
TI  - Hyperglycemia in patients with acute myeloid leukemia is associated with
      increased hospital mortality.
AB  - BACKGROUND: Hyperglycemia is often observed in medically ill patients. Previous
      studies have shown that patients with hyperglycemia during induction therapy for
      acute lymphoblastic leukemia develop more infections and have shorter disease
      free survival. The authors hypothesized that hyperglycemia may be associated with
      adverse outcomes in patients with acute myeloid leukemia (AML) and sought to
      determine whether this association exists in this population. METHODS: The
      authors performed a retrospective cohort study to examine the relation between
      hyperglycemia and hospital mortality in patients with the diagnosis of AML. Two
      hundred eighty-three adult patients were treated over a 3-year period. All
      hospitalizations were reviewed during the study period, and glucose exposure and
      outcomes were quantified. RESULTS: Hyperglycemia during a patient's
      hospitalization was associated with increased hospital mortality (OR, 1.38; 95%
      CI, 1.23-1.55; P < .001) after adjusting for covariates, including disease state,
      treatment type, and response. The rise in mortality was evident at even mild
      levels (110-150 mg/dL) of glucose elevation. Although the odds of developing
      severe sepsis (OR, 1.24; 95% CI, 1.13.-1.38; P < .001) or severe sepsis with
      respiratory failure (OR, 2.04; 95% CI, 1.44-2.91; P < .001) were increased with
      hyperglycemia, sepsis did not appear to be the main factor responsible for the
      negative impact of hyperglycemia on hospital mortality. CONCLUSIONS: This study
      demonstrated an association between hospital mortality and even modest levels of
      hyperglycemia in AML patients. Prospective studies are needed to confirm this
      association and to discern causal pathways that mediate this effect.

PMID- 17534901
TI  - Fast decomposition of water and lipid using a GRASE technique with the IDEAL
      algorithm.
AB  - Three-point Dixon techniques achieve good lipid-water separation by estimating
      the phase due to field inhomogeneities. Recently it was demonstrated that the
      combination of an iterative algorithm (iterative decomposition of water and fat
      with echo asymmetry and least-squares estimation (IDEAL)) with a fast spin-echo
      (FSE) three-point Dixon method yielded robust lipid-water decomposition. As an
      alternative to FSE, the gradient- and spin-echo (GRASE) technique has been
      developed for efficient data collection. In this work we present a method for
      lipid-water separation by combining IDEAL with the GRASE technique. An approach
      to correct for errors in the lipid-water decomposition caused by phase
      distortions due to the switching of the readout gradient polarities inherent to
      GRASE is presented. The IDEAL-GRASE technique is demonstrated in phantoms and in
      vivo for various applications, including pelvic, musculoskeletal, and (breath
      hold) cardiac imaging.

PMID- 17534902
TI  - Statistical group comparison of diffusion tensors via multivariate hypothesis
      testing.
AB  - Diffusion tensor imaging (DTI) provides a powerful tool for identifying white
      matter (WM) alterations in clinical populations. The prevalent method for group
      level analysis of DTI is statistical comparison of the diffusion tensor
      fractional anisotropy (FA) metric. The FA metric, however, does not capture the
      full orientational information contained in the diffusion tensor. For example,
      the FA test is incapable of detecting group-level differences in diffusion
      orientation when the level of anisotropy is unaffected. Here, we apply
      multivariate hypothesis testing procedures to the elements of the diffusion
      tensor as an alternative to univariate testing using FA. Both parametric and
      nonparametric tests are proposed with each choice carrying specific assumptions
      about the diffusion tensor model. Of particular interest is the Cramer test,
      which works on Euclidean interpoint distances and can be readily adapted to a
      specific non-Euclidean framework by applying matrix logarithms to the diffusion
      tensors. Using Monte Carlo simulations, we show that multivariate tests can
      detect diffusion tensor principal eigenvector differences of 15 degrees with up
      to 80-90% power under typical design conditions. We also show that some
      multivariate tests are more sensitive to FA differences, when compared to a
      univariate test on FA, even if there is no principal eigenvector difference. The
      Cramer test, using the Euclidean interpoint distances, performed best under both
      simulation scenarios. When applying the Cramer test of the diffusion tensor in a
      clinical population with a history of migraine, a 169% increase was observed in
      the volume of a significant cluster compared to the univariate FA test.

PMID- 17534903
TI  - Undersampled radial MRI with multiple coils. Iterative image reconstruction using
      a total variation constraint.
AB  - The reconstruction of artifact-free images from radially encoded MRI acquisitions
      poses a difficult task for undersampled data sets, that is for a much lower
      number of spokes in k-space than data samples per spoke. Here, we developed an
      iterative reconstruction method for undersampled radial MRI which (i) is based on
      a nonlinear optimization, (ii) allows for the incorporation of prior knowledge
      with use of penalty functions, and (iii) deals with data from multiple coils. The
      procedure arises as a two-step mechanism which first estimates the coil profiles
      and then renders a final image that complies with the actual observations. Prior
      knowledge is introduced by penalizing edges in coil profiles and by a total
      variation constraint for the final image. The latter condition leads to an
      effective suppression of undersampling (streaking) artifacts and further adds a
      certain degree of denoising. Apart from simulations, experimental results for a
      radial spin-echo MRI sequence are presented for phantoms and human brain in vivo
      at 2.9 T using 24, 48, and 96 spokes with 256 data samples. In comparison to
      conventional reconstructions (regridding) the proposed method yielded visually
      improved image quality in all cases.

PMID- 17534904
TI  - Longitudinal gradient coil optimization in the presence of transient eddy
      currents.
AB  - The switching of magnetic field gradient coils in magnetic resonance imaging
      (MRI) inevitably induces transient eddy currents in conducting system components,
      such as the cryostat vessel. These secondary currents degrade the spatial and
      temporal performance of the gradient coils, and compensation methods are commonly
      employed to correct for these distortions. This theoretical study shows that by
      incorporating the eddy currents into the coil optimization process, it is
      possible to modify a gradient coil design so that the fields created by the coil
      and the eddy currents combine together to generate a spatially homogeneous
      gradient that follows the input pulse. Shielded and unshielded longitudinal
      gradient coils are used to exemplify this novel approach. To assist in the
      evaluation of transient eddy currents induced within a realistic cryostat vessel,
      a low-frequency finite-difference time-domain (FDTD) method using the total-field
      scattered-field (TFSF) scheme was performed. The simulations demonstrate the
      effectiveness of the proposed method for optimizing longitudinal gradient fields
      while taking into account the spatial and temporal behavior of the eddy currents.

PMID- 17534905
TI  - Degenerate mode band-pass birdcage coil for accelerated parallel excitation.
AB  - An eight-rung, 3T degenerate birdcage coil (DBC) was constructed and evaluated
      for accelerated parallel excitation of the head with eight independent excitation
      channels. Two mode configurations were tested. In the first, each of the eight
      loops formed by the birdcage was individually excited, producing an excitation
      pattern similar to a loop coil array. In the second configuration a Butler matrix
      transformed this "loop coil" basis set into a basis set representing the
      orthogonal modes of the birdcage coil. In this case the rung currents vary
      sinusoidally around the coil and only four of the eight modes have significant
      excitation capability (the other four produce anticircularly polarized (ACP)
      fields). The lowest useful mode produces the familiar uniform B(1) field pattern,
      and the higher-order modes produce center magnitude nulls and azimuthal phase
      variations. The measured magnitude and phase excitation profiles of the
      individual modes were used to generate one-, four-, six-, and eightfold
      accelerated spatially tailored RF excitations with 2D and 3D k-space excitation
      trajectories. Transmit accelerations of up to six-fold were possible with
      acceptable levels of spatial artifact. The orthogonal basis set provided by the
      Butler matrix was found to be advantageous when an orthogonal subset of these
      modes was used to mitigate B(1) transmit inhomogeneities using parallel
      excitation.

PMID- 17534906
TI  - Quantitative determination of Gd-DTPA concentration in T1-weighted MR renography
      studies.
AB  - A method for calculating contrast agent concentration from MR signal intensity
      (SI) was developed and validated for T(1)-weighted MR renography (MRR) studies.
      This method is based on reference measurements of SI and relaxation time T(1) in
      a Gd-DTPA-doped water phantom. The same form of SI vs. T(1) dependence was
      observed in human tissues. Contrast concentrations calculated by the proposed
      method showed no bias between 0 and 1 mM, and agreed better with the reference
      values derived from direct T(1) measurements than the concentrations calculated
      using the relative signal method. Phantom-based conversion was used to determine
      the contrast concentrations in kidney tissues of nine patients who underwent
      dynamic Gd-DTPA-enhanced 3D MRR at 1.5T and (99m)Tc-DTPA radionuclide renography
      (RR). The concentrations of both contrast agents were found to be close in
      magnitude and showed similar uptake and washout behavior. As shown by Monte Carlo
      simulations, errors in concentration due to SI noise were below 10% for SNR = 20,
      while a 10% error in precontrast T(1) values resulted in a 12-17% error for
      concentrations between 0.1 and 1 mM. The proposed method is expected to be
      particularly useful for assessing regions with highly concentrated contrast.

PMID- 17534907
TI  - Human brain-structure resolved T(2) relaxation times of proton metabolites at 3
      Tesla.
AB  - The transverse relaxation times, T(2), of N-acetylaspartate (NAA), total choline
      (Cho), and creatine (Cr) obtained at 3T in several human brain regions of eight
      healthy volunteers are reported. They were obtained simultaneously in 320 voxels
      with three-dimensional (3D) proton MR spectroscopy ((1)H-MRS) at 1 cm(3) spatial
      resolution. A two-point protocol, optimized for the least error per given time by
      adjusting both the echo delay (TE(i)) and number of averages, N(i), at each
      point, was used. Eight healthy subjects (four males and four females, age = 26 +/
      2 years) underwent the hour-long procedure of four 15-min, 3D acquisitions
      (TE(1) = 35 ms, N(1) = 1; and TE(2) = 285 ms, N(2) = 3). The results reveal that
      across all subjects the NAA and Cr T(2)s in gray matter (GM) structures (226 +/-
      17 and 137 +/- 12 ms, respectively) were 13-17% shorter than the corresponding
      T(2)s in white matter (WM; 264 +/- 10 and 155 +/- 7 ms, respectively). The T(2)s
      of Cho did not differ between GM and WM (207 +/- 17 and 202 +/- 8, respectively).
      For the purpose of metabolic quantification, these values justify to within +/
      10% the previous use of one T(2) per metabolite for 1) the entire brain and 2)
      all subjects. These T(2) values (which to our knowledge were obtained for the
      first time at this field, spatial resolution, coverage, and precision) are
      essential for reliable absolute metabolic quantification.

PMID- 17534908
TI  - Whole-heart coronary vein imaging: a comparison between non-contrast-agent- and
      contrast-agent-enhanced visualization of the coronary venous system.
AB  - The feasibility of three-dimensional (3D) whole-heart imaging of the coronary
      venous (CV) system was investigated. The hypothesis that coronary magnetic
      resonance venography (CMRV) can be improved by using an intravascular contrast
      agent (CA) was tested. A simplified model of the contrast in T(2)-prepared steady
      state free precession (SSFP) imaging was applied to calculate optimal T(2)
      preparation durations for the various deoxygenation levels expected in venous
      blood. Non-contrast-agent (nCA)- and CA-enhanced images were compared for the
      delineation of the coronary sinus (CS) and its main tributaries. A quantitative
      analysis of the resulting contrast-to-noise ratio (CNR) and signal-to-noise ratio
      (SNR) in both approaches was performed. Precontrast visualization of the CV
      system was limited by the poor CNR between large portions of the venous blood and
      the surrounding tissue. Postcontrast, a significant increase in CNR between the
      venous blood and the myocardium (Myo) resulted in a clear delineation of the
      target vessels. The CNR improvement was 347% (P < 0.05) for the CS, 260% (P <
      0.01) for the mid cardiac vein (MCV), and 430% (P < 0.05) for the great cardiac
      vein (GCV). The improvement in SNR was on average 155%, but was not statistically
      significant for the CS and the MCV. The signal of the Myo could be significantly
      reduced to about 25% (P < 0.001).

PMID- 17534909
TI  - Prepolarized fast spin-echo pulse sequence for low-field MRI.
AB  - Clinical MRI systems use magnetic fields of at least 0.5T to take advantage of
      the increase in signal-to-noise ratio (SNR) with B(0). Low-field MRI apparatus is
      less expensive and offers the potential benefit of improved T(1) contrast between
      tissues. The poor inherent SNR at low field can be offset by incorporating
      prepolarizing field pulses with the MRI pulse sequence. The prepolarizing field
      does not need to be as homogeneous as the detection field, so it can be generated
      by a relatively inexpensive electromagnet. Prepolarizing hardware for a 0.01T MRI
      system was developed together with a prepolarized MRI pulse sequence that
      incorporates fast imaging techniques to reduce acquisition times by a factor of 5
      relative to standard methods. Comparison images of test objects show that most of
      the enhanced SNR is retained with the fast method. Low-field images of a human
      wrist acquired using the fast prepolarized method are also shown.

PMID- 17534910
TI  - Joint image reconstruction and sensitivity estimation in SENSE (JSENSE).
AB  - Parallel magnetic resonance imaging (pMRI) using multichannel receiver coils has
      emerged as an effective tool to reduce imaging time in various applications.
      However, the issue of accurate estimation of coil sensitivities has not been
      fully addressed, which limits the level of speed enhancement achievable with the
      technology. The self-calibrating (SC) technique for sensitivity extraction has
      been well accepted, especially for dynamic imaging, and complements the common
      calibration technique that uses a separate scan. However, the existing method to
      extract the sensitivity information from the SC data is not accurate enough when
      the number of data is small, and thus erroneous sensitivities affect the
      reconstruction quality when they are directly applied to the reconstruction
      equation. This paper considers this problem of error propagation in the
      sequential procedure of sensitivity estimation followed by image reconstruction
      in existing methods, such as sensitivity encoding (SENSE) and simultaneous
      acquisition of spatial harmonics (SMASH), and reformulates the image
      reconstruction problem as a joint estimation of the coil sensitivities and the
      desired image, which is solved by an iterative optimization algorithm. The
      proposed method was tested on various data sets. The results from a set of in
      vivo data are shown to demonstrate the effectiveness of the proposed method,
      especially when a rather large net acceleration factor is used.

PMID- 17534911
TI  - Satiety and test meal intake among women with binge eating disorder.
AB  - OBJECTIVE: The purpose of the study was to measure test meal consumption and the
      changes in hunger and fullness during a test meal in obese individuals with and
      without binge eating disorder (BED) and normal-weight controls. METHOD: Twelve
      women with BED, 12 obese control participants, and 12 normal-weight control
      participants participated in two single-item test meal sessions. In one session
      participants were instructed to "binge," and the other eat a normal meal.
      Participants made ratings of hunger and fullness on visual analog scales after
      every 75-g increment of food. RESULTS: In comparison to obese or normal-weight
      controls, patients with BED consumed significantly more food to reach a similar
      level of fullness or hunger. CONCLUSION: Individuals with BED consumed
      significantly more food and showed blunted changes in hunger and fullness during
      both the binge and nonbinge meals. These findings suggest that individuals with
      BED may have disturbances in satiety that in some ways resemble those described
      among individuals with bulimia nervosa.

PMID- 17534913
TI  - Array compression for MRI with large coil arrays.
AB  - Arrays with large numbers of independent coil elements are becoming increasingly
      available as they provide increased signal-to-noise ratios (SNRs) and improved
      parallel imaging performance. Processing of data from a large set of independent
      receive channels is, however, associated with an increased memory and
      computational load in reconstruction. This work addresses this problem by
      introducing coil array compression. The method allows one to reduce the number of
      datasets from independent channels by combining all or partial sets in the time
      domain prior to image reconstruction. It is demonstrated that array compression
      can be very effective depending on the size of the region of interest (ROI).
      Based on 2D in vivo data obtained with a 32-element phased-array coil in the
      heart, it is shown that the number of channels can be compressed to as few as
      four with only 0.3% SNR loss in an ROI encompassing the heart. With twofold
      parallel imaging, only a 2% loss in SNR occurred using the same compression
      factor.

PMID- 17534912
TI  - Functional MRI impulse response for BOLD and CBV contrast in rat somatosensory
      cortex.
AB  - The contrast mechanism in functional MRI (fMRI) results from several vascular
      processes with different time scales, thus establishing a finite temporal
      resolution to fMRI experiments. In this work we measured the blood oxygen level
      dependent (BOLD) and iron-oxide-derived cerebral blood volume (CBV) impulse
      response (IR) in a rat model of somatosensory brain activation at 11.7T. A binary
      m-sequence probe method was used to obtain high-sensitivity single-pixel
      estimates of the IR, from which two parameters-the full width at half maximum
      (FWHM) and the time to peak (TTP)-were determined as indices of the temporal
      resolution of the hemodynamic response (HDR). The results (N = 11) show that the
      CBV IR (N = 5, subset) is significantly narrower (FWHM = 1.37 +/- 0.11 s), and
      peaks earlier (TTP = 1.65 +/- 0.15 s) than the BOLD IR (N = 11, FWHM = 1.92 +/-
      0.22 s and TTP = 2.18 +/- 0.14 s, respectively). These findings indicate that
      neurovascular control mechanisms have a temporal resolution better than 1.5 s
      FWHM, and point to a substantial contribution to BOLD of the dispersive transit
      of oxygenated hemoglobin across the rat vasculature, bringing important
      implications for the ultimately attainable temporal resolution of fMRI.

PMID- 17534914
TI  - Passive catheter tracking during interventional MRI using hyperpolarized 13C.
AB  - Interventional procedures in MRI can be performed preclinically using active or
      passive catheter-tracking methods. A novel passive nonproton technique is
      suggested that uses a catheter filled with a hyperpolarized (13)C contrast agent.
      A prototype three-lumen catheter was built with two closed lumens containing a
      flowing hyperpolarized (13)C contrast agent. Entire-length (13)C catheter
      projection visualization could be performed in vivo with a catheter SNR of
      approximately 80, one dual projection frame per approximately 700 ms, and an in
      plane resolution of 2 x 2 mm(2) while traveling through the aorta of a pig. The
      traveling path of the (13)C catheter was visualized after back-projection
      catheter reconstruction and after image fusion with an anatomical offline proton
      road map. Catheter length visualization was aided by an oblique planar
      visualization mode. The high catheter signal demonstrated, together with the
      entire catheter length visualization and high surrounding soft-tissue contrast,
      warrants further development into a real-time technique.

PMID- 17534915
TI  - Performance of an automated segmentation algorithm for 3D MR renography.
AB  - The accuracy and precision of an automated graph-cuts (GC) segmentation technique
      for dynamic contrast-enhanced (DCE) 3D MR renography (MRR) was analyzed using 18
      simulated and 22 clinical datasets. For clinical data, the error was 7.2 +/- 6.1
      cm(3) for the cortex and 6.5 +/- 4.6 cm(3) for the medulla. The precision of
      segmentation was 7.1 +/- 4.2 cm(3) for the cortex and 7.2 +/- 2.4 cm(3) for the
      medulla. Compartmental modeling of kidney function in 22 kidneys yielded a renal
      plasma flow (RPF) error of 7.5% +/- 4.5% and single-kidney GFR error of 13.5% +/-
      8.8%. The precision was 9.7% +/- 6.4% for RPF and 14.8% +/- 11.9% for GFR. It
      took 21 min to segment one kidney using GC, compared to 2.5 hr for manual
      segmentation. The accuracy and precision in RPF and GFR appear acceptable for
      clinical use. With expedited image processing, DCE 3D MRR has the potential to
      expand our knowledge of renal function in individual kidneys and to help diagnose
      renal insufficiency in a safe and noninvasive manner.

PMID- 17534916
TI  - Detection of 17O-tagged phosphate by (31)P MRS: a method with potential for in
      vivo studies of phosphorus metabolism.
AB  - We present a method for MR detection of (17)O-labeled phosphate groups. The
      method employs the T(2) relaxivity effect of (17)O on (31)P nuclei to distinguish
      between (17)O-labeled and unlabeled phosphate groups, and uses spin-echo (SE)
      acquisitions with RF decoupling at the (17)O frequency to generate (31)P spectra
      that show only (17)O-labeled phosphate groups. The method provides an alternative
      to spin-labeling experiments, which are limited to the study of rapidly
      exchanging phosphate groups by the T(1) relaxation rates of phosphorus nuclei. We
      demonstrate separation of MR signals from labeled and unlabeled phosphate
      containing compounds, and characterization of the T(2) effect of (17)O on
      phosphate nuclei in (17)O-labeled phosphate groups. Previous (17)O and (18)O
      phosphate-labeled studies used mass spectrometry or high-resolution MR
      spectroscopy (MRS) to detect the presence of an isotopic label, which requires ex
      vivo sample preparation. In our method the detection of (17)O-labeled phosphate
      is manifested as a large change in (31)P T(2), and thus allows in vivo detection
      using simple MR methods. Thus this method may have potential for in vivo studies
      of bioenergetics and the metabolism of phosphate-containing compounds.

PMID- 17534917
TI  - In vitro comparison of the biological effects of three transfection methods for
      magnetically labeling mouse embryonic stem cells with ferumoxides.
AB  - In vivo MRI of stem cells (SCs) is an emerging application to evaluate the role
      of cell therapy in restoring the injured myocardium. The high spatial and
      temporal resolution combined with iron-oxide-based intracellular labeling
      techniques will provide a sensitive, noninvasive, dual imaging modality for both
      cells and myocardium. In order to facilitate this novel imaging approach, much
      effort has been directed towards developing efficient transfection methods. While
      techniques utilizing poly-L-lysine (PLL), protamine sulfate (PS), and
      electroporation (ELP) have been proposed, the fundamental biological effects of
      these methods on mouse embryonic SCs (mESC) have not been investigated
      systematically. In this study a longitudinal in vitro evaluation of cellular
      viability, apoptosis, proliferation, and cardiac differentiation of magnetically
      labeled mESC was conducted. No significant difference was seen in these
      biological parameters among the three transfection methods. However, cardiac
      differentiation was most attenuated by ELP, and iron uptake was most effective by
      PS.

PMID- 17534918
TI  - Single-scan acquisition of registered hyperpolarized (3)He ventilation and ADC
      images using a hybrid 2D gradient-echo sequence.
AB  - The pulse sequences for hyperpolarized (3)He lung MRI that have made the most
      clinical impact to date are 1) those that supply regional apparent diffusion
      coefficient (ADC) measurements, which provide insight into early emphysematous
      destruction of the alveoli in the lungs, and 2) high-resolution ventilation
      images that provide regional indicators of airway obstruction in obstructive
      airway disease, such as asthma, cystic fibrosis, and chronic obstructive
      pulmonary disease (COPD). In this work a hybrid 2D ADC-ventilation sequence was
      used with low flip angles to acquire both sets of data in the same breath-hold.
      The performance of the sequence was investigated in vivo in a healthy subject and
      a subject with mild emphysema, and compared with conventional 2D gradient-echo
      (GRE) (3)He ventilation and ADC imaging sequences. Acquisition of the ADC and
      ventilation images in one breath-hold provides ventilation images with equal or
      better SNR (approximately 20) and the same spatial resolution (3.75 mm x 3.3 mm
      in plane) with simultaneous accurate, high-resolution ADC images. The hybrid
      sequence offers a means of conserving gas by using two-thirds of the (3)He gas
      needed for separate ADC and ventilation exams, and saves the subject from having
      to perform an extra breath-hold. The data are inherently spatially and temporally
      registered, allowing quantitative cross-correlation between high-spatial
      resolution ADC and ventilation data.

PMID- 17534919
TI  - High-field actively detuneable transverse electromagnetic (TEM) coil with low
      bias voltage for high-power RF transmission.
AB  - The design and construction of a 4T (170 MHz) transverse electromagnetic (TEM)
      actively detuneable quadrature head coil is described. Conventional schemes for
      active detuning require high negative bias voltages (>300 V) to prevent leakage
      of RF pulses with amplitudes of 1-2 kW. To extend the power handling capacity and
      avoid the use of high DC bias voltages, we developed an alternate method of
      detuning the volume coil. In this method the PIN diodes in the detuning circuits
      are shorted when the RF volume coil is tuned, and negatively biased with -12 V
      when the coil is detuned. To preserve the high Q(U)/Q(L) ratio of the TEM coil,
      we modified the method of Nabetani and Watkins (Proceedings of the 13th Annual
      Meeting of ISMRM, Kyoto, Japan, 2004, abstract 1574) by utilizing a high
      impedance (approximately 200 Omega), lumped-element, quarter-wavelength
      transformer. A Q(U) of 500 was achieved for the detuneable TEM, such that
      incorporation of the detuning network had minimal effect (<1 dB) on the
      performance of the coil in vivo.

PMID- 17534920
TI  - 2H double quantum filtered (DQF) NMR spectroscopy of the nucleus pulposus tissues
      of the intervertebral disc.
AB  - Deuterium (2H) double-quantum filtered (DQF) NMR spectroscopy of nucleus pulposus
      (NP) tissues from human intervertebral discs is reported. The DQF spectral
      intensities, DQ build-up rates, and DQF-detected rotating-frame spin-lattice
      relaxation times are sensitive to the degree of hydration of the NP tissue, and
      display a monotonous correlation with age between 15 and 80 years. The
      implications of this work are that the changes in water dynamics as detected via
      DQF NMR spectroscopy may be used as a probe of tissue degeneration in NP,
      particularly in the early stages of degeneration to which most standard NMR
      methods are not sensitive.

PMID- 17534921
TI  - Self-calibration method for radial GRAPPA/k-t GRAPPA.
AB  - Generalized autocalibrating partially parallel acquisitions (GRAPPA), an
      important parallel imaging technique, can be easily applied to radial k-space
      data by segmenting the k-space. The previously reported radial GRAPPA method
      requires extra calibration data to determine the relative shift operators. In
      this work it is shown that pseudo-full k-space data can be generated from the
      partially acquired radial data by filtering in image space followed by inverse
      gridding. The relative shift operators can then be approximated from the pseudo
      full k-space data. The self-calibration method using pseudo-full k-space data can
      be applied in both k and k-t space. This technique avoids the prescans and hence
      improves the applicability of radial GRAPPA to image static tissue, and makes k-t
      GRAPPA applicable to radial trajectory. Experiments show that radial GRAPPA
      calibrated with pseudo-full calibration data generates results similar to radial
      GRAPPA calibrated with the true full k-space data for that image. If motion
      occurs during acquisition, self-calibrated radial GRAPPA protects structural
      information better than externally calibrated GRAPPA. However, radial GRAPPA
      calibrated with pseudo-full calibration data suffers from residual streaking
      artifacts when the reduction factor is high. Radial k-t GRAPPA calibrated with
      pseudo-full calibration data generates reduced errors compared to the sliding
      window method and temporal GRAPPA (TGRAPPA).

PMID- 17534922
TI  - In vivo differentiation of N-acetyl aspartyl glutamate from N-acetyl aspartate at
      3 Tesla.
AB  - A method is described that allows the in vivo differentiation of N-acetyl
      aspartate (NAA) from N-acetyl aspartyl glutamate (NAAG) by in vivo MR
      spectroscopy (MRS) at 3 Tesla (3T). The method, which is based on MEGA-point
      resolved spectroscopy (PRESS) editing, selectively targets the aspartyl spin
      system of one species while deliberately removing the other species from the
      spectrum. This allows quantitative measurements of NAA and NAAG without the need
      for fitting of unresolved peaks. White matter concentrations of NAA (6.7 +/- 0.3
      mM) and NAAG (2.2 +/- 0.3 mM) were measured in 10 healthy volunteers to
      demonstrate the method.

PMID- 17534923
TI  - Effects of formalin fixation and collagen cross-linking on T2 and magnetization
      transfer in bovine nasal cartilage.
AB  - Endogenous collagen cross-links influence cartilage biomechanical properties and
      resistance to degradation. Formalin fixation modifies collagen residues and forms
      new cross-links in a dose-dependent manner. We tested the hypothesis that
      magnetization transfer (MT) effects and T(2) depend on collagen cross-linking in
      cartilage. These parameters were measured in bovine nasal cartilage (BNC) prior
      to fixation, after 9 weeks of immersion in formalin solutions ranging in
      concentration from 0% to 10%, and after NaBH(3)CN reduction and washing. T(2)
      decreased by 59.4% +/- 1.1% upon fixation in 10% formalin, and was 32.2% +/- 5.2%
      shorter than initial values after washing. The apparent MT rate increased 25.9%
      +/- 3.7% and 52.8% +/- 7.1% over baseline under these conditions. Biochemical
      assays showed no significant differences in water, proteoglycan, natural cross
      link, or collagen content between the 0% and 10% formalin-treated samples, while
      amino acid analysis demonstrated losses in (hydroxy)lysine and tyrosine, and new
      peaks consistent with methylene cross-links in fixed samples only. We conclude
      that formalin fixation of cartilage results in significant decreases in T(2) and
      increases in MT parameters that persist after removal of unreacted formaldehyde.
      The collagen cross-links thus created are associated with large changes in MT and
      T(2), indicating that interpretation of T(2) and MT values in terms of cartilage
      macromolecular content must be made with caution.

PMID- 17534924
TI  - Temporally constrained reconstruction of dynamic cardiac perfusion MRI.
AB  - Dynamic contrast-enhanced (DCE) MRI is a powerful technique to probe an area of
      interest in the body. Here a temporally constrained reconstruction (TCR)
      technique that requires less k-space data over time to obtain good-quality
      reconstructed images is proposed. This approach can be used to improve the
      spatial or temporal resolution, or increase the coverage of the object of
      interest. The method jointly reconstructs the space-time data iteratively with a
      temporal constraint in order to resolve aliasing. The method was implemented and
      its feasibility tested on DCE myocardial perfusion data with little or no motion.
      The results obtained from sparse k-space data using the TCR method were compared
      with results obtained with a sliding-window (SW) method and from full data using
      the standard inverse Fourier transform (IFT) reconstruction. Acceleration factors
      of 5 (R = 5) were achieved without a significant loss in image quality. Mean
      improvements of 28 +/- 4% in the signal-to-noise ratio (SNR) and 14 +/- 4% in the
      contrast-to-noise ratio (CNR) were observed in the images reconstructed using the
      TCR method on sparse data (R = 5) compared to the standard IFT reconstructions
      from full data for the perfusion datasets. The method has the potential to
      improve dynamic myocardial perfusion imaging and also to reconstruct other sparse
      dynamic MR acquisitions.

PMID- 17534925
TI  - Fast method for 1D non-cartesian parallel imaging using GRAPPA.
AB  - MRI with non-Cartesian sampling schemes can offer inherent advantages. Radial
      acquisitions are known to be very robust, even in the case of vast undersampling.
      This is also true for 1D non-Cartesian MRI, in which the center of k-space is
      oversampled or at least sampled at the Nyquist rate. There are two main reasons
      for the more relaxed foldover artifact behavior: First, due to the oversampling
      of the center, high-energy foldover artifacts originating from the center of k
      space are avoided. Second, due to the non-equidistant sampling of k-space, the
      corresponding field of view (FOV) is no longer well defined. As a result,
      foldover artifacts are blurred over a broad range and appear less severe. The
      more relaxed foldover artifact behavior and the densely sampled central k-space
      make trajectories of this type an ideal complement to autocalibrated parallel MRI
      (pMRI) techniques, such as generalized autocalibrating partially parallel
      acquisitions (GRAPPA). Although pMRI can benefit from non-Cartesian trajectories,
      this combination has not yet entered routine clinical use. One of the main
      reasons for this is the need for long reconstruction times due to the complex
      calculations necessary for non-Cartesian pMRI. In this work it is shown that one
      can significantly reduce the complexity of the calculations by exploiting a few
      specific properties of k-space-based pMRI.

PMID- 17534926
TI  - Short data-acquisition times improve projection images of lung tissue.
AB  - MR images of laboratory rat lungs that resolve the thin membranes that separate
      lung lobes are presented. It appears that the capabilities of in vivo small
      animal pulmonary MRI may rival those of in vivo small-animal X-ray CT. Free
      induction decay (FID)-projection imaging was employed with particular attention
      to the choice of acquisition time. For a given nominal resolution, one obtains
      optimal point discrimination when the acquisition time T(acq) normalized by the
      signal decay time constant T(2)(*) is approximately 0.8-0.9, although a better
      signal-to-noise ratio (SNR) is obtained when this quotient is 1.6. Currently
      available equipment should be able to even exceed the results presented herein.

PMID- 17534927
TI  - XTC MRI: sensitivity improvement through parameter optimization.
AB  - Xenon polarization Transfer Contrast (XTC) MRI pulse sequences permit the gas
      exchange of hyperpolarized xenon-129 in the lung to be measured quantitatively.
      However, the pulse sequence parameter values employed in previously published
      work were determined empirically without considering the now-known gas exchange
      rates and the underlying lung physiology. By using a theoretical model for the
      consumption of magnetization during data acquisition, the noise intensity in the
      computed gas-phase depolarization maps was minimized as a function of the gas
      phase depolarization rate. With such optimization the theoretical model predicted
      an up to threefold improvement in precision. Experiments in rabbits demonstrated
      that for typical imaging parameter values the optimized XTC pulse sequence
      yielded a median noise intensity of only about 3% in the depolarization maps.
      Consequently, the reliable detection of variations in the average alveolar wall
      thickness of as little as 300 nm can be expected. This improvement in the
      precision of the XTC MRI technique should lead to a substantial increase in its
      sensitivity for detecting pathological changes in lung function.

PMID- 17534928
TI  - Prognostic significance of combined analysis of ZAP-70 and CD38 in chronic
      lymphocytic leukemia.
AB  - The clinical heterogeneity that characterizes chronic lymphocytic leukemia (CLL)
      poses critical questions concerning the identification of high risk patients.
      Unmutated IgV(H) genes, CD38 and ZAP-70 expression have emerged as the most
      useful tools in identifying aggressive CLL. The simultaneous expression of ZAP-70
      and CD38 in 157 patients with CLL has been evaluated. Fifty-seven patients (36%)
      were positive for ZAP-70 and 46 patients (29%) were positive for CD38. Both
      molecules were highly correlated and predictive of the clinical course of the
      disease. According to the simultaneous evaluation of ZAP-70 and CD38, patients
      were divided into three groups. In 81 patients (52%), there was a negative
      concordance of both molecules (ZAP-70(-)/CD38(-)); in 27 patients (17%) there was
      a positive concordance (ZAP-70(+)/CD38(+)); in 49 patients (31%) there was a
      discordant expression (ZAP-70(+)/CD38(-) and ZAP-70(-)/CD38(+)). A comparison of
      the clinical and laboratory data showed in ZAP-70(+)/CD38(+) patients a
      significantly higher bone marrow and peripheral blood lymphocytosis, lower
      hemoglobin levels, more advanced clinical stage, and higher number of unmutated
      IgV(H) status with respect to the other two groups. Furthermore, ZAP
      70(+)/CD38(+) patients displayed a much shorter treatment-free interval (median
      12 months vs 42 months in discordant patients and not reached in ZAP-70(-)CD38(-)
      patients). These results prove that the concomitant evaluation of ZAP-70 and CD38
      expression allows the separation of CLL patients in prognostic subgroups and
      suggest that their simultaneous assessment should become an integral component of
      the CLL diagnostic grid.

PMID- 17534929
TI  - Hypomethylation of PRAME is responsible for its aberrant overexpression in human
      malignancies.
AB  - The preferentially expressed antigen of melanoma (PRAME) is expressed at high
      levels in large fractions of human malignancies, e.g., acute myeloid leukemia.
      Therefore, PRAME is an important marker for diagnosis of various malignant
      diseases and a relevant parameter for monitoring minimal residual disease. It is
      supposed to be involved in tumorigenic processes. Because of these important
      aspects we investigated its transcriptional regulation in detail. Most relevant
      was a detailed DNA methylation analysis of the PRAME 5' region by genomic
      sequencing in correlation with PRAME expression in various human patient samples
      and cell lines. In combination with DNA-truncation/transfection experiments with
      respect to DNA methylation, we show that changes in the methylation pattern in
      defined parts of the regulatory regions of PRAME are sufficient for its
      upregulation in cells usually not expressing the gene.

PMID- 17534930
TI  - Fatal Loeffler's endocarditis due to hypereosinophilic syndrome.
AB  - Hypereosinophilic syndrome (HES) is a rare disorder that can manifest in various
      organ systems. We report the case of a 54-year-old woman with a remote history of
      seizure disorder who presented with early signs of right-sided heart failure.
      Laboratory studies showed significant eosinophilia (8 x 10(9) l(-1)). Computed
      tomography showed heterogeneity of the liver, mild ascites, moderate pleural
      effusion, multiple small pulmonary emboli, and a large right ventricular mass.
      Cardiac magnetic resonance imaging demonstrated that the right ventricular mass
      was due to thrombus and extensive endomyocardial fibrosis, consistent with
      Loeffler's endocarditis. Bone marrow biopsy showed marked eosinophilia but no
      abnormal myeloid maturation or a lymphoproliferative disorder; flow cytometry
      showed no clonality. Extensive infectious, immunologic, and toxicological studies
      were negative. Despite resolution of peripheral eosinophilia with medical
      management, including corticosteroids and cytotoxic agents, anticoagulation for
      pulmonary emboli and ventricular thrombus, and conventional treatment for heart
      failure, she developed worsening anasarca and died from ventricular fibrillation
      within 4 weeks of presentation. Autopsy confirmed the diagnosis. Loeffler's
      endocarditis, usually a late manifestation of HES, is characterized by fibrous
      thickening of the endocardium, leading to apical obliteration and restrictive
      cardiomyopathy, resulting in heart failure, thromboembolic events, or atrial
      fibrillation. HES is a potentially fatal disease with less than 50% reported 10
      year survival. This case presentation is unusual in its rapidly progressive
      course leading to sudden death.

PMID- 17534931
TI  - Conformational solution studies of the SDS micelle-bound 11-28 fragment of two
      Alzheimer's beta-amyloid variants (E22K and A21G) using CD, NMR, and MD
      techniques.
AB  - The beta-amyloid (Abeta) is the major peptide constituent of neuritic plaques in
      Alzheimer's disease (AD) and its aggregation is believed to play a central role
      in the pathogenesis of the disease. Naturally occurring mutations resulting in
      changes in the Abeta sequence (pos. 21-23) are associated with familial AD-like
      diseases with extensive cerebrovascular pathology. It was proved that the
      mutations alter the aggregation ability of Abeta and its neurotoxicity. Among
      five mutations at positions 21-23 there are two mutations with distinct clinical
      characteristics and potentially distinct pathogenic mechanism-the Italian (E22K)
      and the Flemish (A21G) mutations. In our studies we have examined the structures
      of the 11-28 fragment of the Italian and Flemish Abeta variants. The fragment was
      chosen because it has been shown to be the most important for amyloid fibril
      formation. The detailed structure of both variants Abeta(11-28) was determined
      using CD, 2D NMR, and molecular dynamics techniques under water-SDS micelle
      conditions. The NMR analysis revealed two distinct sets of proton resonances for
      the peptides. The studies of both peptides pointed out the existence of well
      defined alpha-helical conformation in the Italian mutant, whereas the Flemish was
      found to be unstructured with the possibility of a bent structure in the central
      part of the peptide.

PMID- 17534932
TI  - Speech-language and hearing complaints of children and adolescents with brain
      tumors.
AB  - Central nervous system (CNS) tumors generally leave sequelae that may compromise
      speech, language, swallowing, hearing, and voice functions. This report describes
      the incidence of speech-language and hearing complaints and disorders in children
      and adolescents with CNS tumor under treatment at one of the most important
      Brazilian reference center for pediatric cancer. One-hundred ninety patients were
      examined for speech-pathology screening and analysis: forty-two percent presented
      with complaints and symptoms. From the remaining patients, 68% presented clinical
      symptoms and 32% were actually free from any speech-language and hearing-related
      symptoms. The high incidence of complaints and symptoms indicate that these
      patients might benefit from specific rehabilitation interventions.

PMID- 17534933
TI  - Pemetrexed, a multitargeted antifolate drug, demonstrates lower efficacy in
      comparison to methotrexate against osteosarcoma cell lines.
AB  - The folate inhibitor methotrexate (MTX) is an important component of osteosarcoma
      (OS) treatment regimens. New generation multitargeted antifolates, such as
      pemetrexed (PMX), have shown promise in the treatment of various solid tumors. In
      this study, the in vitro efficacy of MTX and PMX was compared in OS cell lines.
      MTX demonstrated a superior cytotoxic effect in comparison to PMX in all tested
      cell lines. Apoptosis assays revealed that both MTX and PMX induce apoptosis but
      MTX demonstrated superior efficacy. These in vitro results suggest that PMX as a
      single agent may not demonstrate improved efficacy compared to MTX in OS
      patients.

PMID- 17534934
TI  - Development of bullwhip neurons in the embryonic chicken retina.
AB  - We have recently described large, unipolar neurons (named bullwhip cells) that
      regulate the proliferation of progenitors in the circumferential marginal zone
      (CMZ) of the postnatal chicken retina (Fischer et al. [2005] J. Neurosci.
      25:10157-10166; [2006] J. Comp. Neurol. 496:479-494). There are only about 240
      bullwhip cells in the entire retina, and these cells are easily identified by
      their unique morphology and immunoreactivity for glucagon, glucagon-like peptide
      1 (GLP1), and substance P. The purpose of this study was to elucidate the
      development of bullwhip cells in the embryonic chicken retina. By using
      bromodeoxyuridine birth dating, we found that the bullwhip cells are generated
      very early during retinal development, between E4 and E5. Glucagon peptide was
      first detected in bullwhip cells at about E10, whereas substance P was not
      detected in the bullwhip cells until E15. Although glucagon peptide is not
      present during early stages of retinal development, we detected mRNA for glucagon
      receptor beginning at E7 and mRNA for GLP1 receptor at E5 through E14.
      Morphological differentiation of the bullwhip cells begins at about E14 and is
      completed by E18. The bullwhip cells are greatly overproduced, and nearly 80% of
      these cells undergo apoptotic cell death during late stages of embryonic
      development. The bullwhip cells that survive are those that project an axon-like
      process directly toward the CMZ; the cells that project in an inappropriate
      direction fail to survive. We conclude that cells fated to become bullwhip
      neurons are generated long before they begin to differentiate and that their
      survival depends on the orientation of their primary neurite.

PMID- 17534935
TI  - Functional connections within the human inferior frontal gyrus.
AB  - The highly convoluted and cytoarchitectonically diverse inferior frontal gyrus
      (IFG) of humans is known to be critically involved in a wide range of complex
      operations including speech and language processing. The neural circuitry that
      underlies these operations is not fully understood. We hypothesized that this
      neural circuitry includes functional connections within and between the three
      major IFG subgyri: the pars orbitalis, pars triangularis, and pars opercularis.
      To test this hypothesis we employed electrical stimulation tract-tracing
      techniques in 10 human patients undergoing surgical treatment for intractable
      epilepsy. The approach involved delivering repeated bipolar electrical stimuli to
      one site on the IFG while recording the electrical response evoked by that
      stimulus from a 64-contact grid overlying more distant IFG sites. In all
      subjects, stimulation of a site on one subgyrus evoked polyphasic potentials at
      distant sites, either on the same subgyrus or on an adjacent subgyrus. This
      provided prima facie evidence for a functional connection between the site of
      stimulation and the sites of the evoked response. The averaged evoked potentials
      tended to aggregate as response fields. The spatial spread of a response field
      indicated a divergent projection from the site of stimulation. When two or more
      sites were stimulated, the resulting evoked potentials exhibited different
      waveforms while the respective response fields could overlap substantially,
      suggesting that input from multiple sites converged but by engaging different
      neural circuits. The earliest deflection in the evoked potential ranged from 2 to
      10 msec. No differences were noted between language-dominant and language
      nondominant hemispheres.

PMID- 17534936
TI  - Disynaptic and polysynaptic statocyst pathways to an identified set of premotor
      nonspiking interneurons in the crayfish brain.
AB  - Nonspiking giant interneurons (NGIs) in the crayfish brain occupy a key position
      in the neuronal circuit for eyestalk motor control and, hence, play a crucial
      role in the central compensation process following unilateral deprivation of the
      statocyst that functions as an equilibrium sensory system. The synaptic
      organization of their input pathways, however, remains unknown. In the present
      study we identified 11 local interneurons that were polysynaptically connected to
      NGIs by making simultaneous intracellular recordings. We also identified three
      other local interneurons that connected to NGIs monosynaptically. PLNI-2 was a
      nonspiking interneuron making an excitatory synaptic connection to an NGI that
      had its cell body on the opposite side. PLSI was a spiking interneuron that made
      an inhibitory connection to an ipsilateral NGI. These cells were entirely
      confined to the protocerebrum. Another local spiking interneuron termed UGLI-1
      was found to make an excitatory connection with a contralateral NGI, extending
      dendrites in the anterior and posterior medial protocerebral neuropils and the
      lateral antenna I neuropil in the deutocerebrum where statocyst afferents
      project. When a depolarizing current was injected into the UGLI-1, the frequency
      of discrete excitatory PSPs increased remarkably in the postsynaptic NGI, each
      PSP following the UGLI-1 spike in one-to-one correspondence. The UGLI was
      previously reported to be activated monosynaptically by statocyst afferents. The
      present study thus finally demonstrates the tri-synaptic organization of the
      statocyst-to-eyestalk motor neuron pathway in its simplest form, suggesting the
      critical role of the UGLI-1 in the central compensation.

PMID- 17534937
TI  - Distribution of 26RFa binding sites and GPR103 mRNA in the central nervous system
      of the rat.
AB  - The novel RFamide peptide 26RFa, the endogenous ligand of the orphan receptor
      GPR103, affects food intake, locomotion, and activity of the gonadotropic axis.
      However, little is known regarding the localization of 26RFa receptors. The
      present report provides the first detailed mapping of 26RFa binding sites and
      GPR103 mRNA in the rat central nervous system (CNS). 26RFa binding sites were
      widely distributed in the brain and spinal cord, whereas the expression of GPR103
      mRNA was more discrete, notably in the midbrain, the pons, and the medulla
      oblongata, suggesting that 26RFa can bind to a receptor(s) other than GPR103.
      Competition experiments confirmed that 26RFa interacts with an RFamide peptide
      receptor distinct from GPR103 that may be NPFF2. High densities of 26RFa binding
      sites were observed in olfactory, hypothalamic, and brainstem nuclei involved in
      the control of feeding behavior, including the piriform cortex, the ventromedial
      and dorsomedial hypothalamic nuclei, the paraventricular nucleus, the arcuate
      nucleus, the lateral hypothalamic area, and the nucleus of the solitary tract.
      The preoptic and anterior hypothalamic areas were also enriched with 26RFa
      recognition sites, supporting a physiological role of the neuropeptide in the
      regulation of the gonadotropic axis. A high density of 26RFa binding sites was
      detected in regions of the CNS involved in the processing of pain, such as the
      dorsal horn of the spinal cord and the parafascicular thalamic nucleus. The wide
      distribution of 26RFa binding sites suggests that 26RFa has multiple functions in
      the CNS that are mediated by at least two distinct receptors.

PMID- 17534939
TI  - Lamotrigine-induced bilateral ballism.

PMID- 17534940
TI  - Differential expression of Sox2 and Sox3 in neuronal and sensory progenitors of
      the developing inner ear of the chick.
AB  - The generation of the mechanosensory elements of the inner ear during development
      proceeds in a precise temporal and spatial pattern. First, neurosensory
      precursors form sensory neurons. Then, prosensory patches emerge and give rise to
      hair and supporting cells. Hair cells are innervated by cochleovestibular neurons
      that convey sound and balance information to the brain. SOX2 is an HMG
      transcription factor characteristic of the stem-cell genetic network responsible
      for progenitor self-renewal and commitment, and its loss of function generates
      defects in ear sensory epithelia. The present study shows that SOX2 protein is
      expressed in a spatially and temporally restricted manner throughout development
      of the chick inner ear. SOX2 is first expressed in the neurogenic region that
      gives rise to sensory neurons. SOX2 is then restricted to the prosensory patches
      in E4 and E5 embryos, as revealed by double and parallel labelling with SOX2 and
      Tuj1, MyoVIIa, or Islet1. Proliferating cell nuclear antigen labelling showed
      that SOX2 is expressed in proliferating cells during those stages. By E5, SOX2 is
      also expressed in the Schwann cells of the cochleovestibular ganglion, but not in
      the otic neurons. At E8 and E17, beyond stages of sensory cell specification,
      SOX2 is transiently expressed in hair cells, but its level remains high in
      supporting cells. SOX3 is concomitantly expressed with SOX2 in the neurogenic
      domain of the otic cup, but not in prosensory patches. Our data are consistent
      with a role for SOX2 in specifying a population of otic progenitors committed to
      a neural fate, giving rise to neurons and hair cells.

PMID- 17534941
TI  - Emerging patterns of risk factor make-up enable subclassification of rheumatoid
      arthritis.

PMID- 17534942
TI  - RIM3gamma is a postsynaptic protein in the rat central nervous system.
AB  - RIMs (Rab3-interacting molecules) are synaptic proteins essential for neural
      transmission and plasticity. RIM1alpha has been implicated in membrane
      trafficking and regulation of secretory vesicle exocytosis in eukaryotic cells.
      Little information is as yet available on RIM3gamma. In the present study, we
      investigated the cellular expression, subcellular distribution, and possible
      functions of RIM3gamma in the rat CNS. Rim3gamma cDNA was subcloned and the
      protein expressed in vitro for the generation and purification of a rabbit anti
      RIM3gamma polyclonal antibody. In situ hybridization histochemistry,
      immunohistochemistry, and immunoelectron microscopy were performed to map
      expression of the mRNA and protein in the rat CNS. Our results indicated
      widespread distribution of RIM3gamma in diverse CNS neuronal cell types. The mRNA
      was found mainly in the cell bodies, whereas the protein immunoreactivity was
      localized chiefly to neuronal dendrites and to the postsynaptic densities as
      visualized under the light and electron microscope. This postsynaptic placement
      of RIM3gamma is distinct from the presynaptic localization of RIM1alpha but may
      contribute to regulating synaptic transmission and plasticity. The identification
      of RIM3gamma as a postsynaptic protein has functional implications for CNS
      synapse functions.

PMID- 17534943
TI  - Treatment with levodopa and risk for malignant melanoma.
AB  - A large follow-up study in Denmark of 14,088 patients in whom Parkinson's disease
      was diagnosed at hospital showed a twofold higher incidence of malignant melanoma
      in these patients than in the general population. In a nested case-control study
      of 45 patients with malignant melanoma, 97 patients with nonmelanoma skin cancer,
      and 172 control subjects, we investigated the hypothesis that treatment with
      levodopa increases the risk for skin cancer. Information on diagnoses and
      treatment was retrieved from medical records. We observed a significant fourfold
      to fivefold increase in the risk for malignant melanoma in a subgroup of patients
      with a probable diagnosis of idiopathic Parkinson's disease as compared with
      other patients. There was apparently no effect of levodopa on the risk for
      malignant melanoma as indicated by an odds ratio of 1.0 (95% confidence interval,
      0.8-1.3) per 1,000 g cumulative intake of the drug. We conclude that the
      increased rate of malignant melanoma observed in patients treated at hospital for
      Parkinson's disease is restricted to those with idiopathic Parkinson's disease,
      however, unrelated to the treatment with levodopa.

PMID- 17534944
TI  - Controlled study of decision-making and cognitive impairment in Parkinson's
      disease.
AB  - Impulse control disorders (ICD) related to reward-processing dysfunction have
      been reported in Parkinson's disease (PD). The relationship between clinical
      markers of limbic dysfunction with demographic variables and cognitive status of
      PD is incompletely known. Our objective was to further characterize the
      relationship between limbic and cognitive dysfunction in a representative sample
      of nondemented PD patients without antecedents of ICD, as assessed by a risk
      taking test of decision-making and a comprehensive neuropsychological battery.
      Prospective, controlled study of 35 nondemented PD patients and 31 matched
      controls who received the Iowa gambling task (IGT), the Mattis Dementia Rating
      Scale (MDRS) and verbal fluencies for global cognitive function, the Stroop and
      digit span tests for executive function, and the Rey Auditory Verbal Learning
      Test for memory. Compared to controls, PD patients performed significantly worse
      on the IGT. No clear relationship with demographic variables including
      dopaminergic treatment and motor response to levodopa (stable or fluctuating)
      emerged. Performance on the IGT was not related to executive function. In
      contrast, an inverse relationship was found between the IGT and memory and global
      cognitive performance, with patients with the better MDRS and memory scores
      performing significantly worse on the IGT. Our results confirm subclinical
      dysfunction of the limbic system in nondemented PD patients. Although impaired
      decision-making appears unrelated to executive dysfunction, patients with the
      better cognitive status appears more prone to assume risky behaviors.

PMID- 17534945
TI  - Myopathy as a first symptom of Huntington's disease in a Marathon runner.
AB  - A semi professional marathon runner at risk for Huntington's disease (HD) (43 CAG
      repeats) developed signs of a slowly progressive myopathy with exercise-induced
      muscle fatigue, pain, elevated creatine kinase level, and worsening of his
      running performance many years before first signs of chorea were detected. Muscle
      biopsy displayed a mild myopathy with mitochondrial pathology including a complex
      IV deficiency and analysis of the patient's fibroblast culture demonstrated
      deficits in mitochondrial function. Challenging skeletal muscle by excessive
      training might have disclosed myopathy in HD even years before the appearance of
      other neurological symptoms.

PMID- 17534946
TI  - Neuroanatomical relations of prothoracicotropic hormone neurons with the
      circadian timekeeping system in the brain of larval and adult Rhodnius prolixus
      (Hemiptera).
AB  - This paper reports the localization in the Rhodnius prolixus brain of neurons
      producing the key neuropeptide that regulates insect development,
      prothoracicotropic hormone (PTTH) and describes intimate associations of the PTTH
      neurons with the brain circadian timekeeping system. Immunohistochemistry and
      confocal laser scanning microscopy revealed that the PTTH-positive neurons in
      larvae are located in a single group in the lateral protocerebrum. Their number
      increases from two in the last larval instar to five during larval-adult
      development. In adults, there are two distinct groups of these neurons composed
      of two cells each. A daily rhythm in content of PTTH-positive material occurs in
      both the somata and the axons in both larval and adult stages. These rhythms
      correlate with previous evidence of a circadian rhythm of PTTH release from
      brains in vitro. The key circadian clock cells of Rhodnius are eight neurons,
      which co-express pigment-dispersing factor (PDF) and the canonical clock proteins
      PER and TIM; PDF fills the axons. Equivalent cells control behavioral rhythms in
      other insects. Double labeling revealed intimate associations between axons of
      larval PTTH neurons and clock neurons, indicating a neuronal pathway from the
      brain timekeeping system for circadian control of PTTH release. Additional PDF
      neurons appear in the adult, associated with the second group of PTTH neurons.
      These findings provide the first direct evidence that neurons of the insect brain
      timekeeping system control hormone rhythms. The range of functions regulated by
      this timekeeping system is quite similar to those of the vertebrate
      suprachiasmatic nucleus, for which the insect system is a valuable model.

PMID- 17534948
TI  - Analysis of olfactory function and the depth of olfactory sulcus in patients with
      Parkinson's disease.
AB  - Olfactory deficit is known to occur frequently in Parkinson's disease (PD). This
      study aimed to explore olfactory deficit in PD and to investigate its possible
      correlation with the disease severity or the depth of the olfactory sulcus. Fifty
      nine PD patients and 25 normal controls were examined by the odor identification
      test with the crosscultural smell identification test (CC-SIT). Among these
      subjects, the depth of the olfactory sulcus of 42 PD patients and 8 controls was
      measured in the plane of the posterior tangent through the eyeballs using the
      coronal view brain MRI. The CC-SIT scores of the PD patients were significantly
      lower than those of the normal control (P<0.001). However, CC-SIT did not
      correlate with the disease duration, H-Y stage, score of UPDRS Part III, or the
      depth of either side of the olfactory sulcus (P>0.05). Our study confirms that CC
      SIT is a helpful test in detecting the olfactory deficit in Korean PD patients.
      The absence of correlation of olfactory deficit with the disease severity or the
      depth of olfactory sulcus may suggest that olfactory loss precede the development
      of motor signs and not be a primary consequence of damage to the olfactory
      sulcus.

PMID- 17534947
TI  - Histological asymmetries of primary motor cortex predict handedness in
      chimpanzees (Pan troglodytes).
AB  - Like humans, chimpanzees display robust and consistent hand preferences during
      the performance of certain tasks. Although correlations have been demonstrated
      between gross anatomic measures of primary motor cortex asymmetry and handedness
      in captive chimpanzees, the relationship between histological architecture and
      behavioral lateralization has not yet been investigated. Therefore, we examined
      interhemispheric asymmetry of several different microstructural characteristics
      of the primary motor cortex in the region of hand representation from 18
      chimpanzees tested on a coordinated bimanual task before death. At the population
      level our data showed leftward bias for higher layer II/III neuron density. Of
      note, however, there was no population-level asymmetry in the areal fraction of
      Nissl-stained cell bodies, a finding that differs from previous studies of this
      cortical region in humans. Nonetheless, we found that asymmetry in the density of
      layer II/III parvalbumin-immunoreactive interneurons was the best predictor of
      individual hand preference. These results suggest that histological asymmetries
      are related to handedness in chimpanzees, while overall patterns of asymmetry at
      the population level might differ from humans.

PMID- 17534949
TI  - Neuropathological study 16 years after autologous adrenal medullary
      transplantation in a Parkinson's disease patient.
AB  - To date, there is no clinicopathological correlation of adrenal medullary
      transplant cases in patients with survival beyond a few years. Postmortem
      examination of a brain from a patient with Parkinson's disease (PD), 16 years
      after autologous adrenal medullary transplant, was performed using tyrosine
      hydroxylase (TH) and chromogranin A. The patient experienced a four-year initial
      improvement in motor function followed by resumption of the progressive nature of
      her disease that continued until her death. She expired 16 years following
      grafting. At autopsy, TH stain of the brain revealed severe loss of TH
      immunoreactivity in the substantia nigra and Lewy bodies, confirming the
      diagnosis of PD. The transplant site was identified by the presence of scarring
      and there was complete absence of any TH staining cells at the site of the
      transplant. There were few surviving cells staining with chromogranin A. The
      absence of TH-staining cells in the transplant 16 years after surgery provides
      further evidence that adrenal medullary transplants do not survive in the long
      term.

PMID- 17534950
TI  - Restless legs syndrome in Parkinson's disease and other neurodegenerative
      diseases of the central nervous system.
AB  - The pathophysiology of restless legs syndrome (RLS) is associated with central
      dopaminergic system dysfunction leading to speculations that RLS may be common in
      those neurodegenerative diseases with dopaminergic cell loss. However, since RLS
      is a very common condition, the co-occurrence with less frequent disorders such
      as the neurodegenerative diseases might be a matter of chance. Currently, no data
      suggests that patients with sporadic and familial RLS are at increased risk for
      developing a neurodegenerative disease. In particular, whether RLS is associated
      with Parkinson's disease has not been established. Only a few studies have
      directly addressed this issue, and these have methodological limitations yielding
      conflicting results. Few studies have assessed the frequency of RLS in other
      neurodegenerative disorders. In several autosomal dominant spinocerebellar
      ataxias, particularly in Machado-Joseph disease, a higher frequency of RLS is
      reported than could be accounted for in the general population. Two anecdotal
      publications have reported the presence of RLS in patients with Huntington's
      disease and hereditary spastic paraparesis. There are no studies that have
      examined the association between RLS and other neurodegenerative diseases, such
      as Alzheimer's disease, frontotemporal dementia, dementia with Lewy bodies,
      multiple system atrophy, progressive supranuclear palsy, and corticobasal
      degeneration. .

PMID- 17534951
TI  - Mild Parkinsonian signs: An overview of an emerging concept.
AB  - Mild Parkinsonian signs (MPS) include gait and balance changes, rigidity,
      bradykinesia, and tremor. MPS can occur commonly during the clinical examination
      of older people who do not have known neurological disease, with prevalence
      estimates for MPS as a whole ranging from 15% to 95%. MPS are generally
      progressive and they are coupled with functional difficulties, impaired gait and
      balance, and increased risks of mild cognitive impairment, dementia, and
      mortality. The mechanistic basis for these signs is unclear, but is likely to be
      multifactorial, with possible factors including an age-associated decline in
      dopaminergic nigrostriatal activity, the early development of neurodegenerative
      (Lewy body or Alzheimer's type) pathologies in the basal ganglia, or the
      accumulation of vascular pathology in the brain. It would be valuable to identify
      those individuals with MPS who are at increased risk for the development of
      future Alzheimer's disease, full-blown Parkinson's disease, or strokes, and to
      develop therapeutic strategies to intervene to lessen the likelihood of MPS
      related morbidity and mortality.

PMID- 17534952
TI  - Sparing of the substantia nigra in sporadic Creutzfeldt-Jakob disease presenting
      as an acute corticobasal syndrome.

PMID- 17534953
TI  - Basal ganglia cholinergic and dopaminergic function in progressive supranuclear
      palsy.
AB  - Progressive Supranuclear Palsy (PSP) is a progressive neurodegenerative disorder.
      In contrast to Parkinson's disease (PD) and dementia with Lewy bodies (DLB),
      replacement therapy with dopaminergic and cholinergic agents in PSP has been
      disappointing. The neurochemical basis for this is unclear. Our objective was to
      measure dopaminergic and cholinergic receptors in the basal ganglia of PSP and
      control brains. We measured, autoradiographically, dopaminergic (dopamine
      transporter, 125I PE2I and dopamine D2 receptors, 125I epidepride) and
      cholinergic (nicotinic alpha4beta2 receptors, 125I 5IA85380 and muscarinic M1
      receptors, 3H pirenzepine) parameters in the striatum and pallidum of
      pathologically confirmed PSP cases (n=15) and controls (n=32). In PSP, there was
      a marked loss of dopamine transporter and nicotinic alpha4beta2 binding in the
      striatum and pallidum, consistent with loss of nigrostriatal neurones. Striatal
      D2 receptors were increased in the caudate and muscarinic M1 receptors were
      unchanged compared with controls. These results do not account for the poor
      response to dopaminergic and cholinergic replacement therapies in PSP, and
      suggest relative preservation of postsynaptic striatal projection neurones
      bearing D2/M1 receptors.

PMID- 17534955
TI  - Impact of pramipexole on the onset of levodopa-related dyskinesias.
AB  - Dyskinesias are a major complication of dopaminergic therapy in the long-term
      treatment of Parkinson's disease. In the CALM-PD trial, subjects were initially
      randomized to levodopa or pramipexole and could later add levodopa if needed.
      After adjusting for disease duration and daily levodopa dosage, the incidence of
      dyskinesias after initiating levodopa was not significantly different among
      subjects initially randomized to levodopa and those initially randomized to
      pramipexole.

PMID- 17534956
TI  - Mirror writing in task specific dystonia: A case report.

PMID- 17534957
TI  - A novel GLRA1 mutation in a recessive hyperekplexia pedigree.
AB  - We report the identification of a novel Y228C mutation within the M1 trans
      membrane domain of the GLRA1 subunit of the glycine receptor responsible for a
      severe recessive hyperekplexia phenotype in a Kurdish pedigree.

PMID- 17534958
TI  - Tic suppression in the treatment of Tourette's syndrome with exposure therapy:
      the rebound phenomenon reconsidered.
AB  - Exposure and response prevention (ER), a behavioral treatment program consisting
      of exposure to premonitory sensory experiences during prolonged tic suppression,
      was shown to be a promising new treatment for tics in Tourette's syndrome (TS).
      In this study, the commonly reported paradoxical increase in tic frequency
      following voluntary tic suppression, i.e., rebound phenomenon, was examined. Tic
      frequency was rated in 20 TS patients during 15-minute videotaped conversations
      taken both before and following 10 ER sessions. In addition, tic frequency was
      obtained at home by family members of the patients during 15-minute daily tic
      frequency registrations. Ratings following ER sessions were compared with ratings
      obtained before the sessions. Neither the ratings at the institute nor the
      ratings at home supported a rebound effect following ER tic suppression.

PMID- 17534959
TI  - Levodopa responsiveness in disorders with parkinsonism: a review of the
      literature.
AB  - A literature review was conducted to investigate whether or not levodopa (LD)
      responsiveness (LR) is a useful criterion in the diagnosis of parkinsonian
      disorders. Although LR does appear to differ among the parkinsonian disorders,
      there is considerable confusion in the literature. While most patients with
      Parkinson's disease (PD) have a sustained benefit from LD, a small minority of
      patients with documented PD do not respond. The literature suggests that the LR
      rate is higher for multiple system atrophy (MSA), progressive supranuclear palsy
      (PSP), and corticobasal degeneration (CBD) than based on published diagnostic
      criteria. Magnitude and duration of response to LD and tolerability (time course,
      type and distribution of dyskinesias, mental effects and motor worsening) may be
      useful features in distinguishing PD, MSA, PSP, and CBD. Efforts should be
      directed toward better defining LR when used for diagnostic purposes and in
      scientific publications.

PMID- 17534961
TI  - Bupropion-induced parkinsonism.

PMID- 17534960
TI  - Biotransformation of D-methionine into L-methionine in the cascade of four
      enzymes.
AB  - D-Methionine was converted to L-methionine in a reaction system where four
      enzymes were used. D-amino acid oxidase (D-AAO) from Arthrobacter protophormiae
      was used for the complete conversion of D-methionine to 2-oxo-4-methylthiobutyric
      acid. Catalase was added to prevent 2-oxo-4-methylthiobutyric acid
      decarboxylation. In the second reaction step, L-phenylalanine dehydrogenase (L
      PheDH) from Rhodococcus sp. was used to convert 2- oxo-4-methylthiobutyric acid
      to L-methionine, and formate dehydrogenase (FDH) from Candida boidinii was added
      for NADH regeneration. Enzyme kinetics of all enzymes was analyzed in detail.
      Mathematical models for separate reactions steps, as well as for the complete
      system were developed and validated in the batch reactor experiments. Complete
      conversion of D-methionine to L-methionine was achieved. Considering that both
      enzymes act on different substrates, such a system could be easily employed for
      the synthesis of other amino acids from D-isomer, as well as from the racemate of
      a certain amino acid (DL-amino acid).

PMID- 17534962
TI  - Comment on Shpirer et al. ("Excessive daytime sleepiness in patients with
      Parkinson's disease: a polysomnographic study").

PMID- 17534963
TI  - A nationwide survey of excessive daytime sleepiness in Parkinson's disease in
      France.
AB  - To determine the prevalence of excessive daytime sleepiness (EDS) and that of
      dozing and sudden onset of sleep episodes (SOS) while driving in ambulatory
      patients with Parkinson's disease (PD) in France, a national sample of private
      and public neurologists was asked to recruit the first 10 consecutive nondemented
      PD patients. Each patient completed a questionnaire including the Epworth
      Sleepiness Scale (ESS) and the likelihood of dozing off and experiencing SOS
      episodes behind the wheel. Clinical and demographic data were collected. One
      thousand six hundred and twenty-five patients with PD were included in the
      survey. Twenty-nine percent of the patients suffered from EDS (ESS score>or=10)
      but only 0.8% declared a high chance of dozing while driving and 0.5% reported
      totally unpredictable SOS episodes while driving. Risk factors for EDS were male
      gender, reduced activity of daily living, and a high daily levodopa equivalent
      dosage. Risk factors for SOS episodes while driving were an ESS score>or=10, male
      gender, and low Hoehn and Yahr staging. EDS is common in ambulatory patients with
      PD and is a major risk factor for dozing and for SOS episodes behind the wheel in
      patients who drive.

PMID- 17534964
TI  - Worsening of motor symptoms and gynecomastia during spironolactone treatment in a
      patient with Parkinson's disease and congestive heart failure.

PMID- 17534965
TI  - Re: pitfalls in non-therapeutic research in children.

PMID- 17534966
TI  - Hiccup secondary to dopamine agonists in Parkinson's disease.

PMID- 17534967
TI  - Assessment of restless legs syndrome--methodological approaches for use in
      practice and clinical trials.
AB  - The Restless Legs Syndrome (RLS) is a sensorimotor disorder that has only
      recently been extensively investigated by validated methods. Following the first
      presentation of diagnostic criteria by the International RLS Study Group in 1995,
      several methods were specifically developed for clinical trials in RLS or adapted
      from other areas of medicine and health sciences. We present a critical overview
      on validated methods to assess (1) severity of RLS symptoms [International RLS
      Rating Scale (IRLS), John Hopkins RLS Severity Scale (JHRLSSS), the RLS-6 scales,
      and the investigator-based Clincial Global Impressions (CGI)]; (2) quality of
      life [RLS Quality of Life Instrument (RLS-QLI), Hopkins RLS Quality of Life
      Questionnaire (RLSQoL), and the RLS Quality of Life Questionnaire (QoL-RLS)]; (3)
      sleep disturbances and sudden onset of sleep; (4) sleep laboratory methods
      (polysomnography, limb activity monitoring by actigraphy) to evaluate sleep and
      periodic leg movements (including the "suggested immobilization test"); and (5)
      severity of augmentation (Augmentation Severity Rating Scale, ASRS). It is
      concluded that several validated methods are available to investigate the main
      features of RLS in practice and in clinical trials; however, further developments
      are needed to address new questions like the consequences of RLS on life
      functioning in areas such as ability to travel, days missed at work or impaired
      work performance.

PMID- 17534968
TI  - Predictors for snoring in children with rhinitis at age 5.
AB  - Snoring is often found in allergic diseases and may be an early manifestation of
      more serious sleep-disordered breathing. We aimed to investigate whether the risk
      factors for snoring among pre-school children with rhinitis are similar to those
      for allergic diseases in a birth cohort. The study cohort was drawn from
      participants in the Childhood Asthma Prevention Study (CAPS). This is a
      randomized controlled trial of dietary intervention and house dust mite avoidance
      during the first 5 years of life, aimed at reducing the risk of acquiring asthma
      and other allergic conditions in children at high-risk for allergic diseases.
      Parents of children with symptoms of rhinitis at age 5 years (n = 219 out of 516
      cohort members) were asked if their child snored: 127 (60%) reported some snoring
      and 56 (26%) snored more than three times per week. Multiple logistic regression
      analyses indicated that children who were first-born (adjusted odds ratio, 2.50,
      95% CI 1.20-5.21), were exposed to maternal tobacco smoke during the first year
      of life (2.40, 1.1-5.25), or who had asthma (2.51, 1.14-5.55) and/or eczema
      (2.29, 1.02-5.13) at age 5 years were more likely to snore. Birth-weight, body
      mass index at age 4.5, spirometry, and breastfeeding were not related to snoring.
      Risk factors for snoring are similar to risk factors for allergic disorders.
      Snoring may be part of the allergic spectrum of diseases. Our data may contribute
      to clinician's ability to effectively screen for snoring in preschool children.

PMID- 17534970
TI  - DNA fragmentation in developing lung fibroblasts exposed to Stachybotrys
      chartarum (atra) toxins.
AB  - Stachybotrys chartarum (atra) is a toxic mold that grows on water-damaged
      cellulose-based materials. Research has revealed also that inhalation of S.
      chartarum spores caused marked changes in respiratory epithelium, especially to
      developing lungs. We analyzed the epigenetic potential of S. chartarum spore
      toxins on developing rat lung fibroblasts using single cell gel electrophoresis
      (comet assay). Isolated fetal lung fibroblasts were exposed to S. chartarum spore
      toxins for 15 min, 3, 14, or 24 hr and control cells were exposed to saline under
      the same conditions. Cells were embedded in agarose, electrophoresed under
      alkaline conditions and silver stained. DNA damage was assessed in terms of
      fragmentation as measured by comet tail length (DNA migration) and intensity (%
      DNA contained within head and tail). Upon visual inspection, control fibroblasts
      showed no DNA fragmentation whereas S. chartarum-treated cells had definable
      comets of various degrees depending upon the time-course. Analyses of the comets
      revealed that exposure to S. chartarum spore toxins for at least 15 min to 14 hr,
      induced increased DNA fragmentation in a time-dependent manner. The fact that
      exposure to toxins for 24 hr showed less damage suggested that developing lung
      fibroblasts may have the capability of repairing DNA fragmentation.

PMID- 17534969
TI  - Duration of treatment effect after tobramycin solution for inhalation in young
      children with cystic fibrosis.
AB  - RATIONALE: Among young children with cystic fibrosis (CF), Pseudomonas aeruginosa
      (Pa) airway infection is associated with increased morbidity and mortality. Early
      intervention strategies include tobramycin solution for inhalation (TSI), which
      can eradicate lower airway Pa from cultures obtained at the end of 28 days of
      treatment in young children. METHODS: We conducted an open label, sequential
      cohort study of TSI in young children with CF to investigate duration of
      antimicrobial treatment effect. The primary outcome was lower airway Pa
      eradication per bronchoalveolar lavage (BAL) fluid culture. Sequential treatment
      cohorts varied by duration of treatment (28 or 56 days) and timing of follow-up
      BAL (at Days 56, 84, or 112). Subjects (N = 36) were treated with TSI, 300 mg
      twice daily, for 28 days or 56 days per cohort assignment. RESULTS: Among 31
      evaluable subjects, culture based, lower airway Pa eradication was observed in
      the majority of subjects for up to 1-3 months following TSI treatment: 75% in
      Cohort 28/56 (days of treatment/day of follow-up BAL), 63% in Cohort 28/84, 82%
      in Cohort 56/112, and 75% in Cohort 28/112. Non-mucoid Pa at baseline and/or
      exotoxin A seronegativity were associated with higher rates of eradication. There
      was a less pronounced effect of TSI treatment on Pa eradication from
      oropharyngeal cultures in all cohorts. TSI treatment was associated with reduced
      neutrophilic airway inflammation and was not related to any serious adverse
      events. CONCLUSION: TSI monotherapy is safe and can eradicate lower airway Pa for
      up to 3 months after treatment in young children with CF.

PMID- 17534971
TI  - Improved learning and memory of contextual fear conditioning and hippocampal CA1
      long-term potentiation in histidine decarboxylase knock-out mice.
AB  - Some studies suggest that the histaminergic system plays an important role in
      learning and memory. However, the results seem to be controversial in many
      behavioral tasks. In the present study, we used HDC knockout (HDC-KO) mice to
      investigate the effects of long-term histamine deficiency on learning and memory
      in contextual fear conditioning. We found that HDC-KO mice exhibited improved
      contextual fear from 1 day after training and this lasted for at least 14 days
      when compared with the wild-type (WT) controls. Cued fear was also improved 2
      days after training in HDC-KO mice. Moreover, injection of histamine
      (intracerebroventricularly, 10 microg/mouse) immediately after training reversed
      the improvement in contextual fear conditioning when tested 1 day after training.
      Electrophysiological data showed that hippocampal CA1 long-term potentiation
      (LTP) in HDC-KO mice was much greater than that in WT mice, and paired-pulse
      facilitation decreased 2 h after LTP induction in HDC-KO mice. In contrast, HDC
      KO mice showed smaller LTP than did WT mice 1 day after training. Hippocampal
      glutamate levels significantly increased in HDC-KO mice 1 and 4 days after
      training. The results indicated that histamine deficiency may improve
      consolidation of contextual fear conditioning. This improvement may be due to the
      increased hippocampal CA1 LTP, and presynaptic glutamate release. The
      relationship between behavior and synaptic plasticity provides support for the
      involvement of activity-dependent LTP in learning and memory.

PMID- 17534972
TI  - Tyrosine phosphorylation of the GluR2 subunit is required for long-term
      depression of synaptic efficacy in young animals in vivo.
AB  - The study of the intracellular mechanics that underlay changes in synaptic
      efficacy is a rapidly evolving field of research. It is currently believed that
      NMDA receptors play a significant role in the induction of synaptic plasticity,
      whereas AMPA receptors play a significant role in its expression. For AMPA
      receptors, it has been shown that tyrosine phosphorylation of the GluR2 carboxyl
      termini is required for the expression of long-term depression of synaptic
      efficacy (LTD) in vitro (Ahmadian et al. (2004) EMBO J 23:1040-1050). In the
      present study, we sought to determine whether similar mechanisms are involved in
      vivo, where different stimulation parameters are required for the induction of
      LTD. We initially used a paired-burst (PB) paradigm that reliably induces LTD in
      vivo. In these animals we were able to prevent the induction and expression of PB
      LTD by administering a peptide (GluR-3Y) that acted as a competitive inhibitor of
      tyrosine phosphorylation. In a separate set of animals, we exposed animals to
      brief periods of stress (S) before using low-frequency stimuli to induce LTD (S
      LTD). Again, GluR2-3Y blocked both the induction and expression of S-LTD. In
      contrast, an inert version of the peptide, with alanine replacing the three
      tyrosine residues, did not inhibit LTD induction. In addition, we demonstrated
      that GluR2-3Y did not affect the induction of long-term potentiation in vivo.
      These findings support the hypothesis that tyrosine phosphorylation and AMPA
      receptor endocytosis are necessary steps for the induction and maintenance of two
      forms of LTD in the CA1 region.

PMID- 17534973
TI  - Palivizumab prophylaxis: how to compare pre- and post-prophylaxis eras?

PMID- 17534976
TI  - Age and gender specific lung function predictive equations provide similar
      predictions for both a twin population and a general population from age 6
      through adolescence.
AB  - BACKGROUND: There have been numerous studies of asthma in twins, but no study has
      evaluated whether lung function predictive models yield similar results between
      twin and general populations. We sought to evaluate this in late childhood and
      adolescent subjects. METHODS: We generated cross-sectional, sex- and age-specific
      regression models of FEV(1), and FVC, in a community-based cohort of 3140
      healthy, non-smoking Chinese twins using generalized estimating equations to
      adjust for correlations within twin pairs. We applied the model to a healthy non
      smoking general population cohort of 2187 subjects from the same region, and
      compared %predicted FEV(1) and FVC values between the two populations. RESULTS:
      Stratified by age and sex, the associations of height with FEV(1) or FVC varied
      by age group. During the adolescent growth spurt (age 13 for girls and ages 14-16
      for boys), the associations of height with FEV(1) or FVC were nonlinear and
      greater than that seen at other ages. During adolescence, FEV(1) and FVC for a
      given height increased with age. The percent predicted values of FEV(1) and FVC
      in the twin population were similar to that of the general population.
      CONCLUSIONS: Twin and general populations have similar patterns of lung function
      change over middle childhood and adolescence. Similar equations may be used to
      estimate percent predicted values. Finally, a single prediction equation cannot
      completely describe patterns of lung function from childhood through adolescence
      due to puberty related changes.

PMID- 17534977
TI  - Systemic cytokine profile in children with community-acquired pneumonia.
AB  - OBJECTIVES: Characterization of the systemic cytokine response in community
      acquired pneumonia (CAP) may facilitate our understanding of the host immune
      response and provide a prognostic as well as diagnostic tool. Systemic cytokine
      characterization of CAP has been limited largely to a few integral cytokines in
      adults. METHODS: Analyses were performed to investigate whether significant
      relationships existed between an expanded serum cytokine profile and etiologies,
      manifestations, and outcomes of pediatric CAP. The serum concentrations of 15
      cytokines were investigated in 55 hospitalized children with well-characterized
      CAP. RESULTS: Comparison of median cytokine concentrations among patients with
      CAP caused by Mycoplasma pneumoniae or Chlamydophila pneumoniae, Streptococcus
      pneumoniae, viruses, mixed infections, or unidentified pathogens revealed
      significant differences in IFN-alpha, IL-6, IL-17, GM-CSF, and TNF-alpha
      concentrations. The mixed infections category had significantly elevated
      concentrations of IFN-alpha, IL-6, GM-CSF, and TNF-alpha. There were significant
      correlations between concentrations of IL-6 and markers of disease severity
      (white blood cell band-forms, procalcitonin, and unequivocal consolidation). No
      single cytokine could reliably differentiate the etiologic cause of pneumonia.
      CONCLUSIONS: IL-6 is the only one of 15 serum cytokines studied that correlated
      with indicators of disease severity in childhood CAP. The applicability of
      cytokine profiles to identify microbiologic etiologies of pneumonia remains to be
      defined.

PMID- 17534978
TI  - Exposure to environmental tobacco smoke among children presenting to the
      emergency department with acute asthma: a multicenter study.
AB  - Environmental tobacco smoke (ETS) exposure has been associated with increased use
      of the emergency department (ED) for acute asthma care. The purpose of this study
      was to determine the prevalence of ETS exposure among children presenting to the
      ED for acute asthma care and whether ETS exposure affects acute asthma severity
      or response to therapy. We conducted a multi-center study of children 2-11 years
      with physician-diagnosed acute asthma presenting to 44 EDs in 18 states. Chi
      square test, Student's t-test, Wilcoxon rank sum test, and logistic regression
      were used for the analyses. The study population included 954 children. Thirty
      six percent (95% CI, 33-39%) of caregivers reported that their child was exposed
      to ETS. Among exposed children, 35% were exposed 1-6 days/week, and 65% were
      exposed daily. Compared to unexposed children, ETS-exposed children were older at
      asthma diagnosis, older at ED presentation, and were less likely to be Hispanic.
      Indicators of chronic asthma severity were higher among unexposed children (i.e.,
      total number of medications, use of controller medications, use of beta(2)
      agonists, number of urgent clinic visits, and lifetime hospitalizations). There
      was a weak association between ETS and acute asthma severity. Response to therapy
      (including ED disposition) did not differ between groups. On multivariate
      analysis, ETS-exposed children were more likely to be older, female, non
      Hispanic, have lower household income, not use controller medications, and have a
      pet at home (all P < 0.05). Our study showed that the prevalence of ETS exposure
      among children presenting to the ED with acute asthma differs across demographic
      factors. There were no significant differences in acute asthma symptoms or
      response to ED therapy between ETS-exposed and unexposed children. Lower use of
      controller medications and less frequent urgent clinic visits among ETS-exposed
      children suggest inadequate asthma care or milder disease. The weak association
      between ETS exposure and acute asthma severity might reflect confounding by
      psychological factors and/or chronic asthma severity. The frequency of ETS
      exposure suggests that the ED may be an appropriate venue to engage caregivers of
      children with asthma in asthma education and smoking cessation efforts.

PMID- 17534979
TI  - RhDNase before airway clearance therapy improves airway patency in children with
      CF.
AB  - INTRODUCTION: Little is known about the optimal timing of rhDNase nebulization in
      relation to airway clearance therapy (ACT). OBJECTIVE: To compare the effects of
      rhDNase before ACT versus rhDNase after ACT in children with CF. METHODS: 
      DESIGN: randomized, double blind, double dummy, cross over study. INCLUSION
      CRITERIA: CF, stable clinical condition, rhDNase maintenance therapy. Children in
      Group I inhaled rhDNase 30 minutes before ACT, and placebo directly after ACT in
      week 1-3. The protocol was reversed during week 4-6. Group II performed the
      reversed sequence. Patients continued their daily routine ACT. Primary endpoint:
      MEF(25) %pred. Pulmonary functions tests were performed on days 0, 14, 21, 35 and
      42. In weeks 3 and 6 children scored cough and sputum production on daily diary
      cards. RESULTS: 24 patients completed the study. Mean age = 12 years (range 7
      19). Mean MEF(25) %pred was 5.8% higher after 3 weeks of rhDNase before ACT,
      compared to rhDNase after ACT (58.3% vs 52.5%, p=0.01). There were no significant
      differences for any of the other variables. CONCLUSION: Inhalation of rhDNase
      before ACT improves peripheral airway patency in children with cystic fibrosis.
      Since all children were already on maintenance rhDNase therapy before the study,
      this effect is additional to any existing effect of regular rhDNase.

PMID- 17534980
TI  - Blepharospasm and limb dystonia caused by Mohr-Tranebjaerg syndrome with a novel
      splice-site mutation in the deafness/dystonia peptide gene.
AB  - Mohr-Tranebjaerg syndrome (MTS) is an X-linked disorder characterized by
      childhood-onset progressive deafness, dystonia, spasticity, mental deterioration,
      and blindness. It is due to mutations in the deafness/dystonia peptide (DDP1)
      gene. We describe a sporadic 42-year-old man with MTS presenting with postlingual
      deafness, adult-onset progressive dystonia with marked arm tremor, mild
      spasticity of the legs, and visual disturbance due to a novel mutation (g to a
      transition at the invariant gt of the 5' splice donor site of exon 1) in the DDP1
      gene. This case, and a review of previously reported cases, highlights a variety
      of potential diagnostic pitfalls in this condition.

PMID- 17534981
TI  - Autopsy case of opsoclonus-myoclonus-ataxia and cerebellar cognitive affective
      syndrome associated with small cell carcinoma of the lung.
AB  - We report an autopsy case of paraneoplastic opsoclonus-myoclonus-ataxia syndrome
      associated with small cell carcinoma of the lung. Chemotherapy and lung lobectomy
      resulted in complete tumor remission and disappearance of myoclonus. However,
      emotional and behavioral disturbances relapsed and remitted associated with
      exacerbation of truncal ataxia and ocular flutter, which responded favorably to
      prednisolone. At autopsy, after 2 years and 11 months of illness, there was no
      recurrence of cancer. Neuropathologically, only the cerebellum was affected, with
      diffuse loss of Purkinje cells and dentate neurons, suggesting that the
      paraneoplastic cerebellar involvement may be responsible for the cognitive
      affective symptoms in our patient.

PMID- 17534982
TI  - Pathological crying induced by deep brain stimulation.
AB  - Pathological crying (PLC)--an affective gesture without any or an adequate
      emotion--occurs with various diseases. A recent theory suggests that PLC is
      caused by a disruption of higher order cortical association areas from the
      cerebellum which computes profiles of psychomotor responses. We report a patient
      with Parkinson's disease who developed PLC during stimulation of the subthalamic
      nucleus (STN) predominantly of the right hemisphere. Positron emission tomography
      imaging showed thalamo-ponto-cerebellar activation during such stimulation. These
      findings indicate that the STN and possibly also ponto-cerebellar pathways are
      involved in psychomotor control and in the modulation of PLC.

PMID- 17534983
TI  - What happened when I took OAB drugs?

PMID- 17534984
TI  - Treatment of carpal tunnel syndrome.
AB  - Fifty years after its widespread recognition, a significant minority of patients
      with carpal tunnel syndrome continue to experience poor outcomes from treatment.
      Much current treatment is supported by an inadequate or nonexistent evidence
      base. Surgical decompression, often considered the definitive solution, gives
      excellent results in only 75% of cases in ordinary practice and leaves 8% of
      patients worse than previously. The only other interventions that are clearly of
      benefit are neutral-angle wrist splinting, with a success rate of 37%, and
      steroids, which are better given by local injection than as oral treatment. The
      initial response rate to injection is 70% but there are frequent relapses.
      Nevertheless, these conservative treatments have a negligible incidence of
      serious complications and should be used more widely until surgical failures can
      be reduced to similar levels.

PMID- 17534985
TI  - Roof-shaped pyrazaboles as a structural motif for bent-core liquid crystals.

PMID- 17534986
TI  - Organocatalytic enantioselective [3+2] cycloaddition of azomethine ylides and
      alpha,beta-unsaturated aldehydes.

PMID- 17534987
TI  - A one-pot synthesis of primary amides from aldoximes or aldehydes in water in the
      presence of a supported rhodium catalyst.

PMID- 17534988
TI  - Nucleophilic addition of organometallic reagents to cinchona alkaloids: simple
      access to diverse architectures.

PMID- 17534989
TI  - The cyclotide fingerprint in oldenlandia affinis: elucidation of chemically
      modified, linear and novel macrocyclic peptides.
AB  - The complete suite of cyclotides present in Oldenlandia affinis (Rubiaceae), the
      plant that was originally found to contain this unique family of circular
      proteins, has been characterised. This study expands the number of known
      cyclotides in this plant to 17, of which nine new sequences (kalata B9-B17) were
      characterised in this work. In addition, five derivatives that contain oxidation
      products of the conserved tryptophan were identified, and it was shown that the
      formation of these derivatives is catalysed by exposure to sunlight. Furthermore,
      we describe two "linear" cyclotide analogues. These acyclic peptides have three
      intact disulfide bonds, and their N and C termini coincide with the hypothesised
      cleavage sites from the precursor protein. This work increases our knowledge
      about the sequence variation that is accommodated by the cyclic cystine knot
      scaffold, confirms its applicability as a template for drug design, and also
      shows the first natural degradation pathways for cyclotides. These pathways have
      important implications for the persistence and environmental fate of the
      cyclotides if used as crop-protection agents.

PMID- 17534990
TI  - Polymer grafting from CdS quantum dots via AGET ATRP in miniemulsion.
AB  - We report the synthesis of CdS quantum dot (QD)-poly(acrylate) nanocomposites
      using a recently developed catalytic system where activators are generated by
      electron transfer for atom-transfer radical polymerization (ATRP) in a
      miniemulsion. The QD surface was functionalized with a tris(alkyl)phosphine,
      previously modified with an ATRP chlorine initiator, and subsequent controlled
      polymerization was carried out from the functionalized surface of nanoparticles.
      The final material showed a high homogeneity and the QDs were evenly dispersed.
      The optical-absorption edge in the visible spectra of the nanocomposites attests
      the presence of the CdS QDs. Quantum confinement effects were assigned, though a
      blue shift in relation to the optical spectrum of the initial QDs has been
      observed.

PMID- 17534991
TI  - De novo asymmetric synthesis of the anthrax tetrasaccharide by a palladium
      catalyzed glycosylation reaction.

PMID- 17534992
TI  - Architectures from aligned nanotubes using controlled micropatterning of silicon
      substrates and electrochemical methods.

PMID- 17534993
TI  - "Jelly dots": synthesis and cytotoxicity studies of CdTe quantum dot-gelatin
      nanocomposites.

PMID- 17534994
TI  - Single-crystalline and near-monodispersed NaMF3 (M = Mn, Co, Ni, Mg) and LiMAlF6
      (M = Ca, Sr) nanocrystals from cothermolysis of multiple trifluoroacetates in
      solution.
AB  - We report the synthesis of single-crystalline and near-monodispersed NaMF3 (M =
      Mn, Co, Ni, Mg), LiMAlF6 (M = Ca, Sr), and NaMgF3:Yb,Er nanocrystals (quasisquare
      nanoplates, nanorods, and nanopolygons) by the cothermolysis of multiple
      trifluoroacetates in hot combined organic solvents (oleic acid, oleylamine, and 1
      octadecene). The nanocrystals were characterized by XRD, TEM, superconductive
      quantum interference device (SQUID), and upconversion luminescence spectroscopy.
      By regulating the polarity of the dispersant, the NaMF3 (M = Mn, Co, Ni)
      nanoplates were partially aligned to form nanoarrays on copper TEM grids. The
      sizes of the NaMF3 nanocrystals were easily tuned by the use of proper synthetic
      conditions such as reaction temperature and time and solvent composition. On the
      basis of a series of experiments in which the reaction conditions were varied,
      together with GC-MS and FTIR analysis, the reaction pathways for the formation of
      these nanocrystals from trifluoroacetate precursors were proposed. The magnetic
      measurements showed that the differently sized NaMnF3 square plates displayed
      interesting weak ferromagnetic behavior on the nanometer scale. The strong red
      upconversion luminescence emitted from the NaMgF3:Yb,Er nanorods under 980-nm
      near-IR laser excitation suggests that NaMgF3 may be a good candidate host
      material for red upconversion luminescence.

PMID- 17534995
TI  - Iron-complex-catalyzed C-C bond cleavage of organonitriles: catalytic metathesis
      reaction between H-Si and R-CN bonds to afford R-H and Si-CN bonds.
AB  - The first example of the catalytic C-CN bond cleavage of acetonitrile as well as
      Si-CN bond formation have been achieved in the photoreaction of MeCN with Et3SiH
      promoted by [Cp(CO)2FeMe]. This catalytic system is applicable to other
      organonitriles. Several iron complexes [(eta(5)-C5R5)(CO)2FeR'] (R5 = H5, H4Me,
      Me5, H4SiMe3, H4I, H4P(O)(OMe)2; R' = SiMe3, CH2Ph, Me, Cl, I) were examined as
      catalyst, and [Cp(CO)2FeMe] was found to be the best precursor. A catalytic
      reaction cycle was proposed, which involves oxidative addition of Et3SiH to
      [Cp(CO)FeMe], reductive elimination of CH4 from [Cp(CO)FeMe(H)(SiEt3)],
      coordination of RCN to [Cp(CO)Fe(SiEt3)], silyl migration from Fe to N in the
      coordinated RCN, and dissociation of Et3SiNC from Fe. The reaction with MeCN of
      [Cp(CO)Fe(py)(SiEt3)], which was newly prepared and determined by X-ray analysis,
      and the reaction of Et3SiH with MeCN in the presence of a catalytic amount of
      [Cp(CO)Fe(py)(SiEt3)] showed that the 16-electron species [Cp(CO)Fe(SiEt3)] is
      the active species in the catalytic cycle (TON up to 251).

PMID- 17534996
TI  - Controlled fabrication of highly oriented ZnO microrod/microtube arrays on a zinc
      substrate and their photoluminescence properties.
AB  - Well-aligned zinc oxide microrod and microtube arrays with high aspect ratios
      were fabricated on zinc foil by a simple solution-phase approach in an aqueous
      solution of ethylenediamine (en). The shape of the ZnO microstructures can be
      easily modulated from rods to tubes by adding cetyl trimethyl ammonium bromide
      (CTAB) into the reaction system. Control experiments demonstrate that some
      reaction parameters, such as the concentration of ethylenediamine, the kind of
      surfactant, reaction time, and the temperature, all have direct influences on the
      morphology of the products. Based on the early structure arising from arrested
      growth (nanosheets), a reasonable mechanism for the growth of ZnO microrods and
      microtubes has been proposed. The products were characterized by X-ray powder
      diffraction (XRD), scanning electron microscopy (SEM), transmission electron
      microscopy (TEM), and photoluminescence emission.

PMID- 17534997
TI  - Towards a bio-based industry: benign catalytic esterifications of succinic acid
      in the presence of water.
AB  - The biorefinery of the future will need to integrate bioconversion and
      appropriate low environmental impact chemical technologies (Green Chemistry) so
      as to produce a wide range of products from biomass in an economically effective
      and environmentally acceptable manner. The challenge for chemists is to develop
      chemistry that works with fermentation-derived dilute, aqueous mixtures of
      oxygenated chemicals (platform molecules) rather than the petroleum-derived non
      aqueous, non-oxygenated feedstocks we have been working with for 50+ years and to
      avoid energy intensive and wasteful concentration and purification steps. Here we
      show that a new family of tuneable mesoporous carbonaceous catalysts derived from
      starch can be used to accomplish efficient chemistry in aqueous solution. Our new
      aqueous catalytic chemistry relies on the ability to adjust the surface
      properties including the hydrophobicity-hydrophilicity balance of mesoporous
      Starbons by carbonisation at different temperatures (250-750 degrees C). Simple
      treatment of these materials with sulfuric acid then provides a series of porous
      solid acids that can function under a range of conditions including dilute
      aqueous solution. The reactions of succinic acid (platform molecule) in aqueous
      alcohol demonstrate the outstanding activities of these new catalysts.

PMID- 17534998
TI  - Photosensitization and the photocurrent switching effect in nanocrystalline
      titanium dioxide functionalized with iron(II) complexes: a comparative study.
AB  - Selected iron(II) complexes (ferrocene, ferrocenylboronic acid,
      hexacyanoferrate(II)) have been used as photosensitizers of titanium dioxide.
      Various types of electronic interactions between the surface complex and the
      semiconducting support are reflected in different yields of photocurrent
      generated upon visible-light irradiation and different efficiencies of the
      photosensitization effect. The studied systems, showing the photocurrent
      switching upon changes of electrode potential and energy of photons (the PEPS
      effect), are good models of simple photoelectrochemical logic devices. The
      mechanism of photosensitization and photocurrent switching is discussed with
      respect to the type of surface-complex-support interaction. Quantum-mechanical
      calculations support the proposed mechanisms.

PMID- 17534999
TI  - Choline-derivative-based ionic liquids.
AB  - A total of sixty-three choline derivative-based ionic liquids in the forms of
      chlorides, acesulfamates, and bis(trifluoromethylsulfonyl)imides have been
      prepared and their physical properties (density, viscosity, solubility, and
      thermal stability) have been determined. Thirteen of these salts are known
      chlorides: precursors to the 26 water-soluble acesulfamates, 12 acesulfamates
      only partially miscible with water, and 12 water-insoluble imides. The crystal
      structures for two of the chloride salts-(2
      hydroxyethyl)dimethylundecyloxymethylammonium chloride and
      cyclododecyloxymethyl(2-hydroxyethyl)dimethylammonium chloride-were determined.
      The antimicrobial (cocci, rods, and fungi) activities of the new hydrophilic
      acesulfamate-based ILs were measured and 12 were found to be active. The
      alkoxymethyl(2-hydroxyethyl)dimethylammonium acesulfamates have been shown to be
      insect feeding deterrents and thus open up a new generation of synthetic
      deterrents based on ionic liquids. The alkoxymethyl(2
      decanoyloxyethyl)dimethylammonium bis(trifluoromethylsulfonyl)imides have also
      been shown to act as fixatives for soft tissues and can furthermore be used as
      substitutes for formalin and also preservatives for blood.

PMID- 17535000
TI  - C-H activation and C=C double bond formation reactions in iridium ortho-methyl
      arylphosphane complexes.
AB  - The Vaska-type iridium(I) complex [IrCl(CO){PPh(2)(2-MeC(6)H(4))}(2)] (1),
      characterized by an X-ray diffraction study, was obtained from iridium(III)
      chloride hydrate and PPh(2)(2,6-MeRC(6)H(3)) with R=H in DMF, whereas for R=Me,
      activation of two ortho-methyl groups resulted in the biscyclometalated
      iridium(III) compound [IrCl(CO){PPh(2)(2,6-CH(2)MeC(6)H(3))}(2)] (2). Conversely,
      for R=Me the iridium(I) compound [IrCl(CO){PPh(2)(2,6-Me(2)C(6)H(3))}(2)] (3) can
      be obtained by treatment of [IrCl(COE)(2)](2) (COE=cyclooctene) with carbon
      monoxide and the phosphane in acetonitrile. Compound 3 in CH(2)Cl(2) undergoes
      intramolecular C-H oxidative addition, affording the cyclometalated hydride
      iridium(III) species [IrHCl(CO){PPh(2)(2,6-CH(2)MeC(6)H(3))}{PPh(2)(2,6
      Me(2)C(6)H(3))}] (4). Treatment of 2 with Na[BAr(f) (4)] (Ar(f)=3,5
      C(6)H(3)(CF(3))(2)) gives the fluxional cationic 16-electron complex
      [Ir(CO){PPh(2)(2,6-CH(2)MeC(6)H(3))}(2)][BAr(f) (4)] (5), which reversibly reacts
      with dihydrogen to afford the delta-agostic complex [IrH(CO){PPh(2)(2,6
      CH(2)MeC(6)H(3))}{PPh(2)(2,6-Me(2)C(6)H(3))}][BAr(f)(4)] (6), through cleavage of
      an Ir-C bond. This species can also be formed by treatment of 4 with
      Na[BAr(f)(4)] or of 2 with Na[BAr(f)(4)] through C-H oxidative addition of one
      ortho-methyl group, via a transient 14-electron iridium(I) complex. Heating of
      the coordinatively unsaturated biscyclometalated species 5 in toluene gives the
      trans-dihydride iridium(III) complex [IrH(2)(CO){PPh(2)(2,6
      MeC(6)H(3)CH=CHC(6)H(3)Me-2,6)PPh(2)}][BAr(f) (4)] (7), containing a trans
      stilbene-type terdentate ligand, as result of a dehydrogenative carbon-carbon
      double bond coupling reaction, possibly through an iridium carbene species.

PMID- 17535001
TI  - Comparative study of metal-catalyzed iminations of sulfoxides and sulfides.
AB  - A comparative study of the imination of sulfur compounds with various metal
      catalysts in combination with isolated or in situ generated iminoiodinanes
      (PhI==NR) as nitrogen sources is presented. The influence of the metal catalyst
      towards the imination of a variety of substituted sulfoxides has been evaluated.
      Moreover, the effect of the different oxidation states of sulfur on the
      reactivity and selectivity of the nitrogen transfer redox process in the
      formation of sulfilimines and sulfoximines was studied. Depending on both the
      specific metal catalyst as well as the employed nitrene precursor, the
      sulfide/sulfoxide imination ratio varied in transformations of thianthrene-5
      oxide and substituted para-thio phenylsulfoxides.

PMID- 17535002
TI  - Self-assembly of nanosize coordination cages on si(100) surfaces.
AB  - Bottom-up fabrication of 3D organic nanostructures on Si(100) surfaces has been
      achieved by a two-step procedure. Tetradentate cavitand 1 was grafted on the Si
      surface together with 1-octene (Oct) as a spatial spectator by photochemical
      hydrosilylation. Ligand exchange between grafted cavitand 1 and self-assembled
      homocage 2, derived from cavitand 5 bearing a fluorescence marker, led to the
      formation of coordination cages on Si(100). Formation, quantification, and
      distribution of the nanoscale molecular containers on a silicon surface was
      assessed by using three complementary analytical techniques (AFM, XPS, and
      fluorescence) and validated by control experiments on cavitand-free silicon
      surfaces. Interestingly, the fluorescence of pyrene at approximately 4 nm above
      the Si(100) surface can be clearly observed.

PMID- 17535003
TI  - Triplex molecular beacons as modular probes for DNA detection.

PMID- 17535004
TI  - Bismuth and lead hanging-carboxylate porphyrins: an unexpected homobimetallic
      lead(II) complex.

PMID- 17535005
TI  - Silver-catalyzed intermolecular amination of C--H groups.

PMID- 17535006
TI  - Switching the interior hydrophobicity of a self-assembled spherical complex
      through the photoisomerization of confined azobenzene chromophores.

PMID- 17535007
TI  - 'Is there a case for using visual analogue scale valuations in CUA' by Parkin and
      Devlin. A response: 'yes there is a case, but what does it add to ordinal data?'.

PMID- 17535009
TI  - OFT, VBP: QED?
AB  - The report by the Office of Fair Trading (OFT) on the UK pharmaceutical price
      regulation scheme (PPRS) recommends the reform of the current scheme, which is a
      combination of profit and price controls, to one where price is based on the
      health benefits offered by a pharmaceutical. On closer examination some of the
      more commonly expressed concerns about these proposals do not seem to be well
      founded. In principle, the OFT's recommendations may contribute to allocative and
      dynamic efficiency in the NHS. However, there are some dangers and the details of
      how it will be implemented are crucial. For example, value-based pricing with an
      inappropriate threshold for cost-effectiveness, or an inappropriate pricing
      structure, could lead to technologies being adopted at prices where their
      benefits, in terms of health outcome, do not offset the health displaced
      elsewhere in the NHS, a situation in which the NHS is damaged rather than
      improved by innovation. A failure to account for uncertainty and the value of
      evidence in negotiating prices and coverage could also undermine the evidence
      base for future NHS practice. Whatever view is taken, the OFT report will
      inevitably shape the scope of future policy debates about value, guidance, price
      and innovation.

PMID- 17535010
TI  - Use of liquid chromatography-atmospheric pressure chemical ionization-ion trap
      mass spectrometry for identification of oleanolic acid and ursolic acid in
      Anoectochilus roxburghii (wall.) Lindl.
AB  - Oleanolic acid (OA) and ursolic acid (UA) are the two important bioactive
      compounds in Anoectochilus roxburghii (wall) Lindl (A. roxburghii), which has
      been used as a traditional Chinese medicine. So far, there has been no report to
      indicate that A. roxburghii contains these two bioactive compounds. It is
      necessary to develop an effective method to extract and analyze OA and UA in A.
      roxburghii. In this paper, a quantitative method, consisting of supercritical
      fluid extraction (SFE) followed by liquid chromatography-atmospheric pressure
      chemical ionization-ion trap mass spectrometry (LC-APCI-IT-MS) analysis, was
      developed for identification of OA and UA in A. roxburghii. The extraction was
      carried out by using CO(2) as the supercritical fluid and ethanol as the modifier
      before LC separation. The mobile phase used for LC separation consisted of acetic
      acid (1%, v/v), water (15%, v/v) and methanol (84%, v/v), and the elution was
      performed at a flow rate of 0.8 ml/min. The mass spectrometer was operated in
      APCI(+) mode with selected ion monitoring (SIM) to quantify OA and UA at m/z
      439.4. Under optimum conditions, the linear responses of OA and UA were obtained
      in the concentration range of 0.5-80 (r = 0.9992) and 0.5-50 microg/ml (r =
      0.9989) with the detection limits of 0.125 and 0.085 microg/ml, respectively. The
      proposed method has been used for the identification and quantitation of OA and
      UA in a real A. roxburghii sample.

PMID- 17535011
TI  - Structural identification of trace level enol tautomer impurity by on-line
      hydrogen/deuterium exchange HR-LC/MS in a LTQ-Orbitrap hybrid mass spectrometer.

PMID- 17535012
TI  - Optimal treatment for severe neurogenic bowel dysfunction after chronic spinal
      cord injury: a decision analysis.
AB  - BACKGROUND: When conservative management fails in patients with chronic spinal
      cord injury (SCI) and neurogenic bowel dysfunction, clinicians have to choose
      from a variety of treatment options which include colostomy, ileostomy, Malone
      anterograde continence enema (MACE) and sacral anterior root stimulator (SARS)
      implantation. This study employed a decision analysis to examine the optimal
      treatment for bowel management of young individuals with chronic refractory
      constipation in the setting of chronic SCI. METHODS: A decision analysis was
      created to compare the four surgical strategies using baseline analysis, one-way
      and two-way sensitivity analyses, 'worst scenario' and 'best scenario'
      sensitivity analyses, and probabilistic sensitivity analyses. Quality-adjusted
      life expectancy (QALE) was the primary outcome. RESULTS: The baseline analysis
      indicated that patients who underwent the MACE procedure had the highest QALE
      value compared with the other interventions. Sensitivity analyses showed that
      these results were robust. CONCLUSION: The MACE procedure may provide the best
      long-term outcome in terms of the probability of improving bowel function,
      reducing complication rates and the incidence of autonomic dysreflexia, and being
      congruent with patients' preferences. The analysis was sensitive to changes in
      assumptions about quality of life/utility, and thus the results could change if
      more specific estimates of utility became available.

PMID- 17535013
TI  - Routine early laparoscopic cholecystectomy for acute cholecystitis after
      conclusion of a randomized controlled trial.
AB  - BACKGROUND: The aim of this retrospective review was to assess the clinical
      outcomes of laparoscopic cholecystectomy for acute cholecystitis since the
      conclusion of a randomized controlled trial in 1997. METHODS: Records of all
      patients admitted for acute cholecystitis in whom early laparoscopic
      cholecystectomy was attempted between July 1997 and December 2004 were reviewed.
      RESULTS: A total of 209 patients were recruited to this study. Forty-three
      surgeons performed the procedures. The conversion rate increased significantly in
      the early period after the trial from 21 per cent to 42 per cent (39 of 92
      patients) and decreased significantly to 24 per cent (13 of 54 patients) in the
      later period. The proportion of operations performed by higher surgical trainees
      increased significantly from 17 per cent in the early period to 56 per cent in
      the later period. This increase was associated with a fall in conversion rate
      without any significant increase in duration of operation or complication rate.
      CONCLUSION: This study has demonstrated that the results achieved in a randomized
      trial can be translated into clinical practice by the entire surgical unit. A
      structured training programme with the inclusion of an experienced surgeon
      assisting both trainees and specialists should minimize this learning curve.

PMID- 17535014
TI  - Gastric perforation during endoscopic resection for gastric carcinoma and the
      risk of peritoneal dissemination.
AB  - BACKGROUND: The potential risk of peritoneal seeding following perforation caused
      by endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD)
      is unknown. METHODS: Between January 1991 and December 2003, 90 patients suffered
      gastric perforation during EMR or ESD at the National Cancer Centre Hospital,
      Tokyo. The clinical and pathological evidence for peritoneal dissemination in
      these patients was assessed retrospectively. RESULTS: Eighty-four patients were
      followed up at this hospital for a median of 53.6 (range 7.0-136.6) months; the
      remaining six patients were followed up at other institutions. In 83 patients the
      perforation was repaired by endoscopic clip application and seven patients
      underwent emergency surgery. Gastrectomy was carried out in 33 patients who had
      non-curative endoscopic surgery. Among these, peritoneal fluid was sampled during
      operation in nine patients and was cytologically negative for malignancy. The
      other 24 patients who had a gastrectomy did not have ascites so cytology was not
      performed. No peritoneal dissemination was noted during follow-up. CONCLUSION:
      This study suggests that perforation associated with EMR and ESD does not lead to
      peritoneal dissemination even in the long term.

PMID- 17535015
TI  - Assessment of lung area in fetuses with congenital diaphragmatic hernia.
AB  - OBJECTIVE: To compare the intra- and interobserver agreement of three different
      methods of measuring lung area in fetuses with congenital diaphragmatic hernia
      (CDH). METHODS: In 71 fetuses with isolated CDH at 21-33 weeks' gestation, the
      area of the contralateral lung was assessed by firstly, manual tracing of lung
      borders, secondly, multiplication of the longest diameter of the lung by its
      widest perpendicular diameter, and thirdly, multiplication of the anteroposterior
      (AP) diameter of the lung at the mid-clavicular line by the perpendicular
      diameter at the midpoint of the AP diameter (AP method). In 30 fetuses the
      measurements were made by two observers and Bland-Altman analysis was used to
      compare the measurement agreement and bias for each observer and between the two
      observers. RESULTS: The area obtained by the AP method was similar to that
      obtained by the manual tracing method, but the area by the longest diameter
      approach was bigger by 34.4% (95% CI, - 2.4% to 71.1%). The 95% confidence
      intervals of the difference in paired measurements of lung areas by the same
      observer and by two different observers were narrower in the manual tracing
      method than in the multiplying diameters methods. CONCLUSIONS: In CDH the most
      reproducible measurement of fetal lung area is provided by manual tracing of the
      limits of the lungs, rather than by multiplication of lung diameters.

PMID- 17535016
TI  - Electrospray ionization-multistage tandem mass spectrometry of complex multitin
      organometallic compounds.
AB  - The series of 14 complex organotin(IV) compounds containing many tin atoms and
      noncovalent bonds in the structure was characterized by electrospray ionization
      multistage tandem mass spectrometry (ESI-MS(n)). The mass spectra were measured
      in both polarity modes to obtain complementary structural information. The
      characteristic pattern of ten natural tin isotopes allowed the determination of
      the number of tin atoms in the molecular adducts and fragment ions by comparing
      theoretical and experimental isotopic distributions. Positive ion ESI spectra
      show unusual adduct formation depending on the type of organic solvent used for
      the direct infusion analysis owing to the ion-molecule reactions in the ion
      source. On the basis of the detailed spectral interpretation of organotin(IV)
      compounds, the fragmentation patterns of multitin organometallic compounds have
      been proposed. Noncovalent bonds in polymeric complexes are fragmented first,
      which is then followed by characteristic neutral losses in monomeric units.

PMID- 17535017
TI  - Validation of direct injection electrospray LC-MS/MS for confirmation of opiates
      in urine drug testing.
AB  - A method based on the direct injection of diluted urine for the identification
      and quantification of morphine, morphine-3-glucuronide, morphine-6-glucuronide,
      codeine, codeine-6-glucuronide, ethylmorphine, ethylmorphine-6-glucuronide and 6
      acetylmorphine (6AM) in human urine by electrospray ionisation liquid
      chromatography-tandem mass spectrometry was validated for use as a confirmation
      procedure in urine drug testing. Four deuterium labelled analogues were used as
      internal standards: morphine-3-glucuronide-D3, morphine-D3, codeine-D3 and 6AM
      D3. Twenty microlitre aliquots of urine were mixed with 80 mul of the internal
      standard solution in autosampler vials and 10 mul was injected. The
      chromatographic system consisted of a 2.0 x 100 mm C18 column and the gradient
      elution buffers used acetonitrile and 25 mmol/l formic acid. Two product ions
      produced from the protonated molecular ions were monitored in the selected
      reaction monitoring mode. The intra- and inter-assay variability (coefficient of
      variation) was below 10% at higher levels for all analytes, but at the reporting
      limits the variation was above 20% for 6AM, morphine-3-glucuronide and codeine-6
      glucuronide. Ion suppression occurred early after injection but did not affect
      the identification and quantification of the analytes in authentic samples. The
      method was further validated by comparison with a reference gas chromatographic
      mass spectrometric method using authentic urine samples. The two methods agreed
      almost completely (99%) regarding the identified analytes, but for the
      quantitative results there were slightly lower levels when measuring glucuronides
      directly as compared to total determination after hydrolysis by gas
      chromatography-mass spectrometry. We conclude that the presented liquid
      chromatographic-tandem mass spectrometric method is robust and reliable, and
      suitable for use as a confirmation method in urine drug testing for opiates

PMID- 17535018
TI  - Associations between head circumference, leg length and dementia in a Korean
      population.
AB  - BACKGROUND: Adult leg length is influenced by nutritional intake in childhood.
      Shorter leg length has been found to be associated with adverse health outcomes
      in late life, including dementia. Smaller head circumference has also been found
      to be associated with dementia. The independence of these two potential markers
      of risk for dementia has not been investigated. METHODS: Community residents aged
      65 or over (n = 916) within a defined geographic area of South Korea were
      screened clinically for dementia and dementia subtypes. Data on anthropometric
      measures (head circumference and leg length), demographics (age, gender),
      apolipoprotein E, and early life environment (birth order, number of siblings,
      parental occupation, area of residence, education) were gathered. Reproductive
      history was also ascertained in women. RESULTS: Both smaller head circumference
      and shorter leg length were associated with increased age, rural residence in
      childhood and lower education. After adjustment for these factors, they were both
      independently associated with Alzheimer's disease but only in women. CONCLUSIONS:
      Smaller head size and shorter limb length were associated with lower early-life
      socio-economic status. Both factors were apparently independent markers of risk
      for dementia which may indicate risk factors occurring in childhood affecting
      both brain and skeletal development. Associations were principally present in
      women. Reasons for gender differences in associations require clarification but,
      for this population and age group, may include preferential treatment of male
      children.

PMID- 17535019
TI  - Modeling of ion processes in atmospheric pressure matrix-assisted laser
      desorption/ionisation.
AB  - Atmospheric pressure matrix-assisted laser desorption/ionization (AP-MALDI) has
      proven a convenient and rapid method for ion production in the mass spectrometric
      analysis of biomolecules. This technique, like other atmospheric pressure
      ionization methods, suffers from ion loss during ion transmission from the
      atmosphere into the vacuum of the mass spectrometer. In this work, a simple model
      describing ion formation and ion motion towards the inlet capillary of the mass
      spectrometer is described. Both the gas flow and electric field near the MALDI
      plate were numerically calculated using the boundary element method (BEM). The
      ions were moving along with the gas flow and drifting in the electric field in
      accordance with their ion mobility properties. The ion signal dependence on an
      electric field strength obtained in the proposed model correlates well with
      experimental results.

PMID- 17535020
TI  - Chemical routes for the transformation of biomass into chemicals.

PMID- 17535022
TI  - Recursive partitioning analysis of prognostic factors for patients with four or
      more intracranial metastases treated with radiosurgery.
AB  - The purpose of this study was to devise a new recursive partitioning analysis
      (RPA) of patients with four or more intracranial metastases treated with a single
      radiosurgery procedure to identify a class of patients with extended survival.
      205 patients underwent Gamma Knife radiosurgery for four or more intracranial
      metastases (median = 5, range 4-18) during one session. The median total
      treatment volume was 6.8 cc (range 0.6-51.0 cc). Radiosurgery was used as sole
      management (17% of patients), or in combination with WB-RT (46%), or after
      failure of WB-RT (38%). The median marginal radiosurgery dose was 16 Gy (range 12
      20 Gy). RPA assessed the effects of age, Karnofsky >70, extracranial disease,
      visceral metastases, number of metastases, total treatment volume, history of
      breast and melanoma primaries on survival. The median overall survival after
      radiosurgery for all patients was 8 months. RPA identified a favorable subgroup
      of 78 patients (43% of the series) with a total treatment volume <7 cc and < 7
      brain metastases (Class 1), with a median survival of 13 months. This subgroup's
      survival was significantly better (p <0.00005) than the remaining patients (Class
      2) (n=111) with a median survival of 6 months. In conclusion, RPA of multiple
      brain metastasis patients identified 2 distinct cohorts of patients. Class 1
      patients have a total treatment volume <7 cc and < 7 metastases (4-6) with
      favorable survival after Radiosurgery and Class 2 patients have a total treatment
      volume > or = 7 cc and/or > or = 7 metastases and have a significantly poorer
      survival.

PMID- 17535023
TI  - Intensity-modulated Radiosurgery for patients with brain metastases: a mature
      outcomes analysis.
AB  - The purpose of this study was to evaluate the outcomes of patients with brain
      metastases treated by tomotherapeutic Intensity-modulated Radiosurgery (IMRS).
      Using retrospective chart review, we analyzed the outcomes of 78 patients (age 33
      83 years, median 57 years) who underwent 111 sessions of IMRS (1 to 7 sessions
      per patient, median 1) for brain metastases (1 to 4 targets per IMRS session,
      median 1) treated between 2000 and 2005 using a serial tomotherapeutic intensity
      modulated radiotherapy treatment (IMRT) planning and delivery system (Peacock,
      Nomos Corp., Cranberry Township, PA). Treatment planning was performed using an
      inverse treatment planning optimization algorithm that was optimized for IMRS. A
      median prescription dose of 15 Gy in combination with WBI, and median 20 Gy for
      IMRS alone was delivered using 2-4 couch angles over 4-24 rotational arcs.
      Overall survival was calculated using Kaplan-Meier analysis. To determine the
      effects of prognostic variables on survival, univariate and multivariate analyses
      using proportional hazards were performed to assess the effects of age, tumor
      size, the combination with whole brain irradiation, presence of multiple brain
      metastases, and presence of extracranial disease. The median overall survival was
      6.5 months (95% CI, 5.5-7.9). One- and two-year survival rates were 24% and 10%.
      In multivariate analyses, age greater than 60 years was the only statistically
      significant variable that affected survival (hazard rate 1.29, p=0.049). We
      conclude that tomotherapeutic IMRS is safe and effective to treat patients with
      brain metastases.

PMID- 17535024
TI  - Fractionated stereotactic radiotherapy boost and weekly paclitaxel in malignant
      gliomas clinical and pharmacokinetics results.
AB  - Management of Malignant Gliomas continues to be a challenge. We prospectively
      studied the role of adding weekly Paclitaxel to Fractionated Stereotactic
      Radiation Therapy (FSRT) in the treatment of Malignant Gliomas. Twenty-three
      Glioblastoma Multiforme and two Anaplastic Astrocytoma were studied. Patients
      received 46 Gy at 2 Gy/fraction followed by a boost utilizing FSRT at a fraction
      of 2.5 Gy for 8 fractions. Paclitaxel is delivered concomitantly at 150 mg/m(2)
      weekly for six cycles. Eighteen patients had pharmacokinetic assays of Paclitaxel
      levels. All patients were followed until death or for a maximum of 36 months. The
      overall survival of the whole group was 14 months. The median survival for RPA
      prognostic classes III, IV, V, and VI were 20, 14, 12, and 11 months. Higher
      survival (14 months) was noted in the subtherapeutic phenytoin level group
      compared to 10 months in the therapeutic group (P=0.271). No grade 4 CTCAE
      (version 3.0) toxicities were observed. Enhanced survival was demonstrated with
      gross tumor resection (20.8 months), KPS > or =80 (18.7 months) and age < or =60
      years (27 months) as compared to subtotal resection or biopsy (12.1 months, P<
      0.005), KPS < or =70 (10.8 months, P=0. 005) and older age > 60 (10.46 months,
      P=0.006), respectively. Our study suggests that: i) the use of weekly Paclitaxel
      and FSRT in Gliomas is well tolerated with a survival of 14 months; ii) the
      regimen resulted in improvement of survival of RPA classes IV, V, VI; and iii)
      the use of FSRT boost may be studied with other chemotherapeutic agents to see if
      superior results can be attained.

PMID- 17535025
TI  - Fractionated stereotactic radiotherapy for pituitary adenomas following
      microsurgical resection: safety and efficacy.
AB  - The treatment of pituitary adenomas following medical management has historically
      involved surgical excision or stereotactic radiosurgery, with the two modalities
      often utilized collectively. However, there have been only a limited number of
      reports on the use of fractionated stereotactic radiotherapy (FSRT) for the
      treatment of pituitary adenomas. To enhance the existing knowledge regarding the
      safety and efficacy of this treatment modality, we describe our initial
      experience with FSRT for residual pituitary adenomas following microsurgical
      resection. From 1999 to 2005, 14 patients (7F, 7M) with residual pituitary
      adenomas (7 nonsecretory, 2 growth hormone secreting, 2 prolactin secreting, 2
      thyrotropin secreting, 1 adrenocorticotropic hormone secreting) underwent FSRT.
      All patients were planned using the Radionics X-Knife 3D planning system, and
      received a median dose of 50.4 Gy in daily 1.8 Gy fractions administered to the
      90% prescription isodose line. Treatments were delivered stereotactically using a
      dedicated Varian 6/100 linear accelerator, with immobilization achieved with the
      Gill-Thomas-Cosman relocatable head frame. Mean tumor size was 3.6 cm (median,
      3.2 cm), and mean patient age was 44.6 years (median, 47 years). The mean dosages
      to the optic chiasm and brainstem were 0.159 and 0.040 Gy (median, 0.163 and
      0.031 Gy) per fraction. All patients were evaluated with visual field testing and
      pre- and postgadolinium-enhanced magnetic resonance imaging at a minimum of one
      year follow-up (median, 22.5 months; mean, 27.8 months). Following FSRT, local
      control (defined as absence of tumor progression) was achieved in all fourteen
      patients. Three patients developed hypopituitarism (average, 30 months after
      treatment), with no patient experiencing visual changes or acute complications
      following FSRT. These results demonstrate the efficacy and safety of FSRT for
      achieving long-term local tumor control for pituitary adenomas, further
      validating this technique as an appropriate treatment modality for residual
      adenomas following microsurgery.

PMID- 17535026
TI  - Reducing set-up uncertainty in the Elekta Stereotactic Body Frame using
      Stealthstation software.
AB  - The Elekta Stereotactic Body Frame (SBF) is a device which allows extracranial
      targets to be localized and irradiated in a stereotactic coordinate system.
      Errors of positioning of the body relative to the frame are indirectly estimated
      by image fusion of multiple CT scans. A novel repositioning methodology, based on
      neurosurgical Stealth technology, is presented whereby accurate patient
      repositioning is directly confirmed before treatment delivery. Repositioning was
      performed on four extracranial stereotactic radiosurgery patients and a
      radiotherapy simulation phantom. The setup error was quantitatively measured by
      fiducial localization. A confirmatory CT scan was performed and the resulting
      image set registered to the initial scan to quantify shifts in the GTV isocenter.
      Alignment confirmation using Stealth took between 5 and 10 minutes. For the
      phantom studies, a reproducibly of 0.6 mm accuracy of phantom-to-SBF alignment
      was measured. The results on four actual patients showed setup errors of 1.5 mm
      or less. Using the Stealth Station process, rapid confirmation of alignment on
      the treatment table is possible.

PMID- 17535027
TI  - Automatic target localization and verification for on-line image-guided
      stereotactic body radiotherapy of the spine.
AB  - To facilitate image-guided stereotactic body radiotherapy (IG-SBRT) of spinal and
      paraspinal tumors, the authors have developed an on-line image registration
      system for automated target localization and patient position verification with
      high precision. When rotations are present in a patient's daily setup position, a
      setup error of a few millimeters can be introduced in localization of the
      isocenter by using surrounding bony structures. This setup error not only will
      deteriorate the dose coverage of the tumor, more importantly it will overdose the
      spinal cord. To resolve this issue, the image registration program developed by
      the authors detects translational shifts as well as rotational shifts using 3D CT
      image registration. Unacceptable rotations were corrected by either repositioning
      the patient or adjusting the treatment couch that was capable of rotational
      corrections when such a couch was available for clinical use. One pair of
      orthogonal digitally reconstructed radiographs (DRR) were generated from the
      daily pretreatment CT scan to compare with the corresponding DRRs generated from
      the planning CT scan to confirm the target shift correction. After the patient's
      position was corrected a pair of orthogonal portal images were taken for final
      verification. The accuracy of the image registration result was found to be
      within 0.1 mm on a head and neck phantom. Target shifts of a fraction of a
      millimeter were readily visible in our DRR comparison and portal image
      verification. The time needed to complete the image registration and DRR
      comparison was about 3 minutes. An integrated system that combines a high-speed
      CT scanner and a linear accelerator was used for imaging and treatment delivery.
      Application of the program in actual IG-SBRT cases demonstrated that it was
      accurate, fast, and reliable. It serves as a useful tool for image-guided
      radiotherapy where high precision of target localization is required.

PMID- 17535029
TI  - Generation and characterization of a proton microbeam for experimental
      radiosurgery.
AB  - A proton microbeam has been developed to support various research endeavors. Test
      subjects may be irradiated from any angle with respect to the vertical because
      the beamline is contained within a rotating gantry used for human patients.
      Converting from the treatment to experimental arrangement is quick and
      straightforward as is the reverse. Using a series of collimators, the final beam
      diameter at the surface of the subject is 1 mm. The depth from the surface to the
      Bragg peak in water is 15 mm. Fluence distributions perpendicular to the beam
      axis were determined by scanning radiographic film exposed at various depths with
      a scanner having a pixel size of 84.7 microm. The depth dose integrated over the
      beam area was measured using a parallel plate ionization chamber. Central axis
      depth doses were calculated by multiplying the ionization chamber signal by the
      ratio of film doses for the central axis pixels to the integrated beam doses at
      each depth. A Faraday cup was used to confirm the dose at the surface while TLDs,
      diodes, and film were used to verify the dose at depth. The usefulness of this
      beamline for experimental situations has been demonstrated in a feline
      neurological study. The dosimetry techniques are useful for narrow beams such as
      used for functional radiosurgery treatments of humans.

PMID- 17535028
TI  - Intensity-modulated radiosurgery: improving dose gradients and maximum dose using
      post inverse-optimization interactive dose shaping.
AB  - Intensity-modulated radiosurgery (IMRS) for brain metastases and arterio-venous
      malformations (AVM) using a serial tomotherapy system (Nomos Corp., Cranberry
      Township, PA) has been delivered in >150 cases over the last 5 years. A new
      software tool provided within the Corvus inverse planning software (ActiveRx)
      allows for post inverse planning re-optimization and individualization of the
      dose distribution. We analyzed this tool with respect to increasing the steepness
      of the dose gradient and in-target dose inhomogeneity while maintaining
      conformity. Fifteen clinically delivered IMRS plans for solitary brain metastases
      provided the basis for this analysis. The clinical IMRS plans were copied and the
      ActiveRx module was opened. The toolset in ActiveRx includes a hot spot eraser, a
      pencil tool to redefine isodose lines and a drag and drop tool, allowing
      reshaping of existing isodose lines. To assess changes in the steepness of the
      dose gradient and dose homogeneity, the 100%, 90%, 50% and 25% isodose volume,
      the volume of the target, maximum dose and mean dose to the target were recorded.
      We also recorded total monitor units and calculated treatment delivery times.
      Target volumes ranged from 0.6 to 14.1 cm(3) (mean/median 3.9/1.8 cm(3)). Mean
      RTOG conformity index (CI) of plans clinically delivered was 1.23+/-0.31; mean
      homogeneity index (HI) was 115+/-5%. After using the ActiveRx tool-set, the mean
      CI was slightly improved to 1.14+/-0.1, with an associated increase in HI to
      141+/-10%. The average, respective Ian Paddick CI for the 100%, 90% 50% and 25%
      isodose lines were 0.79 vs. 0.83, 0.44 vs. 0.59, 0.12 vs. 0.19, and 0.04 vs.
      0.07, representing significant improvements after using ActiveRx post
      optimization. Total MU were reduced by a mean of 12.3% using ActiveRx, shortening
      estimated treatment delivery times by 3.2 minutes on average. A post inverse
      planning optimization tool for IMRS plans allowed for statistically significant
      improvements in the steepness of the dose gradient, and increased maximum and
      mean target doses compared to clinically delivered plans that were already
      considered excellent. Gains were especially pronounced in the reduction of normal
      brain tissue included into the 90%, and 50% isodose lines. We have since made
      this process part of the clinical routine for all cranial IMRS procedures.

PMID- 17535030
TI  - Detection of metastases from gastrointestinal neuroendocrine tumors: prospective
      comparison of 18F-TOCA PET, triple-phase CT, and PET/CT.
AB  - The purpose of the investigation was to assess positron emission tomography
      (PET), computed tomography (CT) and the image fusion of PET and CT (PET/CT) in
      the detection of metastases from gastrointestinal neuroendocrine tumors. In a
      prospective study, thirty-one patients were consecutively examined using a state
      of-the-art PET/CT. PET was performed with a carbohydrated F-18-labeled
      somatostatin receptor ligand (Gluc-Lys([(18)F]FP-TOCA) from the base of the skull
      to the proximal thigh using a Pico-3D PET scanner. CT was performed with a
      noncontrast low-dose CT (LD-CT) and a venous-dominant contrast-enhanced CT (VD
      CT) from the base of the skull to the proximal thigh and a hepatic arterial
      dominant contrast-enhanced CT (AD-CT) from the epigastric region using a 16-slice
      CT. The data sets from PET and CT (LD-CT and VD-CT) were fused automatically. To
      assess a relative sensitivity of each imaging modality, the total number of
      metastases by summing the number of metastases depicted for each patient by the
      highest sensitive modality was used as reference standard. PET, LD-CT, AD-CT, VD
      CT, PET/LD-CT and PET/VD-CT showed a lesion-by-lesion based overall detection
      rate for liver metastases (n=858) of 90.8% (P<0.001), 29.4% (P<0.001), 45.5%
      (P<0.001), 73.9% (P<0.001), 91.5% (P<0.001) and 100%. PET, LD-CT, VD-CT, PET/LD
      CT and PET/VD-CT showed an overall detection rate for lymph node metastases
      (n=193) of 93.8% (P<0.001), 25.4% (P<0.001), 64.8% (P<0.001), 93.8% (P<0.001) and
      100% and for osseous metastases (n=567) of 98.6% (P<0.005), 40.7% (P<0.001),
      40.7% (P<0.001), 100% and 100%. Furthermore, PET revealed 2 (22.2%) of 9
      intrapulmonal lesions seen on LD-CT, VD-CT, PET/LD-CT and PET/VD-CT. PET as
      single modality revealed most liver, lymph node and osseous metastases. The
      combination of molecular/metabolic with anatomical/morphological information
      improves the diagnostic accuracy for the detection of metastases in comparison to
      any single imaging modality. LD-CT cannot replace VD-CT in the detection of liver
      and lymph node metastases, but was equal in the detection of osseous metastases
      and identifying of pulmonary lesions.

PMID- 17535031
TI  - Monitoring of chemotherapy-induced cell death in melanoma tumors by N,N'-Didansyl
      L-cystine.
AB  - Early assessment of the efficacy of anticancer agents is a highly desirable and
      an unmet need in clinical oncology. Clinical imaging of cell-death may be useful
      in addressing this need, as induction of tumor cell-death is the primary
      mechanism of action of most anticancer drugs. In this study, we examined the
      performance of N,N'-Didansyl-L-cystine (DDC), a member of the ApoSense family of
      novel small molecule detectors of cell-death, as a potential tool for monitoring
      cell-death in cancer models. Detection of cell-death by DDC was examined in
      fluorescent studies on B16 melanoma cells both in vitro and ex vivo following its
      in vivo administration. In vitro, DDC manifested selective uptake and
      accumulation within apoptotic cells that was highly correlated with Annexin-V
      binding, changes in mitochondrial membrane potential, and caspase activation.
      Uptake was not ATP-dependent, and was inducible by calcium mobilization. In vivo,
      DDC selectively targeted cells undergoing cell-death in melanoma tumors, while
      not binding to viable tumor cells. Chemotherapy caused marked tumor cell-death,
      evidenced by increased DDC uptake, which occurred before a detectable change in
      tumor size and was associated with increased animal survival. These data confirm
      the usefulness of imaging of cell-death by DDC as a tool for early monitoring of
      tumor response to anti-cancer therapy.

PMID- 17535032
TI  - Conductive interstitial thermal therapy (CITT) device evaluation in VX2 rabbit
      model.
AB  - We have developed a conductive interstitial thermal therapy (CITT) device to
      precisely and reliably deliver controlled thermal doses to the surgical margins
      at the cavity site following tumor resection, intraoperatively. The temperature
      field created by CITT ablation of a perfused tissue was modeled with a finite
      element package Femlab. The modeling suggested that a maximum probe temperature
      of 120 degrees C and an ablation time of 20 minutes were required to ablate
      highly perfused tissue such as the VX2 carcinoma. Deployable pins enable faster
      and more reliable thermal ablation. The model predictions were tested by thermal
      ablation of VX2 carcinoma tumors implanted in adult New Zealand rabbits. The size
      of the ablated region was confirmed with a viability stain, triphenyltetrazolium
      chloride (TTC). Histopathological examination revealed 3 regions in the ablated
      area: a carbonized region (1-3 mm); a region that contained thermally fixed
      cells; and an area of coagulated necrosis cells. Cells in the thermally fixed
      region stained for PCNA (proliferating cell nuclear antigen) and were bounded by
      the carbonized layer at the cavity wall, and by necrotic cells that exhibit
      nuclear fragmentation and cell dissociation, 5 to 10 mm away from the CITT probe.
      Adjacent tissue outside the target region was spared with a clear demarcation
      between ablated and normal viable tissue. It is suggested that the CITT device
      can be used, clinically, to inhibit local recurrence by creating negative
      surgical margins following the resection of a primary tumor in non-metastatic
      early staged tumors.

PMID- 17535033
TI  - Potential long-term consequences of fad diets on health, cancer, and longevity:
      lessons learned from model organism studies.
AB  - While much of the third world starves, many in the first world are undergoing an
      obesity epidemic, and the related epidemics of type II diabetes, heart disease,
      and other diseases associated with obesity. The amount of economic wealth being
      directly related to a decline in health by obesity is ironic because rich
      countries contribute billions of dollars to improve the health of their citizens.
      Nevertheless, nutritional experiments in model organisms such as yeast, C.
      elegans, Drosophila, and mice confirm that "caloric restriction" (CR), which is
      defined generally as a 30-40% decrease in caloric intake, a famine-like condition
      for humans seen only in the poorest of countries, promotes good health and
      increases longevity in model organisms. Because caloric restriction, and dieting
      in general, requires a great deal of will power to deal with the feelings of
      deprivation, many fad diets, such as the Atkins, South Beach, and Protein Power,
      have been developed which allow people to lose weight purportedly without the
      severe feelings of deprivation. However, the long-term effects of such fad diets
      are not known and few experiments have been performed in the laboratory to
      investigate possible side affects and adverse consequences. In this paper, we
      review studies with fad-like dietary conditions in humans and model organisms,
      and we propose a "Dietary Ames Test" to rapidly screen fad diets, dietary
      supplements, and drugs for potential long-term health consequences in model
      organisms.

PMID- 17535034
TI  - Cardiovascular Parameters during Submaximal Exercise following Submucous
      Administration of Articaine : A Comparison with Lidocaine and Placebo in Young
      Healthy Volunteers.
AB  - OBJECTIVE: Local anaesthetics have been shown to exert pronounced
      cardiodepressant effects after intravenous administration in high doses. Thus, we
      compared the cardiovascular effects of articaine with those of lidocaine and
      placebo after submucous administration in healthy volunteers during bicycle
      exercise ergometry. PARTICIPANTS AND METHODS: A single-blind, randomised, placebo
      controlled, crossover study design with washout periods of 1 week each between
      the three treatment days was used. Articaine 40mg (A), lidocaine 40mg (L) and
      placebo (P) were injected submucously in the upper jaw in 12 healthy male
      volunteers who had had cardiovascular diseases excluded. Parameters measured at
      baseline and at 15 minutes, 60 minutes and 105 minutes were systolic blood
      pressure (BP) and heart rate at 50W, 100W and 150W, and cardiac output at 100W.
      Tolerability was assessed by ECG measurements and through reporting of adverse
      events. RESULTS: 15 minutes after drug administration, cardiac output was reduced
      by -3.8% (P), -6.8% (A), and -4.2% (L) [difference between groups was not
      significant]. There were also no statistically significant differences between
      groups for cardiac output at 60 and 105 minutes, or for all BP and heart rate
      measurements. CONCLUSIONS: Neither drug exhibited significant effects on selected
      cardiovascular parameters during submaximal exercise when compared with placebo.

PMID- 17535035
TI  - Lifetime cost-utility analysis of patients with refractory epilepsy treated with
      adjunctive topiramate therapy : cost-effectiveness in refractory epilepsy.
AB  - OBJECTIVE: To evaluate the cost-effectiveness profile of topiramate as adjunctive
      treatment in patients with refractory epilepsy. STUDY DESIGN: Lifetime cost
      utility analysis based on a pharmacoeconomic model. METHODS: Effectiveness data
      (seizure frequency reduction) were derived from the most recent placebo
      controlled clinical trial, whilst quality of life and cost data were retrieved
      from the published literature. Our pharmacoeconomic model was based on a patient
      level approach that incorporated the clinical data of the randomised, controlled
      trial. MAIN OUTCOME MEASURES AND RESULTS: Our analysis showed that chronic
      topiramate treatment costs pound21 353 per quality-adjusted life year (QALY)
      gained (incremental lifetime cost of pound1 024 941 and incremental utility of 48
      QALYs, for every 100 patients) [discounted values with a yearly rate of 3%] (year
      of costing 2001). Sensitivity analyses suggested a range from pound19 915 to
      pound24 518 per QALY gained. CONCLUSIONS: Our results showed that adjunctive
      topiramate therapy has a favourable pharmacoeconomic profile in patients with
      refractory epilepsy.

PMID- 17535036
TI  - Psychomotor and anxiolytic effects of mexazolam in patients with generalised
      anxiety disorder.
AB  - OBJECTIVE: The primary aim of this study was to evaluate the psychomotor effects
      of mexazolam versus placebo in patients with generalised anxiety disorder (GAD).
      PATIENTS AND METHODS: This was a multicentre, randomised, double-blind, parallel
      group clinical trial in 60 outpatients with GAD (Diagnostic and Statistical
      Manual of Mental Disorders-4(th) edition [DSM-IV] criteria). After a placebo run
      in period, patients were assigned to mexazolam 1mg three times daily (n = 32) or
      placebo (n = 28) for 21 days. Effects on psychomotor performance were evaluated
      with the Leeds Psychomotor Test Battery (critical flicker fusion threshold,
      recognition, motor and total reaction time). The Hamilton Anxiety Rating Scale
      (HAM-A) and the Clinical Global Impression (CGI) were used to evaluate the
      patients' clinical status (secondary objective). RESULTS: At neither assessment
      were any statistically significant differences detected between mexazolam and
      placebo for CGI, critical flicker fusion, and the different reaction times. The
      HAM-A total and the HAM-A somatic scores indicated a statistically significant
      therapeutic effect for mexazolam vs placebo after 1 week of treatment but not
      after 3 weeks. The most prominent adverse event with mexazolam was mild
      drowsiness. CONCLUSIONS: Mexazolam in a therapeutically effective dosage regimen
      does not impair psychomotor performance to a clinically relevant extent.

PMID- 17535037
TI  - A Comparison of the Dynamics and Pharmacokinetics of Ropivacaine 7.5 mg/mL with
      and without Epinephrine Used for Epidural Anaesthesia in Urological Surgery.
AB  - OBJECTIVE: To investigate the effects of adding a vasoconstrictor to ropivacaine
      for epidural anaesthesia. PATIENTS AND METHODS: This randomised, double-blind
      study included 44 adults scheduled for urological surgery. Patients received
      either 20mL ropivacaine 7.5 mg/mL (group R, n = 22) or 20mL ropivacaine 7.5 mg/mL
      plus epinephrine 5 mug/mL (group R+E, n = 22) epidurally. Sensory and motor
      blocks were assessed and the pharmacokinetics of ropivacaine determined.
      Haemodynamic responses and adverse events were recorded. Patients were followed
      up for a maximum of 14 days. RESULTS: The groups were similar with respect to
      epidural block characteristics. Only one patient in each group experienced
      inadequate blocks. Median onset of sensory block at surgically relevant
      dermatomes ranged between 5 and 10 minutes in both groups. No significant
      difference in onset time was observed between groups. Median duration of sensory
      block at relevant dermatomes ranged from 3.6 to 5.7h in group R and from 3.3 to
      5.9h in group R+E. Haemodynamic changes were moderate and were not considered
      clinically relevant. The incidence of adverse events was similar between groups.
      Plasma concentrations of ropivacaine peaked around 30 minutes in both groups; the
      mean maximum concentration was slightly higher in group R (1.4 mg/L) than in
      group R+E (1.1 mg/L). CONCLUSIONS: Ropivacaine 7.5 mg/mL with and without
      epinephrine 5 mug/mL produced equally effective and well tolerated epidural
      anaesthesia in urological patients. The addition of epinephrine did not offer any
      pharmacodynamic or pharmacokinetic advantages over ropivacaine alone.

PMID- 17535038
TI  - Effect of Food on the Steady-State Pharmacokinetics of Delavirdine in Patients
      with HIV Infection.
AB  - OBJECTIVE: In a prior single-dose study that examined the effect of food on
      delavirdine pharmacokinetics in healthy volunteers, the absorption of delavirdine
      mesylate was delayed and the area under the curve was reduced by 26% in the
      presence of food. Since the complex, nonlinear pharmacokinetics of delavirdine do
      not permit a simple extrapolation of the results of a single-dose study to steady
      state, the present multiple-dose study was performed. PATIENTS AND STUDY DESIGN:
      Thirteen stable patients with HIV-1 infection (two females, 11 males; CD4 count
      range 124-588 cells/mm(3)) completed a randomised, crossover study in which
      subjects received two 14-day treatments with delavirdine mesylate 400mg every 8
      hours. In treatment A, all delavirdine doses were administered on an empty
      stomach and in treatment B were taken with food. A pharmacokinetic evaluation was
      performed on day 14 of each treatment period. SETTING: An ambulatory AIDS
      research centre in an academic medical centre. INTERVENTIONS: Administration of
      delavirdine with and without food. MAIN OUTCOME MEASURES: Pharmacokinetic
      parameters for delavirdine. RESULTS: The maximum concentration (C(max)) [+/-
      standard deviation] in treatment A was 29.6 +/- 13.6muM and in treatment B it was
      23.0 +/- 8.61muM (p = 0.037). The minimum concentrations (C(min)) were 9.45 +/-
      6.7muM and 11.2 +/- 9.2muM, respectively (p > 0.05). The oral clearances
      (CL(oral)) were 17.8 +/- 41.6 L/h (treatment A) and 18.5 +/- 39.0 L/h (treatment
      B) [p > 0.05]. Similar patterns were observed for N-dealkylated delavirdine with
      a significant difference only in C(max) (4.13 vs 3.47muM [p = 0.022], treatment A
      vs B). CONCLUSIONS: These findings indicated that, in contrast to the increased
      CL(oral) noted in a prior single-dose study, food did not have a significant
      effect at steady state on the area under the plasma concentration-time curve or
      C(min). Although C(max) was significantly lower when the drug was taken taken
      with food, the clinical relevance of this parameter as compared with the trough
      concentration is unclear since the current focus for antiretrovirals is on
      maintaining trough concentrations in excess of in vitro inhibitory
      concentrations.

PMID- 17535039
TI  - Lowest effective single dose of diclofenac for antipyretic and analgesic effects
      in acute febrile sore throat.
AB  - OBJECTIVE: To compare the antipyretic and analgesic effects of a single oral dose
      of diclofenac potassium 6.25, 12.5 or 25mg with paracetamol 1000mg and placebo in
      patients with fever resulting from acute febrile sore throat. DESIGN AND SETTING:
      This was a multicentre, double-blind, double-dummy, randomised, placebo
      controlled, parallel group study conducted at 21 primary-care centres throughout
      France. PATIENTS: In total, 343 adult patients with acute febrile sore throat
      (fever >/=38.0 degrees C) were randomised to the five treatment groups.
      INTERVENTIONS: Patients received one oral dose of medication. Fever, spontaneous
      throat pain and pain on swallowing were recorded over 6 hours. If acute symptoms
      persisted 2 hours after study drug administration, the patient was allowed to
      take rescue medication and discontinue the trial. RESULTS: The antipyretic
      effects of diclofenac potassium 6.25, 12.5 and 25mg and paracetamol 1000mg were
      significantly greater than placebo. The antipyretic effects of diclofenac
      potassium 12.5 and 25mg were numerically greater than paracetamol 1000mg, which
      was comparable to the effect of diclofenac potassium 6.25mg. The analgesic
      effects of the higher doses, diclofenac potassium 12.5 and 25mg, and of
      paracetamol 1000mg were significantly better than placebo. Summary efficacy
      measures over the first 4 hours post-dose showed a dose-response relationship
      among the diclofenac doses, with statistically significant differences on some
      outcomes between the 25mg and the 6.25mg doses. On the global efficacy evaluation
      for relief of fever and throat pain, patients rated both diclofenac potassium
      12.5 and 25mg significantly higher than paracetamol 1000mg (p </= 0.01). In
      contrast, paracetamol 1000mg and diclofenac 6.25mg were not rated significantly
      higher than placebo. Diclofenac potassium was well tolerated, with a safety
      profile comparable to that of placebo, and slightly favourable compared with that
      of paracetamol. CONCLUSIONS: Diclofenac potassium administered as single doses of
      12.5 and 25mg significantly reduced fever and throat pain in patients with acute
      febrile sore throat. The overall efficacy of these doses was rated significantly
      higher than that of paracetamol 1000mg or placebo. A dose-response relationship
      was seen between placebo and the three diclofenac doses. On most outcomes,
      paracetamol 1000mg was similar to or only slightly better than the diclofenac
      potassium 6.25mg dose. Diclofenac potassium 12.5mg is the lowest unit dose that
      could be recommended to provide reliable reduction of oral temperature and relief
      of throat pain.

PMID- 17535040
TI  - Ambroxol lozenge bioavailability : an open-label, two-way crossover study of the
      comparative bioavailability of ambroxol lozenges and commercial tablets in
      healthy thai volunteers.
AB  - OBJECTIVE: To compare the bioavailability of two 15mg ambroxol lozenges with a
      commercial 30mg ambroxol tablet. DESIGN: Open-label, two-way crossover study.
      METHOD: Each formulation was randomly administered to 20 healthy Thai volunteers
      (ten male and ten female) with a 1-week washout period between formulations.
      After administration, serial blood samples were collected over a 24-hour period
      and the plasma concentration of ambroxol was subsequently measured using high
      performance liquid chromatography with ultraviolet detection after liquid-liquid
      extraction. Pharmacokinetic parameters were analysed by a noncompartmental
      pharmacokinetic model and compared between formulations using analysis of
      variance with a significance level of 0.05. RESULTS: The point estimates (90% CI)
      of the area under the plasma concentration-time curve (AUC) and peak plasma
      concentration (C(max)) ratios between lozenge and commercial tablet were 1.07
      (0.89 to 1.28) and 1.20 (1.04 to 1.40), respectively. The point estimate (90% CI)
      of the difference between formulations for time to C(max) was 0.40 (-0.20 to
      1.00). CONCLUSION: The two formulations under test were not bioequivalent based
      on the stipulated bioequivalence criteria. The bioavailability from the ambroxol
      lozenge might be better, since the 90% CI of the AUC(0-infinity) fell outside the
      bioequivalence range, and its range was narrower. The difference in rate of
      absorption was not conclusive because ambroxol was delivered from the lozenge by
      two parallel processes, namely absorption via oral and gastrointestinal mucosa.
      The additional oral mucosal absorption might not only contribute more absorption
      but also introduce variability compared with that of tablet administration. The
      relative importance of oral versus gastrointestinal mucosal absorption of
      ambroxol from the lozenge formulation, and the clinical significance of this,
      requires further study.

PMID- 17535041
TI  - Epstein-barr virus-related post-transplant lymphoproliferative disorder in a
      renal transplant recipient treated with tacrolimus and antithymocyte globulin.

PMID- 17535042
TI  - Fatal cardiogenic shock and liver failure induced by verapamil in a thyrotoxic
      patient.

PMID- 17535044
TI  - Multiple-Dose Pharmacokinetics of Delavirdine Mesylate and Didanosine in HIV
      Infected Patients.
AB  - BACKGROUND: Delavirdine is a non-nucleoside reverse transcriptase inhibitor with
      pH-dependent absorption characteristics that has received accelerated approval
      for the treatment of patients with HIV-1 infection. In a prior single-dose study
      concurrent administration of delavirdine mesylate and didanosine (buffered
      formulation) resulted in up to a 31% decrease in the area under the plasma
      delavirdine concentration versus time curve (AUC) compared with when both drugs
      were taken separately. OBJECTIVE: To evaluate the interaction of these two agents
      at steady state. STUDY DESIGN AND PATIENTS: A total of 11 HIV-infected subjects
      who were previously stabilised on didanosine were enrolled into a randomised,
      open-labelled crossover study. Nine subjects continued to receive their
      prescribed dose and schedule of didanosine, with each dose of didanosine taken
      either together with or 1 hour after delavirdine mesylate (400mg every 8 hours).
      Pharmacokinetic studies at baseline, day 14 and day 28 were conducted and the
      plasma concentrations of delavirdine and didanosine were determined. RESULTS: A
      lower delavirdine maximum plasma concentration (C(max)) [22.4 +/- 11 vs 35.5 +/-
      17muM; p = 0.045] was noted when delavirdine and didanosine were taken together.
      However, no significant difference was noted for delavirdine AUC (114 +/- 56
      muM.h compared with 153 +/- 79 muM.h [p = 0.181]). In addition, no differences
      were noted for didanosine pharmacokinetic parameters between treatments.
      CONCLUSION: These data indicate that patients receiving didanosine and
      delavirdine as part of a combination regimen during long-term therapy can be
      instructed to take them together in an attempt to enhance adherence to treatment
      with both antiretroviral agents.

PMID- 17535045
TI  - Onset and duration of action of ketotifen 0.025% and emedastine 0.05% in seasonal
      allergic conjunctivitis : efficacy after repeated pollen challenges in the vienna
      challenge chamber.
AB  - OBJECTIVE: To compare the efficacy, onset and duration of action, and the safety
      of ketotifen fumarate 0.025% ophthalmic solution and emedastine difumarate 0.05%
      ophthalmic solution in subjects with seasonal allergic conjunctivitis (SAC)
      induced by allergen exposure, using the Vienna Challenge Chamber model. DESIGN
      AND SETTING: This was a double-masked, randomised, comparative, crossover study
      conducted at an allergy outpatient clinic in Austria. STUDY PARTICIPANTS:
      Subjects with an allergy to grass pollen were exposed to the allergen in a pollen
      chamber for 4 hours, followed by a 3-hour break and then a second exposure for 3
      hours. INTERVENTIONS: Study participants were randomised to a treatment sequence
      (ketotifen followed by emedastine or emedastine followed by ketotifen), receiving
      1 drop per eye of ketotifen or emedastine 2 hours after the initial allergen
      exposure in the pollen chamber. OUTCOMES: Individual and composite ocular,
      individual and composite nasal, and total (ocular + nasal) symptom complex scores
      were determined by repeated exposure to allergen 0-2 hours and 5-8 hours after
      dosing. Onset of action was defined as the time to the first observation of a 20%
      reduction from baseline in the composite ocular symptom score. RESULTS: All 37
      subjects enrolled completed the study. The median time to onset of action was 15
      minutes for ketotifen and 30 minutes for emedastine. This difference was
      significant using the generalised linear model (p = 0.048), but not for the log
      rank test analysis. In the initial 2 hours post dose, ketotifen provided
      significantly greater relief of both composite ocular symptoms (p = 0.026) and
      total symptom complex (p = 0.014). Both medications were effective in reducing
      symptoms 5 to 8 hours after dosing. No adverse events were reported for either
      treatment. CONCLUSIONS: In the Vienna Challenge Chamber model, ketotifen and
      emedastine both effectively alleviated ocular symptoms of SAC after single-dose
      administration. Ketotifen had a faster onset of action and provided better
      symptom relief than emedastine during the first 2 hours after dosing. The rapid
      onset of action and symptom control make ketotifen a valuable treatment for SAC.

PMID- 17535043
TI  - Conventional and atypical antipsychotics in the elderly : a review.
AB  - Psychoses are major mental disorders marked by derangement of personality and
      loss of contact with reality, and are common in the elderly. Various hypotheses
      suggest the pivotal role of abnormal neurotransmitter and neuropeptide systems in
      psychotic patients, the most studied of which are the dopaminergic, serotonergic
      and glutamatergic systems. In particular, long-term treatment with antagonists at
      dopamine (D) and serotonin (5-hydroxytryptamine; 5-HT) receptors and agonists at
      glutamate receptors may improve symptoms. Treatment with antipsychotics is very
      common in the elderly and often indispensable. However, for successful treatment
      it is essential to have an adequate multidimensional assessment of the geriatric
      patient and of his or her polypathology and polypharmacy, together with knowledge
      of age-dependent pharmacokinetics and pharmacodynamic changes and drug-drug
      interactions.Conventional antipsychotics such as haloperidol, chlorpromazine,
      promazine, tiapride and zuclopenthixol are D(2)-receptor antagonists and inhibit
      dopaminergic neurotransmission in a dose-related manner. They decrease the
      intensity of all psychotic symptoms, although not necessarily to the same extent
      and with the same time course. Negative symptoms may persist to a much more
      striking extent than delusions, hallucinations and thought disorders, and there
      is a dose-related incidence of extrapyramidal side effects (EPS). Newer
      antipsychotics, such as clozapine, olanzapine, risperidone, quetiapine and
      ziprasidone, have a different receptor-binding profile, interacting with both D
      and 5-HT receptors; they less frequently cause EPS and are better tolerated in
      the elderly. Their use is advantageous because they are effective both on
      positive and negative symptoms of schizophrenia and may also be used in the
      treatment of behavioural disturbances in elderly and/or demented individuals. The
      use of clozapine is limited by the onset of agranulocytosis, whereas olanzapine,
      risperidone, quetiapine and, more recently, ziprasidone are widely used, with
      good results in the above-mentioned diseases.

PMID- 17535046
TI  - One year of Lamivudine therapy for portuguese patients with chronic hepatitis B.
AB  - OBJECTIVE: To assess the efficacy of lamivudine treatment on hepatitis B e
      antigen (HBeAg) and/or hepatitis B surface antigen (HBsAg) seroconversion, on
      other virological and serological markers of response including hepatitis B virus
      (HBV) DNA and serum aminotransferases, and the safety of lamivudine treatment in
      hepatitis B patients. PATIENTS: This phase III open-label study evaluated the
      virological and biochemical response to lamivudine in 70 Portuguese patients with
      HBeAg positive chronic hepatitis B. Patients were treated with lamivudine 100mg
      once daily for 12 months. METHODS: Antiviral activity was assessed by measuring
      alanine aminotransferase (ALT)/aspartate aminotransferase (AST) levels at all
      protocol visits, and hepatitis B serology and HBV DNA were performed at baseline
      and at month 12 visits. Evaluation of safety and tolerance was based on clinical
      adverse events and laboratory analyses. RESULTS: The primary endpoint was
      virological response at month 12, defined as loss of detectable HBeAg from serum
      with a reduction of HBV DNA to undetectable levels, and this was observed in
      19/69 (27.5%) of patients. Almost half of the patients were HBV DNA negative by
      this time. Mean ALT values decreased steadily during treatment and by 12 months
      61% of patients had values within the normal range. HBeAg seroconversion (HBeAg
      negative, HBeAb positive) was achieved in 27.9% of patients by 12 months,
      although all patients remained HBsAg positive. CONCLUSION: Lamivudine was well
      tolerated and the incidence of adverse events was similar to those reported in
      previous studies. Lamivudine treatment resulted in virological and biochemical
      improvements in HBeAg positive chronic hepatitis B patients, with HBeAg
      seroconversion in one-third of patients.

PMID- 17535047
TI  - Wegener's Granulomatosis after Treatment with Montelukast in a Patient not
      Receiving Systemic Corticosteroid Treatment.

PMID- 17535048
TI  - Consensus on drug treatment, definition and diagnosis for insomnia.
AB  - Thirty-four experts and a literature supervisor got together in order to reach a
      'consensus' regarding the definition, diagnosis and pharmacological treatment of
      insomnia. Insomnia is a subjective perception of dissatisfaction with the amount
      and/or quality of sleep. It includes difficulty in initiating or maintaining
      sleep or early awakening with inability to fall asleep again. It is associated
      with complaints of non-restorative sleep and dysfunction of diurnal alertness,
      energy, cognitive function, behaviour or emotional state, with a decrease in
      quality of life. The diagnosis is based on clinical and sleep history, physical
      examination and additional tests, although polysomnography is not routinely
      indicated. Therapy should include treatment of the underlying causes, cognitive
      and behavioural measures and drug treatment. Hypnotic therapy can be prescribed
      from the onset of insomnia and non-benzodiazepine selective agonists of the GABA
      A receptor complex are the drugs of first choice. It is recommended that hypnotic
      treatment be maintained in cases where withdrawal impairs the patient's quality
      of life and when all other therapeutic measures have failed. Experience suggests
      that intermittent treatment is better than continuous therapy. The available data
      do not confirm safety of hypnotics in pregnancy, lactation and childhood
      insomnia. Benzodiazepines are not indicated in decompensated chronic pulmonary
      disease but no significant adverse effects on respiratory function have been
      reported with zolpidem and zopiclone in stable mild to moderate chronic
      obstructive pulmonary disease and in treated obstructive sleep apnoea syndrome.
      Data for zaleplon are inconclusive. If the patient recovers subjective control
      over the sleep process, gradual discontinuation of hypnotic treatment can be
      considered.

PMID- 17535049
TI  - Dermatomycoses of the glabrous skin : a double-blind, randomised, comparative
      trial of sertaconazole 2% cream once daily versus vehicle.
AB  - OBJECTIVE: The aim of this multicentre, double-blind, vehicle-controlled study
      was to investigate the safety and efficacy of once-daily topical application of
      sertaconazole 2% cream compared with corresponding vehicle cream in the treatment
      of patients with tinea of glabrous skin. PATIENTS AND METHODS: A total of 400
      patients were recruited at seven investigational sites; 144 patients in the
      intent-to-treat (ITT) population and 127 in the per-protocol (PP) population were
      treated for 3 weeks with either sertaconazole 2% once daily or corresponding
      vehicle cream. To evaluate therapeutic efficacy and safety, microscopic
      examination of native preparations, mycological cultures, and clinical assessment
      of the state of the lesion (objective and subjective monitoring of symptoms) were
      analysed after 3 weeks of treatment. RESULTS: Based on these parameters, in both
      the PP and ITT populations, sertaconazole cream 2% once daily induced a higher
      cure rate than the vehicle cream: 82% of the PP population (vehicle cream control
      61%; p = 0.014) and 83% of the ITT population (vehicle cream control 59%; p =
      0.003) randomised to sertaconazole with a previously positive mycological culture
      showed negative culture results after sertaconazole treatment. No statistically
      significant differences were observed regarding frequency and severity of adverse
      effects. CONCLUSION: These data indicate that treatment of superficial
      dermatomycoses with sertaconazole 2% cream for 3 weeks is efficient and safe. The
      once-daily application regimen may improve patient compliance, which has been
      shown to be of exceptional importance for successful treatment of dermatomycoses
      of the glabrous skin.

PMID- 17535050
TI  - Randomised, double-blind study of the effects of oxybutynin, tolterodine,
      trospium chloride and placebo on sleep in healthy young volunteers.
AB  - OBJECTIVE: Central nervous effects of oral anticholinergics may limit the success
      of incontinence therapy and patient compliance. Only a few studies investigating
      this topic are available. This study was conducted to determine whether oral
      anticholinergics alter sleep and psychometric test parameters. DESIGN:
      Randomised, double-blind, crossover, placebo-controlled study. STUDY
      PARTICIPANTS: 24 healthy volunteers (age 22-36 years) without sleeprelated
      problems. INTERVENTIONS: Polysomnographic recordings, sleep questionnaires and
      psychometric tests (the number combination test [Zahlen-Verbindungs Test; ZVT]
      and the d2 attention test) were performed following single doses of oxybutynin
      15mg, tolterodine 4mg, trospium chloride 45mg or placebo, each separated by an 8
      day washout period. RESULTS: Rapid eye movement (REM) sleep (relative to total
      sleep time) was the primary parameter of polysomnography. The REM sleep for
      oxybutynin was significantly lower than that for trospium chloride (18.4% vs
      20.2%; p < 0.05) and lower than that for placebo (20.1%; ns). The number
      combination test (ZVT), the primary parameter of cognitive function, and the d2
      test did not reveal any differences in reaction time. With regard to the other
      sleep parameters, the REM latency for oxybutynin was clearly higher than that for
      placebo, trospium chloride and tolterodine. Effects on non-REM sleep were
      observed only after administration of oxybutynin compared with placebo.
      CONCLUSIONS: Oxybutynin influenced sleep structure, as was reflected by REM
      suppression and mild sedation, while subjective parameters and psychometric tests
      remained unaffected. The sleep and psychometric test values for tolterodine and
      trospium chloride were comparable to those of placebo. The clinical relevance of
      these effects is small in healthy young volunteers, but these results cannot be
      extended to the elderly.

PMID- 17535051
TI  - Prevention of nausea and vomiting with ramosetron after total hip replacement.
AB  - OBJECTIVE: Patients undergoing total joint replacement procedures have a
      remarkably high incidence of postoperative nausea and vomiting. The purpose of
      this study was to evaluate the efficacy and safety of ramosetron, a serotonin 5
      HT(3) receptor antagonist, for the prevention of nausea and vomiting after total
      hip replacement. DESIGN: Prospective, randomised, double-blind, placebo
      controlled study. SETTING: University-affiliated teaching hospital. PATIENTS:
      Eighty patients, aged 35-77 years, 22 male and 58 female, scheduled for total hip
      replacement. INTERVENTIONS: Patients received in a randomised, double-blind
      manner intravenously administered placebo or ramosetron in three different doses
      (0.15, 0.3 or 0.6mg) at the completion of surgery (n = 20 in each group). A
      standard general anaesthetic technique and postoperative analgesia were used.
      MAIN OUTCOME MEASURES AND RESULTS: Emetic episodes were recorded and safety
      assessments performed over 0 to 24 hours after anaesthesia. The rate of patients
      experiencing emetic symptoms (nausea, retching, vomiting) over 0 to 24 hours
      after anaesthesia was 70% with ramosetron 0.15mg (p = 0.5), 25% with ramosetron
      0.3mg (p = 0.002) and 20% with ramosetron 0.6mg (p = 0.001), compared with
      placebo (75%). No clinically important adverse events were observed in any of the
      groups. CONCLUSION: Prophylactic antiemetic therapy with ramosetron 0.3mg is
      efficacious against postoperative nausea and vomiting 0 to 24 hours after
      anaesthesia in patients undergoing total hip replacement. Increasing the dose to
      0.6mg provided no further benefit.

PMID- 17535052
TI  - Salivary Flow Rates andPharmacokinetics in Healthy Japaneseand Caucasian
      VolunteersAdministered Oral Pilocarpine : A Comparative Study.

PMID- 17535053
TI  - Antihypertensive efficacy of olmesartan medoxomil and candesartan cilexetil
      assessed by 24-hour ambulatory blood pressure monitoring in patients with
      essential hypertension.
AB  - OBJECTIVE: To compare the antihypertensive efficacy of olmesartan medoxomil with
      that of candesartan cilexetil after 1, 2 and 8 weeks of treatment. DESIGN AND
      SETTING: Randomised, double-blind, parallel-group study conducted at 44 centres
      in Germany, Poland and the Czech Republic. PATIENTS: 643 patients (aged 19-86
      years) with mainly mild-to-moderate essential hypertension received active double
      blind treatment. INTERVENTIONS: Following a 2-week placebo run-in, eligible
      patients were randomly assigned to receive olmesartan medoxomil 20mg (n = 319) or
      candesartan cilexetil 8mg (n = 324) once daily for 8 weeks. MAIN OUTCOME
      MEASURES: Changes from baseline in daytime, 24-hour and night-time diastolic
      (DBP) and systolic (SBP) blood pressures assessed by ambulatory blood pressure
      monitoring (ABPM), and changes from baseline in sitting cuff DBP and SBP.
      RESULTS: Mean decreases from baseline in daytime DBP by ABPM at weeks 1, 2 and 8
      were 6.7, 8.4 and 9.3mm Hg, respectively, in the olmesartan medoxomil group
      compared with 5.3, 6.0 and 7.8mm Hg, respectively, in the candesartan cilexetil
      group. The between-group differences were significantly in favour of olmesartan
      medoxomil at all three timepoints (p </= 0.0126). Significant differences in
      favour of olmesartan medoxomil were also observed for mean 24-hour DBP and for
      mean daytime and 24-hour SBP by ABPM. Decreases from baseline in sitting cuff BP
      at trough were similar in the two groups (15-16mm Hg for DBP and 21mm Hg for
      SBP). Both treatments were well tolerated. CONCLUSIONS: Olmesartan medoxomil
      reduced daytime and 24-hour DBP and SBP, assessed by ABPM, more effectively than
      candesartan cilexetil at the doses tested. The majority of the treatment effect
      in both groups was seen after only 1 or 2 weeks of dosing, when the between-group
      differences were already statistically significant.

PMID- 17535054
TI  - Estimating the long-term visual field consequences of average daily intraocular
      pressure and variance : a clinical trial comparing timolol, latanoprost and
      travoprost.
AB  - OBJECTIVE: To estimate the long-term consequences of average daily intraocular
      pressure (IOP) and variance in patients treated with travoprost, latanoprost or
      timolol. DESIGN AND SETTING: IOP measures were derived from a 12-month
      randomised, double-masked, double-dummy, phase III clinical trial conducted in
      patients with primary open angle glaucoma (POAG) or ocular hypertension. IOP was
      measured at weeks 2, 12, 24 and 48, at 8am, 10am and 4pm. The visual field defect
      (VFD) risk functions estimated by Stewart were applied, the statistical unit
      being the eye. A second-order analysis of variance was performed including eye,
      time, treatment and investigator. Analyses according to baseline IOP were
      performed to identify patients at risk. INTERVENTIONS: IOP-lowering drugs:
      travoprost 0.004% once daily, latanoprost 0.005% once daily and timolol 0.5%
      twice daily. OUTCOME MEASURE: Daily IOP average and variance, and daily minimum
      and maximum IOP and VFD. RESULTS: Travoprost-treated patients (n = 200) had a
      daily IOP average significantly lower than timolol-treated patients (n = 200; p <
      0.0001) and latanoprost-treated patients (n = 196; p < 0.001). Similar results
      were found for daily minimal and maximal IOP values. No difference was found for
      IOP variance between the prostaglandin analogues (p < 0.25), while timolol
      treated patients had a higher value than travoprost-treated patients (p < 0.004).
      Consequently, patients treated with timolol would have a 1.54 greater chance of
      developing a new VFD over 5 years than those using latanoprost. Patients treated
      with latanoprost would have a 1.11 greater chance of developing a new VFD than
      travoprost-treated patients. CONCLUSIONS: Better control of daily IOP average and
      variance should avoid new VFDs. Prostaglandins controlled the variance better
      than timolol, and travoprost was found to be the drug having the most effect on
      IOP average. Longitudinal prospective data collection should be performed to
      confirm these findings.

PMID- 17535056
TI  - Short-Term Oral Diazepam Treatment during Pregnancy : A Population-Based
      Teratological Case-Control Study.
AB  - OBJECTIVE: To study the possible human teratogenicity of short-term (generally 3
      weeks) oral diazepam treatment during pregnancy. DESIGN AND SETTING: A matched
      case-population control pair analysis based on the total (maternal self-reported
      and medically recorded) or medically recorded diazepam treatments, in addition to
      a comparison between cases and patient controls in the population-based large
      data set of the Hungarian Case-Control Surveillance of Congenital Abnormalities
      from 1980 to 1996. STUDY PARTICIPANTS: 38 151 population-control neonates without
      any congenital abnormalities, 22 865 neonates or fetuses with congenital
      abnormalities (cases) and 812 neonates or fetuses with Down's syndrome (patient
      controls). MAIN OUTCOME MEASURES: 24 congenital abnormality groups. RESULTS: 2746
      (12.0%) cases, 4130 (10.8%) population controls and 97 (11.9%) patient controls
      were born to mothers treated with diazepam during pregnancy. The matched case
      population control pair analysis showed a higher rate of limb deficiencies,
      rectal-anal atresia/stenosis, cardiovascular malformations and multiple
      congenital abnormalities after diazepam use during the second and third months of
      gestation, i.e. in the critical period for most major congenital abnormalities,
      based on maternal self-reported and medically recorded information. However, the
      evaluation of only medically recorded diazepam use did not indicate a higher use
      of diazepam in any congenital abnormality group. Thus, the higher occurrence of
      diazepam treatment among cases in the primary analysis may be due to the lower
      proportion of maternal self-reported diazepam intake in the population control
      group, i.e. recall bias. The comparison of diazepam use between 24 congenital
      abnormality groups and patient controls as the referent group showed a difference
      only in the group of intestinal atresia/stenosis, probably due to chance error
      caused by multiple comparison. CONCLUSIONS: Short-term diazepam treatment in
      usual therapeutic doses during pregnancy did not present any detectable
      teratogenic risk to the fetus.

PMID- 17535055
TI  - Speed of recovery from acute exacerbations of chronic obstructive pulmonary
      disease after treatment with antimicrobials : results of a two-year study.
AB  - OBJECTIVE: We performed a multicentre study under a 2-year observational protocol
      that included data on time to recovery from acute exacerbations of chronic
      obstructive pulmonary disease (AE-COPD) in patients receiving moxifloxacin and
      comparator antimicrobials. PATIENTS AND METHODS: Outpatients with moderate or
      severe COPD were recruited from respiratory clinics throughout Spain.
      Moxifloxacin was available in year 2, and was to be prescribed to 50% of patients
      in that period in a non-randomised allocation. Time to recovery was compared in
      successfully treated AE-COPD; cross-sectionally for all AE-COPD over 2 years,
      first AE-COPD and all AE-COPD in year 2, and longitudinally in patients receiving
      comparator antimicrobials for AE-COPD in year 1 and moxifloxacin in year 2.
      RESULTS: 614 AE-COPD were treated in 441 patients over 2 years (mean age 66.7 +/-
      8.3 years, 98% males, mean forced expiratory volume in 1 second [FEV(1)] 35.9 +/-
      8.8%). Mean time to recovery overall was 4.6 days (SD 3.3) with moxifloxacin 400
      mg/day for 5 days, and 5.8 days (SD 4.6) with comparators (p < 0.01), which were
      most frequently amoxicillin/clavulanic acid 500/125mg/8h, clarithromycin
      500mg/12h and cefuroxime axetil 500mg/12h for 7-10 days. Longitudinal analysis
      showed that 27 patients treated with moxifloxacin in the second year of the study
      recovered in a mean of 3.7 days (SD 3.1), and the same patients treated with
      comparator antimicrobials in year one recovered in a mean of 6.8 days (SD 4.6) [p
      = 0.02]. In contrast, in 66 patients treated with comparator antimicrobials in
      both years, mean time to recovery was 7.4 days (SD 7.3) in year one and 5.5 days
      (SD 3.5) in year two (p = 0.24). All subgroup analyses showed a statistically
      significant reduction of 18-25% in time to recovery with moxifloxacin compared
      with other antibiotics. CONCLUSIONS: Moxifloxacin significantly reduced time to
      recovery from AE-COPD in patients with moderate to severe disease by
      approximately 20% (>1 day) compared with other antimicrobials. Faster recovery
      should result in earlier return to work or normal activities, and to social and
      economic savings.

PMID- 17535057
TI  - Serum Rifampicin Levels in Patients with Tuberculosis : Effect of P-Glycoprotein
      and CYP3A4 Blockers on its Absorption.
AB  - OBJECTIVE: To identify patients with tuberculosis (TB) showing poor
      bioavailability for rifampicin and to delineate the role of possible factors such
      as overexpression of intestinal cytochrome P450 3A4 (CYP3A4) and P-glycoprotein
      (PGP) in the drug's bioavailability by administering known blockers. PATIENTS,
      DESIGN AND SETTING: 77 clinically proven TB patients were included in this
      nonblinded, randomised, comparative trial carried out at one centre at the All
      India Institute of Medical Sciences, New Delhi, India. INTERVENTIONS: The
      concentrations of rifampicin and its active metabolite, 25-desacetylrifampicin
      (DRMP), were measured in blood samples of the 77 TB patients at 0, 1, 2 and 4
      hours after their usual morning rifampicin dose. Of these, 19 patients showing
      the lowest area under the concentration-time curve values from 0 to 4 hours after
      administration (AUC(0-4)) were selected and pretreated with a single dose of
      either verapamil (80mg) or itraconazole (200mg) as both PGP and CYP3A4 blockers 1
      hour prior to rifampicin administration. Rifampicin and DRMP concentrations were
      estimated using high performance liquid chromatography in all serum samples
      collected at the same timepoints. MAIN OUTCOME MEASURES AND RESULTS: A
      statistically significant increase (p < 0.05) was found both in the serum levels
      of rifampicin at 2 hours and in the AUC(0-4)values (158% and 84%, respectively)
      after pretreatment with verapamil. However, an increase in the levels of
      rifampicin was found to be insignificant on pretreatment with itraconazole. The
      estimated levels of DRMP also supported these results. CONCLUSIONS: The increase
      in rifampicin levels on administration of a PGP/CYP3A4 blocker suggests a pivotal
      role for PGP/CYP3A4 in the absorption of rifampicin in patients with TB, which
      may be responsible for lower or variable levels of rifampicin.

PMID- 17535058
TI  - A Comparison of the Therapeutic Plan Costs in the Treatment of HIV-Positive
      Patients.
AB  - OBJECTIVE: To determine the cost of each therapeutic protocol (TP) used for HIV
      positive patients and to identify the most frequently adopted one by relating it
      to the cost and by identifying the drug (drugs) that is more competitive in
      relation to expense. SETTING: Infectious Disease Department and Hospital
      Pharmacy, Ospedale Maggiore, Bologna, Italy. The department treats approximately
      600 outpatients with HIV infection each year. PATIENTS AND METHODS: 464 patients
      with HIV infection were examined every 3 months and clinicians judged whether the
      treatment (usually consisting of three drugs) was to be continued or changed
      according to its effectiveness, availability and possible new treatment options.
      The study also ascertained the cost of antiretroviral drugs within the period 1
      January 2001-30 April 2002, and identified the most commonly used therapeutic
      protocols, the relevant daily cost and the frequency of use in all patients. The
      cost of the various protocols (most TPs were grouped in the most frequently used
      15 regimens) was considered only at the end of the study, in order to define the
      percentage differences in cost. Importantly, from the beginning, this aspect was
      not a primary factor in drug choice. RESULTS: The antiretroviral drug cost was 4
      448 186 Euro (euro) in 2001 and euro1 536 984 in the first 4 months of 2002, with
      an increase of 3.5% compared with the same period in 2001. In the 16 months under
      consideration, 55.21% of the cost was associated with nucleoside reverse
      transcriptase inhibitors (NRTI), 25.97% with protease inhibitors (PI) and 18.83%
      with non-nucleoside reverse transcriptase inhibitors (NNRTI). Among the 464 TPs
      considered, 331 (71.33%) were distributed among 15 prevalent TPs. The least
      expensive TP (euro9.95/day; time of costing 1 January 2001-30 April 2002)
      comprised two drugs (stavudine and lamivudine) and showed a cost differential of
      +euro16.74 (+62.70%) compared with the most expensive one (zidovudine,
      lamivudine, lopinavir and ritonavir). The most used TP (zidovudine, lamivudine
      and nevirapine) covered 61 cases (13.1%) with a daily cost of euro19.61 (time of
      costing 1 January 2001-30 April 2002). CONCLUSIONS: This study demonstrated that,
      starting with decisions that take into account the efficacy of the therapy and
      the compliance of the patients, and choosing ethical protocols agreed upon with
      the patients, it is possible to reduce the costs of the TPs. Of the 464 TPs
      examined, NNRTIs were used in 46.7% of the cases and a PI in 39.6% (16.1% of the
      latter drug group was boosted with ritonavir). Only 7% of TPs used two drugs
      (NRTIs). The two less expensive TPs comprised two drugs only (NRTIs). Among the
      three-drug TPs with a lower cost, the drug pattern was two NRTIs and one NNRTI.
      The remaining TPs included a PI as a third drug and demonstrated a cost increase
      greater than 50% with respect to the less expensive treatment.

PMID- 17535059
TI  - Isoniazid overdose : a case series, literature review and survey of antidote
      availability.
AB  - Tuberculosis has re-emerged as a significant public health threat over the last
      decade both globally and within Australia. This is thought to be largely due to
      the HIV epidemic, a growing itinerant population, and immigration. The antibiotic
      isoniazid remains an integral part of drug therapy. With the numbers of patients
      receiving isoniazid remaining high, the number of cases of acute poisoning is
      expected to be significant. This paper presents a series of two cases of
      isoniazid poisoning presenting to a tertiary referral centre in North Queensland.
      Isoniazid toxicity produces a triad of coma, metabolic acidosis and seizures. The
      seizures are often refractory to traditional antiepileptics. A specific antidote
      is available (pyridoxine [vitamin B6]) and both patients were administered this
      as part of their treatment. We also surveyed all hospitals in Australia with an
      accredited adult Emergency Department to assess the availability of pyridoxine.

PMID- 17535060
TI  - Severe psoriasis palmaris et plantaris associated with topical use of
      dorzolamide.

PMID- 17535062
TI  - Pharmacokinetic evaluation of rofecoxib : comparison of tablet and suspension
      formulations.
AB  - OBJECTIVE: Rofecoxib suspension is a formulation developed to increase the
      convenience of rofecoxib therapy for patients who have difficulty swallowing
      tablets. This open-label, two-part study compared the single-dose
      pharmacokinetics of rofecoxib tablets and rofecoxib suspension in healthy
      subjects. DESIGN AND STUDY PARTICIPANTS: Part I was a two-period crossover study
      that assessed the bioequivalence of the 12.5mg/5mL rofecoxib suspension and the
      12.5mg rofecoxib tablet in 24 healthy subjects (12 men and 12 women). Part II was
      a crossover study in 24 additional healthy subjects (12 men and 12 women) that
      determined the bioequivalence of the rofecoxib 25mg/5mL suspension and the 25mg
      rofecoxib tablet. RESULTS: No clinically meaningful differences between rofecoxib
      tablet and suspension were apparent with respect to the rofecoxib area under the
      concentration-time curve from time zero to infinity (AUC(0-infinity)) and maximum
      plasma concentration (C(max)), the primary measures of bioequivalence. At the
      12.5mg and 25mg doses, the 90% CI for the geometric mean ratio
      (suspension/tablet) of both AUC(0-infinity) and C(max) fell within the
      prespecified interval for bioequivalence (0.80-1.25). CONCLUSIONS: The rofecoxib
      suspension is bioequivalent to the rofecoxib tablet at single oral doses of
      12.5mg and 25mg in healthy volunteers. The convenience and ease of administration
      of rofecoxib suspension may translate into increased compliance with therapy
      compared with a conventional solid tablet formulation, particularly for elderly
      patients.

PMID- 17535061
TI  - Comparison of Clarithromycin and Amoxicillin/Clavulanic Acid for Community
      Acquired Pneumonia in an Era of Drug-Resistant Streptococcus pneumoniae.
AB  - OBJECTIVE: To compare the safety and efficacy of clarithromycin and
      amoxicillin/clavulanic acid in patients with community-acquired pneumonia due to
      penicillin-resistant and/or macrolide-resistant Streptococcus pneumoniae, by
      selecting clinical investigators who practice in study populations from
      geographic areas in which a high incidence of resistant strains is reported by
      surveillance. DESIGN AND SETTING: Prospective, randomised, investigator-blinded,
      multicentre study conducted in 45 sites in primary-care and referral centre
      settings. PATIENTS AND INTERVENTIONS: 327 ambulatory patients diagnosed with
      radio-graphically confirmed community-acquired pneumonia administered
      clarithromycin 500mg immediate-release or amoxicillin/clavulanic acid 875mg/125mg
      twice daily for 7 days. MAIN OUTCOME MEASURES AND RESULTS: Similarly high
      clinical cure rates were observed among evaluable patients in both treatment
      groups at the test-of-cure visit (28-35 days post-treatment): 92% (114/124) for
      clarithromycin and 91% (117/129) for amoxicillin/clavulanic acid. Of 85 S.
      pneumoniae strains isolated pretreatment, four (5%) were classified as resistant
      to macrolides (one mefA, two ermB, and one ermB + mefA) and eight (9%) had
      reduced susceptibility to penicillin. The overall eradication rate for pathogens
      isolated from bacteriologically and clinically evaluable patients was 91% for
      clarithromycin and 93% for amoxicillin/clavulanic acid, and 89% and 92%,
      respectively, for S. pneumoniae strains. The rates of resolution and/or
      improvement in clinical signs and symptoms and radiological improvement were
      similar with clarithromycin to those with amoxicillin/clavulanic acid, as was
      overall incidence of adverse events. CONCLUSION: A 7-day course of clarithromycin
      immediate-release was similar to amoxicillin/clavulanic acid based on high rates
      (>90%) of clinical cure, radiological improvement and pathogen eradication among
      ambulatory-care patients with community-acquired pneumonia. As the resistance
      rate at baseline was low, no conclusion could be made about clarithromycin's
      efficacy for infections caused by macrolide-resistant S. pneumoniae. Both
      treatments were well tolerated.

PMID- 17535063
TI  - Quality-of-Life Measurements in Juvenile Rheumatoid Arthritis Patients Treated
      with Etanercept.
AB  - OBJECTIVE: The aims of this study were: (1) to assess functional status,
      emotional well-being and quality of life in patients with polyarticular and
      systemic juvenile rheumatoid arthritis (JRA) treated with etanercept, and (2) to
      determine the prevalence and significance of adverse events associated with
      etanercept therapy. PATIENTS AND METHODS: All JRA patients (n = 21) who received
      etanercept in our rheumatology clinic over a 14-month period were evaluated.
      Patient demo-graphics, type of arthritis, dosing regimens, family history,
      measures of joint function and laboratory parameters were obtained for each
      patient. A questionnaire that comprised validated functional assessment and
      quality-of-life measures (the Childhood Health Assessment Questionnaire
      [CHAQtrade mark], the Juvenile Arthritis Function Assessment Report [JAFAR 5trade
      mark] and the Pediatric Quality of Life Inventory Version 4 [PedsQL Generic
      Scaletrade mark] scales) was administered to patients and parents to assess
      physical and emotional function, pain, adverse drug events and quality of life at
      each clinic visit. RESULTS: Functional status and quality of life improved in
      patients with poly-articular and systemic disease. A significant difference
      between pre- and post-etanercept functional assessment (JAFARtrade mark and
      CHAQtrade mark) and quality-of-life assessment by parents and patients was found
      (p = 0.009, p = 0.002, p </= 0.001, p </= 0.001, respectively). The JAFARtrade
      mark results concurred with those of the CHAQtrade mark test, and did not
      distinguish between patients with polyarticular and systemic disease. Laboratory
      parameters indicative of toxicity did not differ between patients with
      polyarticular and systemic JRA and the number of adverse events reported was low.
      Underlying disease did not appear to predict improvement. CONCLUSION: Etanercept
      appeared to improve functional status, emotional well-being, quality of life and
      activity level with minimal toxicity in patients with polyarticular and systemic
      JRA.

PMID- 17535064
TI  - Intramuscular Dipyrone versus Oral Ibuprofen or Nimesulide for Reduction of Fever
      in the Outpatient Setting.
AB  - OBJECTIVE: To compare the effectiveness and rate of temperature reduction of
      three antipyretic medications in febrile children. DESIGN: A single-dose,
      randomised, prospective, modified double-blind, parallel clinical trial. SETTING:
      The paediatric emergency department of a university hospital that has 13 000
      annual visits. STUDY PARTICIPANTS: 252 otherwise healthy children aged 6 months
      to 14 years with acute, intercurrent, febrile illness. INTERVENTIONS: Enrolled
      children were assigned to receive a single dose of oral ibuprofen 10 mg/kg, oral
      nimesulide 2.5 mg/kg, or parenteral dipyrone 10 mg/kg. MAIN OUTCOME MEASURES AND
      RESULTS: Axillary temperature was measured at the time of antipyretic
      administration and at 30, 45, 60 and 120 minutes thereafter. All three
      medications were effective in reducing the axillary temperature during the 2-hour
      testing period. The rates of axillary temperature change between the three
      medications were significantly different for the ibuprofen and dipyrone groups (p
      = 0.023). In addition, the axillary temperature in the dipyrone group was
      significantly lower than that in the ibuprofen group (p = 0.036) at 120 minutes.
      There was no significant difference in antipyretic effect between the nimesulide
      group and the other two groups during the testing period. Within each group the
      difference between initial temperature and the temperature at the end of the
      testing period was statistically significant (p = 0.036) for the dipyrone group
      only. CONCLUSIONS: All three antipyretic medications were effective in reducing
      the axillary temperature in febrile children. Although administration of
      intramuscular dipyrone seemed to be more effective than ibuprofen, this
      relationship was not significant when nimesulide was considered. In addition, in
      view of its known side effects and the problems associated with intramuscular
      administration in children, the preference for orally administered nimesulide or
      ibuprofen over dipyrone in the setting of the emergency department seems more
      logical provided that the child accepts oral therapy.

PMID- 17535065
TI  - Association of polycystic ovaries with the use of valproic Acid in jordanian
      epileptic patients.
AB  - OBJECTIVE: To investigate the frequency of occurrence of polycystic ovaries (PCO)
      in women taking valproic acid (VPA) as monotherapy for epilepsy. STUDY DESIGN AND
      PATIENTS: 163 epileptic patients were seen at the outpatient neurology clinic at
      Princess's Basma Teaching Hospital, Irbid, and Basheer Hospital, Amman, Jordan. A
      detailed medical history was taken from the patients followed by a clinical
      examination and vaginal ultrasonography of the ovaries. RESULTS: 102 patients
      (62.5%) had primary generalised seizures, 46 patients (28.2%) had partial
      seizures and 15 patients (9.2%) had partial secondary generalised seizures. Mean
      age +/- standard error of the mean (SEM) was 29.8 +/- 0.97 years. The duration of
      epilepsy and treatment with VPA were (mean +/- SD) 9.1 +/- 0.48 and 7.9 +/- 0.4
      years, respectively. The dose and serum concentrations of VPA were (mean +/- SD)
      983.9 +/- 101.96mg and 52.7 +/- 4.7 mg/L, respectively. Mean body mass index
      (BMI) was 25.6 +/- 0.92 kg/m(2). The mean weight gain was 6.6 +/- 1.3kg (range 2
      24kg). Menstrual abnormalities were detected in 58 (35.6%) patients. Twelve
      patients (7.4%) had PCO; these patients were compared with 17 patients without
      PCO selected randomly. There was a statistically significant difference in
      testosterone level and BMI values in patients with PCO compared with those
      without negative PCO. Patients with PCO had a mean +/- SEM serum testosterone
      level of 1.2 +/- 0.18 mug/L and BMI values of 29.24 +/- 1.75 kg/m(2). However,
      patients without PCO had a serum testosterone level of 0.61 +/- 0.1 mug/L and a
      BMI of 21.91 +/- 0.7 kg/m(2). Menstrual abnormalities were detected in all
      patients with PCO and in eight patients without PCO. Hirsutism was found in four
      cases with PCO and in one case with no PCO. There were no statistically
      significant differences in the duration of therapy, doses and serum
      concentrations of VPA in patients with PCO compared with those without PCO.
      CONCLUSION: These results suggest an association between the use of VPA and PCO,
      hyperandrogenism, obesity and menstrual abnormalities. For women receiving VPA
      therapy, clinicians should consider performing an assessment of ovarian structure
      and function, especially if these patients develop menstrual cycle disturbances
      during treatment.

PMID- 17535067
TI  - Candesartan cilexetil in haemodialysis patients.
AB  - OBJECTIVE: Intermittent activation of the renin-angiotensin system during
      dialysis may be related to the high risk of cardiovascular disease in dialysis
      patients. The aim of the present study was to investigate the pharmacokinetics
      and short-term tolerability of the angiotensin II type 1 receptor antagonist
      candesartan cilexetil in patients receiving chronic haemodialysis. DESIGN: The
      study was a double-blind, randomised, placebo-controlled, dose-escalation study.
      Candesartan cilexetil was administered once daily, starting at 4mg with up
      titration biweekly to 8mg and 16mg, respectively. Trough plasma concentrations of
      candesartan were determined before dialysis. After 2 weeks on the highest dose,
      plasma concentrations were obtained at frequent intervals after dose
      administration. PATIENTS: Twenty patients receiving chronic haemodialysis and
      with adequately controlled blood pressure were included in the study. Fourteen
      patients were randomised to candesartan cilexetil and six to placebo. RESULTS:
      Nine of the patients randomised to candesartan cilexitil reached the maximum dose
      of 16mg and completed the study according to protocol. Their blood pressure
      remained stable. Four patients discontinued active treatment due to hypotension
      at the lowest dose. Trough plasma concentrations of candesartan determined at the
      end of each study period increased linearly with dose. Following administration
      of candesartan cilexetil 16mg the maximum plasma concentration of candesartan was
      244 +/- 54 mug/L and the area under the concentration-time curve over 24 hours,
      i.e. one dosing interval (AUC(tau)), was 2767 +/- 1162 mug/L . h. CONCLUSION:
      Steady-state plasma concentrations of candesartan were approximately twice as
      high in haemodialysis patients as in subjects with normal renal function.
      Provided blood pressure is carefully monitored, candesartan cilexetil can be
      titrated from 4mg up to 16mg once daily in haemodialysis patients.

PMID- 17535066
TI  - Pharmacokinetics and pharmacodynamics of intramuscular dermatan sulfate revisited
      : a single- and repeated-dose study in healthy volunteers.
AB  - OBJECTIVE: To assess the pharmacokinetics and effects on blood coagulation of
      dermatan sulfate (DS), a glycosaminoglycan with antithrombotic properties,
      following intravenous and single and repeated intramuscular administrations. The
      mean molecular weight of DS is currently 22kD, i.e. 5kD lower than batches used
      in the early development of the compound. SUBJECTS AND METHODS: Each of 14 male
      healthy volunteers received DS 300mg as an 8-hour intravenous infusion and as
      single and repeated (once daily for 9 days) intramuscular injections. Nine of the
      same subjects were also given DS 100mg and 200mg as single intramuscular doses.
      Plasma DS concentrations were measured with a specific chromogenic assay.
      Activated partial thromboplastin time (aPTT) and thrombin clotting time (TCT)
      responses were also determined. RESULTS: The mean +/- SD volume of distribution
      and terminal half-life of DS were 6.0 +/- 1.4L and 0.9 +/- 0.2h after intravenous
      infusion. Maximum plasma concentration (C(max)) and area under the plasma
      concentration-time curve after single intramuscular injections were dose
      proportional. After repeated intramuscular administration, steady state was
      reached by day 3. On day 9, plasma DS fluctuated between 4.3 +/- 1.5 (C(max)) and
      0.9 +/- 0.4 (minimum plasma concentration at steady state) mg/L, time to C(max)
      was 3.4 +/- 0.8h, terminal half-life was 12.2 +/- 4.1h and the accumulation
      factor was 2.0 +/- 0.5. Geometric mean bioavailability of intramuscular DS was
      54% and 79% after single and repeated 300mg administration, respectively. aPTT
      and TCT responses were both linearly related to plasma DS concentrations, with
      TCT showing greater responsivity. CONCLUSION: As compared with earlier DS
      studies, the present data showed a greater extent of DS absorption after single
      intramuscular administration and a faster absorption rate after repeated dosing,
      and provided evidence of dose-response predictability. These findings may explain
      the improved antithrombotic efficacy of DS observed in a recent clinical trial.

PMID- 17535068
TI  - Dose and Frequency of Administration of Interferon-beta Affect its Efficacy in
      Multiple Sclerosis.
AB  - Data reviewed in this article demonstrate that both interferon-beta-1a (IFNbeta
      1a) and interferon-beta-1b (IFNbeta-1b) show a dose-response relationship in
      multiple sclerosis at current clinical doses. Moreover, the efficacy of these
      therapies is probably dependent on their frequent administration to maintain
      optimal levels of biological effect. These results differ from the conclusions of
      a recent review of data comparing two doses of IFNbeta-1a, given intramuscularly
      once weekly, that showed no difference in efficacy between the two doses. This
      and other results were interpreted to indicate that the current dose of this
      product (30microg intramuscularly once weekly) is optimal. However, the data
      reviewed here indicate that the efficacy of IFNbeta differs depending on the
      features of the dose regimen, including total dose, route and frequency of
      administration. Direct comparative data indicate that 44microg given
      subcutaneously three times weekly is more effective on clinical and magnetic
      resonance imaging measures, at least up to 48 weeks of therapy, compared with
      30microg intramuscularly once weekly; risk-benefit favours 44mug three times
      weekly over 30mug once weekly.

PMID- 17535069
TI  - Clinical benefits with oseltamivir in treating influenza in adult populations :
      results of a pooled and subgroup analysis.
AB  - BACKGROUND: Influenza is a potentially life-threatening illness that affects
      approximately 10% of the population annually, with resulting personal misery and
      societal disruption. Oseltamivir is a novel influenza treatment that has been
      extensively investigated. We describe a series of retrospective analyses
      investigating various measures of clinical efficacy across different populations
      of influenza-infected patients enrolled in studies of oseltamivir (Tamiflu((R)))
      that were conducted within the clinical development programme. METHODS:
      Adolescents and adults (13-97 years, n = 4015) presenting within 36 hours of
      onset of influenza symptoms were randomised to receive oseltamivir 75mg or
      placebo twice daily for 5 days during local influenza outbreaks. Of these
      patients, 2413 had laboratory-confirmed influenza and are included in the
      analysis. Approximately 30% (n = 739) of patients were 'high risk'; 20% were
      healthy elderly subjects (n = 488) and 10% (n = 251) were patients with chronic
      respiratory and/or cardiac conditions. The primary endpoint was time to
      alleviation of a seven-symptom cluster in influenza-infected patients.
      Supplementary analyses were conducted using a variety of illness definitions and
      symptom clusters to investigate the sensitivity of the assessment of overall
      efficacy to differing disease definitions and also to explore efficacy in
      important subpopulations. RESULTS: A total of 2413 patients had confirmed
      influenza infection (placebo: n = 1063; oseltamivir: n = 1350). Across all
      populations, the time to alleviation of illness was reduced by 19% (median
      duration 100.6 hours [95% CI 94.8-104.7]) compared with placebo (124.5 hours [95%
      CI 117.7-132.3], p < 0.0001). Oseltamivir recipients returned to normal health
      status, regained ability to perform usual activities and regained normal sleep
      patterns significantly faster than placebo recipients. The median duration of
      troublesome influenza symptoms was significantly reduced by oseltamivir
      treatment, e.g. fatigue by 29% and myalgia by 26% (both p < 0.0001). After 48
      hours of treatment, 57% more placebo than oseltamivir recipients remained
      febrile, despite greater use of acetaminophen by placebo recipients. In addition,
      the median duration of acute febrile illness was significantly shortened by
      oseltamivir treatment compared with placebo in patients with cardiac disease
      (44.0 hours vs 64.7 hours, p = 0.026) or chronic obstructive airways disease
      (37.9 hours vs 53.8 hours, p = 0.004).Efficacy was similar among influenza A- and
      influenza B-infected patients. Oseltamivir was well tolerated, with transient
      gastrointestinal effects (observed in one in seven oseltamivir-treated patients
      compared with one in 12 patients on placebo) that only rarely resulted in study
      discontinuation. CONCLUSIONS: Oral oseltamivir is a well tolerated and effective
      treatment for influenza in adolescents and adults, including the elderly and
      patients with chronic cardiac and/or respiratory disease.

PMID- 17535070
TI  - Long-Term Cost Effectiveness of Interferon-beta-1a in the Treatment of Relapsing
      Remitting Multiple Sclerosis : An Econometric Model.
AB  - OBJECTIVE: To evaluate the cost effectiveness of subcutaneous interferon-beta-1a
      (IFNbeta-1a) 44mug three times weekly in relapsing-remitting multiple sclerosis
      (RRMS) using an econometric model. METHODS: Data on RRMS patients treated with
      IFNbeta-1a 22 or 44mug subcutaneously three times weekly or placebo for up to 4
      years were obtained from the Prevention of Relapses and disability by Interferon
      beta-1a Subcutaneously in Multiple Sclerosis (PRISMS) study. The area under the
      Expanded Disability Status Scale (EDSS) score-time curve was used as a measure of
      disability and the effectiveness of therapy was expressed as EDSS-months of
      disability prevented. Costs were calculated for the UK and France, and results
      were projected to 10 and 20 years using a time series regression model. RESULTS:
      Over 10 years, treatment with IFNbeta-1a 44mug subcutaneously three times weekly
      prevented 121 EDSS-months of additional disability at a cost of Euros (euro)732
      each (year of costing 2000). Over 20 years, 321 EDSS-months were saved at a cost
      of euro359 per month (year of costing 2000). CONCLUSION: This analysis indicated
      that IFNbeta-1a 44mug subcutaneously three times weekly is cost effective in RRMS
      and that treatment becomes increasingly cost effective over time.

PMID- 17535071
TI  - Managing hypertension with combination diuretics and methyldopa in nigerian
      blacks at the primary care level.
AB  - OBJECTIVE: To gain insight into the control of hypertension and to suggest
      possible interventions within a selected black population treated with
      combination diuretics (amiloride 5mg + hydrochlorothiazide 50mg) and/or
      methyldopa for uncomplicated essential hypertension. DESIGN AND SETTING: A 2-year
      retrospective cohort review of the outpatient medical records of a State
      Comprehensive Health Center in southwestern Nigeria. Free primary health service,
      including free drugs, is provided in the health facility for all patients.
      PATIENTS AND METHODS: The study population included outpatients continuously
      registered at the health centre between June 1999 and June 2002, aged >/=36
      years, with 2-6 months' history of hypertension or newly diagnosed hypertension
      and followed for 6 months after diagnosis. They were managed with methyldopa
      250mg and/or combination diuretics (amiloride 5mg + hydrochlorothiazide 50mg) or
      a combination in two different regimens for at least 6 months. Participating
      physicians measured patients' blood pressure with a validated device and recorded
      demographics and medical history. Patients were considered to have hypertension
      if systolic blood pressure was >140mm Hg and diastolic blood pressure was >90mm
      Hg. RESULTS: Bivariate regression analysis revealed that systolic blood pressure
      contributed moderately to the variances of drug and regimen decisions. Among the
      128 hypertensive patients with average and modal ages of 57.2 +/- 11.1 and 60
      years, respectively, only 37.5% had controlled blood pressure after the first
      treatment; with 10.2% and 4% of the study population needing, respectively, three
      and five re-treatments within 6 months to achieve target blood pressure levels.
      CONCLUSION: A high percentage of uncontrolled blood pressure and re-treatment
      rates were observed within the study population. A more aggressive management
      strategy that individualises diuretic therapy by titrating dose to systolic blood
      pressure and prioritises lifestyle modification in middle-aged and elderly black
      hypertensive patients is suggested.

PMID- 17535072
TI  - Efficacy of pefloxacin in the treatment of patients with acute infectious
      diarrhoea.
AB  - OBJECTIVE: To investigate the clinical and bacteriological efficacy of 5- and 7
      day pefloxacin therapy in patients with acute infectious diarrhoea. PATIENTS AND
      STUDY DESIGN: Eighty-two adult patients with acute infectious diarrhoea were
      randomly divided into three groups: group 1 (n = 20) received 5 days of treatment
      with pefloxacin, group 2 (n = 27) was assigned to a 7-day pefloxacin protocol,
      and group 3 (n = 35) was treated symptomatically. The daily dose of pefloxacin
      was 400mg orally. Clinical and bacteriological response was analysed on the
      third, fifth and seventh days of treatment as well as 1 and 4 weeks after the end
      of treatment. The study was an open-labelled, prospective clinical trial.
      RESULTS: In the 47 patients (100%) of both pefloxacin groups a clinical
      improvement was noted on the third day compared with the control group, where
      this occurred on day 7. Bacteriological eradication was verified on the fifth day
      in 18 patients (90%) from group 1 and in 25 patients (93%) from group 2; they all
      had negative stool cultures 1 and 4 weeks after therapy was completed. Only 22
      patients (63%) in the control group had negative stool cultures on the seventh
      day of treatment, but 4 weeks later all of them were negative. CONCLUSION: There
      was no difference in clinical (p = 0.232) and bacteriological (p = 0.972)
      efficacy between the 5- and 7-day pefloxacin treatment protocols. However, both
      protocols differed significantly in clinical improvement (p < 0.001) and
      bacteriological eradication (p = 0.017) from the control group.

PMID- 17535073
TI  - Efficacy and safety of ketotifen eye drops as adjunctive therapy to mometasone
      nasal spray in subjects with seasonal allergic rhinoconjunctivitis.
AB  - OBJECTIVE: To compare the efficacy and safety of ketotifen 0.025% ophthalmic
      solution (one drop/eye) with placebo as adjunctive therapy to mometasone nasal
      spray (50 microg/spray, two puffs/nostril) in subjects with seasonal allergic
      rhinoconjunctivitis (SARC). STUDY DESIGN: Single-centre, randomised, double
      masked, two-treatment, two-period crossover study. SETTING: 8-hour allergen
      challenge in the Vienna Challenge Chamber. STUDY PARTICIPANTS: Subjects were
      >/=18 years old, had a >/=2-year history of SARC, and were sufficiently
      responsive to allergen challenge. INTERVENTIONS: During each challenge, subjects
      received a single dose of mometasone + ketotifen or mometasone + placebo. MAIN
      OUTCOME MEASURES AND RESULTS: 47 subjects were randomised, and 44 completed both
      treatment sequences. Efficacy was based on mean area under the curve (AUC) values
      for symptom relief scores over time, with the primary variable being the AUC 4-6
      hours postdose (AUC(4-6)) for relief of ocular itching. Between-treatment
      differences were assessed using analysis of variance. While improvement in ocular
      itching (AUC(4-6)) was observed with both treatments, improvement was
      significantly (p = 0.014) better with mometasone + ketotifen versus mometasone +
      placebo, as was improvement based on AUC(0-6) (p = 0.009) and AUC(0-2) (p =
      0.006). Similar trends (in favour of mometasone + ketotifen) were observed for
      improvements in ocular redness, running nose, sneezing and ocular/nasal composite
      scores (p </= 0.05). None of the safety findings (slit-lamp biomicroscopy, vital
      signs, adverse events) were clinically significant. One subject discontinued
      treatment due to mild pharyngitis. CONCLUSION: Ketotifen eye drops adjunctive to
      mometasone nasal spray provided greater relief of both ocular and nasal signs and
      symptoms than mometasone alone in subjects with SARC.

PMID- 17535074
TI  - Pharmacokinetic-pharmacodynamic modelling of ketamine in six neurotraumatised
      intensive care patients.

PMID- 17535075
TI  - Reversibility of tacrolimus-induced alopecia : a case report and literature
      review.

PMID- 17535076
TI  - Bilateral Skin Ulceration after Injection of Pegylated Interferon-alpha-2b in a
      Patient with Chronic Hepatitis C.

PMID- 17535077
TI  - Effect of add-on acarbose to insulin therapy in routine clinical practice.
AB  - OBJECTIVE AND DESIGN: This post-marketing surveillance study collected data on
      the efficacy and tolerability of acarbose in patients with insulin-treated type 2
      diabetes mellitus and, in particular, on its effect on postprandial blood glucose
      under normal daily practice conditions. PATIENTS AND METHODS: A total of 1142
      patients were included in this observational study in which the treating
      physicians had sole responsibility for determining acarbose doses and other
      therapeutic measures. Efficacy parameters consisted of fasting and postprandial
      blood glucose and glycosylated haemoglobin (HbA(1c)). Additionally, cholesterol,
      triglycerides and weight were analysed. All patient data had to be recorded by
      the attending physician on a case report form. Patients were asked to self
      monitor blood glucose daily after breakfast (1h) and to keep a diary. RESULTS:
      Mean HbA(1c) improved by 0.9%, fasting blood glucose by 32.4 mg/dL, and
      postprandial hyperglycaemia by 49.7 mg/dL during the observation period compared
      with baseline. Comparable results were obtained in combination with conventional,
      functional or intensive insulin therapy. Mean weight was reduced by 0.7kg. The
      incidence of acarbose-related side effects was low (6.9%) and consisted mostly of
      gastrointestinal complaints. The majority of patients assessed acarbose treatment
      positively. CONCLUSION: The addition of acarbose to different insulin regimens
      provided an efficacious and safe treatment for better glycaemic and weight
      control.

PMID- 17535078
TI  - Drug Interaction of Fluvoxamine and Fluoxetine with Nevirapine in HIV-1-Infected
      Individuals.
AB  - OBJECTIVE: To evaluate the possible pharmacokinetic interactions between
      nevirapine and fluvoxamine or fluoxetine in patients with HIV-1 infection.
      PATIENTS AND METHODS: Patients who were using fluvoxamine or fluoxetine
      concomitantly were chosen from an unselected cohort (n = 173) of HIV-1-infected
      individuals using a nevirapine-containing regimen (study group). HIV-1-infected
      patients using nevirapine without fluvoxamine or fluoxetine and non-HIV-infected
      individuals who were using fluvoxamine and fluoxetine were included as controls.
      The influence of fluvoxamine and fluoxetine on the pharmacokinetics of nevirapine
      was investigated with a previously developed population pharmacokinetic model.
      Concomitant use of fluvoxamine or fluoxetine was tested independently as
      covariate for apparent clearance (CL/F) of nevirapine using nonlinear mixed
      effect modelling (NONMEM). Furthermore, to explore the influence of nevirapine on
      the pharmacokinetics of fluvoxamine and fluoxetine, dose-normalised
      concentrations of fluvoxamine and fluoxetine from the study group were compared
      with those of the controls. RESULTS: Of the 173 HIV-1-infected individuals, 14
      were using fluoxetine (n = 7) or fluvoxamine (n = 7) simultaneously with
      nevirapine. In addition, 17 and 29 individuals were identified as controls for
      the fluoxetine- and fluvoxamine-group, respectively. Concomitant use of
      fluvoxamine resulted in a significant reduction of 33.7% in CL/F of nevirapine;
      this reduction in CL/F appeared to be dose-dependent. Concomitant use of
      fluoxetine had no influence on the pharmacokinetics of nevirapine. Conversely,
      nevirapine significantly lowered plasma levels of fluoxetine plus norfluoxetine
      (seproxetine). In contrast, no significant difference was observed in dose
      normalised concentrations of fluvoxamine when the controls were compared with the
      study group. CONCLUSION: We advise that special attention is paid to HIV-1
      infected indivi-duals using a nevirapine-containing regimen and fluvoxamine or
      fluoxetine con-comitantly, since pharmacokinetic interactions have been observed.

PMID- 17535079
TI  - Comparison of the effects of policosanol and atorvastatin on lipid profile and
      platelet aggregation in patients with dyslipidaemia and type 2 diabetes mellitus.
AB  - BACKGROUND: Diabetes mellitus and hypercholesterolaemia increase the risk for
      coronary heart disease, with type 2 diabetes mellitus being the most prevalent
      form of diabetes, frequently accompanied by dyslipidaemia. The main goal of
      dyslipidaemia control in nondiabetic and diabetic patients is to lower elevated
      low-density lipoprotein-cholesterol (LDL-C) levels. Policosanol is a cholesterol
      lowering drug, purified from sugarcane wax, with a therapeutic range of 5-20
      mg/day, which significantly reduces LDL-C levels. Atorvastatin is an HMG-CoA
      reductase inhibitor that, across its dose range (10-80 mg/day), has shown
      significantly greater lipid-lowering effects than all previously marketed
      statins. OBJECTIVE: To compare the effects on lipid profile and platelet
      aggregation of policosanol and atorvastatin in patients with dyslipidaemia due to
      type 2 diabetes. PATIENTS AND METHODS: This randomised, single-blind, parallel
      group study was conducted in patients with type 2 diabetes (fasting glucose </=7
      mmol/L and glycosylated haemoglobin [HbA(1c)] <8.5%) and high LDL-C levels
      (>/=3.0 mmol/L). After 6 weeks on a cholesterol-lowering diet, 40 patients were
      randomised to policosanol or atorvastatin 10mg tablets taken once daily with the
      evening meal for 8 weeks. Assessments of lipid profile, platelet aggregation
      tests, safety indicators and adverse events were performed. RESULTS: After 8
      weeks of therapy, policosanol significantly lowered LDL-C by 25.7% (p < 0.0001
      versus baseline) and total cholesterol (TC) by 18.2% (p < 0.001 versus baseline).
      In turn, atorvastatin 10 mg/day decreased LDL-C by 41.9% and TC by 31.5% (p <
      0.0001 versus baseline). Atorvastatin was more effective than policosanol in
      reducing LDL-C and TC (p < 0.001). Policosanol also significantly reduced the
      TC/high-density lipoprotein-cholesterol (HDL-C) ratio (25.2%; p < 0.0001) and
      triglycerides (15.6%; p < 0.001), while atorvastatin lowered TC/HDL-C by 30.5% (p
      < 0.0001) and triglycerides by 13.9% (p < 0.001); the reductions on these
      variables were similar in the two groups. Policosanol, but not atorvastatin,
      significantly increased HDL-C (11.1%; p < 0.01), the effect being significantly
      different from that of atorvastatin (p < 0.0001). Also, policosanol, but not
      atorvastatin, significantly inhibited platelet aggregation induced by arachidonic
      acid 0.75 and 1.5 mmol/L (39.0% and 33.3%, respectively) and by collagen 0.25 and
      0.5 mug/mL (15.7% and 28.5%, respectively) [p < 0.001]; these inhibitions were
      significantly different (p < 0.05) from the changes that occurred with
      atorvastatin. Neither drug significantly changed platelet aggregation elicited by
      adenosine diphosphate (ADP). Both treatments were well tolerated, with glycaemic
      control being unaffected. Neither drug impaired physical safety indicators or
      glucose control indicators (fasting glucose and HbA(1c)). Atorvastatin
      significantly increased levels of alanine aminotransferase (ALT) [p < 0.05] and
      creatine phosphokinase (CPK) [p < 0.01], while policosanol did not significantly
      change any safety indicator. Only three atorva-statin recipients showed
      individual values of ALT and CPK that were moderately enhanced (<3 times above
      the normal upper limit). No patients withdrew from the study. Four patients
      reported adverse events: two policosanol (insomnia and pruritus) and two
      atorvastatin (myalgia and raised arterial blood pressure) recipients. CONCLUSION:
      Policosanol (10 mg/day) for 8 weeks was less effective than similar doses of
      atorvastatin in reducing LDL-C and TC in patients with dyslipidaemia due to type
      2 diabetes, but more effective in increasing HDL-C. Both drugs similarly reduced
      the TC/HDL-C ratio and triglycerides. Policosanol showed additional advantages
      regarding inhibition of platelet aggregation. Nevertheless, further studies of
      longer duration and using dose-titration schemes to achieve LDL-C goals are
      needed for wider conclusions about the respective effects of these two drugs in
      such a population subset.

PMID- 17535080
TI  - Nimesulide versus Ibuprofen for Postoperative Tonsillectomy Pain : A Double
      Blind, Randomised, Active Comparator-Controlled Clinical Trial.
AB  - BACKGROUND AND OBJECTIVE: Nonsteroidal anti-inflammatory drugs are effective
      analgesics but their use during tonsillectomy is controversial because of the
      risk of postoperative bleeding. The aim of this study was to compare the
      analgesic efficacy and safety of nimesulide, a preferential cyclo-oxygenase type
      2 inhibitor, with ibuprofen in the treatment of pain after tonsillectomy. STUDY
      DESIGN: A prospective, double-blind, randomised clinical trial. PATIENTS AND
      METHODS: A total of 80 consenting generally healthy patients, aged 14-58 years,
      undergoing tonsillectomy were randomly assigned to receive either nimesulide
      100mg or ibuprofen 800mg orally 60 minutes before surgery. Subsequent doses of
      the same study medication were administered at 12-hour intervals for the first 7
      days, and thereafter when needed. During the first 24 postoperative hours in
      hospital oxycodone was used for rescue analgesia, and after discharge patients
      were allowed to use a paracetamol-codeine combination for breakthrough pain.
      Recovery was recorded up to 3 weeks after surgery. RESULTS: The need for rescue
      analgesia during the first 24 hours was similar in the two study groups; 0-7
      doses (mean +/- SD 3.3 +/- 1.7 doses) in the nimesulide group and 0-11 doses (3.3
      +/- 2.4 doses) in the ibuprofen group. After discharge significant differences
      were found between the two study groups in favour of the nimesulide-treated
      patients. Cessation of significant pain while swallowing occurred after 3-19
      (10.9 +/- 3.8) days in the nimesulide group versus 7-20 (12.9 +/- 3.3) days in
      the ibuprofen group (p = 0.041), and return to normal daily activities occurred
      after 3-21 (10.3 +/- 4.9) days in the nimesulide group versus after 3-19 (12.7 +/
      4.2) days in the ibuprofen group (p = 0.048). At 3 weeks, six of 33 patients in
      the nimesulide group versus 15 of 37 patients in the ibuprofen group had pain
      during swallowing (p = 0.049). One patient (3%) in the nimesulide group and five
      patients (12%) [p = 0.22] in the ibuprofen group needed electrocautery to stop
      postoperative bleeding. CONCLUSION: Oral nimesulide was as effective as ibuprofen
      in pain management after tonsillectomy, and nimesulide improved the recovery
      after discharge.

PMID- 17535081
TI  - Bioavailability of a Divalproex Extended-Release Formulation versus the
      Conventional Divalproex Formulation in Adult Patients Receiving Enzyme-Inducing
      Antiepileptic Drugs.
AB  - OBJECTIVES: To compare the bioavailability of divalproex extended release
      (divalproex-ER) given once daily relative to the conventional divalproex
      formulation given once every 8 hours, using various divalproex-ER doses that are
      8-20% greater than the corresponding divalproex total daily doses. DESIGN AND
      SUBJECTS: This multiple-dose, fasting, randomised, two-period, crossover design
      study in 76 subjects with epilepsy taking a concomitant enzyme-inducing
      antiepileptic drug compared the bioavailability of divalproex once-every-8-hours
      regimens with 8-20% higher daily dose divalproex-ER once-daily regimens. RESULTS:
      The 8-20% higher divalproex-ER once-daily-dose regimens were equivalent, with
      respect to exposure (area under the concentration-time curve; 1551 vs 1539 mg .
      h/L), to the corresponding total daily divalproex dose regimens. The divalproex
      ER maximum concentration central value was significantly lower (83.3 vs 92.6
      mg/L), and the minimum concentration mean was not significantly different (45.8
      vs 44.8 mg/L) from the corresponding values for the divalproex regimen. The peak
      to-trough fluctuation in plasma concentrations was significantly lower for once
      daily divalproex-ER (64%) compared with once-every-8-hours divalproex (79%). The
      size of the divalproex dose and the presence of a concomitant enzyme-inducing
      antiepileptic drug did not have a statistically significant effect on divalproex
      ER/divalproex relative bioavailability. No adverse event occurred in more than 5%
      of subjects on either treatment; all were mild or moderate in severity with none
      resulting in discontinuation. Both tested formulations were well tolerated by the
      subjects. CONCLUSION: This study demonstrated that patients with epilepsy taking
      divalproex may switch to 8-20% higher doses of divalproex-ER and have equivalent
      valproic acid exposure, lower fluctuation in valproic acid concentrations, and
      similar tolerability.

PMID- 17535082
TI  - Oxcarbazepine versus Divalproex Sodium for the Continuing Treatment of Mania.
AB  - BACKGROUND AND OBJECTIVE: Oxcarbazepine, an antiepileptic and a derivative of
      carbamazepine, has been shown to have clinical utility as an antimanic agent.
      This study sought to assess the efficacy and tolerability of oxcarbazepine
      compared with divalproex sodium in the treatment of patients with mania. PATIENTS
      AND METHODS: 57 patients from a large clinical practice who had recently begun
      treatment with divalproex sodium were randomly assigned to one of two treatment
      groups. In this open-label, single (rater)-blind study, group 1 remained on
      treatment with divalproex sodium and group 2 was switched to oxcarbazepine. Both
      treatment groups were followed for 10 weeks after the switch. Pharmacotherapeutic
      efficacy was compared using the Clinician Administered Rating Scale for Mania
      (CARS-M). Weight and adverse events were monitored throughout the study. RESULTS:
      83% of patients using oxcarbazepine showed a decrease in mania as assessed using
      the CARS-M, and 70% showed a net decrease in weight over the 10-week course of
      the study. For the divalproex sodium group, 53% showed a decrease in mania, as
      assessed by CARS-M, and 37% lost weight. CONCLUSION: Oxcarbazepine showed
      comparable efficacy to divalproex sodium, yet appeared to do so with an equal or
      more benign side-effect profile, particularly with regard to weight. These
      results suggest that oxcarbazepine, which has been used in Europe for the
      treatment of mood disorders for some time (albeit used off-label for this
      purpose) may show promise for use in the US as an agent for maintenance of non
      acute mania.

PMID- 17535083
TI  - Long-term improvement of metabolic control by acarbose in type 2 diabetes
      patients poorly controlled with maximum sulfonylurea therapy.
AB  - BACKGROUND AND OBJECTIVE: Multiple oral therapies are required long term for the
      majority of patients with type 2 diabetes mellitus to achieve acceptable
      glycaemic levels; alternatively, insulin therapy has to be initiated. This study
      investigated the addition of acarbose to maximum doses of sulfonylurea in very
      poorly controlled type 2 diabetes patients and assessed its effect in delaying
      further glycaemic deterioration. STUDY DESIGN: In this 78-week, double-blind,
      placebo-controlled European study, patients were randomised to receive acarbose,
      titrated to a maximum dose of 100mg three times daily, or matching placebo.
      Concomitant sulfonylurea treatment (glibenclamide/gliclazide) was to remain
      unchanged throughout the study. A sample size of 171 patients per treatment arm
      was calculated. The primary efficacy analysis was intention to treat. METHODS:
      The change in glycosylated haemoglobin (HbA(1c)) levels from baseline to the end
      of the study was regarded as the primary efficacy variable. Patients whose
      HbA(1c) levels increased above 10.5% on two consecutive visits terminated the
      study prematurely because of insulin administration. Secondary efficacy variables
      included the changes in blood glucose and C-peptide, both at fasting and at the
      1h-postprandial level. PATIENTS: A total of 330 patients (acarbose 164, placebo
      166) were valid for the efficacy analysis. Patients were generally overweight
      (body mass index 29.0 kg/m(2)) and showed very poor metabolic control (HbA(1c)
      >9%, fasting blood glucose >200 mg/dL, and 1h-postprandial blood glucose >300
      mg/dL). RESULTS: Acarbose significantly improved HbA(1c) levels compared with
      placebo (least square mean [LS-mean] difference -0.54%, 95% CI -0.86 to -0.22; p
      = 0.001). A number of patients had to discontinue the study prematurely because
      of insulin administration (24.5% in the placebo and 14.2% in the acarbose group).
      There was a significant LS-mean difference of -14.8 mg/dL (p = 0.0195) in fasting
      blood glucose levels and highly significant differences in 1h-postprandial blood
      glucose (LS-mean difference -33.4 mg/dL, p < 0.0001) and in the rise in blood
      glucose from fasting to 1h-postprandial (LS-mean difference -19.6 mg/dL, p =
      0.0001), all in favour of acarbose. Acarbose was shown to have a good safety
      profile and was generally well tolerated. CONCLUSION: Acarbose was shown to have
      the potential to delay further deterioration of glucose control in type 2
      diabetes patients who are very poorly controlled with maximum sulfonylurea doses.

PMID- 17535084
TI  - Oxcarbazepine in pregnancy and lactation.

PMID- 17535085
TI  - Orofaciodigital syndrome type IV (Mohr-Majewski syndrome): report of a family
      with two affected siblings.
AB  - We report on sibling fetuses with orofaciodigital syndrome (OFDS) type IV (Mohr
      Majewski syndrome). The 1st was a 13-week-old fetus with hypertelorism; a median
      cleft defect of the upper lip, soft palate, and uvula; a polypoid lower lip and
      multiple frenula of the tongue adherent to the mandible; a congenital heart
      defect; pre- and postaxial polydactyly of the upper and preaxial polydactyly of
      the lower limbs; and an intersex genitalia. However, the shortening of both arms
      and forearms was particularly striking, with shortening of the ulna and ulnar
      deviation of both hands. The 2nd fetus was of the same parents, was 11 weeks old,
      and presented with a similar spectrum of malformations. The features of both
      fetuses showed a transitional phenotype between the OFDS type II (Mohr syndrome)
      and the short rib-polydactyly syndrome type II (Majewski syndrome), thus
      extending the known spectrum of the OFDS type IV.

PMID- 17535086
TI  - Microscopic chorionic pseudocysts in placental membranes: a histologic lesion of
      in utero hypoxia.
AB  - Grossly apparent and microscopically intermediate trophoblast-lined subchorionic,
      septal, and cell island cysts are relatively common placental findings. To
      analyze the clinicopathologic correlations of histologically similar but grossly
      inapparent microscopic chorionic pseudocysts (lakes) arising in the chorion laeve
      of placental membranes (mccpm), selected placental and clinical parameters of all
      172 consecutive placentas with mccpm (study group, sg) and all consecutive 3743
      placentas without mccpm (comparative group, cg) from years 1994 through 2005 were
      statistically compared; mccpm were observed in 4.3% of all placentas and in 14.9%
      of placentas from preeclamptic mothers from 24- to 42-week pregnancies, their
      gestational weeks' distribution almost mirroring that of the distribution of
      preeclampsia, with a peak in the middle of the 3rd trimester. Microscopic
      chorionic pseudocysts (lakes) arising in the chorion laeve of placental membranes
      were statistically significantly more common in patients with preeclampsia and
      maternal diabetes mellitus. In placentas with mccpm, decidual arteriolopathy,
      homogeneous placental maturation, global hypoxic pattern of placental injury,
      chorangiosis, placental infarction, laminar necrosis of membranes, stem
      obliterative endarteritis, erythroblasts of fetal blood, and decidual
      hemosiderosis were statistically significantly more common, while acute
      chorioamnionitis, villous fibrosis, and villous edema were less common (P < or =
      0.05). There were no statistically significant differences between sg and cg in
      meconium staining, retroplacental hematoma, perivillous fibrin deposition,
      intervillous thrombi, chronic villitis, chorangiomas, placenta accreta, amnion
      nodosum, and marginate/vallate placenta. Highly statistically significant
      associations of mccpm with preeclampsia and a cluster of placental lesions known
      to be linked to placental hypoxia indicate that the mccpm form in response to
      hypoxia, particularly in patients with preeclampsia; mccpm should therefore be
      regarded and reported as a hypoxia-associated placental lesion.

PMID- 17535087
TI  - A case of composite neuroblastoma composed of histologically and biologically
      distinct clones.
AB  - We report a case of a 12-month-old girl with stage 3 neuroblastoma composed of 2
      distinct clones in the adrenal primary tumor. One clone showed neuroblastoma,
      poorly differentiated subtype with a low mitosis-karyorrhexis index (favorable
      histology), and the other was neuroblastoma, poorly differentiated subtype with a
      high mitosis-karyorrhexis index (unfavorable histology), according to the
      International Neuroblastoma Pathology Classification. Fluorescent-labeled in-situ
      hybridization using the formalin-fixed, paraffin-embedded material showed that
      the MYCN oncogene was amplified in the latter clone but not in the former clone.
      Lymph nodes from ipsilateral and contralateral sides contained metastatic
      neuroblastoma of the latter clone. It is well documented that tumors in the
      Ganglioneuroblastoma, nodular (composite, Schwannian stroma-rich/stroma-dominant
      and stroma-poor) category are composite and composed of multiple clones. To our
      knowledge, however, this is the 1st case report of composite tumor with
      biologically favorable and unfavorable clones in the Neuroblastoma (Schwannian
      stroma-poor) category.

PMID- 17535088
TI  - The problems and promise of central pathology review: development of a
      standardized procedure for the Children's Oncology Group.
AB  - The practice of central histopathologic review by expert pathologists has
      accompanied entry of patients onto multi-institutional therapeutic research
      protocols for the past half-century, and it is still a key component in the
      majority of therapeutic protocols conducted by the Children's Oncology Group
      (COG). Policies regarding pathology review have historically varied but have
      recently been standardized by the COG. Pretreatment central pathology review has
      been used to improve the accuracy of pathology data that is critical to the
      conduct of the study and to ensure that ineligible patients are not enrolled on a
      study. Pretreatment central review is unnecessary when there are established
      criteria for diagnosis, when institutions can uniformly apply these criteria, and
      when diagnoses are reliably reported. Pretreatment central review is appropriate
      when there are established diagnostic criteria and expert reviewers can
      consistently apply them but when institutional diagnoses show significant
      variability. It is inappropriate when there are no standard criteria or when
      variability exists among experts. Retrospective reviews (for example, those
      performed after protocol entry and treatment have occurred) historically have
      been used to verify institutional diagnoses and to record other features of
      tumors, prior to analysis of research questions. However, delayed reporting of
      discrepant diagnoses from retrospective reviews introduced obvious concerns
      regarding the appropriateness of treatment and exposed institutional pathologists
      and clinicians to significant professional risks. This article examines the
      historical usage and current status of the central pathology review process and
      the rationale and indications for its performance.

PMID- 17535089
TI  - Mesenchymal hamartoma of the liver associated with features of Beckwith-Wiedemann
      syndrome and high serum alpha-fetoprotein levels.
AB  - A 5-month-old girl with clinical features of Beckwith-Wiedemann syndrome (BWS),
      including a repaired omphalocele, an earlobe crease, enlarged adrenal glands,
      renal size discrepancy, and hyperinsulinemic hyperglycemia, presented with a 1.9
      cm liver nodule. Markedly increased serum alpha-fetoprotein (AFP) levels
      (1,060,000 mg/L), highly suspicious for hepatoblastoma, were detected, and
      resection of the liver mass was performed. Histologic sections showed features
      characteristic of a mesenchymal hamartoma of the liver (MHL). No features of
      embryonal or fetal hepatocellular proliferation or heterologous stromal
      components were noted. By immunohistochemistry, the hepatocytes expressed AFP,
      but no nuclear accumulation of beta-catenin was present. Electron microscopy
      revealed normal, mature hepatocytes. Here we address the diagnostic challenge of
      the uncommon association of MHL and BWS in the setting of markedly elevated serum
      AFP levels. In addition, we analyze the unusual pancreatic lesion (focal
      endocrine adenomatosis) leading to severe hyperinsulinemic hypoglycemia in a
      patient with possible BWS. We emphasize that MHLs may present with markedly
      increased serum AFP levels, mimicking hepatoblastomas, and may also be part of
      the expanding spectrum of findings of BWS.

PMID- 17535090
TI  - Sudden death in toddlers associated with developmental abnormalities of the
      hippocampus: a report of five cases.
AB  - Sudden unexplained death in childhood (SUDC) is the sudden death of a child older
      than 1 year of age that remains unexplained after review of the clinical history,
      circumstances of death, and autopsy with appropriate ancillary testing. We report
      here 5 cases of SUDC in toddlers that we believe define a new entity associated
      with hippocampal anomalies at autopsy. All of the toddlers died unexpectedly
      during the night, apparently during sleep. Within 48 hours before death, 2
      toddlers had fever, 3 had a minor upper respiratory tract infection, and 3
      experienced minor head trauma. There was a history of febrile seizures in 2 (40%)
      and a family history of febrile seizures in 2 (40%). Hippocampal findings
      included external asymmetry and 2 or more microdysgenetic features. The incidence
      of certain microdysgenetic features was substantially increased in the temporal
      lobes of these 5 cases compared with the temporal lobes of 39 (control) toddlers
      with the causes of death established at autopsy (P < 0.01). We propose that these
      5 cases define a potential subset of SUDC whose sudden death is caused by an
      unwitnessed seizure arising during sleep in the anomalous hippocampus and
      producing cardiopulmonary arrest. Precipitating factors may be fever, infection,
      and/or minor head trauma. Suggested risk factors are a history of febrile
      seizures and/or a family history of febrile seizures. Future studies are needed
      to confirm these initial findings and to define the putative links between sudden
      death, hippocampal anomalies, and febrile seizures in toddlers.

PMID- 17535091
TI  - Accessory liver lobe with mesothelial inclusion cysts in an omphalocele: a new
      malformative association.
AB  - Mesothelial inclusion cysts represent benign lesions that have been reported in a
      wide variety of locations. Peritoneal cysts are observed and visceral involvement
      has been described, notably of intraperitoneal organs such as the spleen and the
      testis. We report the cases of 2 neonates who underwent surgical management of an
      omphalocele. The hernial sac contained an accessory liver lobe, displaying in
      both cases multilocular mesothelial inclusion cysts. The hobnail cells lining the
      cysts exhibited calretinin and cytokeratin immunohistochemical reactivity, as
      well as focal D2-40 reactivity. One of the cases occurred in the setting of a
      Beckwith-Wiedemann syndrome (MIM 130650), an overgrowth disorder notably
      associated with omphalocele and hepatic anomalies and tumors. However, no hepatic
      mesothelial cyst has been described in this syndrome. In the 2nd case the
      omphalocele and the hepatic cysts were the sole lesions observed in the neonate.
      To the best of our knowledge, these 2 cases represent the first description of
      such an association.

PMID- 17535092
TI  - Congenital sialolipoma of parotid gland: a report of rare and recently described
      entity with review of literature.

PMID- 17535093
TI  - Anal and ano-urogenital malformations: a histopathological study of "imperforate
      anus" with a reconstruction of the pathogenesis.

PMID- 17535094
TI  - Anaplastic large cell lymphoma: looks can be deceiving.

PMID- 17535096
TI  - Respiratory virus infection in infants and children.
AB  - The recent availability of diagnostic polymerase chain reaction-based assays for
      the detection of viral pathogens has allowed us to identify the infectious agents
      present in a large percentage of culture-negative specimens. The information
      gained by these studies has led to a reassessment of the prevalence of individual
      viruses in lower respiratory tract infections in both normal and
      immunocompromised children. Pathologic examination of less severe cases
      identified by more sensitive methodologies in immunocompetent children is now
      possible and has prompted the realization that many of the classic features of
      particular viral infections in the lung are in fact hallmarks of fulminant
      disease. In this article we review the body of literature discussing these
      anatomic findings, the approaches taken by those investigators, and the types of
      reagents that are commercially available.

PMID- 17535099
TI  - Transparent development of the WHO rapid advice guidelines.
AB  - Emerging health problems require rapid advice. We describe the development and
      pilot testing of a systematic, transparent approach used by the World Health
      Organization (WHO) to develop rapid advice guidelines in response to requests
      from member states confronted with uncertainty about the pharmacological
      management of avian influenza A (H5N1) virus infection. We first searched for
      systematic reviews of randomized trials of treatment and prevention of seasonal
      influenza and for non-trial evidence on H5N1 infection, including case reports
      and animal and in vitro studies. A panel of clinical experts, clinicians with
      experience in treating patients with H5N1, influenza researchers, and
      methodologists was convened for a two-day meeting. Panel members reviewed the
      evidence prior to the meeting and agreed on the process. It took one month to put
      together a team to prepare the evidence profiles (i.e., summaries of the evidence
      on important clinical and policy questions), and it took the team only five weeks
      to prepare and revise the evidence profiles and to prepare draft guidelines prior
      to the panel meeting. A draft manuscript for publication was prepared within 10
      days following the panel meeting. Strengths of the process include its
      transparency and the short amount of time used to prepare these WHO guidelines.
      The process could be improved by shortening the time required to commission
      evidence profiles. Further development is needed to facilitate stakeholder
      involvement, and evaluate and ensure the guideline's usefulness.

PMID- 17535098
TI  - Anaplastic large cell lymphomas: a study of 75 pediatric patients.
AB  - In this article, we describe the morphologic and immunophenotypic features of 75
      cases of pediatric anaplastic large cell lymphoma (ALCL). According to the World
      Health Organization classification, 49 cases were common subtype ALCL, and
      respectively, 3, 6, and 17 cases were small cell, lymphohistiocytic, or mixed
      histologic variants. Anaplastic lymphoma kinase positivity was detected in 90.7%
      of the tumors and, using a panel of 9 T-cell surface markers, 88% could be
      assigned to the T-cell lineage. A molecular analysis for the T-cell receptor
      gamma (TCR- gamma) and the heavy chain of the immunoglobulin H rearrangements was
      performed on 6/9 ALCLs with a null immunophenotype, and a TCR clonal pattern was
      detected in 5/6 cases. In addition, 94.1% were immunoreactive for 1 or more
      cytotoxic proteins (Tia1, granzyme B, or perforin), and 15% expressed CD56.
      Clusterin, CD83, and Pax5, respectively, expressed in 91.3%, 1.7%, and 0% of the
      ALCLs, were useful biomarkers for the differential diagnosis with Hodgkin's
      lymphomas.

PMID- 17535100
TI  - HIV treatment in a conflict setting: outcomes and experiences from Bukavu,
      Democratic Republic of the Congo.

PMID- 17535101
TI  - Prophylactic and therapeutic efficacy of human monoclonal antibodies against H5N1
      influenza.
AB  - BACKGROUND: New prophylactic and therapeutic strategies to combat human
      infections with highly pathogenic avian influenza (HPAI) H5N1 viruses are needed.
      We generated neutralizing anti-H5N1 human monoclonal antibodies (mAbs) and tested
      their efficacy for prophylaxis and therapy in a murine model of infection.
      METHODS AND FINDINGS: Using Epstein-Barr virus we immortalized memory B cells
      from Vietnamese adults who had recovered from infections with HPAI H5N1 viruses.
      Supernatants from B cell lines were screened in a virus neutralization assay. B
      cell lines secreting neutralizing antibodies were cloned and the mAbs purified.
      The cross-reactivity of these antibodies for different strains of H5N1 was tested
      in vitro by neutralization assays, and their prophylactic and therapeutic
      efficacy in vivo was tested in mice. In vitro, mAbs FLA3.14 and FLD20.19
      neutralized both Clade I and Clade II H5N1 viruses, whilst FLA5.10 and FLD21.140
      neutralized Clade I viruses only. In vivo, FLA3.14 and FLA5.10 conferred
      protection from lethality in mice challenged with A/Vietnam/1203/04 (H5N1) in a
      dose-dependent manner. mAb prophylaxis provided a statistically significant
      reduction in pulmonary virus titer, reduced associated inflammation in the lungs,
      and restricted extrapulmonary dissemination of the virus. Therapeutic doses of
      FLA3.14, FLA5.10, FLD20.19, and FLD21.140 provided robust protection from
      lethality at least up to 72 h postinfection with A/Vietnam/1203/04 (H5N1). mAbs
      FLA3.14, FLD21.140 and FLD20.19, but not FLA5.10, were also therapeutically
      active in vivo against the Clade II virus A/Indonesia/5/2005 (H5N1). CONCLUSIONS:
      These studies provide proof of concept that fully human mAbs with neutralizing
      activity can be rapidly generated from the peripheral blood of convalescent
      patients and that these mAbs are effective for the prevention and treatment of
      H5N1 infection in a mouse model. A panel of neutralizing, cross-reactive mAbs
      might be useful for prophylaxis or adjunctive treatment of human cases of H5N1
      influenza.

PMID- 17535102
TI  - Association of human herpesvirus-6B with mesial temporal lobe epilepsy.
AB  - BACKGROUND: Human herpesvirus-6 (HHV-6) is a beta-herpesvirus with 90%
      seroprevalence that infects and establishes latency in the central nervous
      system. Two HHV-6 variants are known: HHV-6A and HHV-6B. Active infection or
      reactivation of HHV-6 in the brain is associated with neurological disorders,
      including epilepsy, encephalitis, and multiple sclerosis. In a preliminary study,
      we found HHV-6B DNA in resected brain tissue from patients with mesial temporal
      lobe epilepsy (MTLE) and have localized viral antigen to glial fibrillary acidic
      protein (GFAP)-positive glia in the same brain sections. We sought, first, to
      determine the extent of HHV-6 infection in brain material resected from MTLE and
      non-MTLE patients; and second, to establish in vitro primary astrocyte cultures
      from freshly resected brain material and determine expression of glutamate
      transporters. METHODS AND FINDINGS: HHV-6B infection in astrocytes and brain
      specimens was investigated in resected brain material from MTLE and non-MTLE
      patients using PCR and immunofluorescence. HHV-6B viral DNA was detected by
      TaqMan PCR in brain resections from 11 of 16 (69%) additional patients with MTLE
      and from zero of seven (0%) additional patients without MTLE. All brain regions
      that tested positive by HHV-6B variant-specific TaqMan PCR were positive for
      viral DNA by nested PCR. Primary astrocytes were isolated and cultured from seven
      epilepsy brain resections and astrocyte purity was defined by GFAP reactivity.
      HHV-6 gp116/54/64 antigen was detected in primary cultured GFAP-positive
      astrocytes from resected tissue that was HHV-6 DNA positive-the first
      demonstration of an ex vivo HHV-6-infected astrocyte culture isolated from HHV-6
      positive brain material. Previous work has shown that MTLE is related to
      glutamate transporter dysfunction. We infected astrocyte cultures in vitro with
      HHV-6 and found a marked decrease in glutamate transporter EAAT-2 expression.
      CONCLUSIONS: Overall, we have now detected HHV-6B in 15 of 24 patients with
      mesial temporal sclerosis/MTLE, in contrast to zero of 14 with other syndromes.
      Our results suggest a potential etiology and pathogenic mechanism for MTLE.

PMID- 17535103
TI  - HIV impairs opsonic phagocytic clearance of pregnancy-associated malaria
      parasites.
AB  - BACKGROUND: Primigravid (PG) women are at risk for pregnancy-associated malaria
      (PAM). Multigravid (MG) women acquire protection against PAM; however, HIV
      infection impairs this protective response. Protection against PAM is associated
      with the production of IgG specific for variant surface antigens (VSA-PAM)
      expressed by chondroitin sulfate A (CSA)-adhering parasitized erythrocytes (PEs).
      We hypothesized that VSA-PAM-specific IgG confers protection by promoting opsonic
      phagocytosis of PAM isolates and that HIV infection impairs this response.
      METHODS AND FINDINGS: We assessed the ability of VSA-PAM-specific IgG to promote
      opsonic phagocytosis of CSA-adhering PEs and the impact of HIV infection on this
      process. Opsonic phagocytosis assays were performed using the CSA-adherent
      parasite line CS2 and human and murine macrophages. CS2 PEs were opsonized with
      plasma or purified IgG subclasses from HIV-negative or HIV-infected PG and MG
      Kenyan women or sympatric men. Levels of IgG subclasses specific for VSA-PAM were
      compared in HIV-negative and HIV-infected women by flow cytometry. Plasma from
      HIV-negative MG women, but not PG women or men, promoted the opsonic phagocytosis
      of CSA-binding PEs (p < 0.001). This function depended on VSA-PAM-specific plasma
      IgG1 and IgG3. HIV-infected MG women had significantly lower plasma opsonizing
      activity (median phagocytic index 46 [interquartile range (IQR) 18-195] versus
      251 [IQR 93-397], p = 0.006) and levels of VSA-PAM-specific IgG1 (mean
      fluorescence intensity [MFI] 13 [IQR 11-20] versus 30 [IQR 23-41], p < 0.001) and
      IgG3 (MFI 17 [IQR 14-23] versus 28 [IQR 23-37], p < 0.001) than their HIV
      negative MG counterparts. CONCLUSIONS: Opsonic phagocytosis may represent a novel
      correlate of protection against PAM. HIV infection may increase the
      susceptibility of multigravid women to PAM by impairing this clearance mechanism.

PMID- 17535106
TI  - Undertaking research in other countries: further considerations.

PMID- 17535105
TI  - Cost-effectiveness of rapid syphilis screening in prenatal HIV testing programs
      in Haiti.
AB  - BACKGROUND: New rapid syphilis tests permit simple and immediate diagnosis and
      treatment at a single clinic visit. We compared the cost-effectiveness, projected
      health outcomes, and annual cost of screening pregnant women using a rapid
      syphilis test as part of scaled-up prenatal testing to prevent mother-to-child
      HIV transmission in Haiti. METHODS AND FINDINGS: A decision analytic model
      simulated health outcomes and costs separately for pregnant women in rural and
      urban areas. We compared syphilis syndromic surveillance (rural standard of
      care), rapid plasma reagin test with results and treatment at 1-wk follow-up
      (urban standard of care), and a new rapid test with immediate results and
      treatment. Test performance data were from a World Health Organization-Special
      Programme for Research and Training in Tropical Diseases field trial conducted at
      the GHESKIO Center Groupe Haitien d'Etude du Sarcome de Kaposi et des Infections
      Opportunistes in Port-au-Prince. Health outcomes were projected using historical
      data on prenatal syphilis treatment efficacy and included disability-adjusted
      life years (DALYs) of newborns, congenital syphilis cases, neonatal deaths, and
      stillbirths. Cost-effectiveness ratios are in US dollars/DALY from a societal
      perspective; annual costs are in US dollars from a payer perspective. Rapid
      testing with immediate treatment has a cost-effectiveness ratio of $6.83/DALY in
      rural settings and $9.95/DALY in urban settings. Results are sensitive to
      regional syphilis prevalence, rapid test sensitivity, and the return rate for
      follow-up visits. Integrating rapid syphilis testing into a scaled-up national
      HIV testing and prenatal care program would prevent 1,125 congenital syphilis
      cases and 1,223 stillbirths or neonatal deaths annually at a cost of $525,000.
      CONCLUSIONS: In Haiti, integrating a new rapid syphilis test into prenatal care
      and HIV testing would prevent congenital syphilis cases and stillbirths, and is
      cost-effective. A similar approach may be beneficial in other resource-poor
      countries that are scaling up prenatal HIV testing.

PMID- 17535104
TI  - Lithium therapy improves neurological function and hippocampal dendritic
      arborization in a spinocerebellar ataxia type 1 mouse model.
AB  - BACKGROUND: Spinocerebellar ataxia type 1 (SCA1) is a dominantly inherited
      neurodegenerative disorder characterized by progressive motor and cognitive
      dysfunction. Caused by an expanded polyglutamine tract in ataxin 1 (ATXN1), SCA1
      pathogenesis involves a multifactorial process that likely begins with misfolding
      of ATXN1, which has functional consequences on its interactions, leading to
      transcriptional dysregulation. Because lithium has been shown to exert
      neuroprotective effects in a variety of conditions, possibly by affecting gene
      expression, we tested the efficacy of lithium treatment in a knock-in mouse model
      of SCA1 (Sca1(154Q/2Q) mice) that replicates many features of the human disease.
      METHODS AND FINDINGS: Sca1(154Q/2Q) mice and their wild-type littermates were fed
      either regular chow or chow that contained 0.2% lithium carbonate. Dietary
      lithium carbonate supplementation resulted in improvement of motor coordination,
      learning, and memory in Sca1(154Q/2Q) mice. Importantly, motor improvement was
      seen when treatment was initiated both presymptomatically and after symptom
      onset. Neuropathologically, lithium treatment attenuated the reduction of
      dendritic branching in mutant hippocampal pyramidal neurons. We also report that
      lithium treatment restored the levels of isoprenylcysteine carboxyl
      methyltransferase (Icmt; alternatively, Pccmt), down-regulation of which is an
      early marker of mutant ATXN1 toxicity. CONCLUSIONS: The effect of lithium on a
      marker altered early in the course of SCA1 pathogenesis, coupled with its
      positive effect on multiple behavioral measures and hippocampal neuropathology in
      an authentic disease model, make it an excellent candidate treatment for human
      SCA1 patients.

PMID- 17535108
TI  - Natural ventilation for prevention of airborne contagion: conclusions
      overgeneralized.

PMID- 17535110
TI  - How is WHO responding to global public health threats?

PMID- 17535111
TI  - PER-TIM interactions with the photoreceptor cryptochrome mediate circadian
      temperature responses in Drosophila.
AB  - Drosophila cryptochrome (CRY) is a key circadian photoreceptor that interacts
      with the period and timeless proteins (PER and TIM) in a light-dependent manner.
      We show here that a heat pulse also mediates this interaction, and heat-induced
      phase shifts are severely reduced in the cryptochrome loss-of-function mutant
      cry(b). The period mutant per(L) manifests a comparable CRY dependence and
      dramatically enhanced temperature sensitivity of biochemical interactions and
      behavioral phase shifting. Remarkably, CRY is also critical for most of the
      abnormal temperature compensation of per(L) flies, because a per(L); cry(b)
      strain manifests nearly normal temperature compensation. Finally, light and
      temperature act together to affect rhythms in wild-type flies. The results
      indicate a role for CRY in circadian temperature as well as light regulation and
      suggest that these two features of the external 24-h cycle normally act together
      to dictate circadian phase.

PMID- 17535112
TI  - Setting the tempo in development: an investigation of the zebrafish somite clock
      mechanism.
AB  - The somites of the vertebrate embryo are clocked out sequentially from the
      presomitic mesoderm (PSM) at the tail end of the embryo. Formation of each somite
      corresponds to one cycle of oscillation of the somite segmentation clock--a
      system of genes whose expression switches on and off periodically in the cells of
      the PSM. We have previously proposed a simple mathematical model explaining how
      the oscillations, in zebrafish at least, may be generated by a delayed negative
      feedback loop in which the products of two Notch target genes, her1 and her7,
      directly inhibit their own transcription, as well as that of the gene for the
      Notch ligand DeltaC; Notch signalling via DeltaC keeps the oscillations of
      neighbouring cells in synchrony. Here we subject the model to quantitative tests.
      We show how to read temporal information from the spatial pattern of stripes of
      gene expression in the anterior PSM and in this way obtain values for the
      biosynthetic delays and molecular lifetimes on which the model critically
      depends. Using transgenic lines of zebrafish expressing her1 or her7 under heat
      shock control, we confirm the regulatory relationships postulated by the model.
      From the timing of somite segmentation disturbances following a pulse of her7
      misexpression, we deduce that although her7 continues to oscillate in the
      anterior half of the PSM, it governs the future somite segmentation behaviour of
      the cells only while they are in the posterior half. In general, the findings
      strongly support the mathematical model of how the somite clock works, but they
      do not exclude the possibility that other oscillator mechanisms may operate
      upstream from the her7/her1 oscillator or in parallel with it.

PMID- 17535114
TI  - From research to policy and practice: the School of the 21st Century.
AB  - Current education reform policies focus on raising academic achievement and
      ensuring that all students have access to high-quality education. Because the
      achievement gap is apparent even before children enter school, the authors
      believe that education reform must encompass the early childhood years. The
      current dialogue about universal preschool presents an opportunity to address the
      need for a national system for early care and education. The authors believe this
      system should provide quality child care and preschool experiences for all
      children and embrace a whole-child approach that nurtures not only cognitive
      development but physical and mental health and social-emotional behaviors that
      are also important to successful schooling. The School of the 21st Century
      provides an example of an effective early care and education system using the
      public schools. The authors' work with the School of the 21st Century shows that
      schools can provide high-quality, developmentally appropriate care and that these
      programs benefit later school performance.

PMID- 17535113
TI  - All beta cells contribute equally to islet growth and maintenance.
AB  - In healthy adult mice, the beta cell population is not maintained by stem cells
      but instead by the replication of differentiated beta cells. It is not known,
      however, whether all beta cells contribute equally to growth and maintenance, as
      it may be that some cells replicate while others do not. Understanding precisely
      which cells are responsible for beta cell replication will inform attempts to
      expand beta cells in vitro, a potential source for cell replacement therapy to
      treat diabetes. Two experiments were performed to address this issue. First, the
      level of fluorescence generated by a pulse of histone 2B-green fluorescent
      protein (H2BGFP) expression was followed over time to determine how this marker
      is diluted with cell division; a uniform loss of label across the entire beta
      cell population was observed. Second, clonal analysis of dividing beta cells was
      completed; all clones were of comparable size. These results support the
      conclusion that the beta cell pool is homogeneous with respect to replicative
      capacity and suggest that all beta cells are candidates for in vitro expansion.
      Given similar observations in the hepatocyte population, we speculate that for
      tissues lacking an adult stem cell, they are replenished equally by replication
      of all differentiated cells.

PMID- 17535116
TI  - Does political ideology moderate stress: the special case of soldiers conducting
      forced evacuation.
AB  - This study examined the moderating role of political ideology on psychological
      outcomes for Israeli soldiers participating in the forced evacuation of Jewish
      settlements from Gaza. Change in psychopathology and well-being was assessed for
      3 concurrent mission groups differing in their political ideological
      contentiousness--forced evacuation, Gaza security, and Northern border security.
      After soldiers in each mission group were classified on the basis of relatively
      left- or right-wing political ideological tendencies, the authors examined
      differential impact of each mission on soldiers of differing political ideology.
      Results confirmed strong moderation effects of political ideology on
      psychological outcomes in these extreme contexts. Implications for research,
      prevention, and treatment are discussed.

PMID- 17535115
TI  - Changes in diagnostic criteria of PTSD: implications from two prospective
      longitudinal studies.
AB  - This study assesses differences in PTSD rates according to different sets of
      diagnostic criteria. Two samples have been studied: one comprised of 286 combat
      stress reaction (CSR) casualties and 218 non-CSR veterans from the Lebanon war
      (Study 1); the other of 95 ex-POWs and 101 non-POWs from the Yom Kipur war (Study
      2). Participants were administered two versions of the PTSD inventory based on
      different Diagnostic and Statistical Manual of Mental Disorders (DSM) editions:
      DSM-III and DSM-IV in Study 1 and DSM-III-R and DSM-IV in Study 2. PTSD rates
      declined when criteria of more recent DSM editions were applied. In addition,
      findings clearly demonstrate the importance of the dysfunction criterion (F) in
      PTSD. The highly complex nature of the PTSD diagnosis is discussed, as well as
      the important role of dysfunction and distress.

PMID- 17535117
TI  - Immigration and attendant psychological sequelae: a comparison of three waves of
      Iraqi immigrants.
AB  - Acculturation, the process by which individuals or groups transition from one or
      more cultures into another, can be complex and often stressful. In many cases,
      reason for immigration can contribute, both positively and negatively, to levels
      of acculturative stress. Immigrants to the United States from Iraq over the past
      several decades have shifted in terms of prevalence, reason for and ease of
      immigration, and pre and postmigration trauma among individuals and groups. The
      authors examined the psychological by-products of acculturative stress by
      measuring posttraumatic stress disorder, anxiety, and depression among three
      distinct waves of immigrants from Iraq. The authors found support for the
      hypotheses that these variables were positively correlated with recency of
      immigration. Implications for psychological practitioners are discussed.

PMID- 17535118
TI  - Witness and nonwitness children's violent and peaceful behavior in different
      types of simulated conflict with peers.
AB  - The violent and peaceful behaviors of 115 children who had or had not witnessed
      domestic violence were measured in five types of simulated conflict. Witnesses
      did not differ from nonwitnesses in conflicts involving limited resources,
      jealousy over possessions, or intimidation; witnesses were significantly more
      violent in conflicts involving aggression and exclusion. The most violent
      responses were found among abusers' sons who had been excluded by peers.

PMID- 17535119
TI  - Differentiating the culturally-based help-seeking patterns of immigrant parents
      from the former Soviet Union by comparison with parents in Russia.
AB  - Whom do immigrant parents turn to when their children encounter problems? To
      begin to answer this question, the help-seeking patterns of 100 immigrant parents
      from the Former Soviet Union were compared with 100 parents in Russia, with the
      goal to differentiate patterns that were more likely to be culturally based from
      those reflective of the new social context of this immigrant population in
      Israel. Similarities were found in the level of willingness and rationale for
      reluctance to seek help from formal sources. Differences were found in the level
      of willingness to seek help from informal resources and in the nature of the
      problems justifying help-seeking. Such knowledge can inform efforts to reduce
      barriers that immigrant parents confront in situations in which their children
      could benefit from help, but they do not seek it.

PMID- 17535120
TI  - Psychosocial correlates of self-reported coping among Japanese Americans interned
      during World War II.
AB  - This study investigated psychosocial correlates of self-reported internment
      coping among Japanese Americans who were incarcerated during World War II.
      Economic, physical, emotional, and total coping were assessed in relation to
      demographics, distal internment characteristics (age interned and length of
      internment), proximal internment variables (internment talk with parents,
      negative internment communications and emotions, in-group preference and
      associations), and individual personality variables (self-esteem and locus of
      control). Although relationships with distal variables were nonsignificant,
      proximal variables of negative communications and emotions and preference for
      Japanese Americans were significantly associated with coping reports. Self
      esteem, locus of control, and income were partial mediators of internment coping
      ratings. Findings are discussed in relation to the complexities of assessing long
      term coping responses to historical trauma.

PMID- 17535122
TI  - Literacy and depressive symptomatology among pregnant Latinas with limited
      English proficiency.
AB  - Latina immigrants with limited English proficiency face significant obstacles to
      using maternal health services. Using a measure of reading skill and problem
      solving in the health context (the Spanish version of the Test of Functional
      Health Literacy in Adults), the authors assessed the association between literacy
      in Spanish and depressive symptomatology among 99 Latinas receiving prenatal care
      who had limited English proficiency. After adjusting for potential confounds,
      women with inadequate literacy were found to be more than twice as likely to have
      Center for Epidemiological Studies-Depression Scale scores greater than 16 (the
      standard clinical threshold) than women with adequate literacy. The association
      between low literacy and depressive symptomatology among pregnant Latinas
      deserves further investigation and should be considered when designing health
      services for this vulnerable and growing population.

PMID- 17535121
TI  - Latino immigrants' intentions to seek depression care.
AB  - This study examined the role that illness perceptions, attitudes toward
      depression treatments, and subjective norms played in Latino immigrants'
      intentions to seek depression care. Ninety-five Latino immigrant patients were
      presented a vignette depicting an individual with major depression and
      interviewed about their intentions to seek care if confronted with a similar
      situation. Patients' preferences were to rely on informal sources of care first,
      and then turn to formal sources to cope with depression. Findings showed Latinos
      immigrants' help-seeking intentions for depression were a function of their views
      of depression, attitudes toward their doctors' interpersonal skills, and social
      norms related to seeking professional care after controlling for demographics,
      health insurance status, acculturation, clinical characteristics, perceived
      barriers to care, and past service use.

PMID- 17535123
TI  - Uses of ministerial support by African Americans: a focus group study.
AB  - This focus group study examines the use of ministerial support among African
      American adults with regard to (1) the issues taken to ministers by church
      members, (2) the issues not taken to ministers by church members, and (3) the
      factors that inform people's decisions about whether or not to seek ministerial
      support. Content analysis of narratives from 13 focus groups revealed significant
      overlap in the range of concerns for which people seek support and those issues
      for which they will not seek ministerial help. The factors that influence
      peoples' decisions included shame as well as evaluations of minister character,
      sincerity, and skill set. Narrative examples are used to elucidate each theme,
      and the implications of the findings for theory, research, and practice are
      discussed.

PMID- 17535124
TI  - Maternal HIV/AIDS and depressive symptoms among inner-city African American
      youth: the role of maternal depressive symptoms, mother-child relationship
      quality, and child coping.
AB  - This study was designed to examine interactions between psychosocial risk (i.e.,
      maternal depressive symptoms) and protective (i.e., child coping skills and
      mother-child relationship quality) correlates of depressive symptoms among inner
      city African American children of mothers with and without HIV/AIDS. Two primary
      hypotheses were tested: (a) whether these correlates interact differently in HIV
      infected and noninfected samples and (b) whether child coping skills and a
      positive mother-child relationship interact to protect children from developing
      depressive symptoms in the context of maternal HIV infection. Results indicated
      that (a) a positive mother-child relationship, but not child coping skills, was
      protective in the HIV-infected sample when maternal depressive symptoms were high
      and (b) the combination of a positive mother-child relationship and child coping
      skills was associated with the lowest level of child depressive symptoms in the
      HIV-infected sample. These findings highlight the differential importance of
      various risk and protective mechanisms for HIV-infected and noninfected African
      American samples and, as such, have preventative implications for children of HIV
      infected women.

PMID- 17535125
TI  - Defining characteristics and potential consequences of caretaking burden among
      children living in urban poverty.
AB  - Parentification of children has not been the focus of much empirical research.
      Consequently, this study was designed to explore the defining characteristics and
      potential consequences of caretaking burden in a sample of 356 children living in
      urban poverty. In a series of multivariate analyses, characteristics of the
      children, vocational-educational status of their mothers, and family structure
      correlated with caretaking burden more consistently than psychiatric, substance
      use, or personality problems in the mothers. Moreover, responsibility to care for
      mother, more so than responsibility for household chores or the care of siblings,
      consistently correlated with the psychosocial adjustment of the children.
      However, even the highest levels of caretaking burden were not consistently
      associated with clinically significant compromise of psychosocial adjustment.

PMID- 17535126
TI  - Family structure variations in patterns and predictors of child victimization.
AB  - In a national probability sample of 1,000 children aged 10-17, youth from single
      parent and stepfamilies experienced higher rates of several different kinds of
      victimization compared with youth living with two biological parents. Youth in
      stepfamilies had the highest overall rates of victimization and the greatest risk
      from family perpetrators, including biological parents, siblings, and
      stepparents. Elevated risk in stepfamilies was fully explained by their higher
      levels of family problems. Victimization risk in single parent families was more
      affected by their lower socioeconomic status and residence in more violence
      neighborhoods and schools.

PMID- 17535127
TI  - Trauma exposure and child abuse potential: investigating the cycle of violence.
AB  - This study was designed to ascertain the relationship between trauma exposure and
      child abuse potential, considering a number of demographic and trauma-specific
      factors. The sample consisted of 1,680 caregivers with open, substantiated cases
      of abuse or neglect who were evaluated at a university-based outpatient
      assessment and treatment center. As part of a larger battery of instruments, the
      participants completed the Child Abuse Potential Inventory (CAPI) and a trauma
      history screen. In partial support of the proposed hypotheses, univariate and
      multivariate analyses revealed important differences in CAPI scores between the
      no-trauma-exposure group and the child-only, adult-only, and child-adult exposure
      groups. In addition, the type of trauma, age, and gender proved to be powerful
      predictors of elevated CAPI scores. These findings advance understanding of the
      developmental and cumulative effects of trauma exposure and suggest a profile of
      individuals who may be at risk for developing characteristics similar to known
      physical abusers.

PMID- 17535128
TI  - Mothers' violence victimization and child behavior problems: examining the link.
AB  - The current study examined the link between parents' experience of violence
      victimization and child outcomes, in 197 mother-child dyads recruited from low
      income urban neighborhoods. At recruitment (when children were between 6 and 18
      months old), demographic factors, child behavioral outcomes, mother-child
      interactions, mothers' psychosocial functioning, and mothers' history of violence
      victimization were assessed. Child behavioral outcomes, mother-child
      interactions, and mothers' psychosocial functioning were assessed again at age 4.
      Mothers' history of victimization as children (but not as adults) uniquely
      predicted child behavior problems at age 4. Three classes of possible mediators
      were examined: demographics, maternal psychosocial functioning, and mother-child
      interactions. Of these, only mother psychological aggression toward child met
      preliminary criteria for mediation; it partially mediated the link between mother
      childhood victimization and child behavioral outcomes. Maternal depressive
      symptoms and young age at child's birth independently predicted child behavior
      problems, but did not act as mediators. Mothers' early experiences with violence
      victimization appear to exert an important influence on child behavioral
      outcomes; this influence appears to be mediated, in part, by mothers'
      psychological aggression toward their children.

PMID- 17535129
TI  - Predictors of depressive symptoms in Chinese American college students: parent
      and peer attachment, college challenges and sense of coherence.
AB  - Based on Antonovsky's salutogenic model, the authors hypothesized that sense of
      coherence would mediate the effects of parent and peer attachment and college
      challenges on depressive symptoms as well as moderate the relationship between
      college challenges and depressive symptoms in Chinese Americans. To test our
      hypotheses, 353 Chinese American college students completed paper-pencil
      measures. Supporting our hypotheses, sense of coherence fully mediated the
      effects of parent and peer attachment on depressive symptom level and served as a
      partial mediator and moderator of the effect of college challenges on depressive
      symptoms. Implications of the study findings for promoting the mental health of
      Chinese American students are discussed.

PMID- 17535130
TI  - Attachment patterns are associated with symptomatology and course of
      schizophrenia in male inpatients.
AB  - The authors tested the hypotheses that the insecure attachment styles of adult
      patients with schizophrenia are associated with (a) diagnosis, (b)
      psychopathological syndromes, and (c) course of the disorder. Thirty
      schizophrenic and 30 age-matching control males answered a self-report
      questionnaire tapping secure, avoidant, and anxious/ambivalent attachment styles.
      The patients were diagnosed using the Structured Clinical Interview for DSM-IV
      (M. B. First, R. L. Spitzer, M. Gibbon, & J. B. W. Williams, 1995), and their
      symptoms were quantified using the Positive and Negative Syndrome Scale (PANSS;
      S. R. Kay, A. Fizhbein, & L. A. Opler, 1987). Patients with schizophrenia did not
      significantly differ from nonpatient controls in secure style mean scores, but
      they exceeded the latter in both avoidant and anxious/ambivalent style scores.
      There were no significant correlations between secure attachment style and any
      PANSS symptom dimensions, whereas avoidant style correlated positively with both
      positive and negative syndromes, and anxious/ambivalent style correlated only
      with positive syndrome. Compared with patients with secure style, those with
      insecure attachment styles were younger at onset of the illness and had longer
      psychiatric hospitalizations. The preliminary results suggest that the insecure
      types of attachment, in particular the avoidant style, are associated with
      schizophrenic symptomatology and course of the illness in male inpatients.
      Further studies using a longitudinal design on extended samples are needed to
      determine the direction of causality in the composite relationships among the
      distinct attachment styles, psychopathology, and course of schizophrenia.

PMID- 17535131
TI  - Subclinical self-harm: range of behaviors, extent, and associated
      characteristics.
AB  - This study examined characteristics associated with mildly injurious (fingernail
      biting, skin picking, etc.) and more injurious (cutting, burning, etc.) self-harm
      (SH) in an undergraduate sample (N = 280); 31% reported mildly injurious SH
      within the past 3 years with no more injurious SH, whereas 20% reported more
      injurious SH within the past 3 years. SH was not associated with significant
      general negative affect or history of physical or sexual abuse, although more
      injurious SH was associated with a history of emotional abuse. A portion of both
      groups reported negative affect regarding their histories of SH. Both types of SH
      were associated with other impulsive and disordered eating behaviors, some
      obsessive-compulsive characteristics, and more somatic symptoms. Similarities and
      differences with clinical SH are discussed, as well as implications for further
      research and treatment. Arguments for and against a continuum view of self-harm,
      as ranging from mild to severe in injuriousness or clinical significance, are
      also discussed.

PMID- 17535132
TI  - Determinants and validity of self-estimates of abilities and self-concept
      measures.
AB  - How accurate are self-estimates of cognitive abilities? An investigation of self
      estimates of verbal, math, and spatial abilities is reported with a battery of
      parallel objective tests of abilities. Self-estimates were obtained prior to and
      after objective ability testing (without test feedback) in order to examine
      whether self-estimates change after direct objective testing experience. Self
      estimates showed small to large effect-size correlations with objective tests-
      larger for math and smaller for verbal. The construct space of self-estimates of
      abilities was explored in the context of self-concept, self-esteem, self
      efficacy, personality, interests, motivational traits, and trait complexes. Self
      efficacy and self-esteem variables showed the highest correlations with self
      estimates of abilities. In general, trait complexes showed the highest
      correlations with verbal ability self-estimates and the lowest correlations with
      math ability self-estimates. Results are discussed in relation to the principle
      of aggregation, the influences of self-evaluative judgments, and uses for self
      estimates of abilities measures.

PMID- 17535133
TI  - The world of competitive Scrabble: Novice and expert differences in visuopatial
      and verbal abilities.
AB  - Competitive Scrabble players spend a mean of 4.5 hr a week memorizing words from
      the official Scrabble dictionary. When asked if they learn word meanings when
      studying word lists, only 6.4% replied "always," with the rest split between
      "sometimes" and "rarely or never." Number of years of play correlated positively
      with expertise ratings, suggesting that expertise develops with practice. To
      determine the effect of hours of practice (M = 1,904), the authors compared
      experts with high-achieving college students on a battery of cognitive tests.
      Despite reporting that they usually memorize word lists without learning
      meanings, experts defined more words correctly. Reaction times on a lexical
      decision task (controlling for age) correlated with expertise ratings, suggesting
      that experts develop faster access to word identification. Experts' superiority
      on visuospatial processing was found for reaction time on 1 of 3 visuospatial
      tests. In a study of memory for altered Scrabble boards, experts outperformed
      novices, with differences between high and low expertise on memory for boards
      with structure-deforming transformations. Expert Scrabble players showed superior
      performance on selected verbal and visuospatial tasks that correspond to
      abilities that are implicated in competitive play.

PMID- 17535134
TI  - Modality-specific imagery reduces cravings for food: an application of the
      elaborated intrusion theory of desire to food craving.
AB  - Based on converging evidence that visual and olfactory images are key components
      of food cravings, the authors tested a central prediction of the elaborated
      intrusion theory of desire, that mutual competition between modality-specific
      tasks and desire-related imagery can suppress such cravings. In each of
      Experiments 1 and 2, 90 undergraduate women underwent an imaginal food craving
      induction protocol and then completed either a visual, auditory, or olfactory
      imagery task. As predicted, the visual and olfactory imagery tasks were superior
      to the auditory imagery task in reducing participants' craving for food in
      general (Experiment 1) and for chocolate in particular (Experiment 2). Experiment
      3 replicated these findings in a sample of 96 women using a nonimagery craving
      induction procedure involving a combination of chocolate deprivation and exposure
      to chocolate cues. Thus, imagery techniques in the visual or olfactory domain
      hold promise for treating problematic cravings in disordered eating populations.

PMID- 17535135
TI  - The role of work habits in the motivation of food safety behaviors.
AB  - The authors considered work habits within an integrated framework of motivated
      behavior. A distinction made between automatic and controlled action led to 2
      measures of work habits: a habit strength measure reflecting the 4
      characteristics of automaticity and a measure of work routines under conscious
      control. Workers at a turkey processing plant (N = 162) responded to an extensive
      survey of these work habits measures with regard to food safety. Results
      indicated that attitudes and subjective norms predicted food safety intentions.
      These intentions, along with perceived behavior control and work habits,
      predicted reports of food safety behaviors. A mediation analysis indicated that
      the work routines measure accounted for the variance in self-reported behavior
      and mediated any effect of the habit strength measure.

PMID- 17535137
TI  - Generalization in the XCSF classifier system: analysis, improvement, and
      extension.
AB  - We analyze generalization in XCSF and introduce three improvements. We begin by
      showing that the types of generalizations evolved by XCSF can be influenced by
      the input range. To explain these results we present a theoretical analysis of
      the convergence of classifier weights in XCSF which highlights a broader issue.
      In XCSF, because of the mathematical properties of the Widrow-Hoff update, the
      convergence of classifier weights in a given subspace can be slow when the spread
      of the eigenvalues of the autocorrelation matrix associated with each classifier
      is large. As a major consequence, the system's accuracy pressure may act before
      classifier weights are adequately updated, so that XCSF may evolve piecewise
      constant approximations, instead of the intended, and more efficient, piecewise
      linear ones. We propose three different ways to update classifier weights in XCSF
      so as to increase the generalization capabilities of XCSF: one based on a
      condition-based normalization of the inputs, one based on linear least squares,
      and one based on the recursive version of linear least squares. Through a series
      of experiments we show that while all three approaches significantly improve
      XCSF, least squares approaches appear to be best performing and most robust.
      Finally we show how XCSF can be extended to include polynomial approximations.

PMID- 17535138
TI  - An information-theoretic analysis on the interactions of variables in
      combinatorial optimization problems.
AB  - In optimization problems, the contribution of a variable to fitness often depends
      on the states of other variables. This phenomenon is referred to as epistasis or
      linkage. In this paper, we show that a new theory of epistasis can be established
      on the basis of Shannon's information theory. From this, we derive a new
      epistasis measure called entropic epistasis and some theoretical results. We also
      provide experimental results verifying the measure and showing how it can be used
      for designing efficient evolutionary algorithms.

PMID- 17535139
TI  - Reducing the number of fitness evaluations in graph genetic programming using a
      canonical graph indexed database.
AB  - In this paper we describe the genetic programming system GGP operating on graphs
      and introduce the notion of graph isomorphisms to explain how they influence the
      dynamics of GP. It is shown empirically how fitness databases can improve the
      performance of GP and how mapping graphs to a canonical form can increase these
      improvements by saving considerable evaluation time.

PMID- 17535140
TI  - Revisiting negative selection algorithms.
AB  - This paper reviews the progress of negative selection algorithms, an
      anomaly/change detection approach in Artificial Immune Systems (AIS). Following
      its initial model, we try to identify the fundamental characteristics of this
      family of algorithms and summarize their diversities. There exist various
      elements in this method, including data representation, coverage estimate,
      affinity measure, and matching rules, which are discussed for different
      variations. The various negative selection algorithms are categorized by
      different criteria as well. The relationship and possible combinations with other
      AIS or other machine learning methods are discussed. Prospective development and
      applicability of negative selection algorithms and their influence on related
      areas are then speculated based on the discussion.

PMID- 17535141
TI  - The end of physiotherapy.

PMID- 17535142
TI  - A Saturday physiotherapy service may decrease length of stay in patients
      undergoing rehabilitation in hospital: a randomised controlled trial.
AB  - QUESTION: Is additional Saturday physiotherapy intervention beneficial for
      inpatients undergoing rehabilitation? DESIGN: Randomised controlled trial with
      concealed allocation, assessor blinding, and intention-to-treat analysis.
      PARTICIPANTS: Two hundred and sixty-two inpatients undergoing rehabilitation in
      an Australian metropolitan hospital. INTERVENTION: The experimental group
      received physiotherapy intervention from Monday to Saturday and the control group
      from Monday to Friday. OUTCOME MEASURES: Primary outcomes were hospital and
      physiotherapy length of stay. Secondary measures were collected to reflect
      patient outcomes (health state, independence, activity, flexibility and strength)
      and burden of care (discharge destination, adverse events, and follow-up
      physiotherapy intervention). RESULTS: There was a 3.2 day reduction for the
      experimental group (95% CI -0.5 to 6.9) in hospital length of stay and a 2.5 day
      reduction (95% CI -0.9 to 5.9) in physiotherapy length of stay. There was no
      significant between-group difference in change from admission to discharge for
      most of the secondary patient outcomes (health state, independence, activity,
      flexibility). The risk of the experimental group being categorised as strong
      relative to the control group was 1.2 (95% CI 0.99 to 1.50). The risk of not
      being discharged home, of having an adverse event, or requiring follow-up
      physiotherapy intervention was no greater for the experimental group than the
      control group. CONCLUSION: The provision of additional Saturday physiotherapy
      intervention resulted in a trend to shorter hospital and physiotherapy length of
      stay without affecting patient outcome unfavourably or increasing burden of care,
      suggesting that a larger multicentre trial is warranted.

PMID- 17535143
TI  - Treadmill walking with body weight support is no more effective than cycling when
      added to an exercise program for lumbar spinal stenosis: a randomised controlled
      trial.
AB  - QUESTION: Is 6 weeks of treadmill walking with body weight support more effective
      than cycling in people with lumbar spinal stenosis when added to an exercise
      program? DESIGN: Randomised controlled trial with concealed allocation, assessor
      blinding, and intention-to-treat analysis. PARTICIPANTS: Sixty-eight patients
      aged 58 (SD 8) with symptoms of lumbar spinal stenosis for 12 weeks (SD 49).
      INTERVENTION: Participants performed either treadmill with body weight support or
      cycling, twice weekly, for 6 weeks. Both groups also received an exercise program
      consisting of heat, lumbar traction, and flexion exercises. OUTCOME MEASURES: The
      primary outcome was disability measured using the modified Oswestry Disability
      Index. Secondary outcomes were disability, measured using the Roland-Morris
      Disability Questionnaire, pain severity, and patient perceived benefit. Measures
      were collected midway through intervention at 3 weeks and after intervention at 6
      weeks. RESULTS: There was no difference between the groups in reduction in
      disability or pain over the 6-week intervention period. The between-group
      difference in the modified Oswestry Disability Index was 3.2 points (95% CI -3.1
      to 7.7) at 6 weeks, and in pain severity was 2 mm on a 100 visual analogue scale
      (95% CI -5 to 10). Furthermore, the wide confidence intervals associated with
      estimates of patient benefit are consistent with no difference between the two
      groups. However, both groups did improve. CONCLUSION: Treadmill with body weight
      support and cycling may be equally effective in the conservative management of
      people with lumbar spinal stenosis. However, the improvement observed in both
      groups was probably a combination of the intervention and the natural course of
      recovery of lumbar spinal stenosis.

PMID- 17535144
TI  - Warm-up reduces delayed onset muscle soreness but cool-down does not: a
      randomised controlled trial.
AB  - QUESTION: Does warm-up or cool-down (also called warm-down) reduce delayed-onset
      muscle soreness? DESIGN: Randomised controlled trial of factorial design with
      concealed allocation and intention-to-treat analysis. PARTICIPANTS: Fifty-two
      healthy adults (23 men and 29 women aged 17 to 40 years). INTERVENTION: Four
      equally-sized groups received either warm-up and cool-down, warm-up only, cool
      down only, or neither warm-up nor cool-down. All participants performed exercise
      to induce delayed-onset muscle soreness, which involved walking backwards
      downhill on an inclined treadmill for 30 minutes. The warm-up and cool-down
      exercise involved walking forwards uphill on an inclined treadmill for 10
      minutes. OUTCOME MEASURE: Muscle soreness, measured on a 100-mm visual analogue
      scale. RESULTS: Warm-up reduced perceived muscle soreness 48 hours after exercise
      on the visual analogue scale (mean effect of 13 mm, 95% CI 2 to 24 mm). However
      cool-down had no apparent effect (mean effect of 0 mm, 95% CI -11 to 11 mm).
      CONCLUSION: Warm-up performed immediately prior to unaccustomed eccentric
      exercise produces small reductions in delayed-onset muscle soreness but cool-down
      performed after exercise does not.

PMID- 17535145
TI  - Sitting training early after stroke improves sitting ability and quality and
      carries over to standing up but not to walking: a randomised trial.
AB  - QUESTION: What is the effect of a sitting training protocol in people early after
      stroke on sitting ability and quality, and does it carry over to mobility?
      DESIGN: Randomised placebo-controlled trial with concealed allocation, assessor
      blinding and intention-to-treat analysis. PARTICIPANTS: Twelve individuals who
      had a stroke less than three months previously and were able to sit unsupported.
      INTERVENTION: The experimental group completed a 2-week sitting training protocol
      that involved practising reaching tasks beyond arm's length. The control group
      completed a 2-week sham sitting training protocol that involved practising
      cognitive-manipulative tasks within arm's length. OUTCOME MEASURES: The primary
      outcome was sitting ability (maximum reach distance). Secondary outcomes were
      sitting quality (reach movement time and peak vertical force through affected
      foot during reaching) and carry over to mobility (peak vertical force through
      affected foot during standing up and walking speed during 10 m Walk Test).
      Outcome measures were taken before and after training and six months later.
      RESULTS: After 2 weeks' training, the experimental group had increased their
      maximum reach distance by 0.17 m (95% CI 0.12 to 0.21), decreased their movement
      time by 0.5 s (95% CI -0.8 to -0.2), increased their peak vertical force through
      the affected foot during reaching by 13% of body weight (95% CI 6 to 20) and
      increased their peak vertical force through the affected foot during standing up
      by 21% of body weight (95% CI 14 to 28) compared with the control group. After 6
      months, significant between-group differences were maintained for maximum reach
      distance and peak vertical force through the affected foot during standing up.
      CONCLUSIONS: The sitting training protocol was both feasible and effective in
      improving sitting and standing up early after stroke and somewhat effective six
      months later.

PMID- 17535146
TI  - Additional exercise does not change hospital or patient outcomes in older medical
      patients: a controlled clinical trial.
AB  - QUESTION: What are the effects of additional exercise on hospital and patient
      outcomes for acutely-hospitalised older medical patients? DESIGN: Controlled
      clinical trial. PARTICIPANTS: 236 Patients aged 65 or older admitted to an acute
      care hospital with a medical illness between October 2002 and July 2003.
      INTERVENTION: The experimental group received usual care plus an individually
      tailored exercise program administered twice daily from hospital admission to
      discharge. The control group received usual care only. OUTCOME MEASURES: The
      primary outcome was discharge destination. Secondary outcomes were measures of
      activity limitation (Barthel Index, Timed Up and Go, Functional Ambulation
      Classification), length of stay, and adverse events. RESULTS: There was no
      significant effect of the additional exercise program on any outcome. There were
      no significant differences between groups for the proportion of the patients
      discharged to home (RR 0.99, 95% CI 0.86 to 1.14) or inpatient rehabilitation (RR
      0.76, 95% CI 0.30 to 1.51) or for measures of activity limitation at hospital
      discharge. A one day difference in length of stay was identified between groups
      but this difference was not significant (p = 0.45). There were no significant
      differences between groups for adverse events: 28-day readmission (RR 1.10, 95%
      CI 0.65 to 1.86), patient mortality (RR 1.15, 95% CI 0.16 to 8.0), intensive care
      admission (RR 0.16, 95% CI 0.01 to 3.13) and falls (RR 0.69, 95% CI 0.17 to
      2.81). CONCLUSION: Additional physiotherapy intervention during hospitalisation
      did not significantly improve hospital or patient outcomes.

PMID- 17535147
TI  - Most people with rheumatoid arthritis undertake leisure-time physical activity in
      the Netherlands: an observational study.
AB  - QUESTION: What type of physical activity or exercise is undertaken by people with
      rheumatoid arthritis? What type of physical activity or exercise do they prefer?
      What is their attitude towards physical activity or exercise? What are the
      perceived barriers to undertaking physical activity or exercise? DESIGN: Survey
      of a random sample of people with rheumatoid arthritis. PARTICIPANTS: Four
      hundred people with rheumatoid arthritis in the Netherlands. RESULTS: Of the 252
      people who returned the questionnaire (63% response) 201 (80%) people
      participated in some type of physical activity or exercise. Significantly more
      inactive people were male, less educated, and older than the active people. Of
      the active people, 45 (22%) participated exclusively in supervised activities, 72
      (36%) in unsupervised activities, and 84 people (42%) combined supervised and
      unsupervised activities. Cycling and walking were the two unsupervised activities
      people performed most often. Supervised group exercise and unsupervised
      individual physical activity were reported as the favourite activities. Further,
      more people preferred being physically active under expert supervision than
      without supervision and preferred water-based over land-based activities. The
      most frequently-mentioned barriers were lack of energy, presence of pain, lack of
      motivation, lack of information, and fear of joint damage. CONCLUSION: The
      majority of people with rheumatoid arthritis participated in some physical
      activity or exercise, mostly under supervision. Preferences for types of activity
      varied, underpinning the need for a variety of options for people with rheumatoid
      arthritis.

PMID- 17535148
TI  - The physiotherapy workforce is ageing, becoming more masculinised, and is working
      longer hours: a demographic study.
AB  - QUESTION: Is the physiotherapy workforce significantly older in 2001 than 1986?
      What is the cumulative attrition of the workforce to 2001 and what is the
      predicted attrition by 2026? Is the workforce becoming masculinised? Is the
      workforce working longer hours? DESIGN: Observational study using Australian
      Bureau of Statistics census data from 1986 to 2001 to predict workforce
      characteristics in 2026. PARTICIPANTS: All physiotherapists who responded to the
      1986, 1991, 1996 and 2001 censuses: 5928, 7106, 8788 and 10039 respondents in
      each year respectively. RESULTS: The physiotherapy workforce has aged
      significantly since 1986 (p < 0.001), and women are older than men (p < 0.001).
      Forty-one percent of the 2001 physiotherapy workforce is predicted to retire by
      2026, although around one-third of physiotherapists continue working after age
      65. While physiotherapy remains a female-dominated profession, the proportion of
      males is increasing and has risen from 16% in 1986 to 27% in 2001.
      Physiotherapists are working longer hours than they did in the past, and while
      this is partly due to the increasing proportion of males in the workforce,
      generation X and Y females are also more likely to work longer hours than their
      predecessors. CONCLUSION: The retirement of older, mostly female,
      physiotherapists may exacerbate existing workforce shortages, particularly in the
      public and aged care sectors. However, the growing proportion of male
      physiotherapists and their generally higher workforce participation may go some
      way to improving labour force capacity overall.

PMID- 17535149
TI  - Intrapulmonary percussive ventilation improves the outcomes of helmet
      ventilation.

PMID- 17535151
TI  - Eccentric exercise and shock-wave therapy benefit patients with chronic Achilles
      tendinopathy.

PMID- 17535150
TI  - Patients with rheumatoid arthritis feel better after exercises in warm water than
      after similar exercises on land.

PMID- 17535152
TI  - Constraint-induced movement therapy improves upper extremity motor function after
      stroke.

PMID- 17535153
TI  - Disabilities of the arms, shoulder and hand questionnaire.

PMID- 17535154
TI  - Goniometry via the internet.

PMID- 17535155
TI  - Caution urged on the concept of lumbar instability.

PMID- 17535156
TI  - Identification, cloning, expression and functional characterization of an astacin
      like metalloprotease toxin from Loxosceles intermedia (brown spider) venom.
AB  - Injuries caused by brown spiders (Loxosceles genus) are associated with
      dermonecrotic lesions with gravitational spreading and systemic manifestations.
      The venom has a complex composition containing many different toxins, of which
      metalloproteases have been described in many different species of this genus.
      These toxins may degrade extracellular matrix constituents acting as a spreading
      factor. By using a cDNA library from an Loxosceles intermedia venom gland, we
      cloned and expressed a 900 bp cDNA, which encoded a signal peptide and a
      propeptide, which corresponded to a 30 kDa metalloprotease, now named LALP
      (Loxosceles astacin-like protease). Recombinant LALP was refolded and used to
      produce a polyclonal antiserum, which showed cross-reactivity with a 29 kDa
      native venom protein. CD analysis provided evidence that the recombinant LALP
      toxin was folded correctly, was still in a native conformation and had not
      aggregated. LALP addition to endothelial cell cultures resulted in de-adhesion of
      the cells, and also in the degradation of fibronectin and fibrinogen (this could
      be inhibited by the presence of the bivalent chelator 1,10-phenanthroline) and of
      gelatin in vitro. Sequence comparison (nucleotide and deduced amino acid),
      phylogenetic analysis and analysis of the functional recombinant toxin revealed
      that LALP is related in both structure and function to the astacin family of
      metalloproteases. This suggests that an astacin-like toxin is present in a animal
      venom secretion and indicates that recombinant LALP will be a useful tool for
      future structural and functional studies on venom and the astacin family.

PMID- 17535157
TI  - Additive effect of multiple pharmacological chaperones on maturation of CFTR
      processing mutants.
AB  - The most common cause of CF (cystic fibrosis) is the deletion of Phe(508)
      (DeltaF508) in the CFTR [CF TM (transmembrane) conductance regulator] chloride
      channel. One major problem with DeltaF508 CFTR is that the protein is defective
      in folding so that little mature protein is delivered to the cell surface.
      Expression of DeltaF508 CFTR in the presence of small molecules known as
      correctors or pharmacological chaperones can increase the level of mature
      protein. Unfortunately, the efficiency of corrector-induced maturation of
      DeltaF508 CFTR is probably too low to have therapeutic value and approaches are
      needed to increase maturation efficiency. We postulated that expression of
      DeltaF508 CFTR in the presence of multiple correctors that bound to different
      sites may have an additive effect on maturation. In support of this mechanism, we
      found that expression of P-glycoprotein (CFTR's sister protein) processing
      mutants in the presence of two compounds that bind to different sites (rhodamine
      B and Hoechst 33342) had an additive effect on maturation. Therefore we tested
      whether expression of DeltaF508 CFTR in the presence of combinations of three
      different classes of corrector molecules would increase its maturation
      efficiency. It was found that the combination of the quinazoline VRT-325 together
      with the thiazole corr-2b or bisaminomethylbithiazole corr-4a doubled the steady
      state maturation efficiency of DeltaF508 CFTR (approx. 40% of total CFTR was
      mature protein) compared with expression in the presence of a single compound.
      The additive effect of the correctors on DeltaF508 CFTR maturation suggests that
      they directly interact at different sites of the protein.

PMID- 17535158
TI  - 'We are all consumers of mental health services': the hidden danger of promoting
      'sameness'.

PMID- 17535159
TI  - Touching their lives: North Western Mental Health's approach to practice
      development in aged mental health.
AB  - The ongoing development of mental health practice is an important issue for
      consumers, carers, and clinicians. This paper outlines a practice development
      project undertaken by North Western Mental Health. The aim of the project was to
      assist nurses and direct care staff working in a residential facility to provide
      individualized, sensitive, therapeutic, and responsive care for long-term clients
      with severe mental illness. A clinical nurse educator was engaged to help
      facilitate changes to both attitudes and practices in a specialist environment
      catering to those with psychiatric, cognitive, and physical health concerns. The
      project identified institutionalized routines and practices that were entrenched
      within the setting and, with support and guidance from a clinical nurse educator,
      encouraged enhancement of clients' experience and choice. Nurses' clinical
      reasoning skills were also extended through this process. The project encouraged
      all staff to develop and maintain an awareness of residents' experience of
      receiving care in a potentially disempowering environment. In particular, nurses
      were challenged to consider how nursing, realized to its full potential, can
      touch the lives of residents and families.

PMID- 17535160
TI  - Technology in nursing scholarship: use of citation reference managers.
AB  - Nurses, especially those in academia, feel the pressure to publish but have a
      limited time to write. One of the more time-consuming and frustrating tasks of
      research, and subsequent publications, is the collection and organization of
      accurate citations of sources of information. The purpose of this article is to
      discuss three types of citation reference managers (personal bibliographic
      software) and how their use can provide consistency and accuracy in recording all
      the information needed for the research and writing process. The advantages and
      disadvantages of three software programs, EndNote, Reference Manager, and
      ProCite, are discussed. These three software products have a variety of options
      that can be used in personal data management to assist researchers in becoming
      published authors.

PMID- 17535161
TI  - Analysis of positive Edinburgh depression scale referrals to a consultation
      liaison psychiatry service in a two-year period.
AB  - Antenatal depression is a depressive episode that begins in pregnancy and is
      often a predictor of postnatal depression. The main aim of this study was to
      examine the prevalence of antenatal depression and other psychiatric conditions
      in women referred to a consultation liaison psychiatry service because of
      positive scores on the Edinburgh Postnatal Depression Scale. The other aim was to
      review known risk factors in the women and note any significant findings. An
      audit of all women referred to the psychiatry team because of positive Edinburgh
      scores during a 2-year period was completed. Information about Edinburgh scores,
      clinical diagnoses at the time of the psychiatric appointment, and factors such
      as relationship status, domestic violence, ethnicity, and substance use was
      noted. According to the Diagnostic and Statistical Manual of Mental Disorders:
      Fourth Edition criteria: 36.5% of the women had an adjustment disorder, 13% had a
      major depression, 10% had dysthymia, 8% had a recurrent depressive disorder, 2%
      had post-traumatic stress disorder, and 2% had a borderline personality disorder.
      The findings demonstrated the usefulness of using a screening tool such as the
      Edinburgh Postnatal Depression Scale in detecting women requiring psychiatric
      intervention and highlighted the importance of a psychiatric interview assessment
      to interpret the scores of screened patients in terms of clinically relevant
      syndromes.

PMID- 17535162
TI  - Nursing processes used in the treatment of patients with bipolar disorder.
AB  - Psychiatric nurses are increasingly being involved in the provision of care for
      outpatients with bipolar disorder. The establishment of a body of knowledge for
      the nursing of these patients is vital for the development of integrated evidence
      based treatment. The literature for the period January 1980 to January 2006 is
      reviewed. A sensitive literature search included not only the nursing care based
      on research results but also nursing care based on experiences acquired by
      practising nurses. The results show that formal research on the nursing of
      patients with a bipolar disorder is remarkably limited. Three quantitative
      studies were identified in five articles and six qualitative studies addressing a
      broad range of topics. The remainder of articles meeting the inclusion criteria
      contained mostly descriptive reports. An overview is presented of the nursing
      processes used during the euthymic stage of a bipolar disorder and during an
      acute episode of (hypo)mania. No specific nursing processes for acute episodes of
      bipolar depression are described in the literature. The results show hardly any
      evidence for the described nursing processes.

PMID- 17535163
TI  - Mental illness and Egyptian families.
AB  - People from Egypt have cultural belief systems about mental illness and its
      causes that are at variance from Anglo-Saxon-derived understandings that
      predominate in Australian psychiatry. These differences in understanding can
      affect how mental health services are experienced and accepted by this cultural
      group. This paper is a review of the literature on Egyptians' beliefs about
      mental illness and how families in Egypt cope with a relative with mental
      illness. Because of limited literature on Egyptians' experience with mental
      illness in Australia, this paper will be used to shed some light on the way in
      which people experience mental illness and communicate this suffering in the
      Australian context, based on what has been known to occur in Egypt. The Zar cult
      and related practices focusing on belief in the evil eye, magic, and evil
      possession will be explored. Historical and contemporary mental health care
      systems in Egypt, and the influence of education and religion are discussed. In
      order to provide culturally sensitive care, nurses need to be aware of possible
      influences on belief systems about mental illness. This paper has the potential
      of helping nurses to gain a deeper understanding of cultures that differ from
      theirs and to provide care to clients and their families based on respect for the
      others' beliefs, values, and practices.

PMID- 17535164
TI  - Role of psychological factors in studying recovery from a transactional stress
      coping approach: implications for mental health nursing practices.
AB  - Over the last decade, the experience of recovering from psychiatric disabilities
      has received increased attention in mental health nursing. Recovery is a complex
      experience that can be understood in terms of construct, process, and outcomes.
      New theoretical frameworks are needed to better understand antecedents, process
      variables, and outcomes related to recovery. Considering that recovery is a
      stressful and challenging experience, the transactional stress-coping theory
      appears relevant to explore the appraisal and coping processes involved in
      recovery. Based on this theory, a new framework has been built to better
      understand the phenomenon of stress in recovery. More specifically, a review of
      the recovery literature had led to the identification of several key recovery
      concepts, which were then linked to major stress-coping concepts, namely
      contextual factors, potential stressors, primary and secondary appraisals, coping
      strategies, and short-term and long-term outcomes. This paper focuses on specific
      types of personal characteristics that are included in the broad category of
      contextual factors, namely psychological factors. These factors may act as coping
      resources, helping people to deal successfully with events interfering with the
      achievement of recovery goals. The main purpose of this paper is to offer a
      detailed discussion about how mental health nursing practices may promote the
      role of psychological factors within the stress-coping process. Three categories
      of psychological factors are discussed: views about oneself, psychological
      empowerment, and personal/philosophical orientations in life. A brief summary of
      the new framework is first offered to introduce its major concepts and basic
      mechanisms.

PMID- 17535165
TI  - Shine: still a glittering moment, or now a little bit tarnished?
AB  - The representation of mental illness in the cinema has a long and varied history.
      Each film emerges from a cultural context and understanding of psychopathology
      and some landmark films have made a profound impact on the way in which
      psychiatric disorders are regarded by the general public. One prime example is
      Shine, produced in 1996 and based on the life of David Helfgott, a child musical
      prodigy who later developed a severe mental illness. However, although the film
      garnered numerous awards and public acclaim, its premises have been questioned
      and the explanatory model of mental illness that it promotes has been criticized.
      This paper examines the cultural forces that shape cinematic representations and
      the example of Shine in particular.

PMID- 17535166
TI  - Depression: the 'invisible grey fog' influencing the midlife health of African
      Canadian women.
AB  - Depression is a topic that is often avoided in discussions among Black women for
      a myriad of reasons. The purpose of this study was to investigate the midlife
      health of Black women living in the province of Nova Scotia, Canada. This paper
      will present one of the key findings of this research; midlife depression. It
      will examine the factors associated with depression among mid-life African
      Canadian women and how these women deal with depression. A triangulation of
      qualitative and quantitative methods guided by the principles of participatory
      action research (PAR) was used in the study. Data collection methods included 50
      in-depth interviews of mid-life African Canadian women aged 40-65, focus groups,
      and workshops as well as the CES-D structured instrument. Purposive sampling
      method was the primary recruitment strategy and 113 people participated in the
      study. Although the women rarely openly discussed depression, they described
      depression as emotional feelings that range from "feeling blue" to being
      clinically depressed. Women viewed midlife depression as the consequence of a
      complex set of circumstances and stressors that they face. At midlife, Black
      women frequently recognize the importance of greater self-care and the need to
      pay more attention to their health, but they are reluctant to do so because they
      have to be "strong" in order to deal with their daily experiences of racism.
      Racism, among other things, leads to accumulated stress and undermines Black
      women's ability to cope and make healthy life choices. This signifies the
      implications of these research findings for clinical practice.

PMID- 17535167
TI  - Consumer advocate and clinician perceptions of consumer participation in two
      rural mental health services.
AB  - Consumer participation has been heralded as the integration of consumer
      perspectives into standard mental health care. Using a qualitative descriptive
      method, this study had two broad aims. First, the study aimed to explore the
      perceptions of consumer advocates and clinicians regarding consumer participation
      in two new regional mental health services. Second, the study aimed to explore
      how broad policy initiatives, related to consumer participation, are enacted at a
      service delivery level. In-depth interviews were conducted with 10 participants,
      recruited from the steering committees of both services. Although all
      participants uniformly commended consumer participation as a reality in mental
      health services, its breadth and depth of influence was not enacted. A systemic
      change to the way consumer participation is funded and incorporated into mental
      health services is required. The incorporation of consumers as stakeholders
      within mental health services requires commitment to the idea, the establishment
      of clear purposes and roles, and commensurate funding to enable consumers to be
      stakeholders with similar resources to other stakeholder groups.

PMID- 17535168
TI  - Oral corticosteroid therapy for acute asthma in children: evidence of efficacy
      and current Australian practice.

PMID- 17535169
TI  - Switched-on Sonic hedgehog: a gene whose activity extends beyond fetal
      development--to oncogenesis.
AB  - Embryonic and fetal development is a highly complex process choreographed by
      several families of genes that regulate early development of the embryo.
      Disruption in the structure and/or function of developmental genes produces
      morphogenic errors of development. One such family is the Hedgehog (Hh)
      signalling pathway, which plays an important role in the embryonal development of
      both invertebrates and vertebrates, including normal development of the brain,
      eye, limbs, foregut and its derivatives. Disruption of the Sonic hedgehog
      expression during critical periods of development is associated with
      developmental disorders of the brain, namely, holoprosencephaly, and the VATER
      association. Inappropriate activation of the pathway in post-embryonic
      development has been demonstrated in several human malignancies, including those
      of the brain and skin, both in children and adults. Specific inhibition of Hh
      signalling in these tumours inhibits growth of a wide range of malignancies. This
      demonstrates a requirement for Hh signalling in these tumours. These observations
      suggest that a better understanding of the genetic control of morphogenesis can
      ultimately provide us with greater knowledge of how congenital structural
      abnormalities occur, as well as the processes that lead to several childhood and
      other tumours. There may be a closer relationship between embryogenesis and
      oncogenesis than previously realised.

PMID- 17535170
TI  - Review of intermittent preventive treatment for malaria in infants and children.
AB  - Malaria is one of the greatest killers of children in the world. Treatment is
      available, but there are problems with affordability, availability, accessibility
      and increasing drug resistance. A new regime, intermittent preventive treatment
      in infants (IPTi) shows promise. It involves giving a treatment course of
      antimalarial drugs, regardless of parasitaemia, at intervals over the first year
      of life. The aim is to decrease the frequency of malarial illness while allowing
      the development of natural immunity. Its strength is that it can be linked with
      the childhood immunisation schedule. Early studies are encouraging, but much
      remains to be learned before its potential place in the prevention of malaria in
      children can be determined and it can safely be introduced as public policy. A
      review of the literature was performed in July 2006 for references relating to
      IPTi and other forms of personal prevention of malaria in infants and children.

PMID- 17535171
TI  - Randomised clinical trial of a group parent education programme for Australian
      indigenous families.
AB  - AIM: Parenting programmes have been shown to improve children's adjustment and
      reduce problem behaviour; however, little research has addressed outcomes for
      Indigenous families. The aim of this project was to assess the impact and
      cultural appropriateness of a parenting programme tailored for Indigenous
      families, an adaptation of the evidence-based Group Triple P - Positive Parenting
      Program. METHODS: A repeated measures randomised group design methodology was
      used, comparing the intervention with a waitlist control condition pre- and post
      intervention, with a 6-month follow-up of the intervention group. RESULTS:
      Parents attending Group Triple P reported a significant decrease in rates of
      problem child behaviour and less reliance on some dysfunctional parenting
      practices following the intervention in comparison to waitlist families. The
      programme also led to greater movement from the clinical range to the non-clinic
      range for mean child behaviour scores on all measures. Effects were primarily
      maintained at 6-month follow-up. Qualitative data showed generally positive
      responses to the programme resources, content and process. However, only a small
      number of waitlist families subsequently attended groups, signalling the
      importance of engaging families when they first make contact, helping families
      deal with competing demands, and offering flexible service delivery so families
      can resume contact when circumstances permit. CONCLUSIONS: This study provides
      empirical support for the effectiveness and acceptability of a culturally
      tailored approach to Group Triple P conducted by Child Health and Indigenous
      Health workers in a community setting. The outcomes of this trial may be seen as
      a significant step in increasing appropriate service provision for Indigenous
      families and reducing barriers to accessing available services in the community.

PMID- 17535172
TI  - Parent-initiated oral corticosteroid therapy for intermittent wheezing illnesses
      in children: systematic review.
AB  - AIM: Intermittent wheezing illnesses, which include viral-associated wheeze and
      asthma, are among the most common reasons for children to present urgently to a
      doctor. The objectives of this systematic review were to assess the benefits and
      harmful effects of parent-initiated oral corticosteroids (PIOCS) in the
      management of intermittent wheezing illness in children. METHODS: The Cochrane
      Airways Group Specialised Register, The Cochrane Controlled Trials Register
      (CENTRAL), MEDLINE, EMBASE, LILACS, Web of Science and Dissertation Abstracts
      were searched. Only randomised clinical trials studying patients aged between 1
      and 18 years, with an intermittent wheezing illness were included. RESULTS: From
      572 original citations, a total of two randomised clinical trials (303 randomised
      participants) were included. The quality of the included trials was high;
      however, marked clinical heterogeneity precluded a meta-analysis. The two trials
      did not find evidence that PIOCS are associated with a benefit in terms of
      hospital admissions, unscheduled medical reviews, symptoms scores, or
      bronchodilator use. CONCLUSION: Limited current evidence is available and it is
      inconclusive regarding the benefit from PIOCS therapy in the treatment of
      intermittent wheezing illnesses in children. Oral corticosteroids have a clearly
      defined role in the management of acute asthma in the hospital setting.
      Therefore, it is reasonable for clinicians to recommend PIOCS when (i) the child
      has a history of severe acute asthma; and (ii) the parents are able to assess
      asthma status. However, widespread use of PIOCS cannot be recommended until the
      benefits and harms can be clarified further.

PMID- 17535173
TI  - Parent-initiated oral corticosteroid therapy for acute asthma: a survey of
      current practice.
AB  - AIM: To determine (i) the proportion of doctors who recommend parent-initiated
      oral corticosteroids (PIOCS) for acute asthma; and (ii) the proportion of parents
      who have received this advice. METHODS: (i) An internet-based survey of doctors
      involved in the care of children with asthma; and (ii) a questionnaire-based
      survey of parents of children aged 4-13 years who were identified from a random
      sample of primary schools within the Barwon region of Victoria. RESULTS: Eight
      five per cent (95% confidence interval 80.0-89.1%) of responding doctors reported
      recommending PIOCS to parents of children with asthma. However, only 16.5% (95%
      confidence interval 14.2-18.7%) of parents of children with recent asthma
      symptoms report that they have received such advice. CONCLUSION: The majority of
      responding doctors involved in the care of children with asthma report
      recommending PIOCS to parents. By contrast, a minority of parents of children
      with asthma report that they have received such advice.

PMID- 17535174
TI  - Post-streptococcal glomerulonephritis in Sydney: a 16-year retrospective review.
AB  - AIM: Post-streptococcal glomerulonephritis (PSGN) is a frequent cause of acute
      nephritis in children. Numerous studies have described PSGN in high-risk
      populations yet few data describing PSGN in a low-incidence population exist.
      This study aimed to describe the epidemiology, clinical manifestations,
      diagnosis, complications and outcomes of PSGN in an urban Australian population.
      METHODS: A 16-year retrospective review of case notes and laboratory data was
      conducted at a tertiary Sydney paediatric hospital. RESULTS: Thirty-seven
      children were treated for PSGN with a mean age of 8.1 years (range 2.6-14.1
      years). Twenty-eight subjects (75.7%) had a history of a recent upper respiratory
      tract or skin infection. Hypertension and/or oedema was present in 29 subjects
      (78.4%). Streptococcal pharyngitis was identified as the likely source in 17
      subjects (45.9%). Skin infections occurred less frequently. Antibodies against
      streptolysin O, streptokinase or deoxyribonuclease B were elevated when a single
      titre was measured in 35 subjects (94.6%). Thirty subjects (81.1%) developed
      renal impairment (median peak creatinine, 95 micromol/L, range 39-880
      micromol/L). No correlation was demonstrated between peak creatinine, age,
      ethnicity, streptococcal titres and serum complement levels. The mean length of
      admission was 8.2 days. Seven subjects (18.9%) had a complicated course with
      three subjects requiring dialysis. Only one subject has ongoing renal
      dysfunction. CONCLUSION: Significant differences are seen in a low-incidence
      urban Australian population with PSGN when compared with endemic or epidemic
      disease in high-risk populations. The higher rates of complications that were
      seen compared with previously studied populations need further clarification.

PMID- 17535175
TI  - Diverging trends for lower respiratory infections in non-Aboriginal and
      Aboriginal children.
AB  - AIM: To investigate temporal trends in admission rates for acute lower
      respiratory infections (ALRI) in a total population birth cohort of non
      Aboriginal and Aboriginal children. METHODS: Retrospective analysis of linked
      population-based data using the Western Australian Data Linkage System. All
      singleton live births in Western Australia between 1990 and 2000 were included.
      Hospital admission rates per 1000 live births for ALRI before age 2 years and
      linear time trends for ALRI admission rates were investigated. RESULTS: ALRI
      admission rates were 7.5 (95% confidence interval (CI) 7.2-7.7) times higher in
      Aboriginal than non-Aboriginal children (337 vs. 45 per 1000 live births);
      pneumonia rates were 13.5 (95% CI 12.8-14.4) times higher and bronchiolitis rates
      were 5.8 (95% CI 5.3-6.0) times higher. ALRI admission rates rose in non
      Aboriginal children (<12 months, 6%/year, P<0.002; 12-23 months, 11%/year,
      P<0.001) but declined in Aboriginal children aged 12-23 months (4%/year,
      P=0.003). Bronchiolitis rates rose in all children, especially non-Aboriginal
      infants aged <12 months (13%/year, P<0.001), while pneumonia rates rose in non
      Aboriginal children but declined in Aboriginal children. Declines in bronchitis
      and asthma were also noted. CONCLUSION: There has been an increase in incidence
      of bronchiolitis before age 12 months. For children aged 12-23 months a
      diagnostic shift from asthma and bronchitis to bronchiolitis and changes in
      health service utilisation are likely explanations for diverging temporal trends.
      The continuing disparity between Aboriginal and non-Aboriginal children needs to
      be addressed and appropriate preventative measures for ALRI, and in particular
      bronchiolitis, are urgently needed.

PMID- 17535176
TI  - Association between the family environment and television viewing in Australian
      children.
AB  - AIM: To describe the time children spend watching television (TV) and to assess
      associations between TV viewing time, the family environment and weight status.
      METHODS: Parents reported the amount of time children watched TV/video both for
      'the previous school day' and 'usually' and described aspects of the family
      environment influencing TV access as part of a large cross-sectional study in the
      Barwon South-western region of Victoria, Australia. Child weight status was based
      on measured height and weight. All data were collected in 2003/2004. RESULTS: A
      total of 1926 children aged 4-12 years participated. Parent-reported mean +/- SE
      TV time for the previous school day was 83 +/- 1.5 min. Children who lived in a
      family with tight rules governing TV viewing time (22%), or who never watched TV
      during dinner (33%), or had only one TV in the household (23%) or had no TV in
      their bedroom (81%) had significantly less TV time than their counterparts.
      Overweight or obese children had more TV time than healthy weight children 88 +/-
      2.9 versus 82 +/- 1.7 min per day (P=0.04). They were also more likely to live in
      a household where children had a TV in their bedroom than healthy weight children
      (25% vs. 17%, P<0.001). CONCLUSION: Strategies to reduce TV time should be
      included as part of broader strategies to prevent childhood obesity. They should
      include messages to parents about not having a TV in children's bedrooms,
      encouraging family rules restricting TV viewing, and not having the TV on during
      dinner.

PMID- 17535177
TI  - Do paediatricians provide brief intervention for adolescents who smoke?
AB  - AIMS: This study aimed to describe the self-reported practice of paediatricians
      in brief interventions for adolescents who smoke. We also aimed to compare
      practice with confidence, skills and knowledge of brief intervention and nicotine
      replacement therapy after a targeted training programme. METHODS: Medical staff
      at The Children's Hospital at Westmead completed a questionnaire of clinical
      practice and confidence in brief intervention for smoking cessation. Data were
      analysed comparing self-reported practice with confidence, skill and knowledge of
      brief interventions, based on Fiore's 5A's approach (Ask about smoking at every
      opportunity, Assess willingness to quit, Advise patients to quit smoking, Assist
      quit attempts and Arrange follow up). RESULTS: Fifty-seven clinicians completed
      questionnaires, 55 (96%) recognised the importance of asking adolescents about
      smoking. Thirty-one (54%) identified adolescent smokers all or most of the time,
      increasing to 50 (88%) if their presenting condition was associated with smoking.
      Twenty-five (44%) clinicians assessed the stage of change, 33 (58%) advised the
      adolescent to quit smoking, nine (16%) assisted quit attempts and 10 (17.5%)
      arranged follow up. Clinicians more confident in brief intervention skills,
      motivational interviewing and relapse prevention were more likely to use the 5A's
      (P<0.05). Training increased clinician's confidence in brief intervention skills
      and knowledge of nicotine replacement therapy (P<0.01); however, there was no
      statistically significant change in clinical practice 1 month post training.
      CONCLUSION: Training paediatricians in brief intervention skills, motivational
      interviewing and relapse prevention can increase the use of 5A's brief
      intervention in clinical practice, potentially increasing quit attempts in
      adolescents who smoke.

PMID- 17535178
TI  - Practice variation in initial management and transfer thresholds for infants with
      respiratory distress in Australian hospitals. Who should write the guidelines?
AB  - AIM: In Australian hospitals: (i) to identify current practices in the initial
      oxygen management of infants with respiratory distress; (ii) to identify factors
      important in deciding to transfer an infant; and (iii) to identify thresholds for
      transfer. METHODS: All Australian hospitals with: >200 registered deliveries, a
      special care unit (SCU) or neonatal intensive care unit (NICU), and at least one
      paediatrician were surveyed in 2004 (n=176). The questionnaire sought information
      on the initial oxygen management and factors important in deciding to transfer.
      Three scenarios were also used to identify thresholds for pH, carbon dioxide and
      oxygen levels at which transfer should occur. Responses from SCU were compared
      with those from NICU. RESULTS: 15/19 (79%) NICUs and 118/157 (75%) SCUs
      responded. Initial oxygen management varies widely among SCUs and NICUs. NICUs
      set significantly lower saturation (SaO(2)) targets in two of the three
      scenarios. NICUs are statistically significantly more likely to regard 'Medical
      Staff Experience' and 'Time to Nearest NICU' as important compared with SCUs
      (P<0.05). NICUs would 'Probably' and 'Definitely Transfer' infants at
      significantly lower oxygen levels in all three cases (P<0.05). SCUs are
      significantly less likely to transfer babies with pH of <7.25 compared with
      NICUs. There was no difference between the centres for CO(2) level. CONCLUSION:
      The wide variation that exists between nurseries in the initial management of
      infants with respiratory distress and in the thresholds for transfer strongly
      suggests the need for the development of practice guidelines.

PMID- 17535179
TI  - Effect of number of BCG vaccination on tuberculin induration size.
AB  - AIM: The aim of this study is to interpret purified protein derivative (PPD)
      induration sizes with respect to the number of Bacillus Calmette-Guerin (BCG)
      scars. METHODS: We have considered 1879 school children between the ages of 7 and
      14 years from seven primary schools in Kocaeli, Turkey. Children were injected
      with 5TU 0.1 mL PPD and induration sizes were measured at 72 h. Number of BCG
      scars, PPD application dates and induration sizes were recorded for each pupil.
      This study was also evaluated further for 312 households. RESULTS: The mean
      diameter of PPD induration size for 0, 1, 2 and 3 BCG vaccination scars were 1.43
      mm (95% confidence interval (CI): 0.84-2.02), 6.39 mm (95% CI: 5.91-6.87), 10.46
      mm (95% CI: 10.04-10.88) and 11.35 mm (95% CI: 9.36-13.34), respectively.
      Furthermore, 90% and 95% percentiles of PPD induration 0, 1, 2 and 3 vaccinations
      were 10 and 12 mm, 16 and 19 mm, 17 and 19 mm and 19.2 and 20 mm, respectively.
      There was evidence for a linear trend across from 0 to 3 BCG vaccinations,
      indicating that mean induration size increases with the number of vaccination
      scars. The size of indurations directly correlated with the number of vaccination
      scars, PPD induration size of children with no vaccination scar was quite small
      and it was generally less than 5 mm. CONCLUSION: This study shows the importance
      of the number of BCG scars in the determination of PPD induration size limit when
      tuberculosis infection is evaluated.

PMID- 17535180
TI  - Developmental outcomes at the age of two years for very premature babies managed
      with nasal prong continuous positive airway pressure.
AB  - AIMS: To describe the developmental progress of very premature babies at the age
      of 2 years, who were managed in an era where nasal prong continuous positive
      airway pressure (CPAP) was the preferred method for the management of initial
      respiratory disease. METHODS: Two groups of very premature babies of <32 weeks
      gestation were compared, the first being managed with an intubation and mandatory
      ventilation approach, and the second being managed with a CPAP approach. The
      groups are compared with regard to the presence of brain injury, retinopathy and
      requiring discharge home on oxygen and then at 2 years, for language impairment,
      non-ambulatory cerebral palsy and significant developmental delay. The study is
      designed as an audit of data collected prospectively and longitudinally for
      babies born from 1998 to 2002. RESULTS: A significant number of babies were
      successfully managed on CPAP in the second era and significantly fewer received
      post-natal steroids. The number being discharged home on oxygen, brain injury and
      retinopathy were similar in the two groups. Developmental outcome assessed at 2
      years of age was the same in both eras. CONCLUSIONS: A CPAP approach to the
      management of initial respiratory disease in premature babies of less than 32
      weeks gestation at birth is associated with no measurable developmental advantage
      or disadvantage at 2 years of age.

PMID- 17535181
TI  - Changing pattern of child bicycle injury in the Bay of Plenty, New Zealand.
AB  - AIM: To determine if helmet laws and safety campaigns have had an impact on
      bicycle injuries in children. METHODS: A comparison of the number of bicycle
      injuries presented to Whakatane Hospital's Emergency Department in the period
      1982-1986 to the period July 1998-December 2005. RESULTS: In the first period
      there were 597 per 100,000 presentations per annum which increased to 890 per
      100,000 per annum in the later period (P<0.01). Fractures increased from 115 to
      234 per 100,000 per annum respectively (P=0.02). Injuries from a collision with a
      moving motor vehicle decreased from 72 to 30 per 100,000 per year and of those
      the proportion of serious head injuries dropped from 65% to 33%. There were four
      deaths in the earlier period but none in recent years. CONCLUSIONS: Injuries from
      bicycle use have increased but there has been a marked reduction in collisions
      with motor vehicles. This is a result of the changing use of bicycles by
      children.

PMID- 17535182
TI  - Collaborative decision-making for extreme premature delivery.
AB  - A multidisciplinary workshop with parent/consumer involvement was held to
      determine a consensus in the difficult arena of perinatal care of women and
      babies at the borderlines of viability. Interactive forums produced consensus
      statements following an extensive consultation process. A grey zone between 23(0)
      and 25(6) weeks of gestation was identified and agreed upon. In this grey zone,
      while there was an increasing obligation to treat, it was acceptable not to
      initiate intensive care following appropriate counselling with parents. Important
      areas identified before birth, were continuing communication between the
      perinatal team and parents, a review of choice with continued counselling,
      decision support and empathy. The process must be transparent, open and honest,
      using the most relevant up to date outcome data in a collaborative framework.

PMID- 17535183
TI  - Consensus statement on perinatal care.
AB  - While there is general agreement with the framework of the consensus statements,
      it is at the margins of the 'grey zone', particularly at 23 weeks of gestation,
      that practice in other states appears to differ from practice in New South Wales
      (NSW)/Australian Capital Territory (ACT). This is evidenced by the lower regional
      survival in NSW/ACT at 23 weeks compared with other contemporaneous regional
      Australian cohorts, reflecting the discouragement of active intervention in
      NSW/ACT at this gestation. At the other end of the 'grey zone', surely active
      intervention, including prenatal transfer to a tertiary obstetric centre, should
      always be given to an otherwise uncomplicated 25-week infant? At any of these
      gestations, where infants survive, the majority are not severely disabled,
      leading us in this state to support initiation of intensive care to infants of
      marginal gestations where informed parents wish us to do so. The consensus
      conference questions and response rates by professional group should be published
      in full.

PMID- 17535184
TI  - Cows milk protein enteropathy and granulomatous duodenitis in a newborn.
AB  - Cow's milk protein enteropathy is a symptom complex that composed of severe
      diarrhoea and malnutrition. This disorder is caused by non-immunoglobulin E
      mediated food allergy. Its clinical features and natural course have been
      explained in many reports, of different types of cow's milk and soy reactions. In
      the present article, we describe a newborn patient who presented with chronic
      diarrhoea and failure to thrive diagnosed as cow's milk protein enteropathy. The
      duodenal biopsy revealed granulomatous duodenitis which has not been described
      before. Her clinical and pathological findings responded well to cow's milk
      elimination. We suggest that food allergies should be considered in differential
      diagnosis of patients with chronic diarrhoea and failure to thrive.

PMID- 17535185
TI  - Ingested magnets and gastrointestinal complications.
AB  - Multiple magnet ingestion is an unexpected health hazard in children that can
      lead to significant gastrointestinal morbidity. The magnets are attracted to each
      other across the bowel wall and this may lead to pressure necrosis, resulting in
      perforation, fistula formation, and/or intestinal obstruction. We report herein a
      case of small bowel obstruction following ingestion of two magnets. The public
      and clinicians should be aware of the health hazard of such devices.

PMID- 17535186
TI  - Botulinum neurotoxin A: an unusual systemic effect.
AB  - Systemic effects from Botulinum neurotoxin A are uncommon but can have serious
      consequences. We report the case of a boy with severe cerebral palsy who
      developed deterioration in respiratory and oromotor function following repeated
      injections of Botulinum neurotoxin A. Caution is needed in using this treatment
      in children with severe cerebral palsy and pseudobulbar palsy.

PMID- 17535187
TI  - Single or double bubble: sign of trouble! Congenital pyloric atresia: report of
      two cases and review of literature.
AB  - Congenital pyloric atresia is a very rare anomaly. It can occur as an isolated
      anomaly and can be associated with other conditions such as aplasia cutis
      congenital/epidermolysis bullosa or multiple intestinal atresias. We present two
      cases of congenital pyloric atresia, solitary air bubble on X-ray abdomen being
      pathognomonic sign of pyloric atresia. However, it might present with an
      intermittent double bubble sign.

PMID- 17535188
TI  - Is there still a place for endotracheal adrenaline in neonatal resuscitation?

PMID- 17535189
TI  - An unusual congenital presentation of infantile digital fibromatosis.

PMID- 17535191
TI  - Solar keratosis: epidemiology, pathogenesis, presentation and treatment.
AB  - Solar keratosis is a common problem encountered by dermatologists, particularly
      in Australia. Solar keratosis is most commonly found on sun-exposed areas such as
      the scalp, face and forearms. UV radiation is thought to be the major
      aetiological factor, with age, immunosuppression and human papillomavirus being
      important contributing factors. Solar keratosis usually presents as a discrete,
      variably erythematous and irregular lesion with a scaly surface. Although the
      exact rate of malignant transformation to squamous cell carcinoma is unknown, the
      majority of squamous cell carcinomas appear to arise from within solar keratosis.
      For this reason, solar keratosis is commonly treated and, consequently, an
      increasing number of therapeutic options is now available. Traditional therapies,
      such as liquid nitrogen cryotherapy, are still popular, but newer choices, such
      as photodynamic therapy and imiquimod cream, are now providing further options
      with similar efficacy and superior adverse effect profiles, albeit at a higher
      cost.

PMID- 17535192
TI  - Prospective study to assess general practitioners' dermatological diagnostic
      skills in a referral setting.
AB  - A prospective study was conducted to assess general practitioners' diagnostic
      skills in a referral setting. The primary objective was to identify general
      practitioners' strengths and weaknesses in diagnosing a broad spectrum of skin
      conditions. The diagnoses of 315 skin conditions made by 165 general
      practitioners were compared with a reference standard. The reference standard was
      made up of 73 histopathological diagnoses, 119 dermatologists' clinical diagnoses
      and 123 dermatologists' diagnoses plus follow up. The diagnoses assigned by
      referring general practitioners were consistent with dermatologists' clinical
      diagnoses and histology (where available) in 57% of cases. General practitioners
      made the correct diagnosis in 44% of cases when compared with histopathology.
      General practitioners were generally good at diagnosing conditions such as acne,
      warts, rosacea, molluscum contagiosum, vitiligo and skin tags. The proportion of
      correct diagnoses for premalignant and malignant skin tumours was 47%, and that
      of skin rashes requiring a diagnosis was 44%. Further education of general
      practitioners would help to improve their diagnostic skills in certain skin
      conditions.

PMID- 17535193
TI  - Allergy to tea tree oil: retrospective review of 41 cases with positive patch
      tests over 4.5 years.
AB  - Tea tree oil use is increasing, with considerable interest in it being a
      'natural' antimicrobial. It is found in many commercially available skin and hair
      care products in Australia. We retrospectively reviewed our patch test data at
      the Skin and Cancer Foundation Victoria over a 4.5-year period and identified 41
      cases of positive reactions to oxidized tea tree oil of 2320 people patch-tested,
      giving a prevalence of 1.8%. The tea tree oil reaction was deemed relevant to the
      presenting dermatitis in 17 of 41 (41%) patients. Of those with positive
      reactions, 27 of 41 (66%) recalled prior use of tea tree oil and eight of 41
      (20%) specified prior application of neat (100%) tea tree oil. Tea tree oil
      allergic contact dermatitis is under-reported in the literature but is
      sufficiently common in Australia to warrant inclusion of tea tree oil, at a
      concentration of 10% in petrolatum, in standard patch-test series. Given tea tree
      oil from freshly opened tea tree oil products elicits no or weak reactions,
      oxidized tea tree oil should be used for patch testing.

PMID- 17535194
TI  - Microsporum canis: report of a primary school outbreak.
AB  - Microsporum canis is the causative organism in less than 10% of all tinea capitis
      infections in the UK. Transmission is generally via contact with an infected
      family pet and there are only rare reports of case clustering. This article
      describes an outbreak of M. canis in a primary school classroom demonstrating
      human-to-human spread from an index case who was presumed to have acquired the
      infection prior to arriving in the UK. There was no suggestion of clinical
      improvement following 4 weeks of oral terbinafine 125 mg daily and treatment was
      changed to griseofulvin. The Health Protection team screened class members and
      confirmed cases (either clinically or mycologically) were also treated with
      griseofulvin 10-20 mg/kg/day for 10 weeks. Classmates and siblings of classmates
      were recommended to use selenium sulphide or ketoconazole-containing shampoo
      twice weekly.

PMID- 17535195
TI  - Cutis verticis gyrata: three cases with different aetiologies that demonstrate
      the classification system.
AB  - Cutis verticis gyrata describes a scalp condition where there are convoluted
      folds and deep furrows that resemble the surface of the cerebral cortex. We
      report three cases of cutis verticis gyrata that demonstrate the current
      classification structure. The first case is the most commonly described primary
      non-essential acquired form, appearing in the scalp of an 11-year-old girl with
      mental retardation. The second case is the primary non-essential congenital form,
      presenting at birth in a baby with Noonan's syndrome. An association between
      cutis verticis gyrata and Noonan's syndrome has been rarely described. The third
      case illustrates secondary cutis verticis gyrata, occurring in a 27-year-old man
      with discoid eczema.

PMID- 17535196
TI  - Use of infliximab in pyoderma gangrenosum.
AB  - A 57-year-old man, with a 2-year history of Crohn's disease, presented with a
      rapidly progressive abdominal ulcer. It was clinically and histologically
      consistent with pyoderma gangrenosum but it did not respond to either high-dose
      oral prednisolone or intravenous hydrocortisone. Infliximab resulted in an early,
      dramatic and sustained improvement. His bowel symptoms, which flared a few weeks
      prior to the onset of pyoderma gangrenosum, only partially improved. Despite six
      infliximab infusions, the inflammatory bowel disease is poorly controlled,
      whereas the pyoderma gangrenosum remains healed.

PMID- 17535197
TI  - Lichen striatus following solarium exposure.
AB  - Two cases of lichen striatus occurring after solarium exposure are presented.
      Both patients were adult females who regularly attended a solarium prior to the
      development of their skin lesions. A 19-year-old woman attended the solarium
      twice weekly for 8 weeks prior to the appearance of lichen striatus on the chest
      and epigastrium. The condition resolved completely with the twice daily
      application of calcipotriol ointment for 6 months. The second patient, a 40-year
      old woman, attended the solarium once weekly for 3 months before lichen striatus
      developed on the abdomen. She was treated with clobetasol propionate ointment,
      calcipotriol ointment and intralesional triamcinolone acetonide and the eruption
      cleared 7 months after onset. The histopathological picture in both patients
      supported a diagnosis of lichen striatus.

PMID- 17535198
TI  - Iododerma following sitz bath with povidone-iodine.
AB  - A 50-year-old man developed numerous pustules and bullae on the trunk and limbs
      15 days after anal fissure surgery. The clinicopathological diagnosis was
      iododerma induced by topical povidone-iodine sitz baths postoperatively. Complete
      resolution occurred within 3 weeks using systemic corticosteroids and forced
      diuresis.

PMID- 17535199
TI  - Sweet's syndrome associated with cellulitis.
AB  - A 38-year-old woman developed an acute, painful cutaneous eruption on her lower
      legs, neck, chest and fingers while receiving a number of oral and intravenous
      antibiotics for left leg cellulitis caused by trauma. Clinically and
      histopathologically, she was diagnosed with Sweet's syndrome with typical
      pseudovesicular skin changes in conjunction with erythema nodosum-like lesions on
      her lower legs. She responded quickly to oral prednisolone. We propose
      Staphylococcal cellulitis as a cause of Sweet's syndrome.

PMID- 17535200
TI  - Trichodysplasia spinulosa associated with chemotherapy for acute lymphocytic
      leukaemia.
AB  - We report two boys with trichodysplasia spinulosa associated with chemotherapy
      for acute lymphocytic leukaemia. Trichodysplasia spinulosa is a cutaneous viral
      infection of immunosuppressed patients that causes abnormal hair follicle
      maturation. Our patients presented with widespread papules, some extruding a
      central keratin spicule, which were most prominent on the face. Histopathology
      demonstrated hair follicles dilated by a proliferation of large eosinophilic
      cells containing numerous abnormal trichohyaline granules. Electron microscopy in
      case 1 revealed 30-nm viral particles in the stratum corneum consistent with a
      papovavirus. In case 1, the eruption persisted despite topical salicyclic acid
      4%, ammonium lactate 17.5%, tretinoin 0.05% and oral acitretin. However, it
      resolved once the patient's immune function returned to normal (total duration of
      2 years). In case 2, the eruption spontaneously resolved after 9 months. This
      case report discusses the characteristic clinicopathological features of
      trichodysplasia spinulosa and, for the first time, follows the condition's
      natural history.

PMID- 17535201
TI  - Unusual case of lymphoedema in a morbidly obese patient.
AB  - A morbidly obese 57-year-old woman presented with dermatological complications of
      obesity including cellulitis and severe localized lymphoedema of the right leg.
      There were two large pedunculated masses on the right lateral thigh with early
      involvement of the left and overlying skin changes of chronic lymphoedema. Our
      patient's condition is clinically consistent with a new entity recently described
      in the surgical pathology literature as massive localized lymphoedema.

PMID- 17535202
TI  - Heterozygous prothrombin gene mutation associated with livedoid vasculopathy.
AB  - A 53-year-old woman presented with a chronic history of recurrent, painful
      ulcers, predominantly involving her lower legs. Both her clinical picture and
      histopathological findings were consistent with a diagnosis of livedoid
      vasculopathy, although she did have unusual findings of deep tender nodules and
      the presence of lesions over her elbows. Multiple investigations were undertaken,
      the only abnormality being a heterozygous mutation of the prothrombin G2021A
      gene. Although various coagulopathic states have been associated with livedoid
      vasculopathy, the finding of an associated prothrombin gene mutation is quite
      rare. Warfarin has ameliorated the clinical course when anti-inflammatory drugs
      and other anticoagulants were unhelpful.

PMID- 17535203
TI  - Rapid onset bilateral palmar keratoderma in a psoriasis patient wearing
      orthopaedic hand splints.
AB  - A 37-year-old man with a history of chronic stable plaque psoriasis fractured
      both hands during a fall on his outstretched hands. Ten days later, following
      surgery and the application of tight fitting orthopaedic hand splints, the
      splints were removed because of a 7-day history of painful and pruritic palms. It
      was evident that the injury to his hands and the firm application of his splints
      had resulted in a dramatic flare of his psoriasis. This manifested in two
      clinical forms that he had not developed previously. He had a strikingly
      symmetrical palmar keratoderma that had kobnerized maximally in the regions where
      the splints apposed his palms firmly. In addition, he had pustular psoriasis
      affecting the fingertips of both hands. After removal of the splints he responded
      to a combination of oral acitretin, and 6% coal tar and 6% salicylic acid in
      aqueous cream applied topically.

PMID- 17535204
TI  - Collision tumour of trichofolliculoma and basal cell carcinoma.
AB  - A 52-year-old woman presented with a 2-year history of a reddish nodule on the
      right nasolabial sulcus. Histopathological examination revealed that the nodule
      was composed of trichofolliculoma and basal cell carcinoma. There was no
      transitional zone between the two neoplasms. The diagnosis was made as a
      collision tumour of trichofolliculoma and basal cell carcinoma.

PMID- 17535205
TI  - Corn contact urticaria in a nurse.
AB  - A 33-year-old nurse presented with persistent hand dermatitis.
      Radioallergosorbent tests showed moderate to strong reactions to latex, avocado
      and banana. Despite avoidance of latex gloves, she failed to improve. Patch
      testing was negative. Prick testing showed a negative reaction to latex, but a
      strong reaction to corn, with relevance to cornstarch powder present in many
      medical examination gloves. She was diagnosed with corn contact urticaria,
      irritant contact dermatitis and type I hypersensitivity to latex fruits.

PMID- 17535206
TI  - Rosacea in a monozygotic twin.

PMID- 17535207
TI  - Exfoliative erythroderma, recurrent infections, generalized lymphadenopathy and
      hepatosplenomegaly in a newborn: Omenn syndrome.

PMID- 17535208
TI  - A simple intervention to improve safety in methotrexate prescribing.

PMID- 17535209
TI  - Pigmented osteoma cutis secondary to long-term tetracyclines.

PMID- 17535218
TI  - A current and online genodermatosis database.
AB  - Clinical dermatologists have great difficulty keeping abreast of research in
      genetic skin disease. This is because there is too much information, in too many
      places, and in an unfamiliar language. In this review we have simplified and
      tabulated our current knowledge of the genodermatoses. We hope this 'at a glance'
      online guide will help dermatologists apply research findings to clinical
      practice and give informed advice to patients.

PMID- 17535219
TI  - The role of fibroblasts in tissue engineering and regeneration.
AB  - Fibroblasts are mesenchymal cells that can be readily cultured in the laboratory
      and play a significant role in epithelial-mesenchymal interactions, secreting
      various growth factors and cytokines that have a direct effect on epidermal
      proliferation, differentiation and formation of extracellular matrix. They have
      been incorporated into various tissue-engineered products such as Dermagraft
      (Advanced BioHealing, La Jolla, CA, U.S.A.) and Apligraf (Novartis, Basel,
      Switzerland) and used for a variety of clinical applications, including the
      treatment of burns, chronic venous ulcers and several other clinical applications
      in dermatology and plastic surgery. In this article we review the cell biology of
      dermal fibroblasts and discuss past and current experience of the clinical use of
      cultured fibroblasts.

PMID- 17535220
TI  - Toll-like receptor agonists regulate beta-defensin 2 release in hair follicle.
AB  - BACKGROUND: Skin is constantly in contact with different pathogens, which are
      present in the environment. The hair follicle is particularly susceptible to this
      microbial invasion as it offers an easy way of access for microorganisms; for
      this reason it is equipped with defence mechanisms to avoid frequent infections.
      OBJECTIVES: To analyse the expression pattern of four different members of the
      toll-like receptor (TLR) family in murine hair follicles and to evaluate the
      effects of their activation by their specific microbiota-derived agonists, in
      terms of production of the antimicrobial peptide beta-defensin 2 (DEFB2).
      METHODS: TLR and DEFB2 protein expression was investigated by
      immunohistochemistry on murine skin samples. RESULTS: Murine hair follicle
      expresses TLR2, TLR4 and TLR5; agonists of TLR2, TLR4 and TLR5 but not of TLR9
      induced DEFB2 production in this compartment. The strongest DEFB2 expression was
      observed following TLR4 activation by lipopolysaccharide. CONCLUSIONS: Our data
      show that the hair follicle is equipped with TLR2, TLR4 and TLR5, and that these
      receptors are able to respond to microbial stimuli inducing the production of
      DEFB2 by epithelial cells. This immune response might be important in preserving
      the skin from microorganism infections.

PMID- 17535221
TI  - Effect of heat shock protein 47 on collagen accumulation in keloid fibroblast
      cells.
AB  - BACKGROUND: Keloid is characterized by excessive collagen accumulation, but the
      mechanism of keloid formation remains unknown, and none of the treatment
      modalities are consistently effective. Heat shock protein (HSP) 47, known as a
      collagen-specific molecular chaperone, plays a critical role in collagen
      biosynthesis. Our previous research has demonstrated that HSP47 is highly
      expressed in keloid compared with normal skin tissues, which indicates that there
      might be a close relationship between overexpression of HSP47 and excessive
      collagen accumulation in keloid formation. OBJECTIVES: To further investigate
      whether overexpression of HSP47 might promote excessive collagen deposition in
      keloid formation, we examined the alteration of intracellular and extracellular
      collagen expression, following inhibition of HSP47 expression in keloid
      fibroblast cells by the RNA interference technique. METHODS: Three constructed
      psiRNA-hH1neo plasmids, carrying three pairs of related HSP47-shRNA (small
      hairpin RNA), respectively, were transfected into keloid fibroblast cells and
      compared with three control groups. After transfection, the mRNA and protein
      expression of HSP47 and collagen type I were detected by quantitative real-time
      polymerase chain reaction and Western blot; the content of extracellular
      secreting collagen was assessed by hydroxyproline assay; and the MTT [3-(4, 5
      dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide] method was adopted to
      examine the proliferation of keloid fibroblast cells. RESULTS: Both the mRNA and
      protein levels of HSP47 in keloid fibroblast cells decreased dramatically 48 h
      after post-transfection of three related HSP47-shRNA plasmids, compared with
      control groups. Following the downregulation of HSP47, we found that the
      expression of intracellular and extracellular collagen was correspondingly
      reduced. On the other hand, the MTT assay showed that transfection of HSP47-shRNA
      plasmids did not influence the growth of keloid fibroblast cells. CONCLUSIONS:
      Combined with our previous histological results, we propose that overexpression
      of HSP47 in keloid fibroblast cells could induce excessive collagen accumulation
      by enhancing synthesis and secretion of collagen, which not only presents a
      possible mechanism of keloid formation, but also offers a therapeutic potential
      of RNA interference to HSP47 for the treatment of keloid and other
      fibroproliferative disorders.

PMID- 17535222
TI  - Effectiveness of the nursing programme 'Coping with itch': a randomized
      controlled study in adults with chronic pruritic skin disease.
AB  - BACKGROUND: The nursing programme 'Coping with Itch' aims at reducing itch and at
      helping patients with chronic pruritic skin diseases cope with itch. The
      programme consists of educational and cognitive behavioural interventions.
      Dermatology nurses carry out the programme, which supplements standard medical
      treatment given by a dermatologist, in individual sessions at a nurse clinic
      organized by the dermatology outpatient department. OBJECTIVES: To evaluate the
      effectiveness of the nursing programme 'Coping with Itch' in patients with
      chronic pruritic skin diseases. METHODS: A randomized controlled study was
      carried out. Patients with chronic pruritic skin diseases were randomly assigned
      to the intervention group or the control group. The intervention group received
      standard care from a dermatologist and nursing care according to the programme
      'Coping with Itch' for a mean of 2.9 visits. The control group received usual
      care from a dermatologist. Data collection took place at baseline, at 3 months
      (t1) and at 9 months (t2) after baseline. Most visits to the nurse clinic took
      place during the first 3 months of the study. Main outcome measures were the
      frequency and intensity of itching and scratching, itch-related coping, and skin
      related and general psychosocial morbidity. Secondary outcome measures were the
      number of visits to the dermatologist and the use of medication and ointments.
      Mann-Whitney tests and analyses of covariance were used to analyse differences
      between the two groups. RESULTS: Data on 29 patients in the intervention group
      and 36 patients in the control group were used in the analyses. A trend to
      significance (P = 0.07) was shown in the difference between the two groups in the
      frequency of itching and scratching at t1. A significant difference (P = 0.04)
      was shown between the two groups in catastrophizing and helpless itch-related
      coping at t1. No significant differences were revealed at t2 between the groups.
      Patients in the intervention group visited the dermatologist significantly less
      frequently during the intervention period than did control group patients.
      CONCLUSIONS: The nursing programme 'Coping with Itch' led to a reduction in the
      frequency of itching and scratching and to a reduction of catastrophizing and
      helpless coping in patients with chronic pruritic skin diseases during the period
      immediately following the intervention. We suggest further follow-up visits to
      the itch clinic to extend these results over a longer period.

PMID- 17535223
TI  - Rapid, severe repigmentation of congenital melanocytic naevi after curettage and
      dermabrasion: histological features.
AB  - BACKGROUND: Curettage and dermabrasion are effective in treating giant congenital
      melanocytic naevi (GCMN). We report two patients with rapid, severe postoperative
      repigmentation. To the best of our knowledge this is the first report on the
      histological features of such patients. OBJECTIVES: We wish to call attention to
      histological features that may cause rapid, severe repigmentation after curettage
      and dermabrasion of medium to giant CMN. PATIENTS/METHODS: From 1998 to 2002, we
      treated 23 patients with medium to giant CMN with curettage and dermabrasion.
      Patients being treated ranged in age from 1 month to 19 years. Histological
      samples were taken from the centre of naevi in all patients during surgery.
      Histological types were 12 intradermal and 11 compound. Follow-up after curettage
      lasted at least 3 years. RESULTS: Among our 23 patients only two showed
      repigmentation soon after surgery. Histological sections from these two patients
      indicated naevoid cells in the deep dermis along hair follicles or sebaceous
      glands. However, no such pigmented naevoid cells along hair follicles were
      observed in samples from patients successfully treated with curettage and
      dermabrasion with less repigmentation. CONCLUSIONS: Although we saw only two
      cases of repigmentation soon after curettage and dermabrasion, we suspect a
      correlation between pigmented naevoid cells around hair follicles and
      repigmentation. If histological sections of skin biopsies show pigmented cells
      along hair follicles in the deep dermis, other treatments such as total skin
      resection followed by skin grafting or tissue expansion may be better choices
      than curettage or dermabrasion.

PMID- 17535224
TI  - Should eye protection be worn during dermatological surgery: prospective
      observational study.
AB  - BACKGROUND: There is a potential risk of infection with blood-borne viruses if a
      doctor receives a blood splash to a mucous membrane. The quantification of facial
      contamination with blood has never been documented in the context of
      dermatological surgery. OBJECTIVES: (i) To identify the number of facial blood
      splashes that occur during skin surgery and to identify the procedures that
      present higher risks for the operator and assistant. (ii) To assess the provision
      of eye protection and attitudes to its use in dermatological surgery in the U.K.
      METHODS: (i) Prospective, observational study in the skin surgery suite of a U.K.
      teaching hospital assessing 100 consecutive dermatological surgery procedures,
      plus 100 consecutive operations in which an assistant was present. PRIMARY
      OUTCOME: number of face-mask visors with at least one blood splash. SECONDARY
      OUTCOMES: to identify if any of the following variables influenced the occurrence
      of a blood splash: grade of operator, site and type of procedure, and the use of
      electrocautery. (ii) A postal survey of all U.K.-based members of the British
      Society of Dermatological Surgery (BSDS) was conducted assessing facilities
      available and the attitudes of U.K.-based clinicians to the use of face masks
      during surgery. RESULTS: (i) In 33% of all surgical procedures there was at least
      one facial splash to the operator (range 1-75) and in 15% of procedures the
      assistant received at least one splash (range 1-11). Use of monopolar
      electrocautery was significantly less likely to result in splashes to the mask
      compared with bipolar electrocautery [odds ratio (OR) 0.04; 95% confidence
      interval (CI) 0.01-0.19]. Compared with the head/neck, operations on the body
      were significantly more likely to result in splashes to the mask (OR 6.52) (95%
      CI 1.7-25.07). The type of procedure and the status of the operator did not have
      a bearing on the likelihood of receiving a splash to the mask. (ii) From the
      survey, 33 of 159 (20.8%) of BSDS members had no face masks available and 54 of
      159 (34.0%) did not wear any facial protection while operating. The majority
      (53.5%) thought they received a splash in <or= 1% of procedures. CONCLUSIONS:
      There is a substantial risk of a splash of blood coming into contact with the
      face during dermatological surgery for both the operator and assistant,
      regardless of the procedure. The risk of receiving a blood splash to the face may
      be substantially underestimated by U.K.-based dermatologists. The use of
      protective eyewear is advisable at all times, but particularly when using bipolar
      electrocautery, or when operating on high-risk individuals.

PMID- 17535225
TI  - Erythema migrans: a reassessment of diagnostic criteria for early cutaneous
      manifestations of borreliosis with particular emphasis on clonality
      investigations.
AB  - BACKGROUND: Controversy exists about the relationship of borrelia infection with
      B-cell lymphomas because B-cell clonality has been identified in infiltrates that
      contained borrelia-specific DNA. Systematic clinicopathological,
      immunophenotypical and molecular pathological studies of early borreliosis are
      lacking. OBJECTIVES: (i) To clarify whether clonal B-cell populations are present
      already in early borreliosis of the skin (erythema migrans); (ii) to re-evaluate
      clinicopathological, immunophenotypical and molecular pathological criteria for
      diagnosis of erythema migrans. METHODS: Study of 34 patients with erythema
      migrans confirmed by polymerase chain reaction (PCR). Infiltrates were analysed
      by histopathological and immunohistochemical methods and multiplex PCR for clonal
      IgH rearrangements. RESULTS: Erythema migrans shows a broad spectrum of changes
      including sparse infiltrates of T lymphocytes, dense interstitial granulomatous
      infiltrates (CD68+), and pseudolymphomatous patterns with germinal centre
      formation. There were accompanying epidermal changes in 59% of patients, and
      plasma cells were an inconsistent finding. B cells were few when infiltrates were
      sparse, but increased disproportionately when infiltrates were dense. IgH
      rearrangement studies revealed one pseudo-oligoclonal, three pseudoclonal and
      three clonal infiltrates. Pseudoclonality was encountered when infiltrates
      contained only few B lymphocytes. CONCLUSIONS: Infiltrates in erythema migrans
      are dominated by T cells followed by CD68+ histiocytes and B lymphocytes. Plasma
      cells are an inconsistent finding. Pseudoclonality of IgH rearrangement is a
      result of infiltrates being sparse in B lymphocytes and represents a pitfall in
      molecular pathological diagnosis that can only be avoided by duplicate or
      triplicate tests. Incidental B-cell clonality may be encountered in patients with
      unequivocal erythema migrans and should not be interpreted as a malignant
      lymphomatous process induced by borrelia.

PMID- 17535226
TI  - Neuropeptides and their receptors in psoriatic skin in relation to pruritus.
AB  - BACKGROUND: Pruritus in patients with psoriasis has been reported to be more
      common than previously thought. OBJECTIVES: To determine the actual prevalence of
      pruritus in psoriasis according to severity of psoriasis and to verify the
      hypothesis of involvement of neuropeptides and their receptors in psoriatic
      pruritus. METHODS: We analysed questionnaire replies from 152 patients with
      chronic plaque-type psoriasis and we assayed the expression of neuropeptides and
      their receptors in lesional skin biopsies obtained from psoriatic patients with
      pruritus compared with those from psoriatic patients without pruritus,
      nonlesional skin of patients with pruritic psoriasis and normal controls by
      confocal laser scanning microscopy. RESULTS: Of the 152 patients with psoriasis,
      112 (73.7%) had pruritus, and these patients had a higher mean Psoriasis Area and
      Severity Index (PASI) score than psoriatic patients without pruritus. There was
      positive correlation between the PASI score and the intensity of pruritus.
      Keratinocytes in the psoriatic plaques of patients with pruritus showed
      consistently increased expression of substance P receptor (SPR), high-affinity
      nerve growth factor receptor (TrkA) and calcitonin gene-related peptide receptor
      (CGRPR). CONCLUSIONS: Pruritus is a common feature in psoriasis. Considering the
      well-known roles of neuropeptides in pathogenesis of both psoriasis and pruritus,
      increased SPR, TrkA and CGRPR may be involved in the pathogenesis of pruritus in
      psoriasis and in the severity of psoriasis.

PMID- 17535227
TI  - The absence of apoeccrine glands in the human axilla has disease pathogenetic
      implications, including axillary hyperhidrosis.
AB  - BACKGROUND: The existence of a third type of sweat gland in human axillary skin,
      the apoeccrine gland, with a capacity to produce much higher sweat output than
      the eccrine gland, was proposed from examination of microdissected glands.
      However, previous studies of axillary skin glands did not examine the entire
      individual glandular structure via serial sections and the markers used to
      identify the different glands gave conflicting results and, hence, the existence
      of the apoeccrine gland remains controversial. OBJECTIVES: To investigate human
      axillary sweat glands by serial section histology and immunofluorescence.
      METHODS: Human axillary sweat glands were investigated by serial sectioning of
      paraffin wax-embedded skin samples taken by biopsy from four male and six female
      volunteers (age range 20-35 years). Sections were examined by light microscopy
      and immunofluorescence, using antibodies to antigens reported to be markers for
      discriminating between eccrine and apocrine gland cells: CD15, CD44, S100 and
      human milk fat globulin. RESULTS: Light microscopy demonstrated that there were
      hair follicles and a mean +/- SD of 76 +/- 14 sweat glands cm(-2). Eccrine and
      apocrine glands were found to be present; however, no glands resembling the
      apoeccrine glands were detected. Both types of sweat gland exhibited signs of
      being active, with segments of the secretory coils displaying flattened cells and
      dilated glandular lumina; however, this dilation did not extend to obvious
      changes in the width of the gland. None of the eccrine glands exhibited evidence
      of the presence of apocrine cells or vice versa. Immunofluorescence markers were
      found not to be specific and did not discriminate between the different types of
      glands or demonstrate the presence of apoeccrine glands. CONCLUSIONS: This is the
      first time that serial sections of axillary skin have been examined by histology
      and immunofluorescence. The markers reported to discriminate between apocrine and
      eccrine glands were found to be nonspecific. No evidence of apoeccrine glands was
      found either by histology or by immunofluorescence.

PMID- 17535228
TI  - Genetic and epigenetic alterations in the differential diagnosis of malignant
      melanoma and spitzoid lesion.
AB  - BACKGROUND: The histopathological differentiation of malignant melanoma and Spitz
      naevus often presents diagnostic problems. OBJECTIVES: We aimed to find out
      applicable diagnostic parameters other than routine pathology. METHODS: The cases
      included conventional melanomas and Spitz naevi as well as atypical spitzoid
      lesions that had posed diagnostic difficulties. We examined hotspots of mutation
      in the BRAF, NRAS and HRAS genes by polymerase chain reaction-based direct
      sequencing. We also analysed DNA copy number aberrations and the methylation of
      CpG sequences in several cancer-related genes by utilizing a novel methylation
      specific multiplex ligation-dependent probe amplification method. RESULTS: Twenty
      three of 24 conventional melanomas showed at least one of the genetic and
      epigenetic alterations examined, although one acral melanoma did not show any
      alteration. By sharp contrast, 12 Spitz naevi with an unambiguous histopathology
      showed no or few chromosomal aberrations, no oncogene mutations and no
      methylation of CpG sequences. Of the 16 ambiguous spitzoid lesions, most of which
      were designated atypical Spitz tumour by one of the authors, all but one showed
      no mutations, no methylations and few copy number aberrations. However, three
      tumours showed copy number loss of the cyclin-dependent kinase inhibitor 2A gene
      (CDKN2A), an alteration observed frequently in melanomas but not found in
      conventional Spitz naevi. These results show that, although most atypical Spitz
      tumours do not differ from conventional Spitz naevi showing virtually no genetic
      and epigenetic aberrations, some cases may have chromosomal aberrations that
      include copy number loss of the CDKN2A gene. CONCLUSIONS: Genetic and epigenetic
      analyses may be useful as an additional diagnostic tool to distinguish between
      melanoma and Spitz naevus, and may help to define subgroups in atypical Spitz
      tumours.

PMID- 17535229
TI  - Recent trends in incidence of nonmelanoma skin cancers in the East of Scotland,
      1992-2003.
AB  - BACKGROUND: Historically, ascertainment of nonmelanoma skin cancer (NMSC) by
      cancer registries in the U.K. has been shown to be incomplete in several studies.
      However, recent evidence suggesting that almost all clinically diagnosed NMSCs
      are verified histologically, coupled with the increasing availability of
      electronic histopathology data to cancer registries, raises the possibility that
      this situation may have improved. OBJECTIVES: To assess recent trends in
      incidence of the main types of NMSC and carcinoma in situ (CIS) of the skin in
      Scotland. METHODS: The study was restricted to selected health board areas in the
      East of Scotland for which pathology data have been used routinely to support
      cancer registration since the early 1990s. Incident cases of squamous cell
      carcinoma (SCC) of the skin, CIS of the skin, and first ever basal cell carcinoma
      (BCC) were extracted from the Scottish Cancer Registry covering the period of
      diagnosis 1992-2003. Sex-specific, age-standardized and age-specific incidence
      rates were calculated for four consecutive 3-year periods of diagnosis. Estimated
      annual percentage changes (EAPCs) in incidence were calculated by Poisson
      regression modelling, with adjustment for age. The percentage distribution of
      SCC, BCC and CIS of the skin by anatomical site and sex was calculated for the
      period of diagnosis 1997-2003. RESULTS: The crude incidence of SCC for the period
      1995-97 was 34.7 per 100,000, comparable with the best existing Scottish estimate
      of 32.2 derived from a prospective survey in Glasgow during March 1995. Age
      adjusted rates of SCC, first ever BCC, and CIS of the skin have all increased
      significantly in both sexes between 1992 and 2003 (all P < 0.001), with EAPCs
      ranging in magnitude from +1.4% (first ever BCC in males) to +5.1% (CIS in
      males). The majority of lesions arose on the head and neck area, with the
      exception of CIS, which in females was more commonly located on the limbs.
      CONCLUSIONS: Ascertainment of NMSC has probably improved since the advent and use
      of electronic pathology data. Ongoing increases in age-adjusted incidence,
      combined with ageing of the population, will have major implications for the
      clinical workload associated with NMSC for the foreseeable future.

PMID- 17535230
TI  - Skin cancer trends in Northern Ireland and consequences for provision of
      dermatology services.
AB  - BACKGROUND: The incidence of skin cancer, both melanoma and nonmelanoma skin
      cancer (NMSC), is rising throughout the world. The evaluation of trends in skin
      cancer will allow better planning of the future development of skin cancer
      services. OBJECTIVES: Using data collected from the Northern Ireland Cancer
      Registry (NICR), the incidence of the three major cutaneous cancers, basal cell
      carcinoma (BCC), squamous cell carcinoma (SCC) and malignant melanoma (MM), was
      determined and the workload associated with their management assessed. METHODS:
      The records of patients with a first diagnosis of BCC, SCC or MM occurring
      between 1993 and 2002 were retrieved from the NICR database. The annual age- and
      sex-adjusted incidence rates of all three skin cancers were computed per 100 000
      person-years by direct standardization according to the European Standard
      Population. Trends in incidence were estimated by calculating the estimated
      annual percentage change using Microsoft Excel. For patients registered with the
      NICR as having BCC, SCC or MM, the number of pathological reports where malignant
      samples had been examined was counted and then summed to provide the number of
      specimens examined each year between 1993 and 2004. RESULTS: For all three
      cancers the age-specific rates for both males and females increased with age,
      except for MM in men aged 75 years and over, where the rates were seen to
      decrease. Over the 12-year period there was a 62% increase in the overall number
      of skin cancer samples processed by local pathology laboratories and a 20%
      increase in the number of patients. These data highlight the fact that many
      patients will have more than one skin cancer, which reinforces the benefit in
      collecting data for both patient and sample numbers in order to obtain a true
      reflection of the workload. The data have also shown that more affluent men and
      women have higher rates of BCC and MM than their less affluent counterparts.
      CONCLUSIONS: In view of the data presented it is clear that management of NMSC
      and MM will impose significant demands on services in the years ahead. This will
      impact on the entire multidisciplinary team. Future planning, in terms of
      manpower and resources, will prove essential if we are to remain in a position to
      manage our patients with these malignant tumours appropriately.

PMID- 17535231
TI  - Decreased human epidermal antigen-presenting cell activity after ultraviolet A
      exposure: dose-response effects and protection by sunscreens.
AB  - BACKGROUND: Ultraviolet (UV) exposure of human skin causes immunosuppression that
      contributes to the growth of skin cancer. The contribution of UVA in these
      processes is still a matter of debate. OBJECTIVES: The purpose of our study was
      first to find a dose-response effect of UVA exposure on human epidermal antigen
      presenting cell (APC) activity and to evaluate the protective capacity of two
      sunscreen formulations against a high level of acute UVA exposure. We also tried
      to evaluate the protective capacity afforded by the same sunscreens against UVA
      induced clinical changes such as redness and pigmentation. METHODS: The
      functional assessment of the alloantigen-presenting capacity of epidermal cells
      prepared from skin keratotome samples 3 days after UVA exposure was measured with
      a mixed epidermal cell-lymphocyte reaction (MECLR) in each healthy volunteer (n =
      16). Redness and pigmentation were assessed by chromametry 24 h after exposure to
      a single UVA dose. RESULTS: In vivo UVA exposure to 15, 30 and 60 J cm(-2)
      resulted in a dose-dependent decrease in purified allogeneic T cell (CD4+ T
      cells) proliferation induced by UVA-irradiated epidermal cells. The epidermal APC
      function was significantly decreased with a suberythemal exposure corresponding
      to 15 J cm(-2). The decrease, partial and not statistically different between 30
      and 60 J cm(-2), exhibits a plateau-response effect. There was no correlation
      between the decrease of the epidermal APC function and the intensity of erythema
      and persistent pigment darkening. Both sunscreen formulations strongly inhibited
      the UVA-induced reduction of MECLR at 90 J cm(-2). CONCLUSION: Our results
      clearly demonstrate that UVA impairs the APC activity of the epidermal cells and
      thus may contribute to UV-induced immunosuppression in humans. They also indicate
      that erythema and immunosuppression have different dose-response curves in the
      UVA range. The two sunscreen formulations afforded a significant protection
      against the decrease in epidermal APC activity induced by exposure to a high UVA
      dose (90 J cm(-2)).

PMID- 17535232
TI  - Miconazole as adjuvant therapy for oral lichen planus: a double-blind randomized
      controlled trial.
AB  - BACKGROUND: Topical steroids are the first choice for the treatment of oral
      lichen planus (OLP). Antifungal drugs are often employed together with them, to
      prevent secondary oral candidosis, although it has been suggested anecdotally
      that they can also be beneficial for OLP itself. OBJECTIVES: To compare the
      effect of clobetasol propionate with and without a topical antifungal drug
      (miconazole) on the symptoms and extension of OLP. METHODS: A randomized,
      parallel, double-blind trial was conducted at the Unit of Oral Medicine and
      Pathology of the University of Milan. Thirty-five outpatients with histologically
      proven OLP were randomly assigned to receive either clobetasol propionate and
      miconazole, or clobetasol propionate and placebo for 6 weeks. Primary outcomes
      included symptoms and extension of lesions; adverse effects were also recorded.
      RESULTS: All the patients who concluded the study (30 of 35) showed clinical and
      subjective improvement within 3 weeks. The addition of miconazole did not affect
      in a significant way the signs and symptoms of OLP. No cases of clinical
      candidosis were seen in the patients taking miconazole, while one-third (five of
      15) of the placebo group were affected. CONCLUSIONS: Although effective in
      preventing iatrogenic candidosis, the addition of miconazole to topical steroid
      treatment does not improve the efficacy of the therapy.

PMID- 17535233
TI  - Prevalence of physical symptoms of itch, pain and fatigue in patients with skin
      diseases in general practice.
AB  - BACKGROUND: Physical symptoms of skin diseases have been shown to negatively
      affect patients' wellbeing. Although insight into physical symptoms accompanying
      skin diseases is relevant for the management and treatment of skin diseases, the
      prevalence of physical symptoms among patients with skin diseases is a rather
      unexplored territory. OBJECTIVES: The goal of the present study was to examine
      the prevalence of physical symptoms of itch, pain and fatigue in patients with
      skin diseases. METHODS: On the basis of a systematic morbidity registration
      system in primary care, questionnaires were sent to 826 patients with skin
      diseases. Eventually, questionnaires from 492 patients were suitable for our
      analyses. RESULTS: Results indicated that patients with skin diseases
      particularly experience symptoms of itch and fatigue. Approximately 50% of all
      patients report experiencing these symptoms and about 25% experience these
      symptoms as relatively severe. Pain was relatively less frequently reported by
      23% of all patients, and was on average somewhat less intense. The physical
      symptoms showed relatively strong correlations with disease-related quality of
      life and self-reported disease severity. In contrast, only moderate correlations
      were found with comorbidity and demographic variables, which suggests that the
      physical symptoms of itch, pain and fatigue are consequences of the skin
      diseases. CONCLUSIONS: Itch and fatigue and, to a somewhat lesser extent, pain
      have a high prevalence among patients with skin diseases. Clinicians should be
      encouraged to carefully assess itch, pain and fatigue in patients with skin
      diseases, and where appropriate focus treatment to these symptoms.

PMID- 17535234
TI  - The use of a spectrophotometric intracutaneous analysis device in the real-time
      diagnosis of melanoma in the setting of a melanoma screening clinic.
AB  - BACKGROUND: Skin imaging devices to aid melanoma diagnosis have been developed in
      recent years but few have been assessed clinically. OBJECTIVES: To investigate if
      a spectrophotometric skin imaging device, the SIAscope, could increase a
      dermatologist's ability to distinguish melanoma from nonmelanoma in a melanoma
      screening clinic. METHODS: Eight hundred and eighty-one pigmented lesions from
      860 patients were prospectively assessed clinically and with the aid of the
      spectrophotometric device by a dermatologist. Assessment before and after
      spectrophotometric imaging was made and compared with histology, where available,
      or with the clinical diagnosis of a dermatologist with 20 years of experience.
      RESULTS: One hundred and seventy-nine biopsies were performed, with 31 melanomas
      diagnosed. Sensitivity and specificity for melanoma diagnosis before and after
      spectrophotometry were 94% and 91% vs. 87% and 91%, respectively, with no
      significant difference in the area under the receiver operating characteristic
      curves (0.932 and 0.929). CONCLUSIONS: Our study provides no evidence for the use
      of SIAscope by dermatologists to help distinguish melanoma from benign lesions.

PMID- 17535235
TI  - Planar xanthoma due to cholestasis in graft versus host disease.

PMID- 17535236
TI  - Dose-related reduction in allergen-specific T cells associates with clinical
      response of atopic dermatitis to methotrexate.

PMID- 17535237
TI  - The efficacy of oral treatment with pramiconazole in pityriasis versicolor: a
      phase II a trial.

PMID- 17535238
TI  - Erythema nodosum and eosinophilic oesophagitis: more than a chance association?

PMID- 17535239
TI  - Safety of calcineurin inhibitors in the management of lichen sclerosis.

PMID- 17535240
TI  - Interest in interests in photodynamic therapy.

PMID- 17535242
TI  - The Delphi panel in the economic evaluation of photodynamic therapy for actinic
      keratosis and basal cell carcinoma: poor results?

PMID- 17535243
TI  - Naevus sebaceus on the female breast accompanied with a tubular apocrine adenoma
      and a syringocystadenoma papilliferum.

PMID- 17535244
TI  - Palmoplantar pustulosis is not inevitably associated with antigliadin antibodies.

PMID- 17535245
TI  - Family history of psoriasis and age at disease onset in Italian patients with
      psoriasis.

PMID- 17535246
TI  - Stimulation of RNA polymerase II transcript cleavage activity contributes to
      maintain transcriptional fidelity in yeast.
AB  - The transcription elongation factor S-II, also designated TFIIS, stimulates the
      nascent transcript cleavage activity intrinsic to RNA polymerase II. Rpb9, a
      small subunit of RNA polymerase II, enhances the cleavage stimulation activity of
      S-II. Here, we investigated the role of nascent transcript cleavage stimulation
      activity on the maintenance of transcriptional fidelity in yeast. In yeast, S-II
      is encoded by the DST1 gene. Disruption of the DST1 gene decreased
      transcriptional fidelity in cells. Mutations in the DST1 gene that reduce the S
      II cleavage stimulation activity led to decreased transcriptional fidelity in
      cells. A disruption mutant of the RPB9 gene also had decreased transcriptional
      fidelity. Expression of mutant Rpb9 proteins that are unable to enhance the S-II
      cleavage stimulation activity failed to restore the phenotype. These results
      suggest that both S-II and Rpb9 maintain transcriptional fidelity by stimulating
      the cleavage activity intrinsic to RNA polymerase II. Also, a DST1 and RPB9
      double mutant had more severe transcriptional fidelity defect compared with the
      DST1 gene deletion mutant, suggesting that Rpb9 maintains transcriptional
      fidelity via two mechanisms, enhancement of S-II dependent cleavage stimulation
      and S-II independent function(s).

PMID- 17535247
TI  - Glutathione depletion in hippocampal cells increases levels of H and L ferritin
      and glutathione S-transferase mRNAs.
AB  - Glutathione plays an essential role in maintaining cellular redox balance,
      protecting cells from oxidative stress and detoxifying xenobiotic compounds.
      Glutathione depletion has been implicated in neurodegenerative disorders,
      including Alzheimer's and Parkinson's diseases. Cells of neuronal origin are
      acutely sensitive to glutathione depletion, providing an avenue for studying the
      mechanisms invoked for neuronal survival in response to oxidant challenge. We
      investigated the changes in mRNA profile in HT22 hippocampal cells following
      administration of homocysteic acid (HCA), a glutathione-depleting drug. We report
      that HCA treatment of HT22 murine hippocampal cells increases the levels of the
      mRNAs encoding at least three proteins involved in protection from oxidant
      injury, the mRNAs encoding heavy (H) and light (L) ferritin and glutathione S
      transferase (GST).

PMID- 17535248
TI  - Transcriptional regulation of the Drosophila ANT gene by the DRE/DREF system.
AB  - Adenine nucleotide translocase (ANT) is a crucial component in the maintenance of
      cellular energy homeostasis, as well as in the formation of the mitochondrial
      permeability transition pores. However, the molecular mechanisms regulating the
      expression of the ANT gene are poorly understood. In this study, we have
      identified three DNA replication-related elements (DRE; 5'-TATCGATA) in the 5'
      flanking region of the Drosophila ANT (dANT) gene. Gel-mobility shift analyses
      revealed that all three of the DREs were recognized by the DRE-binding factor
      (DREF). The site-directed mutagenesis of these DRE sites induces a considerable
      reduction in the activity of the dANT gene promoter in vitro. Analyses with
      transgenic flies harboring a dANT-lacZ fusion gene bearing the wild-type or
      mutant DRE sites showed that the DRE sites were required for the expression of
      dANT in vivo. We determined that the over-expression or knockdown of DREF exerts
      a regulatory effect on the activity of the dANT promoter. In addition, we
      observed the collapse of mitochondrial membrane potential in the eye imaginal
      discs in which DREF was over-expressed. These results show that DRE/DREF is a
      crucial regulator of dANT gene expression, and also suggest the possibility that
      cross-talk may occur between the DRE/DREF system and mitochondrial functioning.

PMID- 17535249
TI  - Critical role of the p400/mDomino chromatin-remodeling ATPase in embryonic
      hematopoiesis.
AB  - The SWI2/SNF2 family ATPase, p400/mDomino, is a core subunit of a large chromatin
      remodeling complex, and is currently suggested to play a unique function in
      histone variant exchange, a process by which chromatin structure is altered.
      Here, we investigated the role of p400/mDomino in mammalian development by
      generating mutant mice with a targeted deletion of the N-terminal domain of
      p400/mDomino (referred to as mDom(DeltaN/DeltaN)). The mDom(DeltaN/DeltaN) mice
      died on embryonic day 11.5 (E11.5), and displayed an anemic appearance and slight
      deformity of the neural tube. DNA microarray and quantitative RT-PCR analyses
      revealed that all of the embryonic globin genes and a globin chaperone gene were
      poorly expressed in the mDom(DeltaN/DeltaN) embryo and yolk sac on E8.5,
      indicating that primitive erythropoiesis was impaired. A hematopoietic colony
      assay indicated that the hematopoietic activity of the yolk sac was significantly
      blocked in the mutant mice. We also found that the expression of a limited set of
      Hox genes, including Hoxa7, Hoxa9 and Hoxb9, was drastically enhanced in the
      mDom(DeltaN/DeltaN) yolk sacs. These results suggest that p400/mDomino plays a
      critical role in embryonic hematopoiesis by regulating the expression of
      developmentally essential genes such as those in the Hox gene cluster.

PMID- 17535250
TI  - IFT-81 and IFT-74 are required for intraflagellar transport in C. elegans.
AB  - Intraflagellar transport (IFT) is essential machinery for biogenesis and
      maintenance of cilia in many eukaryotic and prokaryotic cells. A large number of
      polypeptides are known to be involved in IFT, but the physiological role of each
      component is not fully elucidated. Here, we identified a C. elegans orthologue of
      a Chlamydomonas reinhardtii IFT component, IFT-81, and found that its loss-of
      function mutants show an unusual behavioral property and small body size. IFT-81
      is expressed in sensory neurons, and localized at the base of cilia. The similar
      phenotypes with ift-81 mutants were also observed in several IFT mutants,
      suggesting these defects are caused by inability of IFT. We also demonstrated
      that IFT-81 interacts and co-localizes with IFT-74, which is another putative
      component of IFT. The ift-74 loss-of-function mutants showed phenocopies with ift
      81 mutants, suggesting IFT-81 and IFT-74 play comparable functions. Moreover, ift
      81 and ift-74 mutants similarly exhibited weak anomalies in cilia formation and
      obvious disruptions of transport in mature cilia. Thus, we conclude that IFT-81
      and IFT-74 coordinately act in IFT in C. elegans sensory cilia.

PMID- 17535251
TI  - Mutants carrying two sma mutations are super small in the nematode C. elegans.
AB  - Body size determination is critical for multicellular organisms; however, the
      mechanisms remain largely unknown. Mutations that alter body size were studied to
      solve the mechanisms, for example, in mouse, fruit fly and the nematode
      Caenorhabditis elegans. In C. elegans, a large mutant and several small body size
      (sma) mutants are known. Of the latter, sma-2, sma-3, sma-4, sma-6, dbl-1 and daf
      4 have a mutation in the components of the DBL-1/TGFbeta signal pathway, and sma
      5 in a MAP kinase homologue. We have constructed double mutants carrying two of
      such small body size mutations, sma-5 and sma-4 or sma-2. They are much smaller
      than either of the parental single mutants, indicating that the sma-5 gene
      functions independently of the DBL-1/TGFbeta pathway. We show that their body
      volumes are as small as 1/10 of that of the wild-type, and that the sizes of
      major organs are much reduced, by the methods previously developed by us. But the
      numbers of cells are not changed, suggesting that the cells are very small. These
      results highlight surprising flexibility of body size and cell size in a
      multicellular organism, which will give a novel insight into the mechanisms of
      body size control.

PMID- 17535252
TI  - HSP90 cross-links branched actin filaments induced by N-WASP and the Arp2/3
      complex.
AB  - N-WASP induces filopodial actin cytoskeleton through activation of the Arp2/3
      complex. Here, we show that heat shock protein 90 (HSP90) regulates the structure
      of actin filaments induced by N-WASP and the Arp2/3 complex. HSP90 binds to N
      WASP and to F-actin and bundles actin filaments. Bundling activity of HSP90 does
      not affect actin filament nucleation induced by N-WASP and the Arp2/3 complex.
      HSP90 is co-localized with N-WASP at branching points of actin filaments produced
      by the Arp2/3 complex and thereby bundles branched filaments; this bundled actin
      structure is inhibited by blocking direct binding between HSP90 and N-WASP.
      Furthermore, HSP90 converts branched actin filaments on N-WASP-coated beads to
      filopodia-like star-shaped bundles. These findings indicate that HSP90 promotes
      the formation of N-WASP/Arp2/3 complex-induced unbranched filopodial actin
      structures.

PMID- 17535253
TI  - Rho-kinase dependent organization of stress fibers and focal adhesions in
      cultured fibroblasts.
AB  - The activation of Rho-kinase is known to modulate the organization of the actin
      based cytoskeletal systems, including the formation of stress fibers and focal
      adhesions. Rho-kinase likely plays a more crucial and complex role in the
      organization of actin-based cytoskeletal systems than in that of myosin light
      chain kinase (MLCK). In order to understand the role of Rho-kinase in the
      organization of stress fibers and focal adhesions, we treated cultured
      fibroblasts with a Rho-kinase inhibitor and analyzed the stress fiber and focal
      adhesion organization under conventional fluorescence microscopy and replica
      electron microscopy. Some of the cells were transfected with GFP-labeled
      paxillin, actin or alpha-actinin, and the effects of the inhibitor were monitored
      in the living cells. The Rho-kinase inhibitor caused disassembly of the stress
      fibers and focal adhesions in the central portion of the cell within 1 h.
      However, the stress fibers and focal adhesions located in the cell periphery were
      not as severely affected by the Rho-kinase inhibitor. The time-lapse video
      recording revealed that when these cells were washed with a fresh medium in order
      to remove the Rho-kinase inhibitor, the stress fibers and focal adhesions located
      in the center of the cell gradually reorganized and, within 1.5-2 h, the cells
      completely recovered. This observation strongly suggests that the activation of
      Rho-kinase plays an important role in the organization of the central stress
      fibers and focal adhesions.

PMID- 17535254
TI  - The role of N-terminal domain of translational release factor eRF3 for the
      control of functionality and stability in S. cerevisiae.
AB  - Translation termination in eukaryotes is mediated by two eukaryotic release
      factors, eRF1 and eRF3. eRF1 recognizes all three stop codons and induces
      polypeptide release, while eRF3 binds to eRF1 and participates in translation
      termination though the regulatory role of eRF3 is still unknown. Importantly,
      eRF3 interacts with various proteins of distinct biological functions. Here, we
      investigated the effect of these binding factors on functionality and stability
      of eRF3 using a temperature-sensitive mutant eRF3ts, which is susceptible to
      factor binding to change the growth phenotype or cellular protein level. Of
      factors tested, Itt1 over-expression and Sla1 knockout severely impaired
      viability of eRF3ts cell and its protein abundance in permissive and
      semipermissive conditions. Sla1 over-expression reversed the phenotype. It is
      reported that Itt1 and Sla1 bind to the N-terminal extension domain (NED) of
      eRF3, unlike the other no-effect factors that bind to the C-terminal domain
      (CTD). Although NED itself is dispensable, NED-less eRF3ts altered in the
      stability and functionality. Moreover, Itt1-induced eRF3ts lethality was
      significantly restored by pep4, prb1 and prc1 knockouts that are defective in
      vacuolar proteolysis. These findings suggest that NED functions to switch the
      functional mode of eRF3 depending on the nature of binding factors.

PMID- 17535255
TI  - Involvement of integrin-induced activation of protein kinase C in the formation
      of adherens junctions.
AB  - In epithelial cells, tight junctions (TJs) and adherens junctions (AJs) form
      junctional complexes. At AJs, cadherins and nectins are the major cell-cell
      adhesion molecules. Nectins first form cell-cell adhesions and then recruit
      cadherins to the nectin-based cell-cell adhesion sites to form AJs in
      coordination with the activation of integrin alpha(v)beta(3), followed by the
      formation of TJs. We previously demonstrated that when MDCK cells precultured at
      a low Ca(2+) concentration were treated with the protein kinase C (PKC) activator
      12-O-tetradecanoyl-phorbol-13-acetate (TPA), incomplete AJs and a TJ-like
      structure were achieved. However, it remains unknown how PKC is activated and how
      it regulates the formation of cell-cell junctions. When MDCK cells precultured at
      a low Ca(2+) concentration were treated with TPA, incomplete AJs were formed
      without the activation of integrin alpha(v)beta(3). Treatment of cells with TPA
      also enhanced the phosphorylation of FAK, which transmits the outside-in signal
      of integrin and plays a role in the nectin-induced formation of AJs. In addition,
      inhibition of PKC suppressed the formation of AJs. These results indicate that
      the activation of PKC functions downstream of integrin alpha(v)beta(3) and
      upstream of FAK, and is important for the nectin-induced formation of AJs.

PMID- 17535256
TI  - Actin filaments-stabilizing and -bundling activities of cofilin-phosphatase
      Slingshot-1.
AB  - Slingshot-1 (SSH1) is known to regulate actin filament dynamics by
      dephosphorylating and activating cofilin, an actin-depolymerizing factor. SSH1
      binds to filamentous (F-) actin through its multiple F-actin-binding sites and
      its cofilin-phosphatase activity is enhanced by binding to F-actin. In this
      study, we demonstrate that SSH1 has F-actin-stabilizing and -bundling activities.
      In vitro actin depolymerization assays revealed that SSH1 suppressed spontaneous
      and cofilin-induced actin depolymerization in a dose-dependent manner. SSH1
      inhibited F-actin binding and severing activities of cofilin. Low-speed
      centrifugation assays combined with fluorescence and electron microscopic
      analysis revealed that SSH1 has F-actin-bundling activity, independently of its
      cofilin-phosphatase activity. Deletion of N- or C-terminal regions of SSH1
      significantly reduced its F-actin-stabilizing and -bundling activities,
      indicating that both regions are critical for these functions. As SSH1 does not
      form a homodimer, it probably bundles F-actin through its multiple F-actin
      binding sites. Knockdown of SSH1 expression by RNA interference significantly
      suppressed stress fiber formation in C2C12 myoblast cells, indicating a role for
      SSH1 in stress fiber formation or stabilization in cells. SSH1 thus has the
      potential to regulate actin filament dynamics and organization in cells via F
      actin-stabilizing and -bundling activities, in addition to its ability to
      dephosphorylate cofilin.

PMID- 17535257
TI  - Two-step, extensive alterations in the transcriptome from G0 arrest to cell
      division in Schizosaccharomyces pombe.
AB  - Body cells in multicellular organisms are in the G0 state, in which cells are
      arrested and terminally differentiated. To understand how the G0 state is
      maintained, the genes that are specifically expressed or repressed in G0 must be
      identified, as they control G0. In the fission yeast Schizosaccharomyces pombe,
      haploid cells are completely arrested under nitrogen source starvation with high
      viability. We examined the global transcriptome of G0 cells and cells on the
      course to resume vegetative growth. Approximately 20% of the transcripts of
      approximately 5000 genes increased or decreased more than fourfold in the two
      step transitions that occur prior to replication. Of the top 30 abundant
      transcripts in G0, 23 were replaced by ribosome- and translation-related
      transcripts in the dividing vegetative state. Eight identified clusters with
      distinct alteration patterns of approximately 2700 transcripts were annotated by
      Gene Ontology. Disruption of 53 genes indicated that nine of them were necessary
      to support the proper G0 state. These nine genes included two C2H2 zinc finger
      transcription factors, a cyclin-like protein implicated in phosphorylation of RNA
      polymerase II, two putative autophagy regulators, a G-protein activating factor,
      and two CBS domain proteins, possibly involved in AMP-activated kinase.

PMID- 17535258
TI  - Small-scale in vivo imaging of soft tissues by radioscopy using single X-ray
      photon counting.
AB  - A method has been developed for routine laboratory visualisation of small-scale
      soft tissue by means of transmission X-ray radioscopy and tomography. Using
      termites as models, imaging quality with a spatial resolution of about 3 mum was
      achieved and 3D tomographic reconstruction was demonstrated. A termite worker
      individual was visualized before and after its metamorphosis towards the soldier
      caste. The developed methodology represents a non-invasive and real-time way of
      acquiring 3D anatomic data with a high contrast so that it is a promising
      candidate to become a tool for routine investigations in life sciences.

PMID- 17535259
TI  - Fibre-optic nonlinear optical microscopy and endoscopy.
AB  - Nonlinear optical microscopy has been an indispensable laboratory tool of high
      resolution imaging in thick tissue and live animals. Rapid developments of fibre
      optic components in terms of growing functionality and decreasing size provide
      enormous opportunities for innovations in nonlinear optical microscopy. Fibre
      based nonlinear optical endoscopy is the sole instrumentation to permit the
      cellular imaging within hollow tissue tracts or solid organs that are
      inaccessible to a conventional optical microscope. This article reviews the
      current development of fibre-optic nonlinear optical microscopy and endoscopy,
      which includes crucial technologies for miniaturized nonlinear optical microscopy
      and their embodiments of endoscopic systems. A particular attention is given to
      several classes of photonic crystal fibres that have been applied to nonlinear
      optical microscopy due to their unique properties for ultrashort pulse delivery
      and signal collection. Furthermore, fibre-optic nonlinear optical imaging systems
      can be classified into portable microscopes suitable for imaging behaving
      animals, rigid endoscopes that allow for deep tissue imaging with minimally
      invasive manners, and flexible endoscopes enabling imaging of internal organs.
      Fibre-optic nonlinear optical endoscopy is coming of age and a paradigm shift
      leading to optical microscope tools for early cancer detection and minimally
      invasive surgery.

PMID- 17535260
TI  - Atomic force microscope (AFM) combined with the ultramicrotome: a novel device
      for the serial section tomography and AFM/TEM complementary structural analysis
      of biological and polymer samples.
AB  - A new device (NTEGRA Tomo) that is based on the integration of the scanning probe
      microscope (SPM) (NT-MDT NTEGRA SPM) and the Ultramicrotome (Leica UC6NT) is
      presented. This integration enables the direct monitoring of a block face surface
      immediately following each sectioning cycle of ultramicrotome sectioning
      procedure. Consequently, this device can be applied for a serial section
      tomography of the wide range of biological and polymer materials. The automation
      of the sectioning/scanning cycle allows one to acquire up to 10 consecutive
      sectioned layer images per hour. It also permits to build a 3-D nanotomography
      image reconstructed from several tens of layer images within one measurement
      session. The thickness of the layers can be varied from 20 to 2000 nm, and can be
      controlled directly by its interference colour in water. Additionally, the NTEGRA
      Tomo with its nanometer resolution is a valid instrument narrowing and
      highlighting an area of special interest within volume of the sample. For
      embedded biological objects the ultimate resolution of SPM mostly depends on the
      quality of macromolecular preservation of the biomaterial during sample
      preparation procedure. For most polymer materials it is comparable to
      transmission electron microscopy (TEM). The NTEGRA Tomo can routinely collect
      complementary AFM and TEM images. The block face of biological or polymer sample
      is investigated by AFM, whereas the last ultrathin section is analyzed with TEM
      after a staining procedure. Using the combination of both of these
      ultrastructural methods for the analysis of the same particular organelle or
      polymer constituent leads to a breakthrough in AFM/TEM image interpretation.
      Finally, new complementary aspects of the object's ultrastructure can be
      revealed.

PMID- 17535261
TI  - Determination of diffusion controlled reaction rates at a solid/liquid interface
      using scanning electron microscopy.
AB  - A high-resolution method has been developed for the determination of localized
      values of interfacial reaction rate and mass transfer coefficient in aqueous
      solution. Scanning electron microscopy has been successfully applied to this
      problem through the measurement of electroplated film thickness formed under
      limiting current conditions. The method involves the calculation of local values
      of reaction rate via Faraday's laws and subsequent conversion of the data to
      absolute values of mass transfer coefficient. The technique has been verified in
      an undisturbed, turbulent flow regime (rotating cylinder electrode) through the
      use of Sherwood group dimensionless analysis. The resulting relationship shows
      comparable accuracy relative to electrochemical measurements. Favourable
      comparison has also been made with the generally accepted rotating cylinder
      correlation of Eisenberg, Tobias and Wilke. Differential rates of mass transfer
      to a single surface under conditions of disturbed flow have also been examined at
      a high spatial resolution using the stepped rotating cylinder electrode geometry.
      In this case, reaction rates have been measured as a function of circumferential
      distance within a recirculation zone situated immediately downstream of a
      backward-facing step.

PMID- 17535262
TI  - Real-time image quality assessment with mixed Lagrange time delay estimation
      autoregressive (MLTDEAR) model.
AB  - A proposal to assess the quality of scanning electron microscope images using
      mixed Lagrange time delay estimation technique is presented. With optimal
      scanning electron microscope scan rate information, online images can be
      quantified and improved. The online quality assessment technique is embedded onto
      a scanning electron microscope frame grabber card for real-time image processing.
      Different images are captured using scanning electron microscope and a database
      is built to optimally choose filter parameters. An optimum choice of filter
      parameters is obtained. With the optimum choice of scan rate, noise can be
      removed from real-time scanning electron microscope images without causing any
      sample contamination or increasing scanning time.

PMID- 17535263
TI  - Semi-automated imaging system to quantitate estrogen and progesterone receptor
      immunoreactivity in human breast cancer.
AB  - A semi-automated imaging system is described to quantitate estrogen and
      progesterone receptor immunoreactivity in human breast cancer. The system works
      for any conventional method of image acquisition using microscopic slides that
      have been processed for immunohistochemical analysis of the estrogen receptor and
      progesterone receptor. Estrogen receptor and progesterone receptor
      immunohistochemical staining produce colorimetric differences in nuclear staining
      that conventionally have been interpreted manually by pathologists and expressed
      as percentage of positive tumoral nuclei. The estrogen receptor and progesterone
      receptor status of human breast cancer represent important prognostic and
      predictive markers of human breast cancer that dictate therapeutic decisions but
      their subjective interpretation result in interobserver, intraobserver and
      fatigue variability. Subjective measurements are traditionally limited to a
      determination of percentage of tumoral nuclei that show positive
      immunoreactivity. To address these limitations, imaging algorithms utilizing both
      colorimetric (RGB) as well as intensity (gray scale) determinations were used to
      analyze pixels of the acquired image. Image acquisition utilized either scanner
      or microscope with attached digital or analogue camera capable of producing
      images with a resolution of 20 pixels /10 mu. Areas of each image were screened
      and the area of interest richest in tumour cells manually selected for image
      processing. Images were processed initially by JPG conversion of SVS scanned
      virtual slides or direct JPG photomicrograph capture. Following image
      acquisition, images were screened for quality, enhanced and processed. The
      algorithm-based values for estrogen receptor and progesterone receptor percentage
      nuclear positivity both strongly correlated with the subjective measurements
      (intraclass correlation: 0.77; 95% confidence interval: 0.59, 0.95) yet exhibited
      no interobserver, intraobserver or fatigue variability. In addition the
      algorithms provided measurements of nuclear estrogen receptor and progesterone
      receptor staining intensity (mean, mode and median staining intensity of positive
      staining nuclei), parameters that subjective review could not assess. Other semi
      automated image analysis systems have been used to measure estrogen receptor and
      progesterone receptor immunoreactivity but these either have required proprietary
      hardware or have been based on luminosity differences alone. By contrast our
      algorithms were independent of proprietary hardware and were based on not just
      luminosity and colour but also many other imaging features including epithelial
      pattern recognition and nuclear morphology. These features provide a more
      accurate, versatile and robust imaging analysis platform that can be fully
      automated in the near future. Because of all these properties, our semi-automated
      imaging system 'adds value' as a means of measuring these important nuclear
      biomarkers of human breast cancer.

PMID- 17535264
TI  - Routine fluorescence microscopy of single untethered protein molecules confined
      to a planar zone.
AB  - To bypass limitations of ensemble averaging biochemical analysis, microscopy
      based detection and tracking are needed for single protein molecules that are
      diffusing in aqueous solution. Confining the molecules to a planar zone
      dramatically assists tracking. Procedures of microscopy should be routine enough
      so that effort is focused on the biochemistry. Fluorescence microscopy and
      partial planar confinement of single, untethered, aqueous protein molecules have
      been achieved here by use of a routine procedure. With this procedure, multiple
      thermally diffusing Alexa 488-stained bovine serum albumin molecules were
      observed during partial confinement to a thin aqueous zone next to a cover slip.
      The procedure produces confinement by partial re-swelling of a previously dried
      agarose gel on the microscope slide. Confinement was confirmed through analysis
      that revealed thermal motion lower in the third dimension than it was in the
      plane of observation.

PMID- 17535265
TI  - A technique for improved focused ion beam milling of cryo-prepared life science
      specimens.
AB  - The combination of focused ion beam and scanning electron microscopy with a cryo
      preparation/transfer system allows specimens to be milled at low temperatures.
      However, for biological specimens in particular, the quality of results is
      strongly dependent on correct preparation of the specimen surface. We demonstrate
      a method for deposition of a protective, planarizing surface layer onto a cryo
      sample, enabling high-quality cross-sectioning using the ion beam and
      investigation of structures at the nanoscale.

PMID- 17535266
TI  - Retrieving true images through fine grid steps for enhancing the resolution
      beyond the classical limits: theory and simulations.
AB  - We developed the theory of, and tested by extended simulations, a novel method
      for retrieving true images in a grid step much finer than both the acquisition
      and the optical microscope limits. We believe that the method is promising in
      view of avoiding the limitations on the resolution improvement in direct imaging
      mode systems. Two basic concepts are involved: (i) random (up to 3D) relative
      displacements of objects with respect to the receiving matrix and (ii) the use of
      a reference object firmly fixed to small signal objects for avoiding the
      displacement measurements. The retrieved images are created by rearranging a set
      of true images acquired with a lower resolution equal to the matrix pixel size.
      We demonstrate the good quality of the retrieved images and the possibility to
      visualize and detect small (convolved) objects not observed into the captured
      images. The method provides good opportunities for effective applications of
      different inverse algorithms for improving the resolution requiring, as a rule,
      more precisely sampled images, but at arbitrary relations between the pixel size
      and the optical diffraction limit. We further demonstrated the application of
      some deconvolution procedures for extracting highly resolved images in the object
      and image planes in the presence of noise. The possibility to resolve small
      objects beyond the two classical limits is shown by means of simulations. The
      estimates for the method's limiting resolution, combined with proper
      deconvolution processing, show that resolution in the lower nano-dimension scale
      (below 10 nm) could be achieved. The requirements to the implementation of the
      novel method are commented as well.

PMID- 17535267
TI  - Allelic association and recombination hotspots in the mucin gene (MUC) complex on
      chromosome 11p15.5.
AB  - A family of four highly polymorphic genes encoding secreted gel forming mucins is
      located in the middle of a recombination rich region of the short arm of
      chromosome 11 (11p15.5; tel MUC6-MUC2-MUC5AC-MUC5B cen; approx. 400 kb). These
      genes are of interest as risk factors for inflammatory diseases of the epithelia,
      and we have for example reported association of a VNTR polymorphism of the major
      mucin domain of MUC2 with asthma, despite the fact that MUC2 is not a major
      respiratory mucin. To understand the significance of this and other mucin gene
      associations it is important to describe the patterns of linkage disequilibrium
      (LD) across this chromosomal region, which is still incomplete on HapMap and the
      UCSC Golden Path sequence. Our previous studies on the 40 core CEPH families
      provided direct evidence for several recombination events within the immediate
      region of the gene complex. This study examines these recombination events in
      more detail, and also the patterns of LD across the gene complex. We refine the
      location of the breakpoints, and the combined data suggest two probable
      recombination hotspots. Three breakpoints are located between MUC6 and MUC2:
      there is no association between MUC6 and MUC2, and the data collected here,
      combined with that publicly available, maps a hotspot to a region of 4 kb. The
      other recombinants map between MUC2 and intron 8 of MUC5B. Relatively strong LD
      is detected between MUC2 and MUC5AC, and although 10/70 of the chromosomes tested
      shared a common haplotype, which extends from MUC2 to MUC5B, statistically
      significant association was not detected between MUC2 and the markers tested in
      MUC5B. We discuss the possibility that the previously reported association
      between MUC2 and asthma is most likely attributable to association with
      functional variation in MUC5AC, which encodes one of the two major mucins
      expressed in both healthy and diseased airways.

PMID- 17535268
TI  - Fatal malonyl CoA decarboxylase deficiency due to maternal uniparental isodisomy
      of the telomeric end of chromosome 16.
AB  - Malonic aciduria is a rare autosomal recessive disorder caused by deficiency of
      malonyl-CoA decarboxylase, encoded by the MLYCD gene. We report on a patient with
      clinical presentation in the neonatal period. Metabolic investigations led to a
      diagnosis of malonyl-CoA decarboxylase deficiency, confirmed by decreased
      activity in cultured fibroblasts. High doses of carnitine and a diet low in
      lipids led to a reduction in malonic acid excretion, and to an improvement in his
      clinical conditions, but at the age of 4 months he died suddenly and
      unexpectedly. No autopsy was performed. Molecular analysis of the MLYCD gene
      performed on the proband's RNA and genomic DNA identified a previously
      undescribed mutation (c.772-775delACTG) which was homozygous. This mutation was
      present in his mother but not in his father; paternity was confirmed by
      microsatellite analysis. A hypothesis of maternal uniparental disomy (UPD) was
      investigated using fourteen microsatellite markers on chromosome 16, and the
      results confirmed maternal UPD. Maternal isodisomy of the 16q24 region led to
      homozygosity for the MLYCD mutant allele, causing the patient's disease. These
      findings are relevant for genetic counselling of couples with a previously
      affected child, since the recurrence risk in future pregnancies is dramatically
      reduced by the finding of UPD. In addition, since the patient had none of the
      clinical manifestations previously associated with maternal UPD 16, this case
      provides no support for the existence of maternally imprinted genes on chromosome
      16 with a major effect on phenotype.

PMID- 17535269
TI  - Association of microsatellite polymorphisms of the human 14q13.2 region with type
      2 diabetes mellitus in Latvian and Finnish populations.
AB  - A polymorphic microsatellite in intron 6 of the human proteasome core particle
      PSMA6 gene (HSMS006), and four other microsatellites localized upstream on human
      chromosome 14q13.2 (HSMS801, HSMS702, HSMS701, HSMS602), were genotyped in 104
      type 2 diabetic patients and 129 age-matched control subjects from Latvia and
      replicated in 91 type 2 diabetic patients and 88 age-matched healthy control
      subjects from the Botnia Study in Finland. In type 2 diabetic patients from both
      populations the HSMS006 (TG)22 allele was two times more frequent compared to the
      control group. In the Latvian population the (CAA)8 allele of the HSMS602 marker
      was less frequent in the diabetic group, as was the (AC)24 allele of
      microsatellite HSMS801. Allele frequencies of the HSMS701 and 702 repeats were
      similar in healthy controls and type 2 diabetic patients. In conclusion, our data
      suggest that variants in the PSMA6 gene on chromosome 14q13.2 are associated with
      type 2 diabetes.

PMID- 17535271
TI  - Founder effect of the 669insA mutation in BSCL2 gene causing Berardinelli-Seip
      congenital lipodystrophy in a cluster from Brazil.
AB  - Congenital generalized lipodystrophy (CGL) or Berardinelli-Seip Syndrome (BSCL)
      is a rare autosomal recessive disease characterized by a nearly-complete absence
      of adipose tissue from birth and severe metabolic alterations. The 669insA
      mutation in exon 4 of the BSCL2 gene was identified as the major genetic
      alteration leading to BSCL in a group of 22 patients from the northeastern
      Brazilian state of Rio Grande do Norte. Aiming to investigate the causes of the
      high frequency of BSCL in this region, a molecular genetic study was conducted
      using eight microsatelite markers located in chromosome 11. Additional
      investigations concerning the proportion of expected homozygous and heterozygous
      individuals, genetic diversity, fixation index and coefficient of endogamy were
      undertaken, and indicated significant differences by comparing the allelic and
      haplotypic frequencies observed for the BSCL affected families and the control
      group. It was concluded that a founder effect, genetic drift and consanguineous
      marriages have significantly affected the structure of this population, resulting
      in the highest frequency of BSCL in Brazil.

PMID- 17535270
TI  - Variation in 5' promoter region of the APOE gene contributes to predicting
      ischemic heart disease (IHD) in the population at large: the Copenhagen City
      Heart Study.
AB  - The objective of this study was to evaluate whether an increased hazard of
      developing ischemic heart disease (IHD) is associated with any of the three
      genotypes A560T832/A560T832, A560T832/A560G832 and A560T832/T560T832, defined by
      variations in two non-coding SNPs in the 5' promoter region of the apolipoprotein
      E (APOE) gene. These genotypes were selected because they distinguished between
      high and low levels of HDL-C, TG and/or T-C in our earlier study of multiple
      samples defined by gender and population. We found a significant increase
      (p<0.05) in the hazard of IHD in females with the A560T832/T560T832 genotype that
      remained significant after fitting the effects of dyslipidemia, other established
      risk factors, and the structural isoform variations of the ApoE molecule. We
      discuss why this statistically significant genetic predictor may not be an
      appropriate screening test for IHD in the Danish population at large.

PMID- 17535272
TI  - Prevalence and clinical characteristics of immune thrombocytopenic purpura in a
      cohort of monoclonal gammopathy of uncertain significance.
AB  - Monoclonal gammopathy of uncertain significance (MGUS) may become symptomatic for
      autoimmune manifestations. We report on the prevalence and clinical course of
      immune thrombocytopenic purpura (ITP) observed in a consecutive series of 228
      MGUS patients. At MGUS diagnosis, ITP was determined in 6/228 cases, accounting
      for a prevalence of 2630/100 000 [95% confidence interval (CI): 1210-5620]. One
      incidental ITP case occurred after 21 months of follow-up. After a follow-up of
      681.3 patient-years, the crude incidence of ITP in MGUS was 146.8 per 100 000
      patient-year (95% CI: 3.7-817.8). Overall, these observations point to an
      association between MGUS and ITP.

PMID- 17535273
TI  - A more selective approach to prostate biopsy could be a safe and effective form
      of prostate cancer 'prevention'.

PMID- 17535274
TI  - Prolonged follow-up after paediatric pyeloplasty: are repeat scans necessary?
AB  - OBJECTIVE: To establish the value of repeat renal scans to assess the relative
      renal function after successful paediatric pyeloplasty. PATIENTS AND METHODS:
      Renal scans were assessed from 138 patients after successful pyeloplasty; the
      relative renal function before and immediately after pyeloplasty were compared,
      as was split renal function at 3.5 and 5.5 years after surgery. RESULTS: With a
      few exceptions the relative renal function before and after pyeloplasty was
      stable. Repeat renal scans 3.5 and 5.5 years after surgery also showed stable
      split renal function, even if the renal function was already diminished.
      CONCLUSIONS: Repeat renal scans are not necessary after successful pyeloplasty in
      children, as most operated renal units showed stable renal function for 5-7
      years. Further studies are needed to investigate whether renal function changes
      further after puberty.

PMID- 17535275
TI  - Robotic Anderson-Hynes pyeloplasty: 5-year experience of one centre.
AB  - OBJECTIVE: To present our 5-year experience with robotically assisted
      laparoscopic pyeloplasty (RALP), as LP has been shown to have similar success
      rates as open surgery, but standard LP requires high operative skills and a
      correspondingly long period of training, limiting its widespread availability,
      and RALP is easier and quicker to learn due to facilitated intracorporeal
      suturing. PATIENTS AND METHODS: In all, 92 patients had transperitoneal RALP for
      pelvi-ureteric junction obstruction (PUJO) using the daVinci system (Intuitive
      Surgical, Sunnyvale, CA, USA). A transperitoneal dismembered Anderson-Hynes
      procedure was used in all cases. Three robotic ports and one assistant port were
      used in all cases while a JJ stent was left indwelling for 6 weeks. Both primary
      PUJO (including horseshoe kidneys in 80 cases) and secondary (in 12 cases) were
      considered eligible. The follow-up included ultrasonography, excretory urography
      and renal scintigraphy. RESULTS: The mean follow-up was 39.1 months; PUJO was
      successfully resolved in 89 patients (96.7%) while three required additional
      procedures. Haemorrhage into the collecting system and urine extravasation
      occurring early after surgery were the causes of failure. The mean (range)
      operative duration, including the set-up of the robot, was 108.34 (72-215) min;
      the mean duration of docking and surgery significantly decreased with experience
      (P < 0.001). The mean hospital stay was 4.57 days. Split renal function improved
      from 37.6% to 41.9%. No cases of secondary PUJO were recorded during extended
      follow-up. CONCLUSIONS: RALP using the daVinci system is safe and effective,
      achieving similar long-term success rates to open surgery. The three-dimensional
      versatility of the robot enables the surgeon to recapitulate the open procedure.
      The results were durable with no cases of late complications, corroborating the
      accuracy of robot-assisted intracorporeal suturing and the subsequent quality of
      the pelvi-ureteric anastomosis. Moreover, the robotic approach was easy and quick
      to learn for both the surgical and the technical staff. Therefore, RALP is our
      preferred technique to treat PUJO.

PMID- 17535276
TI  - Weekly high-dose calcitriol and docetaxel in patients with metastatic hormone
      refractory prostate cancer previously exposed to docetaxel.
AB  - OBJECTIVE: To evaluate the activity and tolerability of weekly high-dose
      calcitriol and docetaxel in patients with metastatic hormone-refractory prostate
      cancer (HRPC) previously exposed to docetaxel, as patients who progress after
      docetaxel treatment might be considered for second-line chemotherapy, but with no
      standard salvage therapy available we hypothesised that high-dose calcitriol
      might restore sensitivity to chemotherapy. PATIENTS AND METHODS: The study
      comprised 26 patients who had progressed after first-line treatment with
      docetaxel-based chemotherapy had failed. Treatment cycles consisted of calcitriol
      (32 microg orally as 0.5 microg tablets) on day 1 and docetaxel (30 mg/m(2)
      intravenous) on day 2, administered for six consecutive weeks followed by a 2
      week rest interval for a maximum of 24 cycles. RESULTS: There was a response in
      prostate-specific antigen (PSA) level in eight patients (31%); seven (27%) had a
      stable PSA level for >/= 12 weeks. The median time to PSA progression was 4.2
      months and the median survival was 9.3 months. The regimen was generally well
      tolerated; there was grade 2 hypercalcaemia, probably related to calcitriol, in
      one patient after six treatment cycles. CONCLUSION: Weekly high-dose calcitriol
      and docetaxel seems to be an effective and well-tolerated treatment option for
      patients with metastatic HRPC previously exposed to docetaxel-based chemotherapy.

PMID- 17535277
TI  - Does a constriction ring alter ejaculation latency?
AB  - OBJECTIVE: To assess the efficacy of a 'constriction ring' as an option for
      treating premature ejaculation (PE). PATIENTS AND METHODS: Between September 2003
      and October 2006, 42 men with an intravaginal ejaculation latency time (IELT) of
      <1 min were evaluated. Over a 4-week period, a constriction ring was used during
      intercourse. RESULTS: The median (range) IELT was 42 (33-54) s before treatment
      and 46 (31-55) s after 4 weeks of using the ring; there was no statistically
      significant difference in the IELT before and after treatment (P = 0.1), and no
      major complications. CONCLUSION: The 'constriction ring' is not an effective
      treatment for PE.

PMID- 17535278
TI  - A randomized controlled trial of topical glyceryl trinitrate before transrectal
      ultrasonography-guided biopsy of the prostate.
AB  - OBJECTIVES: To evaluate the use of topical glyceryl trinitrate (GTN) ointment as
      an adjunct to periprostatic nerve block in reducing pain associated with
      transrectal ultrasonography (TRUS)-guided prostatic biopsy. PATIENTS AND METHODS:
      In all, 148 consecutive patients (mean age 67.0 years) having their first TRUS
      guided biopsy were randomized to receive either 0.2% GTN ointment or placebo 10
      min before biopsy. All patients had a biopsy preceded by an injection with 10 mL
      of 1% lidocaine local anaesthesia. A 10-point visual analogue score was used to
      record 'Overall discomfort due to the presence of the probe', the biopsy itself
      and pain after the procedure. RESULTS: There was no significant difference in
      age, PSA level and prostate volume between the groups. There was a significantly
      lower mean pain score due to probe insertion in the GTN than placebo group (1.94
      vs 3.24, P < 0.01); pain perception was lower for the whole procedure in the GTN
      group, and was most pronounced in men aged <60 years (2.13 vs 4.61, P < 0.005).
      CONCLUSIONS: Topical GTN ointment is safe and effective in reducing the
      discomfort associated with TRUS-guided biopsy of the prostate, in particular the
      insertion of the ultrasound probe. It might be of maximum benefit in the younger
      patient and those having a repeat biopsy who previously failed to tolerate the
      procedure well.

PMID- 17535279
TI  - Is the circumferential resection margin a predictor of local recurrence after
      preoperative radiotherapy and optimal surgery for rectal carcinoma?
AB  - OBJECTIVE: Circumferential resection margin (CRM) involvement has been correlated
      with a high risk of developing local recurrence. The aim of this study was to
      examine the prognostic significance of the CRM involvement after curative
      resection of rectal cancer in patients treated with preoperative radiotherapy and
      postoperative chemotherapy where indicated. METHOD: All patients with rectal
      cancer treated in a regional central unit from 1996 to 2004 were identified. A
      surgical resection was performed on 257 patients, and in 229 of these this was
      assessed as potentially curative. The CRM was examined in all patients. A CRM of
      < or = 1 mm was considered positive. RESULTS: A positive margin was seen in 19
      (8%) patients. At a median follow up of 40 months, only four (1.7%) patients had
      developed local recurrence, one of whom had a positive CRM. In the four patients
      the tumour was 5 cm or less from the anal verge. There were no significant
      differences regarding local recurrence and survival between CRM positive and
      negative tumours. CONCLUSION: Rectal cancer managed by combined radiochemotherapy
      and surgery resulted in a low positive CRM rate and a low local recurrence rate.
      An involved CRM was not a predictor of local recurrence.

PMID- 17535280
TI  - Granulomatous variant of chronic pigmented purpuric dermatoses: report of four
      new cases and an association with hyperlipidaemia.
AB  - Four patients presenting with chronic pigmented purpuric dermatosis (CPPD) on the
      limbs were found to have granulomatous inflammation superimposed on the
      pathological changes of CPPD. Three of the four patients had hyperlipidaemia.
      Therefore, the granulomatous reaction observed could be associated with
      hyperlipidaemia. Whether it occurs only in Asian people or not needs further
      observation.

PMID- 17535281
TI  - Local expression of TAP-1 and MHC-I molecules and their relationship in condyloma
      acuminatum.
AB  - BACKGROUND: Condyloma acuminatum (CA), caused by human papillomavirus (HPV), is
      characterized by a variable clinical course that can include significant
      morbidity, frequent disease recurrence and occasional oncogenicity. Effective
      CD8+ T-cell-mediated clearance of HPV-infected cells may be defective in patients
      with CA, leading to recurrent disease and failure to suppress latent HPV
      reactivation. The pathogenesis responsible for CA and the persistence of latent
      HPV infection remain unknown. OBJECTIVE: To determine whether expression of
      transporters associated with antigen processing 1 (TAP-1) and the major
      histocompatibility complex class I (MHC-I) is involved in HPV immune escape.
      METHODS: In this present study, we compared 31 CA lesions with 30 normal prepuces
      by immunohistochemistry and reverse transcription PCR for their expressions of
      TAP-1 and MHC-I. RESULTS: Expressions of TAP-1 and MHC-I were significantly
      reduced in CA tissue biopsies compared with normal prepuces. There was a
      statistically significant positive correlation between expressions of TAP-1 and
      MHC-I in CA lesions. Furthermore, we found that TAP-1 mRNA was significantly
      reduced in CA lesions compared with those in normal prepuces. CONCLUSION: These
      results suggest that HPV may evade immune recognition by downregulating MHC-I
      cell surface expression via decreased TAP-1 levels.

PMID- 17535282
TI  - The effect of vitamin E on acute skin reaction caused by radiotherapy.
AB  - Ionizing radiation affects healthy organs and tissues as well as diseased tissues
      during radiation therapy. Skin reactions varying from acute erythema to necrosis
      can be seen. It has been found that vitamin E can prevent mutagenic and/or
      carcinogenic effects of ionizing radiation in both animals and cell cultures.
      This study investigated the preventative effect of antioxidant vitamin E on
      irradiation-induced acute skin reactions. No protective effect of vitamin E was
      demonstrated. It is possible that the vehicle induced free radical exposure in
      the irradiated skin.

PMID- 17535283
TI  - A painful scrotal eruption.

PMID- 17535284
TI  - Subjective intensity of pain during ultrasonic supragingival calculus removal.
AB  - OBJECTIVE: To assess subjective intensities of pain during supragingival calculus
      removal employing ultrasonic scaler tips of two different shapes. MATERIAL AND
      METHODS: Twenty patients were treated using a piezoelectric ultrasonic device
      (Sirosonic L) and two different scaler tips representing a conventional
      (Instrument No. 3) and a slim-line style (Perio Pro Line Instrument SI-11) in a
      split-mouth design. Pain was recorded during calculus removal at intervals of 0.5
      s employing an inter-modal intensity comparison. Additionally, a visual analogue
      scale was used for evaluation directly after the treatment procedure. Treatment
      time was recorded to assess the efficiency of calculus removal. RESULTS: Pain
      assessment during treatment showed that the slim-line scaler tip (median pain
      score: 1.4 [U], maximum: 3.5 [U], minimum: 0 [U]) caused less pain than the
      conventional device (median pain score: 7.8 [U], maximum: 14.7 [U], minimum: 0
      [U]) (p<0.05). These results could be confirmed by the visual analogue scale.
      Treatment with the slim-line tip took significantly longer than treatment with
      the conventional tip (p<0.05). CONCLUSIONS: Using slim-line-styled ultrasonic
      scaler tips for supragingival calculus removal, painful sensations can be reduced
      compared with conventional ultrasonic devices. Thus, it might be possible to
      increase the patient's compliance during dental treatment with oscillating
      instruments.

PMID- 17535285
TI  - The plaque and gingivitis reducing effect of a chlorhexidine and aluminium
      lactate containing dentifrice (Lacalut aktiv) over a period of 6 months.
AB  - AIM: The aim of the study was to determine the plaque and gingivitis reducing
      effect of a dentifrice containing chlorhexidine and aluminium lactate compared
      with a control toothpaste during the course of 6 months. MATERIAL AND METHODS:
      This randomized, double-blind study looked prospectively at participants over a 6
      month period. Plaque, gingivitis, calculus formation and tooth staining were
      assessed in 59 participants, who were divided into parallel groups. The
      participants used either a chlorhexidine and aluminium lactate-containing
      toothpaste (test group) or a minus active control toothpaste (control group).
      Parameters were assessed at baseline and again after 1, 3 and 6 months. RESULTS:
      After 6 months of product use, both groups had less gingivitis compared with the
      baseline evaluation (p<0.001). At this time point, the test group showed a
      statistically significant lower gingival index values compared with the control
      group (p=0.001). No statistically significant differences between either the
      groups or time points were detected with regard to plaque index and the
      development of calculus and staining. CONCLUSION: Although there was a
      statistically significant difference at 6 months between test and control groups,
      this difference was too small to be considered clinically meaningful.

PMID- 17535286
TI  - Submerged healing following surgical treatment of peri-implantitis: a case
      series.
AB  - OBJECTIVES: The aim was to study a regenerative surgical treatment modality for
      peri-implantitis employing submerged healing. MATERIAL AND METHODS: Twelve
      patients, having a minimum of one osseointegrated implant with peri-implantitis,
      with a progressive loss of >or=3 threads (1.8 mm) following the first year of
      healing were involved in the study. After surgical exposure of the defect,
      granulomatous tissue was removed and the implant surface was treated using 3%
      hydrogen peroxide. The bone defects were filled with a bone substitute
      (Algipore), a resorbable membrane (Osseoquest) was placed over the grafted defect
      and a cover screw was connected to the fixture. The implant was then covered by
      flaps and submerged healing was allowed for 6 months. After 6 months the abutment
      was re-connected to the supra-structure. RESULTS: A 1-year follow-up demonstrated
      clinical and radiographic improvements. Probing depth was reduced by 4.2 mm and a
      mean defect fill of 2.3 mm was obtained. CONCLUSION: Treatment of peri-implant
      defects using a bone graft substitute combined with a resorbable membrane and
      submerged healing results in defect fill and clinical healthier situations.

PMID- 17535287
TI  - Effect of an essential oil-containing antimicrobial mouthrinse on specific plaque
      bacteria in vivo.
AB  - AIM: This study was conducted to investigate the effect of rinsing with an
      essential oil-containing mouthrinse on levels of specific supra and subgingival
      bacteria in subjects with gingivitis. MATERIAL AND METHODS: Fifteen subjects
      meeting entry criteria completed this randomized, controlled, double-blind,
      crossover study. Subjects were required to have >or=1000 target organisms per
      millilitre in pooled samples from two subgingival sites. Following sampling of
      supra and subgingival plaque, subjects began twice-daily rinsing for 14 days with
      either an essential oil-containing mouthrinse (Cool Mint Listerine Antiseptic) or
      a negative control. Supra and subgingival plaque was again sampled on day 15, and
      the procedure repeated after a 1-week washout period with subjects using the
      alternate rinse. RESULTS: Compared with the negative control, the essential oil
      mouthrinse produced significant reductions in supragingival plaque levels of
      Veillonella sp., Capnocytophaga sp., Fusobacterium nucleatum, and total anaerobes
      ranging from 52.3 to 88.5% (p<0.001 except for Veillonella, p=0.002); respective
      reductions in subgingival plaque ranged from 54.1 to 69.1% (p<0.001).
      CONCLUSIONS: Rinsing with the essential oil mouthrinse can have an impact on the
      subgingival plaque flora. This study provides additional evidence indicating that
      reduction in supragingival plaque can reduce levels of subgingival plaque.

PMID- 17535289
TI  - Major increase in Type 1 diabetes: no support for the Accelerator Hypothesis.
AB  - BACKGROUND: The Accelerator Hypothesis postulates that the apparent increase in
      incidence of Type 1 diabetes mellitus (T1DM) is related to an acceleration of
      disease onset by weight-related insulin resistance. Our diabetes clinic has
      experienced a major recent increase in newly diagnosed diabetes. The Accelerator
      Hypothesis predicts that this increase should be associated with younger age and
      increased body mass at diagnosis, with youngest children having the highest body
      mass index (BMI). AIM: To test the Accelerator Hypothesis in the context of the
      major increase in T1DM at our centre. METHODS: Data from all young people
      diagnosed with T1DM between 1992 and 2003 were reviewed. Height and weight
      measurements from initial outpatient review were used to calculate BMI. RESULTS:
      The mean increase in BMI standard deviation score (SDS) is 0.03 per year (P =
      0.01). Age at diagnosis has also increased by a mean of 0.11 years annually (P =
      0.003). There was no association between BMI SDS and age at diagnosis (P = 0.7).
      A significant difference in BMI SDS between age-banded subgroups was evident (P =
      0.04); however, youngest children had the lowest SDS. CONCLUSION: Our results do
      not support increased body mass as an accelerator of diabetes presentation.

PMID- 17535288
TI  - Periodontitis is characterized by elevated PAI-1 activity.
AB  - OBJECTIVES: Periodontitis is a chronic infectious disease and has been associated
      with cardiovascular diseases (CVD). We investigated whether plasma levels of
      markers of a prothrombotic state were elevated in patients with periodontitis in
      comparison with healthy controls. MATERIALS AND METHODS: Untreated patients with
      moderate (n=53) and severe periodontitis (n=38) and healthy controls (n=39) were
      recruited. Levels of von Willebrand factor (vWF), prothrombin fragment 1+2
      (F1+2), plasminogen activator inhibitor-1 (PAI-1) activity and D-dimer were
      measured as markers of a prothrombotic state. RESULTS: The erythrocyte
      sedimentation rate (ESR), plasma C-reactive protein (CRP) and leucocyte counts
      (WBC) were significantly higher in patients with periodontitis. No statistically
      significant difference was found among the three groups for vWF (p=0.264), F1+2
      (p=0.295) and D-dimer (p=0.572). However, PAI-1 was clearly elevated in the
      severe periodontitis group (p=0.001), even after adjusting for potential
      confounding factors (p(adj)=0.004). Moreover, more patients than controls were
      having vWF and PAI-1 levels above the respective population medians. CONCLUSIONS:
      In periodontitis, elevated levels of PAI-1 activity are observed compared with
      healthy controls. This may increase the potential for impaired fibrinolysis, a
      condition that results in a prothrombotic state. We suggest that this state, if
      left untreated, may contribute to an increased risk for CVD.

PMID- 17535290
TI  - A randomized pilot study in Type 1 diabetes complicated by severe hypoglycaemia,
      comparing rigorous hypoglycaemia avoidance with insulin analogue therapy, CSII or
      education alone.
AB  - AIM: To determine potential for amelioration of recurrent severe hypoglycaemia
      without worsening in overall control in individuals with long-standing Type 1
      diabetes (T1DM). METHODS: Twenty-one people with T1DM characterized by altered
      hypoglycaemia awareness and debilitating severe hypoglycaemia were randomized in
      a pilot 24-week prospective study to optimized analogue therapy (ANALOGUE;
      lispro/glargine); continuous subcutaneous insulin infusion therapy (CSII;
      lispro); or re-education with relaxation of blood glucose targets on existing
      conventional insulin regimen (EDUCATION). Glycaemic profiles and duration of
      biochemical hypoglycaemia were measured by continuous subcutaneous glucose
      monitoring and self-monitored blood glucose. RESULTS: Further severe
      hypoglycaemia was prevented in five participants (71%) in each group (P = 0.06).
      Incidence of severe hypoglycaemia was: 0.6 (ANALOGUE), 0.9 (CSII), and 3.7
      (EDUCATION) episodes per patient year. Restoration of hypoglycaemia awareness was
      confirmed by validated questionnaire in three (43%) ANALOGUE, four (57%) CSII and
      five (71%) EDUCATION patients. Glycated haemoglobin (HbA1c) was significantly
      improved in the ANALOGUE group between weeks 0 and 24 (8.6 +/- 1.1 vs. 7.6 +/-
      0.8%; P = 0.04 for change). Non-significant improvement was seen in the CSII
      group (8.5 +/- 1.9 vs. 7.4 +/- 1.0%; P = 0.06). No change in HbA1c was seen in
      the EDUCATION group (8.5 +/- 1.1 vs. 8.3 +/- 1.0%; P = 0.54). There were no
      episodes of diabetic ketoacidosis or any other adverse events in any group.
      CONCLUSIONS: In this pilot randomized trial comparing optimized ANALOGUE, CSII or
      EDUCATION alone in unselected individuals with recurrent severe hypoglycaemia, we
      show potential for restoring hypoglycaemia awareness and preventing further
      severe hypoglycaemia with concomitant improvement in glycaemic control in
      ANALOGUE and CSII groups.

PMID- 17535291
TI  - Evidence for distinct effects of GH and IGF-I in the metabolic syndrome.
AB  - AIMS: The metabolic syndrome is a cluster of cardiovascular risk factors which
      include central obesity, dyslipidaemia, glucose intolerance and hypertension.
      These risk factors are common in patients with growth hormone (GH) deficiency,
      suggesting a role for the somatotropic axis in the development of metabolic
      syndrome. METHODS: We used factor analysis to investigate the relationships
      linking serum levels of GH and insulin-like growth factor I (IGF-I) to metabolic
      syndrome variables (high-density lipoprotein cholesterol, triglycerides, fasting
      glucose, blood pressure and waist circumference). We studied 359 men and 388
      women from the Data from an Epidemiological Study on the Insulin Resistance
      syndrome (DESIR). Their age range was 30-64 years. RESULTS: Three independent
      latent factors explained 61% of the total variance in women and four factors
      explained 73% in men. In both men and women, IGF-I showed a strong positive
      correlation with the lipid factor and a negative correlation with the
      obesity/glucose factor. In women, GH showed a strong negative correlation with
      the obesity/glucose factor but not the lipid factor. In men, GH was unrelated to
      the lipid and obesity/glucose factors. The blood pressure factor was not related
      to GH or IGF-I. In contrast with IGF-I, GH was significantly lower in women with
      metabolic syndrome (1575 +/- 449 pg/ml) than in the other women (2121 +/- 520
      pg/ml, P = 0.002). No significant difference was observed in men for GH or IGF-I.
      CONCLUSION: Our results support a link between the somatotropic axis and several
      features of the metabolic syndrome, and suggest distinct effects of GH and IGF-I
      on these parameters.

PMID- 17535292
TI  - Length of gestation and gender are associated with HLA genotypes at risk for Type
      1 diabetes (Italian DIABFIN 3).
AB  - AIM: The aim of this study, which is part of the ongoing DIABFIN project, was to
      correlate HLA class II genotypes, classified for their effect on susceptibility
      to Type 1 diabetes (T1D), with various risk factors during pregnancy and the
      neonatal period. METHODS: Cord blood was collected from 4349 neonates; 1.0% were
      at high HLA risk (HR), 9.0% at moderate HLA risk (MR), and 90.0% at low HLA risk
      (LR) for T1D. Information about the mother's pregnancy, type of delivery, the
      neonates' clinical features at birth, and family history for autoimmune diseases
      were collected. RESULTS: Significant correlations were found between the
      different HLA risk categories and length of gestation, even when adjusted for
      sex, weight and length at birth of the neonate, birth order and mother's age
      (adjusted P = 0.007). The male : female ratio tended to increase from the LR to
      the HR category, from 1.00 and 1.21, respectively, in the LR and MR groups, to
      1.62 in the HR group (P = 0.05). CONCLUSIONS: Length of gestation is inversely
      correlated with HLA risk categories for T1D. The higher the HLA risk for T1D, the
      shorter the gestational age, especially in male neonates.

PMID- 17535293
TI  - Reduced peripheral blood mitochondrial DNA content is not a risk factor for Type
      2 diabetes.
AB  - AIMS: Mitochondrial depletion in pancreatic beta cells is known to reduce glucose
      stimulated insulin secretion. We aimed to determine whether the offspring of
      patients with early onset Type 2 diabetes had reduced peripheral blood
      mitochondrial content relative to control subjects and whether this could lead to
      a predisposition to type 2 diabetes in later life. METHODS: We measured the
      levels of mitochondria relative to a single copy genomic target by real time
      polymerase chain reaction in a series of peripheral blood samples taken from the
      offspring of Caucasian patients with Type 2 diabetes and matched controls.
      Measures of insulin sensitivity and beta cell function were also taken. RESULTS:
      In contrast with previous studies, mitochondrial DNA content was not decreased in
      the offspring of patients with Type 2 diabetes relative to matched controls in
      our cohort. Conversely, we noted a small proliferation in mitochondrial numbers
      in our case subjects. In agreement with these findings, no correlations with
      either insulin sensitivity or beta cell function were noted. CONCLUSIONS: Our
      results indicate that reduced mitochondrial DNA content in peripheral blood is
      not a risk factor for the development of Type 2 diabetes in the offspring of
      patients with early onset Type 2 diabetes.

PMID- 17535294
TI  - A transition care programme which improves diabetes control and reduces hospital
      admission rates in young adults with Type 1 diabetes aged 15-25 years.
AB  - AIMS: To determine if a transition support programme for young adults with
      diabetes could maintain attendance at a specialist clinic, improve diabetes
      control and reduce acute hospital admissions with diabetic ketoacidosis (DKA) in
      15-25-year-olds with Type 1 diabetes. METHODS: A transition coordinator/diabetes
      educator arranged booking and rebooking of appointments for a young adult
      diabetes clinic based in an adult hospital between July 2001 and March 2006. An
      after-hours phone support service was initiated. Data collected included source
      of referral, frequency of clinic attendance and HbA1c at each visit. Numbers of
      admissions and readmissions with DKA, length of stay and HbA1c on admission were
      recorded. RESULTS: One hundred and ninety-one young adults were referred. HbA1c
      at initial referral was 9.3 +/- 2.17%. HbA1c significantly improved to 8.8 +/-
      1.9% (P < 0.001) after a median of five visits with a statistically significant
      fall in HbA1c of 0.13% per visit (P = 0.01). The greatest improvements were seen
      in those with starting HbA1c > 11% (-2.5 +/- 2.3%, P < 0.001). Eighty-two percent
      had attended appointments in the last 6 months. There was a significant reduction
      in DKA admissions falling by 1/3 (P = 0.05), and in readmissions a significant
      reduction in length of stay (-3.6 days, P = 0.02), over 3.5 years. CONCLUSIONS:
      If young adults are appropriately supported in adult services, clinic attendance
      is maintained, diabetes control is improved and hospital admission rates with DKA
      are reduced. The cost savings from reduced admissions covered the costs of the
      programme.

PMID- 17535295
TI  - Functional analysis of cell-free-produced human endothelin B receptor reveals
      transmembrane segment 1 as an essential area for ET-1 binding and homodimer
      formation.
AB  - The functional and structural characterization of G-protein-coupled receptors
      (GPCRs) still suffers from tremendous difficulties during sample preparation.
      Cell-free expression has recently emerged as a promising alternative approach for
      the synthesis of polytopic integral membrane proteins and, in particular, for the
      production of G-protein-coupled receptors. We have now analyzed the quality and
      functional folding of cell-free produced human endothelin type B receptor samples
      as an example of the rhodopsin-type family of G-protein-coupled receptors in
      correlation with different cell-free expression modes. Human endothelin B
      receptor was cell-free produced as a precipitate and subsequently solubilized in
      detergent, or was directly synthesized in micelles of various supplied mild
      detergents. Purified cell-free-produced human endothelin B receptor samples were
      evaluated by single-particle analysis and by ligand-binding assays. The soluble
      human endothelin B receptor produced is predominantly present as dimeric
      complexes without detectable aggregation, and the quality of the sample is very
      similar to that of the related rhodopsin isolated from natural sources. The
      binding of human endothelin B receptor to its natural peptide ligand endothelin-1
      is demonstrated by coelution, pull-down assays, and surface plasmon resonance
      assays. Systematic functional analysis of truncated human endothelin B receptor
      derivatives confined two key receptor functions to the membrane-localized part of
      human endothelin B receptor. A 39 amino acid fragment spanning residues 93-131
      and including the proposed transmembrane segment 1 was identified as a central
      area involved in endothelin-1 binding as well as in human endothelin B receptor
      homo-oligomer formation. Our approach represents an efficient expression
      technique for G-protein-coupled receptors such as human endothelin B receptor,
      and might provide a valuable tool for fast structural and functional
      characterizations.

PMID- 17535296
TI  - Tumor suppressor p16INK4a--modulator of glycomic profile and galectin-1
      expression to increase susceptibility to carbohydrate-dependent induction of
      anoikis in pancreatic carcinoma cells.
AB  - Expression of the tumor suppressor p16(INK4a) after stable transfection can
      restore the susceptibility of epithelial tumor cells to anoikis. This property is
      linked to increases in the expression and cell-surface presence of the
      fibronectin receptor. Considering its glycan chains as pivotal signals, we
      assumed an effect of p16(INK4a) on glycosylation. To test this hypothesis for
      human Capan-1 pancreatic carcinoma cells, we combined microarray for selected
      glycosyltransferase genes with 2D chromatographic glycan profiling and plant
      lectin binding. Major differences between p16-positive and control cells were
      detected. They concerned expression of beta1,4-galactosyltransferases (down
      regulation of beta1,4-galactosyltransferases-I/V and up-regulation of beta1,4
      galactosyltransferase-IV) as well as decreased alpha2,3-sialylation of O-glycans
      and alpha2,6-sialylation of N-glycans. The changes are compatible with increased
      beta(1)-integrin maturation, subunit assembly and binding activity of the
      alpha(5)beta(1)-integrin. Of further functional relevance in line with our
      hypothesis, we revealed differential reactivity towards endogenous lectins,
      especially galectin-1. As a result of reduced sialylation, the cells' capacity to
      bind galectin-1 was enhanced. In parallel, the level of transcription of the
      galectin-1 gene increased conspicuously in p16(INK4a)-positive cells, and even
      figured prominently in a microarray on 1996 tumor-associated genes and in
      proteomic analysis. The cells therefore gain optimal responsiveness. The
      correlation between genetically modulated galectin-1 levels and anoikis rates in
      engineered transfectants inferred functional significance. To connect these
      findings to the fibronectin receptor, galectin-1 was shown to be co
      immunoprecipitated. We conclude that p16(INK4a) orchestrates distinct aspects of
      glycosylation that are relevant for integrin maturation and reactivity to an
      endogenous effector as well as the effector's expression. This mechanism
      establishes a new aspect of p16(INK4a) functionality.

PMID- 17535297
TI  - Influence of arbuscular mycorrhizal mycelial exudates on soil bacterial growth
      and community structure.
AB  - Plant root systems colonized by arbuscular mycorrhizal (AM) fungi have previously
      been shown to influence soil bacterial populations; however, the direct influence
      of the AM extraradical mycelium itself on bacterial growth and community
      composition is not well understood. In this study, we investigated the effects of
      exudates produced by AM extraradical mycelia on the growth and development of an
      extracted soil bacterial community in vitro. The chemical composition of the
      mycelial exudates was analysed using proton nuclear magnetic resonance
      spectrometry. Following the addition of exudates to a bacterial community
      extracted from soil, bacterial growth and vitality were determined using a
      bacterial vitality stain and fluorescence microscopy. Changes in community
      composition were also analysed at various times over the course of 3 days by
      terminal restriction fragment length polymorphism analysis, in combination with
      cloning and sequencing of 16S rRNA genes. Mycelial exudates increased bacterial
      growth and vitality and changed bacterial community composition. Several
      Gammaproteobacteria, including a taxon within the Enterobacteriaceae, increased
      in frequency of occurrence in response to AM mycelial exudates. This study is the
      first attempt to identify carbohydrates from the extraradical mycelium of an AM
      fungus, and demonstrates the direct effects of mycelial exudates on a soil
      bacterial community.

PMID- 17535298
TI  - Biomineralization of carbonate and phosphate by moderately halophilic bacteria.
AB  - We investigated the precipitation of carbonate and phosphate minerals by 19
      species of moderately halophilic bacteria using media with variable Mg(2+)/Ca(2+)
      ratios. The precipitated minerals were calcite, magnesium (Mg) calcite, and
      struvite (MgNH(4)PO(4) x 6H(2)O) in variable proportions depending on the
      Mg(2+)/Ca(2+) ratio of the medium. The Mg content of the Mg-calcite decreased
      with increasing Ca(2+) concentration in the medium. According to the saturation
      indices, other minerals could also have precipitated. We observed important
      differences between the morphology of carbonate and phosphate, which may help us
      to recognize these minerals in natural systems. We studied the growth and pH
      curves of four bacteria in media specific for carbonate and struvite
      precipitation. We consider the biomineralization processes that produce carbonate
      and phosphate minerals, and propose a hypothesis for the lack of struvite in
      natural environments and ancient rocks.

PMID- 17535299
TI  - Prevalence and distribution of nucleotide sequences typical for pMEA-like
      accessory genetic elements in the genus Amycolatopsis.
AB  - The prevalence and distribution of pMEA-like elements in the genus Amycolatopsis
      was studied. For this purpose, a set of 95 recently isolated Amycolatopsis
      strains and 16 Amycolatopsis type strains were examined for the presence of two
      unique pMEA-sequences (repAM and traJ), encoding proteins essential for
      replication and conjugative transfer. Homologues of repAM and traJ were found in
      10 and 26 of 111 investigated strains, respectively, a result which shows that
      pMEA-like sequences, though not very abundant, can be found in several
      Amycolatopsis strains. Phylogenetic analysis of the deduced RepAM and TraJ
      protein sequences revealed clustering with the protein sequences of either
      pMEA300 or pMEA100. Furthermore, two geographically different populations of pMEA
      like elements were distinguished, one originating in Europe and the other in
      Australia and Asia. Linkage between the distribution of repAM and traJ and the
      chromosomal identifier, the 16S rRNA gene, indicated that these elements
      coevolved with their hosts, suggesting that they evolved in an integrated form
      rather than by horizontal gene transfer of the free replicating form.

PMID- 17535300
TI  - Characterization of epitopes recognized by anti-Streptococcus mutans P1
      monoclonal antibodies.
AB  - Sequences contributing to epitopes recognized by a panel of monoclonal antibodies
      (mAbs) against the Streptococcus mutans surface protein P1 were delineated by
      Western blot and enzyme-linked immunosorbent assay using a battery of deletion
      constructs and recombinant polypeptides. mAbs that recognize complex
      discontinuous epitopes reconstituted by combining the alanine-rich and proline
      rich repeat domains and varying degrees of flanking sequence were identified as
      well as mAbs that bound epitopes contained within contiguous segments of P1.
      Cross-reactivity with SspA and SspB from Streptococcus gordonii is also reported.
      This information enables insight into the structure and function of a
      streptococcal adhesin and its correlates of protection and furthers our
      understanding of the immunomodulatory and bacterial-adherence inhibition
      activities of anti-P1 mAbs.

PMID- 17535301
TI  - DXA scanning in women over 50 years with distal forearm fracture shows
      osteoporosis is infrequent until age 65 years.
AB  - AIMS: Women with distal forearm fracture (DFF) may have low bone mineral density
      (BMD) and merit Dual Energy Xray (DXA) scanning. However patient age at fracture
      and the database for 'healthy' subjects may influence how many have osteoporosis
      and require DXA scans. Osteoporosis prevalence in DFF patients by age was
      investigated using local or nHanes III databases for BMD. METHODS: A total of 186
      women over 50 years consecutively referred with DFF over 1 year were audited
      without exclusion criteria. BMD of L2-4 and femoral neck (Hologic QDR4500A) was
      measured and T- and Z-scores calculated from a local database or nHanes III.
      RESULTS: Of 90 patients aged 50-64 years, 21.1% had femoral neck T-score < -2.5
      and 7.7% < -3.0 (local) and 8.8% and 4.4% respectively (nHanes III). Patients
      aged 65-74 years (n = 61) included 19.7% with T-score < -2.5 (nHanes III = 10%).
      41.2% (nHanes III = 28.6%) of patients > 75 years had femoral neck osteoporosis.
      Including patients with spine T < -2.5 increased the proportion to 31.1% (50-64
      years) and 34.4% (65-74 years) with no extra over 75 years. Weight predicted low
      BMD ineffectively (area under ROC = 70%). CONCLUSION: Osteoporosis is infrequent
      in women with DFF below 65 years. As fracture prevention treatment yields
      significant fracture reduction only in patients with T-score < -2.5, DXA scanning
      below 65 years is not justified. After 65 years scanning is justified at all
      ages, as even in the elderly patients osteoporosis is present in < 50% of
      patients with DFF. Using nHanes III limits the number of DFF patients warranting
      treatment. Low body weight is unreliable for identifying osteoporosis.

PMID- 17535302
TI  - Cataract surgery in previously vitrectomized eyes.
AB  - PURPOSE: To evaluate the results of extracapsular cataract extraction (ECCE) and
      phacoemulsification (PHACO) performed in previously vitrectomized eyes. MATERIAL
      AND METHOD: In this retrospective study, 56 vitrectomized eyes that had ECCE and
      60 vitrectomized eyes that had PHACO were included in the study group while 65
      eyes that had PHACO in the control group. The evaluated parameters were the
      incidence of intra-operative and postoperative complications (IPC) and visual
      outcomes. Chi-squared, independent samples and paired samples tests were used for
      comparing the results. RESULTS: Deep anterior chamber (AC) was significantly more
      common in the PHACO group of vitrectomized eyes (PGVE) and observed in eyes that
      had undergone extensive vitreous removal (p < 0.05). Except for this there were
      no significant differences in the rate of IPC between the ECCE group and the PGVE
      (p > 0.05). Some of the intra-operative conditions such as posterior synechiae,
      primary posterior capsular opacification (PCO) and postoperative complications
      such as retinal detachment (RD), PCO were significantly more common in
      vitrectomized eyes than the controls (p < 0.05). There was no significant
      difference in the visual acuity gain between the ECCE group and the PGVE (p >
      0.05). CONCLUSION: Deep AC is more common in eyes with extensive vitreous removal
      during PHACO than ECCE. Decreasing the bottle height is advised in this case.
      Except for this, the results of ECCE and PHACO are similar in previously
      vitrectomized eyes. Posterior synechiaes, primary and postoperative PCO and RD
      are more common in vitrectomized eyes than the controls.

PMID- 17535303
TI  - Heterotopic gastric mucosa (inlet patch): endoscopic prevalence,
      histopathological, demographical and clinical characteristics.
AB  - OBJECTIVE: Heterotopic gastric mucosa (HGM) is found in the cervical oesophagus,
      just below the upper oesophageal sphincter, and has generally been overlooked by
      endoscopists. The objective of the present study is to determine endoscopic
      prevalence and histopathological and clinical characteristics of HGM and to
      classify patients according to their clinicopathological features. METHOD: A
      total of 911 consecutive patients (436 M and 475 F) who were admitted to our
      Endoscopy Unit were examined. HGM type and the presence of Helicobacter pylori
      (Hp) either in the stomach or in the HGM were histopathologically evaluated.
      RESULTS: Of the 911 patients, 33 (25 M and 8 F) were found to have HGM. HGM
      prevalence was determined to be 3.6%. On the basis of HGM patients' symptoms,
      only dysphagia was significantly correlated with the size of HGM (p < 0.05). Hp
      was positive in 29.2% of HGM. Clinicopathological classification of the patients
      showed that 20 patients were HGM type 1 and 13 were HGM type 2. None of the
      patients had HGM type 3, 4 or 5. CONCLUSION: Prevalence of HGM was 3.6%.
      Dysphagia was found related with the size of HGM. This may be associated with
      larger HGMs' causing more acid secretion.

PMID- 17535304
TI  - Serum nitric oxide levels in children with Wilson's disease.
AB  - BACKGROUND: It is known that the synthesis of nitric oxide (NO) is increased in
      cirrhosis. In humans, NO levels were investigated mostly in adult cirrhotics with
      portal hypertension. Because there is no study investigating NO status in
      childhood cirrhosis and because Wilson's disease (WD) has some specific
      properties due its copper overload with powerful prooxidant action, we aimed to
      determine serum NO levels in children with untreated WD and to investigate the
      probable relationship between NO level and both clinical presentation and the
      severity of the disease. METHODS: Twenty children with newly diagnosed WD and sex
      and age matched 14 healthy children were included. Serum NO levels were
      determined by spectrophotometric method using Griess reaction. RESULTS: Serum NO
      level of children with WD and of healthy children were 156.8 +/- 28.2 and 135.6
      +/- 21.17 micromol/l respectively (p = 0.024). Serum NO level was not different
      in respect with the clinical presentation, such as presence of ascites,
      neurological involvement, cholestasis or haemorrhagic diathesis. Severity of the
      disease did not influence the serum NO level. Serum NO levels of patients with
      low and normal ceruloplasmin levels were not different. CONCLUSION: It was
      demonstrated that serum NO level was higher in children with WD compared to
      healthy children. Because we could not find a correlation between raised NO and
      any clinical or biochemical findings in the present study, we concluded that NO
      could not be used as a prognostic or predicting factor in children with WD.

PMID- 17535305
TI  - Chronic exposure in vivo to thyrotropin receptor stimulating monoclonal
      antibodies sustains high thyroxine levels and thyroid hyperplasia in thyroid
      autoimmunity-prone HLA-DRB1*0301 transgenic mice.
AB  - We have examined the induction of autoimmunity and the maintenance of sustained
      hyperthyroidism in autoimmunity-prone human leucocyte antigen (HLA) DR3
      transgenic non-obese diabetic (NOD) mice following chronic stimulation of the
      thyrotropin receptor (TSHR) by monoclonal thyroid-stimulating autoantibodies
      (TSAbs). Animals received weekly injections over the course of 9 weeks of
      monoclonal antibodies (mAbs) with strong thyroid-stimulating properties.
      Administration of the mAbs KSAb1 (IgG2b) or KSAb2 (IgG2a), which have similar
      stimulating properties but different TSH-binding blocking activity, resulted in
      significantly elevated serum thyroxine (T(4)) levels and thyroid hyperplasia.
      After the first injection, an initial surge then fall in serum T(4) levels was
      followed by sustained elevated levels with subsequent injections for at least 63
      days. Examination of KSAb1 and KSAb2 serum bioactivity showed that the
      accumulation of the TSAbs in serum was related to their subclass half-lives. The
      thyroid glands were enlarged and histological examination showed hyperplastic
      follicles, with minimal accompanying thyroid inflammation. Our results show that
      chronic in vivo administration of mAbs with strong thyroid-stimulating activity
      resulted in elevated T(4) levels, suggesting persistent stimulation without
      receptor desensitization, giving a potential explanation for the sustained
      hyperthyroid status in patients with Graves' disease. Moreover, despite the
      presence of HLA disease susceptibility alleles and the autoimmune prone NOD
      background genes, chronic stimulation of the thyroid gland did not lead to immune
      cell-mediated follicular destruction, suggesting the persistence of
      immunoregulatory influences to suppress autoimmunity.

PMID- 17535306
TI  - Improvement of recipient survival after small size graft liver transplantation in
      rats with preischemic manipulation or administering antisense against nuclear
      factor-kappaB.
AB  - The survival rate of small size graft liver transplantation (SSGLT) in rats is
      inversely related to graft volume. The present study aims to evaluate the
      protective effects of preischemic manipulation (PIM) and oligodeoxynucleotide
      (ODN) antisense against NF-kappaB on graft failure and animal survival. The
      protective effects of PIM and NF-kappaB ODN antisense were investigated in a rat
      SSGLT model. The graft function and survival of recipient animals over 3 weeks
      were monitored, and in situ staining for apoptotic cells in the graft tissue was
      examined. Both PIM and NF-kappaB antisense treatment significantly improved the
      survival of small graft-transplanted rats compared with the SSGLT group, lowered
      serum levels of alanine and aspartate aminotransferases, as well as tumor
      necrosis factor-alpha (TNF-alpha) levels, and minimized apoptotic cell counts in
      the liver sections. Moreover, the enhanced activation of NF-kappaB in the SSGLT
      group was diminished in both PIM and NF-kappaB antisense-treated groups. The
      findings suggest that enhanced NF-kappaB activation and TNF-alpha production may
      be involved in the ischemia/reperfusion-associated small size graft injury, and
      that PIM and antisense against NK-kappaB are effective in the attenuation of the
      small size graft injury, and improve the recipient animal survival.

PMID- 17535307
TI  - Adherence, depression and quality of life in patients on a renal transplantation
      waiting list.
AB  - To study nonadherence, and its relationship with depression and quality of life
      (QOL) in patients on a cadaveric renal transplantation waiting list (RTWL). In 86
      RTWL patients (56 men/30 women), there were 49 nonadherent patients (age, 46.8 +/
      21.8 years) and 37 adherent patients (age, 42.8 +/- 12.1 years). Clinical
      nonadherence was defined as skipping or shortening dialysis sessions,
      interdialytic weight gain (IDWG) of >5.7% body weight, a predialysis potassium
      level of >6 mEq/l and a predialysis phosphate level of >7.5 mg/dl. For each study
      subject, marital status, level of education duration of dialysis, prior renal
      transplantation, IDWG, predialysis blood urea nitrogen (BUN) value and
      creatinine, potassium, phosphate levels were recorded as were scores from the
      short form-36 and Beck depression inventory (BDI). A high IDWG (33.7% of the
      subjects) was the most common nonadherence pattern noted. Age, sex, marital
      status, duration of dialysis, prior transplantation, comorbid conditions the
      predialysis BUN values, the levels of creatinine, potassium, and phosphate were
      not significantly different between the two groups (P > 0.05). The level of
      education was higher in adherent group (P = 0.018). QOL and BDI scores were
      negatively correlated (P = 0.001, r = -0.561). Nonadherent patients had lower QOL
      (P = 0.04) and higher depression scores (P = 0.01) than did adherent patients. Of
      the depressed patients, 77.8% had a comorbid condition. Nonadherence was only
      associated with BDI scores (OR, 2.146; CI, 2.052-2.350; P = 0.002). In dialysis
      patients, close monitoring of adherence, early diagnosis of depression, and the
      treatment of disease may further enhance QOL during the waiting period for a
      cadaveric renal transplant.

PMID- 17535309
TI  - Cultural perspectives of international breast health and breast cancer education.
AB  - PURPOSE: To (a) describe teaching-learning strategies to foster cultural exchange
      among participants in the Train-The-Trainer (TTT) International Breast Health
      Program; (b) describe participants' perceptions of cultural influences on breast
      health and breast cancer; and (c) explore lessons learned about cultural
      influences on breast health TTT educational programs. ORGANIZING CONSTRUCT: The
      TTT curriculum was grounded in the belief that nurses can effectively deliver
      breast health and breast cancer education, that educational programs must be
      culturally relevant and sensitive to the needs of the target population, and that
      an urgent need exists worldwide to reduce the burden of breast cancer. METHODS: A
      total of 32 nurses from 20 countries participated in three TTT programs held
      before the biennial meetings of the International Society of Nurses in Cancer
      Care (ISNCC) since 2000, with follow-up by E-mail survey. Narrative descriptions
      of their perspectives and experiences are reported. RESULTS: Teaching-learning
      strategies incorporated cultural values into a TTT program to engage participants
      in sharing their individual and collective experiences about women with breast
      cancer. CONCLUSIONS: Developing countries are increasingly multicultural.
      Developed countries have large immigrant populations that generally maintain the
      cultural values and practices about breast cancer from the country of origin.
      These "lessons learned" are important in planning other educational programs.

PMID- 17535310
TI  - Fatalism and HIV/AIDS beliefs in rural Mali, West Africa.
AB  - PURPOSE: To examine beliefs about HIV/AIDS of rural Malians and to measure their
      level of fatalism in context of HIV/AIDS and prevention behaviors. DESIGN:
      Descriptive, correlational. METHODS: An AIDS Knowledge and Beliefs survey and the
      Powe Fatalism Inventory (PFI)-HIV/AIDS version were administered to a convenience
      sample of 84 people at three health center maternity clinics in southeastern
      Mali, West Africa. FINDINGS: The sample's HIV/AIDS fatalism mean was 9.2 on a 15
      point scale, with an internal consistency of .89. Health workers and more
      educated participants had significantly lower fatalism scores. Fatalism also
      varied by the combination of gender and ethnicity. People who believed that AIDS
      was not real, was a punishment from God, was fabricated by the West, was a curse,
      and that it was taboo to talk about AIDS had higher fatalism means. None of the
      prevention indicators were significantly related to fatalism scores. CONCLUSIONS:
      These rural Malians had a high overall fatalism mean and their beliefs about AIDS
      based on traditional culture may affect prevention behaviors. More research is
      needed to understand the influence of fatalism on prevention behaviors.

PMID- 17535311
TI  - Predictors of maternal responsiveness.
AB  - PURPOSE: To explore maternal responsiveness in the first 2 to 4 months after
      delivery and to evaluate potential predictors of maternal responsiveness,
      including infant feeding, maternal characteristics, and demographic factors such
      as age, socioeconomic status, and educational level. DESIGN AND METHODS: A cross
      sectional survey design was used to assess the variables of maternal
      responsiveness, feeding patterns, and maternal characteristics in a convenience
      sample of 177 mothers in the first 2 to 4 months after delivery. The 60-item self
      report instrument included scales to measure maternal responsiveness, self
      esteem, and satisfaction with life as well as infant feeding questions and
      sociodemographic items. An online data-collection strategy was used, resulting in
      participants from 41 U.S. states. FINDINGS: Multiple regression analysis showed
      that satisfaction with life, self-esteem, and number of children, but not
      breastfeeding, explained a significant portion of the variance in self-reported
      maternal responsiveness scores. In this analysis, sociodemographic variables such
      as age, education, income, and work status showed little or no relationship to
      maternal responsiveness scores. CONCLUSIONS: This study provides additional
      information about patterns of maternal behavior in the transition to motherhood
      and some of the variables that influence that transition. Satisfaction with life
      was a new predictor of maternal responsiveness. However, with only 15% of the
      variance explained by the predictors in this study, a large portion of the
      variance in maternal responsiveness remains unexplained. Further research in this
      area is needed.

PMID- 17535312
TI  - Identifying risk factors for postpartum tobacco use.
AB  - PURPOSE: To identify factors associated with becoming a mother that may
      contribute to postpartum smoking-related outcomes. DESIGN: Cross-sectional,
      correlational. METHODS: Postpartum women (N=133) who were clients in a nutrition
      supplement program for low-income families responded to questionnaires about
      smoking and early motherhood experiences. Inferential statistical tests included
      hierarchical multiple and logistic regression. FINDINGS: After controlling for
      factors known to be associated with smoking outcomes for the general population,
      factors associated with becoming a mother significantly contributed to the amount
      of explained variance in both postpartum self-efficacy to refrain from smoking
      and smoking within 2 weeks after delivery. CONCLUSIONS: Study findings indicated
      that prenatal intentions about postpartum tobacco use and maternal response to
      infant cry episodes were areas for risk assessment that might lead to effective
      smoking cessation interventions uniquely tailored to women who experience
      becoming a mother.

PMID- 17535313
TI  - Testing an intervention to promote children's adherence to asthma self
      management.
AB  - PURPOSE: To test the hypothesis that compared with the control group, 7 through
      11-year-old children with persistent asthma who received asthma education plus a
      contingency management behavioral protocol would show higher adherence to peak
      expiratory flow (PEF) monitoring for asthma self-management and would report
      fewer asthma episodes. DESIGN AND METHODS: A randomized, controlled trial was
      conducted with 77 children with persistent asthma in a southeastern U.S. state.
      Both the intervention and control groups received instruction on PEF monitoring.
      Only the intervention group received asthma education plus contingency
      management, based on cognitive social learning theory, including self-monitoring,
      a contingency contract, tailoring, cueing, and reinforcement. At-home adherence
      to daily PEF monitoring during the 16-week study was assessed with the AccuTrax
      Personal Diary Spirometer, a computerized hand-held meter. Adherence was measured
      as a percentage of prescribed daily PEF uses at Weeks 4 (baseline), 8
      (postintervention), and 16 (maintenance). RESULTS: At the end of the baseline
      period, the groups did not differ in adherence to daily PEF monitoring nor at
      Week 8. At Week 16, the intervention group's adherence for daily electronically
      monitored PEF was higher than that of the control group. Children in either group
      who were >or= 80% adherent to at least once-daily PEF monitoring during the last
      week of the maintenance period (weeks 8 to 16) were less likely to have an asthma
      episode during this period compared with those who were less adherent.
      CONCLUSIONS: The intervention to teach children to adhere to the recommended
      regimen for managing their asthma at home was effective.

PMID- 17535314
TI  - Reconceptualizing adolescent sexual risk in a parent-based expansion of the
      Theory of Planned Behavior.
AB  - PURPOSE: To expand the theory of planned behavior (TPB) to explicate the
      influence of parents on adolescent behaviors and describe its application to
      adolescent sexual risk behaviors. ORGANIZING CONSTRUCT: Parents have repeatedly
      been shown to be among the most significant influences on adolescents' sexual
      risk-related attitudes, intentions, and behaviors. However, many of the leading
      theoretical frameworks for understanding HIV-related sexual risk behavior are
      individual-level models that do not include important influences outside the
      individual, such as parents and families. FINDINGS AND CONCLUSIONS: The proposed
      expansion of the TPB indicates the conceptual underpinnings for the design of
      family-based prevention programs to reduce HIV-related risk behaviors among
      adolescents. Additional research is needed to examine the predictive validity of
      the expanded model, and instrument development is needed for many of the expanded
      model constructs, most notably the parent constructs.

PMID- 17535315
TI  - Delirium in older patients in surgical intensive care units.
AB  - PURPOSE: To examine the frequency and course of delirium in older adults admitted
      to a surgical intensive care unit (SICU). DESIGN AND METHODS: Prospective,
      observational cohort study of 114 English-speaking participants and their
      surrogates, aged 65 and older, admitted to an SICU, and managed by a surgical
      critical care service. Chart reviews and surrogate interviews were conducted
      within 24 hours of SICU admission to collect information regarding evidence of
      dementia using the short form of the Informant Questionnaire on Cognitive Decline
      in the Elderly. Participants were also screened for delirium daily throughout
      their hospitalization with either the Confusion Assessment Method-ICU (CAM-ICU)
      while in the SICU or the CAM while on medical/surgical units. RESULTS: In this
      population of older adults, 18.4% had evidence of dementia on admission to the
      SICU. Few older adults (2.6%) were admitted to the hospital with evidence of
      preexisting delirium, but 28.3% developed delirium in the SICU and 22.7% during
      the post-SICU period. A total of 52 of 114 (45.6%) participants were delirious
      sometime during their hospital stay or 24 hours before hospital admission.
      Episodes of deep sedation and nonarousal were uncommon, occurring in only 9.7% of
      the sample. CONCLUSIONS: Older adults admitted to SICUs were at high risk for
      developing delirium during hospitalization. Further research is needed to
      elucidate the risk factors for, and outcomes of, delirium in this uniquely
      vulnerable population.

PMID- 17535316
TI  - A psychometric toolbox for testing validity and reliability.
AB  - PURPOSE: To review the concepts of reliability and validity, provide examples of
      how the concepts have been used in nursing research, provide guidance for
      improving the psychometric soundness of instruments, and report suggestions from
      editors of nursing journals for incorporating psychometric data into manuscripts.
      METHODS: CINAHL, MEDLINE, and PsycINFO databases were searched using key words:
      validity, reliability, and psychometrics. Nursing research articles were eligible
      for inclusion if they were published in the last 5 years, quantitative methods
      were used, and statistical evidence of psychometric properties were reported.
      Reports of strong psychometric properties of instruments were identified as well
      as those with little supporting evidence of psychometric soundness. FINDINGS:
      Reports frequently indicated content validity but sometimes the studies had fewer
      than five experts for review. Criterion validity was rarely reported and errors
      in the measurement of the criterion were identified. Construct validity remains
      underreported. Most reports indicated internal consistency reliability (alpha)
      but few reports included reliability testing for stability. When retest
      reliability was asserted, time intervals and correlations were frequently not
      included. CONCLUSIONS: Planning for psychometric testing through design and
      reducing nonrandom error in measurement will add to the reliability and validity
      of instruments and increase the strength of study findings. Underreporting of
      validity might occur because of small sample size, poor design, or lack of
      resources. Lack of information on psychometric properties and misapplication of
      psychometric testing is common in the literature.

PMID- 17535317
TI  - Developing a parsimonious model for predicting completion of advance directives.
AB  - PURPOSE: To develop a theory-based model to assist nurses in promoting self
      determination for completion of an advance directive (AD). DESIGN AND METHODS:
      This descriptive study included data from a convenience sample of 118 community
      dwelling older adults in Tennessee, USA. Multinomial logistic regression was used
      to estimate the influence of 15 factors and covariates on completion of an AD.
      FINDINGS: The parsimonious model had three significant factors: receiving AD
      information; attitude index; and health literacy score. Participants were highly
      likely to complete ADs if they had positive attitudes toward ADs and had received
      information on ADs. As health literacy increased, the likelihood that
      participants completed ADs was reduced. This model explained 25% of the variation
      in AD completion. Chi-square fit for the parsimonious model was highly
      significant. CONCLUSIONS: Of 15 factors and covariates that could influence
      completion of an AD, only receiving information about ADs, having positive
      attitudes toward ADs, and health literacy significantly affected the likelihood
      of participants completing ADs. More study is needed on this model and how nurses
      can assist patients with end-of-life decisions.

PMID- 17535319
TI  - Toward a theory of self-reconciliation following mistakes in nursing practice.
AB  - PURPOSE: To explore nurses' responses to making mistakes in hospital-based
      practice in the US. METHODS: A grounded theory approach was used to explore the
      process that occurs after nurses perceive that they have made mistakes in
      practice. Theoretical sampling was used and data were collected until saturation
      occurred. Ten participants, who were registered nurses, described 17 personal
      mistakes. The mistakes they described occurred in hospitals. All participants
      were practicing nursing either in hospitals or in other work settings. FINDINGS:
      A process of "Self-Reconciliation After Making Mistakes in Hospital Practice" was
      identified, with four distinct categories: reality hitting, weighing in, acting,
      and reconciling. The core category was reconciliation of the self, personally and
      professionally. CONCLUSIONS: This research was a first step toward the
      development of a theory of mistake making in nursing practice. This response to
      making mistakes is consistent with previous research and is related to cognitive
      dissonance theory. The responses to mistakes varied from less healthy responses
      of blaming and silence to healthier responses that included disclosure,
      apologizing, and making amends. Further research to develop the theory and to
      determine helpful interventions is suggested.

PMID- 17535318
TI  - Perspectives of elderly people on advance directives in Japan.
AB  - PURPOSE: To examine perspectives of Japanese elderly people on advance directives
      (ADs) and factors related to positive attitudes toward ADs. METHOD: The data were
      collected by a structured questionnaire from 313 of 565 older adult members of
      senior citizens' centers in two cities in Japan. Survey items pertained to
      demographic characteristics, terminal care preferences, and personal values,
      including autonomy, family function, and religious piety. FINDINGS: Of the 313
      elderly people who completed questionnaires, 72.9% had positive preferences for
      executing living wills. With regard to durable power of attorney for health care,
      62.2% approved of it. The supporters of ADs were more likely to have had
      discussions about terminal care with family members or physicians, experience of
      a family member hospitalized for terminal illness or injury, preferences for life
      sustaining treatments that were self-determined, and personal values such as
      religious piety. The relationship between positive preferences toward durable
      power of attorney for health care and sex, marital status, and living
      arrangements were significant. CONCLUSIONS: Most Japanese older adults in this
      study approved of ADs, and family structure was important to the acceptance of
      designating a proxy. Discussion about end-of-life care and respect for life
      sustaining treatment preferences are important decisions, about the end of life.

PMID- 17535320
TI  - The transition of nurse practitioners to changes in prescriptive authority.
AB  - PURPOSE: To understand nurse practitioners' (NPs) decisions about whether to
      obtain prescriptive authority for controlled substances, to describe NPs'
      experiences with providing or prescribing controlled substances, and to describe
      the relationship between perceived autonomy and prescriptive authority for
      controlled substances. DESIGN AND METHODS: Twelve focus groups were conducted
      with approximately 100 NPs who attended continuing education conferences.
      Discussions were audiotaped and transcribed verbatim. Grounded theory approaches
      were used for data collection and analysis. FINDINGS: A core category of Letting
      go and taking hold characterized Washington State NPs' experience of the
      transition to prescribing schedule II-IV medications. Three dimensions of the
      NPs' transition were Resisting change, Ambivalent about change, and Embracing
      change. CONCLUSIONS: The core category, Letting go and taking hold, indicated how
      transition to a new scope of practice extended beyond successful passage of
      legislation, the importance of examining the nature of professional transition
      that accompanies successful legislative change, and role development as an
      ongoing process throughout one's career in response to changes in scope of
      practice. NPs need preparation for a new scope of practice long before
      legislation actually passes. Revealing and examining this process can facilitate
      the goal of achieving fully autonomous NP practice.

PMID- 17535321
TI  - Relationships between change and organizational culture in hospitals.
AB  - PURPOSE: To define organizational culture in hospitals that have received quality
      certificates and to identify attitudes of healthcare personnel toward change.
      METHODS: The population was all physicians and nurses (N=3,067) employed at four
      private hospitals that have received accreditation or the "ISO" certificate, and
      four public hospitals, all of which were located within Istanbul city limits. A
      proportional sample of 570 participants were selected from the eight hospitals.
      Data-gathering tools were information form, culture scale, and Attitude Against
      Change Scale (AACS). Data were evaluated by using descriptive statistics,
      Cronbach alpha coefficient, Chi-square test, and by t test for dependent groups,
      one-way variance analysis (ANOVA), and Tukey test. FINDINGS: The lowest score
      averages on the AACS were found in those employed in public hospitals, in those
      who perceived top executives as autocrats, and in those who were unwilling to
      participate in quality studies. Participants in a power culture were least open
      to change. CONCLUSIONS: A collaborative culture was the most evident culture in
      private hospitals, but in public hospitals the most dominant culture was a power
      culture.

PMID- 17535322
TI  - The Chinese Nursing Interventions instrument.

PMID- 17535323
TI  - Sexual harassment against nurses in Turkey.
AB  - PURPOSE: To identify the prevalence and sources of sexual harassment against
      nurses in Turkey, its consequences, and factors affecting harassment experiences.
      DESIGN: Descriptive survey. Participants (N=622) were selected from nurses
      working in eight Ministry of Health hospitals in Turkey. METHODS: Participants
      were surveyed with a Sexual Harassment Questionnaire, consisting of the
      sociodemographic characteristics of participants, types of sexual harassment,
      sources, feelings, ramifications, and ways to cope with sexual harassment
      behaviors. Frequency and percentage distributions, chi-square, and logistic
      regression were used for data analysis. FINDINGS: The results showed 37.1% of
      participants had been harassed sexually. Physicians were identified as the
      primary instigators of sexual harassment. The most common reactions against
      harassers were anger and fear; frequently reported negative effects of sexual
      harassment were disturbed mental health function, decline in job performance, and
      headache. "Did nothing" was the coping method used most commonly by the nurses.
      About 80% of sexually harassed nurses did not report the incident of sexual
      harassment to hospital administration. CONCLUSIONS: The lower working status and
      power of nurses in the workplace, poor working conditions in healthcare settings,
      and insufficient administrative mechanisms, including the present law and
      regulations against sexual harassers, were identified as important factors in the
      work environment in Turkey.

PMID- 17535329
TI  - Survival of NobelDirect implants: an analysis of 550 consecutively placed
      implants at 18 different clinical centers.
AB  - BACKGROUND: A recently introduced implant, the NobelDirect (Nobel Biocare AB,
      Goteborg, Sweden), has previously been documented with substantial bone
      resorption in a large number of operated cases. PURPOSE: The aim of this study
      was to evaluate the failure rate of NobelDirect implants in a retrospective
      multicenter survey. MATERIALS AND METHODS: A total of 550 NobelDirect implants
      consecutively placed in over 269 patients at 18 centers were evaluated with
      regard to failure rate after an average follow-up of about 1 year. RESULTS: The
      overall failure percentage was 10.9% (59 failures). The 58 implants not loaded
      directly showed only one failure (1.7%) versus 58 failures (11.8%) of those
      implants that were loaded directly. A chemical x-ray photoelectron spectroscopy
      analysis of an implant from the original batch showed up to 3.5% silicon at parts
      of the implants. A retrieval analysis of one implant removed at 2 years after
      placement demonstrated bone resorption down to the level of the fifth thread.
      CONCLUSIONS: It is concluded that the NobelDirect implant, if placed with a punch
      procedure, ground down in situ, and loaded directly, shows an unusually high
      failure rate at 1 year.

PMID- 17535330
TI  - Turned, machined versus double-etched dental implants in vivo.
AB  - BACKGROUND: Positive effects on the clinical outcome of moderately rough implant
      surfaces are described. Intercomparison of clinical data, however, is rarely
      found. PURPOSE: The aim of this study was to compare the clinical results of two
      macroscopically identical implants, the one with a turned, machined and the other
      with an etched surface. MATERIALS AND METHODS: In a retrospective cohort study,
      the included implants followed the criteria: standard surgical protocol, >12
      months in situ; minimally rough self-threading implants with a turned, machined
      surface (Mk II Nobel Biocare AB, Goteborg, Sweden], n=210); etched implants of
      the same macrodesign (3i Implant Innovations Inc., Palm Beach Gardens, FL, USA],
      n=151), length > or = 10 mm. Clinical data and implant success were rated.
      Resonance frequency analysis (RFA) and Periotest (Siemens AG, Bensheim, Germany)
      were measured and related to the corresponding implant survival rate in the
      respective group. RESULTS: The total number of implants was 361, of which 264
      (73%) were subject to clinical reexamination. RFA and Periotest could be recorded
      in 25% of the implants. Neither clinically relevant nor statistically significant
      differences between the surface designs were found in the RFA (64 +/- 8.6 vs 63
      +/- 9.7), in Periotest (-2 +/- 3.3 vs -1 +/- 5.1), and in mean survival periods
      (49 months, 95% confidence interval CI]: 46-51 months, for the turned vs 46
      months, 95% CI: 43-49 months, for the double-etched implant). After osteoplastic
      procedures, a significantly higher rate of implant losses in the turned, machined
      implant group was observed (17 vs 1) with a mean survival period of 43 (40-46)
      months for the turned and 46 (45-48) months for the double-etched implants.
      CONCLUSION: No difference between implants with two different minimally rough
      surfaces was found. A positive effect of surface roughness is observed in poor
      quality bone, but the pivotal proof of this effect is still lacking.

PMID- 17535331
TI  - Bone response inside free-form fabricated macroporous hydroxyapatite scaffolds
      with and without an open microporosity.
AB  - BACKGROUND: The technique of free-form fabrication enables the production of
      controlled macroporous geometry inside ceramic scaffolds. Using scaffolds with
      identical macropore design makes it possible to study a relevant biological
      response linked to other specific changes of the material. PURPOSE: This study
      investigates the role of open micropores in hydroxyapatite (HA) scaffold during
      early bone healing to quantitatively ascertain whether microporosity in otherwise
      identical macroporous HA scaffolds can influence the bone response in rabbit
      tibia and femur at 6 weeks. MATERIALS AND METHODS: HA scaffolds (O: 3.8 mm) with
      and without microporosity were randomly installed in both cortical and trabecular
      bone sites of New Zealand White rabbits. The animals were sacrificed 6 weeks
      after surgery. Ground sections obtained from en bloc tissues containing scaffold
      and recipient bone were subjected to histological evaluation and
      histomorphometric analysis. RESULTS: Microscopy showed elevated amounts of bone
      ingrowth and bone contact inside the microporous HA (mHA) group as compared with
      non-mHA. CONCLUSION: The current study indicates that the presence of open
      scaffold microporosity in HA, as determined by the fabrication process, enhances
      the ability of ceramic scaffolds to promote bone ingrowth and bone contact.

PMID- 17535332
TI  - Multicenter retrospective study of ITI implant-supported posterior partial
      prosthesis in Jordan.
AB  - PURPOSE: The aim of this multicenter study was to evaluate success and
      restorative problems of ITI (ITI Dental Implant System, Straumann AG, Basel,
      Switzerland) implant-supported posterior partial prostheses in Jordan. MATERIALS
      AND METHODS: One-hundred forty-one ITI implants were placed in the posterior
      region of the mandible or the maxilla in 66 patients at multiple clinical
      practices in Jordan. The age of the patients ranged from 17 to 85 years. The
      implants were retrospectively analyzed from the first date of placement in
      September 1999 until May 2006. Eighty-three implants (58.87%) were placed in the
      mandible, and 58 (41.13%) in the maxilla. The implants were loaded with either
      cement-retained single- or multiple-tooth replacements. RESULTS: Three maxillary
      implants of two male patients have been lost (2.13% of the total and 5.12% of the
      maxillary implants). Failed implants were of wide-neck type with 6-mm lengths.
      Moreover, in another two male patients, two single implants at the maxillary
      premolar region exhibited significant bone loss from the buccal side of the
      implant surface (2-mm bone resorption). Those two implants are still functioning
      and were included in calculating the survival rate but not the success rate.
      Therefore, the cumulative survival rate for both arches and genders was 97.87%
      and that for male patients in the maxillary region was 94.88%. The cumulative
      success rate for both arches and genders was 96.45% and that for the maxillary
      region was 86.21%. The corresponding rates concerning implants in female patients
      and the posterior mandible of both genders were 100% for both survival and
      success rates. Only one crown (mandibular) and another two abutment bridge
      (maxillary) were decemented in different patients (2.13%). CONCLUSIONS: The
      survival and success rates of implants placed in male patients and in the maxilla
      were lower than that of implants placed in female patients and in the mandible.
      Cement-retained restorations showed minimal complications.

PMID- 17535333
TI  - High age at the time of implant installation is correlated with increased loss of
      osseointegrated implants in the temporal bone.
AB  - BACKGROUND: The implant failure rate in temporal bone has been reported to be
      about 5 to 10% over a 10-year period. A number of our elderly patients have shown
      increased failure rates over a long time period, which is the reason for the
      present study. PURPOSE: The aim of the present study was to find out if age is
      correlated with implant failure and to measure blood flow in implant sites.
      MATERIALS AND METHODS: The long-time survival of 131 osseointegrated implants
      installed in the temporal bones of 81 patients was correlated with the age of the
      patient at the time of installation. The blood flow in 37 fixture installation
      sites in 22 patients was recorded by means of laser Doppler flowmetry. RESULTS:
      The mean implant failure rate in the study group was 9.8% after a mean follow-up
      time of 7.6 years. There was a significant increase of implant failure in
      patients above 60 years of age. There was further a trend that implants used for
      the bone-anchored hearing aid were lost to a higher proportion than implants used
      for bone-anchored episthesis. There was also a trend that female patients lost
      fewer implants than males. Blood flow in the temporal bone correlated well with
      the age of the patient in that the highest values were recorded from the youngest
      patients. CONCLUSIONS: Increasing age affects failures of osseointegrated
      implants in the temporal bone. Blood flow is higher in the child's temporal bone,
      a factor that can be of importance to understand why age influences implant
      survival.

PMID- 17535334
TI  - Ultrastructure of the interface between titanium and surrounding tissue in rat
      tibiae--a comparison study on titanium-coated and -uncoated plastic implants.
AB  - PURPOSES: The purposes of this study were to prepare experimental titanium-coated
      plastic implants suitable for electron microscopy examination of the titanium
      bone interface and the response of tissue surrounding titanium, and to
      histologically compare surrounding tissue responses in coated and uncoated
      implants. MATERIALS AND METHODS: Experimental plastic implants were prepared from
      a plastic rod coated with a thin film of titanium. Plastic implants without
      coatings were used as controls. The implants were placed into tibiae of 10-week
      old male rats. The specimens with implants were harvested 4 weeks after placement
      and observed under a light microscope, a transmission electron microscope, and a
      scanning electron microscope. RESULTS: In the transmission electron microscopy,
      the titanium layer of the experimental implant was a uniform layer that was
      approximately 150- to 250-nm wide. The new bone formation was observed around
      both titanium-coated implants and plastic implants. However, there was no direct
      bone contact with the plastic implant. DISCUSSION: The responses of tissue
      surrounding the experimental implants varied. Under an electron microscope, the
      following areas were observed: (1) an area with a direct contact between the
      titanium and bone, (2) an area at the interface where an amorphous layer was
      observed, (3) an area with progressing calcification in the surrounding tissue
      where the cells were adjacent to the titanium surface, and (4) an area in which
      bone resorption and apposition were observed and remodeling was thought to be
      occurring. CONCLUSION: The experimental titanium was homogenous and was
      considered to be highly useful in observing the responses of the surrounding
      tissue to the titanium surface.

PMID- 17535335
TI  - Breast metastasis around dental implants: a case report.
AB  - BACKGROUND: Metastases to the oral cavity and to the jaws are rare; hence, the
      clinical manifestations of the oral metastasis lesion could frequently be
      simulating general pathologic entities, making the diagnosis a challenging
      process to the dental team. Local factors, such as trauma, have been observed to
      facilitate the growth of blood-borne tumors. To this end, surgical procedures
      such as fixture placement might cause cancer cells to spread. PURPOSE: Careful
      clinical examination is a valuable help in diagnosing oral lesions, which can
      improve the quality of life of patients and reduce the risks of oral
      complications. MATERIALS AND METHODS: A female patient was referred to the clinic
      with symptoms of irritation, swelling, and pain associated with implants in the
      mandible and the maxilla. RESULTS: Clinical examination, x-ray, and
      histopathology revealed that the patients suffered from a metastatic lesion,
      primary tumor being an adenocarcinoma of the breast diagnosed at the same time.
      CONCLUSION: Optimal clinical examination in conjunction with radiography and
      histopathology is a necessity in order to discover malignant lesions in time.
      Routine dental check-ups must comprise more thorough soft-tissue examination.

PMID- 17535336
TI  - Immediate placement of implants and appliance in an irradiated patient: a case
      study.
AB  - PURPOSE: The purpose of this study was to evaluate the immediate placement of
      implants and appliance using hyperbaric oxygenation on a 45-year-old male with a
      history of squamous cell carcinoma of the floor of the mouth. MATERIALS: Five
      Nobel Biocare implants between the mental foamina were used along with a course
      of pre- and postsurgical hyperbaric oxygenation. RESULTS: After 39 months, the
      patient is symptom free and shows no signs of rejection. Conclusion Using an
      accepted hyperbaric oxygenation protocol when placing and restoring immediate
      implants in this patient resulted in a successful treatment outcome.

PMID- 17535337
TI  - Non-ST segment elevation acute coronary syndromes: treatment guidelines for the
      nurse practitioner.
AB  - PURPOSE: To increase awareness among nurse practitioners (NPs) of the American
      College of Cardiology (ACC)/American Heart Association (AHA) 2002 guideline
      update for the diagnosis and treatment of acute coronary syndrome, and for
      secondary prevention in patients with unstable angina (UA) and non-ST segment
      elevation myocardial infarction (NSTEMI). DATA SOURCES: ACC/AHA 2002 guideline
      update for the management of patients with UA and NSTEMI, ACC/AHA guidelines for
      patients with coronary and other atherosclerotic vascular disease, 2006 update,
      selected research and clinical articles. CONCLUSIONS: Recent research has shown
      that patients with UA/NSTEMI benefit from the routine, long-term use of dual
      antiplatelet therapy with aspirin and clopidogrel. In suitable patients, outcome
      is also improved by adoption of an early invasive strategy combined with
      aggressive medical therapy. IMPLICATIONS FOR PRACTICE: Familiarity with the
      patient as well as current management recommendations can improve clinical
      outcomes for patients with UA/NSTEMI. Thus, NPs can play a pivotal role in the
      management of coronary disease, both during and following an acute ischemic
      event.

PMID- 17535338
TI  - Caring for patients with allergic rhinitis.
AB  - PURPOSE: Allergic rhinitis (AR) affects up to 40 million Americans, with an
      estimated cost of $2.7 billion per annum. This review discusses several
      therapeutic options that reduce the symptoms of AR, including allergen avoidance,
      antihistamines, intranasal corticosteroids (INS), leukotriene receptor
      antagonists, and immunotherapy. DATA SOURCES: The articles included in this
      review were retrieved by a search of Medline literature on the subjects of AR,
      antihistamines, INS, leukotriene antagonists, and immunotherapy, as well as
      current published guidelines for the treatment of AR. CONCLUSIONS: Allergen
      avoidance is recommended for all patients prior to pharmacologic therapy. Oral
      and nasal H(1)-antihistamines are recommended to alleviate the mild and
      intermittent symptoms of AR, and INS are recommended as the first-line treatment
      choice for mild persistent and more moderate-to-severe persistent AR.
      IMPLICATIONS FOR PRACTICE: There are a number of different types of therapy for
      the management of AR; with so many options available, successful tailoring of
      treatment to suit individual requirements is realistically achievable.

PMID- 17535339
TI  - Use of decision rules for osteoporosis prevention and treatment: implications for
      nurse practitioners.
AB  - PURPOSE: To describe the current literature regarding the benefits of bone
      mineral density (BMD) screening and to discuss clinical decision rules for BMD
      screening. DATA SOURCES: Extensive review of the scientific literature regarding
      osteoporosis, BMD screening, and current clinical decision rules. CONCLUSIONS:
      Osteoporosis is a disease characterized by deterioration of bone and increased
      susceptibility to fractures, crippling, and disfigurement. BMD testing is the
      best predictor for osteoporosis and associated fractures; however, routine global
      BMD testing is cost-prohibitive. A need exists for a selective and practical
      clinical decision rule for referral for testing. IMPLICATIONS FOR PRACTICE:
      Several effective clinical decision rules are presented, and their uses and
      applications are described. The osteoporosis self-assessment tool is recommended
      by the authors because of its predictive power and ease of use.

PMID- 17535340
TI  - Caring for the future: strategies for promoting violence prevention in pediatric
      primary care.
AB  - PURPOSE: To identify strategies that will assist nurse practitioners (NPs) to
      incorporate universal youth violence screening and prevention strategies into
      their practices. DATA SOURCES: Extensive reviews of the extant literature,
      clinical and anecdotal information, and professional experiences and encounters
      were utilized to explore and identify current practice recommendations related to
      youth violence prevention. CONCLUSIONS: NPs' expertise in health promotion makes
      them an important member of interdisciplinary team efforts to prevent youth
      violence. Knowledge of risk factors, appropriately focused assessment, and
      relevant intervention strategies can assist NPs to fulfill a valuable role in
      this critical endeavor. IMPLICATIONS FOR PRACTICE: Recently, there has been an
      increased recognition of the role that healthcare providers at all levels can
      play in decreasing youth violence. A greater emphasis on strategies already
      employed by NPs to promote the development of healthy families can contribute
      greatly to reducing the problem of youth violence. Universal screening for
      warning signs and level of violence risk in youth, as well as utilizing
      appropriate interventions and referrals will provide NPs with the opportunity to
      contribute to this important goal.

PMID- 17535341
TI  - Wegener's granulomatosis: symptoms, diagnosis, and treatment.
AB  - PURPOSE: To provide nurse practitioners with a basic understanding of the
      clinical presentation, diagnosis, diagnostic testing, pharmacological treatment,
      and prevalence of Wegener's granulomatosis (WG). DATA SOURCES: Published research
      and clinical articles, and a case report. CONCLUSIONS: WG is a systemic disease
      characterized by vasculitis, necrosis, and granulomas. The diagnosis of WG is
      difficult, particularly early in the disease process. In order to confirm the
      diagnosis, the patient should undergo specific tests such as antineutrophil
      cytoplasm antibodies, erythrocyte sedimentation rate, C-reactive protein, and
      biopsy of the tissue involved. IMPLICATIONS FOR PRACTICE: The diagnosis of WG is
      often delayed because of the vague symptoms on presentation. Initial symptoms,
      such as chronic fatigue, upper respiratory infection, sinusitis, and otitis media
      are common and may not be alarming. Recognizing symptoms, ordering diagnostic
      tests, and providing appropriate pharmacological therapy is key to diagnosing and
      treating WG.

PMID- 17535342
TI  - Postpartum depression screening by family nurse practitioners.
AB  - PURPOSE: The purpose of the study was to identify whether and how nurse
      practitioners (NPs) screen for postpartum depression, as well as to identify
      factors affecting such screening. DATA SOURCES: Self-report data were gathered
      from 159 questionnaires completed by a convenience sample of family NPs (FNPs) in
      Illinois and Wisconsin during July 2002. CONCLUSIONS: Despite the fact that 84%
      of FNP respondents saw at least one postpartum woman yearly, 42% never screened
      for postpartum depression in any way. The subjects' confidence in their knowledge
      of how to use a screening tool was the single best predictor of screening
      behavior (r= .487). NPs tend to follow clinical practice guidelines, but no
      guidelines exist to address postpartum depression specifically. Screening for
      postpartum depression is not universal, making it likely that prevailing
      estimates of the incidence of this disease are low. IMPLICATIONS FOR PRACTICE: If
      the number of NPs who screen for postpartum depression could be increased, many
      postpartum patients and families could be positively affected. Advanced practice
      nursing education should adequately prepare graduates to screen at-risk patients.
      The development of graduate curricula including thorough units on postpartum
      depression, as well as formulation of clinical practice guidelines for postpartum
      depression, could make great strides toward more and better screening, prompt
      diagnosis, and treatment.

PMID- 17535343
TI  - Advanced practice nurse attitudes toward sex offender patients.
AB  - PURPOSE: To determine advanced practice nurses' (APNs') attitudes and behaviors
      toward patients in their practices who are registered sex offenders. DATA
      SOURCES: An online survey of 300 APN members of a local APN organization asking
      respondents to identify the behavioral actions they were likely to agree or
      disagree with when faced with a scenario of realizing that a sex offender was a
      patient in their practice. Sixty-nine respondents submitted completed surveys.
      CONCLUSIONS: There was an ambiguity of behavioral responses and no consensus
      among APNs on how to respond to the issue of a sex offender patient in a
      healthcare practice. There was also a lack of awareness of whether sex offenders
      were patients in their practice. IMPLICATIONS FOR PRACTICE: The modest number of
      respondents and their demographic homogeneity limit the ability to draw any
      conclusions or generalizations from this study. While awareness of a known sex
      offender in a practice is unlikely to alter direct patient care, it may have an
      impact on office policies and procedures and should be a consideration of all
      involved staff, including providers, ancillary team members, and administrative
      personnel.

PMID- 17535344
TI  - Antibiotic prescribing habits of nurse practitioners treating pediatric patients:
      AntiBUGS pediatrics.

PMID- 17535345
TI  - Normal morphometry of the thoracic aorta in the german shepherd dog: a computed
      tomographic study.
AB  - Computed tomographic images of the thoracic aorta of 14 German shepherd dogs were
      examined in order to determine the morphometry of the thoracic aorta.
      Examinations were carried out in the transverse plane at both intervertebral and
      mid-vertebral levels of each thoracic vertebra between T(5) and T(13). The
      dorsoventral and transversal diameters as well as cross-section area of the
      thoracic aorta were measured. The widest transversal diameter was observed at T(4
      5), whereas the largest dorsoventral diameter was detected at T(5). The maximum
      cross-section area was detected at T(4-5). When dorsoventral and transversal
      diameters were compared between males and females, the aortic diameter was found
      to be smaller in males than in females. Although the shape of the thoracic aorta
      was transversal oval in the majority of the examined females, the shape of the
      thoracic aorta was dorsoventral oval in the majority of the males. There were
      significant differences between all levels measured for transversal (P < 0.001),
      dorsoventral (P < 0.001) diameters and cross-section area (P < 0.001) of the
      thoracic aorta. And there was a significant correlation between the three
      parameters examined. However, the correlation coefficient was highest in females.

PMID- 17535346
TI  - Presence of subepithelial lymphoid nodules in the teat of ewes.
AB  - A total of 87 clinically healthy ovine teats were examined bacteriologically (by
      scraping the mucosa) and histologically. Teats examined were those of lactating
      mammary glands with no bacteria isolated (n = 23); of mammary glands after
      cessation of lactation with no bacteria isolated (n = 25); of lactating mammary
      glands with bacteria isolated (n = 22); and of mammary glands after cessation of
      lactation with bacteria isolated (n = 17). The salient histological feature was
      subepithelial leucocytic infiltration. In teat cisterns, lymphocytes were the
      predominant cell type and in teat ducts, lymphocytes and neutrophils were seen in
      equal proportions. Subepithelial lymphoid nodules, some with germinal centres,
      were detected in 43 (49%) teats. The majority of lymphoid nodules was observed at
      the border between teat duct and teat cistern. Presence of bacteria was
      significantly associated with the presence of leucocytic activity (P < 0.001) and
      with the presence of lymphoid nodules (P = 0.032). We conclude that the presence
      of induced subepithelial lymphoid tissue at the border between teat duct and teat
      cistern appears to be important in protecting the mammary gland during the early
      stages of bacterial invasion. The findings call for further investigations into
      the lymphoid structures of the teat; these should elucidate the role and
      development of mammary mucosa-associated lymphoid tissues and may lead to
      strategies for enhancing non-specific defence mechanisms of the mammary gland.

PMID- 17535347
TI  - Ovarian cysts in MRL/MpJ mice originate from rete ovarii.
AB  - In MRL mice aged more than 1 year, but not in C57BL/6 mice, ovaries had grossly
      visible cysts presenting unilaterally or bilaterally. Postnatally, all MRL mice
      developed ovarian cysts by 8 months of age. Observations by light microscopy,
      including lectin histochemistry, indicated that the cysts sometimes included
      papillomatous tissues located at the hilar region and were similar to the rete
      ovarii system, but not to follicles. Two types of epithelial cells, ciliated and
      non-ciliated, were arranged on the cysts, in which both cell types had many
      microvilli projecting in various directions and random ramifications in the
      cystic lumen. These characteristics suggest that ovarian cysts developing in MRL
      mice originate mostly from the rete ovarii. Cysts derived from the rete ovarii at
      8 months of age were histologically detected in all C3H mice as well as MRL mice,
      with variable incidence in ICR, AKR, CBA/N and ddY, and none in C57L/6, DBA/2,
      BALB and A/J mice. However, measurement of the maximum diameters of the ovarian
      cysts indicated that MRL mice regularly possessed the largest cysts visible to
      the naked eye. This is the first report of ovarian cysts in this inbred strain,
      suggesting that ovarian cysts in MRL mice appear with stable incidence and
      development.

PMID- 17535348
TI  - A case of craniothoracopagus (monocephalus thoracopagus tetrabrachius) in a dog.
AB  - This report describes a case of craniothoracopagus (moncephalus thoracopagus
      tetrabrachius) twin puppies in Ibadan, Nigeria. The conjoined twins were given
      birth to by a 7-year-old bitch that was usually allowed to stray away from home
      in search of food. Deformities of the cardiovascular, digestive musculoskeletal,
      respiratory and urinary systems are reported. This is probably the first report
      of craniothoracopagus twinning in a dog.

PMID- 17535349
TI  - Interaction between chromaffin and sustentacular cells in adrenal medulla of
      viscacha (Lagostomus maximus maximus).
AB  - New evidence provides valuable information about the participation of
      sustentacular cells in chromaffin cell catecholamine secretion. In this process,
      calcium ions play an important role. It has been shown that there is an intense
      ionic traffic between both types of cells. Moreover, sustentacular cells take an
      active part in calcium metabolism, regulating levels of the ion and indirectly,
      the synthesis and release of catecholamines. This background information
      encouraged us to study the sustentacular population of Lagostomus adrenal medulla
      and its morphologic relationship with the chromaffin population. The animals were
      captured, transported to the animal facilities, anaesthetized and killed. The
      adrenal gland was processed by immunohistochemistry using antiserum against S-100
      (subunit alpha and beta), a specific marker. Through the morphological and
      immunohistochemical study, it was found that there are sustentacular cells in
      deferent regions of adrenal medulla, mainly in the basal zone of chromaffin
      cells, which constitute the glomerular structure around blood capillaries.
      Cytoplasmic extentions of sustentacular cells penetrate into chromaffin cells and
      make contact with the basal membrane of the capillary endothelium. The
      relationship among chromaffin cells, capillaries and sustentacular cells suggests
      that they may intervene actively in the adrenal medulla metabolism.

PMID- 17535350
TI  - The distribution and chemical coding of intramural neurons supplying the porcine
      stomach - the study on normal pigs and on animals suffering from swine dysentery.
AB  - The present study was designed to investigate the expression of biologically
      active substances by intramural neurons supplying the stomach in normal (control)
      pigs and in pigs suffering from dysentery. Eight juvenile female pigs were used.
      Both dysenteric (n = 4; inoculated with Brachyspira hyodysenteriae) and control
      (n = 4) animals were deeply anaesthetized, transcardially perfused with buffered
      paraformalehyde, and tissue samples comprising all layers of the wall of the
      ventricular fundus were collected. The cryostat sections were processed for
      double-labelling immunofluorescence to study the distribution of the intramural
      nerve structures (visualized with antibodies against protein gene-product 9.5)
      and their chemical coding using antibodies against vesicular acetylcholine (ACh)
      transporter (VAChT), nitric oxide synthase (NOS), galanin (GAL), vasoactive
      intestinal polypeptide (VIP), somatostatin (SOM), Leu(5)-enkephalin (LENK),
      substance P (SP) and calcitonin gene-related peptide (CGRP). In both inner and
      outer submucosal plexuses of the control pigs, the majority of neurons were SP
      (55% and 58%, respectively)- or VAChT (54%)-positive. Many neurons stained also
      for CGRP (43 and 45%) or GAL (20% and 18%) and solitary perikarya were NOS-, SOM-
      or VIP-positive. The myenteric plexus neurons stained for NOS (20%), VAChT (15%),
      GAL (10%), VIP (7%), SP (6%) or CGRP (solitary neurons), but they were SOM
      negative. No intramural neurons immunoreactive to LENK were found. The most
      remarkable difference in the chemical coding of enteric neurons between the
      control and dysenteric pigs was a very increased number of GAL- and VAChT
      positive nerve cells (up to 61% and 85%, respectively) in submucosal plexuses of
      the infected animals. The present results suggest that GAL and ACh have a
      specific role in local neural circuits of the inflamed porcine stomach in the
      course of swine dysentery.

PMID- 17535351
TI  - Histological organization of collared peccary (Tayassu tajacu) lip.
AB  - Collared peccary (Tayassu tajacu) belongs to the Tayassuidae family that is
      characterized by a dorsal scent gland located in the middle of the hump. It can
      be found from south-west United States to Argentina. It is a very well-adapted
      animal that can survive different environments, having a varied diet. Very little
      morphological information of the animal is available, except that concerning the
      reproductive tract. This study describes the histological organization of the
      collared peccary lip. The lip marks the junction between the integument and
      digestive system. It is lined by skin on the outer surface and mucosa on the
      inner surface. Skin appendages such as hair follicles and glands are usually
      found on the outer surface. The collared peccary's lip shows, on the outer
      surface, simple and sinus hair follicles as well as sebaceous and apocrine sweat
      glands. No salivary gland is found on the inner surface, and deep in the
      connective tissue pacinian corpuscles can be found. The connective tissue is rich
      in collagen and elastic fibres. The collared peccary's lip may be used not only
      for food prehension but also functions as a sensitive structure giving tactile
      input to the central nervous system.

PMID- 17535352
TI  - The external and middle ear of the striped dolphin Stenella coeruleoalba (Meyen
      1833).
AB  - The ear of cetaceans, and especially the middle ear, is very different from that
      of terrestrial mammals and shows specific adaptations to diving. Our research,
      performed on six Striped dolphins (Stenella coeruleoalba) stranded along the
      Italian coasts of the Mediterranean Sea, concentrated on the morphology of the
      external and middle ear of this species. We report the findings using a proper
      Veterinary Anatomical Nomenclature and describe the characteristics of the
      auditory meatus of the external ear and the presence and morphology of the
      erectile tissue in the middle ear. Our anatomical and histological data highlight
      the structure and possible functions of the corpus cavernosum located in the
      middle ear of the Striped dolphin, and suggest a possible role for this structure
      in relation to pressure regulation during diving. Many of our observations
      indicate the existence of an internal regulatory system able to prevent
      barotraumas by regulating pressure and volume inside the middle ear cavity.

PMID- 17535353
TI  - Strain differences in the branching of the sciatic nerve in rats.
AB  - The sciatic nerve in the rat is the site most often used for peripheral nerve
      regeneration studies. The length of sciatic nerve available for research,
      however, depends on the point at which the sciatic nerve divides into the
      peroneal and tibial nerves. In the present study, the hind limbs of 150 adult
      male rats of five different strains (Sprague-Dawley, Fischer 344, Wistar-Han,
      Lewis and Nude) were analysed with regard to femur length, the point at which the
      sciatic nerve divides into the tibial and peroneal nerves, and where these are
      surrounded by the same epineurium, and the point at which they are encased in
      individual epineurial sheaths. The results indicate that the lengths of sciatic
      nerve are fairly constant in all strains of rats. In absolute terms, they amount
      to about one-third of the length of the femur for stretches of undivided sciatic
      nerve, and up to nearly half of the femur length for stretches where the tibial
      and peroneal nerves are already present, but are still enclosed by the same
      epineurium. In 61.7% of the hind limbs examined in Fischer rats, however, no
      sciatic nerve could be seen as such, but only in the form of its successors
      surrounded by the separate epineuria. This makes it highly advisable not to use
      male adult Fischer rats in peripheral nerve regeneration studies with the sciatic
      nerve as the point of focus.

PMID- 17535354
TI  - The orbital Harderian gland of the male atlantic bottlenose dolphin (Tursiops
      truncatus): a morphological study.
AB  - The ultrastructure of the Atlantic Bottlenose dolphin Harderian gland (HG) has
      been described but some questions remain unanswered. The purpose of this work was
      to define the gland's structure, ultrastructure and the differences between cells
      (types I and II) of the male dolphin using optic, fluorescence and electron
      transmission microscopy. Three different cells were observed under optic and
      fluorescence microscopic examination, while only two cell types (types I and II)
      were distinguished by electron transmission microscopy. Type I (oval nuclear
      envelope) exhibited three different cell populations and type II (indented
      nuclear envelope) exhibited two different cell populations. Although, we observed
      both types of vesicles in both types of cells they differed, principally, in
      quantity. The glands also possessed prominent duct systems, with three orders of
      complexity. The dolphin orbital HG appears to function as a mixed heterologous
      gland with two types of cells that exhibit both types of vesicles and other
      distinguishable differences.

PMID- 17535355
TI  - Gross morphological and histological features of larynx, trachea and syrinx in
      Japanese quail.
AB  - This study aimed at observing gross morphological and histological
      characteristics of the larynx, trachea and syrinx in Coturnix coturnix japonicum
      (Japanese quail). Sixteen mature quails were divided into two groups. Eight
      animals were stained with 0.1% methylene blue for 15 min, followed by 50% and 70%
      ethyl alcohol solution for gross morphological examination. For the observation
      of histological characteristics the larynx, trachea and syrinx were fixed in 10%
      formaldehyde and embedded in paraffin. Six-micron sections were stained with
      haematoxylin and eosin. There were three rows of papillae which were located oral
      (one row) and aboral (two rows) aspects of the mound. The cricoid cartilage was
      triangular in shape. Only the inlet of the larynx was covered by the olfactory
      mucosa whereas the rest was covered by the respiratory mucosa. There were 83-91
      tracheal rings which were gradually narrowed from the cranial to the caudal
      direction. No overlapping occurred between the rings. The last few tracheal rings
      did not fuse dorsally and formed the tympanium. The pessulus possessed connection
      with the last tracheal ring and the first bronchial ring. Moreover, it was like a
      semiprism in shape at the region of bifurcation being vertical in direction. The
      syrinx was formed by the paired, C-shaped and incomplete bronchial syringeal
      cartilages. The mucosa of the syrinx was lined with a pseudo-stratified layer of
      prism-shaped epithelium. There were nine or 14 C-shaped cartilaginous primary
      bronchi.

PMID- 17535356
TI  - New alternative methods to teach surgical techniques for veterinary medicine
      students despite the absence of living animals. Is that an academic paradox?
AB  - Due to a raised ethical mentality, veterinary schools are pursuing methods to
      preserve animal corpses used for surgical technique classes in an attempt to
      reduce the use of living animals for teaching. Generally speaking, animal and
      human bodies are usually preserved with 10% aqueous formalin solution especially
      for descriptive anatomy classes. Other possibilities include the use of glycerol,
      alcohol and phenol. At present, new fixatives have been developed to allow a
      better and longer preservation of animal corpses in order to maintain
      organoleptic characteristics, i.e. colour, texture, as close as possible to what
      students will deal with living animals. From 2004, in our college, surgical
      technique classes no longer use living animals for students' training. Instead,
      canine corpses chemically preserved with modified Larssen (MLS) and Laskowski
      (LS) solutions are preferred. The purpose of this study was to investigate
      comparatively the biological quality of preservation of these two solutions and
      to evaluate students' learning and acceptance of this new teaching method.
      Although these fixatives maintain body flexibility, LS solution failed to keep an
      ordinary tissue colouration (cadavers were intensely red) and tissue preservation
      was not adequate. By contrast, MLS solution, however, did not alter the
      colouration of cadavers which was fairly similar to that normally found in living
      animals. A remarkable characteristic was a very strong and unpleasant sugary
      odour in LS-preserved animals and therefore the MLS solution was the elected
      method to preserve cadavers for surgical technique classes. The students'
      feedback to the use of Larssen-preserved cadavers was very satisfactory, i.e.
      96.6% of students were in favour of the use of cadavers for surgical training and
      on average 91.8% (2002-2003) of students preferred the MLS solution as the
      chemical preserver, whereas only 8.2% elected LS solution for teaching purposes.
      From the students' point of view (95.1%) the ideal class would be an initial
      training in MLS cadavers followed by classes with animals admitted to the
      Veterinary Hospital.

PMID- 17535357
TI  - Microvascular architecture of the near-term uterine caruncles in water buffaloes
      (Bubalus bubalis).
AB  - The present investigation was carried out on five near-term pregnant water
      buffaloes for studying the microvascular architecture of the uterine caruncles.
      The vascular casts were obtained by injection of 4:1 mixture of mercox and
      methylmethacrylate through the branches of the uterine arteries. After complete
      polymerization of the plastic, corrosion was conducted in 20% potassium
      hydroxide, then the vessel casts were immersed in distilled water, cut into small
      pieces, sputter coated with gold, and examined by using a scanning electron
      microscope. The buffalo uterine caruncle is highly vascularized through two
      slightly convoluted arteries and a single less tortuous vein. The arteries branch
      into several stem arteries at the base of the uterine caruncle, which follow
      nearly straight course in the primary septa towards the fetal side. During the
      courses of these stem arteries arterioles of variable diameters arise. The
      arterioles run in the secondary and tertiary septae and at this location
      arterioles and venules are connected through a voluminous capillary complex. The
      latter consists of capillaries of greatly variable diameters with vigorous
      coiling and sinusoidally dilated zones. From the capillary complexes the blood is
      driven through postcapillary venules back to the tertiary, secondary and primary
      septa, respectively, and then converge into stem veins which leave the caruncles
      through the branches of the uterine vein.

PMID- 17535358
TI  - A light and scanning electron microscopic study of the epididymis active state of
      the endemic Mexican rodent Peromyscus winkelmanni (Carleton) (Rodentia: Muridae).
AB  - The macroscopic and microscopic anatomy of the epididymis of the sexually mature
      Peromyscus winkelmanni (carleton) was examined using light and scanning electron
      microscopy. The epididymis was divided into three regions: caput, corpus and
      cauda. The epididymal duct was lined with columnar and cubic epithelium with
      stereocilia and covered by a muscular connective tissue sheath. Capillaries
      appear to penetrate directly into the epithelium from the underlying connective
      tissue in the initial segment. The epididymal epithelium presents four cell
      types: principal, basal, apical and clear cells. Based on morphological
      differences (height of epithelial cells, length of the stereocilia, luminal area,
      larger diameter and spermatic index), the epididymis of P. winkelmanni, presents
      seven zones. The stereocilia of the epididymal ducts of zones I, II, IV and V are
      thick and tall, while in zone III they are thin and short. The stereocilia in
      zone VI are thin, while in zone VII they are short but thick. The secretory
      products observed in the lumen of the epididymal ducts have vesicular, granular
      and fibrous form in the seven zones. This study contributes to an understanding
      of the morphofunctional features of the epididymis in sperm maturation in a
      species that shows seasonal reproductive activity.

PMID- 17535359
TI  - What is evidence-based medicine? A personal viewpoint.

PMID- 17535360
TI  - The role of research, evidence and education in optometry: a perspective.
AB  - Eye and health care are and always will be both art and science. The science of
      discovery, its translation to clinical care and the education that necessarily
      follows for practitioners is witnessing remarkable change and increasing impact
      on patient care. An independent and vibrant profession commits to discovery as a
      basis of better patient care; optometry is no exception. Some recent discoveries
      in our field are breathtaking and the increasing awareness in health care,
      including in optometry, of the advantages of accepting the challenge of
      translating these discoveries to patient care is becoming more evident. Health
      care practice is increasingly evidence-based on careful science. The implications
      of evidence-based health care are surprisingly broad, with impact on clinical
      care guidelines, reimbursement, future scope of practice responsibilities and
      education both within our schools of optometry and for our practitioner.

PMID- 17535361
TI  - Implementation of evidence-based practice in optometry.
AB  - Evidence-based practice in health care requires that treatment decisions be
      supported by high-quality clinical evidence, preferably involving well-designed
      large-scale clinical trials of the various treatment options. How does this
      relate to everyday primary-care optometry? This article provides a background to
      the emergence of the 'evidence-based' movement and investigates areas where the
      efficacy of clinical optometry might be improved by an evidence-based approach.
      It is argued that evidence-based practice is appropriate for all aspects of
      optometry but it may be most useful in the selection of treatments with topical
      therapeutic agents and in optometry's growing public health role in the detection
      and management of sight-threatening disease.

PMID- 17535362
TI  - Finding, retrieving and evaluating journal and web-based information for evidence
      based optometry.
AB  - How can optometrists ensure they are basing their advice to patients on the most
      reliable information available? This paper discusses search tools, databases,
      websites and journals, which provide free, full-text, web-based access to
      evidence-based literature. Brief tips on searching these resources are provided
      for the time-poor practitioner or researcher. Criteria, such as credibility,
      currency and bias are used to evaluate written material and will be discussed
      with particular reference to the problems inherent in evaluating web pages.

PMID- 17535363
TI  - Amblyopia treatment: an evidence-based approach to maximising treatment outcome.
AB  - The basis of treatment for amblyopia (poor vision due to abnormal visual
      experience early in life) for 250 years has been patching of the unaffected eye
      for extended times to ensure a period of use of the affected eye. Over the last
      decade randomised controlled treatment trials have provided some evidence on how
      to tailor amblyopia therapy more precisely to achieve the best visual outcome
      with the least negative impact on the patient and the family. This review
      highlights the expansion of knowledge regarding treatment for amblyopia and aims
      to provide optometrists with a summary of research evidence to enable them to
      better treat amblyopia. Treatment for amblyopia is effective, as it reduces
      overall prevalence and severity of visual loss in this population. Correction of
      refractive error alone significantly improves visual acuity, sometimes to the
      point where further amblyopia treatment is not required. Atropine penalisation
      and patch occlusion are effective in treating amblyopia. Lesser amounts of
      occlusion or penalisation have been found to be just as effective as greater
      amounts. Recent evidence has highlighted that occlusion or penalisation in
      amblyopia treatment can create negative changes in behaviour in children and
      impact on family life. These complications should be considered when prescribing
      treatment because they can negatively affect compliance. Studies investigating
      the maximum age at which treatment of amblyopia can still be effective and the
      importance of near activities during occlusion are ongoing.

PMID- 17535364
TI  - Resistance to ocular antibiotics: an overview.
AB  - The introduction of new antibiotic compounds into therapy initiates the
      development of resistance by the target bacteria. Resistance increases the risk
      of treatment failure with potentially serious consequences. Local application of
      antibacterial compounds to the eyes may lead to bacterial resistance in bacterial
      isolates from the eyes. The incidence of resistant strains of common pathogens is
      probably increasing. As compounds can be absorbed into the systemic circulation
      following ocular administration, the subsequent low concentrations in the blood
      could provide the selective pressure for the survival of resistant bacteria in
      the body. Despite this possibility, there are no reports of systemic resistance
      in bacteria following ocular administration of antibacterial compounds. All
      health-care professionals should be concerned about this possibility and continue
      to use these important compounds with respect.

PMID- 17535365
TI  - Age-related maculopathy in the light of ischaemia.
AB  - This manuscript focuses on the pathogenesis of age-related maculopathy (ARM) and
      the documentation of new treatments in ARM. Ischaemia will be given special
      consideration, as it is believed to play a central role in both early ARM and
      late ARM or age-related macular degeneration (AMD). Reduced choroidal and retinal
      blood flow causes ischaemia of Bruch's membrane, retinal pigment epithelium and
      neuroretina in the early course of ARM. This is thought to be the primary trigger
      of the condition. Chronic ischaemia upregulates vascular endothelial growth
      factor (VEGF), which induces abnormal vessel growth in neovascular AMD. The role
      of ischaemia in neovascular AMD is supported by the evidence of effective new
      treatments targeting VEGF.

PMID- 17535366
TI  - Supra-threshold contrast matching and the effects of contrast threshold and age.
AB  - BACKGROUND: The effects of age on contrast threshold are well known but little is
      known about its effect on supra-threshold contrast perception. This study
      examines supra-threshold contrast matching and the effects of age in naive
      observers. METHODS: Two age groups (from 20 to 50 years with 14 subjects and 51
      years and older with 15 subjects) participated in the study. Contrast threshold
      and supra-threshold contrast matching up to 8.53 cycles per degree were measured.
      RESULTS: Both age groups demonstrated some degree of contrast constancy at medium
      and higher contrasts but this was not perfect even at the highest contrast tested
      (55.9 per cent). There was no overall effect of age on supra-threshold contrast
      matching (p = 0.086) but there was an interaction between age and spatial
      frequency (p < 0.001). The plots of matched contrast against standard contrast
      showed that for some spatial frequencies, the slope was significantly different
      from unity, indicating a gain in the visual system for supra-threshold
      perception. This was still true when corrected for threshold differences.
      CONCLUSION: Contrast constancy exists in a larger group of naive subjects of
      different ages but does not perfectly compensate for the differences in
      thresholds. The results are discussed in terms of the currently proposed models
      of contrast perception.

PMID- 17535367
TI  - The visual attentional blink reflects constraints on temporal visual processing,
      not just a lapse of visual memory.
AB  - BACKGROUND: Most theories related to the attentional blink (AB), defined as the
      refractory period of 300 to 500 msecs following a conscious visual
      identification, during which a second detection task is impaired, argue that
      limitations of 'visual working memory' (VWM) underlie the phenomenon rather than
      suppression of attention. The current study examined the relationship between
      performance on an AB task and classical measures of visual and auditory memory
      and executive function (EF). METHODS: Fifty-one adult volunteers completed the AB
      task but only 27 of these also completed an extensive battery of traditional
      measures of short-term and working memory, processing speed and EF. Correlation
      and regression methods were used to analyse the data. RESULTS: Bivariate
      correlation showed a significant relationship between AB duration and non-verbal
      intelligence and processing speed. Multiple regression analysis demonstrated that
      four factors (non-verbal intelligence, letter-number sequencing, visual search
      and visuo-spatial recognition memory) explained 40 per cent of the variance, with
      better reasoning skills and letter-number sequencing associated with a shorter
      AB, and better visuo-spatial recognition memory associated with a longer AB.
      CONCLUSION: The positive beta weight in the model for visuo-spatial recognition
      memory may reflect that the ability to later recall a target depends on its depth
      of encoding. On the other hand, the negative betas in the regression model for
      verbal intelligence and processing speed indicate that AB duration may be a
      potentially useful measure of temporal rate of visual processing. Finally, the
      lack of any relationship between the AB and executive function performance
      measures used suggests that the mechanism of the AB is primarily confined to
      early sensory processing and lower level working memory.

PMID- 17535368
TI  - Evaluation of some factors affecting the agreement between the Proview Eye
      Pressure Monitor and the Goldmann applanation tonometer measurements.
AB  - BACKGROUND: Our aim was to examine whether training level and ocular factors
      could account for part of the difference in intraocular pressure (IOP) measured
      using the Goldmann applanation tonometer (GAT) and Proview Eye Pressure Monitor
      (PPT). METHODS: One hundred and nineteen individuals (238 eyes) were enrolled in
      the study. The mean age was 35.8 years (range 21 to 79). All study participants
      obtained IOP measurements using the PPT after hearing instructions on how to
      perform PPT. Glaucoma patients obtained additional IOP measurements using PPT
      after viewing an instructional video and after 30 days of home use. IOP was also
      measured using the GAT at each experimental session. RESULTS: The difference in
      IOP measured by the GAT and the PPT was 0.55 +/- 3.38 mmHg, 0.17 +/- 3.79 mmHg
      and -1.30 +/- 3.79 mmHg for myopic, emmetropic and hypermetropic groups,
      respectively, which were statistically significant (ANCOVA; p = 0.014). The
      difference in IOP between GAT and PPT was not significantly different for
      measurements obtained after verbal instructions, instructional video or after 30
      days of home use (Repeated-ANCOVA; p = 0.30). The overall agreement between the
      GAT and the PPT was poor. Intra-class correlation coefficient was 0.575, and the
      95% confidence interval (CI) of agreement was -6.93 to +6.73 mmHg. CONCLUSION:
      There was a small systematic difference in IOP measured by the GAT and PPT when
      comparing the different refraction groups; however, this level of difference
      between the groups is unlikely to be of clinical significance. The level of
      training in using the PPT did not influence its measurements. The limits of
      agreement between the PPT and the GAT were wide and long-term use of PPT did not
      improve its agreement.

PMID- 17535369
TI  - The value of contrast sensitivity in diagnosing central serous chorioretinopathy.
AB  - A 39-year-old hyperopic male was referred for laser refractive treatment. In the
      course of the pre-operative evaluation he complained of a recent deterioration of
      vision. The suspicion of unilateral central serous chorioretinopathy (CSCR) was
      confirmed by contrast sensitivity testing and by ocular fundus examination.
      Contrast sensitivity (CS) for six spatial frequencies (1, 2, 4, 8, 12 and 16
      c/deg) was evaluated using Gabor patches of gratings projected on a high
      resolution display by means of a stimulus generator card. Although VA remained
      unaltered, the pattern of contrast sensitivity function varied at different
      stages of CSCR: during the acute stage, performance at all spatial frequencies
      was depressed, while at two-month follow up, intermediate and high spatial
      frequencies were mainly affected. It is concluded that the level of visual
      deficit in CSCR cannot be evaluated by measuring visual acuity. History and
      contrast sensitivity can play a central role in setting the correct diagnosis and
      characterising its stage.

PMID- 17535370
TI  - Fibrillary lines in overnight orthokeratology.
AB  - This case report describes the appearance of fibrillary lines in the anterior
      stroma of a 39-year-old Asian woman wearing overnight orthokeratology (OK)
      lenses. The fibrillary lines were fine, slightly curved and sub-epithelial,
      arranged in a band-like annulus in the corneal mid-periphery. The lines were not
      associated with epithelial staining, although a marked Fischer-Schweitzer corneal
      mosaic was noted after blinking. Fibrillary lines are a relatively common finding
      in normal and keratoconic corneas and have been reported previously accompanying
      OK lens wear. Their origin is unknown and epithelial neural remodelling, corneal
      biomechanical stress and abrupt corneal curvature changes have been suggested as
      contributing factors. The appearance of fibrillary lines in our OK patient had no
      adverse consequences on vision or ocular health, at least in the medium term.

PMID- 17535371
TI  - Ocular therapeutics.

PMID- 17535372
TI  - Professor Marion Edwards.

PMID- 17535376
TI  - Sarcoidosis in the sunburnt country.

PMID- 17535377
TI  - Sarcoidosis in Australia.
AB  - BACKGROUND: The incidence of sarcoidosis in Australia is unknown. The clinical
      features, diagnostic strategy and treatment of sarcoidosis in Australia have been
      poorly documented. METHODS: We analysed the medical records of 122 patients with
      sarcoidosis presenting to a respiratory service, between 1995 and 2005, which
      serves a regional southeastern Australian population of approximately 200,000.
      RESULTS: The incidence of sarcoidosis from 2000 to 2005 remained static and
      ranged from 4.4 to 6.3 patients per 100,000 population. The data showed that 55%
      were women and 28% were current smokers. Systems involved included lung
      parenchyma (66%), thoracic adenopathy (58%), skin (22%), ocular (18%), joint
      (11%), gastrointestinal tract (5%), central nervous system (3%) and
      hypercalcaemia (3%). Fifty-one per cent of patients had an increased serum
      angiotensin-converting enzyme level. The diagnosis was secured based on
      histological confirmation in 69%. Forty-three per cent of the patients were
      treated with oral corticosteroids and 10% with inhaled steroids. CONCLUSION:
      Sarcoidosis in Australia is a multi-system disease of unknown aetiology. This is
      the first reported incidence of sarcoidosis in Australia. The incidence is
      similar to another US-based epidemiological study of a predominately white
      population. The development of a larger multicentre database would assist in the
      identification, clinical description and treatment of sarcoidosis.

PMID- 17535378
TI  - Non-invasive computed tomography angiography in the assessment of coronary stent
      patency: an Australian experience.
AB  - BACKGROUND: This study aimed to evaluate the feasibility and accuracy of 16-slice
      computed tomography (CT) in the assessment of coronary stent patency. CT coronary
      angiography (CA) has a high degree of accuracy in the assessment of coronary
      artery disease compared with invasive selective CA. However, its accuracy in the
      evaluation of stent patency is not well investigated. METHODS: We conducted a
      retrospective observational study of paired CT coronary angiography (CT-CA) and
      invasive fluoroscopic coronary angiography (FCA) in 37 patients with 47 coronary
      stents. CT-CA was carried out with an electrocardiogram-gated 16-slice CT
      (LightSpeed-16, General Electric (GE), WI, USA). Two CT reporters, blinded to the
      FCA findings, assessed CT images for stent patency. A cardiologist blinded to CT
      findings reported FCA. FCA was regarded as the reference standard. RESULTS: A CT
      CA could assess 45 of 47 coronary stents (96%). Non-assessable stents on CT-CA
      were due to motion artefacts and stent-blooming effects. Of those 45 assessable
      stents, CT-CA correctly identified five out of seven stents with binary in-stent
      restenosis (ISR) and 37 of 38 stents without binary ISR. The sensitivity and
      specificity of 16-slice CT in the evaluation of coronary stents for binary ISR
      were 71% (95% confidence interval (CI) (29%, 96%)) and 97% (95%CI (86%, 100%)),
      respectively, exclusive of non-assessable stents. The positive and negative
      predictive values of 16-slice CT were 83% (95%CI (36%, 100%)) and 95% (95%CI
      (83%, 99%)), respectively. CONCLUSION: Sixteen-slice CT has a low sensitivity,
      but very a high specificity when compared with FCA in the evaluation of coronary
      stents for ISR.

PMID- 17535379
TI  - Lower plasma adiponectin is correlated to higher alanine aminotransferase
      independent of metabolic factors and hepatitis B virus carrier status.
AB  - BACKGROUND: Adiponectin has been linked to the metabolic syndrome and coronary
      artery disease in recent years. The animal and human data also suggest that
      adiponectin may be beneficial for liver functions. The aim of this study was to
      investigate the correlation between plasma adiponectin level and liver function
      tests in adults with or without chronic hepatitis B virus (HBV) infection.
      METHODS: We analysed the blood levels of liver enzymes and adiponectin in 140
      apparently healthy adults, including 21 HBV carriers. RESULTS: We found that the
      plasma adiponectin levels were inversely correlated to aspartate aminotransferase
      (r = -0.314, P = 0.000) and alanine aminotransferase (ALT) (r = -0.430, P =
      0.000). Among the HBV carriers, the ALT correlated with the plasma adiponectin
      levels (r = -0.521, P = 0.015). In linear regression models adjusting for age,
      sex and the other metabolic variables, the ALT was independently related to the
      plasma adiponectin levels (beta = -0.371 +/- 0.134, P = 0.007), even in HBV
      carriers (beta = -1.143 +/- 0.482, P = 0.034). The ALT was also independently
      correlated to the plasma adiponectin levels (beta = 0.552 +/- 0.132, P < 0.001)
      with adjustment for age, sex and insulin-resistance index by homeostasis model
      assessment, even in HBV carriers (beta = -1.202 +/- 0.562, P = 0.048). The
      subjects with normal ALT had a significantly higher least square mean of plasma
      adiponectin than those with abnormal ALT (4.01 +/- 0.19 vs 3.30 +/- 0.30, P =
      0.014) with adjustment for age, sex, homeostasis model assessment insulin
      resistance and HBV status. CONCLUSION: ALT was inversely related to adiponectin
      levels, independent of the metabolic factors and HBV status. Whether there is any
      potential prognostic and therapeutic value of adiponectin in human liver diseases
      remains to be investigated.

PMID- 17535380
TI  - Medical aspects of fitness to drive. What do public hospital doctors know and
      think?
AB  - BACKGROUND: In Australia medical practitioners are often required to assume the
      responsibility for assessing fitness to drive. However the clinical practice,
      knowledge and attitudes of doctors with regards to this responsibility are
      unknown. The aim of this study was to determine the clinical practice, knowledge
      and attitudes of public hospital doctors in the area of fitness-to-drive decision
      making. METHODS: A survey of public hospital doctors in Adelaide, South Australia
      was undertaken in 2003, shortly after the promulgation nationwide of guidelines
      to assist in the assessment of patients' fitness to drive. The survey sought
      details on medical practitioners' clinical practice in this regard, as well as
      their knowledge of the guidelines. In addition, it sought their attitudes to
      undertake this responsibility. RESULTS: Eighty-four per cent of respondents had
      at some time in their working career at least discussed the issue of fitness to
      drive with their patients. Seventy per cent acknowledged that they had received
      the recently published guidelines on fitness to drive. Despite this, knowledge of
      the contents of the guidelines was poor. Attitudes to the responsibility were
      equivocal with several significant reservations expressed. CONCLUSION: Public
      hospital doctors in Australia have poor knowledge of the content of published
      guidelines in the area of fitness to drive. If this situation is to be improved,
      alternative approaches to the education of this group with respect to this
      significant public health problem should be considered. Many doctors are
      uncomfortable with their responsibilities in this area and alternative models of
      decision-making should be considered.

PMID- 17535381
TI  - Vitamin D deficiency in general medical inpatients in summer and winter.
AB  - BACKGROUND: Vitamin D deficiency is common in various populations worldwide.
      Adverse effects of vitamin D deficiency are the development of bone disorders;
      however, other diseases such as multiple sclerosis, type 1 diabetes, rheumatoid
      arthritis and certain cancers have also been linked to vitamin D deficiency. The
      general medical inpatient population is a group at increased risk of vitamin D
      deficiency. These patients often have coexistent risk factors for its
      consequences. This study aims to document a point prevalence of vitamin D
      deficiency in this population. METHODS: Two cross-sectional audits of patients
      admitted to general medicine units were carried out--the first in mid-November at
      the end of winter and the second in mid-April and May at the end of summer.
      Information regarding patients' comorbidities, medication usage, previous falls
      and fractures was obtained and serum 25-hydroxyvitamin D, parathyroid hormone and
      calcium levels were measured. RESULTS: A total of 129 patients was studied (65 in
      winter and 64 in summer). Ninety-four patients (74%) had 25-hydroxyvitamin D
      levels < or = 50 nmol/L. Seven patients had severe deficiency (levels < or = 12.5
      nmol/L). Average vitamin D levels were lower at the end of winter (35 vs 43
      nmol/L, P = 0.007). Of the 37 patients receiving vitamin D supplements, 20 (54%)
      had 25-hydroxyvitamin D levels < or = 50 nmol/L. CONCLUSION: Low vitamin D levels
      were common in this general medical inpatient population. The average vitamin D
      level was lower in the patient group tested in November following winter.
      Supplementation of vitamin D did not uniformly prevent deficiency.

PMID- 17535382
TI  - Diabetes: advances in treatment.
AB  - The increasing prevalence of diabetes worldwide is cause for concern both in
      terms of associated morbidity and increasing health costs. This review aims to
      focus on new and emerging treatments for type 1 and type 2 diabetes. There has
      been recent focus on diabetes prevention both for type 1 and type 2 diabetes.
      Prevention programme including lifestyle measures and oral hypoglycaemic agents
      have shown up to 61% reduction in the development of type 2 diabetes in patients
      with impaired glucose tolerance or impaired fasting glucose. Little progress has
      been made to date on type 1 diabetes prevention although current work is focusing
      on T-cell immunomodulation therapy and beta cell regeneration. Management of type
      2 diabetes has been improved by the recent introduction of the peroxisome
      proliferator-activated receptor-gamma agonists and more recently by the incretins
      including glucagons like peptide analogues and dipeptidyl peptidase-4 inhibitors.
      This article focuses on the benefits and restrictions of these new agents. The
      new insulin analogues glargine and detemir have made significant improvements in
      the management of type 1 diabetes both in terms of improvement in glycaemic
      control and in reducing hypoglycaemia rates. Inhaled insulin also shows promise
      for needle-free treatment of diabetes and these insulins are currently undergoing
      phase 3 trials. Insulin infusion pumps are becoming more sophisticated and
      increasingly popular in the management of type 1 diabetes. Many studies have
      shown benefits for improved glycaemic control and reduced rates of hypoglycaemia
      with pump treatment compared with multiple daily injections. Pancreas and islet
      cell transplantation are the subject of ongoing research, but currently require
      immunosuppressive treatment regimes. The main limitation is lack of availability
      of donor pancreases. There is much hope that new treatments outlined in this
      review will result in improved outcomes in the treatment of diabetes.

PMID- 17535383
TI  - Evidence-based guide to perioperative medicine.
AB  - The discipline of perioperative medicine is assuming greater importance as
      increasing numbers of older patients with medical comorbidity undergo complex
      surgical procedures. If patient outcomes and use of limited hospital resources
      are to be optimized, physicians with skills and interest in perioperative risk
      assessment and therapeutic intervention are needed. This systematic review
      attempts to provide an evidence-based update in several key areas in the
      management of the perioperative patient.

PMID- 17535384
TI  - Potentially inappropriate prescribing among Australian veterans and war
      widows/widowers.
AB  - This study examined the extent of potentially inappropriate medicine, as defined
      by explicit criteria, dispensed to Australian veterans using the Repatriation
      Pharmaceutical Benefits Scheme Pharmacy Claims database. Twenty-one per cent of
      the 192,363 veterans aged 70 years, with an eligible gold card, were dispensed at
      least one potentially inappropriate medicine in the first 6 months of 2005. Long
      acting benzodiazepines, amitriptyline, amiodarone, oxybutynin and doxepin were
      the medicines most commonly implicated. Strategies to support quality prescribing
      of medicines to the elderly must include a focus on these medicines.

PMID- 17535385
TI  - Severe hypoglycaemia after long-acting octreotide in a patient with an
      unrecognized malignant insulinoma.
AB  - Insulinomas are the most common hormone-producing pancreatic neuroendocrine
      tumours (NETs), and patients usually present with symptoms secondary to
      hypoglycaemia. Octreotide has been widely used in the symptomatic treatment of
      patients with pancreatic NETs, including insulinomas. We describe a case of a
      patient with a metastatic NET, subsequently identified as a malignant insulinoma,
      who developed severe hypoglycaemia after treatment with long-acting octreotide.

PMID- 17535386
TI  - Use of a functional assay to diagnose protein S deficiency; inappropriate testing
      yields equivocal results.
AB  - Inherited deficiency of protein S (PS) is a rare but accepted risk factor for
      venous thromboembolism. There is accumulating evidence that inherited PS
      deficiency may be associated with a variety of adverse obstetric events. Acquired
      PS deficiency may be caused by a variety of clinical states including normal
      pregnancy. We conducted a retrospective audit of the results of screening for PS
      deficiency through our reference laboratory. The majority of patients in this
      audit with significantly reduced (<50%) free functional PS levels had a major
      confounding factor likely to cause acquired PS deficiency, most frequently
      pregnancy. Recommendations for PS testing for the diagnosis of hereditary PS
      deficiency include deferring testing until at least 40 days post-partum. It
      appears that these recommendations are not being adhered to leading to difficulty
      in the interpretation of results.

PMID- 17535387
TI  - Improving the management of acute coronary syndromes in Australia: translating
      evidence to outcomes.
AB  - Cardiovascular disease imposes a heavy burden of morbidity and mortality on the
      Australian community. This situation is likely to exacerbate as the number of
      elderly Australians increase. Management of acute coronary syndromes (ACS) is
      underpinned by a robust evidence base, which is outlined in clinical practice
      guidelines. Yet, despite wide diffusion of guidelines, many Australians who
      experience acute coronary syndromes do not receive optimal care. This article
      reviews what we have learnt from previous quality improvement initiatives and
      discusses what we need to know to improve acute coronary syndromes management in
      Australia.

PMID- 17535388
TI  - Pulmonary sandstorm.

PMID- 17535389
TI  - Palifermin-induced acanthosis nigricans.

PMID- 17535390
TI  - Ortner's syndrome or cardiovocal hoarseness.

PMID- 17535391
TI  - Acute anaemia in a renal transplant patient.

PMID- 17535392
TI  - Late recurrence of osteosarcoma.

PMID- 17535393
TI  - Reversible autoimmune thyroidiitis and oophoritis in a patient with Addison's
      disease.

PMID- 17535394
TI  - Pulmonary embolization of acrylic cement during percutaneous vertebroplasty.

PMID- 17535395
TI  - "I'm glad I'm not young anymore".

PMID- 17535397
TI  - "I'm glad I'm not young anymore": not.

PMID- 17535398
TI  - Unhealthy lifestyle, statins and the secondary prevention of cardiovascular
      disease.

PMID- 17535399
TI  - TSH concentration within the normal range is associated with cognitive function
      and ADHD symptoms in healthy preschoolers.
AB  - OBJECTIVE: Thyroid hormone concentrations outside the normal range affect brain
      development, but their specific influence on behaviour and mental abilities
      within normal values is unknown. The objective of this study was to investigate
      whether thyroid hormone concentrations are related to neurodevelopment and ADHD
      (attention deficit and hyperactivity disorder) symptoms in healthy preschoolers.
      DESIGN SUBJECTS AND MEASUREMENTS: Children from two general population birth
      cohorts in Menorca (n = 289) and Ribera d'Ebre (n = 53), Spain, were assessed in
      a cross-sectional study at the age of 4. Thyroid hormones (free T4 and T3) and
      TSH concentrations were measured and mental and motor development was assessed
      using McCarthy's scales for neuropsychological outcomes and ADHD-DSM-IV for
      attention deficit and hyperactivity/impulsivity symptoms. RESULTS: Children with
      TSH concentrations in the upper quartile of the normal range performed lower on
      McCarthy's scales and were at higher risk for attention deficit and
      hyperactivity/impulsivity symptoms. In the Menorca cohort, a decrease of 5.8 (P <
      0.05) and 6.9 (P < 0.01) points was observed in memory and quantitative skills,
      respectively. In contrast, high T4 concentrations were associated with decreased
      risk of having 1-5 attention deficit symptoms (odds ratio: 0.25; P < 0.01); these
      findings were observed in both cohorts despite differences in mean TSH
      concentrations. No associations were observed with T3. CONCLUSIONS: Despite being
      within the normal range, high TSH concentrations are associated with a lower
      cognitive function and high TSH and low free T4 with ADHD symptoms in healthy
      preschoolers. Statistically significant differences were observed in the highest
      quartiles of TSH, suggesting a need for re-evaluation of the upper limit of the
      normal TSH range.

PMID- 17535400
TI  - Twenty nail dystrophy trachyonychia: an overview.
AB  - Twenty nail dystrophy (TND) trachyonychia, a fascinating clinical condition, was
      brought to focus 25 years ago. Ever since, it has been sparingly reported.
      Nonetheless, the condition is well-recognized and its diagnosis is made on the
      basis of clinical features characterized by onset in infancy/childhood, and
      occasionally in adults. The lesions are fairly representative, and are
      characterized by the alternating elevation and depression (ridging) and/or
      pitting, lack of luster, roughening likened to sandpaper, splitting, and change
      to a muddy grayish-white color. Dystrophy is prominent. Several modes of
      occurrence have been described including an hereditary component. The
      confirmation of diagnosis is through microscopic pathology corresponding either
      to endogenous eczema/dermatitis, lichen-planus like or psoriasic-form. It is a
      self-limiting condition and may occasionally require intervention.

PMID- 17535401
TI  - Expression of p53 in lesions and unaffected skin of patients with plaque-type and
      guttate psoriasis: a quantitative comparative study.
AB  - Psoriasis is a common inflammatory and hyperproliferative skin disease
      characterized by hyperproliferation of keratinocytes. The pathogenesis of
      psoriasis has yet to be determined. The control of cell growth is a delicately
      balanced process, regulated by external signals or the internal genetic program
      of an individual cell. In psoriasis, these processes are disturbed and some
      candidate genes like p53 are suspected of being involved in the pathogenesis of
      the disease. The p53 protein is essential for the regulation of cell
      proliferation. The study was performed on 32 patients with psoriasis (24 plaque
      type, eight guttate type). Biopsy specimens for immunohistochemical determination
      of p53 protein expression were collected from both the lesional and the
      nonlesional skin sites that were not exposed to sun in all of the patients (n =
      32). Taking the ultraviolet (UV) exposure of the skin into consideration, a third
      skin sample was taken from each patient (n = 7) who had lesions on the sun
      exposed areas. Immunohistochemical assessment of p53 expression in skin was
      determined as p53 protein expression per 1000 cells (keratinocytes). The
      statistical analysis revealed that the expressions of p53 per 1000 cells were
      higher in non-sun-exposed lesional skin than the non-sun-exposed nonlesional
      skin, also in plaque-type psoriasis than guttate-type psoriasis (P = 0.000, P =
      0.046, P = 0.037, respectively). There was a positive correlation between the p53
      expression in non-sun-exposed lesional skin versus expression in sun-exposed
      lesional skin (cubic centimeters = 0.811, P = 0.027). Our results show a stronger
      association of elevated p53 expression with chronic rather than acute
      inflammatory psoriasis. This may indicate a mechanistic difference between plaque
      type and guttate psoriasis. Alternatively, this could reflect a chronological
      course as the disease transitions from an acute to a chronic phase.

PMID- 17535402
TI  - E-dermatology: emails about dermatological diseases on the Internet.
AB  - Today, it is very easy to access information for both doctors and patients thanks
      to the Internet. The number of websites including health information is
      increasing day by day. This study was targeted to retrospectively investigate the
      dermatological questions received by the free consultation page of the health
      site for IsNet customers. The patients were assessed on the aspects of age and
      sex. The diseases were classified by the subject of the questions emailed and on
      what the patient would like to learn. It was also assessed whether the patient
      had seen a doctor before sending the email. The responses of the dermatologist
      were also classified as information on the disease and the treatment. A total of
      607 questions were examined. One hundred and thirteen male and 69 female patients
      disclosed their sexes. Also, only 208 patients stated their age and the mean age
      was 29.3 years. Four hundred and sixty questions were related to the emailer. The
      questions usually asked were about treatment and requests for comprehensive
      information about the disease. The diseases most frequently asked about were:
      acne, hair diseases, pruritus, eczema, seborrheic dermatitis, psoriasis,
      superficial mycoses and vitiligo. Most responses were related to general
      information on diagnosis and treatment options. The Internet is frequently
      preferred for its speed; therefore, users do not give detailed information
      because it is not required. These results show there are differences in the
      intentions of our Internet users and the aims of our health website. In order to
      conduct these kinds of services more efficiently, preparing special forms would
      be useful. These data can be beneficial in the development of e-medicine
      programs.

PMID- 17535403
TI  - Mongolian spots with involvement of mandibular area.
AB  - A 1-year-old boy had grayish pigmentation on the left side of his face over the
      area supplied by the mandibular branch of the trigeminal nerve. Upon further
      examination, the lesion was also found on the left side of the neck, shoulder,
      upper arm, right lower back and buttock. The pigmentation was uniform in
      intensity. This case report demonstrates that Mongolian spots can occur on the
      face in the area supplied by the mandibular branch of the trigeminal nerve. These
      spots should not be misdiagnosed as nevus of Ota.

PMID- 17535404
TI  - Fixed eruption due to quinine: report of two cases.
AB  - Fixed eruption is a characteristic condition with recurrent an erythematous
      macule in the same location. Because fixed eruption is caused by medical drugs in
      the majority of cases, it is not so difficult to identify suspicious material by
      interview. However, it may be difficult in cases in which food additives are
      responsible. We report two rare cases of fixed eruption due to quinine contained
      in tonic water. In case 1, a 37-year-old man had repeated erythema on the same
      sites after drinking a variety of cocktails. We suspected tonic water as the
      causative material. Oral challenge test of tonic water was positive and patch
      test with quinine sulfate was positive also. In case 2, a 24-year-old woman in
      had noticed that her eruption appeared after drinking liquor, especially
      cocktails as in case 1. She was also positive upon an oral challenge test of
      tonic water and in a patch test of quinine sulfate.

PMID- 17535405
TI  - Systemic varicella zoster virus reinfection in a case of angioimmunoblastic T
      cell lymphoma.
AB  - Angioimmunoblastic T-cell lymphoma (AITL) is a rare subtype of peripheral T-cell
      lymphoma that causes immunological disorders such as immunosuppression,
      autoimmune disease-like symptoms and allergy. We report a case of a 67-year-old
      man with AITL who had a serious varicella zoster virus (VZV) reinfection that
      appeared clinically to be varicella. Forty percent of cases of AITL are
      associated with skin rash. A variety of cutaneous manifestations have been
      reported; however, the majority are macropapular eruptions that are often
      diagnosed as drug associated. Our study emphasizes the need to correctly diagnose
      opportunistic infections, such as the varicella that is documented in our
      patient, at early stages in AITL.

PMID- 17535406
TI  - Lipoatrophia semicircularis: a compressive lipoatrophy consecutive to persistent
      mechanical pressure.
AB  - Lipoatrophia semicircularis is an infrequent condition characterized by
      semicircular depressions of the anterolateral aspects of the thighs. The origin
      of this peculiar variant of lipoatrophy is unknown, although repeated mechanical
      trauma on the affected thighs has been advocated in many cases. A 57-year-old
      woman presented with a 1-year history of two bilateral, parallel, symmetric,
      asymptomatic depressions on the anterolateral aspect of her thighs. The patient
      worked as a cashier, permanently seated and almost always wearing trousers. The
      localization of lesions and their linear artifactual appearance perfectly matched
      with the strangling folds formed by trousers while being sat. Echotomographic
      examination revealed a loss of the normal echogenic pattern in the subcutaneous
      tissue of the affected areas. We believe that the anatomical adipose constitution
      of women's thighs predisposes that a persistent mechanical pressure induced by
      wearing trousers while being sat for long periods of time, originates a relative
      impaired circulation on a tenuous perfused tissue, and induces the development of
      lipoatrophia semicircularis.

PMID- 17535407
TI  - Primary localized cutaneous amyloidosis with unusual clinical features in a
      patient with Sjogren's syndrome.
AB  - A 69-year-old woman presented with a 2-year history of an eczematous lesion
      covering the genital area. Histopathological examination showed deposits of
      amorphous, eosinophilic material and an infiltrate of plasma cells through the
      entire dermis into the subcutaneous fatty tissue. Congo red-stained deposits
      showed apple-green birefringence with polarizing microscopy. On
      immunohistochemistry, the deposited material was positively stained with anti
      lambda light chain antibodies but not with anti-lambda light chain. A diagnosis
      of primary localized cutaneous amyloidosis (PLCA) was made, and the patient was
      also diagnosed as having Sjogren's syndrome (SjS) based on clinical and
      laboratory findings. The lesion of PLCA has spontaneously regressed over a period
      of 18 months. We report a unique case of PLCA and SjS that clinically
      demonstrated genital eczematous features and spontaneous involution, and we also
      describe a possible association between PLCA and SjS.

PMID- 17535408
TI  - Eosinophilic pustular folliculitis: the first case associated with hepatitis C
      virus.
AB  - Eosinophilic pustular folliculitis is a rare disorder that is characterized by
      recurrent crops of papules and pustules localized on seborrheic areas of the
      body. The etiopathogenesis of the disease is still unknown, but it has been
      related to infections and immunosuppressive states. This report is the first case
      to be found to be related to hepatitis C virus infection.

PMID- 17535409
TI  - Two cases of pressure ulcer healing after liver transplantation in cirrhosis
      patients.
AB  - We report two cases of pressure ulcers in liver cirrhosis patients. In case 1, a
      64-year-old Japanese woman had suffered from liver cirrhosis caused by hepatitis
      C virus and developed a pressure ulcer on her sacral and coccygeal area due to
      long-term bedrest. After she received a living donor liver transplantation from
      her child, the ulcer healed synchronizing with improvement of serum
      cholinesterase and bilirubin. Likewise, her systemic condition also got much
      better after the transplantation. In case 2, a 53-year-old Japanese man with
      hepatitis B virus cirrhosis and hepatocellular carcinoma developed a pressure
      ulcer on his sacral area. Although he received a living donor liver
      transplantation from his brother, his general status and pressure ulcer were
      fluctuating in conformity with the variance of serum bilirubin. However, at 5
      weeks after the transplantation, the ulcer gradually started improving, entrained
      to serum bilirubin decrease. From these findings, the condition of the pressure
      ulcer in liver cirrhosis patients synchronized with serum bilirubin as well as
      systemic condition, suggesting a possible influence of bilirubin for wound
      healing.

PMID- 17535410
TI  - ERK inhibitor PD98059 promotes the phenotypic and functional maturation of murine
      resident Langerhans cells.

PMID- 17535411
TI  - Juxta-clavicular beaded lines.

PMID- 17535412
TI  - Fixed and soluble immune complexes in the epidermis in Hailey-Hailey disease.

PMID- 17535413
TI  - Complex regional pain syndrome I (reflex sympathetic dystrophy) associated with a
      superficial hand burn from a fan heater.

PMID- 17535414
TI  - Case of Bowen's disease occurring in an old Bacille Calmette-Guerin vaccination
      site.

PMID- 17535415
TI  - Induction of lung lesions in Wistar rats by 4-(methylnitrosamino)-1-(3-pyridyl)-1
      butanone and its inhibition by aspirin and phenethyl isothiocyanate.
AB  - BACKGROUND: The development of effective chemopreventive agents against cigarette
      smoke-induced lung cancer could be greatly facilitated by suitable laboratory
      animal models, such as animals treated with the tobacco-specific lung carcinogen
      4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). In the current study, we
      established a novel lung cancer model in Wistar rats treated with NNK. Using this
      model, we assessed the effects of two chemopreventive agents, aspirin and
      phenethyl isothiocyanate (PEITC), on tumor progression. METHODS: First, rats were
      treated with a single-dose of NNK by intratracheal instillation; control rats
      received iodized oil. The animals were then sacrificed on the indicated day after
      drug administration and examined for tumors in the target organs. PCNA, p63 and
      COX-2 expression were analyzed in the preneoplastic lung lesions. Second, rats
      were treated with a single-dose of NNK (25 mg/kg body weight) in the absence or
      presence of aspirin and/or PEITC in the daily diet. The control group received
      only the vehicle in the regular diet. The animals were sacrificed on day 91 after
      bronchial instillation of NNK. Lungs were collected and processed for
      histopathological and immunohistochemical assays. RESULTS: NNK induced
      preneoplastic lesions in lungs, including 33.3% alveolar hyperplasia and 55.6%
      alveolar atypical dysplasia. COX-2 expression increased similarly in alveolar
      hyperplasia and alveolar atypical dysplasia, while PCNA expression increased more
      significantly in the latter than the former. No p63 expression was detected in
      the preneoplastic lesions. In the second study, the incidences of alveolar
      atypical dysplasia were reduced to 10%, 10% and 0%, respectively, in the aspirin,
      PEITC and aspirin and PEITC groups, compared with 62.5% in the carcinogen-treated
      control group. COX-2 expression decreased after dietary aspirin or aspirin and
      PEITC treatment. PCNA expression was significantly reduced in the aspirin and
      PEITC group. CONCLUSION: (1) A single dose of 25 mg/kg body weight NNK by
      intratracheal instillation is sufficient to induce preneoplastic lesions in
      Wistar rat lungs. (2) COX-2 takes part in NNK-induced tumorigenesis but is not
      involved in proliferation. (3) Aspirin and PEITC have protective effects in the
      early stages of tumor progression initiated by NNK.

PMID- 17535416
TI  - Detection of virus-specific intrathecally synthesised immunoglobulin G with a
      fully automated enzyme immunoassay system.
AB  - BACKGROUND: The determination of virus-specific immunoglobulin G (IgG) antibodies
      in cerebrospinal fluid (CSF) is useful for the diagnosis of virus associated
      diseases of the central nervous system (CNS) and for the detection of a
      polyspecific intrathecal immune response in patients with multiple sclerosis.
      Quantification of virus-specific IgG in the CSF is frequently performed by
      calculation of a virus-specific antibody index (AI). Determination of the AI is a
      demanding and labour-intensive technique and therefore automation is desirable.
      We evaluated the precision and the diagnostic value of a fully automated enzyme
      immunoassay for the detection of virus-specific IgG in serum and CSF using the
      analyser BEP2000 (Dade Behring). METHODS: The AI for measles, rubella, varicella
      zoster, and herpes simplex virus IgG was determined from pairs of serum and CSF
      samples of patients with viral CNS infections, multiple sclerosis and of control
      patients. CSF and serum samples were tested simultaneously with reference to a
      standard curve. Starting dilutions were 1:6 and 1:36 for CSF and 1:1386 and
      1:8316 for serum samples. RESULTS: The interassay coefficient of variation was
      below 10% for all parameters tested. There was good agreement between AIs
      obtained with the BEP2000 and AIs derived from the semi-automated reference
      method. CONCLUSION: Determination of virus-specific IgG in serum-CSF-pairs for
      calculation of AI has been successfully automated on the BEP2000. Current
      limitations of the assay layout imposed by the analyser software should be solved
      in future versions to offer more convenience in comparison to manual or semi
      automated methods.

PMID- 17535417
TI  - The challenges of changing national malaria drug policy to artemisinin-based
      combinations in Kenya.
AB  - BACKGROUND: Sulphadoxine/sulphalene-pyrimethamine (SP) was adopted in Kenya as
      first line therapeutic for uncomplicated malaria in 1998. By the second half of
      2003, there was convincing evidence that SP was failing and had to be replaced.
      Despite several descriptive investigations of policy change and implementation
      when countries moved from chloroquine to SP, the different constraints of moving
      to artemisinin-based combination therapy (ACT) in Africa are less well
      documented. METHODS: A narrative description of the process of anti-malarial drug
      policy change, financing and implementation in Kenya is assembled from
      discussions with stakeholders, reports, newspaper articles, minutes of meetings
      and email correspondence between actors in the policy change process. The
      narrative has been structured to capture the timing of events, the difficulties
      and hurdles faced and the resolutions reached to the final implementation of a
      new treatment policy. RESULTS: Following a recognition that SP was failing there
      was a rapid technical appraisal of available data and replacement options
      resulting in a decision to adopt artemether-lumefantrine (AL) as the recommended
      first-line therapy in Kenya, announced in April 2004. Funding requirements were
      approved by the Global Fund to Fight AIDS, Tuberculosis and Malaria (GFATM) and
      over 60 million US$ were agreed in principle in July 2004 to procure AL and
      implement the policy change. AL arrived in Kenya in May 2006, distribution to
      health facilities began in July 2006 coincidental with cascade in-service
      training in the revised national guidelines. Both training and drug distribution
      were almost complete by the end of 2006. The article examines why it took over 32
      months from announcing a drug policy change to completing early implementation.
      Reasons included: lack of clarity on sustainable financing of an expensive
      therapeutic for a common disease, a delay in release of funding, a lack of
      comparative efficacy data between AL and amodiaquine-based alternatives, a poor
      dialogue with pharmaceutical companies with a national interest in antimalarial
      drug supply versus the single sourcing of AL and complex drug ordering, tendering
      and procurement procedures. CONCLUSION: Decisions to abandon failing monotherapy
      in favour of ACT for the treatment of malaria can be achieved relatively quickly.
      Future policy changes in Africa should be carefully prepared for a myriad of
      financial, political and legislative issues that might limit the rapid
      translation of drug policy change into action.

PMID- 17535418
TI  - The PAMINO-project: evaluating a primary care-based educational program to
      improve the quality of life of palliative patients.
AB  - BACKGROUND: The care of palliative patients challenges the health care system in
      both quantity and quality. Especially the role of primary care givers needs to be
      strengthened to provide them with the knowledge and the confidence of applying an
      appropriate end-of-life care to palliative patients. To improve health care
      services for palliative patients in primary care, interested physicians in and
      around Heidelberg, Germany, are enabled to participate in the community-based
      program 'Palliative Medical Initiative North Baden (PAMINO)' to improve their
      knowledge in dealing with palliative patients. The impact of this program on
      patients' health and quality of life remains to be evaluated. METHODS/DESIGN: The
      evaluation of PAMINO is a non-randomized, controlled study. Out of the group of
      primary care physicians who took part in the PAMINO program, a sample of 45
      physicians and their palliative patients will be compared to a sample of
      palliative patients of 45 physicians who did not take part in the program. Every
      four weeks for 6 months or until death, patients, physicians, and the patients'
      family caregivers in both groups answer questions to therapy strategies, quality
      of life (QLQ-C15-PAL, POS), pain (VAS), and burden for family caregivers (BSFC).
      The inclusion of physicians and patients in the study starts in March 2007.
      DISCUSSION: Although participating physicians value the increase in knowledge
      they receive from PAMINO, the effects on patients remain unclear. If the
      evaluation reveals a clear benefit for patients' quality of life, a larger-scale
      implementation of the program is considered. TRIAL REGISTRATION: The study was
      registered at 'current controlled trials (CCT)', registration number:
      ISRCTN78021852.

PMID- 17535419
TI  - Health care in Bosnia and Herzegovina before, during, and after 1992-1995 war: a
      personal testimony.
AB  - Market-based health care reform during democratic transition in Bosnia and
      Herzegovina was complicated by the 1992-1995 war, that devastated the country and
      greater part of its health care infrastructure. The course of the transition and
      consequences of war for the health system and health professionals are presented
      here from the perspective of the author. The description of real-life situations
      and their context is used to illustrate the problems physicians, as well as
      international community, were faced with and how they tried to cope with them
      during and after the war. Speaking openly about the mistakes that were made in
      those times is the first step in preventing them from happening again and an
      invitation for exchange of opinions and open academic discussion.

PMID- 17535420
TI  - Clouded leopard phylogeny revisited: support for species recognition and
      population division between Borneo and Sumatra.
AB  - BACKGROUND: The clouded leopard (Neofelis nebulosa) is one of the least known cat
      species and depletion of their forested habitats puts it under heavy pressure.
      Recently reclassification of Bornean clouded leopards (N. nebulosa diardi) to
      species level (N.diardi) was suggested based on molecular and morphological
      evidence. Since the genetic results were based solely on three Bornean samples we
      re-evaluated this partition using additional samples of Bornean clouded leopards
      (N = 7) and we were also able to include specimens from Sumatra (N = 3), which
      were lacking in previous analysis. RESULTS: We found strong support for the
      distinction between N. nebulosa and N. diardi based on three fragments of mtDNA
      (900 bp) and 18 microsatellites. Forty-one fixed mitochondrial nucleotide
      differences and non-overlapping allele sizes in 8 of 18 microsatellite loci
      distinguished N. nebulosa and N. diardi. This is equivalent to the genetic
      divergence among recognized species in the genus Panthera. Sumatran clouded
      leopards clustered with specimens from Borneo, suggesting that Sumatran
      individuals also belong to N. diardi. Additionally, a significant population
      subdivision was apparent among N. diardi from Sumatra and Borneo based on mtDNA
      and microsatellite data. CONCLUSION: Referring to their origin on two Sunda
      Islands we propose to give N. diardi the common name "Sundaland clouded leopard".
      The reduced gene flow between Borneo and Sumatra might suggest the recognition of
      two subspecies of N. diardi. Based on this reclassification of clouded leopards
      not only species, but also the populations on Borneo and Sumatra should be
      managed separately and a higher priority should be placed to protect the
      different populations from extinction.

PMID- 17535421
TI  - Organizational role stress among medical school faculty members in Iran: dealing
      with role conflict.
AB  - BACKGROUND: Little research has been conducted to investigate role stress
      experienced by faculty members in medical schools in developing countries. This
      becomes even more important when the process of reform in medical education has
      already taken place, such as the case of Iran. The objectives of this study were
      to investigate and assess the level and source of role-related stress as well as
      dimensions of conflict among the faculty members of Iranian medical schools.
      Variables like the length of academic work, academic rank, employment position,
      and the departments of affiliation were also taken into consideration in order to
      determine potentially related factors. METHODS: A survey was conducted at three
      different ranks of public medical schools. The validated Organizational Role
      Stress Scale was used to investigate the level of role stress and dimensions of
      role conflict among medical faculty members. The response rate was 66.5%.
      RESULTS: The findings show that role stress was experienced in high level among
      almost all faculty members. All three studied medical schools with different
      ranks are threatened with relatively the same levels of role stress. Specific
      differences were found among faculty members from different disciplines, and
      academic ranks. Also having permanent position and the length of services had
      significant correlation with the level of role stress. The major role- related
      stress and forms of conflict among faculty members were role overload, role
      expectation conflict, inter-role distance, resource inadequacy, role stagnation,
      and role isolation. CONCLUSION: The most role-related stressors and forms of
      conflict among faculty members include too many tasks and everyday work load;
      conflicting demands from colleagues and superiors; incompatible demands from
      their different personal and organizational roles; inadequate resources for
      appropriate performance; insufficient competency to meet the demands of their
      role; inadequate autonomy to make decision on different tasks; and a feeling of
      underutilization. The findings of this study can assist administrators and policy
      makers to provide an attractive working climate in order to decrease side effects
      and consequences of role stress and to increase productivity of faculty members.
      Furthermore, understanding this situation can help to develop coping strategies
      in order to reduce role-related stress.

PMID- 17535423
TI  - False positive PCR detection of Tropheryma whipplei in the saliva of healthy
      people.
AB  - BACKGROUND: Tropheryma whipplei, the agent of Whipple's disease (WD), has been
      recently isolated and the genomes of two isolates have been fully sequenced.
      Previous diagnosis tools for the diagnosis of the disease used sequence analysis
      of the 16S rRNA gene. Using this target gene, the high percentage of detection of
      the bacterium in saliva of healthy people was in contrast to the negative results
      obtained with specific target genes. The aim of our study was to compare
      previously published primers targeting the 16S rRNA gene to real-time PCR with
      Taqman* probes targeting specific repeat genes only found in the genome of T.
      whipplei in a series of 57 saliva from healthy people. RESULTS: Although the
      specific real-time PCR assays with both primers and probes were negative for all
      the samples, 13 out of 57 samples were positive with different primers previously
      reported targeting the 16S rRNA gene. Among the positive samples, 8 yielded a 231
      bp sequence that was 99.1% identical to that of Actinomyces odontolyticus, 2
      yielded a 226-bp that was 99.6% identical to that of A. turicensis, and 3 yielded
      a 160-bp sequence that was 98.5% identical to that of Capnocytophaga gingivalis.
      We found that the C. gingivalis and A. odontolyticus 16S rRNA sequences obtained
      in our study share more than 80% homology with the corresponding 16S rRNA
      sequences of the T. whipplei genomes especially at 5' and 3' end. CONCLUSION:
      Asymptomatic carriers of T. whipplei in saliva may exist but their prevalence is
      much lower than those previously reported. Testing the specificity of designed
      primers is critical to avoid false positive detection of T. whipplei. In atypical
      case we recommend to test two different specific target genes before concluding.

PMID- 17535422
TI  - Intrahepatic cholestasis of pregnancy.
AB  - Intrahepatic cholestasis of pregnancy (ICP) is a cholestatic disorder
      characterized by (i) pruritus with onset in the second or third trimester of
      pregnancy, (ii) elevated serum aminotransferases and bile acid levels, and (iii)
      spontaneous relief of signs and symptoms within two to three weeks after
      delivery. ICP is observed in 0.4-1% of pregnancies in most areas of Central and
      Western Europe and North America, while in Chile and Bolivia as well as
      Scandinavia and the Baltic states roughly 5-15% and 1-2%, respectively, of
      pregnancies are associated with ICP. Genetic and hormonal factors, but also
      environmental factors may contribute to the pathogenesis of ICP. Intrahepatic
      cholestasis of pregnancy increases the risk of preterm delivery (19-60%),
      meconium staining of amniotic fluid (27%), fetal bradycardia (14%), fetal
      distress (22-41%), and fetal loss (0.4-4.1%), particularly when associated with
      fasting serum bile acid levels > 40 micromol/L. The hydrophilic bile acid
      ursodeoxycholic acid (10-20 mg/kg/d) is today regarded as the first line
      treatment for intrahepatic cholestasis of pregnancy. Delivery has been
      recommended in the 38th week when lung maturity has been established.

PMID- 17535424
TI  - Reliability of voluntary step execution behavior under single and dual task
      conditions.
AB  - BACKGROUND: The current study investigated the repeatability (test-retest
      reliability) of ground reaction force parameters recorded during a voluntary step
      execution under single (motor task) and dual task (motor and cognitive task)
      conditions for healthy adults and elderly individuals as well as the number of
      trials required to produce repeatable results. METHODS: Twenty-four healthy
      adults (21-63 years old) and 16 elderly adults (66-87 years) performed a
      voluntary rapid step execution following a tap on their heel while standing on a
      force platform under single and dual task conditions on three separate occasions.
      The first two tests were performed 30-60 minutes apart and the third test was
      performed a week later. Variables analyzed from the ground reaction force data
      included onset latency of step initiation (initiation phase), preparation and
      swing phases, foot-off and foot-contact times. RESULTS: Intraclass correlation
      coefficients (ICC(2,1)) were good to excellent across all parameters and test
      conditions for the pooled population and for elderly (0.74-0.92 and 0.62-0.88,
      respectively) except for the swing phase duration where lower values were seen
      (0.54-0.60 and 0.32-0.64 respectively). Values were similar under single and dual
      task conditions. CONCLUSION: A voluntary step execution test, performed under
      single and dual task conditions especially foot-off and foot-contact times, is a
      reliable outcome measure that may be a useful tool to asses dynamic balance
      function for diagnostic purposes as well as clinical intervention trials.

PMID- 17535425
TI  - Inhibition of apoptosis prevents West Nile virus induced cell death.
AB  - BACKGROUND: West Nile virus (WNV) infection can cause severe meningitis and
      encephalitis in humans. Apoptosis was recently shown to contribute to the
      pathogenesis of WNV encephalitis. Here, we used WNV-infected glioma cells to
      study WNV-replication and WNV-induced apoptosis in human brain-derived cells.
      RESULTS: T98G cells are highly permissive for lytic WNV-infection as demonstrated
      by the production of infectious virus titre and the development of a
      characteristic cytopathic effect. WNV replication decreased cell viability and
      induced apoptosis as indicated by the activation of the effector caspase-3, the
      initiator caspases-8 and -9, poly(ADP-ribose)polymerase (PARP) cleavage and the
      release of cytochrome c from the mitochondria. Truncation of BID indicated cross
      talk between the extrinsic and intrinsic apoptotic pathways. Inhibition of the
      caspases-8 or -9 inhibited PARP cleavage, demonstrating that both caspases are
      involved in WNV-induced apoptosis. Pan-caspase inhibition prevented WNV-induced
      apoptosis without affecting virus replication. CONCLUSION: We found that WNV
      infection induces cell death in the brain-derived tumour cell line T98G by
      apoptosis under involvement of constituents of the extrinsic as well as the
      intrinsic apoptotic pathways. Our results illuminate the molecular mechanism of
      WNV-induced neural cell death.

PMID- 17535426
TI  - Designing and conducting tabletop exercises to assess public health preparedness
      for manmade and naturally occurring biological threats.
AB  - BACKGROUND: Since 2001, state and local health departments in the United States
      (US) have accelerated efforts to prepare for high-impact public health
      emergencies. One component of these activities has been the development and
      conduct of exercise programs to assess capabilities, train staff and build
      relationships. This paper summarizes lessons learned from tabletop exercises
      about public health emergency preparedness and about the process of developing,
      conducting, and evaluating them. METHODS: We developed, conducted, and evaluated
      31 tabletop exercises in partnership with state and local health departments
      throughout the US from 2003 to 2006. Participant self evaluations, after action
      reports, and tabletop exercise evaluation forms were used to identify aspects of
      the exercises themselves, as well as public health emergency responses that
      participants found more or less challenging, and to highlight lessons learned
      about tabletop exercise design. RESULTS: Designing the exercises involved
      substantial collaboration with representatives from participating health
      departments to assure that the scenarios were credible, focused attention on
      local preparedness needs and priorities, and were logistically feasible to
      implement. During execution of the exercises, nearly all health departments
      struggled with a common set of challenges relating to disease surveillance,
      epidemiologic investigations, communications, command and control, and health
      care surge capacity. In contrast, performance strengths were more varied across
      participating sites, reflecting specific attributes of individual health
      departments or communities, experience with actual public health emergencies, or
      the emphasis of prior preparedness efforts. CONCLUSION: The design, conduct, and
      evaluation of the tabletop exercises described in this report benefited from
      collaborative planning that involved stakeholders from participating health
      departments and exercise developers and facilitators from outside the
      participating agencies. While these exercises identified both strengths and
      vulnerabilities in emergency preparedness, additional work is needed to develop
      reliable metrics to gauge exercise performance, inform follow-up action steps,
      and to develop re-evaluation exercise designs that assess the impact of post
      exercise interventions.

PMID- 17535427
TI  - Dynamics of adipogenic promoter DNA methylation during clonal culture of human
      adipose stem cells to senescence.
AB  - BACKGROUND: Potential therapeutic use of mesenchymal stem cells (MSCs) is likely
      to require large-scale in vitro expansion of the cells before transplantation.
      MSCs from adipose tissue can be cultured extensively until senescence. However,
      little is known on the differentiation potential of adipose stem cells (ASCs)
      upon extended culture and on associated epigenetic alterations. We examined the
      adipogenic differentiation potential of clones of human ASCs in early passage
      culture and upon senescence, and determined whether senescence was associated
      with changes in adipogenic promoter DNA methylation. RESULTS: ASC clones cultured
      to senescence display reduced adipogenic differentiation capacity in vitro, on
      the basis of limited lipogenesis and reduced transcriptional upregulation of
      FABP4 and LPL, two adipogenic genes, while LEP and PPARG2 transcription remains
      unaffected. In undifferentiated senescent cells, PPARG2 and LPL expression is
      unaltered, whereas LEP and FABP4 transcript levels are increased but not in all
      clones. Bisulfite sequencing analysis of DNA methylation reveals overall relative
      stability of LEP, PPARG2, FABP4 and LPL promoter CpG methylation during
      senescence and upon differentiation. Mosaicism in methylation profiles is
      maintained between and within ASC clones, and any CpG-specific methylation change
      detected does not necessarily relate to differentiation potential. One exception
      to this contention is CpG No. 21 in the LEP promoter, whose senescence-related
      methylation may impair upregulation of the gene upon adipogenic stimulation.
      CONCLUSION: Senescent ASCs display reduced in vitro differentiation ability and
      transcriptional activation of adipogenic genes upon differentiation induction.
      These restrictions, however, cannot in general be attributed to specific changes
      in DNA methylation at adipogenic promoters. There also seems to be a correlation
      between CpGs that are hypomethylated and important transcription factor binding
      sites.

PMID- 17535428
TI  - HTLV-1 Tax mutants that do not induce G1 arrest are disabled in activating the
      anaphase promoting complex.
AB  - HTLV-1 Tax is a potent activator of viral transcription and NF-kappaB. Recent
      data indicate that Tax activates the anaphase promoting complex/cyclosome (APC/C)
      ahead of schedule, causing premature degradation of cyclin A, cyclin B1, securin,
      and Skp2. Premature loss of these mitotic regulators is accompanied by mitotic
      aberrations and leads to rapid senescence and cell cycle arrest in HeLa and S.
      cerevisiae cells. Tax-induced rapid senescence (tax-IRS) of HeLa cells is
      mediated primarily by a dramatic stabilization of p27KIP and is also accompanied
      by a great surge in the level of p21CIP1mRNA and protein. Deficiencies in p27KIP
      prevent Tax-IRS. A collection of tax point mutants that permit normal growth of
      S. cerevisiae have been isolated. Like wild-type tax, many of them (C23W, A108T,
      L159F, and L235F) transactivate both the HTLV-LTR and the NF-kappaB reporters.
      One of them, V19M, preferentially activates NF-kappaB, but is attenuated for LTR
      activation. None of the mutants significantly elevated the levels of p21CIP1and
      p27KIP1, indicating that the dramatic surge in p21CIP1/WAF1and p27KIP 1induced by
      Tax is brought about by a mechanism distinct from NF-kappaB or LTR activation.
      Importantly, the ability of these mutants to activate APC/C is attenuated or
      abrogated. These data indicate that Tax-induced rapid senescence is causally
      associated with APC/C activation.

PMID- 17535429
TI  - Differences in the quality of primary medical care for CVD and diabetes across
      the NHS: evidence from the quality and outcomes framework.
AB  - BACKGROUND: Health policy in the UK has rapidly diverged since devolution in
      1999. However, there is relatively little comparative data available to examine
      the impact of this natural experiment in the four UK countries. The Quality and
      Outcomes Framework of the 2004 General Medical Services Contract provides a new
      and potentially rich source of comparable clinical quality data through which we
      compare quality of primary medical care for coronary heart disease (CHD), stroke,
      hypertension and diabetes across the four UK countries. METHODS: A cross
      sectional analysis was undertaken involving 10,064 general practices in England,
      Scotland, Wales and Northern Ireland. The main outcome measures were prevalence
      rates for CHD, stroke, hypertension and diabetes. Achievement on 14 simple
      process, 3 complex process, 9 intermediate outcome and 5 treatment indicators for
      the four clinical areas. RESULTS: Prevalence varies by up to 28% between the four
      UK countries, which is not reflected in resource distribution between countries,
      and penalises practices in the high prevalence countries (Wales and Scotland).
      Differences in simple process measures across countries are small. Larger
      differences are found for complex process, intermediate outcome and treatment
      measures, most notably for Wales, which has consistently lower quality of care.
      Scotland has generally higher quality than England and Northern Ireland is most
      consistently the highest quality. CONCLUSION: Previously identified weaknesses in
      Wales related to waiting times appear to reflect a more general quality problem
      within NHS Wales. Identifying explanations for the observed differences is
      limited by the lack of comparable data on practice resources and organisation.
      Maximising the value of cross-jurisdictional comparisons of the ongoing natural
      experiment of health policy divergence within the UK requires more detailed
      examination of resource and organisational differences.

PMID- 17535430
TI  - How to optimise the coverage rate of infant and adult immunisations in Europe.
AB  - BACKGROUND: Although vaccination has been proved to be a safe, efficacious, and
      cost-effective intervention, immunisation rates remain suboptimal in many
      European countries, resulting in poor control of many vaccine-preventable
      diseases. DISCUSSION: The Summit of Independent European Vaccination Experts
      focused on the perception of vaccines and vaccination by the general public and
      healthcare professionals and discussed ways to improve vaccine uptake in Europe.
      Despite the substantial impact and importance of the media, healthcare
      professionals were identified as the main advocates for vaccination and the most
      important source of information about vaccines for the general public. Healthcare
      professionals should receive more support for their own education on vaccinology,
      have rapid access to up-to-date information on vaccines, and have easy access to
      consultation with experts regarding vaccination-related problems. Vaccine
      information systems should be set up to facilitate promotion of vaccination.
      SUMMARY: Every opportunity to administer vaccines should be used, and active
      reminder systems should be set up. A European vaccine awareness week should be
      established.

PMID- 17535431
TI  - ConiferEST: an integrated bioinformatics system for data reprocessing and mining
      of conifer expressed sequence tags (ESTs).
AB  - BACKGROUND: With the advent of low-cost, high-throughput sequencing, the amount
      of public domain Expressed Sequence Tag (EST) sequence data available for both
      model and non-model organism is growing exponentially. While these data are
      widely used for characterizing various genomes, they also present a serious
      challenge for data quality control and validation due to their inherent
      deficiencies, particularly for species without genome sequences. DESCRIPTION:
      ConiferEST is an integrated system for data reprocessing, visualization and
      mining of conifer ESTs. In its current release, Build 1.0, it houses 172,229
      loblolly pine EST sequence reads, which were obtained from reprocessing raw DNA
      sequencer traces using our software--WebTraceMiner. The trace files were
      downloaded from NCBI Trace Archive. ConiferEST provides biologists unique, easy
      to-use data visualization and mining tools for a variety of putative sequence
      features including cloning vector segments, adapter sequences, restriction
      endonuclease recognition sites, polyA and polyT runs, and their corresponding
      Phred quality values. Based on these putative features, verified sequence
      features such as 3' and/or 5' termini of cDNA inserts in either sense or non
      sense strand have been identified in-silico. Interestingly, only 30.03% of the
      designated 3' ESTs were found to have an authenticated 5' terminus in the non
      sense strand (i.e., polyT tails), while fewer than 5.34% of the designated 5'
      ESTs had a verified 5' terminus in the sense strand. Such previously ignored
      features provide valuable insight for data quality control and validation of
      error-prone ESTs, as well as the ability to identify novel functional motifs
      embedded in large EST datasets. We found that "double-termini adapters" were
      effective indicators of potential EST chimeras. For all sequences with in-silico
      verified termini/terminus, we used InterProScan to assign protein domain
      signatures, results of which are available for in-depth exploration using our
      biologist-friendly web interfaces. CONCLUSION: ConiferEST represents a unique and
      complementary public resource for EST data integration and mining in conifers by
      reprocessing raw DNA traces, identifying putative sequence features and
      determining and annotating in-silico verified features. Seamlessly integrated
      with other public resources, ConiferEST provides biologists powerful tools to
      verify data, visualize abnormalities, including EST chimeras, and explore large
      EST datasets.

PMID- 17535432
TI  - Contributions of nitrogen deposition and forest regrowth to terrestrial carbon
      uptake.
AB  - BACKGROUND: The amount of reactive nitrogen deposited on land has doubled
      globally and become at least five-times higher in Europe, Eastern United States,
      and South East Asia since 1860 mostly because of increases in fertilizer
      production and fossil fuel burning. Because vegetation growth in the Northern
      Hemisphere is typically nitrogen-limited, increased nitrogen deposition could
      have an attenuating effect on rising atmospheric CO2 by stimulating the
      vegetation productivity and accumulation of carbon in biomass. RESULTS: This
      study shows that elevated nitrogen deposition would not significantly enhance
      land carbon uptake unless we consider its effects on re-growing forests. Our
      results suggest that nitrogen enriched land ecosystems sequestered 0.62-2.33 PgC
      in the 1980s and 0.75-2.21 PgC in the 1990s depending on the proportion and age
      of re-growing forests. During these two decades land ecosystems are estimated to
      have absorbed 13-41% of carbon emitted by fossil fuel burning. CONCLUSION:
      Although land ecosystems and especially forests with lifted nitrogen limitations
      have the potential to decelerate the rise of CO2 concentrations in the
      atmosphere, the effect is only significant over a limited period of time. The
      carbon uptake associated with forest re-growth and amplified by high nitrogen
      deposition will decrease as soon as the forests reach maturity. Therefore,
      assessments relying on carbon stored on land from enhanced atmospheric nitrogen
      deposition to balance fossil fuel emissions may be inaccurate.

PMID- 17535433
TI  - Low E2F1 transcript levels are a strong determinant of favorable breast cancer
      outcome.
AB  - INTRODUCTION: We investigated whether mRNA levels of E2F1, a key transcription
      factor involved in proliferation, differentiation and apoptosis, could be used as
      a surrogate marker for the determination of breast cancer outcome. METHODS: E2F1
      and other proliferation markers were measured by quantitative RT-PCR in 317
      primary breast cancer patients from the Stiftung Tumorbank Basel. Correlations to
      one another as well as to the estrogen receptor and ERBB2 status and clinical
      outcome were investigated. Results were validated and further compared with
      expression-based prognostic profiles using The Netherlands Cancer Institute
      microarray data set reported by Fan and colleagues. RESULTS: E2F1 mRNA expression
      levels correlated strongly with the expression of other proliferation markers,
      and low values were mainly found in estrogen receptor-positive and ERBB2-negative
      phenotypes. Patients with low E2F1-expressing tumors were associated with
      favorable outcome (hazard ratio = 4.3 (95% confidence interval = 1.8-9.9), P =
      0.001). These results were consistent in univariate and multivariate Cox
      analyses, and were successfully validated in The Netherlands Cancer Institute
      data set. Furthermore, E2F1 expression levels correlated well with the 70-gene
      signature displaying the ability of selecting a common subset of patients at good
      prognosis. Breast cancer patients' outcome was comparably predictable by E2F1
      levels, by the 70-gene signature, by the intrinsic subtype gene classification,
      by the wound response signature and by the recurrence score. CONCLUSION:
      Assessment of E2F1 at the mRNA level in primary breast cancer is a strong
      determinant of breast cancer patient outcome. E2F1 expression identified patients
      at low risk of metastasis irrespective of the estrogen receptor and ERBB2 status,
      and demonstrated similar prognostic performance to different gene expression
      based predictors.

PMID- 17535434
TI  - DNA-based watermarks using the DNA-Crypt algorithm.
AB  - BACKGROUND: The aim of this paper is to demonstrate the application of watermarks
      based on DNA sequences to identify the unauthorized use of genetically modified
      organisms (GMOs) protected by patents. Predicted mutations in the genome can be
      corrected by the DNA-Crypt program leaving the encrypted information intact.
      Existing DNA cryptographic and steganographic algorithms use synthetic DNA
      sequences to store binary information however, although these sequences can be
      used for authentication, they may change the target DNA sequence when introduced
      into living organisms. RESULTS: The DNA-Crypt algorithm and image steganography
      are based on the same watermark-hiding principle, namely using the least
      significant base in case of DNA-Crypt and the least significant bit in case of
      the image steganography. It can be combined with binary encryption algorithms
      like AES, RSA or Blowfish. DNA-Crypt is able to correct mutations in the target
      DNA with several mutation correction codes such as the Hamming-code or the WDH
      code. Mutations which can occur infrequently may destroy the encrypted
      information, however an integrated fuzzy controller decides on a set of
      heuristics based on three input dimensions, and recommends whether or not to use
      a correction code. These three input dimensions are the length of the sequence,
      the individual mutation rate and the stability over time, which is represented by
      the number of generations. In silico experiments using the Ypt7 in Saccharomyces
      cerevisiae shows that the DNA watermarks produced by DNA-Crypt do not alter the
      translation of mRNA into protein. CONCLUSION: The program is able to store
      watermarks in living organisms and can maintain the original information by
      correcting mutations itself. Pairwise or multiple sequence alignments show that
      DNA-Crypt produces few mismatches between the sequences similar to all
      steganographic algorithms.

PMID- 17535435
TI  - Absence of dopaminergic neuronal degeneration and oxidative damage in aged DJ-1
      deficient mice.
AB  - Parkinson's disease is the most common movement disorder characterized by
      dopaminergic dysfunction and degeneration. Loss-of-function mutations in the DJ-1
      gene have been linked to autosomal recessive forms of early-onset familial
      Parkinson's disease. DJ-1 is thought to play roles in protection of cells against
      oxidative stress and in maintenance of the normal dopaminergic function in the
      nigrostriatal pathway. Here we investigate the consequence of both DJ-1
      inactivation and aging in mice. We found that DJ-1-/- mice at the age of 24-27
      months have normal numbers of dopaminergic neurons in the substantia nigra and
      normal levels of dopamine and its major metabolites in the striatum. The number
      of noradrenergic neurons in the locus coeruleus is also unchanged in DJ-1-/-
      mice. Moreover, there is no accumulation of oxidative damage or inclusion bodies
      in aged DJ-1-/- brains. Together, these results indicate that loss of DJ-1
      function alone is insufficient to cause nigral degeneration and oxidative damage
      in the life span of mice.

PMID- 17535436
TI  - Valuing the scholarship of integration and the scholarship of application in the
      academy for health sciences scholars: recommended methods.
AB  - In the landmark 1990 publication Scholarship Reconsidered, Boyer challenged the
      'teaching verses research debates' by advocating for the scholarship of
      discovery, teaching, integration, and application. The scholarship of discovery
      considers publications and research as the yardstick in the merit, promotion and
      tenure system the world over. But this narrow view of scholarship does not fully
      support the obligations of universities to serve global societies and to improve
      health and health equity. Mechanisms to report the scholarship of teaching have
      been developed and adopted by some universities. In this article, we contribute
      to the less developed areas of scholarship, i.e. integration and application. We
      firstly situate the scholarship of discovery, teaching, integration and
      application within the interprofessional and knowledge exchange debates. Second,
      we propose a means for health science scholars to report the process and outcomes
      of the scholarship of integration and application with other disciplines,
      decision-makers and communities. We conclude with recommendations for structural
      and process change in faculty merit, tenure, and promotion systems so that health
      science scholars with varied academic portfolios are valued and many forms of
      academic scholarship are sustained. It is vital academic institutions remain
      relevant in an era when the production of knowledge is increasingly recognized as
      a social collaborative activity.

PMID- 17535437
TI  - Common genomic features of Campylobacter jejuni subsp. doylei strains distinguish
      them from C. jejuni subsp. jejuni.
AB  - BACKGROUND: Campylobacter jejuni has been divided into two subspecies: C. jejuni
      subsp. jejuni (Cjj) and C. jejuni subsp. doylei (Cjd). Nearly all of the C.
      jejuni strains isolated are Cjj; nevertheless, although Cjd strains are isolated
      infrequently, they differ from Cjj in two key aspects: they are obtained
      primarily from human clinical samples and are associated often with bacteremia,
      in addition to gastroenteritis. In this study, we utilized multilocus sequence
      typing (MLST) and a DNA microarray-based comparative genomic indexing (CGI)
      approach to examine the genomic diversity and gene content of Cjd strains.
      RESULTS: A geographically diverse collection of eight Cjd strains was examined by
      MLST and determined to be phylogenetically distinct from Cjj strains. Microarray
      based CGI approach also supported this. We were able to demonstrate that Cjd
      strains exhibited divergence from Cjj strains NCTC 11168 and RM1221 in many of
      the intraspecies hypervariable regions. Moreover, multiple metabolic, transport
      and virulence functions (e.g. cytolethal distending toxin) were shown to be
      absent in the Cjd strains examined. CONCLUSION: Our data demonstrate that Cjd are
      phylogenetically distinct from Cjj strains. Using the CGI approach, we identified
      subsets of absent genes from amongst the C. jejuni genes that provide clues as to
      the potential evolutionary origin and unusual pathogenicity of Cjd.

PMID- 17535438
TI  - Unequal evolutionary conservation of human protein interactions in interologous
      networks.
AB  - BACKGROUND: Protein-protein interaction (PPI) networks have been transferred
      between organisms using interologs, allowing model organisms to supplement the
      interactomes of higher eukaryotes. However, the conservation of various network
      components has not been fully explored. Unequal conservation of certain network
      components may limit the ability to fully expand the target interactomes using
      interologs. RESULTS: In this study, we transfer high quality human interactions
      to lower eukaryotes, and examine the evolutionary conservation of individual
      network components. When human proteins are mapped to yeast, we find a strong
      positive correlation (r = 0.50, P = 3.9 x 10(-4)) between evolutionary
      conservation and the number of interacting proteins, which is also found when
      mapped to other model organisms. Examining overlapping PPI networks, Gene
      Ontology (GO) terms, and gene expression data, we are able to demonstrate that
      protein complexes are conserved preferentially, compared to transient
      interactions in the network. Despite the preferential conservation of complexes,
      and the fact that the human interactome comprises an abundance of transient
      interactions, we demonstrate how transferring human PPIs to yeast augments this
      well-studied protein interaction network, using the coatomer complex and
      replisome as examples. CONCLUSION: Human proteins, like yeast proteins, show a
      correlation between the number of interacting partners and evolutionary
      conservation. The preferential conservation of proteins with higher degree leads
      to enrichment in protein complexes when interactions are transferred between
      organisms using interologs.

PMID- 17535439
TI  - Near-infrared (NIR) spectroscopy. A new method for arthroscopic evaluation of low
      grade degenerated cartilage lesions. Results of a pilot study.
AB  - BACKGROUND: Arthroscopy is a highly sensitive method of evaluating high-grade
      cartilage lesions but the detection of low-grade lesions is often is unreliable.
      Objective measurements are required. A novel NIRS (near-infrared-spectroscopy)
      device for detection of low-grade cartilage defects was evaluated in a
      preliminary clinical study. METHODS: In 12 patients who had undergone
      arthroscopy, the cartilage lesions within the medial knee compartment were
      classified according to the ICRS protocol. With a NIR spectrometer system and an
      optical probe, similar in design to a hook used for routine arthroscopy, the
      optical properties of cartilage were measured during arthroscopy. RESULTS: The
      mean ratio of 2 NIR absorption bands of intact cartilage 3.8 (range 2.3 to
      8.7).was significantly lower than that of cartilage with grade 1 lesions (12.8,
      range 4.8 to 19.6) and grade 2 lesions (13.4, range 10.4 to 15.4).No differences
      were observed between grade 1 and grade 2 lesions. CONCLUSION: NIRS can be used
      to distinguish between ICRS grade 1 lesions and healthy cartilage during
      arthroscopic surgeries. The results of this clinical study demonstrate the
      potential of NIRS to objectify classical arthroscopic grading systems.

PMID- 17535440
TI  - Population mortality during the outbreak of Severe Acute Respiratory Syndrome in
      Toronto.
AB  - BACKGROUND: Extraordinary infection control measures limited access to medical
      care in the Greater Toronto Area during the 2003 Severe Acute Respiratory
      Syndrome (SARS) outbreak. The objective of this study was to determine if the
      period of these infection control measures was associated with changes in overall
      population mortality due to causes other than SARS. METHODS: Observational study
      of death registry data, using Poisson regression and interrupted time-series
      analysis to examine all-cause mortality rates (excluding deaths due to SARS)
      before, during, and after the SARS outbreak. The population of Ontario was
      grouped into the Greater Toronto Area (N = 2.9 million) and the rest of Ontario
      (N = 9.3 million) based upon the level of restrictions on delivery of clinical
      services during the SARS outbreak. RESULTS: There was no significant change in
      mortality in the Greater Toronto Area before, during, and after the period of the
      SARS outbreak in 2003 compared to the corresponding time periods in 2002 and
      2001. The rate ratio for all-cause mortality during the SARS outbreak was 0.99
      [95% Confidence Interval (CI) 0.93-1.06] compared to 2002 and 0.96 [95% CI 0.90
      1.03] compared to 2001. An interrupted time series analysis found no significant
      change in mortality rates in the Greater Toronto Area associated with the period
      of the SARS outbreak. CONCLUSION: Limitations on access to medical services
      during the 2003 SARS outbreak in Toronto had no observable impact on short-term
      population mortality. Effects on morbidity and long-term mortality were not
      assessed. Efforts to contain future infectious disease outbreaks due to influenza
      or other agents must consider effects on access to essential health care
      services.

PMID- 17535442
TI  - Supplement use in sport: is there a potentially dangerous incongruence between
      rationale and practice?
AB  - BACKGROUND: Supplement use by athletes is complex and research supports the
      alarming notion of misinformed decisions regarding supplements. HYPOTHESIS: A
      frequent divergence between the type of supplements chosen by athletes and the
      rationale dictating the supplement use is hypothesized. Thus, a potentially
      dangerous incongruence may exist between rationale and practice. TESTING THE
      HYPOTHESIS: In the continued absence of reliable data on supplement use, an
      alternative approach of studying the reasons underlying supplement use in
      athletes is proposed to determine whether there is an incongruence between
      rationale and practice. Existing data from large scale national surveys can be
      used to investigate this incongruence. IMPLICATIONS OF THE HYPOTHESIS: In this
      report, analyses of distinctive patterns between the use and rationale for use of
      supplements among athletes are recommended to explore this potentially dangerous
      phenomenon.

PMID- 17535441
TI  - Case control study of the geographic variability of exposure to disinfectant
      byproducts and risk for rectal cancer.
AB  - BACKGROUND: Levels of byproducts that result from the disinfection of drinking
      water vary within a water distribution system. This prompted us to question
      whether the risk for rectal cancer also varies, depending upon one's long term
      geographic location within the system. Such a geographic distribution in rectal
      cancer risk would follow naturally from an association between level of byproduct
      and rectal cancer risk. We assess the effects of estimated geographic variability
      in exposure to some of the components of the trihalomethane group of disinfectant
      byproducts (DBPs) on the odds ratios and probabilities for rectal cancer in white
      males in a case control study of 128 cases and 253 controls, conducted in Monroe
      County, Western New York State, U.S.A. The study was designed around health data
      initially collected at the University at Buffalo (Department of Social and
      Preventative Medicine) as part of the Upstate New York Diet Study, and
      trihalomethane (THM) data collected from a separate independent study of THMs
      conducted by Monroe County Department of Health. Case participants were chosen
      from hospital pathology records. The controls are disease-free white males
      between 35-90 years old, living in Monroe County, and chosen from control groups
      for studies from cancer of five other (unrelated) sites. Using a combination of
      case control methodology and spatial analysis, the spatial patterns of THMs and
      individual measures of tap water consumption provide estimates of the effects of
      ingestion of specific amounts of some DBPs on rectal cancer risk. Trihalomethane
      (THM) data were used to spatially interpolate levels at the taps of cases and
      controls, and odds ratios were estimated using logistic regression to assess the
      effects of estimated THM exposure dose on cancer risk, adjusting for alcohol,
      dietary beta carotene intake, tap water intake, and total caloric intake.
      RESULTS: Trihalomethane levels varied spatially within the county; although risk
      for rectal cancer did not increase with total level of trihalomethanes,
      increasing levels of the component bromoform (measured in ug/day) did correspond
      with an increase in odds ratios (OR = 1.85; 95% CI = 1.25 - 2.74) for rectal
      cancer. The highest quartiles of estimated consumption of bromoform (1.69-15.43
      ug/day) led to increased risk for rectal cancer (OR = 2.32; 95% CI = 1.22-4.39).
      Two other THMs were marginally associated with an increase in risk -
      chlorodibromomethane (OR = 1.78, 95% CI = 1.00-3.19) and bromodichloromethane (OR
      = 1.15; 95% CI = 1.00-1.32). CONCLUSION: Levels of THMs in the water distribution
      system exhibited spatial variation that was partially due to variation in water
      age. We also observed a geographic pattern of increased risk of rectal cancer in
      areas with the highest levels of bromoform in the county.

PMID- 17535443
TI  - PCR-based landmark unique gene (PLUG) markers effectively assign homoeologous
      wheat genes to A, B and D genomes.
AB  - BACKGROUND: EST-PCR markers normally represent specific products from target
      genes, and are therefore effective tools for genetic analysis. However, because
      wheat is an allohexaploid plant, PCR products derived from homoeologous genes are
      often simultaneously amplified. Such products may be easier to differentiate if
      they include intron sequences, which are more polymorphic than exon sequences.
      However, genomic sequence data for wheat are limited; therefore it is difficult
      to predict the location of introns. By using the similarities in gene structures
      between rice and wheat, we developed a system called PLUG (PCR-based Landmark
      Unique Gene) to design primers so that PCR products include intron sequences. We
      then investigated whether products amplified using such primers could serve as
      markers able to distinguish multiple products derived from homoeologous genes.
      RESULTS: The PLUG system consists of the following steps: (1) Single-copy rice
      genes (Landmark Unique Gene loci; LUGs) exhibiting high degrees of homology to
      wheat UniGene sequences are extracted; (2) Alignment analysis is carried out
      using the LUGs and wheat UniGene sequences to predict exon-exon junctions, and
      LUGs which can be used to design wheat primers flanking introns (TaEST-LUGs) are
      extracted; and (3) Primers are designed in an interactive manner. From a total of
      4,312 TaEST-LUGs, 24 loci were randomly selected and used to design primers. With
      all of these primer sets, we obtained specific, intron-containing products from
      the target genes. These markers were assigned to chromosomes using wheat
      nullisomic-tetrasomic lines. By PCR-RFLP analysis using agarose gel
      electrophoresis, 19 of the 24 markers were located on at least one chromosome.
      CONCLUSION: In the development of wheat EST-PCR markers capable of efficiently
      sorting products derived from homoeologous genes, it is important to design
      primers able to amplify products that include intron sequences with
      insertion/deletion polymorphisms. Using the PLUG system, wheat EST sequences that
      can be used for marker development are selected based on comparative genomics
      with rice, and then primer sets flanking intron sequences are prepared in an
      interactive, semi-automatic manner. Hence, the PLUG system is an effective tool
      for large-scale marker development.

PMID- 17535444
TI  - The different roles of cyclinD1-CDK4 in STP and mGluR-LTD during the postnatal
      development in mice hippocampus area CA1.
AB  - BACKGROUND: Cell-cycle-related proteins, such as cyclins or cyclin-dependent
      kinases, may have functions beyond that of cell cycle regulation. The expression
      and translocation of cyclinD1-CDK4 in post-mitotic neurons indicate that they may
      have supplementary functions in differentiated neurons that might be associated
      with neuronal plasticity. RESULTS: In the present study, our findings showed that
      the expression of CDK4 was localized mostly in nuclei and cytoplasm of pyramidal
      cells of CA1 at postnatal day 10 (P10); whereas at P28 staining of CDK4 could be
      detected predominantly in the cytoplasm but not nuclei. Basal synaptic
      transmission was normal in the presence of CDK4 inhibitor. Short-term synaptic
      plasticity (STP) was impaired in CDK4 inhibitor pre-treated slices both from
      neonatal (P8-15) and adolescent (P21-35) animals; however there was no
      significant change in paired-pulse facilitation (PPF) in slices pre-incubated
      with the CDK4 inhibitor from adolescent animals. By the treatment of CDK4
      inhibitor, the induction or the maintenance of Long-term potentiation (LTP) in
      response to a strong tetanus and NMDA receptor-dependent long-term depression
      (LTD) were normal in hippocampus. However, long-term depression (LTD) induced
      either by group I metabotropic glutamate receptors (mGluRs) agonist or by paired
      pulse low-frequency stimulation (PP-LFS) was impaired in CDK4 inhibitor
      pretreated slices both from neonatal and adolescent animals. But the effects of
      the CDK4 inhibitor at slices from adolescent animals were not as robust as at
      slices from neonatal animals. CONCLUSION: Our results indicated that the
      activation of cyclinD1-CDK4 is required for short-term synaptic plasticity and
      mGluR-dependent LTD, and suggested that this cyclin-dependent kinase may have
      different roles during the postnatal development in mice hippocampus area CA1.

PMID- 17535445
TI  - bZIPDB: a database of regulatory information for human bZIP transcription
      factors.
AB  - BACKGROUND: Basic region-leucine zipper (bZIP) proteins are a class of
      transcription factors (TFs) that play diverse roles in eukaryotes. Malfunctions
      in these proteins lead to cancer and various other diseases. For detailed
      characterization of these TFs, further public resources are required.
      DESCRIPTION: We constructed a database, designated bZIPDB, containing information
      on 49 human bZIP TFs, by means of automated literature collection and manual
      curation. bZIPDB aims to provide public data required for deciphering the gene
      regulatory network of the human bZIP family, e.g., evaluation or reference
      information for the identification of regulatory modules. The resources provided
      by bZIPDB include (1) protein interaction data including direct binding,
      phosphorylation and functional associations between bZIP TFs and other cellular
      proteins, along with other types of interactions, (2) bZIP TF-target gene
      relationships, (3) the cellular network of bZIP TFs in particular cell lines, and
      (4) gene information and ontology. In the current version of the database, 721
      protein interactions and 560 TF-target gene relationships are recorded. bZIPDB is
      annually updated for the newly discovered information. CONCLUSION: bZIPDB is a
      repository of detailed regulatory information for human bZIP TFs that is
      collected and processed from the literature, designed to facilitate analysis of
      this protein family. bZIPDB is available for public use at
      http://biosoft.kaist.ac.kr/bzipdb.

PMID- 17535446
TI  - GOGOT: a method for the identification of differentially expressed fragments from
      cDNA-AFLP data.
AB  - BACKGROUND: One-dimensional (1-D) electrophoretic data obtained using the cDNA
      AFLP method have attracted great interest for the identification of
      differentially expressed transcript-derived fragments (TDFs). However, high
      throughput analysis of the cDNA-AFLP data is currently limited by the need for
      labor-intensive visual evaluation of multiple electropherograms. We would like to
      have high-throughput ways of identifying such TDFs. RESULTS: We describe a
      method, GOGOT, which automatically detects the differentially expressed TDFs in a
      set of time-course electropherograms. Analysis by GOGOT is conducted as follows:
      correction of fragment lengths of TDFs, alignment of identical TDFs across
      different electropherograms, normalization of peak heights, and identification of
      differentially expressed TDFs using a special statistic. The output of the
      analysis is a highly reduced list of differentially expressed TDFs. Visual
      evaluation confirmed that the peak alignment was performed perfectly for the TDFs
      by virtue of the correction of peak fragment lengths before alignment in step 1.
      The validity of the automated ranking of TDFs by the special statistic was
      confirmed by the visual evaluation of a third party. CONCLUSION: GOGOT is useful
      for the automated detection of differentially expressed TDFs from cDNA-AFLP
      temporal electrophoretic data. The current algorithm may be applied to other
      electrophoretic data and temporal microarray data.

PMID- 17535447
TI  - Simulating the carbon balance of a temperate larch forest under various
      meteorological conditions.
AB  - BACKGROUND: Changes in the timing of phenological events may cause the annual
      carbon budget of deciduous forests to change. Therefore, one should take such
      events into account when evaluating the effects of global warming on deciduous
      forests. In this article, we report on the results of numerical experiments done
      with a model that includes a phenological module simulating the timing of bud
      burst and other phenological events and estimating maximum leaf area index.
      RESULTS: This study suggests that the negative effects of warming on tree
      productivity (net primary production) outweigh the positive effects of a
      prolonged growing season. An increase in air temperature by 3 degrees C (5
      degrees C) reduces cumulative net primary production by 21.3% (34.2%). Similarly,
      cumulative net ecosystem production (the difference between cumulative net
      primary production and heterotrophic respiration) decreases by 43.5% (64.5%) when
      temperatures are increased by 3 degrees C (5 degrees C). However, the positive
      effects of CO2 enrichment (2 x CO2) outweigh the negative effects of warming (<5
      degrees C). CONCLUSION: Although the model was calibrated and validated for a
      specific forest ecosystem, the implications of the study may be extrapolated to
      deciduous forests in cool-temperate zones. These forests share common features,
      and it can be conjectured that carbon stocks would increase in such forests in
      the face of doubled CO2 and increased temperatures as long as the increase in
      temperature does not exceed 5 degrees C.

PMID- 17535449
TI  - The construction of self in online support groups for victims of domestic
      violence.
AB  - In this article, we use the exemplar of domestic violence to examine the
      construction of self online. To do this, a positional approach to language is
      combined with a Bakhtinian inspired, phenomenological approach to language. Such
      an approach is designed to capture both the rhetorical and the intoned quality of
      language. This approach also draws attention to the role of the assumed community
      in dialogically interrupting and reflexively structuring the construction of self
      online. From this conceptual perspective, we examine a variety of posted messages
      to the public bulletin boards of a number of different online support groups for
      domestic violence. Three interpenetrating analytic themes emerged from this
      analysis: (1) The construction of self in relation to online support group
      members; (2) The construction of self in relation to abuser and (3) The
      construction of self in relation to past self. These themes are explicated over
      four key extracts. These extracts are also analysed in terms of the insights they
      offer into the phenomenological, positional and dialogical dimensions of an
      utterance directed at a community.

PMID- 17535450
TI  - The ME Bandwagon and other labels: constructing the genuine case in talk about a
      controversial illness.
AB  - This paper examines the discourse of morality surrounding 'ME' as a contested
      illness, looking at how GPs and ME group members differentiate between the
      category of 'genuine ME sufferer' and the 'bandwagon'. 'Jumping on the bandwagon'
      is a metaphor commonly used to describe the activity of 'following the crowd' in
      order to gain an advantage. This discursive analysis shows how 'bandwagon'
      categories are constructed in contrast to the category of genuine sufferer.
      People who jump on the bandwagon are accused of matching their symptoms to media
      stereotypes, adopting trendy illnesses ('fads'), or using 'tickets' to avoid
      facing up to psychological illnesses. Both GPs and ME group members construct a
      differential moral ordering of physical and psychological illness categories,
      where the latter assumes a lesser status. The paper concludes that against a
      background of medical uncertainty and controversy, the 'bandwagon' and other
      derogatory labels function as contrast categories that work to establish the
      existence of 'ME' as a genuine illness.

PMID- 17535448
TI  - Regulation of p73 by Hck through kinase-dependent and independent mechanisms.
AB  - BACKGROUND: p73, a p53 family member is a transcription factor that plays a role
      in cell cycle, differentiation and apoptosis. p73 is regulated through post
      translational modifications and protein interactions. c-Abl is the only known
      tyrosine kinase that phosphorylates and activates p73. Here we have analyzed the
      role of Src family kinases, which are involved in diverse signaling pathways, in
      regulating p73. RESULTS: Exogenously expressed as well as cellular Hck and p73
      interact in vivo. In vitro binding assays show that SH3 domain of Hck interacts
      with p73. Co-expression of p73 with Hck or c-Src in mammalian cells resulted in
      tyrosine phosphorylation of p73. Using site directed mutational analysis, we
      determined that Tyr-28 was the major site of phosphorylation by Hck and c-Src,
      unlike c-Abl which phosphorylates Tyr-99. In a kinase dependent manner, Hck co
      expression resulted in stabilization of p73 protein in the cytoplasm. Activation
      of Hck in HL-60 cells resulted in tyrosine phosphorylation of endogenous p73.
      Both exogenous and endogenous Hck localize to the nuclear as well as cytoplasmic
      compartment, just as does p73. Ectopically expressed Hck repressed the
      transcriptional activity of p73 as determined by promoter assays and semi
      quantitative RT-PCR analysis of the p73 target, Ipaf and MDM2. SH3 domain-
      dependent function of Hck was required for its effect on p73 activity, which was
      also reflected in its ability to inhibit p73-mediated apoptosis. We also show
      that Hck interacts with Yes associated protein (YAP), a transcriptional co
      activator of p73, and shRNA mediated knockdown of YAP protein reduces p73 induced
      Ipaf promoter activation. CONCLUSION: We have identified p73 as a novel substrate
      and interacting partner of Hck and show that it regulates p73 through mechanisms
      that are dependent on either catalytic activity or protein interaction domains.
      Hck-SH3 domain-mediated interactions play an important role in the inhibition of
      p73-dependent transcriptional activation of a target gene, Ipaf, as well as
      apoptosis.

PMID- 17535451
TI  - The addition of anticipated regret to attitudinally based, goal-directed models
      of information search behaviours under conditions of uncertainty and risk.
AB  - Social science attempts to incorporate emotions into models of judgment and
      decision making have faced significant theoretical challenges, as well as
      produced conflicting empirical results. The following study first contributes to
      the body of knowledge by providing a theoretical explanation for the observed
      conflicting results from such models. In fact, both extant theory and the results
      reported herein suggest that a certain amount of variability in results should be
      expected from empirical investigations based on such models, particularly related
      to differences in respondents' level of affective versus cognitive involvement.
      Second, an argument is presented for considering a special case of Perugini and
      Bagozzi's (2001) Model of Goal-directed Behaviours (MGBs) when investigating
      these issues using attitude-based explanations of goal-related behaviours.
      Specifically, empirical evidence is presented for broadening the MGB model by
      including anticipated regret as an explanatory variable independent of other
      anticipated emotions, and deepening the theory by calling for multidimensional
      conceptualizations of the attitude and perceived behavioural control constructs.
      The implications of the reported study are presented and discussed.

PMID- 17535452
TI  - Dilemmatic human-animal boundaries in Britain and Romania: post-materialist and
      materialist dehumanization.
AB  - Theories of dehumanization generally assume a single clear-cut, value-free and
      non-dilemmatic boundary between the categories 'human' and 'animal'. The present
      study highlights the relevance of dilemmas involved in drawing that boundary. In
      six focus groups carried out in Romania and Britain, 42 participants were
      challenged to think about dilemmas pertaining to animal and human life. Four
      themes were identified: rational autonomy, sentience, speciesism and maintaining
      materialist and post-materialist values. Sentience made animals resemble humans,
      while humans' rational autonomy made them distinctive. Speciesism underlay the
      human participants' prioritization of their own interests over those of animals,
      and a conservative consensus that the existing social system could not change
      supported this speciesism when it was challenged. Romanian participants appealed
      to Romania's lack of modernity and British participants to Britain's modernity to
      justify such conservatism. The findings suggest that the human-animal boundary is
      not essentialized; rather it seems that such boundary is constructed in a
      dilemmatic and post hoc way. Implications for theories of dehumanization are
      discussed.

PMID- 17535453
TI  - Common patterns of sense making: a discursive reading of quantitative and
      interpretative data on sexual boredom.
AB  - This paper explores the notion of sexual boredom through combining the use of
      qualitative and quantitative methods. Drawing on ideas from discursive
      psychology, we provide an interpretative reading of both numerical and textual
      data obtained via a postal questionnaire. Within the mixed-methods strategy
      adopted here, the questionnaire is treated as a medium that can deliver
      interesting material about prevalent linguistic resources, their content and
      pattern of use, available to romantic partners in making sense of sexual boredom.
      A total of 144 women and 66 men from the general population completed a set of
      structured questions, including a Sexual Boredom Scale (SBS; Watt & Ewing, 1996),
      followed by an open-ended question prompting more elaborated views on the topic.
      Statistical analysis found gender to explain some of the variation across SBS
      scores. An interpretative analysis of respondent ratings of
      disagreement/agreement and the actual meaning content of the scale's statements
      also reveals ranked and gendered regularities. Written responses to the open
      ended question were subjected to a thematic analysis, revealing how specific
      changes to quality of sex, intensity of sexual interest and degree of romantic
      relatedness with a current partner are used by participants to delineate key
      dimensions of sexual boredom. Overall, the unfolding narratives of sexual boredom
      are greatly indebted to a static view of relationship satisfaction founded on
      wishful expectations for consistent, idealized displays of sexual excitement and
      interest from oneself and one's partner. The interplay between these
      understandings and a missing discourse of sexuo-erotic calmness is also
      considered.

PMID- 17535454
TI  - Offending the other: deconstructing narratives of deviance and pathology.
AB  - Narratives of homophobia and the repathologization of gay men now emerge and
      coalesce in often unconsidered ways. Within this paper, we present a
      deconstructive analysis of a recent paper published within the British Journal of
      Social Psychology (Crossley, 2004) and highlight how a narrative of repathology
      emerges through the selective appropriation of particular textual sources. By
      employing pathological constructions of sexual conduct between men; focusing upon
      singular homogenized constructions of gay men and simplistic constructions of
      health promotion and through a process of reconstructing HIV as a gay plague and
      it is possible to embroider a moral tale which constitutes a further deviant
      'othering' of gay men. We contend that by employing (functional) discourses of
      'unconscious motivation', together with a constellation of disclaimers, caveats
      and tokenistic pluralization, it becomes possible for psychologists to engage in
      homophobic knowledge production whilst maintaining an identity as a
      (dis)interested professional. Our analysis raises issues pertinent to all social
      psychologists engaged in 'suspicious' research on 'the other'. To this end, we
      expand our critique by employing ideas from Ricoeur's hermeneutic phenomenology
      to provide more general discussion of ethical and constructive ways of engaging
      in textual analyses of persons outside one's own tradition.

PMID- 17535455
TI  - The rhetoric of acculturation: when integration means assimilation.
AB  - Viewing traditional acculturation literature through a social constructionist
      lens, the present paper identifies a number of limitations with this research. A
      discourse analytic approach to acculturation is offered as a means of addressing
      some of these issues. Drawing on examples taken from British print media debate
      surrounding the issue of faith schooling in the UK, an analysis is presented
      which illustrates the manner in which, though optimally positioned within
      acculturative moral hierarchies directed towards the legitimization of both pro-
      and anti-faith schooling debates, integration rhetoric often conceals the (re
      )production of a more implicit assimilationism. Findings are discussed in terms
      of their implications for hegemonically structured acculturative power relations.
      This exploratory analysis provides the basis for reflection on the benefits of a
      discursive approach to acculturation. Moreover, the dependence of integrationist
      discourse on a series of socio-spatial resources is considered and, following on
      from Dixon and Durrheim's (2000) discursive re-conceptualization of place
      identity, is taken to signify the need for a more environmentally 'grounded'
      approach to acculturation.

PMID- 17535456
TI  - Ideologies of moral exclusion: a critical discursive reframing of
      depersonalization, delegitimization and dehumanization.
AB  - This paper focuses on some of the issues that arise when one treats notions such
      as depersonalization, delegitimization and dehumanization as social practices. It
      emphasizes the importance of: (a) understanding depersonalizing, delegitimizing
      and dehumanizing constructions as embedded in descriptions of located spatial
      activities and moral standings in the world and (b) invoking and building a socio
      moral order linked to notions of lesser humanity or non-humanity, (spatial)
      transgression and abjection. These concerns are illustrated by taking talk on
      Romanies as a case in point from interviews with Romanian middle-class
      professionals. It is argued that a focus on description rather than explanation
      might be more effective in understanding the dynamics of ideologies of moral
      exclusion.

PMID- 17535457
TI  - In the ruins of representation: identity, individuality, subjectification.
AB  - This paper explores a threefold shift in our understanding of identity formation
      and self-relationality: from an essentialist understanding of identity, to
      discursive and constructivist approaches, to, finally, the notion of embodied
      subjectification. The main target of this paper is to historicize these ideas and
      to localize them in the current social and political conditions of North-Atlantic
      societies. The core argument is that these three steps in reformulating the
      concept of identity correspond to an emerging form of subjectivity, affirmative
      subjectivity, which is bound to the proliferation of the post-Fordist
      reorganization of the social and political realm. The three theoretical shifts
      and their social situatedness will be illustrated through a rereading of some
      ideas from Lev S. Vygotsky's late theory, Michel Foucault's account of government
      and Jacques Ranciere's political philosophy.

PMID- 17535458
TI  - The importance of social identity content in a setting of chronic social
      conflict: understanding intergroup relations in Northern Ireland.
AB  - Two studies (N=117, 112) were conducted with school students in Northern Ireland
      to investigate the neglected relationship between social identity content and
      intergroup relations. Study 1 tested and found support for two hypotheses. The
      first was that the association between in-group identification and negative
      behavioural intentions would be moderated by antagonistic identity content. The
      second was that the antagonistic identity content mediates the relationship
      between the experience of intergroup antagonism and negative behavioural
      intentions. Study 2 replicated these findings at a time of reduced intergroup
      violence, and supplemented them with a qualitative-quantitative analysis of
      participants' written responses. In addition, findings demonstrate the importance
      of appreciating the content and meaning of social identities when theorizing
      about intergroup relations and developing conflict management interventions.

PMID- 17535459
TI  - In search of the big fish: investigating the coexistence of the big-fish-little
      pond effect with the positive effects of upward comparisons.
AB  - Blanton, Buunk, Gibbons, and Kuyper (1999) and Huguet, Dumas, Monteil, and
      Genestoux (2001) found that children nominated a social comparison target who
      slightly outperformed them in class with a beneficial effect on course grades -
      an assimilation effect, but with no effects on self-evaluation. However, big-fish
      little-pond effect (BFLPE) research has shown that attending a high-ability
      school has a negative effect on academic self-concept--a contrast effect. To
      resolve this apparent conflict, the present investigation (1) tested the BFLPE in
      the Netherlands and France, using nationally representative samples (Study 1) and
      (2) further analysed (using more sophisticated analyses) the Dutch (Blanton et
      al.) study (Study 2) and the French (Huguet et al.) study including new French
      data (Study 3), to examine whether the BFLPE coexisted with, or was moderated by,
      the beneficial impact of upward comparisons. In support of the BFLPE, all studies
      found the negative effects of school- or class-average ability on self
      evaluation, demonstrating that these assimilation and contrast effects can
      coexist.

PMID- 17535460
TI  - Rhetorically self-sufficient arguments in Western Australian parliamentary
      debates on Lesbian and Gay Law Reform.
AB  - Western Australia's Acts Amendment (Lesbian and Gay Law Reform) Bill 2001
      delivered a measure of legal equality in such areas as property transfer,
      superannuation, inheritance and discrimination, and more controversially,
      adoption, lesbian access to IVF, lowering the age of consent for sex between men
      from 21 to 16, and incorporating information on homosexuality into high school
      sex education classes. This paper examines the use of various moral principles
      within parliamentary speeches supporting or opposing the legislation, and the
      extent to which they were treated by members as beyond question, or 'rhetorically
      self-sufficient'. The resources of 'equality', 'human rights', 'democracy', 'the
      interests of the majority' and 'the interests of children' were given a kind of
      beyond-question, self-sufficient status, but their use was able to be undermined
      in a number of ways, relating to members' management of what the Bill was
      'about', and the flexibility of these social constructs. It is argued that rather
      than pitting one set of resources against another, members on both sides of the
      debate faced a rhetorical pressure to adopt and mobilize all of the same self
      sufficient moral resources, due to the flexible, constructed and non
      hierarchical, yet often rhetorically self-sufficient nature of common-sense moral
      principles.

PMID- 17535461
TI  - Integrating social identity theory and the theory of planned behaviour to explain
      decisions to engage in sustainable agricultural practices.
AB  - The present research integrates core aspects of social identity theory with the
      theory of planned behaviour to investigate factors influencing engagement in
      sustainable agricultural practices. Using a two-wave prospective design, two
      studies were conducted with samples of farmers (N = 609 and N = 259,
      respectively). At Time 1, a questionnaire survey assessed theory of planned
      behaviour variables in relation to engaging in riparian zone management (a
      sustainable agricultural practice). In addition, intergroup perceptions (i.e.
      relations between rural and urban groups), group norms and group identification
      were assessed. At Time 2, self-reported behaviour was measured. There was support
      for the integrated model across both studies. As predicted, past behaviour,
      attitudes and perceived behavioural control were significant predictors of
      intentions, and intentions significantly predicted self-reported behaviour. Group
      norms and intergroup perceptions were also significant predictors of intentions
      providing support for the inclusion of social identity concepts in the theory of
      planned behaviour. More supportive group norms were associated with higher
      intentions, especially for high-group identifiers. In contrast, more negative
      intergroup perceptions were associated with lower intentions and, unexpectedly,
      this effect only emerged for low-group identifiers. This suggests that in the
      context of decisions to engage in riparian zone management, an important
      sustainable agricultural practice, high identifiers are influenced predominantly
      by in-group rather than out-group considerations, whereas low identifiers may
      attend to cues from both the in-group and the out-group when making their
      decisions.

PMID- 17535462
TI  - Memory for curvature of objects: haptic touch vs. vision.
AB  - The present study examined the role of vision and haptics in memory for stimulus
      objects that vary along the dimension of curvature. Experiment 1 measured haptic
      haptic (T-T) and haptic-visual (T-V) discrimination of curvature in a short-term
      memory paradigm, using 30-second retention intervals containing five different
      interpolated tasks. Results showed poorest performance when the interpolated
      tasks required spatial processing or movement, thereby suggesting that haptic
      information about shape is encoded in a spatial-motor representation. Experiment
      2 compared visual-visual (V-V) and visual-haptic (V-T) short-term memory, again
      using 30-second delay intervals. The results of the ANOVA failed to show a
      significant effect of intervening activity. Intra-modal visual performance and
      cross-modal performance were similar. Comparing the four modality conditions
      (inter-modal V-T, T-V; intra-modal V-V, T-T, by combining the data of Experiments
      1 and 2), in a global analysis, showed a reliable interaction between intervening
      activity and experiment (modality). Although there appears to be a general
      tendency for spatial and movement activities to exert the most deleterious
      effects overall, the patterns are not identical when the initial stimulus is
      encoded haptically (Experiment 1) and visually (Experiment 2).

PMID- 17535463
TI  - Explaining inappropriate strategy selection in a simple reasoning task.
AB  - People's strategy selections appear to reflect attempts to maximize performance
      by selecting the most effective option for a particular task or format. Theories
      that account for such behaviour will be named rational models of strategy
      selection. However, it is possible to find instances where people are apparently
      biased towards using less effective strategies, and such behaviour appears to go
      against these models. Two experiments are reported in which participants were
      instructed to use first one, and then the other of two possible strategies for
      solving a compass point directions task (the instructed phase), and were
      subsequently permitted to use any strategy (the free-choice phase). A substantial
      minority of participants selected the less effective spatial strategy during the
      free-choice phase. Overall, it was found that people who rely on the spatial
      strategy when given a free-choice tend to be those who: (1) have not been given
      particular incentive to perform as well as possible; (2) have difficulty
      executing the better alternative, cancellation and (3) are particularly prone to
      making errors at the spatial strategy. Hence, although evidence was found in
      support of rational models of strategy selection, it is also suggested that these
      must additionally take account of the motivational and conceptual difficulties
      that people may have with a task.

PMID- 17535464
TI  - Divergent thinking: strategies and executive involvement in generating novel uses
      for familiar objects.
AB  - Although the Alternative Uses divergent thinking task has been widely used in
      psychometric and experimental studies of creativity, the cognitive processes
      underlying this task have not been examined in detail before the two studies are
      reported here. In Experiment 1, a verbal protocol analysis study of the
      Alternative Uses task was carried out with a Think aloud group (N=40) and a
      Silent control group (N=64). The groups did not differ in fluency or novelty of
      idea production indicating no verbal overshadowing. Analysis of protocols from
      the Think aloud group suggested that initial responses were based on a strategy
      of Retrieval from long-term memory of pre-known uses. Later responses tended to
      be based on a small number of other strategies: property-use generation, imagined
      Disassembly of the target object into components and scanning of Broad Use
      categories for possible uses of the target item. Novelty of uses was particularly
      associated with the Disassembly strategy. Experiment 2 (N=103) addressed the role
      of executive processes in generating new and previously known uses by examining
      individual differences in category fluency, letter fluency and divergent task
      performance. After completing the task, participants were asked to indicate which
      of their responses were new for them. It was predicted and found in regression
      analyses that letter fluency (an executively loading task) was related to
      production of 'new' uses and category fluency was related to production of 'old'
      uses but not vice versa.

PMID- 17535465
TI  - The role of semantic transparency in the processing of English compound words.
AB  - Experiment 1 examined whether the semantic transparency of an English unspaced
      compound word affected how long it took to process it in reading. Three types of
      opaque words were each compared with a matched set of transparent words (i.e.
      matched on the length and frequency of the constituents and the frequency of the
      word as a whole). Two sets of the opaque words were partially opaque: either the
      first constituent was not related to the meaning of the compound (opaque
      transparent) or the second constituent was not related to the meaning of the
      compound (transparent-opaque). In the third set (opaque-opaque), neither
      constituent was related to the meaning of the compound. For all three sets, there
      was no significant difference between the opaque and the transparent words on any
      eye-movement measure. This replicates an earlier finding with Finnish compound
      words (Pollatsek & Hyona, 2005) and indicates that, although there is now
      abundant evidence that the component constituents play a role in the encoding of
      compound words, the meaning of the compound word is not constructed from the
      parts, at least for compound words for which a lexical entry exists. Experiment 2
      used the same compounds but with a space between the constituents. This
      presentation resulted in a transparency effect, indicating that when an assembly
      route is 'forced', transparency does play a role.

PMID- 17535466
TI  - Cognitive and affective predictors of academic achievement in schoolchildren.
AB  - The ability of the theory of planned behaviour to predict objectively measured
      outcomes was tested in school-age children. Study 1 (N=71) showed that the theory
      of planned behaviour accounted for significant proportions of the variance in
      intention and that the intentions predicted scores in a science test; study 2
      (N=175) replicated these effects across a broader range of subjects. In addition,
      study 2 explored the mechanism by which intention was translated into action and
      demonstrated that intention stability moderated the intention-academic
      achievement relationship. Moreover, controlling for a range of cognitive and
      affective variables, intention and positive affect were independent predictors of
      intention stability. These findings suggest that although positive affect did not
      influence intention directly, it did influence intention stability, the mechanism
      by which intentions are translated into action. Future educational interventions
      should therefore influence both cognitive and affective factors to promote
      sustained motivation.

PMID- 17535467
TI  - Interrogative pressure in simulated forensic interviews: the effects of negative
      feedback.
AB  - Much experimental research on interrogative pressure has concentrated on the
      effects of leading questions, and the role of feedback in influencing responses
      in the absence of leading questions has been neglected by comparison. This study
      assessed the effect of negative feedback and the presence of a second interviewer
      on interviewee responding in simulated forensic interviews. Participants viewed a
      videotape of a crime, answered questions about the clip and were requestioned
      after receiving feedback. Compared with neutral feedback, negative feedback
      resulted in more response changes, higher reported state anxiety and higher
      ratings of interview difficulty. These results are consistent with Gudjonsson and
      Clark's (1986) model of interrogative suggestibility. The presence and
      involvement of a second interviewer did not significantly affect interviewee
      responding, although trait anxiety scores were elevated when a second interviewer
      was present. The theoretical and applied implications of these findings are
      considered.

PMID- 17535468
TI  - Personality and religious values among adolescents: a three-wave longitudinal
      analysis.
AB  - Using three waves of data, we assessed the relationships between endorsement of
      religious values, some of the major personality dimensions, and social and
      emotional well-being amongst teenagers. Participants were 784 high school
      students at Time 1 (382 males and 394 females; 8 did not indicate their gender)
      and 563 provided data at each of Time 1, Time 2 and Time 3. We examined the
      impact of changes in (Eysenckian) psychoticism and conscientiousness from Time 1
      to Time 2 on religious values assessed at Time 3. Both personality and
      personality change predicted religious values and the specific effects depended
      on gender. Participants higher in hope, joviality, psychological acceptance and
      mindfulness also tended to be higher in religious values. The implications of
      these results for adolescent well-being and resilience are discussed.

PMID- 17535469
TI  - Message framing with respect to decisions about vaccination: the roles of frame
      valence, frame method and perceived risk.
AB  - People respond differently when information is framed either positively or
      negatively (frame valence). Two prominent models propose that the effects of
      valence are moderated by (1) the method of framing (attributes vs. goals: Levin,
      Schneider, & Gaeth, 1998) and (2) perceived risk (Rothman & Salovey, 1997). This
      experiment (N=200) explores the joint influence of both of these moderators with
      respect to decisions about a flu vaccination. The study extends previous work by
      integrating these two models and exploring the moderating effects of two
      different aspects of perceived risk (personal outcome effectiveness and
      procedural risk). The results show that personal outcome effectiveness indirectly
      links frames to intentions. Procedural risk moderates the relationship between
      valence and method in a manner consistent with predictions from Levin et al..
      Partial support for the model proposed by Rothman and Salovey are observed for
      goal frames only.

PMID- 17535470
TI  - Digit ratio as an indicator of numeracy relative to literacy in 7-year-old
      British schoolchildren.
AB  - A great deal of recent research has focused upon the relationship between a
      hypothesized index of prenatal testosterone exposure, digit ratio and health,
      social and cognitive functioning. Many inconsistencies within the pattern of
      findings have been identified in the relationship between digit ratio and
      absolute levels of cognitive ability. Recent research has identified a
      relationship between digit ratio and basic numeric competency. This basic
      numerical competency has been argued to be influenced by biological factors. The
      present study extended this finding to academic assessment, namely the
      Standardized Assessment Tests undertaken in numeracy and literacy by children in
      the UK at the age of 7. The present study hypothesized that digit ratio would
      correlate with the relative difference between numeracy and literacy abilities.
      Digit ratios were calculated for 75 (mainly Caucasian) children aged between 6
      and 7 attending a state funded infant school. The digit ratios were then
      correlated with the results from their National Standard Assessment Tests (SATs).
      A significant correlation was found as hypothesized. Additionally, there was a
      negative correlation between digit ratio and numeracy for males (indicating
      higher prenatal testosterone exposure related to higher numeracy SAT scores) and
      a positive correlation between digit ratio and literacy for females (indicating
      lower prenatal testosterone exposure related to higher literacy SAT scores).
      These effects were small and the implications for using digit ratio to facilitate
      understanding of hormonal influences upon academic attainment are discussed.

PMID- 17535471
TI  - Contact, configural coding and the other-race effect in face recognition.
AB  - The other-race effect (ORE) in face recognition describes a well-established
      finding of better recognition for own-race than other-race faces. Although widely
      thought to reflect differences in contact between own- and other-race faces,
      little is known about how different contact levels relate to changes in
      processing of those faces. This study investigated how contact affects the size
      of the ORE and the use of expert configural face-coding mechanisms. Using
      inversion decrements as an index of configural coding, we predicted that
      increased self-reported contact would be associated with greater use of
      configural-coding mechanisms. Chinese and Caucasian participants varying in
      contact with other-race faces were recruited. The Chinese participants also
      varied in their length of residence in a Western country. Results showed that
      higher levels of contact were associated with a reduction in the ORE in both face
      recognition and configural coding. Importantly, smaller cross-race differences in
      configural coding were also associated with a smaller ORE in face recognition.

PMID- 17535472
TI  - Synaesthesia, creativity and art: what is the link?
AB  - It has been suggested that individuals with synaesthesia may show heightened
      creativity as a result of being able to form meaningful associations between
      disparate stimuli (e.g. colour, sound). In this study, a large sample (N=82) of
      people with various kinds of synaesthesia were given two psychometric tests of
      creativity (Remote Associates Test, Alternate Uses Test) and were also asked
      about the amount of time engaged in creative arts (visual art, music). There was
      a significant tendency for synaesthetes to spend more time engaged in creative
      arts and this was, at least in part, dependent upon the type of synaesthesia
      experienced. For example, synaesthetes experiencing vision from music were far
      more likely to play an instrument than their other synaesthetic counterparts.
      There was no relationship between this tendency and the psychometric measures of
      creativity, but synaesthetes did outperform controls on one of the two
      psychometric measures (Remote Associates). We conclude that the tendency for
      synaesthetes to be more engaged in art is likely to have a different mechanism to
      psychometric measures of creativity, and that there is no direct link between
      them. Although synaesthetes may well perform better on some measures of
      creativity, we suggest that synaesthetes have better bottom-up access to certain
      associations, but are not necessarily better able to use them flexibly (in
      divergent thinking).

PMID- 17535473
TI  - Subclinical delusional ideation and a self-reference bias in everyday reasoning.
AB  - Previous studies (e.g. Moller & Husby, 2000; Blackwood et al., 2004) have
      revealed that delusional thinking is accompanied by an exaggerated focus upon the
      self and upon stimuli that are perceived to be related to the self. The objective
      was to examine whether those high in subclinical delusional ideation exhibit a
      heightened tendency for self-reference. Using a mixed design, healthy
      individuals, classified into high- and low-scoring groups on the Peters et al.
      Delusions Inventory (Peters, Day, & Garety, 1996), were compared on everyday
      reasoning tasks across three experiments. High-PDI scorers, in contrast to the
      low-PDI group, rated self-referent objections to everyday arguments as stronger
      than other-referent objections and formulated more self-referent assertion-based
      objections to everyday arguments. The findings support the notion that
      subclinical delusional ideation is linked to a self-reference bias, which is
      evident in the sort of everyday thinking that people engage in when forming or
      evaluating their beliefs and which may contribute to delusion formation.

PMID- 17535474
TI  - Role of motion signals in recognizing subtle facial expressions of emotion.
AB  - Three studies investigated the importance of movement for the recognition of
      subtle and intense expressions of emotion. In the first experiment, 36 facial
      emotion displays were duplicated in three conditions either upright or inverted
      in orientation. A dynamic condition addressed the perception of motion by using
      four still frames run together to encapsulate a moving sequence to show the
      expression emerging from neutral to the subtle emotion. The multi-static
      condition contained the same four still presented in succession, but with a
      visual noise mask (200 ms) between each frame to disrupt the apparent motion,
      whilst in the single-static condition, only the last still image (subtle
      expression) was presented. Results showed a significant advantage for the dynamic
      condition, over the single- and multi-static conditions, suggesting that motion
      signals provide a more accurate and robust mental representation of the
      expression. A second experiment demonstrated that the advantage of movement was
      reduced with expressions of a higher intensity, and the results of the third
      experiment showed that the advantage for the dynamic condition for recognizing
      subtle emotions was due to the motion signal rather than additional static
      information contained in the sequence. It is concluded that motion signals
      associated with the emergence of facial expressions can be a useful cue in the
      recognition process, especially when the expressions are subtle.

PMID- 17535475
TI  - Adults' representations of the Earth: implications for children's acquisition of
      scientific concepts.
AB  - When children are asked to draw the Earth they often produce intriguing pictures
      in which, for example, people seem to be standing on a flat disc or inside a
      hollow sphere. These drawings, and children's answers to questions, have been
      interpreted as indicating that children construct naive, theory-like mental
      models of the Earth (e.g. Vosniadou & Brewer, 1992). However, recent studies
      using different methods have found little or no evidence of these mental models,
      and report that many young children have some scientific knowledge of the Earth.
      To examine the reasons for these contrasting findings, adults (N=350) were given
      the drawing task previously given to 5-year-old children. Fewer than half of the
      adults' pictures were scientific, and 15% were identical to children's 'naive'
      drawings. Up to half of the answers to questions (e.g. 'Where do people live?')
      were non-scientific. Open-ended questions and follow-up interviews revealed that
      non-scientific responses were given because adults found the apparently simple
      task confusing and challenging. Since children very probably find it even more
      difficult, these findings indicate that children's non-scientific responses, like
      adults', often result from methodological problems with the task. These results
      therefore explain the discrepant findings of previous research, and support the
      studies which indicate that children do not have naive mental models of the
      Earth.

PMID- 17535476
TI  - Comparing the squared multiple correlation coefficients of non-nested models: an
      examination of confidence intervals and hypothesis testing.
AB  - The performance of the asymptotic method for comparing the squared multiple
      correlations of non-nested models was investigated. Specifically, the increase in
      a given regression model's R2 when one predictor is added was compared to the
      increase in the same model's R2 when another predictor is added. This comparison
      can be used to determine predictor importance and is the basis for procedures
      such as Dominance Analysis. Results indicate that the asymptotic procedure
      provides the expected coverage rates for sample sizes of 200 or more, but in many
      cases much higher sample sizes are required to achieve adequate power. Guidelines
      and computations are provided for the determination of adequate sample sizes for
      hypothesis testing.

PMID- 17535477
TI  - A note on monotone likelihood ratio of the total score variable in unidimensional
      item response theory.
AB  - This note provides a direct, elementary proof of the fundamental result on
      monotone likelihood ratio of the total score variable in unidimensional item
      response theory (IRT). This result is very important for practical measurement in
      IRT, because it justifies the use of the total score variable to order
      participants on the latent trait. The proof relies on a basic inequality for
      elementary symmetric functions which is proved by means of few purely algebraic,
      straightforward transformations. In particular, flaws in a proof of this result
      by Huynh [(1994). A new proof for monotone likelihood ratio for the sum of
      independent Bernoulli random variables. Psychometrika, 59, 77-79] are pointed out
      and corrected, and a natural generalization of the fundamental result to non
      linear (quasi-ordered) latent trait spaces is presented. This may be useful for
      multidimensional IRT or knowledge space theory, in which the latent 'ability'
      spaces are partially ordered with respect to, for instance, coordinate-wise
      vector-ordering or set-inclusion, respectively.

PMID- 17535478
TI  - Wavelet modelling of collinearity judgment error.
AB  - Prior research has found that participants manifest complex profiles of error
      when they are asked to judge collinearity of stimulus elements. These studies
      used harmonic analysis to model the data, and found large departures from
      accurate collinear judgments, with the amplitude and specific angular position of
      departures from valid judgment varying from one participant to the next. The
      models appeared to be a composite of many large-, medium- and small-scale
      departures, but this could not be established with any certainty because of the
      global nature of harmonic model components. Wavelet modelling is better suited to
      answer the question of whether the error profile is produced by independent
      sources that vary in size and location. Here, we examined judgments of
      collinearity of dot pairs across 360 degrees of angular position. A priori and
      post hoc wavelet modelling strategies were used to identify independent sources
      of error that could not be attributed to chance, and some new statistical
      protocols were applied. We found evidence of error sources at several levels of
      scale, and these results were confirmed by the application of cross-validation
      methods that make no assumption about the nature of the error probability
      distribution.

PMID- 17535479
TI  - Stability analysis in K-means clustering.
AB  - This paper develops a new procedure, called stability analysis, for K-means
      clustering. Instead of ignoring local optima and only considering the best
      solution found, this procedure takes advantage of additional information from a K
      means cluster analysis. The information from the locally optimal solutions is
      collected in an object by object co-occurrence matrix. The co-occurrence matrix
      is clustered and subsequently reordered by a steepest ascent quadratic assignment
      procedure to aid visual interpretation of the multidimensional cluster structure.
      Subsequently, measures are developed to determine the overall structure of a data
      set, the number of clusters and the multidimensional relationships between the
      clusters.

PMID- 17535480
TI  - A dynamic extraversion model. The brain's response to a single dose of a
      stimulant drug.
AB  - The aim of this paper is to present a mathematical dynamic modelling of the
      effect a stimulant drug has on different people which, at the same time, can be a
      useful tool for future brain studies. To this end, a dynamic model of the
      evolution of extraversion (considering its tonic and phasic aspects) has been
      constructed taking into account the unique personality trait theory and the
      general modelling methodology. This model consists of a delayed differential
      equation which, on one hand, considers that the active stimulus, a consequence of
      a single intake, is not constant; on the other hand, it contemplates that the
      state variable representing the phasic extraversion also represents the brain
      activation. The derivative of this state variable is calculated as the sum of the
      homeostatic control flow, the excitatory effect flow and the inhibitor effect
      flow. The solutions of this equation relate the tonic activation of an individual
      (that characterizes his or her personality) with his or her phasic activation
      level, whose evolution over time describes the organism's response to a single
      drug intake. These solutions quantitatively reproduce the predictions of current
      personality theories and anticipate vulnerability to drug misuse and addiction
      development.

PMID- 17535481
TI  - A general diagnostic model applied to language testing data.
AB  - Probabilistic models with one or more latent variables are designed to report on
      a corresponding number of skills or cognitive attributes. Multidimensional skill
      profiles offer additional information beyond what a single test score can
      provide, if the reported skills can be identified and distinguished reliably.
      Many recent approaches to skill profile models are limited to dichotomous data
      and have made use of computationally intensive estimation methods such as Markov
      chain Monte Carlo, since standard maximum likelihood (ML) estimation techniques
      were deemed infeasible. This paper presents a general diagnostic model (GDM) that
      can be estimated with standard ML techniques and applies to polytomous response
      variables as well as to skills with two or more proficiency levels. The paper
      uses one member of a larger class of diagnostic models, a compensatory diagnostic
      model for dichotomous and partial credit data. Many well-known models, such as
      univariate and multivariate versions of the Rasch model and the two-parameter
      logistic item response theory model, the generalized partial credit model, as
      well as a variety of skill profile models, are special cases of this GDM. In
      addition to an introduction to this model, the paper presents a parameter
      recovery study using simulated data and an application to real data from the
      field test for TOEFL Internet-based testing.

PMID- 17535482
TI  - Alpha if item deleted: a note on loss of criterion validity in scale development
      if maximizing coefficient alpha.
AB  - This note is concerned with a validity-related limitation of the widely available
      and routinely used index 'alpha if item deleted' in the process of construction
      and development of multiple-component measuring instruments. Attention is drawn
      to the fact that this statistic can suggest dispensing with such scale
      components, whose removal leads to loss of criterion validity while maximizing
      the popular coefficient alpha. As an alternative, a latent variable modelling
      approach is discussed that can be used for point and interval estimation of
      composite criterion validity (as well as reliability) after deletion of single
      components. The method can also be utilized to test conventional or minimum level
      hypotheses about associated population change in measurement quality indices.

PMID- 17535483
TI  - Goodness-of-fit testing using components based on marginal frequencies of
      multinomial data.
AB  - The goodness-of-fit test based on Pearson's chi-squared statistic is sometimes
      considered to be an omnibus test that gives little guidance to the source of poor
      fit when the null hypothesis is rejected. It has also been recognized that the
      omnibus test can often be outperformed by focused or directional tests of lower
      order. In this paper, a test is considered for a model on a data table formed by
      the cross-classification of q dichotomous variables, and a score statistic on
      overlapping cells that correspond to the first- through qth-order marginal
      frequencies is presented. Then orthogonal components of the Pearson-Fisher
      statistic are defined on marginal frequencies. The orthogonal components may be
      used to form test statistics, and a log-linear version of an item response model
      is used to investigate the order and dilution of a test based on these
      components, as well as the projection of components onto the space of lower-order
      marginals. The advantage of the components in terms of power and detection of the
      source of poor fit is demonstrated. Overcoming the adverse effects of sparseness
      provides another motive for using components based on marginal frequencies
      because an asymptotic chi-squared distribution will be more reliable for a
      statistic formed on overlapping cells if expected frequencies in the joint
      distribution are small.

PMID- 17535484
TI  - Constructing second-order accurate confidence intervals for communalities in
      factor analysis.
AB  - In an effort to find accurate alternatives to the usual confidence intervals
      based on normal approximations, this paper compares four methods of generating
      second-order accurate confidence intervals for non-standardized and standardized
      communalities in exploratory factor analysis under the normality assumption. The
      methods to generate the intervals employ, respectively, the Cornish-Fisher
      expansion and the approximate bootstrap confidence (ABC), and the bootstrap-t and
      the bias-corrected and accelerated bootstrap (BC(a)). The former two are
      analytical and the latter two are numerical. Explicit expressions of the
      asymptotic bias and skewness of the communality estimators, used in the
      analytical methods, are derived. A Monte Carlo experiment reveals that the
      performance of central intervals based on normal approximations is a consequence
      of imbalance of miscoverage on the left- and right-hand sides. The second-order
      accurate intervals do not require symmetry around the point estimates of the
      usual intervals and achieve better balance, even when the sample size is not
      large. The behaviours of the second-order accurate intervals were similar to each
      other, particularly for large sample sizes, and no method performed consistently
      better than the others.

PMID- 17535485
TI  - On the linearity of predefined and self-anchoring Visual Analogue Scales.
AB  - Two functional measurement studies were conducted to test the effect of two types
      of end anchors on the linearity of Visual Analogue Scale (VAS) data. With the
      first type of end anchors, participants responded to the stimuli using a VAS with
      predefined end anchors. With the second type, respondents defined the end anchors
      in terms of their own assumptions, perceptions, goals and values. The results
      show that VASs can be considered as linear scales and that the type of end
      anchors used has no effect on the linearity of the VAS data.

PMID- 17535486
TI  - The true-change model with individual method effects: reliability issues.
AB  - The true intra-individual change model is generalized by defining individual
      method effects. This allows the analysis of non-congeneric test-retest variables
      assumed to measure a common, possibly (temporally) transient, attribute. Temporal
      change in the attribute between different times of measurement is modelled by the
      true-change variable. Individual causal method effects, due to heterogeneity of
      the measurement methods, account for the imperfect correlation of the true-score
      variables at each time of measurement. The reliability of the composite scores,
      at each time of measurement, and the reliability of the difference composite
      score may be estimated with appropriate coefficients derived from the model.
      Measurements of daily life tension in adult females serve to illustrate how the
      model can be used empirically.

PMID- 17535487
TI  - Generalized latent variable models with non-linear effects.
AB  - Until recently, item response models such as the factor analysis model for metric
      responses, the two-parameter logistic model for binary responses and the
      multinomial model for nominal responses considered only the main effects of
      latent variables without allowing for interaction or polynomial latent variable
      effects. However, non-linear relationships among the latent variables might be
      necessary in real applications. Methods for fitting models with non-linear latent
      terms have been developed mainly under the structural equation modelling
      approach. In this paper, we consider a latent variable model framework for mixed
      responses (metric and categorical) that allows inclusion of both non-linear
      latent and covariate effects. The model parameters are estimated using full
      maximum likelihood based on a hybrid integration-maximization algorithm. Finally,
      a method for obtaining factor scores based on multiple imputation is proposed
      here for the non-linear model.

PMID- 17535488
TI  - A longitudinal study of the relationship between psychological distress and
      recurrence of upper respiratory tract infections in chronic fatigue syndrome.
AB  - OBJECTIVES: Previous research has found that chronic fatigue syndrome (CFS)
      patients report increased susceptibility to upper respiratory tract illnesses
      (URTIs) when compared with healthy volunteers. This study aimed to replicate and
      extend this research by investigating the role of psychological distress (stress
      and negative mood) in the recurrence of URTIs in CFS patients as well as its role
      in the recurrence of CFS symptoms. DESIGN: A 15-week diary study. METHODS:
      Measures of psychological stress, negative mood, recurrence of URTIs and symptoms
      were recorded each week for a 15-week period. CFS patients (N=21), who had been
      assessed and diagnosed according to the Oxford criteria, were recruited from the
      Cardiff Chronic Fatigue Clinic and compared with a matched group of healthy
      controls (N=18). Frequency of occurrence of infectious illness and the
      relationship between psychological stress/negative mood and occurrence of illness
      were assessed. RESULTS: CFS patients reported more URTIs than the controls.
      Stress scores (and negative mood) were significantly higher in the week prior to
      the occurrence of URTIs than in weeks when no subsequent illness occurred. High
      levels of psychological stress also preceded the severity of reported symptoms of
      fatigue in the CFS group. CONCLUSIONS: CFS patients reported more frequent URTIs
      than healthy controls and these recurrences were preceded by high levels of
      psychological stress. High levels of stress were also associated with greater
      subsequent fatigue. Possible explanations of these results are discussed.

PMID- 17535489
TI  - Promoting children's fruit and vegetable consumption: interventions using the
      Theory of Planned Behaviour as a framework.
AB  - OBJECTIVE: This study compared a motivational intervention based on the Theory of
      Planned Behaviour (TPB) with a volitional intervention based on implementation
      intentions. DESIGN: The study employed a quantitative longitudinal questionnaire
      design involving two waves of data collection. METHOD: Participants (N=198) were
      randomly allocated to a control group or one of two intervention groups. TPB
      variables, and fruit and vegetable consumption were assessed at the beginning of
      the study (time 1) and 2 weeks later (time 2). Experimental group A formed an
      implementation intention, about how, when and where they could eat five portions
      a day, whilst experimental group B stated ways they could overcome motivational
      barriers to eating five portions a day. RESULTS: Both interventions were found to
      increase fruit and vegetable consumption significantly, although only the
      volitional intervention demonstrated a significant increase in fruit and
      vegetable consumption over the control intervention. CONCLUSIONS: The present
      study found support for two interventions in increasing fruit and vegetable
      consumption in children. These findings are encouraging regarding the use of
      these types of interventions within schools to improve children's eating
      behaviour.

PMID- 17535490
TI  - Can illness perceptions and coping predict psychological distress amongst allergy
      sufferers?
AB  - OBJECTIVE: The aim of the present study was to measure the extent to which
      illness perceptions and coping strategies are associated with the levels of
      psychological distress amongst allergy sufferers. DESIGN AND METHOD: One hundred
      and fifty-six allergy sufferers (all members of Allergy U.K.) completed a postal
      survey consisting of the Revised Illness Perception Questionnaire (IPQ-R) and the
      COPE. Psychological distress was measured using the General Health Questionnaire
      (GHQ-28) and the Perceived Stress Scale (PSS). RESULTS: Multiple regression
      analyses indicated that illness perceptions explained between 6 and 26% of
      variance on measures of psychological distress; coping strategies explained
      between 12 and 25%. A strong illness identity and emotional representations of
      the allergy were associated with higher levels of psychological distress; as were
      less adaptive coping strategies such as focusing on and venting of emotions.
      Strong personal control beliefs were associated with the lower levels of
      distress, as were adaptive coping strategies such as positive reinterpretation
      and growth. Coping partially mediated the link between the illness perceptions
      and the outcome; however, illness identity, emotional representations and
      personal control retained an independent significant association with
      psychological distress. CONCLUSION: The findings support a role for illness
      perceptions and coping in explaining levels of psychological distress amongst
      allergy sufferers. This has implications for targeted health interventions aimed
      at reducing the strength of illness identity and emotional representations and
      increasing a sense of control and the use of more adaptive coping strategies.

PMID- 17535491
TI  - How is persistent insomnia maintained? A prospective study on 50-60 years old
      adults in the general population.
AB  - OBJECTIVES: The purpose of this study was to examine whether arousal, distress
      and sleep-related beliefs are related to the maintenance of insomnia in old
      adults. DESIGN: From a randomly selected sample from the general population
      (N=3,600; 50-60 years old), 2,239 participants filled out a baseline and 1-year
      follow-up survey. METHODS: Logistic regressions were used to investigate whether
      psychological mechanisms were related to sleep status (insomnia: N=230; poor
      sleep: N=210; normal sleep: N=658; good sleep: N=253) over one year. Cluster
      analysis was employed to assess whether it was possible to classify the
      participants based on their profiles of psychological functioning. RESULTS: The
      results showed that arousal, sleep-related beliefs about future consequences and
      anxiety were significantly related to the maintenance of insomnia (14-66% of the
      variance). Out of the individuals with persistent insomnia, 67% belonged to a
      cluster characterized by high scores on arousal, sleep-related beliefs and
      anxiety, 24% to a cluster defined by medium scores on the three mechanisms and 9%
      to a cluster characterized by low scores on the three mechanisms. CONCLUSIONS:
      This investigation shows not only that arousal, sleep-related beliefs and anxiety
      are associated with the maintenance of persistent insomnia, but also that these
      mechanisms often co-occur in individuals with persistent insomnia.

PMID- 17535492
TI  - Trajectories and predictors of anxiety and depression in women during the 12
      months following an acute cardiac event.
AB  - OBJECTIVES: Many previous investigations of the recovery of emotional well-being,
      particularly the resolution of depression, following an acute cardiac event
      assume that all patients follow a similar, linear trajectory. However, it is
      possible that there are different groups of patients who follow different
      trajectories. This study tested for multiple trajectories of anxiety and
      depression and identified the characteristics of patients most at risk for
      persistent or worsening anxiety and depression in the 12 months following their
      cardiac event. METHOD: A consecutive sample of 226 women was interviewed
      following either acute myocardial infarction (AMI) or coronary artery bypass
      graft surgery (CABGS). The Hospital Anxiety and Depression Scale were
      administered on four occasions over 12 months. Growth curve and growth mixture
      modelling were used to identify trajectories of change and univariate tests were
      employed to establish predictors of each trajectory. RESULTS: Most women began
      with relatively low levels of anxiety and/or depression that improved over the 12
      month period (84% women showed this trajectory for anxiety, 89% for depression).
      A smaller group began with relatively high levels of anxiety and/or depression
      that worsened over time (16% for anxiety, 11% for depression). Patients in the
      latter group were more likely to report high levels of loneliness, have a first
      language other than English, perceive their cardiac disease as more severe
      (anxiety group only) and have diabetes (depression group only). Trajectories were
      non-linear, with most change occurring in the initial 2-month period. CONCLUSION:
      Growth modelling techniques highlight that change in anxiety and depression
      following an acute event follows neither a single nor linear trajectory. Most
      women showed early resolution of anxiety and depression following their event,
      indicative of a normal bereavement or adjustment response. A minority of women
      reported worsening anxiety and/or depression in the year following their cardiac
      event, particularly those who lacked social support or were from non-English
      speaking backgrounds. Intervention studies to explore support options for these
      women are warranted, both prior to and following their event.

PMID- 17535493
TI  - Effects of abstinence from habitual involvement in regular exercise on feeling
      states: an ecological momentary assessment study.
AB  - Regular exercise was experimentally reduced to determine its effects on positive
      feeling states. Using ecological momentary assessments, 40 participants
      maintained their regular exercise routine on 3 days and were deprived of their
      scheduled exercise on 3 other days. They recorded their feeling states, using the
      Exercise-Induced Feeling Inventory, four times daily as well as prior to and
      following exercise. Multi-level modelling analyses controlling for diurnal
      variations in feeling states revealed that positive feeling states were elevated
      on days when exercise deprivation occurred compared with non-exercise days and
      when no deprivation manipulation occurred. People with lower exercise dependence
      symptoms felt better on days when they were deprived from exercise compared with
      non-exercise days, whereas people with higher exercise dependence symptoms felt
      about the same when they were deprived from exercise compared with non-exercise
      days. These findings demonstrate that positive feeling states occur following an
      acute bout of exercise and that exercise deprivation had a positive impact on
      feeling states, with the level of exercise dependence symptoms moderating this
      effect.

PMID- 17535494
TI  - Exposure to and fear of terror as predictors of self-rated health among
      apparently healthy employees.
AB  - The effects of exposure to terror on physical health were investigated by
      relating objective exposure to terror and fear of terror to self-rated health
      (SRH), a proxy measure of health status. Our respondents were apparently healthy
      (N=4,877, 38% women) adults who completed self-report questionnaires. Objective
      exposure was assessed by the number of terrorist attacks and their casualties in
      a respondent's urban area prior to her/his completion of the questionnaire. Using
      several alternative assessments, objective exposure to terror did not predict SRH
      for both the genders. As hypothesized, fear of terror negatively predicted SRH
      for both females and males (beta=-0.04, -0.05, respectively). The effects of
      subjective and objective exposure were not found to be more pronounced among
      women relative to men, thus disconfirming our hypotheses in this regard. Our
      findings suggest that living under continuous fear of terror may adversely
      influence physical health irrespective of objective exposure.

PMID- 17535495
TI  - Comparing neuropsychological function before and during haemodialysis: a
      habituating selective deficit for prose recall.
AB  - This study was based on the clinical observation that patients receiving
      haemodialysis(HD) showed poor retention for complex verbal information. To
      investigate this hypothesis, 45 patients with endstage renal disease were
      administered a neuropsychological (NP) test battery, including a test of prose
      recall on two occasions, 7 days apart (pre-dialysis and whilst dialysing). A
      range of demographic, biochemical and mood variables were also assessed. Results
      revealed a selective deficit for prose recall whilst dialysing compared to pre
      dialysis performance, which habituated in the long-term. Possible physiological
      and psychological bases of these effects in HD patients are discussed.

PMID- 17535496
TI  - It has certainly been good just to talk: an interpretative phenomenological
      analysis of coping with myocardial infarction.
AB  - OBJECTIVES: The experience of a myocardial infarction (MI), its potential meaning
      and consequences arouse a high level of emotional responsiveness in the
      individual. Researchers to date have argued that implementing adaptive coping
      strategies is necessary for emotional adjustment. This study aimed to advance
      coping research by providing more detailed insight into middle-aged men's
      personal experiences of coping with MI and the meaning they ascribe to these
      experiences. DESIGN: Interpretative Phenomenological Analysis (IPA) was used to
      conduct an in-depth study of a small sample of patients who had suffered their
      first MI. METHOD: Semi-structured interviews were conducted with six men within 6
      months of their first MI. Verbatim transcripts of these interviews were analysed
      using IPA. RESULTS: Three superordinate themes emerged, which are described under
      the headings of 'Difficulty in Reflecting', 'Needing to Talk' and 'Back to
      Normal'. CONCLUSIONS: Participants seemed to share difficulties in reflecting on
      their coping strategies and the concept of coping generally, but were keen to
      talk about specific events in relation to the MI. The findings suggest that
      cardiac rehabilitation needs to focus on individual priorities for recovery.
      Providing opportunities for patients to talk through their experiences
      individually may be an important aspect of such care. Further research is needed
      to investigate the challenges that patients confront and the support they require
      post-MI.

PMID- 17535497
TI  - The role of resilience on psychological adjustment and physical health in
      patients with diabetes.
AB  - OBJECTIVE: This study used a longitudinal design to investigate the buffering
      role of resilience on worsening HbA(1c) and self-care behaviours in the face of
      rising diabetes-related distress. METHOD: A total of 111 patients with diabetes
      completed surveys and had their glycosylated haemoglobin (HbA(1c)) assessed at
      baseline and at 1-year follow-up. Resilience was defined by a factor score of
      self-esteem, self-efficacy, self-mastery and optimism. Diabetes-related distress
      and self-care behaviours were also assessed. RESULTS: Baseline resilience,
      diabetes-related distress and their interaction predicted physical health
      (HbA(1c)) at 1 year. Patients with low, moderate and high resilience were
      identified. Those with low or moderate resilience levels showed a strong
      association between rising distress and worsening HbA(1c) across time (r=.57,
      .56, respectively). However, those with high resilience scores did not show the
      same associations (r=.08). Low resilience was also associated with fewer self
      care behaviours when faced with increasing distress (r=-.55). These correlation
      coefficients remained significant after controlling for starting-points.
      CONCLUSION: In patients with diabetes, resilience resources predicted future
      HbA(1c) and buffered worsening HbA(1c) and self-care behaviours in the face of
      rising distress levels.

PMID- 17535498
TI  - Predicting the intention to quit smoking and quitting behaviour: extending the
      theory of planned behaviour.
AB  - OBJECTIVES: The present study examined the ability of the TPB to predict the
      intention to quit smoking and quitting behaviour. In addition, the predictive
      power of future orientation, number of cigarettes smoked, planning, past
      behaviour and the interactions between intention and other predictors was
      examined. MATERIAL AND METHODS: The data were derived from a longitudinal survey
      among 103 daily smoking students at the University of Oslo (mean age 24.6 years,
      mean number of years of smoking = 8 years). These data were collected by means of
      self-administered questionnaires at T1 (October 2003) and at T2 (February 2004)
      in terms of recording actual quitting. RESULTS: The TPB components accounted for
      30% of the variance in quitting intentions, and affective attitude and
      descriptive norm emerged as the strongest predictors of quitting intention.
      Ordinal regression analysis showed that intention was a borderline significant
      predictor of subsequent quitting behaviour, while the impact of PBC was non
      significant (model 1). The inclusion of the additional variables improved the fit
      of the model, with number of cigarettes and planning appearing as significant
      predictors of behaviour (model 2). As predicted, there was a significant
      interaction between perceived control and intentions on quitting (model 3).
      Nagelkerke R(2) increased from .07 in model 1 to .54 in model 2, and finally to
      .58 in model 3. CONCLUSIONS: The results indicate that affective attitude and
      descriptive norm play a more crucial role than the other TPB predictors in
      motivating smokers to quit. The results also indicate that self-regulatory
      strategies are important in relation to addictive behaviours.

PMID- 17535499
TI  - It's just the worry about not being able to control it! A qualitative study of
      living with overactive bladder.
AB  - OBJECTIVES: This study reports the perceptions of patients with a diagnosis of
      OAB and people with undiagnosed OAB symptoms about their health-related quality
      of life (HRQL) and psychological consequences. DESIGN: A qualitative study which
      employed a series of in-depth, semi-structured individual and group interviews
      using thematic and interpretive techniques of data analysis. METHODS: A mixture
      of previously diagnosed patients and people bothered by OAB symptoms were
      recruited from three British cities. The interviews explored issues around HRQL.
      Data were transcribed verbatim and analysed thematically to draw out the context
      in which people experience OAB. The study design was reviewed by a Multi-Centre
      Research Ethics Committee and subjected to local research governance. RESULTS:
      OAB has devastating consequences for sufferers of both sexes which impact upon
      their HRQL, self-esteem and relationships. OAB without incontinence causes
      anxiety, fear of incontinence, a sense of depression and hopelessness all of
      which are worse for those with incontinence. Many sufferers feel too embarrassed
      to seek medical care. CONCLUSIONS: The psychological and HRQL consequences for
      OAB sufferers overlap with trajectories associated with chronic illness. However,
      because many sufferers avoid admitting to the condition and/or seeking treatment
      the psychological costs to them are even greater than with a diagnosed illness
      because the disruption remains unacknowledged and therefore unresolved.

PMID- 17535500
TI  - Post-disaster physical symptoms of firefighters and police officers: role of
      types of exposure and post-traumatic stress symptoms.
AB  - OBJECTIVES: To examine the relationships between exposure to the air disaster in
      Amsterdam and multiple physical symptoms among firefighters and police officers,
      and to explore the role of post-traumatic stress symptoms (PTSS) herein. DESIGN:
      Historic cohort study. METHODS: On average 8.5 years post-disaster, exposed
      professional firefighters (N=334) and police officers (N=834) and their
      nonexposed colleagues (N=194 and N=634, respectively) completed questionnaires on
      disaster exposure and current symptoms. Logistic regression with adjustment for
      background characteristics was used to compare exposed and nonexposed workers.
      PTSS were added to these models, as was the interaction between exposure and
      PTSS, to explore potential mediating and modifying effects, respectively.
      RESULTS: Exposed workers reported multiple physical symptoms significantly more
      often. Multiple physical symptoms seemed to have particularly affected the
      exposed firefighters who rescued people, and the exposed police officers who
      supported injured victims and workers, who were involved in the identification of
      or search for victims and human remains, who witnessed the immediate disaster
      scene or had a close one affected by the disaster. These exposure effects were
      essentially independent of PTSS, and no significant interactions between exposure
      and PTSS were found. CONCLUSIONS: In conclusion, the excess in post-disaster
      multiple physical symptoms in exposed workers could not be attributed to PTSS.

PMID- 17535501
TI  - Modelling change in adolescent smoking behaviour: stability of predictors across
      analytic models.
AB  - OBJECTIVES: The current paper examined the variability of predictors of changes
      in adolescent smoking across linear and nonlinear analytic models. DESIGN: Three
      analytic models typically used to model adolescent smoking behaviour were tested:
      one linear model of change (standard linear), one static linear model (pre-post
      linear) and one nonlinear model of change (cusp catastrophe). Variability in
      model composition was assessed by examining the pattern of variables achieving
      statistical significance and proportion of variance explained. METHODS: Model
      testing was conducted on data from Australian adolescents successfully tracked
      through a 12-month longitudinal study of smoking (N = 779). The survey measured
      demographics, self-reported smoking, smoking among friends and family, self
      esteem, neuroticism, coping, stress and risk taking. RESULTS: The results
      indicated that while predictors of change were invariant across analytic models
      explanatory power varied markedly. Models of change in smoking that included
      simple, interacted or polynomial forms of initial conditions (past behaviour)
      explained more than four times the variance of models without. CONCLUSIONS: These
      results justified confidence in the predictors of change in adolescent smoking
      across analytic models. A secondary implication was that more research into past
      behaviour's role in the context of dynamical models of adolescent smoking and
      other health behaviour is needed.

PMID- 17535502
TI  - Using the demand-control model of job strain to predict caregiver burden and
      caregiver satisfaction in the informal caregivers of heart failure patients.
AB  - OBJECTIVES: The demand-control (D-C) model of job strain has generated a
      considerable body of empirical support in predicting psychological health
      outcomes in the context of work. This study aimed to extend previous work using
      the D-C model of job strain to predict caregiver burden and satisfaction in the
      informal caregivers of patients with heart failure. DESIGN AND METHOD: Data were
      gathered from 60 caregiver/patient dyads in a cross-sectional design. Patients
      with chronic stable heart failure were recruited from out-patient clinics. The
      dependent variables were caregiver burden and satisfaction. Demand and control
      were measured using both patient- and caregiver-derived measures. RESULTS: The D
      C model accounted for 15 and 19% of the variance in caregiver burden, after
      controlling for age, gender and relationship to the patient. Lower control was
      associated with higher burden. The D-C model did not predict caregiver
      satisfaction. CONCLUSION: The D-C model was associated with caregiver burden, but
      not satisfaction in caregivers, with control being the dominant predictor.
      Research linking the theory and findings from job strain and informal caregiving
      studies may elucidate both fields of research. Using the demand-control model of
      job strain to predict caregiver burden and caregiver satisfaction in the informal
      caregivers of heart failure patients.

PMID- 17535503
TI  - Improving outcomes for COPD patients with mild-to-moderate anxiety and
      depression: a systematic review of cognitive behavioural therapy.
AB  - PURPOSE: Anxiety and depression are highly prevalent in patients with chronic
      obstructive pulmonary disease (COPD) and are associated with lower levels of self
      efficacy, impaired health status, poorer treatment outcomes and reduced survival
      following emergency admission. Cognitive behavioural therapy (CBT) may be
      effective for treating anxiety and depression in COPD patients but evidence for
      this is uncertain. METHODS: A systematic review of controlled trials that
      evaluated the effectiveness of CBT for treating mild-to-moderate anxiety or
      depression in adults with clinically stable COPD. Ovid electronic bibliographic
      databases were searched from inception to May 2006; all content held by the
      Cochrane Library Issue 3, 2006 was also searched. RESULTS: One small randomized
      controlled trial (RCT) of moderate quality showed that CBT, when given with
      exercise training and education, was associated with large and significant
      treatment effects for both anxiety (-1.39 (95% CIs -2.19, -0.59)) and depression
      (-0.86 (95% CIs -1.61, -0.11)). Additionally, a larger RCT of higher quality
      demonstrated that CBT, when given with exercise and education, was associated
      with large and significant treatment effects for depression (-0.76 (95% CIs 
      1.34, -0.17)), but not for anxiety. No other included study reported significant
      reductions in either anxiety or depression in COPD patients given CBT.
      CONCLUSION: There is only limited evidence that CBT, when used with exercise and
      education, can contribute to significant reductions in anxiety and depression in
      COPD patients. There is scope for a well-powered RCT to evaluate the
      effectiveness and acceptability of CBT among this patient population.

PMID- 17535504
TI  - Pre-bereavement meaning and post-bereavement distress in mothers of children who
      underwent haematopoietic stem cell transplantation.
AB  - OBJECTIVES: The purpose of this study was to explore the association of meaning
      making with psychological adjustment to bereavement among mothers of children who
      had undergone haematopoietic stem cell transplantation (HSCT). DESIGN: A
      prospective research design was used. Regression analyses were conducted to
      determine the relations between pre-bereavement variables (distress, searching
      for meaning, and finding meaning) and distress post-bereavement. METHODS: Thirty
      five mothers of children who had undergone HSCT were interviewed at the time of
      their child's HSCT and 3 months post-bereavement. RESULTS: Mothers who reported
      searching for meaning at HSCT reported greater post-bereavement distress, and
      mothers who reported finding meaning at HSCT reported less post-bereavement
      distress. Distress at HSCT and the number of days between the time of death and
      the post-bereavement time point were also found to be significant predictors of
      post-bereavement distress. CONCLUSIONS: This study provides partial support for
      the role of meaning in adjustment to loss.

PMID- 17535505
TI  - Cognitive appraisals, distress and disability among persons in low vision
      rehabilitation.
AB  - OBJECTIVE: Examined cognitive appraisals of interference and tolerance in the
      prediction of distress and self-reported disability among persons presenting for
      low vision rehabilitation. DESIGN: Cross-sectional; correlational and path
      analyses. METHODS: One-hundred and thirteen patients (mean age, 71 years; 52 men
      and 61 women) presenting for low vision rehabilitation at a university-based
      centre for low vision rehabilitation participated in an initial clinical vision
      examination and completed several questionnaires to evaluate cognitive
      appraisals, emotional distress and self-reported disability. RESULTS: Path
      analyses indicated that greater tolerance was associated with less interference
      imposed by vision loss. Greater tolerance was also associated with less emotional
      distress and symptom severity (visual acuity) was associated with self-reported
      disability. Cognitive appraisals (tolerance and interference) indirectly
      influenced self-reported disability through emotional distress. CONCLUSIONS: The
      data indicate that appraisals of personal ability to tolerate vision loss and the
      perceived interference of vision loss on goal-directed behaviour and expected
      activities have greater influence on distress and are subsequently predictive of
      disability in comparison with objective symptoms (visual acuity). Implications
      for clinical interventions and further research are discussed.

PMID- 17535506
TI  - Testing an extended theory of planned behaviour to predict young people's sun
      safety in a high risk area.
AB  - OBJECTIVES: The present research examined the sun protection intentions and
      behaviours of young people in a high risk skin cancer area using an extended
      theory of planned behaviour (TPB) incorporating additional social influences of
      group and image norms. DESIGN: The study employed a prospective design to examine
      young people's sun protection intentions and behaviour. METHOD: Participants
      (N=1,134), aged 12-20 years, were students (school, university, TAFE) and young
      employees living in Queensland, Australia. Participants completed a questionnaire
      assessing the TPB predictors (attitude, subjective norm, perceived behavioural
      control) and additional social influences (group norm, image norm) of sun
      protection intentions. Two weeks later, participants (N=734) reported their sun
      protection behaviour for the previous fortnight. RESULTS: Results revealed that
      the TPB variables of attitude, subjective norm and perceived behavioural control
      and the additional social influence variable of group norms, but not image norms,
      emerged as significant predictors of intentions to engage in sun protection. The
      extended TPB variables accounted for 36% of the variance in intentions. For
      behaviour, the extended TPB variables accounted for 27% of the variance with both
      intention and, unexpectedly, group norm as the significant direct predictors of
      sun protective behaviours. CONCLUSIONS: Results of this study provide support for
      the application of the TPB in the sun safety context and highlight the importance
      of considering the influence of group norms in the development of future
      interventions to increase young people's sun protection intentions and behaviour.

PMID- 17535507
TI  - Cooperative learning in third graders' jigsaw groups for mathematics and science
      with and without questioning training.
AB  - BACKGROUND: There is much support for using cooperative methods, since important
      instructional aspects, such as elaboration of new information, can easily be
      realized by methods like 'jigsaw'. However, the impact of providing students with
      additional help like a questioning training and potential limitations of the
      method concerning the (minimum) age of the students have rarely been
      investigated. AIMS: The study investigated the effects of cooperative methods at
      elementary school level. Three conditions of instruction were compared: jigsaw,
      jigsaw with a supplementary questioning training and teacher-guided instruction.
      SAMPLE: Nine third grade classes from three schools with 208 students
      participated in the study. In each school, all the three instructional conditions
      were realized in three different classes. METHODS: All classes studied three
      units on geometry and one unit on astronomy using the assigned instructional
      method. Each learning unit comprised six lessons. For each unit, an achievement
      test was administered as pre-test, post-test and delayed test. RESULTS: In the
      math units, no differences between the three conditions could be detected. In the
      astronomy unit, students benefited more from teacher-guided instruction.
      Differential analyses revealed that 'experts' learned more than students in
      teacher-guided instruction, whereas 'novices' were outperformed by the students
      in the control classes. CONCLUSIONS: Even third graders used the jigsaw method
      with satisfactory learning results. The modest impact of the questioning training
      and the low learning gains of the cooperative classes in the astronomy unit as
      well as high discrepancies between learning outcomes of experts and novices show
      that explicit instruction of explaining skills in combination with well
      structured material are key issues in using the jigsaw method with younger
      students.

PMID- 17535508
TI  - Effects of competition on students' self-efficacy in vicarious learning.
AB  - BACKGROUND: Vicarious learning is one of the fundamental sources of self-efficacy
      that is frequently employed in educational settings. However, little research has
      investigated the effects of competition on students' writing self-efficacy when
      they engage in vicarious learning. AIM: This study compared the effects of
      competitive and non-competitive classrooms on students' writing self-efficacy
      when they engaged in vicarious learning. SAMPLE: The participants were 71 grade 7
      students in Hong Kong. METHOD: Using prior writing performance for stratified
      random sampling, students were assigned either to a competitive or a non
      competitive classroom. Students learned how to compose similes and metaphors in
      Chinese. RESULTS: In the competitive classroom, students' self-efficacy decreased
      when they engaged in vicarious learning. In the non-competitive classroom,
      students' self-efficacy did not show a significant change when they engaged in
      vicarious learning. CONCLUSION: The findings suggested that when students engaged
      in vicarious learning in a competitive classroom, their self-efficacy might be
      threatened. Implications for efforts to design constructive context for vicarious
      learning are discussed.

PMID- 17535509
TI  - University students' academic performance: an integrative conceptual framework
      and empirical analysis.
AB  - BACKGROUND: The prediction and explanation of academic performance and the
      investigation of the factors relating to the academic success and persistence of
      students are topics of utmost importance in higher education. AIMS: The main aim
      of the present study is to develop and test a conceptual framework in a
      university context, where the effects of achievement goals, self-efficacy and
      class size on academic performance are hypothesized to be direct and indirect
      through study strategies. SAMPLE: Participants were 553 students of different
      faculties from a university in Spain. METHOD: Pre-existing scales were used to
      develop the questionnaire. Questionnaires were group-administered in 21 classes
      during the first 2 weeks of May (i.e. about 1 month before the final
      examination). At the end of the academic year, students' grades were obtained
      from professors of each course. RESULTS: Data were analysed through structural
      equation modelling. The results of the structural model provided support for most
      of the hypothesized relationships. Achievement goals and self-efficacy had no
      direct effects on performance, but results from the model comparison suggested
      that a mediational model provided a better fit to the data. CONCLUSIONS: Our
      study provides support for the key mediational role of study strategies in the
      effect of achievement goals and self-efficacy on academic performance. Self
      efficacy seems to have the strongest indirect effect on performance. Mastery
      goals play a key role increasing deep processing and effort, and in turn
      affecting performance. Academic performance tends to diminish with increasing
      class size.

PMID- 17535510
TI  - Collaborative philosophical inquiry for schoolchildren: cognitive gains at 2-year
      follow-up.
AB  - BACKGROUND: Evidence of maintained gains from thinking skills interventions are
      rare in the literature even within sectors of education, let alone across
      sectors. AIMS: This study investigated the cognitive effects of collaborative
      philosophical inquiry at long-term 2-year follow-up, after the participants had
      transferred to secondary (high) school without experiencing further philosophical
      inquiry in the interim. SAMPLE: Sample attrition was greater in the control than
      in the experimental group, but 96 experimental and 52 control subjects were
      available. METHOD: Intervened children who engaged in collaborative inquiry for 1
      hour per week over 16 months and whose pre-post cognitive gains were reported in
      Topping and Trickey (2007) were followed up 2 years later, some time after they
      had transferred from primary to secondary school, again using the Cognitive
      Abilities Test. RESULTS: The significant pre-post cognitive ability gains in the
      experimental group in primary school were maintained towards the end of their
      second year of secondary school. Higher achieving pupils were somewhat advantaged
      in sustaining these gains. The control group showed an insignificant but
      persistent deterioration in scores from pre- to post-test to follow-up.
      CONCLUSIONS: Given the pattern of sample attrition, the group difference seems
      likely to be underestimated. The study provides evidence of maintained cognitive
      gains from collaborative philosophical inquiry, transferred across contexts.
      Implications for future research, policy and practice are discussed.

PMID- 17535511
TI  - Dispositional and situational learning goals and children's self-regulation.
AB  - BACKGROUND: Little research has examined interactions between self-reported
      dispositional and experimentally manipulated situational group orientations in
      their effect on self-regulation. AIMS: The aim of the study was to investigate
      the effect of dispositional and situational learning goal orientation on
      children's self-efficacy and engagement and persistence at a puzzle task. SAMPLE:
      A self-report learning goal orientation scale was completed by 110 children, aged
      9-11 years. Fifty-three children (24 girls) selected to be high and low on the
      scale participated in the experiment. METHODS: Half of the children were given
      instructions designed to evoke learning goals, while the remainder received
      performance goal instructions. Children attempted a difficult puzzle task on two
      occasions, when measures were made of self-regulatory behaviours. RESULTS AND
      CONCLUSIONS: Children assigned to the learning goal instruction were more likely
      to persist at the task until the end of the allotted time, displayed more on-task
      behaviour and engaged in more autonomous help-seeking. These effects were more
      pronounced following the first task, which all children had been unable to
      complete. Dispositional task orientation did not predict individual differences
      on these measures. The findings are interpreted in terms of learned helplessness
      and self-worth theory.

PMID- 17535512
TI  - Changes in high-school students' competence beliefs, utility value and
      achievement goals in mathematics.
AB  - BACKGROUND: Many studies have revealed that there is a significant decrease over
      time in high-school students' attitudes towards mathematics learning. Some
      authors conclude that motivation in mathematics stabilizes or improves around
      grade 9; others propose that the decline is continuous. It is unclear if girls or
      boys are more affected by this phenomenon. AIMS: The present study aims to
      further examine changes in competence beliefs, utility value and achievement
      goals in mathematics during high school, taking gender and period of the academic
      year into account. SAMPLE: 1,130 participants from 18 secondary schools,
      distributed in two cohorts (grades 7 and 9). METHOD: Attitudinal scales designed
      to measure competence beliefs, utility value and achievement goals in mathematics
      were administered at the beginning and end of three academic years in a
      longitudinal cohort-sequential research design using two sequential cohorts.
      Hierarchical linear modelling was used to analyse the data. RESULTS: Results
      showed an ongoing reduction of most of the variables measured. This was the case
      for both cohorts and genders. However, boys were more affected than girls.
      Furthermore, for all variables, motivation tended to be lower at the end of the
      academic year than at the beginning. CONCLUSIONS: Our results support the
      hypothesis of a regular decline of motivation in mathematics during high school,
      accentuated between grades 9 and 11. Moreover, our results illustrate gender
      convergence in mathematics rather than gender differentiation. Finally, the
      gradual drop in motivation in mathematics appears to be a two-step phenomenon: a
      decrease between and within grade levels.

PMID- 17535513
TI  - Influence of situational and conceptual rewording on word problem solving.
AB  - BACKGROUND: Studies on rewording word problems can be grouped into two main
      groups: situational rewording, in which the situation denoted by the text is
      described more richly, and conceptual rewording, in which the underlying semantic
      relations are highlighted. AIMS: Our aims are to define and distinguish these two
      kinds of rewording and to test empirically their relative effectiveness in two
      different studies. SAMPLE: In the first study, 79 third graders, 64 fourth
      graders and 65 fifth graders took part; the sample for Study 2 was similar.
      METHOD: In Study 1, children were asked to solve both easy and difficult two-step
      change problems in three different versions: standard, situational and conceptual
      rewording. In Study 2, three different versions of the situational version were
      compared: one with only temporal elaborations, one with only causal elaborations
      and a 'complete' version combining both elaborations. RESULTS: In Study 1,
      conceptually reworded problems elicited the best results, especially among
      younger children and for difficult two-step problems. Neither in Study 1 nor in
      Study 2 did the situationally reworded problems yield better performance than
      standard items. CONCLUSION: Only conceptual rewording has proved to be useful for
      improving children's performance, especially among younger children and for
      difficult problems. The lack of impact of situational rewording cannot be
      explained in terms of the length of the resulting text.

PMID- 17535514
TI  - University students' emotions, interest and activities in a web-based learning
      environment.
AB  - BACKGROUND: Within academic settings, students experience varied emotions and
      interest towards learning. Although both emotions and interest can increase
      students' likelihood to engage in traditional learning, little is known about the
      influence of emotions and interest in learning activities in a web-based learning
      environment (WBLE). AIMS: This study examined how emotions experienced while
      using a WBLE, students' interest towards the course topic and interest towards
      web-based learning are associated with collaborative visible and non
      collaborative invisible activities and 'lurking' in the WBLE. SAMPLE:
      Participants were 99 Finnish university students from five web-based courses.
      METHODS: All the students enrolled in the courses filled out pre- and post-test
      questionnaires of interest, and repeatedly completed an on-line questionnaire on
      emotions experienced while using the WBLE during the courses. RESULTS: The
      fluctuation of emotional reactions was positively associated with both visible
      collaborative and invisible non-collaborative activities in the WBLE. Further,
      interest towards the web-based learning was positively associated with invisible
      activity. The results also demonstrated that students not actively participating
      in the collaborative activities (i.e. lurkers) had more negative emotional
      experiences during the courses than other students. CONCLUSION: The results
      highlight the distinct impacts that emotions and interest have on different web
      based learning activities and that they should be considered when designing web
      based courses.

PMID- 17535515
TI  - Predicting change in epistemological beliefs, reflective thinking and learning
      styles: a longitudinal study.
AB  - BACKGROUND: Although extensive research has examined epistemological beliefs,
      reflective thinking and learning approaches, very few studies have looked at
      these three theoretical frameworks in their totality. AIMS: This research tested
      two separate structural models of epistemological beliefs, learning approaches,
      reflective thinking and academic performance among tertiary students over a
      period of 12 months. SAMPLE: Participants were first-year Arts (N=616; 271
      females, 345 males) and second-year Mathematics (N=581; 241 females, 341 males)
      university students. METHOD: Students' epistemological beliefs were measured with
      the Schommer epistemological questionnaire (EQ, Schommer, 1990). Reflective
      thinking was measured with the reflective thinking questionnaire (RTQ, Kember et
      al., 2000). Student learning approaches were measured with the revised study
      process questionnaire (R-SPQ-2F, Biggs, Kember, & Leung, 2001). LISREL 8 was used
      to test two structural equation models - the cross-lag model and the causal
      mediating model. RESULTS: In the cross-lag model involving Arts students,
      structural equation modelling showed that epistemological beliefs influenced
      student learning approaches rather than the contrary. In the causal-mediating
      model involving Mathematics students, the results indicate that both
      epistemological beliefs and learning approaches predicted reflective thinking and
      academic performance. Furthermore, learning approaches mediated the effect of
      epistemological beliefs on reflective thinking and academic performance. Results
      of this study are significant as they integrated the three theoretical frameworks
      within the one study.

PMID- 17535516
TI  - Bullying and victimization at school: the role of mothers.
AB  - BACKGROUND: Social learning literature is used in order to describe the
      contextual parameters of peer aggression, and specifically bullying and
      victimization. AIM: The aim of the present study was to examine the influence of
      maternal characteristics on their child's victimization or bullying experience at
      school. SAMPLE: The participants were 252 elementary school students (mean age
      11.5 years) and their mothers. METHOD: A theoretically driven model was developed
      and its ability to fit the data was tested. The main factors included in the
      model were the following: parental style as perceived by the child, self-reported
      parental involvement, the mother's emotional state and the degree of
      victimization experienced by the child at school. RESULTS: Through confirmatory
      factor analysis, it was shown that maternal responsiveness was positively related
      to the child's adjustment at school (i.e. achievement and social adaptation),
      while the same factor was negatively related to school aggression (bullying and
      disrupting behaviour). Overprotective mothering was associated with high degrees
      of victimization experienced by the child, whereas maternal depressiveness was
      related to both victimization and bullying behaviour on the part of the child.
      CONCLUSIONS: Parents should be included in the design of intervention plans
      aiming at the elimination of bullying at school.

PMID- 17535517
TI  - Teachers' reporting of behavioural problems and cognitive-academic performances
      in children aged 5-7 years.
AB  - BACKGROUND: The behavioural and academic performance of young children with
      teachers' reported hyperactivity, conduct problems or inattention is under
      debate. AIM: This study investigates the associations between teachers' reported
      behavioural difficulties and academic and cognitive performances in two large
      samples of preschool and school children in France. SAMPLES AND METHOD:
      Behavioural data relating to two large samples of preschool (N=475) and first
      grade (N=465) children were collected from their teachers by means of a
      questionnaire. A factorial analysis of the questionnaire revealed a four-factor
      structure ('hyperactivity', 'inattention', 'conduct problems' and
      'unsociability') that was similar in both age groups. Cognitive tests were used
      for each age group. RESULTS: Teachers' reporting of 'inattention' was associated
      with significantly lower performances in all tests in both the preschool and
      first grade samples. 'Hyperactivity' or 'conduct problems' were not consistently
      associated with the test results, when the effect of 'inattention' was taken into
      account. Preschool 'inattention', but not 'hyperactivity' or 'conduct/sociability
      problems', was related to poor performances at reading tasks in first grade.
      CONCLUSION: These findings question the pathological significance of teachers'
      report of 'hyperactivity' in young children without associated attention
      problems.

PMID- 17535518
TI  - What do children learn about biology from factual information? A comparison of
      interventions to improve understanding of contagious illnesses.
AB  - BACKGROUND: Children have been shown to hold misconceptions about illness, and
      previous work has indicated that their knowledge can be improved through the use
      of interventions. AIMS: This study aims to evaluate interventions based on the
      provision of factual information for improving understanding of contagious
      illness. SAMPLE: The participants were 96 children from two age groups: 7 and 11
      years. METHODS: During the pre-test, the children were asked about three
      contagious illnesses and one novel illness. There were three intervention
      conditions, differing in the level of factual information provided: explanations
      provided, no explanations provided and scientific factual style. The
      interventions were focused on contagious illnesses (cold, chickenpox). A post
      test was conducted 6 weeks later. RESULTS: Results from the pre-test show that
      the older children have more sophisticated understanding of illness than the
      younger children. Mean pre- to post-test change was calculated and analyses
      revealed that there is greater pre- to post-test change in the explanation and
      scientific fact conditions when compared with that in the no-explanation
      condition. The improvements in knowledge generalized to other contagious
      illnesses, and the older children showed more improvements than the younger
      children. CONCLUSIONS: These findings add to the literature on children's
      understanding of contagious illnesses and contribute towards discussions on the
      best approach to health education.

PMID- 17535519
TI  - The role of achievement goal orientations in students' perceptions of and
      preferences for classroom environment.
AB  - BACKGROUND: Recent research on achievement motivation has begun to examine the
      effects of environmental factors affecting students' motivational beliefs and
      goal tendencies. However, when interpreting and applying the results, individual
      factors underlying students' different perceptions of their learning environment
      are often ignored. An implicit assumption seems to be that regardless of their
      dispositional differences (e.g. motivational basis), students will experience and
      benefit from instructional practices in the same way. AIMS: This paper highlights
      the importance of students' dispositional motivational factors when examining
      differences in their perceptions of and preferences for the learning environment.
      The study builds on a conception of student motivation that emphasizes the
      interaction of individual and contextual factors. SAMPLE AND METHOD:
      Questionnaires served as self-report tools and assessed students' achievement
      goal orientations, self-esteem, causality beliefs, academic withdrawal and
      perceptions of and preferences for the learning environment. The sample consisted
      of 208 sixth grade elementary school students. RESULTS: Based on latent class
      cluster analysis and one-way analyses of variance, it was found that students'
      perceptions of and preferences for the learning environment vary depending on
      differences in students' motivational tendencies. CONCLUSIONS: Students'
      dispositional motivational characteristics should be taken into account both in
      theoretical considerations and in instructional interventions.

PMID- 17535520
TI  - Working memory as a predictor of written arithmetical skills in children: the
      importance of central executive functions.
AB  - BACKGROUND: The study was conducted in an attempt to further our understanding of
      how working memory contributes to written arithmetical skills in children. AIM:
      The aim was to pinpoint the contribution of different central executive functions
      and to examine the contribution of the two subcomponents of children's written
      arithmetical skills. SAMPLE AND METHOD: A total of 141 third- and fourth-graders
      were administered arithmetical tasks and measures of working memory, fluid IQ and
      reading. Regression analysis was used to examine the relationship between working
      memory and written arithmetical skills. RESULTS: Three central executive measures
      (counting span, trail making and verbal fluency) and one phonological loop
      measure (Digit Span) were significant and predictors of arithmetical performance
      when the influence of reading, age and IQ was controlled for in the analysis.
      CONCLUSIONS: The present findings demonstrate that working memory, in general,
      and the central executive, in particular, contribute to children's arithmetical
      skills. It was hypothesized that monitoring and coordinating multiple processes,
      and accessing arithmetical knowledge from long-term memory, are important central
      executive functions during arithmetical performance. The contribution of the
      phonological loop and the central executive (concurrent processing and storage of
      numerical information) indicates that children aged 9-10 years primarily utilize
      verbal coding strategies during written arithmetical performance.

PMID- 17535521
TI  - Changes in quality of life and psychological need satisfaction following the
      transition to secondary school.
AB  - BACKGROUND: Quality of life (QoL) is an important area for research during
      adolescence, due to its associations with (1) physical and mental health and (2)
      the emergence of health risk behaviours. A time that poses a particular threat to
      QoL is the transition from primary to secondary school. AIMS: This study aimed to
      investigate changes in QoL immediately following the transition to secondary
      school. Using Self-Determination Theory (SDT) as a conceptual foundation, the
      relationship between QoL and satisfaction of the three basic psychological needs
      advanced by SDT (autonomy, competence and relatedness) was explored. SAMPLE: The
      sample comprised 63 Year 7 students (age 11-12 years) attending a UK
      coeducational secondary school. METHOD: Data were collected using self-report
      questionnaires on three occasions over 10 weeks, starting on the second week of
      term. Change in need satisfaction was used to predict change in QoL, and the
      possible reciprocal relationship explored using regression analysis. RESULTS: A
      meaningful improvement in QoL was recorded for 21% of students. Improvements in
      QoL were predicted by satisfaction of the needs for autonomy and relatedness, but
      not by competence, explaining 36% of the variance. QoL showed a weaker, but
      reciprocal effect on need satisfaction. CONCLUSIONS: The findings suggest that
      support for the needs for autonomy and relatedness would provide the most likely
      route to the enhancement of student QoL over the transition to senior school.

PMID- 17535522
TI  - When being a girl matters less: accessibility of gender-related self-knowledge in
      single-sex and coeducational classes and its impact on students' physics-related
      self-concept of ability.
AB  - BACKGROUND: Establishing or preserving single-sex schooling has been widely
      discussed as a way of bringing more girls into the natural sciences. AIMS: We
      test the assumption that the beneficial effects of single-sex education on girls'
      self-concept of ability in masculine subjects such as physics are due to the
      lower accessibility of gender-related self-knowledge in single-sex classes.
      SAMPLE: N=401 eighth-graders (mean age 14.0 years) from coeducational
      comprehensive schools. METHODS: Random assignment of students to single-sex vs.
      coeducational physics classes throughout the eighth grade. At the end of the
      year, students' physics-related self-concept of ability was measured using a
      questionnaire. In a subsample of N=134 students, the accessibility of gender
      related self-knowledge during physics classes was assessed by measuring latencies
      and endorsement of sex-typed trait adjectives. RESULTS: Girls from single-sex
      physics classes reported a better physics-related self-concept of ability than
      girls from coeducational classes, while boys' self-concept of ability did not
      vary according to class composition. For both boys and girls, gender-related self
      knowledge was less accessible in single-sex classes than in mixed-sex classes. To
      the extent that girls' feminine self-knowledge was relatively less accessible
      than their masculine self-knowledge, their physics-related self-concept of
      ability improved at the end of the school year. CONCLUSIONS: By revealing the
      importance of the differential accessibility of gender-related self-knowledge in
      single- and mixed-sex settings, our study clarifies why single-sex schooling
      helps adolescents to gain a better self-concept of ability in school subjects
      that are considered inappropriate for their own sex.

PMID- 17535523
TI  - The structure of PTSD symptoms: a test of alternative models using confirmatory
      factor analysis.
AB  - OBJECTIVES: This study aimed to examine the structure of self-reported post
      traumatic stress disorder (PTSD) symptoms. DESIGN: Based on previous factor
      analytic findings and the DSM-IV formulation, six confirmatory factor models were
      specified and estimated that reflected different symptom clusters. METHODS: The
      analyses were based on responses from 1116 participants who had suffered whiplash
      injuries and screened for full or subclinical PTSD using the Harvard Trauma
      Questionnaire. RESULTS: A correlated four-factor model with re-experiencing,
      avoidance, dysphoria and arousal factors fitted the data very well. Correlations
      with criteria measures showed that these factors were associated with other
      trauma related variables in a theoretically predictable way and showed evidence
      of unique predictive utility. CONCLUSIONS: These results concur with previous
      research findings using different trauma populations but do not reflect the
      current DSM-IV symptom groupings.

PMID- 17535525
TI  - The relationship between beliefs about depression and coping strategies: gender
      differences.
AB  - OBJECTIVE: Leventhal's common-sense model of illness representation provides a
      conceptual framework for exploring the relationship between beliefs about
      depressive illness and use of coping strategies. We explored this relationship
      among depressed patients both across genders and in terms of gender differences.
      DESIGN: Depressed primary care patients prescribed antidepressants provided self
      report measures of beliefs about depression, emotional reaction to depression,
      beliefs about medications and coping strategies used. Baseline data from a
      longitudinal study is presented. METHOD: Primary data analyses were conducted
      using canonical correlation analysis, a multivariate statistical method akin to
      principal component and regression analyses. It allows for parsimonious
      description of the association between two multivariate sets of variables (in
      this case, beliefs about depression and coping strategies) by identifying pairs
      of linear combinations that account for the majority of the between association
      from the two sets of variables. RESULTS: The sample consisted of 189 depressed
      primary care patients (70.4% female). Results indicated that emotional reaction
      to depression is a major factor in determining coping strategies. Greater
      emotional reaction to depression was associated with maladaptive coping for men
      and women, while women showed additional relationships between greater perceived
      control over depression and more adaptive coping techniques as well as between
      perception of consequences of depression and problem solving. CONCLUSIONS: The
      present research provides preliminary evidence that beliefs about depression are
      related to coping styles. Further, men and women may differ in the way in which
      their perceptions about depression influence coping styles adopted.

PMID- 17535526
TI  - Cognitive biases for trauma stimuli in people with schizophrenia.
AB  - OBJECTIVES: This study investigates whether cognitive biases related to trauma
      (physical and sexual trauma) are present in a sample of participants with a
      diagnosis of schizophrenia. METHOD: Fifty-three participants, with a DSM-IV
      diagnosis of schizophrenia, completed tasks of attentional and memory bias,
      followed by several trauma report questionnaires. Those who reported a history of
      sexual and/or physical trauma were compared with a 'non-specific/no-trauma'
      subgroup. The reliability of trauma reports was determined by comparing current
      data on the Trauma History Questionnaire to that gathered one year previously,
      for a subsample of participants. Concordance rates and kappa coefficients
      suggested moderate to high reliability for reports of sexual and physical trauma.
      Attentional bias was assessed by comparing colour-naming times on modified
      Stroops, of either a sexual or physical nature, with control Stroops with
      negative, positive and neutral emotionally valenced stimuli. A subsequent
      incidental recall memory task was then employed. RESULTS: High rates of sexual
      and/or physical trauma were found. Those who reported a history of sexual trauma
      evidenced a statistically significant increase in colour-naming times for sexual
      trauma stimuli, compared to both the 'physical trauma only' and the 'non
      specific/no trauma' control groups. They also showed greater incidental recall of
      sexual trauma words in comparison to the other groups. Such a pattern was not,
      however, discerned for those reporting histories of physical trauma. CONCLUSIONS:
      Findings suggest cognitive schemata related to sexual trauma remains 'active' in
      those people with schizophrenia who report a related history.

PMID- 17535527
TI  - Emotion identification and tension in female patients with borderline personality
      disorder.
AB  - OBJECTIVES: This study investigates the identification of emotions in patients
      with borderline personality disorder (BPD), when compared with mentally healthy
      control subjects. The inability to identify different emotions is considered as
      an essential component of affect dysregulation in BPD that has rarely been
      empirically investigated. METHODS: In this study, 30 female borderline patients
      and 28 healthy control participants received a handheld-PC for a 24-hour period
      that reminded them hourly to enter data. RESULTS: When compared with the control
      group, patients showed pronounced difficulties in emotion identification.
      Moreover, the data revealed a significant relationship between difficulties in
      identifying emotions and levels of aversive inner tension for BPD patients, but
      not for control subjects. CONCLUSIONS: Results indicate that the inability to
      identify different emotions is a problem that characterizes borderline patients
      in real-life situations. Treatment programs should, therefore, focus on the
      improvement of emotion identification and regulation.

PMID- 17535528
TI  - Intact Wisconsin Card Sorting Test performance: implications for the role of
      executive function in schizophrenia.
AB  - OBJECTIVES: The present study sought to examine patients with schizophrenia who
      are able to perform adequately on the Wisconsin Card Sorting Test (WCST), which
      is a test that is usually challenging for individuals with schizophrenia due to
      common problems in executive function. METHOD AND DESIGN: Patients' WCST
      performance was classified as either 'intact' (fewer than 15% perseverative
      errors) or 'impaired' (15% or greater). Individuals with intact performance
      (N=61; 36.3%) and impaired performance (N=107; 63.7%) were then compared on
      several clinical and socio-demographic variables in order to determine how those
      with intact executive function differed from those with impaired executive
      function as measured by the WCST. RESULTS: Patients with intact performance were
      more similar than different from patients with impaired performance. Only
      negative symptoms as assessed by Andreasen's Scale for the Assessment of Negative
      Symptoms (SANS) and Hamilton Depression Rating Scale (HDRS) scores were found to
      differ significantly between these two groups while the Global Assessment of
      Functioning Scale (GAF), and positive symptom scores as assessed by Andreasen's
      Scale for the Assessment of Positive Symptoms (SAPS) approached significance.
      Patients with schizophrenia with intact WCST performance had a lower mean
      negative symptom score and a lower mean HDRS score than patients with
      schizophrenia with impaired WCST performance. The two groups were alike with
      respect to Beck Depression Inventory (BDI) scores, age at first hospitalization,
      mean number of previous hospitalizations and their families' years of education.
      A binary logistic regression indicated that differences between the group of
      individuals with intact performance and the group of individuals with impaired
      performance were attributable to full-scale IQ. CONCLUSIONS: Those with 'intact'
      WCST performance exhibited fewer negative symptoms and had lower HDRS scores than
      those with 'impaired' performance, but both differences were attributable to full
      scale IQ based on a binary logistic regression. It is this latter finding that is
      considered to be the most salient finding of this paper.

PMID- 17535529
TI  - Caring for people with eating disorders: factors associated with psychological
      distress and negative caregiving appraisals in carers of people with eating
      disorders.
AB  - OBJECTIVES: Carers of people with eating disorders (ED) have high levels of
      distress, but little is known about the contributing factors. The aim of this
      study was to examine predictors of carers' distress and caregiving appraisals
      using a model of caregiving adapted from the previous literature. DESIGN: A cross
      sectional design was used. METHODS: A sample of 115 individuals currently caring
      for someone with an ED participated in the study. Carers completed self-report
      assessments of psychological distress (GHQ-12; Goldberg & Williams, 1988),
      experience of caregiving (Szmukler et al., 1996), illness representations (IPQ
      SCV; Barrowclough, Lobban, Hatton, & Quinn, 2001) and caregiving needs (CaNAM;
      Haigh & Treasure, 2003). Simple and multiple hierarchical regressions were
      conducted. RESULTS: Approximately 36% (39/109) of carers had scores on the GHQ
      which indicated mental health difficulties, with 17% (19/109) experiencing high
      psychological distress. A negative experience of caregiving was associated with
      carers' distress. The dependency of the individual with the ED and stigma
      associated with the illness were most highly predictive of carers' distress.
      Shorter illness duration, higher levels of needs (lower levels of support) and
      perceptions of high illness consequences contributed to greater negative
      caregiving appraisals. The belief that the illness was attributable to the
      sufferers' personality was related to fewer positive appraisals. CONCLUSIONS:
      Adjusting to the impact of a family member experiencing an ED is problematic, as
      suggested by the relationship between shorter illness duration and greater
      negative appraisals of caregiving. Interventions to help reduce dependency and
      alleviate stigma may help to decrease carers' distress.

PMID- 17535530
TI  - The impact of mood induction on the accessibility of positive and negative future
      events in a group of dysphoric adolescent in-patients.
AB  - OBJECTIVE: This study aimed at experimentally affecting the fluency with which
      positive and negative future events are generated by depressive adolescents.
      METHOD: Adolescent in-patients with elevated depression were randomized into a
      positive or negative mood induction condition (N=24 in each group) and then
      presented with the Future Thinking Task asking participants to generate as many
      future events of a specified valence as possible. RESULTS: The inductions
      resulted in significant mood differences between groups. The assumed interaction
      between mood condition and reported positive and negative future events was
      confirmed. Particularly, the generation of negative future event representations
      differed between the mood induction groups. CONCLUSIONS: Dysphoric adolescents
      given a negative mood induction differ from those given a positive mood induction
      in their ability to think of future positive and negative events that they might
      experience.

PMID- 17535531
TI  - Is performance on the Wechsler test of adult reading affected by traumatic brain
      injury?
AB  - OBJECTIVES: The validity of the National Adult Reading Test (NART) as a predictor
      of premorbid IQ when used with patients who have sustained a traumatic brain
      injury (TBI) has been questioned in recent years. This study examined whether
      performance on the Wechsler Test of Adult Reading (WTAR) is similarly affected by
      TBI in the first year after an injury. DESIGN AND METHOD: The WTAR scores of
      participants who had sustained a mild TBI (N=82), moderate TBI (N=73), severe TBI
      (N=61) or an orthopaedic injury (N=95) were compared (cross-sectional study). A
      subset of 21 mild TBI, 31 moderate TBI, 26 severe TBI and 21 control group
      participants were additionally reassessed 6 months later to assess the impact of
      recovery on WTAR scores (longitudinal study). RESULTS: The severe TBI group had
      significantly lower scores on the WTAR than the mild TBI, moderate TBI and
      control groups in the cross-sectional study, despite being matched
      demographically. The findings from the longitudinal study revealed a significant
      group difference and a small improvement in performance over time but the
      interaction between group and time was not significant, suggesting that the
      improvements in WTAR performance over time were not restricted to more severely
      injured individuals whose performance was temporarily suppressed. CONCLUSIONS:
      These findings suggest that reading performance may be affected by severe TBI and
      that the WTAR may underestimate premorbid IQ when used in this context, which may
      cause clinicians to underestimate the cognitive deficits experienced by these
      patients.

PMID- 17535532
TI  - Operationalizing cognitive vulnerability and stress from the perspective of the
      hopelessness theory: a multi-wave longitudinal study of children of affectively
      ill parents.
AB  - OBJECTIVES: The current study tested the diathesis-stress component of the
      hopelessness theory (HT) in a sample of youth using (1) a weakest link approach
      towards operationalizing cognitive vulnerability (e.g. a child's degree of
      vulnerability is determined by his/her most depressogenic inferential style; DIS)
      and (2) an idiographic approach towards operationalizing high stress (e.g. high
      stress is when a child is experiencing a level of stress that is higher than
      his/her own average level of stress). We also examined whether the association
      between within-subject fluctuations in hassles and depressive symptoms in
      cognitively vulnerable youth was moderated by absolute stress levels (the between
      subject effect of stress). DESIGN: A multi-wave longitudinal design was used to
      examine whether the association between within-subject fluctuations in hassles
      and depressive symptoms was moderated by a depressogenic weakest link. METHODS:
      At Time 1, 140 children (between 6 and 14 years of age) of parents with a history
      of major depressive episodes completed measures assessing DISs and depressive
      symptoms. Every 6 weeks, for the subsequent year, children completed measures
      assessing depressive symptoms and hassles. RESULTS: The results of hierarchical
      linear modelling analyses indicated that a depressogenic weakest link was
      associated with greater elevations in depressive symptoms following elevations in
      hassles in girls but not in boys. CONCLUSIONS: Results provide partial support
      for the applicability of the diathesis-stress component of the HT to youth.
      Integration of the current findings with those obtained in past research
      examining the diathesis-stress component of the hopelessness theory in youth
      suggests the utilization of an idiographic approach to examining vulnerability
      stress theories may potentially lead to an increased understanding of gender
      differences in depression.

PMID- 17535533
TI  - A comparison of direct and spontaneous methods for assessing parental
      attributions.
AB  - OBJECTIVES: The study aim was to test whether spontaneous parental attributions
      were more closely related to parental attributions reported after a third child
      non-compliance, than to those reported after the first non-compliance. METHODS:
      Twenty-six parents completed two attributional measures. Direct attributions were
      measured using Dopke and Milner's procedure where a vignette describing child non
      compliance is presented three times and attributions elicited after the first and
      third non-compliance. Spontaneous attributions were elicited during interview and
      coded using the Leeds Attributional Coding System. RESULTS: Spontaneous
      attributions were no more associated with parental attributions after the third
      child non-compliance than with those reported after the first. CONCLUSION: The
      results suggest that the measures may be assessing different aspects of parental
      cognition.

PMID- 17535534
TI  - Correspondence between self-ratings and key-workers' ratings of depression in
      adults with mild learning disabilities.
AB  - OBJECTIVE: This study assessed the association between self-ratings and key
      worker ratings of depression in people with mild learning disabilities. METHOD:
      The Zung Depression Scale was completed by 74 adults with mild learning
      disabilities and a modified version of the questionnaire was completed by two key
      workers at two periods in time. RESULTS: The correlations between ratings of
      depression by key-workers were high and key-worker ratings correlated
      significantly with self-rating. The depression scores were found to be temporally
      stable. CONCLUSIONS: The findings suggest that proxy raters appear to be able to
      make reliable and valid judgements about other people's self-reported levels of
      depression.

PMID- 17535535
TI  - An empirical definition of clinical supervision.
AB  - OBJECTIVES: The growing recognition of clinical supervision as the basis for high
      quality mental health services is apparent in policy, research and clinical
      practice, but an empirical definition is required to progress research and
      practice. METHOD: A logical analysis was used to draft a working definition, and
      then a systematic review of 24 empirical studies of clinical supervision produced
      a best evidence synthesis, which was used to test and improve this definition.
      RESULTS: The logical analysis indicated that the most popular definition (Bernard
      & Goodyear, 1992) failed all four necessary tests of a good definition:
      precision, specification, operationalization and corroboration. The systematic
      review synthesis was then used to test the working definition, which passed these
      tests (with two amendments). CONCLUSION: These two complementary review
      approaches created a firmer basis for advancing research and practice.

PMID- 17535536
TI  - Low specificity of symptoms on the post-traumatic stress disorder (PTSD) symptom
      scale: a comparison of individuals with PTSD, individuals with other anxiety
      disorders and individuals without psychopathology.
AB  - OBJECTIVES: Screening for post-traumatic stress disorder (PTSD) takes place in
      clinical and research settings where diagnostic interviews are not feasible, and
      typically relies on self-report instruments like the PTSD symptom scale (PSS).
      Concerns have been raised about the specificity of PTSD symptoms assessed by
      questionnaires. This study examined whether the PSS distinguishes between
      patients with PTSD and those with other anxiety disorders or healthy controls.
      DESIGN: A between-participants design was employed. METHODS: The participants
      were 65 individuals with PTSD, 40 individuals with other anxiety disorders and 40
      healthy controls. They completed the PSS with respect to a range of stressful
      life-events. RESULTS: Using this instrument, 86% of individuals with PTSD and 5%
      of healthy controls endorsed sufficient symptoms to meet the PTSD diagnosis. This
      was also the case for 43% of individuals with other anxiety disorders, and self
      reported symptoms related to traumatic events and aversive events that are
      generally not considered traumatic. CONCLUSIONS: The findings suggest that many
      people screened positive for PTSD may actually be suffering from another anxiety
      disorder.

PMID- 17535537
TI  - Outcome of cognitive-behavioural therapy in training practice with anxiety
      disorder patients.
AB  - OBJECTIVES: This study aims to assess the effectiveness of cognitive-behavioural
      therapy applied by trainee therapists in patients with anxiety disorders seen in
      a private university service and to examine whether this effectiveness is
      comparable to that observed in controlled studies. DESIGN: We compared the
      effectiveness of cognitive-behavioural therapy at a private centre with that
      observed in meta-analyses and reviews of controlled studies. METHODS: Out of the
      96 initial patients with anxiety disorder, 64 completed the cognitive-behavioural
      treatment and 59 also answered a series of questionnaires pre- and post
      treatment. The effect size of the intervention was calculated, as were the
      percentages of patients who improved and those who recovered. RESULTS: The pre
      post effect size (1.09) was large, although somewhat lower than those observed in
      a meta-analysis of Spanish studies and in a range of international meta-analyses;
      moreover, twice as many hours of treatment were administered (M=27.4) and the
      drop-out rate was higher (33.3%). The percentages of patients who improved (61%)
      and those who recovered (52.5%) were roughly comparable to those reported in
      various reviews of studies performed in anxiety disorders. CONCLUSIONS: Cognitive
      behavioural therapy applied by trainee therapists in a private university service
      appears effective, although this efficacy may be somewhat lower than that in
      controlled studies. Moreover, the duration of treatment and the drop-out rate may
      be higher.

PMID- 17535539
TI  - Economic impacts attributable to the early clinical benefit of atorvastatin
      therapy--a US managed care perspective.
AB  - OBJECTIVE: The clinical literature suggests that atorvastatin therapy achieves a
      reduction in major cardiovascular events within the first year of therapy. Aside
      from obvious clinical benefits, economic advantage may also result from this
      observation. The present analysis modeled the clinical and economic consequences
      of initiating atorvastatin versus generic simvastatin in defined US managed care
      organization patient populations. RESEARCH DESIGN AND METHODS: A cost-consequence
      model was developed to estimate the differential rate and associated costs of
      cardiovascular events occurring over 2 years using real world price and adherence
      data. Four defined patient populations were included from representative
      atorvastatin trials: (1) diabetes mellitus; (2) multiple risk factors; (3)
      coronary heart disease; and (4) acute coronary syndrome. Costs of care included
      drug costs and costs of managing cardiovascular events. Univariate sensitivity
      analyses and multivariate sensitivity analysis via Monte Carlo simulation were
      conducted to test the robustness of the results. MAIN OUTCOME MEASURES: The
      number of cardiovascular events avoided per 100,000 patients initiated on
      atorvastatin as compared with simvastatin, and total treatment costs. RESULTS:
      The model predicts that, relative to simvastatin, atorvastatin will prevent 941
      (95% confidence interval [CI] 481-1367) cardiovascular events after 1 year and
      1426 (95% CI 833-1987) events after 2 years, per 100,000 patients. This is
      expected to reduce the cost of cardiovascular events by $365 (95% CI $192-$527)
      and $552 (95% CI $327-$763) per patient (US$ 2006), respectively, offsetting 80%
      and 75% of the medication cost difference between atorvastatin and simvastatin
      after 1 and 2 years, respectively. The incremental costs associated with
      atorvastatin treatment were estimated at $94 (95% CI -$68 to $267) and $175 (95%
      CI -$37 to $399) per patient after 1 and 2 years, respectively. Results were
      sensitive to assumptions regarding simvastatin efficacy and drug acquisition
      costs. CONCLUSIONS: Although the present analysis is based in part on indirect
      comparisons and on trials not designed or statistically powered to specifically
      test the early benefits hypothesis, it suggests that atorvastatin's assumed early
      reduction of cardiovascular events partly offsets the acquisition price
      difference between atorvastatin and generic simvastatin in various groups of high
      risk patients newly initiated on statin treatment.

PMID- 17535540
TI  - An exploratory study of the needs of staff who care for offenders with a
      diagnosis of personality disorder.
AB  - People with a diagnosis of personality disorder who are considered a risk to
      others are a current concern for public services, government and society.
      Healthcare provision for this group has recently increased, making it important
      to begin to learn about the needs of staff working in such a challenging area. An
      exploratory interview study with staff working in a medium secure unit for
      offenders with a diagnosis of personality disorder (Unit Z) is presented.
      Interviews were line-coded and analysed according to the grounded theory method.
      A model was developed from higher order categories. This related key contextual
      factors to areas of concern for staff. The key contextual factors were:
      'complexity of the task' and 'tension in the relationship with outside'. The
      areas of concern were: 'desire for more meaningful contact', 'contradictory
      attitude towards openness', 'feeling physically safe but emotionally vulnerable',
      'ambivalence towards structure and control' and 'emphasis on staff
      relationships'. 'Risk of isolation' formed a core category and described Unit Z
      staff's pervading sense of distance from the outside world. These categories are
      described with supporting quotations and discussed in relation to the existing
      literature. Their implications for clinical practice and the development of
      services are considered.

PMID- 17535541
TI  - Exploring the meaning of separation in second-generation young South Asian women
      in Britain.
AB  - OBJECTIVES: To explore the experiences of young second-generation South Asian
      women living in Britain; to try and understand their experiences, deconstruct the
      term cultural conflict and understand it within a psychological framework. In
      particular, the aim was to explore issues of separation and individuation, and
      the meanings attributed to these concepts. DESIGN: An interview-based study using
      Interpretative Phenomenological Analysis to analyse the data. METHODS: Interviews
      were conducted with six second-generation South Asian women aged 16-20, who had
      no prior contact with mental health services. RESULTS: Five main themes were
      identified from the analysis: differences in the meaning of adulthood, community
      policing, pressures and stressors, protective factors/coping and barriers to
      coping. CONCLUSIONS: The participants' perceived differences in the meaning of
      adulthood in Asian cultures in comparison with Western cultures. These
      differences, in conjunction with the community policing that they were exposed
      to, contributed to the pressures and stressors - in particular lack of control
      and a desire to make individual decisions. The results indicated that the
      differences in the meaning of adulthood in a collective culture challenged the
      assumptions of the separation-individuation model, and was a key element in
      cultural conflict. This highlighted the complexities of generalizing research
      findings across all social groups, and questioned the validity of applying
      existing psychological theory to this population. The clinical implications of
      coping/protective factors and barriers to coping were discussed.

PMID- 17535542
TI  - An integrative complexity analysis of cognitive behaviour therapy sessions for
      borderline personality disorder.
AB  - OBJECTIVES: Integrative complexity (IC), a measure of cognitive style, was used
      to analyse discourse in Cognitive Behaviour Therapy (CBT) sessions from patients
      with borderline personality disorder treated in the BOSCOT trial. It was
      predicted that patients' level of integrative complexity would be positively
      associated with the outcome of therapy. That is, an increase in patients' level
      of integrative complexity would be associated with good outcome. We also
      predicted that therapists would also show an increase in the level of complexity
      associated with their patient's increase in integrative complexity and good
      outcome. DESIGN: Ten patients who received CBT were categorized according to the
      outcome, good (N=5) and poor (N=5), using an algorithm that incorporated the
      number of suicide attempts and magnitude of change in severity of depression
      during therapy. METHOD: For each patient and their therapist, an early and a late
      therapy session were transcribed and coded for integrative complexity (IC) (N=20
      sessions transcribed). IC scores for patients and therapists were compared across
      early and late therapy sessions and for good and poor outcomes of therapy.
      RESULTS: The majority of discourse was at the lower levels of IC. Higher levels
      of IC at baseline were related to depression and anxiety. Good outcome was not
      associated with a change in the level of IC between earlier and later CBT
      sessions. Therapists, however, showed an increase in IC when patient's outcome
      was poor. In addition, an increase in patient's IC was associated with
      improvement in social functioning. CONCLUSIONS: Therapists may overcompensate for
      patient's poor outcome by giving more complex explanations to patients. Higher
      complexity does not necessarily lead to better outcomes.

PMID- 17535543
TI  - Do clinical researchers believe they should be clinically active? A survey in the
      United States and the United Kingdom.
AB  - Do clinical researchers believe they should be clinically active? In an on-line
      survey among 64 senior researchers from the United States (59%) and the United
      Kingdom (41%), there was a strong consensus that clinical practice is desirable,
      especially for psychotherapy researchers, but not absolutely necessary. The
      researchers were uniformly opposed to the idea that researchers should be
      required by professional organizations to engage in clinical practice. Four
      advantages of clinical involvement were identified: (1) it experientially grounds
      researchers in the complexities of clinical reality; (2) it inspires ideas and
      helps generate hypotheses; (3) it enables researchers to test the practical
      applicability of research-based models and interventions and (4) it enhances
      public credibility and confirms one's identity as a clinical psychologist.
      However, these benefits were balanced by two salient costs: (1) clinical work is
      associated with intensive time demands and can therefore potentially interfere
      with research productivity and (2) exposure to a small number of vivid but
      unrepresentative clinical cases can cloud one's judgment and interfere with
      scientific objectivity. The potential of these findings to improve the strained
      relationship between clinical researchers and practitioners is discussed.

PMID- 17535545
TI  - Kant, cognitive psychotherapy, and the hardening of the categories.
AB  - Contemporary models of psychotherapy owe a considerable intellectual debt to
      philosophy, even though the contributions of philosophers to contemporary
      practice in the field often go unrecognized. A case in point is Kant's
      epistemology, which is foundational to cognitive approaches to psychotherapy.
      Here, it is argued that the rigid use of certain judgments represented in Kant's
      conceptual scheme underlies patterns of distorted or dysfunctional thinking
      associated with emotional disorders. Kantian judgments of necessity, disjunction,
      particularity and universality have counterpoints in contemporary conceptions of
      cognitive distortions. Moreover, Kantian epistemology has important therapeutic
      implications with respect to helping people with emotional disorders recognize
      and challenge rigidly held judgments or categories of understanding. The Kantian
      perspective also leads us to consider the cognitive frameworks or thought
      structures that underlie dysfunctional thinking patterns.

PMID- 17535544
TI  - Attachment styles, earlier interpersonal relationships and schizotypy in a non
      clinical sample.
AB  - OBJECTIVES: This paper investigates associations between adult attachment style,
      relationships with significant others during childhood, traumatic life-events and
      schizotypy. DESIGN: Relationships between attachment and hypothesized correlates
      were investigated in a cross-sectional design using an analogue sample. The
      reliability of the attachment and trauma measures was investigated using a test
      retest design. METHODS: Three hundred and four students completed the self-report
      version of the Psychosis Attachment Measure (PAM), maternal and paternal versions
      of the Parental Bonding Instrument, the Attachment History Questionnaire, a
      measure of trauma and the Oxford-Liverpool Inventory of Feelings and Experiences
      scale through an internet website. RESULTS: As predicted, there were
      statistically significant associations between insecure attachment in adult
      relationships and experiences of negative interpersonal events. Both earlier
      interpersonal experiences and adult attachment style predicted schizotypy, and
      adult attachment style emerged as an independent predictor of positive
      schizotypal characteristics. CONCLUSIONS: The findings support associations
      between adult attachment style and previous interpersonal experiences and between
      adult attachment and schizotypy. The PAM is a reliable and valid instrument that
      can be used to explore attachment styles in analogue samples and associations
      between attachment styles and psychotic symptoms in clinical samples.

PMID- 17535546
TI  - Predictors of change in music therapy with children and adolescents: the role of
      therapeutic techniques.
AB  - Music therapy has been shown to be efficacious in experimental studies. However,
      there is little empirical research knowledge about what elements of music therapy
      influence its effectiveness in clinical practice. Children and adolescents with
      psychopathology (N=75) were assessed before and after participating in individual
      music therapy with 1 out of 15 music therapists in the Vienna region.
      Relationships between outcomes (as evaluated by parents) and therapy contents (as
      reported by therapists) were examined using general linear modelling. Results
      indicated that clients' symptoms and burdens on their social environment showed
      greater improvement when music therapy was limited to discipline-specific music
      therapy techniques and did not include other media such as play therapy elements.
      The findings indicate the importance of being aware of a therapy method's
      specific strengths and limitations. More research on the indicated specific
      ingredients of music therapy intervention is needed.

PMID- 17535547
TI  - Differences in clinical characteristics between patients assessed for NHS
      specialist psychotherapy and primary care counselling.
AB  - OBJECTIVES: Although several studies have described patient populations in
      primary care counselling settings and NHS (National Health Service) specialist
      psychotherapy settings, there is a paucity of studies specifically comparing
      differences in clinical characteristics between the two groups of patients. The
      aim of this study is to ascertain if specialist psychotherapy referrals represent
      a more challenging client group than primary care counselling patients. DESIGN:
      We compare the socio-demographic features and severity of presentation in the
      symptomatic, interpersonal problems and global adjustment dimensions of a sample
      of patients (N=384) assessed by a primary care counselling service located in
      North London and a sample of patients (N=853) assessed in eight NHS psychotherapy
      centres located within urban settings in England. METHODS: Both the groups
      completed the Brief Symptom Inventory, the Inventory of Interpersonal Problems
      and Clinical Outcomes in Routine Evaluation Outcome Measure. RESULTS: Patients
      referred for specialist psychotherapy services were more dysfunctional than those
      referred for primary care counselling. The linear function constructed to
      discriminate the groups showed that a combination of more psychotic symptoms,
      social inhibitions and higher risk of self-harm effectively identified those
      referred to psychotherapy services, while patients exhibiting greater levels of
      somatic and anxiety symptoms and non-assertiveness were more likely to be seen in
      primary care settings. However, similarities between the two samples were also
      marked, as shown by the overlap in the distribution of clinical outcomes in
      routine evaluation clinical scores in the two samples. CONCLUSIONS: The findings
      are discussed in terms of their implications for policy and service delivery of
      these two types of psychological therapy services.

PMID- 17535548
TI  - I was being myself but being an actor too: the experience of a Black male in
      interracial psychotherapy.
AB  - In recent years, investigators have indicated that the psychotherapy process is
      of considerable importance in the context of interracial psychotherapy. Despite
      the interest in the area, minimal research has examined how racial difference
      impacts the psychotherapy process. This study examines the lived experience of
      interracial psychodynamic psychotherapy via an in-depth interview with an African
      American man who had been in therapy with a European American therapist. This
      qualitative study utilizes a hermeneutic phenomenological approach, which accepts
      that understanding is contingent on both sociohistorical situatedness and
      relational dynamics. The study participant was chosen because of his interest in
      the area and willingness to explore it in detail with the interviewer. A number
      of themes emerged, the most salient of which are the multidimensionality of the
      experience and the 'absent presence' of race in the therapy process. This
      client's experience was both positive and negative, and in many cases, the same
      process-related variables contributed both positively and negatively to the
      client's therapeutic experience. Issues of trust, perceived cultural issues and
      therapy focus contributed to and detracted from the therapy experience. The depth
      of the therapy experience was limited by the therapist not explicitly addressing
      race.

PMID- 17535549
TI  - p53, BCL-2 and BAX in non-small cell lung cancer brain metastases: a comparison
      of real-time RT-PCR, ELISA and immunohistochemical techniques.
AB  - OBJECTIVES: Metastasis to the brain is a severe and common complication in non
      small cell lung cancer (NSCLC). The examination of cell cycle associated genes in
      these lesions may contribute to the understanding of metastatic growths in the
      central nervous system. The aim of this study was to evaluate the p53, BCL-2 and
      BAX mRNA and protein expression in NSCLC brain metastases in comparison with
      matched primary tumors. METHODS: For quantitative TaqMan real-time reverse
      transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent
      assay (ELISA), fresh frozen tumor specimens from 12 patients with NSCLC brain
      metastases were available. For immunohistochemical staining, 78 surgically
      removed NSCLC brain metastases were used. PCR results were analysed using the
      DeltaDeltaCT method. Staining was analysed using a modified immunoreactive score
      (IRS). RESULTS: Overall, p53, BCL-2 and BAX expression values in brain metastases
      and primary tumors showed a wide variety. The comparison of different techniques
      revealed different findings on the mRNA and protein level. Herein, PCR and ELISA
      revealed no clear tendencies. In contrast, immunohistochemistry showed
      significant overexpression of BAX and underexpression of BCL-2 in brain
      metastases. CONCLUSION: A high variability in the expression of p53, BCL-2 and
      BAX in NSCLC exists in brain metastases. Immunohistochemistry revealed
      overexpression of BAX and underexpression of BCL-2 in brain metastases, whereas
      there were no clear tendencies using PCR and ELISA techniques. More insights into
      the BAX/BCL-2 interaction are needed before reasonable conclusions can be drawn
      from the existing data.

PMID- 17535550
TI  - Correlation between distal motor latency and compound muscle action potential in
      amyotrophic lateral sclerosis.
AB  - OBJECTIVES: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative
      disorder, characterized by a selective progressive degeneration of the motor
      system. Electromyography is essential for the diagnosis of ALS. The measurement
      of motor conduction of peripheral nerves is of major importance to recognize
      other possible causes of progressive muscle wasting. However, there are also
      pathologic changes in nerve conduction studies in ALS patients. METHODS: In this
      study we analysed the values of distal motor latency (DML), compound muscle
      action potential (CMAP) and motor nerve conduction velocity (MNCV) in 95 patients
      with definite ALS. RESULTS: We found slight slowing of MNCV and moderate to
      strong reduction of CMAP and a prolongation of DML. We found no significant
      correlation between MNCV and CMAP. DISCUSSION: The main finding of the present
      work was the negative correlation between DML and CMAP. It is interpreted as a
      very distal axonal damage as the main reason for prolongation of DML in ALS
      patients.

PMID- 17535551
TI  - Histologic and transcriptional assessment of a mild SMA model.
AB  - Spinal muscular atrophy (SMA) is caused by survival of motor neuron (SMN)
      deficiency, leading to specific motor neuron attrition. The time course and
      molecular pathophysiologic etiology of motor neuron loss observed in SMA remains
      obscure. Mice heterozygous for Smn show up to 50% motor neuron attrition by 6
      months of age and are used as a model for mild SMA in humans. To determine both
      the rate of cellular loss and the molecular events underlying motor neuron
      degeneration in SMA, motor neuron counts and mRNA quantification were performed
      in spinal cords of Smn(+/-) mice and wild-type littermates. Surprisingly, despite
      the chronic, subclinical nature of motor neuron loss, we find that the bulk of
      the loss occurs by 5 weeks of age. RNA isolated from the spinal cords of 5 week
      old Smn(+/-) mice subjected to microarray analysis reveal alterations in genes
      involved in RNA metabolism, apoptosis and transcriptional regulation including a
      general perturbation of transcripts coding for calcium binding proteins. A subset
      of these changes in expression was further characterized by semi-quantitative RT
      PCR and Western blot analysis at various time points. Taken together, these
      results indicate that spinal cord cells present the first signs of the apoptotic
      process consistent with a response to the stress of Smn depletion. A picture of
      comparatively rapid neuronal attrition in spite of the very mild nature of SMA is
      obtained. Furthermore, changes occur, which may be reactive to and not causative
      of the cellular loss, involving central cellular functions as well as calcium
      modulating proteins.

PMID- 17535552
TI  - Parvalbumin immunoreactivity and protein content alter in the hippocampus after
      adrenalectomy in seizure sensitive gerbils.
AB  - OBJECTIVES: Neurons containing parvalbumin (PV), a calcium-binding protein, in
      the hippocampus, play an important role in hippocampal excitability in epilepsy.
      In this study, we examined temporal and spatial changes of PV immunoreactivity
      and protein content in the hippocampus after adrenalectomy (ADX) in seizure
      sensitive (SS) gerbils, which are hereditarily seizure-prone. METHODS: PV
      distribution and change in SS gerbils after ADX were examined in the hippocampal
      CA1 region and in the dentate gyrus (DG) using immunohistochemistry and Western
      blot analysis. RESULTS: PV immunoreactivity in sham-operated SS gerbils was
      detected in many CA1 pyramidal cells. Three hours after ADX, PV immunoreactivity
      significantly decreased in CA1 pyramidal cells and thereafter PV immunoreactivity
      began to increase by 4 days after ADX. Four days after ADX, PV immunoreactivity
      was significantly higher than that in the sham-operated SS gerbils. In the DG of
      sham-operated SS gerbils, PV immunoreactivity was mainly detected in polymorphic
      cells. Three hours after ADX, PV immunoreactivity in the DG significantly
      decreased in the polymorphic layer. Thereafter, PV-immunoreactive neurons
      decreased with time after ADX. Western blot analysis showed that change in PV
      protein content was similar to immunohistochemical data after ADX in SS gerbils.
      CONCLUSION: Our results indicate that PV is changed in hippocampus after ADX and
      PV may be associated with the regulation of seizure activity.

PMID- 17535553
TI  - Laminin receptor 1: a novel protein interacting with human circadian clock
      protein, hPer1.
AB  - The circadian clock is the central timing system that controls numerous
      physiologic processes. The current model of these oscillators is based on
      autoregulatory transcription and translation feedback loops of these circadian
      genes in which Period1 (Per1) gene occupies a central position. The laminin
      receptor 1 (Lamr1) and its precursor are expressed in most tissues and play
      important roles in several physiologic and pathologic processes, including cell
      differentiation, growth, migration and cancer invasion. The present study showed
      that Lamr1 was a novel protein that interacted with human circadian clock protein
      hPer1 by the yeast two-hybrid system and co-immunoprecipitation, which was
      expressed in many tissues and did not display circadian rhythm. The expression of
      hPer1 was knocked down to 84.9% by the hPer1 RNA interfering test, but the
      expression levels of Lamr1 was not depressed by the hPer1 RNA interfering test.
      The results suggest that Lamr1 is a novel protein that interacts with human
      circadian clock protein hPer1 and Lamr1 is not a direct efferent element of
      circadian clock.

PMID- 17535554
TI  - Discrepancy between theoretical knowledge and real action in acute stroke: self
      assessment as an important predictor of time to admission.
AB  - BACKGROUND: Poor knowledge of stroke symptoms within the general population might
      be responsible for significant delay between symptom onset and hospital admission
      in most stroke patients. METHODS: We prospectively evaluated whether theoretical
      knowledge about stroke influenced time to admission among 102 consecutive acute
      stroke patients using standardized questionnaires. We assessed in multiple
      logistic regression models the influence of theoretical knowledge (knowledge
      about stroke symptoms and knowledge about the appropriate actions to be taken in
      the case of a stroke) on the real actions taken in the acute situation.
      Predictors of a delayed hospital admission greater than 2 hours after stroke
      onset were determined. Models were adjusted for age, gender, level of education,
      stroke severity, previous history of stroke or transient ischemic attack (TIA),
      and being alone at symptom onset. RESULTS: Patients arrived significantly later,
      if the patients themselves were the managers of the emergency situation [odds
      ratio (OR): 4.7; 95% confidence interval (CI): 1.5-140.8]. Symptom knowledge and
      action knowledge were not found to be significantly associated with shorter pre
      hospital times, whereas the correct diagnosis of stroke by the manager (OR: 0.2;
      95% CI: 0.1-0.4) and calling the emergency medical system (OR: 0.3; 95% CI: 0.1
      0.7) independently led to a higher likelihood to arrive at a hospital within 2
      hours. CONCLUSION: Our study underscores that good theoretical knowledge about
      stroke does not imply appropriate management in the emergency situation.
      Educational efforts need to incorporate more practical aspects in order to
      translate theoretical knowledge into concrete action.

PMID- 17535555
TI  - Side of the stimulated ear influences the hemispheric balance in coding tonal
      stimuli.
AB  - OBJECTIVE: To evaluate whether the side of stimulated ear affects the hemispheric
      asymmetry of auditory evoked cortical activations. METHODS: Using a whole-head
      neuromagnetometer, we recorded neuromagnetic approximately 100 ms responses
      (N100m) in 21 healthy right-handers to 100 ms 1 kHz tones delivered alternatively
      to left and right ear. RESULTS: Although the peak latencies of N100m were shorter
      in contralateral than in ipsilateral hemisphere, the difference was significant
      only for the left ear stimulation. Based on the relative N100m amplitudes across
      hemispheres, the laterality evaluation showed a rightward predominance of N100m
      activation to tone stimuli, but the lateralization toward the right hemisphere
      was more apparent by the left than by the right ear stimulation (laterality
      index: -0.27 versus -0.10, p=0.008). Within the right hemisphere, the N100m was 2
      4 mm more posterior for left ear than for right ear stimulation. CONCLUSIONS: The
      hemispheric asymmetry in auditory processing depends on the side of the
      stimulated ear. The more anterior localization of right N100m responses to
      ipsilateral than to contralateral ear stimulation suggests that there might be
      differential neuronal populations in the right hemisphere for processing
      spatially different auditory inputs.

PMID- 17535556
TI  - Remote cerebellar hemorrhage after supratentorial unruptured aneurysmal surgery:
      report of three cases.
AB  - We report three cases of remote cerebellar hemorrhage that developed after
      supratentorial unruptured aneurysmal surgery. In all cases, digital subtraction
      angiography was performed before each operation in order to rule out other
      vascular abnormalities, especially around the operative field or the posterior
      circulation. In addition, all patients were screened for any previous history of
      bleeding tendencies or other related medical disorders. Each patient underwent
      clipping surgery via the pterional approach. Remote cerebellar hemorrhage was
      identified on post-operative computed tomographic scans. In all cases, there was
      no evidence of significant associated long-term morbidity. A consideration of the
      possible pathophysiologic mechanisms underlying these post-operative remote
      cerebellar hemorrhages and suggested strategies for avoiding such complications
      are discussed.

PMID- 17535557
TI  - Spatial variations in wall thickness, material stiffness and initial shape affect
      wall stress and shape of intracranial aneurysms.
AB  - OBJECTIVE: Saccular aneurysm (sac-like ballooning) is the common form of aneurysm
      in cerebral arteries. Significant variations exist in the shape, wall thickness
      and material properties of saccular aneurysms. Aneurysms with irregular shapes
      are prone to rupture, but the underlying reason is poorly understood. The
      objective of this study was to examine the effect of spatial variations in wall
      thickness, material stiffness and initial shape on the shape and wall stress
      distribution in model aneurysms. METHODS: The stress and deformation were
      determined using non-linear finite element analysis in aneurysm models. RESULTS:
      Our results showed that local variations in wall thickness and material stiffness
      led to local stress concentrations and changes to aneurysm shape, and could cause
      'bleb' and even a multilobular appearance to the aneurysms. Initial lesion shape
      also played a significant role in determining the shape of the aneurysms.
      DISCUSSION: This study demonstrated that spatial variations in wall thickness and
      material stiffness lead to wall stress concentration in the aneurysm wall and
      affect the shape of the aneurysms. The stress concentration in the 'bleb' region
      and in the multilobular aneurysms may explain the observation that irregular
      shaped and multilobular shaped aneurysms are susceptible to bleeding and rupture.

PMID- 17535558
TI  - The pre-treatment effect on brain injury during restoration of normal perfusion
      pressure with hemodilution in a new rat model of chronic cerebral hypoperfusion.
AB  - OBJECTIVES: To investigate the effect of hemodilution with high-concentration
      human serum albumin (HSA) on brain injury in a rat model of chronic cerebral
      hypoperfusion associated with arteriovenous malformations. METHODS: The animal
      model was established by creating a fistula through an end-to-side anastomosis
      between the right distal external jugular vein and the ipsilateral common carotid
      artery, followed by ligation of the left vein draining the transverse sinus and
      bilateral external carotid arteries. The agent (20% HSA) or control solution
      (0.9% sodium chloride) was administered intravenously at a dosage of 1% body
      weight 24 hours before ligation of the fistula. Blood-brain barrier (BBB)
      disruption was judged by extravasation of Evans blue (EB) dye. EB, water content
      and the changes of myeloperoxidase (MPO) activity and superoxide dismutase (SOD)
      activity in rat brains 24 hours after ligation of the fistula were determined.
      RESULTS: EB and water content in rat brains of the pre-treated group were
      significantly decreased compared with the control group accompanied by reduction
      of MPO activity and enhancement of SOD activity. DISCUSSION: Hemodilution with
      high-concentration HSA has a certain pre-treatment effect on brain injury after
      ligation of the fistula in rat model of chronic cerebral hypoperfusion, which may
      be resulted from improved microcirculation, decrease in inflammatory cell
      infiltration and inactivation of oxygen free radicals.

PMID- 17535559
TI  - Heterogeneous regional and temporal energetic impairment following controlled
      cortical impact injury in rats.
AB  - OBJECTIVES: Following traumatic brain injury metabolic stability is impaired.
      Duration and reversibility of these changes might be important to guide specific
      interventions. METHODS: To characterize temporal and regional changes in cerebral
      metabolism, 68 male Sprague-Dawley rats were subjected to a focal cortical
      contusion. Lesion progression and mitochondrial impairment were determined by
      magnetic resonance imaging (MRI) and triphenyl tetrazolium chloride (TTC)
      staining, respectively. Metabolic alterations were determined at hours 6 and 24
      and day 7 by measuring extracellular glucose, lactate and hypoxanthine levels
      with microdialysis catheters placed adjacent and distant to the contusion and by
      quantifying changes in tissue ATP, lactate and glucose using bioluminescence
      imaging. RESULTS: The cortical lesion reached its maximal extent at hour 24 and
      remained confined to the ipsilateral hemisphere. In microdialysate, at hour 6,
      extracellular hypoxanthine and lactate reached maximal values, thereafter
      hypoxanthine normalized while lactate remained increased. Extracellular glucose
      reached the highest values at hour 24 and remained elevated. Bioluminescence
      imaging revealed heterogeneous changes in areas distant to the contusion. No
      significant changes were found in ATP content. Slightly elevated tissue glucose
      until 24 hours in the ipsilateral hemisphere was observed. Following a continuous
      increase, lactate levels were the highest by 6 hours in the ipsilateral cortex
      and hippocampus. DISCUSSION: CCI is associated with disturbances in energetic
      metabolism. Metabolic perturbation is not restricted to the early phase and the
      contusional region following focal cortical contusion, but also involves
      hippocampus and primarily uninjured parts of the hemisphere.

PMID- 17535560
TI  - Allopregnanolone modulates striatal dopamingergic activity of rats under
      different gonadal hormones conditions.
AB  - OBJECTIVES: Progesterone modulates dopamine (DA) release in corpus striatum. Our
      objective was to evaluate the effect of the i.c.v injection of the neurosteroid
      allopregnanolone (ALL), a progesterone metabolite on dopaminergic activity in the
      corpus striatum of rats under different gonadal hormonal conditions. METHODS: We
      have measured the concentrations of DOPA, DA and DOPAC (main metabolite of DA) in
      the corpus striatum in estrus and diestrus rats and in ovariectomized rats
      without hormonal replacement (OVX group) and primed with estrogen and
      progesterone (OVX(i) group). Additionally, we have used the aromatic acid
      decarboxylase inhibitor NSD in order to evaluate the function of tyrosine
      hydroxylase (TH), the rate-limiting enzyme of dopamine synthesis. RESULTS: ALL
      significantly decreased the striatal concentrations of both DA and DOPAC in the
      estrus. On the other hand, ALL increased significantly the levels of DA in the
      OVX(i) group. The DOPA accumulation in OVX(i) after NSD treatment in the ALL
      treated groups was greater than in the vehicle group. However, the estrus group
      did not modify the DOPA accumulation after NSD injection. DISCUSSION: Our results
      suggest that ALL could modulate the dopaminergic transmission in the corpus
      striatum by causing changes in the activity of TH and/or in the pre- and post
      synaptic dopaminergic terminals in the corpus striatum. This neurosteroidal
      mechanism could be a new kind of neurotransmitter systems modulation accomplished
      on TH activity itself and/or on the second messengers not related to ionic
      channels. Additionally, our results reinforce the idea of a close relationship
      between the fast non-genomic mechanism of ALL and the genomic actions of estrogen
      and progesterone.

PMID- 17535561
TI  - Subcellular redistribution of calponin underlies sustained vascular contractility
      following traumatic brain injury.
AB  - OBJECTIVES: The purpose of this study was to observe temporal changes in calponin
      (Cp), a contractile protein, in response to traumatic brain injury (TBI).
      METHODS: Double immunocytochemistry in conjunction with morphometric methods was
      used to study Cp temporal migration in smooth muscle cells (SM) of reacting
      microvessels following TBI, as induced using a weight-drop, acceleration impact
      method. RESULTS: Quantification of migrated Cp in the SM wall after TBI was
      carried out on three-dimensional orthographic reconstructions of serial,
      digitally acquired images and optical densitometry. Color shifts in Cp intensity
      were measured in three arbitrary longitudinal compartments, luminal (lu), middle
      (m) and abluminal (ablu), of SM cytoplasm with respect to proximity to the
      vessel's lumen. By 24 and 48 hours after TBI, most Cp had migrated from the SM
      compartment closest to the lu to that farthest away or ablu. In addition, a
      qualitative increase in Cp was detected closest to the ablu compartment in those
      segments of the vessel severely constricted. DISCUSSION: Cp migration from
      cytoskeletal to contractile regions of SM supports its role both in the
      initiation of vessel contractility and its interaction with cytoskeletal
      structures subjacent to the cell membrane in SM's contracted state.

PMID- 17535562
TI  - Overexpression of mouse IsK protein fused to green fluorescent protein induces
      apoptosis of human astroglioma cells.
AB  - Intracellular K(+) plays an important role in controlling ion homeostasis for
      maintaining cell volume and inhibiting activity of pro-apoptotic enzymes.
      Cytoplasmic K(+) concentration is regulated by K(+) uptake via Na(+) -K(+) 
      ATPase and K(+) efflux through K(+) channels in the plasma membrane. The IsK
      (KCNE1) protein is known to co-assemble with KCNQ1 (KvLQT1) protein to form a
      K(+) channel underlying the slowly activating delayed rectifier K(+) outward
      current which delays voltage activation. In order to further study the activity
      and cellular localization of IsK protein, we constructed a C-terminal fusion of
      IsK with EGFP (enhanced green fluorescent protein). Expression of the fusion
      protein appeared as clusters located in the plasma membrane and induced
      degeneration of both transiently or stably transfected cells.

PMID- 17535563
TI  - Biopathology of the dentate-olivary complex in sudden unexplained perinatal death
      and sudden infant death syndrome related to maternal cigarette smoking.
AB  - OBJECTIVES: The present study was aimed to evaluate the possible presence of
      cytohistologic and/or biologic modifications of the human dentate-olivary complex
      in sudden unexplained perinatal and infant deaths. METHODS: We investigated the
      histologic morphology of the dentate and inferior olivary nuclei, the glial
      index, the c-fos and apoptotic immunopositivity, as well as the possible effects
      elicited by maternal cigarette smoking, in 44 cases of perinatal and infant death
      victims, aged from the 26th gestational week to 10 months of life. RESULTS: We
      observed subtle alterations of both the medullary inferior olivary nucleus and of
      the cerebellar dentate nucleus, represented by a significant increase in the
      reactive astrocyte density and in the neuronal c-fos and apoptotic expression in
      unexplained death victims, compared with age-matched controls. These alterations
      were closely related to a maternal cigarette smoking habit. DISCUSSION: We
      postulate that maternal smoking, besides inducing the previously demonstrated
      morpho-functional alterations of the autonomic central nervous system, could also
      exert an adverse influence on the dentate-olivary complex, leading to sudden
      death in vulnerable periods of perinatal development or early infancy.

PMID- 17535564
TI  - The changes in neurotrophic properties of the peripheral nerves extracts
      following blocking of BDNF activity.
AB  - OBJECTIVES: Retinal ganglion cells (RGCs) of adult rats are unable to regenerate
      their axons after optic nerve injury and soon after they enter the pathway of
      apoptosis. They may, however, survive and regenerate new axons in response to
      application of specific peripheral nerve extracts that presumably contain a range
      of neurotrophic substances. One of the recognized substances of proven
      neurotrophic activity is brain-derived neurotrophic factor (BDNF). We have
      investigated whether blocking the BDNF activity in post-microsomal fractions
      obtained from 7 day pre-degenerated peripheral nerves would affect its
      neurotrophic properties towards RGCs after optic nerve transection in adult rats.
      METHODS: Autologous connective tissue chambers sutured to the distal end of
      transected optic nerve served as active substances containers. Surviving RGCs
      were visualized using Dil. The number of myelinated outgrowing fibers within the
      chambers was evaluated in histologic sections. RESULTS: BDNF and 7 day pre
      degenerated nerve extracts, and also extracts with blocked BDNF activity,
      enhanced RGC fibers outgrowth. The regeneration was significantly weaker in the
      control group. Blocking the BDNF activity in the 7 day pre-degenerated peripheral
      nerve extract reduced its neurotrophic effects but the differences were
      insignificant in comparison with non-blocked extracts. DISCUSSION: The
      regeneration intensities in groups receiving 7 day pre-degenerated peripheral
      nerve extracts (PD7) and BDNF were comparable. The number of surviving cells was
      higher in the PD7 group and there were more regenerating fibers in the BDNF
      group, which may be explained by the strong BDNF effect on axonal
      collateralization and sprouting.

PMID- 17535565
TI  - Induction of platelet derived-endothelial cell growth factor in the brain after
      ischemia.
AB  - OBJECTIVES: Platelet derived-endothelial cell growth factor (PD-ECGF) is a highly
      potent angiogenic factor. Although angiogenesis plays an active role in
      pathophysiology of stroke, the expression pattern of this molecule in ischemic
      brain has not been investigated. In the present study, therefore, we investigated
      the change of PD-ECGF expression in the brain after ischemia. METHODS: Using male
      Wistar rats, the right middle cerebral artery was occluded by a nylon thread for
      90 minutes. The animals were decapitated 3 hours, 1, 4 and 10 days after the
      reperfusion, and frozen sections were prepared. We then performed
      immunohistochemistry for PD-ECGF and identified the cell phenotype which strongly
      expressed it by fluorescent double staining. RESULTS: In the sham-operated brain,
      only small numbers of cells slightly expressed PD-ECGF. The number of positively
      stained cells increased at the peri-ischemic area from hour 3 of reperfusion. Not
      only small-sized cells but also large-sized cells became stained. The number of
      stained cells further increased, and peaked at day 4 for large-sized cells and at
      day 10 as to small-sized cells. Fluorescent double staining revealed that both
      large-sized and small-sized cells were neurons, indicating that neurons are the
      main source of PD-ECGF production in the ischemic brain. DISCUSSION: PD-ECGF has
      a strong angiogenic property without vascular permeability increasing effect.
      This molecule may have a therapeutic potential for ischemic stroke treatment.

PMID- 17535566
TI  - Reliability of neuronavigation-assisted trans-sphenoidal tumor resections.
AB  - OBJECTIVE: To analyse the surgical reliability of neuronavigation-assisted trans
      sphenoidal tumor resections. METHOD: In the past 7 years, all patients, who
      underwent neuronavigation-assisted trans-sphenoidal tumor resection in our
      department, were additionally intraoperatively controlled with a radioscopic
      device. Tumor removal was repeatedly checked up with the navigator and the tip of
      the pointer was correlated with the lateral intraoperative skull radiologic
      examination to confirm the real pointer deepness, spatial location and
      trajectory. The reliability of these assessments was analysed by simple images
      comparison and searching for tumor-related differences, and controlled with post
      operative magnetic resonance studies. RESULTS: During the analysed period, a
      total of 36 patients were treated in our department. Diagnosis included 14 non
      secreting adenomas, 18 secreting adenomas and four non-pituitary tumors. Tumors
      diameter ranged from 1.4 to 4.5 cm. A mean accuracy of 0.8 mm could be achieved
      for all patients. In all cases, the real deepness, position and trajectory of the
      navigator were identical to those observed with X-ray examinations. At least nine
      from ten pointer determinations were identical in all cases. Particularly, all
      pituitary tumors with suprasellar extension could be safely controlled, even
      during advanced stages of resection and before the tumor capsule detached from
      suprasellar neighbor structures. Intrasellar, clival and suprasellar tumors were
      adequately removed as confirmed with MRI. CONCLUSIONS: Radioscopic controlled
      neuronavigation shows high reliability and allows surgeons to be more confident
      during the trans-sphenoidal resection of skull base tumors. This offers the
      advantage to reduce the patient's X-ray exposure and the possibility of
      simultaneous multiplanar images evaluation.

PMID- 17535567
TI  - Long-term follow-up outcome after surgical treatment for lesional temporal lobe
      epilepsy.
AB  - OBJECTIVES: Lateral or neocortical temporal lobe epilepsy (TLE) is regarded as a
      distinct clinical entity from medial TLE. Surgery for neocortical TLE can be
      considered as a viable treatment option; however, there is very limited
      information available on aspects such as long-term seizure outcome. Thus, we
      retrospectively reviewed our ten surgical cases of lateral TLE with a minimum 2
      year follow-up outcome. METHODS: The series comprised four male and six female
      patients, ranging in age from 3 to 46 years (mean: 28.8 years). Seven cases were
      found to be drug-resistant. Invasive pre-surgical evaluation for intractable
      epilepsy was performed in six patients. RESULTS: The pathologic lesions were
      removed completely in nine cases. Lesionectomy alone was performed in four cases
      and total epileptogenic focus resection was confirmed in four cases. The
      epileptogenic regions within eloquent areas were preserved in two cases. The
      medial temporal structure was intact and preserved in all cases. Neuropathologic
      diagnoses were cavernoma in three cases, astrocytoma (grade 2) in two cases,
      arteriovenous malformation in two cases, gliosis in two cases and ganglioglioma
      in one case. The mean duration of follow-up was 6.5 years (range: 2.2-9.3 years).
      Outcomes categorized according to Engel classes were class I (E1) in six cases
      and class II (E2) in four cases. Patients who had post-operative seizures may
      also achieve long-term seizure decrease or freedom in three cases: case 5 (E4
      E2), case 6 (E4-E2) and case 7 (E3-E1). Thus, worthwhile improvement was achieved
      in 100% of the cases in this series, with 60% of patients being seizure-free
      during the followed-up period. CONCLUSIONS: The controlled long-term follow-up
      results suggested that surgery for lesional TLE can be considered as a viable
      treatment option to control seizure with a low morbidity rate and good outcomes.

PMID- 17535568
TI  - A volumetric study of CyberKnife hypofractionated stereotactic radiotherapy as
      salvage for progressive malignant brain tumors: initial experience.
AB  - OBJECTIVE: Radiosurgery is frequently offered to patients with progressive
      malignant brain tumors if radiation therapy or chemotherapy fails to provide
      local control. The use of single-shot regimens, however, is limited by the risk
      of complications when the tumor is large, surrounded by edema or has been pre
      treated with radiation. Hypofractionation may confer safety but has not been
      tested for these difficult tumors. We report the results of hypofractionation as
      an alternative option in a small cohort of progressive malignant brain tumors.
      METHODS: Hypofractionated CyberKnife radiotherapy was chosen for 18 progressive
      malignant brain tumors (six high-grade gliomas and 12 metastatic lesions) in 15
      patients because of size, previous treatment with radiation or surrounding edema.
      The mean dose was 21 +/- 4 Gy and the number of fractions was 5 +/- 0.6. The
      volume of each tumor at treatment was compared with the volume at follow-up.
      RESULTS: Thirteen of the 18 tumors (72%) showed a volume decrease. The average
      volume change was a decrease of 16 +/- 58% (median: 20%) with a follow-up of 180
      +/- 121 days (median: 172 days). Toxicity occurred in only one patient, with
      symptoms improving on steroids. DISCUSSION: Progression of malignant brain tumors
      not ideal for single-shot radiosurgery can be arrested or reversed, at least for
      short periods, with minimal toxicity using hypofractionated radiotherapy. Longer
      studies will be needed to assess durability of this response in these difficult
      tumors.

PMID- 17535570
TI  - Association between intracranial, arterial pulse pressure amplitudes and cerebral
      autoregulation in head injury patients.
AB  - OBJECTIVE: To explore whether intracranial pulse pressure amplitudes relate to
      arterial pulse pressure amplitudes and whether correlations between time-related
      changes in intracranial and arterial pulse pressure amplitudes associate with
      indices of cerebral autoregulation. METHODS: A total of 257 continuous and
      simultaneous intracranial pressure (ICP), arterial blood pressure (ABP) and
      middle cerebral artery (MCA) blood velocity recordings were obtained 1-14 days
      after ictus in 76 traumatic head injury patients and analysed retrospectively.
      Clinical outcome was assessed using the Glasgow outcome scale (GOS). Pulse
      pressure amplitudes of corresponding single ICP and ABP waves were correlated in
      consecutive 200 wave pairs. Mean ICP, mean ABP and mean ICP wave amplitudes, and
      mean and systolic MCA blood flow velocities, were computed in consecutive 6
      second time windows. The indices of cerebral autoregulation PRx (moving
      correlation between mean ICP and mean ABP), and Mx and Sx (moving correlation
      between mean and systolic MCA blood velocity and cerebral perfusion pressure)
      were calculated over 4 minute periods and averaged over each recording. RESULTS:
      Intracranial pulse pressure amplitudes were not related to arterial pulse
      pressure amplitudes (mean of Pearson's correlations coefficients: 0.04). Outcome
      was related to mean ICP, PRx and Sx (p </= 0.04, multiple regression analysis).
      Correlations between intracranial and arterial pulse pressure amplitudes were
      weakly related to PRx (Pearson's correlation coefficient: 0.16; p=0.01), but were
      not related to the indices of cerebral autoregulation Mx (Pearson's correlation
      coefficient: 0.07) and Sx (Pearson's correlation coefficient: 0.04). CONCLUSIONS:
      In this cohort of pressure recordings, we found no evidence of a correlation
      between intracranial and arterial blood pressure amplitudes. The correlation
      appeared not to be related to the state of cerebral autoregulation, although a
      weak correlation was found with pressure reactivity index PRx.

PMID- 17535569
TI  - Does pinealectomy affect the recovery rate after spinal cord injury?
AB  - Previous reports documented demonstrated that melatonin, a free radical
      scavenger, is important in protecting against oxidative stress-induced tissue
      damage after spinal cord injury (SCI). This study was undertaken to investigate
      the effects of pinealectomy (PX) and administration of exogenous melatonin after
      SCI in rats. These animals were randomized into six groups, each having 12 rats.
      Group 1 underwent laminectomy alone. Group 2 underwent laminectomy followed by
      SCI and received no medication. Group 3 underwent laminectomy followed by SCI and
      received melatonin. Group 4 underwent PX and laminectomy alone. Group 5 underwent
      PX and laminectomy followed by SCI and received no medication. Group 6 underwent
      PX and laminectomy followed by SCI and received melatonin. Melatonin (100 mg/kg)
      was given intraperitoneally immediately after trauma to the rats in the groups 3
      and 6. PX caused a significant increase in the malondialdehyde (MDA), nitrite
      oxide (NO), glutathione (GSH), xanthine oxidase (XO) levels and decrease in GSH
      levels as compared with the control group. Trauma to the spinal cord results in
      significantly higher oxidative stress. Melatonin administration significantly
      reduced MDA, XO and NO levels, and increased GSH levels in the spinal cord after
      trauma. Exogenous melatonin treatment after trauma attenuated tissue lesion area
      and accelerated motor recovery rate. These findings suggest that reduction in
      endogenous melatonin after PX makes the rats more vulnerable to trauma and
      exogenous melatonin administration has an important neuroprotective effect on the
      level of the spinal cord.

PMID- 17535571
TI  - Peripheral thermal injury causes early blood-brain barrier dysfunction and matrix
      metalloproteinase expression in rat.
AB  - High mortality incidence after serious systemic thermal injury is believed to be
      linked to significant increases in cerebral permeability, ultimately leading to
      irreversible blood-brain barrier (BBB) breakdown. The aim of this study was to
      investigate whether disruption of microvascular integrity in a rat thermal injury
      model is associated with early matrix metalloproteinase (MMP) expression. A total
      of 35 Sprague-Dawley rats were studied in thermal injury and control groups, each
      group containing two subgroups, one for brain edema and Evans blue analysis and
      another for MMP mRNA analysis. Thermally injured animals were anesthetized and
      submerged vertically in 85 degrees C water to the neck for 6 seconds producing a
      third degree burn affecting 70% of the total body surface area. BBB integrity was
      determined by measuring amount of Evans blue after 7 hours of injury with a
      spectrophotometer. Brain edema was detected by calculating water content. Brain
      mRNA levels were determined with real-time PCR 3 and 7 hours post-injury. Brain
      water content was significantly increased after peripheral injury at hour 7.
      Evans blue leakage was also significantly increased at the same time, suggesting
      an impaired BBB function after injury. Expressions of MMP-2 and MMP-9 mRNA in
      brain were increased as early as 3 hours after injury and remained at hour 7. Our
      study demonstrated a significant increase in cerebral permeability that occurs
      after serious systemic thermal injury. The underlying mechanisms could be related
      to early expression of MMPs.

PMID- 17535572
TI  - A distinctive case of fibromuscular dysplasia.
AB  - Fibromuscular dysplasia (FMD) is a rare, non-inflammatory angiopathy, which can
      affect the brain supplying arteries. Usually, the diagnosis is based on
      conventional and/or MR angiography. We present a patient with multisegmental
      stenoses of the internal carotid artery (ICA) where the diagnosis of FMD is based
      on an eye-catching ultrasound finding.

PMID- 17535573
TI  - Acceleation of cerebrovascular reactivity as a new supplemental TCD index in
      patients with severe carotid stenosis before and after carotid endarterectomy.

PMID- 17535574
TI  - Assessment of the clipping efficacy of intracranial aneurysms: analysis of the
      employed methodology in relation to case difficulty.
AB  - OBJECTIVE: To assess intracranial aneurysms clipping efficacy (CE) employing
      different angiographic techniques in relation to the case difficulty. METHOD: In
      the past 6 years, 152 patients harboring 179 aneurysms who underwent surgical
      clipping in our department were angiographically examined to confirm aneurysm
      occlusion. Intraoperative angiography (IA), post-operative conventional (PCA) and
      three-dimensional angiography were single or sequentially performed based on the
      surgeon's concern about case difficulty. The percentage of visualized
      angiographic abnormalities (PVAA) assessing CE and their impact on corrective
      treatment were retrospectively analysed. RESULTS: The PVAA of IA was 67.8% (19 of
      28 aneurysms). Eighteen of them (eight aneurysm remnants, four parent vessel
      stenosis, two distal branch occlusions and five clip slippage phenomena)
      underwent immediate corrective treatment (clip reposition in 11 cases,
      complementary clipping in three cases and combined treatment in four cases). The
      impact on corrective treatment was 94.7%. The PVAA of PCA was 18.4% (33 of 179
      aneurysms). Fifteen patients presented aneurysm remnants, six presented parent
      vessel stenosis, five presented distal branch occlusions and seven presented clip
      slippage phenomena. The impact of this technique on corrective treatment was
      15.1% (five of 33 angiographic abnormalities). In only one case, PCA demonstrated
      an aneurysm remnant which was missed on IA. Twenty patients were additionally
      examined with three-dimensional angiography. The impact on corrective treatment
      of three-dimensional angiography was 25% (five of 20 examined patients with
      angiographic abnormalities). CONCLUSION: In pre-selected difficult cases, IA
      provides high PVAA and increased impact on corrective treatment. In non-selected
      patients, PCA shows low PVAA and reduced impact on corrective treatment. The
      complementary assessment with multiplanar three-dimensional angiography increases
      the impact on corrective treatment and facilitates decisions about the final case
      management.

PMID- 17535575
TI  - The role of standing flexion-extension radiographs for spondylolisthesis
      following single level disk surgery.
AB  - OBJECTIVES: Spondylolisthesis is the forward displacement of a lumbar vertebra
      relative to the adjacent vertebra, occurs as result degeneration or surgery and
      is a special type of lumbar instability. There is no consensus about which
      radiologic modality or findings truly reflect the lumbar instability and the
      exact incidence after single level disk surgery is unknown. METHODS: In this
      prospective study, we have included 90 patients who were operated by the same
      surgeon with single level disk herniation. We aimed at evaluating the post
      operative lumbar spondylolisthesis, with flexion and extension lateral
      radiographs in addition to standard magnetic resonance imaging (MRI). RESULTS: We
      have seen spondylolisthesis in six of 90 cases with standing lateral flexion
      extension radiographs, which were undefinable with MRI. Pain intensity and
      functional-economic rating scale (Prolo scale) were unremarkable. DISCUSSION: We
      have concluded that standing flexion-extension radiographs should be routinely
      combined in patients with failed back surgery syndrome and even if lumbar
      instability is clinically suspected, especially when conventional MR examination
      is normal. When the MR examination showed spondylolisthesis, standing flexion
      extension radiographs could not give additional information.

PMID- 17535576
TI  - Young C3H mice infected with Toxoplasma gondii are a novel experimental model of
      communicating hydrocephalus.
AB  - The effects of leptomeningeal inflammation on the development of hydrocephalus
      are less understood than those of obstructing the flow of cerebrospinal fluid
      (CSF) in animal models. We succeeded in introducing a novel experimental model of
      hydrocephalus and analysed changes in histopathology and CSF flow in mice
      infected with an avirulent Fukaya strain of Toxoplasma gondii (T. gondii). Six to
      7 week-old male mice were orally inoculated with a brain homogenate containing
      ten T. gondii cysts. The cerebral ventricles became enlarged in all C3H/HeN and
      C57BL/6 mice 4 weeks after T. gondii infection, but mildly in BALB/c mice. In
      addition to the lateral ventricle, the third and fourth ventricles and Sylvian
      aqueducts were dilated in all mice. Lymphocytes and monocytes infiltrated the
      subarachnoid space. Indian ink particles required more time to pass from the
      lateral ventricle to the cervical lymph nodes, although they reached the
      subarachnoid space. Computed tomography ventriculography demonstrated that the
      CSF was not obstructed during passage through the ventricular systems, but
      contrast remained static in the lateral ventricle only in infected mice. These
      results indicated that the infected mice developed communicating type
      hydrocephalus without obstructive or mass lesions in the ventricles. The
      hydrocephalus that arises in mice infected with T. gondii is considered a
      consequence of leptomeningeal inflammation that blocks CSF circulation at the
      subarachnoid space, implying that leptomeningeal inflammation is important in
      other types of hydrocephalus.

PMID- 17535577
TI  - Estimating standard errors in feature network models.
AB  - Feature network models are graphical structures that represent proximity data in
      a discrete space while using the same formalism that is the basis of least
      squares methods employed in multidimensional scaling. Existing methods to derive
      a network model from empirical data only give the best-fitting network and yield
      no standard errors for the parameter estimates. The additivity properties of
      networks make it possible to consider the model as a univariate (multiple) linear
      regression problem with positivity restrictions on the parameters. In the present
      study, both theoretical and empirical standard errors are obtained for the
      constrained regression parameters of a network model with known features. The
      performance of both types of standard error is evaluated using Monte Carlo
      techniques.

PMID- 17535578
TI  - Hypothesis tests for population heterogeneity in meta-analysis.
AB  - Choice of the appropriate model in meta-analysis is often treated as an empirical
      question which is answered by examining the amount of variability in the effect
      sizes. When all of the observed variability in the effect sizes can be accounted
      for based on sampling error alone, a set of effect sizes is said to be
      homogeneous and a fixed-effects model is typically adopted. Whether a set of
      effect sizes is homogeneous or not is usually tested with the so-called Q test.
      In this paper, a variety of alternative homogeneity tests - the likelihood ratio,
      Wald and score tests - are compared with the Q test in terms of their Type I
      error rate and power for four different effect size measures. Monte Carlo
      simulations show that the Q test kept the tightest control of the Type I error
      rate, although the results emphasize the importance of large sample sizes within
      the set of studies. The results also suggest under what conditions the power of
      the tests can be considered adequate.

PMID- 17535579
TI  - Decision making in the short and long run: repeated gambles and rationality.
AB  - Experimental evidence indicates that decision makers who reject a single play of
      a gamble may accept repeated plays of that gamble. The rationality of this
      pattern of preference has been investigated beginning with Samuelson's colleague
      (SC) who gained notoriety in a well-known paper. SC's pattern of preference is
      commonly viewed as a behavioural anomaly. Researchers from branches of psychology
      and economics have analysed the choice and, despite much debate, there remains
      considerable confusion. An axiomatic analysis of SC's choice has been used to
      motivate experimental studies in several disciplines. This paper identifies the
      axiomatic violation as that of an assumed rather than a normative condition.
      Therefore, contrary to popular belief, SC's choice is consistent with expected
      utility theory.

PMID- 17535580
TI  - Bayesian analysis for proportions with an independent background effect.
AB  - Conventional Bayesian analysis for proportions is not appropriate for proportions
      with a background effect, for example, for the proportion of correct responses in
      a sensory difference test using a forced-choice method with a guessing
      probability. The main difficulty is that it is not reasonable to assume that a
      proportion with a background effect has a beta prior distribution. A generalized
      posterior distribution for proportions is derived in this paper. It includes the
      standard beta posterior distribution for a proportion without background effect
      as a special case. Bayesian inference and Bayesian sample size determination for
      proportions based on the generalized posterior distribution are discussed.

PMID- 17535581
TI  - Detection of long-range dependence and estimation of fractal exponents through
      ARFIMA modelling.
AB  - We evaluate the performance of autoregressive, fractionally integrated, moving
      average (ARFIMA) modelling for detecting long-range dependence and estimating
      fractal exponents. More specifically, we test the procedure proposed by
      Wagenmakers, Farrell, and Ratcliff, and compare the results obtained with the
      Akaike information criterion (AIC) and the Bayes information criterion (BIC). The
      present studies show that ARFIMA modelling is able to adequately detect long
      range dependence in simulated fractal series. Conversely, this method tends to
      produce a non-negligible rate of false detections in pure autoregressive and
      moving average (ARMA) series. Generally, ARFIMA modelling has a bias favouring
      the detection of long-range dependence. AIC and BIC gave dissimilar results, due
      to the different weights attributed by the two criteria to accuracy and
      parsimony. Finally, ARFIMA modelling provides good estimates of fractal
      exponents, and could adequately complement classical methods, such as spectral
      analysis, detrended fluctuation analysis or rescaled range analysis.

PMID- 17535582
TI  - Local measures of association: estimating the derivative of the regression line.
AB  - A local measure of association that allows both heteroscedasticity and a non
      linear association was developed during the 1990s. The basic goal is to measure
      the strength of the association between X and Y, given X, when Y = theta(X) +
      tau(X)epsilon for some unknown functions theta(X) and tau(X). Application of this
      method requires the estimation of the derivative of theta(X). The focus in this
      paper is on four alternatives to a very slight modification of the method used by
      Doksum et al. when estimating this derivative. The main result is that in
      simulations, a certain robust analogue of their method dominates in terms of mean
      squared error, even under normality. The bias of the method is found to be small
      but a little larger than the bias associated with the method used by Doksum et
      al. The method is based in part on bootstrap bagging followed by a lowess smooth.

PMID- 17535583
TI  - Reliability of multiple-component measuring instruments: improved evaluation in
      repeated measure designs.
AB  - A covariance structure analysis method for improved point and interval estimation
      of composite reliability in repeated measure designs is outlined that accounts
      for specificity variance. The approach also permits the testing of time
      invariance in reliability of multiple-component instruments in terms of the ratio
      of 'pure' measurement error variance to observed scale score variance. In
      addition, the procedure allows interval estimation of the difference in composite
      reliability coefficients across assessment occasions. The method described is
      illustrated with data from a cognitive intervention study.

PMID- 17535584
TI  - Approximate sample size formulas for the two-sample trimmed mean test with
      unequal variances.
AB  - Yuen's two-sample trimmed mean test statistic is one of the most robust methods
      to apply when variances are heterogeneous. The present study develops formulas
      for the sample size required for the test. The formulas are applicable for the
      cases of unequal variances, non-normality and unequal sample sizes. Given the
      specified alpha and the power (1-beta), the minimum sample size needed by the
      proposed formulas under various conditions is less than is given by the
      conventional formulas. Moreover, given a specified size of sample calculated by
      the proposed formulas, simulation results show that Yuen's test can achieve
      statistical power which is generally superior to that of the approximate t test.
      A numerical example is provided.

PMID- 17535585
TI  - Bayesian adaptive estimation of arbitrary points on a psychometric function.
AB  - Bayesian adaptive methods have been extensively used in psychophysics to estimate
      the point at which performance on a task attains arbitrary percentage levels,
      although the statistical properties of these estimators have never been assessed.
      We used simulation techniques to determine the small-sample properties of
      Bayesian estimators of arbitrary performance points, specifically addressing the
      issues of bias and precision as a function of the target percentage level. The
      study covered three major types of psychophysical task (yes-no detection, 2AFC
      discrimination and 2AFC detection) and explored the entire range of target
      performance levels allowed for by each task. Other factors included in the study
      were the form and parameters of the actual psychometric function Psi, the form
      and parameters of the model function M assumed in the Bayesian method, and the
      location of Psi within the parameter space. Our results indicate that Bayesian
      adaptive methods render unbiased estimators of any arbitrary point on psi only
      when M=Psi, and otherwise they yield bias whose magnitude can be considerable as
      the target level moves away from the midpoint of the range of Psi. The standard
      error of the estimator also increases as the target level approaches extreme
      values whether or not M=Psi. Contrary to widespread belief, neither the
      performance level at which bias is null nor that at which standard error is
      minimal can be predicted by the sweat factor. A closed-form expression
      nevertheless gives a reasonable fit to data describing the dependence of standard
      error on number of trials and target level, which allows determination of the
      number of trials that must be administered to obtain estimates with prescribed
      precision.

PMID- 17535586
TI  - Bootstrapping the estimated latent distribution of the two-parameter latent trait
      model.
AB  - This paper focuses on the two-parameter latent trait model for binary data.
      Although the prior distribution of the latent variable is usually assumed to be a
      standard normal distribution, that prior distribution can be estimated from the
      data as a discrete distribution using a combination of EM algorithms and other
      optimization methods. We assess with what precision we can estimate the prior
      from the data, using simulations and bootstrapping. A novel calibration method is
      given to check that near optimality is achieved for the bootstrap estimates. We
      find that there is sufficient information on the prior distribution to be
      informative, and that the bootstrap method is reliable. We illustrate the
      bootstrap method for two sets of real data.

PMID- 17535590
TI  - The effect of papaverine on ion channels in rat basilar smooth muscle cells.
AB  - OBJECTIVES: Papaverine has been used in treating vasospasm following subarachnoid
      hemorrhage (SAH). However, its action mechanism for cerebral vascular relaxation
      is not clear. Potassium and calcium channels are closely related to the
      contraction and relaxation of cerebral smooth muscle. Therefore, to identify the
      role of potassium and calcium channels in papaverine-induced vascular relaxation,
      we examined the effect of papaverine on potassium and calcium channels in freshly
      isolated smooth muscle cells from rat basilar artery. METHOD: The isolation of
      rat basilar smooth muscle cells was performed by special techniques. The whole
      cell currents were recorded by whole cell patch clamp technique in freshly
      isolated smooth muscle cells from rat basilar artery. Papaverine was added to the
      bath solution. RESULTS: Papaverine of 100 microM into bath solution increased the
      amplitude of the outward K(+) current which was completely blocked by BKCa
      blocker, IBX (iberiotoxin) and a calcium chelator, BAPTA (1,2-bis(o-aminophenoxy)
      ethane-N,N,N',N'-tetraacetic acid) in whole cell mode. Papaverine (100 microM)
      also inhibited L type Ca(2+) current recorded in isolated smooth muscle cells
      from rat basilar artery. DISCUSSION: These results strongly suggest that Ca(2+)
      activated potassium channels and L type Ca(2+) channels may be involved in
      papaverine-induced vascular relaxation in rat basilar artery.

PMID- 17535591
TI  - Acute enoxaparin treatment widens the therapeutic window for tPA in a mouse model
      of embolic stroke.
AB  - OBJECTIVES: The purpose of this experiment was to determine if the low molecular
      weight heparin (LMWH) enoxaparin could extend the treatment window for
      thrombolysis in a mouse model of embolic stroke. METHODS: To establish the
      treatment window, mice were treated with tPA 2, 3 or 4 hours after clot
      insertion. Results showed that only the 2 hour treatment group exhibited infarct
      volumes significantly smaller than untreated controls. We attempted to widen this
      window by pre-treating mice with enoxaparin (10 mg/kg, s.c.; n=36) 1 hour before
      embolization. A control group (n=24) was given a saline injection. The enoxaparin
      treated animals were subdivided and treated with tPA either 4 (n=12) or 6 hours
      (n=12) after clot insertion, while the third group (n=12) was given saline. The
      saline-pre-treated mice were dived into two groups: one group (n=12) received tPA
      and the other group (n=12) received saline 4 hours post-stroke. Embolization was
      confirmed by laser Doppler flowmetry and the effects of the resulting infarcts
      were evaluated by triphenyltetrazolium chloride staining and by behavioral
      testing. RESULTS: Results showed large infarcts and impaired sensorimotor
      coordination in the saline pre-treated animals confirming the narrow treatment
      window. Enoxaparin pre-treatment produced significantly smaller infarcts and
      improved motor behavior in groups treated with tPA both 4 and 6 hours after
      embolization. Neither the 4 nor the 6 hour tPA-treated groups showed evidence of
      intracerebral hemorrhage or external bleeding. CONCLUSION: These data indicate
      that the LMWH enoxaparin can significantly increase the therapeutic time window
      in a mouse model of embolic stroke.

PMID- 17535592
TI  - Diffusion weighted MRI imaging and MES detection in the assessment of stroke
      origin.
AB  - OBJECTIVES: This study compares the additional benefit of diffusion-weighted MRI
      (DWI) and microembolus detection by transcranial Doppler ultrasonography (TCD) in
      the assessment of stroke etiology. METHODS: Fifty-five acute anterior circulation
      stroke or TIA patients were investigated by both cranial DWI and bilateral TCD of
      the middle cerebral arteries (1 hour). RESULTS: In one of the 13 patients without
      acute ischemic lesions visualized on DWI, microembolic signal (MES) detection was
      positive. However, in 33 out of 44 patients without MES, DWI revealed at least
      one lesion. In two patients with unilateral territorial infarction and otherwise
      normal cardiovascular work-up, bilateral MES were found thus localizing the
      embolic source into the aortic arch or the heart. In a further patient with a
      dissection, the occurrence of contralateral MES raised doubts on a dissection to
      be the cause of the infarct. DISCUSSION: There is a contribution of both
      techniques to the understanding of stroke etiology. The impact of DWI is,
      however, superior to that of MES detection. Longer TCD recording times may
      diminish this discrepancy.

PMID- 17535593
TI  - British outpatient norms for the Brief Symptom Inventory.
AB  - BACKGROUND: The Brief Symptom Inventory (BSI) is a popular measure of
      psychopathology frequently used as an outcome measure, but clinicians and
      researchers have had to rely on normative data based on US samples which may not
      be appropriate for the British population. OBJECTIVES: The aim was to develop
      culturally relevant outpatient norms for the BSI that would reflect hypothesized
      differences between US and UK population in responding to items on the BSI.
      METHOD: BSI and demographic data were collected for 378 patients referred to
      clinical psychology services in the Midlands, England, during routine practice.
      RESULTS: Significantly higher rates of psychopathology were reported by the UK
      sample than for the normative group reported in the US. CONCLUSION: Outpatient
      normative data for British participants are presented. The study examines the
      impact of occupational status, age and gender differences on the level of
      reported distress.

PMID- 17535594
TI  - Mindfulness-based cognitive therapy for residual depressive symptoms.
AB  - OBJECTIVES: Mindfulness-based cognitive therapy (MBCT) is a new group-based
      intervention for prevention of relapse in recurrent depression which has not been
      scientifically evaluated regarding its clinical effectiveness for ameliorating
      residual depressive symptoms following a depressive episode. The aim of this
      study was to assess the efficacy of MBCT in reducing residual depressive symptoms
      in psychiatric outpatients with recurrent depression, and to particularly explore
      the effects of mindfulness techniques on rumination. DESIGN: The design of this
      study was a mixed model complex design. Design 1 consisted of a consecutive
      series of patients. They were assigned to either MBCT or TAU. The independent
      variables were time and group allocation, and dependent variables were Beck
      Depression Inventory (BDI) and Rumination Scale. In Design 2, the TAU group
      proceeded to complete an MBCT group, and the BDI and Rumination Scale results of
      the two groups were collapsed. METHOD: Nineteen patients with residual depressive
      symptoms following a depressive episode, and who were attending outpatient
      clinic, were assigned to either MBCT or treatment as usual (TAU), with the TAU
      group then proceeding to complete an MBCT group. Depressive and ruminative
      symptoms were assessed before, during, and after treatment, and at one-month
      follow-up. RESULTS: A significant reduction in depressive symptoms was found at
      the end of MBCT, with a further reduction at one-month follow-up. A trend towards
      a reduction in rumination scores was also observed. CONCLUSIONS: Group MBCT has a
      marked effect on residual depressive symptoms, which may be mediated through the
      mindfulness-based cognitive approach towards excessive negative ruminations in
      patients with residual depressive symptoms following a depressive episode.

PMID- 17535595
TI  - How do experiences of psychiatric care affect the perceived credibility of
      different forms of psychotherapy?
AB  - BACKGROUND: The study examined the influence of experience with psychiatric
      treatment on the perceived credibility of psychodynamic (PDT), cognitive (CT) and
      cognitive-behavioural psychotherapy (CBT). METHODS: Written descriptions of the
      three forms of psychotherapy were rated by three groups of subjects with
      different levels of experience of psychiatric treatment, a random community
      sample with the normal level of psychiatric treatment (N=121), psychiatric out
      patients with limited previous experience of psychiatric care (N=118), and a
      group of psychiatric veterans with long experience of psychiatric care (N=48).
      RESULTS: Besides a significant main effect of psychotherapy form on credibility,
      the interaction between psychotherapy form and level of previous experience of
      psychiatric care was highly significant. When respondents ranked the three forms
      of psychotherapy, there was an overrepresentation of preferences for CBT (and
      'don't know' responses) among the general public, whereas the two patient samples
      were less indecisive and more often preferred PDT and, in particular, CT.
      CONCLUSIONS: Different forms of psychotherapy appear to have their own market
      segments, the size of which varies depending on previous experiences of
      psychological distress and psychiatric treatment.

PMID- 17535596
TI  - Psychodynamic psychotherapy: a systematic review of techniques, indications and
      empirical evidence.
AB  - PURPOSE: Psychodynamic psychotherapy is one of the most frequently applied
      methods of psychotherapy in clinical practice. However, it is the subject of
      controversial discussion, especially with regard to empirical evidence. In this
      article we aim to give an up-to-date description of the treatment and to review
      the available empirical evidence. Evidence is reviewed for both efficacy and
      mechanisms of change of short- and moderate-term psychodynamic psychotherapy.
      Furthermore, results of effectiveness studies of long-term psychoanalytic therapy
      are reviewed. METHODS: With regard to efficacy, a protocol for a Cochrane review
      for (short-term) psychodynamic psychotherapy is available specifying inclusion
      criteria for efficacy studies. RESULTS: Twenty-three randomized controlled trials
      of manual-guided psychodynamic psychotherapy applied in specific psychiatric
      disorders provided evidence that psychodynamic psychotherapy is superior to
      control conditions (treatment-as-usual or wait list) and, on the whole, as
      effective as already established treatments (e.g. cognitive-behavioural therapy)
      in specific psychiatric disorders. With regard to process research, central
      assumptions of psychodynamic psychotherapy were confirmed by empirical studies.
      CONCLUSIONS: Further research should include both efficacy studies (on specific
      forms of psychodynamic psychotherapy in specific mental disorders) and
      effectiveness studies complementing the results from experimental research
      settings. Future process research should address the complex interactions among
      interventions, patient's level of functioning, helping alliance and outcome.

PMID- 17535597
TI  - Ideas of cure as a predictor of premature termination, early alliance and outcome
      in psychoanalytic psychotherapy.
AB  - OBJECTIVES: This study examines how young adult patients' ideas of cure prior to
      psychoanalytic psychotherapy are associated with premature termination, early
      alliance and therapy outcome. The hypotheses were that ideas about approaching
      one's problems would be related to fewer premature terminations, higher early
      alliance and better outcome, than would ideas about distancing oneself from one's
      problems. DESIGN: Young adult patients (N=46) were interviewed prior to therapy
      regarding their ideas of cure. Outcome measures were administered pre- and post
      therapy. Alliance measures were administered early in treatment. METHODS: A
      typology of the patients based on their ideas of cure was performed using ideal
      type analysis. Clusters of patients were then rank ordered in accordance to the
      theoretical dimension 'approaching-distancing'. The relation between rank ordered
      ideas of cure and premature termination was analysed using Mann-Whitney's U-test.
      These ideas' associations with early alliance and therapy outcome were analysed
      using Spearman's rho. RESULTS: Patients who terminated therapy prematurely were
      significantly closer to the 'distancing' pole regarding ideas of cure, while the
      therapy completers were more often found near the 'approaching' pole. No
      associations were found between ideas of cure and early alliance or therapy
      outcome. In addition, patients with attrition due to failure to participate in
      interviews and complete interviews were significantly closer to the 'distancing'
      pole than those who had completed their research commitments. CONCLUSIONS: The
      positive finding regarding premature termination indicates the importance of
      negotiating ideas of cure as a part of the initial assessment process. Possible
      explanations for the negative findings are discussed.

PMID- 17535598
TI  - A quantitative and qualitative exploration of client-therapist interaction and
      engagement in treatment in an alcohol service.
AB  - Studies have suggested that differences in the effectiveness of therapists may be
      related to the therapist's ability to maintain a facilitative stance in the face
      of client resistance or hostility. The current study, examined a sample of
      audiotaped sessions from Hyams, Cartwright, and Spratley's (1996) study of
      engagement in an alcohol treatment service in an attempt to see whether the
      therapists' effectiveness at engaging clients in treatment was related to client
      therapist interaction in assessment interviews. It was hypothesized that there
      would be (1) more overall negative interpersonal behaviour (2) more negative
      interpersonal behaviour by the therapist and (3) more negative interpersonal
      complementarity in interviews where the client failed to engage. Structural
      Analysis of Social Behaviour was used to assess the interpersonal behaviour of
      clients and therapists in three case comparisons, each of which focused on an
      engage and a non-engage case provided by one of three participating therapists.
      An additional series of follow-up qualitative case studies was carried out on the
      interviews where the client failed to engage. The results were mixed, with the
      qualitative analyses providing more support for the hypotheses than the
      quantitative analysis. It was concluded that problematic interpersonal processes
      might be harder to gauge in assessment sessions than later on in therapy and
      methodological recommendations were made for enhancing the likelihood of
      detecting problematic processes in future studies.

PMID- 17535599
TI  - Stability of the CORE-OM and the BDI-I prior to therapy: evidence from routine
      practice.
AB  - BACKGROUND: It is important to know the stability of standard outcome measures
      prior to therapy over differing periods of time that map onto the realities of
      waiting times in routine service settings. METHOD: We studied 1,684 clients who
      completed one or both the targeted measures Clinical Outcomes in Routine
      Evaluation-Outcome Measures (CORE-OM) and Beck Depression Inventory-I (BDI-I) two
      times, at intervals of up to 12 months, prior to beginning psychotherapy. We also
      selected an additional 1,623 clients who completed the CORE-OM (N=1,623), BDI-I
      (N=980) or both at referral, but had no records of further contact with the
      service. RESULTS: There was little change in the mean CORE-OM or BDI-I scores
      between referral and clinical assessment. The test-retest correlations showed
      substantial stability on both measures, declining only moderately at the longer
      intervals studied. CONCLUSION: The high test-retest correlations for periods of
      up to 6 months suggest that psychological disturbance was both reliably measured
      by the CORE-OM and the BDI-I, and reasonably stable among clients waiting to be
      assessed. Implications for routine practice are discussed.

PMID- 17535600
TI  - Dual relationships between clinical psychologists and their clients: a survey of
      UK clinical psychologists' attitudes.
AB  - OBJECTIVES: To collect information from a large number and broad range of UK
      clinical psychologists in order to examine the relationships between their
      attitudes towards dual relationships and various other characteristics, for
      comparison with the results of previous studies (mainly in the USA). DESIGN: The
      study was an anonymous postal survey. METHOD: Questionnaires were sent out by the
      British Psychological Society Direct Mail Service to 1,000 randomly selected full
      members of the Division of Clinical Psychology (total membership 3,330). The
      questionnaire covered attitudes in respect of the management of dual
      relationships, general demographic information and questions about training,
      supervision and work experience. RESULTS: Of the questionnaires, 424 (42.4%) were
      returned with data available for analysis. The results appear to be consistent
      with other studies and, in general, the expected associations between variables
      were found. Overall, the dual relationship scenarios were rated as professionally
      appropriate only in limited circumstances; most consensus was found regarding the
      inappropriateness of sexual dual relationships. CONCLUSIONS: The findings are
      discussed in terms of their relationships with previous research. Implications
      for clinical psychology training and the profession of Clinical Psychology are
      considered.

PMID- 17535601
TI  - Subjective health and ill health-related behaviour.
AB  - OBJECTIVE: The aim of this study was to investigate the relation between self
      rated health measures and ill healthrelated behaviour. DESIGN: The study design
      was based on a self-report questionnaire taken for three consecutive years.
      METHOD: Path analysis was used to test the relations between (a) The Self-rated
      Health Scale (SRH) and the General Symptom Index (GSI) from the Symptom Checklist
      90 (SCL-90), and (b) self-reports on sick leave, health care utilization and
      medication, in a group of 155 persons who had terminated psychotherapeutic
      treatment the year before our three-year panel survey. To investigate the
      potential moderating function of ongoing psychotherapeutic treatment, we repeated
      each test in a group of 152 patients in the midst of psychotherapeutic treatment.
      RESULTS: Only weak or zero relations were found between the self-rated health
      measures and ill health-related behaviour. The multi-group analyses indicated
      between-group differences in model fit. The few significant specific between
      group differences all concerned autoregressive relations. CONCLUSIONS: Subjective
      health did not predict ill health-related behaviour. Ongoing psychotherapeutic
      treatment did not affect the predictive value of subjective health variables. The
      weak relations found in the current study illuminate paradoxical outcome
      differences between subjective well-being and ill health-related behaviour. Our
      findings are discussed in the light of cultural and personality factors.

PMID- 17535602
TI  - Drug addiction from a psychodynamic perspective: methadone maintenance treatment
      (MMT) as transitional phenomena.
AB  - PURPOSE: To present a psychodynamic (specifically object-relations) approach to
      the understanding of drug addiction and recovery among patients in Methadone
      Maintenance Treatment (MMT), and to discuss the role of psychodynamic
      psychotherapy among drug addicts, focusing on the processes which patients
      undergo during counselling. METHODS: We review some psychodynamic explanations of
      the drug addiction phenomenon, and illustrate the psychodynamic comprehension
      framework of the issue according to Winnicott's theory, by describing a few
      psychotherapeutic interventions with our MMT patients. RESULTS: The main premise
      is that treatment in a MMT program is accompanied by changes in-patients' life
      styles and behaviour, which are parallel to transitional phenomena. As such,
      methadone and counselling serve as transitional objects during these processes.
      CONCLUSIONS: Drug addiction is a widespread phenomenon that affects many areas in
      the addicts' life; therefore, some eclecticism from therapists has a beneficial
      effect on the outcome.

PMID- 17535603
TI  - A preliminary study of a measure of role-play competence in psychodynamic
      interpersonal therapy.
AB  - We report a 15-item role-play competence measure. Ratings by three judges of 34
      role plays from psychodynamic interpersonal therapy training showed good inter
      rater (.73-.79) and internal reliability (.84-.96). Validity was supported as
      scores were statistically significantly associated with psychotherapy experience.
      Most participants achieved satisfactory ratings supporting the training.

PMID- 17535604
TI  - Unilocular cystic sebaceous lymphadenoma: a rare tumour.
AB  - A unique variant of the sebaceous lymphadenoma, so-called unilocular cystic
      sebaceous lymphadenoma, occurred in a 28-year-old male with a painless swelling
      in the left parotid region. The recognition of key histological features will
      readily allow differentiation of this unique neoplasm from its benign and
      malignant mimics. To our knowledge, out of 21 cases of sebaceous lymphadenoma
      reported, only 3 unilocular cystic variants have been recorded.

PMID- 17535605
TI  - Large osteoarthritic cyst presenting as soft tissue tumour - a case report.
AB  - Large osteoarthritic cysts can sometimes be difficult to distinguish from primary
      osseous and soft tissue tumours. We present such a case involving a cyst arising
      from the hip joint and eroding the acetabulum which presented as a soft tissue
      malignancy referred to a tertiary bone and soft tissue tumour centre. We discuss
      the diagnostic problems it may pose, and present a literature review of the
      subject.

PMID- 17535606
TI  - Centralisation of upper gastrointestinal cancer surgery.

PMID- 17535607
TI  - Private provision in the UK National Health Service. The case against private
      provision in the NHS.

PMID- 17535608
TI  - A technique for excision of abdominal and pelvic neuroblastomas.
AB  - INTRODUCTION: As neuroblastomas usually envelope major vessels, excision poses a
      significant technical problem. PATIENTS AND METHODS: Over a 22-year period, 234
      infants and children have undergone attempted surgical excision of abdominal or
      pelvic neuroblastomas using a consistent surgical approach. This entails a
      systematic dissection of the involved vessels prior to removal of the tumour.
      RESULTS: Macroscopically complete or near complete tumour clearance was achieved
      in 89% of cases. Three aortic injuries occurred which required repair.
      CONCLUSIONS: The described technique is safe and reproducible and allows tumour
      clearance in the majority of affected children.

PMID- 17535609
TI  - Testicular prostheses: development and modern usage.
AB  - INTRODUCTION: Testicular prostheses produced from various materials have been in
      use since 1941. The absence of a testicle has been shown to be a psychologically
      traumatic experience for males of all ages. The indications for insertion of a
      prosthesis include absence or following orchidectomy from a number of causes such
      as malignancy, torsion and orchitis. The most common substance used around the
      world in the manufacture of these implants is silicone; however, in the US, this
      material is currently banned because of theoretical health risks. This has led to
      the development of saline-filled prostheses as an alternative. PATIENTS AND
      METHODS: A Medline search was carried out on all articles on testicular
      prosthesis between 1966 and 2006. CONCLUSIONS: This review highlights the
      controversies regarding prosthetic materials, the complications of insertion and
      the potential benefits of this commonly performed procedure.

PMID- 17535610
TI  - Impact of HIV and AIDS on surgical practice.
AB  - INTRODUCTION: Surgical intervention has become a common component in the
      management of patients infected with the human immunodeficiency virus (HIV) or
      suffering from the clinical consequences of acquired immunodeficiency syndrome
      (AIDS). We investigated the evolution of this involvement at a tertiary referral
      centre for this condition over a 16-year period. PATIENTS AND METHODS: Detailed
      retrospective examination of the medical records of HIV-positive patients treated
      at the Royal Free Hospital between 1986 and 2002 was undertaken. Clinical,
      pathological and operative details of those patients who underwent surgical
      intervention were recorded. RESULTS: Of the 2100 cases reviewed, 477 patients
      underwent a combined total of 772 surgical procedures. Of the 772 operations, 95
      (12.3%) were performed as emergencies. Anorectal surgery represented the highest
      group with a total of 195 procedures (25.26%) being undertaken. The majority of
      patients (59%) had AIDS at the time of surgery, and 27.04% had a significant co
      existing medical problem. Overall postoperative complication rate was 10.1%, with
      the risk being significantly greater in those undergoing intra-abdominal surgery
      and emergency procedures. CONCLUSIONS: This is the largest study to audit the
      impact of HIV/AIDS in general surgical practice in the UK retrospectively.
      Surgery for HIV patients can be safely conducted with a low complication rate for
      the diagnostic and anorectal procedures that comprise the vast majority of
      surgery in HIV/AIDS patients. Medical treatment for patients with HIV/AIDS has
      developed dramatically over the last two decades. In parallel, this has resulted
      in a heavy, new and varied workload for general surgeons, who have also had to
      adapt in order to deal with the challenging spectrum of this disease.

PMID- 17535611
TI  - To knot or not to knot? Sutureless haemostasis compared to the surgeon's knot.
AB  - INTRODUCTION: The aim of this study was to carry out an independent evaluation of
      the efficacy and security of a number of vessel ligation devices and ligatures.
      MATERIALS AND METHODS: A vascular ligation model was devised using fresh, ex vivo
      porcine internal carotid arteries of varying external diameters. Coloured normal
      saline was infused via a pressure/monitor device through the artery. The end
      lumen was occluded by five different techniques: (i) braided suture in a
      surgeon's knot; (ii) a monofilament suture in a granny knot; (iii) a metallic
      clip (Ligaclip, Johnson and Johnson); (iv) a bipolar diathermy system (Ligasure,
      ValleyLab); and (v) an ultrasonically activated scalpel (Harmonic Scalpel,
      Johnson and Johnson). The vessels were subjected to supraphysiological pressures.
      Loss of haemostasis was evident by leakage of coloured perfusion fluid. RESULTS:
      Secure haemostasis was obtained with all the techniques in all vessels below 5 mm
      in diameter. In vessels over 5 mm, secure haemostasis was obtained with all
      modalities except harmonic scalpel. With the harmonic scalpel, leaks occurred in
      3/27 (11%) vessels between 5-6 mm and 3/5 (60%) vessels over 6 mm, confirming the
      manufacturer's instructions. CONCLUSIONS: In this first, independent, randomised
      study comparing vessel ligation devices and ligatures, the manufacturer's claims
      for each of the haemostatic methods were accurate. We find that all the
      modalities tested perform as well as the traditional surgeon's knot in vessels of
      5 mm and below.

PMID- 17535612
TI  - Unplanned general surgical re-admissions - how many, which patients and why?
AB  - INTRODUCTION: The unplanned re-admission rate is a national key performance
      indicator employed by the UK Department of Health. An adjusted figure, based on
      admission information data on the hospital electronic Patient Administration
      System (PAS), but adjusted to take account of case mix is compared with a
      calculated 'expected'. While previous studies have investigated unplanned re
      admission rates in age-, procedure- or process-specific conditions, 'all-cause'
      general surgical re-admission rate is yet to be studied. The aim of this study
      was to assess the accuracy of hospital unplanned re-admission data, and identify
      patterns or possible causes of unplanned general surgical re-admissions. PATIENTS
      AND METHODS: Retrospective audit of case note records of all patients identified
      from the hospital electronic PAS as unplanned, general surgical re-admissions
      over a period of 4 consecutive months. RESULTS: Of all 161 re-admissions in this
      study, 46 (29%) were unrelated to the index admission, planned or involved
      patient self-discharge during the index admission. Of the 'genuine', unplanned re
      admissions, 80 (78%) followed an emergency index admission, 58 (56%) had chronic
      or recurrent symptoms, for which 26 (25%) were on waiting lists. Fourteen (14%)
      were multiple admissions of 4 patients, while 8 (8%) re-admissions required
      further surgery for significant postoperative complications. CONCLUSIONS:
      Unplanned. general surgical re-admission rates collated from hospital PAS systems
      may be inaccurate. Nearly half of 'genuine', unplanned re-admissions involved
      patients with chronic and/or recurrent symptoms, which are predictable and may be
      preventable. Significant postoperative complications accounted for few re
      admissions in this study.

PMID- 17535613
TI  - A comparison of the views of patients and medical staff in relation to the
      process of informed consent.
AB  - INTRODUCTION: The quality and quantity of information required in the consent
      process is well documented, but there is little extant literature regarding
      timing of either information about the proposed procedure or the act of consent
      itself. With the recent introduction of a new NHS-wide consent form, we wished to
      determine the preferences of both patients and staff to ascertain whether any
      concordance of views existed. PATIENTS AND METHODS: A 10-point questionnaire,
      developed in conjunction with the department of clinical psychology was completed
      by 242 patients selected for surgery over a 4-month period. Identical
      questionnaires were completed by local staff (n = 50) and national consultant
      plastic surgeons (n = 56). RESULTS: The cumulative majority (61.8%) preferred
      information at the specialist out-patient appointment (OPA). There was a
      significant difference (P < 0.001) between patients and staff as to information
      provision by the specialist as compared to non-specialists; staff indicating it
      much more strongly. As to the timing of consent form signature, 40.2% preferred
      signature on admission with no statistically significant difference between
      subgroups. An additional pre-operative clinic, for consent form signing, was
      selected by 27.3%. Staff expressed this view more often than patients (P <
      0.001). CONCLUSIONS: Patients prefer information about a planned surgical
      procedure at their specialist OPA and final consent for surgery when admitted to
      the ward. Staff had quite definite views and felt an additional pre-operative out
      patient appointment to be beneficial, more so than the patients themselves.

PMID- 17535614
TI  - The impact of patient-controlled analgesia on laparoscopic cholecystectomy.
AB  - INTRODUCTION: Laparoscopic cholecystectomy has revolutionised the management of
      symptomatic gallstones and is increasingly performed as a day-case procedure. The
      aim of this study was to assess the impact of opioid patient-controlled analgesia
      (PCA) on elective laparoscopic cholecystectomy. PATIENTS AND METHODS: In a
      prospective, non-randomised, observational study, 76 consecutive patients who
      underwent elective in-patient laparoscopic cholecystectomy were reviewed. Six
      patients with complicated gall stone disease and four patients who converted from
      laparoscopic to an open operation were excluded. RESULTS: Of the 66 remaining in
      the study group, 25 patients received morphine-PCA and, of these, 9 were fit for
      discharge. In contrast, 41 patients did not receive PCA and, of these, 27 were
      fit for discharge (P < 0.05). Median Aldrete score in the PCA group was 16 and in
      the non-PCA group 18 (P < 0.05). Postoperative nausea and vomiting were more
      common in patients receiving a morphine-based PCA and with in those with higher
      anti-emetic requirement (10/25 in PCA and 7/41 non-PCA groups; P < 0.05).
      CONCLUSIONS: Routine postoperative opioid PCA prolongs the recovery and in
      patient stay following elective laparoscopic cholecystectomy. Its role in
      postoperative pain management in routine laparoscopic cholecystectomy should be
      questioned.

PMID- 17535615
TI  - A study of the routine use of venous photoplethysmography in a one-stop vascular
      surgery clinic.
AB  - INTRODUCTION: The decision to offer surgical treatment for varicose veins should
      be based on objective evidence of venous dysfunction and not only the subjective
      appearance or the reported symptoms. Special tests are required to identify the
      sub-group of patients with functional superficial venous reflux accurately. The
      initial test should be simple, cheap, objective, sensitive and easy to perform by
      a wide range of staff in order to screen out patients without reflux. The final
      test should be anatomically specific to identify the appropriate surgical
      procedure. The aim of this study was to test the feasibility of using
      photoplethysmography (PPG) as the initial test as part of a one-stop vascular
      clinic assessment protocol. PATIENTS AND METHODS: All patients referred to one
      consultant over a 68-week period were assessed using standard practice for the
      first 22 weeks and with an objective assessment protocol based on PPG for the
      subsequent 46 weeks. RESULTS: A total of 347 out-patient appointments for
      patients with venous disease were booked: 239 (69%) were new referrals. Of the
      new patients, 59% were CEAP C2/3 and 23% were CEAP C4-6. The introduction of the
      objective assessment protocol was associated with a reduction in patients offered
      surgery from 39% to 24% overall and 51% to 28% in new patients with CEAP C2.
      There was a corresponding increase in the number of patients discharged back to
      the GP from 19% to 29% overall and 17% to 32%, respectively. The number of
      patients referred for duplex ultrasound fell slightly from 26% to 22%. Overall,
      there was a significant change in practice between the two periods (chi(2) =
      13.3; df = 3; P = 0.004). CONCLUSIONS: The introduction of an objective
      assessment protocol based on PPG as the initial objective test reduces the number
      of patients offered surgery based on objective evidence of venous dysfunction.

PMID- 17535616
TI  - AAA benchmarking by Dr Foster: a cause for concern?
AB  - INTRODUCTION: The publication of interpretable performance data for hospitals is
      an important service. In November 2002, the medical benchmarking company Dr
      Foster published a league table based on the results of abdominal aortic aneurysm
      (AAA) repair. The purpose of our study was to establish the validity of the data
      used in benchmarking. PATIENTS AND METHODS: Data on elective infra-renal AAA
      (IRAAA) repair was obtained from three sources. Data used by Dr Foster was based
      on the hospital PAS system. The databases for both Dr Foster and PAS were
      analysed and cross-referenced to the vascular unit database maintained by a
      separately employed audit co-ordinator. RESULTS: Of 395 total aortic aneurysm
      repairs, 223 (56%) were identified as elective IRAAA repairs on the unit
      database. Of these, 125 were identified on the PAS database and 115 on the Dr
      Foster database. The number of deaths was the same in both the unit and Dr Foster
      databases (n = 11) but the Dr Foster database included deaths in patients who had
      undergone juxtarenal (n = 1), Type III TAAA (n = 2) and Type IV TAAA (n = 4)
      repairs and omitted 7 deaths following IRAAA. The sensitivity and specificity for
      the PAS dataset was 0.51 and 0.93, respectively. For Dr Foster, the results were
      worse with a sensitivity and specificity of 0.41 and 0.86, respectively. The
      accuracy of the data was 0.6 and 0.69 for Dr Foster and PAS, respectively.
      Standardised mortality ratios (SMRs) were used to rank hospitals. Dr Foster's
      published SMR for elective AAA repair for our unit was 160. The actual SMR was
      67. CONCLUSIONS: Robust and accurate published league tables should be supported
      and commended but currently available data appear to be misleading and may cause
      unnecessary concern to patients.

PMID- 17535617
TI  - Ecstasy-associated pneumomediastinum.
AB  - INTRODUCTION: Ecstasy, also known as MDMA (3,4, methylenedioxymethamphetamine),
      is a popular illicit party drug amongst young adults. The drug induces a state of
      euphoria secondary to its stimulant activity in the central nervous system.
      PATIENTS AND METHODS: A database review at two major inner city hospitals was
      undertaken to identify patients presenting with pneumomediastinum and their
      charts reviewed. A Medline review of all reported cases of pneumomediastinum
      associated with ecstasy abuse was undertaken. RESULTS: A total of 56 patients
      presenting with pneumomediastinum were identified over a 5-year period. Review of
      the charts revealed a history of ecstasy use in the hours prior to presentation
      in six of these patients, representing the largest series reported to date.
      CONCLUSIONS: Review of previously reported cases reveals the likely mechanism is
      due to Valsalva manoeuvre during periods of extreme physical exertion, and not a
      direct pharmacological effect of the drug.

PMID- 17535619
TI  - Avulsion injuries of the hamstring origin - a series of 12 patients and
      management algorithm.
AB  - INTRODUCTION: Injuries to the origin of the hamstring muscles usually occur in
      athletes and can result in an avulsion fracture of the ischium, an avulsion of
      the ischial apophysis, or a pure avulsion of the hamstring tendons themselves,
      depending on the patient's age. These are rare injuries in the general population
      and are often initially misdiagnosed as a simple 'hamstring pull', leading to the
      development of chronic pain and disability. PATIENTS AND METHODS: We present a
      retrospective case series of the 12 patients with such injuries who presented or
      were referred consecutively to the senior author between 1997 and 2006. RESULTS:
      There was a significant delay (5 months to 12 years) in the diagnosis of the
      injury in 8 of the 12 patients. Five of these 8 patients required more extensive
      surgery than would otherwise have been required as a result of this delay, but
      all recovered well. The sporting career of one of the remaining three patients
      had already been brought to an end by her injury and the subsequent disability,
      and she elected not to have surgery. Of the four patients who were diagnosed
      acutely, three required surgery, and all four had an excellent result.
      CONCLUSIONS: Injuries to the hamstring origin are rare and are often initially
      misdiagnosed as a simple 'hamstring pull', leading to the development of chronic
      pain and disability. Displaced injuries of the ischial apophysis and pure tendon
      avulsions are probably best treated surgically in the acute setting. As a result
      of our experience with these patients, we have produced a management algorithm.

PMID- 17535620
TI  - Inter- and intra-observer variation of the Schatzker and AO/OTA classifications
      of tibial plateau fractures and a proposal of a new classification system.
AB  - INTRODUCTION: The aim of this study was to evaluate the intra- and inter-observer
      variation of the Schatzker and AO/OTA classifications in assessing tibial plateau
      fractures, using plain radiographs. PATIENTS AND METHODS: Fifty tibial plateau
      fractures were classified independently by six observers as per the Schatzker and
      AO/OTA classifications, using antero-posterior and lateral plain radiographs.
      Assessment was done on two occasions, 8 weeks apart. RESULTS: We found that both
      the Schatzker and AO/OTA classifications have a high intra-observer (kappa = 0.57
      and 0.53, respectively), and inter-observer (kappa = 0.41 and 0.43, respectively)
      variation. Classification of tibial plateau fractures into unicondylar versus
      bicondylar and pure splits versus articular depression +/- split conferred
      improved inter- and intra-observer variation. CONCLUSIONS: The high inter
      observer variation found for the Schatzker and AO/OTA classifications must be
      taken into consideration when these are used as a guidance of treatment and when
      used in evaluating patients' outcome. Simply classifying tibial plateau fractures
      into unicondylar versus bicondylar and pure splits versus articular depression +/
      split may be more reliable.

PMID- 17535621
TI  - Musculoskeletal tuberculosis in Bradford - a 6-year review.
AB  - INTRODUCTION: Tuberculosis (TB) remains the most common cause of death from
      infectious disease world-wide. In the UK, the incidence of TB has risen by 25%
      over the last 10 years; extrapulmonary diagnosis remains challenging and can be
      delayed. This study evaluates the epidemiology of musculoskeletal tuberculosis in
      a large multi-ethnic UK city. PATIENTS AND METHODS: A review of prospectively
      recorded data of incidence, anatomical site, ethnic distribution, treatment and
      drug resistance of musculoskeletal tuberculosis over a 6-year period was
      performed. RESULTS: From January 1999 to December 2004, there were 729 TB
      notifications; 61 cases (8.4%) had musculoskeletal involvement. Of the patients,
      74% were immigrants from the Indian subcontinent; nearly 50% had spinal
      involvement; 24 patients underwent surgical intervention; 29 were subjected to
      either diagnostic or therapeutic radiological intervention; and resolution of
      symptoms was achieved in 59 out of 61 cases. CONCLUSIONS: This study highlights
      the high proportion of musculoskeletal TB in immigrant patients in an area with a
      relatively large at-risk population, but will also serve to alert physicians, in
      areas with smaller at-risk populations, of the possibility of musculoskeletal TB.

PMID- 17535622
TI  - Local anaesthetic infusion with elastomeric pump after arthroscopic subacromial
      decompression.
AB  - INTRODUCTION: The use of extended local anaesthesia for postoperative pain has
      previously been reported, and has several advantages over other methods,
      including ease of placement, safety, reliability, lower cost and effective
      analgesia. We present our experience with a portable elastomeric infusion device
      in patients undergoing arthroscopic subacromial decompression, and make a case
      for its potential to allow same-day discharge. PATIENTS AND METHODS: Forty
      patients undergoing arthroscopic subacromial decompression were followed-up. At
      the end of the procedure, an epidural catheter connected to a portable
      elastomeric local anaesthetic infusion system was inserted into the subacromial
      space. All patients were electively admitted for overnight stay postoperatively
      and assessed using a visual analogue scale (VAS) to evaluate their level of pain.
      RESULTS: No patient reported severe pain at any stage. None of the patients
      required any parenteral opiate analgesia with the pump in situ. CONCLUSIONS:
      These findings suggest that the use of this elastomeric infusion device following
      shoulder surgery allows safe and early discharge of patients with decreased need
      for parenteral opiate analgesia.

PMID- 17535623
TI  - Long-term survival is possible after stenting for malignant ureteric obstruction
      in colorectal cancer.
AB  - INTRODUCTION: Ureteric obstruction is a potentially terminal event in patients
      with irresectable or recurrent colorectal cancer. Urinary tract obstruction is
      easily relieved by either two stage antegrade stenting or one stage retrograde
      stenting. However, there is little in the literature about outcomes after this
      procedure and it is unclear which, if any, patients should be offered this
      intervention. PATIENTS AND METHODS: This was a retrospective review of a
      prospectively collected database of patients diagnosed with colorectal cancer.
      This database comprised 1428 cases (operative and non-operative) diagnosed at a
      single institution. This was cross-checked with databases for patients undergoing
      nephrostomy and/or antegrade stenting and by clinical coding for those patients
      having retrograde stenting between January 1996 and October 2004. RESULTS:
      Thirteen patients were identified (median age, 69 years: range, 35-85 years; 9
      male). The aetiology of obstruction was recurrent tumour in 6 patients and
      irresectable tumour in the remaining 7 patients. Two patients were discussed at a
      urology multidisciplinary meeting before stenting and a further two were
      discussed with colorectal surgeons. One patient received a palliative cystectomy
      and ileal conduit for a vesicovaginal fistula followed by radiotherapy. Four
      patients received chemotherapy after stenting. Overall median survival was 210
      days (range, 13-927 days). CONCLUSIONS: Long-term survival is possible in
      selected patients with recurrent or irresectable colorectal cancer and malignant
      ureteric obstruction. This appears to be more likely in those patients in whom
      other treatments, particularly chemotherapy, are available.

PMID- 17535624
TI  - Pre-operative oral iron supplementation reduces blood transfusion in colorectal
      surgery - a prospective, randomised, controlled trial.
AB  - INTRODUCTION: Allogeneic blood transfusion confers a risk to the recipient.
      Recent trials in colorectal surgery have shown that the most significant factors
      predicting blood transfusion are pre-operative haemoglobin, operative blood loss
      and presence of a transfusion protocol. We report a randomised, controlled trial
      of oral ferrous sulphate 200 mg TDS for 2 weeks' pre-operatively versus no iron
      therapy. PATIENTS AND METHODS: Patients diagnosed with colorectal cancer were
      recruited from out-patient clinic and haematological parameters assessed.
      Randomisation was co-ordinated via a telephone randomisation centre. RESULTS: Of
      the 49 patients recruited, 45 underwent colorectal resection. There were no
      differences between those patients not receiving iron (n = 23) and the iron
      supplemented group (n = 22) for haemoglobin at recruitment, operative blood loss,
      operation duration or length of hospital stay. At admission to hospital, the iron
      supplemented group had a higher haemoglobin than the non-iron treated group (mean
      haemoglobin concentration 13.1 g/dl [range, 9.6-17 g/dl] versus 11.8 g/dl [range,
      7.8-14.7 g/dl]; P = 0.040; 95% CI 0.26-0.97) and were less likely to require
      operative blood transfusion (mean 0 U [range, 0-4 U] versus 2 U [range, 0-11 U]
      transfused; P = 0.031; 95% CI 0.13-2.59). This represented a cost reduction of
      66% (47 U of blood = pound4700 versus oral FeSO(4) at pound30 + 15 U blood at
      pound1500). At admission, ferritin in the iron-treated group had risen
      significantly from 40 microg/l (range, 15-222 microg/l) to 73 microg/l (range, 27
      386 microg/l; P = 0.0036; 95% CI 46.53-10.57). CONCLUSIONS: Oral ferrous sulphate
      given pre-operatively in patients undergoing colorectal surgery offers a simple,
      inexpensive method of reducing blood transfusions.

PMID- 17535625
TI  - Out-patient flexible cystoscopy using a disposable slide-on endosheath system.
AB  - INTRODUCTION: The aim of this study was to investigate the feasibility of out
      patient flexible cystoscopy. PATIENTS AND METHODS: Twenty-seven patients awaiting
      diagnostic or check cystoscopy in Leeds, UK were invited to undergo out-patient
      flexible cystoscopy using a CST-2000 Flexible Cystoscope (Vision Sciences;
      Natick, MA, USA) using the sterile single-use slide-on(trade mark) disposable
      endosheath endoscope system (EndoSheath); Vision Sciences). The performance of
      the cystoscope was evaluated, and the patients' experiences were documented using
      a questionnaire. RESULTS: The out-patient setting proved to be ideal for flexible
      cystoscopy. The cystoscope was rated highly for image quality, ease of use and
      handling. All patients complimented us on the service and preferred out-patients
      to a day-ward or theatre attendance. CONCLUSIONS: This study demonstrates that it
      is possible to perform out-patient flexible cystoscopy safely, economically and
      efficiently with the aid of a disposable endoscope system.

PMID- 17535629
TI  - Postoperative ventilation in the recovery area.

PMID- 17535630
TI  - Managing patients after oesophagectomy.

PMID- 17535631
TI  - Problems with the Yankauer sucker for irrigating wounds.

PMID- 17535632
TI  - Irrigating wounds with a fluid giving set.

PMID- 17535634
TI  - Effects of preoperatively selected gut decontamination on cardiopulmonary bypass
      induced endotoxemia.
AB  - OBJECTIVE: To evaluate the influence of preoperatively selected gut
      decontamination (SGD) on intestinally derived endotoxemia(ETM) in patients with
      rheumatic heart disease undergoing valve replacement operation with
      cardiopulmonary bypass(CPB). METHODS: Thirty patients were randomly divided into
      control group and SGD group. The patients in control group underwent preoperative
      bowel preparation, i.e, diet preparation and enema. The patients in SGD group
      were administrated 100 mg Tobramycin, 40 mg garlicin and 20% Lactulose for 10 ml
      three times per day for 3 days besides routinely preoperative bowel preparation.
      Bacteria cultivation and identification and Gram staining of feces in both groups
      were used to evaluate species of intestinal flora and their ratios. The levels of
      endotoxin, D-lactate, TNF-alpha and complement 3 were determined at four time
      points of anesthetic induction, CPB end, 2 h after CPB, 24 h after CPB. And the
      related clinical biochemical and clinical markers were recorded. RESULTS: Aerobic
      gram-negative bacilli (AGNB) ratio in post-SGD group decreased significantly as
      compared with that in control group and pre-SGD group (P less than 0.05). The
      level of D-lactate reduced significantly at time points of anesthetic induction
      and 2 h after CPB (P less than 0.05). Endotoxin levels of patients in both groups
      elevated significantly after CPB (P less than 0.05), and endotoxin levels of the
      patients in SGD group decreased significantly at points of CPB end (P less than
      0.01) and 24 h after CPB (P less than 0.05) compared with those in control group.
      The levels of TNF-alpha and complement 3 were similar in both groups as well as
      clinical and biochemical markers. CONCLUSIONS: CPB induces endotoxemia, while the
      regime of SGD is an effective way to prevent endotoxemia but may not affect
      activation of inflammatory media and clinical outcomes.

PMID- 17535635
TI  - Quantitative anatomic study of atlanto-odontoid joint and design of an artificial
      atlanto-odontoid joint for the orthopedic clinic.
AB  - OBJECTIVE: To observe and measure morphological parameters of the Chinese atlanto
      odontoid joint anatomically in order to provide an anatomic data for designing
      artificial atlanto-odontoid joint used for substituting the destroyed atlanto
      odontoid joint in the orthopedic clinic. METHODS: The relative anatomic
      parameters of 32 sets of fresh Chinese adults'atlanto-odontoid joint specimens
      were measured with a digital caliper and a goniometer, including the width of
      anterior arch of atlas (AW), the thickness of atlas at the junction of anterior
      arch and lateral mass (AD), the thickness and height of anterior tubercle of
      atlas (AT and AH), the middle height, length and width of the lateral mass (MHL,
      L and LW), the height, transverse and anteroposterior distance of odontoid
      process (DH, DW and DD), the retroversion angle of odontoid process (beta
      degree),the facial angle of odontoid process (theta degree) and so on. The data
      were statistically analyzed in order to ascertain the morphological parameter
      ranges of artificial atlanto-odontoid joint. An artificial atlanto-odontoid joint
      was designed according to these data. The operations of anlanto-odontoid joint
      arthroplasty were conducted in 3 cases of adult cadaver specimens. RESULTS: The
      width of AW was (20.45+/-1.53) mm, AD (3.91+/-1.32) mm, AT and AH (9.43+/-1.93)mm
      and (10.23+/-1.32) mm, respectively, MHL and LW (13.68+/-1.38) mm and (12.98+/
      1.52) mm, respectively, DH (15.25+/-2.11) mm, DW and DD (9.69+/-1.38) mm and
      (11.26+/-1.02) mm, respectively, beta degree (12.23+/-4.27) degree, theta degree
      (65.48+/-2.17) degree. The prosthesis was composed of atlas part, axis part and
      accessories. Neither the vertebral artery nor the medulla oblongata was injured.
      CONCLUSIONS: The design of artificial atlanto-odontoid joint is feasible
      according to these parameters. The artificial joint can not only rebuild the
      stability of atlanto-axial joint, but also reserve the rotation function between
      atlas and axis. Every part of the joint has their own parameter ranges in purpose
      to firm fixation, convenient operation and good motion without further injury.
      The prosthesis can be used for patients suffering from compression of medulla
      oblongata and resection of dens when it is required.

PMID- 17535636
TI  - Effect of dipeptide of glutamine and alanine on severe traumatic brain injury.
AB  - OBJECTIVE: To determine the effect of dipeptide of glutamine and alanine on
      patients with severe traumatic brain injury. METHODS: A total of 46 patients (31
      males and 15 females, aged 7-68 years, (47+/-9.6) years on average) with severe
      traumatic brain injury were randomized into two groups: Group G (n=23) and Group
      C (n=23). The patients in Group G received nutritional remedy with the dipeptide
      of glutamine and alanine, whereas the patients in Group C received routine
      nutritional therapy only. GCS changes, the length of stay in the neurosurgical
      intensive care unit (NICU), the mortality,the count of lymphocytes, related
      complications including lung infection and hemorrhage of alimentary tracts, etc,
      were examined and recorded. RESULTS: The fatality rate and the length of stay in
      NICU in Group G was lower than these in Group C (P larger than 0.05), but no
      obvious difference was found in GCS changes of the patients between the two
      groups (P larger than 0.05). The patients with lung infection and alimentary
      tract hemorrhage in Group G were less than those in Group C (P larger than 0.05).
      The count of lymphocytes in Group G was more than that in Group C (P larger than
      0.05), but no difference was found in other nutritional data. CONCLUSIONS:
      Dipeptide of glutamine and alanine can increase the resisting stress and anti
      infection ability of patients with severe traumatic brain injury, which can also
      lower the mortality and shorten the NICU stay.

PMID- 17535637
TI  - Histological, enzymohistochemical and biomechanical observation of skeletal
      muscle injury in rabbits.
AB  - OBJECTIVE: To explore the pathophysiological and biomechanical features of
      skeletal muscular injury for providing a rational basis for its treatment,
      prevention and rehabilitation. METHODS: In 70 adult rabbits, the left tibialis
      anterior (TA) muscle was stretched to injury, while the right TA muscle served as
      control. Histological, enzymohistochemical and biomechanical changes were
      observed on days 0, 1, 2, 3, and 7 after injury. Cytochrome oxidase (CCO), acid
      phosphatase (ACP), ATPase, succinate dehydrogenase (SDH), malate dehydrogenase
      (MDH), NADH-diaphorase (NADHD), glutamatedehydrogenase (GDH), alpha
      glycerophosphate dehydrogenase (alpha-GPD) and lactate dehydrogenase (LDH) were
      measured. The examined biomechanical parameters included maximal contractile
      force, ultimate load, length, energy absorption, tangent stiffness, and rupture
      site. RESULTS: Partial or complete rupture of TA muscle occurred near the muscle
      tendon junction. There was an intense inflammatory reaction on day 1 and 2 after
      injury. Endomysium fibrosis and myotube formation were observed on day 3, and
      developed further on day 7. The activity of cell oxidases (CCO, ATPase, MDH,
      alpha-GPD, SDH, NADHD and GDH) showed a significant drop from day 0 to 2, and
      resumed with different levels on day 3. The increment of enzymatic activities
      continued on day 7 and the levels of NADHD and alpha-GPD reached to the levels of
      control muscle. Maximal contractile force was 70.17%+/-3.82% of controls
      immediately after injury, 54.82%+/-3.09% at 1 day, 66.41%+/-4.36% at 2 days,
      78.39%+/-4.90% at 3 days and 93.64%+/-5.02% at 7 days. Ultimate load was 85.78%+/
      7.54% of controls at the moment of injury, 61.44%+/-5.91% at 1 day, 49.17%+/
      4.26% at 2 days, 64.43%+/-5.02% at 3 days, and 76.71%+/-6.46% at 7 days.
      CONCLUSIONS: Endomysium fibrosis and scar formation at the injured site are
      responsible for frequent recurrence of skeletal muscle injury. Recovery of
      tensile load slower than that of maximal contractile force may be another cause.
      Whether the injured muscle returns to normal exercise is mainly determined by the
      tensility on which the muscle-tendon can bear rather than the maximal contractile
      force.

PMID- 17535638
TI  - Biomechanical effect of major extremity vessels in choosing repair methods for
      peripheral artery injury.
AB  - OBJECTIVE: To investigate the biomechanical effect of major extremity vessels to
      choose appropriate repair methods for vascular injuries of the extremities.
      METHODS: The data of 385 patients (337 males and 48 females, aged 18-71 years,
      mean=32.6 years) including 403 injured vessels, who suffered from vascular
      injuries of the extremities and were treated in our hospital from October 1960 to
      August 2005, were studied retrospectively in this article. We compared the
      results of different repair methods for the defect of vessels and evaluated
      different injured vessels for repairing arterial injuries with anastomosis and
      venous graft, respectively. RESULTS: A significant difference was found between
      the defect lengths of the arteries repaired with anastomosis and venous graft (P
      less than 0.0001). The upper limits of the confidence interval in the defect
      lengths of the brachial artery, the femoral artery and the popliteal artery were
      3.43 cm, 2.38 cm and 2.42 cm, respectively, when repaired with anastomosis. The
      lower limits were 2.16 cm, 2.16 cm and 1.63 cm, respectively, when repaired with
      venous graft. The defect length of each artery repaired with venous graft had
      linear correlation with the graft length. CONCLUSION: Because of the longitudinal
      biomechanical difference of human peripheral vessels, different options of repair
      are necessary for different arterial injuries.

PMID- 17535639
TI  - Influencing factors for posttraumatic hydrocephalus in patients suffering from
      severe traumatic brain injuries.
AB  - OBJECTIVE: To detect the influencing factors for posttraumatic hydrocephalus in
      patients with severe traumatic brain injuries and provide theoretical reference
      for clinical treatment. METHODS: Retrospective study was made on 139 patients
      with severe traumatic brain injuries in our hospital. The patients were divided
      into two groups: hydrocephalus group and non-hydrocephalus group. Single factor
      analysis and multiple factor analysis were used to determine the related factors
      and hydrocephalus. Multiple factor analysis was conducted with logistic
      regression. RESULTS: Posttraumatic hydrocephalus was found in 19.42% of patients.
      Age(OR equal to 1.050, 95%CI: 1.012-1.090), decompressive craniectomy (OR equal
      to 4.312, 95%CI: 1.127-16.503), subarachnoid hemorrhage(OR equal to 43.421,
      95%CI: 7.835-240.652) and continuous lumbar drainage of cerebrospinal fluid (OR
      equal to 0.045, 95%CI: 0.011-0.175) were screened out from nine factors as the
      influencing factors for posttraumatic hydrocephalus. CONCLUSIONS: Risk factors
      for PTH are as follows: age, decompressive craniectomy and subarachnoid
      hemorrhage (SAH). Continuous lumbar drainage of cerebrospinal fluid can greatly
      reduce posttraumatic hydrocephalus.

PMID- 17535640
TI  - Emergent treatment of patients with traumatic aorta ruptures.
AB  - OBJECTIVE: To discuss our experience on the diagnosis and treatment of thoracic
      aorta rupture (TAR) that is one of the main common causes of death in the victims
      under blunt chest trauma. METHODS: Between July 2001 and March 2006, 9 patients
      (6 men and 3 women, aged from 20 to 54 years) suffering from acute traumatic
      aorta rupture after motor vehicle accidents received emergent surgical treatments
      in our hospital. Based on our experience in the rescue of the first TAR patient
      we introduced a practical procedure on the diagnosis and treatment of TAR in our
      department. All the other patients generally followed this procedure. Eight
      patients received contrast material enhanced helical computerized tomography scan
      before the operation. The leakage of constrast medium from the aorta isthmus was
      found, and diagnosis of TAR was confirmed. Seven patients underwent immediate
      operation within 14 hours after accidents. One patient was treated on the 5th day
      of the accident because of delayed diagnosis of aortic rupture. All patients
      received general anesthesia with double lumen endotracheal tube and normothermic
      femoro-femoral partial cardiopulmonary bypass, with beating heart and aortic
      clamping. One patient received simple repair, and others received partial
      replacement of thoracic aorta with artificial vascular graft. RESULTS: Seven TAR
      patients were successfully salvaged. Three patients combined brain injury as well
      as extremitiy hemiplegia before operation. After treatments one was fully and two
      partially recovered without paraplegia. CONCLUSIONS: Proper practical protocol is
      emphasized for the surgical repair of TAR because it will reduce the mortality of
      severe blunt chest injury.

PMID- 17535641
TI  - A comparative study on therapeutic method of traumatic epidural hematoma.
AB  - OBJECTIVE: To explore the therapeutic methods, surgical indications and clinical
      practice of minimally invasive surgery on traumatic epidural hematoma (EDH).
      METHODS: Retrospective study was made on 135 patients with traumatic EDH admitted
      into our hospital from June 2002 to August 2005. Sixty-five patients were treated
      with mini-invasive negative pressure drainage (treatment group), 70 patients with
      comparable condition used traditional craniotomy (control group). The mean time
      of operation, average days in hospital, expenditure and prognosis of two groups
      were recorded and analyzed. RESULTS: There was no significant difference in
      therapeutic efficacy between two groups. Patients in treatment group had a
      shorter hospital stay and less expenditure than those in control group.
      CONCLUSION: Mini-invasive negative pressure drainage is simple, effective,
      economical and applicable to some traumatic EDH patients.

PMID- 17535642
TI  - Repair of acutely injured spinal cord through constructing tissue-engineered
      neural complex in adult rats.
AB  - OBJECTIVE: To construct tissue-engineered neural complex in vitro and study its
      effect in repairing acutely injured spinal cord in adult rats. METHODS: Neural
      stem cells were harvested from the spinal cord of embryo rats and propagated in
      vitro. Then the neural stem cells were seeded into polyglycolic acid scaffolds
      and co-cultured with extract of embryonic spinal cord in vitro.
      Immunofluorescence histochemistry and scanning electron microscope were used to
      observe the microstructure of this complex. Animal model of spine semi
      transection was made and tissue-engineered neural complex was implanted by
      surgical intervention. Six weeks after transplantation, functional evaluation and
      histochemistry were applied to evaluate the functional recovery and anatomic
      reconstruction. RESULTS: The tissue-engineered neural complex had a distinct
      structure, which contained neonatal neurons, oligodendrocytes and astrocytes.
      After tissue-engineered neural complex was implanted into the injured spinal
      cord, the cell components such as neurons, astrocytes and oligodendrocytes, could
      survive and keep on developing. The adult rats suffering from spinal cord injury
      got an obvious neurological recovery in motor skills. CONCLUSIONS: The tissue
      engineered neural complex appears to have therapeutic effects on the functional
      recovery and anatomic reconstruction of the adult rats with spinal cord injury.

PMID- 17535643
TI  - Diagnosis and treatment of 34 cases of blunt duodenal injuries.
AB  - OBJECTIVE: To summarize the experience on diagnosis and treatment of blunt
      duodenal injuries, and thus to improve the therapeutic skills. METHODS: Clinical
      data of 34 cases of blunt duodenal injuries admitted to our hospital from 1990 to
      2006 were retrospectively analyzed. RESULTS: Among them, 28 cases were cured, 20
      cases presented with complications, and 6 cases died. The causes of death were:
      duodenal or pancreatic fistula in 2 cases, intra-and retroperitoneal infection
      complicating septicopyemia in 2, disseminated intravascular coagulation in 1 and
      multiple organ failure in 1. CONCLUSIONS: Misdiagnosis and missed diagnosis
      predispose to happen for blunt duodenal injuries. Early recognition and surgical
      intervention are critical to a successful rescue.

PMID- 17535644
TI  - Polymyxin B antagonizing biological activity of lipopolysaccharide.
AB  - OBJECTIVE: To investigate the mechanism of polymyxin B (PMB) antagonizing the
      biological activity of lipopolysaccharide (LPS). METHODS: The affinity of PMB for
      LPS and lipid A was assayed by biosensor, and the neutralization of PMB for LPS
      (2 ng/ml) was detected by kinetic turbidimetric limulus test. The releases of TNF
      alpha and IL-6 in murine peritoneal macrophages a (PMphi) after exposure to LPS
      (100 ng/ml) were detected, and the expression levels of TLR4, TNF-alpha and IL-6
      mRNA in PMphi induced by LPS (100 ng/ml) were measured by RT-PCR. RESULTS: PMB
      had high-affinity to LPS and lipid A with dissociation equilibrium constants of
      18.9 nmol/L and 11.1 nmol/L, respectively, and neutralized LPS in a dose
      dependent manner. Furthermore, PMB could markedly inhibit the expressions of
      TLR4, TNF-alpha and IL-6 mRNA and the release of cycokines in LPS-stimulated
      murine peritoneal macrophages. CONCLUSIONS: PMB neutralizes LPS and inhibites the
      expression and release of cycokines in macrophages, in which the affinity of PMB
      for lipid A plays an important role.

PMID- 17535645
TI  - Specific inferior dislocation of the hip: one case report.

PMID- 17535646
TI  - Corticosteroids for fat embolism after multiple fractures.

PMID- 17535647
TI  - [Association between genetic polymorphisms of DNA repair genes XRCC1, XRCC3 and
      susceptibility to chronic benzene poisoning].
AB  - OBJECTIVE: To explore the association between genetic polymorphisms of DNA repair
      genes XRCC1, XRCC3 and susceptibility to chronic benzene poisoning. METHODS: A
      case-control study was conducted. Eighty patients with chronic benzene poisoning
      and 62 workers occupationally exposed to benzene who were engaged in the same
      working time and job title as patients were investigated. Polymerase chain
      reaction-restriction fragments length polymorphism (PCR-RFLP) was used to detect
      the single nucleotide polymorphisms on C26304T, G27466A, G28152A, G36189A of
      XRCC1 and C18067T of XRCC3. The relationship between them and latency of chronic
      benzene poisoning was analyzed by Kaplan-Meier method. RESULTS: A correlation for
      XRCC3 18067C/T compared with C/C genotype was found (OR=0.233, 95% CI 0.085
      approximately 0.639, P=0.0046). Patients who were XRCC1 27466G/G homozygous wild
      genotype developed chronic benzene poisoning average 6 years later than those had
      homozygous (27466A/A) or heterozygous (27466G/A) mutant alleles. CONCLUSION:
      Subjects with XRCC3 18067T variant allele are tolerance sub-group to benzene
      poisoning. Patients carrying XRCC1 27466 G/G genotype develop chronic benzene
      poisoning later.

PMID- 17535648
TI  - [Changes of nitric oxide and nitric-oxide synthase in the development of cold
      induced hypertension].
AB  - OBJECTIVE: To study the changes of nitric oxide(NO) and nitric-oxide
      synthase(NOS) in the development of cold-induced hypertension (CIH). METHODS:
      Sixty male Sprague-Dawley adult rats were used. Thirty were exposed to cold (4 +/
      1) degrees C as cold-treated group while the other 30 were at (25 +/- 1) degrees
      C as controls, 4 hours a day for 6 weeks for both groups. Systolic blood pressure
      (SBP) and heart rate were measured twice every week. Each group was further
      subdivided into three groups, 10 rats each. A subgroup of the cold-treated and
      control rats were sacrificed at 2, 4 and 6 week. Plasma was saved to measure
      superoxide dismutase (SOD) and malondiadehycle (MDA), while heart was homogenated
      to measure NO, NOS. RESULTS: 1 SBP increased during 6 weeks of exposure to cold.
      From the second week, SBP of cold-treated group [(94.16 +/- 3.81) mm Hg] was
      significantly greater than that of control group [(88.77 +/- 4.45 mm Hg),
      P<0.01]. The highest SBP level was achieved at the sixth week [(116.78 +/-
      3.79)mm Hg, P<0.01]. 2 Compared to the control group, SOD in cold-treated group
      decreased significantly from the second week, and maintained throughout the time
      of exposure to cold (P<0.05). MDA levels did not differ significantly between
      cold-treated and control groups though it increased mildly during 6 weeks of cold
      exposure (P>0.05). Heart NOS in cold-treated group decreased significantly from
      the fourth week to the sixth week. And a mild decrease was observed in heart NO
      of cold-treated group during 6 weeks of exposure (P>0.05). CONCLUSION: Cold
      induced hypertension is induced in rats after repeated exposure to cold. The
      levels of NOS, NO decrease accordingly to the rise of blood pressure. This
      indicates that the dysfunction of NO and NOS is involved in the development of
      CIH.

PMID- 17535649
TI  - [Response of electroencephalography to isometric exercise-induced local muscle
      fatigue].
AB  - OBJECTIVE: To explore the response of electroencephalography (EEG) signal to
      biceps brachii fatiguing induced by sustained isometric (non-maximal) voluntary
      contraction (non-MVC) and to lay a foundation for effective and reliable fatigue
      evaluation system and for understanding fatigue mechanisms. METHODS: Ten male
      undergraduates performed two different isometric fatiguing tasks with the elbow
      flexion muscles under a load of 5 and 10 kg respectively, and synchronously EEG
      signals were collected from scalp. Then amplitude, spectral and Lempel-Ziv
      complexity C(n) of EEG were calculated. RESULTS: The average EEG(AEEG) increased
      while the average mean power frequency (MPF) and complexity of EEG decreased in
      muscle fatigue. Furthermore, this phenomenon was distributed evenly across the
      entire scalp, but load only influenced AEEG, MPF and C(n) at Fz. CONCLUSION: AEEG
      of EEG increases generally while MPF and C(n) increase generally during local
      muscle fatigue. This pattern of EEG reflects the central mechanism of muscle
      fatigue. AEEG, MPF and C(n) at prefrontal area show load dependence.

PMID- 17535650
TI  - [Effects of high power microwave exposure on cholinergic neurotrophic factors
      protein in rabbit retina].
AB  - OBJECTIVE: To investigate the changes of cholinergic neurotrophic factors (CNTF)
      protein at different time points and the distribution of CNTF in rabbit retina
      after exposure to high power microwave (HPM), in order to determine the changes
      rule of CNTF protein. METHODS: The rabbits were irradiated by HPM (peak power 90
      W/cm(2)) for 15 min respectively, and then killed at 0, 3, 6, 12, 24 and 72 h
      after irradiation. The changes of CNTF protein were investigated by
      immunohistochemistry and semi-quantity analysis. RESULTS: CNTF protein was
      distributed in full retinal layers, special in the cell membrane and cytoplasm.
      HPM irradiation could immediately down-regulated CNTF protein expression at 0 h,
      up-regulated and arrived at peak level at 6 h (P<0.05 vs 0 h group), and then
      kept control level. CONCLUSION: HPM may cause acute retinal injure and change the
      expression of CNTF protein in rabbit retina. These effects show the time
      dependent feature. These results suggest that CNTF activation plays a central
      role in the retinal injures induced by HPM, and supplies a therapy method by
      using foreign-aid CNTF to remedy the retinal injure induced by HPM.

PMID- 17535651
TI  - [Effects of different dose microwave radiation on protein components of cultured
      rabbit lens].
AB  - OBJECTIVE: To study the effects of different dose microwave radiation on protein
      components of cultured rabbit lens, and analyze the mechanisms of lens injury
      caused by microwave radiation. METHODS: Cultured rabbit lens were exposed to
      microwave radiation with frequency of 2450 MHz and power density of 0.25, 0.50,
      1.00, 2.00, 5.00 mW/cm(2) for 8 hours in vitro. The transparency of lens was
      observed. Changes of protein concentration were detected after different lens
      protein components were extracted, including water-soluble protein (WSP), urea
      soluble protein (USP), alkali soluble protein (ASP) and sonicated protein (SP).
      The influence of microwave radiation on WSP was analyzed using SDS-PAGE
      electrophoresis and coomassie-blue staining. RESULTS: Transparency of lens
      decreased after radiation. There was obvious opacification of lens cortex after
      5.00 mW/cm(2) microwave radiation for 8 hours. After 1.00, 2.00 and 5.00 mW/cm(2)
      radiation, the percentage of WSP decreased while USP increased obviously. There
      was no change of ASP. The percentage of SP decreased when the power of microwave
      was 5.00 mW/cm(2). The low molecular weight protein of WSP decreased while high
      molecular weight protein increased after microwave radiation. CONCLUSION:
      Microwave radiation higher than 1.00 mW/cm(2) can affect the proportion of WSP
      and USP in cultured rabbit lens, and cause changes of lens transparency and
      refractive power, which leads to lens opacity.

PMID- 17535652
TI  - [Influence of microwave radiation on synaptic structure and function of
      hippocampus in Wistar rats].
AB  - OBJECTIVE: To investigate the effect of microwave radiation on synaptic
      structure, characteristic of synaptosome, the contents and release of
      neurotransmitters in hippocampus in Wistar rats. METHODS: Wistar rats were
      exposed to microwave radiation with average power density of 30 mW/cm(2).
      Electron telescope was used to study the change of the synaptic structure at 6 h
      after radiation and to identify synaptosome. Flow cytometry and electron spin
      resonance were used to study the change of the concentration of Ca(2+) in synapse
      and the fluidity of membrane proteins of synaptosome. High performance liquid
      chromatography (HPLC) and spectrophotometer were used to study the changes of
      contents and release of amino acids and acetylcholine in hippocampus. RESULTS:
      Microwave radiation of 30 mW/cm(2) caused deposits of synapse vesicle, elongation
      of active zone, the increase of thickness of postsynaptic density (PSD) and
      curvature, and perforation of synapse. The concentration of Ca(2+) in synapse
      (P<0.01) and tc of membrane proteins (P<0.01) of synaptosome increased contents
      of glutamic acid and glycine (P<0.01) and release of GABA increased the increase
      of contents and release of acetylcholine, and activity of acetyl cholinesterase
      (P<0.01) increased. CONCLUSION: Microwave radiation can induce the injure of
      synaptic structure and function of hippocampus, and then induce the disorder of
      the ability of learning and memory in rats.

PMID- 17535654
TI  - [Relationship between social support and occupational stress].
AB  - OBJECTIVE: To explore the relationship between social support and occupational
      stress. METHODS: A cross-sectional survey involving 654 career people from
      different industries was conducted. Social support, the occupational stressors,
      personalities, and occupational strain were measured by using Occupational Stress
      Instrument. RESULTS: The people from different occupations got different level of
      social support. Social support scores were significantly positively related to
      interpersonal relation, responsibility for people, responsibility for thing,
      advancement and participation, task identity, training adequacy, challenge,
      autonomy, job satisfaction, mental health, affective ambulance, positive emotion,
      self-esteem and coping strategy (P<0.05 or P<0.01), negatively to careers, role
      conflict, role ambiguity, job future ambiguity, negative emotion, depression
      symptoms, daily life stress and work locus of control scores (P<0.05 or P<0.01).
      The scores of interpersonal relation, responsibility for people, responsibility
      for thing, advancement and participation, task identity, training adequacy,
      challenge, autonomy, job satisfaction, mental health, affective ambulance,
      positive emotion, self-esteem and coping strategy with sufficient social support
      were significantly higher than those of deficient social support (P<0.05 or
      P<0.01). The scores of role conflict, role ambiguity, job future ambiguity,
      negative emotion, depression symptoms, daily life stress and work locus of
      control were higher than those of the latter (P<0.05 or P<0.01). Stepwise
      regression analysis showed that social support was the predictor of depression
      (R(2)>0.05). CONCLUSION: Social support affects occupational stress largely and
      plays an important role in maintaining mental health of career people. The people
      from different occupations get different level of social support.

PMID- 17535653
TI  - [Effects of electromagnetic irradiation on glucocorticoid in serum and its
      receptor expression in rat hippocampus].
AB  - OBJECTIVE: To explore the role and mechanism of glucocorticoid (GC) in the
      harmful bio-effects of electromagnetic irradiation. METHODS: Rats were exposed to
      65 mW/cm(2) electromagnetic wave for 20 min. At 10 min, 30 min, 3 h, 12 h after
      irradiation, their learning and memory abilities were tested by Morris water
      maze. The levels of corticosterone (CORT) in serum were measured by
      radioimmunoprecipitation assay and the changes of total glucocorticoid receptor
      (GR) expression and GR nuclear translocation in rat hippocampus were measured by
      reverse transcription-polymerase chain reaction and Western blot. RESULTS: The
      rats had learning and memory deficits at 10 min, 30 min and 3 h after
      irradiation, but at 12 h had no difference from the normal control. The levels of
      corticosterone in serum increased significantly at 10 min, 30 min, decreased at 3
      h and increased significantly compared with 12 h after irradiation. GR mRNA and
      total GR protein expression in rat hippocampus had no significant changes at 10
      min, 30 min after irradiation. At 3 h, 12 h GR mRNA expression significantly
      decreased by 69%, 76% respectively and GR total protein decreased by 58%, 67%
      respectively. There were significant differences between the two groups and the
      corresponding controls (P<0.05). And compared with the control, the GR nuclear
      translocation increased significantly at 3 h and 12 h (P<0.05). CONCLUSION: GC
      may take part in the injury to learning and memory abilities after
      electromagnetic irradiation, and the non-genomic and genomic effects of GC may
      play a major role in the early and late stage, respectively.

PMID- 17535656
TI  - [Changes of T lymphocyte subsets in workers with long-term benzene exposure].
AB  - OBJECTIVE: To observe the changes of T-lymphocyte subsets in workers with long
      term benzene exposure, and further understand the benzene's lymphotoxicity.
      METHODS: Blood was sampled from 44 patients with chronic benzene poisoning of
      different degrees, (mild 22 patients, moderate 14, severe 8) respectively. Twenty
      two health benzene exposed workers, and 94 health unexposed workers served as
      normal control. A total of the phenotype (CD4, CD8) of T lymphocyte in peripheral
      blood was analyzed by indirect immunofluorescence assay. RESULTS: Lymphocyte
      subset analysis showed significantly decreased CD4(+) T lymphocytes,
      CD4(+)/CD8(+) ratio, except CD8(+) T lymphocytes in benzene exposed groups
      (P<0.05). Among the four benzene-exposed groups, CD4(+) T lymphocytes and
      CD4(+)/CD8(+) ratio showed no difference (P>0.05). CONCLUSION: The primary
      changes of T-lymphocyte subsets in workers following benzene long-term exposure
      are the decrease of CD4(+)%, but the changes are not correlated with
      haematopoietic injury.

PMID- 17535657
TI  - [Effects of occupational noise exposure on norepinephrine in peripheral blood and
      cardiovascular system].
AB  - OBJECTIVE: To study the effects of noise on bioactivity of norepinephrine (NE)
      and cardiovascular system. METHODS: A total of 130 workers exposed to the
      occupational noise in one enterprise were selected as noise exposure group, and
      134 workers not exposed to the occupational noise and other poisons served as
      control group. Fasting venous blood was drawn to determine the content of NE in
      peripheral blood with ELISA. According to Occupational Health Surveillance Manage
      regulations, the occupational noise exposures crowd was examined. RESULTS: The
      average of NE in exposure group was (0.1387 +/- 0.099) ng/ml, and (0.1019 +/-
      0.080) ng/ml in control group. There was significant difference in NE between
      exposure and control group. There was significant difference in the detection
      rate of BP, HR and ECG between exposure and control group. CONCLUSION: The
      occupation noise can increase the NE in peripheral blood, and maybe affects the
      cardiovascular system in this way.

PMID- 17535677
TI  - [Potential significance of tumor stem cells in tumorigenesis and therapeutics for
      cancer].

PMID- 17535659
TI  - [Changes of serum cytokine caused by acute paraquat poisoning].
AB  - OBJECTIVE: To observe the change of cytokine interleukin IL-1 beta, IL-6, IL-10,
      tumor necrosis factor-alpha (TNF-alpha) occurred in acute paraquat (PQ) poisoning
      rats and to investigate the mechanism of acute lung injury caused by paraquat
      (PQ) poisoning. METHODS: All 72 healthy adult Wistar rats were random assigned
      into normal control groups, paraquat high dose group (120 mg/kg), paraquat middle
      dose (60 mg/kg) group, paraquat low dose group (30 mg/kg). Three observing
      periods of time included 8, 24, 72 h and the standards of TNF-alpha, IL-1 beta,
      IL-6, IL-10 were determined. RESULTS: Every index of the PQ group was
      significantly higher than that in the NS group at the same period of time (P<0.05
      or P<0.01). In the 72 h group, the high dose group was significantly higher than
      the middle and low dose group (P<0.05), and there was no significantly difference
      between the middle and low dose group (P>0.05). For the comparison of index in
      the same dose group, the group of 72 h was much higher than 8 h group and 24 h
      group (P<0.05), and there was no difference between the 8h group and 24 h group
      (P>0.05). CONCLUSION: The cytokine may play an important role in paraquat-induced
      acute lung tissue injury.

PMID- 17535678
TI  - [Emphasis on neuropathologic study of intractable epilepsy].

PMID- 17535679
TI  - [Focal cortical dysplasia with refractory epilepsy: clinicopathologic study of 38
      cases].
AB  - OBJECTIVE: To investigate the clinicopathologic features of focal cortical
      dysplasia (FCD) in patients with refractory epilepsy. METHODS: The clinical,
      radiologic and pathologic features of 38 cases of FCD receiving surgical
      treatment in 2005 were reviewed retrospectively. RESULTS: The mean age of disease
      onset was 9.2 years. The disease lasted for 11.9 years on average and often
      presented as complex partial seizure. Radiologic examination revealed hippocampal
      sclerosis, or abnormal signals in the grey matter in 21 cases. According to
      Palmini's classification system, the following pathologic subgroups were
      identified: FCD type IA (3/38), FCD type IB (20/38), FCD type IIA (5/38) and FCD
      type IIB (5/38). The remaining 5 cases were classified as mild cortical
      dysplasia. Topographically, FCD type II was often seen in the extratemporal
      region (8/10), predominantly in the frontal lobe (5/8). Dual pathology was
      identified only in cases with FCD type IB. Immunohistochemical study showed that
      the giant neurons, immature neurons and dysmorphic neurons were strongly positive
      for NeuN. A small number of balloon cells expressed nestin. CONCLUSIONS: FCD is a
      common cause of refractory epilepsy. FCD type IB is the predominant pathologic
      subtype. Associated hippocampal sclerosis is sometimes seen. Clinicopathologic
      differences between FCD type I and FCD type II are observed.

PMID- 17535680
TI  - [Unusual expression and molecular mechanisms of E-cadherin, beta-catenin in
      correlation with clinicopathologic parameters in neuroblastoma].
AB  - OBJECTIVE: To study the expression of E-cadherin and beta-catenin in
      neuroblastomas of various degrees of differentiation, and to investigate their
      molecular mechanisms in correlation with clinicopathologic parameters. METHODS:
      Immunohistochemistry EnVision method was used to detect E-cadherin and beta
      catenin expression in 90 paraffin-embedded tissue samples of neuroblastomas. The
      methylation status of CpG islands of E-cadherin promoter was investigated by MSP
      in 7 fresh tissue and 24 paraffin-embedded tissue samples. The mutation status of
      exon 3 of beta-catenin gene was studied by PCR in 7 fresh tissue samples.
      Statistical analysis of the data was performed by SPSS software. RESULTS: E
      cadherin and beta-catenin were abnormally expressed in neuroblastomas in general.
      The expression of beta-catenin in well-differentiated neuroblastoms was markedly
      higher (47/70, 67.1%) than that of the poorly differentiated tumors (8/20,
      40.0%). There was a markedly decreased expression of both genes in tumors with
      lymph node metastasis than those without. Demethylation was seen in some regions
      of the promoter of E-cadherin in 31 cases of nuroblatomas. PCR of the exon 3 of
      beta-catenin followed by DNA sequencing demonstrated rearrangements and mutations
      in 7 cases, including 2 cases harboring identical point mutation at gene position
      27184, leading to a T-->A alteration. CONCLUSIONS: The abnormal over-expression
      of E-cadherin in neuroblastomas is independent of the methylation status of their
      promoter sequences. The abnormal expression of beta-catenin may be related to
      mutational changes at exon 3 of the gene.

PMID- 17535681
TI  - [Clinicopathologic analysis of 92 cases of pancreatic cystic neoplasm].
AB  - OBJECTIVE: To study the clinicopathologic and immunohistochemical features of
      cystic neoplasms of the pancreas. METHODS: Ninety-two cases of cystic neoplasm of
      pancreas were retrieved from the Department archival file during the period from
      1999 to 2005. Histologic features were studied and the tumors were typed
      according to WHO classification. Immunohistochemistry was also carried out using
      paraffin-embedded tissues. RESULTS: The age of patients ranged from 16 to 80
      years. The patients included 33 males and 59 females. The tumors varied from 2 cm
      to 21 cm in diameter. They consisted of intraductal papillary mucinous neoplasm
      (36/92), serous cystic neoplasm (18/92), solid pseudopapillary tumor (18/92),
      mucinous cystic neoplasm (14/92), cystic pancreatic ductal adenocarcinoma (4/92)
      and cystic pancreatic endocrine neoplasm (2/92). Immunohistochemical study
      revealed variable staining patterns, with frequent overlaps between different
      tumor types. In general, serous cystic neoplasm expressed MUC1, while mucinous
      cystic neoplasm was positive for MUC-5AC, intraductal papillary mucinous neoplasm
      for MUC-2 and cystic pancreatic ductal adenocarcinoma for MUC-1. On the other
      hand, solid pseudopapillary tumor expressed alpha-antitrypsin, alpha
      antichymotrypsin, vimentin and progesterone receptor. CONCLUSIONS: Accurate
      diagnosis of pancreatic cystic neoplasms requires correlation of clinical
      findings, radiologic examination, histologic features and immunostaining results.
      Pathologic distinction is important because of different prognostic significance.
      Two-thirds of pancreatic cystic neoplasms are premalignant or malignant and
      warrant surgical resection, whereas the remaining one-third (including pseudocyst
      and serous cystadenoma) are benign and can be treated conservatively.

PMID- 17535682
TI  - [Clinicopathologic study of renal cell carcinoma with rhabdoid features].
AB  - OBJECTIVE: To study the clinicopathologic features and biologic behavior of renal
      cell carcinoma (RCC) with rhabdoid features. METHODS: Ten cases of RCC with
      rhabdoid features collected during the period from 1995 to 2005 were enrolled
      into the study. The clinical findings were analyzed and the hematoxylin and eosin
      stained sections were reviewed. Immunohistochemistry and electron microscopy were
      also performed. RESULTS: The age of patients ranged from 33 to 69 years (mean age
      = 52 years). Nine of the patients were males and 1 female. Five patients showed
      evidence of perinephric invasion. Two patients presented with regional lymph node
      metastases and 1 patient showed distant metastasis to the lung. Histologically,
      the rhabdoid foci were characterized by loosely cohesive trabeculae, acini,
      lobules and clusters of rhabdoid cells in otherwise clear cell RCC (9 cases) or
      papillary RCC (1 case). The rhabdoid cells were round to polygonal in shape and
      contained globular eosinophilic inclusion bodies in the cytoplasm, eccentric
      nuclei, vesicular chromatin pattern and prominent nucleoli. Coagulative tumor
      necrosis was commonly seen. Immunohistochemical study showed that the rhabdoid
      cells were diffusely positive for CD10 (10/10), cytokeratin AE1/AE3 (10/10),
      epithelial membrane antigen (10/10) and vimentin (10/10). Focal staining for
      neuron-specific enolase and S-100 protein was also noted. They were negative for
      CK7, CK20 and myogenic markers (including myogenin, smooth muscle actin and
      muscle-specific actin). The mean Ki-67 labeling index of the rhabdoid component
      was higher than that of the non-rhabdoid component (P < 0.05). Follow-up
      information was available in 8 patients. While 6 patients are still alive without
      recurrence, 2 patients died of the disease 6 and 29 months respectively after the
      operation. CONCLUSIONS: RCC with rhabdoid elements are mainly observed in clear
      cell RCC and need to be distinguished from oncocytic renal tumors and malignant
      rhabdoid tumor of kidney. The higher proliferative activity in the rhabdoid areas
      may indicate more aggressive biologic behavior.

PMID- 17535683
TI  - [Clinicopathologic features of membranous nephropathy coexisting with IgA
      nephropathy].
AB  - OBJECTIVE: To study the clinicopathologic features of membranous nephropathy
      coexisting with IgA nephropathy. METHODS: The renal biopsies performed in Peking
      University First Hospital during the period from January, 1998 to April, 2006
      were retrospectively reviewed. The clinicopathologic features of 11 cases of
      membranous nephropathy coexisting with IgA nephropathy were studied. Electron
      microscopy with immunogold labeling for IgG and IgA were also performed. RESULTS:
      The mean age of patients was 39.9 years. The male-to-female ratio was 1:2.9. The
      patients mainly presented with proteinuria. Proteinuria of nephrotic level was
      seen in 7 cases (63.6%). Seven cases also had associated microscopic hematuria.
      None of them showed evidence of renal insufficiency. Cases with secondary
      diseases, such as hepatitis virus infection and systemic lupus erythematosus,
      were excluded from the study. Histologically, vacuolation and thickening of
      glomerular basement membrane was seen. There was also mild mesangial
      hypercellularity and increase in mesangial matrix. Occasional glomeruli with
      crescent formation were identified in 2 cases. Immunofluorescence study showed
      granular staining for IgG and C3 along glomerular capillary walls, in addition to
      clumps of IgA deposits in mesangium. Electron microscopy revealed subepithelial
      and mesangial electron-dense deposits. Immunogold labeling showed IgG and IgA
      localized in the subepithelial and mesangial deposits respectively. CONCLUSION:
      Membranous nephropathy coexisting with IgA nephropathy possesses the
      clinicopathologic features of both components. It might be caused by independent
      occurrence of the two entities.

PMID- 17535684
TI  - [Expression of centromere protein A in hepatocellular carcinoma].
AB  - OBJECTIVE: To study the expression of centromere protein A (CENP-A) and its
      significance in hepatocellular carcinoma (HCC) and adjacent non-neoplastic liver
      tissue. METHODS: The expression levels of CENP-A mRNA in 20 samples of HCC and
      adjacent non-neoplastic liver tissue were analyzed by reverse transcription
      polymerase chain reaction (RT-PCR) and real-time quantitative polymerase chain
      reaction (qRT-PCR). Immunohistochemical study for CENP-A and p53 proteins was
      also performed on tissue microarrays containing 80 samples of HCC and adjacent
      liver tissue. RESULTS: The expression level of CENP-A mRNA in HCC (0.64 +/- 0.18)
      was higher than that in adjacent non-neoplastic liver tissue (0.09 +/- 0.09) (t =
      12.78, P < 0.01). Of the 80 samples of HCC, 57 cases (71.25%) and 60 cases (75%)
      expressed CENP-A and p53 proteins respectively. The positivity rates of CENP-A
      and p53 proteins in non-neoplastic liver tissue were 43.75% (35/80) and 16.25%
      (13/80) respectively. There was a statistically significant difference in CENP-A
      and p53 protein expression between HCC and non-neoplastic liver tissue (P <
      0.01). The coincident rate between CENP-A and p53 expression was 88.75% (71/80).
      Expression of CENP-A protein showed a positive correlation with that of p53
      protein (r = 0.57, P < 0.01). CONCLUSION: The over-expression of CENP-A occurs at
      transcriptional level and may be related to malignant proliferation of HCC via
      possible interaction with p53 gene.

PMID- 17535685
TI  - [Activation of CXCR4 in human glioma stem cells promotes tumor angiogenesis].
AB  - OBJECTIVE: To isolate, culture and identify glioma stem cells from human
      malignant glioma cell line U87, and investigate the changes of pro-angiogenic
      factors production by glioma stem cells followed by activation of CXCR4 and
      observe their tumorigenesis as well as the expression of vascular endothelial
      growth factor when implanted into nude mice. METHODS: The ratio of CD133 positive
      cells was detected by flow cytometry. Magnetic separation of CD133 positive cells
      was carried out on the magnetic cell sorting system (MACS). Expression of nestin,
      glial fibrillary acidic protein (GFAP) and CXCR4 on tumorspheres was detected by
      indirect immunofluorescence under confocal laser scanning microscopy. The
      functional activation of CXCR4 was assessed by calcium mobilization experiments.
      ELISA was used to detect the production of vascular endothelial growth factor
      (VEGF) and interleukin-8 (IL-8) in conditioned medium. Glioma stem cells were
      implanted into nude mice to assess their tumorigenesis ability and the expression
      of VEGF. RESULTS: The ratio of CD133 positive cells with stem cell property was
      0.5% in U87 cells. Activation of CXCR4 on glioma stem cells induced calcium
      mobilization and increased VEGF and IL-8 protein secretion. CD133 positive cells
      secreted more VEGF and IL-8 than their negative counterparts in vitro. Tumors
      derived from CD133 positive cells grew more rapidly and expressed elevated level
      of VEGF than their negative counterparts. CONCLUSIONS: There are a small fraction
      of glioma stem cells in human glioblastoma cell line U87. Expressing functional
      CXCR4 and secreting more pro-angiogenic factors may be involved in tumor
      angiogenesis mediated by glioma stem cells.

PMID- 17535686
TI  - [Influence of beta-amyloid protein and cholesterol on the pathological changes of
      Alzheimer's disease and expression of nicotinic acetylcholine receptors in rats].
AB  - OBJECTIVE: To study the influence of beta-amyloid protein (Abeta) and cholesterol
      on the pathological changes of Alzheimer's disease (AD) and on the expression of
      nicotinic acetylcholine receptor (nAChR) subunits in the brains of rats. METHOD:
      The rats were treated by intracerebroventricular injection of Abeta1-42 and fed
      with a diet containing 5% cholesterol to establish animal model of AD. The
      pathological changes, learning and memory, and expression of nAChRs of rats were
      analyzed by Bieoschowsky staining, immunohistochemistry, water-labyrinth, Western
      blot, and RT-PCR. RESULTS: Abeta intracerebroventricular injection induced Abeta
      deposition in rat brains and high-cholesterol diet resulted in
      hypercholesterolemia in the animals. Injection of Abeta caused a reduction of
      learning and memory of rats and modifications of the expression of nAChRs.
      Cholesterol enhanced these effects of Abeta on neuropathology and expression of
      nAChRs. CONCLUSIONS: Abeta can induce marked neuropathological changes, influence
      the learning and study ability, and modify the expression of nAChRs. Cholesterol
      can enhance the neurotoxicity of Abeta.

PMID- 17535687
TI  - [Suppression of osteosarcoma in vitro by coexpression of antisense VEGF165 cDNA
      and thymidine kinase gene].
AB  - OBJECTIVE: To investigate the effect of VEGF expression in osteosarcoma cell line
      and the target killing effect of HSV1-TK/GCV system on transfected osteosarcoma
      cells under hypoxia conditions. METHODS: Eukaryotic expression plasmid with HRE
      promoter was constructed to express the antisense VEGF165 cDNA and Hygromycin
      phospho-transferase-thymidine kinase (HyTK) fusion gene. The recombinant vectors
      were then transfected into osteosarcoma cell line MG63 with lipofectin mediated
      gene transfer methods. PCR and RT-PCR were used to confirm the presence and
      expression of TK gene. The sensitivity of transfected cells to GCV and "bystander
      effect (BSE)" of HSV1-TK/GCV system under normoxia or hypoxia conditions were
      measured by MTT assay and mixed co-culture experiment. The expression of VEGF
      protein was detected by ELISA under hypoxia condition. Cell cycle phase
      distribution was determined by flow cytometry. In addition, electromicroscopy was
      used to document ultrastructural alterations. RESULTS: The eukaryotic expression
      vector pBI-HRE-AsVEGF165 -HyTK was constructed successfully. The transfected cell
      line MG63TV was established and confirmed by PCR and RT-PCR of the presence of
      transgene and its mRNA expression. GCV was toxic to transfected cells in a
      concentration-dependent manner. The sensitivity to GCV toxicity was 100 times
      higher under hypoxia condition than that under normoxic condition. The mixed
      culture experiments showed that the "bystander effect" was enhanced significantly
      under hypoxia condition. VEGF expression of transgene cells under hypoxia
      condition decreased 50% compared to that of normal condition. Under hypoxia and
      GCV, DNA synthesis of MG63TV cells was inhibited along with an increase of cells
      at G0 approximately G1 phase, apoptosis and necrosis. CONCLUSIONS: Antisense VEGF
      expression driven by HRE promoter in combination with hypoxia can provide a
      target inhibition of VEGF expression in human osteosarcoma cells, with an
      enhanced selective killing effect and BSE of the HSV-TK/GCV system. The double
      gene co-expression system in study provides experimental basis for therapy
      against osteosarcoma by a synchronous antiangiogenic and suicide gene approach.

PMID- 17535689
TI  - [Expression of cyclin-dependent kinase CDC2 and its significance in malignant
      progression of gliomas].

PMID- 17535690
TI  - [Expression of p57Kip2 and its significance in the classification and
      differential diagnosis of hydatidiform moles and hydropic abortions].

PMID- 17535691
TI  - [Pathologic features of renal allografts in 60 cases with deranged renal
      function].

PMID- 17535692
TI  - [Updates on study of glioma stem cells].

PMID- 17535693
TI  - [Roles of gap junctions in tumorigenesis].

PMID- 17535694
TI  - [Classification of precursor lesions for squamous cell carcinoma of uterine
      cervix: updates and controversies].

PMID- 17535695
TI  - [Effect of formalin clearance reagents on tissue samples].

PMID- 17535696
TI  - [Silver impregnation and double immunostaining for alpha-smooth muscle actin and
      ED-1].

PMID- 17535697
TI  - [Intravascular large B-cell lymphoma of brain: report of a case].

PMID- 17535698
TI  - [Primitive neuroectodermal tumor of kidney: report of a case].

PMID- 17535699
TI  - [Malignant glomus tumor of bone: report of a case].

PMID- 17535701
TI  - [Ethical and legislative perspectives on liver transplantation in Mainland
      China].

PMID- 17535703
TI  - [Declaration of the 2nd Meeting of the Committee on Clinical Application of Human
      Organ Transplantation of China and National Summit of Clinical Application and
      Management of Human Organ Transplantation].

PMID- 17535704
TI  - [Actuality and progression of pancreas-kidney transplantation].

PMID- 17535705
TI  - [Technology of living donor liver transplantation in Mainland China].

PMID- 17535706
TI  - [Clinical study of adult to adult living donor liver transplantation: a report of
      56 cases].
AB  - OBJECTIVE: To investigate the ways to ensure the safety of donors and recipients
      in adult-to-adult living donor liver transplantation (A-ALDLT). METHODS: From
      January 2002 to September 2006, 56 A-ALDLT were performed in our division,
      including 52 cases of right lobe graft were obtained without medial hepatic vein
      (MHV) and 4 cases of dual grafts (1 case using two left lobes, 3 cases using 1
      right and 1 left lobe). The most common diagnoses were hepatitis B liver
      cirrhosis (62.5%) and hepatocellular carcinoma (30.4%) in recipients. Among them,
      10 cases scored more than 25 with the model of end-stage liver disease (MELD)
      scoring system. Triphasic liver computed tomography were used for reconstruction
      of hepatic vessels and to calculate total liver and right liver volumes in
      donors. Various innovative surgical techniques were adopted too. RESULTS: From
      the 58 living donors, 55 right lobes and 3 left lobes were obtained. The 55 right
      lobe grafts were obtained without medial hepatic vein, weighed 400 approximately
      860 g (median 550 g). The ratio of graft volume to recipient standard liver
      volume ranged from 31.7% to 71.7% (median 45.4%). All donors' remnant liver
      volumes were over 35% of the total liver volume. There was no donor mortality,
      but 7 (12.5%) donors experienced complications. Of the 56 recipients, with a
      follow-up period of 2 approximately 52 months (median 11 months), 15 (26.8%)
      developed complications and 4 (7.2%) died within 3 months post operation. The 1
      year actual survival rate was 92.8%. CONCLUSIONS: When preoperative CT volume
      shows remnant liver volume is greater than 35% of the total liver volume, and
      graft volume to recipient's standard liver volume ratio is over 40%, A-ALDLT
      using right lobe graft is a safe procedure for both donors and recipients,
      otherwise the dual graft liver transplantation should be considered.

PMID- 17535707
TI  - [Adult-to-adult living donor liver transplantation in treating acute liver
      failure using extended right lobe graft].
AB  - OBJECTIVE: To report experience in adult-to-adult living donor liver
      transplantation for acute liver failure using extended right lobe graft. METHODS:
      A 42-year-old male with acute liver failure received adult-to-adult living donor
      liver transplantation using extended right lobe graft. Volumetric analysis with
      computed tomography (CT) revealed that the volume of donor's extended right liver
      with medial hepatic vein (MHV) amounted to approximately 1.3% of the recipient's
      body weight. The donor hepatic vein and recipient inferior vena cava were
      reconstructed and then anastomosed end to side. The portal veins, hepatic
      arteries and bile ducts were anastomosed end-to-end, respectively. RESULTS: The
      operations in donor and recipient were all successful. The donor recovered
      uneventfully. The recipient regained consciousness in 8 hours and got normal
      liver function 14 days after transplantation. On day 16 after transplantation,
      transaminases such as alanine transaminase, aspartate transaminase increased
      expeditiously in the recipient and was controlled effectively with
      methylprednisolone (1000 mg). The recipient and donor has survived for 8 months
      healthily without vascular and bile duct complications. CONCLUSIONS: Adult-to
      adult living donor liver transplantation for acute liver failure using extended
      right lobe graft can achieve superior results when performed by an experienced
      team in hepatectomy and transplantation. This technique extends the success of
      living donor liver transplantation and opens a new donor pool for adults to
      receive a timely graft of adequate function.

PMID- 17535708
TI  - [Clinical study of liver re-transplantation].
AB  - OBJECTIVE: To report experiences of liver re-transplantation. METHODS: The cause
      of re-transplantation, the pre-operative MELD score, timing of re
      transplantation, technical considerations, 1 year survival rate and the causes of
      death of the patients receiving liver re-transplantation in First Central
      Hospital of Tianjin between January 1999 and December 2005 were retrospectively
      analyzed. RESULTS: One year survival rate of re-transplantation was 71.6%. The
      most common cause of hepatic graft failure and subsequent re-transplantation was
      biliary complications (45.5%). The 1 year survival rate of patients with a MELD
      score less than 20 was higher than patients with a score of 20 approximately 30
      and > 30 (83.8% versus 57.1% and 66.7%). The peri-operative survival rate of
      patients who received re-transplantation 30 days after the initial
      transplantation was higher than those who received re-transplantation between 8
      to 30 days post the first operation (83.8% versus 41.7%). The main cause of peri
      operative death was celiac infections (accounted for 54.2% deaths) in the
      patients. CONCLUSIONS: Proper indication selection, optimum operation time, right
      surgical procedure, intensified peri-operative monitoring and infection control
      are all crucial for the improvement of survival rate in patients receiving liver
      re-transplantation.

PMID- 17535709
TI  - [Study of surgical procedures of abdominal organ cluster transplantation].
AB  - OBJECTIVE: To evaluate the surgical procedures and therapeutic effect of organ
      cluster transplantation in treating abdominal multiple organ malignant tumors.
      METHODS: Two patients with abdominal multiple organ malignant tumors received
      organ cluster transplantation in May and August 2004. The excised specimen
      included liver, pancreas, duodenum, stomach, spleen, mesenteric and epigastric
      lymph nodes. The transplanted organs included liver, pancreas, duodenum. Superior
      mesenteric artery was involved in the malignancy in one case and was transected
      and anastomosed to right common iliac artery. RESULTS: The patients waked up 4
      and 5 hours post operation and began recovering 3 and 5 days after. Dynamic
      examinations showed that the functions of grafted liver, pancreas and duodenum
      obtained normal function in 10 days post the transplantation. One patient
      survived for 12 months postoperatively and died of recurrence of cancer; The
      other recovered uneventfully after transplantation, and discharged automatically
      20 days after. CONCLUSIONS: Abdominal organ cluster transplantation is
      technically feasible and effective for patients with abdominal multiple organ
      malignant tumors.

PMID- 17535710
TI  - [Clinical analysis of infectious complications following abdominal cluster
      transplantation].
AB  - OBJECTIVE: To investigate the characteristic and management of postoperative
      infection in abdominal cluster transplantation. METHODS: Preliminary experience
      of two cases of abdominal cluster transplantation including small intestine was
      reviewed. RESULTS: Combination of five immunosuppressive agents based on
      tacrolimus was used. Severe Gram-negative bacillus infections occurred. The
      majority of invasive fungal infections was due to Candida species.
      Cytomegalovirus (CMV) infection increased monocytes and caused eosinopenia and an
      inversion of the CD4(+) to CD8(+) cell ratio in recipient I, and human CMV matrix
      proteins pp71 (CMV-pp71) was detected and identified in bile by PCR.
      Microabscesses in liver transplant biopsies were presented. CONCLUSIONS:
      Infectious complications after cluster transplantation were complicated.
      Strategies to optimize the immunity suppression protocol and early diagnosis and
      treatment will be important to reduce infection after abdominal cluster
      transplantation.

PMID- 17535711
TI  - [Application of irradiated allograft vascular in the liver transplantation].
AB  - OBJECTIVE: To study the substitute portal vein by irradiated allograft saphenous
      vein during liver transplantation and investigate the changes in morphology and
      immunology. METHODS: All the recipients were divided into 3 groups
      randomly:irradiated allograft group (n = 11) (group A), fresh allograft group (n
      = 9) (group B) and fresh self-graft group (n = 14) (group C). The number of non
      jam graft vessels in each group was explored at 1st week, 2nd week, 1st month,
      2nd month and 3rd month post-operation. Also, the infiltration of CD(4)(+),
      CD(8)(+) T cells and histological changes in grafted vessels were detected.
      RESULTS: No obvious histological changes were observed in group A, as well as
      under naked eyes. There were 9, 3 and 12 non-jam vessels in group A, B and C and
      there were significant differences between group A and B (P < 0.05). The
      endothelial cells of graft vessels were observed both in group A and C two weeks
      post-operation and covered the graft vessels two months later. There were
      infiltration of lymphocytes and inflammatory cells at early stage, obvious damage
      and no endothelial cells growth in graft vessels in group B. Compared with group
      B, the percentage of CD(4)(+), CD(8)(+) T cells in group A was lower
      significantly, but higher slightly than that in group C. CONCLUSIONS: Irradiated
      allograft saphenous veins have the quality of ideal vascular transplantation
      prosthesis and weak antigenicity at the same time. The changes of CD(4)(+),
      CD(8)(+) T cells after allograft vessels can be detected as immunology index for
      acute immunological rejection.

PMID- 17535712
TI  - [Technology and application of simultaneous pancreas-kidney transplantation with
      modified enteric drainage].
AB  - OBJECTIVE: To report the modified technique and the short-term results of
      simultaneous pancreas-kidney transplantation (SPK) with the enteric drainage (ED)
      of exocrine secretions. METHODS: From June 2000 to August 2006, thirty-eight
      patients with diabetes complicated with uremia underwent SPK. The pancreas graft
      was placed intraperitoneally with exocrine secretions drained into the proximal
      jejunum without Roux-en-Y procedure. The mean cold ischemic times of pancreas and
      kidney were (10 +/- 2.0) h and (7 +/- 2.0) h, respectively. Quadruple
      immunosuppressive therapy with antilymphocyte globulin or anti-CD25 monoclonal
      antibody, tacrolimus, mycophenolate mofetil and steroids was adopted except one
      patient. RESULTS: The 6-month survival rates of patients and grafts were both
      97.4% after transplantation. All patients achieved insulin-free euglycemia at (7
      +/- 6.9) d postoperative except one. For preoperative patients, mean fasting
      insulin and C-peptide values were (9 +/- 8.1) mU/L and (6 +/- 4.5) mU/L. After
      operation, fasting insulin and C-peptide values of patients were (12 +/- 5.8)
      mU/L and (6 +/- 4.7) mU/L, respectively, which peaked to an insulin level of (57
      +/- 43.0) mU/L and a C-peptide level of (11 +/- 6.8) mU/L with stimulation. There
      were eight cases of delayed renal graft function. All other patients achieved
      immediate renal graft function. No graft losses occurred due to leakage or intra
      abdominal infection. The most common surgical complications were wound infection
      (n = 12), enteric anastomostic hemorrhage (n = 5) and perirenal hemorrhage (n =
      2). Three patients (7.9%) had been reoperated for the reasons of intra-abdominal
      hemorrhage and perirenal hemorrhage. CONCLUSIONS: SPK is an effective treatment
      option for selected patients with diabetes mellitus and approaching end-stage
      renal disease. Enteric exocrine drainage by direct side-to-side anastomosis
      (without Roux-en-Y) seems to be a simple and reliable technique.

PMID- 17535713
TI  - [The research of xeno-lymphocytes apoptosis induced by Sertoli cells isolated by
      modified methods in vitro].
AB  - OBJECTIVE: To modify the isolation and culture method of Sertoli cells and
      investigate its' effects on xeno-lymphocytes apoptosis. METHODS: Sertoli cells
      which was isolated from 2 - 4 week-old Sprague Dawley (SD) rats, were
      successfully prepared by collagenase type V, trypsin and DNase I and then
      identified by electron microscope. Viability and apoptosis of cultured cells were
      measured by flow cytometry. The apoptosis rates of Balb/c mouse lymphocytes were
      examined which were co-cultured with Sertoli cells of SD rats by flow cytometry,
      too. The expression of FasL, TGF-beta(1) and clusterin on Sertoli cells were
      detected by immunocytochemistry. RESULTS: In the co-cultured system, Sertoli
      cells accounted for more than 90%. The viability of Sertoli cells was above 95%
      and the apoptosis rate was 10.87% +/- 3.87% in this study. The lymphocytes
      apoptosis ratio was 15.52% +/- 0.17% (P < 0.01). Streptavidin-biotin-peroxidase
      complex immunochemistry staining showed that the Sertoli cells could express
      FasL, TGF-beta(1) and clusterin, respectively. CONCLUSIONS: It indicates that the
      expression of FasL, TGF-beta(1) on the Sertoli cells might relate to the immune
      privilege, and it supposed to be benefit for xenotransplantation.

PMID- 17535714
TI  - [The influence of warm ischemia-reperfusion injury on cell cycle control in
      liver].
AB  - OBJECTIVE: To observe the effect of warm ischemia-reperfusion injury (WIRI) on
      the genes involved in the cell cycle in liver and investigate the molecular
      mechanism of WIRI. METHODS: Twenty-four Sprague-Dawley male rats were divided
      into experiment groups and sham operation group respectively. According to the
      dynamic characteristics, the genes involved in the cell cycle were submitted for
      multivariate cluster and self-organized map analysis. Total RNA was extracted for
      the microarray analysis and subsequent real-time quantitative PCR. RESULTS: There
      were 86, 410, 234 up-regulated genes and 136, 312, 653 down-regulated genes over
      2 - 4 times in the 0 h, 1 h and 24 h group respectively, most of which such as
      Gadd45a, Egr1, Hsp70 were involved in the cell cycle checkpoint, energy
      metabolism, signal transduction, immune-associated procedure, and so on. In
      addition, the results of microarray analysis were confirmed by real-time
      quantitative PCR. CONCLUSIONS: Some genes related with cell cycle and
      regeneration were activated in the early stage of WIRI. Gadd45a, Egr1 and Hsp70
      may be new targets to cure WIRI.

PMID- 17535715
TI  - [The influence of cold preservation on the microcirculation of intrahepatic bile
      duct after liver transplantation].
AB  - OBJECTIVE: To discuss the influence of cold preservation on intrahepatic biliary
      microcirculation. METHODS: Male Sprague Dawley (SD) rats were divided into 3
      groups:cold preserve 1 h group (CP 1 h group), cold preserve 24 h group (CP 24 h
      group) and sham operation group (SO group). Five time points were determined as 0
      h, 1 h, 6 h, 24 h and 72 h postoperation. Morphology was observed under light
      microscope. Dark microspheres were injected into hepatic artery and the number of
      microspheres in liver portal areas was measured under light microscope. The
      expressions of eNOS, ET-1 and ICAM-1 in microvascular endothelial cells of
      hepatic portal area were measured by immunofluorescence double staining technique
      and in situ hybridization histochemistry. RESULTS: The histological changes of
      intrahepatic bile duct were more severe in CP 24 h group than in CP 1 h group.
      The number of microspheres in implanted liver portal areas was increased
      significantly in CP 24 h group than in CP 1 h group at the same time point.
      Compared with CP 1 h group, the expression of eNOS in CP 24 h group significantly
      reduced after liver transplantation, while the expressions of ET-1 and ICAM-1 in
      CP 24 h group were significantly increased after liver transplantation. The
      changes of their mRNA expressions were the approximately same as well as their
      proteins expressions. CONCLUSIONS: Cold preservation brings obvious changes of
      intrahepatic biliary microcirculation and function of vascular endothelial cell
      after liver transplantation. The obstruction of microcirculation might play an
      important role in the reperfusion injury after cold preserve of intrahepatic
      biliary during liver transplantation.

PMID- 17535729
TI  - Molecular insights into uremic cardiomyopathy: cardiotonic steroids and Na/K
      ATPase signaling.
AB  - Patients with chronic renal failure develop a "uremic" cardiomyopathy
      characterized by diastolic dysfunction, left ventricular hypertrophy, fibrosis,
      and systemic oxidant stress. Patients with chronic renal failure also are known
      to have increases in the circulating concentrations of endogenous cardiotonic
      steroids (also referred to as endogenous digitalis-like substances.) Endogenous
      cardiotonic steroids produce reactive oxygen species as part of the signal
      cascade induced by binding to the plasmalemmal Na/K-ATPase in patients, and this
      signal cascade appears capable of inducing several key pathophysiologic features
      of uremic cardiomyopathy. In addition, these patients develop both fibrosis and
      oxidant stress without a known mechanism. In this review we highlight data
      supporting the hypothesis that endogenous cardiotonic steroids are a key
      molecular component involved in the diastolic dysfunction, left ventricular
      hypertrophy, fibrosis, and systemic oxidant stress associated with chronic kidney
      disease.

PMID- 17535730
TI  - Ouabain-dependent signaling in caveolae as a novel therapeutic target for
      hypertension.
AB  - Experimental and clinical evidence indicates that Endogenous Ouabain (EO) and
      Adducin polymorphism play a pathogenetic role in hypertension and related organ
      complications. These effects occur through a complex interaction of genetic
      molecular mechanisms regulating renal sodium reabsorption and vascular function.
      The activation of a Na-K ATPase-Src-EGFr-ERK signaling pathway within the
      restricted membrane subdomains of caveolae by Ouabain has been associated to
      hypertension and cardiac remodeling. Rostafuroxin (PST 2238) is a novel anti
      hypertensive compound able to selectively antagonize EO/Ouabain and Adducin
      hypertensive effect and Ouabain-induced cardiac hypertrophy in rats. Studies have
      been conducted in vivo and in a cell-free system to prove that Rostafuroxin
      exerts its antihypertensive and antihypertrophic effects by antagonizing the Src
      dependent signaling triggered by Ouabain. At the vascular level, Rostafuroxin
      antagonizes the Ouabain-mediated increase of myogenic vascular tone. This
      peculiar and novel mechanism of action, together with a good tolerability and
      efficacy both in animal models and hypertensive patients, make Rostafuroxin the
      prototype of a new class of antihypertensive compounds able to antagonize EO/
      Ouabain and Adducin molecular effects.

PMID- 17535731
TI  - Endogenous Na/K-ATPase inhibitors in patients with preeclampsia.
AB  - Although preeclampsia (PE) is a major cause of maternal and fetal mortality, its
      pathogenesis is not fully understood. Digitalis-like cardiotonic steroids (CTS)
      are believed to be involved in the pathophysiology of PE, as illustrated by
      clinical observations that DIGIBIND, a digoxin antibody which binds CTS, lowers
      blood pressure in PE. Recently we reported that plasma levels of marinobufagenin
      (MBG), a vasoconstrictor CTS, are increased fourfold in patients with severe PE.
      In the present study, we tested whether anti-MBG, or anti-ouabain antibodies, or
      DIGIBIND can reverse inhibition of erythrocyte Na/K-ATPase (NKA) from patients
      with mild PE (blood pressure, 149 +/- 3/93 +/- 3 mm Hg; age, 28 +/- 2 years;
      gestational age, 37 +/- 1 weeks). Development of PE was associated with twofold
      rise in plasma MBG levels (1.58 +/- 0.15 vs. 0.80 +/- 0.11 nmol/L; P<0.01). The
      activity of erythrocyte NKA in 12 patients with PE was lower than in 6
      normotensive gestational age-matched subjects (1.56 +/- 0.18 vs. 3.11 +/- 0.16
      micromol Pi/ml/hr; P<0.001). In vitro treatment of erythrocytes from PE patients
      with anti-MBG antibody fully restored the NKA activity (3.26 +/- 0.41 micromol
      Pi/ml/hr; P<0.01). The effects of DIGIBIND was marginally significant (2.53 +/-
      0.32 micromol Pi/ml/hr), while the anti-ouabain antibody was not effective (2.25
      +/- 0.25 micromol Pi/ml/hr, P>0.5). The present observations provide evidence for
      a role for MBG in the pathogenesis of PE, and suggest that antibodies against MBG
      may be useful in the treatment of this syndrome.

PMID- 17535732
TI  - Marinobufagenin in hypertensive patients with obstructive sleep apnea.
AB  - Although obstructive sleep apnea (OSA) is an independent risk factor for
      hypertension, the underlying mechanisms are not clearly understood. Apnea and
      hypopnea episodes during sleep lead to sympathoactivation, decrease plasma pH,
      and predispose to sodium and volume retention. We hypothesized that, the latter
      could stimulate digitalis-like natriuretic/vasopressor hormones, endogenous
      ouabain (EO) and marinobufagenin (MBG). Overnight polysomnography (Embletta) and
      24 hrs blood pressure monitoring (SpaceLab 90207) was conducted in 52 consecutive
      patients with OSA (51 +/- 8 years; 40 males, 12 females) and in 48 age-matched
      hypertensive subjects without OSA. According to the polysomnography data, 17
      patients had a mild degree of OSA (apnea/hypopnea index (AHI) 5-15), 17 patients
      moderate (AHI 15-30) and 18 -severe OSA (AHI >30). Levels of MBG excretion co
      varied with OSA severity (0.5 +/- 0.1, 0.9 +/- 0.04 and 1.2 +/- 0.06 nmoles per
      24 hrs, respectively), while excretion of EO did not differ in patients with
      different degrees of OSA severity. Our observations suggest that MBG may be
      involved in the pathogenesis of hypertension in OSA, and may be a marker of OSA
      severity.

PMID- 17535733
TI  - On the importance and mechanism of amplification of digitalis signal through
      Na+/K+-ATPase.
AB  - Therapeutic concentrations of digitalis drugs inhibit the proliferation of breast
      cancer cells by inducing the interaction of Na+/K+-ATPase with Src/EGFR,
      activation of ERK1/2, and the resulting upregulation of cell cycle inhibitor
      p21Cip1. Quantitative comparison of ouabain dose-response curves for growth
      arrest and pump inhibition shows that ratio of Ki (pump)/Ki (proliferation) =
      7.2. Such large gains in sensitivity are characteristic of several signal
      transducing pathways of other receptors. Making the reasonable assumption that
      Na+/K+-ATPase is the only receptor for ouabain, the large amplification factor
      clearly shows that occupation of a small fraction of pumping Na+/K+-ATPase by
      digitalis drugs, or endogenous digitalis-like factors, is sufficient to cause
      near complete inhibition of cell growth. The likely causes of large amplification
      factor in the signaling function of Na+/K+-ATPase include (a) interactions among
      the protomers of Na+/K+-ATPase in the membrane; and (b) induced clustering of
      Na+/K+-ATPase oligomers with neighboring proteins. The upstream location of both
      mechanisms suggests that similar amplifications also occur in other cell types
      with different digitalis downstream effects; e.g., stimulation of proliferation
      or hypertrophy.

PMID- 17535734
TI  - Na+,K+-ATPase and hormone ouabain:new roles for an old enzyme and an old
      inhibitor.
AB  - Na+,K+-ATPase and its specific inhibitor ouabain entered the 21st century with an
      entirely new set of properties, that are the focuses of the present review. (i)
      The adhesive property of the beta-subunit explains why is Na+,K+-ATPase expressed
      polarizedly on one side of epithelial cells, a crucial property to explain the
      exchange of substances between higher organisms and the environment; (ii) Ouabain
      was recently recognized to be a hormone. (iii) Na+,K+-ATPase is known to act as a
      receptor for hormone ouabain, (iv) binding of ouabain to the Na+,K+-ATPase
      modifies adhesion: at high concentrations the outcome is total detachment. (v)
      Ouabain-resistant cells and ouabain-sensitive ones establish a special type of
      cell-cell interaction, so that sensitive cells withstand the presence of
      otherwise lethal levels of ouabain. (vi) Hormone ouabain provokes relocalization
      of specific molecules from the submembrane scaffold to the nucleus, where these
      bind to promoters of genes involved in proliferation, differentiation, migration,
      etc. (vii) Finally, ouabain causes a retrieval of Na+,K+-ATPase from the plasma
      membrane. We speculate that this would reduce the driving force that operates co-
      and counter-transporters, which are responsible for the exchange of substances
      across epithelia.

PMID- 17535735
TI  - Identification of protein kinase C as an intermediate in Na,K-ATPase beta-subunit
      mediated lamellipodia formation and suppression of cell motility in carcinoma
      cells.
AB  - We have shown that repletion of Na,K-ATPase Beta1-subunit (Na,K-Beta) in Moloney
      Sarcoma virus transformed MDCK (MSV-Na,K-Beta) cells induced lamellipodia and
      suppressed motility in a PI3-Kinase dependent manner. In this study, we provide
      evidence that decreased cell motility is due to increased attachment of Na,K-Beta
      expressing cells to the substratum. Treatment of MSV-Beta-GFP cells with
      bisindolylmalemide, a general Protein Kinase C (PKC) inhibitor, abolished PI3
      Kinase activation and its down stream effects of Rac1 activation, binding of Na,K
      Beta to annexin II, and suppression of cell motility and attachment. Thus, these
      studies unraveled that a PKC is involved upstream of PI3-Kinase in the
      suppression of Na,K-Beta mediated cell motility in carcinoma cells.

PMID- 17535736
TI  - Metabolic and signaling events mediated by cardiotonic steroid ouabain in rat
      skeletal muscle.
AB  - The cardiac glycoside ouabain initiates a cascade of signaling events through
      Na+,K+-ATPase, leading to an increase in cell growth and proliferation in
      different cell types. We explored the effects of ouabain on glucose metabolism in
      skeletal muscle and clarified the mechanisms of ouabain signal transduction. In
      rat soleus muscle 200 microM ouabain decreased basal glucose uptake without
      effect on insulin-stimulated glucose uptake. Ouabain increased glycogen synthesis
      additively to insulin and this effect was abolished in the presence of a MEK1/2
      inhibitor (PD98059) or a c-Src inhibitor (PP2). Ouabain exposure reduced glucose
      oxidation, and this effect was reversed in the presence of PP2. Incubation with
      ouabain did not affect intramuscular ATP and its metabolites; however acetyl-CoA
      carboxylase phosphorylation was reduced, with no effect on AMPK phosphorylation.
      Insulin-stimulated Akt phosphorylation was not affected by ouabain. Ouabain
      reduced basal and insulin-stimulated phosphorylation of PKC alpha/beta and delta
      isoforms, whereas phosphorylation of PKCzeta was unchanged. Ouabain exposure
      increased interaction of 1- and 2-subunits of Na-pump with c-Src, as assessed by
      co-immunoprecipitation with c-Src. Phosphorylation of ERK1/2, GSK 3 / and p90rsk
      activity was increased in response to ouabain, and these effects were prevented
      in the presence of PD98059 and PP2. In conclusion, the cardiac glycoside ouabain
      stimulates glycogen synthesis additively to insulin in rat skeletal muscle. This
      effect is mediated by activation of c-Src-, ERK1/2- p90rsk- and GSK3-dependent
      signaling pathway.

PMID- 17535737
TI  - Signalling pathways involving sodium pump stimulate endothelin-1 secretion and
      nitric oxide production in endothelial cells.
AB  - The cardiac steroid ouabain, a known inhibitor of the sodium pump, or Na+,K+
      ATPase, has been shown to induce a variety of signaling cascades in various
      cells. The present study addresses the question of which signaling pathways are
      activated by ouabain in endothelial cells. Our findings indicate that ouabain,
      applied to human umbilical artery endothelial cells (HUAECs) in culture at low
      concentrations that do not cause global sodium pump inhibition, induces a
      reaction cascade that leads to the release of the vasoactive peptide endothelin-1
      (ET-1). While ouabain-induced ET-1 release seems to be accomplished within 10
      min, ouabain also stimulates a second signaling cascade that involves activation
      of Akt (also known as protein kinase B, or PKB), activation of endothelial nitric
      oxide synthase (eNOS) and increased NO production in HUAECs. This reaction
      cascade reaches its maximum approximately 30 min after exposure to the steroid.
      The results indicate that ouabain or similar compounds might actively participate
      in the regulation of vascular tone.

PMID- 17535738
TI  - Vascular endothelium as a target for endogenous ouabain: studies on the effect of
      ouabain on human endothelial cells.
AB  - It has been suggested that an endogenous inhibitor of the sodium pump, identified
      as ouabain, contributes to the regulation of blood pressure and the pathogenesis
      of certain forms of hypertension. Vascular endothelial cells, whose functional
      integrity is crucial for the maintenance of blood flow and the antithrombotic
      activity, could be a target for endogenous ouabain. We studied the effect of
      ouabain on human umbilical vein endothelial cells (HUVEC) and found that
      nanomolar concentrations of the glycoside have an antiapoptotic activity that is
      dependent on the activation of phosphatidylinositol 3 kinase (PI-3K) and
      extracellular signal-regulated kinases (ERKs). At the same concentrations we
      found that ouabain affects the endocytosis of 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide (MTT) through the activation of signaling proteins
      such as Src kinase. This review sumarizes our findings on the effect of ouabain
      on HUVEC, the signal transduction pathways involved and the significance of these
      observations on the pathophysiology of endothelial function.

PMID- 17535739
TI  - The rapid decline of MTT reduction is not a marker of death signaling in ouabain
      treated cells.
AB  - Decreased staining with dimethylthiazol diphenyltetrazolium (MTT) is widely used
      for cell death detection. This study examined MTT assay as a marker of the
      Na+i,K+i-independent mode of cell death revealed in ouabain-treated C7-MDCK cells
      derived from distal tubule of the Madin-Darby canine kidney. The action of 3-M
      ouabain on MTT reduction in C7-MDCK cells exhibited bipartite kinetics with a
      rapid ~2-fold decline occurring in 30-120 min and a delayed ~8-10-fold decrease
      after 10 hr of ouabain addition. Treatment with ouabain for 18 hr led to 6-fold
      activation of caspase-3, 4-fold elevation of chromatin fragmentation, and massive
      cell detachment. Caspase-3 activation, chromatin fragmentation and cell
      detachment were completely abolished by acidification of the incubation medium
      from pH 7.2 to 6.7. In contrast, the 2-fold inhibition of MTT reduction seen in 5
      hr of ouabain addition was not affected by medium acidification. Within the 5-hr
      time window, we did not observe any significant impact of ouabain on the cellular
      redox state estimated by the autofluorescence ratio of reduced pyridine
      nucleotides and oxidized flavoproteins. In rat aortic endothelial cells and
      primary astrocytes, exposure to 5-mM ouabain attenuated MTT reduction but did not
      affect cell survival. Thus, our results show that diminished staining with MTT in
      ouabain-treated cells is not sufficient proof of triggering of the cell death
      machinery. We speculate that altered endo- and exocytoses evoked by cardiotonic
      steroids contribute to decreased MTT reduction.

PMID- 17535740
TI  - Short-term effects of cardiac steroids on intracellular membrane traffic in
      neuronal NT2 cells.
AB  - Cardiac steroids (CS) are specific inhibitors of Na+, K+-ATPase activity.
      Although the presence of CS-like compounds in animal tissues has been
      established, their physiological role is not clear. In a previous study we showed
      that in pulse-chase membrane-labeling experiments, long term (hours) interaction
      of CS at physiological concentrations (nM) with Na+, K+-ATPase, caused changes in
      endocytosed membrane traffic in human NT2 cells. This was associated with the
      accumulation of large vesicles adjacent to the nucleus. For this sequence of
      events to function in the physiological setting, however, CS would be expected to
      modify membrane traffic upon short term (min) exposure and membrane labeling. We
      now demonstrate that CS affects membrane traffic also following a short exposure.
      This was reflected by the CS-induced accumulation of FM1-43 and transferrin in
      the cells, as well as by changes in their colocalization with Na+, K+-ATPase. We
      also show that the CS-induced changes in membrane traffic following up to 2 hrs
      exposure are reversible, whereas longer treatment induces irreversible effects.
      Based on these observations, we propose that endogenous CS-like compounds are
      physiological regulators of the recycling of endocytosed membrane proteins and
      cargo in neuronal cells, and may affect basic mechanisms such as neurotransmitter
      release and reuptake.

PMID- 17535741
TI  - Hypokalemia potentiates ouabain's effect on calcium cycling and cardiac growth.
AB  - We have previously noted that in neonatal myocytes grown in culture, reductions
      in extracellular K+ concentration produced a hypertrophic response as assessed by
      induction of early response genes, atrial natriuretic peptide and skeletal actin
      and repression of the alpha 3 isoform of the sodium pump in a dose dependent
      manner. Similarly, decreases in media K+ concentration caused increases in
      cytosolic calcium concentration in a dose dependent manner, which correlated with
      repression of alpha 3 expression. In the current study we demonstrate that
      decreases in media K+ concentration caused increases in cytosolic calcium
      concentration in isolated adult rat cardiac myocytes. These increases are
      potentiated by the addition of the cardiotonic steroid, ouabain and blocked by
      the addition of the Src kinase inhibitor Herbimycin A. In parallel studies
      performed in vivo, when rats subjected to dietary K+ restriction were
      subsequently subjected to partial (5/6th) nephrectomy for 4 weeks, cardiac growth
      was greater than in rats fed a control diet. These data suggest that hypokalemia
      may produce phenotypic alterations consistent with cardiac hypertrophy as well as
      potentiate the cardiovascular effects of cardiotonic steroids.

PMID- 17535742
TI  - Modulation of neural activities by Na, K-ATPase alpha 2 subunit through
      functional coupling with transporters.
AB  - Na,K-ATPase is the active transporter that maintains Na+ and K+ gradients across
      the cell membrane. The enzyme is composed of Alpha and Beta subunits and there
      are four Alpha and three Beta subunit isoforms. The enzyme is responsible for
      various physiological processes including housekeeping function of animal cells,
      and specific function has been allocated to each isoform during evolution. We
      found that the Na,K-ATPase Alpha2 subunit functions in concert with various
      transporters during ontogeny by analyses of phenotypes of mice with defective
      Alpha2 subunit. The homozygous mice die soon after birth without breathing and
      the heterozygous mice show late-onset obesity. We summarize here the specific
      functions of the Na,K-ATPase Alpha2 subunit and physiological roles in vivo.

PMID- 17535743
TI  - Na/K-ATPase endocytosis couples pumping and leaking activities in renal
      epithelial cells: a hypothesis.
AB  - Renal adaptation to acute or chronic volume expansion as well as dietary sodium
      intake involves a marked decrease in proximal tubule sodium transport. The
      precise molecular mechanisms involved in this alteration in proximal tubule
      sodium transport are still unclear. Low concentration of ouabain, a cardiotonic
      steroid (CTS) that is a specific inhibitor as well as a ligand of the Na/K
      ATPase, has been shown to significantly inhibit transepithelial Na+ transport
      without altering the intracellular Na+ concentration ([Na+]i) in LLC-PK1 cells.
      This process is mediated by ouabain-activated signaling pathways that stimulate
      the endocytosis of the basolateral Na/K-ATPase and down-regulation of apical NHE3
      (Na/H exchanger isoform 3). Thus, we propose that CTS, such as ouabain and
      marinobufagenin (MBG), are intimately involved in renal proximal tubule
      adaptations to volume expansion. We further speculate that CTS-induced Na/K
      ATPase endocytosis couples pumping and leaking activities in renal epithelial
      cells.

PMID- 17535744
TI  - TRPP2: Ca2+-permeable cation channel and more.
AB  - TRPP2 (polycystin-2) is a member of the TRP family of non-selective cation
      channels that is mutated in human autosomal polycystic kidney disease. It is
      thought to function together with polycystin-1 (PKD1), a large plasma membrane
      integral protein, as part of a multiprotein complex involved in transducing Ca2+
      dependent mechanosensitive information in renal epithelial cells. TRPP2 has been
      implicated in Ca2+-dependent pathways in a variety of biological functions and
      species, including cell proliferation, sperm fertilization, mating behavior and
      asymmetric gene expression. Although its function as a Ca2+-permeable cation
      channel is well established, its precise role, regulation and subcellular
      localization in plasma membrane, endoplasmic reticulum and cilium have remained
      controversial. The present review summarizes the most pertinent recent evidence
      regarding the structural and functional properties of TRPP2 channels, focusing on
      the regulation and physiology of mammalian TRPP2.

PMID- 17535747
TI  - Regulation of cell growth mediated by the calcitonin receptor.
AB  - Calcitonin (CT) is a 32 amino acid peptide hormone of thyroidal origin, whose
      main recognised physiological role is the inhibition of osteoclast--mediated bone
      resorption. There is also evidence that CT might modulate bone formation.
      However, both CT and its receptors (CTR) have also been identified in a large
      number of other cell types and tissue sites, suggesting roles for the CT/CTR
      system distinct from those involving calcium homeostasis. Evidence has
      accumulated consistent with the involvement of CT in cell growth and
      differentiation and in tissue development and remodelling. The close proximity of
      cells expressing CT, or CT receptors (CTR), during development, and during
      pregnancy and lactation, is consistent with important roles for CT in
      morphogenesis. It thus appears that, in tissues such as the uterus, breast and
      pituitary, CT acts in a paracrine manner to Influence cell proliferation and
      function, as distinct from its endocrine actions to regulate calcium stores in
      the skeleton. In vitro studies have shown that CT can be either mitogenic or can
      inhibit cell proliferation, depending on the cell type and the conditions of the
      experiment. More recently, evidence has also been obtained for a role for CT in
      cell survival, in cells as diverse as osteoblast--like and osteocyte--like cells,
      osteoclasts and neurons.

PMID- 17535745
TI  - The NHE1 Na+/H+ exchanger regulates cell survival by activating and targeting
      ezrin to specific plasma membrane domains.
AB  - NHE1 is a ubiquitously expressed Na+/H+ exchanger, which is important for vital
      cell functions. Using in vivo models of kidney podocyte injury and renal tubular
      epithelial cell (RTC) culture systems, we previously demonstrated that NHE1
      defends against apoptosis by a mechanism involving ezrin binding to the NHE1
      cytoplasmic domain. We now extend the NHE1 role to diabetic mouse models and
      refine the mechanism of NHE1-dependent ezrin activation. Streptozotocin induced
      diabetes resulted in greater azotemia, albuminuria and tubulointerstitial
      pathology in NHE1-deficient swe/swe compared to wild-type control mice. Increased
      RTC apoptosis was noted in swe/swe mice, suggesting that loss of NHE1 function
      leads to tubular atrophy, which predicts kidney disease progression. In vitro,
      proximal RTC derived from swe/swe mice also underwent increased apoptosis in
      response to staurosporine or a hypertonic environment. Activated ezrin normally
      resides in the apical domain of the proximal RTC, while NHE1 is a basolateral
      protein. After NHE1 activation by intracellular acidification or extracellular
      hypertonicity, confocal immunofluorescence microscopy in polarized LLC-PK1 cells
      demonstrated transient ezrin localization to lateral membrane domains, where it
      is positioned to interact with NHE1. We conclude that cell stresses promote NHE1
      ezrin interaction, which activate cell survival pathways to prevent apoptosis in
      diabetic and non-diabetic kidney diseases.

PMID- 17535748
TI  - Expression and cellular localization of calcitonin receptor: RT-PCR and in situ
      hybridization studies.
AB  - Calcitonin receptor (CTR) has been identified in bone, kidney and brain, but
      precise tissue distribution and cellular localization remain to be established.
      In this study, we carried out in situ hybridization (ISH) analysis of CTR in rats
      and found intensive signals in exocrine glands, including salivary gland,
      exocrine pancreas and fundic glands of the glandular stomach, and epithelia of
      the seminal vesicle and prostatic glands. On the other hand, no signals were seen
      in the mesenchymal tissue including muscle, and connective and hematopoietic
      tissues. RT-PCR analysis showed that both CTR isoforms, C1a and C1b, were
      expressed in the central nervous system, only C1a isoform in the digestive,
      respiratory, urinary, reproductive and endocrine systems, and neither isoform in
      the mesenchymal tissue and hematopoietic tissues. These results showed that
      expression of CTR isoforms varies among various tissues, suggesting that CT
      functions through different mechanisms.

PMID- 17535749
TI  - Cytosine-adenine repeat polymorphism at calcitonin gene locus associated with
      serum osteocalcin level in Japanese women.
AB  - Bone mineral density and the serum concentration of osteocalcin are influenced by
      multiple genetic factors, including hormone and genes. Our aim was to evaluate
      the correlation between the dinucleotide (cytosine (C)-adenine (A)) repeat
      polymorphism at the calcitonin locus and bone mineral density and serum
      osteocalcin levels. Sixty-six healthy Japanese women over 50 years of age were
      included in this study. The bone mineral density of the second to fourth lumbar
      vertebrae was measured using dual-energy X-ray absorptiometry and serum
      osteocalcin was measured using an immunoradiometric assay. We isolated DNA from
      peripheral leukocytes and genotyped the cytosine-adenine repeats at the
      calcitonin locus using the polymerase chain reaction. We found that bone mineral
      density was not correlated with the number of cytosine-adenine repeats. However,
      the circulating osteocalcin level was significantly different among the different
      cytosine-adenine repeat groups. The osteocalcin level of the 10/17 (C-A)
      heterozygote group was significantly lower than those of the other groups
      (p<0.01). The 10/17 (C-A) and 17/17 (C-A) genotypes are common in the Japanese
      population, and the osteocalcin levels of the 10/17 heterozygotes were
      significantly lower than those of the 17/17 homozygote (p<0.05). Our findings
      suggest that the cytosine-adenine repeat at the calcitonin gene locus may be one
      of the genetic factors that regulate serum osteocalcin levels in Japanese women.

PMID- 17535750
TI  - Signal transduction pathways of calcitonin/calcitonin receptor regulating
      cytoskeletal organization and bone-resorbing activity of osteoclasts.
AB  - Calcitonin is a calcium-regulating peptide hormone that acts directly on
      osteoclasts and suppresses their function. In this review we will focus on the
      downstream signaling pathways of calcitonin receptor regulating cytoskeletal
      organization of osteoclasts. We will also introduce the clinical application of
      the hormone for metabolic bone diseases.

PMID- 17535751
TI  - Effects of calcitonin on the function of human osteoclast-like cells formed from
      CD14-positive monocytes.
AB  - Calcitonin inhibits bone-resorbing activity of osteoclasts. Expression of mRNA of
      calcitonin receptor (CTR) and its related proteins was examined in human
      osteoclasts and their progenitors. CD14-positive (CD14 + macrophages) in the
      monocytes prepared from human peripheral blood cells differentiated into
      macrophages (CD14 +) presence of macrophage colony-stimulating factor (M-CSF) or
      into osteoclast-like cells (OCLs) in the presence of M-CSF plus receptor
      activator of NFkappaB ligand. CD14 macrophages expressed mRNA of CTR-like
      receptor (CRLR), receptor activity modifying protein (RAMP) 1, RAMP2, and RAMP3,
      but not CTR. In contrast, OCLs expressed mRNA of CTR but not CRLR or RAMPs. Human
      OCLs cultured on dentine slices formed actin rings (corresponding to clear zones)
      and resorption pits on the slices. Calcitonin disrupted actin rings and inhibited
      the pit-forming activity of OCLs. CTR is known to couple to cAMP-dependent
      protein kinase (PKA) and protein kinase C (PKC). The effect of calcitonin on
      actin ring disruption was partially blocked by adding H-7, an inhibitor of both
      PKA and PKC. Both forskolin, an activator of PKA, and phorbol myristate, an
      activator of PKC, disrupted actin rings in OCLs. These results suggest that both
      PKA- and PKC-mediated signals are involved in calcitonin-induced inhibition of
      human OCL function.

PMID- 17535752
TI  - Molecular physiology and pharmacology of calcitonin.
AB  - Calcitonin is a thirty-two amino acid peptide that contains an N-terminal
      disulphide bridge and a C-terminal prolineamide residue. It is released from
      thyroid parafollicular C-cells and its direct actions on the osteoclast account
      for its physiological effects whether as a hypocalcaemic agent and a potent
      inhibitor of bone resorption. These effects likely reflect actions upon a number
      of specific osteoclast cell surface receptors that initiate intracellular
      signaling events through both cyclic AMP and calcium mediated second messenger
      pathways. Studies of its potent anti-resorptive effects have significant
      translational implications in the management of Paget's bone disease,
      osteoporosis, and hypercalcaemia. This chapter summarizes major concepts in the
      synthesis and structure of calcitonin and then proceeds to outline its cellular,
      molecular actions and therapeutic applications, whilst seeking to provide a
      reference source. More detailed accounts have been given on different aspects of
      calcitonin physiology and biochemistry in a number of recent reviews by ourselves
      and others (155,157, Zaidi et al., 1994; 2002).

PMID- 17535753
TI  - Role of free radicals and antioxidants in health and disease.

PMID- 17535754
TI  - [Aortic valve sparing for aortic root aneurysm in patients with Marfan syndrome].

PMID- 17535755
TI  - [New instruments, same risks].

PMID- 17535756
TI  - [Medium-term changes in myocardial perfusion and ventricular remodeling following
      acute myocardial infarction].

PMID- 17535757
TI  - [Aortic valve preservation in Marfan syndrome. Initial experience].
AB  - INTRODUCTION AND OBJECTIVES: Preservation of the aortic valve using the technique
      described by David has been shown to be as effective as the Bentall-De Bono
      procedure. It avoids both the need for long-term anticoagulation and the
      complications associated with mechanical prostheses. We report our initial
      experience using this technique in patients with Marfan syndrome. METHODS:
      Between April 2004 and April 2006, we used the David reimplantation technique in
      40 patients with an aortic root aneurysm. Eighteen patients had Marfan syndrome.
      Their median age was 29 years (13-55 years). Echocardiography showed that the
      median diameter of the aortic sinus was 53 mm (46-59 mm). RESULTS: In 17
      patients, aortic valve preservation was possible. No patient died during
      hospitalization and there were no significant complications. On echocardiography
      at discharge, no patient had greater than grade-II aortic regurgitation. During a
      median follow-up period of 8 months (1-24 months), one patient died due to
      rupture of an abdominal aneurysm. The others are all in New York Heart
      Association class I. CONCLUSIONS: Preservation of the aortic valve by means of
      valve reimplantation produced excellent results. It avoided both the
      thromboembolic and hemorrhagic complications associated with prostheses and the
      need for long-term anticoagulation. If reimplanted valves continue to function
      adequately over the long term, this technique should become the treatment of
      choice for aneurysms of the ascending aorta in patients with Marfan syndrome.

PMID- 17535758
TI  - [Calibrating the SCORE cardiovascular risk chart for use in Spain].
AB  - INTRODUCTION AND OBJECTIVES: The Third Joint European Task Force on
      cardiovascular prevention recommended the SCORE function for predicting 10-year
      cardiovascular mortality should be used to guide decision-making on clinical
      interventions. The objective of the present study was to calibrate the function
      for use in Spain. METHODS: A model was developed to apply the hazard ratios for
      cardiovascular mortality at 10 years in SCORE study cohorts to the mean age- and
      sex-specific risk factors found in the third survey of the MONICA-Catalonia study
      (1994-96) and to 10-year cardiovascular survival function for the Spanish
      population based on mortality rates for the year 2002. RESULTS: The estimated
      risks derived using the calibrated SCORE function were 13% higher than those
      estimated using the low-risk algorithm. However, the differences between the two
      varied with age, sex, and, in particular, smoking history. The calibrated SCORE
      risk chart identified 32 high-risk situations that were not registered in the
      original low-risk SCORE chart. However, 50% of these situations had a low or zero
      prevalence. The maximum percentage of subjects who were newly identified as being
      at a high risk using the calibrated chart was 22%. Most differences were observed
      in men aged over 55 years. CONCLUSIONS: While risk estimates based on
      sufficiently large Spanish population cohorts are still not available,
      application of the original cardiovascular risk function calibrated for use in
      Spain should enable the appropriate clinical and public health decisions to be
      taken.

PMID- 17535759
TI  - [Abnormal myocardial perfusion after infarction in patients with persistent TIMI
      grade-3 flow. Only an acute phenomenon?].
AB  - INTRODUCTION AND OBJECTIVES: It has been suggested that abnormal perfusion as
      derived from cardiovascular magnetic resonance imaging (CMR) is a transient
      dysfunction of microcirculation after myocardial infarction (MI) with TIMI 3
      flow. We hypothesized that defects of myocardial perfusion may persist during the
      following months. METHODS: Forty-seven patients with MI and sustained TIMI 3 flow
      underwent intracoronary myocardial contrast echocardiography (MCE) 1 week and 6
      months after infarction. Abnormal perfusion by MCE was regarded as > 1
      hypoperfused segment. RESULTS: At the first week, 20 patients showed abnormal
      perfusion as derived from MCE. At the sixth month 10 patients displayed chronic
      abnormal perfusion. These patients had greater left ventricular volumes and lower
      ejection fraction at the sixth month by CMR (P< .01). CONCLUSIONS: MCE detects
      perfusion defects which can persist in chronic phase--this relates to more severe
      systolic dysfunction and increased left ventricular volumes.

PMID- 17535760
TI  - [Nonbacterial thrombotic endocarditis: clinicopathologic study of a necropsy
      series].
AB  - INTRODUCTION AND OBJECTIVES: Nonbacterial thrombotic endocarditis (NBTE) is
      characterized by sterile platelet and fibrin deposition on cardiac valves. In
      this study, our aim was to investigate the clinicopathologic characteristics of
      patients diagnosed with NBTE at the 12 de Octubre University Hospital in Madrid,
      Spain. METHODS: Patients were identified by analyzing reports of autopsies
      carried out at the Anatomical Pathology Department of the University Hospital
      between 1974 and 1977 and between 1980 and 2004. RESULTS: Out of 2041 autopsies,
      22 (1.08%) showed evidence of NBTE. The patients' average age was 63.04 years,
      and neither sex predominated. The underlying disease was an infection in 54.5% of
      cases, whereas 31.8% had a neoplasm, most frequently a pancreatic adenocarcinoma
      or renal carcinoma. In 10 cases, there was a previous valvulopathy. The mitral
      valve was most frequently affected by NBTE (36.5% of cases). In most cases, the
      cause of death was the underlying disease, though in two patients it was directly
      related to NBTE (9.1%). In nine cases, an embolism occurred, principally in the
      spleen, the kidneys or the central nervous system. Before death, there was no
      suspicion of NBTE in any of these cases. CONCLUSIONS: NBTE is an uncommon disease
      entity that occurs not only in patients with end-stage neoplastic disease, but
      also in those with potentially treatable diseases. Consequently, we should raise
      our level of awareness of this condition so that a diagnosis can be made before
      the patient dies and anticoagulant treatment can be started, thereby helping to
      improve prognosis.

PMID- 17535761
TI  - [The adventitia reduces left ventricular dynamic afterload via smooth muscle
      activation-dependent mechanisms].
AB  - INTRODUCTION AND OBJECTIVES: Ventricular dynamic afterload depends on arterial
      viscoelastic and geometric properties. Vasoactive factors produced in the
      adventitia modulate arterial tone. However, it is still not known whether the
      adventitia is involved in determining the magnitude of the dynamic afterload. The
      aim of this study was to investigate the role played by the adventitia, via
      smooth muscle-dependent mechanisms, in determining dynamic afterload. METHODS:
      The diameter, pressure and flow in brachiocephalic trunks from sheep were
      measured before and after removal of the adventitia, both in vivo with muscular
      reactivity preserved (n=8) and in vitro with muscular reactivity abolished (n=8).
      All studies were performed under similar hemodynamic conditions. Dynamic
      afterload was determined from elastic and viscous arterial responses, elastic and
      viscous work, arterial characteristic impedance, and pulse wave velocity.
      Comparison of in vivo and in vitro findings enabled smooth muscle-dependent
      changes to be evaluated. RESULTS: Only in vivo, did removal of the adventitia
      lead to a reduction in vessel diameter (17.32 [2.02] vs 15.46 [1.28] mm) and to
      increases in elastic (7.21 [1.39] vs 15.59 [3.00] x 10(6) dyn.cm(-2)) and viscous
      (5.16 [2.04] vs 9.87 [2.00] x 10(5) dyn.s.cm(-2)) arterial responses, elastic
      (6.15 [1.08] vs 9.20 [0.76] x 10(-2) J/m2) and viscous work (11.61 [2.25] vs
      15.20 [2.37] x 10(-3) J/m2), impedance (223.97 [136.11] vs 396.33 [182.27] dyn x
      s x cm(-3)), and pulse wave velocity (397.70 [31.21] vs 598.78 [28.04] cm.s(-1))
      (P<.05). The reduction in diameter and the increases in elastic and viscous
      responses are evidence of muscular activation. CONCLUSIONS: The adventitia may
      contribute to the control of ventricular dynamic afterload by means of mechanisms
      dependent on muscular tone.

PMID- 17535762
TI  - [Urinary NT-proBNP level: relationship with ventricular function parameters in
      heart failure].
AB  - INTRODUCTION AND OBJECTIVES: The plasma N-terminal probrain natriuretic peptide
      (NT-proBNP) level is a sensitive marker of ventricular dysfunction. The
      diagnostic and prognostic value of urinary NT-proBNP measurement has been
      demonstrated. The objective of this study was to determine the relationship
      between established parameters of ventricular function and the urinary NT-proBNP
      level. METHODS: The study involved 74 patients with heart failure (54 male, age
      66 [12] years). A Doppler echocardiographic study was performed to measure
      atrioventricular plane displacement (AVPD), ejection fraction, mitral flow
      propagation velocity, and E/A. Urinary and plasma NT-proBNP levels, and the
      plasma aldosterone level were measured. RESULTS: In the whole group, the plasma
      NT-proBNP level was 948 (961) pg/mL, the urinary NT-proBNP level was 88.7 (17.8)
      pg/mL, and the aldosterone level, 165 (145) pg/mL. There were correlations
      between urinary NT-proBNP level and AVPD (r=-0.5; P< .0001), ejection fraction
      (r=-0.3; P< .01), and mitral flow propagation velocity (r=-0.24; P< .05). On
      dividing AVPD and ejection fraction measurements into quartiles, respectively,
      the urinary NT-proBNP levels for these quartiles were Q1: 103 (28) pg/mL, Q2: 89
      (9) pg/mL, Q3: 86 (9) pg/mL, and Q4: 78 (9) pg/mL (P< .0001) and Q1: 101 (26)
      pg/mL, Q2: 85 (12) pg/mL, Q3: 83 (10) pg/mL, and Q4: 85 (11) pg/mL (P< .05),
      respectively. Multiple linear regression analysis showed that the plasma NT
      proBNP level was an independent predictor of the urinary NT-proBNP level (P<
      .0001). When the plasma NT-proBNP level was excluded, AVPD and ejection fraction
      appeared as alternative independent predictors (P< .05). CONCLUSIONS: There is a
      correlation between the urinary NT-proBNP level and left ventricular function
      parameters. This study supports the use of the urinary NT-proBNP level as a
      biochemical marker of ventricular function in heart failure patients.

PMID- 17535763
TI  - [Cardiovascular risk factors in children. Main findings of the Four Provinces
      study].
AB  - Atherosclerosis is a process that begins during the first few decades of life,
      progresses asymptomatically, and generally shows no clinical manifestations until
      adulthood. The Spanish Four Provinces study, which involved 1275 prepubertal
      children, was an investigation into childhood risk factors for atherosclerosis
      (e.g., diet, anthropometric variables, lipid levels, and some genetic factors)
      that may be related to the occurrence of coronary artery disease in adults. In
      this review, we summarize the study's most important findings. The Four Provinces
      study showed that several factors associated with the metabolic syndrome (i.e.,
      obesity, and raised glucose and triglyceride levels), which can lead to coronary
      disease in adults, are already present in schoolchildren. What is more, children
      from provinces with high coronary disease mortality weighed more and had higher
      plasma triglyceride and glucose levels. A high percentage of children in all
      provinces studied had total cholesterol and low-density lipoprotein cholesterol
      plasma levels above the recommended values. Despite the presence of some positive
      features in the population as a whole, such as a raised high-density lipoprotein
      cholesterol level and low prevalence of the apolipoprotein-E epsilon4 allele,
      which is known to be related to cardiovascular risk, if the metabolic changes
      described above persist, the risk of cardiovascular disease in Spain can only
      increase in the future. These metabolic characteristics are associated with a
      high-fat, low-carbohydrate diet which is far from that currently recommended for
      children. Correction of this poor diet at an early age would have significant
      benefits for the prevention of cardiovascular disease.

PMID- 17535764
TI  - [Guidelines on diabetes, pre-diabetes, and cardiovascular diseases].

PMID- 17535765
TI  - [Management of acute aortic syndromes].
AB  - Acute aortic syndrome (AAS) describes the acute presentation of patients with
      characteristic "aortic pain" caused by one of several life threatening thoracic
      aortic conditions including aortic dissection, intramural hematoma or penetrating
      atherosclerotic ulcer. Recent advances in imaging and therapeutic techniques have
      emphasized the importance of early diagnosis of acute aortic syndrome because it
      is crucial for survival. Not just because the cardiovascular community knows
      little, the management of AAS remains a therapeutic challenge, while diverse
      surgical and percutaneous strategies for the treatment of aortic syndromes are
      continuously evolving. As a result of increasing knowledge and better management
      strategies in this area, the outcomes of patients treated for acute aortic
      syndromes have improved. This review discusses the etiology and clinical
      presentation, but mainly focuses on modern management and both established and
      emerging therapeutic approaches to acute aortic syndromes.

PMID- 17535766
TI  - [Transient mid-ventricular ballooning: a variant of Takotsubo syndrome].

PMID- 17535767
TI  - [Predictive value of differential pulse pressure in the diagnosis of silent
      myocardial ischemia in patients with type-2 diabetes].
AB  - Silent myocardial ischemia occurs more frequently in diabetics. Differential
      arterial pulse pressure is a valuable predictor of cardiovascular disease. We
      studied 48 consecutive male patients with type-2 diabetes and no known history of
      ischemic heart disease. Ambulatory monitoring of arterial pressure was carried
      out and the presence of silent myocardial ischemia was studied using a protocol
      that involved: resting ECG, echocardiography, 24-hour Holter ECG, conventional
      exercise stress testing, and exercise testing with nuclear scanning. Nine
      patients (19%) had silent myocardial ischemia. Differential pulse pressure had
      good discriminative ability in identifying the presence of silent ischemia: the
      area under the receiver operating characteristic (ROC) curve was 0.83 (95%
      confidence interval [CI], 0.71-0.96; P=.002). This predictive ability was also
      observed on adjusted logistic regression modeling (odds ratio [OR], 1.24, 95% CI
      = 1.02-1.49). We found that the OR for the risk of silent ischemia for every 10
      mmHg increase in differential pulse pressure was 8.5 (95% CI 1.7-31.2). Age and
      differential pulse pressure were the only independent predictors of silent
      myocardial ischemia found in this study.

PMID- 17535768
TI  - [Transcatheter closure of postinfarction ventricular septal defects using
      Amplatzer devices].
AB  - We carried out transcatheter procedures to close postinfarction ventricular
      septal defects (PIVSDs) in 19 patients: two had recanalization after surgical
      closure, and 17 had a primary PIVSD. In three of the latter patients, who had
      acute PIVSDs, the procedure was carried out in the first 3 weeks after
      infarction; in the 13 patients with subacute PIVSD, it was carried out 3.5-12
      weeks after infarction. There was another procedure in one patient with chronic
      PIVSD. In total, 22 procedures were completed: 17 using an Amplatzer atrial
      septal occluder, two using an Amplatzer postinfarction ventricular septal defect
      occluder, and two using an Amplatzer muscular ventricular septal defect occluder.
      The procedure was successful in 14 patients: in 11 with subacute PIVSD, one with
      chronic PIVSD, and two with postsurgical PIVSD. Transcatheter closure of PIVSDs
      using an Amplatzer atrial septal occluder is probably the treatment of choice in
      patients undergoing surgery more than 3.5 weeks after myocardial infarction and
      in those with recanalization after previous surgical closure.

PMID- 17535769
TI  - [Long-term follow-up of hypertrophic cardiomyopathy patients with implantable
      cardioverter-defibrillators].

PMID- 17535770
TI  - [Percutaneous stent implantation for aortic coarctation in two adults with severe
      left ventricular dysfunction].

PMID- 17535771
TI  - [Reflections on the future of cardiology].

PMID- 17535772
TI  - [The imbalance between supply and demand for cardiologists in Spain].

PMID- 17535774
TI  - Melatonin and thyroxine response to pollution in white stork nestlings (Ciconia
      ciconia): aspects of rhythmicity and age.
AB  - There is growing evidence that ubiquitous environmental contaminants may
      interfere with vertebrate endocrine systems. The selected endocrine biomarkers
      are used to indicate the condition of free-ranging populations of wildlife,
      including avian species. The aim of this study was to determine the impact of
      environment quality on serum thyroxine (T4) and melatonin (Mel) in white stork
      nestlings (Ciconia ciconia) living in different locations: small villages in
      natural areas surrounded by forests and crop fields, near the city and near the
      copper smelter. We extended our analyses to examine the hormones' day-night
      changes in conjunction with chicks' age. Total serum T4 and Mel was measured by
      RIA. T4 level, as a decisive measure of thyroid hormone productivity, was
      significantly lower in the nestlings exposed to pollutants from the copper
      smelter. Mel, as a well-known scavenger of free radicals, was elevated in the
      nestlings in the area near the copper smelter. This study indicates that
      alteration in T4 and Mel levels could be a useful marker of exposure of nestling
      wild storks to different toxic substances in field studies. Mel is postulated to
      be a susceptible defensive molecule as a protective mechanism for organisms.

PMID- 17535775
TI  - Multi-modality nuclear medicine imaging: artefacts, pitfalls and recommendations.
AB  - Multi-modality imaging is rapidly becoming an essential tool in oncology.
      Clinically, the best example of multimodality imaging is seen in the rapid
      evolution of hybrid positron emission tomography (PET)/computed tomography (CT)
      and single positron emission computed tomography (SPECT)/CT scanners. However,
      use of multi-modality imaging is prone to artefacts and pitfalls. Important
      artefacts that may lead to clinical misinterpretation result from the use of CT
      data to correct for attenuation and the existence of mismatches between the fused
      images, for example due to respiratory movement. Furthermore, for institutions
      who proceed from a standalone PET to a hybrid PET-CT, there is an issue of
      interchangeability between these systems, especially for quantitative studies.
      Another issue is visualisation: hospital PACS is not sufficiently capable of
      adequately viewing integrated images. This article reviews and illustrates the
      most common artefacts and pitfalls that can be encountered in multi-modality
      nuclear medicine imaging. For correct management of oncological patients it is
      essential to be able to detect and correctly interpret these artefacts and
      pitfalls. Therefore, solutions and recommendations to these problems are
      provided.

PMID- 17535777
TI  - Laryngeal cancer: how does the radiologist help?
AB  - The radiologist makes a valuable contribution to the staging of laryngeal cancer
      and this has a direct influence on treatment planning. This review focuses on the
      main anatomical concepts, patterns of tumour spread and how to detect this with
      optimal cross sectional imaging. Issues surrounding the relationship of tumour to
      the ventricular complex, submucosal laryngeal spaces, anteroposterior extension,
      laryngeal cartilage involvement and metastatic spread are discussed and
      illustrated. The impact of these imaging findings on the array of therapeutic
      options is described.

PMID- 17535776
TI  - Imaging in genitourinary cancer from the urologists' perspective.
AB  - It is well established that advances in imaging may lead to early cancer
      detection, more accurate tumour staging and consequently adequate treatment,
      better monitoring of the disease and enhanced surveillance for recurrences after
      treatment. This manuscript reviews the current use of imaging in genitourinary
      cancer and explores the impact of imaging findings in clinical management.
      Additionally, an effort has been made to present the emerging imaging modalities
      and also their possible role in diagnosis and treatment of these cancers.

PMID- 17535779
TI  - [Cancer epidemiology after the Chernobyl accident].
AB  - The radioactive fallout from the Chernobyl accident, on 26 April 1986, has caused
      contamination of very wide areas of the northern hemisphere, in particular in
      Europe, causing chronic exposure of millions of people to a mixture of external
      and internal radiation. This paper summarizes the epidemiological studies
      published to date on the risks of cancer following the Chernobyl accident. An
      increase in the incidence of thyroid cancer observed among those exposed in
      childhood and adolescence in the most contaminated territories of Belarus, Russia
      and Ukraine is at present the only scientifically demonstrated radiation-related
      increase in cancer incidence. This observation provided important information on
      the risk of thyroid cancer related to 131I and on factors, such as iodine
      deficiency and stable iodine supplementation, which can modify this risk. The
      reports on increases in the incidence of other types of cancer are difficult to
      interpret because of methodological limitations. As the majority of these studies
      cover a relatively short time period, it is not possible to fully evaluate the
      radiological impact of the accident, and it is premature to draw conclusions on
      the risk of cancers other than that of thyroid. Predictions, based on the
      experience of other populations exposed to ionizing radiation, suggest that a
      substantial number of cancers could occur in Europe, especially in the most
      contaminated areas. Well-focused studies could verify these predictions, in
      particular with regard to the risks of leukaemia among liquidators and breast
      cancer among young women in the most contaminated areas.

PMID- 17535778
TI  - Magnetic resonance imaging of the cervix.
AB  - Due to deficiencies of clinical staging, magnetic resonance (MR) imaging is being
      increasingly used in the pre-treatment work-up of cervical cancer. Lymph node
      status, as evaluated by advanced imaging modalities, is also being incorporated
      into management algorithms. Familiarity with MR imaging features will lead to
      more accurate staging of cervical cancer. Awareness of impact of staging on
      management will enable the radiologists to tailor the report to clinically and
      surgically relevant information. This article emphasizes the guidelines on the MR
      staging criteria, dependence of newer treatments on imaging staging and lymph
      node involvement, and MR imaging in post-treatment surveillance of cervical
      cancer.

PMID- 17535780
TI  - [Neurotrophic theories of stress and neurobiology of antidepressants:
      applications in psycho-oncology].
AB  - For some years, the concept of stress has been accepted as a reference framework
      for the study of disturbances of psychological adjustment to cancer. Stress is
      defined as a state of physiological and psychological << tension >> resulting
      from the interaction between an individual and her environment. Damaging
      consequences of chronic stress include functional and structural alterations of
      the central nervous system, which have to be understood in order to propose
      effective treatment strategies for frequently encountered psychopathological
      responses to cancer. The clinical manifestations of stress include anxious and
      depressive symptoms which can reach pathological intensity under the form of
      major depression and post-traumatic stress disorder. Depression also represents a
      type of post-traumatic stress syndrome. These clinical entities commonly require
      the use of antidepressant treatments. Because of some obstacles, however, studies
      assessing the use and efficacy of antidepressants in oncology remain extremely
      scanty. Furthermore, clinical conditions characterized by drug treatment
      resistance are still uneasily managed due to partial understanding of the fine
      tuned mechanisms of action of antidepressants. A thorough discussion of these
      mechanisms is therefore needed in order to precisely delineate (1) the
      neurobiological bases of the physiopathology of stress and (2) how to extend this
      knowledge to the care of depression in oncology. Maybe more important in this
      respect is the fact that recent scientific data provide a growing support for the
      potential role of psychological variables in the evolution and prognosis of
      cancer. In this paper, we travel back to the origins of antidepressant action
      theories, with the monoaminergic hypothesis, that revealed the role of serotonin
      and norepinephrine in the physiopathology of depression. We will focus on signal
      transduction cascades leading to the expression of genes coding for transcription
      and growth factors (CREB and BDNF). The importance of neuronal atrophy in the
      physiopathology of chronic stress and of neurogenesis in the action of
      antidepressants will also be emphasized. Finally, we present the information
      processing hypothesis, which provides strong support to the use of combined
      treatment strategies, associating psychotherapy and pharmacological approaches in
      the care of severe depression in patients with cancer.

PMID- 17535781
TI  - [Management of clinical stage I testicular germ cell tumours].
AB  - Testicular germ-cell cancer is the most frequent malignancy in young men. In 80%
      of case no metastasis is observed at diagnosis. Orchidectomy is the initial
      therapeutic intervention. In case of a pure seminoma, three treatment options
      should be discussed after surgery : radiotherapy with a limited dose and volume,
      surveillance, and chemotherapy by single-agent carboplatin. In non-seminomatous
      germ cell tumour three options should also be considered : surveillance,
      chemotherapy (two cycles of the BEP regimen) or retroperitoneal lymph node
      dissection. The strategy should be chosen taking into account predictive factors
      of relapse and the patient willing. Whatever the strategy, the cure rate is about
      99%.

PMID- 17535782
TI  - [Place of hand-held gamma camera (POCI) in sentinel node biopsy].
AB  - The main interest in the sentinel node (SN) detection concept has led to the
      development of several prototypes of hand held gamma cameras. After the first
      successful clinical trials with intra-operative imaging probes, the time has come
      to evaluate the potential benefits of these devices. The objective of this review
      was to show the potential interest of a hand-held camera POCI to perform a
      lymphoscintigraphy in order to precisely localize SNs in patients with breast
      cancer.

PMID- 17535783
TI  - [Informed consent or choice? An ethical dilemma in oncology practice].
AB  - How articulate information, mutidisciplinary practice, choice and decision of the
      treatment in a good patient-doctor relationship, an ethical relationship ? Doctor
      is an expert who gets the information (patients have more and more others sources
      of information). Choice of the treatment depends of the facts (the evidence) and
      personal values (the preferences). The selection between the different options
      (most often they are several options) may be done by the physician or by
      physicians in a multidisciplinary clinics, in the presence of the patient or not.
      The final decision to do or not the treatment belongs to the patient (who is not
      always aware of that). Initial sharing of the information between patient and
      doctor may permit the patient to choose himself the best option. More complete is
      sharing of the information, more the patient is able to do a free choice (without
      the influence of the doctor). It is often possible (genetics, prevention,
      screening, adjuvant treatments) to share in full the available information
      (knowing its relativity and limits). In oncology, the full sharing of the
      information is not always realistic, neither asked by the patient. Nevertheless,
      it is possible to go progressively with the patient to a preferred choice through
      a deliberative process, a co-construction of the decision. But often, the doctor
      refer to a pre-established protocol, build by physicians, representing the choice
      of the majority (doctors and/or patients) in the "same" situation. Only one
      option is offered to the patient from whom consent is asked, the information been
      then delivered to explain the choice already done. This paternalistic attitude is
      very effective, comfortable and don't alter the satisfaction of the majority of
      the patients, however, it limits the patient's autonomy. The patient is not
      allowed to choose between all the possibilities but accept or refuse the doctor's
      choice. With the extreme variability of the situations, it would be illusive to
      defend a unique attitude. Doctor has yet to try to adapt himself to every single
      case.

PMID- 17535784
TI  - [Organized cervical cancer screening for underpriviledged women].
AB  - Individual cervical screening with pap-smears is the major cause of the decrease
      in incidence and mortality of cervical cancer in France since more than 30 years.
      But, for the last ten years, the decrease in mortality is limited due to the
      persistence of poor prognostic cases and the insufficiency of treatment efficacy
      in such patients. These cases are mostly observed in women who did not
      participate to regular screening. They are generally from low socioeconomic
      levels or migrant populations, or both. Such an observation leads us to organize
      3 successive pilot campaigns (2001, 2003, 2005) in the Northern part of Marseille
      city where the rate of such poor population is high (37 to 45%). The women
      without a pap-smear indexed in the National Insurance Register for the last 3-2
      years were invited by individual mailing to perform, free of charge, a pap-smear.
      The evaluation of each campaign helps us to improve the next one. The major
      changes from the 1st one to the 3rd one were to increase the number of free
      screening services, to send a second invitation to the non responders, and to
      organize local meetings with social workers and nurses to explain to the women
      the importance of performing regular screening tests. The final results after the
      3 campaigns showed : out of the eligible women the participation rates are
      dramatically low evolving from 1,56 % to 2,48% and 6,87% of pap-smears done along
      the 3 campaigns ; the selection of women "without pap-smear" from the national
      Insurance register was not good, a great number of missing data was identified,
      explaining partly the extremely low rate of participation ; the factors
      increasing a little the participation are the second mailing of invitation (39 %
      of pap-smears realised) ; the total gratuitous of the screening (both sampling
      and reading) ; the oral information delivered locally by social workers and the
      proximity of the places to perform the test ; the quality of the pap-smears
      collected by gynecologists was good but insufficient for other health
      professionals, requiring a specific training for cervical cell collection. The
      organization of such pilot projects need to be followed to find better solutions
      to increase the participation to cervical screening of such populations who are
      at high risk of poor prognosis cervical cancers.

PMID- 17535785
TI  - [HRT in post menopausal women and breast cancer at the Institut Curie].
AB  - Several recent papers have suggested the role of HRT in the development of breast
      cancers. From the data base of the Institut Curie we compared the clinical
      characteristics, histoprognosis factors and survival of a cohort of 6737 patients
      recorded between 1988 and 1999 in which 1482 declared having receive HRT for more
      than 6 months. Surgical procedure, locoregional recurrence, metastasis, disease
      free and global survival were compared bet the patient who received an HRT versus
      the patients who didn't receive this treatment Mammographic diagnosis was more
      frequent in the HRT group and the age at diagnosis was smaller (p < 10(-4)).
      Cancers diagnosed in the HRT group were smaller and had a more favourable
      biologic profile as well as there were more lobular carcinomas and the
      conservative treatment was more frequent (p < 10(-4)). Mean follow up was 97
      months. Recurrence free survival was not different in the two groups but the
      metastasis free and global survival were better in the HRT group. HRT remained an
      independent prognostic factor in a multivariate analysis. In western countries
      the increasing incidence of breast cancer concerns pre as well as post menopausal
      women. HRT cannot be considered as the only responsible of this augmentation.

PMID- 17535786
TI  - [Number and nature of drug interactions concerning antineoplastic drugs].
AB  - Antineoplastic drugs are prone to drug-drug interactions. Cancer patients often
      receive multiple concurrent medications and health care professionals are not
      always aware that patients are also taking others treatments. The aim of this
      study was to assess the number of drug-drug interactions of antineoplastic drugs
      used in solid tumours and to find out and collect recommendations for each of
      them. We performed a bibliographic search from the Vidal dictionary, the
      "thesaurus de l'Afssaps", the "dossier du CNHIM" and from literature of
      scientific journals. For the 40 antineoplastic drugs studied, 726 drug-drug
      interactions were identified; 186 from the Vidal dictionary, 356 from scientific
      literature and 184 from others bibliographic sources. The most frequently
      involved antineoplastic drugs are ifosfamide, paclitaxel and erlotinib. The ATC
      groups of associated drugs are antiinfectives for systemic use, alimentary tract
      and metabolism and nervous system. Antiretrovirals are prone to drug interactions
      with antineoplastic drugs, particularly ritonavir, tipranavir and efavirenz. 7
      contraindications and 15 unadvised associations were held. For 58% of
      interactions, no management recommendation was specified in the bibliographic
      source. Healthcare professionals must be aware that the Vidal dictionary gave
      information for only 26 % of registered drug-drug interactions. Our database
      gather in one document drug-drug interactions that come from different
      bibliographic sources. The setting of this database is part of the
      multidisciplinary caring of cancer patient. Drug-drug interaction is a field
      which for physicians and pharmacists should developed collaboration for patient
      care.

PMID- 17535787
TI  - [Complementary and alternative medicines taken by cancer patients].
AB  - 244 cancer patients from 2 public hospitals (one adult, one pediatric) and one
      private clinic receiving chemotherapy were asked about complementary and
      alternative medicine (CAM). Nearly 28% used one or several CAM, especially
      homeopathy (60%), special diets or dietary supplements (44%), mistletoe (40%) and
      less frequently acupuncture or other treatments. These CAM are started 4 to 5
      months after the onset of chemotherapy. The reasons for using CAM are enhance
      host defenses, better tolerance of treatment, but also for nearly 27% to treat
      cancer. All patients were treated by anticancer classical treatments and none
      thought to stop them. CAM are prescribed especially by homeopathic doctors. 30%
      of patients using CAM did not inform their oncologist of their CAM treatment. The
      same conclusions were drawn for the only 10 pediatric patients. The majority of
      all patients did not take any CAM before their cancer. In a multivariate
      analysis, female, young age (30-50 y) are correlated to CAM. All patients taking
      CAM are satisfied by the CAM treatment with good subjective results on their
      general status, fatigue and nausea-vomiting. These results are similar to other
      studies done in Europe.

PMID- 17535788
TI  - [48th World Congress of the American Society of Hematology].

PMID- 17535789
TI  - The olfactory receptor gene repertoires in secondary-adapted marine vertebrates:
      evidence for reduction of the functional proportions in cetaceans.
AB  - An olfactory receptor (OR) multigene family is responsible for the well-developed
      sense of smell possessed by terrestrial tetrapods. Mammalian OR genes had
      diverged greatly in the terrestrial environment after the fish-tetrapod split,
      indicating their importance to land habitation. In this study, we analysed OR
      genes of marine tetrapods (minke whale Balaenoptera acutorostrata, dwarf sperm
      whale Kogia sima, Dall's porpoise Phocoenoides dalli, Steller's sea lion
      Eumetopias jubatus and loggerhead sea turtle Caretta caretta) and revealed that
      the pseudogene proportions of OR gene repertoires in whales were significantly
      higher than those in their terrestrial relative cattle and also in sea lion and
      sea turtle. On the other hand, the pseudogene proportion of OR sequences in sea
      lion was not significantly higher compared with that in their terrestrial
      relative (dog). It indicates that secondary perfectly adapted marine vertebrates
      (cetaceans) have lost large amount of their OR genes, whereas secondary-semi
      adapted marine vertebrates (sea lions and sea turtles) still have maintained
      their OR genes, reflecting the importance of terrestrial environment for these
      animals.

PMID- 17535790
TI  - Bayesian inference of population expansions in domestic bovines.
AB  - The past population dynamics of four domestic and one wild species of bovine were
      estimated using Bayesian skyline plots, a coalescent Markov chain Monte Carlo
      method that does not require an assumed parametric model of demographic history.
      Four domestic species share a recent rapid population expansion not visible in
      the wild African buffalo (Syncerus caffer). The estimated timings of the
      expansions are consistent with the archaeological records of domestication.

PMID- 17535791
TI  - Male soldier caste larvae are non-aggressive in the polyembryonic wasp Copidosoma
      floridanum.
AB  - Polyembryonic wasps are the only parasitoids in which sociality has evolved.
      Theory implicates both competition and sex ratio manipulation in the evolution of
      a sterile soldier caste. However, investment in soldiers by males and females is
      predicted to differ depending upon how offspring are allocated to hosts and the
      mating system. Here, we compared male and female soldiers in the polyembryonic
      wasp Copidosoma floridanum. We found that male and female soldiers are
      morphologically identical. Unlike females, however, male soldiers were non
      aggressive towards all competitors. We discuss these results in relation to
      theory and polyembryonic wasp biology.

PMID- 17535792
TI  - Violations of transitivity under fitness maximization.
AB  - We present a novel demonstration that violations of transitive choice can result
      from decision strategies that maximize fitness. Our results depend on how the
      available options, including options not currently chosen, influence a decision
      maker's expectations about the future. In particular, they depend on how the
      presence of an option may act as an insurance against a run of bad luck in the
      future.

PMID- 17535794
TI  - Wood ants use resin to protect themselves against pathogens.
AB  - Social life is generally associated with an increased exposure to pathogens and
      parasites, due to factors such as high population density, frequent physical
      contact and the use of perennial nest sites. However, sociality also permits the
      evolution of new collective behavioural defences. Wood ants, Formica
      paralugubris, commonly bring back pieces of solidified coniferous resin to their
      nest. Many birds and a few mammals also incorporate green plant material into
      their nests. Collecting plant material rich in volatile compounds might be an
      efficient way to fight bacteria and fungi. However, no study has demonstrated
      that this behaviour has a positive effect on survival. Here, we provide the first
      experimental evidence that animals using plant compounds with antibacterial and
      antifungal properties survive better when exposed to detrimental micro-organisms.
      The presence of resin strongly improves the survival of F. paralugubris adults
      and larvae exposed to the bacteria Pseudomonas fluorescens, and the survival of
      larvae exposed to the entomopathogenic fungus Metarhizium anisopliae. These
      results show that wood ants capitalize on the chemical defences which have
      evolved in plants to collectively protect themselves against pathogens.

PMID- 17535793
TI  - Practical and theoretical advances in predicting the function of a protein by its
      phylogenetic distribution.
AB  - The gap between the amount of genome information released by genome sequencing
      projects and our knowledge about the proteins' functions is rapidly increasing.
      To fill this gap, various 'genomic-context' methods have been proposed that
      exploit sequenced genomes to predict the functions of the encoded proteins. One
      class of methods, phylogenetic profiling, predicts protein function by
      correlating the phylogenetic distribution of genes with that of other genes or
      phenotypic characteristics. The functions of a number of proteins, including ones
      of medical relevance, have thus been predicted and subsequently confirmed
      experimentally. Additionally, various approaches to measure the similarity of
      phylogenetic profiles and to account for the phylogenetic bias in the data have
      been proposed. We review the successful applications of phylogenetic profiling
      and analyse the performance of various profile similarity measures with a set of
      one microsporidial and 25 fungal genomes. In the fungi, phylogenetic profiling
      yields high-confidence predictions for the highest and only the highest scoring
      gene pairs illustrating both the power and the limitations of the approach. Both
      practical examples and theoretical considerations suggest that in order to get a
      reliable and specific picture of a protein's function, results from phylogenetic
      profiling have to be combined with other sources of evidence.

PMID- 17535795
TI  - Genetic analysis reveals promiscuity among female cheetahs.
AB  - Cheetahs (Acinonyx jubatus) have a combination of ranging patterns and social
      system that is unique in mammals, whereby male coalitions occupy small
      territories less than 10% of the home range of solitary females. This study uses
      non-invasive genetic sampling of a long-term study population of cheetah in the
      Serengeti National Park in Tanzania to infer the mating system. Individual
      cheetah genotypes at up to 13 microsatellite loci were obtained from 171 faecal
      samples. A statistical method was adapted to partition the cubs within each
      litter (n=47) into full-sibling clusters and to infer the father of each cluster
      using these loci. Our data showed a high rate of multiple paternity in the
      population; 43% of litters with more than one cub were fathered by more than one
      male. The results also demonstrated that female fidelity was low, and provided
      some evidence that females chose to mate with unrelated males within an oestrus
      cycle. The low rate of paternity assignments indicated that males living outside
      the study area contributed substantially to the reproduction of the cheetah
      population.

PMID- 17535796
TI  - Context dependence in the coevolution of plant and rhizobial mutualists.
AB  - Several mechanisms are expected to rapidly rid mutualisms of genetic variation in
      partner quality. Variation for mutualist quality, however, appears to be
      widespread. We used a model legume-rhizobium mutualism to test for evidence that
      context-dependent selection may maintain variation in partner quality. In a
      greenhouse experiment using 10 natural populations of Medicago truncatula and two
      strains of Sinorhizobium medicae, we detected significant genotype x genotype (G
      x G) interactions for plant fitness, indicating that the most beneficial
      rhizobium strain depends on the host genotype. In a second experiment using a
      subset of the plant populations used in the first experiment, we detected
      significant G x G interactions for both plant and rhizobium fitness. Moreover,
      the plant population with which rhizobium strains gained the greatest benefit
      depended on the nitrogen environment. Finally, we found that in a high nitrogen
      environment, all plant populations had lower fitness when inoculated with a 1:1
      mixture of strains than with the worse single strain alone, suggesting that
      nitrogen shifts the exchange of benefits in favour of rhizobia. Our data suggest
      that genotype, nitrogen and biotic dependency might contribute to the maintenance
      of genetic variation in mutualist quality when coupled with spatial or temporal
      heterogeneity in the environment.

PMID- 17535797
TI  - Springs and wire plants: anachronistic defences against Madagascar's extinct
      elephant birds.
AB  - The extinction of large vertebrates in the last few millennia has left a legacy
      of evolutionary anachronisms. Among these are plant structural defences that
      persist long after the extinction of the browsers. A peculiar, and controversial,
      example is a suite of traits common in divaricate (wide-angled branching) plants
      from New Zealand. Divaricate architecture has been interpreted as an adaptive
      response to cold climates or an anachronistic defence against the extinct moas.
      Madagascar, a larger tropical island, also had a fauna of large flightless birds,
      the elephant birds. If these extinct ratites selected for similar plant defences,
      we expected to find convergent features between New Zealand and Malagasy plants,
      despite their very different climates. We searched the southern thickets of
      Madagascar for plants with putative anti-ratite defences and scored candidate
      species for a number of traits common to many New Zealand divaricates. We found
      many Malagasy species in 25 families and 36 genera shared the same suite of
      traits, the 'wire plant' syndrome, as divaricates in New Zealand that resist
      ratite browsing. Neither ecologically, nor phylogenetically, matched species from
      South Africa shared these traits. Malagasy wire plants differ from many New
      Zealand divaricates in lacking the distinctive concentration of leaves in the
      interior of shrubs. We suggest that New Zealand divaricates have a unique amalgam
      of traits that acted as defences and also confer tolerance to cold. We conclude
      that many woody species in the thickets of southern Madagascar share, with New
      Zealand, anachronistic structural defences against large extinct bird browsers.

PMID- 17535798
TI  - Grazing protozoa and the evolution of the Escherichia coli O157:H7 Shiga toxin
      encoding prophage.
AB  - Humans play little role in the epidemiology of Escherichia coli O157:H7, a
      commensal bacterium of cattle. Why then does E. coli O157:H7 code for virulence
      determinants, like the Shiga toxins (Stxs), responsible for the morbidity and
      mortality of colonized humans? One possibility is that the virulence of these
      bacteria to humans is coincidental and these virulence factors evolved for and
      are maintained for other roles they play in the ecology of these bacteria. Here,
      we test the hypothesis that the carriage of the Stx-encoding prophage of E. coli
      O157:H7 increases the rate of survival of E. coli in the presence of grazing
      protozoa, Tetrahymena pyriformis. In the presence but not the absence of
      Tetrahymena, the carriage of the Stx-encoding prophage considerably augments the
      fitness of E. coli K-12 as well as clinical isolates of E. coli O157 by
      increasing the rate of survival of the bacteria in the food vacuoles of these
      ciliates. Grazing protozoa in the environment or natural host are likely to play
      a significant role in the ecology and maintenance of the Stx-encoding prophage of
      E. coli O157:H7 and may well contribute to the evolution of the virulence of
      these bacteria to colonize humans.

PMID- 17535799
TI  - A conserved mechanism for steroid receptor translocation to the plasma membrane.
AB  - Multiple steroid receptors (SR) have been proposed to localize to the plasma
      membrane. Some structural elements for membrane translocation of the estrogen
      receptor alpha (ER alpha) have been described, but the mechanisms relevant to
      other steroid receptors are entirely unknown. Here, we identify a highly
      conserved 9 amino acid motif in the ligand binding domains (E domains) of
      human/mouse ER alpha and ER beta, progesterone receptors A and B, and the
      androgen receptor. Mutation of the phenylalanine or tyrosine at position-2,
      cysteine at position 0, and hydrophobic isoleucine/leucine or leucine/leucine
      combinations at positions +5/6, relative to cysteine, significantly reduced
      membrane localization, MAP and PI 3-kinase activation, thymidine incorporation
      into DNA, and cell viability, stimulated by specific SR ligands. The localization
      sequence mediated palmitoylation of each SR, which facilitated caveolin-1
      association, subsequent membrane localization, and steroid signaling.
      Palmitoylation within the E domain is therefore a crucial modification for
      membrane translocation and function of classical sex steroid receptors.

PMID- 17535800
TI  - Regulation of the Pro-apoptotic scaffolding protein POSH by Akt.
AB  - POSH (Plenty of SH3 domains) binds to activated Rac and promotes apoptosis by
      acting as a scaffold to assemble a signal transduction pathway leading from Rac
      to JNK activation. Overexpression of POSH induces apoptosis in a variety of cell
      types, but apoptosis can be prevented by co-expressing the pro-survival protein
      kinase Akt. We report here that POSH is a direct substrate for phosphorylation by
      Akt in vivo and in vitro, and we identify a major site of Akt phosphorylation as
      serine 304 of POSH, which lies within the Rac-binding domain. We further show
      that phosphorylation of POSH results in a decreased ability to bind activated
      Rac, as does phosphomimetic S304D and S304E mutation of POSH. S304D mutant POSH
      also shows a strongly reduced ability to induce apoptosis. These findings
      identify a novel mechanism by which Akt promotes cell survival.

PMID- 17535801
TI  - Regulation of ERGIC-53 gene transcription in response to endoplasmic reticulum
      stress.
AB  - Accumulation of unfolded proteins within the endoplasmic reticulum (ER) activates
      the unfolded protein response, also known as the ER stress response. We
      previously demonstrated that ER stress induces transcription of the ER Golgi
      intermediate compartment protein ERGIC-53. To investigate the molecular events
      that regulate unfolded protein response-mediated induction of the gene, we have
      analyzed the transcriptional regulation of ERGIC-53. We found that the ERGIC-53
      promoter contains a single cis-acting element that mediates induction of the gene
      by thapsigargin and other ER stress-causing agents. This ER stress response
      element proved to retain a novel structure and to be highly conserved in
      mammalian ERGIC-53 genes. The ER stress response element identified contains a 5'
      end CCAAT sequence that constitutively binds NFY/CBF and, 9 nucleotides away, a
      3'-end region (5'-CCCTGTTGGCCATC-3') that is equally important for ER stress
      mediated induction of the gene. This sequence is the binding site for endogenous
      YY1 at the 5'-CCCTGTTGG-3' part and for undefined factors at the CCATC 3'-end.
      ATF6 alpha-YY1, but not XBP1, interacted with the ERGIC-53 regulatory region and
      activated ERGIC-53 ER stress response element-dependent transcription. A
      molecular model for the transcriptional regulation of the ERGIC-53 gene is
      proposed.

PMID- 17535802
TI  - Inhibition of the activation of multiple serine proteases with a cathepsin C
      inhibitor requires sustained exposure to prevent pro-enzyme processing.
AB  - Cathepsin C is a cysteine protease required for the activation of several pro
      inflammatory serine proteases and, as such, is of interest as a therapeutic
      target. In cathepsin C-deficient mice and humans, the N-terminal processing and
      activation of neutrophil elastase, cathepsin G, and proteinase-3 is abolished and
      is accompanied by a reduction of protein levels. Pharmacologically, the
      consequence of cathepsin C inhibition on the activation of these serine proteases
      has not been described, due to the lack of stable and non-toxic inhibitors and
      the absence of appropriate experimental cell systems. Using novel reversible
      peptide nitrile inhibitors of cathepsin C, and cell-based assays with U937 and
      EcoM-G cells, we determined the effects of pharmacological inhibition of
      cathepsin C on serine protease activity. We show that indirect and complete
      inhibition of neutrophil elastase, cathepsin G, and proteinase-3 is achievable in
      intact cells with selective and non-cytotoxic cathepsin C inhibitors, at
      concentrations approximately 10-fold higher than those required to inhibit
      purified cathepsin C. The concentration of inhibitor needed to block processing
      of these three serine proteases was similar, regardless of the cell system used.
      Importantly, cathepsin C inhibition must be sustained to maintain serine protease
      inhibition, because removal of the reversible inhibitors resulted in the
      activation of pro-enzymes in intact cells. These findings demonstrate that near
      complete inhibition of multiple serine proteases can be achieved with cathepsin C
      inhibitors and that cathepsin C inhibition represents a viable but challenging
      approach for the treatment of neutrophil-based inflammatory diseases.

PMID- 17535803
TI  - Specific recognition of the -10 promoter element by the free RNA polymerase sigma
      subunit.
AB  - Bacterial RNA polymerase holoenzyme relies on its sigma subunit for promoter
      recognition and opening. In the holoenzyme, regions 2 and 4 of the sigma subunit
      are positioned at an optimal distance to allow specific recognition of the -10
      and -35 promoter elements, respectively. In free sigma, the promoter binding
      regions are positioned closer to each other and are masked for interactions with
      the promoter, with sigma region 1 playing a role in the masking. To analyze the
      DNA-binding properties of the free sigma, we selected single-stranded DNA
      aptamers that are specific to primary sigma subunits from several bacterial
      species, including Escherichia coli and Thermus aquaticus. The aptamers share a
      consensus motif, TGTAGAAT, that is similar to the extended -10 promoter. We
      demonstrate that recognition of this motif by sigma region 2 occurs without major
      structural rearrangements of sigma observed upon the holoenzyme formation and is
      not inhibited by sigma regions 1 and 4. Thus, the complex process of the -10
      element recognition by RNA polymerase holoenzyme can be reduced to a simple
      system consisting of an isolated sigma subunit and a short aptamer
      oligonucleotide.

PMID- 17535804
TI  - Caveolin-associated accumulation of globotriaosylceramide in the vascular
      endothelium of alpha-galactosidase A null mice.
AB  - Cardiovascular complications, including stroke and myocardial infarction, result
      in premature mortality in patients with Fabry disease, an X-linked deficiency of
      alpha-galactosidase A (alpha-Gal A). The enzymatic defect results in the
      deposition of globotriaosylceramide (Gb3) in the vascular endothelium. To better
      understand the underlying pathogenesis of Fabry disease, the caveolar lipid
      content of primary cultured mouse aortic endothelial cells isolated from alpha
      Gal A null mice was measured. Lipid mass analysis revealed that the excessive Gb3
      in cultured alpha-Gal A-deficient mouse aortic endothelial cells accumulated in
      endothelial plasma membrane caveolar fractions. The levels of glucosylceramide
      and lactosylceramide increased in parallel with Gb3 levels in an age-dependent
      manner, whereas globotetraosylceramide (Gb4) levels reached maximal levels by 6
      months of age and then rapidly decreased at older ages. The levels of cholesterol
      enriched in caveolar membranes declined in parallel with the progressive
      deposition of Gb3. Depleting Gb3 with recombinant human alpha-Gal A protein or d
      threo-ethylenedioxyphenyl-P4, an inhibitor of glucosylceramide synthase, restored
      cholesterol in cultured alpha-Gal A-deficient mouse aortic endothelial cell
      caveolae. By contrast, recombinant human alpha-Gal A was less effective in
      normalizing the cholesterol content. These results demonstrate the caveolar
      accumulation of glycosphingolipids in an in vitro model of a lysosomal storage
      disease and raise the possibility that dynamic changes in the composition of
      plasma membrane lipid microdomains may mediate the endothelial dysfunction seen
      in Fabry disease.

PMID- 17535805
TI  - Critical role of the heme axial ligand, Met95, in locking catalysis of the
      phosphodiesterase from Escherichia coli (Ec DOS) toward Cyclic diGMP.
AB  - Heme-regulated phosphodiesterase from Escherichia coli (Ec DOS) is a gas-sensor
      enzyme that hydrolyzes cyclic dinucleotide-GMP, and it is activated by O(2) or CO
      binding to the Fe(II) heme. In contrast to other well known heme-regulated gas
      sensor enzymes or proteins, Ec DOS is not specific for a single gas ligand.
      Because Arg(97) in the heme distal side in Ec DOS interacts with the O(2)
      molecule and Met(95) serves as the axial ligand on the distal side of the Fe(II)
      heme-bound PAS domain of Ec DOS, we explored the effect of mutating these
      residues on the activity and gas specificity of Ec DOS. We found that R97A, R97I,
      and R97E mutations do not significantly affect regulation of the
      phosphodiesterase activities of the Fe(II)-CO and Fe(II)-NO complexes. The
      phosphodiesterase activities of the Fe(II)-O(2) complexes of the mutants could
      not be detected due to rapid autoxidation and/or low affinity for O(2). In
      contrast, the activities even of the gas-free M95A and M95L mutants were similar
      to that of the gas-activated wild-type enzyme. Interestingly, the activity of the
      M95H mutant was partially activated by O(2), CO, and NO. Spectroscopic analysis
      indicated that the Fe(II) heme is in the 5-coordinated high-spin state in the
      M95A and M95L mutants but that in the M95H mutant, like wild-type Ec DOS, it is
      in the 6-coordinated low-spin state. These results suggest that Met(95)
      coordination to the Fe(II) heme is critical for locking the system and that
      global structural changes around Met(95) caused by the binding of the external
      ligands or mutations at Met(95) releases the catalytic lock and activates
      catalysis.

PMID- 17535806
TI  - TLR-4 and sustained calcium agonists synergistically produce eicosanoids
      independent of protein synthesis in RAW264.7 cells.
AB  - Arachidonic acid is released by phospholipase A(2) and converted into hundreds of
      distinct bioactive mediators by a variety of cyclooxygenases (COX), lipoxygenases
      (LO), and cytochrome P450s. Because of the size and diversity of the eicosanoid
      class of signaling molecules produced, a thorough and systematic investigation of
      these biological processes requires the simultaneous quantitation of a large
      number of eicosanoids in a single analysis. We have developed a robust liquid
      chromatography/tandem mass spectrometry method that can identify and quantitate
      over 60 different eicosanoids in a single analysis, and we applied it to agonist
      stimulated RAW264.7 murine macrophages. Fifteen different eicosanoids produced
      through COX and 5-LO were detected either intracellularly or in the media
      following stimulation with 16 different agonists of Toll-like receptors (TLR), G
      protein-coupled receptors, and purinergic receptors. No significant differences
      in the COX metabolite profiles were detected using the different agonists;
      however, we determined that only agonists creating a sustained Ca(2+) influx were
      capable of activating the 5-LO pathway in these cells. Synergy between Ca(2+) and
      TLR pathways was detected and discovered to be independent of NF-kappaB-induced
      protein synthesis. This demonstrates that TLR induction of protein synthesis and
      priming for enhanced phospholipase A(2)-mediated eicosanoid production work
      through two distinct pathways.

PMID- 17535807
TI  - Regulation of transcript elongation through cooperative and ordered recruitment
      of cofactors.
AB  - We studied the regulation of murine CD80, a gene whose basal transcriptional
      status was characterized by the presence of a stalled RNA polymerase II complex
      on the promoter-proximal region. Stimulus-induced activation of productive
      elongation involved a complex interplay of regulated events that included a
      synergy between ordered cofactor recruitment. This cascade of recruitments was
      initiated through the engagement of transcription factor NF-kappaB, leading to
      the temporal association of histone acetyltransferases and the consequent
      selective acetylation of a transcription start site downstream nucleosome. This
      in turn culminated into the nucleosomal association of Brd4-associated P-TEFb, a
      protein complex containing kinase specific for serine 2 of Rbp 1, the largest
      subunit of the carboxyl-terminal domain of RNA polymerase II. The consequent
      phosphorylation of serine 2 residues in CTD by CDK9 in the P-TEFb complex then
      facilitated escape of polymerase II into the productive elongation phase. Thus,
      the cooperative mechanisms that integrate between independent pathways
      characterize regulation of the elongation step of transcription, thereby
      providing another level at which specificity of gene regulation can be achieved.

PMID- 17535808
TI  - Post-translational regulation of human indoleamine 2,3-dioxygenase activity by
      nitric oxide.
AB  - The heme protein indoleamine 2,3-dioxygenase (IDO) is induced by the
      proinflammatory cytokine interferon-gamma (IFNgamma) and plays an important role
      in the immune response by catalyzing the oxidative degradation of L-tryptophan
      (Trp) that contributes to immune suppression and tolerance. Here we examined the
      mechanism by which nitric oxide (NO) inhibits human IDO activity. Exposure of
      IFNgamma-stimulated human monocyte-derived macrophages (MDM) to NO donors had no
      material impact on IDO mRNA or protein expression, yet exposure of MDM or
      transfected COS-7 cells expressing active human IDO to NO donors resulted in
      reversible inhibition of IDO activity. NO also inhibited the activity of purified
      recombinant human IDO (rhIDO) in a reversible manner and this correlated with NO
      binding to the heme of rhIDO. Optical absorption and resonance Raman spectroscopy
      identified NO-inactivated rhIDO as a ferrous iron (Fe(II))-NO-Trp adduct. Stopped
      flow kinetic studies revealed that NO reacted most rapidly with Fe(II) rhIDO in
      the presence of Trp. These findings demonstrate that NO inhibits rhIDO activity
      reversibly by binding to the active site heme to trap the enzyme as an inactive
      nitrosyl-Fe(II) enzyme adduct with Trp bound and O2 displaced. Reversible
      inhibition by NO may represent an important mechanism in controlling the immune
      regulatory actions of IDO.

PMID- 17535809
TI  - Selective inhibition of Cav3.3 T-type calcium channels by Galphaq/11-coupled
      muscarinic acetylcholine receptors.
AB  - T-type calcium channels play critical roles in controlling neuronal excitability,
      including the generation of complex spiking patterns and the modulation of
      synaptic plasticity, although the mechanisms and extent to which T-type Ca(2+)
      channels are modulated by G-protein-coupled receptors (GPCRs) remain largely
      unexplored. To examine specific interactions between T-type Ca(2+) channel
      subtypes and muscarinic acetylcholine receptors (mAChRS), the Cav3.1 (alpha(1G)),
      Cav3.2 (alpha(1H)), and Cav3.3 (alpha) T-type Ca(2+)(1I)channels were co
      expressed with the M1 Galpha(q/11)-coupled mAChR. Perforated patch recordings
      demonstrate that activation of M1 receptors has a strong inhibitory effect on
      Cav3.3 T-type Ca(2+) currents but either no effect or a moderate stimulating
      effect on Cav3.1 and Cav3.2 peak current amplitudes. This differential modulation
      was observed for both rat and human T-type Ca(2+) channel variants. The
      inhibition of Cav3.3 channels by M1 receptors is reversible, use-independent, and
      associated with a concomitant increase in inactivation kinetics. Loss-of-function
      experiments with genetically encoded antagonists of Galpha and Gbetagamma
      proteins and gain-of-function experiments with genetically encoded Galpha
      subtypes indicate that M1 receptor-mediated inhibition of Cav3.3 occurs through
      Galpha(q/11). This is supported by experiments showing that activation of the M3
      and M5 Galpha(q/11)-coupled mAChRs also causes inhibition of Cav3.3 currents,
      although Galpha(i)-coupled mAChRs (M2 and M4) have no effect. Examining Cav3.1
      Cav3.3 chimeric channels demonstrates that two distinct regions of the Cav3.3
      channel are necessary and sufficient for complete M1 receptor-mediated channel
      inhibition and represent novel sites not previously implicated in T-type channel
      modulation.

PMID- 17535810
TI  - Functional similarity between the chloroplast translocon component, Tic40, and
      the human co-chaperone, Hsp70-interacting protein (Hip).
AB  - Tic40 is a component of the protein import apparatus of the inner envelope of
      chloroplasts, but its role in the import mechanism has not been clearly defined.
      The C terminus of Tic40 shares weak similarity with the C-terminal Sti1 domains
      of the mammalian Hsp70-interacting protein (Hip) and Hsp70/Hsp90-organizing
      protein (Hop) co-chaperones. Additionally, Tic40 may possess a tetratricopeptide
      repeat (TPR) protein-protein interaction domain, another characteristic feature
      of Hip/Hop co-chaperones. To investigate the functional importance of different
      parts of the Tic40 protein and to determine whether the homology between Tic40
      and co-chaperones is functionally significant, different Tic40 deletion and
      Tic40:Hip fusion constructs were generated and assessed for complementation
      activity in the Arabidopsis Tic40 knock-out mutant, tic40. Interestingly, all
      Tic40 deletion constructs failed to complement tic40, indicating that each part
      removed is essential for Tic40 function; these included a construct lacking the
      Sti1-like domain (DeltaSti1), a second lacking a central region, including the
      putative TPR domain (DeltaTPR), and a third lacking the predicted transmembrane
      anchor region. Moreover, the DeltaSti1 and DeltaTPR constructs caused strong
      dominant-negative, albino phenotypes in tic40 transformants, indicating that the
      truncated Tic40 proteins interfere with the residual chloroplast protein import
      that occurs in tic40 plants. Remarkably, the Tic40:Hip fusion constructs showed
      that the Sti1 domain of human Hip is functionally equivalent to the Sti1-like
      region of Tic40, strongly suggesting a co-chaperone role for the Tic40 protein.
      Supporting this notion, yeast two-hybrid and bimolecular fluorescence
      complementation assays demonstrated the in vivo interaction of Tic40 with Tic110,
      a protein believed to recruit stromal chaperones to protein import sites.

PMID- 17535811
TI  - NFBD1/MDC1 associates with p53 and regulates its function at the crossroad
      between cell survival and death in response to DNA damage.
AB  - NFBD1/MDC1, which belongs to the BRCT superfamily, has an anti-apoptotic activity
      and contributes to the early cellular responses to DNA damage. Here we found that
      NFBD1 protects cells from apoptotic cell death by inhibiting phosphorylation of
      p53 at Ser-15 under steady state as well as early phase of DNA damage, thereby
      blocking its transcriptional and pro-apoptotic activities. During late phase of
      DNA damage, a remarkable reduction of NFBD1 was observed in dying but not in
      surviving A549 cells bearing wild-type p53. Small interference RNA-mediated
      knockdown of the endogenous NFBD1 resulted in an increase in sensitivity to
      adriamycin in A549 cells but not in p53-deficient H1299 cells.
      Immunoprecipitation and luciferase reporter analyses demonstrated that NFBD1
      binds to the NH(2)-terminal region of p53 and strongly inhibits its
      transcriptional activity. Additionally, BRCT domains, which can interact with
      p53, reduced the adriamycin-induced phosphorylation levels of p53 at Ser-15 and
      also suppressed the transcriptional activity of p53. Thus, our present findings
      strongly suggest that NFBD1 plays an important role in the decision of cell
      survival and death after DNA damage through the regulation of p53.

PMID- 17535812
TI  - Grb10 and active Raf-1 kinase promote Bad-dependent cell survival.
AB  - The proapoptotic protein Bad is a key player in cell survival decisions, and is
      regulated post-translationally by several signaling networks. We expressed Bad in
      mouse embryonic fibroblasts to sensitize them to apoptosis, and tested cell lines
      derived from knock-out mice to establish the significance of the interaction
      between the adaptor protein Grb10 and the Raf-1 protein kinase in anti-apoptotic
      signaling pathways targeting Bad. When compared with wild-type cells, both Grb10
      and Raf-1-deficient cells exhibit greatly enhanced sensitivity to apoptosis in
      response to Bad expression. Structure-function analysis demonstrates that, in
      this cellular model, the SH2, proline-rich, and pleckstrin homology domains of
      Grb10, as well as its Akt phosphorylation site and consequent binding by 14-3-3,
      are all necessary for its anti-apoptotic functions. As for Raf-1, its kinase
      activity, its ability to be phosphorylated by Src on Tyr-340/341 and the binding
      of its Ras-associated domain to the Grb10 SH2 domain are all necessary to promote
      cell survival. Silencing the expression of either Grb10 or Raf-1 by small
      interfering RNAs as well as mutagenesis of specific serine residues on Bad,
      coupled with signaling inhibitor studies, all indicate that Raf-1 and Grb10 are
      required for the ability of both the phosphatidylinositol 3-kinase/Akt and MAP
      kinase pathways to modulate the phosphorylation and inactivation of Bad. Because
      total Raf-1, ERK, and Akt kinase activities are not impaired in the absence of
      Grb10, we propose that this adapter protein creates a subpopulation of Raf-1 with
      specific anti-apoptotic activity.

PMID- 17535813
TI  - Differential repression by freud-1/CC2D1A at a polymorphic site in the dopamine
      D2 receptor gene.
AB  - Freud-1/CC2D1A is a transcriptional repressor of the serotonin-1A receptor gene
      and was recently genetically linked to non-syndromic mental retardation. To
      identify new Freud-1 gene targets, data base mining for Freud-1 recognition
      sequences was done. A highly homologous intronic element (D2-DRE) was identified
      in the human dopamine-D2 receptor (DRD2) gene, and the role of Freud-1 in
      regulating the gene at this site was assessed. Recombinant Freud-1 bound
      specifically to the D2-DRE, and a major protein-D2-DRE complex was identified in
      nuclear extracts that was supershifted using Freud-1-specific antibodies.
      Endogenous Freud-1 binding to the D2-DRE in cells was detected using chromatin
      immunoprecipitation. The D2-DRE conferred strong repressor activity in
      transcriptional reporter assays that was dependent on the Freud-1 recognition
      sequence. In three different human cell lines, the level of Freud-1 protein was
      inversely related to DRD2 expression. Knockdown of endogenous Freud-1 using small
      interfering RNA resulted in an up-regulation of DRD2 RNA and binding sites,
      demonstrating a crucial role for Freud-1 in DRD2 regulation. A previously
      uncharacterized single nucleotide A/G polymorphism (rs2734836) was located
      adjacent to the D2-DRE and conferred allele-specific Freud-1 binding and
      repression, with the major G-allele having reduced activity. These studies
      demonstrate a key role for Freud-1 to regulate DRD2 expression and provide the
      first mechanistic insights into its transcriptional regulation. Allele-specific
      regulation of DRD2 expression by Freud-1 may possibly associate with psychiatric
      disorders or mental retardation.

PMID- 17535814
TI  - Human NUF2 interacts with centromere-associated protein E and is essential for a
      stable spindle microtubule-kinetochore attachment.
AB  - Chromosome segregation in mitosis is orchestrated by dynamic interaction between
      spindle microtubules and the kinetochore, a multiprotein complex assembled onto
      centromeric DNA of the chromosome. Here, we show that Homo sapiens (Hs) NUF2 is
      required for stable kinetochore localization of centromere-associated protein E
      (CENP-E) in HeLa cells. HsNUF2 specifies the kinetochore association of CENP-E by
      interacting with its C-terminal domain. The region of HsNUF2 binding to CENP-E
      was mapped to its C-terminal domain by glutathione S-transferase pulldown and
      yeast two-hybrid assays. Suppression of synthesis of HsNUF2 by small interfering
      RNA abrogated the localization of CENP-E to the kinetochore, demonstrating the
      requirement of HsNUF2 for CENP-E kinetochore localization. In addition, depletion
      of HsNUF2 caused aberrant chromosome segregation. These HsNUF2-suppressed cells
      displayed reduced tension at kinetochores of bi-orientated chromosomes. Double
      knockdown of CENP-E and HsNUF2 further abolished the tension at the kinetochores.
      Our results indicate that HsNUF2 and CENP-E are required for organization of
      stable microtubule-kinetochore attachment that is essential for faithful
      chromosome segregation in mitosis.

PMID- 17535815
TI  - Acetylated histone tail peptides induce structural rearrangements in the RSC
      chromatin remodeling complex.
AB  - Post-translational acetylation of histone tails is often required for the
      recruitment of ATP-dependent chromatin remodelers, which in turn mobilize
      nucleosomes on the chromatin fiber. Here we show that the lower lobe of the ATP
      dependent chromatin remodeler RSC exists in a dynamic equilibrium and can be
      found extended away or retracted against the tripartite upper lobe of the
      complex. Extension of the lower lobe increases the size of a central cavity that
      has been proposed to be the nucleosome binding site. We show that the presence of
      acetylated histone 3 N-terminal tail peptides stabilizes the lower lobe of RSC in
      the retracted state, suggesting that domains recognizing the acetylated histone
      tails reside at the interface between the two lobes. Based on three-dimensional
      reconstructions, we propose a model for the interaction of RSC with acetylated
      nucleosomes.

PMID- 17535816
TI  - Identification of a soluble diacylglycerol kinase required for lipoteichoic acid
      production in Bacillus subtilis.
AB  - Diacylglycerol kinases (DagKs) are key enzymes in lipid metabolism that function
      to reintroduce diacylglycerol formed from the hydrolysis of phospholipids into
      the biosynthetic pathway. Bacillus subtilis is a prototypical Gram-positive
      bacterium with a lipoteichoic acid structure containing repeating units of sn
      glycerol-1-P groups derived from phosphatidylglycerol head groups. The B.
      subtilis homolog of the prokaryotic DagK gene family (dgkA; Pfam01219) was not a
      DagK but rather was an undecaprenol kinase. The three members of the soluble DagK
      protein family (Pfam00781) in B. subtilis were tested by complementation of an E.
      coli dgkA mutant, and only the essential yerQ gene possessed DagK activity. This
      gene was dubbed dgkB, and the soluble protein product was purified, and its DagK
      activity was verified in vitro. Conditional inactivation of dgkB led to the
      accumulation of diacylglycerol and the cessation of lipoteichoic acid formation
      in B. subtilis. This study identifies a soluble protein encoded by the dgkB
      (yerQ) gene as an essential kinase in the diacylglycerol cycle that drives
      lipoteichoic acid production.

PMID- 17535817
TI  - Comprehensive Feeding Practices Questionnaire: validation of a new measure of
      parental feeding practices.
AB  - OBJECTIVE: Measures of parents' feeding practices have focused primarily on
      parental control of feeding and have not sufficiently measured other potentially
      important practices. The current study validates a new measure of feeding
      practices, the Comprehensive Feeding Practices Questionnaire (CFPQ). METHOD: The
      first study validated a 9-factor feeding practice scale for mothers and fathers.
      In the second study, open-ended questions solicited feeding practices from
      parents to develop a more comprehensive measure of parental feeding. The third
      study validated an expanded 12-factor feeding practices measure with mothers of
      children from 2 to 8 years of age. RESULTS: The CFPQ appears to be an adequate
      tool for measuring the feeding practices of parents of young children.
      CONCLUSIONS: Researchers, clinicians, and health educators might use this measure
      to better understand how parents feed their children, the factors that contribute
      to these practices, and the implications of these practices on children's eating
      behaviors.

PMID- 17535818
TI  - Measuring outcomes in attention-deficit/hyperactivity disorder.

PMID- 17535819
TI  - Characterization of stress-responsive CIPK genes in rice for stress tolerance
      improvement.
AB  - Plants respond to adverse environments by initiating a series of signaling
      processes that often involves diverse protein kinases, including calcineurin B
      like protein-interacting protein kinases (CIPKs). In this study, putative CIPK
      genes (OsCIPK01-OsCIPK30) in the rice (Oryza sativa) genome were surveyed for
      their transcriptional responses to various abiotic stresses. The results showed
      that 20 OsCIPK genes were differentially induced by at least one of the stresses,
      including drought, salinity, cold, polyethylene glycol, and abscisic acid
      treatment. Most of the genes induced by drought or salt stress were also induced
      by abscisic acid treatment but not by cold. A few CIPK genes containing none of
      the reported stress-responsive cis-elements in their promoter regions were also
      induced by multiple stresses. To prove that some of these stress-responsive
      OsCIPK genes are potentially useful for stress-tolerance improvement, three CIPK
      genes (OsCIPK03, OsCIPK12, and OsCIPK15) were overexpressed in japonica rice
      'Zhonghua 11'. Transgenic plants overexpressing the transgenes OsCIPK03,
      OsCIPK12, and OsCIPK15 showed significantly improved tolerance to cold, drought,
      and salt stress, respectively. Under cold and drought stresses, OsCIPK03- and
      OsCIPK12-overexpressing transgenic plants accumulated significantly higher
      contents of proline and soluble sugars than the wild type. Putative proline
      synthetase and transporter genes had significantly higher expression level in the
      transgenic plants than in the wild type. The differentially induced expression of
      OsCIPK genes by different stresses and the examples of improved stress tolerance
      of the OsCIPK transgenic rice suggest that rice CIPK genes have diverse roles in
      different stress responses and some of them may possess potential usefulness in
      stress-tolerance improvement of rice.

PMID- 17535820
TI  - The nuclear pore protein AtTPR is required for RNA homeostasis, flowering time,
      and auxin signaling.
AB  - Nuclear pore complexes (NPCs) mediate the transport of RNA and other cargo
      between the nucleus and the cytoplasm. In vertebrates, the NPC protein
      TRANSLOCATED PROMOTER REGION (TPR) is associated with the inner filaments of the
      nuclear basket and is thought to serve as a scaffold for the assembly of
      transport machinery. In a screen for mutants that suppress the expression of the
      floral inhibitor FLOWERING LOCUS C, we identified lesions in the Arabidopsis
      (Arabidopsis thaliana) homolog of TPR (AtTPR). attpr mutants exhibit early
      flowering and other pleiotropic phenotypes. A possible explanation for these
      developmental defects is that attpr mutants exhibit an approximately 8-fold
      increase in nuclear polyA RNA. Thus AtTPR is required for the efficient export of
      RNA from the nucleus. Microarray analysis shows that, in wild type, transcript
      abundance in the nuclear and total RNA pools are highly correlated; whereas, in
      attpr mutants, a significantly larger fraction of transcripts is enriched in
      either the nuclear or total pool. Thus AtTPR is required for homeostasis between
      nuclear and cytoplasmic RNA. We also show that the effects of AtTPR on small RNA
      abundance and auxin signaling are similar to that of two other NPC-associated
      proteins, HASTY (HST) and SUPPRESSOR OF AUXIN RESISTANCE3 (SAR3). This suggests
      that AtTPR, HST, and SAR3 may play related roles in the function of the nuclear
      pore.

PMID- 17535821
TI  - A chlorophyll-deficient rice mutant with impaired chlorophyllide esterification
      in chlorophyll biosynthesis.
AB  - Chlorophyll (Chl) synthase catalyzes esterification of chlorophyllide to complete
      the last step of Chl biosynthesis. Although the Chl synthases and the
      corresponding genes from various organisms have been well characterized, Chl
      synthase mutants have not yet been reported in higher plants. In this study, a
      rice (Oryza Sativa) Chl-deficient mutant, yellow-green leaf1 (ygl1), was
      isolated, which showed yellow-green leaves in young plants with decreased Chl
      synthesis, increased level of tetrapyrrole intermediates, and delayed chloroplast
      development. Genetic analysis demonstrated that the phenotype of ygl1 was caused
      by a recessive mutation in a nuclear gene. The ygl1 locus was mapped to
      chromosome 5 and isolated by map-based cloning. Sequence analysis revealed that
      it encodes the Chl synthase and its identity was verified by transgenic
      complementation. A missense mutation was found in a highly conserved residue of
      YGL1 in the ygl1 mutant, resulting in reduction of the enzymatic activity. YGL1
      is constitutively expressed in all tissues, and its expression is not
      significantly affected in the ygl1 mutant. Interestingly, the mRNA expression of
      the cab1R gene encoding the Chl a/b-binding protein was severely suppressed in
      the ygl1 mutant. Moreover, the expression of some nuclear genes associated with
      Chl biosynthesis or chloroplast development was also affected in ygl1 seedlings.
      These results indicate that the expression of nuclear genes encoding various
      chloroplast proteins might be feedback regulated by the level of Chl or Chl
      precursors.

PMID- 17535822
TI  - Ethylene insensitivity results in down-regulation of rubisco expression and
      photosynthetic capacity in tobacco.
AB  - Little is known about the effect of hormones on the photosynthetic process.
      Therefore, we studied Rubisco content and expression along with gas exchange
      parameters in transgenic tobacco (Nicotiana tabacum) plants that are not able to
      sense ethylene. We also tested for a possible interaction between ethylene
      insensitivity, abscisic acid (ABA), and sugar feedback on photosynthesis. We
      measured Rubisco content in seedlings grown in agar with or without added sugar
      and fluridone, and Rubisco expression in hydroponically grown vegetative plants
      grown at low and high CO(2). Furthermore, we analyzed gas exchange and the
      photosynthetic machinery of transformants and wild-type plants grown under
      standard conditions. In the presence of exogenous glucose (Glc), agar-grown
      seedlings of the ethylene-insensitive genotype had lower amounts of Rubisco per
      unit leaf area than the wild type. No differences in Rubisco content were found
      between ethylene-insensitive and wild-type seedlings treated with fluridone,
      suggesting that inhibition of ABA production nullified the effect of Glc
      application. When larger, vegetative plants were grown at different atmospheric
      CO(2) concentrations, a negative correlation was found between Glc concentration
      in the leaves and Rubisco gene expression, with stronger repression by high Glc
      concentrations in ethylene-insensitive plants. Ethylene insensitivity resulted in
      plants with comparable fractions of nitrogen invested in light harvesting, but
      lower amounts in electron transport and Rubisco. Consequently, photosynthetic
      capacity of the insensitive genotype was clearly lower compared with the wild
      type. We conclude that the inability to perceive ethylene results in increased
      sensitivity to Glc, which may be mediated by a higher ABA concentration. This
      increased sensitivity to endogenous Glc has negative consequences for Rubisco
      content and photosynthetic capacity of these plants.

PMID- 17535823
TI  - Evolution of flavone synthase I from parsley flavanone 3beta-hydroxylase by site
      directed mutagenesis.
AB  - Flavanone 3beta-hydroxylase (FHT) and flavone synthase I (FNS I) are 2
      oxoglutarate-dependent dioxygenases with 80% sequence identity, which catalyze
      distinct reactions in flavonoid biosynthesis. However, FNS I has been reported
      exclusively from a few Apiaceae species, whereas FHTs are more abundant. Domain
      swapping experiments joining the N terminus of parsley (Petroselinum crispum) FHT
      with the C terminus of parsley FNS I and vice versa revealed that the C-terminal
      portion is not essential for FNS I activity. Sequence alignments identified 26
      amino acid substitutions conserved in FHT versus FNS I genes. Homology modeling,
      based on the related anthocyanidin synthase structure, assigned seven of these
      amino acids (FHT/FNS I, M106T, I115T, V116I, I131F, D195E, V200I, L215V, and
      K216R) to the active site. Accordingly, FHT was modified by site-directed
      mutagenesis, creating mutants encoding from one to seven substitutions, which
      were expressed in yeast (Saccharomyces cerevisiae) for FNS I and FHT assays. The
      exchange I131F in combination with either M106T and D195E or L215V and K216R
      replacements was sufficient to confer some FNS I side activity. Introduction of
      all seven FNS I substitutions into the FHT sequence, however, caused a nearly
      complete change in enzyme activity from FHT to FNS I. Both FHT and FNS I were
      proposed to initially withdraw the beta-face-configured hydrogen from carbon-3 of
      the naringenin substrate. Our results suggest that the 7-fold substitution
      affects the orientation of the substrate in the active-site pocket such that this
      is followed by syn-elimination of hydrogen from carbon-2 (FNS I reaction) rather
      than the rebound hydroxylation of carbon-3 (FHT reaction).

PMID- 17535824
TI  - Light-dependent regulation of cell division in Ostreococcus: evidence for a major
      transcriptional input.
AB  - Cell division often occurs at specific times of the day in animal and
      photosynthetic organisms. Studies in unicellular photosynthetic algae, such as
      Chlamydomonas or Euglena, have shown that the photoperiodic control of cell
      division is mediated through the circadian clock. However, the underlying
      mechanisms remain unknown. We have studied the molecular basis of light-dependent
      control of cell division in the unicellular green alga Ostreococcus. We found
      that cell division obeys a circadian oscillator in Ostreococcus. We provide
      evidence suggesting that the clock may, at least in part, regulate directly cell
      division independently of the metabolism. Combined microarray and quantitative
      real-time reverse transcription-polymerase chain reaction analysis of the main
      core cell cycle gene expression revealed an extensive transcriptional regulation
      of cell division by the photoperiod in Ostreococcus. Finally, transcription of
      the main core cell cycle genes, including cyclins and cyclin-dependent kinases,
      was shown to be under circadian control in Ostreococcus, suggesting that these
      genes are potential targets of the circadian clock in the control of cell
      division.

PMID- 17535825
TI  - Inositol 1,3,4,5,6-pentakisphosphate 2-kinase from maize: molecular and
      biochemical characterization.
AB  - Inositol 1,3,4,5,6-pentakisphosphate 2-kinase, an enzyme encoded by the gene
      IPK1, catalyzes the terminal step in the phytic acid biosynthetic pathway. We
      report here the isolation and characterization of IPK1 cDNA and genomic clones
      from maize (Zea mays). DNA Southern-blot analysis revealed that ZmIPK1 in the
      maize genome constitutes a small gene family with two members. Two nearly
      identical ZmIPK1 paralogs, designated as ZmIPK1A and ZmIPK1B, were identified.
      The transcripts of ZmIPK1A were detected in various maize tissues, including
      leaves, silks, immature ears, seeds at 12 d after pollination, midstage
      endosperm, and maturing embryos. However, the transcripts of ZmIPK1B were
      exclusively detected in roots. A variety of alternative splicing products of
      ZmIPK1A were discovered in maize leaves and seeds. These products are derived
      from alternative acceptor sites, alternative donor sites, and retained introns in
      the transcripts. Consequently, up to 50% of the ZmIPK1A transcripts in maize
      seeds and leaves have an interrupted open reading frame. In contrast, only one
      type of splicing product of ZmIPK1B was detected in roots. When expressed in
      Escherichia coli and subsequently purified, the ZmIPK1 enzyme catalyzes the
      conversion of myo-inositol 1,3,4,5,6-pentakisphosphate to phytic acid. In
      addition, it is also capable of catalyzing the phosphorylation of myo-inositol
      1,4,6-trisphosphate, myo-inositol 1,4,5,6-tetrakisphosphate, and myo-inositol
      3,4,5,6-tetrakisphosphate. Nuclear magnetic resonance spectroscopy analysis
      indicates that the phosphorylation product of myo-inositol 1,4,6-trisphosphate is
      inositol 1,2,4,6-tetrakisphosphate. Kinetic studies showed that the K(m) for
      ZmIPK1 using myo-inositol 1,3,4,5,6-pentakisphosphate as a substrate is 119
      microm with a V(max) at 625 nmol/min/mg. These data describing the tissue
      specific accumulation and alternative splicing of the transcripts from two nearly
      identical ZmIPK1 paralogs suggest that maize has a highly sophisticated
      regulatory mechanism controlling phytic acid biosynthesis.

PMID- 17535826
TI  - Is there any relationship between asthma and asthma attack in children and
      atypical bacterial infections; Chlamydia pneumoniae, Mycoplasma pneumoniae and
      Helicobacter pylori.
AB  - Asthma is a chronic inflammatory airway disease characterized by variable airway
      obstruction and bronchial hyperresponsiveness. There are many factors affecting
      the development and severity of childhood asthma such as genetic predisposition,
      atopy, environmental factors, obesity, diet, socioeconomic status, and infectious
      triggers. In the present study we aimed to investigate the frequency of
      Mycdoplasma pneumoniae, Chlamydia pneumoniae, and Helicobacter pylori infections
      in asthmatic children. We investigated also whether there is a relationship
      between these agents and asthma attacks. MATERIAL AND METHODS: Seventy-nine
      asthmatic children (46 males, aged 5-15 years) were included in study. The study
      group was divided into two groups: group 1 consisted of 37 children with asthma
      attacks and group 2 consisted of 42 children with stable asthma. As a control
      group we studied 36 healthy children. Pulmonary function tests, skin prick tests
      for common allergens were performed; serum total IgE, phadiatop, specific IgM and
      IgG antibody levels (ELISA) for M. pneumoniae, C. pneumoniae and H. pylori were
      measured in all patients. RESULTS: Mycoplasma IgM and Chlamidia IgM were positive
      in 8.1% (3 patients) and 18.9% (7 patients) of group 1 patients, respectively.
      There was a statistically significant difference for Mycoplasma IgM (p = 0.031)
      and Chlamidia IgM (p = 0.03) between group1 and other two groups. We have not
      found significant difference for M. pneumoniae IgG, C. pneumoniae IgG and H.
      pylori IgM and IgG among groups. CONCLUSION: M. Pneumoniae and C. Pneumoniae may
      play a role in development of asthma exacerbations in childhood. We could not
      find a relationship between H. Pylori and asthma.

PMID- 17535827
TI  - Role of steroids on the clinical course and outcome of meconium aspiration
      syndrome-a randomized controlled trial.
AB  - BACKGROUND: Meconium aspiration syndrome (MAS) is one of the major causes of
      severe respiratory distress in the newborn and there is no uniform protocol of
      management after the development of MAS. OBJECTIVE: The objective of the study
      was to determine whether systemic and inhalational steroid therapy can alter the
      clinical course of MAS and improve the outcome without causing any serious
      adverse effects. METHODS: A randomized controlled trial was conducted in three
      groups of MAS over a period of 1 year. Group A (n = 33) served as controls, Group
      B (n = 34) received systemic methyl prednisolone and Group C (n = 32) received
      nebulized budesonide both for a period of 7 days starting after 24 h of age.
      Details of clinical progress were noted during the hospital stay. Follow up for a
      minimum period of 3 months was done in all. Data were analysed by SPSS 10
      software. Student's t and ANOVA were used to assess statistical significance.
      RESULTS: Patient profile was similar in all the three groups. Period of oxygen
      dependency and duration of hospital stay was significantly less in the steroid
      treated groups. Similarly full enteral feeding and radiological clearance of
      chest could be achieved earlier in groups B and C. No difference between the
      steroid treated groups could be appreciated by Student's Newman Kuel (SNK) test.
      Development of sepsis was similar in all the groups and no serious adverse
      effects were noted in steroid treated groups. CONCLUSION: Steroids are effective
      in the management of MAS and route of administration does not have a bearing on
      the efficacy.

PMID- 17535829
TI  - Limitations in the National Cancer Institute antitumor drug screening database
      for evaluating hormesis.

PMID- 17535830
TI  - Re: "Chromosomal aberrations and cancer risk: results of a cohort study from
      central Europe".

PMID- 17535831
TI  - A meta-analysis of the association of N-acetyltransferase 2 gene (NAT2) variants
      with breast cancer.
AB  - The N-acetyltransferase 2 gene (NAT2) product is an enzyme important in
      carcinogen metabolism via activation and detoxification pathways. Therefore, NAT2
      variants may represent underlying susceptibility to breast cancer. Because a
      number of studies of the association of NAT2 with breast cancer have been
      published, the authors performed a meta-analysis. They extracted all relevant
      data to examine evidence for a main effect (i.e., the effect in a model that does
      not include any interactions) of NAT2 phenotype and genotype on breast cancer
      risk. They summarized the evidence for modification by smoking and meat intake,
      sources of exposure to aromatic and heterocyclic amines, respectively, which are
      metabolized by NAT2. The authors identified seven studies that measured NAT2
      phenotype and 20 studies that deduced phenotype via genotyping. They found no
      evidence for heterogeneity (Cochran's Q statistic p=0.74) and no statistically
      significant increased risk from NAT2 acetylation (slow/rapid) for breast cancer
      (summary odds ratio=1.02, 95% confidence interval: 0.95, 1.08). These results
      suggest that there is no overall association between the NAT2 slow- or rapid
      acetylation phenotype and breast cancer risk. However, some evidence suggests
      that smoking may modify this association.

PMID- 17535832
TI  - Novel mutations of ND genes in complex I deficiency associated with mitochondrial
      encephalopathy.
AB  - Isolated Complex I (CI) deficiency, the most frequent cause of mitochondrial
      disease, is a clinically and genetically heterogeneous condition. Complex I is a
      giant multiheteromeric enzyme composed of seven ND subunits encoded by
      mitochondrial DNA (mtDNA) genes, and at least 38 subunits encoded by nuclear
      genes. To establish the contribution to human mitochondrial encephalopathy of ND
      versus nuclear gene mutations, we have been undertaking a systematic analysis of
      CI genes in a cohort of 46 adult and paediatric patients with biochemically
      defined CI defect. Sequence analysis of the entire mtDNA let us identify six
      patients with mutations in ND genes. The clinical presentations varied, from
      infantile Leigh syndrome, to childhood MELAS, to adult-onset encephalopathic
      syndromes of variable severity. Three of the mutations were not previously
      reported (3481G > A, 14600G > A and 13063G > A, in ND1, ND6 and ND5 genes,
      respectively) and were further investigated in mutant transmitochondrial cybrids.
      Tight correlation between mutation load and decrease in CI activity was observed
      in each of the three mutant cybrid lines, supporting the pathogenic role of the
      novel mutations. Structural studies on mutant cybrids showed impaired assembly or
      reduced stability of the holoenzyme complex. In our experience ND gene mutations
      are relatively common in CI-defective mitochondrial encephalopathy of both
      children and adults.

PMID- 17535833
TI  - Mechanisms of body weight gain in patients with Parkinson's disease after
      subthalamic stimulation.
AB  - Chronic bilateral subthalamic stimulation leads to a spectacular clinical
      improvement in patients with motor complications. However, the post-operative
      body weight gain involved may limit the benefits of surgery and induce critical
      metabolic disorders. Twenty-four Parkinsonians (61.1 +/- 1.4 years) were examined
      1 month before (M - 1) and 3 months after (M + 3) surgery. Body composition and
      energy expenditure (EE) were measured (1) over 36 h in calorimetric chambers (CC)
      with rigorous control of food intakes and activities [sleep metabolic rate,
      resting activities, meals, 3 or 4 sessions of 20 min on a training bicycle at 13
      km/h and daily EE] and (2) in resting conditions (basal metabolic rate) during an
      acute L-dopa challenge (M - 1) or according to acute 'off' and 'on' stimulation
      (M + 3). Before surgery, EE was compared between the Parkinsonian patients and
      healthy subjects matched for height and body composition (metabolic rate during
      sleep, daily EE) or matched to predicted values (basal metabolic rate). Before
      surgery, in Parkinsonian men but not women, (1) daily EE was higher while sleep
      metabolic rate was lower compared to healthy matched men (+9.2 +/- 3.9 and -8.2
      +/- 2.3%, respectively, P < 0.05) and (2) basal metabolic rate (L-dopa 'on') was
      higher than predicted basal metabolic rate (+11.5 +/- 4.0%, P < 0.05) but was
      further increased without L-dopa (+8.4 +/- 3.2% vs L-dopa 'on', P < 0.05). EE
      during daily activities was higher during 'off' periods compared to 'on' periods
      for both men (+19.3 +/- 3.3%, P < 0.0001) and women (+16.1 +/- 4.7%, P < 0.01).
      After surgery, there was a 3.4 +/- 0.6 kg (P < 0.0001) body weight increase
      together with fat mass (P < 0.0001) and fat-free mass (P < 0.05) in Parkinsonian
      men and a 2.6 +/- 0.8 kg (P < 0.05) body weight increase together with fat mass
      (P < 0.05) in Parkinsonian women. Sleep metabolic rate increased in men (+7.5 +/-
      2.0%, P < 0.01) to reach control values but remained unchanged in women. Daily EE
      decreased significantly in both men and women (-7.3 +/- 2.2% and -13.1 +/- 1.7%,
      respectively, P < 0.01) but there was no correlation between daily EE changes and
      body weight gain. Parkinson's disease is associated with profound alterations in
      the central control of energy metabolism. Normalization of energy metabolism
      after DBS-STN implantation may favour body weight gain, of which quality was
      gender specific. As men gained primarily fat-free mass, a reasonable weight gain
      may be tolerated, in contrast with women who gained only fat. Other factors such
      as changes in free-living physical activity may help to limit body weight gain in
      some patients.

PMID- 17535834
TI  - Evolution of cognitive dysfunction in an incident Parkinson's disease cohort.
AB  - We have previously performed detailed clinical and neuropsychological assessments
      in a community-based cohort of patients with newly diagnosed parkinsonism, and
      through analysis of a subcohort with idiopathic Parkinson's disease (PD), we have
      demonstrated that cognitive dysfunction occurs even at the time of PD diagnosis
      and is heterogeneous. Longitudinal follow-up of the cohort has now been performed
      to examine the evolution of cognitive dysfunction within the early years of the
      disease. One hundred and eighty (79%) eligible patients from the original cohort
      with parkinsonism were available for re-assessment at between 3 and 5 years from
      their initial baseline assessments. PD diagnoses were re-validated with repeated
      application of the UKPDS Brain Bank criteria in order to maximize sensitivity and
      specificity, following which a diagnosis of idiopathic PD was confirmed in 126
      patients. Thirteen out of 126 (10%) had developed dementia at a mean (SD) of 3.5
      (0.7) years from diagnosis, corresponding to an annual dementia incidence of 30.0
      (16.4-52.9) per 1000 person-years. A further 57% of PD patients showed evidence
      of cognitive impairment, with frontostriatal deficits being most common amongst
      the non-demented group. However, the most important clinical predictors of global
      cognitive decline following correction for age were neuropsychological tasks with
      a more posterior cortical basis, including semantic fluency and ability to copy
      an intersecting pentagons figure, as well as a non-tremor dominant motor
      phenotype at the baseline assessment. This work clarifies the profile of
      cognitive dysfunction in early PD and demonstrates that the dementing process in
      this illness is heralded by both postural and gait dysfunction and cognitive
      deficits with a posterior cortical basis, reflecting probable non-dopaminergic
      cortical Lewy body pathology. Furthermore, given that these predictors of
      dementia are readily measurable within just a few minutes in a clinical setting,
      our work may ultimately have practical implications in terms of guiding prognosis
      in individual patients.

PMID- 17535835
TI  - In vivo assessment of cervical cord damage in MS patients: a longitudinal
      diffusion tensor MRI study.
AB  - Cervical cord damage is likely to contribute to the accumulation of disability in
      multiple sclerosis (MS) and can be quantified in vivo using MRI. We used
      conventional and diffusion tensor (DT) MRI to: (a) define the temporal evolution
      of intrinsic tissue injury and atrophy in the cervical cord from MS patients, (b)
      investigate how these two aspects of cord damage are interrelated and (c) assess
      the correlation of cord MRI metrics with concomitant brain damage and disability.
      Conventional and DT MRI of the brain and cervical cord were obtained from 42 MS
      patients and 9 healthy controls at baseline and after a mean follow-up of 2.4
      years. At each time-point, we measured: cervical cord lesion number, cross
      sectional area, mean diffusivity (MD) and fractional anisotropy (FA). Brain T2
      lesion volume, grey matter MD, normal appearing white matter (NAWM) MD and FA, as
      well as longitudinal normalized percentage brain volume changes were also
      measured. In MS patients, cervical cord cross-sectional area (P < 0.001) and FA
      (P = 0.01) decreased, and cervical cord MD increased (P < 0.001) during follow
      up. Cord FA decrease, but not cord cross-sectional area and MD, was significantly
      higher (P = 0.05) in primary progressive MS patients than in those with either
      relapsing-remitting or secondary progressive MS. At baseline and follow-up,
      moderate correlations were found between intrinsic cord diffusivity abnormalities
      and cord cross-sectional area (r values ranging from 0.34 to 0.58), but not
      between their changes over time. No cross-sectional and longitudinal correlations
      were found between these MRI metrics and the number of cord T2-visible lesions.
      Brain NAWM MD (P = 0.03) and brain volume (P < 0.001) also changed in patients.
      There was no significant correlation between cord and brain MRI metrics at both
      time-points, as well as between their changes occurred over the follow-up.
      Baseline cord cross-sectional area (r = -0.40, P = 0.01) and FA (r = -0.40, P =
      0.03) correlated with increase in disability at follow-up. This study shows that
      both progressive tissue loss and injury to the remaining tissue occur in the
      cervical cord of MS patients, and that these two components of cord damage are
      not strictly interrelated, thus suggesting that a multiparametric MRI approach is
      needed to achieve more accurate estimates of such a damage. MS cord pathology
      also seems to be independent of concomitant brain changes, to develop at
      different rates according to disease phenotype, and to be associated to medium
      term disability accrual.

PMID- 17535836
TI  - Ictal clinical and scalp-EEG findings differentiating temporal lobe epilepsies
      from temporal 'plus' epilepsies.
AB  - Temporal 'plus' epilepsies are characterized by seizures involving a complex
      epileptogenic network including the temporal lobe and the closed neighboured
      structures such as the orbito-frontal cortex, the insula, the frontal and
      parietal operculum and the temporo-parieto-occipital junction. Temporal 'plus'
      epilepsies are currently identified by means of intracerebral electrodes but
      whether their diagnosis can be suspected non-invasively has not been evaluated
      yet. The aim of this retrospective study was to address this issue in 80
      consecutive patients who were thought to suffer from non-lesional temporal lobe
      seizures which finally proved, on the basis of stereotactic intracerebral EEG
      (SEEG) recordings, to be 'purely' temporal (TL group, n = 58) or temporal 'plus'
      (T+ group, n = 22). Our results showed that the two groups of patients were
      difficult to differentiate on the basis of general clinical features or MRI data.
      Even the presence of hippocampal sclerosis did not distinguish the two groups.
      Conversely, both ictal clinical symptoms and scalp-EEG findings significantly
      differentiated TL from T+ patients. Patients with TL epilepsies more frequently
      presented an ability to warn at seizure onset (P = 0.003), an abdominal aura (P =
      0.05), gestural automatisms (P = 0.04) and a post-ictal amnesia (P = 0.02).
      Patients suffering from T+ epilepsies more frequently had gustatory
      hallucinations (P = 0.02), rotatory vertigo (P = 0.02) and auditory illusions (P
      = 0.02) at seizure onset; they exhibited more frequently contraversive
      manifestations of the eyes and/or head (P = 0.001), piloerection (P = 0.03) and
      ipsilateral tonic motor signs (P = 0.05), and they were more often dysphoric in
      the post-ictal phase (P = 0.0001). Cluster analysis mainly indicated that some
      associations of symptoms were relevant for differentiating TL cases from T+
      cases. Interictal EEG of T+ patients more frequently exhibited bilateral or
      precentral abnormalities, while ictal EEG more frequently pointed over the
      anterior frontal, temporo-parietal and precentral regions. Neither TL interictal
      spikes, nor TL ictal EEG onset, allowed us definitely to rule out the possibility
      of T+ epilepsies. Our findings may be useful for identifying, among patients
      suffering from 'atypical' non-lesional TL epilepsies, those who should undergo
      invasive recordings before surgery.

PMID- 17535837
TI  - Spontaneous intracranial hypotension with deep brain swelling.
AB  - Spontaneous intracranial hypotension (SIH) is caused by leakage of CSF, and
      characterized on MRI by brain sagging, dilatation of veins and dural sinuses,
      subdural fluid collections and post-contrast enhancement of the thickened dura. A
      few cases may present a very severe brain sagging through the tentorial notch and
      swelling of the diencephalic-mesencephalic structures, with absent or scarce
      subdural collections and post-contrast enhancement. These patients may have
      surprisingly few neurological signs or may become drowsy and even lapse into coma
      due to central herniation. We retrospectively examined the diffusion studies
      obtained in five patients with these MRI findings, in seven patients with SIH
      without brain swellings and in ten controls. Mean diffusivity was increased in
      SIH patients with brain swelling in areas draining into the deep venous system,
      collected by the vein of Galen (vG) and straight sinus (SS). In the hypothesis
      that central herniation might be responsible for venous stagnation because of
      impaired flow of the vG into the SS, the vG/SS angle was measured. The angle
      formed by the vG entering the SS was not altered in patients without brain
      swelling (group E, 67.8 degrees +/- 10.3 degrees, mean +/- SD, range 49-80
      degrees) when compared to controls (group C, 73.3 degrees +/- 12.3 degrees, mean
      +/- SD, range 56-95 degrees). It was, however, grossly decreased in patients with
      brain swelling (group D, 40.7 degrees +/- 12.8 degrees, mean +/- SD, range 22-61
      degrees), P < 0.001 for comparison with groups E and C. As suggested by previous
      studies, downward stretching of the vG and narrowing of the vG/SS angle may cause
      a functional stenosis at the vG-SS junction. We suggest that in the application
      of the Monro-Kellie doctrine to SIH, the brain volume should not be considered as
      always invariable.

PMID- 17535838
TI  - The physiologist and the neurosurgeon: the enduring influence of Charles
      Sherrington on the career of Wilder Penfield.
AB  - Wilder Penfield, a Rhodes scholar from Princeton University, New Jersey, was a
      student in the first course on mammalian physiology given in 1915 at Oxford
      University by Charles Sherrington, newly arrived from Liverpool where, as Holt
      Professor of Physiology for 20 years, he had become a leading authority on the
      physiology of the nervous system. The practical 'exercises' as well as graduate
      research on the Golgi apparatus and the decerebrate preparation, carried out by
      Penfield in Sherrington's laboratory, gave him the groundwork to develop his
      career as a physiological surgeon, who made fundamental observations on
      functional localization in the human brain during the surgical treatment of
      patients afflicted with epilepsy.

PMID- 17535839
TI  - An analysis of factors that predict patient consent to take part in a randomized
      controlled trial.
AB  - BACKGROUND: Recruitment targets of patients to multi-centre primary care-based
      randomized controlled trials (RCT) are often not met. A critical step in the
      pathway is whether an eligible patient will give consent. OBJECTIVE: To assess
      whether patient, practice or practitioner characteristics are associated with a
      patient's likelihood of giving consent to participation in a large primary care
      based RCT. METHODS: A cross-sectional study of patients from 260 practices in
      England and Wales who met the eligibility criteria for an RCT of aspirin versus
      warfarin for stroke prevention and attended an appointment with their GP to
      consider trial participation. Logistic regression analysis was used to determine
      which patient and practitioner factors independently predicted whether or not a
      patient would give consent to take part in the trial. RESULTS: Of the 1740
      patients, 973 (55.9%) gave consent. On multivariable analysis, patient factors
      associated with increased likelihood of giving consent were younger age, current
      use of warfarin and year of recruitment to the trial. Patients with a history of
      transient ischaemic attack, angina or valve disease were less likely to give
      consent. Practice/practitioner factors that were associated with increased
      likelihood of consent were smaller practice size (practices with greater than
      eight GPs as compared with those with one to two GPs, odds ratio 0.40, 95%
      confidence interval 0.21-0.75) and older GPs. CONCLUSIONS: The strong association
      of consent with year of recruitment may be due to changes in trial procedures and
      investigator training. If so, this has important implications for the conduct of
      future trials.

PMID- 17535840
TI  - Leflunomide and methotrexate combination in refractory adult-onset Still's
      disease.

PMID- 17535841
TI  - Exogenous Cushing syndrome with inhaled fluticasone in a child receiving
      lopinavir/ritonavir.
AB  - OBJECTIVE: To describe a case of Cushing syndrome in a child during concurrent
      use of inhaled fluticasone propionate, nasal mometasone, and a highly active
      antiretroviral regimen including lopinavir/ritonavir. CASE SUMMARY: A 9-year-old
      boy with HIV infection and asthma developed moon facies, increased facial hair,
      and increased weight after fluticasone propionate inhalation (1 puff; 220 microg)
      therapy was begun. His antiretroviral regimen contained the protease inhibitor
      combination lopinavir/ritonavir at a dose of 216/54 mg twice daily, and he had
      been stable for the previous 5 years. He had also been receiving intranasal
      mometasone for 11 months for the management of allergic rhinitis. Serum cortisol
      and adrenocorticotropic hormone levels were consistent with adrenal suppression.
      These physical findings and symptoms and laboratory values normalized after
      discontinuation of the fluticasone propionate. The Naranjo probability scale
      indicated that a probable interaction occurred between lopinavir/ritonavir and
      fluticasone propionate, leading to subsequent adrenal suppression. DISCUSSION:
      Protease inhibitors are associated with numerous drug interactions due to
      inhibition of the CYP3A4 isoenzyme. Pharmaceutical agents used to treat
      comorbidities in HIV-infected individuals often can interact with protease
      inhibitors, leading to toxic drug concentrations or untoward effects. Inhaled
      corticosteroids such as fluticasone propionate are often necessary to treat
      asthma in young children and are metabolized by CYP3A4. Interactions between
      protease inhibitors and inhaled fluticasone propionate have been reported in the
      adult population, but reports are limited in the pediatric literature.
      CONCLUSIONS: This case raises awareness of the interaction between fluticasone
      propionate and lopinavir/ritonavir and adverse effects in children receiving both
      medications.

PMID- 17535842
TI  - Oral antidiabetic agents in pregnancy and lactation: a paradigm shift?
AB  - OBJECTIVE: To provide information on the use of oral antidiabetic agents in
      pregnancy and breast-feeding. DATA SOURCES: Primary articles were identified by a
      MEDLINE search (1966-March 2007) using the MeSH headings: pregnancy in diabetics,
      pregnancy, polycystic ovary syndrome, hypoglycemic agents, glipizide, glyburide,
      metformin, rosiglitazone, pioglitazone, clinical trial, controlled clinical
      trial, multicenter study, randomized controlled trial, case-control studies, and
      cohort studies. STUDY SELECTION AND DATA EXTRACTION: All studies using oral
      antidiabetic agents in pregnancy were evaluated and relevant data were included
      in the discussion. DATA SYNTHESIS: Studies of glyburide and glipizide have found
      little or no transfer of these drugs across the placenta, whereas metformin and
      rosiglitazone cross readily. Animal studies have found no evidence to suggest
      that glyburide, glipizide, metformin, or rosiglitazone are teratogenic. In
      gestational diabetes, glyburide was safe and efficacious; however, 16-19% of
      women failed to achieve optimal glucose control. No developmental toxicity in
      infants was observed when metformin was used before and throughout pregnancy in
      women with polycystic ovarian syndrome (PCOS). Some of the studies involving
      patients with type 2 diabetes had methodological problems. A randomized
      controlled trial using metformin for gestational diabetes in the third trimester
      is underway. The human information is inadequate to evaluate the risk of
      glipizide or the thiazolidinediones in pregnancy. In breast milk, 3 studies
      measured nonsignificant amounts of metformin and one study was unable to detect
      either glyburide or glipizide. CONCLUSIONS: Neither glyburide nor metformin has
      caused developmental toxicity in humans. Glyburide has been used for the
      treatment of gestational diabetes, and metformin has been used in women with PCOS
      who eventually became pregnant. Additional trials are needed to better define the
      benefits and risks of oral antidiabetic agents in pregnancy. Metformin,
      glyburide, and glipizide appear to be compatible with breast-feeding.

PMID- 17535843
TI  - Preemptive therapy in nonneutropenic patients with Candida infection using the
      Japanese guidelines.
AB  - BACKGROUND: The Japanese Guidelines for the Diagnosis and Treatment of Deep
      Seated Mycosis were established in 2003. Proven Candida infection (CI) is defined
      as at least one positive blood culture yielding a Candida species. Clinically
      documented CI requires documentation of more than 2 sites of colonization and a
      positive plasma beta-D-glucan test. Possible CI is diagnosed by one of the above
      criteria in febrile, nonneutropenic critically ill patients. OBJECTIVE: To assess
      the use of definitions of clinically documented and possible CI for guiding
      preemptive antifungal therapy in critically ill patients. METHODS: The patients
      treated in our intensive care unit (ICU) for at least 48 hours between 2000 and
      2004 were investigated. The administration of antifungal agents and ICU mortality
      were compared among proven, clinically documented, and possible CI groups for
      age, sex, APACHE II score, diagnosis, length of ICU stay, treatment, number of
      colonization sites, and plasma beta-D-glucan level. RESULTS: Six patients were
      diagnosed with proven CI, 25 were diagnosed with clinically documented CI, and
      104 with possible CI. The patients with clinically documented CI were compared
      with those with possible CI, and statistically significant differences were found
      in the following variables: APACHE II score (p = 0.018), length of ICU stay (p <
      0.01), use of ventilator (p = 0.027), tracheotomy (p = 0.027), number of
      colonization sites (p < 0.001), plasma beta-D-glucan level (p < 0.001), and
      administration of antifungal agents (p < 0.001); incidence of mortality was not
      statistically significant (p = 0.33). The shorter length of ICU stay, use of
      ventilator, and continuous hemodiafiltration were risk factors for death after
      adjusting for APACHE II score, admission before/after 2003, antifungal therapy,
      and other factors. Although the frequency of the administration of preemptive
      antifungal therapy was higher after 2003 than before, the mortality rate did not
      differ significantly. CONCLUSIONS: The use of the definitions of clinically
      documented and possible CI may be beneficial for determining when it is
      appropriate to initiate preemptive antifungal therapy. However, use of the
      guidelines did not lead to prevention of possible CI proceeding to clinically
      documented CI or to improved mortality.

PMID- 17535844
TI  - Use of histamine2-antagonists for the treatment of verruca vulgaris.
AB  - OBJECTIVE: To review the evidence for histamine2 (H2)-antagonists in the
      treatment of common warts. DATA SOURCES: Relevant publications were identified
      through a systematic search of PubMed English-language literature using the MeSH
      terms and key words cimetidine, ranitidine, famotidine, nizatidine, histamine H2
      antagonists, and warts. Additional articles were identified using the same key
      words in the Cochrane Database and International Pharmaceutical Abstracts.
      Systematic searches were conducted through January 2007. In addition, pertinent
      references from identified articles were reviewed. STUDY SELECTION AND DATA
      EXTRACTION: The literature search retrieved 21 relevant citations, excluding
      review articles. Five open-label studies and 7 randomized controlled clinical
      trials were evaluated. Cimetidine was the focus of 11 studies, and ranitidine was
      evaluated in 1 study. No data regarding the other H2-antagonists were found. The
      other retrieved citations were not evaluated due to their design (case reports or
      case series) and/or focus on specific wart subtypes, not common warts. DATA
      SYNTHESIS: The use of H2-antagonists in the treatment of common warts is not
      associated with significant improvements in resolution rates. Open-label studies
      were promising with an estimated 48-81% response rate. However, randomized
      controlled trials have failed to show significant efficacy when cimetidine was
      compared with placebo or topical agents, and ranitidine has never been evaluated
      in a randomized controlled trial. Adverse effects, specifically gastrointestinal
      complaints, were documented. Efficacy may have been limited by inadequate dosing
      in some of the trials. The studies were limited by the small sample size and lack
      of power in a number of the trials, as well as the documented spontaneous
      resolution rate for warts. CONCLUSIONS: Several open-label trials evaluating the
      use of H2-antagonists for verruca vulgaris reported high response rates, but
      these results have not been corroborated by more rigorous clinical trials.
      Current data do not support the use of H2-antagonists for the treatment of common
      warts.

PMID- 17535845
TI  - Travel-associated acquisition of hepatitis C virus infection in patients
      receiving haemodialysis.
AB  - BACKGROUND: It has been proposed that hepatitis C virus (HCV)-infected patients
      with end-stage renal disease undergoing maintenance haemodialysis may lack HCV
      antibody (anti-HCV) despite chronic HCV viraemia. This carries important
      implications for the design of surveillance policies. METHODS: To characterize
      the prevalence of antibody-negative/RNA-positive HCV infection, patients
      attending seven haemodialysis units underwent anti-HCV testing using a third
      generation assay and HCV RNA testing using real-time PCR. RESULTS: At screening,
      anti-HCV prevalence was 12/360 (3.3%; 95% CI 1.7-5.8%); 7/12 (58.3%) anti-HCV
      positive samples were HCV RNA positive. Among anti-HCV-negative samples, 2/348
      (0.6%; 95% CI 0.2-2.1%) tested HCV RNA positive (genotype 1a). Retrospective
      testing of stored sera dated the infections to a period of holiday in the Indian
      subcontinent. The two infections were unrelated by HCV-NS5B sequencing. Only one
      of the two newly infected persons showed raised transaminases. Both developed
      anti-HCV within 8-13 weeks of follow-up. Prospective surveillance of travellers
      to resource-limited countries returning to the units showed a HCV incidence of
      4/153 travel episodes (2.6%; 95% CI 0.7-6.6%) among 131 persons (3.1%; 95% CI 0.8
      7.6%). CONCLUSIONS: Among haemodialysis patients in the United Kingdom, antibody
      negative/RNA-positive HCV status is associated with newly acquired infection,
      rather than lack of antibody responses in chronic HCV infection. There is a
      significant risk of HCV infection associated with travel to resource-limited
      countries. Given that transaminase levels may be normal, HCV RNA testing is
      recommended in patients re-entering a dialysis unit following haemodialysis in
      settings where suboptimal infection control policies pose a risk of exposure to
      blood-borne viruses.

PMID- 17535846
TI  - Nucleolin functions in nucleolus formation and chromosome congression.
AB  - A complex structure, designated the chromosome periphery, surrounds each
      chromosome during mitosis. Although several proteins have been shown to localize
      to the chromosome periphery, their functions during mitosis remain unclear. Here,
      we used a combination of high-resolution microscopy and RNA-interference-mediated
      depletion to study the functions of nucleolin, a nucleolar protein localized at
      the chromosome periphery, in interphase and mitosis. During mitosis, nucleolin
      was localized in the peripheral region including the vicinity of the outer
      kinetochore of chromosomes. Staining with an antibody specific for nucleolin
      phosphorylated by CDC2 revealed that nucleolin was also associated with the
      spindle poles from prometaphase to anaphase. Nucleolin depletion resulted in
      disorganization of the nucleoli at interphase. Furthermore, nucleolin-depleted
      cells showed a prolonged cell cycle with misaligned chromosomes and defects in
      spindle organization. The misaligned chromosomes showed syntelic kinetochore
      microtubule attachments with reduced centromere stretching. Taken together, our
      results indicate that nucleolin is required for nucleolus formation, and is also
      involved in chromosome congression and spindle formation.

PMID- 17535847
TI  - High-pressure freezing provides insights into Weibel-Palade body biogenesis.
AB  - The Weibel-Palade bodies (WPBs) of endothelial cells play an important role in
      haemostasis and the initiation of inflammation, yet their biogenesis is poorly
      understood. Tubulation of their major content protein, von Willebrand factor
      (VWF), is crucial to WPB function, and so we investigated further the
      relationship between VWF tubule formation and WPB formation in human umbilical
      vein endothelial cells (HUVECs). By using high-pressure freezing and freeze
      substitution before electron microscopy, we visualised VWF tubules in the trans
      Golgi network (TGN), as well as VWF subunits in vesicular structures. Tubules
      were also seen in WPBs that were connected to the TGN by membranous stalks.
      Tubules are disorganised in the immature WPBs but during maturation we found a
      dramatic increase in the spatial organisation of the tubules and in organelle
      electron density. We also found coated budding profiles suggestive of the removal
      of missorted material after initial formation of these granules. Finally, we
      discovered that these large, seemingly rigid, organelles flex at hinge points and
      that the VWF tubules are interrupted at these hinges, facilitating organelle
      movement around the cell. The use of high-pressure freezing was vital in this
      study and it suggests that this technique might prove essential to any detailed
      characterisation of organelle biogenesis.

PMID- 17535848
TI  - Non-classical export of epimorphin and its adhesion to alphav-integrin in
      regulation of epithelial morphogenesis.
AB  - Epimorphin (also known as syntaxin 2) acts as an epithelial morphogen when
      secreted by stromal cells of the mammary gland, lung, liver, colon, pancreas and
      other tissues, but the same molecule functions within the cell to mediate
      membrane fusion. How this molecule, which lacks a signal sequence and contains a
      transmembrane domain at the C-terminus, translocates across the plasma membrane
      and is secreted to become a morphogen, and how it initiates morphogenic events is
      not clear. Here, we show that epimorphin is secreted through a non-classical
      mechanism, similar to that previously described for secretion of the leaderless
      protein FGF1, and we identify the key molecular elements responsible for
      translocation and secretion from the cell. We also show that secreted epimorphin
      binds to alphav-integrin-containing receptors on target epithelial cells, leading
      to activation of specific downstream signaling pathways and induction of
      epithelial morphogenesis. These findings provide key insight into how epimorphin
      functions as an epithelial morphogen.

PMID- 17535849
TI  - A unique and specific interaction between alphaT-catenin and plakophilin-2 in the
      area composita, the mixed-type junctional structure of cardiac intercalated
      discs.
AB  - Alpha-catenins play key functional roles in cadherin-catenin cell-cell adhesion
      complexes. We previously reported on alphaT-catenin, a novel member of the alpha
      catenin protein family. alphaT-catenin is expressed predominantly in
      cardiomyocytes, where it colocalizes with alphaE-catenin at the intercalated
      discs. Whether alphaT- and alphaE-catenin have specific or synergistic functions
      remains unknown. In this study we used the yeast two-hybrid approach to identify
      specific functions of alphaT-catenin. An interaction between alphaT-catenin and
      plakophilins was observed and subsequently confirmed by co-immunoprecipitation
      and colocalization. Interaction with the amino-terminal part of plakophilins
      appeared to be specific for the central ;adhesion-modulation' domain of alphaT
      catenin. In addition, we showed, by immuno-electron microscopy, that desmosomal
      proteins in the heart localize not only to the desmosomes in the intercalated
      discs but also at adhering junctions with hybrid composition. We found that in
      the latter junctions, endogenous plakophilin-2 colocalizes with alphaT-catenin.
      By providing an extra link between the cadherin-catenin complex and intermediate
      filaments, the binding of alphaT-catenin to plakophilin-2 is proposed to be a
      means of modulating and strengthening cell-cell adhesion between cardiac muscle
      cells. This could explain the devastating effect of plakophilin-2 mutations on
      cell junction stability in intercalated discs, which lead to cardiac muscle
      malfunction.

PMID- 17535850
TI  - Regulated Nodal signaling promotes differentiation of the definitive endoderm and
      mesoderm from ES cells.
AB  - Nodal signaling induces the formation of the endoderm and mesoderm during
      gastrulation. Nodal expression persists until the definitive endoderm progenitor
      has completely formed, and disappears thereafter. A tightly regulated Nodal
      expression system is essential for the differentiation of embryonic stem (ES)
      cells into distinct tissue lineages. On this basis, we established an ES cell
      differentiation system with the tetracycline-regulated expression of Nodal. The
      upregulated Nodal signaling pathway and its downstream transcriptional targets
      induced the specification of ES cells into definitive endoderm and mesoderm
      derivatives, and the subsequent downregulation of Nodal signaling promoted
      further maturation of the gut tube both in vitro and in vivo. Sustained
      expression of the Nodal gene inhibited the maturation of the definitive endoderm
      owing to persistent Oct3 and/or Oct4 expression and teratoma formation.
      Furthermore, quantitative single cell analysis by flow cytometry using CXCR4,
      VEGFR2 and PDGFR-alpha indicated that this protocol for definitive endoderm and
      mesoderm differentiation is superior to any other available protocol. Our
      findings also indicated that the Nodal or Nodal-related molecules secreted from
      Nodal-expressing ES cells could cause genetically unmanipulated ES cells to
      induce the expression of the Nodal signaling pathway and its downstream targets,
      which consequently leads to the differentiation of the ES cells into definitive
      endoderm and mesoderm. Our differentiation system, using tightly regulated Nodal
      expression, enabled us to investigate the mechanism of ES cell differentiation
      into definitive endoderm or mesoderm derivatives. Our findings also demonstrate
      that Nodal-expressing ES cells might be a source of highly active proteins that
      could be used for developing endoderm or mesoderm tissues in regenerative
      medicine.

PMID- 17535851
TI  - Characterization of NIP2/centrobin, a novel substrate of Nek2, and its potential
      role in microtubule stabilization.
AB  - Nek2 is a mitotic kinase whose activity varies during the cell cycle. It is well
      known that Nek2 is involved in centrosome splitting, and a number of studies have
      indicated that Nek2 is crucial for maintaining the integrity of centrosomal
      structure and microtubule nucleation activity. In the present study, we report
      that NIP2, previously identified as centrobin, is a novel substrate of Nek2. NIP2
      was daughter-centriole-specific, but was also found in association with a stable
      microtubule network of cytoplasm. Ectopic NIP2 formed aggregates but was
      dissolved by Nek2 into small pieces and eventually associated with microtubules.
      Knockdown of NIP2 showed significant reduction of microtubule organizing
      activity, cell shrinkage, defects in spindle assembly and abnormal nuclear
      morphology. Based on our results, we propose that NIP2 has a role in stabilizing
      the microtubule structure. Phosphorylation may be crucial for mobilization of the
      protein to a new microtubule and stabilizing it.

PMID- 17535853
TI  - The Drosophila muscle LIM protein, Mlp84B, cooperates with D-titin to maintain
      muscle structural integrity.
AB  - Muscle LIM protein (MLP) is a cytoskeletal LIM-only protein expressed in striated
      muscle. Mutations in human MLP are associated with cardiomyopathy; however, the
      molecular mechanism by which MLP functions is not established. A Drosophila MLP
      homolog, mlp84B, displays many of the same features as the vertebrate protein,
      illustrating the utility of the fly for the study of MLP function. Animals
      lacking Mlp84B develop into larvae with a morphologically intact musculature, but
      the mutants arrest during pupation with impaired muscle function. Mlp84B displays
      muscle-specific expression and is a component of the Z-disc and nucleus.
      Preventing nuclear retention of Mlp84B does not affect its function, indicating
      that Mlp84B site of action is likely to be at the Z-disc. Within the Z-disc,
      Mlp84B is colocalized with the N-terminus of D-titin, a protein crucial for
      sarcomere organization and stretch mechanics. The mlp84B mutants phenotypically
      resemble weak D-titin mutants. Furthermore, reducing D-titin activity in the
      mlp84B background leads to pronounced enhancement of the mlp84B muscle defects
      and loss of muscle structural integrity. The genetic interactions between mlp84B
      and D-titin reveal a role for Mlp84B in maintaining muscle structural integrity
      that was not obvious from analysis of the mlp84B mutants themselves, and suggest
      Mlp84B and D-titin cooperate to stabilize muscle sarcomeres.

PMID- 17535852
TI  - Hrk/DP5 contributes to the apoptosis of select neuronal populations but is
      dispensable for haematopoietic cell apoptosis.
AB  - The pro-apoptotic BH3-only members of the Bcl2 family, crucial initiators of cell
      death, are activated by a diverse array of developmental cues or experimentally
      applied stress stimuli. We have investigated, through gene targeting in mice, the
      biological roles for the BH3-only family member HRK (also known as DP5) in
      apoptosis regulation. Hrk gene expression was found to be restricted to cells and
      tissues of the central and peripheral nervous systems. Sensory neurons from mice
      lacking Hrk were less sensitive to apoptosis induced by nerve growth factor (NGF)
      withdrawal, consistent with the induction of Hrk following NGF deprivation. By
      contrast, cerebellar granule neurons that upregulate Hrk upon transfer to low-K+
      medium underwent apoptosis normally under these conditions in the absence of Hrk.
      Furthermore, loss of Hrk was not sufficient to rescue the neuronal degeneration
      in lurcher mutant mice. Despite previous reports, no evidence was found for Hrk
      expression or induction in growth-factor-dependent haematopoietic cell lines
      following withdrawal of their requisite cytokine, and haematopoietic progenitors
      lacking HRK died normally in response to cytokine deprivation. These results
      demonstrate that HRK contributes to apoptosis signalling elicited by trophic
      factor withdrawal in certain neuronal populations but is dispensable for
      apoptosis of haematopoietic cells.

PMID- 17535854
TI  - Does deep water running reduce exercise-induced breast discomfort?
AB  - AIM: To establish whether exercise-induced vertical breast displacement and
      discomfort in women with large breasts were reduced during deep water running
      compared to treadmill running. METHODS: Sixteen women (mean age = 32 years, range
      19-43 years; mean mass = 74.1 kg, range 61-114 kg; mean height = 1.7 m, range
      1.61-1.74 m), who were professionally sized to wear a C+ bra cup, were recruited
      as representative of women with large breasts. After extensive familiarisation,
      vertical breast motion of the participants was quantified as they ran at a self
      selected stride rate on a treadmill and in 2.4 m deep water. Immediately after
      running, the subjects rated their breast discomfort and breast pain (visual
      analogue scale) and their perceived exertion (Borg scale). Breast discomfort,
      breast pain, perceived exertion, vertical breast displacement and vertical breast
      velocity were compared between the two experimental conditions. RESULTS: Exercise
      induced breast discomfort was significantly less and perceived exertion was
      significantly greater during deep water running relative to treadmill running.
      Although there was no significant between-condition difference in vertical breast
      displacement, mean peak vertical breast velocity was significantly (p<0.05) less
      during deep water (upward mean (SD): 29.7 (14.0) cm x s(-1); downward: 31.1
      (17.0) cm x s(-1)) compared to treadmill running (upward mean (SD): 81.4 (21.7)
      cm x s(-1); downward: 100.0 (25.0) cm x s(-1)). CONCLUSION: Deep water running
      was perceived as a more strenuous but comfortable exercise mode for women with
      large breasts. Increased comfort was attributed to reduced vertical breast
      velocity rather than reduced vertical breast displacement.

PMID- 17535855
TI  - Measurement of human mixed muscle protein fractional synthesis rate depends on
      the choice of amino acid tracer.
AB  - The goal of this study was to discover whether using different tracers affects
      the measured rate of muscle protein synthesis in human muscle. We therefore
      measured the mixed muscle protein fractional synthesis rate (FSR) in the
      quadriceps of older adults during basal, postabsorptive conditions and mixed meal
      feeding (70 mg protein x kg fat-free mass(-1) x h(-1) x 2.5 h) by simultaneous
      intravenous infusions of [5,5,5-(2)H(3)]leucine and either [ring
      (13)C(6)]phenylalanine or [ring-(2)H(5)]phenylalanine and analysis of muscle
      tissue samples by gas chromatography-mass spectrometry. Both the basal FSR and
      the FSR during feeding were approximately 20% greater (P < 0.001) when calculated
      from the leucine labeling in muscle tissue fluid and proteins (fasted: 0.063 +/-
      0.005%/h; fed: 0.080 +/- 0.007%/h) than when calculated from the phenylalanine
      enrichment data (0.051 +/- 0.004 and 0.066 +/- 0.005%/h, respectively). The
      feeding-induced increase in the FSR ( approximately 20%; P = 0.011) was not
      different with leucine and phenylalanine tracers (P = 0.69). Furthermore, the
      difference between the leucine- and phenylalanine-derived FSRs was independent of
      the phenylalanine isotopomer used (P = 0.92). We conclude that when using stable
      isotope-labeled tracers and the classic precursor product model to measure the
      rate of muscle protein synthesis, absolute rates of muscle protein FSR differ
      significantly depending on the tracer amino acid used; however, the anabolic
      response to feeding is independent of the tracer used. Thus different precursor
      amino acid tracers cannot be used interchangeably for the evaluation of muscle
      protein synthesis, and data from studies using different tracer amino acids can
      be compared qualitatively but not quantitatively.

PMID- 17535856
TI  - The skeletal responsiveness to mechanical loading is enhanced in mice with a null
      mutation in estrogen receptor-beta.
AB  - Mechanical loading caused by physical activity can stimulate bone formation and
      strengthen the skeleton. Estrogen receptors (ERs) play some role in the signaling
      cascade that is initiated in bone cells after a mechanical load is applied. We
      hypothesized that one of the ERs, ER-beta, influences the responsiveness of bone
      to mechanical loads. To test our hypothesis, 16-wk-old male and female mice with
      null mutations in ER-beta (ER-beta(-/-)) had their right forelimbs subjected to
      short daily loading bouts. The loading technique used has been shown to increase
      bone formation in the ulna. Each loading bout consisted of 60 compressive loads
      within 30 s applied daily for 3 consecutive days. Bone formation was measured by
      first giving standard fluorochrome bone labels 1 and 6 days after loading and
      using quantitative histomorphometry to assess bone sections from the midshaft of
      the ulna. The left nonloaded ulna served as an internal control for the effects
      of loading. Mechanical loading increased bone formation rate at the periosteal
      bone surface of the mid-ulna in both ER-beta(-/-) and wild-type (WT) mice. The
      ulnar responsiveness to loading was similar in male ER-beta(-/-) vs. WT mice, but
      for female mice bone formation was stimulated more effectively in ER-beta(-/-)
      mice (P < 0.001). We conclude that estrogen signaling through ER-beta suppresses
      the mechanical loading response on the periosteal surface of long bones.

PMID- 17535857
TI  - Regulation of heme oxygenase-1 expression by demethoxy curcuminoids through Nrf2
      by a PI3-kinase/Akt-mediated pathway in mouse beta-cells.
AB  - Curcumin (diferuloylmethane), a component of turmeric, has been shown to have
      therapeutic properties. Induction of phase 2 detoxifying enzymes is a potential
      mechanism through which some of the actions of curcumin could proceed. Heme
      oxygenase-1 (HO-1), an antioxidant phase 2 enzyme, has been reported to have
      cytoprotective effects in pancreatic beta-cells. Curcumin on further purification
      yields demethoxy curcumin (DMC) and bisdemethoxy curcumin (BDMC). The objective
      of the present study was to determine the mechanism by which these purified
      curcuminoids induce HO-1 in MIN6 cells, a mouse beta-cell line. Demethoxy
      curcuminoids induced HO-1 promoter linked to the luciferase reporter gene more
      effectively than curcumin. The induction was dependent on the presence of
      antioxidant response element (ARE) sites containing enhancer regions (E1 and E2)
      in HO-1 promoter and nuclear translocation of nuclear factor-E2-related factor
      (Nrf2), the transcription factor that binds to ARE. Curcuminoids stimulated
      multiple signaling pathways that are known to induce HO-1. Inhibition of specific
      signaling pathways with pharmacological inhibitors and cotransfection experiments
      suggested the involvement of phosphotidylinositol 3-kinase and Akt. Real-time
      quantitative RT-PCR analysis showed significant elevation in the mRNA levels of
      HO-1 and two other phase 2 enzymes, the regulatory subunit of glutamyl cysteine
      ligase, which is needed for the synthesis of glutathione, and NAD(P)H:quinone
      oxidoreductase, which detoxifies quinones. DMC and BDMC induced the expression of
      HO-1 and translocated Nrf2 to nucleus in beta-cells of mouse islets. Our
      observations suggest that demethoxy curcuminoids could be used to induce a
      cellular defense mechanism in beta-cells under conditions of stress as seen in
      diabetes.

PMID- 17535859
TI  - Early hyponatraemia after pituitary surgery: cerebral salt-wasting syndrome.
AB  - Hyponatraemia is a common complication in patients undergoing neurosurgery. It
      can be caused either by the syndrome of inappropriate secretion of antidiuretic
      hormone or by the cerebral salt-wasting syndrome (CSWS). CSWS frequently occurs
      in patients suffering from subarachnoid haemorrhage and brain injury, but it is
      rare after pituitary tumour surgery. However, this diagnostic possibility should
      be considered as these disorders require specific treatment and have different
      prognoses. In this article, we present a case of acute and early hyponatraemia
      caused by CSWS after pituitary tumour surgery. We also revise the aetiology,
      mechanisms, differential diagnosis and treatment of hyponatraemia after pituitary
      surgery.

PMID- 17535860
TI  - Regressive liver adenomatosis following androgenic progestin therapy withdrawal:
      a case report with a 10-year follow-up and a molecular analysis.
AB  - OBJECTIVE: The relationship between sex hormones and hepatocellular adenoma
      development is well established. On the contrary, their contribution to liver
      adenomatosis (LA) development is still a debatable issue. Recently, inactivating
      mutations of hepatocyte nuclear factor-1alpha (HNF-1alpha) transcription factor
      gene or activating mutations of beta-catenin have been demonstrated in some liver
      adenomas, and a possible link between HNF-1alpha gene mutations and oral
      contraceptives has been suggested. Only two cases of regressive LA after hormone
      withdrawal therapy have been described so far but without any information
      concerning the molecular characteristics of the tumours. CASE: We report the case
      of a 48-year-old woman with LA, who had been taking an androgenic progestin
      therapy (lynestrenol) for 10 years. A major regression in the number and size of
      the lesions was observed 6 months after complete withdrawal of this therapy.
      METHODS: Hepatocellular adenomas were studied by immunohistochemistry for
      oestrogen, progesterone and androgen receptors (ER, PR and AR respectively), and
      for beta-catenin. Direct sequencing of the HNF-1alpha gene was also performed.
      RESULTS: For the first time, we demonstrate significant immunostaining of AR in
      the hepatocellular adenomas. This staining was negative in the partially
      regressive adenoma. Immunostainings for ER and PR were negative. HNF-1alpha and
      the beta-catenin pathways were not involved in tumour pathogenesis. CONCLUSIONS:
      Our case suggests a role of androgenic progestin therapy in some cases of LA.
      Hormone therapy withdrawal may induce a significant regression in lesions.

PMID- 17535861
TI  - Changes in expression of T-helper (Th) 1- and Th2-associated chemokine receptors
      on peripheral blood lymphocytes and plasma concentrations of their ligands,
      interferon-inducible protein-10 and thymus and activation-regulated chemokine,
      after antithyroid drug administration in hyperthyroid patients with Graves'
      disease.
AB  - OBJECTIVE: Although Graves' disease is considered an autoantibody-mediated, T
      helper 2 (Th2)-dominant disease, Th1-dominance may prevail in its initial phase.
      We longitudinally investigated Th1/Th2 balance in untreated hyperthyroid patients
      with Graves' disease after treatment of methimazole (MMI), an antithyroid drug.
      DESIGN: University clinic outpatients were studied prospectively. PATIENTS:
      Subjects included 23 untreated hyperthyroid patients with Graves' disease and 17
      age-matched control subjects. METHODS: Before and after treatment, we measured
      Th1- and Th2-associated chemokine receptors (CXCR)3 and CCR4, on peripheral blood
      lymphocytes using flow cytometry, as well as plasma concentrations of their
      ligands, interferon-inducible protein (IP)-10 and thymus and activation-regulated
      chemokine (TARC). RESULTS: The percentage of CXCR3-expressing cells among CD4+T
      lymphocytes and plasma IP-10 was significantly higher in hyperthyroid Graves'
      disease patients than in controls. At 12 and 24 weeks after initiation of MMI,
      percentage of CXCR3-expressing CD4+T lymphocytes had decreased significantly,
      while the percentage of CCR4-expressing CD4+T lymphocytes had increased
      significantly at 24 weeks. The CXCR3/CCR4 ratio had decreased significantly at 24
      weeks. Plasma concentrations of IP-10 had decreased significantly at 12 and 24
      weeks. Plasma concentrations of TARC also had decreased significantly at 24
      weeks. CONCLUSIONS: In hyperthyroid patients with Graves' disease in the active
      phase, Th1 cells rather than Th2 cells predominated among peripheral blood
      lymphocytes. After initiation of MMI, an ongoing transition from Th1 to Th2
      dominance occurred.

PMID- 17535862
TI  - Seasonality of month of birth of patients with Graves' and Hashimoto's diseases
      differ from that in the general population.
AB  - OBJECTIVE: We aimed to test the viral hypothesis in the pathogenesis of
      autoimmune thyroid disease (AITD). DESIGN: We determined the pattern of month of
      birth (MOB) distribution in patients with AITD and in the general population and
      searched for differences between them. METHODS: A total of 1023 patients were
      included in this study; 359 patients had Graves' hyperthyroidism (GrH) and 664
      had Hashimoto's hypothyroidism (HH). We divided the patients with HH into three
      subgroups according to their thyroid peroxidase (TPO) antibody titers at
      diagnosis: low levels (<500 IU/ml), high levels (500-1000 IU/ml), and extremely
      high levels (>1000 IU/ml). We used cosinor analysis to analyze the data. RESULTS:
      Overall, patients with GrH and HH had a different pattern of MOB distribution
      when compared with the general population and between groups. Furthermore, among
      both patients with GrH and HH, both genders had a different pattern of MOB
      distribution when compared with the general population and this pattern was also
      different between genders. Finally, only women with extremely high titers of TPO
      antibodies at diagnosis and men with low or extremely high TPO antibody levels
      showed rhythmicity in MOB, with a pattern of MOB distribution different from that
      in controls. CONCLUSIONS: The different MOB seasonality in both GrH and HH points
      towards a similar maybe even common etiology with type 1 diabetes mellitus and
      multiple sclerosis, namely a seasonal viral infection as the initial trigger in
      the perinatal period, the clinical disease resulting from further specific damage
      over time.

PMID- 17535863
TI  - Heterogeneity in responsiveness of perceived quality of life to body composition
      changes between adult- and childhood-onset Japanese hypopituitary adults with GH
      deficiency during GH replacement.
AB  - OBJECTIVE: To examine the responsiveness of quality of life (QoL) associated with
      changes in clinical indices relevant to GH deficiency (GHD) in Japanese
      hypopituitary adults. DESIGN AND METHODS: QoL was determined using the Short Form
      (SF)-36 in Japanese adults with adult-(AO; n = 27) or childhood- (CO; n = 37)
      onset GHD in a 24-week double-blind placebo-controlled study with a fixed GH
      dose, and a subsequent 48-week open-label extension study with GH doses
      individualized using serum IGF-I levels. RESULTS: Baseline QoL was significantly
      decreased from the Japanese national reference in both onset types, more so in AO
      patients. Throughout the study, AO patients showed a trend for an increase in
      physical functioning and general health (P = 0.0564 and 0.0999 respectively),
      whereas CO patients showed no changes in these domains. Fat mass changes
      negatively correlated with the changes in physical functioning and general health
      in AO patients (r = -0.42 and -0.64 respectively), but to a lesser degree in CO
      patients (r = -0.36 and -0.32 respectively). CO patients displayed significant
      decreases in social functioning (P = 0.0305) and mental health (P = 0.0442) and a
      decreasing trend in bodily pain (P = 0.0769), although no correlation between
      these decreases and any measured clinical index was observed, except between
      changes in bodily pain and IGF-I levels (r = -0.43). CONCLUSIONS: QoL impairment
      was evident in Japanese adults with GHD, particularly in AO patients. In AO
      patients, general health and physical functioning domains were responsive to fat
      mass changes during GH treatment; this association was not evident in CO
      patients. These relationships between QoL and body composition warrant
      verification.

PMID- 17535864
TI  - Pharmacokinetics and pharmacodynamics of GH: dependence on route and dosage of
      administration.
AB  - OBJECTIVE: Pharmacokinetic and pharmacodynamic data after recombinant human GH
      (rhGH) administration in adults are scarce, but necessary to optimize replacement
      therapy and to detect doping. We examined pharmacokinetics, pharmacodynamics, and
      20 kDa GH after injection of rhGH at different doses and routes of
      administration. DESIGN: Open-label crossover study with single boluses of rhGH.
      METHODS: Healthy trained subjects (10 males, 10 females) received bolus
      injections of rhGH on three occasions: 0.033 mg/kg s.c., 0.083 mg/kg s.c., and
      0.033 mg/kg i.m. Concentrations of 22 and 20 kDa GH, IGF-I, and IGF-binding
      proteins (IGFBP)-3 were measured repeatedly before and up to 36 h after
      injection. RESULTS: Serum GH maximal concentration (Cmax) and area under the time
      concentration curve (AUC) were higher after i.m. than s.c. administration of
      0.033 mg/kg (Cmax 35.5 and 12.0 microg/l; AUC 196.2 and 123.8). Cmax and AUC were
      higher in males than in females (P < 0.01) and pharmacodynamic changes were more
      pronounced. IGFBP-3 concentrations showed no dose dependency. In response to rhGH
      administration, 20 kDa GH decreased in females and remained suppressed for 14-18
      h (low dose) and 30 h (high dose). In males, 20 kDa GH was undetectable at
      baseline and throughout the study. CONCLUSIONS: After rhGH administration,
      pharmacokinetic parameters are mainly influenced by route of administration,
      whereas pharmacodynamic variables and 20 kDa GH concentrations are determined
      mainly by gender. These differences need to be considered for therapeutic use and
      for detection of rhGH doping.

PMID- 17535865
TI  - Superiority of skinfold measurements and waist over waist-to-hip ratio for
      determination of body fat distribution in a population-based cohort of Caucasian
      Dutch adults.
AB  - OBJECTIVE: To determine which anthropometric measurement is the most reliable
      alternative for fat distribution as measured by dual-energy X-ray absorptiometry
      (DXA). DESIGN: Population-based survey carried out in Amsterdam, The Netherlands.
      SUBJECTS AND METHODS: A total of 376 individuals (200 women) with a mean age of
      36.5 years and mean body mass index (BMI) of 24.0 (+/-3.1) kg/m2 underwent
      various anthropometric and DXA measurements of central (CFM) and peripheral fat
      mass (PFM). Furthermore, for the assessment of apple-shaped body composition, CFM
      to-PFM ratio was calculated. Anthropometric measurements were waist and hip
      circumference, waist-to-hip ratio (WHR), BMI, waist/length and the skinfold
      thickness of biceps, triceps, suprailiacal (SI), subscapular (SS) and upper leg.
      We determined whether equations of combined anthropometrics were even more
      reliable for the assessment of fat mass. RESULTS: In both women and men, reliable
      alternatives for CFM are central skinfolds and waist (Pearson's correlation (r)
      >or= 0.8). Peripheral skinfolds are the best predictors of PFM (r >or= 0.8). In
      contrast, WHR correlated only marginally with any of the DXA measurements.
      Equations based on several anthropometric variables correlate with CFM even
      better (R2 >or= 0.8). CFM-to-PFM ratio has the highest correlation with the ratio
      (SS+SI)/BMI in women (r = 0.66) and waist/length in men (r = 0.71). Equations are
      reasonable alternatives of CFM-to-PFM ratio (R2 >or= 0.5). CONCLUSION: Waist and
      skinfolds are reliable alternatives for the measurement of body fat mass in a
      cohort of Caucasian adults. WHR is not appropriate for the measurement of fat
      distribution.

PMID- 17535866
TI  - Co-localisation of the Kir6.2/SUR1 channel complex with glucagon-like peptide-1
      and glucose-dependent insulinotrophic polypeptide expression in human ileal cells
      and implications for glycaemic control in new onset type 1 diabetes.
AB  - OBJECTIVE: The ATP-dependent K+-channel (K(ATP)) is critical for glucose sensing
      and normal glucagon and insulin secretion from pancreatic endocrine alpha- and
      beta-cells. Gastrointestinal endocrine L- and K-cells are also glucose-sensing
      cells secreting glucagon-like peptide-1 (GLP-1) and glucose-dependent
      insulinotrophic polypeptide (GIP) respectively. The aims of this study were to 1)
      investigate the expression and co-localisation of the K(ATP) channel subunits,
      Kir6.2 and SUR1, in human L- and K-cells and 2) investigate if a common
      hyperactive variant of the Kir6.2 subunit, Glu23Lys, exerts a functional impact
      on glucose-sensing tissues in vivo that may affect the overall glycaemic control
      in children with new-onset type 1 diabetes. DESIGN AND METHODS: Western blot and
      immunohistochemical analyses were performed for expression and co-localisation
      studies. Meal-stimulated C-peptide test was carried out in 257 children at 1, 6
      and 12 months after diagnosis. Genotyping for the Glu23Lys variant was by PCR
      restriction fragment length polymorphism. RESULTS: Kir6.2 and SUR1 co-localise
      with GLP-1 in L-cells and with GIP in K-cells in human ileum tissue. Children
      with type 1 diabetes carrying the hyperactive Glu23Lys variant had higher HbA1C
      at diagnosis (coefficient = 0.61%, P = 0.02) and 1 month after initial insulin
      therapy (coefficient = 0.30%, P = 0.05), but later disappeared. However, when
      adjusting HbA1C for the given dose of exogenous insulin, the dose-adjusted HbA1C
      remained higher throughout the 12 month study period (coefficient = 0.42%, P =
      0.03). CONCLUSIONS: Kir6.2 and SUR1 co-localise in the gastrointestinal endocrine
      L- and K-cells. The hyperactive Glu23Lys variant of the K(ATP) channel subunit
      Kir6.2 may cause defective glucose sensing in several tissues and impaired
      glycaemic control in children with type 1 diabetes.

PMID- 17535867
TI  - Changes in calf muscle elasticity in hypogonadal males before and after
      testosterone substitution as monitored by magnetic resonance elastography.
AB  - PURPOSE: We sought to determine whether differences in muscle elasticity between
      healthy age-related controls and patients with hypogonadism could be measured by
      a new, non-invasive method termed magnetic resonance elastography (MRE).
      MATERIALS AND METHODS: Twelve hypogonadal (21-68 years) and twenty-seven healthy
      age-related men (20-76 years) were examined. In the hypogonadism group, serum
      testosterone levels were compared and MRE was conducted prior to and after 6
      months of therapy in 6 of the 12 patients. MRE was performed by mechanically
      exciting the soleus muscle that was used because of its uniformly distributed
      muscle fibers, size, and accessibility, with a custom designed piezoelectric
      actuator using a modified phase-contrast sequence. For mechanical excitation the
      actuator lever was placed on the anterior surface of the calf. The subjects had
      to maintain a force of 0-20% of their maximum voluntary contraction against a
      home-built footplate that was mounted on the MR table. All images were phase
      unwrapped and reconstructed into shear modulus elastograms using the local
      frequency estimation technique. RESULTS: Testosterone levels were significantly
      higher after 6 months of treatment. A statistical difference in the shear modulus
      was observed prior to and after 6 months of testosterone therapy and was nearly
      the same as in the healthy age-related control group. CONCLUSION: MRE seems to be
      a promising technique for the evaluation of therapeutic effects in patients with
      hypogonadism and possibly in other diseases with muscular effects.

PMID- 17535868
TI  - Quantitative liver functions in Turner syndrome with and without hormone
      replacement therapy.
AB  - BACKGROUND: Studies have documented elevated levels of liver enzymes in many
      females with Turner syndrome (TS). Histology has shown a range of changes.
      Treatment with female hormone replacement therapy (HRT) reduces liver enzymes.
      AIM: To study quantitative liver functions in TS in detail with and without HRT.
      DESIGN: Randomized crossover study with active treatment (HRT in TS and P-pill in
      controls) or no treatment. SUBJECTS: Women with TS (n = 8, age 29.7 +/- 5.6 (mean
      +/- s.d.) years), verified by karyotype, and age-matched controls (C; n = 8, age
      27.3 +/- 4.9 years). METHODS: We determined liver enzymes in blood, used the
      galactose elimination capacity to assess hepatocyte cytosol activity, plasma
      clearance of indocyanine green to assess excretory function, antipyrine clearance
      to estimate microsomal activity, and the functional hepatic nitrogen clearance
      (FHNC) to assess mitochondrial-cytosolic metabolic capacity for conversion of
      amino-nitrogen. RESULTS: Liver enzymes were elevated in untreated TS and reduced
      by HRT. The hepatic capacities for conversion of galactose, indocyanine green,
      and antipyrine were normal and did not change by HRT. The FHNC was marginally
      reduced (untreated TS vs C: 19.4 +/- 5.4 vs 25.2 +/- 7.3 L/h, P = 0.1). FHNC
      changed slightly with HRT in TS (19.4 +/- 5.4 vs 24.4 +/- 10.2 L/h, P = 0.2).
      CONCLUSIONS: The elevations of liver enzymes in untreated TS are readily
      suppressed by HRT. Quantitative liver functions in TS are comparable to controls
      and are not affected by HRT.

PMID- 17535869
TI  - Endogenous sex hormone levels in postmenopausal women undergoing carotid artery
      endarterectomy.
AB  - OBJECTIVE: To study the endogenous sex hormone levels in natural postmenopausal
      women and their association with the presence of internal carotid artery (ICA)
      atherosclerosis. DESIGN: Case-control study METHODS: We compared 56 patients with
      severe ICA atherosclerosis referred for carotid artery endarterectomy (CEA) with
      56 age-matched control subjects free of severe atherosclerotic disease. The
      presence of atherosclerosis was determined by high-resolution B-mode ultrasound.
      Metabolic parameters and sex hormones were measured or calculated: total
      cholesterol, high-density lipoprotein, low-density lipoprotein, triglycerides,
      glucose, insulin, quantitative insulin sensitivity check index, insulin
      resistance index, IGF-I, DHEA, DHEA sulfate (DHEA-S), free testosterone, total
      testosterone, estrone, estradiol, androstenedione, and sex hormone-binding
      globulin. RESULTS: The cases had statistically significant lower levels of both
      total testosterone (0.23 +/- 0.12 vs 0.31 +/- 0.20 microg/l, P = 0.043) and free
      testosterone (3.42 +/- 1.94 vs 4.59 +/- 2.97 ng/l, P = 0.009) and significantly
      lower levels of androstenedione (625.3 +/- 168.7 vs 697.0 +/- 211.9 ng/l, P =
      0.017) when compared with controls. Multivariate linear regression analysis,
      adjusted for traditional cardiovascular risk factors, baseline and physiologic
      characteristics, showed a significant inverse relationship between both serum
      free testosterone (beta = -0.234, P = 0.028) and androstenedione (beta = -0.241,
      P = 0.028) levels with the presence of severe atherosclerosis of ICA.
      CONCLUSIONS: The study provides evidence of a positive association between low
      serum androgen levels and severe ICA atherosclerosis in postmenopausal women. It
      suggests that higher, but physiological, levels of androgens in postmenopausal
      women have a protective role in the development of atherosclerosis of ICA.

PMID- 17535870
TI  - Effect of amiodarone and dronedarone administration in rats on thyroid hormone
      dependent gene expression in different cardiac components.
AB  - OBJECTIVE: In view of their different actions on thyroid hormone receptor (TR)
      isoforms we set out to investigate whether amiodarone (AM) and dronedarone (Dron)
      have different and/or component-specific effects on cardiac gene expression.
      DESIGN: Rats were treated with AM or Dron and the expression of TRalpha 1,
      TRalpha 2, TRbeta 1 and several tri-iodothyronine (T3)-regulated genes was
      studied in different parts of the heart, namely the right atrium (RA), left
      ventricular wall (LVW) and apex. METHODS: Rats were treated for 14 days with 100
      mg/kg body weight AM or Dron. The expression of TRalpha 1, TRalpha 2, TRbeta 1
      and T3-regulated genes was studied using real-time PCR and non-radioactive in
      situ hybridisation. RESULTS: AM and Dron affected TR expression in the RA
      similarly by decreasing TRalpha 1 and beta 1 expression by about 50%. In the LVW,
      AM and Dron decreased TRbeta 1 and, interestingly, AM increased TRalpha 1. In the
      apex, AM also increased TRalpha 2. The changes seen in T3-dependent gene
      expression are reminiscent of foetal reprogramming. CONCLUSION: Taken together,
      our results indicate that AM and Dron have similar effects on the expression of
      TR isoforms in the RA, which could partly contribute to their ability to decrease
      heart rate. On the other hand, the more profound effect of AM appears on TR- and
      T3-dependent gene expression in the left ventricle suggests foetal reprogramming.

PMID- 17535871
TI  - Critical role of toll-like receptors and nucleotide oligomerisation domain in the
      regulation of health and disease.
AB  - Pathogens are sensed by pattern recognition receptors (PRRs), which are germ line
      encoded receptors, including transmembrane Toll-like receptors (TLRs) and
      cytosolic nucleotide oligomerisation domain (NOD) proteins, containing leucine
      rich repeats (NLRs). Activation of PRRs by specific pathogen-associated molecular
      patterns (PAMPs) results in genomic responses in host cells involving activation
      transcription factors and the induction of genes. There are now at least 10 TLRs
      in humans and 13 in mice, and 2 NLRs (NOD1 and NOD2). TLR signalling is via
      interactions with adaptor proteins including MyD88 and toll-receptor associated
      activator of interferon (TRIF). NOD signalling is via the inflammasome and
      involves activation of Rip-like interactive clarp kinase (RICK). Bacterial
      lipopolysaccharide (LPS) from Gram-negative bacteria is the best-studied PAMP and
      is activated by or 'sensed' by TLR4. Lipoteichoic acid (LTA) from Gram-positive
      bacteria is sensed by TLR2. TLR4 and TLR2 have different signalling cascades,
      although activation of either results in symptoms of sepsis and shock. This
      review describes the rapidly expanding field of pathogen-sensing receptors and
      uses LPS and LTA as examples of how these pathways parallel and diverge from each
      other. The role of pathogen-sensing pathways in disease is also discussed.

PMID- 17535872
TI  - Expression of extracellular matrix proteins and integrins in rat adrenal gland:
      importance for ACTH-associated functions.
AB  - The expression of main extracellular matrix (ECM) and their integrins were
      studied in the adult rat adrenal gland. Collagen I, IV (CI, CIV), laminin (LN)
      and fibronectin (FN) expression was observed surrounding each glomerulosa cell
      and as long fibrils between the cords of fasciculata cells. In the medulla, FN
      was present around chromaffin cells or bordering blood vessels. Integrin alpha2,
      alpha3 and alpha5 were present mainly in the cortex, while alpha1 was present in
      the medulla. In culture, all ECM favoured proliferation of both glomerulosa and
      fasciculata cells, while protein synthesis was lower on FN and LN in glomerulosa
      cells. CIV promoted ACTH-induced proliferation whereas FN favoured ACTH-induced
      protein synthesis in glomerulosa cells. Except for LN, ECM increased expression
      of 3beta-hydroxysteroid dehydrogenase and enhanced basal aldosterone, although
      corticosterone secretion was only enhanced by CI and CIV. In fasciculata cells,
      the potency of ACTH-induced cAMP production was lower on ECM, compared with
      plastic. Moreover, ACTH, but not ECM, activated mitogenic-activated protein
      kinase p38 and stress-activated protein kinases. Glomerulosa and fasciculata
      cells grown on CI and CIV had a polygonal morphology, while cells grown on LN
      appeared as clusters of small rounded cells. On FN, the glomerulosa cells
      exhibited polygonal morphology while fasciculata cells appeared as clusters of
      small rounded cells. Together, these results indicate that ECM modulates basal
      and ACTH-induced cell functions, with FN, CI and CIV specifically favouring
      steroid secretion, as opposed to LN which inhibits secretion while promoting
      proliferation.

PMID- 17535873
TI  - Corticotropin-releasing factor (CRF) and CRF-binding protein expression in and
      release from the head kidney of common carp: evolutionary conservation of the
      adrenal CRF system.
AB  - Corticotropin-releasing factor (CRF) plays a central role in the regulation of
      the stress axis. In mammals, CRF as well as its receptors and its CRF-binding
      protein (CRF-BP) are expressed in a variety of organs and tissues outside the
      central nervous system. One of these extrahypothalamic sites is the adrenal
      gland, where the paracrine actions of adrenal CRF influence cortical
      steroidogenesis and adrenal blood flow. Although the central role of CRF
      signaling in the initiation and regulation of the stress response has now been
      established throughout vertebrates, information about the possible peripheral
      presence of CRF in earlier vertebrate lineages is scant. We established the
      expression of CRF, CRF-BP, and the CRF receptor 1 in a panel of peripheral organs
      of common carp (Cyprinus carpio). Out of all the peripheral organs tested, CRF
      and CRF-BP are most abundantly expressed in the carp head kidney, the fish
      equivalent of the mammalian adrenal gland. This expression localizes to
      chromaffin cells. Furthermore, detectable quantities of CRF are released from the
      intact head kidney following in vitro stimulation with 8-bromo-cAMP in a
      superfusion setup. The presence of CRF and CRF-BP within the chromaffin
      compartment of the head kidney suggests that a pathway homologous to the
      mammalian intra-adrenal CRF system is present in the head kidney of fish. It
      follows that such a system to locally fine-tune the outcome of the centrally
      initiated stress response has been an integral part of the vertebrate endocrine
      system since the common ancestor of teleostean fishes and mammals.

PMID- 17535874
TI  - Liver-derived IGF-I regulates kidney size, sodium reabsorption, and renal IGF-II
      expression.
AB  - The GH/-IGF-I axis is important for kidney size and function and may also be
      involved in the development of renal failure. In this study, the role of liver
      derived endocrine IGF-I for kidney size and function was investigated in mice
      with adult liver-specific IGF-I inactivation (LI-IGF-I(-/-) mice). These mice
      have an 80-85% reduction of serum IGF-I level and compensatory increased GH
      secretion. Seven-month-old as well as 24-month-old LI-IGF-I(-/-) mice had
      decreased kidney weight. Glomerular filtration rate, assessed using creatinine
      clearance as well as creatinine clearance corrected for body weight, was
      unchanged. The 24-h urine excretion of sodium and potassium was increased in the
      LI-IGF-I(-/-) mice. In the 24-month-old mice, there was no between-group
      difference in kidney morphology. Microarray and real-time PCR (RT-PCR) analyses
      showed a high renal expression of IGF-II in the control mice, whereas in the LI
      IGF-I(-/-) mice, there was a tissue-specific decrease in the renal IGF-II mRNA
      levels (-79%, P < 0.001 vs controls using RT-PCR). In conclusion, deficiency of
      circulating liver-derived IGF-I in mice results, despite an increase in GH
      secretion, in a global symmetrical decrease in kidney size, increased urinary
      sodium and potassium excretion, and a clear down regulation of renal IGF-II
      expression. However, the LI-IGF-I(-/-) mice did not develop kidney failure or
      nephrosclerosis. One may speculate that liver-derived endocrine IGF-I induces
      renal IGF-II expression, resulting in symmetrical renal growth.

PMID- 17535875
TI  - Regulation of glucokinase in pancreatic islets by prolactin: a mechanism for
      increasing glucose-stimulated insulin secretion during pregnancy.
AB  - Glucokinase activity is increased in pancreatic islets during pregnancy and in
      vitro by prolactin (PRL). The underlying mechanisms that lead to increased
      glucokinase have not been resolved. Since glucose itself regulates glucokinase
      activity in beta-cells, it was unclear whether the lactogen effects are direct or
      occur through changes in glucose metabolism. To clarify the roles of glucose
      metabolism in this process, we examined the interactions between glucose and PRL
      on glucose metabolism, insulin secretion, and glucokinase expression in insulin 1
      (INS-1) cells and rat islets. Although the PRL-induced changes were more
      pronounced after culture at higher glucose concentrations, an increase in glucose
      metabolism, insulin secretion, and glucokinase expression occurred even in the
      absence of glucose. The presence of comparable levels of insulin secretion at
      similar rates of glucose metabolism from both control and PRL-treated INS-1 cells
      suggests the PRL-induced increase in glucose metabolism is responsible for the
      increase in insulin secretion. Similarly, increases in other known PRL responsive
      genes (e.g. the PRL receptor, glucose transporter-2, and insulin) were also
      detected after culture without glucose. We show that the upstream glucokinase
      promoter contains multiple STAT5 binding sequences with increased binding in
      response to PRL. Corresponding increases in glucokinase mRNA and protein
      synthesis were also detected. This suggests the PRL-induced increase in
      glucokinase mRNA and its translation are sufficient to account for the elevated
      glucokinase activity in beta-cells with lactogens. Importantly, the increase in
      islet glucokinase observed with PRL is in line with that observed in islets
      during pregnancy.

PMID- 17535876
TI  - Endothelin-2 induces oviductal contraction via endothelin receptor subtype A in
      rats.
AB  - Proper function of the oviduct is critical to reproductive success with regulated
      contraction and relaxation facilitating transportation of the germ cells to the
      site of fertilization. Endothelin-2 (EDN2) is a potent vasoconstrictor produced
      by granulosa cells of the preovulatory follicle at the time of ovulation;
      however, whether this gonadotropin surge-induced peptide played a role in
      facilitating germ cell transportation by inducing oviductal contraction was
      unknown. The objectives of these experiments were (1) to determine whether the
      endothelin receptor system was present in the oviduct, (2) to test the hypothesis
      that EDN2 induces oviductal contraction via a specific endothelin receptor
      subtype, (3) to determine, as a possible alternate source of the ligand, whether
      mRNA for EDN2 was expressed in cumulus-oocyte complexes (COCs) within the
      oviduct, and (4) to determine whether EDN2 could overcome prostaglandin E(2)
      (PGE(2))-induced oviductal relaxation. Microarray and real-time PCR analysis
      indicated that mRNA for both the endothelin receptor subtypes (ET(A) and ET(B))
      was present in the oviduct, whereas immunohistochemical examination revealed that
      ET(A) protein was the dominant isoform, present in the luminal epithelial cells
      of the oviduct. Real-time PCR analysis demonstrated that mRNA for EDN2 was
      expressed in COCs after ovulation. Isometric tension analysis indicated that EDN2
      was a potent oviductal constrictor and that the contractile effect of EDN2 was
      mediated by the ET(A) and not the ET(B) receptor subtype. The oviductal
      contraction induced by EDN2 also reversed oviductal relaxation induced by PGE(2).
      In summary, ET(A) receptor-specific EDN2-induced contraction as a facilitator of
      oviductal function suggests a novel pathway involved in germ cell transport and
      hence mammalian fertility.

PMID- 17535877
TI  - Extracellular ATP activates nuclear translocation of ERK1/2 leading to the
      induction of matrix metalloproteinases expression in human endometrial stromal
      cells.
AB  - ATP has been shown to activate the mitogen-activated protein kinase (MAPK)
      signaling pathway in various systems. However, little is known about the
      signaling events and the effects in human endometrial stromal cells (hESCs). The
      present study examined the effect of ATP on activating MAPKs and its subsequent
      events in hESCs. This study demonstrated the expression of the P(2U)/P2Y(2)
      receptor in hESCs by reverse transcription-PCR (RT-PCR). A PCR product with a
      sequence identical to the reported 599 bp P(2U)/P2Y(2) receptor cDNA was
      obtained. Western blot analysis, using a monoclonal antibody against the
      phosphorylated forms of ERK1/2, demonstrated that ATP activated MAPK in a dose-
      and time-dependent manner. Confocal microscopy showed an evident nuclear
      translocation of phosphorylated ERKs after 10 microM ATP treatment, but this
      effect was blocked by PD98059. To study the gene(s) induced by exogenous ATP,
      mRNA was extracted from hESCs in the presence or absence of 10 microM ATP. The
      gene array for 96 genes associated with members of human matrix
      metalloproteinases (MMPs) and adhesion molecules revealed that the expression of
      MMP-2, -3, -10, and -24 genes was increased and the effect was attenuated by
      PD98059. Furthermore the effects of ATP on the expression of MMP genes were
      confirmed by semiquantitative RT-PCR. To our knowledge, this is the first
      demonstration of the ATP-induced nuclear translocation of phospho-ERK1/2 that
      mediates MMPs gene expression in human endometrial cells. These results support
      the notion that the ERK1/2 signaling pathway is involved in mediating ATP actions
      in the human reproductive system.

PMID- 17535878
TI  - Effects of maternal nuclear genome on the timing of puberty in mice offspring.
AB  - The timing of puberty is a complex trait which is regulated by environmental and
      genetic factors, but the detailed regulatory mechanism remains elusive. Maternal
      nutrition administration during late gestation in rats revealed that the time of
      onset of puberty in daughter rats was influenced by the mother's nutritional and
      physiological status during the embryonic development period. In this study, the
      potential effects of the maternal nuclear genome on the timing of puberty of
      offspring were investigated. Two inbred strains of mice (C3H/HeJ (C3H) and
      C57BL/6J (B6)) were used to set up two pedigrees (direct and reciprocal crosses),
      and the timing of puberty in all these mice (parent, F1 and F2) was recorded (the
      females were assessed by vaginal opening (VO) and the males by balano preputial
      separation (BPS)). The results from data of 822 mice showed that: 1) in female
      mice, the heritability of the timing of puberty in direct and reciprocal crosses
      is 68.51% and 63.97% respectively; 2) in female mice, a significant difference in
      the timing of puberty is observed between B6 and C3H (P = 3.7 x 10(-13)) mice as
      well as between direct and reciprocal F1 hybrids (P = 5.4 x 10(-3)), but not
      between direct and reciprocal F2 hybrids (P = 0.0941); 3) in male mice, direct
      and reciprocal F1 hybrids differ significantly from each other in the timing of
      BPS (P = 2.7 x 10(-7)), while such differences vanish in their male progenitor
      and progeny. The significant discrepancy between direct and reciprocal crosses in
      F1 but not in either cross of F2 hybrids reveals that the maternal nuclear genome
      has effects on the timing of puberty in mice progeny, probably through imprinting
      genes or the genes associated with intra-uterine physiological status.

PMID- 17535879
TI  - The disruption of circadian clockwork in differentiating cells from rat
      reproductive tissues as identified by in vitro real-time monitoring system.
AB  - The circadian clock, regulating hormonal secretion and metabolisms in accordance
      with the environmental light-dark cycle, resides in almost all peripheral tissues
      as well as in the superchiasmatic nucleus. Clock gene expression has been found
      to be noncyclic during spermatogenesis and the differentiation of thymocytes.
      However, currently little is known about how cell differentiation could affect
      circadian clockwork. We performed this study using the in vitro real-time
      oscillation monitoring system to examine the clockwork in several types of
      differentiating cells originated from reproductive tissues of transgenic rats
      (constructed with Period gene 2 (Per2) promoter-destabilized luciferase reporter
      gene). After treatment with dexamethasone (DXM), persistent oscillation of Per2
      expression was observed in both gonadotropin-induced and pregnant ovarian luteal
      cells, proliferative uterine stromal cells (USCs), and nondifferentiating
      testicular interstitial cells, with a cyclic period of ~24 h. In contrast to
      these cell types, only one cycle of oscillation was sustained in granulosa cells
      undergoing differentiation. Additionally, Per2 oscillation was irregular in USCs
      undergoing decidualization induced by medroxyprogesterone acetate plus N6, 2-O
      dibutyryl adenosine 3':5'-cyclic monophosphate. Furthermore, no oscillation of
      Per2 expression was evoked by DXM in Leydig cells and thymocytes. In conclusion,
      the present study characterized the oscillation of Per2 gene expression in
      several types of ovarian, uterine, and testicular cells, and it is strongly
      suggested that circadian clockwork is affected during cellular differentiation.

PMID- 17535880
TI  - Estrogen receptor {beta}1 exerts antitumoral effects on SK-OV-3 ovarian cancer
      cells.
AB  - Estrogen receptor (ER) beta1 and its splice variants are expressed both in ovary
      and ovarian cancer. We studied the role of ERbeta1 and two of its splice variants
      in regulation of gene expression, cellular proliferation, apoptosis, and
      migration of an ovarian cancer cell line. In this study, we transfected SK-OV-3
      ovarian cancer cells with vectors coding for ERbeta1 or its splice variants
      ERbeta-delta125 and ERbeta-delta1256, and tested their response to estrogen and
      tamoxifen in comparison with the untransfected cells. Heterologous expression of
      ERbeta1, but not of the exon-deleted ERbeta variants resulted in notably slower
      cell growth of SK-OV-3 ovarian cancer cells, an effect accompanied by more than
      tenfold increase of cyclin-dependent kinase inhibitor p21(WAF1) transcript levels
      and a significant reduction of cyclin A2 mRNA levels. SK-OV-3 cells stably
      overexpressing ERbeta1 ligand independently also exhibited an increased apoptosis
      rate and a significantly decreased motility, an effect accompanied by
      upregulation of fibulin 1c. Our data demonstrate that ERbeta1, but not the exon
      deleted isoforms tested exerts multiple antitumoral effects on SK-OV-3 ovarian
      cancer cells even in the absence of estradiol or functional ERalpha.

PMID- 17535881
TI  - Regulation of Dio2 gene expression by thyroid hormones in normal and type 1
      deiodinase-deficient C3H mice.
AB  - The C3H/HeJ mouse presents an inherited type 1 deiodinase (D1) deficiency that
      results in elevated serum thyroxine (T(4)), whereas TSH and tri-iodothyronine
      (T(3)) concentrations are normal when compared with those in the C57BL/6J strain.
      Here, we evaluated the expression of the type 2 (D2), the other T(4)-activating
      enzyme, in C3H mice. A comparative analysis revealed that D2 mRNA levels in C3H
      are similar to those in C57 animals. The D2 activity in C3H pituitary and brain
      are reduced when compared with those in the C57 strain (3.75 +/- 1.08 vs 5.78 +/-
      0.33 and 0.17 +/- 0.05 vs 0.26 +/- 0.07 fmol/min per mg protein respectively).
      However, no differences on D2 activity levels were observed in the brown adipose
      tissue (BAT) between both strains (0.34 +/- 0.06 vs 0.36 +/- 0.09 fmol/min per mg
      protein). Experiments using different T(4) doses showed that higher levels of
      serum T(4) than those of the C3H mouse are required to downregulate D2 activity
      in this tissue. T(3) administration to euthyroid mice resulted in a two- to four
      fold increase on D2 activity in BAT and brain of both strains, despite a marked
      decrease in BAT D2 transcripts and no changes in brain D2 mRNA levels. The
      increase in D2 activity was preceded by a decrease in serum T(4) levels, which
      appears to reduce D2 degradation. Indeed, administration of T(3) plus T(4)
      abolished the T(3)-induced D2 upregulation. In conclusion, our results
      demonstrated that D2 activity is mainly regulated at posttranslational level in a
      tissue-specific manner. These observations further characterize and provide
      insights into the complex and dual regulatory role of the iodothyronines in D2
      regulation.

PMID- 17535882
TI  - Functional characterization of human 1-acylglycerol-3-phosphate-O-acyltransferase
      isoform 9: cloning, tissue distribution, gene structure, and enzymatic activity.
AB  - Most cells synthesize their glycerophospholipids and triglycerides (TG) to
      maintain the cellular integrity and to provide energy for cellular functions. The
      phospholipids are synthesized de novo in cells through an evolutionary conserved
      process involving serial acylations of glycerol-3-phosphate. Several isoforms of
      the enzyme 1-acylglycerol-3-phosphate-O-acyltransferase (AGPAT) acylate
      lysophosphatidic acid at the sn-2 position to produce phosphatidic acid. We
      cloned a cDNA predicted to be an AGPAT isoform and designated it AGPAT9. The
      human AGPAT9 gene spans across 14 exons and encodes for a polypeptide of 534
      amino acids. AGPAT9 is highly expressed in the lung and spleen, followed by
      leukocyte, omental adipose tissue, and placenta. In the Chinese Hamster Ovary
      (CHO), cell lysates overexpressing AGPAT9, we observed AGPAT activity but not the
      lysophosphatidylcholine acyltransferase activity. When AGPAT9 is coexpressed with
      AGPAT1 in CHO cells, both the isoforms localize to the endoplasmic reticulum (ER)
      and occupy the same ER domain as AGPAT1. Despite substitution of asparagine with
      proline in the NHX(4)D motif and arginine with cysteine in the EGTR motif, AGPAT9
      retains AGPAT activity suggesting that residues asparagine and arginine in the
      NHX(4)D and EGTR motifs respectively are not essential for the enzymatic
      activity. Based on the X-ray crystallographic structure of a related
      acyltransferase, squash gpat, a model is proposed in which a hydrophobic pocket
      in AGPAT9 accommodates fatty acyl chains of both substrates in an orientation,
      whereas the HX(4)D motif participates in catalysis. Based on the activity and
      expression pattern of AGPAT9 in the lung and spleen, this novel isoform could be
      implicated in the biosynthesis of phospholipids and TG in these tissues.

PMID- 17535883
TI  - The vitamin D receptor and its ligand 1alpha,25-dihydroxyvitamin D3 in Atlantic
      salmon (Salmo salar).
AB  - Seaward migration of Salmo salar is preceded by preparatory physiological
      adaptations (parr-smolt transformation) to allow for a switch from freshwater
      (FW) to seawater (SW), which also means a switch in ambient calcium from
      hypocalcic (<1 mM Ca(2+)) to the plasma (~1.25 mM Ca(2+)) and to strongly
      hypercalcic (8-12 mM Ca(2+)). Uptake, storage (skeleton, scales) and excretion of
      calcium need careful regulation. In fish, the vitamin D endocrine system plays a
      rather enigmatic role in calcium physiology. Here, we give direct evidence for
      calcitriol involvement in SW migration. We report the full sequence of the
      nuclear vitamin D receptor (sVDR0) and two alternatively spliced variants
      resulting from intron retention (sVDR1 and sVDR2). In FW parr, SW adapting
      smolts, and in SW adults, plasma concentrations of 25(OH)D(3) and
      24,25(OH)(2)D(3) did not change significantly. Plasma calcitriol concentrations
      were lowest in FW parr, doubled during smoltification and remained elevated in SW
      adults. Increased calcitriol coincided with a twofold decrease in sVDR mRNA
      levels in gill, intestine, and kidney of FW smolts and SW adults, when compared
      with parr. Clearly, there was a negative feedback and dynamic response of the
      vitamin D endocrine system during parr-smolt transformation. The onset of these
      dynamic changes in FW parr warrants a further search for the endocrines that
      initiate these changes. We speculate that the vitamin D system plays a crucial
      role in calcium and phosphorus handling in Atlantic salmon.

PMID- 17535884
TI  - Parathyroid hormone-related protein and calcium regulation in vitamin D-deficient
      sea bream (Sparus auratus).
AB  - Gilthead sea bream (Sparus auratus L.) were fed a vitamin D-deficient diet for 22
      weeks. Growth rate, whole body mineral pools and calcium balance were determined.
      Plasma parathyroid hormone-related protein (PTHrP) and calcitriol levels were
      assessed. Expression of mRNA for pthrp and pth1r was quantified in gills and
      hypophysis. Fish on vitamin D-deficient diet (D- fish) showed reduced growth and
      lower calcium turnover (calcium influx, efflux and accumulation rates decreased)
      and unaltered plasma calcium levels. Plasma calcitriol levels became
      undetectable, PTHrP levels decreased in the D- fish. In controls, a significant
      increase in plasma PTHrP level over time was seen, i.e. it increased with body
      mass. Relationships were found between plasma PTHrP and the whole body pools of
      calcium, phosphorus and magnesium, indicative of a role for PTHrP in bone
      development. Expression of pthrp and pth1r mRNA was down-regulated in the
      hypophysis of D-fish, whereas in gill tissue, pthrp and pth1r mRNA were up
      regulated. We conclude that lower pthrp mRNA expression and plasma values in D-
      fish reflect lower turnover of PTHrP under conditions of hampered growth; up
      regulation of pthrp mRNA in gills indicate compensatory paracrine activity of
      PTHrP during calcitriol deficiency to guarantee well-regulated branchial calcium
      uptake. This is the first report to document a relation between PTHrP and
      calcitriol in fish.

PMID- 17535885
TI  - Expression of endocrine genes in zebrafish larvae in response to environmental
      salinity.
AB  - We tested the capability of the endocrine system in zebrafish to respond to
      environmental salinity challenges during larval stages. We reveal that the
      zebrafish larvae have a system in which several endocrine genes, including atrial
      natriuretic peptide (anp), renin, prolactin, growth hormone ( gh) and parathyroid
      hormone 1 (pth1), respond at the transcription level to changes in environmental
      salinity and that the responses are gene specific. Both anp and renin are
      upregulated in larvae raised in dilute freshwater medium but are downregulated in
      concentrated medium. On the other hand, expression of prolactin and gh is
      strongly enhanced in the dilute medium, but shows little or no change under
      higher salinity conditions. Interestingly, PTH1 expression depends on Ca(2+)
      concentration, as observed in mammals. Thus, taken together with the advantages
      of a model organism, including accessibility to genetic approaches, we propose
      that zebrafish larvae are useful for a comprehensive study of the regulatory
      mechanisms of the endocrine system in ionic and osmotic homeostasis.

PMID- 17535886
TI  - The effects of synthetic 19-norprogestins on osteoblastic cell function are
      mediated by their non-phenolic reduced metabolites.
AB  - The key role of estrogens on osteoblastic cell function is well documented;
      however, the role of progesterone (P) and synthetic progestins remains
      controversial. While several reports indicate that P has no significant effects
      on bone cells, a number of clinical studies have shown that 19-norprogestins
      restore postmenopausal bone loss. The mechanisms by which 19-norprogestins induce
      estrogen-like effects on bone cells are not fully understood. To assess whether
      the actions of 19-norprogestins on osteoblasts are mediated by their non-phenolic
      metabolites, we studied the effects of norethisterone (NET), levonorgestrel
      (LNG), and two of their A-ring reduced derivatives upon cell proliferation and
      differentiation in neonatal rat osteoblasts. Osteoblast function was assessed by
      determining cell DNA, cell-associated osteocalcin and calcium content, alkaline
      phosphatase activity, and mineral deposition. P failed to induce changes on
      osteoblasts, while NET and LNG exerted a number of actions. The most striking
      finding was that the 3beta,5alpha- and 3alpha,5alpha-tetrahydro derivatives of
      NET and LNG induced osteoblast proliferation and differentiation with higher
      potency than those exerted by their parent compounds, mimicking the effects of
      estradiol. Interestingly, osteoblast differentiation and mineral deposition
      induced by NET and LNG were abolished by finasteride, a 5alpha-reductases
      inhibitor, while the potent effect on osteoblast proliferation induced by
      progestin derivatives was abolished by a steroidal antiestrogen. Results
      demonstrate that A-ring reduced derivatives of NET and LNG exhibit intrinsic
      estrogen-like potency on rat osteoblasts, offering a plausible explanation for
      the mechanism of action of 19-norprogestins in bone restoration in postmenopausal
      women and providing new insights for hormone replacement therapy research.

PMID- 17535887
TI  - Identifying pattern-defined regulatory islands in mammalian genomes.
AB  - Identifying cis-regulatory regions in mammalian genomes is a key challenge toward
      understanding transcriptional regulation. However, identification and functional
      characterization of those regulatory elements governing differential gene
      expression has been hampered by the limited understanding of their organization
      and locations in genomes. We hypothesized that genes that are conserved across
      species will also display conservation at the level of their transcriptional
      regulation and that this will be reflected in the organization of cis-elements
      mediating this regulation. Using a computational approach, clusters of
      transcription factor binding sites that are absolutely conserved in order and in
      spacing across human, rat, and mouse genomes were identified. We term these
      regions pattern-defined regulatory islands (PRIs). We discovered that these
      sequences are frequently active sites of transcriptional regulation. These PRIs
      occur in approximately 1.1% of the half-billion base pairs covered in the search
      and are located mainly in noncoding regions of the genome. We show that the
      premise of PRIs can be used to identify previously known and novel cis-regulatory
      regions controlling genes regulated by myogenic differentiation. Thus, PRIs may
      represent a fundamental property of the architecture of cis-regulatory elements
      in mammalian genomes, and this feature can be exploited to pinpoint critical
      transcriptional regulatory elements governing cell type-specific gene expression.

PMID- 17535888
TI  - A simplified recipe for prions.

PMID- 17535889
TI  - Cooperative light-induced molecular movements of highly ordered azobenzene self
      assembled monolayers.
AB  - Photochromic systems can convert light energy into mechanical energy, thus they
      can be used as building blocks for the fabrication of prototypes of molecular
      devices that are based on the photomechanical effect. Hitherto a controlled
      photochromic switch on surfaces has been achieved either on isolated chromophores
      or within assemblies of randomly arranged molecules. Here we show by scanning
      tunneling microscopy imaging the photochemical switching of a new terminally
      thiolated azobiphenyl rigid rod molecule. Interestingly, the switching of entire
      molecular 2D crystalline domains is observed, which is ruled by the interactions
      between nearest neighbors. This observation of azobenzene-based systems
      displaying collective switching might be of interest for applications in high
      density data storage.

PMID- 17535890
TI  - Stepwise proteolysis liberates tau fragments that nucleate the Alzheimer-like
      aggregation of full-length tau in a neuronal cell model.
AB  - Tau is a highly soluble protein, yet it aggregates abnormally in Alzheimer's
      disease. Here, we address the question of proteolytic processing of tau and the
      nucleation of aggregates by tau fragments. We show in neuronal cell models that
      fragments of the repeat domain of tau containing mutations of FTDP17
      (frontotemporal dementia with parkinsonism linked to chromosome 17), produced by
      endogenous proteases, can induce the aggregation of full-length tau. Fragments
      are generated by successive cleavages, first N-terminally between K257 and S258,
      then C-terminally around residues 353-364; conversely, when the N-terminal
      cleavage is inhibited, no fragmentation and aggregation takes place. The C
      terminal truncation and the coaggregation of fragments with full-length tau
      depends on the propensity for beta-structure. The aggregation is modulated by
      phosphorylation but does not depend on it. Aggregation but not fragmentation as
      such is toxic to cells; conversely, toxicity can be prevented by inhibiting
      either aggregation or proteolysis. The results reveal a novel pathway of abnormal
      tau aggregation in neuronal cells.

PMID- 17535891
TI  - Lean gene and the clock machine.

PMID- 17535892
TI  - Lithocholic acid can carry out in vivo functions of vitamin D.
AB  - The physiological ligand for the vitamin D receptor (VDR) is 1,25
      dihydroxyvitamin D(3). Lithocholic acid (LCA), a bile acid implicated in the
      progression of colon cancer, was recently shown to bind to VDR with low affinity
      and increase expression of the xenobiotic enzymes of the CYP3A family. Thus, LCA
      can induce its own catabolism through the VDR. We have now found that LCA can
      substitute for vitamin D in the elevation of serum calcium in vitamin D-deficient
      rats. Further, LCA in the diet will also replace vitamin D in the mobilization of
      calcium from bone. Further, LCA induces CYP24-hydroxylase mRNA gene expression in
      the kidney of vitamin D-deficient rats. It is clear, therefore, that LCA can be
      absorbed into the circulation to bind to the VDR at extra-intestinal sites. These
      findings lend support for the idea that the VDR may have evolved from an original
      role in detoxification.

PMID- 17535894
TI  - Internal DNA pressure modifies stability of WT phage.
AB  - dsDNA in bacteriophages is highly stressed and exerts internal pressures of many
      atmospheres (1 atm = 101.3 kPa) on the capsid walls. We investigate the
      correlation between packaged DNA length in lambda phage (78-100% of WT DNA) and
      capsid strength by using an atomic force microscope indentation technique. We
      show that phages with WT DNA are twice as strong as shorter genome mutants, which
      behave like empty capsids, regardless of high internal pressure. Our analytical
      model of DNA-filled capsid deformation shows that, because of DNA-hydrating water
      molecules, an osmotic pressure exists inside capsids that increases exponentially
      when the packaged DNA density is close to WT phage. This osmotic pressure raises
      the WT capsid strength and is approximately equal to the maximum breaking force
      of empty shells. This result suggests that the strength of the shells limits the
      maximal packaged genome length. Moreover, it implies an evolutionary optimization
      of WT phages allowing them to survive greater external mechanical stresses in
      nature.

PMID- 17535893
TI  - [18F]MK-9470, a positron emission tomography (PET) tracer for in vivo human PET
      brain imaging of the cannabinoid-1 receptor.
AB  - [(18)F]MK-9470 is a selective, high-affinity, inverse agonist (human IC(50), 0.7
      nM) for the cannabinoid CB1 receptor (CB1R) that has been developed for use in
      human brain imaging. Autoradiographic studies in rhesus monkey brain showed that
      [(18)F]MK-9470 binding is aligned with the reported distribution of CB1 receptors
      with high specific binding in the cerebral cortex, cerebellum, caudate/putamen,
      globus pallidus, substantia nigra, and hippocampus. Positron emission tomography
      (PET) imaging studies in rhesus monkeys showed high brain uptake and a
      distribution pattern generally consistent with that seen in the autoradiographic
      studies. Uptake was blocked by pretreatment with a potent CB1 inverse agonist, MK
      0364. The ratio of total to nonspecific binding in putamen was 4-5:1, indicative
      of a strong specific signal that was confirmed to be reversible via displacement
      studies with MK-0364. Baseline PET imaging studies in human research subject
      demonstrated behavior of [(18)F]MK-9470 very similar to that seen in monkeys,
      with very good test-retest variability (7%). Proof of concept studies in healthy
      young male human subjects showed that MK-0364, given orally, produced a dose
      related reduction in [(18)F]MK-9470 binding reflecting CB1R receptor occupancy by
      the drug. Thus, [(18)F]MK-9470 has the potential to be a valuable, noninvasive
      research tool for the in vivo study of CB1R biology and pharmacology in a variety
      of neuropsychiatric disorders in humans. In addition, it allows demonstration of
      target engagement and noninvasive dose-occupancy studies to aid in dose selection
      for clinical trials of CB1R inverse agonists.

PMID- 17535895
TI  - Bisphosphonates target multiple sites in both cis- and trans-prenyltransferases.
AB  - Bisphosphonate drugs (e.g., Fosamax and Zometa) are thought to act primarily by
      inhibiting farnesyl diphosphate synthase (FPPS), resulting in decreased
      prenylation of small GTPases. Here, we show that some bisphosphonates can also
      inhibit geranylgeranyl diphosphate synthase (GGPPS), as well as undecaprenyl
      diphosphate synthase (UPPS), a cis-prenyltransferase of interest as a target for
      antibacterial therapy. Our results on GGPPS (10 structures) show that there are
      three bisphosphonate-binding sites, consisting of FPP or isopentenyl diphosphate
      substrate-binding sites together with a GGPP product- or inhibitor-binding site.
      In UPPS, there are a total of four binding sites (in five structures). These
      results are of general interest because they provide the first structures of
      GGPPS- and UPPS-inhibitor complexes, potentially important drug targets, in
      addition to revealing a remarkably broad spectrum of binding modes not seen in
      FPPS inhibition.

PMID- 17535896
TI  - Discovery of parasite virulence genes reveals a unique regulator of chromosome
      condensation 1 ortholog critical for efficient nuclear trafficking.
AB  - Eukaryotic parasites are a leading cause of morbidity and mortality worldwide,
      yet little is known about the genetic basis of their virulence. Here, we present
      a forward genetic screen to study pathogenesis in the protozoan parasite
      Toxoplasma gondii. By using modified signature-tagged mutagenesis, the growth of
      6,300 T. gondii insertional mutants was compared in cell culture and murine
      infection to identify genes required specifically in vivo. One of the 39
      avirulent mutants is disrupted in a divergent ortholog of the regulator of
      chromosome condensation 1 (RCC1), which is critical for nuclear trafficking in
      model systems. Although this RCC1 mutant grows similar to wild type in standard
      tissue culture conditions, it is growth-impaired under nutrient limitation.
      Genetic complementation of mutant parasites with the T. gondii RCC1 gene fully
      restores both virulence in mice and growth under low-nutrient conditions. Further
      analysis shows that there is a significant defect in nuclear trafficking in the
      RCC1 mutant. These findings suggest that the rate of nuclear transport is a
      critical factor affecting growth in low-nutrient conditions in vivo and in vitro.
      Additionally, we observed that although RCC1 proteins are highly conserved in
      organisms from humans to yeast, no protozoan parasite encodes a characteristic
      RCC1. This protein divergence may represent a unique mechanism of
      nucleocytoplasmic transport. This study illustrates the power of this forward
      genetics approach to identify atypical virulence mechanisms.

PMID- 17535897
TI  - Profile of Roy H. Doi.

PMID- 17535898
TI  - Docosahexaenoic acid alters bilayer elastic properties.
AB  - At low micromolar concentrations, polyunsaturated fatty acids (PUFAs) alter the
      function of many membrane proteins. PUFAs exert their effects on unrelated
      proteins at similar concentrations, suggesting a common mode of action. Because
      lipid bilayers serve as the common "solvent" for membrane proteins, the common
      mechanism could be that PUFAs adsorb to the bilayer/solution interface to promote
      a negative-going change in lipid intrinsic curvature and, like other reversibly
      adsorbing amphiphiles, increase bilayer elasticity. PUFA adsorption thus would
      alter the bilayer deformation energy associated with protein conformational
      changes involving the protein/bilayer boundary, which would alter protein
      function. To explore the feasibility of such a mechanism, we used gramicidin (gA)
      analogues of different lengths together with bilayers of different thicknesses to
      assess whether docosahexaenoic acid (DHA) could exert its effects through a
      bilayer-mediated mechanism. Indeed, DHA increases gA channel appearance rates and
      lifetimes and decreases the free energy of channel formation. The appearance rate
      and lifetime changes increase with increasing channel-bilayer hydrophobic
      mismatch and are not related to differing DHA bilayer absorption coefficients.
      DHA thus alters bilayer elastic properties, not just lipid intrinsic curvature;
      the elasticity changes are important for DHA's bilayer-modifying actions. Oleic
      acid (OA), which has little effect on membrane protein function, exerts no such
      effects despite OA's adsorption coefficient being an order of magnitude greater
      than DHA's. These results suggest that DHA (and other PUFAs) may modulate
      membrane protein function by bilayer-mediated mechanisms that do not involve
      specific protein binding but rather changes in bilayer material properties.

PMID- 17535899
TI  - Inhibition of ubiquitin-mediated degradation of MOAP-1 by apoptotic stimuli
      promotes Bax function in mitochondria.
AB  - The multidomain proapoptotic protein Bax of the Bcl-2 family is a central
      regulator for controlling the release of apoptogenic factors from mitochondria.
      Recent evidence suggests that the Bax-associating protein MOAP-1 may act as an
      effector for promoting Bax function in mitochondria. Here, we report that MOAP-1
      protein is rapidly up-regulated by multiple apoptotic stimuli in mammalian cells.
      MOAP-1 is a short-lived protein (t(1/2) approximately 25 min) that is
      constitutively degraded by the ubiquitin-proteasome system. Induction of MOAP-1
      by apoptotic stimuli ensues through inhibition of its polyubiquitination process.
      Elevation of MOAP-1 levels sensitizes cells to apoptotic stimuli and promotes
      recombinant Bax-mediated cytochrome c release from isolated mitochondria.
      Mitochondria depleted of short-lived proteins by cycloheximide (CHX) become
      resistant to Bax-mediated cytochrome c release. Remarkably, incubation of these
      mitochondria with in vitro-translated MOAP-1 effectively restores the cytochrome
      c releasing effect of recombinant Bax. We propose that apoptotic stimuli can
      facilitate the proapoptotic function of Bax in mitochondria through stabilization
      of MOAP-1.

PMID- 17535900
TI  - The induced prostaglandin E2 pathway is a key regulator of the respiratory
      response to infection and hypoxia in neonates.
AB  - Infection during the neonatal period commonly induces apnea episodes, and the
      proinflammatory cytokine IL-1beta may serve as a critical mediator between these
      events. To determine the mechanism by which IL-1beta depresses respiration, we
      examined a prostaglandin E(2) (PGE(2))-dependent pathway in newborn mice and
      human neonates. IL-1beta and transient anoxia rapidly induced brainstem-specific
      microsomal prostaglandin E synthase-1 (mPGES-1) activity in neonatal mice.
      Furthermore, IL-1beta reduced respiratory frequency during hyperoxia and
      depressed hypoxic gasping and autoresuscitation in mPGES-1 wild-type mice, but
      not in mPGES-1 knockout mice. In wild-type mice, PGE(2) induced apnea and
      irregular breathing patterns in vivo and inhibited brainstem respiratory rhythm
      generation in vitro. Mice lacking the EP3 receptor (EP3R) for PGE(2) exhibited
      fewer apneas and sustained brainstem respiratory activity, demonstrating that
      PGE(2) exerts its respiratory effects via EP3R. In human neonates, the infectious
      marker C-reactive protein was correlated with elevated PGE(2) in the
      cerebrospinal fluid, and elevated central PGE(2) was associated with an increased
      apnea frequency. We conclude that IL-1beta adversely affects breathing and its
      control by mPGES-1 activation and PGE(2) binding to brainstem EP3 receptors,
      resulting in increased apnea frequency and hypoxia-induced mortality.

PMID- 17535901
TI  - Protein structure determination from NMR chemical shifts.
AB  - NMR spectroscopy plays a major role in the determination of the structures and
      dynamics of proteins and other biological macromolecules. Chemical shifts are the
      most readily and accurately measurable NMR parameters, and they reflect with
      great specificity the conformations of native and nonnative states of proteins.
      We show, using 11 examples of proteins representative of the major structural
      classes and containing up to 123 residues, that it is possible to use chemical
      shifts as structural restraints in combination with a conventional molecular
      mechanics force field to determine the conformations of proteins at a resolution
      of 2 angstroms or better. This strategy should be widely applicable and, subject
      to further development, will enable quantitative structural analysis to be
      carried out to address a range of complex biological problems not accessible to
      current structural techniques.

PMID- 17535902
TI  - A unique T cell receptor discovered in marsupials.
AB  - T cells recognize antigens by using T cell receptors (TCRs) encoded by gene
      segments, called variable (V), diversity (D), and joining (J), that undergo
      somatic recombination to create diverse binding specificities. Four TCR chains
      (alpha, beta, gamma, and delta) have been identified to date, and, as T cells
      develop in the thymus, they express exclusively either an alphabetaTCR or a
      gammadeltaTCR heterodimer. Here, we show that marsupials have an additional TCR
      (TCRmu) that has V, D, and J that are either somatically recombined, as in
      conventional TCRs, or are already prejoined in the germ-line DNA in a manner
      consistent with their creation by retrotransposition. TCRmu does not have a known
      homolog in eutherian mammals but has features analogous to a recently described
      TCRdelta isoform in sharks. TCRmu is expressed in at least two mRNA isoforms that
      appear capable of encoding a full-length protein, both of which are transcribed
      in the thymus and spleen. One contains two variable domains: a somatically
      recombined V and a prejoined V. This appears to be the dominant isoform in
      peripheral lymphoid tissue. The other isoform contains only the prejoined V and
      is structurally more similar to conventional TCR chains, however invariant.
      Unlike other TCRs, TCRmu uses prejoined gene segments and is likely present in
      all marsupials. Its similarity to a TCR isoform in sharks suggests that it, or
      something similar, may be present in other vertebrate lineages and, therefore,
      may represent an ancient receptor system.

PMID- 17535903
TI  - Alarin is a vasoactive peptide.
AB  - Galanin-like peptide (GALP) is a hypothalamic neuropeptide belonging to the
      galanin family of peptides. The GALP gene is characterized by extensive
      differential splicing in a variety of murine tissues. One splice variant excludes
      exon 3 and results in a frame shift leading to a novel peptide sequence and a
      stop codon after 49 aa. In this peptide, which we termed alarin, the signal
      sequence of the GALP precursor peptide and the first 5 aa of the mature GALP are
      followed by 20 aa without homology to any other murine protein. Alarin mRNA was
      detected in murine brain, thymus, and skin. In accordance with its vascular
      localization, the peptide exhibited potent and dose-dependent vasoconstrictor and
      anti-edema activity in the cutaneous microvasculature, as was also observed with
      other members of the galanin peptide family. However, in contrast to galanin
      peptides in general, the physiological effects of alarin do not appear to be
      mediated via the known galanin receptors. Alarin adds another facet to the
      surprisingly high-functional redundancy of the galanin family of peptides.

PMID- 17535904
TI  - Receptor-mediated activation of nitric oxide synthesis by arginine in endothelial
      cells.
AB  - Arginine contains the guanidinium group and thus has structural similarity to
      ligands of imidazoline and alpha-2 adrenoceptors (alpha-2 AR). Therefore, we
      investigated the possibility that exogenous arginine may act as a ligand for
      these receptors in human umbilical vein endothelial cells and activate
      intracellular nitric oxide (NO) synthesis. Idazoxan, a mixed antagonist of
      imidazoline and alpha-2 adrenoceptors, partly inhibited L-arginine-initiated NO
      formation as measured by a Griess reaction. Rauwolscine, a highly specific
      antagonist of alpha-2 AR, at very low concentrations completely inhibited NO
      formation. Like L-arginine, agmatine (decarboxylated arginine) also activated NO
      synthesis, however, at much lower concentrations. We found that dexmedetomidine,
      a specific agonist of alpha-2 AR was very potent in activating cellular NO, thus
      indicating a possible role for alpha-2 AR in L-arginine-mediated NO synthesis. D
      arginine also activated NO production and could be inhibited by imidazoline and
      alpha-2 AR antagonists, thus indicating nonsubstrate actions of arginine.
      Pertussis toxin, an inhibitor of G proteins, attenuated L-arginine-mediated NO
      synthesis, thus indicating mediation via G proteins. L-type Ca(2+) channel
      blocker nifedipine and phospholipase C inhibitor U73122 inhibited NO formation
      and thus implicated participation of a second messenger pathway. Finally, in
      isolated rat gracilis vessels, rauwolscine completely inhibited the L-arginine
      initiated vessel relaxation. Taken together, these data provide evidence for
      binding of arginine to membrane receptor(s), leading to the activation of
      endothelial NO synthase (eNOS) NO production through a second messenger pathway.
      These findings provide a previously unrecognized mechanistic explanation for the
      beneficial effects of L-arginine in the cardiovascular system and thus provide
      new potential avenues for therapeutic development.

PMID- 17535905
TI  - Target mRNAs are repressed as efficiently by microRNA-binding sites in the 5' UTR
      as in the 3' UTR.
AB  - In animals, microRNAs (miRNAs) bind to the 3' UTRs of their target mRNAs and
      interfere with translation, although the exact mechanism of inhibition of protein
      synthesis remains unclear. Functional miRNA-binding sites in the coding regions
      or 5' UTRs of endogenous mRNAs have not been identified. We studied the effect of
      introducing miRNA target sites into the 5' UTR of luciferase reporter mRNAs
      containing internal ribosome entry sites (IRESs), so that potential steric
      hindrance by a microribonucleoprotein complex would not interfere with the
      initiation of translation. In human HeLa cells, which express endogenous let-7a
      miRNA, the translational efficiency of these IRES-containing reporters with 5'
      let-7 complementary sites from the Caenorhabditis elegans lin-41 3' UTR was
      repressed. Similarly, the IRES-containing reporters were translationally
      repressed when human Ago2 was tethered to either the 5' or 3' UTR. Interestingly,
      the method of DNA transfection affected our ability to observe miRNA-mediated
      repression. Our results suggest that association with any position on a target
      mRNA is mechanistically sufficient for a microribonucleoprotein to exert
      repression of translation at some step downstream of initiation.

PMID- 17535907
TI  - A high-throughput siRNA library screen identifies osteogenic suppressors in human
      mesenchymal stem cells.
AB  - Tissue-specific (or adult) stem/progenitor cells are regarded as the source for
      normal tissue homeostasis and tissue repair. They also provide tremendous promise
      for regenerative medicine because of their capacity to proliferate and
      differentiate into a variety of mature cell types. Human mesenchymal stem cells
      (hMSCs) can differentiate into osteocytes, adipocytes, chondrocytes, muscle
      cells, and neurons. However, the molecular mechanisms underlying these
      differentiation processes are poorly understood. We screened a synthetic siRNA
      library targeting 5,000 human genes to identify the endogenous repressors of
      osteogenic specification, which when silenced could initiate differentiation of
      hMSCs into osteoblasts. This screen yielded 53 candidate suppressors, and 12 of
      those were further confirmed for their dynamic roles in suppressing osteogenic
      specification in hMSCs. Furthermore, cAMP was identified to play opposing roles
      in osteogenesis vs. adipogenesis. This study provides a basis for further
      elucidation of the genetic network controlling osteogenesis and, potentially, the
      molecular rationale for treating bone diseases.

PMID- 17535908
TI  - Mechanisms for climate-induced mortality of fish populations in whole-lake
      experiments.
AB  - The effects of climate change on plant and animal populations are widespread and
      documented for many species in many areas of the world. However, projections of
      climate impacts will require a better mechanistic understanding of ecological and
      behavioral responses to climate change and climate variation. For vertebrate
      animals, there is an absence of whole-system manipulative experiments that
      express natural variation in predator and prey behaviors. Here we investigate the
      effect of elevated water temperature on the physiology, behavior, growth, and
      survival of fish populations in a multiple whole-lake experiment, by using 17
      lake-years of data collected over 2 years with differing average temperatures. We
      found that elevated temperatures in excess of the optimum reduced the scope for
      growth through reduced maximum consumption and increased metabolism in young
      rainbow trout, Oncorhynchus mykiss. Increased metabolism at high temperatures
      resulted in increased feeding activity (consumption) by individuals to compensate
      and maintain growth rates similar to that observed at cooler (optimum)
      temperatures. However, greater feeding activity rates resulted in greater
      vulnerability to predators that reduced survival to only half that of the cooler
      year. Our work therefore identifies temperature-dependent physiology and
      compensatory feeding behavior as proximate mechanisms for substantial climate
      induced mortality in fish populations at the scale of entire populations and
      waterbodies.

PMID- 17535909
TI  - Mechanism of the 5-hydroxytryptamine 2A receptor-mediated facilitation of
      synaptic activity in prefrontal cortex.
AB  - Classic hallucinogens such as lysergic acid diethylamide are thought to elicit
      their psychotropic actions via serotonin receptors of the 5-hydroxytryptamine 2A
      subtype (5-HT(2A)R). One likely site for these effects is the prefrontal cortex
      (PFC). Previous studies have shown that activation of 5-HT(2A)Rs in this region
      results in a robust increase in spontaneous glutamatergic synaptic activity, and
      these results have led to the widely held idea that hallucinogens elicit their
      effect by modulating synaptic transmission within the PFC. Here, we combine
      cellular and molecular biological approaches, including single-cell 5-HT(2A)Rs
      inactivation and 5-HT(2A)R rescue over a 5-HT(2A)R knockout genetic background,
      to distinguish between competing hypotheses accounting for these effects. The
      results from these experiments do not support the idea that 5-HT(2A)Rs elicit the
      release of an excitatory retrograde messenger nor that they activate
      thalamocortical afferents, the two dominant hypotheses. Rather, they suggest that
      5-HT(2A)Rs facilitate intrinsic networks within the PFC. Consistent with this
      idea, we locate a discrete subpopulation of pyramidal cells that is strongly
      excited by 5-HT(2A)R activation.

PMID- 17535910
TI  - Bacteriorhodopsin photocycle at cryogenic temperatures reveals distributed
      barriers of conformational substates.
AB  - The time course of thermal reactions after illumination of 100% humidified
      bacteriorhodopsin films was followed with FTIR spectroscopy between 125 and 195
      K. We monitored the conversion of the initial photoproduct, K, to the next, L
      intermediate, and a shunt reaction of the L state directly back to the initial BR
      state. Both reactions can be described by either multiexponential kinetics, which
      would lead to apparent end-state mixtures that contain increasing amounts of the
      product, i.e., L or BR, with increasing temperature, or distributed kinetics.
      Conventional kinetic schemes that could account for the partial conversion
      require reversible reactions, branching, or parallel cycles. These possibilities
      were tested by producing K or L and monitoring their interconversion at a single
      temperature and by shifting the temperature upward or downward after an initial
      incubation and after their redistribution. The results are inconsistent with any
      conventional scheme. Instead, we attribute the partial conversions to the other
      alternative, distributed kinetics, observed previously in myoglobin, which arise
      from an ensemble of frozen conformational substates at the cryogenic
      temperatures. In this case, the time course of the reactions reflects the
      progressive depletion of distinct microscopic substates in the order of their
      increasing activation barriers, with a distribution width for K to L reaction of
      approximately 7 kJ/mol.

PMID- 17535911
TI  - Free methionine-(R)-sulfoxide reductase from Escherichia coli reveals a new GAF
      domain function.
AB  - The reduction of methionine sulfoxide (MetO) is mediated by methionine sulfoxide
      reductases (Msr). The MsrA and MsrB families can reduce free MetO and MetO within
      a peptide or protein context. This process is stereospecific with the S- and R
      forms of MetO repaired by MsrA and MsrB, respectively. Cell extracts from an
      MsrA(-)B(-) knockout of Escherichia coli have several remaining Msr activities.
      This study has identified an enzyme specific for the free form of Met-(R)-O,
      fRMsr, through proteomic analysis. The recombinant enzyme exhibits the same
      substrate specificity and is as active as MsrA family members. E. coli fRMsr is,
      however, 100- to 1,000-fold more active than non-selenocysteine-containing MsrB
      enzymes for free Met-(R)-O. The crystal structure of E. coli fRMsr was previously
      determined, but no known function was assigned. Thus, the function of this
      protein has now been determined. The structural similarity of the E. coli and
      yeast proteins suggests that most fRMsrs use three cysteine residues for
      catalysis and the formation of a disulfide bond to enclose a small active site
      cavity. This latter feature is most likely a key determinant of substrate
      specificity. Moreover, E. coli fRMsr is the first GAF domain family member to
      show enzymatic activity. Other GAF domain proteins substitute the Cys residues
      and others to specifically bind cyclic nucleotides, chromophores, and many other
      ligands for signal potentiation. Therefore, Met-(R)-O may represent a signaling
      molecule in response to oxidative stress and nutrients via the TOR pathway in
      some organisms.

PMID- 17535912
TI  - Conformational variability of the intracellular domain of Drosophila Notch and
      its interaction with Suppressor of Hairless.
AB  - The Notch receptor is the central element in an evolutionarily conserved signal
      transduction pathway that controls cell fates in metazoans. Receptor-ligand
      interactions trigger a cascade of proteolytic events that release the entire
      Notch intracellular domain (NICD) from the membrane, permitting its translocation
      into the nucleus and participation in a transcriptionally active complex. Using
      electron microscopy, we examined the structure of NICD and its interaction with
      the DNA-binding effector of Notch signaling, Suppressor of Hairless [Su(H)]. In
      conjunction with biochemical analyses, we found that Drosophila NICD is monomeric
      and exists in two primary conformational states, only one of which can bind
      Su(H). Furthermore, we show that changes in divalent cation concentrations lead
      to NICD self-association, which seems to be mediated by the polyglutamine
      containing, opa-repeat region of NICD. Our study suggests that conformational
      modulation of NICD may define a mechanism of Notch pathway control.

PMID- 17535913
TI  - Formation of native prions from minimal components in vitro.
AB  - The conformational change of a host protein, PrP(C), into a disease-associated
      isoform, PrP(Sc), appears to play a critical role in the pathogenesis of prion
      diseases such as Creutzfeldt-Jakob disease and scrapie. However, the fundamental
      mechanism by which infectious prions are produced in neurons remains unknown. To
      investigate the mechanism of prion formation biochemically, we conducted a series
      of experiments using the protein misfolding cyclic amplification (PMCA) technique
      with a preparation containing only native PrP(C) and copurified lipid molecules.
      These experiments showed that successful PMCA propagation of PrP(Sc) molecules in
      a purified system requires accessory polyanion molecules. In addition, we found
      that PrP(Sc) molecules could be formed de novo from these defined components in
      the absence of preexisting prions. Inoculation of samples containing either prion
      seeded or spontaneously generated PrP(Sc) molecules into hamsters caused scrapie,
      which was transmissible on second passage. These results show that prions able to
      infect wild-type hamsters can be formed from a minimal set of components
      including native PrP(C) molecules, copurified lipid molecules, and a synthetic
      polyanion.

PMID- 17535914
TI  - A specific c-type cytochrome maturation system is required for oxygenic
      photosynthesis.
AB  - Oxygenic photosynthesis is an important bioenergetic process that maintains the
      Earth's atmosphere and allows carbon fixation. A critical enzyme in this process,
      the cytochrome b(6)f complex, differs from other protein complexes of the same
      family by an unusual covalently attached cofactor chemically defined as a c'
      heme. We have identified a set of pioneer proteins that carry the biogenesis of
      this c' heme and started their characterization. They are encoded by the genomes
      of all organisms performing oxygenic photosynthesis, whatever their phylogenetic
      distances. These proteins are thus among the few that distinguish photosynthetic
      cells evolving oxygen from other types of living cells.

PMID- 17535915
TI  - Sumoylation of nucleophosmin/B23 regulates its subcellular localization,
      mediating cell proliferation and survival.
AB  - Nucleophosmin/B23 is a major multifunctional nucleolar phosphoprotein that plays
      a critical role in ribosome biogenesis and cell proliferation. Arf tumor
      suppressor binds B23 and enhances its sumoylation. However, the biological
      effects of this event remain unknown. Here we show that B23 is sumoylated on both
      Lysine 230 and 263 residues, but the latter is the major one. Mutation of K263,
      but not K230, into R abolishes its centrosomal and nucleolar residency. Moreover,
      Rb binds to wild-type B23, but fails to interact with K263R. Sumoylation enhances
      B23 binding to Rb. Consequently, B23 potently stimulates E2F1-mediated
      transcriptional activity, which is abolished in B23 K263R. Further, K263R
      mutation makes B23 vulnerable to caspase-3 cleavage and sensitizes cells to
      apoptosis. Surprisingly, K230R mutant strongly binds to phosphatidylinositol
      3,4,5-trisphosphate and suppresses DNA fragmentation. Thus, B23 sumoylation
      regulates its subcellular localization, cell proliferation, and survival
      activities.

PMID- 17535916
TI  - Small-molecule activators of RNase L with broad-spectrum antiviral activity.
AB  - RNase L, a principal mediator of innate immunity to viral infections in higher
      vertebrates, is required for a complete IFN antiviral response against certain
      RNA stranded viruses. dsRNA produced during viral infections activates IFN
      inducible synthetases that produce 5'-phosphorylated, 2',5'-oligoadenylates (2
      5A) from ATP. 2-5A activates RNase L in a wide range of different mammalian cell
      types, thus blocking viral replication. However, 2-5A has unfavorable
      pharmacologic properties; it is rapidly degraded, does not transit cell
      membranes, and leads to apoptosis. To obtain activators of RNase L with improved
      drug-like properties, high-throughput screening was performed on chemical
      libraries by using fluorescence resonance energy transfer. Seven compounds were
      obtained that activated RNase L at micromolar concentrations, and structure
      activity relationship studies resulted in identification of an additional four
      active compounds. Two lead compounds were shown to have a similar mechanistic
      path toward RNase L activation as the natural activator 2-5A. The compounds bound
      to the 2-5A-binding domain of RNase L (as determined by surface plasmon resonance
      and confirmed by computational docking), and the compounds induced RNase L
      dimerization and activation. Interestingly, the low-molecular-weight activators
      of RNase L had broad-spectrum antiviral activity against diverse types of RNA
      viruses, including the human pathogen human parainfluenza virus type 3, yet these
      compounds by themselves were not cytotoxic at the effective concentrations.
      Therefore, these RNase L activators are prototypes for a previously
      uncharacterized class of broad-spectrum antiviral agents.

PMID- 17535917
TI  - Mastermind-1 is required for Notch signal-dependent steps in lymphocyte
      development in vivo.
AB  - Mastermind (Mam) is one of the elements of Notch signaling, an ancient system
      that plays a pivotal role in metazoan development. Genetic analyses in Drosophila
      and Caenorhabditis elegans have shown Mam to be an essential positive regulator
      of this signaling pathway in these species. Mam proteins bind to and stabilize
      the DNA-binding complex of the intracellular domains of Notch and CBF-1, Su(H),
      Lag-1 (CSL) DNA-binding proteins in the nucleus. Mammals have three Mam proteins,
      which show remarkable similarities in their functions while having an unusual
      structural diversity. There have also been recent indications that Mam-1
      functionally interacts with other transcription factors including p53 tumor
      suppressor. We herein describe that Mam-1 deficiency in mice abolishes the
      development of splenic marginal zone B cells, a subset strictly dependent on
      Notch2, a CSL protein and Delta1 ligand. Mam-1 deficiency also causes a partially
      impaired development of early thymocytes, while not affecting the generation of
      definitive hematopoiesis, processes that are dependent on Notch1. We also
      demonstrate the transcriptional activation of a target promoter by constitutively
      active forms of Notch to decrease severalfold in cultured Mam-1-deficient cells.
      These results indicate that Mam-1 is thus required to some extent for Notch
      dependent stages in lymphopoiesis, thus supporting the notion that Mam is an
      essential component of the canonical Notch pathway in mammals.

PMID- 17535918
TI  - Zinc finger protein STOP1 is critical for proton tolerance in Arabidopsis and
      coregulates a key gene in aluminum tolerance.
AB  - Acid soil syndrome causes severe yield losses in various crop plants because of
      the rhizotoxicities of ions, such as aluminum (Al(3+)). Although protons (H(+))
      could be also major rhizotoxicants in some soil types, molecular mechanisms of
      their tolerance have not been identified yet. One mutant that was hypersensitive
      to H(+) rhizotoxicity was isolated from ethyl methanesulfonate mutagenized seeds,
      and a single recessive mutation was found on chromosome 1. Positional cloning
      followed by genomic sequence analysis revealed that a missense mutation in the
      zinc finger domain in a predicted Cys(2)His(2)-type zinc finger protein, namely
      sensitive to proton rhizotoxicity (STOP)1, is the cause of hypersensitivity to
      H(+) rhizotoxicity. The STOP1 protein belongs to a functionally unidentified
      subfamily of zinc finger proteins, which consists of two members in Arabidopsis
      based on a Blast search. The stop1 mutation resulted in no effects on cadmium,
      copper, lanthanum, manganese and sodium chloride sensitivitities, whereas it
      caused hypersensitivity to Al(3+) rhizotoxicity. This stop1 mutant lacked the
      induction of the AtALMT1 gene encoding a malate transporter, which is concomitant
      with Al-induced malate exudation. There was no induction of AtALMT1 by Al(3+)
      treatment in the stop1 mutant. These results indicate that STOP1 plays a critical
      role in Arabidopsis tolerance to major stress factors in acid soils.

PMID- 17535919
TI  - The hotei mutation of medaka in the anti-Mullerian hormone receptor causes the
      dysregulation of germ cell and sexual development.
AB  - We previously performed mutant screens in the medaka for defects in gonadal
      development and identified a mutant of interest in this regard, which was
      designated as hotei (hot). This mutant manifests a number of remarkable
      phenotypic abnormalities including: (i) excessive proliferation of germ cells
      that initiates at around the hatching stage regardless of the genetic sex of the
      fish; (ii) initiation of premature meiosis in phenotypically male hot
      homozygotes; (iii) one-half of the hot-homozygous XY fish undergo sex reversal,
      which accompanies the expression of the female-characteristic aromatase gene in
      the somatic cells of the gonad; and (iv) in phenotypically female homozygotes,
      follicular development is arrested at an early stage. We have also performed
      genetic mapping, chromosome walking, and candidate gene sequencing analysis of
      hot and demonstrate that the underlying mutation occurs in the recently
      identified medaka anti-Mullerian hormone (Amh) receptor type II (amhrII) gene.
      Moreover, this gene was found to be responsible for each of the hot phenotypes,
      as an amhrII transgene rescues these abnormalities. In addition, the amhrII gene
      is expressed in the somatic cells of the gonads of both sexes. The phenotypes of
      the hot homozygotes indicate that there are multiple regulatory functions of the
      AMH/AMHRII signaling system in the development of the gonad, including the sex
      dependent regulation of germ cell proliferation and follicular development. These
      presumably represent the basic roles of Amh, which precede Mullerian duct
      evolution during phylogeny.

PMID- 17535920
TI  - Dominant factors controlling glacial and interglacial variations in the treeline
      elevation in tropical Africa.
AB  - The knowledge of tropical palaeoclimates is crucial for understanding global
      climate change, because it is a test bench for general circulation models that
      are ultimately used to predict future global warming. A longstanding issue
      concerning the last glacial maximum in the tropics is the discrepancy between the
      decrease in sea-surface temperatures reconstructed from marine proxies and the
      high-elevation decrease in land temperatures estimated from indicators of
      treeline elevation. In this study, an improved inverse vegetation modeling
      approach is used to quantitatively reconstruct palaeoclimate and to estimate the
      effects of different factors (temperature, precipitation, and atmospheric CO(2)
      concentration) on changes in treeline elevation based on a set of pollen data
      covering an altitudinal range from 100 to 3,140 m above sea level in Africa. We
      show that lowering of the African treeline during the last glacial maximum was
      primarily triggered by regional drying, especially at upper elevations, and was
      amplified by decreases in atmospheric CO(2) concentration and perhaps
      temperature. This contrasts with scenarios for the Holocene and future climates,
      in which the increase in treeline elevation will be dominated by temperature. Our
      results suggest that previous temperature changes inferred from tropical treeline
      shifts may have been overestimated for low-CO(2) glacial periods, because the
      limiting factors that control changes in treeline elevation differ between
      glacial and interglacial periods.

PMID- 17535921
TI  - Designing an extracellular matrix protein with enhanced mechanical stability.
AB  - The extracellular matrix proteins tenascin and fibronectin experience significant
      mechanical forces in vivo. Both contain a number of tandem repeating homologous
      fibronectin type III (fnIII) domains, and atomic force microscopy experiments
      have demonstrated that the mechanical strength of these domains can vary
      significantly. Previous work has shown that mutations in the core of an fnIII
      domain from human tenascin (TNfn3) reduce the unfolding force of that domain
      significantly: The composition of the core is apparently crucial to the
      mechanical stability of these proteins. Based on these results, we have used
      rational redesign to increase the mechanical stability of the 10th fnIII domain
      of human fibronectin, FNfn10, which is directly involved in integrin binding. The
      hydrophobic core of FNfn10 was replaced with that of the homologous, mechanically
      stronger TNfn3 domain. Despite the extensive substitution, FNoTNc retains both
      the three-dimensional structure and the cell adhesion activity of FNfn10. Atomic
      force microscopy experiments reveal that the unfolding forces of the engineered
      protein FNoTNc increase by approximately 20% to match those of TNfn3. Thus, we
      have specifically designed a protein with increased mechanical stability. Our
      results demonstrate that core engineering can be used to change the mechanical
      strength of proteins while retaining functional surface interactions.

PMID- 17535922
TI  - The B''/PR72 subunit mediates Ca2+-dependent dephosphorylation of DARPP-32 by
      protein phosphatase 2A.
AB  - In dopaminoceptive neurons, dopamine- and cAMP-regulated phosphoprotein of 32 kDa
      (DARPP-32) plays a central role in integrating the effects of dopamine and other
      neurotransmitters. Phosphorylation of DARPP-32 at Thr-34 by protein kinase A
      results in inhibition of protein phosphatase 1 (PP1), and phosphorylation at Thr
      75 by Cdk5 (cyclin-dependent kinase 5) results in inhibition of protein kinase A.
      Dephosphorylation at Thr-34 involves primarily the Ca(2+)-dependent protein
      phosphatase, PP2B (calcineurin), whereas dephosphorylation of Thr-75 involves
      primarily PP2A, the latter being subject to control by both cAMP- and Ca(2+)
      dependent regulatory mechanisms. In the present study, we have investigated the
      mechanism of Ca(2+)-dependent regulation of Thr-75 by PP2A. We show that the PR72
      (or B'' or PPP2R3A) regulatory subunit of PP2A is highly expressed in striatum.
      Through the use of overexpression and down-regulation by using RNAi, we show that
      PP2A, in a heterotrimeric complex with the PR72 subunit, mediates Ca(2+)
      dependent dephosphorylation at Thr-75 of DARPP-32. The PR72 subunit contains two
      Ca(2+) binding sites formed by E and F helices (EF-hands 1 and 2), and we show
      that the former is necessary for the ability of PP2A activity to be regulated by
      Ca(2+), both in vitro and in vivo. Our studies also indicate that the PR72
      containing form of PP2A is necessary for the ability of glutamate acting at alpha
      amino-3-hydroxy-5-methylisoxazole-4-propionic acid and NMDA receptors to regulate
      Thr-75 dephosphorylation. These studies further our understanding of the complex
      signal transduction pathways that regulate DARPP-32. In addition, our studies
      reveal an alternative intracellular mechanism whereby Ca(2+) can activate
      serine/threonine phosphatase activity.

PMID- 17535923
TI  - Chemomechanical mapping of ligand-receptor binding kinetics on cells.
AB  - The binding kinetics between cell surface receptors and extracellular
      biomolecules is critical to all intracellular and intercellular activity.
      Modeling and prediction of receptor-mediated cell functions are facilitated by
      measurement of the binding properties on whole cells, ideally indicating the
      subcellular locations or cytoskeletal associations that may affect the function
      of bound receptors. This dual need is particularly acute vis a vis ligand
      engineering and clinical applications of antibodies to neutralize pathological
      processes. Here, we map individual receptors and determine whole-cell binding
      kinetics by means of functionalized force imaging, enabled by scanning probe
      microscopy and molecular force spectroscopy of intact cells with biomolecule
      conjugated mechanical probes. We quantify the number, distribution, and
      association/dissociation rate constants of vascular endothelial growth factor
      receptor-2 with respect to a monoclonal antibody on both living and fixed human
      microvascular endothelial cells. This general approach to direct receptor imaging
      simultaneously quantifies both the binding kinetics and the nonuniform
      distribution of these receptors with respect to the underlying cytoskeleton,
      providing spatiotemporal visualization of cell surface dynamics that regulate
      receptor-mediated behavior.

PMID- 17535924
TI  - Transcription factor Sp4 regulates dendritic patterning during cerebellar
      maturation.
AB  - Integration of inputs by a neuron depends on dendritic arborization patterns. In
      mammals, the genetic programs that regulate dynamic remodeling of dendrites
      during development and in response to activity are incompletely understood. Here
      we report that knockdown of the transcription factor Sp4 led to an increased
      number of highly branched dendrites during maturation of cerebellar granule
      neurons in dissociated cultures and in cerebellar cortex. Time-course analysis
      revealed that depletion of Sp4 led to persistent generation of dendritic branches
      and a failure in resorption of transient dendrites. Depolarization induced a
      reduction in the number of dendrites, and knockdown of Sp4 blocked depolarization
      induced remodeling. Furthermore, overexpression of Sp4 wild type, but not a
      mutant lacking the DNA-binding domain, was sufficient to promote dendritic
      pruning in nondepolarizing conditions. These findings indicate that the
      transcription factor Sp4 controls dendritic patterning during cerebellar
      development by limiting branch formation and promoting activity-dependent
      pruning.

PMID- 17535925
TI  - In vitro high-resolution structural dynamics of single germinating bacterial
      spores.
AB  - Although significant progress has been achieved in understanding the genetic and
      biochemical bases of the spore germination process, the structural basis for
      breaking the dormant spore state remains poorly understood. We have used atomic
      force microscopy (AFM) to probe the high-resolution structural dynamics of single
      Bacillus atrophaeus spores germinating under native conditions. Here, we show
      that AFM can reveal previously unrecognized germination-induced alterations in
      spore coat architecture and topology as well as the disassembly of outer spore
      coat rodlet structures. These results and previous studies in other
      microorganisms suggest that the spore coat rodlets are structurally similar to
      amyloid fibrils. AFM analysis of the nascent surface of the emerging germ cell
      revealed a porous network of peptidoglycan fibers. The results are consistent
      with a honeycomb model structure for synthetic peptidoglycan oligomers determined
      by NMR. AFM is a promising experimental tool for investigating the morphogenesis
      of spore germination and cell wall peptidoglycan structure.

PMID- 17535926
TI  - Newcastle disease virus, a host range-restricted virus, as a vaccine vector for
      intranasal immunization against emerging pathogens.
AB  - The international outbreak of the severe acute respiratory syndrome-associated
      coronavirus (SARS-CoV) in 2002-2003 highlighted the need to develop pretested
      human vaccine vectors that can be used in a rapid response against newly emerging
      pathogens. We evaluated Newcastle disease virus (NDV), an avian paramyxovirus
      that is highly attenuated in primates, as a topical respiratory vaccine vector
      with SARS-CoV as a test pathogen. Complete recombinant NDV was engineered to
      express the SARS-CoV spike S glycoprotein, the viral neutralization and major
      protective antigen, from an added transcriptional unit. African green monkeys
      immunized through the respiratory tract with two doses of the vaccine developed a
      titer of SARS-CoV-neutralizing antibodies comparable with the robust secondary
      response observed in animals that have been immunized with a different
      experimental SARS-CoV vaccine and challenged with SARS-CoV. When animals
      immunized with NDV expressing S were challenged with a high dose of SARS-CoV,
      direct viral assay of lung tissues taken by necropsy at the peak of viral
      replication demonstrated a 236- or 1,102-fold (depending on the NDV vector
      construct) mean reduction in pulmonary SARS-CoV titer compared with control
      animals. NDV has the potential for further development as a pretested, highly
      attenuated, intranasal vector to be available for expedited vaccine development
      for humans, who generally lack preexisting immunity against NDV.

PMID- 17535927
TI  - Oxygen metabolism and reactive oxygen species cause chromosomal rearrangements
      and cell death.
AB  - The absence of Tsa1, a key peroxiredoxin that functions to scavenge H(2)O(2) in
      Saccharomyces cerevisiae, causes the accumulation of a broad spectrum of
      mutations including gross chromosomal rearrangements (GCRs). Deletion of TSA1
      also causes synthetic lethality in combination with mutations in RAD6 and several
      key genes involved in DNA double-strand break repair. In the present study we
      investigated the causes of GCRs and cell death in these mutants. tsa1-associated
      GCRs were independent of the activity of the translesion DNA polymerases zeta,
      eta, and Rev1. Anaerobic growth reduced substantially GCR rates of WT and tsa1
      mutants and restored the viability of tsa1 rad6, tsa1 rad51, and tsa1 mre11
      double mutants. Anaerobic growth also reduced the GCR rate of rad27, pif1, and
      rad52 mutants, indicating a role of reactive oxygen species in GCR formation in
      these mutants. In addition, deletion of TSA1 or H(2)O(2) treatment of WT cells
      resulted in increased formation of Rad52 foci, sites of repair of multiple DNA
      lesions. H(2)O(2) treatment also induced the GCRs. Our results provide in vivo
      evidence that oxygen metabolism and reactive oxygen species are important sources
      of DNA damages that can lead to GCRs and lethal effects in S. cerevisiae.

PMID- 17535928
TI  - Sex chromosome silencing in the marsupial male germ line.
AB  - In marsupials, dosage compensation involves silencing of the father's X
      chromosome. Because no XIST orthologue has been found, how imprinted X
      inactivation occurs is unknown. In eutherians, the X is subject to meiotic sex
      chromosome inactivation (MSCI) in the paternal germ line and persists thereafter
      as postmeiotic sex chromatin (PMSC). One hypothesis proposes that the paternal X
      is inherited by the eutherian zygote as a preinactive X and raises the
      possibility of a similar process in the marsupial germ line. Here we demonstrate
      that MSCI and PMSC occur in the opossum. Surprisingly, silencing occurs before X
      Y association. After MSCI, the X and Y fuse through a dense plate without obvious
      synapsis. Significantly, sex chromosome silencing continues after meiosis, with
      the opossum PMSC sharing features of eutherian PMSC. These results reveal a
      common gametogenic program in two diverse clades of mammals and support the idea
      that male germ-line silencing may have provided an ancestral form of mammalian
      dosage compensation.

PMID- 17535929
TI  - Purkinje cell dysfunction and alteration of long-term synaptic plasticity in
      fetal alcohol syndrome.
AB  - In cerebellum and other brain regions, neuronal cell death because of ethanol
      consumption by the mother is thought to be the leading cause of neurological
      deficits in the offspring. However, little is known about how surviving cells
      function. We studied cerebellar Purkinje cells in vivo and in vitro to determine
      whether function of these cells was altered after prenatal ethanol exposure. We
      observed that Purkinje cells that were prenatally exposed to ethanol presented
      decreased voltage-gated calcium currents because of a decreased expression of the
      gamma-isoform of protein kinase C. Long-term depression at the parallel fiber
      Purkinje cell synapse in the cerebellum was converted into long-term
      potentiation. This likely explains the dramatic increase in Purkinje cell firing
      and the rapid oscillations of local field potential observed in alert fetal
      alcohol syndrome mice. Our data strongly suggest that reversal of long-term
      synaptic plasticity and increased firing rates of Purkinje cells in vivo are
      major contributors to the ataxia and motor learning deficits observed in fetal
      alcohol syndrome. Our results show that calcium-related neuronal dysfunction is
      central to the pathogenesis of the neurological manifestations of fetal alcohol
      syndrome and suggest new methods for treatment of this disorder.

PMID- 17535931
TI  - Can mandated outpatient treatment prevent tragedies?

PMID- 17535930
TI  - Functional redundancy of worm spliceosomal proteins U1A and U2B''.
AB  - In Caenorhabditis elegans, the small nuclear ribonucleoprotein (snRNP)-associated
      proteins U1A and U2B'' are approximately 50% identical to each other, and neither
      bears signature characteristics of mammalian U1A or U2B'' or the single
      Drosophila homolog, SNF. We show here that the genes that encode these proteins
      (rnp-2 and rnp-3) are cotranscribed in an operon, and that ribonucleoprotein RNP
      2 is U1 snRNP-associated (U1A) whereas RNP-3 is U2 snRNP-associated (U2B'').
      U2B'' interacts with U2 even in the absence of another U2 snRNP protein, U2A'.
      Like U1A and U2B'' from yeast, plants, and vertebrates, worm U1A and U2B'' are
      more similar to each other than they are to other U1A or U2B'' proteins,
      respectively. Even though U1A and U2B'' interact with different snRNPs, they are
      functionally redundant; knockout of both is required for a lethal phenotype.
      Interestingly, U1A associates with U2 RNA when U2B'' is deleted. Thus, the two
      members of this gene family normally function as components of different snRNPs
      but apparently remain capable of performing the function of the other. Redundancy
      results from the fact that one protein can substitute for the other, even though
      it normally does not.

PMID- 17535932
TI  - Datapoints: self-reported access to general medical and psychiatric care among
      veterans with bipolar disorder.

PMID- 17535933
TI  - Innovations: clinical computing: an audio computer-assisted self-interviewing
      system for research and screening in public mental health settings.
AB  - This column describes the nonproprietary software Talker, used to adapt screening
      instruments to audio computer-assisted self-interviewing (ACASI) systems for low
      literacy populations and other populations. Talker supports ease of programming,
      multiple languages, on-site scoring, and the ability to update a central research
      database. Key features include highly readable text display, audio presentation
      of questions and audio prompting of answers, and optional touch screen input. The
      scripting language for adapting instruments is briefly described as well as two
      studies in which respondents provided positive feedback on its use.

PMID- 17535934
TI  - Best practices: comparing medication treatments in mental health: drug class
      reviews and policy challenges.
AB  - Advances in the number and type of medications for psychiatric illness have
      substantially aided physicians. However, as the number of available medications
      within a class increases, so does the complexity in decision making for provider
      and patient. Systematic review of a class of medications can assist providers in
      drug choice. The purpose and methods of such drug class reviews are described.
      Critical elements of a quality review include the choice of the question,
      explicit eligibility criteria, systematic search of the literature, article
      abstraction, and sometimes pooling of the data by using meta-analysis with direct
      or indirect comparison of study findings. Best practices are suggested for
      clinicians, administrators, and policy makers to consider when using drug class
      reviews in clinical organizations. The number of drug class reviews is
      increasing, and they have the potential to significantly assist providers,
      patients, and payers.

PMID- 17535935
TI  - Personal accounts: who are "they"?

PMID- 17535936
TI  - Understanding and preventing criminal recidivism among adults with psychotic
      disorders.
AB  - The high prevalence of adults with psychotic disorders in the criminal justice
      system has received much attention recently, but our understanding of this
      problem is marked by diverging opinions. Mental health professionals point to
      deinstitutionalization and our fragmented mental health system as primary causes.
      Criminologists minimize the role of mental illness and contend that persons with
      and without mental illness are arrested for the same reasons. Meanwhile, practice
      guidelines offer little guidance to clinicians about how to address the problem.
      Drawing upon contemporary crime prevention principles as well as current
      knowledge of psychotic disorders and their treatment, this article presents a
      conceptual framework for understanding and preventing criminal recidivism. The
      framework highlights the importance of individual and service-system risk
      variables and emphasizes the central role of treatment nonadherence as a mediator
      between modifiable risk variables and recidivism. On the basis of the conceptual
      framework described in this article, three necessary elements of intervention are
      presented for preventing recidivism among adults with psychotic disorders:
      competent care, access to services, and legal leverage. Research is needed to
      further define and test these intervention elements as foundations for future
      service delivery efforts.

PMID- 17535937
TI  - Treatment prospects for persons with severe mental illness in an urban county
      jail.
AB  - OBJECTIVE: A retrospective study of inmates with severe mental illness in a
      large, urban county jail aimed to obtain information about their psychiatric and
      criminal histories and status, the psychiatric services they used while
      incarcerated, and the challenges they might present in psychiatric treatment
      after release. METHODS: The authors ascertained demographic characteristics,
      diagnoses, psychiatric and legal histories, and current psychiatric condition and
      treatment from jail psychiatric records of a random sample of 104 male inmates
      with mental illness and from electronic county mental health records and state
      records of criminal histories. RESULTS: Seventy-eight inmates (75%) were
      diagnosed as having a severe mental illness. Of these, 59 (76%) required
      inpatient care or its equivalent for part of their time in jail for the current
      offense. Of the inmates with severe mental illness, 92% had a history of
      nonadherence to medications before this arrest, 95% had prior arrests, 72% had
      prior arrests for violent crimes against persons, and 76% were known to have a
      history of substance abuse. CONCLUSIONS: A large percentage of persons with
      severe mental illness received their acute psychiatric inpatient treatment in the
      criminal justice system rather than in the mental health system. The persons with
      severe mental illness in this study would present a major challenge in treatment
      in any setting given their psychiatric and criminal histories. The resources of
      the mental health system need to be greatly expanded, with priority given to
      treating persons who are criminalized or who are in danger of becoming
      criminalized.

PMID- 17535938
TI  - Applying procedural justice theory to law enforcement's response to persons with
      mental illness.
AB  - Procedural justice provides a framework for considering how persons with mental
      illness experience interactions with the police and how officer behaviors may
      shape cooperation or resistance. The procedural justice perspective holds that
      the fairness with which people are treated in an encounter with authority figures
      (such as the police) influences whether they cooperate or resist authority. Key
      components of a procedural justice framework include participation (having a
      voice), which involves having the opportunity to present one's own side of the
      dispute and be heard by the decision maker; dignity, which includes being treated
      with respect and politeness and having one's rights acknowledged; and trust that
      the authority is concerned with one's welfare. Procedural justice has its
      greatest impact early in the encounter, suggesting that how officers initially
      approach someone is extremely important. Persons with mental illness may be
      particularly attentive to how they are treated by police. According to this
      framework, people who are uncertain about their status (such as members of
      stigmatized groups) will respond most strongly to the fairness by which police
      exercise their authority. This article reviews the literature on police response
      to persons with mental illness. Procedural justice theory as it has been applied
      to mental health and justice system contexts is examined. Its application to
      encounters between police and persons with mental illness is discussed.
      Implications and cautions for efforts to improve police response to persons with
      mental illness and future research also are examined.

PMID- 17535939
TI  - The role of Medicaid enrollment and outpatient service use in jail recidivism
      among persons with severe mental illness.
AB  - OBJECTIVE: This study sought to determine whether having Medicaid benefits and
      receiving behavioral health services are associated with a reduction in
      recidivism for jail detainees with severe mental illness. METHODS: A quasi
      experimental design with linked administrative data was used. All persons
      released over a two-year period from jails in King County, Washington (N=5,189),
      and Pinellas County, Florida (N=2,419), who had severe mental illness were
      followed for 12 months after jail release. Those who were receiving Medicaid
      benefits at release and those who were not were compared on three indicators: how
      many subsequent arrests occurred, how soon the arrest occurred, and how serious
      the associated offense was. The data were analyzed with negative binomial, Cox
      proportional hazards models and logistic regression with adjustments for
      dependent observations. RESULTS: In both counties, having Medicaid at release was
      associated with a 16% reduction in the average number of subsequent detentions
      (p<.001 and p<.01, respectively). After the analysis controlled for demographic
      and clinical variables, more days on Medicaid were associated with a reduced
      number of subsequent detentions in King County (p<.001) and more days in the
      community before subsequent arrest in both counties (p<.01 and p<.05,
      respectively). No association was found between Medicaid status and the
      seriousness of the subsequent offense in either county. CONCLUSIONS: Although
      Medicaid benefits and behavioral health services were associated with fewer
      rearrests and more time in the community, the observed differences were
      relatively small. Further research is needed to determine how greater reductions
      in jail recidivism can be achieved for this target population.

PMID- 17535940
TI  - Adding consumer-providers to intensive case management: does it improve outcome?
AB  - OBJECTIVE: Over the past decade, there has been increasing interest in the
      employment of mental health consumers in various roles as providers of services.
      Although integration of consumers into case management services has been studied,
      the roles of consumers have been poorly defined and the benefits have not been
      established. The goal of this study was to evaluate whether consumers enhance
      case management outcome through the provision of social support. METHODS: This
      study compared consumer-assisted and non-consumer-assisted case management with
      standard clinic-based care. The consumer role focused on the development of
      social support by using peer staff who matched the profile of participants. A
      total of 203 clients with severe and persistent mental illness were randomly
      assigned to one of the three conditions and followed for 12 months. RESULTS: All
      three programs yielded the same general pattern of improvement over time for
      symptoms, health care satisfaction, and quality of life. Clients in the three
      programs also showed similar but small changes in measures of social network
      behavior. Consumer-assisted case management was unique in its use of peer
      organized activities. Non-consumer-assisted case management made greater use of
      individual contacts with professional staff. Standard clinic-based care relied
      more on group and on individual therapy. Despite these variations in the pattern
      of services over a 12-month period, no one program emerged as categorically
      superior to the others. CONCLUSIONS: Although more research is needed to
      determine optimal roles for consumers in mental health service delivery, a
      randomized trial found no evidence that the presence of consumers enhances case
      management outcome.

PMID- 17535941
TI  - Mental health care of Filipino Americans.
AB  - Filipino Americans are the second-fastest-growing Asian immigrant group in the
      United States, following the Chinese. Yet there exists a dearth of information on
      mental health issues concerning Filipino Americans, who represent a diverse
      mixture of culture, beliefs, and practices and vary widely from other minorities
      as well as from the larger population. This group has experienced emotional and
      behavioral challenges in acclimatizing to Western culture. Their historical
      underpinnings, native core values, and traditions exert a crucial influence on
      their mental well-being. Filipino Americans underutilize existing mental health
      care services that are culturally, socially, and linguistically incompatible with
      their needs. Along with stigma, the adherence of traditional practices and
      healing methods remains a formidable barrier to the appropriate provision of
      care. The authors review factors influencing perceptions of mental health and
      illness, including religion, family, support systems, coping styles, and
      indigenous culture-bound traits. Recommendations for treatment consist of a
      structured, culturally sensitive, comprehensive approach that addresses the
      individual as well as the cultural milieu.

PMID- 17535942
TI  - WHO's Assessment Instrument for Mental Health Systems: collecting essential
      information for policy and service delivery.
AB  - Information about mental health systems is essential for mental health planning
      to reduce the burden of neuropsychiatric disorders. Unfortunately, many low- and
      middle-income countries lack systematic information on their mental health
      systems. The objectives, scope, structure, and contents of mental health
      assessment and monitoring instruments commonly used in high-income countries may
      not be appropriate for use in middle- and low-income countries. The World Health
      Organization (WHO) has recently developed the WHO Assessment Instrument for
      Mental Health Systems (WHO-AIMS), a comprehensive assessment tool for mental
      health systems designed for middle- and low-income countries. WHO-AIMS was
      developed through an iterative process that included input from in-country and
      international experts on the clarity, content, validity, and feasibility of the
      instrument, as well as a pilot trial. The resulting instrument, WHO-AIMS 2.2,
      consists of six domains: policy and legislative framework, mental health
      services, mental health in primary care, human resources, public information and
      links with other sectors, and monitoring and research. These domains address the
      ten recommendations of the World Health Report 2001 through 28 facets and 155
      items. All six domains need to be assessed to form a basic, yet broad, picture of
      a mental health system, with a focus on health sector activities. WHO-AIMS
      provides essential information for mental health policy and service delivery.
      Countries will be able to develop information-based mental health policy and
      plans with clear baseline information and targets. Moreover, they will be able to
      monitor progress in implementing reform policies, providing community services,
      and involving consumers, families, and other stakeholders in mental health
      promotion, prevention, care and rehabilitation. This article provides an overview
      of the rationale, development process, and potential uses and benefits of WHO
      AIMS.

PMID- 17535943
TI  - Impact of intimate partner violence on unmet need for mental health care: results
      from the NSDUH.
AB  - OBJECTIVES: This study examined risk factors and ethnic differences in the
      relationship between intimate partner violence and unmet need for mental health
      treatment (perceived need for but did not receive treatment) in the general
      population. METHODS: The 2002 National Survey on Drug Use and Health was used;
      the analysis presented here included black, Hispanic, and non-Hispanic white
      women ages 18 to 49 who were cohabiting (N=7,924). Logistic regression was used
      to calculate adjusted odds ratios (AORs) and 95% confidence intervals (CIs).
      RESULTS: Victims of partner violence were twice as likely as nonvictims
      (AOR=2.11, CI=1.41-3.16) overall to report unmet need, after analyses controlled
      for socioeconomic factors and substance abuse. In ethnic-specific models, only
      Hispanic and non-Hispanic white women who experienced partner violence were more
      likely than their nonabused counterparts to report unmet need for treatment (AOR
      4.11, CI=1.34-12.60, and AOR=2.12, CI=1.34-3.35, respectively). CONCLUSIONS: This
      study suggests that women who experienced partner violence, especially Hispanic
      women, are at increased risk of not receiving needed mental health care. These
      findings highlight the need for culturally sensitive and specific outreach about
      the effects of partner violence on women's mental health and how to access these
      services.

PMID- 17535944
TI  - An economic evaluation of telehealth data collection with rural populations.
AB  - OBJECTIVE: This study compared direct costs of conducting structured clinical
      interviews via real-time interactive videoconferencing (known as telehealth)
      versus standard in-person methods with American Indians in rural locations.
      METHODS: Psychiatrists administered in person and via telehealth on two occasions
      the Structured Clinical Interview for DSM-III-R to 53 non-VA male, American
      Indian veterans. Telehealth interviews were conducted by an integrated services
      digital network (ISDN) connection at 384 kbps. Direct costs were compared for the
      two interview modalities. Models for starting telehealth in new clinics and
      established clinics were created, and the models were further subdivided to
      examine 2003 and 2005 differences in transmission fees. Direct costs included
      transmission, personnel, travel, and equipment (where applicable). RESULTS: The
      model of conducting interviews via telehealth in new clinics cost about $6,000
      more than in-person interviews in 2003. However, reduced transmission fees and a
      different videoconferencing setup resulted in telehealth interviews' costing
      $8,000 less than in-person interviews in 2005. The same pattern held true for the
      model for established clinics. Telehealth interviews cost $1,700 more than in
      person interviews in 2003 but $12,000 less in 2005. Scenarios using nonphysician
      interviewers and current, rather than historical, transmission costs favored
      telehealth as a cost-effective means for clinical research. CONCLUSIONS: On the
      basis of current transmission costs, telehealth proved less expensive than in
      person interviews. Telehealth may therefore increase the efficiency and decrease
      the cost of research with rural, remote, and underserved populations,
      facilitating the ease with which one can investigate health disparities in these
      otherwise neglected settings.

PMID- 17535945
TI  - Is telepsychiatry equivalent to face-to-face psychiatry? Results from a
      randomized controlled equivalence trial.
AB  - OBJECTIVE: The use of interactive videoconferencing to provide psychiatric
      services to geographically remote regions, often referred to as telepsychiatry,
      has gained wide acceptance. However, it is not known whether clinical outcomes of
      telepsychiatry are as good as those achieved through face-to-face contact. This
      study compared a variety of clinical outcomes after psychiatric consultation and,
      where needed, brief follow-up for outpatients referred to a psychiatric clinic in
      Canada who were randomly assigned to be examined face to face or by
      telepsychiatry. METHODS: A total of 495 patients in Ontario, Canada, referred by
      their family physician for psychiatric consultation were randomly assigned to be
      examined face to face (N=254) or by telepsychiatry (N=241). The treating
      psychiatrists had the option of providing monthly follow-up appointments for up
      to four months. The study tested the equivalence of the two forms of service
      delivery on a variety of outcome measures. RESULTS: Psychiatric consultation and
      follow-up delivered by telepsychiatry produced clinical outcomes that were
      equivalent to those achieved when the service was provided face to face. Patients
      in the two groups expressed similar levels of satisfaction with service. An
      analysis limited to the cost of providing the clinical service indicated that
      telepsychiatry was at least 10% less expensive per patient than service provided
      face to face. CONCLUSIONS: Psychiatric consultation and short-term follow-up can
      be as effective when delivered by telepsychiatry as when provided face to face.
      These findings do not necessarily mean that other types of mental health
      services, for example, various types of psychotherapy, are as effective when
      provided by telepsychiatry.

PMID- 17535946
TI  - Validity of electronically monitored medication adherence and conventional
      adherence measures in schizophrenia.
AB  - OBJECTIVE: This study evaluated the validity of prescriber, patient, and research
      assistant ratings of adherence to prescribed oral antipsychotic medication among
      outpatients with schizophrenia or schizoaffective disorder in comparison with
      electronic monitoring. METHODS: Adult outpatients with schizophrenia (N=35) or
      schizoaffective disorder (N=26) received adherence assessments via electronically
      monitored medication vial caps as well as by monthly prescriber, patient, and
      research assistant report for up to six months. RESULTS: Electronic monitoring
      detected greater nonadherence rates (57%) than either prescribers (7%) or
      patients (5%), though the research assistant ratings were 54%. No directional
      bias was found between electronic monitoring and assignment of adherence by
      research assistants, although disagreement occurred in 36% of cases. CONCLUSIONS:
      Both patients and prescribers grossly overestimated medication adherence, which
      may interfere with or reduce the effectiveness of diligent medication management.

PMID- 17535947
TI  - Quality of care in a Medicaid population with bipolar I disorder.
AB  - OBJECTIVE: This study examined whether presenting diagnosis and treatment in
      intensive settings (hospitalization, partial hospitalization, or residential
      programs) are correlated with the subsequent treatment of bipolar I disorder.
      METHODS: Claims data were studied retrospectively (fiscal years 1994-2000) for
      2,644 patients with bipolar I disorder who had been enrolled in Medicaid at least
      six months before their first observed bipolar diagnosis. Logistic regression
      models estimated the association between the presenting diagnosis and initial
      treatment setting and the subsequent treatment up to one year after the first
      observed bipolar diagnosis. Measures included receipt of guideline-recommended
      care (antimanic agent plus psychotherapy) or care discouraged by guidelines (an
      antidepressant without an antimanic agent). RESULTS: Only one-third of enrollees
      received both guideline-recommended treatments after the first observed bipolar
      diagnosis. Patients were less likely to receive both recommended treatments if
      the first observed mental health service occurred in an intensive setting.
      Enrollees presenting with a bipolar diagnosis were less likely to receive
      psychotherapy, whereas rates of antimanic medication use were similar to those
      with other presenting diagnoses. Presenting with depression or anxiety or other,
      nonbipolar diagnoses was associated with a higher likelihood of receiving
      pharmacotherapy discouraged by guidelines. CONCLUSIONS: This study raises general
      concerns for the treatment quality of bipolar I disorder in this medically
      complicated, largely disabled Medicaid population. Also, how bipolar I patients
      enter treatment can be associated with subsequent differences in treatment
      quality--information that can be useful to clinicians and policy makers when
      planning quality improvements to treatment programs.

PMID- 17535948
TI  - Treatment adherence with lithium and anticonvulsant medications among patients
      with bipolar disorder.
AB  - OBJECTIVE: Nonadherence limits the effectiveness of medications among patients
      with bipolar disorder. This study examined adherence with lithium and
      anticonvulsant medication among patients with bipolar disorder receiving
      treatment in Department of Veterans Affairs (VA) settings. METHODS: Patients
      receiving treatment in the VA for bipolar disorder during federal fiscal year
      2003 (FY03) and receiving lithium or anticonvulsant medication were identified
      (N=44,637) by using the VA's National Psychosis Registry. Medication adherence
      was assessed by using the medication possession ratio (MPR) for lithium,
      valproate or divalproex, carbamazepine, and lamotrigine. Patients were
      categorized into three groups: fully adherent (MPR greater than .80), partially
      adherent (MPR from more than .50 to .80), and nonadherent (MPR less than or equal
      to .50). RESULTS: A slight majority of individuals (54.1%) were fully adherent,
      24.5% were partially adherent, and 21.4% were nonadherent. Nonadherent
      individuals were more likely to be younger, unmarried, nonwhite, or homeless or
      to have diagnoses of a substance use disorder or fewer outpatient psychiatric
      visits in FY03. Adherence intensity was somewhat lower for valproate, compared
      with lithium or other anticonvulsants. Individuals given prescriptions for two
      agents to stabilize mood had better adherence than individuals given
      prescriptions for a single agent. Unexpectedly, in multivariate analyses
      adjusting for prior hospitalization, number of outpatient psychiatric visits, and
      a diagnosis of substance use disorder, poorer adherence was associated with
      decreased rates of hospitalization. CONCLUSIONS: Nearly one in two individuals
      given prescriptions for lithium or anticonvulsant medication to treat bipolar
      disorder did not take their medications as prescribed. The effectiveness of
      bipolar medication treatments is reduced by high rates of nonadherence in
      clinical settings.

PMID- 17535949
TI  - Using pharmacy data on partial adherence to inform clinical care of patients with
      serious mental illness.
AB  - OBJECTIVE: Low adherence to antipsychotic medications is a risk factor for poor
      outcomes for people with serious mental illness. Pharmacy data might be used by
      health systems to identify partially adherent patients for interventions. This
      study assessed whether using pharmacy data is an accurate screening method for
      identifying at-risk patients. METHODS: Administrative data were used to identify
      1,712 veterans as having schizophrenia or a schizoaffective or bipolar disorder
      and who had 12-month antipsychotic medication possession ratios (MPRs) of less
      than .80. Patients' charts were reviewed for alternative explanations for low
      rates of filling prescriptions for antipsychotic medication. RESULTS: Of 1,712
      patients whose pharmacy data indicated partial adherence (MPRs less than .80),
      17% (N=297) may have been adherent. Patients with bipolar disorder had higher
      odds of receiving a false-positive designation (adjusted odds ratio of 1.8, 95%
      confidence interval of 1.31-2.39). CONCLUSIONS: MPRs constructed from pharmacy
      data can be a useful first screen for identifying patients who need assistance
      with medication adherence.

PMID- 17535950
TI  - A comparative survey of missed initial and follow-up appointments to psychiatric
      specialties in the United kingdom.
AB  - OBJECTIVE: Missed appointments are common in psychiatry. Nonattendance at the
      initial appointment may have different prognostic significance than nonattendance
      at subsequent appointments. This study examined the frequency of missed
      appointments among 9,511 initial outpatient appointments and 7,700 follow-up
      appointments across ten psychiatric subspecialties in a publicly funded mental
      health service in the United Kingdom. RESULTS: The pooled missed appointment rate
      was 15.9%, higher than in previous studies on primary and secondary care
      attendance in the United Kingdom. Nonattendance was lowest on Fridays, in winter
      months, and in geriatric psychiatry and highest for substance abuse services and
      in community psychiatry. In most services, attendance improved after the initial
      appointment, but in psychosomatic medicine and geriatric psychiatry this pattern
      was reversed. CONCLUSIONS: There was a low rate of missed appointments in
      geriatric psychiatry, rehabilitation psychiatry, cognitive-behavioral therapy,
      and psychosocial medicine. A high nonattendance rate was found among persons with
      drug and alcohol difficulties and to a lesser extent in general adult psychiatry.
      Future studies should consider initial and follow-up appointments as distinct.

PMID- 17535951
TI  - Using telephone reminders to increase attendance at psychiatric appointments:
      findings of a pilot study in rural Appalachia.
AB  - OBJECTIVE: This study examined whether phone reminders increased attendance at
      intake and therapy appointments in an Appalachian community mental health center
      and whether it mattered who (therapist or staff) made the call. METHODS: One of
      three conditions (no reminder calls, therapist made calls, or staff made calls)
      was assigned to each week of the nine-week study. During the study period, 451
      appointments were scheduled (310 for therapy and 141 for intake). Mixed-effects
      logistic regression was used to analyze the data. RESULTS: Phone reminders were
      effective for intake appointments when therapists made direct contact with
      patients (43% for no contact and 94% for direct therapist contact). The other
      conditions did not significantly increase appointment keeping. As a result of
      these findings, therapists were asked to place reminder calls to patients
      scheduled for intake appointments for a ten-week period. Findings from the second
      pilot study replicated findings from the first, with direct contact resulting in
      significantly more kept appointments. CONCLUSIONS: Direct contact with therapists
      before initial appointments may increase appointment keeping by patients.

PMID- 17535952
TI  - CHADD and public attitudes about ADHD.

PMID- 17535953
TI  - Hispanics and telepsychiatry.

PMID- 17535954
TI  - "Consumer-directed care" and systems transformation.

PMID- 17535956
TI  - Reduction in postdischarge suicide in Sweden.

PMID- 17535958
TI  - And yet it moves: conformational States of the Ca2+ channel pore.

PMID- 17535959
TI  - Block of CaV1.2 channels by Gd3+ reveals preopening transitions in the
      selectivity filter.
AB  - Using the lanthanide gadolinium (Gd(3+)) as a Ca(2+) replacing probe, we
      investigated the voltage dependence of pore blockage of Ca(V)1.2 channels. Gd(+3)
      reduces peak currents (tonic block) and accelerates decay of ionic current during
      depolarization (use-dependent block). Because diffusion of Gd(3+) at
      concentrations used (<1 microM) is much slower than activation of the channel,
      the tonic effect is likely to be due to the blockage that occurred in closed
      channels before depolarization. We found that the dose-response curves for the
      two blocking effects of Gd(3+) shifted in parallel for Ba(2+), Sr(2+), and Ca(2+)
      currents through the wild-type channel, and for Ca(2+) currents through the
      selectivity filter mutation EEQE that lowers the blocking potency of Gd(3+). The
      correlation indicates that Gd(3+) binding to the same site causes both tonic and
      use-dependent blocking effects. The apparent on-rate for the tonic block
      increases with the prepulse voltage in the range -60 to -45 mV, where significant
      gating current but no ionic current occurs. When plotted together against
      voltage, the on-rates of tonic block (-100 to -45 mV) and of use-dependent block
      (-40 to 40 mV) fall on a single sigmoid that parallels the voltage dependence of
      the gating charge. The on-rate of tonic block by Gd(3+) decreases with
      concentration of Ba(2+), indicating that the apparent affinity of the site to
      permeant ions is about 1 mM in closed channels. Therefore, we propose that at
      submicromolar concentrations, Gd(3+) binds at the entry to the selectivity locus
      and that the affinity of the site for permeant ions decreases during preopening
      transitions of the channel.

PMID- 17535960
TI  - Ca2+-dependent inactivation of CaV1.2 channels prevents Gd3+ block: does Ca2+
      block the pore of inactivated channels?
AB  - Lanthanide gadolinium (Gd(3+)) blocks Ca(V)1.2 channels at the selectivity
      filter. Here we investigated whether Gd(3+) block interferes with Ca(2+)
      dependent inactivation, which requires Ca(2+) entry through the same site. Using
      brief pulses to 200 mV that relieve Gd(3+) block but not inactivation, we
      monitored how the proportions of open and open-blocked channels change during
      inactivation. We found that blocked channels inactivate much less. This is
      expected for Gd(3+) block of the Ca(2+) influx that enhances inactivation.
      However, we also found that the extent of Gd(3+) block did not change when
      inactivation was reduced by abolition of Ca(2+)/calmodulin interaction, showing
      that Gd(3+) does not block the inactivated channel. Thus, Gd(3+) block and
      inactivation are mutually exclusive, suggesting action at a common site. These
      observations suggest that inactivation causes a change at the selectivity filter
      that either hides the Gd(3+) site or reduces its affinity, or that Ca(2+)
      occupies the binding site at the selectivity filter in inactivated channels. The
      latter possibility is supported by previous findings that the EEQE mutation of
      the selectivity EEEE locus is void of Ca(2+)-dependent inactivation (Zong Z.Q.,
      J.Y. Zhou, and T. Tanabe. 1994. Biochem. Biophys. Res. Commun. 201:1117-11123),
      and that Ca(2+)-inactivated channels conduct Na(+) when Ca(2+) is removed from
      the extracellular medium (Babich O., D. Isaev, and R. Shirokov. 2005. J. Physiol.
      565:709-717). Based on these results, we propose that inactivation increases
      affinity of the selectivity filter for Ca(2+) so that Ca(2+) ion blocks the pore.
      A minimal model, in which the inactivation "gate" is an increase in affinity of
      the selectivity filter for permeating ions, successfully simulates the
      characteristic U-shaped voltage dependence of inactivation in Ca(2+).

PMID- 17535962
TI  - Aspartate-444 is essential for productive substrate interactions in a neuronal
      glutamate transporter.
AB  - In the central nervous system, electrogenic sodium- and potassium-coupled
      glutamate transporters terminate the synaptic actions of this neurotransmitter.
      In contrast to acidic amino acids, dicarboxylic acids are not recognized by
      glutamate transporters, but the related bacterial DctA transporters are capable
      of transporting succinate and other dicarboxylic acids. Transmembrane domain 8
      contains several residues that differ between these two types of transporters.
      One of these, aspartate-444 of the neuronal glutamate transporter EAAC1, is
      conserved in glutamate transporters, but a serine residue occupies this position
      in DctA transporters. When aspartate-444 is mutated to serine, cysteine, alanine,
      or even to glutamate, uptake of D-[(3)H]-aspartate as well as the inwardly
      rectifying steady-state currents induced by acidic amino acids is impaired. Even
      though succinate was not capable of inducing any steady-state transport currents,
      the dicarboxylic acid inhibited the sodium-dependent transient currents by the
      mutants with a neutral substitution at position 444. In the neutral substitution
      mutants inhibition of the transients was also observed with acidic amino acids.
      In the D444E mutant, acidic amino acids were potent inhibitors of the transient
      currents, whereas the apparent affinity for succinate was lower by at least three
      orders of magnitude. Even though L-aspartate could bind to D444E with a high
      apparent affinity, this binding resulted in inhibition rather than stimulation of
      the uncoupled anion conductance. Thus, a carboxylic acid-containing side chain at
      position 444 prevents the interaction of glutamate transporters with succinate,
      and the presence of aspartate itself at this position is crucial for productive
      substrate binding compatible with substrate translocation.

PMID- 17535961
TI  - Ca2+-secretion coupling is impaired in diabetic Goto Kakizaki rats.
AB  - The Goto Kakizaki (GK) rat is a widely used animal model to study defective
      glucose-stimulated insulin release in type-2 diabetes (T2D). As in T2D patients,
      the expression of several proteins involved in Ca(2+)-dependent exocytosis of
      insulin-containing large dense-core vesicles is dysregulated in this model. So
      far, a defect in late steps of insulin secretion could not be demonstrated. To
      resolve this apparent contradiction, we studied Ca(2+)-secretion coupling of
      healthy and GK rat beta cells in acute pancreatic tissue slices by assessing
      exocytosis with high time-resolution membrane capacitance measurements. We found
      that beta cells of GK rats respond to glucose stimulation with a normal increase
      in the cytosolic Ca(2+) concentration. During trains of depolarizing pulses, the
      secretory activity from GK rat beta cells was defective in spite of upregulated
      cell size and doubled voltage-activated Ca(2+) currents. In GK rat beta cells,
      evoked Ca(2+) entry was significantly less efficient in triggering release than
      in nondiabetic controls. This impairment was neither due to a decrease of
      functional vesicle pool sizes nor due to different kinetics of pool refilling.
      Strong stimulation with two successive trains of depolarizing pulses led to a
      prominent activity-dependent facilitation of release in GK rat beta cells,
      whereas secretion in controls was unaffected. Broad-spectrum inhibition of PKC
      sensitized Ca(2+)-dependent exocytosis, whereas it prevented the activity
      dependent facilitation in GK rat beta cells. We conclude that a decrease in the
      sensitivity of the GK rat beta-cell to depolarization-evoked Ca(2+) influx is
      involved in defective glucose-stimulated insulin secretion. Furthermore, we
      discuss a role for constitutively increased activity of one or more PKC
      isoenzymes in diabetic rat beta cells.

PMID- 17535963
TI  - An essential role for the SHIP2-dependent negative feedback loop in
      neuritogenesis of nerve growth factor-stimulated PC12 cells.
AB  - The local accumulation of phosphatidylinositol (3,4,5) trisphosphate (PIP(3)) and
      resulting activation of Rac1/Cdc42 play a critical role in nerve growth factor
      (NGF)-induced neurite outgrowth. To further explore the mechanism, we visualized
      PIP(3), phosphatidylinositol (3,4) bisphosphate, and Rac1/Cdc42 activities by
      fluorescence resonance energy transfer (FRET) imaging in NGF-stimulated PC12
      cells. Based on the obtained FRET images, and with the help of in silico kinetic
      reaction model, we predicted that PI-5-phosphatase negatively regulates PIP(3)
      upon NGF stimulation. In agreement with this model, depletion of Src homology 2
      domain-containing inositol polyphosphate 5-phosphatase 2 (SHIP2) markedly
      potentiated NGF-induced Rac1/Cdc42 activation and PIP(3) accumulation and
      considerably increased the number and the length of neurites in phosphate and
      tensin homologue-depleted PC12 cells. Further refinement of the computational
      model predicted Rac1 regulation of PI3-kinase and SHIP2, which was also validated
      experimentally. We propose that the SHIP2-mediated negative feedback on PIP(3)
      coordinately works with the PI3-kinase-mediated positive feedback to form an
      initial protrusive pattern and, later, to punctuate the PIP(3) accumulation to
      maintain proper neurite outgrowth.

PMID- 17535964
TI  - Regulation of connexin43 gap junctional communication by phosphatidylinositol 4,5
      bisphosphate.
AB  - Cell-cell communication through connexin43 (Cx43)-based gap junction channels is
      rapidly inhibited upon activation of various G protein-coupled receptors;
      however, the mechanism is unknown. We show that Cx43-based cell-cell
      communication is inhibited by depletion of phosphatidylinositol 4,5-bisphosphate
      (PtdIns[4,5]P(2)) from the plasma membrane. Knockdown of phospholipase Cbeta3
      (PLCbeta3) inhibits PtdIns(4,5)P(2) hydrolysis and keeps Cx43 channels open after
      receptor activation. Using a translocatable 5-phosphatase, we show that
      PtdIns(4,5)P(2) depletion is sufficient to close Cx43 channels. When
      PtdIns(4,5)P(2) is overproduced by PtdIns(4)P 5-kinase, Cx43 channel closure is
      impaired. We find that the Cx43 binding partner zona occludens 1 (ZO-1) interacts
      with PLCbeta3 via its third PDZ domain. ZO-1 is essential for PtdIns(4,5)P(2)
      hydrolyzing receptors to inhibit cell-cell communication, but not for receptor
      PLC coupling. Our results show that PtdIns(4,5)P(2) is a key regulator of Cx43
      channel function, with no role for other second messengers, and suggest that ZO-1
      assembles PLCbeta3 and Cx43 into a signaling complex to allow regulation of cell
      cell communication by localized changes in PtdIns(4,5)P(2).

PMID- 17535965
TI  - Ubiquitination differentially regulates clathrin-dependent internalization of
      protease-activated receptor-1.
AB  - Protease-activated receptor-1 (PAR1), a G protein-coupled receptor (GPCR) for
      thrombin, is irreversibly activated by proteolysis. Consequently, PAR1
      trafficking is critical for the fidelity of thrombin signaling. PAR1 displays
      constitutive and agonist-induced internalization, which are clathrin and dynamin
      dependent but are independent of arrestins. The clathrin adaptor AP2 (adaptor
      protein complex-2) is critical for constitutive but not for activated PAR1
      internalization. In this study, we show that ubiquitination negatively regulates
      PAR1 constitutive internalization and specifies a distinct clathrin adaptor
      requirement for activated receptor internalization. PAR1 is basally ubiquitinated
      and deubiquitinated after activation. A PAR1 lysineless mutant signaled normally
      but was not ubiquitinated. Constitutive internalization of ubiquitin (Ub)
      deficient PAR1 was markedly increased and inhibited by the fusion of Ub to the
      cytoplasmic tail. Ub-deficient PAR1 constitutive internalization was AP2
      dependent like the wild-type receptor. However, unlike wild-type PAR1, AP2 was
      required for the internalization of activated Ub-deficient receptor, suggesting
      that the internalization of ubiquitinated PAR1 requires different endocytic
      machinery. These studies reveal a novel function for ubiquitination in the
      regulation of GPCR internalization.

PMID- 17535966
TI  - Three-dimensional architecture of murine rod outer segments determined by
      cryoelectron tomography.
AB  - The rod outer segment (ROS) of photoreceptor cells houses all components
      necessary for phototransduction, a set of biochemical reactions that amplify and
      propagate a light signal. Theoretical approaches to quantify this process require
      precise information about the physical boundaries of the ROS. Dimensions of
      internal structures within the ROS of mammalian species have yet to be determined
      with the precision required for quantitative considerations. Cryoelectron
      tomography was utilized to obtain reliable three-dimensional morphological
      information about this important structure from murine retina. Vitrification of
      samples permitted imaging of the ROS in a minimally perturbed manner and the
      preservation of substructures. Tomograms revealed the characteristic highly
      organized arrangement of disc membranes stacked on top of one another with a
      surrounding plasma membrane. Distances among the various membrane components of
      the ROS were measured to define the space available for phototransduction to
      occur. Reconstruction of segments of the ROS from single-axis tilt series images
      provided a glimpse into the three-dimensional architecture of this highly
      differentiated neuron. The reconstructions revealed spacers that likely maintain
      the proper distance between adjacent discs and between discs and the plasma
      membrane. Spacers were found distributed throughout the discs, including regions
      that are distant from the rim region of discs.

PMID- 17535967
TI  - Essential role of PI3-kinase and phospholipase A2 in Dictyostelium discoideum
      chemotaxis.
AB  - Chemotaxis toward different cyclic adenosine monophosphate (cAMP) concentrations
      was tested in Dictyostelium discoideum cell lines with deletion of specific genes
      together with drugs to inhibit one or all combinations of the second-messenger
      systems PI3-kinase, phospholipase C (PLC), phospholipase A2 (PLA2), and cytosolic
      Ca(2+). The results show that inhibition of either PI3-kinase or PLA2 inhibits
      chemotaxis in shallow cAMP gradients, whereas both enzymes must be inhibited to
      prevent chemotaxis in steep cAMP gradients, suggesting that PI3-kinase and PLA2
      are two redundant mediators of chemotaxis. Mutant cells lacking PLC activity have
      normal chemotaxis; however, additional inhibition of PLA2 completely blocks
      chemotaxis, whereas inhibition of PI3-kinase has no effect, suggesting that all
      chemotaxis in plc-null cells is mediated by PLA2. Cells with deletion of the
      IP(3) receptor have the opposite phenotype: chemotaxis is completely dependent on
      PI3-kinase and insensitive to PLA2 inhibitors. This suggest that PI3-kinase
      mediated chemotaxis is regulated by PLC, probably through controlling PIP(2)
      levels and phosphatase and tensin homologue (PTEN) activity, whereas chemotaxis
      mediated by PLA2 appears to be controlled by intracellular Ca(2+).

PMID- 17535968
TI  - Building blood vessels--stem cell models in vascular biology.
AB  - Spheroids of differentiating embryonic stem cells, denoted embryoid bodies,
      constitute a high-quality model for vascular development, particularly well
      suited for loss-of-function analysis of genes required for early embryogenesis.
      This review examines vasculogenesis and angiogenesis in murine embryoid bodies
      and discusses the promise of stem cell-based models for the study of human
      vascular development.

PMID- 17535969
TI  - p38 MAPK-dependent shaping of the keratin cytoskeleton in cultured cells.
AB  - Plasticity of the resilient keratin intermediate filament cytoskeleton is an
      important prerequisite for epithelial tissue homeostasis. Here, the contribution
      of stress-activated p38 MAPK to keratin network organization was examined in
      cultured cells. It was observed that phosphorylated p38 colocalized with keratin
      granules that were rapidly formed in response to orthovanadate. The same p38(p)
      recruitment was noted during mitosis, in various stress situations and in cells
      producing mutant keratins. In all these situations keratin 8 became
      phosphorylated on S73, a well-known p38 target site. To demonstrate that p38
      dependent keratin phosphorylation determines keratin organization, p38 activity
      was pharmacologically and genetically modulated: up-regulation induced keratin
      granule formation, whereas down-regulation prevented keratin filament network
      disassembly. Furthermore, transient p38 inhibition also inhibited keratin
      filament precursor formation and mutant keratin granule dissolution.
      Collectively, the rapid and reversible effects of p38 activity on keratin
      phosphorylation and organization in diverse physiological, stress, and
      pathological situations identify p38-dependent signalling as a major intermediate
      filament-regulating pathway.

PMID- 17535970
TI  - DA-Raf1, a competent intrinsic dominant-negative antagonist of the Ras-ERK
      pathway, is required for myogenic differentiation.
AB  - Ras activates Raf, leading to the extracellular-regulated kinase (ERK)-mitogen
      activated protein kinase pathway, which is involved in a variety of cellular,
      physiological, and pathological responses. Thus, regulators of this Ras-Raf
      interaction play crucial roles in these responses. In this study, we report a
      novel regulator of the Ras-Raf interaction named DA-Raf1. DA-Raf1 is a splicing
      isoform of A-Raf with a wider tissue distribution than A-Raf. It contains the Ras
      binding domain but lacks the kinase domain, which is responsible for activation
      of the ERK pathway. As inferred from its structure, DA-Raf1 bound to activated
      Ras as well as M-Ras and interfered with the ERK pathway. The Ras-ERK pathway is
      essential for the negative regulation of myogenic differentiation induced by
      growth factors. DA-Raf1 served as a positive regulator of myogenic
      differentiation by inducing cell cycle arrest, the expression of myogenin and
      other muscle-specific proteins, and myotube formation. These results imply that
      DA-Raf1 is the first identified competent, intrinsic, dominant-negative
      antagonist of the Ras-ERK pathway.

PMID- 17535971
TI  - Immunization with vaccinia virus induces polyfunctional and phenotypically
      distinctive CD8(+) T cell responses.
AB  - Vaccinia virus immunization provides lifelong protection against smallpox, but
      the mechanisms of this exquisite protection are unknown. We used polychromatic
      flow cytometry to characterize the functional and phenotypic profile of CD8(+) T
      cells induced by vaccinia virus immunization in a comparative vaccine trial of
      modified vaccinia virus Ankara (MVA) versus Dryvax immunization in which
      protection was assessed against subsequent Dryvax challenge. Vaccinia virus
      specific CD8(+) T cells induced by both MVA and Dryvax were highly
      polyfunctional; they degranulated and produced interferon gamma, interleukin 2,
      macrophage inflammatory protein 1beta, and tumor necrosis factor alpha after
      antigenic stimulation. Responding CD8(+) T cells exhibited an unusual phenotype
      (CD45RO(-)CD27(intermediate)). The unique phenotype and high degree of
      polyfunctionality induced by vaccinia virus also extended to inserted HIV gene
      products of recombinant NYVAC. This quality of the CD8(+) T cell response may be
      at least partially responsible for the profound efficacy of these vaccines in
      protection against smallpox and serves as a benchmark against which other
      vaccines can be evaluated.

PMID- 17535972
TI  - DNA damage-induced cellular senescence is sufficient to suppress tumorigenesis: a
      mouse model.
AB  - Tumor suppressor p53-dependent apoptosis is critical in suppressing
      tumorigenesis. Previously, we reported that DNA double-strand breaks (DSBs) at
      the V(D)J recombination loci induced genomic instability in the developing
      lymphocytes of nonhomologous end-joining (NHEJ)-deficient, p53-deficient mice,
      which led to rapid lymphomagenesis. To test the ability of p53-dependent cell
      cycle arrest to suppress tumorigenesis in the absence of apoptosis in vivo, we
      crossbred NHEJ-deficient mice into a mutant p53R172P background; these mice have
      defects in apoptosis induction, but not cell cycle arrest. These double-mutant
      mice survived longer than NHEJ/p53 double-null mice and, remarkably, were
      completely tumor free. We detected accumulation of aberrant V(D)J recombination
      related DSBs at the T cell receptor (TCR) locus, and high expression levels of
      both mutant p53 and cell cycle checkpoint protein p21, but not the apoptotic
      protein p53-upregulated modulator of apoptosis. In addition, a substantial number
      of senescent cells were observed among both thymocytes and bone marrow cells.
      Cytogenetic studies revealed euploidy and limited chromosomal breaks in these
      lymphoid cells. The results indicate that precursor lymphocytes, which normally
      possess a high proliferation potential, are able to withdraw from the cell cycle
      and undergo senescence in response to the persistence of DSBs in a p53-p21
      dependent pathway; this is sufficient to inhibit oncogenic chromosomal
      abnormality and suppress tumorigenesis.

PMID- 17535973
TI  - Tumor suppressor p53 Arg72Pro polymorphism and longevity, cancer survival, and
      risk of cancer in the general population.
AB  - p53 is an important tumor suppressor, normally preventing cancer development via
      apoptosis. A genomic Arg72Pro substitution in the p53 protein has important
      influence on cell death via apoptosis, which could be beneficial. We therefore
      tested the hypotheses that this polymorphism influences longevity, survival after
      a cancer diagnosis, and risk of cancer in the general population. We examined a
      cohort of 9,219 participants ages 20-95 from the Danish general population with
      100% follow-up. The overall 12-yr survival was increased in p53 Arg/Pro
      heterozygotes with 3% (P = 0.003) and in Pro/Pro homozygotes with 6% (P = 0.002)
      versus Arg/Arg homozygotes, corresponding to an increase in median survival of 3
      yr for Pro/Pro versus Arg/Arg homozygotes. We also demonstrated an increased
      survival after the development of cancer, or even after the development of other
      life-threatening diseases, for Pro/Pro versus Arg/Arg homozygotes. The Arg72Pro
      substitution did not associate with decreased risk of cancer. In conclusion, in
      this large cohort from the general population, we show that a well-known
      functional single nucleotide polymorphism in the tumor suppressor p53 protein
      leads to increased longevity, but not to decreased risk of cancer. The increased
      longevity may be due to increased survival after a diagnosis of cancer or other
      life-threatening diseases.

PMID- 17535974
TI  - Distinct vascular endothelial growth factor signals for lymphatic vessel
      enlargement and sprouting.
AB  - Lymphatic vessel growth, or lymphangiogenesis, is regulated by vascular
      endothelial growth factor-C (VEGF-C) and -D via VEGF receptor 3 (VEGFR-3). Recent
      studies suggest that VEGF, which does not bind to VEGFR-3, can also induce
      lymphangiogenesis through unknown mechanisms. To dissect the receptor pathway
      that triggers VEGFR-3-independent lymphangiogenesis, we used both transgenic and
      adenoviral overexpression of placenta growth factor (PlGF) and VEGF-E, which are
      specific activators of VEGFR-1 and -2, respectively. Unlike PlGF, VEGF-E induced
      circumferential lymphatic vessel hyperplasia, but essentially no new vessel
      sprouting, when transduced into mouse skin via adenoviral vectors. This effect
      was not inhibited by blocking VEGF-C and -D. Postnatal lymphatic hyperplasia,
      without increased density of lymphatic vessels, was also detected in transgenic
      mice expressing VEGF-E in the skin, but not in mice expressing PlGF.
      Surprisingly, VEGF-E induced lymphatic hyperplasia postnatally, and it did not
      rescue the loss of lymphatic vessels in transgenic embryos where VEGF-C and VEGF
      D were blocked. Our data suggests that VEGFR-2 signals promote lymphatic vessel
      enlargement, but unlike in the blood vessels, are not involved in vessel
      sprouting to generate new lymphatic vessels in vivo.

PMID- 17535976
TI  - Apoptotic action of peroxisome proliferator-activated receptor-gamma activation
      in human non small-cell lung cancer is mediated via proline oxidase-induced
      reactive oxygen species formation.
AB  - Peroxisome proliferator-activated receptor (PPAR)-gamma ligands have been shown
      to inhibit human lung cancers by inducing apoptosis and differentiation. In the
      present study, we elucidated the apoptotic mechanism of PPARgamma activation in
      human lung cancers by using a novel PPARgamma agonist, 1-(trans-methylimino-N
      oxy)-6-(2-morpholinoethoxy)-3-phenyl-(1H-indene-2-carboxylic acid ethyl ester (KR
      62980), and rosiglitazone. PPARgamma activation selectively inhibited cell
      viability of non-small-cell lung cancer with little effect on small-cell lung
      cancer and normal lung cells. The cell death induced by PPARgamma activation
      presented apoptotic features of oligonucleosomal DNA fragmentation in A549 human
      non-small-cell lung cancer cell line. Reactive oxygen species (ROS) production
      was accompanied by increased expression of proline oxidase (POX), a redox enzyme
      expressed in mitochondria, upon incubation with the agonists. POX RNA
      interference treatment blocked PPARgamma-induced ROS formation and cytotoxicity,
      suggesting that POX plays a functional role in apoptosis through ROS formation.
      The apoptotic effects by the agonists were antagonized by bisphenol A diglycidyl
      ether, a PPARgamma antagonist, and by knockdown of PPARgamma expression,
      indicating the involvement of PPARgamma in these actions. The results of the
      present study suggest that PPARgamma activation induces apoptotic cell death in
      non-small-cell lung carcinoma mainly through ROS formation via POX induction.

PMID- 17535975
TI  - Tumoricidal activity of TLR7/8-activated inflammatory dendritic cells.
AB  - Imiquimod (IMQ), a synthetic agonist to Toll-like receptor (TLR) 7, is being
      successfully used for the treatment of certain skin neoplasms, but the exact
      mechanisms by which this compound induces tumor regression are not yet
      understood. While treating basal cell carcinoma (BCC) patients with topical IMQ,
      we detected, by immunohistochemistry, sizable numbers of both myeloid dendritic
      cells (mDCs) and plasmacytoid DCs (pDCs) within the inflammatory infiltrate.
      Surprisingly, peritumoral mDCs stained positive for perforin and granzyme B,
      whereas infiltrating pDCs expressed tumor necrosis factor-related apoptosis
      inducing ligand (TRAIL). The biological relevance of this observation can be
      deduced from our further findings that peripheral blood-derived CD11c(+) mDCs
      acquired antiperforin and anti-granzyme B reactivity upon TLR7/8 stimulation and
      could use these molecules to effectively lyse major histocompatibility complex
      (MHC) class I(lo) cancer cell lines. The same activation protocol led pDCs to
      kill MHC class I-bearing Jurkat cells in a TRAIL-dependent fashion. While
      suggesting that mDCs and pDCs are directly involved in the IMQ-induced
      destruction of BCC lesions, our data also add a new facet to the functional
      spectrum of DCs, ascribing to them a major role not only in the initiation but
      also in the effector phase of the immune response.

PMID- 17535977
TI  - The aryl hydrocarbon receptor sans xenobiotics: endogenous function in genetic
      model systems.
AB  - For more than 30 years, the aryl hydrocarbon receptor [Ah receptor (AHR)] has
      been extensively scrutinized as the cellular receptor for numerous environmental
      contaminants, including polychlorinated dioxins, dibenzofurans, and biphenyls.
      Recent evidence argues that this description is incomplete and perhaps myopic. Ah
      receptor orthologs have been demonstrated to mediate diverse endogenous functions
      in our close vertebrate relatives as well as our distant invertebrate ancestors.
      Moreover, these endogenous functions suggest that xenobiotic toxicity may be best
      understood in the context of intrinsic AHR physiology. In this literature review,
      we survey the emerging picture of endogenous AHR biology from work in the
      vertebrate and invertebrate model systems Mus musculus, Caenorhabditis elegans,
      and Drosophila melanogaster.

PMID- 17535978
TI  - Emergency medicine leads the way for training medical students in clinician-based
      ultrasound: a radical paradigm shift in patient imaging.

PMID- 17535979
TI  - Elder abuse: keeping the unthinkable in the differential.

PMID- 17535980
TI  - Commentary: Thoughtful practice and the older emergency department patient.

PMID- 17535981
TI  - Unexpected events during the intrahospital transport of critically ill patients.
AB  - OBJECTIVES: To examine unexpected events (UEs) that occur during the
      intrahospital transport of critically ill emergency department patients. METHODS:
      This was a prospective observational study of consecutive intrahospital
      transports between March 2003 and June 2004. The escorting emergency physician
      completed the data collection document either during or immediately after the
      transport. This document detailed equipment-related UEs, patient instability and
      invasive line-related UEs, whether the UEs required intervention, and whether the
      UEs were potentially life threatening (serious UEs). RESULTS: Of 339 transports
      observed, 230 (67.9%; 95% confidence interval [CI] = 62.6% to 72.7%) were
      associated with 604 UEs. Overall, there was a median of 1.0 UE per transport
      (range, 0-16). There were 277 (45.9%; 95% CI = 41.8% to 49.9%) UEs related to
      equipment, 158 (26.2%; 95% CI = 22.7% to 29.9%) related to patient instability,
      156 (25.8%; 95% CI = 22.4% to 29.6%) related to equipment lines, and 13 (2.2%,
      95% CI = 1.2% to 3.8%) miscellaneous UEs. The most common UEs were oxygen
      saturation probe failures, lead and line tangles, hypotension, and the wearing
      off of sedation and/or paralysis. Most UEs (478 [79.1%]; 95% CI = 75.6% to 82.3%)
      required an intervention. Emergency physicians had a significantly lower UE rate
      than residents. Thirty serious UEs occurred; 5.0% (95% CI = 3.4% to 7.1%) of UEs
      and 8.9% (95% CI = 6.2% to 12.5%) of transports were associated with a serious
      UE. The most common were severe hypotension, decreasing consciousness requiring
      intubation, and increased intracranial pressure. CONCLUSIONS: Unexpected events
      during the intrahospital transport of critically ill patients from the emergency
      department are common and can be potentially life threatening. Transporting
      physician experience is associated with UE rate. Strict adherence to and review
      of existing transport guidelines is recommended.

PMID- 17535982
TI  - Integrating the core competencies: proceedings from the 2005 Academic Assembly
      Consortium.

PMID- 17535983
TI  - Crystal-induced neutrophil activation. IX. Syk-dependent activation of class Ia
      phosphatidylinositol 3-kinase.
AB  - The deposition of monosodium urate (MSU) crystals in the joints of humans leads
      to an extremely acute, inflammatory reaction, commonly known as gout,
      characterized by a massive infiltration of neutrophils. Direct interactions of
      MSU crystals with human neutrophils and inflammatory mediators are crucial to the
      induction and perpetuation of gout attacks. The intracellular signaling events
      initiated by the physical interaction between MSU crystals and neutrophils depend
      on the activation of specific tyrosine kinases (Src and Syk, in particular). In
      addition, PI-3Ks may be involved. The present study investigates the involvement
      of the PI-3K family in the mediation of the responses of human neutrophils to MSU
      crystals. The results obtained indicate that the interaction of MSU crystals with
      human neutrophils leads to the stimulation of class Ia PI-3Ks by a mechanism that
      is dependent on the tyrosine kinase Syk. We also found an increase in the amount
      of p85 associated with the Nonidet P-40-insoluble fraction derived from MSU
      crystal-stimulated human neutrophils. Furthermore, MSU crystals induce the
      formation of a complex containing p85 and Syk, which is mediated by the Src
      family kinases. Finally, evidence is also obtained indicating that the activation
      of PI-3Ks by MSU crystals is a critical element regulating phospholipase D
      activation and degranulation of human neutrophils. The latter response is likely
      to be involved in the joint and tissue damage that occurs in gouty patients.

PMID- 17535984
TI  - Expression and translocation of fluorescent-tagged p21-activated kinase-binding
      domain and PH domain of protein kinase B during murine neutrophil chemotaxis.
AB  - Neutrophils are key cells of the innate immune system; they are terminally
      differentiated and therefore difficult to genetically manipulate and study in
      vitro. In the present study, we describe a protocol to transiently express two
      fluorescent markers, the PH domain of protein kinase B fused to red fluorescent
      protein and the p21-activated kinase-binding domain fused to a yellow fluorescent
      protein, in primary neutrophils. Using this approach, we are able to achieve a
      transfection efficiency of approximately 30%. The expression of the transfected
      probes occurred within 2 h and allowed for real-time monitoring of intermediates
      in key neutrophil activation pathways at the leading edge of migrating cells. We
      describe here a transfection protocol for primary neutrophils, which preserves
      fMLP-mediated cell polarization and cytoskeleton reorganization with simultaneous
      accumulation of PI-3K products and active Rac at the leading edge. The
      visualization and analysis of transfected fluorescent markers in primary
      neutrophils are a powerful technique to monitor chemotaxis signaling pathways in
      real time.

PMID- 17535985
TI  - Maternal vitamin D deficiency increases the risk of preeclampsia.
AB  - CONTEXT: Vitamin D has direct influence on molecular pathways proposed to be
      important in the pathogenesis of preeclampsia, yet the vitamin D-preeclampsia
      relation has not been studied. OBJECTIVES: We aimed to assess the effect of
      maternal 25-hydroxyvitamin D [25(OH)D] concentration on the risk of preeclampsia
      and to assess the vitamin D status of newborns of preeclamptic mothers. DESIGN
      AND SETTING: We conducted a nested case-control study of pregnant women followed
      from less than 16 wk gestation to delivery (1997-2001) at prenatal clinics and
      private practices. PATIENTS: Patients included nulliparous pregnant women with
      singleton pregnancies who developed preeclampsia (n = 55) or did not develop
      preeclampsia (n = 219). Women's banked sera were newly measured for 25(OH)D. MAIN
      OUTCOME MEASURE: The main outcome measure was preeclampsia (new-onset gestational
      hypertension and proteinuria for the first time after 20 wk gestation). Our
      hypotheses were formulated before data collection. RESULTS: Adjusted serum
      25(OH)D concentrations in early pregnancy were lower in women who subsequently
      developed preeclampsia compared with controls [geometric mean, 45.4 nmol/liter,
      and 95% confidence interval (CI), 38.6-53.4 nmol/liter, vs. 53.1 and 47.1-59.9
      nmol/liter; P < 0.01]. There was a monotonic dose-response relation between serum
      25(OH)D concentrations at less than 22 wk and risk of preeclampsia. After
      confounder adjustment, a 50-nmol/liter decline in 25(OH)D concentration doubled
      the risk of preeclampsia (adjusted odds ratio, 2.4; 95% CI, 1.1-5.4). Newborns of
      preeclamptic mothers were twice as likely as control newborns to have 25(OH)D
      less than 37.5 nmol/liter (adjusted odds ratio, 2.2; 95% CI, 1.2-4.1).
      CONCLUSIONS: Maternal vitamin D deficiency may be an independent risk factor for
      preeclampsia. Vitamin D supplementation in early pregnancy should be explored for
      preventing preeclampsia and promoting neonatal well-being.

PMID- 17535986
TI  - Heritability of plasma adiponectin levels and body mass index in twins.
AB  - CONTEXT: Adiponectin is suspected to exert antiatherogenic, antiinflammatory, and
      insulin-sensitizing effects. However, the relative importance of the genetic and
      environmental factors in influencing plasma adiponectin levels (ADPN) remains
      unclear. OBJECTIVE: The aim of the study was to investigate whether ADPN and body
      mass index (BMI) are genetically determined. DESIGN, SETTING, PARTICIPANTS, AND
      MAIN OUTCOME MEASURES: In a series of 60 pairs of healthy twins, we estimated
      genetic variance and heritability of ADPN and BMI using both ANOVA and path
      analysis methods. Twins were genotyped at two biallelic single nucleotide
      polymorphisms (SNPs) at the gene encoding adiponectin: the +45 T/G (on exon 2)
      and the -11377 G/C (on the promoter). RESULTS: A total of 30 pairs of twins were
      Monozygotic (MZ), and 30 were dizygotic (DZ). The mean ADPN (+/-SD) was 10.6 +/-
      5.7 in MZ and 11.1 +/- 4.5 in DZ twins (nonsignificant). Three tests of
      heritability (within pair = 1.13, P < 0.0001; among components = 1.62, P = 0.005;
      and intraclass correlation 1.34, P < 0.0001) consistently showed ADPN
      heritability. The preferred model of a likelihood-based analysis included an
      additive genetic influence and an individually unique environmental influence for
      ADPN, accounting for 88% and 12% of ADPN variance, respectively. We found a
      significantly higher within-pair difference of ADPN in DZ than in MZ pairs, and
      in +45 T/G SNP discordant compared with concordant DZ twins, indicating a
      significant effect of this adiponectin gene SNP on ADPN. CONCLUSIONS: ADPN shows
      significant genetic variance and heritability, which is independent of BMI and
      partly accounted for by the +45 T/G, but not the -11377 G/C adiponectin gene SNP.

PMID- 17535987
TI  - Genomic polymorphism at the interferon-induced helicase (IFIH1) locus contributes
      to Graves' disease susceptibility.
AB  - CONTEXT: A recent large-scale analysis of nonsynonymous coding polymorphisms
      showed strong evidence that an alanine to threonine amino acid change at codon
      946 of the interferon-induced helicase (IFIH1) gene (SNP ID rs1990760) was
      associated with type 1 diabetes. Previous investigations have also demonstrated
      that an intronic polymorphism (termed PD1.3; SNP ID rs11568821) in the programmed
      cell death (PDCD1) gene was associated with systemic lupus erythematosus and
      rheumatoid arthritis. OBJECTIVE: We sought to replicate these genetic
      associations in Graves' disease and autoimmune Addison's disease patient cohorts.
      PATIENTS AND METHODS: A total of 602 Graves' disease subjects, 214 Addison's
      disease subjects, and 446 healthy controls were genotyped for the IFIH1 and PDCD1
      single-nucleotide polymorphisms using mass spectrometer analysis of primer
      extension products (Sequenom). RESULTS: The alanine-carrying allele at the IFIH1
      codon 946 polymorphism was present in 796 of 1204 (66%) Graves' disease patient
      alleles compared with 508 of 892 (57%) control subject alleles [odds ratio 1.47
      (5-95% confidence interval, 1.23-1.76); P = 1.9 x 10(-5)]. In contrast, there was
      no association of alleles at this marker in autoimmune Addison's disease. Neither
      was there evidence for association in either patient cohort at the PD1.3
      polymorphism. CONCLUSIONS: We confirm a significant contribution of the Ala946Thr
      IFIH1 polymorphism to organ-specific autoimmune diseases, extending the range of
      conditions associated with this variant to include Graves' disease. This
      polymorphism may also contribute to several other autoimmune disorders.

PMID- 17535988
TI  - Lower levels of urinary 2-hydroxyestrogens in polycystic ovary syndrome.
AB  - CONTEXT: Women with polycystic ovary syndrome (PCOS) have anovulation due to
      arrested follicular maturation. The substrate (2-hydroxyestrogen) and product (2
      methoxyestrogen) of catechol-O-methyl transferase (COMT) have been shown to
      modulate proliferation and angiogenesis of granulosa cells. OBJECTIVE: The
      objective of the study was to evaluate COMT ovarian expression as well as the
      production of estrogen metabolites (2-hydroxyestrogen and 2-methoxyestrogen) in
      subjects with PCOS. DESIGN: Immunohistochemistry was used to assess COMT
      expression in ovarian tissues. Urinary levels of 10 different estrogens and
      estrogen metabolites were measured using enzyme-labeled immunoassays and/or
      liquid chromatography with tandem mass spectrometry. SETTING: The study was
      conducted at a tertiary university referral center. PATIENTS AND OTHER
      PARTICIPANTS: Ovarian tissues were obtained from six control subjects and six
      subjects with PCOS. Fasting first-void urinary samples were collected from 49
      subjects with PCOS and 36 healthy control subjects. MAIN OUTCOME MEASURE(S): COMT
      protein expression in ovarian tissues was measured. Urinary levels of 2
      hydroxyestrogen and 2-methoxyestrogen levels in PCOS patients were also measured.
      RESULTS: Whereas immunohistochemistry showed that COMT was expressed in ovaries
      from control and PCOS subjects, its expression was significantly higher in
      ovaries from subjects with PCOS, in both the follicular structures and ovarian
      stroma. The urinary 2-hydroxyestrogen level was significantly lower in subjects
      with PCOS, compared with normal controls (P = 0.009). Additionally, urinary 2
      hydroxyestrogen levels negatively correlated with serum insulin levels in
      subjects with PCOS (r = -0.333, P =0 .031). CONCLUSIONS: Urinary 2
      hydroxyestrogen is decreased in subjects with PCOS, which could be due in part to
      increased ovarian expression of COMT. Further studies are needed to ascertain the
      role of estrogen metabolism in PCOS before this information can be used in
      clinical settings.

PMID- 17535989
TI  - Genetics of carney triad: recurrent losses at chromosome 1 but lack of germline
      mutations in genes associated with paragangliomas and gastrointestinal stromal
      tumors.
AB  - CONTEXT: Carney triad (CT) describes the association of paragangliomas (PGLs)
      with gastrointestinal stromal tumors (GISTs) and pulmonary chondromas.
      Inactivating mutations of the mitochondrial complex II succinate dehydrogenase
      (SDH) enzyme subunits SDHB, SDHC, and SDHD are found in PGLs, gain-of-function
      mutations of c-kit (KIT), and platelet-derived growth factor receptor A (PDGFRA)
      in GISTs. OBJECTIVE: Our objective was to investigate the possibility that
      patients with CT and/or their tumors may harbor mutations of the SDHB, SDHC,
      SDHD, KIT, and PDGFRA genes and identify any other genetic alterations in CT
      tumors. DESIGN: Three males and 34 females with CT were studied retrospectively.
      We sequenced the stated genes and performed comparative genomic hybridization on
      a total of 41 tumors. RESULTS: No patient had coding sequence mutations of the
      investigated genes. Comparative genomic hybridization revealed a number of DNA
      copy number changes: losses dominated among benign lesions, there were an equal
      number of gains and losses in malignant lesions, and the average number of
      alterations in malignant tumors was higher compared with benign lesions. The most
      frequent and greatest contiguous change was 1q12-q21 deletion, a region that
      harbors the SDHC gene. Another frequent change was loss of 1p. Allelic losses of
      1p and 1q were confirmed by fluorescent in situ hybridization and loss-of
      heterozygosity studies. CONCLUSIONS: We conclude that CT is not due to SDH
      inactivating or KIT- and PDGFRA-activating mutations. GISTs and PGLs in CT are
      associated with chromosome 1 and other changes that appear to participate in
      tumor progression and point to their common genetic cause.

PMID- 17535990
TI  - Reduced sun exposure does not explain the inverse association of 25
      hydroxyvitamin D with percent body fat in older adults.
AB  - CONTEXT: Greater adiposity is associated with lower blood levels of 25
      hydroxyvitamin D [25(OH)D]. The extent to which this results from reduced sun
      exposure among heavier individuals is unknown. OBJECTIVES: This analysis was
      conducted to determine whether sun exposure habits differ according to percent
      body fat (%FAT) in older adults and to what extent they explain the inverse
      association of adiposity with 25(OH)D in that population. DESIGN: We performed a
      cross-sectional analysis of baseline data from a randomized trial of calcium and
      vitamin D supplementation to prevent bone loss. SETTING: The study was performed
      at the Metabolic Research Unit at the Jean Mayer United States Department of
      Agriculture Human Nutrition Research Center on Aging at Tufts University.
      PARTICIPANTS: A total of 381 generally healthy male and female volunteers age 65
      and older participated in the study. Exclusion criteria included vitamin D and
      calcium supplement use, and medical conditions and medications known to affect
      bone metabolism. INTERVENTION: There were no interventions. Measurements for this
      analysis were made before participants received trial supplements. MAIN OUTCOME
      MEASURES: Plasma 25(OH)D, an indicator of vitamin D status, was measured.
      RESULTS: Sunscreen use, hours spent outside per week, and percent of skin exposed
      did not differ across quartiles of %FAT (P > 0.43). 25(OH)D decreased across %FAT
      quartiles (P < 0.05) and was about 20% lower in the highest compared with the
      lowest quartile of %FAT after adjustments for age, sex, season, and vitamin D
      intake. Further adjustment for sun exposure habits had little effect on estimates
      of 25(OH)D. CONCLUSIONS: In older adults, sun exposure habits do not vary
      according to adiposity and do not appear to explain lower 25(OH)D concentrations
      with increasing adiposity.

PMID- 17535991
TI  - Detailed analysis of variation at and around mitochondrial position 16189 in a
      large Finnish cohort reveals no significant associations with early growth or
      metabolic phenotypes at age 31 years.
AB  - CONTEXT: Mitochondrial dysfunction is increasingly implicated in pathogenesis of
      adult metabolic disease. Rare mitochondrial (mt) DNA mutations impair glucose
      homeostasis, but the contribution of common variants is unclear. In small
      studies, variation within the OriB origin of replication (at mt16189 in
      particular) has been associated with both early growth and adult metabolic
      phenotypes and may contribute to life-course relationships between the two.
      OBJECTIVE: The aim was to study a large well-characterized cohort to determine
      whether previously reported small-scale associations between OriB sequence
      variation and early growth and adult metabolic phenotypes are robust.
      DESIGN/SETTING/PARTICIPANTS: This was a genetic association study of 5470
      individuals from the population-based Northern Finland Birth Cohort of 1966,
      followed prospectively from pregnancy to age 31 yr. MAIN OUTCOME MEASURES: We
      measured indices of early growth (including birth weight, placental weight, and
      ponderal index) and adult metabolic homeostasis (including body mass index,
      fasting glucose and insulin, indices of insulin action and secretion) and their
      relationship to variation in the OriB region. RESULTS: Previously reported
      associations could not be confirmed. There were no significant (P < 0.01,
      uncorrected) associations between OriB sequence variation and measures of early
      growth including birth weight (P = 0.52, comparing individuals with mt16189T to
      those with a homopolymeric C-tract) and placental weight (P = 0.49). There were
      no significant associations with adult metabolic phenotypes including fasting
      glucose (P = 0.07), fasting insulin (P = 0.42), and homeostatic model assessment
      derived measures of insulin sensitivity or secretion (P = 0.45 and P = 0.56,
      respectively). CONCLUSION: Despite substantial power to detect previously
      reported effects, mtDNA variations around OriB are not major contributors to
      variation in early growth and metabolic phenotypes during early adulthood.

PMID- 17535992
TI  - Molecular evidence for a link between the N363S glucocorticoid receptor
      polymorphism and altered gene expression.
AB  - CONTEXT: A single-nucleotide polymorphism (SNP) in the human glucocorticoid
      receptor (hGR) N363S (rs6195) has been the focus of several clinical studies, and
      some epidemiological data link this SNP to increased glucocorticoid sensitivity,
      coronary artery disease, and increased body mass index. However, molecular
      studies in vitro using reporter gene expression systems have failed, for the most
      part, to define a link between this polymorphism and altered glucocorticoid
      receptor function. OBJECTIVE: The objective of this study was to address the
      biological relevancy of N363S SNP in GR function by establishing stable U-2 OS
      (human osteosarcoma) cell lines expressing wild-type hGR or N363S and examining
      these receptors under a variety of conditions that probe for GR activity
      including human gene microarray analysis. DESIGN: Functional assays with reporter
      gene systems, Western blotting, and human microarray analysis were used to
      evaluate the activity of wild-type and N363S GR in both transiently and stably
      expressing cells. In addition, quantitative RT-PCR was used to confirm the
      microarray analysis. RESULTS: Functional assays with reporter gene systems and
      homologous down-regulation revealed only minor differences between the wild-type
      hGR and N363S receptors in both transiently and stably expressing cell lines.
      However, examination of the two receptors by human gene microarray analysis
      revealed a unique gene expression profile for N363S. CONCLUSIONS: These studies
      demonstrate that the N363S SNP regulates a novel set of genes with several of the
      regulated genes supporting a potential role for this GR polymorphism in human
      diseases.

PMID- 17535993
TI  - Elastography: new developments in ultrasound for predicting malignancy in thyroid
      nodules.
AB  - BACKGROUND: Elastography is a newly developed dynamic technique that uses
      ultrasound (US) to provide an estimation of tissue stiffness by measuring the
      degree of distortion under the application of an external force. US elastography
      has been applied to differentiate malignant from benign lesions. PATIENTS: This
      study included 92 consecutive patients with a single thyroid nodule who underwent
      surgery for compressive symptoms or suspicion of malignancy on fine needle
      aspiration cytology. Tissue stiffness on US elastography was scored from one
      (greatest elastic strain) to five (no strain). RESULTS: On US elastography:
      scores 1 and 2 were found in 49 cases, all benign lesions; score 3 in 13 cases,
      one carcinoma and 12 benign lesions; and scores 4 and 5 in 30 cases, all
      carcinomas. Thus, the elasticity scores 4-5 were highly predictive of malignancy
      (P < 0.0001), with a sensitivity of 97%, a specificity of 100%, a positive
      predictive value of 100%, and a negative predictive value of 98%. In 32 patients
      with an indeterminate fine needle aspiration result, the conventional US was not
      predictive of malignancy, while an US elastographic score of 4-5 was observed in
      six of seven (86%) patients with carcinoma on histology, and a score of 1-3 in
      all 25 patients with benign lesions. CONCLUSIONS: US elastography has great
      potential as an adjunctive tool for the diagnosis of thyroid cancer, especially
      in indeterminate nodules on cytology. Larger prospective studies are needed to
      confirm these results and establish the diagnostic accuracy of this new
      technique.

PMID- 17535994
TI  - The heterogeneous distribution of BRAF mutation supports the independent clonal
      origin of distinct tumor foci in multifocal papillary thyroid carcinoma.
AB  - CONTEXT: Papillary thyroid carcinoma (PTC) is frequently multifocal. Independent
      PTC foci may occur either from intraglandular metastases from a single dominant
      tumor or as unrelated neoplastic clones. In rare cases, the simultaneous presence
      of PTC foci of different histopathological subtypes points to independent sites
      of tumor formation. OBJECTIVES: We examined the pattern of BRAF mutations in
      noncontiguous tumor foci and node metastases from 69 patients affected by
      multicentric PTC. These included 19 cases characterized by the simultaneous
      presence of different PTC histopathological variants. DESIGN: BRAF (exon 15)
      mutation was examined by PCR-single strand conformational polymorphism followed
      by DNA sequencing in laser-capture microdissected tissue samples. RESULTS:
      Discordant patterns of BRAF mutation were found in about 40% of the multifocal
      PTCs. In node metastases, BRAF mutations were, in most but not all the cases,
      concordant with the dominant tumor. A discordant pattern of BRAF mutation was
      also found in about 50% of the cases in which multiple foci of different
      histopathological variants were present. CONCLUSIONS: The heterogeneous
      distribution of BRAF mutations suggests that discrete tumor foci in multifocal
      PTC may occur as independent tumors. This information has to be considered in the
      design of targeted therapeutic approaches with BRAF pathway inhibitors.

PMID- 17535995
TI  - Growth hormone increases final height in patients with juvenile idiopathic
      arthritis: data from a randomized controlled study.
AB  - BACKGROUND: GH treatment stimulates growth in short children with juvenile
      idiopathic arthritis (JIA). The extent to which this therapy increases final
      height is not known. METHODS: Thirty-one growth-retarded children with systemic
      and polyarticular idiopathic arthritis were enrolled in this controlled study.
      After a mean observational time of 8.4 yr, final height was reached in 13
      patients (seven females and six males) treated with GH for a mean of 6.7 yr in a
      dose of 0.33 mg/kg body weight per week. Eighteen patients (12 females and six
      males) served as an untreated control group. RESULTS: Mean increment in height in
      the treatment group was 1.6 +/- 0.8 SD, whereas the patients of the control group
      lost 0.7 +/- 1.8 SD. Overall, mean final height in the treatment group was -1.6
      SD and in the control group -3.4 SD. More GH-treated patients reached a final
      height within target height than untreated patients (11 of 13 vs. four of 18).
      Disease activity markers had a significant influence on height outcome. After
      adjustment for baseline and average disease activity, the difference between
      treatment and control group was still significant (mean 1.5 SD). Patients with a
      moderate overall disease activity profited most from GH treatment. No adverse
      events were noted throughout the study. CONCLUSION: Our data suggest that long
      term GH therapy has a beneficial effect on growth and final height in the
      majority of growth retarded children with severe forms of JIA.

PMID- 17535996
TI  - Patients with classic congenital adrenal hyperplasia have decreased epinephrine
      reserve and defective glycemic control during prolonged moderate-intensity
      exercise.
AB  - CONTEXT: Patients with classic congenital adrenal hyperplasia (CAH) have
      adrenomedullary dysplasia and hypofunction, and their lack of adrenomedullary
      reserve has been associated with a defective glucose response to brief high
      intensity exercise. OBJECTIVE: Our objective was to assess hormonal, metabolic,
      and cardiovascular response to prolonged moderate-intensity exercise comparable
      to brisk walking in adolescents with classic CAH. SUBJECTS AND METHODS: We
      compared six adolescents with classic CAH (16-20 yr old) with seven age-, sex-,
      and body mass index group-matched controls (16-23 yr old) using a 90-min
      standardized ergometer test. Metabolic, hormonal, and cardiovascular parameters
      were studied during exercise and recovery. RESULTS: Glucose did not change
      throughout exercise and recovery for controls, whereas CAH patients showed a
      steady decline in glucose during exercise with an increase in glucose in the
      postexercise period. Glucose levels were significantly lower in CAH patients at
      60 (P = 0.04), 75 (P = 0.01), and 90 (P = 0.03) min of exercise and 15 (P = 0.02)
      min post exercise, whereas glucose levels were comparable between the two groups
      early in exercise and at 30 min (P = 0.19) post exercise. As compared with
      controls, CAH patients had significantly lower epinephrine (P = 0.002) and
      cortisol (P < or = 0.001) levels throughout the study and similar norepinephrine,
      glucagon, and GH levels. Patients with CAH and controls had comparable
      cardiovascular parameters and perceived level of exertion. Despite having lower
      glucose levels, insulin levels were slightly higher in CAH patients during the
      testing period (P = 0.17), suggesting insulin insensitivity. CONCLUSION: CAH
      patients have defective glycemic control and altered metabolic and hormonal
      responses during prolonged moderate-intensity exercise comparable to brisk
      walking.

PMID- 17535997
TI  - Surgery or surveillance for mild asymptomatic primary hyperparathyroidism: a
      prospective, randomized clinical trial.
AB  - CONTEXT: It is unclear whether patients with asymptomatic primary
      hyperparathyroidism (PHPT) do better with parathyroidectomy (PTx) as compared
      with conservative medical management. OBJECTIVE: The aim of the study was to
      evaluate the beneficial effect of PTx vs. conservative management in patients
      with mild asymptomatic PHPT. DESIGN: We conducted a prospective, randomized
      study. SETTING: The study took place at a referral center. PATIENTS: We studied
      50 patients who did not meet any guidelines for parathyroid surgery as
      recommended by the National Institutes of Health Consensus Development Conference
      on Asymptomatic PHPT. INTERVENTION: Patients were randomly assigned to PTx or no
      PTx and were evaluated at 6 months and at 1 yr. MAIN OUTCOME MEASURES: We
      compared changes (percentage of basal) of lumbar spine bone mineral density (BMD)
      between the two groups at 1 yr. RESULTS: The change in BMD at lumbar spine was
      greater after PTx (+4.16 +/- 1.13 for PTx vs. -1.12 +/- 0.71 for no PTx; P =
      0.0002). The change in BMD at the total hip was also significantly greater in the
      PTx group (+2.61 +/- 0.71 for PTx vs. -1.88 +/- 0.60 for no PTx; P = 0.0001).
      There was no difference in BMD after 1 yr between both groups at the one-third
      radius site. In comparison with those who did not undergo surgery, the PTx
      subjects, after 1 yr, showed significant differences in four quality of life
      measures as determined by the 36-item short form health survey scale: bodily pain
      (P = 0.001), general health (P = 0.008), vitality (P = 0.003), and mental health
      (P = 0.017). CONCLUSIONS: In patients with mild asymptomatic PHPT, successful PTx
      is followed by an improvement in BMD and quality of life. Most patients followed
      without surgery did not show evidence of progression.

PMID- 17535998
TI  - Measurement of salivary cortisol concentration in the assessment of adrenal
      function in critically ill subjects: a surrogate marker of the circulating free
      cortisol.
AB  - METHODS: Baseline and cosyntropin-stimulated serum (total and free) and salivary
      cortisol concentrations were measured, in the early afternoon, in 51 critically
      ill patients and healthy subjects. Patients were stratified according to their
      serum albumin at the time of testing: those whose serum albumin levels were 2.5
      gm/dl or less vs. others whose levels were greater than 2.5 gm/dl. RESULTS:
      Baseline and cosyntropin-stimulated serum free cortisol levels were similar in
      the two groups of critically ill patients and were severalfold higher (P < 0.001)
      than those of healthy subjects. Similarly, baseline and cosyntropin-stimulated
      salivary cortisol concentrations were equally elevated in the two critically ill
      patient groups and were severalfold higher (P < 0.001) than those of healthy
      subjects. Salivary cortisol concentrations correlated well with the measured
      serum free cortisol levels. CONCLUSIONS: Salivary cortisol measurements are
      simple to obtain, easy to measure in most laboratories, and provide an indirect
      yet reliable and practical assessment of the serum free cortisol concentrations
      during critical illnesses. The concentrations of the two measures of unbound
      cortisol determined in two different body fluids correlated very well, regardless
      of the serum protein concentrations. Measurements of salivary cortisol can serve
      as a surrogate marker for the free cortisol in the circulation.

PMID- 17535999
TI  - Ghrelin affects the release of luteolytic and luteotropic factors in human luteal
      cells.
AB  - CONTEXT: Ghrelin, well-known modulator of food intake and energy balance, is a
      rather ubiquitous peptide involved in several endocrine and nonendocrine actions.
      A possible as-yet-unknown role for ghrelin in modulating luteal function has been
      suggested because both ghrelin and its receptor (GRLN-R) have been
      immunohistochemically detected in human corpus luteum. OBJECTIVE: We first
      investigated GRLN-R mRNA expression in midluteal phase human luteal cells.
      Ghrelin effect on basal and human chorionic gonadotropin (hCG)-stimulated
      progesterone (P) release was then analyzed. Finally, we investigated whether
      ghrelin could affect luteal release of vascular endothelial growth factor (VEGF),
      prostaglandin (PG) E(2), both luteotropic factors, and PGF(2alpha), luteolytic
      modulator. Ghrelin effect on both basal and hypoxia-stimulated VEGF luteal
      expression was analyzed. METHODS: Human luteal cells were incubated for 24 h with
      ghrelin (10(-13) to 10(-7) m) or hCG (100 ng/ml) or CoCl(2) (10 microm), chemical
      hypoxia, or with hCG or CoCl(2) in combination with ghrelin. Both GRLN-R mRNA and
      VEGF mRNA were evaluated by real-time RT-PCR. PGs and P release was assayed by
      RIA, whereas VEGF release by ELISA. RESULTS: GRLN-R mRNA expression was
      demonstrated in human luteal cells. Both basal and hCG-stimulated P release was
      significantly decreased by ghrelin, which was able to reduce PGE(2) and increase
      PGF(2alpha) luteal release. Both basal and hypoxia-stimulated VEGF release was
      significantly decreased by ghrelin, which did not affect VEGF mRNA luteal
      expression. CONCLUSIONS: The present in vitro study provides the first evidence
      of a direct inhibitory influence of ghrelin on human luteal function.

PMID- 17536000
TI  - Improvement in growth after two years of growth hormone therapy in very young
      children born small for gestational age and without spontaneous catch-up growth:
      results of a multicenter, controlled, randomized, open clinical trial.
AB  - CONTEXT: GH treatment is effective in children born small for gestational age
      (SGA); however, its effectiveness and safety in very young SGA children is
      unknown. OBJECTIVE: The aim was to analyze the outcome of very young SGA children
      treated with GH and followed for 2 yr. The results after 24 months of treatment,
      compared with a control group without treatment during 12 months followed by 12
      months of treatment, are shown. DESIGN: We performed a multicenter, controlled,
      randomized, open trial. SETTINGS: The pediatric endocrinology departments of 14
      public hospitals in Spain participated in the study. PATIENTS: Seventy-six
      children, aged 2-5 yr born SGA and without catch-up growth, were studied.
      INTERVENTION: Children received GH at 0.06 mg/kg.d for 2 yr (group I) or were
      followed for 12 months with no treatment and then treated for 12 months (group
      II). MAIN OUTCOME MEASURES: Age, general health status, pubertal stage, bone age,
      height, weight, biochemical and hormonal analyses, and adverse side effects were
      determined at biannual check-ups. RESULTS: The mean height sd score gain for
      chronological age in children treated for 24 months (group I) was 2.10, whereas
      in those treated only during the last 12 months (group II) was 1.43. In both
      groups, children under 4 yr of age had the greatest gain in growth velocity. No
      significant acceleration of bone age or side effects related to treatment was
      seen. CONCLUSION: Very young SGA children without spontaneous catch-up growth
      could benefit from GH treatment because growth was accelerated and no negative
      side effects were observed.

PMID- 17536002
TI  - Brain white matter expansion in human obesity and the recovering effect of
      dieting.
AB  - CONTEXT AND OBJECTIVE: Obesity is associated with several metabolic
      abnormalities. Recent studies suggest that obesity also affects brain function
      and is a risk factor for some degenerative brain diseases. The objective of this
      study was to examine the effects of weight gain and weight loss on brain gray and
      white matter structure. We hypothesized that possible differences seen in the
      brains of obese subjects would disappear or diminish after an intensive dieting
      period. METHODS: In part I of the study, we scanned with magnetic resonance
      imaging 16 lean (mean body mass index, 22 kg/m(2)) and 30 obese (mean body mass
      index, 33 kg/m(2)) healthy subjects. In part II, 16 obese subjects continued with
      a very low-calorie diet for 6 wk, after which they were scanned again. Regional
      brain white and gray matter volumes were calculated using voxel-based
      morphometry. RESULTS: White matter volumes were greater in obese subjects,
      compared with lean subjects in several basal brain regions, and obese individuals
      showed a positive correlation between white matter volume in basal brain
      structures and waist to hip ratio. The detected white matter expansion was
      partially reversed by dieting. Regional gray matter volumes did not differ
      significantly in obese and lean subjects, and dieting did not affect gray matter.
      CONCLUSIONS: The precise mechanism for the discovered white matter changes
      remains unclear, but the present study demonstrates that obesity and dieting are
      associated with opposite changes in brain structure. It is not excluded that
      white matter expansion in obesity has a role in the neuropathogenesis of
      degenerative brain diseases.

PMID- 17536001
TI  - Normocalcemic primary hyperparathyroidism: further characterization of a new
      clinical phenotype.
AB  - CONTEXT: Patients with elevated PTH and consistently normal serum calcium levels,
      in whom secondary causes of hyperparathyroidism have been excluded, may represent
      the earliest presentation of primary hyperparathyroidism (PHPT). OBJECTIVE: The
      objective of the study was to characterize patients with normocalcemic PHPT
      referred to a bone disease unit. DESIGN: This was a longitudinal cohort study.
      SETTING: Ambulatory patients were referred to the metabolic bone disease unit.
      PATIENTS: The study population included 37 patients [aged 58 yr, range 32-78; 95%
      female; serum calcium, 9.4 +/- 0.1 (sem) mg/dl (2.3 +/- 0.02 mmol/liter),
      reference range, 8.5-10.4 (2.1-2.6 mmol/liter); PTH, 93 +/- 5 pg/ml].
      INTERVENTIONS: Interventions included yearly (median 3 yr; range 1-8 yr) physical
      examination, biochemical indices, and bone mineral density (BMD). MAIN OUTCOME
      MEASURES: We measured the development of features of PHPT. RESULTS: Evaluation
      for classical features of PHPT revealed a history of kidney stones in five (14%),
      fragility fractures in four (11%), and osteoporosis in 57% [spine (34%), hip
      (38%), and/or distal one third radius (28%)]. BMD did not show preferential bone
      loss at the distal one third radius (T scores: spine, -2.00 +/- 0.25; hip, -1.84
      +/- 0.18; one third radius, -1.74 +/- 0.22). Further signs of PHPT developed in
      40% (seven hypercalcemia; one kidney stone; one fracture; two marked
      hypercalciuria; six had >10% BMD loss at one or more site(s) including four
      patients developing World Health Organization criteria for osteoporosis). Seven
      patients (three hypercalcemic, four persistently normocalcemic) underwent
      successful parathyroidectomy. CONCLUSIONS: Patients seen in a referral center
      with normocalcemic hyperparathyroidism have more substantial skeletal involvement
      than is typical in PHPT and develop more features and complications over time.
      These patients may represent the earliest form of symptomatic, rather than
      asymptomatic, PHPT.

PMID- 17536003
TI  - Pituitary-specific expression and Pit-1 regulation of the rat growth hormone
      releasing hormone receptor gene.
AB  - The GHRH receptor is expressed in the somatotroph cell of the anterior pituitary,
      where it functions to mediate GHRH-stimulated GH release. To study pituitary and
      somatotroph cell-specific expression of this gene, a transgenic mouse model and
      complementary cell culture experiments were developed. The activity of the 1.6-kb
      proximal rat GHRH receptor promoter was examined in vivo by generating transgenic
      mice with the promoter directing expression of a luciferase reporter. The
      promoter directs tissue-specific expression; luciferase is highly expressed in
      the pituitary but absent from 14 other tissues. Immunocytochemistry experiments
      show that transgene expression is targeted to GH-expressing somatotroph cells.
      The transgene is 5-fold more highly expressed in males than females, and there is
      an increase in transgene expression leading up to the onset of puberty. The 1.6
      kb promoter was further examined in cell culture experiments, which revealed that
      the promoter is selectively activated in pituitary cells and that promoter
      reporter expression in nonpituitary cells can be enhanced by the pituitary
      specific transcription factor Pit-1. EMSAs identified 10 short regions that
      specifically bind Pit-1 with highly variable relative affinities. The highest
      affinity site was previously identified and is required for Pit-1 activation of
      the promoter. Four additional sites contribute to Pit-1 regulation of the
      promoter and are important to achieving full activation of the gene. The results
      show that the 1.6-kb promoter is sufficient to direct tissue- and cell-specific
      expression in vivo and is regulated by Pit-1.

PMID- 17536004
TI  - Steroid receptor phosphorylation: a key modulator of multiple receptor functions.
AB  - Steroid receptors are hormone-activated transcription factors, the expression and
      activities of which are also highly dependent upon posttranslational
      modifications including phosphorylation. The remarkable number of phosphorylation
      sites in these receptors and the wide variety of kinases participating in their
      phosphorylation facilitate integration between cell-signaling pathways and
      steroid receptor action. Sites have been identified in all of the functional
      domains although the sites are predominantly in the amino-terminal portions of
      the receptors. Regulation of function is receptor specific, site specific, and
      often dependent upon activation of a specific cell-signaling pathway. This
      complexity explains, in part, the early difficulties in identifying roles for
      phosphorylation in receptor function. With increased availability of
      phosphorylation site-specific antibodies and better means to measure receptor
      activities, numerous roles for site-specific phosphorylation have been identified
      including sensitivity of response to hormone, DNA binding, expression, stability,
      subcellular localization, and protein-protein interactions that determine the
      level of regulation of specific target genes. This review summarizes current
      knowledge regarding receptor phosphorylation and regulation of function. As
      functional assays become more sophisticated, it is likely that additional roles
      for phosphorylation in receptor function will be identified.

PMID- 17536005
TI  - Mechanisms regulating oocyte meiotic resumption: roles of mitogen-activated
      protein kinase.
AB  - Oocyte meiotic maturation is one of the important physiological requirements for
      species survival. However, little is known about the detailed events occurring
      during this process. A number of studies have demonstrated that MAPK plays a
      pivotal role in the regulation of meiotic cell cycle progression in oocytes, but
      controversial findings have been reported in both lower vertebrates and mammals.
      In this review, we summarized the roles of MAPK cascade and related signal
      pathways in oocyte meiotic reinitiation in both lower vertebrates and mammals. We
      also tried to reconcile the paradoxical results and highlight the new findings
      concerning the function of MAPK in both oocytes and the surrounding follicular
      somatic cells. The unresolved questions and future research directions regarding
      the role of MAPK in meiotic resumption are addressed.

PMID- 17536006
TI  - Nuclear receptor coregulator (NRC): mapping of the dimerization domain,
      activation of p53 and STAT-2, and identification of the activation domain AD2
      necessary for nuclear receptor signaling.
AB  - Nuclear receptor coregulator (NRC) is a 250-kDa nuclear protein involved in
      transcriptional activation of nuclear hormone receptors, nuclear factor-kappaB, c
      Jun, c-Fos, and cAMP response element-binding protein. NRC is organized into a
      modular structure consisting of two activation domains (AD1 and AD2), two nuclear
      hormone receptor-interacting motifs, LxxLL-1 and LxxLL-2, and a C-terminal
      regulatory region rich in serines, threonines, and leucines. The LxxLL-1 motif of
      NRC binds to a broad spectrum of nuclear hormone receptors with high affinity
      whereas LxxLL-2 interacts with a very limited number of receptors. In this study
      we present further evidence that NRC can act as a dimer and have identified a
      dimerization region of 146 amino acids including LxxLL-1. Mutation of the core
      LxxLL-1 motif, however, indicates that it is not involved in the dimerization of
      NRC. AD2, just C-terminal of LxxLL-1, was found to play a central role in ligand
      dependent activation by nuclear receptors even though AD1 exhibits more potent
      intrinsic activity. Thus, a short region of approximately 300 amino acids
      including and flanking LxxLL-1 plays an important role in NRC dimerization and
      nuclear receptor binding and transcriptional activation. In addition, consistent
      with its role as a cointegrator for transcriptional activation, NRC also
      functions as a coactivator for signal transducer and activator of transcription 2
      (STAT-2) and p53. Activation of p53 by NRC appears to involve a novel mechanism
      where NRC interacts indirectly with p53 through Trap80, a member of the mediator
      complex, which binds NRC interacting factor-1 (NIF-1), which interacts with and
      potentiates the effect of NRC.

PMID- 17536007
TI  - Follicle-stimulating hormone induces multiple signaling cascades: evidence that
      activation of Rous sarcoma oncogene, RAS, and the epidermal growth factor
      receptor are critical for granulosa cell differentiation.
AB  - FSH regulates ovarian granulosa cell differentiation not only by activating
      adenylyl cyclase and protein kinase A (PKA) but also by other complex mechanisms.
      Using primary rat granulosa cell cultures, we provide novel evidence that FSH
      rapidly activates two small GTP-binding proteins RAP1 and RAS. FSH activation of
      RAP1 requires cAMP-mediated activation of exchange factor activated by
      cAMP/RAPGEF3 whereas FSH activation of RAS and downstream signaling cascades
      involves multiple factors. Specifically, FSH activation of RAS required Rous
      sarcoma oncogene (SRC) family tyrosine kinase (SFK) and epidermal growth factor
      receptor (EGFR) tyrosine kinase activities but not PKA. FSH-induced
      phosphorylation of ERK1/2 was blocked by dominant-negative RAS as well as by
      inhibitors of EGFR tyrosine kinase, metalloproteinases involved in growth factor
      shedding, and SFKs. In contrast, FSH-induced phosphorylation of protein kinase B
      (PKB/AKT) and the Forkhead transcription factor, FOXO1a occurred by SFK-dependent
      but RAS-independent mechanisms. The SFKs, c-SRC and FYN, and the SRC-related
      tyrosine kinase ABL were present and phosphorylated rapidly in response to FSH.
      Lastly, the EGF-like factor amphiregulin (AREG) activated RAS and ERK1/2
      phosphorylation in granulosa cells by mechanisms that were selectively blocked by
      an EGFR antagonist but not by an SFK antagonist. However, AREG-mediated
      phosphorylation of PKB and FOXO1a required both EGFR and SFK activation.
      Moreover, we show that FSH induces AREG and that activation of the EGFR impacts
      granulosa cell differentiation and the expression of genes characteristic of the
      luteal cell phenotype. Thus, FSH orchestrates the coordinate activation of three
      diverse membrane-associated signaling cascades (adenylyl cyclase, RAS, and SFKs)
      that converge downstream to activate specific kinases (PKA, ERK1/2, and
      PKB/FOXO1a) that control granulosa cell function and differentiation.

PMID- 17536008
TI  - Roles of protein kinase C and actin-binding protein 280 in the regulation of
      intracellular trafficking of dopamine D3 receptor.
AB  - D(3) dopamine receptor (D(3)R) is expressed mainly in parts of the brain that
      control the emotional behaviors. It is believed that the improper regulation of
      D(3)R is involved in the etiology of schizophrenia. Desensitization of D(3)R is
      weakly associated with G protein-coupled receptor kinase (GRK)/beta-arrestin
      directed internalization. This suggests that there might be an alternative
      pathway that regulates D(3)R signaling. This report shows that D(3)R undergoes
      robust protein kinase C (PKC)-dependent sequestration that is accompanied by
      receptor phosphorylation and the desensitization of signaling. PKC-dependent
      D(3)R sequestration, which was enhanced by PKC-beta or -delta, was dynamin
      dependent but independent of GRK, beta-arrestin, or caveolin 1. Site-directed
      mutagenesis of all possible phosphorylation sites within the intracellular loops
      of D(3)R identified serine residues at positions 229 and 257 as the critical
      amino acids responsible for phorbol-12-myristate-13-acetate (PMA)-induced D(3)R
      phosphorylation, sequestration, and desensitization. In addition, the LxxY
      endocytosis motif, which is located between residues 252 and 255, was found to
      play accommodating roles for PMA-induced D(3)R sequestration. A continuous
      interaction with the actin-binding protein 280 (filamin A), which was previously
      known to interact with D(3)R, is required for PMA-induced D(3)R sequestration. In
      conclusion, the PKC-dependent but GRK-/beta-arrestin-independent phosphorylation
      of D(3)R is the main pathway responsible for the sequestration and
      desensitization of D(3)R. Filamin A is essential for both the efficient signaling
      and sequestration of D(3)R.

PMID- 17536009
TI  - Estrogen deprivation and inhibition of breast cancer growth in vivo through
      activation of the orphan nuclear receptor liver X receptor.
AB  - Estrogen plays an important role in normal physiology. It is also a risk factor
      for breast cancer, and antiestrogen therapies have been shown to be effective in
      the treatment and prevention of breast cancers. The liver is important for
      estrogen metabolism, and a compromised liver function has been linked to
      hyperestrogenism in patients. In this report, we showed that the liver X receptor
      (LXR) controls estrogen homeostasis by regulating the basal and inducible hepatic
      expression of estrogen sulfotransferase (Est, or Sult1e1), an enzyme critical for
      metabolic estrogen deactivation. Genetic or pharmacological activation of LXR
      resulted in Est induction, which in turn inhibited estrogen-dependent uterine
      epithelial cell proliferation and gene expression, as well as breast cancer
      growth in a nude mouse model of tumorigenicity. We further established that Est
      is a transcriptional target of LXR, and deletion of the Est gene in mice
      abolished the LXR effect on estrogen deprivation. Interestingly, Est regulation
      by LXR appeared to be liver specific, further underscoring the role of liver in
      estrogen metabolism. Activation of LXR failed to induce other major estrogen
      metabolizing enzymes, suggesting that the LXR effect on estrogen metabolism is
      Est specific. In summary, our results have revealed a novel mechanism controlling
      estrogen homeostasis in vivo and may have implications for drug development in
      the treatment of breast cancer and other estrogen-related cancerous endocrine
      disorders.

PMID- 17536010
TI  - Heterooligomerization between vasotocin and corticotropin-releasing hormone (CRH)
      receptors augments CRH-stimulated 3',5'-cyclic adenosine monophosphate
      production.
AB  - In birds, ACTH release from the anterior pituitary gland during stress is
      controlled by CRH and arginine vasotocin (AVT). Using 5-wk-old male chicks,
      simultaneous iv injections of CRH and AVT were found to result in a greater than
      additive increase in plasma corticosterone levels compared with that obtained
      with individual administration of either peptide hormone. In order to investigate
      molecular mechanisms underlying this observation, the chicken CRH receptor (CRHR)
      and vasotocin VT2 receptor (VT2R) were fused to cyan and yellow fluorescent
      proteins and expressed in HeLa cells. The resulting CRHR and VT2R fusion proteins
      were expressed appropriately in the plasma membrane and were found to couple to
      downstream signal transduction pathways. Quantitative fluorescence resonance
      energy transfer (FRET) analysis was used to determine whether the CRHR and VT2R
      formed heterodimers. In the absence of CRH and AVT, the FRET efficiency was 15
      18%, and the distance between receptors was 5-6 nm. Treatment of the cells that
      expressed both cyan fluorescent protein-CRHR and yellow fluorescent protein-VT2R
      with CRH or AVT alone did not lead to a significant change in the FRET
      efficiency. However, simultaneous addition of these hormones increased the
      efficiency of the FRET signal and decreased the distance between the two
      receptors. In HeLa cells expressing both CRHR and VT2R, treatment with CRH and
      AVT resulted in a significant increase in cAMP production over that with CRH
      alone, indicating that heterodimer formation may enhance the ability of the CRHR
      to activate downstream signal transduction.

PMID- 17536011
TI  - Targeted cancer therapy with a novel low-dose rate alpha-emitting
      radioimmunoconjugate.
AB  - Alpha-emitting radionuclides are highly cytotoxic and are of considerable
      interest in the treatment of cancer. A particularly interesting approach is in
      radioimmunotherapy. However, alpha-emitting antibody conjugates have been
      difficult to exploit clinically due to the short half-life of the radionuclides,
      low production capability, or limited source materials. We have developed a novel
      technology based on the low-dose rate alpha-particle-emitting nuclide (227)Th,
      exemplified here using the monoclonal antibody rituximab. In vitro, this
      radioimmunoconjugate killed lymphoma cells at Becquerel per milliliter (Bq/mL)
      levels. A single injection of (227)Th-rituximab induced complete tumor regression
      in up to 60% of nude mice bearing macroscopic (32-256 mm(3)) human B-lymphoma
      xenografts at Becquerel per gram (Bq/g) levels without apparent toxicity. Therapy
      with (227)Th-rituximab was significantly more effective than the control
      radioimmunoconjugate (227)Th-trastuzumab and the standard beta-emitting
      radioimmunoconjugate for CD20(+) lymphoma(90)Y-tiuxetan-ibritumomab. Thorium-227
      based constructs may provide a novel approach for targeted therapy against a wide
      variety of cancers.

PMID- 17536012
TI  - The Hedgehog receptor Patched controls lymphoid lineage commitment.
AB  - A first step in hematopoiesis is the specification of the lymphoid and myeloid
      lineages from multipotent progenitor cells in the bone marrow. Using a
      conditional ablation strategy in adult mice, we show that this differentiation
      step requires Patched (Ptch), the cell surface-bound receptor for Hedgehog (Hh).
      In the absence of Ptch, the development of T- and B-lymphoid lineages is blocked
      at the level of the common lymphoid progenitor in the bone marrow. Consequently,
      the generation of peripheral T and B cells is abrogated. Cells of the myeloid
      lineage develop normally in Ptch mutant mice. Finally, adoptive transfer
      experiments identified the stromal cell compartment as a critical Ptch-dependent
      inducer of lymphoid versus myeloid lineage commitment. Our data show that Ptch
      acts as a master switch for proper diversification of hematopoietic stem cells in
      the adult organism.

PMID- 17536013
TI  - The syndecan-1 heparan sulfate proteoglycan is a viable target for myeloma
      therapy.
AB  - The heparan sulfate proteoglycan syndecan-1 is expressed by myeloma cells and
      shed into the myeloma microenvironment. High levels of shed syndecan-1 in myeloma
      patient sera correlate with poor prognosis and studies in animal models indicate
      that shed syndecan-1 is a potent stimulator of myeloma tumor growth and
      metastasis. Overexpression of extracellular endosulfatases, enzymes which remove
      6-O sulfate groups from heparan sulfate chains, diminishes myeloma tumor growth
      in vivo. Together, these findings identify syndecan-1 as a potential target for
      myeloma therapy. Here, 3 different strategies were tested in animal models of
      myeloma with the following results: (1) treatment with bacterial heparinase III,
      an enzyme that degrades heparan sulfate chains, dramatically inhibited the growth
      of primary tumors in the human severe combined immunodeficient (SCID-hu) model of
      myeloma; (2) treatment with an inhibitor of human heparanase, an enzyme that
      synergizes with syndecan-1 in promoting myeloma progression, blocked the growth
      of myeloma in vivo; and (3) knockdown of syndecan-1 expression by RNAi diminished
      and delayed myeloma tumor development in vivo. These results confirm the
      importance of syndecan-1 in myeloma pathobiology and provide strong evidence that
      disruption of the normal function or amount of syndecan-1 or its heparan sulfate
      chains is a valid therapeutic approach for this cancer.

PMID- 17536014
TI  - Endothelial progenitor cell derived microvesicles activate an angiogenic program
      in endothelial cells by a horizontal transfer of mRNA.
AB  - Membrane-derived microvesicles (MVs) are released from the cell surface and are
      implicated in cell-to-cell communication. We evaluated whether MVs derived from
      endothelial progenitor cells (EPCs) are able to trigger angiogenesis. We found
      that EPC-derived MVs were incorporated in endothelial cells by interaction with
      alpha4 and beta1 integrins expressed on the MV surface. In vitro, MVs promoted
      endothelial cell survival, proliferation, and organization in capillary-like
      structures. In vivo, in severe combined immunodeficient (SCID) mice, MV
      stimulated human endothelial cells organized in patent vessels. When incubated
      with RNase, despite their internalization into endothelial cells, MVs failed to
      induce in vitro and in vivo angiogenic effects. mRNA transfer was shown by
      transduction of GFP protein in endothelial cells by MVs containing GFP-mRNA and
      the biologic relevance by the angiogenic effect of MV-mRNA extract delivered by
      lipofectamine. Microarray ana-lysis and quantitative reverse transcription
      polymerase chain reaction (RT-PCR) of MV-mRNA extract indicated that MVs were
      shuttling a specific subset of cellular mRNA, such as mRNA associated with the
      PI3K/AKT signaling pathway. Protein expression and functional studies showed that
      PI3K and eNOS play a critical role in the angiogenic effect of MVs. These results
      suggest that EPCs may activate angiogenesis in endothelial cells by releasing MVs
      able to trigger an angiogenic program.

PMID- 17536015
TI  - Activity of vincristine, L-ASP, and dexamethasone against acute lymphoblastic
      leukemia is enhanced by the BH3-mimetic ABT-737 in vitro and in vivo.
AB  - Defects in apoptosis signaling contribute to poor outcome in pediatric acute
      lymphoblastic leukemia (ALL), and overexpression of antiapoptotic Bcl-2 (Bcl-2
      and Bcl-X(L)) family proteins has been observed in ALL. ABT-737 is a small
      molecule BH3-mimetic that inhibits the antiapoptotic Bcl-2 family proteins. We
      evaluated the cytotoxicity of ABT-737 in combination with vincristine,
      dexamethasone, and L-asparaginase (VXL) in 7 ALL cell lines. Multilog synergistic
      cytotoxicity was observed in all 7 cell lines with ABT-737 plus L-asparaginase or
      vincristine, and in 5 of 7 cell lines with ABT-737 plus dexamethasone or VXL. In
      leukemia cells, but not in normal lymphocytes, ABT-737 plus L-asparaginase
      induced greater mitochondrial depolarization (JC-1 staining); mitochondrial
      cytochrome c release; activation of Bax, Bid, and caspases (immunoblotting); and
      eventually apoptosis (annexin V staining) than did either drug alone. In mouse
      xenografts derived from patients with ALL at diagnosis (ALL-7) or at relapse (ALL
      19), event-free survival (EFS) was significantly enhanced with ABT-737 plus VXL
      relative to VXL or ABT-737 alone (P </= .02). Thus, ABT-737 synergistically
      enhanced VXL cytotoxicity in ALL cell lines via a mitochondrial death pathway and
      enhanced EFS in VXL-treated mice bearing ALL xenografts. Combining VXL with a BH3
      mimetic warrants clinical investigation in ALL at relapse and potentially in
      chemotherapy-resistant ALL subgroups.

PMID- 17536016
TI  - Activation of mitogen-activated protein kinase kinase (MEK)/extracellular signal
      regulated kinase (ERK) signaling pathway is involved in myeloid lineage
      commitment.
AB  - Common lymphoid progenitors (CLPs) are lymphoid-lineage-committed progenitor
      cells. However, they maintain a latent myeloid differentiation potential that can
      be initiated by stimulation with interleukin-2 (IL-2) via ectopically expressed
      IL-2 receptors. Although CLPs express IL-7 receptors, which share the common
      gamma chain with IL-2 receptors, IL-7 cannot initiate lineage conversion in CLPs.
      In this study, we demonstrate that the critical signals for initiating lineage
      conversion in CLPs are delivered via IL-2 receptor beta (IL-2R beta)
      intracellular domains. Fusion of the A region of the IL-2R beta cytoplasmic tail
      to IL-7R alpha enables IL-7 to initiate myeloid differentiation in CLPs. We found
      that Shc, which associates with the A region, mediates lineage conversion signals
      through the mitogen activated protein kinase (MAPK) pathway. Because mitogen
      activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK)
      inhibitors completely blocked IL-2-mediated lineage conversion, MAPK activation,
      specifically via the MEK/ERK pathway, is critically involved in the initiation of
      this event. Furthermore, formation of granulocyte/macrophage (GM) colonies by
      hematopoietic stem cells, but not by common myeloid progenitors (CMPs), was
      severely reduced in the presence of MEK/ERK inhibitors. These results demonstrate
      that activation of MEK/ERK plays an important role in GM lineage commitment.

PMID- 17536017
TI  - Tissue factor: a link between C5a and neutrophil activation in antiphospholipid
      antibody induced fetal injury.
AB  - Fetal loss in patients with antiphospholipid (aPL) antibodies has been ascribed
      to thrombosis of placental vessels. However, we have shown that inflammation,
      specifically activation of complement with generation of the anaphylotoxin C5a,
      is an essential trigger of fetal injury. In this study, we analyzed the role of
      the procoagulant molecule tissue factor (TF) in a mouse model of aPL antibody
      induced pregnancy loss. We found that either blockade of TF with a monoclonal
      antibody in wild-type mice or a genetic reduction of TF prevented aPL antibody
      induced inflammation and pregnancy loss. In response to aPL antibody-generated
      C5a, neutrophils express TF potentiating inflammation in the deciduas and leading
      to miscarriages. Importantly, we showed that TF in myeloid cells but not fetal
      derived cells (trophoblasts) was associated with fetal injury, suggesting that
      the site for pathologic TF expression is neutrophils. We found that TF expression
      in neutrophils contributes to respiratory burst and subsequent trophoblast injury
      and pregnancy loss induced by aPL antibodies. The identification of TF as an
      important mediator of C5a-induced oxidative burst in neutrophils in aPL-induced
      fetal injury provides a new target for therapy to prevent pregnancy loss in the
      antiphospholipid syndrome.

PMID- 17536018
TI  - Farnesyl transferase inhibitor resistance probed by target mutagenesis.
AB  - Mutation in the target oncoprotein is a common mechanism of resistance to
      tyrosine kinase inhibitors, as exemplified by the many BCR/ABL mutations that
      thwart imatinib activity in patients with chronic myelogenous leukemia. It
      remains unclear whether normal cellular protein targets of chemotherapeutics will
      evolve drug resistance via mutation to a similar extent. We conducted an in vitro
      screen for resistance to lonafarnib, a farnesyl protein transferase inhibitor
      that blocks prenylation of a number of proteins important in cell proliferation,
      and identified 9 mutations clustering around the lonafarnib binding site. In
      patients treated with a combination of imatinib and lonafarnib, we identified
      farnesyl protein transferase mutations in residues identified in our screen.
      Substitutions at Y361 were found in patients prior to treatment initiation,
      suggesting that these mutants might confer a proliferative advantage to leukemia
      cells, which we were able to confirm in cell culture. In vitro mutagenesis of
      normal cellular enzymes can be exploited to identify mutations that confer
      chemotherapy resistance to novel agents.

PMID- 17536020
TI  - Identification of positional candidate genes for body weight and adiposity in
      subcongenic mice.
AB  - We previously constructed a congenic mouse, B6.S-D2Mit194-D2Mit311 (B6.S-2) with
      27 Mb of SPRET/Ei donor DNA on distal chromosome 2 in a C57BL/6J background that
      captured an obesity quantitative trait locus (QTL). Mice homozygous for SPRET/Ei
      alleles at the donor region had decreased body weight and obesity-related
      phenotypes (Diament AL, Farahani P, Chiu S, Fisler J, Warden CH. Mamm Genome 15:
      452-459, 2004). In this study, we constructed five overlapping subcongenics with
      smaller SPRET/Ei donor regions to fine map the underlying gene(s). One of the
      five subcongenic lines derived from the B6.S-2 founding congenic, B6.S-2A,
      captured the body weight and adiposity phenotypes in a donor region with a
      maximum size of 7.4 Mb. Homozygous SPRET/Ei donor alleles in both the founding
      congenic and the derived B6.S-2A subcongenic exhibited significant decreases in
      body weight, multiple fat pad weights, and adiposity index (total fat pad weight
      divided by body weight). Interval-specific microarray analysis in four tissues
      for donor region genes from the founding B6.S-2 congenic identified several
      differentially expressed genes mapping to the B6.S-2A subcongenic donor region,
      including prohormone convertase 2 (PC2; gene name: Pcsk2). Quantitative real-time
      PCR confirmed a modest decrease of PC2 expression in brains of mice homozygous
      for SPRET/Ei donor alleles. Analysis of the relative levels of mRNA for B6 and
      SPRET/Ei in heterozygous congenic mice showed differentially higher expression of
      the C57BL/6J allele over the SPRET/Ei allele, indicating a cis regulation of
      differential expression. Using subcongenic mapping, we successfully narrowed a
      body weight and obesity QTL interval and identified PC2 as a positional candidate
      gene.

PMID- 17536019
TI  - Platelet activation in patients with sickle disease, hemolysis-associated
      pulmonary hypertension, and nitric oxide scavenging by cell-free hemoglobin.
AB  - Increased platelet activation is recognized in patients with sickle cell disease
      (SCD), but its pathogenesis and clinical relevance remain uncertain. Pulmonary
      arterial hypertension (PAH), an important complication of SCD, is characterized
      by a proliferative pulmonary vasculopathy, in situ thrombosis, and vascular
      dysfunction related to scavenging of nitric oxide (NO) by hemoglobin released
      into blood plasma during intravascular hemolysis. We investigated links between
      platelet activation, PAH and NO scavenging in patients with SCD. Platelet
      activation marked by activated fibrinogen receptor correlated to the severity of
      PAH (r = 0.58, P < .001) and to laboratory markers of intravascular hemolysis,
      such as reticulocyte count (r = 0.44, P = .02). In vitro exposure of platelets to
      pathologically relevant concentrations of cell-free hemoglobin promoted basal-
      and agonist-stimulated activation and blocked the inhibitory effects on platelet
      activation by an NO donor. In patients with SCD, administration of sildenafil, a
      phosphodiesterase-5 inhibitor that potentiates NO-dependent signaling, reduced
      platelet activation (P = .01). These findings suggest a possible interaction
      between hemolysis, decreased NO bioavailability, and pathologic platelet
      activation that might contribute to thrombosis and pulmonary hypertension in SCD,
      and potentially other disorders of intravascular hemolysis. This supports a role
      for NO-based therapeutics for SCD vasculopathy. This trial was registered at
      www.clinicaltrials.gov as no. NCT00352430.

PMID- 17536021
TI  - Fasting-induced changes in ECL cell gene expression.
AB  - Gastric enterochromaffin-like (ECL) cells release histamine in response to food
      because of elevation of gastrin and neural release of pituitary adenylate cyclase
      activating peptide (PACAP). Acid secretion is at a basal level in the absence of
      food but is rapidly stimulated with feeding. Rats fasted for 24 h showed a
      significant decrease of mucosal histamine despite steady-state expression of the
      histamine-synthesizing enzyme histidine decarboxylase (HDC). Comparative
      transcriptomal analysis using gene expression oligonucleotide microarrays of 95%
      pure ECL cells from fed and 24-h fasted rats, thereby eliminating mRNA
      contamination from other gastric mucosal cell types, identified significantly
      increased gene expression of the enzymes histidase and urocanase catabolizing the
      HDC substrate L-histidine but significantly decreased expression of the cellular
      L-histidine uptake transporter SN2 and of the vesicular monoamine transporter 2
      (VMAT-2) responsible for histamine uptake into secretory vesicles. This was
      confirmed by reverse transcriptase-quantitative polymerase chain reaction of
      gastric fundic mucosal samples from fed and 24-h fasted rats. The decrease of
      VMAT-2 gene expression was also shown by a decrease in VMAT-2 protein content in
      protein extracts from fed and 24-h fasted rats compared with equal amounts of HDC
      protein and Na-K-ATPase alpha(1)-subunit protein content. These results indicate
      that rat gastric ECL cells regulate their histamine content during 24-h fasting
      not by a change in HDC gene or protein expression but by regulation of substrate
      concentration for HDC and a decreased histamine secretory pool.

PMID- 17536022
TI  - Role of STAT5a in regulation of sex-specific gene expression in female but not
      male mouse liver revealed by microarray analysis.
AB  - Sexual dimorphism in mammalian liver impacts genes affecting hepatic physiology,
      including inflammatory responses, diseased states, and the metabolism of steroids
      and foreign compounds. Liver sex specificity is dictated by sex differences in
      pituitary growth hormone (GH) secretion, with the transcription factor signal
      transducer and activator of transcription (STAT)5b required for intracellular
      signaling initiated by the pulsatile male plasma GH profile. STAT5a, a minor
      liver STAT5 form >90% identical to STAT5b, also responds to sexually dimorphic
      plasma GH stimulation but is unable to compensate for the loss of STAT5b and the
      associated loss of sex-specific liver gene expression. A large-scale gene
      expression study was conducted using 23,574-feature oligonucleotide microarrays
      and livers of male and female mice, both wild-type and Stat5a-inactivated mice,
      to elucidate any dependence of liver gene expression on STAT5a. Significant sex
      differences in expression were found for 2,482 mouse genes, 1,045 showing higher
      expression in males and 1,437 showing higher expression in females. In contrast
      to the widespread effects of the loss of STAT5b, STAT5a deficiency had a limited
      but well-defined impact on liver sex specificity, with 219 of 1,437 female
      predominant genes (15%) specifically decreased in expression in STAT5a-deficient
      female liver. Analysis of liver RNAs from wild-type mice representing three mixed
      or outbred strains identified 1,028 sexually dimorphic genes across the strains,
      including 393 female-predominant genes, of which 89 (23%) required STAT5a for
      normal expression in female liver. These findings highlight the importance of
      STAT5a for regulation of sex-specific gene expression specifically in female
      liver, in striking contrast to STAT5b, whose major effects are restricted to male
      liver.

PMID- 17536023
TI  - Quantitative analysis of liver metabolites in three stages of the circannual
      hibernation cycle in 13-lined ground squirrels by NMR.
AB  - Thirteen-lined ground squirrels and other circannual hibernators undergo profound
      physiological changes on an annual basis, transitioning from summer homeothermy
      [body temperature (T(b)) approximately 37 degrees C] to winter heterothermy (T(b)
      cycling between 0 degrees C and 37 degrees C). We hypothesize that these
      physiological changes are reflected in biochemical changes that provide
      mechanistic insights into, and biomarkers for, hibernation states. Here we report
      the results of an NMR-based metabolomics analysis of liver extracts from ground
      squirrels in three distinct physiological states of circannual hibernation:
      summer active (SA), late torpor (LT), and reentering torpor (Ent) after one of
      the euthermic arousals. Of the 43 identified and quantified metabolites, 36
      differed among these three states and fell into two patterns of variation: 1) SA
      differed from both of the two winter states; or 2) the two winter states differed
      from each other, but one of the two was not different from SA. Concentrations of
      hepatic glucose, lactate, alanine, succinate, beta-hydroxybutyrate, glutamine,
      and betaine were identified as robust hepatic biomarkers that together
      distinguish among animals in these three states of the circannual hibernation
      rhythm. These data are consistent with a proposed two-switch model of
      hibernation, in which setting the summer-winter switch to winter enables
      expression of a distinct torpor-arousal switch. The summer-winter switch is
      characterized by the metabolites associated with the well-known switch from
      carbohydrate to lipid fuel utilization during hibernation. The torpor-arousal
      switch is characterized by the accumulation of metabolites of nitrogen
      (glutamine) and phospholipid (betaine) catabolism in LT with the capacity to act
      as protective osmolytes.

PMID- 17536024
TI  - The laws of attraction: chemokines, neutrophils and eosinophils in severe
      exacerbations of asthma.

PMID- 17536025
TI  - Dietary supplements and asthma: another one bites the dust.

PMID- 17536026
TI  - Gastro-oesophageal reflux and tachykinins in asthma and chronic cough.

PMID- 17536027
TI  - Systemic inflammation and progression of COPD.

PMID- 17536028
TI  - Unsuspected pulmonary embolism on CT scanning: yet another headache for
      clinicians?

PMID- 17536029
TI  - Acute renal failure in people with cystic fibrosis.

PMID- 17536031
TI  - Respiratory disease in the ophthalmology department. Diagnosis: retinal
      vasculitis associated with tuberculoprotein hypersensitivity (Eales' disease).

PMID- 17536033
TI  - Challenges in pulmonary fibrosis. 1: Use of high resolution CT scanning of the
      lung for the evaluation of patients with idiopathic interstitial pneumonias.
AB  - High resolution CT (HRCT) scanning has contributed significantly to the
      evaluation of patients with interstitial lung disease and is particularly useful
      in the diagnosis of idiopathic pulmonary fibrosis (IPF). The characteristic
      radiographic features of the idiopathic interstitial pneumonias on HRCT scans
      have been increasingly analysed and are now fairly well described. Based on
      current data, HRCT scanning can provide a confident, highly specific diagnosis of
      IPF in many patients with diffuse lung disease. This article reviews an organised
      approach to HRCT scanning and identifies the features that allow an accurate
      diagnosis of the idiopathic interstitial pneumonias to be made. The role of
      surgical lung biopsy is discussed in the diagnosis of cases when a definite HRCT
      diagnosis cannot be made.

PMID- 17536034
TI  - Safety and tolerability of three consecutive bronchoscopies after allergen
      challenge in volunteers with mild asthma.

PMID- 17536035
TI  - Lung cancer in HIV infected patients.

PMID- 17536036
TI  - Macrophage enrichment from induced sputum.

PMID- 17536037
TI  - Lymphangioleiomyomatosis--presence of receptor tyrosine kinases and the
      angiogenesis factor VEGF-A as potential therapeutic targets.

PMID- 17536038
TI  - 18F-FDG PET scan as follow-up tool for sarcoidosis with symptomatic cardiac
      conduction disturbances requiring a pacemaker.

PMID- 17536039
TI  - Soluble RAGE blocks scavenger receptor CD36-mediated uptake of hypochlorite
      modified low-density lipoprotein.
AB  - Engagement of the receptor for advanced glycation end products (RAGE) by its
      signal transduction ligands evokes inflammatory cell infiltration and activation
      of the vessel wall. However, soluble RAGE (sRAGE), the truncated form spanning
      the extracellular binding domain of RAGE, has potent anti-inflammatory properties
      by acting as a decoy for RAGE ligands. We now show that sRAGE binds with high
      affinity to atherogenic low-density lipoprotein (LDL) modified by hypochlorous
      acid (HOCl), the major oxidant generated by the myeloperoxidase-H2O2-chloride
      system of phagocytes activated during inflammation. We further demonstrate that
      sRAGE can be coprecipitated with HOCl-LDL from spiked serum. To determine the
      functional significance of sRAGE binding to HOCl-LDL, cell association studies
      with macrophages were performed. sRAGE effectively inhibited cellular uptake of
      HOCl-LDL and subsequent lipid accumulation. Using Chinese hamster ovary cells
      overexpressing class B scavenger receptor CD36 or SR-BI, two preferential
      scavenger receptors for HOCl-LDL, we demonstrate that sRAGE only interferes with
      CD36-mediated uptake of HOCl-LDL. The present findings indicate that sRAGE acts
      as a sink for HOCl-LDL, which is abundantly present in human atherosclerotic
      lesions. We propose that sRAGE represents a physiological antagonist that
      interferes with scavenger receptor-mediated cholesterol accumulation and foam
      cell formation of macrophages.

PMID- 17536040
TI  - Imaging lung aeration and lung liquid clearance at birth.
AB  - Aeration of the lung and the transition to air-breathing at birth is fundamental
      to mammalian life and initiates major changes in cardiopulmonary physiology.
      However, the dynamics of this process and the factors involved are largely
      unknown, because it has not been possible to observe or measure lung aeration on
      a breath-by-breath basis. We have used the high contrast and spatial resolution
      of phase contrast X-ray imaging to study lung aeration at birth in spontaneously
      breathing neonatal rabbits. As the liquid-filled fetal lungs provide little
      absorption or phase contrast, they are not visible and only become visible as
      they aerate, allowing a detailed examination of this process. Pups were imaged
      live from birth to determine the timing and spatial pattern of lung aeration, and
      relative levels of lung aeration were measured from the images using a power
      spectral analysis. We report the first detailed observations and measurements of
      lung aeration, demonstrating its dependence on inspiratory activity and body
      position; dependent regions aerated at much slower rates. The air/liquid
      interface moved toward the distal airways only during inspiration, with little
      proximal movement during expiration, indicating that trans-pulmonary pressures
      play an important role in airway liquid clearance at birth. Using these imaging
      techniques, the dynamics of lung aeration and the critical role it plays in
      regulating the physiological changes at birth can be fully explored.

PMID- 17536041
TI  - Genetic polymorphisms in the human selenoprotein P gene determine the response of
      selenoprotein markers to selenium supplementation in a gender-specific manner
      (the SELGEN study).
AB  - Selenium (Se), a micronutrient essential for human health, is incorporated into
      at least 25 selenoproteins including selenoprotein P (SePP), which transports Se
      within the body. This research identified two single nucleotide polymorphisms
      (SNPs) in the SePP gene, one in the coding region (position 24731, causing an Ala
      to Thr change) and one in the 3'untranslated region (position 25191). Their
      frequency was similar in Caucasian, Chinese, and South Asian populations.
      Prospectively genotyped volunteers were supplemented for 6 wk with 100 microg
      sodium selenite/day. Blood samples were analyzed for plasma Se and selenoprotein
      biomarkers at baseline, after supplementation, and during a washout period.
      Plasma Se, SePP, and glutathione peroxidase 3 (GPx3) levels increased with
      supplementation. Baseline plasma Se content depended on both SePP genotypes and
      body mass index. Presupplementation SePP concentration was associated with gender
      and genotype at SNP 24731 and postsupplementation concentration with SNP 25191.
      Both SNPs and gender were associated with differences in GPx3 activity, plasma,
      and erythrocyte thioredoxin reductase 1 concentrations and lymphocyte glutathione
      peroxidase 1 and 4 activities and concentrations. In conclusion, the data reveal
      two common functional SNPs within the human SePP gene that may predict behavior
      of biomarkers of Se status and response to supplementation and thus
      susceptibility to disease.

PMID- 17536042
TI  - What message does the nuclear envelope hold?

PMID- 17536043
TI  - Visual rehabilitation: now you see it; now you don't.

PMID- 17536044
TI  - Multitissular involvement in a family with LMNA and EMD mutations: Role of
      digenic mechanism?
AB  - BACKGROUND: Mutations in the EMD and LMNA genes, encoding emerin and lamins A and
      C, are responsible for the X-linked and autosomal dominant and recessive forms of
      Emery-Dreifuss muscular dystrophy (EDMD). LMNA mutations can also lead to several
      other disorders, collectively termed laminopathies, involving heart, fat, nerve,
      bone, and skin tissues, and some premature ageing syndromes. METHODS: Fourteen
      members of a single family underwent neurologic, electromyographic, and
      cardiologic assessment. Gene mutation and protein expression analyses were
      performed for lamins A/C and emerin. RESULTS: Clinical investigations showed
      various phenotypes, including isolated cardiac disease (seven patients), axonal
      neuropathy (one patient), and a combination of EDMD with axonal neuropathy (two
      patients), whereas five subjects remained asymptomatic. Genetic analyses
      identified the coincidence of a previously described homozygous LMNA mutation
      (c.892C-->T, p. R298C) and a new in-frame EMD deletion (c.110-112delAGA, p.
      delK37), which segregate independently. Analyses of the contribution of these
      mutations showed 1) the EMD codon deletion acts in X-linked dominant fashion and
      was sufficient to induce the cardiac disease, 2) the combination of both the
      hemizygous EMD and the homozygous LMNA mutations was necessary to induce the EDMD
      phenotype, 3) emerin was present in reduced amount in EMD-mutated cells, and 4)
      lamin A/C and emerin expression was most dramatically affected in the doubly
      mutated fibroblasts. CONCLUSIONS: This highlights the crucial role of lamin A/C
      emerin interactions, with evidence for synergistic effects of these mutations
      that lead to Emery-Dreifuss muscular dystrophy as the worsened result of digenic
      mechanism in this family.

PMID- 17536045
TI  - Personality traits distinguishing dementia with Lewy bodies from Alzheimer
      disease.
AB  - OBJECTIVE: To identify personality traits that distinguish dementia with Lewy
      bodies (DLB) from Alzheimer disease (AD). METHODS: We examined 290 participants
      enrolled in a longitudinal study (nondemented control = 34, DLB = 128, AD = 128)
      followed to autopsy. As part of the annual interview with the collateral source,
      the clinician asked about specific changes in personality, interests, and drives
      based on items from the Blessed Dementia Scale (BDS). Statistical analysis was
      performed using chi(2) and Fisher exact tests. Factor analysis was performed to
      determine underlying structure and receiver operating characteristic curves
      assessed the ability for each of three derived factors to discriminate DLB from
      AD. RESULTS: The sample was evaluated for a mean of 4.8 visits (range 1 to 14)
      with a mean age of 77.6 +/- 9.9 years. The participants' cognitive status ranged
      from nondemented (Clinical Dementia Rating [CDR] 0) through all stages of
      dementia (CDR > or = 0.5). Personality traits that distinguished DLB included
      diminished emotional responsiveness (p = 0.004), relinquishing hobbies (p =
      0.01), growing apathy (p = 0.03), and purposeless hyperactivity (p = 0.003).
      Factor analyses of the BDS revealed a PASSIVE factor (diminished emotional
      responsiveness, relinquished hobbies, growing apathy, and purposeless
      hyperactivity) explaining 10.4% of variance and that DLB was more likely to
      manifest these personality traits than AD (p = 0.001). The PASSIVE factor
      discriminated DLB from AD (area under the curve = 0.61, 95% CI: 0.54 to 0.68, p =
      0.006). Any change in personality is associated with the presence of visual
      hallucinations. CONCLUSIONS: Our results suggest that incorporating a brief,
      simple inventory of personality traits may improve the identification of
      individuals with dementia with Lewy bodies.

PMID- 17536046
TI  - Inflammatory markers and the risk of Alzheimer disease: the Framingham Study.
AB  - OBJECTIVE: To examine whether serum cytokines and spontaneous production of
      peripheral blood mononuclear cell (PBMC) cytokines are associated with the risk
      of incident Alzheimer disease (AD). METHODS: We followed 691 cognitively intact
      community-dwelling participants (mean age 79 years, 62% women) and related PBMC
      cytokine production (tertiles of spontaneous production of interleukin 1 [IL-1],
      IL-1 receptor antagonist, and tumor necrosis factor alpha [TNF-alpha]) and serum
      C-reactive protein and interleukin 6 (IL-6) to the risk of incident AD. RESULTS:
      Adjusting for clinical covariates, individuals in the top two tertiles (T2 and
      T3) of PBMC production of IL-1 or the top tertile (T3) of PBMC production of TNF
      alpha were at increased risk of developing AD (multivariable-adjusted hazard
      ratio [HR] for IL-1 T2 = 2.84, 95% CI 1.09 to 7.43; p = 0.03 and T3 = 2.61, 95%
      CI 0.96 to 7.07; p = 0.06; for TNF-alpha, adjusted HR for T2 = 1.30, 95% CI 0.53
      to 3.17; p = 0.57 and T3 = 2.59, 95% CI 1.09 to 6.12; p = 0.031]) compared with
      those in the lowest tertile (T1). INTERPRETATION: Higher spontaneous production
      of interleukin 1 or tumor necrosis factor alpha by peripheral blood mononuclear
      cells may be a marker of future risk of Alzheimer disease (AD) in older
      individuals. These data strengthen the evidence for a pathophysiologic role of
      inflammation in the development of clinical AD.

PMID- 17536047
TI  - CIND and MCI in the Italian elderly: frequency, vascular risk factors,
      progression to dementia.
AB  - OBJECTIVE: To estimate prevalence and progression to dementia of cognitive
      impairment, no dementia (CIND), mild cognitive impairment (MCI), and relative
      subtypes, evaluating the relationships with daily functioning, cardiovascular
      diseases and vascular risk factors. METHODS: We evaluated CIND and MCI in the
      Italian Longitudinal Study on Aging. The neuropsychological battery assessed
      global cognitive function, memory and attention. Two thousand eight hundred
      thirty participants were examined at baseline and after a mean follow-up of 3.9
      +/- 0.7 years. RESULTS: The prevalence was 9.5% for CIND and 16.1% for MCI.
      Prevalence rates for CIND subtypes were 1.8% for amnestic, 2.3% for single
      nonmemory, 1.5% for multidomain, and 3.9% for CIND defined only on global
      cognitive function. The prevalence was 7.0% for amnestic, 7.8% for single
      nonmemory, and 1.3% for multidomain MCI. Incidence of dementia (per 1,000 person
      years) was 7.63 in the total sample, 21.37 in CIND, and 13.59 in MCI. In MCI,
      rates ranged from 8.74 in amnestic to 40.60 in multidomain subtype. The highest
      incidence of 56.02 per 1,000 person-years was found in multidomain CIND. Both
      CIND and MCI increased by almost three times the risk of dementia at follow-up.
      Among baseline variables, only previous stroke and impairment in instrumental
      activities of daily living significantly increased the risk of dementia at follow
      up. CONCLUSIONS: Both cognitive impairment, no dementia and mild cognitive
      impairment are frequent in the Italian elderly (2,955,000 prevalent cases
      expected) and significantly predict progression to dementia. Individuation of
      subgroups with different risk factors and transition rates to dementia is
      required to plan early and cost-effective interventions.

PMID- 17536048
TI  - Autoimmune autonomic ganglionopathy: IgG effects on ganglionic acetylcholine
      receptor current.
AB  - BACKGROUND: Autoimmune autonomic ganglionopathy (AAG) is an acquired immune
      mediated form of diffuse autonomic failure. Many patients have serum antibodies
      that bind to the ganglionic acetylcholine receptors (AChRs) that mediate fast
      synaptic transmission in autonomic ganglia. Previous clinical studies and
      observations in animal models suggest that AAG is an antibody-mediated neurologic
      disorder. METHODS: Using whole-cell patch clamp techniques, we recorded
      ganglionic AChR currents in cultured human IMR-32 cells and examined the effects
      of bath application of IgG derived from patients with AAG. RESULTS: IgG from
      seven patients with AAG all produced a progressive decline in whole-cell
      ganglionic AChR current, whereas IgG from control subjects had no effect. The
      effect was abolished at low temperature. Fab antibody fragments had no effect
      unless a secondary antibody was added concurrently. IgG from one patient also
      produced a more immediate reduction of ganglionic AChR current. CONCLUSIONS: The
      characteristics of antibody-mediated inhibition of ganglionic acetylcholine
      receptor (AChR) current are consistent with modulation and blocking of the
      membrane AChR, analogous to the effects of muscle AChR antibodies in myasthenia
      gravis. Our observations demonstrate that antibodies in patients with autoimmune
      autonomic ganglionopathy (AAG) cause physiologic changes in ganglionic AChR
      function and confirm that AAG is an antibody-mediated disorder.

PMID- 17536049
TI  - Optokinetic therapy improves text reading in patients with hemianopic alexia: a
      controlled trial.
AB  - OBJECTIVE: An acquired right-sided homonymous hemianopia can result in slowed
      left-to-right text reading, called hemianopic alexia (HA). Patients with HA lack
      essential visual information to help guide ensuing reading fixations. We tested
      two hypotheses: first, that practice with a visual rehabilitation method that
      induced small-field optokinetic nystagmus (OKN) would improve reading speeds in
      patients with HA when compared to a sham visual rehabilitation therapy; second,
      that this therapy would preferentially affect reading saccades into the blind
      field. METHODS: Nineteen patients with HA were entered into a two-armed study
      with two therapy blocks in each arm: one group practiced reading moving text (MT)
      that scrolled from right to left daily for two 4-week blocks (Group1), while the
      other had sham therapy (spot the difference) for the first block and then crossed
      over to MT for the second. RESULTS: Group 1 showed significant improvements in
      static text reading speed over both therapy blocks (18% improvement), while Group
      2 did not significantly improve over the first block (5% improvement) but did
      when they crossed over to the MT block (23% improvement). MT therapy was
      associated with a direction-specific effect on saccadic amplitude for rightward
      but not leftward reading saccades. CONCLUSION: Optokinetic nystagmus inducing
      therapy preferentially affects reading saccades in the direction of the induced
      (involuntary) saccadic component. This is the first study to demonstrate the
      effectiveness of a specific eye movement based therapy in patients with
      hemianopic alexia (HA) in the context of a therapy-controlled trial. A free Web
      based version of the therapy used in this study is available online to suitable
      patients with HA.

PMID- 17536050
TI  - Adiponectin levels in patients with intracranial atherosclerosis.
AB  - BACKGROUND: Adiponectin is a protein secreted by adipose cells that improves
      insulin sensitivity and possesses antiatherogenic properties. In this study, we
      investigated the relationship between adiponectin levels and ischemic stroke
      subtype. METHODS: Using clinical, imaging, and laboratory data, 231 consecutive
      patients admitted to a university medical center over a 2-year period with acute
      cerebral infarcts were categorized into four subtypes: intracranial
      atherosclerosis (n = 67), extracranial atherosclerosis (n = 61), small arterial
      occlusion (n = 63), and cardioembolic (n = 40). Clinical features, risk factors
      including the presence of metabolic syndrome, and levels of s-adiponectin were
      compared between groups. RESULTS: Patients with more severe metabolic
      abnormalities were more likely to have lower s-adiponectin levels (p = 0.002). S
      adiponectin levels differed by stroke subtype: highest in the cardioembolic group
      and lowest in the intracranial atherosclerosis group (8.42 +/- 5.07 vs 5.60 +/-
      2.79 microg/mL, p = 0.01). Extracranial atherosclerosis (6.45 +/- 4.10 microg/mL)
      and small arterial occlusion (6.07 +/- 3.44 microg/mL) groups were intermediate.
      Patients with advanced intracranial atherosclerosis (> or =1 additional lesion
      outside the symptomatic arterial territory) had lower s-adiponectin levels than
      those with isolated intracranial atherosclerosis (4.95 +/- 2.63 vs 6.13 +/- 2.84
      microg/mL, p = 0.003). In multiple regression analysis, s-adiponectin levels, but
      not metabolic syndrome, were independently associated with intracranial
      atherosclerosis. CONCLUSIONS: Symptomatic intracranial atherosclerosis is
      associated with lower s-adiponectin levels vs other ischemic stroke subtypes.

PMID- 17536051
TI  - The cost of pneumonia after acute stroke.
AB  - OBJECTIVE: To determine the incremental costs of pneumonia occurring during
      hospitalization for stroke. METHODS: We reviewed hospital records of all Medicare
      patients admitted for ischemic or hemorrhagic stroke to 29 hospitals in a large
      metropolitan area, 1991 through 1997, excluding those who died or had do not
      resuscitate orders written within 3 days of admission. Hospital costs of patients
      with stroke were determined using Medicare Provider Analysis and Review data
      after adjustment for baseline factors affecting cost and propensity for
      pneumonia. Secondary analyses examined the risk-adjusted relationship of
      pneumonia to discharge disposition. RESULTS: Pneumonia occurred in 5.6%
      (635/11,286) of patients with stroke, and was more common among patients admitted
      from nursing homes and those with greater severity of illness (p < 0.001). Mean
      adjusted costs of hospitalization for patients with stroke with pneumonia were
      $21,043 (95% CI $19,698 to 22,387) and were $6,206 (95% CI $6,150 to 6,262) for
      patients without pneumonia, resulting in an incremental cost of $14,836 (95% CI
      $14,436 to 15,236). Patients with pneumonia were over 70% more likely to be
      discharged with requirements for extended care (adjusted OR 1.73, 95% CI 1.32 to
      2.26). CONCLUSION: Extrapolated to the over 500,000 similar patients hospitalized
      for stroke in the United States, the annual cost of pneumonia as a complication
      after acute stroke is approximately $459 million.

PMID- 17536052
TI  - A controlled study of reverse transcriptase in serum and CSF of HIV-negative
      patients with ALS.
AB  - Reverse transcriptase has been detected in the serum of HIV-negative patients
      with amyotrophic lateral sclerosis (ALS). An ALS-like disorder in HIV-positive
      patients can remit with antiretroviral therapy. Using the product enhanced assay
      technique, we measured reverse transcriptase activity in the serum and CSF of 23
      HIV-negative patients with ALS and 21 neurologic disease controls. Results for
      CSF were not significant, whereas reverse transcriptase was detected in 56% of
      ALS sera vs 19% of controls.

PMID- 17536053
TI  - Hyperekplexia caused by dominant-negative suppression of glyra1 function.

PMID- 17536054
TI  - Spontaneous tibialis anterior tendon rupture: a rare cause of foot drop.

PMID- 17536055
TI  - Mutations in VAPB are not associated with sporadic ALS.

PMID- 17536056
TI  - Armored brain.

PMID- 17536057
TI  - January 16 highlight and commentary: subspecialization within somatosensory
      cortex.

PMID- 17536058
TI  - Vertebral artery hypoplasia: a predisposing factor for posterior circulation
      stroke?

PMID- 17536059
TI  - Using tPA for acute stroke in a rural setting.

PMID- 17536060
TI  - Two randomized vitamin D trials in ambulatory patients on anticonvulsants: impact
      on bone.

PMID- 17536061
TI  - Major ongoing stroke trials.

PMID- 17536062
TI  - Peroxisome proliferator activated receptor alpha/gamma dual agonist tesaglitazar
      attenuates diabetic nephropathy in db/db mice.
AB  - Peroxisome proliferator-activated receptors (PPARs) are nuclear transcription
      factors and play a central role in insulin sensitivity, lipid metabolism, and
      inflammation. Both PPARalpha and -gamma are expressed in the kidney, and their
      agonists exhibit renoprotective effects in type 2 diabetes. In the present
      studies, we investigated the effect of the PPARalpha/gamma dual agonist
      tesaglitazar on diabetic nephropathy in type 2 diabetic db/db mice. Treatment of
      db/db mice with tesaglitazar for 3 months significantly lowered fasting plasma
      glucose and homeostasis model assessment of insulin resistance levels but had
      little effect on body weight, adiposity, or cardiac function. Treatment with
      tesaglitazar was associated with reduced plasma insulin and total triglyceride
      levels and increased plasma adiponectin levels. Notably, tesaglitazar markedly
      attenuated albuminuria and significantly lowered glomerulofibrosis, collagen
      deposition, and transforming growth factor-beta1 expression in renal tissues of
      db/db mice. In cultured mesangial cells and proximal tubule cells, where both
      PPARalpha and -gamma were expressed, tesaglitazar treatment abolished high
      glucose-induced total collagen protein production and type I and IV collagen gene
      expression. Collectively, tesaglitazar treatment not only improved insulin
      resistance, glycemic control, and lipid profile but also markedly attenuated
      albuminuria and renal glomerular fibrosis in db/db mice. These findings support
      the utility of dual PPARalpha/gamma agonists in treating type 2 diabetes and
      diabetic nephropathy.

PMID- 17536063
TI  - Effects of physical activity and weight loss on skeletal muscle mitochondria and
      relationship with glucose control in type 2 diabetes.
AB  - OBJECTIVE: Reduced mitochondrial capacity in skeletal muscle occurs in type 2
      diabetic patients and in those at increased risk for this disorder, but the
      extent to which mitochondrial dysfunction in type 2 diabetic patients is
      remediable by physical activity and weight loss intervention is uncertain. We
      sought to address whether an intervention of daily moderate-intensity exercise
      combined with moderate weight loss can increase skeletal muscle mitochondrial
      content in type 2 diabetic patients and to address the relationship with
      amelioration of insulin resistance and hyperglycemia. RESEARCH DESIGN AND
      METHODS: Muscle biopsies were obtained before and after a 4-month intervention to
      assess mitochondrial morphology, mitochondrial DNA content, and mitochondrial
      enzyme activities. Glucose control, body composition, aerobic fitness, and
      insulin sensitivity were measured. RESULTS: In response to a weight loss of 7.1
      +/- 0.8% and a 12 +/- 1.6% improvement in Vo(2max) (P < 0.05), insulin
      sensitivity improved by 59 +/- 21% (P < 0.05). There were significant increases
      in skeletal muscle mitochondrial density (by 67 +/- 17%, P < 0.01), cardiolipin
      content (55 +/- 17%, P < 0.01), and mitochondrial oxidation enzymes. Energy
      expenditure during physical activity correlated with the degree of improvement in
      insulin sensitivity (r = 0.84, P < 0.01), and, in turn, improvement in
      mitochondrial content was a strong correlate of intervention-induced improvement
      in A1C and fasting plasma glucose. CONCLUSIONS: Intensive short-term lifestyle
      modifications can restore mitochondrial content and functional capacity in
      skeletal muscle in type 2 diabetic patients. The improvement in the oxidative
      capacity of skeletal muscle may be a key component mediating salutary effects of
      lifestyle interventions on hyperglycemia and insulin resistance.

PMID- 17536064
TI  - Podocyte detachment and reduced glomerular capillary endothelial fenestration in
      human type 1 diabetic nephropathy.
AB  - The aim of this study was to investigate the structural characteristics of
      podocytes and endothelial cells in diabetic nephropathy. We studied 18 patients
      with type 1 diabetes (seven normoalbuminuric, six microalbuminuric, and five
      proteinuric), and six normal control subjects. Groups were not different for age.
      Type 1 diabetic groups were not different for diabetes duration or age at
      diabetes onset. Podocyte foot process width (FPW), fraction of glomerular
      basement membrane (GBM) surface with intact nondetached foot processes (IFP),
      fraction of glomerular capillary luminal surface covered by fenestrated
      endothelium [S(S)(Fenestrated/cap)] and classic diabetic glomerulopathy lesions
      were morphometrically measured. Albumin excretion (AER) and glomerular filtration
      (GFR) rates were also measured. GFR correlated inversely and AER directly with
      GBM and mesangial measurements in diabetic patients. FPW correlated inversely
      with GFR (r = -0.71, P = 0.001) and directly with AER (r = 0.66, P = 0.003), GBM,
      and mesangial parameters. The GBM fraction covered by IFP was decreased in
      proteinuric versus control subjects (P = 0.001), normoalbuminuric patients (P =
      0.0002) and microalbuminuric patients (P = 0.04) and correlated with renal
      structural and functional parameters, including AER (r = -0.52, P = 0.03). Only
      78% of GBM was covered by IFP in proteinuric patients. S(S)(Fenestrated/cap) was
      reduced in normoalbuminuric (P = 0.03), microalbuminuric (P = 0.03), and
      proteinuric (P = 0.002) patients versus control subjects. S(S)(Fenestrated/cap)
      correlated with mesangial fractional volume per glomerulus (r = -0.57, P = 0.01),
      IFP (r = 0.61, P = 0.007), and FPW (r = -0.58, P = 0.01). These novel studies
      document that podocyte detachment and diminished endothelial cell fenestration
      are related to classical diabetic nephropathy lesions and renal function in type
      1 diabetic patients and support a need for further studies of podocyte/GBM
      adherence and podocyte/endothelial cell functional interactions in diabetic
      nephropathy.

PMID- 17536065
TI  - Proteolytic degradation of VE-cadherin alters the blood-retinal barrier in
      diabetes.
AB  - OBJECTIVE: Increased vascular permeability due to alteration of the blood-retinal
      barrier (BRB) is one of the major complications in early diabetes. The aim of the
      present study was to determine whether diabetes alters the cellular expression
      and distribution of the adherens junction protein vascular endothelial (VE)
      cadherin in retinal endothelial cells and if this alteration is mediated by
      proteinase activity. RESEARCH DESIGN AND METHODS: Diabetes was induced in Brown
      Norway rats using streptozotocin, and retinal vascular permeability was measured
      by the Evans blue technique. The expression of matrix metalloproteinases (MMPs)
      and VE-cadherin was examined in isolated retinal vessels or cultured endothelial
      cells in response to diabetes and advanced glycation end products (AGEs). The
      cleavage of VE-cadherin from the endothelial cell surface was monitored by
      Western blotting following MMP or AGE treatment. RESULTS: Retinal vascular
      permeability was significantly increased in rats following 2 weeks of diabetes
      coincident with a decrease of VE-cadherin expression. This increased vascular
      permeability could be inhibited with an MMP inhibitor. Treatment of endothelial
      cells with AGE-BSA led to a reduction of VE-cadherin staining on the cell surface
      and increased permeability, which was MMP mediated. Treatment of cells with
      specific MMPs or AGEs resulted in cleavage of VE-cadherin from the cell surface.
      CONCLUSIONS: These observations suggest a possible mechanism by which diabetes
      contributes to BRB breakdown through proteolytic degradation of VE-cadherin. This
      may indicate a role for extracellular proteinases in alteration of the BRB seen
      in diabetic retinopathy.

PMID- 17536066
TI  - The SUMO conjugating enzyme Ubc9 is a regulator of GLUT4 turnover and targeting
      to the insulin-responsive storage compartment in 3T3-L1 adipocytes.
AB  - The small ubiquitin-related modifier (SUMO) conjugating enzyme Ubc9 has been
      shown to upregulate GLUT4 in L6 myoblast cells, although the mechanism of action
      has remained undefined. Here we investigated the physiological significance of
      Ubc9 in GLUT4 turnover and subcellular targeting by adenovirus vector-mediated
      overexpression and by small interfering RNA (siRNA)-mediated gene silencing of
      Ubc9 in 3T3-L1 adipocytes. Overexpression of Ubc9 resulted in an inhibition of
      GLUT4 degradation and promoted its targeting to the unique insulin-responsive
      GLUT4 storage compartment (GSC), leading to an increase in GLUT4 amount and
      insulin-responsive glucose transport in 3T3-L1 adipocytes. Overexpression of Ubc9
      also antagonized GLUT4 downregulation and its selective loss in GSC induced by
      long-term insulin stimulation. By contrast, siRNA-mediated depletion of Ubc9
      accelerated GLUT4 degradation and decreased the amount of the transporter,
      concurrent with its selective loss in GSC, which resulted in attenuated insulin
      responsive glucose transport. Intriguingly, overexpression of the catalytically
      inactive mutant Ubc9-C93A produced effects indistinguishable from those with wild
      type Ubc9, suggesting that Ubc9 regulates GLUT4 turnover and targeting to GSC by
      a mechanism independent of its catalytic activity. Thus, Ubc9 is a pivotal
      regulator of the insulin sensitivity of glucose transport in adipocytes.

PMID- 17536068
TI  - Role of insulin resistance in predicting progression to type 1 diabetes.
AB  - OBJECTIVE: The purpose of this study was to determine whether insulin resistance
      is a risk factor for the development of type 1 diabetes in autoantibody-positive
      first-degree relatives of diabetic family members. RESEARCH DESIGN AND METHODS:
      Subjects (n = 186) who had a projected 25-50% risk for diabetes and subjects (n =
      170) who had a projected >50% risk for type 1 diabetes in 5 years were followed
      until clinical diabetes onset or the end of the study as part of the Diabetes
      Prevention Trial-Type 1. We assessed insulin secretion with the first-phase
      insulin response (FPIR) and insulin resistance with homeostasis model assessment
      of insulin resistance (HOMA-IR) from an intravenous glucose tolerance test. The
      median follow-up was 4.3 years for moderate-risk subjects and 3.7 years for high
      risk subjects. RESULTS: During the follow-up period, 53 subjects in the moderate
      risk group and 70 subjects in the high-risk group developed type 1 diabetes.
      After adjustments for confounders using multivariate analysis, HOMA-IR and the
      FPIR-to-HOMA-IR ratio were significantly associated with type 1 diabetes in both
      risk groups. In the moderate-risk population, the hazard ratio (HR) of HOMA-IR
      was 2.70 (95% CI 1.45-5.06) and the HR of FPIR-to-HOMA-IR was 0.32 (95% CI 0.18
      0.57). In the high-risk population, the HR of HOMA-IR was 1.83 (95% CI 1.19-2.82)
      and the HR of FPIR-to-HOMA-IR was 0.56 (95% CI 0.40-0.78). CONCLUSIONS: There is
      clear evidence of the association between insulin resistance and progression to
      type 1 diabetes. The combination of FPIR and HOMA-IR could be used as a better
      metabolic indicator for type 1 diabetes risk for prediction and suggests possible
      intervention strategies for diabetes prevention.

PMID- 17536067
TI  - Depression, self-care, and medication adherence in type 2 diabetes: relationships
      across the full range of symptom severity.
AB  - OBJECTIVE: We examined the association between depression, measured as either a
      continuous symptom severity score or a clinical disorder variable, with self-care
      behaviors in type 2 diabetes. RESEARCH DESIGN AND METHODS: We surveyed 879 type 2
      diabetic patients from two primary care clinics using the Harvard Department of
      Psychiatry/National Depression Screening Day Scale (HANDS), the Summary of
      Diabetes Self-Care Activities, and self-reported medication adherence. RESULTS:
      Of the patients, 19% met the criteria for probable major depression (HANDS score
      >or=9), and an additional 66.5% reported at least some depressive symptoms. After
      controlling for covariates, patients with probable major depression reported
      significantly fewer days' adherent to diet, exercise, and glucose self-monitoring
      regimens (P < 0.01) and 2.3-fold increased odds of missing medication doses in
      the previous week (95% CI 1.5-3.6, P < 0.001) compared with all other
      respondents. Continuous depressive symptom severity scores were better predictors
      of nonadherence to diet, exercise, and medications than categorically defined
      probable major depression. Major depression was a better predictor of glucose
      monitoring. Among the two-thirds of patients not meeting the criteria for major
      depression (HANDS score <9, n = 709), increasing HANDS scores were incrementally
      associated with poorer self-care behaviors (P < 0.01). CONCLUSIONS: These
      findings challenge the conceptualization of depression as a categorical risk
      factor for nonadherence and suggest that even low levels of depressive
      symptomatology are associated with nonadherence to important aspects of diabetes
      self-care. Interventions aimed at alleviating depressive symptoms, which are
      quite common, could result in significant improvements in diabetes self-care.

PMID- 17536069
TI  - Increase in physical activity energy expenditure is associated with reduced
      metabolic risk independent of change in fatness and fitness.
AB  - OBJECTIVE: We sought to examine whether change in physical activity energy
      expenditure (PAEE) is associated with change in metabolic risk factors and
      whether this association is independent of change in fat mass and aerobic
      fitness. RESEARCH DESIGN AND METHODS: In a population-based sample of 176 men and
      217 women followed prospectively for 5.6 years, we measured PAEE by individually
      calibrated heart rate monitoring, aerobic fitness, total body fat (fat mass), and
      metabolic risk factors (blood pressure, fasting triglycerides, HDL cholesterol,
      insulin, and 2-h glucose) at baseline and follow-up. RESULTS: A 100 J x kg fat
      free mass (FFM)(-1) x min(-1) increase in PAEE from baseline to follow-up reduced
      triglycerides by 3.5% (95% CI 0.03-5.7) in men and 3.2% (0.02-5.4) in women,
      fasting insulin by 5.3% (1.0-7.5) in men and women, and 2-h glucose by 3.2% (0.3
      5.3) in men and 3.1% (0.3-5.2) in women, after adjustment for sex, age, smoking
      status, aerobic fitness, baseline phenotype, and change in fat mass. In general,
      the magnitudes of association for change in fat mass with metabolic risk factors
      were two to three times stronger than for PAEE. CONCLUSIONS: Increasing levels of
      physical activity may protect against metabolic disease even in the absence of
      improved aerobic fitness and reduced body fatness. Therefore, the combination of
      increasing levels of physical activity and avoidance of gain in fat mass is
      likely to be the most successful approach for preventing cardiovascular and
      metabolic disease.

PMID- 17536070
TI  - Insulin resistance syndrome in the elderly: assessment of functional,
      biochemical, metabolic, and inflammatory status.
AB  - OBJECTIVE: Hyperinsulinemic euglycemia, or insulin resistance syndrome (IRS), is
      associated with increased morbidity and mortality. Although thought to be
      associated with proinflammatory states, little work has been done in this area.
      Here, we determined the impact of IRS on functional, biochemical, metabolic, and
      inflammatory status in a high-risk population: elderly women in nursing homes.
      RESEARCH DESIGN AND METHODS: Functional, biochemical, metabolic, and inflammatory
      parameters were measured in 100 consecutive ambulatory, elderly women who resided
      in nursing homes. Diabetic subjects and residents with fasting blood glucose
      >or=110 mg/dl were excluded. Remaining residents were classified as insulin
      resistant (IR) (insulin >100 pmol/l) or non-IR (NIR). RESULTS: A total of 16
      residents were IR and 53 NIR. No differences in functional status, BMI, renal
      function, C-reactive protein, or immune cell levels were found. Fasting blood
      glucose was higher in IR subjects ([means +/- SD] 94.1 +/- 8.1 vs. 87.9 +/- 8.2,
      P < 0.05), indicating a very mild glucose intolerance. Serum C-peptide (P <
      0.05), amylin (P < 0.01), and leptin (P < 0.01), but not adiponectin or resistin,
      were higher in IR subjects. Higher leptin-to-BMI and insulin-to-C-peptide ratios
      suggested an increased percent body fat mass and altered clearance of insulin,
      respectively. Eleven of 13 cytokines had arithmetic elevations, but only tumor
      necrosis factor-alpha (TNF) reached statistical significance (P < 0.01). TNF and
      insulin levels were highly correlated. CONCLUSIONS: IRS in the healthiest of long
      term care residents is relatively rare but is associated with mild glucose
      intolerance, increased percent body fat, altered insulin clearance, and a
      proinflammatory status as evidenced by an elevated TNF.

PMID- 17536071
TI  - Increased body iron stores of obese women with polycystic ovary syndrome are a
      consequence of insulin resistance and hyperinsulinism and are not a result of
      reduced menstrual losses.
AB  - OBJECTIVE: Increased serum ferritin levels, indicating increased body iron
      stores, have been found in overweight and obese women with polycystic ovary
      syndrome (PCOS). This finding might result from reduced menstrual losses
      secondary to oligo- or amenorrhea or from hyperinsulinism secondary to insulin
      resistance, because insulin favors the intestinal absorption and the tissue
      deposition of iron. To explore which of these mechanisms is responsible for the
      increase in body iron stores in women with PCOS, we have monitored the changes in
      serum ferritin levels during treatment with an antiandrogenic oral contraceptive
      or an insulin sensitizer. RESEARCH DESIGN AND METHODS: Thirty-four consecutive
      PCOS patients were randomized to an oral contraceptive containing 35 microg
      ethinyl-estradiol plus 2 mg cyproterone acetate (Diane(35) Diario) or metformin
      (850 mg twice daily), and their serum ferritin levels were evaluated at baseline
      and after 12 and 24 weeks of treatment. RESULTS: Despite the fact that treatment
      with Diane(35) Diario restored regular menstrual cycles in all the patients,
      whereas metformin only did so in 50% of them, serum ferritin levels decreased at
      12 and 24 weeks of treatment only with metformin, in association with a marked
      increase in insulin sensitivity. On the contrary, no changes in ferritin and
      insulin sensitivity were observed with Diane(35) Diario. CONCLUSIONS: Our present
      results suggest that insulin resistance and hyperinsulinism, and not the reduced
      menstrual losses secondary to from oligo- or amenorrhea, are responsible of the
      increased ferritin levels and body iron stores found in overweight and obese
      women with PCOS.

PMID- 17536072
TI  - Microvascular diabetes complications in Wolfram syndrome (diabetes insipidus,
      diabetes mellitus, optic atrophy, and deafness [DIDMOAD]): an age- and duration
      matched comparison with common type 1 diabetes.
AB  - OBJECTIVE: Some previous studies suggested that patients suffering from Wolfram
      syndrome or DIDMOAD (diabetes insipidus, diabetes mellitus, optic atrophy, and
      deafness) might be relatively preserved from diabetic retinopathy and
      nephropathy. However, these data were not conclusive because either observations
      were only anecdotic or did not match with control type 1 diabetic populations.
      RESEARCH DESIGN AND METHODS: A group of 26 French diabetic patients with DIDMOAD
      was compared with a population of 52 patients with common type 1 diabetes matched
      for age at diabetes diagnosis (8.62 +/- 1.84 vs. 8.27 +/- 1.30 years; P = NS) and
      diabetes duration (12.88 +/- 1.58 vs. 12.87 +/- 1.13 years; P = NS) to study the
      quality of glycemic control and the incidence of microvascular complications.
      RESULTS: Glycemic control was significantly better in the DIDMOAD group than in
      the type 1 diabetic group (A1C: 7.72 +/- 0.21 vs. 8.99 +/- 0.25%, respectively; P
      = 0.002), with significant lower daily insulin requirements (0.71 +/- 0.07 vs.
      0.88 +/- 0.04 UI x kg(-1) x day(-1), respectively; P = 0.0325). The prevalence of
      microvascular complications in the DIDMOAD group was half that observed in the
      type 1 diabetic group, but the difference was not significant. CONCLUSIONS:
      Diabetes in DIDMOAD patients is more easily controlled despite the presence of
      other handicaps. This better glycemic control could explain the trend to
      decreased microvascular diabetes complications observed in previous studies.

PMID- 17536073
TI  - Intrauterine growth retardation, insulin resistance, and nonalcoholic fatty liver
      disease in children.

PMID- 17536074
TI  - Thiazolidinediones and heart failure: a teleo-analysis.
AB  - OBJECTIVE: Thiazolidinediones (TZDs) are known to increase the risk of heart
      failure in patients with type 2 diabetes. We aimed to evaluate the magnitude of
      the risk of heart failure with TZDs and classify this adverse effect under the
      novel dose-time-susceptibility system. RESEARCH DESIGN AND METHODS: Evidence from
      randomized trials, controlled observational studies, anecdotal case reports, case
      series, and spontaneous reports in the Canadian Drug Reaction Monitoring Program
      (CADRMP) was analyzed in a teleo-analysis. RESULTS: A random-effects meta
      analysis of three randomized controlled trials showed an odds ratio (OR) of 2.1
      (95% CI 1.08-4.08; P = 0.03) for the risk of heart failure in patients randomized
      to TZDs compared with placebo. Four observational studies revealed an OR of 1.55
      (1.33-1.80; P < 0.00001) for heart failure with TZDs. A dose-time-susceptibility
      analysis of 28 published reports and 214 spontaneous reports from the CADRMP
      database showed that heart failure was more likely to occur after several months
      (with median treatment duration of 24 weeks after initiation of therapy). Heart
      failure equally occurred at high and low doses. The adverse reaction was not
      limited to the elderly, with 42 of 162 (26%) of the reported cases occurring in
      patients aged <60 years. CONCLUSIONS: Our teleo-analysis confirms the increased
      magnitude of the risk of heart failure with TZDs. We estimate the number needed
      to harm with TZDs to be approximately 50 over 2.2 years. Existing guidelines and
      package inserts may have to be revised to incorporate these risk characteristics
      of TZDs.

PMID- 17536075
TI  - Walking to work is an independent predictor of incidence of type 2 diabetes in
      Japanese men: the Kansai Healthcare Study.

PMID- 17536076
TI  - Population-based incidence of type 2 diabetes in northern Spain: the Asturias
      Study.
AB  - OBJECTIVE: The aim of this study was to define the incidence of type 2 diabetes
      in a low-risk Caucasian population in northern Spain and its association with
      various risk factors. RESEARCH DESIGN AND METHODS: The Asturias Study is a
      prospective, population-based survey of diabetes and cardiovascular risk factors.
      The baseline examination was carried out during 1998-1999 when 1,034 individuals,
      aged 30-75 years, were randomly selected to determine the prevalence of type 2
      diabetes and pre-diabetes in the Principality of Asturias (northern Spain). In
      2004-2005, these same subjects were invited for a follow-up examination; 700
      participated. This study includes only those individuals who did not have
      diabetes at baseline. We used the World Health Organization 1999 criteria to
      classify glucose metabolism at both baseline and follow-up. RESULTS: The
      incidence of diabetes adjusted for the age and sex structure of Asturias was 10.8
      cases/1,000 person-years (95% CI 8.1-14.8). The incidence rates were 5
      cases/1,000 person-years in individuals with normoglycemia, 21 cases/1,000 person
      years in individuals with isolated impaired glucose tolerance (IGT), 34.7
      cases/1,000 person-years in individuals with isolated impaired fasting glucose
      (IFG), and 95.2 cases/1,000 person-years in individuals with combined IFG-IGT.
      Stepwise multiple logistic regression analysis showed that, together with fasting
      plasma glucose (FPG) and 2-h plasma glucose, which were the strongest predictors
      of diabetes, triglycerides and BMI were also independently associated with
      progression to diabetes. CONCLUSIONS: In this 6-year prospective population-based
      study, we found an incidence of type 2 diabetes of 10.8 cases/1,000 person-years.
      Both FPG and 2-h plasma glucose were strongly predictive of diabetes, and their
      effect was additive.

PMID- 17536078
TI  - Cardiorespiratory fitness is strongly related to the metabolic syndrome in
      adolescents.

PMID- 17536077
TI  - Differences in A1C by race and ethnicity among patients with impaired glucose
      tolerance in the Diabetes Prevention Program.
AB  - OBJECTIVE: We sought to examine racial and ethnic differences in A1C in
      individuals with impaired glucose tolerance (IGT). RESEARCH DESIGN AND METHODS:
      We studied 3,819 individuals aged > or = 25 years with IGT who were found to be
      eligible to participant in the Diabetes Prevention Program. A1C was compared
      among five racial and ethnic groups before and after adjustment for factors that
      differed among groups or might affect glycemia including age, sex, education,
      marital status, blood pressure, adiposity (BMI and waist circumference),
      hematocrit, fasting and post-glucose load glucose levels, glucose area under the
      curve (AUC), beta-cell function, and insulin resistance. RESULTS: Mean +/- SD A1C
      was 5.91 +/- 0.50%. Among whites, A1C was 5.80 +/- 0.44%, among Hispanics 5.89 +/
      0.46%, among Asian 5.96 +/- 0.45%, among American Indians 5.96 +/- 0.46%, and
      among blacks 6.19 +/- 0.59%. Age, sex, systolic blood pressure, diastolic blood
      pressure, BMI, fasting glucose, glucose AUC, corrected insulin response, and
      insulin resistance were each independent predictors of A1C. Adjusting for these
      and other factors, mean A1C levels were 5.78% for whites, 5.93% for Hispanics,
      6.00% for Asians, 6.12% for American Indians, and 6.18% for blacks (P < 0.001).
      CONCLUSIONS: A1C levels are higher among U.S. racial and ethnic minority groups
      with IGT after adjustment for factors likely to affect glycemia. Among patients
      with IGT, A1C may not be valid for assessing and comparing glycemic control
      across racial and ethnic groups or as an indicator of health care disparities.

PMID- 17536079
TI  - New predictive equations improve monitoring of kidney function in patients with
      diabetes.
AB  - OBJECTIVE: The Cockcroft-Gault and Modification of Diet in Renal Disease (MDRD)
      equations poorly predict glomerular filtration rate (GFR) decline in diabetic
      patients. We sought to discover whether new equations based on serum creatinine
      (the Mayo Clinic Quadratic [MCQ] or reexpressed MDRD equations) or four cystatin
      C-based equations (glomerular filtration rate estimated via cystatin formula [Cys
      eGFR]) were less biased and better predicted GFR changes. RESEARCH DESIGN AND
      METHODS: In 124 diabetic patients with a large range of isotopic GFR (iGFR) (56.1
      +/- 35.3 ml/min per 1.73 m2 [range 5-164]), we compared the performances of the
      equations before and after categorization in GFR tertiles. A total of 20 patients
      had a second determination 2 years later. RESULTS: The Cockcroft-Gault equation
      was the least precise. The MDRD equation was the most precise but the most biased
      according to the Bland-Altman procedure. By contrast with the MDRD and, to a
      lesser extent, the MCQ, three of the four Cys-eGFRs were not biased. All
      equations overestimated the low GFRs, whereas only the MDRD and Rule's Cys-eGFR
      equations underestimated the high GFRs. For the subjects studied twice, iGFR
      changed by -8.5 +/- 17.9 ml/min per 1.73 m2. GFR changes estimated by the
      Cockcroft-Gault (-4.5 +/- 6.8) and MDRD (-5.7 +/- 6.2) equations did not
      correlate with the isotopic changes, whereas new equation-predicted changes did:
      MCQ: -8.7 +/- 9.4 (r = 0.44, P < 0.05) and all four Cys-eGFRs: -6.2 +/- 7.4 to 
      7.3 +/- 8.4 (r = 0.60 to 0.62, all P < 0.005), such as 100/cystatin-C (r = 0.61,
      P < 0.005). CONCLUSIONS: The new predictive equations better estimate GFR than
      the Cockcroft-Gault equation. Although the MDRD equation remains the most
      accurate, it poorly predicts GFR decline, as it overestimates low and
      underestimates high GFRs. This bias is lesser with the MCQ and Cys-eGFR
      equations, so they better predict GFR changes.

PMID- 17536080
TI  - Body weight changes associated with insulin therapy: a retrospective pooled
      analysis of inhaled human insulin (Exubera) versus subcutaneous insulin in five
      controlled Phase III trials.

PMID- 17536081
TI  - Tamoxifen, soy, and lifestyle factors in Asian American women with breast cancer.
AB  - PURPOSE: Soy foods have been a staple in Asia for centuries but the consumption
      of this food in the West is recent. Intake of soy among women at high risk for or
      with breast cancer has become a public health concern because genistein, a major
      component of soy, has weak estrogenic effects on breast epithelium, and has been
      found to negate the benefit of tamoxifen in some animal and in vitro studies.
      PATIENTS AND METHODS: We conducted a cross-sectional study in Asian Americans
      with breast cancer who were tamoxifen users (n = 380) to investigate the
      association between soy intake and circulating levels of tamoxifen and its
      metabolites (N-desmethyl tamoxifen [N-DMT], 4-hydroxytamoxifen [4-OHT], and 4
      hydroxy-N-desmethyl-tamoxifen [endoxifen]). RESULTS: Serum levels of tamoxifen or
      its metabolites were unrelated to self-reported intake of soy or serum levels of
      isoflavones. Blood levels of tamoxifen were 81% higher in postmenopausal women
      age 65 or older compared with premenopausal women age 45 or younger (P = .005);
      similar patterns of results were observed for the tamoxifen metabolites. Levels
      of N-DMT were 27% (P = .03) lower among women in the highest tertile of body mass
      index (BMI, > 24.4 kg/m2) compared with those in the lowest category (BMI 21.5).
      Women who used hypertensive medications had higher levels of tamoxifen (P = .02)
      and N-DMT (P = .04) compared with nonusers. CONCLUSION: We found no evidence that
      soy intake adversely affected levels of tamoxifen or its metabolites. However,
      age, menopausal status, BMI, and use of hypertensive medications significantly
      influenced circulating levels of tamoxifen and its metabolites in this
      population.

PMID- 17536082
TI  - HLA class II expression by Hodgkin Reed-Sternberg cells is an independent
      prognostic factor in classical Hodgkin's lymphoma.
AB  - PURPOSE: The neoplastic Hodgkin Reed-Sternberg (HRS) cells in classical Hodgkin's
      lymphoma (cHL) are derived from B cells. The frequency of HLA class II
      downregulation and its effect on prognosis are unknown. PATIENTS AND METHODS:
      Immunohistochemistry results for HLA class II were evaluated in 292 primary cHL
      patients in a population-based approach. Patients were diagnosed between 1989 and
      2000 in the northern part of the Netherlands. Median age at diagnosis was 38
      years (range, 8 to 88 years); 63% had Ann Arbor stage I or II, 24% stage III, and
      13% stage IV disease. Median follow-up was 7.1 years. For 168 patients, HLA
      genotype data were available. RESULTS: Lack of HLA class II cell-surface
      expression on HRS cells was observed in 41.4% and was more common in patients
      with extranodal disease, patients with Epstein-Barr virus-negative disease, and
      patients with HLA class I-negative HRS cells. Alleles of three microsatellite
      markers in the HLA class II region were associated with presence or absence of
      protein expression. In univariate analyses, lack of HLA class II expression
      coincided with adverse outcome (5-years failure free survival [FFS], 67% v 85%; P
      = .001; 5-years age and sex matched relative survival (RS), 80% v 90%; P = .027).
      This effect remained in multivariate analyses for FFS with a hazard ratio of 2.40
      (95% CI, 1.45 to 3.98) and RS with a relative excess risk of death of 2.55 (95%
      CI, 1.22 to 5.31). CONCLUSION: Lack of membranous HLA class II expression by HRS
      cells in diagnostic lymph node specimens is an independent adverse prognostic
      factor in cHL.

PMID- 17536083
TI  - Assessment of care by breast cancer patients participating or not participating
      in a randomized controlled trial: a report with the Patients' Committee for
      Clinical Trials of the Ligue Nationale Contre le Cancer.
AB  - PURPOSE: Cancer patients participating in randomized controlled trials (RCTs)
      have not been found to have better clinical outcomes than other patients. Our
      objective was to assess the impact of RCTs on patients' satisfaction with care.
      PATIENTS AND METHODS: A prospective study was carried out in a cohort of women
      with breast cancer (N = 455) divided into those invited to participate in an RCT
      (201 acceptances, 66 refusals) and a comparable control group not invited to
      participate (n = 188). All the patients underwent the same treatment
      (fluorouracil, epirubicin, and cyclophosphamide 100 mg/m2 for six cycles). One
      and 7 months after the beginning of chemotherapy, self-administered satisfaction
      scores were used to compare the women's assessment of their care (Comprehensive
      Assessment of Satisfaction with Care validated scale). RESULTS: At the beginning
      of chemotherapy, women to whom RCT had been proposed rated the doctors'
      availability (average +/- standard deviation [SD]: RCT acceptance group, 3.60 +/-
      0.78; RCT refusal group, 3.68 +/- 0.87; control group, 3.41 +/- 0.82; P < or =
      .02) and the doctors' communication (average +/- SD: RCT acceptance group, 3.56
      +/- 0.88; RCT refusal group, 3.67 +/- 0.88; control group, 3.39 +/- 0.84; P .05)
      higher than those to whom the trial was not proposed. After the treatment,
      participants in the RCT felt that their doctor was more supportive (average +/-
      SD: RCT acceptance group, 3.04 +/- 0.92; control group, 2.77 +/- 0.85; P = .005)
      and more informative about their illness and treatment (average +/- SD: RCT
      acceptance group, 3.34 +/- 0.88; control group, 3.08 +/- 0.92; P = .006) than
      those in the control group. The general level of satisfaction was also higher in
      the RCT acceptance group. CONCLUSION: Women participating in an RCT have a more
      positive picture of their doctors' care than others, probably because of the
      structural effects of the informed consent and data collection processes.

PMID- 17536084
TI  - Association between high signal intensity in the posterior disc attachment seen
      on T2 weighted fat-suppressed images and temporomandibular joint pain.
AB  - OBJECTIVES: We sought to determine whether high signal intensity in the posterior
      disc attachment (PDA) seen on T2 weighted fat-suppressed MRI is associated with
      temporomandibular joint (TMJ) pain and joint pathology. METHODS: This study was
      based on 283 TMJs of 177 patients (31 males and 146 females, mean age 32.7 years)
      with TMJ disorders showing anterior disc displacement. MRI evaluation included
      assessment of signal intensity in the PDA and TMJ status (disc displacement with
      reduction, disc displacement without reduction and disc displacement with bone
      changes). Clinical criteria that were considered positive indicators of TMJ pain
      included the presence of pre-auricular pain during palpation, jaw function and
      assisted or unassisted mandibular opening. Association of signal intensity in the
      PDA with joint pain and TMJ status was analysed using chi2 test. RESULTS: Joint
      pain was reported in 47 (77.0%) out of 61 joints with high signal intensity in
      the PDA and in 97 (43.7%) out of 222 joints with low signal intensity in the PDA
      (P<0.0001). High signal intensity in the PDA correlated closely with more
      advanced joint pathology. In joints with anterior disc displacement with bone
      changes, TMJ pain was more commonly reported in joints with high signal intensity
      in the PDA than with low signal intensity in the PDA (P<0.0001). CONCLUSIONS:
      High signal intensity in the PDA on T2 weighted fat-suppressed MRI is associated
      with TMJ pain in TMJ disorders with anterior disc displacement with bone changes
      in the mandibular condyles.

PMID- 17536085
TI  - Cone beam CT and conventional tomography for the detection of morphological
      temporomandibular joint changes.
AB  - OBJECTIVE: To compare the diagnostic accuracy of cone beam CT images with
      conventional tomographic images for the detection of morphological
      temporomandibular joint (TMJ) changes. METHODS: 80 dry human skulls were scanned
      using a NewTom 3G scanner and lateral and frontal reconstructions of the right
      and the left TMJs were performed. In addition, lateral and frontal cross
      sectional tomograms of the skulls' TMJs were obtained in a Cranex Tome unit with
      Digora storage phosphor plates. Naked-eye inspection of the TMJs performed by
      three observers served as the gold standard for the true presence of
      morphological changes. The mandibular fossae were excluded from the study due to
      few changes in this joint component. The NewTom and the conventional tomographic
      images were examined by three independent observers using a binary scale for the
      presence of morphological changes in the condyle (flattening, defects and
      osteophytes) and the articular tubercle (flattening and defects). The accuracy
      for the different types of changes in relation to the condyles and the articular
      tubercles was expressed as sensitivity and specificity values, whereas the
      diagnostic accuracy for a general assessment including all changes in both joint
      components was expressed by the sum of cases where the gold standard and the
      radiographic scores were not identical (absolute difference). Differences between
      the two radiographic modalities were tested by paired t-test. RESULTS: Detection
      of the various types of morphological changes in relation to the condyle and the
      articular tubercle assessed separately resulted in no significant differences
      between the two radiographic modalities, with the exception of bone defects in
      the articular tubercle examined on frontal views alone where the specificity with
      tomography was significantly higher than with cone beam CT. Detection of all
      morphological changes in relation to both the condyle and the articular tubercle
      showed a significantly higher accuracy with tomography than with cone beam CT
      using lateral views alone, but there was no significant difference between the
      two modalities using frontal views alone and lateral and frontal views in
      combination. CONCLUSION: In general, no significant differences in diagnostic
      accuracy for the detection of bone changes in the condyle and in the articular
      tubercle were found between cone beam CT images and conventional tomograms.

PMID- 17536086
TI  - Beam hardening artefacts occur in dental implant scans with the NewTom cone beam
      CT but not with the dental 4-row multidetector CT.
AB  - OBJECTIVES: The aim of this study was to examine beam hardening artefacts of the
      NewTom 9000 cone-beam computed tomography (CBCT) device compared with the Philips
      MX 8000 (4-row multidetector CT (MDCT)). METHODS: We modified a SawBone skull to
      become a standardized model for our study. The skull was used for scans with the
      NewTom 9000 CBCT device and a standard dental multi-detector CT (MDCT) at a
      comparable reconstruction resolution with a standard Straumann ITI 4.1 mm implant
      in four implant positions in the maxilla (first permanent premolar in the right
      maxilla region, second permanent molar in the right maxilla region, first
      permanent premolar in the left maxilla region and second permanent molar in the
      left maxilla region). Results were compared with construction data of the dental
      implant. An image quality assessment of the images from both devices was
      performed with four experienced physicians and statistically analysed with the
      two-tailed Wilcoxon test. RESULTS: Scans with the NewTom 9000 CBCT showed strong
      beam hardening artefacts in the form of a radiation beam shadow in all
      reconstructions compared with the MDCT. These imaging artefacts became stronger
      with greater distance from the centre of the scanned volume. These differences in
      the imaging quality were proved as significant in a quality evaluation by four
      experienced physicians (P<0.05). CONCLUSIONS: Visual spatial resolution of the
      NewTom 9000 CBCT was less accurate than the Philips MX 8000 MDCT in the imaging
      of metallic dental implants.

PMID- 17536087
TI  - Detection of proximal caries with high-resolution and standard resolution digital
      radiographic systems.
AB  - AIMS: The aim of this study was to: (1) compare the diagnostic accuracy of the
      high-resolution and standard resolution settings of four digital imaging systems
      for caries diagnosis and (2) compare the effect on the diagnostic accuracy of
      reducing the high-resolution image sizes to the standard resolution dimensions,
      and vice versa. MATERIALS AND METHODS: 90 extracted human premolars were mounted
      in groups of 5 in plaster blocks, containing 4 test teeth and 1 non-test tooth.
      Two blocks at a time were placed in a jig to simulate a bitewing radiograph.
      Radiographs were taken using four digital systems (Planmeca Dixi 2; Gendex
      Visualix HDI; Durr Vistascan; Digora Optime), each at two resolution settings.
      Next, the teeth were sectioned and a total of 65 surfaces were incorporated in
      the study. Additionally, the bicubic interpolation method was applied to reduce
      the high-resolution original images and to enlarge the standard resolution
      images. The original, reduced and enlarged images were randomly shown to five
      observers in two random sessions. The observers were asked to assess caries depth
      on a 4-point scale. The observers' scores were compared with the results from a
      histological examination. Data were analysed using the statistical theory for
      multivariate discrete data. Cohen's kappa was used to determine the agreement
      with the gold standard. RESULTS: None of the comparisons between the spatial
      resolution settings, or the comparisons between increased or reduced image size
      and the original image sizes, showed significant differences in the probability
      of caries detection (chi2=26.59, df=26, P approximately 0.50). The four digital
      systems used in this study differ significantly in the probability of caries
      detection (chi2=41.55, df=24, P<0.02). Compared with the gold standard, the
      Gendex Visualix HDI CCD sensor has the highest measure of agreement (kappa=0.31).
      CONCLUSION: Caries diagnosis does not improve when using high-resolution settings
      compared with the standard settings. The use of bicubic convolution interpolation
      for zooming has no detectable effect on caries diagnosis and therefore is
      recommended to use when enlarging or reducing radiographs. The probability of
      caries detection, however, was different for the sensor systems of the different
      manufacturers.

PMID- 17536088
TI  - Morphometric analysis of experimentally induced periapical lesions: radiographic
      vs histopathological findings.
AB  - OBJECTIVES: To evaluate the accuracy and reliability of conventional (Kodak
      Ektaspeed Plus film) and digitized radiographic images to detect the presence as
      well to estimate the size, as measured by an image analysis programme, of
      periapical radiolucencies induced in dog teeth in comparison with the
      histomorphometric data obtained from the same lesions by conventional and
      fluorescence microscopy. METHOD: After the removal of pulp, the root canals of
      five premolars from the same animal were left exposed for 7 days after which they
      were sealed for 60 days. At day 53, three more premolars were opened and left
      exposed to the oral cavity for 7 days. Intact premolars were used as control.
      Conventional radiographs were taken at day 0, day 7, day 30, day 45 and day 60.
      Morphometry in digitized radiographic images and histological sections were
      compared at day 7 and day 60 after setting the experimental series. RESULTS:
      Radiographically, periapical lesions were only detected 30 days after coronal
      sealing. A progressively increasing radiolucent lesion area was observed at day
      45 and day 60. Histopathologically, 7 days after pulp removal dense inflammatory
      infiltrate and root resorption in the periapical region was observed. At day 7
      and day 60, the lesion sizes were similar when evaluated by both conventional and
      fluorescence microscopy. Lesion size was about 20% larger in digitized
      radiographs in comparison with histological measurements. CONCLUSIONS: Although
      image digitization could not improve the detection of the early stages of
      periapical lesions, it provides a valuable quantitative assessment of extensive
      periapical lesions. In addition, fluorescence light microscopy enhances the
      visualization of the apical and periapical structures and seems to be a highly
      useful tool for histological evaluation, valuable for both qualitative and
      quantitative studies of periapical disease.

PMID- 17536089
TI  - Functional evaluations of the parotid and submandibular glands using dynamic
      magnetic resonance sialography.
AB  - PURPOSE: To evaluate the functional differences between the parotid and
      submandibular glands using dynamic MR sialography. METHODS: In 30 volunteers, the
      time-dependent changes (dynamic changes) in the maximum area of the detectable
      parotid and submandibular gland ducts on dynamic MR sialographic images were
      analysed. RESULTS: Dynamic changes in the parotid gland ducts were detectable on
      MR sialographic images in all volunteers, but images of the submandibular gland
      ducts were detectable in only 23 volunteers. In addition, the dynamic changes in
      the submandibular gland ducts in these 23 subjects were less than those seen in
      the parotid gland ducts. A relationship was found between the changing ratio of
      parotid (Pearson r=0.448, P=0.013) or submandibular gland ducts (Pearson r=0.418,
      P=0.047) and the salivary flow rate during the stimulation period. CONCLUSIONS:
      Dynamic MR sialography allows evaluation of rest and stimulated functioning and
      morphological evaluation of the parotid and submandibular glands. This technique
      appears to have many possible applications in the dental, medical and biological
      fields.

PMID- 17536090
TI  - Comparison of re-exposure rates of intraoral radiographs between dental students
      and trained dental assistants in an oral and maxillofacial radiology clinic.
AB  - OBJECTIVE: To compare the re-exposure rates of dental radiographs taken over a
      period of 1 year between dental students and trained dental assistants at a
      university-based oral and maxillofacial radiology clinic. METHODS: Detailed
      records of the number and type of intraoral radiographs taken by the students and
      staff members and the number of re-exposures that were required from July 2003 to
      July 2004 were used. Statistical analyses were performed on the data. RESULTS: A
      chi2 test showed that re-exposure rates of radiographic series between students
      and staff were statistically different. When comparing the students' re-exposure
      rates during each of the four quarters of their radiology rotation, one-way
      analysis of variance test showed that the results were not statistically
      significant for reduction in the number of re-exposures over the entire year.
      CONCLUSIONS: There were significant differences in the re-exposure rates between
      staff dental assistants and students. Film re-exposure rates for the students
      during the four quarters were expected to decrease with time. Instead, the
      consistency of the re-exposure rates of the students during the four quarters
      demonstrates the need to recognize why the students did not perform better as the
      year progressed. The percentage of films that needed to be re-exposed by either
      group (students or the staff dental assistants) was not extremely high.

PMID- 17536091
TI  - Transtomography for implant placement guidance in non-invasive surgical
      procedures.
AB  - OBJECTIVES: To illustrate the use of transtomography for the placement of
      implants using a radiopaque radiographic guide and to evaluate the accuracy of
      transtomography. METHODS: The study included 11 implants inserted with minimally
      invasive procedures. Pre-operative, intraoperative and post-operative
      examinations were performed with a ProMax panoramic unit implemented with
      transtomographic technique (Planmeca Oy, Helsinki, Finland). At each implant
      site, cross-sectional and longitudinal intraoperative transtomograms were taken
      through a radiopaque reference guide to control and adjust the drilling axis. The
      effective axis on post-operative transtomograms was compared with the planned
      axis correction estimated on intraoperative images. Radiopaque guides, used as
      the gold standard, were measured on intraoperative cross-sectional slices to
      evaluate image distortion. RESULTS: Intraoperative transtomograms, with the
      reference guide inserted in the bone, gave clear images of the cortical plates
      and accurate information of drilling length and axis, which allowed the surgeon
      to adjust pilot drilling axis in 6 sites (54.5%) out of 11 sites, including sites
      with narrow bone ridges. The implant axis on the post-operative tomogram compared
      with the planned axis correction showed an angle difference ranging from 0.8
      degrees to 3.4 degrees. The image distortion on cross-sectional slices ranged
      from 0.03 mm to 0.52 mm, resulting in a distortion ratio ranging from 0% to 6%
      when expressed in percentages. CONCLUSIONS: Transtomographic examination
      performed with a radiographic reference guide during implant surgery can provide
      the necessary and accurate information for implant placement. Transtomography
      distortion appears to be less important than in other conventional tomographic
      systems and comparable with CT scan distortion.

PMID- 17536092
TI  - Computed tomography enhancement characteristics of lymphomatous lymph nodes of
      the neck.
AB  - OBJECTIVES: The objective of this study was to investigate prospectively CT
      contrast medium enhancement curves of lymphomatous lymph nodes of the neck.
      MATERIALS AND METHODS: Eleven patients with biopsy-proven lymphoma had their
      enlarged cervical lymph nodes examined with dynamic CT and compared with a
      control group. RESULTS: The mean contrast medium enhancement of the lymphomatous
      nodes was significantly lower than that of the control group in the time interval
      from 40 s to 180 s after injection. DISCUSSION: The enhancement pattern
      previously suggested from studies of retroperitoneal lymph nodes was confirmed in
      this prospective study of cervical nodes.

PMID- 17536093
TI  - Dacryolith: two case reports.
AB  - Dacryolith is a concretion within the nasolacrimal system. Dacryoliths may cause
      intermittent epiphora without inflammation, or recurrent dacryocystitis may
      develop. In this report, we present two patients with dacryoliths. The first
      patient had presented with a complaint of swelling and epiphora and had been told
      that she had lacrimal canal obstruction. This patient was unaware of the cause of
      obliteration and was asymptomatic. The second patient complained of headache, eye
      swelling and inflammation; dacryolith was diagnosed by clinical examination and
      dacryocystography. Dacryoliths were detected on the panoramic radiographs as
      small, rounded, radiopaque calcifications located in the inner aspect of the
      medial wall of the orbit. The image of dacryoliths must be differentiated from
      radiographic artefacts and foreign objects, and it is important to recognize
      dacryoliths on panoramic radiographs and to refer the patients for medical care,
      if necessary.

PMID- 17536094
TI  - Intraorbital plexiform neurofibroma in an NF-1-negative patient.
AB  - A 52-year-old patient presented with an orbital swelling and exophthalmos that
      enlarged over a period of about 40 years. The clinical examination showed massive
      exophthalmos and ptosis of the right eye without diplopia. The radiological
      investigation (MRI, CT and ultrasound) showed an unclear intraorbital mass with
      erosion of the orbital floor, infraorbital rim and orbital roof. The lesion was
      diagnosed histologically as a plexiform neurofibroma. The patient did not present
      any features of neurofibromatosis type 1 (NF-1) and molecular genetic analysis
      was unable to uncover a pathogenic sequence alteration in the NF-1 gene. Owing to
      the absence of clinical and ophthalmologic symptoms and the improbability of
      complete removal, the patient refused surgical intervention.

PMID- 17536095
TI  - A case of neglected inverted papilloma with invasion to the skin.
AB  - Inverted papilloma is an uncommon and locally aggressive benign tumour of the
      sinonasal region, which tends to recur after surgical resection and is
      occasionally associated with squamous cell carcinoma. The following report
      describes the initial history, physical examination, radiological studies,
      operative and histopathologic reports and differential diagnosis of a case of
      inverted papilloma with wide extension into the adjacent structures and unique
      clinical appearance.

PMID- 17536097
TI  - The impact of X-ray crystallography and NMR on intracellular calcium signal
      transduction by EF-hand proteins: crossing the threshold from structure to
      biology and medicine.
AB  - The use of x-ray crystallography and solution nuclear magnetic resonance (NMR)
      spectroscopy has revolutionized our understanding of the transduction of
      intracellular calcium signals into cellular responses. Indeed, the ability to
      cross a critical threshold from basic descriptive structural biochemistry to real
      world applications in therapeutics and biotechnology now looms on the
      experimental horizon. The ~500 atomic resolution structures determined by x-ray
      and NMR approaches and deposited in the Protein Data Bank, many of which are of
      complexes of EF-hand proteins with peptide fragments of cellular targets, have
      yielded an extremely thorough description for how EF-hand proteins respond to the
      binding of calcium. Although this database of structures is a powerful structural
      tool to describe EF-hand protein function, it is limited in its ability to have a
      significant impact on biology and medicine because the structural effects on the
      downstream target are not determined. The opportunity that now lies before us is
      to extend this EF-hand-centric structural information so that the alterations in
      the target proteins are defined and the structural basis for functional
      consequences downstream is understood.

PMID- 17536098
TI  - Parsing the motion of single molecules: a novel algorithm for deconvoluting the
      dynamics of individual receptors at the cell surface.
AB  - To truly understand signal transduction, we will ultimately need to understand
      the dynamics and kinetics of individual proteins as they perform their functions
      in a single cell. Groundbreaking advances in single-molecule biophysics now allow
      us to follow the motion of many individual proteins on the cell surface with the
      use of fluorescent probes, such as quantum dots. However, discriminating the
      directed movement of single molecules from their natural Brownian motion remains
      a challenge. A recent paper provides a powerful statistical approach for
      distinguishing periods of directed motion of individual gamma-aminobutyric acid
      (GABA) receptors from periods during which they undergo Brownian motion. This new
      methodology should help single-molecule researchers determine the dynamics of
      individual proteins participating in signaling cascades.

PMID- 17536099
TI  - Microfluidic devices for the analysis of single cells: leaving no protein
      uncounted.
AB  - Microfluidic devices are revolutionizing bioanalysis, and designs capable of
      detecting single protein molecules are now available. Two recently described
      microfluidic devices provide information on the number of beta(2)-adrenergic
      receptors in individual cultured insect cells and measure the degradation of
      phycobilisomes in individual cyanobacteria, respectively. This latter experiment,
      which included the analysis of three single cells in parallel, heralds a bright
      future for high-throughput single-cell analyzers. These devices could greatly
      advance research in signal transduction and studies of the effects of
      environmental stimuli or xenobiotics on cellular responses.

PMID- 17536100
TI  - NRC final rule on expanded definition of byproduct material.

PMID- 17536102
TI  - A definition of molecular imaging.

PMID- 17536104
TI  - State of the profession.

PMID- 17536105
TI  - Beyond detection: novel applications for PET imaging to guide cancer therapy.

PMID- 17536106
TI  - Total thyroidectomy and adjuvant radioiodine treatment independently decrease
      locoregional recurrence risk in childhood and adolescent differentiated thyroid
      cancer.
AB  - We sought to assess whether extensive surgical treatment, postsurgical
      radioiodine therapy, or both decrease the risk of locoregional recurrence (LR)
      after curative primary treatment in children and adolescents diagnosed with
      differentiated thyroid cancer (DTC) at age <or=18 y. METHODS: To determine the
      incidence of and identify predictive factors for thyroid bed recurrence (TBR) or
      lymph node recurrence (NR), we performed a chart review and retrospective
      multivariate Cox regression analysis on 235 patients with DTC diagnosed at age
      <or=18 y and managed with curative intent at our tertiary referral center from
      1973 to 2002; 40 of these patients had distant metastases at diagnosis. We also
      determined overall and recurrence-free survival and generated curves for these
      variables using Kaplan-Meier and Cox univariate analysis. RESULTS: During a
      median follow-up of 82 mo (range, 5-402 mo), no DTC-related deaths occurred, 203
      (86%) children remained recurrence-free, and 32 (14%) children had LR, including
      TBR in 9 (28% of LR), NR in 20 (63% of LR), and both in 3 (9% of LR). Among
      patients treated with radical intent and showing no distant metastases, the most
      recent thyroglobulin level was <1 ng/mL in all but 4% of cases. The median time
      from the first surgery to LR was 37 mo (range, 9-280 mo). In multivariate
      analysis, significant risk factors for TBR were less than total thyroidectomy and
      lack of postsurgical radioiodine treatment (respective risk increases of 9.5 [P =
      0.04] and 11 times [P = 0.03]). For NR, classic papillary histology, incomplete
      primary lymph node management (i.e., lack of modified lymphadenectomy of affected
      lymph nodes or lack of confirmation of disease-free nodes by intraoperative
      staging), and absence of adjuvant radioiodine therapy were independent
      significant predictive factors that increased the recurrence risk by 1.9 (P =
      0.02), 3.3 (P = 0.02), and 3.2 (P = 0.02) times, respectively. Age or sex did not
      correlate with LR risk. CONCLUSION: In DTC patients <or=18 y of age, extensive
      initial therapy-consisting of total thyroidectomy combined with modified
      lymphadenectomy performed in case of lymph node metastases and followed by
      radioiodine therapy--is associated with a substantial decrease of DTC LR risk.

PMID- 17536107
TI  - PET measurements of myocardial glucose metabolism with 1-11C-glucose and kinetic
      modeling.
AB  - The aim of this study was to investigate whether compartmental modeling of 1
      (11)C-glucose PET kinetics can be used for noninvasive measurements of myocardial
      glucose metabolism beyond its initial extraction. METHODS: 1-(11)C-Glucose and U
      (13)C-glucose were injected simultaneously into 22 mongrel dogs under a wide
      range of metabolic states; this was followed by 1 h of PET data acquisition.
      Heart tissue samples were analyzed for (13)C-glycogen content (nmol/g). Arterial
      and coronary sinus blood samples (ART/CS) were analyzed for glucose (mumol/mL),
      (11)C-glucose, (11)CO(2), and (11)C-total acidic metabolites ((11)C-lactate [LA]
      + (11)CO(2)) (counts/min/mL) and were used to calculate myocardial fractions of
      (a) glucose and 1-(11)C-glucose extractions, EF(GLU) and EF((11)C-GLU); (b) (11)C
      GLU and (11)C-LA oxidation, OF((11)C-GLU) and OF((11)C-LA); (c) (11)C
      glycolsysis, GCF((11)C-GLU); and (d) (11)C-glycogen content, GNF((11)C-GLU). On
      the basis of these measurements, a compartmental model (M) that accounts for the
      contribution of exogenous (11)C-LA to myocardial (11)C activity was implemented
      to measure M-EF(GLU), M-GCF(GLU), M-OF(GLU), M-GNF(GLU), and the fraction of
      myocardial glucose stored as glycogen M-GNF(GLU)/M-EF(GLU)). RESULTS: ART/CS data
      showed the following: (a) A strong correlation was found between EF((11)C-GLU)
      and EF(GLU) (r = 0.92, P < 0.0001; slope = 0.95, P = not significantly different
      from 1). (b) In interventions with high glucose extraction and oxidation, the
      contribution of OF((11)C-GLU) to total oxidation was higher than that of OF((11)C
      LA) (P < 0.01). In contrast, in interventions in which glucose uptake and
      oxidation were inhibited, OF((11)C-LA) was higher than OF((11)C-GLU) (P < 0.05).
      (c) A strong correlation was found between GNF((11)C-GLU)/EF(GLU) and direct
      measurements of fractional (13)C-glycogen content, (r = 0.96, P < 0.0001). Model
      derived PET measurements of M-EF(GLU), M-GCF(GLU), and M-OF(GLU) strongly
      correlated with EF(GLU) (slope = 0.92, r = 0.95, P < 0.0001), GCF((11)C-GLU)
      (slope = 0.79, r = 0.97, P < 0.0001), and OF((11)C-GLU) (slope = 0.70, r = 0.96,
      P < 0.0001), respectively. M-GNF(GLU)/M-EF(GLU) strongly correlated with
      fractional (13)C-content (r = 0.92, P < 0.0001). CONCLUSION: Under nonischemic
      conditions, it is feasible to measure myocardial glucose metabolism noninvasively
      beyond its initial extraction with PET using 1-(11)C-glucose and a compartmental
      modeling approach that takes into account uptake and oxidation of secondarily
      labeled exogenous (11)C-lactate.

PMID- 17536108
TI  - Pretreatment 18F-FAZA PET predicts success of hypoxia-directed radiochemotherapy
      using tirapazamine.
AB  - We evaluated the predictive value of PET using the hypoxia tracer (18)F
      fluoroazomycin arabinoside ((18)F-FAZA) for success of radiotherapy in
      combination with tirapazamine, a specific cytotoxin for hypoxic cells. METHODS:
      Imaging was performed on EMT6 tumor-bearing nude mice before allocating mice into
      4 groups: radiochemotherapy (RCT: 8 fractions of 4.5 Gy within 4 d combined with
      tirapazamine, 14 mg/kg), radiotherapy alone (RT), chemotherapy alone
      (tirapazamine) (CHT), or control. Treatment success was assessed by several tumor
      growth assays, including tumor growth time from 70 to 500 microL and absolute
      growth delay (aGD). The median pretreatment (18)F-FAZA tumor-to-background ratio
      served as a discriminator between "hypoxic" and "normoxic" tumors. RESULTS: The
      mean tumor growth was significantly accelerated in hypoxic control tumors (growth
      time from 70 to 500 microL, 11.0 d) compared with normoxic control tumors (growth
      time from 70 to 500 microL, 15.6 d). Whereas RT delayed tumor growth regardless
      of the level of hypoxia, an additive beneficial therapeutic effect of
      tirapazamine to RT was observed only in hypoxic tumors (aGD, 12.9 d) but not in
      normoxic tumors (aGD, 6.0 d). CONCLUSION: This study provides compelling evidence
      that hypoxia imaging using (18)F-FAZA PET is able to predict the success of RCT
      of tumor-bearing mice using the hypoxia-activated chemotherapeutic agent
      tirapazamine. Pretreatment (18)F-FAZA PET, therefore, offers a way for the
      individualization of tumor treatment involving radiation. The data suggest that
      by reserving hypoxia-directed therapy to tumors with high (18)F-FAZA uptake,
      improvement of the therapeutic ratio is possible, as the therapeutic effect of
      tirapazamine seems to be restricted to hypoxic tumors.

PMID- 17536109
TI  - Imaging acute cardiac cell death: temporal and spatial distribution of 99mTc
      labeled C2A in the area at risk after myocardial ischemia and reperfusion.
AB  - The exposure of anionic phospholipids is a near-universal molecular signature for
      cell death. Based on our prior finding that the (99m)Tc-labeled C2A domain of
      synaptotagmin I accumulates intensely in the area at risk, this study
      quantitatively characterized the temporal and spatial distribution of the
      radiotracer in a rat model of myocardial ischemia and reperfusion. METHODS:
      Myocardial ischemia and reperfusion were induced by occlusion of the left
      anterior descending coronary artery in rats. The temporal uptake of the labeled
      fusion protein of C2A and glutathione-s-transferase (C2A-GST) in the area at risk
      was investigated by intravenously injecting the radiotracer at 0, 1, 3, 6, and 24
      h after reperfusion, and the radioactivity uptake was quantified by gamma
      counting of infarcted and ischemic noninfarcted cardiac tissues. Alternatively,
      the radiotracer was injected at 2 h after reperfusion, and the uptake was
      measured at 1, 3, 6, and 24 h after injection. In vivo planar imaging was
      performed on a gamma-camera using a parallel-hole collimator. The distribution of
      radioactivity was qualitatively examined by autoradiography. The relationship
      between the uptake of the radiotracer in the area at risk and the ischemic
      duration was examined by gamma-counting. RESULTS: Temporally, the radioactivity
      uptake in the area at risk maximized when the radiotracer was injected before 3 h
      after reperfusion. Injections at 6 and 24 h after reperfusion resulted in a 30%
      and 50% reduction in uptake, respectively. However, when the injection was done
      early (2 h after reperfusion), the tracer was retained in the area at risk with
      little washout for at least 24 h. Spatially prominent hot-spot uptake was seen in
      all cases of planar imaging. In autoradiography, the distribution of
      radioactivity predominantly coregistered with the infarcted regions. This
      distribution profile was confirmed by direct gamma-counting. In addition, the
      absolute radiotracer uptake in the infarcted and ischemic noninfarcted tissues,
      in terms of percentage injected dose per gram, was independent of the ischemic
      duration. CONCLUSION: (99m)Tc-C2A-GST has an uptake profile in the area at risk
      that is appropriate for imaging cardiac cell death in the acute phase.

PMID- 17536110
TI  - Comparison of 64-slice CT with gated SPECT for evaluation of left ventricular
      function.

PMID- 17536113
TI  - Pulmonary arterial hypertension: an overview.
AB  - Pulmonary arterial hypertension (PAH) was first described over 100 years ago, but
      a thorough understanding of its patho-genesis and a successful approach to curing
      the disease remain elusive. Increased research activity has greatly enhanced our
      understanding of the disease and led to new therapies that retard disease
      progression and improve patient function and survival. The disease is rare, but
      effects people of all ages and is associated with several seemingly unconnected
      diseases. It is not clear whether all forms of PAH represent the same disease or
      the same pathologic endpoint of different pulmonary vascular disease processes.
      Recent attempts to classify different forms of pulmonary hyper-tension by the
      diseases with which they are associated has helped researchers organize data
      collected from patient registries and clinical trials. This overview discusses
      the history, epidemiology, and genetic basis of PAH, new recommendations for
      disease classification, and prognostic variables shown to adversely affect
      survival.

PMID- 17536114
TI  - Pathophysiology of pulmonary arterial hypertension.
AB  - The mechanisms leading to elevations in precapillary pulmonary vascular
      resistance are complex and likely involve multiple pathways, but the
      histopathologic sequelae of these processes are restricted to a few findings,
      primarily neoangiogenesis, intimal and smooth muscle proliferation,
      vasoconstriction, and/or in situ thrombosis. Regardless of the etiology of
      pulmonary hypertension, abnormalities in endothelial function are often observed
      and likely play a central role in mediating structural changes.

PMID- 17536115
TI  - Clinical presentation, differential diagnosis, and vasodilator testing of
      pulmonary hypertension.
AB  - Clinicians should be cognizant of the symptoms and risk factors associated with
      pulmonary hypertension (PH). While known PH poses significant therapeutic
      challenges, occult PH carries the added potential for unanticipated complications
      when treating concurrent medical illnesses. PH may occur with underlying medical
      conditions and risk factors or may occur de novo as idiopathic pulmonary arterial
      hypertension (IPAH). Symptoms of PH are frequently attributed to more common
      conditions, and their nonspecific nature and insidious onset may lead to delay in
      presentation, evaluation, and diagnosis. Initial symptoms are dyspnea, fatigue,
      chest pain, and palpitations. Lower extremity edema, presyncope, and syncope are
      symptoms of more advanced disease. Thorough evaluation of symptoms and
      identification of patients with risk factors for PH are critical in making a
      timely diagnosis. History and physical examination can identify patients with
      suspected PH. Further testing is necessary for definitive diagnosis,
      classification, assessment of severity, and guiding therapeutic decisions.

PMID- 17536116
TI  - Management of pulmonary hypertension in the operating room.
AB  - Pulmonary artery hypertension is defined as persistent elevation of mean
      pulmonary artery pressure > 25 mm Hg with pulmonary capillary wedge pressure < 15
      mm Hg or elevation of exercise mean pulmonary artery pressure > 35 mm Hg.
      Although mild pulmonary hypertension rarely impacts anesthetic management, severe
      pulmonary hypertension and exacerbation of moderate hypertension can lead to
      acute right ventricular failure and cardiogenic shock. Knowledge of anesthetic
      drug effects on the pulmonary circulation is essential for anesthesiologists.
      Intraoperative management should include prevention of exacerbating factors such
      as hypoxemia, hypercarbia, acidosis, hypothermia, hypervolemia, and increased
      intrathoracic pressure; monitoring and optimizing right ventricular function; and
      treatment with selective pulmonary vasodilators. Recent advances in pharmacology
      provide anesthesiologists with a wide variety of options for selective pulmonary
      vasodilatation. Pulmonary hypertension is a major determinant of perioperative
      morbidity and mortality in special situations such as heart and lung
      transplantation, pneumonectomy, and ventricular assist device placement.

PMID- 17536117
TI  - Current therapies for pulmonary arterial hypertension.
AB  - Pulmonary arterial hypertension (PAH) is a progressive disease of the pulmonary
      vasculature, characterized by relentless deterioration and death. Patients with
      PAH are known to be at increased risk for anesthetic complications and surgical
      morbidity and mortality. However, outcomes in patients have improved with the
      recent development of new drug therapies. The 3 major drug classes for treatment
      of PAH are prostanoids, endothelin-receptor antagonists, and phosphodiesterase-5
      inhibitors. In this review, the authors provide an overview of each drug class,
      its mechanism of action, indications, and current supportive literature. Surgical
      and interventional treatments of PAH, including atrial septostomy, pulmonary
      thromboendarterectomy, and transplantation, are briefly reviewed, and the
      rationale, indications, and selection criteria for each are discussed. Although
      available medical and surgical therapies for PAH have improved patient outcomes,
      acute decompensated right heart failure (RHF) remains a common and challenging
      complication of PAH. The authors review this topic and provide an outline of the
      general pathophysiology of RHF and an approach to its management.

PMID- 17536118
TI  - Lung transplantation and pulmonary hypertension.
AB  - The presence of pulmonary hypertension affects lung transplantation in multiple
      ways, from patient selection, transplant risks, type of transplant,
      intraoperative management, to transplant outcome. A working knowledge of natural
      disease progression, the latest medical treatment options, and transplant outcome
      is critical in patient selection, and a good understanding of the transplant
      process, including the new transplant allocation system, is important for
      physicians involved in the care of patients with pulmonary arterial hypertension.
      The complexity of these factors underscores the importance of good communication
      between referring physicians and transplant centers.

PMID- 17536119
TI  - Dietary management of type 2 diabetes: a personal odyssey.

PMID- 17536120
TI  - Acute EGCG supplementation reverses endothelial dysfunction in patients with
      coronary artery disease.
AB  - BACKGROUND: Epidemiological studies demonstrate an inverse relation between
      dietary flavonoid intake and cardiovascular risk. Recent studies with flavonoid
      containing beverages suggest that the benefits of these nutrients may relate, in
      part, to improved endothelial function. OBJECTIVE: We hypothesized that dietary
      supplementation with epigallocatechin gallate (EGCG), a major catechin in tea,
      would improve endothelial function in humans. DESIGN: We examined the effects of
      EGCG on endothelial function in a double blind, placebo-controlled, crossover
      design study. We measured brachial artery flow-mediated dilation by vascular
      ultrasound at six time points: prior to treatment with EGCG or placebo, two hours
      after an initial dose of EGCG (300 mg) or placebo, and after two weeks of
      treatment with EGCG (150 mg twice daily) or placebo. The order of treatments
      (EGCG or placebo) was randomized and there was a one-week washout period between
      treatments. RESULTS: A total of 42 subjects completed the study, and brachial
      artery flow-mediated dilation improved from 7.1 +/- 4.1 to 8.6 +/- 4.7% two hours
      after the first dose of 300 mg of EGCG (P = 0.01), but was similar to baseline
      (7.8 +/- 4.2%, P = 0.12) after two weeks of treatment with the final measurements
      made approximately 14 hours after the last dose. Placebo treatment had no
      significant effect, and there were no changes in reactive hyperemia or the
      response to sublingual nitroglycerin. The changes in vascular function paralleled
      plasma EGCG concentrations, which increased from 2.6 +/- 10.9 to 92.8 +/- 78.7
      ng/ml after acute EGCG (P < 0.001), but were unchanged from baseline after two
      weeks of treatment (3.4 +/- 13.1 ng/ml). CONCLUSION: EGCG acutely improves
      endothelial function in humans with coronary artery disease, and may account for
      a portion of the beneficial effects of flavonoid-rich food on endothelial
      function.

PMID- 17536121
TI  - Renal and gastrointestinal potassium excretion in humans: new insight based on
      new data and review and analysis of published studies.
AB  - OBJECTIVES: Little is known about the relationship between the renal and
      gastrointestinal excretion of potassium in humans. This information is important
      in light of strong associations of potassium intake with hypertension and
      occlusive stroke. METHODS: We determined the relationship between fecal and
      urinary excretion of potassium under both fixed and variable potassium intakes
      using our unpublished archival data and published data of others. Twenty-five
      subjects were evaluated. RESULTS: On a fixed, low oral potassium intake (61.2 +/-
      4.7 mmol/day; mean +/- SD), there was an inverse relationship between fecal and
      urinary potassium excretion (r = -0.66, p = 0.040). In studies in which potassium
      intake varied between 61-135 mmol/day, fecal and urinary potassium excretions
      were positively correlated (r = 0.58, p = 0.024). Considerable within-and-between
      subject variation was observed in the relationship between fecal and urinary
      potassium excretion. CONCLUSIONS: Inter-individual variation in fecal potassium
      excretion may arise from both variation in dietary potassium intake and intrinsic
      individual differences in the renal versus gastrointestinal handling of
      potassium.

PMID- 17536122
TI  - Multivitamin-mineral supplementation prevents lipid peroxidation during "the
      Marathon des Sables".
AB  - OBJECTIVE: We investigated the effect of a moderate mutivitamin and mineral
      supplementation containing mainly vitamin C (150.0 mg.day(-1)), vitamin E (24.0
      mg.day(-1)) and beta-carotene (4.8 mg.day(-1)) prior to and during an extreme
      running competition -the Marathon des Sables (MDS)- that consisted of six long
      races in the desert. METHODS: Seventeen athletes participated in our double
      blind, placebo-controlled study. Blood samples were collected prior to the
      supplementation i.e. three weeks before the competition (D-21), two days prior to
      the MDS (D-2), after the third race (D3) and at the end of the competition (D7).
      Erythrocyte antioxidant enzyme activity (glutathione peroxidase (GPx), superoxide
      dismutase (SOD)), erythrocyte glutathione level (GSH), plasma non-enzymatic
      antioxidant status (uric acid, vitamin C, alpha-tocopherol, retinol, beta
      carotene), markers of plasma lipid peroxidation (thiobarbituric reactive
      substances (TBARS)), reactive carbonyl derivatives (RCD) and membrane damage
      (creatine kinase and lactate dehydrogenase activities) were measured. RESULTS: In
      both groups, GSH levels, uric acid levels and membrane damage significantly
      increased during the competition while SOD activity significantly decreased. In
      Supplemented group, plasma alpha-tocopherol, beta-carotene and retinol levels
      significantly increased after three weeks of supplementing. In contrast to
      Placebo group, alpha-tocopherol, vitamin C and retinol levels were significantly
      affected by the competition in Supplemented group. Moreover, no increase in TBARS
      was observed in Supplemented group during the competition, whereas TBARS
      significantly increased at D3 in the placebo group. CONCLUSION: The moderate
      multivitamin-mineral supplementation prevented the transient increase in TBARS
      levels during this extreme competition.

PMID- 17536123
TI  - Dietary magnesium deficiency induces heart rhythm changes, impairs glucose
      tolerance, and decreases serum cholesterol in post menopausal women.
AB  - OBJECTIVE: To determine whether or not dietary magnesium restriction to about 33%
      of the Recommended Dietary Allowance (RDA) causes changes in glucose, cholesterol
      and electrolyte metabolism that could lead to pathologic consequences. DESIGN:
      The length of the experiment was 136 days. Subjects were fed a basal Western-type
      diet that provided 4.16 mmol (101 mg) magnesium per 8.4 MJ (2000 kcal) for 78
      days then replenished with magnesium by supplementing the diet with 200 mg
      magnesium as the gluconate per day for 58 days. If a subject exhibited adverse
      heart rhythm changes before 78 days of depletion were completed, she entered the
      repletion period early. SETTING: The metabolic research unit of the Grand Forks
      Human Nutrition Research Center. SUBJECTS: A total of 14 post menopausal women
      were recruited by advertisement throughout the United States. Thirteen women
      (ages 47 to 75 years) completed the study. RESULTS: During magnesium depletion,
      heart rhythm changes appeared in 5 women and resulted in 4 prematurely entering
      the magnesium repletion period (42 to 64 days of depletion instead of 78). Three
      women exhibited atrial fibrillation and flutter that responded quickly to
      magnesium supplementation. Magnesium deprivation resulted in a non-positive
      magnesium balance that became highly positive with magnesium repletion. Magnesium
      deprivation decreased red blood cell membrane magnesium, serum total cholesterol
      and erythrocyte superoxide dismutase concentrations, increased the urinary
      excretion of sodium and potassium, and increased serum glucose concentration.
      CONCLUSIONS: Magnesium balance may be a suitable indicator of magnesium depletion
      under experimental conditions. Magnesium deficiency resulting from feeding a diet
      that would not be considered having an atypical menu induces heart arrhythmias,
      impairs glucose homeostasis, and alters cholesterol and oxidative metabolism in
      post menopausal women. A dietary intake of about 4.12 mmol (100 mg) Mg/8.4 MJ is
      inadequate for healthy adults and may result in compromised cardiovascular health
      and glycemic control in post menopausal women.

PMID- 17536124
TI  - Dietary linolenic acid intake is positively associated with five-year change in
      eye lens nuclear density.
AB  - OBJECTIVE: Dietary fat may affect lens cell membrane composition and function,
      which are related to age-related cataract. The present study was designed to
      examine the associations between dietary fat and the change in nuclear lens
      opacification over five years. METHODS: Women aged 52 to 73 years without
      previously diagnosed cancer, diabetes and cataracts from the Boston,
      Massachusetts area were selected from the Nurses' Health Study cohort. Four
      hundred forty women participated in a baseline (1993-95) and a follow-up (1998
      2000) eye examination. Intakes of total fat and selected fatty acids were
      calculated as the average intake from five food frequency questionnaires that
      were collected between 1980 and baseline. Change in the degree of nuclear density
      (opacification) was characterized by the difference between baseline and follow
      up in pixel density at the central clear zone in the Scheimpflug slit image of
      the lens. RESULTS: Intake of alpha-linolenic acid (ALA) was positively associated
      with change in nuclear density. The geometric mean nuclear density change was 16%
      greater in the highest quartile category of ALA intake than in the lowest
      quartile category (P for trend = 0.05). For women in the high tertile category of
      baseline nuclear lens opacification, the geometric mean change in the highest
      quartile category of ALA acid intake was 70% higher than the change in the lowest
      quartile category (P for trend = 0.01). There were no significant associations
      between other dietary fats and change in nuclear density. CONCLUSION: Higher ALA
      intake was associated with a greater age-related change in lens nuclear density.

PMID- 17536125
TI  - Pistachio nut consumption and serum lipid levels.
AB  - OBJECTIVE: Clinical and epidemiological studies have reported the beneficial
      effects of tree nuts and peanuts on serum lipid levels. We studied the effects of
      consuming 15% of the daily caloric intake in the form of pistachio nuts on the
      lipid profiles of free-living human subjects with primary, moderate
      hypercholesterolemia (serum cholesterol greater than 210 mg/dL). METHODS: design:
      Randomized crossover trial. setting: Outpatient dietary counseling and blood
      analysis. subjects: 15 subjects with moderate hypercholesterolemia. intervention:
      Fours weeks of dietary modification with 15% caloric intake from pistachio nuts.
      MEASURES OF OUTCOME: Endpoints were serum lipid levels of total cholesterol, HDL
      C, LDL-C, VLDL-C, triglycerides and apolipoproteins A-1 and B-100. BMI, blood
      pressure, and nutrient intake (total energy, fat, protein, and fiber) were also
      measured at baseline, during, and after dietary intervention. RESULTS: No
      statistically significant differences were observed for total energy or percent
      of energy from protein, carbohydrate or fat. On the pistachio nut diet, a
      statistically significant decrease was seen for percent energy from saturated fat
      (mean difference, -2.7%; 95% CI, -5.4% to -0.08%; p = 0.04). On the pistachio nut
      diet, statistically significant increases were seen for percent energy from
      polyunsaturated fat (mean difference, 6.5%; 95% CI, 4.2% to 8.9%; p<.0001) and
      fiber intake (mean difference, 15 g; 95% CI, 8.4 g to 22 g; p = 0.0003). On the
      pistachio diet, statistically significant reductions were seen in TC/HDL-C (mean
      difference, -0.38; 95% CI, -0.57 to -0.19; p = 0.001), LDL-C/HDL-C (mean
      difference, -0.40; 95% CI, -0.66 to -0.15; p = 0.004), B-100/A-1 (mean
      difference, -0.11; 95% CI, -0.19 to -0.03; p = 0.009) and a statistically
      significant increase was seen in HDL-C (mean difference, 2.3; 95% CI, 0.48 to
      4.0; p = 0.02). No statistically significant differences were seen for total
      cholesterol, triglycerides, LDL-C, VLDL-C, apolipoprotein A-1 or apolipoprotein B
      100. No changes were observed in BMI or blood pressure. CONCLUSION: A diet
      consisting of 15% of calories as pistachio nuts (about 2-3 ounces per day) over a
      four week period can favorably improve some lipid profiles in subjects with
      moderate hypercholesterolemia and may reduce risk of coronary disease.

PMID- 17536126
TI  - Lactating women restricting milk are low on select nutrients.
AB  - OBJECTIVE: Currently there are no recommendations for vitamin/mineral
      supplementation for lactating women but supplementation may be important,
      particularly for those women who choose to restrict milk intake during lactation.
      The objective of this study was to assess nutrient adequacy for lactating women
      and compare their dietary intake, including supplements, between those who
      restrict milk and those who do not. METHODS: A cohort of 175 healthy exclusively
      breast-feeding women (19-45 yrs) recruited from prenatal classes were divided
      into milk restrictors (RS) defined as milk intake < or = 250 ml/day and non
      restrictors (NRS) (>250 ml/day) and followed for six months postpartum.
      Participants provided repeated 24-hr dietary recalls, detailed use of
      vitamin/mineral supplements and reasons for restricting milk. STATISTICAL
      ANALYSES: Observed intakes were adjusted to remove day-to-day variability.
      Nutrient intakes were estimated for macronutrients and vitamins C, D, thiamin,
      riboflavin, niacin, and minerals, calcium and zinc, with and without
      vitamin/mineral supplements. Chi-square was used to compare the number of RS and
      NRS with intakes less than the Estimated Average Requirement (EAR). RESULTS: Milk
      restriction was practiced by 23% of the sample. Sixty per cent of RS reported
      protein intakes <EAR compared to 38% of NRS (chi(2) = 6.22, p < 0.05). Prior to
      supplementation, mean levels of calcium and vitamin D intakes for RS were below
      the adequate intake level (AI) and lower than NRS estimated intakes (p < 0.05).
      Following supplementation, mean levels of these nutrients reached AI for both
      groups. RS remained lower than NRS. RS had lower energy intakes than NRS (p <
      0.05) but no difference in weight loss at 6 months was noted. A higher proportion
      of RS were below the EAR for thiamin, riboflavin and zinc. CONCLUSIONS: Milk
      restriction compromised protein and nutrient intakes in lactating women who
      restricted milk to <250 mL. Vitamin/mineral supplements helped exclusively
      breastfeeding milk restrictors improve their vitamin D and calcium intakes. Milk
      restriction is not recommended during lactation and where unavoidable, nutrients
      provided by milk should be compensated for by other foods or supplements.

PMID- 17536127
TI  - Food components and dietary patterns of two different groups of Mexican lactating
      women.
AB  - OBJECTIVE: To evaluate the energy, nutrient intakes and dietary patterns of
      Mexican lactating women at one month postpartum, and the associations of maternal
      age and region on their intakes. METHODS: A total of 60 women were studied: 41
      from Northwest and 19 from Central Mexico, 33 adolescent and 27 adult women. Data
      were collected through two quantitative 24 h recalls. Two more recalls were used
      in a sub sample to calculate the coefficient of variation of intakes. Menus were
      based on the consumption frequency of foods. RESULTS: The mean energy intake of
      the adolescent women (2354 +/- 1199 kcal) and those of Central Mexico (1690 +/-
      981 kcal) was lower than the recommendations. Zinc, calcium, vitamin E, C and
      folate were inadequate (55 to 85% prevalence of inadequacy). Energy, dietary
      fiber, sodium, potassium, iron and folate intakes were higher (P < 0.05) in
      Northwest Mexico. Northwestern women consumed less variety of vegetables or
      fruits compared to Mexico City region women. Wheat tortillas and beans were from
      Northwestern but not from the Mexico City region diet. CONCLUSIONS: The energy
      and nutrient intakes of women were different by regional hospital and not by age.
      Education about the importance of the maternal diet during lactation should be
      directed toward increasing consumption of foods rich in micronutrients.

PMID- 17536128
TI  - Low carbohydrate, high fat diet increases C-reactive protein during weight loss.
AB  - OBJECTIVE: Chronic inflammation is associated with elevated risk of heart disease
      and may be linked to oxidative stress in obesity. Our objective was to evaluate
      the effect of weight loss diet composition (low carbohydrate, high fat, LC or
      high carbohydrate, low fat, HC) on inflammation and to determine whether this was
      related to oxidative stress. METHODS: Twenty nine overweight women, BMI 32.1 +/-
      5.4 kg/m(2), were randomly assigned to a self-selected LC or HC diet for 4 wks.
      Weekly group sessions and diet record collections helped enhance compliance. Body
      weight, markers of inflammation (serum interleukin-6, IL-6; C-reactive protein,
      CRP) oxidative stress (urinary 8-epi-prostaglandin F2alpha, 8-epi) and fasting
      blood glucose and free fatty acids were measured weekly. RESULTS: The diets were
      similar in caloric intake (1357 kcal/d LC vs. 1361 HC, p=0.94), but differed in
      macronutrients (58, 12, 30 and 24, 59, 18 for percent of energy as fat,
      carbohydrate, and protein for LC and HC, respectively). Although LC lost more
      weight (3.8 +/- 1.2 kg LC vs. 2.6 +/- 1.7 HC, p=0.04), CRP increased 25%; this
      factor was reduced 43% in HC (p=0.02). For both groups, glucose decreased with
      weight loss (85.4 vs. 82.1 mg/dl for baseline and wk 4, p<0.01), while IL-6
      increased (1.39 to 1.62 pg/mL, p=0.04). Urinary 8-epi varied differently over
      time between groups (p<0.05) with no consistent pattern. CONCLUSION: Diet
      composition of the weight loss diet influenced a key marker of inflammation in
      that LC increased while HC reduced serum CRP but evidence did not support that
      this was related to oxidative stress.

PMID- 17536129
TI  - Plasma antioxidant capacity changes following a meal as a measure of the ability
      of a food to alter in vivo antioxidant status.
AB  - OBJECTIVE: Determine 1) if consumption of a meal of different fruits or berries
      increases plasma hydrophilic (H-) or lipophilic (L-) antioxidant capacity (AOC)
      measured as Oxygen Radical Absorbance Capacity (ORAC(FL)); 2) if including
      macronutrients in the meal alters postprandial changes in AOC; and 3) if
      preliminary recommendations can be developed for antioxidant intake. METHODS:
      Changes in plasma AOC following consumption of a single meal of berries/fruits
      (blueberry, dried plum, dried plum juice, grape, cherry, kiwifruit and
      strawberry) were studied in 5 clinical trials with 6-10 subjects per experiment.
      In two studies with blueberry or grape, additional macronutrients (carbohydrate,
      fat, protein) were included in the control and treatment meals. Blood samples
      collected before and after the meal were analyzed for AOC. RESULTS: Consumption
      of dried plums or dried plum juice did not alter either the H- or L-AOC area
      under the curve (AUC). Consumption of blueberry in 2 studies and of mixed grape
      powder [12.5 (Study #1), 39.9 (Study #4) and 8.6 (Study #5) mmole Trolox
      Equivalents (TE) AOC, respectively] increased hydrophilic AOC AUC. L-AOC
      increased following a meal of blueberry containing 12.5 mmole TE AOC (Study #1).
      Consumption of 280 g of cherries (4.5 mmol TE AOC) increased plasma L-AOC but not
      H-AOC. The AOC in the control groups in which additional macronutrients (Studies
      #4 and #5) were added decreased from the postprandial baseline AOC measurement.
      CONCLUSION: We have demonstrated that consumption of certain berries and fruits
      such as blueberries, mixed grape and kiwifruit, was associated with increased
      plasma AOC in the postprandial state and consumption of an energy source of
      macronutrients containing no antioxidants was associated with a decline in plasma
      AOC. However, without further long term clinical studies, one cannot necessarily
      translate increased plasma AOC into a potential decreased risk of chronic
      degenerative disease. Preliminary estimates of antioxidant needs based upon
      energy intake were developed. Consumption of high antioxidant foods with each
      meal is recommended in order to prevent periods of postprandial oxidative stress.

PMID- 17536131
TI  - Medical education: the bottlenecks.

PMID- 17536130
TI  - Protein intake during energy restriction: effects on body composition and markers
      of metabolic and cardiovascular health in postmenopausal women.
AB  - OBJECTIVE: The primary aim of this study was to assess the effects of dietary
      protein intake on energy restriction (ER)-induced changes in body mass and body
      composition. Clinical markers of metabolic and cardiovascular diseases were also
      measured. DESIGN: 54 postmenopausal women, age 58 +/- 2 y, body mass index 29.6
      +/- 0.8 kg/m(2), were assigned to one of four groups. For 9 weeks, three ER
      groups ate a 1000 kcal/d lacto-ovo vegetarian basal diet plus 250 kcal/d of
      either beef (BEEF, n = 14), chicken (CHICKEN, n = 15), or carbohydrate/fat foods
      (CARB (lacto-ovo), n = 14), while a control group (CON, n = 11) consumed their
      habitual diets. RESULTS: Energy intake was lower in the ER groups compared to CON
      (BEEF, 1114 +/- 155 kcal/d, CHO: PRO: FAT, 46:24:30 % of energy intake; CHICKEN,
      1098 +/- 203 kcal/d, 51:25:24; CARB 1158 +/- 341 kcal/d, 59:17:24; CON, 1570 +/-
      633 kcal/d, 47:20:33), but did not differ among ER groups. For all ER subjects
      combined, body mass (-6.7 +/- 2.4 kg, 9 %), fat mass (-4.6 +/- 1.9 kg, 13 %), and
      fat-free mass (-2.1 +/- 1.1 kg, 5 %) decreased. These responses did not differ
      among the ER groups, except for body mass (CHICKEN -7.9 +/- 2.6 kg(a); BEEF -6.6
      +/- 2.7 kg(a,b); CARB -5.6 +/- 1.8 kg(b); CON -1.2 +/- 1.2 kg(c); values with a
      difference superscript differ, p < 0.05). From PRE (week 0) to POST (week 9),
      total and LDL cholesterol decreased approximately 12%, with no differences among
      groups. Triacylglycerol, HDL cholesterol, C-reactive protein (CRP), glucose,
      insulin, leptin, and adiponectin were not changed over time or differentially
      affected by diet. CONCLUSIONS: Overweight postmenopausal women can achieve
      significant weight loss and comparable short-term improvements in body
      composition and lipid-lipoprotein profile by consuming either a moderate-protein
      (25% of energy intake) poultry- or beef-containing diet or a lacto-ovo vegetarian
      protein (17% of energy intake) diet.

PMID- 17536132
TI  - Idiopathic pulmonary hemosiderosis: clinical profile and follow up of 26
      children.
AB  - OBJECTIVES: To describe the clinical details and follow up of children with
      idiopathic pulmonary hemosiderosis. DESIGN: Retrospective case series. SETTING:
      Pediatric chest clinic of a tertiary care hospital. SUBJECTS: Children diagnosed
      as suffering from idiopathic pulmonary hemosiderosis (IPH). METHODS: Charts of
      patients diagnosed as IPH were reviewed for clinical features and treatment
      regimen. Diagnosis was based on presence of iron deficiency anemia, chest
      radiography and demonstration of hemosiderin laden macrophages in bronchoalveolar
      lavage (BAL), gastric aspirate, or sputum. Treatment consisted of oral
      prednisolone, hydroxychloroquine (HCQ) and inhaled corticosteroids (ICS).
      RESULTS: The common clinical features in 26 children with IPH (mean age 75
      months) included: cough, breathlessness, fever, hemoptysis and wheezing in 26
      (100%), 22 (85%), 19 (73%),15 (58%) and 14 (54%) children, respectively.
      Clubbing, hepatomegaly and splenomegaly was seen in 16 (62%), 15 (58%) and 10
      (38%) children, respectively. Hemosiderin laden macrophages were documented in
      BAL and gastric aspirate in 92% and 30% patients, respectively. Symptoms did not
      recur in 17 patients who received prednisolone and HCQ initially. 5 patients had
      recurrence of symptoms and required short courses of oral prednisolone, 4
      patients required frequent courses of prednisolone and were started on
      azathioprine. Older age, longer duration of illness, history of hemoptysis and
      jaundice were associated with poor response. CONCLUSION: Treatment with
      prednisolone and hydroxychloroquine followed by inhaled corticosteroids may
      improve survival in children with IPH.

PMID- 17536133
TI  - Antiretroviral therapy in children: Indian experience.
AB  - BACKGROUND: There is a paucity of reports on Highly Active Antiretroviral therapy
      (HAART) in children. We studied feasibility and effectiveness fixed dose
      combination (FDC) of lamivudine, nevirapine and stavudine in HIV infected
      children. DESIGN: Interventional study. SETTING: A Tertiary care center.
      SUBJECTS: Twenty five consecutive HIV positive antiretroviral naive children
      older than 18 months. METHODS: The study subjects were started on weight
      appropriate doses of the FDC and followed up for 6 months. Weight, CD4 counts,
      absolute lymphocyte count (ALC) and number of episodes of illness were assessed
      before and after HAART. Adherence and barriers to adherence were studied.
      RESULTS: Mean weight increased from 15.2 to 16.8 kg (P < 0.001) while mean CD4
      counts increased from 488/cmm to 765/cmm (P < 0.001). Only 2 cases of drug
      associated adverse event were encountered. Improvement in Center for Disease
      Control (CDC) immunological classification of the subjects was significant while
      that in World Health Organization (WHO) clinical staging was not statistically
      significant. Follow up visits were 95% of the expected 175 visits. The average
      distance traveled by the patient for every visit was 72 km (one way).
      CONCLUSIONS: Use of FDC in weight specific dosages is feasible and effective for
      treatment of Pediatric HIV in resource scarce setting. These preliminary results
      need to be tested in a different setting.

PMID- 17536134
TI  - Comparison of the prevalence of tuberculosis infection in BCG vaccinated versus
      nonvaccinated school age children.
AB  - OBJECTIVE: To compare the prevalence of tuberculosis infection in BCG vaccinated
      versus non-vaccinated school age children in a tuberculosis endemic region.
      DESIGN: Cross-sectional, case control, school based survey. SETTING: Government
      lower primary school in Palakkad District, Kerala. METHODS: Tuberculosis
      infection was determined by tuberculin testing in 418 school children aged 5 to 9
      years, utilizing a differential outcome variable definition for BCG vaccinated
      and unvaccinated children, in a tuberculosis endemic area with moderate
      vaccination coverage. Nutritional status was calculated using weight for age and
      weight for height criteria. RESULTS: Tuberculin positivity rate in unvaccinated
      children (24%) was significantly higher than in the vaccinated (9.7%) (P<0.001,
      RR: 2.9). Overall prevalence rate of tuberculosis infection was 15.5%. Boys had
      significantly higher vaccination rates than girls (P < 0.001). No association was
      found between tuberculin reaction size and age or nutritional status.
      CONCLUSIONS: BCG vaccination is associated with significant protection against
      the acquisition of Mycobacterium tuberculosis infection in childhood. This
      finding highlights the importance of universal implementation of BCG vaccination
      in children in tuberculosis endemic regions.

PMID- 17536135
TI  - Insulin like growth factors and growth hormone deficiency.

PMID- 17536136
TI  - Zinc and copper in colostrum.
AB  - The Zn (Zinc) and Cu (Copper) contents of the first day milk from 117 Brazilian
      mothers were examined in relation to maternal age, parity and number of
      miscarriages. In parallel, household water was analyzed for the contents of the
      same trace elements. No significant relationship was found between levels of Zn
      and Cu and the aforementioned factors.

PMID- 17536137
TI  - Prevalence of eating disorders and psychiatric comorbidity among children and
      adolescents.
AB  - There are no prevalence or co-morbidity studies on eating disorders in India.
      This retrospective chart review studied the prevalence and psychiatric co
      morbidity among juveniles with eating disorders. Forty-one cases with ICD 10
      diagnosis of eating disorders were identified and analyzed. The prevalence of
      eating disorders was 1.25% Psychogenic vomiting was the commonest eating
      disorders and anorexia nervosa the emerging eating disorder. The most common co
      morbidities were depression, intellectual disability, and dissociative disorder.

PMID- 17536138
TI  - Recent advances in approach to treatment of genetic disorders: clinicians
      perspective.
AB  - There is no cure for most of the genetic disorders. The only option in most
      situations is prevention by counseling and prenatal diagnosis. However, over a
      decade, with the completion of the human genome project and other advances there
      is better understanding of pathogenesis, improvement in diagnostic strategies and
      various treatment avenues are opening up for these disorders. The aim of this
      article is to make the pediatricians aware of the approaches to treatment of
      common genetic disorders and recent available therapeutic interventions.

PMID- 17536139
TI  - An unusual cause of ascites: hemophagocytic lymphohistiocytosis.
AB  - Hemophagocytic lymphohistiocytosis is character-ized by fever,
      hepatosplenomegaly, cytopenia, hyper-triglyceridemia, hypofibrinogenemia, and
      hemophago-cytosis. Ascites is not mentioned as a symptom of hemophagocytic
      syndrome. We report a one month-old girl suffering from familial
      erythrophagocytic lympho-histiocytosis, who presented with ascites.

PMID- 17536140
TI  - Pneumococcal hemolytic uremic syndrome.
AB  - We report Hemolytic Uremic Syndrome (HUS) induced by Streptococcus pneumoniae in
      a 20 month-old girl. She responded well to hemodialysis.

PMID- 17536141
TI  - Two children with invasive gastrointestinal aspergillosis.
AB  - We report two immunocompromised infants aged six and four months with invasive
      gastrointestinal aspergillosis. Both patients presented with weight loss and
      diarrhea. The underlying disorders were combined immunodeficiency and transient
      hypogammaglobulinemia of infancy. The diagnosis of gastrointestinal aspergillosis
      was established by gastrointestinal endoscopy and histopathological examination
      of the tissue specimens. Both children responded well to Amphotericin B.

PMID- 17536142
TI  - Hemifacial seizures and cerebellar tumor: a rare co-existence.
AB  - We report a 4-year-old boy with multiple daily episodes of abnormal eye
      movements, hemifacial spasms. Neuro-imaging revealed a cerebellar tumor. We
      believe that this association constitutes a rare but important syndrome of
      epilepsy characterized by seizures of cerebellar origin.

PMID- 17536143
TI  - IAP Guidelines 2006 on management of acute diarrhea.

PMID- 17536144
TI  - IAP Committee on Immunization.

PMID- 17536146
TI  - The missing ball mystery.

PMID- 17536147
TI  - Factors predictive of remission in steroid resistant nephrotic syndrome in
      children: a multivariate analysis.

PMID- 17536148
TI  - Ethical and social implications of biometric identification technology.
AB  - This paper discusses the social and ethical aspects of biometrics, using mainly a
      historical approach. A description is provided as regards the origins and
      development of the word. Reference is made to the various ways in which it has
      been interpreted, sometimes very different one from another, and finally to the
      meaning currently attached to it. The most relevant ethical and social
      implications are highlighted by giving a brief overview of the contents of the
      main institutional documents produced both on an international and domestic level
      in the various countries. The analyses contained in these reports also bring to
      the fore the main challenges which society shall have to deal with, in the near
      future and on a long-term basis, as a consequence of the extremely rapid
      diffusion of those technologies which use biometric data request.

PMID- 17536149
TI  - Hey Buddy can you spare a DNA? New surveillance technologies and the growth of
      mandatory volunteerism in collecting personal information.
AB  - The new social surveillance can be defined as scrutiny through the use of
      technical means to extract or create personal or group data, whether from
      individuals or contexts. Examples include: video cameras; computer matching,
      profiling and data mining; work, computer and electronic location monitoring;
      biometrics; DNA analysis; drug tests; brain scans for lie detection; various
      forms of imaging to reveal what is behind walls and enclosures. There are two
      problems with the new surveillance technologies. One is that they don't work and
      the other is that they work too well. If the first, they fail to prevent
      disasters, bring miscarriages of justice, and waste resources. If the second,
      they can further inequality and invidious social categorization; they chill
      liberty. These twin threats are part of the enduring paradox of democratic
      government that must be strong enough to maintain reasonable order, but not so
      strong as to become undemocratic.

PMID- 17536150
TI  - Freedom, security and justice: the thin end of the wedge for biometrics?
AB  - This paper examines an area of EU policy where the application of information and
      communication tecnology (ICT) poses acutely difficult problems for policymakers:
      freedom, security and justice. It focuses on the absence of an ethical debate
      about the adoption of ICT-based instruments in this area. It highlights the
      implausibility of simply adopting codes of ethical practice from the health
      sector to close the public trust deficit. It argues that health and justice
      professionals need to cooperate in order to create a code of ethical e-governance
      fit for an e-governance age.

PMID- 17536151
TI  - Biometrics and international migration.
AB  - This paper will focus on the impact of the rapid expansion in the use of
      biometric systems in migration management on the rights of individuals; it seeks
      to highlight legal issues for consideration in implementing such systems, taking
      as the starting point that the security interests of the state and the rights of
      the individual are not, and should not be, mutually exclusive. The first part of
      this paper briefly describes the type of biometric applications available, how
      biometric systems function, and those used in migration management. The second
      part examines the potential offered by biometrics for greater security in
      migration management, and focuses on developments in the use of biometrics as a
      result of September 11. The third part discusses the impact of the use of
      biometrics in the management of migration on the individual's right to privacy
      and ability to move freely and lawfully. The paper highlights the increasing need
      for domestic and international frameworks to govern the use of biometric
      applications in the migration/security context, and proposes a number of issues
      that such frameworks could address.

PMID- 17536152
TI  - European securitization and biometric identification: the uses of genetic
      profiling.
AB  - The recent loss of confidence in textual and verbal methods for validating the
      identity claims of individual subjects has resulted in growing interest in the
      use of biometric technologies to establish corporeal uniqueness. Once
      established, this foundational certainty allows changing biographies and shifting
      category memberships to be anchored to unchanging bodily surfaces, forms or
      features. One significant source for this growth has been the "securitization"
      agendas of nation states that attempt the greater control and monitoring of
      population movement across geographical borders. Among the wide variety of
      available biometric schemes, DNA profiling is regarded as a key method for
      discerning and recording embodied individuality. This paper discusses the current
      limitations on the use of DNA profiling in civil identification practices and
      speculates on future uses of the technology with regard to its interoperability
      with other biometric databasing systems.

PMID- 17536153
TI  - Genetics, biometrics and the informatization of the body.
AB  - "Genetics" is a term covering a wide set of theories, practices, and
      technologies, only some of which overlap with the practices and technologies of
      biometrics. In this paper some current technological developments relating to
      biometric applications of genetics will be highlighted. Next, the author will
      elaborate the notion of the informatization of the body, by means of a brief
      philosophical detour on the dualisms of language and reality, words and things.
      In the subsequent sections she will then draw out some of the questions relevant
      to the purposes of Biometrics Identification Technology Ethics (BITE), and
      discuss the ethical problems associated with the informatization of the body.
      There are, however some problems and limitations to the currently dominant
      ethical discourse to deal with all things ethical in relation to information
      technology in general, and biometrics or genetics in particular. The final
      section will discuss some of these meta-problems.

PMID- 17536154
TI  - Body identification, biometrics and medicine: ethical and social considerations.
AB  - Identity is important when it is weak. This apparent paradox is the core of the
      current debate on identity. Traditionally, verification of identity has been
      based upon authentication of attributed and biographical characteristics. After
      small scale societies and large scale, industrial societies, globalization
      represents the third period of personal identification. The human body lies at
      the heart of all strategies for identity management. The tension between human
      body and personal identity is critical in the health care sector. The health care
      sector is second only to the financial sector in term of the number of biometric
      users. Many hospitals and healthcare organizations are in progress to deploy
      biometric security architecture. Secure identification is critical in the health
      care system, both to control logic access to centralized archives of digitized
      patients' data, and to limit physical access to buildings and hospital wards, and
      to authenticate medical and social support personnel. There is also an increasing
      need to identify patients with a high degree of certainty. Finally there is the
      risk that biometric authentication devices can significantly reveal any health
      information. All these issues require a careful ethical and political scrutiny.

PMID- 17536155
TI  - Biometrics between opacity and transparency.
AB  - The overall aim of the democratic constitutional state is to protect a social
      order in which the individual liberty of the citizen is a major concern. As a
      consequence the democratic constitutional state should guarantee simultaneously
      and paradoxically a high level of individual freedom and an order in which such
      freedom is made possible and guaranteed. Biometrics provide a strong and
      expressive example both of the necessity to address the issue of opacity and
      transparency and the complexity of the process. Indeed, the large scale use of
      biometrics does not only question the position of the individual in society, but
      it also alters the architecture or nature of this society as such.

PMID- 17536156
TI  - Collaborative study for the calibration of HCV RNA, HBV DNA and HIV RNA reference
      preparations against the relative international standards.
AB  - We organised a collaborative study to calibrate three new ISS reference
      preparations (ISS: Istituto Superiore di Sanita), one for HCV RNA, one for HIV
      RNA and one for HBV DNA, to be used for nucleic acid amplification techniques
      (NAT) in blood testing. Serial dilution of the ISS reference preparations and the
      respective international standards were tested in different days by each
      participating laboratory using two commercial NAT assays. Data were collected by
      the ISS for statistical analysis. Based on the mean potency of the HCV RNA and
      HIV RNA preparations, calculated from the results provided by the 12
      participating laboratories, a definitive concentrations of 5700 IU/mL and 4000
      IU/mL, respectively, were assigned to the reference materials. On the contrary,
      it was not possible to obtain a consensus titre for the HBV DNA reference
      material. These new Italian reference preparations (HCV RNA ISS/1005 and HIV RNA
      ISS/1005) calibrated against the respective international standards are available
      free of charge to any laboratory upon request.

PMID- 17536157
TI  - Influence of family history of type 2 diabetes on leptin concentration in cord
      blood of male offspring with high birth weight.
AB  - To verify whether a diabetes family history might be a risk factor for the
      development, in adult age, of metabolic disorders, leptin, anthropometric and
      endocrine parameters were analysed in 95 babies with grandparents affected by
      type 2 diabetes (DF) and in 95 matched babies without diabetes family history
      (NDF). A sexual dimorphism for leptin was present in the NDF group (males: 6.7+/
      4.1 ng/ml; females: 12.3+/-6.5; p < 0.0001) but not in the DF group (males: 9.0+/
      5.5; females: 10.8+/-6.4), due to the significant increase in DF male leptin
      level, compared to that of NDF males (p < 0.05). In DF males only, leptin was
      positively correlated with body length, PI, C-peptide, IGF-1 and IGF1BP3. These
      results suggest that the increase in DF male leptin could be a compensatory
      mechanism for reduced insulin sensitivity in a pre-clinical alteration of glucose
      metabolism.

PMID- 17536158
TI  - Molecular findings and antibiotic-resistance in an outbreak of Acinetobacter
      baumannii in an intensive care unit.
AB  - We investigated an outbreak of Acinetobacter baumannii in the intensive care unit
      (ICU) of a hospital in Rome, Italy. The outbreak involved 14 patients whose
      isolates were most frequently recovered from bronchoalveolar lavage. All isolates
      were multidrug-resistant and showed diminished susceptibility or resistance to
      carbapenems. A. baumannii strains with a similar antibiotic susceptibility
      pattern were isolated from the environment. Pulsed-field gel electrophoresis
      identified a single clone from both the patients' and environmental isolates.
      Because of the lack of a single source of infection, the eradication of the
      epidemic required a broad approach, including contact isolation and cohorting,
      aggressive environmental disinfection, and close monitoring of the ward staff's
      performance. Infected patients were successfully treated with combined therapy.
      Although considered of low virulence, A. baumannii can be particularly aggressive
      and difficult to treat in ICU patients.

PMID- 17536159
TI  - Engineering aspects of stents design and their translation into clinical
      practice.
AB  - The implantation of coronary stents is a relevant part of interventional
      procedures for percutaneous revascularization. The wide acceptance of coronary
      stenting was based on the results of two highly significant trials which have
      shown the superiority of stenting over balloon angioplasty in terms of reduction
      of angiographic restenosis and need for repeated intervention in focal lesions
      and large coronary arteries. Since then, the growing use of stent market was
      impressive. A rapidly increasing number of different stent type with different
      material and designs has been introduced in the market both for bare metal stent
      and drug eluting stent. This review will summarize the different components of
      stent design that are important in term of biological response of the arterial
      wall and clinical outcome. In addition, new stent platforms, mainly represented
      by the biodegradable stent will be shortly reviewed since it may provide in the
      near future a more "physiological" answer to stent implantation, reducing
      vascular injury and accelerating vessel healing with consequent improving in
      clinical outcome.

PMID- 17536160
TI  - A telemedicine instrument for home monitoring of patients with chronic
      respiratory diseases.
AB  - We developed a telemedicine instrument for home monitoring of subjects with
      respiratory diseases. The instrument directly measures blood oxygen saturation
      and pulse rate, but the most relevant aspect is that it also acts as digital
      recorder of parameters coming from several external instruments (spirometer,
      capnometer, NIBP device, etc.). It also connects to all pulmonary ventilators.
      The instrument main board includes five slots, which are used to insert the
      measuring boards (saturation and ventilation boards) and the interface boards
      (connecting the external instruments). Depending on patient's needs, only the
      proper measuring/interface boards are mounted, thus allowing maximum flexibility
      and cost saving. The instrument has several I/O units, and especially an internal
      modem for direct connection to the Internet through TCP/IP protocol. The
      instrument was extensively tested, and preliminary trials were performed over
      fifteen patients with amyotrophic lateral sclerosis.

PMID- 17536161
TI  - Smokable ("ice", "crystal meth") and non smokable amphetamine-type stimulants:
      clinical pharmacological and epidemiological issues, with special reference to
      the UK.
AB  - "Ice", "crystal meth", is the smokable form of methamphetamine hydrochloride.
      This paper will comment on the pharmacological, epidemiological, clinical and
      social issues related to smoking the drug as opposed to either its injection or
      ingestion. Furthermore, some data related to amphetamines/methamphetamines
      consumption, request for treatment, seizures, related offences and deaths in the
      UK (1990-2002) will be offered here. Peak rates, for most indicators, were
      reached at the end of the '90s, to fall down in the following years. The only
      indicator which seemed not to show any declining rates is number of deaths, but
      this may be related to a more general increase in stimulant death rates recently
      observed in the UK. It is argued that methamphetamines, and particularly "crystal
      meth", could reach the same prevalence levels of use in the UK as it is already
      in the US but recent reclassification of the drug to Class A in the UK could help
      to better control this emerging issue.

PMID- 17536162
TI  - Key issues in achieving an integrative perspective on stress.
AB  - An integrative perspective on molecular mechanisms of stress resistance requires
      understanding of these mechanisms not just in vitro or in the model organism in
      the research laboratory - but in the healthy or diseased human in society,in the
      cultivated plant or animal in agricultural production,and in populations and
      species in natural communities and ecosystems. Such understanding involves
      careful attention to the context in which the organism normally undergoes
      stress,and appreciation that biological phenomena occur at diverse levels of
      organization (from molecule to ecosystem). Surprisingly,three issues fundamental
      to achieving an integrative perspective are presently unresolved: (i) Is
      variation in lower-level traits (nucleotide sequences, genes, gene products)
      seldom, commonly, or always consequential for stress resistance? (ii) Does
      environmental stress reduce or enhance genetic variation, which is the raw
      material of evolution? (iii) Is the present distribution of organisms along
      natural gradients of stress largely the result of organisms living where they
      can, or is adaptive evolution generally sufficient to overcome stress? Effective
      collaboration among disciplinary specialists and meta-analysis may be helpful in
      resolving these issues.

PMID- 17536163
TI  - Molecular chaperones: the modular evolution of cellular networks.
AB  - Molecular chaperones play a prominent role in signaling and transcriptional
      regulatory networks of the cell. Recent advances uncovered that chaperones act as
      genetic buffers stabilizing the phenotype of various cells and organisms and may
      serve as potential regulators of evolvability. Chaperones have weak links,
      connect hubs, are in the overlaps of network modules and may uncouple these
      modules during stress,which gives an additional protection for the cell at the
      network-level. Moreover,after stress chaperones are essential to re-build inter
      modular contacts by their low affinity sampling of the potential interaction
      partners in different modules. This opens the way to the chaperone-regulated
      modular evolution of cellular networks,and helps us to design novel therapeutic
      and anti-aging strategies.

PMID- 17536164
TI  - Studying stress responses in the post-genomic era: its ecological and
      evolutionary role.
AB  - Most investigations on the effects of and responses to stress exposures have been
      performed on a limited number of model organisms in the laboratory. Here much
      progress has been made in terms of identifying and describing beneficial and
      detrimental effects of stress, responses to stress and the mechanisms behind
      stress tolerance. However, to gain further understanding of which genes are
      involved in stress resistance and how the responses are regulated from an
      ecological and evolutionary perspective there is a need to combine studies on
      multiple levels of biological organization from DNA to phenotypes. Furthermore,we
      emphasize the importance of studying ecologically relevant traits and natural or
      semi-natural conditions to verify whether the results obtained are representative
      of the ecological and evolutionary processes in the field. Here,we will review
      what we currently know about thermal adaptation and the role of different stress
      responses to thermal challenges in insects, particularly
      Drosophila.Furthermore,we address some key questions that require future
      attention.

PMID- 17536165
TI  - Molecular mechanisms of canalization: Hsp90 and beyond.
AB  - The Hsp90 chaperone machine facilitates the maturation of a diverse set of
      'client' proteins. Many of these Hsp90 clients are essential nodes in signal
      transduction pathways and regulatory circuits,accounting for the important role
      Hsp90 plays in organismal development and responses to the environment. Recent
      findings suggest a broader impact of the chaperone on phenotype: fully functional
      Hsp90 canalizes wild-type phenotypes by suppressing underlying genetic and
      epigenetic variation. This variation can be expressed upon challenging the Hsp90
      machinery by environmental stress, genetic or pharmaceutical targeting of Hsp90.
      The existence of Hsp90-buffered genetic and epigenetic variation together with
      plausible release mechanisms has wide-ranging implication for phenotype and
      possibly evolutionary processes. Here,we discuss the role of Hsp90 in
      canalization and organismal plasticity,and highlight important questions for
      future experimental inquiry.

PMID- 17536166
TI  - Developmental plasticity and acclimation both contribute to adaptive responses to
      alternating seasons of plenty and of stress in Bicyclus butterflies.
AB  - Plasticity is a crucial component of the life cycle of invertebrates that live as
      active adults throughout wet and dry seasons in the tropics. Such plasticity is
      seen in the numerous species of Bicyclus butterflies in Africa which exhibit
      seasonal polyphenism with sequential generations of adults with one or other of
      two alternative phenotypes. These differ not only in wing pattern but in many
      other traits. This divergence across a broad complex of traits is associated with
      survival and reproduction either in a wet season that is favourable in terms of
      resources, or mainly in a dry season that is more stressful. This phenomenon has
      led us to examine the bases of the developmental plasticity in a model species,
      B.anynana, and also the evolution of key adult life history traits, including
      starvation resistance and longevity. We now understand something about the
      processes that generate variation in the phenotype,and also about the ecological
      context of responses to environmental stress. The responses clearly involve a mix
      of developmental plasticity as cued by different environments in pre-adult
      development,and the acclimation of life history traits in adults to their
      prevailing environment.

PMID- 17536168
TI  - Molecular mechanisms underlying thermal adaptation of xeric animals.
AB  - For many years,we and our collaborators have investigated the adaptive role of
      heat shock proteins in different animals,including the representatives of
      homothermic and poikilothermic species that inhabit regions with contrasting
      thermal conditions. Adaptive evolution of the response to hyperthermia has led to
      different results depending upon the species. The thermal threshold of induction
      of heat shock proteins in desert thermophylic species is, as a rule, higher than
      in the species from less extreme climates. In addition,thermoresistant
      poikilothermic species often exhibit a certain level of heat shock proteins in
      cells even at a physiologically normal temperature. Furthermore,there is often a
      positive correlation between the characteristic temperature of the ecological
      niche of a given species and the amount of Hsp70-like proteins in the cells at
      normal temperature. Although in most cases adaptation to hyperthermia occurs
      without changes in the number of heat shock genes, these genes can be amplified
      in some xeric species. It was shown that mobile genetic elements may play an
      important role in the evolution and fine-tuning of the heat shock response
      system,and can be used for direct introduction of mutations in the promoter
      regions of these genes.

PMID- 17536167
TI  - The role of stress proteins in responses of a montane willow leaf beetle to
      environmental temperature variation.
AB  - The heat shock response is a critical mechanism by which organisms buffer effects
      of variable and unpredictable environmental temperatures. Upregulation of heat
      shock proteins (Hsps) increases survival after exposure to stressful conditions
      in nature, although benefits of Hsp expression are often balanced by costs to
      growth and reproductive success. Hsp-assisted folding of variant polypeptides may
      prevent development of unfit phenotypes; thus, some differences in Hsp expression
      among natural populations of ectotherms may be due to interactions between enzyme
      variants (allozymes) and Hsps. In the Sierra willow leaf beetle Chrysomela
      aeneicollis, which lives in highly variable thermal habitats at the southern edge
      of their range in the Eastern Sierra Nevada, California, allele frequencies at
      the enzyme locus phosphoglucose isomerase (PGI) vary across a climatic
      latitudinal gradient. PGI allozymes differ in kinetic properties,and expression
      of a 70 kDa Hsp differs between populations, along elevation gradients,and among
      PGI genotypes. Differences in Hsp70 expression among PGI genotypes correspond to
      differences in thermal tolerance and traits important for reproductive success,
      such as running speed, survival and fecundity. Thus, differential Hsp expression
      among genotypes may allow functionally important genetic variation to persist,
      allowing populations to respond effectively to environmental change.

PMID- 17536169
TI  - Specific and unspecific responses of plants to cold and drought stress.
AB  - Different environmental stresses to a plant may result in similar responses at
      the cellular and molecular level. This is due to the fact that the impacts of the
      stressors trigger similar strains and downstream signal transduction chains. A
      good example for an unspecific response is the reaction to stressors which induce
      water deficiency e.g.drought, salinity and cold, especially frost. The
      stabilizing effect of liquid water on the membrane bilayer can be supported by
      compatible solutes and special proteins. At the metabolic level, osmotic
      adjustment by synthesis of low-molecular osmolytes (carbohydrates, betains,
      proline) can counteract cellular dehydration and turgor loss. Taking the example
      of Pinus sylvestris, changes at the level of membrane composition, and
      concomitantly of photosynthetic capacity during frost hardening is shown.
      Additionally the effect of photoperiod as measured via the phytochrome system and
      the effect of subfreezing temperatures on the incidence of frost hardening is
      discussed. Extremely hydrophilic proteins such as dehydrins are common products
      protecting not only the biomembranes in ripening seeds (late embryogenesis
      abundant proteins)but accumulate also in the shoots and roots during cold
      adaptation, especially in drought tolerant plants. Dehydrins are characterized by
      conserved amino acid motifs, called the K-,Y-or S-segments. Accumulation of
      dehydrins can be induced not only by drought, but also by cold,salinity,treatment
      with abscisic acid and methyl jasmonate. Positive effects of the overexpression
      of a wild chickpea (Cicer pinnatifidum) dehydrin in tobacco plants on the
      dehydration tolerance is shown. The presentation discusses the perception of cold
      and drought,the subsequent signal transduction and expression of genes and their
      products. Differences and similarities between the plant responses to both
      stressors are also discussed.

PMID- 17536170
TI  - Protein stress and stress proteins: implications in aging and disease.
AB  - Environmental stress induces damage that activates an adaptive response in any
      organism. The cellular stress response is based on the induction of
      cytoprotective proteins,the so called stress or heat shock proteins. The stress
      response as well as stress proteins are ubiquitous,highly conserved mechanism,
      and genes, respectively, already present in prokaryotes. Chaperones protect the
      proteome against conformational damage, promoting the function of protein
      networks. Protein damage takes place during aging and in several degenerative
      diseases, and presents a threat to overload the cellular defense mechanisms. The
      preservation of a robust stress response and protein disposal is indispensable
      for health and longevity. This review summarizes the present knowledge of protein
      damage, turnover, and the stress response in aging and degenerative diseases.

PMID- 17536172
TI  - Three-dimensional structure of heat shock protein 90 from Plasmodium falciparum:
      molecular modelling approach to rational drug design against malaria.
AB  - We have recently implicated heat shock protein 90 from Plasmodium falciparum
      (PfHsp90) as a potential drug target against malaria. Using inhibitors specific
      to the nucleotide binding domain of Hsp90, we have shown potent growth inhibitory
      effects on development of malarial parasite in human erythrocytes. To gain better
      understanding of the vital role played by PfHsp90 in parasite growth,we have
      modeled its three dimensional structure using recently described full length
      structure of yeast Hsp90.S equence similarity found between PfHsp90 and yeast
      Hsp90 allowed us to model the core structure with high confidence. The
      superimposition of the predicted structure with that of the template yeast Hsp90
      structure reveals an RMSD of 3.31 Angstrom. The N-terminal and middle domains
      showed the least RMSD (1.76 Angstrom) while the more divergent C-terminus showed
      a greater RMSD (2.84 Angstrom) with respect to the template. The structure shows
      overall conservation of domains involved in nucleotide binding, ATPase activity,
      co-chaperone binding as well as inter-subunit interactions. Important co
      chaperones known to modulate Hsp90 function in other eukaryotes are conserved in
      malarial parasite as well. An acidic stretch of amino acids found in the linker
      region, which is uniquely extended in PfHsp90 could not be modeled in this
      structure suggesting a flexible conformation. Our results provide a basis to
      compare the overall structure and functional pathways dependent on PfHsp90 in
      malarial parasite. Further analysis of differences found between human and
      parasite Hsp90 may make it possible to design inhibitors targeted specifically
      against malaria.

PMID- 17536171
TI  - Heat shock protein 90: the cancer chaperone.
AB  - Heat shock protein 90 (Hsp90) is a molecular chaperone required for the stability
      and function of a number of conditionally activated and/or expressed signalling
      proteins, as well as multiple mutated, chimeric, and/or over-expressed signalling
      proteins, that promote cancer cell growth and/or survival. Hsp90 inhibitors are
      unique in that, although they are directed towards a specific molecular target,
      they simultaneously inhibit multiple cellular signalling pathways. By inhibiting
      nodal points in multiple overlapping survival pathways utilized by cancer cells,
      combination of an Hsp90 inhibitor with standard chemotherapeutic agents may
      dramatically increase the in vivo efficacy of the standard agent. Hsp90
      inhibitors may circumvent the characteristic genetic plasticity that has allowed
      cancer cells to eventually evade the toxic effects of most molecularly targeted
      agents. The mechanism-based use of Hsp90 inhibitors, both alone and in
      combination with other drugs, should be effective toward multiple forms of
      cancer. Further, because Hsp90 inhibitors also induce Hsf-1-dependent expression
      of Hsp70, and because certain mutated Hsp90 client proteins are neurotoxic, these
      drugs display ameliorative properties in several neurodegenerative disease
      models, suggesting a novel role for Hsp90 inhibitors in treating multiple
      pathologies involving neurodegeneration.

PMID- 17536173
TI  - Polyglutamine expansion in Drosophila: thermal stress and Hsp70 as selective
      agents.
AB  - Repetitive DNA sequences that encode polyglutamine tracts are prone to expansion
      and cause highly deleterious phenotypes of neurodegeneration. Despite this
      tendency,polyglutamine tracts ("polyQs") are conserved features of eukaryotic
      genomes. PolyQs are the most frequent protein-coding homotypic repeat in insect
      genomes, and are found predominantly in genes encoding transcription factors
      conserved from Drosophila through human. Although highly conserved across
      species, polyQ lengths vary widely within species. In D. melanogaster, polyQs in
      25 genes have more alleles and higher heterozygosity than all other poly-amino
      acid tracts. The heat shock protein Hsp70 is a principal suppressor of polyQ
      expansions and may play a key role in modulating the phenotypes of the alleles
      that encode them. Hsp70 also promotes tolerance of natural thermal stress in
      Drosophila and diverse organisms,a role which may deplete the chaperone from
      buffering against polyQ toxicity. Thus in stressful environments, natural
      selection against long polyQ alleles more prone to expansion and deleterious
      phenotypes may be more effective. This hypothesis can be tested by measuring the
      phenotypic interactions between Hsp70 and polyQ transgenes in D. melanogaster
      undergoing natural thermal stress, an approach which integrates comparative
      genomics with experimental and ecological genetics.

PMID- 17536174
TI  - Thermosensors in eubacteria: role and evolution.
AB  - Temperature is an important physical stress factor sensed by bacteria and used to
      regulate gene expression. Three different macromolecules have been identified
      being able to sense temperature: DNA, mRNA and proteins. Depending on the
      induction mechanism, two different pathways have to be distinguished, namely the
      heat shock response and the high temperature response. While the heat shock
      response is induced by temperature increments and is transient, the high
      temperature response needs a specific temperature to become induced and proceeds
      as long as cells are exposed to that temperature. The heat shock response is
      induced by denatured proteins and aimed to prevent formation of protein
      aggregates by refolding or degradation, and the high temperature response is
      mainly used by pathogenic bacteria to detect entry into a mammalian host followed
      by induction of their virulence genes. All known high temperature sensors are
      present in two alternative conformations depending on the temperature. Heat shock
      sensors are either molecular chaperones or proteases which keep either a positive
      transcriptional regulator inactive or a negative regulator active or do not
      attack the regulator, respectively, under physiological conditions. Denatured
      proteins either titrate the molecular chaperones or activate the protease. The
      evolution of the different temperature sensors is discussed.

PMID- 17536175
TI  - The Kdp-ATPase system and its regulation.
AB  - K+, the dominant intracellular cation, is required for various physiological
      processes like turgor homeostasis, pH regulation etc. Bacterial cells have
      evolved many diverse K+ transporters to maintain the desired concentration of
      internal K+. In E.coli, the KdpATPase (comprising of the KdpFABC complex),
      encoded by the kdpFABC operon, is an inducible high-affinity K+ transporter that
      is synthesised under conditions of severe K+ limitation or osmotic upshift. The
      E.coli kdp expression is transcriptionally regulated by the KdpD and KdpE
      proteins, which together constitute a typical bacterial two-component signal
      transduction system. The Kdp system is widely dispersed among the different
      classes of bacteria including the cyanobacteria. The ordering of the kdpA, kdpB
      and kdpC is relatively fixed but the kdpD/E genes show different arrangements in
      distantly related bacteria. Our studies have shown that the cyanobacterium
      Anabaena sp. strain L-31 possesses two kdp operons, kdp1 and kdp2, of which, the
      later is expressed under K+ deficiency and desiccation. Among the regulatory
      genes,the kdpD ORF of Anabaena L-31 is truncated when compared to the kdpD of
      other bacteria, while a kdpE -like gene is absent. The extremely radio-resistant
      bacterium, Deinococcus radiodurans strain R1, also shows the presence of a
      naturally short kdpD ORF similar to Anabaena in its kdp operon. The review
      elaborates the expression of bacterial kdp operons in response to various
      environmental stress conditions, with special emphasis on Anabaena. The possible
      mechanism(s)of regulation of the unique kdp operons from Anabaena and Deinococcus
      are also discussed.

PMID- 17536176
TI  - Basal transcription machinery: role in regulation of stress response in
      eukaryotes.
AB  - The holoenzyme of prokaryotic RNA polymerase consists of the core enzyme, made of
      two alpha, beta, beta' and omega subunits, which lacks promoter selectivity and a
      sigma (sigma) subunit which enables the core enzyme to initiate transcription in
      a promoter dependent fashion. A stress sigma factor sigma(s), in prokaryotes
      seems to regulate several stress response genes in conjunction with other stress
      specific regulators. Since the basic principles of transcription are conserved
      from simple bacteria to multicellular complex organisms, an obvious question is:
      what is the identity of a counterpart of sigma(s), that is closest to the core
      polymerase and that dictates transcription of stress regulated genes in general?
      In this review, we discuss the logic behind the suggestion that like in
      prokaryotes,eukaryotes also have a common functional unit in the transcription
      machinery through which the stress specific transcription factors regulate rapid
      and highly controlled induction of gene expression associated with generalized
      stress response and point to some candidates that would fit the bill of the
      eukaryotic sigma(s).

PMID- 17536177
TI  - Mechanisms of HSP72 release.
AB  - Currently two mechanisms are recognized by which heat shock proteins (HSP) are
      released from cells; a passive release mechanism, including necrotic cell death,
      severe blunt trauma, surgery and following infection with lytic viruses, and an
      active release mechanism which involves the non classical protein release
      pathway. HSPs are released both as free HSP and within exosomes. This review
      covers recent findings on the mechanism by which stress induces the release of
      HSP72 into the circulation and the biological significance of circulating HSP72
      to host defense against disease.

PMID- 17536178
TI  - Heat shock transcription factors regulate heat induced cell death in a rat
      histiocytoma.
AB  - Heat shock response is associated with the synthesis of heat shock proteins
      (Hsps) which is strictly regulated by different members of heat shock
      transcription factors (HSFs). We previously reported that a rat histiocytoma, BC
      8 failed to synthesize Hsps when subjected to typical heat shock conditions (42
      degrees C, 60 min). The lack of Hsp synthesis in these cells was due to a failure
      in HSF1 DNA binding activity. In the present study we report that BC-8 tumor
      cells when subjected to heat shock at higher temperature (43 degrees C, 60 min)
      or incubation for longer time at 42 degrees C, exhibited necrosis
      characteristics; however,under mild heat shock (42 degrees C, 30 min) conditions
      cells showed activation of autophagy. Mild heat shock treatment induced
      proteolysis of HSF1, and under similar conditions we observed an increase in HSF2
      expression followed by its enhanced DNA binding activity. Inhibiting HSF1
      proteolysis by reversible proteasome inhibition failed to inhibit heat shock
      induced autophagy. Compromising HSF2 expression but not HSF1 resulted in the
      inhibition of autophagy, suggesting HSF2 dependent activation of autophagy. We
      are reporting for the first time that HSF2 is heat inducible and functions in
      heat shock induced autophagic cell death in BC-8 tumor cells.

PMID- 17536179
TI  - Heat shock genes - integrating cell survival and death.
AB  - Heat shock induced gene expression and other cellular responses help limit the
      damage caused by stress and thus facilitate cellular recovery. Cellular damage
      also triggers apoptotic cell death through several pathways. This paper briefly
      reviews interactions of the major heat shock proteins with components of the
      apoptotic pathways. Hsp90, which acts as a chaperone for unstable signal
      transducers to keep them poised for activation, interacts with RIP and Akt and
      promotes NF-kappa B mediated inhibition of apoptosis; in addition it also blocks
      some steps in the apoptotic pathways. Hsp70 is mostly anti-apoptotic and acts at
      several levels like inhibition of translocation of Bax into mitochondria, release
      of cytochrome c from mitochondria,formation of apoptosome and inhibition of
      activation of initiator caspases. Hsp70 also modulates JNK,NF-kappa B and Akt
      signaling pathways in the apoptotic cascade. In contrast, Hsp60 has both anti-and
      pro-apoptotic roles. Cytosolic Hsp60 prevents translocation of the pro-apoptotic
      protein Bax into mitochondria and thus promotes cell survival but it also
      promotes maturation of procaspase-3,essential for caspase mediated cell death.
      Our recent in vivo studies show that RNAi for the Hsp60D in Drosophila
      melanogaster prevents induced apoptosis. Hsp27 exerts its anti-apoptotic
      influence by inhibiting cytochrome c and TNF-mediated cell death. alpha beta
      crystallin suppresses caspase-8 and cytochrome c mediated activation of caspase
      3. Studies in our laboratory also reveal that absence or reduced levels of the
      developmentally active as well as stress induced non-coding hsr omega
      transcripts, which are known to sequester diverse hnRNPs and related nuclear RNA
      binding proteins,block induced apoptosis in Drosophila. Modulation of the
      apoptotic pathways by Hsps reflects their roles as "weak links" between various
      "hubs" in cellular networks. On the other hand, non-coding RNAs, by virtue of
      their potential to bind with multiple proteins,can act as "hubs" in these
      networks. In view of the integrative nature of living systems, it is not
      surprising that stress-induced genes,generally believed to primarily function in
      cell survival pathways, inhibit or even promote cell death pathways at multiple
      levels to ensure homeostasis at cell and/or organism level. The heat shock genes
      obviously do much more than merely help cells survive stress.

PMID- 17536180
TI  - Complexity of rice Hsp100 gene family: lessons from rice genome sequence data.
AB  - Elucidation of genome sequence provides an excellent platform to understand
      detailed complexity of the various gene families. Hsp100 is an important family
      of chaperones in diverse living systems. There are eight putative gene loci
      encoding for Hsp100 proteins in Arabidopsis genome. In rice, two full-length
      Hsp100 cDNAs have been isolated and sequenced so far. Analysis of rice genomic
      sequence by in silico approach showed that two isolated rice Hsp100 cDNAs
      correspond to Os05g44340 and Os02g32520 genes in the rice genome database. There
      appears to be three additional proteins (encoded by Os03g31300, Os04g32560 and
      Os04g33210 gene loci) that are variably homologous to Os05g44340 and Os02g32520
      throughout the entire amino acid sequence. The above five rice Hsp100 genes show
      significant similarities in the signature sequences known to be conserved among
      Hsp100 proteins. While Os05g44340 encodes cytoplasmic Hsp100 protein, those
      encoded by the other four genes are predicted to have chloroplast transit
      peptides.

PMID- 17536181
TI  - Functional validation of a novel isoform of Na+/H+ antiporter from Pennisetum
      glaucum for enhancing salinity tolerance in rice.
AB  - Salt stress is an environmental factor that severely impairs plant growth and
      productivity. We have cloned a novel isoform of a vacuolar Na+/H+ antiporter from
      Pennisetum glaucum (PgNHX1) that contains 5 transmembrane domains in contrast to
      AtNHX1 and OsNHX1 which have 9 transmembrane domains. Recently we have shown that
      PgNHX1 could confer high level of salinity tolerance when overexpressed in
      Brassica juncea. Here,we report the functional validation of this antiporter in
      crop plant rice. Overexpression of PgNHX1 conferred high level of salinity
      tolerance in rice. Transgenic rice plants overexpressing PgNHX1 developed more
      extensive root system and completed their life cycle by setting flowers and seeds
      in the presence of 150 mM NaCl. Our data demonstrate the potential of PgNHX1 for
      imparting enhanced salt tolerance capabilities to salt-sensitive crop plants for
      growing in high saline areas.

PMID- 17536182
TI  - Acute effects of fast neutron irradiation on mouse liver.
AB  - Until now, the multiple biological effects of ionizing radiation on liver have
      been reported. However, there has not been any reports of fast neutron-mediated
      liver injuries including liver regeneration or fibrosis. Here, we described the
      biological effects of acute fast neutron irradiation on the liver. After the fast
      neutron irradiation of 0, 0.25, 1, 2, 4 and 8 Gy on mice, hepatocyte necrosis and
      a decrease in the total number of hepatocytes were induced dose-dependently.
      Binucleated hepatocytes and PCNA positive hepatocytes increased significantly at
      0.25 and 1 Gy, but decreased markedly at 2, 4 and 8 Gy. The expression of
      cytochrome P450 2E1 (CYP2E1) showed a dose-dependent increase after fast neutron
      irradiation. The activation of p-Smad2/3, signaling intermediates of transforming
      growth factor-beta (TGF-beta), increased in hepatocytes after exposure of 0.25,
      1, and 2 Gy of fast neutrons, but it was not detected in hepatic stellate cells
      (HSCs). In conclusion, fast neutron-induced liver damages, likely loss of
      hepatocytes, necrotic foci and vacuolar changes, were note on the dose dependent
      manner and hepatocellular regeneration were significantly diminished at doses of
      2, 4 and 8Gy in a dose-dependent manner. These alterations may at least in part
      be associated with dose-dependent increase in CYP2E1 and p-Smad2/3. These results
      show promise as an approach for the treatment of fast neutrons on liver tumors
      and in the study of pathogenesis regarding the fast neutron-irradiated damages of
      the liver.

PMID- 17536183
TI  - Effects of fibroblast growth factor-2 on the in vitro culture of caprine
      preantral follicles.
AB  - The aims of the present study were to evaluate the effects of fibroblast growth
      factor-2 (FGF-2) on survival, activation and growth of caprine early-staged
      (preantral) follicles using histological and ultrastructural studies. Fragments
      of caprine ovarian cortex were cultured for 1 or 5 days in an enriched minimum
      essential medium, supplemented or not with different concentrations of FGF-2 (10,
      50 or 100 ng/ml). Fragments from non-cultured ovarian tissue (control) and from
      tissues cultured for 1 or 5 days in a specific medium were processed for
      transmission electron microscopy (TEM) or classical histology to evaluate the
      morphological quality of caprine preantral follicles and to calculate the
      percentages of normal follicles. Additionally, effects of FGF-2 on oocyte and
      follicle diameter of cultured preantral follicles were investigated. Our results
      showed that, although the percentages of histologically normal follicles were
      lower in cultured than in non-cultured ovarian tissue fragments, there were no
      differences in this regard among treatments, neither on day 1 nor on day 5 of
      culture. After 1 and 5 days of culture, a significantly higher percentage of
      growing follicles was observed in the medium supplemented with 50 ng/ml of FGF-2.
      This FGF-2 treatment furthermore resulted in an increase in diameter of both
      oocytes and follicles that were cultured for 5 days. TEM showed that the
      ultrastructural integrity of caprine preantral follicles was maintained during
      their 5-day culture in the presence of 50 ng/ml FGF-2. In conclusion, this study
      demonstrated that at a concentration of 50 ng/ml FGF-2 not only maintains the
      morphological integrity of caprine preantral follicles cultured for 5 days, but
      also stimulates the activation of primordial follicles and the growth of
      activated follicles.

PMID- 17536184
TI  - Idiopathic organizing pneumonia: a relapsing disease. 19 years of experience in a
      hospital setting.
AB  - BACKGROUND: Although organizing pneumonia (OP) is a common pathological finding,
      studies including a substantial number of patients with idiopathic forms from a
      unique center and a long follow-up are rare. OBJECTIVES: To determine patients
      with cryptogenic forms of organizing pneumonia (COP), in order to characterize
      their clinical course, to identify predictive factors for relapse and to assess
      their effect on outcome. METHODS: For a 19-year period, all histopathological
      reports from a community teaching hospital were reviewed, and OP was found in 210
      lung specimens belonging to 197 patients. RESULTS: Thirty-three (17%) patients
      presented cryptogenic forms and 32 of them (97%) responded to steroid therapy. At
      follow-up, 14 patients presented no relapses (no-relapse group, NR) and 18 (56%)
      presented relapses (relapsing group, RG) that resolved with ulterior treatment.
      Multifocal opacities on chest X-ray (RG 83% vs. NR 36%, p = 0.02) appeared to be
      a predictor for relapse. Patients with relapses showed a shorter time span to
      chest X-ray normalization (RG 8 +/- 8 weeks vs. NR 13 +/- 9 weeks, p = 0.09) that
      became significant in patients with 3 or more relapses (multiple-relapse group,
      MR, 4 +/- 2 weeks vs. NR 13 +/- 9 weeks, p < 0.04). Although the initial
      prednisone dose was similar in patients with relapsing forms, its maintenance was
      shorter than in patients without relapses, showing a trend to significance (RG 4
      +/- 3 weeks, NR 7 +/- 6 weeks, p = 0.09). Lower levels of lactate dehydrogenase
      and gamma-glutamyltransferase, although always within the normal range, were
      found in patients with relapsing forms. CONCLUSION: COP is a specific but
      infrequent form of OP with a good response to steroid therapy. Relapses are
      frequent and typical characteristics of COP which resolved with ulterior
      treatment. Multifocal opacities on chest X-ray and a shorter maintenance of the
      initial steroid dose may increase the risk of relapse.

PMID- 17536185
TI  - Hemoptysis in a healthy young man after a stab wound to the chest.

PMID- 17536186
TI  - Immunotherapy against APP beta-secretase cleavage site improves cognitive
      function and reduces neuroinflammation in Tg2576 mice without a significant
      effect on brain abeta levels.
AB  - BACKGROUND/OBJECTIVES: Active and passive immunization methodologies against
      amyloid-beta (Abeta) are employed to clear and reduce cerebral Abetatowards
      treatment of Alzheimer's disease (AD) patients. The therapeutic potential of
      these antibodies in AD patients is limited because of adverse inflammatory
      reactions and cerebral hemorrhage, which are associated with the treatment. We
      propose a novel approach to inhibit Abeta production via antibodies against the
      beta-secretase cleavage site of the amyloid precursor protein (APP). Such an
      approach limits APP processing by beta-secretase, mainly through the endocytic
      pathway, and overcomes some of the limitations of BACE inhibition. Anti-APP beta
      site antibodies, tested in a cellular model expressing wild-type APP, were found
      to bind full-length APP, internalize into the cells and interfere with BACE
      activity, inhibiting both intra- and extracellular Abeta peptide formation.
      METHODS: We investigated the effect of anti-beta-site antibodies in an AD animal
      model regarding antibody efficacy, as well as possible adverse effects in the
      brain and periphery that may result from antibody treatment. RESULTS/CONCLUSIONS:
      Here, we show that long-term systemic administration of anti-APP beta-site
      antibodies to Tg2576 transgenic mice improved mouse cognitive functions
      associated with a reduction in both brain inflammation and the incidence of
      microhemorrhage. Furthermore, antibody treatment did not induce any peripheral
      autoimmunity responses. In spite of the beneficial effects observed in antibody
      treated mice, brain Abeta levels were not altered as a result of antibody
      treatment.

PMID- 17536187
TI  - Serum pro-hepcidin levels and relationship with ferritin in healthy non-anaemic
      infants.

PMID- 17536188
TI  - Antioxidant and antithrombus activities of enzyme-treated Salicornia herbacea
      extracts.
AB  - This study was attempted to investigate antioxidant and antithrombus activities
      of water and methanol extracts of enzyme-treated Salicornia herbacea (SH)by in
      vitro assays observing the inhibitory activity of a rat liver microsomal lipid
      peroxidation, DPPH radical scavenging activity, activated partial thromboplastin
      times (APTT) and thromboplastin times (TT). The water and methanol extracts from
      enzyme-treated SH inhibited the lipid peroxidation in a dose-dependent manner
      over a concentration range of 0.1-1.0 mg/ml. The activity of enzyme-treated water
      and methanol extracts was stronger than that of non-enzyme-treated water and
      methanol extracts. The inhibitory activity of the water extract was higher at a
      concentration of 1.0 mg/ml than that of the methanol extract. The activity was
      the highest in the enzyme-treated water extract, and was approximately 1.08 times
      higher than alpha-tocopherol, a natural antioxidant. The DPPH radical scavenging
      activities of the SH extracts were similar to their lipid peroxidation inhibitory
      activity. The APTT of the water and methanol extracts was delayed at a
      concentration range of 0.25-2.0 mg/ml in a dose-dependent manner. The APTT of the
      methanol extract was longer at a concentration of 1.0 mg/ml than that of the
      water extracts. The enzyme-treated methanol extract exhibited the longest APTT
      even at a concentration of 0.50 mg/ml. The TT activities of the SH extracts were
      also similar to their APTT activities. These results suggest that water and
      methanol extracts of the enzyme-treated SH may be useful as potential antioxidant
      and antithrombus sources, respectively.

PMID- 17536189
TI  - Conjugated linoleic acid reduces adipose depots without reduction of stearoyl
      coenzyme A desaturase 1 gene expression.
AB  - AIMS AND METHODS: This study investigated the effects of conjugated linoleic acid
      (CLA) on the body weight, fat deposition and the expression of stearoyl coenzyme
      A desaturase 1 (SCD1) in the livers of male ICR mice that were fed with either
      beef tallow (BT) or fish oil (FO) supplemented with CLA. Mice weighing 25-30 g
      were divided into four groups, BT and BT supplemented with 0.5% CLA (BTC), FO and
      FO supplemented with 0.5% CLA (FOC). Each group consisted of 8 mice, and they
      were fed the experimental diets for 4 weeks. The experimental diets were composed
      of 59.18% carbohydrates, 19.73% proteins and 21.09% fat in terms of their
      contributions to total calories, and other nutrients were identical. CLA was
      added to the diets of the CLA supplementation groups at 0.5% (w/w). The
      measurement of triglyceride (TG) was done by using a kit. Fatty acid compositions
      were analyzed in both the plasma and the liver using a gas chromatograph. The
      levels of SCD1 expression were analyzed by RT-PCR in the liver. RESULTS: No
      significant difference was found in the levels of food intake, body weight and
      food efficiency among experimental groups. However, the levels of both epididymal
      and visceral fat weight were significantly lower in the CLA-supplemented groups,
      BTC and FOC (p < 0.05). The level of the triglyceride concentration was also
      significantly lower in the CLA-supplemented groups (p < 0.05). The levels of the
      liver SCD1 gene expression were also higher in the CLA-supplemented groups.
      However, significant inhibition of conversion from C16:0 to C16:1 was found in
      both fatty acid compositions of the liver (p < 0.05). CONCLUSION: Addition of
      0.5% CLA did not inhibit the liver SCD1 gene expression; however, it showed
      decreasing effects on the fat pad weight, the concentration of TG and on fatty
      acid composition, leading to a decrease in the fat depositions. Such effects were
      clearer when CLA was supplemented to BT rather than FO.

PMID- 17536190
TI  - Decreased basal levels of glucagon-like peptide-1 after weight loss in obese
      subjects.
AB  - OBJECTIVE: Basal glucagon-like peptide-1 (GLP-1) concentrations seem to be
      attenuated in obese subjects, although statistical significance is unclear. Only
      a few studies have investigated the effect of weight reduction on GLP-1
      concentrations and have found unclear results. The aim of the present study was
      to determine whether subjects who lose weight on a hypocaloric diet experience
      the same change in circulating GLP-1 levels as subjects who do not lose weight.
      MATERIAL AND METHODS: A population of 99 obese nondiabetic outpatients was
      analyzed in a prospective way. Weight and blood pressure were determined. Basal
      glucose, C-reactive protein, insulin, total cholesterol, LDL cholesterol, HDL
      cholesterol, triglycerides, and basal GLP-1 blood levels were measured before and
      after 3 months of hypocaloric diet. Bipolar impedance examination was performed
      in all patients to assess body composition. The lifestyle modification program
      consisted of a hypocaloric diet (1,520 kcal, 52% carbohydrates, 25% lipids and
      23% proteins). The exercise program consisted of aerobic exercise for at least 3
      times per week (60 min each). RESULTS: Ninety-nine patients (20 male/79 female)
      gave informed consent and were enrolled in the study. Fourteen patients (2
      male/12 female) did not lose weight (group I: weight increase of 2 +/- 1.1 kg,
      NS) and 75 patients (18 male/67 female) lost weight (group II, weight loss of 4
      +/- 1.6 kg, p < 0.05). Weight, body mass index, fat mass, waist circumference,
      insulin, HOMA, LDL cholesterol, triglycerides and systolic blood pressure
      improved in group II, without significant statistical changes in group I. In
      group I, basal GLP-1 levels remained unchanged (7.4 +/- 3.1 vs. 7.15 +/- 3.6
      ng/ml, NS). In group II, GLP-1 levels decreased significantly (8.4%, 6.88 +/- 2.5
      vs. 6.3 +/- 2.4 ng/ml, p < 0.05). In the multivariate analysis with a dependent
      variable (levels of GLP-1 after hypocaloric diet adjusted by age and sex), only
      insulin levels remained as an independent predictor in the model (F = 5.9; p <
      0.05), with an increase of 0.6 ng/ml (CI 95%: 0.1-1.1) in GLP-1 concentrations
      with each 1-mIU/ml increase of insulin. CONCLUSION: Hypocaloric diet decreased
      GLP-1 levels in patients with weight loss with a significant improvement in
      anthropometric parameters and cardiovascular risk factors. Nevertheless, patients
      without weight loss after dietary treatment exhibited unchanged GLP-1 levels.
      Basal insulin correlates with basal GLP-1.

PMID- 17536191
TI  - Dairy products, calcium and the risk of breast cancer: results of the French
      SU.VI.MAX prospective study.
AB  - The aim was to estimate the association between dairy products (total and their
      subgroups), calcium intake and the risk of breast cancer. As few studies have
      considered menopausal status, we also investigated stratified analyses. This
      analysis included 3,627 women from the French SU.VI.MAX study, among whom 92
      developed breast cancer during the follow-up period. Food consumption was
      assessed based on five 24-hour records completed during the previous 18 months to
      follow-up. Calcium intake was calculated using an ad-hoc food composition
      database. Cox proportional hazards models were used to estimate relative risk
      (RR), comparing 4th quartile vs. 1st quartile, and 95% confidence intervals (95%
      CI). A lower risk of breast cancer was observed with high total dairy product
      consumption in the whole population (RR = 0.55, 95% CI = 0.29-1.03, p(trend) =
      0.03) and among premenopausal women with a RR of 0.35 (95% CI = 0.12-0.95,
      p(trend) = 0.01). None of these associations remained after control for calcium
      intake. Increasing calcium intake was inversely associated with breast cancer
      risk considering the whole population (RR = 0.50, 95% CI = 0.27-0.91, p(trend) =
      0.04) and among the subgroup of premenopausal women (RR = 0.26, 95% CI = 0.10
      0.71, p(trend) = 0.01) respectively. Our data support the hypothesis that dairy
      products, through calcium content or a correlated component, might have a
      negative association with the risk of breast cancer, particularly among
      premenopausal women.

PMID- 17536192
TI  - Self-reported dietary supplement use is confirmed by biological markers in the
      Norwegian Mother and Child Cohort Study (MoBa).
AB  - BACKGROUND/AIMS: A food frequency questionnaire (FFQ) and a database for dietary
      supplements were developed for use in the Norwegian Mother and Child Cohort Study
      (MoBa). The aim of the present study was to investigate the relation between
      reported use and biomarkers in supplement and non-supplement users and to
      validate self-reported intake of dietary supplements in mid pregnancy. METHOD:
      120 women were recruited from MoBa, and 119 subjects completed the MoBa FFQ and a
      4-day weighed food diary. Information on supplement use was collected by both
      methods. Venous blood specimens and 24-hour urine samples were obtained for
      measurement of dietary biomarkers. RESULTS: Biomarker concentration/excretion and
      intake differed significantly between supplement and non-supplement users for
      vitamin D, carotenoids, folate, the n-6/n-3 fatty acid ratio and iodine (p < 0.05
      for all variables). Flavonoid excretion was higher in flavonoid-supplement users
      (p < 0.05). Significant correlations between total dietary intake (food and
      supplements) and biomarker concentration/excretion were found for vitamin D (r =
      0.45, p < 0.001), folate (r = 0.26, p = 0.005), the n-6/n-3 fatty acid ratio (r =
      0.36, p < 0.001) and iodine (r = 0.42, p < 0.001). CONCLUSION: The biochemical
      indicators examined in this study confirmed differences in self-reported
      micronutrient intake between supplement and non-supplement users for vitamin D,
      beta-carotene, folate, n-3 fatty acids, flavonoids and iodine.

PMID- 17536193
TI  - Membrane fatty acids, oxidative burst and phagocytosis after enrichment of P388D1
      monocyte/macrophages with essential 18-carbon fatty acids.
AB  - The fatty acid composition of cell membranes can be modified in cell culture. The
      role of different fatty acid families in modulating phagocytosis and oxidative
      burst is not clear and therefore the influence of 18-carbon polyunsaturated fatty
      acids (PUFA) on these processes was examined. The mouse monocyte/macrophage line
      P388D1 was cultured in medium supplemented with 2 or 20 micromol/l 18:2n-6
      (linoleic acid; LA) or 18:3n-3 (alpha-linolenic acid; LNA) and fatty acid
      enrichment of the cells was tested after 8 days. The macrophages were activated
      with phorbol ester in order to promote oxidative burst and intracellular
      dihydrorhodamine oxidation was determined. To test phagocytosis capacity uptake
      of fluorescence-labeled Escherichia coli was determined. Activation of the
      transcription factor nuclear factor (NF)-kappaB was also determined. Cells grown
      in medium with 20 micromol/l LA contained 2- to 3-fold more n-6 PUFA including 4
      fold more arachidonic acid. Cells grown in medium with 20 micromol/l LNA
      contained 4-fold more n-3 PUFA. Both LA and LNA enhanced phagocytosis and
      decreased oxidative burst, with little difference between the fatty acids. NF
      kappaB activation at 1 h post-stimulation was not affected by adding LA or LNA to
      the culture medium. We conclude that the fatty acid composition of macrophages
      influences their ability to phagocytose and mount oxidative burst.

PMID- 17536194
TI  - Hormonal responses to a fast-food meal compared with nutritionally comparable
      meals of different composition.
AB  - BACKGROUND: Fast food is consumed in large quantities each day. Whether there are
      differences in the acute metabolic response to these meals as compared to
      'healthy' meals with similar composition is unknown. DESIGN: Three-way crossover.
      METHODS: Six overweight men were given a standard breakfast at 8:00 a.m. on each
      of 3 occasions, followed by 1 of 3 lunches at noon. The 3 lunches included: (1) a
      fast-food meal consisting of a burger, French fries and root beer sweetened with
      high fructose corn syrup; (2) an organic beef meal prepared with organic foods
      and a root beer containing sucrose, and (3) a turkey meal consisting of a turkey
      sandwich and granola made with organic foods and an organic orange juice.
      Glucose, insulin, free fatty acids, ghrelin, leptin, triglycerides, LDL
      cholesterol and HDL-cholesterol were measured at 30-min intervals over 6 h.
      Salivary cortisol was measured after lunch. RESULTS: Total fat, protein and
      energy content were similar in the 3 meals, but the fatty acid content differed.
      The fast-food meal had more myristic (C14:0), palmitic (C16:0), stearic (C18:0)
      and trans fatty acids (C18:1) than the other 2 meals. The pattern of nutrient and
      hormonal response was similar for a given subject to each of the 3 meals. The
      only statistically significant acute difference observed was a decrease in the
      AUC of LDL cholesterol after the organic beef meal relative to that for the other
      two meals. Other metabolic responses were not different. CONCLUSION: LDL
      cholesterol decreased more with the organic beef meal which had lesser amounts of
      saturated and trans fatty acids than in the fast-food beef meal.

PMID- 17536195
TI  - Iron intake in relation to diet and iron status of young adult women.
AB  - AIMS: To determine the iron intake and food sources of iron in young adult women
      and to compare women with high versus low iron intake on diet and iron status.
      METHODS: Iron intake and food sources were assessed by a 2-day estimated food
      record. Iron status was determined by a fasting venous blood sample. Differences
      in diet and iron status between women with high versus low iron intake were
      examined by comparing women of the fourth respectively first quartile of total
      iron intake (mg/day). RESULTS: The median total, heme and non-heme iron intake
      was 10.6, 0.6 and 9.8 mg/day, respectively. The median iron intake was 93 and
      131% of the estimated average requirement (EAR) of the UK (11.4 mg/day) and USA
      (8.1 mg/day), respectively. The most important iron intake contributors were
      cereals and cereal products (31%), meat and meat products (12%) and vegetables
      (10%). Women with a high iron intake showed a significantly higher energy
      adjusted intake of alcoholic beverages and soups and a lower intake of non
      alcoholic beverages than women with a low iron intake. Approximately 5% of the
      women had anemia, of which 3% had iron deficiency anemia (IDA). Almost 20% was
      iron-deficient non-anemic. In this regard, no significant differences were found
      between the iron intake quartiles. CONCLUSION: The median iron intake in this
      study population is considerably below the national recommended dietary allowance
      (20 mg/day). However, based on the approach of the Dietary Guidelines Advisory
      Committee, iron intake seems to pose no major health problem when using the EAR
      as a reference. The number of women with IDA was indeed not alarming (3%),
      although 20% was iron-deficient non-anemic. The question remains whether an
      increase in iron intake can improve iron status.

PMID- 17536196
TI  - Quantitative evaluation of new bone and fibrous tissue in the cochlea following
      cochlear implantation in the human.
AB  - The formation of new bone and fibrous tissue in the human inner ear following
      cochlear implantation was evaluated by computer-assisted 3-D reconstruction.
      Seven temporal bones from patients who in life had undergone cochlear
      implantation were prepared for histological study with the implant in situ. The
      specimens were sectioned in the axial plane at a thickness of 20 microm. At least
      every tenth section was digitally reconstructed in three dimensions and volumes
      of new bone and fibrous tissue were calculated per millimeter length of the
      cochlea. New bone and fibrous tissue were found in all seven specimens,
      particularly at the cochleostomy site. In addition, new bone and fibrous tissue
      had extended to variable lengths along the track of the cochlear implant and in
      some cases extended beyond the distal end of the implanted electrode. This
      methodology provides a quantitative tool for evaluation of new bone and fibrous
      tissue in the inner ear following implantation. This should assist in correlating
      psychophysical and speech perception tests with intracochlear pathology,
      evaluating both electrode design and the techniques of preserving residual
      auditory function.

PMID- 17536197
TI  - Aging effects on the activation of the auditory cortex during binaural speech
      listening in white noise: an fMRI study.
AB  - The functional significance of age-related pathology of the auditory cortex is
      not well established. The purpose of this study was to elucidate the activation
      pattern of the auditory cortex in aged subjects in response to speech signals.
      Functional magnetic resonance imaging was performed on 12 elderly subjects with
      normal hearing acuity during selective listening with both ears to speech sounds
      in quiet and in white noise. Twelve young, normal-hearing subjects served as
      controls. Our results showed that activation of the auditory cortex during
      selective listening to speech decreased in elderly subjects compared to young
      subjects, especially in noise. Reduced activation occurred in the anterior and
      posterior regions of the bilateral superior temporal gyrus (STG), but mainly in
      the posterior part of the left STG. In addition, background noise had a greater
      masking effect on speech perception in the elderly subjects than in the young
      ones. These findings suggest that early functional changes associated with
      central presbycusis occur mainly in the posterior part of the left STG.

PMID- 17536198
TI  - Spatial unmasking and binaural advantage for children with normal hearing, a
      cochlear implant and a hearing aid, and bilateral implants.
AB  - The aims of this study were to: (1) determine if spatial unmasking existed and
      differed for children with normal hearing, a hearing aid and a cochlear implant
      (CIHA), and bilateral implants (BICI); (2) determine if binaural advantage and
      headshadow effect differed between children with CIHA and BICI. Results indicated
      that most of the CIHA and BICI children demonstrated spatial unmasking, though to
      a lesser degree than children with normal hearing. Results also indicated that
      the children with BICI demonstrated greater headshadow effect than those with
      CIHA. The CIHA and BICI children also differed in binaural advantage, which could
      be due to the differences in headshadow effect and in detection abilities with
      the hearing aid versus the second implant.

PMID- 17536199
TI  - Effects of computer-assisted speech training on Mandarin-speaking hearing
      impaired children.
AB  - The present study investigated whether moderate amounts of computer-assisted
      speech training can improve the speech recognition performance of hearing
      impaired children. Ten Mandarin-speaking children (3 hearing aid users and 7
      cochlear implant users) participated in the study. Training was conducted at home
      using a personal computer for half an hour per day, 5 days per week, for a period
      of 10 weeks. Results showed significant improvements in subjects' vowel,
      consonant, and tone recognition performance after training. The improved
      performance was largely retained for 2 months after training was completed. These
      results suggest that moderate amounts of auditory training, using a computer
      based auditory rehabilitation tool with minimal supervision, can be effective in
      improving the speech performance of hearing-impaired children.

PMID- 17536200
TI  - Cochlear implant channel separation and its influence on speech perception-
      implications for a new electrode design.
AB  - There are a variety of factors which can influence cochlear implantation outcome.
      Channel interaction is one of the variables responsible for audiological
      performance deterioration in multichannel implants. Electrode design is--among
      others--one way to decrease the incidence of channel interaction. At present,
      electrodes differ in overall length, diameter, contact design and distribution,
      but none of the electrodes available have a distinct variability in the amount of
      space between contacts across the length of the electrode. The aim of this study
      was to investigate whether a new electrode design featuring larger contact
      spacing in the apical part of deeply inserted electrodes would lead to an
      increase in speech perception. Eighteen postlingually deafened patients fitted
      with MedEl Combi 40+ or MedEl Pulsar cochlear implants using the MedEl
      implementation of continuous interleaved sampling participated in this study.
      Patients were tested in 6 conditions, in which the channel spacing and
      distribution of electrode contacts in each patient were artificially varied by
      activating or deactivating different channels. Performance was tested immediately
      after each change in setup with a monosyllable and sentence test (Hochmaier,
      Schultz and Moser). Our results showed that the condition with the highest
      distance between contacts in the apical part (up to 6.4 mm instead of 2.4 mm) is
      the most effective for the matched map condition: the results improved
      statistically significantly for the sentence test from 72% in the standard 12
      channel condition to 83.2% and from 40.8 to 50% for the monosyllable test. Based
      on these findings, we present a new electrode design which can help achieve
      further increases in speech perception with cochlear implants.

PMID- 17536201
TI  - Transient deafness in young candidates for cochlear implants.
AB  - This study describes 5 infants who were diagnosed with auditory neuropathy (AN)
      associated with severe to profound neural hearing loss shortly after birth.
      However, on repetition of the tests 7-12 months later, all infants showed full or
      partial recovery. The follow-up electrophysiological patterns were characterized
      by the appearance of wave I, followed by wave III and V, reflecting
      synchronization of auditory pathways and improvement in auditory nerve function.
      Suspected causative or contributory factors were neonatal hyperbilirubinemia,
      hypoxia, ischemia, and central nervous system immaturity, alone or in
      combination. These findings indicate that lack of an auditory brain stem response
      does not necessarily mean no hearing and that the situation where AN exists can
      improve. Thus, clinicians should be made aware that although cochlear implants
      may yield better auditory performance when applied early, they should be
      considered a therapeutic option only after repeated measures have proved
      persistent AN, and no child should be considered for an implant until a
      behavioral measure of hearing has been obtained.

PMID- 17536202
TI  - Treatment of epileptogenic cavernomas: surgery versus radiosurgery.
AB  - BACKGROUND: Epilepsy is the most common symptom of cavernoma. Although
      microsurgery is the mainstay treatment for epileptogenic cavernoma, this
      procedure may cause severe complications for some lesions. This report aimed to
      study if linear accelerator (LINAC) radiosurgery was an alternative treatment
      modality for epileptogenic cavernoma. METHODS: In this retrospective study, 29
      patients were diagnosed with epileptogenic cavernomas from September 1995 to
      March 2005. Fifteen patients were treated with surgical excision and 14 with
      LINAC radiosurgery. The evaluation of epilepsy control was according to Engel's
      classification. RESULTS: In the surgical group, 13 (86.7%) of 15 patients had a
      class I seizure-free outcome. In the radiosurgery group, class I control was
      achieved in 9 (64.3%) of 14 patients. However, there was no significant
      difference in the results of treatment between the two groups. CONCLUSIONS: LINAC
      radiosurgery is an alternative treatment for epileptogenic cavernomas, especially
      when the lesions are located in the central regions or eloquent areas of the
      brain.

PMID- 17536204
TI  - Capecitabine-induced headache responding to diltiazem.
AB  - BACKGROUND: Headaches have been reported as a potential side effect of
      capecitabine therapy. However, severe limiting headaches are rarely experienced
      in this setting and no known therapy has been described for such a serious side
      effect. RESULTS: We report the case of a patient treated with capecitabine and
      radiation for rectal adenocarcinoma. The patient developed grade 3 capecitabine
      induced headache. A cause-effect relationship to capecitabine was suggested due
      to resolution of headache with capecitabine withdrawal and reappearance with
      capecitabine rechallenge. The patient's headache resolved with diltiazem therapy
      and she was able to complete capecitabine and radiation therapy without further
      adverse events. CONCLUSIONS: Capecitabine and 5-fluorouracil (5-FU) are known
      vasospasm inducers. We hypothesize that capecitabine-induced headache is vascular
      in nature. This likely explains the noted response to a calcium channel blocker
      (CCB), namely diltiazem. CCBs should be considered in the treatment of 5-FU or
      capecitabine-induced headaches.

PMID- 17536205
TI  - Surgical Symposia during the 14th UEGW, Berlin, Germany, 2006.

PMID- 17536206
TI  - Predictors of cessation of regular leisure-time physical activity in community
      dwelling elderly people.
AB  - BACKGROUND: Maintaining regular physical activity is important for physical and
      mental health, providing benefits including protection against chronic disease.
      However, little is known about the causes of cessation of habitual physical
      activity in older people. OBJECTIVES: To identify predictors of cessation of
      regular physical activity in community-dwelling elderly people. METHODS: 582
      community-dwelling people aged 70 years and over who were living in Tokyo, Japan,
      were surveyed regarding physical activity levels 2 years after completing an
      initial survey where they indicated they took part in physical activity at least
      5 days a week. Baseline demographic, health, physical functioning and
      psychological status measures were used as predictors of exercise cessation.
      RESULTS: At the 2-year follow-up, 192 subjects (33%) had ceased taking part in
      regular physical activity. In univariate analyses, women, smokers, those who
      reported a fear of falling and those with a slower walking speed at baseline were
      significantly more likely to cease regular physical activity. Multiple logistic
      regression analysis identified 3 of these variables as significant and
      independent predictors of activity cessation: female gender (adjusted OR = 1.67,
      95% CI = 1.13-2.47); smoking (OR = 2.34, 95% CI = 1.33-4.13), and slow walking
      speed (OR = 1.79, 95% CI = 1.07-2.98). CONCLUSIONS: The study identified simple
      screening measures for identifying elderly people at risk of ceasing regular
      physical activity. Currently active older people with these factors may benefit
      from counseling and interventions to enable them to continue participating in
      regular physical activity.

PMID- 17536207
TI  - Preventing falls in physically active community-dwelling older people: a
      comparison of two intervention techniques.
AB  - BACKGROUND: Falls are common in physically active older people; however, most
      intervention studies have been targeted at frail older people. OBJECTIVE: To
      evaluate the effectiveness of two intervention techniques for preventing falls in
      physically active community-dwelling older people. METHODS: Two hundred and
      seventeen people (120 men and 97 women) aged between 70 and 90 years recruited
      from a health insurance company membership database were randomly allocated to
      receive either a psychomotor intervention focusing on body awareness, body
      experience and coordination, a fitness intervention focusing on functional
      skills, strength, endurance and flexibility, or no intervention (control group).
      The outcome measures were prospective falls (number of fallers, number of
      multiple fallers, number of falls and falls rate) and measures of physical
      performance (Timed Up and Go Test, maximal step length, sit-to-stand time, normal
      and fast walking speed). RESULTS: At the 4-month follow-up, significant
      improvements in the Timed Up and Go Test and sit-to-stand times were observed for
      both the psychomotor and fitness intervention groups. During the 12-month follow
      up period, 39% of the participants fell at least once, and 19% fell on multiple
      occasions. The proportion of fallers in the fitness intervention group was 23%
      less than in the control group (RR = 0.77, 95% CI 0.60-0.97), but no significant
      reduction in falls was observed in the psychomotor intervention group.
      CONCLUSION: A fitness training program improves some aspects of physical
      performance and reduces falls by 23% in physically active older people.

PMID- 17536208
TI  - Concomitant lower serum albumin and vitamin D levels are associated with
      decreased objective physical performance among Japanese community-dwelling
      elderly.
AB  - BACKGROUND: Previous studies have shown that serum albumin or vitamin D is
      associated with physical performance. We hypothesized that older adults with
      concomitant lower serum albumin and vitamin D (25-hydroxyvitamin D, 25OHD) levels
      are associated with decreased physical performance compared to those with 1 or
      none of the 2 risk factors. OBJECTIVE: To investigate the association of combined
      serum albumin and 25OHD levels with physical performance (muscle strength and
      balance capability) in community-dwelling elderly. METHODS: A cross-sectional
      study in a community-based population in the province of Tokyo, Japan, was
      performed. For the study, 1,094 community-dwelling people aged 70 and older
      underwent an interview, anthropometric measurements, blood analysis and physical
      performance testing. The subjects were classified into 4 types by combining serum
      albumin and 25OHD levels: lower albumin only, lower vitamin D only, lower albumin
      and lower vitamin D, higher albumin and higher vitamin D. RESULTS: Men with
      concomitant lower albumin and lower 25OHD levels had significantly decreased knee
      extension power, usual timed Up & Go and maximal timed Up & Go, even after
      adjusting for age and body mass index (BMI). In women, concomitant lower albumin
      and lower vitamin D was associated with significantly decreased handgrip strength
      and functional reach, even after adjusting for age and BMI. Subjects with
      combined lower albumin and lower vitamin D levels showed a significant decline in
      muscle strength and balance capability compared to higher albumin and higher
      vitamin D, even after adjusting for age, current drinking or smoking status,
      physical activity, history of chronic disease, basic activities of daily living,
      instrumental activities of daily living, BMI and bone mineral density.
      CONCLUSION: Concomitant lower serum albumin and lower vitamin D levels are
      associated with decreased muscle strength and balance capability in both men and
      women. These results suggest that serum albumin and 25OHD together may be an
      important target for strategies aiming to achieve a healthy life and prevent loss
      of independence in community-dwelling elderly.

PMID- 17536209
TI  - A unified approach for quantifying, testing and correcting population
      stratification in case-control association studies.
AB  - The HapMap project has given case-control association studies a unique
      opportunity to uncover the genetic basis of complex diseases. However, persistent
      issues in such studies remain the proper quantification of, testing for, and
      correction for population stratification (PS). In this paper, we present the
      first unified paradigm that addresses all three fundamental issues within one
      statistical framework. Our unified approach makes use of an omnibus quantity
      (delta), which can be estimated in a case-control study from suitable null loci.
      We show how this estimated value can be used to quantify PS, to statistically
      test for PS, and to correct for PS, all in the context of case-control studies.
      Moreover, we provide guidelines for interpreting values of delta in association
      studies (e.g., at alpha = 0.05, a delta of size 0.416 is small, a delta of size
      0.653 is medium, and a delta of size 1.115 is large). A novel feature of our
      testing procedure is its ability to test for either strictly any PS or only
      'practically important' PS. We also performed simulations to compare our
      correction procedure with Genomic Control (GC). Our results show that, unlike GC,
      it maintains good Type I error rates and power across all levels of PS.

PMID- 17536210
TI  - Pre- and post-Columbian gene and cultural continuity: the case of the Gaucho from
      southern Brazil.
AB  - OBJECTIVE: To investigate the evolutionary and demographic history of the Gaucho,
      a distinct population of southern Brazil, relating it to their culture, to assess
      possible parallel continuity. METHODS: Six binary polymorphisms, an Alu insertion
      polymorphism (YAP) and 12 short tandem repeat loci in the non-recombining region
      of the Y-chromosome, as well as the sequence of the first hypervariable segment
      (HVS-I) of the mitochondrial DNA (mtDNA) control region were studied in 150
      unrelated males born in the Pampa region of Rio Grande do Sul. RESULTS:
      Comparison of the results with the other Brazilian and Uruguayan populations, as
      well as with their putative ancestors, indicated a stronger male Spanish
      influence than that observed elsewhere in Brazil, a former Portuguese colony.
      Extensive mtDNA analyses of their Amerindian component gave clear indications of
      the presence there of material from extinct (Charrua), as well as extant
      (Guarani) tribes. CONCLUSIONS: The genetic analyses contributed in a significant
      way to reveal that the known cultural continuity between pre- and post-Columbian
      Pampa populations was also accompanied by an extraordinary genetic continuity.

PMID- 17536211
TI  - Incorporating genotyping uncertainty in haplotype frequency estimation in
      pedigree studies.
AB  - AIMS: Haplotype frequency estimation is indispensable in studies of human
      genetics based on haplotypes since studies based on haplotypes are likely to
      yield more information than those based on single SNP marker. However, most
      existing algorithms estimate haplotype frequencies under the assumption that all
      of the genotype data sets are correct. To date, nearly all large genotype data
      sets have errors, and studies have demonstrated that even a small quantity of
      genotyping errors can have enormous impact on haplotype frequency estimation.
      METHODS: Although the GenoSpectrum (GS)-EM algorithm which estimates haplotype
      frequencies incorporating genotyping uncertainty has been presented recently [1],
      it can only be suitable for independent individuals rather than dependent
      pedigree data. In this paper, we describe a new EM algorithm, called GS-PEM, that
      calculates maximum likelihood estimates (MLEs) of haplotype frequencies based on
      all possible multilocus genotypes (GenoSpectrum) of each member of the pedigrees
      through making use of the dependence information of relatives. RESULTS AND
      CONCLUSION: We evaluate the performance of the GS-PEM by simulation studies and
      find that our GS-PEM can reduce the impact induced by the genotyping errors in
      haplotype frequency estimation.

PMID- 17536212
TI  - A ridge penalized principal-components approach based on heritability for high
      dimensional data.
AB  - OBJECTIVE: To develop a ridge penalized principal-components approach based on
      heritability that can be applied to high-dimensional family data. METHODS: The
      first principal component of heritability for a trait constellation is defined as
      a linear combination of traits that maximizes the heritability, which is
      equivalent to maximize the family-specific variation relative to the subject
      specific variation. To analyze high-dimensional data and prevent overfitting, we
      propose a penalized principal-components approach based on heritability by adding
      a ridge penalty to the subject-specific variation. We choose the optimal
      regularization parameter by cross-validation. RESULTS: The principal-components
      approach based on heritability with and without ridge penalty was compared to the
      usual principal-components analysis in four settings. The penalized principal
      components of heritability analysis had substantially larger coefficients for the
      traits with genetic effect than for the traits with no genetic effect, while the
      non-regularized analysis failed to identify the genetic traits. In addition,
      linkage analysis on the combined traits showed that the power of the proposed
      methods was higher than the usual principal-components analysis and the non
      regularized principal-components of heritability analysis. CONCLUSIONS: The
      penalized principal-components approach based on heritability can effectively
      handle large number of traits with family structure and provide power gain for
      linkage analysis. The cross-validation procedure performs well in choosing
      optimal magnitude of penalty.

PMID- 17536213
TI  - MOD-score analysis with simple pedigrees: an overview of likelihood-based linkage
      methods.
AB  - A MOD-score analysis, in which the parametric LOD score is maximized with respect
      to the trait-model parameters, can be a powerful method for the mapping of
      complex traits. With affected sib pairs, it has been shown before that MOD scores
      asymptotically follow a mixture of chi(2) distributions with 2, 1 and 0 degrees
      of freedom under the null hypothesis of no linkage. In that context, a MOD-score
      analysis yields some (albeit limited) information regarding the trait-model
      parameters, and there is a chance for an increased power compared to a simple LOD
      score analysis. Here, it is shown that with unilineal affected relative pairs,
      MOD scores asymptotically follow a mixture of chi(2) distributions with 1 and 0
      degrees of freedom under the null hypothesis, that is, the same distribution as
      followed by simple LOD scores. No information regarding the trait model can be
      obtained in this setting, and no power is gained when compared to a LOD-score
      analysis. An outlook to larger pedigrees is given. The number of degrees of
      freedom underlying the null distribution of MOD scores, that depends on the type
      of pedigrees studied, corresponds to the number of explored dimensions related to
      power and to the number of parameters that can jointly be estimated.

PMID- 17536214
TI  - Administration of anti-IgE to a Churg-Strauss syndrome patient.
AB  - BACKGROUND: Treatment of the Churg-Strauss syndrome (CCS) remains a challenge.
      Many patients relapse after achieving remission, and a substantial proportion of
      them present adverse drug reactions with relevant morbidity. In most patients,
      severe asthma and upper respiratory symptoms persist, requiring continuous
      therapy. The aim of the present study is to describe a patient with CSS who was
      administered anti-IgE. CASE REPORT: A 46-year-old male patient with CSS followed
      up for 17 years is described. Upon treatment, CSS showed remission but asthma
      failed to improve despite high-dose inhaled corticosteroids, long-acting beta2
      agonists and several courses of systemic steroids. In order to better control
      asthma, anti-IgE was administered. Following omalizumab administration, asthma
      symptoms (according to clinical features and lung function tests) and
      eosinophilia improved. CONCLUSIONS: Anti-IgE offers the potential not only to
      decrease asthma activity but also to reduce the risk of morbidity that can result
      from currently available treatment options. Whether it can also affect the
      activity of other CSS components is an open question. As far as we know, there
      are no published reports about the prescription of omalizumab to patients with
      CSS and with non-allergic asthma. Anti-IgE improved our patient's asthma and
      decreased the eosinophil blood count but did not worsen the outcome of CSS.
      However, large and long-term studies are necessary before a more widespread
      utilization of anti-IgE in CSS patients can be implemented.

PMID- 17536215
TI  - Chronic rhinitis with nasal polyposis associated with sodium glutamate
      intolerance.
AB  - The study reports a case of perennial rhinitis with bilateral polyposis. A
      careful diagnostic workup revealed that the disorder was caused by sodium
      glutamate intolerance. This is the first study showing an association between
      intolerance to food additives and nasal polyposis.

PMID- 17536216
TI  - Links between pollen, atopy and the asthma epidemic.
AB  - Pollen allergy has been found in 80-90% of childhood asthmatics and 40-50% of
      adult-onset asthmatics. Despite the high prevalence of atopy in asthmatics, a
      causal relationship between the allergic response and asthma has not been clearly
      established. Pollen grains are too large to penetrate the small airways where
      asthma occurs. Yet pollen cytoplasmic fragments are respirable and are likely
      correlated with the asthmatic response in allergic asthmatics. In this review, we
      outline the mechanism of pollen fragmentation and possible pathophysiology of
      pollen fragment-induced asthma. Pollen grains rupture within the male flowers and
      emit cytoplasmic debris when winds or other disturbances disperse the pollen.
      Peak levels of grass and birch pollen allergens in the atmosphere correlated with
      the occurrence of moist weather conditions during the flowering period.
      Thunderstorm asthma epidemics may be triggered by grass pollen rupture in the
      atmosphere and the entrainment of respirable-sized particles in the outflows of
      air masses at ground level. Pollen contains nicotinamide adenine dinucleotide
      phosphate (reduced) oxidases and bioactive lipid mediators which likely
      contribute to the inflammatory response. Several studies have examined
      synergistic effects and enhanced immune response from interaction in the
      atmosphere, or from co-deposition in the airways, of pollen allergens, endogenous
      pro-inflammatory agents, and the particulate and gaseous fraction of combustion
      products. Pollen and fungal fragments also contain compounds that can suppress
      reactive oxidants and quench free radicals. It is important to know more about
      how these substances interact to potentially enhance, or even ameliorate,
      allergic asthma.

PMID- 17536217
TI  - Dietary pulverized konjac glucomannan suppresses scratching behavior and skin
      inflammatory immune responses in NC/Nga mice.
AB  - BACKGROUND: Feeding with pulverized konjac glucomannan (PKGM) suppresses the
      development of eczema and hyper-IgE production in NC/Nga mice, a model of atopic
      dermatitis. This study aimed to examine the effects of PKGM on scratching
      behavior and skin inflammatory immune responses in NC/Nga mice. METHODS: Four
      week-old NC/Nga mice were maintained for 8 or 9 weeks on diet containing PKGM.
      Scratching behavior and clinical symptoms were evaluated every 2 weeks. Effects
      of PKGM on cutaneous inflammation were evaluated by histopathological analysis.
      Local expression levels of substance P and proinflammatory cytokines were
      measured by ELISA. RESULTS: An increase in scratching behavior was evident from 6
      weeks of age in control mice, but this symptom was dose-dependently inhibited in
      PKGM-fed mice. Continuous PKGM feeding then significantly inhibited eczematous
      skin lesions including hyperkeratosis, dermal mastocytosis and eosinophilia.
      Concomitantly, cutaneous overproductions of substance P, IL-10, IL-4, and TNF
      alpha were all suppressed in PKGM-fed mice. CONCLUSIONS: PKGM feeding markedly
      suppressed development of scratching behavior, substance P expression with
      mastocytosis, and skin inflammatory immune responses in NC/Nga mice.

PMID- 17536218
TI  - A NOS1 gene polymorphism associated with asthma and specific immunoglobulin E
      response to mite allergens in a Colombian population.
AB  - BACKGROUND: Nitric oxide (NO) is involved in asthma pathogenesis and is
      synthesized by three isoforms of NO synthase, one of them encoded by NOS1 gene.
      The CA-repeat and the C5266T SNP in NOS1 exon 29 have been associated with asthma
      and IgE levels. We thought to test the association of asthma and asthma-related
      phenotypes with the exon 29 CA-repeat and the C5266T SNP in a Colombian
      population sample. METHODS: The CA-repeat and the C5266T SNP were genotyped in
      167 asthmatics and 166 controls using PCR-based fragment length polymorphism and
      TaqMan assay. We also determined total and mite-specific IgE against Blomia
      tropicalis and Dermatophagoides pteronyssinus. RESULTS: Three new CA-repeat
      alleles, 14, 23 and 24 repeats were detected. Allele comprising 16 repeats was
      associated with asthma (OR: 1.90 (CI 1.22-2.97, p(c) = 0.028) and low total (p(c)
      = 0.02) and specific IgE to B. tropicalis (p(c) < 0.0001) and D. pteronyssinus
      (p(c) < 0.0001). We found no association of the C5266T SNP and asthma or IgE
      levels. CONCLUSION: NOS1 exon 29 CA-repeat may be a risk factor for asthma
      susceptibility and mite specific IgE response in a Colombian population.

PMID- 17536219
TI  - Polymorphisms in the IL-4, IL-4 receptor alpha chain, TNF-alpha, and lymphotoxin
      alpha genes and risk of asthma in Hong Kong Chinese adults.
AB  - BACKGROUND: Susceptibility to the development of asthma and other atopic diseases
      is known to be associated with genetic components. However, association studies
      with interleukin-4 (IL-4), IL-4 receptor alpha subunit (IL-4R alpha), tumor
      necrosis factor-alpha (TNF-alpha) and lymphotoxin-alpha (LT-alpha) genes were
      inconclusive, as both positive and negative results were obtained in several
      populations studied. We aimed to investigate the association of the polymorphisms
      for IL-4 (C-589T), IL-4R alpha (Gln576Arg), TNF-alpha (G-308A) and LT-alpha
      (A252G) genes as candidates and asthma in adult Hong Kong Chinese population.
      METHODS: The association study was conducted in an age- and smoking status
      matched case-control design in asthma patients (n = 292) and healthy controls (n
      = 292) using polymerase chain reaction and restriction fragment length
      polymorphism. RESULTS: No significant differences were found in allele and
      genotype frequencies of all four genes between patients and controls. After
      stratification by atopic status, the heterozygous AG genotype of LT-alpha (A252G)
      was found to increase risk of asthma in atopic population [odds ratio (OR) =
      2.00, 95% CI 1.09-3.67, p = 0.024]. When stratified by smoking status, we found
      increased risk of asthma with subjects carrying the heterozygous AG and
      homozygous GG genotypes of LT-alpha in ever-smokers (OR = 2.73, 95% CI 1.11-6.69,
      p = 0.028 for heterozygotes; OR = 3.34, 95% CI 1.16-9.62, p = 0.026 for
      homozygotes). CONCLUSION: Our results suggest that the variability of LT-alpha
      genotypes may have potential implications for individual susceptibility to asthma
      in atopic or in ever-smoking Chinese adults in Hong Kong.

PMID- 17536220
TI  - Changes in plasma TARC levels during Japanese cedar pollen season and
      relationships with symptom development.
AB  - BACKGROUND: Japanese cedar pollinosis (JCPsis) is an immunoglobulin E-mediated
      type I allergy caused by exposure to Japanese cedar pollen (JCP). Blood thymus
      and activation-regulated chemokine (TARC) levels are well known as an objective
      parameter for disease severity for several allergic disorders. The present study
      aims to evaluate the relationship between TARC levels and disease symptoms during
      the pollen season. METHODS: Analysis was performed of results of symptom scores
      and blood parameters obtained from 42 JCPsis patients who participated in a
      probiotic (Bifidobacterium longum BB536) intake trial in the JCP season of 2005
      (January to April), using a randomized, double-blind, placebo-controlled design.
      RESULTS: Significant increases in plasma TARC levels were observed in subjects
      receiving placebo (p < 0.05 in February and p < 0.01 in March), but not in
      subjects receiving BB536. Increased plasma TARC levels were markedly greater in
      subjects who experienced severe symptoms and were thus excluded early from the
      intervention (placebo group: n = 8; BB536 group: n = 2). Significant differences
      were found in changes from baseline TARC levels in February and March between the
      subjects where treatment was terminated early and the remaining ones. Among the
      remaining subjects, significant positive correlations were found as regards
      changed values of TARC compared to baseline in March and April with symptom
      scores recorded in the pollen season. CONCLUSION: Changed values of blood TARC in
      the pollen season may offer promising parameters for assessing disease severity
      and monitoring treatment.

PMID- 17536221
TI  - Hospitalizations for anaphylaxis in Florida: epidemiologic analysis of a
      population-based dataset.
AB  - BACKGROUND: Previous epidemiologic studies of anaphylaxis have been single
      institution investigations. The objective of this study was to determine the
      annual hospital discharge rate and risk factors for anaphylaxis outcomes
      throughout Florida. METHODS: 464 patients who were hospitalized in Florida for
      anaphylaxis and discharged in 2001 were identified using a statewide database and
      ICD-9-CM (International Classification of Diseases, 9th revision, Clinical
      Modification) codes. Linear regression was used to determine the predictors of
      length of stay (LOS) and total charges. Relative risks (RR) for ventilator
      assisted respiration and anaphylaxis due to food were calculated using binomial
      regression. RESULTS: Annual hospital discharge rate for anaphylaxis was
      2.8/100,000 population. Hospital mortality rate was 0.86%. Median LOS was 1 day.
      Median total charges was USD 4,982. Asthmatics had increased risk of receiving
      ventilator-assisted respiration (adjusted RR = 2.72, p = 0.04). Likelihood of
      hospitalization for anaphylaxis increased with age for both sexes (p < 0.0001).
      Patients who were <18 years old were three times as likely to be hospitalized for
      food anaphylaxis (versus other causes) compared to patients who were 71+ years
      old (adjusted RR = 3.25, p = 0.004). CONCLUSION: Young age was associated with
      increased risk of hospitalization for anaphylaxis to foods. Asthmatics had
      increased risk of receiving ventilator-assisted respiration. Likelihood of
      hospitalization increased with age.

PMID- 17536222
TI  - Premedication with montelukast reduces local reactions of allergen immunotherapy.
AB  - BACKGROUND: Local reactions (LRs) are a very frequent side effect of specific
      immunotherapy with allergens and can impair patients' adherence. Antihistamine
      pretreatment--originally introduced as a safety measure to reduce anaphylactic
      side effects--has been the only treatment option for LRs so far, although these
      swellings usually do not appear immediately but after hours. We were interested
      whether pretreatment with the leukotriene antagonist montelukast would be better
      suited for preventing those reactions than pretreatment with the antihistamine
      desloratadine. METHODS: Fifteen patients with a history of severe anaphylactic
      reactions to hymenoptera stings were enrolled into a prospective, double-blind,
      randomized, placebo-controlled pilot study. We selected a rush immunotherapy
      protocol consisting of 19 injections of hymenoptera venom administered over 5
      consecutive days, where the majority is developing LRs, and counted the number of
      injections until an LR of >3 cm occurred. The patients were randomized to 3
      treatment groups: premedication with placebo, 10 mg montelukast and 5 mg of the
      antihistamine desloratadine. RESULTS: Compared with placebo, the occurrence of
      LRs (>3 cm) was significantly delayed by montelukast (p < 0.01, analysis of
      variance) but not by desloratadine (p = 0.19). The difference between montelukast
      and desloratadine was close to significant (p = 0.054). Itching, recorded on a
      scale from 0 to 5, did not differ between the 3 groups. CONCLUSION: Montelukast
      can be useful in the prevention of LRs after specific immunotherapy.

PMID- 17536223
TI  - Risk factors for allergy due to the two-spotted spider mite (Tetranychus urticae)
      among table grape farm workers.
AB  - BACKGROUND: Recent studies have reported an increased prevalence of respiratory
      symptoms among farm workers. The aim of this study was to identify risk factors
      associated with spider mite allergy among table grape farm workers. METHODS: A
      cross-sectional study of 207 workers in table grape farms was conducted. Skin
      prick tests used extracts of 8 common aeroallergens, grape mould (Botrytis
      cinerea) and Tetranychus urticae. Specific IgE to T. urticae was quantified using
      ImmunoCAP (Phadia). Erythrocyte cholinesterase levels were determined using the
      Test-mate ChE Cholinesterase Test System (model 460). RESULTS: The average
      duration of employment of workers was 10 years and 12% were pesticide crop
      sprayers. Work-related wheeze (26%), ocular-nasal (24%) and urticaria/skin
      symptoms (14%) were more prevalent in the orchards. The prevalence of
      sensitization (skin prick test) was highest to T. urticae (22%) followed by house
      dust mite (16%), with 25% being atopic. The prevalence of allergy to T. urticae
      (skin reactivity and work-related symptoms) was 9.5%, with respiratory allergy
      (6%) more common than skin allergy (3%). Work-related ocular-nasal (OR = 4.9) and
      skin (OR = 3.7) symptoms were more commonly reported by pesticide crop sprayers.
      Workers with T. urticae-allergic rhino-conjunctivitis and probable asthma were
      more likely to be atopic, spray pesticides and have low (<30 U/g hemoglobin)
      erythrocyte cholinesterase levels. CONCLUSIONS: This study demonstrated that
      spider mite, T. urticae, is an important outdoor allergen among table grape farm
      workers. The increased risk of spider mite allergy appears to be related to high
      pesticide exposure among crop sprayers.

PMID- 17536224
TI  - Anaphylaxis to gadobenate dimeglumine (Multihance): a case report.
AB  - BACKGROUND: Gadolinium chelates are relatively safe contrast media used in MRI.
      Immediate severe adverse effects are exceptionally rare and mostly concern mild
      anaphylactoid reactions. We report a case of anaphylaxis to gadobenate
      dimeglumine (Gd-BOPTA, Multihance), a gadolinium-based contrast agent. METHODS: A
      32-year-old female patient with a personal history of multiple sclerosis, while
      undergoing an MRI scan, developed bronchospasm and acute urticaria with diffuse
      giant pruritic plaques in the first minute of Gd-BOPTA infusion. The procedure
      was cancelled and acute treatment of the reaction took place. The patient
      reported 2 additional MRI scans with definite use of unknown contrast media in
      the past 2 years without any adverse effect. Blood samples were obtained 2 and 48
      h after the reaction for measurement of serum tryptase concentration (Pharmacia
      Diagnostics, Uppsala, Sweden). Skin prick tests and intradermal tests were
      performed using 1:1,000, 1:100 and 1:10 dilution of the offending agent and
      alternative gadolinium-based agents [gadodiamide (Omniscan) and gadoteric acid
      (Dotarem)]. A group of 10 nonatopic individuals who underwent the same skin
      testing comprised the control group. RESULTS: Tryptase concentration was highly
      elevated 2 h after the reaction (21 microg/l) compared with that at 48 h (3
      microg/l). Skin prick tests in our patient were all negative, while intradermal
      testing with 0.03 ml of 1:100 and 1:10 preparations of Multihance showed a
      definite positive wheal-and-flare reaction. Skin tests to the alternative agents
      showed no response. In the control group, all performed tests were negative.
      CONCLUSION: We report the first case of an allergic reaction to gadobenate
      dimeglumine. Besides, skin testing seems to be a precious diagnostic tool which,
      if positive, strongly suggests a mast cell-mediated underlying mechanism.

PMID- 17536225
TI  - Circadian blood pressure variation and antihypertensive medication adjustment in
      normoalbuminuric type 2 diabetes patients.
AB  - BACKGROUND/AIMS: The aim of the study was to assess the effect of an
      antihypertensive treatment adjustment on 24-hour blood pressure variation in type
      2 diabetes patients. METHODS: The study group included 59 hypertensive type 2
      diabetes patients subjected to a single one-step antihypertensive agent dose
      adjustment (increase or decrease). Ambulatory blood pressure monitoring was
      performed at baseline and 4-6 weeks after the treatment modification. Controls
      were 41 matched patients, in whom antihypertensive treatment remained unchanged.
      RESULTS: At baseline, 45 (76%) study group patients and 29 (71%) controls were
      'non-dippers'; a similar number of patients in both groups converted to 'dipping'
      or vice versa: 11 (19%) from the study group and 7 (17%) controls. 'Converters'
      from the study group were significantly younger (47.5 +/- 3.9 vs. 56.4 +/- 12.2
      years; p < 0.05) and had lower 24-hour systolic blood pressure than 'non
      converters': 113.7 +/- 7.2 vs. 127.7 +/- 20.3 mm Hg (p < 0.01). CONCLUSION: A
      single one-step antihypertensive medication adjustment does not affect 'dipping'
      status in type 2 diabetes patients. However, the assessment of blood pressure
      variation should be made with greater caution in younger type 2 diabetes subjects
      with low systolic blood pressure.

PMID- 17536226
TI  - Indapamide decreases plasma adiponectin concentration in patients with essential
      hypertension.
AB  - BACKGROUND/AIM: Adiponectin is an adipose tissue-specific protein with
      antiatherogenic and insulin-sensitizing properties. In patients with essential
      hypertension, plasma adiponectin concentrations are lower than in healthy
      subjects. Antihypertensive drugs do not uniformly influence components of the
      metabolic syndrome. Therefore, the aim of this study was to evaluate the
      influence of 6 months' monotherapy with different antihypertensive drugs on
      plasma adiponectin concentration in essential hypertension patients. METHODS:
      Forty essential hypertension patients were randomized to receive enalapril,
      metoprolol, amlodipine or indapamide. Plasma concentrations of adiponectin,
      insulin, glucose and body fat content were estimated twice: before and after 6
      months of antihypertensive monotherapy. RESULTS: Plasma adiponectin concentration
      did not change significantly after enalapril (11.5 +/- 4.8 vs. 11.1 +/- 4.1
      mg/l), metoprolol (10.2 +/- 4.2 vs. 9.8 +/- 4.5 mg/l), and amlodipine (9.0 +/-
      6.0 vs. 8.5 +/- 5.4 mg/l) treatment. However, a significant decrease of plasma
      adiponectin concentration (from 11.6 +/- 4.6 to 10.2 +/- 4.2 mg/l, p = 0.047) was
      observed in patients treated with indapamide. Additionally in these patients, a
      significant increase of the HOMA-IR index was found (p = 0.021). CONCLUSION:
      Treatment with indapamide was followed by a significant decrease of plasma
      adiponectin concentration. This may participate in the pathogenesis of
      carbohydrate metabolism disturbances often found in patients treated with
      thiazide-type diuretics.

PMID- 17536227
TI  - Change in stroke incidence from a population-based intervention trial in three
      urban communities in China.
AB  - Stroke has been the main cause of death in most urban residents in China since
      the 1990s. A community-based intervention trial carried out in China aimed to
      reduce the incidence and mortality of stroke. In 1991, two well-matched
      communities each with approximately 50,000 people were selected as intervention
      or control communities in the urban areas of Beijing, Shanghai and Changsha.
      Regular health education and health promotion activities were carried out between
      1991 and 2000 in the intervention communities but no special action was taken in
      the control communities. Both fatal and nonfatal stroke cases were meticulously
      registered during the study in the two communities to assess the effect of long
      term intervention. The trend in stroke incidence and the effect of intervention
      on stroke incidence were analyzed using a Poisson regression model adjusted for
      age, sex, year and city. Between 1991 and 2000, 2,273 first-ever stroke cases
      were registered in the intervention communities and 3,015 in the control
      communities. Geographic variation and changes in the incidence of stroke and its
      subtypes were found among these 3 cities. Through 10 years of intervention,
      incidence risks of all, ischemic and hemorrhagic strokes decreased by 11.4%
      (relative risk 0.8959; 95% confidence interval, CI, 0.8483-0.9460; p < 0.0001),
      13.2% (relative risk 0.8676; 95% CI 0.8054-0.9345; p = 0.0002) and 7.2% (relative
      risk 0.9283; 95% CI 0.8517-1.0117; p = 0.0899), respectively, in the intervention
      compared with control communities. Accordingly, comprehensive community-based
      intervention measures could effectively reduce the incidence of stroke in the
      population.

PMID- 17536228
TI  - Obtaining medical records from healthcare facilities under the HIPAA Privacy
      Rule: the experience of a national longitudinal cohort study.
AB  - The processes for acquiring medical records from healthcare facilities in
      longitudinal cohort studies have not been well examined post-HIPAA Privacy Rule.
      We examined the response rates, correlates of response rates, and response times
      for obtaining patient medical records from healthcare facilities under the HIPAA
      Privacy Rule. Medical records were requested from facilities across the country
      on adults 45 or older enrolled in the national longitudinal cohort study REGARDS
      (Reasons for Geographic and Racial Differences in Stroke) who reported physician
      encounters for potential stroke events. From October 2003 to October 2006, 1,439
      medical records were received out of 1,518 reported eligible events (94.7%), with
      39 (2.6%) requests pending at the time of the analysis. The refusal rate for
      record requests from healthcare facilities was only 0.4%. The median length of
      time to receipt of a record was 26 days (range 1-679 days). Hospitals had the
      fastest return time (22 days from date of request to date of receipt) compared
      with outpatient clinics (28 days), doctor's offices (31 days), and long-term care
      facilities (55 days, p < 0.01). Healthcare facilities located in the Southern
      region had fastest return time compared with those in the Northwestern region (23
      vs. 46 days, p = 0.048). Medical records retrieval in prospective research
      studies is still feasible under HIPAA regulation.

PMID- 17536230
TI  - Abstracts of the 96th Annual Meeting of the United States and Canadian Academy of
      Pathology, March 24-30, 2007, San Diego, California, USA.

PMID- 17536229
TI  - Availability and costs of antiepileptic drugs and quality of phenobarbital in
      Vientiane municipality, Lao PDR.
AB  - PURPOSE: In developing countries, availability and quality of drugs are critical
      factors for effective management and control of epilepsy. This study investigated
      the availability and costs of antiepileptic drugs (AEDs), and the quality of
      phenobarbital in Vientiane Municipality, Lao PDR. METHODS: In March 2004, we
      enrolled all pharmacies (categories I and II) of four central districts of
      Vientiane eligible to sell AEDs. Two hundred and eight pharmacies of category III
      (75.1% of all registered pharmacies) were excluded as the sale of AEDs was not
      authorized. All pharmacists were interviewed with a standard questionnaire.
      Whenever phenobarbital was available, a sample was purchased and assayed by
      liquid chromatography. Phenobarbital was defined as being of correct quality if
      the active substance average content corresponded to +/-15% of the indicated
      amount. RESULTS: 66 pharmacies were enrolled (13 and 45 of categories I and II,
      respectively, and 8 hospital pharmacies). Six generics of AEDs were found
      (phenobarbital, phenytoin, valproic acid, clonazepam, carbamazepine, diazepam)
      and all pharmacies sold at least 1 AED. The 2 most widely available drugs were
      diazepam (5 mg) and phenobarbital (100 mg), present in 87.9 and 53.0% of the
      pharmacies, respectively. All 34 phenobarbital samples examined showed a correct
      concentration of the active compound. However, the concentration of phenobarbital
      100 mg tablets produced in Lao PDR (mean concentration 94.7 mg) was significantly
      lower (p = 0.005) than the imported equivalent (mean concentration 99.7 mg). The
      direct drug costs of a yearly treatment with phenobarbital were estimated to be
      at least 25.2 USD. CONCLUSIONS: A variety of AEDs are present. Their
      availability, particularly of phenobarbital, is restricted to higher-category
      pharmacies and within those it is rather limited. To meet the costs of AEDs in
      this setting is a major challenge for people with epilepsy. However, the quality
      of the available phenobarbital was rather satisfactory.

PMID- 17536231
TI  - Abstracts of the 96th Annual Meeting of the United States and Canadian Academy of
      Pathology, March 24-30, 2007, San Diego, California, USA.

PMID- 17536232
TI  - Abstracts from the 2006 CCFA National Research and Clinical Conference 5th Annual
      Advances in the Inflammatory Bowel Diseases, December 1-3, 2006, Miami, Florida,
      USA.

PMID- 17536233
TI  - Abstracts of Digestive Disease Week and ASGE (American Society for
      Gastrointestinal Endoscopy) Annual Postgraduate Course, May 2007, Washington, DC,
      USA.

PMID- 17536234
TI  - Current awareness in prenatal diagnosis.

PMID- 17536235
TI  - Abstracts of the 20th International Conference on Antiviral Research (ICAR),
      April 29-May 3, 2007, Palm Springs, California, USA.

PMID- 17536236
TI  - The EU clinical trials directive: 3 years on.

PMID- 17536237
TI  - Russia's prescription drugs crisis.

PMID- 17536238
TI  - The science and culture of sleeping and dreaming.

PMID- 17536239
TI  - Drama for doctors.

PMID- 17536240
TI  - Abstracts of the Annual Main Meeting of the Society for Experimental Biology, 31
      March-4 April 2007, Glasgow, Scotland.

PMID- 17536242
TI  - Abstracts of the 26th Annual Scientific Meeting of the American Pain Society, May
      2007.

PMID- 17536241
TI  - Abstracts of the 48th Annual Meeting of the Japanese Society of Plant
      Physiologists, March 28-30, 2007, Matsuyama, Japan.

PMID- 17536243
TI  - Cultural dynamics in HIV/AIDS biobehavioral research among young people.
      Proceedings of a workshop. September 2005. Bethesda, Maryland, USA.

PMID- 17536244
TI  - Docking the tail that wags the dog: banning drug reps from academic medical
      facilities.

PMID- 17536246
TI  - Proceedings of the 11th Interdisciplinary Slovak-Czech Toxicological Conference,
      Trencianske Teplice, Slovakia, June 5-7, 2006.

PMID- 17536245
TI  - Serial inebriate programs: what to do about homeless alcoholics in the emergency
      department.

PMID- 17536247
TI  - National Highway Traffic Safety Administration notes.   Rehabilitation costs and
      long-term consequences of motor   vehicle injuries.

PMID- 17536248
TI  - Centres of excellence: a Spanish cardiovascular research initiative. Interview by
      Jennifer Taylor.

PMID- 17536249
TI  - Viewpoint: Frank Enseleit, MD. Interview by Hannah Brown.

PMID- 17536250
TI  - The Eye and the Chip. Papers from the World Congress on Artificial Vision 2006.

PMID- 17536251
TI  - Challenges in the anticipation of biosimilars: how must a P&T committee gear up?

PMID- 17536252
TI  - Fomulary implications for the management of multidrug-resistant organisms.

PMID- 17536253
TI  - Red back spider bite.

PMID- 17536254
TI  - Infant mortality rate in India: still a long way to go.

PMID- 17536255
TI  - Carpal tunnel syndrome.

PMID- 17536256
TI  - Children's exposure to tobacco.

PMID- 17536257
TI  - Private provision in the UK National Health Service. The case for private
      provision in the NHS.

PMID- 17536258
TI  - [Current situation and future prospect of dermatovenereology].
AB  - Dermatovenereology have developed rapidly in fields including genodermatology,
      dermatological epidemiology, skin immunology, infectious skin diseases, clinical
      diagnosis, drug treatment, light therapy, and sexually transmitted diseases in
      recent years. Meanwhile, many skin diseases and a few venereal diseases still
      lack effective ways of treatment and control. More efforts should be made in both
      basic and clinical researches in the related fields.

PMID- 17536259
TI  - [Effects of triptolide on the production of interferon-gamma in human peripheral
      blood mononuclear cell and phosphorylation of signal transducer and activator of
      transcription-1 and production of interleukin-8].
AB  - OBJECTIVE: To investigate the effects of triptolide on the production of
      interferon-gamma (IFN-gamma) in human peripheral blood mononuclear cell (PBMC)
      and interleukin-8 (IL-8) in HaCaT keratinocytes and phosphorylation of signal
      transducer and activator of transcription-1 (STAT1) of IFN-gamma signal
      transduction pathways in HaCaT cells. METHODS: Human PBMC was induced by
      phytohaemagglutinin (PHA-L) and HaCaT cells were stimulated by recombinant human
      IFN-gamma (rhIFN-gamma). The productions of IFN-gamma and IL-8 in cells were
      detected by ELISA. The expression of STAT1 and its phosphorylation were analyzed
      by Western blot. RESULTS: Triptolide inhibited the production of IFN-gamma in
      human PBMC induced by PHA-L in a dose-dependent manner (P < 0.05, P < 0.01, P <
      0.001) and the 50% inhibitory concentration (IC50) value was 5.96 x 10(-11)
      mol/L. IL-8 production in HaCaT cells induced by rhIFN-gamma in vitro was also
      inhibited by triptolide (P < 0.001) and the IC50 value was about 1.15 x 10(-13)
      mol/L. The expressions of phosphorylated STAT1 in HaCaT cells stimulated by rhIFN
      gamma was inhibited by triptolide (P < 0.01) and the IC50 value was about 9.45 x
      10(-11) mol/L. CONCLUSION: Triptolide can inhibit the production of IFN-gamma in
      human PBMC and downregulate IL-8 level in HaCaT keratinocytes induced by rhIFN
      gamma. Triptolide can inhibit the phosphorylations of STAT1 of IFN-gamma signal
      pathway in HaCaT keratinocytes stimulated by IFN-gamma.

PMID- 17536260
TI  - [Identification of a novel mutation in the ATP2C1 gene in a Chinese pedigree with
      Hailey-Hailey disease].
AB  - OBJECTIVE: To study a Chinese pedigree with Hailey-Hailey disease (HHD) and
      examine the ATP2C1 gene mutation in this family. METHOD: All exons of ATP2C1 gene
      were analyzed with polymerase chain reaction and DNA sequencing in all patients
      of this family and 100 unrelated population-match controls. RESULTS: We
      identified a novel heterozygous nucleotide A --> G transition at position 235 - 2
      in intron 3 of ATP2C1 gene. This splice site mutation was not found in the
      healthy members of this pedigree and in the controls. CONCLUSION: The splicing
      mutation can affect the result of transcription and translation, and it is a
      specific novel mutation of ATP2C1 gene.

PMID- 17536261
TI  - [Effects of baicalin and other Chinese herbal monomer on androgen receptor mRNA
      expression in SZ95 sebocytes].
AB  - OBJECTIVE: To determine the effects of Chinese herbal monomers such as baicalin,
      berberine, and matrine on the androgen receptor (AR) mRNA expression in SZ95
      sebocytes in vitro and to explore the possible mechanism of using traditional
      Chinese medicines to treat acne. METHODS: SZ95 sebocytes were cultured and then
      treated with berberine, baicalin, matrine, and 13-cis-retinoic acid for 24 hours.
      Reverse transcription polymerase chain reaction was applied to detect the changes
      of AR. RESULT: AR mRNA was downregulated by 13-cis-retinoic acid of 1 x 10(-5)
      mol/L and 1 x 10(-6) mol/L, and by baicalin of 1 x 10(-4) mol/L (P < 0.05).
      CONCLUSION: 13-cis-retinoic acid and baicalin may exert antiandrogenitic action
      by inhibiting AR mRNA expression in human sebocytes.

PMID- 17536262
TI  - [Diagnosis and treatment of relapsing polychondritis].
AB  - OBJECTIVE: To explore the diagnosis and treatment of relapsing polychondritis
      (RP). METHODS: The clinical manifestations, diagnosis, and treatment of 24
      patients with RP were retrospectively analyzed. Twenty-four RP patients were
      examined for autoimmune antibody. Laryngoscopy was performed in 4 out of 6 RP
      patients with laryngeal involvement. Bronchoscopy was performed in 12 out of 19
      RP patients with lower respiratory tract involvement. Biopsies were taken from
      the cartilage involved in 16 out of 24 patients. RESULTS: Five patients were ANA
      positive at present, 2 patients were SSA antibody positive, 2 patients were anti
      RNP antibody positive, and 2 patients were anti-Sm antibody positive.
      Laryngoscopy revealed vocal fold edema and laryngeal stenosis. Bronchoscopy
      showed stenosis of trachea and both main bronchi and destruction of
      tracheobronchial cartilage. Histopathology revealed chronic inflammation of
      cartilage. Treatment included immunosuppressants (cyclophosphamide, methotrexate)
      together with prednisone. Eleven patients with respiratory tract involvement had
      laryngotracheostomy or airway stenting. Twenty-three patients alleviated after
      treatment, and 1 patients died. CONCLUSIONS: RP involves cartilage and connective
      tissue. Laryngotracheobronchial complications are the most severe manifestations
      of this disease. Corticosteroids and immunosuppressive drugs are effective
      treatment options. Patients with laryngotracheal stenosis and collapsed
      tracheobronchial wall should receive laryngostomy, tracheostomy, or airway
      stenting to improve airway obstruction symptoms.

PMID- 17536263
TI  - [Clinical characteristics of 51 patients with mycosis fungoides].
AB  - OBJECTIVE: To update the clinical characteristics of mycosis fungoides in Chinese
      patients. METHOD: We retrospectively analyzed the clinical data of 51 patients
      (29 men and 22 women) with mycosis fungoides in PUMC hospital from 1984 to 2006,
      to determine the ages at diagnosis, clinicopathologic characteristics of skin
      lesions, systemic manifestation, misdiagnosis and treatment of these patients.
      RESULTS: The mean age was (44.24 +/- 2.05) years at the diagnosis. Most patients
      were characterized by the typical evolution of patches, plaques and tumors, with
      some variations and subtypes. Clinical manifestations included generalized
      lesions (68.6%) and itchy (70.6%). Epidermotropism (68.6%) and Pautrier's
      microabscesses (52.9%) were common histopathologic features. The positive rate of
      T-cell receptor gene rearrangement was 81.3%, and was independent of the
      histological features. Previous misdiagnosis rate was 64.7%. Skin-targeted
      therapies and biologic therapies were effective approaches to relieve the skin
      rash at early stage, and combined chemotherapy was typically applied in more
      advanced cases. CONCLUSION: Mycosis fungoides has various clinical
      characteristics and careful differential diagnosis should be made in clinical
      practice.

PMID- 17536264
TI  - [Genotyping of genital human papillomavirus by DNA sequencing and luminex
      methods].
AB  - OBJECTIVE: To compare the specificity and sensitivity of two genotyping
      approaches for human papillomavirus (HPV). METHOD: HPV DNA was amplified and
      detected in clinical specimens by polymerase chain reaction in a pair of
      universal primers MY09/11, and then genotyped with either sequencing method or
      liquid chip hybridization method (luminex method). RESULT: Sequencing method
      obtained precise genotyping results in single-type HPV infection, while luminex
      method obtained accurate genotyping results in multiple-type HPV infection.
      CONCLUSION: A combined method using both sequencing and luminex method is
      suitable for the genotyping of HPV-infected specimens.

PMID- 17536265
TI  - [Pathogenicity of antibody subtypes against pemphigus vulgaris antigen
      extracellular 1-2 epitopes].
AB  - OBJECTIVE: To explore whether the antibody subtypes against the extracellular 1-2
      (EC1-2) epitopes of pemphigus vulgaris antigen (PVA) are related to the
      pathogenesis of PVA. METHODS: EC1-2 fusion protein, emulsified with complete
      Freund's adjuvant (CFA) or aluminum hydroxide hydrate [Al ( OH)3], was used to
      immunize C57BL/6 mouse. After immunization, the cytokine types, specific antibody
      titers, and antibody subtypes were detected. Also, a neonatal mice model was used
      to evaluate the pathogenesis of different antibodies. RESULTS: Th1 type cytokine
      interferon gamma (IFNgamma) was elevated in CFA group, while Th 2 type cytokine
      interleukin-4 (IL-4) was increased in Al (OH)3 group. The antibody subtypes were
      different in both groups. After the two groups were transferred with antisera
      separately, the neonatal mice developed erosion on the skin from Al(OH)3 group,
      with acantholysis histopathologically and bright immuno-fluorescence deposition,
      which was not seen in CFA group. CONCLUSION: Different antibody subtypes may
      contribute to the pathogenesis of disease.

PMID- 17536266
TI  - [Establishment of systemic lupus erythematosus-like murine model with Sm
      mimotope].
AB  - OBJECTIVE: To establish systemic lupus erythematosus (SLE) -like murine model by
      immunizing BALB/C mice with Sm mimotope. METHODS: Sm mimotope was identified by
      screening a 12-mer random peptide library with monoclonal anti-Smith antibody. Sm
      mimotope was initially defined with sandwich ELISA, DNA sequencing, and deduced
      amino acid sequence; and BALB/C mice were subcutaneously injected with mixture
      phages clones. Sera Sm antibody, anti-double stranded DNA (dsDNA) antibody, and
      antinuclear antibody (ANA) of mice were detected using direct immunofluorescence;
      kidney histological changes were examined by HE staining. RESULTS: Five randomly
      selected peptides were sequenced and the amino acid sequences IR, SQ, and PP were
      detected in a higher frequency. High-titer IgG autoantibodies of dsDNA, Sm, and
      ANA in the sera of experiment group were detected by ELISA 28 days after having
      been immunized by Sm mimotope. Proteinuria was detected 33 days later; immune
      complex and nephritis were observed in kidney specimens. CONCLUSION: SLE-like
      murine model can be successfully induced by Sm phage mimotope.

PMID- 17536267
TI  - [Effects of Malassezia isolates on cytokines production associated with
      melanogenesis by keratinocytes].
AB  - OBJECTIVE: To investigate the co-culture of keratinocytes with Malassezia
      isolates which cause the pityriasis versicolor with different color and to
      analyze the changes of cytokines associated with melanogenesis. METHODS: The
      effects of Malassezia species with different proportions on the growth rate of
      keratinocytes was assessed with 5 g/L methyl thiazolyl tetrazolium (MTT). Co
      culture of keratinocytes and Malassezia species were performed with isolates from
      hyer- and hypo-pigmentation areas of pityriasis versicolor. The supernatants were
      collected at different time points, and the changes of basic fibroblast growth
      factor (b-FGF), endothelin-1 (ET-1), nerve growth factor-beta (NGF-beta),
      interleukin-1alpha (IL-1alpha), interleukin-6 (IL-6), tumor necrosis factor-alpha
      (TNF-alpha), stem cell factor (SCF) were recorded. Three control groups were
      established accordingly. RESULTS: When the ratio between keratinocytes and
      Malassezia species was lower than 1: 10, the growth rate of keratinocytes was not
      affected by Malassezia (P > 0.05). When the ratio was increased above 1:20, the
      growth rate of keratinocytes was significantly inhibited by Malassezia (P <
      0.01). The secretions of IL-1alpha, IL-6, TNF-alpha, and ET-1 was significantly
      increased after the co-culture of keratinocytes and Malassezia (P < 0.01), while
      those of b-FGF, NGF-beta, and SCF had no significant changes (P > 0.05). Compared
      with the isolates from the hypo-pigmentation area, ET-1 induced by isolate from
      hyperpigmentation area significantly increased (P < 0.01). CONCLUSION: When
      Malassezia isolates are co-cultured with keratinocytes, the secretions of
      cytokines associated with melanogenesis may differ from each other. ET-1 may play
      certain role in the hyper-pigmentation of pityriasis versicolor.

PMID- 17536268
TI  - [Genetical diagnosis in a family with X-linked hypohidrotic ectodermal
      dysplasia].
AB  - OBJECTIVE: To identify the mutations of ED1 gene in a family with X-linked
      hypohidrotic ectodermal dysplasia METHODS: Eight coding exons of ED1 gene of two
      patients with clinically confirmed X-linked hypohidrotic ectodermal dysplasia,
      their parents, and 100 unrelated population-matched control were amplified by
      polymerase chain reaction. The products were further analyzed by direct
      sequencing. RESULTS: Two patients with X-linked hypohidrotic ectodermal dysplasia
      in this pedigree showed a point mutation at nucleotide 1 045 ( A > G) .
      Meanwhile, heterozygous double peaks of nucleotide G and A at the same position
      were found in their mother, but not in their father and 100 unrelated population
      matched controls. CONCLUSION: The c. 1 045A > G mutation of ED1 gene may be the
      pathologic cause of this Chinese family with X-linked hypohidrotic ectodermal
      dysplasia.

PMID- 17536269
TI  - [Analysis of gene mutations in two patients with tuberous sclerosis complex].
AB  - OBJECTIVE: To analyze the mutation of TSC gene in two sporadic patients with
      tuberous sclerosis complex (TSC). METHODS: All the coding exons of TSC1 and TSC2
      genes of these two patients, unaffected member in the two families, and 100
      unrelated population-matched controls were amplified by polymerase chain
      reaction. The products were analyzed by direct sequencing. RESULT: Two TSC2 gene
      mutations (c. 268C > T, c. 5 227C > T) were identified in two patients, but not
      in their family members and in 100 unrelated population-matched controls.
      CONCLUSION: These two mutations are the cause of the clinical phenotypes of these
      two sporadic patients with TSC.

PMID- 17536270
TI  - [Effect of tacrolimus on the growth cycle of murine hair follicles].
AB  - OBJECTIVE: To explore the effect of tacrolimus on murine hair follicle cycle.
      METHOD: Hematoxylin-eosin dyeing and reverse transcription-polymerase chain
      raction techniques were used. RESULTS: Five days after depilation, the hair
      follicles in both the tacrolimus group and the minoxidil group was in anagen V,
      while that in the vaseline group was in anagen III. vascular endothelial growth
      factor (VEGF) and hepatocyte growth factor (HGF) were detected in back skin in
      both the tacrolimus group and the minoxidil group, but not in the vaseline group.
      CONCLUSION: Tacrolimus can promote the growth of hair by stimulating the hair
      follicle to enter anagen V in mice, which may be explained by the effects of VEGF
      and HGF.

PMID- 17536271
TI  - [Effects of antisense epidermal growth factor receptor oligodeoxynucleotides on
      ultraviolet-induced c-jun activity of keratinocytes].
AB  - OBJECTIVE: To explore the effects of antisense epidermal growth factor receptor
      (EGF-R) oligodeoxynucleotides on ultraviolet-induced c-jun activity of
      keratinocytes after EGF-R oligodeoxynucleotides transfect to HaCaT in vitro.
      METHODS: c-jun DNA binding activity after ultraviolet-B (UVB) irradiation and EGF
      R oligodeoxynucleotides transfection were determined with a highly sensitive and
      specific colorimetric method. After EGF-R oligodeoxynucleotides transfection, the
      mRNA level of EGF-R was detected by reverse transcription polymerase chain
      reaction method. RESULTS: Compared with control groups, c-jun activity increased
      significantly in UVB (10, 20, 30 mJ/cm2) irradiation groups (P < 0.05). EGF-R
      mRNA and c-jun activities induced by UVB were inhibited after the keratinocytes
      were transfected with EGF-R antisense oligodeoxynucleotides at 2, 4 and 8
      microg/ml concentrations (P < 0.01). CONCLUSION: The ultraviolet-induced c-jun
      activity of keratinocytes can be mediated by EGF-R and inhibited by EGF-R
      antisense oligodeoxynucleotides, which is transfected to keratinocytes and
      mediated by lipofectamine.

PMID- 17536272
TI  - [Effect of hypoxia inducible factor-1alpha on cells of hair follicle].
AB  - OBJECTIVE: To investigate the feasibility of stable transfection of human hypoxia
      inducible factor-1alpha (HIF-1alpha) gene into fibroblasts cells and the effects
      of supernatant from the transfected cell culture on hair follicle cells. METHODS:
      PcDNA-HIF1alpha was stably transfected into fibroblasts cells with lipofectamine
      2000. Expression of HIF-1alpha was observed by reverse transcription-polymerase
      chain reaction (RT-PCR) and Western blot. The supernatant was obtained to detect
      the expression of vascular endothelial growth factor (VEGF) by ELISA. The mRNA
      expression of basic fibroblast growth factor (bFGF) was detected by RT-PCR. MTT
      was used to detect the activity of fibroblasts cells and dermal sheath cells
      added with supernatant. RESULTS: PcDNA-HIF1alpha was successfully transfected
      into fibroblasts cells. HIF-1alpha could be detected by RT-PCR and Western blot.
      The expression of VEGF in the supernatant of cells transfected with PcDNA
      HIF1alpha was detected. The mRNA expression of bFGF was significantly higher than
      in the control group (P < 0.01). MTT showed the activity of cells added with
      supernatant was enhanced (P < 0.05). CONCLUSION: PcDNA-HIF1alpha can stably
      transfected into fibroblasts cells, and the expressed HIF-1alpha induces the
      expression of VEGF and bFGF, and the expressed VEGF enhances the activity of
      cells.

PMID- 17536273
TI  - [Expression and purification of tissue factor pathway inhibitor in Pichia
      pastoris].
AB  - OBJECTIVE: To generate recombinant human tissue factor pathway inhibitor (TFPI)
      in Pichia pastoris. METHODS: To improve the expression of TFPI, a silent mutation
      was generated at the specific site of TFPI cDNA. Both wild-type TFPI cDNA and
      mutated TFPI cDNA were cloned into the expression vector pPic9. The constructed
      plasmids were subsequently transformed into Pichia pastoris cells GS115 and KM71,
      and the transformants were confirmed by polymerase chain reaction and DNA
      sequencing. The expression of recombinant protein was induced by addition of 0.5%
      methanol in the culture medium. The cell culture medium after induction was
      concentrated through ultra filtration. The recombinant protein was further
      purified by a three-step process (Heparin-sepharose CL-6B affinity
      chromatography, DEAE-Sepharose Fast Flow affinity chromatography, and Sephadex
      G75-gel filtration). The amount of the recombinant protein was quantified with
      gel imaging system. The activity of the recombinant protein was analyzed by the
      chromogenic substrate assay. RESULTS: The amount of TFPI expressed in the mutated
      clone (1 mg/L) was much higher than that in the wild type clone (0.1 mg/L). The
      TFPI activity in the recombinant GS115 cells could be detected 12 hours after
      induction and reached the peak at 36 hours, while the TFPI activity in the
      recombinant KM71 cells started to show up at 24 hours after induction and reached
      the peak at 72 hours. The expression of recombinant protein in the silent mutant
      was significantly higher than those of wild type clone in both GS115 and KM71
      host cells. The relative molecular mass of recombinant TFPI was approximately 42
      000. CONCLUSION: Introduction of the silent mutation at the specific site of TFPI
      cDNA can increase the recombinant protein expression in Pichia pastoris, which is
      much higher than that in insect cells or saccharomyces cerevisiae.

PMID- 17536274
TI  - [Experiences of cardiopulmonary bypass for heart transplantation].
AB  - OBJECTIVE: To summarize the experiences of cardiopulmonary bypass (CPB)
      techniques in 15 patients of orthotopic heart transplantation. METHODS: All
      patients received mild hypothermia and high flow rate perfusion. Effective
      strategies were taken to protect myocardium, lung, kidney, and blood
      conservation. The donor hearts were arrested with aorto perfusion using 1 000 ml
      St. Thomas solution at 4 degrees C, perfused with 1 000 ml University of Wiscosin
      (UW) solution or Histidin-Tryptophan-Ketoglutarat (HTK) solution at 4 degrees C,
      and then preserved in ice saline. Ice mud was covered on the donor heart during
      anastomosis. Low potassium cardioplegia solution was perfused before the
      unclamping of aorta. RESULTS: The CPB time was (165.2 +/- 22. 8) min, the warm
      ischemia time was ( 7. 7 +/- 1. 7) min, and the cold ischemia time was ( 142. 4
      +/- 11. 5) min. Heart beats was automatically recovered in 10 patients, and was
      recovered upon defibrillation in 5 patients. Left ventricular ejection fractions
      were (64. 1 +/- 4. 6) % after one month. All patients survived. CONCLUSION:
      Proper CPB management and effective donor heart protection are essential to
      guarantee the success of heart transplantation.

PMID- 17536275
TI  - [Characterization and diagnostic accuracy of serous cystadenomas and mucinous
      neoplasms of the pancreas with multi-slice helical computed tomography].
AB  - OBJECTIVE: To evaluate the feasibility of using multi-slice helical computed
      tomography (MS-CT) to accurately distinguish serous cystadenomas from mucinous
      cystadenomas or cystadenocarcinomas of the pancreas and to determine their
      radiographic appearances that can be applied for differentiative diagnosis.
      METHODS: We performed a single-blind retrospective analysis of CT images of 30
      patients with pathologically proven primary cystic pancreatic neoplasms (12 cases
      of serous cystadenomas, 14 cases of mucinous cystadenomas, and 4 cases of
      mucinous cystadenocarcinomas) to reach a diagnosis of either serous cystadenoma
      or mucinous cystic tumor. CT features such as tumor location, septations,
      presence of calcification, features of cystic wall, papillary excrescences, and
      size of the largest cyst were recorded. Statistical analysis was performed to
      evaluate the efficacy of certain CT findings in the differentiation of serous
      cystadenomas and mucinous neoplasms. RESULTS: Totally 9 (75.0%) serous
      cystadenomas and 16 (88.9%) mucinous tumors were correctly diagnosed. Three
      serous cystadenomas were misdiagnosed as mucinous cystadenomas, while 2 mucinous
      neoplasms were misdiagnosed as serous cystadenomas. And 9 (75.0%) serous
      cystadenomas were located at the pancreatic head and neck areas, while 12 (66.7%)
      mucinous neoplasms were located at the pancreatic body and tail areas (P < 0.05).
      The presence of calcification, especially central calcification, had statistical
      significance in differentiating serous cystadenoma from mucinous neoplasms (P <
      0.05). The size of the largest cyst over 2 cm was positive associated with
      mucinous neoplasms (P < 0.05). CONCLUSION: CT characteristics between serous
      cystadenomas and mucinous neoplasms of the pancreas have distinct difference,
      which validates the values of CT in differentiating these tumors. However,
      atypical CT appearances may compromise its diagnostic accuracy.

PMID- 17536276
TI  - [Determination and clinical significance of serum anti-ryanodine receptor
      antibody in patients with myasthenia gravis].
AB  - OBJECTIVE: To explore the clinical significance of serum anti-ryanodine receptor
      (RyR) antibody in the diagnosis of myasthenia gravis (MG). METHODS: The crude
      sarcoplasmic reticulum was prepared from rabbit skeletal muscle, and then
      purified by differential centrifugation to produce the antigen. The serum anti
      RyR antibody levels in 74 patients with MG (including 21 patients with comorbidic
      thymomas) were determined with ELISA. RESULTS: Western blot demonstrated the
      presence of RyR in purified crude sarcoplasmic reticulum. The positive rate of
      anti-RyR antibody was significantly higher in MG patients who had comorbidic
      thymoma compared with those who had no such comorbidity (P < 0.01). Also, the
      positive rate was closely correlated with the severity of MG. CONCLUSION: Serum
      anti-RyR antibody test is helpful in the diagnosis of MG associated with thymoma
      and can be used to judge the outcome of MG.

PMID- 17536277
TI  - [Regulation of tyrosylprotein sulfotransferases activity by sulfotyrosine].
AB  - OBJECTIVE: To investigate the role of sulfated tyrosine in regulating the
      activity of tyrosylprotein sulfotransferases (TPST) 1 and TPST2. METHODS:
      Constructs of TPST 1 and TPST2 were amplified by polymerase chain reaction (PCR),
      then fused into immunoglobulin G1 Fc region. All the variants in which sulfated
      tyrosines were mutated to phenylalanine were made by the PCR-based Quick Change
      method and confirmed by sequencing the entire reading frame. Small hairpin RNA
      (shRNA) constructs-targeting nucleotides 259-275 of TPST1 and nucleotides 73-94
      of TPST2 were generated and subcloned into pBluescript. Human embryonic kidney
      (HEK) 293T cells were transfected with these plasmids. One day later, cells were
      split: one part was labeled with 35S-cysteine and methionine or 35S-Na2SO3
      overnight, the second part was used for 125I labeled binding experiment, and the
      third part was retained for binding and flow cytometry. RESULTS: Tyrosines at
      position 326 of TPST1 and position 325 of TPST2 were sulfated
      posttranslationally. Tyrosine sulfation of TPSTs was effectively inhibited by
      sulfation inhibitors, including specific shRNAs and non-specific NaCIO3. shRNAs
      reduced the sulfation of C3a receptor and C5a receptor, and partially blocked the
      binding of these two receptors to their respective ligands. CONCLUSIONS: The
      activities of TPSTs were regulated by tyrosine sulfation. Inhibition of
      sulfotyrosine decreases the binding ability of C3a receptor and C5a receptor to
      their respective ligands.

PMID- 17536279
TI  - [Effects of medical treatment on apoptosis in eutopic endometrium of patients
      with endometriosis].
AB  - OBJECTIVE: To investigate the apoptosis-related mechanisms of levenorgestrel
      releasing intrauterine system (LNG-IUS), oral medroxyprogesterone (MPA), and
      injective gonadotrophic hormone releasing hormone agonist (GnRHa) on eutopic
      endometrium of patients with endometriosis. Methods We collected the samples of
      endometrium from patients with endometriosis before operation and after insertion
      of LNG-IUS, administration of oral MPA, or injection of GnRHa. The ultrastructure
      of endometria was observed and compared by electron microscopy. Apoptotic cells
      were assessed by the terminal deoxynucleotidyl transferase-mediated deoxy-UTP
      nick-end labeling (TUNEL) assay, and the expressions of Bax, Fas, and Fas-L mRNA
      were determined by semi-quantitative reverse transcription-polymerase chain
      raction. Results After have been exposured to LNG-IUS, the apoptotic rate of
      endometrial epithelial cells and stromal cells increased from (24. 4 +/- 35.0)%
      to (51.0 +/- 37.8)% (P = 0.027) and (35.3 +/- 30.2)% to (76.4 +/- 11.2)% (P =
      0.008), respectively. The degree of apoptosis under transmission electron
      microscopy was in an order of GnRHa > LNG-IUS > MPA. The expression of Fas-L mRNA
      in eutopic endometrium of patients with endometriosis was significantly higher
      than that of the normal control (P < 0.05). The expressions of three apoptosis
      related proteins had no significant difference. CONCLUSION: Medical treatments
      can increase the apoptosis of eutopic endometrial cells, and such effect was
      strongest in GnRHa and relatively weaker in LNG-IUS and MPA.

PMID- 17536278
TI  - [Effects of adenovirus delivered tissue inhibitor of metalloproteinases
      transfection on biological behaviors of cervical cancer cell lines].
AB  - OBJECTIVE: To explore the effects of adenovirus delivered tissue inhibitor of
      metalloproteinases-3 (Ad-TIMP-3) on the biological behaviors of cervical cancer
      cell lines and to evaluate its potential application in cervical cancer gene
      therapy. METHODS: We transferred Ad-TIMP-3 into cervical cancer cells. The TIMP-3
      mRNA expression was assessed by RT-PCR, and the TIMP-3 and p53 protein
      expressions were assessed with Western blot. The apoptotic changes of cells were
      illustrated with morphology and DAPI staining. The viability of cells was
      determined with MTT assay. The abilities of in vitro invasion and adhesion were
      evaluated by the invasion and adhesion assays respectively. RESULTS: After
      infection, the TIMP-3 mRNA and protein were significantly upregulated in a time
      dependent manner. Overexpression of TIMP-3 markedly increased p53 protein level
      in spite of the backgrounds of p53 gene in cells. Ad-TIMP-3 infection induced
      massive apoptosis of cervical cancer cells with a marked bystander effect. The
      abilities of in vitro invasion and adhesion were inhibited significantly (P <
      0.01). The cytotoxicity of Ad-TIMP-3 was significantly stronger than that of Ad
      p53 (P < 0.05, P < 0.01). CONCLUSIONS: Ad-TIMP-3 infection has cytotoxic effects
      on cervical cancer cells and can inhibit the expressions of these malignant
      phenotypes. Ad-TIMP-3 may be a potentially useful agent for cervical cancer gene
      therapy.

PMID- 17536280
TI  - [Effects of progesterone and progestin on expression of regulated on activation,
      normal T cell expressed and secreted in eutopic endometrium from patients with
      endometriosis].
AB  - OBJECTIVE: To investigate the effects of progesterone and progestin on the
      expressions of regulated on activation, normal T cell expressed and secreted
      (RANTES) in eutopic endometrium from patients with endometriosis. METHODS: We
      collected the samples of endometrium from patients with endometriosis before
      operation or after insertion of levenorgestrel releasing intrauterine system (LNG
      IUS), administration of oral medroxyprogesterone (MPA), or injection of
      gonadotrophic hormone releasing hormone agonist (GnRHa). Reverse transcription
      polymerase chain raction was used to assay the expression of RANTES mRNA. On the
      other hand, progesterone (Po) and tumor necrosis factor-alpha (TNFalpha) of
      different concentrations and different manners were used to treat cultured cells
      in vitro. RANTES secretion was evaluated in the culture medium using ELISA. In
      order to evaluate the effect of Po on the secretion of RANTES under stimulation
      of TNFalpha, the cells were cultured in medium containing 100 U/ml TNFalpha and
      Po of different concentrations for 24 hours. After the pretreatment of Po for 48
      hours at different concentrations, TNFalpha (100 U/ml, 16 h) was added to observe
      whether Po inhibits RANTES or not. RESULTS: The expression of RANTES mRNA in
      eutopic endometrium of patients with endometriosis was significantly higher than
      in control group (28.0 +/- 9.0 vs. 22.0 +/- 5.6, P < 0.05). Following the
      exposures to LNG-IUS (24.0 +/- 4.2 vs. 25.9 +/- 4.2, P > 0.05) or GnRHa (23.0 +/-
      12.9 vs. 26.9 +/- 5.2, P > 0.05), the expression of RANTES mRNA had no change.
      MPA significantly increased the expression of RANTES mRNA (42.6 +/- 3.1 vs. 24.3
      +/- 5.7, P < 0.05). Po itself had no significant effect on the secretion of
      RANTES. Stimulated by Po and TNFalpha at the same time, the secretion of RANTES
      significantly increased. After pretreatment with Po for 48 hours, the reaction of
      RANTES to the stimulating effect of TNFalpha was down-regulated. CONCLUSION: The
      eutopic endometrium of patients with endometriosis has high chemotactic activity.
      It may be feasible to prevent and treat endometriosis with progestins.

PMID- 17536281
TI  - [Neovascularization potential of mobilized peripheral mononuclear cells from
      diabetes patients].
AB  - OBJECTIVE: To determine whether mobilized peripheral blood mononuclear cells (M
      PBMNCs) obtained from patients with diabetes was impaired in therapeutic
      neovascularization in limb ischemia, and to explore the pathological mechanisms
      of the impairment. METHODS: Endothelial progenitor cells (EPC) were cultured in
      EGM-2MV, and then characterized by uptake of 1, 1-dioctadecyl-3, 3, 3, 3
      tetramethylindocarbocyanine-labeled acetylated low density lipoprotein (Dil
      AcLDL) and binding of ulex europaeus agglutinin (UEA). The number of EPC was
      compared between M-PBMNCs obtained from diabetic patients and those from normal
      subjects. M-PBMNCs obtained from diabetic patients, M-PBMNCs obtained from normal
      controls, or PBS were injected into the ischemic limbs of streptozotocin-induced
      diabetic nude mice. The limb blood perfusion was detected by laser Doppler blood
      perfusion imaging between these three groups in the following 1, 3, 7, 14, 21,
      and 28 days. Ambulatory score and ischemia damage were evaluated in the following
      4 weeks. Capillary/fiber ratio was detected by CD31 or BS-1 lectin, and arteriole
      density was detected by alpha-smooth muscle actin (alpha-SMactin). RESULTS: The
      number of EPC from diabetic patients were positively correlated with the blood
      perfusion (R = 0.486, P < 0.05) and capillary density (R = 0.491, P < 0.05), and
      the EPC number in diabetic patient were negatively correlation with their disease
      courses (R = - 0.587, P < 0.05). Transplantation of diabetic M-PBMNCs augmented
      the blood perfusion of ischemia hindlimbs, increased the capillary and arteriole
      densities, and promoted the collateral vessel formation. However, all the
      improvements were less significant in the diabetic patients than in the non
      diabetic patients (P < 0.05). CONCLUSION: Diabetes decreased the capability of M
      PBMNCs to augment neovascularization in ischemia.

PMID- 17536282
TI  - [Advancements in melanocytes in hair follicle].
AB  - Melanoblasts, the precursors to melanocytes, originate in the neural crest. Some
      melanoblasts can travel to the hair follicle and further differentiate into
      pigment melanin-producing melanocytes. Hair follicles contain a pool of
      undifferentiated melanocyte stem cells (MSCs), which are sources of
      differentiated melanocytes, and functional melanocytes exhist in the hair bulb.
      The volume, life, and activity of melanocytes in a hair follicle is closely
      related with the growth cycle of follicle. Appearance of gray hair gray results
      from incomplete MSCs maintenance.

PMID- 17536283
TI  - [Sebaceous glands and acne].
AB  - New studys on the sebaceous glands in recent years have facilitated the further
      understanding and treatment of acne vulgaris. This article summarizes the
      advancements in the relationship between sebaceous glands and acne, with focus on
      androgen metabolism in skin, abnormal lipids secretion, and immunology of
      sebaceous gland cells.

PMID- 17536284
TI  - [Photoaging: laser and light-based therapy].
AB  - Photoaging is clinical character by dyspigmentations, telangiectacia, and
      wrinkles. Therefore, the assessment of therapeutic effects of photoaging depends
      on the management results of these three lesions. This article introduces the
      effect of laser and light-based therapies on photoaging.

PMID- 17536285
TI  - [Advancements in expression of vascular endothelial growth factor receptors in
      skin diseases].
AB  - Vascular endothelial growth factor (VEGF) exerts its biological functions by its
      specific VEGF receptors (VEGFR), which includes VEGFR-1, VEGFR-2, VEGFR-3,
      neuropilin-1, and neuropilin-2. These VEGFR distributes in endothelial cells, and
      are also expressed in normal skin, inflammatory skin diseases, and skin cancers.
      The VEGF-VEGFR signaling pathway may be a new key target in the management of the
      skin diseases.

PMID- 17536286
TI  - [Genetic diagnosis of polycystic kidney disease using single cell fluorescent
      polymerase chain reaction].
AB  - OBJECTIVE: To explore the feasibility of using single cell fluorescent polymerase
      chain reaction (PCR) in the preimplantation genetic diagnosis (PGD). METHOD:
      Single buccal cell genetic analysis was performed with fluorescent PCR of linked
      microsatellite D16S423, followed by electrophoresis on ABI 3730. RESULT: The
      amplification success rate, allele dropout rate, and diagnostic accuracy rate of
      the single cell fluorescent PCR were 93.3%, 10.7%, and 89.3%, respectively.
      CONCLUSION: Single cell fluorescent PCR is a stable and reliable approach for the
      PGD.

PMID- 17536287
TI  - From bench to bedside: advances in stem cell biology and gene therapy.

PMID- 17536288
TI  - Koo DW, Fish WW. Spinal cord injury and snowboarding: the British Columbia
      experience. J Spinal Cord Med. 1999; 22(4):246-251.

PMID- 17536289
TI  - The relationships among serum lipid levels, adiposity, and depressive
      symptomatology in persons aging with spinal cord injury.
AB  - BACKGROUND: Cardiovascular disease (CVD) appears to occur prematurely in persons
      with spinal cord injury (SCI). Stress may play a significant role in the
      development of CVD. Depression is the most common form of stress complicating the
      care of persons with SCI. METHODS: In 188 persons with SCI, 46% with tetraplegia
      and 54% with paraplegia, the relationship between depression and the serum lipid
      profile was studied. Depression was measured by the Older Adult Health and Mood
      Questionnaire (OAHMQ) for persons with disability. Total cholesterol, high
      density lipoprotein (HDL) and low density lipoprotein (LDL) cholesterol and
      triglycerides were measured; body mass index (BMI) was computed and percent body
      fat was determined by dual-energy x-ray absorptiometry (DXA). RESULTS: Depression
      and level of SCI were found to have significant interactive effects on serum
      lipid levels. Serum total and LDL cholesterol, as well as triglycerides, were all
      higher among persons with paraplegia who were depressed compared to those who
      were not depressed. This was not found in persons with tetraplegia. Inverse
      relationships were evident between serum triglycerides and HDL cholesterol
      levels. Persons with paraplegia who were depressed had significantly more
      adiposity than those not depressed. BMI correlated directly with serum
      triglycerides and indirectly with serum HDL cholesterol. CONCLUSION: Depression
      appears to be a strong determinant of adverse lipid profiles in patients with
      paraplegia. association between depression and adiposity in these patients
      compounds the risk for cardiovascular disease.

PMID- 17536290
TI  - A randomized blinded comparison of two methods used for venous antistasis in
      tetraplegia.
AB  - OBJECTIVE: The hemodynamic effects of slow sequential compression (SCD) were
      compared with rapid intermittent pulsatile compression (IPC) in subjects with
      complete tetraplegia. METHODS: Twenty subjects underwent Doppler examination of
      the bilateral popliteal and femoral veins. Resting volume flow per minute (VFM),
      average venous velocity (AVV), and maximal venous velocity (MVV) were measured in
      both veins. SCD and IPC were then randomly applied to one limb each, followed by
      repeat Doppler measurements under compression conditions. Doppler spectral
      recordings were stored for future analysis, and then measured by an investigator
      blinded to testing conditions (rest versus compression) and device (SCD versus
      IPC). RESULTS: Sequential compression and IPC compression both increased
      popliteal and femoral vein VFM, AVV, and MVV above resting levels (all p's <
      0.001). In the femoral vein VFM (p < 0.05) and MVV (p < 0.05) were augmented
      during IPC compared to SCD compression. CONCLUSION: As MVV best reflects
      performance effectiveness of compression devices, these data find IPC more
      effective than SCD for stimulating venous blood flow in subjects with
      tetraplegia.

PMID- 17536291
TI  - A comparative study of outcomes and expenses following tetraplegia and
      paraplegia.
AB  - OBJECTIVE: A study was designed to directly compare individuals with tetraplegia
      and paraplegia to further explore neurological and functional outcomes and their
      impact on the expense of rehabilitation when controlling for level of
      completeness, age at the time of injury, and length of stay. METHODS: A sample
      was drawn from the National Spinal Cord Injury Database consisting of 2069
      individuals, 1005 with paraplegia and 1064 with tetraplegia. RESULTS: Significant
      demographic differences were found between the 2 groups with regard to age,
      ethnicity, marital status, and employment status. Significant differences were
      found between the groups with regard to all individual outcome variables (p <
      .001) and expenses (p < .05). On average, patients with paraplegic injuries
      evidenced greater change and efficiency on a functional independence measure than
      patients with tetraplegia. In contrast, patients with tetraplegia showed greater
      changes and efficiency with regard to ASIA Motor Index scores. Higher
      rehabilitation expenses were found for patients with tetraplegia.

PMID- 17536292
TI  - Charcot shoulder joint associated with syringomyelia: a case report.
AB  - A 36-year-old man with degenerative disease of the spine and cervical
      syringomyelia (syrinx) presented with new weakness and numbness in his left upper
      extremity. Examination revealed decreased range of motion (ROM), swelling,
      weakness, and diminished pinprick, vibratory, and proprioceptive sensation in the
      left upper extremity. Radiographic examination showed a severe destructive
      arthropathy; a biopsy ruled out malignancy. A culture was negative for infection,
      and a repeat magnetic resonance imaging (MRI) showed a patent syringo-peritoneal
      shunt with no change in syrinx size. He was diagnosed with a Charcot shoulder.
      Treatment consisted of nonsteroidal anti-inflammatory medication, passive motion
      exercises, and a protective sling. The patient with syringomyelia may experience
      sensory loss that prevents normal guarding, resulting in repetitive trauma and
      eventual joint destruction. Appropriate assessment, diagnostic work-up, and
      treatment are essential in the management of the Charcot joint. Patient
      education, including information on activities that may be harmful, must be
      included, as such knowledge may slow or prevent the impairment that comes with a
      Charcot joint.

PMID- 17536293
TI  - Use of capsaicin in the treatment of radicular pain in spinal cord injury.
AB  - BACKGROUND: Pain following spinal cord injury (SCI) is a common problem and can
      interfere with functional recovery. Radicular pain (pain at the level of injury)
      is one type of SCI pain. Traditional analgesic agents are sometimes ineffective
      and can have significant systemic side effects. METHODS: A retrospective review
      of 8 patients with radicular pain secondary to SCI who responded to topical
      capsaicin therapy. FINDINGS: Improvement was noted in 1-2 weeks, including 1
      patient with a 12-year history of intractable pain. Long-term efficacy was seen
      in 2 patients treated for >2 years. CONCLUSION: Based on these favorable results
      and minimal side effects, topical capsaicin should be considered in the treatment
      of localized radicular pain secondary to SCI.

PMID- 17536294
TI  - Comparison of parenting styles of persons with and without spinal cord injury and
      their children's social competence and behavior problems.
AB  - OBJECTIVE: This study compared the parenting styles of 62 individuals with spinal
      cord injury (SCI) and 62 individuals without disabilities and the behavior of
      their children aged 6 through 13 years. METHODS: The relationship between
      parenting style and children's behavior was assessed. Pairs were matched by
      gender of parent and age and gender of child. The Parenting Dimensions Inventory
      and the Child Behavior Checklist were administered via telephone. RESULTS: After
      controlling for income, the 2 groups did not differ in the parenting factors of
      warmth/structure and strictness. Their children did not differ in social
      competence or behavior problems. CONCLUSION: Regardless of disability status,
      warmth and structure were found to be the aspects of parenting that were related
      to children's outcomes.

PMID- 17536295
TI  - Characteristics of persons with spinal cord injury as documented by use of an
      interactive data system.
AB  - RATIONALE: Physicians need information about their rehabilitation practices that
      shows the types of patients being seen and the outcomes for their rehabilitation
      programs. In order to obtain more information on secondary medical complications
      and prevention programs, and to provide the information to the spinal cord injury
      (SCI) rehabilitation team, an interactive data management system was developed.
      RESULTS: Initial findings for the first 99 patients with SCI were presented for
      staff review. Demographic information indicated that patients typically lived in
      private residences, had at least a high school education, and had annual incomes
      < $20,000. There were nearly equal numbers of paraplegic and tetraplegic
      patients; 63% of patients were more than 50 years of age and 69% were more than
      10 years post-injury. Over 80% of the patients reported satisfactory health, were
      physically active, and had adequate transportation. Paraplegic and tetraplegic
      patients had similar profiles for secondary complications. CONCLUSIONS: The SCI
      staff was surprised that greater than 35% of patients with SCI reported current
      problems with spasticity, pain, and pressure ulcers. The staff was interested in
      obtaining additional patient-perception information including the severity of
      each problem, how the problem interfered with daily activity, and the desire for
      additional care. The staff felt that patients were reporting problems more often
      to the interviewer than to their physician. There was unanimous support for the
      ongoing collection of patient-perception information.

PMID- 17536296
TI  - Social and personal consequences of acquired bowel dysfunction for persons with
      spinal cord injury.
AB  - BACKGROUND: Traditional literature regarding acquired bowel dysfunction for
      persons with spinal cord injury (SCI) has focused on clinical assessments of
      bowel dysfunction and bowel management programs. These studies make reference to
      the effects of bowel dysfunction on quality of life (QOL), but none
      systematically study the relationship. This study develops 4 scales that measure
      impediment to community integration (ICI) due to bowel dysfunction and then
      examines the relationship between bowel dysfunction, ICI, and QOL. METHODS: A
      structured telephone survey was conducted with a convenience sample of 103 SCI
      consumers. Survey questions documented bowel dysfunction (ie, severity and number
      of accidents), bowel management (ie, how often bowels are evacuated), ICI, and
      satisfaction with 4 life domains. RESULTS: Correlation analyses showed that
      subjective bowel dysfunction severity and number of days per month a respondent
      had to stay home because of lack of bowel control were associated with barriers
      to personal relationships, feelings about self, and home life. Also, the number
      of bowel accidents per month was associated with feelings about self. ICI scales
      were shown to be related to lower levels of satisfaction with free time,
      friendships, family life, and life in general. No statistically significant
      relationships were found between bowel dysfunction and satisfaction with life.
      CONCLUSION: Bowel dysfunction is a barrier to community integration and is
      related to low levels of life satisfaction. Also, it is possible to quantify ICI
      related to bowel dysfunction. Educational programs can reduce the stigma
      associated with bowel dysfunction. Further research into the intricate
      relationships between bowel problems, barriers to participation in the community,
      and life satisfaction is needed.

PMID- 17536297
TI  - Physiologic basis of digital-rectal stimulation for bowel evacuation in patients
      with spinal cord injury: identification of an anorectal excitatory reflex.
AB  - BACKGROUND AND PURPOSE: Although advances in rehabilitation practices,
      pharmacology, and surgery offer new bowel program alternatives, digital-rectal
      stimulation is still utilized to facilitate defecation in patients with spinal
      cord injury (SCI). We speculated that defecation induced by such a technique is
      mediated through a reflex mechanism. METHODS: The study comprised 18 healthy
      volunteers (10 men, 8 women, mean age 36.6 +/- 9.7 years) and 9 patients with SCI
      (6 men, 3 women, mean age 35.1 +/- 11.2 years). The anal canal was dilated by a
      balloon inflated in 2-mL increments to 10 mL, and rectal pressure response was
      then recorded. The test was repeated after separate block of the external and
      internal anal sphincters and after individual anesthetization of the anal canal
      and rectum. RESULTS: In normal subjects, the rectal pressure rose significantly
      (p < 0.01) with 2-mL inflation. Increases in anal dilatation effected further
      rectal pressure elevations (p < 0.001), although there were no significant
      differences among the 4-, 6-, and 10-mL distensions (p > 0.05). The rectal
      pressure rise occurred with external, but not with internal, sphincter paralysis.
      In the subjects with paraplegia, there was no rectal pressure response to the 2-
      and 4-mL anal dilatations, while the 6-, 8-, and 10-mL distensions effected
      significant pressure increases (p < 0.001, p < 0.001, p < 0.001, respectively)
      that did not differ significantly among the 3 distending volumes. Internal
      sphincter inhibition, in contrast to the external sphincter, produced no rectal
      pressure response. In both normal subjects and subjects with paraplegia, the
      rectal pressure response did not occur after individual anesthetization of the
      rectum and anal canal. CONCLUSIONS: Anal dilatation induces rectal contraction
      through stimulation of mechanoreceptors, possibly in the internal sphincter.
      Rectal contraction upon anal dilatation suggests a reflex relationship that was
      absent on individual anesthetization of the possible 2 arms of the reflex arc:
      anal canal and rectum. This relationship, which we term the "anorectal excitatory
      reflex," appears to be evoked on digital anal dilatation. The reflex might be of
      diagnostic significance in defecation disorders and has the potential to be used
      as an investigative tool.

PMID- 17536298
TI  - The reproducibility of urodynamic studies of neurogenic bladders in spinal cord
      injury.
AB  - OBJECTIVE: To evaluate the reproducibility (test-retest reliability) of
      urodynamic studies in neurogenic bladders of subjects with spinal cord injuries
      (SCI). DESIGN: Retrospective case series. SETTING: Urology department of a major
      rehabilitation center. SUBJECTS: Fifty individuals with SCI who had urodynamic
      studies performed from February 2000 to April 2000. MAIN OUTCOME MEASURES: Two
      trials (Time 1 and Time 2) of urodynamic studies done 5 minutes apart, with the
      following collected: bladder volume at first sensation, maximum cystometric
      capacity, presence of uninhibited contractions, opening pressure, maximum
      detrusor pressure, duration of bladder contraction, volume voided, and post-void
      residual (PVR) volume. The corresponding data were then compared. Statistical
      analysis was performed using the Lin's concordance correlation coefficient and
      kappa. RESULTS: Analysis of the data showed statistically significant levels of
      agreement between Time 1 and Time 2 with regard to the various corresponding
      parameters for both the filling and voiding phases. For 3 of the most important
      parameters-the opening pressure, maximum detrusor pressure, and duration of
      contraction-the Lin's concordance correlation coefficient (r(c)) was .86 (95% CI,
      .78-.95; p < .0005), .91 (95% CI, .86-.96; p < .0005), and .97 (95% CI, .95-.99,
      p < .0005), respectively. CONCLUSION: The study demonstrates good short-term
      intrasubject reproducibility of urodynamic studies in individuals with SCI.

PMID- 17536299
TI  - The ankle brachial index in chronic spinal cord injury: a pilot study.
AB  - BACKGROUND: Recent case reports implicate peripheral vascular disease (PVD) as an
      etiology for pressure ulcers (PU), failed myocutaneous flap surgeries, and
      amputation in spinal cord injury (SCI). Early detection of PVD is complicated by
      motor and sensory deficits in this population. The ankle-brachial index (ABI) is
      used to quantify PVD in the able-bodied population. We hypothesized that the ABI
      would be a useful screening tool for detecting PVD in patients with SCI.
      Differences in baseline blood pressure, as well as motor and sympathetic
      function, could potentially alter ABI, so values were studied in a sample of
      patients with SCI without risk factors or signs of PVD, and compared to those in
      able-bodied controls without PVD. METHODS: ABI values were measured in 15 healthy
      individuals with chronic complete SCI above the T6 level, who had no evidence for
      risk factors or physical findings of PVD, and compared with the values for a
      group of 10 able-bodied controls. RESULTS: No statistically significant
      difference in ABI was found between patients with SCI and the able-bodied
      comparison group. There was no statistically significant correlation between ABI
      and post-injury duration or incidence of PU. CONCLUSION: ABI may prove to be a
      useful screening device in individuals with SCI. Follow-up studies are needed to
      confirm these findings and to ascertain that the ABI correlates with presence and
      severity of PVD in patients with SCI who have risk factors and signs of PVD.

PMID- 17536300
TI  - Outcomes following traumatic spinal cord injury: clinical practice guidelines for
      health-care professionals.

PMID- 17536301
TI  - Bone marrow metastases: a survey of nonhematologic metastases with
      immunohistochemical study of metastatic carcinomas.
AB  - With current therapies and imaging methods, staging bone marrow biopsies, and
      subsequently found metastases to the bone marrow, are less frequent.
      Historically, the most common metastatic nonhematologic tumors to the bone marrow
      in adult and pediatric patients included breast carcinoma, neuroblastoma,
      prostatic carcinoma, Ewing sarcoma, and lung tumors. Although the staining
      patterns of these primary tumors have been extensively examined, the utility of
      these immunohistochemical profiles has not been studied in the context of
      metastatic lesions to the bone marrow. In our review of 111 metastases to the
      bone marrow over an 18-year period, the most common primary tumor types are, in
      order of frequency: breast carcinoma, neuroblastoma, lung tumors,
      rhabdomyosarcoma, Ewing sarcoma, prostate carcinoma, and gastrointestinal tract
      tumors. Additionally, in an analysis of 44 adult metastatic carcinomas, we
      confirm that immunohistochemical panels are useful in identifying the primary
      tumor site. Overall, the immunohistochemical characterization of metastatic
      carcinomas to the bone marrow show good correlation with the established staining
      pattern of the primary tumors.

PMID- 17536302
TI  - Small cell carcinoma of the urinary bladder--histogenesis, genetics, diagnosis,
      biomarkers, treatment, and prognosis.
AB  - Small cell carcinoma of the urinary bladder is a rare but highly aggressive
      malignancy with a dismal prognosis. Most patients present with advanced disease
      at the time of diagnosis. Hematuria is the most frequent presenting symptom.
      Histologically, small cell carcinoma of the urinary bladder is indistinguishable
      from its pulmonary counterpart. Coexistence with other types of carcinoma is
      common. Histogenesis is uncertain; there are several competing theories,
      including origin from stem cells, from urothelial cells, and from neuroendocrine
      cells in normal or metaplastic urothelium. The molecular pathogenesis remains
      unclear. Immunohistochemical staining can be extremely helpful in establishing
      the diagnosis, and in investigating the use of potential therapeutic strategies.
      Currently, combinations of surgical resection, chemotherapy, and radiation
      therapy represent the main treatment options. The recent observation of c-kit and
      epidermal growth factor receptor expression in more than 25% of patients with
      urinary bladder small cell carcinoma opens new avenues for further investigation.
      Improvement in survival may depend upon the identification of new molecular
      markers to facilitate earlier diagnosis and the development of novel targeted
      therapies. In this paper, we review general aspects of small cell carcinoma of
      the urinary bladder, focusing on the ways in which our understanding of this
      entity has been positively influenced by studies of the histopathologic and
      immunohistochemical findings, and by investigations of genetic alterations in
      this disease.

PMID- 17536303
TI  - Immunophenotypic profiling of nonsmall cell lung cancer progression using the
      tissue microarray approach.
AB  - This study, using tissue microarrays, aimed at the immunomorphologic profiling of
      nonsmall cell lung cancer (NSCLC) cases to reveal clinically relevant disease
      groups and biomarkers associated with patients' survival and tumor progression
      including brain metastatic potential. Donor tissue blocks were form 59 patients,
      including 33 primary tumors without distant metastasis and 26 brain metastatic
      primary tumors as well as the brain metastases. Sections were immunostained for
      29 markers targeting molecules of cell adhesion, cell growth, cell cycle, and
      apoptosis regulation. beta-Catenin expression was the only independent prognostic
      marker associated with better outcome. Elevated expression of collagen XVII,
      CD44v6, and caspase-9, and the reduced production of beta-catenin and cellular
      apoptosis susceptibility protein were significantly associated with the
      metastatic potential of primary NSCLC. Expression of positive cell cycle
      regulators cyclin D1 and cyclin D3 was also increased in metastatic primary
      tumors. Metastatic tumor progression into the brain was accompanied by prominent
      p16, syndecan-1, p53 (DO7), and caspase-3 protein levels. Hierarchical clustering
      of complex immunoprofiles based on the differentially expressed markers grouped
      NSCLCs of the poorest outcome with high correlation including 2/3 of brain
      metastases of mixed histology. The brain metastatic potential of NSCLCs may be
      linked to the elevated levels of cyclinD1, cyclinD3, p16, p53, caspase-3, caspase
      9, CD44v6, and collagen XVII and the down-regulation of beta-catenin and cellular
      apoptosis susceptibility protein. Unsupervised immunoprofiles based on
      differentially expressed biomarkers may help selecting lung cancers with
      aggressive behavior.

PMID- 17536304
TI  - Survivin expression in non-small-cell lung carcinomas: correlation with apoptosis
      and other apoptosis-related proteins, clinicopathologic prognostic factors and
      prognosis.
AB  - The role of survivin that regulates the biological behavior of non-small-cell
      lung carcinoma (NSCLC) is still controversial. We aimed to investigate survivin
      expression in NSCLC and to define any correlation with expressions of p53, bcl-2,
      bax, apoptotic index (AI), tumor cell proliferation, clinicopathologic variables,
      and overall survival. Tumors of 63 patients with NSCLC were examined for
      expressions of survivin, p53, bcl-2, bax, and Ki-67 by immunohistochemistry. AI
      was also evaluated. Results for each antibody were correlated with each other,
      and with clinicopathologic variables including age, sex, histologic subtype, TNM
      (T: primary tumor, N: regional lymph node metastasis, M: distant metastasis)
      stage, lymph node status, smoking history, and prognosis. Nuclear survivin
      expression was inversely correlated with p53 expression (P = 0.04, r = - 0.367),
      and tumor stage (P = 0.03, r = - 0.273), and positively correlated with tumor
      cell proliferation (P = 0.009, r = 0.329). Cytoplasmic survivin expression
      positively correlated with smoking history (P = 0.02, r = 0.282). Survivin/bax
      ratio was inversely correlated with AI (r: - 0.004). By Kaplan-Meier analysis,
      TNM stage (P < or = 0.001), lymph node metastasis (P = 0.04), and Ki-67 index (P
      < or = 0.001) were associated with survival, whereas survivin was not. In
      multivariate analysis, only TNM stage was an independent predictor. Although
      survivin and other apoptosis-related protein expressions fail to predict the
      clinical outcome, the present findings suggest that survivin is involved in tumor
      cell apoptosis and proliferation and may play a role in critical steps of cancer
      progression in NSCLC.

PMID- 17536305
TI  - Extranodal NK/T-cell lymphoma, nasal type: study of clinicopathologic and
      prognosis factors in a series of 78 cases from Peru.
AB  - It is well known that extranodal NK/T-cell lymphoma (NK/TCL) nasal type clusters
      in Asian countries. A large series of 78 cases of nasal NK/TCL from Peru is
      analyzed in the present study. Two histologic groups 1 (monomorphic) and 2
      (polymorphic), were segregated according to the proportion of large cells (above
      and below 30%, respectively). Catalyzed signal amplification technique was
      performed for enhancement of immunohistochemistry reactivities. Epstein-Barr
      virus (EBV) sequences and types were investigated using polymerase chain
      reaction. Clinical characteristics, stage, outcome, and response to treatment
      were evaluated in both groups. Fourteen cases (18%) and 64 cases (82%)
      corresponded to groups 1 and 2, respectively. Except for nasal obstruction, more
      common in group 2, all other symptoms were similar in both groups. Local
      extension and staging were also comparable. Both groups showed CD3c+ CD2+ CD56+
      CD3s- CD20- immunophenotype. All cases were positive for EBV. In this series type
      2 EBV was found more frequent than type-1 EBV, contrarily to that observed in
      Asian series. However, about one-third of cases simultaneously harbored both
      viral types. Both groups received an average of 50-Gy dose of radiation therapy
      (RT), with or without chemotherapy. Complete therapeutic response was achieved in
      89% of group 1 and in 74% of group 2, but this difference was not statistically
      significant. There were no significant differences between the groups regarding
      disease-free survival, failure-free survival, relapse, and overall survival. The
      overall survival, in both groups, was longer for patients treated with RT alone
      compared with those treated with combined RT therapy and chemotherapy. The
      present study has shown that dividing nasal NK/TCL in monomorphic and polymorphic
      variants, according to frequency of large cells, does not correlate with clinical
      and prognostic factors.

PMID- 17536306
TI  - Clinical validation of breast cancer biomarkers using tissue microarray
      technology.
AB  - The results of previous studies done in our laboratory on breast cancer gene
      expression profile, using DNA microarrays, led to the discovery of several genes
      associated with breast cancer progression. Further evaluation of these genes and
      their involvement at various stages of cancer progression required performance of
      immunohistochemistry on thousands of different tissue blocks. Tissue microarray
      (TMA) technology facilitates rapid translation of DNA microarrays results to
      clinical specimens by using immunohistochemical analysis of protein expression.
      DNA microarray analysis done in our laboratory showed a significantly higher
      expression of prostatic-specific antigen (PSA) in invasive ductal carcinomas as
      compared to ductal carcinoma in situ, a finding contrary to the previously
      published data for PSA immunoreactivity in breast carcinomas. To find out whether
      TMA strategy could be used to explore the expression of the candidate genes
      involved in the breast cancer progression, we constructed a breast cancer
      progression TMA. It consisted of 2 normal ductal epithelium, 8 ductal carcinoma
      in situ, 19 invasive ductal carcinomas, and 3 metastatic ductal carcinomas of
      breast in triplets. Two prostatic adenocarcinomas and 2 normal colons were used
      as positive and negative controls, respectively. We first used well-documented
      and well-tested markers, such as antibodies to estrogen receptor, progesterone
      receptor, and p53. Results of these 3 antibodies were according to the previously
      published data. To validate our result, we then used antibody to PSA and looked
      for the expression of this protein on breast cancer progression TMA. Except for
      the 2 positive controls all 98 cores were found to be negative for PSA expression
      highlighting the importance of validation studies for DNA microarray results.

PMID- 17536307
TI  - The 3-dimensional structure of isolated and small foci of prostatic
      adenocarcinoma: the morphologic relationship between prostatic adenocarcinoma and
      prostatic intraepithelial neoplasia.
AB  - BACKGROUND: Transitional histopathologic changes from high-grade prostatic
      intraepithelial neoplasia (HGPIN) into early prostatic adenocarcinoma (PAC) have
      not been well studied to date. To investigate the histogenesis of PAC, we
      examined isolated and small foci of PAC (ISPAC) found in prostatectomy specimens
      and the 3-dimensional structure of these foci. DESIGN: Twelve consecutive radical
      prostatectomy specimens having ISPAC, performed for peripheral zone PAC (10
      cases) and for transitional zone PAC (2 cases), of Gleason score were studied.
      One to 2 tissue blocks with representative sections were used. RESULTS: Eight
      ISPAC, with Gleason score 3 + 3 had complete serial sections of the entire
      lesion. PAC consisted of continuous, tortuous and branching tubules and acini
      arising from benign ducts displaying: (a) HGPIN in 5 ISPAC and (b) no HGPIN in 3
      ISAPC. At the junctions between benign epithelia with or without HGPIN and
      malignant epithelia, there were transitional lesions with HGPIN involving small
      ducts and acini. CONCLUSIONS: PAC develops as a result of multiple outpouchings
      of the epithelium with formation of small ducts and acini showing cytologic
      atypia and gradual or abrupt loss of basal cells. Grade 3 ISPAC consists of a
      system of continuous duct pushing into the stroma. There is also evidence
      suggestive of HGPIN as being both a precursor lesion and an accompanying lesion
      of PAC.

PMID- 17536308
TI  - HER-2/neu expression in glioblastoma multiforme.
AB  - BACKGROUND: The HER-2/neu oncogene encodes for a transmembrane glycoprotein with
      intracellular tyrosine kinase activity. The HER-2/neu receptor belongs to the
      family of epidermal growth factor receptors that are crucial in the activation of
      subcellular signal transduction pathways controlling epithelial cell growth and
      differentiation. Overexpression of HER-2/neu is observed in 20% to 40% of breast
      cancers and other solid tumors. Although information is limited, one study
      suggested that 15% of glioblastoma multiforme (GBM) express HER-2/neu by
      immunohistochemistry (IHC); gene amplification by fluorescence in situ
      hybridization (FISH) was not investigated. Studies in this area are potentially
      significant owing to the role of recombinant monoclonal anti-HER-2/neu antibody
      traztuzumab (Herceptin) in the treatment of tumors. DESIGN: A retrospective
      clinicopathologic review of 49 patients with GBM with HER-2/neu IHC staining and
      HER-2/neu gene amplification by FISH was performed. RESULTS: The study included
      44 patients (17 women, 27 men; age range 20 to 79 y, mean 57.9 y). Initial
      surgery involved tumor debulking or subtotal resection in 34 patients. Thirty-six
      patients received adjuvant radiation therapy and 19 patients received adjuvant
      chemotherapy. At follow-up (range 1.0 to 49.5 mo, mean 10.5 mo), 40 patients died
      with tumor and 4 patients were lost to follow-up. All tumors were negative for
      HER-2/neu protein by IHC and for HER-2/neu gene amplification by FISH.
      CONCLUSIONS: No GBM demonstrates HER-2/neu protein by IHC or amplification of the
      HER-2/neu gene by FISH. The HER-2/neu oncogene does not seem to play a role in
      the pathogenesis of GBM.

PMID- 17536309
TI  - Maspin is useful in the distinction of pancreatic adenocarcinoma from chronic
      pancreatitis: a tissue microarray based study.
AB  - Maspin, a member of the serpin family of serine protease inhibitors, has been
      shown to limit invasion and metastases in breast and prostate carcinomas. Maspin
      gene expression is up-regulated in pancreatic cancer, but not in normal
      pancreatic tissue. Maspin expression has been documented using
      immunohistochemical studies in pancreatic adenocarcinoma and high-grade
      intraductal dysplasia. We studied pancreatic ductal adenocarcinomas and chronic
      pancreatitis utilizing tissue microarray technology to determine the utility of
      maspin in differentiating these lesions. Immunohistochemistry was performed on
      tissue microarrays made from 72 cases of pancreatic ductal adenocarcinoma and 24
      cases of chronic pancreatitis. Carcinomas were graded as well, moderately, or
      poorly differentiated using the WHO criteria. The primary antibody used was
      monoclonal antimaspin antibody (clone G167-70, 1:800, PharMingen, San Diego, CA).
      Nuclear and/or cytoplasmic staining for maspin was qualitatively scored from 1 +
      to 3 + based on intensity. Cases were considered positive if one or more cores
      demonstrated staining. Cases of chronic pancreatitis showed focal, weak (1 + to 2
      +) staining within occasional benign ductal epithelial cells in 29% of cases
      (7/24). Diffuse and intense (3 +) staining was present in ducts with squamous
      metaplasia (3 cases). The majority of ducts showed no staining. Ductal
      adenocarcinomas showed diffuse staining in 91% (66/72) of cases with generally
      more intense staining than cases of chronic pancreatitis. Maspin may be helpful
      in differentiating ductal adenocarcinoma from chronic pancreatitis, once squamous
      metaplasia is ruled out.

PMID- 17536310
TI  - Immunoreactivity of p53, Mdm2, p21(WAF1/CIP1) Bcl-2, and Bax in soft tissue
      sarcomas: correlation with histologic grade.
AB  - Tumor growth depends on 2 distinctive pathways: cell proliferation and apoptosis.
      The p53 pathway is an important regulator of the cell cycle as it triggers growth
      arrest or leads to apoptosis in response to cellular stress and therefore is
      commonly targeted during tumorigenesis. Apoptosis is also controlled by the Bcl-2
      family, which includes proapoptotic and antiapoptotic proteins. The aim of this
      study was to investigate the expression of proteins that are involved in the p53
      pathway and apoptosis in different types of soft tissue sarcomas and to correlate
      the expression of these proteins with the histologic grade of sarcoma cases. One
      hundred fifty-two cases of different types of soft tissue sarcomas were analyzed.
      The cases consisted of 54 low-grade, 40 intermediate-grade, and 58 high-grade
      sarcomas. Immunohistochemical stains for p21(WAF1/CIP1), p53, Mdm2, Bcl-2, and
      Bax proteins were carried out on tissue microarrays. Nuclear reactivity for p53
      was detected in 49 cases (32.2%). Overexpression of Mdm2 was found in 18 cases
      (11.8%) and p21(WAF1/CIP1) immunostaining was seen in 28 tumors (18.4%). p53 and
      p21(WAF1/CIP1) expression correlated with the tumor grade (low grade, 5.6% and
      3.7%; intermediate grade, 22.5% and 20%; high grade, 63.8% and 31%,
      respectively). Expression of Bax protein was a common finding in soft tissue
      sarcoma cases. It was detected in 141 cases (92.8%). Bcl-2 was identified in 59
      tumors (38.8%) and was more prevalent in high-grade sarcomas (low grade, 25.9%;
      intermediate grade, 32.5%; high grade, 55.2%). It was concluded that alterations
      in the p53 pathway and genes that regulate apoptosis are common events in soft
      tissue sarcomas. The expression of p53, p21(WAF1/CIP1), and Bcl-2 is closely
      associated with the histologic grade of the tumor, and therefore these proteins
      may be used as prognostic markers.

PMID- 17536311
TI  - Expression of cyclooxygenase-2 in osteosarcoma of bone.
AB  - Several studies indicate that cyclooxygenase-2 (COX-2) is overexpressed in human
      malignancies, where it produces high levels of prostaglandins and contributes to
      tumor growth. In this study we have analyzed the expression of COX-2 in a series
      of 48 skeletal osteosarcomas of different subtypes by immunohistochemistry. In
      addition, we examined the effects of the specific COX-2 inhibitor Celecoxib on
      the growth of the human osteosarcoma cell line SaOS-2. Immunoreactivity for COX-2
      was observed in 39 out of 48 tumors (81.2%), 30 (76.9%) of which showed a
      moderate or diffuse immunostaining. Considering the group of 42 primary
      osteosarcomas, COX-2 immunoreactivity was significantly higher in high grade
      osteosarcomas, where moderate or diffuse expression was detected in 23 out of 32
      cases (71.8%), than in low grade osteosarcomas, where moderate or diffuse
      expression was detected in 2 out of 10 cases (20%) (P = 0.008, Fisher exact
      test). In addition, low COX-2 expression was always associated with a good
      response to chemotherapy (5 out of 5 cases), whereas moderate or diffuse COX-2
      expression was associated with a good response in 11 out of 20 cases (55%) (P =
      0.12, Fisher exact test). In SaOS-2 osteosarcoma cells, which express COX-2,
      treatment with Celecoxib determined inhibition of cell proliferation and
      induction of apoptosis. These results indicate that COX-2 is expressed at high
      levels in high grade osteosarcomas and support the use of COX-2 inhibitors to
      improve both the tumor response to chemotherapy and the outcome of osteosarcoma
      patients.

PMID- 17536312
TI  - NY-BR-1 is a differentiation antigen of the mammary gland.
AB  - NY-BR-1 was recently identified by autologous serological typing of the
      recombinant expression library in a breast cancer patient. Extensive reverse
      transcriptase-polymerase chain reaction analysis revealed the presence of NY-BR-1
      in normal breast tissue and tumors derived thereof. Except normal testis, no
      other normal tissue or tumors showed NY-BR-1 expression. However, nothing is
      known about the expression of its actual antigen. In the present study, we
      describe the generation of 2 new monoclonal antibodies, NY-BR-1#2 and NY-BR-1#3,
      to NY-BR-1 for the analysis of its expression on a protein level employing
      recombinant NY-BR-1 protein for the immunization of BALB/c mice. In normal
      tissues, immunohistochemical testing demonstrates NY-BR-1 in a mostly focal
      fashion in the epithelia of ducts and acini of the mammary gland. No other tissue
      was immunopositive including testis. In tumors, homogenous staining can be seen
      in almost all ductal carcinomas in situ and/or the intraductal component of
      invasive carcinomas. Invasive carcinomas show a lower number of NY-BR-1-positive
      tumors. Initial higher numbers of NY-BR-1 mRNA-positive invasive carcinomas are
      most likely based on sample error owing to the contamination of tumor tissue with
      remnants of normal breast epithelium. Sweat gland carcinomas, which are related
      to breast cancer, are also positive in about one-third of the cases. These data
      indicate that NY-BR-1 is a differentiation antigen of the mammary gland that
      could be useful for diagnosis and/or immunotherapy of breast carcinomas.

PMID- 17536313
TI  - Effects of fixative and fixation protocols on assessment of Her-2/neu oncogene
      amplification status by fluorescence in situ hybridization.
AB  - Fluorescence in situ hybridization (FISH) is used to determine amplification
      status of the Her-2/neu gene in specimens of newly diagnosed breast carcinoma.
      The Vysis kit for FISH analysis stipulates that the tissue be formalin-fixed and
      paraffin-embedded. Concerns regarding carcinogenicity of formalin and
      environmental effects of formalin waste have led to the development of formalin
      replacement products. An increasing number of breast biopsy specimens are being
      fixed in these substitutes. We tested 6 non-formalin-based fixatives to determine
      their impact on FISH testing for Her-2/neu gene amplification status by
      comparison with formalin-fixed control specimens from the same neoplasm.
      Specimens fixed in Pen-Fix, Prefer, Histochoice, UniFix, and GTF were associated
      with absent or technically compromised staining in at least one of the 3
      neoplasms tested for each fixative when compared to the formalin-fixed control. O
      Fix did not seem to compromise staining quality in 3 paired specimens tested.

PMID- 17536314
TI  - Microwave enhancement of CISH for HER2 oncogene.
AB  - We describe a modification to the prescribed procedure for the Zymed Spot-Light
      HER2 chromogenic in situ hybridization kit (84-0146, Zymed Laboratories, San
      Francisco, CA) by substituting the heat pretreatment step with MW irradiation in
      citrate buffer 10 mmol/L at pH 6.0 at 98 degrees C for 10 minutes and repeating
      the procedure afterenzyme digestion with time and temperature controlled in the
      Mega T/ T oven (Milestone s.r.l., Sorisole, Italy). The subsequent procedure
      leading up to hybridized was as per manufacturer's instructions. Invasive breast
      carcinoma previously scored by immunohistochemistry for HER2, comprising 18 cases
      of 3+, 18 cases of 2+, and 12 cases of 1+, were examined by chromogenic in situ
      hybridization using this modified procedure, with a parallel set of cases
      examined by the prescribed Zymed method. The introduction of the "MW retrieval"
      steps resulted in consistently a greater number of hybridization signals in
      amplified tumor cells with benign epithelial cells and lymphocytes displaying 2
      clear dots compared with the weaker and less consistent signals obtained with the
      standard procedure. MW exposed sections showed larger numbers of large and small
      clusters that often allowed identification of amplified tumors without having to
      count single dots with crisp staining and absence of background precipitation.

PMID- 17536315
TI  - A new rabbit monoclonal antibody (4B5) for the immunohistochemical (IHC)
      determination of the HER2 status in breast cancer: comparison with CB11,
      fluorescence in situ hybridization (FISH), and interlaboratory reproducibility.
AB  - The 2 methodologies in current clinical use to assess HER2 status in breast
      cancer are: fluorescence in situ hybridization (FISH) (gene amplification) and
      immunohistochemistry (protein over-expression). A consistent finding has been
      that 3% to 15% of breast cancers over-express HER2 protein without evidence for
      gene amplification. Accurate determination of the HER2 status has implications
      for selecting patients most likely to respond to trastuzumab. We report here our
      preliminary experience with a new anti-HER2 rabbit monoclonal antibody, 4B5. The
      evaluation of HER2 status in 2 different cohorts of breast cancer cases (Single
      Institution (SI) and Multinational (MN)) with a total of 322 breast cancer cases
      was performed on an automated staining system (Ventana Medical Systems, Inc,
      Tucson, AZ) and scored by 3 pathologists (0-3+), for comparison with CB11
      staining results (PATHWAY) and FISH (PathVysion). Interlaboratory reproducibility
      of automated staining results and interpretation was determined on a subset of
      the SI cohort at 3 separate laboratories. Rabbit monoclonal 4B5 demonstrated
      sharper membrane staining with less cytoplasmic and stromal background staining
      than CB11. In the SI cohort, the staining results for 4B5 were highly comparable
      with those obtained for CB11 with an overall concordance of 93.3%. In the
      multinational cohort, the overall concordance with CB11 was 84.7%. This lower
      level of concordance was associated with a much higher overall agreement of 4B5
      with FISH (89.5%), compared with agreement of CB11 with FISH (81.2%). The
      difference in the performance of CB11 in the MN cohort versus the SI cohort may
      be due to differences in tissue fixation and processing in a centralized, high
      volume laboratory in an academic medical center versus multiple sites in the
      international community with potentially nonstandardized techniques. The staining
      results with 4B5 indicate that it has a more robust performance than CB11 because
      the correlation of 4B5 with FISH was nearly equivalent (88.2% MN; 89.3% SI) in
      both cohorts. Interlaboratory reproducibility was also excellent (kappa 1.0).
      RMoAb 4B5 provides excellent sensitivity, specificity, and interlaboratory
      reproducibility for the detection of HER2 status in breast cancer.

PMID- 17536316
TI  - Background staining of visualization systems in immunohistochemistry: comparison
      of the Avidin-Biotin Complex system and the EnVision+ system.
AB  - The aim of this study was to evaluate specific immunostaining and background
      staining in formalin-fixed, paraffin-embedded human tissues with the 2 most
      frequently used immunohistochemical detection systems, Avidin-Biotin-Peroxidase
      (ABC) and EnVision+. A series of fixed tissues, including breast, colon, kidney,
      larynx, liver, lung, ovary, pancreas, prostate, stomach, and tonsil, was used in
      the study. Three monoclonal antibodies, 1 against a nuclear antigen (Ki-67), 1
      against a cytoplasmic antigen (cytokeratin), and 1 against a cytoplasmic and
      membrane-associated antigen and a polyclonal antibody against a nuclear and
      cytoplasmic antigen (S-100) were selected for these studies. When the ABC system
      was applied, immunostaining was performed with and without blocking of endogenous
      avidin-binding activity. The intensity of specific immunostaining and the
      percentage of stained cells were comparable for the 2 detection systems. The use
      of ABC caused widespread cytoplasmic and rare nuclear background staining in a
      variety of normal and tumor cells. A very strong background staining was observed
      in colon, gastric mucosa, liver, and kidney. Blocking avidin-binding capacity
      reduced background staining, but complete blocking was difficult to attain. With
      the EnVision+ system no background staining occurred. Given the efficiency of the
      detection, equal for both systems or higher with EnVision+, and the significant
      background problem with ABC, we advocate the routine use of the EnVision+ system.

PMID- 17536317
TI  - Radiographic determination of tissue thickness in paraffin blocks: application to
      the construction of tissue microarrays.
AB  - The determination of tissue thickness in paraffin blocks in the histology
      laboratory has been largely based on visual estimates. More accurate methods are
      required for the construction of tissue microarrays (TMAs) to assure a greater
      yield of cores in sections through the TMA block. We describe an accurate
      radiographic method to determine tissue thickness in donor paraffin blocks and
      have validated its application to TMA construction. Individual radiographic
      analysis was performed on paraffin donor blocks used for the construction of TMAs
      for determination of donor block tissue thickness. Consecutive numbered slide
      sections through the TMA block were then examined for the presence or loss of
      cores in the 150th TMA slide (from the final third of the TMA block) and
      correlated with the thickness of the individual donor blocks determined
      radiographically. At the 150th TMA slide, 202 of 1340 cores (15.1%) were
      depleted. Radiographic measurement showed a greater thickness of the donor
      paraffin block tissue (2.02 mm) corresponding to the retained cores as compared
      with the donor tissue (1.54 mm) of the depleted cores (P < 0.001). With
      progressive slide sections through a TMA block, the retention of tissue cores
      shows a significant correlation with donor block tissue thickness. Radiographic
      determination of tissue thickness in donor paraffin blocks can be used in TMA
      construction. Prior knowledge of tissue thickness in TMA construction can prompt
      compensatory steps that can enhance the yield of valuable samples and assure
      sufficient numbers of adequate cores for statistical analysis in biomarker
      evaluations.

PMID- 17536319
TI  - Time 100 heroes & pioneers. Elizabeth Edwards.

PMID- 17536318
TI  - Comparing vasculogenic mimicry with endothelial cell-lined vessels: techniques
      for 3D reconstruction and quantitative analysis of tissue components from
      archival paraffin blocks.
AB  - We previously described techniques to generate 3-dimensional reconstructions of
      the tumor microcirculation using immunofluorescence histochemistry and laser
      scanning confocal microscopy on serial sections from archival formalin-fixed,
      paraffin-embedded tissues. By aligning sequential z-stacks in an immersive
      visualization environment (ImmersaDesk), the need to insert fiduciary markers
      into tissue was eliminated. In this study, we developed methods to stitch
      overlapping confocal z-series together to extend the surface area of interest
      well beyond that captured by the confocal microscope objective and developed
      methods to quantify the distribution of markers of interest in 3 dimensions.
      These techniques were applied to the problem of comparing the surface area of
      nonendothelial cell-lined, laminin-rich looping vasculogenic mimicry (VM)
      patterns that are known to transmit fluid, with the surface area of endothelial
      cell-lined vessels in metastatic uveal melanoma to the liver in 3 dimensions.
      After labeling sections with antibodies to CD34 and laminin, the surface area of
      VM patterns to vessels was calculated by segmenting out structures that labeled
      with laminin but not with CD34 from those structures labeling with CD34, or CD34
      and laminin. In metastatic uveal melanoma tissues featuring colocalization of
      high microvascular density [66.4 microvessels adjusted for 0.313 mm2 area (range
      56.7 to 72.7)] and VM patterning, the surface area of VM patterns was 11.6-fold
      greater (range 10.8 to 14.1) than the surface provided by CD34-positive vessels.
      These methods may be extended to visualize and quantify molecular markers in 3
      dimensions in a variety of pathologic entities from archival paraffin-embedded
      tissues.

PMID- 17536320
TI  - Time 100 scientists & thinkers. Craig Venter.

PMID- 17536321
TI  - Time 100 scientists & thinkers. Richard Dawkins.

PMID- 17536322
TI  - Time 100 scientists & thinkers. Nora Volkow.

PMID- 17536323
TI  - Time 100 scientists & thinkers. Al Gore.

PMID- 17536324
TI  - Time 100 scientists & thinkers. Frans de Waal.

PMID- 17536325
TI  - Time 100 scientists & thinkers. Elizabeth Blackburn.

PMID- 17536326
TI  - Time 100 scientists & thinkers. Svante Paabo.

PMID- 17536327
TI  - Time 100 scientists & thinkers. Douglas Melton.

PMID- 17536328
TI  - Change. What is our response?

PMID- 17536329
TI  - A nurse's guide to common mechanical ventilation techniques and modes used in
      infants. Nursing implications.
AB  - The need for conventional mechanical ventilation (CMV) is a common one in the
      neonatal intensive care unit (NICU). The goals of CMV are to facilitate adequate
      gas exchange, minimize the risk of lung injury/damage, decrease the patient's
      work of breathing, and optimize the patient's comfort. Although time-cycled,
      pressure-limited ventilation remains the most common CMV modality, volume-cycled
      ventilation, assist-control ventilation, pressure-support ventilation, and
      pressure-control ventilation are sometimes used in the NICU. Pressure-regulated
      volume control, volume-guaranteed ventilation, volume-assured pressure-support
      ventilation, and proportional-assist ventilation are emerging hybrid modes of
      CMV. Although CMV is frequently life saving, it can cause complications if
      improperly used. Nurses are responsible for the ongoing assessment and care of
      infants undergoing CMV and are becoming frequently more involved in the weaning
      process of CMV. This article provides an overview of conventional ventilation,
      with a focus on common modalities, and ventilation-related nursing interventions.

PMID- 17536330
TI  - Neonatal peripherally inserted central catheter team. Evolution and outcomes of a
      bedside-nurse-designed program.
AB  - Percutaneously inserted central venous catheters (PICCs) have been used to
      provide central venous access for more than 25 years. Although these lines
      initially were placed by physicians, currently there are many adult, pediatric,
      and neonatal nurse-based PICC teams. This article describes the inception and
      growth of 1 team which, during the last 14 years, has placed more than 3400
      catheters and trained more than 50 bedside nurses to insert PICCs. It highlights
      the development of the team, including details of how team members were selected
      and trained. Management of ongoing issues was handled by a self-directed nurse
      team organized into a committee structure composed of an oversight committee and
      education, guideline, qualifications, and quality improvement subcommittees. This
      team set and achieved the goals of training bedside nurses to place PICCs,
      providing consistent management of PICCs, and closely monitoring outcomes.

PMID- 17536331
TI  - Part 3: examination of the newborn with closed spinal dysraphism.
AB  - Spinal dysraphism, an incomplete closure of the neural tube, can be open,
      exposing the neural elements to the environment, or can be closed, covered with
      skin. Abnormal development of the spine occurs early in life and also interferes
      with usual development of the skin. This often creates cutaneous markers or
      stigmata over the area. Cutaneous markers may include a subcutaneous mass,
      abnormal hair growth, skin dimple, tag or sinus, or unusual pigmentation.
      Recognizing these markers is important because, although many closed spinal
      dysraphisms are asymptomatic at birth, neurological sequelae can occur. The
      sequelae are insidious and often permanent. This article, Part 3 in a series of
      articles devoted to spinal assessment, reviews closed spinal dysraphisms. The
      article emphasizes identification of various cutaneous markers associated with
      closed spinal dysraphisms. Early detection and follow-up may prevent neurologic
      sequelae for the infant later in life.

PMID- 17536332
TI  - Testing the satisfaction and feasibility of a computer-based teaching module in
      the neonatal intensive care unit.
AB  - PURPOSE: To examine the satisfaction with and feasibility of a computer-based
      teaching module to teach healthcare professionals how to use and apply the
      Premature Infant Pain Profile (PIPP) to clinical scenarios. SUBJECTS: Sixty-eight
      healthcare professionals who were employed in the neonatal intensive care unit
      (NICU) on a full-time or part-time basis and had received an educational session
      regarding the PIPP. DESIGN AND METHODS: A pilot study using an exploratory
      descriptive design was used to answer: (1) How satisfied are healthcare
      professionals with the computer-based teaching module? and (2) What is the
      feasibility of a computer-based teaching module in the clinical setting?
      Satisfaction was measured using an investigator-developed 5-point Likert scale.
      Feasibility was measured in terms of time to complete the module, satisfaction
      with instructions and ability to navigate through the module, acceptability of
      the module as a teaching method, and format with the computer-based module.
      PRINCIPAL RESULTS: Ninety percent of those sampled were very satisfied with the
      computer-based teaching method. Use of video and audio clips and photographs
      enhanced the learning process. Healthcare professionals identified the computer
      based teaching method as an effective way of learning about the PIPP and thought
      that it was feasible to use within the clinical setting. CONCLUSIONS: Computer
      based teaching is a feasible method for educating NICU healthcare professionals
      about the PIPP. Additional research is required to examine the effectiveness of
      this teaching method on relevant patient outcomes such as pain management.

PMID- 17536333
TI  - Expression, purification and characterization of a synthetic gene encoding human
      amyloid beta (Abeta1-42) in Escherichia coli.
AB  - Alzheimer's disease (AD) is a neurodegenerative disorder characterized by a
      progressive loss of cognitive function. Existing evidence indicates that abnormal
      processing and extracellular deposition of the longer form of the amyloid peptide
      Abeta(1-42), a proteolytic derivative of the amyloid precursor protein (APP), is
      a key step in the pathogenesis of AD. Active immunization with Abeta(1-42) has
      been shown to decrease brain beta deposition and improve cognitive performance in
      mouse models of AD. In the present study, we sought to express the synthetic gene
      encoding AB in Escherichia coli to enable rapid production of the antigen and its
      purification. The synthetic gene has been constructed from six oligonucleotides
      by employing overlapping PCR strategy and expressed in E. coli using the T7
      promoter system. The recombinant peptide has been purified to homogeneity by a
      single step Ni+2 affinity chromatography. Enzyme-linked immunosorbent assay
      (ELISA) using polyclonal anti-Abeta(1-42) sera confirms that the corresponding
      linear B-cell epitopic sequences are available for immunorecognition in the
      recombinant peptide. This methodology enables rapid, continuous production and
      purification in bulk amounts of human Abeta sequence by employing bacterial
      expression system

PMID- 17536334
TI  - Purification and properties of alpha-galactosidase from white-rot fungus
      Pleurotus florida.
AB  - alpha-Galactosidase was strongly induced in the white-rot fungus Pleurotus
      florida by arabinose than its natural substrates and was purified to homogeneity
      by acetone precipitation, ultrafiltration and DEAE-Sepharose chromatography. The
      enzyme was a monomeric protein with a molecular mass of approximately equal to 99
      kDa, as revealed by native-PAGE and SDS-PAGE. alpha-Galactosidase was optimally
      active at 55 degrees C for the hydrolysis of p-nitrophenyl-alpha
      galactopyranoside (PNPalphaG) and lost its 20% and 50% of original activity in 30
      min at 60 degres C and 70 degrees C, respectively. The pH optimum of the enzyme
      was between 4.6 and 5.0. It was stable in a wide pH range (pH 4.0 to 9.0) at 55
      degrees C for 2 h. The Ag+ and Hg2+ strongly inhibited the enzyme activity.
      Galactose, glucose, maltose and lactose also inhibited the enzyme activity,
      whereas N-bromosuccinimide treatment resulted in near total loss of acitivity.
      The Km and Vmax values of the enzyme for PNPalphaG were found to be 1.1 mM, and
      77 micromol min(-1) mg(-1), respectively. alpha-Galactosidase immobilized in agar
      was more effective for the degradation of raffinose than in the sodium alginate.
      TLC results indicated its potential for the removal of raffinose and stachyose in
      soymilk.

PMID- 17536335
TI  - Electrochemical studies of glucose oxidase immobilized on glutathione coated gold
      nanoparticles.
AB  - Glutathione (L-gamma-glutamyl-L-cysteinyl-L-glycine; GSH) forms a surface
      monolayer on gold nanoparticles by tethering via sulfur bonds (Au:GSH). In the
      present study, glucose oxidase (GOx; EC 1.1.3.4) was immobilized by covalent
      chemical coupling reactions on to Au:GSH nanoparticles and the enzyme coupled
      nanoparticles formed a stable colloid (stable for several weeks) in water. The
      immobilized enzyme was investigated for electrochemical characteristics to
      monitor the FAD (prosthetic group of the GOx) redox potentials. Various
      concentrations of substrate (glucose) were added to check the oxidation
      characteristics. It was observed that with increase in substrate concentrations,
      the oxidation rate increased proportionally with the current. The present study
      demonstrated that GOx was effectively coupled to the gold nanoparticle (Au:GSH).
      The coupled nanoparticle system could be used in a potential biosensor
      application. Similarly, other enzymes (e.g., horseradish peroxidase) could be
      immobilized to the Au:GSH nanoparticles via the peptide arm (GSH) to achieve the
      desired characteristics needed for a specific application in biosensor.

PMID- 17536336
TI  - Improved method for estimation of inorganic phosphate: implications for its
      application in enzyme assays.
AB  - The conventional method of Fiske and Subba Row for the estimation of inorganic
      phosphate (Pi) is although rapid, but suffers from the disadvantage that the
      color is unstable and hence the optical density (OD) measurements have to be
      carried out within a short time span of 8-12 min. This poses a restriction on the
      number of samples, which can be handled in a batch. Although, modified procedures
      involving use of alternate reducing agents/or increasing the concentration of
      H2SO4 in conventional method have been subsequently developed, but the problem of
      color stability could not be solved. In addition, the use of higher
      concentrations H2SO4 has rendered the methods unsuitable in enzyme assays,
      especially if the acid labile phosphate containing substrates have been used. In
      the present study, attempts have been made to suitably modify the method to
      improve the stability of the color and sensitivity and also for its applicability
      in enzyme assays, especially when acid labile phosphate containing substrates
      such as ATP is used. We used the higher concentrations (0.625, 0.8 and 1.0 N) of
      H2SO4 rather than 0.5 N used in the conventional assay procedures. Under these
      conditions, the reagent blanks do not develop color for up to 24 h, whereas the
      intensity of the molybdenum blue color in the standard and/or experimental tubes
      increased with time reaching optimum value at 24 h. Simultaneously, the
      absorption maximum shifts from 660 nm to 820 nm. The highest concentration of
      H2SO4 (1.0 N) is found to be the most effective in the process of color
      development. The sensitivity of the method is from 1.7 to 2.1 times higher, as
      compared to the conventional Fiske and Subba Row method for the measurements
      carried out at the end of 15 min at 820 nm and with the highest concentration of
      H2SO4 (1.0 N); the sensitivity increased 4.8-fold at the end of 24 h. Presence of
      glucose and sucrose (1-10 mM), NaCl and KCI (5-100 mM), MgCl2 (1-10 mM) and BSA
      (10 to 500 microg per assay tube) do not interfere either with color development
      or with OD measurements. The extent of ATP hydrolysis is 1.6 to 3.4% for up to 1
      hi, depending upon the concentration of H2SO4 used. Only negligible hydrolysis of
      G6P is observed under these conditions. These results suggest that the presently
      modified method is suitable for Pi analysis in the enzyme assays, in the presence
      of labile phosphate containing substrates.

PMID- 17536337
TI  - Role of pepsin in modifying the allergenicity of bhetki (Lates calcarifer) and
      mackerel (Rastrelliger kanagurta) fish.
AB  - The effect of pepsin digestion on the allergenicity of raw and thermally
      processed (boiled and fried) fish muscle extracts of two widely consumed fishes
      bhetki (Lates calcarifer) and mackerel (Rastrelliger kanagurta) was studied. Sere
      were collected from 110 patients who were hypersensitive to fish, as evidenced by
      their clinical history, symptoms and positive skin-prick test results. The
      various extracts after digestion with pepsin at different times of incubation
      were tested for specific IgE-binding activity by ELISA and immunoblotting with
      patients' sera. All the extracts of both the fishes retained their allergenicity
      as evidenced by ELISA and immunoblotting. In bhetki, maximum allergenicity was
      found in the pepsin-digested fried extract, whereas similar treatment decreased
      the allergenicity in fried mackerel. Results showed that raw as well as thermally
      processed allergens of both the fishes maintained strong allergenicity, even
      after digestion with pepsin for different time periods. The study revealed that
      the fish proteins played an important role in manifestation of allergy, due to
      their stable structure, which was retained even after pepsin and heat treatment.

PMID- 17536338
TI  - Studies on interactions between plant secondary metabolites and glutathione
      transferase using fluorescence quenching method.
AB  - The interactions between plant secondary metabolites (tannic acid, rutin,
      cinnamic acid and catechin) and glutathione transferase (GST) were investigated
      by fluorescence and UV-Vis absorption spectroscopy. Intrinsic fluorescence of GST
      was measured by selectively exciting their tryptophan (Trp) residues and
      quenching constants were determined using the Stern-Volmer equation. The binding
      affinity was found to be strongest for tannic acid and ranked in the order tannic
      acid>rutin>cinnamic acid>catechin. The pH values in the range of 6.7-7.9, except
      for tannic acid, did not affect significantly the affinity of rutin, cinnamic
      acid and catechin with GST. Results showed that the fluorescence quenching of GST
      was a static_quenching. Fluorescence quenching and UV-Vis absorption spectroscopy
      suggested that only the tannic acid changed the microenvironment of the Trp
      residues. Furthermore, the number of binding sites and binding constants at
      different pH values showed that tannic acid had strongest affinity towards GST
      and hydrogen bonding played an important role in the affinity between GST and the
      metabolites.

PMID- 17536339
TI  - Construction and design of single stranded collagen-like structure.
AB  - Polytheonamide B, a 48 residue long highly cytotoxic polypeptide extracted from
      marine sponges contains amino acids of alternate chirality and the N-terminal
      region is rich in t-Leu residues. The aim of this study is to analyze the effect
      of these alternate chiralities and conformational behavior of various model
      peptides containing t-Leu, in order to explore their role in designing bioactive
      peptides that shall offer advantages comparable to polytheonamide B, while
      circumventing its limitations. The conformational behavior of various peptides
      constructed from t-Leu of the form Ac-(L/D-X-L/D-Y)n-NHMe, where X = Gly/Ala/Leu
      and Y = t-Leu has been studied and compared with the corresponding peptides
      containing Leu residue. The results show that the helix driving capacity of L and
      D forms of t-Leu is less than that of Leu residue. In poly t-Leu peptides, the
      population of collagen/inverse collagen-type structures or right/left handed
      helical structures for L and D forms respectively is found to be chain length
      dependent. The stability of the helical structures is increased by -2 kcal per
      residue over the collagen-type structure in poly t-Leu peptides with chain length
      greater than five residues. Molecular view of peptides in collagen-type structure
      shows that the bulky side chains of t-Leu residues mask the NH moieties of the
      peptide bond, while the carbonyl groups lying along the helical groove are
      accessible to the small solvent molecules. Molecular model building suggests that
      one ethylene glycol molecule interacts by forming hydrogen bonds with carbonyl
      groups of two adjacent t-Leu residues. To the best of our knowledge, this is the
      first study of its own kind on the construction of a single-strand
      collagen/inverse collagen-type structure using unusual amino acid residues. Such
      synthetic collagen mimetic peptides shall exhibit specific affinity to natural
      collagen under controlled thermal conditions (heat or laser treatment) and hence
      can be explored as a new targeting method to attach therapeutic drugs to
      collagens in the living tissues and to biomaterials that incorporate natural
      collagens.

PMID- 17536340
TI  - Exploring QSAR of peripheral benzodiazepine receptor binding affinity of N,N
      dialkyl-2-phenylindol-3-yl-glyoxylamides using physico-chemical descriptors.
AB  - The present QSAR study has attempted to explore the structural and
      physicochemical requirements of ligands N,N-dialkyl-2-phenylindol-3-yl
      glyoxylamides for binding with peripheral benzodiazepine receptor (PBR). The
      calculated partition coefficient values show parabolic relations with the PBR
      binding affinity, suggesting that the binding affinity increases with increase in
      the partition coefficient of the compounds until it reaches the critical value
      after which the affinity decreases. The critical value of logP is within range of
      6.052-6.410. Furthermore, positive Wang-Ford.charge values of carbonyl oxygens of
      the glyoxamide moiety and negative Wang-Ford charge value of the glyoxamide
      nitrogen are conducive for the binding affinity. Again, the indole moiety should
      have favorable charge distribution. Higher values of the parameters dipole moment
      (Dipole) and moment of inertia (I_z) of the ligands are conducive for the binding
      affinity. The presence of hydrogen atom at R2 and cyclic moiety at R1 and R2
      positions are detrimental to the binding affinity.

PMID- 17536341
TI  - Purification of protein from a crude mixture through SDS-PAGE transfer method.
AB  - SDS-polyacrylamide gel electrophoresis (SDS-PAGE) transfer method was used for
      purification and enrichment of the protein from crude sample. Coomassie
      bluc/ZnSO4 stained protein band(s) containing intact polyacrylamide gel were
      loaded on to another polyacrylamide gel either alone or as pooled gel bands.
      Two/three bands were combined together and arranged tightly over one another,
      sealed with stacking gel and ran in another gel, which was quite useful for
      enrichment and purification of a particular protein from a complex mixture.
      Recovery of protein by gel transfer method was found to be 70% in case of ZnSO4
      staining, whereas around 30% recovery was possible, following Coomassie blue
      staining. The method described here for purification of protein(s) from a complex
      mixture, following gel transfer procedure could be useful for further
      characterization of the desired protein.

PMID- 17536342
TI  - Optimizing palliative treatment of metastatic colorectal cancer in the era of
      biologic therapy.
AB  - Over the past decade, new cytotoxic and biologic therapies beyond the old
      standard-of-care, biomodulated fluorouracil (5-FU), have become available for the
      treatment of metastatic colorectal cancer (mCRC). The introductions of irinotecan
      (Camptosar), oxaliplatin (Eloxatin), and bevacizumab (Avastin) have prolonged
      survival, but the optimal use of these new therapies remains to be determined.
      Issues remain regarding management of toxicities, treatment of elderly patients
      or those with poor performance status, and the duration of treatment with front
      line therapy. This article reviews recent and ongoing studies of newer therapies
      in an effort to determine the best use of these drugs in the treatment of mCRC.
      Current data support the front-line use of bevacizumab added to either 5
      FU/leucovorin alone or 5-FU/leucovorin in combination with oxaliplatin
      (FOLFOX/bevacizumab) or irinotecan (FOLFIRI/bevacizumab). If oxaliplatin is used
      in first-line therapy, oxaliplatin should be discontinued before the development
      of severe neurotoxicity and be reintroduced or replaced with irinotecan on
      disease progression. Definitive conclusions on the sequence and duration of front
      line therapy and the most effective strategy to ameliorate toxicity await results
      of ongoing prospective clinical trials.

PMID- 17536343
TI  - Role of chemotherapy in the treatment of gastroesophageal cancers.
AB  - Esophageal, gastroesophageal junction, and gastric cancers are underpublicized
      but are frequently lethal, and gastroesophageal junction adenocarcinomas are
      increasingly common diseases in the United States and around the world. Although
      often grouped together in studies of chemotherapy, clear distinctions can be made
      in the locoregional therapy of these diseases. Esophageal squamous cell
      carcinomas may be treated with surgery or radiation with concurrent chemotherapy,
      whereas esophageal adenocarcinomas and gastroesophageal junction adenocarcinomas
      are often treated with all three treatment modalities. Over the past several
      years, it has become increasingly evident that gastric cancer is a disease that
      is potentially sensitive to chemotherapy. In the perioperative setting--at least
      in the Western world-chemotherapy and sometimes radiation are applied. However,
      the optimal chemotherapy for advanced gastric or esophageal cancer remains
      unsettled, and there is no single standard regimen. Several new chemotherapy
      agents have demonstrated activity in these diseases, but the best chemotherapy
      remains to be determined. This paper will review the role of chemotherapy in
      gastroesophageal cancers.

PMID- 17536344
TI  - Reproductive issues in the gynecologic cancer patient.
AB  - Clinicians, researchers, and survivorship communities are beginning to recognize
      the late effects of cancer treatment, such as infertility, and the negative
      impact this can have on cancer survivorship. Reproductive concerns that emerge
      within cancer experiences have been shown to be negatively associated with
      quality of life. Gynecologic cancer can present before childbearing has been
      started or completed, during pregnancy, or can even arise out of pregnancy, as is
      the case with gestational trophoblastic disease. Parenthood has been cited as an
      important aspect of cancer survivorship. As a result, interest concerning
      fertility preservation, reproductive concerns, and family-building options in
      cancer survivorship has increased, in addition to awareness of the emotional
      ramifications of cancer-related infertility. Education and support are clearly an
      essential component of cancer survivorship. Furthermore, more attention and
      investigation is still needed about the reproductive issues of gynecologic cancer
      survivors in the future.

PMID- 17536346
TI  - Crossing the quality chasm.

PMID- 17536345
TI  - Prostate cancer in a man with multiple previous cancers.

PMID- 17536347
TI  - [20 millions to primary health care for work with "risky use"].

PMID- 17536348
TI  - [How to avoid tattooes].

PMID- 17536349
TI  - [Prenatal ultrasonography requires medical indication. The risks are mostly
      uninvestigated, some findings are unsettling].

PMID- 17536350
TI  - [Brain concussion and sports--new guidelines for management].

PMID- 17536351
TI  - [Hospital infection--still surgeon's worst enemy. Simple measures with amazingly
      good results, shown in a project from 1970's].

PMID- 17536352
TI  - [The Medical Products Agency suggests improved drug safety follow-ups. New grasps
      of better knowledge and adverse effects reporting].

PMID- 17536353
TI  - [Education of mentors deepens education in communication skills. Better effect if
      the teachers have had the same education as the students].

PMID- 17536354
TI  - [Difficult ethics of prevention a challenge to the medical profession. Chasing
      risk factors can result in "health dictatorship"].

PMID- 17536355
TI  - [A letter from a physician to be. The first commandment of modern medicine--not
      to harm?].

PMID- 17536356
TI  - [Big changes in primary health in Stockholm. What will the customer choice model
      look like?].

PMID- 17536357
TI  - [Clustering of apathetic children will remain a difficult-to-explain phenomenon].

PMID- 17536358
TI  - [Stent treatment of carotid stenosis does have a future!].

PMID- 17536359
TI  - [Depo-Medrol--an alternative in the treatment of asthma].

PMID- 17536360
TI  - [The patient's drawings a key to disease from within].

PMID- 17536361
TI  - An aggregation pheromone modulates lekking behavior in the vector mosquito Aedes
      aegypti (Diptera: Culicidae).
AB  - Males of Aedes aegypti mosquitoes formed swarms in the laboratory, triggered by
      the onset of the photophase or by the presence of odors from a rat (which is a
      potential host for females). The swarm attracted both males and females and
      increased mating activity. The number of copulas per mosquito was positively
      correlated with the number of mosquitoes in the swarm and with the duration of
      the swarm. Swarming and mating activity increased with the presence of a host for
      females. Young sexually immature males, less than 24 h old, flew but did not
      swarm nor copulate. Observations using an olfactometer showed that swarming males
      produced a volatile pheromone that stimulates the flying activity of females at a
      distance. Females also produce a volatile attractant. The results suggest that
      males, and possibly also females, produce an aggregation pheromone that attracts
      males and females towards the swarm. The characteristics of the pheromone
      mediated swarm may be described as a 3-dimensional lek. Our results suggest that
      the development of pheromone-based control systems and/or pheromone traps for the
      monitoring of vector populations is feasible, adding a new tool to combat this
      vector of several human pathogens.

PMID- 17536362
TI  - Evaluation of carbon dioxide, 1-octen-3-ol, and lactic acid as baits in Mosquito
      Magnet Pro traps for Aedes albopictus in north central Florida.
AB  - The impact of the attractants l-octen-3-ol (octenol) and L-lactic acid (LurexTM)
      on collection of Aedes albopictus in suburban backyards was assessed in Mosquito
      Magnet Pro traps. These carbon dioxide-producing traps were additionally baited
      with commercial formulated lures with octenol, lactic acid, octenol + lactic
      acid, or no attractant (control) and evaluated in 4 residential sites. Three
      repetitions of the study resulted in the total collection of 1,321 Ae.
      albopictus. Significantly more Ae. albopictus were captured in traps baited with
      octenol + lactic acid than in traps baited only with octenol. Lactic acid-baited
      and control trap captures were not significantly different from octenol + lactic
      acid- or octenol-baited trap totals. Octenol- + lactic acid-baited traps
      collected 36.2% and 52.0% more Ae. albopictus than lactic acid-baited and control
      traps, respectively. Male Ae. albopictus accounted for 26.7% of the total
      capture. Other mosquito species collected in sufficient numbers for analysis
      included Cx. nigripalpus, Ochlerotatus infirmatus, Psorophoraferox, and Cx.
      erraticus. Larger numbers of these species were collected in traps that were
      unbaited or baited with only octenol than in traps baited with lactic acid or
      octenol + lactic acid.

PMID- 17536363
TI  - Attraction of gravid anopheles Pseudopunctipennis females to oviposition
      substrates by Spirogyra majuscula (Zygnematales: Zygnmataceae) algae under
      laboratory conditions.
AB  - The attraction of Anopheles pseudopunctipennis gravid females to oviposition
      substrates containing Spirogyra majuscula algae was investigated under laboratory
      conditions. Gravid females deposited significantly more eggs in cups containing
      natural algae in water from breeding sites than in cups containing artificial
      (nylon rope) life-like algae in water from the corresponding natural breeding
      site, or in cups containing natural algae in distilled water. Bioassays with
      Spirogyra majuscula organic extracts indicated that these extracts at
      concentrations of 0.1%, 0.01%, and 0.001% attracted more oviposition, but
      concentrations of 1%, 10%, and 100% were repellent. Gas chromatography and mass
      spectrometry analysis of algae organic extracts revealed a mixture of ethyl
      acetate and hydrocarbons compounds. These results suggest that the attraction of
      gravid An. pseudopunctipennis to natural breeding sites containing filamentous
      algae is probably mediated by organic compounds released by the algae.

PMID- 17536364
TI  - Synergism between cis-permethrin and benzoyl phenyl urea insect growth regulators
      against Aedes aegypti larvae.
AB  - Emulsifiable concentrate formulations of 2 insect growth regulator (IGR) benzoyl
      ureas (novaluron and diflubenzuron) and the pyrethroid cis-permethrin were
      individually bioassayed against late 3rd- or early 4th-stage larvae of
      susceptible Aedes aegypti. The emergence inhibition 50% were 0.038, 0.048, and
      0.179 ppb for novaluron, diflubenzuron, and cis-permethrin, respectively. We also
      tested 1:1 (v:v) mixtures of cis-permethrin and benzoyl ureas. Emergence
      inhibition 50% for novaluron plus cis-permethrin and diflubenzuron plus cis
      permethrin were 0.030 and 0.037, respectively, with combination indexes of 0.49
      and 0.56, indicating a synergistic interaction between these insecticides. The
      percentage of larval mortality produced by 0.5 ppb of the mixtures of cis
      permethrin and each IGR was compared to the addition of larval mortality produced
      in separated experiments by 0.25 ppb of each component, after 5, 9 and 13 days of
      continuous exposure. In all bioassays, the novaluron plus cis-permethrin mixture
      produced a significantly higher larvicidal effect (P < 0.05) compared with the
      individual contribution of each compound. The diflubenzuron plus cis-permethrin
      mixture showed significantly higher larval mortality (P < 0.05) compared with the
      contributive effect of each insecticide after 9 and 13 days of exposure, but
      there was no significant difference after 5 days of exposure.

PMID- 17536365
TI  - West Nile virus surveillance in East Baton Rouge Parish, Louisiana.
AB  - West Nile virus (WNV) was detected for the first time in Louisiana in the fall of
      2001. Surveillance data collected from East Baton Rouge Parish in 2002 were
      examined to establish baseline data on WNV activity, to support the current
      design of disease surveillance programs, and to target vector control efforts in
      the parish. The first indications of WNV activity were from a dead Northern
      Cardinal collected in February and from a live male cardinal sampled on 14 March.
      In mosquito pools, WNV was first detected on June 11. The onset of the first
      human case and the first detection of WNV in sentinel chickens occurred
      concurrently on June 24. The number of reported human cases and minimum infection
      rates in mosquitoes peaked in July. WNV prevalence in wild birds increased in
      late August and was highest in December. WNV-positive wild birds and mosquito
      pools were detected an average of 31 and 59 days in advance of the onset date of
      reported human cases, respectively, within 5 km of the residence of a human case.
      Antibodies to WNV were detected in sera from 7 (Northern Cardinal, House Sparrow,
      Northern Mockingbird, Blue Jay, Hermit Thrush, Yellow-rumped Warbler, and White
      throated Sparrow) of the 42 wild bird species tested. Wild bird serology
      indicated WNV activity during the winter. Out of 18 mosquito species tested, the
      only species found positive for WNV was Culex quinquefasciatus, a result
      suggesting that this species was the primary epizootic/epidemic vector.

PMID- 17536366
TI  - Entomological studies along the Colorado Front Range during a period of intense
      West Nile virus activity.
AB  - To better understand the ecology of West Nile virus transmission in Northern
      Colorado, field studies were conducted in Larimer and Weld counties from
      September 2003 through March 2005. During summer studies, 18,540 adult mosquitoes
      were collected using light traps and gravid traps. West Nile virus RNA was
      detected in 24 of the 2,140 mosquito pools tested throughout the study area in
      2003 and 2004. Culex tarsalis had the highest minimum infection rate (MIR) in
      both 2003 (MIR = 34.48) and in 2004 (MIR = 8.74). During winter studies, 9,391
      adult mosquitoes were collected by aspirator from various overwintering sites
      including bridges and storm drains. The most frequently collected species was
      Culex pipiens. West Nile virus was not detected in our overwintering collections.
      The relationship between spring adult emergence and temperature inside and
      outside overwintering sites is described. Species composition of collections as
      well as the spatial and temporal distribution of West Nile virus detections are
      presented.

PMID- 17536367
TI  - U.S. laboratory and field trials of metofluthrin (SumiOne) emanators for reducing
      mosquito biting outdoors.
AB  - Metofluthrin (SumiOne is a novel, vapor-active pyrethroid that is highly
      effective against mosquitoes. Laboratory and field trials were conducted in the
      United States to evaluate the mosquito repellent activity of metofluthrin-treated
      paper substrates ("emanators"). Initial studies were conducted to evaluate the
      field performance of 900-cm(2) paper fan emanators impregnated with 160 mg
      metofluthrin, where Aedes canadensis was the predominant species. Emanators
      reduced landing rates on human volunteers by between 85% and 100% compared to
      untreated controls. Subsequent tests with 4,000-cm(2) paper strip emanators
      impregnated with 200 mg metofluthrin were conducted in a wind tunnel as a
      precursor to conducting field trials using human bait and laboratory-reared Aedes
      aegypti. Paper strips, which were pre-aged in a fume hood to determine duration
      of protection, gave 89-91% reductions in landing rates compared with controls.
      Similar reductions in biting activity were also noted. Following these tests,
      field trials to assess effect on landing rates were conducted with emanators
      positioned 1.22 m on either side of volunteers protected from biting by Tyvek
      suits, with pre- and posttreatment counts being made. In Florida (predominantly
      Ochlerotatus spp.) 91-95% reductions were noted 10-30 min after emanators were
      deployed, while in Washington State (mostly Aedes vexans) 95-97% reductions were
      observed. These results demonstrate that metofluthrin-treated emanators are
      highly effective at repelling mosquitoes.

PMID- 17536368
TI  - Field tests of malathion and permethrin applied via a truck-mounted cold fogger
      to both open and vegetated habitats.
AB  - Field tests of formulated permethrin (Permanone 30:30) and malathion applied by
      ground ultra-low volume equipment were conducted using caged, laboratory-reared,
      adult Ochlerotatus taeniorhynchus. Cages were placed in an open field and also in
      semi-dense scrub pine. Two doses, a high and a medium dose of each compound, were
      applied as suggested by the label. Regardless of application rate, neither
      chemical provided satisfactory control under the canopy. The average mortality
      count at the open site and vegetated site was 86.6% and 49.1%, respectively
      (F.pr. < 0.001, SED 3.87). Malathion for both open and canopied areas achieved
      significantly greater mortality compared to permethrin.

PMID- 17536369
TI  - A novel method for evaluating the particle distributional behavior of a spray
      dried technical concentrate and a water-dispersible granule formulation of
      Bacillus thuringiensis subsp. Israelensis in an aqueous column.
AB  - A novel method for evaluating the particle behavior of a spray-dried technical
      concentrate and a water-dispersible granule (WDG) formulation of B. thuringiensis
      subsp. israelensis in an aqueous column was established. The objective was to
      determine the distributional behavior (minus any extraneous environmental
      factors) of B. thuringiensis subsp. israelensis within a water column over time.
      Studies showed a fairly even distribution of particles over a 16-h period for the
      technical concentrate and WDG formulation. The particle behavior of the WDG
      formulation also showed homogeneous distribution of particles at 64 and 128 h.
      The results demonstrated that Brownian motion plays a significant role in the
      particle distributional behavior of this entomopathogen.

PMID- 17536370
TI  - Effects of vegetation control on mosquitoes in seasonal freshwater wetlands.
AB  - Wetland restorations benefit wildlife, but wetland vegetation may promote
      mosquitoes. We studied the effects of removing joint grass (Paspalum distichum
      L.) on the abundance and distribution of immature mosquitoes in seasonal
      freshwater wetlands in California. In 4 >4-ha plots and one 29.8-ha field, joint
      grass was removed via herbicide and disking. Four untreated plots and one 4.1-ha
      field were controls. Fields were sampled every 7-14 days in early autumn by
      taking 75 dips along levees, plus a 25-dip circular transect 6 m from field
      edges. Untreated plots had 7 times more larvae and 20 times more pupae than did
      vegetation-removal plots. Similar densities of mosquitoes were found along edges
      and within fields.

PMID- 17536371
TI  - Recognition of a novel melanotic mutant in a field population of Culex pipiens
      quinquefasciatus in southern Zambia.
AB  - Genetic mutations controlling eye color, fat body color, structural
      abnormalities, and insecticide resistance are common in mosquitoes. We have
      identified a novel color variant of Culex pipiens quinquefasciatus characterized
      by a heavily pigmented integument in adult specimens circulating in field
      populations of this species in southern Zambia. Mosquitoes were collected monthly
      by pyrethrum spray catch between November and May 2004-05 and 2005-06, with
      between 25% and 80% of the total Cx. p. quinquefasciatus collections comprising
      this pigmented variety. The identity of pigmented specimens was morphologically
      confirmed as Cx. p. quinquefasciatus by examination of orientation of the dorsal
      and ventral arms of the male genitalia of F1 male progeny reared in the
      laboratory, and molecularly verified by diagnostic polymerase chain reaction and
      nicotinamide adenine dinucleotide phosphate dehydrogenase subunit 4 nucleotide
      sequence homology. Preliminary laboratory rearings indicated that the
      pigmentation was heritable and not influenced by larval habitat and environmental
      conditions. Further investigation into the mechanism of the mutation, inheritance
      patterns, and potential linkage to additional markers is pending.

PMID- 17536372
TI  - Addition of three species of Topomyia (Diptera: Culicidae) to the mosquito fauna
      of Northeastern India.
AB  - Topomyia (Topomyia) hirtusa, Topomyia (Topomyia) bifurcata, and Topomyia
      (Suaymyia) cristata are recorded for the first time in India from the
      northeastern state of Arunachal Pradesh.

PMID- 17536373
TI  - First records for Culex (Melanoconion) limacifer Komp and Culex (Melanoconion)
      dunni dyar from Guatemala.
AB  - Larvae of Culex (Melanoconion) limacifer Komp and Culex (Melanoconion) dunni Dyar
      were collected during June 2004 in Guatemala. All specimens were individually
      reared to the adult stage. Specimens were identified based upon examination of
      the male genitalia and characters of the associated larval and pupal exuviae.
      These are the first records of these 2 species in Guatemala.

PMID- 17536374
TI  - Male genitalia of flesh fly Parasarcophaga (Liosarcophaga) dux (Diptera:
      Sarcophagidae) revealed by scanning electron microscopy.
AB  - The male genitalia of flesh fly Parasarcophaga (Liosarcophaga) dux (Diptera:
      Sarcophagidae) was observed using scanning electron microscopy (SEM). The phallus
      is a short, broad structure that is formed by a tubular base connected to a
      trumpet-shaped, anteroventrally expanded ventralia. The juxta projects forward
      from a broad base, which is connected to an upright long structure, the harpes.
      The juxta is apically bifurcated. The lateral styli bear three small spines
      curved inward. The pregonite and postgonite are slightly curved upward apically.
      The cerci are pointed and curved apically. Sensillae were observed on the
      surfaces of postgonite, surstylus, epandrium, and cerci.

PMID- 17536375
TI  - Description of three practical and inexpensive devices for the collection of
      mosquitoes and other small insects.
AB  - Three new devices for collecting and maintaining mosquitoes and other small
      insects are described. A suction tube, composed of two pieces of plastic
      transparent tube, the narrower fitted in the wider, with the mouth protected by
      the use of voile, is cheap and practical and can be transported around the neck.
      A 900-ml plastic transparent box is utilized for the restraint of sucked insects
      and, with the adaptation of two pieces of plastic tube, as a suction chamber.

PMID- 17536376
TI  - Turn evaluations into mentoring sessions.

PMID- 17536377
TI  - Old dominion embraces transformation.

PMID- 17536378
TI  - Workplace drug testing's mixed success.

PMID- 17536379
TI  - The importance of compliance planning.

PMID- 17536380
TI  - Clients' role in fire prevention.

PMID- 17536381
TI  - Pay attention to details.

PMID- 17536382
TI  - EASNA update.

PMID- 17536383
TI  - Responding during tough economic times.

PMID- 17536384
TI  - Improving aftercare effectiveness.

PMID- 17536385
TI  - Anticipating the worst.

PMID- 17536386
TI  - Connecting the docs.

PMID- 17536387
TI  - The importance of early treatment of schizophrenia.
AB  - It is extremely important to treat schizophrenia as soon as possible after the
      onset. With delay in effective treatment, patients may be at increased risk for
      brain volume loss with adverse implications for long-term treatment outcomes.
      Providers should not try to "instruct" patients with schizophrenia, who often
      have impaired verbal learning abilities, about the necessity of adhering to their
      medication regimen, but instead should try to demonstrate that the treatment can
      effectively improve their lives. To this end, it is crucial to find a medication
      at a dose that relieves psychotic and affective psychopathology as quickly as
      possible. To optimize treatment adherence, it seems more practical for providers
      to help patients with schizophrenia feel subjectively better and recognize
      improvement than to impress them with the logic of the argument for taking
      medications. In treating schizophrenia, physicians also should be involved and
      accessible to patients and caregivers. Providers should treat their patients with
      respect, express their viewpoint succinctly and consistently, and make clear that
      the betterment of the patient is their goal.

PMID- 17536388
TI  - Returning vets need a network of care.

PMID- 17536389
TI  - Linking research and practice.

PMID- 17536390
TI  - Emphasizing the greater good.

PMID- 17536391
TI  - Stranger in a strange land.

PMID- 17536392
TI  - Negative selection effects suppress relationships between bacterial diversity and
      ecosystem functioning.
AB  - I assembled bacterial communities to explore the effects of bacterial diversity
      on multiple ecosystem functions, including bacterial community biovolume,
      decomposition of particulate organic matter, and biomass transfer to the next
      trophic level. The experiment used a two-way factorial design with four levels of
      bacterial diversity (one to four species) and the absence/presence of a
      bacterivorous ciliated protist Tetrahymena pyriformis as two main factors, and
      all possible combinations of the four bacterial taxa nested within each diversity
      level. Bacterial community biovolume increased as bacterial diversity increased,
      a result due largely to positive selection effects. Decomposition and consumer
      abundance, however, were unaffected by bacterial diversity, though both varied
      among bacterial composition treatments. Negative selection effects, the dominance
      of species that do not contribute significantly to ecosystem functioning,
      accounted for the lack of diversity effects on decomposition and consumer
      abundance. The presence of Tetrahymena reduced bacterial community biovolume but
      increased decomposition, without altering the diversity-functioning
      relationships. Decomposition was strongly linked with consumer abundance such
      that communities supporting larger consumer biomass exhibited higher
      decomposition rates. This study suggests that if the negative selection effect is
      common, as it might be when examining ecosystem variables other than biomass (due
      to the presence of keystone species that can contribute disproportionably to
      ecosystem functioning relative to their abundances), basic bacteria-mediated
      ecosystem processes, such as decomposition and energy transfer to the next
      trophic level, may not increase with bacterial diversity.

PMID- 17536393
TI  - Bet hedging in a guild of desert annuals.
AB  - Evolutionary bet hedging encapsulates the counterintuitive idea that organisms
      evolve traits that reduce short-term reproductive success in favor of longer-term
      risk reduction. It has been widely investigated theoretically, and many putative
      examples have been cited including practical ones such as the dormancy involved
      in microbe and weed persistence. However, long-term data on demographic variation
      from the actual evolutionarily relevant environments have been unavailable to
      test for its mechanistic relationship to alleged bet hedging traits. I report an
      association between delayed germination (a bet hedging trait) and risk using a 22
      year data set on demographic variation for 10 species of desert annual plants.
      Species with greater variation in reproductive success (per capita survival from
      germination to reproduction x per capita fecundity of survivors) were found to
      have lower average germination fractions. This provides a definitive test using
      realistic data on demographic variance that confirms the life history prediction
      for bet hedging. I also showed that the species with greater long-term
      demographic variation tended to be the ones with greater sensitivity of
      reproductive success to variation among years in growing-season precipitation.

PMID- 17536394
TI  - Contrasting plant productivity-diversity relationships across latitude: the role
      of evolutionary history.
AB  - The relationship between net primary productivity and biological diversity has
      been a central topic in ecology for several decades. The unimodal ("hump-back")
      relationship has been the most widely accepted for plants with the decrease in
      diversity at high productivity usually attributed to competitive exclusion.
      However, the relatively small species pool size under high productivity
      conditions may account for this pattern as well. Small species pool sizes for
      highly productive habitats are characteristic of temperate regions, where
      productive habitats for speciation and species migration have historically been
      rare. In contrast, productive habitats in the tropics have been relatively common
      during evolutionary history, resulting in large species pools. We hypothesize
      that evolutionary history contributes to the observed productivity-diversity
      relationship of plants, and that the productivity-diversity relationship differs
      between temperate and tropical regions. We investigated the productivity
      diversity relationship patterns from 163 case studies throughout the world.
      Latitude described approximately 80% of the variation in the shape of the
      relationships. The unimodal relationship was found to dominate in the temperate
      zone, whereas the positive relationship was significantly more common in the
      tropics. We detected no influence due to methods of productivity measurement, but
      unimodal or positive productivity-diversity relationships were more likely within
      larger ranges of productivity. The length of the productivity gradient did not
      affect the latitudinal influence. In summary, the shape of the productivity
      diversity relationship differs between temperate and tropical regions and the
      different evolutionary history of the local species pools is a probable cause for
      the difference.

PMID- 17536395
TI  - Native and exotic plant species exhibit similar population dynamics during
      succession.
AB  - A growing body of literature has led to the debate in invasion biology whether
      exotic species perform within communities differently than native taxa due to
      inherent advantages. To address this issue, the population dynamics of native and
      exotic plant species were assessed from a 48-year record of permanent plot data
      from the Hutcheson Memorial Forest Center (New Jersey, USA) to determine rate of
      increase, lag time, maximum frequency, and the year of peak frequency. Overall,
      native and exotic species exhibited very similar population dynamics. Rates of
      increase and length of lag times were similar between native and exotic taxa but
      were strongly influenced by plant life form. Short-lived species were
      characterized by rapid population growth rates and short lag times. Growth rates
      decreased and lag times increased with species longevity. Overall, correlations
      between population metrics were the same in native and exotic taxa, suggesting
      similar trade-offs in life history patterns. The one difference observed was
      that, in native species, peak frequency was negatively associated with the year
      of peak frequency (i.e., early-successional species tended to become more
      abundant), while there was no relationship in exotic species. These analyses show
      that exotic species behave in essentially the same way as native taxa within
      dynamic communities. This suggests that abundant native and exotic plant species
      are exploiting the same range of ecological strategies resulting in similar roles
      within communities.

PMID- 17536396
TI  - Herbivory limits recruitment in an old-field seed addition experiment.
AB  - Environmental variability can promote coexistence by creating establishment sites
      for rare plants, but low diversity in anthropogenic grasslands suggests that this
      variability may be eliminated (homogenization hypothesis) or inaccessible
      (barrier hypothesis). We explore these alternatives on the northern Great Plains,
      where 11 million hectares have been transformed by multiple environmental
      changes, but the causes of species loss are unclear. In a degraded grassland, we
      increased environmental variability by manipulating competition and herbivory
      along gradients of fertility and disturbance, and we circumvented dispersal
      barriers by adding 1.2 million seeds of five functionally distinct species at
      varying densities. The experiment ended after 12 weeks due to the direct and
      indirect effects of unapparent small native herbivores, which were barriers to
      population establishment by the added species. The direct cause of recruitment
      failure was browsing. The indirect cause was associated with competition from
      invasive plants that appeared to be more tolerant or resistant to herbivory.
      Variability in fertility, disturbance, propagule pressure, and competition had
      relatively minor impacts on colonization by the added species because herbivores
      controlled recruitment in most environments. Recruitment outside the herbivore
      exclosures was mostly by unpalatable exotics, suggesting a possible link between
      invasion success and herbivore resistance for some introduced plants.

PMID- 17536397
TI  - Spatial selection and inheritance: applying evolutionary concepts to population
      dynamics in heterogeneous space.
AB  - Organisms in highly suitable sites generally produce more offspring, and
      offspring can inherit this suitability by not dispersing far. This combination of
      spatial selection and spatial inheritance acts to bias the distribution of
      organisms toward suitable sites and thereby increase mean fitness (i.e., per
      capita population increase). Thus, population growth rates in heterogeneous space
      change over time by a process conceptually analogous to evolution by natural
      selection, opening avenues for theoretical cross-pollination between evolutionary
      biology and ecology. We operationally define spatial inheritance and spatial
      selective differential and then combine these two factors in a modification of
      the breeder's equation, derived from simple models of population growth in
      heterogeneous space. The modified breeder's equation yields a conservative
      criterion for persistence in hostile environments estimable from field
      measurements. We apply this framework for understanding gypsy moth population
      persistence amidst abundant predators and find that the predictions of the
      modified breeder's equation match initial changes in population growth rate in
      independent simulation output. The analogy between spatial dynamics and natural
      selection conceptually links ecology and evolution, provides a spatially implicit
      framework for modeling spatial population dynamics, and represents an important
      null model for studying habitat selection.

PMID- 17536398
TI  - Effects of four decades of fire manipulation on woody vegetation structure in
      Savanna.
AB  - The amount of carbon stored in savannas represents a significant uncertainty in
      global carbon budgets, primarily because fire causes actual biomass to differ
      from potential biomass. We analyzed the structural response of woody plants to
      long-term experimental burning in savannas. The experiment uses a randomized
      block design to examine fire exclusion and the season and frequency of burn in
      192 7-ha experimental plots located in four different savanna ecosystems.
      Although previous studies would lead us to expect tree density to respond to the
      fire regime, our results, obtained from four different savanna ecosystems,
      suggest that the density of woody individuals was unresponsive to fire. The
      relative dominance of small trees was, however, highly responsive to fire regime.
      The observed shift in the structure of tree populations has potentially large
      impacts on the carbon balance. However, the response of tree biomass to fire of
      the different savannas studied were different, making it difficult to generalize
      about the extent to which fire can be used to manipulate carbon sequestration in
      savannas. This study provides evidence that savannas are demographically
      resilient to fire, but structurally responsive.

PMID- 17536399
TI  - Extending the leaf economics spectrum to decomposition: evidence from a tropical
      forest.
AB  - I investigated the relationship between leaf physiological traits and
      decomposition of leaf litter for 35 plant species of contrasting growth forms
      from a lowland tropical forest in Panama to determine whether leaf traits could
      be used to predict decomposition. Decomposition rate (k) was correlated with
      specific leaf area (SLA), leaf nitrogen (N), phosphorus (P), and potassium (K)
      across all species. Photosynthetic rate per unit mass (Amass) was not correlated
      with k, but structural equation modeling showed support for a causal model with
      significant indirect effects of Amass on k through SLA, N, and P, but not K. The
      results indicate that the decomposability of leaf tissue in this tropical forest
      is related to a global spectrum of leaf economics that varies from thin, easily
      decomposable leaves with high nutrient concentrations and high photosynthetic
      rates to thick, relatively recalcitrant leaves with greater physical toughness
      and defenses and low photosynthetic rates. If this pattern is robust across
      biomes, then selection for suites of traits that maximize photosynthetic carbon
      gain over the lifetime of the leaf may be used to predict the effects of plant
      species on leaf litter decomposition, thus placing the ecosystem process of
      decomposition in an evolutionary context.

PMID- 17536400
TI  - Scaling mass and morphology in leaves: an extension of the WBE model.
AB  - Recent advances in metabolic scaling theory have highlighted the importance of
      exchange surfaces and vascular network geometry in understanding the integration
      and scaling of whole-plant form and function. Additional work on leaf form and
      function has also highlighted general scaling relationships for many leaf traits.
      However, it is unclear if a common theoretical framework can reveal the general
      rules underlying much of the variation observed in scaling relationships at the
      whole-plant and leaf level. Here we present an extension of the general model
      introduced by G. B. West, J. H. Brown, and B. J. Enquist that has previously been
      applied to scaling phenomena for whole plants to predict scaling relationships in
      leaves. Specifically, the model shows how the exponents that describe the scaling
      of leaf surface area, length, and petiole diameter should change with increasing
      leaf mass (or with one another) and with variation in leaf dimensionality. The
      predictions of the model are tested and found to be in general agreement with a
      large data set of leaves collected from both temperate and arid sites. Our
      results demonstrate that a general model based on the scaling properties of
      biological distribution networks can also be successfully applied to understand
      the diversity of leaf form and function.

PMID- 17536401
TI  - Grazers, producer stoichiometry, and the light : nutrient hypothesis revisited.
AB  - The stoichiometric light:nutrient hypothesis (LNH) links the relative supplies of
      key resources with the nutrient content of tissues of producers. This resource
      driven variation in producer stoichiometry, in turn, can mediate the efficiency
      of grazing. Typically, discussions of the LNH attribute this resource
      stoichiometry link to bottom-up effects of light and phosphorus, which are
      mediated through producer physiology. Emphasis on bottom-up effects implies that
      grazers must consume food of quality solely determined by resource supply to
      ecosystems (i.e., they eat what they are served). Here, we expand upon this
      largely bottom-up interpretation with evidence from pond surveys, a mesocosm
      experiment, and a model. Data from shallow ponds showed the "LNH pattern"
      (positive correlation of an index of light : phosphorus supply with algal carbon
      : phosphorus content). However, algal carbon : phosphorus content also declined
      as zooplankton biomass increased in the ponds. The experiment and model confirmed
      that this latter correlation was partially caused by the various bottom-up and
      top-down roles of grazers: the LNH pattern emerged only in treatments with
      crustacean grazers, not those without them. Furthermore, model and experiment
      clarified that another bottom-up factor, natural covariation of nitrogen :
      phosphorus ratios with light : phosphorus supply (as seen in ponds), does not
      likely contribute to the LNH pattern. Finally, the experiment produced
      correlations between shifts in species composition of algae, partially driven by
      grazing effects of crustaceans, and algal stoichiometry. These shifts in species
      composition might shape stoichiometric response of producer assemblages to
      resource supply and grazing, but their consequences remain largely unexplored.
      Thus, this study accentuated the importance of grazing for the LNH; de-emphasized
      a potentially confounding, bottom-up factor (covarying nitrogen : phosphorus
      supply); and highlighted an avenue for future research for the LNH (grazer
      mediated shifts in producer composition).

PMID- 17536402
TI  - Dynamics of nitrogen and dissolved organic carbon at the Hubbard brook
      experimental forest.
AB  - The factors controlling spatial and temporal patterns in soil solution and
      streamwater chemistry are highly uncertain in northern hardwood forest ecosystems
      in the northeastern United States, where concentrations of reactive nitrogen (Nr)
      in streams have surprisingly declined over recent decades in the face of
      persistent high rates of atmospheric Nr deposition and aging forests. Reactive
      nitrogen includes inorganic species (e.g., ammonium [NH4+], nitrate [NO3-]) and
      some organic forms (e.g., amino acids) available to support the growth of plants
      and microbes. The objective of this study was to examine controls on the spatial
      and temporal patterns in the concentrations and fluxes of nitrogen (N) species
      and dissolved organic carbon (DOC) in a 12-year record of soil solutions and
      streamwater along an elevational gradient (540-800 m) of a forested watershed at
      the Hubbard Brook Experimental Forest (HBEF) in the White Mountains of New
      Hampshire, USA. Dissolved organic N and DOC concentrations were elevated in the
      high-elevation spruce-fir-white birch (SFB) zone of the watershed, while NO3- was
      the dominant N species in the lower elevation hardwood portion of the watershed.
      Within the soil profile, N retention was centered in the mineral horizon, and
      significant amounts of N were retained between the lower mineral soil and the
      stream, supporting the idea that near- and in-stream processes are significant
      sinks for N at the HBEF. Temporal analysis suggested that hydrologic flow paths
      can override both abiotic and biotic retention mechanisms (i.e., during the non
      growing season when most hydrologic export occurs, or during years with high
      rainfall), there appears to be direct flushing of N from the organic horizons
      into the stream via horizontal flow. Significant correlations between soil NO3-
      concentrations, nitrification rates and streamwater NO3- exports show the
      importance of biological production as a regulator of inorganic N export. The
      lack of internal production response (e.g., mineralization, nitrification) to a
      severe ice storm in 1998 reinforces the idea that plant uptake is the dominant
      regulator of export response to disturbance.

PMID- 17536403
TI  - Nonadditive effects of leaf litter species diversity on breakdown dynamics in a
      detritus-based stream.
AB  - Since species loss is predicted to be nonrandom, it is important to understand
      the manner in which those species that we anticipate losing interact with other
      species to affect ecosystem function. We tested whether litter species diversity,
      measured as richness and composition, affects breakdown dynamics in a detritus
      based stream. Using full-factorial analyses of single- and mixed-species leaf
      packs (15 possible combinations of four dominant litter species; red maple [Acer
      rubrum], tulip poplar [Liriodendron tulipifera], chestnut oak [Quercus prinus],
      and rhododendron [Rhododendron maximum]), we tested for single-species
      presence/absence (additive) or species interaction (nonadditive) effects on leaf
      pack breakdown rates, changes in litter chemistry, and microbial and
      macroinvertebrate biomass. Overall, we found significant nonadditive effects of
      litter species diversity on leaf pack breakdown rates, which were explained both
      by richness and composition. Leaf packs containing higher litter species richness
      had faster breakdown rates, and antagonistic effects of litter species
      composition were observed when any two or three of the four litter species were
      mixed. Less-consistent results were obtained with respect to changes in litter
      chemistry and microbial and macroinvertebrate biomass. Our results suggest that
      loss of litter species diversity will decrease species interactions involved in
      regulating ecosystem function. To that end, loss of species such as eastern
      hemlock (Tsuga canadensis) accompanied by predicted changes in riparian tree
      species composition in the southeastern United States could have nonadditive
      effects on litter breakdown at the landscape scale.

PMID- 17536404
TI  - Twenty years of changes in spatial association and community structure among
      desert perennials.
AB  - I present results from analyses of 20 years of spatiotemporal dynamics in a
      desert perennial community. Plants were identified and mapped in a 1-ha permanent
      plot in Joshua Tree National Park (California, USA) in 1984. Plant size,
      mortality, and new seedlings were censused every five years through 2004. Two
      species, Ambrosia dumosa and Tetracoccus hallii, were dominant based on their
      relative abundance and ubiquitous distributions. Spatial analysis for distance
      indices (SADIE) identified regions of significantly high (patches) or low (gaps)
      densities. I used SADIE to test for (1) transience in the distribution of patches
      and gaps within species over time and (2) changes in juvenile-adult associations
      with conspecific adults and adults of the two dominant species over time. Plant
      performance was quantified in patches and gaps to determine plant responsiveness
      to local spatial associations. Species identity was found to influence
      associations between juveniles and adults. Juveniles of all species showed
      significant positive spatial associations with the dominant A. dumosa but not
      with T. hallii. The broad distribution of A. dumosa may increase the spatial
      extent of non-dominant species that are facilitated by this dominant. The spatial
      location of patches and gaps was generally consistent over time for adults but
      not juveniles. Observed variability in the locations of juvenile patches and gaps
      suggested that suitable locations for establishment were broad relative to
      occupied regions of the habitat, and that conditions for seed germination were
      independent of conditions for seedling survival. A dramatic change in spatial
      distributions and associations within and between species occurred after a major
      drought that influenced data from the final census. Positive associations between
      juveniles and adults of all species were found independent of previous
      associations and most species distributions contracted to areas that were
      previously characterized by low density. By linking performance to spatial
      distribution, results from this study offer a spatial context for plant-plant
      interactions within and among species. Community composition could be influenced
      both by individual species tolerances of abiotic conditions and by the
      competitive or facilitative interactions individuals exert over neighbors.

PMID- 17536405
TI  - Rainfall and soils modify plant community response to grazing in Serengeti
      National Park.
AB  - Terrestrial plant community responses to herbivory depend on resource
      availability, but the separate influences of different resources are difficult to
      study because they often correlate across natural environmental gradients. We
      studied the effects of excluding ungulate herbivores on plant species richness
      and composition, as well as available soil nitrogen (N) and phosphorus (P),
      across eight grassland sites in Serengeti National Park (SNP), Tanzania. These
      sites varied independently in rainfall and available soil N and P. Excluding
      herbivores decreased plant species richness at all sites and by an average of 5.4
      species across all plots. Although plant species richness was a unimodal function
      of rainfall in both grazed and ungrazed plots, fences caused a greater decrease
      in plant species richness at sites of intermediate rainfall compared to sites of
      high or low rainfall. In terms of the relative or proportional decreases in plant
      species richness, excluding herbivores caused the strongest relative decreases at
      lower rainfall and where exclusion of herbivores increased available soil P.
      Herbivore exclusion increased among-plot heterogeneity in species composition but
      decreased coexistence of congeneric grasses. Compositional similarity between
      grazed and ungrazed treatments decreased with increasing rainfall due to greater
      forb richness in exclosures and greater sedge richness outside exclosures and was
      not related to effects of excluding herbivores on soil nutrients. Our results
      show that plant resources, especially water and P, appear to modulate the effects
      of herbivores on tropical grassland plant diversity and composition. We show that
      herbivore effects on soil P may be an important and previously unappreciated
      mechanism by which herbivores influence plant diversity, at least in tropical
      grasslands.

PMID- 17536406
TI  - Density-dependent effects of ants on selection for bumble bee pollination in
      Polemonium viscosum.
AB  - Mutualisms are commonly exploited by cheater species that usurp rewards without
      providing reciprocal benefits. Yet most studies of selection between mutualist
      partners ignore interactions with third species and consequently overlook the
      impact of cheaters on evolution in the mutualism. Here, we explicitly investigate
      how the abundance of nectar-thieving ants (cheaters) influences selection in a
      pollination mutualism between bumble bees and the alpine skypilot, Polemonium
      viscosum. As suggested in past work with this species, bumble bees accounted for
      most of the seed production (78% +/- 6% [mean +/- SE]) in our high tundra study
      population and, in the absence of ants, exerted strong selection for large
      flowers. We tested for indirect effects of ant abundance on seed set through
      bumble bee pollination services (pollen delivery and pollen export) and a direct
      effect through flower damage. Ants reduced seed set per flower by 20% via flower
      damage. As ant density increased within experimental patches, the rate of flower
      damage rose, but pollen delivery and export did not vary significantly, showing
      that indirect effects of increased cheater abundance on pollinator service are
      negligible in this system. To address how ants affect selection for plant
      participation in the pollination mutualism we tested the impact of ant abundance
      on selection for bumble bee-mediated pollination. Results show that the impact of
      ants on fitness (seed set) accruing under bumble bee pollination is density
      dependent in P. viscosum. Selection for bumble bee pollination declined with
      increasing ant abundance in experimental patches, as predicted if cheaters
      constrain fitness returns of mutualist partner services. We also examined how ant
      abundance influences selection on flower size, a key component of plant
      investment in bumble bee pollination. We predicted that direct effects of ants
      would constrain bumble bee selection for large flowers. However, selection on
      flower size was significantly positive over a wide range of ant abundance (20-80%
      of plants visited by ants daily). Although high cheater abundance reduces the
      fitness returns of bumble bee pollination, it does not completely eliminate
      selection for bumble bee attraction in P. viscosum.

PMID- 17536407
TI  - When there is no escape: the effects of natural enemies on native, invasive, and
      noninvasive plants.
AB  - An important question in the study of biological invasions is the degree to which
      successful invasion can be explained by release from control by natural enemies.
      Natural enemies dominate explanations of two alternate phenomena: that most
      introduced plants fail to establish viable populations (biotic resistance
      hypothesis) and that some introduced plants become noxious invaders (natural
      enemies hypothesis). We used a suite of 18 phylogenetically related native and
      nonnative clovers (Trifolium and Medicago) and the foliar pathogens and
      invertebrate herbivores that attack them to answer two questions. Do native
      species suffer greater attack by natural enemies relative to introduced species
      at the same site? Are some introduced species excluded from native plant
      communities because they are susceptible to local natural enemies? We address
      these questions using three lines of evidence: (1) the frequency of attack and
      composition of fungal pathogens and herbivores for each clover species in four
      years of common garden experiments, as well as susceptibility to inoculation with
      a common pathogen; (2) the degree of leaf damage suffered by each species in
      common garden experiments; and (3) fitness effects estimated using correlative
      approaches and pathogen removal experiments. Introduced species showed no
      evidence of escape from pathogens, being equivalent to native species as a group
      in terms of infection levels, susceptibility, disease prevalence, disease
      severity (with more severe damage on introduced species in one year), the
      influence of disease on mortality, and the effect of fungicide treatment on
      mortality and biomass. In contrast, invertebrate herbivores caused more damage on
      native species in two years, although the influence of herbivore attack on
      mortality did not differ between native and introduced species. Within introduced
      species, the predictions of the biotic resistance hypothesis were not supported:
      the most invasive species showed greater infection, greater prevalence and
      severity of disease, greater prevalence of herbivory, and greater effects of
      fungicide on biomass and were indistinguishable from noninvasive introduced
      species in all other respects. Therefore, although herbivores preferred native
      over introduced species, escape from pest pressure cannot be used to explain why
      some introduced clovers are common invaders in coastal prairie while others are
      not.

PMID- 17536408
TI  - Intraspecific competition: the role of lags between attack and death in host
      parasitoid interactions.
AB  - Many natural enemies do not immediately kill their host, and the lag this creates
      between attack and host death results in mixed populations of uninfected and
      infected hosts. Both competition and parasitism are known to be major structuring
      forces in ecological communities; however, surprisingly little is known about how
      the competitive nature of infected hosts could affect the survival and dynamics
      of remaining uninfected host populations. Using a laboratory system comprising
      the Indian meal moth, Plodia interpunctella, and a solitary koinobiont
      parasitoid, Venturia canescens, we address this question by conducting replicated
      competition experiments between the unparasitized and parasitized classes of host
      larvae. For varying proportions of parasitized host larvae and competitor
      densities, we consider the effects of competition within (intraclass) and between
      (interclass) unparasitized and parasitized larvae on the survival, development
      time, and size of adult moths and parasitoid wasps. The greatest effects were on
      survival: increased competitor densities reduced survival of both parasitized and
      unparasitized larvae. However, unparasitized larvae survival, but not parasitized
      larvae survival, was reduced by increasing interclass competition. To our
      knowledge, this is the first experimental demonstration of the competitive
      superiority of parasitized over unparasitized hosts for limiting resources. We
      discuss possible mechanisms for this phenomenon, why it may have evolved, and its
      possible influence on the stability of host-parasite dynamics.

PMID- 17536409
TI  - Asymmetric competition via induced resistance: specialist herbivores indirectly
      suppress generalist preference and populations.
AB  - Species may compete indirectly by altering the traits of a shared resource. For
      example, herbivore-induced responses in plants may make plants more resistant or
      susceptible to additional herbivorous insect species. Herbivore-induced plant
      responses can significantly affect interspecific competition and herbivore
      population dynamics. These herbivore-herbivore indirect interactions have been
      overlooked in aquatic ecosystems where previous studies used the same herbivore
      species to induce changes and to assess the effects of these changes. We asked
      whether seaweed grazing by one of two herbivorous, congeneric snail species
      (Littorina obtusata or Littorina littorea) with different feeding strategies and
      preferences would affect subsequent feeding preferences of three herbivore
      species (both snails and the isopod Idotea baltica) and population densities of
      three herbivore species (both snails and a third periwinkle snail, Lacuna
      vincta). In addition, we measured phlorotannin concentrations to test the
      hypothesis that these metabolites function as induced defenses in the
      Phaeophyceae. Snail herbivory induced cue-specific responses in apical tissues of
      the seaweed Fucus vesiculosus that affected the three herbivore species
      similarly. When compared to ungrazed controls, direct grazing by Littorina
      obtusata reduced seaweed palatability by at least 52% for both snail species and
      the isopod species. In contrast, direct grazing by L. littorea did not decrease
      seaweed palatability for any herbivore, indicating herbivore-specific responses.
      Previous grazing by L. obtusata reduced populations of L. littorea on outplanted
      seaweeds by 46% but had no effect on L. obtusata populations. Phlorotannins, a
      potential class of inducible chemicals in brown algae, were not more concentrated
      in grazed seaweed tissues, suggesting that some other trait was responsible for
      the induced resistance. Our results indicate that marine herbivores may compete
      via inducible responses in shared seaweeds. These plant-mediated interactions
      were asymmetric with a specialist (L. obtusata) competitively superior to a
      generalist (L. littorea).

PMID- 17536410
TI  - The scale and cause of spatial heterogeneity in strength of temporal density
      dependence.
AB  - The importance of density dependence in natural communities continues to spark
      much debate because it is fundamental to population regulation. We used temporal
      manipulations of density to explore potentially stabilizing density dependence in
      early survivorship among six local populations of a tropical damselfish
      (Dascyllus flavicaudus). Specifically, we tested the premise that spatial
      heterogeneity in the strength of temporal density dependence would reflect
      variation in density of predators, the agent of mortality. Our field
      manipulations revealed that mortality among successive cohorts of young fishes
      was density dependent at each reef, but that its strength varied by approximately
      1.5 orders of magnitude. This spatial heterogeneity was well predicted by
      variation among the six reefs in the density of predatory fishes that consume
      juvenile damselfishes. Because density dependence arose from competition for
      enemy-free space within a shelter coral, the mortality consequence of the
      competition depended on the neighborhood density of predators. Thus, the scale of
      heterogeneity in the density dependence largely reflected attributes of the
      environment that shaped the local abundance of predators. These results have
      important implications for how ecologists explore regulatory processes in nature.
      Failure to account for spatial variation could frequently yield misleading
      conclusions regarding density dependence as a stabilizing process, obscure
      underlying mechanisms influencing its strength, and provide no insight into the
      spatial scale of the heterogeneity. Further, models of population dynamics will
      be improved when experimental approaches better estimate the magnitude and causes
      of variation in strength of stabilizing density dependence.

PMID- 17536411
TI  - Abundance and size distribution dynamics of abyssal epibenthic megafauna in the
      northeast Pacific.
AB  - The importance of interannual variation in deep-sea abundances is now becoming
      recognized. There is, however, relatively little known about what processes
      dominate the observed fluctuations. The abundance and size distribution of the
      megabenthos have been examined here using a towed camera system at a deep-sea
      station in the northeast Pacific (Station M) from 1989 to 2004. This 16-year
      study included 52 roughly seasonal transects averaging 1.2 km in length with over
      35600 photographic frames analyzed. Mobile epibenthic megafauna at 4100 m depth
      have exhibited interannual scale changes in abundance from one to three orders of
      magnitude. Increases in abundance have now been significantly linked to decreases
      in mean body size, suggesting that accruals in abundance probably result from the
      recruitment of young individuals. Examinations of size-frequency histograms
      indicate several possible recruitment events. Shifts in size-frequency
      distributions were also used to make basic estimations of individual growth rates
      from 1 to 6 mm/month, depending on the taxon. Regional intensification in
      reproduction followed by recruitment within the study area could explain the
      majority of observed accruals in abundance. Although some adult migration is
      certainly probable in accounting for local variation in abundances, the slow
      movements of benthic life stages restrict regional migrations for most taxa.
      Negative competitive interactions and survivorship may explain the precipitous
      declines of some taxa. This and other studies have shown that abundances from
      protozoans to large benthic invertebrates and fishes all have undergone
      significant fluctuations in abundance at Station M over periods of weeks to
      years.

PMID- 17536412
TI  - Genetic identity determines risk of post-settlement mortality of a marine fish.
AB  - Longitudinal sampling of four cohorts of Neopomacentrus filamentosus, a common
      tropical damselfish from Dampier Archipelago, Western Australia, revealed the
      evolution of size structure after settlement. Light traps collected
      premetamorphic individuals from the water column ("settlers") to establish a
      baseline for each cohort. Subsequently, divers collected benthic juveniles
      ("recruits") at 1-3-month intervals to determine the relative impacts of post
      settlement mortality during the first three months. Growth trajectories for
      individual fish were back-calculated from otolith records and compared with
      nonlinear mixed-effects models. Size-selective mortality was detected in all
      cohorts with the loss of smaller, slower growing individuals. Three months after
      settlement, recruits showed significantly faster growth as juveniles, faster
      growth as larvae, and larger sizes as hatchlings. The timing and intensity of
      post-settlement selection differed among cohorts and was correlated with density
      at settlement. The cohort with the greatest initial abundance experienced the
      strongest selective mortality, with most of this mortality occurring between one
      and two months after settlement when juveniles began foraging at higher positions
      in the water column. Significant genetic structure was found between settlers and
      three-month-old recruits in this cohort as a result of natural selection that
      changed the frequency of mtDNA haplotypes measured at the control region. The
      extent of this genetic difference was enlarged or reduced by artificially
      manipulating the intensity of size-based selection, thus establishing a link
      between phenotype and haplotype. Sequence variation in the control region of the
      mitochondrial genome has been linked to mitochondrial efficiency and weight gain
      in other studies, which provides a plausible explanation for the patterns
      observed here.

PMID- 17536413
TI  - Biotic control of stream fluxes: spawning salmon drive nutrient and matter
      export.
AB  - Organisms can control movements of nutrients and matter by physically modifying
      habitat. We examined how an ecosystem engineer, sockeye salmon (Oncorhynchus
      nerka), influences seasonal fluxes of sediments, nitrogen (N), and phosphorus (P)
      in streams of southwestern Alaska. The purpose of this study was to investigate
      whether salmon act as net importers or net exporters of matter and nutrients from
      streams and how these roles change as a function of salmon population density. We
      measured discharge and concentrations of suspended sediments and total N and P
      every 7-14 days for up to four summers in 10 streams spanning a gradient in
      salmon densities. We statistically allocated whole-season fluxes to salmon
      activities, such as excretion and bioturbation, and to export by hydrologic
      discharge. In addition, we used counts of spawning salmon to estimate nutrient
      and matter imports by salmon to streams. Large seasonal pulses of suspended
      sediments, P, and N were associated with salmon spawning activities, often
      increasing export an order of magnitude higher than during pre-salmon levels.
      Years and streams with more salmon had significantly higher levels of export of
      sediments and nutrients. In addition, years with higher precipitation had higher
      background export of P and N. Salmon exported an average of the equivalent of
      189%, 60%, and 55% of total matter, P, and N that salmon imported in their
      bodies. The relative magnitude of export varied; salmon exported more than their
      bodies imported in 80%, 20%, and 16% across all streams and years for sediments,
      P, and N, respectively. A bioassay experiment indicated that the P exported by
      salmon is directly available for use by primary producers in the downstream lake.
      These results demonstrate that salmon not only move nutrients upstream on large
      spatial scales via their migration from the ocean and subsequent death, but also
      redistribute matter and nutrients on finer spatial scales through their spawning
      activities.

PMID- 17536414
TI  - Organization of Plethodon salamander communities: guild-based community assembly.
AB  - A long-standing goal in evolutionary ecology is to determine whether the
      organization of communities is reflective of underlying deterministic processes.
      In this study, I examined patterns of species co-occurrence among eastern
      Plethodon salamanders and determined whether they were consistent with
      predictions from a guild model of competition-based community assembly. Using a
      database of 45 species and 4540 geographic sites, I found that patterns of co
      occurrence were significantly nonrandom at both a regional and continental scale,
      and species of different size guilds were distributed more evenly in sites than
      was expected by chance. Sites with the highest species richness had consistent
      patterns of community composition, and with few exceptions, the same five species
      were present at all sites. Taken together, these results imply that larger
      Plethodon communities are assembled from simpler communities in a manner
      consistent with what is predicted through competitive mechanisms and suggest that
      stable species combinations are possible to achieve at various levels of species
      richness. These results also provide strong evidence consistent with the
      hypothesis that competitive-based community assembly is a general phenomenon in
      Plethodon and that interspecific competition is prevalent among the eastern
      species of this group.

PMID- 17536415
TI  - Functional responses: a question of alternative prey and predator density.
AB  - Throughout the study of ecology, there has been a growing realization that
      indirect effects among species cause complexity in food webs. Understanding and
      predicting the behavior of ecosystems consequently depends on our ability to
      identify indirect effects and their mechanisms. The present study experimentally
      investigates indirect interactions arising between two prey species that share a
      common predator. In a natural field experiment, we introduced different densities
      of mealworms (Tenebrio molitor), an alternative prey, to a previously studied
      predator-prey system in which paper wasps (Polistes dominulus) preyed on shield
      beetle larvae (Cassida rubiginosa). We tested if alternative prey affects
      predation on the first prey (i.e., the predator-dependent functional response of
      paper wasps) by modifying either interference among predators or the effective
      number of predators foraging on shield beetles. Presence of mealworms
      significantly reduced the effective number of predators, whereas predator
      interference was not affected. In this way, the experimentally introduced
      alternative prey altered the wasps' functional response and thereby indirectly
      influenced C. rubiginosa density. In all prey-density combinations offered, paper
      wasps constantly preferred T. molitor. This led to an asymmetrical, indirect
      interaction between both prey species: an increase in mealworm density
      significantly relaxed predation on C. rubiginosa, whereas an increase in C.
      rubiginosa density intensified predation on mealworms. Such asymmetrical outcomes
      of a fixed food preference can significantly affect the population dynamics of
      the species involved. In spite of the repeated finding of a Type III functional
      response in this system, our experiment did not reveal switching behavior in
      paper wasps. The variety of mechanisms underlying direct and indirect
      interactions within our study system exemplifies the importance of incorporating
      alternative prey when investigating the impact of a generalist predator on a
      focal prey population under realistic field conditions.

PMID- 17536416
TI  - A unified model of avian species richness on islands and continents.
AB  - How many species in a given taxon should be found in a delimited area in a
      specified place in the world? Some recent literature suggests that the answer to
      this question depends strongly on the geographical, evolutionary, and ecological
      context. For example, current theory suggests that species accumulate as a
      function of area differently on continents and islands. Species richness-climate
      relationships have been examined separately on continents and on islands. This
      study tests the hypotheses that (1) the functional relationship between richness
      and climate is the same on continents and islands; (2) the species-area slope
      depends on distance-based isolation; (3) species-area relationships differ among
      land bridge islands, oceanic islands, and continents; (4) richness differs among
      biogeographic regions independently of climate and isolation. We related bird
      species numbers in a worldwide sample of 240 continental parcels and 346 islands
      to several environmental variables. We found that breeding bird richness varies
      similarly on islands and on continents as a function of mean annual temperature,
      an area x precipitation interaction, and the distance separating insular samples
      from the nearest continent (R2 = 0.86). Most studies to date have postulated that
      the slope of the species-area relationship depends upon isolation. In contrast,
      we found no such interaction. A richness-environment relationship derived using
      Old World sites accurately predicts patterns of richness in the New World and
      vice versa (R2 = 0.85). Our results suggest that most of the global variation in
      richness is not strongly context-specific; rather, it reflects a small number of
      general environmental constraints operating on both continents and islands.

PMID- 17536417
TI  - Relationships between species richness, evenness, and abundance in a southwestern
      savanna.
AB  - Species richness and evenness are components of biological diversity that may or
      may not be correlated with one another and with patterns of species abundance. We
      compared these attributes among flowering plants, grasshoppers, butterflies,
      lizards, summer birds, winter birds, and rodents across 48 plots in the
      grasslands and mesquite-oak savannas of southeastern Arizona. Species richness
      and evenness were uncorrelated or weakly negatively correlated for each taxonomic
      group, supporting the conclusion that richness alone is an incomplete measure of
      diversity. In each case, richness was positively correlated with one or more
      measures of abundance. By contrast, evenness usually was negatively correlated
      with the abundance variables, reflecting the fact that plots with high evenness
      generally were those where all species present were about equally uncommon.
      Therefore richness, but not evenness, usually was a positive predictor of places
      of conservation value, if these are defined as places where species of interest
      are especially abundant. Species diversity was more positively correlated with
      evenness than with richness among grasshoppers and flowering plants, in contrast
      to the other taxonomic groups, and the positive correlations between richness and
      abundance were comparatively weak for grasshoppers and plants as well. Both of
      these differences can be attributed to the fact that assemblages of plants and
      grasshoppers were numerically dominated by small subsets of common species
      (grasses and certain spur-throated grasshoppers) whose abundances differed
      greatly among plots in ways unrelated to species richness of the groups as a
      whole.

PMID- 17536418
TI  - Effect of elevated CO2 on coarse-root biomass in Florida scrub detected by ground
      penetrating radar.
AB  - Growth and distribution of coarse roots in time and space represent a gap in our
      understanding of belowground ecology. Large roots may play a critical role in
      carbon sequestration belowground. Using ground-penetrating radar (GPR), we
      quantified coarse-root biomass from an open-top chamber experiment in a scrub-oak
      ecosystem at Kennedy Space Center, Florida, USA. GPR propagates electromagnetic
      waves directly into the soil and reflects a portion of the energy when a buried
      object is contacted. In our study, we utilized a 1500 MHz antenna to establish
      correlations between GPR signals and root biomass. A significant relationship was
      found between GPR signal reflectance and biomass (R2 = 0.68). This correlation
      was applied to multiple GPR scans taken from each open-top chamber (elevated and
      ambient CO2). Our results showed that plots receiving elevated CO2 had
      significantly (P = 0.049) greater coarse-root biomass compared to ambient plots,
      suggesting that coarse roots may play a large role in carbon sequestration in
      scrub-oak ecosystems. This nondestructive method holds much promise for rapid and
      repeatable quantification of coarse roots, which are currently the most elusive
      aspect of long-term belowground studies.

PMID- 17536419
TI  - [Perception and understanding chronic heart failure by the patient. The impact of
      therapeutic education on the level of knowledge of patients. About 350 cases].
AB  - Heart failure is a severe disease with a poor prognosis despite major therapeutic
      progresses achieved recently. A key factor is the high number of hospitalizations
      for heart failure, considered as being avoidable, since they are related to a
      lack of adequate management of the patients. Several therapeutic education
      programs focused on heart failure are in progress. Even though these programs aim
      at making patients an active agent managing the disease, data on patient's level
      of knowledge and experience regarding heart failure are scarce. The aim of our
      study was to analyze the patient's perception of the disease and his/her
      practices about this disease, as well as the treatments used. METHODS: we
      included 350 consecutive patients and analyzed their level of knowledge and
      experience using a questionnaire, as well as interviews performed by nurses and
      physicians. This initial assessment was followed by a second assessment after an
      8-hours course in 2 days, made by the multidisciplinary education team of R.
      Dubos hospital (including physicians, nurses, physiotherapists, dietician).
      RESULTS: in contrast to tests assessing the knowledge on the disease, which were
      in overall satisfactory, the results on the level of knowledge on treatments and
      heart failure pathways were poor. The courses improve significantly the level of
      knowledge in all domains, whatever would the age and the level of patient's
      demand for information be. The analysis of the patient's conception of his/her
      own disease reveals the lack of knowledge on the severity of heart failure.
      Frequently, the effect of treatments is considered as poorly efficient, and a
      substantial fraction of these patients have underlying depressive moods.
      CONCLUSION: the understanding of the level of knowledge and the perception of the
      patient regarding his/her disease is primordial for setting educational
      structures and programs. However, the patient's conception of the disease is
      different from care providers. It is therefore essential to assess the patient's
      conception by an educational diagnosis prior to implement adapted education
      programs, in order to improve durably the patient's knowledge, at every age.

PMID- 17536420
TI  - [Variations of radiation dosage delivered to patients undergoing interventional
      cardiological procedures. A monocentric study 2002-05].
AB  - X-ray exposure of patient during coronary angiography (CA) and percutaneous
      transluminal coronary angioplasty (PTCA) may have some deleterious effects. The
      dose area product (DAP), related to the effective dose, is a measure of
      stochastic risk and a potential quality indicator. The aim of our study was to
      assess radiation exposure of patients in a large series of "real life"
      interventional cardiac procedures. We evaluated DAP and Fluoroscopy time (t)
      during CA and/or PTCA in 3600 consecutive patients from 2002 to 2005. Procedures
      were performed by five experienced physicians, using successively femoral and
      radial techniques. DAP and t significantly correlated (r = 0.73; p < 0.0001).
      Median [25th-75th percentiles] values for DAP and for t were 63 [40-101] Gy.cm2
      and 6.3 [4-10] min for CA, 100 [62-178] Gy.cm2 and 14.0 [9-22] min for elective
      PTCA, and 141 [90-219] Gy.cm2 and 15.7 [11-23] min for CA immediately followed by
      ad hoc PTCA, respectively. Differences between operators ranged from 50% (CA) to
      70% (PTCA) for both DAP and t (p < 0.001). Moving from the femoral to the radial
      approach resulted in a 1.5 to 2-fold increase in DAP in 2002 (p < 0.001). DAP and
      t then decreased toward the european DIMOND reference values (in 2005: 53.4
      Gy.cm2 and 5.5 min for CA, 104.64 Gy.cm2 and 13.1 min for elective PTCA, 128.4
      Gy.cm2 and 13.6 min for ad hoc PTCA). In conclusion, radiation exposure to
      patients and staff are strongly dependent on operators, time course, and the
      arterial access, due in part to the learning curve for radial approach. The
      enhanced knowledge of radiation dose is the first step of a radiation dose
      reduction program, likely to minimize patient and operator radiation hazards in
      interventional cardiology. Definition of national reference values for DAP and
      fluoroscopy time would be helpful for appropriate comparisons.

PMID- 17536422
TI  - [Early detection of myocardial disease in young patients with Becker's muscular
      dystrophy asymptomatic from the cardiac point of view: value of myocardial
      doppler tissue imaging].
AB  - Becker's muscular dystrophy is an X-linked hereditary disorder characterised by
      progressive muscle weakness and possible cardiac disease. Cardiac involvement is
      assumed to be rare in young patients. Early diagnosis could lead to earlier
      treatment at an infra-clinical stage of the disease. The object of the study was
      to evaluate systolic and diastolic cardiac function of young patients with
      Becker's disease by echocardiography and using Doppler tissue imaging.
      Consecutive patients under 20 years of age with Becker's disease confirmed
      genetically were included and compared with paired normal subjects.
      Subendocardial and subepicardial myocardial velocities were obtained by Doppler
      tissue imaging and the corresponding velocity gradients were measured. Twelve
      patients were included (17.4 +/- 2.5 years). None of them had disabling muscle
      disease. No significant difference was observed from normal subjects with respect
      to: ventricular dimensions, wall thickness, fractional shortening, E/A ratio
      measured by transmitral Doppler. Nevertheless, patients with Becker's disease had
      lower systolic and diastolic intra-myocardial velocity gradients: 2.2 +/- 1.1 vs.
      4.7 +/- 2.4 s(-1), p = 0.006, and 3.6 +/- 2.0 vs. 5.6 +/- 1.3 s(-1), p = 0.048,
      respectively, compared with the control group. These results show that myocardial
      disease is possible in patients with Becker's muscular dystrophy under the age of
      20. Myocardial Doppler tissue imaging is a sensitive method for detecting these
      early abnormalities and should be recommended in the young patients.

PMID- 17536421
TI  - [Treatment of intrastent restenosis by drug eluting stents: experience from one
      cardiology centre].
AB  - Many interventional treatments have been proposed for intrastent stenosis, in
      particular by drug-eluting stents, with encouraging results. The aim of this
      study was to assess the clinical outcome of patients with restenosis of an
      ordinary uncovered stent treated by a drug eluting stent in a prospective series.
      The register included 43 patients (50 intrastent restenoses) treated by a drug
      eluting stent (Cypher or Taxus). The restenosis lesion was focal in 32% of cases
      with an average length of 14.8 +/- 8 mm and diameter inferior to 2.5 mm in 48% of
      cases. A Cypher stent was implanted in 44% of cases and a Taxus stent in 56% of
      cases. After an average follow-up of 6.7 +/- 1.3 months, the major adverse
      cardiac event rate was 9.3%. It included one transmural infarct in a patient, due
      to stent thrombosis, and symptomatic restenoses in 3 patients (clinical
      restenosis rate: 7%). An angiographic control was performed in 15 patients (35%)
      identifying focal restenosis at the exit of the stent in the 3 symptomatic
      patients. As in previously reported studies, these results show that with well
      conducted platelet antiaggregant therapy, the treatment of intrastent restenosis
      with a drug eluting stent is effective with a low rate of adverse cardiovascular
      events which compares favourably with previously proposed techniques of
      management.

PMID- 17536423
TI  - [Recomendations on management of left ventricular hypertrophy in athletes. The
      Working Group of Sports Cardiology of the French Society of Cardiology].

PMID- 17536424
TI  - [Revascularisation of unprotected left main coronary artery disease: an update].
AB  - Coronary bypass grafting is the reference treatment of unprotected left main
      coronary disease. Nevertheless, the experience of invasive cardiologists and the
      introduction of active stents make angioplasty possible in selected cases. Only
      the results of controlled clinical trials (SYNTAX trial currently under way) will
      enable physicians to choose the most appropriate method of revascularisation for
      their patients.

PMID- 17536425
TI  - [Subclinical hypothyroidism: a cardiovascular risk factor?].
AB  - Although patent hypothyroidism is clearly associated with increased
      cardiovascular risk, the relationship between infraclinical hypothyroidism and
      cardiovascular disease remains controversial though probable. This relationship
      is mediated by the traditional risk factors (lipids, hypertension), by changes in
      parameters of inflammation and haemostasis, and by a direct effect of thyroid
      hormones on the vessel wall. The authors review the epidemiological evidence and
      the mechanisms underlying the association between infraclinical hypothyroidism
      and cardiovascular risk and the therapeutic implications of this association.

PMID- 17536426
TI  - [Very late intrastent thrombosis--at 27 months!].
AB  - Interrupting platelet antiaggregant therapy in coronary patients treated by
      stenting exposes them to the risk of cardiac complications. The risk of acute
      thrombosis of the stent is well known but late intrastent thrombosis is less
      common and mainly observed with drug eluting stents. The authors report the case
      of a 54 year old man who had thrombosis of an ordinary stent implanted 27 months
      previously which occurred in the immediate post-operative period after repair of
      an inguinal hernia. The interruption of platelet antiaggregant therapy was
      relayed by flurbiprofen in accordance with recommendations of scientific
      societies. After a review of the literature, the authors discuss late stent
      thrombosis and interruption of platelet aggregant therapy in coronary patients
      before non-cardiac surgery.

PMID- 17536427
TI  - [The ictal bradycardia syndrome: a case report and review of the literature].
AB  - Epilepsy is a rare cause of sinus node dysfunction which should be recognised.
      The authors report the case of a 55 year old woman with refractory epilepsy who
      had sinus arrest during her epileptic fits. After excluding a possible
      interaction by long-term Carbamazepine treatment, the diagnosis of the Ictal
      bradycardia syndrome was made in view of the simultaneous occurrence of severe
      bradycardia and epileptic activity recorded on electro-encephalography. Sudden
      death being more common in epilepsy, effective treatment of conductive cardiac
      abnormalities is essential. The refractory nature of the epileptic fits led to
      the implantation of a permanent pacemaker in this case.

PMID- 17536428
TI  - T-tubules: a key structure of cardiac function and dysfunction.
AB  - The sarcolemmal membrane of mammalian ventricular cardiomyocytes are
      characterised by the presence of invaginations called transverse tubules (T
      tubules) which constitute a network, the transverse tubule system. T-tubules
      occur at the Z line as transverse elements with also longitudinal extensions.
      While the existence of T-tubules has been known since a long time, recent studies
      have suggested their structure and function can be more complex than previously
      believed. Many of the proteins involved in excitation-contraction coupling
      process are concentrated within the T-tubular network, suggesting T-tubules are a
      highly specialized membrane system. Thus, T-tubules are a key determinant of
      cardiac cell function. The fundamental role of T-tubules is emphasized by changes
      in their structure and protein expression occurring during pathologies such as
      cardiac hypertrophy and heart failure. This review summarizes recent studies
      which highlight the key-role of the T-tubules in the regulation of cardiac
      function. Changes observed in pathological conditions are also discussed.

PMID- 17536429
TI  - Opioids and myocardial reperfusion injury.
AB  - It is well-established that reperfusion is the major method of salvaging ischemic
      myocardium following prolonged coronary artery occlusion, although the idea of
      reperfusion injury remains controversial. Moreover, more recent evidence strongly
      suggests that reperfusion per se is thought to result in further damage to the
      myocardium and blood vessel endothelium by various biochemical and physical
      factors including a burst of oxygen-derived free radicals (ROS), cellular or
      mitochondrial calcium overload and shear stress, to name a few. This has been
      termed lethal reperfusion injury. It has become increasingly evident that
      strategies in which interventions are administered during the early stages of
      reperfusion produce a reduction in reperfusion-mediated damage primarily by
      reducing massive calcium overload or by altering the intracellular milieu (pH,
      osmotic stress, etc.) and ROS release upon reperfusion. Furthermore, it is
      apparent that activation of blood borne elements such as neutrophils and
      macrophages and factors released by these cells such as cytokines may be
      responsible for a continuing expansion of infarction in the hours or even days
      following timely reflow and that inhibiting these factors may attenuate
      reperfusion injury. The present review will focus on the effect of endogenous and
      exogenous opioids on ischemic and reperfusion injury since these compounds are
      routinely used in the surgical arena and may have unappreciated cardioprotective
      effects in this subset of patients. Particular emphasis will be on the role of
      opioids in reperfusion injury and their relationship to the newly discovered
      phenomenon of postconditioning.

PMID- 17536430
TI  - Cardiac myosin-binding protein C in the heart.
AB  - Understanding the structural and functional role of cardiac myosin-binding
      protein C in the heart is clinically relevant, as cMyBP-C gene mutations are a
      widely recognized cause of familial hypertrophic cardiomyopathy. Our knowledge
      about this protein considerably improved over the past decade. This review
      outlines several studies, which highlight the role of cardiac myosin-binding
      protein C and its phosphorylation in the heart in health and disease. Arch

PMID- 17536431
TI  - Lessons from the silicosis and asbestosis mass tort scams.

PMID- 17536432
TI  - The cost of doing business: who is paying their share?

PMID- 17536433
TI  - Anti-kickback laws.

PMID- 17536435
TI  - Witnessing a metamorphosis of medicine at MU.

PMID- 17536434
TI  - Highlights of the AMA's 2006 interim meeting.

PMID- 17536436
TI  - What did you say? Pump up the volume: noise induced hearing loss in the young.

PMID- 17536438
TI  - The future of dermatology: challenges and opportunities.

PMID- 17536437
TI  - Judge sides with docs against insurance companies.

PMID- 17536439
TI  - Common sports-related dermatologic infections.
AB  - All athletes have an increased risk of cutaneous infections. In both team and
      individual sports the skin is exposed to a range of infectious organisms. While
      effective therapies exist, preventive measures can decrease outbreaks of most
      sports-related dermatologic infections. This article highlights common
      dermatologic infections of the athlete, their prevention and treatment.

PMID- 17536440
TI  - Effects of chemotherapy on skin and hair.
AB  - Skin and hair are both notable and noticeable accessory targets of chemotherapy
      and can become a point of discussion when your patient asks, "Is this problem
      happening because of my chemo?" This article will attempt to assist physicians in
      recognizing and answering this question.

PMID- 17536441
TI  - An overview of cutaneous mosaicism.
AB  - Cutaneous mosaicism is a poorly understood but relatively common dermatological
      finding. This paper reviews basic concepts of mosaicism as well as common and
      rare mosaic skin disorders.

PMID- 17536442
TI  - Psychogenic parasitosis: a therapeutic challenge.
AB  - Psychogenic parasitosis is a debilitating disorder that is typically easy to
      recognize and difficult to treat. Some of these patients will have a shakable
      belief in infestation, while others will have a true delusion. Primary care
      physicians and dermatologists can play an important role in evaluating and
      categorizing these patients, initiating treatment, and helping them to get the
      psychiatric care that they need.

PMID- 17536443
TI  - Teledermatology in Missouri and beyond.
AB  - The practice of teledermatology has grown considerably in rural and frontier
      areas where access barriers exist. Live-interactive and store-and-forward
      modalities are used, either alone or in combination (hybrid model). Research has
      shown that the diagnoses made and management recommended during teledermatology
      interactions are in concordance with in-person diagnosis and treatment. Many
      patients worldwide have limited access to expert dermatological care and the
      current technology is increasingly offering access for these patients.

PMID- 17536444
TI  - Herpes simplex virus: it's more than a cold sore.
AB  - Herpes simplex virus (HSV) is a common office problem and may be trivialized as
      "just a cold sore." HSV infections may cause great concern to the otherwise
      healthy patient due to psychosocial issues and may lead to morbidity and
      mortality in certain populations. This article discusses clinical presentation,
      diagnosis, and management of orolabial/genital herpes and presents answers to
      questions frequently posed to primary care providers and specialists.

PMID- 17536445
TI  - The art of tattooing and the science of tattoo removal.
AB  - In recent years there has been a dramatic increase in body tattooing among all
      socioeconomic groups. This paper describes the techniques of tattooing, the
      public health implications, methods for removal of tattoos.

PMID- 17536446
TI  - The great Perry Nichols secret escharotic cancer treatment.
AB  - The Dr. Nichols Sanatorium had a life of 60 years (1896-1956) and achieved its
      greatest success in Savannah, Missouri (1912-1956). More than 70,000 patients
      from every state and several foreign countries were treated for skin, mucosal and
      breast cancer. This paper will detail the author's investigation into why Nichols
      with his escharotic (caustic) method did not make the discoveries later achieved
      by Frederick Mohs, MD, of Mohs Chemosurgery fame.

PMID- 17536447
TI  - The painful bladder: urinary tract infection and interstitial cystitis in women.
AB  - Irritative voiding symptoms in women are most often due to uncomplicated urinary
      tract infection. A cost-effective approach to the treatment of urinary tract
      infections is a reasonable first step. However, in patients who have persistent
      or frequently recurrent symptoms, a more thorough evaluation is warranted. These
      women may be found to have interstitial cystitis, requiring further evaluation.
      While interstitial cystitis remains a difficult disease to treat, a multi
      modality therapy provides excellent symptom relief.

PMID- 17536448
TI  - The role of robotics in surgery: a review.
AB  - Within the last decade, robotic-assisted surgery has emerged with the promise of
      extending the benefits of minimally invasive surgery to virtually every surgical
      specialty while decreasing patient morbidity and improving postoperative
      outcomes. This article reviews the history, development, current and future
      applications of robotics in surgery, and its increasing prevalence in the field
      of urology.

PMID- 17536449
TI  - [Applied anatomy study on the lateral wall of sphenoid sinus under transnasal
      endoscope].
AB  - OBJECTIVE: To provide transsphenoidal endoscopic surgery with the anatomic
      reference through anatomic study on the lateral wall of sphenoid sinus under
      transnasal endoscope. METHOD: The dissection of the lateral wall of sphenoid
      sinus were performed on 10(20 sides) damp cadaveric heads of Chinese adults via
      transsphenoidal approach. The anatomic relationship of the lateral wall of
      sphenoid sinus and its adjacent structures were observed. The distance and angle
      from the bony prominence of optic canal and internal carotid artery to the
      columella nasi and midline of sellar floor were measured by ruler and protractor
      respectively. RESULT: From the study of endoscopic anatomy, the specific
      structure of optic canal and internal carotid artery were found, and the lateral
      wall of the cavernous sinus could be exposed by tracing the internal carotid
      artery. The mean distance from the midpoint of the medial wall of optic canal
      orbital aperture and the anterior bony prominence of internal carotid artery to
      the columella nasi were (75. 33 +/- 5. 59)mm and (81. 02 +/- 5. 29) mm
      respectively, to the midline of sellar floor were (5. 81+/- 1. 52)mm and (5. 53
      +/- l. 47)mm respectively. The angle from the midpoint of the medial wall of
      optic canal orbital aperture to columella nasi was (53.4 +/- 4. 1) degrees.
      CONCLUSION: Taken the columella nasi and midline of sellar floor as the reference
      points, the anatomic observation and measurement under endoscope via
      transsphenoidal approach can provide a guide for surgeons.

PMID- 17536450
TI  - [Acoustic rhinometry in the diagnosis of children with obstructive sleep apnea
      hypopnea syndrome].
AB  - OBJECTIVE: To explore the role of acoustic rhinometry in the diagnosis of
      children with obstructive sleep apnea-hypopnea syndrome (OSAHS). METHOD: Thirty
      six patients with OSAHS were measured with acoustic rhinometry before and 1 month
      after adenoidectomy. Twenty patients with adenoidectomy were measured before and
      after operation, the changes in volume recorded by acoustic rhinometry were
      compared with the adenoid volume obtained by the method of "drain off the water".
      RESULT: The volume of nasopharynx of adenoid removal patients was significantly
      bigger than that of before operation. The adenoid volume of 20 patients obtained
      by the method of "drain off the water" was bigger than the calculated changes in
      nasopharynx volume recorded by acoustic rhinometry, however, they were found to
      be significantly interrelated. CONCLUSION: Acoustic rhinometry is a better method
      to calculate the size of adenoid in children with OSAHS and it could become a
      routine examination before adenoidectomy.

PMID- 17536451
TI  - [The value of cyclooxygenase-2 to predict the effect of radiotherapy in
      nasopharyngeal carcinoma].
AB  - OBJECTIVE: To investigate the relation between the expression of COX-2 protein
      and the effect of radiotherapy, estimate the value of COX-2 in predicting the
      effect of radiotherapy in patients with nasopharyngeal carcinoma,provide
      theoretical basement for establishing characteristic project of treatment and
      raising curative effect and life quantity. METHOD: The expression of COX-2
      protein was examined in 30 radiosensitive and 30 radioresistant poorly
      differentiated NPC by immunohistochemical staining (SP method) before
      radiotherapy. The relation between the expression of COX-2 and the effect of
      radiotherapy was analyzed. RESULT: The positive rate of COX-2 protein expression
      was 61. 67% in NPC tissues, there was statistical difference( P <0. 01) of the
      positive rate between the 86. 67 % of 30 radioresistant and 36. 67 % of
      radiosensitive NPC tissues. The intensity of COX-2 protein expressions showed
      statistical difference( P <0. 05),too. Based on the expression of COX-2, the
      effect of radiotherapy, sensitivity, specificity, accuracy, positive predictive
      value, negative predictive value, false positive and false negative were
      predicted as follows: 86. 67Y, 63. 33% ,75. 00%, 70. 27% ,82. 61% ,36. 67% and
      13. 33 , respectively. CONCLUSION: COX-2 expression may serve as a marker in
      predicting the response to radiotherapy in NPC. According to the expression of
      COX-2, the sound treatment scheme can be selected.

PMID- 17536452
TI  - [Experiences of nasal reconstruction with forehead flap: reports of 13 cases].
AB  - OBJECTIVE: To present the experience of nasal reconstruction with forehead flap.
      METHOD: nasal reconstruction with forehead flap were applied in eight nasal
      carcinoma cases after operation and 5 nasal trauma cases with defects. RESULT:
      These forehead flaps were alive in all patients, all incision healed in I stage,
      no post operative complications were found. The shapes of nose were satisfactory,
      there were no recurrence of tumor during 1 to 17 year follow up. CONCLUSION: The
      method can be clinically applied for its simple procedure, reliable flap's blood
      supply, high survival rate and satisfied result.

PMID- 17536454
TI  - [A clinical study of dacryocystorhinostomy per nasal endoscope guided by endo
      ophthalmic optical fiber].
AB  - OBJECTIVE: To get a method of dacryocyst allocation for dacryocystorhinostomy per
      nasal endoscope. METHOD: The dacryocyst of 7 chronic dacryocystitis cases(8 eyes)
      were located through nasal cavity guided by endo-ophthalmic optical fiber.
      RESULT: All the 7 patients got successful operations, the bleeding was 10-20 ml
      during the operation , postoperative recovery was good, no infection occurred.
      Five patients received operations twice, all of them were detained anaesthetic
      tubes for 3 to 6 months, dacryocyst rinsing were conducted once per month after
      extubation. No obstructions and complications occurred after one year follow up.
      CONCLUSION: Endo ophthalmic optical fiber can be used to locate dacryocyst in
      dacryocystorhinostomy per nasal endoscope.

PMID- 17536453
TI  - [Clinical significance of HIF-1 alpha,VEGF and VEGF-C expression in papillary
      thyroid carcinoma].
AB  - OBJECTIVE: To evaluate clinical significance of HIF-1 alpha,VEGF and VEGF-C
      expression in papillary thyroid carcinoma. METHOD: HIF-1a,VEGF and VEGF-C
      expression were detected by immunohistochemical method in 73 patients of
      papillary thyroid carcinoma(group I ), 32 patients of thyroid adenoma(group II)
      and 35 patients of nodular goiter(group II ) respectively. RESULT: The expression
      of HIF-1 alpha in group I (75. 3%) was higher than that in group I (18. 8% ) and
      in group III (14. 3%) ( P <0. 01). The similar results were also observed about
      VEGF and VEGF-C. The positive rate of VEGF and VEGF-C (72. 6% and 65. 8%) in
      group I were markedly increased, compared with that in group II (18. 8% and 15.
      6%, P<0. 01) or III (20. 0% and 11. 4%, P <0. 01) . In carcinoma patients with
      lymph node metastasis, the higher expressions of HIF-1a,VEGF and VEGF-C were
      observed as compared with those without metastasis( P <0. 05,respectively). VEGF
      and VEGF-C expression had a positive correlation with HIF-1 alpha ( P <0. 05).
      CONCLUSION: In papillary thyroid carcinoma, HIF-1 alpha, VEGF and VEGF-C
      expression are significantly increased. Furthermore,VEGF and VEGF-C expression
      may be regulated by HIF-1 alpha, involving in the process of cancer cell
      spreading to lymph nodes.

PMID- 17536455
TI  - [Clinical use of acoustic rhinometry guiding radiofrequency to treat nasal
      obstruction].
AB  - OBJECTIVE: To investigate the value of acoustic rhinometry in treating patients
      with nasal obstruction by radiofrequency(RF). METHOD: The clinical results of 46
      nasal obstruction cases treated by RF were analyzed. The therapy area were
      determined by acoustic rhinometry. RESULT: Pretherapy: mean nasal cross-sectional
      area (NMCA) (0. 37+/-0. 16)cm(2) , the front part of inferior nasal concha
      minimal cross-sectional area (MCA) (1. 10+/-0. 17)cm(2) , volume of nasal
      cavity(NV) (5. 76 +/-2. 81) cm(3), nasal resistance(NR) (5. 96 +/- 2. 24) kPa x
      s/L. Post therapy: NMCA(0. 68+/-0. 18)cm, MCA(1. 76+/-0. 19)cm(2), NCV (9. 10+/
      2. 10)cm(3), NR(2. 42+/-0.86) kPa x s/ L. For 46 cases, there were remarkable
      improvements between pretherapy and post therapy ( P <0. 05). Twenty-seven cases
      were cured, 19 cases were improved, total effectiveness rate were 100%.
      CONCLUSION: RF therapy guided by acoustic rhinometry may help determine the
      therapy area and improve the effectiveness.

PMID- 17536456
TI  - [The clinic anatomy of operation on pterygopalatine fossa through nasal cavity
      under endoscope].
AB  - OBJECTIVE: To provide anatomic data of pterygopalatine fossa(PPF) for endoscopic
      PPF surgery. METHOD: Fifteen wet adult skull specimen fixed in 10% formaldehyde
      were studies. From center the skulls were sawed, the middle and inferior
      turbinate were resected, the anterior and posterior ethmoid sinuses were
      resected. Then after punch out perpendicular part of palatine bone and posterior
      wall of maxillary,the pterygopalatine fossa were showed and some related
      measurements were made. RESULT: This pathway can lead to a good view of
      pterygopalatine fossa. The main soft structures in PPF were maxillary artery and
      nerve with their branches. The diameter of artery branches was smaller than 3 mm.
      CONCLUSION: The endoscopic PPF surgery is safe and practical from the anatomic
      data.

PMID- 17536457
TI  - [The effects on nasal mucociliary clearance system of excising partial inferior
      turbinectomy with HUMMER or microwave].
AB  - OBJECTIVE: To study the effects of excising partial inferior turbinectomy with
      powered sinus clissector (HUMMER) and microwave on nasal mucociliary clearance
      system, and offer the theoretical foundation to choose rational operational
      technique. METHOD: The patients of HUMMER group were excised partial inferior
      turbinectomies with HUMMER and the microwave group with microwave, each group
      included 20 patients. Ten patients without nasal disease were selected as
      control. Every case was drawn nasal mucus of inferior turbinectomy
      preoperatively, three months and six months after surgery. Five control cases
      selected randomly were drawn specimens. The specimens were observed under light
      microscope and scanning electron microscope. Every case accepted saccharin test
      before the specimen was drawn. All data were analyzed with paired sample t-test
      and analysis of variance. RESULT: (1) Saccharin test: MTR(mucociliary transport
      rate)for before surgery, three months after surgery and six months after surgery
      with HUMMER were (3.63+/-0.57) ,(3. 76+/-0.43) and (6. 09+/-1. 19)mm/min,
      respectively. MTR for six months after surgery significantly increased compared
      with that before surgery and three months after surgery(both P <0. 01). MTR for
      three months after surgery and six months after surgery with microwave were (3.
      96+/-0. 40)and (3. 95+/-0. 32)mm/min,respectively. MTR for three months and six
      months after surgery both significantly increased compared with that of controls
      (both P <0. 01). MTR for six months after surgery with microwave significantly
      increased compared with that with HUMMER ( P <0. 01). (2) Observation of Light
      microscope and scanning electron microscope: Before surgery with HUMMER and with
      microwave, goblet cells increased in nasal mucous epithelial of patients. The
      cilia changes included fracture, disorder, deletion and confluence. Thickness and
      size of cilia were not coincident. Partial nasal mucous epithelial metaplasis
      from pseudostratified ciliated columnar epithelium to simple cuboidal epithelium.
      Nasal mucous epithelia regenerated to pseudostratified ciliated columnar
      epithelium after surgery with HUMMER, which mainly coincided with normal nasal
      mucociliary system. Nasal mucociliary epithelial regenerated little after surgery
      with microwave. There were squamous epithelial metaplasia on nasal mucus and
      serious deletion of cilia. CONCLUSION: The surgery of excising partial inferior
      turbinectomy with HUMMER has obvious advantage in protecting and recovering
      physiological function of nasal cavity.

PMID- 17536458
TI  - [Diagnosis and treatment of nasal sinus osteoma].
AB  - OBJECTIVE: To discuss the clinical characteristic and surgical treatment of nasal
      sinus osteoma. METHOD: Fifty-one cases with nasal sinus osteoma were diagnosed by
      nasal sinus X ray or CT scan. All of these osteoma patients were cured by
      surgical resection. Supraorbital Lynch approach were applied in forty-two cases,
      lateral rhinotomy Moure approach in 4 cases, Caldwell-Luc approach in 3 cases and
      Dandy approach that combined with cranium and facial route in 2 cases. RESULT:
      Operative incisions in all cases healed in 1 period, no complications such as
      brain spinal fistula occurred. All cases were followed up for 6 months to 5
      years, there were no recurrence of osteomas and occurrence of mucus cysts.
      CONCLUSION: Osteomas in nasal sinus grow slowly. X ray or CT scan is helpful to
      confirm the diagnosis and choose the surgical approach reasonably.

PMID- 17536459
TI  - [Effects of ischemia on olfactory bulb in rats].
AB  - OBJECTIVE: To observe the olfactory bulb's morphological change after ischemic
      injury in rats, and explore the role of vascular factor in olfactory disorders.
      METHOD: Forty adult SD rats (weighting 250-300 g) were used, 30 of which were
      treated with permanent bilateral occlusion of both common carotid arteries, and
      the others were served as the control. The olfactory bulbs were carefully taken
      out on the 1st week, 4th week, 2nd month post operation, respectively, then
      observed the morphological changes by light microscopy. The ultra structure of
      cells in olfactory bulbs were also observed by transmission electron microscope.
      RESULT: In rats with permanent bilateral occlusion of both common carotid
      arteries, the vascular pattern changed and the cell number decreased in olfactory
      bulbs by light microscopy. In the 1st week group, the mitral cells' mitochondria
      injury and metamorphism were found. In the 4th week group, the microvascular
      paramorphia, lipofuscin in mitral cells and metamorphic nerve fibers were found
      by transmission electron microscope. CONCLUSION: Ischemia could injure the neuron
      and nerve fiber. This may be one of the reasons of olfactory disorders.

PMID- 17536460
TI  - 'Freedom' act is too effective for its own good.

PMID- 17536461
TI  - Shingles.

PMID- 17536462
TI  - Marketing offensive?

PMID- 17536463
TI  - Health visitor cuts affecting vulnerable families.

PMID- 17536464
TI  - A growing concern.

PMID- 17536465
TI  - Service issues.

PMID- 17536466
TI  - Natural resources.

PMID- 17536468
TI  - Volunteering as a community mother--a pathway to lifelong learning.
AB  - This paper describes a study that was undertaken to investigate the effects of
      participating in a community volunteering programme (the Community Mothers
      Programme) on volunteers (Community Mothers). The aim of the study was to
      investigate if volunteering in this programme acted as a pathway to lifelong
      learning; did the volunteers recognise the learning of new knowledge and/or
      skills, and did their participation in the programme trigger them to progress to
      further education in other settings? A self-administered questionnaire method was
      used for data collection: 115 questionnaires being distributed to volunteers,
      with a response rate of eighty-two (71 per cent). Findings show that the majority
      of the respondents cited the learning of new knowledge and/or skills as a result
      of their participation in the Community Mothers Programme. Learning appeared to
      stem from the various training and activities, suggesting an educational process
      within the volunteer setting. Findings also show that the majority of respondents
      had progressed to further education. In this instance, therefore, volunteering
      did appear to act as a pathway to lifelong learning.

PMID- 17536469
TI  - The emotional wellbeing of Bangladeshi mothers during the postnatal period.
AB  - There have been significant studies commenting on the postnatal experience and
      the emotional well-being of mothers following the birth of their child. This
      paper focuses on the emotional well-being and health beliefs of Bangladeshi
      mothers during this period. An attempt was made to understand if postnatal
      depression was recognised, how it was interpreted and to explore the effect it
      has on the well-being of the mother, her family and the wider community. A
      qualitative approach was used to explore the values and views of the mothers by
      means of a focus group interview. Ten mothers who resided in Wales and were
      brought up within a Muslim community participated in the study. Findings suggest
      that when mothers experienced emotional issues they sought the support of their
      family, friends and religious leaders, and, although familiar with some primary
      care services, they were not always their first point of contact. It is proposed
      that health visitors could discuss their role, particularly in relation to
      perinatal mental health, with the Bangladeshi mothers. This may help the mothers
      to access support and services. It is important for health visitors to understand
      the significance of cultural diversity and the competing interpretations of
      postnatal depression and also to recognise why mothers might seek alternative
      methods to manage their health during the ante and postnatal period.

PMID- 17536470
TI  - Application of health equity audit to health visiting.
AB  - Equitable access to health care services is an important driver to improve
      health. The link between socio-economic status and ill health has long been
      established and yet some population groups are still disadvantaged in accessing
      services. Health equity audit is a tool that enables the identification and
      redistribution of resources on the basis of need. Within the former Charnwood and
      North West Leicestershire Primary Care Trust, a health equity audit was
      undertaken to ensure the provision of health visiting resource was based on the
      health needs of the population. Equity was assessed utilising neighbourhood-based
      indices of multiple deprivation (IMD) and hours of health visiting activity.

PMID- 17536471
TI  - Mastitis.

PMID- 17536472
TI  - Evidence-based salaries.

PMID- 17536473
TI  - Identity as a moderator of gender differences in the emotional closeness of
      emerging adults' same- and cross-sex friendships.
AB  - Closeness is an integral aspect of friendships, and males and females differ in
      their closeness experiences within these relationships. However, identity
      development and friendship type (e.g., same-sex versus cross-sex friendships) may
      moderate these gender differences. In an attempt to clarify the relationships
      among gender, identity, and friendship closeness, the current study examined
      gender and identity associations with reported emotional closeness in emerging
      adults' same- and cross-sex friendships. Responses from 181 college
      undergraduates (89 males and 92 females) indicated similar levels of emotional
      closeness reported for same- and cross-sex friendships. Results also indicated
      overall identity commitment and friendship identity commitment associations with
      same-sex friendship closeness. Examination of closeness reports for cross-sex
      friends revealed a significant association with overall identity commitment for
      emerging adult males. A significant association was not indicated for emerging
      adult females. The associations between identity and emotional closeness in same
      sex friendships and male cross-sex friendships support previous studies that
      report differences in the role of these relationships for emerging adult males
      and females. Findings are discussed in terms of understanding the gender and
      identity differences in emerging adults' reports of friendship closeness.

PMID- 17536474
TI  - Rural adolescent aggression and parental emotional support.
AB  - Preliminary research findings suggest important distinctions between rural and
      urban adolescent aggression risk and protective factors. Despite these
      potentially important differences, most of the existing research on adolescent
      aggression has utilized urban samples. The current study examines the direct
      association between parental emotional support and rural adolescent aggression,
      and whether adolescent psychopathology and substance abuse mediate this
      association. Multi-method measurement (self-report, parent report, and behavioral
      observations) were employed in measuring aggression and emotional support
      variables with rural, nonadjudicated adolescents (N=62) and their mothers or
      stepmothers. Results indicated that parental emotional support has an indirect
      influence on adolescent aggression. Adolescent substance abuse was completely
      mediated by adolescent grade-point average, indicating no significant direct
      impact on aggression. Adolescent psychopathology significantly mediated the
      relationship between parental emotional support and adolescent aggression.
      Particular items contributed substantially to this mediating association, making
      certain characteristics, rather than a specific diagnosis, relevant to
      psychopathology's mediating impact. These characteristics include cognitive
      perception of others as critical or hostile, emotional anxiousness in social
      situations, and behavioral persistence in social interactions despite these
      perceptions.

PMID- 17536475
TI  - Validation of the multiple language versions of the Hopkins Symptom Checklist-37
      for refugee adolescents.
AB  - The objective of this study is to provide preliminary psychometric properties of
      the Hopkins Symptom Checklist-37 (HSCL-37A) for refugee adolescents. The HSCL-37A
      is a modification of the well-known HSCL-25 and assesses symptoms of
      internalizing and externalizing problems that have been associated with reactions
      to trauma. Four independent heterogeneous samples (N=3890) of unaccompanied
      refugee minors, immigrants, and native Dutch and Belgian adolescents were
      assessed at school. The confirmative factor analyses, per language version,
      support the two-factor structure of internalizing and externalizing behavior. The
      total and subscales show good internal consistency and acceptable test-retest
      reliability in spite of the heterogeneous sample populations. The construct,
      content, and criterion validity of the HSCL-37A were also examined and found to
      be good. The findings of this study suggest that the HSCL-37A is a reliable and
      valid instrument to be used among culturally diverse refugee adolescents to
      assess emotional distress and maladaptive behaviors.

PMID- 17536476
TI  - Nexus aliquis: in pursuit of efficacy, resilience, and full potential.
AB  - This work examines the integral nexus of teacher and student, suggesting that
      efforts, resources, and human resource functions can and should intentionally
      focus on the relationship as paramount. Other aspects of learning potential are
      de minimus if teacher-student interaction is not efficient and affective. School
      leadership, learning paradigms, and hiring should focus on student-centered
      approaches that require collective efficacy, teachers becoming significant others
      in their student's lives, and development of resiliency in student intellectual
      attitudes. Reframing of the human resource function to recruit and retain life
      enhancing educators who initiate rigorous and relevant learning, facilitate
      mastery, and incite intellectual curiosity for its own sake within students is
      called for. A suggested administrative interview and training examples are
      provided.

PMID- 17536477
TI  - Setting goals, solving problems, and seeking social support: developing
      adolescents' abilities through a life skills program.
AB  - The Going for the Goal (GOAL) program is designed to teach adolescents life
      skills. There have been few efforts to assess whether the skills that GOAL is
      designed to teach are being learned by adolescents involved in the program. The
      purpose of this study was to examine the impact of GOAL on the acquisition of
      skills in the areas of setting goals, solving problems, and seeking social
      support. Interviews were conducted with twenty adolescents. Those who
      participated in GOAL reported that they had learned how to set goals, to solve
      problems effectively, and to seek the appropriate type of social support.

PMID- 17536478
TI  - A longitudinal study on transactional relations between parental marital distress
      and adolescent emotional adjustment.
AB  - Using a cross-lagged effect model with 3 waves of data from a 6-year longitudinal
      study with 3-year intervals, transactional relations between parental marital
      distress and adolescent emotional adjustment were examined. The sample consisted
      of 531 parent-adolescent dyads. Results showed that marital distress as reported
      by parents and emotional adjustment as reported by adolescents were reciprocally
      related in a transactional model over time. This was principally true for girls
      and for late adolescents and young adults. For older adolescent girls, an almost
      full transactional model was found, whereas associations between marital distress
      and emotional adjustment were less strong for younger girls and were absent for
      boys.

PMID- 17536479
TI  - Empowerment or disempowerment? A review of youth training schemes for non-engaged
      young people in Hong Kong.
AB  - This paper investigates the school-to-work experiences of non-engaged youth aged
      15-24 who do not participate in education, training, and employment. Based on
      data from focus groups involving 50 non-engaged young people in Hong Kong, it
      examines how they are being systematically propelled to the edges of conventional
      pathways to adulthood, and assesses the efficacy of governmental training schemes
      that aim to develop employability as a strategy for engaging this population. The
      paper concludes by outlining prospects for future policy development, focusing on
      gaps and weaknesses in current provision and practice. It is suggested that
      effective guidance for non-engaged young people must pay attention to the social
      context of the individual. Assumptions behind the government's individualistic
      lifelong learning policy are called into question.

PMID- 17536480
TI  - Effective group work with delinquents in Hong Kong.
AB  - The principle of matching services to needs suggests that group work would be
      most effective when it targets those most in need of the services--delinquents
      with low involvement with the family and high involvement with friends. Less time
      with the family indicates a greater need for conventional social control, while
      more time with friends may entail a greater need for learning social skills in
      order to resist delinquent peer influences. To address these needs, developmental
      group work is appropriate for delinquents identified by social workers. The
      effectiveness of services tend to be contingent upon the delinquents'
      relationship with family and friends. To test this hypothesis, the present study
      collected data from 190 delinquents in Hong Kong. It was found that developmental
      group activities were beneficial to delinquents who spent less time with family
      and/or more time with friends. For delinquents in general, developmental group
      activities were helpful in diminishing delinquency. Moreover, the help was
      significantly greater for delinquents who spent more time with friends.

PMID- 17536481
TI  - Relations among weight control behaviors and eating attitudes, social physique
      anxiety, and fruit and vegetable consumption in Turkish adolescents.
AB  - This study examined the relationship among dieting, eating attitudes, social
      physique anxiety, and fruit and vegetable consumption among Turkish adolescents.
      Abnormal eating behavior (EAT-26 > or =20) was found in 32.8% of the total
      sample; this included 26.4% of the males and 38.7% of the females. Weight-control
      and weight-related behaviors are associated with high fruit and vegetable
      consumption in adolescents. Dieting was significantly associated with types of
      consumption in female adolescents. In addition, EAT-26 scores were significantly
      positively correlated with high fruit and vegetable consumption, but this
      association was not observed in SPAS scores among adolescents. Adolescents who
      engage in dieting behaviors seem to consume more fruit and vegetables than do
      other adolescents. Female adolescents may be more likely to display abnormal
      eating attitudes and dieting behaviors than do males. Although some weight
      control behaviors may be risky, adolescents who were practicing dieting behaviors
      engaged in the positive dietary behavior of consuming more servings of fruit and
      vegetables than did non-dieters.

PMID- 17536482
TI  - The motivations of adolescents who are addicted to online games: a cognitive
      perspective.
AB  - This research explored, from the perspective of cognitive theory, the
      psychological motivations of Taiwanese adolescents who are addicted to online
      games. Study 1 focused on the differential motivations between the addicts and
      nonaddicts. The findings revealed that the addicts exhibited higher intrinsic
      than extrinsic motivation, whereas the nonaddicts showed an opposite
      relationship. The intrinsic motivation of the addicts was also higher than the
      nonaddicts. The results imply that intrinsic motivation plays a crucial role in
      gaming addiction. Study 2 was conducted to examine whether four factors that
      moderate the detrimental effect of extrinsic motivators on intrinsic motivation
      would function as predicted. Results indicated that extrinsic rewards would
      undermine intrinsic motivation when they were high expectancy, high relevance,
      tangible, and noncontingent. Thus, players' intrinsic motivation would be higher
      when extrinsic rewards were low expectancy, low relevance, intangible, and
      contingent. This article provides insights into the differential motivations of
      the addicted players and how to employ intrinsic motivators to affect their
      intrinsic motivation.

PMID- 17536483
TI  - An empirical study of experiential value and lifestyles and their effects on
      satisfaction in adolescents: an example using online gaming.
AB  - This study tests a consumer behavioral model on Taiwanese adolescents and young
      adults engaging in online gaming. The major focus is on how these consumers
      transfer the value of their experiences and lifestyles to satisfaction, which may
      assist in the further exploration of the specific consumption behavior
      characteristics of adolescents and young adults, particularly with regard to
      their social functioning and deep-seated psychological needs. Using a two-stage
      sampling design process, data were collected on a total of 211 consumers, with
      the statistical analysis methods adopted for this study including a reliability
      test, confirmatory factor analysis, and LISREL analysis. Our results indicate
      that causal relationships hold in certain experiential value and lifestyle
      constructs. In particular, two experiential value constructs (social function,
      empathy and escapism) and two lifestyle constructs (pursuit of recreation and
      taste for life, reference group) play major roles that affect satisfaction among
      adolescents and young adults in online gaming in Taiwan.

PMID- 17536484
TI  - Molecular components of vertebrate Mg2+-homeostasis regulation.
AB  - Over the past decades, the clinical relevance and biological significance of Mg2+
      have been thoroughly documented. Although multiple Mg2+-transport pathways have
      been biophysically characterized, the molecular identity of the postulated
      components of Mg2+-homeostasis regulation in vertebrates remain undefined. Recent
      advances in the fields of genetics, genomics and proteomics, and novel
      technologies such as cDNA microarrays have allowed for substantial progress in
      this area. The mitochondrial Mrs2 protein was the first human Mg2+ transporter
      characterized as such, and an important element for future analyses of the role
      of mitochondria in managing intracellular Mg2+. Several molecules with Mg2+
      transport capabilities have been identified through a screen designed to find
      genes upregulated under hypomagnesic conditions. This includes SLC41A1 and 2,
      ACDP2 and MagT1. Finally, the elucidation of the molecular cause underlying two
      different hereditary diseases leading to hypomagnesemia resulted in the cloning
      and characterization of claudin 16 (paracellin-1), and TRPM6. Whereas claudin 16
      plays a crucial role in paracellular Mg2+ transport, TRPM6 is involved in the
      transcellular pathway. TRPM6 and its closest relative TRPM7 are both puzzling ion
      channel-kinase fusions, and perhaps the most unexpected newly identified players
      in the regulation of Mg2+-homeostasis in vertebrates.

PMID- 17536485
TI  - Moderate magnesium deprivation results in calcium retention and altered potassium
      and phosphorus excretion by postmenopausal women.
AB  - Enzyme and or hormone actions have not been shown to be consistently changed by
      consuming a low-magnesium diet similar to one that may occur in the general
      population. Thus, a human metabolic study was performed to determine whether
      deficient intakes of magnesium similar to those that occur naturally have
      pathophysiological effects through altering calcium retention and the metabolism
      of other minerals (sodium, potassium, phosphorus) involved in cellular ionic
      balance. Fifteen postmenopausal Caucasian women were recruited by advertisement
      throughout the United States. Eleven women (ages 49 to 71 years) completed the
      study as designed. The women resided in a metabolic research unit and consumed a
      basal Western-type diet that resulted in a mean intake of 4.40 mmol (107 mg)
      magnesium/d. The women were fed the basal diet supplemented with 9.05 mmol (220
      mg) magnesium/d for 18 d (equilibration) before being assigned to one of two
      groups in an experiment with a double blind, crossover design. One group was fed
      the basal diet and supplemented with a lactose placebo while the other group
      continued consuming the basal diet supplemented with 9.05 mmol magnesium/d for 72
      d, then each group switched to the other's diet, which they consumed for 72 d.
      Magnesium was supplemented as magnesium gluconate. Magnesium deprivation resulted
      in a non-positive magnesium balance (-0.21 mmol or -5 mg/d) that was highly
      positive during magnesium supplementation (+2.22 mmol or +54 mg/d). Magnesium
      deprivation decreased red blood cell membrane magnesium (2.5 versus 2.7 nmol or
      0.061 versus 0.065 microg/mg protein; p < or = 0.05). Magnesium deprivation
      increased calcium balance (+0.82 mmol or +35 mg/d versus -0.02 or -1 mg/d; p < or
      = 0.009); decreased the fecal excretion of phosphorus (28.9% versus 32.3% of
      intake; p < or =0.0001); increased the urinary excretion of phosphorus (73.4%
      versus 71.0%; p < 0.003); and decreased the urinary excretion of potassium (40.4
      mmol or 1.58 g/d versus 41.9 mmol or 1.64 g/d; p < 0.04). Non-positive magnesium
      balance and decreased red blood cell membrane magnesium concentration apparently
      are indicators of magnesium deprivation. Moderate magnesium deprivation achieved
      through diet alone results in increased calcium retention. Magnesium deprivation
      also alters phosphorus and potassium excretion. The changes indicate that an
      intake of 4.40 mmol (107 mg) magnesium/d is inadequate for postmenopausal women
      because of changes in cellular ionic balance that may lead to pathophysiological
      conditions.

PMID- 17536486
TI  - Magnesium intake and serum C-reactive protein levels in children.
AB  - The objective of this study was to determine whether magnesium consumption is
      associated with inflammation (C-reactive protein [CRP]) in children. The study
      was an analysis of child (age 6-17 years) participants in the cross-sectional,
      nationally representative National Health and Nutrition Examination Survey
      (NHANES). Children consuming less than 75% of RDA were 1.94 times more likely (p
      < 0.05) to have elevated serum CRP levels than children consuming above the RDA.
      In adjusted analyses controlling for demographics, cardiovascular risk factors,
      and BMI, children with consumption of less than 75% RDA were 58% more likely to
      have elevated CRP (OR 1.58, 95% CI 1.07-infinity). Children with intakes below
      the RDA are more likely to have elevated CRP levels.

PMID- 17536487
TI  - The effect of intravenous magnesium sulfate infusion on serum levels of sodium
      and potassium in patients with aneurysmal subarachnoid hemorrhage.
AB  - Abnormal serum sodium levels are frequently observed among patients with
      aneurysmal subarachnoid hemorrhage (SAH) and may worsen cerebral edema or mass
      effect. Low serum potassium levels (hypokalemia) are also common among patients
      with aneurysmal SAH and are associated with prolonged QT interval and ventricular
      arrhythmia. Recent meta-analysis suggests that MgSO4 infusion improves the
      clinical outcome in patients after aneurysmal SAH; however, MgSO4 infusion may
      theoretically exacerbate electrolyte disturbance. We retrospectively reviewed the
      prospectively collected demographic and laboratory data of 100 patients after
      aneurysmal subarachnoid SAH in a neurosurgical center in Hong Kong. 51 patients
      had daily magnesium sulfate infusion for 14 days (Group 1) and 49 patients were
      managed similarly, without magnesium sulfate infusion (Group 2). Days of
      hypernatremia (mean+/-SD) were 2.0+/-2.7 for group 1 and 2.0+/-2.5 for group 2, p
      = 0.999; days of hyponatremia (mean+/-SD) were 2.7+/-3.1 for group 1 and 2.0+/
      2.9 for group 2, p = 0.230; days of hypokalemia (mean+/-SD) were 4.5+/-3.1 for
      group 1 and 4.5+/-3.2 for group 2, p = 0.819. Hyperkalemia was uncommon in both
      groups. There was also no statistically significant difference between the two
      groups when the data were re-analyzed as severe hyponatremia, severe hypokalemia
      and severe hyperkalemia. Magnesium sulfate infusion was safe and did not seem to
      exacerbate the duration of electrolyte disturbance associated with aneurysmal
      subarachnoid hemorrhage.

PMID- 17536488
TI  - Contents of bioelements and toxic metals in the Polish population determined by
      hair analysis. Part III. Adults aged 20 to 40 years.
AB  - The aim of the present study was to define referential values of 5 basic
      bioelements (Ca, Mg, Zn, Cu, Fe) and 2 toxic metals (Pb and Cd) in the hair of
      Polish adults aged 20 to 40 years, based on the research conducted from 1991 to
      2006 on a group of 5733 formally healthy subjects of both sexes. The results of
      our biochemical tests were subjected to statistical analysis and they can be
      treated as referential norms for the concentrations of analyzed bioelements in
      the hair of the Polish population. Our analyses confirm significant differences
      in accumulations of certain elements in women's and men's hair. We established
      that women's hair Ca, Mg, Zn (p = 0.000000) and hair Cu (p = 0.0001)
      concentrations are higher than they are in men. A lower mean of hair Fe
      concentrations in women were confirmed by some tests. Men have significantly
      higher (p = 0.0000) concentrations of toxic metals (hair Pb and Cd), which keep
      increasing with age. Analyses of correlations confirm significance (for the
      assumed level of significance alpha = 0.05) of synergistic interactions between
      bioelements: Ca-Mg (r = +0.70), Ca-Zn (r = +0.39), Ca-Cu (r = +0.14), Mg-Zn (r =
      +0.31), Mg-Cu (r = +0.10), Zn-Cu (r = +0.11), Zn-Fe (r = +0.07). Significance (a
      < 0.05) of antagonistic interactions with toxic metals: Ca-Pb (r = -0.13), Zn-Pb
      (r = -0.15), Mg-Pb (r = -0.15), Zn-Cd (r =-0.02) was confirmed. Significance
      (alpha < 0.05) of synergistic effects with toxic metals: Pb-Cd (r = +0.35), Fe-Pb
      (r = +0.16), Fe-Cd (r = +0.08) was also confirmed. Adults in whose hair
      bioelements and hair toxic metals concentrations have shown values outlying from
      reference and who have too many toxic elements and too few bioelements should
      undergo further diagnostic tests since the results could be a sign of
      disturbances that could lead to various diseases.

PMID- 17536489
TI  - Serum magnesium concentration in drug-addicted patients.
AB  - Drug addiction is a complex problem which leads to many somatic, psychic and
      social diseases. It is accompanied by the disturbed metabolism of various macro
      and micronutrients. The aim of this study was to assess serum magnesium
      concentration in drug-addicted patients and analyze whether Human
      Immunodeficiency Virus (HIV) infection and methadone treatment affect the level
      of serum magnesium in these patients. The examination was conducted in a group of
      83 people - patients of Szczecin-Zdroje Psychiatric Hospital (Poland). They were
      21 to 49 years old, and the mean age was 32 +/- 7 years. The control group
      consisted of 81 healthy individuals. Flame atomic-absorption spectrometry method
      was used to determine the magnesium concentration. The total serum magnesium
      concentration was calculated for the whole patient group, subgroups of women and
      men, a subgroup of people infected with HIV, and a subgroup receiving methadone
      substitution treatment. How magnesium behaves depending on age and addiction
      period, was checked. The mean concentration of magnesium in blood serum of the
      patients examined was 0.57 mmol/L, which was significantly lower than in the
      control group. In the subgroup of men it was 0.57 mmol/L, and in the subgroup of
      women - 0.55 mmol/L; the differences were not statistically significant. In the
      patient group nobody had the appropriate magnesium concentration in blood serum.
      No significant correlation was found between the magnesium concentration, age of
      the patients and addiction period. In the subgroup of seropositive people the
      mean concentration of magnesium was 0.55 mmol/L, and in the subgroup of non
      infected patients - 0.58 mmol/L; the difference was not statistically
      significant. The mean concentration of magnesium in the subgroup treated with
      methadone was 0.59 mmol/L, and in the subgroup not involved in this type of
      therapy - 0.55 mmol/L; it was not a statistically significant difference.

PMID- 17536490
TI  - Magnesium deficiency reduces fear-induced conditional lick suppression in mice.
AB  - The consequences of broad-scale alterations in magnesium (Mg2+) levels on
      learning and memory are poorly understood. We have recently demonstrated that
      adult male mice maintained on an Mg2+-deficient diet exhibit reduced conditional
      freezing behavior. The purpose of the present study was to determine if the
      detrimental effect of Mg2+ deficiency in mice extended to another measure of
      conditional fear, conditioned lick suppression (CLS), as well as to another form
      of learning, spatial learning in the swim maze task. Adult male C57Bl/6J mice
      were provided with a normal or Mg2+-deficient diet and were trained and tested
      ten days later for conditional fear, using CLS and freezing as indicators of
      learning. Learning in the swim maze was tested in a separate cohort of mice
      during days 14-18 of diet exposure. Mg2+-deficient mice showed reduced CLS as
      well as conditional freezing behavior in comparison to control mice. However,
      learning in the swim maze task was normal in Mg2+-deficient mice. These studies
      indicate that the detrimental effects of Mg2+ deficiency extend to other measures
      of conditional fear but not to all forms of learning.

PMID- 17536491
TI  - Low-magnesium induces senescent features in cultured human endothelial cells.
AB  - Low magnesium (Mg) affects endothelial function, thus playing a role in
      cardiovascular diseases, including atherosclerosis. We here show that Mg
      deficiency acts through the induction of the pro-inflammatory cytokine
      interleukin (IL)-lalpha in cultured human endothelial cells. Indeed, the
      inhibition of IL-lalpha prevents low Mg-induced adhesion of monocytoid cells to
      the endothelium as well as the upregulation of the cdk inhibitor p21. We also
      demonstrate that Mg deficiency induces several features typically associated with
      endothelial senescence. While low Mg can affect gene expression at the
      transcriptional level, it also modulates the activity of the proteasome. Since
      endothelial senescence contributes to atherogenesis, our findings indicating that
      low Mg promotes senescence may shed some light on the molecular mechanisms
      linking Mg deficiency to cardiovascular diseases.

PMID- 17536492
TI  - Comparison between measured and calculated ionised concentrations in Mg2+ /ATP,
      Mg2+ /EDTA and Ca2+ /EGTA buffers; influence of changes in temperature, pH and
      pipetting errors on the ionised concentrations.
AB  - The apparent dissociation constants (Kapp) and total ligand concentrations
      ([Ligand]T) from extensive published and unpublished macroelectrode measurements
      for Mg2+/ATP, Mg2+/EDTA and Ca2+/EGTA buffers have been recalculated. These
      calculations were made feasible by the introduction of an Excel program which
      reduced the time of calculation for Kapp and [Ligand]T from over an hour to under
      five minutes. These estimations of Kapp and [Ligand]T allowed, not only a
      comparison between measured and calculated ionised magnesium and calcium
      concentrations ([Mg2+] and [Ca2+]) for Mg2+/ATP, Mg2+/EDTA and Ca2+/EGTA buffers
      but also a comparison amongst calculated values. Calculated [X2]1 values always
      differed from measured, and calculated values differed amongst themselves by
      factors of at least 2. These variations cast doubts on the published absolute
      values for intracellular [Mg2+] estimated by 31P-NMR and the resting values for
      [Ca2+] in cells. The allowable range for [X2+] in the buffers and consequently
      for Kapp and [Ligand]T has not been defined, which introduces uncertainties into
      published absolute values for [X2+]. This paper shows that an upper limit of +/-
      10% deviation from the mean value for [X2+] is attainable. This requires the
      temperature to be maintained within +/- 0.5 degrees C, pH within +/- 0.01 units
      and pipetting errors of less than 0.25%. Until internationally defined buffer
      standards are available, the lack of correlation between measured and calculated
      [X2+] means that measurement of Kapp and [Ligand]T and hence [X2+] is more
      reliable than calculation.

PMID- 17536493
TI  - Which statin, what dose?
AB  - Five prescribable statins are licensed in the UK: atorvastatin (Lipitor);
      fluvastatin (Lescol); pravastatin (Lipostat or generic); rosuvastatin (Crestor);
      simvastatin (Zocor or generic or branded generic e.g. Simvador). Here we discuss
      the relative merits of different statins in addressing cardiovascular risk.

PMID- 17536494
TI  - Update on drugs for hyperactivity in childhood.
AB  - In 2001, we concluded that methylphenidate or dexamfetamine can be useful
      adjunctive therapy for children with severe hyperactivity in whom non-drug
      approaches alone have been inadequate. Since then, atomoxetine (pronounced a-toe
      moks-e-teen; Strattera - Lilly) and three modified-release formulations of
      methylphenidate have been launched for attention deficit hyperactivity disorder
      (ADHD). Here we reconsider drugs for ADHD in childhood, focusing on the newer
      products.

PMID- 17536495
TI  - [Current topics in diabetic retinopathy].

PMID- 17536496
TI  - [Study of surgical procedures for retinal detachment with macular hole].
AB  - PURPOSE: To evaluate the surgical outcome of retinal reattachment, the
      reattachment rate according to the range of detachment, and postoperative visual
      acuity for macular hole retinal detachment (MHRD). SUBJECTS AND METHODS: Sixty
      eight eyes of 67 patients with MHRD were analyzed. The mean follow-up period was
      54 months. RESULTS: Retinal reattachment occurred in 42/68 eyes (62%) after
      initial surgery. The reattachment rates were 6/23 eyes (26%) in the gas tamponade
      group, 13/19 eyes (68%) in the vitrectomy group, 23/ 26 eyes (88%) in the group
      that underwent removal of internal limiting membrane as adjunct to vitrectomy
      (ILM) group. In the additional surgery, the reattachment rates were 5/9 eyes
      (56%) in the gas tamponade group, 13 eyes (100%) in the vitrectomy group, 1/2
      eyes (50%) in the ILM group, and 6 eyes (100%) in the macular prombe buckling
      group. No significant differences were seen in the detachment extent-related
      reattachment rate within the same surgery and the postoperative visual acuity
      between the groups. CONCLUSION: The results show that removal of ILM contributes
      to successful reattachment in the initial surgery, and that for non-reattachable
      eyes, macular buckling in the second surgery is the most reliable method.

PMID- 17536497
TI  - [Evaluation of disinfectant against adenovirus by real-time polymerase chain
      reaction].
AB  - PURPOSE: To evaluate the effect of disinfectant against human adenovirus (HAdV)
      using a real-time polymerase chain reaction method. METHODS: Ethanol, povidone
      iodine, and sodium hypochlorite were mixed with HAdV-3, -4, -8, -19, and -37. A
      diluted mixed solution was infected with A549 cells for six days and then the
      number of HAdV DNA copies was counted. A reduction in the number of HAdV DNA
      copyies by 4 log was considered as virucidal activity. RESULTS: Ethanol at 80%
      concentration was effective against all serotypes after ten minutes, but 70% and
      40% concentrations of ethanol were ineffective against all serotypes. Povidone
      iodine at 0.2% concentration was effective against HAdV-3, -4, -19, and -37 after
      one minute, and against HAdV-8 after three minutes. Sodium hypochlorite (0.1%
      concentration) was effective against all serotypes after 15 seconds. CONCLUSION:
      While all disinfectants were effective against HAdV, the effective concentration
      percentages and the times required were different, which indicates the importance
      of deliberating on the concentration, application time and location to apply the
      disinfectant, and what equipment to use for application.

PMID- 17536498
TI  - [Deep lamellar keratoplasty in severe ocular surface disease].
AB  - PURPOSE: To demonstrate the efficacy and safety of deep lamellar
      keratoplasty(DLKP) in the treatment of corneal opacity in severe ocular surface
      disease. METHODS: A total of 12 eyes of 11 patients were analyzed in this
      retrospective case series. The original diseases were Stevens Johnson syndrome
      (SJS : 3 eyes), ocular ciccatricial pemphigoid(OCP : 2 eyes), thermal burns (2
      eyes), limbal deficiency due to unknown cause (2 eyes), and corneal scarring due
      to trachoma (3 eyes). Cases with total limbal deficiency (6 eyes) were also
      treated with secondary or simultaneous limbal transplantation. Cataract surgery
      was also performed in 4 eyes following DLKP. RESULTS: DLKP was successfully done
      in all cases. One case with SJS experienced an immunological rejection against
      the limbal graft. Two eyes with SJS eventually developed ulcers that required
      therapeutic penefrating keratoplasty. Visual improvement was observed in 9 out of
      12 eyes, of which 2 cases maintained a corrected visual acuity of 0.1 despite
      conjunctivalization of the ocular surface. CONCLUSION: DLKP is an effective means
      to treat stromal opacity in patients with ocular surface disease.

PMID- 17536499
TI  - [Relationship between retinopathy development and systemic factors in type 2
      childhood diabetes].
AB  - PURPOSE: To clarify the relationship between systemic factors and the development
      of retinopathy in patients with type 2 childhood diabetes. SUBJECTS AND METHODS:
      We evaluated the relationship between retinopathy incidence and systemic factors
      (i.e., sex, age at diagnosis, and mean HbA(1c)) in 36 patients (11 boys and 25
      girls). RESULTS: Ten of the 36 cases (28%) developed retinopathy during a mean
      observation period of 7 years and 11 months. Retinopathy was found only in female
      patients. The mean HbA(1c) value correlated significantly with the onset of
      retinopathy. The incidence of retinopathy in the patients with mean HbA(1c)
      values less than 8.0% was 0% at 5 and 10 years, and 5% at 15 years. On the other
      hand, the incidence of retinopathy in the patients with mean HbA(1c) values of
      8.0% or more was 44% at 5 years, and 56% at 10 and 15 years after the diagnosis
      of diabetes. CONCLUSION: As female patients with mean HbA(1c) values of 8.0% or
      more have a high risk of developing retinopathy, strict blood glucose control and
      frequent ophthalmologic examinations are necessary.

PMID- 17536500
TI  - [Long-term results of grid pattern photocoagulation for diffuse diabetic macular
      edema].
AB  - PURPOSE: To investigate the long-term results of grid pattern photocoagulation
      for diffuse diabetic macular edema. SUBJECTS AND METHODS: In 45 cases, 56 eyes
      foveal thickness and visual outcome were observed 12 months or more after grid
      pattern photocoagulation. RESULTS: Compared with preoperative values, average
      foveal thickness decreased significantly during the initial 3 postoperative
      months and this reduction was maintained through 30 postoperative months. Foveal
      thickness was reduced by more than 20% in 66% of eyes. The final logarithm of the
      minimum angle of resolution (logMAR) visual acuity improved 0.2 or more in 41% of
      eyes. There was a significant correlation between preoperative and postoperative
      visual acuity. A final visual acuity of 0.5 or better was obtained in 80% of eyes
      with a preoperative visual acuity of 0.4 or better. There were no eyes with
      visual loss due to atrophic creep in this study. CONCLUSION: Grid pattern
      photocoagulation for diffuse diabetic macular edema showed long-term
      effectiveness in reducing foveal thickness postoperatively. It will be possible
      to achieve a final visual acuity of 0.5 or better in a high percentage of cases,
      if grid pattern photocoagulation is performed for those with relatively good
      visual acuity. The foveal thickness measurement was useful for quantitative
      evaluation of photocoagulation for diabetic macular edema.

PMID- 17536501
TI  - [Visual course for proliferative diabetic retinopathy after pars plana
      vitrectomy].
AB  - PURPOSE: To investigate retrospectively the visual course for proliferative
      diabetic retinopathy after pars plana vitrectomy. CASES AND METHODS: From January
      2002 to December 2004, we operated 209 eyes with proliferative diabetic
      retinopathy. For this study, we selected 28 eyes in which the visual acuity could
      be followed for 6 months or longer after the vitrectomy. RESULT: The mean time
      period for reaching the best visual acuity after vitrectomy was 14.7 +/- 12.0
      months. Depending on the type of diabetic maculopathy, the ischemic type, deposit
      type, and cystoid macular edema type required a mean time of 16 approximately 19
      months. For the diffuse edema type, the mean was 9 months. It is significant that
      vitrectomy with triamcinolone acetonide (TA) resulted in visual improvement
      earlier than vitrectmy without TA (p value = 0.03).

PMID- 17536502
TI  - [Notes on ophthalmological terms. 14. Article citation: 2) Bibliography of
      Takayasu disease and the frequency of citation of the original articles].

PMID- 17536503
TI  - [Ionotropic glutamate receptor trafficking--there and back again].
AB  - Glutamate is a major excitatory neurotransmitter in brain. It engages mainly
      ionotropic glutamate receptors of AMPA and NMDA type. Thus, regulation of the
      number and properties of the receptors is crucial for correct neuronal
      communication, but also contributes to various forms of synaptic plasticity,
      namely neuronal development, learning and memory. Glutamate receptors are not
      static components of synapses. On the contrary, they are continuously delivered
      and removed from postsynaptic membranes and this process is regulated by synaptic
      activity, Receptor trafficking to synapses is a multi-step process, involving
      exit from endoplasmic reticulum, transport along dendrites, incorporation to
      postsynaptic membrane and finally removing them from synapses. The transport is
      regulated by numerous proteins, especially those bearing PDZ domains, or by
      receptors themselves.

PMID- 17536504
TI  - [Signaling pathways of transforming growth factor beta family members].
AB  - Transforming growth factor beta (TGF-beta) signaling controls varies of cellular
      processes, including cell proliferation, differentiation, fibrosis, apoptosis and
      specification of developmental fate during embryogenesis as well as in mature
      tissues. The members of TGF-betas family are secreted as inactive (latent)
      precursors, what prevents uncontrolled activation of the cognate receptors. After
      activation TGF-beta ligand initiates signaling by binding to and bringing
      together type I and type II receptor serine/threronine kinases on the cell
      surface. Recent cellular, biochemical and structural studies have revealed
      significant insight into the mechanisms of the activation of TGF-beta receptors
      through ligand binding, the activation of Smad proteins through phosphorylation
      as well as Smad independent pathways.

PMID- 17536505
TI  - [Growth hormone signaling pathways].
AB  - The substantial improvement in the studies on a very complicated mechanism--
      growth hormone signaling in a cell, has been noted in last decade. GH-induced
      signaling is characterized by activation of several pathways, including
      extracellular signal-regulated kinase (ERK), the signal transducer and activator
      of transcription and phosphatidylinositol-3 kinase (PI3) pathways. This review
      shows a current model of the growth hormone receptor dimerization, rotation of
      subunits and JAK2 kinase activation as the initial steps in the cascade of
      events. In the next stages of the signaling process, the GH-(GHR)2-(JAK2)2
      complex may activate signaling molecules such as Stat, IRS-1 and IRS-2, and
      particularly all cascade proteins that activate MAP kinase. These pathways
      regulate basal cellular functions including target gene transcription, enzymatic
      activity and metabolite transport. Therefore growth hormone is considered as a
      major regulator of postnatal growth and metabolism, probably for mammary gland
      growth and development too.

PMID- 17536506
TI  - [The role of ion channels in apoptosis].
AB  - The plasma membrane as well as the mitochondrial outer and inner membranes
      contain a number of ion channels that are responsible not only for existence of
      cells under physiological conditions but they also participate directly in
      apoptosis. In the apoptotic cells the activated K+, Cl- channels of plasma
      membrane control the cell volume and mediate the regulation of protease and
      nuclease activities. The mitochondrial channels are involved in the ionic
      movements and leakage of apoptogenic factors from the intermembrane space to
      cytosol. During apoptosis, an important role in the permeabilization of the outer
      mitochondrial membrane play Bcl-2 family proteins. In this review the recent
      findings on the function of ion channels in apoptotic cells and the role played
      by Bcl-2 proteins in the control of apoptosis are discussed.

PMID- 17536507
TI  - [Phosphorylation of serine-arginine rich proteins--pleiotropic effect of one type
      posttranslational modification].
AB  - SR proteins are components of the spliceosome, a dynamic complex catalysing
      removal of pre-mRNA introns during splicing reaction. Recent studies have shown
      additional functions for SR proteins in mRNA transport and translation. Several
      protein kinases have been identified that can phosphorylate SR proteins.
      Phosphorylation is a common posttranslational modification among proteins.
      However in the case of SR proteins it has got a special meaning. Phosphorylation
      of serine residues clustered in a narrow area of RS domains affects all aspects
      of SR proteins functions. It influences subcellular localization and determines
      process in which the proteins take part.

PMID- 17536508
TI  - [Nonsense-mediated mRNA decay (NMD)--on guard of mRNA quality].
AB  - Nonsense-mediated mRNA decay (NMD) is a surveillance pathway that protects cells
      from potentially harmful effects of truncated proteins that would otherwise be
      translated from mRNAs bearing premature termination codons (PTC). NMD targets not
      only aberrant mRNAs possessing PTCs resulting from mutations, transcription
      errors or abnormal splicing but is also thought to be involved in regulating the
      expression of several wild-type transcripts (approximately 10% of the
      transcriptome). NMD is a conserved pathway present in all eukaryotic organisms
      studied so far (yeast, nematoda, flies, mammals and plants). The key players
      involved in NMD are also conserved among these species. However, details of NMD
      mechanism vary among eukaryotic organisms studied so far.

PMID- 17536509
TI  - [Hepatitis C virus--structure, replication and therapeutical opportunities and
      the phenomenon of resistance].
AB  - Genetic material of HCV consists of single-strained RNA. Generation of HCV
      mutants insensitive to the immune system activity and resistant to used
      medications seem to be a consequence of HCV genetic variability, unusual
      replication potential and selection pressure of the host organism. During only
      one day 10(12) of viral particles may be formed, many of which contain mutations.
      Selection pressure put by the immune system and used medications lead to the
      selection of new HCV variants insensitive to therapeutics. The aim of the study
      is to draw attention (by means of discussing the structure and replication of
      HCV) to therapeutical problems of chronic hepatitis C consisting of the biology
      of the virus. Clinical and laboratory factors dependent on the patient (e.g.
      biochemical, histopathological, genotype) were omitted.

PMID- 17536510
TI  - [Molecular methods for diagnostics and assessment of treatment effectiveness in
      modern pediatric hematooncology].
AB  - This paper is a review of current diagnostic applications of molecular methods in
      pediatric hematooncology, including analyses performed at disease presentation,
      evaluation of prognosis as well as those for assessment of treatment
      effectiveness. Here we present the examples of important fields of application of
      molecular methods in pediatric hematooncology, i.e. identification of clinically
      significant fusion genes in acute lymphoblastic leukemia and monitoring of
      minimal residual disease in this most frequent childhood malignancy. Moreover, we
      present the methodology and clinical significance of quantitative analysis of
      hematopoietic chimerism after allogeneic stem cell transplantation. The methods
      presented include fluorescent in situ hybridization, reverse transcription,
      conventional and quantitative polymerase chain reaction, as well as methods of
      genotyping based on analysis of microsatellite marker polymorphism, single
      nucleotide polymorphism, and Indel markers.

PMID- 17536511
TI  - [The role of homocysteine thiolactone in some of human diseases].
AB  - In the present article we discuss the most recent data regarding the role of
      homocysteine, its cyclic thioester--homocysteine thiolactone and the process of
      protein N-homocysteinylation in human disease. The protective role of
      thiolactonase/paraoxonase enzyme, carried on high density lipoproteins (HDL) in
      human blood, as well as the influence of structural modifications on HDL function
      are discussed. We also describe the effect of vitamin therapy (folic acid,
      vitamins: B6, B12) used for lowering the homocysteine level in humans as well.

PMID- 17536512
TI  - [Immunoproteomics of Helicobacter pylori--strategy for improvement of diagnostic
      tests and vaccine development].
AB  - Helicobacter pylori, Gram-negative spiral-shaped bacteria, member of epsilon
      Proteobacteria, colonizes the gastric mucosa of humans. H. pylori has been
      identified as the causative agent of chronic inflammation, chronic gastritis and
      peptic ulceration and is considered a risk factor for the development of mucosa
      associated lymphoid tissue lymphoma and adenocarcinoma of the stomach. Although
      more than 50% of human population is infected with H. pylori only a subset
      develops disease. The completion of two H. pylori genome sequences revealed the
      enormous strain heterogeneity and permitted comparative proteome analysis.
      Immunoproteomics, a novel strategy combining standard proteomics with
      immunological screening, is currently method of choice for identification of new
      antigens of diagnostic and protective values. Highly specific antigens will be
      used as biomarkers of different pathology induced by H. pylori infection whereas
      novel highly immunogenic, conserved, abundant and surface-located proteins will
      facilitate efficient anti-Helicobacter vaccine construction.

PMID- 17536513
TI  - [Decade of genomics--methods for genome investigation in yeast Saccharomyces
      cerevisiae].
AB  - The last ten years, since yeast Saccharomyces cerevisiae genome was sequenced,
      brought a big impact in genome-wide techniques. The tenth anniversary of genomic
      era provokes the following resume: a lot of new methods were invented. The yeast
      strains libraries carrying transposon insertions, gene deletions or tagged
      proteins have been created. Using them, the phenotypes of gene deletions, as well
      as the biological activity, cellular localization and possible modifications of
      their protein products were elucidated. SAGE analysis and DNA microarray
      experiments showed gene expression profiles and allowed to build interaction
      networks of gene regulation. The two dimensional gels, mass spectrometry, protein
      arrays and two-hybrid system carry information about protein interactions,
      modifications, and biochemical activities. All these methods permit to increase
      the number of genes with known cellular functions. Moreover, testing these
      techniques on yeast S. cerevisiae--a model eukaryotic organism--opened the door
      for their usage in all other species.

PMID- 17536516
TI  - Arthroscopic tennis elbow release.
AB  - Tennis elbow is a common affliction manifested by symptoms of lateral elbow pain
      and diminished grip strength. Conservative treatment measures will lead to
      symptom resolution in most cases. Surgery is reserved for patients with
      recalcitrant elbow pain unresponsive to nonsurgical management. This article
      reviews the technique of arthroscopic tennis elbow release surgery, including
      indications, contraindications, complications, postoperative rehabilitation, and
      outcome.

PMID- 17536514
TI  - [Recombinant protein production in Escherichia coli].
AB  - Growing needs for efficient recombinant production pose new challenges; starting
      from cell growth optimization under overexpression conditions, improving vectors,
      gene and protein sequence to suit them to protein biosynthesis machinery of the
      host, through extending the knowledge of protein folding, fusion protein
      construction, and coexpression systems, to improvements in protein purification
      and renaturation technologies. Hitherto Escherichia coli is the most defined and
      the cheapest protein biosynthesis system. With its wealth of available mutants
      tested is the best suited to economically test new gene constructs and to scale
      up the recombinant protein production.

PMID- 17536517
TI  - External rotation humeral osteotomy for brachial plexus birth palsy.
AB  - In patients with brachial plexus birth palsy, persistent muscular imbalance
      across the developing shoulder results in progressive glenohumeral dysplasia,
      characterized by increased glenoid retroversion, humeral head flattening, and
      posterior subluxation of the humeral head. Soft-tissue procedures-such as tendon
      transfers and musculotendinous lengthenings--will provide limited functional
      improvements in the setting of advanced glenohumeral deformity. For patients with
      internal rotation contracture and external rotation weakness associated with
      severe glenohumeral dysplasia, external rotation osteotomy of the humerus may be
      used to improve global shoulder function. The purpose of this article is to
      review the history, indications, and surgical technique of external rotation
      humeral osteotomy for patients with brachial plexus birth palsy.

PMID- 17536518
TI  - Technique of the double nerve transfer to recover elbow flexion in C5, C6, or C5
      to C7 brachial plexus palsy.
AB  - In C5, C6, or C5-to-C7 root injuries, many surgical procedures have been proposed
      to restore active elbow flexion. Nerve grafts or nerve transfers are the main
      techniques being carried out. The transfer of ulnar nerve fascicles to the biceps
      branch of the musculocutaneous nerve is currently proposed to restore active
      elbow flexion. Recovery of biceps muscle function is generally sufficient to
      obtain elbow flexion. However, the strength of elbow flexion is sometimes weak
      because the brachialis muscle is not reinnervated. Therefore, the transfer of 1
      fascicle of the median nerve to the brachialis branch of the musculocutaneous
      nerve may be proposed to improve strength of the elbow flexion. We describe the
      technique of this double transfer to restore elbow flexion. The results
      concerning 5 patients are presented.

PMID- 17536519
TI  - Anterior elbow dislocation with potential compartment syndrome: a case report.
AB  - Anterior elbow dislocation is an infrequent lesion, usually produced by direct
      trauma to the proximal ulna after a fall on the elbow in flexion, and is often
      associated with soft tissue injuries. The authors report a case of a complex
      injury produced by a high-energy trauma in the right arm of a 65-year-old
      patient. His limb was trapped inside an industrial spin-dryer, resulting in a
      closed anterior elbow dislocation, diaphyseal ulnar shaft, radial styloid process
      fractures, and an associated compartment syndrome. The injury mechanism and its
      treatment are described to better manage the soft tissue injury and early elbow
      mobilization using the FEARM hinged external fixator. A good result was achieved,
      with almost complete restoration of the patient's arm functions, and he has
      returned to his previous working activities.

PMID- 17536520
TI  - Capitolunate arthrodesis with compression screws.
AB  - Scapholunate dissociation or scaphoid pseudarthrosis may lead to wrist
      osteoarthritis. When osteoarthritis concerns the midcarpal joint, proximal row
      carpectomy is not possible. Only 4-corner or capitolunate arthrodesis may be
      indicated. In this procedure, pseudarthrosis was frequently described in
      literature. However, in these series, fixation was performed with pins or
      staples. Type and position of the device are important to obtain carpal bones
      fusion. The efficiency of compression screws has been validated in scaphoid
      fracture or pseudarthrosis. Moreover, the axial position of the screws, parallel
      to the physiological wrist loads, may participate to improve bone fusion.
      Therefore, we present our technique of capitolunate arthrodesis with compression
      screws fixation through a dorsal approach.

PMID- 17536521
TI  - Wrist arthrodesis after double free-muscle transfer in traumatic total brachial
      plexus palsy.
AB  - Double free-muscle transfer is a technique used to treat patients with total
      brachial plexus palsy to restore hand prehension. It involves the reconstruction
      of shoulder stability, the transfer of 2 functioning gracilis muscles, and other
      complementary procedures to optimize the function of the transferred muscles.
      Wrist arthrodesis is one of these complementary procedures. Our technique of
      wrist arthrodesis in these patients is different from the standard technique. In
      this article, we describe our technique and experience of wrist arthrodesis in
      patients with complete brachial plexus palsy treated with double free-muscle
      transfer technique. In our procedure, the plate is fixed from the second
      metacarpal--and not the third as is the usual practice--to the radius to avoid
      friction with the extensor digitorum communis tendons. A very small bone graft,
      prepared from the removed Lister tubercle, is needed because of the very thin
      articular cartilage in these patients. A short arm splint is used for only 1 week
      postoperatively to avoid finger stiffness. There were no major complications such
      as pseudoarthrosis or metal failure in our patients because the affected limb is
      subjected only to mild stresses.

PMID- 17536522
TI  - The distal radioulnar joint: contemporary perspectives.

PMID- 17536523
TI  - Distal radioulnar joint arthroscopy and the volar ulnar portal.
AB  - Pain on the ulnar side of the wrist remains poorly understood. As attention has
      shifted toward the myriad causes of ulnar-sided wrist pain, the utility of
      viewing the wrist from a volar ulnar (VU) perspective has emerged. Lunotriquetral
      ligament tears have been implicated in the pathogenesis of volar intercalated
      segmental instabilities. They often originate in the palmar subregion, which is
      most important for maintaining stability. These tears are difficult to visualize
      through the 4, 5, or 6R portals. They are well seen through a VU portal, and the
      direct line of sight facilitates debridement. The VU portal has potential use in
      the arthroscopic diagnosis and treatment of patients with injuries to the ulnar
      sling mechanism. It aids in triangular fibrocartilage repairs especially those
      involving the dorsal aspect between the ulnar styloid and the radial insertion,
      because the proximity of the 4, 5, and 6R portals makes triangulation of the
      instruments difficult. Although arthroscopy of the dorsal aspect of the distal
      radioulnar joint has been well described, it has largely remained a curiosity,
      with few clinical indications. Recent biomechanical studies have highlighted the
      importance of the deep attachment of the triangular fibrocartilage complex in
      maintaining distal radioulnar joint stability. The volar distal radioulnar portal
      is useful for assessing the foveal attachment. It may be used where there is the
      suspicion of a peripheral triangular fibrocartilage detachment due to a loss of
      its normal tension despite the lack of a visible tear during radiocarpal
      arthroscopy. The judicious use of these portals deserves consideration for
      inclusion as part of a thorough arthroscopic examination of selected patients
      with ulnar-sided wrist pain.

PMID- 17536524
TI  - Suture welding for arthroscopic repair of peripheral triangular fibrocartilage
      complex tears.
AB  - This report presents a method of arthroscopic repair of the peripheral triangular
      fibrocartilage tears by using ultrasonic suture welding technique, thus avoiding
      the need for traditional suture knots. This technique eliminates the potential
      causes of ulnar-sided wrist discomfort especially during the postoperative
      period. Twenty-three patients (9 women and 14 men; mean age, 35 years; range, 18
      52 years) were operated during a 1-year period in 2001 for Palmer grade 1B
      triangular fibrocartilage complex tear and followed up for 17 months. At the
      final follow-up, the average wrist arc of motion was as follows: extension, 65
      degrees; flexion, 56 degrees; supination, 80 degrees; pronation, 78 degrees;
      radial deviation, 12 degrees; and ulnar deviation, 25 degrees. Grip strength
      measured with a dynamometer (Jamar) averaged 81% of the contralateral side at the
      final evaluation (range, 53%-105%).

PMID- 17536525
TI  - Surgical approaches to the distal radioulnar joint.
AB  - The distal radioulnar joint (DRUJ) is classified as a uniaxial synovial pivot
      joint between the convex head of the ulna and the concave ulnar notch of the
      radius. The DRUJ can be approached from 3 sides with a refined dorsal approach
      retaining a robust retinacular-dorsal capsular layer preferred by most surgeons.
      Recent descriptions of safe and extensile volar approaches have broadened
      indications for a volar approach to the DRUJ. A subcutaneous ulnar approach
      remains an option particularly when dealing with additional distal ulnar
      pathology. A description of technique and review of the surgical experience in
      exposure and treatment of DRUJ pathology will be presented, with advantages,
      disadvantages, and authors' preferred techniques.

PMID- 17536526
TI  - Technique of ulnar shortening.
AB  - Ulnar shortening or recession is a common treatment for an expanding number of
      clinical indications. This procedure has become more reliably performed because
      of specialized equipment that permits the creation of 2 precise 45-degree
      osteotomy surfaces and a known amount of ulnar shortening. Further refinements in
      technique have facilitated compression of the osteotomy surfaces and application
      of an interfragmentary lag screw at a specified angle. More recently,
      advancements in technology have increased the surgical options available to the
      surgeon and have provided for a low-profile surgical plate that may be placed on
      either the ulnar subcutaneous border or the volar-ulnar surface. In addition,
      osteotomy widths ranging from 3.5 to 18.1 mm may be performed with the available
      equipment. The complication rate of ulnar shortening is very low, and the overall
      clinical success rate is encouragingly quite high.

PMID- 17536527
TI  - Oblique ulnar shortening osteotomy with a new plate and compression system.
AB  - Ulnocarpal abutment or the ulnocarpal impaction syndrome occurs when excessive
      loads exist between the distal ulna and ulnar carpus. This overloading occurs as
      a result of the distal ulnar articular surface being more distal than the ulnar
      articular surface of the distal radius. This situation has been termed positive
      ulnar variance, and it can quickly lead to ulnar-sided wrist degenerative changes
      and functional losses. Patients often have vague, ulnar-sided complaints of
      chronic pain and swelling with an insidious onset that does not correlate with
      any specific traumatic event. Many procedures have been developed to alleviate
      this condition, but the gold standard for correcting positive ulnar variance is
      the ulnar shortening osteotomy. The goals of the shortening procedure are to
      relieve pain and prevent arthritis by reestablishing a neutral or slightly
      negative ulnar variance. We describe a new plate and compression system in which
      an oblique ulnar diaphyseal osteotomy is both completed and stabilized through
      the same jig-based system.

PMID- 17536528
TI  - Osteochondral shortening osteotomy for the treatment of ulnar impaction syndrome:
      a new technique.
AB  - A new technique for ulna shortening is described. It is a modification of the
      open-wafer procedure that preserves the distal ulna's articular surface. A 4- to
      5-mm chondral-cortical bone block is removed at the distal ulna articular
      metaphysis junction. Closing the bone gap results in the osteotomy site proximal
      to the sigmoid notch. The distal ulna chondral-cortical fragment is secured with
      1 or 2 headless compression screws, which permit early motion and results in
      solid healing. Similar to Feldon's previously described open-wafer procedure,
      this new technique reduces the ulna carpal load by reducing the distal ulna
      carpal length at the distal radioulnar joint. This new technique eliminates the
      exposure of the radiocarpal joint to continuous bleeding from the distal ulna's
      trabecular bone as seen in Feldon's open-wafer procedure and avoids all the
      inherent problems associated with plating the ulna for a typical distal ulna
      osteotomy, such as delayed union and painful hardware.

PMID- 17536529
TI  - Hemiresection of the distal ulna by means of pronator quadratus interposition and
      volar stabilization.
AB  - Surgery for ulnar-sided wrist problems have proved a major challenge. A variety
      of bony procedures, which may or may not be supplemented with soft tissue
      interposition, tenodesis, and fusion of the distal radioulnar joint, have been
      designed in an attempt to address this challenge. The problems encountered in the
      use of these procedures have included weakness, snapping and instability of the
      distal ulna, pain and impaction, nonunion, and regrowth of bone. To address the
      instability of the distal ulna and the radioulnar impaction, we have designed an
      operative technique involving the hemiresection of the distal ulna and the
      interposition of pronator quadratus (volar stabilization of the distal ulna).
      This procedure is a safe method for dealing with pain and loss of function due to
      disorders of the distal radioulnar joint. It provides good pain relief, strength,
      and motion.

PMID- 17536530
TI  - Salvage of the unstable Sauve-Kapandji procedure: a new technique.
AB  - The Sauve-Kapandji procedure has been commonly performed in the setting of
      posttraumatic osteoarthritis of the distal radioulnar joint. A recognized
      complication is instability of the proximal ulnar stump, which may occur in up to
      33% of cases. Salvage of the failed Sauve-Kapandji procedure in this setting is
      difficult and can sometimes involve sacrifice of forearm rotation. We report the
      results of 3 cases of a new salvage procedure in this setting. The radioulnar
      pseudarthrosis was taken down; ulnar continuity was restored with an intercalary
      graft; and forearm rotation was restored with matched hemiresection and
      interposition arthroplasty at the site of previous radioulnar fusion.
      Postoperatively, all patients achieved good forearm rotation (mean supination, 60
      degrees; mean pronation, 65 degrees), had no symptoms of instability, and were
      satisfied with the results of the procedure. Disabilities of the Arm, Shoulder
      and Hand scores improved from preoperative mean of 55 to postoperative mean of
      18.

PMID- 17536531
TI  - Sigmoid notch osseous reconstruction.
AB  - The purpose of this article is to describe a technique of restoring stability or
      congruency to the distal radioulnar joint (DRUJ) by osteoplasty or osteotomy of
      the sigmoid notch, where abnormalities in the osseous anatomy have resulted in
      DRUJ instability. This technique addresses the osseous cause to DRUJ instability
      and avoids the need for complex soft tissue procedures to treat chronic volar
      instability or salvage procedures to treat dorsal instability of the DRUJ
      associated with an impacted fracture of the dorsal rim of the sigmoid notch.

PMID- 17536532
TI  - Ulnar head replacement.
AB  - Recent years have seen an increasing awareness of the anatomical and
      biomechanical significance of the distal radioulnar joint (DRUJ). With this has
      come a more critical approach to surgical management of DRUJ disorders and a
      realization that all forms of "excision arthroplasty" can only restore forearm
      rotation at the expense of forearm stability. This, in turn, has led to renewed
      interest in prosthetic replacement of the ulnar head, a procedure that had
      previously fallen into disrepute because of material failures with early
      implants, in particular, the Swanson silicone ulnar head replacement. In response
      to these early failures, a new prosthesis was developed in the early 1990s, using
      materials designed to withstand the loads across the DRUJ associated with normal
      functional use of the upper limb. Released onto the market in 1995 (Herbert ulnar
      head prosthesis), clinical experience during the last 10 years has shown that
      this prosthesis is able to restore forearm function after ulnar head excision and
      that the materials (ceramic head and noncemented titanium stem), even with normal
      use of the limb, are showing no signs of failure in the medium to long term. As
      experience with the use of an ulnar head prosthesis grows, so does its acceptance
      as a viable and attractive alternative to more traditional operations, such as
      the Darrach and Sauve-Kapandji procedures. This article discusses the current
      indications and contraindications for ulnar head replacement and details the
      surgical procedure, rehabilitation, and likely outcomes.

PMID- 17536533
TI  - Distal radioulnar joint replacement.
AB  - The resection of the ulnar head, as described by Darrach, has unfortunately
      become the standard of care despite the frequent problems of ulnar stump
      instability following this procedure. To offer better treatment to our patients,
      we have to appreciate the various roles and the importance of the ulnar head for
      the function of the distal radioulnar joint (DRUJ) in mechanically loaded forearm
      rotation. The ulnar head forms the load-bearing keystone of the DRUJ and the
      distal forearm, important for maintaining adequate tension within the radioulnar
      ligaments and the interosseous membrane. A DRUJ implant replacing the ulnar head
      should and has to be the fixed point and load-bearing part of the joint and will
      be exerted to large mechanical loads making a neutralization of these forces
      necessary. A partial resurfacing implant for the DRUJ can be used for primary
      procedures. The resection is minimal, and further, the attachments of the
      stabilizing ligaments, the triangular fibrocartilage complex in particular, are
      preserved with a maintained anatomy and stability. For revision and salvage
      procedure, a modular ulnar head can be used, which restores the ulnar head offset
      and stabilizes the ulnar stump, restoring a pain-free DRUJ. The modularity of
      these 2 implants addresses the majority of indications for prosthesis in the
      DRUJ.

PMID- 17536534
TI  - Hemiarthroplasty of the distal ulna with an eccentric prosthesis.
AB  - Replacement arthroplasty of the ulnar head is indicated primarily for stiffness
      and pain as a consequence of rheumatoid, degenerative, and posttraumatic
      arthritis of the distal radioulnar joint. It is also successfully used in the
      setting of previous failed excisional arthroplasty of the distal ulna. A distal
      ulnar hemiarthroplasty, which anatomically recreates the native ulnar head by
      employing an eccentric design, is discussed. The surgical technique includes a
      dorsal approach and careful repair of the soft tissue stabilizers.

PMID- 17536535
TI  - Eclypse: partial ulnar head replacement for the isolated distal radio-ulnar joint
      arthrosis.
AB  - Eclypse is a pyrocarbon spacer that has been developed to substitute the
      articular portion of the damaged ulnar head in patients with an isolated distal
      radioulnar joint degenerative arthritis. The spacer can be inserted without
      significantly detaching the foveal insertion of the triangular fibrocartilage and
      preserving intact the extensor carpi ulnaris sheath. The goal of the implant is
      to maintain adequate separation of the 2 forearm bones throughout the entire
      range of pronosupination. After surgery, the joint stability is supported by the
      joint physiological stabilizers such as the triangular fibrocartilage and
      extensor carpi ulnaris muscle. To avoid dislocation of the implant at the
      extremes of forearm rotation, a titanium stem is implanted into the ulnar distal
      metaphysis with a distal peg inserted in a cylindrical hole in the center of the
      spacer. The loose fitting of the peg into the spacer allows some proximodistal
      translation and slight axial rotation of the implant, enough to adjust its
      position to the always-changing space between the distal ulna and the sigmoid
      notch concavity. Preliminary results in 3 patients are very encouraging, with
      minimal discomfort at the extremes of motion and a mean pronation of 65 degrees
      and supination of 70 degrees. At an average 11 months' follow-up, all patients
      were able to lift up to 4 kg of load throughout the entire range of forearm
      rotation without yielding.

PMID- 17536536
TI  - Fine needle aspiration cytology diagnosis of lymphoid lesions of the orbit.

PMID- 17536537
TI  - Conjunctival changes in children with Kawasaki disease: cytopathologic
      characterization.
AB  - OBJECTIVE: To examine the cytopathological changes in the conjunctiva of patients
      with active Kawasaki disease. STUDY DESIGN: Case-control prospective study.
      Bilateral conjunctival swabs were obtained from 3 groups of children: patients
      with acute KD (11), age-matched controls (7), and patients with inactive KD (9).
      The ThinPrep prepared and Papanicolaou stained smears were examined blindly by 2
      cytopathologists. The cell count differential of cells was performed and recorded
      quantitatively and comparisons between the 3 patient groups were made. RESULTS:
      Only neutrophil counts showed a significant difference among the 3 groups. The
      average scores for the acute KD, control group, and patients with inactive KD
      were 3.5, 1.6 and 1.3, respectively. Using the Pearson chi2 test, the difference
      between the acute KD and the inactive group was statistically significant for
      both eyes (right p = 0.049, left p = 0.004). Samples from acute KD patients were
      more cellular. Neutrophils surrounding conjunctival epithelial cells, or
      "neutrophilic rosetting", were seen in 4 (36%) cases of the active disease group
      but not in the other groups. CONCLUSION: "Neutrophilic conjunctivitis" is
      characteristic in patients of acute KD that may be of value in the initial
      evaluation and subsequent follow-up of KD patients.

PMID- 17536538
TI  - Cytologic characteristics of subependymal giant cell astrocytoma in squash
      smears: morphometric comparisons with gemistocytic astrocytoma and giant cell
      glioblastoma.
AB  - OBJECTIVE: To evaluate the squash smear features of subependymal giant cell
      astrocytoma (SEGA) in comparison with gemistocytic astrocytoma and giant cell
      glioblastoma. STUDY DESIGN: We compared the squash smear features of 3 cases of
      SEGA, 9 cases of gemistocytic astrocytoma and 3 cases of giant cell glioblastoma
      with the morphometric findings. RESULTS: SEGA had, on average, a 15.84 +/- 5.03
      microm nucleus, 33.22 +/- 12.05-microm cytoplasm and 0.50 +/- 0.12
      nuclear/cytoplasmic ratio in squash smears. In addition, SEGA showed hairlike
      processes distributed along the squash direction like strap cells. While the
      gemistocytic astrocytoma had several tumor cells showing a vertically located
      nucleus, the tumor cells of SEGA showed nuclei oriented mainly in parallel.
      CONCLUSION: These squash cytologic features of SEGA can be very helpful in the
      differential diagnosis by excluding mimics.

PMID- 17536539
TI  - Fine needle aspiration cytology in cutaneous and subcutaneous endometriosis.
AB  - OBJECTIVE: To study the role of fine needle aspiration cytology (FNAC) in the
      diagnosis of cutaneous and subcutaneous endometriosis. STUDY DESIGN: We present 7
      cases of endometriosis in abdominal wall, inguinal region and perineum diagnosed
      by FNAC. All cases were confirmed with histologic follow-up. Cytologic and
      histologic material was prepared using standard methods. RESULTS: The smears were
      highly cellular, showing a hemorrhagic background with hemosiderin-laden
      macrophages and sheets of epithelial and stromal cells. Occasionally, these
      cellular components were closely associated. CONCLUSION: FNAC is useful in the
      diagnosis of cutaneous and subcutaneous endometriosis, providing a rapid and
      accurate preoperative diagnosis.

PMID- 17536540
TI  - Fine needle aspiration cytolog of perineal alveolar rhabdomyosarcoma:
      cytohistopathologic and immunocytochemical correlations.
AB  - OBJECTIVE: To describe the cytopathologic findings in a case of alveolar
      rhabdomyosarcoma (ARMS) of the perineum in a 13-year-old girl and to compare the
      cytopathologic findings with the histopathologic and immunohistochemical features
      observed on the corresponding fragments obtained from core biopsy of the mass.
      STUDY DESIGN: The cytopathologic findings observed in fine needle aspiration
      biopsy of a vulvar mass were analyzed with reference to their predictive
      diagnostic value in pathologic evaluation of the lesion. RESULTS: Following a
      prospective cytopathologic diagnosis of ARMS, a cutting needle core biopsy was
      performed. Histopathologic and immunohistochemical study of the tissue fragments
      confirmed the cytopathologic diagnosis. CONCLUSION: Careful cytopathologic
      evaluation of optimal cell samples from ARMS may elicit a correct diagnosis
      provided that immunocytochemical staining for markers of myogenic differentiation
      is performed in a pretherapeutic phase.

PMID- 17536541
TI  - Fine needle aspiration cytology and flow cytometry in the diagnosis and
      subclassification of non-Hodgkin's lymphoma based on the World Health
      Organization classification.
AB  - OBJECTIVE: To determine the usefulness of fine needle aspiration cytology (FNAC)
      in combination with flow cytometry on the new World Health Organization (WHO)
      classification of malignant lymphoma. STUDY DESIGN: Smears and flow cytometry
      reports of patients who underwent both methods at the same time were
      independently examined. Both methods were classified according to the new WHO
      classification of malignant lymphoma. RESULTS: A group of 131 smears were
      examined. In 89 cases exact diagnosis was made by cytomorphology. Twenty-five
      cases were not classified exactly or were classified incorrectly, resulting in a
      sensitivity of 96.4% and a specificity of 85%. With flow cytometry, only 30 of
      131 patients could be classified exactly, resulting in a sensitivity of 27% and
      specificity of 100%, respectively. The combination of methods showed a
      sensitivity of 85% and specificity of 100%. CONCLUSION: The combination of FNAC
      and flow cytometry obtained by FNAC can distinguish between benign and malignant
      lymphoid infiltrates and support a diagnosis of lymphoma.

PMID- 17536542
TI  - Effectiveness of liquid-based cytology and papanicolaou tests in a low risk
      population.
AB  - OBJECTIVE: To compare sensitivity an effectiveness of ThinPrep vs. Pap Test and
      determine whether the Hybrid Capture System II (HCII) for detection of human
      papillomavirus (HPV) could increase the sensitivity and effectiveness of cervical
      screening in a low risk population. STUDY DESIGN: We present a comparative
      observer, blind, "split sample" study of ThinPrep and Papanicolaou staining in a
      population of 2026 consecutive women. RESULTS: Conventional Papanicolaou stain
      detected lesions in 62 cases (3.06%), including 1 atypical glandular cell of
      undetermined significance (AGUS), 34 atypical squamous cells of undetermined
      significance (ASCUS) (1.73% of atypias), 20 (0.99%) low grade squamous
      intraepithelial lesions (LSIL), and 7 (0.35%) high grade squamous intraepithelial
      lesions (HSIL). ThinPrep detected lesions in 63 cases (3.11%), including 26
      (1.28%) ASCUS, 27 (1.33%) LSIL and 10 (0.49%) HSIL. Despite this overall
      similarity, only 35 had a coincident cytopathologic result by both methods. The
      kappa concordance index between ThinPrep and Pap was 0.546. Sensitivity and
      specificity were 74.6 and 45.0 in ThinPrep and 69.5 and 25.0 in Papanicolaou
      stained smears. High risk HPV (HR-HP 17) was positive in 13 of ZOASCUS and in 21
      of 22 SIL. CONCLUSION: Technologies now widely available such as Thin Prep and
      viral detection aim to improve accuracy of screening.

PMID- 17536543
TI  - Evaluation of pregnancy-related cells in endometrial cytology.
AB  - OBJECTIVE: To determine the significance of pregnancy-related cells in
      endometrial smears. STUDY DESIGN: Pregnancy-related cells in 4429 endometrial
      smear samples were retrospectively analyzed and evaluated for clinicopathologic
      and cytomorphologic features. RESULTS: Of the 4429 endometrial smears taken for
      cancer screening, pregnancy-related cells were detected in 12 cases (0.3%). They
      were estimated cytologically as negative or suspicious and confirmed as cases
      ofspontaneous abortion (8 cases), placental site nodule (3 cases), and partial
      hydatidiform mole (1 case). Decidual cells were observed in all cases, and some
      of these showed atypia. Trophoblasts were observed in 5 (41.7%) of the 12 cases.
      Syncytiotrophoblasts were observed in 1 case (8.3%) and nonsyncytiotrophoblasts
      in 5 (41.7%) of the 12 cases. Pregnancy-related cells were observed in an
      endometrial smear in 7 cases; other cases were missed during cytologic
      examination and were retrospectively identified. CONCLUSION: Pregnancy-related
      cells are likely to be missed because they are difficult to identify or are
      surrounded by a cluster of endometrial cells. The decidual cell is a key cell for
      the cytologic diagnosis of pregnancy-related cells. Determining the existence of
      pregnancy-related cells in endometrial smears is important for the further
      assessment of patients and the differential diagnosis of several endometrial
      lesions.

PMID- 17536544
TI  - Weak telomerase activity in malignant cells in metastatic serous effusions:
      correlation to short survival time.
AB  - OBJECTIVE: The purpose of this study was to evaluate whether the intensity of
      telomerase activity measured on the cellular level in effusions correlates to
      survival time in cases of metastatic spread to the serous cavities. STUDY DESIGN:
      Telomere repeat amplification protocol (TRAP) in situ was applied to 46 effusions
      containing metastatic cancer cells. RESULTS: Weak telomerase activity in tumor
      cells was seen in 7 cases, and moderate or strong activity in 39 cases. The
      intensity of the enzyme activity correlated significantly to survival (Kaplan
      Meier survival analysis), the median survival time being 18 days for patients
      with weakly positive tumors and 100 days for patients with moderately or strongly
      positive tumors (Kruskal-Wallis test, p = 0.021). CONCLUSION: The strong
      relationship between telomerase activity in tumor cells in effusions and survival
      time has never been described before. Determination of telomerase activity on the
      cellular level provides a way to identify a subgroup of patients with a high
      probability of short survival.

PMID- 17536545
TI  - Fine needle aspiration cytology of primary lymphoid lesions of the orbit: report
      of four cases.
AB  - BACKGROUND: The role offine needle aspiration cytology (FNAC) in diagnosis and
      differentiation of primary orbital lymphoid lesions is debatable, and little
      literature exists on cytodiagnosis of orbital lymphoid lesions. CASES: Four
      patients with orbital lesions underwent routine FNAC. In 3 cases, histopathologic
      examination was performed with immunohistochemistry (IHC). Cytologic features and
      diag- noses were correlated with histopathologic diagnoses. Two were
      cytologically diagnosed with low-grade non-Hodgkin lymphoma (NHL) and 2 with
      pseudolymphoma and inflammatory pseudotumor, respectively. Of the 2 cases of
      histologically diagnosed NHL, 1 had concordant diagnosis and the other had a
      jalse negative diagnosis of pseudolymphoma; both showed significant increase in
      mast cells, with neoplastie lymphoid cells exhibiting a higher N:C ratio and
      coarser chromatin texture. The case cytologically interpreted as suspicious for
      NHL was identified as a psetedolymphoma on histology (false positive). The case
      of inflammatory pseudotumor, in which hiopiy was not peiformned, responded well
      to corticosteroids, strengthening the cytologic diagnosis. CONCLUSION: FNAC
      diagnosis and differentiation of benign vs. malignant primacy orbital lymphoid
      lesions is often difficult. Careful cytologic interpretation with respect to
      certain subtle cytologic details is needed in minimizing false positive or false
      negative diagnoses. In difficult situations, IHC using suitable immunomarkers
      proves highly useful.

PMID- 17536546
TI  - Kaposi's sarcoma of the thyroid gland in an HIV-negative woman: a case report.
AB  - BACKGROUND: Kaposi's sarcoma (KS) is a neoplastic disease that affects primarily
      the skin, but visceral involvement is not uncommon. Most of the cases are seen in
      AIDS patients and transplant recipients; however, rare HIV-negative cases have
      also been reported. Involvement of the thyroid is exceedingly rare, with only a
      fw cases reported, all of them associated with AIDS. CASE: A 45-year-old, black,
      Haitian woman presented with a slowly enlarging left side of the thyroid.
      Computed tomography showed multiple thyroid nodules, and there was no uptake of
      iodine on the nuclear scan. Fine needle aspiration of the lesion was performed.
      The smears were composed of spindle and plasmacytoid cells, which raised the
      possibility of medullary carcinoma. The patient underwent left hemithyroidectomy.
      Histologic examination showed KS in the thyroid. CONCLUSION: We present the first
      case of KS of the thyroid in a HIV-negative patient. Familiarity with the
      cytologic features can be useful in making the diagnosis.

PMID- 17536547
TI  - Pseudomycetoma for microsporum canis: report of a case diagnosed by fine needle
      aspiration biopsy.
AB  - BACKGROUND: Fine needle aspiration biopsy (FNAB) of the skin is useful in
      subcutaneous lesions. Dermatophytes are almost exclusively superficial cutaneous
      mycoses and constitute 70-80% of all mycoses and 5% of dermatologic
      consultations. Inflammatory and invasive forms, as well as infections that remain
      in chronic forms or persist in spite of treatment, are more frequent in
      immunocompromised individuals. The clinicalpresentations of these invasive cases
      are dermatopbytic granulomas (granuloma of Wilson-Majocchi and pseudomycetoma) or
      Hadida's disease. CASE: A 17-year-old male with an 8-year history of tinea
      capitis and multiple kerion lesions in the occipital region, left foot and right
      elbow resistant to conventional treatment was diagnosed by KOH tests and cultures
      as Microsporum canis. Two months before consultation he noticed the slow growth
      of a subcutaneous nodule in the base of the neck. FNAB of the neck nodule was
      performed. The diagnosis of pseudomycetoma by Microsporum canis was made.
      CONCLUSION: We report a case of pseudomycetoma caused by Microsporum canis, with
      the diagnosis made by FNAB. This case appears to be the first one diagnosed by
      this method in a human.

PMID- 17536548
TI  - Metastatic ganglioneuroblastoma in head and neck diagnosed by fine needle
      aspiration: a case report.
AB  - BACKGROUND: To describe the cytologic findings of a case of ganglioneuroblastoma
      metastatic to the jaw and neck. CASE: A 15-year-old boy with a known case of
      ganglioneuroblastoma of the kidney for the previous 10 years manifested by right
      mandibular and neck masses on 2 occasions 1 year apart was diagnosed with
      metastatic ganglioneuroblastoma by fine needle aspiration (FNA). FNA showed
      neurofibrillary material, small malignant cells, Homer-Wright rosettes.
      mononucleated, binucleated and multinucleated ganglion cells and Reed Sternberg
      like ganglion cells. Metastatic ganglioneuroblastoma was diagnosed on both
      occasions, and the patient received appropriate treatment, with resolution of the
      lesions. CONCLUSION: This case illustrates the FNA findings of metastatic
      ganglioneuroblastoma in the head and neck region.

PMID- 17536549
TI  - Retroperitoneal extramedullary anaplastic plasmacytoma masquerading as sarcoma:
      Report of a case with an unusual presentation and imprint smears.
AB  - BACKGROUND: Extramedullary plasmacytoma of the retroperitoneum is rare.
      Furthermore, plasmacytoma with anaplastic features can be confused with high
      grade sarcoma clinically and histologically, particularly when the initial
      immunohistochemical tumor markers are negative. However, paying attention to
      cytologic imprint smears can give valuable clues to the correct diagnosis. CASE:
      A 73-year-old male was admitted to our hospital with a recent history of back
      pain. Abdominal computed tomography revealed a large retroperitoneal mass (6.8 x
      5.1 cm). The initial pathologic evaluation revealed a high grade pleomorphic
      neoplasm that failed to express multiple epithelial, mesenchymal, lymphoid and
      melanoma immunohistochemical markers. Subsequent fresh tissue evaluation with
      touch imprints and immunophenotypic characterization confirmed the plasma cell
      origin of the tumor. Thorough retrospective review of the touch imprint smears
      clearly showed the plasmacytic cytologic features. Features of multiple myeloma
      were essentially absent. CONCLUSION: Performing cytologic imprint smears on fresh
      tissue material may help in making the correct diagnosis and is highly
      recommended.

PMID- 17536550
TI  - Diagnosis of pediatric genitourinary embryonal rhabdomyosarcoma by urine
      cytology: a case report.
AB  - BACKGROUND: Urinary cytology is an uncommon investigative tool for pediatric
      tumors. CASE: A 16-month-old infant presented for investigation ofhematuria and
      blood clots into diapers. Urinary cytology showed a population of small, round,
      blue cells with little cytoplasm and high nuclear/cytoplasmic ratios. The cells
      were positive for desmin and negative for cytokeratin. A cytologic diagnosis of
      embryonal rhabdomyosarcoma was offered and subsequently confirmed by
      histopathology. CONCLUSION: Embryonal rhabdomyosarcomas are not uncommon in the
      pediatric population. Urinary cytology may be useful for rapid diagnosis and
      early management of such cases.

PMID- 17536551
TI  - Mediastinal pleomorphic liposarcoma diagnosed by fine needle aspiration biopsy: a
      case report.
AB  - BACKGROUND: Progress in radiology and pathology for diagnosing mediastinal tumors
      has R been made in recent decades, thanks to the use of fine needle aspiration
      biopsy (FNAB) guided by computed tomography, which has replaced mediastinoscopy
      and open biopsies. CASE: A 66-year-old male had a history o productive coughing
      with mucopurulent expectoration, progressive dyspnea, arthralgias, myalgias,
      astenia and adynamia for the previous 3 months. A CT scan and magnetic resonance
      imaging revealed a poorly limited tumor mass ofheterogeneous den sity in the
      anterior mediastinum. FNAB of the tumor mass showed malignant cells compatible
      with liposarcoma. CONCLUSLON: Of the several types of mesenchymal mediastinal
      neoplasms, liposarcoma is the most important. Many of them are seen in adults,
      and <10 cases have been diagnosed in children. The symptoms are related to
      compression of the nearby airways. Usually liposarcomas are yellow, lobed tumors
      without capsules that infiltrate adjacent organs and tissues. Microscopically,
      they have the same histologic spectrum as tumors originating in other sites.
      Thus, it is common to observe all the histologic varieties of soft tissue
      liposarcomas. The identification of lipoblasts is the key to the correct
      diagnosis in FNAB material.

PMID- 17536552
TI  - Primary osteogenic sarcoma of the breast: cytomorphologic study of 3 cases with
      histologic correlation.
AB  - BACKGROUND: Primary osteogenic sarcomas of the breast are extremely rare
      neoplasms. The histologic and cytologic features are comparable to those of their
      soft tissue and skeletal counterparts. To assess the utility of fine needle
      aspiration (FNA) in preoperative identification of osteogenic sarcomas, we
      retrospectively reviewed the FNA findings of 3 cases diagnosed in our hospital
      over 2 1/2 years. CASES: Three women, aged 48, 55 and 76 years, presented with a
      palpable lump of a few months' duration in their breasts. FNA was indicative of
      malignancy, and mastectomy with ipsilateral axillary lymph node dissection was
      performed. The cytologic features were of hypocellular or hypercellular smears
      with pleomorphic cells; scarce or abundant metachromatic amorphous material,
      suggestive of osteoid; osteoclast-like giant cells; and stromal fragments.
      CONCLUSION: Although cytologic features can be suggestive of osteosarcoma in the
      appropriate clinical setting, prompt preoperative diagnosis of malignancy in FNA
      samples of these tumors can avoid undertreatment, because mammographic and
      clinical findings are in many cases confused with the features of a benign
      lesion, more specifically calcified fibroadenoma.

PMID- 17536553
TI  - Sarcomatoid renal cell carcinoma metastatic to the breast: report of a case with
      diagnosis on fine needle aspiration cytology.
AB  - BACKGROUND: Tumors metastatic to the breast are a rare occurrence. The correct
      identification is essential as there are divergent management implications. Fine
      needle aspiration cytology (FNAC) is an effective method of diagnosis when
      coupled with the judicious use of immunocytochemistry. CASE: A 50-year-old Indian
      woman presented with a palpable right breast lump that was clinically suspicious
      for malignancy. There were no contralateral breast masses or palpable axillary
      lymphadenopathy. There was a history of nephrectomy carried out several years
      earlier for renal cell carcinoma (RCC). FNAC of the right breast lump yielded
      malignant epithelioid and occasionally spindled cells within an inflamed
      background, while immunocytochemistry showed positive reactivity of tumor
      cellsfor CD10, with negative staining for CK7. The cytologic diagnosis favored a
      tumor of renal origin. The patient underwent wide central excision of the right
      breast lump, whereby the diagnosis of metastatic RCC with sarcomatoid features
      was confirmed. On follow-up, she developed metastases to multiple organ sites and
      died. CONCLUSION: A high index of suspicion is required in the diagnosis of
      disease metastatic to the breast. FNAC is a reliable diagnostic tool in the
      distinction of metastasis from primary malignancy of the breast.

PMID- 17536554
TI  - Fine needle aspiration cytology in mediastinal myxoid liposarcoma: a case report.
AB  - BACKGROUND: The mediastinum is an uncommon site for liposarcoma, with <1 % of all
      tumors occurring in this site. CASE: A 40-year-old woman presented with superior
      vena caval syndrome. Radiologic investigations revealed the presence of a large
      soft tissue mass occupying the anterior and middle mediastinum. A computed
      tomography (CT)-guided fine needle aspiration cytology (FNAC) sample showed the
      presence of fibrillary myxoid material with arborizing blood vessels and atypical
      lipoblasts. A diagnosis of myxold liposarcoma was made, which was later confirmed
      on bistopathology. CONCLUSION: The mediastinum is a challenging area for FNAC,
      which is a useful tool for accurate diagnosis. Awareness of the presence of
      liposarcoma is important for its recognition.

PMID- 17536555
TI  - Tubercular orchitis in a patient with AIDS: report of a case with fine needle
      aspiration diagnosis.
AB  - BACKGROUND: Although tuberculosis is one of the most common opportunistic
      infections in AIDS, the testis is rarely involved. Clinically, tubercular
      orchitis mimics malignancy. Fine needle aspiration (FNA) can be used to
      distinguish these 2 lesions. CASE: A 34-year-old, heterosexual male presented
      with right scrotal swelling, loss of weight and fever. Clinically, malignancy was
      suspected. FNA showed a few lymphocytes and neutrophils in a necrotic background.
      Ziehl-Neelsen staining showed high acid-fast bacillus positivity. Serologic
      testing for HIV showed seropositivity for HIV I and II antibodies. CONCLUSION:
      FNA is a useful modality in differentiating tuberculosis from malignancy. In
      developing countries, tuberculosis should be considered in cases of unilateral
      testicular enlargement. To the best of our knowledge, this is the third reported
      case of AIDS presenting as testicular tuberculosis.

PMID- 17536556
TI  - Fine needle aspiration cytology of low grade endometrial stromal sarcoma: a case
      report.
AB  - BACKGROUND: Endometrial stromal sarcoma (ESS) is a rare neoplasm and is composed
      of E cells closely resembling normal proliferative endometrial stromal cells.
      Because of its rarity, the preoperative diagnosis is difficult for clinicians.
      These tumors are rarely subjected to fine needle aspiration (FNA), and the
      cytologic diagnosis is also difficult, as the differential diagnosis is
      leiomyosarcoma/cellular leiomyoma. CASE: A 23-year-old woman presented with a
      history of prolonged vaginal bleeding. The diagnosis on FNA was given as sarcoma
      with the possibility of low grade ESS or leiomyosarcoma. On histopathologic
      examination, the diagnosis was confirmed to be low grade ESS. CONCLUSION:
      Aspirates of low grade ESS are extremely cellular, with cohesive tissue fragments
      of monotonous, small, oval cells with bland chromatin tightly women in a
      metachromatic, extracellular matrix. The differential diagnosis should include a
      cellular leiomyoma and leiomyosarcoma.

PMID- 17536557
TI  - Metanephric adenoma vs. Wilms' tumor: a report of 2 cases with diagnosis by fine
      needle aspiration and cytologic comparisons.
AB  - BACKGROUND: Metanephric adenoma (MA) is a rare benign renal neoplasm that can
      occur at any age, whereas, Wilms' tumor (WT) is the most common malignant renal
      neoplasm in children and is occasionally seen in adults. CASES: In case 1, a 26
      year-old male had a left renal mass. Fine needle aspiration (FNA) showed 3
      dimensional sheets of cells with nuclear overlapping, molding, irregular nuclear
      membrane and distinct nucleoli. Frequent mitotic figures could be seen. The
      cytologic differential diagnosis included Wilms' tumor, neuroectodermal tumor and
      metanephric adenoma. Nephrectomy revealed Wilms' tumor. In case 2, a 24-year-old
      female presented with erythrocytosis and a right renal mass. FNA showed small,
      uniform cells with smooth nuclear membrane, fine chromatin and inconspicuous
      nucleoli. A diagnosis of metanephric adenoma was made and confirmed on
      nephrectomy. CONCLUSION: Differentiating MA from WT based on cytologic features
      on FNA biopsy prior to surgical resection can he difficult.

PMID- 17536558
TI  - Cytologic features of metanephric adenoma of the kidney during pregnancy: a case
      report.
AB  - BACKGROUND: Metanephric adenoma (MA) is a relatively rare neoplasm derived from
      metanephric blastema and composed of well-differentiated epithelial nephroblastic
      cells. In view of its invariably benign clinical outcome, a preoperative
      diagnosis of this tumor could be of critical importance. Since computed
      tomography and ultrasound imaging are not per se sufficient to unequivocally
      distinguish between MA and malignant neoplasms, fine needle aspiration cytology
      (FNAC) could be the only accurate method to establish a preoperative diagnosis of
      this tumor. However, cytologic appearance of MA is not well characterized. CASE:
      A 33-year-old pregnant woman presented with erythrocytosis. Transabdominal
      ultrasound examination disclosed a mass in her left kidney. FNA smears showed
      small, uniform cells with bland nuclei arranged in compact acinar and follicular
      structures; immunocytochemical staining revealed a diffuse, positive reaction for
      CD57, WT-1 and vimentin, and epithelial membrane antigen and alpha-methylacyl-CoA
      racemase yielded negative results. These cytologic and immunocytochemicalfindings
      led to a preoperative diagnosis of MA. After delivery, the diagnosis was
      confirmed on the surgical specimen. CONCLUSION: A diagnosis of MA could be
      established by FNAC supported by immunocytochemical analysis. The present case
      illustrates the clinical impact that this diagnosis could have on patient
      management.

PMID- 17536559
TI  - Deep-seated congenital juvenile xanthogranuloma: report of a case with emphasis
      on cytologic features.
AB  - BACKGROUND: Juvenile xanthogranuloma (JXG) is a rare, benign non-Langerhans cell
      histiocytosis that usually occurs in the head, neck or upper trunk of neonates
      and young children. Lesions appear most frequently as solitary cutaneous nodule,
      but in 12% of cases they are multiple and in 5%, subcutaneous or deep-seated. In
      4% of cases they are systemic. Histopathologically, deep lesions tend to be more
      cellular and monotonous, with fewer Touton cells. Independent of its location,
      the prognosis is excellent, even after incomplete resection. The lesions usually
      resolve spontaneously within 3 years of diagnosis. CASE: A child was born with a
      large, deep-seated cervical mass that was initially evaluated by fine needle
      aspiration biopsy, which disclosed vague, granulomatous aggregates with
      monotonous, histiocytic CD68-positive cells. The surgical specimen histology
      revealed a JXG with skeletal muscle invasion. Complete reexcision was performed 2
      months later after regrowth of the tumor. CONCLUSION: Deep-seated neonatal JXGs
      are infrequent and may demonstrate aggressive behavior. In this setting fine
      needle aspiration cytology is a useful tool for the initial differential
      diagnostic procedure and management.

PMID- 17536560
TI  - Primary leiomyosarcoma of the inferior vena cava: report of a case diagnosed by
      fine needle aspiration cytology and confirmed by histopathologic examination.
AB  - BACKGROUND: Leiomyosarcoma is a malignant neoplasm and can originate within major
      abdominal veins, including the inferior venacava (IVC). CASE: A 45-year-old woman
      presented with upper abdominal pain and a mass lesion in the liver and within the
      lumen of the IVC. A diagnosis of primary leiomyosarcoma of the IVC was made by
      using imaging techniques,fine needle aspiration cytology and histopathologic
      examination of the resected specimen. CONCLUSION: In patients presenting with
      vague upper abdominal pain and radiologic features of a hepatic mass extending to
      major veins, the rare possibility of primary leiomyosarcoma of the IVC shoald he
      considered and investigated by both fine needle aspiration cytology and
      intraoperative histology. Early surgical intervention and/or postoperative
      chemotherapy and radiotherapy are associated with improved survival.

PMID- 17536561
TI  - Pulmonary langerhans cell histiocytosis (histiocytosis X) on bronchoalveolar
      lavage: a report of 2 cases.
AB  - BACKGROUND: Pulmonary Langerhans cell histiocytosis (PLCH) is an interstitial
      lung disease characterized by bilateral nodular and cystic lesions. Clinically it
      seems to be a reactive process related to cigarette smoking. CASES: In 2 cases of
      PLCH, cytologic and immunocytochemical evaluation of bronchoalveolar lavage (BAL)
      fluid was successfully used for the diagnosis of PLCH. Two heavy smokers
      complained of fever, cough and debilitation. Serologic and hematologic values
      were normal. In both cases radiography and computed tomography (CT) were similar,
      showing multiple bilateral nodular or cystic lesions in the middle and upper lung
      zones. Cytospins obtained from BAL were Papanicolaou and May-Grunwald-Giemsa
      stained; others were immunostained with cytokeratin cocktail, CD1a and S-100.
      Cytospins showed a monomorphous and dispersed cell population consisting
      ofmononucleated or binucleated and occasionally multinucleated histiocytes.
      Single cells showed wide, well-defined, acidophilic cytoplasm and oval or kidney
      shaped, vesicular nuclei with irregular shapes, evident nucleoli and frequent
      grooves and indentations. Immunocytochemical staining showed diffuse cytoplasmic
      positivity for S-100 and CD1a and negativity for cytokeratin; only the few
      cylindrical cells present in the cytospins were positive for cytokeratin. In both
      cases the cytologic diagnosis of PLCH was confirmed by subsequent CT and clinical
      follow-up. CONCLUSION: Cytologic and immunocytochemical evaluation of BAL fluid
      permits a definitive diagnosis of PLCH. This cytologic diagnosis is clinically
      relevant because it permits surgical biopsy to be bypassed and allows waiting for
      a possible spontaneous or pharmacologic resolution.

PMID- 17536562
TI  - Fine needle aspiration of a subcutaneous mass caused by metastatic transitional
      cell carcinoma.

PMID- 17536563
TI  - Cytomorphology of cells on conventional cervical smears from HIV-infected women.

PMID- 17536564
TI  - Polarizing light microscopy for identifying chondroid tissue in aspirates of
      pleomorphic adenoma.

PMID- 17536565
TI  - Tuberculoid morphology in borderline lepromatous leprosy.

PMID- 17536566
TI  - Cytologic appearance of ureteral stenosis caused by polyomavirus.

PMID- 17536567
TI  - Interobserver agreement in the interpretation of chromogenic in situ
      hybridization for detection of human papillomavirus in gynecologic cytology: an
      appraisal of 55 cases.

PMID- 17536568
TI  - RNA quality comparison of preservative media in lung fine needle aspirate
      specimens for standardized StaRT polymerase chain reaction transcript abundance
      measurement to enhance the cytomorphologic diagnosis of lung cancer.

PMID- 17536569
TI  - Elastofibroma: cytologic findings using fine needle aspiration.

PMID- 17536570
TI  - Fine needle aspiration of a breast mass in visceral leishmaniasis.

PMID- 17536571
TI  - Preserving a legacy. Interview by Will Sullivan.

PMID- 17536572
TI  - Covering the uncovered.

PMID- 17536573
TI  - Critiquing cardio workouts.

PMID- 17536574
TI  - Daniel Callahan redux--business and medicine, "can this marriage work?".

PMID- 17536575
TI  - The modern plague.

PMID- 17536576
TI  - Nuclear power and cancer in an oil-dependent country.

PMID- 17536577
TI  - To participate or not in the physician quality reporting initiative (PQRI); that
      is the question.
AB  - The Tax Relief and Health Care Act of 2006 authorized the establishment of a
      physician quality reporting system which would tie a reimbursement incentive to
      compliance with benchmarks that are considered proxies of quality patient care.
      The Centers for Medicare and Medicare Services (CMS) has called this the
      Physician Quality Reporting Initiative (PQRI). A brief historical background
      about how this program evolved, how one participates in this initiative, and the
      strengths and weaknesses of current and new benchmarks is presented.

PMID- 17536578
TI  - Unusual presentation of spontaneous splenic rupture.
AB  - We report a case of a 47-year-old man who presented with hypotension after 2
      weeks of fatigue and upper respiratory infection symptoms, and rapidly
      deteriorated in the emergency department. A bedside ultrasound revealed free
      intraperitoneal fluid, a subsequent diagnostic peritoneal lavage showed
      hemoperitoneum, and a laparotomy confirmed a splenic rupture. Pathology results
      revealed a relatively rare form of leukemia, known as hairy cell leukemia,
      leading to this presentation. We discuss the differential diagnosis of
      spontaneous (or without antecedent trauma) splenic rupture with a review of hairy
      cell leukemia, and stress the importance of keeping a high index of suspicion for
      medical diseases that affect the spleen.

PMID- 17536579
TI  - Balance in the balance. Protecting your life.

PMID- 17536580
TI  - Think, then write! A few minutes of thought can be a great investment.

PMID- 17536581
TI  - Sit up for a pulse. When congestive heart failure fells the boss, well-meaning
      colleagues make a bad situation worse.

PMID- 17536582
TI  - Physician certification for medical necessity. Is it worth the paper it's written
      on?

PMID- 17536584
TI  - Just say no to personals cell phones on ambulances.

PMID- 17536583
TI  - Resuscitation of a child following a near-drowning.

PMID- 17536585
TI  - Personal cell phones have their uses in EMS.

PMID- 17536586
TI  - Billing basics. Top tips to ensure you see the money.

PMID- 17536587
TI  - Teaching street smarts. The challenge of delivering realistic training.

PMID- 17536588
TI  - Talking with text. With your presentations, a little is plenty.

PMID- 17536590
TI  - Chicago's OEMC: a unified approach to first response.

PMID- 17536589
TI  - Reconciling fractured communications data. A response to the IOM report.

PMID- 17536591
TI  - Dreaming up an interactive ambulance.

PMID- 17536592
TI  - ED information technology: what's it mean for EMS?

PMID- 17536593
TI  - Telemedicine becoming reality for prehospital EMS.

PMID- 17536594
TI  - At times like this: telemedicine comes to the country.

PMID- 17536595
TI  - Room to grow: How to optimize the spectrum for public-safety broadband.

PMID- 17536596
TI  - Coping with violent people: a multi-part series.

PMID- 17536597
TI  - Beyond the basics: street drugs.

PMID- 17536598
TI  - Evolution of all-cause, cardiovascular and cancer mortality rates in the age
      class of 85 years and above. Period 1950-2000.

PMID- 17536599
TI  - Prevalence of obesity, physical inactivity and undernutrition, a triple burden of
      diseases during transition in a developing economy. The Five City Study Group.
AB  - OBJECTIVE AND DESIGN: The objective of the study was to find out the prevalence
      of overweight, obesity, undernutrition and physical activity status in the urban
      populations of India. Cross-sectional surveys were conducted in 6-12 urban
      streets in each of five cities in five different regions of India using a common
      study protocol and criteria of diagnosis. SUBJECTS AND METHODS: A total of 6940
      subjects (3433 women and 3507 men) aged 25 years and above were randomly selected
      from the cities of Moradabad (n = 2002),Trivandrum (n = 1602), Calcutta (n =
      900), Nagpur (n = 894) and Bombay (n = 1542). Evaluation and validation were
      performed by a physician and dietitian-administered questionnaire at Moradabad.
      After pooling of data, all subjects were divided into various age groups for men
      and women. Obesity (body mass index = 30 > kg/m(2)) and overweight (BMI 2 25-29.9
      kg/m(2) and > 23 kg/m(2)) as well as waist-hip ratio (> 0.85 in women and > 0.88
      in men, central obesity) were calculated and physical activity status assessed by
      a validated questionnaire. RESULTS: The overall prevalence of obesity was 6.8%
      (7.8 vs. 6.2%, P < 0.05) and overweight 33.5% (35.0 vs. 32.0%, P < 0.05) among
      women and men, respectively. The highest prevalence of obesity (7.8%) and
      overweight (36.9%) was found among subjects aged 35 to 44 years in both sexes.
      The prevalence of obesity was significantly (P < 0.05) greater in Trivandrum
      (8.5%), Calcutta (7. 1%) and Bombay (8.3%) compared to Moradabad (6.2%) among
      women and in Trivandrum (7.4%) and Bombay (7.2%), compared to Nagpur (5.0%) among
      men. There was a significant decreasing trend in obesity (P < 0.05) and
      overweight (P < 0.05) with increasing age above 35-44 years in both sexes. The
      overall prevalence of subjects > 23 kg/m(2) was 50.8% and central obesity 52.6%.
      The overall prevalence of sedentary behaviour was 59.3% among women and 58.5%
      among men. Both sedentary behaviour and mild activity showed a significant
      increasing trend in women after the age of 35-44 years. In men, such a trend was
      observed above the age of 45 years. Sedentary behaviour was significantly (P <
      0.05) greater in Trivandrum, Calcutta, and Bombay compared to Nagpur. Sedentary
      behaviour was significantly (P < 0.001) associated with obesity in both sexes,
      compared to non-obese men and women. The overall prevalence of undernutrition was
      5.5% (n = 380) which was significantly more common in Moradabad, north and
      Nagpur, central India compared to other cities. CONCLUSIONS: Obesity, overweight
      and central obesity and sedentary behaviour coexist with undernutrition, and have
      become a public health problem in all the five cities of India. The prevalence of
      obesity and sedentary behaviour was significantly greater in Trivandrum, Calcutta
      and Bombay compared to Moradabad and Nagpur. Sedentary behaviour was
      significantly associated with obesity compared to non-obese subjects in both
      sexes, which may be due to greater economic development in metro cities.

PMID- 17536600
TI  - Evaluation of children with a large pericardial effusion and cardiac tamponade.
AB  - OBJECTIVES: Large pericardial effusions and cardiac tamponade are rare in
      childhood. The aim of this study was to evaluate the aetiological factors and
      clinical findings of large pericardial effusion and cardiac tamponade in
      children. METHODS: We reviewed retrospectively the records of 10 (6 male, 4
      female) patients (mean age: 8.05 +/- 4.4 y) with the diagnosis of large
      pericardial effusion and cardiac tamponade requiring pericardiocentesis and
      pericardial drainage between 2002 and 2004. RESULTS: After extensive diagnostic
      investigation we detected that three patients had tuberculosis, one patient had
      uraemic pericarditis; one patient had bacterial pericarditis; one patient had
      post-pericardiotomy syndrome; two patients had malignancy and two patients had no
      identifiable aetiology. Echocardiography-guided percutaneous pericardial puncture
      and pigtail catheter placement is safe and effective for initial treatment of
      patients with large pericardial effusion and cardiac tamponade and in most cases,
      initial assessment with clinical, serologic, and radiologic investigation and
      careful follow-up can reveal the aetiology. CONCLUSIONS: Although tuberculosis is
      rare in industrialized countries, in developing countries it remains one of the
      most important causes of large pericardial effusion and should be investigated
      and excluded in each patient.

PMID- 17536601
TI  - Procalcitonin in patients with acute coronary syndrome: correlation with high
      sensitive C-reactive protein, prognosis and severity of coronary artery disease.
AB  - OBJECTIVES: The aim of this study is to determine the relation of high-sensitive
      serum C-reactive protein (hsCRP) and procalcitonin with presence and severity of
      coronary artery disease and early prognosis in patients with acute coronary
      syndrome (ACS). METHODS AND RESULTS: Procalcitonin and hsCRP levels were measured
      at admission and after 48 hours in 50 patients (41 men, 9 women) with ACS. The
      patients were assigned to three groups according to their clinical diagnosis:
      unstable angina pectoris (UAP) (Braunwald III-B), non-ST-segment elevation
      myocardial infarction (NSTEMI) and ST-segment elevation myocardial infarction
      (STEMI). Incidences of adverse cardiac events were recorded in a 3-month follow
      up. Coronary angiography was performed to evaluate presence and severity of
      coronary artery disease. In the groups of STEMI, NSTEMI and UAP, procalcitonin (P
      = 0.01 3, P = 0.045 and P = 0.000 1, respectively) and hsCRP (P = 0.000 1, P =
      0.01 and P = 0.00 1, respectively) levels were significantly increased. No
      significant correlation was found between these markers and the presence and
      severity of coronary artery disease. There was no correlation between
      procalcitonin and hsCRP levels at admission and after 48 hours and primary end
      points after 3 months except in the group of UAP with revascularization
      procedure. In the group of UAP, hsCRP levels at 48 hours were found higher in the
      patients with a revascularization procedure (P = 0.04). CONCLUSIONS: In
      conclusion, levels of hsCRP and procalcitonin are increased in patients with ACS
      but failed to correlate with severity of coronary disease and early prognosis.

PMID- 17536602
TI  - Routine functional testing after percutaneous coronary intervention: results of
      the aggressive diagnosis of restenosis in high-risk patients (ADORE II) trial.
AB  - BACKGROUND: It is unclear whether routine or selective functional testing is
      optimal following percutaneous coronary intervention (PCI) in high-risk patients.
      OBJECTIVES: The aim of this trial was to compare exercise endurance, functional
      status, and quality of life (QOL) among high-risk patients randomized to either
      routine or selective functional testing following PCI. METHODS: We randomized 84
      patients to either routine or selective functional testing. Patients had one or
      more of the following: multivessel PCI, diabetes mellitus, left ventricular
      ejection fraction < 35%, and/or PCI of the proximal left anterior descending
      artery. Patients in the routine arm (n = 41) underwent maximum endurance exercise
      treadmill testing (ETT) with nuclear perfusion imaging at 1.5 and 6 months.
      Patients in the selective arm (n = 43) only underwent functional testing for a
      clinical indication. All patients underwent a maximum endurance ETT at 9 months.
      Exercise endurance, functional status, and QOL were assessed at 9 months.
      RESULTS: Most patients were middle-aged men (58 +/- 10 years old; 87% male) who
      underwent PCI with stenting (94%). Among routine functional testing patients,
      27.0% and 41.9% had a positive functional test at 1.5 and 6 months, respectively.
      Exercise endurance was improved in the routine vs. selective arm at 9 months
      (metabolic equivalents: 10.3 +/- 2.6 vs. 8.6 +/- 3.0, P = 0.013). There was no
      difference in improvement from baseline for the Duke Activity Status Index, the
      Seattle Angina Questionnaire, or the SF-36. Nine-month cumulative incidences of
      cardiac procedures and clinical events were not significantly different.
      CONCLUSIONS: Routine functional testing following PCI in high-risk patients may
      lead to improved exercise endurance but not improved QOL.

PMID- 17536603
TI  - Abnormal elastic properties of the aorta in the mitral valve prolapse syndrome.
AB  - BACKGROUND: Mitral valve prolapse (MVP) is the most common valvular heart disease
      representing a generalized disease of connective tissue in the primary form.
      Elastic properties of the aorta with primary MVP may be expected to be increased.
      We aimed to determine the aortic elasticity in the primary form of MVP. METHODS
      AND RESULTS: Twenty male patients with a primary form of MVP not having any sign
      of Marfan syndrome and joint hyperlaxity syndrome and twenty healthy individuals
      were included in the study. Aortic strain, aortic distensibility index and aortic
      stiffness index were calculated by using aortic diameters obtained by
      echocardiography and blood pressures measured by sphygmomanometer. When comparing
      the MVP group and the control group it was found that the aortic stiffness index
      was increased (P < 0.05) whereas the aortic distensibility and strain index were
      decreased (P < 0.05) in the MVP group. There was no significant difference
      between the characteristics of the groups (P > 0.05). CONCLUSION: We concluded
      that the elastic properties of the aorta were decreased in the primary form of
      MVP, unexpectedly.Therefore, results of decreased aortic elasticity should also
      be followed up in patients with MVP.

PMID- 17536604
TI  - Angiotensin-converting enzyme inhibitor improves force and Ca2 +--frequency
      relationships in myocytes from rats with heart failure.
AB  - OBJECTIVES: The objectives were to study the effects of an ACE inhibitor on the
      force-frequency relationship (FFR) and its possible mechanism in isolated failing
      myocytes. METHODS AND RESULTS: Male Wistar rats were randomized into a heart
      failure group treated with perindopril (CHF-T, 3 mg.kg(-1)d-1), a heart failure
      group without treatment (CHF-C) and a sham-operated group (PS). Heart failure was
      induced by constriction of the abdominal aorta. All groups were further followed
      up for 12 weeks. Left ventricular myocytes were isolated. Cell-shortening
      fraction (FS) and intracellular calcium transients were measured at different
      frequency field stimulations. A negative force-frequency relationship (FFR) was
      found in the CHF-C group compared with the positive-negative biphasic FFR in the
      PS group, and a flat FFR in the CHF-T group. Intracellular Ca2+ frequency
      relationships (CaFRs) were positive-negative biphasic in both the PS and CHF-T
      groups, whereas a negative CaFR was found in the CHF-C group. Regardless of the
      stimulation frequency, FS significantly correlated with [Ca2+]imax in the PS or
      CHF-C groups. Compared to the PS group, protein levels of SERCA2 significantly
      decreased and NCX1 increased in the CHF-C group. In the CHF-T group, these
      changes were reduced. CONCLUSION: The ACE inhibitor could improve the impaired
      FFR of isolated failing myocytes. This effect was possibly mediated via
      ameliorating the disturbance of CaFR.

PMID- 17536605
TI  - Catheter ablation of haemodynamically unstable or non-sustained ventricular
      tachycardia.
AB  - BACKGROUND: Ventricular tachycardia (VT) may be haemodynamically unstable or non
      sustained, interfering with detailed activation mapping. Non-contact mapping
      permits beat-by-beat analysis of VT, projected upon a 3-dimensional reconstructed
      geometry of the cardiac chamber. Objective - The aim of the present study is to
      determine the utility of non-contact endocardial mapping to guide ablation of
      haemodynamically unstable VT or non-sustained VT. METHODS AND RESULTS: Eighteen
      VTs in 17 patients were induced (cycle length 336 +/- 58 ms) and mapped. Three
      patients were mapped during premature ventricular complexes (PVCs) because
      sustained VT could not be induced. Analysis of the archived non-contact
      activation maps was performed to identify the exit point and/or the diastolic
      pathway of theVT reentry circuit. The endocardial exit points (10 +/- 16 ms
      before QRS) were defined in 17/18 VTs (94%). A diastolic pathway was identified
      in 5/6 ischaemic VTs. The earliest activation sites were identified in all 3
      patients with PVCs. Radiofrequency current was applied around the exit point or
      to create a line of block across the diastolic pathway. Catheter ablation was
      performed in 17/18 VTs, including 3 patients mapped using only PVCs. Ablation was
      successful in 16/18 VTs (89%) and in 1 5/17 patients (82%). Catheter ablation was
      not performed in one patient (peri-hisian VT) and was unsuccessful in one patient
      (mapped during PVCs). CONCLUSIONS: Non-contact endocardial mapping is useful to
      guide radiofrequency catheter ablation of untolerated or non-sustained VTs.

PMID- 17536606
TI  - Brain natriuretic peptide correlates with troponin T in patients with renal
      failure.
AB  - OBJECTIVES: In patients with chronic renal failure, the main cause of mortality
      is cardiovascular disease. Cardiac troponin T (cTnT) and brain natriuretic
      peptide (BNP) are found to be related with decreased survival in both the normal
      population and in patients with chronic renal failure in different studies. Our
      aim is to investigate the relationship between cTnT and BNP in patients with
      chronic renal failure. METHODS AND RESULTS: 58 chronic haemodialysis patients
      were enrolled prospectively for the study. Blood samples for measurement of cTnT
      and BNP were collected after the haemodialysis. The patients are divided into 3
      groups according to cTnT measurements. Group I included the patients with cTnT <
      0.05 ng/ml, Group II included the patients with cTnT between 0.05 and 0.1 ng/ml
      and group III included the patients with cTnT > 0. 1 ng/ml. We performed
      echocardiography in all patients to measure the left ventricular ejection
      fraction and thickness of septum and posterior wall. When BNP levels were
      compared among the 3 groups, we found that the BNP level was lowest in group I
      and highest in group III (165.13 +/- 125.44 pg/dl; 236.0 +/- 107.83 pg/dl; 280.71
      +/- 153.25 pg/dl, respectively) (P = 0.01).The difference in BNP levels among
      groups was statistically significant and independent from left ventricular
      hypertrophy, left ventricular ejection fraction and volume overload in multiple
      regression analysis. We also searched the relationship between plasma cTnT and
      BNP levels and found a positive correlation (r = 0.3; P = 0.023). CONCLUSION:
      cTnT and BNP levels were related to each other in patients with chronic renal
      failure.These parameters can help to identify the patients with a high risk for
      cardiovascular diseases.

PMID- 17536607
TI  - Osteopontin levels are associated with cholesterol synthesis markers in mildly
      hypercholesterolaemic patients.
AB  - OBJECTIVE: Atherosclerotic lesions are characterized by an accumulation of
      inflammatory cells and lipids. Osteopontin (OPN) is a cell-binding
      phosphoprotein, and it seems to promote the development of atherosclerosis. The
      purpose of our study was to find out whether plasma levels of OPN are associated
      with cholesterol metabolites in plasma or tissues. METHODS AND RESULTS: Forty
      three normal or mildly hypercholesterolaemic subjects, aged 31 to 69, were
      studied. The plasma level of OPN correlated negatively with muscle lathosterol (r
      = -0.52, P < 0.0001) and with the muscle lathosterol to muscle cholesterol ratio
      (r = -0.48, P = 0.001). Lathosterol concentrations in muscle (P = 0.003) and in
      relation to cholesterol (P = 0.005) were also significantly different among the
      OPN tertiles. OPN correlated negatively and significantly with muscle lathosterol
      in men (r = -0.58, P = 0.001, n = 29) but not in women (r = -0.21, P = 0.48, n =
      14). Correspondingly, it also correlated negatively and significantly with the
      muscle lathosterol to muscle cholesterol ratio (r = -0.60, P = 0.001) in men but
      not in women (r = -0.13, P = 0.65). Plasma levels of OPN had a non-significant
      inverse correlation with plasma lathosterol and the plasma lathosterol to plasma
      cholesterol ratio. Plasma OPN concentrations were not related to plant sterols,
      cholesterol and 27-hydroxycholesterol. CONCLUSIONS: Tissue markers of cholesterol
      synthesis were related to plasma OPN, particularly in men. This suggests that
      there is interplay between OPN and cholesterol metabolism in human cells.

PMID- 17536608
TI  - The role of elective coronary surgery early after acute myocardial infarction in
      the era of primary percutaneous coronary intervention.
AB  - AIMS: There is a group of patients with acute myocardial infarction (AMI), who,
      according to results of emergency coronary angiography and regardless of
      performed or not performed primary percutaneous coronary intervention (PCI), are
      qualified for elective coronary artery bypass grafting (CABG). The authors have
      not found a publication that focuses on this problem. They tried to determine the
      base-line characteristic of this subgroup as well as appreciate its operative
      surgical risk. METHODS AND RESULTS: Emergency coronary angiography - followed by
      primary PCI when appropriate - was performed in 1867 consecutive patients with
      AMI. Of all these patients, 85 (4.6%) were qualified at the further stage of
      treatment for elective CABG. Compared with patients requiring only PCI (n =
      1771), those undergoing elective CABG were the same age (61.9 +/- 9.4 vs. 61.8 +/
      12.8 years) and gender, but more frequently suffered from hypertension, diabetes
      mellitus, lipid disorders and multi-vessel disease. The majority of CABG patients
      (56.5%) belonged to the medium risk group according to the calculated EuroSCORE
      ratio. The mean value of the logistic EuroSCORE was 5.26 +/- 8.07. CONCLUSIONS:
      The elective CABG in patients early after AMI, who underwent emergency coronary
      angiography to perform primary PCI, is an integral part of treatment. However,
      this procedure usually regards only few patients. Numerous risk factors of
      coronary artery disease are present in those patients, who belong, however, to
      the medium operative risk group.

PMID- 17536609
TI  - A new era for oral anticoagulation? Old and new anticoagulant drugs.
AB  - The expanding demand for long-term antithrombotic therapy and the major
      limitations of the vitamin-K antagonists, namely their narrow therapeutic range,
      numerous drug interactions and need for laboratory monitoring, have stimulated
      the development of new antithrombotic agents. Direct thrombin inhibitors and
      factor Xa inhibitors are the new classes of orally available anticoagulants that
      are most advanced in development. Large clinical trials evaluate several
      compounds both in the primary and secondary prevention of venous thromboembolism
      and in the prevention of cardioembolism in patients with atrial fibrillation.

PMID- 17536610
TI  - An alternative method of prosthetic mitral valve implantation in the presence of
      extensive calcification.
AB  - Annular calcifications carry some technical difficulties for success in
      conventional valve surgery. In this paper we present an easy alternative mitral
      valve replacement method applied for a patient with a heavily calcified mitral
      annulus. Excision of both leaflets and partial resection of the annular
      calcification with an ultrasonic dissector allowed the intra-atrial insertion of
      a 33-mm Omnicarbon monoleaflet prosthetic valve through a smaller opening of the
      left posterior atrium. The technical difficulties in inserting a prosthetic valve
      in a patient with a heavily calcified mitral annulus are discussed.

PMID- 17536611
TI  - Heart failure with mitral valve regurgitation due to primary hyperoxaluria type
      1: case report with review of the literature.
AB  - Primary hyperoxaluria type I (PH I) is a rare recessive autosomal disorder
      characterized by systemic calcium oxalate depositions, that results in renal
      failure and systemic oxalosis. We report a 38-year-old male with cardiac
      oxalosis, a severe complication of PHI, presenting with an infiltrative
      cardiomyopathy, secondary heart failure and severe mitral regurgitation,
      necessitating surgical repair to allow combined liver-kidney transplantation. We
      discuss pathogenesis, diagnostics and therapy of this clinical entity by
      reviewing literature.

PMID- 17536612
TI  - Surgical treatment of Wolff-Parkinson-White syndrome: a timeless procedure?
AB  - Catheter-induced radiofrequency (RF) ablation has become the initial non
      pharmacological treatment option for Wolff-Parkinson-White (WPW) syndrome. In
      this report, we present the successful surgical treatment of WPW syndrome in two
      patients in whom percutaneous ablation of the accessory pathway was not
      successful.

PMID- 17536613
TI  - Worsening heart failure following cardiac resynchronization therapy: an
      electrocardiographic diagnosis.
AB  - The advent of biventricular devices has added new complexity to the evaluation of
      pacemaker function and follow-up. Consequently one must acknowledge the various
      circumstances that can disrupt ventricular resynchronization and provoke
      haemodynamic deterioration. In this paper we report upon haemodynamic
      deterioration following resynchronization therapy because of an erroneous
      connection of an epicardial right ventricular (RV) outflow tract lead to the left
      ventricular (LV) channel of the device. How ECG and echocardiography can guide
      the diagnosis and help in prematurely detecting abnormal pacing or loss of LV
      capture is discussed in detail below.

PMID- 17536614
TI  - Hydrochlorothiazide-associated noncardiogenic pulmonary oedema and shock: a case
      report and review of the literature.
AB  - Diuretics, especially thiazide-type diuretics, are widely used in the treatment
      of essential hypertension. The most frequent adverse reactions are hypotension,
      photosensitivity, hypokalaemia, anorexia and epigastric distress. Life
      threatening adverse reactions are rare. We report a case of pulmonary oedema
      associated with low left ventricular filling pressures and hypotension, occurring
      in a patient shortly after ingestion of 12.5 mg of hydrochlorothiazide (HCTZ). By
      reviewing the literature (Medline search) 49 similar cases were found. We
      compared the findings of all these patients in an attempt to reveal the
      underlying mechanism of this non-cardiogenic pulmonary oedema and shock. We
      believe that an allergic type III reaction is most likely the underlying
      mechanism of this adverse drug reaction to HCTZ. It is important to recognize the
      causality of the symptoms of this rare but life-threatening side effect of
      thiazide-type diuretics, in order to stop the drug intake immediately and to
      prevent any unthoughtful reinitiation of this treatment.

PMID- 17536615
TI  - Food or fluid restriction in common laboratory animals: balancing welfare
      considerations with scientific inquiry.
AB  - Deprivation or restricted access to either food or fluids is a common research
      procedure in laboratory animals. The purpose of the present review is to present
      and summarize some of the important physiologic effects of such procedures and to
      assess their effect on the well-being of the animal. This assessment is presented
      within a context of the typical research objectives of such procedures. Specific
      suggestions are made that are intended to strike a balance between meeting these
      research objectives and ensuring the physiologic and behavioral welfare of the
      animals under study. Most of the information presented is specifically related to
      rats and mice but, with appropriate adjustments, the principles likely will
      generalize to other laboratory species. I present evidence that after 12 to 24 h
      without access, animals efficiently reduce further fluid or energy losses by a
      combination of behavioral and physiologic adjustments. These adjustments likely
      minimize the additional physiologic or psychologic stress of deprivation. Animals
      have endogenous nycthemeral rhythms that make them particularly adaptable to once
      daily occurrences, such as food or water access. Longer periods of acute
      deprivation or chronic restriction are acceptable procedures, but only with
      suitable monitoring protocols, such as routine weighing and target weights. In
      the case of chronic food restriction, the use of species-, age-, and strain
      specific target growth rates is more appropriate than using a fraction of age
      matched free-fed animal weights as a target.

PMID- 17536616
TI  - Aspects of morphine chemistry important to persons working with cold-blooded
      animals, especially fish.
AB  - The relative amounts of the different forms of morphine, and many other
      pharmacologic agents, depend on temperature and pH. Some forms are more
      efficacious because they are uncharged and can penetrate lipid membranes more
      easily than the charged forms. Persons who administer pharmacologic agents to
      ectotherms (that is, cold-blooded animals) should consider the effect of
      temperature on the relative amounts of the different forms of drugs. For example,
      the fraction of morphine present in the uncharged form is twice as high in a fish
      or frog at 5 degrees C as in a mammal at 37 degrees C. Moreover, because the pH
      of blood, plasma, and tissues of ectotherms is higher when they are held at lower
      temperatures, the combined effect of temperature and pH on the speciation of
      pharmacologic agents also should be considered. In addition, the total solubility
      of morphine and other pharmacologic agents depends on temperature and pH. The
      purpose of this overview is to describe how temperature and pH influence the
      solubility and speciation of morphine.

PMID- 17536617
TI  - The effects of analgesic supplements on neural activity in the main olfactory
      bulb of the mouse.
AB  - We evaluated ketoprofen, a nonsteroidal anti-inflammatory drug (NSAID), as an
      antinociceptive supplement to chloral hydrate anesthesia in mouse. Effects of
      ketoprofen on main olfactory bulb (MOB) neuronal spontaneous activity were
      investigated using extracellular recordings in mouse in vivo. These effects were
      compared with those of another nociceptive supplement, the mu-opioid agonist
      buprenorphine. Ketoprofen (100 or 200 mg/kg) did not significantly alter MOB
      single-unit spontaneous rates in either ICR or C57BL/6J mice. In contrast,
      buprenorphine, at doses of 0.02, 0.05, and 0.20 mg/kg, inhibited MOB neuronal
      spontaneous rates by 19%, 49%, and 57%, respectively. Neither drug altered the
      temporal patterning of single-unit spike trains, as measured by the interspike
      interval (ISI) coefficient of variation (CV). We also investigated the ability of
      ketoprofen and buprenorphine to induce antinociception in the anesthetized mouse.
      The electroencephalogram (EEG) was used to measure the anesthetic plane. Both
      ketoprofen and buprenorphine altered the EEG trace and ketoprofen altered the
      power spectrum in a manner consistent with deepening anesthesia. Lastly, when
      applied at the time of anesthesia induction, ketoprofen decreased the amount of
      chloral hydrate necessary to maintain a defined anesthetic plane during the rest
      of the experiment. These results suggest that ketoprofen induces antinociception
      under chloral hydrate anesthesia without significantly inhibiting spontaneous
      activity of MOB neurons. Ketoprofen is therefore suitable as an antinociceptive
      supplement to chloral hydrate anesthesia during in vivo electrophysiologic
      recordings of the mouse MOB.

PMID- 17536618
TI  - Ex vivo optical coherence tomography and laser-induced fluorescence spectroscopy
      imaging of murine gastrointestinal tract.
AB  - Optical coherence tomography (OCT) and laser-induced fluorescence (LIF)
      spectroscopy each have clinical potential in identifying human gastrointestinal
      (GI) pathologies, yet their diagnostic capability in mouse models is unknown. In
      this study, we combined the 2 modalities to survey the GI tract of a variety of
      mouse strains and ages and to sample dysplasias and inflammatory bowel disease
      (IBD) of the intestines. Segments (length, 2.5 cm) of duodenum and lower colon
      and the entire esophagus were imaged ex-vivo with combined OCT and LIE We
      evaluated 30 normal mice (A/J and 10- and 21-wk-old and retired breeder C57BL/6J)
      and 10 mice each of 2 strains modeling colon cancer and IBD (Apc(Min) and IL2
      deficient mice, respectively). Histology was used to classify tissue regions as
      normal, Peyer patch, dysplasia, adenoma, or IBD. Features in corresponding OCT
      images were analyzed. Spectra from each category were averaged and compared via
      Student t tests. OCT provided structural information that led to identification
      of the imaging characteristics of healthy mouse GI. With histology as the 'gold
      standard,' we developed preliminary image criteria for early disease in the form
      of adenomas, dysplasias, and IBD. LIF characterized the endogenous fluorescence
      of mouse GI tract, with spectral features corresponding to collagen, NADH, and
      hemoglobin. In the IBD sample, LIF emission spectra displayed potentially
      diagnostic peaks at 635 and 670 nm, which we attributed to increased porphyrin
      production by bacteria associated with IBD. OCT and LIF appear to be useful and
      complementary modalities for ex vivo imaging of mouse GI tissues.

PMID- 17536619
TI  - Effects of leukotriene inhibition on pulmonary morphology in rat pup lungs
      exposed to hyperoxia.
AB  - Assisted ventilation is necessary for treating preterm infants with respiratory
      distress syndrome. Unfortunately, high and prolonged concentrations of oxygen
      associated with assisted ventilation often lead to pulmonary changes, such as
      hemorrhage and inflammation. The resulting chronic pulmonary condition is known
      as bronchopulmonary dysplasia. Pulmonary changes characteristic of this syndrome
      can be produced in rat pups exposed to high oxygen levels. We exposed 21-d-old
      rats to room air or continuous 95% oxygen for 7 d and then allocated them into 6
      groups to evaluate whether treatment with zileuton and zafirlukast, 2 agents
      which decrease the effects of leukotrienes, lessened the pulmonary effects of
      short-term hyperoxia. After 7 d, lung tissue was collected for light and electron
      microscopy. Pulmonary changes including edema, hemorrhage, alveolar macrophage
      influx, and Type II pneumocyte proliferation were graded on a numerical scoring
      system. Compared with controls exposed to hyperoxia [corrected] and saline, rats
      exposed to hyperoxia and treated with zileuton had significantly reduced levels
      of alveolar macrophage influx and Type II pneumocyte proliferation, but those
      exposed to hyperoxia [corrected] and treated with zafirlukast showed no
      significant reduction in any pulmonary changes. This study helps define pulmonary
      changes induced secondary to hyperoxia in rat pups and presents new information
      on the mechanisms of leukotriene inhibition in decreasing the severity of
      hyperoxic lung injury.

PMID- 17536620
TI  - Breeding colony refinement through phenotypic and genotypic characterization of
      the SPRD-Pkdr1/Rrrc rat model of polycystic kidney disease.
AB  - The SPRD-Pkdr1 rat model is widely used for the study of human autosomal dominant
      polycystic kidney disease. This rat model carries the Cy allele of the Pkdr1
      gene, which results in polycystic kidney disease. Because the Cy allele is lethal
      in the homozygous state at weanling age, the breeding colony must be maintained
      in the heterozygous state. A random breeding scheme in which production of
      homozygous pups with enlarged kidneys indicates heterozygous breeders is commonly
      used. This study was performed to determine whether biochemical markers (blood
      urea nitrogen [BUN] or creatinine), ultrasonography, or genetic analysis could be
      used to select breeding animals in the SPRD-Pkdr1/Rrrc colony and thus replace
      the random breeding scheme with a more efficient selective breeding scheme. BUN
      was predictive of the Cy allele in 8- to 9-wk-old male but not female rats.
      Ultrasonography identified animals with polycystic kidney disease in both sexes
      by 9 wk of age. Microsatellite marker polymorphism analysis could not be used to
      determine carrier status for the Cy allele, but restriction fragment length
      polymorphism analysis appropriately detected the Cy allele in 100% of the animals
      examined. In conclusion, multiple methods can be used for detecting the Cy
      allele, making possible a selective breeding scheme that markedly reduces the
      necessary number of breeder animals and eliminates the euthanasia of offspring
      needed with a random test-mating scheme.

PMID- 17536621
TI  - Brief small intestinal ischemia lessens renal ischemia-reperfusion injury in
      rats.
AB  - Ischemic preconditioning (IPC) not only reduces local tissue injury caused by
      subsequent ischemia-reperfusion (IR) but may also have a beneficial effect on IR
      injury of tissues remote from those undergoing preconditioning. In this study, we
      investigated the effect of small intestinal IPC on renal IR injury in rats. Renal
      IR injury was induced by a 45-min renal artery occlusion and reperfusion for 2 or
      24 h in rats with a previous contralateral nephrectomy, and ischemic
      preconditioning was induced by 3 cycles of 8-min ischemia and 5-min reperfusion
      of the small intestine. We then measured the concentrations of plasma creatinine
      (Cr) and blood urine nitrogen (BUN) and the level of malondialdehyde (MDA) and
      activities of superoxide dismutase (SOD) and catalase (CAT) in the renal cortex.
      Renal histopathology also was evaluated. Pretreatment with intestinal ischemic
      preconditioning significantly alleviated renal IR injury, as shown by decreases
      in the levels of Cr, BUN, and MDA, decreased renal morphologic change, and
      improved preservation of SOD and CAT activities. These results suggest that
      remote ischemic preconditioning of the small intestine protects against renal IR
      injury by inhibition of lipid peroxidation and preservation of antioxidant enzyme
      activities.

PMID- 17536622
TI  - Comparison of various anthelmintic therapies for the treatment of Trypanoxyuris
      microon infection in owl monkeys (Aotus nancymae).
AB  - Trypanoxyuris microon is a pinworm that infects New World nonhuman primates,
      including Aotus nancymae. Although it typically is clinically insignificant,
      infection may serve as a significant variable during experimental data analysis.
      In this study we sought to determine the most effective anthelmintic therapy for
      eradication of T. microon infection in A. nancymae. Animals confirmed to be
      infected with T. microon by perianal tape test were treated twice (on days 0 and
      14) with pyrantel pamoate, ivermectin, or thiabendazole and evaluated for eggs by
      daily perianal tape test throughout the entire 28-d period. Successful clearance
      of eggs was defined as 5 consecutive negative perianal tape tests. Pyrantel
      pamoate and ivermectin were significantly more effective at egg clearance than
      were thiabendazole and no treatment. Overall, 100% of the pyrantel pamoate and
      ivermectin treatment groups were cleared of infection after 2 treatments, whereas
      only 60% of the thiabendazole group became negative for pinworm eggs. In
      addition, the time after treatment until clearance was 1 to 2 d for pyrantel
      pamoate, 2 to 4 d for thiabendazole, and 4 to 6.5 d for ivermectin. These results
      indicate that pyrantel pamoate was the most effective and rapidly acting
      anthelmintic for the treatment of adult T. microon infection, with ivermectin as
      a suitable alternative. However because of the potential for continued
      development of immature stages or reinfection, anthelmintic doses should be
      repeated after 1 to 2 wk, in combination with effective environmental sanitation.

PMID- 17536623
TI  - Spontaneous exocrine pancreas hypoplasia in specific pathogen-free C3HeB/FeJ and
      101/H mouse pups causes steatorrhea and runting.
AB  - Under specific pathogen-free conditions, 1.3% to 1.8% of litters born in our
      inbred 101/H and C3HeB/FeJ mouse colonies had pups with steatorrhea and runting.
      Clinically affected male and female pups were first identified when they were
      from 14 to 25 d old. Unaffected littermates were healthy and were weaned
      successfully. Postmortem findings in 8 clinically affected mice included a small,
      poorly differentiated exocrine pancreas comprising cytokeratin-negative duct-like
      structures but lacking recognizable acinar cells with their normal
      carboxypeptidase B-positive zymogen granules. Endocrine pancreas islets were
      unremarkable and contained insulin-positive beta cells and glucagon-positive
      alpha cells. There was mild inflammation of the hindgut but no evidence of
      intestinal pathogens or marked inflammation or necrosis of pancreas, either alone
      or as part of a multisystemic inflammatory condition. Sera from pups in 4
      affected litters did not contain antibodies to reovirus 3, mouse coronavirus,
      rotavirus, or mouse adenovirus 2. Furthermore, 4 sets of parental mice and
      sentinel mice from the facility were negative for 13 viruses, bacteria, and
      parasites. C3HeB/FeJ and 101/H inbred strains may be genetically predisposed
      because the steatorrhea and runting was absent in 13 other mouse strains and
      subspecies bred in the specific pathogen-free facility. This condition resembles
      exocrine pancreas hypoplasia, but the inheritance is complex. A wider implication
      is that runting coupled with steatorrhea are phenotypic criteria to suspect
      pancreatic disease that could be used in the context of a mouse N-ethyl-N
      nitrosourea-mutagenesis program to identify potential mutants with defects in
      pancreas development.

PMID- 17536625
TI  - New weight limit for instrument sets.

PMID- 17536624
TI  - Should physicians be expected to disclose conflicts of interest?

PMID- 17536626
TI  - Surgeon leads effort for safer surgery. Interview by Pat Patterson.

PMID- 17536627
TI  - Kids at highest risk of periop med errors.

PMID- 17536628
TI  - Can OR inventory be like a grocery store?

PMID- 17536629
TI  - A quest for a perfect OR inventory.

PMID- 17536630
TI  - Data on implant costs wins MD support.

PMID- 17536631
TI  - Seven steps to a stronger supply chain.

PMID- 17536632
TI  - Is your ASC leaving money on the table?

PMID- 17536633
TI  - The introduction of a chest pain nurse and fast-track troponin service reduces
      the length of stay of patients presenting with chest pain.
AB  - BACKGROUND: Troponin I (TnI) measurement is important in decision making and
      management of patients who present with chest pain. Undetectable levels of TnI in
      these patients are associated with a low risk of death or myocardial infarction
      at 30 days, and may allow early discharge from hospital. METHODS: An audit was
      performed tracking patients who presented with chest pain and had a TnI blood
      test requested. Routine clinical service was audited for three months. A "fast
      track" troponin service and chest pain specialist nurse was then introduced to
      assist in the management of patients. This was continued for three months to
      assess the impact on length of stay. RESULTS: 446 patients were admitted during
      the first three month period and 511 patients admitted during the second
      monitoring period when the new measures were introduced. The time from chest pain
      onset until the TnI blood test was taken reduced from 23.0 hours to 20.3 hours.
      The percentage of patients admitted to hospital wards from the Acute Medical
      Receiving Unit (AMRU) fell from 62% to 53% (p < 0.001). The new measures resulted
      in a reduction in admission time from 73.1 hours to 51.0 hours. CONCLUSION: A
      fast-track troponin and specialist nurse achieved a reduction of nearly 24 hours
      in length of stay in patients presenting with chest pain. This would result in a
      saving of approximately 2000 bed-days per annum, releasing 5-6 acute beds per
      day.

PMID- 17536634
TI  - Stop the brain drain: ways to improve recruitment and retention to Scottish
      consultant posts.
AB  - BACKGROUND AND AIMS: NHS Scotland loses approximately one-third of Specialist
      Registrars (SpRs) it trains to consultant posts elsewhere. This has considerable
      resource and service implications and is the cause of intense political
      frustration. This study sought to gather data about the career intentions of SpRs
      and to discover what factors influence their career decisions. METHODS: All SpRs
      in Scotland due to gain their Certificate of Completion of Specialist Training
      (CCST) between April 2005 and March 2006 were approached to take part in an
      interview about their career aspirations. Interviews, using a structured
      interview schedule, took place in spring 2005. RESULTS: 198 SpRs were interviewed
      -75% of the target population. Almost three-quarters would prefer to stay in
      Scotland if possible, but when asked to realistically predict where they would
      take up a consultant post, this proportion had dropped to 64%. Perceived barriers
      to working in Scotland included the large number of District General Hospital
      (DGH) posts (often with onerous on-call rotas). A further problem concerned poor
      information flow between NHS Boards and trainees, with trainees being lost to
      Scotland who might have stayed if a job had been advertised in time. CONCLUSIONS:
      The majority of SpRs would prefer to stay in Scotland for their consultant
      career. There is a need to improve information flow between NHS Boards and
      trainees. NHS Boards need to know more about the career intentions of trainees
      and training committees and trainees need to be informed as to when and where
      posts will be advertised. Posts in DGHs might be made more appealing by having
      some sessions in larger teaching hospitals (although split-site working is not
      always popular). Flexibility and part-time options need to be promoted.

PMID- 17536635
TI  - The use of the artificial urinary sphincter in the West of Scotland: a single
      centre 10-year experience.
AB  - BACKGROUND: The artificial urinary sphincter (AUS) has been used successfully to
      treat sphincter weakness incontinence in males over the past 30 years.
      Postoperative complications are well-recognised, but patient satisfaction remains
      high. METHODS: We performed a retrospective single centre study of all patients
      who had an artificial urinary sphincter inserted over a 10-year period. We
      assessed patient satisfaction and continence post operatively as well as
      complication rate and need for revision or replacement surgery. RESULTS: Thirty
      eight male patients (mean age 57 years) and 1 female patient had an AMS 800
      (American Medical systems) AUS inserted between 1995 and 2005. Five (13%)
      patients have required replacement surgery to date. Male patients were divided
      into two groups according to the aetiology of their incontinence: neuropathic (n
      = 11) and non-neuropathic (n = 27). Social continence was achieved in all
      patients. Three (11%) non-neuropathic patients developed complications. Revision
      surgery was undertaken in 4 (15%) of non-neuropathic patients and in 1 (9%)
      neuropathic patient. The mean lifespan of the AUS in patients who required
      further surgery is 6.6 years. CONCLUSION: For patients with severe sphincter
      weakness incontinence the AMS 800 AUS is a safe and reliable solution. Our
      results are comparable with previous published studies of larger patient numbers
      from dedicated reconstructive units.

PMID- 17536636
TI  - Vasectomy reversal: is the microscope really essential?
AB  - OBJECTIVE: To evaluate the outcomes of bilateral vasectomy reversal procedure in
      relation to the macroscopic technique, surgical time and duration of obstructive
      interval. MATERIALS AND METHODS: We performed a retrospective study over a twelve
      year period using a macroscopic technique. All cases of vasectomy reversal were
      consecutive and performed by the same surgeon. The procedure was performed using
      a single layer, spatulate end to end anastomosis technique using 6 x 6-0 prolene.
      No loupe magnification was used. RESULTS: The median age of the men was 42 years
      (range 30-56). The median obstructive interval in years was 8.5 years (range 2
      23). The procedure was a day case and the median surgical time under general
      anaesthetic was 75 minutes (range 45-90). None of the patients required hospital
      admission following discharge. 63 of the 70 patients had positive patency test
      postoperatively (90%). The sperm count was more than twenty million/ml. The
      pregnancy rate was 54% and the miscarriage rate was 7.1%. CONCLUSION: The
      outcomes of macroscopic vasectomy reversal performed by an experienced surgeon
      can have a high success rate using the macroscopic single layer spatulate end to
      end anastomosis technique. This technique is easy to learn compared to the
      learning curve involved in microsurgery and is an effective means of "re-
      establishing" fertility in vasectomised men.

PMID- 17536637
TI  - Audit of literacy of medical patients in north Glasgow.
AB  - AIMS: We aimed to assess the scale of the problem of illiteracy among our
      hospital's general medical in-patients and investigate any influence on literacy
      from gender, age, socioeconomic status, disease process and number of prescribed
      medications. METHODS: We employed a shortened version of the previously validated
      Rapid Estimate of Adult Literacy in Medicine (REALM) tool with medical in
      patients at Glasgow Royal Infirmary. We also recorded gender, date of birth and
      clinical problem. Socioeconomic status was estimated from the patient's postcode
      using the Scottish Index of Multiple Deprivation (SIMD). RESULTS: 60 patients
      were invited to participate, however six (10%) declined. We therefore gathered
      data for 54 patients (54% male) with a mean age of 67 years. The female group had
      a significantly higher mean age of 73 years versus 62 years in men. The mean SIMD
      quintile was 3.5 (1 least deprived, 5 most deprived) and the mean number of
      medications was 7.55% of our patients had a mean score of < 60 which represents
      low health literacy. There were no significant differences in literacy between
      men (median score 59) and women (median score 60). Reading ability was not found
      to be associated with socioeconomic group, diseased body system or number of
      medications on the drug chart (data not shown). CONCLUSIONS: Low level health
      literacy is prevalent. Affected individuals may have difficulty understanding
      patient-orientated health literature, medication instructions, clinic appointment
      cards and hospital signage.

PMID- 17536638
TI  - Clinical audit: optimal positioning of endotracheal tubes in neonates.
AB  - BACKGROUND: The malposition of endotracheal tubes (ETTs) can be associated with
      endo-bronchial intubation or accidental extubation. A variety of methods have
      been reported for predicting insertional length (IL) including weight, nasal
      tragus length (NTL) and sternal length (STL) measurements. In our unit no
      consistent predictor method was being used. AIM: To audit the proportion of
      endotracheal tubes that required a significant position change after oral
      intubation. Our standard set was that the endotracheal tube should be in a
      satisfactory position in > 80% of cases. If not met, practice would then be re
      audited after a consistent predictor method had been implemented. METHODS: Data
      regarding changes in endotracheal tube position were collected. Significant
      position changes were defined as adjustments > 0.5 cm. RESULTS: Twenty two babies
      were included in the initial audit, and only 73% of endotracheal tubes had a
      satisfactory position. Thirty six babies were included in the re-audit and when
      the nasal-tragus length predictor was used, 94% of endotracheal tubes had a
      satisfactory position, meeting the standard. CONCLUSION: The nasal-tragus length
      predictor improved the accuracy of endotracheal tube positioning after oral
      intubation. It is a simple, fast, reproducible method and can be used in everyday
      practice to help avoid significant endotracheal tube malposition.

PMID- 17536639
TI  - An audit of the value of pre-operative electrocardiograms before surgery (general
      anaesthetic) in a day surgery unit.
AB  - BACKGROUND: As the population presenting for day-case surgery and anaesthesia
      increases, so does the challenge of adequate pre-operative assessment. The
      resting 12-lead electrocardiogram (ECG) is relatively insensitive and frequently
      normal even in the presence of severe coronary artery disease but it is quick,
      easy to perform and frequently requested, thus its value in day-case surgery
      remains unproven. AIMS: To assess whether patients at Day Surgery Unit, Gartnavel
      General Hospital who fit the ECG criteria get an immediate ECG and also to review
      whether abnormal ECG results leads to any change in the patient's management.
      METHODS: A prospective audit was performed on all patients coming in for
      noncardiac day-case surgery over a 3-week period between February 2006 and March
      2006. Patient notes were reviewed before their surgery. RESULTS: 60 patients
      presenting for day-case surgery over this period should have had an ECG done but
      only 24 were referred. A significant abnormality was noted in 12.5% of ECGs. None
      of these patients had their surgery postponed or management changed. No adverse
      events occurred in patients proceeding to surgery and there were no cases of peri
      operative cardiovascular complications or admissions to hospital. CONCLUSION: The
      finding of ECG abnormalities did not prevent the patient proceeding directly to
      anaesthesia and surgery. Furthermore, they did not predict intra-operative,
      postoperative complications or hospital admission following the procedure. The
      ECG is of limited value in the risk stratification of patients selected for day
      case surgery.

PMID- 17536640
TI  - Update on sarcomas of bone and soft tissue.

PMID- 17536641
TI  - What's new in COPD?

PMID- 17536642
TI  - Sir John Charnley (1911-1982): inspiration to future generations of orthopaedic
      surgeons.
AB  - For young doctors embarking on a career in medicine, the decision on which path
      to take is often influenced by their experiences as an undergraduate student and,
      in particular, by those doctors and teachers who have stimulated and encouraged
      them. Likewise, inspiration can be derived from studying the life and work of
      eminent practitioners of the past. A final year elective module provided me with
      the opportunity to undertake a detailed critique of an aspect of the history of
      medicine of my choosing, which enabled me to investigate the history of hip
      replacement. This opened my eyes to the prodigious contribution of Sir John
      Charnley in the field of orthopaedics. His commitment to the practice and
      advancement of medical science is indeed an inspiration. This account of John
      Charnley's work is a testimony to the lifetime achievements of one man, whose
      hard work and dedication have brought enormous benefit to generations of patients
      the world over.

PMID- 17536643
TI  - Incorporating research evidence into clinical practice decisions.

PMID- 17536644
TI  - The physiotherapy management of patients undergoing thoracic surgery: a survey of
      current practice in Australia and New Zealand.
AB  - BACKGROUND AND PURPOSE: Physiotherapy is considered an essential component of the
      management of patients after thoracotomy, yet the type of interventions utilized,
      and evidence for their efficacy, has not been established. The aim of the present
      study was to ascertain the current physiotherapy management of patients
      undergoing thoracotomy and the factors influencing practice among different
      providers. METHOD: A purpose-designed postal questionnaire was distributed to
      senior physiotherapists in all thoracic surgical units throughout Australia and
      New Zealand (n=57). RESULTS: A response rate of 81% was obtained (n=46). Pre
      operatively, 16 respondents (35%) reported assessing all thoracotomy patients.
      The majority of respondents (n=44; 96%) indicated that all patients were seen by
      physiotherapists after surgery, with 29 respondents (63%) performing prophylactic
      physiotherapy interventions to prevent post-operative pulmonary complications.
      Respondents reported that physiotherapy treatment was usually commenced on day
      one post-operatively (n=37; 80%) with the most commonly used treatment
      interventions being deep breathing exercises, the active cycle of breathing
      techniques, cough, forced expiration techniques and sustained maximal
      inspirations. Most respondents reported that patients first sat out of bed (n=41;
      89%), commenced shoulder range of movement (n=23; 50%) and walking (n=32; 70%) on
      day one post-operatively. The majority of respondents reported that they offered
      no post-operative pulmonary rehabilitation (n=25; 54%), outpatient follow-up
      (n=43; 94%) orpost-thoracotomy pain management (n=40; 87%). Respondents indicated
      that personal experience, literature recommendations and established practice
      were the factors which most influenced physiotherapy practice. Conclusion. Most
      patients after thoracotomy receive physiotherapy assessment and/or treatment in
      the immediate post-operative period, but only one-third were routinely seen pre
      operatively and relatively few were reviewed following discharge from hospital.
      Further studies are required to guide physiotherapists in determining the
      efficacy of their practices for patients undergoing thoracotomy.

PMID- 17536645
TI  - Mobility on discharge from an aged care unit.
AB  - BACKGROUND AND PURPOSE: Independent mobility is a crucial element of independent
      living and quality of life. However, little is known about the mobility of older
      people around the time of discharge from inpatient rehabilitation. The present
      study aimed to describe mobility on discharge from an aged care rehabilitation
      unit. METHOD: The study utilized a descriptive, cross-sectional design. Ninety
      five patients (mean age 81 (+/-8) years; 60% female) with diverse chronic
      conditions (median 5) who were able to walk at least 10m without weight-bearing
      restrictions were recruited from the aged care rehabilitation wards. Scores on
      the Barthel Index were obtained on admission and discharge to provide information
      about their overall level of function. Within the last week of rehabilitation
      stay, scores on the mobility and locomotion subsections of the Functional
      Independence Measure, gait velocity, and time and distance parameters of gait
      were obtained. Gait variables were measured by use of the GAITRite, an
      instrumented walkway. Medians and interquartile ranges (IQR) were reported for
      mobility variables. RESULTS: Following inpatient rehabilitation, many patients
      achieved independence in bed or chair transfers (83%), toilet transfers (81%),
      shower transfers (60%) and level-surface walking (74%). Only 31% achieved
      independence in stair climbing. Patients walked slowly at a median (IQR) gait
      velocity of 45.96 (31.51) cm/s and with markedly diminished cadence and step
      length. Subjects with a low number of chronic conditions generally performed
      better on mobility measures than those with a high number of chronic conditions.
      CONCLUSIONS: Although many older people are able to transfer and walk
      independently around the time of discharge from inpatient rehabilitation their
      mobility is still often impaired. For example, only 9.5% achieved a walking
      velocity considered to be adequate for street crossing and few demonstrated the
      ability to negotiate stairs. This highlights the need for ongoing rehabilitation
      for many of these older people. The possible cumulative effects of chronic
      conditions on mobility require further investigation.

PMID- 17536646
TI  - Weight distribution in standing and sitting positions, and weight transfer during
      reaching tasks, in seated stroke subjects and healthy subjects.
AB  - BACKGROUND AND PURPOSE: The recovery of sitting balance after a stroke is assumed
      to be essential to obtain independence in other vital functions. The purpose of
      the present study was to investigate weight distribution while sitting and
      standing still, and weight transfer during seated reaching tasks performed by
      stroke subjects and healthy subjects. METHOD: The study was cross-sectional.
      Twenty-one stroke subjects and 21 healthy subjects, matched by age and gender,
      participated. Main measures were weight distribution while standing and sitting
      still, and displacements of centre ofpressure (COP) during seated reaching tasks.
      Data were collected using a balance performance monitor (BPM), including
      software. RESULTS: Stroke subjects had less symmetrical weight distribution in
      standing than that of healthy subjects (p < 0.001). No significant differences
      between the groups were found while sitting still, and no associations between
      asymmetries in standing still and sitting positions within individual stroke
      subjects were found. Neither did the degree of weight distribution in sitting
      correspond to COP displacements in seated reaching tasks. However, COP
      displacement patterns in reaching tasks in the seated position were different in
      stroke subjects from those of healthy subjects. Stroke subjects showed more
      lateral displacement when reaching forwards (p < 0.001), and less lateral
      displacement when reaching sideways to the unaffected side (p = 0.01).
      CONCLUSION: COP displacement patterns in stroke subjects deviate more than those
      of healthy subjects in seated reaching tasks. The deviating COP displacement
      patterns are discussed as a possible dysfunction in the ability to make postural
      adjustments and learn an efficient movement pattern.

PMID- 17536648
TI  - Clinical relevance using timed walk tests and 'timed up and go' testing in
      persons with multiple sclerosis.
AB  - BACKGROUND AND PURPOSE: One must understand the potentials and limitations of all
      tests used to evaluate interventions. The aim of the present study was to clarify
      the reproducibility, smallest percentage difference needed to be able to detect a
      genuine change and correlation regarding the 10-m and 30-m timed walks (10TW
      30TW) and the 'timed up and go' (TUG) test in people with moderate multiple
      sclerosis (MS). METHOD: A repeated-measures design was used, with randomization
      into two groups and different time intervals used for testing. The 10TW and 30TW
      were performed three times and TUG twice at each testing. Self-selected speed was
      used for 10TW and forced speed (quickly but safely) for 30TW and TUG. Forty-three
      people were tested on three occasions within one week. Each person was tested at
      approximately the same time of the day and by the same physiotherapist on each
      occasion. RESULTS: The reproducibility was very high. For a single testing
      occasion, the intraclass correlation was 0.97 for the 10TW and 0.98 for the 30TW
      and TUG. The smallest percentage difference needed to be able to detect a genuine
      change in the entire study group was approximately -23% or +31% for either the
      1OTW or TUG. It was evident from the 30TW testing results that lower values
      applied to those with less (-14% to +17%) rather than more (-38% or +60%)
      disability. The correlation between all tests for the entire study group was 0.85
      (0.76-0.91). CONCLUSION: It is sufficient to use only one attempt and to choose
      only one of the tests when evaluating people with moderate MS. In the case of the
      30TW greater attention must be paid to the degree of disability when determining
      the smallest percentage difference needed to establish a genuine change, than

PMID- 17536647
TI  - Shoulder subluxation after stroke: relationships with pain and motor recovery.
AB  - BACKGROUND AND PURPOSE: Glenohumeral subluxation (GHS) is a frequent complication
      in patients with post-stroke hemiplegia, but its role in functional recovery is
      still unclear. The aim of the present investigation was to understand the
      relationship of GHS with shoulder pain and arm motor recovery. METHOD: A case
      control study design was used. A sample of 107 hemiplegic adults with recent
      stroke (less than 30 days from onset) was differentiated into two groups
      according to the presence of GHS. Motor recovery was assessed using the upper
      extremity part of the Fugl-Meyer Assessment Scale and the presence of shoulder
      pain was recorded at admission (T1), at discharge (T2) and at follow-up, 30-40
      days after discharge (T3). RESULTS: GHS was present in 52 patients (48.6%) and
      correlated significantly to shoulder pain at TI, at T2 and at T3 (p < 0.001).
      Moreover, GHS at admission accounted for nearly 50% of shoulder pain at T3
      (adjusted R2 = 0.458; p < 0.001). The presence of GHS was independently
      associated with the upper extremity score of the Fugl-Meyer Assessment Scale at
      follow-up (adjusted R2 = 0.766; p < 0.001). CONCLUSIONS: GHS is a factor
      associated with shoulder pain development and with arm motor recovery and should
      be treated in the acute stage of hemiplegia.

PMID- 17536649
TI  - Tests of walking ability at different speeds in patients with knee
      osteoarthritis.
AB  - BACKGROUND AND PURPOSE: Measurements of walking speeds are commonly used as an
      objective measure of functional performance in patients with knee osteoarthritis
      (OA) and are easily performed in a clinical setting. However, the choice in which
      the walking speed evaluation should be performed is controversial. The aim of
      this study was to identify the most discriminating walking speed after surgical
      interventions in patients with knee osteoarthritis, and to compare the
      responsiveness of the different gait speeds. METHOD: A prospective clinical one
      year follow-up study involving 54 patients with knee osteoarthritis (63 (+/-5)
      years of age) who were operated with either a unicompartmental knee arthroplasty
      or a high tibial osteotomy was undertaken. Thirty-nine patients had unilateral
      knee OA and 15 patients had bilateral knee OA or other symptoms from the lower
      extremities that could influence walking. The patients were examined at a gait
      laboratory before surgery, and one year after surgery. The patients were
      instructed to walk at slow, normal and fast walking speed. RESULTS: All patients
      (n=54) walked.faster one year after the surgical intervention compared to before
      surgery (p = 0.001) at slow (+15%), normal (+8%) and fast (+7%) walking speed.
      This increase was similar for the three walking speeds (p = 0.171). Patients with
      unilateral knee OA (n=39) reached an average change of +0.12 m/s, which was
      considered clinically important, while patients with bilateral knee OA (n=15) did
      not increase their walking speed > 0.12 m/s. Effect size was moderate for slow
      walking speed and small for normal and fast walking speeds, respectively.
      CONCLUSIONS: The different walking speeds were equally good in detecting changes
      one year after surgical interventions. In this study, responsiveness favoured
      slow walking speed, however, the advantages of normal walking speed are
      discussed.

PMID- 17536650
TI  - Beware reconfiguration fever!

PMID- 17536651
TI  - Do women take everything on offer, regardless?

PMID- 17536652
TI  - 'Born free from HIV' campaign.

PMID- 17536653
TI  - Nuchal cords: think before you check.

PMID- 17536654
TI  - Women in the driving seat: birth centre insights.

PMID- 17536655
TI  - VBAC: a mother's story.

PMID- 17536656
TI  - Reviewing the maternity services.

PMID- 17536657
TI  - A shoulder dystocia mnemonic for homebirth.
AB  - There are other shoulder dystocia mnemonics to be found on the internet, in
      obstetric textbooks and in assorted hospital protocols. Clearly there is mileage
      in the same mnemonic being used throughout hospital-based practice within the UK
      to avoid any confusion and streamline clinical practice, and the HELPERR mnemonic
      seems to have assumed this role admirably. However, for the midwife working at
      home it does not appear to be appropriate because: * it is not in the most useful
      order; * it does not allow for several other; manoeuvres that midwives have found
      helpful; * it is not always user-friendly and memorable. It is hoped that this
      article will prompt debate and discussion around the appropriate management of
      this rare emergency at home; and that midwives, should they choose, will be able
      to employ MAGIC R. PSAZZ as their mnemonic of choice in the homebirth setting.
      However, it is important to end by emphasising that no mnemonic or protocol
      should ever be more important than the clinical judgement of the clinician, which
      remains paramount throughout. The precise order of manoeuvres and actions will
      vary according to the situation and the midwife's communication with the woman,
      and her analytical and decision-making abilities remain crucial.

PMID- 17536658
TI  - Introducing the baby feeding law group.

PMID- 17536659
TI  - Midwifery basics: women's health needs (8). Women from disadvantaged communities.

PMID- 17536660
TI  - Blaming the baby.

PMID- 17536661
TI  - Our own worst enemies.

PMID- 17536662
TI  - Development and validation of a most-probable-numberimmunomagnetic separation
      methodology of enumerating Escherichia coli O157 in cattle feces.
AB  - A method to validate enumeration of Escherichia coli O157 in fecal samples from
      feedlot cattle was developed in these studies. Due to background flora, bovine
      fecal sample enumeration cannot be performed by simple direct plating techniques.
      Known quantities of E. coli O157:H7 were inoculated into feces, and populations
      were determined by direct plating of the cocktail (studies 1, 2, and 3) and
      manure and cocktail (studies 4 and 5) mixtures and compared with a most-probable
      number (MPN)-immunomagnetic separation (IMS) method. The three-tube MPN combined
      preenrichment in gram-negative broth with confirmation using IMS. Five separate
      enumeration studies (study 1, sterile feces inoculated with 10(2) E. coli O157:H7
      per g; study 2, nonsterile feces inoculated with 10(3) E. coli O157:H7 per g;
      study 3, nonsterile feces inoculated with 10(1) E. coli O157:H7 per g; study 4,
      sterile feces inoculated with 10(4) streptomycin-resistant E. coli O157:H7 per g;
      and study 5, sterile feces inoculated with 10(2) streptomycin-resistant E. coli
      O157:H7 per g) were conducted. These studies were performed to determine the
      precision, accuracy, and specificity at low and high levels of pathogen
      contamination in feces, using direct plating compared with the MPN-IMS
      methodology tested. There was an overall difference (P < 0.01) between direct
      plating and MPN-IMS methodologies, but this difference was biologically
      negligible due to the difference in least-squares means (0.29 +/- 0.10) being so
      low. The direct plating and MPN-IMS methods were correlated (r = 0.93). These
      results suggest that using the MPN-IMS procedures is an effective method of
      estimating E. coli O157 populations in naturally infected bovine fecal samples.

PMID- 17536663
TI  - Effects of a minimal hide wash cabinet on the levels and prevalence of
      Escherichia coli O157:H7 and Salmonella on the hides of beef cattle at slaughter.
AB  - Harborage of Escherichia coli O157:H7 and Salmonella on animal hides at slaughter
      is the main source of beef carcass contamination during processing. Given this
      finding, interventions have been designed and implemented to target the hides of
      cattle following entry into beef processing plants. Previous interventions
      targeting hides have not been suitable for all beef processing plants because of
      cost and space restrictions. In this study, a hide wash cabinet was evaluated to
      determine whether it was more amenable to widespread use in the beef processing
      industry, especially for small and medium-size plants. Overall, 101 (35.1%) of
      288 beef cattle hides sampled before entry into the hide wash cabinet harbored E.
      coli O157:H7 at or above the limit of detection (40 CFU/100 cm2). After passage
      through the hide wash cabinet, only 38 (13.2%) of 288 hides had E. coli O157:H7
      levels > or =40 CFU/100 cm2. Before the hide wash cabinet, 50 (17%) of 288 hides
      harbored E. coli O157:H7 at levels above 100 CFU/100 cm2, with one sample as high
      as 20,000 CFU/100 cm2. In contrast, only 14 (5%) of 288 hides had E. coli O157:H7
      levels above 100 CFU/100 cm2 after hide washing, with the highest being 2000
      CFU/100 cm2. These same trends also were found for Salmonella before and after
      hide washing. These results indicate that the hide wash cabinet described in this
      study was effective and should provide small and medium-size processing plants
      with an affordable hide wash intervention strategy.

PMID- 17536664
TI  - A real-time PCR assay for the detection of Salmonella in a wide variety of food
      and food-animal matricest.
AB  - Conventional culture methods have traditionally been considered the "gold
      standards" for the isolation and identification of foodborne pathogens. However,
      culture methods are labor-intensive and time-consuming. We have developed a real
      time PCR assay for the detection of Salmonella in a variety of food and food
      animal matrices. The real-time PCR assay incorporates both primers and
      hybridization probes based on the sequence of the Salmonella invA gene and uses
      fluorescent resonance energy transfer technology to ensure highly sensitive and
      specific results. This method correctly classified 51 laboratory isolates of
      Salmonella and 28 non-Salmonella strains. The method was also validated with a
      large number of field samples that consisted of porcine feces and cecal contents,
      pork carcasses, bovine feces and beef carcasses, poultry cecal contents and
      carcasses, equine feces, animal feeds, and various food products. The samples
      (3388) were preenriched in buffered peptone water and then selectively enriched
      in tetrathionate and Rappaport-Vassiliadis broths. Aliquots of the selective
      enrichment broths were combined for DNA extraction and analysis by the real-time
      PCR assay. When compared with the culture method, the diagnostic sensitivity of
      the PCR assay for the various matrices ranged from 97.1 to 100.0%, and the
      diagnostic specificity ranged from 91.3 to 100.0%. Kappa values ranged from 0.87
      to 1.00, indicating excellent agreement of the real-time PCR assay to the culture
      method. The reduction in time and labor makes this highly sensitive and specific
      real-time PCR assay an excellent alternative to conventional culture methods for
      surveillance and research studies to improve food safety.

PMID- 17536665
TI  - Efficacy of aqueous ozone for the decontamination of Escherichia coli O157:H7 and
      Salmonella on raspberries and strawberries.
AB  - The efficacy of ozone as a water additive for washing raspberries and
      strawberries was investigated. Pathogen-inoculated fruits were treated with
      aqueous ozone concentrations of 1.7 to 8.9 mg/liter at 20 degrees C for 2 to 64
      min, with an aqueous ozone concentration of 21 mg/liter at 4 degrees C for 64
      min, or with water as a control. Maximum pathogen reductions on raspberries were
      5.6 and 4.5 log CFU/g for Escherichia coli O157:H7 and Salmonella, respectively,
      at 4 degrees C, whereas reductions on strawberries were 2.9 and 3.3 log CFU/g for
      E. coli O157:H7 and Salmonella, respectively, at 20 degrees C after 64 min.
      Washing with water (sparging with air as control) resulted in reductions of
      approximately 1 log CFU/g. The results presented here indicate that aqueous ozone
      may be useful as a decontaminant for small fruits.

PMID- 17536666
TI  - Utilization of gaseous ozone for the decontamination of Escherichia coli O157:H7
      and Salmonella on raspberries and strawberries.
AB  - Each year in the United States, there are approximately 76 million foodborne
      illnesses, and fresh produce is the second most common vehicle for such
      illnesses. Before going to market, small fruits are not washed or treated in any
      manner to extend their shelf life. Washing alone is not a viable option, and the
      use of novel technologies should be investigated. One such technology is ozone
      treatment, which has been used with drinking water since the late 19th century.
      The efficacy of gaseous ozone for killing pathogens on strawberries and
      raspberries, which were used as a model for small fruits, was investigated in
      this study. Strawberries and raspberries were artificially contaminated with five
      strains of Escherichia coli O157:H7 and Salmonella enterica. Fruits were treated
      with four ozone treatments: (i) continuous ozone flow (5%, wt/wt) for 2, 4, 8,
      16, 32, and 64 min; (ii) pressurized ozone (83 kPa) for 2, 4, 8, 16, 32, and 64
      min; (iii) continuous ozone (64 min) followed by pressurized ozone (64 min); and
      (iv) vacuum followed by 64 min of pressurized ozone. Maximum reductions for both
      strawberries and raspberries were achieved with the third treatment scenario. On
      strawberries, 2.60- and 2.96-log reductions were achieved for Salmonella and E.
      coli O157:H7, respectively. For raspberries, 3.55- and 3.75-log reductions were
      achieved for Salmonella and E. coli O157:H7, respectively. These results indicate
      that gaseous ozone should be a useful treatment for decontamination of small
      fruits.

PMID- 17536667
TI  - Media for the aerobic resuscitation of Campylobacter jejuni.
AB  - The microaerophilic nature of Campylobacter jejuni has complicated its recovery
      from human and animal sources. In this study, enhancement of the growth and
      aerotolerance of C. jejuni ATCC 35921 in nutrient broth no. 2 (NB2) was
      investigated. The efficiency of recovery of C. jejuni in NB2 containing FBP
      (0.025% [each] ferrous sulfate, sodium metabisulfite, and sodium pyruvate), 5%
      laked horse blood, hemin, Oxyrase, or activated charcoal in an aerobic atmosphere
      was compared with that obtained under microaerophilic incubation. The shortest
      lag time (lamda) for cells grown aerobically was observed with NB2 supplemented
      with FBP, 5% laked horse blood, 0.01 g/liter of hemin, or 0.15 U/ml of Oxyrase.
      The efficacy of these media to resuscitate C. jejuni cells in late exponential
      phase, as well as cells subjected to stress induced by cold, heat, starvation, or
      acid, was determined in aerobic or microaerobic atmospheres. The h of cells grown
      aerobically in NB2 containing both FBP and blood was similar to that obtained in
      the same medium incubated in a microaerobic environment (P > 0.05). However, the
      X was longer during aerobic growth when low numbers of cells (approximately 1 log
      CFU/ml) in late exponential phase were used as the initial inoculum. The best
      recovery of stressed C. jejuni was observed in NB2 supplemented with FBP and
      blood and incubated aerobically. Enrichment in media incorporating FBP and 5%
      laked horse blood is a simple, convenient, and time-saving method to replace
      microaerophilic incubation methods for the resuscitation of C. jejuni.

PMID- 17536668
TI  - Application of multiplex PCR for monitoring colonization of pig tonsils by
      Yersinia enterocolitica, including biotype 1A, and Yersinia pseudotuberculosis.
AB  - A multiplex PCR assay was developed for the detection and differentiation of the
      Yersinia enterocolitica and Yersinia pseudotuberculosis isolates in both pure
      bacterial cultures and pig tonsils. The assay was based on the amplification of
      the ail, inv, yadA, and ystB genes. The PCR products, corresponding to the ail
      gene and the plasmid-borne yadA gene or only one product corresponding to the ail
      gene, were detected in Y. enterocolitica 4 biotype isolates. All of the Y.
      pseudotuberculosis isolates (n=6) tested gave a positive PCR reaction for the inv
      gene. For all tested Y. enterocolitica 1A biotype isolates (n=31), one product
      corresponding to the ystB gene was observed. The multiplex PCR assay was used to
      detect Y. enterocolitica and Y. pseudotuberculosis strains in pig tonsil samples
      obtained from 80 slaughtered pigs from three different herds. The presence of at
      least one of the specific PCR amplification products of ail-, ystB-, yadA-, and
      inv-specific sequences was observed in 11 samples (13.75%). These results of the
      multiplex PCR assay were compared with the results of conventional,
      microbiological testing. Y. enterocolitica isolates were cultured from only 3
      (3.75%) of the 80 pig tonsils examined. The multiplex PCR assay was shown to be
      an efficient tool for differentiation between the pYV plasmid-bearing Y.
      enterocolitica isolates, the plasmidless Y. enterocolitica isolates, the Y.
      enterocolitica biotype 1A isolates, and the Y. pseudotuberculosis isolates with
      and without the pYV plasmid in naturally contaminated pig tonsils. This indicates
      that this assay is useful to control food processing and track the source of
      contamination.

PMID- 17536669
TI  - Application of automated ribotyping to support the evaluation of Listeria
      monocytogenes sources in a Taleggio cheese producing plant.
AB  - In March 2005, Listeria monocytogenes was detected on the rinds of Taleggio
      cheeses produced in an Italian plant. To identify the pathogen source, 154 rinds
      of cheeses that had been manually and automatically salinated and 52
      environmental swabs collected from salting equipment, ripening cloths, and
      ripening boxes were tested for L. monocytogenes. Twenty-seven strains isolated
      from cheese samples and 16 strains isolated from environmental samples were
      genotyped by EcoRI and PvuII automated ribotyping. The microbiological results
      revealed a significant incidence of contamination of cheeses that were
      automatically salinated and contamination on the salting equipment, ripening
      cloths, and boxes. All cheese and environmental strains had the same EcoRI and
      PvuII ribotyping profiles, designated 153-204-S5 and 153-210-S-2, respectively.
      The only exception were three Taleggio strains, isolated from the same lot of
      product, that had EcoRI and PvuII ribotyping profiles designated 153-289-S6 and
      153-214-S-5, respectively. Strains with EcoRI profile 153-204-S5 were classified
      as DUP-ID 1045 and serotype 1/2a, whereas strains with EcoRI profile 153-289-S6
      were classified as DUP-ID 1034 and serotype 1/2b. The microbiological and
      molecular typing data collected in this study suggest that the source of the L.
      monocytogenes contamination in the Taleggio plant under study was the automated
      salting equipment. The isolate DUP-IDs were used to trace the introduction of
      potentially dangerous strains, such as those characterized as DUP-ID 1034, in the
      processing plant.

PMID- 17536670
TI  - Dose-response of Listeria monocytogenes after oral exposure in pregnant guinea
      pigs.
AB  - Listeriosis, a severe disease that results from exposure to the foodborne
      pathogen Listeria monocytogenes, is responsible for approximately 2500 illnesses
      and 500 deaths in the United States each year. Pregnant women are 20 times more
      likely to develop listeriosis than the general population, with adverse pregnancy
      outcomes that include spontaneous abortions, stillbirths, and neonatal
      meningitis. The objective of this study was to determine an infective dose that
      resulted in stillbirths and infectivity of selected tissues in pregnant guinea
      pigs. Pregnant guinea pigs were exposed orally on gestation day 35 to 10(4) to
      10(8) L. monocytogenes CFU in sterile whipping cream. L. monocytogenes was
      recovered at 64, 73, 90, and 100% from the livers of animals infected with 10(5),
      10(6), 10(7), and 10(8) CFU, respectively. In dams exposed to > or =10(6) CFU, L.
      monocytogenes was cultured from 50% of the spleen samples and 33% of the
      gallbladder samples. Eleven of 34 dams infected with > or =10(6) CFU delivered
      stillborn pups. L. monocytogenes was cultured from the placenta, liver, and brain
      tissue of all stillbirths. Dams that delivered nonviable fetuses after treatment
      with > or =10(7) L. monocytogenes CFU had fecal samples positive for L.
      monocytogenes at every collection posttreatment. On the basis of a log-logistic
      model, the dose that adversely affected 50% of the pregnancies was approximately
      10(7) L. monocytogenes CFU compared with that estimated from a human outbreak of
      106 CFU. Listeriosis in pregnant guinea pigs can result in stillbirths, and the
      overall disease is similar to that described in nonhuman primates and in humans.

PMID- 17536671
TI  - Proteomic analysis of a hypochlorous acid-tolerant Listeria monocytogenes
      cultural variant exhibiting enhanced biofilm production.
AB  - Following exposure of Listeria monocytogenes Scott A (SA) to hypochlorous acid,
      rough colony variants were identified that were tolerant of hypochlorous acid and
      produced increased amounts of biofilm. A derivative of one of these variants was
      smooth, produced even more biofilm, and exhibited greater biofilm chlorine
      resistance. The objective of this research was to compare the protein expression
      of a cultural variant to SA and to identify proteins that might be associated
      with biofilm production and chlorine tolerance. Suspension chlorine tolerance for
      several cultural variants (SAR, SAR5, and SBS) was determined by exposure to 60
      to 120 ppm of hypochlorous acid for 5 min. Hypochlorous acid tolerance of
      biofilms was determined after growing biofilms on stainless steel and then
      exposing them to 200 ppm of hypochlorous acid for 5 min. All cultural variants
      were able to survive 120 ppm of hypochlorous acid in suspension. There was little
      difference in the hypochlorous acid tolerance of the cultural variant planktonic
      cells. The cultural variants produced greater amounts of biofilm than the common
      form of L. monocytogenes and were more tolerant of hypochlorous acid. The SBS
      variant was selected for proteomic comparison because it was the variant that
      produced the most biofilm and was the most tolerant of hypochlorous acid when
      grown as a biofilm. Protein expression of planktonic and biofilm cells of SBS was
      compared to SA by two-dimensional difference gel electrophoresis. The 50s
      ribosomal protein, L10, was down-regulated in biofilm SBS. Other proteins down
      regulated in planktonic SBS were the peroxide resistance protein (Dpr) and a
      sugar-binding protein (LMO0181). This sugar-binding protein was also up-regulated
      in biofilm SBS. One protein spot down-regulated in planktonic SBS contained both
      50s ribosomal protein L7/L12 and an unknown protein (LM01888).

PMID- 17536672
TI  - Extracting additional risk managers information from a risk assessment of
      Listeria monocytogenes in deli meats.
AB  - The risk assessment study of Listeria monocytogenes in ready-to-eat foods
      conducted by the U.S. Food and Drug Administration is an example of an extensive
      quantitative microbiological risk assessment that could be used by risk analysts
      and other scientists to obtain information and by managers and stakeholders to
      make decisions on food safety management. The present study was conducted to
      investigate how detailed sensitivity analysis can be used by assessors to extract
      more information on risk factors and how results can be communicated to managers
      and stakeholders in an understandable way. The extended sensitivity analysis
      revealed that the extremes at the right side of the dose distribution (at
      consumption, 9 to 11.5 log CFU per serving) were responsible for most of the
      cases of listeriosis simulated. For concentration at retail, values below the
      detection limit of 0.04 CFU/g and the often used limit for L. monocytogenes of
      100 CFU/g (also at retail) were associated with a high number of annual cases of
      listeriosis (about 29 and 82%, respectively). This association can be explained
      by growth of L. monocytogenes at both average and extreme values of temperature
      and time, indicating that a wide distribution can lead to high risk levels.
      Another finding is the importance of the maximal population density (i.e., the
      maximum concentration of L. monocytogenes assumed at a certain temperature) for
      accurately estimating the risk of infection by opportunistic pathogens such as L.
      monocytogenes. According to the obtained results, mainly concentrations
      corresponding to the highest maximal population densities caused risk in the
      simulation. However, sensitivity analysis applied to the uncertainty parameters
      revealed that prevalence at retail was the most important source of uncertainty
      in the model.

PMID- 17536673
TI  - Occurrence of toxigenic Staphylococcus aureus in ready-to-eat food in Korea.
AB  - Toxigenic Staphylococcus aureus contamination in ready-to-eat (RTE) food is a
      leading cause of foodborne illness in Korea. To monitor food contamination by S.
      aureus, a total of 3332 RTE food samples were selected from nationwide wholesale
      marts between 2003 and 2004 and examined. A total of 285 (8.6%) of the overall
      samples were contaminated by S. aureus. According to the analysis, 31.6% of the
      tested cream-cakes, 19.8% of the raw fish, and 19.3% of the rice cakes with
      filling were contaminated with S. aureus. Forty-seven percent of the strains
      isolated from the contaminated food were enterotoxigenic S. aureus. The
      phenotypic result of the strain isolated from food showed that 48% of the strains
      produced one or more toxins, such as staphylococcal enterotoxins A, B, and C
      (SEA, SEB, and SEC). At least one SEA was produced by over 90% of the toxigenic
      strains. Other toxins, such as SEB, SEC, SED, SEA+SEC, and SEC+SED, were each
      detected. Toxic shock syndrome toxin 1 (TSST-1), a causative agent of toxic shock
      syndrome, was detected in 13 strains of the toxigenic isolates from the food. As
      the result of genotyping, 22 strains with a toxin gene that was not detected in
      the phenotypic analysis were also detected. Sixty-nine percent of the toxigenic
      strains had at least one sea gene, and the most prevalent genotype was sea+seh
      (34.4%), followed by sea (18.8%) and sea+seg+sei (15.6%). The tst gene encoding
      TSST-1 was found in 13 strains (13.5%). The genes (eta and etb) encoding
      exfoliative toxins A and B were not detected in any of the samples.

PMID- 17536674
TI  - Effects of modified atmosphere packaging on toxin production by Clostridium
      botulinum in raw aquacultured summer flounder fillets (Paralichthys dentatus).
AB  - Packaging fishery products under vacuum atmosphere packaging (VAC) and modified
      atmosphere packaging (MAP) conditions can significantly extend the shelf life of
      raw, refrigerated fish products. There is considerable commercial interest in
      marketing VAC and MAP refrigerated (never frozen) raw fish fillets. The objective
      of this study was to determine if Clostridium botulinum toxin development
      precedes microbiological spoilage in raw, refrigerated flounder fillets.
      Aquacultured flounder (Paralichthys dentatus) individual fish fillets either were
      packed with a film having an oxygen transmission rate (OTR) of 3000 cm3 m(-2) 24
      h(-1) at 22.8 degrees C or were vacuum packaged or packaged under 100% CO2 with a
      film having an OTR of 7.8 cm3 m(-2) 24 h(-1) at 21.1 degrees C and were stored at
      4 and 10 degrees C. Samples were analyzed by aerobic plate count (APC) for
      spoilage and qualitatively for botulinum toxin with a mouse bioassay. The results
      demonstrate that flounder fillets (4 degrees C) packaged with a film having an
      OTR of 3,000 were microbiologically spoiled (APC, > 10(7) CFU/g) on day 15, but
      there was no toxin formation, even after 35 days of storage. However, at 10
      degrees C, toxin production occurred (day 8), but it was after microbial spoilage
      and absolute sensory rejection (day 5). Vacuum-packaged fillets and 100% CO2
      fillets (4 degrees C) packaged with a film having an OTR of 7.8 were toxic on
      days 20 and 25, respectively, with microbial spoilage (APC, >10(7) CFU/g) not
      occurring during the tested storage period (i.e., >35 days). At 10 degrees C, in
      vacuum-packaged flounder, toxin formation coincided with microbiological spoilage
      (days 8 to 9). In the 100% CO2-packaged fillets, toxin formation occurred on day
      9, with microbial spoilage occurring on day 15. This study indicates that films
      with an OTR of 3,000 can be used for refrigerated fish fillets and still maintain
      the safety of the product.

PMID- 17536675
TI  - Differentiation and characterization by molecular techniques of Bacillus cereus
      group isolates from poto poto and degue, two traditional cereal-based fermented
      foods of Burkina Faso and Republic of Congo.
AB  - Poto poto (a maize sourdough) and degue (a pearl millet-based food) are two
      traditional African fermented foods. The molecular biology of toxigenic and
      pathogenic bacteria found in those foods is largely unknown. The purpose of this
      study was to study the phylogenetic relatedness and toxigenic potential of 26
      Bacillus cereus group isolates from these traditional fermented foods. The
      relatedness of the isolates was evaluated with repetitive element sequence-based
      PCR (REP-PCR) and 16S rDNA sequencing analysis. A multiplex real-time PCR assay
      targeting the lef and capC genes of B. anthracis pXO1 and pXO2 plasmids and the
      sspE chromosomal gene of B. cereus and B. anthracis also was carried out. Melting
      curve analysis of the sspE amplification product was used to differentiate B.
      cereus from B. anthracis, and the presence of the B. cereus enterotoxin genes was
      determined with PCR amplification. Isolates had 15 different REP-PCR profiles,
      according to which they could be clustered into four groups. 16S rDNA sequencing
      analysis identified 23 isolates as B. cereus or B. anthracis and three isolates
      as B. cereus or Bacillus sp. Multiplex real-time PCR amplification indicated the
      absence of the lef and capC genes of B. anthracis pXO 1 and pXO2 plasmids, and
      melting curve analysis revealed amplification of the 71-bp sspE product typical
      of B. cereus in all isolates instead of the 188-bp amplicon of B. anthracis,
      confirming the identity of these isolates as B. cereus. Four isolates had
      amylolytic activity. All isolates had lecithinase activity and beta-hemolytic
      activity. Enterotoxin production was detected in two isolates. The emetic toxin
      gene was not detected in any isolate. The nheB toxin gene was detected in 19
      isolates by PCR amplification; one of these isolates also contained the hblD (L1)
      gene. The cytotoxin K cytK-1 gene was not detected, but the cytK-2 gene was
      clearly detected in six isolates.

PMID- 17536676
TI  - Decontamination of beef subprimal cuts intended for blade tenderization or
      moisture enhancement.
AB  - The prevalence of Escherichia coli O157:H7 on beef subprimal cuts intended for
      mechanical tenderization was evaluated. This evaluation was followed by the
      assessment of five antimicrobial interventions at minimizing the risk of
      transferring E. coli O157:H7 to the interior of inoculated subprimal cuts during
      blade tenderization (BT) or moisture enhancement (ME). Prevalence of E. coli
      O157:H7 on 1,014 uninoculated beef subprimals collected from six packing
      facilities was 0.2%. Outside round pieces inoculated with E. coli O157:H7 at
      10(4) CFU/100 cm2 were treated with (i) no intervention, (ii) surface trimming,
      (iii) hot water (82 degrees C), (iv) warm 2.5% lactic acid (55 degrees C), (v)
      warm 5.0% lactic acid (55 degrees C), or (vi) 2% activated lactoferrin followed
      by warm 5.0% lactic acid (55 degrees C) and then submitted to BT or ME.
      Prevalence (n=196) of internalized (BT and ME) E. coli O157:H7 was 99%.
      Enumeration of E. coli 0157:H7 (n=192) revealed mean surface reductions of 0.93
      to 1.10 log CFU/100 cm2 for all antimicrobial interventions. E. coli O157:H7 was
      detected on 3 of the 76 internal BT samples and 73 of the 76 internal ME samples.
      Internal ME samples with no intervention had significantly higher mean E. coli
      O157:H7 populations than did those internal samples treated with an intervention,
      but there were no significant differences in E. coli O157:H7 populations among
      internal BT samples. Results of this study demonstrate that the incidence of E.
      coli O157:H7 on the surface of beef subprimal cuts is low and that interventions
      applied before mechanical tenderization can effectively reduce the transfer of
      low concentrations of E. coli O157:H7 to the interior of beef subprimal cuts.

PMID- 17536677
TI  - Microbiological and color aspects of cooked sausages made from a standardized
      porcine blood cell concentrate.
AB  - The objective of this study was to determine the potential for blood cell
      concentrates (BCCs) from pigs as an ingredient in food. Sausages were made for
      this study according to a basic recipe for a type of blood sausage that is common
      in Germany. First, sausages were produced with rind and kettle broth only, and
      different amounts (2.5 to 31%) of standardized blood cell concentrate (s-BCC)
      were added (15% table salt [NaCl] and 25% protein content). Then, sausages were
      made with whole blood and compared with s-BCC sausages; both the BCC and blood
      had been pretreated either with NaCl or curing salt (nitrite). The impact of BCC
      and blood on the color (La*b*) of these rind sausages was determined. Finally,
      blood sausages were made with 12% s-BCC and either natural spices or spice
      extracts. These sausages were investigated microbiologically and compared to
      customary commercial blood sausage products (with whole blood) in terms of
      aerobic plate count (APC), Enterobacteriaceae, sulfite-reducing anaerobic
      bacteria, coagulase-positive staphylococci, and spore-forming bacilli. The
      desired color parameters (L, 34.5; a*, 17.8; and b*, 10.6) were obtained with the
      addition of about 12% s-BCC. Curing the blood or BCC beforehand had no
      significant (P > 0.05) influence on the color. The microbial counts of both the
      blood (APC, 4.4 log CFU/g) and the natural spices (APC, 6.6 log CFU/g) were
      relatively high. The spices were responsible for the relatively high microbial
      counts in the sausages, particularly the bacilli (6.4 log CFU/g). However, these
      counts were comparable to those found in commercial blood sausages. The bacteria
      introduced into the sausage by the blood had no significant impact on the
      bacterial counts of the end product. The bacterial loads of the sausages produced
      with 12% s-BCC and spice extracts were significantly lower (APC and bacilli, 2.0
      log CFU/g) than those of the other blood sausages (APC, -4.4 log CFU/g; bacilli,
      3.2 to 4.0 log CFU/g).

PMID- 17536678
TI  - Microbial levels in Michigan apple cider and their association with manufacturing
      practices.
AB  - In recent decades, apple cider has been implicated in a series of outbreaks of
      foodborne illness. The objective of this study was to determine the presence and
      concentrations of pathogenic and indicator microorganisms in apple cider
      processed in Michigan and to evaluate the impact of thermal pasteurization, UV
      light radiation, and implementation of hazard analysis critical control point
      (HACCP) plans on these microbes. Cider samples were obtained from Michigan mills
      between 1997 and 2004 and analyzed for Escherichia coli O157:H7, Salmonella,
      generic E. coli, total coliforms, and aerobic bacteria. Neither E. coli O157:H7
      nor Salmonella were detected in any tested cider samples, suggesting a very low
      frequency of pathogens in Michigan apple cider. The persistent and relatively
      high frequency of generic E. coli observed in samples obtained in all years
      indicates a continued risk of pathogen contamination in Michigan apple cider,
      especially when it is untreated. The use of thermal pasteurization or UV light
      radiation and reported implementation of HACCP plans were associated with lower
      frequency and counts of generic E. coli, total coliforms, and aerobic
      microorganisms. However, the relatively high counts of indicator organisms in
      some cider samples that were claimed to be treated according to these pathogen
      reduction measures indicates that some processors had inadequate practices,
      facilities, or equipment for pathogen reduction or did not consistently or
      adequately apply practices or pathogen-reduction equipment in an effective
      manner.

PMID- 17536679
TI  - Antimicrobial activity of olive oil, vinegar, and various beverages against
      foodborne pathogens.
AB  - The survival of foodborne pathogens in aqueous extracts of olive oil, virgin
      olive oil, vinegar, and several beverages was evaluated. Vinegar and aqueous
      extracts of virgin olive oil showed the strongest bactericidal activity against
      all strains tested. Red and white wines also killed most strains after 5 min of
      contact, black and green tea extracts showed weak antimicrobial activity under
      these conditions, and no effect was observed for the remaining beverages (fruit
      juices, Coca-Cola, dairy products, coffee, and beer). The phenolic compound
      content of the aqueous olive oil and virgin olive oil extracts could explain
      their antibacterial activity, which was also confirmed in mayonnaises and salads
      used as food models. Virgin olive oil in mayonnaises and salads reduced the
      counts of inoculated Salmonella Enteritidis and Listeria monocytogenes by
      approximately 3 log CFU/g. Therefore, olive oil could be a hurdle component in
      certain processed foods and exert a protective effect against foodborne pathogens
      when contaminated foods are ingested.

PMID- 17536680
TI  - Evaluation of PCR-single-strand conformational polymorphism analysis for
      identification of gram-negative histamine-producing bacteria isolated from fish.
AB  - In this study, the previously established PCR-single-strand conformation
      polymorphism (SSCP) system for detecting and identifying gram-negative histamine
      producing bacteria was evaluated. This system can detect and identify histamine
      producing bacteria directly from seafood by the use of sequence polymorphisms of
      the histidine decarboxylase gene (hdc). First, we isolated 81 histamine-producing
      strains of bacteria from fish samples and analyzed the hdc gene by the PCR-SSCP
      system. The 22 newly obtained SSCP banding patterns were added to our database,
      and the utility of our modified database was tested in a second experiment
      consisting of 18 strains of histamine-producing bacteria isolated from 25 fish
      samples. Approximately 80% of the histamine-producing strains corresponded to
      those in the new database. Use of the database for PCR-SSCP analysis, including
      the band patterns newly added in this study, for the hdc gene makes it possible
      to more accurately identify histamine producers.

PMID- 17536681
TI  - Inhibition of Aspergillus spp. and Penicillium spp. by fatty acids and their
      monoglycerides.
AB  - The antifungal activity of three fatty acids (lauric, myristic, and palmitic
      acids) and their monoglycerides (monolaurin, monomyristic acid, and palmitin,
      respectively) against Aspergillus and Penicillium species in a model system was
      investigated. Data were modeled through a reparameterized Gompertz equation. The
      maximum colony diameter attained within the experimental time (30 days), the
      maximal radial growth rate, the lag time (i.e., the number of days before the
      beginning of radial fungal growth), and the minimum detection time (MDT; the
      number of days needed to attain 1 cm colony diameter) were evaluated. Fatty acids
      and their monoglycerides inhibited mold growth by increasing MDT and lag times.
      The effectiveness of the active compounds seemed to be strain and genus
      dependent. Palmitic acid was the most effective chemical against aspergilli,
      whereas penicilli were strongly inhibited by myristic acid. Aspergilli also were
      more susceptible to fatty acids than were penicilli, as indicated by the longer
      MDT.

PMID- 17536682
TI  - Consumer knowledge and use of open dates: results of a WEB-based survey.
AB  - Consumers are relying increasingly on ready-to-eat (RTE) foods because they are
      convenient, quick, and easy. Open dates let consumers know by which date to
      purchase or use RTE foods for best quality. To further characterize consumer
      knowledge and use of open dates for specific refrigerated RTE foods (smoked
      seafood, cooked crustaceans, bagged salads, prewashed cut produce, soft cheeses,
      frankfurters, deli meats, fermented sausages, and deli salads), we conducted a
      nationally representative web-enabled survey (n=2060). Before purchasing RTE
      foods, 48 to 68% of respondents check open dates all or most of the time. Before
      preparing RTE foods, 43 to 64% of respondents check open dates all or most of the
      time. Nearly two-thirds of respondents reported that their senses were the most
      important factors in deciding whether to eat a refrigerated food, which is an
      unsafe practice. About one-third of respondents reported that an open date is the
      most important factor in deciding whether to eat a refrigerated food. Many
      respondents, however, do not understand the meanings of the different types of
      dates. Only 18% correctly defined the use-by date. The findings suggest consumers
      could benefit from education regarding open dates and recommended storage times
      for RTE foods.

PMID- 17536683
TI  - Using expert elicitation to link foodborne illnesses in the United States to
      foods.
AB  - U.S. foodborne illness risk analysis would benefit greatly from better
      information on the relationship between the incidence of foodborne illness and
      exposure to foodborne pathogens. In this study, expert elicitation was used to
      attribute U.S. foodborne illnesses caused by the nine FoodNet pathogens,
      Toxoplasma gondii, and noroviruses to consumption of foods in 11 broad
      categories. Forty-two nationally recognized food safety experts responded to a
      formal written expert elicitation survey. For each pathogen, respondents gave
      their best estimate of the distribution of foodborne illnesses associated with
      each of the food categories and the 90% confidence bounds on each of their
      estimates. Based on the work of Paul Mead and his coauthors, food attribution
      percentage estimates from this study were used to attribute case,
      hospitalization, and death incidence estimates to foods according to pathogen.
      These attribution estimates indicate that 15 food-pathogen pairs account for 90%
      of the illnesses, 25 pairs account for 90% of hospitalizations, and 21 pairs
      account for 90% of deaths.

PMID- 17536684
TI  - Food safety practices among pregnant women and mothers in the women, infants, and
      children program, Miami, Florida.
AB  - Pregnant women and infants are two groups at the highest risk of severe outcomes
      from foodborne illnesses. We surveyed adult clients of a Women, Infants, and
      Children (WIC) clinic serving predominately African Americans in inner-city
      Miami, Florida, to assess food safety practices. Eligible and consenting women
      completed a 23-item self-administered survey with questions concerning food
      handling practices around the Partnership for Food Safety Education's Fight BAC!
      campaign constructs of "clean", "separate" (not cross-contaminated), "cook", and
      "chill". Of 342 eligible clients, 299 (87.4%) consented to participate. In
      general, the clients' food safety practices were most problematic in the cook and
      chill constructs. Using a cooking thermometer, refrigerating foods within 2 h,
      and thawing them safely were the least commonly reported safe practices. Women
      who were pregnant with their first child had the lowest food safety practice
      scores. Of the 62 pregnant participants, 32 (51.6%) reported eating hot dogs or
      deli meats without first reheating them some of the time or more often, and 22
      (35.5%) reported eating soft cheeses and blue-veined cheeses some of the time or
      more often, putting the women at risk of listeriosis. Although all women in the
      WIC program could benefit from food safety education, these findings indicate
      that women during their first pregnancy should especially be targeted for food
      safety education.

PMID- 17536685
TI  - Prevalence of Salmonella in grade A whole shell eggs in the island of Ireland.
AB  - Following the emergence of Salmonella Enteritidis as a widespread contaminant of
      eggs and the role of eggs in the transmission of human salmonellosis, control
      measures were introduced to curb the spread of infection. Two approaches to
      Salmonella control are currently used by egg producers in Ireland, because
      Northern Ireland producers, like those in the rest of the United Kingdom, widely
      adopted a vaccination regime, whereas the Republic of Ireland does not permit
      vaccination but introduced controls based on routine monitoring for specific
      Salmonella serovars and subsequent culling of infected flocks. To compare the
      efficacy of these two approaches and determine the prevalence of salmonellae in
      eggs produced for retail sale in the island of Ireland, a major survey of
      approximately 30,000 grade A eggs was undertaken. Egg shells and contents were
      analyzed separately for salmonellae by procedures based on International
      Organization for Standardization methodology. The survey yielded only two
      positive samples, with Salmonella Infantis and Salmonella Montevideo isolated
      from shells; no egg contents yielded salmonellae. There was no statistically
      significant difference in the prevalence of salmonellae between eggs produced in
      Northern Ireland and those from the Republic of Ireland; hence, both regimes
      appeared to be equally effective in controlling salmonellae. The prevalence was
      also significantly lower than that found in a recent major United Kingdom survey.
      Hence, shell eggs produced in the island of Ireland are unlikely to be a source
      of human salmonellosis.

PMID- 17536686
TI  - Application of a novel hydrophilic infrared-transparent membrane to the
      differentiation between microcolonies of Enterobacter sakazakii and Klebsiella
      pneumoniae.
AB  - A proof-of-concept study is reported for the differentiation between
      microcolonies of Enterobacter sakazakii and Klebsiella pneumoniae by means of a
      novel sample preparation for infrared (IR) analysis. A disposable, IR
      transparent, microporous (0.2-microm pores), hydrophobic, polyethylene (PE)
      membrane (51 microm thick) was plasma treated under an oxygen atmosphere and used
      to (i) filter (or print microarrays of) dilute aqueous foodborne bacterial
      suspensions and (ii) subsequently grow bacterial microcolonies when the treated,
      hydrophilic PE membrane was placed over brain heart infusion agar medium and
      incubated. Because this unique membrane is transparent to IR light, isolated
      microcolonies (200 microm) of bacterial cells grown on this PE substrate for the
      first time could be directly fingerprinted by IR microspectroscopy in the
      transmission mode. Hence, time-consuming bacterial cell transfer from culture
      plates to an IR sample holder for subsequent measurement by IR spectroscopy was
      eliminated. Multivariate analysis of the observed IR spectra for microcolonies
      allowed the rapid differentiation between E. sakazakii and K. pneumoniae.

PMID- 17536687
TI  - Salmonella diagnosis in pig production: methodological problems in monitoring the
      prevalence in pigs and pork.
AB  - Salmonellosis is an important foodborne infection in industrialized and
      developing countries. Especially for human Salmonellosis caused by Salmonella
      enterica serovar Typhimurium, pigs and pork are the major sources of infection.
      Mitigation and control strategies that result from surveillance programs attempt
      to reduce or even eradicate Salmonella in pork to lower consumers' risks. The
      methodology for Salmonella screening in pigs is generally based on antibody
      detection at slaughter with meat juice as the sample matrix. The instructions to
      most commercial enzyme-linked immunosorbent assay (ELISA) kits for the detection
      of Salmonella antibodies state that their product is suitable for antibody
      detection in meat juice and sera. In the present study, we show that it is
      essential to recalculate the percent optical density (OD%) data obtained from
      meat juice by the ELISA (IDEXX HerdCheck swine Salmonella) by the following
      regression equation: OD%sera = -70.5587 + 128.1490/ {1 + exp[(-18.8969 -
      OD%meatjuice)/27.6032]}(1.1771), r = 0.87, to compare results with those obtained
      from sera. By this regression equation, we were able to compare the Salmonella
      antibody levels (classified as <10, 10 to <20, 20 to <40, and > or =40 OD%) for
      sows, growers, and slaughter pigs. We identified significantly higher numbers of
      growers with lower OD% levels than for sows and slaughter pigs. Without a
      recalculation of the meat juice results, the higher fraction of samples with low
      OD% values led to an underestimation of the actual seroprevalence.

PMID- 17536688
TI  - A survey of the microbiological quality of kangaroo carcasses processed for human
      consumption in two processing plants in Queensland, Australia.
AB  - An investigation of the microbiological quality of kangaroo carcasses at two
      Queensland processing plants was carried out. A total of 836 whole muscle samples
      were taken, 801 from plant A and 35 from plant B. Samples were analyzed for
      aerobic bacteria, Escherichia coli, and Salmonella. The mean adjusted aerobic
      plate count (APC) was 2.8 log CFU/g, and counts at the 90th, 95th, and 99th
      percentiles were 4.2, 4.9, and 6.4 log CFU/g, respectively. The maximum number of
      bacteria recovered was 6.5 log CFU/g. E. coli was detected in 13.9% of samples,
      for which the adjusted mean was 0.7 log CFU/g, and counts at the 90th, 95th, and
      99th percentiles were 1.4, 2.0, and 3.0 log CFU/g, respectively. Salmonella was
      detected in 0.84% of samples. There was no significant relationship (P < 0.05)
      between season and APC or E. coli count. There was a significant relationship (P
      < 0.001) between Salmonella prevalence and summer. The microbiological quality of
      Queensland kangaroo carcasses is similar to that obtained during other excision
      based studies of kangaroo, wild boar, and beef carcasses.

PMID- 17536689
TI  - Prevalence and enumeration of Escherichia coli O157 in steers receiving various
      strains of Lactobacillus-based direct-fed microbials.
AB  - The objective of this research was to evaluate the effect of daily dietary
      inclusion of specific strains of Lactobacillus acidophilus on prevalence and
      concentration of Escherichia coli O157 in harvest-ready feedlot cattle. Five
      hundred yearling steers were housed in pens of 10 animals each. At arrival,
      steers were randomly allocated to one of five cohorts. Four of the cohorts were
      fed various strains and dosages of Lactobacillus-based direct-fed microbials
      throughout the feeding period. Fecal samples were collected from the rectum of
      each animal immediately prior to shipment to the abattoir. E. coli O157 was
      detected using selective enrichment and immunomagnetic separation techniques. For
      positive samples, E. coli O157 concentration was estimated using a most-probable
      number (MPN) technique that included immunomagnetic separation. Prevalence varied
      among the cohorts (P < 0.01). The prevalence in the controls (26.3%) was greater
      (P < 0.05) than that in cattle supplemented with L. acidophilus strains NP51,
      NP28, or NP51-NP35 (13.0, 11.0, and 11.0%, respectively). The greatest E. coli
      O157 concentration was also observed in the controls (3.2 log MPN/g of feces);
      this concentration was greater (P < 0.05) than that observed in positive animals
      receiving NP51, NP28, or NP51-NP35 (0.9, 1.1, 1.7 log MPN/g of feces,
      respectively). Specific strains of Lactobacillus-based direct-fed microbials
      effectively reduced the prevalence and concentration of E. coli O157 in harvest
      ready cattle, whereas others did not. When using direct-fed microbials to reduce
      carriage of E. coli O157 in cattle, it is important to select appropriately
      validated products.

PMID- 17536690
TI  - Inhibitory activity of colicin E1 against Listeria monocytogenes.
AB  - Colicins are gram-negative bacteriocins produced by and effective against
      Escherichia coli and related species. Colicin E1 (ColE1) is composed of three
      functional domains, which collectively have a pore-forming effect on targeted
      bacteria. ColE1 binding and translocation domains are highly specific in contrast
      to the pore-forming domain, implying that ColE1 could be broadly effective. In
      this study, the activity of ColE1 against Listeria monocytogenes was evaluated in
      broth and on surfaces of ready-to-eat products. Individual strains of L.
      monocytogenes were examined in broth containing ColE1 at 0, 0.1, 1, or 10
      microg/ml. Although strain differences in sensitivity to ColE1 existed, growth
      was significantly reduced in all strains at doses as low as 0.1 microg/ml.
      Sterilized ham slices were submerged in a five-strain L. monocytogenes cocktail
      (either 7 or 4 log CFU/ ml) and placed in vacuum packages containing 0, 1, 5, 10,
      25, or 50 microg of ColE1. Ham slices were then stored at 4 or 10 degrees C, and
      samples were removed and examined for L. monocytogenes after 1, 3, 7, and 14
      days. Reduction of L. monocytogenes by ColE1 was dependent on initial inoculum
      concentration and storage temperature. For slices stored at 4 degrees C,
      treatment with 25 microg reduced Listeria growth below detection limits for the
      slices inoculated with 4 log CFU/ml for the entire 14 days, whereas for the 7-log
      CFU/ml slices, growth was detected at 7 days postinoculation. For slices stored
      at 10 degrees C, 10 microg/ml ColE1 significantly inhibited growth of L.
      monocytogenes for up to 3 days for both inoculation groups. These data indicate
      that ColE1 is highly effective against Listeria.

PMID- 17536691
TI  - Use of one-ply composite tissues in an automated optical assay for recovery of
      Listeria from food contact surfaces and poultry-processing environments.
AB  - A novel one-ply composite tissue (CT) method using the Soleris (formerly BioSys)
      optical analysis system was compared with the conventional U.S. Department of
      Agriculture (USDA) environmental sponge enrichment method for recovery of
      Listeria from food contact surfaces and poultry-processing environments.
      Stainless steel and high-density polyethylene plates were inoculated to contain a
      six-strain L. monocytogenes cocktail at 10(4), 10(2), and 10 CFU per plate,
      whereas samples from naturally contaminated surfaces and floor drains from a
      poultry-processing facility were collected with CTs and environmental sponges. CT
      samples were transferred into Soleris system vials, and presumptive-positive
      samples were further confirmed. Sponge samples were processed for Listeria using
      the USDA culture method. L. monocytogenes recovery rates from inoculated
      stainless steel and polyethylene surfaces were then compared for the two methods
      in terms of sensitivity, specificity, and positive and negative predictive
      values. No significant differences (P > 0.05) were found between the two methods
      for recovery of L. monocytogenes from any of the inoculated stainless steel and
      polyethylene surfaces or environmental samples. Sensitivity, specificity, and
      overall accuracy of the CT-Soleris for recovery of Listeria from environmental
      samples were 83, 97, and 95%, respectively. Listeria was detected 2 to 3 days
      sooner with the CT-Soleris method than with the USDA culture method, thus
      supporting the increased efficacy of this new protocol for environmental
      sampling.

PMID- 17536692
TI  - Effectiveness and stability of plastic films coated with nisin for inhibition of
      Listeria monocytogenes.
AB  - Plastic films were coated with a cellulose-based carrier solution containing
      nisin, a natural antimicrobial peptide with the potential to inhibit growth of
      food spoilage and pathogenic microorganisms such as Listeria monocytogenes. Five
      commercial plastic films with different chemical compositions and surface
      properties were compared in this study: low-density polyethylene, ethylene-vinyl
      acetate copolymer, and three types of ethylene-methacrylic acid copolymers:
      Surlyn 1601, Nucrel 0403, and Nucrel 0903. The films were coated with nisin at a
      concentration of 1000 IU/cm2. Nisin-coated films were stored at room temperature
      (21 degrees C) and at 4 degrees C and analyzed weekly for 12 weeks. Antimicrobial
      activity of the different nisin-coated films against a nisin indicator strain,
      Lactococcus lactis subsp. cremoris ATCC 14365, and against L. monocytogenes ATCC
      19115 was assessed using an inhibition zone assay. Nisin incorporated into the
      films was recovered by a boiling and extraction procedure, and its activity was
      quantified using an agar well diffusion assay. Film type did not have any
      significant effect on the antimicrobial activity of the nisin-coated films (P <
      0.05); all five film types had comparable inhibition zones on both assays. The
      films maintained stable activity for the duration of the study, both at room
      temperature and refrigeration. The results of this study demonstrate that
      commercially available packaging films can be coated with nisin and the resulting
      antimicrobial films can be conveniently stored at room temperature with no
      adverse effect on nisin activity.

PMID- 17536693
TI  - Extraction of nisin from a 2.5% commercial nisin product using methanol and
      ethanol solutions.
AB  - Nisin is a class Ia bacteriocin used widely in the food industry to inhibit a
      number of gram-positive pathogens. Although this peptide exhibits activity
      against many gram-positive bacteria, its effectiveness can vary significantly
      depending upon the food application. Encapsulation is one method that has been
      investigated for improving the activity of nisin. Improvement of the
      encapsulation efficiency of nisin requires purification of the compound, which
      can be accomplished utilizing organic solvents. The objective of this study was
      to use methanol and ethanol solutions to extract and concentrate nisin from a
      commercial preparation containing 2.5% nisin. Commercial nisin was extracted with
      different concentrations of ethanol or methanol in sterile water for up to 8 h.
      Approximately 75% of the nisin activity was recovered with 10 or 50% ethanol
      compared with less than 1% recovery with an ethanol concentration higher than
      90%. Extraction with 10 or 50% methanol was approximately as effective as that
      with lower concentrations of ethanol. However, yields were significantly greater
      for extraction with methanol at concentrations greater than 90%. The solubility
      of the nisin likely influenced the extraction profiles for the conditions used.
      Purification for an 8-h extraction using 10 and 50% ethanol was 1.36 and 1.93
      times, respectively. Purification was less than 0.1 at higher ethanol
      concentrations due to poor extraction. For methanol treatments, purification
      factors were all 1.09 to 5.98, and they increased as methanol concentration
      increased. This method for extracting and purifying nisin from dairy proteins
      using organic solvents may provide an alternative means for preparing and
      concentrating nisin for encapsulation and other applications.

PMID- 17536694
TI  - Minimally processed vegetable salads: microbial quality evaluation.
AB  - The increasing demand for fresh fruits and vegetables and for convenience foods
      is causing an expansion of the market share for minimally processed vegetables.
      Among the more common pathogenic microorganisms that can be transmitted to humans
      by these products are Listeria monocytogenes, Escherichia coli O157:H7, and
      Salmonella. The aim of this study was to evaluate the microbial quality of a
      selection of minimally processed vegetables. A total of 181 samples of minimally
      processed leafy salads were collected from retailers in the city of Sao Paulo,
      Brazil. Counts of total coliforms, fecal coliforms, Enterobacteriaceae,
      psychrotrophic microorganisms, and Salmonella were conducted for 133 samples. L.
      monocytogenes was assessed in 181 samples using the BAX System and by plating the
      enrichment broth onto Palcam and Oxford agars. Suspected Listeria colonies were
      submitted to classical biochemical tests. Populations of psychrotrophic
      microorganisms >10(6) CFU/g were found in 51% of the 133 samples, and
      Enterobacteriaceae populations between 10(5) and 106 CFU/g were found in 42% of
      the samples. Fecal coliform concentrations higher than 10(2) CFU/g (Brazilian
      standard) were found in 97 (73%) of the samples, and Salmonella was detected in 4
      (3%) of the samples. Two of the Salmonella-positive samples had <10(2) CFU/g
      concentrations of fecal coliforms. L. monocytogenes was detected in only 1 (0.6%)
      of the 181 samples examined. This positive sample was simultaneously detected by
      both methods. The other Listeria species identified by plating were L. welshimeri
      (one sample of curly lettuce) and L. innocua (2 samples of watercress). The
      results indicate that minimally processed vegetables had poor microbiological
      quality, and these products could be a vehicle for pathogens such as Salmonella
      and L. monocytogenes.

PMID- 17536695
TI  - Effect of extended storage on microbiological quality, somatic cell count, and
      composition of raw goat milk on a farm.
AB  - Dairy goat herds in the United States generally are small, widely scattered, and
      distant from processing facilities. Unlike the situation for cow milk, it is not
      cost-effective to collect goat milk everyday or every other day. In some areas,
      goat milk is collected only once each week, which is in violation of regulations
      specified in the Pasteurized Milk Ordinance for grade A milk. This study was
      conducted to determine the effect of up to 7 days of refrigerated bulk tank
      storage on composition, somatic cell count (SCC), pH, and microbiological quality
      of goat milk. Duplicate farm bulk tank samples were taken daily after the morning
      milking for seven consecutive days each month during the lactation season.
      Samples were analyzed immediately for all variables except free fatty acids.
      There were no significant changes (P > 0.05) detected in milk fat, protein,
      lactose, nonfat solids, SCC, or pH during extended storage, although significant
      effects of stage of lactation (P < 0.05) were observed. The mean standard plate
      count (SPC) increased to 1.8 x 10(5) CFU/ml after 6 days of storage, exceeding
      the grade A limit (i.e., 1.0 x 10(5) CFU/ml). The mean psychrotrophic bacteria
      count increased steadily to 1.5 x 10(4) CFU/ml after 6 days of storage, whereas
      the mean coliform count was approximately 500 CFU/ml for the first 3 days and
      less than 2500 CFU/ml throughout the 7 days of storage. No significant changes (P
      > 0.05) in the concentrations of free fatty acids, except for butyric and
      caprylic acids, were observed during milk storage. When stored under refrigerated
      and sanitary conditions, goat milk in farm bulk tanks met the grade A criteria
      for both SPC and SCC during 5 days of storage but was of low quality thereafter
      because of the growth of psychrotrophic bacteria.

PMID- 17536696
TI  - An overview of microbial food safety programs in beef, pork, and poultry from
      farm to processing in Canada.
AB  - Canada's vision for the agri-food industry in the 21st century is the
      establishment of a national food safety system employing hazard analysis and
      critical control point (HACCP) principles and microbiological verification tools,
      with traceability throughout the gate-to-plate continuum. Voluntary on-farm food
      safety (OFFS) programs, based in part on HACCP principles, provide producers with
      guidelines for good production practices focused on general hygiene and
      biosecurity. OFFS programs in beef cattle, swine, and poultry are currently being
      evaluated through a national recognition program of the Canadian Food Inspection
      Agency. Mandatory HACCP programs in federal meat facilities include microbial
      testing for generic Escherichia coli to verify effectiveness of the processor's
      dressing procedure, specific testing of ground meat for E. coli O157:H7, with
      zero tolerance for this organism in the tested lot, and Salmonella testing of raw
      products. Health Canada's policy on Listeria monocytogenes divides ready-to-eat
      products into three risk categories, with products previously implicated as the
      source of an outbreak receiving the highest priority for inspection and
      compliance. A national mandatory identification program to track livestock from
      the herd of origin to carcass inspection has been established. Can-Trace, a data
      standard for all food commodities, has been designed to facilitate tracking foods
      from the point of origin to the consumer. Although much work has already been
      done, a coherent national food safety strategy and concerted efforts by all
      stakeholders are needed to realize this vision. Cooperation of many government
      agencies with shared responsibility for food safety and public health will be
      essential.

PMID- 17536697
TI  - Hagfish in the New Zealand fjords are supported by chemoautotrophy of forest
      carbon.
AB  - Forest litter is often considered to be a minor energy source to marine
      communities due to its refractory nature. Large volumes of forest litter are
      deposited in the New Zealand fjords, and likely recycled into available energy by
      microbial activity. In this study we used evidence from stable isotope analyses
      to test whether recycled carbon from chemoautotrophs was an important contributor
      to the diet of hagfish (Eptatretus cirrhatus). We then analyzed fatty acid
      biomarkers from the chemoautotrophic clam Solemya parkinsoni and E. cirrhatus to
      further discriminate the contribution of marine, terrestrial, and
      chemoautotrophic sources. Bulk isotopic signatures of E. cirrhatus varied
      considerably (delta13C, from -29.2 per thousand to -16.7 per thousand; delta15N,
      from -2.8 per thousand to +15.5 per thousand; delta34S, from -21.7 per thousand
      to +16.7 per thousand) and indicated that a significant percentage of organic
      matter (38-51%) originated from chemoautotrophs (delta13C, -31.3 per thousand +/-
      0.1 per thousand [mean +/- SE]; delta15N, -5.7 per thousand +/- 0.2 per thousand;
      delta34S, -32.per thousand +/- 3.8 per thousand). Fatty acid biomarkers were
      depleted in 13C, particularly cis-vaccenic acid (18:1omega7: delta13C, -39.0 per
      thousand) indicating specific microbial origins of carbon. A high proportion of
      forest litter in sediments, coupled with isotopic and fatty acid biomarker
      results, indicates that terrestrial organic matter is a dominant contributor to
      this marine benthic system. This study demonstrates a clear linkage between
      terrestrial and marine ecological processes.

PMID- 17536698
TI  - Resource limitation of bacterial production distorts the temperature dependence
      of oceanic carbon cycling.
AB  - Our view of the effects of temperature on bacterial carbon fluxes in the ocean
      has been confounded by the interplay of resource availability. Using an extensive
      compilation of cell-specific bacterial respiration (BRi) and production (BPi), we
      show that both physiological rates respond to changing temperature in a similar
      manner and follow the predictions of the metabolic theory of ecology. Their
      apparently different temperature dependence under warm, oligotrophic conditions
      is due to strong resource limitation of BP, but not of BRi. Thus, and despite
      previous preconception, bacterial growth efficiency (BGE = BPi/[BPi + BRi]) is
      not directly regulated by temperature, but by the availability of substrates for
      growth. We develop simple equations that can be used for the estimation of
      bacterial community metabolism from temperature, chlorophyll concentration, and
      bacterial abundance. Since bacteria are the greatest living planktonic biomass,
      our results challenge current understanding of how warming and shifts in
      ecosystem trophic state will modify oceanic carbon cycle feedbacks to climate
      change.

PMID- 17536699
TI  - Competition-colonization trade-offs and disturbance effects at multiple scales.
AB  - The competition-colonization trade-off has long been a mechanism explaining
      patterns of species coexistence and diversity in nonequilibrium systems. It forms
      one explanation of the intermediate disturbance hypothesis (IDH) for local
      communities--specifically that diversity should be maximized at intermediate
      disturbance frequencies, yet only a fraction of empirical studies support IDH
      predictions. Similarly, this trade-off is also a powerful explanation of
      coexistence at larger spatial scales. I show, with a microbial experimental
      system, that the diversity-disturbance relationship is dependent on the relative
      distribution of species along this trade-off. Here I show that, when species are
      skewed toward late-successional habits, local diversity declines with
      disturbance. Yet, despite this trait skew, diversity at scales larger than the
      patch appears insensitive to the trade-off distribution. Intermediate disturbance
      frequencies produce the greatest diversity in patch successional stage, thus
      benefiting the maximum number of species at larger scales.

PMID- 17536700
TI  - Maximum species richness at intermediate frequencies of disturbance: consistency
      among levels of productivity.
AB  - Development of a mechanistic understanding and predictions of patterns of
      biodiversity is a central theme in ecology. One of the most influential theories,
      the intermediate disturbance hypothesis (IDH), predicts maximum diversity at
      intermediate levels of disturbance frequency. The dynamic equilibrium model
      (DEM), an extension of the IDH, predicts that the level of productivity
      determines at what frequency of disturbance maximum diversity occurs. To test,
      and contrast, the predictions of these two models, a field experiment on marine
      hard-substratum assemblages was conducted with seven levels of disturbance
      frequency and three levels of nutrient availability. Consistent with the IDH,
      maximum diversity, measured as species richness, was observed at an intermediate
      frequency of disturbance. Despite documented effects on productivity, the
      relationship between disturbance and diversity was not altered by the nutrient
      treatments. Thus, in this system the DEM did not improve the understanding of
      patterns of diversity compared to the IDH. Furthermore, it is suggested that
      careful consideration of measurements and practical definitions of productivity
      in natural assemblages is necessary for a rigorous test of the DEM.

PMID- 17536701
TI  - Effects of nutrients, herbivory, and depth on the macroalgal community in the
      rocky sublittoral.
AB  - We studied the interacting roles of nutrient availability and herbivory in
      determining the macroalgal community in a rocky littoral environment. We
      conducted a factorial field experiment where we manipulated nutrient levels and
      herbivory at two sublittoral depths and measured macroalgal colonization and the
      following young assemblage during the growing season. At the community level,
      grazing reduced algal colonization, though the effect varied with depth and its
      interaction with nutrient availability varied in time. In shallow water, the
      total density of macroalgae increased in response to nutrient enrichment, but the
      ability of grazers to reduce macroalgal density also increased with the nutrient
      enrichment, and thus, the community could not escape from the top-down control.
      In deep water, the algal density was lower, except in July when nutrient
      enrichment caused a very dense algal growth. Grazing at the greater depth, though
      effective, was generally of smaller magnitude, and in July it could not limit
      algal recruitment and growth. Species richness peaked at the intermediate
      nutrient level in deep but not in shallow water during most of the growing
      season. Grazing had no effect on diversity of the algal community at either depth
      and only a minor effect on species richness at the greater depth. Opportunistic
      and ephemeral algae benefited from the nutrient enrichment but were also grazed
      to very low densities. Slowly growing and/or perennial species colonized poorly
      in the nutrient enriched treatments, and depending on the species, either
      suffered or indirectly benefited from herbivory. For all species, effects of
      nutrients on colonization depended on depth; usually both nutrient and herbivory
      effects were more pronounced at the shallow depth. We conclude that grazers are
      able to reduce macroalgae over a large range of nutrient availabilities, up to 12
      fold nutrient enrichment in the current experiment, and that the sublittoral
      depth gradient generates variation in the algal community control exerted by both
      herbivory and nutrient availability. Thus temporal and spatial variability in
      both top-down and bottom-up control and in their interaction, especially along
      the depth gradient, may be crucially important for producer diversity and for the
      successional dynamic in a rocky sublittoral environment.

PMID- 17536702
TI  - Regulation of intertidal food webs by avian predators on New England rocky
      shores.
AB  - Although there is a large body of research on food webs in rocky intertidal
      communities, most of the emphasis has been on the marine benthic components.
      Effects of avian predation on highly mobile predators such as crabs, remains
      practically unstudied in rocky shore ecosystems. The crab, Cancer borealis, is an
      important component of the diet of gulls (Larus marinus, L. argentatus) at the
      Isles of Shoals, Maine, USA. C. borealis prey include the predatory gastropod
      Nucella lapillus L., the herbivore Littorina littorea, and mussels Mytilus edulis
      L. We hypothesized that gulls reduce abundance of C. borealis in the low
      intertidal and shallow subtidal, thereby allowing C. borealis prey to persist in
      high numbers. A study of crab tidal migration showed that C. borealis density
      nearly doubled at high tide compared to low tide; thus, crabs from a large
      subtidal source population migrate into the intertidal zone during high tides and
      either emigrate or are removed by gulls during low tides. Results from a small
      scale (1 m2) predator caging experiment in the low intertidal zone indicated that
      enclosed crabs significantly reduced L. littorea abundance when protected from
      gull predation. In a much larger-scale gull exclusion experiment, densities of C.
      borealis increased significantly during low and high tides in exclosures relative
      to the controls. C. borealis density was inversely correlated with changes in the
      abundance of two mesopredators Carcinus maenas and Nucella lapillus, and with the
      space-occupier M. edulis. There was a similar negative correlation between
      abundance of C. borealis and the change in abundance of the herbivore L.
      littorea, but the trend was not significant. Mortality of tethered L. littorea
      was associated with C. borealis density across sites. However, preferred algae
      did not change in response to L. littorea density during the experiment. Thus, we
      found suggestive, but not conclusive, evidence for a three-level cascade
      involving gulls, crabs, and L. littorea. Our studies strongly suggest that gulls,
      as apex predators, generate three-level trophic cascades in rocky intertidal food
      webs by preventing the highly mobile subtidal predator, C. borealis, from
      establishing substantial populations in the low-mid intertidal zone thereby
      indirectly enhancing densities of two key mesopredators (N. lapillus, Carcinus)
      and blue mussels (M. edulis).

PMID- 17536703
TI  - Contrasting natural experiments confirm competition between House Finches and
      House Sparrows.
AB  - After House Finches were introduced from the western to the eastern United States
      and rapidly increased in numbers, House Sparrows declined, leading to suggestions
      that the decline was caused by interspecific competition. However, other
      potential causes were not excluded. The rapid decline in House Finches following
      the emergence of a new disease (mycoplasmal conjunctivitis) caused by a novel
      strain of Mycoplasma gallisepticum (MG) in 1994 has provided a natural experiment
      and an opportunity to revisit the hypothesis that interspecific competition from
      House Finches drives population changes in House Sparrows. If true, the recent
      decline in House Finches should lead to an increase in House Sparrows. In this
      paper we test the hypothesis that House Sparrow and House Finch numbers in the
      northeastern United States vary inversely by examining data from three
      independent volunteer programs that monitor bird species' abundance and
      distribution (Christmas Bird Count, Project FeederWatch, and Breeding Bird
      Survey). In the first analysis we found that House Sparrow and House Finch
      numbers varied inversely during a time interval when House Finches were
      increasing and a time interval when House Finches were decreasing. In the second
      analysis, we found that the rates of geometric change in House Sparrow abundance
      (ln[HOSP(t+1)/HOSP(t)]) were negatively correlated with initial House Finch
      (HOFI(t)) and sparrow (HOSP(t)) abundances at individual sites, irrespective of
      the time period. Given that finch range expansion and subsequent declines in
      abundance are the result of two very different phenomena, it would be very
      unlikely for apparent competition or spurious correlations to cause the observed
      concomitant changes in House Sparrow abundance. We conclude that interspecific
      competition exists between these two species.

PMID- 17536704
TI  - Malaria and risk of predation: a comparative study of birds.
AB  - Predators have been hypothesized to prey on individuals in a poor state of
      health, although this hypothesis has only rarely been examined. We used extensive
      data on prey abundance and availability from two long-term studies of the
      European Sparrowhawk (Accipiter nisus) and the Eurasian Goshawk (Accipiter
      gentilis) to quantify the relationship between predation risk of different prey
      species and infection with malaria and other protozoan blood parasites. Using a
      total of 31 745 prey individuals of 65 species of birds from 1709 nests during
      1977-1997 for the Sparrowhawk and a total of 21 818 prey individuals of 76
      species of birds from 1480 nests for the Goshawk during 1977-2004, we show that
      prey species with a high prevalence of blood parasites had higher risks of
      predation than species with a low prevalence. That was also the case when a
      number of confounding variables of prey species, such as body mass, breeding
      sociality, sexual dichromatism, and similarity among species in risk of predation
      due to common descent, were controlled in comparative analyses of standardized
      linear contrasts. Prevalence of the genera Haemoproteus, Leucocytozoon,
      Plasmodium, and Trypanosoma were correlated with each other, and we partitioned
      out the independent effects of different protozoan genera on predation risk in
      comparative analyses. Prevalence of Haemoproteus, Leucocytozoon, and Plasmodium
      accounted for interspecific variation in predation risk for the two raptors.
      These findings suggest that predation is an important factor affecting parasite
      host dynamics because predators tend to prey on hosts that are more likely to be
      infected, thereby reducing the transmission success of parasites. Furthermore,
      this study demonstrates that protozoan infections are a common cause of death for
      hosts mediated by increased risk of predation.

PMID- 17536705
TI  - Increased sedentariness in European Blackbirds following urbanization: a
      consequence of local adaptation?
AB  - Urbanization changes local environmental conditions and may lead to altered
      selection regimes for life history traits of organisms thriving in cities.
      Previous studies have reported changes in breeding phenology and even trends
      toward increased sedentariness in migratory bird species colonizing urban areas.
      However, does the change in migratory propensity simply represent a phenotypic
      adjustment to local urban environment, or is it genetically based and hence the
      result of local adaptation? To test this, we hand-raised European Blackbirds
      (Turdus merula) from urban and forest populations, quantified their nocturnal
      activity and fat deposition covering two complete migratory cycles and examined
      the consequences of a reduced migratory propensity for the timing of gonadal
      development (a physiological measure of the seasonal timing of reproduction).
      Although nocturnal activities differed strikingly between fall and spring
      seasons, with low activities during the fall and high activities during the
      spring seasons, our data confirm, even in birds kept from early life under common
      garden conditions, a change toward reduced migratoriness in urban blackbirds. The
      first score of a principal component analysis including amount of nocturnal
      activity and fat deposition, defined as migratory disposition, was lower in urban
      than in forest males particularly during their first year, whereas females did
      not differ. The results suggest that the intrinsic but male-biased difference is
      genetically determined, although early developmental effects cannot be excluded.
      Moreover, individuals with low migratory disposition developed their gonads
      earlier, resulting in longer reproductive seasons. Since urban conditions
      facilitate earlier breeding, intrinsic shifts to sedentariness thus seem to be
      adaptive in urban habitats. These results corroborate the idea that urbanization
      has evolutionary consequences for life history traits such as migratory behavior.

PMID- 17536706
TI  - Iteroparity in the variable environment of the salamander Ambystoma tigrinum.
AB  - Simultaneous estimation of survival, reproduction, and movement is essential to
      understanding how species maximize lifetime reproduction in environments that
      vary across space and time. We conducted a four-year, capture-recapture study of
      three populations of eastern tiger salamanders (Ambystoma tigrinum tigrinum) and
      used multistate mark-recapture statistical methods to estimate the manner in
      which movement, survival, and breeding probabilities vary under different
      environmental conditions across years and among populations and habitats. We
      inferred how individuals may mitigate risks of mortality and reproductive failure
      by deferring breeding or by moving among populations. Movement probabilities
      among populations were extremely low despite high spatiotemporal variation in
      reproductive success and survival, suggesting possible costs to movements among
      breeding ponds. Breeding probabilities varied between wet and dry years and
      according to whether or not breeding was attempted in the previous year.
      Estimates of survival in the nonbreeding, forest habitat varied among populations
      but were consistent across time. Survival in breeding ponds was generally high in
      years with average or high precipitation, except for males in an especially
      ephemeral pond. A drought year incurred severe survival costs in all ponds to
      animals that attempted breeding. Female salamanders appear to defer these
      episodic survival costs of breeding by choosing not to breed in years when the
      risk of adult mortality is high. Using stochastic simulations of survival and
      breeding under historical climate conditions, we found that an interaction
      between breeding probabilities and mortality limits the probability of multiple
      breeding attempts differently between the sexes and among populations.

PMID- 17536707
TI  - Regulation of benthic algal and animal communities by salt marsh plants: impact
      of shading.
AB  - Plant cover is a fundamental feature of many coastal marine and terrestrial
      systems and controls the structure of associated animal communities. Both natural
      and human-mediated changes in plant cover influence abiotic sediment properties
      and thus have cascading impacts on the biotic community. Using clipping
      (structural) and light (shading) manipulations in two salt marsh vegetation zones
      (one dominated by Spartina foliosa and one by Salicornia virginica), we tested
      whether these plant species exert influence on abiotic environmental factors and
      examined the mechanisms by which these changes regulate the biotic community. In
      an unshaded (plant and shade removal) treatment, marsh soils exhibited harsher
      physical properties, a microalgal community composition shift toward increased
      diatom dominance, and altered macrofaunal community composition with lower
      species richness, a larger proportion of insect larvae, and a smaller proportion
      of annelids, crustaceans, and oligochaetes compared to shaded (plant removal,
      shade mimic) and control treatment plots. Overall, the shaded treatment plots
      were similar to the controls. Plant cover removal also resulted in parallel
      shifts in microalgal and macrofaunal isotopic signatures of the most dynamic
      species. This suggests that animal responses are seen mainly among microalgae
      grazers and may be mediated by plant modification of microalgae. Results of these
      experiments demonstrate how light reduction by the vascular plant canopy can
      control salt marsh sediment communities in an arid climate. This research
      facilitates understanding of sequential consequences of changing salt marsh plant
      cover associated with climate or sea level change, habitat degradation, marsh
      restoration, or plant invasion.

PMID- 17536708
TI  - Life history and viability of a long-lived marine invertebrate: the octocoral
      Paramuricea clavata.
AB  - The red gorgonian Paramuricea clavata is a long-lived, slow-growing sessile
      invertebrate of ecological and conservation importance in the northwestern
      Mediterranean Sea. We develop a series of size-based matrix models for two
      Paramuricea clavata populations. These models were used to estimate basic life
      history traits for this species and to evaluate the viability of the red
      gorgonian populations we studied. As for many other slow-growing species,
      sensitivity and elasticity analysis demonstrate that gorgonian population growth
      is far more sensitive to changes in survival rates than to growth, shrinkage, or
      reproductive rates. The slow growth and low mortality of red gorgonians results
      in low damping ratios, indicating slow convergence to stable size structures (at
      least 50 years). The stable distributions predicted by the model did not differ
      from the observed ones. However, our simulations point out the fragility of this
      species, showing both populations in decline and high risk of extinction over
      moderate time horizons. These declines appear to be related to a recent increase
      in anthropogenic disturbances. Relative to their life span, the values of
      recruitment elasticity for Paramuricea clavata are lower than those reported for
      other marine organisms but are similar to those reported for some long-lived
      plants. These values and the delayed age of sexual maturity, in combination with
      the longevity of the species, show a clear fecundity/mortality trade-off. Full
      demographic studies of sessile marine species are quite scarce but can provide
      insight into population dynamics and life history patterns for these difficult
      and under-studied species. While our work shows clear results for the red
      gorgonian, the variability in some of our estimates suggest that future work
      should include data collection over longer temporal and spatial scales to better
      understand the long-term effects of natural and anthropogenic disturbances on red
      gorgonian populations.

PMID- 17536709
TI  - Effects of species diversity on community biomass production change over the
      course of succession.
AB  - Over the past decade an increasing number of studies have experimentally
      manipulated the number of species in a community and examined how this alters the
      aggregate production of species biomass. Many of these studies have shown that
      the effects of richness on biomass change through time, but we have limited
      understanding of the mechanisms that produce these dynamic trends. Here we report
      the results of an experiment in which we manipulated the richness of freshwater
      algae in laboratory microcosms. We used two experimental designs (additive and
      substitutive) that make different assumptions about how patches are initially
      colonized, and then tracked the development of community biomass from the point
      of initial colonization through a period of 6-12 generations of the focal
      species. We found that the effect of initial species richness on biomass
      production qualitatively shifted twice over the course of the experiment. The
      first shift occurred as species transitioned from density-independent to
      dependent phases of population growth. At this time, intraspecific competition
      caused monocultures to approach their respective carrying capacities more slowly
      than polycultures. As a consequence, species tended to over-yield for a brief
      time, generating a positive, but transient effect of diversity on community
      biomass. The second shift occurred as communities approached carrying capacity.
      At this time, strong interspecific interactions caused biomass to be dominated by
      the competitively superior species in polycultures. As this species had the
      lowest carrying capacity, a negative effect of diversity on biomass resulted in
      late succession. Although these two shifts produced dynamics that appeared
      complex, we show that the patterns can be fit to a simple Lotka-Volterra model of
      competition. Our results suggest that the effects of algal diversity on primary
      production change in a predictable sequence through successional time.

PMID- 17536710
TI  - Climate, hydrologic disturbance, and succession: drivers of floodplain pattern.
AB  - Floodplains are among the world's most threatened ecosystems due to the
      pervasiveness of dams, levee systems, and other modifications to rivers. Few
      unaltered floodplains remain where we may examine their dynamics over decadal
      time scales. Our study provides a detailed examination of landscape change over a
      60-year period (1945-2004) on the Nyack floodplain of the Middle Fork of the
      Flathead River, a free-flowing, gravel-bed river in northwest Montana, USA. We
      used historical aerial photographs and airborne and satellite imagery to
      delineate habitats (i.e., mature forest, regenerative forest, water, cobble)
      within the floodplain. We related changes in the distribution and size of these
      habitats to hydrologic disturbance and regional climate. Results show a
      relationship between changes in floodplain habitats and annual flood magnitude,
      as well as between hydrology and the cooling and warming phases of the Pacific
      Decadal Oscillation (PDO). Large magnitude floods and greater frequency of
      moderate floods were associated with the cooling phases of the PDO, resulting in
      a floodplain environment dominated by extensive restructuring and regeneration of
      floodplain habitats. Conversely, warming phases of the PDO corresponded with
      decreases in magnitude, duration, and frequency of critical flows, creating a
      floodplain environment dominated by late successional vegetation and low levels
      of physical restructuring. Over the 60-year time series, habitat change was
      widespread throughout the floodplain, though the relative abundances of the
      habitats did not change greatly. We conclude that the long- and short-term
      interactions of climate, floods, and plant succession produce a shifting habitat
      mosaic that is a fundamental attribute of natural floodplain ecosystems.

PMID- 17536711
TI  - Dominant species identity, not community evenness, regulates invasion in
      experimental grassland plant communities.
AB  - While there has been extensive interest in understanding the relationship between
      diversity and invasibility of communities, most studies have only focused on one
      component of diversity: species richness. Although the number of species can
      affect community invasibility, other aspects of diversity, including species
      identity and community evenness, may be equally important. While several field
      studies have examined how invasibility varies with diversity by manipulating
      species identity or evenness, the results are often confounded by resource
      heterogeneity, site history, or disturbance. We designed a mesocosm experiment to
      examine explicitly the role of dominant species identity and evenness on the
      invasibility of grassland plant communities. We found that the identity of the
      dominant plant species, but not community evenness, significantly impacted
      invasibility. Using path analysis, we found that community composition (dominant
      species identity) reduced invasion by reducing early-season light availability
      and increasing late-season plant community biomass. Nitrogen availability was an
      important factor for the survival of invaders in the second year of the
      experiment. We also found significant direct effects of certain dominant species
      on invasion, although the mechanisms driving these effects remain unclear. The
      magnitude of dominant species effects on invasibility we observed are comparable
      to species richness effects observed in other studies, showing that species
      composition and dominant species can have strong effects on the invasibility of a
      community.

PMID- 17536712
TI  - Importance of species traits for species distribution in fragmented landscapes.
AB  - Knowledge of the relationship between species traits and species distribution in
      fragmented landscapes is important for understanding current distribution
      patterns and as background information for predictive models of the effect of
      future landscape changes. The existing studies on the topic suffer from several
      drawbacks. First, they usually consider only traits related to dispersal ability
      and not growth. Furthermore, they do not apply phylogenetic corrections, and we
      thus do not know how considerations of phylogenetic relationships can alter the
      conclusions. Finally, they usually apply only one technique to calculate habitat
      isolation, and we do not know how other isolation measures would change the
      results. We studied the issues using 30 species forming congeneric pairs
      occurring in fragmented dry grasslands. We measured traits related to dispersal,
      survival, and growth in the species and recorded distribution of the species in
      215 grassland fragments. We show many strong relationships between species traits
      related to both dispersal and growth and species distribution in the landscape,
      such as the positive relationship between habitat occupancy and anemochory and
      negative relationships between habitat occupancy and seed dormancy. The
      directions of these relationships, however, often change after application of
      phylogenetic correction. For example, more isolated habitats host species with
      smaller seeds. After phylogenetic correction, however, they turn out to host
      species with larger seeds. The conclusions also partly change depending on how we
      calculate habitat isolation. Specifically, habitat isolation calculated from
      occupied habitats only has the highest predictive power. This indicates slow
      dynamics of the species. All the results support the expectation that species
      traits have a high potential to explain patterns of species distribution in the
      landscape and that they can be used to build predictive models of species
      distribution. The specific conclusions are, however, dependent on the technique
      used, and we should carefully consider this when comparing among different
      studies. Since different techniques answer slightly different questions, we
      should attempt to use analyses both with and without phylogenetic correction and
      explore different isolation measures whenever possible and compare the results.

PMID- 17536713
TI  - Soil feedback of exotic savanna grass relates to pathogen absence and mycorrhizal
      selectivity.
AB  - Enemy release of exotic plants from soil pathogens has been tested by examining
      plant-soil feedback effects in repetitive growth cycles. However, positive soil
      feedback may also be due to enhanced benefit from the local arbuscular
      mycorrhizal fungi (AMF). Few studies actually have tested pathogen effects, and
      none of them did so in arid savannas. In the Kalahari savanna in Botswana, we
      compared the soil feedback of the exotic grass Cenchrus biflorus with that of two
      dominant native grasses, Eragrostis lehmanniana and Aristida meridionalis. The
      exotic grass had neutral to positive soil feedback, whereas both native grasses
      showed neutral to negative feedback effects. Isolation and testing of root
      inhabiting fungi of E. lehmanniana yielded two host-specific pathogens that did
      not influence the exotic C. biflorus or the other native grass, A. meridionalis.
      None of the grasses was affected by the fungi that were isolated from the roots
      of the exotic C. biflorus. We isolated and compared the AMF community of the
      native and exotic grasses by polymerase chain reaction-denaturing gradient gel
      elecrophoresis (PCR-DGGE), targeting AMF 18S rRNA. We used roots from
      monospecific field stands and from plants grown in pots with mixtures of soils
      from the monospecific field stands. Three-quarters of the root samples of the
      exotic grass had two nearly identical sequences, showing 99% similarity with
      Glomus versiforme. The two native grasses were also associated with distinct
      bands, but each of these bands occurred in only a fraction of the root samples.
      The native grasses contained a higher diversity of AMF bands than the exotic
      grass. Canonical correspondence analyses of the AMF band patterns revealed almost
      as much difference between the native and exotic grasses as between the native
      grasses. In conclusion, our results support the hypothesis that release from soil
      borne enemies may facilitate local abundance of exotic plants, and we provide the
      first evidence that these processes may occur in arid savanna ecosystems.
      Pathogenicity tests implicated the involvement of soil pathogens in the soil
      feedback responses, and further studies should reveal the functional consequences
      of the observed high infection with a low diversity of AMF in the roots of exotic
      plants.

PMID- 17536714
TI  - Preferences for different nitrogen forms by coexisting plant species and soil
      microbes.
AB  - The growing awareness that plants might use a variety of nitrogen (N) forms, both
      organic and inorganic, has raised questions about the role of resource
      partitioning in plant communities. It has been proposed that coexisting plant
      species might be able to partition a limited N pool, thereby avoiding competition
      for resources, through the uptake of different chemical forms of N. In this
      study, we used in situ stable isotope labeling techniques to assess whether
      coexisting plant species of a temperate grassland (England, UK) display
      preferences for different chemical forms of N, including inorganic N and a range
      of amino acids of varying complexity. We also tested whether plants and soil
      microbes differ in their preference for different N forms, thereby relaxing
      competition for this limiting resource. We examined preferential uptake of a
      range of 13C15N-labeled amino acids (glycine, serine, and phenylalanine) and 15N
      labeled inorganic N by coexisting grass species and soil microbes in the field.
      Our data show that while coexisting plant species simultaneously take up a
      variety of N forms, including inorganic N and amino acids, they all showed a
      preference for inorganic N over organic N and for simple over the more complex
      amino acids. Soil microbes outcompeted plants for added N after 50 hours, but in
      the long-term (33 days) the proportion of added 15N contained in the plant pool
      increased for all N forms except for phenylalanine, while the proportion in the
      microbial biomass declined relative to the first harvest. These findings suggest
      that in the longer-term plants become more effective competitors for added 15N.
      This might be due to microbial turnover releasing 15N back into the plant-soil
      system or to the mineralization and subsequent plant uptake of 15N transferred
      initially to the organic matter pool. We found no evidence that soil microbes
      preferentially utilize any of the N forms added, despite previous studies showing
      that microbial preferences for N forms vary over time. Our data suggest that
      coexisting plants can outcompete microbes for a variety of N forms, but that such
      plant species show similar preferences for inorganic over organic N.

PMID- 17536715
TI  - Carbohydrate storage and light requirements of tropical moist and dry forest tree
      species.
AB  - In many plant communities, there is a negative interspecific correlation between
      relative growth rates and survival of juveniles. This negative correlation is
      most likely caused by a trade-off between carbon allocation to growth vs.
      allocation to defense and storage. Nonstructural carbohydrates (NSC) stored in
      stems allow plants to overcome periods of stress and should enhance survival. In
      order to assess how species differ in carbohydrate storage in relation to
      juvenile light requirements, growth, and survival, we quantified NSC
      concentrations and pool sizes in sapling stems of 85 woody species in moist semi
      evergreen and dry deciduous tropical forests in the rainy season in Bolivia.
      Moist forest species averaged higher NSC concentrations than dry forest species.
      Carbohydrate concentrations and pool sizes decreased with the light requirements
      of juveniles of the species in the moist forest but not in the dry forest.
      Combined, these results suggest that storage is especially important for species
      that regenerate in persistently shady habitats, as in the understory of moist
      evergreen forests. For moist forest species, sapling survival rates increased
      with NSC concentrations and pool sizes while growth rates declined with the NSC
      concentrations and pool sizes. No relationships were found for dry forest
      species. Carbon allocation to storage contributes to the growth-survival trade
      off through its positive effect on survival. And, a continuum in carbon storage
      strategies contributes to a continuum in light requirements among species. The
      link between storage and light requirements is especially strong in moist
      evergreen forest where species sort out along a light gradient, but disappears in
      dry deciduous forest where light is a less limiting resource and species sort out
      along drought and fire gradients.

PMID- 17536716
TI  - Fitness related diet-mixing by intraspecific host-plant-switching of specialist
      insect herbivores.
AB  - Generalist insect herbivores may profit by feeding on a mixture of plant species
      that differ in nutritional quality. Herbivore performance can also be affected by
      intraspecific host plant variation. However, it is unknown whether conspecific
      plant individuals differ sufficiently to promote diet-mixing behavior in
      specialist herbivores. We experimentally tested this "specialist diet-mixing
      hypothesis" for specialist caterpillars (Chrysopsyche imparilis, Lasiocampidae)
      in a West African savanna. The caterpillars switched regularly between host tree
      individuals (Combretum fragrans, Combretaceae). To examine whether switching
      benefited caterpillar performance via diet-mixing, the caterpillars were reared
      either on leaves from several plant individuals (mixed diet) or on leaves from a
      single plant. The strongest effect of diet-mixing was found for fecundity, with
      females reared on a mixed diet laying significantly more eggs than sisters
      receiving a single-plant diet. In addition, a mixed diet decreased variability in
      egg size and increased the growth of second-instar caterpillars. Supplementary
      food choice experiments were conducted to assess a potential influence of lowered
      host quality (induced by herbivory) on caterpillar behavior; no such effect was
      found. By linking intraspecific host-switching behavior and herbivore
      performance, this study provides new information on the relevance of
      intraspecific plant variation for herbivorous insects.

PMID- 17536717
TI  - Direct and interactive effects of enemies and mutualists on plant performance: a
      meta-analysis.
AB  - Plants engage in multiple, simultaneous interactions with other species; some
      (enemies) reduce and others (mutualists) enhance plant performance. Moreover,
      effects of different species may not be independent of one another; for example,
      enemies may compete, reducing their negative impact on a plant. The magnitudes of
      positive and negative effects, as well as the frequency of interactive effects
      and whether they tend to enhance or depress plant performance, have never been
      comprehensively assessed across the many published studies on plant-enemy and
      plant-mutualist interactions. We performed a meta-analysis of experiments in
      which two enemies, two mutualists, or an enemy and a mutualist were manipulated
      factorially. Specifically, we performed a factorial meta-analysis using the log
      response ratio. We found that the magnitude of (negative) enemy effects was
      greater than that of (positive) mutualist effects in isolation, but in the
      presence of other species, the two effects were of comparable magnitude. Hence
      studies evaluating single-species effects of mutualists may underestimate the
      true effects found in natural settings, where multiple interactions are the norm
      and indirect effects are possible. Enemies did not on average influence the
      effects on plant performance of other enemies, nor did mutualists influence the
      effects of mutualists. However, these averages mask significant and large, but
      positive or negative, interactions in individual studies. In contrast, mutualists
      ameliorated the negative effects of enemies in a manner that benefited plants;
      this overall effect was driven by interactions between pathogens and belowground
      mutualists (bacteria and mycorrhizal fungi). The high frequency of significant
      interactive effects suggests a widespread potential for diffuse rather than
      pairwise coevolutionary interactions between plants and their enemies and
      mutualists. Pollinators and mycorrhizal fungi enhanced plant performance more
      than did bacterial mutualists. In the greenhouse (but not the field), pathogens
      reduced plant performance more than did herbivores, pathogens were more damaging
      to herbaceous than to woody plants, and herbivores were more damaging to crop
      than to non-crop plants (suggesting evolutionary change in plants or herbivores
      following crop domestication). We discuss how observed differences in effect size
      might be confounded with methodological differences among studies.

PMID- 17536718
TI  - Predator-induced morphological defenses in marine zooplankton: a larval case
      study.
AB  - While there are numerous reports of predator-induced morphological defenses for
      freshwater zooplankton, freshwater larvae, and benthic marine animals, a
      literature search revealed no reports of predator-induced morphological defenses
      for marine zooplankton. Rarity of predator-induced morphological defenses in
      marine zooplankton would imply a difference in predation risks compared to those
      experienced by freshwater organisms and benthic marine adults, whereas the
      presence of such plasticity in defenses would imply that risks are modified by
      developmental responses. This study reports a predator-induced change in defenses
      and vulnerability of a marine planktonic larva. Specifically, when reared in the
      presence of zoea larvae of Cancer spp., veliger larvae of the intertidal snail
      Littorina scutulata developed significantly smaller shell apertures and rounder
      shells than did cohort veligers reared in the absence of predator cues. Pairwise
      predation trials demonstrated that veligers reared with caged zoeas throughout
      development had greater survival than predator-naive veligers during short-term
      exposure to zoeas. The development of predator-induced morphological defenses by
      some marine larvae introduces a range of testable hypotheses on developmental
      plasticity that reduces vulnerability of planktonic larvae and other marine
      zooplankton to predators.

PMID- 17536719
TI  - Effects of river otter activity on terrestrial plants in trophically altered
      Yellowstone Lake.
AB  - Animals that deposit aquatically derived nutrients on terrestrial landscapes link
      food webs and affect a variety of in situ processes. This phenomenon, however, is
      poorly documented in freshwater habitats, especially where species introductions
      have drastically changed an ecosystem's trophic structure. In this study, we used
      stable isotopes to document water-to-land nutrient transport by river otters
      (Lontra canadensis) around Yellowstone Lake, an ecosystem recently altered by
      nonnative species invasions. We then investigated the effects of otter
      fertilization on plant growth and prevalence at latrine (scent-marking) sites and
      evaluated how the recent changes to the lake's food web could influence these
      plant responses. Values of delta15N were higher on latrines compared to non
      latrine sites in five of seven sample plant taxa. Additionally, latrine grasses
      had higher percentage N than those from non-latrines. Foliar delta15N positively
      related to fecal deposition rate for some plants, indicating that increased otter
      scent-marking led to a rise in these N values. Logistic regression models
      indicated that otters selected for well-shaded latrines with access to foraging.
      Atypical latrines, misclassified as non-latrines by the regression models, had
      values of delta15N similar to correctly classified latrines, suggesting that site
      effects alone cannot explain elevated N values at otter latrine sites. No
      difference in plant diversity or percent cover of N-fixing taxa occurred between
      latrine and nonlatrine sites, though specific genera did differ between site
      types. Measurements of shoot lengths indicated increased growth of some latrine
      currants (Ribes sp.). In Yellowstone Lake, a twofold reduction in otter numbers
      could result in an even greater decline in nutrient deposition at latrines, as
      otters may become less social in a system with decreased prey availability. Our
      results highlight the role of animals in linking aquatic and terrestrial habitats
      in inland freshwater systems and suggest that ongoing changes in the trophic
      structure of Yellowstone Lake could have unexpected ramifications well beyond the
      lake itself.

PMID- 17536720
TI  - Dune vegetation fertilization by nesting sea turtles.
AB  - Sea turtle nesting presents a potential pathway to subsidize nutrient-poor dune
      ecosystems, which provide the nesting habitat for sea turtles. To assess whether
      this positive feedback between dune plants and turtle nests exists, we measured N
      concentration and delta15N values in dune soils, leaves from a common dune plant
      (sea oats [Uniola paniculata]), and addled eggs of loggerhead (Caretta caretta)
      and green turtles (Chelonia mydas) across a nesting gradient (200-1050 nests/km)
      along a 40.5-km stretch of beach in east central Florida, USA. The delta15N
      levels were higher in loggerhead than green turtle eggs, denoting the higher
      trophic level of loggerhead turtles. Soil N concentration and delta15N values
      were both positively correlated to turtle nest density. Sea oat leaf tissue
      delta15N was also positively correlated to nest density, indicating an increased
      use of augmented marine-based nutrient sources. Foliar N concentration was
      correlated with delta15N, suggesting that increased nutrient availability from
      this biogenic vector may enhance the vigor of dune vegetation, promoting dune
      stabilization and preserving sea turtle nesting habitat.

PMID- 17536721
TI  - Kernel density estimators of home range: smoothing and the autocorrelation red
      herring.
AB  - Two oft-cited drawbacks of kernel density estimators (KDEs) of home range are
      their sensitivity to the choice of smoothing parameter(s) and their need for
      independent data. Several simulation studies have been conducted to compare the
      performance of objective, data-based methods of choosing optimal smoothing
      parameters in the context of home range and utilization distribution (UD)
      estimation. Lost in this discussion of choice of smoothing parameters is the
      general role of smoothing in data analysis, namely, that smoothing serves to
      increase precision at the cost of increased bias. A primary goal of this paper is
      to illustrate this bias-variance trade-off by applying KDEs to sampled locations
      from simulated movement paths. These simulations will also be used to explore the
      role of autocorrelation in estimating UDs. Autocorrelation can be reduced (1) by
      increasing study duration (for a fixed sample size) or (2) by decreasing the
      sampling rate. While the first option will often be reasonable, for a fixed study
      duration higher sampling rates should always result in improved estimates of
      space use. Further, KDEs with typical data-based methods of choosing smoothing
      parameters should provide competitive estimates of space use for fixed study
      periods unless autocorrelation substantially alters the optimal level of
      smoothing.

PMID- 17536722
TI  - Recent developments and contributions from Chinese scientists in multidimensional
      separations for proteomics and traditional Chinese medicines.
AB  - The most basic task in proteomics remains the detection and identification of
      proteins from a biological sample, and the most traditional way to achieve this
      goal consists in protein separations performed by two-dimensional polyacrylamide
      gel electrophoresis (2-D PAGE). Yet the 2-D PAGE-mass spectrometry (MS) approach
      has its drawbacks with regard to automation, sensitivity, and throughput.
      Consequently, considerable effort has been devoted to the development of non-gel
      based proteome separation technologies in an effort to alleviate the shortcomings
      of 2-D PAGE. In addition, traditional Chinese medicines (TCMs), due to their long
      period of clinical testing and reliable therapeutic efficacy, are attracting
      increased global attention. However, hundreds or even thousands of components are
      usually present in TCMs, which results in great difficulties of separation. As a
      mainstream separation tool, multidimensional liquid separation systems have shown
      powerful separation ability, high peak capacity, and excellent detectability in
      the analysis of complex samples including biological samples and TCMs, etc.
      Therefore, this review emphasizes the most recent advances in multidimensional
      liquid chromatography and capillary electrophoresis-based separation techniques,
      and the corresponding applications in proteomics and TCMs. In view of the
      significant contributions from Chinese scientists, this review focuses mainly on
      the work of Chinese scientists in the above fields.

PMID- 17536723
TI  - Recent development of monolithic materials as matrices in microcolumn separation
      systems.
AB  - This review summarizes the development of monolithic materials, including both
      organic and inorganic polymers, according mainly to the papers published in the
      past two years. Due to their good permeability, fast mass transfer, high
      stability, and their ease of modification, such materials have been widely used
      in microcolumn separation systems, not only as stationary phases for CEC and
      capillary HPLC, but also as substances for sample concentration and enzyme
      reactor. All the research results demonstrate that monolithic materials in
      microseparation systems can be expected to play an increasingly important role in
      the analysis of complex samples.

PMID- 17536724
TI  - Synthesis and chromatographic properties of a chiral stationary phase derived
      from bovine serum albumin immobilized on magnesia-zirconia using phosphonate
      spacers.
AB  - A novel bovine serum albumin (BSA)-modified magnesia-zirconia stationary phase
      was prepared using the sodium salt of cis-(3-methyloxiranyl)phosphonic acid
      (fosfomycin) as spacer and glutaraldehyde as coupler. Baseline separation of six
      derivatized amino acids (DNB-Leu, Dansyl-Val, etc.) was achieved on this column
      using ammonium acetate buffer-isopropanol mobile phase at a flow rate of 1.0
      mL/min. The effects of mobile phase composition, eluent pH value, column
      temperature, and flow rate on the retention and separation of chiral compounds
      were also investigated. The BSA chiral stationary phase (BSA-CSP) was relatively
      stable under experimental conditions. The coupling reaction in this method was
      mild, reliable, and reproducible; thus it was also suitable for the
      immobilization of various biopolymers with amino groups in the preparation of
      chromatography stationary phases.

PMID- 17536725
TI  - Chemical fingerprint and quantitative analysis of fructus psoraleae by high
      performance liquid chromatography.
AB  - Fructus Psoraleae, a widely used traditional Chinese medicine, is well known as a
      health supplement ingredient. In our study, an improved and comprehensive HPLC
      fingerprint of Fructus Psoraleae was established. Two important new benzofuran
      glycosides, psoralenoside and isopsoralenoside, were identified as characteristic
      constituents for the first time. HPLC separation was performed on an RP-C8
      column. The mobile phase was acetonitrile and 0.1% acetic acid solution with
      linear gradient change of acetonitrile from 10 to 82% in 40 min. The flow rate
      was 1.0 mL/min, and the detection wavelength was set at 310 nm. The HPLC
      chromatograms of twenty-six samples from different regions of China showed a
      similar pattern. Twelve peaks were selected as characteristic peaks and further
      identified as psoralenoside, isopsoralenoside, psoralen, isopsoralen,
      bavachromene, corylifolin, corylin, psoralidin, isobavachalcone, bavachinin,
      corylifol A, and bakuchiol, respectively. Nine of them were simultaneously
      quantitatively analyzed for the first time. A more comprehensive analytical
      method was established for the fingerprint of Fructus Psoraleae. It is very
      useful for authentication and quality assessment of the crude drug.

PMID- 17536726
TI  - Development of microwave assisted extraction for the simultaneous determination
      of isoflavonoids and saponins in radix astragali by high performance liquid
      chromatography.
AB  - A microwave assisted extraction (MAE) procedure was first developed for the
      simultaneous determination of isoflavonoids and astragalosides in Radix Astragali
      (RA). MAE showed the highest extraction efficiency when compared to Soxhlet,
      reflux, and ultrasonic extraction. It was found that flavonoid glycoside
      malonates were converted into their related glycosides during the prolonged
      conventional extraction, thus affecting the reproducibility. However, the
      conversion was inhibited when using MAE. After being optimized in terms of
      solvents, microwave power, and irradiation time, MAE was used for the
      simultaneous determination of isoflavonoids and astragalosides in RA with HPLC-UV
      evaporative light scattering detection (ELSD). Our results indicated that
      extraction by MAE was more effective than by other conventional techniques.
      Moreover, the MAE method followed by HPLC-UV-ELSD determination was a simple,
      rapid, and reliable method for the quality assessment of RA.

PMID- 17536727
TI  - Chemical characteristics of three medicinal plants of the Panax genus determined
      by HPLC-ELSD.
AB  - The morphological appearance and main ingredients of three Chinese medicines
      (CMs), P. ginseng, P. quinquefolius, and P. notoginseng of the Panax genus, are
      similar. However, their pharmacological activities are obviously different. To
      ensure their safety and efficacy, chemical characteristics of the three CMs were
      determined using pressurized liquid extraction and HPLC-evaporative light
      scattering detection. Twelve major saponins, namely notoginsenoside R1, pseudo
      ginsenoside F11, ginsenosides Rg1, Re, Rf, Rb1, Rg2, Rc, Rb2, Rb3, Rd, and Rg3
      were also quantitatively compared among the three CMs. The contents of total
      investigated saponins varied considerably, by up to 4-14-fold, between the
      highest (P. notoginseng, 82.8-136.5 mg/g) and the lowest values (P. ginseng, 10.0
      21.1 mg/g). Hierarchical clustering analysis based on the characteristics of 11
      investigated saponins (except ginsenoside Rb3) and notoginsenoside R1, pseudo
      ginsenoside F11, and the ratio of ginsenoside Rg1/Rb1 and Rg1/Re showed that 56
      tested samples were divided into three main clusters in accordance with the three
      Panax species. Similarity evaluation of chromatograms was also performed using
      "Similarity Evaluation System for Chromatographic Fingerprint of Traditional
      Chinese Medicine (Version 2004A)". The results showed that a high degree of
      similarity existed within individual clusters, but a low degree between the
      clusters, which could be used for quality control of the three CMs.

PMID- 17536728
TI  - High performance liquid chromatography-mass spectrometry analysis of
      protoberberine alkaloids in medicine herbs.
AB  - RP-HPLC is the main method for the analysis of alkaloids. However, peak tailing
      is a problem that commonly occurs in the separation of alkaloids. In order to
      overcome this, three kinds of RP columns were compared for the analysis of
      protoberberine alkaloids in Coptidis Rhizoma and Phellodendri Cortex in this
      work. XTerra MS C18 column was the best one which gave the best symmetry factor
      under the same conditions. With this column, a good separation of the crude
      extracts of C. Rhizoma and P. Cortex was achieved using 0.1% v/v formic acid
      buffer and methanol as mobile phase. At the same time, the crude extracts of C.
      Rhizoma and P. Cortex were analyzed by the LC-ESI-MSn and LC-atmospheric pressure
      chemical ionization (APCI)-MSn methods. In the analysis of HPLC-ESI/MSn,
      structures of five protoberberine alkaloids were elucidated, compared to
      authentic standards, and data from the literature. At the same time, the
      structure of a novel compound was elucidated. In the HPLC-APCI/ MSn analysis,
      there was an interesting phenomenon that the relative abundance of the ions M+
      and [M + 2]+ was different for different alkaloids. The possible fragmentation
      pathways of protoberberine alkaloids in APCI/MS analysis were studied for the
      first time in the present work.

PMID- 17536729
TI  - Simultaneous qualification and quantification of eight triterpenoids in radix
      achyranthis bidentatae by high-performance liquid chromatography with evaporative
      light scattering detection and mass spectrometric detection.
AB  - An HPLC with evaporative light scattering detection (ELSD) and ESI-MS was
      established for the simultaneous determination of eight triterpenoids in Radix
      Achyranthis Bidentatae. The optimal chromatographic conditions were achieved on a
      Zorbax C18 column by linear gradient elution with 0.08% v/v aqueous formic acid
      and ACN as the mobile phase at the flow rate of 0.8 mL/min. Temperature for the
      detector drift tube was set at 101 degrees C and the nitrogen flow rate was 2.8
      L/min. The identities of the analytes were accomplished by comparing retention
      times and mass data with those of reference compounds. The validation of the
      method included tests of linearity, sensitivity, repeatability, recovery, and
      stability. All the calibration curves of the eight triterpenoids showed good
      linear regression (R2 >0.997) within the test ranges. The method provides
      desirable repeatability with overall intra- and interday variations of less than
      4.9%. The obtained recoveries varied between 93.6 and 98.1% while the RSDs were
      below 3.9% (n = 3). The analysis results indicate that the content of
      investigated triterpenoids in Radix Achyranthis Bidentatae from different
      locations was greatly diverse, and the triterpenoids could be used as chemical
      markers for the discrimination of genuine and ungenuine crude drugs.

PMID- 17536730
TI  - Determination of the main bioactive metabolites of Radix salvia miltiorrhizae in
      compound Danshen dripping pills and the tissue distribution of Danshensu in
      rabbit by SPE-HPLC-MSn.
AB  - A fast solid phase extraction-high performance liquid chromatography-ion trap
      mass spectrometry (SPE-HPLC-MSn) method is presented for quantitative
      determination of 3-(3,4-dihydroxyphenyl)-2-hydroxylpropionic acid (Danshensu,
      DSS) from Compound Danshen Dripping Pills (CDDP) in rabbits' heart, liver,
      kidney, and lung and for qualitative analysis of the bioactive metabolites of
      Radix Salvia miltiorrhizae (DS) from CDDP in these tissues. The proposed method
      was validated with a detection limit of 0.06 ng/mL and a linear range of 5.0-200
      ng/mL for DSS. The main metabolites of DS were pyrocatechol, vanillic acid,
      isopropyl 3-(3,4-dihydroxyphenyl)-2-hydroxypropanoate, and 2-hydroxyl-3-(3,4
      dihydroxyphenyl)propinonic sulfuric anhydride. In vitro pharmacological
      experiments demonstrated that isopropyl 3-(3,4-dihydroxyphenyl)-2
      hydroxypropanoate had a distinct vasodilatating action.

PMID- 17536731
TI  - Rapid qualitative and quantitative analyses of flavanone aglycones in Fructus
      aurantii by HPLC ion-trap MS.
AB  - IT-MS operated in the positive mode was applied for the rapid
      characterization/quantification of the flavanones in extracts from Fructus
      aurantii. APCI-MS and CID MS/MS provide unequivocal molecular weight (MW) data of
      these compounds and useful information about their structures (diagnostic
      fragment ions). Main fragment pathways include neutral losses of H2O, C2H2O, and
      B-ring as well as a retro-Diels-Alder (RDA) fragment giving rise to [1,3A + H],
      [1,3B+H]+, and [1,4B-H2 + H]+ ions, which form the characteristic MS/MS
      "fingerprint" of flavanone aglycones. When screening extracts of F. aurantii for
      flavanone aglycones, eight target compounds were characterized using this
      fingerprint. Meanwhile, ESI-MS in full-scan mode was developed and validated for
      the quantification of the main flavanone aglycones in F. aurantii. This method is
      simple, accurate, fast and requires only 16 min per sample for direct detection
      and quantification of naringenin and hesperetin. All the results and these
      characteristic fragments showed that the IT-MS is a powerful tool for the
      structural characterization and quantitative determination offlavanone aglycones.

PMID- 17536732
TI  - Identification of unknown compounds on the basis of retention index data in
      comprehensive two-dimensional gas chromatography.
AB  - The identification of unknown compounds in complex samples is very difficult.
      Comprehensive two-dimensional gas chromatography (GC x GC) provides very good
      resolution and improved identification reliability. Mass spectrometry is a
      powerful identification tool and retention index data are another good approach
      to this end. In this study, a second-order polynomial was used to calculate
      retention index data based on n-alkanes beyond the region of the 'isovolatile'
      curve in GC x GC, and the results in the 2nd dimension were validated by using
      the same stationary phase column in one-dimensional GC. To test the usefulness of
      the method, volatile compounds in a tobacco leaf extract fraction were analyzed
      using GC x GC, and 60 compounds were identified on the basis of their retention
      indices.

PMID- 17536733
TI  - Capillary electrophoresis and microchip capillary electrophoresis with
      electrochemical and electrochemiluminescence detection.
AB  - Recent advances and key strategies in capillary electrophoresis and microchip CE
      with electrochemical detection (ECD) and electrochemiluminescence (ECL) detection
      are reviewed. This article consists of four main parts: CE-ECD; microchip CE-ECD;
      CE-ECL; and microchip CE-ECL. It is expected that ECD and ECL will become
      powerful tools for CE microchip systems and will lead to the creation of truly
      disposable devices. The focus is on papers published in the last two years (from
      2005 to 2006).

PMID- 17536734
TI  - Separation of basic and acidic compounds by capillary electrochromatography using
      monolithic silica capillary columns with zwitterionic stationary phase.
AB  - A novel monolithic silica column with zwitterionic stationary phase was prepared
      by in-situ covalent attachment of phenylalanine to a 3
      glycidoxypropyltriethoxysilane-modified silica monolith. Due to the zwitterionic
      nature of the resulting stationary phase, the density and sign of the net surface
      charge, and accordingly the direction and magnitude of electroosmotic flow in
      this column during capillary electrochromatography could be manipulated by
      adjusting the pH values of the mobile phase. CEC separations of various acidic
      and basic compounds were performed on the prepared column in anodic and weakly
      cathodic EOF modes, respectively. The peak tailing of basic compounds in CEC on a
      silica column could be alleviated at optimized buffer compositions. Besides the
      electrophoretic mechanism and weak hydrophobic interaction, weak cation- and
      anion-exchange interactions are also involved in the separations of acids and
      bases, respectively, on the zwitterionic column.

PMID- 17536735
TI  - Simultaneous determination of four tanshinones in Salvia miltiorrhiza by
      pressurized liquid extraction and capillary electrochromatography.
AB  - A pressurized liquid extraction (PLE) and CEC were developed for the simultaneous
      determination of four tanshinones (dihydrotanshinone I, cryptotanshinone,
      tanshinone I, and tanshinone IIA) in Salvia miltiorrhiza. High extraction
      efficiency (>98.5%) was achieved under the optimum PLE conditions. A good
      separation was obtained by using a Hypersil C18 capillary (3 microm, 100
      microm/25 cm) with a mixture of 30 mM Tris-HCl (pH 8.5)-ACN (1:3, v/v) as BGE
      solution running at 20 kV and 20 degrees C within 12 min. All the calibration
      curves showed good linearity (r2 >0.9958) within test ranges. The developed
      method showed good repeatability for the quantification of four investigated
      components in S. miltiorrhiza with intra- and interday variations of less than
      4.4 and 6.8%, respectively. The validated method was successfully applied to
      quantify four tanshinones in S. miltiorrhiza, which is helpful to control the
      quality of S. miltiorrhiza.

PMID- 17536736
TI  - Multiphoton excitation fluorescence: a versatile detection method for capillary
      electrophoresis.
AB  - Multiphoton excitation is a relatively old concept in quantum optics. But using
      multiphoton excitation fluorescence (MPEF) for bioanalysis is still in its
      infancy. Recently, MPEF has been introduced into the microseparation field,
      particularly CE, as a novel detection method. In this paper, MPEF detection for
      CE is reviewed, including MPEF fundamentals, approaches to achieving MPEF,
      detector configurations and applications in biological and environmental
      analyses. Emphasis will be placed on some recent advances of CE-MPEF in our
      laboratory. Challenges and future prospects are also discussed.

PMID- 17536737
TI  - Rapid speciation of iron by on-line coupling of short column capillary
      electrophoresis and inductively coupled plasma mass spectrometry with the
      collision cell technique.
AB  - A method for rapid speciation analysis of iron was developed by on-line coupling
      of short column capillary electrophoresis and inductively coupled plasma mass
      spectrometry. The collision cell technique was used to eliminate argon-based
      polyatomic interferences and a Micromist nebulizer was employed to increase the
      nebulization efficiency. Rapid speciation analysis of Fe(II) and Fe(III) was
      achieved within 1 min by short column capillary electrophoresis in a 14 cm x 50
      microm id capillary at 28 kV voltage with a mixture of 15 mmol/L
      tris(hydroxymethyl)aminomethane + 1 mmol/L 1,10-phenanthroline + 1 mmol/L EDTA
      (pH 8.6) as running electrolyte. The precisions (RSD, n = 5) of migration time
      and peak area for Fe(II) and Fe(III) were in the range of 1.0 - 2.6 and 1.9 -
      3.9%, respectively. The limits of detection (3sigma) of Fe(II) and Fe(III) were
      10.0 and 8.3 microg/L, respectively.

PMID- 17536738
TI  - Studies on degradation of imazalil enantiomers in soil using capillary
      electrophoresis.
AB  - A scheme was demonstrated to elucidate the degradation behaviors of the two
      enantiomers of the fungicide imazalil in soil using cyclodextrin-modified
      capillary zone electrophoresis. The separation buffer was 50 mmol/L NaH2PO4, 5
      mmol/L (NH4)H2PO4, and 5 mmol/L beta-cyclodextrin (pH 3.0). The limits of
      detection of this CE method were 0.24 and 0.26 microg/mL for (-)- and (+)
      imazalil, respectively. Five different soil conditions were investigated in
      laboratory microcosms: under sunlight; in darkness; under UV irradiation; in
      sterilized soil; and in soil with wheat planted in it. Radiation, microorganisms,
      and uptake by wheat benefited the degradation of imazalil in this study. The half
      lives (t1/2) of imazalil in soil under the above conditions were 20, 30.5, 11,
      27.5, and 21.5 days, respectively. The degradation rate of imazalil in soil under
      the five different sets of conditions decreased in the order: UV irradiation >
      sunlight > soil with wheat planted in it > sterilized soil > soil kept in
      darkness. Imazalil in soil (pH 8.2, slightly alkaline) collected in the suburbs
      showed non-enantioselective degradation.

PMID- 17536739
TI  - Enrichment of peptides from plasma for peptidome analysis using multiwalled
      carbon nanotubes.
AB  - Human plasma contains a complex matrix of proteolytically derived peptides
      (plasma peptidome) that may provide a correlate of biological events occurring in
      the entire organism. Analyzing these peptides from a small amount of serum/
      plasma is difficult due to the complexity of the sample and the low levels of
      these peptides. Here, we describe a novel peptidome analysis approach using
      multiwalled carbon nanotubes (MWCNTs) as an alternative adsorbent to capture
      endogenous peptides from human plasma. Harvested peptides were analyzed by using
      liquid chromatography-mass spectrometry as a means of detecting and assessing the
      adsorbed molecules. The improved sensitivity and resolution obtained by using
      liquid chromatography-mass spectrometry allowed detection of 2521 peptide
      features (m/z 300-1800 range) in about 50 microL of plasma. 374 unique peptides
      were identified with high confidence by two-dimensional liquid chromatography
      system coupled to a nano-spray ionization linear ion trap-mass spectrometer. High
      recovery of BSA digest peptides enriched with MWCNTs, in both standard buffer and
      high abundance protein solution, was observed. Comparative studies showed that
      MWCNTs were superior to C18 and C8 for the capture of the smaller peptides. This
      approach could hold promise of routine plasma peptidome analysis.

PMID- 17536740
TI  - A rapid cation-exchange HPLC method for detection and quantification of
      pyridinium oximes in plasma and tissue.
AB  - A rapid and sensitive assay for pyridinium oximes in plasma and tissue was
      developed. The method was suitable for the analysis of mono- and di-pyridinium
      oximes and utilizes ultrafiltration followed by cation-exchange high-performance
      liquid chromatography with UV detection. The assay was originally developed for
      the measurement of the oxime MMB-4 in plasma for which the lower limit of
      detection was 0.0005 pg and the limit of quantitation was 0.001 to 2.5 microg.
      The assay required as little as 50 microL of whole blood or 30 pL of tissue
      homogenate, and it was used for a pharmacokinetic study from a single
      intramuscular injection of MMB-4 (dichloride or dimethylsulfonate salt) in the
      guinea pig. Both salts were found to have similar pharmacokinetic properties in
      the plasma with a T1/2 of about 34 to 42 min and the area-under-the-curve values
      increased dose dependently. MMB-4 tissue concentrations were much lower than the
      plasma. The tissue levels peaked at 5-20 min depending on the tissue. A rank of
      concentration was diaphragm > heart > thigh muscle.

PMID- 17536741
TI  - Validation of a procedure for the gas chromatography-mass spectrometry analysis
      of cocaine and metabolites in pericardial fluid.
AB  - A method is described for the simultaneous quantification of cocaine,
      benzoylecgonine, and cocaethylene in pericardial fluid. Pericardial fluid samples
      from autopsy casework involving cocaine-related deaths and deaths unrelated to
      drug abuse were collected. The extraction of cocaine and its metabolites was
      performed using Bond-Elut Certify columns. Pericardial fluid samples were
      adjusted to pH 7 and applied to the pre-conditioned cartridges. After the washing
      steps, compounds were eluted with a mixture of chloroform/isopropanol (80:20)
      with 2% ammonium hydroxide. The dry extracts were derivatized with
      pentafluoropropionic anhydride and hexafluoroisopropanol and analyzed by gas
      chromatography-mass spectrometry using electron impact ionization and selective
      ion monitoring acquisition. Deuterated internal standards were used. The
      analytical method developed was linear, sensitive, selective, accurate, and
      sufficiently precise to be applied routinely in forensic toxicology. In this
      study, the procedure has been successfully applied to a number of forensic cases
      involving cocaine intoxication.

PMID- 17536742
TI  - Electrospray LC-MS method with solid-phase extraction for accurate determination
      of morphine-, codeine-, and ethylmorphine-glucuronides and 6-acetylmorphine in
      urine.
AB  - A method for the identification and quantification of morphine-3-glucuronide,
      codeine-6-glucuronide, ethylmorphine-6-glucuronide, and 6-acetylmorphine in human
      urine based on solid-phase extraction (SPE) and electrospray ionization liquid
      chromatography-mass spectrometry (LC-MS) was validated for use as a confirmation
      procedure in combination with immunochemical screening for opiates. Three
      deuterium-labelled analogues were used as internal standards: morphine-3
      glucuronide-d3, codeine-d3, and 6-acetylmorphine-d3. Fifty-microliter aliquots of
      urine were prepared by SPE using 30-mg Oasis HLB cartridges. The chromatographic
      system consisted of a 2.0 x 100-mm C18 column and the gradient elution buffers
      used acetonitrile and 25 mmol/L formic acid. The protonated molecular ions were
      monitored in the selected ion monitoring mode together with one qualifier ion for
      each analyte. The interassay variability was less than 10% at the reporting limit
      30 ng/mL for 6-acetylmorphine and 300 ng/mL for the other analytes. The method
      was validated by comparison with a reference gas chromatographic (GC)-MS method
      using authentic urine samples. The two methods agreed completely regarding
      identified analytes, and for the quantitative results there were slightly lower
      levels when measuring glucuronides directly as compared to total determination
      after hydrolysis by GC-MS. This result was to be expected because the free
      compounds are not measured with the LC-MS method. This study concludes that the
      presented LC-MS method is robust and reliable, and suitable for use as a
      confirmation method in clinical urine drug testing for opiates.

PMID- 17536743
TI  - The quantitation of procaine in equine plasma by liquid chromatography-linear ion
      trap mass spectrometry.
AB  - A method for the extraction and quantitation of procaine in equine plasma was
      developed for use with liquid chromatography-mass spectrometry (LC-MS). Procaine
      was isolated from equine plasma by liquid-liquid extraction at pH 11 with
      dichloromethane using procaine-d10 as an internal standard. Quantitation was
      achieved by LC-MS using a 3-microm C-18 column coupled to an electrospray
      ionization source on a linear ion-trap mass spectrometer. The limit of detection
      and limit of quantitation was determined to be 50 and 200 pg/mL, respectively.
      The lowest limit of detection determined by previous methods was 1 ng/mL.
      Administration samples were obtained as part of a larger study to determine a
      regulatory limit for procaine in racehorses and procaine concentrations were
      determined using this method.

PMID- 17536744
TI  - The reliability of fatty acid ethyl esters (FAEE) as biological markers for the
      diagnosis of alcohol abuse.
AB  - The search for biochemical markers for the objective diagnosis of alcoholism has
      been a topic of research because of the important clinical and forensic
      implications. In the last few years, two minor ethanol metabolites
      (ethylglucuronide and fatty acid ethyl esters) have been mainly investigated in
      hair samples for their ability to be incorporated into this biological matrix.
      The aim of this study was to experience the detection of fatty acid ethyl esters
      (FAEE) in the hair of alcoholics, social drinkers, and teetotallers in order to
      give a contribution to the existing literature. Hair samples from 12 alcoholics,
      10 social drinkers, and 10 teetotallers were analyzed by gas chromatography-mass
      spectrometry technique after headspace solid-phase microextraction with
      deuterated internal standards. A slight overlap in FAEE concentration between the
      three groups was found, probably because of external contamination. This
      observation suggests particular attention to the interpretation of the results.
      Nevertheless, the results obtained show the usefulness of these biochemical
      markers in the diagnosis of alcoholism.

PMID- 17536745
TI  - Evaluation of a rapid oral fluid point-of-care test for MDMA.
AB  - Cozart Bioscience Limited has developed novel lateral flow technology that allows
      the detection of drugs of abuse in biological fluids and suspect powders. This
      paper describes the application of this technology for the detection of 3,4
      methylenedioxymethamphetamine (MDMA) in oral fluid. Samples (N = 370) were
      obtained from the analytical laboratory at Cozart Bioscience Limited following
      their routine analysis for drugs of abuse. Oral fluid samples were screened for
      the presence of MDMA and methamphetamine using the Cozart RapiScan System (CRS)
      and then confirmed for the presence of amphetamines (amphetamine,
      methamphetamine, MDA, MDMA, MDEA, and MBDB) by gas chromatography-mass
      spectrometry (GC-MS). In addition to the detection of MDMA and methamphetamine,
      the CRS cross-reacts with high levels of amphetamine to give a positive result.
      One hundred and twenty-one samples screened positive using the CRS. Six of these
      samples were confirmed negative for MDMA and methamphetamine, but contained very
      high levels of amphetamine. Employing a screening cutoff of 45 ng/mL for the CRS
      and a confirmation cutoff of 30 ng/mL for GC-MS, the sensitivity, specificity,
      and accuracy were 96.6, 96.8, and 96.8%, respectively. When applying the
      Substance Abuse and Mental Health Services Administration recommended
      confirmation cutoff for amphetamines of 50 ng/mL, the sensitivity, specificity,
      and accuracy increased marginally to 98.3, 96.9, and 97.3%, respectively.

PMID- 17536746
TI  - Validation of meconin as a marker for illicit opiate use.
AB  - The detection of markers for illicit opiate misuse is important both in the
      management of substance misuse and in the postmortem identification of illicit
      opiate use. In addition to 6-monoacetylmorphine and acetyl codeine, other
      markers, such as papaverine, noscapine, and their metabolites, have been proposed
      as markers of illicit opiate use. Urine samples (362) from individuals attending
      substance misuse services and 26 postmortem cases were analyzed for meconin, a
      noscapine metabolite by gas chromatography-mass spectrometry. Three hundred of
      the substance misuse service samples and 14 of the postmortem samples had
      morphine present as the major opiate. Meconin was detected in 284 (94.7%) of
      these substance misuse samples and 11 (78%) of the postmortem samples. There was
      a specificity of 100% in both groups. In the 62 substance misuse cases where
      morphine was not the major opiate detected and four separate cases in which
      medicinal diamorphine was known to have been administered, meconin was not
      detected. The use of meconin as a useful adjunct in detecting illicit opiate use
      is recommended.

PMID- 17536747
TI  - Recent paramethoxymethamphetamine (PMMA) deaths in Taiwan.
AB  - Paramethoxyamphetamine (PMA) and paramethoxymethamphetamine (PMMA) are
      methoxylated phenylethylamine derivatives that have been banned in Taiwan since
      December 2005. The case history and pathological and toxicological findings of
      eight recent PMMA fatalities were investigated. All specimens from these cases
      were initially identified by an AxSYM fluorescence polarization immunoassay
      screening test for amphetamines with a 300 ng/mL cutoff. Specimens screened
      positive were confirmed and quantitated by gas chromatography-mass spectrometry.
      The mean age of these PMMA-related fatalities was 18.9 +/- 4.4 years in the range
      of 14-25. Seven (87.5%) of these eight cases were men. The mean, standard
      deviation, and range of PMA found in the heart blood collected from these 8 cases
      were 0.213, 0.144, and 0.079-0.489 microg/mL, respectively. The corresponding
      data for PMMA were 4.312, 4.806, and 1.208-15.824 microg/mL, respectively. Other
      drugs, such as MDA, MDMA, ketamine, norketamine, hydroxymidazolam,
      methamphetamine, and pentobarbital, were also found in these cases.

PMID- 17536748
TI  - Clenbuterol determination in calf hair by UPLC-MS-MS: case report of a fraudulent
      use for cattle growth.
AB  - A method for clenbuterol determination in hair has been developed. Hair specimens
      collected from two calves were decontaminated using hot water followed by
      methylene chloride. Hair was cut into small pieces, and 100 mg was incubated in 1
      mL 0.1M hydrochloric acid overnight at 45 degrees C in the presence of 1 ng
      acebutolol used as internal standard. After neutralization with 1 mL 0.1M NaOH, 2
      mL of bicarbonate buffer (pH 8.6) were added and the preparation was then
      purified using solid-phase extraction with an Isolute C18 column. Methanolic
      eluent was evaporated to dryness and the residue was reconstituted with 50 microL
      methanol. A 5-microL portion was injected onto an ACQUITY UPLC BEH C18 column
      (2.1 x 50 mm, 1.7 microm) and separation was achieved using a gradient of
      acetonitrile and formate buffer delivered at a flow rate of 0.6 mL/min. Detection
      was done on a Waters Micromass Quattro Micro API triple-quadrupole mass
      spectrometer. Ionization was achieved using electrospray in positive mode.
      Clenbuterol was identified by two transitions (m/z 277.1 > 203.2 and m/z 277.1 >
      132.1). Quantitation was performed with the most intensive transition (m/z 277.1
      > 203.2) versus the internal standard monitored using the transition (m/z 337.3 >
      116.1). When compared with gas chromatography methods that are generally used for
      the determination of beta-adrenergics, the major advantages of this method were
      the sensitivity, a shorter run time, and the absence of a derivatization step.
      The analysis of two hair samples from calves suspected of drug administration
      showed low clenbuterol concentrations at 3.6 and 4.8 pg/mg.

PMID- 17536749
TI  - Serum levels of olanzapine in a non-fatal overdose.
AB  - Olanzapine is a widely used second generation antipsychotic drug. Case reports of
      intoxications have been published, but reports in the literature of non-fatal
      intoxications of olanzapine containing repeated measurements of serum levels are
      scarce. Therefore, this case of non-fatal olanzapine intoxication is presented,
      in which 19 blood samples were drawn during 2 weeks. The highest (initial)
      measured value was estimated at 800 pg/L. This patient ingested 550 mg of
      olanzapine resulting in clinical signs of intoxication, including seizures.
      Because the patient was found the day after the intoxication, the initial
      concentration had probably been higher. The pharmacokinetics of olanzapine has
      been described as linear and dose-proportional throughout the therapeutic dosing
      range. Large overdoses, however, have been described to show non-linear
      pharmacokinetics. In this study's series of serum concentrations, a two-phase
      elimination was seen, with an initial elimination half-life of about 24 h during
      the first 3 days, followed by a second phase with a half-life of about 2.5 days.
      The patient in this case recovered completely. Because the elimination time after
      intoxication can be considerably longer than expected, it is recommended that the
      patient's serum concentrations after intoxication be monitored.

PMID- 17536750
TI  - Body fatness and physical activity levels of young children.
AB  - BACKGROUND: The decline in physical activity levels of young children seems to be
      combined with a high prevalence of obesity and overweight and a reduction in the
      participation in organized sport. With the ever-increasing interest in exploring
      the relationship between physical activity and obesity amongst children, it is
      important to provide a more precise estimate of both physical activity and body
      fatness. A significant proportion of previous research on this topic has relied
      on self-report methods to assess physical activity and body mass index as a proxy
      for actual body fatness. There is a need to investigate the relationships between
      physical activity and fatness in children using objective methods. AIM: This
      study was conducted in order to explore the relationship between physical
      activity patterns and percentage body fat amongst a group of primary school
      children. SUBJECTS AND METHODS: Forty-seven primary school children (boys, n =
      23; girls, n = 24) participated in this study. They were randomly selected from
      children in years 5 and 6 (9-11 year olds) of four schools drawn from the same
      catchment area in the city of Birmingham, UK. The frequency, intensity and
      duration of physical activity were determined using continuous heart rate
      monitoring from 8:30 am to 8:30pm over three separate days (two weekdays and one
      weekend day). Percentage body fat was assessed using air displacement
      plethysmography. RESULTS: Results indicated that 52% of children did not achieve
      a single 15-min bout of sustained moderate physical activity over the three days
      of monitoring. Independent t-tests revealed that girls were significantly fatter
      (t44 = -3.126, p=0.003) than boys. There was no significant difference (t45 =
      0.225, p > 0.05) between boys and girls in accumulated time spent with heart
      rates above the moderate physical activity threshold. Pearson's product moment
      correlation coefficients revealed no significant (r= -0.017, p> 0.05)
      relationship between per cent body fat and average daily time spent in moderate
      and vigorous activity. CONCLUSION: Despite the prediction to the contrary, there
      was no evidence of a significant relationship between percentage body fat of
      children and time spent in moderate and vigorous activity. Additionally, while
      there were no significant gender differences in physical activity patterns,
      children were more physically active during weekdays than weekends.

PMID- 17536751
TI  - Impact factors and research quality.

PMID- 17536752
TI  - Infant mortality and reproductive wastage associated with different genotypes of
      haemoglobinopathies in Orissa, India.
AB  - BACKGROUND: Haemoglobinopathies, including sickle-cell disease and thalassaemia
      syndrome, are a group of blood diseases mostly confined to tropical and
      subtropical regions of the world. The spectrum of haemoglobin variants is a group
      of commonly encountered genetic conditions, with an average frequency of 19.32%
      in Orissa, varying from region to region and from community to community
      depending upon the type of mating practices. AIM: For the first time, the infant
      mortality rate (IMR), i.e. the number of deaths under 1 year of age (in a given
      year) per thousand live births in a particular area, was studied to find the
      cause of the high IMR and to relate it to different genotypes of
      haemoglobinopathies. RESULTS: IMR was found to be higher in couples with sickle
      cell trait (75.9), beta-thalassaemia (184.2), and sickle cell/beta-thalassaemia
      (70.2) compared to normal couples (26.3). The reproductive wastage (abortions,
      stillbirths and neonatal deaths) and the number of deaths of offspring below 1
      year of age (infant mortality) and below 10 years of age (childhood mortality)
      among affected couples in such families were also statistically significantly
      higher compared to normal parents. CONCLUSIONS: The progeny of sickle-cell trait,
      beta-thalassaemia trait, and sickle cell/beta-thalassaemia couples contributes
      substantially to the high neonatal/IMR in the coastal state of Orissa in Central
      Eastern India. This study has revealed that in comparison to normal couples,
      couples who were carriers of haemoglobinopathies had a greater reproductive
      wastage. Screening and genetic counselling could be an important factor in
      reducing IMR in rural India. The traits/carriers of haemoglobinopathies should,
      specifically, avoid marriages and mating for the better health of subsequent
      generations.

PMID- 17536753
TI  - Cortisol and testosterone levels on a weekend and a work day in three mountain
      villages in the Selska Valley of northwest Slovenia.
AB  - BACKGROUND: In contemporary western populations, a week commonly involves 5 days
      of paid work (work days) and two non-working days (weekend). Work days are
      usually perceived as being more stressful than non-work days and this hypothesis
      has been tested in several studies, most of which selected subjects with jobs
      that are perceived to have high stress. AIM: The study measured salivary cortisol
      and testosterone on a work day and a weekend in a community-based sample of
      people going about their everyday lives and tested the hypothesis that hormone
      levels will be higher on a work day. SUBJECTS AND METHODS: Slovenian alpine
      villagers (30 females and 25 males) were sampled without reference to their
      occupation. Each individual was measured on two occasions, a day on a weekend and
      a work day as they went about their usual activities in the afternoon. RESULTS:
      Cortisol (mean = 3.32 ng ml(-1), range 0.4-27.9) and testosterone (mean = 121 pg
      ml(-1), range 17-424) values were similar to other populations. Neither the age
      of subjects nor the time in the afternoon of sample collection were associated
      with hormone concentrations. On each day of collection, cortisol and testosterone
      values were correlated for each sex, with the estimate of the correlation
      coefficient ranging from 0.57 to 0.88. For females, testosterone values were
      higher on the weekend than the work day (102 pg ml(-1) and 60 pg ml(-1),
      respectively) but not for males (mean across both days 134 pg ml(-1)).
      Independent of this effect, the presence of a spouse or other adult in the house
      was significantly associated with lower testosterone levels in both sexes.
      Husband and wife testosterone values are correlated on the weekend (r = 0.67, p =
      0.02) but not on the work day. Mean cortisol values for the weekend and work day
      were not different and there was no correlation between levels on these two days.
      CONCLUSIONS: These results, although based upon a small sample size, reveal
      potential relationships between testosterone, work-rest activities, and the
      presence-absence of a social partner that warrant further investigation.

PMID- 17536754
TI  - Mitochondrial DNA diversity of the Amerindian populations living in the Andean
      Piedmont of Bolivia: Chimane, Moseten, Aymara and Quechua.
AB  - BACKGROUND: Chimane, Moseten Aymara and Quechua are Amerindian populations living
      in the Bolivian Piedmont, a characteristic ecoregion between the eastern slope of
      the Andean mountains and the Amazonian Llanos de Moxos. In both neighbouring
      areas, dense and complex societies have developed over the centuries. The
      Piedmont area is especially interesting from a human peopling perspective since
      there is no clear evidence regarding the genetic influence and peculiarities of
      these populations. This land has been used extensively as a territory of economic
      and cultural exchange between the Andes and Amazonia, however Chimane and Moseten
      populations have been sufficiently isolated from their neighbour groups to be
      recognized as distinct populations. Genetic information suggests that
      evolutionary processes, such as genetic drift, natural selection and genetic
      admixture have formed the history of the Piedmont populations. AIM: The objective
      of this study is to characterize the genetic diversity of the Piedmont
      populations, analysing the sequence variability of the HVR-I control region in
      the mitochondrial DNA (mtDNA). Haplogroup mtDNA data available from the whole of
      Central and South America were utilized to determine the relationship of the
      Piedmont populations with other Amerindian populations. SUBJECT AND METHODS: Hair
      pulls were obtained in situ, and DNA from non-related individuals was extracted
      using a standard Chelex 100 method. A 401 bp DNA fragment of HVR-I region was
      amplified using standard procedures. Two independent 401 and 328 bp DNA fragments
      were sequenced separately for each sample. The sequence analyses included
      mismatch distribution and mean pairwise differences, median network analyses,
      AMOVA and principal component analyses. The genetic diversity of DNA sequences
      was measured and compared with other South Amerindian populations. RESULTS: The
      genetic diversity of 401 nucleotide mtDNA sequences, in the hypervariable Control
      Region, from positions 16 000-16 400, was characterized in a sample of 46
      Amerindians living in the Piedmont area in the Beni Department of Bolivia. The
      results obtained indicate that the genetic diversity in the area is higher than
      that observed in other American groups living in much larger areas and despite
      the reduced size of the studied area the human groups analysed show high levels
      of inter-group variability. In addition, results show that Amerindian populations
      living in the Piedmont are genetically more related to those in the Andean than
      in the Amazonian populations.

PMID- 17536755
TI  - Admixture estimates based on ABO, Rh and nine STRs in two Venezuelan regions.
AB  - BACKGROUND: The Venezuelan population is the product of Native American, African
      and European admixture. Few admixture studies have been made in Venezuela using
      short tandem repeats (STRs). AIM: The study estimated the contribution of each
      parental group in two Venezuelan regions: the Northern-Central and the Central
      Western Regions. SUBJECTS AND METHODS: Frequencies for ABO and Rh were estimated
      by maximum likelihood, and by direct count for nine STRs, for 211 individuals.
      Admixture was estimated using Chakraborty's gene identity method. Neighbour
      joining dendrograms were obtained with Nei's DS distance calculated between the
      two regions, the parental populations and other Venezuelan and Latin American
      populations. A principal component analysis (PCA) was also performed. RESULTS:
      For the Northern-Central Region, the estimate of admixture was 37.7% for the
      European component, 37.7% for the African and 24.6% for the Native American. For
      the Central-Western region, the estimate of admixture was 58.5% for the European,
      16.5% for the African and 25.0% for the Native American component. CONCLUSIONS:
      (i) All systems were in Hardy-Weinberg equilibrium, except the Rh blood group of
      the Central-Western Region; (ii) the European contribution is high in both
      groups; (iii) in the dendrogram and PCA, the studied populations appear close to
      other admixed populations, and their relative position with regard to the three
      parental populations coincides with the admixture analysis.

PMID- 17536756
TI  - An mtDNA perspective of French genetic variation.
AB  - BACKGROUND: The French has been insufficiently characterized so far for
      mitochondrial DNA (mtDNA) diversity. AIMS: The study aimed to enhance the
      information available for the French mtDNA pool and to explore the potential
      microgeographical differentiation of two French regions selected for their
      linguistic and historical idiosyncrasies. SUBJECTS AND METHODS: A total of 868
      samples from 12 different locations in France were collected. They were sequenced
      for the hypervariable segment I (HVS-I) and typed for haplogroup defining markers
      from the coding region either by restriction fragment length polymorphism (RFLP)
      or by a new protocol based on the 5' nuclease allelic discrimination. The mtDNA
      gene pools of French Basques and Bretons were compared in terms of frequency and
      composition with relevant neighbouring populations. RESULTS: The French Basques'
      mtDNA pool shares some common features with that of the Spanish Basques, such as
      the high frequency of haplogroup H. However, the French Basques exhibit a number
      of distinct features, most notably expressed in the prevalence of haplogroups
      linked with the Neolithic diffusion in Europe. In Brittany, Finistere shows
      closer affinities with Britain and Scandinavia than the two other departments of
      Brittany. CONCLUSION: The mtDNA haplogroup composition of the French does not
      differ significantly from the surrounding European genetic landscape. At a finer
      grain, microgeographical differentiation can be revealed, as shown for the French
      Basque country and for Brittany.

PMID- 17536757
TI  - Inheritance of six anthropometric traits in Vaidyas of West Bengal, India.
AB  - BACKGROUND: Anthropometric traits are important quantitative traits used by
      biological anthropologists. Surprisingly little is known about their pattern of
      inter-generational transmission, probably due to lack of use of developed
      statistical analysis in previous studies. AIM: The present study is an attempt to
      approach the problem of the inheritance of anthropometric traits through advanced
      statistical applications. SUBJECTS AND METHODS: Measurements of 824 individuals
      from 200 families including two generations were collected from Barasat, West
      Bengal. The study includes age correction by regression, familial correlation,
      heritability estimation and segregation analyses. RESULTS: Results showed that
      there is strong involvement of the familial component in variation of
      anthropometric traits. The magnitude of heritability (h2= 57-83%) also supports
      their strong genetic basis. The results indicated that additive genes are not the
      only contributing factor; the effect of environment is considerable and that of
      dominant genes not negligible. Due to genetic interaction with the local
      environment (specific for each trait), heritabilities vary from one trait to
      another. Length measurements have higher heritability than breadth measurements.
      Segregation analysis revealed that either the additive or dominant major gene
      (MG) is responsible for this effect, which follows simple Mendelian transmission.
      Beside this, the possibility of the existence of an additional minor gene cannot
      be discarded. CONCLUSION: Anthropometric traits have a genetic basis but their
      mode of inheritance is quite complex in nature. There is evidence of major gene
      effect (along with polygenes) with Mendelian transmission.

PMID- 17536758
TI  - Maternal early second trimester pregnancy weight in relation to birth outcome
      among Bengalee Hindus of Kolkata, India.
AB  - OBJECTIVE: The study examined to what degree maternal early second trimester
      pregnancy weight is useful and efficient in predicting birth outcome of Bengalee
      women. SUBJECTS AND METHODS: The cross-sectional retrospective study was
      conducted in a government general hospital in South Kolkata, India. This hospital
      serves the needs of people belonging to lower and lower middle class socio
      economic groups. Data were collected by one-to-one interview for confirmation of
      age, history of last menstrual period (LMP) including medical disorders. Mother's
      weight was recorded at 14-18 weeks of pregnancy from the history of LMP. Birth
      weight was measured within 24h of delivery and gestational age was assessed by
      Ballard's method using newborn physical and neurological maturity scoring. Of the
      331 Bengalees, 295 mother-baby pairs met the recruitment criteria and were
      included in this study. RESULT: Mean +/- SD maternal early second trimester
      pregnancy weight and birth weight were 45.9+/-7.0kg and 2612+/-371g,
      respectively. The difference in mean weight (3.74kg) between mothers who
      delivered low birth weight (LBW) and normal birth weight (NBW) babies was
      statistically significant (t = 4.497, p < 0.001). Overall, the prevalence of LBW
      was nearly 34%. A higher incidence of LBW and lower mean birth weight was
      observed in first quartile or low weight (< or =40 kg) mothers. The rate of LBW
      decreased (chi2 =14.47, p<0.01) and mean birth weight increased significantly
      with increasing maternal weight (F=9.218, p<0.001). Risk ratio (RR) for LBW,
      intrauterine growth retardation (IUGR) and preterm birth in low weight (first
      quartile or <40.0 kg) mothers were 2.72 (95% confidence interval (CI): 1.45
      5.10), 3.54 (95% CI: 1.17-10.74) and 1.97 (95% CI: 0.56-6.90), respectively,
      compared with heavier (>50.0kg) mothers. Finally, the present data showed that
      the maternal weight of <46.0 kg is the best cut-off for detecting LBW with 66%
      sensitivity and 75% negative predictive power. CONCLUSION: The findings suggest a
      positive association between maternal early second trimester pregnancy weight and
      birth outcome. The present study provided an efficient cut-off point for
      detecting LBW. Antenatal caregivers in health institutions and community health
      workers in the field can use this cut-off value for screening pregnant women at
      early second trimester.

PMID- 17536759
TI  - Allelic frequencies at the ACE and LRPAP1 loci suggest age-related relationships
      in a northern Italian population.
AB  - The present work attempts to determine the distribution of ACE and LRPAP1
      genotypes and allele frequencies in a sample of the population of north-western
      Italy and to examine the age-related association of these polymorphisms. ACE D
      allele frequency found in this work further confirms data obtained in previous
      studies of Northern Italian populations. Regarding the LRPAP1 gene, high
      frequencies of the deleted allele in European populations were also confirmed. In
      order to analyse the relationship between ACE and LRPAP1 gene polymorphisms and
      age, the sample was subdivided into four age groups: 1-30 (n= 99), 31-50 (n=
      165), 51-79 (n= 146) and 80-100 years old (n= 57). For the ACE gene, significant
      difference in D/D genotype frequency was found only between the younger and the
      51-79 age groups (p<0.05), the latter showing the lower frequency value.
      Significant differences were found, for both the I/D and D/D LRPAP1 genotypes,
      between the first and the second age group (p < 0.02) and between the first and
      the third age group (p < 0.01), with the 51-79 age group showing the higher D/D
      and the lower I/D genotype frequency values.

PMID- 17536760
TI  - Socio-economic status, growth, physical activity and fitness: the Madeira Growth
      Study.
AB  - BACKGROUND: Within a country social conditions change over time and these
      conditions vary from country to country. The associations between these
      conditions, somatic growth, physical activity and fitness reflect these changes.
      AIM: The study documented variation in somatic growth, physical activity and
      fitness associated with socio-economic status (SES). SUBJECTS AND METHODS: The
      study involved 507 subjects (256 boys and 251 girls) from the Madeira Growth
      Study, a mixed longitudinal study of five cohorts (8, 10, 12, 14 and 16 years of
      age) followed at yearly intervals over 3 years (1996-1998). A total of 1493
      observations were made. Anthropometric measurements included lengths, body mass,
      skeletal breadths, girths and skinfolds. Physical activity and SES were collected
      via questionnaire and interview. Physical fitness was assessed using the Eurofit
      test battery. Variation in somatic growth, physical activity and physical fitness
      by SES (high, average and low) was tested with analysis of variance. RESULTS:
      Significant differences between SES groups were observed for height, body mass
      and skinfolds. Boys and girls from high SES groups were taller, heavier and
      fatter (subscapular and triceps skinfolds) than their peers from average and low
      SES groups. At some age intervals, the high SES group had larger skeletal
      breadths (girls) and girths (boys and girls) than low SES. Small SES differences
      were observed for physical activity (sport and leisure-time indices). SES was
      significantly associated with physical fitness. At some age levels, boys from the
      low SES group performed better for muscular and aerobic endurance whereas girls
      from the high SES group performed better for power. CONCLUSION: Considerable
      variation in somatic growth and physical fitness in association with SES has been
      demonstrated, but little association was found for physical activity.

PMID- 17536761
TI  - The effects of fatness and fat distribution on respiratory functions.
AB  - BACKGROUND: Inverse relationships between respiratory function and indices of
      obesity and fat distribution have been reported, but it remains unclear which
      measure of obesity shows the strongest relationship with lung function. AIM: The
      study assessed the effect of fatness and fat distribution on respiratory
      function. SUBJECTS AND METHODS: A sample of 423 males and 509 females aged 40-50
      years were examined in the Silesian Centre for Preventive Medicine, DOLMED, in
      Wroclaw in 1995. The strength of influence of height, body mass index (BMI), wait
      to-hip ratio (WHR) and abdominal and subscapular skinfolds upon forced vital
      capacity (FVC) and forced expiratory volume in a 1-s expiration (FEV1) was
      assessed by multiple regression analysis. RESULTS: In males, FVC was strongly
      positively associated with height and BMI, but negatively associated with
      subscapular and abdominal skinfolds, WHR, and smoking. FEV1 showed a positive
      relationship with height, BMI and WHR. In females, both FVC and FEV1 showed
      significant positive associations with height, negative ones with subscapular
      skinfold, and no association with either WHR or abdominal skinfold. In males,
      respiratory function is affected to a similar extent by fat in the abdominal
      region and by fatness of the chest. In females, fatness of the thorax has the
      strongest relationship with respiratory function. CONCLUSION: Fatness tends to
      impair respiratory function in both sexes but these effects show a different
      pattern in males and females. In males, respiratory functions are significantly,
      and to a similar extant, affected by fatness in the abdominal region, both
      subcutaneous and visceral, and by fatness on the chest. In females, it is
      primarily subcutaneous fat on the upper thorax that affects respiratory
      functions, while visceral and subcutaneous abdominal fatness play little or no
      role.

PMID- 17536762
TI  - Determination of free and total S-phenylmercapturic acid by HPLC/MS/MS in the
      biological monitoring of benzene exposure.
AB  - Urinary S-phenylmercapturic acid (SPMA) is a biomarker suggested by the American
      Conference of Governmental Industrial Hygienists (ACGIH) for assessing
      occupational exposure to benzene. A possible cause of the miscorrelation between
      environmental monitoring and biological monitoring for benzene exposure, which
      many authors complain about, is the existence of a urinary metabolite that turns
      into SPMA by acid hydrolysis. Forty urine samples were tested to determine which
      concentration value would correspond to the ACGIH Biological Exposure Index (BEI)
      of 25 microg g(-1) creatinine if exposure assessment was based on the
      determination of SPMA after quantitative hydrolysis of its precursor. An aliquot
      of each sample was hydrolysed with 9 M H2SO4, a second one was brought to pH 2
      and a third one was used as it was (free SPMA). SPMA was determined by high
      performance liquid chromatography/tandem mass spectrometric technique
      (HPLC/MS/MS) using an internal standard. The analytical method was validated in
      the range 0.5-50 microg 1(-1). The average SPMA in pH 2 samples is 45-60% of the
      total, while free SPMA varies from 1% to 66%. The hydrolysis of pre-SPMA reduces
      the likelihood of variability in the results by reducing pH differences in urine
      samples and increasing the amount of measured SPMA. The BEI limit value would be
      about 50 microg g(-1) creatinine.

PMID- 17536763
TI  - The association between benzo[a]pyrene-DNA adducts and body mass index, calorie
      intake and physical activity.
AB  - Prior work suggests that body size and fat content may influence carcinogen-DNA
      adduct levels measured in white blood cells. Here we consider energy balance more
      broadly by assessing the impact of body mass index (BMI), physical activity and
      calorie intake on the presence of benzo[a]pyrene-DNA (BP-DNA) adducts in white
      blood cell DNA. Our cross-sectional study employed subjects from a separately
      conducted intervention trial. Physical activity and food intake data were
      collected at 12 and 15 months of follow-up, respectively. BP-DNA adducts were
      measured by high-performance liquid chromatography (HPLC) in white blood cell
      samples collected at 12 months of follow-up. Complete data on all variables were
      available from 143 subjects. Logistic regression showed that BMI was inversely
      associated with the presence of detectable adducts (OR = 0.90, p = 0.02), and
      that hours of moderate-intensity physical activity were positively associated
      with the presence of detectable adducts (OR = 1.04, p = 0.04). These results
      provide further evidence that body fat content influences carcinogen-DNA adduct
      levels, probably by altering the distribution of the lipophilic parent compound.

PMID- 17536764
TI  - Assessment of human exposure to di-isodecyl phthalate using oxidative metabolites
      as biomarkers.
AB  - Di-isodecyl phthalate (DiDP), primarily used as a plasticiser, is a mixture of
      isomers with predominantly ten-carbon branched side chains. Assessment of DiDP
      exposure has not been conducted before because adequate biomarkers were lacking.
      In 129 adult volunteers with no known exposure to DiDP, the urinary
      concentrations of three oxidative metabolites of DiDP: monocarboxyisononyl
      phthalate (MCiNP), monooxoisodecyl phthalate (MOiDP) and monohydroxyisodecyl
      phthalate (MHiDP), previously identified in DiDP-dosed rats, were estimated by
      solid-phase extraction coupled to high-performance liquid chromatography-tandem
      mass spectrometry (HPLC-MS/MS) using the respective oxidative metabolites of di(2
      ethylhexyl)phthalate since authentic standards of the DiDP oxidative metabolites
      were unavailable. Interestingly, the hydrolytic monoester of DiDP, monoisodecyl
      phthalate (MiDP), was not detected in any of the samples, while MCiNP, MHiDP and
      MOiDP were detected in 98%, 96% and 85%, respectively, of the samples tested.
      MCiNP was excreted predominantly in its free form, whereas MOiDP was excreted as
      its glucuronide. MCiNP, MHiDP and MOiDP eluted as clusters of multiple peaks from
      the HPLC column probably due to the presence of numerous structurally similar
      isomers present in commercial DiDP formulations. The urinary concentrations of
      these oxidative metabolites correlated significantly (p < 0.0001) with each
      other, thus confirming a common precursor. The urinary concentrations of these
      DiDP oxidative metabolites also correlated significantly (p < 0.0001) with
      oxidative metabolites of di-isononyl phthalate (DiNP) suggesting the potential
      presence of DiNP isomers in commercial DiDP or simultaneous use of DiDP and DiNP
      in consumer products. The concentrations presented are semiquantitative estimates
      and should be interpreted cautiously. Nevertheless, the higher frequency of
      detection and higher urinary concentrations of MCiNP, MHiDP and MOiDP than of
      MiDP suggest that these oxidative metabolites are better biomarkers for DiDP
      exposure assessment than MiDP. These data also suggest that unless oxidative
      metabolites are measured, the prevalence of exposure to DiDP will probably be
      underestimated.

PMID- 17536765
TI  - Using dried blood spots stored on filter paper to measure cholinesterase activity
      in wild avian species.
AB  - Birds of prey that are poisoned by cholinesterase inhibitors (e.g.
      organophosphate and carbamate insecticides) are often cared for at animal
      shelters, rehabilitation centres and wildlife diagnostic facilities. Plasma
      cholinesterase (ChE) activity is a recognized method of assessing exposure to
      these insecticides, but standard blood-handling protocols are difficult to follow
      in non-laboratory settings. The primary objective of this study was to expand
      upon a method for storing human blood on filter paper without the need for
      complicated equipment or refrigeration, and to test its utility for measurement
      of ChE activity in avian blood. ChE activity from whole blood, plasma, and dried
      blood spots was analysed from 169 wild birds and comparisons made among sample
      types. ChE activity measured in whole blood haemolysates and dried blood spots
      were significantly correlated (r = 0.74, p < 0.001), as was ChE activity measured
      in plasma and dried blood spots (r = 0.68, p < 0.001). This study demonstrated
      that monitoring pesticide exposure in birds could be conducted using elementary
      blood sampling, preserving and shipping techniques.

PMID- 17536766
TI  - Development of an expert system for the integration of biomarker responses in
      mussels into an animal health index.
AB  - Biomarkers on sentinel organisms are utilised worldwide in biomonitoring
      programs. However, the lack of effective interpretational capacity has hampered
      their uptake for use for assessment of risk in environmental management. The aim
      of the present study was to develop and test an objective decision-support or
      expert system capable of integrating biomarker results into a five-level health
      status index. The expert system is based on a set of rules derived from available
      data on responses to natural and contaminant-induced stress of marine mussels.
      Integration of parameters includes: level of biological organization; biological
      significance; mutual interrelationship; and qualitative trends in a stress
      gradient. The system was tested on a set of biomarker data obtained from the
      field and subsequently validated with data from previous studies. The results
      demonstrate that the expert system can effectively quantify the biological
      effects of different levels of pollution. The system represents a simple tool for
      risk assessment of the harmful impact of contaminants by providing a clear
      indication of the degree of stress syndrome induced by pollutants in mussels.

PMID- 17536767
TI  - Immunological and cytotoxicological responses of the Asian clam, Corbicula
      fluminea (M.), experimentally exposed to cadmium.
AB  - Bivalve molluscs, as filter-feeding organisms, are known to accumulate metals
      that can produce deleterious effects on organisms. The phagocytic activity of
      haemocytes and lysosomal alterations in the digestive gland cells were measured
      in the freshwater Asian clam exposed to cadmium, in order to assess the possible
      use of immunocompetence and lysosomal responses as biomarkers of freshwater
      quality. Clams were exposed in the laboratory to nominal concentrations of 3, 10,
      21.4, 46.5 and 100 microg 1(-1) of cadmium and sampled after 7, 15 and 30 days of
      exposure. The results show a decrease of phagocytic activity after only 7 days of
      exposure to 10 microg 1(-1) of cadmium. This response was also observed as the
      exposure time was increased. Lysosomes in the digestive cells increased in size
      and number after 7 days of exposure as cadmium concentration increased. After 30
      days of exposure, a decrease in size and number indicated a change in the
      response to the metal from concentrations of 46.5 microg 1(-1) of cadmium. A dose
      and time response both in phagocytic activity of haemocytes and lysosomal
      structure demonstrated a possible use of these biomarkers in freshwater
      biomonitoring.

PMID- 17536768
TI  - GST CYP and PON1 polymorphisms in farmers attributing ill health to
      organophosphate-containing sheep dip.
AB  - Previously we reported that in sheep dippers exposed to organophosphates the
      frequency of paraoxonase (PON1) polymorphisms differed between those with or
      without self-reported ill health. We have now examined whether polymorphisms in
      other genes involved in xenobiotic metabolism alter disease risk in this
      population. There were elevated but non-significant risks associated with the
      CYP2D6 WT genotype (odds ratio (OR) 1.47, 95% CI 0.83-2.60), or a GSTP1*B or *C
      allele (OR 1.37, 95% CI 0.88-2.01) or being GSTM1*2/GSTT1*2 homozygous (OR 1.61,
      95% CI 0.74-3.48). Similar results were generally obtained after the exclusion of
      subjects to obtain a more homogenous case-referent population: for double null
      GSTM1 and GSTT1 homozygotes the OR was 2.06 (95% CI 0.85-2.04). In those also
      likely to have been exposed to diazinon, risks associated with a GSTP1*B or *C
      allele (OR 1.82, 95% CI 0.92-3.63) or a GSTM1*2/GSTT1*2 homozygous (OR 2.60, 95%
      CI 0.72-10.42) were elevated but not to a significant extent. Risk associated
      with PON1 genotype and phenotype varied with CYP2D6 and GSTP1 genotype but not
      consistently with a priori hypotheses. Further work is necessary to delineate
      more clearly pathways of organophosphate activation and non-PON1 pathways of
      detoxification and to confirm whether CYP and GST polymorphisms alter disease
      risk in populations exposed to organophosphates.

PMID- 17536769
TI  - Serum level of soluble interleukin-2 receptor alpha correlates with the clinical
      course and activity of Wilms' tumour and soft tissue sarcomas in children.
AB  - Wilms' tumour (WT) and soft tissue sarcomas (SA) in children lack reliable
      biochemical markers. This study was carried out to determine the clinical
      significance of serum soluble interleukin-2 receptor alpha (sIL-2Ralpha) in the
      diagnostics and treatment monitoring of children with WT and SA. The study
      included 48 children: ten with WT, eight with SA and 30 healthy controls. The sIL
      2Ralpha levels (ELISA) and rates of elevated sIL-2Ralpha values were estimated
      prospectively at diagnosis and in complete remission during treatment and after
      therapy. As the dependence on age was determined, the levels of sIL-2Ralpha were
      expressed as multiplications of the upper value of the normal range for a
      particular age ( xN). Median pretreatment levels of sIL-2Ralpha in patients
      exceeded those of healthy controls (1.79 xN for WT and 1.53 for SA vs. 0.61 for
      controls; p < 0.001) as did the rates of elevated sIL-2Ralpha values (80% of
      WTand 87.5% of SA patients vs. 0% of controls). Good response to therapy was
      paralleled by a significant decline of pretreatment sIL-2Ralpha levels and its
      elevated rates. Thus, sIL-2Ralpha determination may be of some value in the
      diagnostics and treatment monitoring of childhood WT and SA.

PMID- 17536770
TI  - MN/CA9: a potential gene marker for detection of malignant cells in effusions.
AB  - Many cancers cause malignant effusions. The presence of malignant cells in
      effusions has implications in diagnosis, tumour staging and prognosis. The
      detection of malignant cells currently presents a challenge for cytopathologists.
      New adjunctive methods are needed. Although the effusions provide excellent
      materials for molecular assay, the available molecular markers are extremely
      limited, which hinders its clinical application. MN/CA9 has proved to be a
      valuable marker in many cancers such as lung, breast, colon, kidney, etc. The
      present study was to evaluate MN/CA9 as a new molecular marker for the detection
      of cancer cells in pleural effusions. Seventy-one pleural effusions including 59
      malignant effusions from patients with cancer, and 12 patients with benign
      diseases as a control, were subjected to RT-PCR for detection of MN/CA9 gene
      expression. MN/CA9 gene expression was detected in 53/59 (89.8%) pleural
      effusions from cancer patients (15/16 for breast cancers, 10/11 for lung cancers,
      4/4 for ovary cancers, 2/3 for colon-rectal cancers, 5/6 for cancers of unknown
      site, 7/8 for mesothelioma and 10/11 for other cancers). Furthermore, MN/CA9 was
      positive in 13/18 (72.2%) of cytologically negative effusions of cancer patients.
      MN/CA9 was detected in only 1/12 (8.3%) effusions from the control patients (p <
      0.01). The sensitivity and specificity of MN/CA9 gene expression were,
      respectively, 89.8% and 91.7%. Our preliminary results suggest that MN/CA9 could
      be a potential marker for the detection of malignant cells in effusions. A large
      scale study is needed to confirm these results.

PMID- 17536771
TI  - Anthropometric evaluation for primary school furniture design.
AB  - Musculoskeletal symptoms are one of the top ten health problems among
      schoolchildren in Hong Kong. Whether or not these symptoms are related to school
      furniture has yet to be determined and published data on furniture size are
      lacking. The purpose of the study was to determine whether the design of
      furniture in schools is appropriate for children's anthropometry. A total of 214
      volunteer subjects were recruited. This constituted 90% of the total number of
      primary 5 and 6 students in the studied school (i.e. those aged 10 and 13 years).
      The data collected included demographic information, data on perceived health and
      posture and body and furniture measurements. The girls' BMI was lower than that
      of the boys. The girls had longer lower limbs and wider hip breadth measurements
      in the standing position. This was similar in the sitting position. Almost none
      of the subjects had a chair with an appropriate seat height. Seat depth was found
      appropriate for large groups of students whether or not a large or small chair
      was used. Recommendations on the sizes of chairs and desks for boys and girls are
      discussed.

PMID- 17536772
TI  - Modelling diagnosis in physical therapy: a blackboard framework and models of
      experts and novices.
AB  - The primary objective of this study was to explore clinical reasoning in physical
      therapy and to highlight the similarities and differences by modelling the
      diagnostic phase of clinical reasoning. An experimental design comparing expert
      and novice physical therapists was utilized. Concurrent verbal protocols
      detailing the clinical reasoning about standardized case material were elicited.
      A framework for modelling diagnosis was specified and provided the parameters for
      analysis. The diagnostic utterances were classified as cues or hypotheses and the
      knowledge utilized was identified. The experts recruited significantly more
      knowledge than the novices (p = 0.01) and used more cues (p < 0.01). Their
      diagnoses were more accurate when compared to the original diagnosis. This
      difference between the experts and novices was reflected in the differences shown
      in the models (p < 0.01). The differences between these subjects focused upon the
      knowledge recruitment, which impacted on the accuracy of the diagnosis. The
      novices' inaccurate or non-existent diagnoses led to poor quality of treatment
      prescription. Modelling proved to be a useful way of representing these
      differences.

PMID- 17536773
TI  - Kinematics of heelstrike during walking and carrying: implications for slip
      resistance testing.
AB  - Slip resistance measurements of shoes and floors are used to evaluate the
      potential for slip and fall injuries. These measurements are believed to have
      increased validity when they more closely reflect actual heelstrike biomechanics
      during locomotion. The purpose of this study was to describe heelstrike
      kinematics during load carrying to provide data towards improved slip resistance
      testing. Foot kinematics during load carrying (unladen and carrying from 0 to
      13.5 kg) at various cadences (70, 90, 100 steps/min) was recorded. Measures
      before, during and after heelstrike were analysed. Cadence was an important
      predictor for all variables measured, associated with changes from 13% to over
      100%. The load carried was an important predictor for only the heel slip distance
      after heelstrike, but this effect needs to be investigated further. These results
      can be used to improve the fidelity of slip resistance measurements, which is
      critical to reduce slip and fall injuries in the workplace or during activities
      of daily living.

PMID- 17536774
TI  - Comparison of thermal comfort performance of two different types of road vehicle
      climate control systems.
AB  - The performance of climate control systems in vehicles becomes more and more
      important, especially against the background of the important relationship
      between compartment climate and driver mental condition and, thus, traffic
      safety. The performance of two different types of climate control systems, an un
      air-conditioned heating/cooling device (VW) and an air-conditioning climate
      control unit (BMW), is compared using modern and practical evaluation techniques
      quantifying both the dynamic 3-D temperature distribution and the local air
      refreshment rate. Both systems suffer from considerable temperature gradients:
      temperature gradients in the U-AC (VW) car up to 8-9 degrees C are encountered,
      while the AC (BMW) delivers clear improvement resulting in temperature gradients
      of 5-6 degrees C. The experiments clearly demonstrate the effect of the presence
      of even a single passenger on the thermal regime, increasing the existing thermal
      discrepancies in the compartment with 15% independent of ventilation rate.
      Furthermore, in terms of air refreshment rates in the vehicle compartment, an air
      conditioning unit halves the air refreshment time at all positions in the vehicle
      cabin, delivering a significant improvement in terms of human comfort. Similarly,
      extra air inlets in the back compartment of a car deliver progress in terms of
      cabin refreshment rate (93 s down to 50 s).

PMID- 17536775
TI  - A new framework for evaluating potential risk of back disorders due to whole body
      vibration and repeated mechanical shock.
AB  - A number of studies have examined the potential relationship between exposure to
      occupational vibration and low back pain associated with operation of vehicles.
      Only a handful of studies, however, have attempted to differentiate between the
      relative contributions of the steady state and transient mechanical shock
      components (the latter also being known as 'jarring and jolting', 'high
      acceleration event', 'multiple shocks' and 'impact') of the vibration exposure.
      The primary objective of this paper is to present a review of current studies
      that examine mechanical shock, present a case for the importance of evaluating
      both steady state and mechanical shock components and propose a new framework for
      evaluating the health effects due to occupational vibration exposure. A
      computerized bibliographical search of several databases was performed with
      special reference to the health effects of mechanical shock in relation to lower
      back disorders. Based on the analysis, eight experimental studies and nine
      epidemiological studies with relevance to exposure to 'mechanical shock' were
      identified. These studies suggested that rough vehicle rides are prevalent and
      that repeated exposure to mechanical shock may increase the risk of lower back
      pain. There is an urgent need for assessing the health effects of mechanical
      shocks in epidemiological studies. In particular, the new ISO 2631-5:
      International Organization for Standardization 2004 standard for shock exposure
      assessment should be evaluated with regard to musculoskeletal health effects.

PMID- 17536776
TI  - The influence of lift frequency, lift duration and work experience on discomfort
      reporting.
AB  - Discomfort surveys are commonly used to assess risk in the workplace and
      prioritize jobs for interventions before an injury or illness occurs. However,
      discomfort is a subjective measure and the relationship of discomfort to work
      related factors is poorly understood. The objective of this study was to
      understand how reports of discomfort relate to work-related risk factors for the
      low back. A total of 12 novice and 12 experienced manual materials handlers
      performed repetitive, asymmetric lifts at different load levels and at six
      different lift frequencies throughout an 8-h exposure period. Discomfort was
      recorded hourly throughout the day. Analyses were performed to determine which
      experimental factors influenced reporting of discomfort and if discomfort trends
      matched spine loading trends. Novice lifters reported significantly higher
      discomfort levels than experienced subjects. They also reported increases in
      discomfort as moment exposure increased and as the exposure time increased.
      Novices lifting at 8 Nm load moment level reported increased discomfort from 0.07
      to 0.63 by the end of the day, at 36 Nm they reported an increase from 0.04 to
      0.40 and at 85 Nm they reported an increase from 0.37 to 3.06. Experienced
      subjects, on the other hand, reported low levels of discomfort regardless of
      moment exposure, lift frequency or exposure duration. The reported discomforts
      were generally unrelated to the biomechanical loading on the spine. Discomfort
      reporting appears to be more a reflection of experience than of work risk factor
      exposure. Experienced subjects may have more efficient motor patterns, which
      reduce spinal load and thus discomfort. Novice subjects seemed to have a lower
      threshold of discomfort. Caution is needed when using discomfort reporting as a
      means to identify jobs in need of interventions, in that biomechanical loading
      may not be accurately represented. Discomfort should only be used as a supplement
      to objective measures, such as spinal loading, to assess the risk of low back
      disorders.

PMID- 17536777
TI  - Changes in trunk muscle activation and lumbar-pelvic position associated with
      abdominal hollowing and reach during a simulated manual material handling task.
AB  - The purpose of this study was to investigate the effect of abdominal hollowing
      (AH) on trunk muscle activation and lumbar-pelvic motion during a controlled lift
      and replace task. Surface electromyograms were recorded from five abdominal and
      two back muscle sites. Sagittal lumbar-pelvic motion was recorded by video.
      Subjects lifted a 3.8 kg load in normal, maximum and extreme reaches, first while
      performing their preferred lifting style (PLS) and then maintaining an AH
      technique. The external oblique muscle site activities were significantly higher
      (p < 0.05) for the AH technique (ranging from 7-20% of maximal voluntary
      activation (MVIC)) than at any of the abdominal sites for the PLS (ranging from 2
      10% MVIC). Differences were found among abdominal sites for the AH, but not for
      the PLS. The back muscle site activities (ranging from 9-30% MVIC) were
      significantly higher (p < 0.05) than for any of the abdominal muscles for all
      conditions, except for the anterior external oblique for AH. The pelvic and
      lumbar angles changed significantly (p < 0.05) between normal and maximal reaches
      and between techniques. The AH technique altered abdominal muscle activation
      amplitudes, with minimal differences in trunk extensors compared to the PLS. The
      AH resulted in more posterior pelvic tilt.

PMID- 17536778
TI  - Notebook input devices put to the age test: the usability of trackpoint and
      touchpad for middle-aged adults.
AB  - In two experiments, the usability of input devices integrated into computer
      notebooks was under study. The most common input devices, touchpad (experiment 1)
      and trackpoint (experiment 2) were examined. So far, the evaluation of mobile
      input devices has been restricted to younger users. However, due to ongoing
      demographic change, the main target group of mobile devices will be older users.
      Therefore, the present study focused on ageing effects. A total of 14 middle-aged
      (40-65 years) and 20 younger (20-32 years) users were compared regarding speed
      and accuracy of cursor control in a point-click and a point-drag-drop task.
      Moreover, the effects of training were addressed by examining the performance
      increase over time. In total, 640 trials per task and input device were executed.
      The results show that ageing is a central factor to be considered in input device
      design. Middle-aged users were significantly slower than younger users when
      executing the different tasks. Over time, a significant training effect was
      observed for both devices and both age groups, although the benefit of training
      was greater for the middle-aged group. Generally, the touchpad performance was
      higher than the trackpoint performance in both age groups, but the age-related
      performance decrements were less distinct when using the touchpad.

PMID- 17536779
TI  - Day of the week lost time occupational injury trends in the US by gender and
      industry and their implications for work scheduling.
AB  - While there is a growing body of research on the impact of work schedules on the
      risk of occupational injuries, there has been little investigation into the
      impact that the day of the week might have. The present research was completed to
      explore day of the week trends, reasons for such trends and the corresponding
      implications for work scheduling. Data for the number of injuries and illnesses
      involving days away from work (lost time; LT) in 2004 were provided by the US
      Bureau of Labor Statistics Office of Safety and Health Statistics. Data from the
      American Time Use Survey database were used to estimate work hours in 2004. From
      these two data sources, the rate of LT injuries and illnesses (per 200 000 work
      hours) by day of the week, industry sector and gender were estimated. The
      analysis revealed clear differences by day of the week, gender and major industry
      sector. Sundays had the highest rate overall--nearly 37% higher than the average
      of the remaining days, Monday to Saturday. Mondays had the next highest rate
      followed closely by Saturdays. This pattern was not the same for males and
      females. For males, Mondays had the highest LT rate (27% higher than the average
      of all other days) with all remaining days having essentially the same rate. For
      females, Sundays and Saturdays had much higher LT rates--122% and 60% higher,
      respectively, than the average weekday rate. There were also differences by
      industry and differences between genders by industry. The present analysis
      suggests that several factors may be contributing to the weekend and Monday
      trends observed. Lower-tenured (and younger) workers on the weekends, lower
      female management/supervision and second jobs on the weekend seem to be
      contributors to the high Saturday and Sunday LT rates. Differences in day of the
      week employment by industry did not account for the trends observed. Fraud and
      overtime also could not be confirmed as contributing to these trends. Monday
      trends were more complex to explain, with possible explanations including non
      work-related weekend injuries being reported on Mondays, soft-tissue symptoms
      becoming more noticeable on Mondays, greater Monday morning flexion risk and
      reduced supervision in the construction industry on Mondays. Interpretation of
      these trends and the implications for work scheduling are discussed.

PMID- 17536780
TI  - Understanding how the thiolate sulfur contributes to the function of the non-heme
      iron enzyme superoxide reductase.
AB  - Toxic superoxide radicals, generated via adventitious reduction of dioxygen, have
      been implicated in a number of disease states. The cysteinate-ligated non-heme
      iron enzyme superoxide reductase (SOR) degrades superoxide via reduction.
      Biomimetic analogues which provide insight into why nature utilizes a trans
      thiolate to promote SOR function are described. Spectroscopic and/or structural
      characterization of the first examples of thiolate-ligated Fe (III)-peroxo
      complexes provides important benchmark parameters for the identification of
      biological intermediates. Oxidative addition of superoxide is favored by low
      redox potentials. The trans influence of the thiolate appears to significantly
      weaken the Fe-O peroxo bond, favoring proton-induced release of H 2O 2 from a
      high-spin Fe(III)-OOH complex.

PMID- 17536781
TI  - Frontal analysis capillary electrophoresis hyphenated to electrospray ionization
      mass spectrometry for the characterization of the antithrombin/heparin
      pentasaccharide complex.
AB  - The interaction of proteins with polysaccharides represents a major and
      challenging topic in glycobiology, since such complexes mediate fundamental
      biological mechanisms. A new strategy based on the hyphenation of frontal
      analysis capillary electrophoresis (FACE) with electrospray ionization mass
      spectrometry (ESIMS) is reported for the characterization of protein/carbohydrate
      complexes. While most of the previously reported CE-MS experiments were performed
      using capillary electrophoresis in zone format, we report for the first time CE
      MS experiments in which CE was performed in frontal analysis (FACE-MS). We showed
      that the frontal mode offered a better sensitivity than zone mode and was well
      suited for the CE-MS coupling. This FACE-MS coupling was applied to the analysis
      of the complex between antithrombin and the sulfated pentasaccharide reproducing
      the antithrombin-binding sequence in heparin. The mixture of coincubated
      antithrombin and heparin pentasaccharide was continuously injected into the
      capillary, and the electrophoretic separation of the free and bound forms of the
      protein was achieved. The intact noncovalent complex antithrombin/heparin
      pentasaccharide was detected on-line by ESIMS in positive ionization mode and in
      nondenaturing sheath liquid conditions. The complex stoichiometry was determined
      from the mass measurement of the complex. In addition, the characterization of
      the sulfated pentasaccharide ligand dissociated from the complex was performed in
      negative ionization mode using a denaturing sheath liquid, allowing the
      determination of its molecular mass and sulfation features. This FACE-ESIMS
      strategy opens the way to ligand fishing experiments performed on heterogeneous
      carbohydrate mixtures and subsequent characterization of specifically bound
      carbohydrates.

PMID- 17536782
TI  - Analytical method for beta-amyloid fibrils using CE-laser induced fluorescence
      and its application to screening for inhibitors of beta-amyloid protein
      aggregation.
AB  - More than 20 million people are suffering from Alzheimer's disease, and the
      number of patients will dramatically increase with the arrival of an aging
      society unless preventive or curative medications are discovered. A fast and
      sensitive analytical method for beta-amyloid (Abeta) aggregates was developed by
      the combination of CE-laser induced fluorescence and the fluorescence reagent,
      thioflavine T. The developed method separates two different fibrils within 5 min.
      The first peak, which migrated at approximately 4 min, was supposed to be derived
      from a precursor of a fibril that migrated at approximately 3.5 min. The
      developed method was also applicable to the high-throughput screening of the
      Abeta aggregation inhibitors, which was expected to be an effective therapeutic
      agent candidate of Alzheimer's disease. Three compounds (daunomycin, 3
      indolepropionic acid (3-IPA), melatonin) were used for the assay. The order of
      the antiaggregation activity of these compounds was daunomycin > 3-IPA >
      melatonin, which was the same as that of the reported one. These results suggest
      that this analytical method may be used to analyze the Abeta fibrils and identify
      potential therapeutic agents for the treatment of Alzheimer's disease.

PMID- 17536783
TI  - Rat brain gamma-secretase activity is highly influenced by detergents.
AB  - Gamma-secretase is important for the development of Alzheimer's disease, since it
      is a crucial enzyme for the generation of the pathogenic amyloid beta-peptide
      (Abeta). Most data on gamma-secretase is derived from studies in cell lines
      overexpressing gamma-secretase components or amyloid precursor protein (APP), and
      since gamma-secretase is a transmembrane protein complex, detergents have been
      frequently used to facilitate the studies. However, no extensive comparison of
      the influence of different detergents at different concentrations on gamma
      secretase activity in preparations from brain has been made. Here, we establish
      the optimal conditions for gamma-secretase activity in rat brain, using an
      activity assay detecting endogenous production of the APP intracellular domain,
      which is generated when gamma-secretase cleaves the APP C-terminal fragments. We
      performed a subcellular fractionation and noted the highest gamma-secretase
      activity in the 100000g pellet and that the optimal pH was around 7. We found
      that gamma-secretase was active for at least 16 h at 37 degrees C and that the
      endogenous substrate levels were sufficient for activity measurements. The
      highest activity was obtained in 0.4% CHAPSO, which is slightly below the
      critical micelle concentration (0.5%) for this detergent, but the complex was not
      solubilized efficiently at this concentration. On the other hand, 1% CHAPSO
      solubilized a substantial amount of the gamma-secretase components, but the
      activity was low. The activity was fully restored by diluting the sample to 0.4%
      CHAPSO. Therefore, using 1% CHAPSO for solubilization and subsequently diluting
      the sample to 0.4% is an appropriate procedure for obtaining a soluble, highly
      active gamma-secretase from rat brain.

PMID- 17536784
TI  - Amide exchange shows calcium-induced conformational changes are transmitted to
      the dimer interface of S100B.
AB  - S100B is a 21 kDa member of the S100 calcium-binding protein family. This protein
      comprises a symmetric homodimer with each subunit having two EF-hands arranged
      from four alpha-helices (I-IV). S100B binds calcium and undergoes a conformation
      change leading to the exposure of hydrophobic surface residues that enable the
      protein to interact with biological target molecules. The most significant
      structural change that occurs during calcium binding results in a change in the
      orientation of helix III with respect to helices II and IV. In this work, the
      calcium-sensitive conformational change has been studied by utilizing fast 1H-15N
      HSQC experiments and water-transfer methods to follow the amide exchange in apo
      S100B and Ca-S100B at 35 degrees C. In apo-S100B, the protection factors are 2-3
      orders of magnitude lower for helix III than for helix I, II, or IV. In addition,
      the exchange stability measured here for the dimer interface helices (I, I', IV,
      and IV'), in the absence of calcium, is similar to the stability obtained from
      chemical denaturation experiments. When calcium binds, significant decreases in
      the protection factors for helices I and IV indicate a modification in the
      stability of the dimer interface has occurred. In contrast, helix II protection
      factors increase slightly, which is consistent with a decreased level of surface
      exposure of this helix. These data have been compared with those of the monomeric
      S100 protein, calbindin D9k, to illustrate that upon calcium binding there is a
      balance maintained between the amide exchange rates in helices II and III,
      although largely the rates are dissimilar for each of these proteins. This
      distinguishing feature may be important for the calcium-induced conformational
      change in S100B, where calcium binding is transmitted to the dimer-forming
      helices.

PMID- 17536785
TI  - Rational design, structural and thermodynamic characterization of a hyperstable
      variant of the villin headpiece helical subdomain.
AB  - A hyperstable variant of the small independently folded helical subdomain (HP36)
      derived from the F-actin binding villin headpiece was designed by targeting
      surface electrostatic interactions and helical propensity. A double mutant N68A,
      K70M was significantly more stable than wild type. The Tm of wild type in aqueous
      buffer is 73.0 degrees C, whereas the double mutant did not display a complete
      unfolding transition. The double mutant could not be completely unfolded even by
      10 M urea. In 3 M urea, the Tm of wild type is 54.8 degrees C while that of the
      N68AK70M double mutant is 73.9 degrees C. Amide H/2H exchange studies show that
      the pattern of exchange is very similar for wild type and the double mutant. The
      structures of a K70M single mutant and the double mutant were determined by X-ray
      crystallography and are identical to that of the wild type. Analytical
      ultracentrifugation demonstrates that the proteins are monomeric. The hyperstable
      mutant described here is expected to be useful for folding studies of HP36
      because studies of the wild type domain have sometimes been limited by its
      marginal stability. The results provide direct evidence that naturally occurring
      miniature protein domains have not been evolutionarily optimized for global
      stability. The stabilizing effect of this double mutant could not be predicted by
      sequence analysis because K70 is conserved in the larger intact headpiece for
      functional reasons.

PMID- 17536786
TI  - DNA-Binding ability of GAGA zinc finger depends on the nature of amino acids
      present in the beta-hairpin.
AB  - The GAGA factor of Drosophila melanogaster uses a single Cys2-His2-type zinc
      finger for specific DNA binding. Comparative sequence alignment of the GAGA zinc
      finger core with other structurally characterized zinc fingers reveals that the
      beta-hairpin of the GAGA zinc finger prefers amino acids with an aliphatic side
      chain different from those of other zinc fingers. To probe the substitution
      effect of aromatic amino acids in the beta-hairpin on the DNA binding, three
      mutant peptides were designed by substituting consensus phenylalanine, an
      aromatic amino acid, at key positions in the beta-hairpin region. The metal
      binding and the overall fold of the mutant peptides are very similar to those of
      the wild-type as shown by UV-vis absorption spectroscopy and circular dichroism
      spectroscopy. However, the gel mobility shift assay and isothermal calorimetric
      studies demonstrated that none of the mutants are able to bind the cognate DNA
      substrate, although the mutation is confined only to the beta-hairpin region. The
      present results suggest that the nature of the amino acids in the beta-hairpin
      plays an important role in the DNA-binding of the GAGA factor protein.

PMID- 17536787
TI  - Characterization of the recognition of tumor cells by the natural cytotoxicity
      receptor, NKp44.
AB  - NKp44 is a natural cytotoxicity receptor expressed by human NK cells upon
      activation. In this study, we demonstrate that cell surface heparan sulfate
      proteoglycans (HSPGs), expressed by target cells, are involved in the recognition
      of tumor cells by NKp44. NKp44 showed heparan sulfate-dependent binding to tumor
      cells; this binding was partially blocked with an antibody to heparan sulfate. In
      addition, direct binding of NKp44 to heparin was observed, and soluble
      heparin/heparan sulfate enhanced the secretion of IFNgamma by NK92 cells
      activated with anti-NKp44 monoclonal antibody. Basic amino acids, predicted to
      constitute the putative heparin/heparan sulfate binding site of NKp44, were
      mutated. Tumor cell recognition of the mutated NKp44 proteins was significantly
      reduced and correlated with their lower recognition of heparin. We previously
      reported that NKp44 recognizes the hemagglutinin of influenza virus (IV).
      Nevertheless, the ability of the mutated NKp44 proteins to bind viral
      hemagglutinin expressed by IV-infected cells was not affected. Thus, we suggest
      that heparan sulfate epitope(s) are ligands/co-ligands of NKp44 and are involved
      in its tumor recognition ability.

PMID- 17536788
TI  - H atom yields from the reactions of CN radicals with C2H2, C2H4, C3H6, trans-2
      C4H8, and iso-C4H8.
AB  - The kinetics and H atom channel yield at both 298 and 195 K have been determined
      for reactions of CN radicals with C2H2 (1.00+/-0.21, 0.97+/-0.20), C2H4 (0.96+/
      0.032, 1.04+/-0.042), C3H6 (pressure dependent), iso-C4H8 (pressure dependent),
      and trans-2-C4H8 (0.039+/-0.019, 0.029+/-0.047) where the first figure in each
      bracket is the H atom yield at 298 K and the second is that at 195 K. The
      kinetics of all reactions were studied by monitoring both CN decay and H atom
      growth by laser-induced fluorescence at 357.7 and 121.6 nm, respectively. The
      results are in good agreement with previous studies where available. The rate
      coefficients for the reaction of CN with trans-2-butene and iso-butene have been
      measured at 298 and 195 K for the first time, and the rate coefficients are as
      follows: k298K=(2.93+/-0.23)x10(-10) cm3 molecule(-1) s(-1), k195K=(3.58+/
      0.43)x10(-10) cm3 molecule(-1) s(-1) and k298K=(3.17+/-0.10)x10(-10) cm3
      molecule(-1) s(-1), k195K=(4.32+/-0.35)x10(-10) cm3 molecule(-1) s(-1),
      respectively, where the errors represent a combination of statistical uncertainty
      (2sigma) and an estimate of possible systematic errors. A potential energy
      surface for the CN+C3H6 reaction has been constructed using G3X//UB3LYP
      electronic structure calculations identifying a number of reaction channels
      leading to either H, CH3, or HCN elimination following the formation of initial
      addition complexes. Results from the potential energy surface calculations have
      been used to run master equation calculations with the ratio of primary:secondary
      addition, the average amount of downward energy transferred in a collision
      DeltaEd, and the difference in barrier heights between H atom elimination and an
      H atom 1, 2 migration as variable parameters. Excellent agreement is obtained
      with the experimental 298 K H atom yields with the following parameter values:
      secondary addition complex formation equal to 80%, DeltaEd=145 cm(-1), and the
      barrier height for H atom elimination set 5 kJ mol(-1) lower than the barrier for
      migration. Finally, very low temperature master equation simulations using the
      best fit parameters have been carried out in an increased precision environment
      utilizing quad-double and double-double arithmetic to predict H and CH3 yields
      for the CN+C3H6 reaction at temperatures and pressures relevant to Titan. The H
      and CH3 yields predicted by the master equation have been parametrized in a
      simple equation for use in modeling.

PMID- 17536789
TI  - Spin polarization, delocalization, and the effect of nonplanarity in hyperfine
      coupling constants of perfluorinated alkyl radicals.
AB  - Density functional calculations are presented on the structure and magnetic
      parameters of the perfluorinated ethyl and n-propyl radicals and compared with
      the non-fluorinated analogs. It is found that fluorine substitution leads not
      only to nonplanarity at the radical center but to delocalization of spin density
      onto the Falpha atoms and to spin polarization effects that both lead to
      pronounced anomalies in the anisotropic contribution to the hyperfine tensor. The
      nonplanar radicals do not obey the traditional McConnell relations. They serve as
      model systems for similar species that are observed in perfluorinated polymers.

PMID- 17536790
TI  - Quantum chemical evaluation of the astrochemical significance of reactions
      between S atom and acetylene or ethylene.
AB  - Addition-elimination reactions of S atom in its 3P ground state with acetylene
      (C2H2) and ethylene (C2H4) were characterized with both molecular orbital and
      density functional theory calculations employing correlation consistent basis
      sets in order to assess the likelihood that either reaction might play a general
      role in astrochemistry or a specific role in the formation of S2 (X3Sigmag-) via
      a mechanism proposed by Saxena, P. P.; Misra, A. Mon. Not. R. Astron. Soc. 1995,
      272, 89. The acetylene and ethylene reactions proceed through C2H2S (3A' ') and
      C2H4S (3A' ') intermediates, respectively, to yield HCCS (2Pi) and C2H3S (2A').
      Substantial barriers were found in the exit channels for every combination of
      method and basis set considered in this work, which effectively precludes
      hydrogen elimination pathways for both S + C2H2 and S + C2H4 in the ultracold
      interstellar medium where only very modest barriers can be surmounted and
      processes without barriers tend to predominate. However, if one or both
      intermediates are formed and stabilized efficiently under cometary or dense
      interstellar cloud conditions, they could serve as temporary reservoirs for the S
      atom and participate in reactions such as S + C2H2S --> S2 + C2H2 or S + C2H4S -
      > S2 + C2H4. For formation and stabilization to be efficient, the reaction must
      possess a barrier height small enough to be surmountable at low temperatures yet
      large enough to prevent redissociation to reactants. Barrier heights computed
      with B3LYP and large basis sets are very low, but more rigorous QCISD(T) and
      RCCSD(T) results indicate that the barrier heights are closer to 3-4 kcal/mol.
      The calculations therefore indicate that S + C2H2 or S + C2H4 could contribute to
      the formation of S2 in comets and may serve as a means to gauge coma temperature.
      The energetics of the ethylene reaction are more favorable.

PMID- 17536791
TI  - Rotational fluctuations of water confined to layered oxide materials:
      nonmonotonous temperature dependence of relaxation times.
AB  - The rotational molecular dynamics of water confined to layered oxide materials
      with brucite structure was studied by dielectric spectroscopy in the frequency
      range from 10(-2) to 10(7) Hz and in a broad temperature interval. The layered
      double hydroxide samples show one relaxation process, which was assigned to
      fluctuations of water molecules forming a layer, strongly adsorbed to the oxide
      surface. The temperature dependence of the relaxation rates has an unusual
      saddlelike shape characterized by a maximum. The model of Ryabov et al. (J. Phys.
      Chem. B 2001, 105, 1845) recently applied to describe the dynamics of water
      molecules in porous glasses is employed also for the layered materials. This
      model assumes two competing effects: rotational fluctuations of water molecules
      that take place simultaneously with defect formation, allowing the creation of
      free volume necessary for reorientation. The activation energy of rotational
      fluctuations, the energy of defect formation, a pre-exponential factor, and the
      defect concentration are obtained as main parameters from a fit of this model to
      the data. The values of these parameters were compared with those found for water
      confined to nanoporous molecular sieves, porous glasses, or bulk ice. Several
      correlations were discussed in detail, such as the lower the value of the energy
      of defect formation, the higher the number of defects. The pre-exponential factor
      increases with increasing activation energy, as an expression of the compensation
      law, and indicates the cooperative nature of the motional process. The
      involvement of the surface OH groups and of the oxygen atoms of the interlayer
      anions in the formation of hydrogen bonds was further discussed. For the
      birnessite sample, the relaxation processes are probably overlaid by a dominating
      conductivity contribution, which is analyzed in its frequency and temperature
      dependence. It is found that the conductivity of birnessite obeys the
      characteristics of semiconducting disordered materials. Especially the
      Barton/Nakajima/Namikawa relationship is fulfilled. Analyzing the temperature
      dependence of the direct current (dc) conductivity sigma0 in detail gives some
      hint that sigma0(T) has also an unusual saddlelike form.

PMID- 17536792
TI  - The solvation of Cu2+ with gas-phase clusters of water and ammonia.
AB  - A detailed study has been undertaken of the gas-phase chemistry of [Cu(H2O)N]2+
      and [Cu(NH3)N]2+ complexes. Ion intensity distributions and fragmentation
      pathways (unimolecular and collision-induced) have been recorded for both
      complexes out as far as N=20. Unimolecular fragmentation is dominated by Coulomb
      explosion (separation into two single charged units) on the part of the smaller
      ions, but switches to neutral molecule loss for N>7. In contrast, collisional
      activation promotes extensive electron capture from the collision gas, with the
      appearance of particular singly charged fragment ions being sensitive to the size
      and composition of the precursor. The results show clear evidence of the unit
      [Cu(X)8]2+ being of special significance, and it is proposed that the hydrogen
      bonded structure associated with this ion is responsible for stabilizing the
      dipositive charge on Cu2+ in aqueous solution.

PMID- 17536793
TI  - Hydration of Hg2+ in aqueous solution studied by neutron diffraction with
      isotopic substitution.
AB  - The structural parameters of Hg2+ hydration were studied in 0.225 mol/L solutions
      of Hg2+ in DNO3/D2O by means of neutron diffraction with isotopic substitution of
      199Hg for natHg. It was found that Hg2+ is hydrated by a first solvation shell of
      six water molecules. The observed Hg-O and Hg-H distances are equal to 2.48+/
      0.05 and 3.08+/-0.05 A, respectively. The angle phi between the plane of the
      water molecule and the cation-water oxygen axis is approximately 35 degrees . The
      solvation of Hg2+ therefore mimics very closely that of Ca2+ (the Ca-O and Ca-H
      distances are 2.40 and 3.03 A, respectively) and helps to account for the extreme
      toxicity of mercury(II). We note also that the Hg-O distance obtained in the
      neutron diffraction experiment is larger by approximately 0.1 A than that
      obtained by X-ray diffraction. This difference is consistent with a shift of the
      oxygen electron density toward the mercury cation due to the covalency of the Hg
      O interaction.

PMID- 17536794
TI  - Fluorescently labeled analogues of dofetilide as high-affinity fluorescence
      polarization ligands for the human ether-a-go-go-related gene (hERG) channel.
AB  - Novel fluorescent derivatives of dofetilide (1) have been synthesized. Analogues
      that feature a fluorescent probe attached through an aliphatic spacer to the
      central tertiary nitrogen of 1 have high affinity for the hERG channel, and
      affinity is dependent on both linker length and pendent dye. These variables have
      been optimized to generate Cy3B derivative 10e, which has hERG channel affinity
      equivalent to that of dofetilide. When bound to cell membranes expressing the
      hERG channel, 10e shows a robust increase in fluorescence polarization (FP)
      signal. In a FP binding assay using 10e as tracer ligand, Ki values for several
      known hERG channel blockers were measured and excellent agreement with the
      literature Ki values was observed over an affinity range of 2 nM to 3 muM. 10e
      blocks hERG channel current in electrophysiological patch clamp experiments, and
      computational docking experiments predict that the dofetilide core of 10e binds
      hERG channel in a conformation similar to that previously predicted for 1. These
      analogues enable high-throughput hERG channel binding assays that are rapid,
      economical, and predictive of test compounds' potential for prolonged QT
      liabilities.

PMID- 17536795
TI  - Thiophene-anthranilamides as highly potent and orally available factor Xa
      inhibitors.
AB  - There remains a high unmet medical need for a safe oral therapy for thrombotic
      disorders. The serine protease factor Xa (fXa), with its central role in the
      coagulation cascade, is among the more promising targets for anticoagulant
      therapy and has been the subject of intensive drug discovery efforts.
      Investigation of a hit from high-throughput screening identified a series of
      thiophene-substituted anthranilamides as potent nonamidine fXa inhibitors. Lead
      optimization by incorporation of hydrophilic groups led to the discovery of
      compounds with picomolar inhibitory potency and micromolar in vitro anticoagulant
      activity. Based on their high potency, selectivity, oral pharmacokinetics, and
      efficacy in a rat venous stasis model of thrombosis, compounds ZK 814048 (10b),
      ZK 810388 (13a), and ZK 813039 (17m) were advanced into development.

PMID- 17536796
TI  - Optimization of 1,3,4-benzotriazepine-based CCK(2) antagonists to obtain potent,
      orally active inhibitors of gastrin-mediated gastric acid secretion.
AB  - Starting from a novel, achiral 1,3,4-benzotriazepine-based CCK2 receptor
      antagonist, a process of optimization has afforded further compounds of this type
      that maintain the nanomolar affinity for recombinant, human CCK2 receptors and
      high selectivity over CCK1 receptors observed in the initial lead but display
      more potent inhibition of pentagastrin-stimulated gastric acid secretion in vivo.
      Moreover, this has largely been achieved without altering their potency at wild
      type canine and rat receptors, as judged by their displacement of [125I]-BH-CCK
      8S in a radioligand binding assay and by their activity in an isolated, perfused
      rat stomach bioassay, respectively. 2-(5-Cyclohexyl-1-(2-cyclopentyl-2-oxo-ethyl)
      2-oxo-1,2-dihydro-3H-1,3,4-benzotriazepin-3-yl)-N-(3-(5-oxo-2,5-dihydro-
      [1,2,4]oxadiazol-3-yl)-phenyl)-acetamide (47) was identified as the most
      effective compound stemming from this approach, proving to be a potent inhibitor
      of pentagastrin-stimulated gastric acid secretion in rats and dogs by intravenous
      bolus as well as by enteral administration.

PMID- 17536797
TI  - Controlled hydrothermal growth and up-conversion emission of NaLnF(4) (Ln = Y, Dy
      Yb).
AB  - The controlled hydrothermal preparation of NaYF(4) as both cubic and hexagonal
      phase types with specific associated morphologies, nanospheres and microtubes,
      respectively, has been achieved in the absence of organic solvents. The hexagonal
      NaYF(4) compound can be prepared in novel microtubular form and directly co-doped
      with Yb(3+)/Er(3+) ions. When excited by infrared light of 980 nm, these
      hexagonal NaYF(4) microtubes display strong green up-conversion emission, which
      was much more intense than that of cubic NaYF(4) or hexagonal NaYF(4)
      nanoparticles. Other related hexagonal-prismatic microtubes of NaLnF(4) (Ln = Dy
      Yb) were also synthesized. A growth mechanism for the microtubes is proposed. In
      general, the diameter of the hexagonal NaLnF(4) microtubes is strongly dependent
      on the Ln(3+) size and increases as the rare-earth ionic radius decreases.

PMID- 17536798
TI  - Nucleophilic 18F-fluorination of heteroaromatic iodonium salts with no-carrier
      added [18F]fluoride.
AB  - Diaryliodonium salts containing the 2-thienyl group as an example of an electron
      rich heteroaromatic moiety proved to be very potent precursors for the
      nucleophilic, regioselective no-carrier-added (nca) radiofluorination of various
      arenes. It even allowed the nucleophilic introduction of nca [18F]fluoride into
      electron-rich arene compounds in one step. The influences of the substitution
      pattern, of counteranions, and of different reaction conditions were studied.
      Effects of counterions could be explained by the influence of solvent on ion pair
      separation of precursor salts. Different aryl(2-thienyl)iodonium salts were used
      as precursors, where the homoaromatic group systematically varied from bearing
      electron-deficient to electron-rich substituents. Relative rates of exchange
      kinetics correlated linearly with Hammett constants of the appropriate
      substituents confirming a nucleophilic aromatic substitution reaction of high
      reactivity and low selectivity.

PMID- 17536799
TI  - Solution NMR studies of the maturation intermediates of a 13 MDa viral capsid.
AB  - Dynamic regions of proteins often play essential roles in function, assembly, or
      maturation of macromolecular complexes. When X-ray crystallography and cryo
      electron microscopy are used to investigate macromolecular structures,
      information about these dynamic regions is lost because of conformational
      disorder or flexibility. Structural studies on the precursor capsid conformations
      of the lambdoid bacteriophage HK97, a model system for macromolecular maturation,
      reveal that essential regions tend to be disordered at early maturation stages.
      In the Prohead II intermediate, the regions that have the greatest disorder are
      the N-terminal residues and the E-loop, a region involved in the formation of
      inter-subunit cross-links. The N-terminus of the subunits in the 13 MDa procapsid
      is sufficiently dynamic to be studied by solution nuclear magnetic resonance
      (NMR) spectroscopy. NMR measurements enabled the identification and assignment of
      resonances to specific residues, assessment of the region's behavior within the
      context of the capsid, and monitoring of changes in these residues during the
      maturation process. In the precursor Prohead II and immature EI-III states, the N
      termini are found to make transient interactions with the interior capsid
      surface, while at least a subset of N-termini in EI-III becomes more flexible
      with time. No resonances are observed for the fully mature Head II capsid, which
      is consistent with its completely ordered structure. NMR spectroscopy complements
      the current X-ray crystallography and cryo-electron microscopy data of HK97 by
      providing key information about the behavior of essential dynamic regions only
      inferred by other techniques.

PMID- 17536800
TI  - Rapid data collection for protein structure determination by NMR spectroscopy.

PMID- 17536801
TI  - Substrate specificity of Fpg (MutM) and hOGG1, two repair glycosylases.

PMID- 17536802
TI  - Chromophore structure of the kindling fluorescent protein asFP595 from Anemonia
      sulcata.

PMID- 17536803
TI  - Identification of a peptoid inhibitor of the proteasome 19S regulatory particle.

PMID- 17536805
TI  - Effect of acid treatment on carbon nanotube-based flexible transparent conducting
      films.

PMID- 17536804
TI  - Transition-state variation in human, bovine, and Plasmodium falciparum adenosine
      deaminases.
AB  - Adenosine deaminases (ADAs) from human, bovine, and Plasmodium falciparum sources
      were analyzed by kinetic isotope effects (KIEs) and shown to have distinct but
      related transition states. Human adenosine deaminase (HsADA) is present in most
      mammalian cells and is involved in B- and T-cell development. The ADA from
      Plasmodium falciparum (PfADA) is essential in this purine auxotroph, and its
      inhibition is expected to have therapeutic effects for malaria. Therefore, ADA is
      of continuing interest for inhibitor design. Stable structural mimics of ADA
      transition states are powerful inhibitors. Here we report the transition-state
      structures of PfADA, HsADA, and bovine ADA (BtADA) solved using competitive
      kinetic isotope effects (KIE) and density functional calculations. Adenines
      labeled at [6-13C], [6-15N], [6-13C, 6-15N], and [1-15N] were synthesized and
      enzymatically coupled with [1'-14C] ribose to give isotopically labeled
      adenosines as ADA substrates for KIE analysis. [6-13C], [6-15N], and [1
      15N]adenosines reported intrinsic KIE values of (1.010, 1.011, 1.009), (1.005,
      1.005, 1.002), and (1.004, 1.001, 0.995) for PfADA, HsADA, and BtADA,
      respectively. The differences in intrinsic KIEs reflect structural alterations in
      the transition states. The [1-15N] KIEs and computational modeling results
      indicate that PfADA, HsADA, and BtADA adopt early SNAr transition states, where
      N1 protonation is partial and the bond order to the attacking hydroxyl
      nucleophile is nearly complete. The key structural variation among PfADA, HsADA,
      and BtADA transition states lies in the degree of N1 protonation with the
      decreased bond lengths of 1.92, 1.55, and 1.28 A, respectively. Thus, PfADA has
      the earliest and BtADA has the most developed transition state. This conclusion
      is consistent with the 20-36-fold increase of kcat in comparing PfADA with HsADA
      and BtADA.

PMID- 17536806
TI  - Boronic esters as a system for crystallization-induced dynamic self-assembly
      equipped with an "on-off" switch for equilibration.

PMID- 17536807
TI  - Liquid crystalline ordering in the self-assembled monolayers of tethered rodlike
      polymers.

PMID- 17536808
TI  - The Baylis-Hillman acetates as a valuable source for one-pot multistep synthesis:
      a facile synthesis of functionalized tri-/tetracyclic frameworks containing
      azocine moiety.
AB  - The Baylis-Hillman acetates have been conveniently transformed into tri
      /tetracyclic heterocyclic frameworks containing an important azocine moiety via
      one-pot multistep protocol involving alkylation, reduction, and cyclization
      sequence.

PMID- 17536809
TI  - Formal chemoselective synthesis of leucascandrolide A.
AB  - A chemoselective synthesis of the macrocyclic core of leucascandrolide A has been
      achieved, utilizing highly enantioselective allylmetalations, an enantioselective
      Noyori reduction of a propargylic ketone and olefin metatheses as the key steps.

PMID- 17536810
TI  - A facile and modular synthesis of phosphinooxazoline ligands.
AB  - The copper(I) iodide catalyzed phosphine/aryl halide coupling procedure of
      Buchwald et al. provides modular, robust, and scaleable access to
      phosphinooxazoline (PHOX) ligands. The advantages of this method are highlighted
      by the convenient synthesis of PHOX ligands with varied steric and electronic
      properties, which would be challenging to synthesize by other protocols.

PMID- 17536811
TI  - Host-guest interactions of 4-carboxyphenoxy phthalocyanines and beta
      cyclodextrins in aqueous media.
AB  - Beta-cyclodextrin and its permethylated derivatives form 2:1 inclusion complexes
      with tetrakis- and octakis(4-carboxyphenoxy)phthalocyanines 1-4, reducing their
      aggregation tendency and promoting their sensitization of singlet oxygen
      formation in aqueous media.

PMID- 17536812
TI  - Domino metathesis involving ROM-RCM of substituted norbornenes. Rapid access to
      densely functionalized tricyclic bridged and condensed ring systems.
AB  - Domino metathesis involving ROM-RCM of appropriately constructed norbornene
      derivatives having multiple alkene chains leads to direct access of highly
      functionalized bridged tricyclic compounds while that of a compound having two
      norbornene units tethered through one carbon produces a linearly arrayed
      condensed tricyclic system.

PMID- 17536813
TI  - Stereodivergent carbometalation reactions of cyclopropenylcarbinol derivatives.
AB  - The diastereoselective formation of cyclopropylcarbinol from
      cyclopropenylcarbinol is very sensitive to the nature of the organometallic used
      for the carbometalation reaction. Both diastereoisomers can be obtained, at will,
      from the same precursor.

PMID- 17536814
TI  - Total synthesis of amphidinolide Y by formation of trisubstituted (E)-double bond
      via ring-closing metathesis of densely functionalized alkenes.
AB  - Amphidinolide Y, a 17-membered cytotoxic macrolide isolated from marine
      dinoflagellates, has been synthesized via ring-closing metathesis to assemble the
      congested trisubstituted (E)-double bond. The seco precursor was prepared from
      readily available chiral synthons with the tetrahydrofuran ring formed via 5-endo
      epoxide ring-opening cyclization. It was found that the C6-keto seco substrate
      showed higher reactivity toward Grubbs' second generation catalyst while
      Schrock's Mo catalyst was completely inactive for formation of the macrocycle.

PMID- 17536815
TI  - A mild Cu(I)-catalyzed regioselective diamination of conjugated dienes.
AB  - This paper describes a novel diamination process that uses CuCl as catalyst and
      di-tert-butyldiaziridinone as nitrogen source. A wide variety of conjugated
      dienes and a triene can be effectively diaminated in good yields with generally
      high regioselectivity under mild reaction conditions.

PMID- 17536816
TI  - Chemical characterization and anti-inflammatory effect of polysaccharides
      fractionated from submerge-cultured Antrodia camphorata mycelia.
AB  - Five polysaccharide fractions (AC-1, AC-2, AC-3, AC-4, and AC-5) were obtained
      after systemic solvent extractions and precipitations from Antrodia camphorata
      mycelia with yields of 2.92, 10.38, 1.65, 0.34, and 1.64%, respectively. Gel
      permeation chromatography (GPC) analysis showed that the distribution of mean
      molecular mass of the fractionated polysaccharides was in the range of 394-940
      kDa. The proximate compositions from each polysaccharide fraction revealed that
      all fractions belonged to the category of glycoprotein, having ratios of
      carbohydrate/protein ranging from 0.29 to 10.79 (w/w). Glucose or galactose was
      the major monosaccharide in all fractions except fraction AC-2, which has a mean
      molecular mass of 394 kDa with lyxose as the most prominent constituent. In the
      evaluation of the DPPH* radical scavenging capability, fraction AC-1 and AC-2
      polysaccharides showed the better capabilities, around 74.5 and 50.5%,
      respectively, compared to the reference control of Trolox (87.5%) at a
      concentration of 1 microM. In testing with macrophage RAW264.7 cells, fraction AC
      2 demonstrated a rather potent anti-inflammatory capability. Furthermore, the
      lipopolysaccharide-induced NO production and the protein expression by the
      inducible nitric oxide synthase (iNOS) gene were inhibited, respectively, in a
      dose-dependent (50-200 microg/mL) manner by fraction AC-2 polysaccharide.

PMID- 17536817
TI  - Cytogenetic effects of grape extracts (Vitis vinifera) and polyphenols on
      mitomycin C-induced sister chromatid exchanges (SCEs) in human blood lymphocytes.
AB  - In the present study, the effects of extracts and polyphenol-rich fractions as
      well as monomer polyphenols identified in them, from both red and white grapes,
      on mitomycin C (MMC) induced sister chromatid exchanges (SCEs) in human
      peripheral blood lymphocytes were investigated. The grape extracts and two of the
      three polyphenol-rich fractions promoted MMC-induced SCEs at concentrations from
      75 to 300 microg/mL. However, none of the extracts or fractions alone induced
      SCEs. Thus, these results suggest caution especially with regard to the use of
      grape extracts as dietary supplements. On the other hand, the fact that these
      extracts were not genotoxic alone may indicate a selective activity against
      genetically damaged cells. This is the first study regarding the clastogenic
      effects of grape extracts in human cells. Moreover, from the tested polyphenols,
      caffeic acid, gallic acid, and rutin hydrate enhanced MMC-induced clastogenicity,
      whereas ferulic acid, protocatechuic acid, (+)-catechin, (-)-epicatechin, and
      trans-resveratrol had no effect at concentrations between 5 and 100 microM. The
      differences in the chemical structures of the tested polyphenols may account for
      their differential effects on MMC clastogenicity.

PMID- 17536818
TI  - Quantitative analysis of cotton (Gossypium hirsutum) lint trash by fluorescence
      spectroscopy.
AB  - The presence of cotton plant botanical components, or trash, embedded in lint
      subsequent to harvesting and ginning is an important criterion in the
      classification of baled cotton by the U.S. Department of Agriculture Agricultural
      Marketing Service. The trash particles may be reduced in size to the point that
      specific trash types are not identifiable by image or gravimetric analysis, and
      it is desirable to quantify different trash types so that processing lines may be
      optimized for removal of the most problematic trash to enhance processing
      performance and cotton lint quality. Currently, there are no methods available to
      adequately quantify cotton lint trash based on botanical origin. The present work
      attempts to address this issue through the analysis by fluorescence spectroscopy
      of dimethyl sulfoxide extracts of mixtures of six botanical trash types. The
      fluorescence data are subsequently subjected to chemometric analysis. The
      resulting 6 partial least-squares calibration models obtained from 128 mixtures
      are demonstrated in the case of leaf and hull to be capable of predicting
      individual trash component concentrations with a high degree of confidence.

PMID- 17536819
TI  - Transepithelial transport of alpha-lipoic acid across human intestinal Caco-2
      cell monolayers.
AB  - Alpha-lipoic acid (LA) is used in dietary supplements or food with antioxidative
      functions. The mechanism for the intestinal absorption of alpha-lipoic acid was
      investigated in this study by using human intestinal Caco-2 cell monolayers. LA
      was rapidly transported across the Caco-2 cell monolayers, this transport being
      energy-dependent, suggesting transporter-mediated transport to be the mechanism
      involved. The LA transport was strongly dependent on the pH value, being
      accelerated in the acidic pH range. Furthermore, such monocarboxylic acids as
      benzoic acid and medium-chain fatty acids significantly inhibited LA transport,
      suggesting that a proton-linked monocarboxylic acid transporter (MCT) was
      involved in the intestinal transport of LA. The conversion of LA to the more
      antioxidative dihydrolipoic acid was also apparent during the transport process.

PMID- 17536820
TI  - Ethylene and alpha-farnesene metabolism in green and red skin of three apple
      cultivars in response to 1-methylcyclopropene (1-MCP) treatment.
AB  - Relationships among alpha-farnesene synthesis and oxidation, ethylene production
      and perception, antioxidative enzyme activities, and superficial scald
      development in fruit of three commercial apple cultivars were investigated at the
      biochemical and gene transcriptional levels. Scald-susceptible Cortland and Law
      Rome and scald-resistant Idared apples were untreated or treated with the
      ethylene action inhibitor 1-methylcyclopropene (1-MCP) and stored for up to 25
      weeks at 0.5 degrees C. Separate blushed (red) and unblushed (green) peel tissue
      samples were taken at harvest and after 2, 4, 6, 10, 15, 20, and 25 weeks of
      storage. Large increases in peel tissue concentrations of alpha-farnesene and its
      conjugated trienol (CTol) oxidation products occurred in untreated Cortland and
      Law Rome and were about 4-9-fold greater than those in Idared. In both Cortland
      and Law Rome, accumulation of CTols in green peel was nearly twice that in red
      peel. 1-MCP treatment delayed and attenuated alpha-farnesene and CTol
      accumulation in each cultivar. Activities of peroxidase (POX) and catalase (CAT)
      were lower in red peel than in green peel, with the exception of CAT in Law Rome,
      whereas no effects of 1-MCP on enzyme activities were detected except for
      Cortland. In control fruit, internal ethylene concentrations (IECs) increased
      during the first 4-6 weeks to reach highest levels in Cortland, intermediate
      levels in Law Rome, and low levels in Idared. In 1-MCP-treated fruit, IECs
      increased gradually to modest levels by 25 weeks in Cortland and Law Rome but
      were almost nil in Idared. Expression patterns of the alpha-farnesene synthase
      gene MdAFS1, the ethylene receptor gene MdERS1, and the ethylene biosynthetic
      genes MdACS1 and MdACO1 were generally in accord with the patterns of alpha
      farnesene and ethylene production. In particular, MdAFS1 and MdACS1 showed
      similar patterns of expression in each cultivar. Among the controls, transcript
      levels increased more rapidly in Cortland and Law Rome than in Idared during the
      first few weeks of storage. In 1-MCP-treated fruit, transcript abundance in
      Cortland and Law Rome rose to untreated control levels after 10-15 weeks but
      remained low in Idared. Scald symptoms were restricted to unblushed skin, and the
      incidence in controls after 25 weeks was nearly 100% in Cortland and Law Rome
      compared with 1% in Idared. 1-MCP treatment reduced scald incidence to 14, 3, and
      0% in Cortland, Law Rome, and Idared, respectively. Overall, the results support
      the proposed role of CTols in scald induction and indicate that alpha-farnesene
      synthesis is tightly regulated by ethylene. However, gene transcription alone
      does not account for the big differences in ethylene and alpha-farnesene
      production in Cortland, Law Rome, and Idared apples.

PMID- 17536821
TI  - Delta1-pyrroline-5-carboxylic acid formed by proline dehydrogenase from the
      Bacillus subtilis ssp. natto expressed in Escherichia coli as a precursor for 2
      acetyl-1-pyrroline.
AB  - Proline dehydrogenase (PRODH) catalyzes the biosynthesis of Delta1-pyrroline-5
      carboxylic acid (P5C). The Bacillus subtilis subsp. natto gene for the proline
      dehydrogenase (BnPRODH) was cloned and expressed in Escherichia coli. Nucleotide
      sequence analysis of the clone revealed an open-reading frame that encodes 302
      amino acid polypeptide with a calculated molecular mass of 34.5 kDa. The deduced
      amino acid sequence showed sequence similarity to bacterial PRODH and PutA of E.
      coli. The BnPRODH gene was cloned into pET21b and was expressed at a high level
      in E. coli BL21(DE3). The expressed protein was purified by using nickel ion
      affinity column chromatography to homogeneity before characterization. The
      purified recombinant BnPRODH was used to produce P5C. Model system composed of
      P5C and methylglyoxal was set up to study the formation of 2-acetyl-1-pyrroline.
      Our data showed that P5C, derived from the conversion of l-proline by the
      purified recombinant PRODH, might react directly with methylglyoxal to form 2-AP.
      P5C/methylglyoxal pathway represents the first report of a biological mechanism
      by which 2-AP may be synthesized in vitro by PRODH.

PMID- 17536822
TI  - 5-Hydroxy-3,6,7,8,3',4'-hexamethoxyflavone induces apoptosis through reactive
      oxygen species production, growth arrest and DNA damage-inducible gene 153
      expression, and caspase activation in human leukemia cells.
AB  - This study examined the growth inhibitory effects of structurally related
      polymethoxylated flavones in human cancer cells. Here, we report that 5-hydroxy
      3,6,7,8,3',4'-hexamethoxyflavone (5-OH-HxMF) induces growth inhibition of human
      cancer cells and induction of apoptosis in HL-60 cells through modulation of
      mitochondrial functions regulated by reactive oxygen species (ROS). ROS
      generation occurs in the early stages of 5-OH-HxMF-induced apoptosis, preceding
      cytochrome c release, caspase activation, and DNA fragmentation. The changes
      occurred after single breaks in DNA were detected, suggesting that 5-OH-HxMF
      induced irreparable DNA damage, which in turn triggered the process of apoptosis.
      Up-regulation of Bax was found in 5-OH-HxMF-treated HL-60 cells. In addition, a
      caspase-independent pathway indicated by endonuclease G also contributed to
      apoptosis caused by 5-OH-HxMF. Antioxidants suppress 5-OH-HxMF-induced apoptosis.
      5-OH-HxMF markedly enhanced growth arrest DNA damage-inducible gene 153 (GADD153)
      protein in a time-dependent manner. N-acetylcysteine (NAC) and catalase prevented
      up-regulation of GADD153 expression caused by 5-OH-HxMF. These findings suggest
      that 5-OH-HxMF creates an oxidative cellular environment that induces DNA damage
      and GADD153 gene activation, which in turn helps trigger apoptosis in HL-60
      cells. Meanwhile, ROS were proven an important inducer in this apoptotic process.
      The C-5 hydroxyl on the ring of 5-OH-HxMF was found to be essential for the
      antiproliferative and apoptosis-inducing activity. Our study identified the novel
      mechanisms of 5-OH-HxMF-induced apoptosis and indicated that these results have
      significant applications as potential chemopreventive and chemotherapeutic
      agents.

PMID- 17536823
TI  - Sorghum bran in the diet dose dependently increased the excretion of catechins
      and microbial-derived phenolic acids in female rats.
AB  - Sorghum bran is concentrated with procyanidins (predominately polymers), which
      may be beneficial for health in humans; however, the bioavailability of
      procyanidins is not well-understood. Female Sprague-Dawley rats were fed an
      AIN93G diet containing 0, 5, 10, 20, or 40% Hi-tannin sorghum bran (n = 5-7 for
      each group) for 50 days. Sorghum bran contained 23.3 mg/g of procyanidins. The
      urinary excretions of catechin, epicatechin, methylated catechins, and phenolic
      acids were analyzed using liquid chromatography-tandem mass spectrometry. Sorghum
      bran dose dependently increased the urinary excretion of catechin (0-2.2
      nmol/day) and 3'-O-methylcatechin (0-9.5 nmol/day). Their serum concentrations
      also increased with dose (range of 0-14 nM for 3'-O-methylcatechin). Among the 14
      phenolic acids analyzed, 3,4-dihydroxybenzoic acid, 3-methoxy-4-hydroxybenzoic
      acid, and 4-hydroxyphenylacetic acid dominated in the serum (1.8-8 micromol/L).
      In the urine, 3-methoxy-4-hydroxyphenylacetic acid, 3-hydroxyphenylacetic acid,
      and 3-hydroxyphenylpropionic acid dominated and their excretion increased
      significantly with the level of sorghum bran in the diet. The summed phenolic
      acid excretion was 0.8 micromol/day in the control group and increased to 23
      micromol/day for 40% sorghum bran group. The hippuric acid excretion ranged from
      2.2 to 16.2 micromol/day and peaked in the 10% sorghum bran group. On the basis
      of chromic oxide, a nonabsorbable marker, total procyanidins and polymers
      disappeared progressively, and significant degradation occurred in the cecum and
      colon. Catechins and procyanidins in sorghum were bioavailable; however, bacteria
      derived phenolic acids were the predominant metabolites of procyanidins.
      Procyanidins degraded in the gastrointestinal tract. Depolymerization was not
      observed.

PMID- 17536824
TI  - Fucoxanthin and fucoxanthinol enhance the amount of docosahexaenoic acid in the
      liver of KKAy obese/diabetic mice.
AB  - This study examined the effect of dietary fucoxanthin or fucoxanthinol on the
      amount of docosahexaenoic acid (DHA) in the liver of KKAy mice, a model for
      obese/type II diabetes. In the first experiment, mice were fed diets containing
      crude fucoxanthin or glyceroglycolipid for 4 weeks. Results showed a significant
      increase in the level of DHA in mice fed 0.53% crude fucoxanthin, from 2.3% in
      control mice to 5.1% of fatty acid composition of total liver lipids. On the
      other hand, in mice fed crude glyceroglycolipid, the level of DHA as a proportion
      of total liver fatty acids remained unchanged. To clarify the enhancement of
      hepatic DHA, in the second experiment, KKAy mice were fed a diet containing
      purified fucoxanthin or its deacetylated derivative, fucoxanthinol. Results from
      a quantitative analysis using an internal standard showed that in mice fed 0.2%
      fucoxanthin, the amount of hepatic DHA was 2-fold higher than in control mice,
      whereas DHA levels in the small intestine remained unchanged. Furthermore, 0.2%
      fucoxanthinol led to 1.8- and 1.2-fold increases in the amount of hepatic DHA and
      arachidonic acid compared to control mice, respectively. These results indicate
      for the first time that dietary fucoxanthin and fucoxanthinol enhance the amount
      of DHA in the liver of KKAy mice.

PMID- 17536825
TI  - Development of an analytical method for the determination of beta2-agonist
      residues in animal tissues by high-performance liquid chromatography with on-line
      electrogenerated [Cu(HIO6)2]5- -luminol chemiluminescence detection.
AB  - A novel method was developed for the simultaneous determination of beta2-agonist
      residues such as terbutaline, salbutamol, and clenbuterol by high-performance
      liquid chromatography (HPLC) coupled with chemiluminescence (CL) detection. The
      procedure was based on the enhancement effect of beta2-agonists on the CL
      reaction between luminol and the complex of trivalent copper and periodate
      ([Cu(HIO6)2]5-), which was on-line electrogenerated by constant current
      electrolysis. The HPLC separation used a Nucleosil RP-C18 column (250 mm x 4.6 mm
      i.d., 5 microm; pore size, 100 A) with a mobile phase consisting of 90%
      acetonitrile and 10% aqueous ammonium acetate (20 mmol L-1, pH 4.0) at a flow
      rate of 1.0 mL min-1. The effects of several parameters on the HPLC resolution
      and CL emission were studied systematically. Liver samples were hydrolyzed with
      beta-glucuronidase followed by a solid-phase extraction procedure using Waters
      OasisMCX cartridges. Under optimum conditions, the limits of detection at a
      signal-to-noise ratio of 3 ranged from 0.007 to 0.01 ng g-1 and the limits of
      quantification at a signal-to-noise ratio of 10 ranged from 0.023 to 0.033 ng g-1
      for three beta2-agonists. The relative standard deviations (RSDs) of intra- and
      interday precision were below 4.5%. The average recoveries for beta2-agonists
      (spiked at the levels of 0.05-5.0 ng g-1) in pig liver ranged from 84 to 110%,
      and the RSDs of the quantitative results were from 1.6 to 7.2%. The proposed
      method was successfully applied to the determination of beta2-agonist residues in
      pig liver samples.

PMID- 17536826
TI  - Altering the substrate specificity of Candida rugosa LIP4 by engineering the
      substrate-binding sites.
AB  - Candida rugosa (formerly Candida cylindracea) lipase (CRL) is an important
      industrial enzyme that is widely used in biotechnological applications such as
      the production of fatty acids and the synthesis of various esters. CRL comprises
      at least seven isozymes (LIP1-LIP7), which share a similar amino acid sequence
      but with different specificities for substrates. Previously, LIP4 was reported to
      have higher esterase activity toward long acyl-chain ester and lower lipase
      activity toward triglycerides. A296 and V344 of LIP4 were predicted to play
      decisive roles in its substrate specificity. In this study, site-specific
      saturation mutagenesis has been employed to study the substrate specificity of
      LIP4. Point mutations were separately introduced into A296 and V344 positions
      using degenerate primer sets containing 32 codons to generate two libraries of
      variants. LIP4 variants were heterologously expressed in the yeast Pichia
      pastoris. A specific plate assay was used to identify lipase-producing P.
      pastoris clones in a medium containing tributyrin. LIP4 variants with high
      activity toward short fatty acyl-chain triglyceride (tributyrin) were screened.
      Specificity analysis and biochemical characterization indicated that the
      recombinant variants A296I, V344Q, and V344H had properties remarkably different
      from those of wild-type LIP4. All three variant enzymes had significantly higher
      specific activities toward tributyrin than LIP4. In addition to short-chain
      triglyceride, A296I and V344Q also improved hydrolytic activities of
      triglycerides toward medium- and long-chain triglycerides tested. The results
      suggested that A296 played an important role in lipase activity and high
      temperature dependence of LIP4, whereas it had no effect on the chain-length
      specificity in lipolytic reaction. The V344 residue had a significant effect on
      the substrate chain-length specificity of LIP4.

PMID- 17536827
TI  - Dissipation of the herbicide benzofenap (Taipan 300) in a rice field ecosystem.
AB  - The fate of benzofenap [2-[4-(2,4-dicholoro-m-toluoyl)-1,3-dimethylpyrazol-5
      yloxy]-4'-methylacetophenone] applied to flooded rice was studied at two
      locations in New South Wales (Australia). Solid-phase extraction (SPE) was
      compared with liquid-liquid extraction (LLE) for the determination of the
      commercial chemical in water samples. SPE performed well as compared to LLE (84
      vs 80%) in irrigation waters. However, at the lower end of the concentration
      range (3 microg/L), LLE achieved higher recoveries than SPE (72 vs 59%). Rates of
      dissipation (DT50) from floodwaters and soils were measured. Dissipation of the
      herbicide from water and soil occurred fairly erratically in both mediums and can
      be best explained by a first-order decay process. The DT50 value for benzofenap
      was <1 day in irrigation water due to rapid deposition of the suspension
      concentrate formulation. The DT50 in surface soil was 44 days. The maximum
      measured concentration of benzofenap in a rice field floodwater was 39 microg/L,
      taking approximately 32 days to dissipate to <1 microg/L.

PMID- 17536828
TI  - Identification of synthetic regioisomeric lutein esters and their quantification
      in a commercial lutein supplement.
AB  - Synthetic mixtures of 24 mono- and diesters of the asymmetric hydroxylated
      carotenoid lutein with lauric, myristic, palmitic, and stearic acids were
      analyzed by liquid chromatography-ultraviolet/visible spectroscopy (LC-UV-vis)
      and characterized by LC-mass spectrometry (MS) and nuclear magnetic resonance
      spectroscopy (NMR). These compounds were then used for identifying the
      composition of a commercial lutein supplement. This is the first report of
      chromatographic separation of mixed fatty acid lutein diesters. Preferential MS
      loss of fatty acids or water occurred initially at the 3'-hydroxy position in the
      epsilon-ionone ring and subsequently at the 3-hydroxy position in the beta-ionone
      ring. This selective fragmentation leads to facile assignment of the specific
      fatty acids to the appropriate regioisomeric ionone ring. A commercial lutein
      supplement contained low levels of two pairs of regioisomeric monoesters and
      nearly equal levels of three homogeneous diesters and five pairs of mixed
      diesters. Palmitic acid was the predominant fatty acid, with lower amounts of
      myristic, stearic, and lauric acids.

PMID- 17536829
TI  - Gluten-free sorghum bread improved by sourdough fermentation: biochemical,
      rheological, and microstructural background.
AB  - This study was conducted to improve the quality and theoretical understanding of
      gluten-free sorghum bread. The addition of 2% hydroxypropyl methylcellulose
      improved bread based on 105% water, 70% sorghum flour, and 30% potato starch.
      Nevertheless, a flat top and tendency toward a hole in the crumb remained.
      Sourdough fermentation of the total sorghum flour eliminated these problems. Size
      exclusion high-performance liquid chromatography demonstrated that during
      sourdough fermentation, proteins from the dough liquid were degraded to peptides
      smaller than kafirin monomers (<19 kDa). Laser scanning confocal microscopy
      showed aggregated protein in bread crumb without sourdough fermentation, whereas
      with sourdough fermentation, only small isolated patches of protein bodies
      embedded in matrix protein remained. In oscillatory temperature sweeps, sourdough
      fermentation caused a significantly higher resistance to deformation (|G*|) after
      gelatinization of the above batter relative to batters without sourdough. Results
      suggest that a strong starch gel, without interference of aggregated protein, is
      desirable for this type of bread.

PMID- 17536830
TI  - Analysis of alternariol and alternariol monomethyl ether on flavedo and albedo
      tissues of tangerines (Citrus reticulata) with symptoms of alternaria brown spot.
AB  - A method was developed for the quantification of alternariol and alternariol
      monomethyl ether on tangerines with and without symptoms of Alternaria brown spot
      disease. The method employs solid-phase extraction for cleanup, followed by high
      performance liquid chromatography coupled with tandem mass spectrometry (HPLC
      MS/MS) for detection. This method was validated on flavedo (exocarp or epicarp,
      exterior yellow peel) and on albedo tissue (mesocarp, interior white peel). An
      excellent linearity over a range of 0.50-20.0 mg/kg was achieved, with r2 >or=
      0.997. The limits of detection (LOD) and quantification (LOQ) were fewer than
      0.13 and 0.50 microg/kg, respectively. The relative standard deviations (RSDs)
      were <or=14.4% during the validation. The levels of these mycotoxins on flavedo
      of fruits with symptoms vary from 2.54 +/- 0.24 to 17.40 +/- 1.05 mug/kg.
      Surprisingly, neither alternariol nor altenariol monomethyl ether was detected on
      albedo tissues, suggesting that flavedo works as a barrier for such substances.

PMID- 17536831
TI  - Solid foodstuff supplemented with phenolics from grape: antioxidant properties
      and correlation with phenolic profiles.
AB  - Osmotic dehydration was assessed as an operation for supplementing a solid
      foodstuff (a gel was used as the model food) with grape phenolics from a
      concentrated red grape must to increase its antioxidant properties. The model
      food was processed for up to 24 h, and the osmotic pressure was adjusted by
      diluting the concentrated red grape must. In all conditions tested, low molecular
      weight phenolics (<or=610 g/mol) and, in particular, trans-caftaric acid, trans
      coutaric acid, ferulic acid, coumaric acid, caffeic acid (hydroxycinnamic acids),
      gallic acid (hydroxybenzoic acids), quercetin, and rutin (flavonols), were
      quantified in the red grape must and also in the osmo-dehydrated food. Other
      flavonoids such as (+)-catechin and (-)epicatechin (flavan-3-ols) were detected
      only in the red grape must. Trolox equivalent antioxidant activity (TEAC) and
      ferric reducing antioxidant power (FRAP) were determined in the osmo-dehydrated
      food. Under the conditions that maximized phenolic infusion, the total phenolic
      content of the gel was close to the values reported in some rich-in-phenolic
      fruits and vegetables, whereas TEAC was 3 times that of fresh fruit with the
      highest antioxidant capacity. Regression analysis showed that the individual
      phenolics analyzed significantly explain the antioxidant capacity of the osmo
      dehydrated food.

PMID- 17536832
TI  - Purification and characterization of alginate lyase from streptomyces species
      strain A5 isolated from banana rhizosphere.
AB  - To characterize the alginate lyase produced by rhizosphere Streptomyces,
      Streptomyces sp. A5 was isolated from banana rhizosphere, and its extracellular
      lyase was purified to an electrophoretically homogeneous state. The lyase has a
      molecular mass of 32 kDa by sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis (SDS-PAGE). The optimum temperature and pH were 37 degrees C and
      pH 7.5, respectively. Ninety-two percent of the activity was lost after
      incubation at 70 degrees C and pH 7.5 for 20 min. The enzyme was inhibited by
      0.05 M SDS and 2 mM Hg2+, Cu2+, and Fe3+, but EDTA enhanced the enzyme activity.
      The Km value of the lyase was 0.13 mg mL-1 with the substrate sodium alginate.
      The lyase had substrate specificity for polyguluronate units in the alginate
      molecules. The alginate oligomers prepared by the lyase show growth-promoting
      activity on the roots of banana plantlets. These results indicated that the
      encapsulation method using alginate microbeads to inoculate beneficial
      streptomycete strains might be beneficial to the root growth of banana plantlets.

PMID- 17536833
TI  - Investigation of adsorption behavior of (-)-epigallocatechin gallate on bovine
      serum albumin surface using quartz crystal microbalance with dissipation
      monitoring.
AB  - Quartz crystal microbalance with dissipation monitoring (QCM-D) has been employed
      to study the interactions between (-)-epigallocatechin gallate (EGCG) and bovine
      serum albumin (BSA) surface. The adsorbed mass, thickness, and viscoelastic
      properties of EGCG adlayer on BSA surface at various EGCG concentrations,
      temperatures, sodium chloride concentrations, and pH values have been determined
      by QCM-D in combination with the Voigt model. The adsorption isotherm of EGCG on
      BSA surfaces can be better described by the Freundlich model than the Langmuir
      model, indicating that EGCG adsorption on BSA surfaces is dominated by
      nonspecific hydrophobic interactions, as supported by stronger EGCG adsorption at
      higher temperature. Shifts in the Fourier transform infrared spectra of the BSA
      surface with and without EGCG adsorption disclose that hydrogen bonding might
      also be involved in EGCG adsorption on BSA surfaces. The addition of salt and
      change of pH can also influence the EGCG adsorption on BSA surfaces. Usually,
      higher EGCG adsorption leads to higher values of viscosity and shear elastic
      modulus of EGCG adlayer, which can be explained by the aggregation of BSA through
      EGCG bridges. Compared with EGCG, nongalloylated (+)-catechin shows much lower
      adsorption capacity on BSA surfaces, suggesting the importance of the galloyl
      group in polyphenol/protein interactions.

PMID- 17536834
TI  - Impact of redox agents on the extractability of gluten proteins during bread
      making.
AB  - The gluten proteins gliadin and glutenin are important for dough and bread
      characteristics. In the present work, redox agents were used to impact gluten
      properties and to study gliadin-glutenin interactions in bread making. In control
      bread making, mixing increased the extractability of glutenin. The level of SDS
      extractable glutenin decreased during fermentation and then further in the oven.
      The levels of extractable alpha- and gamma-gliadin also decreased during bread
      baking due to gliadin-glutenin polymerization. Neither oxidizing nor reducing
      agents had an impact on glutenin extractabilities after mixing. The redox
      additives did not affect omega-gliadin extractabilities during bread making due
      to their lack of cysteine residues. Potassium iodate (0.82-2.47 micromol/g of
      protein) and potassium bromate (1.07-3.17 micromol/g of protein) increased both
      alpha- and gamma-gliadin extractabilities during baking. Increasing
      concentrations of glutathione (1.15-3.45 micromol/g of protein) decreased levels
      of extractable alpha- and gamma-gliadins during baking. The work not only
      demonstrated that, during baking, glutenin and gliadin polymerize through heat
      induced sulfhydryl-disulfide exchange reactions, but also demonstrated for the
      first time that oxidizing agents, besides their effect on dough rheology and
      hence bread volume, hinder gliadin-glutenin linking during baking, while
      glutathione increases the degree of covalent gliadin to glutenin linking.

PMID- 17536835
TI  - Formation of amyloid fibrils via longitudinal growth of oligomers.
AB  - Mature amyloid fibrils are believed to be formed by the lateral association of
      discrete structural units designated as protofibrils, but this lateral
      association of protofibrils has never been directly observed. We have recently
      characterized a thioesterase from Alcaligenes faecalis, which was shown to exist
      as homomeric oligomers with an average diameter of 21.6 nm consisting of 22 kDa
      subunits in predominantly beta-sheet structure. In this study, we have shown that
      upon incubation in a 75% ethanol solution, the oligomeric particles of protein
      were transformed into amyloid-like fibrils. TEM pictures obtained at various
      stages during fibril growth helped us to understand to a certain extent the early
      events in the fibrillization process. When incubated in 75% ethanol, oligomeric
      particles of protein grew to approximately 35-40 nm in diameter before fusion.
      Fusion of two oligomers of 35-40 nm resulted in the formation of a fibril. Fibril
      formation was accompanied by a reduction in the diameter of the particle to
      approximately 20-25 nm along with concomitant elongation to approximately 110 nm,
      indicating reorganization and strengthening of the structure. The elongation
      process continued by sequential addition of oligomeric units to give fibers 500
      1000 nm in length with a further reduction in diameter to 17-20 nm. Further
      elongation resulted in the formation of fibers that were more than 4000 nm in
      length; the diameter, however, remained constant at 17-20 nm. These data clearly
      show that the mature fibrils have assembled via longitudinal growth of oligomers
      and not via lateral association of protofibrils.

PMID- 17536836
TI  - Structural, thermodynamic, and mutational analyses of a psychrotrophic RNase HI.
AB  - Ribonuclease (RNase) HI from the psychrotrophic bacterium Shewanella oneidensis
      MR-1 was overproduced in Escherichia coli, purified, and structurally and
      biochemically characterized. The amino acid sequence of MR-1 RNase HI is 67%
      identical to that of E. coli RNase HI. The crystal structure of MR-1 RNase HI
      determined at 2.0 A resolution was highly similar to that of E. coli RNase HI,
      except that the number of intramolecular ion pairs and the fraction of polar
      surface area of MR-1 RNase HI were reduced compared to those of E. coli RNase HI.
      The enzymatic properties of MR-1 RNase HI were similar to those of E. coli RNase
      HI. However, MR-1 RNase HI was much less stable than E. coli RNase HI. The
      stability of MR-1 RNase HI against heat inactivation was lower than that of E.
      coli RNase HI by 19 degrees C. The conformational stability of MR-1 RNase HI was
      thermodynamically analyzed by monitoring the CD values at 220 nm. MR-1 RNase HI
      was less stable than E. coli RNase HI by 22.4 degrees C in Tm and 12.5 kJ/mol in
      DeltaG(H2O). The thermodynamic stability curve of MR-1 RNase HI was characterized
      by a downward shift and increased curvature, which results in an increased
      DeltaCp value, compared to that of E. coli RNase HI. Site-directed mutagenesis
      studies suggest that the difference in the number of intramolecular ion pairs
      partly accounts for the difference in stability between MR-1 and E. coli RNases
      HI.

PMID- 17536837
TI  - Calcicludine binding to the outer pore of L-type calcium channels is
      allosterically coupled to dihydropyridine binding.
AB  - How dihydropyridines modulate L-type voltage-gated Ca2+ channels is not known.
      Dihydropyridines bind cooperatively with Ca2+ binding to the selectivity filter,
      suggesting that they alter channel activity by promoting structural
      rearrangements in the pore. We used radioligand binding and patch-clamp
      electrophysiology to demonstrate that calcicludine, a toxin from the venom of the
      green mamba snake, binds in the outer vestibule of the pore and, like Ca2+, is a
      positive modulator of dihydropyridine binding. Data were fit using an allosteric
      scheme where dissociation constants for dihydropyridine and calcicludine binding,
      KDHP and KCaC, are linked via the coupling factor, alpha. Nine acidic amino acids
      located within the S5-Pore-helix segment of repeat III were sequentially changed
      to alanine in groups of three, resulting in the mutant channels, Mut-A, Mut-B,
      and Mut-C. Mut-A, whose substitutions are proximal to IIIS5, exhibits a 4.5-fold
      reduction in dihydropyridine binding and is insensitive to calcicludine binding.
      Block of Mut-A currents by calcicludine is indistinguishable from wild-type,
      indicating that KCaC is unchanged and that the coupling between dihydropyridine
      and calcicludine binding (i.e., alpha) is disrupted. Mut-B and Mut-C possess KDHP
      values that resemble that of the wild type. Mut-C, the most C-terminal of the
      mutant channels, is insensitive to calcicludine binding and block. KCaC values
      for the Mut-C single mutants, E1122A, D1127A, and D1129A, increase from 0.3 (wild
      type) to 1.14, 2.00, and 20.5 microM, respectively. Together, these findings
      suggest that dihydropyridine antagonist and calcicludine binding to L-type Ca2+
      channels promote similar structural changes in the pore that stabilize the
      channel in a nonconducting, blocked state.

PMID- 17536838
TI  - The two-component system Bacillus respiratory response A and B (BrrA-BrrB) is a
      virulence factor regulator in Bacillus anthracis.
AB  - Bacillus anthracis, a bioterrorism threat as well as an agricultural concern, has
      complex mechanisms for regulation of its major virulence factors. Genome searches
      identified the putative two-component system that we designated Bacillus
      anthracis respiratory response (Brr)A-BrrB. A brrA deletion strain was
      constructed, and real-time reverse transcriptase polymerase chain reaction and
      Western blot analysis were used to assess the effect of BrrA-BrrB on levels of
      virulence factors, the regulator atxA, and growth characteristics. When brrA was
      deleted, the genes for anthrax toxins (lethal factor, protective antigen, and
      edema factor) where expressed 4-6-log10-fold less than in the parent Sterne
      strain. The global regulator atxA was downregulated when compared to atxA in the
      Sterne strain. Thus, the BrrA-BrrB two-component system positively regulates B.
      anthracis toxin genes as well as the atxA regulator. Aerobic growth was not
      affected by the DeltabrrA mutation, but colonies showed differences in
      morphology, the mutant did not sporulate, and the strain lost the ability to
      synthesize cytochrome aa3. Gel-shift mobility assays demonstrated that BrrA bound
      to the promoters of genes for both protective antigen and cytochrome aa3,
      demonstrating that BrrA is a transcription factor. BrrA-BrrB has sequence
      similarity with the virulence regulator SrrA-SrrB in Staphylococcus aureus and
      the aerobic/anaerobic regulator, ResD-ResE, in B. subtilis, and appears to share
      regulatory mechanisms with ResD-ResE.

PMID- 17536839
TI  - Inhibiting gene expression with locked nucleic acids (LNAs) that target
      chromosomal DNA.
AB  - Oligonucleotides containing locked nucleic acid bases (LNAs) have increased
      affinity for complementary DNA sequences. We hypothesized that enhanced affinity
      might allow LNAs to recognize chromosomal DNA inside human cells and inhibit gene
      expression. To test this hypothesis, we synthesized antigene LNAs (agLNAs)
      complementary to sequences within the promoters of progesterone receptor (PR) and
      androgen receptor (AR). We observed inhibition of AR and PR expression by agLNAs
      but not by analogous oligomers containing 2'-methoxyethyl bases or
      noncomplementary LNAs. Inhibition was dose dependent and exhibited IC50 values of
      <10 nM. Efficient inhibition depended on the length of the agLNA, the location of
      LNA bases, the number of LNA substitutions, and the location of the target
      sequence within the targeted promoter. LNAs targeting sequences at or near
      transcription start sites yielded better inhibition than LNAs targeting
      transcription factor binding sites or an inverted repeat. These results
      demonstrate that agLNAs can recognize chromosomal target sequences and
      efficiently block gene expression. agLNAs could be used for gene silencing, as
      cellular probes for chromosome structure, and therapeutic applications.

PMID- 17536840
TI  - Inhibiting gene expression with peptide nucleic acid (PNA)--peptide conjugates
      that target chromosomal DNA.
AB  - Peptide nucleic acids (PNAs) are nonionic DNA/RNA mimics that can recognize
      complementary sequences by Watson-Crick base pairing. The neutral PNA backbone
      facilitates the recognition of duplex DNA by strand invasion, suggesting that
      antigene PNAs (agPNAs) can be important tools for exploring the structure and
      function of chromosomal DNA inside cells. However, before agPNAs can enter wide
      use, it will be necessary to develop straightforward strategies for introducing
      them into cells. Here, we demonstrate that agPNA-peptide conjugates can target
      promoter DNA and block progesterone receptor (PR) gene expression inside cells.
      Thirty-six agPNA-peptide conjugates were synthesized and tested. We observed
      inhibition of gene expression using cationic peptides containing either arginine
      or lysine residues, with eight or more cationic amino acids being preferred. Both
      13 and 19 base agPNA-peptide conjugates were inhibitory. Inhibition was observed
      in human cancer cell lines expressing either high or low levels of progesterone
      receptor. Modification of agPNA-peptide conjugates with hydrophobic amino acids
      or small molecule hydrophobic moieties yielded improved potency. Inhibition by
      agPNAs did not require cationic lipid or any other additive, but adding agents to
      cell growth media that promote endosomal release caused modest increases in agPNA
      potency. These data demonstrate that chromosomal DNA is accessible to agPNA
      peptide conjugates and that chemical modifications can improve potency.

PMID- 17536841
TI  - Dual-specificity tyrosine phosphorylation-regulated kinase 1A does not require
      tyrosine phosphorylation for activity in vitro.
AB  - The dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A) gene
      is localized in human chromosome 21, and its overexpression has been associated
      with the learning and memory deficits of Down syndrome. DYRK1A contains a
      Y319XY321 motif shared by all members of the DYRK protein kinase family. Residue
      Y321 in the motif is phosphorylated in DYRK1A prepared from Escherichia coli and
      from eukaryotic cells. It has been proposed that the YXY motif is an equivalent
      of the TXY motif, the activation loop, of mitogen-activated protein kinase and
      that phosphorylation at the motif is required for DYRK activity. In this study,
      the role of tyrosine phosphorylation in the activity of DYRK1A was investigated
      in detail. Wild-type DYRK1A with a reduced level of phosphotyrosine (pY) was
      prepared by treating E. coli-produced DYRK1A with two different protein tyrosine
      phosphatases. The resulting pY-depleted DYRK1A could not regain pY during
      autophosphorylation but was as active as the untreated control. These findings
      were further supported by the observation that DYRK1A retained significant
      enzymatic activity when both tyrosine residues in the YXY motif were replaced
      with either histidine or glutamine. Together, we conclude that tyrosine
      phosphorylation and tyrosine residues in the YXY motif are not directly involved
      in DYRK1A enzymatic activity in vitro.

PMID- 17536842
TI  - The TatA subunit of Escherichia coli twin-arginine translocase has an N-in
      topology.
AB  - The twin-arginine translocase (Tat) system is used by many bacteria to
      translocate folded proteins across the cytoplasmic membrane. The TatA subunit is
      the predicted pore-forming subunit and has been shown to form a homo-oligomeric
      complex. Through accessibility experiments using the thiol-reactive reagents 4
      acetamido-4'-maleimidylstilbene-2,2'-disulfonic acid and Nalpha-(3
      maleimidylproprionyl)biocytin toward site-specific cysteine mutants in TatA, we
      show that the N-terminus of TatA is located in the cytoplasm rather than the
      previously assumed periplasm. We also confirm previous observations that the C
      terminus has a dual topology. By treatment with the membrane uncoupler carbonyl
      cyanide-m-chlorophenyl hydrazone, we show that the topological state of the C
      terminus is dependent on the membrane potential. These results suggest two
      architectures of TatA in the membrane: one with a single transmembrane helix and
      the other with two transmembrane helices. Molecular models of both topologies
      were used to develop and cartoon a homo-oligomeric complex as a channel with a
      diameter of approximately 50 A and suggest that the double transmembrane helix
      topology might be the building block for the translocation channel. Additionally,
      in vivo cross-linking experiments of Gly2Cys and Thr22Cys mutants showed that
      Gly2, at the beginning of transmembrane helix-1, is in close proximity with Gly2
      of a neighboring TatA, as Cys2 cross-linked immediately upon the addition of
      copper phenanthroline. On the other hand, Cys22, at the other end of the
      transmembrane helix, took at least 10 min to cross-link, suggesting that a
      possible movement or reorientation is required to bring this residue into
      proximity with a neighboring TatA subunit.

PMID- 17536843
TI  - Determination of degradation pathways and kinetics of acyl glucuronides by NMR
      spectroscopy.
AB  - Acyl glucuronides have been implicated in the toxicity of many xenobiotics and
      marketed drugs. These toxicities are hypothesized to be a consequence of covalent
      binding of the reactive forms of the acyl glucuronide to proteins. Reactive
      intermediates of the acyl glucuronide arise from the migration of the aglycone
      leading to other positional and stereoisomers under physiological conditions. In
      order to screen for the potential liabilities of these metabolites during the
      early phase of pharmaceutical development, an NMR method based on the
      disappearance of the anomeric resonance of the O-1-acyl glucuronide was used to
      monitor the degradation kinetics of 11 structurally diverse acyl glucuronides,
      including those produced from the known nonsteroidal anti-inflammatory drugs
      (NSAIDs). The acyl glucuronides were either chemically synthesized or were
      isolated from biological matrices (bile, urine, and liver microsomal extracts).
      The half-lives attained utilizing this method were found to be comparable to
      those reported in the literature. NMR analysis also enabled the delineation of
      the two possible pathways of degradation: acyl migration and hydrolytic cleavage.
      The previously characterized 1H resonances of acyl migrated products are quite
      distinguishable from those that arise from hydrolysis. The NMR method described
      here could be used to rank order acyl glucuronide forming discovery compounds
      based on the potential reactivity of the conjugates and their routes of
      decomposition under physiological conditions. Furthermore, we have shown that in
      vitro systems such as liver microsomal preparations can be used to generate
      sufficient quantities of acyl glucuronides from early discovery compounds for NMR
      characterization. This is particularly important, as we often have limited supply
      of early discovery compounds to conduct in vivo studies to generate sufficient
      quantities of acyl glucuronides for further characterization.

PMID- 17536844
TI  - Directed electroless growth of metal nanostructures on patterned self-assembled
      monolayers.
AB  - The directed placement of Cu nanostructures on surfaces has been studied using a
      combination of scanning probe lithography and electroless metal deposition onto
      nanopatterned SAMs of 16-mercaptohexadecanoic acid (16-MHA) on Au. In situ
      studies using nanoscale molecular gradients reveal how controlling the areal
      density of the 16-MHA molecules dictates the nucleation and growth of the metal
      nanostructures. The influence of controlling pattern line spacing and tip path on
      pattern feature fidelity is also discussed.

PMID- 17536845
TI  - Layer-by-layer nanoassembly of polyelectrolytes using formamide as the working
      medium.
AB  - Formamide, in its pure state, has been used as a working solvent for layer-by
      layer (LbL) polyelectrolyte self-assembly. Polystyrene sulfonate (PSS) and
      polyallylamine hydrochloride (PAH) polyelectrolyte films were deposited onto
      planar substrates and colloidal particles. Film deposition was confirmed using
      quartz crystal microbalance and zeta potential measurements. Formamide was used
      as an alternative to the water-based working solvents commonly used for LbL self
      assembly. Few LbL self-assembly studies using nonaqueous solvents have been
      reported. Most studies performed with nonaqueous solvents have required the
      addition of small volumes of water to dissolve the polyelectrolytes. Conversely,
      the high dielectric constant of pure formamide led to the dissolution and
      transport of PSS and PAH. Using formamide, it is possible to deposit nanometer
      thick polyelectrolyte films onto water-sensitive surfaces. Formamide can be thus
      be used for encapsulating water sensitive hydrogen storage materials within
      polyelectrolyte films.

PMID- 17536846
TI  - Enhanced stabilization of emulsions due to surfactant-induced nanoparticle
      flocculation.
AB  - We have shown recently (Binks, B. P.; Rodrigues, J. A.; Frith, W. J. Langmuir
      2007, 23, 3626) that, for mixtures of negatively charged silica nanoparticles and
      cationic surfactant, oil-in-water emulsions are most stable to creaming and
      coalescence at conditions of maximum flocculation of particles by surfactant in
      aqueous dispersions alone. Here, we extend the idea using positively charged
      silica particles in mixtures with anionic surfactant.

PMID- 17536847
TI  - Ion-specific forces between a colloidal nanoprobe and a charged surface.
AB  - We investigate the effect of ion-specific potentials on the force between a
      nanoprobe attached to a cantilever tip, and a charged surface. The probe is
      treated as a spherical nanoparticle with constant charge. A modified Poisson
      Boltzmann equation in bispherical coordinates is used to address this problem in
      a more quantitative way. We predict that the ion-specific series of measured
      forces depend on the sign and magnitude of surface charge densities.

PMID- 17536848
TI  - Protein synthesis patterns reveal a complex regulatory response to singlet oxygen
      in Rhodobacter.
AB  - Singlet oxygen (1O2) is a stress factor and signal in the facultative
      phototrophic bacterium Rhodobacter sphaeroides. In vivo protein labeling with L
      [35S]-methionine and analysis by two-dimensional gel electrophoresis revealed
      that the synthesis of 61 proteins was changed in response to 1O2. After 1O2
      treatment, protein synthesis patterns were distinct from those after H2O2
      treatment but similar to those after high light exposure. This indicates
      regulatory mechanisms selective for different reactive oxygen species (ROS) and a
      response to light partly mediated by 1O2. Analysis of mutant strains support that
      the response to 1O2 is regulated mainly by rpoE (sigma E), but also a modulation
      of the sigma E dependent response by other factors and the existence of sigma E
      independent responses. The involvement of the RNA chaperon Hfq in the 1O2
      response implies a role of small regulatory RNAs.

PMID- 17536849
TI  - Hypothermia affects translocation of numerous cytoplasmic proteins following
      global cerebral ischemia.
AB  - Using a decapitation ischemia model, we studied translocation of proteins to and
      from the cytosol in normothermic (NT) and hypothermic (HT) rat brains. 2D gel
      analysis identified 74 proteins whose cytosolic level changed significantly after
      15 min of ischemia. HT preserved the cytosolic levels of several glycolytic
      enzymes, as well as many plasticity related proteins, otherwise decreased
      following NT ischemia. The levels of redox-related proteins was lower in HT than
      in NT. Our results indicate that translocation of proteins to and from the
      cytosol is an important issue during ischemia.

PMID- 17536850
TI  - Dynamic light scattering study of salt effect on phase behavior of pig vitreous
      body and its microscopic implication.
AB  - The salt effects on phase equilibrium and dynamical properties of pig vitreous
      body was studied by the macroscopic observation of the swelling behavior and
      dynamic light scattering under various conditions. It was found that the vitreous
      body collapses with maintaining the shape when the concentrations of salts (NaCl,
      CaCl2, and MgCl2) were changed. From the observations of the dynamics of light
      scattered by the pig vitreous body, intensity autocorrelation functions that
      revealed two diffusion coefficients, Dfast and Dslow were obtained. We developed
      the theory for describing the density fluctuation of the entities in the vitreous
      gel system with sodium hyaluronate filled in the meshes of the collagen fiber
      network. The dynamics of collagen and sodium hyaluronate explains two relaxation
      modes of the fluctuation. The diffusion coefficient of collagen obtained from
      Dfast and Dslow is very close to that in aqueous solution, which suggests the
      vitreous body is in the swollen state. Divergent behavior in the measured total
      scattered light intensities and diffusion coefficients upon varying the
      concentration of salt was observed. Namely, a slowing down of the dynamic modes
      accompanied by increased "static" scattered intensities was observed. This is
      indicative of the occurrence of a phase transition upon salt concentration.

PMID- 17536851
TI  - Theoretical determination of the standard reduction potentials of pheophytin-a in
      N,N-dimethyl formamide and membrane.
AB  - Quantum mechanical/molecular mechanics (QM/MM) calculations were performed on the
      neutral, anionic, and dianionic forms of Pheophytin-a (Pheo-a) in N,N-dimethyl
      formamide (DMF) in order to calculate the absolute free energy of reduction of
      Pheo-a in solution. The geometry of the solvated species was optimized by
      restricted open-shell density functional treatment (ROB3LYP) using the 6-31G(d)
      basis set for the molecular species while the primary solvent shell consisting of
      45 DMF molecules was treated by the MM method using the universal force field
      (UFF). Electronic energies of the neutral, anionic, and dianionic species were
      obtained by carrying out single point density functional theory (DFT)
      calculations using the 6-311+G(2d,2p) basis set on the respective ONIOM optimized
      geometries. The CHARMM27 force field was used to account for the dynamical nature
      of the primary solvation shell of 45 DMF molecules. In the calculations using
      solvent shells, the required atomic charges for each solvent molecule were
      obtained from ROB3LYP/6-31G(d) calculation on a single isolated DMF molecule.
      Randomly sampled configurations generated by the Monte Carlo (MC) technique were
      used to determine the contribution of the primary shell to the free energy of
      solvation of the three species. The dynamical nature of the primary shell
      significantly corrects the free energy of solvation. Frequency calculations at
      the ROB3LYP/6-31G(d) level were carried out on the optimized geometries of
      truncated 47-atom models of the neutral and ionic species in vacuum so as to
      determine the differences in thermal energy and molecular entropy. The Born
      energy of ion-dielectric interaction, the Onsager energy of dipole-dielectric
      interaction, and the Debye-Huckel energy of ion-ionic cloud interaction for the
      pheophytin-solvent aggregate were added as perturbative corrections. The Born
      interaction also makes a large contribution to the absolute free energy of
      reduction. An implicit solvation model (DPCM) was also employed for the
      calculation of standard reduction potentials in DMF. Both the models were
      successful in reproducing the standard reduction potentials. An explicit solvent
      treatment(QM/MM/MC + Born + Onsager + Debye corrections) yielded the one electron
      reduction potential of Pheo-a as -0.92 +/- 0.27 V and the two electron reduction
      potential as -1.34 +/- 0.25 V at 298.15 K, while the implicit solvent treatment
      yielded the corresponding values as -1.03 +/- 0.17 and -1.30 +/- 0.17 V,
      respectively. The calculated values more or less agree with the experimental
      midpoint potentials of -0.90 and -1.25 V, respectively. Moreover, a numerical
      finite difference Poisson-Boltzmann solver (FDPB) along with the DPCM methodology
      was employed to obtain the reduction potential of pheophytin in the thylakoid
      membrane. The calculated reduction potential value of -0.58 V is in excellent
      agreement with the reported value -0.61 V.

PMID- 17536852
TI  - Nonergodic arrested state in diluted clay suspensions monitored by triple-quantum
      23Na nuclear magnetic resonance.
AB  - The aging of water suspension of the synthetic clay Laponite has been studied by
      liquid-state triple-quantum filter nuclear magnetic resonance techniques, in a
      range of clay weight concentration (Cw = 0.012-0.028) known as the isotropic
      phase. Counterions dynamic parameters (rotational correlation time tauc and
      quadrupolar coupling constant e2qQ/h) have been extracted from sodium triple
      quantum filtered experimental data within the multi-exponential quadrupolar
      relaxation theory in the fast exchange approximation. By monitoring quadrupolar
      sodium ions dynamical (tauc and e2qQ/h) and static (counterion concentration pb)
      properties during the aging, we find two different mechanisms of transition
      toward an arrested state. Our experimental findings match with the description
      which states, at low concentration, the formation of clusters of Laponite disks
      trigger the reaching of the arrested state, while at high concentration, single
      disks are the basic units of the arrested phase. The procedure proposed in this
      paper, based on multiple quantum filtered NMR data analysis, results to be a
      useful means to study the routes to arrested states in aqueous colloidal
      dispersions.

PMID- 17536853
TI  - Salting out near the critical point.
AB  - The salting out of solid solutes near the critical point of the solvent is
      investigated using the results of a previous paper (J. Phys. Chem. B 2006, 110,
      24077) on the fluctuation theory of salting out. It is found that the salting out
      coefficient at infinite dilution of cosolvent is approximately proportional to
      the compressibility of the solvent and is consequently quite large near the
      critical point. No estimate is given for the range of cosolvent concentrations
      over which the infinite dilution slope might be a good approximation. Far from
      the critical point, it is known to be a good approximation over a considerable
      cosolvent concentration range.

PMID- 17536854
TI  - Probing heme coordination states of inducible nitric oxide synthase with a
      ReI(imidazole-alkyl-nitroarginine) sensitizer-wire.
AB  - Mammalian inducible nitric oxide synthase (iNOS) catalyzes the production of l
      citrulline and nitric oxide (NO) from L-arginine and O2. The Soret peak in the
      spectrum of the iNOS heme domain (iNOSoxy) shifts from 423 to 390 nm upon
      addition of a sensitizer-wire, [ReI-imidazole-(CH2)8-nitroarginine]+, or
      [ReC8argNO2]+, owing to partial displacement of the water ligand in the active
      site. From analysis of competitive binding experiments with imidazole, the
      dissociation constant (Kd) for [ReC8argNO2]+-iNOSoxy was determined to be 3.0+/
      0.1 microM, confirming that the sensitizer-wire binds with higher affinity than
      both L-arginine (Kd=22+/-5 microM) and imidazole (Kd=14+/-3 microM). Laser
      excitation (355 nm) of [ReC8argNO2]+-iNOSoxy triggers electron transfer to the
      active site of the enzyme, producing a ferroheme in less than approximately 1
      micros.

PMID- 17536855
TI  - Crystallization behavior of soft, attractive microgels.
AB  - The equilibrium phase behavior and the dynamics of colloidal assemblies composed
      of soft, spherical, colloidal particles with attractive pair potentials have been
      studied by digital video microscopy. The particles were synthesized by
      precipitation copolymerization of N-isopropylacrylamide (NIPAm), acrylic acid
      (AAc), and N,N'-methylene bis(acrylamide) (BIS), yielding highly water swollen
      hydrogel microparticles (microgels) with temperature- and pH-tunable swelling
      properties. It is observed that in a pH = 3.0 buffer with an ionic strength of 10
      mM, assemblies of pNIPAm-AAc microgels crystallize due to a delicate balance
      between weak attractive and soft repulsive forces. The attractive interactions
      are further confirmed by measurements of the crystal melting temperatures. As the
      temperature of colloidal crystals is increased, the crystalline phase does not
      melt until the temperature is far above the lower critical solution temperature
      (LCST) of the microgels, in stark contrast to what is typically observed for
      phases formed due to purely repulsive interactions. The unusual thermal stability
      of pNIPAm-AAc colloidal crystals demonstrates an enthalpic origin of
      crystallization for these microgels.

PMID- 17536856
TI  - Nocardichelins A and B, siderophores from Nocardia strain acta 3026.
AB  - An actinomycete, strain Acta 3026, isolated from mangrove soil was characterized
      and found to belong to the genus Nocardia. The strain produces two new cytotoxic
      metabolites, nocardichelins A (1) and B (2). Each of the compounds strongly
      inhibited human cell lines from gastric adenocarcinoma, breast carcinoma, and
      hepatocellular carcinoma with GI50 values in a low micromolar to nanomolar range.
      The structural characterization of the compounds was performed by mass
      spectrometry and NMR spectroscopy. The nocardichelins represent a new group of
      siderophores that combine the structural elements of mycobactin-type siderophores
      from mycobacteria and hydroxamate-type siderophores (desferrioxamine B) produced
      by streptomycetes. The chromazurol S assay, characteristic for iron(III)
      complexation, was positive, confirming the role as a siderophore.

PMID- 17536857
TI  - Merodrimanes and other constituents from Talaromyces thailandiasis.
AB  - Chemical study of a previously undescribed fungus, Talaromyces thailandiasis,
      furnished the two new merodrimanes thailandolides A (1) and B (2), an O
      methylated derivative (3) of the aromatic fragment incorporated in thailandolide
      B, and three known closely related 1(3H)-isobenzofuran derivatives,
      penisimplicissin (4a), vermistatin (4b), and hydroxydihydrovermistatin (4c).
      Structures were established by spectroscopic measurements and confirmed by X-ray
      analyses of compounds 1 and 4b. The unusual peptide analogue N
      benzoylphenylalanyl-N-benzoylphenyl alaninate (5) isolated earlier from a higher
      plant was also found.

PMID- 17536858
TI  - Stilbenes from the Orchid Phragmipedium sp.
AB  - Three species of Phragmipedium (Orchidaceae), P. calurum, P. longifolium, and P.
      hybrid (var. Sorcerer's Apprentice), were analyzed by high-throughput isolation.
      A total of 12 new (1-4, 6-10, 12, 14, 16) and five known compounds (5, 11, 13,
      15, 17) were isolated from these orchids. Compounds 1-8 are stilbenes substituted
      with one or two 4-hydroxybenzyl moieties. This type of substitution on stilbenes
      is unusual and has been reported only twice. The structure elucidation was based
      on spectroscopic analysis.

PMID- 17536859
TI  - Isolation of glycosidase-inhibiting hyacinthacines and related alkaloids from
      Scilla socialis.
AB  - An examination of the bulbs of Scilla socialis has resulted in the isolation of
      11 hyacinthacines, two pyrrolidines, and three piperidines. The structures of the
      new alkaloids were elucidated by spectroscopic methods as beta-1-C
      ethyldeoxymannojirimycin (5), hyacinthacines B7 (10), C2 (11), C3 (12), C4 (13),
      and C5 (14), and alpha-5-C-(3-hydroxybutyl)hyacinthacine A2 (15). Although, beta
      l-homofuconojirimycin (3) and alpha-7-deoxyhomonojirimycin (alpha-7-deoxy-HNJ, 4)
      are previously known alkaloids, this is the first report of their occurrence in
      the plant family Hyacinthaceae. Alkaloid 11 was found to be a good inhibitor of
      bacterial beta-glucosidase and human placenta alpha-l-fucosidase, with IC50
      values of 13 and 17 microM, respectively, while alkaloid 12 showed no inhibitory
      activity toward alpha-l-fucosidase but was a more potent inhibitor of bovine
      liver beta-galactosidase (IC50 = 52 microM) than 11. Alkaloids 13 and 14 were
      shown to be inhibitory toward mammalian alpha-glucosidase (IC50 = 45 and 77
      microM, respectively), and alkaloid 14 was demonstrated as a moderate inhibitor
      of bacterial beta-glucosidase (IC50 = 48 microM).

PMID- 17536861
TI  - N,N-Di(4-halophenyl)nitrenium ions: nucleophilic trapping, aromatic substitution,
      and hydrogen atom transfer.
AB  - The reactive intermediates N,N-di(4-chlorophenyl)nitrenium ion and N,N-di(4
      bromophenyl)nitrenium ion were generated through photolysis of the corresponding
      N-amino(2,4,6,-collidinium) ions. The behavior of these diarylnitrenium ions was
      characterized by laser flash photolysis, analysis of the stable photoproducts,
      and ab initio calculations with density functional theory. The latter predict
      these species to have singlet ground states. The halogenated diarylnitrenium ions
      are significantly longer lived than the unsubstituted diphenylnitrenium ion.
      Specifically, cyclization to form carbazole derivatives occurs negligibly, if at
      all, with the halogenated derivatives. They do, however, carry out most of the
      characteristic reactions of singlet arylnitrenium ions, including combining with
      nucleophiles on the aryl rings, adding to arenes, and accepting electrons from
      readily oxidized traps. Interestingly these species also abstract H atoms from
      1,4-cyclohexadiene and various phenol derivatives. The implication of the latter
      process in relation to the computed singlet-triplet energy gaps of ca. -12.5
      kcal/mol is discussed.

PMID- 17536862
TI  - Reversal phenomenon of reaction velocity in a mixed reaction system: silylations
      between simple alcohols and alpha- or beta-hydroxyketones using anilinosilanes
      and catalytic TBAF agent.
AB  - We encountered a unique phenomenon of reaction velocity reversal during the
      silylation between mixed simple alcohols (A; AOH) and alpha- or beta
      hydroxyketones (B; BOH). The present reaction system using anilinosilanes 1a
      [PhNH(TMS)] (TMS-A) and 1b [PhNH(TES)] (TES-A) with the catalytic TBAF (0.02
      equiv) reagent showed that the order of silylation-velocity between the
      independent system and the mixed system was distinctively reversed [nu(A) > nu(B)
      approximately nu(B(mix)) > nu(A(mix))]. A total of seven examples indicate its
      high generality: AOH = linalool, 3-octanol; BOH = valeroin, benzoin, 5-hydroxy-4
      methyl-3-undecanone. Time-dependent IR spectroscopy analysis rationally supported
      this speculation.

PMID- 17536863
TI  - Tuning of the prolyl trans/cis-amide rotamer population by use of C
      glucosylproline hybrids.
AB  - We describe the synthesis of a fused bicyclic C-glucosylproline hybrid (GlcProH)
      from commercially available 2,3,4,6-tetra-O-benzyl-d-glucopyranose. The GlcProH
      was incorporated into the model peptides Ac-GlcProH-NHMe and Ac-Gly-GlcProH-NHMe.
      Postsynthetic modifications can be introduced via derivatization of the
      carbohydrate scaffold. Conformational analysis of the GlcProH-modified model
      peptides shows that while the conformation of GlcProH remains fixed, the prolyl N
      terminal amide equilibrium (Kt/c) can be varied with different modifications of
      the carbohydrate scaffold. Simple N-acyl derivatives studied by NMR spectroscopy
      showed that in CD3OD there was an increase in the cis-amide content as the sugar
      substituents changed from benzyl (10%) to hydroxyl (22%) to acetate (36%).
      Similar effects were observed in DMSO-d6. The exact nature of the influence is
      unclear, but it most likely arises through intramolecular interactions between
      sugar groups and the peptidic amide backbone. Overall, our GlcProH demonstrates
      variation in Kt/c through tuning of the carbohydrate scaffold: a new concept in
      proline peptidomimetics.

PMID- 17536864
TI  - Preparation of N-alkylbis(3-aminopropyl)amines by the catalytic hydrogenation of
      N-alkylbis(cyanoethyl)amines.
AB  - An improved process for the preparation of N-alkylbis(3-aminopropyl)amines is
      described. These triamines are of interest as monomers for the condensation
      polymerization with esterified carbohydrate diacids (aldaric acids) to generate
      the corresponding poly(4-alkyl-4-azaheptamethylene aldaramides). The triamine
      synthesis is comprised of two efficient steps and requires no chromatographic
      purification. Bisconjugate addition of alkylamines to acrylonitrile followed by
      catalytic hydrogenation of the N-alkylbis(cyanoethyl)amines over Raney nickel
      yields the target N-alkylbis(3-aminopropyl)amines. Much less solvent was used in
      the bisconjugate addition step then previously reported, and in the second step,
      a relatively low-pressure catalytic hydrogenation (50 psi of hydrogen) was
      employed using Raney nickel as the catalyst in a 7 N methanolic ammonia solvent
      system to afford the N-alkylbis(3-aminopropyl)amines of high purity in nearly
      quantitative yield.

PMID- 17536865
TI  - Synthesis and oxidation of triarylamine derivatives bearing hydrogen-bonding
      groups.
AB  - Hydrogen-bonding triarylamines, 4-(N,N-bis(4-methoxyphenyl)amino)benzoic acid
      (TPA1), 5-(N,N-bis(4-methoxyphenyl)amino)isophthalic acid (TPA2), and N-(4-(1H
      benzimidazol-2-yl)phenyl)-N,N-bis(4-methoxyphenyl)amine (BImTPA), were
      synthesized as radical cation precursors. TPA1 and TPA2 are readily p-doped by
      AgSbF(6) to give highly persistent radical cations. Poor solid-state spin yields
      of the radical cation from BImTPA may be due to spin delocalization.

PMID- 17536867
TI  - Parallel synthesis and yeast growth inhibition screening of succinamic acid
      libraries.
AB  - Libraries of succinamic acid derivatives resulting from the condensation of a
      series of succinic acid derivatives with amines are reported as putative
      khafrefungin analogues. A total of 480 compounds derived from the initial
      condensation of 8 scaffolds with 60 different amines have been synthesized using
      automated technology with the help of scavenger resins. A simple acetate
      hydrolysis of five of the above sublibraries afforded additional 300 compounds
      for a total of 780 compounds. Around 55% of the library members showed purities
      higher than 70% (HPLC-ELS-MS) thus proving the generality of this approach.
      Results on growth inhibition of the yeast Saccharomyces cerevisiae in the
      presence of selected library members are also reported as a preliminary
      evaluation of the antifungal activity.

PMID- 17536868
TI  - Characterization of the functional binding properties of antibody conjugated
      quantum dots.
AB  - Antibody conjugated quantum dots are an emerging technology for high-resolution
      labeling of biological systems. In this work we determined the number of
      functional antibodies (i.e., antibodies that are sterically available for
      functional binding to target proteins) conjugated to semiconductor quantum dots.
      This is critical for the interpretation of biological data labeled with these
      methods. We found that the number of available functional antibodies varied
      significantly for different conjugation methods and are lower than previously
      estimated. These results may suggest potential strategies for improving quantum
      dot labeling of biological preparations.

PMID- 17536870
TI  - Clinical pharmacology study of Bramitob, a tobramycin solution for nebulization,
      in comparison with Tobi.
AB  - BACKGROUND AND OBJECTIVES: To compare in vitro characteristics and
      pharmacokinetics of Bramitob, a preservative-free tobramycin solution for
      nebulization, and Tobi in patients with cystic fibrosis (CF) and Pseudomonas
      aeruginosa infection. METHODS: In vitro characteristics of Bramitob and Tobi were
      evaluated using Pari TurboBoy/LC Plus and the Systam 290 LS nebulizers. In the
      randomized, double-blind, two-way crossover pharmacokinetic study, 11 patients
      with CF received a single nebulized dose (300mg) of Bramitob or Tobi, separated
      by a 7-day washout period. Plasma and sputum tobramycin concentrations were
      measured immediately before and over 24 hours after administration. RESULTS:
      Bramitob and Tobi performed alike during nebulization. The fine particle fraction
      was 33-37% and the mass median aerodynamic diameter was <5microm. Nine patients
      completed the pharmacokinetic study. Tobramycin plasma profiles after
      administration of Bramitob or Tobi were similar, with a peak at 90 and 72 minutes
      after inhalation of Bramitob and Tobi, respectively. The elimination half-life
      was ~5 hours for both products. The relative bioavailability of Bramitob to Tobi
      was 1.01, indicating comparable systemic exposure. Peak sputum concentration of
      tobramycin was 816 +/- 681 microg/g for Tobi and 1289 +/- 851 microg/g for
      Bramitob and was >400 microg/g (threshold sufficient for an antibacterial effect
      against P. aeruginosa) in 5 out of 9 patients receiving Tobi and 8 out of 9
      patients receiving Bramitob. All adverse events were considered mild and judged
      not related to the study drugs. CONCLUSIONS: In vitro performance of
      Bramitob((R)) was similar when nebulized with Pari TurboBoy k/LC Plus and Systam
      290 LS nebulizers and comparable to that of TobiThe systemic bioavailability of
      tobramycin was similar after administration of either Bramitob or Tobi; however,
      in sputum samples the tobramycin peak concentration was slightly greater after
      administration of Bramitob than after Tobi.

PMID- 17536871
TI  - Efficacy, safety, and local pharmacokinetics of highly concentrated nebulized
      tobramycin in patients with cystic fibrosis colonized with Pseudomonas
      aeruginosa.
AB  - BACKGROUND AND AIM: Progressive respiratory failure due to Pseudomonas aeruginosa
      colonization is the most significant morbidity in patients with cystic fibrosis
      (CF). This trial was designed to investigate the efficacy and safety of a highly
      concentrated (300mg/4mL) tobramycin solution for inhalation (TSI) [Bramitob] in
      patients with CF and P. aeruginosa infection. METHODS: Fifty-nine patients were
      randomized to receive a 4-week treatment with tobramycin or placebo administered
      twice daily via the Pari LC Plus nebulizer and Pari TurboBoy compressor, followed
      by a 4-week run-out phase. Pulmonary function (forced expiratory volume in 1
      second [FEV(1)], forced vital capacity [FVC], and forced expiratory flow at the
      midportion of vital capacity [FEF(25-75%)]), P. aeruginosa susceptibility,
      microbiologic results, and in vitro minimum inhibitory concentration for 90% of
      strains (MIC(90)) were the efficacy outcome measures, while safety was monitored
      by the recording of adverse events, audiometry (bone conduction at 250-8,000Hz
      frequency), laboratory tests, physical examination and general health condition.
      The concentration of tobramycin attained in sputum was measured in a cohort of 21
      patients. RESULTS: FEV(1) significantly increased from baseline in the tobramycin
      group compared with no change in the placebo group: the absolute difference
      between groups (intent-to-treat population) of predicted normal was 13.2% at week
      2 (p = 0.002) and 13.3% at week 4 (p = 0.003). Significant differences in favor
      of the tobramycin group were also observed for FVC and FEF(25-75%). The
      microbiologic results at the end of the treatment period (P. aeruginosa-negative
      culture, persistence, superinfection) showed a significantly better outcome in
      the tobramycin group compared with placebo (p = 0.033). The effects of tobramycin
      on pulmonary function and microbiology were not maintained at the end of the run
      out phase. Mean sputum concentrations of tobramycin after the first dose (695.6
      +/- 817.0 microg/mL) were similar to those measured after the last dose (716.9 +/
      799 microg/mL) and were superior to the detected specific MIC(90). The
      proportion of patients with drug-related adverse events was lower in the
      tobramycin group and no signs of renal or auditory toxicity were observed.
      CONCLUSIONS: The 4-week administration of a highly concentrated TSI significantly
      improved pulmonary function and microbiologic outcome compared with placebo and
      was well tolerated. The results of this study should be confirmed in further long
      term trials in larger populations.

PMID- 17536872
TI  - A formulation of aerosolized tobramycin (Bramitob) in the treatment of patients
      with cystic fibrosis and Pseudomonas aeruginosa infection: a double-blind,
      placebo-controlled, multicenter study.
AB  - BACKGROUND AND AIM: Chronic infection with Pseudomonas aeruginosa in patients
      with cystic fibrosis (CF) causes progressive deterioration in lung function. The
      purpose of this trial was to assess the efficacy and tolerability of a tobramycin
      highly concentrated solution for inhalation (TSI) [300mg/4mL; Bramitob when added
      to other antipseudomonal therapies in CF patients with chronic P. aeruginosa
      infection. METHODS: In a multinational, double-blind, multicenter study, CF
      patients with chronic P. aeruginosa infection were randomized to receive
      nebulized tobramycin or placebo over a 24-week study period in which 4-week
      treatment periods ('on' cycles) were followed by 4-week periods without treatment
      ('off' cycles). Forced expiratory volume in 1 second (FEV(1)) percentage of
      predicted normal was used as the primary efficacy outcome parameter. Forced vital
      capacity (FVC), forced expiratory flow at 25-75% of FVC (FEF(25)(-)(75%)), P.
      aeruginosa susceptibility, minimum concentration required to inhibit 90% of
      strains (MIC(90)), rates of P. aeruginosa-negative culture, P. aeruginosa
      persistence and superinfection, need for hospitalization and parenteral
      antipseudomonal antibiotics, loss of school/working days due to the disease, and
      nutritional status (bodyweight and body mass index) were considered as secondary
      efficacy outcome parameters. Adverse events reporting, audiometry, and renal
      function were monitored to evaluate the tolerability and safety of TSI. RESULTS:
      A total of 247 patients were randomized in the study. At endpoint time assessment
      (week 20), FEV(1) was significantly increased in the tobramycin group and the
      adjusted mean difference between groups (intention-to-treat population) was
      statistically significant (p < 0.001). At the same time, clinically relevant
      improvements in FVC and FEF(25-75%) were detected in the TSI group (p = 0.022 and
      p = 0.001, respectively). The microbiologic outcomes at the end of the last 'on'
      cycle period were significantly better in the TSI group than the placebo group (p
      = 0.024), although there was a concomitant trend toward an increase in the MIC of
      isolated P. aeruginosa strains. The percentage of patients hospitalized as well
      as the need for parenteral antipseudomonal antibiotics was significantly lower in
      the TSI group (p = 0.002 and p = 0.009, respectively). Patients treated with TSI
      had fewer lost school/working days due to the disease (p < 0.001). A favorable
      effect of tobramycin in terms of an increase in bodyweight and body mass index
      was also noted, when compared with placebo, at all time points (p < 0.01 and p <
      0.001, respectively). No significant changes in serum creatinine and auditory
      function were detected. The proportion of patients with drug-related adverse
      events was 15% in both treatment groups. CONCLUSIONS: Long-term, intermittent
      administration of this aerosolized tobramycin formulation (300mg/4mL) in CF
      patients with P. aeruginosa chronic infection significantly improved pulmonary
      function and microbiologic outcome, decreased hospitalizations, increased
      nutritional status, and was well tolerated.

PMID- 17536873
TI  - The National e-Prescribing Patient Safety Initiative: removing one hurdle,
      confronting others.

PMID- 17536874
TI  - Impact of restricting paracetamol pack sizes on paracetamol poisoning in the
      United Kingdom: a review of the literature.
AB  - Paracetamol (acetaminophen) is the most common drug taken in overdose in the UK,
      accounting for 48% of poisoning admissions to hospital and being involved in an
      estimated 100-200 deaths per year. In 1998, the UK government introduced
      legislation that reduced the maximum pack size of all non-effervescent tablets
      and capsules containing aspirin (acetylsalicylic acid) or paracetamol that can be
      sold or supplied from outlets other than registered pharmacies from 25 to 16
      tablets or capsules. This article reviews the literature to determine the
      effectiveness of the legislation, focusing specifically on paracetamol poisoning.
      Seventeen studies on this subject were identified. Three studies found reductions
      in mortality rates; one study found an increase in mortality rates, while one
      found an initial reduction followed by an eventual increase; three found no
      significant difference in mortality rates before and after introduction of the
      legislation. Five studies found reductions in admissions to liver units, three of
      these finding a reduction in liver transplantation rates; two further studies
      found no change in liver function tests and rates of paracetamol-induced acute
      liver injury or failure. Four studies found a sustained decrease in hospital
      admissions, while two found an initial decrease followed by an eventual increase.
      One study found a decline in admissions for paracetamol poisoning and an increase
      in admissions for non-paracetamol poisoning. Sales data are conflicting, with two
      studies finding no significant difference in paracetamol sales before and after
      the introduction of the legislation and one reporting a decline. The severity of
      overdose appears to have decreased since the maximum permitted packet size was
      reduced, with five studies reporting a reduction in the number of severe
      overdoses (measured by numbers of tablets ingested, serum paracetamol
      concentrations and usage of antidotes). Only two studies reported an increase in
      the number of severe overdoses.Paracetamol-associated mortality rates, admissions
      to liver units/liver transplants, hospital admissions and the severity of
      paracetamol overdose appear to have been decreasing since 1998. However, one
      study showed that the reductions in mortality and hospital admissions began in
      1997; therefore, the contribution of the 1998 legislation to the observed changes
      is unclear. Most of the studies are based on short-term follow-up so it is
      difficult to draw any conclusions regarding long-term trends. Many of the studies
      were also restricted to relatively small areas of the UK; this, combined with a
      variety of outcome measures, makes it difficult to distinguish any conclusive
      trends. The studies also suffer from a lack of comparison and control groups.
      Some studies do not clearly differentiate between the paracetamol preparations
      covered by the legislation and those not. The limited number of studies to date,
      combined with a variety of outcome measures, make it difficult to determine with
      accuracy whether or not the legislation has been a success. More long-term
      studies are needed to fully assess the impact of the legislation.

PMID- 17536875
TI  - Safety and toxicity of sulfadoxine/pyrimethamine: implications for malaria
      prevention in pregnancy using intermittent preventive treatment.
AB  - Plasmodium falciparum infection during pregnancy is strongly associated with
      maternal anaemia and low birth weight, contributing to substantial morbidity and
      mortality in sub-Saharan Africa. Intermittent preventive treatment in pregnancy
      with sulfadoxine/pyrimethamine (IPTp-SP) has been one of the most effective
      approaches to reduce the burden of malaria during pregnancy in Africa. IPTp-SP is
      based on administering >or=2 treatment doses of sulfadoxine/pyrimethamine to
      pregnant women at predefined intervals after quickening (around 18-20 weeks).
      Randomised, controlled trials have demonstrated decreased rates of maternal
      anaemia and low birth weight with this approach. The WHO currently recommends
      IPTp-SP in malaria-endemic areas of sub-Saharan Africa. However, implementation
      has been suboptimal in part because of concerns of potential drug toxicities.
      This review evaluates the toxicity data of sulfadoxine/pyrimethamine, including
      severe cutaneous adverse reactions, teratogenicity and alterations in bilirubin
      metabolism. Weekly sulfadoxine/pyrimethamine prophylaxis is associated with rare
      but potentially fatal cutaneous reactions. Fortunately, sulfadoxine/pyrimethamine
      use in IPTp programmes in Africa, with 2-4 treatment doses over 6 months, has
      been well tolerated in multiple IPTp trials. However, sulfadoxine/pyrimethamine
      should not be administered concurrently with cotrimoxazole given their redundant
      mechanisms of action and synergistic worsening of adverse drug reactions.
      Therefore, HIV-infected pregnant women in malaria endemic areas who are already
      receiving cotrimoxazole prophylaxis should not also receive IPTp-SP. Although
      folate antagonist use in the first trimester is associated with neural tube
      defects, large case-control studies have demonstrated that
      sulfadoxine/pyrimethamine administered as IPTp (exclusively in the second and
      third trimesters and after organogenesis) does not result in an increased risk of
      teratogenesis. Folic acid supplementation is recommended for all pregnant women
      to reduce the rate of congenital anomalies but high doses of folic acid (5
      mg/day) may interfere with the antimalarial efficacy of
      sulfadoxine/pyrimethamine. However, the recommended standard dose of folic acid
      supplementation (0.4 mg/day) does not affect antimalarial efficacy and may
      provide the optimal balance to prevent neural tube defects and maintain the
      effectiveness of IPTp-SP. No clinical association between
      sulfadoxine/pyrimethamine use and kernicterus has been reported despite the
      extensive use of sulfadoxine/pyrimethamine and related compounds to treat
      maternal malaria and congenital toxoplasmosis in near-term pregnant women and
      newborns. Although few drugs in pregnancy can be considered completely safe,
      sulfadoxine/pyrimethamine - when delivered as IPTp - has a favourable safety
      profile. Improved pharmacovigilance programmes throughout Africa are now needed
      to confirm its safety as access to IPTp-SP increases. Given the documented
      benefits of IPTp-SP in malaria endemic areas of Africa, access to this treatment
      for pregnant women should continue to expand.

PMID- 17536876
TI  - Incidence and nature of medication errors in neonatal intensive care with
      strategies to improve safety: a review of the current literature.
AB  - Neonates are highly vulnerable to medication errors because of their extensive
      exposure to medications in the neonatal intensive care unit (NICU), the general
      lack of evidence on pharmacotherapeutic interventions in neonates and the lack of
      neonate-specific formulations. We searched PubMed and EMBASE to identify relevant
      original studies published in the English language. Eleven studies were
      identified on the frequency of medication errors in the NICU. The highest rate
      was 5.5 medication errors per 100 prescriptions; however, medication error rates
      varied widely between studies, partly due to differences in the definition of an
      error and the rigor of the method used to identify medication errors.
      Furthermore, studies were difficult to compare because medication error rates
      were calculated differently. Most studies did not assess the potential clinical
      impact of the errors. The majority of studies identified dose errors as the most
      common type of error. Computerised physician order entry and interventions by
      clinical pharmacists (e.g. the participation of pharmacists in ward rounds and
      review of patients' prescriptions prior to dispensing) were the most common
      interventions suggested to improve medication safety in the NICU. However, only
      very limited data were available on evaluation of the effects of such
      interventions in NICUs. More research is needed to determine the frequency and
      types of medication errors in NICUs and to develop evidence-based interventions
      to improve medication safety in the NICU setting. Some of these research efforts
      need to be directed to the establishment of clear definitions of medication
      errors and agreement on the methods that should be used to measure medication
      error rates and their potential clinical impact.

PMID- 17536877
TI  - Statins, neuromuscular degenerative disease and an amyotrophic lateral sclerosis
      like syndrome: an analysis of individual case safety reports from vigibase.
AB  - BACKGROUND: The WHO Foundation Collaborating Centre for International Drug
      Monitoring (Uppsala Monitoring Centre [UMC]) has received many individual case
      safety reports (ICSRs) associating HMG-CoA reductase inhibitor drug (statin) use
      with the occurrence of muscle damage, including rhabdomyolysis, and also
      peripheral neuropathy. A new signal has now appeared of disproportionally high
      reporting of upper motor neurone lesions. AIM AND SCOPE: The aim of this paper is
      to present the upper motor neurone lesion cases, with other evidence, as a signal
      of a relationship between statins and an amyotrophic lateral sclerosis (ALS)-like
      syndrome. The paper also presents some arguments for considering that a spectrum
      of severe neuromuscular damage may be associated with statin use, albeit rarely.
      The paper does not do more than raise the signal for further work and analysis of
      what must be regarded as a potentially very serious and perhaps avoidable or
      reversible adverse reaction, though it also suggests action to be taken if an ALS
      like syndrome should occur in a patient using statins. METHODS: The 43 reports
      accounting for the disproportional reports in Vigibase (the database of the WHO
      Programme for International Drug Monitoring) are summarised and analysed for the
      diagnosis of an ALS-like syndrome. The issues of data quality and potential
      reporting bias are considered. RESULTS: 'Upper motor neurone lesion' is a rare
      adverse event reported in relationship to drugs in Vigibase (a database
      containing nearly 4 million ICSRs). Of the total of 172 ICSRs on this reported
      term, 43 were related to statins, of which 40 were considered further: all but
      one case was reported as ALS. In 34/40 reports a statin was the sole reported
      suspected drug. The diagnostic criteria were variable, and seven of the statin
      cases also had features of peripheral neuropathy. Of a total of 5534 ICSRs of
      peripheral neuropathy related to any drug in Vigibase, 547 were on statins. The
      disproportional reporting of statins and upper motor neurone lesion persisted
      after age stratification, and such disproportionality was not seen for statins
      and Parkinson's disease, Alzheimer's disease, extrapyramidal disorders, or
      multiple sclerosis-like syndromes. DISCUSSION: Because the cases were sometimes
      atypical we propose the use of the term 'ALS-like syndrome' and speculate whether
      this is part of a spectrum of rare neuromuscular damage. The diagnosis of ALS is
      often problematic, and the insidiousness and chronicity of the disease make
      causality with a drug difficult to assess. The disproportionally high reporting
      makes this an important signal nevertheless, since ALS is serious clinically and
      statins are so widely used. Wide use of the statins also makes a chance finding
      more probable, but is unlikely to cause disproportional reporting when there are
      no obvious biases identified. CONCLUSION: We emphasise the rarity of this
      possible association, and also the need for further study to establish whether a
      causal relationship exists. We do advocate that trial discontinuation of a statin
      should be considered in patients with serious neuromuscular disease such as the
      ALS-like syndrome, given the poor prognosis and a possibility that progression of
      the disease may be halted or even reversed.

PMID- 17536878
TI  - Gynaecomastia associated with proton pump inhibitors: a case series from the
      Spanish Pharmacovigilance System.
AB  - OBJECTIVE: Proton pump inhibitors (PPIs) are widely used in the management of
      peptic ulcer and related symptoms. They have been linked to certain endocrine
      adverse reactions, including gynaecomastia. The aim of the present study is to
      investigate the association between the use of PPIs and the development of
      gynaecomastia. METHODS: Reports of cases of gynaecomastia that had putatively
      been induced by PPIs and that had been collected by the Spanish Pharmacovigilance
      System via the 'yellow card' scheme, were analysed. Reporting odds ratios (RORs)
      were calculated as a measure of disproportionality. RESULTS: Twenty-four cases of
      gynaecomastia associated with PPIs were identified in the database of the Spanish
      Pharmacovigilance System. Overall, there was a clear temporal sequence of events
      in all cases and the adverse effect disappeared after drug withdrawal in most of
      the cases; 14 patients were also receiving other drugs at the time of the adverse
      effect. The ROR for omeprazole exposure versus no exposure, but not that for
      other PPIs, showed a statistically significant elevation (ROR adjusted for age
      5.23; 95% CI 3.32, 8.26). CONCLUSION: Considering the widespread use of PPIs,
      gynaecomastia may affect a large number of patients. In most cases, the condition
      seems to be reversible with drug withdrawal. Doctors should be aware of this
      potential adverse reaction when prescribing PPIs to their patients over long
      periods of time.

PMID- 17536879
TI  - Surveillance of prescription drug-related mortality using death certificate data.
AB  - BACKGROUND: The prescription drugs or drug classes that are most frequently
      associated with death in the US might be identifiable from death certificate
      data. OBJECTIVE: To identify the drugs/drug classes associated with the greatest
      numbers of deaths in the US that might be considered as possible targets for
      prevention. STUDY DESIGN: US vital statistics data were accessed in order to
      identify International Classification of Diseases (10th Revision) [ICD-10] codes
      indicating that prescription drugs had caused or contributed to death and
      diseases with significant drug-related mortality. MAIN OUTCOME MEASURE: ICD-10
      codes for primarily prescription drugs that were listed as the underlying cause
      or as 'total mentions' on death certificates and were implicated in >or=1000
      deaths in any one year were selected. The annual number of deaths by ICD-10 code
      was obtained from the Division of Vital Statistics, National Center for Health
      Statistics. Codes for diseases with significant drug-related aetiologies and
      involvement in >or=1000 deaths in any one year were also identified and analysed
      separately. RESULTS: For the selected ICD-10 codes, a total of 25 031 deaths were
      listed as having a prescription drug as the underlying cause in 2003, compared
      with 16 135 in 1999, a 55% increase. Total mentions of these codes increased from
      46 523 in 1999 to 72 080 in 2003, also a 55% increase. Most codes involved
      'poisonings' (overdose or the wrong substance given or taken in error that is
      accidental, intentional or with undetermined intent). Drugs associated with
      poisoning deaths had central nervous system effects. Among the codes associated
      with specified drug classes, poisonings and accidental poisonings involving
      narcotics, hallucinogens, psychoactive substances and opioids (other than opium
      and heroin) were associated with the largest numbers of deaths. Drug-related
      codes associated with the largest percentage increases in deaths between 1999 and
      2003 included poisoning due to methadone (275%); poisoning by other and
      unspecified antidepressants (primarily selective serotonin reuptake inhibitors)
      [130%]; and poisoning by psychostimulants with potential for abuse (amfetamines
      and drugs for attention deficit hyperactivity disorder) [117%]. Anticoagulants
      were associated with the largest numbers of deaths with codes involving "adverse
      effects in therapeutic use". Among diseases with significant drug-related
      aetiologies, Clostridium difficile enterocolitis (associated primarily with
      antibacterials) had the largest percentage increase in total mentions, with a
      203% rise between 1999 and 2003. CONCLUSIONS: Deaths due to overdoses are the
      most prominent cause of drug-related mortality in death certificate data. Certain
      drugs and drug classes, especially the opioids (e.g. narcotics, methadone),
      psychoactive drugs (e.g. antidepressants, amfetamines), anticoagulants and
      antibacterials (which cause or contribute to C. difficile enterocolitis) are
      associated with large and increasing numbers of deaths and preventive strategies
      should be considered.

PMID- 17536880
TI  - Discontinuation of beta-blockers and the risk of myocardial infarction in the
      elderly.
AB  - BACKGROUND: It has been shown that the abrupt cessation of treatment with beta
      adrenoceptor antagonists (beta-blockers) increases the risk of myocardial
      infarction in patients with hypertension. As beta-blockers differ in their
      pharmacokinetic and pharmacodynamic properties, this risk of discontinuation
      might also differ between subgroups of beta-blockers. OBJECTIVE: To determine
      whether discontinuation of beta-blockers is associated with an increased risk of
      myocardial infarction in elderly patients and whether the effects of recent
      cessation differs between subgroups of beta-blockers, categorised according to
      their selectivity, lipophilic profile and intrinsic sympathomimetic activity
      (ISA). DESIGN: A cohort study in users of beta-blockers within the Rotterdam
      Study, which was a prospective population-based follow-up study of 7983
      individuals aged >or=55 years. PATIENTS: We identified 2588 individuals who had
      been treated with a beta-blocker for at least 30 days at any time during the
      study period of 1 January 1991 to 1 January 2002. In this group, 148 subjects
      developed incident myocardial infarction. METHODS: Detailed information on the
      medication use and clinical characteristics of all patients were collected from
      the files of pharmacies, general practices and hospitals. Myocardial infarction
      was diagnosed on the basis of internationally accepted criteria and verified by a
      cardiologist. The duration of beta-blocker use was calculated from computerised
      pharmacy records on the basis of the number of dispensed tablets or capsules and
      the prescribed daily number. For every individual, on the index date (date of
      myocardial infarction in cases, the same date in controls [defined as any patient
      who had not experienced a myocardial infarction up to that timepoint]) the usage
      of beta-blockers was determined and classified as either current or as past use.
      Past use was classified into three different periods: cessation of beta-blockers
      less than 30 days; between 30 and 180 days; and more than 180 days before the
      index date. The risk of myocardial infarction in the three periods of cessation
      of exposure were analysed using a Cox proportional hazards model that included
      potential confounders and cardiac co-medication. These analyses were performed
      for the whole group and for subgroups of beta-blockers. RESULTS: Discontinuation
      of any beta-blocker was not associated with an increased risk of myocardial
      infarction compared with current use of a beta-blocker. Analyses within subgroups
      showed that discontinuation of selective beta-blockers was associated with an
      increased risk of myocardial infarction compared with current use of any beta
      blocker within the first 30 days (relative risk [RR] 2.70; 95% CI 1.06, 6.89) and
      also between 30 and 180 days after discontinuation (RR 2.44; 95% CI 1.07, 5.59).
      No increased risk was demonstrated in the other beta-blocker subgroups.
      CONCLUSION: Overall, discontinuation of beta-blockers was not associated with an
      increased risk of myocardial infarction. However, when analysed by beta-blocker
      subgroup, cessation of selective beta-blockers was associated with an increased
      risk of myocardial infarction during the first 180 days after discontinuation.

PMID- 17536881
TI  - 'Extreme duplication' in the US FDA Adverse Events Reporting System database.

PMID- 17536882
TI  - Efficacy of UFT plus Tamoxifen for Estrogen-Receptor-Positive Breast Cancer and
      Tamoxifen plus UFT for Estrogen-Receptor-Negative Breast Cancer : Adjuvant
      Therapy after Administration of Mitomycin.
AB  - OBJECTIVE: We conducted a prospective multicentre, collaborative randomised study
      on postoperative adjuvant therapy in patients with stage II primary breast cancer
      to evaluate the effect of a combination of tegafur and uracil (UFT) on tamoxifen
      (TAM) plus mitomycin (MM) in patients with estrogen-receptor-positive [ER(+)]
      breast cancer and TAM on UFT + MM in patients with estrogen-receptor-negative
      [ER(-)] breast cancer. METHODS: MM (13 mg/m(2)) was intravenously administered on
      the day of surgery for all patients, after which patients with ER(+) were
      randomised to TAM 20 mg/day (treatment A) or TAM 20 mg/day and UFT 400 mg/day
      (treatment B). Patients who were ER(-) were randomly allocated UFT 400 mg/day
      (treatment C) or TAM 20 mg/day and UFT 400 mg/day (treatment D). TAM and UFT were
      administered orally for 2 years, starting on day 14 after surgery. ENDPOINTS: 5
      year disease-free survival (5y DFS), 5-year overall survival (5y OS), and safety.
      RESULTS: The study commenced in November 1988 and the data cut-off was May 1997
      after follow-up of the last patient for 5 years. A total of 765 patients with
      stage II breast cancer were enrolled. 436 patients with ER(+) [group A: 213,
      group B: 223] and 317 patients with ER(-) [group C: 162, group D: 155] breast
      cancer were eligible for this study. The rate of 5y DFS was 83.1% for group A and
      90.7% for group B (p = 0.020). There was a significant difference in 5y DFS
      between the two groups among postmenopausal and positive lymph node metastases
      patients. The incidence of adverse reactions was 4% for group A and 18% for group
      B (p < 0.05). The rate of 5y DFS was 77.1% for group C and 85.5% for group D (p =
      0.063). The rate of 5y OS was 84.7% for group C and 89.8% for group D (p =
      0.216). The incidence of adverse reactions was 18% in group C and 11% in group D
      (p = 0.06). CONCLUSION: UFT in combination with TAM + MM showed higher efficacy
      than TAM + MM as a postoperative combination therapy for breast cancer in
      patients with ER(+) breast cancer. A trend was observed in favour of the addition
      of TAM to UFT + MM in postmenopausal and lymph node metastases-negative patients
      with ER(-) breast cancer.

PMID- 17536883
TI  - Intramuscular Etofenamate versus Diclofenac in the Relief of Renal Colic : A
      Randomised, Single-Blind, Comparative Study.
AB  - OBJECTIVE: To compare the efficacy and adverse effects of intramuscular
      etofenamate and intramuscular diclofenac in the relief of acute renal colic.
      PATIENTS AND METHODS: A multicentre, randomised, single-blind study was performed
      in 119 patients admitted to the emergency room for renal colic. Patients were
      assigned to treatment with either etofenamate 1000mg or diclofenac 75mg, both
      administered intramuscularly. Pain was self-assessed using a 4-point verbal
      rating scale (VRS) and a visual analogue scale (VAS) just before drug
      administration and 30, 60, 120 and 240 min later. RESULTS: The two groups were
      similar with regard to baseline characteristics. The percentages of patients who
      reported an improvement in the VRS at 60 min post-administration (primary
      variable) were 84.5% with etofenamate and 83.3% with diclofenac (p = 0.73). At
      the other timepoints (30, 120 and 240 min), the proportions of patients improved
      were, respectively, 69.5%, 82.6% and 79.3% in the etofenamate group, and 75.0%,
      81.7% and 80.0% in the diclofenac group. The VAS score showed a statistically
      significant improvement in both groups, but no differences between groups were
      found.Analgesic rescue medication was required by 11 (18.6%) patients in the
      etofenamate group and by 12 (20.0%) patients in the diclofenac group. Mild to
      moderate adverse events were reported by 3.4% of patients receiving etofenamate
      and by 5.0% of patients receiving diclofenac. CONCLUSION: Etofenamate and
      diclofenac were similarly effective and tolerated in the relief of acute renal
      colic.

PMID- 17536884
TI  - Renal safety of intravenous ibandronic Acid in breast cancer patients with
      metastatic bone disease.
AB  - INTRODUCTION: Renal adverse events are a troublesome complication of
      bisphosphonate therapy. This study investigated the effect of intravenous
      ibandronic acid (ibandronate) treatment on renal function in breast cancer
      patients with metastatic bone disease. METHODS: 74 patients were randomised to
      double-blind (but not dose-blind) treatment with bolus injections of ibandronic
      acid 2mg (n = 23), 1-hour infusions of ibandronic acid 6mg (n = 28), or placebo
      injections or infusions (n = 23). According to randomisation, patients received
      either three injections or three infusions over the 3-month period, one at the
      start and two subsequent doses at 4-weekly intervals. Measurements of urinary
      excretion of total protein, albumin, alpha(1)-microglobulin, N-acetyl-beta-D
      glucosaminidase, haematuria and serum creatinine were performed before, during
      and after treatment. RESULTS: Treatment with ibandronic acid was not associated
      with impairment of renal function; the renal safety profiles of ibandronic acid 2
      and 6mg were similar to that of placebo. Assessments of proteinuria, haematuria,
      enzymuria and serum creatinine indicated that there were no statistically
      significant changes between pre- and post-treatment levels in patients receiving
      ibandronic acid 2 or 6mg or between patients receiving ibandronic acid or
      placebo. Urine parameters varied during treatment in the same range with
      approximately similar frequency in the ibandronic acid and placebo groups.
      CONCLUSIONS: Short-term administration of intravenous ibandronic acid did not
      impair renal function in breast cancer patients with metastatic bone disease.
      Because tolerability profiles vary between bisphosphonates, the lack of renal
      toxicity with ibandronic acid makes the drug an attractive treatment option for
      metastatic bone disease.

PMID- 17536885
TI  - Effects of losartan and delapril on the fibrinolytic system in patients with mild
      to moderate hypertension.
AB  - BACKGROUND AND OBJECTIVES: Angiotensin-converting enzyme (ACE) probably
      influences the fibrinolytic system at a central point by converting angiotensin I
      to angiotensin II, which increases plasminogen activator inhibitor-1 (PAI-1)
      activity. This effect appears to be mediated in humans via the angiotensin II
      type 1 (AT(1)) receptor. The objective of this study was to evaluate, in patients
      with mild to moderate hypertension, the change in tissue plasminogen activator (t
      PA) and PAI-1 plasma levels after treatment with an AT(1)-receptor blocker
      (losartan 50 mg/day) or an ACE inhibitor (delapril 60 mg/day). PATIENTS AND
      METHODS: 30 hypertensive patients and 15 controls were enrolled. Essential
      hypertension was established by a medical history, physical examination and the
      absence of clinical findings suggestive of a secondary form of hypertension.
      Preliminary investigations, routine biochemical tests (including clearance of
      creatinine and oral glucose tolerance test), chest x-ray, standard and 24-hour
      ECG monitoring, M- and B-mode echocardiography and fundus oculi examinations were
      performed. No patients had previously received ACE inhibitors or AT(1)-receptor
      blockers. After a 14-day run-in period with placebo, patients were randomised in
      a double-blind fashion into two groups: 15 patients were randomised to losartan
      50 mg/day (group 1), 15 patients were randomised to delapril 60 mg/day (group 2),
      and 15 healthy subjects were used as controls (group 3). Plasma PAI-1 and t-PA
      antigen were determined by enzyme-linked immunosorbent assay and a photometric
      method at the end of the run-in period and after 6 months of treatment. RESULTS:
      There were no significant differences among the three groups regarding age, sex,
      body mass index and smoking. After 6 months, both groups of patients showed a
      reduction in blood pressure values. The losartan group did not demonstrate
      significant changes in PAI-1 levels (96.52 +/- 23.73 and 99.89 +/- 22.18 mug/L,
      pre- and post-treatment, respectively) or in t-PA antigen levels (26.17 +/- 6.18
      and 27.32 +/- 5.91 mug/L, pre- and post-treatment, respectively). The delapril
      group showed no significant changes in PAI-1 levels (97.73 +/- 25.75 and 86.12 +/
      13.12 mug/L, pre- and post-treatment, respectively), but did show a
      statistically significant difference (p < 0.005) in t-PA antigen levels (25.71 +/
      6.40 and 32.24 +/- 5.31 mug/L, pre- and post-treatment, respectively). The
      losartan group demonstrated significantly higher post-treatment PAI-1 values than
      the delapril group (p = 0.048). CONCLUSION: The study showed that losartan does
      not affect fibrinolytic parameters, while delapril resulted in an insignificant
      reduction in PAI-1 and a significant increase in t-PA levels. Further studies are
      clearly required in order to establish whether these different effects on the
      fibrinolytic system between ACE inhibitors and AT(1)-receptor blockers may have
      clinical relevance.

PMID- 17536886
TI  - Postmarketing surveillance study of the efficacy and tolerability of pioglitazone
      in insulin-resistant patients with type 2 diabetes mellitus in general practice.
AB  - OBJECTIVE: To evaluate the efficacy and tolerability of pioglitazone in patients
      with type 2 diabetes mellitus treated in general practice settings. DESIGN AND
      SETTING: This was a postmarketing surveillance study involving 2537 primary-care
      physicians throughout Germany. PATIENTS AND INTERVENTIONS: A total of 8760
      patients with type 2 diabetes were treated with pioglitazone 15 or 30mg once
      daily and followed for 16 weeks. RESULTS: Treatment with pioglitazone 15 or 30mg
      once daily was associated with a reduction in both fasting plasma glucose (mean
      50.1 mg/dL) and glycosylated haemoglobin (HbA(1c)) [mean 1.4%] compared with
      baseline. The proportion of patients with 'normal' fasting glucose levels (70-110
      mg/dL) increased from 2.3% at baseline to 24.2% at the final evaluation.
      Pioglitazone therapy was associated with a reduction in levels of triglycerides,
      total cholesterol and low-density lipoprotein (LDL)-cholesterol, and an increase
      in levels of high-density lipoprotein (HDL)-cholesterol. The proportion of
      patients at high risk of developing vascular complications decreased
      progressively during pioglitazone therapy according to a number of parameters.
      CONCLUSIONS: Pioglitazone was well tolerated and effective in improving glycaemic
      control and lipid profiles in patients with type 2 diabetes. Pioglitazone may be
      effective in reducing the risk of vascular complications of diabetes.

PMID- 17536887
TI  - Retrospective cohort study of venlafaxine, fluoxetine or sertraline in long-term
      care.
AB  - OBJECTIVE: To describe the effects of venlafaxine, fluoxetine and sertraline
      treatment on mood and behaviour patterns, physical functioning, and tolerability
      issues in a long-term care environment. DESIGN, SETTING AND PARTICIPANTS:
      Retrospective cohort analysis of 257 elderly residents of three long-term care
      facilities in the US who used venlafaxine, fluoxetine or sertraline during a 3
      month period. MAIN OUTCOME MEASURES: Indicators of depression, anxiety and sad
      mood, physical functioning, antidepressant-related adverse events, and the global
      impression of efficacy. RESULTS: The average age of the participants was 80.6
      years. At the 3-month follow-up, more than 85% of the residents recorded no
      change in indicators of depression, anxiety and sad mood or physical functioning,
      and there were no statistically significant differences among the three
      antidepressant drug groups. A marginal improvement in the social interaction
      indicator was observed among residents who received venlafaxine (11%) compared
      with those receiving fluox-etine (3%) or sertraline (2%). Antidepressant-related
      adverse events were infrequent and similar in incidence across the three drug
      groups. CONCLUSIONS: Indicators of mood and functioning of most residents were
      stable over the 3-month period and similar among the venlafaxine, fluoxetine and
      sertraline groups, and no significant differences in the safety profiles of the
      three drugs were recorded.

PMID- 17536888
TI  - Pharmacokinetics and comparative bioavailability of two metformin formulations
      after single-dose administration in healthy subjects.
AB  - OBJECTIVE: To assess the average bioequivalence of two formulations of metformin
      after single-dose administration of each treatment to healthy subjects under
      fasting conditions by assessing the pharmacokinetic measures of systemic exposure
      and evaluating the confidence intervals (CIs) for each pharmacokinetic parameter.
      DESIGN: Randomised, comparative, single-dose, open-label, balanced, two-period,
      two-treatment, crossover study under fasting conditions. PARTICIPANTS: 20 healthy
      volunteers (ten men and ten women) took part in the study. METHODS: Subjects were
      investigated after a single dose of 850mg after a washout period of 7 days.
      Plasma samples were taken at regular time intervals according to the study
      protocol for measuring plasma metformin concentrations. Systemic exposure was
      estimated with the use of pharmacokinetic parameters (area under the curve of the
      plasma drug concentrations from time zero to the last sampling time [AUC(0-36)],
      area under the curve of the plasma drug concentrations from time zero to infinity
      [AUC(0-)(infinity)], time to peak drug concentration [t(max)], partial area under
      the concentration-time curve with a cut-off point at the t(max) of the reference
      product [AUC(p)], peak plasma drug concentration [C(max)], the ratio C(max)/AUC(0
      )(infinity), and mean residence time [MRT]). The point estimates of
      pharmacokinetic parameters (geometric means of the ratios test [T]/reference [R]
      and the 90% CIs for the ratios of geometric means [T]/[R]), estimated by
      parametric and nonpara-metric analysis, were used in the statistical analysis.
      RESULTS: The point estimates and the 90% CIs after parametric analysis of AUC(0
      )(infinity) were 0.98 and (0.96-1.21), and after nonparametric analysis were 1.06
      and (0.95-1.207), respectively. The two drug products were considered to be
      bioequivalent and with significant variability across subjects for the pharmaco
      kinetic parameters AUC(0-36), AUC(0-)(infinity), C(max) and MRT according to
      analysis of variance of log-transformed data. CONCLUSIONS: The two studied
      formulations of metformin were found to be bioequivalent. They showed similar
      extents and rates of absorption and similar exposure. However, analysis of
      variance of logarithmically transformed data revealed significant variability
      among individuals in AUC(0-36), AUC(0-)(infinity) and C(max), making careful
      individualisation of the metformin dosage important.

PMID- 17536889
TI  - Utilisation Pattern of Nonspecific Nonsteroidal Anti-Inflammatory Drugs and COX-2
      Inhibitors in a Local Health Service Unit in Northeast Italy.
AB  - BACKGROUND AND OBJECTIVE: Nonsteroidal anti-inflammatory drugs (NSAIDs) are
      prescribed widely in Italy. They include nonspecific NSAIDs (NS-NSAIDs) and the
      newly marketed cyclo-oxygenase (COX)-2 specific inhibitors (COXIBs) celecoxib and
      rofecoxib. The objective of this study was to describe the prescribing patterns
      for NS-NSAIDs and COXIBs in a local Italian area, analysing an administrative
      database. PATIENTS AND METHODS: We extracted from the database information on
      subjects who had received at least one reimbursed prescription of an NSAID during
      the period between 1 January 2001 and 31 December 2001, including age, sex,
      patient identification code, Anatomical Therapeutic Chemical (ATC) classification
      system code, strength, formulation, number of packs prescribed, prescription
      date, and prescription of gastroprotective agents (GPAs) on the same day as the
      prescription of the NSAID. On the basis of the type of NSAID received, we divided
      the patients into five cohorts: oral NS-NSAIDs only during the observed year,
      injectable NS-NSAIDs only, celecoxib only, rofecoxib only, and a combination. For
      descriptive purposes, we defined three age groups: <40 years, 40-64 years, and
      >64 years. The duration of exposure to NSAID therapy was calculated using the
      most commonly prescribed dose for the different drugs. Subjects receiving >/=30
      doses per year were defined as "regular users". Analyses included mean age, mean
      duration of exposure, percentage of regular users, and percentage of GPAs co
      prescribed in the different cohorts. RESULTS: NSAIDs were prescribed to 62 059
      subjects from a resident population of 365 321 inhabitants; 43.8% received oral
      NS-NSAIDs only, 22.6% injectable NS-NSAIDs only, 7.2% celecoxib only, 5.2%
      rofecoxib only, and 22% different regimens of different types of NSAIDs. The mean
      duration of treatment increased with age in all cohorts; the mean age was 56
      years in the NS-NSAID cohort, 61 years in the celecoxib cohort, and 62 years in
      the rofecoxib cohort (p = 0.01, COXIBs vs NS-NSAIDs). The mean duration of
      therapy was 11.4 days/year for injectable NS-NSAIDs, 43.8 days/year for
      rofecoxib, 50.5 days/year for oral NS-NSAIDs, and 53.7 days/year for celecoxib.
      Fifty-four percent of subjects in the oral NS-NSAID cohort were regular users
      versus 64% in the rofecoxib and 70% in the celecoxib groups (p = 0.001, COXIBs vs
      NS-NSAIDs). Co-prescription with GPAs was 9.5% for NS-NSAIDs, 8.4% for rofecoxib,
      and 7.7% for celecoxib. CONCLUSIONS: Analysis of an administrative database in
      Italy showed a trend suggesting that COXIBs are prescribed to an older population
      and for a longer period of time than NS-NSAIDs, and that their use is less
      frequently associated with GPAs.

PMID- 17536890
TI  - Effectiveness and Safety of Amlodipine in Newly Diagnosed Hypertensive Patients
      and in Previously Diagnosed Hypertensive Patients not Controlled with their Usual
      Treatment (NOTA Study).
AB  - OBJECTIVE: To evaluate the effectiveness and safety of amlodipine in two cohorts
      of hypertensive patients, one newly diagnosed and the other previously diagnosed
      but not controlled with drug therapy, and to assess the risk factors for the
      entire sample at the outset of the study. PATIENTS AND DESIGN: We designed a
      postmarketing, multicentre, open-label, prospective, observational surveillance
      study with a 6-month follow-up, which included hypertensive patients (systolic
      blood pressure [SBP] >/=140mm Hg and/or diastolic blood pressure [DBP] >/=90mm
      Hg) who attended specialised units and had either newly diagnosed or previously
      diagnosed pharmacologically uncontrolled arterial hypertension. RESULTS: Of the
      total of 1797 patients eligible for evaluation, 760 (42.3%) were newly and 1037
      (57.7%) were previously diagnosed. Of these, 22.9% were classified as being in
      the high-risk and 43.2% in the very high-risk groups at the outset of the study
      (WHO-ISH [International Society of Hypertension]). On conclusion of the 6-month
      follow-up, 54.3% of newly diagnosed and 44.4% of previously treated patients had
      attained the BP therapy targets defined as SBP <140mm Hg and DBP <90mm Hg,
      representing a statistically significant difference (p < 0.0001). A total of 8%
      of patients experienced some adverse event during the course of the study, with
      this percentage being somewhat higher in the previously treated than in the newly
      diagnosed group (10.8% vs 5.1%, p < 0.0001). Only 0.3% experienced some severe
      adverse event, although in no case was this linked to the drug under evaluation.
      CONCLUSIONS: We conclude that amlodipine has shown itself to be an effective and
      safe drug for the control of hypertension, whether isolated or associated with
      other cardiovascular risk factors, both in patients without a previous diagnosis
      of arterial hypertension and in those previously diagnosed although not
      controlled under a prior treatment regimen.

PMID- 17536891
TI  - Bioequivalence of rebamipide granules and tablets in healthy adult male
      volunteers.
AB  - OBJECTIVE: Rebamipide tablets, which are used in the treatment of patients with
      gastric ulcers or gastritis, can be difficult to administer in subjects with
      reduced swallowing ability or impaired swallowing. The granule formulation may be
      more easily administered in these patients. The bioequivalence between rebamipide
      granules (20%/0.5g) and tablets (100mg) was determined in healthy male adult
      volunteers, in accordance with the Partially Revised Guidelines for
      Bioequivalence Studies of Generic Products. STUDY DESIGN: In a randomised,
      nonblind, crossover design, 28 individuals were allocated into two groups of 14
      to receive either rebamipide granules or rebamipide tablets. Each individual,
      under fasting conditions, was administered a single oral dose of rebamipide 100mg
      followed by a 7-day washout period. Individuals then received a single oral dose
      of the other rebamipide formulation. Blood samples were collected at 0.5, 1, 1.5,
      2, 3, 4, 6, 8, 12 and 24 hours. Plasma rebamipide concentrations were measured by
      validated high-performance liquid chromatography with tandem mass spectrometry.
      RESULTS: The plasma concentration-time profiles and pharmacokinetic parameters of
      rebamipide after administration of the granule formulation were similar to those
      of the tablet in 27 healthy male volunteers. Following administration of the
      granule formulation, the area under the plasma concentration-time curve from time
      0-24 hours (AUC(24h)) was 912.82 mug/L . h, the maximum plasma concentration
      (C(max)) was 241.82 mug/L, time to maximum plasma concentration (t(max)) was 2.5
      hours, and plasma elimination half-life (t((1/2))) was 1.97 hours. Corresponding
      values for the tablet formulation were 873.55 microg/L . h, 216.19 mug/L, 2.4
      hours, and 1.94 hours. The difference in mean log values was 1.01 for AUC(24h)
      and 1.09 for C(max) after granule and tablet administration. The 90% confidence
      interval of this difference in mean log value was 0.93-1.10 for AUC(24h), and
      0.97-1.21 for C(max). This satisfies the criteria for bioequivalence in the
      guidelines [within log (0.8) to log (1.25)]. CONCLUSIONS: Rebamipide granules
      (20%/0.5g) and tablet (100mg) were bioequivalent. Rebamipide granules may
      therefore be a more practical treatment option in patients with gastric ulcers or
      gastritis who have difficulty swallowing tablets.

PMID- 17536892
TI  - Efficacy of low-dose tamsulosin in chinese patients with symptomatic benign
      prostatic hyperplasia.
AB  - OBJECTIVE: To determine the efficacy and tolerability of low-dose tamsulosin 0.2
      mg/day in Chinese patients with symptomatic benign prostatic hyperplasia (BPH).
      METHODS: A total of 505 patients were enrolled in a 6-week nonblind, multicentre
      study, and 499 patients were followed for the entire 6-week treatment period.
      After a 2-week washout period, patients with confirmed symptomatic BPH were
      treated with tamsulosin 0.2mg daily. International Prostate Symptom Score (I
      PSS), quality-of-life (QOL) index, maximum urinary flow rate (Q(max)) and average
      urinary flow rate (Q(ave)) were the efficacy parameters. Adverse events and
      variations in blood pressure and heart rate were also monitored. RESULTS: Total I
      PSS and QOL index scores were improved from baseline with an average score
      reduction of 7.50 and 1.40, respectively (p < 0.01). Mean Q(max) and Q(ave) were
      increased by an average of 4.33 mL/sec (p < 0.01) and 2.04 mL/sec, respectively
      (p < 0.01). A subgroup analysis showed that total I-PSS, QOL index and Q(max)
      were significantly improved irrespective of baseline I-PSS, age, duration of BPH,
      comorbid conditions, or the use of concomitant antihypertensive agents. A
      positive correlation was noted between improvement in total I-PSS and QOL index
      (r = 0.70). Relative to baseline, systolic and diastolic blood pressure decreased
      by a mean of 3.35mm Hg and 2.74mm Hg, respectively (p < 0.01). A total of 28
      treatment-related adverse reactions were reported in 24 patients (4.75%), the
      majority of which were mild dizziness and headache. CONCLUSIONS: Low-dose
      tamsulosin 0.2 mg/day has a favourable efficacy and tolerability profile in
      Chinese patients with symptomatic BPH irrespective of the baseline
      characteristics of these patients. No serious, unexpected adverse effects were
      identified.

PMID- 17536893
TI  - Effects of D-003 on the Lipid Profile of Patients with Type II
      Hypercholesterolaemia : A Phase II Clinical Study.
AB  - BACKGROUND: D-003 is a cholesterol-lowering agent that is isolated and purified
      from sugarcane wax and has concomitant antiplatelet effects. OBJECTIVE: To
      evaluate lipid profile responses to different doses of D-003 in patients with
      type II hypercholesterolaemia. STUDY DESIGN: An 8-week, double-blind, placebo
      controlled, parallel-group clinical study. METHODS: After concluding a 5-week
      diet-only baseline period, 55 patients were randomly allocated to receive either
      placebo or D-003 at 5, 10, 20 or 40mg once daily with their evening meal for 8
      weeks. An interim check-up was performed at week 4. The primary efficacy variable
      was the reduction of serum low-density lipoprotein-cholesterol (LDL-C) from
      baseline compared with placebo. Drug safety and tolerability were assessed on the
      basis of changes in physical, haematological and blood biochemical indicators and
      on questioning about adverse experiences (AEs). RESULTS: After 8 weeks of
      therapy, D-003 significantly lowered (p < 0.0001 vs baseline and placebo) serum
      LDL-C in a dose-related manner, with reductions of 20.5-26.1% from the lowest to
      the highest dose investigated. At study completion, 43 of 44 (97.7%) randomised
      patients treated with D-003 reached LDL-C reductions >15% compared with baseline,
      while 30 of 44 patients (68.2%) reached LDL-C targets according to their
      individual global coronary risk status. Decreases in total cholesterol (TC) and
      the ratios of TC/high-density lipoprotein-cholesterol (HDL-C) and LDL-C/HDL-C
      were also significant (p < 0.0001) and dose related. Changes in LDL-C, TC and
      both ratios were significant from the interim check-up. D-003 significantly
      increased HDL-C values (11.7-16.7%), but the increase was not dose related. No
      significant changes in lipid profile variables were observed with placebo. D-003
      was well tolerated. The treatment did not affect any physical, haematological or
      blood safety indicators. All included patients completed the study. Four patients
      reported mild AEs during the study: headache (one patient treated with placebo
      and one treated with D-003 20 mg/day), insomnia (one patient treated with D-003 5
      mg/day) and polyuria (one patient treated with D-003 40 mg/day). CONCLUSIONS: D
      003 was effective in dose dependently reducing LDL-C in patients with type II
      hypercholesterolaemia, as documented by average percentage reductions and the
      percentage of patients achieving decreases >15% from baseline and LDL-C goals.
      The treatment was well tolerated by patients and did not affect any safety
      indicator. Further studies corroborating these results and exploring the effect
      of lower doses of D-003 and a longer treatment duration must be carried out,
      however, before definitive conclusions can be reached. These results encourage
      continuing clinical investigation on this drug.

PMID- 17536894
TI  - A Possible Association between Oral Aminophylline Treatment during Pregnancy and
      Skeletal Congenital Abnormalities.
AB  - OBJECTIVE: To study the human teratogenic potential of oral aminophylline
      treatment during pregnancy. DESIGN AND SETTING: The analysis of each case and its
      matched controls, as well as comparison of population or patient controls and
      cases with 25 groups of congenital abnormalities in the population-based data set
      of the large Hungarian Case-Control Surveillance of Congenital Abnormalities,
      1980-1996. STUDY PARTICIPANTS: 38 151 pregnant women who had newborn infants
      without any congenital abnormalities (population control group), 22 843 pregnant
      women who had newborn infants or fetuses with congenital abnormalities, and 834
      patient controls with Down's syndrome. MAIN OUTCOME MEASURES: Prevalence of
      aminophylline use in cases with the 25 congenital abnormality groups compared
      with population control and patient control groups. RESULTS: The prevalence of
      oral aminophylline treatment during pregnancy was similar in the case group (1374
      pregnant women; 6.0%) and the population control group (2284 pregnant women;
      6.0%) [crude prevalence odds ratio (POR) 1.0, 95% confidence interval (CI) 0.9
      1.1], while it was higher in the patient control group (55 pregnant women; 6.6%).
      Comparisons of total population or patient control groups and cases with the 25
      different congenital abnormality groups, as well as analysis of cases and their
      matched controls, indicated an association between aminophylline use and
      congenital abnormalities of the musculoskeletal system (crude POR 5.0, 95% CI 1.4
      18.4, adjusted POR 4.7, 95% CI 1.3-17.2 for aminophylline treatment during the
      second through third months of gestation; crude POR 1.5, 95% CI 1.0-2.2, adjusted
      POR 1.5, 95% CI 0.9-2.2 for aminophylline treatment during the entire pregnancy),
      particularly pectus excavatum/carinatum (3.5 times excess). There was a possible
      association between aminophylline and clubfoot and posterior cleft palate. These
      findings may be connected with recall bias, although this bias was restricted by
      the evaluation of maternal drug use only during the critical period of the above
      congenital abnormalities and by evaluating medically recorded aminophylline
      treatment, as well as by the use of patient controls. CONCLUSION: Our findings
      and previous animal investigations can only be regarded as a signal for the
      possible association between oral treatment with aminophylline during pregnancy
      and some congenital abnormalities of the skeletal system.

PMID- 17536895
TI  - Antineutrophil cytoplasmic antibody-positive vasculitis associated with
      propylthiouracil therapy.

PMID- 17536896
TI  - A CT-based high-order finite element analysis of the human proximal femur
      compared to in-vitro experiments.
AB  - The prediction of patient-specific proximal femur mechanical response to various
      load conditions is of major clinical importance in orthopaedics. This paper
      presents a novel, empirically validated high-order finite element method (FEM)
      for simulating the bone response to loads. A model of the bone geometry was
      constructed from a quantitative computerized tomography (QCT) scan using smooth
      surfaces for both the cortical and trabecular regions. Inhomogeneous isotropic
      elastic properties were assigned to the finite element model using distinct
      continuous spatial fields for each region. The Young's modulus was represented as
      a continuous function computed by a least mean squares method. p-FEMs were used
      to bound the simulation numerical error and to quantify the modeling assumptions.
      We validated the FE results with in-vitro experiments on a fresh-frozen femur
      loaded by a quasi-static force of up to 1500 N at four different angles. We
      measured the vertical displacement and strains at various locations and
      investigated the sensitivity of the simulation. Good agreement was found for the
      displacements, and a fair agreement found in the measured strain in some of the
      locations. The presented study is a first step toward a reliable p-FEM simulation
      of human femurs based on QCT data for clinical computer aided decision making.

PMID- 17536897
TI  - The effect of cross-sectional stem shape on the torsional stability of cemented
      implant components.
AB  - Stability of a cemented implant, once the stem-cement interface has debonded, is
      reliant upon stem geometry and surface finish. There are relatively few studies
      addressing the effect of cross-sectional stem shape on cemented implant fixation.
      The purpose of this investigation was to compare the torsional stability of five
      different stem cross-sectional shapes-circular, oval, triangular, rectangular
      with rounded edges, and rectangular with sharp edges-under monotonically
      increasing and cyclic loading conditions. Seven samples of each stem geometry
      were tested. Stems were potted in bone cement and loaded to 5 deg of rotation.
      For monotonic loading, torque was applied at a constant rate of 2.5 deg/min. For
      cyclic loading, a sine wave torque pattern was applied, with a maximum magnitude
      that began at 4.5 Nm for 1500 cycles and then increased by 2.25 Nm every 1500
      cycles until 5 deg of rotation. The rectangular stem with the sharp edges always
      provided the greatest resistance to torque, followed by the rectangular with
      rounded edges, triangular, oval, and circular. These results, including the
      effects of sharp corners, may differ for modes of loading other than torsion.
      These experimental results support the findings of earlier finite element models,
      indicating stem shape has a significant effect on resistance to torsional
      loading.

PMID- 17536898
TI  - Constitutive material modeling of cell: a micromechanics approach.
AB  - The variations in mechanical properties of cells obtained from experimental and
      theoretical studies can be overcome only through the development of a sound
      mathematical framework correlating the derived mechanical property with the
      cellular structure. Such a formulation accounting for the inhomogeneity of the
      cytoplasm due to stress fibers and actin cortex is developed in this work. The
      proposed model is developed using the Mori-Tanaka method of homogenization by
      treating the cell as a fiber-reinforced composite medium satisfying the continuum
      hypothesis. The validation of the constitutive model using finite element
      analysis on atomic force microscopy (AFM) and magnetic twisting cytometry (MTC)
      has been carried out and is found to yield good correlation with reported
      experimental results. It is observed from the study that as the volume fraction
      of the stress fiber increases, the stiffness of the cell increases and it alters
      the force displacement behavior for the AFM and MTC experiments. Through this
      model, we have also been able to find the stress fiber as a likely cause of the
      differences in the derived mechanical property from the AFM and MTC experiments.
      The correlation of the mechanical behavior of the cell with the cell composition,
      as obtained through this study, is an important observation in cell mechanics.

PMID- 17536899
TI  - Change in properties of the glycocalyx affects the shear rate and stress
      distribution on endothelial cells.
AB  - The endothelial glycocalyx mediates interactions between the blood flow and the
      endothelium. This study aims to evaluate, quantitatively, effects of structural
      change of the glycocalyx on stress distribution and shear rate on endothelial
      cells. In the study, the endothelial glycocalyx is modeled as a surface layer of
      fiber matrix and when exposed to laminar shear flow, the matrix deforms. Fluid
      velocity and stress distribution inside the matrix and on cell membranes are
      studied based on a binary mixture theory. Parameters, such as the height and
      porosity of the matrix and the drag coefficient between fluid and matrix fibrils,
      are based on available data and estimation from experiments. Simple theoretical
      solutions are achieved for fluid velocity and stress distribution in the surface
      matrix. Degradation of the matrix, e.g., by enzyme digestion, is represented by
      reductions in the volume fraction of fibrils, height, and drag coefficient. From
      a force balance, total stress on endothelial surface remains constant regardless
      of structural alteration of the glycocalyx. However, the stress that is
      transmitted to endothelial cells by direct "pulling" of fiber branches of the
      glycocalyx is reduced significantly. Fluid shear rate at the cell membrane, on
      the other hand, increases. The study gives quantitative insight into the effect
      of the structural change of the glycocalyx on the shear rate and pulling stress
      on the endothelium. Results can be used to interpret experiments on effects of
      the glycocalyx in shear induced endothelial responses.

PMID- 17536900
TI  - Numerical assessment of thermal response associated with in vivo skin
      electroporation: the importance of the composite skin model.
AB  - Electroporation is an approach used to enhance transdermal transport of large
      molecules in which the skin is exposed to a series of electric pulses. The
      structure of the transport inhibiting outer layer, the stratum corneum, is
      temporarily destabilized due to the development of microscopic pores.
      Consequently agents that are ordinarily unable to pass into the skin are able to
      pass through this outer barrier. Of possible concern when exposing biological
      tissue to an electric field is thermal tissue damage associated with Joule
      heating. This paper shows the importance of using a composite model in
      calculating the electrical and thermal effects associated with skin
      electroporation. A three-dimensional transient finite-volume model of in vivo
      skin electroporation is developed to emphasize the importance of representing the
      skin's composite layers and to illustrate the underlying relationships between
      the physical parameters of the composite makeup of the skin and resulting thermal
      damage potential.

PMID- 17536901
TI  - Transport characteristics of expiratory droplets and droplet nuclei in indoor
      environments with different ventilation airflow patterns.
AB  - Expiratory droplets and droplet nuclei can be pathogen carriers for airborne
      diseases. Their transport characteristics were studied in detail in two idealized
      floor-supply-type ventilation flow patterns: Unidirectional-upward and single
      side-floor, using a multiphase numerical model. The model was validated by
      running interferometric Mie imaging experiments using test droplets with
      nonvolatile content, which formed droplet nuclei, ultimately, in a class-100
      clean-room chamber. By comparing the droplet dispersion and removal
      characteristics with data of two other ceiling-supply ventilation systems
      collected from a previous work, deviations from the perfectly mixed ventilation
      condition were found to exist in various cases to different extent. The
      unidirectional-upward system was found to be more efficient in removing the
      smallest droplet nuclei (formed from 1.5 mum droplets) by air extraction, but it
      became less effective for larger droplets and droplet nuclei. Instead, the single
      side-floor system was shown to be more favorable in removing these large droplets
      and droplet nuclei. In the single-side-floor system, the lateral overall
      dispersion coefficients for the small droplets and nuclei (initial size </=45
      mum) were about an order of magnitude higher than those in the unidirectional
      upward system. It indicated that bulk lateral airflow transport in the single
      side-floor system was much stronger than the lateral dispersion mechanism induced
      mainly by air turbulence in the unidirectional-upward system. The time required
      for the droplets and droplet nuclei to be transported to the exhaust vent or
      deposition surfaces for removal varied with different ventilation flow patterns.
      Possible underestimation of exposure level existed if the perfectly mixed
      condition was assumed. For example, the weak lateral dispersion in the
      unidirectional ventilation systems made expiratory droplets and droplet nuclei
      stay at close distance to the source leading to highly nonuniform spatial
      distributions. The distance between the source and susceptible patients became an
      additional concern in exposure analysis. Relative significance of the air
      extraction removal mechanism was studied. This can have impact to the performance
      evaluation of filtration and disinfection systems installed in the indoor
      environment. These findings revealed the need for further development in a risk
      assessment model incorporating the effect of different ventilation systems on
      distributing expiratory droplets and droplet nuclei nonuniformly in various
      indoor spaces, such as buildings, aircraft cabins, trains, etc.

PMID- 17536902
TI  - Radio-frequency ablation in a realistic reconstructed hepatic tissue.
AB  - This study uses a reconstructed vascular geometry to evaluate the thermal
      response of tissue during a three-dimensional radiofrequency (rf) tumor ablation.
      MRI images of a sectioned liver tissue containing arterial vessels are processed
      and converted into a finite-element mesh. A rf heat source in the form of a
      spherically symmetric Gaussian distribution, fit from a previously computed
      profile, is employed. Convective cooling within large blood vessels is treated
      using direct physical modeling of the heat and momentum transfer within the
      vessel. Calculations of temperature rise and thermal dose are performed for
      transient rf procedures in cases where the tumor is located at three different
      locations near the bifurcation point of a reconstructed artery. Results
      demonstrate a significant dependence of tissue temperature profile on the
      reconstructed vasculature and the tumor location. Heat convection through the
      arteries reduced the steady-state temperature rise, relative to the no-flow case,
      by up to 70% in the targeted volume. Blood flow also reduced the thermal dose
      value, which quantifies the extent of cell damage, from approximately 3600 min,
      for the no-flow condition, to 10 min for basal flow (13.8 cms). Reduction of
      thermal dose below the threshold value of 240 min indicates ablation procedures
      that may inadequately elevate the temperature in some regions, thereby permitting
      possible tumor recursion. These variations are caused by vasculature tortuosity
      that are patient specific and can be captured only by the reconstruction of the
      realistic geometry.

PMID- 17536903
TI  - Numerical simulation on mass transport in a microchannel bioreactor for co
      culture applications.
AB  - Microchannel bioreactors have applications for manipulating and investigating the
      fluid microenvironment on cell growth and functions in either single culture or
      co-culture. This study considers two different types of cells distributed
      randomly as a co-culture at the base of a microchannel bioreactor: absorption
      cells, which only consume species based on the Michaelis-Menten process, and
      release cells, which secrete species, assuming zeroth order reaction, to support
      the absorption cells. The species concentrations at the co-culture cell base are
      computed from a three-dimensional numerical flow-model incorporating mass
      transport. Combined dimensionless parameters are proposed for the co-culture
      system, developed from a simplified analysis under the condition of decreasing
      axial-concentration. The numerical results of species concentration at the co
      culture cell-base are approximately correlated by the combined parameters under
      the condition of positive flux-parameter. Based on the correlated results, the
      critical value of the inlet concentration is determined, which depends on the
      effective microchannel length. For the flow to develop to the critical inlet
      concentration, an upstream length consisting only of release cells is needed;
      this upstream length is determined from an analytical solution. The generalized
      results may find applications in analyzing the mass transport requirements in a
      co-culture microchannel bioreactor.

PMID- 17536904
TI  - Multiphysics simulation of blood flow and LDL transport in a porohyperelastic
      arterial wall model.
AB  - Atherosclerosis localizes at a bend andor bifurcation of an artery, and low
      density lipoproteins (LDL) accumulate in the intima. Hemodynamic factors are
      known to affect this localization and LDL accumulation, but the details of the
      process remain unknown. It is thought that the LDL concentration will be affected
      by the filtration flow, and that the velocity of this flow will be affected by
      deformation of the arterial wall. Thus, a coupled model of a blood flow and a
      deformable arterial wall with filtration flow would be invaluable for simulation
      of the flow field and concentration field in sequence. However, this type of
      highly coupled interaction analysis has not yet been attempted. Therefore, we
      performed a coupled analysis of an artery with multiple bends in sequence. First,
      based on the theory of porous media, we modeled a deformable arterial wall using
      a porohyperelastic model (PHEM) that was able to express both the filtration flow
      and the viscoelastic behavior of the living tissue, and simulated a blood flow
      field in the arterial lumen, a filtration flow field and a displacement field in
      the arterial wall using a fluid-structure interaction (FSI) program code by the
      finite element method (FEM). Next, based on the obtained results, we further
      simulated LDL transport using a mass transfer analysis code by the FEM. We
      analyzed the PHEM in comparison with a rigid model. For the blood flow,
      stagnation was observed downward of the bends. The direction of the filtration
      flow was only from the lumen to the wall for the rigid model, while filtration
      flows from both the wall to the lumen and the lumen to the wall were observed for
      the PHEM. The LDL concentration was high at the lumenwall interface for both the
      PHEM and rigid model, and reached its maximum value at the stagnation area. For
      the PHEM, the maximum LDL concentration in the wall in the radial direction was
      observed at the position of 3% wall thickness from the lumenwall interface, while
      for the rigid model, it was observed just at the lumenwall interface. In
      addition, the peak LDL accumulation area of the PHEM moved about according to the
      pulsatile flow. These results demonstrate that the blood flow, arterial wall
      deformation, and filtration flow all affect the LDL concentration, and that LDL
      accumulation is due to stagnation and the presence of filtration flow. Thus, FSI
      analysis is indispensable.

PMID- 17536905
TI  - Effect of ACL deficiency on MCL strains and joint kinematics.
AB  - The knee joint is partially stabilized by the interaction of multiple ligament
      structures. This study tested the interdependent functions of the anterior
      cruciate ligament (ACL) and the medial collateral ligament (MCL) by evaluating
      the effects of ACL deficiency on local MCL strain while simultaneously measuring
      joint kinematics under specific loading scenarios. A structural testing machine
      applied anterior translation and valgus rotation (limits 100 N and 10 N m,
      respectively) to the tibia of ten human cadaveric knees with the ACL intact or
      severed. A three-dimensional motion analysis system measured joint kinematics and
      MCL tissue strain in 18 regions of the superficial MCL. ACL deficiency
      significantly increased MCL strains by 1.8% (p<0.05) during anterior translation,
      bringing ligament fibers to strain levels characteristic of microtrauma. In
      contrast, ACL transection had no effect on MCL strains during valgus rotation
      (increase of only 0.1%). Therefore, isolated valgus rotation in the ACL-deficient
      knee was nondetrimental to the MCL. The ACL was also found to promote internal
      tibial rotation during anterior translation, which in turn decreased strains near
      the femoral insertion of the MCL. These data advance the basic structure-function
      understanding of the MCL, and may benefit the treatment of ACL injuries by
      improving the knowledge of ACL function and clarifying motions that are
      potentially harmful to secondary stabilizers.

PMID- 17536906
TI  - Determining fall direction and impact location for various disturbances and gait
      speeds using the articulated total body model.
AB  - Because fall experiments with volunteers can be both challenging and risky,
      especially with older volunteers, we wished to develop computer simulations of
      falls to provide a theoretical framework for understanding and extending
      experimental results. To perform a preliminary validation of the articulated
      total body (ATB) model for passive falls, we compared the model predictions of
      fall direction, impact location, and impact velocity as a function of disturbance
      type (faint, slip, step down, trip) and gait speed (fast, normal, slow) to
      experimental results with young adult volunteers. The three-dimensional ATB model
      had 17 segments and 16 joints. Its physical characteristics, environment
      definitions, contact functions, and initial conditions were representative of our
      experiment. For each combination of disturbance and gait speed, the ATB model was
      left to fall passively under gravity once disturbed, i.e., no joint torques were
      applied, until impact with the floor occurred. Finally, we also determined the
      sensitivity of the model predictions to changes in the model's parameters. Our
      model predictions of fall angles and impact angles were qualitatively in
      agreement with those observed experimentally for ten and seven of the 12 original
      simulations, respectively. Quantitatively, the model predictions of fall angles,
      impact angles, and impact velocities were within one experimental standard
      deviation for seven, three, and nine of the 12 original simulations,
      respectively, and within two experimental standard deviations for ten, nine, and
      11 of the 12 original simulations, respectively. Finally, the fall angle and
      impact angle region did not change for 92% and 95% of the 74 input variation
      simulations, respectively, and the impact velocities were within the experimental
      standard deviations for 78% of the 74 input variation simulations. Based on our
      simulations and a sensitivity analysis, we conclude that our preliminary
      validation of the ATB model for passive falls was successful. In fact, these ATB
      model simulations represent a significant step forward in fall simulations. We
      believe that with additional work, the ATB model could be used to accurately
      simulate a variety of human falls and may be useful in further understanding the
      etiology and mechanisms of fall injuries such as hip fractures.

PMID- 17536907
TI  - Long durations of immobilization in the rat result in enhanced mechanical
      properties of the healing supraspinatus tendon insertion site.
AB  - Rotator cuff tears frequently occur and can lead to pain and decreased shoulder
      function. Repair of the torn tendon back to bone is often successful in relieving
      pain, but failure of the repair commonly occurs. Post-operative activity level is
      an important treatment component that has received minimal attention for the
      shoulder, but may have the potential to enhance tendon to bone healing. The
      objective of this study was to investigate the effect of short and long durations
      of various activity levels on the healing supraspinatus tendon to bone insertion
      site. Rotator cuff tears were surgically created in Sprague-Dawley rats by
      detaching the supraspinatus tendon from its insertion on the humerus and these
      tears were immediately repaired back to the insertion site. The post-operative
      activity level was controlled through shoulder immobilization (IM), cage activity
      (CA), or moderate exercise (EX) for durations of 4 or 16 weeks. The healing
      tissue was evaluated utilizing biomechanical testing and a quantitative polarized
      light microscopy method. We found that activity level had no effect on the
      elastic properties (stiffness, modulus) of the insertion site at four weeks post
      injury and repair, and a decreased activity level had a positive effect on these
      properties at 16 weeks (IM>CA=EX). Furthermore, a decreased activity level had
      the greatest positive effect on these properties over time (IM>CA=EX). The
      angular deviation of the collagen, a measure of disorganization, was decreased
      with a decrease in activity level at 4 weeks (IM<CA=EX), but was similar between
      groups at 16 weeks (IM=CA=EX). It appears from this study that decreasing the
      activity level by immobilizing the shoulder improves tendon to bone healing,
      which progresses by first increasing the organization of the collagen and then
      increasing the mechanical properties. Future studies in this area will
      investigate the effect of passive motion and remobilization on both tendon to
      bone healing and shoulder function.

PMID- 17536908
TI  - Equivalence between short-time biphasic and incompressible elastic material
      responses.
AB  - Porous-permeable tissues have often been modeled using porous media theories such
      as the biphasic theory. This study examines the equivalence of the short-time
      biphasic and incompressible elastic responses for arbitrary deformations and
      constitutive relations from first principles. This equivalence is illustrated in
      problems of unconfined compression of a disk, and of articular contact under
      finite deformation, using two different constitutive relations for the solid
      matrix of cartilage, one of which accounts for the large disparity observed
      between the tensile and compressive moduli in this tissue. Demonstrating this
      equivalence under general conditions provides a rationale for using available
      finite element codes for incompressible elastic materials as a practical
      substitute for biphasic analyses, so long as only the short-time biphasic
      response is sought. In practice, an incompressible elastic analysis is
      representative of a biphasic analysis over the short-term response
      deltat<<Delta(2) / //parallelC(4)//K//, where Delta is a characteristic
      dimension, C(4) is the elasticity tensor, and K is the hydraulic permeability
      tensor of the solid matrix. Certain notes of caution are provided with regard to
      implementation issues, particularly when finite element formulations of
      incompressible elasticity employ an uncoupled strain energy function consisting
      of additive deviatoric and volumetric components.

PMID- 17536909
TI  - Extraction of mechanical properties of articular cartilage from osmotic swelling
      behavior monitored using high frequency ultrasound.
AB  - Articular cartilage is a biological weight-bearing tissue covering the bony ends
      of articulating joints. Negatively charged proteoglycan (PG) in articular
      cartilage is one of the main factors that govern its compressive mechanical
      behavior and swelling phenomenon. PG is nonuniformly distributed throughout the
      depth direction, and its amount or distribution may change in the degenerated
      articular cartilage such as osteoarthritis. In this paper, we used a 50 MHz
      ultrasound system to study the depth-dependent strain of articular cartilage
      under the osmotic loading induced by the decrease of the bathing saline
      concentration. The swelling-induced strains under the osmotic loading were used
      to determine the layered material properties of articular cartilage based on a
      triphasic model of the free-swelling. Fourteen cylindrical cartilage-bone samples
      prepared from fresh normal bovine patellae were tested in situ in this study. A
      layered triphasic model was proposed to describe the depth distribution of the
      swelling strain for the cartilage and to determine its aggregate modulus H(a) at
      two different layers, within which H(a) was assumed to be linearly dependent on
      the depth. The results showed that H(a) was 3.0+/-3.2, 7.0+/-7.4, 24.5+/-11.1 MPa
      at the cartilage surface, layer interface, and deep region, respectively. They
      are significantly different (p<0.01). The layer interface located at 70%+/-20% of
      the overall thickness from the uncalcified-calcified cartilage interface.
      Parametric analysis demonstrated that the depth-dependent distribution of the
      water fraction had a significant effect on the modeling results but not the fixed
      charge density. This study showed that high-frequency ultrasound measurement
      together with triphasic modeling is practical for quantifying the layered
      mechanical properties of articular cartilage nondestructively and has the
      potential for providing useful information for the detection of the early signs
      of osteoarthritis.

PMID- 17536910
TI  - Effects of tension-compression nonlinearity on solute transport in charged
      hydrated fibrous tissues under dynamic unconfined compression.
AB  - Cartilage is a charged hydrated fibrous tissue exhibiting a high degree of
      tension-compression nonlinearity (i.e., tissue anisotropy). The effect of tension
      compression nonlinearity on solute transport has not been investigated in
      cartilaginous tissue under dynamic loading conditions. In this study, a new model
      was developed based on the mechano-electrochemical mixture model [Yao and Gu,
      2007, J. Biomech. Model Mechanobiol., 6, pp. 63-72, Lai et al., 1991, J. Biomech.
      Eng., 113, pp. 245-258], and conewise linear elasticity model [Soltz and
      Ateshian, 2000, J. Biomech. Eng., 122, pp. 576-586; Curnier et al., 1995, J.
      Elasticity, 37, pp. 1-38]. The solute desorption in cartilage under unconfined
      dynamic compression was investigated numerically using this new model. Analyses
      and results demonstrated that a high degree of tissue tension-compression
      nonlinearity could enhance the transport of large solutes considerably in the
      cartilage sample under dynamic unconfined compression, whereas it had little
      effect on the transport of small solutes (at 5% dynamic strain level). The
      loading-induced convection is an important mechanism for enhancing the transport
      of large solutes in the cartilage sample with tension-compression nonlinearity.
      The dynamic compression also promoted diffusion of large solutes in both tissues
      with and without tension-compression nonlinearity. These findings provide a new
      insight into the mechanisms of solute transport in hydrated, fibrous soft
      tissues.

PMID- 17536911
TI  - Robust strategies for automated AFM force curve analysis--I. Non-adhesive
      indentation of soft, inhomogeneous materials.
AB  - The atomic force microscope (AFM) has found wide applicability as a
      nanoindentation tool to measure local elastic properties of soft materials. An
      automated approach to the processing of AFM indentation data, namely, the
      extraction of Young's modulus, is essential to realizing the high-throughput
      potential of the instrument as an elasticity probe for typical soft materials
      that exhibit inhomogeneity at microscopic scales. This paper focuses on Hertzian
      analysis techniques, which are applicable to linear elastic indentation. We
      compiled a series of synergistic strategies into an algorithm that overcomes many
      of the complications that have previously impeded efforts to automate the fitting
      of contact mechanics models to indentation data. AFM raster data sets containing
      up to 1024 individual force-displacement curves and macroscopic compression data
      were obtained from testing polyvinyl alcohol gels of known composition. Local
      elastic properties of tissue-engineered cartilage were also measured by the AFM.
      All AFM data sets were processed using customized software based on the
      algorithm, and the extracted values of Young's modulus were compared to those
      obtained by macroscopic testing. Accuracy of the technique was verified by the
      good agreement between values of Young's modulus obtained by AFM and by direct
      compression of the synthetic gels. Validation of robustness was achieved by
      successfully fitting the vastly different types of force curves generated from
      the indentation of tissue-engineered cartilage. For AFM indentation data that are
      amenable to Hertzian analysis, the method presented here minimizes subjectivity
      in preprocessing and allows for improved consistency and minimized user
      intervention. Automated, large-scale analysis of indentation data holds
      tremendous potential in bioengineering applications, such as high-resolution
      elasticity mapping of natural and artificial tissues.

PMID- 17536912
TI  - Computational model for the transition from peristaltic to pulsatile flow in the
      embryonic heart tube.
AB  - Early in development, the heart is a single muscle-wrapped tube without formed
      valves. Yet survival of the embryo depends on the ability of this tube to pump
      blood at steadily increasing rates and pressures. Developmental biologists
      historically have speculated that the heart tube pumps via a peristaltic
      mechanism, with a wave of contraction propagating from the inflow to the outflow
      end. Physiological measurements, however, have shown that the flow becomes
      pulsatile in character quite early in development, before the valves form. Here,
      we use a computational model for flow though the embryonic heart to explore the
      pumping mechanism. Results from the model show that endocardial cushions, which
      are valve primordia arising near the ends of the tube, induce a transition from
      peristaltic to pulsatile flow. Comparison of numerical results with published
      experimental data shows reasonably good agreement for various pressure and flow
      parameters. This study illustrates the interrelationship between form and
      function in the early embryonic heart.

PMID- 17536913
TI  - The nonlinear material properties of liver tissue determined from no-slip
      uniaxial compression experiments.
AB  - The mechanical response of soft tissue is commonly characterized from unconfined
      uniaxial compression experiments on cylindrical samples. However, friction
      between the sample and the compression platens is inevitable and hard to
      quantify. One alternative is to adhere the sample to the platens, which leads to
      a known no-slip boundary condition, but the resulting nonuniform state of stress
      in the sample makes it difficult to determine its material parameters. This paper
      presents an approach to extract the nonlinear material properties of soft tissue
      (such as liver) directly from no-slip experiments using a set of computationally
      determined correction factors. We assume that liver tissue is an isotropic,
      incompressible hyperelastic material characterized by the exponential form of
      strain energy function. The proposed approach is applied to data from experiments
      on bovine liver tissue. Results show that the apparent material properties, i.e.,
      those determined from no-slip experiments ignoring the no-slip conditions, can
      differ from the true material properties by as much as 50% for the exponential
      material model. The proposed correction approach allows one to determine the true
      material parameters directly from no-slip experiments and can be easily extended
      to other forms of hyperelastic material models.

PMID- 17536914
TI  - A Lagrange multiplier mixed finite element formulation for three-dimensional
      contact of biphasic tissues.
AB  - A three-dimensional (3D) contact finite element formulation has been developed
      for biological soft tissue-to-tissue contact analysis. The linear biphasic theory
      of Mow, Holmes, and Lai (1984, J. Biomech., 17(5), pp. 377-394) based on
      continuum mixture theory, is adopted to describe the hydrated soft tissue as a
      continuum of solid and fluid phases. Four contact continuity conditions derived
      for biphasic mixtures by Hou et al. (1989, ASME J. Biomech. Eng., 111(1), pp. 78
      87) are introduced on the assumed contact surface, and a weighted residual method
      has been used to derive a mixed velocity-pressure finite element contact
      formulation. The Lagrange multiplier method is used to enforce two of the four
      contact continuity conditions, while the other two conditions are introduced
      directly into the weighted residual statement. Alternate formulations are
      possible, which differ in the choice of continuity conditions that are enforced
      with Lagrange multipliers. Primary attention is focused on a formulation that
      enforces the normal solid traction and relative fluid flow continuity conditions
      on the contact surface using Lagrange multipliers. An alternate approach, in
      which the multipliers enforce normal solid traction and pressure continuity
      conditions, is also discussed. The contact nonlinearity is treated with an
      iterative algorithm, where the assumed area is either extended or reduced based
      on the validity of the solution relative to contact conditions. The resulting
      first-order system of equations is solved in time using the generalized finite
      difference scheme. The formulation is validated by a series of increasingly
      complex canonical problems, including the confined and unconfined compression,
      the Hertz contact problem, and two biphasic indentation tests. As a clinical
      demonstration of the capability of the contact analysis, the gleno-humeral joint
      contact of human shoulders is analyzed using an idealized 3D geometry. In the
      joint, both glenoid and humeral head cartilage experience maximum tensile and
      compressive stresses are at the cartilage-bone interface, away from the center of
      the contact area.

PMID- 17536915
TI  - Speaking up for the health of children.

PMID- 17536916
TI  - Evidence-based practice guidelines and school nursing.
AB  - The use of evidence-based practice (EBP) has become the standard of health care
      practice. Nurses are expected to use best evidence on a wide range of topics, yet
      most nurses have limited time, resources, and/or skills to access and evaluate
      the quality of research and evidence needed to practice evidence-based nursing.
      EBP guidelines allow nurses and other health care workers to have research
      information collected, analyzed, and condensed into specific practice
      recommendations by experts. This article defines EBP guidelines and discusses the
      process of guideline development, including identification of topics, systematic
      literature searches, and evaluation and rating of research. Criteria for
      determining the quality of existing guidelines are reviewed. The steps needed to
      develop EBP guidelines specifically for school nursing are discussed.

PMID- 17536917
TI  - Evidence-based practice guideline: increasing physical activity in schools-
      kindergarten through 8th grade.
AB  - Because of the growing obesity epidemic across all age groups in the United
      States, interventions to increase physical activity and reduce sedentary
      behaviors have become a priority. Evidence is growing that interventions to
      increase physical activity and reduce sedentary behaviors have positive results
      and are generally inexpensive to implement. National and international health
      organizations are calling for a comprehensive approach for reducing obesity in
      children that includes increasing physical activity in the school setting.
      Although the call to increase activity levels in schools is clear, little
      guidance has been given to schools on specific methods to accomplish this task.
      This article provides an overview of an evidence-based guideline developed by a
      physical education teacher and a school nurse to provide inexpensive, easy-to
      implement, effective strategies to increase physical activity in students. Tools
      are also included in the guideline to measure the effectiveness of the
      intervention.

PMID- 17536918
TI  - North Carolina School Nurse Leadership Institute.
AB  - Recognizing that school nurse leaders are essential to the development of school
      nurses, the North Carolina School Nurse Leadership Institute was developed to
      enable school nurse leaders to update and advance their leadership skills. The
      Institute was a collaborative endeavor between the North Carolina Department of
      Health and Human Services, Eastern Area Health Education Center, and East
      Carolina University School of Nursing. School nurse leaders were empowered to
      assume a role in public policy, and they were provided opportunities to network
      with leaders in other counties throughout the state. A combination of face-to
      face and asynchronous discussion via the Internet was used to foster continuous
      rather than episodic learning. Participant evaluations were positive and
      indicated a significant increase in learning in key areas.

PMID- 17536919
TI  - Child health issues in New Zealand: an overview.
AB  - International travel can provide the unique opportunity to experience other
      cultures. For nurses, it can also provide a window through which different health
      care structures and services can be viewed. Many similarities and differences can
      be found between the country visited and the United States in terms of health
      issues, nursing education, roles, and responsibilities. This article explores a
      number of ways health services are provided to school-age children in New
      Zealand. Nearly 20% of New Zealand's population are native Maori people. Not only
      is cultural sensitivity in health service delivery a priority, but the Maori
      people are guaranteed participation in health care decisions by law. School
      nurses in the United States can benefit from examining the models of care used by
      New Zealand nurses for managing the health care needs of school-age children.

PMID- 17536920
TI  - Emergency management of seizures in the school setting.
AB  - Effective seizure management in the school setting is a critical issue for
      students with seizures, as well as their parents, classmates, and school
      personnel. The unpredictable nature of seizures and the potential outcomes of
      experiencing a seizure in school are sources of anxiety for students with
      seizures. The ability to respond appropriately to a seizure is of concern to
      parents and school personnel. Implementation of a seizure emergency treatment
      plan empowers school personnel to quickly treat the child. Diazepam rectal gel is
      commonly used in seizure emergency treatment plans. It is safe and effective in
      terminating seizures and reduces the time to treatment and the need for emergency
      department visits when used in the school setting, and can be administered by
      medical and delegated to trained nonmedical personnel. School nurses should be
      aware of the laws and professional recommendations that pertain to rectal
      medication administration in schools for optimal emergency seizure management.

PMID- 17536921
TI  - School nurses' experience with administration of rectal diazepam gel for
      seizures.
AB  - The purpose of this study was to determine school nurses' knowledge of state and
      school district policies, their experience regarding the administration of rectal
      diazepam gel in the school, and the perceived benefits and barriers of providing
      this treatment. Four hundred nineteen nurses responded to a survey conducted
      during the National Association of School Nurses Annual Meeting. Seventy-one
      (18%) nurses surveyed had administered rectal diazepam gel in a school setting,
      while 54 (13%) nurses reported that either their state practice act or school
      district prohibited them from giving rectal medications in the school. Medication
      administration benefits, such as early intervention for treatment of acute
      seizure emergencies, were noted. Barriers were also identified, with lack of
      privacy as the most frequently listed. Scope of practice as it pertains to
      administering medication in the school and the extent to which delegation of
      duties can be used in the situation of administering rectal medication in a
      seizure emergency remain issues for school nurses.

PMID- 17536922
TI  - An intervention to increase the use of Asthma Action Plans in schools: a MASNRN
      study.
AB  - School nurses, in collaboration with primary care providers (PCPs), can work to
      better manage asthma by using the Asthma Action Plan (AAP) with peak flow
      monitoring. The aim of this pilot study was to determine the effectiveness of an
      intervention to increase the number of AAPs in schools for students with asthma
      by having school nurses provide the students' peak flow measurements to their
      PCPs with a request for an AAP. The study found a significant increase in AAPs
      when school nurses provided PCPs with accurate peak flow data and requested an
      AAP from the PCP than when school nurses requested an AAP via the students'
      parents and did not provide peak flow data to the PCP. This study provided data
      on the importance of collaboration with PCPs in order to affect better care for
      children with asthma.

PMID- 17536923
TI  - Coping strategies used by adolescents during smoking cessation.
AB  - The purpose of this study was to examine coping strategies used by teens as they
      attempted to quit smoking. The teens were attending a school-based cessation
      program titled Quit 2 Win that was offered in four high schools. This study
      examined situations in which teens were tempted to smoke. The study compares
      coping strategies teens reported in resisting smoking with situations where they
      reported lapsing. Participants were interviewed the week of their quit date and
      asked about their state of mind, the availability of cigarettes, and coping
      strategies used to resist smoking. By identifying coping strategies, school
      nurses can develop new interventions for teen smoking cessation.

PMID- 17536925
TI  - Autologous tenocyte therapy using porcine-derived bioscaffolds for massive
      rotator cuff defect in rabbits.
AB  - Large and retracted rotator cuff tendon tears fail to repair or retear after
      surgical intervention. This study attempted to develop novel tissue-engineering
      approaches using tenocyte-seeded bioscaffolds for tendon reconstruction of
      massive rotator cuff tendon defect in rabbits. Porcine small intestine submucosa
      (Restore) and type I/III collagen bioscaffold (ACI-Maix) were chosen as
      bioscaffold carriers for autologous tenocytes. Biological characterization of
      autologous tenocytes was conducted before the implantation. The tenocyte-seeded
      bioscaffolds were implanted as interposition grafts to reconstruct massive
      rotator cuff tendon defects in rabbits. In situ reimplantation of the autologous
      rotator cuff tendon, excised during defect creation, served as a positive
      control. Histological outcomes were analyzed and semi-quantitatively graded at 4
      and 8 weeks after surgery. At 4 weeks, both tenocyte-seeded bioscaffolds
      displayed inflammatory reaction similar to bioscaffold-only cuff reconstruction,
      and the histological grading were inferior to control repair. However, at 8
      weeks, inflammatory reaction of both tenocyte-seeded bioscaffolds were
      dramatically less than with bioscaffold alone. In addition, bioscaffolds seeded
      with tenocytes generated a histological appearance similar to that of the
      positive control. The implantation of autologous tenocytes on collagen-based
      bioscaffolds results in better rotator cuff tendon healing and remodeling than
      with the implantation of bioscaffold alone.

PMID- 17536927
TI  - RamA, a transcriptional regulator, and AcrAB, an RND-type efflux pump, are
      associated with decreased susceptibility to tigecycline in Enterobacter cloacae.
AB  - Tigecycline, a novel broad-spectrum glycylcycline antibiotic, is active against
      many gram-positive and gram-negative bacterial pathogens including most strains
      of Enterobacter cloacae. Recently, however, a few clinical strains of E. cloacae
      with decreased susceptibility to tigecycline were isolated. In this study, two
      tigecycline-susceptible mutants of E. cloacae, GC7696 and GC7697, were obtained
      by transposon mutagenesis of a tigecycline-resistant clinical isolate G946.
      Transposon insertions were mapped to either the acrA or acrB genes. Restoration
      of the original resistant phenotype occurred when GC7696 and GC7697 were
      transcomplemented with a plasmid harboring the intact acrAB region amplified from
      G946. Northern blot analysis of G946 and several other E. cloacae clinical
      strains that exhibited decreased susceptibility to tigecycline, revealed
      increased levels of the acrAB transcript. In addition, overexpression of acrAB
      correlated with increased expression of the ramA gene, whereas the expression of
      another transcriptional activator, marA, was not changed. These results suggest
      that decreased susceptibility to tigecycline in E. cloacae is the result of RamA
      mediated overexpression of the AcrAB efflux pump.

PMID- 17536928
TI  - Characterization of a variant of the SCCmec element in a bloodstream isolate of
      Staphylococcus intermedius.
AB  - Here we report for the first time, a detailed characterization of a variant of
      the SCCmec element, in a methicillin-resistant Staphylococcus intermedius human
      isolate. S. intermedius is a coagulase-positive zoonotic microrganism, recently
      classified as a separate species. In routine clinical laboratory practice, the
      coagulase production is used as criterion of pathogenicity related to S. aureus,
      but S. intermedius is frequently misidentified-being mistaken for S. aureus-and
      consequently its real incidence underestimated. S. intermedius have been found
      only occasionally in human beings, and methicillin-resistance is very rare for
      this organism. Even if the genetic element responsible for methicillin-resistance
      -the mecA gene carried by diverse staphylococcal chromosomal cassettes--has been
      described in various staphylococcal species, the current literature doesn't
      report any case of S. intermedius isolate carrying SCCmec-like elements. Our
      study could be useful to explain the mechanism and routes of transfer of the
      chromosomal cassette carrying the mec complex, among staphylococci.

PMID- 17536926
TI  - Improved cellular infiltration in electrospun fiber via engineered porosity.
AB  - Small pore sizes inherent to electrospun matrices can hinder efficient cellular
      ingrowth. To facilitate infiltration while retaining its extracellular matrix
      like character, electrospinning was combined with salt leaching to produce a
      scaffold having deliberate, engineered delaminations. We made elegant use of a
      specific randomizing component of the electrospinning process, the Taylor Cone
      and the falling fiber beneath it, to produce a uniform, well-spread distribution
      of salt particles. After 3 weeks of culture, up to 4 mm of cellular infiltration
      was observed, along with cellular coverage of up to 70% within the delaminations.
      To our knowledge, this represents the first observation of extensive cellular
      infiltration of electrospun matrices. Infiltration appears to be driven primarily
      by localized proliferation rather than coordinated cellular locomotion. Cells
      also moved from the salt-generated porosity into the surrounding electrospun
      fiber matrix. Given that the details of salt deposition (amount, size, and number
      density) are far from optimized, the result provides a convincing illustration of
      the ability of mammalian cells to interact with appropriately tailored
      electrospun matrices. These layered structures can be precisely fabricated by
      varying the deposition interval and particle size conceivably to produce in vivo
      like gradients in porosity such that the resulting scaffolds better resemble the
      desired final structure.

PMID- 17536929
TI  - Genetic basis for sulfonamide resistance in Bacillus anthracis.
AB  - Natural resistance of field strains of Bacillus anthracis to drugs from the
      sulfonamide class of antimicrobials that act by inhibiting dihydropteroate
      synthase (DHPS) has been reported. Though the structure of B. anthracis DHPS has
      been determined, its connection to the apparent intrinsic sulfonamide resistance
      of the bacterium has not been established. The aim of this study was to determine
      if a connection exists between DHPS and the observed sulfonamide resistance of B.
      anthracis. Microdilution broth assays verified that B. anthracis Sterne is highly
      resistant to a variety of sulfonamides with minimum inhibitory concentrations
      (MICs) exceeding 1250 microg/ml. A putative gene encoding DHPS (folP) was
      amplified from B. anthracis Sterne chromosomal DNA by polymerase chain reaction
      (PCR) and cloned. Sequence comparisons showed 100% identity with DHPSs from
      published genome sequences for various strains of B. anthracis. Additionally,
      expression of folP in B. anthracis Sterne was confirmed. Functionality of the B.
      anthracis DHPS was confirmed by complementation of an Escherichia coli folP
      deletion mutant as well as a standard enzyme assay. Concomitant transfer of high
      level sulfonamide resistance to this mutant along with increased sulfonamide
      IC(50)values for purified B. anthracis DHPS links DHPS to sulfonamide resistance
      in B. anthracis. These findings lay the groundwork that will aid future
      development of antimicrobics that target DHPS to treat anthrax infections.

PMID- 17536930
TI  - Characterization of penicillin intermediate serotypes of Streptococcus pneumoniae
      carried by human immunodeficiency virus-infected adults and healthy children in
      Uganda.
AB  - There are little data on the genetic relatedness between antibiotic-resistant
      pneumococcal isolates colonizing the Ugandan population. Penicillin-intermediate
      pneumococci of serogroups or serotypes rarely or not previously reported as being
      penicillin nonsusceptible were selected out of 166 isolates representing 26
      capsular serogroups or serotypes isolated from Ugandan children in 1995 and human
      immunodeficiency virus (HIV) infected Ugandan adults in 2004-2005. Pairs of
      penicillin-intermediate pneumococci of the same serogroup or serotype present in
      both patient populations were characterized further by pulsed-field gel
      electrophoresis (PFGE) and multilocus sequence typing (MLST). Seven such pairs of
      isolates were found and included serogroups 7, 11, 15B/C, and 16 as well as
      serotypes 13, 21, and 35B. PFGE of these seven pairs showed no clonality between
      serogroups or serotypes, and clonality only within serogroup 11 and serotype 13.
      MLST of the 14 individual isolates revealed 13 different sequence types (STs), 11
      of which had not previously been recorded. Comparisons with all known STs
      revealed that most of these strains were related only to strains of the same
      serotype in other countries, with these related strains frequently also being
      penicillin intermediate. These findings suggest that penicillin nonsusceptibility
      in Uganda is likely due to the introduction of antibiotic-resistant pneumococcal
      clones into Uganda rather than development of resistance within the country.

PMID- 17536931
TI  - Rapid spread in Norway of an erythromycin-resistant pneumococcal clone, despite
      low usage of macrolides.
AB  - During the last 4 years, Norway has experienced an increase in macrolide
      resistance among systemic isolates of Streptococcus pneumoniae. The Norwegian
      reference laboratory for pneumococci received the isolates from over 85% of the
      Norwegian cases of systemic pneumococcal disease in the period studied. To study
      the details of the increased macrolide resistance, all macrolide-resistant
      systemic pneumococcal isolates (410 isolates) collected in the period from 1995
      to 2005 were characterized phenotypically, and a representative selection of 68
      strains was also studied genotypically. The serogroups most frequently associated
      with macrolide resistance in the studied period were 14, 6, 23, 19, and 9. The
      resistance M-type was expressed in 85% of the resistant isolates. Of the 68
      isolates analyzed by multilocus sequence typing, 19 different sequence types
      (STs) were represented, including several of the international resistant clones.
      All but one of the clones appeared at a low frequency; mainly as isolated cases.
      The increase in macrolide resistance seen from 2001 to 2005 proved to be caused
      by ST-9, defined as the England(14)-9 clone by the Pneumococcal Molecular
      Epidemiology Network. All ST-9 isolates tested, carried the mef(A) gene and
      expressed the resistance M-type. This clone first appeared in the Oslo region in
      1993, but was by 2005 isolated from all over the country. Children were
      overrepresented among the cases caused by this clone; however, people aged 20-29,
      possibly involving the parent generation, were also represented at an increased
      frequency. The England(14)-9 clone has been able to spread successfully in the
      Norwegian population despite a relatively low consumption of macrolides.

PMID- 17536932
TI  - Outbreak of Acinetobacter baumannii producing the carbapenem-hydrolyzing
      oxacillinase OXA-58 in Rome, Italy.
AB  - In this study 45 epidemic and sporadic isolates of Acinetobacter baumannii were
      investigated by antimicrobial resistance, integron identifications and
      genotyping. Isolates were genotyped by random amplified polymorphism (RAPD) DNA
      and pulsed-field gel electrophoresis (PFGE). Four different RAPD patterns were
      observed among the isolates of our collection, further discerned in six PFGE
      types. Two prevalent genotypes were identified, one corresponding to a carbapenem
      resistant epidemic clone, causing an outbreak at the intensive care unit of a
      hospital of Rome. Two class 1 integrons, carrying different gene cassette arrays,
      were identified among the two prevalent genotypes. Nucleotide analysis of the
      integron-variable regions revealed the presence of the aacA4, orfO, bla(OXA-20),
      and aacC1, orfX, orfX', aadA1 gene cassette arrays, respectively. All the
      carbapenem resistant strains analyzed in this study carried the bla (OXA-58) gene
      located on plasmids.

PMID- 17536933
TI  - Antimicrobial resistance patterns of Shiga toxin-producing Escherichia coli
      O157:H7 and O157:H7- from different origins.
AB  - Shiga toxin-producing Escherichia coli (STEC) serotypes including O157:H7 (n =
      129) from dairy cows, cull dairy cow feces, cider, salami, human feces, ground
      beef, bulk tank milk, bovine feces, and lettuce; and O157:H7- (n = 24) isolated
      from bovine dairy and bovine feedlot cows were evaluated for antimicrobial
      resistance against 26 antimicrobials and the presence of antimicrobial resistance
      genes (tetA, tetB, tetC, tetD, tetE, tetG, floR, cmlA, strA, strB, sulI, sulII,
      and ampC). All E. coli exhibited resistance to five or more antimicrobial agents,
      and the majority of isolates carried one or more target antimicrobial resistance
      gene(s) in different combinations. The majority of E. coli showed resistance to
      ampicillin, aztreonam, cefaclor, cephalothin, cinoxacin, and nalidixic acid, and
      all isolates were susceptible to chloramphenicol and florfenicol. Many STEC
      O157:H7 and O157:H7-isolates were susceptible to amikacin, carbenicillin,
      ceftriaxone, cefuroxime, ciprofloxacin, fosfomycin, moxalactam, norfloxacin,
      streptomycin, tobramycin, trimethoprim, and tetracycline. The majority of STEC
      O157:H7 (79.8%) and O157:H7- (91.7%) carried one or more antimicrobial resistance
      gene(s) regardless of whether phenotypically resistant or susceptible. Four
      tetracycline resistant STEC O157:H7 isolates carried both tetA and tetC. Other
      tetracycline resistance genes (tetB, tetD, tetE, and tetG) were not detected in
      any of the isolates. Among nine streptomycin resistant STEC O157:H7 isolates,
      eight carried strA-strB along with aadA, whereas the other isolate carried aadA
      alone. However, the majority of tetracycline and streptomycin susceptible STEC
      isolates also carried tetA and aadA genes, respectively. Most ampicillin
      resistant E. coli of both serotypes carried ampC genes. Among sulfonamide
      resistance genes, sulII was detected only in STEC O157:H7 (4 of 80 sulfonamide
      resistant isolates) and sulI was detected in O157:H7- (1 of 16 sulfonamide
      resistant isolates). The emergence and dissemination of multidrug resistance in
      STEC can serve as a reservoir for different antimicrobial resistance genes.
      Dissemination of antimicrobial resistance genes to commensal and pathogenic
      bacteria could occur through any one of the horizontal gene transfer mechanisms
      adopted by the bacteria.

PMID- 17536934
TI  - Microbiologic workload and clinical significance of Streptococcus pneumoniae
      isolated during one week in Spain.
AB  - Most studies reporting Streptococcus pneumoniae (Sp) infections select either
      specific populations/diseases, or refer to a single or a low number of
      institutions. A nationwide point-prevalence study including 147 hospitals from
      which we collected all the isolates of Sp reported in a single week (February 16
      22, 2004). Workload and clinical data were studied, and susceptibility testing
      and serotyping of all isolates were performed. The participating institutions had
      an estimated catchment population of 37,534,750 inhabitants. During the study
      week, microbiology laboratories received 224,956 samples of which 34,647 were
      positive and 360 had S. pneumoniae. Overall, 69% of the isolates were from adults
      (> or = 15 years). Most of the isolates (89%) were considered clinically
      significant. Infection was community-acquired in 88% of infections and
      monomicrobial in 79%. We calculated that S. pneumoniae was isolated 38 times per
      100,000 inhabitants/year and it was present in 1% of all samples with one or more
      bacterial isolates. We also calculated that pneumococcal disease (invasive and
      noninvasive) was present in 34 patients per 100,000 inhabitants/year. Penicillin
      resistance (I+R) was 42%, and erythromycin resistance was 35%. The most frequent
      serotypes were 3, 19F, and 19A. Considering only invasive isolates, the estimated
      coverage of the 7-valent vaccine was 61% in children and 41% in adults, and the
      estimated coverage of the 23-valent vaccine in adults was 79%. A nationwide point
      prevalence study is an efficient tool for surveying pneumococcal infection in a
      large population.

PMID- 17536935
TI  - Streptomycin and chloramphenicol resistance genes in Escherichia coli isolates
      from cattle, pigs, and chicken in Kenya.
AB  - The aims of this study were to determine the genetic basis of streptomycin and
      chloramphenicol resistance in 30 Escherichia coli isolates from food animals in
      Kenya and the role of plasmids in the spread of the resistance. Seven of the 29
      streptomycin-resistant isolates harbored both the strA and strB genes. Twenty-one
      of isolates had the strA, strB, and aadA1 genes. The strA gene was disrupted by a
      functional trimethoprim gene, dfrA14 in 10 of the 21 isolates harboring the three
      streptomycin resistance genes. Physical linkage of intact strA and sul2 genes was
      found in two different plasmids from four isolates. Linkage of cassette-borne
      aadA1 and dfrA1 genes in class 1 integrons was found in two of the isolates.
      Chloramphenicol resistance was due to the gene catA1 in all the chloramphenicol
      resistant isolates. The strB, strA, and catA1 genes were transferable by
      conjugation and this points to the significance of conjugative resistance
      plasmids in the spread and persistence of streptomycin and chloramphenicol
      resistance in food animals in Kenya.

PMID- 17536936
TI  - Risk factors for antimicrobial resistance among fecal Escherichia coli from
      residents on forty-three swine farms.
AB  - Fecal Escherichia coli (n = 555) were isolated from 115 residents on 43 farrow-to
      finish swine farms to determine the prevalence of antimicrobial resistance and
      associated risk factors. Susceptibility to 21 antimicrobials was determined and
      the overall prevalence of antimicrobial resistance was 25.8%. Pair-wise
      difference in prevalences of resistance to individual antimicrobials was
      significant between isolates from residents on farms that fed medicated swine
      rations compared to those that did not (p = 0.013). Cross-resistance among
      antimicrobials of same class and multidrug-resistance were observed. Logistic
      regression models revealed the following risk factors positively associated with
      antimicrobial resistance: use of antimicrobials in pigs on farms; number of hours
      per week that farmers spent in their pig barns; handling of sick pigs; and intake
      of antimicrobials by farm residents. This study indicates that occupational
      exposure of farmers to resistant bacteria and use of antimicrobials in pig
      farming may constitute a source of resistance in humans, although the human
      health impacts of such resistance is unknown. The consumption of antimicrobials
      by farmers appeared to constitute a significant risk for resistance development.
      Fecal E. coli from farm residents may act as a reservoir of resistance genes for
      animal and/or human pathogens.

PMID- 17536937
TI  - The latent structure and coincidence of hypohedonia and schizotypy and their
      validity as indices of psychometric risk for schizophrenia.
AB  - Recent exchanges on the place of hypohedonia within Meehl's theory of
      schizotaxia, schizotypy, and schizophrenia focus on evidence of the taxonicity of
      asociality, not hedonic capacity per se. Two hypotheses were contrasted, one that
      hypohedonia is a nonpathological individual difference variable independent of
      schizotypy, the other that schizotypy and hypohedonia tap independent taxonic
      processes that predict the emergence of positive and negative signs of
      schizophrenia, respectively. Undergraduates (n = 1,543) completed a multifaceted
      measure of schizotypy and hypohedonia. A consecutive subsample of these (n = 284)
      also completed a continuous performance test and the Symptom Checklist 90
      Revised. Independent taxometric analyses (maximum covariance and maximum
      eigenvalue) indicated schizotypy was taxonic and hypohedonia was dimensional.
      Their coincidence was no greater than chance. Schizotypy was associated with
      impaired attention and significant psychological distress, whereas hypohedonia
      was not. Hypohedonia does not behave like a core component of schizotypy.

PMID- 17536938
TI  - Altered emotional decision-making in prisoners with borderline personality
      disorder.
AB  - Previous studies have identified neuropsychological deficits in individuals with
      antisocial personality disorder and/or psychopathy. Few studies have examined
      neuropsychological functioning in individuals with borderline personality
      disorder (BPD), and no studies have yet investigated cognitive and emotional
      function in male prisoners with BPD. In this study, we compared the risky
      decision-making of 17 participants with a history of serious violent or sexual
      offenses and a diagnosis of DSM-IV BPD with that of 17 participants with similar
      offending histories but personality disorders other than BPD. Those with BPD
      exhibited altered processing of information about potential losses (punishment)
      when the probability of gains (reward) was high; they also increased their choice
      of risky options even in circumstances where this was clearly avoidable. These
      data suggest that individuals with a diagnosis of BPD and a history of serious
      offenses have problems integrating different reinforcement signals when choosing
      between risky actions, perhaps reflecting corticolimbic dysfunction as an
      underlying mechanism in BPD.

PMID- 17536939
TI  - Cluster B personality pathology in incarcerated girls: structure, comorbidity,
      and aggression.
AB  - Several studies have linked Cluster B personality pathology to aggression in
      clinical and community samples. However, the structure of Cluster B traits, and
      association to aggression and psychopathology, has yet to be investigated among
      young female offenders. In order to better inform treatments for female
      aggression, we studied 121 incarcerated girls, aged 13 to 19 years, who completed
      a series of self-report inventories that measured overt and relational
      aggression, as well as symptoms of depression and anxiety. Personality was
      assessed through a structured interview. Factor analysis of Cluster B traits
      revealed a three factor solution, with each factor demonstrating a unique pattern
      of association to relational and overt aggression and psychopathology. The
      implications with regard to treatment of personality pathology and aggression in
      the juvenile justice setting are discussed.

PMID- 17536940
TI  - Beyond social deviance: substance use disorders and the dimensions of
      psychopathy.
AB  - High rates of comorbidity between psychopathy and substance use disorders (SUD)
      have long been recognized. However, the extent to which relationships between SUD
      and psychopathy extends beyond shared relationship with general antisociality
      remains undetermined. We examined zero-order and unique relationships between the
      elements of psychopathy and four categories of SUD; alcohol, cannabis, cocaine,
      and opioid dependence. The sample consisted of 399 European American and African
      American male county jail inmates. The relationship between psychopathy and SUD
      extended beyond general antisociality to core features of the psychopathic
      personality. Relationships were relatively stable across ethnicity but were more
      generalized across SUD categories for European American inmates. The relationship
      between SUD and impulsive and irresponsible behavior was most consistent across
      categories of SUD; relationships with other elements of psychopathy varied
      according to category of SUD.

PMID- 17536941
TI  - Impulsivity, anger, and psychopathy: the moderating effect of ethnicity.
AB  - The present research tested the four-factor Psychopathy Checklist: Screening
      Version (PCL:SV) latent variable model for structural invariance across ethnicity
      in a large sample of civil psychiatric patients. In addition, it also examined
      how Barratt (1994) impulsivity and Novaco (1994) anger latent variables were
      related to the psychopathy dimensions within and across ethnicity. The data were
      analyzed with Mplus (Muthen & Muthen, 2001), and results indicated that the four
      factor model was invariant across Caucasian and African American males in terms
      of both item factor loadings and thresholds. However, differential relations
      between the external correlates and the psychopathy dimensions were found across
      groups, suggesting that the association between impulsivity and psychopathy may
      be moderated by ethnicity.

PMID- 17536942
TI  - Comparing individual therapies for personality disordered opioid dependent
      patients.
AB  - Within a psychotherapy development research project, thirty male (50%) and female
      (50%) personality disordered outpatients receiving methadone maintenance were
      randomly assigned to receive one of two 6-month manual-guided individual
      psychotherapies, Dual Focus Schema Therapy (DFST) or 12 Step Facilitation Therapy
      (12FT). All participants met diagnostic criteria for at least one personality
      disorder with antisocial, borderline, avoidant, and dependent being the most
      common. There were no significant differences between the two therapies for
      retention, utilization, or reductions in psychiatric symptoms or psychosocial
      impairment. Both therapy conditions demonstrated significant reductions in
      various severity indicators. Participants demonstrated more rapid decreases in
      the frequency of their substance use over six months of DFST in comparison to
      12FT. DFST also was associated with a stronger therapeutic alliance between
      therapists and participants. Contrary to predictions, 12FT demonstrated better
      reduction of dysphoric affect than did DFST. DFST shows initial promise as the
      first time-limited manual-guided psychotherapeutic approach for the full range of
      personality disorders encountered in substance abuse patients.

PMID- 17536943
TI  - Neuroaffective processing in criminal psychopaths: brain event-related potentials
      reveal task-specific anomalies.
AB  - This study aimed to confirm neuroaffective processing deficits in psychopaths by
      measuring late brain event-related potential (ERP) components and behavior in
      groups of psychopathic and nonpsychopathic inmates of a Singaporean prison while
      they performed two tasks. In a Categorization task, affective stimuli were task
      relevant and required focused attention, while in a Vigilance task, affective
      pictures were presented in the background while participants discriminated
      vertical from oblique lines. Psychopaths showed differences in late positive ERPs
      that were sensitive to affective stimulus properties (valence and arousal) in the
      Categorization, but not in the Vigilance task, suggesting that only under
      conditions of focused attention did psychopaths show a neuroaffective processing
      deficit. In the Categorization task, psychopaths also showed a significantly
      larger prefrontal negative ERP (N350) whose amplitude correlated positively with
      the behavioral facet of psychopathy. In the Vigilance task, psychopaths both
      missed more targets and showed significantly smaller target-evoked parietal ERPs
      when viewing arousing pictures, suggesting their attentional focus was disrupted
      by the affective background.

PMID- 17536944
TI  - Personality-based clusters in bulimia nervosa: differences in clinical variables
      and ecological momentary assessment.
AB  - The present study examined whether personality-based subgroups of bulimic
      individuals differed in eating disorder behavior, comorbid psychopathology,
      treatment history, and momentary assessments of mood and behavior. Participants
      completed an Ecological Momentary Assessment (EMA) protocol for a period of 2
      weeks. Latent profile analysis on the Dimensional Assessment of Personality
      Pathology revealed 3 groupings of bulimic participants: Interpersonal-emotional,
      Stimulus seeking-hostile, and Low personality pathology. The personality-based
      groups differed in histories of mood, anxiety, substance use disorders, features
      of borderline personality disorder, treatment history, and several momentary
      measures. These findings suggest that personality variation within the bulimia
      nervosa diagnostic construct may be associated with meaningful conceptual and
      clinical differences, including daily experiences in the natural environment.

PMID- 17536947
TI  - Aerosol probes of emphysema progression in dogs treated with all trans retinoic
      acid--an exploratory study.
AB  - This study used aerosol probes and lung function tests to investigate whether all
      trans retinoic acid (RA) can reverse experimental emphysema in dogs. Three dogs
      were evaluated with lung mechanics tests, including inspiratory capacity (IC),
      total lung capacity (TLC), and the ratio of forced expired volume in 0.5 sec to
      forced vital capacity (FEV0.5/FVC), an aerosol-derived measure of pulmonary
      airspace size (effective airspace diameter, EAD), and an aerosol-derived measure
      of nonuniform ventilation (aerosol dispersion, AD). Emphysema was induced by
      exposure to aerosolized papain. At 11 or 12 weeks post-papain exposure, dogs
      received oral RA (2 mg/kg/day) for 8 weeks, and were followed for an additional 4
      weeks after stopping RA treatment. In all dogs, lung injury increased in the
      first 11-12 weeks following papain exposure, as evidenced by increasing trends of
      inspiratory capacity IC, TLC, EAD, and AD, and a decreasing trend of FEV0.5/FVC.
      These parameters of lung injury partially and transiently reversed their trends
      between 2 and 6 weeks following the initiation of RA treatment. A sham RA-treated
      group was not studied. However, similar reversals of lung injury were not seen in
      a previous study of dogs treated with papain but not RA, suggesting that RA
      altered emphysema progression in the current study. The limited reversal of lung
      injury in this study contrasts with more pronounced treatment effects seen in
      previous studies with rats. This paper discusses possible reasons for differences
      in these studies, as well as suggestions for improved experimental investigations
      of emphysema therapies.

PMID- 17536948
TI  - Determination of nebulizer droplet size distribution: a method based on impactor
      refrigeration.
AB  - Size distributions of droplets generated by nebulizers are difficult to determine
      because of evaporation after aerosolization. We describe a method whereby a Next
      Generation Pharmaceutical Impactor (NGI; MSP Corporation, Shoreview, MN) is
      refrigerated at 5 degrees C before connecting it to the nebulizer in order to
      ensure an environment inside the NGI at close to 100% relative humidity (RH).
      This, in turn, reduces droplet evaporation between the nebulizer and impaction.
      The method development was performed with a Pari LC Plus jet nebulizer operated
      at 2.0 bar, with the NGI set at a flow rate of 15 L/min and with salbutamol 5.0
      mg/mL as the test solution. The droplet size distributions were expressed in
      terms of mass median aerodynamic diameter (MMAD) and geometric standard deviation
      (GSD). Variation in test conditions showed that the NGI should be cooled for at
      least 90 min, that nebulization should be started within 5 min after removal from
      the refrigerator, and that coating of collecting cups to prevent "bouncing" is
      not necessary. Variation of ambient temperature and humidity had no relevant
      effect on results. MMAD and GSD results showed that refrigeration of the NGI
      resulted in droplet size distributions that are likely to reflect those
      originally delivered at the mouthpiece by the nebulizer. The method was shown to
      be robust, accurate with recovery of test solutions exceeding 99%, reproducible,
      and to be suitable for use with a wide range of commercially available
      nebulizers.

PMID- 17536949
TI  - Educational practice for inhaled treatments in French cystic fibrosis care
      centers.
AB  - Inhaled treatments are very common in cystic fibrosis (CF) patients. We sent a
      questionnaire to the 49 French Cystic Fibrosis Care Centers (CFCCs) to see how
      the inhalation technique of CF patients was initiated and monitored (composition
      and formation of a potential educational team, use of a manual for use, amount of
      devices available for demonstration, education to disinfection procedure,
      realization and frequency of the inhalation technique monitoring, use of the
      patient's own device, and frequency of checking when a pediatric patient
      transfers to an adult CFCC). Results were expressed in percent and compared with
      the test of the difference between two correlated proportions. Education for
      aerosol therapy was not performed in about 20% of the CFCCs. A specific
      educational member was present in 33 CFCCs (68%). CFCCs owned statistically less
      nebulizers for demonstration than other devices. Disinfection advices were always
      given for nebulizers, but less frequently for spacers (80%) and dry powder
      inhalers (50%). The inhalation technique was monitored less than once a year or
      never in 22% of the cases, and rarely with the patient's own material. This
      monitoring was device dependent (56% with nebulizers vs. 76% with the other
      devices, p < 0.05). For nebulizers, monitoring depended on the presence of an
      educational member (p < 0.01) and of a manual for use (p = 0.03). When
      transferring to an adult CFCC, the inhalation technique was checked in less than
      a third of the patients. The inhalation technique is poorly and insufficiently
      initiated and monitored in CF patients. Educational teams and programs are
      urgently required.

PMID- 17536950
TI  - A 6-month inhalation study to characterize the toxicity, pharmacokinetics, and
      pharmacodynamics of human insulin inhalation powder (HIIP) in beagle dogs.
AB  - The purpose of this study was to characterize the toxicity, pharmacokinetics, and
      pharmacodynamics of human insulin inhalation powder (HIIP) in beagle dogs when
      administered daily as an aerosolized dry powder formulation for 26 weeks via head
      only inhalation. Conscious beagle dogs were exposed for 15 mins/day to an air
      control, placebo, maximal placebo (approximately three-fold the placebo dose), or
      one of three doses of HIIP (mean inhaled doses of 80, 240, or 701 microg/kg/day
      for the HIIP-low, HIIP-mid, and HIIP-high dose, respectively), The mass median
      aerodynamic diameters (MMAD) were between 2 and 3 microm and geometric standard
      deviation (GSD) values were approximately 2 across the groups, which is the ideal
      size range for favorable lung deposition. All groups were comprised of four
      dogs/sex, with the air control, HIIP-high, and maximal placebo groups having an
      additional two dogs/sex as recovery subgroups. Concentrations of serum insulin
      and glucose were determined from blood samples obtained following the first and
      last exposure for evaluation of the pharmacokinetics and pharmacodynamics of
      HIIP. Dose-related exposure (C(max), AUC) to inhaled insulin was observed with
      rapid absorption and no apparent gender differences or accumulation after
      repeated inhalation exposures for 26 weeks. The expected pharmacological effect
      of insulin was observed with dose-related decreases in serum glucose levels
      following HIIP administration. There were no toxic effects observed including no
      HIIP or placebo treatment-related effects on mean body weights, absolute body
      weight changes, clinical observations, food consumption, respiratory function
      parameters, ophthalmic examinations, electrocardiograms, heart rates, clinical
      pathology, or urinalysis. Similarly, there were no HIIP or placebo treatment
      related effects on pulmonary assessments that included respiratory function
      parameters, bronchial alveolar lavage assessments, organ weights, or macroscopic
      and microscopic evaluations, including lung cell proliferation indices. HIIP was
      considered to have either low or no immunogenic potential in dogs. The no
      observed-adverse-effect level (NOAEL) and maximum tolerated dose were the average
      inhaled dose of 701 microg insulin/kg/day.

PMID- 17536951
TI  - An analytical technique to recover the third dimension in planar imaging of
      inhaled aerosols--2 estimation of the deposition per airway generation.
AB  - An analytical algorithm has been recently described for converting planar
      scintigraphic images of aerosol distributions in the lungs to an equivalent three
      dimensional (3D) representation. The recovery of the volumetric information has
      opened up to planar imaging the possibility of measuring aerosol deposition per
      airway generation. This paper investigates the accuracy and precision of the
      generation analysis achievable with planar imaging using simulation. Typical
      generation parameters--such as the bronchial and conducting airway deposition
      fractions (BADF and CADF)--have been derived. The accuracy of the technique has
      been measured by the coefficient of variation (COV) of the estimates from the
      known values used in the simulation. The results have also been compared to those
      obtained from 3D imaging (single photon emission computed tomography or SPECT).
      Finally, the technique has been applied to two aerosol studies conducted on a
      healthy volunteer, to demonstrate its implementation on clinical data. The
      accuracy of the BADF and CADF estimates from planar imaging were 42% and 41%,
      respectively; the corresponding values from SPECT were 32% and 22%. In
      conclusion, approximate estimates of airway distribution parameters can be
      derived from planar imaging. However, the errors are significantly higher than
      with SPECT.

PMID- 17536952
TI  - Use of asthmatic pulmonary function test data to predict lung deposition.
AB  - Asthma is a complex disease that alters both breathing patterns and airway
      morphology. Lack of experimental data or model simulations utilizing realistic in
      vivo breathing conditions severely limit the ability to assess the relative risk
      of inhaled pathogens for asthmatics. In this study, a one-dimensional Eulerian
      modeling approach was used to simulate particle deposition in both asthmatic and
      healthy subjects. The model was based on the hypothesis that the component
      reactions of bronchial smooth muscle spasms, submucosal connective tissue
      swelling, and exudation into the airway lumen manifest themselves as altered lung
      function, which can be quantified by the parameters measured in subject pulmonary
      function tests. The asthmatic airway morphology was simulated by altering two
      parameters, functional residual capacity (FRC) and airway resistance (Raw), which
      are increased in asthmatic subjects. The amounts in excess of the healthy case
      were uniquely distributed in the airway generations based on knowledge of the
      changes in the anatomy and physiology of the airway walls during an asthmatic
      episode. Specifically, increased Raw was distributed preferentially in the
      bronchioles and excess FRC was distributed in the pulmonary region. Lung volumes,
      Raw, and breathing conditions of healthy and asthmatic subjects were compiled
      from 18 clinical studies. Significant differences were found between healthy and
      asthmatic Raw, FRC, and tidal volume (TV). In vivo flow fields were simulated
      using population average TV, breathing frequency, and cycle time fractions.
      Results showed that using asthmatic conditions in the simulation increased
      particle deposition over the healthy case by an average of 54% for the range of
      particles tested. This deposition increase was large compared to the difference
      due to intersubject variability of the healthy case. Comparisons to experimental
      data were limited by the number of unreported parameters. This study showed that
      using asthmatic breathing conditions resulted in significantly different particle
      deposition compared to using the controlled breathing patterns reported in
      experimental studies. Therefore, caution should be taken when using experimental
      data to assess particle deposition in vivo if realistic subject breathing is not
      used.

PMID- 17536957
TI  - Vascular smooth muscle NO exposure from intraerythrocytic SNOHb: a mathematical
      model.
AB  - We previously constructed computational models based on the biochemical pathway
      analysis of different nitric oxide (NO) synthase isoforms and found a large
      discrepancy between our predictions and perivascular NO measurements, suggesting
      the existence of nonenzymatic sources of NO. S-nitrosohemoglobin (SNOHb) has been
      suggested as a major source to release NO in the arteriolar lumen and induce
      hypoxic vasodilation. In the present study, we formulated a multicellular
      computational model to quantify NO exposure in arteriolar smooth muscle when the
      NO released by intraerythrocytic SNOHb is the sole NO source in the vasculature.
      Our calculations show an NO exposure of approximately 0.25-6 pM in the smooth
      muscle region. This amount does not account for the large discrepancy we
      encountered regarding perivascular NO levels. We also found that the amount of NO
      delivered by SNOHb to smooth muscle strongly depends on the SNOHb concentration
      and half-life, which further determine the rate of NO release, as well as on the
      membrane permeability of red blood cells (RBCs) to NO. In conclusion, our
      mathematical model predicts that picomolar amounts of NO can be delivered to the
      vascular smooth muscle by intraerythrocytic SNOHb; this amount of NO alone
      appears not sufficient to induce the hypoxic vasodilation.

PMID- 17536958
TI  - Detection and characterization of tumor hypoxia using pO2 histography.
AB  - Data from 125 studies describing the pretreatment oxygenation status as measured
      in the clinical setting using the computerized Eppendorf pO2 histography system
      have been compiled in this article. Tumor oxygenation is heterogeneous and
      severely compromised as compared to normal tissue. Hypoxia results from
      inadequate perfusion and diffusion within tumors and from a reduced O2 transport
      capacity in anemic patients. The development of tumor hypoxia is independent of a
      series of relevant tumor characteristics (e.g., clinical size, stage, histology,
      and grade) and various patient demographics. Overall median pO2 in cancers of the
      uterine cervix, head and neck, and breast is 10 mm Hg with the overall hypoxic
      fraction (pO2 <or= 2.5 mm Hg) being approx. 25%. Metastatic lesions do not
      substantially deviate from the oxygenation status of (their) primary tumors.
      Whereas normal tissue oxygenation is independent of the hemoglobin level over the
      range of 8-15 g/dL, hypoxia is more pronounced in anemic patients and above this
      range in some cancers. Identification of tumor hypoxia may allow an assessment of
      a tumor's potential to develop an aggressive phenotype or acquired treatment
      resistance, both of which lead to poor prognosis. Detection of hypoxia in the
      clinical setting may therefore be helpful in selecting high-risk patients for
      individual and/or more intensive treatment schedules.

PMID- 17536959
TI  - Brain tissue oxygen concentration measurements.
AB  - Brain function depends exquisitely on oxygen for energy metabolism. Measurements
      of brain tissue oxygen tension, by a variety of quantitative and qualitative
      techniques, going back for >50 years, have led to a number of significant
      conclusions. These conclusions have important consequences for understanding
      brain physiology as it is now being explored by techniques such as blood-oxygen
      level-dependent functional magnetic resonance imaging (BOLD fMRI) and near
      infrared spectroscopy (NIRS). It has been known for some time that most of the
      measured oxygen tensions are less than venous pO2 and are distributed in a
      spatially and temporally heterogeneous manner on a microregional scale. Although
      certain large-scale methods can provide reproducible average brain pO2
      measurements, no useful concept of a characteristic oxygen tension or meaningful
      average value for brain tissue oxygen can be known on a microregional level. Only
      an oxygen field exists with large local gradients due to local tissue
      respiration, and the most useful way to express this is with a pO2 distribution
      curve or histogram. The neurons of the brain cortex normally exist in a low
      oxygen environment and on activation are oxygenated by increases in local
      capillary blood flow that lead to increases in hemoglobin saturation and tissue
      oxygen.

PMID- 17536961
TI  - Wounds: an overview of the role of oxygen.
AB  - We sought to review the role of oxygen in wound healing, with an emphasis on the
      role tissue oximetry has played in clinical advances in the care of patients with
      wounds. Oxygen is required for wound healing. Hypoxia sufficient to impair
      healing is common in wounds, frequently resulting from sympathetically induced
      vasoconstriction. Correction or prevention of vasoconstriction, as well as
      provision of increased inspired oxygen in well-perfused patients, has been shown
      in randomized, controlled clinical trials to improve wound outcomes. Our
      understanding of the role of oxygen in wound healing has been fueled by tissue
      oximetry. Advances in technology will lead to further advances in the management
      of patients with wounds.

PMID- 17536960
TI  - Repetitive tissue pO2 measurements by electron paramagnetic resonance oximetry:
      current status and future potential for experimental and clinical studies.
AB  - Tissue oxygen plays a crucial role in maintaining tissue viability and in various
      diseases, including responses to therapy. Useful knowledge has been gained by
      methods that can give limited snapshots of tissue oxygen (e.g., oxygen
      electrodes) or evidence of a history of tissue hypoxia (e.g., EF5) or even
      indirect evidence by monitoring oxygen availability in the circulatory system
      (e.g., NMR methods). Each of these methods has advantages and significant
      limitations. EPR oximetry is a technique for direct measurement of tissue pO2,
      which has several advantages over the other existing methods for applications in
      which the parameter of interest is the pO2 of tissues, and information is needed
      over a time course of minutes to hours, and/or for repetitive measurements over
      days or weeks or years. The aim of this article is to provide an overview of EPR
      oximetry using particulates to readers who are not familiar with this technique
      and its potential in vivo and clinical applications. The data presented here are
      from the experiments currently being carried out in our laboratory. We are
      confident that in vivo EPR oximetry will play a crucial role in the understanding
      and clinical management of various pathologies in the years to come.

PMID- 17536962
TI  - The role of the dorsolateral prefrontal cortex in bimodal divided attention: two
      transcranial magnetic stimulation studies.
AB  - The neural processes underlying the ability to divide attention between multiple
      sensory modalities remain poorly understood. To investigate the role of the
      dorsolateral prefrontal cortex (DLPFC) in bimodal divided attention, we completed
      two repetitive transcranial magnetic stimulation (rTMS) studies. We tested the
      hypothesis that the DLPFC is necessary in the ability to divide attention across
      modalities. This hypothesis originated as a result of a previous fMRI study in
      which the posterior DLPFC was active during a bimodal divided attention condition
      [Johnson, J. A., & Zatorre, R. J. Neural substrates for dividing and focusing
      attention between simultaneous auditory and visual events. Neuroimage, 2006]. In
      the current experiments, two separate groups of subjects underwent 10 min of slow
      rTMS to temporarily disrupt function of the DLPFC. In both groups, the ability to
      divide attention between unrelated auditory and visual stimuli decreased
      following DLPFC disruption compared to control site stimulation. Specifically,
      the ability to divide attention between modalities was hindered, leading to a
      pattern of behavior similar to bimodal selective attention (ability to attend to
      one or the other modality but not both). We discuss possible roles of the
      posterior DLPFC in bimodal divided attention and conclude that the area may be
      functioning to support the increased working memory load associated with divided,
      compared to selective attention.

PMID- 17536963
TI  - Induced gamma band responses predict recognition delays during object
      identification.
AB  - Neural mechanisms of object recognition seem to rely on activity of distributed
      neural assemblies coordinated by synchronous firing in the gamma-band range (>20
      Hz). In the present electroencephalogram (EEG) study, we investigated induced
      gamma band activity during the naming of line drawings of upright objects and
      objects rotated in the image plane. Such plane-rotation paradigms elicit view
      dependent processing, leading to delays in recognition of disoriented objects.
      Our behavioral results showed reaction time delays for rotated, as opposed to
      upright, images. These delays were accompanied by delays in the peak latency of
      induced gamma band responses (GBRs), in the absence of any effects on other
      measures of EEG activity. The latency of the induced GBRs has thus, for the first
      time, been selectively modulated by an experimental manipulation that delayed
      recognition. This finding indicates that induced GBRs have a genuine role as
      neural markers of late representational processes during object recognition. In
      concordance with the view that object recognition is achieved through dynamic
      learning processes, we propose that induced gamma band activity could be one of
      the possible cortical markers of such dynamic object coding.

PMID- 17536964
TI  - Distinct regions of the medial prefrontal cortex are associated with self
      referential processing and perspective taking.
AB  - The medial prefrontal cortex (MPFC) appears to play a prominent role in two
      fundamental aspects of social cognition, that is, self-referential processing and
      perspective taking. However, it is currently unclear whether the same or
      different regions of the MPFC mediate these two interdependent processes. This
      functional magnetic resonance imaging study sought to clarify the issue by
      manipulating both dimensions in a factorial design. Participants judged the
      extent to which trait adjectives described their own personality (e.g., "Are you
      sociable?") or the personality of a close friend (e.g., "Is Caroline sociable?")
      and were also asked to put themselves in the place of their friend (i.e., to take
      a third-person perspective) and estimate how this person would judge the
      adjectives, with the target of the judgments again being either the self (e.g.,
      "According to Caroline, are you sociable?") or the other person (e.g., "According
      to Caroline, is she sociable?"). We found that self-referential processing (i.e.,
      judgments targeting the self vs. the other person) yielded activation in the
      ventral and dorsal anterior MPFC, whereas perspective taking (i.e., adopting the
      other person's perspective, rather than one's own, when making judgments)
      resulted in activation in the posterior dorsal MPFC; the interaction between the
      two dimensions yielded activation in the left dorsal MPFC. These findings show
      that self-referential processing and perspective taking recruit distinct regions
      of the MPFC and suggest that the left dorsal MPFC may be involved in decoupling
      one's own from other people's perspectives on the self.

PMID- 17536965
TI  - Neural dynamics of rejection sensitivity.
AB  - Rejection sensitivity (RS) is the tendency to anxiously expect, readily perceive,
      and intensely react to rejection. This study used functional magnetic resonance
      imaging to explore whether individual differences in RS are mediated by
      differential recruitment of brain regions involved in emotional appraisal and/or
      cognitive control. High and low RS participants were scanned while viewing either
      representational paintings depicting themes of rejection and acceptance or
      nonrepresentational control paintings matched for positive or negative valence,
      arousal and interest level. Across all participants, rejection versus acceptance
      images activated regions of the brain involved in processing affective stimuli
      (posterior cingulate, insula), and cognitive control (dorsal anterior cingulate
      cortex; medial frontal cortex). Low and high RS individuals' responses to
      rejection versus acceptance images were not, however, identical. Low RS
      individuals displayed significantly more activity in left inferior and right
      dorsal frontal regions, and activity in these areas correlated negatively with
      participants' self-report distress ratings. In addition, control analyses
      revealed no effect of viewing negative versus positive images in any of the areas
      described above, suggesting that the aforementioned activations were involved in
      rejection-relevant processing rather than processing negatively valenced stimuli
      per se. Taken together, these findings suggest that responses in regions
      traditionally implicated in emotional processing and cognitive control are
      sensitive to rejection stimuli irrespective of RS, but that low RS individuals
      may activate prefrontal structures to regulate distress associated with viewing
      such images.

PMID- 17536966
TI  - The brain locus of interaction between number and size: a combined functional
      magnetic resonance imaging and event-related potential study.
AB  - Whether the human brain is equipped with a special neural substrate for numbers,
      or rather with a common neural substrate for processing of several types of
      magnitudes, has been the topic of a long-standing debate. The present study
      addressed this question by using functional magnetic resonance imaging (fMRI) and
      event-related potentials (ERPs) together with the size-congruity paradigm, a
      Stroop-like task in which numerical values and physical sizes were varied
      independently. In the fMRI experiment, a region-of-interest analysis of the
      primary motor cortex revealed interference effects in the hemisphere ipsilateral
      to the response hand, indicating that the stimulus-stimulus conflict between
      numerical and physical magnitude is not completely resolved until response
      initiation. This result supports the assumption of distinct comparison mechanisms
      for physical size and numerical value. In the ERP experiment, the cognitive load
      was manipulated in order to probe the degree to which information processing is
      shared across cognitive systems. As in the fMRI experiment, we found that the
      stimulus-stimulus conflict between numerical and physical magnitude is not
      completely resolved until response initiation. However, such late interaction was
      found only in the low cognitive load condition. In contrast, in the high load
      condition, physical and numerical dimensions interacted only at the comparison
      stage. We concluded that the processing of magnitude can be subserved by shared
      or distinct neural substrates, depending on task requirements.

PMID- 17536967
TI  - Grammar or serial order?: discrete combinatorial brain mechanisms reflected by
      the syntactic mismatch negativity.
AB  - If word strings violate grammatical rules, they elicit neurophysiological brain
      responses commonly attributed to a specifically human language processor or
      grammar module. However, an ungrammatical string of words is always also a very
      rare sequence of events and it is, therefore, not always evident whether
      specifically linguistic processes are at work when neurophysiological grammar
      indexes are being reported. We here investigate the magnetic mismatch negativity
      (MNN) to ungrammatical word strings, to very rare grammatical strings, and to
      common grammatical phrases. In this design, serial order mechanism mapping the
      sequential probability of words should neurophysiologically dissociate frequent
      grammatical phrases from both ungrammatical and rare grammatical strings.
      However, if syntax as a discrete combinatorial system is reflected, the
      prediction is that the rare, correctly combined items group with the highly
      frequent grammatical strings and stand out against ungrammatical strings. Using
      magnetoencephalography as a measure of human brain activity, we replicated the
      previously reported syntactic mismatch negativity (sMMN), which distinguishes
      highly unfamiliar ungrammatical word sequences from common grammatical strings.
      Crucially, a significant interaction demonstrated that the sMMN specifically
      distinguished syntactic violations from common grammatical strings, but not
      uncommon from common grammatical word strings. This significant interaction
      argues in favor of a genuinely grammatical origin of the sMMN and provides direct
      neurophysiological evidence for a discrete combinatorial system for word and
      morpheme sequences in the human brain. The data are more difficult to explain in
      the context of serial order models that map co-occurrence probabilities of words.

PMID- 17536968
TI  - When "3" is a jerk and "E" is a king: personifying inanimate objects in
      synesthesia.
AB  - We report a case study of an individual (TE) for whom inanimate objects, such as
      letters, numbers, simple shapes, and even furniture, are experienced as having
      rich and detailed personalities. TE reports that her object-personality pairings
      are stable over time, occur independent of her intentions, and have been there
      for as long as she can remember. In these respects, her experiences are
      indicative of synesthesia. Here we show that TE's object-personality pairings are
      very consistent across test-retest, even for novel objects. A qualitative
      analysis of TE's personality descriptions revealed that her personifications are
      extremely detailed and multi-dimensional, and that her personifications of
      familiar and novel objects differ in specific ways. We also found that TE's eye
      movements can be biased by the emotional associations she has with letters and
      numbers. These findings demonstrate that synesthesia can involve complex semantic
      personifications, which can influence visual attention. Finally, we propose a
      neural model of normal personification and the unusual personifications that
      accompany object-personality synesthesia.

PMID- 17536969
TI  - Individual differences in the effects of perceived controllability on pain
      perception: critical role of the prefrontal cortex.
AB  - The degree to which perceived controllability alters the way a stressor is
      experienced varies greatly among individuals. We used functional magnetic
      resonance imaging to examine the neural activation associated with individual
      differences in the impact of perceived controllability on self-reported pain
      perception. Subjects with greater activation in response to uncontrollable (UC)
      rather than controllable (C) pain in the pregenual anterior cingulate cortex
      (pACC), periaqueductal gray (PAG), and posterior insula/SII reported higher
      levels of pain during the UC versus C conditions. Conversely, subjects with
      greater activation in the ventral lateral prefrontal cortex (VLPFC) in
      anticipation of pain in the UC versus C conditions reported less pain in response
      to UC versus C pain. Activation in the VLPFC was significantly correlated with
      the acceptance and denial subscales of the COPE inventory [Carver, C. S.,
      Scheier, M. F., & Weintraub, J. K. Assessing coping strategies: A theoretically
      based approach. Journal of Personality and Social Psychology, 56, 267-283, 1989],
      supporting the interpretation that this anticipatory activation was associated
      with an attempt to cope with the emotional impact of uncontrollable pain. A
      regression model containing the two prefrontal clusters (VLPFC and pACC)
      predicted 64% of the variance in pain rating difference, with activation in the
      two additional regions (PAG and insula/SII) predicting almost no additional
      variance. In addition to supporting the conclusion that the impact of perceived
      controllability on pain perception varies highly between individuals, these
      findings suggest that these effects are primarily top-down, driven by processes
      in regions of the prefrontal cortex previously associated with cognitive
      modulation of pain and emotion regulation.

PMID- 17536970
TI  - Functional interactions during the retrieval of conceptual action knowledge: an
      fMRI study.
AB  - Impaired retrieval of conceptual knowledge for actions has been associated with
      lesions of left premotor, left parietal, and left middle temporal areas [Tranel,
      D., Kemmerer, D., Adolphs, R., Damasio, H., & Damasio, A. R. Neural correlates of
      conceptual knowledge for actions. Cognitive Neuropsychology, 409-432, 2003]. Here
      we aimed at characterizing the differential contribution of these areas to the
      retrieval of conceptual knowledge about actions. During functional magnetic
      resonance imaging (fMRI), different categories of pictograms (whole-body actions,
      manipulable and nonmanipulable objects) were presented to healthy subjects. fMRI
      data were analyzed using SPM2. A conjunction analysis of the neural activations
      elicited by all pictograms revealed ( p<.05, corrected) a bilateral inferior
      occipito-temporal neural network with strong activations in the right and left
      fusiform gyri. Action pictograms contrasted to object pictograms showed
      differential activation of area MT+, the inferior and superior parietal cortex,
      and the premotor cortex bilaterally. An analysis of psychophysiological
      interactions identified contribution-dependent changes in the neural responses
      when pictograms triggered the retrieval of conceptual action knowledge:
      Processing of action pictograms specifically enhanced the neural interaction
      between the right and left fusiform gyri, the right and left middle temporal
      cortices (MT+), and the left superior and inferior parietal cortex. These results
      complement and extend previous neuropsychological and neuroimaging studies by
      showing that knowledge about action concepts results from an increased coupling
      between areas concerned with semantic processing (fusiform gyrus), movement
      perception (MT+), and temporospatial movement control (left parietal cortex).

PMID- 17536971
TI  - Magnetic stimulation of the right visual cortex impairs form-specific priming.
AB  - Recent evidence suggests that priming of objects across different images
      (abstract priming) and priming of specific images of an object (form-specific
      priming) are mediated by dissociable neural processing subsystems that operate in
      parallel and are predominantly linked to left and right hemispheric processing,
      respectively [Marsolek, C. J. Dissociable neural subsystems underlie abstract and
      specific object recognition. Psychological Science, 10, 111-118, 1999]. Previous
      brain imaging studies have provided important information about the
      neuroanatomical regions that are involved in form-specific and abstract priming;
      however, these techniques did not fully establish the functional significance of
      priming-related changes in cortical brain activity. Here, we used repetitive
      transcranial magnetic stimulation (rTMS) in order to establish the functional
      role of the right occipital cortex in form-specific priming [Kroll, N. E. A.,
      Yonelinas, A. P., Kishiyama, M. M., Baynes, K., Knight, R. T., & Gazzaniga, M. S.
      The neural substrates of visual implicit memory: Do the two hemispheres play
      different roles? Journal of Cognitive Neuroscience, 15, 833-842, 2003]. Compared
      to no TMS and sham TMS, rTMS of the right occipital cortex disrupted immediate
      form-specific priming in a semantic categorization task. Left occipital rTMS, on
      the other hand, had no converse effect on abstractive priming. Abstract priming
      may involve deeper semantic processing and may be unresponsive to magnetic
      stimulation of a single cortical locus. Our TMS results show that form-specific
      priming relies on a visual word-form system localized in the right occipital
      lobe, in line with the predictions from divided visual field behavioral studies
      [Marsolek, 1999].

PMID- 17536972
TI  - Age differences in deactivation: a link to cognitive control?
AB  - The network of regions shown by functional imaging studies to be deactivated by
      experimental tasks relative to nominally more passive baselines (task < baseline)
      may reflect processes engaged during the resting state or "default mode."
      Deactivation may result when attention and resources are diverted from default
      mode processes toward task processes. Aging is associated with altered patterns
      of deactivation which may be related to declining resources, difficulties with
      resource allocation, or both. These possibilities predict that greater task
      demand, which increases deactivation levels in younger adults, should exacerbate
      age-related declines in allocating resources away from the default mode. The
      present study investigated the magnitude and temporal properties of deactivations
      in young and older adults during tasks that varied in their demand for cognitive
      control. Two versions of a verb generation task that varied in their demand for
      selection among competing alternatives were compared to word reading and a
      fixation baseline condition. Consistent with our hypothesis, greater
      deactivations were found with increasing demand. Young and older adults showed
      equivalent deactivations in the minimal selection condition. By contrast, age
      differences in both the magnitude and time course of deactivation increased with
      selection demand: Compared to young adults', older adults' deactivation response
      showed less sensitivity to demand. Demand-related changes in deactivation
      magnitude correlated with performance changes, suggesting that individual and
      group differences in deactivation have functional significance.

PMID- 17536973
TI  - Modeling orienting behavior and its disorders with "ecological" neural networks.
AB  - Computational modeling is a useful tool for spelling out hypotheses in cognitive
      neuroscience and testing their predictions in artificial systems. Here we
      describe a series of simulations involving neural networks that learned to
      perform their task by self-organizing their internal connections. The networks
      controlled artificial agents with an orienting eye and an arm. Agents saw objects
      with various shapes and locations and learned to press a key appropriate to their
      shape. The results showed the following: (1) Despite being able to see the entire
      visual scene without moving their eye, agents learned to orient their eye toward
      a peripherally presented object. (2) Neural networks whose hidden layers were
      previously partitioned into units dedicated to eye orienting and units dedicated
      to arm movements learned the identification task faster and more accurately than
      did nonmodular networks. (3) Nonetheless, even nonmodular networks developed a
      similar functional segregation through self-organization of their hidden layer.
      (4) After partial disconnection of the hidden layer from the input layer, the
      lesioned agents continued to respond accurately to single stimuli, wherever they
      occurred, but on double simultaneous stimulation they oriented toward and
      responded only to the right-sided stimulus, thus simulating extinction/neglect.
      These results stress the generality of the advantages provided by orienting
      processes. Hard-wired modularity, reminiscent of the distinct cortical visual
      streams in the primate brain, provided further evolutionary advantages. Finally,
      disconnection is likely to be a mechanism of primary importance in the
      pathogenesis of neglect and extinction symptoms, consistent with recent evidence
      from animal studies and brain-damaged patients.

PMID- 17536974
TI  - Grammatical processing without semantics? An event-related brain potential study
      of preschoolers using jabberwocky sentences.
AB  - Behavioral studies have demonstrated that children develop a nearly adult-like
      grammar between 36 and 42 months, but few studies have addressed how the child's
      brain processes semantic versus syntactic information. In previous research,
      Silva-Pereyra and colleagues showed that distinct event-related potentials (ERPs)
      are elicited by semantic and syntactic violations in sentences in children as
      young as 30, 36, and 48 months, following the patterns displayed by adults. In
      the current study, we examined ERPs to syntactic phrase structure violations in
      real and jabberwocky sentences in 36-month-old children. Jabberwocky sentences
      are sentences in which content (open-class) words are replaced by pseudowords
      while function (closed-class) words are retained. Results showed that
      syntactically anomalous real sentences elicited two positive ERP effects: left
      distributed effects from 500 to 750 msec and 1050 to 1300 msec, whereas
      syntactically anomalous jabberwocky sentences elicited two negative ERP effects:
      a left-distributed effect from 750 to 900 msec and a later broadly distributed
      effect from 950 to 1150 msec. The results indicate that when preschoolers process
      real English sentences, ERPs resembling the positive effects previously reported
      for adults are noted, although at longer latencies and with broader scalp
      distributions. However, when preschoolers process jabberwocky sentences with
      altered lexical-semantic content, a negative-going ERP component similar to one
      typically associated with the extraction of meaning is noted.

PMID- 17536975
TI  - In vivo selection and chemoprotection after drug resistance gene therapy in a
      nonmyeloablative allogeneic transplantation setting in dogs.
AB  - We have previously demonstrated successful in vivo selection, chemoprotection,
      and modulation of donor chimerism in dogs that received myeloablative allogeneic
      stem cell transplantation with cells expressing the P140K mutant of the DNA
      repair enzyme methylguanine methyltransferase (MGMTP140K). Here, we wished to
      investigate whether in vivo selection, chemoprotection, and modulation of donor
      chimerism could also be achieved after nonmyeloablative transplantation, which
      could allow for less toxic transplantation regimens for patients with malignant
      and genetic diseases. Three dogs received a nonmyeloablative conditioning regimen
      and infusion of allogeneic stem cells transduced with MGMTP140K. All three dogs
      had stable gene marking and donor chimerism before receiving a course of O(6) 
      benzylguanine (O(6) BG)/1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) between days
      210 and 589 after transplantation. One to four doses led to a marked increase in
      gene marking in all dogs. Furthermore, the transduced cells conferred
      chemoprotection and prevented severe neutropenia. Our results suggest that drug
      resistance gene therapy is feasible and safe in the nonmyeloablative
      transplantation setting.

PMID- 17536976
TI  - Effective treatment of human breast tumor in a mouse xenograft model with herpes
      simplex virus type 1 specifying the NV1020 genomic deletion and the gBsyn3
      syncytial mutation enabling high viral replication and spread in breast cancer
      cells.
AB  - A new oncolytic and fusogenic herpes simplex virus type 1 (HSV-1) was constructed
      on the basis of the wildtype HSV-1(F) strain. To provide for safety and tumor
      selectivity, the virus carried a large deletion including one of the two alpha4,
      gamma(1)34.5, alpha0 genes and the latency-associated transcript region. The
      gamma(1)34.5 gene, a major neurovirulence factor, was replaced by a gene cassette
      constitutively expressing the red fluorescent protein gene. Homologous
      recombination was used to transfer the fusogenic gBsyn3 mutation to the viral
      genome to produce the OncSyn virus. OncSyn causes extensive virus-induced cell
      fusion (syncytia) and replicates to higher titers than the parental Onc and HSV
      1(F) strains in breast cancer cells. Biochemical analysis revealed that the
      OncSyn virus retains a stable genome and expresses all major viral glycoproteins.
      A xenograft mouse model system using MDA-MB-435S-luc (MM4L) human breast cancer
      cells constitutively expressing the luciferase gene implanted within the
      interscapular region of animals was used to test the ability of the virus to
      inactivate breast tumor cells in vivo. Seventy-two mice bearing MM4L breast
      cancer xenografts were randomly divided into three groups and given two rounds of
      three consecutive intratumoral injections of OncSyn, inactivated OncSyn, or
      phosphate-buffered saline 3 days apart. A single round of virus injections
      resulted in a drastic reduction of tumor sizes (p <or= 0.0001) and diminution of
      chemiluminescence emitted by the cancer cells (p <or= 0.0002). This effect was
      enhanced by a second round of virus injections into the tumors 3 days after the
      first round (p <or= 0.0001). Systematic necropsy and pathological evaluation of
      the primary tumors revealed that the single round of injections resulted in
      extensive necrosis of tumor cells (p <or= 0.0001), which was enhanced by the
      second round of injections (p <or= 0.0002). Internal organs were not affected by
      virus inoculation. Mouse weights were not significantly impacted by any treatment
      during the course of the entire study (p = 0.46). These results show that the
      attenuated, fusogenic, and oncolytic HSV-1(F) virus strain OncSyn may effectively
      treat human breast tumors in vivo.

PMID- 17536978
TI  - Rapid response systems: have we MET the need?

PMID- 17536979
TI  - Relationship between tissue hypoxia and apoptosis: a preliminary observational
      study.
AB  - AIMS: This observational study examined the relationship between tissue hypoxia
      (PO2 of 30mmHg and 15mmHg) and the development of dysoxia and apoptosis. METHODS:
      28 Sprague-Dawley rats were studied in three groups. Group 1 had no interventions
      (controls; n=6). Graded hypoxia was induced in Group 2 (n =13) and Group 3 (n =9)
      to achieve a subcutaneous PO2 of < 30mmHg (20 minutes) followed by < 15mmHg (20
      minutes). In addition, Group 3 received reoxygenation to baseline after hypoxia.
      Ileal and cutaneous tissues were assessed for apoptosis (by histology, TUNEL and
      immunohistochemistry for caspase-3) and dysoxia (tissue lactate concentration and
      energy charge). RESULTS: An interstitial PO2 < 30mmHg led to statistically
      significant elevations in skin and gut lactate concentrations from baseline (mean
      +/-SD: skin, 0.2+/-0.07 to 0.6 +/-0.3mmol/ kg wet weight, P < 0.01; gut, 1 +/-0.7
      to 6 +/-4mmol/kg wet weight, P<0.05). With hypoxia, there was an increase in
      apoptosis scores in the gut villi from baseline in the experimental arms (17% +/
      21% to 53% +/-58%, P<0.05 in Group 2; 9% +/-5% to 27%+/-12%, P < 0.05 in Group
      3). There was no significant increase in skin apoptosis. No significant
      correlation was noted between gut lactate concentrations and gut apoptosis (r= 
      0.28). CONCLUSIONS: In this pilot study, reductions in PO2 to <30mmHg were
      associated with significant dysoxic changes in the gut and skin. No clear tissue
      PO2 threshold for the initiation of apoptosis was identified. Further studies
      with refinements to the experimental model may allow more precise identification
      of PO2 thresholds that are critical for the development of apoptosis.

PMID- 17536980
TI  - Prospective evaluation of procalcitonin in sepsis in the Illawarra area of
      Australia: PEPSIA study.
AB  - INTRODUCTION: Procalcitonin (PCT) is a precursor of the hormone calcitonin and
      has been proposed as a marker of infection in critically ill patients. We
      evaluated the role of procalcitonin in the early detection of sepsis in an
      Australian intensive care-high dependency unit (ICU/HDU). METHODS: This
      prospective observational study enrolled 204 consecutive patients admitted to the
      ICU/HDU of Wollongong Hospital, NSW, over a 3-month period, October to December
      2001. Of the 204, 172 (84%) were included in the final analysis. Patient
      demographic data, serum PCT levels and the vital signs required to score the
      criteria for systemic inflammatory response syndrome (SIRS) and sepsis were
      recorded daily until the patient left the ICU. Cultures were obtained when
      clinically indicated. RESULTS: PCT measurement appears a useful screening test
      for sepsis with a cut-off value > 0.85 ng/dL. At levels >10 ng/dL, its diagnostic
      accuracy improves significantly. PCT level was able to discriminate between
      sepsis and nonsepsis, and between septic shock and non-septic shock. However, it
      failed to discriminate well between bacterial and non-bacterial SIRS with a 95%
      CI for area under the receiver operating characteristic curve of 0.59-0.76.
      CONCLUSIONS: The use of PCT as a screening test (PCT >0.85ng/dL) in conjunction
      with traditional criteria is of value in the early diagnosis of bacterial sepsis
      in suspected cases in the ICU. PCT appears to be a reliable diagnostic test for
      bacterial sepsis at levels > 10 ng/dL.

PMID- 17536981
TI  - Effect of changes in syringe driver height on flow: a small quantitative study.
AB  - OBJECTIVE: To quantify flow irregularities in drug delivery caused by vertical
      displacement of syringe pumps. METHODS: A bench experiment was performed to
      quantify the effect of height on pumps used in our intensive care and theatre
      settings. A standard syringe pump and line set loaded with a dye solution was run
      through a graduated length of tubing, and the effect of changing pump height
      quantified by measuring progress down the tubing over time. RESULTS: A 30 cm
      elevation produced significant drug delivery boluses - up to seven times the
      programmed rate at 2mL/h. Delivery rate increased in inverse proportion to the
      programmed rate, as did the time taken to return to the programmed rate. Lowering
      the pump 30 cm resulted in no-flow times of up to 180 seconds at a flow rate of
      2mL/h - again inversely proportional to programmed rate. CONCLUSIONS: Vertical
      displacement of a common syringe pump by 30 cm produced significant bolus and
      cessation phenomena. These findings confirm the observations of previous authors
      and also demonstrate significant flow irregularities with smaller vertical
      displacements than previously tested. Further testing with other brands of pumps
      is required before a solution to this clinically important problem may be
      approached.

PMID- 17536982
TI  - A clinical audit of the efficacy of tegaserod as a prokinetic agent in the
      intensive care unit.
AB  - OBJECTIVE: To formally document the effectiveness of tegaserod as a prokinetic
      agent in intensive care patients. METHODS: The audit was designed in consultation
      with the Northern Territory Drug and Therapeutics Committee. Tegaserod was added
      to the feeding protocol and prokinetic algorithm in the ICU, and a prospective
      audit was performed of patients receiving the medication between May and
      September 2006. RESULTS: Over the 5-month period, 40 patients received tegaserod
      after failing to respond to two doses of metoclopramide. Median daily volume of
      gastric aspirate was reduced from 1220mL in the 24 hours before tegaserod to
      887.5mL in the first 24 hours after its introduction, and to 280mL in the second
      24 hours (P=0.01 and P<0.001, respectively). Tegaserod was an effective
      prokinetic agent in 85% (34) patients. Attributable diarrhoea occurred in 13% (5)
      patients, but did not require intervention. CONCLUSIONS: Tegaserod is an
      effective alternative prokinetic agent for ICU patients with a safer side-effect
      profile. We believe it warrants further investigation.

PMID- 17536983
TI  - The medical emergency team and end-of-life care: a pilot study.
AB  - OBJECTIVES: To assess the characteristics of patients who died in a teaching
      hospital and the role of the medical emergency team (MET) in their end-of-life
      care. METHODS: This was a retrospective analysis of 105 deaths over the month of
      May 2005 by a blinded investigator, who documented patient age, parent hospital
      unit, comorbidities, presence and timing of not-for-resuscitation (NFR)
      designation, and presence and timing of first MET review. We analysed differences
      between medical versus surgical patients, NFR versus non-NFR patients, and MET
      reviewed versus non-MET-reviewed patients. RESULTS: Of the 105 patients who died,
      80 were medical patients and 25 were surgical patients. Five patients were not
      designated NFR at the time of death, and three of these had antecedent MET
      criteria in the 24 hours before death. Of the 100 patients who were designated
      NFR at the time of death, 35 received a MET call during their admission. Of the
      35 MET calls, 10 occurred on the same day as the patient's death, and 12 on the
      same day as the NFR designation. Documentation of NFR status occurred later in
      the admission for patients who received a MET call than for those who did not
      receive a MET call (mean +/-SD, 13.3 +/-16.1 versus 5.3 +/-10.8 days after
      admission; P = 0.003). Hypotension, hypoxia and tachypnoea were the most common
      MET triggers, and pulmonary oedema, pneumonia and acute coronary syndromes were
      the most common reasons for the deterioration in the patient's condition.
      Following the MET review, patients were admitted to the ICU and newly classified
      as NFR in 15 and nine of the 35 MET calls, respectively. CONCLUSIONS: Most
      patients who died in our hospital were designated NFR at the time of death. A
      third of these patients were seen by the MET before death. In about 10% of cases,
      the MET participated in the decision to designate the patient NFR.

PMID- 17536984
TI  - The antimicrobial effect of heparin on common respiratory pathogens.
AB  - AIM: The mucolytic, anticoagulative, anti-inflammatory and neo-angiogenic
      properties of inhaled heparin may benefit patients with burns and cystic
      fibrosis. We assessed the antibacterial effects of unfractionated heparin.
      METHODS: Stored clinical isolates of Acinetobacter baumannii (n =4), Candida
      albicans (n = 5), Haemophilus influenzae (n =5), Klebsiella pneumoniae (n =4),
      methicillin-resistant Staphylococcus aureus (n=3), Pseudomonas aeruginosa (n =
      2), and Streptococcus pneumoniae (n = 7) were subcultured on horse blood agar,
      incubated at 35 degrees C overnight, then inoculated into trypticase soy broth to
      a density of 1 McFarland standard. Dilutions of unfractionated heparin
      (containing 250- 7500 U) and 100 microL of the 1.0 McFarland standard broth were
      incubated at 35 degrees C overnight in microtitre plates and then subcultured on
      horse blood agar using 1 microL standard loops. Colonies (representing viable
      organisms) were counted. RESULTS: Heparin produced dose-dependent growth
      inhibition of three of seven S. pneumoniae isolates (complete inhibition at 2500U
      dose per 200 microL) and one of five H. influenzae isolates (complete inhibition
      at 7500 U dose per 200 microL), but no inhibition of other isolates. CONCLUSIONS:
      Unfractionated heparin is unlikely to have antibacterial effects because of its
      unpredictable inhibition of growth of common respiratory pathogens.

PMID- 17536985
TI  - A sustained reduction in the transmission of methicillin resistant Staphylococcus
      aureus in an intensive care unit.
AB  - INTRODUCTION: In 2001, screening for methicillin-resistant Staphylococcus aureus
      (MRSA) was initiated in the intensive care unit at Dandenong Hospital, Melbourne,
      Australia. This followed the identification of a clinical isolate of vancomycin
      intermediate-resistant S. aureus (VISA). Contact precautions for patients
      colonised or infected with MRSA or VISA were utilised, together with the
      promotion of hand hygiene and additional environmental cleaning. In 2004, poor
      compliance with hand-hygiene requirements was recognised as potentially
      contributing to the inability to control MRSA transmission. METHODS: A renewed
      campaign was introduced in 2004, aimed at improving hand hygiene in the ICU. This
      involved the introduction of an alcoholic chlorhexidine handrub station on a
      trolley at the door of the ICU. Use of alcoholic chlorhexidine handrub was
      mandated for existing and visiting staff to the ICU, and its use was actively
      promoted by all ICU staff. RESULTS: From 2001 to 2004, the average monthly
      acquisition of MRSA in the unit was 15.2 patients per 1000 occupied bed days
      (OBD). Following the implementation of the campaign aimed at visiting staff, the
      average acquisition of MRSA dropped to 3.2 patients per 1000 OBD. CONCLUSIONS:
      Ownership of hand-hygiene responsibility for patients' protection appeared to
      contribute to the success of this initiative. The ability to sustain the
      excellent result was enhanced by the unit leadership and the empowerment of the
      nurse at the bedside to be the patient's advocate. Nurses, who are at the patient
      bedside 24 hours per day, 7 days per week, are well positioned to reinforce
      appropriate hand hygiene.

PMID- 17536986
TI  - Effect of midazolam versus propofol sedation on markers of neurological injury
      and outcome after isolated severe head injury: a pilot study.
AB  - BACKGROUND: Midazolam and propofol are sedative agents commonly administered to
      patients with brain injury. We compared plasma concentrations of glial cell
      S100beta protein and nitric oxide (NO) between patients who received midazolam
      and those who received propofol sedation after severe brain injury, and
      investigated the association between S100beta and NO concentrations and
      neurological outcome. DESIGN: 28 patients with severe head injury (Glasgow Coma
      Score <9) who required sedation and ventilation were randomly assigned to receive
      midazolam (n =15) or propofol (n = 13) based sedation. Blood samples were drawn
      daily for 5 days for estimation of S100beta and NO concentrations. Neurological
      outcome was assessed 3 months later as good (Glasgow Outcome Score [GOS], 4-5) or
      poor (GOS, 1-3). RESULTS: A good neurological outcome was observed in 8/15
      patients (53%) in the midazolam group and 7/13 patients (54%) in the propofol
      group. Patients with a poor outcome had higher serum S100beta concentrations on
      ICU admission and on Days 1-4 in the ICU than those with a good outcome (mean
      [SD] on Day 1, 0.99 [0.81] v 0.41 [0.4] microg/L; Day 2, 0.80 [0.81] v 0.41
      [0.24] microg/L; Day 3, 0.52 [0.55] v 0.24 [0.25] microg/L; and Day 4, 0.54
      [0.43] v 0.24 [0.35] microg/L; P<0.05). There was no significant difference on
      Day 5. Plasma NO concentrations were not associated with outcome. In subgroup
      analysis, there was no difference in S100beta and NO concentrations between
      patients with a good outcome versus those with a poor outcome in either the
      midazolam or propofol group. CONCLUSIONS: Plasma concentrations of markers of
      neurological injury in patients with severe head injury were similar in those who
      received midazolam sedation and those who received propofol. Patients who had a
      poor neurological outcome at 3 months had consistently higher serum S100beta
      concentrations during the initial 4 days after injury than patients who had a
      good outcome.

PMID- 17536987
TI  - The long-term outcome of children managed with extracorporeal life support: an
      institutional experience.
AB  - OBJECTIVE: To evaluate the long-term functional status and quality of life of
      infants and children who have received extracorporeal life support (ECLS), and to
      determine how and when death occurred. DESIGN: Long-term, prospective follow-up
      study. SETTING: 16-bed paediatric intensive care unit in a university teaching
      hospital. PARTICIPANTS: All children who received ECLS in the period April 1988
      to October 2000 in the paediatric ICU at the Royal Children's Hospital,
      Melbourne, VIC. METHODS: The records of all 224 children who had received ECLS
      were reviewed, and functional status and quality of life were assessed through
      interview with each child's parent or guardian for those who had survived.
      RESULTS: Follow-up information was available for 211 children at a median of 7.2
      years (range, 3.9 months to 12.6 years) after admission to the paediatric ICU.
      Sixty-nine children were alive at follow-up, 96% of whom were likely to lead an
      independent existence. Of the 142 deaths, 123 occurred in the paediatric ICU: 74
      were due to elective withdrawal of therapy for poor prognosis, and eight for
      brain death; 30 were disease-related; seven were ECLSrelated; and four were due
      to sepsis. CONCLUSIONS: ECLS is a complex therapy which has been used in
      Australian children for 18 years; a third of children survived long term, and 96%
      of these had a favourable outcome.

PMID- 17536988
TI  - Methaemoglobinaemia: an explosive case.
AB  - Methaemoglobinaemia is an important perturbation to recognise, as untreated it
      may cause severe tissue hypoxia and cell death. We describe a case of
      methaemoglobinaemia acquired in an unusual manner, during an explosion at an
      explosives manufacturing plant.

PMID- 17536989
TI  - Group B streptococcal meningitis in a middle-aged woman.
AB  - Group B streptococcal (GBS) infections are increasing in incidence as a cause of
      serious disease in the adult population. Risk factors for this infection include
      age, diabetes mellitus, liver disease, history of stroke, breast cancer and HIV
      infection, which are all becoming more common. We report a patient with severe
      GBS meningitis who made a good recovery following appropriate treatment, despite
      a delay in specific diagnosis of the organism. We believe this to be the first
      case of GBS meningitis in a non-pregnant adult in Australia or New Zealand to be
      reported in the literature.

PMID- 17536990
TI  - Cerebral fat embolism syndrome causing brain death after long-bone fractures and
      acetazolamide therapy.
AB  - A 19-year-old woman with multiple fractures and mild brain injury developed
      severe cerebral fat embolism syndrome after "damage control" orthopaedic surgery.
      Acetazolamide therapy to manage ocular trauma, in association with
      hyperchloraemia, caused a profound metabolic acidosis with appropriate
      compensatory hypocapnia. During ventilator weaning, unexpected brainstem coning
      followed increased sedation and brief normalisation of arterial carbon dioxide
      concentration. Autopsy found severe cerebral fat embolism and brain oedema. In
      patients with multiple trauma, cerebral fat embolism syndrome is difficult to
      diagnose, and may be more common after delayed fixation of long-bone fractures.
      Acetazolamide should be used with caution, as sudden restoration of normocapnia
      during compensated metabolic acidosis in patients with raised intracranial
      pressure may precipitate coning.

PMID- 17536991
TI  - Statistics in review. Part 2: generalised linear models, time-to-event and time
      series analysis, evidence synthesis and clinical trials.
AB  - In Part I, we reviewed graphical display and data summary, followed by a
      consideration of linear regression models. Generalised linear models, structured
      in terms of an exponential response distribution and link function, are now
      introduced, subsuming logistic and Poisson regression. Time-to-event ("survival")
      analysis is developed from basic principles of hazard rate, and survival,
      cumulative distribution and density functions. Semi-parametric (Cox) and
      parametric (accelerated failure time) regression models are contrasted. Time
      series analysis is explicated in terms of trend, seasonal, and other cyclical and
      irregular components, and further illustrated by development of a classical Box
      Jenkins ARMA (autoregressive moving average) model for monthly ICU-patient
      hospital mortality rates recorded over 11 years. Multilevel (random-effects)
      models and principles of meta-analysis are outlined, and the review concludes
      with a brief consideration of important statistical aspects of clinical trials:
      sample size determination, interim analysis and "early stopping".

PMID- 17536992
TI  - Advancing intensive care research in Australia and New Zealand: development of
      the binational ANZIC Research Centre.
AB  - Over the past 12 years, the Australian and New Zealand Intensive Care Society
      (ANZICS) Clinical Trials Group and the broader intensive care community in
      Australia and New Zealand have established a track record for conducting high
      quality, investigator-initiated clinical research in critically ill patients.
      This is highlighted by the publication of the SAFE (Saline Albumin Fluid
      Evaluation) study in the New England Journal of Medicine and the MERIT (Medical
      Early Response Intervention and Therapy) study in the Lancet. Here, we discuss
      potential impediments to the further advancement of intensive care research in
      Australia and New Zealand, and suggest strategies to address them. We propose
      that there is a need to broaden the current research scope and develop more
      multifaceted research programs that address clinically important issues. We
      stress the need to also undertake phase II studies to assess safety,
      pharmacokinetics and biological plausibility of new and established therapies. In
      addition, we highlight limitations imposed by the relatively small regional
      population of Australia and New Zealand, and the need to develop international
      collaborations to allow trials requiring large sample sizes. We contend that the
      best chance of improving outcomes in many disease states requires studies to
      commence before patients enter the ICU, which will depend on collaboration with
      established and emerging craft groups, such as ambulance services, emergency
      medicine and anaesthesia. We also emphasise the need to study system factors
      affecting patient outcomes, as well as the translation of research findings into
      clinical practice. Finally, we describe the establishment and objectives of the
      Australian and New Zealand Intensive Care Research Centre (ANZIC-RC) and outline
      the Centre's current projects in the context of an integrated research framework.

PMID- 17536993
TI  - The effectiveness of implementation of the medical emergency team (MET) system
      and factors associated with use during the MERIT study.
AB  - OBJECTIVE: The potential of the medical emergency team (MET) system to reduce
      adverse events may depend on the effectiveness of its implementation. We aimed to
      evaluate the effectiveness of the implementation of the MET system during the
      MERIT (Medical Early Response, Intervention and Therapy) study and to determine
      factors associated with the level of MET system utilisation. METHODS: Surveys
      were conducted on the nursing staff from the general adult wards of all 12 MERIT
      study intervention hospitals after the 4-month implementation period and again
      after the 6-month study period. Hospital level variables were assessed for their
      correlation with MET utilisation. We measured awareness and understanding of the
      MET system, attendance at a MET education session, knowledge of the activation
      criteria, intention to call the MET, attitude to the MET system and the level of
      MET utilisation. RESULTS: Across the 12 intervention hospitals, a median of 85.6%
      (interquartile range, 81.3%-88.8%) of MET activations were not related to a
      cardiac arrest or death. This measure of MET system utilisation varied
      significantly across the 12 hospitals (P = 0.002), and was significantly
      associated with knowledge of the activation criteria (P = 0.048), understanding
      of the purpose of the MET system (P = 0.01), perceptions of the hospital's
      readiness for a change in the way care was provided (P = 0.004), and an overall
      positive attitude to the MET system (P = 0.003). CONCLUSIONS: Measures of the
      process of implementation of the MET system were significantly associated with
      the level of MET system utilisation.

PMID- 17536994
TI  - A pilot audit of the process of end-of-life decision-making in the intensive care
      unit.
AB  - BACKGROUND: Withdrawal of potentially life-prolonging treatments is a common
      procedure in most intensive care units. Until recently, quality improvement
      activities have been hampered by the absence of a clear sense of "best practice"
      in this complex area. OBJECTIVE: This pilot audit addresses the feasibility of
      developing an end-of-life (EOL) decision-making audit and quality improvement
      tool and applying it in the intensive care setting. METHODS: Between November
      2005 and April 2006, treatment was withdrawn from 47 patients in our ICU. Their
      charts were audited, and a structured interview was conducted with the
      intensivist who documented the decision. We defined treatment withdrawal as the
      cessation of mechanical ventilation and all other forms of life support in the
      anticipation of the patient's death. RESULTS: 55% of ICU deaths were the result
      of treatment withdrawal. Overwhelmingly, treatment failure or futility was the
      reason cited for withdrawal. There were no cases of conflict between the medical
      team and the patient's family. The level of confidence among intensivists about
      EOL decision-making was high. Consultation with ICU colleagues was rated as the
      most helpful factor in decisionmaking. Intensivists wished for earlier and more
      active support from the admitting medical officers in decisionmaking. Strong
      support for advance planning and for audit of EOL decision-making was
      highlighted. CONCLUSIONS: A current ICU quality improvement review lists EOL
      management as a possible audit item (Curtis et al. Crit Care Med 2006; 34: 211).
      Our study demonstrated the feasibility of developing a quality improvement tool
      for EOL decision-making and applying it in the intensive care setting. As
      evidence about the process of EOL decisionmaking accumulates, that process should
      become a component of quality assurance audit in intensive care.

PMID- 17536995
TI  - The ideal intensive care unit: open, closed or somewhere between?

PMID- 17536996
TI  - History of mouth-to-mouth ventilation. Part 3: the 19th to mid-20th centuries and
      "rediscovery".
AB  - The start of the 19th century saw the enthusiasm of the previous one for mouth-to
      mouth ventilation (MMV) dissipated. To inflate the lungs of the asphyxiated, the
      Royal Humane Society in the United Kingdom had recommended bellows since 1782.
      Principal determinants for change were aesthetic distaste for mouth-to-mouth
      contact and the perceived danger of using expired air, although MMV survived in
      the practice of some midwives. Following the 1826-9 investigations of Jean
      Jacques Leroy d'Etiolles then Francois Magendie, all positive pressure
      ventilation methods were generally abandoned, after 1829 in France, and 1832 in
      the UK; but not chest compressions. During the next quarter century, rescuers
      lost understanding of the primary need for "artificial respiration", apart from
      researchers such as John Snow and John Erichsen, until Marshall Hall's "Ready
      Method" heralded the second half-century's various methods of negative pressure
      ventilation. Some of those methods continued in use until the 1940s. Sporadic
      anecdotal cases of MMV rescues were documented throughout. In the 20th century,
      inadequate mechanical inhalators were also tried from 1908, while obstetricians
      devised indirect methods of expired air ventilation (EAV). Anaesthetists in the
      1940s, such as Ralph Waters, Robert Dripps, and the pair, Robert Macintosh and
      William Mushin, described the usefulness of MMV, and James Elam was "re
      discovering" it. Following World War II, "Cold War" concerns stimulated research
      at the Edgewood Medical Laboratories in Maryland in the United States into the
      possibilities of MMV, and Elam et al confirmed and expanded on brief experiments
      at Oxford (United Kingdom) on the efficacy of mouth-to-tube EAV. Studies, 1957-9,
      by Archer Gordon, Elam and especially Peter Safar resulted in the resolution of
      previous airway problems, established the primacy of MMV, and incorporated it
      into an integrated system for basic cardiopulmonary resuscitation. Ready adoption
      of MMV in the US was followed by worldwide spread, especially after endorsement
      from the 1962 international symposium at Stavanger in Norway. However, already
      there were occasional rumblings of reluctance to perform MMV. In this article, I
      consider MMV also in the context of other ventilatory modes for resuscitation.

PMID- 17536997
TI  - Happy Easter!

PMID- 17536998
TI  - Role of the placenta in fetal programming: underlying mechanisms and potential
      interventional approaches.
AB  - Adverse influences during fetal life alter the structure and function of distinct
      cells, organ systems or homoeostatic pathways, thereby 'programming' the
      individual for an increased risk of developing cardiovascular disease and
      diabetes in adult life. Fetal programming can be caused by a number of different
      perturbations in the maternal compartment, such as altered maternal nutrition and
      reduced utero-placental blood flow; however, the underlying mechanisms remain to
      be fully established. Perturbations in the maternal environment must be
      transmitted across the placenta in order to affect the fetus. Here, we review
      recent insights into how the placenta responds to changes in the maternal
      environment and discuss possible mechanisms by which the placenta mediates fetal
      programming. In IUGR (intrauterine growth restriction) pregnancies, the increased
      placental vascular resistance subjects the fetal heart to increased work load,
      representing a possible direct link between altered placental structure and fetal
      programming of cardiovascular disease. A decreased activity of placental 11beta
      HSD-2 (type 2 isoform of 11beta-hydroxysteroid dehydrogenase) activity can
      increase fetal exposure to maternal cortisol, which programmes the fetus for
      later hypertension and metabolic disease. The placenta appears to function as a
      nutrient sensor regulating nutrient transport according to the ability of the
      maternal supply line to deliver nutrients. By directly regulating fetal nutrient
      supply and fetal growth, the placenta plays a central role in fetal programming.
      Furthermore, perturbations in the maternal compartment may affect the methylation
      status of placental genes and increase placental oxidative/nitrative stress,
      resulting in changes in placental function. Intervention strategies targeting the
      placenta in order to prevent or alleviate altered fetal growth and/or fetal
      programming include altering placental growth and nutrient transport by
      maternally administered IGFs (insulin-like growth factors) and altering maternal
      levels of methyl donors.

PMID- 17536999
TI  - Arterial adaptations to chronic changes in haemodynamic function: coupling
      vasomotor tone to structural remodelling.
AB  - Healthy mature arteries are usually extremely quiescent tissues with cell
      proliferation rates much below 1%/day and with extracellular matrix constituents
      exhibiting half-lives of years to decades. However, chronic physiological or
      pathological changes in haemodynamic function elicit arterial remodelling
      processes that may involve substantial tissue synthesis, degradation or turnover.
      Although these remodelling processes accommodate changing demands placed upon the
      cardiovascular system by physiological adaptations, they can compromise further
      perfusion in the context of arterial occlusive disease and they entrench
      hypertension and may exacerbate its progression. Recent findings indicate that
      some of the most important such remodelling responses involve the integrated
      effects of persistently altered vascular tone that feed into restructuring
      responses, with common signalling pathways frequently interacting in the control
      of both phases of the response. Current efforts to define these signals and their
      targets may provide new directions for therapeutic interventions to treat
      important vascular disorders.

PMID- 17537000
TI  - Maurocalcine interacts with the cardiac ryanodine receptor without inducing
      channel modification.
AB  - We have previously shown that MCa (maurocalcine), a toxin from the venom of the
      scorpion Maurus palmatus, binds to RyR1 (type 1 ryanodine receptor) and induces
      strong modifications of its gating behaviour. In the present study, we
      investigated the ability of MCa to bind to and modify the gating process of
      cardiac RyR2. By performing pull-down experiments we show that MCa interacts
      directly with RyR2 with an apparent affinity of 150 nM. By expressing different
      domains of RyR2 in vitro, we show that MCa binds to two domains of RyR2, which
      are homologous with those previously identified on RyR1. The effect of MCa
      binding to RyR2 was then evaluated by three different approaches: (i)
      [(3)H]ryanodine binding experiments, showing a very weak effect of MCa (up to 1
      muM), (ii) Ca(2+) release measurements from cardiac sarcoplasmic reticulum
      vesicles, showing that MCa up to 1 muM is unable to induce Ca(2+) release, and
      (iii) single-channel recordings, showing that MCa has no effect on the open
      probability or on the RyR2 channel conductance level. Long-lasting opening events
      of RyR2 were observed in the presence of MCa only when the ionic current
      direction was opposite to the physiological direction, i.e. from the cytoplasmic
      face of RyR2 to its luminal face. Therefore, despite the conserved MCa binding
      ability of RyR1 and RyR2, functional studies show that, in contrast with what is
      observed with RyR1, MCa does not affect the gating properties of RyR2. These
      results highlight a different role of the MCa-binding domains in the gating
      process of RyR1 and RyR2.

PMID- 17537001
TI  - Erythropoietin and ischemic conditioning--why two good things may be bad.

PMID- 17537002
TI  - End-of-life decisions, quality of life and the newborn.

PMID- 17537003
TI  - Blue light, green light, turquoise light: do we need to change our devices to
      treat our jaundiced preterm infants?

PMID- 17537004
TI  - General vaccination of children against varicella?--Yes!

PMID- 17537005
TI  - Neuro-developmental effects of breastfeeding.

PMID- 17537006
TI  - Take a breath--but do not add oxygen (if not needed).

PMID- 17537007
TI  - Oxygen as a neonatal health hazard: call for detente in clinical practice.
AB  - Education in oxygenation and in how oxygen is given to newborns needs to
      increase. Treatment with oxygen should no longer be considered proverbial and
      customary, regardless of our 'past experience' or consensus recommendations in
      clinical guidelines, since oxygen may lead to acute or chronic health effects.
      CONCLUSION: Inappropriate oxygen use is a neonatal health hazard associated with
      aging, DNA damage and cancer, retinopathy of prematurity, injury to the
      developing brain, infection and others. Neonatal exposure to pure O2, even if
      brief, or to pulse oximetry >95% when breathing supplemental O2 must be avoided
      as much as possible.

PMID- 17537008
TI  - Kostmann syndrome or infantile genetic agranulocytosis, part two: Understanding
      the underlying genetic defects in severe congenital neutropenia.
AB  - Congenital neutropenia in man was first reported 50 years ago by the Swedish
      paediatrician Rolf Kostmann. He coined the term 'infantile genetic
      agranulocytosis' for this condition, which is now known as Kostmann syndrome.
      Recent studies have revealed mutations in ELA-2, encoding the neutrophil granule
      protease, neutrophil elastase, in autosomal dominant neutropenia, and mutations
      in HAX-1, encoding an anti-apoptotic protein, in autosomal recessive neutropenia.
      CONCLUSION: Future studies should aim to clarify the mechanisms underlying the
      evolution of secondary malignancies in these patients.

PMID- 17537009
TI  - End-of-life decision making in neonates and infants: comparison of The
      Netherlands and Belgium (Flanders).
AB  - AIM: We compared the results of two recent studies on end-of-life decisions
      (ELDs) for neonates and infants in Belgium (Flanders) and The Netherlands.
      METHODS: Questionnaires were sent to physicians who reported the death of a child
      under the age of 1 (Belgium: n = 292, response 87%; Netherlands: n = 249,
      response 84%). The questionnaires included structured questions about whether
      death had been preceded by ELDs, and about the decision-making process. RESULTS:
      In both countries, in about 25% of all deaths a life-sustaining treatment was
      withheld, and in about 40% pain or other symptoms were alleviated taking into
      account that death might be hastened. In Belgium, a life-sustaining treatment was
      less often withdrawn than in The Netherlands (32% vs. 50%, respectively). Drugs
      were administered with the explicit intention of hastening death in similar
      percentages of all deaths (Belgium: 7%; Netherlands: 9%). Dutch physicians more
      often than Belgian physicians discussed ELDs with parents (96% vs. 81%,
      respectively), and with colleague physicians (94% vs. 80%, respectively).
      CONCLUSIONS: End-of-life decision making in severely ill neonates seems to be
      rather similar in Belgium and The Netherlands. Differences are that Dutch
      physicians more often withdraw life-sustaining treatment. Furthermore, parents
      and colleague physicians are more often involved in the decision making in The
      Netherlands.

PMID- 17537010
TI  - Physicians' use of guidelines and attitudes to withholding and withdrawing
      treatment for extremely premature neonates in Norway.
AB  - OBJECTIVES: To examine if explicit written guidelines for withholding and
      withdrawing treatment for extremely premature infants exist and are used in
      obstetric and paediatric units in Norway, and to explore changes in attitudes and
      which factors are considered important when making decisions regarding life
      support. METHODS: Cross-sectional postal survey addressed to the medical
      directors of all the 46 obstetric and the 28 paediatric units in Norway. RESULTS:
      The response rate was 84%. Half the units had guidelines for withholding and one
      quarter for withdrawing life support. Most of them were non-written informal
      guidelines. The most important factors for withholding treatment were gestational
      age and vitality while risk of severe disability and future quality of life were
      the major concerns for withdrawing treatment. The mean reported gestational age
      threshold for resuscitating infants decreased from 23.6 weeks (SD +/- 0.6) in a
      study from 1998 to 23.0 weeks (SD +/- 0.8) in 2005 (p = 0.001). Physicians did
      not perceive this change in threshold, but 1/3 felt that decisions regarding
      provision of life support had become more difficult. Almost half of the
      responding physicians agreed with the statement that Norway is too liberal in its
      provision of life support to extremely premature infants. CONCLUSION: The
      criteria for whom to provide life support or not are imprecise and may be subject
      to unperceived changes. Explicit local guidelines for the decision-making process
      may secure legitimacy and fair treatment options.

PMID- 17537011
TI  - Therapeutic effect of turquoise versus blue light with equal irradiance in
      preterm infants with jaundice.
AB  - AIM: To compare the efficiency of turquoise light with that of TL52 blue in
      treatment of preterm infants with jaundice at the same level of body irradiance.
      METHODS: Infants with gestational age 28-37 weeks and non-haemolytic
      hyperbilirubinemia were treated for 24 h with either turquoise light (OSRAM
      L18W/860 fluorescent lamps) or blue light (Philips TL20W/52 fluorescent lamps).
      The concentrations of serum total bilirubin and bilirubin isomers were measured
      by the Vitros routine method and by HPLC, respectively. RESULTS: The decrease in
      serum concentrations of total bilirubin, total bilirubin isomers and the toxic
      Z,Z-bilirubin was greatest for infants treated with turquoise light. Further, the
      increase in Z,E-bilirubin was smaller and there was a trend towards a higher rise
      in E,Z-bilirubin. CONCLUSIONS: Turquoise light has a greater bilirubin reducing
      effect than TL52 blue light with equal irradiance, expressed both by serum total
      bilirubin, total bilirubin isomers and Z,Z-bilirubin, i.e. the turquoise spectral
      range is more efficient than the blue. This is in accordance with deeper
      penetration into the skin, lower production of the Z,E-bilirubin and greater
      production of E,Z-bilirubin and lumirubin, in infants under turquoise light. This
      suggests, given equal irradiances, that light in the turquoise spectral range is
      preferable to the TL52 blue in treatment of newborn jaundiced infants.

PMID- 17537012
TI  - Attention behaviour and hyperactivity at age 4 and duration of breast-feeding.
AB  - AIM: The relation of longer duration of breast-feeding to cognitive development
      was been demonstrated in several previous studies, however its potential impact
      on behaviour is unknown. We assess which behavioural areas (executive function,
      social competence, attention behaviour and hyperactivity) are related to long
      term breast-feeding in young children. METHODS: Two prospective population-based
      birth cohorts, one from the island of Menorca (N = 421) and the second from
      Ribera d'Ebre county (N = 79) in Spain were followed up at the age of 4 years
      during a two year period (2001-2003). Children were assessed by three
      psychologists and their respective teachers for neuropsychological functions
      (McCarthy test), attention-hyperactivity behaviours (Attention-Deficit
      Hyperactivity Disorder Criteria of DSM-IV) and social behaviour (California
      Preschool Social Competence Scale). RESULTS: Long-term breast-feeding was
      associated with executive function scores (an increase of 4.9 points after breast
      feeding >20 weeks), and the improvement of social competence scores (relative
      risk for being in the poorest 20%, RR = 0.57; 0.52-0.66, after >12 weeks) and
      attention-deficit hyperactivity symptom scores (RR = 0.56; 0.37-0.85, after >12
      weeks). All three outcomes remained significant when included as covariates in
      the regression models. CONCLUSION: Long-term breast-feeding was found to be
      associated with fewer attention and hyperactivity symptoms and an improvement in
      related behavioural areas (neuropsychological and socio-behavioural outcomes).

PMID- 17537013
TI  - Attitudes and knowledge on breastfeeding among paediatricians, family physicians,
      and gynaecologists in Israel.
AB  - OBJECTIVES: Many women in Western countries fail to breastfeed long enough. The
      aim of this study was to examine the attitudes and knowledge of Israeli family
      physicians (FPs), gynaecologists and paediatricians towards breastfeeding. DESIGN
      AND PARTICIPANTS: A questionnaire examined Physicians' attitudes towards
      breastfeeding and their role in encouraging it, their sources of information and
      adequacy of knowledge. RESULTS: Four hundred and seventy-eight physicians
      responded to the survey: 123 FPs, 134 gynaecologists and 221 paediatricians.
      Ninety to -hundred per cent of physicians agreed that breastfeeding is the best
      feeding method for infants and agree that physicians should encourage it. Less
      than 20% of physicians discuss breastfeeding with pregnant women, and less than
      30% discuss it with women 3 months or more postnatally. On average, physicians
      correctly answered 3.5 +/- 1.7 out of seven questions examining knowledge.
      Physicians state their main sources of information as their own experience and
      reading. One hundred and ninety physicians specified how they encourage
      breastfeeding--of those, 75.3% speak only of the advantages of breastfeeding.
      CONCLUSION: Physicians have a positive disposition towards breastfeeding but
      their knowledge is somewhat low. It seems awareness is lacking to the importance
      of continuous support and practical guidance beginning before birth and
      continuing until 3 months or more postnatal.

PMID- 17537014
TI  - Infant feeding patterns and midlife erythrocyte sedimentation rate.
AB  - AIM: To assess the erythrocyte sedimentation rate (ESR), and other coronary heart
      disease (CHD) risk factors in adults who were either breast- or bottle-fed in
      early infancy. METHODS: Subjects were 3614 men and women born 1914-1935.
      Information on infant feeding patterns was gathered from original midwife's birth
      records. Adult ESR, triglycerides, total cholesterol, blood pressure, fasting
      glucose, weight and height were measured. RESULTS: The number of subjects bottle
      fed in early infancy was 186 (5.2%). The geometric mean of ESR was 15.9% (95% CI
      1.8%-31.8%) higher in those who were bottle-fed compared with those breastfed, p
      = 0.026, when adjusting for age and gender. Those who had been breastfed in early
      infancy had on average 2.9% higher BMI in adulthood (p = 0.012). The hazard ratio
      for event of CHD for bottle-fed persons versus breastfed was 1.18 (95% CI 0.88
      1.57), adjusting for potential confounding factors. CONCLUSIONS: Higher adult
      ESR, a moderate risk factor for CHD, among those bottle-fed compared to those
      breastfed in early infancy might indicate a long term anti-inflammatory influence
      of breast milk.

PMID- 17537015
TI  - Impedance index or standard anthropometric measurements, which is the better
      variable for predicting fat-free mass in sick children?
AB  - AIM: To compare the predictive value of impedance index (ZI, height2/impedance)
      with anthropometric measurements for estimating fat-free mass (FFM). METHODS: FFM
      of 120 white paediatric children (46 males, 74 females), aged 2.5-18 years was
      measured by using dual energy X-ray absorptiometry. Weight, height, mid-upper arm
      circumference (MUAC), skinfold thickness (biceps, triceps, subscapular and
      suprailiac) and bioelectrical impedance were also obtained. Stepwise multiple
      regression analysis and residual plots were performed to determine the most
      significant variables to predict FFM. RESULTS: The single best predictor of FFM
      was ZI, which explained 96.2% of the variance in FFM (r = 0.981, SEE = 2.15 kg).
      Addition of weight to the model containing ZI increased the explained variance of
      FFM to 96.6% (r = 0.983, SEE = 2.03 kg). BMI and MUAC were the poorest predictors
      of FFM: r = 0.422, SEE = 10.2 kg and r = 0.621, SEE = 8.93 kg, respectively.
      CONCLUSION: Impedance index is a more significant single predictor of FFM than
      other anthropometric measurements. The predictive accuracy of bioelectrical
      impedance analysis-based prediction equations for FFM was improved by addition of
      weight.

PMID- 17537016
TI  - Bone mass accretion rates in pre- and early-pubertal South African black and
      white children in relation to habitual physical activity and dietary calcium
      intakes.
AB  - AIM: To examine bone mass changes in 321 black and white South African children
      in relation to habitual physical activity (PA) levels and calcium intakes.
      METHODS: Children underwent two bone mass scans at ages nine and 10 years using
      dual X-Ray absorptiometry. PA levels and calcium intakes were assessed using
      questionnaires. Data were analyzed by regressing change in bone mineral content
      (BMC) and bone area (BA) from age nine to 10, against BA (for BMC), height and
      body weight. The residuals were saved and called residualized BMCGAIN and BAGAIN.
      Residualized values provide good indication of weight, height and BA-matched
      accumulation rates. RESULTS: White children had significantly higher PA levels
      and calcium intakes than black children. Most active white males had
      significantly higher residualized BMCGAIN and BAGAIN at the whole body, hip and
      spine but not at the radius, than those who were less active. Most active white
      females had significantly higher residualized BAGAIN at all sites except the
      radius than less-active girls. No such effects were seen in black children. There
      was no interactive effect on residualized BMCGAIN for calcium intake and PA
      (except at the spine in white girls). CONCLUSION: Bone mass and area gain is
      accentuated in pre- and early-pubertal children with highest levels of habitual
      physical activity. Limited evidence of an effect of dietary calcium intakes on
      BMC was found.

PMID- 17537017
TI  - Sustained metabolic control and low rates of severe hypoglycaemic episodes in
      preschool diabetic children treated with continuous subcutaneous insulin
      infusion.
AB  - AIM: To evaluate the safety and efficacy of continuous subcutaneous insulin
      infusion (CSII) in children under 7 years of age. METHODS: One hundred and ten
      children, aged 0.9-7 years, who had received CSII therapy for at least 6 months,
      were studied for 237 patient-years by a retrospective chart review. Charts were
      reviewed for glycosylated hemoglobin (HbA1c), severe hypoglycaemia (SH),
      ketoacidosis (DKA), height, weight and insulin requirement. In 69 cases (children
      aged 1.6-7 years) CSII was administered after at least 3 months of insulin
      therapy with pens. In this group, data from the year from before CSII
      administration were compared with values recorded during 1 year of CSII
      treatment. RESULTS: Mean HbA1c decreased from 7.8 +/- 0.9 before CSII to 7.5 +/-
      1.0 after 6 and 12 months of pump therapy (p = 0.04). In the whole group, the
      mean HbA1c after 6 months of CSII was 7.5 +/- 1.0 and remained unchanged for up
      to 4 years of follow-up. Some episodes of SH--4.2 per 100 patient-years, and DKA-
      5.7 per 100 patient-years were recorded. No increase in BMI z-score occurred.
      CONCLUSIONS: In the youngest children, CSII therapy lowers HbA1c values and
      provides sustained metabolic control without increases in hypoglycaemia or
      ketoacidosis episodes.

PMID- 17537018
TI  - Screening Copenhagen school children at risk of type 2 diabetes mellitus using
      random capillary blood glucose.
AB  - AIM: To screen adolescents at risk of type 2 diabetes mellitus (T2DM) using
      random capillary blood glucose (RCBG). METHODS: Ninth grade pupils who were
      overweight and/or had a family history of T2DM were offered to have RCBG measured
      and were referred for further investigation if the value was > or = 7.8 mmol/L.
      RESULTS: Two thousand four hundred and eleven pupils were examined, 19% were
      overweight, 4% being obese. 589 met inclusion criteria and 384 participated.
      Ethnic minorities and pupils in low socio-economic school-areas (SESA) were
      significantly more overweight than ethnic Danes and pupils in high SESA. Compared
      to ethnic Danish pupils, the relative risk of having a positive parent history of
      T2DM was increased five-fold for ethnic Turkish and Arab pupils and 13-fold for
      ethnic Pakistani pupils. One pupil had a diagnosed T2DM. Two had elevated RCBG
      values. One of these had an undiagnosed T2DM. CONCLUSION: Our study shows a high
      prevalence of overweight adolescents in Copenhagen, especially in school areas
      with low socio-economic standard and in pupils with Turkish, Pakistani and Arab
      ethnicity. Only three out of the 10 pupils with the highest risk participated.
      New strategies to reach and motivate risk groups to follow health recommendations
      and new methods of screening should be developed.

PMID- 17537019
TI  - Mental health in adolescents with chronic physical illness versus controls in
      Northern Russia.
AB  - AIM: To study the behaviour/emotional problems and depression in adolescents with
      and without physical illnesses; to compare the same psychological parameters in
      adolescents with different disorders. METHODS: The sample consisted of 148
      adolescents aged 13-16 years with one of the following physical chronic
      conditions: diabetes (n = 55), asthma (n = 59), or epilepsy (n = 59). Comparative
      data were obtained from a group of 301 schoolchildren. Test batteries (Child
      Behaviour Check-List, Youth Self Report, Beck Depression Inventory, socio
      economic status questions) were individually completed by adolescents and their
      mothers. RESULTS: Overall adolescents with physical illness had more
      behaviour/emotional problems and were more depressed compared to controls
      although results varied according to the informants and the disease severity. Two
      risk groups were revealed: girls with asthma and boys with epilepsy. CONCLUSION:
      Our results suggest that mental health in adolescents with chronic physical
      illnesses is poorer than in controls and their mental health state is very much
      associated with the disease severity. The findings of the study can help to
      develop disease targeted and comprehensive interventions in outpatient clinics of
      Northern Russia in order to reduce behaviour and mood disorders in adolescents
      with chronic physical illnesses and therefore to smooth the transition through
      their teenage years.

PMID- 17537020
TI  - Screening for postnatal depression in Swedish child health care.
AB  - AIM: To investigate how postnatal depressive mood was identified by child health
      nurses and which factors were associated with the implementation of screening for
      postnatal depression and with offering supportive listening visits. METHODS: A
      random sample of all 2580 nurses in child health services in Sweden, 499 nurses,
      were asked to complete a postal questionnaire. A response rate of 70% was
      achieved. RESULTS: Half of the nurses in the study used the Edinburgh Postnatal
      Depression Scale (EPDS) and at least another 7% were going to begin. Having the
      appropriate training, access to regular supervision and pathways to care were
      essential, and increased the likelihood of using the EPDS. The odds of using the
      EPDS were six times greater for nurses with access to supervision as compared
      with nurses without supervision. Most of the nurses who used the EPDS included a
      follow-up interview on the same occasion as the mother completed the scale, and
      four out of five nurses allowed extra time for the EPDS. More than half of these
      allowed half an hour or more. The significance of factors associated with the
      implementation of routine screening is discussed. CONCLUSION: Training,
      supervision and pathways to care were essential for the implementation of routine
      screening with the EPDS.

PMID- 17537021
TI  - Genotype and phenotype in patients with Prader-Willi syndrome in Taiwan.
AB  - AIM: Several different genetic defects have been found to result in the
      characteristic phenotypic expression of Prader-Willi syndrome (PWS). METHODS: We
      performed a retrospective analysis of 67 cases of molecularly confirmed PWS
      diagnosed from January 1980 through July 2006 in five medical centres in Taiwan.
      Clinical manifestations were compared between patients with deletion and those
      with maternal uniparental disomy (UPD). RESULTS: Deletion was present in 56
      (84%), UPD in 10 (15%), and a probable imprinting centre deletion or imprinting
      defect in 1 (1%). PWS with deletion was more likely than that with UPD to be
      characterized by hypogonadism (p < 0.001), small hands and feet (p < 0.001), and
      hypopigmentation (p < 0.002). Both maternal (p = 0.015) and paternal age (p =
      0.021) were higher in the UPD group. No other clinical features differed
      significantly different between the two groups. CONCLUSION: In contrast to most
      Western populations with a higher incidence of UPD, this study of PWS in Taiwan
      shows a higher incidence of deletion. There may be subtle phenotypic differences
      between the UPD and deletion genotypes, but its not clear that these are
      important clinically.

PMID- 17537022
TI  - Outcome of pulmonary and aortic stenosis in Williams-Beuren syndrome in an Asian
      cohort.
AB  - AIMS: To define the cardiovascular anomalies and the long-term outcomes in an
      Asian cohort with Williams-Beuren syndrome (WBS). METHODS: Data were retrieved
      from a retrospective chart review of patients who had a definitive diagnosis of
      WBS by fluorescence in situ hybridization between 1995 and 2005. All patients
      underwent echocardiography every 3-9 months. Ten patients underwent cardiac
      catheterization. RESULTS: Twenty-one patients with a total follow-up of 134
      patient-years (median: 72 months) were enrolled. Characteristic dysmorphic facial
      features were noted in 19 patients (n = 19, 90%). All except one had associated
      cardiac anomalies, accounting for 0.3% (20/6640) of the patients with congenital
      heart disease. The spectrum of cardiac anomalies included supravalvular aortic
      stenosis (SVAS) (n = 15, 71%), peripheral pulmonary stenosis (PPS) (n = 12, 57%),
      pulmonary valve stenosis (PS) (n = 10, 47%), mitral valve prolapse (MVP) (n = 9,
      43%), coarcation of the aorta (n = 4, 19%), ventricular septal defect (n = 2,
      10%) and atrial septal defect (n = 1, 5%). Concurrent SVAS and PS/PPS were found
      in 14 (70%) patients. Only one patient required balloon dilation of PS, which
      improved. Regression of the stenoses occurred with a probability of 31, 90 and
      71% at the age of 10 years for SAVS, PS and PPS, respectively. CONCLUSIONS: Among
      our WBS patients, SVAS, PPS and PS were common, and were associated with
      probability of spontaneous regression, especially of right-sided lesions.

PMID- 17537023
TI  - Effect of formula thickened with reduced concentration of locust bean gum on
      gastroesophageal reflux.
AB  - AIM: Previous studies showed that HL-350, a formula thickened with a reduced
      concentration of locust bean gum, decreased frequent regurgitation in 4-month old
      infants with reflux. In this study, we investigated the effect of HL-350 in
      younger infants. METHODS: We studied 20 infants less than 2 months old who had
      three or more episodes of regurgitation or vomiting per day. Ten infants (group
      A) were fed with HL-350 for the first week, and with control milk, HL-00, for the
      following week. The other 10 infants (group B) were fed in reverse order. Mothers
      recorded number of regurgitation episodes, feeding volume and time and number of
      bowel movements. To evaluate gastric emptying we measured antral cross sectional
      areas ultrasonographically at various time points after feeding. RESULTS: The
      median number of regurgitation episodes decreased significantly with feeding of
      HL-350 (2.3/day) compared to feeding with control milk (5.2/day) (p = 0.00048).
      No significant difference was evident in feeding volume and time, body weight
      gain, or gastric emptying rate between HL-350 and control milk. CONCLUSION: HL
      350 decreased the number of regurgitation episodes without affecting gastric
      emptying delay in very young infants with recurrent vomiting.

PMID- 17537024
TI  - Reduction in the number of orchidopexies for cryptorchidism after recognition of
      acquired undescended testis and implementation of expectative policy.
AB  - BACKGROUND: Since the mid-1990s, acquired undescended testis has gradually been
      recognised as a separate entity for which the efficacy of prepubertal surgery has
      not been univocally been demonstrated. Therefore, in our hospital, orchidopexy
      was no longer routinely performed for acquired undescended testis. AIM: To
      investigate the effect of expectative policy in our hospital on the number of
      orchidopexies. METHODS: Two 5-year periods were compared. Period A (1991-1995),
      in which undescended testis was treated surgically, and period B (2000-2004), in
      which prepubertal orchidopexy in our hospital was no longer performed for
      acquired undescended testis. In addition, a comparison was made between the
      percentage reduction in hospital and national figures. RESULTS: In period B, the
      number of orchidopexies in our hospital was reduced by 61.8% (from 387 to 148),
      mainly in the age group >6 years. Nationally, during the same period, the number
      of orchidopexies decreased only by 2.4% (from 18 024 to 17 591). CONCLUSION: The
      results of this study confirm that recognition of acquired undescended testis is
      crucial for reducing the high number of (late) orchidopexies.

PMID- 17537025
TI  - Trends in hospitalization for childhood asthma in Finland in 1996-2004.
AB  - AIM: To discuss trends based on data on all asthma-related admissions of children
      under 15 years of age. METHODS: retrospective analysis of records of the Finnish
      National Research and Development Centre for Welfare and Health in 1996-2004. The
      analysis was stratified for age. RESULTS: Out of the total of 23,715 such
      admissions, 66.8% involved boys. The number of all admissions for boys aged 0
      under 3 years declined by 42.7% (relative to the child population) between 1996
      and 2004, that for boys aged 3-under 5 years by 55.1% and that for boys aged 5
      under 15 years by 59.0%, the figures for the corresponding age groups of girls
      being 53.0, 48.7 and 66.1%, respectively. The overall rate of first admissions
      for asthma among children (relative to population) declined by 36.8% during that
      period. CONCLUSIONS. The hospitalization of children for asthma has declined in
      Finland in recent times in all age and both sex groups. This favourable
      development coincides with the systematically programmed national shift into
      effective anti-inflammatory therapy in the paediatric age groups.

PMID- 17537026
TI  - Decrease in childhood asthma admissions in Athens, Greece from 2001 to 2005.

PMID- 17537027
TI  - Case 1: An infant with water intoxication.

PMID- 17537028
TI  - Case 2: An under-recognized cause of cyanosis in young children.

PMID- 17537029
TI  - Nine cases of childhood adrenal tumour presenting with hypertension and a review
      of the literature.
AB  - AIM: To describe the clinical features, treatment and outcome of children adrenal
      tumors presenting with hypertension. METHODS: The records of nine children under
      16 years of age with adrenal tumours presenting with hypertension were analysed.
      Details were recorded for family history, clinical presentation, biochemistry,
      imaging, histology, treatment and outcome. RESULTS: Abdominal mass was palpable
      only in one patient at diagnosis. Besides hypertension-associated symptoms,
      Cushing's syndrome was the common presentation form (n = 4). Abdominal computed
      topography showed adrenal mass in all patients. Tumours were completely resected
      for each patient. The median tumour weight was 73 g (11-530 g) and the size
      ranged from 1.5 x 1.5 to 12 x 14 cm2. Pheochromocytoma (n = 2), adrenocortical
      adenoma (n = 3), adrenocortical carcinoma (n = 1), neuroblastoma (n = 2) and
      ganglioneuromas (n = 1) were found. In one case, adrenal pheochromocytoma first
      occurred and non-functioning islet cell tumour successively occurred at pancreas.
      A better status is common at a median follow-up time of 3.5 years. CONCLUSIONS:
      Childhood adrenal tumours presented with hypertension showed an atypical course,
      variable presentation. We report a unique case of adrenal pheochromocytoma
      followed by the occurrence of non-functioning islet cell tumour. Reversal of
      hypertension by surgery is crucial. Imaging techniques are important to detect
      adrenal tumours.

PMID- 17537030
TI  - C. Cori (1896-1984), G. Cori (1896-1957) and B. Houssay (1887-1971) Nobel Prize
      in 1947 for discoveries of glycogen metabolism with relevant and irrelevant
      clinical implications.

PMID- 17537031
TI  - Methylene blue irrigation-treatment of renal fungal balls causing acute renal
      failure in a preterm infant.

PMID- 17537037
TI  - A potential predictive marker for response to interferon in malignant melanoma.
AB  - The methylthioadenosine phosphorylase (mtap) gene is localized on chromosome
      9p21, a chromosomal region often affected by deletion in several kinds of
      malignant tumors. Studies on malignant melanoma have revealed loss of MTAP
      expression in vitro and in vivo; however, loss of MTAP expression is mainly
      regulated by promoter hypermethylation. Loss of MTAP was shown to have an effect
      on tumor invasion and metastasis. In a recent study, MTAP not only had a role as
      tumor suppressor but was also implicated in lack of therapeutic response of
      patients with recurrent malignant melanoma. There is evidence that loss of MTAP
      results in an inhibition of STAT signaling pathways regulated by interferon. This
      in turn leads to ineffectiveness of interferon therapy. Determination of the MTAP
      status in the primary tumor could, therefore, potentially lead to a selection of
      patients who benefit from interferon treatment.

PMID- 17537038
TI  - Therapeutic options for digital ulcers in patients with systemic sclerosis.
AB  - Digital ulcers (DU) affect up to half of all patients with systemic sclerosis at
      some point during their disease. These lesions are extremely painful, heal
      slowly, and lead to substantial disability. DU arise from recurrent ischemic
      injury and microtrauma. Treatments for DU include non-pharmacologic modalities
      such as avoiding cold,stress,and trauma,as well as smoking cessation. Possible
      pharmacologic therapies for the prevention of DU include vasodilating agents to
      treat Raynaud phenomenon, statins, and oral agents used in the treatment of
      pulmonary hypertension (endothelin receptor antagonists, phosphodiesterase-5
      inhibitors). The treatment of existing DU includes hydrocolloid occlusion, wound
      care, pain control, antibiotics, and the use of vasodilating medications.
      Intravenous or subcutaneous prostacyclins and digital or cervical sympathectomy
      should be considered for severe cases.

PMID- 17537039
TI  - Current state of vitiligo therapy--evidence-based analysis of the literature.
AB  - Vitiligo is a skin disease with a worldwide prevalence ranging from 0.5% to 4%.
      Conservative therapies include photochemotherapy, phototherapy with UVB radiation
      (broadband UVB 290-320 nm, narrow band UVB 311 nm), systemic steroids and
      pseudocatalase. Modern therapeutic options include treatment with topical
      immunomodulators (tacrolimus, pimecrolimus), analogues of vitamin D3, excimer
      laser and surgery/transplantation. Our analysis compares these therapies for
      vitiligo and the evidence levels supporting their effectiveness. CONCLUSIONS: The
      face and neck respond best to all therapeutic approaches, while the acral areas
      are least responsive. For generalized vitiligo, phototherapy with UVB radiation
      is most effective with the fewest side effects; PUVA is the second best
      choice.Topical corticosteroids are the preferred drugs for localized vitiligo.
      They may be replaced by topical immunomodulators which display comparable
      effectiveness and fewer side effects. The effectiveness of vitamin D analogues is
      controversial with limited data. Surgical therapy can be very successful, but
      requires an experienced surgeon and is very demanding of time and facilities,
      thus limiting its widespread use. L-phenylalanine therapy appears effective on
      the face but enjoys neither widespread use nor extensive data support. No single
      therapy for vitiligo can be regarded as the most effective as the success of each
      treatment modality depends on the type and location of vitiligo.

PMID- 17537040
TI  - Cryosurgical treatment of lentigo maligna.
AB  - BACKGROUND: Lentigo maligna (LM) is a common melanocytic malignancy which
      requires therapy because of the risk of progression to invasive lentigo maligna
      melanoma which a much worse prognosis. PATIENTS AND METHODS: 18 patients with
      clinical and histopathological diagnosis of LM were treated with cryosurgery. The
      patients were older Caucasians (mean age 59.5 years) and 11 were male. They were
      chosen for cryosurgery because the lesion posed a surgical challenge or the
      patient was not a good surgical candidate. They were treated with two freeze-thaw
      cycles of liquid nitrogen under local anesthesia in a single sitting. Lesions
      larger than 2 cm(2) were divided into smaller segments for freezing. RESULTS: The
      lesions resolved clinically in all cases, with no recurrence or metastasis
      detected during a mean follow-up of 75.5 months. Some patients developed
      hypopigmented scars. CONCLUSIONS: Cryosurgery with liquid nitrogen is an
      efficient, safe and in most cases aesthetically acceptable alternative method to
      treat LM.

PMID- 17537041
TI  - Health services research in dermatology--current update and perspectives.
AB  - BACKGROUND: An in-depth knowledge of the demands on health care resources and the
      quality of health care provision is of major importance for the future care of
      skin and allergy patients. We present a comprehensive summary of all available
      health care data and research activities in dermatology in Germany. METHODS: A
      standardized electronic literature search was performed using PUBMED as well as a
      manual search to identify activities in the field of health services research in
      dermatology. Furthermore, questionnaires were sent to 114 dermatology hospitals
      and to 52 health service research institutions in Germany. RESULTS: The overall
      return rate of the survey was 81%. Hints on projects were given by 30 hospitals
      and 5 institutions. Most of these projects were in the field of epidemiology,
      quality of life, economy and prevention. Finally, the search identified 101
      health services research projects in Germany. In addition, material gathered from
      internet and secondary citations from scientific journals produced a total of 216
      publications. Only few projects were found on the working conditions of
      physicians and other health care professionals, on the implementation of
      guidelines, on needs and use of dermatological services and on the quality of
      care. CONCLUSIONS: The findings demonstrate that there are substantial
      deficiencies in some important areas of health services research in dermatology.
      To provide efficient and qualified dermatological health care in Germany in the
      future, more research projects on the needs, demands and quality of health care
      are needed.

PMID- 17537042
TI  - Successful etanercept therapy in therapy refractory acrodermatitis continua
      suppurativa Hallopeau.
AB  - A 50-year-old patient presented with erythema, vesicles and pustules as well as
      interphalangeal joint pain. Acrodermatitis continua suppurativa Hallopeau was
      diagnosed. She was treated topically with glucocorticosteroids, calcitriol,
      calcipotriol, tacrolimus and bath-PUVA therapy without any clear benefit.
      Systemic acitretin 0.75 mg/kg daily led to improvement but complete resolution
      could never be achieved. Because of acitretin-induced mucosal side effects and
      hair loss, the dose was reduced to 20 mg/d alternating with 10 mg/d. The disease
      flared again. Additional therapy with etanercept 2 x 25 mg subcutaneously weekly
      was started. Within four weeks all symptoms resolved. The joint pain disappeared
      and the nail growth improved. After six months, etanercept therapy was
      discontinued. Two weeks later the first rebound of pustules occurred. Etanercept
      was restarted and the patient cleared rapidly. Etanercept therapy can be a useful
      therapeutic approach in refractory acrodermatitis continua suppurativa Hallopeau.

PMID- 17537043
TI  - Granulomatous jellyfish dermatitis.
AB  - The induction of a granulomatous inflammation by jellyfish toxins is rare. More
      typically, acute toxic and urticarial reactions are seen. An 11-year-old boy
      developed a striated urticarial erythema on the left cheek after contact with a
      gelatinous mass while swimming in the sea in Croatia. After initial erosion, a
      striated induration developed in the area of contact. Histological examination
      revealed a granulomatous inflammation with some eosinophils. While topical
      steroid-based antiinflammatory and antibacterial therapy over several weeks was
      not effective, topical therapy with tacrolimus 0.1% for two two-week treatment
      periods led to healing of the skin changes with a slight scar. There was no
      clinical recurrence after 5 month of follow-up.

PMID- 17537044
TI  - [The appraisal discussion as instrument of leadership and motivation].

PMID- 17537045
TI  - Proctology.

PMID- 17537046
TI  - [Asymptomatic scaly papules on the extremities and pinnae].

PMID- 17537047
TI  - [Finger stall technique skin graft for reconstruction of fingers after extensive
      excisions of acral lentiginous Melanomas].

PMID- 17537048
TI  - Streptococcal infections of the skin and mucous membranes.

PMID- 17537049
TI  - [Adolf Richard Fleischmann (1892 through 1968)--painter, scientific draftsman,
      moulager].

PMID- 17537050
TI  - [Letter on 'Recommendation: daily sun protection in the prevention of chronic UV
      induced skin damage'].

PMID- 17537051
TI  - [The Department Dermatology and Venereology at the University of Lehr and the
      Acute Care Hospital in Feldkirch, Vorarlberg are portrayed].

PMID- 17537052
TI  - [Adjuvant interferon therapy in malignant melanoma].

PMID- 17537053
TI  - Chimeric monkeys with human brains: a new bioethical black hole.

PMID- 17537054
TI  - Construction of skeletal myoblast-based polyurethane scaffolds for myocardial
      repair.
AB  - Intramyocardial transplantation of skeletal myoblasts augments postinfarction
      cardiac function. However, poor survival of injected cells limits this therapy.
      It is hypothesized that implantation of myoblast-based scaffolds would result in
      greater cell survival. Rat skeletal myoblasts were seeded on highly porous
      polyurethane (PU) scaffolds (7.5 x 7.5 x 2.0 mm). The effect of several scaffold
      pretreatments, initial cell densities, and culture periods was tested by DNA
      based cell count and viability assessment. Seeded PU scaffolds were implanted on
      infarcted hearts and immunohistology was performed 4 weeks later. Precoating with
      laminin allowed the most favorable cell attachment. An initial inoculation with 5
      x 10(6) cells followed by a 15-day culture period resulted in optimal myoblast
      proliferation. Four weeks after their implantation in rats, numerous myoblasts
      were found throughout the seeded patches although no sign of differentiation
      could be observed. This myoblast seeding technique on PU allows transfer of a
      large number of living myoblasts to a damaged myocardium.

PMID- 17537055
TI  - Numerical and in vitro investigations of pressure rise in a new hydrodynamic
      blood bearing.
AB  - The reliability and simplicity of rotor bearing are vital to the success of long
      term implantation of rotary blood pumps. This article describes both numerical
      and in vitro studies of the pressure rise in a 5-cm-diameter spiral groove
      bearing. Results show that the simplified analytical model overpredicts the
      pressure rise across the bearing while the results from a more comprehensive
      three-dimensional computational fluid dynamics (CFD) model agree well with the
      measurements. The discrepancy between the analytical model and the measurements
      is attributed to the exclusion of the fluid inertia effects in the analytical
      model. In addition, the assumption of linear pressure variations at the entrance
      of the groove and the ridge may have oversimplified the analysis. CFD results
      show that the pressure variation at the entrance of the groove and ridge is
      nonlinear. A correction factor taking into consideration the fluid inertia effect
      has been incorporated, and the modified analytical results agreed well with the
      measurement as well as that of the more comprehensive CFD model. The pressure
      generated is sufficient to lift the rotor, and this design provides the designer
      an alternative design for passive bearing.

PMID- 17537056
TI  - In vitro long-term fatigue endurance of the secondary "Cement Injection Stem" hip
      prosthesis.
AB  - A secondary cementation hip stem (Cement Injection Stem; Aesculap, Tuttlingen,
      Germany) was designed to reduce the risk of fat embolism, and achieve precise
      implant position and high-quality cement mantle. A validated long-term in vitro
      simulation was carried out that replicated 24 years of activity of a very
      demanding patient. Inducible and permanent micromotions were monitored. The
      cement mantle was sectioned and inspected for signs of fatigue damage. The stem
      cement interface was inspected for fretting. Results were compared against
      previously published results for a conventionally implanted stem with comparable
      design (Centrament; Aesculap) from which this project was derived. Comparable
      micromotions were found (slightly larger proximally, in correspondence to the
      precured centralizer). No sign of fretting was observed. All fatigue damage
      indicators were comparable or significantly better than those for the
      conventionally implanted stem. The few cement cracks found were mainly localized
      in proximity of a proximal drainage hole. It is foreseen that when this detail is
      optimized, long-term endurance will further improve.

PMID- 17537057
TI  - In vitro comparison of peracetic acid and bleach cleaning of polysulfone
      hemodialysis membranes.
AB  - Dialyzer reuse has been employed throughout the history of hemodialysis, but the
      practice remains controversial. Many studies have found changes in the beta(2)
      microglobulin clearance for reused dialyzers, but it is difficult to draw
      quantitative conclusions from the clinical data. The objective of this study was
      to quantitatively compare the effects of bleach and peracetic acid cleaning on
      the clearance and surface charge characteristics of Fresenius F80B polysulfone
      dialyzers (Fresenius Medical Care, Lexington, MA, USA). Clearance experiments
      were performed using urea, vitamin B(12), and polydisperse dextrans, with data
      obtained before and after exposure to human plasma in an in vitro dialysis
      circuit. Dialyzers cleaned with peracetic acid had significantly lower clearance
      of the larger dextrans due to the presence of residual protein on or within the
      membrane. Bleach was able to remove this protein deposit, restoring the clearance
      characteristics, but there was a significant increase in the net negative charge
      of the membrane due to chemical reaction with the bleach. In addition, longer
      time exposure to bleach altered the membrane transport characteristics,
      increasing the solute clearance. These results provide important insights into
      the effects of bleach and peracetic acid on the properties of the F80B dialyzers.

PMID- 17537058
TI  - Argatroban in extracorporeal membrane oxygenation.
AB  - The objective of this study was to assess the required dose and anticoagulatory
      effect of argatroban (Mitsubishi, Pharma Deutschland GmbH, Dusseldorf, Germany),
      a direct thrombin inhibitor approved for anticoagulation in patients with heparin
      induced thrombocytopenia (HIT) undergoing extracorporeal membrane oxygenation
      (ECMO). Nine consecutive patients undergoing ECMO for severe acute respiratory
      distress syndrome (ARDS) and presenting with suspected HIT were treated with a
      continuous argatroban infusion. Coagulation variables were measured and dose
      adjustments of argatroban were performed to target for an activated partial
      thromboplastin time (aPTT) of 50 to 60 s. The first patient received argatroban 2
      microg/kg/min as recommended by the manufacturer. This resulted in excessive
      anticoagulation and severe bleeding. The consecutive eight patients received a 10
      fold lower dose (0.2 microg/kg/min). This dose sufficiently increased aPTT time
      from 46 +/- 6 s to 65 +/- 14 s (P < 0.001) and thrombin time from 18 +/- 8 s to
      45 +/- 11 s (P = 0.001). The maintenance dose averaged 0.15 microg/kg/min.
      Duration of argatroban infusion for ECMO averaged 4 +/- 1 days and no oxygenator
      or extracorporeal system clotting was observed. In three of nine patients (33%),
      HIT was confirmed. Argatroban is a feasible and effective anticoagulant for
      patients with suspected HIT undergoing ECMO. However, a dose 10-fold lower than
      that recommended by the manufacturer is sufficient to achieve appropriate
      anticoagulation in critically ill patients undergoing ECMO.

PMID- 17537059
TI  - Plasma protein binding properties to immobilized heparin and heparin-albumin
      conjugate.
AB  - Selective adhesion of plasma proteins to immobilized heparin is considered to be
      beneficial regarding hemocompatibility of foreign materials in contact with
      blood. Prothrombin, thrombin, antithrombin III (AT3), and fibrinogen were
      selected for analysis in an experimental model. Biomolecular interaction analysis
      employing surface plasmon resonance was utilized to record and analyze their
      binding properties in real time. Biotinylated heparin, heparin-albumin conjugate,
      and albumin, respectively, were immobilized onto streptavidin-coated sensors as
      ligands. Prothrombin did not bind to any of the ligand surfaces and no specific
      binding of any of the plasma proteins to albumin was observed. Binding kinetics
      of thrombin to heparin and to heparin-albumin conjugate were calculated using two
      different methods. For heparin, identical K(D)(equilibrium dissociation constant)
      values of 61 x 10(-9) M were obtained with both methods. For the conjugate, only
      slightly different K(D) values of 111 x 10(-9) and 104 x 10(-9) M, respectively,
      were calculated. The affinity of thrombin toward the heparin-coated surface
      proved to be higher than its affinity toward the heparin conjugate. The binding
      pattern of AT3 to both heparin and heparin-albumin conjugate, although specific,
      was biphasic, possibly due to a conformational change during the binding process.
      Steady-state kinetic analysis revealed a K(D) value of 281 +/- 24 x 10(-9) M for
      the heparin surface. For the conjugate surface, a K(D) of 53 +/- 5 x 10(-9) M was
      calculated, indicating a higher affinity toward heparin-albumin conjugate. A high
      affinity binding of fibrinogen to high-density surfaces of both heparin and the
      conjugate was observed. However, as binding to low-density surfaces was
      considerably reduced, specificity remained uncertain.

PMID- 17537060
TI  - Intermittent stops of shear reduce the mechanical damage of red blood cells.
AB  - Continuous and intermittent high shear were loaded to red blood cells in a cone
      and a plate rheoscope. The mechanical damage to red cells was compared for
      continuous and intermittent shear. The intermittent shear was achieved by
      alternately starting and stopping shear repeatedly. In the case of intermittent
      shear load, red cell damage was suppressed remarkably. To explain this effect, we
      introduced a phenomenological hemolysis model, which agreed reasonably with the
      hemolysis tests for intermittent shear flow.

PMID- 17537061
TI  - Classification of physiologically significant pumping states in an implantable
      rotary blood pump: effects of cardiac rhythm disturbances.
AB  - Methods of speed control for implantable rotary blood pumps (iRBPs) are vital for
      providing implant recipients with sufficient blood flow to cater for their
      physiological requirements. The detection of pumping states that reflect the
      physiological state of the native heart forms a major component of such a control
      method. Employing data from a number of acute animal experiments, five such
      pumping states have been previously identified: regurgitant pump flow,
      ventricular ejection (VE), nonopening of the aortic valve (ANO), and partial
      collapse (intermittent [PVC-I] and continuous [PVC-C]) of the ventricle wall. An
      automated approach that noninvasively detects such pumping states, employing a
      classification and regression tree (CART), has also been developed. An extension
      to this technique, involving an investigation into the effects of cardiac rhythm
      disturbances on the state detection process, is discussed. When incorporating
      animal data containing arrhythmic events into the CART model, the strategy showed
      a marked improvement in detecting pumping states as compared to the model devoid
      of arrhythmic data: state VE--57.4/91.7% (sensitivity/specificity) improved to
      97.1/100.0%; state PVC-I--66.7/83.1% improved to 100.0/88.3%, and state PVC-C-
      11.1/66.2% changed to 0.0/100%. With a simplified binary scheme differentiating
      suction (PVC-I, PVC-C) and nonsuction (VE, ANO) states, suction was initially
      detected with 100/98.5% sensitivity/specificity, whereas with the subsequent
      improved model, both these states were detected with 100% sensitivity. The
      accuracy achieved demonstrates the robustness of the technique presented, and
      substantiates its inclusion into any iRBP control methodology.

PMID- 17537062
TI  - Relationship between biometric characteristics and stem size of uncemented hip
      prostheses.
AB  - The authors examined 2329 uncemented hip prosthesis stems (AncaFit stem, Wright
      Medical Technology, Arlington, TN, USA) implanted between 1996 and 2004 due to
      primary coxarthrosis. This is the most commonly used stem in the Emilia-Romagna
      region, in northern Italy, according to data from the Register of Orthopaedic
      Prosthetic Implants (RIPO). It is produced in eight sizes for each side. We
      analyzed the relationship between stem size and anthropometric data. Among the
      patients, 49.5% were men and 50.5% were women; mean age at surgery was 64.1 years
      (SD 9.1); mean height was 167 cm (SD 8.4), and mean weight was 75.7 kg (SD 12.7).
      Multifactorial analysis demonstrated that stem size was influenced by sex, age,
      and height, but not by weight. Besides this, there was an interaction between sex
      and age: in women, but not in men, the stem size increased with aging.

PMID- 17537063
TI  - Development of air micro bubbles in the venous outlet line: an in vitro analysis
      of various air traps used for hemodialysis.
AB  - Venous air traps were tested in vitro with respect to presence of micro bubbles.
      Three types of venous air traps were measured (Bioline, Bioline GmbH,
      Luckenwalde, Germany; Gambro, Gambro AB, Lund, Sweden; Fresenius M.C., Fresenius
      Medical Care AG & Co. KGaA, Bad Homburg, Germany). Measurements (n = 10) were
      taken for each air trap, fluid flow (50-600 mL/min), and fluid level (high/low).
      A 1.5-MHz ultrasound probe was used with an analysis device. The probe was
      mounted on the outlet line downstream of the venous air trap. A semisynthetic
      fluid was used to resemble blood viscosity. Occurrences of micro bubbles, without
      inducing an alarm of the dialysis device, were detected in almost all
      measurements. The amount of bubbles increased with increasing flow. There were
      more bubbles with low fluid level compared with high level. The Bioline tubing
      released the least bubbles in high fluid level. At low level, the Gambro tubing
      showed the least bubbles at flows 50-400 mL/min, and the Fresenius M.C. tubing
      showed the least bubbles at flows 400-600 mL/min. High fluid level in the air
      trap reduced generation of micro bubbles compared to low level, as did lower
      fluid flow versus high flow. The design of the air trap was also of importance.

PMID- 17537064
TI  - Induction of metallothionein in mesothelial cells by zinc.
AB  - Patients on peritoneal dialysis (PD) are exposed to peritoneal dialysis fluids
      with unphysiological properties. Local defense systems are of importance. In this
      respect, metallothionein (MT) might play an important role. Because nothing is
      known about the achievability of MT induction in peritoneum by zinc, we performed
      the following study. We investigated human peritoneal mesothelial cells (HPMC)
      from omentum and a mesothelioma cell (MTC) line after addition of zinc in
      concentrations from 35 to 350 microM. Measurements of MT-mRNA and protein (by
      immuncytochemistry [IHC], Western blots, and dot blots) were performed. Zinc
      caused a clear and highly significant fourfold increase of RNA in MTC and to a
      lower extent in HPMC (1.6-fold, P < 0.001). IHC demonstrated a clear induction in
      HPMC and MTC. Western and dot blots confirmed this and showed an increase of MT
      from 112-mg/g total protein (TP) to 410-mg/g TP. Zinc was able to upregulate MT
      significantly in HPMC and MTC on the RNA and protein level. Fourfold increases of
      MT were achievable.

PMID- 17537066
TI  - Failure of hemodiafiltration to suppress blood citrate levels during plasma
      exchange.

PMID- 17537068
TI  - The time has come, the Walrus said, 'To speak of many things; Of shoes and ships
      and sealing wax, Of cabbages and kings'.

PMID- 17537069
TI  - Research Review: Can we justify the widespread dissemination of universal, school
      based interventions for the prevention of depression among children and
      adolescents?
AB  - This review examines the evidence concerning the efficacy and effectiveness of
      universal, school-based interventions designed to prevent the development of
      depression in children and adolescents. It evaluates the outcomes of research in
      relation to standards of evidence specified by the Society for Prevention
      Research (Flay et al., 2005). The limited evidence available brings into doubt
      the efficacy and effectiveness of current universal, school-based approaches to
      the prevention of depression, suggesting that the widespread dissemination of
      such interventions would be premature. Relatively brief programs, that focus
      specifically on enhancing individual skills and characteristics of the individual
      in the absence of environmental change, may be insufficient to produce lasting
      effects in the prevention of depression among children and adolescents.

PMID- 17537070
TI  - Variation in community intervention programmes and consequences for children and
      families: the example of Sure Start Local Programmes.
AB  - BACKGROUND: An area-based initiative, Sure Start Local Programmes (SSLPs), was
      established by the UK government to reduce social exclusion through improving the
      well-being of children aged 0-3 years and their families in disadvantaged
      communities; a true community intervention in that all children under four and
      their families in specified areas served as targets of universal services. A
      national evaluation examined the links between variation in programme
      implementation and effectiveness. METHODS: Data gathered from multiple sources
      produced measures of implementation in terms of proficiency, services and
      staffing. Measures of programme impact on child/parenting outcomes derived from
      multilevel models, controlling for child, family and area characteristics, were
      identified to demonstrate programme effectiveness. RESULTS: Some modest linkage
      between programme implementation (e.g., proficiency, empowerment of parents and
      staff, identification of users) and effectiveness for child and parenting
      outcomes. CONCLUSIONS: Overall proficiency and specific aspects of implementation
      may influence effectiveness, which should guide the design of other child, family
      and community services.

PMID- 17537071
TI  - A randomised controlled treatment trial of two forms of family therapy in
      adolescent anorexia nervosa: a five-year follow-up.
AB  - BACKGROUND: There is growing evidence that family therapy is an effective
      treatment for adolescent anorexia nervosa. This study aimed to ascertain the long
      term impact of two forms of outpatient family intervention previously evaluated
      in a randomised controlled trial (RCT). METHOD: A five-year follow-up was
      conducted on a cohort of 40 patients who had received either 'conjoint family
      therapy' (CFT) or 'separated family therapy' (SFT). All patients were traced and
      38 agreed to be reassessed (29 interviewed in person, 3 completed telephone
      interviews, 6 completed questionnaires and/or agreed for parents/GP to be
      interviewed). RESULTS: Overall there was little to distinguish the two treatments
      at 5 years, with more than 75% of subjects having no eating disorder symptoms.
      There were no deaths in the cohort and only 8% of those who had achieved a
      healthy weight by the end of treatment reported any kind of relapse. Three
      patients developed bulimic symptoms but only one to a degree warranting a
      diagnosis of bulimia nervosa. The one difference between the treatments was in
      patients from families with raised levels of maternal criticism. This group of
      patients had done less well at the end of treatment if they had been offered
      conjoint family meetings. At follow-up this difference was still evident, as
      shown in the relative lack of weight gain since the end of outpatient treatment.
      CONCLUSIONS: This study confirms the efficacy of family therapy for adolescent
      anorexia nervosa, showing that those who respond well to outpatient family
      intervention generally stay well. The study provides further support for avoiding
      the use of conjoint family meetings at least early on in treatment when raised
      levels of parental criticism are evident.

PMID- 17537072
TI  - Sleep patterns in children with attention-deficit/hyperactivity disorder, tic
      disorder, and comorbidity.
AB  - BACKGROUND: In children, attention-deficit/hyperactivity disorder (ADHD), tic
      disorder (TD), and their coexistence (ADHD + TD comorbidity) are very common and
      clinically important. Associated sleep patterns and their clinical role are still
      insufficiently investigated. This study aimed at characterizing these sleep
      patterns in children with ADHD, TD, and ADHD + TD comorbidity and determining
      whether, in ADHD + TD, the factors ADHD and TD may affect the sleep pattern in an
      independent (additive) or in a complex (interactive) manner. METHOD: By means of
      polysomnography, sleep patterns were investigated in 4 groups of unmedicated 8.0
      16.4-year-old children (healthy controls, ADHD-only, TD-only, and ADHD + TD).
      Each group consisted of 18 subjects matched for age, gender, and intelligence.
      RESULTS: ADHD was primarily characterized by increase in rapid eye movement (REM)
      sleep, whereas TD patients displayed lower sleep efficiency and elevated arousal
      index in sleep. In children with ADHD + TD, both effects appeared. No interaction
      between the ADHD and TD factors was found for any of the sleep parameters.
      Significant correlations between sleep patterns and clinical symptoms were found.
      CONCLUSIONS: ADHD and TD are characterized by specific sleep alterations. When
      coexisting, the two disorders alter the sleep pattern in an additive manner,
      suggesting a high impact on clinical and therapeutic perspectives.

PMID- 17537073
TI  - Genomic imprinting and the expression of affect in Angelman syndrome: what's in
      the smile?
AB  - BACKGROUND: Kinship theory (or the genomic conflict hypothesis) proposes that the
      phenotypic effects of genomic imprinting arise from conflict between paternally
      and maternally inherited alleles. A prediction arising for social behaviour from
      this theory is that imbalance in this conflict resulting from a deletion of a
      maternally imprinted gene, as in Angelman syndrome (AS), will result in a
      behavioural phenotype that should evidence behaviours that increase access to
      maternally provided social resources (adult contact). METHOD: Observation of the
      social behaviour of children with AS (n = 13), caused by a deletion at 15q11-q13,
      and a matched comparison group (n = 10) was undertaken for four hours in a
      socially competitive setting and the effect of adult attention on child
      behaviours and the effect of child smiling on adult behaviours evaluated using
      group comparisons and observational lag sequential analyses. RESULTS: The AS
      group smiled more than the comparison group in all settings, which had different
      levels of adult attention, and more when the level of adult attention was high.
      Smiling by children with AS evoked higher levels of adult attention, eye contact
      and smiling both than by chance and in comparison to other children and this
      effect was sustained for 30 s to 50 s. Smiling by children with AS was frequently
      preceded by child initiated contact toward the adult. DISCUSSION: The results are
      consistent with a kinship theory explanation of the function of heightened levels
      of sociability and smiling in Angelman syndrome and provide support for an
      emotion signalling interpretation of the mechanism by which smiling accesses
      social resources. Further research on other behaviours characteristic of Angelman
      and Prader-Willi syndromes warrant examination from this perspective.

PMID- 17537074
TI  - Salivary dehydroepiandrosterone responsiveness to social challenge in adolescents
      with internalizing problems.
AB  - BACKGROUND: Dehydroepiandrosterone (DHEA) is an adrenal androgen which is stress
      responsive and a trigger for pubertal maturation. Studies on basal DHEA suggest
      protective benefits against anxiety and depression, yet it is unknown whether
      DHEA responsivity is protective. METHODS: Structural equation modeling examined
      salivary DHEA responses to a public speaking task (PST) and parent-child conflict
      discussion paradigm (CDP) in adolescents. RESULTS AND CONCLUSIONS: DHEA levels
      were higher in girls than boys, and in older and more physically developed
      adolescents, indicative of DHEA's function during pubertal maturation. DHEA
      levels increased during the PST, indicating responsiveness of DHEA to acute
      stressors. Across both tasks, girls with internalizing problems showed sharper
      rises in DHEA by 40 minutes post-task, ending with the highest DHEA. In
      internalizing adolescent girls, DHEA may serve as a marker of responsivity in
      stressful or conflictual contexts. A failure of these girls with internalizing
      problems to show a normal diurnal decline in the afternoon extended this
      conclusion to naturalistic environments. DHEA may be one possible mechanism
      linking stress responsivity and physical maturation that helps to explain
      adolescents' risk for psychopathology within a biobehavioral framework.

PMID- 17537076
TI  - Which better predicts conduct problems? The relationship of trajectories of
      conduct problems with ODD and ADHD symptoms from childhood into adolescence.
AB  - BACKGROUND: To assess the co-occurrence in deviant trajectories of parent-rated
      symptoms of conduct disorder (CD), oppositional defiant disorder (ODD) and
      attention-deficit/hyperactivity disorder (ADHD) from age 4 to 18 years old in a
      general population sample of Dutch children. METHODS: Developmental trajectories
      of CD, ODD, and ADHD were estimated in a sample of 1,016 males and 1,060 females.
      Children's disruptive problem behaviors were rated at 5 time-points. The co
      occurrence patterns between the deviant CD trajectory, and the high ODD and high
      ADHD trajectory were studied for males and females separately. RESULTS: Four
      percent of males and 2% of females followed a deviant CD trajectory. Six percent
      of the sample followed a high ODD trajectory, and 5% a high ADHD trajectory.
      Engagement in the deviant CD trajectory was predicted by ODD and ADHD in females,
      but only by ODD in males. CONCLUSIONS: Although ADHD co-occurs with CD, the
      association between ADHD and CD is largely accounted for by accompanying ODD.
      Gender differences should be taken into account in understanding the onset of CD.

PMID- 17537075
TI  - Depressive symptoms in adolescents: associations with white matter volume and
      marijuana use.
AB  - BACKGROUND: Depressed mood has been associated with decreased white matter and
      reduced hippocampal volumes. However, the relationship between brain structure
      and mood may be unique among adolescents who use marijuana heavily. The goal of
      this study was to examine the relationship between white matter and hippocampal
      volumes and depressive symptoms among adolescent marijuana users and controls.
      METHODS: Data were collected from marijuana users (n = 16) and demographically
      similar controls (n = 16) aged 16-18. Extensive exclusionary criteria included
      psychiatric and neurologic disorders, including major depression. Substance use,
      mood, and anatomical measures were collected after 28 days of monitored
      abstinence. RESULTS: Marijuana (MJ) users demonstrated more depressive symptoms
      than controls (p < .05). MJ use (beta = .42, p < .005) and smaller white matter
      volume (beta = -.34, p < .03) each predicted higher levels of depressive symptoms
      on the Hamilton Depression Rating Scale. MJ use interacted with white matter
      volume (beta = -.55, p < .03) in predicting depression scores on the Beck
      Depression Inventory: among MJ users, but not controls, white matter volume was
      negatively associated with depressive symptoms. CONCLUSIONS: Marijuana use and
      white matter volume were additive and interactive in predicting depressive
      symptoms among adolescents. Subtle neurodevelopmental white matter abnormalities
      may disrupt the connections between areas involved in mood regulation.

PMID- 17537077
TI  - Children at family risk of dyslexia: a follow-up in early adolescence.
AB  - BACKGROUND: This study is the follow-up in early adolescence of children born to
      families with a history of dyslexia (Gallagher, Frith, & Snowling, 2000).
      METHODS: Fifty young people with a family history of dyslexia and 20 young people
      from control families were assessed at 12-13 years on a battery of tests of
      literacy and language skills, and they completed questionnaires tapping self
      perception and print exposure. One parent from each family participated in an
      interview documenting family circumstances (including family literacy) and a
      range of environmental variables considered likely correlates of reading
      disability. They also rated their child's behavioural and emotional adjustment
      and their own health and well-being. Parental literacy levels were also measured.
      RESULTS: Forty-two per cent of the 'at-risk' sample had reading and spelling
      impairments. A significant proportion of the literacy-impaired group were
      affected by behavioural and emotional difficulties, although they were not low in
      terms of global self-esteem. The children in the at-risk subgroup who did not
      fulfil criteria for literacy impairment showed weak orthographic skills in
      adolescence and their reading was not fluent. There were no differences in the
      literacy levels or activities of the parents of impaired and unimpaired at-risk
      children, and no significant correlation between parent and child reading levels
      in the at-risk group. The impaired group read less than the other groups, their
      reading difficulties impacted learning at school and there was evidence that they
      also had an impact on family life and maternal well-being. CONCLUSIONS: The
      literacy difficulties of children at family-risk of dyslexia were longstanding
      and there was no evidence of catch-up in these skills between 8 and 13 years. The
      findings point to the role of gene-environment correlation in the determination
      of dyslexia.

PMID- 17537078
TI  - Prevalence and correlates of partner violence among South African adolescents.
AB  - BACKGROUND: Little is known about the prevalence of partner violence among
      adolescents, nor of the factors with which it is associated. The objectives of
      this study were to document prevalence rates for partner violence among high
      school students in Cape Town, and to explore factors that are associated with
      such violence. METHOD: The sample consisted of 596 Grade 8 and 11 students
      attending public high schools in Cape Town, who were selected using a multistage
      cluster design. They completed an anonymous and confidential questionnaire. The
      dependent variable was whether they had ever perpetrated partner violence, or
      intended to do so. The independent variables, which were derived from a modified
      version of the Theory of Planned Behaviour (TPB), included attitudes, subjective
      norms (general and peer social influence and outcome expectancy) and self
      efficacy. Separate multiple logistic regression models were developed of partner
      violence intentions or behaviours on the scales derived from the TPB and
      demographic variables. Regression coefficients from adjusted models were used to
      examine the potential mediating role of partner violence intentions in the
      association between each scale and partner violence behaviours using the Sobel
      test. RESULTS: Among participants who reported being in a relationship, 20.7%
      reported perpetrating partner violence, and 16.4% reported intending to do so.
      After adjusting for demographic characteristics and other predictor scales,
      perpetration of partner violence was significantly associated with attitudes and
      outcome expectancy, while intention to perpetrate partner violence was
      significantly associated with attitudes and general social influence. The
      influence of attitude and general social influence on violent behaviours were
      each partially mediated by partner violence intentions. CONCLUSIONS: There are
      high levels of partner violence among high school students in Cape Town.
      Interventions to address this problem should focus on violence-related attitudes
      and outcome expectancy.

PMID- 17537079
TI  - American Geriatrics Society turns 65.

PMID- 17537080
TI  - Magnitude of underascertainment of impaired kidney function in older adults with
      normal serum creatinine.
AB  - OBJECTIVES: To estimate in a community-dwelling elderly population the magnitude
      of renal function misclassification, occurring when persons with normal serum
      creatinine have reduced glomerular filtration rate (GFR), and to describe the
      participant characteristics related to misclassification. DESIGN: Cross
      sectional. SETTING: Population-based study of older Italian people. PARTICIPANTS:
      Six hundred sixty participants aged 65 to 92 with normal serum creatinine.
      MEASUREMENTS: GFR was estimated using the Cockcroft-Gault equation and creatinine
      clearance (CrCl) calculated from 24-hour urine collection. RESULTS: In
      participants with normal serum creatinine, 39% and 25% had moderate renal
      function impairment (GFR<60 mL/min) according to the Cockcroft-Gault equation and
      CrCl calculation, respectively. Prevalence of moderate renal impairment in those
      aged 65 to 74, 75 to 84, and 85 and older was 18.6%, 58.3%, and 96.8%,
      respectively (P for trend <.001) according to the Cockcroft-Gault equation, and
      15%, 35.7%, and 58.7%, respectively (P for trend <.001) based on the CrCl
      calculation. In addition, female sex (P<.001) and normal or underweight (P<.05)
      were factors associated with high risk of misclassification. CONCLUSION: Serum
      creatinine alone is one of the most widely used methods of assessing renal
      function in clinical practice despite its well-known poor correlation with GFR. A
      large proportion of older persons with impaired renal function are not diagnosed
      if clinicians rely solely on normal serum creatinine as evidence of normal renal
      function. Opportunities may be missed for slowing progression of kidney disease,
      managing comorbidities and complications related to renal impairment, and
      adjusting drug dosage for renal function.

PMID- 17537081
TI  - Depressive symptoms and rates of bone loss at the hip in older women.
AB  - OBJECTIVES: To ascertain whether depressive symptoms are associated with
      increased rates of bone loss at the hip. DESIGN: Population-based prospective
      cohort study. SETTING: Four clinical centers in the United States. PARTICIPANTS:
      Four thousand one hundred seventy-seven community-dwelling women, aged 69 and
      older, enrolled in the Study of Osteoporotic Fractures. MEASUREMENTS: Depressive
      symptoms were assessed using the Geriatric Depression Scale (GDS). Subjects were
      categorized as depressed if their GDS score was 6 or greater at the fourth
      examination. Bone mineral density (BMD) at the hip was measured using dual-energy
      x-ray absorptiometry at the fourth and sixth examinations (average 4.4 years
      between examinations). Use of antidepressant medications was assessed by
      interview and verified from medication containers at the fourth and sixth
      examinations of the Study of Osteoporotic Fractures. A computerized dictionary
      was used to categorize type of medication. RESULTS: In age-adjusted models, mean
      total hip BMD decreased 0.69%/year in 3,977 women with a GDS score of less than
      6, compared with 0.96%/year in 200 women with a GDS score of 6 or greater
      (P<.01). Results were not substantially altered when adjusted for potential
      confounders and when users of antidepressants were excluded from the analysis.
      CONCLUSION: Depression, as defined by a GDS score of 6 or greater, was associated
      with an increased rate of bone loss at the hip in this cohort of older women.
      Clinicians should be aware of a possible increased rate of bone loss in older,
      depressed women.

PMID- 17537082
TI  - Resident outcomes in small-house nursing homes: a longitudinal evaluation of the
      initial green house program.
AB  - OBJECTIVES: To determine the effects of a small-house nursing home model, THE
      GREEN HOUSE (GH), on residents' reported outcomes and quality of care. DESIGN:
      Two-year longitudinal quasi-experimental study comparing GH residents with
      residents at two comparison sites using data collected at baseline and three
      follow-up intervals. SETTING: Four 10-person GHs, the sponsoring nursing home for
      those GHs, and a traditional nursing home with the same owner. PARTICIPANTS: All
      residents in the GHs (40 at any time) at baseline and three 6-month follow-up
      intervals, and 40 randomly selected residents in each of the two comparison
      groups. INTERVENTION: The GH alters the physical scale environment (small-scale,
      private rooms and bathrooms, residential kitchen, dining room, and hearth), the
      staffing model for professional and certified nursing assistants, and the
      philosophy of care. MEASUREMENTS: Scales for 11 domains of resident quality of
      life, emotional well-being, satisfaction, self-reported health, and functional
      status were derived from interviews at four points in time. Quality of care was
      measured using indicators derived from Minimum Data Set assessments. RESULTS:
      Controlling for baseline characteristics (age, sex, activities of daily living,
      date of admission, and proxy interview status), statistically significant
      differences in self-reported dimensions of quality of life favored the GHs over
      one or both comparison groups. The quality of care in the GHs at least equaled,
      and for change in functional status exceeded, the comparison nursing homes.
      CONCLUSION: The GH is a promising model to improve quality of life for nursing
      home residents, with implications for staff development and medical director
      roles.

PMID- 17537083
TI  - Resident-to-resident elder mistreatment and police contact in nursing homes:
      findings from a population-based cohort.
AB  - OBJECTIVES: To determine the frequency and nature of police contact with a well
      characterized cohort of originally community-dwelling older adults who were
      subsequently placed in long-term care facilities and to describe in more
      quantitative and qualitative detail episodes of resident-to-resident elder
      mistreatment (RREM), which constituted the most common reason for police
      involvement in long-term care facilities. DESIGN: Qualitative and quantitative
      study of the characteristics of nursing home residents who engaged in resident-to
      resident mistreatment. The study melded longitudinal data from an observational
      cohort of community-dwelling older adults subsequently placed in long-term care
      facilities and cross-sectional data from nursing home and police records.
      SETTING: Nursing homes. PARTICIPANTS: Forty-two of 747 older adults placed in
      long-term care facilities who were members of the original New Haven Established
      Populations for Epidemiological Studies in the Elderly (EPESE) were involved in
      79 separate incidents. These 747 nursing home residents were derived from 2,321
      subjects in the study who were alive and community dwelling in 1985 and then
      subsequently placed in nursing homes between 1985 and 1995. EPESE cohort members
      who were placed in nursing homes were identified through a linkage to the
      Connecticut Long-Term Care Registry. The cohort was also linked to police records
      in the same community for the follow-up years 1985 to 1995. MEASUREMENTS: Simple
      descriptive statistics were used to explicate reasons for police calls to the
      long-term care facilities where these individuals resided. Demographic and
      clinical data were obtained from annual EPESE interviews, which continued after
      long-term care placement. Police incident reports were abstracted to determine
      the reasons for police involvement; transcripts of police reports were reviewed
      qualitatively for episodes of RREM. RESULTS: During the follow-up period, police
      were called to investigate 79 incidents involving 42 cohort members placed in
      nursing homes. The most common reason (89% of incidents) for police to
      investigate an episode involving a cohort member was for simple assault in which
      the subject was the perpetrator or victim of resident-to-resident mistreatment.
      Several qualitative typologies of this phenomenon emerged. Less common causes for
      police interdiction were elopement, theft, and alleged staff abuse. Cohort
      members were more likely to interact with police when community dwelling than
      after they entered the nursing home (30.2% vs 5.6%, P<.001). When police contact
      occurred with nursing home residents, it was much more likely to be for violent
      episodes than in community-dwelling subjects (90% vs 17%, P<.001). CONCLUSION:
      Police had substantial contact with cohort members who became nursing home
      residents in this study, primarily to investigate RREM but also for other
      incidents. Further research should be conducted on the epidemiology, causes, and
      prevention of resident-to-resident aggressive behaviors in long-term care
      facilities, which were the major reason for police involvement.

PMID- 17537084
TI  - Physician communication with family caregivers of long-term care residents at the
      end of life.
AB  - OBJECTIVES: To assess family perceptions of communication between physicians and
      family caregivers of individuals who spent their last month of life in long-term
      care (LTC) and to identify associations between characteristics of the family
      caregiver, LTC resident, facility, and physician care with these perceptions.
      DESIGN: Retrospective study of family caregivers of persons who died in LTC.
      SETTING: Thirty-one nursing homes (NHs) and 94 residential care/assisted living
      (RC/AL) facilities. PARTICIPANTS: One family caregiver for each of 440 LTC
      residents who died (response rate 66.0%) was interviewed 6 weeks to 6 months
      after the death. MEASUREMENTS: Demographic and facility characteristics and seven
      items rating the perception of family caregivers regarding physician-family
      caregiver communication at the end of life, aggregated into a summary scale,
      Family Perception of Physician-Family caregiver Communication (FPPFC) (Cronbach
      alpha=0.96). RESULTS: Almost half of respondents disagreed that they were kept
      informed (39.9%), received information about what to expect (49.8%), or
      understood the doctor (43.1%); the mean FPPFC score (1.73 on a scale from 0 to 3)
      was slightly above neutral. Linear mixed models showed that family caregivers
      reporting better FPPFC scores were more likely to have met the physician face to
      face and to have understood that death was imminent. Daughters and daughters-in
      law tended to report poorer communication than other relatives, as did family
      caregivers of persons who died in NHs than of those who died in RC/AL facilities.
      CONCLUSION: Efforts to improve physician communication with families of LTC
      residents may be promoted using face-to-face meetings between the physician and
      family caregivers, explanation of the patient's prognosis, and timely conveyance
      of information about health status changes, especially when a patient is actively
      dying.

PMID- 17537085
TI  - The effect of age on short-term outcomes after abdominal surgery for pelvic organ
      prolapse.
AB  - OBJECTIVES: To compare perioperative morbidity and 1-year outcomes of older and
      younger women undergoing surgery for pelvic organ prolapse (POP). DESIGN:
      Prospective ancillary analysis. SETTING: Academic medical centers in National
      Institutes of Health, National Institute of Child Health and Human Development
      Colpopexy and Urinary Reduction Study. PARTICIPANTS: Women with POP and no
      symptoms of stress incontinence. INTERVENTION: Abdominal sacrocolpopexy with
      randomization to receive Burch colposuspension for treatment of possible occult
      incontinence or not. MEASUREMENTS: Perioperative complications and Pelvic Organ
      Prolapse Quantification and quality-of-life (QOL) questionnaires (Pelvic Floor
      Distress Inventory, Pelvic Floor Impact Questionnaire, and Medical Outcomes Study
      Short-Form Health Survey (SF-36) preoperatively, immediately postoperatively, and
      6 weeks and 3 and 12 months postoperatively). RESULTS: Three hundred twenty-two
      women aged 31 to 82 (21% aged > or =70), 93% white. Older women had higher
      baseline comorbidity (P<.001) and more severe POP (P=.003). Controlling for
      prolapse stage and whether Burch was performed, there were no age differences in
      complication rates. Older women had longer hospital stays (3.1+/-1.0 vs 2.7+/-1.5
      days, P=.02) and higher prevalence of incontinence at 6 weeks (54.7% vs 37.2%,
      P=.005). At 3 and 12 months, there were no differences in self-reported
      incontinence, stress testing for incontinence, or prolapse stage. Improvements
      from baseline were significant on all QOL measures but with no age differences.
      CONCLUSION: Outcomes of prolapse surgery were comparable between older and
      younger women except that older women had slightly longer hospital stays.

PMID- 17537086
TI  - Inflammation and frailty in older women.
AB  - OBJECTIVES: To evaluate relationships between white blood cell (WBC) count and
      interleukin-6 (IL-6) and prevalent frailty. DESIGN: Cross-sectional study.
      SETTING: Two population-based studies, the Women's Health and Aging Studies
      (WHAS) I and II, Baltimore, Maryland. PARTICIPANTS: Five hundred fifty-eight
      women aged 65 to 101 from WHAS I and 548 women aged 70 to 79 from the merged WHAS
      I and II cohorts. MEASUREMENTS: Frailty was determined using validated screening
      criteria. WBC counts and IL-6 levels were measured using standard laboratory
      methods. Odds ratios (ORs) for frailty were evaluated across tertiles of baseline
      WBC counts and IL-6 levels, adjusting for age, race, education, body mass index,
      and smoking status. RESULTS: In WHAS I, those in the top tertile of WBC count and
      IL-6 had ORs of 4.25 (95% confidence interval (CI)=1.89-9.58) and 3.98 (95%
      CI=1.76-9.00), respectively, for frailty (both P<.001). In the combined models,
      participants in the top tertile of WBC count had an OR of 3.15 (95% CI=1.34
      7.41), adjusting for IL-6 (P<.01), and those in the top tertile of IL-6 had an OR
      of 2.81 (95% CI=1.19-6.64), adjusting for WBC count (P<.05). Furthermore,
      participants in the top tertiles of WBC count and IL-6 had an OR of 9.85 (95%
      CI=3.04-31.99), and those in the middle/top tertiles had an OR of 5.40 (95%
      CI=1.83-15.92) (P<.001, trend test) for frailty. These results were validated in
      the merged WHAS I and II. CONCLUSION: Higher WBC counts and IL-6 levels were
      independently associated with prevalent frailty in community-dwelling older
      women.

PMID- 17537087
TI  - The routine electrocardiogram for cardiovascular risk stratification in old age:
      the Leiden 85-plus study.
AB  - OBJECTIVES: To explore the prognostic value of signs of prior myocardial
      infarction (MI) and atrial fibrillation (AF) on routine electrocardiograms (ECGs)
      at the age of 85 with respect to mortality and changes in functional status.
      DESIGN: Observational, prospective cohort study with complete 6-year follow-up.
      SETTING: General population. PARTICIPANTS: A population-based sample of 566 85
      year-old participants (377 women, 189 men), without exclusion criteria.
      MEASUREMENTS: Annual ECG recording and evaluation using automated Minnesota
      Coding; annual assessment of functional status using validated questionnaires and
      tests; complete mortality data from civic and national registries. RESULTS:
      Participants with prior MI at the age of 85 (prevalence 9%) showed greater all
      cause mortality (relative risk (RR)=1.7, 95% confidence interval (CI)=1.2-2.2)
      and cardiovascular mortality (RR=2.5, 95% CI=1.6-3.8) but no accelerated decline
      in functional status during follow-up. Participants with AF at the age of 85
      (prevalence 10%) showed greater all-cause (RR=1.5, 95% CI=1.2-2.0) and
      cardiovascular (RR=2.0, 95% CI=1.3-3.0) mortality, as well as an accelerated
      decline in functional status during follow-up. CONCLUSION: Very elderly people
      with prior MI or AF on a routine ECG have markedly greater (cardiovascular)
      mortality risks. In addition, AF, but not prior MI, is associated with
      accelerated decline in functional status. These findings suggest that older
      patients with occasional findings of prior MI or AF on a routine ECG should
      receive optimal secondary preventive therapy. Furthermore, programmatic ECG
      recording could be of significant value for cardiovascular risk stratification in
      old age and needs further exploration.

PMID- 17537088
TI  - Systematic review of driving risk and the efficacy of compensatory strategies in
      persons with dementia.
AB  - OBJECTIVES: To determine whether persons with dementia are at greater driving
      risk and, if so, to estimate the magnitude of this risk and determine whether
      there are efficacious methods to compensate for or accommodate it. DESIGN:
      Systematic review of the literature. SETTING: Case-control studies. PARTICIPANTS:
      Drivers with a diagnosis of dementia. MEASUREMENTS: Most studies used state and
      caregiver reported crash rates, performance-based road tests, and driving
      simulator evaluations as their outcome measures. RESULTS: Twenty-three studies
      were included. Drivers with dementia universally exhibited poorer performance on
      road tests and simulator evaluations, although only one study using an objective
      measure of motor vehicle crashes was able to show that drivers with dementia were
      involved in more crashes than control subjects. No studies were found that
      examined the efficacy of methods to compensate for or accommodate their worse
      driving performance. CONCLUSION: Drivers with dementia are poorer drivers than
      cognitively normal drivers, but studies have not consistently demonstrated higher
      crash rates. Clinicians and policy makers must take these findings into account
      when addressing issues pertinent to drivers with a diagnosis of dementia.

PMID- 17537089
TI  - The combined effect of visual impairment and cognitive impairment on disability
      in older people.
AB  - OBJECTIVES: To determine the risk of disability in individuals with coexisting
      visual and cognitive impairment and to compare the magnitude of risk associated
      with visual impairment, cognitive impairment, or the multimorbidity. DESIGN:
      Prospective cohort. SETTING: North Carolina. PARTICIPANTS: Three thousand eight
      hundred seventy-eight participants in the North Carolina Established Populations
      for the Epidemiologic Studies of the Elderly with nonmissing visual status,
      cognitive status, and disability status data at baseline MEASUREMENTS: Short
      Portable Mental Status Questionnaire (cognitive impairment defined as > or =4
      errors), self reported visual acuity (visual impairment defined as inability to
      see well enough to recognize a friend across the street or to read newspaper
      print), demographic and health-related variables, disability status (activities
      of daily living (ADLs), instrumental activities of daily living (IADLs),
      mobility), death, and time to nursing home placement. RESULTS: Participants with
      coexisting visual and cognitive impairment were at greater risk of IADL
      disability (odds ratio (OR)=6.50, 95% confidence interval (CI)=4.34-9.75),
      mobility disability (OR=4.04, 95% CI=2.49-6.54), ADL disability (OR=2.84, 95%
      CI=1.87-4.32), and incident ADL disability (OR=3.66, 95%, CI=2.36-5.65). In each
      case, the estimated OR associated with the multimorbidity was greater than the
      estimated OR associated with visual or cognitive impairment alone, a pattern that
      was not observed for other adverse outcomes assessed. No significant interactions
      were observed between cognitive impairment and visual impairment as predictors of
      disability status. CONCLUSION: Individuals with coexisting visual impairment and
      cognitive impairment are at high risk of disability, with each condition
      contributing additively to disability risk. Further study is needed to improve
      functional trajectories in patients with this prevalent multimorbidity. When
      visual or cognitive impairment is present, efforts to maximize the other function
      may be beneficial.

PMID- 17537090
TI  - Stroke: a randomized trial of exercise or relaxation.
AB  - OBJECTIVES: To determine the feasibility and effect of exercise training after
      stroke. DESIGN: Randomized exploratory trial comparing exercise training
      (including progressive endurance and resistance training) with relaxation
      (attention control). SETTING: Interventions were performed in a rehabilitation
      hospital. PARTICIPANTS: Sixty-six independently ambulatory patients (mean age 72,
      36 men) without significant dysphasia, confusion, or medical contraindications to
      exercise training who had completed their usual rehabilitation and had been
      discharged from hospital. INTERVENTION: Both interventions were held three times
      a week for 12 weeks. Up to seven patients attended each session. MEASUREMENTS:
      The Functional Independence Measure; Nottingham Extended Activities of Daily
      Living; Rivermead Mobility Index; functional reach; sit-to-stand; elderly
      mobility score; timed up-and-go; Medical Outcomes Study 36-Item Short Form
      Questionnaire, version 2 (SF-36); Hospital Anxiety and Depression Score; aspects
      of physical fitness (comfortable walking speed, walking economy, and explosive
      leg extensor power) were measured at baseline, immediately after interventions (3
      months), and 7 months after baseline. RESULTS: The median number of intervention
      sessions attended was 36 (interquartile range (IQR) 30.00-36.75) for exercise and
      36 (IQR 30.50-37.00) for relaxation. Adherence to the individual exercises ranged
      from 94% to 99%. At 3 months, role-physical (an item in SF-36), timed up-and-go,
      and walking economy were significantly better in the exercise group (analysis of
      covariance). At 7 months, role-physical was the only significant difference
      between groups. CONCLUSION: Exercise training for ambulatory stroke patients was
      feasible and led to significantly greater benefits in aspects of physical
      function and perceived effect of physical health on daily life.

PMID- 17537091
TI  - Clinical factors associated with prescription of a prosthetic limb in elderly
      veterans.
AB  - OBJECTIVES: To determine how advanced age influences prosthetic prescription.
      DESIGN: Retrospective cohort analysis with theory-driven logistic regression
      models. A Post Amputation Quality-of-Life (PAQ) framework of outcomes was
      proposed and empirically tested. SETTING: Veterans Affairs Medical Centers.
      PARTICIPANTS: Two thousand three hundred seventy-five veterans with lower
      extremity amputations discharged between October 1, 2002, and September 30, 2003.
      MEASUREMENTS: Prosthetic prescription within 1 year of amputation. RESULTS:
      Patients younger than 76 were 4.5 times as likely to receive a prescription
      compared to those aged 86 and older (odds ratio=4.51, 95% confidence
      interval=1.36-14.99) after controlling for sex, marital status, living
      circumstance before hospitalization, anatomical level, etiologies, comorbidities,
      medical acuity, and initial functional status. Patients admitted from extended
      care and patients with peripheral vascular disease, systemic sepsis, renal
      failure, congestive heart failure, psychoses, metastatic cancer, paralysis, or
      other neurological disorders were less likely to receive a prescription, as were
      patients who underwent procedures for acute central nervous system disorders,
      severe renal disease, or serious nutritional compromise. Veterans evaluated
      initially as more cognitively and physically able had higher likelihood of
      prosthetic prescription, and those with transtibial amputations had higher
      likelihood of prosthetic prescription than those with transfemoral amputations.
      CONCLUSION: Amputees aged 75 and older are less likely to receive a prosthetic
      limb prescription than younger individuals, even after controlling for
      comorbidities and functional status. Findings support the PAQ framework, in which
      contexts, etiologies, anatomic level, comorbidities, medical acuity, and initial
      function are determinants of outcome. Medical and functional conditions that
      adversely affect level of energy, ability to move independently, or ability to
      exercise judgment reduce the likelihood of prosthetic prescription.

PMID- 17537092
TI  - Older age predicts short-term, serious events after syncope.
AB  - OBJECTIVES: To assess the relationship between age and 14-day serious events
      after an emergency department (ED) visit for syncope. DESIGN: One-year
      prospective cohort study. SETTING: Single academic ED. PARTICIPANTS: Adult
      patients with an ED complaint of syncope or near-syncope. MEASUREMENTS: Treating
      physicians prospectively recorded the presence or absence of potential risk
      factors for serious clinical events. Patients were contacted by telephone at 14
      days for a structured interview. A three-physician panel reviewed ED charts,
      hospital records, and telephone interview forms to identify predefined events.
      The primary outcome included any 14-day predefined event. A secondary outcome
      included any 14-day predefined event that was first diagnosed after the initial
      ED visit. Age was analyzed in 20-year intervals. Multivariate logistic regression
      controlled for baseline demographic, comorbidity, and electrocardiogram data.
      RESULTS: Of 592 eligible patients, 477 (81%) provided informed consent. Follow-up
      was successfully obtained for 463 (97%) patients. The age range was 18 to 96, and
      47% of patients were aged 60 and older. There were 80 (17%) patients who had a 14
      day event, including 18 (4%) with a delayed diagnosis. Compared with patients
      aged 18 to 39, the adjusted odds ratio (OR) of a serious outcome was 2.7 (95%
      confidence interval (CI)=0.9-8.4) for patient aged 40 to 59, 3.8 (95% CI=1.3-12)
      for patients aged 60 to 79, and 3.8 (95% CI=1.2-12) for patients aged 80 and
      older. CONCLUSION: Age of 60 and older is strongly associated with short-term
      serious events after an ED visit for syncope.

PMID- 17537093
TI  - Association between body mass index and mortality in an 80-year-old population.
AB  - OBJECTIVES: To evaluate the association between body mass index (BMI) and all
      cause mortality and cardiovascular disease (CVD) in an 80-year-old population.
      DESIGN: Cohort study. SETTING: Community-based. PARTICIPANTS: Six hundred ninety
      seven of 1,282 (54.4%) 80-year-old candidate individuals. MEASUREMENTS: The dates
      and causes of all deaths were followed up for 4 years. RESULTS: The relative
      hazard ratios (HRs) for all-cause mortality were lower in overweight subjects
      (BMI > or= 25.0) than in underweight (BMI<18.5) or normal-weight (BMI 18.5-24.9)
      subjects. Similarly, the HRs for mortality due to CVD in overweight subjects were
      78% less (HR=0.22, 95% confidence interval (CI)=0.06-0.77) than those in
      underweight subjects, and those in normal weight subjects were 78% less (HR=0.22,
      95% CI=0.08-0.60) than those in underweight subjects. Mortality due to CVD was
      4.6 times (HR 4.64, 95% CI=1.68-12.80) as high in underweight subjects as in
      normal-weight subjects, and mortality due to cancers was 88% lower (HR=0.12, 95%
      CI=0.02-0.78) in the overweight group than in the underweight group. There were
      no differences in mortality due to pneumonia. CONCLUSION: Overweight status was
      associated with longevity and underweight with short life, due to lower and
      higher mortality, respectively, from CVD and cancer.

PMID- 17537094
TI  - Coexisting cerebral infarction in Alzheimer's disease is associated with fast
      dementia progression: applying the National Institute for Neurological Disorders
      and Stroke/Association Internationale pour la Recherche et l'Enseignement en
      Neurosciences Neuroimaging Criteria in Alzheimer's Disease with Concomitant
      Cerebral Infarction.
AB  - OBJECTIVES: To determine whether patients with Alzheimer's disease (AD) and
      coexisting cerebral infarction (CI) that satisfy the National Institute for
      Neurological Disorders and Stroke/Association Internationale pour la Recherche et
      l'Enseignement en Neurosciences (NINDS-AIREN) neuroimaging criteria for vascular
      dementia (VaD) progress faster than those who do not satisfy the neuroimaging
      criteria. DESIGN: Retrospective cohort study. SETTING: Multidisciplinary memory
      clinic in a tertiary hospital. PARTICIPANTS: One hundred thirty consecutive
      patients with AD, with or without CI, followed up regularly for more than 1 year.
      MEASUREMENTS: The patients were classified according to the distribution and
      severity of CI as defined according to the NINDS-AIREN neuroimaging criteria into
      those with AD and no CI (AD-N), those with AD and CI not fulfilling neuroimaging
      criteria (AD-I), and those with AD and CI fulfilling neuroimaging criteria (AD
      V), and their differences in dementia progression were tested. The loss of
      independence, indicated by institution admission or a clinical dementia rating
      (CDR) score of 3, was defined as the endpoint for a poor outcome. RESULTS: The
      mean age was 75.8, and 68.5% were women. The initial Mini-Mental State
      Examination (MMSE) score was 15.3+/-0.4, and the average duration of follow up
      was 30.4 months. Fifty-four patients had reached study endpoint at the time of
      analysis. AD-V (hazard ratio (HR)=3.1, 95% confidence interval (CI)=1.2-8.2), use
      of psychotropic drugs (HR=2.7, 95% CI=1.1-6.4), and initial MMSE score (HR=0.9,
      95% CI=0.8-1.0) were independent predictors of poor outcome in the Cox regression
      model. CONCLUSION: In AD, co-occurrence of CI with distribution and severity as
      defined in the NINDS-AIREN neuroimaging criteria for VaD is associated with
      faster dementia progression.

PMID- 17537095
TI  - Emergence of rimantadine-resistant virus within 6 days of starting rimantadine
      prophylaxis with oseltamivir treatment of symptomatic cases.
AB  - OBJECTIVES: To report on the detection of rimantadine resistance within 6 days of
      starting rimantadine prophylaxis. DESIGN: Observational prospective study.
      SETTING: Fifty-bed nursing unit during the 2004/05 influenza season.
      PARTICIPANTS: All residents. INTERVENTION: Clinical monitoring for new onset of
      respiratory illness followed by collection of nasopharyngeal swabs for Directigen
      AB testing and influenza culture. After outbreak identification, rimantadine was
      administered as prophylaxis, whereas oseltamivir was used to treat symptomatic
      cases. Laboratory monitoring for the emergence of rimantadine resistance was
      reinitiated on the fifth day of rimantadine prophylaxis. MEASUREMENTS: Tabulation
      of respiratory illnesses, rapid tests and cultures yielding influenza A, and
      rimantadine sensitivity determination in five index isolates. RESULTS: A total of
      15 symptomatic cases were identified over 8 days. Amantadine sensitivity was
      determined in five cases. Three initial cases were sensitive to rimantadine,
      whereas two cases identified after 6 days of rimantadine prophylaxis were
      resistant to rimantadine. CONCLUSION: The Centers for Disease Control and
      Prevention reported that 91% of isolates collected early the following season
      (2005/06) were resistant to rimantadine. Rimantadine treatment is no longer
      recommended. This experience anticipated the new recommendations. If reemergence
      of sensitivity follows discontinuation of rimantadine use, using rimantadine as
      prophylaxis and oseltamivir for treatment of symptomatic cases might be
      efficacious and economical on a national scale.

PMID- 17537096
TI  - Medication review: patient selection and general practitioner's report of drug
      related problems and actions taken in elderly Australians.
AB  - OBJECTIVES: To investigate which patients general practitioners (GPs) selected
      for medication review based on risk factors for medication problems and patient
      demographics; to describe drug-related problems and actions taken to solve those
      problems during medication review consultations based on GPs' self-report.
      DESIGN: Cross-sectional. SETTING: General practices. PARTICIPANTS: Four hundred
      fifty-two patients recruited from 11 GPs. MEASUREMENTS: Patients' self-reported
      risk factors for medication misadventures collected from Medication Risk
      Assessment Forms; doctors' report of patients' drug-related problems and actions
      taken to solve those problems collected from Medication Review Checklists.
      Patients completed a Medication Risk Assessment Form in the waiting room, which
      they presented to their doctor, who then decided whether the patient needed a
      medication review. GPs completed a Medication Review Checklist. RESULTS: GPs
      completed 124 Medication Review Checklists. The group that had a medication
      review had a lower proportion of individuals aged 65 to 74 than the group that
      did not (40% vs 56%). The proportion of people with risk factors for medication
      misadventure was consistently higher for patients who received a medication
      review. GPs found that 88% (95% confidence interval (CI) =66-97) of patients who
      had a medication review had at least one problem with use of their medication.
      GPs reported taking at least one action for 104 (88%) patients (95% CI=65-97) to
      rectify medication problems. Most common actions taken were monitoring (55%),
      improving compliance (50%), dose change (37%), cessation of drug (28%), and
      ordering of a pathology test (26%). CONCLUSION: A Medication Risk Assessment Form
      completed by patients can be used to select patients for medication review, and
      medication reviews conducted by GPs can be beneficial in improving the use of
      medication in older people living in the community.

PMID- 17537097
TI  - Cumulative index of health deficiencies as a characteristic of long life.
AB  - OBJECTIVES: To describe the accumulation of aging-associated health disorders
      using a cumulative measure known as a frailty index (FI) and to evaluate its
      ability to differentiate long- and short-life phenotypes as well as the FI's
      connection to aging-associated processes in older people. DESIGN: Retrospective
      cross-sectional and longitudinal studies. SETTING: The National Long-Term Care
      Survey (NLTCS) data that assessed health and functioning of U.S. older
      individuals (> or =65) in 1982, 1984, 1989, 1994, and 1999 were analyzed. The
      NLTCS sample in each survey represents a mixture of longitudinal and cross
      sectional components. PARTICIPANTS: Approximately 5,000 individuals in each
      survey. MEASUREMENTS: A cumulative index of health and well-being deficiencies
      (disabilities, signs, diseases) was calculated as a count of deficits observed in
      an individual divided by the total number of all considered deficits. RESULTS:
      Men and women who died before the age of 75 and those who died after the age of
      85 exhibited remarkably similar FI frequency patterns despite the 10-year age
      difference between age profiles in these samples. Long life is consistently
      characterized in longitudinal analyses by lower FIs. FI dynamics are found to be
      strongly sex sensitive. CONCLUSION: The FI appears to be a sensitive age
      independent indicator of sex-specific physiological decline in aging individuals
      and a sex-specific discriminator of survival chances. The FI is a promising
      characteristic suitable for improving sex-sensitive forecasts of risks of adverse
      health outcomes in older people.

PMID- 17537098
TI  - Faculty development for the 21st century: lessons from the Society of General
      Internal Medicine-Hartford Collaborative Centers for the Care of Older Adults.
AB  - In this review of a recent set of faculty development initiatives to promote
      geriatrics teaching by general internists, nontraditional strategies to promote
      sustained change were identified, included enrolling a limited number of "star"
      faculty, creating ongoing working relationships between faculty, and developing
      projects for clinical or education program improvement. External funding,
      although limited, garnered administration support and was associated with changes
      in individual career trajectories. Activities to enfranchise top leadership were
      felt essential to sustain change. Traditional faculty development programs for
      clinician educators are periodic, seminar-based interventions to enhance teaching
      and clinical skills. In 2003/04 the Collaborative Centers for Research and
      Education in the Care of Older Adults were funded by the John A. Hartford
      Foundation and administered by the Society of General Internal Medicine. Ten
      academic medical centers received individual grants of $91,000, with required
      cost sharing, to develop collaborations between general internists and
      geriatricians to create sustained change in geriatrics clinical teaching and
      learning. Through written and structured telephone surveys, activities designed
      to foster sustainability at funded sites were identified, and the activities and
      perceived effects of funding at the 10 funded sites were compared with those of
      the 11 highest-ranking unfunded sites. The experience of the Collaborative
      Centers supports the conclusion that modest, targeted funding can provide the
      credibility and legitimacy crucial for clinician educators to allocate time and
      energy in new directions. Key success factors likely include high intensity and
      duration, integration into career trajectories, integration into clinical
      programs, and activities to enfranchise institutional leadership.

PMID- 17537099
TI  - White coats meet grey power: students and seniors respond to an
      "intergenerational gala".
AB  - Research suggests that nonclinical interactions with older people may enhance
      medical students' traditionally poor attitudes toward this patient group.
      Although extensive literature has reported on student attitudes, seniors'
      perspectives of their relationships with younger healthcare professionals (HCPs)
      are generally unknown. This study explores students' and seniors' perceptions of
      aging and the influence of these perceptions on medical practice before and after
      a recreational, intergenerational event. In March 2006, the Schulich Faculty of
      Medicine and Dentistry at the University of Western Ontario held its second
      annual "Intergenerational Gala." Approximately 150 seniors and students were
      invited to complete a brief pre- and postevent questionnaire exploring attitudes
      toward aging, care of older people, and HCP training. After the event,
      approximately 60% of students did not feel that their curriculum contained
      adequate geriatrics content, and more than one-third of seniors did not feel that
      today's HCPs are adequately trained to address the healthcare needs of older
      people. Content analysis indicated strongly positive postevent perceptions of the
      gala but also considerable divergences between students' and seniors' responses
      to "To me, growing older means. ..." Seniors also offered advice to young HCPs
      encouraging listening, patience, and not using "age" as a medical diagnosis. The
      second Intergenerational Gala explored similarities and differences between how
      seniors and students view aging. Although significant changes in attitudes were
      not observed, qualitative responses from both groups suggest that similar events
      hold promise as part of a concerted curricular strategy to encourage and improve
      intergenerational relations in the context of medical practice.

PMID- 17537100
TI  - Differential mini-mental state examination profiles of older people with diabetes
      mellitus with early Alzheimer's disease.

PMID- 17537101
TI  - Association between vitamin B6 and white matter hyperintensities in patients with
      Alzheimer's disease not mediated by homocysteine metabolism.

PMID- 17537102
TI  - Cost of medication requirement during radiotherapy: implications for an elderly
      oncological population.

PMID- 17537103
TI  - Can hip protector use cost-effectively prevent fractures in community-dwelling
      geriatric patients?

PMID- 17537106
TI  - Dysphagia and enlarged thoracic aortic aneurysm: is there ever a causal
      relationship?

PMID- 17537107
TI  - Uncovering the hemodynamic profiles of patients with orthostatic hypotension.

PMID- 17537108
TI  - Hepatocyte growth factor and visfatin in elderly bedridden patients.

PMID- 17537109
TI  - Lethal fecaloma.

PMID- 17537110
TI  - The assessment of physical activity in inpatient rehabilitation-an important
      aspect of the identification of frailty in hospitalized older people.

PMID- 17537114
TI  - Regulation and guidance of cell behavior for tissue regeneration via the siRNA
      mechanism.
AB  - RNA intereference and short-interfering RNA (siRNA) have been proven to be
      effective at decreasing the expression of target genes and provide a valuable
      tool for promoting and directing the growth of functional tissues for repair and
      reconstructive tissue engineering applications. siRNA is a gene-silencing
      mechanism that involves double-stranded RNA-mediated sequence-specific mRNA
      degradation and is a powerful mechanism for controlling cell behavior. The use of
      siRNA to reduce the expression of a target gene can induce the expression of one
      or more tissue-inductive factors, direct the differentiation of stem or
      progenitor cells, or remove a factor that inhibits regeneration, which can be
      useful in fundamental studies of tissue formation or in applications to promote
      in vivo regeneration. The potential of siRNA is illustrated through specific
      examples within the fields of angiogenesis, bone and nerve regeneration, and
      wound healing. In addition, challenges to deliver siRNA effectively for tissue
      engineering applications are addressed. siRNA represents a powerful tool to
      investigate and/or promote tissue formation, and numerous opportunities exist for
      identifying targets that promote regeneration of tissue and developing effective
      delivery systems.

PMID- 17537115
TI  - Negative pressure therapy is effective to manage a variety of wounds in infants
      and children.
AB  - Negative pressure therapy (NPT) has been accepted as a valuable adjunct for wound
      closure in adults; however, reports on its effectiveness in young children and
      infants, including neonates, are limited. A retrospective chart review was
      conducted on children treated with NPT at a single institution between January
      2003 and December 2005. Wound volumetric measurements were calculated at the
      start and end of therapy. Sixty-eight patients with 82 wounds were identified.
      The mean age was 8.5 years (range 7 days-18 years). Twenty patients (29%) were 2
      years of age or younger, including eight neonates. Wound types included: pressure
      ulcers (n=13), extremity wounds (n=18), dehisced surgical wounds (n=19), open
      sternal wounds (n=10), wounds with fistulas (n=3), and complex abdominal wall
      defects (n=6). Low suction pressures (<100 mmHg) were generally used in children
      younger than 4 years of age. Following NPT, 93% of wounds decreased in volume.
      The average wound volume decrease was 80% (p<0.01, n=56). NPT can be effectively
      used to manage a variety of wounds in children and neonates. No major
      complications were identified in our retrospective review. Prospective studies
      are required to better refine the use of this technology in children.

PMID- 17537116
TI  - Preferences of patients, doctors, and nurses regarding wound dressing
      characteristics: a conjoint analysis.
AB  - The different choices doctors, nurses, and patients make regarding wound dressing
      materials are generally based on personal preferences, because strong evidence
      and guidelines on local wound care for open wounds are lacking. We studied which
      attributes of a wound dressing doctors, nurses, and patients consider the most
      important. A conjoint analysis questionnaire comprising paper-based descriptions
      with six attributes, and questions regarding the willingness-to-pay for these
      attributes were sent out to surgical patients, (assistant)-surgeons and nurses.
      Preferences for wound dressing attributes were similar for doctors (n=50), nurses
      (n=150), and patients (n=74). Pain during dressing changes, duration of
      hospitalization, and wound healing time were ranked highest. Doctors would spend
      more money on a shorter hospitalization, nurses on pain reduction, and patients
      on quicker wound healing. Patients were willing to pay a relatively small monthly
      amount out of pocket for a dressing that would result in a quicker and less
      painful wound healing. Doctors, nurses, and patients prefer similar attributes of
      wound dressing materials, but differ in their willingness-to-pay. To achieve a
      more consistent local wound care, clinical decision-making should be in
      accordance with these preferences. These should also be the focus for
      manufacturers and researchers to obtain more evidence on which materials best
      match these attributes.

PMID- 17537117
TI  - Treatment of recalcitrant venous leg ulcers with autologous keratinocytes in
      fibrin sealant: a multinational randomized controlled clinical trial.
AB  - In a multicenter trial, the effect of a commercially available combination of
      autologous keratinocytes (3-6 x 10(6)/mL) with fibrin sealant (Tissucol Duo S
      Immuno, Baxter Hyland Immuno) on the healing of recalcitrant venous leg ulcers
      (duration >3 months) was compared with standard care. The primary endpoint was
      time to healing, and the secondary endpoint was number of healed ulcers in both
      groups. Both groups received compression therapy with short-stretch bandages.
      Forty-four (38.3%) of the 116 patients who had BioSeed-S treatment achieved
      complete healing of the target ulcer compared with 24 (22.4%) of 109 patients who
      received standard treatment. The advantage for treatment with BioSeed-S over
      standard treatment was statistically significant (chi-square test: p=0.0106).
      Time to complete healing of ulcers: the log-rank test for equality over strata
      revealed a superiority of treatment with BioSeed-S+compression (median: 176 days)
      over compression+standard care (median >201 days) (p<0.0001). This study, to date
      the largest multicenter study with autologous keratinocytes, provides evidence
      for its efficacy in the treatment of patients with therapy-resistant chronic
      venous leg ulcers.

PMID- 17537118
TI  - Surgical wound-healing complications in heart transplant recipients treated with
      rapamycin.
AB  - The aim of this retrospective analysis was to assess the influence of rapamycin
      (RAPA) used perioperatively on surgical complications in heart transplant
      recipients. The study group consisted of 28 heart transplant recipients (26M/2F,
      49.2+/-11 years) receiving 15 mg of RAPA before operation, 10 mg of RAPA on the
      first postoperative day (POD) and 5 mg daily (n=20) thereafter, or 5 mg daily
      starting on POD 2 (n=8), until the introduction of cyclosporine-A. A matched
      historical control group was composed of 28 patients (26M/2F, 49.7+/-9 years)
      receiving cyclosporine-A from POD 1. We compared a number of surgical
      complications and reinterventions among groups. Statistical significance was
      assessed using the chi-square test and the Mann-Whitney U-test. There were 16
      (57%) patients in the study group vs. six (21%) in the control group requiring
      reintervention (p=0.014). Pericardial tamponade decompression was performed in
      seven (25%) vs. zero patients, and sternum refixation in seven (25%) vs. zero
      patients (p=0.015). None of the wounds was infected. The overall drainage volume
      was 4,213+/-5,996 vs. 1,911+/-1,728 mL (p=NS). The frequencies of biopsy-proven
      rejection and infection were comparable, except lower cytomegalovirus infection
      rates in the study group: three (11%) vs. 11 (39%) for the control group
      (p=0.023). The use of RAPA in the perioperative period of heart transplantation
      increases the risk of surgical wound-healing complications.

PMID- 17537119
TI  - Factors influencing the outcome of lower-extremity diabetic ulcers treated with
      hyperbaric oxygen therapy.
AB  - The objectives of this study were to report outcomes of a large number of
      patients receiving hyperbaric oxygen therapy (HBO(2)T) for diabetic lower
      extremity ulcers, and to identify likely outcome predictors. Five hyperbaric
      facilities supplied data on 1,006 patients. A sixth clinic served as a validation
      sample for the regression-based prediction model, and later additional data from
      Memorial Hermann Hospital were added. The severity of lower-extremity lesions was
      assessed upon initiation of HBO(2)T using the Modified Wagner scale, and the
      outcome described as healed, partially healed, not improved, amputated, or died.
      Overall, 73.8% of patients improved (granulated or healed). Factors significantly
      related to outcome included renal failure, pack-year smoking history,
      transcutaneous oximetry, number of HBO(2)T treatments, and interruption of
      treatment regimen. Number of treatments per week and treatment pressure (2.0 vs.
      2.4 atmospheres absolute) were not significant factors in outcome. Concomitant
      administration of autologous growth factor gel did not improve outcome. A
      multiple regression model was fitted to the data that can be used to predict the
      outcome of diabetic patients undergoing HBO(2)T. Given the high cost of
      amputation and rehabilitation, these data suggest that hyperbaric oxygen
      treatment should be an important adjunctive therapy to heal lower-extremity
      lesions, especially those with a Wagner grade of 3 or higher.

PMID- 17537120
TI  - Clinical utilization of near-infrared spectroscopy devices for burn depth
      assessment.
AB  - The diagnosis of burn depth is based on a visual assessment and can be
      subjective. Near-infrared (NIR) spectroscopic devices were used preclinically
      with positive results. The purpose of this study was to test the devices in a
      clinical setting using easily identifiable burn wounds. Adult patients with acute
      superficial and full-thickness burns were enrolled. NIR point spectroscopy and
      imaging devices were used to collect hemodynamic data from the burn site and an
      adjacent unburned control site. Oxy-hemoglobin and deoxy-hemoglobin
      concentrations were extracted from spectroscopic data and reported as oxygen
      saturation and total hemoglobin. Sixteen patients (n=16) were included in the
      study with equal numbers in both burn wound groups. Point spectroscopy data
      showed an increase in oxygen saturation (p<0.0095) and total hemoglobin (<0.0001)
      in comparison with the respective control areas for superficial burn wounds. The
      opposite was true for full-thickness burns, which showed a decrease in
      oxygenation (p<0.0001) and total hemoglobin (p<0.0147) in comparison with control
      areas. NIR imaging technology provides an estimate of hemodynamic parameters and
      could easily distinguish superficial and full-thickness burn wounds. These
      results confirm that NIR devices can successfully distinguish superficial and
      full-thickness burn injuries.

PMID- 17537121
TI  - Alteration of Smad3 signaling in ischemic rabbit dermal ulcer wounds.
AB  - Impaired reepithelialization is a hallmark of chronic, ischemic wounds; however,
      the pathogenesis of the delayed reepithelialization in these wounds remains
      poorly understood. Transforming growth factor beta is involved in both the normal
      and hypoxic wound-healing response and exogenous overexpression of Smad3, which
      has been known to accelerate reepithelialization. Recently, it was shown in the
      rabbit ear dermal ulcer model that Ad-Smad3 injection enhanced
      reepithelialization and granulation tissue formation suggesting a positive effect
      of Smad3 on wound healing. However, little is known about the role of Smad3 in
      the ischemic wound healing process. In this study, we examined the effect of
      Smad3 in an ischemic wound model. Ad-Smad3 or Ad-LacZ (10(8) pfu/wound) was
      injected into either ear of white New Zealand rabbits. Twenty-four hours later,
      these ears were rendered ischemic using an established model, and four 7 mm full
      thickness punch wounds were made on each ear. Histological evaluation showed a
      significant increase in reepithelialization parameters in Ad-Smad3-transfected
      wounds (p<0.01). In contrast, granulation tissue parameters were not affected by
      Smad3 in ischemia. Smad4 and Smad7 mRNA-expression was not affected by Smad3
      overexpression. Connective tissue growth factor protein was up-regulated under
      ischemic conditions but was unaffected by Smad3 transfection in both ischemic and
      nonischemic wounds. Our results suggest an enhancing effect of Smad3 on
      reepithelialization in an ischemic wound model that, in turn, might provide novel
      therapeutic options. Furthermore, the lack of alteration of Smad-dependent
      intermediates by Smad3 overexpression suggests the activation of Smad-independent
      pathways in ischemia.

PMID- 17537122
TI  - Enhanced epithelial gap closure and increased angiogenesis in wounds of diabetic
      mice treated with adult murine bone marrow stromal progenitor cells.
AB  - The direct application of bone marrow (BM) can accelerate the healing of chronic
      wounds. We hypothesized that this effect is due to the presence of stromal
      progenitor cells (SPCs) found within whole BM preparations. To test this
      hypothesis, we isolated adult murine SPCs from whole BM and examined their
      ability to enhance impaired wound healing compared with ficoll separated BM cells
      in the diabetic (db/db) mouse model. SPCs significantly enhanced
      reepithelialization, granulation tissue formation, and neovascularization
      compared with control wounds treated with BM or PBS alone. Higher frequencies of
      donor SPC cells compared with donor BM cells were observed in treated wounds at 7
      days. Transdifferentiation into GFP-positive mature endothelial cells was not
      observed. These observations suggest that SPCs improve wound healing through
      indirect mechanisms which lead to enhanced vascularization rather than through
      direct participation and incorporation into tissue. We conclude that topical
      application of BM-derived SPCs may represent an effective strategy for the
      treatment of chronic diabetic wounds.

PMID- 17537123
TI  - Fibrin-embedded administration of VEGF plasmid enhances skin flap survival.
AB  - The aim of the present study was to experimentally evaluate whether topical
      fibrin-mediated administration of a vascular endothelial growth factor (VEGF)-A
      plasmid to the wound bed can protect skin flaps from necrosis. A plasmid
      expression vector containing the VEGF-A cDNA was constructed. The plasmid was
      then administered to the wound bed of rat abdominal skin flaps in a fibrin
      sealant. The percentage of viable, ischemic and necrotic tissue was assessed
      postoperatively as a baseline and after 3 and 7 days using digital surface area
      morphometry. Laser Doppler imaging of the flaps and VEGF-A Western blot analysis
      of flap tissue were performed to assess angiogenesis and VEGF-A tissue levels.
      Flaps treated with VEGF plasmids in the presence of uptake enhancing
      Lipofectamine transfection reagent increased flap survival 7 days postoperatively
      significantly associated with markedly elevated tissue perfusion and enhanced
      tissue VEGF-A protein expression. Our results indicate that topical fibrin
      mediated administration of a VEGF-A plasmid may serve as an alternative to
      previous strategies in treating ischemic skin flaps. The suggested therapeutic
      approach is easily applicable and inexpensive in preparation. Thus, this protocol
      may also enhance wound healing in posttrauma skin lacerations or in skin grafts.

PMID- 17537124
TI  - Efficacy of gaseous nitric oxide in the treatment of skin and soft tissue
      infections.
AB  - Bacterial burden significantly interferes with the healing process in chronic
      ulcers. Nitric oxide (NO) plays a key role in regulating skin's response to
      infection and wound healing. In previous studies, we demonstrated that exogenous
      NO gas (gNO) at 200 parts per million (ppm) exhibits potent antimicrobial effects
      against a representative range of pathogens. The aim of the present study is to
      explore the antimicrobial properties of gNO in vivo and to determine skin cells'
      sensitivity to the cytotoxic effects of gNO. To test gNO's antimicrobial effects,
      full-thickness wounds were infected with Staphylococcus aureus on the dorsal skin
      surface of New Zealand White rabbit and treated with 200 ppm gNO for 8 hours/day
      for 3 consecutive days. Significant reduction in wound bacterial content was
      observed in the presence of gNO. In a separate experiment, primary cultures of
      human fibroblasts, keratinocytes, and endothelial cells were established to test
      gNO's cytotoxicity in the skin. Methyl thiazolyl tetrazolium proliferation assays
      demonstrated that human skin cells, unlike bacterial cells, exhibited significant
      resistance toward gNO cytotoxicity. In vitro migration studies on keratinocytes
      and endothelial cells revealed that gNO treatment does not seem to interfere with
      reepithelialization and angiogenesis during the process of wound healing.
      Following 24 hours of gNO treatment, fibroblasts expressed significantly higher
      levels of procollagen and, to a lesser degree, a decrease in matrix
      metalloproteinase -1 mRNA. In conclusion, the present study provides evidence for
      the potential application of high doses of gNO as an antimicrobial agent for the
      treatment of infection in chronic nonhealing ulcers or burn patients, without
      compromising the viability, and function of skin cells.

PMID- 17537125
TI  - Basic fibroblast growth factor in an artificial dermis promotes apoptosis and
      inhibits expression of alpha-smooth muscle actin, leading to reduction of wound
      contraction.
AB  - To clarify the mechanisms underlying declines in wound contraction caused by
      basic fibroblast growth factor (bFGF) and the role of autologous fibroblasts in
      modulating wound healing, we have examined the expression of alpha-smooth muscle
      actin (alpha-SMA) and apoptosis in a model of wound healing using collagen
      sponges with and without bFGF (1 microg) and/or fibroblasts (1 x 10(6)
      cells/cm(2)) applied to experimentally produced full-thickness skin wounds in
      rats (n=10 for each group). At 7 days postoperatively, wounds filled with a
      fibroblast-seeded collagen sponge (fibroblast-seeded group) displayed a greater
      area of collagen sponge and a smaller area of fibroblasts compared with control
      wounds filled with collagen sponge alone (control group). Therefore, seeding of
      fibroblasts in the dermal substitute might retard degradation of the collagen
      sponge, inhibiting fibroblast infiltration into the substitute. By day 14, wounds
      filled with bFGF-treated collagen sponge without fibroblast seeding (bFGF group)
      displayed decreased alpha-SMA expression and significantly increased apoptosis
      compared with other wounds. Double staining revealed that apoptosis in alpha-SMA
      positive fibroblastic cells was significantly increased in the bFGF group,
      suggesting that bFGF treatment is a potent stimulator of myofibroblast apoptosis.
      Furthermore, morphometric analysis demonstrated the significant decrease in the
      level of wound contraction and the degree of mature collagen bundle formation in
      the bFGF group by day 42. The bFGF group also showed increased bFGF expression in
      macrophages by day 28. These results suggest that bFGF administration to an
      artificial dermis promotes apoptosis of alpha-SMA-positive fibroblastic cells and
      inhibits alpha-SMA expression in the treated wound, thus reducing wound
      contraction.

PMID- 17537126
TI  - Differential regulation of free-floating collagen gel contraction by human fetal
      and adult dermal fibroblasts in response to prostaglandin E2 mediated by an
      EP2/cAMP-dependent mechanism.
AB  - In contrast to fetal wound healing, dermal adult wound healing results in
      imperfect repair and scar formation. Fibroblasts are responsible for the
      contraction and remodeling of the wound matrix, which is influenced by
      inflammatory mediators including prostaglandin E2 (PGE2). This study addresses
      the mechanism by which PGE2 regulates contraction of collagen gels by human fetal
      and adult dermal fibroblasts. We hypothesized that the intrinsic phenotypic
      properties of the two types of fibroblasts and their responses to PGE2 alter
      their contraction properties and contribute to different wound healing outcomes.
      Contraction was evaluated using free-floating fibroblast-populated collagen gels
      that contract by migratory forces. PGE2 was found to differentially inhibit
      collagen gel contraction by fetal and adult fibroblasts. This effect was mimicked
      by a specific PGE2 receptor agonist as well as by two pharmacological agents,
      indicating a cyclic adenosine monophosphate-dependent signaling pathway mediated
      through the EP2 receptor. Our results indicate that fetal fibroblast contraction
      is maintained by a more stable actin cytoskeleton. Therefore, the migratory
      phenotype may be sufficient for physical remodeling of the wound matrix leading
      to regenerative repair. Maintenance of this phenotype in the later stages of
      wound healing could potentially be achieved by targeting cyclic adenosine
      monophosphate via the EP2 receptor.

PMID- 17537127
TI  - Antibacterial activity of positive and negative polarity low-voltage pulsed
      current (LVPC) on six typical Gram-positive and Gram-negative bacterial pathogens
      of chronic wounds.
AB  - The positive effect of electrical stimulation (ES) on wound healing has been
      shown in vitro and in vivo. On the basis of increased blood flow, protein
      denaturation, and stimulation of cellular defense, an antibacterial effect of ES
      is to be expected. Although the antibacterial effect of ES already has been
      demonstrated in vitro, little attention has been paid to the direct antibacterial
      effect of changing polarity of the applied current. The aim of this study was to
      investigate the antibacterial effect of positive and negative monophasic low
      voltage pulsed current on typical Gram-positive and Gram-negative pathogens of
      chronic wounds. Using the Dermapulse-System, three Gram-negative (Escherichia
      coli, Pseudomonas aeruginosa, Klebsiella pneumoniae) and three Gram-positive
      (Staphylococcus aureus, Staphylococcus epidermidis, Escherichia faecium)
      organisms were tested against positive and negative polarity low voltage pulsed
      current. All tested organisms were significantly reduced by ES. The reduction
      differed significantly between positive polarity and control and negative
      polarity and control, with the highest log10 reduction factor (RF) achieved with
      positive polarity. Using positive polarity, the maximum RF was measured for E.
      coli (median log10 RF 0.83; 25th percentile 0.59, 75th percentile 0.98) and the
      lowest for S. epidermidis (median log10 RF 0.20; 25th percentile 0.17, 75th
      percentile 0.24). Yet, there was no significant difference with positive ES
      against Gram-positive or Gram-negative organisms.

PMID- 17537128
TI  - Cbfa1/Runx2-deficiency delays bone wound healing and locally delivered
      Cbfa1/Runx2 promotes bone repair in animal models.
AB  - Core binding factor 1 (Cbfa1)/runt-related transcription factor 2 (Runx2) has
      been identified as a "master gene" in osteoblastic differentiation. In this two
      part study, part I of the study was undertaken to test the hypothesis that bone
      regeneration is compromised in Cbfa1+/- mice. Compared with wild-type mice, wound
      healing was dramatically delayed in Cbfa1+/- mice characterized by the presence
      of a small amount of bone near the base of the wounds. The bone defects were
      largely filled with fibrous connective tissues 3 weeks after surgery. Part II was
      performed to determine the effects of Cbfa1 in enhancing bone wound healing using
      a gene-activated matrix (GAM) method. Cbfa1 cDNA was mixed with a biodegradable
      bovine type I collagen sponge and was inserted into the periodontal window wounds
      of mice. Control sponges were collagen matrix without Cbfa1 cDNA. Histological
      analysis and immunohistochemical staining demonstrated that compared with
      controls, there was increased new bone formation that almost filled the wound
      defects 14 days after surgery in the Cbfa1-GAM group. The collagen sponge matrix
      did not seem to elicit significant foreign body reaction in either group. In
      conclusion, the reduced expression of Cbfa1 interferes with the process of bone
      wound healing, and local application of Cbfa1 cDNA incorporated into a collagen
      matrix promotes bone tissue regeneration.

PMID- 17537129
TI  - Inhibition of osteogenic differentiation of human mesenchymal stem cells.
AB  - Mesenchymal stem cells (hMSCs) have been shown to differentiate into osteoblasts
      that, in turn, are capable of forming tissues analogous to bone. The present
      study was designed to investigate the inhibition of osteogenesis by hMSCs. Bone
      marrow-derived hMSCs were treated with transforming growth factor beta-3
      (TGFbeta3) at various doses during or after their differentiation into osteogenic
      cells. TGFbeta3 was encapsulated in poly(DL-lactic-co-glycolic acid) (PLGA)
      microspheres and released via controlled delivery in the osteogenic culture of
      hMSCs and hMSC-derived osteoblasts for up to 28 days. Controlled release of
      TGFbeta3 inhibited the osteogenic differentiation of hMSCs, as evidenced by
      significantly reduced alkaline phosphatase activity and staining, as well as
      decreased mineral deposition. After hMSCs had been differentiated into
      osteoblasts, controlled release of TGFbeta3 further inhibited not only alkaline
      phosphatase and mineral deposition but also osteocalcin expression. These
      findings demonstrate the potential for sustained modulation of the behavior of
      stem cells and/or stem cell-derived lineage-specific cells via controlled release
      of growth factor(s). The attenuation of osteogenic differentiation of MSCs may
      facilitate understanding not only the regulation and patterning of osteogenesis
      in development but also several pathological models such as osteopetrosis,
      craniosynostosis, and heart valve calcification.

PMID- 17537130
TI  - Adult rat hepatic bipotent progenitor cells remain dormant even after extensive
      hepatectomy.
AB  - S It remains unknown whether the normal adult liver contains bipotent
      stem/progenitor cells, and if it does, then what are the circumstances under
      which they proliferate. The aim of this study was to clarify whether the normal
      adult liver contains hepatic stem/progenitor cells, and if it does, will they be
      activated by extensive hepatectomy? Adult rat liver cells were isolated and
      cultured at a low-density, and the colony-forming assay was performed to evaluate
      the cell proliferative capacity. Immunocytochemistry and reverse transcription
      polymerase chain reaction were used to investigate the multilineage
      differentiation capability. The rate of colony formation by cells from the normal
      liver and those from the regenerating liver after partial hepatectomy (PH) were
      compared to determine whether progenitor cell proliferation might be activated by
      PH. Only a few epithelial colonies (0.043+/-0.009% of nonparenchymal cells)
      continued to proliferate for more than 1 month. Reverse transcription-polymerase
      chain reaction and immnocytochemistry showed that these progenitor colonies
      expressed both hepatocyte and cholangiocyte markers. The proportion of progenitor
      cells that formed bipotential colonies did not differ significantly between the
      cells obtained from the normal and PH livers. Adult normal liver contains
      bipotent hepatic progenitor cells, but they are scarcely activated even after
      extensive hepatectomy.

PMID- 17537134
TI  - "Blind man dermatology" revisited.

PMID- 17537135
TI  - Understanding clinical trial outcomes: design, analysis, and interpretation.
AB  - Outcomes (a variable intended for comparison between groups) are integral to the
      design, conduct, and data analysis of a clinical trial. They are broadly divided
      into four categories: physician based, patient reported, economic based, and
      technology based. Each is used in dermatology to some degree, but no consensus
      exists as to what type of outcome or degree of validation should be employed.
      This is problematical because poor quality outcomes or their incorrect use may
      invalidate the results of a clinical trial. Despite their importance, outcome
      measures in dermatology receive little attention. The present authors aim to
      provide an overview of important considerations for outcome measures and a
      practical approach to their analysis.

PMID- 17537136
TI  - Ultrasound as an outcome measure to assess disease activity in disorders of skin
      thickening: an example of the use of radiologic techniques to assess skin
      disease.
AB  - Good outcome measures are required to determine whether a therapy is effective,
      both in routine clinical practice and in experimental clinical trials. In
      disorders of skin thickening such as morphea and scleroderma, more commonly used
      outcome measures that use a subjective score based on palpated skin thickening
      are fraught with error. By contrast, measurements made by ultrasound have great
      promise as outcome measures that are quantitative, valid, reproducible, and
      responsive. Further studies should establish its role in the field. In this
      paper, the present authors used ultrasound to illustrate the criteria that are
      required to establish a technology-based outcome measure.

PMID- 17537137
TI  - Development of the CLASI as an outcome instrument for cutaneous lupus
      erythematosus.
AB  - Skin involvement is a frequent presenting manifestation of systemic lupus
      erythematosus (SLE). Cutaneous lupus erythematosus (CLE), frequently occurring
      without SLE, may be even more common than SLE. Until recently, clinical
      instruments to measure skin involvement in CLE did not exist, hampering clinical
      research in this field. In this paper the present authors describe outcome
      instruments for SLE and outline the considerations underlying the design and
      validation of an outcome instrument for CLE, the cutaneous lupus disease area and
      severity index. These studies serve as a model for development and validation of
      standardized instruments that can be applied to other cutaneous diseases,
      particularly autoimmune diseases, in order to facilitate epidemiologic studies
      and clinical trials.

PMID- 17537138
TI  - Patient preference quality of life measures in dermatology.
AB  - Patient quality of life (QOL) is an important aspect of health care. It is
      crucial that we continue to develop instruments to assist in detecting burden of
      disease, interpreting outcomes of clinical trials, determining cost effectiveness
      of therapies, and guiding clinical decision making. The measurement of patient
      preferences, specifically utilities and contingent valuation, for health states
      provides data that can assist in the aforementioned endeavors. Patient
      preferences have been measured in many areas of medicine. However, it is
      relatively new to the field of dermatology. The present authors provide an
      overview of the basic concepts of patient preference measures and how they
      compare to the widely used health status instruments. Various techniques that
      have been used to elicit patient preferences are discussed, including standard
      gamble, time trade-off, willingness-to-pay, rating scales, health utilities
      index, and EuroQol (EQ-5D). In addition, the present authors review the current
      literature reporting utilities relevant to dermatology.

PMID- 17537139
TI  - Does cost-effectiveness play a role in clinical trials?
AB  - Cost is a measure of resources consumed. By assessing costs, pharmacoeconomic
      studies complement studies of efficacy and safety, helping to determine the
      relationships of treatment and outcome. Costs are divided into three categories,
      including direct cost (resources attributable to the intervention), indirect cost
      (resulting from reduced productivity), and intangible cost (incurred from pain
      and emotional suffering). Insurance companies, patients, doctors, and the society
      all have different perspectives with respect to costs. The present authors review
      different types of cost analyses and their use in studies of psoriasis, atopic
      dermatitis, and basal cell carcinoma treatment. Cost studies influence
      clinicians, policy makers, and third-party payers' decisions regarding the
      implementation of particular therapies or programs. Collection of cost data needs
      to be incorporated into clinical trials to facilitate these decisions.

PMID- 17537141
TI  - Jung and White and the God of terrible double aspect.
AB  - This paper discusses theoretical, historical and personal issues in the ill-fated
      friendship and intellectual collaboration between C.G. Jung and the Dominican
      scholar Victor White, O.P., based on primary documents in their correspondence,
      1945 to 1960. The collaboration of Jung and White began with high expectations
      but fell into painful disagreements about the nature of God, the problem of evil,
      and shadow aspects of the Self. They made a rapid commitment to their working
      alliance based on personal and professional hopes, but paying scant attention to
      their divergent underlying assumptions. White hoped to build theoretical and
      practical connections between Jungian psychology and Catholic theology for the
      sake of modern Catholics. Jung needed learned theological support as he explored
      the psychological meanings of Christian symbols, including the central symbol of
      Christ. At the grandest level, they both hoped to transform the Christian West,
      after the moral disaster of World War II. Their collaboration was risky for both
      men, especially for White in his career as a Dominican, and it led to
      considerable suffering. The Self is prominent in the relationship, symbolically
      present in the text of the correspondence and consciously forming their major
      topic of debate. From the start, the Self is an archetypal field, drawing the
      friends into their visionary task at the risk of unconscious inflation. Later the
      Self is revealed with its shadow as a burden, a puzzle, and a basis for
      estrangement. Finally, with the intervention of feminine wisdom, mortal suffering
      is transformed by an attitude of conscious sacrifice.

PMID- 17537142
TI  - The Jung-White dialogue and why it couldn't work and won't go away.
AB  - White's Thomism and its Aristotelian foundation were at the heart of his
      differences with Jung over the fifteen years of their dialogue. The paper
      examines the precedents and consequences of the imposition of Thomism on the
      Catholic Church in 1879 in order to clarify the presuppositions White carried
      into his dialogue with Jung. It then selects two of Jung's major letters to White
      to show how their dialogue influenced Jung's later substantial work, especially
      his Answer to Job. The dialogue with White contributed to foundational elements
      in the older Jung's development of his myth which simply outstripped White's
      theological imagination and continues to challenge the worlds of contemporary
      monotheistic orthodoxy in all their variants.

PMID- 17537143
TI  - Of texts and contexts: reflections upon the publication of The Jung-White
      Letters.
AB  - In addition to his many other personae, Jung was a writer and an author, which
      means a creator, whose written works underlie and authorize a field of thought
      and clinical work, i.e., analytical psychology. Not widely recognized is that
      many of his authored texts were stimulated by important and intense personal
      relationships. Freud and Victor White loom large, the first standing behind major
      early analytical texts like Wandlungen und Symbole der Libido and Psychological
      Types, the second behind later texts on culture, religion, and Christian
      theology. The publication of The Jung-White Letters reveals the significance of
      his relationship with Victor White for the authoring of Answer to Job.

PMID- 17537144
TI  - Jung and Kabbalah: imaginal and noetic aspects.
AB  - Jung made use of kabbalistic images and motifs in various parts of his opus,
      including in his alchemical studies, in Aion, and extensively in Mysterium
      Coniunctionis. He also recorded an important dream after his heart attack which
      made use of kabbalistic symbolism in Memories, Dreams, Reflections. In this paper
      I explore Jung's ideas in relation to Kabbalah, first, by differentiating between
      Jung's imaginal approach to kabbalistic symbolism and the noetic intention of the
      Kabbalah itself in its use of imaginal material. Second, I present a number of
      typical examples of how Jung understands (and sometimes misunderstands)
      kabbalistic material that he cites. Third, I briefly survey the development of
      the Kabbalah as an imaginal noetic system, and present a core self-understanding
      of kabbalists--as engaged in inner 'self-work' which intends to 'sweeten the
      harsh judgments of existence in their very roots'. Finally, I differentiate
      Jung's understanding of the psychical living symbol from the kabbalistic
      understanding of the mystical symbol. In this fourth section of the paper, I
      conclude by presenting a basic Hasidic/kabbalistic teaching on the nature and
      function of verbal contemplative prayer--as an illustration of the difference
      between the two understandings of symbolism. The four sections of the paper are
      framed by a 'Prelude' and a 'Coda'.

PMID- 17537145
TI  - The story of an ambivalent relationship: Sigmund Freud and Eugen Bleuler.
AB  - This paper examines the short-lived flirtation between psychoanalysis and
      academia and psychiatry in Europe and the reasons for, and consequences of, the
      fact that their paths diverged. It is argued that Bleuler's break with the
      psychoanalytic movement is a crucial and, until now, largely underestimated
      turning point. Bleuler's separation from the psychoanalytic movement was probably
      more important for the course it has since taken than those of Adler, Stekel, or
      even Jung. Bleuler's analysis by correspondence by Freud, and its failure, was of
      paramount importance for the future relationship between Freud and Bleuler, and
      for Bleuler's assessment of psychoanalysis.

PMID- 17537151
TI  - Standards and standardization in mastocytosis: consensus statements on
      diagnostics, treatment recommendations and response criteria.
AB  - Although a classification for mastocytosis and diagnostic criteria are available,
      there remains a need to define standards for the application of diagnostic tests,
      clinical evaluations, and treatment responses. To address these demands, leading
      experts discussed current issues and standards in mastocytosis in a Working
      Conference. The present article provides the resulting outcome with consensus
      statements, which focus on the appropriate application of clinical and laboratory
      tests, patient selection for interventional therapy, and the selection of
      appropriate drugs. In addition, treatment response criteria for the various
      clinical conditions, disease-specific symptoms, and specific pathologies are
      provided. Resulting recommendations and algorithms should greatly facilitate the
      management of patients with mastocytosis in clinical practice, selection of
      patients for therapies, and the conduct of clinical trials.

PMID- 17537152
TI  - Atorvastatin therapy improves exercise oxygen uptake kinetics in post-myocardial
      infarction patients.
AB  - BACKGROUND: Statins represent a modern mainstay of the drug treatment of coronary
      artery disease and acute coronary syndromes. Reduced aerobic work performance and
      slowed VO(2) kinetics are established features of the clinical picture of post
      myocardial infarction (MI) patients. We tested the hypothesis that statin therapy
      improves VO(2) exercise performance in normocholesterolaemic post-MI patients.
      MATERIALS AND METHODS: According to a double-blinded, randomized, crossover and
      placebo-controlled study design, in 18 patients with uncomplicated recent (3
      days) MI we investigated the effects of atorvastatin (20 mg day(-1)) on gas
      exchange kinetics by calculating VO(2) effective time constant (tau) during a 50
      watt constant workload exercise, brachial artery flow-mediated dilatation (FMD)
      as an index of endothelial function, left ventricular function (echocardiography)
      and C-reactive protein (CRP, as an index of inflammation). Atorvastatin or
      placebo was given for 3 months each. RESULTS: Atorvastatin therapy significantly
      improved exercise VO(2) tau and FMD, and reduced CRP levels. We did not observe
      changes in cardiac contractile function and relaxation properties during all
      study periods in either group. CONCLUSIONS: In post-MI patients exercise
      performance is a potential additional target of benefits related to statin
      therapy. Endothelial function improvement is very likely implicated in this newly
      described therapeutic property.

PMID- 17537153
TI  - Natriuretic peptides and myocardial oxygen supply-to-demand ratio in patients
      with aortic stenosis.
AB  - BACKGROUND: In severe aortic stenosis (AS), brain natriuretic peptide (BNP) and
      its precursor, the amino-terminal pro-hormone (NT-proBNP) are independent
      predictors of outcome. Deterioration of cardiac function in AS is currently
      assessed by symptomatology and echocardiography to determine the optimal time
      point for surgery. We investigated whether BNP or NT-proBNP may help to estimate
      the individual risk of patients for subendocardial ischaemia in patients with
      moderate and severe AS. DESIGN: In 71 patients with AS and 24 controls, the
      association of plasma natriuretic peptides with invasively measured haemodynamic
      parameters, including the myocardial oxygen supply-to-demand ratio [diastolic
      pressure time index/systolic pressure time index (DPTI/SPTI)] was cross
      sectionally assessed. RESULTS: Levels of natriuretic peptides increased with
      severity of AS. In patients with moderate AS (n = 30), natriuretic peptides
      differentiated between symptomatic and asymptomatic status (P = 0.01). BNP and NT
      proBNP values correlated negatively with DPTI/SPTI (r = -0.58 and -0.51, P <
      0.001, respectively) and left ventricular (LV) ejection fraction (EF) (r = -0.52
      and -0.59, P < 0.001, respectively). DPTI/SPTI correlated with aortic valve area
      (P < 0.0001) but not with EF. Receiver operating characteristic analysis
      determined cut-off values of > 450 pg mL(-1) for BNP and of > 1800 pg mL(-1) for
      NT-proBNP for those AS patients who were at highest risk for subendocardial
      ischaemia (i.e. DPTI/SPTI < 0.22) in combination with impaired LV systolic
      function (i.e. EF < 45%). CONCLUSIONS: Elevated natriuretic peptides show cardiac
      deterioration in AS and may help to identify those patients in need for early
      valve replacement.

PMID- 17537154
TI  - The hepatic lipase gene C-480T polymorphism in the development of early coronary
      atherosclerosis: the Helsinki Sudden Death Study.
AB  - BACKGROUND: The T allele of the hepatic lipase (HL) C-480T polymorphism was
      previously found to be associated with lower post-heparin plasma HL activity,
      atherosclerosis and risk of coronary artery disease. We studied the association
      of HL C-480T polymorphism with the extent of atherosclerosis at vessel-wall level
      in an autopsy series of middle-aged men. MATERIALS AND METHODS: An autopsy cohort
      of 700 Caucasian Finnish men aged 33-70 years (mean 53 years), which comprised
      two autopsy series, collected 10 years apart during 1981-82 and 1991-92, were
      analysed. Areas of coronary wall covered with fatty streaks and fibrotic and
      complicated lesions were measured using computer-assisted planimetry and related
      to HL C-480T genotypes (CC, CT, and TT). RESULTS: There was a significant age-by
      genotype interaction on the mean percentage area of fatty streaks (P = 0.01). The
      HL C-480T polymorphism was a significant explanatory factor for fatty streak area
      in men under 53 years of age with or without age, body mass index, hypertension,
      diabetes, smoking, alcohol consumption, apolipoprotein E genotype, and series
      number as covariates. Men carrying the TT genotype had two times larger areas of
      fatty streaks compared to the CC carriers (8.8% vs. 4.3%, P = 0.009). However,
      this association disappeared in men over 53 years. The areas of more advanced
      atherosclerotic lesions did not vary significantly among the genotype groups.
      CONCLUSIONS: Our results suggest that the HL C-480T polymorphism affects the
      formation of early coronary atherosclerotic lesions in men in their early middle
      age.

PMID- 17537155
TI  - Coronary artery disease investigated using 99mTc-tetrofosmin myocardial SPECT.
AB  - BACKGROUND: Coronary artery disease can be diagnosed from stress and delayed
      images of myocardial single photon emission computed tomography (SPECT) using
      technetium-99 m-tetrofosmin (TcTF). However, the negative predictive value of
      stress SPECT images after a single injection of a low tracer dose remains
      unknown. Thus, the present study investigates whether normal stress SPECT results
      predict event-free survival. MATERIALS AND METHODS: We screened 302 consecutive
      patients who were randomly assigned to two groups for myocardial ischaemia using
      either stress SPECT with a low dose of TcTF (296 MBq, TcTF group, n = 150) or
      stress together with rest SPECT using thallium(201) chloride (TlCl, 111 MBq; TlCl
      group, n = 152) as the tracer. A total of 80 patients with abnormal SPECT
      findings were excluded and the remaining 222 with normal results (age, 66.5 +/-
      0.7 years; TcTF/TlCl, 112/110) were enrolled in the present study and followed up
      for 401 +/- 9 days, with the endpoint being ischaemic cardiac events. RESULTS:
      The incidence of cardiac events did not differ between the two groups (0.9% and
      0.0% in TcTF and TlCl groups, respectively). The cost and duration of TcTF and
      TlCl SPECT examinations were about 425 and 603 Euros and 50 and 280 min,
      respectively. CONCLUSIONS: The negative predictive values of stress SPECT using a
      low dose of TcTF and of combined stress and rest SPECT using TlCl did not differ
      and both were clinically acceptable. Thus, stress SPECT using low dose TcTF is
      useful in screening patients for myocardial ischaemia.

PMID- 17537156
TI  - Angiotensin-converting enzyme gene polymorphism and stroke in type 2 diabetic
      patients in Taiwan.
AB  - BACKGROUND: The effect of traditional risk factors on the association between
      angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism
      and stroke was rarely studied previously. We investigated such effect in
      Taiwanese type 2 diabetic patients. MATERIALS AND METHODS: A total of 872 (422
      men and 450 women) patients aged 63.5 (SD: 11.6) years were recruited. Among
      them, 92 cases (48 men and 44 women) had stroke. Polymerase chain reaction was
      used to classify the genotypes as II, ID and DD. Analyses were performed in
      separate sexes. RESULTS: The adjusted odds ratios for stroke for ID vs. II and DD
      vs. II were 0.837 (0.413-1.697) and 1.778 (0.596-5.300), respectively, for men;
      but were 1.700 (0.824-3.505) and 3.706 (1.375-9.985), respectively, for women. In
      models assuming recessive (DD vs. II + ID), dominant (DD + ID vs. II) and
      additive (II = 0, ID = 1 and DD = 2) transmission, none of the odds ratios was
      significant for men; but were all significant for women: 2.784 (1.137-6.818),
      1.996 (1.006-3.962) and 1.877 (1.155-3.050), respectively. In models using
      patients without risk factors (hypertension, obesity, smoking or dyslipidaemia )
      as a referent group and comparing them to patients with the risk factor and with
      ID/II, and with DD genotypes, all models (except for smoking) favoured an
      increasing trend of risk with patients having the risk factor and DD genotype at
      the highest risk in women. Similar trends for hypertension and dyslipidaemia were
      also observed in men. CONCLUSION: Traditional risk factors play an important role
      in the association between the ACE genotypes and stroke. Patients with DD
      genotype and having traditional risk factors are at the highest risk.

PMID- 17537157
TI  - Associations between VHL genotype and clinical phenotype in familial von Hippel
      Lindau disease.
AB  - BACKGROUND: Von Hippel-Lindau (VHL) disease is an autosomal dominant hereditary
      disorder associated with tumours and cysts in the central nervous system (CNS)
      and other visceral organs. Germline mutations in the VHL gene on chromosome 3p25
      26 are considered the cause of this disease. MATERIALS AND METHODS: We studied
      six patients with VHL disease and their relatives. Loss of heterozygosity (LOH)
      was determined by five flanking microsatellite polymorphic markers in the VHL
      locus. Multiplex ligation-dependent probe amplification (MLPA) and quantitative
      real-time polymerase chain reaction (qPCR) amplification were used to detect the
      genomic deletions. Single-strand conformation polymorphism (SSCP) analysis was
      applied to test for sequence variations. RESULTS: Three germline deletions in the
      VHL gene (142.9, 53.3 and 3.3 kb) were found by MLPA. These deletions were
      defined clearly by qPCR analyses. The142.9 kb germline deletion was significantly
      associated with patients with CNS haemangioblastomas (P < 0.01 by Fisher's exact
      test), and one missense mutation (Gln209Arg) was detected from a patient with a
      pancreatic cyst in the same family. LOH was also detected from a patient with
      bilateral renal cell carcinomas. CONCLUSION: Diverse genetic conditions are
      associated with the clinical manifestations of VHL disease. Genomic deletions
      that can be detected by MLPA or qPCR are major causes for this syndrome. Missense
      mutations and LOH accompanying the disease lead to complex clinical symptoms and
      genotypic determination can facilitate a clinical diagnosis because of their
      strong association.

PMID- 17537158
TI  - Age-related changes in bile acid synthesis and hepatic nuclear receptor
      expression.
AB  - BACKGROUND: Recent data highlighted the role of nuclear receptors in the
      transcriptional regulation of the limiting enzyme of bile acid synthesis,
      cholesterol 7alpha-hydroxylase, in cellular and animal models. This study was
      designed to analyze the effects of age on cholesterol 7alpha-hydroxylase and
      related nuclear receptor expression in human livers. DESIGN: Surgical liver
      biopsies were obtained in 23 patients requiring operation on the gastrointestinal
      tract. mRNA levels of cholesterol 7alpha-hydroxylase and related nuclear
      receptors and co-activators were assayed by quantitative real-time RT-PCR. Serum
      levels of 7alpha-hydroxy-4-cholesten-3-one, a marker of bile acid synthesis, were
      assayed by gas-liquid chromatography:mass spectrometry. RESULTS: Ageing was
      inversely correlated with serum 7alpha-hydroxy-4-cholesten-3-one and with
      cholesterol 7alpha-hydroxylase mRNA levels (r = -0.44 and r = -0.45 on a semi-log
      scale, respectively, P < 0.05). Among different nuclear factors, cholesterol
      7alpha-hydroxylase mRNA best correlated with hepatocyte nuclear factor-4 (r =
      0.55 on a log scale, P < 0.05); hepatocyte nuclear factor-4 levels were also
      inversely correlated with age (r = -0.64 on a semi-log scale, P < 0.05). Age was
      inversely correlated with serum insulin-like growth factor-I levels, which were
      directly correlated with hepatocyte nuclear factor-4 and cholesterol 7alpha
      hydroxylase expression. No suppressive effect of short heterodimer partner
      expression on cholesterol 7alpha-hydroxylase was observed. CONCLUSIONS: Ageing
      associates with reduced bile acid synthesis, possibly related to decreased
      hepatic expression of hepatocyte nuclear factor-4 and consequently of cholesterol
      7alpha-hydroxylase. Age-related modifications of the growth hormone/insulin-like
      growth factor axis might play a role. These findings may help to elucidate the
      pathophysiology of age-related modifications of cholesterol metabolism.

PMID- 17537159
TI  - ADMA correlates with portal pressure in patients with compensated cirrhosis.
AB  - BACKGROUND: Chronic liver diseases are frequently complicated by portal
      hypertension, an important component of which is the increased intrahepatic
      vascular resistance, in part related to endothelial dysfunction. Asymmetric
      dimethylarginine (ADMA), an endogenous inhibitor of NO synthase, is an
      established mediator and marker of endothelial dysfunction. We therefore
      investigated the possible implication of ADMA in chronic liver diseases-induced
      portal hypertension. MATERIALS AND METHODS: We studied 39 consecutive patients
      with compensated hepatitis C virus (HCV) related chronic liver diseases. All
      patients underwent hepatic venous pressure gradient (HVPG) measurement, and
      simultaneous blood sampling from the hepatic vein and the pulmonary artery, for
      ADMA and nitrite/nitrate (NOx) plasma level determinations. RESULTS: A positive
      correlation between HVPG and ADMA concentrations in hepatic veins (ADMA-h) was
      found (r = 0.77, P < 0.0001). Moreover, a negative correlation between HVPG and
      NOx concentrations in the hepatic veins (NO-h) (r = -0.50, P = 0.005), and
      between ADMA-h and NO-h was observed (r = -0.40, P = 0.02). ADMA concentrations
      in pulmonary artery (ADMA-p) (0.55 +/- 0.13 micromol L(-1)) were significantly
      higher than in hepatic veins (0.47 +/- 0.09 micromol L(-1)) (P < 0.0001).
      CONCLUSIONS: These results suggest that ADMA may play a pathophysiological role
      in portal hypertension by contributing to the relative intrahepatic NO deficiency
      typical of endothelial dysfunction.

PMID- 17537160
TI  - TGF-beta1 overexpression in the transversalis fascia of patients with direct
      inguinal hernia.
AB  - BACKGROUND: The aetiology of inguinal hernia includes changes in collagen
      turnover and metalloproteinase (MMP) expression, and direct hernia has been
      linked to increased MMP-2 expression. Since transforming growth factor beta1
      (TGFbeta1) plays a role in tissue remodelling, this growth factor could directly
      affect metalloproteinase secretion and thus the proteolytic activity of these
      enzymes. We hypothesized that TGFbeta1 expression could also be altered in direct
      inguinal hernias. MATERIALS AND METHODS: Tissue specimens were obtained from the
      transversalis fascia (TF) of organ donors (controls; n = 10) and patients with
      inguinal hernia (indirect; n = 20/direct; n = 20), who were also divided into two
      groups according to age (20-40/41-60 years). Tissue sections were
      immunohistochemically labelled using anti-LAP TGFbeta1 (latent form) and anti
      TGFbeta1 (active form) antibodies, and fragments of tissue were subjected to
      Western blot analysis. RESULTS: No significant differences in LAP-TGFbeta1
      expression were detected between specimens from control and hernia patients.
      However, significantly higher levels of active TGFbeta1 were detected in the TF
      of patients with direct hernia (P < 0.05). Age affected the expression of the
      growth factor in its active form, and significant differences emerged between
      direct hernias and controls/indirect hernias only in the younger age groups.
      CONCLUSIONS: Our findings indicate overexpression of the active form of TGFbeta1
      in the TF of young patients with direct hernia. This overexpression reflects an
      attempt to counterbalance the enhanced matrix degradation process observed in
      these patients, identifying a subset of patients requiring the use of a
      prosthetic material for primary hernia repair.

PMID- 17537161
TI  - Predicting the development of early skin test sensitization in offspring of
      parents with asthma.
AB  - BACKGROUND: The direct causal relationship between skin sensitization and asthma
      are controversial until now and remains to be further researched. Our aim is to
      analyse the role of parental asthma in the development of skin sensitization in
      offspring. MATERIALS AND METHODS: This study was performed among nuclear families
      (determined by index of asthma patients), and subjects included parents and
      offspring. Parents were subdivided into four phenotypes on the basis of skin
      sensitization (SPT+ or SPT-) and asthma status (AST+ or AST-) and offspring were
      subdivided into three age groups: 3-8, 9-14 and 15-20 years. The main tests
      included a standard questionnaire and skin prick tests. RESULTS: Offspring's skin
      sensitization differed among parental phenotypes at all ages (P < 0.05). In the
      SPT+/AST-, SPT-/AST+ and SPT+/AST+ groups, offspring were significantly more
      likely to be allergic than the ones in SPT-/AST- group at 3-8 years. Offspring
      with at least one parent with asthma were significantly more likely to have
      positive skin prick test response than those with non-asthmatic parents at age 3
      8 years and 9-14 years, but not at 15-20 years among offspring with allergic
      parents. Results were independent of asthma in the children and of the
      characteristics of atopy in the parents. CONCLUSION: Parent asthma history is an
      independent risk factor for allergic sensitization in their offspring in a
      Chinese population.

PMID- 17537162
TI  - School's out: pathways for young people with intellectual disabilities from out
      of-area residential schools or colleges.
AB  - BACKGROUND: Previous research, and official guidance, has suggested that planning
      for the transition between children's and adults' services is failing young
      people with intellectual disabilities and their families in the UK. Youngsters
      placed away from home in residential schools or colleges are likely to be at even
      greater risk of poor transition planning and outcomes, yet there is little
      understanding of what factors parents consider contribute to a smoother
      transition and what a satisfactory outcome would be. METHOD: The parents of 15
      young people from five areas of the UK were interviewed about what they thought
      contributed to a satisfactory pathway for their son or daughter from an out-of
      area residential school or college on to the next phase of their life. RESULTS:
      Parents identified four main process issues: being well-connected with other
      parents or with key professionals; being proactive; having sufficient
      information; and good forward planning. Most considered a good outcome to be if
      the young person was happy, fulfilled and stimulated. CONCLUSIONS: Parents were
      clear about what they thought helped, and there was little disagreement between
      their views. While some of these factors have been previously identified
      regarding the transition of disabled youngsters, they raise some unique issues
      for families with a youngster educated in an out-of-area residential school or
      college.

PMID- 17537163
TI  - Lifestyle and health behaviours of adults with an intellectual disability.
AB  - BACKGROUND: There is currently no published research in Ireland on the health
      behaviours of adults with an intellectual disability (ID). With an increasing age
      profile and similar patterns of morbidity to the general population, the ID
      population would benefit from baseline data from which to establish risk factors.
      METHODS: A questionnaire survey was carried out with 157 carers of people with an
      ID in the west of Ireland. RESULTS: The results of this survey were compared with
      results of a health survey for the general population in the same region. The
      present survey found that 68% of the ID sample was overweight or obese. Levels of
      smoking (2.6%) and regular alcohol consumption (10.3%) were relatively low in
      comparison with the general population. However, participation in exercise and
      adherence to a healthy diet were poor. The level of resident choice and decision
      making did not have any relationship to health behaviours nor did residential
      setting. Finally, there were no gender differences in health and lifestyle
      profiles. CONCLUSION: The results of this study have important implications for
      health promotion interventions for people with an ID.

PMID- 17537164
TI  - Prevalence of people with intellectual disability in the Netherlands.
AB  - BACKGROUND: Since the 1990s, people with intellectual disability (ID) in the
      Netherlands have been moving from institutions to supported accommodation in the
      community. The Government is in need of recent data on the numbers of these
      people, to ensure adequate care provision and funding. This paper reports on the
      prevalence of people with ID in the Netherlands. The research question was: what
      is the lowest and highest estimation of prevalence of people with ID in the
      Netherlands? METHODS: Two extrapolation methods were used, each consisting of a
      number of stages, using general practice databases and ID care services records.
      RESULTS: The prevalence of people with ID in the Netherlands was 0.7% (111,750
      persons). Other assumptions yielded 0.54-0.64%. Arguments for the two
      extrapolation methods and the lowest and highest estimation of prevalence are
      discussed. CONCLUSIONS: Compared with 1988, there has been a slight decrease in
      the prevalence of people with ID in the Netherlands, even though we included all
      age groups and even people with ID of who were not included in ID care services
      records. By using general practitioner databases it was possible to identify
      these not registered people with ID.

PMID- 17537165
TI  - Mortality in adults with moderate to profound intellectual disability: a
      population-based study.
AB  - BACKGROUND: People with intellectual disability (ID) experience a variety of
      health inequalities compared with the general population including higher
      mortality rates. This is the first UK population-based study to measure the
      extent of excess mortality in people with ID compared with the general
      population. METHOD: Indirectly standardized all-cause and disease mortality
      ratios (SMRs) and exact Poisson confidence intervals were calculated by age and
      sex for all adults, aged 20 years or over, with moderate to profound ID living in
      Leicestershire and Rutland, UK, between 1993 and 2005. The general population of
      Leicestershire and Rutland, which has a population of approximately 700,000
      individuals in this age range, was used for comparison. To explore differences
      within the study population, overall SMRs were also calculated by presence of
      Down syndrome and last place of residence (city or county). RESULTS: Of 2436
      adults identified, 409 (17%) died during 23,000 person-years of follow-up. Both
      all-cause and disease-specific mortality were around three times higher than the
      general population but varied considerably with age. The largest differences were
      observed in people in their twenties, where all-cause mortality was almost nine
      times higher in men (SMR=883; 95% CI=560-1325) and more than 17 times higher in
      women (SMR=1722; 95% CI=964-2840). At a particular disadvantage were people with
      Down syndrome and women with ID living in the city. CONCLUSIONS: The relatively
      high SMRs observed in young people and in women, particularly those living in
      inner city areas and with Down syndrome, deserve further investigation for
      possible explanations, including socio-economic factors.

PMID- 17537166
TI  - Drug administration errors in an institution for individuals with intellectual
      disability: an observational study.
AB  - BACKGROUND: Medication errors can result in harm, unless barriers to prevent them
      are present. Drug administration errors are less likely to be prevented, because
      they occur in the last stage of the drug distribution process. This is especially
      the case in non-alert patients, as patients often form the final barrier to
      prevention of errors. Therefore, a study was set up aimed at identifying the
      frequency of drug administration errors and determinants for these errors in an
      institution for individuals with intellectual disability (ID). METHODS: This
      observational study ('disguised observation') was conducted within an institution
      in the Netherlands caring for 2500 individuals with ID and lasted from October to
      December 2004 with a case control design for identifying determinants for errors.
      The institution consists of both day care units and living units (providing full
      time care), located in different towns. For the study, five units from different
      towns were selected. Within each study unit, the administration of drugs to
      patients was observed for 2 weeks. In total, 953 drug administrations to 46
      patients (25 male, mean age 25.8 years, range 2-73 years) were observed. RESULTS:
      With inclusion of wrong time errors, 242 administrations with at least one error
      were observed [frequency=242/953 (25.4%)] and with exclusion 213 administrations
      with at least one error were observed [frequency=213/953 (22.4%)]. Determinants
      associated with errors were routes of administration 'oral by feeding tube' (OR
      189.66; 95% CI 46.16-779.24) and 'inhalation' (OR 9.98; 95% CI 4.78-20.80), the
      units 'adult full-time care' (OR 2.12; 95% CI 1.05-4.35) and 'children daytime
      care' (OR 10.80; 95% CI 4.43-26.29) and the absence of a distribution robot (OR
      4.0; 95% CI 2.67-5.95). None of the identified errors were reported to the
      voluntary reporting system. CONCLUSION: This study shows that administration
      errors in an institution for individuals with ID are common and that they are not
      formally reported to the voluntary reporting system. Furthermore, it identified
      some determinants that may be the focus for future improvements aimed to reduce
      error frequency.

PMID- 17537167
TI  - Parenting by persons with intellectual disability: an explorative study in the
      Netherlands.
AB  - BACKGROUND: As a sequel to a report by the Health Council of the Netherlands on
      contraception in persons with intellectual disabilities (IDs), a fierce debate
      about parenthood by such persons occurred, in which a lack of knowledge about
      parenting competences became clear. Therefore, the Ministry of Health
      commissioned a study investigating examples of 'successful parenthood' by persons
      with IDs. METHODS: In conformity with the literature and with legal categories,
      we defined 'successful parenthood' as 'good enough parenthood', meaning no
      indications for child abuse and/or neglect, no dealings with child protection
      agencies and no legal custody. We combined a nationwide quantitative
      questionnaire study with a qualitative interview study. Questionnaires were sent
      to all institutions involved in caring for persons with ID, interviews were held
      with 'good enough' parents and their professional caregivers, selected on the
      basis of returned questionnaires. RESULTS: Parenthood occurs in around 1.5% of
      persons with ID in the Netherlands and is mostly restricted to those with mild
      handicaps. In total, 51% of the cases were regarded, by caregivers, as not-good
      enough parenthood, 33% were clearly good enough and 16% were doubtful. Predicting
      factors included the ability and the willingness to follow advice, the quality of
      the social network and the acceptance of parenting in the community. However,
      there is not one decisive predicting factor; particularly, the predictive value
      of the IQ alone is small. CONCLUSIONS: A general policy of discouragement of
      parenthood, as advocated by the Dutch Ministry, is not supported by our results;
      moreover, it would probably be impossible and have negative effects on social
      acceptance of parents with ID. The overall conclusion from the study therefore is
      that some kind of balancing model, in which positive and negative factors are
      weighed, may be useful to predict success and need for support.

PMID- 17537168
TI  - Symbols can improve the reading comprehension of adults with learning
      disabilities.
AB  - BACKGROUND: This study aimed to test the hypothesis that adding symbols to
      written text can improve its comprehensibility for adults with learning
      disabilities. METHODS: Nineteen adults with mild or borderline learning
      disabilities attempted to read four short passages of text, two of which had
      Widgit Rebus symbols added to them. Following each passage, they were asked
      questions to test their comprehension. A counterbalanced design was employed.
      RESULTS: Participants' comprehension scores were significantly higher for the
      symbolized passages than the non-symbolized ones. CONCLUSIONS: Adding symbols to
      written text can make comprehension easier for some adults with mild and
      borderline learning disabilities. Future research, exploring how to do this most
      effectively, would be worthwhile.

PMID- 17537169
TI  - Understanding of facial expressions of emotion by children with intellectual
      disabilities of differing aetiology.
AB  - BACKGROUND: Interpreting emotional expressions is a socio-cognitive skill central
      to interpersonal interaction. Poor emotion recognition has been reported in
      autism but is less well understood in other kinds of intellectual disabilities
      (ID), with procedural differences making comparisons across studies and syndromes
      difficult. This study aimed to compare directly facial emotion recognition skills
      in children with fragile X syndrome (FXS), Down's syndrome (DS) and non-specific
      intellectual disability (NSID), contrasting ability and error profiles with those
      of typically developing (TD) children of equivalent cognitive and linguistic
      status. METHODS: Sixty children participated in the study: 15 FXS, 15 DS, 15 NSID
      and 15 TD children. Standardised measures of cognitive, language and
      socialisation skills were collected for all children, along with measures of
      performance on two photo-matching tasks: an 'identity-matching' task (to control
      for basic face-processing ability) and an 'emotion-matching' task (happiness,
      sadness, anger, surprise, fear or disgust). RESULTS: Identity-matching ability
      did not differ across the four child groups. Only the DS group performed
      significantly more poorly on the emotion-matching task and only in comparison to
      the TD group, with fear recognition an area of particular difficulty. CONCLUSION:
      Findings support previous evidence of emotion recognition abilities commensurate
      with overall developmental level in children with FXS or NSID, but not DS. They
      also suggest, however, that syndrome-specific difficulties may be subtle and
      detectable, at least in smaller-scale studies, only in comparison with TD
      matches, and not always across syndromes. Implications for behavioural phenotype
      theory, educational interventions and future research are discussed.

PMID- 17537170
TI  - Levetiracetam for the treatment of epilepsy among adults with intellectual
      disabilities.

PMID- 17537172
TI  - Determination of metastasis-associated proteins in non-small cell lung cancer by
      comparative proteomic analysis.
AB  - The development of metastasis is the leading cause of death and an enormous
      therapeutic challenge in cases of non-small cell lung cancer. To better
      understand the molecular mechanisms underlying the metastasis process and to
      discover novel potential clinical markers for non-small cell lung cancer,
      comparative proteomic analysis of two non-small cell lung cancer cell lines with
      different metastatic potentials, the non-metastatic CL1-0 and highly metastatic
      CL1-5 cell lines, was carried out using two-dimensional electrophoresis followed
      by matrix-assisted laser desorption ionization-time of flight mass spectrometry
      and tandem mass spectrometry. Thirty-three differentially expressed proteins were
      identified unambiguously, among which 16 proteins were significantly upregulated
      and 17 proteins were downregulated in highly metastatic CL1-5 cells compared with
      non-metastatic CL1-0 cells. Subsequently, 8 of 33 identified proteins were
      selected for further validation at the mRNA level using real-time quantitative
      polymerase chain reaction, and three identified proteins, S100A11, PGP 9.5 and
      HSP27, were confirmed by western blotting. The protein S100A11 displaying
      significant differential expression at both the protein and mRNA levels was
      further analyzed by immunohistochemical staining in 65 primary non-small cell
      lung cancer tissues and 10 matched local positive lymph node specimens to explore
      its relationship with metastasis. The results indicated that the upregulation of
      S100A11 expression in non-small cell lung cancer tissues was significantly
      associated with higher tumor-node-metastasis stage (P = 0.001) and positive lymph
      node status (P = 0.011), implying that S100A11 might be an important regulatory
      molecule in promoting invasion and metastasis of non-small cell lung cancer.

PMID- 17537173
TI  - Awareness of and adherence to cancer screening guidelines among health
      professionals in Japan.
AB  - Since 1998 in Japan, guidelines for cancer screening programs have been developed
      and revised by a research group funded by the Ministry of Health, Labour and
      Welfare. However, little is known about health professionals' awareness of and
      adherence to the cancer screening guidelines. Surveys were conducted by mailing
      questionnaires to two target groups of health professionals: local government
      officers of municipal cancer screening programs of 3327 municipalities in 47
      prefectures (local government officers group; n = 3327) and councilors of an
      academic society dealing with a mass survey of gastroenterological cancer (expert
      group; n = 195). The questionnaire contained questions dealing with: (1)
      awareness of and adherence to the cancer screening guidelines published in 2001,
      and (2) basic knowledge of and attitude towards cancer screening. We compared the
      responses of the two groups. The response rate in both groups was approximately
      65%. Over 70% of the respondents were aware of the cancer screening guidelines.
      However, 20% of the local government officers and 35% of the experts thought that
      non-recommended methods could be used for population-based screening. Fifty-six
      percent of the local government officers and 76% of the experts responded that
      there was no problem with using non-recommended methods for opportunistic
      screening. Almost all health professionals believed that screening was 'almost
      always a good idea'. Although the two groups' backgrounds differed, both did not
      sufficiently understand the evidence-based approach for cancer screening. To
      properly conduct evidence-based cancer screening, it is necessary that health
      professionals have an appropriate understanding of the guidelines.

PMID- 17537174
TI  - Pseudomonas corrugata contains a conserved N-acyl homoserine lactone quorum
      sensing system; its role in tomato pathogenicity and tobacco hypersensitivity
      response.
AB  - Pseudomonas corrugata is a phytopathogenic bacterium, causal agent of tomato pith
      necrosis, yet it is an ubiquitous bacterium that is part of the microbial
      community in the soil and in the rhizosphere of different plant species. Although
      it is a very heterogeneous species, all the strains tested were able to produce
      short chain acyl homoserine lactone (AHL) quorum sensing signal molecules. The
      main AHL produced was N-hexanoyl-L-homoserine lactone (C(6)-AHL). An AHL quorum
      sensing system, designated PcoI/PcoR, was identified and characterized. The role
      of the quorum sensing system in the expression of a variety of traits was
      evaluated. Inactivation of pcoI abolished the production of AHLs. The pcoR
      mutant, but not the pcoI mutant, was impaired in swarming, unable to cause a
      hypersensitivity response on tobacco and resulted in a reduced tomato pith
      necrosis phenotype. The pcoI mutant showed a reduced antimicrobial activity
      against various fungi and bacteria when assayed on King's B medium. These results
      demonstrate that the AHL quorum sensing in Ps. corrugata regulates traits that
      contribute to virulence, antimicrobial activity and fitness. This is the first
      report of genes of Ps. corrugata involved in the disease development and
      biological control activity.

PMID- 17537175
TI  - Delineation of epitopes on the Py235 rhoptry antigen of Plasmodium yoelii YM.
AB  - The 235-kDa antigenic rhoptry protein Py235 of Plasmodium yoelii is encoded by a
      large, highly polymorphic gene family. Monoclonal antibodies to some of these
      antigens have been shown to attenuate the virulence of the lethal YM strain of
      the parasite, converting a potentially fatal YM infection to a fulminating one
      typical of the nonlethal 17X strain, by inducing a switch in target cell
      preference from mature red blood cells to reticulocytes. The reason for this is
      not known but would suggest that antigenic determinants of Py235 may be useful in
      or as subunit vaccines. To identify such determinants, we constructed an epitope
      expression library of one Py235 variant and screened the library with the
      antibodies. Thus, we mapped 5- and 12-amino acid epitopes to the C-terminus of
      the antigen. Both epitopes were more reactive with protective than with
      nonprotective monoclonal antibodies. This may explain the differential protection
      conferred by these antibodies upon their passive transfer into mice.

PMID- 17537176
TI  - A novel method to screen genomic libraries that combines genomic immunization
      with the prime-boost strategy.
AB  - We employed a prime-boost regimen in combination with the expression library
      immunization protocol to improve the protective effectiveness of a genomic
      library used as immunogen. To demonstrate the feasibility of this novel strategy,
      we used as a prime a serogroup B Neisseria meningitidis random genomic library
      constructed in a eukaryotic expression vector. Mice immunized with different
      fractions of this library and boosted with a single dose of meningococcal outer
      membrane vesicles elicited higher bactericidal antibody titers compared with mice
      primed with the empty vector. After the boost, passive administration of sera
      from mice primed with two of these fractions significantly reduced the number of
      viable bacteria in the blood of infant rats challenged with live N. meningitidis.
      The method proposed could be applied to the identification of subimmunogenic
      antigens during vaccine candidate screening by employing expression library
      immunization.

PMID- 17537177
TI  - Impact of selected Lactobacillus and Bifidobacterium species on Listeria
      monocytogenes infection and the mucosal immune response.
AB  - The pathogenesis of Listeria monocytogenes depends on its ability to attach to
      and invade the gastrointestinal epithelium and subsequently withstand the host
      immune response. Despite a thorough understanding of the intracellular phase of
      infection, relatively little is known about how the pathogen behaves in the
      gastrointestinal tract and whether it is affected by the presence of host
      commensal microbiota. Lactobacillus and Bifidobacterium are two important genera
      of the human gut microbiota proposed to possess probiotic effects. Here we
      demonstrate that probiotic bacteria significantly inhibit subsequent listerial
      infection in an in vitro C2Bbe1 epithelial cell model. In the case of
      Lactobacilli, inhibition was due to a combination of acid production and
      secretion of an as yet unidentified protein. In the case of Bifidobacterium,
      inhibition was attributable to an extracellular proteinaceous secreted compound.
      In addition, we observed a significant reduction in interleukin-8 and an increase
      in IL-10 cytokines secreted from epithelial cells following probiotic
      pretreatment and subsequent infection with Listeria. A reduction in the infection
      of epithelial cells and an altered mucosal immune response suggests that
      probiotic bacteria could be of therapeutic benefit against listerial infection.
      This study infers a role for probiotic bacteria as an antagonist of Li.
      monocytogenes infection.

PMID- 17537178
TI  - Evaluation of biofilm production and prevalence of the icaD gene in methicillin
      resistant and methicillin-susceptible Staphylococcus aureus strains isolated from
      patients with nosocomial infections and carriers.
AB  - Staphylococcus aureus is one of the most important etiological agents responsible
      for healthcare-associated infections and is capable of producing many virulence
      factors including biofilm. The aim of the present study was to analyze the
      correlation between the presence of the icaD and icaA genes and the ability to
      produce biofilm in vitro in 302 methicillin-resistant (MRSA) and 268 methicillin
      sensitive S. aureus (MSSA) strains isolated in the Provincial Hospital in Gdansk.
      Presence of the icaD and icaA genes was detected by PCR and the ability to
      produce biofilm in vitro was measured both spectrophotometrically and via Congo
      Red Agar plate culture methods. We found that 91% of MRSA strains harbored the
      icaD gene. Moreover, all icaD-negative strains were icaA-positive. Of MRSA and
      MSSA strains, 47% and 69%, respectively, produced biofilm in vitro. The level of
      consistency between the two applied phenotypic methods was 96%. Additionally, we
      found that strains with the same biofilm status may be present in asymptomatic
      carriers and cause infections.

PMID- 17537179
TI  - Capsule expression regulated by a two-component signal transduction system in
      Streptococcus iniae.
AB  - Streptococcus iniae causes disease in fish and humans and the presence of capsule
      is associated with virulence. Tn917 transposon mutagenesis was performed to
      identify capsule-associated genes and a mutant was isolated, with an insertion in
      a genetic locus encoding a two-component signal transduction system (TCS), which
      we termed sivS/R. sivS and sivR encode a 506-amino-acid (aa) putative histidine
      kinase and a 223-aa putative response regulator, respectively. In order to
      investigate the role of sivS/R, a deletion-insertion mutant was constructed using
      a PCR ligation technique. Real-time PCR showed that transcription of cpsA, the
      first gene in the S. iniae capsule operon, was reduced in the mutant, indicating
      that sivS/R regulates expression of this gene at the transcriptional level. Whole
      human blood killing assays demonstrated that unlike the parent, the mutant was
      susceptible to phagocytosis. Transmission electron microscopy showed
      exopolysaccharide on the surface of the parent strain but not the mutant which
      showed aberrant asymmetric septae that resulted in clumps of abnormal-shaped
      cells. Exponential growth rates of the mutant and parent strain were similar,
      although the mutant exhibited a longer lag phase. We conclude that sivS/R
      regulates capsule expression, thus affecting the ability to evade phagocytosis.

PMID- 17537180
TI  - Candida species fail to produce the immunosuppressive secondary metabolite
      gliotoxin in vitro.
AB  - Yeasts of the genus Candida are a major cause of morbidity and mortality in
      immunocompromised patients. Despite new insights in recent years, the
      pathogenesis of Candida infection is still incompletely understood. Previous
      studies have suggested that gliotoxin, a secondary fungal metabolite with well
      known immunosuppressive effects, is produced by various species of the genus
      Candida, and a possible role of gliotoxin as a virulence factor of C. albicans
      has also been discussed. However, until now, no definitive evidence has been
      provided that members of the genus Candida are able to produce gliotoxin. To
      clarify this question, we tested a total of 100 clinical isolates of C. albicans,
      C. glabrata, C. tropicalis, C. krusei and C. parapsilosis for gliotoxin
      production using a highly sensitive HPLC protocol, and, for selected isolates,
      confirmed our findings by tandem MS. This approach did not detect intracellular
      or extracellular gliotoxin production by any of the isolates examined, although
      various culture conditions were applied. Therefore, in contrast to previous
      studies, our data strongly suggest that at least the Candida species investigated
      in this study are not able to produce the secondary metabolite gliotoxin.

PMID- 17537181
TI  - Production of interleukin-6 in Arxula adeninivorans, Hansenula polymorpha and
      Saccharomyces cerevisiae by applying the wide-range yeast vector (CoMed) system
      to simultaneous comparative assessment.
AB  - A wide-range yeast vector (CoMed) system has been applied to the comparative
      assessment of three different yeast platforms for the production of human
      interleukin-6. A vector equipped with an rRNA gene targeting sequence and an
      Arxula adeninivorans-derived LEU2 gene was used for simultaneous transformation
      of auxotrophic A. adeninivorans, Hansenula polymorpha and Saccharomyces
      cerevisiae strains. IL6 was expressed under control of the strong constitutive A.
      adeninivorans-derived TEF1 promoter, which is functional in all yeast species
      analyzed so far. Secreted IL-6 was found to be correctly processed from an
      MFalpha1-IL6 precursor in A. adeninivorans only, whereas N-terminally truncated
      proteins were observed in H. polymorpha and S. cerevisiae.

PMID- 17537182
TI  - Single QTL mapping and nucleotide-level resolution of a physiologic trait in wine
      Saccharomyces cerevisiae strains.
AB  - Natural Saccharomyces cerevisiae yeast strains exhibit very large genotypic and
      phenotypic diversity. However, the link between phenotype variation and genetic
      determinism is still difficult to identify, especially in wild populations. Using
      genome hybridization on DNA microarrays, it is now possible to identify single
      feature polymorphisms among divergent yeast strains. This tool offers the
      possibility of applying quantitative genetics to wild yeast strains. In this
      instance, we studied the genetic basis for variations in acetic acid production
      using progeny derived from two strains from grape must isolates. The trait was
      quantified during alcoholic fermentation of the two strains and 108 segregants
      derived from their crossing. A genetic map of 2212 markers was generated using
      oligonucleotide microarrays, and a major quantitative trait locus (QTL) was
      mapped with high significance. Further investigations showed that this QTL was
      due to a nonsynonymous single-nucleotide polymorphism that targeted the catalytic
      core of asparaginase type I (ASP1) and abolished its activity. This QTL was only
      effective when asparagine was used as a major nitrogen source. Our results link
      nitrogen assimilation and CO(2) production rate to acetic acid production, as
      well as, on a broader scale, illustrating the specific problem of quantitative
      genetics when working with nonlaboratory microorganisms.

PMID- 17537183
TI  - Quantitative ultrasound and densitometric measurements and laboratory variables
      in patients on long-term acenocoumarol therapy.
AB  - The aim of the study was to establish whether chronic use of acenocomarol affects
      bone metabolism. Eighty-two males [41 treated with acenocumarol (mean therapy
      duration of 6.0+/-6.4 years) and 41 age-matched controls] were studied. Skeletal
      assessment included densitometric measurements at ultradistal forearm and
      calcaneus and ultrasound examination of hand phalanges and laboratory
      measurements included serum total calcium, phosphates, bone alkaline phosphatase
      (bAlp) and C-terminal telo peptide of type I collagen (ICTP). Densitometric and
      ultrasound variables did not differ significantly between patients and controls.
      Mean dose and duration of acenocumarol treatment did not affect skeletal and
      laboratory variables. Bone turnover was depressed, and bAlp and telopeptide were
      significantly lower in patients than in controls (10.0+/-7 vs. 23.0+/14 U/l,
      p<0.05, and 1.6+/-1.3 vs. 3.1+/-1.3 microg/l, respectively). In conclusion,
      despite of the lack of changes in skeletal status, male subjects on long-term
      acenocumarol therapy may be at high risk for fracture due to disturbances in bone
      turnover.

PMID- 17537184
TI  - Times to pain relief and pain freedom with rizatriptan 10 mg and other oral
      triptans.
AB  - BACKGROUND: In the clinical trial setting, oral rizatriptan 10 mg has greater
      efficacy than other oral triptans in freedom from migraine headache pain 2 h
      after dosing. OBJECTIVE: The study objective is to compare the effectiveness of
      rizatriptan 10 mg and other oral triptans for acute migraine attack in a
      naturalistic setting. METHODS: A total of 673 patients took rizatriptan 10 mg or
      their usual-care oral triptans for two migraine attacks in a sequential, cross
      over manner and recorded outcomes using a diary and a stopwatch. Mean and median
      times to pain relief (PR) and pain freedom (PF) for rizatriptan and other oral
      triptans were compared. The effect of rizatriptan on times to PR and PF,
      adjusting for potential confounding factors (treatment sequence, treatment order
      and use of rescue medication), was computed via a Cox proportional hazard model.
      RESULTS: Significantly, more patients taking rizatriptan achieved both PR and PF
      within 2 h after dosing than other oral triptans. Times to PR and PF were shorter
      with rizatriptan than with other oral triptans (median time to PR: 45 vs. 52 min,
      p < 0.0001; median time to PF: 100 vs. 124 min, p < 0.0001). The adjusted
      proportional hazard ratios (rizatriptan vs. other oral triptans) for times to PR
      and PF were 1.32 (95% CI: 1.22-1.44) and 1.27 (95% CI: 1.16-1.39) respectively.
      CONCLUSION: The times to PR and PF in a 'naturalistic' setting were significantly
      shorter for patients treating a migraine attack with rizatriptan 10 mg than with
      other oral triptans.

PMID- 17537185
TI  - Perioperative fluid management: prospective audit.
AB  - BACKGROUND: Postoperative fluid management is a core surgical skill but there are
      few data regarding current fluid management practice and the incidence of
      potential fluid-related complications in general surgical units. We conducted a
      prospective audit of postoperative fluid management and fluid-related
      complications in a consecutive cohort of patients undergoing midline laparotomy.
      METHODS: Over a 6-month period, the peri-operative fluid management of 106
      consecutive patients was prospectively audited. Serum electrolyte data, fluid
      balance data, co-morbidities, operative and anaesthetic variables and quantities
      of fluid and electrolytes prescribed were recorded. The development of fluid
      related and other complications was noted. RESULTS: There were no correlations
      between routinely available fluid balance parameters and the quantities of fluid
      and electrolytes prescribed, suggesting that doctors do not consult fluid balance
      data when prescribing. Fifty-seven patients (54%) developed at least one fluid
      related complication. These patients received significantly greater volumes of
      fluid and sodium each day postoperatively. They had higher rates of other non
      fluid-related complications and death. They had a longer hospital stay. In a
      multivariate model, mean daily fluid load predicted the development of fluid
      related complications. CONCLUSION: Fluid prescription practice in general
      surgical units is sub-optimal, resulting in avoidable iatrogenic complications.
      Involvement of senior staff, education and possibly the introduction of
      prescribing protocols may improve the situation.

PMID- 17537186
TI  - B-type natriuretic peptide as an indicator of right ventricular dysfunction in
      acute pulmonary embolism.
AB  - OBJECTIVE: B-type natriuretic peptide (BNP) is a neurohormone secreted from
      cardiac ventricles in response to ventricular strain. The aim of present study
      was to evaluate the role of BNP in the diagnosis of the right ventricular (RV)
      dysfunction in acute pulmonary embolism (PE). METHODS: BNP levels were measured
      in patients with acute PE as diagnosed by high probability lung scan or positive
      spiral computed tomography. All patients underwent standard echocardiography and
      blood tests during the second hour of the diagnosis. RESULTS: Forty patients
      diagnosed as acute PE (mean age, 60.4 +/- 13.2 years; 62.5% women) were enrolled
      in this study. Patients with RV dysfunction had significantly higher BNP levels
      than patients without RV dysfunction (426 +/- 299.42 pg/ml vs. 39.09 +/- 25.22
      pg/ml, p < 0.001). BNP-discriminated patients with or without RV dysfunction
      (area under the receiver operating characteristic curve, 0.943; 95% CI, 0.863
      1.022). BNP > 90 pg/ml was associated with a risk ratio of 165 (95% CI, 13.7
      1987.2) for the diagnosis of RV dysfunction. There was a significant correlation
      between RV end-diastolic diameter and BNP (r = 0.89, p < 0.001). Sixteen patients
      (40%) were diagnosed as having low-risk PE, 19 patients (47.5%) with submassive
      PE and five patients (12.5%) with massive PE. The mean BNP was 39.09 +/- 25.2,
      378.4 +/- 288.4 and 609.2 +/- 279.2 pg/ml in each group respectively. CONCLUSION:
      Measurement of BNP levels may be a useful approach in diagnosis of RV dysfunction
      in patients with acute PE. The possibility of RV dysfunction in patients with
      plasma BNP levels > 90 pg/ml should be strongly considered.

PMID- 17537187
TI  - Persistent airway inflammation and bronchial hyperresponsiveness in patients with
      totally controlled asthma.
AB  - OBJECTIVE: A proportion of asthmatic patients can achieve total control according
      to the Global Initiative for Asthma/National Institute of Health guidelines. The
      aim of this study was to investigate whether total control of asthma is
      accompanied by the remission of airway inflammation and bronchial
      hyperresponsiveness. METHODS: We assessed the number of eosinophil and the levels
      of eosinophil cationic protein (ECP) and interleukin (IL)-5 in induced sputum and
      bronchial responsiveness to methacholine in 76 patients with totally controlled
      asthma in comparison with 30 current untreated asthmatics and 20 healthy
      subjects. RESULTS: We found significantly higher number of eosinophil and higher
      levels of ECP and IL-5 in the total control group than those in healthy subjects
      (6.9% +/- 3.6% and 1.3% +/- 1.1%, 129.0 +/- 53.8 mug/l and 48.9 +/- 20.4 mug/l,
      22.1 +/- 15.2 mug/l and 10.6 +/- 5.2 mug/l, respectively; p < 0.001), but lower
      than those in current asthma group (16.2% +/- 8.6%, 362.2 +/- 151.6 mug/l, 50.6
      +/-25.8 mug/l, respectively; p < 0.001). Sixty-five (85.5%) patients with totally
      controlled asthma showed positive methacholine challenge test. In the total
      control group, number of eosinophil and the levels of ECP and IL-5 in induced
      sputum of patients with negative methacholine challenge test were significantly
      lower than those in subjects with positive methacholine challenge test (p <
      0.001), whereas sputum number of eosinophil and the levels of ECP and IL-5 in
      patients with negative methacholine challenge test and those of healthy subjects
      were similar (p > 0.05). CONCLUSION: The results of this study suggest that
      airway inflammation and bronchial hyperresponsiveness still persisted during
      total control of asthma.

PMID- 17537188
TI  - Elevated plasma osteopontin level is predictive of cirrhosis in patients with
      hepatitis B infection.
AB  - BACKGROUND: Osteopontin (OPN) was shown to play an important role in the
      pathogenesis of various inflammatory and fibrotic processes and elevated in
      fibrotic liver of mouse model. However, the significance of OPN in hepatitis B
      virus (HBV)-induced liver cirrhosis (LC) remains unclear and is therefore
      evaluated in this study. METHODS: Thirty-nine patients with HBV-induced LC, 30
      patients with HBV infection but without cirrhosis, 11 patients with HBV-related
      hepatocellular carcinoma (HCC) and 14 additional healthy controls were enrolled
      in this study. Plasma levels of OPN were measured with enzyme-linked
      immunosorbent assay and the relationship between OPN and clinical parameters was
      evaluated. RESULTS: When compared to HBV infection group (median 2.16 ng/ml),
      plasma levels of OPN were significantly increased in cirrhosis (4.52 ng/ml, p <
      0.001) and cancer group (13.38 ng/ml, p < 0.001). The OPN level was correlated
      with the severity of liver damage according to Child-Pugh classification (p =
      0.003). It showed at least comparable sensitivity and specificity to predict
      cirrhosis as aspartate aminotransferase to platelet ratio index, a previously
      established non-invasive serum marker of cirrhosis. CONCLUSIONS: These data
      suggest that OPN could be used to evaluate the existence of LC, as OPN has
      previously been reported to be increased in the HCC; this unique feature makes
      OPN a promising candidate for prediction biomarker in the long-time surveillance
      of patients with HBV infection to evaluate the risk of cirrhosis and cancer.

PMID- 17537189
TI  - Perceptual consistency of pain and quality of life between hospice cancer
      patients and family caregivers: a pilot study.
AB  - AIMS: Clinicians usually adjust medical management based on caregivers'
      observation when caring for seriously ill or cognitive-impaired patients. The
      purpose of this study is to research the differences in perceptual congruence of
      patients and caregivers when assessing patients' global pain (GP) and quality of
      life (QOL) in a hospice ward. METHODS: From July 2002 to June 2004, hospice
      inpatients and their family caregivers were invited to participate in this study
      at a medical centre in Southern Taiwan. The survey was cross-sectional,
      incorporating patients' bio-psycho-social factors so as to understand their
      impacts on patients' pain perception and QOL. The bio-psycho-social factors
      included biological pain, physical dependence, financial difficulty, anxiety over
      family, existential meaning of life, uncontrolled outcome of disease and
      insufficient emotional support. RESULTS: Fifty-eight patient/caregiver dyads were
      recruited in the study. The mean of patients' self-reported GP was higher than
      caregivers' rating (5.9 +/- 1.7 vs. 5.1 +/- 1.9, p < 0.05); however, the score of
      patients' QOL was lower in the patients than in the caregivers (6.9 +/- 1.6 vs.
      7.9 +/- 1.4, p < 0.001). The result of regression analyses showed that
      'biological pain', 'religion' and 'gender' were independent variables for
      patients' GP; however, 'biological pain' and 'gender' were factors for patients'
      QOL. No psychosocial factor was revealed as a factor in patient's perception of
      GP or QOL in this survey. CONCLUSION: This study indicates that caregivers have
      the propensity to under-rate patients' pain and overvalue QOL; moreover,
      'religion' and 'gender' influence patients' perception near the end-of-life.
      Therefore, reassessment and proper holistic approach are important in hospice
      care.

PMID- 17537190
TI  - Comparison of risk-adjustment models using administrative or clinical data for
      outcome prediction in patients after myocardial infarction or coronary bypass
      surgery in Korea.
AB  - OBJECTIVE: The objectives of this study were to compare the performance
      indicators of risk-adjustment models based on administrative and clinical data in
      Korea, and to assess whether administrative data alone is useful for comparing
      quality of care. METHODS: Outcome was defined as death within 30 days of
      discharge. For administrative data, the risk factors were; age, sex, and 11 past
      histories and two past major procedures, which were retrospectively chased in
      National Health Insurance database using patient Identification Number. For
      clinical data, the severity score of the three risk-adjustment measures
      [MedisGroups, Disease Staging (DS) and Computerized Severity Index (CSI)] was
      used as the independent predictors of 30-day mortality. Risk-adjustment models
      were developed by logistic regression analysis for 13,885 Acute Myocardial
      Infarction (AMI) and 2115 Coronary Artery Bypass Graft (CABG) patients based on
      administrative data and for 208 AMI patients and 478 CABG patients using clinical
      data. Performances of models were examined using c-statistic and Hosmer-Lemeshow
      statistic. RESULTS: The results obtained showed the superiority of the clinical
      model. For AMI, the c-statistic of the administrative model was 0.696, and those
      of the CSI, DS and MedisGroups models were 0.772, 0.861 and 0.988 respectively.
      For CABG, the c-statistic of the administrative model was 0.568, and those of the
      CSI, DS and MedisGroups models were 0.665, 0.731 and 0.816 respectively.
      CONCLUSION: Our results indicate that risk-adjustment model only using
      administrative data are probably not useful for assessing quality of care in
      Korea.

PMID- 17537191
TI  - Sequential treatment of depression in primary care.
AB  - BACKGROUND: In the past decade, in clinical psychiatry several investigations
      suggested the usefulness of a sequential way of integrating pharmacotherapy and
      psychotherapy in mood disorders. The aim of this paper was to illustrate the
      practical implications of sequential treatment strategy for depression in primary
      care, with particular reference to the increasingly common problem of recurrent
      depression. METHODS: The Authors tried to integrate the evidence which derives
      from meta-analyses and comprehensive general reviews with the insights which
      derive from controlled studies concerned with specific populations. CONCLUSIONS:
      The sequential treatment of mood disorders is an intensive, two-stage approach,
      which derives from the awareness that one course of treatment with a specific
      tool (whether pharmacotherapy or psychotherapy) is unlikely to entail solution to
      the affective disturbances of patients, both in research and in clinical practice
      settings. The aim of the sequential approach is to add therapeutic ingredients as
      long as they are needed. In this sense, it introduces a conceptual shift in
      clinical practice.

PMID- 17537192
TI  - Combined hepatocellular cholangiocarcinoma: prognostic factors investigated by
      computed tomography/magnetic resonance imaging.
AB  - This study was designed to assess the clinical usefulness of imaging for
      predicting the prognosis of patients with combined hepatocellular
      cholangiocarcinoma (cHCC-CC). Between 1999 and 2004, 30 patients with
      histopathologically proven cHCC-CC underwent computed tomography (CT) or magnetic
      resonance imaging (MRI). The imaging data and survival were analysed. Univariate
      log-rank analysis of imaging findings revealed that tumour necrosis, bile duct
      invasion, major vascular branch invasion, multiplicity, bilobar distribution,
      regional lymph node involvement, regional organ invasion, distant metastasis and
      ascites had adverse influences on overall survival. Multivariate Cox proportional
      hazard analysis demonstrated that major vascular branch invasion, regional organ
      invasion, nodal and distant metastases were independent prognostic factors that
      adversely affected overall survival rates. Overall cumulative survival rates at
      1, 3 and 5 years were 53%, 26% and 12%, respectively. Analysing the survival of
      our patients by using clinical stages of the newly updated American Joint
      Committee on Cancer (AJCC) classification for liver neoplasm based on the imaging
      findings, we found significant differences between stages I/II and III (p <
      0.001) and between stages III and IV (p = 0.040). We conclude CT or MRI can be
      used to identify the prognostic factors and to estimate the outcomes of patients
      with cHCC-CC.

PMID- 17537193
TI  - Adult liver abscess: characteristics of patients living in rural north-eastern
      Taiwan.
AB  - AIMS: This study aimed to analyse the characteristics of adult liver abscess (LA)
      patients living in rural townships of Taiwan. PATIENTS AND METHODS: We
      retrospectively screened the electronic admission records of a rural community
      hospital located in north-eastern Taiwan from 1 April, 2002 to 30 April, 2006.
      Relevant data, including subjects' basic characteristics, laboratory findings and
      infectious microorganisms, were extracted. RESULTS: Fifty-six subjects (mean age:
      66.1 +/- 15.9 years; range: 23-94 years) were enrolled; one patient had an
      amoebic LA and 55 had pyogenic LA. Five subjects died in hospital. Overall, 80.5%
      of patients complained of having a fever, 87.5% had single abscess, 71.4% had
      right hepatic lobe involvement and 58.9% underwent invasive drainage. Most
      subjects (66.1%) did not have diabetes mellitus, 94.6% did not have a hepato
      biliary tumour, 73.2% did not have gallstones, 78.6% did not have hepatitis and
      87.5% did not have prior hepato-biliary surgery. Klebsiella pneumoniae was the
      most common infecting microorganism. Previous hepato-biliary surgery and serum
      creatinine >2.0 mg/dl were significantly more common in patients >or=65 years of
      age (p = 0.031). Diabetes mellitus was more common in female subjects (p =
      0.021). Invasive drainage and single abscess were not significantly correlated to
      prognosis. DISCUSSION: Adult LA patients living in rural north-eastern Taiwan
      have different characteristics than patients living in urban areas. Geriatric LA
      patients should be managed cautiously because of the possibility of renal
      insufficiency or previous hepato-biliary surgery. Female LA patients should be
      evaluated for the presence of diabetes mellitus.

PMID- 17537194
TI  - Endoluminal repair of distal aortic arch aneurysms causing aorto-vocal syndrome.
AB  - PURPOSE: We have evaluated the efficacy of endovascular repair of distal aortic
      arch aneurysms (DAAA) causing recurrent laryngeal nerve palsy. MATERIAL AND
      METHODS: Eight patients (five male and three female) with median age of 72 years
      (range: 59-80) presented with left recurrent laryngeal nerve palsy associated
      with DAAA. All patients were considered unfit for open surgery. The median
      aneurysm size was 5.9 cm (range: 5-7.3). Thirteen stents were deployed: eight
      Gore, four Endofit and one Talent. Epidural anaesthesia was used in all patients.
      The left subclavian artery was covered in all and the left common carotid in
      three who had a preliminary right to left carotid-carotid bypass. Routine follow
      up (FU) was with computed tomography (CT) at 3-6 months and yearly thereafter.
      RESULTS: Exclusion of the aneurysm sac was achieved in all patients. Thirty-day
      mortality was 0%, with no paraplegia or stroke. Early complications included:
      rupture of the external iliac artery (one) and common femoral artery thrombectomy
      (one). One patient died of unknown cause at 17 months. The mean FU in the
      remaining seven patients was 21 months (range: 6-51). Aneurysm size decreased in
      five, was unchanged in one and increased in one. Three patients had improvement
      in voice quality postoperatively. One patient had a recurrent type 1 endoleak
      which was restented twice. No late deaths have occurred. CONCLUSION: Though
      technically the procedures involved were more complicated, endovascular repair of
      DAAA causing aorto-vocal syndrome is safe and offers a realistic alternative to
      open surgery. Hoarseness of the voice can improve postoperatively and is
      associated with reduction in aortic sac diameter.

PMID- 17537195
TI  - Improving the quality of life in patients with vestibular disorders: the role of
      medical treatments and physical rehabilitation.
AB  - Vertigo, dizziness and imbalance are the main symptoms of vestibular disorders.
      They can lead to physical consequences, such as reduced postural control and
      falls, to psychologic/psychiatric consequences, such as anxiety-depression
      symptoms, panic and agoraphobia, and to cognitive defects, especially in the
      elderly. Consequently, the general health status and the quality of life (QoL) of
      vestibular patients can be significantly impaired. Several questionnaires have
      been developed in an attempt to quantify the degree of handicap and disability,
      the self-perceived health status and the quality of life in vestibular patients
      with dizziness and imbalance. Additionally, the main goal of the treatments of
      vestibular disorders should be to control symptoms, reduce functional disability
      and to improve patients' QoL. This article reviews the physical and psychological
      consequences of the vestibular disorders, their impact on the patients' QoL, and
      the treatment options, including drug prescriptions and vestibular rehabilitation
      protocols. A profile of the compound betahistine and its efficacy on QoL indices
      in the treatment of Meniere's disease and other forms of peripheral vertigo is
      also presented.

PMID- 17537196
TI  - Relationship between expression and methylation status of p16INK4a and the
      proliferative activity of different areas' tumour cells in human colorectal
      cancer.
AB  - The p16(INK4a) gene is a cell cycle inhibitor and a major tumour suppressor
      protein, but the regulation and effects on tumour cells' invasion process of
      p16(INK4a) is poorly known. A role for p16(INK4a) in basal cell carcinoma is
      suggested by the observation that p16(INK4a) was upregulated at the invasive
      front of the majority of basal cell carcinomas with infiltrative growth patterns,
      accompanied by cessation of proliferation. In this paper, we explore whether
      there is a difference of tumour cells' proliferative activity between the centre
      and the invasion front tissues of human colorectal cancer and its relationship
      with the expression and methylation status of p16(INK4a) gene. We obtained the
      centre and the invasion front tissues of colorectal cancer respectively by the
      technology of laser mircodissection. The expressions of the proliferating cell
      nuclear antigen ki67 and p16(INK4a) were assessed by immunohistochemistry,
      methylation-specific polymerase chain reaction (MS-PCR) and reverse-transcription
      polymerase chain reaction (RT-PCR) in the different areas. There was a
      significant difference in the expressions of ki67 between the centre and the
      invasion front tissues (p < 0.05). The difference did not correlate with age,
      sex, Dukes stage but did correlate with expression of p16(INK4a) gene (chi(2) =
      25.37, p < 0.01). Furthermore, hypermethylation of the promoter was the major
      mechanism of inactivation of p16(INK4a) in the centre areas. Demethylation of the
      p16(INK4a) promoter, the elevated expression of p16(INK4a) protein and mRNA level
      was proved in the invasion front. Our finding suggested that enhanced invasion in
      tumours was accompanied by ceased proliferation in the invasion fronts of human
      colorectal cancer. This interesting phenomenon may be due to not only the
      microenvironment, but also the molecular changes such as p16(INK4a) status.

PMID- 17537198
TI  - Caring for older people with dementia in residential care: nursing students'
      experiences.
AB  - AIM: This paper is a report of selected findings from two projects aimed at
      improving nursing students' experiences of caring for older people in elder care
      settings. BACKGROUND: With a growing number of older people the prevalence of
      dementia is rapidly increasing, such that it is now a primary reason for
      admission to residential care. This has implications for the preparation and
      support of nursing students on clinical placements as people with dementia
      represent a key focus of their nursing activities. METHOD: Two projects were
      conducted in Tasmania between 2001 and 2005, involving 87 second year Bachelor of
      Nursing students who participated in 3-week clinical placements in eight
      residential elder care facilities. During the placements, students and their
      mentors participated in a series of weekly focus group discussions to explore
      their experiences of caring for residents with dementia. Thematic analysis of the
      data was conducted. FINDINGS: Staff in the facilities struggled to support
      students effectively and often failed to recognize that students found residents'
      behaviour disturbing. Despite having some theoretical understanding of dementia,
      students reported being unsure of how to respond to residents and often felt
      scared and intimidated. CONCLUSION: Better preparation and support are needed for
      students on placements involving residents with dementia. Feasible strategies for
      more effective support include increased curriculum content about caring for
      people with dementia, and improved collaboration between university schools of
      nursing and settings for care of older people.

PMID- 17537199
TI  - Measuring individualized nursing care: assessment of reliability and validity of
      three scales.
AB  - AIM: This paper is a report of a study to assess the reliability and convergent
      validity of three measures of nursing care individualization. BACKGROUND:
      Individualized care is a key element of nursing care quality, yet little is known
      about the extent to which it is implemented, its effects, and the factors that
      help or hinder nurses in giving individualized care. Therefore reliable and valid
      instruments are needed to measure individualized nursing care. METHOD: A cross
      sectional correlational survey design was used. The purposive sample consisted of
      861 patients from six hospitals in Finland (response rate 82%). Data were
      collected in 2004. The Individualized Care Scale was administered simultaneously
      with translated versions of the Schmidt's Perceptions of Nursing Care Survey and
      the Oncology Patients' Perceptions of the Quality of Nursing Care Scale. Internal
      consistency reliability and convergent validity were assessed for each scale.
      FINDINGS: Evidence for convergent validity was identified between the
      Individualized Care Scale (part A/B), the Individualization subscale (r = 0.64
      with Part A, r = 0.66 with part B) and the Seeing the Individual Patient subscale
      (r = 0.68 with part A, r = 0.71 with part B). Cronbach alpha coefficient was 0.97
      for the Individualized Care Scale, 0.82 for Seeing the Individual Patient and
      0.87 for the Individualization subscale. CONCLUSION: Data provided preliminary
      evidence for the convergent validity of the individualized care scales, as well
      as acceptable internal consistency reliability for each scale. These scales
      represent useful measures for assessing patients' perceptions of the
      individualization of nursing care received.

PMID- 17537200
TI  - Drug-induced long QT syndrome: a continuing challenge in the field.

PMID- 17537201
TI  - Amiodarone for atrial fibrillation: comfort for the afflicted and affliction for
      the comforted.

PMID- 17537202
TI  - Remodeling of outward K+ currents in pressure-overload heart failure.
AB  - OBJECTIVES: Outward K+ currents are critical determinants of action potential
      repolarization and the site of action of a number of electrophysiologically
      active drugs. Further, expression and processing of the channels underlying these
      currents is altered in heart disease. Here, we investigated the native transmural
      gradient of outward K+ currents in murine left ventricle (LV) and delineated
      disease-related remodeling of these currents in heart failure (HF). METHODS:
      Pressure-overload heart failure was induced in mice by thoracic aortic
      constriction. Outward K+ currents were recorded using the whole-cell patch clamp
      technique in acutely dissociated ventricular myocytes. RESULTS: Unambiguous
      gradients of outward K+ current density and Kv4.2 protein abundance were observed
      across the wall of the LV, with significantly larger current density and protein
      levels in subepicardial (SEP) myocytes, compared with subendocardial (SEN)
      myocytes. Voltage dependences of current activation and inactivation were similar
      in SEP and SEN myocytes. In failing LV, however, outward K+ current density was
      significantly decreased in SEP but not in SEN cells leading to elimination of the
      native transmural gradient. In failing LV, the voltage dependences of K+ current
      activation and inactivation were not altered. However, current inactivation
      (decay) was significantly accelerated and recovery from inactivation was
      significantly slowed. Consistent with this, Western blot analysis revealed a
      decrease in KChIP2 protein abundance in failing LV. CONCLUSIONS: This is the
      first report of HF-related remodeling of outward K+ currents in murine LV.
      Similar to humans, disease-related remodeling occurs differentially across the
      murine ventricular wall, leading to loss of the native gradient of
      repolarization. Together with slowed recovery from inactivation, these
      alterations likely promote abnormal impulse conduction, a major proarrhythmic
      mechanism.

PMID- 17537203
TI  - Structural changes following linear ablation in the left atrium for treatment of
      atrial fibrillation.

PMID- 17537204
TI  - The Pacing to Avoid Cardiac Enlargement (PACE) trial: clinical background,
      rationale, design, and implementation.
AB  - BACKGROUND: Deleterious effect on left ventricular (LV) function was observed
      with conventional right ventricular apical (RVA) pacing. Preliminary data
      suggested that biventricular pacing (BiV) may be superior to RVA pacing in
      patients with LV systolic dysfunction. However, the optimal pacing mode and
      site(s) for patients with normal LV systolic function remain controversial.
      METHODS: The Pacing to Avoid Cardiac Enlargement (PACE) trial is a prospective,
      multicenter, randomized, double blinded, parallel, controlled study aiming to
      determine if BiV pacing is better than conventional RVA pacing in preserving LV
      systolic function and preventing remodeling in patients with LV ejection fraction
      (EF) > or = 45% indicated for pacing. This study targets to recruit 200 patients
      from various centers in Asia, all of whom will receive BiV pacemaker implantation
      before being randomized to either atrial-based RVA or BiV pacing for 1 year.
      Their echocardiographic parameters including LV volumes, left ventricular
      ejection fraction (LVEF), and dyssynchrony index by tissue Doppler imaging,
      exercise capacity, quality of life assessment, neurohormone levels, and clinical
      events will be assessed before and after pacing. The primary endpoints are
      changes in LV end-systolic volume and LVEF 1 year after pacing. It is designed
      with 90% power to detect a 5% difference in the LVEF after 1 year of pacing. The
      enrollment began in 2006. It is expected to conclude at the end of 2008.
      CONCLUSION: The PACE trial will determine whether atrial-based BiV pacing can
      preserve LV systolic function and prevent LV adverse remodeling induced by
      conventional RVA pacing in patients with normal LV systolic function and standard
      pacing indication.

PMID- 17537205
TI  - Prospective randomized comparison of 8-mm gold-tip, externally irrigated-tip and
      8-mm platinum-iridium tip catheters for cavotricuspid isthmus ablation.
AB  - INTRODUCTION: Radiofrequency (RF) ablation of the cavotricuspid isthmus (CTI) can
      be performed using different types of ablation catheter. Gold tip electrodes have
      the theoretical advantage of creating bigger lesions than standard platinum
      iridium electrode. This prospective, randomized study compares the clinical
      efficacy of 8-mm gold tip catheter, externally irrigated and 8-mm platinum
      iridium tip (Pt tip) catheters. METHODS AND RESULTS: Sixty consecutive patients
      (51 men, 60 +/- 10 years) undergoing de novo CTI ablation for documented typical
      atrial flutter were randomized to one of the following ablation catheters: 8-mm
      gold tip catheter, an externally irrigated-tip (Irr. tip) catheter, or an 8-mm Pt
      tip catheter. The procedural endpoint was achievement of bidirectional isthmus
      conduction block with < or = 20 minutes of RF energy application. The latter was
      achieved equally with the 3 catheters (95% for gold tip, 100% for irrigated tip,
      95% for Pt tip) and the durations of RF (10 +/- 6, 10 +/- 4, 13 +/- 8 minutes),
      fluoroscopy (12 +/- 6, 12 +/- 7, 15 +/- 12 minutes) and the procedure (34 +/- 23,
      38 +/- 24, 40 +/- 30 minutes) were similar in all groups. The maximal targeted
      power could not be reached in at least one location in 40% of patients with gold
      tip and in 35% of patients with Pt tip catheters whereas it was always achieved
      with an Irr. tip catheter (P = 0.003, P = 0.008). The reduction in impedance
      during RF delivery was greater with Irr. tip (11 +/- 7 ohms) than with gold (7 +/
      4 ohms, P = 0.02) or Pt tip (5 +/- 3 ohms, P = 0.001) catheters. CONCLUSION:
      This study demonstrates equivalent efficacies of gold, platinum-iridium and
      externally Irr. tip catheters for successful de novo ablation of the CTI.

PMID- 17537206
TI  - Utility of atrial and ventricular cycle length variability in determining the
      mechanism of paroxysmal supraventricular tachycardia.
AB  - INTRODUCTION: No prior studies have systematically investigated the diagnostic
      value of cycle length (CL) variability in differentiating the mechanism of
      paroxysmal supraventricular tachycardia (PSVT). METHODS AND RESULTS: We studied
      173 consecutive patients with PSVT; 86 typical atrioventricular nodal reentrant
      tachycardia (AVNRT), 11 atypical AVNRT, 47 orthodromic reciprocating tachycardia
      (ORT), and 29 with atrial tachycardia (AT). Two consecutive atrial cycles that
      displayed the most CL variability were selected for analysis. One hundred and
      twenty-six patients (73%) had > or = 15 msec variability in tachycardia CL. The
      change in atrial CL predicted the change in subsequent ventricular CL in six of
      eight patients (75%) with atypical AVNRT, 18 of 21 patients (86%) with AT, in
      none of 66 patients with typical AVNRT, and in 32 patients with ORT. The change
      in atrial CL was predicted by the change in preceding ventricular CL in 55 of 66
      patients (83%) with typical AVNRT, no patient with atypical AVNRT, 27 of 31
      patients (87%) with ORT, and one of 21 patients (5%) with AT. The sensitivity,
      specificity, and positive and negative predictive values of a change in atrial CL
      predicting the change in ventricular CL for AT or atypical AVNRT were 83%, 100%,
      100%, and 95%, respectively. The corresponding values for the change in atrial CL
      being predicted by the change in the preceding ventricular CL for typical AVNRT
      or ORT were 85%, 97%, 99%, and 65%, respectively. CONCLUSION: Tachycardia CL
      variability > or = 15 msec is common in PSVT. A change in atrial CL that predicts
      the change in subsequent ventricular CL strongly favors AT or atypical AVNRT. A
      change in atrial CL that is predicted by the change in the preceding ventricular
      CL favors typical AVNRT or ORT.

PMID- 17537207
TI  - Atrial macroreentry tachycardia in patients without obvious structural heart
      disease or previous cardiac surgical or catheter intervention: characterization
      of arrhythmogenic substrates, reentry circuits, and results of catheter ablation.
AB  - INTRODUCTION: Atrial macroreentry tachycardia (AMRT) in patients without obvious
      structural heart disease or previous surgical or catheter intervention has not
      been characterized in detail. METHODS AND RESULTS: Electroanatomical mapping and
      ablation of right or left AMRT were performed in 33 patients. Right atrial
      central conduction obstacle was formed by an electrically silent area (ESA) in 15
      (68%) patients and by a line of double potentials (DPs) in seven (32%) patients.
      Left atrial ESAs were found in all 11 patients with the left AMRT. Reentry
      circuit was reconstructed in 19 (86%) patients with right AMRT and seven (64%)
      patients with left AMRT. Of the ESA-related right AMRT, eight (50%) were double
      loop reentry circuits utilizing a narrow critical isthmus within the ESA and
      eight (50%) were single-loop reentry circuits with a critical isthmus bounded by
      ESA and either ostium of the vena cava. Single-loop DP-related AMRTs had the
      critical isthmus between the DP line and the ostium of the inferior vena cava
      (IVC). Left AMRTs included a variety of single-, double-, or triple-loop reentry
      circuits and their critical isthmuses. During the 37 +/- 15 month follow-up,
      atrial tachyarrhythmia-free clinical outcome was achieved in 21 (95%) patients
      (18 patients, 82%, without antiarrhythmic drugs) with the right AMRT and in nine
      (82%) patients (six patients, 55%, without antiarrhythmic drugs) with the left
      AMRT. CONCLUSION: The majority of right and left AMRTs were related to the
      presence of ESA. Ablation can be successful with a favorable risk of atrial
      tachyarrhythmia recurrence.

PMID- 17537208
TI  - Mapping of epicardial activation in a rabbit model of chronic myocardial
      infarction:.
AB  - INTRODUCTION: This study examines the consequences of a large transmural apical
      infarct on the epicardial electrical activity in isolated rabbit hearts. METHODS
      AND RESULTS: Hearts were isolated 8 weeks after coronary artery ligation.
      Membrane voltage from the epicardial surface of the left ventricle (LV) including
      the infarct was monitored using the voltage sensitive dye RH237. Optical action
      potentials were detected from the epicardial surface of the infarct; the signal
      amplitude was approximately 20% of those in the noninfarcted zone (NZ).
      Epicardial activation mapping of the LV free wall showed that during right atrial
      (RA) pacing, the activation sequence was not significantly different between
      infarcted and sham-operated groups. However, direct stimulation of the epicardium
      in the NZ revealed an area of slow conduction velocity (CV approximately 5 cm/s(
      1), approximately 10% of normal values) at the margin of the infarct zone (IZ).
      Within the IZ, CV was approximately 50% of normal. A prominent endocardial rim of
      myocardium in the infarct was not the source of epicardial optical signals
      because chemical ablation of the endocardium did not affect the epicardial
      activation pattern. CONCLUSION: Therefore, remnant groups of myocytes in the mid
      wall and epicardium of the infarct scar support normal electrical activation
      during RA pacing. Areas of delayed conduction emerge only on epicardial
      stimulation.

PMID- 17537209
TI  - Improved survival associated with prophylactic implantable defibrillators in
      elderly patients with prior myocardial infarction and depressed ventricular
      function: a MADIT-II substudy.
AB  - INTRODUCTION: We aim to evaluate the mortality benefit from defibrillator therapy
      in eligible elderly patients. Effective primary prevention of sudden cardiac
      death with implantable cardioverter defibrillators is well demonstrated in
      patients with coronary disease and depressed ventricular function. METHODS AND
      RESULTS: Among 1,232 patients enrolled with prior infarct and left ventricular
      ejection fraction < or = 0.30, 204 were > or = 75 years old. Of these 204
      patients, 121 underwent defibrillator implant. Relative to the younger patients,
      those > or = 75 years had a higher incidence of atrial fibrillation, elevated
      blood urea nitrogen (BUN), widened QRS, and lower use of beta-blockers and HMG
      CoA reductase inhibitors. Relevant clinical covariates were similar in elderly
      patients randomized to conventional and defibrillator therapy. The hazard ratio
      for the mortality risk in patients > or = 75 years assigned to defibrillator
      implant compared with those in conventional therapy was 0.56 (95 confidence
      interval 0.29-1.08; P = 0.08) after a mean follow-up of 17.2 months.
      Comparatively, the hazard ratio in patients < 75 years assigned to defibrillator
      implant was 0.63 (0.45-0.88; P = 0.01) after 20.8 months. Elderly patients had
      similar reductions in quality of life (QoL) regardless of treatment
      randomization. Scores through Health Utilities Index Mark III (HUI) Questionnaire
      changes from baseline to 1 year were -0.22 for patients with conventional therapy
      versus -0.20 for patients with ICD, and -0.36 versus -0.27 at 2 years,
      respectively (P = NS). CONCLUSION: The implantable defibrillator is associated
      with an equivalent reduction of mortality in elderly and younger patients, with
      no compromise in the QoL in the older age subjects.

PMID- 17537210
TI  - Cellular levels and activity of the flagellar sigma factor FliA of Escherichia
      coli are controlled by FlgM-modulated proteolysis.
AB  - In Escherichia coli the flagellar regulon consists of more than 60 genes
      organized in three hierarchically and temporally regulated transcriptional
      classes. The flagellar sigma factor FliA (sigma(28)) is responsible for class 3
      expression and, in the early phase of flagellar assembly, is inhibited by its
      anti-sigma factor FlgM. The flagellar hook basal body forms a type III secretion
      system capable of secreting both flagellar subunits and FlgM. This results in
      release and therefore activation of FliA and class 3 expression. Here we
      demonstrate that FliA is also subject to proteolysis which mainly depends on Lon
      protease. FlgM not only acts as an anti-sigma factor but also protects FliA from
      being degraded. Based on quantitative measurements over time upon experimental
      induction of the flagellar cascade as well as during the growth cycle of a motile
      strain, we show that FliA proteolysis increases in parallel to class 3
      expression, i.e. correlates with FlgM secretion and the phase of highest activity
      of FliA. Thus, when FlgM is not available due to secretion or mutation, and with
      RNA polymerase interaction being only transient during the transcription
      initiation cycle, the proteases can degrade FliA. Experiments with a lon mutant
      indicate that Lon protease and FliA degradation maintain appropriate FliA : FlgM
      stoichiometry upon induction of the flagellar system and thereby contribute to
      timely shut-off of this system.

PMID- 17537211
TI  - Nuclear localization of dengue virus nonstructural protein 5 through its importin
      alpha/beta-recognized nuclear localization sequences is integral to viral
      infection.
AB  - Dengue virus nonstructural protein 5 (NS5) is a large multifunctional protein
      with a central role in viral replication. We previously identified two nuclear
      localization sequences (NLSs) within the central region of dengue virus type-2
      (DENV-2) NS5 ('aNLS' and 'bNLS') that are recognized by the importin alpha/beta
      and importin beta1 nuclear transporters, respectively. Here, we demonstrate the
      importance of the kinetics of NS5 nuclear localization to virus production for
      the first time and show that the aNLS is responsible. Site-specific mutations in
      the bipartite-type aNLS or bNLS region were introduced into a reporter plasmid
      encoding green fluorescent protein fused to the N-terminus of DENV-2 NS5, as well
      as into DENV-2 genomic length complementary DNA. Mutation of basic residues in
      the highly conserved region of the bNLS did not affect nuclear import of NS5. In
      contrast, mutations in either basic cluster of the aNLS decreased NS5 nuclear
      accumulation and reduced virus production, with the greatest reduction observed
      for mutation of the second cluster (K(387)K(388)K(389)); mutagenesis of both
      clusters abolished NS5 nuclear import and DENV-2 virus production completely. The
      latter appeared to relate to the impaired ability of virus lacking nuclear
      localizing NS5, as compared with wild-type virus expressing nuclear-localizing
      NS5, to reduce interleukin-8 production as part of the antiviral response. The
      results overall indicate that NS5 nuclear localization through the aNLS is
      integral to viral infection, with significant implications for other flaviviruses
      of medical importance, such as yellow fever and West Nile viruses.

PMID- 17537213
TI  - Long-term effects of a short course of neoadjuvant luteinizing hormone-releasing
      hormone analogue and radical radiotherapy on the hormonal profile in patients
      with localized prostate cancer.
AB  - OBJECTIVE: To assess whether a long-term follow-up shows any reduction in the
      level of luteinizing hormone (LH) secretion, which could result in declining
      testosterone levels in men with localized prostate cancer, as most (96%) men have
      testosterone levels within the normal range by 1 year after treatment with a
      short course of LH-releasing hormone analogue (LHRHa) and radiotherapy, and LH
      and follicle stimulating hormone (FSH) remain high at 1 year after treatment,
      maintaining the testosterone levels. PATIENTS AND METHODS: We prospectively
      evaluated 55 patients who previously had a short course of LHRHa (median 97 days,
      range 28-167) and radiotherapy for localized prostate cancer. Eligible patients
      had documented normal testosterone, LH and FSH levels at baseline and at 1-3
      years after radiotherapy. LH, FSH and testosterone were then measured at 5 years
      after treatment. RESULTS: The mean hormone levels before, at 1-3 years and at 5
      years after treatment, respectively, were: testosterone (nmol/L), 15.33, 13.98,
      12.97; LH (U/L), 5.51, 9.95, 6.95; and FSH (U/L), 7.95, 22.40, 17.00. The
      decrease in testosterone level at 5 years vs 1-3 years was not statistically
      significant and was of little clinical relevance (P = 0.057). LH and FSH levels
      were higher at 1-3 years than at baseline and decreased significantly (P < 0.001)
      at 5 years towards the baseline value. The decrease in FSH level was less marked
      than for LH. CONCLUSION: After a short course of LHRHa and radiotherapy, the
      testosterone level was maintained at 5 years. LH levels decreased towards the
      baseline value, suggesting recovery of Leydig cell function. FSH levels remained
      high, suggesting persistent Sertoli cell damage from treatment.

PMID- 17537215
TI  - Venous thromboembolism and cyproterone acetate in men with prostate cancer: a
      study using the General Practice Research Database.
AB  - OBJECTIVE: To evaluate the risk of venous thromboembolism (VTE) associated with
      the use of cyproterone acetate (CPA) amongst men with prostate cancer. PATIENTS
      AND METHODS: Using data from the General Practice Research Database, cases of VTE
      were identified amongst men with prostate cancer. Four controls with no evidence
      of a VTE were selected for each case. The time from diagnosis of prostate cancer
      to first hormonal treatment, and from first hormonal treatment to VTE, was
      compared for different treatments. Adjusted risk estimates for VTE were derived
      from further analysis using a nested case-control study design amongst all men
      with advanced prostate cancer, qualified by evidence of hormonal treatment.
      RESULTS: The time between diagnosis and first treatment was significantly shorter
      for men first treated with CPA than for men first treated with a luteinizing
      hormone releasing hormone (LHRH) analogue (adjusted hazard ratio 1.33, 95%
      confidence interval, CI, 1.06-1.67). When the first treatment was CPA, the
      treatment-free period after diagnosis was significantly shorter for men who later
      had a VTE than for those who did not. The case-control study yielded an adjusted
      risk estimate for VTE amongst CPA users that was significantly higher than
      amongst men who were prescribed an LHRH analogue or who had had an orchidectomy
      (adjusted odds ratio 5.23, 95% CI 3.12-8.79). CONCLUSION: There was a greater
      risk of VTE associated with CPA, which might be due to differences in disease
      severity between users of different products. The clinical significance of this
      finding is unclear.

PMID- 17537216
TI  - Determinants of ejaculatory dysfunction in a community-based longitudinal study.
AB  - OBJECTIVE To analyse the incidence of ejaculatory dysfunction (EJD) and its
      associated bother, and to determine which factors predispose to incident EJD.
      SUBJECTS AND METHODS Men aged 50-78 years, registered in the general practices in
      Krimpen a/d Ijssel, the Netherlands, were recruited. Men were excluded if they
      had a history of prostatectomy, carcinoma of the bladder or prostate and
      neurogenic bladder disease. A baseline study and three follow-up assessments (I
      III), all with questionnaires, i.e. the Benign Prostatic Hyperplasia impact
      index, International Prostate Symptom Score, International Continence Society
      (ICS)male sex questionnaire, and additional measurements, e.g. prostate volume,
      prostate specific antigen, were made at a mean of 2.2-year intervals. We assessed
      the objective variables of EJD as the ability to ejaculate, ejaculatory volume,
      painful ejaculation, and their associated bother (information extracted from the
      ICSmale sex questionnaire). RESULTS At baseline 671 of 1661 (40.4%) men already
      had EJD; the cumulative incidence of EJD was 16.5%, 24.7% and 33.1% after follow
      up I, II and III, respectively. The mean percentage of men who were bothered with
      reduced ejaculatory volume or painful ejaculation was 18.3% and 40.6%,
      respectively. Multivariate analysis showed age, Sickness Impact Profile 'social'
      (questions on social impairment) and erectile dysfunction to be predisposing
      factors of EJD (P < 0.05 and R(2) = 0.048). When EJD was defined as a
      significantly reduced ejaculatory volume or anejaculation only, age and previous
      transurethral resection of the prostate (TURP) were determinants of EJD (P < 0.05
      and R(2) = 0.083). Of the men who had TURP after the follow-up, 51.6% already had
      EJD at baseline. CONCLUSIONS The cumulative incidence of EJD after 6.5 years of
      follow-up was significant (33.1%) and EJD was bothersome, especially in men with
      painful ejaculation. Determinants of EJD were age, social impairment and erectile
      dysfunction. Predisposing factors of significant reduction of ejaculatory volume
      and anejaculation were age and TURP, although 51.6% of men already had EJD before
      TURP. Age appears to be the most significant predisposing factor of EJD.

PMID- 17537217
TI  - Prospective non-randomized evaluation of four mediators of the systemic response
      after extraperitoneal laparoscopic and open retropubic radical prostatectomy.
AB  - OBJECTIVE: To report a prospective, controlled, non-randomized patient study to
      determine the systemic response to extraperitoneal laparoscopic (eLRP) and open
      retropubic radical prostatectomy (RRP). PATIENTS AND METHODS: In all, 403
      patients who had eLRP (163) or open RRP (240) were recruited; patients in both
      groups had similar preoperative staging. In addition to peri-operative variables
      (operative duration, complications, blood loss, transfusion rate,
      hospitalization, catheterization), oncological data (Gleason score, pathological
      stage, positive margins) were also compared. The extent of the systemic response
      to surgery-induced tissue trauma was measured in all patients, by assessing the
      levels of acute-phase markers C-reactive protein (CRP), serum amyloid A (SAA),
      interleukin-6 (IL-6) and IL-10 before, during and after RP. RESULTS: The duration
      of surgery, transfusion rate, hospital stay and duration of catheterization were
      comparable with those in previous studies. There was an increase in IL-6, CRP and
      SAA but no change in IL-10, and no differences between eLRP and RRP over the
      entire period assessed. CONCLUSION: The invasiveness of eLRP could not be
      substantiated objectively based on the variables measured in this study. The
      surgical trauma and associated invasiveness of both methods were equivalent.

PMID- 17537218
TI  - The change in renal function in the supranormal hydronephrotic kidney after
      pyeloplasty.
AB  - OBJECTIVE: To investigate changes in the differential renal function (DRF) before
      and after pyeloplasty in renal units with unilateral pelvi-ureteric junction
      obstruction (PUJO) with supranormal function, and to evaluate the clinical
      significance. PATIENTS AND METHODS: We reviewed the medical and radiographic
      records of 29 children (26 boys and three girls) with unilateral PUJO with a DRF
      (estimated by (99m)Tc-mercaptoacetyltriglycine renal scintigraphy) of >/= 50% in
      the affected renal unit, who had pyeloplasty and were followed for >1 year after
      surgery. Patients were divided into two groups according to the degree of change
      in their DRF to compare the clinical variables, anteroposterior pelvic diameter
      and parenchymal thickness measured by renal ultrasonography. The mean (range)
      follow-up after pyeloplasty was 35 (12-89) months. RESULTS: After pyeloplasty,
      although the mean DRF reduced from 53.8% to 51.4%, in seven (24%) patients the
      DRF decreased significantly (>5%) while most (76%) showed a change of </= 5% of
      the preoperative function, or further improvement. In the seven patients with a
      DRF of >/= 55% before surgery, the DRF afterward was >55% in four and 50-55% in
      one. Between those with and with no significant reduction in DRF, only the
      preoperative renal parenchymal thickness differed significantly (2.78 vs 5.00 mm,
      P = 0.006). CONCLUSION: Supranormal DRF exists and represents the true split
      function of the affected renal unit in patients with adequate renal parenchyma;
      these units maintained the supranormal function after pyeloplasty. Parenchymal
      thickness might be useful to differentiate between the true and false estimates
      and predict surgical outcome before surgery.

PMID- 17537223
TI  - Botulinum toxin a in the overactive bladder: current status and future
      directions.

PMID- 17537219
TI  - Differentiation potential of urothelium from patients with benign bladder
      dysfunction.
AB  - OBJECTIVE: To develop a novel in vitro approach to test the hypothesis that
      failure of urothelial differentiation underlies the aetiopathology of
      interstitial cystitis (IC), where there is evidence of compromised urinary
      barrier function, as benign dysfunctional bladder disease encompass several
      poorly understood clinically defined conditions, including IC, idiopathic
      detrusor overactivity (IDO) and stress urinary incontinence (SUI). MATERIALS AND
      METHODS: Biopsy-derived urothelial cells from dysfunctional bladder biopsies were
      propagated as finite cell lines and examined for their capacity to differentiate
      in vitro, as assessed by the acquisition of a transitional cell morphology, a
      switch from a cytokeratin (CK)13(lo)/CK14(hi) to a CK13(hi)/CK14(lo) phenotype,
      expression of claudin 3, 4 and 5 proteins, and induction of uroplakin gene
      transcription. RESULTS: Two of 12 SUI cell lines showed early senescent changes
      in culture and were not characterized further; one of seven IC, one of five IDO
      and a further three SUI cell lines had some evidence of senescence at passage 3.
      Of the seven IC-derived cell lines, four showed a near normal range of
      differentiation-associated responses, but the remainder showed little or no
      response. Most IDO cell lines (four of five) showed a normal differentiation
      response, but at least three of the 10 SUI cell lines showed some compromise of
      differentiation potential. CONCLUSION: This study supports the existence of a
      subset of patients with IC in whom a failure of urothelial cytodifferentiation
      might contribute to the disease, and provides a novel platform for investigating
      the cell biology of urothelium from SUI and other benign dysfunctional
      conditions.

PMID- 17537224
TI  - Current opinion amongst radiologists and urologists in the uk on percutaneous
      nephrostomy and ureteric stent insertion for acute renal obstruction: results of
      a postal survey.

PMID- 17537225
TI  - Erectile function, sexual drive, and ejaculatory function alter reconstructive
      surgery for anterior urethral stricture disease.

PMID- 17537226
TI  - Influence of nitrate levels in drinking water on urological malignancies: a
      community-based cohort study.

PMID- 17537227
TI  - Fine-touch pressure thresholds in the adult penis.

PMID- 17537228
TI  - Can a slit-like meatus be achieved with the v-incision sutured meatoplasty for
      onlay island flap hypospadias repair?

PMID- 17537229
TI  - Circumcision.

PMID- 17537230
TI  - A curved Lowsley retractor improves manoeuvrability of the prostate during
      ascending radical retropubic prostatectomy.

PMID- 17537231
TI  - Lack of response of alopecia areata to pimecrolimus cream.

PMID- 17537232
TI  - Association of TP53 codon 72 polymorphism and the outcome of adjuvant therapy in
      breast cancer patients.
AB  - INTRODUCTION: Single-nucleotide polymorphisms (SNPs) in codon 72 of the TP53
      (also known as p53) gene (rs1042522) and in the promoter region of the MDM2 gene
      (SNP309; rs2279744) have been suggested to play roles in many cancers. We
      investigated whether these SNPs were associated with patient outcome and the
      effect of adjuvant systemic therapy. METHODS: The genotypes of TP53 codon 72 and
      MDM2 SNP309 were defined among 557 primary Japanese breast cancer patients
      (median follow-up, 61.7 months). The effects of several variables on survival
      were tested by Cox's proportional hazards regression analysis. RESULTS: We showed
      that the Pro/Pro genotype of TP53 codon 72 was associated with poorer disease
      free survival (DFS) than other genotypes by Kaplan-Meier analysis (P = 0.049) and
      multivariate Cox's proportional hazards regression analysis (P = 0.047, risk
      ratio of recurrence = 1.67), whereas MDM2 SNP309 status was not associated with
      DFS. The association of the Pro/Pro TP53 genotype with poorer DFS was especially
      significant in patients who received adjuvant chemotherapy (P = 0.009). In
      contrast, among the patients who had received adjuvant hormonal therapy or no
      adjuvant systemic therapy, TP53 codon 72 genotype was not associated with DFS.
      CONCLUSION: The Pro/Pro genotype of TP53 codon 72 appears to be an independent
      prognostic marker in breast cancer patients.

PMID- 17537233
TI  - High resolution crystal structure of PedB: a structural basis for the
      classification of pediocin-like immunity proteins.
AB  - BACKGROUND: Pediocin-like bacteriocins, ribosomally-synthesized antimicrobial
      peptides, are generally coexpressed with cognate immunity proteins in order to
      protect the bacteriocin-producer from its own bacteriocin. As a step for
      understanding the mode of action of immunity proteins, we determined the crystal
      structure of PedB, a pediocin-like immunity protein conferring immunity to
      pediocin PP-1. RESULTS: The 1.6 A crystal structure of PedB reveals that PedB
      consists of an antiparallel four-helix bundle with a flexible C-terminal end.
      PedB shows structural similarity to an immunity protein against enterocin A (EntA
      im) but some disparity to an immunity protein against carnobacteriocin B2 (ImB2)
      in both the C-terminal conformation and the local structure constructed by
      alpha3, alpha4, and their connecting loop. Structure-inspired mutational studies
      reveal that deletion of the last seven residues of the C-terminus of PedB almost
      abolished its immunity activity. CONCLUSION: The fact that PedB, EntA-im, and
      ImB2 share a four-helix bundle structure strongly suggests the structural
      conservation of this motif in the pediocin-like immunity proteins. The
      significant difference in the core structure and the C-terminal conformation
      provides a structural basis for the classification of pediocin-like immunity
      proteins. Our mutational study using C-terminal-shortened PedBs and the
      investigation of primary sequence of the C-terminal region, propose that several
      polar or charged residues in the extreme C-terminus of PedB which is crucial for
      the immunity are involved in the specific recognition of pediocin PP-1.

PMID- 17537234
TI  - Hypoxic conditions increase hypoxia-inducible transcription factor 2alpha and
      enhance chondrogenesis in stem cells from the infrapatellar fat pad of
      osteoarthritis patients.
AB  - Stem cells derived from the infrapatellar fat pad (IPFP) are a potential source
      of stem cells for the repair of articular cartilage defects. Hypoxia has been
      shown to improve chondrogenesis in adult stem cells. In this study we
      investigated the effects of hypoxia on gene expression changes and chondrogenesis
      in stem cells from the IPFP removed from elderly patients with osteoarthritis at
      total knee replacement. Adherent colony-forming cells were isolated and cultured
      from the IPFP from total knee replacement. The cells at passage 2 were
      characterised for stem cell surface epitopes, and then cultured for 14 days as
      cell aggregates in chondrogenic medium under normoxic (20% oxygen) or hypoxic (5%
      oxygen) conditions. Gene expression analysis, DNA and glycosoaminoglycan assays
      and immunohistochemical staining were determined to assess chondrogenesis. IPFP
      derived adherent colony-forming cells stained strongly for markers of adult
      mesenchymal stem cells, including CD44, CD90 and CD105, and they were negative
      for the haematopoietic cell marker CD34 and for the neural and myogenic cell
      marker CD56. Cell aggregates of IPFP cells showed a chondrogenic response. In
      hypoxic conditions there was increased matrix accumulation of proteoglycan but
      less cell proliferation, which resulted in 3.5-fold more glycosoaminoglycan per
      DNA after 14 days of culture. In hypoxia there was increased expression of
      hypoxia-inducible transcription factor (HIF)2alpha and not HIF1alpha, and the
      expression of key transcription factors SOX5, SOX6 and SOX9, and that of
      aggrecan, versican and collagens II, IX, X and XI, was also increased. These
      results show that cells with stem cell characteristics were isolated from the
      IPFP of elderly patients with osteoarthritis and that their response to
      chondrogenic culture was enhanced by lowered oxygen tension, which upregulated
      HIF2alpha and increased the synthesis and assembly of matrix during
      chondrogenesis. This has important implications for tissue engineering
      applications of cells derived from the IPFP.

PMID- 17537235
TI  - Front-line bevacizumab in combination with oxaliplatin, leucovorin and 5
      fluorouracil (FOLFOX) in patients with metastatic colorectal cancer: a
      multicenter phase II study.
AB  - PURPOSE: To evaluate the efficacy and the toxicity of front line FOLFOX4 combined
      with bevacizumab in patients with metastatsic CRC (mCRC). PATIENTS AND METHODS:
      Chemotherapy-naive patients with mCRC, received bevacizumab (5 mg/kg every 2
      weeks d1), oxaliplatin (85 mg/m2 on d1), leucovorin (200 mg/m2) on days 1 and 2
      and 5-Fluorouracil (400 mg/m2 as i.v. bolus and 600 mg/m2 as 22 h i.v. continuous
      infusion on days 1 and 2) every 2 weeks. RESULTS: Fifty three patients (46 with a
      PS 0-1) were enrolled. Complete and partial response was achieved in eight
      (15.1%) and 28 (52.8%) patients, respectively (ORR: 67.9%; 95% C.I.: 53.8%-92%);
      11 (20.7%) patients had stable disease and six (11.3%) progressive disease. With
      a median follow up period of 13.5 months, time to tumor progression was 11 months
      while the median survival has not yet been reached; the probability of 1-, 2- and
      3- year survival was 79.8%, 63.8% and 58.3%, respectively; Two patients relapsed
      during the follow up period. Eight (15%) patients underwent metastasectomy with
      R0 resections. Grade 3-4 neutropenia occurred in 15.1% of patients and one (1.9%)
      of them presented febrile neutropenia. Non-hematologic toxicity included grade 3
      diarrhea (7.6%) and grade 2 and 3 neurotoxicity in 16.9 and 15.1% of patients,
      respectively. One (1.9%) patient presented pulmonary embolism and one (1.9%)
      cardiac ischaemia. There was one (1.9%) sudden death after the first cycle.
      CONCLUSION: The combination of FOLFOX4/bevacizumab appears to be highly
      effective, well tolerated and merits further evaluation in patients with mCRC.

PMID- 17537236
TI  - Mammographic density does not correlate with Ki-67 expression or cytomorphology
      in benign breast cells obtained by random periareolar fine needle aspiration from
      women at high risk for breast cancer.
AB  - BACKGROUND: Ki-67 expression is a possible risk biomarker and is currently being
      used as a response biomarker in chemoprevention trials. Mammographic breast
      density is a risk biomarker and is also being used as a response biomarker. We
      previously showed that Ki-67 expression is higher in specimens of benign breast
      cells exhibiting cytologic atypia that are obtained by random periareolar fine
      needle aspiration (RPFNA). It is not known whether there is a correlation between
      mammographic density and Ki-67 expression in benign breast ductal cells obtained
      by RPFNA. METHODS: Included in the study were 344 women at high risk for
      developing breast cancer (based on personal or family history), seen at The
      University of Kansas Medical Center high-risk breast clinic, who underwent RPFNA
      with cytomorphology and Ki-67 assessment plus a mammogram. Mammographic breast
      density was assessed using the Cumulus program. Categorical variables were
      analyzed by chi2 test, and continuous variables were analyzed by nonparametric
      test and linear regression. RESULTS: Forty-seven per cent of women were
      premenopausal and 53% were postmenopausal. The median age was 48 years, median 5
      year Gail Risk was 2.2%, and median Ki-67 was 1.9%. The median mammographic
      breast density was 37%. Ki-67 expression increased with cytologic abnormality
      (atypia versus no atypia; P <or= 0.001) and younger age (<or=50 years versus >50
      years; P <or= 0.001). Mammographic density was higher in premenopausal women (P
      <or= 0.001), those with lower body mass index (P < 0.001), and those with lower 5
      year Gail risk (P = 0.001). Mammographic density exhibited no correlation with Ki
      67 expression or cytomorphology. CONCLUSION: Given the lack of correlation of
      mammographic breast density with either cytomorphology or Ki-67 expression in
      RPFNA specimens, mammographic density and Ki-67 expression should be considered
      as potentially complementary response biomarkers in breast cancer chemoprevention
      trials.

PMID- 17537237
TI  - A real-time view of the TAR:Tat:P-TEFb complex at HIV-1 transcription sites.
AB  - HIV-1 transcription is tightly regulated: silent in long-term latency and highly
      active in acutely-infected cells. Transcription is activated by the viral protein
      Tat, which recruits the elongation factor P-TEFb by binding the TAR sequence
      present in nascent HIV-1 RNAs. In this study, we analyzed the dynamic of the
      TAR:Tat:P-TEFb complex in living cells, by performing FRAP experiments at HIV-1
      transcription sites. Our results indicate that a large fraction of Tat present at
      these sites is recruited by Cyclin T1. We found that in the presence of Tat, Cdk9
      remained bound to nascent HIV-1 RNAs for 71s. In contrast, when transcription was
      activated by PMA/ionomycin, in the absence of Tat, Cdk9 turned-over rapidly and
      resided on the HIV-1 promoter for only 11s. Thus, the mechanism of trans
      activation determines the residency time of P-TEFb at the HIV-1 gene, possibly
      explaining why Tat is such a potent transcriptional activator. In addition, we
      observed that Tat occupied HIV-1 transcription sites for 55s, suggesting that the
      TAR:Tat:P-TEFb complex dissociates from the polymerase following transcription
      initiation, and undergoes subsequent cycles of association/dissociation.

PMID- 17537238
TI  - Performance reporting for consumers: issues for the Australian private hospital
      sector.
AB  - A group of consumers of private hospital services and their carers collaborated
      with staff of a Melbourne private hospital and with industry representatives to
      develop a consumer-driven performance report on cardiac services. During the
      development process participating consumers identified situational and structural
      barriers to their right to be informed of costs, to choice and to quality care.
      Their growing appreciation of these barriers led them to a different perspective
      on performance reporting, which resulted in their redirecting the project. The
      consumer participants no longer wanted a performance report that provided
      comparative quantitative data. Instead they designed a report that outlined the
      structures, systems and processes the hospital had in place to address the
      quality and safety of services provided. In addition, consumer participants
      developed a decision support tool for consumers to use in navigating the private
      health care sector. The journey of these consumers in creating a consumer driven
      performance report for a private hospital service may assist those responsible
      for governance of Australia's health system in choosing appropriate strategies
      and mechanisms to enhance private hospital accountability. The situational and
      institutional industry barriers to choice, information and quality identified by
      these consumers need to be addressed before public performance reporting for
      private hospitals is introduced in Australia.

PMID- 17537239
TI  - Using visual feedback distortion to alter coordinated pinching patterns for
      robotic rehabilitation.
AB  - BACKGROUND: It is common for individuals with chronic disabilities to continue
      using the compensatory movement coordination due to entrenched habits, increased
      perception of task difficulty, or personality variables such as low self-efficacy
      or a fear of failure. Following our previous work using feedback distortion in a
      virtual rehabilitation environment to increase strength and range of motion, we
      address the use of visual feedback distortion environment to alter movement
      coordination patterns. METHODS: Fifty-one able-bodied subjects participated in
      the study. During the experiment, each subject learned to move their index finger
      and thumb in a particular target pattern while receiving visual feedback. Visual
      distortion was implemented as a magnification of the error between the thumb
      and/or index finger position and the desired position. The error reduction
      profile and the effect of distortion were analyzed by comparing the mean total
      absolute error and a normalized error that measured performance improvement for
      each subject as a proportion of the baseline error. RESULTS: The results of the
      study showed that (1) different coordination pattern could be trained with visual
      feedback and have the new pattern transferred to trials without visual feedback,
      (2) distorting individual finger at a time allowed different error reduction
      profile from the controls, and (3) overall learning was not sped up by distorting
      individual fingers. CONCLUSION: It is important that robotic rehabilitation
      incorporates multi-limb or finger coordination tasks that are important for
      activities of daily life in the near future. This study marks the first
      investigation on multi-finger coordination tasks under visual feedback
      manipulation.

PMID- 17537240
TI  - Ethnobotanical remarks on Central and Southern Italy.
AB  - BACKGROUND: The present paper is a brief survey on the ethnobotanical works
      published by the Authors since 1981, concerning the research carried out in some
      southern and central Italian regions. Before Roman domination these territories
      were first inhabited by local people, while the southern areas were colonized by
      the Greeks. These different cultural contributions left certain traces, both in
      the toponyms and in the vernacular names of the plants and, more generally, in
      the culture as a whole. METHODS: Field data were collected through open
      interviews, mainly of farmers, shepherds and elderly people, born or living in
      these areas for a long time. Voucher specimens of collected plants are preserved
      in the respective herbaria of the Authors and in the herbarium of "Roma Tre"
      University. Important contributions have been made by several students native to
      the areas under consideration. A comparative analysis with local specific
      ethnobotanical literature was carried out. RESULTS: The paper reports several
      examples concerning human and veterinary popular medicine and in addition some
      anti-parasitic, nutraceutic, dye and miscellaneous uses are also described.
      Moreover vernacular names and toponyms are cited. Eight regions of central and
      southern Italy (particularly Latium, Abruzzo, Marche and Basilicata) were
      investigated and the data obtained are presented in 32 papers. Most of the
      species of ethnobotanical interest have been listed in Latium (368 species),
      Marche (274) and Abruzzo (203). The paper also highlights particularly
      interesting aspects or uses not previously described in the specific
      ethnobotanical literature. CONCLUSION: Phyto-therapy in central and southern
      Italy is nowadays practised by a few elderly people who resort to medicinal
      plants only for mild complaints (on the contrary food uses are still commonly
      practised). Nowadays therapeutic uses, unlike in the past, are less closely or
      not at all linked to ritual aspects. Several plants deserve to be taken into
      consideration not only from the anthropological or cultural point of view, but
      also for further phyto-chemical investigation. Our studies, as well as those of
      other authors, try to provide an original picture of the local ethno
      biodiversity.

PMID- 17537241
TI  - Adjuvant breast cancer chemotherapy during late-trimester pregnancy: not quite a
      standard of care.
AB  - BACKGROUND: Diagnosis of breast cancer during pregnancy was formerly considered
      an indication for abortion. The pendulum has since swung to the other extreme,
      with most reviews now rejecting termination while endorsing immediate
      anthracycline-based therapy for any pregnant patient beyond the first trimester.
      To assess the evidence for this radical change in thinking, a review of relevant
      studies in the fields of breast cancer chemotherapy, pregnancy, and drug safety
      was conducted. DISCUSSION: Accumulating evidence for the short-term safety of
      anthracycline-based chemotherapy during late-trimester pregnancy represents a
      clear advance over the traditional norm of therapeutic abortion. Nonetheless, the
      emerging orthodoxy favoring routine chemotherapy during gestation should continue
      to be questioned on several grounds: (1) the assumed difference in maternal
      survival accruing from chemotherapy administered earlier--i.e., during pregnancy,
      rather than after delivery--has not been quantified; (2) the added survival
      benefit of adjuvant cytotoxic therapy prescribed within the hormone-rich milieu
      of pregnancy remains presumptive, particularly for ER-positive disease; (3) the
      maternal survival benefit associated with modified adjuvant regimens (e.g.,
      weekly schedules, omission of taxanes, etc.) has not been proven equivalent to
      standard (e.g., post-delivery) regimens; and (4) the long-term transplacental and
      transgenerational hazards of late-trimester chemotherapy are unknown. SUMMARY:
      Although an incrementally increased risk of cancer-specific mortality is
      impossible to exclude, mothers who place a high priority on the lifelong well
      being of their progeny may be informed that deferring optimal chemotherapy until
      after delivery is still an option to consider, especially in ER-positive, node
      negative and/or last-trimester disease.

PMID- 17537242
TI  - "I'm pregnant and I have breast cancer".
AB  - Pregnancy is infrequently complicated by the diagnosis of a concurrent breast
      cancer. This presents a particularly complicated clinical problem. The treatment
      of breast cancer in young women involves a number of difficult decisions
      regarding therapy. These decisions become even more complex when the concerns of
      the safety of an unborn child are added to the equation. For breast cancers
      diagnosed late in the third trimester, it is relatively straight forward to delay
      therapy until after delivery. For women diagnosed earlier in pregnancy, there are
      legitimate concerns that delays in therapy may adversely affect outcomes. While
      there are no randomized trials addressing the optimal treatment of women in this
      situation, there are case reports, case series, and cohort experiences that
      provide some insight. There are recommendations available from an international
      working group and from the National Comprehensive Cancer Network that address the
      treatment of women in this situation. There is general consensus that both
      surgery and chemotherapy are relatively safe after the first trimester of
      pregnancy. It is generally agreed that therapeutic radiation, if necessary,
      should be delayed until completion of pregnancy.

PMID- 17537243
TI  - Are benefits and harms in mammography screening given equal attention in
      scientific articles? A cross-sectional study.
AB  - BACKGROUND: The CONSORT statement specifies the need for a balanced presentation
      of both benefits and harms of medical interventions in trial reports. However,
      invitations to screening and newspaper articles often emphasize benefits and
      downplay or omit harms, and it is known that scientific articles can be
      influenced by conflicts of interest. We wanted to determine if a similar
      imbalance occurs in scientific articles on mammography screening and if it is
      related to author affiliation. METHODS: We searched PubMed in April 2005 for
      articles on mammography screening that mentioned a benefit or a harm and that
      were published in 2004 in English. Data extraction was performed by three
      independent investigators, two unblinded and one blinded for article contents,
      and author names and affiliation, as appropriate. The extracted data were
      compared and discrepancies resolved by two investigators in a combined analysis.
      We defined three groups of authors: (1) authors in specialties unrelated to
      mammography screening, (2) authors in screening-affiliated specialties (radiology
      or breast cancer surgery) who were not working with screening, or authors funded
      by cancer charities, and (3) authors (at least one) working directly with
      mammography screening programmes. We used a data extraction sheet with 17 items
      described as important benefits and harms in the 2002 WHO/IARC-report on breast
      cancer screening. RESULTS: We identified 854 articles, and 143 were eligible for
      the study. Most were original research. Benefits were mentioned more often than
      harms (96% vs 62%, P < 0.001). Fifty-five (38%) articles mentioned only benefits,
      whereas seven (5%) mentioned only harms (P < 0.001). Overdiagnosis was mentioned
      in 35 articles (24%), but was more often downplayed or rejected in articles that
      had authors working with screening, (6/15; 40%) compared with authors affiliated
      by specialty or funding (1/6; 17%), or authors unrelated with screening (1/14;
      7%) (P = 0.03). Benefits in terms of reduced breast cancer mortality were
      mentioned in 109 (76%) articles, and was more often provided as a relative risk
      reduction than an absolute risk reduction, where quantified (45 articles (31%)
      versus 6 articles (3%) (P < 0.001)). CONCLUSION: Scientific articles tend to
      emphasize the major benefits of mammography screening over its major harms. This
      imbalance is related to the authors' affiliation.

PMID- 17537244
TI  - Lack of association between celiac disease and dental enamel hypoplasia in a case
      control study from an Italian central region.
AB  - BACKGROUND: A close correlation between celiac disease (CD) and oral lesions has
      been reported. The aim of this case-control study was to assess prevalence of
      enamel hypoplasia, recurrent aphthous stomatitis (RAS), dermatitis herpetiformis
      and atrophic glossitis in an Italian cohort of patients with CD. METHODS: Fifty
      patients with CD and fifty healthy subjects (age range: 3-25 years), matched for
      age, gender and geographical area, were evaluated by a single trained examiner.
      Diagnosis of oral diseases was based on typical medical history and clinical
      features. Histopathological analysis was performed when needed. Adequate
      univariate statistical analysis was performed. RESULTS: Enamel hypoplasia was
      observed in 26% cases vs 16% in controls (p > 0.2; OR = 1.8446; 95% CI = 0.6886:
      4.9414). Frequency of RAS in the CD group was significantly higher (36% vs 12%; p
      = 0.0091; OR = 4.125; 95% CI = 1.4725: 11.552) in CD group than that in controls
      (36% vs 12%). Four cases of atrophic glossitis and 1 of dermatitis herpetiformis
      were found in CD patients vs 1 and none, respectively, among controls.
      CONCLUSION: The prevalence of enamel hypoplasia was not higher in the study
      population than in the control group. RAS was significantly more frequent in
      patients with CD.

PMID- 17537245
TI  - Concurrent acute illness and comorbid conditions poorly predict antibiotic use in
      upper respiratory tract infections: a cross-sectional analysis.
AB  - BACKGROUND: Inappropriate antibiotic use promotes resistance. Antibiotics are
      generally not indicated for upper respiratory infections (URIs). Our objectives
      were to describe patterns of URI treatment and to identify patient and provider
      factors associated with antibiotic use for URIs. METHODS: This study was a cross
      sectional analysis of medical and pharmacy claims data from the Pennsylvania
      Medicaid fee-for-service program database. We identified Pennsylvania Medicaid
      recipients with a URI office visit over a one-year period. Our outcome variable
      was antibiotic use within seven days after the URI visit. Study variables
      included URI type and presence of concurrent acute illnesses and chronic
      conditions. We considered the associations of each study variable with antibiotic
      use in a logistic regression model, stratifying by age group and adjusting for
      confounders. RESULTS: Among 69,936 recipients with URI, 35,786 (51.2%) received
      an antibiotic. In all age groups, acute sinusitis, chronic sinusitis, otitis, URI
      type and season were associated with antibiotic use. Except for the oldest group,
      physician specialty and streptococcal pharyngitis were associated with antibiotic
      use. History of chronic conditions was not associated with antibiotic use in any
      age group. In all age groups, concurrent acute illnesses and history of chronic
      conditions had only had fair to poor ability to distinguish patients who received
      an antibiotic from patients who did not. CONCLUSION: Antibiotic prevalence for
      URIs was high, indicating that potentially inappropriate antibiotic utilization
      is occurring. Our data suggest that demographic and clinical factors are
      associated with antibiotic use, but additional reasons remain unexplained.
      Insight regarding reasons for antibiotic prescribing is needed to develop
      interventions to address the growing problem of antibiotic resistance.

PMID- 17537246
TI  - In vitro binding and survival assays of Leishmania parasites to peripherical
      blood monocytes and monocyte-derived macrophages isolated from dogs naturally and
      experimentally infected with Leishmania (Leishmania) chagasi.
AB  - BACKGROUND: There are a few works considering the characterization of canine
      monocyte-derived macrophages as well as a standardized procedure for isolation,
      culture, and infection of these cells with Leishmania. We have performed several
      modifications in order to improve the canine monocyte-derived macrophage
      cultures. In addition, we have done a comparative study between monocytes and
      monocyte-derived macrophages from dogs naturally and experimentally infected with
      L. chagasi. RESULTS: In the presence of exogenous serum, opsonized Leishmania
      promastigotes binds better to monocytes/macrophages than without serum.
      Otherwise, this binding occurs due to the strict correlation between the
      opsonized biologic particles with the third receptor of the complement (CR3
      CD11b/CD18). In fact, our assays with CD11b confirmed the importance of this
      receptor for canine cells and the L. chagasi experimental system. Moreover,
      monocytes obtained from naturally infected dogs have shown a higher number of
      monocytes bounded to promastigotes. The experimental results regarding survival
      have shown that promastigote forms of opsonized L. chagasi were more infective,
      because we found higher numbers of promastigotes bound to the different cells. As
      a consequence, after forty-eight hours of binding, higher numbers of amastigotes
      appeared inside monocyte-macrophages. CONCLUSION: These studies have given
      support to continue comparative studies involving canine monocytes, monocyte
      derived macrophages and peritoneal macrophages. Since we have standardized the
      canine cell culture, we are looking forward to determining the phenotypic
      properties of these cells before and after L. chagasi infection using flow
      cytometry.

PMID- 17537247
TI  - Family joint activities in a cross-national perspective.
AB  - BACKGROUND: Parents and children joint activities are considered to be an
      important factor on healthy lifestyle development throughout adolescence. This
      study is a part of the Cross-National Survey on Health Behaviour in School-aged
      Children--World Health Organization Collaborative Study (HBSC). It aims to
      describe family time in joint activities and to clarify the role of social and
      structural family profile in a cross-national perspective. METHODS: The research
      was carried out according to the methodology of the HBSC study using the
      anonymous standardized questionnaire. In total, 17,761 students (8,649 boys and
      9,112 girls) aged 13 and 15 years from 6 European countries (Czech Republic,
      Finland, Greenland, Lithuania, Spain, and Ukraine) were surveyed in the 2001-2002
      school-year. The evaluation of joint family activity is based on 8 items: (1)
      watching TV or a video, (2) playing indoor games, (3) eating meals, (4) going for
      a walk, (5) going places, (6) visiting friends or relatives, (7) playing sports,
      (8) sitting and talking about things (chatting). RESULTS: Students from Spain and
      Ukraine reported spending the most time together with their families in almost
      all kinds of joint activities, whereas students from Greenland and Finland
      reported spending the least of this time. Boys were more likely than girls to be
      spending time together with family. Joint family activity goes into decline in
      age from 13 to 15 years. Variability of family time in a cross-national
      perspective was relatively small and related to children age category.
      Considering national, gender and age differences of studied population groups, we
      found that the distribution of joint family activities tends to be dispersed
      significantly by family structure (intact/restructured family) and family wealth.
      CONCLUSION: Our study compares children and parent joint activities in European
      countries and reveals differences and similarities in these patterns between
      countries. The findings underline the role of family structure
      (intact/restructured family) and family wealth in the distribution of time spent
      in joint family activities, which should be considered by health promoters.

PMID- 17537248
TI  - Academic doctors' views of complementary and alternative medicine (CAM) and its
      role within the NHS: an exploratory qualitative study.
AB  - BACKGROUND: There has been a marked increase in the use of complementary and
      alternative medicine (CAM) in the UK population in recent years. Surveys of
      doctors' perspectives on CAM have identified a variety of views and potential
      information needs. While these are useful for describing the proportions of
      doctors who hold particular attitudes towards CAM, they are less helpful for
      understanding why. In addition, while the views of non-academic doctors have
      begun to be studied, the perspective and rationales of academic doctors remains
      under-researched. It seems important to investigate the views of those with a
      research-orientation, given the emphasis on the need for more scientific evidence
      in recent debates on CAM. METHODS: This exploratory study used qualitative
      methods to explore academic doctors' views of CAM and the rationales they
      provided for their views. A purposeful sampling strategy was used to identify
      doctors with a dual clinical and academic role in the Bristol area, with an
      anticipated variety of views on CAM. Semi-structured interviews were conducted
      with nine doctors. The data were analysed thematically, drawing on the Framework
      Approach. RESULTS: The doctors expressed a spectrum of views on CAM, falling into
      three broad groups: the 'enthusiasts', the 'sceptics' and the 'undecided'.
      Scepticism or uncertainty about the value of CAM was prominent, except among
      those practising a form of CAM. A variety of rationales underpinned their
      perspectives on CAM, a key recurring rationale being their perspective on the
      scientific evidence base. The main themes arising included: the role of doctors'
      professional experiences of conventional medicine and CAM in shaping their
      attitudes towards CAM, doctor-patient communication about CAM and patient
      disclosure, whether there is a need for training and education in CAM for
      doctors, a hierarchy of acceptability of CAM and the nature of evidence; and the
      role of CAM within the NHS. CONCLUSION: Despite the caution or scepticism towards
      CAM expressed by doctors in this study, more open doctor-patient communication
      about CAM may enable doctors' potential concerns about CAM to be addressed, or at
      least enhance their knowledge of what treatments or therapies their patients are
      using. Offering CAM to patients may serve to enhance patients' treatment choices
      and even increase doctors' fulfilment in their practice. However, given the
      recurring concerns about lack of scientific evidence expressed by the doctors in
      this study, perceptions of the evidence base may remain a significant barrier to
      greater integration of CAM within the NHS.

PMID- 17537249
TI  - A convenient catalyst system for microwave accelerated cross-coupling of a range
      of aryl boronic acids with aryl chlorides.
AB  - A convenient microwave accelerated cross-coupling procedure between aryl
      chlorides with a range of boronic acids has been developed. An explanation for
      the low reactivity of highly fluorinated boronic acids in Suzuki coupling is
      provided.

PMID- 17537250
TI  - Posttranslational N-glycosylation of the hepatitis B virus large envelope
      protein.
AB  - BACKGROUND: The addition of N-linked glycans to proteins is normally a
      cotranslational process that occurs during translocation of the nascent protein
      to the endoplasmic reticulum. Here, we report on an exception to this rule
      occurring on the hepatitis B virus (HBV) large L envelope protein that is a
      subject to co-plus posttranslational N-glycosylation. RESULTS: By using an
      improved detection system, we identified so far unrecognized, novel isoforms of
      L. Based on mutational analyses, the use of N-glycosylation inhibitors, and pulse
      chase studies, we showed that these isoforms are due to posttranslational N
      glycan addition to the asparagines 4 and 112 within the preS domain of L. While
      an inhibition of N-glycosylation and glycan trimming profoundly blocked virus
      assembly and release, the posttranslational N-glycosylation of L itself was found
      to be dispensable for HBV morphogenesis. CONCLUSION: These data together with
      previous results implicate that the N-glycosylation requirements of virion
      release are due to functional inhibition of cell glycoproteins engaged by HBV.

PMID- 17537251
TI  - Primary care provider preferences for working with a collaborative support team.
AB  - BACKGROUND: Clinical interventions based on collaborative models require
      effective communication between primary care providers (PCPs) and collaborative
      support teams. Despite growing interest in collaborative care, we have identified
      no published studies describing how PCPs prefer to communicate and interact with
      collaborative support teams. This manuscript examines the communication and
      interaction preferences of PCPs participating in an ongoing randomized clinical
      trial of a collaborative intervention for chronic pain and depression. METHODS:
      The trial is being conducted in five primary care clinics of a Veterans Affairs
      Medical Center. Twenty-one PCPs randomized to the study intervention completed a
      survey regarding preferences for interacting with the collaborative support team.
      RESULTS: A majority of PCPs identified email (95%) and telephone calls (68%) as
      preferred modes for communicating with members of the support team. In contrast,
      only 29% identified in-person communications as preferred. Most PCPs preferred
      that the care manager and physician pain specialist assess patients (76%) and
      make initial treatment changes (71%) without first conferring with the PCP. One
      half wanted to be designated cosigners of all support team notes in the
      electronic medical record, one-half wanted to receive brief and focused
      information rather than in-depth information about their patients, and one-half
      wanted their practice nurses automatically included in communications. Panel size
      was strongly associated (p < 0.001) with preference for brief, to-the-point
      discussions about patients. CONCLUSION: The substantial variation in PCP
      communication preferences suggests the need for knowledge of these preferences
      when designing and implementing collaborative interventions. Additional research
      is needed to understand relationships between clinician and practice
      characteristics and interaction preferences.

PMID- 17537252
TI  - An unexpectedly large and loosely packed mitochondrial genome in the charophycean
      green alga Chlorokybus atmophyticus.
AB  - BACKGROUND: The Streptophyta comprises all land plants and six groups of
      charophycean green algae. The scaly biflagellate Mesostigma viride
      (Mesostigmatales) and the sarcinoid Chlorokybus atmophyticus (Chlorokybales)
      represent the earliest diverging lineages of this phylum. In trees based on
      chloroplast genome data, these two charophycean green algae are nested in the
      same clade. To validate this relationship and gain insight into the ancestral
      state of the mitochondrial genome in the Charophyceae, we sequenced the
      mitochondrial DNA (mtDNA) of Chlorokybus and compared this genome sequence with
      those of three other charophycean green algae and the bryophytes Marchantia
      polymorpha and Physcomitrella patens. RESULTS: The Chlorokybus genome differs
      radically from its 42,424-bp Mesostigma counterpart in size, gene order, intron
      content and density of repeated elements. At 201,763-bp, it is the largest mtDNA
      yet reported for a green alga. The 70 conserved genes represent 41.4% of the
      genome sequence and include nad10 and trnL(gag), two genes reported for the first
      time in a streptophyte mtDNA. At the gene order level, the Chlorokybus genome
      shares with its Chara, Chaetosphaeridium and bryophyte homologues eight to ten
      gene clusters including about 20 genes. Notably, some of these clusters exhibit
      gene linkages not previously found outside the Streptophyta, suggesting that they
      originated early during streptophyte evolution. In addition to six group I and 14
      group II introns, short repeated sequences accounting for 7.5% of the genome were
      identified. Mitochondrial trees were unable to resolve the correct position of
      Mesostigma, due to analytical problems arising from accelerated sequence
      evolution in this lineage. CONCLUSION: The Chlorokybus and Mesostigma mtDNAs
      exemplify the marked fluidity of the mitochondrial genome in charophycean green
      algae. The notion that the mitochondrial genome was constrained to remain compact
      during charophycean evolution is no longer tenable. Our data raise the
      possibility that the emergence of land plants was not associated with a
      substantial gain of intergenic sequences by the mitochondrial genome.

PMID- 17537253
TI  - Higher incidence of persistent chronic infection of Chlamydia pneumoniae among
      coronary artery disease patients in India is a cause of concern.
AB  - BACKGROUND: There is growing evidence that Chlamydia pneumoniae may be involved
      in the pathogenesis of atherosclerosis, as several studies have demonstrated the
      presence of the organism in atherosclerotic lesions. C. pneumoniae infections,
      which are especially persistent infections, have been difficult to diagnose
      either by serological methods or isolation of the organism from the tissue.
      Nucleic Acid Amplification tests (NAATs) has emerged as an important method for
      detecting C. pneumoniae. Inspite of high prevalence of C. pneumoniae specific
      antibodies in coronary heart disease patients, direct detection of C. pneumoniae
      in circulating blood of coronary artery disease (CAD) patients by sensitive
      nucleic acid amplification tests nested PCR (nPCR), multiplex PCR (mPCR) has not
      been carried out is required. Further correlation of the presence of C.
      pneumoniae in blood of CAD patients with C. pneumoniae specific IgA and IgG
      antibodies, which may indicative of the status of infection with the progression
      of atherosclerosis. This will help in order to prepare strategies for the
      antibiotic intervention to avoid the progression towards CAD. METHODS: Venous
      blood was obtained from 91 CAD patients and 46 healthy controls. Nucleic acid
      amplification tests viz. nested-, semi-nested- and multiplex PCR were used for
      detection of C. pneumoniae. ELISA carried out prevalence of C. pneumoniae
      specific IgG and IgA antibodies. RESULTS: 29.67% (27/91) patients were positive
      for C. pneumoniae using nested PCR. The sensitivity and specificity of semi
      nested and multiplex PCR were 37.03%, 96.96% and 22.22%, 100% with respect to
      nested PCR. Positive nPCR patients were compared with presence of C. pneumoniae
      specific IgA, IgA+IgG and IgG antibodies. Among 27 (29.67%) nPCR C. pneumoniae
      positive CAD patients, 11(12%) were IgA positive, 13(14.2%) were IgA+IgG positive
      and only1 (1.1%) was IgG positive. A significant presence of C. pneumoniae was
      detected in heavy smokers, non-alcoholics and with family histories of diabetes
      and blood pressure group of CAD patients by nPCR. CONCLUSION: The results
      indicate synergistic association of C. pneumoniae infection and development of
      CAD with other risk factors. We also detected increased positivity for C.
      pneumoniae IgA than IgG in nPCR positive CAD patients. Positive nPCR findings in
      conjunction with persisting high C. pneumoniae specific antibody strongly suggest
      an ongoing infection.

PMID- 17537254
TI  - Isolation of mesenchymal stem cells from equine umbilical cord blood.
AB  - BACKGROUND: There are no published studies on stem cells from equine cord blood
      although commercial storage of equine cord blood for future autologous stem cell
      transplantations is available. Mesenchymal stem cells (MSC) have been isolated
      from fresh umbilical cord blood of humans collected non-invasively at the time of
      birth and from sheep cord blood collected invasively by a surgical intrauterine
      approach. Mesenchymal stem cells isolation percentage from frozen-thawed human
      cord blood is low and the future isolation percentage of MSCs from cryopreserved
      equine cord blood is therefore expectedly low. The hypothesis of this study was
      that equine MSCs could be isolated from fresh whole equine cord blood. RESULTS:
      Cord blood was collected from 7 foals immediately after foaling. The mononuclear
      cell fraction was isolated by Ficoll density centrifugation and cultured in a
      DMEM low glucose based media at 38.5 degrees C in humidified atmosphere
      containing 5% CO2. In 4 out of 7 samples colonies with MSC morphology were
      observed. Cellular morphology varied between monolayers of elongated spindle
      shaped cells to layered cell clusters of cuboidal cells with shorter cytoplasmic
      extensions. Positive Alizarin Red and von Kossa staining as well as significant
      calcium deposition and alkaline phosphatase activity confirmed osteogenesis.
      Histology and positive Safranin O staining of matrix glycosaminoglycans
      illustrated chondrogenesis. Oil Red O staining of lipid droplets confirmed
      adipogenesis. CONCLUSION: We here report, for the first time, the isolation of
      mesenchymal-like stem cells from fresh equine cord blood and their
      differentiation into osteocytes, chondrocytes and adipocytes. This novel
      isolation of equine cord blood MSCs and their preliminary in vitro
      differentiation positions the horse as the ideal pre-clinical animal model for
      proof-of-principle studies of cord blood derived MSCs.

PMID- 17537255
TI  - Correlates of exercise motivation and behavior in a population-based sample of
      endometrial cancer survivors: an application of the Theory of Planned Behavior.
AB  - BACKGROUND: Despite evidence of the benefits of exercise in cancer survivors,
      exercise participation rates tend to decline after treatments. Few studies have
      examined the determinants of exercise in less common cancer sites. In this study,
      we examined medical, demographic, and social cognitive correlates of exercise in
      endometrial cancer survivors using the Theory of Planned Behavior (TPB). METHODS:
      A mailed survey was completed by 354 endometrial cancer survivors (1 to 10 years
      postdiagnosis) residing in Alberta, Canada. The study was cross-sectional.
      Exercise behavior was assessed using the Godin Leisure Time Exercise
      Questionnaire and the TPB constructs were assessed with standard self-report
      scales. Multiple regression analyses were used to determine the independent
      associations of the TPB constructs with intention and behavior. RESULTS: Chi
      square analyses indicated that marital status (p = .003), income level (p =
      .013), and body mass index (BMI) (p = .020) were associated with exercise. The
      TPB explained 34.1% of the variance in exercise behavior with intention (beta =
      .38, p < .001) and self-efficacy (beta = .18, p = .029) being independent
      correlates. For intention, 38.3% of the variance was explained by the TPB with
      self-efficacy (beta = .34, p < .001) and affective attitude (beta = .30, p <
      .001) being the independent correlates. The TPB mediated the associations of
      marital status and BMI with exercise but not income level. Age and BMI moderated
      the associations of the TPB with intention and behavior. CONCLUSION: The TPB may
      be a useful framework for understanding exercise in endometrial cancer survivors.
      Exercise behavior change interventions based on the TPB should be tested in this
      growing population.

PMID- 17537256
TI  - Characterization of the genomic region containing the Shadow of Prion Protein
      (SPRN) gene in sheep.
AB  - BACKGROUND: TSEs are a group of fatal neurodegenerative diseases occurring in man
      and animals. They are caused by prions, alternatively folded forms of the
      endogenous prion protein, encoded by PRNP. Since differences in the sequence of
      PRNP can not explain all variation in TSE susceptibility, there is growing
      interest in other genes that might have an influence on this susceptibility. One
      of these genes is SPRN, a gene coding for a protein showing remarkable
      similarities with the prion protein. Until now, SPRN has not been described in
      sheep, a highly relevant species in prion matters. RESULTS: In order to
      characterize the genomic region containing SPRN in sheep, a BAC mini-contig was
      built, covering approximately 200,000 bp and containing the genes ECHS1, PAOX,
      MTG1, SPRN, LOC619207, CYP2E1 and at least partially SYCE1. FISH mapping of the
      two most exterior BAC clones of the contig positioned this contig on Oari22q24. A
      fragment of 4,544 bp was also sequenced, covering the entire SPRN gene and 1206
      bp of the promoter region. In addition, the transcription profile of SPRN in 21
      tissues was determined by RT-PCR, showing high levels in cerebrum and cerebellum,
      and low levels in testis, lymph node, jejunum, ileum, colon and rectum.
      CONCLUSION: Annotation of a mini-contig including SPRN suggests conserved linkage
      between Oari22q24 and Hsap10q26. The ovine SPRN sequence, described for the first
      time, shows a high level of homology with the bovine, and to a lesser extent with
      the human SPRN sequence. In addition, transcription profiling in sheep reveals
      main expression of SPRN in brain tissue, as in rat, cow, man and mouse.

PMID- 17537257
TI  - Developmental expression of DAX1 in the European sea bass, Dicentrarchus labrax:
      lack of evidence for sexual dimorphism during sex differentiation.
AB  - BACKGROUND: DAX1 (NR0B1), a member of the nuclear receptors super family, has
      been shown to be involved in the genetic sex determination and in gonadal
      differentiation in several vertebrate species. In the aquaculture fish European
      sea bass, Dicentrarchus labrax, and in the generality of fish species, the
      mechanisms of sex determination and differentiation have not been elucidated. The
      present study aimed at characterizing the European DAX1 gene and its
      developmental expression at the mRNA level. METHODS: A full length European sea
      bass DAX1 cDNA (sbDAX1) was isolated by screening a testis cDNA library. The
      structure of the DAX1 gene was determined by PCR and Southern blot. Multisequence
      alignments and phylogenetic analysis were used to compare the translated sbDAX1
      product to that of other vertebrates. sbDAX1 expression was analysed by Northern
      blot and relative RT-PCR in adult tissues. Developmental expression of mRNA
      levels was analysed in groups of larvae grown either at 15 degrees C or 20
      degrees C (masculinising temperature) during the first 60 days, or two groups of
      fish selected for fast (mostly females) and slow growth. RESULTS: The sbDAX1 is
      expressed as a single transcript in testis and ovary encoding a predicted protein
      of 301 amino acids. A polyglutamine stretch of variable length in different DAX1
      proteins is present in the DNA binding domain. The sbDAX1 gene is composed of two
      exons, separated by a single 283 bp intron with conserved splice sites in same
      region of the ligand binding domain as other DAX1 genes. sbDAX1 mRNA is not
      restricted to the brain-pituitary-gonadal axis and is also detected in the gut,
      heart, gills, muscle and kidney. sbDAX1 mRNA was detected as early as 4 days post
      hatching (dph) and expression was not affected by incubation temperature.
      Throughout gonadal sex differentiation (60-300 dph) no dimorphic pattern of
      expression was observed. CONCLUSION: The sbDAX1 gene and putative protein coding
      region is highly conserved and has a wide pattern of tissue expression. Although
      gene expression data suggests sbDAX1 to be important for the development and
      differentiation of the gonads, it is apparently not sex specific.

PMID- 17537258
TI  - "They think we're OK and we know we're not". A qualitative study of asylum
      seekers' access, knowledge and views to health care in the UK.
AB  - BACKGROUND: The provision of healthcare for asylum seekers is a global issue.
      Providing appropriate and culturally sensitive services requires us to understand
      the barriers facing asylum seekers and the facilitators that help them access
      health care. Here, we report on two linked studies exploring these issues, along
      with the health care needs and beliefs of asylum seekers living in the UK.
      METHODS: Two qualitative methods were employed: focus groups facilitated by
      members of the asylum seeking community and interviews, either one-to-one or in a
      group, conducted through an interpreter. Analysis was facilitated using the
      Framework method. RESULTS: Most asylum seekers were registered with a GP,
      facilitated for some by an Asylum Support nurse. Many experienced difficulty
      getting timely appointments with their doctor, especially for self-limiting
      symptoms that they felt could become more serious, especially in children. Most
      were positive about the health care they received, although some commented on the
      lack of continuity. However, there was surprise and disappointment at the length
      of waiting times both for hospital appointments and when attending accident and
      emergency departments. Most had attended a dentist, but usually only when there
      was a clinical need. The provision of interpreters in primary care was generally
      good, although there was a tension between interpreters translating verbatim and
      acting as patient advocates. Access to interpreters in other settings, e.g. in
      patient hospital stays, was problematic. Barriers included the cost of over-the
      counter medication, e.g. children's paracetamol; knowledge of out-of-hours
      medical care; and access to specialists in secondary care. Most respondents came
      from countries with no system of primary medical care, which impacted on their
      expectations of the UK system. CONCLUSION: Most asylum seekers were positive
      about their experiences of health care. However, we have identified issues
      regarding their understanding of how the UK system works, in particular the role
      of general practitioners and referral to hospital specialists. The provision of
      an Asylum Support nurse was clearly a facilitator to accessing primary medical
      care. Initiatives to increase their awareness and understanding of the UK system
      would be beneficial. Interpreting services also need to be developed, in
      particular their role in secondary care and the development of the role of
      interpreter as patient advocate.

PMID- 17537259
TI  - Potency analysis of cellular therapies: the emerging role of molecular assays.
AB  - Potency testing is an important part of the evaluation of cellular therapy
      products. Potency assays are quantitative measures of a product-specific
      biological activity that is linked to a relevant biological property and,
      ideally, a product's in vivo mechanism of action. Both in vivo and in vitro
      assays can be used for potency testing. Since there is often a limited period of
      time between the completion of production and the release from the laboratory for
      administration to the patient, in vitro assays such are flow cytometry, ELISA,
      and cytotoxicity are typically used. Better potency assays are needed to assess
      the complex and multiple functions of cellular therapy products, some of which
      are not well understood. Gene expression profiling using microarray technology
      has been widely and effectively used to assess changes of cells in response to
      stimuli and to classify cancers. Preliminary studies have shown that the
      expression of noncoding microRNA which play an important role in cellular
      development, differentiation, metabolism and signal transduction can distinguish
      different types of stem cells and leukocytes. Both gene and microRNA expression
      profiling have the potential to be important tools for testing the potency of
      cellular therapies. Potency testing, the complexities associated with potency
      testing of cellular therapies, and the potential role of gene and microRNA
      expression microarrays in potency testing of cellular therapies is discussed.

PMID- 17537260
TI  - Mild episodes of tourniquet-induced forearm ischaemia-reperfusion injury results
      in leukocyte activation and changes in inflammatory and coagulation markers.
AB  - BACKGROUND: Monocytes and neutrophils are examples of phagocytic leukocytes, with
      neutrophils being considered as the 'chief' phagocytic leukocyte. Both monocytes
      and neutrophils have been implicated to play a key role in the development of
      ischaemia-reperfusion injury, where they are intrinsically involved in leukocyte
      endothelial cell interactions. In this pilot study we hypothesised that mild
      episodes of tourniquet induced forearm ischaemia-reperfusion injury results in
      leukocyte activation and changes in inflammatory and coagulation markers.
      METHODS: Ten healthy human volunteers were recruited after informed consent. None
      had any history of cardiovascular disease with each subject volunteer
      participating in the study for a 24 hour period. Six venous blood samples were
      collected from each subject volunteer at baseline, 10 minutes ischaemia, 5, 15,
      30, 60 minutes and 24 hours reperfusion, by means of a cannula from the ante
      cubital fossa. Monocyte and neutrophil leukocyte sub-populations were isolated by
      density gradient centrifugation techniques. Leukocyte trapping was investigated
      by measuring the concentration of leukocytes in venous blood leaving the arm. The
      cell surface expression of CD62L (L-selectin), CD11b and the intracellular
      production of hydrogen peroxide (H2O2) were measured via flow cytometry. C
      reactive protein (CRP) was measured using a clinical chemistry analyser. Plasma
      concentrations of D-dimer and von Willebrand factor (vWF) were measured using
      enzyme-linked fluorescent assays (ELFA). RESULTS: During ischaemia-reperfusion
      injury, there was a decrease in CD62L and an increase in CD11b cell surface
      expression for both monocytes and neutrophils, with changes in the measured
      parameters reaching statistical significance (p =< 0.05). A significant decrease
      in peripheral blood leukocyte concentration was observed during this process,
      which was measured to assess the degree of leukocyte trapping in the micro
      circulation (p =< 0.001). There was an increase in the intracellular production
      of H2O2 production by leukocyte sub-populations, which was measured as a marker
      of leukocyte activation. Intracellular production of H2O2 in monocytes during
      ischaemia-reperfusion injury reached statistical significance (p = 0.014),
      although similar trends were observed with neutrophils these did not reach
      statistical significance. CRP was measured to assess the inflammatory response
      following mild episodes of ischaemia-reperfusion injury and resulted in a
      significant increase in the CRP concentration (p =< 0.001). There were also
      increased plasma concentrations of D-dimer and a trend towards elevated vWF
      levels, which were measured as markers of coagulation activation and endothelial
      damage respectively. Although significant changes in D-dimer concentrations were
      observed during ischaemia-reperfusion injury (p = 0.007), measurement of the vWF
      did not reach statistical significance. CONCLUSION: Tourniquet induced forearm
      ischaemia-reperfusion injury results in increased adhesiveness, trapping and
      activation of leukocytes. We report that, even following a mild ischaemic insult,
      this leukocyte response is immediately followed by evidence of increased
      inflammatory response, coagulation activity and endothelial damage. These results
      may have important implications and this pilot study may lead to a series of
      trials that shed light on the mechanisms of ischaemia-reperfusion injury,
      including potential points of therapeutic intervention for pathophysiological
      conditions.

PMID- 17537261
TI  - Translational control of recombinant human acetylcholinesterase accumulation in
      plants.
AB  - BACKGROUND: Codon usage differences are known to regulate the levels of gene
      expression in a species-specific manner, with the primary factors often cited to
      be mRNA processing and accumulation. We have challenged this conclusion by
      expressing the human acetylcholinesterase coding sequence in transgenic plants in
      its native GC-rich sequence and compared to a matched sequence with
      (dicotyledonous) plant-optimized codon usage and a lower GC content. RESULTS: We
      demonstrate a 5 to 10 fold increase in accumulation levels of the "synaptic"
      splice variant of human acetylcholinesterase in Nicotiana benthamiana plants
      expressing the optimized gene as compared to the native human sequence. Both
      transient expression assays and stable transformants demonstrated conspicuously
      increased accumulation levels. Importantly, we find that the increase is not a
      result of increased levels of acetylcholinesterase mRNA, but rather its
      facilitated translation, possibly due to the reduced energy required to unfold
      the sequence-optimized mRNA. CONCLUSION: Our findings demonstrate that codon
      usage differences may regulate gene expression at different levels and anticipate
      translational control of acetylcholinesterase gene expression in its native
      mammalian host as well.

PMID- 17537262
TI  - Mechanisms of action of inhaled fibers, particles and nanoparticles in lung and
      cardiovascular diseases.
AB  - BACKGROUND: A symposium on the mechanisms of action of inhaled airborne
      particulate matter (PM), pathogenic particles and fibers such as silica and
      asbestos, and nanomaterials, defined as synthetic particles or fibers less than
      100 nm in diameter, was held on October 27 and 28, 2005, at the Environmental
      Protection Agency (EPA) Conference Center in Research Triangle Park, North
      Carolina. The meeting was the eighth in a series of transatlantic conferences
      first held in Penarth, Wales, at the Medical Research Council Pneumoconiosis Unit
      (1979), that have fostered long-standing collaborations between researchers in
      the fields of mineralogy, cell and molecular biology, pathology, toxicology, and
      environmental/occupational health. RESULTS: The goal of this meeting, which was
      largely supported by a conference grant from the NHLBI, was to assemble a group
      of clinical and basic research scientists who presented and discussed new data on
      the mechanistic effects of inhaled particulates on the onset and development of
      morbidity and mortality in the lung and cardiovascular system. Another outcome of
      the meeting was the elucidation of a number of host susceptibility factors
      implicated in adverse health effects associated with inhaled pathogenic
      particulates. CONCLUSION: New models and data presented supported the paradigm
      that both genetic and environmental (and occupational) factors affect disease
      outcomes from inhaled particulates as well as cardiopulmonary responses. These
      future studies are encouraged to allow the design of appropriate strategies for
      prevention and treatment of particulate-associated morbidity and mortality,
      especially in susceptible populations.

PMID- 17537263
TI  - Sensitivity and specificity of monoclonal and polyclonal immunohistochemical
      staining for West Nile virus in various organs from American crows (Corvus
      brachyrhynchos).
AB  - BACKGROUND: Based on results of earlier studies, brain, heart and kidney are most
      commonly used for West Nile virus (WNV) detection in avian species. Both
      monoclonal and polyclonal antibodies have been used for the immunohistochemical
      diagnosis of WNV in these species. Thus far, no studies have been performed to
      compare the sensitivity and specificity of monoclonal and polyclonal antibodies
      in detecting WNV in American crows (Corvus brachyrhynchos). Our objectives were
      to determine 1) the comparative sensitivities of monoclonal and polyclonal
      antibodies for immunohistochemical (IHC) diagnosis of WNV infection in free
      ranging American crows, 2) which organ(s) is/are most suitable for IHC-based
      diagnosis of WNV, and 3) how real-time RT-PCR on RNA extracted from formalin
      fixed paraffin-embedded tissues compared to IHC for the diagnosis of WNV
      infection. METHODS: Various combinations, depending on tissue availability, of
      sections of heart, kidney, brain, liver, lung, spleen, and small intestine from
      85 free-ranging American crows were stained using a rabbit-polyclonal anti-WNV
      antibody as well as a monoclonal antibody directed against an epitope on Domain
      III of the E protein of WNV. The staining intensity and the extent of staining
      were determined for each organ using both antibodies. Real-time RT-PCR on
      formalin-fixed paraffin-embedded tissues from all 85 crows was performed.
      RESULTS: Forty-three crows were IHC-positive in at least one of the examined
      organs with the polyclonal antibody, and of these, only 31 were positive when IHC
      was performed with the monoclonal antibody. Real-time RT-PCR amplified WNV
      specific sequences from tissue extracts of the same 43 crows that were IHC
      positive using the polyclonal antibody. All other 42 crows tested negative for
      WNV with real-time PCR and IHC staining. Both antibodies had a test specificity
      of 100% when compared to PCR results. The test sensitivity of monoclonal antibody
      based IHC staining was only 72%, compared to 100% when using the polyclonal
      antibody. CONCLUSION: The most sensitive, readily identified, positively staining
      organs for IHC are the kidney, liver, lung, spleen, and small intestine. Real
      time RT-PCR and IHC staining using a polyclonal antibody on sections of these
      tissues are highly sensitive diagnostic tests for the detection of WNV in
      formalin-fixed tissues of American crows.

PMID- 17537264
TI  - The effect of acetaminophen (four grams a day for three consecutive days) on
      hepatic tests in alcoholic patients--a multicenter randomized study.
AB  - BACKGROUND: Hepatic failure has been associated with reported therapeutic use of
      acetaminophen by alcoholic patients. The highest risk period for alcoholic
      patients is immediately after discontinuation of alcohol intake. This period
      exhibits the largest increase in CYP2E1 induction and lowest glutathione levels.
      Our hypothesis was that common liver tests would be unaffected by administration
      of the maximum recommended daily dosage of acetaminophen for 3 consecutive days
      to newly-abstinent alcoholic subjects. METHODS: Adult alcoholic subjects entering
      two alcohol detoxification centers were enrolled in a prospective double-blind,
      randomized, placebo-controlled trial. Subjects were randomized to acetaminophen,
      4 g/day, or placebo for 3 consecutive days. The study had 95% probability of
      detecting a 15 IU/L difference in serum ALT. RESULTS: A total of 443 subjects
      were enrolled: 308 (258 completed) received acetaminophen and 135 subjects (114
      completed) received placebo. Study groups did not differ in demographics, alcohol
      consumption, nutritional status or baseline laboratory assessments. The peak mean
      ALT activity was 57 +/- 45 IU/L and 55 +/- 48 IU/L in the acetaminophen and
      placebo groups, respectively. Subgroup analyses for subjects presenting with an
      elevated ALT, subjects fulfilling a diagnosis of alcoholic hepatitis and subjects
      attaining a peak ALT greater than 200 IU/L showed no statistical difference
      between the acetaminophen and control groups. The one participant developing an
      increased international normalized ratio was in the placebo group. CONCLUSION:
      Alcoholic patients treated with the maximum recommended daily dose of
      acetaminophen for 3 consecutive days did not develop increases in serum
      transaminase or other measures of liver injury. Treatment of pain or fever for 3
      days with acetaminophen appears safe in newly-abstinent alcoholic patients, such
      as those presenting for acute medical care.

PMID- 17537265
TI  - Acceptability of HIV counselling and testing among tuberculosis patients in south
      Ethiopia.
AB  - BACKGROUND: To benefit from available care and treatment options, patients should
      first be counselled and tested for HIV. Our aim was to assess the acceptability
      of HIV testing among tuberculosis patients under routine care conditions in south
      Ethiopia. METHODS: We interviewed all adult tuberculosis patients who were
      treated at Arba Minch Hospital in Ethiopia between January and August 2005. After
      recording socio-demographic information and tuberculosis treatment history, we
      referred those patients who showed initial willingness to a counsellor for HIV
      counselling and testing. Rapid test methods were used following a pretest
      counselling session. The results were disclosed during a post-test counselling
      session. We used the logistic regression method to assess factors associated with
      willingness and acceptability. RESULTS: 190 adult tuberculosis patients were
      treated at the hospital and all of them consented to take part in the study.
      Their median age was 30 years (range, 15-68) and 52% of them were males. 49
      patients (26%) were previously tested including 29 (59%) HIV positive. Of 161
      patients (excluding the 29 already positive), 118 (73%) were willing to be tested
      and 58% (68/118) of those willing accepted the test. The overall acceptability
      rate was 35% (56/161). Fourteen (20.6%) were HIV positive and women were more
      likely to be HIV infected (p = 0.029). Unemployment and self-perceived high risk
      of HIV infection were associated with initial willingness (OR [95%CI]:2.6 [1.3
      5.5] vs. 5.0 [1.1-22.4], respectively). However, only being unemployed was
      associated with accepting the test (OR = 4.2; 95%CI = 1.9-9.3). CONCLUSION: The
      low acceptability of HIV counselling and testing among tuberculosis patients
      poses a challenge to the scale-up of TB/HIV collaborative efforts. There is a
      need for alternative counselling and testing strategies.

PMID- 17537266
TI  - Requirements and ontology for a G protein-coupled receptor oligomerization
      knowledge base.
AB  - BACKGROUND: G Protein-Coupled Receptors (GPCRs) are a large and diverse family of
      membrane proteins whose members participate in the regulation of most cellular
      and physiological processes and therefore represent key pharmacological targets.
      Although several bioinformatics resources support research on GPCRs, most of
      these have been designed based on the traditional assumption that monomeric GPCRs
      constitute the functional receptor unit. The increase in the frequency and number
      of reports about GPCR dimerization/oligomerization and the implication of
      oligomerization in receptor function makes necessary the ability to store and
      access information about GPCR dimers/oligomers electronically. RESULTS: We
      present here the requirements and ontology (the information scheme to describe
      oligomers and associated concepts and their relationships) for an information
      system that can manage the elements of information needed to describe
      comprehensively the phenomena of both homo- and hetero-oligomerization of GPCRs.
      The comprehensive information management scheme that we plan to use for the
      development of an intuitive and user-friendly GPCR-Oligomerization Knowledge Base
      (GPCR-OKB) is the result of a community dialog involving experimental and
      computational colleagues working on GPCRs. CONCLUSION: Our long term goal is to
      disseminate to the scientific community organized, curated, and detailed
      information about GPCR dimerization/oligomerization and its related structural
      context. This information will be reported as close to the data as possible so
      the user can make his own judgment on the conclusions drawn for a particular
      study. The requirements and ontology described here will facilitate the
      development of future information systems for GPCR oligomers that contain both
      computational and experimental information about GPCR oligomerization. This
      information is freely accessible at http://www.gpcr-okb.org.

PMID- 17537267
TI  - Characterization of N-acetyltransferase 1 and 2 polymorphisms and haplotype
      analysis for inflammatory bowel disease and sporadic colorectal carcinoma.
AB  - BACKGROUND: N-acetyltransferase 1 (NAT1) and 2 (NAT2) are polymorphic isoenzymes
      responsible for the metabolism of numerous drugs and carcinogens. Acetylation
      catalyzed by NAT1 and NAT2 are important in metabolic activation of arylamines to
      electrophilic intermediates that initiate carcinogenesis. Inflammatory bowel
      diseases (IBD) consist of Crohn's disease (CD) and ulcerative colitis (UC), both
      are associated with increased colorectal cancer (CRC) risk. We hypothesized that
      NAT1 and/or NAT2 polymorphisms contribute to the increased cancer evident in IBD.
      METHODS: A case control study was performed with 729 Caucasian participants, 123
      CRC, 201 CD, 167 UC, 15 IBD dysplasia/cancer and 223 controls. NAT1 and NAT2
      genotyping were performed using Taqman based techniques. Eight single nucleotide
      polymorphisms (SNPs) were characterized for NAT1 and 7 SNPs for NAT2. Haplotype
      frequencies were estimated using an Expectation-Maximization (EM) method. Disease
      groups were compared to a control group for the frequencies at each individual
      SNP separately. The same groups were compared for the frequencies of NAT1 and
      NAT2 haplotypes and deduced NAT2 phenotypes. RESULTS: No statistically
      significant differences were found for any comparison. Strong linkage
      disequilibrium was present among both the NAT1 SNPs and the NAT2 SNPs.
      CONCLUSION: This study did not demonstrate an association between NAT1 and NAT2
      polymorphisms and IBD or sporadic CRC, although power calculations indicate this
      study had sufficient sample size to detect differences in frequency as small as
      0.05 to 0.15 depending on SNP or haplotype.

PMID- 17537268
TI  - The impact of health insurance on outpatient utilization and expenditure:
      evidence from one middle-income country using national household survey data.
AB  - BACKGROUND: Achieving universal health insurance coverage by means of different
      types of insurance programs may be a pragmatic and feasible approach. However,
      the fragmentation of the health financing system may imply costs in terms of
      varying ability of the insurance programs to improve access to and reduce
      spending on care across different population groups. This study looks at the
      effect of different types of health insurance programs on the probability of
      utilizing care, the intensity of utilization, and individual spending on care in
      Jordan. METHODS: Using national household survey data collected in 2000 with a
      sub-sample of around 8,300 individuals, the study applies econometric techniques
      to a set of specified models along the two-part model approach to the demand for
      health care. By means of particular tests and other procedures, the robustness of
      the results is controlled. RESULTS: Around 60 percent of the population is
      covered by some type of insurance. However, the distribution varies across income
      groups, and importantly, the effect of insurance on the outcome indicators differ
      substantially across the various programs. Generally, insurance is found to
      increase the intensity of utilization and reduce out-of-pocket spending, while no
      general insurance effect on the probability of use is found. More specifically,
      however, these effects are only found for some programs and not for all. The best
      performing programs are those to which the somewhat better off groups have
      access. CONCLUSION: Notwithstanding the empirical nature of the issues, the
      results point at the need to assess the effect of insurance coverage more
      profoundly than what is commonly done. Applying rigorous analysis to survey data
      in other settings will contribute to bringing out better evidence on what types
      of programs perform most effectively and equitably in different contexts.

PMID- 17537269
TI  - Physiological evaluation of the filamentous fungus Trichoderma reesei in
      production processes by marker gene expression analysis.
AB  - BACKGROUND: Biologically relevant molecular markers can be used in evaluation of
      the physiological state of an organism in biotechnical processes. We monitored at
      high frequency the expression of 34 marker genes in batch, fed-batch and
      continuous cultures of the filamentous fungus Trichoderma reesei by the
      transcriptional analysis method TRAC (TRanscript analysis with the aid of
      Affinity Capture). Expression of specific genes was normalised either with
      respect to biomass or to overall polyA RNA concentration. Expressional variation
      of the genes involved in various process relevant cellular functions, such as
      protein production, growth and stress responses, was related to process
      parameters such as specific growth and production rates and substrate and
      dissolved oxygen concentrations. RESULTS: Gene expression of secreted cellulases
      and recombinant Melanocarpus albomyces laccase predicted the trends in the
      corresponding extracellular enzyme production rates and was highest in a narrow
      "physiological window" in the specific growth rate (micro) range of 0.03-0.05 h
      1. Expression of ribosomal protein mRNAs was consistent with the changes in mu.
      Nine starvation-related genes were found as potential markers for detection of
      insufficient substrate feed for maintaining optimal protein production. For two
      genes induced in anaerobic conditions, increasing transcript levels were measured
      as dissolved oxygen decreased. CONCLUSION: The data obtained by TRAC supported
      the usefulness of focused and intensive transcriptional analysis in monitoring of
      biotechnical processes providing thus tools for process optimisation purposes.

PMID- 17537270
TI  - The use of chilled condensers for the recovery of perfluorocarbon liquid in an
      experimental model of perfluorocarbon vapour loss during neonatal partial liquid
      ventilation.
AB  - BACKGROUND: Perfluorocarbon (PFC) vapour in the expired gases during partial
      liquid ventilation should be prevented from entering the atmosphere and recovered
      for potential reuse. This study aimed to determine how much PFC liquid could be
      recovered using a conventional humidified neonatal ventilator with chilled
      condensers in place of the usual expiratory ventilator circuit and whether PFC
      liquid could be recovered when using the chilled condensers at the ventilator
      exhaust outlet. METHODS: Using a model lung, perfluorocarbon vapour loss during
      humidified partial liquid ventilation of a 3.5 kg infant was approximated. For
      each test 30 mL of FC-77 was infused into the model lung. Condensers were placed
      in the expiratory limb of the ventilator circuit and the amounts of PFC (FC-77)
      and water recovered were measured five times. This was repeated with the
      condensers placed at the ventilator exhaust outlet. RESULTS: When the condensers
      were used as the expiratory limb, the mean (+/- SD) volume of FC77 recovered was
      16.4 mL (+/- 0.18 mL). When the condensers were connected to the ventilator
      exhaust outlet the mean (+/- SD) volume of FC-77 recovered was 7.6 mL (+/- 1.14
      mL). The volume of FC-77 recovered was significantly higher when the condenser
      was used as an expiratory limb. CONCLUSION: Using two series connected condensers
      in the ventilator expiratory line 55% of PFC liquid (FC-77) can be recovered
      during partial liquid ventilation without altering the function of the of the
      ventilator circuit. This volume of PFC recovered was just over twice that
      recovered with the condensers connected to the ventilator exhaust outlet.

PMID- 17537271
TI  - Central administration of dipeptides, beta-alanyl-BCAAs, induces hyperactivity in
      chicks.
AB  - BACKGROUND: Carnosine (beta-alanyl-L-histidine) is a putative neurotransmitter
      and has a possible role in neuron-glia cell interactions. Previously, we reported
      that carnosine induced hyperactivity in chicks when intracerebroventricularly
      (i.c.v.) administered. In the present study, we focused on other beta-alanyl
      dipeptides to determine if they have novel functions. RESULTS: In Experiment 1,
      i.c.v. injection of beta-alanyl-L-leucine, but not beta-alanyl-glycine, induced
      hyperactivity behavior as observed with carnosine. Both carnosine and beta-alanyl
      L-leucine stimulated corticosterone release. Thus, dipeptides of beta-alanyl
      branched chain amino acids were compared in Experiment 2. The i.c.v. injection of
      beta-alanyl-L-isoleucine caused a similar response as beta-alanyl-L-leucine, but
      beta-alanyl-L-valine was somewhat less effective than the other two dipeptides.
      beta-Alanyl-L-leucine strongly stimulated, and the other two dipeptides tended to
      stimulate, corticosterone release. CONCLUSION: These results suggest that central
      beta-alanyl-branched chain amino acid stimulates activity in chicks through the
      hypothalamus-pituitary-adrenal axis. We named beta-alanyl-L-leucine, beta-alanyl
      L-isoleucine and beta-alanyl-L-valine as Excitin-1, Excitin-2 and Excitin-3,
      respectively.

PMID- 17537272
TI  - Towards enhancing national capacity for evidence informed policy and practice in
      falls management: a role for a "Translation Task Group"?
AB  - BACKGROUND: There has been a growing interest over recent years, both within
      Australia and overseas, in enhancing the translation of research into policy and
      practice. As one mechanism to improve the dissemination and uptake of falls
      research into policy and practice and to foster the development of policy
      appropriate research, a "Falls Translation Task Group" was formed as part of an
      NHMRC Population Health Capacity Building grant. This paper reports on the
      group's first initiative to address issues around the research to policy and
      practice interface, and identifies a continuing role for such a group. METHODS: A
      one day forum brought together falls researchers and decision-makers from across
      the nation to facilitate linkage and exchange. Observations of the day's
      proceedings were made by the authors. Participants were asked to complete a
      questionnaire at the commencement of the forum (to ascertain expectations) and at
      its completion (to evaluate the event). Observer notes and the questionnaire
      responses form the basis of analysis. RESULTS: Both researchers and decision
      makers have a desire to bridge the gap between research and policy and practice.
      Significant barriers to research uptake were highlighted and included both
      "health system barriers" (for example, a lack of financial and human resources)
      as well as "evidence barriers" (such as insufficient economic data and
      implementation research). Solutions to some of these barriers included the
      identification of clinical champions within the health sector to enhance evidence
      uptake, and the sourcing of alternative funding to support implementation
      research and encourage partnerships between researchers, decision-makers and
      other stakeholders. CONCLUSION: Participants sought opportunities for ongoing
      networking and collaboration. Two activities have been identified as priorities:
      establishing a "policy-sensitive" research agenda and partnering researchers and
      decision-makers in the process; and establishing a National Translation Task
      Group with a broad membership.

PMID- 17537273
TI  - Quality of life after surgery for benign disease of the parotid gland.
AB  - OBJECTIVE: To evaluate quality of life after surgery for benign neoplastic
      disease of the parotid gland. PATIENTS AND METHODS: A quality of life
      questionnaire, which was created from the Hebrew version of the University of
      Washington Quality of Life prototype, was applied to 55 patients who underwent
      surgery for benign neoplastic parotid disease. All patients were examined in
      Baskent University Adana Teaching and Medical Research Center, where all except
      10 subjects (who responded by phone) completed the quality of life questionnaire.
      RESULTS: The highest overall score was 96.3 indicating no salivary fistula. Only
      one patient complained of salivary secretion through the wound scar. The lowest
      overall score was 59.5 indicating loss of sensation. Although no post-surgical
      pain was reported by 32 (58 per cent) patients, 16 (29 per cent) patients
      reported a post-surgical change in their appearance. Scarring and surgical site
      depression were reported by 26 (47 per cent) and 17 patients (30 per cent),
      respectively. Facial nerve impairment was reported by seven patients (13 per
      cent) during the early post-operative period; these patients recovered from that
      impairment. The only significant statistical correlations were noted between
      general health and gender, and between post-surgical pain and gender. There was
      not any statistical correlation between all data and age, tumour type and
      education level. CONCLUSION: The general status of patients who have undergone
      surgery for a benign parotid neoplasm can be assessed with a quality of life
      questionnaire. Patients' post-surgical quality of life can be improved by the
      correct choice of surgical approach and reconstructive method.

PMID- 17537274
TI  - Is there an association between blood group O and epistaxis?
AB  - INTRODUCTION: Blood group O is associated with lower expression of von Willebrand
      factor suggesting a relative bleeding tendency. A lower admission rate for
      epistaxis among Asians compared with Caucasians has also been noted, with one
      explanation being higher prevalence of blood group O among Caucasians. This study
      investigates whether blood group O is over-represented in patients admitted with
      epistaxis. METHODS: A retrospective study was conducted, using computerised
      hospital in-patient and blood bank databases to identify Caucasians admitted with
      epistaxis between January 2000 and December 2005 inclusive. The control group
      consisted of 500 consecutive patients who had a primary total hip arthroplasty
      and 500 consecutive patients who gave birth within the delivery suite. RESULTS:
      1261 Caucasians admitted with epistaxis were identified. Among epistaxis
      patients, 50.44 per cent were blood group O but among the control group this was
      45.10 per cent (chi-square test p = 0.008). CONCLUSION: Blood group O appears
      over-represented in Caucasian patients admitted with epistaxis, compared with the
      control population, raising the possibility that blood group O is a risk factor
      for epistaxis.

PMID- 17537275
TI  - Angioedema of the airway: an unusual case.
AB  - We report a case of angioedema caused by angiotensin-converting enzyme inhibitor
      and topical lignocaine spray, administered during nasendoscopy. Angioedema
      induced by angiotensin-converting enzyme inhibitors is a rare but well known
      entity. Allergy to topical lignocaine has been acknowledged as a rare phenomenon
      when used for dental surgery and for skin anaesthesia, but it has not previously
      been reported after topical administration prior to nasendoscopy. In the reported
      case, our patient was unfortunate enough to be allergic to both lisinopril and
      lignocaine. The result was life-threatening airway obstruction, and the continued
      use of lignocaine spray sustained the laryngeal oedema. We advise that patients
      are asked about any and every allergy--specifically, any previous problems with
      dental procedures--before administration of local anaesthetic spray to the upper
      aerodigestive tract.

PMID- 17537276
TI  - Education for expectant fathers in workplaces in Turkey.
AB  - Worldwide, there is increasing recognition that if family and reproductive health
      programmes are to be successful, the involvement of men is essential. As part of
      the problem, men also have to be seen as part of the solution. The reality is
      that in many countries, including Turkey, men generally do not accompany their
      partners to health facilities for family planning, antenatal and postnatal
      services and are not expected to attend the labour or birth of their child.
      Workplace programmes are a potential strategy for meeting the reproductive health
      education needs of men in industrial cities such as Istanbul. This intervention
      study was developed to test the feasibility and effects of expanding a special
      programme for expectant fathers to large workplaces in Istanbul, with the aim of
      improving the health of Turkish families during the pregnancy, birth and newborn
      periods. The findings indicate that it is possible to train workplace physicians
      in Istanbul to conduct regular educational programmes for expectant fathers on
      reproductive health, and that such programmes may have beneficial effects,
      especially in the areas of pregnancy nutrition, exclusive breast-feeding, and
      support behaviours. Considering the difficulty of getting men to attend hospital
      or clinic-based educational programmes in large urban areas, bringing such
      training programmes to men at their places of work has the potential to be an
      important strategy. Given that large workplaces in Turkey already have full-time
      physicians charged with the duty of health education for employees, this is also
      a feasible strategy.

PMID- 17537277
TI  - Indian system of medicine and women's health: a clients' perspective.
AB  - India has a strong base of ancient indigenous systems of medicine and its
      national health policies and programmes have consistently promoted the
      integration of Indian Systems of Medicine (ISM) into the country's official
      health system. Realizing the safety and efficacy of ISM drugs, the Department of
      Indian Systems of Medicine and Homoeopathy (ISM&H) has suggested their use for
      certain women's health problems and during pregnancy. Although the Government of
      India has attempted to integrate ISM through the country's contemporary health
      programme of Reproductive and Child Health (RCH), utilization dynamics from the
      clients' perspective is little understood. This study shows that, at least in
      urban areas, for the majority of women's health problems biomedicine is regarded
      as the first choice, failure of which leads clients to seek treatment from ISM as
      a final resort. Nevertheless, women showed a preference for ISM treatment for
      certain specific health problems, strongly backed by a belief in their efficacy.
      Of the predictors that positively influenced women's choice of ISM treatment,
      'strong evidenced-based results' was found to be the most important. Women's
      preference for ISM is dependent on the availability of competent providers.

PMID- 17537278
TI  - Studying health-seeking behaviours: collecting reliable data, conducting
      comprehensive analysis.
AB  - There is certainly a growing need to justify the significance of studying health
      seeking behaviours for designing advocacy campaigns, lobbying for a policy shift
      and convincing donors to invest in priority areas. Moreover, policymakers need to
      be encouraged to design evidence-based policies that take into account
      information relating to health-promoting, -seeking and -utilization behaviour and
      the factors determining these behaviours. This paper primarily covers the
      'methodology' used in the study of health-seeking behaviours and determinants of
      health services utilization in a predominantly rural district of Pakistan. The
      paper substantiates that this methodology is comprehensive and reliable, and
      there is potential for replicating this in similar settings. The approach of
      Kroeger in his research on the study of health-seeking behaviours, particularly
      in developing countries, provides the most holistic framework for examining,
      analysing and interpreting factors and determinants of health-seeking behaviours
      and health services utilization in developing countries. This study endeavoured
      to validate Kroeger's framework in a Pakistani setting, exploring all the factors
      listed through mixed method research, and qualitative supplemented by
      representative quantitative enquiry. This approach has also helped in
      understanding the inter-relationship of various factors and drivers of health
      seeking behaviours from all angles.

PMID- 17537279
TI  - The preference for an additional child among married women in Seoul, Korea.
AB  - South Korea reported a total fertility rate (TFR) of 1.08 in 2005. This is the
      lowest level of all nations in the Organisation for Economic Co-operation and
      Development (OECD). Recently, the decline in the fertility rate has been a
      dominant phenomenon in Korea's major cities. This study investigated the
      relationship between social environmental factors and fertility intentions for
      married women in Seoul, the capital of Korea, using a sample of 2211 married
      women who responded to the Seoul Citizens Health and Social Indicators Survey,
      2005. Here, the effects of selected social environmental characteristics on
      fertility intentions are explored using multivariate logistic regression models.
      The relationships among a woman's age, number of living children, job type,
      housing type, and social group participation were strong indicators of the
      intention to have additional children. Younger women living with fewer children
      generally have a higher intention to have additional children. Among women's job
      types, blue-collar workers have a lower preference for additional children than
      white-collar workers and housewives. Married women participating in social groups
      have a lower preference for additional children than non-participants. Women's
      participation in social activities appears to have various benefits, both
      individually and socially. However, whereas women's participation in economic
      activities has been linked to questions of fertility in previous studies, the
      relationship between fertility and social activities has been downplayed. Women's
      participation in social activities has increased over the past several decades,
      and the trend continues to grow. Therefore, women's participation in social
      activities must be accepted as the status quo, and compatibility between women's
      participation in social activities and childrearing needs to be increased.
      Consequently, a strong foundation for a fertility-friendly environment is needed,
      focusing on blue-collar workers and participation in social activities by married
      women.

PMID- 17537280
TI  - Does staff-patient agreement on needs for care predict a better mental health
      outcome? A 4-year follow-up in a community service.
AB  - BACKGROUND: Patients treated in primary care settings report better mental
      outcomes when they agree with practitioners about the nature of their core
      presenting problems. However, no study has examined the impact of staff-patient
      agreement on treatment outcomes in specialist mental health services. We
      investigated whether a better staff-patient agreement on needs for care predicts
      more favourable outcome in patients receiving community-based psychiatric care.
      METHOD: A 3-month prevalence cohort of 188 patients with the full spectrum of
      psychiatric conditions was assessed at baseline and at 4 years using the
      Camberwell Assessment of Need (CAN), both staff (CAN-S) and patient versions (CAN
      P), and a set of standardized outcome measures. Baseline staff-patient agreement
      on needs was included among predictors of outcome. Both clinician-rated
      (psychopathology, social disability, global functioning) and patient-rated
      (subjective quality of life and satisfaction with services) outcomes were
      considered. RESULTS: Controlling for the effect of sociodemographics, service
      utilization and changes in clinical status, better staff-patient agreement makes
      a significant additional contribution in predicting treatment outcomes not only
      on patient-rated but also on clinician-rated measures. CONCLUSIONS: Mental health
      care should be provided on the basis of a negotiation process involving both
      professionals and service users to ensure effective interventions; every effort
      should be made by services to implement strategies aiming to increase consensus
      between staff and patients.

PMID- 17537281
TI  - Identifying correlates of suicide attempts in suicidal ideators: a population
      based study.
AB  - BACKGROUND: Identification of factors that distinguish between ideators who act
      on their suicidal thoughts from those who do not is an important clinical and
      research objective. METHOD: We examined correlates of suicide attempts in
      suicidal ideators, members of a French-Canadian, school-based cohort. Suicidal
      thoughts were evaluated in adolescence and early adulthood in the total sample of
      suicidal ideators, who were then stratified into subgroups consisting of
      persistent ideators, male ideators and female ideators. RESULTS: In addition to
      persistent suicidal ideas [odds ratios (ORs) 2.1-2.8], Axis I psychopathology,
      female gender and childhood sexual abuse (CSA) were the most consistent
      correlates of suicide attempts. Externalizing disorders were significant
      contributors in persistent ideators [drug misuse: OR 2.8, 95% confidence interval
      (CI) 1.1-6.9] and in male ideators in particular (disruptive disorders: OR 5.9,
      95% CI 2.2-16.0). In women, psychiatric co-morbidity also had a significant
      effect (OR 1.6, 95% CI 1.1-2.1). CSA was of relevance in both women (OR 1.2, 95%
      CI 1.1-1.4) and persistent ideators (OR 1.3, 95% CI 1.1-1.5). Personality traits
      showed gender-specific contribution with affective instability (OR 1.1, 95% CI
      1.01-1.1) and anxiousness (OR 1.3, 95% CI 1.1-1.7) contributing in men and
      disruptive aggression (OR 1.1, 95% CI 1.03-1.3) in women. CONCLUSIONS: Correlates
      of suicide attempts in suicidal ideators vary as a function of the persistence of
      suicidal ideas and gender. This heterogeneity across subgroups of suicidal
      ideators may be attributed, at least in part, to differences between the sexes,
      early environmental adversity, maladaptive personality, and psychiatric symptoms.
      Further exploration and continued prospective follow-up is necessary to examine
      these possibilities.

PMID- 17537282
TI  - Genetic and environmental factors affecting self-esteem from age 14 to 17: a
      longitudinal study of Finnish twins.
AB  - BACKGROUND: We analysed genetic and environmental influences on self-esteem and
      its stability in adolescence. METHOD: Finnish twins born in 1983-1987 were
      assessed by questionnaire at ages 14 (n = 4132 twin individuals) and 17 years (n
      = 3841 twin individuals). Self-esteem was measured using the Rosenberg global
      self-esteem scale and analyzed using quantitative genetic methods for twin data
      in the Mx statistical package. RESULTS: The heritability of self-esteem was 0.62
      [95% confidence interval (CI) 0.56-0.68] in 14-year-old boys and 0.40 (95% CI
      0.26-0.54) in 14-year-old girls, while the corresponding estimates at age 17 were
      0.48 (95% CI 0.39-0.56) and 0.29 (95% CI 0.11-0.45). Rosenberg self-esteem scores
      at ages 14 and 17 were modestly correlated (r = 0.44 in boys, r = 0.46 in girls).
      In boys, the correlation was mainly (82%) due to genetic factors, with residual
      co-variation due to unique environment. In girls, genetic (31%) and common
      environmental (61%) factors largely explained the correlation. CONCLUSIONS: In
      adolescence, self-esteem seems to be differently regulated in boys versus girls.
      A key challenge for future research is to identify environmental influences
      contributing to self-esteem during adolescence and determine how these factors
      interact with genetic influences.

PMID- 17537283
TI  - Attitudes towards childbearing, causal attributions for bipolar disorder and
      psychological distress: a study of families with multiple cases of bipolar
      disorder.
AB  - BACKGROUND: For families with multiple cases of bipolar disorder this study
      explored: attitudes towards childbearing; causal attributions for bipolar
      disorder, in particular the degree to which a genetic model is endorsed and its
      impact on the perceived stigma of bipolar disorder; and predictors of
      psychological distress. METHOD: Two hundred individuals (95 unaffected and 105
      affected with either bipolar disorder, schizo-affective disorder - manic type, or
      recurrent major disorder) were surveyed, using mailed, self-administered
      questionnaires. RESULTS: Thirty-five (35%) participants reported being 'not at
      all willing to have children' or 'less willing to have children' as a result of
      having a strong family history of bipolar disorder. Being not at all or less
      willing to have children was associated with perceived stigma of bipolar disorder
      [odds ratio (OR) 2.42, p = 0.002], endorsement of a genetic model (OR 1.76, p =
      0.046), and being affected (OR 2.16, p = 0.01). Among unaffected participants
      only, endorsement of a genetic model was strongly correlated with perceived
      stigma (rs = 0.30, p = 0.004). Perceiving the family environment as an important
      factor in causing bipolar disorder was significantly associated with
      psychological distress (OR 1.58, p = 0.043) among unaffected participants. Among
      affected participants, perceived stigma was significantly correlated with
      psychological distress (OR 2.44, p = 0.02), controlling for severity of symptoms
      (p < 0.001). CONCLUSIONS: Having a genetic explanation for bipolar disorder may
      exacerbate associative stigma among unaffected members from families with
      multiple cases of bipolar disorder, while it does not impact on perceived stigma
      among affected family members. Affected family members may benefit from
      interventions to ameliorate the adverse effects of perceived stigma.

PMID- 17537285
TI  - Clinical and prognostic implications of seasonal pattern in bipolar disorder: a
      10-year follow-up of 302 patients.
AB  - BACKGROUND: More than 20% of bipolar patients may present with seasonal pattern
      (SP). Seasonality can alter the course of bipolar disorder. However, to date,
      long-term follow-up studies of bipolar patients presenting with SP are scarce. We
      present a 10-year follow-up study comparing clinical and demographic features of
      bipolar patients with and without SP. METHOD: Three hundred and twenty-five
      bipolar I and II patients were followed up for at least 10 years. SP was defined
      according to DSM-IV criteria. Clinical variables were obtained from structured
      interviews with the patients and their relatives. Patients with and without SP
      were compared regarding clinical and sociodemographic variables and a stepwise
      logistic regression was performed. RESULTS: Seventy-seven patients (25.5%) were
      classified as presenting with SP, while 225 (74.5%) were considered as presenting
      with no significant seasonal variation. Twenty-three patients (7%) were excluded
      from the study because it was unclear whether they had seasonality or not. There
      were no differences between groups regarding demographic variables. Patients with
      SP predominantly presented with bipolar II disorder, depressive onset, and
      depressive predominant polarity. The greater burden of depression did not
      correlate with indirect indicators of severity, such as suicidality,
      hospitalizations or psychotic symptoms. CONCLUSIONS: Our study links the presence
      of SP with both bipolar II disorder and predominant depressive component.
      However, we could not find any difference regarding functionality or
      hospitalization rates. Modifications in the criteria to define SP are suggested
      for a better understanding of bipolar disorder.

PMID- 17537284
TI  - Reaction time performance in ADHD: improvement under fast-incentive condition and
      familial effects.
AB  - BACKGROUND: Reaction time (RT) variability is one of the strongest findings to
      emerge in cognitive-experimental research of attention deficit hyperactivity
      disorder (ADHD). We set out to confirm the association between ADHD and slow and
      variable RTs and investigate the degree to which RT performance improves under
      fast event rate and incentives. Using a group familial correlation approach, we
      tested the hypothesis that there are shared familial effects on RT performance
      and ADHD. METHOD: A total of 144 ADHD combined-type probands, 125 siblings of the
      ADHD probands and 60 control participants, ages 6-18, performed a four-choice RT
      task with baseline and fast-incentive conditions. RESULTS: ADHD was associated
      with slow and variable RTs, and with greater improvement in speed and RT
      variability from baseline to fast-incentive condition. RT performance showed
      shared familial influences with ADHD. Under the assumption that the familial
      effects represent genetic influences, the proportion of the phenotypic
      correlation due to shared familial influences was estimated as 60-70%.
      CONCLUSIONS: The data are inconsistent with models that consider RT variability
      as reflecting a stable cognitive deficit in ADHD, but instead emphasize the
      extent to which energetic or motivational factors can have a greater effect on RT
      performance in ADHD. The findings support the role of RT variability as an
      endophenotype mediating the link between genes and ADHD.

PMID- 17537286
TI  - Feeling the pressure: work stress and mental health.

PMID- 17537287
TI  - Actuarial prediction of violent recidivism in mentally disordered offenders.
AB  - BACKGROUND: Actuarial instruments may be useful in predicting long-term violence
      in mentally disordered patients. We compared two instruments that differ in terms
      of what they are designed to predict (general versus violent recividism) and the
      inclusion of stable mental health variables. METHOD: A large sample of mentally
      disordered patients were scored on two risk assessment instruments, the Violence
      Risk Appraisal Guide (VRAG) and the Offender Group Reconviction Scale (OGRS),
      based on information at the point of discharge. Their criminal histories for at
      least 2 years following discharge were obtained from official records. RESULTS:
      Both instruments were good predictors of both violent and general offending. Over
      shorter periods (0.85], which were significantly better than the OGRS. For longer
      follow-up periods the instruments had approximately equal prediction accuracy.
      However, both instruments predicted far more offences than were in fact recorded.
      CONCLUSIONS: The VRAG is a very good predictor of future violence in the UK
      sample. The OGRS may also be of value as it can be completed quickly and without
      the need for mental health variables. Caution is needed, however, as both
      instruments appeared to over-predict the levels of reconvictions in this sample.

PMID- 17537288
TI  - Effects of miglitol, an alpha-glucosidase inhibitor, on glycaemic status and
      histopathological changes in islets in non-obese, non-insulin-dependent diabetic
      Goto-Kakizaki rats.
AB  - Miglitol, a 1-deoxynojirimycin derivative, is an alpha-glucosidase inhibitor. In
      the present study, the effects of acute (single-dose) and chronic (8-week) oral
      administration of miglitol in Goto-Kakizaki (GK) rats, an animal model of type 2
      diabetes, were investigated. Dose-dependent decreases in incremental blood
      glucose concentrations integrated over a period of 2 h (deltaAUC0-2 h) for values
      of blood glucose after sucrose-loading in miglitol-treated GK rats were observed
      following an acute oral administration of miglitol (1, 3 or 10 mg/kg body
      weight). At 10 mg/kg, the deltaAUC0-2 h of blood glucose was decreased by 45 %
      compared with the control group. Following the oral administration of miglitol in
      a dietary mixture (10 mg, 20 mg or 40 mg miglitol/100 g control diet) for 8
      weeks, the ratio of HbA1c at 8 weeks compared with 0 weeks in GK rats treated
      with 40 mg miglitol/100 g control diet miglitol was significantly decreased
      compared with control GK rats without changes in body weight. In oral glucose
      tolerance testing, miglitol caused a slight decrease in the deltaAUC0-2 h of
      plasma glucose concentration. In addition, miglitol treatment slightly inhibited
      the reduction in beta-cell mass, and lessened the irregular contours and fibrosis
      of the islets in GK rats. These results indicate that miglitol ameliorates the
      hyperglycaemic state of GK rats and the impaired function of the pancreatic
      islets, as well as preventing the degeneration of islets in GK rats.

PMID- 17537289
TI  - The association of betaine, homocysteine and related metabolites with cognitive
      function in Dutch elderly people.
AB  - The importance of the one-carbon metabolites, choline and homocysteine, to brain
      function is well known. However, the associations between the one-carbon
      metabolites choline, betaine, methionine and dimethylglycine with cognition in
      elderly are unclear. We therefore examined the associations of these metabolites
      with cognition in a double-blind, placebo-controlled trial. Individuals (n 195)
      were randomized to receive daily oral capsules with either 1000 microg cobalamin
      (vitamin B12), or 1000 microg cobalamin plus 400 microg folic acid, or placebo
      for 24 weeks. Concentrations of homocysteine, methionine, choline, betaine and
      dimethylglycine were assessed before and after 12 and 24 weeks of treatment.
      Cognitive function, including domains of attention, construction, sensomotor
      speed, memory and executive function, was assessed before and after 24 weeks of
      treatment. At baseline, elevated plasma homocysteine was associated with lower
      performance of attention, construction, sensomotor speed and executive function.
      In addition, betaine was positively associated with better performance of
      construction, sensomotor speed and executive function, whereas elevated
      concentrations of methionine were positively associated with sensomotor speed.
      Daily combined supplementation with cobalamin plus folic acid decreased total
      homocysteine concentrations by 36%, and increased betaine concentrations by 38%.
      Participants with the largest increases in betaine concentrations showed a
      borderline significant (P = 0.07) higher memory performance compared to those
      without it. Although this trial observed associations of homocysteine and betaine
      with cognitive domains prior to supplementation, decreased concentrations of
      homocysteine were not related to improved cognitive performance. There was a
      tendency of participants with the largest increases in betaine concentrations to
      show the greatest improvement in memory function.

PMID- 17537290
TI  - Fish intake, mercury, long-chain n-3 polyunsaturated fatty acids and risk of
      stroke in northern Sweden.
AB  - Results of previous studies on fish intake and stroke risk have been
      inconclusive. Different stroke types have often not been separated. Our aim was
      to elucidate whether intake of fish, Hg or the sum of proportions of fatty acids
      EPA (20 : 5n-3) and DHA (22 : 6n-3) influence the risk of haemorrhagic or
      ischaemic stroke. Within a population-based cohort from a community intervention
      programme, 369 stroke cases and 738 matched controls were identified and included
      in the present nested case-control study. Information on fish intake had been
      recorded at recruitment, i.e. before diagnosis. Hg levels were determined in
      erythrocyte membranes, also collected at recruitment, and the relative content of
      fatty acids was measured in erythrocyte membranes or plasma phospholipids. The
      results showed that in women there was a non-significant decrease in stroke risk
      with increasing fish intake (OR 0.90 (95 % CI 0.73, 1.11) per meal per week). The
      risk in women differed significantly (P = 0.03) from that in men, in whom the OR
      for stroke rose with increasing fish intake (OR 1.24 (95 % CI 1.01, 1.51) per
      meal per week). The corresponding risk in men for Hg was 0.99 (95 % CI 0.93,
      1.06), and for the sum of proportions of EPA and DHA 1.08 (95 % CI 0.92, 1.28).
      We conclude that the relationship between stroke risk and fish intake seems to be
      different in men and women. Increased levels of EPA and DHA do not decrease the
      risk for stroke and there is no association between stroke risk and Hg at these
      low levels.

PMID- 17537291
TI  - The time of day and the proportions of macronutrients eaten are related to total
      daily food intake.
AB  - Intake in the morning is particularly satiating and associated with lower total
      amounts ingested for the day while intake at night is associated with greater
      overall daily intake. But, the influence of carbohydrates, fats or proteins
      ingested at various times of the day is unknown. The intakes of 375 male and 492
      female free-living individuals that were acquired with 7 d diet-diary reports
      were reanalysed. The intakes of carbohydrates, fats and proteins, and the density
      of intake occurring during three 6 h periods (06.00 to 11.59 hours (morning),
      12.00 to 17.59 hours (afternoon) and 18.00 to 23.59 hours (evening)) were
      identified and related to overall daily and meal intakes. Energy density of
      intake during all periods was found to be positively related to overall intake.
      When the proportion of daily carbohydrate ingested in the morning was high, less
      total food energy and carbohydrate were ingested over the entire day. When the
      proportion of daily fat ingested in the morning was high, less total food energy
      and carbohydrate and fat were ingested over the entire day. When the proportion
      of daily protein ingested in the morning was high, less protein was ingested over
      the entire day. Conversely, when intake was relatively high in the evening of
      either total food energy, carbohydrate or fat, then overall daily energy intakes
      tended to be higher. The results suggest that the morning intake association with
      reduced total intake is macronutrient specific, with morning carbohydrate, fat
      and protein intake associated with reduced daily carbohydrate, fat and protein
      intake, respectively.

PMID- 17537292
TI  - Sex differences in prevalence of anaemia and iron deficiency in infancy in a
      large multi-country trial in South-East Asia.
AB  - To evaluate effects of Fe supplementation and sex on the prevalence of anaemia
      and Fe status in infants in South-East Asia, biochemical data from four parallel,
      randomized, double-blind trials with Fe and/or Zn supplementation in infants (n
      2452) in Indonesia, Thailand and Vietnam was pooled. At recruitment (5 months of
      age), Hb concentrations were slightly but significantly lower in boy infants
      compared with girl infants (108.7 g/l v. 111.4 g/l, P = 0.04). At 11 months of
      age, boy infants not receiving Fe had significantly lower Hb (106.2 g/l v. 111.0
      g/l, P < 0.001) and lower serum ferritin concentrations (14.3 microg/l v. 21.1
      g/l, P < 0.001) than girl infants not receiving Fe. Consequently, boy infants had
      a relative risk of 1.6 (95% CI 1.3, 2.1) to be anaemic, and of 3.3 (95% CI 2.1,
      5.0) for having Fe deficiency anaemia compared with girl infants. Fe
      supplementation significantly increased Hb concentrations in both boys and girls.
      There was no sex difference in Fe status in infants receiving Fe for 6 months.
      This study shows that the markedly higher risk for anaemia and Fe deficiency
      indicates higher Fe requirements in boy than in girl infants. In South-East Asia,
      standard infant feeding practices do not provide sufficient Fe to meet
      requirements of infants, especially boys. Current daily recommended intake for Fe
      in infancy is the same for boy and girl infants however. Our findings suggest
      that in especially the second half of infancy, Fe requirements for boy infants
      are approximately 0.9 mg/d higher than for girl infants.

PMID- 17537293
TI  - 25-hydroxyvitamin D3 affects vitamin D status similar to vitamin D3 in pigs--but
      the meat produced has a lower content of vitamin D.
AB  - In food databases, the specific contents of vitamin D3 and 25-hydroxyvitamin D3
      in food have been implemented in the last 10 years. No consensus has yet been
      established on the relative activity between the components. Therefore, the
      objective of the present study was to assess the relative activity of 25
      hydroxyvitamin D3 compared to vitamin D3. The design was a parallel study in pigs
      (n 24), which from an age of 12 weeks until slaughter 11 weeks later were fed
      approximately 55 microg vitamin D/d, as vitamin D3, in a mixture of vitamin D3
      and 25-hydroxyvitamin D3, or 25-hydroxyvitamin D3. The end-points measured were
      plasma 25-hydroxyvitamin D3, and in the liver and loin the content of vitamin D3
      and 25-hydroxyvitamin D3. Vitamin D3 and 25-hydroxyvitamin D3 in the feed did not
      affect 25-hydroxyvitamin D3 in the plasma, liver or loin differently, while a
      significant effect was shown on vitamin D3 in the liver and loin (P < 0.001). 25
      Hydroxyvitamin D3 in the plasma, liver and loin significantly correlates with the
      sum of vitamin D3 and 25-hydroxyvitamin D3 in the feed (P < 0.05). Therefore, 25
      hydroxyvitamin D3 should be regarded as having the same activity as vitamin D3 in
      food databases. Sole use of 25-hydroxyvitamin D3 as a vitamin D source in pig
      feed will produce liver and meat with a negligible content of vitamin D3, while
      an increased content of vitamin D3 in the feed will produce liver and meat with
      increased content of both vitamin D3 and 25-hydroxyvitamin D3.

PMID- 17537294
TI  - Increased plant sterol and stanol levels in brain of Watanabe rabbits fed
      rapeseed oil derived plant sterol or stanol esters.
AB  - Foods containing plant sterol or stanol esters can be beneficial in lowering LDL
      cholesterol concentration, a major risk factor for CVD. The present study
      examined whether high dietary intake of rapeseed oil (RSO) derived plant sterol
      and stanol esters is associated with increased levels of these components in
      brain tissue of homozygous and heterozygous Watanabe rabbits, an animal model for
      familial hypercholesterolemia. Homozygous animals received either a standard
      diet, RSO stanol or RSO sterol ester while heterozygous animals were additionally
      fed with 2 g cholesterol/kg to the respective diet form for 120 d (n 9 for each
      group). Concentrations of cholesterol, its precursor lathosterol, plant sterols
      and stanols in brain and additionally in liver and plasma were determined by
      highly sensitive GC-MS. High-dose intake of RSO derived plant sterols and stanols
      resulted in increased levels of these components in plasma and liver. In brain a
      limited uptake of plant sterols and stanols was proven, indicating that these
      compounds passed the blood-brain barrier and may be retained in the brain tissue
      of Watanabe rabbits. Plant stanol ester feeding lowered plant sterol levels in
      brain, liver, and plasma. Cholesterol synthesis in brain, indicated by
      lathosterol, a local surrogate cholesterol synthesis marker, does not seem to be
      affected by plant sterol or stanol ester feeding. We conclude that high dose
      intake of plant sterol and stanol esters in Watanabe rabbits results in elevated
      concentrations of these components not only in the periphery but also in the
      central nervous system.

PMID- 17537295
TI  - [Ponderation and expectation on several obstetric issues].

PMID- 17537296
TI  - [Third meeting of the popular and important problems on obstetrics and the second
      obstetrics directors' forum].

PMID- 17537297
TI  - [Clinical study of selective multifetal pregnancy reduction in second trimester].
AB  - OBJECTIVE: To investigate the operative indication, timing, method, selective
      standards of feticided fetus and the number of reduced fetuses of selective
      multifetal pregnancy reduction in second trimester, and the pregnancy outcome of
      multifetal pregnancy by this operation. METHODS: Trans-abdominal selective
      multifetal pregnancy reductions in 37 cases of multiple pregnancy (twins 6 cases,
      triplets 21 cases, quadruplets 8 cases, and quintuplets 2 cases) during 12(+1) -
      25 weeks were performed under ultrasound guidance. The fetus to be reduced was
      injected potassium chloride (KCl) intracardiacally until the fetal heartbeat
      stopped gradually. Totally 46 fetuses were reduced. Periodic prenatal examination
      and monitoring of coagulation function were carried out after the procedure. The
      pregnancy complications and pregnancy outcome of all cases were recorded.
      RESULTS: (1) The successful ratio of reduction was 100% (46/46 fetuses) and the
      successful pregnancy ratio was 88.9% (24/27). (2)Among all the 37 cases, fifteen
      delivered after 36 weeks, seven delivered in 32 - 36 weeks, three delivered in 28
      - 32 weeks, two aborted after feticide, and ten cases were in pregnancy at the
      time of this study. The mean gestational age of all was (34.9 +/- 4.1) weeks, and
      the delivery ratio after 28 weeks was 92.6% (25/27). (3) The mean birth weight of
      singletons was (3014 +/- 640) g, and of twins was (2557 +/- 573) g. The neonates
      of three triplets all died except for in one case two fetuses were alive. (4)
      Except in two cases after reducing one fetus of monoamniotic twins, another one
      died within 24 hours, the remaining fetuses were all alive. (5) Pre-eclampsia
      occurred in three cases. None of the cases had blood coagulation disturbances.
      CONCLUSION: (1) Selective multifetal pregnancy reduction in second trimester can
      feticide the abnormal fetus objectively or reduce the fetal number effectively.
      It is a safe procedure to decrease the complications of multifetal pregnancy and
      increase the birth weight. (2) If the intention is reducing the fetal number, we
      choose the fetus who lies in the fundus uteri and reduce the multifetal pregnancy
      to twins. (3) It is advised to aviod performing the procedure during vaginal
      bleeding. We reduce fetus after vaginal bleeding stops for one or more weeks. (4)
      Selective second-trimester multifetal pregnancy reduction will not result in the
      disturbance of blood coagulation and the death of remaining fetus. The incidence
      of pre-eclampsia is decreased after multifetal pregnancy reduction.

PMID- 17537298
TI  - [Clinical analysis of hypothyroidism during pregnancy].
AB  - OBJECTIVE: To investigate the incidence, treatment and pregnant outcomes of women
      with hypothyroidism during pregnancy. METHODS: A retrospective analysis was
      conducted on the perinatal care, treatment and pregnant outcomes of 31 pregnant
      women with hypothyroidism from Jan.1995 to May.2006 in our hospital. All subjects
      were received in the high risk clinic, and the thyroid function was monitored
      every 1.0 - 1.5 months. The dosage of LT4 was adjusted to maintain the normal
      level of thyroid function. RESULTS: The incidence of maternal hypothyroidism
      during the study period was 1.27 per thousand (31/24 327) [0.19 per thousand
      (1/5251) - 2.32 per thousand (15/6456)]. The average LT4 dosage in pre-gestation,
      the first, second, third trimester and postpartum was (33 +/- 35), (51 +/- 36),
      (68 +/- 42), (76 +/- 42) and (38 +/- 34) microg/d, respectively. Compared with
      the pre-gestational period, the dosage in the first trimester or postpartum was
      higher although the difference was not significant (P>0.05). The required dose of
      LT4 during the second and third trimester was respectively, remarkably increased
      compared to pre-gestational period (P<0.05). The average increase of the dose of
      LT4 required during the pregnancies was about 35%. All of 31 women had uneventful
      pregnancies. No perinatal mortality or congenital hypothyroidism occurred. The
      incidence of abnormal glucose metabolism was up to 16.1%. CONCLUSIONS: The
      incidence of maternal hypothyroidism is increasing yearly. It is of great value
      in improving the pregnant outcome through adjusting the LT4 dose during pregnancy
      and close monitoring of maternal and fetal status.

PMID- 17537299
TI  - [Predictive value of soluble vascular endothelial growth factor receptor 1 for
      preeclampsia in second-trimester].
AB  - OBJECTIVE: To evaluate the predictive value of plasma levels of soluble vascular
      endothelial growth factor receptor 1 (VEGFR-1, also known as sFlt-1) in second
      trimester for preeclampsia. METHODS: One hundred and forty-six pregnant women
      with normal blood pressure previously were prospectively included in the study.
      Peripheral venous blood samples were obtained between 20 and 26 gestational
      weeks. Plasma levels of sFlt-1 were measured by an enzyme-linked immunoassay.
      RESULTS: (1) Among 146 previously normotensive women, 12 developed preeclampsia
      (preeclampsia group), 134 remained normal pregnant till the end (normal group).
      (2) The plasma levels of sFlt-1 in preeclampsia group [(4135 +/- 699) ng/L] was
      significantly higher than that in normal group [(1490 +/- 1033) ng/L] (P<0.01).
      The increase in sFlt-1 occurred approximately 10 weeks before the diagnosis of
      preeclampsia. (3) The best cut-off values for preeclampsia of sFlt-1 was 3344
      ng/L, the area under the curve was 0.981, the sensitivity, specificity, positive
      predictive value, and negative predictive value of sFlt-1 in predicting
      preeclampsia were 100%, 96%, 67%, and 100%, respectively. CONCLUSION: The
      maternal plasma levels of sFlt-1 in women with preeclampsia are higher than that
      in normal pregnant women and may be used as an earlier predictor for
      identification of patients at risk for preeclampsia.

PMID- 17537300
TI  - [Relationship between pain symptoms and clinico-pathological features of pelvic
      endometriosis].
AB  - OBJECTIVE: To study the relationship between pain symptoms and the clinico
      pathological features of pelvic endometriosis (EM). METHODS: One hundred thirty
      patients with laparoscopic diagnosis of EM were studied retrospectively and the
      relationship between pain symptoms including dysmenorrhea, chronic pelvic pain
      (CPP), dyspareunia and dyschezia and the anatomical features of pelvic
      endometriosis were evaluated. RESULTS: One hundred (76.9%) patients with pain
      symptoms and 30 (23.1%) without were included in this study. The number of
      patients with mild, moderate and severe dysmenorrhoea was 27 (20.8%), 41 (31.5%),
      and 32 (24.6%), respectively. Patients with dyspareunia, CPP and dyschezia were
      46 (35.4%), 45 (34.6%) and 67 (51.5%), respectively. Compared with patients
      without dysmenorrhea, the proportion of deep utero-sacral nodules (45.0% vs
      13.3%, P=0.00), recto-vaginal nodules (16.0% vs 0, P=0.01), complete obliteration
      of cul-de sac (41.0% vs 10.0%, P=0.00), and lesions of DIE (51.0% vs 16.7%,
      P=0.00) was significantly increased in patients with dysmenorrhea. The severity
      of dysmenorrhea was positively correlated with nodules in uterosacral ligaments
      (P=0.005, r=0.302), and invasive depth of uterosacral ligaments (P=0.016,
      OR=5.085). Among patients with endometrioma, significantly more moderate to
      severe adhesions were found in patients with dysmenorrhea, compared with those
      patients without dysmenorrhea (29.1% vs 8.3%, P=0.029). Patients with CPP had
      more nodules in the utero-sacral ligaments (51.1% vs 30.6%, P=0.018) and DIE
      lesions (57.8% vs 35.3%, P=0.011), compared with those without. More nodules in
      the utero-sacral ligaments (46.3% vs 28.6%, P=0.028), recto-vaginal nodules
      (19.4% vs 4.8%, P=0.01), complete obliteration of cul-de sac (44.8% vs 22.2%,
      P=0.005) and DIE lesions (53.7% vs 31.7%, P=0.01) were found in patients with
      dyschezia, compared with those without. Nodules in the recto-vaginal pouch were
      an independent risk factor of dyspareunia. CONCLUSION: Pain symptoms including
      dysmenorrhea, dyspareunia, chronic pelvic pain, and dyschezia are remarkably
      related to endometriotic nodules at the posterior part of the pelvis or those
      with deep invasions.

PMID- 17537301
TI  - [Comparison of different antidepression therapy in perimenopausal and
      postmenopausal women with depression].
AB  - OBJECTIVE: To study the effects of antidepression drugs and hormone replacement
      therapy (HRT) in perimenopausal and postmenopausal women with depression.
      METHODS: Eighty six perimenopausal and postmenopausal women with depression were
      divided into two groups, and treated for 12 weeks, respectively. Forty three
      received antidepression drugs as control group. Among them, mild to moderate
      depression were treated with deanxid (1 - 2 pills/d), and severe depression with
      fluoxetine (20 mg/d). Another 43 took Tibolone (livial) as HRT group (1.25 mg/d).
      All patients were assessed with the Hamilton depression rating scale for
      depression (HRSD) and self rating depression scale (SDS) before and at weeks 4,
      8, 12 after treatment. RESULTS: (1) Total effective rate of control and HRT
      groups was 96% and 93%, respectively, in mild-moderate depression (chi(2)=0.012,
      P>0.05), while there was a significant difference between two groups in severe
      depression. The overall effective rates were 93% (control group) and 42% (HRT
      group), respectively (chi(2) = 5.72, P < 0.01). (2) HRSD of mild-moderate
      depression was 26.8 +/- 5.7, 10.7 +/- 3.6, 6.4 +/- 3.6, 3.5 +/- 2.5, respectively
      in control group, and were 25.3 +/- 4.7, 15.2 +/- 5.3, 11.4 +/- 4.4, 4.4 +/- 3.8
      in HRT group before and at weeks 4, 8, and 12 after treatment. There was no
      difference between two groups at weeks 0, and 12 after treatment (P>0.05). HRSD
      scores of severe depression were 37.6 +/- 5.6, 21.4 +/- 5.2, 14.2 +/- 4.2, 7.3 +/
      2.3, respectively, in control group, and were 38.2 +/- 4.8, 32.6 +/- 5.4, 28.2
      +/- 4.6, 24.3 +/- 4.5, respectively, in HRT group before and at weeks 4, 8, and
      12 after treatment. There was no difference in HRSD before treatment (P>0.05),
      but a significant difference at weeks 4, 8, and 12 between two groups (P<0.01).
      (3) SDS of mild and moderate as well as severe depression was significantly
      different at weeks 0, 4.8, and 12 in control group (P<0.01), while there was a
      difference in SDS of severe depression before treatment and at weeks 12 in HRT
      group (P<0.05). A significant reduction in HRSD and SDS of severe depression was
      demonstrated in control group than in HRT group (P<0.01) CONCLUSION:
      Antidepression drugs and HRT can improve symptoms of depression in perimenopausal
      and postmenopausal women, but the effect of antidepression drugs is much better
      than HRT, especially in severe depression.

PMID- 17537302
TI  - [Clinical analysis of conversion from gynecological laparoscopic surgery to
      laparotomy].
AB  - OBJECTIVE: To discuss the causes and clinical significance of conversion to
      laparotomy during laparoscopic surgery. METHOD: Three thousand two hundred and
      three cases who underwent laparoscopic surgery during the past five years were
      analyzed retrospectively. RESULTS: Three thousand one hundred and eighty cases
      underwent laparoscopic surgery, in which 23 cases were converted to laparotomy
      due to factors including severe pelvic adhesions (6 cases), complex disease with
      difficulties in laparoscopy (7 cases), massive haemorrhage (3 cases), bladder
      trauma (1 case), gastric trauma (1 case), intestinal trauma (1 case), as well as
      unexpected malignant genitalia neoplasm (4 cases). CONCLUSION: The major causes
      for the conversion to laparotomy during gynecology laparoscopic surgery are
      severe pelvic adhesion and complex disease with difficulties in laparoscopy.
      Careful evaluation before surgery and conversion to laparotomy at the right
      moment can decrease the complication.

PMID- 17537303
TI  - [The measurement of proportion and function of regulatory T cells in unexplained
      recurrent spontaneous abortion].
AB  - OBJECTIVE: To investigate the proportion and function of CD(4)(+)CD(25)(+)
      regulatory T cells (CD(4)(+)CD(25)(+) Tr) in unexplained recurrent spontaneous
      abortion (URSA). METHODS: (1) Proportion measurement: the proportion of
      CD(4)(+)CD(25)(+) Tr cells in peripheral blood was measured by double-label flow
      cytometric analysis. The samples were taken from 15 URSA women, 15 normal non
      pregnancy women and 13 normal pregnancy women. (2) Function measurement:
      CD(4)(+)CD(25)(+) Tr cells and CD(4)(+)CD(25)(-) T cells were extracted from
      peripheral blood lymphocytes by the microbeads separation. The purity of
      CD(4)(+)CD(25)(+) Tr cells and CD(4)(+)CD(25)(-) T cells was measured by flow
      cytometry. The growth inhibitory effect of CD(4)(+)CD(25)(+) Tr cells on
      CD(4)(+)CD(25)(-) T cells was assessed in vitro. RESULTS: The proportion of
      CD(4)(+)CD(25)(+) Tr cells was decreased significantly in URSA women (6.9 +/-
      1.8)% than that in normal non-pregnancy women [(10.8 +/- 1.1)%] (P<0.05) and
      normal pregnancy women [(11.2 +/- 1.4)%] (P<0.01). Moreover, the suppressive rate
      of CD(4)(+)CD(25)(+) Tr cells was decreased significantly in URSA women (75 +/-
      6)% than that in normal non-pregnancy women [(89 +/- 4)%] (P<0.05) and normal
      pregnancy women [(90 +/- 4)%] (P<0.01). However, with respect to the proportion
      and function of CD(4)(+)CD(25)(+) Tr cells, there was no significant difference
      between normal non-pregnancy women and normal pregnancy women (P > 0.05).
      CONCLUSION: The results suggest that decrease in proportion and function of
      CD(4)(+)CD(25)(+) Tr cells may be associated with URSA.

PMID- 17537304
TI  - [Relationship between three thrombophilic gene mutations and unexplained
      recurrent early spontaneous abortion].
AB  - OBJECTIVE: To explore the relationship of methylenetetrahydrofolate reductase
      (MTHFR) gene C677T, factor V (FV) gene G1691A and prothrombin (PT) gene G20210A
      polymorphisms to unexplained recurrent early spontaneous abortion (URESA).
      METHODS: One hundred and twelve patients with URESA and 100 women with at least 1
      normal pregnancy and without any miscarriage were analyzed for MTHFR, FV and PT
      gene polymorphisms by polymerase chain reaction-restriction fragment length
      polymorphism (PCR-RFLP). RESULTS: MTHFR gene T/T genotype and T allele
      frequencies were increased in URESA patients [38.4% (43/112) and 59.8% (134/224)]
      versus controls [18.0% (18/100) and 43% (43/100), P<0.01]. The patients carrying
      T/T genotype had a high risk of URESA (OR=2.8390, 95% CI: 1.5022 - 5.3661).
      However, FV and PT G20210A mutations were not found either in patients or in
      controls. CONCLUSIONS: The genetic polymorphisms of MTHFR C677T are associated
      with URESA. It might indicate a genetic influence on pathogenesis of URESA. FV
      and PT gene mutations may be rare in Chinese women, and have no significance in
      URESA.

PMID- 17537305
TI  - [Homocysteine decreases the invasion in cultured human trophoblasts: relationship
      between homocysteine and matrix metalloproteinase-2, -9 expression].
AB  - OBJECTIVE: To test the hypothesis that homocysteine can decrease MMP-2 and MMP-9
      expression in cultured trophoblasts of early pregnancy and that homocysteine can
      prevent trophoblasts invasion in the early stage of preeclampsia. METHODS:
      Cytotrophoblasts from early pregnancy were isolated and cultured. Trophoblasts
      were treated with or without Hcy (1 mmol/L) for 48 hour, and real time RT-PCR and
      gelatin zymography were used to quantify the mRNA and protease activity of MMP-2,
      -9. RESULTS: Treatment with Hcy (1 mmol/L) induced a decrease in MMP-2 mRNA by
      21% and MMP-9 mRNA by 11%. At protein level MMP-2 expression decreased 14% and
      MMP-9 expression decreased 52% compared with control. CONCLUSIONS: Homocysteine
      can decrease MMP-2, -9 expression in trophoblasts of early pregnancy and
      influence its invasion process.

PMID- 17537306
TI  - [Identification of differentially expressed genes in endometrium during the
      window of implantation using suppression substractive hybridization].
AB  - OBJECTIVE: To identify genes differentially expressed in the window of
      implantation and explore the molecular basis of the development of endometrial
      receptivity. METHODS: A subtracted cDNA library of the window of implantation was
      constructed by suppression subtractive hybridization (SSH) method. The screened
      clones of the subtracted library were sequenced and GenBank homology search was
      performed. The differential expression of ribosomal protein (RP) L7, RPL7
      pseudogene (RPL7p), RPL19 and tyrosine 3-monooxygenase/tryptophan 5-monooxygenase
      activation protein zeta polypeptide (YWHAZ) were further confirmed by RT-PCR.
      RESULTS: After sequencing and GenBank homology search of 50 clones, 35
      differentially expressed genes were detected in the window of implantation, of
      which 23 were known genes, and 12 were unknown genes. Some of the known genes
      have been proved to be associated with implantation, while others were firstly
      screened out by us. The results of RT-PCR confirmed that RPL7, RPL7p, RPL19 and
      YWHAZ were highly expressed in the window of implantation, 0.75 +/- 0.21, 1.72 +/
      0.30, 1.23 +/- 0.31, and 1.28 +/- 0.08, respectively. CONCLUSIONS: SSH is a
      useful technique to detect differential expression genes and an effective method
      to clone novel genes. It provides a new method to investigate the molecular basis
      of the development of endometrial receptivity.

PMID- 17537307
TI  - [Study of symptoms in terminally ill patients with ovarian carcinoma].
AB  - OBJECTIVE: To investigate symptom characteristics and their their prevalence in
      terminally ill patients with ovarian carcinoma. METHODS: A retrospective study
      was carried out based on clinical data of 98 terminally ill patients with ovarian
      carcinoma who died in our hospital during January 1995 to December 2004. Fifteen
      most common symptoms were analyzed with a focus on the followings: symptom
      incidence, survival time after symptom occurrence, regularity of symptom cluster,
      and common causes of death. Fifteen symptoms were: pain, cachexia, pleural
      effusion and ascites, dyspnea, fever, intestinal obstruction, renal failure, bone
      marrow depression, lung infection, hemorrhage, deep venous thrombosis (DVT),
      intestinal or pancreatic fistula, mycotic infection, jaundice and emergency
      conditions. RESULTS: (1) The most prevalent symptom was pleural effusion and
      ascites (63%), followed by pain (60%), cachexia (59%), dyspnea (52%) and
      intestinal obstruction (49%). (2) The symptom which lasted longest survival time
      was mycotic infection (77 days), followed by intestinal or pancreatic fistula (75
      days), intestinal obstruction (67 days), pain (60 days) and cachexia (60 days).
      Symptoms such as bone marrow depression, renal failure, dyspnea and emergency
      conditions were comparatively critical associated with shorter survival times
      (14, 13, 12, 7 days, respectively). (3) Terminal symptoms occurred typically in
      clusters, with 4.9 +/- 1.5 symptoms per case. Of 98 cases, 84 cases (86%) had 4
      or more symptoms, with the median survival time of 63 days from the last day of
      anti-cancer therapy, and a slow death process. The remaining 14 cases (14%) with
      3 or fewer symptoms survived only 25 days, of which 10 cases (71%) died of
      emergency diseases. The survival time for two groups was significantly different
      (P<0.01). (4) The first four causes of death were as follows: intestinal
      obstruction (30%), infection (15%), emergencies (12%) and treatment complications
      (5%). CONCLUSION: Symptom characteristics and regularity are seen in terminally
      ill patients with ovarian carcinoma, the understanding of which is helpful for
      the improvement of symptom management and patients' quality of life.

PMID- 17537308
TI  - [Expression of phosphatidylinositol-3 kinase in epithelial ovarian carcinoma].
AB  - OBJECTIVE: To explore the expression and significance of phosphatidylinositol-3
      kinase (PI3K) in ovarian cancer, and the effect of combined PI3K inhibitor
      (LY294002) therapy with cisplatin on epithelial ovarian carcinoma, and to explore
      if there is a synergistic effect between the two therapies. METHODS: The
      expression levels of PI3K p85 subunit proteins and mRNA were evaluated by western
      blot and RT-PCR in normal ovarian tissue (G1), ovarian benign tumor tissue (G2),
      ovarian borderline tumor tissue (G3) and ovarian cancer tissue (G4), and the
      relevant clinical pathological parameters were analyzed. SKOV3 cells were
      isolated and cultured by enzymolysis method. SKOV3 cells were treated with
      culture medium only, LY294002 (1, 10, 30, 50, 100 micromol/L), cisplatin (0.33,
      1.25, 2.5, 5, 10 micromol/L), LY294002 (50 micromol/L) + cisplatin (10
      micromol/L) for 2 days, respectively. The effect of LY294002 and cisplatin on the
      growth of SKOV3 cells was measured by methyl thiazolyl tetrazolium assay.
      RESULTS: There was no positive expression of PI3K p85 subunit proteins in G1 and
      G2, while the expression was 2/6 in G3, and 85% (33/39) in G4. PI3K p85 subunit
      mRNA expression levels were 0.178 +/- 0.102 in G1, 0.643 +/- 0.112 in G2, 0.847
      +/- 0.058 in G3, 1.689 +/- 0.423 in G4; there was a significant difference
      between G1, G2, G3 and G4 (P<0.01). There was no significant correlation between
      protein expression and age at surgery or clinico-pathological staging (P>0.05).
      Significant differences were noted between protein expression levels in G4 (III,
      IV) and G4 (I, II; P<0.05). There was a significant difference between expression
      levels in tissues of different differentiation degrees (P<0.05). LY294002 and
      cisplatin inhibited the growth of SKOV3 cell in a concentration-dependent manner.
      The inhibitory activity of LY294002 at the concentration of 50 micromol/L was
      (46.0 +/- 2.0)% after treatment for two days. The inhibitory activity of
      cisplatin at the concentration of 10 micromol/L was (44.4 +/- 3.2)% after
      treatment for two days. After treatment for two days, the inhibitory activity of
      LY294002 50 micromol/L + cisplatin 10 micromol/L was (57.1 +/- 4.1)%. The
      inhibition effect on SKOV3 cell growth of the combined treatment group was better
      than the LY294002 or cisplatin treated group (P<0.01). CONCLUSIONS: PI3K p85
      subunit is highly expressed and positively correlated with ovarian cancer.
      Different expression levels exist in tissues of late ovarian cancer, earlier
      ovarian cancer, borderline tumor, benign ovarian tumor and normal ovarian tissue.
      The changes in PI3K p85 subunit are correlated with tumor differentiation degree,
      but not pathologic typing. LY294002 combined with cisplatin can significantly
      enhance the killing efficiency in ovarian cancer cells.

PMID- 17537309
TI  - [Relationship between the expression of P-glycoprotein, glutathione S-transferase
      pi and thymidylate synthase proteins and adenosine triphosphate tumor
      chemosensitivity assay in cervical cancer].
AB  - OBJECTIVE: To explore the feasibility of the adenosine triphosphate-tumor
      chemosensitivity assay (ATP-TCA) in human cervical cancer chemosensitivity
      testing and to analyze the relationship between the three drug resistance
      associated proteins: P-glycoprotein (P-gp); glutathione S-transferase-pi (GST
      pi); thymidylate synthase (TS) and ATP-TCA. METHODS: ATP-TCA was used to detect
      the sensitivity of 35 specimens of fresh cervical cancer to six cytotoxic drugs
      as follows: paclitaxel (TAX), cisplatin (DDP), bleomycin (BLM), gemcitabine
      (GEM), 5-fluorouracil (5-FU), irinotecan (CPT-11). Consecutive sections from 35
      cases of cervical cancer were assessed immunohistochemically for expression of P
      gp, GST-pi and TS proteins. RESULTS: (1) Thirty-two of 35 assays were completed
      successfully, with an evaluability rate of ATP-TCA at 91% (32/35). There was a
      marked heterogeneity of chemosensitivity in cervical cancer. The ex vivo
      sensitive rate of TAX was 88% (28/32), of 5-FU 72% (23/32), of GEM 62% (20/32),
      of DDP 19% (6/32), of BLM 16% (5/32), and of CPT-11 12% (4/32). (2) The
      expression of GST-pi and TS protein in cervical cancer was 66% (21/32) and 44%
      (14/32), which was associated with the resistance to DDP and 5-FU ex vivo
      (P=0.011, P=0.022), respectively; but the expression of P-gp protein was not
      associated with any resistance to TAX, 5-FU, GEM, DDP, BLM or CPT-11 ex vivo
      (P>0.05). CONCLUSIONS: ATP-TCA could be used to individualize chemotherapy by
      selecting agents for particular patients of cervical cancer. The expression of
      GST-pi and TS protein might be useful biomarkers to predict the resistance to DDP
      and 5-FU in patients with cervical cancer.

PMID- 17537315
TI  - [The appropriate treatment of spinal cord injury].

PMID- 17537316
TI  - [Profound insight for hyperextension spinal cord injury].

PMID- 17537317
TI  - [Several aspects of the diagnosis and treatment of atlanto-axial trauma].

PMID- 17537318
TI  - [Clinical characteristics and results of cervical spinal cord injury in the
      patients with ossification of the posterior longitudinal ligament].
AB  - OBJECTIVE: To investigate the clinical characteristics and results of cervical
      spinal cord injury (SCI) in the patients with ossification of the posterior
      longitudinal ligament (OPLL). METHODS: Nineteen patients with cervical SCI
      associated with OPLL were retrospectively analyzed. Data collection included: pre
      and postoperative neurological function, OPLL-type, MRI signal changes and
      surgical approaches. RESULTS: Spinal cord associated with OPLL was injured
      severely by mild trauma. Methylprednisolone sodium succinate was used within 8 h
      after trauma in 12 cases. Two of them died of complications. The neurological
      functions were markedly improved in the other 10 cases. Seventeen cases had
      surgical treatment. The neurological functions (Frankel grade) were improved
      significantly in the operated patients except for one, who died 27 d after
      operation. CONCLUSIONS: The patients with OPLL are prone to have severe SCI,
      which directly associates with the preexisting OPLL-type and hyper-intensity
      signal change in the spinal cord on MRI. Both of using methylprednisolone sodium
      succinate administration within 8 h after trauma and surgical decompression may
      improve the neurological outcomes.

PMID- 17537319
TI  - [Combined anterior and posterior approach for cervical fracture-dislocation with
      ankylosing spondylitis].
AB  - OBJECTIVE: To discuss the pathological characteristics of cervical spinal
      fracture of ankylosing spondylitis (AS), and surgical effect by combined anterior
      and posterior operation. METHODS: Eighteen AS patients with traumatic cervical
      fracture-dislocation were treated from January 2000 to January 2006. The symptom
      duration of AS was 14.5 years in average. Three cases had undergone osteotomy in
      lumbar spine. There were 4 cases of Grade A, 3 cases of Grade B, 9 cases of Grade
      C and 2 cases of Grade D in Frankel's score. All patients underwent surgical
      procedures by combined anterior and posterior approach. RESULTS: There were 4
      anterior-posterior procedures, 8 anterior-posterior-anterior procedures and 6
      posterior-anterior procedures. Seven patients had one stage operation and 11
      cases underwent two stage. There were some extent neurological improvement in 14
      incompletely paraplegic patients, no improvement in 4 complete paraplegia
      patients. The follow-up period was 21.2 months in average and the bone fusion was
      3.6 months. There were 4 complications during perioperative period and 1 in long
      term follow-up. CONCLUSIONS: The study suggests that anterior combined with
      posterior approach makes the spine stable and relieves the pressure immediately.
      It is the reasonable surgical strategy in the treatment of cervical spinal
      fracture-dislocation with AS.

PMID- 17537320
TI  - [Appraise operative outcome for acute central cervical spinal cord injuries
      without fracture and dislocation].
AB  - OBJECTIVE: To evaluate the surgical outcome for acute central cervical spinal
      cord injuries without fracture and dislocation. METHODS: A retrospective study
      was performed on 52 patients with acute central cervical cord injuries without
      fracture and dislocation from 2000 to 2005. All of patients underwent cervical
      anterior or posterior decompression, fusion and inter fixation. Spinal function
      was evaluated by ASIA (American Spinal Injury Association) guidelines. Pre- and
      post-operation ASIA scores were analyzed using liner correlation and regression.
      The neurological function was recorded during followed-up. The average follow-up
      was 29 months (range, 12 to 42). RESULTS: After operation, the ASIA scores
      increased significantly (P<0.01). Finally, ASIA motor, pin pricking and light
      touching scores of the 41 patients were 91 +/- 7, 107 +/- 6 and 107 +/- 6
      respectively. CONCLUSION: Decompression and inter fixation for injured segment
      can make a stable and broad space for spinal cord, promoting early neurological
      recovery and long-term improvement.

PMID- 17537321
TI  - [Surgical strategy for severe cervical spine dislocations].
AB  - OBJECTIVE: To evaluate the rate of open reduction and surgical strategy of severe
      cervical dislocation. METHODS: From March 2001 to March 2006, the data of 92
      cases of cervical dislocation over 1/2 were retrospectively studied. Garden Well
      traction with 1 - 3 kg weight were performed before operation. The patients were
      performed with diskectomy and reduction with anterior approach initially, for
      those that can not be reduced, corpectomy were performed and reduction procedures
      were repeated. The posterior reduction and fixation were followed when reduction
      can not be reached with anterior approach only. The succeed rate of reduction,
      rate of tracheotomy were recorded and fusion rate, Frankel score and visual
      analog scale (VAS) were evaluated. RESULTS: Reduction succeed in 38 cases after
      diskectomy, 44 after corpectomy and 7 after combined anterior-posterior-anterior
      procedure. Three cases got incompleteness reduction. Tracheotomy was done in 29
      cases. The Frankel score increased 0.5 degree and VAS was 2 averagely at the last
      follow-up. CONCLUSIONS: The succeed rate of anterior open reduction was 89.2%,
      and only 10.8% patients needs an additional combined posterior and anterior
      approach. For patients with completed spinal cord injury with dislocation above
      C(4), or with dislocation below C(5) but the edema on MRI T2 image are above C(4)
      level need tracheotomy. The operation be done until respiratory function stable.
      For patients with completed spinal cord injury with dislocation below C(4) and
      uncompleted spinal cord injury with dislocation above C(4), the rate of
      tracheotomy is relatively lower and early operation is recommended.

PMID- 17537322
TI  - [Percutaneous microendoscopic anterior release, fixation and fusion for
      irreducible atlanto-axial dislocation].
AB  - OBJECTIVE: To evaluate the safety and efficacy of one-stage percutaneous
      microendoscopic anterior release, trans-articular fixation and fusion to reduce
      and stabilize for irreducible atlanto-axial dislocation. METHODS: Eight
      consecutive patients were treated by percutaneous microendoscopic anterior
      release, trans-articular C(1-2) fixation and bone graft fusion. The mean age was
      33 years (range, 28-52 years). The pathology included odontoid dysplasia in 3
      patients, chronic odontoid fractures in 2, odontoid absence in 1, fasilar
      impression in 1 and malunion of odontoid fracture in 1. The classification of
      disability was that proposed by Symon and Lavender. There were moderate
      disability in 4, severe non-bedbound in 3, and severe bedridden in 1. RESULTS:
      The new technique was performed successfully in all cases. All patients underwent
      trans-articular C(1-2) screw fixation and anterior bone graft fusion. The average
      operation time was 120 min (90-150 min), and the average estimated blood loss was
      150 ml (100-250 ml). Seven cases resulted in anatomic reduction, 1 had partial
      reduction. The follow-up period was 8-16 months. The effective rate was 100%, and
      the excellent rate was 51.25%; the average improvement rate for the spinal canal
      decompression was 76.5%. There was no instrument failure or pseudarthrosis, and
      solid fusion was achieved in the all cases. The loss of axial rotation of
      cervical spine was 30-40 degrees . CONCLUSION: Percutaneous microendoscopic
      anterior release, fixation and fusion is an effective, reliable, and safe
      procedure for the treatment of irreducible atlanto-axial dislocation.

PMID- 17537323
TI  - [Change of motor evoked potential of the diaphragm after graded upper cervical
      spinal cord injury in rats].
AB  - OBJECTIVE: To study the change of motor evoked potential of the diaphragm after
      graded upper cervical cord injuries and analyze the prognosis of the respiratory
      function after upper cervical cord injuries by MEP. METHODS: The C(3, 4) spinal
      cord of 40 SD rats were injured with modified Allen method by weight drop force
      of 30 gcf, 50 gcf, 80 gcf, 100 gcf. The change of latent and amplitude of MEP of
      the diaphragm was observed before and after the spinal cord injuries (followed up
      for 1 month). At the same time, the femoral arterial blood of 0.2 ml was drawn.
      The pH value, the partial pressure of oxygen, the partial pressure of carbon
      dioxide, and the saturation of the blood oxygen were monitored. The change of the
      respiratory function was evaluated in the rats after cervical cord injuries. The
      relationship between the recovery of the respiratory function and the latent or
      amplitude was analyzed. RESULTS: The MEP wave of the diaphragm was stable before
      the upper cervical spinal cord injury in the rats. It was usually composed of a
      positive and negative wave. The latent period and peak-peak amplitude of wave
      were (3.13 +/- 0.29) ms and (6.78 +/- 3.48) mv. The latent period of the
      diaphragms MEP in rats change with graded upper cervical cord injuries
      significantly, the more sever the injury, the longer the latent period. There
      were obvious relationship between the change of the latent period and the
      recovery of the respiratory function. When the latent period prolonged 101%, the
      respiratory function is hardly to recovery. CONCLUSIONS: MEP can objectively and
      sensitively reflect the injury extent of the respiratory function when upper
      cervical cord is injured. It would be a reliable index to evaluate the long-term
      prognosis of respiratory function.

PMID- 17537327
TI  - [Analysis of the risk factors of upper urinary tract dilatation due to spinal
      cord injury].
AB  - OBJECTIVE: To evaluate the urodynamic risk factors of upper urinary tract
      dilatation (UUTD) secondary to spinal cord injury (SCI). METHODS: Ninety-six SCI
      patients of Tangshan earthquake were divided into 2 groups by ultrasonography: 16
      SCI patients (group A) with UUTD and 80 SCI patients (group B) without UUTD
      received urodynamic test. Responses were evaluated using single and multiple
      analysis after examination. RESULTS: The incidence of male was significantly
      higher than that of female. Residual urine volume, maximum cystometric capacity,
      detrusor leak point pressure and the incidence of bladder low compliance in group
      A were significantly higher than those in group B. There were no significant
      differences in age, the incidence of detrusor hyperreflexia, relative safe
      bladder capacity, the incidence of detrusor-sphincter dyssynergia, maximum flow
      rate and maximum urethral closure pressure between 2 groups. Bladder low
      compliance was cardinal risk factors according to Logistic regression analysis.
      CONCLUSION: An early urodynamic examination and treatment for SCI patients are
      important to prevent from bladder low compliance and upper urinary tract damage.

PMID- 17537328
TI  - [Total knee arthroplasty for extension ankylosing deformity].
AB  - OBJECTIVE: To discuss the outcomes and complications of total knee arthroplasty
      (TKA) for extension ankylosing deformity of the knee. METHODS: From January 1996
      to June 2006, total knee arthroplasty was performed on 8 patients (9 knees) with
      extension ankylosing deformity. The preoperative ROM of all patients was 0
      degrees . Preoperative knee and function score of KSS were 44 points (from 10 to
      68) and 17 points (from -10 to 55) respectively. RESULTS: The complications of
      all TKAs included patellar tendon avulsion in 1 knee, partial fracture of
      inferior patella in 1 knee, hematoma in 1, superficial infection in 1. All
      patients were followed up for an average of 40.4 months (from 7.0 to 120.0). The
      average postoperative ROM was 89 degrees (from 50 degrees to 120 degrees ).
      Postoperative knee and function score of KSS were 81 points (from 55 to 93) and
      79 points (from 50 to 90) respectively. Extension lag occurred in 2 knees, one
      was 10 degrees and the other was 25 degrees . One knee had undergone re-revision
      of changing the thicker tibial spacer for the reason of instability of joint 1
      year after revision. CONCLUSIONS: TKA performed in extension ankylosing deformity
      can get less satisfactory clinical results comparing with fixed flexion
      deformity. Exposure of the knee joint and separation of the fused bones,
      providing a mobile joint space plays crucial procedure for the next step of
      surgery. Preservation of sufficient bone stock of patella, protection of patellar
      tendon and blood supply of the knee and proper soft tissue balance are the key to
      TKA for extension ankylosing deformity.

PMID- 17537329
TI  - [Qualitative diagnosis and therapeutic strategy of atlanto-axial tuberculosis].
AB  - OBJECTIVE: To investigate the qualitative diagnosis method of atlanto-axial
      tuberculosis and the corresponding therapeutic strategy. METHODS: Twenty-two
      cases with atlanto-axial tuberculosis proven by histopathologic diagnosis were
      observed. Three cases and 17 cases underwent trans-oral biopsy and CT-guide
      percutaneous biopsy respectively, 2 cases were conformed by frozen section in
      operation. Thirteen of the 22 cases underwent surgical therapy: 1 case with
      anterior trans-oral radical eradication and fusion under Halo-vest
      immobilization, 7 cases with anterior cervical radical eradication, 1 case with
      anterior interbody fusion and titanic plate fixation, 2 cases were with posterior
      atlantoaxial interlaminar fusion and 2 cases with posterior cervical occipito
      axial titanic plate internal fixation and fusion. Other 9 cases accepted
      nonsurgical therapy: 8 cases with Halo-vest immobilization and 1 case with head
      halter traction. All cases were given appropriate antituberculotic chemotherapy
      for 12-18 months. RESULTS: All of the 22 cases were followed up, and the average
      time was 37 month. The lesion focus showed reparation and fusion in X-ray, and
      the results were satisfactory. CONCLUSIONS: Biopsy can acquire the qualitative
      diagnosis on atlanto-axial tuberculosis. The choice of therapy is made on the
      situation of cold abscess, pathological fracture, atlanto-axial dislocation and
      spinal cord compression.

PMID- 17537330
TI  - [Serum osteoprotegerin as a novel marker of bone metastasis in prostate cancer].
AB  - OBJECTIVE: To evaluate the diagnostic usefulness of serum osteoprotegerin (OPG)
      in prostate cancer bone metastasis. METHODS: Serum osteoprotegerin were measured
      by ELISA assay in 30 healthy men, 30 patients with benign prostatic hyperplasia,
      66 patients with prostate cancer including 36 without bone metastasis (30 with
      localized cancer, 6 with lymph node metastasis) and 30 with bone metastasis. The
      results associated with clinical data were calculated statistically. RESULTS:
      Serum osteoprotegerin were significantly increased in patients with bone
      metastasis compared with others (P<0.001). OPG level had a positive correlation
      with either prostate specific antigen (PSA) or Alkaline phosphatase (ALP) level
      (r=0.427, 0.277; P<0.001); and a positive correlation with either Gleason score
      or grade (r=0.427, 0.277; P<0.001). ROC analysis proved that OPG had better
      diagnostic accuracy than ALP for detecting bone metastasis in prostate cancer.
      CONCLUSION: Serum osteoprotegerin could be used as a marker for diagnosis of bone
      metastasis in prostate cancer.

PMID- 17537331
TI  - [Combined endocardial and epicardial radiofrequency modified Maze procedure in
      the treatment of atrial fibrillation].
AB  - OBJECTIVE: To evaluate the effectiveness of the combined endocardial and
      epicardial saline-irrigated radiofrequency modified maze procedure for the
      treatment of atrial fibrillation (AF). METHODS: During a period of 3 years, 295
      patients with AF having concomitant cardiac surgery underwent the procedure.
      Patients underwent either the endocardial and epicardial group (n=185) or the
      endocardial group (n=110) radiofrequency ablation. There were 124 males, 171
      females with a mean age of (52 +/- 11) year old. Mean duration of preoperative AF
      was 36 +/- 43 months. And about 90.8 percent valve pathology was rheumatic. Valve
      operation was performed in 289 patients, coronary artery bypass graft surgery in
      19 patients and congenital heart disease operation in 6 patients respectively.
      Follow-up for the whole patients ranged from 3 to 47 months (mean 28 +/- 5
      months). RESULTS: Ten patients died postoperatively (3.4%). Four patients died of
      low cardiac output, five patients died of multisystem and organ failure, one
      patient died of cerebral hernia. There were 2 patients died of nerves system
      complication during follow-up. At the end of the procedure 228 patients (77.3%)
      were sinus rhythm, including 78 patients (70.9%) in endocardial group while 150
      patients (81.1%) in endocardial and epicardial group (P<0.05). At late follow-up,
      191 of 259 patients (73.7%) were in stable sinus rhythm. Sinus rhythm was present
      in 64 patients (66.0%) in endocardial group while 127 patients (78.4%) in
      endocardial and epicardial group (P<0.05). Histopathology of the endocardial
      group revealed foci coagulative necrosis was limited to the endocardial side.
      While endocardial and epicardial ablation had full-thickness alteration of atrial
      tissue besides ill defined borders and inflammatory cell infiltration.
      CONCLUSIONS: Combined endocardial and epicardial saline-irrigated radiofrequency
      modified maze procedure was performed safely and efficiently. And it restored
      sinus rhythm better than endocardial ablation only.

PMID- 17537332
TI  - [Impact of different brain protection techniques upon postoperative temporary
      neurological dysfunction in aortic surgery with the aid of deep hypothermic
      circulatory arrest].
AB  - OBJECTIVE: To assess impact of different brain protection techniques upon
      postoperative temporary neurological dysfunction in aortic surgery with the aid
      of deep hypothermic circulatory arrest. METHODS: From January 2003 to December
      2005, 78 patients who met the inclusion criteria entered the present cohort, 43
      of whom were under the aid of deep hypothermic circulatory arrest plus retrograde
      cerebral perfusion (RCP group) and the other 35 under deep hypothermic
      circulatory arrest plus selective antegrade cerebral perfusion (SCP group). The
      present and grades of postoperative temporary neurological dysfunction were
      assessed by independent observers with the same criterion. The impact of duration
      of deep hypothermic circulatory arrest upon the postoperative temporary
      neurological dysfunction was also evaluated. RESULTS: The incidence of
      postoperative temporary neurological dysfunction was significantly higher in the
      RCP group than in the SCP group (15, 34.9% vs. 4, 11.4%, P<0.05). And long
      duration of deep hypothermic circulatory arrest (more than 50 min) has a negative
      impact on the postoperative temporary neurological dysfunction rate. CONCLUSIONS:
      Applying selective antegrade cerebral perfusion as the brain protection technique
      and shortening the duration of deep hypothermic circulatory arrest can reduce the
      incidence of temporary neurological dysfunction and preserve cerebral function
      more effectively.

PMID- 17537341
TI  - The clinical effectiveness and cost-effectiveness of treatments for children with
      idiopathic steroid-resistant nephrotic syndrome: a systematic review.
AB  - OBJECTIVES: To assess the clinical effectiveness and cost-effectiveness of
      treatments for children with idiopathic steroid-resistant nephrotic syndrome
      (SRNS). DATA SOURCES: Electronic databases from inception to February 2006,
      bibliographies of studies, and experts in the field. REVIEW METHODS: Studies were
      selected, quality assessed and data were extracted using recognised methods
      agreed a priori. Meta-analysis was undertaken where appropriate using the random
      effects model. Where data allowed, subgroup analysis was undertaken according to
      renal histopathology. RESULTS: Two systematic reviews and 11 trials were included
      in the clinical effectiveness review; however, the quality of reporting and
      methodology of the included studies was generally poor. No economic evaluations
      were identified. No statistically significant difference in remission rates was
      found between cyclophosphamide plus prednisone and prednisone alone for all
      children or those with focal segmental glomerulosclerosis (FSGS), also the time
      to response was statistically significantly less with cyclophosphamide (38.4 days
      versus 95.5 days). Remission rates were not statistically significantly different
      between intravenous and oral cyclophosphamide. Vomiting was common with
      intravenous cyclophosphamide, while pneumonia and alopecia occurred in the oral
      group. Ciclosporin statistically significantly increased the number of children
      with complete remission compared with placebo or supportive treatment, but not
      for the FSGS subgroup, adverse effects including infection and hypertension
      differed little between groups. No differences were found between azathioprine
      and placebo, with about 13% of each group having remission. Complete or partial
      remission occurred in six out of seven patients on the 18-month
      methylprednisolone regimen and three out of five patients on the 6-month regimen,
      for both groups renal function improved and adverse events such as hypertension
      and frequent infections occurred. Intravenous dexamethasone and
      methylprednisolone produced similar complete remission rates, partial remission
      rates, median time to response (about 10 days) and total number of adverse
      events, with hypertension as the most common. Six-hour urinary albumin and
      urinary albumin to creatinine ratio decreased statistically significantly with
      high-dose but not low-dose enalapril. Tuna fish oil was not associated with any
      statistically significant improvements in proteinuria, creatinine clearance,
      serum creatinine or lipid profiles compared with placebo. A very limited
      literature was found on costs associated with SRNS in children. The
      pharmaceutical cost of treatment varied considerably: an 8-week course of
      cyclophosphamide cost less than 6 pounds, while a course of ciclosporin cost
      almost 900 pounds per year. Treatment with tacrolimus, an alternative to
      ciclosporin, was estimated to cost in excess of 3400 pounds per year. Healthcare
      medical management costs were estimated; varying by treatment strategy, they
      ranged from 250 pounds to 930 pounds per year in patients not experiencing
      complications. Other longer term costs may also be incurred. Lack of data meant
      that cost-effectiveness modelling was not feasible. CONCLUSIONS: The clinical
      effectiveness literature on treatments for idiopathic SRNS in children is very
      limited. The available evidence suggests a beneficial effect of ciclosporin on
      remission rates and of cyclophosphamide on time to remission; however, the
      strength of the conclusions drawn is limited by the poor quality of the included
      studies. The other treatments included in this review were each evaluated by only
      one study, and none found a statistically significant effect. There is
      insufficient evidence to determine whether or not there is a clinically
      significant difference. The available data on costs and outcomes are sparse and
      do not permit the reliable modelling of the cost-effectiveness of treatments for
      SRNS at present. A modelling framework is suggested, should more relevant data
      become available. A well-designed adequately powered randomised controlled trial
      comparing ciclosporin with other treatments in children with SRNS without genetic
      mutation is required.

PMID- 17537342
TI  - Problem-based learning in public health workforce training: a discussion of
      educational principles and evidence.
AB  - Problem-based learning (PBL) has been implemented within numerous undergraduate
      health curricula but less so in workforce training. Public health practice
      requires many of the skills that PBL aims to develop such as teamwork, self
      directed learning and the integration of multiple sources of information within
      problem solving. This paper summarises the historical development of PBL and the
      educational principles underpinning it. It hypothesises that the public health
      workforce would benefit from some exposure to this type of learning and
      highlights some of the practical issues for its implementation.

PMID- 17537343
TI  - Using problem-based learning in public health service based training.
AB  - OBJECTIVES: This study explored the suitability and benefits of problem-based
      learning (PBL) in competency-based postgraduate public health training. The PBL
      was delivered within a rural retreat and included site visits. METHODS:
      Qualitative semistructured interviews with trainee public health officers and key
      informants. RESULTS: The learning approach (retreat-PBL combination with site
      visits) was valuable and relevant. Trainees reported a high learning impact with
      increased knowledge about the problems examined and rural public health practice.
      They also expressed an openness to work rurally. CONCLUSION: Collaboratively
      developed and delivered, experiential rural public health PBL provides a positive
      learning experience for trainees undertaking competency-based training in public
      health and could play an important workforce role. PBL appears to be suitable in
      rural and non-rural public health training settings.

PMID- 17537344
TI  - Use of communication technology among public health professionals in New South
      Wales, Australia.
AB  - We explored how six forms of communication technology (teleconferencing, web
      bulletin boards, web conferencing, videoconferencing, media streaming and
      satellite television) are currently being used in public health work in NSW.
      Twelve public health professionals working in the NSW health service were
      interviewed. Teleconferencing and videoconferencing were the most commonly used
      forms of communication technology. Factors that facilitated use included ease of
      access to facilities and assistance in organising and setting up the technique.
      Barriers to use included cost and the perception that the equipment was hard to
      set up and operate. Participants identified factors that assisted them to engage
      with these techniques.

PMID- 17537345
TI  - Influencing population health performance: introduction of standards for area
      health services in New South Wales.
AB  - Standards are a yardstick against which performance can be assessed and improved.
      Standards are well established in healthcare settings; however, population health
      standards have only recently been developed for area health services in NSW. This
      paper describes international and Australian population health standards, and
      presents the results of a pilot evaluation of the NSW Population Health Standards
      for Area Health Services against the Greater Western Area Health Service
      performance requirements. The findings revealed that the standards relating to
      the work of specialist population health staff feature in performance
      requirements; however the standards requiring the contribution of other health
      service staff do not. Population health standards have the potential to guide the
      health system towards population health goals.

PMID- 17537346
TI  - Health surveillance among a team of Australian health workers assisting tsunami
      victims in Aceh, Indonesia.
AB  - OBJECTIVE: To determine the extent and nature of health-related behaviours and
      outcomes among members of the first foreign medical team to arrive in Aceh,
      following the Boxing Day tsunami in 2004. METHODS: A cross sectional survey of
      team members 4 weeks after return from Aceh. RESULTS: Compliance with
      antimalarial chemoprophylaxis and insect repellent was high while in Aceh, but
      only one-third completed the course of chemoprophylaxis. The provision of
      prepackaged food and water was likely to have prevented enteric disease. Members
      reported mosquito bites, fatigue, sunburn, headache and anxiety about
      earthquakes. CONCLUSIONS: Provision of prepackaged food and water, preventive
      measures and information to members may be important in avoiding illness in such
      teams.

PMID- 17537347
TI  - [Local treatment of rectal cancer].

PMID- 17537348
TI  - [Comorbidity in children with epilepsy. I: Behaviour problems, ADHD and
      intelligence].
AB  - A search of the literature of studies on comorbidity in children with idiopathic
      and cryptogenic epilepsy revealed very few prospective longitudinal studies. The
      tendency was that children with epilepsy had a greater prevalence of comorbidity
      than healthy children, but more prospective longitudinal studies are needed to
      show the exact prevalence, grade and character. Behaviour problems seem to occur
      before the children have seizures, i.e. the behaviour problem seems to exist
      before the onset of epileptic seizures. There was no sound evidence for the
      prevalence of comorbidity in the form of ADHD. Children with epilepsy seem to
      have normal IQ.

PMID- 17537349
TI  - [Comorbidity in children with epilepsy. II: Aetiology].
AB  - A search of the literature of studies on comorbidity in children with idiopathic
      and cryptogenic epilepsy and its aetiology revealed few prospective longitudinal
      studies of evidence class II. There were too few studies on aetiology to
      determine the causes with certainty, but psychosocial factors seem vital, thus
      emphasizing the importance of information and support to the child and its
      family, including siblings. The cognitive and behavioural effect of antiepileptic
      medicine (other than phenobarbital) seems modest when AED is used
      monotherapeutically. Likewise, there only seems to be a modest connection between
      comorbidity and epilepsy-related variables such as age of onset, seizure types,
      EEG-changes and control of seizures.

PMID- 17537351
TI  - [Antibiotics for exacerbations of chronic obstructive pulmonary disease].

PMID- 17537350
TI  - [Effect of aromatase inhibitors on bone metabolism].
AB  - Aromatase inhibitors (AI) increase the disease-free survival of patients with
      receptor-positive breast cancer. They inhibit the endogenous production of
      estrogen by 50-90% and, in contrast to tamoxifen, reduce bone mineral density.
      Placebo-controlled studies have lacked statistical power to detect changes in
      fracture incidence; however, AI increases the incidence of fractures in
      comparison with tamoxifen. Therefore, we suggest that post-menopausal women
      starting on AI should be offered a DXA scan and that antiresorptive therapy
      should be considered for those with osteoporosis.

PMID- 17537352
TI  - [Therapeutic target for the use of erythropoietin (EPO): is subnormal better than
      normal?].

PMID- 17537353
TI  - [Transanal endoscopic microsurgery. The latest 5 years' experience in Roskilde
      County].
AB  - INTRODUCTION: Transanal endoscopic microsurgery (TEM) was developed by Gerhard
      Buess in 1983 as an alternative to traditional transanal surgery. The method has
      become more and more widespread in the treatment of benign as well as T1 rectum
      tumours. We have used the method for several years and we present our results in
      this paper. MATERIALS AND METHODS: Retrospective examination of patient files
      from consecutive registered patients who underwent TEM in the period June 1999 to
      November 2004, in all 76 operations on 74 patients. RESULTS: 49 patients had
      adenomas; both the recurrence and complication rate was 6%. Median follow-up
      period was 12 months (range 0-57). 15 had a T1 tumour removed; the recurrence
      rate was 15%. One had a serious complication. Median follow-up period was 12
      months (range 3-36). Eight had a T2 tumour removed; the recurrence rate was 16%.
      One had a serious complication. Median follow-up period was 21 months (range 9
      36). Two patients were treated for a T3 tumour as part of palliation. CONCLUSION:
      Our results are comparative to the largest foreign data. The recurrence rate is
      on the same level as open as well as laparoscopic surgery and far less than
      traditional transanal surgery. The complication risks are on the same level as
      laparoscopic access and far less than open surgery. However, preoperative
      investigation has to be developed further. Research is needed to clarify if
      selected patients with T2 cancer could be treated with TEM in combination with
      radiotherapy.

PMID- 17537354
TI  - [Injuries by colonoscopy and sigmoidoscopy requiring laparotomy. Claims to the
      Patient Insurance Corporation].
AB  - INTRODUCTION: Endoscopic colonic injury occurs in < 1% and may require surgical
      intervention. Mortality in Scandinavian studies is 0-0.06% after colonoscopy.
      MATERIALS AND METHODS: All claims to the Danish Patient Insurance Corporation
      from 1995-2005 were analysed. Indication, procedure, injury and course were
      registered. RESULTS: 111 had injury by colonoscopy and 11 by sigmoidoscopy in 46
      departments. 80% were ASA I-II. Indications were symptoms (63%), postoperative
      follow-up (7%), polyp (27%) or colitis surveillance (3%). 63% had polypectomy.
      Three had splenic injury and underwent splenectomy. The commonest site of
      perforation was the sigmoid (61%). The injury was diagnosed immediately in 28%,
      and after 24 hours (range 8-240) in the remainder. Treatment of perforations
      included suture with ileostomy (9%) or without ileostomy (29%), resection and
      anastomosis with enterostomy (12%) or without enterostomy (46%). Five had
      intraoperative splenic injury. 31% had complications, 15% required reoperation.
      One suffered a stroke, and one died after 17 days. Hospital stay was 29 days
      median (3-203). 42% required intensive care for 7 days (1-56). Complications were
      significantly less frequent in those diagnosed immediately. 37% of those with
      stoma declined restoration of continuity. During restoration 3/47 had splenic
      injury. Postoperatively one had anastomotic leak, one had wound dehiscence, and
      two died. CONCLUSION: Endoscopic colonic injury requiring laparotomy is serious
      and associated with a high rate of complications. Swift recognition and treatment
      may reduce the complication rate. Both primary and secondary surgical procedures
      should be handled by specialists.

PMID- 17537355
TI  - [A study of 355 consecutive acute poisoning cases admitted to an emergency ward
      at Copenhagen University Hospital, Bispebjerg in 2001].
AB  - INTRODUCTION: Epidemiology describing poisoned patients treated at Copenhagen
      University Hospital, Bispebjerg has not been published since 1993. We wanted to
      describe the pattern of intoxications. MATERIALS AND METHODS: A retrospective
      study of poisoned patients admitted to the emergency ward during 2001. A computer
      search of patients discharged with codes T36.0-T65.9 was supplemented by a hand
      search of the daily admittance lists. RESULTS: 355 patients with confirmed
      poisonings were found. 97% were poisoned by medications, alcohol (ethanol) or
      drugs of abuse. Only 3% were poisoned by other agents such as CO. 55% of
      poisonings were intentional, where paracetamol and benzodiazepines were the
      preferred agents. Sedative-hypnotics, alcohol, opioids, and drugs of abuse
      dominated the unintentional overdoses. Patients poisoned by paracetamol were
      younger and female, with an overrepresentation of young women of foreign origin.
      Activated charcoal was the preferred method of gastric decontamination. In 52% of
      the cases various discrepancies between discharge codes and actual poisonings
      were found. There were 5 deaths, 2 of which were from mixed overdoses with
      benzodiazepines involving the administration of flumazenil. The 355 cases
      represented 6% of all patients admitted to the department. CONCLUSION:
      Paracetamol, sedative-hypnotics and alcohol were the most common poisoning
      agents. Mortality was 1%. A general problem of discharge coding was found, which
      might implicate unreliability in statistics in this field.

PMID- 17537356
TI  - [An anthropological study of how young people and grown-ups with congenital heart
      disease understand their illness].
AB  - INTRODUCTION: An increasing number of grown-ups survive treatment for congenital
      heart disease due to improved prognostics for this group over the last decades.
      However, a smaller group of patients cannot be fully cured and encounter problems
      that require lifelong medical follow-up. This study examines how grown-ups with
      congenital heart disease (GUCH) understand their illness and body and describes
      the social and familial implications of the disease. MATERIALS AND METHODS: The
      study is based on participant observation in the GUCH patient organization,
      Hjerteungdom, and 11 semi-structured interviews with informants--all born with a
      severe congenital heart disease e.g. single ventricle, Steno Fallot, and
      transposition. RESULTS: The informants try to compensate for the lack of physical
      performance by adapting to alternative rolls during physical activity and
      pursuing academic interests in order to obtain social recognition. The informants
      wish to define themselves as competent and normal young adults in public life in
      order to avoid being treated as ill. At the same time the informants need to
      discuss health concerns openly, which they have traditionally done with their
      parents as they know their entire medical history. CONCLUSION: The informants
      experience limitations in their physical and social activities, but they try to
      adjust to living with a chronic disease and in this way they experience that the
      condition is controlled and mastered. GUCH patients can benefit from including
      personal and family issues in medical counselling because it can help them to
      cope with the disease in everyday life.

PMID- 17537357
TI  - [Septic superior ophthalmic vein thrombosis].
AB  - We report a case of septic right superior ophthalmic vein thrombosis in an 84
      year-old man with a suspected extracranial infection focus in the pharynx
      extending to the pterygoid fossa. The disease developed insidiously over a period
      of several weeks, and the diagnosis was confirmed by MR scanning. The literature
      on this uncommon cause of red, swollen eye is reviewed.

PMID- 17537358
TI  - [Terlipressin and reversible intestinal ischaemia].
AB  - The vasopressin analogue terlipressin (Glypressin) is generally considered an
      effective and safe treatment for acute oesophageal variceal haemorrhage. Safety
      is especially related to very few severe ischaemic side effects compared to those
      resulting from treatment with vasopressin. This case report describes reversible
      ischaemia in the colon and small intestine as seen by exploratory celiotomy in
      relation to treatment with terlipressin. The patient recovered fully without the
      need for intestinal resection.

PMID- 17537359
TI  - [Fast food promotes weight gain].
AB  - The total amounts of fat in a fast food menu consisting of French fries and fried
      Chicken Nuggets from McDonald's and KFC, respectively, bought in 35 different
      countries vary from 41 to 71 gram. In most countries the menu contained
      unacceptably high amounts of industrially-produced trans fat which contributes to
      an increased risk of ischaemic heart disease, weight gain, abdominal fat
      accumulation and type 2 diabetes. The quality of the ingredients in fast food
      ought to be better and the size of the portions smaller and less energy-dense so
      that frequent fast food meals do not increase the risk of obesity and diseases
      among customers.

PMID- 17537360
TI  - [Results of the SHOP LNHB98 (LMB89) trial in pediatric patients with B-cell non
      Hodgkin's lymphoma].
AB  - BACKGROUND AND OBJECTIVE: After the good results obtained by the Societe
      Francaise d'Oncologie Pediatrique (SFOP) regarding the pediatric B-type non
      Hodgkin's (Burkitt and large B-cell) lymphoma and L3 leukemia, the Sociedad
      Espanola de Hematologia y Oncologia Pediatricas (SHOP) decided to use the same
      treatment protocol. PATIENTS AND METHOD: Pediatric patients diagnosed with B-type
      non-Hodgkin's lymphoma without a previous history of malignant diseases were
      eligible for this study. They were classified in 3 groups of risk: group A
      (resected stage I and abdominal stage II), group B (not eligible for groups A or
      C), and group C (with central nervous system involvement and L3 leukemia). All
      received treatment according to the SFOP's LMB89 protocol. RESULTS: A total of
      153 patients were considered in this multicenter, prospective and non-randomized
      trial (1997-2005). The global and event-free survival (EFS) were found to be of
      88% (0.88; 95% confidence interval [CI], 0.83-0.93) and 85% (0.85; 95% CI, 0.79
      0.90), respectively. The EFS was 100% for the group A (n = 16), 86% (0.86; 95%
      CI, 0.79-0.92) for the group B (n = 113), and 68% (0.68; 95% CI, 0.49-0.86) for
      the group C (n = 24). CONCLUSIONS: The results confirm the good efficiency of the
      LMB89 protocol for treating B-cell lymphoma and L3 leukemia, despite having
      diminished the treatment intensity in the less risk groups. The worst prognostic
      factor was found to be a central nervous system involvement, whereas being
      younger than 10 years was confirmed to be a favorable prognostic factor. In
      addition, no differences were evidenced between Burkitt and large B-cell
      lymphoma.

PMID- 17537361
TI  - [Adequacy of the treatment of hypertensive patients with metabolic syndrome].
AB  - BACKGROUND AND OBJECTIVE: The aim of this study was to know the treatment of
      hypertensive patients with metabolic syndrome (MetS) attended in primary care
      setting, as well as the blood pressure and LDL-cholesterol (LDL-c) rates, and to
      compare these data with those of the hypertensive population without MetS.
      PATIENTS AND METHOD: We analyzed the subset of patients with MetS from those
      included in the PRESCOT study (a cross-sectional study of hypertensive subjects
      >18 years attended in primary care). The PRESCOT population was composed by
      12,954 patients (49.9% females; 62.1+/-10.7 years). MetS was diagnosed according
      to NCEP-ATP-III criteria. RESULTS: 6,736 (52%) patients fulfilled diagnosis
      criteria of MetS (mean age 62.3+/-10.5 years; 43.9% males). Almost all MetS
      patients (98.2%) were on any medication, and 80.5% were at least on two drugs.
      Despite hypertensive MetS patients were treated with more antihypertensive
      medications (45.3% vs 36.6% were on two or more drugs, p < 0.001) and used more
      lipid-lowering agents (43% vs 39.1%, p < 0.001) than patients without MetS, the
      blood pressure control (according to European guidelines) and LDL-c control
      (according to NCEP-ATP III) rates were lower in patients with MetS (17.2% vs
      33.6% and 17.2% vs 35.7%, p < 0.0001). Only 4.7% of patients with MetS were
      adequately controlled for both factors, LDL-c and blood pressure, vs 13.5% of
      patients without MetS, (p < 0.0001). CONCLUSIONS: The presence of MetS in the
      hypertensive population attended in Spanish primary care settings is very common.
      Even though in hypertensives with MetS more drugs are prescribed, blood pressure
      and LDL-c control rates are worse in this population than in patients without
      MetS.

PMID- 17537362
TI  - The influence of the age in the risk of the prothrombin G20210A mutation for
      spontaneous venous thrombosis.
AB  - BACKGROUND AND OBJECTIVE: Factor V Leiden mutation (FVL), and the prothrombin
      G20210A mutation (PT G20210A) are polymorphisms with a weak risk factor for
      venous thromboembolic disease. The probability of spontaneous venous thrombosis
      in carriers of thrombophilic mutations (FVL and PT G20210A) was analyzed.
      PATIENTS AND METHOD: We studied 735 individuals (407 were healthy controls and
      328 patients with venous thrombosis) with respect to FVL and PT G20210A,
      determined by polimerase chain reaction in liquid phase, real time. chi2 test and
      logistic regression analysis were used to evaluate the results. The dates were
      analyzed with the statistical program SPSS v. 14.0. RESULTS: The carrier patients
      of PT G20210A mutation whose age was over 40 years had a risk factor for
      spontaneous venous thrombosis which was 9.28 (odds ratio [OR]) (95% confidence
      interval [CI], 3.01-28.60; p < 0.0005) times greater than carriers of the PT
      G20210A mutation who were 40 year-old or younger. In our patients, being male
      meant a weak risk factor for venous spontaneous thrombosis (p = 0.021; OR = 1.64;
      95% CI, 1.08-2.51) . CONCLUSIONS: Our results demonstrate a potentiation of the
      thrombotic risk by an increase of age in the carriers of the PT G20210A mutation.

PMID- 17537363
TI  - [Genetic thrombophilia and cerebral venous thrombosis].
AB  - BACKGROUND AND OBJECTIVE: Sinus cerebral venous thrombosis (SCVT) is an
      unfrequent disease, with variable clinical presentation and prognosis. The
      objective of this study was to analyze the relationship between factor V Leiden,
      prothrombin G20210A mutation (PT 20210A) and MTHR and SCVT. PATIENTS AND METHOD:
      Cases and control study including 15 patients with diagnosis of SCVT. We
      performed a genetic analysis of the mutation of factor V Leiden, the PT G20210A
      and the C677T of the MTHR. RESULTS: Factor V Leiden: 26.6% heterozygote in cases
      and only 8.3% in control group, thus showing odds ratio [OR] = 4,0. Mutation
      20210A of the prothrombin: in patients, 13.3% of heterozygote, while a 6,6% in
      controls, finding an OR = 2.1 (95% confidence interval [CI], 1.67-10.04).
      Mutation of the MTHR: 40% heterozygote and 20% homozygote in patients group
      respect to 51.6% and 6,9%, respectively, in the control group, but no statistical
      differences were found. CONCLUSIONS: The presence of factor V Leiden and PT
      20210A are risk factors for SCVT, but not the mutation of the MTHR.

PMID- 17537364
TI  - [Hereditary thrombophilia: learnt lessons and pending duties].

PMID- 17537365
TI  - [Sulfamides historical facts disclosed through the news media: the case of The
      New York Times].

PMID- 17537366
TI  - [To whom should a study of thrombophilia be performed?].

PMID- 17537367
TI  - [Antibodies to citrullinated peptides in rheumathoid arthritis].
AB  - Rheumatoid arthritis is a systemic autoimmune disease characterized by chronic
      inflammation of the synovial joints leading to progressive joint destruction. The
      serum of these patients contains a large repertoire of autoantibodies, mainly
      rheumatoid factor, which is part of the ACR classification criteria in spite of
      having only moderate specificity. Antibodies directed to citrullinated proteins
      provide clinicians with a valuable tool for early diagnosis. It has been shown
      that these antibodies can be detected years before presentation of the first
      symptom and are very useful for diagnosis and prognosis, due to good sensitivity
      and specificity and prediction of development of erosive disease. The immune
      response against citrullinated antigens is characteristic of an immuno-genetic
      subtype of disease, in which the combined role of genes, environmental factors
      and autoimmunity has become the prime suspected for disease pathogenesis. A model
      is proposed of how these antibodies are produced and lead to chronic synovial
      inflammation.

PMID- 17537368
TI  - [Oral antiagregant drugs in peroperative period. To be maintained or to be
      removed?].

PMID- 17537369
TI  - [Bilateral spontaneous quadricipital tendon rupture in a kidney transplantation
      patient].

PMID- 17537370
TI  - [Subacute meningitis and persistent hypoglucorrachia. Its relationship with the
      onset of immune reconstitution inflammatory syndrome].

PMID- 17537371
TI  - [Heatstroke during topiramate treatment].

PMID- 17537372
TI  - [Congratulations, PubMed].

PMID- 17537373
TI  - [Non pharmacologic and alternative treatments in fibromyalgia].

PMID- 17537374
TI  - [Massive pneumoencephaly after meningococcal meningitis].

PMID- 17537376
TI  - Autoantibodies as predictors of disease: the clinical and experimental evidence.
AB  - Several studies have shown that autoimmune diseases are preceded by a long pre
      clinical phase, and that many autoantibodies can be detected in the serum of
      asymptomatic subjects years before the clinical manifestations become evident.
      Tests for these autoantibodies could therefore be used in principle in screening
      studies on unselected populations to identify individuals predisposed to the
      development of the disease at an early stage, and start treatment or adopt
      preventive measures where possible. This aspect has aroused particular interest,
      as multiplex investigation techniques are already available, and microarray
      methods are under development, which will probably allow tens or hundreds of
      autoantibodies to be measured simultaneously. However, as no antibody assay
      offers 100% specificity, and the results are strongly dependent on the assay
      method used to measure the autoantibodies, it is essential to use assay methods
      with high diagnostic specificity, to minimize false positives and obtain a high
      positive predictive value. This review examines the various autoantibodies for
      which a role in predicting the development of an autoimmune disease has been
      demonstrated in long-term prospective studies.

PMID- 17537377
TI  - Recent advances in diagnostic technologies and their impact in autoimmune
      diseases.
AB  - Conventional immunological methods for the detection of serum autoantibodies have
      been an essential tool for the diagnosis of autoimmune diseases for 40 years: in
      the last decade autoantibody tests have become accepted criteria for the
      diagnosis and classification of the main systemic and organ-specific autoimmune
      diseases. The high degree of purification reached by the autoantigens used in
      these methods has allowed high diagnostic sensitivity and specificity, especially
      in the case of some new autoantibodies of particular clinical significance, such
      as anti-nucleosome, anti-transglutaminase, anti-TSH receptor and anti
      citrullinated protein autoantibodies. In the last 5 years the advent of proteomic
      technology, which allows the simultaneous measurement of a number of
      autoantibodies (multiplexing), has opened up new horizons in the diagnosis of
      autoimmune diseases. Multiplexing is particularly interesting for clinical
      laboratories, for organisational, logistical/managerial, physiopathological and
      research reasons. The emerging technologies are represented by systems based on
      planar or non-planar (suspension) arrays: the latter include methods which use
      addressable microbeads or nanobarcoded particles. Within a few years, the new
      methods will allow testing of individual autoantibody profiles, which will
      probably improve understanding of the physiopathology of autoimmunity, allow
      early diagnosis (due to the predictive value of autoantibodies), and drive the
      diffusion of antigen-specific therapies in autoimmune diseases.

PMID- 17537378
TI  - Interpretative comments on autoantibody tests.
AB  - Immunology laboratories perform diagnostic tests to identify the autoantibody
      markers needed to classify disorders which are complex, often rare, and hard to
      define. The recent introduction of new markers and the use of increasingly
      complicated assay procedures can cause difficulty in interpreting test results.
      Moreover, during the performance of some tests, some autoantibodies which were
      not requested, and consequently not expected, may be identified by chance. It is
      advisable for these positive results to be reported only when they have a high
      predictive value and suggest the possible presence of an autoimmune disease. An
      interpretative comment on autoantibody test results is crucial in a number of
      cases: when autoantibodies with a significant clinical correlation (high
      specificity) are found; when two or more methods are used to determine the same
      autoantibody and the results disagree; when unexpected autoantibody positivity is
      found and in case of results generated by further diagnostic tests conducted by
      the laboratory on its own initiative. The interpretative comment should be based
      on the patient's personal characteristics (sex, age) and the other laboratory
      parameters available; it should specify the diagnostic accuracy of the assay
      methods used, the clinical and diagnostic correlations of the antibodies which
      tested positive, and any further tests needed to complete the diagnostic process.

PMID- 17537379
TI  - The management of the patient with unexpected autoantibody positivity.
AB  - Different autoantibodies are often measured simultaneously; this typically occurs
      when using indirect immunofluorescence on tissue sections or multiplex detection
      systems and may generate clinically "unexpected" positivities (i.e., without any
      relation to the disease under investigation). Their number is expected to
      increase with the development of microarray systems in autoantibody assays. In
      general, when examining patients with such unexpected findings, it is necessary
      to take into account that: a) autoantibody positivities are much more frequent
      than autoimmune diseases; b) the positive predictive value of an autoantibody
      positivity depends upon the diagnostic accuracy of the test and disease
      prevalence; c) autoantibodies may be risk factors for autoimmune disease or may
      also have a pathogenetic role by themselves. In this article we will highlight
      the possible problems raised by some relatively common situations, related to
      anti-nuclear, anti-thyroid, anti-phospholipid and anti-tissue transglutaminase
      autoantibodies. The need for specific strategies is outlined.

PMID- 17537380
TI  - Epidemiological and ethical aspects of multiplex autoantibody testing.
AB  - Arrays are one of the technologies able to detect autoantibodies by measuring
      simultaneously many thousands of markers from a unique biological sample. The
      main purpose of a diagnostic test is making an early and accurate diagnosis. From
      a statistical point of view, multiple testing increases the probability of false
      positive and false negative results. Some correction methods are available to
      account for this problem for instance family-wise error rate or false discovery
      rate. From an ethical point of view, the decision to accept or decline a test not
      requested has to be made autonomously. Some people may seek clarification about
      tests and implications of their choices. A scarcity of proven measures to reduce
      mortality has to be considered too. Reasons may also include avoidance of
      psychological harm or anxiety. Moreover, protection of confidentiality and
      privacy has to be respected. In conclusion, the fact that testing is optional and
      that surveillance advice can be offered on the basis of risk alone without a test
      should be discussed in the consultation. The implication of a positive test
      result should be discussed to make a decision about the degree to which early
      treatment of the condition is better than late (or no) treatment.

PMID- 17537381
TI  - The laboratory approach to the diagnosis of autoimmune diseases: is it time to
      change?
AB  - Array technology and proteomics are about to launch the era of multiplexed
      analysis, which allows simultaneous detection of numerous autoantibody
      specificities and the possibility of defining broad autoantibody profiles. This
      will probably improve disease staging, risk stratification, prognosis and
      treatment. However, although these technologies are very promising, they are
      still in their infancy, and therefore need to undergo strict analytical and
      clinical validation processes. The latter should involve clinicians and
      pathologists in prospective, multicentric studies conducted on large numbers of
      patients to define the specific significance of the various autoantibody
      profiles. Establishing common standards for the publication and sharing of
      microarray-generated data will be important for this purpose. Only when these
      studies have been completed will these new technologies find a place in clinical
      laboratories. Although we are entering a decade which will probably see a radical
      change in the diagnostic approach to autoimmune diseases, we do not yet have
      sufficient knowledge to apply proteomic technologies on a large scale. For the
      time being, therefore, it is advisable to continue using well-established
      approaches and diagnostic algorithms such as those reported in the international
      guidelines, which have been prepared in accordance with the principles of
      appropriateness and evidence-based medicine.

PMID- 17537382
TI  - Gender and autoimmunity.
AB  - The enhanced immunoreactivity in females is a double-edged sword that provides
      better protection against infections, but may lead to enhanced autoreactivity and
      thereby contribute to the induction of autoimmunity. Autoimmune diseases
      demonstrate a gender bias and represent the fifth leading cause of death by
      disease among females of reproductive age. Clinical and murine experimental
      studies indicate that the gender bias in autoimmunity may be influenced by sex
      hormones, predominantly displayed in the development and exacerbations of the
      prototypical autoimmune disease lupus. The associations between sex hormones and
      other autoimmune diseases are less clear. Our review on the impact of gender via
      sex hormones and sex related genes in the pathogenesis of several autoimmune
      diseases suggests that a better understanding of the underlying mechanisms behind
      the sexual dimorphism of the immune system may lead to the development of novel
      therapeutic approaches to autoimmunity.

PMID- 17537383
TI  - Therapeutic options in autoimmune myasthenia gravis.
AB  - Autoimmune myasthenia gravis (MG) is associated with circulating antibodies to
      AChR, modification of the synaptic cleft, and destruction of the postsynaptic
      neuromuscular membrane. The hallmark is fluctuating muscular weakness and
      fatigability of muscles on sustained repeated activity. Various drugs and
      invasive procedures have been used in the treatment of MG including
      acetylcholinesterase inhibitors, corticosteroids, azathioprine, cyclosporine,
      cyclophosphamide, mycophenolate mofetil, tacrolimus, etanercept, intravenous
      immunoglobulin, plasma exchange and thymectomy. We review the role of each of
      these drugs and invasive procedures in MG. Although current treatment is highly
      successful and mortality is almost nil, further trials are required to identify
      the most suitable treatments for different subgroups of MG patients. In addition,
      safer and more potent drugs are required as most current drugs have major side
      effects due to immunosuppression. Therefore, the goal of novel therapies should
      be increased specificity of the immune-directed agents.

PMID- 17537384
TI  - Cardiac manifestations in antiphospholipid syndrome.
AB  - Antiphospholipid syndrome (APS) is a systemic autoimmune disease associated with
      arterial and venous thrombotic events and recurrent fetal loss. Cardiac
      manifestations in APS primarily include accelerated atherosclerosis leading to
      cardiovascular disease. There is increased cardiovascular mortality in APS.
      Cardiovascular risk is even higher in secondary APS in lupus patients. Several
      traditional and disease-related, autoimmune-inflammatory risk factors are
      involved in APS-associated atherosclerosis and its clinical manifestations.
      Antiphospholipid antibodies (APA), lupus anticoagulant, anti-oxLDL and other
      antibodies have been implicated in vascular events underlying APS. The primary
      and secondary prevention of atherosclerosis and CAD in these diseases includes
      drug treatment, such as the use of statins and aspirin, as well as lifestyle
      modifications. Apart from atherosclerosis and CVD, other cardiac manifestations
      may also be present in these patients. Among these conditions, valvular disease
      including thickening and vegetations is the most common. APA are involved in the
      pathogenesis of Libman-Sacks endocarditis usually associated with SLE. In
      addition, ventricular dysfunction, intracardiac thrombi and myxomas, pulmonary
      hypertension may also exist in APS patients. Early diagnosis of APS, thorough
      examination of the heart, control of traditional risk factors by lifestyle
      modifications and pharmacotherapy, probably anti-inflammatory treatment, and
      close follow-up of APS patients may help to minimize cardiovascular risk in these
      individuals.

PMID- 17537386
TI  - Meta-analysis of HLA-DRB1 polymorphism in Latin American patients with rheumatoid
      arthritis.
AB  - OBJECTIVES: To estimate the common effect size of HLA-DRB1 alleles on rheumatoid
      arthritis (RA) susceptibility across Latin America populations through a meta
      analysis combining the results of published data. METHODS: Case-control studies
      on HLA-DRB1 association with RA in Latin America were searched up to October
      2006. Genotype frequencies were extracted according to both shared epitope (SE)
      and HLA-DR4 positive or negative alleles. The effect summary odds ratio (OR) and
      95% confidence intervals was obtained. Heterogeneity and publication bias were
      assessed. RESULTS: Eight studies containing 684 cases and 1015 controls were
      included. Under the random effects model, the common OR was 3.28 (1.93, 5.60)
      (p<0.0001) and 3.54 (2.47, 5.05) (p=4.22 x 10(-12)) for HLA-DR4 and SE,
      respectively. There was no evidence of publication bias according to Funnel plot
      and Egger's regression test (p=0,445 for DR4 and p=0,464 for SE meta-analysis).
      Significant heterogeneity was observed for HLA-DR4 (I2=81.06%, Q=36.96,
      p=0.000005) but not for the SE meta-analysis. CONCLUSIONS: HLA-DR4 and SE
      positive HLA-DRB1 alleles (mainly HLA-DRB10404) are associated with RA in Latin
      Americans. Heterogeneity is expected owing to the diverse degree of admixture
      between the examined populations. Our findings support the HLA as a major
      susceptibility locus for RA and validate the SE hypothesis in Latin America.

PMID- 17537387
TI  - Ocular manifestations in antiphospholipid syndrome.
AB  - Antiphospholipid syndrome (APS) is characterized by increased hypercoagulability
      and divergent symptoms including ocular manifestations. In APS patients arterial
      and/or venous thromboses and repeated fetal loss are diagnosed in presence of
      antiphospholipid (aPL) antibodies. Antiphospholipid antibodies are heterogeneous
      group of immunoglobulins with different antigenic structure. Primary APS is
      defined in the absence of underlying disease, while secondary APS is seen within
      another pathological condition. In both primary and secondary APS ocular and
      neuroophthalmic manifestations, such as retinal arteritis, retinal venous
      occlusion, ischemic optic neuropathy, transient loss of vision - amaurosis fugax,
      diplopia and others can be diagnosed. In secondary APS occlusion of central
      retinal artery and vein (OACR, OVCR) is the most common finding, thus when found
      in younger patients it should be considered indicative of APS. Bilateral ocular
      changes are considered more significant since they affect both ocular function
      and life prognosis.

PMID- 17537385
TI  - B cells in autoimmune diseases: insights from analyses of immunoglobulin variable
      (Ig V) gene usage.
AB  - The role of B cells in autoimmune diseases has not been fully elucidated. It is
      also unclear whether breaking of B cell tolerance in patients with autoimmune
      diseases is due to underlying defects in the molecular mechanisms involved in the
      arrangement of antibody genes or deficiencies in the subsequent selective
      influences that shape the antibody repertoire. Analysis of immunoglobulin (Ig)
      variable (V) gene usage is beginning to provide answers to some of these
      questions. Such analyses have identified some differences in the basic Ig V gene
      repertoire of patients with autoimmune diseases compared to healthy controls,
      even though none of these differences can be considered major. Defects in
      positive and negative selection, mutational targeting and, in some cases,
      receptor editing have also been detected. In addition, analysis of Ig V gene
      usage in target organs and tissues of patients with autoimmune diseases has
      clearly demonstrated that there is a highly compartmentalized clonal expansion of
      B cells driven by a limited number of antigens in these tissues. Great progress
      has been made in the structural and functional characterization of disease
      associated antibodies, largely because of the development of the combinatorial
      library technique. Use of antibodies generated by this technique offers great
      promise in identifying B cell epitopes on known target antigens and in gaining
      greater insights into the pathogenic role of B cells in both B and T cell
      mediated autoimmune diseases.

PMID- 17537388
TI  - Peripheral expression of RAG in human B lymphocytes in normal and pathological
      conditions is dependent on interleukin-6.
AB  - Establishment of the B cell repertoire is regulated by recombination activating
      genes RAG1 and RAG2 proteins in the bone marrow. Tolerance of autoreactivity is
      mainly prevented by receptor editing, i.e. synthesis of a new B cell receptor
      following re-expression of RAG1 and RAG2. Numerous signals can lead to RAG up
      regulation, all in association with soluble cytokines. In the periphery,
      autoreactive B cells or low-affinity B cell receptor synthesis may appear
      following antigenic immune response. Receptor revision, i.e. new immunoglobulin
      gene rearrangement can participate to the control of these lymphocytes following
      new RAG1 and RAG2 re-induction. Though signals leading to this peripheral RAG up
      regulation are poorly described, IL-6 seems to have a preponderant role.
      Therefore, the elevated levels of IL-6 secreted by activated B cells in systemic
      lupus erythematosus might contribute to the maintenance of abnormal RAG
      expression, and in turn may participate to the emergence of autoreactive B cells
      in the periphery.

PMID- 17537389
TI  - Psychiatric manifestations in systemic lupus erythematosus.
AB  - Psychiatric abnormalities are common in systemic lupus erythematosus (SLE) with a
      prevalence of 17% to 75%, reflecting different methods of patient selection and
      assessment, the different professional orientation of clinicians, and lack of an
      accepted consensus for diagnosing active neuropsychiatric lupus (NPSLE). The
      psychiatric syndromes included in the ACR Neuropsychiatric Lupus Nomenclature
      Committee criteria are cognitive dysfunction, acute confusional state (delirium),
      anxiety disorder, mood disorder, and psychosis. In SLE patients, identification
      of psychiatric phenomena and the generation of a differential diagnosis are
      crucial. Possible mechanisms include vascular injury and pathogenic antibodies.
      Treatment strategies are based on small case studies. The purpose of this review
      is to discuss clinical manifestations, pathogenesis and the present therapeutic
      options in psychiatric lupus.

PMID- 17537390
TI  - Identification of four members of the Anopheles funestus (Diptera: Culicidae)
      group and their role in Plasmodium falciparum transmission in Bagamoyo coastal
      Tanzania.
AB  - The role of Anopheles funestus group in malaria transmission was investigated in
      Bagamoyo coastal Tanzania, in the process of characterizing the area as a malaria
      vaccine testing site. Mosquitoes were sampled inside houses and multiplex PCR was
      used to identify 649 specimens. The following species were found: A. funestus
      s.s. (84.3%), A. leesoni (13.6%), A. rivulorum (1.5%) and A. parensis (0.6%).
      Multiplex PCR of 147 blood-fed specimens showed that over half (57.1%) of the
      identifiable blood meals were taken from human hosts, and human blood index in A.
      funestus and A. leesoni was 55% and 82% respectively. Plasmodium falciparum
      infection rate determined by nested PCR was 11% in A. funestus s.s. Although the
      abundance was low, 26 specimens of A. leesoni, two of A. rivolurum and one of A.
      parensis were found positive for P. falciparum. The presence of four A. funestus
      species in Tanzania emphasizes the relevance to define precisely their spatial
      and temporal distribution, specific behaviour, ecology and exact role in malaria
      transmission.

PMID- 17537391
TI  - Contact angle hysteresis on fluoropolymer surfaces.
AB  - Contact angle hysteresis of liquids with different molecular and geometrical
      properties on high quality films of four fluoropolymers was studied. A number of
      different causes are identified for hysteresis. With n-alkanes as probe liquids,
      contact angle hysteresis is found to be strongly related to the configuration of
      polymer chains. The largest hysteresis is obtained with amorphous polymers
      whereas the smallest hysteresis occurs for polymers with ordered molecular
      chains. This is explained in terms of sorption of liquid by the solid and
      penetration of liquid into the polymer film. Correlation of contact angle
      hysteresis with the size of n-alkane molecules supports this conclusion. On the
      films of two amorphous fluoropolymers with different molecular configurations,
      contact angle hysteresis of one and the same liquid with "bulky" molecules is
      shown to be quite different. On the surfaces of Teflon AF 1600, with stiff
      molecular chains, the receding angles of the probe liquids are independent of
      contact time between solid and liquid and similar hysteresis is obtained for all
      the liquids. Retention of liquid molecules on the solid surface is proposed as
      the most likely cause of hysteresis in these systems. On the other hand, with EGC
      1700 films that consist of flexible chains, the receding angles are strongly time
      dependent and the hysteresis is large. Contact angle hysteresis increases even
      further when liquids with strong dipolar intermolecular forces are used. In this
      case, major reorganization of EGC-1700 chains due to contact with the test
      liquids is suggested as the cause. The effect of rate of motion of the three
      phase line on the advancing and receding contact angles, and therefore contact
      angle hysteresis, is investigated. For low viscous liquids, contact angles are
      independent of the drop front velocity up to approximately 10 mm/min. This agrees
      with the results of an earlier study that showed that the rate-dependence of the
      contact angles is an issue only for liquids with high viscosity.

PMID- 17537392
TI  - Detection and characterization of N-alpha-chloramines by electrospray tandem mass
      spectrometry.
AB  - Hypochlorous acid (HOCl) is a major product of activated neutrophils and may be
      important in antimicrobial activities of cells by oxidation or chlorination of
      susceptible amino acids. Three major peaks separated using C18 reverse phase-high
      performance liquid chromatography RP-HPLC after incubation of leucine enkephalin
      (LeuEnk) with HOCl. Electrospray mass spectrometry showed masses of m/z 556.2,
      590.2, and 624.4 corresponding to unmodified LeuEnk and peptides altered by
      addition of one or two chlorines (Cl). Formation of stable N-alpha-chloramines
      was indicated because the chlorinated peptides were readily reduced with the
      physiological reductants glutathione and ascorbic acid to LeuEnk (m/z 556.2)
      within 10 min. Sequence-specific ions observed in product ion spectra of single
      charged monochlorinated and dichlorinated peptides were consistent with
      modification of the N-terminal amine. There was no evidence for chlorination of
      the Tyr aromatic ring in any spectra. Similar RP-HPLC profiles were obtained
      after oxidation of des-Tyr1-LeuEnk (GGFL) with the masses of the major products
      being m/z 393.3, 427.2, and 461.1. These were identified as unmodified GGFL, N
      alpha-Cl-GGFL, and N-alpha-Cl2-GGFL based on comparison of tandem mass spectra.
      Oxidation of Met and formation of disulfide dimers was observed after incubation
      of either N-alpha-Cl-LeuEnk or N-alpha-Cl2-LeuEnk with a protein, indicating that
      both peptide N-alpha-chloramines were able to readily modify sulfur-containing
      amino acids within proteins. These data indicate initial formation of stable N
      alpha-chorinated peptides after incubation with HOCl and suggest that N-alpha
      chlorinated peptides may exist for some hours in the absence of physiological
      reducing agents or sulfur-containing amino acids.

PMID- 17537393
TI  - Extending the capabilities of nature's most versatile catalysts: directed
      evolution of mammalian xenobiotic-metabolizing P450s.
AB  - Cytochrome P450 enzymes are amongst the most versatile enzymatic catalysts known.
      The ability to introduce a single atom of oxygen into an organic substrate has
      led to the diversification and exploitation of these enzymes throughout nature.
      Nowhere is this versatility more apparent than in the mammalian liver, where P450
      monooxygenases catalyze the metabolic clearance of innumerate drugs and other
      environmental chemicals. In addition to the aromatic and aliphatic
      hydroxylations, N- and O-dealkylations, and heteroatom oxidations that are common
      in drug metabolism, many more unusual reactions catalyzed by P450s have been
      discovered, including reductions, group transfers and other biotransformations
      not typically associated with monooxygenases. A research area that shows great
      potential for development over the next few decades is the directed evolution of
      P450s as biocatalysts. Mammalian xenobiotic-metabolizing P450s are especially
      well suited to such protein engineering due to their ability to interact with
      relatively wide ranges of substrates with marked differences in structure and
      physicochemical properties. Typical characteristics, such as the low turnover
      rates and poor coupling seen during the metabolism of xenobiotics, as well as the
      enzyme specificity towards particular substrates and reactions, can be improved
      by directed evolution. This mini-review will cover the fundamental enabling
      technologies required to successfully engineer P450s, examine the work done to
      date on the directed evolution of mammalian forms, and provide a perspective on
      what will be required for the successful implementation of engineered enzymes.

PMID- 17537394
TI  - Different signaling pathways utilized by insulin to regulate the expression of
      ENT2, CNT1, CNT2 nucleoside transporters in rat cardiac fibroblasts.
AB  - In cardiac fibroblasts (CFs), insulin was shown to affect the expression of ENT2,
      CNT1, and CNT2 transporter. In the present study, we determined the signaling
      pathways utilized by insulin to regulate the expression of these nucleoside
      transporters. In the primary culture of rat CFs, insulin increased the mRNA level
      of ENT2 and suppressed the CNT1 and CNT2 mRNA levels. The insulin-induced
      increase of the ENT2 mRNA level was blocked by rapamycin (an inhibitor of mTOR)
      and by cycloheximide (an inhibitor of protein synthesis), whereas neither
      wortmannin (an inhibitor of PI3K) nor PD98059 (an inhibitor of MEK) affected the
      insulin action on the ENT2 transcript level. PD98059 completely blocked the
      insulin-induced decrease of the CNT1 and CNT2 mRNAs levels. Wortmannin prevented
      the insulin-induced change of the CNT1 mRNA level, but had no effect on the CNT2
      mRNA. Rapamycin abolished the insulin effect on the CNT1 mRNA level, but not on
      the CNT2 mRNA. Cycloheximide prevented the insulin-induced decrease of CNT2 mRNA,
      but had no effect on the CNT1 mRNA level. Overall, our results demonstrate that
      the expression level of ENT2, CNT1, and CNT2 transporters in CFs is
      differentially regulated by insulin. Moreover, in this cell type insulin employs
      a distinct signaling pathway to regulate the expression of each transporter.

PMID- 17537395
TI  - A model for glutathione binding and activation in the fosfomycin resistance
      protein, FosA.
AB  - The genomically encoded fosfomycin resistance protein from Pseudomonas aeruginosa
      (FosA(PA)) utilizes Mn(II) and K(+) to catalyze the addition of glutathione (GSH)
      to C1 of the antibiotic rendering it inactive. Although this protein has been
      structurally and kinetically characterized with respect to the substrate,
      fosfomycin, questions remain regarding how the enzyme binds the thiol substrate,
      GSH. Computational studies have revealed a potential GSH binding site in FosA(PA)
      that involves six electrostatic or hydrogen-bonding interactions with protein
      side-chains as well as six additional residues that contribute van der Waals
      interactions. A strategically placed tyrosine residue, Y39, appears to be
      involved in the ionization of GSH during catalysis. The Y39F mutant exhibits a 13
      fold reduction of catalytic activity (k(cat)=14+/-2s(-1)), suggesting a role in
      the ionization of GSH. Mutation of five other residues (W34, Q36, S50, K90, and
      R93) implicated in ionic of hydrogen-bonding interactions resulted in enzymes
      with reduced catalytic efficiency, affinity for GSH, or both. The mutant enzymes
      were also found to be less effective resistant proteins in the biological context
      of Escherichia coli. The more conservative W34H mutant has native-like catalytic
      efficiency suggesting that the imidazole NH group can replace the indole group of
      W34 that is important for GSH binding. In the absence of co-crystal structural
      data with the thiol substrate, these results provide important insights into the
      role of GSH in catalysis.

PMID- 17537396
TI  - Effect of detergents, trypsin and unsaturated fatty acids on latent loquat fruit
      polyphenol oxidase: basis for the enzyme's activity regulation.
AB  - The effects of detergents, trypsin and fatty acids on structural and functional
      properties of a pure loquat fruit latent polyphenol oxidase have been studied in
      relation to its regulation. Anionic detergents activated PPO at pH 6.0 below
      critical micelle concentration (cmc), but inhibited at pH 4.5 well above cmc.
      This behavior is due to a detergent-induced pH profile alkaline shift,
      accompanied by changes of intrinsic fluorescence of the protein. Gel filtration
      experiments demonstrate the formation of PPO-SDS mixed micelles. Partial PPO
      proteolysis suggest that latent PPO losses an SDS micelle-interacting region but
      conserves an SDS monomer-interacting site. Unsaturated fatty acids inhibit PPO at
      pH 4.5, the strongest being linolenic acid while the weakest was gamma-linolenic
      acid for both, the native and the trypsin-treated PPO. Down-regulation of PPO
      activity by anionic amphiphiles is discussed based on both, the pH profile shift
      induced upon anionic amphiphile binding and the PPO interaction with negatively
      charged membranes.

PMID- 17537397
TI  - Characterization and comparison of the intronic promoter of murine osteoclastic
      protein-tyrosine phosphatase, PTP-oc, with the human PTP-oc promoter.
AB  - This study characterized the murine osteoclastic protein-tyrosine phosphatase
      (PTP-oc) promoter located within intron 12 of the Glepp1 gene. A 2-kb DNA
      fragment containing the putative intronic promoter showed strong promoter
      activity in pre-osteoclastic RAW264.7 and U937 cells, but not in non-osteoclastic
      cells. Deletion analyses identified a proximal region with elements required for
      basal activity, and upstream repressor and enhancer elements. The cell-type
      specificity of the promoter was conferred by upstream domains. At least nine
      conserved response elements, with potential transcription factor binding sites,
      were identified in both human and murine promoters. EMSA and ChIP indicate the
      presence of occupied binding sites for Pit-1a, Ikaros-1/2, and D1DR transcription
      factors in the murine promoter. Site-directed mutagenesis of response elements
      resulted in down- or up-regulation of promoter activity: some of the effects were
      different between the murine and human promoter, suggesting that there may be
      inter-species differences in the regulation of the PTP-oc promoter.

PMID- 17537399
TI  - DNA induces folding in alpha-synuclein: understanding the mechanism using
      chaperone property of osmolytes.
AB  - Alpha-synuclein conformational modulation leading to fibrillation has been
      centrally implicated in Parkinson's disease. Previously, we have shown that alpha
      synuclein has DNA binding property. In the present study, we have characterized
      the effect of DNA binding on the conformation and fibrillation kinetics of alpha
      synuclein. It was observed that single-stranded circular DNA induce alpha-helix
      conformation in alpha-synuclein while plasmid supercoiled DNA has dual effect
      inducing a partially folded conformation and alpha-helix under different
      experimental conditions. Interestingly, alpha-synuclein showed a specificity for
      GC* nucleotide sequence in its binding ability to DNA. The aggregation kinetics
      data showed that DNA which induced partially folded conformation in alpha
      synuclein promoted the fibrillation while DNA which induced alpha-helix delayed
      the fibrillation, indicating that the partially folded intermediate conformation
      is critical in the aggregation process. Further, the mechanism of DNA-induced
      folding/aggregation of alpha-synuclein was studied using effect of osmolytes on
      alpha-synuclein as a model system. Among the five osmolytes used, Glycerol,
      trimethylamine-N-oxide, Betaine, and Taurine induced partially folded
      conformation and in turn enhanced the aggregation of alpha-synuclein. The ability
      of DNA and osmolytes in inducing conformational transition in alpha-synuclein,
      indicates that two factors are critical in modulating alpha-synuclein folding:
      (i) electrostatic interaction as in the case of DNA, and (ii) hydrophobic
      interactions as in the case of osmolytes. The property of DNA inducing alpha
      helical conformation in alpha-synuclein and inhibiting the fibrillation may be of
      significance in engineering DNA-chip based therapeutic approaches to PD and other
      amyloid disorders.

PMID- 17537398
TI  - Human aldo-keto reductases: Function, gene regulation, and single nucleotide
      polymorphisms.
AB  - Aldo-keto reductases (AKRs) are a superfamily of NAD(P)H linked oxidoreductases
      that are generally monomeric 34-37kDa proteins present in all phyla. The
      superfamily consists of 15 families, which contains 151 members
      (www.med.upenn.edu/akr). Thirteen human AKRs exist that use endogenous substrates
      (sugar and lipid aldehydes, prostaglandins, retinals and steroid hormones), and
      in many instances they regulate nuclear receptor signaling. Exogenous substrates
      include metabolites implicated in chemical carcinogenesis: NNK (4
      (methylnitrosamino)-1-(3-pyridyl)-1-butanone), polycyclic aromatic hydrocarbon
      trans-dihydrodiols, and aflatoxin dialdehyde. Promoter analysis of the human
      genes identifies common elements involved in their regulation which include
      osmotic response elements, anti-oxidant response elements, xenobiotic response
      elements, AP-1 sites and steroid response elements. The human AKRs are highly
      polymorphic, and in some instances single nucleotide polymorphisms (SNPs) of high
      penetrance exist. This suggests that there will be inter-individual variation in
      endogenous and xenobiotic metabolism which in turn affect susceptibility to
      nuclear receptor signaling and chemical carcinogenesis.

PMID- 17537401
TI  - Decrease of elastic moduli of DOPC bilayers induced by a macrolide antibiotic,
      azithromycin.
AB  - The elastic properties of membrane bilayers are key parameters that control its
      deformation and can be affected by pharmacological agents. Our previous atomic
      force microscopy studies revealed that the macrolide antibiotic, azithromycin,
      leads to erosion of DPPC domains in a fluid DOPC matrix [A. Berquand, M. P.
      Mingeot-Leclercq, Y. F. Dufrene, Real-time imaging of drug-membrane interactions
      by atomic force microscopy, Biochim. Biophys. Acta 1664 (2004) 198-205.]. Since
      this observation could be due to an effect on DOPC cohesion, we investigated the
      effect of azithromycin on elastic properties of DOPC giant unilamellar vesicles
      (GUVs). Microcinematographic and morphometric analyses revealed that azithromycin
      addition enhanced lipid membranes fluctuations, leading to eventual disruption of
      the largest GUVs. These effects were related to change of elastic moduli of DOPC,
      quantified by the micropipette aspiration technique. Azithromycin decreased both
      the bending modulus (k(c), from 23.1+/-3.5 to 10.6+/-4.5 k(B)T) and the apparent
      area compressibility modulus (K(app), from 176+/-35 to 113+/-25 mN/m). These data
      suggested that insertion of azithromycin into the DOPC bilayer reduced the
      requirement level of both the energy for thermal fluctuations and the stress to
      stretch the bilayer. Computer modeling of azithromycin interaction with DOPC
      bilayer, based on minimal energy, independently predicted that azithromycin (i)
      inserts at the interface of phospholipid bilayers, (ii) decreases the energy of
      interaction between DOPC molecules, and (iii) increases the mean surface occupied
      by each phospholipid molecule. We conclude that azithromycin inserts into the
      DOPC lipid bilayer, so as to decrease its cohesion and to facilitate the merging
      of DPPC into the DOPC fluid matrix, as observed by atomic force microscopy. These
      investigations, based on three complementary approaches, provide the first
      biophysical evidence for the ability of an amphiphilic antibiotic to alter lipid
      elastic moduli. This may be an important determinant for drug: lipid interactions
      and cellular pharmacology.

PMID- 17537400
TI  - MMP gene polymorphisms as contributors for cleft lip/palate: association with
      MMP3 but not MMP1.
AB  - OBJECTIVE: Orofacial clefts result from failures of developing embryonic facial
      and palatal processes to either completely merge or fuse. Normal development of
      the facial primordia requires remodelling of the extracellular matrix, which is
      mediated in part by the matrix metalloproteinases (MMPs). MMPs can be considered
      a group of candidate proteins for the etiology of cleft lip with or without cleft
      palate (CL/P) due to their role in craniofacial modelling. The purpose of this
      study was to determine if polymorphisms in MMP1 and MMP3 gene promoters were
      associated with CL/P. DESIGN: DNA was extracted from buccal epithelial cells and
      genotypes were obtained from CL/P cases and controls through PCR with allele
      specific primers (MMP3, n=333) and restriction-fragment length polymorphism
      techniques (MMP1, n=395). RESULTS: Significant differences between cases and
      controls were observed for MMP3 [5A/6A allele frequencies (p=0.00001) and
      genotype frequencies (p=0.00001)]; and between cleft types and controls
      (p=0.00001 for CL/P; p=0.04 for CP). No significant differences were found for
      MMP1 allele and genotype frequencies between cases and controls or between cleft
      types and controls. CONCLUSIONS: An association between a polymorphism in MMP3
      gene and CL/P has been observed. Although the extent to which this polymorphism
      may actually contribute to the affected cleft status is yet to be clarified,
      polymorphisms of MMP genes may be good candidates as genetic factors for their
      role in active ECM remodelling.

PMID- 17537402
TI  - Anxiety sensitivity and intolerance of uncertainty: requisites of the fundamental
      fears?
AB  - Fears related to anxiety sensitivity (AS)-illness/injury sensitivity, fear of
      negative evaluation, and fear of pain-may have important theoretical associations
      with intolerance of uncertainty (IU). In separate investigations, AS and IU have
      been independently related to the same anxiety-related psychopathology. AS and IU
      seem to share a basis in fearing unknown, potentially harmful consequences;
      however, their inter-relationship remains uncertain. IU regarding a specific
      stimulus, a physical sensation for example, may result in a variety of
      interpretations and responses, including the catastrophic appraisals that
      characterize AS. The association between AS and IU was examined in a sample of
      293 undergraduates. Results of confirmatory factor and correlation analyses
      suggest the two constructs are related, but nonetheless independent. It appears
      that IU may be a required component of catastrophic misappraisals while being an
      important construct related to fear and anxiety in its own right. Future research
      directions and potential applications are discussed.

PMID- 17537403
TI  - Identification of apoptosis-related PLZF target genes.
AB  - The PLZF gene encodes a BTB/POZ-zinc finger-type transcription factor, involved
      in physiological development, proliferation, differentiation, and apoptosis. In
      this paper, we investigate proliferation, survival, and gene expression
      regulation in stable clones from the human haematopoietic K562, DG75, and Jurkat
      cell lines with inducible expression of PLZF. In Jurkat cells, but not in K562
      and DG75 cells, PLZF induced growth suppression and apoptosis in a cell density
      dependent manner. Deletion of the BTB/POZ domain of PLZF abrogated growth
      suppression and apoptosis. PLZF was expressed with a nuclear speckled pattern
      distinctively in the full-length PLZF-expressing Jurkat clones, suggesting that
      the nuclear speckled localization is required for PLZF-induced apoptosis. By
      microarray analysis, we identified that the apoptosis-inducer TP53INP1, ID1, and
      ID3 genes were upregulated, and the apoptosis-inhibitor TERT gene was
      downregulated. The identification of apoptosis-related PLZF target genes may have
      biological and clinical relevance in cancer typified by altered PLZF expression.

PMID- 17537404
TI  - Drug resistance to 5-FU linked to reactive oxygen species modulator 1.
AB  - While acute oxidative stress triggers cell apoptosis or necrosis, persistent
      oxidative stress induces genomic instability and has been implicated in tumor
      progression and drug resistance. In a previous report, we demonstrated that
      reactive oxygen species modulator 1 (Romo1) expression was up-regulated in most
      cancer cell lines and suggested that increased Romo1 expression might confer
      chronic oxidative stress to tumor cells. In this study, we show that enforced
      Romo1 expression induces reactive oxygen species (ROS) production in the
      mitochondria leading to massive cell death. However, tumor cells that adapt to
      oxidative stress by increasing manganese superoxide dismutase (MnSOD), Prx I, and
      Bcl-2 showed drug resistance to 5-FU. To elucidate the relationship between 5-FU
      induced ROS production and Romo1 expression, Romo1 siRNA was used to inhibit 5-FU
      triggered Romo1 induction. Romo1 siRNA treatment efficiently blocked 5-FU-induced
      ROS generation, demonstrating that 5-FU treatment stimulated ROS production
      through Romo1 induction. Based on these results we suggest that cellular adaptive
      response to Romo1-induced ROS is another mechanism of drug resistance to 5-FU and
      Romo1 expression may provide a new clinical implication in drug resistance of
      cancer chemotherapy.

PMID- 17537405
TI  - Selection of antigenic markers on a GFP-Ckappa fusion scaffold with high
      sensitivity by eukaryotic ribosome display.
AB  - Ribosome display is a cell-free system permitting gene selection through the
      physical association of genetic material (mRNA) and its phenotypic (protein)
      product. While often used to select single-chain antibodies from large libraries
      by panning against immobilized antigens, we have adapted ribosome display for use
      in the 'reverse' format in order to select high affinity antigenic determinants
      against solid-phase antibody. To create an antigenic scaffold, DNA encoding green
      fluorescent protein (GFP) was fused to a light chain constant domain (Ckappa)
      with stop codon deleted, and with 5' signals (T7 promoter, Kozak) enabling
      coupled transcription/translation in a eukaryotic cell-free system. Epitopes on
      either GFP (5') or Ckappa (3') were selected by anti-GFP or anti-Ckappa
      antibodies, respectively, coupled to magnetic beads. After selection, mRNA was
      amplified directly from protein-ribosome-mRNA (PRM) complexes by in situ PCR
      followed by internal amplification and reassembly PCR. As little as 10fg of the
      1kb DNA construct, i.e. approximately 7500 molecules, could be recovered
      following a single round of interaction with solid-phase anti-GFP antibody. This
      platform is highly specific and sensitive for the antigen-antibody interaction
      and may permit selection and reshaping of high affinity antigenic variants of
      scaffold proteins.

PMID- 17537406
TI  - Molecular mechanism of alpha-tocopheryl-phosphate transport across the cell
      membrane.
AB  - alpha-Tocopheryl-phosphate (alpha-TP) is synthesized and hydrolyzed in animal
      cells and tissues where it modulates several functions. alpha-TP is more potent
      than alpha-T in inhibiting cell proliferation, down-regulating CD36
      transcription, inhibiting atherosclerotic plaque formation. Administration of
      alpha-TP to cells or animals requires its transfer through membranes, via a
      transporter. We show here that alpha-TP is passing the plasma membrane via a
      system that is inhibited by glibenclamide and probenecid, inhibitors of a number
      of transporters. Glibenclamide and probenecid prevent dose-dependently alpha-TP
      inhibition of cell proliferation. The two inhibitors act on ATP binding cassette
      (ABC) and organic anion transporters (OAT). Since ABC transporters function to
      export solutes and alpha-TP is transported into cells, it may be concluded that
      alpha-TP transport may occur via an OAT family member. Due to the protection by
      glibenclamide and probenecid on the alpha-TP induced cell growth inhibition it
      appears that alpha-TP acts after its uptake inside cells.

PMID- 17537407
TI  - Cell selective glucocorticoid induction of caveolin-1 and caveolae in
      differentiating pulmonary alveolar epithelial cell cultures.
AB  - Increased caveolin-1 expression is a marker of the differentiation of lung
      alveolar epithelial type II cells into a type I phenotype. Here, we show in both
      a primary differentiating rat alveolar culture, and a human alveolar cell line
      (A549) that caveolae formation and caveolin-1 expression are dependent upon
      dexamethasone Dex, and is inhibited by the glucocorticoid receptor (GR)
      antagonist, mifepristone. Study of a panel of 20 different cell types showed the
      effect of (Dex) upon caveolin-1 expression to be highly cell selective for lung
      alveolar epithelial cells. The actions of glucocorticoid upon caveolin-1 appear
      indirect acting via intermediary genes as evidenced by cycloheximide (CHX)
      abolition of Dex-induced increases in caveolin-1 mRNA and by recombinant
      transfection studies using the caveolin-1 promoter cloned upstream of a reporter
      gene. Treatment with actinomycin D (ACD) revealed that the effects of Dex are
      also, at least in part, mediated by stabilisation of caveolin-1 mRNA.
      Collectively, these results indicate that glucocorticoids modulate the expression
      of caveolin-1 and caveolae biogenesis within alveolar epithelial cells via both
      transcriptional and translational modifications. The cell-selective effects of
      glucocorticoid upon caveolin may represent a previously unrecognised mechanism by
      which glucocorticoids affect lung development.

PMID- 17537408
TI  - Osteopontin is a myosphere-derived secretory molecule that promotes angiogenic
      progenitor cell proliferation through the phosphoinositide 3-kinase/Akt pathway.
AB  - We have reported that skeletal myosphere-derived progenitor cells (MDPCs) can
      differentiate into vascular cells, and that MDPC transplantation into
      cardiomyopathic hearts improves cardiac function. However, the
      autocrine/paracrine molecules and underlying mechanisms responsible for MDPC
      growth have not yet been determined. To explore the molecules enhancing the
      proliferation of MDPCs, we performed serial analysis of gene expression and
      signal sequence trap methods using RNA isolated from MDPCs. We identified
      osteopontin (OPN), a secretory molecule, as one of most abundant molecules
      expressed in MDPCs. OPN provided a proliferative effect for MDPCs. MDPCs treated
      with OPN showed Akt activation, and inhibition of the phosphoinositide 3-kinase
      (PI3K)/Akt pathway repressed the proliferative effect of OPN. Furthermore, OPN
      pretreated MDPCs maintained their differentiation potential into endothelial and
      vascular smooth muscle cells. These findings indicate an important role of OPN as
      an autocrine/paracrine molecule in regulating the proliferative growth of muscle
      derived angiogenic progenitor cells via the PI3K/Akt pathway.

PMID- 17537409
TI  - The complex etiology of multiple sclerosis.
AB  - Multiple sclerosis is a demyelinating disease which is presumed to be a
      consequence of infiltrating lymphocytes autoreactive to myelin proteins. This is
      substantiated by several lines of clinical evidence and supported by correlative
      studies in preclinical models. The development of new therapeutics for MS has
      been guided by this perspective; however, the pathogenesis of MS has proven to be
      quite complex as observations exist which question the role of autoreactive
      lymphocytes in the etiology of MS. In addition the current immunomodulatory
      therapeutics do not prevent most patients from progressing into more serious
      forms of the disease. The development of truly transformational therapeutics for
      MS will likely require a broad assault that expands beyond the concept of MS
      being an autoimmune disease.

PMID- 17537410
TI  - Human primary brain tumor cell growth inhibition in serum-free medium optimized
      for neuron survival.
AB  - Glioblastoma is the most common primary brain tumor in adults from which about
      15,000 patients die each year in the United States. Despite aggressive surgery,
      radiotherapy and chemotherapy, median survival remains only 1 year. Here we
      evaluate growth of primary human brain tumor cells in a defined nutrient culture
      medium (Neuregen) that was optimized for neuron regeneration. We hypothesized
      that Neuregen would inhibit tumor cell growth because of its ability to inhibit
      gliosis in rat brain. Tumor tissue was collected from 18 patients including 10
      males and 8 females (mean age 60+/-12 years) who underwent craniotomy for newly
      diagnosed, histologically confirmed brain tumors. The tissue was shipped
      overnight in Hibernate transport medium. Tumor cells were isolated and plated in
      Neurobasal/serum or Neuregen on culture plastic. After 1 week, growth in Neuregen
      was significantly less in 9/10 glioblastoma multiforme cases, 5/5 meningioma
      cases and 3/3 cases of brain metastasis. Analysis of deficient formulations of
      Neuregen and formulations to which selected components were added back implicate
      no single active component. However, individual cases were sensitive to
      corticosterone, selenium, ethanolamine, fatty acids and/or antioxidants.
      Therefore, a defined culture medium that promotes neuron regeneration inhibits
      the growth of human primary glioblastoma, meningioma and metastatic tumor cells
      in culture. The possible in vivo efficacy of Neuregen for treatment of brain
      tumor resections remains to be determined.

PMID- 17537411
TI  - Swim training sensitizes myocardial response to insulin: role of Akt-dependent
      eNOS activation.
AB  - OBJECTIVES: Physical activity has been well known to benefit heart function. The
      improved autonomic nervous activity is considered to be mainly responsible for
      this beneficial effect. However, the precise mechanism behind the intrinsic
      myocardial responsiveness to exercise is still unclear. This study was designed
      to examine the effect of swim training on myocardial response to insulin with a
      special focus on the endogenous endothelial nitric oxide synthase (eNOS)-nitric
      oxide (NO) cascade. METHODS: Adult male Sprague-Dawley (SD) rats were subjected
      to a 10-week free-loading swim training (3 h/day, 5 days/week). Contractile
      response to insulin at the levels of cardiomyocytes and isolated perfused heart,
      myocardial glucose uptake and post-insulin receptor signaling cascades were
      evaluated. RESULTS: Swim training enhanced cardiac contractile response to
      insulin in cardiomyocytes and isolated perfused heart, respectively. The improved
      cardiac response was accompanied by facilitated insulin-stimulated glucose
      uptake, GLUT4 translocation and upregulation of Akt and eNOS expression (p<0.01).
      Treatment with insulin resulted in a 3.6- and 2.2-fold increase of eNOS
      phosphorylation (p<0.01), as well as a 3.0- and 1.9-fold increase of Akt
      phosphorylation in exercise and sedentary groups, respectively (p<0.01). In
      addition, exercise significantly facilitated insulin-induced myocardial NO
      production (p<0.01 vs. sedentary). Moreover, pretreatment with either LY294002, a
      phosphatidylinositol-3 kinase (PI-3K) inhibitor or L-NAME, a NOS inhibitor,
      abolished the exercise-induced sensitization of myocardial contractile response
      to insulin, insulin-induced NO production and phosphorylation of Akt and eNOS.
      CONCLUSION: These results demonstrate that swim training is capable of
      sensitizing myocardial contractile response to insulin via upregulation of Akt-
      and eNOS signaling cascades.

PMID- 17537412
TI  - Lindane may modulate the female reproductive development through the interaction
      with ER-beta: an in vivo-in vitro approach.
AB  - Lindane (gamma-HCH) is a persistent environmental pollutant that may act as
      endocrine disrupter, affecting the nervous, immune and reproductive system,
      possibly through endocrine-mediated mechanisms. Since both estrogen receptors (ER
      alpha and -beta) have shown to be target for endocrine disruption, we
      investigated the role of gamma-HCH on the development of female reproductive
      system. For an in vivo evaluation of gamma-HCH effects during prenatal period,
      pregnant CD1 mice were treated p.o. on gestational days 9-16 with 15 mg/kg bw/day
      of gamma-HCH and vehicle. The in vivo findings in treated F1 pups - in the
      absence of signs of systemic toxicity - included increase in the absolute and
      relative and absolute uterus weight revealed on post-natal day 22, earlier
      vaginal patency and reduced diameters of primary oocytes at fully sexual
      maturity. No effects on steroid hormone metabolism (aromatase, testosterone
      catabolism) were observed. Thus, gamma-HCH elicited subtle effects on female
      reproductive development likely mediated by ER-beta-mediated pathway(s), without
      a concurrent impairment of steroid hormone metabolism. Furthermore, to verify
      whether the endocrine interference of gamma-HCH is attributable to stimulation of
      ER-beta-mediated pathway(s), its effect has been evaluated in vitro on a cell
      line, LNCaP, expressing only functional ER-beta. In vitro treatments revealed a
      concentration-related effect on LNCaP cell viability and proliferation.
      Significantly, the contemporary addition of a pure anti-estrogen, the ER
      antagonist ICI 182,780, completely reversed gamma-HCH effects indicating an ER
      beta-mediated action. Our findings indicate that gamma-HCH may act as endocrine
      disruptor during the female reproductive system development and ER-beta as a
      potential target for this compound and other endocrine disrupting chemicals as
      well.

PMID- 17537413
TI  - Beneficial effect of succinic acid monoethyl ester on erythrocyte membrane bound
      enzymes and antioxidant status in streptozotocin-nicotinamide induced type 2
      diabetes.
AB  - Succinic acid monoethyl ester (EMS) was recently proposed as an insulinotropic
      agent for the treatment of non-insulin dependent diabetes mellitus. In the
      present study the effect of EMS and metformin on erythrocyte membrane bound
      enzymes and antioxidants activity in plasma and erythrocytes of streptozotocin
      nicotinamide induced type 2 diabeteic model was investigated. Succinic acid
      monoethyl ester was administered intraperitonially for 30 days to control and
      diabetic rats. The effect of EMS on glucose, insulin, hemoglobin, glycosylated
      hemoglobin, TBARS, hydroperoxide, superoxide dismutase (SOD), catalase (CAT),
      glutathione peroxide (Gpx), glutathione-S-transferase (GST), vitamins C and E,
      reduced glutathione (GSH) and membrane bound enzymes were studied. The effect of
      EMS was compared with metformin, a reference drug. The levels of glucose,
      glycosylated hemoglobin, TBARS, hyderoperoxide, and vitamin E were increased
      significantly whereas the level of insulin and hemoglobin, as well as
      antioxidants (SOD, CAT, Gpx, GST, vitamin C and GSH) membrane bound total ATPase,
      Na(+)/K(+)-ATPase, Ca(2+)-ATPase and Mg(2+)-ATPase were decreased significantly
      in streptozotocin-nicotinamide diabetic rats. Administration of EMS to diabetic
      rats showed a decrease in the levels of glucose, glycosylated hemoglobin, lipid
      peroxidation markers and vitamin E. In addition the levels of insulin,
      hemoglobin, enzymic antioxidants, vitamin C, and GSH and the activities of
      membrane bound enzymes also were increased in EMS and metformin treated diabetic
      rats. The present study indicates that the EMS possesses a significant beneficial
      effect on erythrocyte membrane bound enzymes and antioxidants defense system in
      addition to its antidiabetic effect.

PMID- 17537414
TI  - The role of epithelial-mesenchymal transition in oral squamous cell carcinoma and
      oral submucous fibrosis.
AB  - Epithelial-mesenchymal transition (EMT) is an indispensable mechanism during
      morphogenesis. Interest and research in EMT are currently at a high level due to
      its important role in cancer and fibrosis. Emerging evidence suggests that EMT is
      also a crucial event in oral squamous cell carcinoma (OSCC). Oral submucous
      fibrosis (OSF) is a chronic debilitating disease and a premalignant condition of
      the oral cavity. It is characterized by a generalized submucosal fibrosis. The
      pathogenesis of the disease is not well established. Epidemiological evidence
      strongly indicates an association between the betel quid (BQ) chewing habit and
      OSF. In a simplistic view, OSF represents a failed wound-healing process of the
      oral mucosa after chronic, sustained injury. This review highlights the signaling
      pathways involved in EMT, recent advances in the study of EMT in OSCC, and
      summarizes the evidence supporting a role for EMT in the pathogenesis of OSF.

PMID- 17537415
TI  - Serum IL-16, not IL-15, was elevated in early second trimester of pregnancy in
      women who subsequently developed preeclampsia.

PMID- 17537416
TI  - Increased urinary cystatin C reflects structural and functional renal tubular
      impairment independent of glomerular filtration rate.
AB  - OBJECTIVES: The ratio of the urinary mass concentrations of cystatin C and
      creatinine (UcysC/Ucrea)>/=11.3 mg/mmol has recently been proposed as an accurate
      marker for the detection of GFR</=60 mL/min/1.73 m(2). DESIGN AND METHODS: We
      prospectively evaluated the diagnostic performance of UcysC/Ucrea>/=11.3 mg/mmol
      and factors associated with increased UcysC/Ucrea in 72 children and adults with
      a wide variety of renal disorders. UcysC/Ucrea was calculated, and GFR wad
      estimated from serum creatinine and cystatin C by equations. RESULTS:
      UcysC/Ucrea>/=11.3 mg/mmol had a low diagnostic value to detect GFR values</=60
      mL/min/1.73 m(2) estimated by creatinine or cystatin-C-based equations with
      sensitivities of 72% and 63%, and specificities of 42% and 34%. ROC curves for
      UcysC/Ucrea to detect GFR</=60 mL/min/1.73 m(2) confirmed this with AUCs of 0.59
      for creatinine and 0.57 for cystatin-C-based equations. Multivariate analysis
      identified tubular proteinuria, tubulointerstitial disease and heavy proteinuria,
      but not GFR</=60 mL/min/1.73 m(2), as factors independently associated with
      increased UcysC/Ucrea. CONCLUSIONS: UcysC/Ucrea>/=11.3 mg/mmol is not an accurate
      marker to detect GFR</=60 mL/min/1.73 m(2), but reflects tubular dysfunction and
      proteinuria due to heavy proteinuria and tubulointerstitial disease.

PMID- 17537417
TI  - How grammar can cope with limited short-term memory: simultaneity and seriality
      in sign languages.
AB  - It is known that in American Sign Language (ASL) span is shorter than in English,
      but this discrepancy has never been systematically investigated using other pairs
      of signed and spoken languages. This finding is at odds with results showing that
      short-term memory (STM) for signs has an internal organization similar to STM for
      words. Moreover, some methodological questions remain open. Thus, we measured
      span of deaf and matched hearing participants for Italian Sign Language (LIS) and
      Italian, respectively, controlling for all the possible variables that might be
      responsible for the discrepancy: yet, a difference in span between deaf signers
      and hearing speakers was found. However, the advantage of hearing subjects was
      removed in a visuo-spatial STM task. We attribute the source of the lower span to
      the internal structure of signs: indeed, unlike English (or Italian) words, signs
      contain both simultaneous and sequential components. Nonetheless, sign languages
      are fully-fledged grammatical systems, probably because the overall architecture
      of the grammar of signed languages reduces the STM load. Our hypothesis is that
      the faculty of language is dependent on STM, being however flexible enough to
      develop even in a relatively hostile environment.

PMID- 17537418
TI  - Ape metaphysics: object individuation without language.
AB  - Developmental research suggests that whereas very young infants individuate
      objects purely on spatiotemporal grounds, from (at latest) around 1 year of age
      children are capable of individuating objects according to the kind they belong
      to and the properties they instantiate. As the latter ability has been found to
      correlate with language, some have speculated whether it might be essentially
      language dependent and therefore uniquely human. Existing studies with non-human
      primates seem to speak against this hypothesis, but fail to present conclusive
      evidence due to methodological shortcomings. In the present experiments we set
      out to test non-linguistic object individuation in three great ape species with a
      refined manual search methodology. Experiment 1 tested for spatiotemporal object
      individuation: Subjects saw 1 or 2 objects simultaneously being placed inside a
      box in which they could reach, and then in both conditions only found 1 object.
      After retrieval of the 1 object, subjects reached again significantly more often
      when they had seen 2 than when they had seen 1 object. Experiment 2 tested for
      object individuation according to property/kind information only: Subjects saw 1
      object being placed inside the box, and then either found that object (expected)
      or an object of a different kind (unexpected). Analogously to Experiment 1, after
      retrieval of the 1 object, subjects reached again significantly more often in the
      unexpected than in the expected condition. These results thus confirm previous
      findings suggesting that individuating objects according to their property/kind
      is neither uniquely human nor essentially language dependent. It remains to be
      seen, however, whether this kind of object individuation requires sortal concepts
      as human linguistic thinkers use them, or whether some simpler form of tracking
      properties is sufficient.

PMID- 17537419
TI  - Cognitive control acts locally.
AB  - Cognitive control adjusts information processing to momentary needs and task
      requirements. We investigated conflict adaptation when participants are
      performing two tasks, a Simon task and a SNARC task. The results indicated that
      one congruency effect (e.g., Simon) was reduced after conflict in the other task
      (e.g., SNARC), but only when both tasks used identical relevant information. On
      the other hand, when both tasks used different relevant information, a larger
      congruency effect was observed after conflict in the other task. The results are
      explained in terms of a local control mechanism.

PMID- 17537420
TI  - An information-based approach to action understanding.
AB  - It has been proposed that the ability to make sense of other agents' behavior
      relies on the activation of internal mechanisms that map action perception onto
      action execution. In this study we explored the constraints on this ability
      introduced by eyeheight-scaled information in the optic array. Short and tall
      participants provided maximum overhead reaching judgments for themselves and
      another participant. Perceptual information was manipulated by changing the
      participants' optically specified eyeheight. Observers were modestly accurate in
      perceiving maximum overhead reach for themselves and for another actor whose
      action capabilities differed. Perceived maximum overhead reach increased for both
      self- and other-judgments when the perceiver's eyeheight was increased. The
      results suggest an important role of perceptual information that has gone
      unrecognized in existing accounts of action understanding and prediction.

PMID- 17537422
TI  - Mandarin learners use syntactic bootstrapping in verb acquisition.
AB  - Mandarin Chinese allows pervasive ellipsis of noun arguments (NPs) in discourse,
      which casts doubt concerning child learners' use of syntax in verb learning. This
      study investigated whether Mandarin learning children would nonetheless extend
      verb meanings based on the number of NPs in sentences. Forty-one Mandarin
      speaking two- and three-year-olds enacted sentences with familiar motion verbs.
      The presence of an extra postverbal NP led the toddlers to extend causative
      meanings to intransitive verbs, and the absence of a postverbal NP led them to
      extend noncausative meanings to transitive verbs. The effects of adding or
      subtracting an NP were statistically indistinguishable. Thus, the number of NPs
      in a sentence appears to play a role in verb learning in Mandarin Chinese.

PMID- 17537423
TI  - Cryotolerance of Lactobacillus delbrueckii subsp. bulgaricus CFL1 is modified by
      acquisition of antibiotic resistance.
AB  - This study aimed to relate the acquisition of different antibiotic resistances
      and the corresponding physiological responses to cold stress of Lactobacillus
      delbrueckii subsp. bulgaricus strain CFL1. Six resistant mutants were
      spontaneously obtained and studied depending on the target of the antibiotic: (i)
      bacitracin and vancomycin (Bac(R), Van(R), wall synthesis), (ii) novobiocin
      (Nov(R), DNA replication), and (iii) kanamycin, spiramycin, streptomycin (Kan(R),
      Spi(R), Str(R), RNA translation). The mutations modified the growth and the cold
      stress response at three different physiological levels: (i) Van(R) and Spi(R)
      mutants showed significant lower growth rates compared to the wild type strain.
      (ii) Van(R) and Bac(R) mutants displayed a slightly higher resistance to a
      freezing-thawing challenge whereas Str(R) and Spi(R) mutants were more sensitive
      compared to the wild type. (iii) The recovery of acidification activity after
      freezing and during frozen storage was improved by considering the Nov(R) strain,
      but not with the Van(R) and Spi(R) mutants. Thus, acquisition of some antibiotic
      resistance by spontaneous mutation led to modification of the cold stress
      response. The hypothesis of a unique cellular thermostat is discussed regarding
      the diversity of the tested antibiotics.

PMID- 17537425
TI  - The effect of mustard gas on the biological activity of soil.
AB  - A special group of substances that are very dangerous for the biosphere includes
      war gases such as mustard gas (bis(2-chloroethyl)sulphide). The influence of
      mustard gas hydrolysis products (MGHPs) on soil microbiota has been investigated.
      These substances bear numerous toxic effects on soil microorganisms. They change
      significantly the number and the specific composition of soil microbiota and
      inhibit the enzyme activity of soils. The main "ecological targets" of mustard
      and its hydrolysis products' toxic action have been determined. MGHPs affect the
      growth and reproduction of soil micromycetes, as well as their morphological and
      cultural properties. Increase in number and size of mitochondria in the fungal
      cells is accompanied by increase in dehydrogenases activity. Cell permeability
      influenced by MGHPs grows in connection with concentration of toxicants. Increase
      of permeability corresponds to growth of the amount of unsaturated fatty acids.
      The changes in the fatty acid composition of lipids in the cells of the soil
      micromycetes display their adaptation to adverse impact of the substances
      studied. MGHPs and thiodiglycol enhance synthesis of polysaccharides and
      pigments.

PMID- 17537424
TI  - The MARVEL domain protein, Singles Bar, is required for progression past the pre
      fusion complex stage of myoblast fusion.
AB  - Multinucleated myotubes develop by the sequential fusion of individual myoblasts.
      Using a convergence of genomic and classical genetic approaches, we have
      discovered a novel gene, singles bar (sing), that is essential for myoblast
      fusion. sing encodes a small multipass transmembrane protein containing a MARVEL
      domain, which is found in vertebrate proteins involved in processes such as tight
      junction formation and vesicle trafficking where--as in myoblast fusion--membrane
      apposition occurs. sing is expressed in both founder cells and fusion competent
      myoblasts preceding and during myoblast fusion. Examination of embryos injected
      with double-stranded sing RNA or embryos homozygous for ethane methyl sulfonate
      induced sing alleles revealed an identical phenotype: replacement of
      multinucleated myofibers by groups of single, myosin-expressing myoblasts at a
      stage when formation of the mature muscle pattern is complete in wild-type
      embryos. Unfused sing mutant myoblasts form clusters, suggesting that early
      recognition and adhesion of these cells are unimpaired. To further investigate
      this phenotype, we undertook electron microscopic ultrastructural studies of
      fusing myoblasts in both sing and wild-type embryos. These experiments revealed
      that more sing mutant myoblasts than wild-type contain pre-fusion complexes,
      which are characterized by electron-dense vesicles paired on either side of the
      fusing plasma membranes. In contrast, embryos mutant for another muscle fusion
      gene, blown fuse (blow), have a normal number of such complexes. Together, these
      results lead to the hypothesis that sing acts at a step distinct from that of
      blow, and that sing is required on both founder cell and fusion-competent
      myoblast membranes to allow progression past the pre-fusion complex stage of
      myoblast fusion, possibly by mediating fusion of the electron-dense vesicles to
      the plasma membrane.

PMID- 17537426
TI  - Nano-aluminum: transport through sand columns and environmental effects on plants
      and soil communities.
AB  - Nano-aluminum is being used in increasing quantities as energetic material. This
      research addresses the transport of two types of nanosized aluminum particles
      (with aluminum oxide, or carboxylate ligand coating, Alex and L-Alex,
      respectively) through sand columns along with associated environmental impacts on
      soil systems. Surface phenomena and pH are variables controlling the transport of
      nano-aluminum particles through porous media. pH environment controls solubility
      and electrostatic interactions between nano-aluminum particles and porous media.
      (i.e., changes in point of zero charge, agglomeration, etc.). Concentrations (up
      to 17 mg/L) far greater than the World Health Organization guideline for Al in
      drinking water (0.2 mg/L) were measured in columns' leachates. Plant uptake
      studies, mineralization of radiolabeled glucose test and Microtox test were used
      to investigate the environmental impacts of nano-aluminum on soil communities and
      plants. It appears that the presence of nano-aluminum particles did not have an
      adverse effect on the growth of California red kidney bean (Phaseolus vulgaris)
      and rye grass (Lolium perenne) plants in the concentration range tested.
      California red beans did not show uptake of aluminum, while the situation was
      different for rye grass where a 2.5-fold increase in Al concentration in the
      leaves was observed as compared with control tests. Nano-aluminum particles in
      suspension do not appear to have an impact on the metabolic activity of Vibrio
      fischeri. However, when the nano-aluminum particles were amended to the soil,
      Alex aluminum resulted in a 50% reduction of light output at concentrations below
      5000 mg/L soil suspension concentration while L-Alex showed a similar effect at
      around 17,500 mg/L and the control soil at 37,500 mg/L. Soil respiration studies
      show that there are not statistical differences between the time and sizes of
      peaks in CO(2) production and the total mineralization of glucose.

PMID- 17537427
TI  - Effect of beta-adrenoceptors on the behaviour induced by the neuropeptide
      glutamic acid isoleucine amide.
AB  - Excessive grooming behaviour is induced by intracerebroventricular injections of
      the neuropeptide glutamic acid isoleucine amide (neuropeptide-EI), via the
      activation of A-10 dopaminergic neurons and the noradrenergic system. Our object
      was to study the latter system involved in these behaviours, using male Wistar
      rats weighing 250-300 g with i.c.v. implants. The results show that all the
      adrenoceptor antagonists "per se" do not affect excessive grooming behaviour or
      motor activity. Intracerebroventricular administration of propranolol, a general
      beta-adrenoceptor antagonist, before neuropeptide-EI, inhibited the induced
      excessive grooming behaviour in a dose dependent manner. Metoprolol, a beta(1)
      adrenoceptor antagonist, also blocked this behaviour. However,
      intracerebroventricular injections of phentolamine, an alpha-adrenoceptor
      antagonist, and ((+/-)-1-[2,3-(Dihydro-7-methyl-1H-inden-4-yl)oxy]-3-[(1
      methylethyl)amino]-2-butanol), a beta(2)-adrenoceptor antagonist, had no effect
      on the behaviour induced by neuropeptide-EI induced behaviour for any of the
      doses tested. On the other hand, isoproterenol, a general beta-adrenoceptor
      agonist and dobutamine, a beta(1)-adrenoceptor agonist, both elicited similar
      behaviours as those induced by neuropeptide-EI. These results support the
      hypothesis that a relationship exists between neuropeptide-EI and beta
      adrenoceptors, more specifically the beta(1)-adrenoceptor, as found with other
      similar endogenous peptides such as neurotensin, cholecystin, substance P and
      alpha-melanocyte stimulating hormone. Hence, neuropeptide-EI could probably be
      exerting a neuromodulating effect on the central nervous system.

PMID- 17537428
TI  - Tanshinone IIA protects cardiac myocytes against oxidative stress-triggered
      damage and apoptosis.
AB  - Tanshinone IIA (tan), a derivative of phenanthrenequinone, is one of the key
      components of Salvia miltiorrhiza Bunge. Previous reports showed that tan
      inhibited the apoptosis of cultured PC12 cells induced by serum withdrawal or
      ethanol. However, whether tan has a cardioprotective effect against apoptosis
      remains unknown. In this study, we investigated the effects of tan on cardiac
      myocyte apoptosis induced both by in vitro incubation of neonatal rat ventricular
      myocytes with H(2)O(2) and by in vivo occlusion followed by reperfusion of the
      left anterior descending coronary artery in adult rats. In vitro, as revealed by
      3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium (MTT) assay, treatment with
      tan prior to H(2)O(2) exposure significantly increased cell viability. Tan also
      markedly inhibited H(2)O(2)-induced cardiomyocyte apoptosis, as detected by
      ladder-pattern fragmentation of genomic DNA, chromatin condensation, and
      hypodioloid DNA content. In vivo, tan significantly inhibited
      ischemia/reperfusion-induced cardiomyocyte apoptosis by attenuating morphological
      changes and reducing the percentage of terminal transferase dUTP nick end
      labeling (TUNEL)-positive myocytes and caspase-3 cleavage. These effects of tan
      were associated with an increased ratio of Bcl-2 to Bax protein in
      cardiomyocytes, an elevation of serum superoxide dismutase (SOD) activity and a
      decrease in serum malondialdehyde (MDA) level. Taken together, these data for the
      first time provide convincing evidence that tan protects cardiac myocytes against
      oxidative stress-induced apoptosis. The in vivo protection is mediated by
      increased scavenging of oxygen free radicals, prevention of lipid peroxidation
      and upregulation of the Bcl-2/Bax ratio.

PMID- 17537429
TI  - Participation of glucose transporters on atrial natriuretic peptide-induced
      glucose uptake by adult and neonatal cardiomyocytes under oxygenation and
      hypoxia.
AB  - Natriuretic peptides, beside their endocrine actions, have paracrine functions
      which include regulating glucose uptake and metabolism. Atrial natriuretic
      peptide (ANP) actions are mediated by cGMP which is implicated in the metabolic
      adaptation of glucose metabolism to oxygen deprivation in the heart. Although, it
      has been reported that ANP increases glucose uptake, cGMP decreases it. The aim
      of the present paper was to evaluate the role of the glucose transporters 1 and 4
      (GLUTS), in glucose uptake produced by ANP in fatty acid-dependent adult
      cardiomyocytes and glucose-dependent neonatal cardiomyocytes under oxygenation
      and hypoxia, which reverts adult metabolism to glucose-dependent. We also
      explored if the calcium-calmodulin complex participates in ANP-induced increase
      in glucose uptake. Neonatal cells had a higher glucose uptake than adult cells
      and GLUT 1 participated in basal uptake in both cell types. Hypoxia increased
      glucose uptake in adult cardiomyocytes but not in neonatal cells and this
      increase in glucose uptake was mediated by GLUT4. ANP increased glucose uptake in
      both adult and neonatal myocytes, under oxygenation and hypoxia, and GLUT4
      favored this increase. Neonatal cells were less sensitive to ANP.
      Trifluoperazine, a calcium-calmodulin blocker, inhibited the ANP-induced increase
      in glucose uptake. This suggests that ANP promotes GLUT 4 calcium-mediated
      recruitment to the cell membrane. In conclusion, glucose uptake regulation is one
      of the paracrine metabolic effects of ANP in adult and neonatal cardiomyocytes
      under oxygenation and hypoxia. This effect of this peptide could explain the
      beneficial effects found in the internal medicine and surgical fields.

PMID- 17537430
TI  - Role of ERK1/2 signaling pathways in 4-aminopyridine-induced rat pulmonary
      vasoconstriction.
AB  - The aim of the present study was to investigate the contribution of extracellular
      signal regulated kinase-1/2 (ERK1/2) to pulmonary artery contraction in response
      to 4-aminopyridione (4-AP), an inhibitor of a voltage-gated K(+) channels that
      regulate pulmonary vascular tone. Pulmonary artery rings 1-1.5 mm in diameter
      from male adult Wistar rat were isolated and cut into 3-mm in length. ERK1/2 up
      stream kinase (MEK) inhibitors 2'-amino-3'-methoxyflavone (PD98059) and 1,4
      diamino-2,3-dicyano-1,4-bis (2-aminophenylthio)-butadiene (U0126), which block
      the activation of ERK1/2, were used to test the role of ERK1/2 in 4-AP induced
      pulmonary arterial vasoconstriction and the influences of 4-AP on expressions of
      phosphorylated ERK1/2 (p-ERK1/2) in cultured rat pulmonary arterial smooth muscle
      cells (PASMCs) and whole tissues. Our results show that 4-AP elicited
      concentration-dependent increases in tension of rat pulmonary artery rings,
      effects that were reduced by pretreatment of the rings with ERK inhibitors,
      PD98059 (20 microM) and U0126 (10 microM). Moreover, 4-AP increased the
      expressions of p-ERK1/2 in cultured PASMCs s and whole tissues, which were
      prevented by pretreatment of the cells or tissues with U0126. These results
      indicate that ERK1/2 signaling pathway contributes to pulmonary vasoconstriction
      induced by 4-AP.

PMID- 17537431
TI  - The human histamine H3 receptor couples to GIRK channels in Xenopus oocytes.
AB  - The histamine H(3) receptor mediates inhibitory responses in the nervous system.
      Here, we demonstrate the coupling of the human histamine H(3) receptor to G
      protein-coupled inward rectifier potassium (GIRK) channels in Xenopus oocytes,
      using voltage-clamp. The histamine H(3) receptor agonist (R)-alpha
      methylhistamine increased GIRK currents with an EC(50) of 2.5 nM. The response to
      (R)-alpha-methylhistamine was inhibited by the specific antagonist/inverse
      agonist clobenpropit. GIRK channels represent a novel effector pathway for the
      histamine H(3) receptor, also suggesting the use of electrophysiology assays in
      histamine H(3) receptor drug screening, allowing for the resolution of G protein
      activation kinetics.

PMID- 17537432
TI  - Stress-induced hyperthermia: effects of acute and repeated dosing of MPEP.
AB  - The mGlu5 receptor antagonist 2-methyl-6-(phenylethylnyl)-pyridine (MPEP) is
      highly anxiolytic in rodent models of anxiety. Recent studies showed that MPEP
      remains effective in some models of anxiety after repeated treatment, but
      tolerance may develop in other models. To further evaluate anxiolytic properties
      of repeated MPEP, a single administration of 3, 10, or 30 mg/kg p.o. and repeated
      administration of 30 mg/kg p.o. was tested in the stress-induced hyperthermia
      model in mice. MPEP dose-dependently inhibited stress-induced hyperthermia when
      given acutely. MPEP remained equally active in reducing stress-induced
      hyperthermia after five daily treatments with 30 mg/kg, further validating MPEP
      as a potential anxiolytic for chronic use.

PMID- 17537433
TI  - Galectin-1, an endogenous lectin produced by arterial cells, binds lipoprotein(a)
      [Lp(a)] in situ: relevance to atherogenesis.
AB  - Lipoprotein(a) [Lp(a)], a modified LDL molecule, is implicated in atherogenesis.
      Mechanisms of the accumulation of [Lp(a)] in atherosclerotic vessels is lacking
      in literature. We sought to investigate the complementarities of the carbohydrate
      structures on Lp(a) and LDL with galectin-1(a carbohydrate binding protein) and
      whether endogenous galectin-1 binds Lp(a) in situ. We investigated T-antigen
      structures on Lp(a) and LDL by enzyme-linked lectin assay using T-antigen
      specific lectins, galectin-1 and jacalin. Both jacalin and galectin-1 bound
      strongly to Lp(a) and to a much lesser extent, to LDL. Galectin-1 recognition of
      the lipoproteins was abolished when the O-linked sugars were selectively removed.
      Localization of endogenous galectin-1 within histological sections of human
      internal mammary artery and in vitro binding of Lp(a) to the tissues was analyzed
      by immunohistochemical staining. The Lp(a)-binding pattern was found to overlap
      with the localization of galectin-1. The poor Lp(a)-binding on inhibiting tissue
      galectin-1 with lactose, suggested the binding of Lp(a) to galectin-1. This may
      be suggestive of a mechanism by which Lp(a) accumulates within arterial walls in
      atherogenesis.

PMID- 17537434
TI  - Palladin interacts with SH3 domains of SPIN90 and Src and is required for Src
      induced cytoskeletal remodeling.
AB  - Palladin and SPIN90 are widely expressed proteins, which participate in
      modulation of actin cytoskeleton by binding to a variety of scaffold and
      signaling molecules. Cytoskeletal reorganization can be induced by activation of
      signaling pathways, including the PDGF receptor and Src tyrosine kinase pathways.
      In this study we have analyzed the interplay between palladin, SPIN90 and Src and
      characterized the role of palladin and SPIN90 in PDGF and Src-induced
      cytoskeletal remodeling. We show that the SH3 domains of SPIN90 and Src directly
      bind palladin's poly-proline sequence and the interaction controls intracellular
      targeting of SPIN90. In PDGF-treated cells, palladin and SPIN90 co-localize in
      actin-rich membrane ruffles and lamellipodia. The effect of PDGF on the
      cytoskeleton is at least partly mediated by the Src kinase since PP2, a selective
      Src kinase family inhibitor, blocked PDGF-induced changes. Furthermore,
      expression of active Src kinase resulted in coordinated translocation of both
      palladin and SPIN90 to membrane protrusions. Knock-down of endogenous SPIN90 did
      not inhibit Src-induced cytoskeletal rearrangement, whereas knock-down of
      palladin resulted in cytoskeletal disorganization and inhibition of remodeling.
      Further studies showed that palladin is tyrosine phosphorylated in cells
      expressing active Src indicating bidirectional interplay between palladin and
      Src. These results may have implications in understanding the invasive and
      metastatic phenotype of neoplastic cells induced by Src.

PMID- 17537435
TI  - Rapid trafficking of c-Src, a non-palmitoylated Src-family kinase, between the
      plasma membrane and late endosomes/lysosomes.
AB  - Src-family kinases (SFKs) are co-expressed with multiple combinations of each
      member in a single cell and involved in various signalings. Recently, we showed
      by sucrose-density gradient fractionation that the subcellular distribution of c
      Src is distinct from that of Lyn. However, little is known about the trafficking
      of c-Src in living cells. Here, we show by time-lapse monitoring combined with
      photobleaching techniques that c-Src, a non-palmitoylated SFK, is rapidly
      exchanged between the plasma membrane and intracellular organelles representing
      late endosomes/lysosomes possibly through its cytosolic release. Although Lyn, a
      palmitoylated SFK, is exocytosed to the plasma membrane via the Golgi apparatus
      along the secretory pathway, lack of palmitoylation directs Lyn away from the
      exocytotic transport to the c-Src-type trafficking between the plasma membrane
      and late endosomes/lysosomes. Intriguingly, c-Src and a non-palmitoylated Lyn
      mutant are efficiently delivered and immobilized to focal adhesions when their
      SH2 domains are able to mediate protein-protein interactions in place of
      intramolecular bindings. However, palmitoylation of Lyn inhibits its recruitment
      to focal adhesions. These results suggest that palmitoylation of SFKs is critical
      for SFK localization and trafficking and implicate that two distinct trafficking
      pathways for SFKs may be involved in SFKs' specific functions.

PMID- 17537436
TI  - Differential regulation of parvocellular neuronal activity in the paraventricular
      nucleus of the hypothalamus following single vs. repeated episodes of water
      restriction-induced drinking.
AB  - Acute activation of the hypothalamic-pituitary-adrenal (HPA) axis releases
      glucocorticoids to maintain homeostasis, whereas prolonged exposure to elevated
      glucocorticoids has deleterious effects. Due to the potential benefits of
      limiting stress-induced glucocorticoid secretion, the present study uses drinking
      in dehydrated rats as a model to delineate mechanisms mobilized to rapidly
      inhibit HPA activity during stress. Using Fos expression as an indicator of
      neuronal activation, the effect of a single or repeated episode of dehydration
      induced drinking on the activity of magnocellular and parvocellular neurons in
      the paraventricular nucleus (PVN) of the hypothalamus was examined. Adult male
      rats underwent a single episode or repeated (six) episodes of water restriction
      and were sacrificed before or after drinking water in the AM. Plasma osmolality,
      vasopressin (AVP), adrenocorticotropic hormone (ACTH) and corticosterone were
      elevated by water restriction and reduced after drinking in both models. Fos
      expression was elevated in AVP-positive magnocellular PVN neurons and AVP- and
      corticotropin releasing hormone (CRH)-positive parvocellular PVN neurons after
      water restriction. Fos expression was reduced in magnocellular AVP neurons after
      both models of restriction-induced drinking. In contrast, Fos expression did not
      change in AVP and CRH parvocellular neurons after a single episode of restriction
      induced drinking, but was reduced after repeated episodes of restriction-induced
      drinking. These data indicate that drinking-induced decreases in glucocorticoids
      in dehydrated rats involve multiple factors including reduction in magnocellular
      release of vasopressin and reduction in parvocellular neuronal activity. The
      differential inhibition of PVN parvocellular neurons after repeated rehydration
      may reflect a conditioned response to repeated stress reduction.

PMID- 17537437
TI  - Computational study of bindings of olive leaf extract (OLE) to HIV-1 fusion
      protein gp41.
AB  - Recent experimental study found that OLE (olive leaf extract) has anti-HIV
      activity by blocking the HIV virus entry to host cells [Lee-Huang, S., Zhang, L.,
      Huang, P.L., Chang, Y. and Huang, P.L. (2003) Anti-HIV activity of olive leaf
      extract (OLE) and modulation of host cell gene expression by HIV-1 infection and
      OLE treatment. Biochem. Biophys. Res. Commun. 307, 1029; Lee-Huang, S., Huang,
      P.L., Zhang, D., Lee, J.W., Bao, J., Sun, Y., Chang, Y.-Tae, Zhang, J.Z.H. and
      Huang, P.L. (2007) Discovery of small-molecule HIV-1 fusion and integrase
      inhibitors oleuropein and hydroxytyrosol. Biochem. Biophys. Res. Commun. 354, 872
      878, 879-884]. As part of a joint experimental and theoretical effort, we report
      here computational study to help identify and characterize the binding complexes
      of several main compounds of OLE (olive leaf extract) to HIV-1 envelop protein
      gp41. A number of possible binding modes are found by docking oleuropein and its
      metabolites, aglycone, elenolic acid and hydroxytyrosol, onto the hydrophobic
      pocket on gp41. Detailed OLE-gp41 binding interactions and free energies of
      binding are obtained through molecular dynamics simulation and MM-PBSA
      calculation. Specific molecular interactions in our predicted OLE/gp41 complexes
      are identified and hydroxytyrosol is identified to be the main moiety for binding
      to gp41. This computational study complements the corresponding experimental
      investigation and helps establish a good starting point for further refinement of
      OLE-based gp41 inhibitors.

PMID- 17537439
TI  - Paradox of epithelial cell calcium homeostasis during vectorial transfer in
      crayfish kidney.
AB  - The molting cycle of the freshwater crayfish, Procambarus clarkii, has been used
      as a model to study the cellular physiology and molecular biology of Ca "supply"
      proteins that effect transcellular vectorial Ca(2+) movement to achieve
      organismal Ca homeostasis. Specifically, periods of net Ca(2+) influx (postmolt)
      have been compared with periods of net Ca(2+) balance (intermolt). The broader
      goal is to understand the paradox facing epithelial cells of maintaining low
      cytosolic Ca(2+)in the face of mass Ca(2+)transit across epithelial cells. This
      mini-review compares mRNA and protein expression profiles for a series of
      proteins that are of strategic importance in effecting transcellular Ca(2+) flux
      in a selected epithelium, the antennal gland (kidney analog) specifically during
      apical to basolateral Ca(2+) conveyance. Target proteins were selected as
      representative of key "stages" in the transcellular transfer of Ca(2+): import
      (epithelial Ca(2+) channel, ECaC); storage (sarco/endoplasmic reticulum Ca(2+)
      ATPase, SERCA); buffering (sarcoplasmic Ca(2+) binding protein, SCP); and export
      (plasma membrane Ca(2+) ATPase, PMCA and Na(+)/Ca(2+) exchanger, NCX). The
      purpose of this review is to assess coordination of expression of these target
      proteins at times of high Ca(2+) demand (premolt and postmolt) compared to low Ca
      demand (intermolt) as a function of cellular location (apical vs. basolateral;
      endomembranes vs. plasma membranes) and relative abundance within different
      regions of the antennal gland. Understanding the spatiotemporal regulation of
      Ca(2+) handling proteins involved in transcellular transport is fundamental to
      investigating their endocrine regulation.

PMID- 17537438
TI  - Phylogenetic analysis of the insulin-like growth factor binding protein (IGFBP)
      and IGFBP-related protein gene families.
AB  - Insulin-like growth factor (IGF) activity is regulated by six high affinity
      binding proteins (IGFBPs) and possibly by some of the nine IGFBP-related proteins
      (IGFBP-rPs). To determine the phylogenetic relationship of this proposed gene
      superfamily, we conducted maximum likelihood (ML) and Bayesian inference analyses
      on a matrix of amino acid sequences from a diversity of vertebrate species. A
      single most likely phylogram, ML bootstrap, and Bayesian consensus tree of
      10,000,000 generations revealed a monophyletic IGFBP lineage independent of the
      IGFBP-rPs. The IGFBPs segregated into three distinct clades: IGFBP-1, -3, and -6.
      Subsequent gene duplication events within the IGFBP-1 and -3 clades resulted in
      the production and divergence of IGFBP-2 and -4 within the IGFBP-1 clade and
      IGFBP-5 in the IGFBP-3 clade. By contrast, the IGFBP-rPs were distributed
      paraphyletically into two clades: IGFBP-rP1, 5, and 6 in one clade and the CCN
      family (IGFBP-rP2-4,7-9) in another. A recently identified IGFBP-3 homolog in
      rainbow trout localized to the IGFBP-2 subclade. Subsequence analysis identified
      a RGD motif common to IGFBP-2 orthologs, but did not identify the nuclear
      localization sequence present in IGFBP-3 and -5 homologs. The putative trout
      IGFBP-3 was 36-55% identical to different IGFBP-2 proteins, but only 24-27%
      identical to IGFBP-3 proteins. These results suggest that the IGFBPs and IGFBP
      rPs are at best distantly related and that the limited similarities likely
      resulted from exon shuffling. They also suggest that rainbow trout, and possibly
      other salmonids, possess two IGFBP-2 paralogs as the putative trout IGFBP-3 is
      misannotated.

PMID- 17537440
TI  - Transabdominal and transvaginal ultrasonography of placenta previa.

PMID- 17537441
TI  - Thalassemia intermedia, inherited thrombophilia, and intrauterine growth
      restriction.

PMID- 17537442
TI  - Experimental evidence for a hierarchy of mate- and host-induced cues in a fish
      ectoparasite, Argulus coregoni (Crustacea: Branchiura).
AB  - Argulus coregoni is an ectoparasite primarily infesting freshwater salmonids.
      Sexually reproducing parasites such as A. coregoni are confronted with a dilemma
      between finding a mate and the costs involved in doing so; if mating partners are
      unavailable on a host, by leaving to search for a mate on a new host, the
      parasite is exposed to risks such as predation and energy loss. The utilization
      of chemical cues could enhance the probability of finding a host and/or a
      suitable mating partner and thus decrease the level of costs associated with
      detachment from the host. In this study we constructed a Y-maze arena to
      determine if adult A. coregoni respond to mate- and host-related chemical cues.
      We also tested the directional response towards light, since it has been
      suggested that photic cues are the most important cues for juvenile A. coregoni
      locating a host. Our results showed that both sexes were attracted to light and
      fish odour. Free-swimming A. coregoni males responded to chemical cues produced
      by adult females but not vice versa. The hierarchy of these stimuli was analyzed
      by pitting the cues against one another in the Y-maze, showing that light was the
      most salient stimulus for both male and female parasites. Moreover, male
      parasites were more strongly attracted towards light and fish odour than female
      odour. In another experiment in a semi-natural environment, we examined whether
      the ability of A. coregoni males to detect female odour influences their host
      choice. Free-swimming males did not preferentially infest fish infected with
      female parasites over parasite-free fish. We suggest that a hierarchy of stimulus
      responses exists, whereby free-swimming parasites first respond to host-related
      signals and most dominantly to visual cues. However, cues connected to mate
      finding may become a priority for late adult stages and/or once the parasite has
      attached to the host.

PMID- 17537443
TI  - Cellular interactions of Plasmodium liver stage with its host mammalian cell.
AB  - The Plasmodium liver forms are bridgehead stages between the mosquito sporozoite
      stages and mammalian blood stages that instigate the malaria disease. In
      hepatocytes, Plasmodium achieves one of the fastest growth rates among eukaryotic
      cells. However, nothing is known about host hepatic cell interactions, e.g.
      nutrient scavenging and/or subversion of cellular functions necessary for
      Plasmodium development and replication. Plasmodium usually invades hepatocytes by
      establishing a parasitophorous vacuole wherein it undergoes multiple nuclear
      division cycles. We show that Plasmodium preferentially develops in the host
      juxtanuclear region. By comparison with the parasitophorous vacuole of other
      apicomplexan parasites which associate with diverse host organelles, the
      Plasmodium parasitophorous vacuole only forms an association with the host
      endoplasmic reticulum. Intrahepatic Plasmodium actively modifies the permeability
      of its vacuole to allow the transfer of a large variety of molecules from the
      host cytosol to the vacuolar space through open channels. In contrast with
      malaria blood stages, the pores within the parasitophorous vacuole membrane of
      the liver stage display a smaller size as they restrict the passage of solutes to
      less than 855Da. These pores are stably maintained during parasite karyokinesis
      until complete cellularisation. Host-derived cholesterol accumulated at the
      parasitophorous vacuole membrane may modulate the channel activity. These
      observations define the parasitophorous vacuole of the Plasmodium liver stage as
      a dynamic and highly permeable compartment that can ensure the sustained supply
      of host molecules to support parasite growth in the nutrient-rich environment of
      liver cells.

PMID- 17537444
TI  - Association of paraoxonase activity and coronary blood flow.
AB  - BACKGROUND: Paraoxonase (PON) is a high-density lipoprotein-bound anti-oxidant
      enzyme that inhibits atherosclerosis and endothelial dysfunction. Slow coronary
      flow (SCF) has long been identified and endothelial dysfunction and
      atherosclerosis of epicardial coronary arteries and microvasculature were
      reported to be associated with SCF. Consequently, we aimed to investigate the
      association between coronary blood flow by means of Thrombolysis in Myocardial
      Infarction frame count (TFC) and serum PON activity and other laboratory
      parameters in patients with SCF compared to control cases. METHODS: Twenty-four
      patients with SCF and 110 control cases with normal coronary flow were studied
      after quantifying coronary blood flow according to TFC. Serum PON activity was
      evaluated by measuring the rate of paraoxon hydrolysis. The association between
      TFC and serum PON activity and other clinical and laboratory parameters were
      evaluated. RESULTS: There were statistically significant differences between SCF
      and control groups in respect to serum uric acid (p=0.001), high sensitive C
      reactive protein (p=0.03) levels and serum PON activity (p<0.001). The mean TFC
      was correlated with male gender (r=0.263, p=0.002), serum uric acid level
      (r=0.287, p=0.001), hemoglobin concentration (r=0.192, p=0.032) and serum PON
      activity (r=-0.306, p<0.001). Serum uric acid level (chi(2)=10.08, beta=0.362,
      p=0.009) and serum PON activity (chi(2)=16.73, beta=-0.005, p=0.001) were
      independent predictors of SCF whereas the only independent predictor of mean TFC
      was serum PON activity (beta=-0.318, p<0.001). CONCLUSION: These findings suggest
      that serum PON activity is independently associated with mean TFC and reduced
      serum PON activity might represent a biochemical marker of SCF.

PMID- 17537445
TI  - Molecular weight and structure characterization of sodium hyaluronate and its
      gamma radiation degradation products by flow field-flow fractionation and on-line
      multiangle light scattering.
AB  - A combined flow field-flow fractionation (FlFFF)/multiangle light scattering
      (MALS)/differential refractive index (DRI) detection method has been utilized for
      the size fractionation and characterization of ultrahigh molecular weight (MW)
      sodium hyaluronate (NaHA) samples. Separation of broad MW NaHA polymers was
      carried out by a frit inlet asymmetrical FlFFF channel employed with a linear
      field programming method followed by the on-line monitoring of light scattering
      at multiple angles for the calculation of MW and for the study of the
      conformation of NaHA samples. NaHA samples examined were: (1) two different
      viscosity fractions of NaHA obtained by a refinement process and (2) NaHA
      products of gamma radiation degradation. While the NaHA samples of two different
      viscosity fractions exhibited clearly different MW distributions and similar
      conformation, the radiation degraded NaHA samples showed a clear difference in
      both MW distribution and polymer structure.

PMID- 17537446
TI  - Selective enrichment of ochratoxin A using human serum albumin bound magnetic
      beads as the concentrating probes for capillary electrophoresis/electrospray
      ionization-mass spectrometric analysis.
AB  - Ochratoxin A (OTA) is a toxicant commonly present in many food products.
      Conventionally, immuno-affinity analysis is applied to rapidly screen the
      presence of OTA in food. However, antibodies are expensive. In this study, we
      present a new approach for selectively enriching OTA from aqueous samples using
      human serum albumin (HSA) bound magnetic beads as the affinity probes, followed
      by the analysis of CE/ESI-MS. In addition to demonstrating the feasibility of
      using the affinity probes to concentrate OTA, we also propose a rapid
      concentration and elution method for extraction, that is, OTA are extracted from
      aqueous samples by pipetting the samples in and out of a sample vial for 1 min
      followed by elution with pipetting for another minute. On the basis of the
      magnetic property, the affinity magnetic probe-target species could be rapidly
      isolated from the solution during the process of extraction and elution by
      magnetic separation. CE/ESI-MS, coupled by the electrodeless/sheathless
      interface, is used for the analysis of the samples. As this method features speed
      and cost-effectiveness, it is suitable for the purpose of rapid screening. In
      fact, the lowest detection limit for OTA is approximately 4 x 10(-3) mg/L.

PMID- 17537447
TI  - Influence of the hydrothermal treatment on the chromatographic properties of
      monolithic silica capillaries for nano-liquid chromatography or capillary
      electrochromatography.
AB  - In the last decade, silica monolithic capillaries have focused more and more
      attention on miniaturized separation techniques like capillary
      electrochromatography (CEC), nano-liquid chromatography (nano-LC) and chip
      electrochromatography owing to their unique chromatographic properties and their
      simplified preparation compared with packed columns. They are synthesized
      according to a sol-gel multi-step process that includes, after a gelation step at
      40 degrees C leading to the formation of the macropores network and the silica
      skeleton, a post-gelation step (hydrothermal treatment at 120 degrees C in basic
      medium) that allows to tailor the mesopores and finally a calcination or a
      washing step to remove remaining polymers. In order to reduce the synthesis time,
      the number of synthesis steps and above all the temperature synthesis, to adapt
      the synthesis of such silica monoliths in polymeric microsystem devices, we
      extensively studied the influence of the hydrothermal treatment and its duration
      on textural (pore size distribution) and chromatographic properties (retention,
      efficiency) of in situ-synthesized capillary monoliths in nano-LC and CEC. This
      study was performed on pure silica and octyl chains grafted silica monoliths.
      Untreated monoliths show small pores (<6 nm), whereas hydrothermally treated
      monoliths exhibit medium and large mesopores (8-17 nm). It was demonstrated that
      the hydrothermal treatment at 120 degrees C was not necessary for pure silica
      monolithic capillaries dedicated to normal phase liquid chromatography or
      hydrophilic interaction liquid chromatography (HILIC) and electrochromatography:
      the suppression of the hydrothermal treatment did not impair efficiencies in CEC
      and in nano-LC but contributed to increase in retention factors. Minimal plate
      heights of ca. 5 microm in CEC and 6 microm in nano-LC were obtained with or
      without hydrothermal treatment with bare silica. In the same way, the
      hydrothermal treatment was not necessary for grafted silica monoliths only
      dedicated to CEC. However, the results clearly indicate that the hydrothermal
      treatment becomes essential before grafting in order to preserve the efficiency
      of the monolithic silica capillaries dedicated to nano-LC: in this particular
      case, the suppression of the hydrothermal treatment leads approximately to a loss
      of a factor two in efficiency.

PMID- 17537448
TI  - Evaluation of multi-modal high salt binding ion exchange materials.
AB  - The performance and selectivity of novel cation and anion exchange multi-modal
      chromatographic materials were evaluated. Desorption profiles of 13 proteins
      possessing a range of properties (e.g. size, charge and hydrophobicity) were
      determined on the cation exchange materials. Batch experiments were carried out
      by loading individual proteins on each resin at low salt, and examining the
      desorption of the proteins during sequential washes with increasing salt
      concentrations. While all of the resins exhibited some binding of proteins at
      elevated salt concentrations, this effect was more pronounced on the resins with
      aromatic ligands as compared to the materials with aliphatic ligands. As
      expected, materials with higher ionic capacities exhibited higher binding at
      elevated salts. In addition, some proteins exhibited high binding at elevated
      salt concentrations to all of the resins. The combined effect of charge and other
      secondary interactions with these multi-modal chromatographic materials enables
      high salt binding of a range of proteins as well as unique selectivities for the
      recovery of certain classes of proteins. Since the anion exchange materials all
      exhibited high binding at elevated salt concentrations the work with these
      materials focused on a study of elution strategies to remove proteins from these
      aromatic based materials. After evaluating various elution protocols, a combined
      strategy of pH change and chaotropic salt were shown to minimize electrostatic
      and hydrophobic interactions and was found to be an effective elution strategy
      for this class of anion exchange materials using peanut lectin as a model
      protein.

PMID- 17537449
TI  - Isothermal retention indices on poly(3,3,3-trifluoropropylmethylsiloxane)
      stationary phases.
AB  - Isothermal retention indices (I) of 56 solutes of varied chemical nature and
      polarity were determined by a well-proven accurate method on poly(3,3,3
      trifluoropropylmethylsiloxanes) with trifluoropropyl group percentages between 0
      and 50% within the 353-413 K temperature range. The column temperature effect on
      the retention index for a representative set of solutes was studied. The linear
      model and the recent expression I = a + bT(-1) + c ln T were discussed. The
      retention index dependence on the polymer polarity was also investigated.
      Principal component analysis and multiple linear regression (MLR) were applied to
      obtain retention models relating the I values to physicochemical and molecular
      properties of the solutes chromatographed. The best model of prediction of the
      retention in these fluorinated stationary phases was obtained by using the
      Abraham's descriptors.

PMID- 17537450
TI  - High-performance size-exclusion chromatography of humic substances on the
      hydroxyethyl methacrylate column.
AB  - HEMA, the copolymer of 2-hydroxyethyl methacrylate and ethylene dimethacrylate,
      has proven to be a suitable stationary phase for the size-exclusion
      chromatographic (SEC) characterization of humic substances in a wide pH range.
      The SEC measurements were performed typically with alkaline borate-based mobile
      phase: 0.025 mol/l Na2B4O7, 0.025 mol/l NaCl, 0.001 mol/l Na4P2O7, pH 9.1. After
      calibrating with globular protein standards, apparent molecular weights of
      typical peat- and coal-derived humic acids were estimated. The average molecular
      weights determined with the aid of the HEMA column were quite comparable with the
      values obtained previously by the method of low-pressure gel-permeation
      chromatography on the Sephadex column.

PMID- 17537451
TI  - Validation of a confirmatory method for the determination of macrolides in liver
      and kidney animal tissues in accordance with the European Union regulation
      2002/657/EC.
AB  - This study proposes a simple multiresidue liquid chromatography-diode array
      detector (LC-DAD) method capable of determining seven macrolide antibiotics in
      samples of liver and kidney animals at concentrations lower than those allowed by
      current legislation. Samples were prepared by homogenizing the tissue with EDTA
      McIlvaine's buffer and extracted with an Oasis HLB cartridge. The consumption of
      organic solvent during extraction was minimum. The analytes were detected by LC
      DAD and also by liquid chromatography-mass spectrometry with electrospray
      ionization (LC-(ESI)MS). The method was specific, stable and robust enough for
      the required purposes. The DAD method was validated in accordance with the
      European Commission Decision 657/2002. Recovery data were also satisfactory with
      values higher than 67% for most macrolide antibiotics extracted from liver and
      kidney samples spiked at 200 microg/kg, the lowest MRL established for the
      macrolides studied. The relative standard deviations (RSD (%), (n=3)) were lower
      than 13% and 15% for intra-day and inter-day assays. The method was applied to
      investigate the occurrence of the studied macrolides in 31 beef and kidney animal
      samples. The results obtained by LC-DAD for positive samples were compared to
      those obtained by LC-(ESI)MS. Therefore, the method with simpler instrumentation
      than a LC-(ESI)MS can be used as a control method and the results of the
      validation process demonstrate that this method is suitable for application in a
      European Union program for monitoring residues of veterinary drugs.

PMID- 17537452
TI  - Effective diffusion coefficient determination within cylindrical granules of
      adsorbents using a direct simulation method.
AB  - Analytical expressions for solute adsorption kinetics within porous carbon
      cylindrical granules of adsorbents with a one point formula for effective
      diffusion coefficient determination are available based on the assumption that
      solute transport is the rate limiting step and that it follows Fick's Second Law.
      Here the first practical application of this theory is provided with an initial,
      estimated diffusion coefficient refined by fitting calculated kinetic adsorption
      curves to experimental data determined for activated carbons. In an ideal
      experiment, experimental error (noise) is negligible, and no data refinement is
      needed. However, real experimental data are always more or less noise
      contaminated. Where such noise is significant, a simulation method offers the
      best value for effective diffusion coefficient. For this specific system, surface
      modification, pH and temperature effects on adsorption kinetics were analysed
      quantitatively as a basis of determining effective diffusion coefficients through
      the porous structure.

PMID- 17537453
TI  - Renal dysplasia unrelated to claudin-16 deficiency in Japanese Black cattle.
AB  - Renal lesions of the type usually found in claudin-16 (CL-16) defective Japanese
      Black cattle (homozygous for CL-16 deficiency) were identified in six animals of
      this breed, aged 28-59 months, which were either heterozygous for CL-16
      deficiency (type 1) or normal, as judged by a DNA-based test associated with the
      CL-16 gene. Histopathologically, all six cases showed elongated focal lesions
      which ran through the cortex to terminate in the outer zone of the medulla. The
      lesions contained components that included: (1) immature tubules, (2) small
      irregularly shaped tubules with thickening of the basement membrane, (3)
      mesenchymal cells in an increased interstitium, (4) small atrophic glomeruli, and
      (5) immature glomeruli. The glomeruli were noticeably reduced in number, and
      large glomeruli with an increased number of mesangial cells were observed
      throughout the entire cortical area. Cystic dilation of tubules and flattening of
      the epithelium were noted in all areas of the kidney. Histopathologically, the
      renal lesions in the six cases were indistinguishable from those reported
      previously in cattle homozygous for CL-16 deficiency. These findings demonstrate
      that such renal lesions in Japanese Black cattle are not necessarily associated
      with homozygous deletion of the CL-16 gene.

PMID- 17537454
TI  - Neoplastic and non-neoplastic cell lines from a malignant peripheral nerve sheath
      tumour of the cervix of a rat.
AB  - A homotransplantable tumour (LY) and cell lines (LY-PPB6 and LY-H12) were
      established from a spontaneous malignant peripheral nerve sheath tumour (PNST) of
      the uterine cervix of an F344 rat. Primary and LY tumours consisted of oval or
      spindle-shaped cells arranged in a flatfield or streaming fashion, and indistinct
      nuclear palisades were seen. Immunohistochemically, neoplastic cells reacted to
      vimentin, S-100 protein, neuron-specific enolase (NSE), myelin basic protein
      (MBP), and glial fibrillary acidic protein (GFAP) in varying degrees, indicating
      neurogenic derivation. LY-PPB6-induced tumours in syngeneic rats developed
      cellular whorling patterns reacting particularly strongly to S-100 protein, NSE,
      MBP and GFAP. Nerve growth factor (NGF) mRNA expression was shown in LY-PPB6
      cells by the reverse transcription-polymerase chain reaction (RT-PCR). By
      contrast, LY-H12 had a normal chromosomal number of 42, and did not produce
      tumours when injected into syngeneic rats. LY-H12 cells reacted to vimentin and
      alpha-smooth muscle actin (alpha-SMA), and the alpha-SMA-positive cell number was
      increased dose-dependently by the addition of transforming growth factor (TGF)
      beta1, indicating a myofibroblastic nature. LY-PPB6 cells were neoplastic with
      properties of PNS cells, whereas LY-H12 cells were non-neoplastic stromal cells
      showing myofibroblastic differentiation. As TGF-beta1 mRNA expression was shown
      in both LY-PPB6 and LY-H12 cells by the RT-PCR, the myofibroblastic phenotype of
      LY-H12 cells may be mediated by paracrine or autocrine signalling in tumour
      tissues. LY-PPB6 and LY-H12 may prove useful for studies on the pathobiological
      nature of neoplastic cells and interactions between neoplastic and stromal cells
      in PNSTs.

PMID- 17537455
TI  - Induction of actin gene expression in the mosquito midgut by blood ingestion
      correlates with striking changes of cell shape.
AB  - Ingestion of a blood meal by the female mosquito Anopheles gambiae (L., Diptera:
      Culicidae), results in a dramatic distention of the midgut epithelium. Here, we
      report that these events correlate with a transient increase of actin mRNA and
      protein abundance. The newly synthesized actin may provide a pool of actin
      protein needed to remodel epithelial cell cytoarchitecture. We also document
      changes in midgut epithelial cell morphology. Upon blood ingestion, the columnar
      cells flatten accompanied by the loss of microvilli on the lumenal side and the
      unfolding of the labyrinth on the basal side. These changes correlate with the
      large increase of epithelial surface area needed to accommodate the blood meal.
      Actin gene expression, actin synthesis and cell morphology all return to the pre
      feeding state by 24 h after blood intake.

PMID- 17537456
TI  - Structural insight into a molecular switch in tandem winged-helix motifs from
      elongation factor SelB.
AB  - Elongation factor SelB is responsible for co-translational incorporation of
      selenocysteine (Sec) into proteins. The UGA stop codon is recoded as a Sec codon
      in the presence of a downstream mRNA hairpin. In prokaryotes, in addition to the
      EF-Tu-like N-terminal domains, a C-terminal extension containing four tandem
      winged-helix motifs (WH1-4) recognizes the mRNA hairpin. The 2.3-A resolution
      crystal structure of the Escherichia coli WH3/4 domains bound to mRNA with
      mutagenesis data reveal that the two WH motifs use the same structural elements
      to bind RNA. The structure together with the 2.6-A resolution structure of the
      WH1-4 domains from Moorella thermoacetica bound to RNA revealed that a salt
      bridge connecting WH2 to WH3 modules is disrupted upon mRNA binding. The results
      provide a structural basis for the molecular switch that may allow communication
      between tRNA and mRNA binding sites and illustrate how RNA acts as an activator
      of the switch. The structures show that tandem WH motifs not only provide an
      excellent scaffold for RNA binding but can also have an active role in the
      function of protein-RNA complexes.

PMID- 17537457
TI  - A comparison of functional outcomes in hypoxia and traumatic brain injury: a
      pilot study.
AB  - We present our experience with 30 patients on functional outcomes of patients
      with anoxic brain injury (ABI, n=15) due to cardiac etiologies from freestanding
      inpatient rehabilitation hospital. A convenience sample of patient with traumatic
      brain injury (TBI, n=15) with similar demographic characteristic to ABI was used
      for comparison on indices of activity of daily living, cognition, mobility as
      well as other indices of functional prognosis such as hospital length of stay,
      cost and discharge predisposition. No statistical significant differences were
      found between the two groups on the presently employed outcome measures. This
      investigation supports the positive impact of inpatient rehabilitation for
      individuals with hypoxia of cardiac etiology. Future research comparing outcomes
      of ABI to TBI with larger, controlled trials is warranted.

PMID- 17537458
TI  - Case of mononeuritis multiplex onset with rituximab therapy for Waldenstrom's
      macroglobulinemia.
AB  - Waldenstrom's macroglobulinemia (WM) is a lymphoplasmacytic disorder with
      associated monoclonal gammopathy. A wide variety of neuropathies can be
      associated with WM, but most commonly it is a mild length-dependent sensory
      neuropathy of unclear etiology. Rituximab is a monoclonal antibody which
      suppresses mature B-cell populations. It has increasingly been used in wide
      applications including WM, especially in those cases with severe neuropathy. The
      highlighted case provides an example of rituximab treatment complication in a WM
      patient with mild sensory neuropathy that evolved to multiple mononeuropathies
      with features of systemic vasculitis and unusual conversion of type I to type II
      cryoglobulinemia.

PMID- 17537459
TI  - Fever control and its impact on outcomes: what is the evidence?
AB  - Fever is common in a variety of neurological disorders. There is abundant
      experimental evidence suggesting that fever leads to, or exacerbates, neuronal
      injury in conditions such as cerebral ischemia and traumatic brain injury.
      However, conclusive evidence linking control of fever to improved outcomes is
      lacking. It has been difficult to design studies looking at the impact of fever
      control on outcome, in part because traditional methods of fever control are
      ineffective. Recently, several new devices to control temperature have become
      available. These devices appear to be more effective than conventional means and
      might allow us to design studies that definitively answer the question: "Does
      controlling fever improve outcome?"

PMID- 17537460
TI  - Monitoring brain tissue oxymetry: will it change management of critically ill
      neurologic patients?
AB  - Based on the assumption that brain ischemia and hypoxia are central causes of
      brain damage, the maintenance of an adequate tissue oxygenation is a primary
      objective in the field of neurocritical care. Thus, monitoring brain tissue
      oxymetry, allowing the possibility to discriminate between normal and critically
      impaired tissue oxygenation, is recognized as an essential part of the management
      of the neurological critically ill patient. The clinical usefulness of this
      neuromonitoring tool in the area of neurosciences (traumatic brain injury,
      aneurysm surgery, arteriovenous malformation resection, brain tumors) is
      discussed. Monitoring brain tissue oxymetry not only allows the detection of
      impending cerebral ischemia, thus providing the clinician with essential
      information for the management and correction of harmful intracerebral events,
      but it also helps in understanding the pathophysiology of neuro-injury. It can
      also be used as a "surrogate end point" to evaluate putative therapies, targeting
      therapy towards improved cerebral oxygenation. As brain tissue oxygenation
      correlates closely with outcome, several outcome categories have been
      differentiated, aiding in predicting prognosis after injury. The rationale for
      monitoring brain tissue oxygenation is to provide essential information about
      oxygen supply and utilization in this specific tissue bed, thus reducing
      secondary brain damage and improving neurological outcome.

PMID- 17537461
TI  - Induction of 5-aminolevulinate synthase by activators of steroid biosynthesis.
AB  - Different cytochromes P450 are involved in steroid biosynthesis. These
      cytochromes have heme as the prosthetic group. We previously reported that ACTH,
      an activator of glucocorticoid biosynthesis in adrenal, requires heme
      biosynthesis for a maximal response. In the present study, we investigated the
      effect of ACTH, and the effect of two activators of the adrenal mineralocorticoid
      synthesis, endothelin-1 and low sodium diet on 5-aminolevulinate-synthase (ALA-s)
      mRNA. ALA-s is the rate-limiting enzyme in heme biosynthesis. It was found that
      infusion of rats with ACTH for 1 h caused an increase of adrenal ALA-s mRNA and
      activity accompanied by an increase in plasma corticosterone. CYP21, a cytochrome
      involved in the synthesis of both corticosterone and aldosterone, was not
      modified at the RNA level in adrenal glands by 1 h of ACTH infusion.
      Consistently, infusion of endothelin-1 for 1 h increased ALA-s mRNA and
      aldosterone content in adrenal gland without modifying CYP21 mRNA levels. To
      study if ALA-s is also regulated by the main physiological stimuli that increase
      adrenal mineralocorticoid secretion, we fed rats with low salt diet for 2 or 15
      days. Low salt diet treatment increased adrenal gland ALA-s mRNA levels. On the
      other hand, the rapid stimulation of ALA-s mRNA by ACTH which acts through cyclic
      AMP was confirmed in H295R human adrenocortical cells, the only human adrenal
      cell line that has a steroid secretion pattern and regulation similar to primary
      cultures of adrenal cells. Our findings suggest that the acute activation of
      adrenal steroidogenic cytochromes by trophic hormones involves an increase in
      heme biosynthesis which will favor the production of active cytochromes.

PMID- 17537462
TI  - Low frequency and low intensity pulsed electromagnetic field exerts its
      antiinflammatory effect through restoration of plasma membrane calcium ATPase
      activity.
AB  - Rheumatoid arthritis (RA) is a chronic inflammatory disorder affecting 1% of the
      population worldwide. Pulsed electromagnetic field (PEMF) has a number of well
      documented physiological effects on cells and tissues including antiinflammatory
      effect. This study aims to explore the antiinflammatory effect of PEMF and its
      possible mechanism of action in amelioration of adjuvant induced arthritis (AIA).
      Arthritis was induced by a single intradermal injection of heat killed
      Mycobacterium tuberculosis at a concentration of 500 microg in 0.1 ml of paraffin
      oil into the right hind paw of rats. The arthritic animals showed a biphasic
      response regarding changes in the paw edema volume. During the chronic phase of
      the disease, arthritic animals showed an elevated level of lipid peroxides and
      depletion of antioxidant enzymes with significant radiological and histological
      changes. Besides, plasma membrane Ca(2+) ATPase (PMCA) activity was inhibited
      while intracellular Ca(2+) level as well as prostaglandin E(2) levels was noticed
      to be elevated in blood lymphocytes of arthritic rats. Exposure of arthritic rats
      to PEMF at 5 Hzx4 microT x 90 min, produced significant antiexudative effect
      resulting in the restoration of the altered parameters. The antiinflammatory
      effect could be partially mediated through the stabilizing action of PEMF on
      membranes as reflected by the restoration of PMCA and intracellular Ca(2+) levels
      in blood lymphocytes subsequently inhibiting PGE(2) biosynthesis. The results of
      this study indicated that PEMF could be developed as a potential therapy for RA
      in human beings.

PMID- 17537463
TI  - Remotely sensed assessment of water quality levels in the Pearl River Estuary,
      China.
AB  - In this paper, a method of assessing water quality from satellite data is
      introduced. The composite pollution index (CPI) was calculated from measured
      chemical oxygen demand (COD) and nutrient concentration. The relationships
      between CPI and 240 band combinations of SeaWiFS water-leaving radiance were
      analyzed and the optimal band combination for estimating CPI was chosen from the
      240 band combinations. An algorithm for retrieval of CPI was developed using the
      optimal band combination, (L(443)xL(510))/(L(412)+L(490)). The CPI was estimated
      from atmospherically corrected SeaWiFS data by employing the algorithm.
      Furthermore, the CPI value range for each water quality level was determined
      based on data obtained from 850 samples taken in the Pearl River Estuary. The
      remotely sensed CPIs were then transferred to water quality levels and
      appropriate maps were derived. The remotely sensed water quality level maps
      displayed a similar distribution of levels based on in situ investigation issued
      by the State Ocean Administration, China. This study demonstrates that remote
      sensing can play an important role in water quality assessment.

PMID- 17537464
TI  - Compartmental analysis in photophysics: kinetics and identifiability of models
      for quenching of fluorescent probes in micelles.
AB  - The parameters describing the kinetics of excited-state processes can possibly be
      recovered by analysis of the fluorescence decay surface measured as a function of
      the experimental variables. The identifiability analysis of a photophysical model
      assuming errorless time-resolved fluorescence data can verify whether the model
      parameters can be determined. In this work, we have used the methods of
      similarity transformation and Taylor series to investigate the identifiability of
      two models utilized to describe the time-resolved fluorescence quenching of
      stationary probes in micelles. The first model assumes that exchange of the
      quencher between micelles is much slower than the fluorescence decay of the
      unquenched probe (the 'immobile' quencher model). The second model assumes that
      quenchers exchange between the aqueous and micellar phases (the 'mobile' quencher
      model). For the 'immobile' quencher model, the rate constants for deactivation
      (k(0)) and quenching (k(q)) of the excited probe are uniquely identified together
      with the average number of quencher molecules per micelle. For the 'mobile'
      quencher model, the rate constants k(0) and k(q) are uniquely identified, as are
      the rate constants for entry (k(+)) and exit (k(-)) of one quencher molecule into
      and from a micelle, and the micellar aggregation number. The concomitant rate
      equations describing the time-resolved fluorescence are solved using z
      transforms.

PMID- 17537466
TI  - Stress and weight change in university students in the United Kingdom.
AB  - Students in the US have been shown to gain weight during their first year at
      university. This study examined whether students in Britain have a similar weight
      change during their first year at university, and tested the hypothesis that
      stress plays a role. A cross-sectional survey was conducted to assess stress and
      perceived weight change. Two hundred and sixty eight students at University
      College London completed the questionnaire at the end of their first year of
      university. On average, students reported a significant weight increase (1.53
      kg+/-2.70, p<0.001), although there was considerable variation, with 55% of the
      sample reporting weight gain, 12% weight loss, and 33% remaining stable. Logistic
      regression analyses demonstrated that stress was associated with greater risk of
      weight gain (OR, 1.27, 95% CI, 1.12 to 1.44, p=0.001) and weight loss (1.33, 1.10
      to 1.61, p=0.003), but associations were stronger among women. The associations
      remained unchanged after adjustment for health behaviours. Our findings confirm a
      modest weight gain over the first year at university, which was associated with
      higher levels of perceived stress in women.

PMID- 17537467
TI  - Anogenital distance predicts female choice and male potency in prairie voles.
AB  - Anogenital distance (AGD) in rodents is a useful indicator of masculinization or
      feminization due to prenatal hormonal effects. If such cues convey useful
      information about both 'maleness' and more importantly mate quality, then females
      may select males based on this cue or other cues related to it. We tested this
      hypothesis by asking if female prairie voles (Microtus ochrogaster) preferred
      males with relatively longer AGDs and if AGD correlated with fitness enhancing
      characteristics such as sperm count, sperm size, and gonad size. Not only did
      preferred males have significantly longer AGD and larger testes than nonpreferred
      males, but AGD was directly related to the testes size, seminal vesicle size, and
      the number of sperm stored. We re-evaluated data collected in semi-natural field
      enclosures and discovered that males that were members of a pairbond had longer
      AGD than single males. This later result, taken under semi-natural conditions,
      was consistent with results we obtained in the laboratory. Taken together these
      data indicate that AGD serves as a useful cue of male potency and that females
      preferentially associate with males that demonstrate this masculinized phenotype.
      Moreover, these data imply that females may select mates based on their potential
      to effectively fertilize ova, a potentially important trait for a species that
      forms life-long pairbonds.

PMID- 17537468
TI  - Factors contributing to enhanced freezing tolerance in wheat during frost
      hardening in the light.
AB  - The interaction between light and temperature during the development of freezing
      tolerance was studied in winter wheat (Triticum aestivum L. var. Mv Emese). Ten
      day-old plants were cold hardened at 5 degrees C for 12 days under normal (250
      micromol m(-2)s(-1)) or low light (20 micromol m(-2)s(-1)) conditions. Some of
      the plants were kept at 20/18 degrees C for 12 days at high light intensity (500
      micromol m(-2)s(-1)), which also increased the freezing tolerance of winter
      wheat. The freezing survival rate, the lipid composition, the antioxidant
      activity, and the salicylic acid content were investigated during frost
      hardening. The saturation level of hexadecanoic acid decreased not only in plants
      hardened at low temperature, but also, to a lesser extent, in plants kept under
      high light irradiation at normal growth temperature. The greatest induction of
      the enzymes glutathione reductase (EC 1.6.4.2.) and ascorbate peroxidase (EC
      1.11.1.11.) occurred when the cold treatment was carried out in normal light, but
      high light intensity at normal, non-hardening temperature also increased the
      activity of these enzymes. The catalase (EC 1.11.1.6.) activity was also higher
      in plants grown at high light intensity than in the controls. The greatest level
      of induction in the activity of the guaiacol peroxidase (EC 1.11.1.7.) enzyme
      occurred under cold conditions with low light. The bound ortho-hydroxy-cinnamic
      acid increased by up to two orders of magnitude in plants that were cold hardened
      in normal light. Both high light intensity and low temperature hardening caused
      an increase in the free and bound salicylic acid content of the leaves. This
      increase was most pronounced in plants that were cold treated in normal light.

PMID- 17537469
TI  - The effect of small interfering RNA (siRNA) against the Bcl-2 gene on apoptosis
      and chemosensitivity in a canine mammary gland tumor cell line.
AB  - The aim of this study was to investigate whether downregulation of Bcl-2
      expression by small interfering RNA (siRNA) against the canine Bcl-2 gene would
      enhance the apoptosis and sensitivity of a canine mammary gland tumor cell line
      (CF33) to doxorubicin. Transfections of CF33 with siRNA were performed using
      cationic liposomes. Sequence-specific downregulation of Bcl-2 expression was
      measured by semiquantitative RT-PCR and Western blot analysis. Total viable cells
      were determined by MTS assay and apoptotic cell rates were determined by the
      immunohistochemical analysis on ssDNA. Our data showed the siRNA downregulated
      Bcl-2 expression which increased apotosis and also increased the sensitivity of
      CF33 to doxorubicin. This study indicated that downregulation of Bcl-2 expression
      by siRNA would be useful as a new protocol to increase the effect of doxorubicin
      on treatment of canine mammary gland tumors, requiring a detailed evaluation of
      siRNA in vivo.

PMID- 17537470
TI  - [Chondrosarcoma of the nasal septum].
AB  - INTRODUCTION: A chondrosarcoma is rarely located in the nasal septum with only
      fifty cases reported in the literature. CASE REPORT: We report a new case of a
      seventy years old woman presenting with a large facial midline mass extending to
      the nasal cavity, having evolved for six months. Subsequent computed tomography
      revealed a mass destroying the nasal septum and extending to the endocrane.
      Intranasal biopsy revealed a chondrosarcoma. The extended work up revealed
      pulmonary metastasis. The course was not favourable and the patient died after
      one year. DISCUSSION: The bones of the pelvis and of the lower extremities are
      the most common localizations for chondrosarcoma. It is rarely located in the
      nasal septum. Histological analysis is required for the diagnosis. It is
      characterized clinically by local aggressiveness, frequent metastatic evolution,
      and poor prognosis. Surgical resection is reserved to operable cases.
      Chemotherapy and radiotherapy used as adjuvant treatment and palliation are not
      effective.

PMID- 17537471
TI  - The quercetin paradox.
AB  - Free radical scavenging antioxidants, such as quercetin, are chemically converted
      into oxidation products when they protect against free radicals. The main
      oxidation product of quercetin, however, displays a high reactivity towards
      thiols, which can lead to the loss of protein function. The quercetin paradox is
      that in the process of offering protection, quercetin is converted into a
      potential toxic product. In the present study, this paradox is evaluated using
      rat lung epithelial (RLE) cells. It was found that quercetin efficiently protects
      against H(2)O(2)-induced DNA damage in RLE cells, but this damage is swapped for
      a reduction in GSH level, an increase in LDH leakage as well as an increase of
      the cytosolic free calcium concentration. To our knowledge, this is the first
      study that indicates that the quercetin paradox, i.e. the exchange of damage
      caused by quercetin and its metabolites, also occurs in living lung cells.
      Following depletion of GSH in the cells by BSO pre-treatment, this quercetin
      paradox becomes more pronounced, confirming that the formation of thiol reactive
      quercetin metabolites is involved in the quercetin paradox. The quercetin paradox
      in living cells implies that the anti-oxidant directs oxidative damage
      selectively to thiol arylation. Apparently, the potential toxicity of metabolites
      formed during the actual antioxidant activity of free radical scavengers should
      be considered in antioxidant supplementation.

PMID- 17537472
TI  - Lysophosphatidylcholine produced by the phospholipase A2 isolated from Lachesis
      muta snake venom modulates natural killer activity as a protein kinase C
      effector.
AB  - We have showed that a phospholipase A(2) isolated from Lachesis muta snake venom,
      denoted LM-PLA(2)-I, had some biological effects. Here, we examined its effects
      on lymphocytes. Pre-incubation of human peripheral blood lymphocytes with LM
      PLA(2)-I plus phosphatidylcholine (PC) stimulated the natural killer (NK)
      activity. This was accompanied by DNA binding of nuclear transcription factor
      kappaB and the increase in PKC activity with translocation of the enzyme from the
      cytoplasma into the plasma membrane. These effects were reproduced when
      lymphocytes were pre-incubated with commercial lysophosphatidylcholine (LPC) and
      abolished by stausrosporin or p-bromophenacyl bromide. Evaluation of
      phosphorylated PKC isoforms showed that pre-incubation with LPC activated the
      autophosphorylation of the PKCzeta isoform. Taken together, these results confirm
      that the enzymatic activity of the phospholipase A(2) present in L. muta venom is
      for the biological activity of the snake venom, and strongly suggest that the LPC
      produced may be acting as a modulator of PKC isoforms.

PMID- 17537473
TI  - Efficacy of serum therapy on the treatment of rats experimentally envenomed by
      bristle extract of the caterpillar Lonomia obliqua: comparison with epsilon
      aminocaproic acid therapy.
AB  - Large number of accidents caused by contact with Lonomia obliqua caterpillars,
      with hemorrhagic complications, have occurred in southern Brazil. Based on
      Venezuelan expertise to treat Lonomia achelous envenomation, the use of the
      antifibrinolytic drug epsilon-aminocaproic acid (EACA) has been indicated to
      treat L. obliqua envenomation, although no evidence has been presented to justify
      its use. Specific antivenom (antilonomic serum (ALS)) that neutralizes toxins
      that cause envenomation was developed. To compare the effectiveness of such
      treatments, rats were injected i.d. with the bristle extract of L. obliqua
      caterpillars and treated 15 min, 1 and 6 h after with saline, ALS, EACA, or with
      both ALS and EACA. ALS elicited fibrinogen recovery and normalization of thrombin
      time (TT), prothrombin time (PT) and activated partial thromboplastin time
      (APTT), independent of when it was administered; however, hematocrit was
      decreased in the group treated later. Saline or EACA-treated groups presented
      neither fibrinogen recovery nor normalization of hemostatic parameters. A high
      death rate was observed in the group treated with EACA 15 min after the
      envenomation. Prolongation of TT and APTT observed in the group treated with EACA
      and ALS indicated that this association gave no benefit in relation to the group
      treated solely with ALS. The results presented herein suggest that ALS is the
      only effective treatment for envenomation caused by contact with Lonomia obliqua
      caterpillars and indicate that EACA should not be administered in the initial
      phase of envenomation.

PMID- 17537474
TI  - The effect of feeding piglets with the diet containing green tea extracts or
      coumarin on in vitro metabolism of aflatoxin B1 by their tissues.
AB  - To clarify whether enzymes involved in aflatoxin B1 (AFB1) metabolism in pigs
      respond to antioxidant agents, the effect of feeding piglets with diets
      containing green tea extracts (Sunphenon) and coumarin on in vitro AFB1
      metabolism by their liver and intestinal tissues was studied. The results showed
      that coumarin reduced AFB1-DNA adduct formation by both liver and intestinal
      microsomes, while Sunphenon did not have any effects. Both coumarin and Sunphenon
      enhanced the glutathione S-transferase (GST) activity to conjugate AFB1 to
      glutathione GSH in the intestine, although no effects were noted in the liver.
      Changes of the expression of mRNA of GSTA2 and GSTO1 were not in parallel with
      the observed changes of GST activity, suggesting that other GST subtypes are
      involved in the GST activity toward AFB1. As for lipophilic-free AFB1
      metabolites, coumarin reduced the liver microsomal conversion of AFB1 to
      aflatoxin M1 (AFM1) and aflatoxin Q1 (AFQ1), but Sunphenon exerted no effects.
      Both coumarin and Sunphenon enhanced the conversion of AFB1 to aflatoxicol in the
      liver. All the results suggest that feeding with a diet containing coumarin
      affects AFB1 metabolism to enhance AFB1 detoxification through the suppression of
      P450 enzyme activity in the liver and the enhancement of GST activity in the
      intestine. Feeding with a diet containing Sunphenon enhances AFB1 detoxification,
      but the effects are noted mainly in the intestine.

PMID- 17537475
TI  - Biochemical and biological characterization of the venoms of Bothriopsis
      bilineata and Bothriopsis taeniata (Serpentes: Viperidae).
AB  - Snake venom is a complex mixture containing diverse protein components with
      different structures and functions that are used for prey immobilization and
      death. Snake venoms from the family Viperidae cause pronounced local and systemic
      effects, such as pain, edema, hemorrhage and necrosis. Here, we investigated the
      enzymatic and biological activities of venoms from two Amazonian snakes,
      Bothriopsis bilineata and Bothriopsis taeniata. Both venoms presented high
      enzymatic activities for proteases kallikrein, thrombin and plasmin, low levels
      of trypsin, cathepsin C and leucine aminopeptidase activities, while lacked
      acetylcholinesterase activity. B. taeniata and B. bilineata crude venoms caused
      inflammation inducing neutrophil recruitment into peritoneal cavity of mice 4h
      after injection. Neutrophil recruitment induced by B. taeniata venom was
      accompanied by hemorrhage. EDTA treatment profoundly impaired neutrophil
      recruitment, suggesting the involvement of a metalloproteinase on venoms-induced
      neutrophil recruitment. Pretreatment with dexamethasone and zileuton, a 5
      lipoxygenase inhibitor, significantly reduced neutrophil migration, but
      indomethacin and montelukast, a cysteinyl leukotriene receptor antagonist, had no
      effect, suggesting the involvement of lipoxygenase-derived metabolites, probably
      LTB(4). Together, these results show that B. bilineata and B. taeniata venoms
      induce a marked inflammatory reaction, with leukocyte recruitment, and
      hemorrhage, which parallels to a high proteolytic activity found in these venoms.

PMID- 17537476
TI  - Droplet transport and coalescence kinetics in emulsions subjected to acoustic
      fields.
AB  - A method to aid the separation of the oil phase from aqueous emulsions using a
      low-intensity, resonant ultrasonic field has recently been developed. The density
      and compressibility difference between the dispersed and continuous phases within
      the emulsion results in a net force on the oil drops that pushes them toward the
      pressure antinodes of the standing-wave field, where coalescence subsequently
      occurs. A trajectory model is developed to predict the relative motion of drops
      subjected to the acoustic field. Such trajectories are sensitive to the physical
      properties and relative size of interacting drops, the initial configuration of
      the drops, and acoustic field parameters. Model predictions are validated by
      comparing experimentally observed trajectories with those predicted by the model.
      The modeling approach is then extended to determine the temporal evolution of the
      size of the region surrounding a target drop cleared by coalescence as a function
      of physical and acoustic field parameters. These results form the basis of a
      population balance model that attempts to track the size-evolution of a drop
      population coalescing under the influence of an acoustic field.

PMID- 17537477
TI  - Distribution and bioaccumulation of microcystins in water columns: a systematic
      investigation into the environmental fate and the risks associated with
      microcystins in Meiliang Bay, Lake Taihu.
AB  - For the purpose of understanding the environmental fate of microcystins (MCs) and
      the potential health risks caused by toxic cyanobacterial blooms in Lake Taihu, a
      systematic investigation was carried out from February 2005 to January 2006. The
      distribution of MCs in the water column, and toxin bioaccumulations in aquatic
      organisms were surveyed. The results suggested that Lake Taihu is heavily
      polluted during summer months by toxic cyanobacterial blooms (with a maximum
      biovolume of 6.7 x 10(8)cells/L) and MCs. The maximum concentration of cell-bound
      toxins was 1.81 mg/g (DW) and the dissolved MCs reached a maximum level of 6.69
      microg/L. Dissolved MCs were always found in the entire water column at all
      sampling sites throughout the year. Our results emphasized the need for tracking
      MCs not only in the entire water column but also at the interface between water
      and sediment. Seasonal changes of MC concentrations in four species of
      hydrophytes (Eichhornic crassipes, Potamogeton maackianus, Alternanthera
      philoxeroides and Myriophyllum spicatum) ranged from 129 to 1317, 147 to 1534,
      169 to 3945 and 124 to 956 ng/g (DW), respectively. Toxin accumulations in four
      aquatic species (Carassius auratus auratu, Macrobrachium nipponensis, Bellamya
      aeruginosa and Cristaria plicata) were also analyzed. Maximum toxin
      concentrations in the edible organs and non-edible visceral organs ranged from
      378 to 730 and 754 to 3629 ng/g (DW), respectively. Based on field studies in
      Lake Taihu, risk assessments were carried out, taking into account the WHO
      guidelines and the tolerable daily intake (TDI) for MCs. Our findings suggest
      that the third largest lake in China poses serious health threats when serving as
      a source of drinking water and for recreational use. In addition, it is likely to
      be unsafe to consume aquatic species harvested in Lake Taihu due to the high
      concentrations of accumulated MCs.

PMID- 17537478
TI  - A computational model for biofilm-based microbial fuel cells.
AB  - This study describes and evaluates a computational model for microbial fuel cells
      (MFCs) based on redox mediators with several populations of suspended and
      attached biofilm microorganisms, and multiple dissolved chemical species. A
      number of biological, chemical and electrochemical reactions can occur in the
      bulk liquid, in the biofilm and at the electrode surface. The evolution in time
      of important MFC parameters (current, charge, voltage and power production,
      consumption of substrates, suspended and attached biomass growth) has been
      simulated under several operational conditions. Model calculations evaluated the
      effect of different substrate utilization yields, standard potential of the redox
      mediator, ratio of suspended to biofilm cells, initial substrate and mediator
      concentrations, mediator diffusivity, mass transfer boundary layer, external load
      resistance, endogenous metabolism, repeated substrate additions and competition
      between different microbial groups in the biofilm. Two- and three-dimensional
      model simulations revealed the heterogeneous current distribution over the planar
      anode surface for younger and patchy biofilms, but becoming uniform in older and
      more homogeneous biofilms. For uniformly flat biofilms one-dimensional models
      should give sufficiently accurate descriptions of produced currents. Voltage- and
      power-current characteristics can also be calculated at different moments in time
      to evaluate the limiting regime in which the MFC operates. Finally, the model
      predictions are tested with previously reported experimental data obtained in a
      batch MFC with a Geobacter biofilm fed with acetate. The potential of the general
      modeling framework presented here is in the understanding and design of more
      complex cases of wastewater-fed microbial fuel cells.

PMID- 17537479
TI  - Enhanced Cr bioleaching efficiency from tannery sludge with coinoculation of
      Acidithiobacillus thiooxidans TS6 and Brettanomyces B65 in an air-lift reactor.
AB  - Bioleaching process has been demonstrated to be an effective technology in
      removing Cr from tannery sludge, but a large quantity of dissolved organic matter
      (DOM) present in tannery sludge often exhibits a marked toxicity to
      chemolithoautotrophic bioleaching bacteria such as Acidithiobacillus thiooxidans.
      The purpose of the present study was therefore to enhance Cr bioleaching
      efficiencies through introducing sludge DOM-degrading heterotrophic microorganism
      into the sulfur-based sludge bioleaching system. An acid-tolerant DOM-degrading
      yeast strain Brettanomyces B65 was successfully isolated from a local Haining
      tannery sludge and it could metabolize sludge DOM as a source of energy and
      carbon for growth. A combined bioleaching experiment (coupling Brettanomyces B65
      and A. thiooxidans TS6) performed in an air-lift reactor indicated that the rates
      of sludge pH reduction and ORP increase were greatly improved, resulting in
      enhanced Cr solubilization. Compared with the 5 days required for maximum
      solubilization of Cr for the control (single bioleaching process without
      inoculation of Brettanomyces B65), the bioleaching period was significantly
      shorten to 3 days for the combined bioleaching system. Moreover, little nitrogen
      and phosphorous were lost and the content of Cr was below the permitted levels
      for land application after 3 days of bioleaching treatment.

PMID- 17537480
TI  - Sources of fine urban particulate matter in Detroit, MI.
AB  - Data from the speciation trends network (STN) was used to evaluate the amount and
      temporal patterns of particulate matter originating from local industrial sources
      and long-range transport at two sites in Detroit, MI: Allen Park, MI, southwest
      of both Detroit and the areas of heavy industrial activity; Dearborn, MI, located
      on the south side of Detroit near the most heavily industrialized region. Using
      positive matrix factorization (PMF) and comparing source contributions at Allen
      Park to those in Dearborn, contributions made by local industrial sources (power
      plants, coke refineries, iron smelting, waste incineration), local area sources
      (automobile and diesel truck) and long range sources of PM(2.5) can be
      distinguished in greater Detroit. Overall, the mean mass concentration measured
      at Dearborn was 19% higher than that measured at Allen Park. The mass at Allen
      Park was apportioned as: secondary sulfate 31%, secondary nitrate 28%, soil 8%,
      mixed aged sea and road salts 4%, gasoline 15%, diesel 4%, and biomass burning
      3%. At Dearborn the mass was apportioned as: secondary sulfate 25%, secondary
      nitrate 20%, soil 12%, mixed aged sea and road salts 4%, gasoline 20%, diesel 8%,
      iron and steel, 5%, and mixed industrial 7%. The impact of the iron and steel,
      soil, and mixed aged sea and road salt was much higher at the Dearborn site than
      at the Allen Park site, suggesting that close proximity to a local industrial
      complex has a direct negative impact on local air quality.

PMID- 17537481
TI  - Bioaccumulation of arsenic compounds in aquacultural clams (Meretrix lusoria) and
      assessment of potential carcinogenic risks to human health by ingestion.
AB  - This study surveyed the total arsenic (As) and As species contents in clams
      (Meretrix lusoria) farmed in areas of hyperendemic blackfoot disease (BFD) in
      southwestern Taiwan. Total As and As species in sediment and pond water were also
      analyzed to examine the bioaccumulation of As in clams in their exposure
      environment. Moreover, potential carcinogenic risks associated with the ingestion
      of As in aquacultural clams were evaluated probabilistically. The average total
      As contents in medium-sized and small clams were 7.62 and 10.71 microg/g (dry
      wt), respectively. The content of the As species in this study was approximately
      61% of the total As content. The other unquantified As species are possibly
      arsenocholine, arsenosugar and arsenolipid. The average ratios of inorganic As
      contents to total As contents in clams ranged from 12.3% to 14.0% which are much
      higher than that found in the farmed oyster (Crassostrea gigas), indicating that
      humans may expose to larger quantities of inorganic As by ingesting the same
      amount of clam as oyster. Using different ingestion rates derived by the average
      consumption method and the questionnaire method, the estimated risks to human
      health associated with consuming clams from the BFD area ranging from slightly to
      largely exceed the standard target risk. Based on the estimation of the TR model,
      a 0.18g/day-person of the safe ingestion rate of clams in the BFD region is
      recommended.

PMID- 17537482
TI  - Concentrations of pentachlorophenol (PCP) in fish and shrimp in Jiangsu Province,
      China.
AB  - Pentachlorophenol (PCP) concentrations were determined in 55 samples of fish,
      shrimp, crabs, frogs and turtles collected in Jiangsu Province and 55 freshwater
      shrimp samples collected from the Huiming Fish Market, Nanjing, China between
      2003 and 2004. PCP concentrations ranged from less than the method detection
      limit (MDL: 0.5 microg/kg ww) to 61 microg/kg ww, with a mean of 5.2 microg/kg ww
      in 55 samples collected across Jiangsu Province and a mean of 0.5 microg/kg ww
      for freshwater shrimp collected from the Huiming Fish Market. Concentrations of
      PCP in common carp (Carassius auratus) were significantly greater than
      concentrations of PCP in other species from all of the areas studied. Grass carp
      (Ctenopharyngodon idella) contained the second greatest concentrations and
      crustacean species contained the least concentrations. Concentrations of PCP were
      greater in samples collected from Southern Jiangsu than those collected from
      other areas of Jiangsu Province. Concentrations of PCP in the freshwater shrimp
      (Macrobrachium nipponense) from the Huiming Fish Market were greater in March and
      September than those collected in June and December. Based on the allowable daily
      intake (ADI) set by the US National Academy of Science, current concentrations of
      PCP measured in aquatic products from Jiangsu Province presented minimus health
      risks to humans.

PMID- 17537483
TI  - The influence of iron and sulfur mineral fractions on carbon tetrachloride
      transformation in model anaerobic soils and sediments.
AB  - The objective of this research was to identify the dissolved species or solid
      phase mineral fraction(s) best correlated with rates of carbon tetrachloride (CT)
      reductive transformation in systems modeling sulfate-reducing and iron oxide-rich
      soils and sediments. We used sulfide (S(-II))-treated goethite as our model
      system, but also studied Fe(II) and S(-II)-treated goethite, Fe(II)-treated
      goethite, pure FeS, and Fe(II)-treated FeS in order to isolate and evaluate the
      influence of different mineral fractions on reaction rates. Initial rates of CT
      transformation were measured for different pH values and concentrations of added
      Fe(II), as well as different aging times and conditions. The following dissolved
      species and iron and sulfur mineral fractions were quantified and compared with
      CT transformation rates: aqueous Fe(2+) and S(-II), surface associated Fe(II)
      (including weakly and strongly bound Fe(II)), FeS(s), and Cr(II) reducible solid
      phase S. Over the pH range of 6-10, CT transformation rates were correlated with
      surface associated Fe(II), while at pH 8, rates were correlated with weakly bound
      Fe(II). Aging of S(-II)-treated goethite led to oxidation of surface sulfur and a
      change in the concentration of weakly bound Fe(II), but did not change the
      relationship between initial rates and weakly bound Fe(II). The results of this
      research suggest that surface associated Fe(II) and weakly bound Fe(II) could
      serve as indicators of the potential for abiotic CT dechlorination in natural
      soils under sulfate-reducing conditions.

PMID- 17537484
TI  - Thyroid ultrasound volume, structure and function after long-term high exposure
      of large population to polychlorinated biphenyls, pesticides and dioxin.
AB  - We examined 2,046 adults (834 males and 1,212 females aged 20-75 years) from
      polluted district in East Slovakia (POLL) and two neighboring upstream and upwind
      located districts of background pollution (BCGR). By ultrasound we estimated the
      thyroid volume (ThV), hypoechogenicity (HYE), nodules and cysts. Serum levels of
      thyrotropin (TSH), thyroperoxidase antibodies (TPOab) and thyroglobulin were
      estimated by electrochemiluminiscent assay and these of 15 PCB congeners, p,p'
      DDE, p,p'-DDT, hexachlorobenzene (HCB) and hexachlorocyclohexane by high
      resolution gas chromatography. In 320 subjects also selected hydroxylated and
      methylsulfonated PCB metabolites, polychlorinated dibenzo-dioxins (PCDDs), 
      furans (PCDFs), five dioxin-like coplanar and eight mono-ortho PCB congeners were
      estimated. Urinary iodine was measured by automatic microplate method. Reciprocal
      positive association was found between three major POPs (PCBs, DDE and HCB), the
      levels of these and also PCDDs plus PCDFs in polluted area being considerably
      higher than in background pollution area. ThV in groups of males and females from
      POLL with high PCBs level was significantly higher (p<0.001 by t-test) then in
      age and sex matched groups from BCGR with low PCBs level. In 1,048 males and
      females aged <60 years with serum PCBs level >1,000 ng g(-1) lipid (median=1,756
      ng g(-1)) a significant effect of age on ThV was found (p<0.01 by ANOVA), while
      in 921 respective subjects with PCBs level <1,000 ng g(-1) (median=661 ng g(-1))
      it was not. These findings supported the view on the additional effect of PCBs on
      ThV other than that of age. Since the urinary iodine in both districts showed
      optimal range, any interfering effect of unsatisfactory iodine intake on ThV may
      be excluded. The frequency of autoimmune thyroiditis signs such as HYE, increased
      serum level of TPOab and TSH resulting in subclinical or overt thyroid
      hypofunction was positively associated with sex, age and organochlorine levels.
      The increase of such frequency in males with POPs levels was much more abrupt
      than that in females. No considerable differences in the frequency of thyroid
      nodules as related to PCBs level were found.

PMID- 17537485
TI  - Intracranial leptomeningeal metastasis from thymic carcinoma: case report and
      review.
AB  - BACKGROUND: Thymic carcinoma is an uncommon malignant tumor of the anterior
      mediastinum. Meningeal metastasis from this type of neoplasm is extraordinarily
      rare and the prognosis is abysmal. CASE DESCRIPTION: This article presents the
      case of a 45-year-old man with known metastatic thymic carcinoma who presented
      with intractable headaches. An MRI scan was highly suggestive of a meningioma,
      and it was initially suspected that this patient had 2 primary tumors. Surgical
      resection of the mass both demonstrated a metastatic thymic lesion and
      ameliorated the patient's quality of life. CONCLUSION: The authors report a case
      of intracranial meningeal metastasis from a lymphoepithelioma-like poorly
      differentiated metastatic thymic carcinoma, which was treated by resection and
      WBRT. A review of the current literature revealed no other cases of this uncommon
      alhistologic subtype of thymic carcinoma metastatic to the cranium. The
      incidence, histologic classification of subtypes, and treatment are discussed.
      This case also illustrates the importance of maintaining a high degree of
      suspicion for a metastasis in patients with known primary malignancy who present
      with an MRI highly suspicious for meningioma.

PMID- 17537486
TI  - Cerebellar pleomorphic xanthoastrocytoma: case report and literature review.
AB  - BACKGROUND: PXA generally has histologic features characteristic of benign
      biological behavior, although malignant forms have been reported. This neoplasm
      has also been observed in atypical locations. METHODS: The authors report a case
      of cerebellar PXA with rapid malignant transformation in a 58-year-old woman and
      review the rare presentations and atypical features of this tumor. RESULTS: Among
      the "unusual" locations, the most frequent is the cerebellum with 15 cases having
      been described, 9 in adults, with an average age of 33 years. In contrast,
      supratentorial forms had a younger age profile (26 years). The time from onset of
      symptoms to diagnosis was approximately 5.3 months. PXA in the posterior fossa
      had a higher rate of solid enhancing tumor (9/14). Regarding histologic
      appearance, two thirds were composite lesions. CONCLUSIONS: The clinicopathologic
      features of cerebellar PXA show some differences from PXA located in the cerebral
      hemispheres. Recognizing the potential for PXA to present with unusual
      manifestations, regardless of location, has an obvious impact on the accuracy of
      diagnosis.

PMID- 17537487
TI  - Retrospective analysis of a new antibiotic chemoprophylaxis regimen in 170
      patients undergoing endoscopic endonasal transsphenoidal surgery.
AB  - BACKGROUND: The aim of this study is to evaluate the rate of infectious
      complications post endoscopic transspheinodal neurosurgery in patients receiving
      a new antibiotic chemoprophylaxis regimen. METHODS: Clinical records of 170
      patients who received prophylaxis with a third-generation cephalosporin plus
      aminoglycoside (160 cases) or alone (10 cases) were retrospectively analyzed.
      Twenty-eight patients (16.4%) had CSF leakage. The postsurgical follow-up ranged
      from 3 months to 4 years. RESULTS: Of 170 patients, 2 (1.17%) developed
      infectious complications: 1 case of meningitis by Staphylococcus epidermidis and
      1 case of sphenoid sinusitis (without microbiological diagnosis). In addition,
      asymptomatic sphenoid sinusitis was diagnosed in 2 other patients. The cost
      ranged from 22.50 to 33.34 euros/d. CONCLUSIONS: The rate of infectious
      complications was very low in patients receiving prophylaxis with a third
      generation cephalosporin plus aminoglycoside or alone; because of the broad
      spectrum of antibiotics and their high cost, this regimen could be used in at
      risk patients (eg, smokers, patients with cerebrospinal leak, or patients with
      Cushing diseases).

PMID- 17537488
TI  - Petrous carotid artery pseudoaneurysm in bilateral carotid fibromuscular
      dysplasia: treatment by means of self-expanding covered stent.
AB  - BACKGROUND: Pseudoaneurysms of the petrous carotid artery may occur in the
      setting of trauma, dissection, invasive tumors, or as a complication of surgery.
      These aneurysms may grow and constitute a potential source of thromboembolic
      complications or rupture. CASE DESCRIPTION: We present a patient with bilateral
      carotid FMD presenting with a large petrous pseudoaneurysm. Because carotid
      occlusion was not appropriate, a self-expandable covered stent was implanted.
      This treatment allowed complete exclusion of the pseudoaneurysm and preservation
      of the parent artery. CONCLUSION: The accepted treatment of psuedoaneurysms
      located at petrous ICA is either sacrifice of the carotid artery or exclusion of
      the aneurysm from the preserved carotid artery. These procedures have specific
      limitations, and they are technically demanding and associated with a substantial
      morbidity rate. The endovascular treatment of these lesions is the preferred
      alternative. Among the various endovascular techniques that have been tested so
      far, we propose self-expandable covered stents as ideal for treating arterial
      aneurysms and pseudoaneurysms of the petrous and cavernous carotid segments.

PMID- 17537489
TI  - Neural stem cell markers, nestin and musashi proteins, in the progression of
      human glioma: correlation of nestin with prognosis of patient survival.
AB  - BACKGROUND: The IF protein nestin and the RNA-binding protein musashi are
      expressed by neural progenitor cells during CNS development. Their expression in
      glial tumors was evaluated by immunohistochemistry, and the histopathological
      scores correlated with levels of cysteine cathepsins that are known prognostic
      markers in several tumors. METHODS: The levels of nestin, musashi, and cathepsins
      B and L were assessed by immunohistochemical analysis of biopsies from 87
      patients with primary CNS tumors. To confirm the immunohistochemical data, nestin
      expression was analyzed by real-time PCR in 12 brain tumor biopsies. The exact
      location of nestin-positive cells was determined by mapping the distribution of
      nestin in a highly invasive human glioma xenograft model. RESULTS: Immunostaining
      revealed nestin to be expressed in 95.8% and musashi in 80% of the patient
      biopsies. The total IHC score for nestin was significantly higher in high- than
      in low-grade tumors (P < .0001). No difference was observed for musashi (P =
      .11). Real-time PCR of nestin expression confirmed the immunohistochemical data.
      Nestin expression was shown to be a strong prognostic marker for decreased
      overall survival (P = .0001), whereas musashi expression has no prognostic
      significance. Moreover, nestin was shown by Cox regression analysis to be a
      stronger prognostic marker than cathepsins B and L. IHC staining of nestin in a
      xenograft model showed that its expression is localized mainly in the invasive
      tumor cells at the tumor periphery. CONCLUSIONS: Nestin is shown to be a strong
      prognostic marker for glioma malignancy. The presented data links the invasive
      glioma cells to CNS precursor cells, indicating that the most malignant cells in
      the gliomas may well be closely related to the glioma stem cells.

PMID- 17537490
TI  - Pitfalls in the preoperative evaluation of subarachnoid hemorrhage without
      digital subtraction angiography: report on 2 cases.
AB  - BACKGROUND: Digital subtraction angiography has been used in the diagnosis of
      aneurysmal SAH and as a preoperative imaging method. However, new methods such as
      MRA and CTA are now deemed by many institutions to provide sufficient information
      to allow surgery to go ahead without a preliminary DSA scan. We report on 2 cases
      of SAH in which there were additional lesions that were difficult to evaluate
      because of the lack of DSA information. CASE DESCRIPTIONS: The fist patient
      demonstrated SAH with IVH. Computed tomographic angiography revealed an ACoA
      aneurysm with a bleb. We first thought that the SAH and IVH were both caused by a
      ruptured ACoA aneurysm but noted that hemorrhage pattern was inconsistent with
      the location and orientation of the aneurysm. A DSA scan revealed a dural
      arteriovenous fistula in the region of the craniocervical junction, supplied by
      the right occipital artery. We surmised that the SAH and IVH were caused by a
      large varix of DAVF and that the ACoA aneurysm would be unruptured. The second
      patient presented with a 1-week history of headaches and nausea and was diagnosed
      to have an SAH caused by a ruptured MCA aneurysm. We suspected vasospasm in the
      second portion of the MCA on CTA, but could not precisely evaluate the affected
      lesions. A diffusion-weighted MRI scan 4 days after surgery revealed a high
      intensity area in the region of the right MCA. The MCA had already seemed to be
      affected at admission because vasospasm rarely develops within 4 days of the
      onset of SAH. CONCLUSIONS: As long as the CTA scan is of adequate quality and
      shows the aneurysm clearly, we consider that an additional DSA provides little
      useful information for surgery. However, in such cases, the information from a
      DSA scan is needed for the evaluation of secondary factors that are not directly
      associated with the aneurysm.

PMID- 17537491
TI  - UCN-01 in combination with topotecan in patients with advanced recurrent ovarian
      cancer: a study of the Princess Margaret Hospital Phase II consortium.
AB  - BACKGROUND AND OBJECTIVE: UCN-01 is a staurosporine analogue shown to abrogate
      the G2 checkpoint through inhibition of cyclin-dependent kinases. Preclinical
      evidence suggests synergy between UCN-01 and cytotoxic chemotherapy. Topotecan is
      an active agent in ovarian cancer. This phase II study was conducted to
      investigate the safety and efficacy of topotecan and UCN-01 in patients with
      advanced ovarian cancer. METHODS: A two-stage phase II trial was designed for
      patients with advanced ovarian cancer with progressive disease despite prior
      treatment with platinum and paclitaxel. Patients with advanced ovarian cancer
      were treated with topotecan, 1 mg/m(2) IV, days 1 to 5, and UCN-01 70 mg/m(2) on
      day 1 of the first cycle, and 35 mg/m(2) on day 1 of all subsequent cycles.
      Treatment was repeated on a 3-week cycle. The primary objective of this study was
      objective response rate while secondary objectives included rates of stable
      disease, duration of response, progression-free and overall survival, as well as
      toxicity. Tumor biopsy specimens were also collected where possible for molecular
      correlative studies. RESULTS: Twenty-nine patients are evaluable for toxicity and
      efficacy. Three patients (10%) achieved a partial response. The median time to
      progression was 3.3 months (95% CI 1.5-NA), and the median overall survival was
      9.7 months (95% CI: 7.5-15.3). The most common grade 3-4 toxicities were
      neutropenia (79%), anemia (41%), thrombocytopenia (14%), hyperglycemia (10%), and
      pain (10%). CONCLUSION: The combination of UCN-01 and topotecan is generally well
      tolerated, however, this combination is not considered to have significant
      antitumor activity against advanced ovarian cancer.

PMID- 17537492
TI  - Primitive neuroectodermal tumor of the uterus.
AB  - BACKGROUND: : Primitive peripheral neuroectodermal tumors (PNETs) of the uterus
      are rare. Recent data have demonstrated improved response rates with adjuvant
      chemotherapy. CASE: : A 26-year-old, gravida 2, para 1, Filipina female underwent
      an emergent cesarean section for fetal indications. Intraoperative findings were
      remarkable for a soft tissue mass in the lower uterine segment. Histologic
      features, immunohistochemical findings, and chromosomal analysis were consistent
      with a PNET. The patient underwent radical surgery, adjuvant chemotherapy with
      vincristine, doxorubicin, cyclophosphamide, ifosfamide and etoposide (VAC/IE),
      and whole pelvic radiation therapy. CONCLUSION: : Only 14 case reports of
      primitive neuroectodermal tumors of the uterus have been published in the English
      literature to date. No definitive conclusions concerning the therapeutic
      management and prognosis have been ascertained.

PMID- 17537493
TI  - The blockade of AMPA-kainate and NMDA receptors in the dorsal periaqueductal gray
      reduces the effects of diazepam withdrawal in rats.
AB  - It is well established that the most persistent sign of withdrawal from chronic
      benzodiazepine use in humans is anxiety. In contrast to other types of drugs of
      abuse, the emergence of this anxiety does not seem to be linked directly to
      alterations in the levels of dopamine in the mesolimbic system. Some studies have
      proposed that fear-like behaviors elicited by benzodiazepine withdrawal could be
      the result either of alterations in the sensitivity of GABAA receptors or in the
      neuronal hyperexcitability that results from neuroadaptative responses to chronic
      treatment, probably mediated by glutamate. The increased fear-like behaviors
      induced by benzodiazepine withdrawal are similar to the defense reaction
      displayed by animals exposed to dangerous situations or submitted to electrical
      or chemical stimulation of the dorsal periaqueductal gray (dPAG), a key structure
      of the brain aversive system. However, the involvement of the dPAG in drug abuse
      has been investigated only in the context of the physical effects of drug
      dependence. Thus, in this study we investigated the effects of injections into
      the dPAG of the glutamic acid diethyl ester (GDEE) and 2-amino-7
      phosphonoheptanoate (AP-7) (AMPA-kainate and NMDA receptors antagonists,
      respectively) on fear-like behaviors promoted by benzodiazepine withdrawal in
      rats submitted to aversive events (foot-shocks) immediately before chronic
      diazepam administration in a conditioning place-preference paradigm, using a
      light-dark box. Our results showed that inhibition of the glutamatergic
      neurotransmission in the dPAG reduces the consequence of the diazepam withdrawal
      in rats, implicating the excitatory amino acids of the dPAG in the modulation of
      the aversive state induced by benzodiazepine drugs withdrawal.

PMID- 17537494
TI  - Acute effects of AMPA-type glutamate receptor antagonists on intermale social
      behavior in two mouse lines bidirectionally selected for offensive aggression.
AB  - Involvement of AMPA-type glutamate receptors in the regulation of social behavior
      has been suggested by experiments with mice deficient for the GluR-A subunit
      containing AMPA receptors showing reduced intermale aggression. In the present
      study, effects of AMPA receptor antagonists on mouse social behavior towards
      unfamiliar Swiss-Webster males on a neutral territory were tested using male
      subjects from the Turku Aggressive (TA) and Turku Non-Aggressive (TNA) mouse
      lines bidirectionally selected for high and low levels of offensive aggression.
      The drugs were the competitive antagonists 6-cyano-7-nitroquinoxaline-2,3-dione
      (CNQX) and 2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzo[f]quinoxaline-7-sulfonamide
      (NBQX), and the non-competitive antagonist 4-(8-methyl-9H-1,3-dioxolo[4,5
      h][2,3]benzodiazepin-5-yl)-benzenamine (GYKI 52466). In TA mice, CNQX and NBQX
      decreased the biting component of aggressive structure, while GYKI 52466
      suppressed all aggressive manifestations. All drugs increased anxiety-like
      behavior towards the partner. In TNA mice, NBQX activated mouse social behavior
      and ambivalent aggression, while CNQX and GYKI 52466 only increased anxiety.
      Thus, AMPA receptor antagonists affect aggressive behaviors in TA mice supporting
      the idea that AMPA receptors are involved in the modulation of agonistic
      impulsive behavioral pattern. GYKI 52466 appeared to be the most selective and
      efficacious in suppressing the aggression.

PMID- 17537495
TI  - Changes in Proenkephalin mRNA expression in forebrain areas after amphetamine
      induced behavioural sensitization.
AB  - Acute and repeated psychostimulant administration induces a long-lasting enhanced
      behavioural response to a subsequent drug challenge, known as behavioural
      sensitization. This phenomenon involves persistent neurophysiological
      adaptations, which may lead to drug addiction. Brain dopaminergic pathways have
      been implicated as the main neurobiological substrates of behavioural
      sensitization, although other neurotransmitters and neuromodulators may also
      participate. In order to investigate a possible involvement of opioid systems in
      amphetamine (AMPH) behavioural sensitization, we studied the AMPH-induced changes
      in Proenkephalin (Pro-Enk) mRNA expression in forebrain areas in both drug-naive
      and AMPH-sensitized rats. Male Sprague-Dawley rats were sensitized to AMPH by
      means of a single AMPH (1 mg/kg s.c.) injection and the same dose was injected 7
      days later to assess the expression of sensitization. Pro-Enk mRNA levels were
      evaluated by in situ hybridization in coronal brain sections. AMPH injection
      induced an increase in Pro-Enk mRNA expression in the nucleus accumbens and the
      medial-posterior caudate-putamen in drug-naive rats. Challenge with AMPH to rats
      injected 1 week earlier with AMPH induced motor sensitization and increased and
      decreased Pro-Enk mRNA expression in the prefrontal cortex and the anterior
      medial caudate-putamen, respectively. Our results suggest that alterations in
      cortical and striatal enkephalinergic systems could contribute to the expression
      of AMPH behavioural sensitization.

PMID- 17537496
TI  - Effects of dietary energy source on energy balance, metabolites and reproduction
      variables in dairy cows in early lactation.
AB  - This paper summarizes three recent studies by the same authors with the objective
      to study the effect of dietary energy source on the energy balance (EB) and risk
      for metabolic and reproductive disorders in dairy cows in early lactation. The
      first study, a literature survey, illustrated that feeding extra glucogenic
      nutrients relative to lipogenic nutrients, decreased milk fat and seems to
      decrease plasma non-esterified fatty acid (NEFA) and beta-hydroxybutyrate (BHBA)
      concentration. However studies are scarce and mostly confound the effect of
      energy source with level of energy intake, compromising eventual effects on EB
      and fertility. Therefore, in the second study, 16 dairy cows were either fed a
      glucogenic or a lipogenic diet (isocaloric) and EB was determined in climate
      controlled respiration chambers from week 2 until 9 of lactation. Glucogenic diet
      decreased milk fat yield and milk energy and tended to decrease body fat
      mobilization compared with lipogenic diet. The objective of the third study was
      to study the effect of dietary energy source on EB, metabolites and reproduction
      variables. Dairy cows (n=111) were fed glucogenic, lipogenic or mixed diet from
      week 3 until week 9 relative to calving. Multiparous cows fed glucogenic diet had
      lower milk fat yield, higher calculated EB, and lower plasma NEFA, BHBA and liver
      triacylglyceride concentration and tended to have fewer days to first postpartum
      ovulation. In conclusion, increasing the glucogenic nutrient availability
      improved the EB and had potential to reduce the risk for metabolic disorders and
      to improve reproductive performance in dairy cows.

PMID- 17537497
TI  - Effect of vitrification solutions and cooling upon in vitro matured prepubertal
      ovine oocytes.
AB  - The vitrification procedure effects on molecular and cytoskeletal components and
      on developmental ability of in vitro matured prepubertal ovine oocytes were
      evaluated. MII oocytes were divided into three groups: (1) vitrified in cryoloops
      (VTR); (2) exposed to vitrification solutions and rehydrated without being
      plunged into liquid nitrogen (EXP); (3) without further treatment as a control
      (CTR). Two hours after treatment, membrane integrity, assessed by propidium
      iodide/Hoechst staining, was lower in VTR and EXP than in CTR (70.6%, 88.5% and
      95.2%, respectively). Cleavage rate after fertilization was statistically
      different among all groups (21.4%, 45.4% and 82.8% for VTR, EXP and CTR groups
      respectively; P<0.01). Blastocyst rate in VTR (0.0%) and EXP (2.8%) groups was
      lower (P<0.01) than in CTR (22.8%). Maturation promoting factor activity was
      lower (P<0.01) in VTR and EXP groups compared with CTR at both 0 h (82.2%, 83.6%
      and 100%, respectively) and 2 h (60% and 53.9% and 100%, respectively) after
      warming. Immediately after warming VTR and EXP oocytes showed a lower rate of
      normal spindle and chromosome configuration compared to CTR (59.1%, 48.0% and
      83.3%, respectively; P<0.01). After 2 h of culture in standard conditions the
      percentage of oocytes with normal spindle and chromosome organization decreased
      in both VTR and EXP groups compared to CTR (36.4%, 42.8% versus 87.5%,
      respectively). In conclusion the exposition to the tested cryoprotectant solution
      and the vitrification in cryoloops modified cytoskeletal components and alter
      biochemical pathways that compromise the developmental capacity of prepubertal in
      vitro matured ovine oocytes.

PMID- 17537498
TI  - A critique of Mark D. Allen's "the preservation of verb subcategory knowledge in
      a spoken language comprehension deficit".
AB  - Allen [Allen, M. (2005). The preservation of verb subcategory knowledge in a
      spoken language comprehension deficit. Brain and Language, 95, 255-264.] reports
      a single patient, WBN, who, during spoken language comprehension, is still able
      to access some of the syntactic properties of verbs despite being unable to
      access some of their semantic properties. Allen claims that these findings
      challenge linguistic theories which assume that much of the syntactic behavior of
      verbs can be predicted from their meanings. I argue, however, that this
      conclusion is not supported by the data for two reasons: first, Allen focuses on
      aspects of verb syntax that are not claimed to be influenced by verb semantics;
      and second, he ignores aspects of verb syntax that are claimed to be influenced
      by verb semantics.

PMID- 17537499
TI  - Neurology of affective prosody and its functional-anatomic organization in right
      hemisphere.
AB  - Unlike the aphasic syndromes, the organization of affective prosody in brain has
      remained controversial because affective-prosodic deficits may occur after left
      or right brain damage. However, different patterns of deficits are observed
      following left and right brain damage that suggest affective prosody is a
      dominant and lateralized function of the right hemisphere. Using the Aprosodia
      Battery, which was developed to differentiate left and right hemisphere patterns
      of affective-prosodic deficits, functional-anatomic evidence is presented in
      patients with focal ischemic strokes to support the concepts that (1) affective
      prosody is a dominant and lateralized function of the right hemisphere, (2) the
      intrahemispheric organization of affective prosody in the right hemisphere, with
      the partial exception of Repetition, is analogous to the organization of
      propositional language in the left hemisphere and (3) the aprosodic syndromes are
      cortically based as part of evolutionary adaptations underlying human language
      and communication.

PMID- 17537500
TI  - "I wanted to get to know her better": adolescent boys' dating motives,
      masculinity ideology, and sexual behavior.
AB  - Little is known about adolescent boys' motives for dating, although stereotypical
      portrayals highlight a desire for sexual behavior. This issue was examined from a
      normative perspective that connected dating motives to intercourse motives,
      masculinity, and dating and sexual behaviors. Data from 105 racially and
      economically diverse 10th-grade boys were analyzed. Results indicated that the
      most commonly endorsed motives for dating and intercourse focused on the boys'
      partners and relationships, and that boys' motives tended to be consistent across
      dating and sexual behavior. Peer conformity motives were less frequently endorsed
      and typically co-occurred with other motives. Findings revealed few connections
      between motives, masculinity ideology, and sexual behaviors. Discussion
      highlights the importance of moving beyond stereotypes when examining boys'
      romantic and sexual motives.

PMID- 17537501
TI  - DNA adducts and polycyclic aromatic hydrocarbon (PAH) tissue levels in blue
      mussels (Mytilus spp.) from Nordic coastal sites.
AB  - DNA adducts in gills and digestive gland, as well as polycyclic aromatic
      hydrocarbon (PAH) tissue levels were analysed in blue mussels (Mytilus spp.) from
      Nordic coastal areas (Iceland, Norway and Sweden) with diffuse or point sources
      of PAHs of various origins. Both DNA adduct and PAH tissue levels were generally
      low, indicating low PAH exposure to the mussels in the areas studied. DNA adducts
      were found to be higher in gills than in digestive gland of the mussels at all
      sites studied. Elevated DNA adduct levels in gills were found at 6 sites out of
      18 compared to reference sites in respective coastal zones. Adduct levels ranged
      from 0.5 to 10 nmol adducts/mol normal nucleotides, being highest in mussels from
      Reykjavik harbour, Iceland (intertidal mussels), and from Fiskaatangen, Norway
      (subtidal mussels). Total PAH tissue levels in the mussels ranged between 40 and
      11,670 ng/g dry wt., and were significantly correlated with DNA adduct levels
      (r(2)=0.73, p<0.001). PAH ratio values indicated that the PAHs were in most cases
      of pyrolytic origin, but with petrogenic input near harbours and an oil refinery.

PMID- 17537502
TI  - Immunological responses in mice to full-thickness corneal grafts engineered from
      porcine collagen.
AB  - Tissue-engineered (TE) corneas were fabricated from porcine collagen cross-linked
      with 1-ethyl-3-(3-dimethyl aminoproplyl)carbodiimide (EDC) and N
      hydroxysuccinimide (NHS), and were transplanted into BALB/c mice orthotopically
      using a full-thickness penetrating keratoplasty (PKP) procedure. The
      biocompatibility was evaluated by assessing both local and systemic immune
      responses. Myeloid cells including granulocytes and macrophages were the main
      infiltrating cells in recipient cornea and in retro-TE corneal membrane which
      developed 7-10 days post surgery. Sodium citrate was found to be effective in
      reducing fibrin accumulation in anterior chamber post grafting at early time
      points, but it did not prevent formation of the retro-TE corneal membrane. No
      significant T cell activation was observed in the submandibular draining lymph
      nodes (SMDLN) by flow cytometry. Anti-porcine type I collagen IgG antibodies were
      detected in the serum of grafted mice from 2 weeks post grafting and the
      concentration of antibodies increased with time. Overall, porcine collagen
      EDC/NHS TE corneas were tolerated well in murine recipients, causing mainly a
      self-limiting local innate immune response and a low-grade humoral response with
      little evidence of sustained T cell activation. Retro-TE corneal membrane
      formation was the main complication and barrier to clarity.

PMID- 17537503
TI  - Re: Age-related incidence curve of hospitalized Shaken Baby Syndrome cases:
      convergent evidence for crying as a trigger to shaking (Barr, Trent, & Cross,
      2006).

PMID- 17537504
TI  - Re-referral to child protective services: the influence of child, family, and
      case characteristics on risk status.
AB  - INTRODUCTION: This study examines child, family, and case characteristics that
      impact rates of re-referral to Child Protective Services (CPS) using data on all
      closed CPS investigations for the state of Rhode Island between 2001 and 2004.
      METHOD: A longitudinal dataset of all referrals to CPS was created using state
      submissions to the National Child Abuse and Neglect Data System (NCANDS). After
      excluding children whose initial CPS investigation resulted in removal from the
      home, a Cox proportional hazards model was tested to examine factors impacting
      the likelihood of re-referral. RESULTS: Consistent with other research in this
      area, the initial 6-month period following case disposition is the period of
      greatest risk of re-referral. Approximately 13% of cases experienced a recurrent
      allegation during the first 6-month period; an additional 14% experienced a re
      referral over the following 12-month period; 7% during the next 12-month period.
      Family poverty was the strongest predictor of re-referral, though a number of
      child and case characteristics were significantly related to recurrence. Cases
      that were substantiated at index were significantly less likely to result in a
      new allegation, though substantiated cases of physical abuse or those receiving
      post-investigation services were at higher risk. CONCLUSIONS: Children from
      families facing multiple stressors (e.g., low SES, parental substance abuse child
      disability) are at highest risk of re-referral to CPS and may benefit from the
      development of preventive services targeted immediately following case closings
      within CPS.

PMID- 17537505
TI  - Parental self-confidence, parenting styles, and corporal punishment in families
      of ADHD children in Iran.
AB  - OBJECTIVE: This study examines the relationship between parental self-confidence,
      warmth, and involvement, and corporal punishment in families of children with
      attention deficit/hyperactivity disorder (ADHD). METHOD: The diagnosis of ADHD
      was established through clinical interviews with the parents, children, and
      teachers, according the criteria in DSM-IV-TR. This diagnosis was also
      established by having the parents complete the Conners' Parent Rating Scale, and
      the teachers complete the Conners' Teacher Rating Scale. Two groups of Iranian
      parents, one group with children who have ADHD (N=130) and a control group
      (N=120), completed questionnaires measuring parental self-confidence and
      parenting styles. RESULTS: Parents of children with ADHD were found to have lower
      self-confidence and less warmth and involvement with their children, and used
      corporal punishment significantly more than the parents of control children.
      CONCLUSIONS: The study provides strong evidence that children with ADHD are at
      considerable risk of abuse by their parents. Rather than focusing only on the
      child's ADHD, treatment may also need to address the parents' functioning.

PMID- 17537506
TI  - Childhood abuse, chronic pain, and depression in the National Comorbidity Survey.
AB  - OBJECTIVE: The current study examined the effects of childhood sexual and
      physical abuse on reports of pain in men and women (N=1,727). METHODS: Data from
      the National Comorbidity Survey, a nationally representative sample, were
      utilized. Childhood experiences of physical and sexual abuse were assessed, and
      pain reports in relation to current health problems were obtained. Regression and
      mediation analyses were used to examine the relationship between childhood abuse
      and current pain reports and to determine whether depression mediated this
      relationship. RESULTS: Individuals who experienced abuse reported more health
      problems compared to those participants without abuse histories. Among
      participants with a current health problem, those who experienced abuse reported
      more pain compared to those participants without abuse histories. Because
      childhood abuse is associated with depression and depression is associated with
      more reported pain, the influence of depression on the relationship between
      childhood abuse and adult pain reports was examined. After controlling for
      differences between the abused and non-abused participants on specific health
      problems, depression was not found to have mediated the relationship.
      CONCLUSIONS: Childhood abuse was associated with more reported pain. The higher
      rate of depression found among adults who experienced childhood abuse was not the
      primary factor for these increased pain reports. Rather, childhood abuse and
      depression independently contributed to pain reports. Treatment of both
      underlying problems (i.e., pain and depression) is recommended in addressing the
      needs of abused individuals with these comorbid disorders.

PMID- 17537507
TI  - Multiple victimization experiences of urban elementary school students:
      associations with psychosocial functioning and academic performance.
AB  - OBJECTIVE: This study explored the victimization experiences of urban elementary
      school students to determine whether subsets of youth emerged with similar
      victimization profiles (e.g., no victimization, multiple types of victimization).
      It also evaluated whether multiple victimization was associated with greater
      psychological distress and lower academic performance. METHODS: Participants were
      689 fifth grade students from an urban, ethnically diverse school district in the
      Northeast. Youth completed self-report measures in school about bullying
      victimization, victimization in the home and community, and psychosocial
      functioning. RESULTS: Cluster analysis suggested the existence of three distinct
      youth profiles: those with minimal victimization, those victimized primarily by
      their peers, and those with multiple types of victimizations. As hypothesized,
      youth with multiple victimizations experienced more psychological distress and
      earned lower grades than their peers. CONCLUSIONS: Findings highlight the
      heterogeneity of youth victimization experiences and their relations to
      functioning, and have implications for treatment planning among practitioners
      working with youth.

PMID- 17537508
TI  - Re-victimization patterns in a national longitudinal sample of children and
      youth.
AB  - OBJECTIVE: To understand to the degree to which a broad variety of
      victimizations, including child maltreatment, conventional crime, peer, and
      sexual victimizations, persist for children from 1 year to the next. DESIGN: A
      national sample of 1467 children aged 2-17 recruited through random digit dialing
      and assessed via telephone interviews (with caretakers and youth themselves)
      about a comprehensive range of victimization experiences in the previous year,
      and then re-assessed (72.3% of baseline sample) after a 1-year interval. RESULTS:
      The risk for re-victimization in Year 2 was high for children victimized in Year
      1, with risk ratios ranging from 2.2 for physical assault to 6.9 for sexual
      victimization. Victimization of any one type left substantial vulnerability even
      for different types of subsequent re-victimization (e.g., property crime
      victimization was associated with higher risk of sexual victimization the next
      year). Children with four or more types of victimization in Year 1 ("poly
      victims") were at particularly high risk of persisting poly-victimization.
      Persisting poly-victimization was more likely for children who scored high on
      anger/aggression and who had recent life adversities. Desistence from poly
      victimization was associated with having more good friends. Onset of poly
      victimization in Year 2, in contrast to persistence from Year 1, was associated
      with violent or maltreating families, family problems such as alcohol abuse,
      imprisonment, unemployment and family disruption. Having more older siblings
      acted as both a risk factor and a protective factor for different groups of
      youth. CONCLUSION: Children previously victimized in 1 year are at higher risk of
      continued victimization, and the poly-victims are at particular risk. These
      findings suggest the potential merit of identifying these high-risk children and
      making them priority targets for prevention efforts.

PMID- 17537509
TI  - Reflections on the implications of re-victimization patterns of children and
      youth as clarified by the research of Finkelhor, Ormrod and Turner.

PMID- 17537511
TI  - Cobalt and nickel uptake by rice and accumulation in soil amended with municipal
      solid waste compost.
AB  - Effect of addition of municipal solid waste compost (MSWC) on cobalt (Co) and
      nickel (Ni) contents of submerged rice paddies were studied. A sequential
      extraction method was used to determine the metal (Co and Ni) fractions in MSWC
      and cow dung manure (CDM). Both metals were significantly bound to the organic
      matter and Fe and Mn oxides in MSWC and CDM. Metal content in rice straw was
      higher than in rice grain. Metal bound with Fe and Mn oxides in MSWC and CDM best
      correlated with straw and grain metal followed by water soluble and exchangeable
      fractions. Carbonate, organic matter bound and residual fractions in MSWC and CDM
      did not significantly correlate with rice straw and grain metal. MSWC would be a
      valuable resource for agriculture, but long-term field experiments with MSWC are
      needed to assess by regular monitoring of the metal loads and accumulation in
      soil and plants.

PMID- 17537510
TI  - Microarray analyses reveal distinct roles for Rel proteins in the Drosophila
      immune response.
AB  - The NF-kappaB group of transcription factors play an important role in mediating
      immune responses in organisms as diverse as insects and mammals. The fruit fly
      Drosophila melanogaster express three closely related NF-kappaB-like
      transcription factors: Dorsal, Dif, and Relish. To study their roles in vivo, we
      used microarrays to determine the effect of null mutations in individual Rel
      transcription factors on larval immune gene expression. Of the 188 genes that
      were significantly up-regulated in wild-type larvae upon bacterial challenge,
      overlapping but distinct groups of genes were affected in the Rel mutants. We
      also ectopically expressed Dorsal or Dif and used cDNA microarrays to determine
      the genes that were up-regulated in the presence of these transcription factors.
      This expression was sufficient to drive expression of some immune genes,
      suggesting redundancy in the regulation of these genes. Combining this data, we
      also identified novel genes that may be specific targets of Dif.

PMID- 17537512
TI  - Effects of tebufenozide on some aspects of lake trout (Salvelinus namaycush)
      immune response.
AB  - Tebufenozide is a nonsteroid ecdysone agonist that causes premature and
      incomplete molting in Lepidoptera and is used on crops and in forest spray
      programs. Lake trout (Salvelinus namaycush) were exposed to one pulse of 0.25 ppm
      tebufenozide every 3 days (12 pulses in total). Cell ratios and respiratory burst
      responses of circulating white blood cells (WBCs) as well as head-kidney (HK)
      WBCs were investigated by using cell observation, Nitro-Blue Tetrazolium tests,
      and flow cytometry. Endpoints studied suggest a difference in sensitivity between
      HK and circulating blood cells to tebufenozide and show a stimulation of fish
      cell function and changes in percentages of cell types. Responses are not
      associated with a strong stress response as highlighted by the absence of effect
      on cortisol and blood protein levels. These results and tebufenozide persistence
      in water warrant further studies on pesticide impact on fish immunity when used
      on crops or in forest spray programs near lakes and streams.

PMID- 17537513
TI  - Molecular characterization of avian strains of Pasteurella multocida serogroup
      A:1 based on amplification of repetitive regions by PCR.
AB  - Repetitive extragenic palindromic (REP)-PCR (polymerase chain reaction),
      enterobacterial repetitive intergenic consensus (ERIC)-PCR, and single primer PCR
      assays were employed to characterize 66 strains of Pasteurella multocida
      serogroup A:1 isolated from avian species belonging to different regions of
      India. REP-PCR resulted in amplification of REP sequences from the genome which
      were in the range of approximately 200 to approximately 3000 bp and accounted for
      a total of 54 distinguishing profiles (D=0.99). ERIC-PCR analysis also generated
      amplified products in the range of approximately 200 to approximately 3200 bp
      categorizing strains into a total of 50 different profiles (D=0.98).
      Amplification of repetitive regions using a microsatellite primer (GTG)(5),
      resulted in clear distinctive bands ranging from approximately 200 to
      approximately 2400 bp. Strains were assigned to 43 profiles (D=0.96). No
      correlation could be drawn between genotypic profiles and avian hosts with their
      geographical area of origin. Avian strains of P. multocida serogroup A:1 were
      found to be highly heterogeneous with diverse profiles. REP-PCR was found to be
      highly discriminatory and simple method for differentiation of phenotypically
      similar strains. The present study also indicated that PCR based amplification of
      repetitive regions of P. multocida is a rapid technique with good discrimination
      and could be employed directly for routine typing of field isolates from fowl
      cholera outbreaks.

PMID- 17537514
TI  - Effects of metal binding to mismatched base pairs on DNA-mediated charge
      transfer.
AB  - Photoinduced hole transfer reaction in DNA duplex bearing cytosine-cytosine (CC)
      or thymine-thymine (TT) mismatched base pairs as metal-ion binding sites was
      studied using polyacrylamide gel electrophoresis. Site-specific binding of silver
      (I) ion to a CC mismatched base pair as well as non-specific binding to multiple
      sites of nucleobases in the DNA suppressed hole migration through the sequence.
      In the case of mercury (II) binding to duplex DNA containing single TT mismatch
      at N3 of the pyrimidine rings, little effect on the efficiency of hole transfer
      was observed, which is in accordance with a recent theoretical prediction. On the
      other hand, addition of Hg(II) to duplex containing tandem TT base pairs
      remarkably reduced hole transfer efficiency, although the calculation has
      suggested such binding could form high degree of electronic coupling between the
      hole carrier bases.

PMID- 17537515
TI  - Pulsed laser versus electrical energy for peripheral nerve stimulation.
AB  - Transient optical neural stimulation has previously been shown to elicit highly
      controlled, artifact-free potentials within the nervous system in a non-contact
      fashion without resulting in damage to tissue. This paper presents the
      physiologic validity of elicited nerve and muscle potentials from pulsed laser
      induced stimulation of the peripheral nerve in a comparative study with the
      standard method of electrically evoked potentials. Herein, the fundamental
      physical properties underlying the two techniques are contrasted. Key laser
      parameters for efficient optical stimulation of the peripheral nerve are
      detailed. Strength response curves are shown to be linear for each stimulation
      modality, although fewer axons can be recruited with optically evoked potentials.
      Results compare the relative transient energy requirements for stimulation using
      each technique and demonstrate that optical methods result in highly selective
      functional nerve stimulation. Adjacent stimulation and recording of compound
      nerve potentials in their entirety from optical and electrical stimulation are
      presented, with optical responses shown to be free of any stimulation artifact.
      Thus, use of a pulsed laser exhibits distinct advantages when compared to
      standard electrical means for excitation of muscle potentials in the peripheral
      nerve in the research domain and possibly for clinical diagnostics in the future.

PMID- 17537516
TI  - A portable tactile sensory diagnostic device.
AB  - Current methods for applying multi-site vibratory stimuli to the skin typically
      involve the use of two separate vibrotactile stimulators, which can lead to
      difficulty with positioning of stimuli and in ensuring that stimuli are delivered
      perfectly in phase at the same amplitude and frequency. Previously, we reported a
      two-point stimulator (TPS) that was developed in order to solve the problem of
      delivering two-point stimuli to the skin at variable distances between the sites
      of stimulation. Because of the success of the TPS, we designed and fabricated a
      new stimulator with four significant improvements over our original device.
      First, the device is portable, lightweight and can be used in a variety of non
      laboratory settings. Second, the device consists of two independently controlled
      stimulators which allow delivery of stimuli simultaneously to two distinct skin
      sites with different amplitude, frequency and/or phase. Third, the device
      automatically detects the skin surface and thus allows for much better automated
      control of stimulus delivery. Fourth, the device is designed for rapid
      manufacture and, therefore, can be made readily available to other research (non
      laboratory) settings. To demonstrate the device, a modified Bekesy tracking
      method was used to evaluate the simultaneous amplitude discrimination capacity of
      20 subjects.

PMID- 17537517
TI  - Production, purification and functional validation of human secreted amyloid
      precursor proteins for use as neuropharmacological reagents.
AB  - The secreted fragment of the amyloid precursor protein (sAPPalpha) generated
      following cleavage by alpha-secretase is an important mediator of cell function
      and is both neurotrophic and neuroprotective. HEK 293T cells have been stably
      integrated with a fragment of the APP gene to produce and secrete either
      sAPPalpha, or the alternative cleavage product sAPPbeta. Heparin binding domains
      on the proteins have been utilised to develop a one-step fast-performance-liquid
      chromatography (FPLC) purification of sAPPs from the conditioned media.
      Immunoblotting analyses with a sAPP specific antibody coupled with highly
      sensitive silver staining techniques have validated the expression and
      purification strategy. Functional activity of the purified fragments was
      demonstrated by their ability to protect COS-7 and SH-SY5Y (neuroblastoma) cells
      against the adverse effects of glucose deprivation in a cell viability assay. The
      purified sAPPs also activated the NFkappaB transcription factor in COS-7 cells
      transfected with a luciferase reporter plasmid, with sAPPalpha the more potent
      activator as expected. The simple protocol to produce these mammalian expressed
      proteins will facilitate their use as potential neuropharmacological reagents in
      the elucidation of biochemical pathways modulated by sAPPs, and in the study of
      Alzheimer's disease mechanisms in general.

PMID- 17537518
TI  - Preeclampsia, insulin signalling and immunological dysfunction: a fetal, maternal
      or placental disorder?
AB  - An inappropriate glycogen accumulation in preeclamptic placentas was described as
      secondary to biochemical alterations. Insulin resistance is widely accepted to be
      associated with preeclampsia, although its basis remain unclear. A family of
      putative insulin mediators, namely inositol phosphoglycans, were described to
      exert many insulin-like effects on lipid and glucose metabolism. A definite
      association between the P-type mediator (P-IPG) and preeclampsia was reported,
      being increased in placenta, urine, amniotic fluid and cord blood from human
      preeclamptic pregnancies. A strong link exists between insulin resistance and
      inflammation. Clear features of insulin resistance and systemic inflammatory
      activation were described in preeclampsia. It may be a consequence of the
      immunological dysfunction that occurs in preeclampsia that is temporized during
      sperm exposure and co-habitation which confuses the maternal immune network to
      perceive 'danger'. The over-expression of P-IPG during preeclampsia may be a
      counter-regulatory mechanism to insulin resistance since these molecules mimic
      insulin action. Besides, the lipidic form of P-IPG was reported to be similar to
      endotoxins, and may represent the 'danger signa'. We propose here a novel working
      theory on insulin resistance and preeclampsia.

PMID- 17537519
TI  - Role of sex hormone-binding globulin in the relationship between sex hormones and
      antisocial and aggressive personality in inmates.
AB  - Plasma total testosterone (TT), free bioavailable testosterone (BT), sex hormone
      binding globulin (SHGB), luteinizing hormone (LH), and follicle-stimulating
      hormone (FSH) were analysed in a sample of 89 inmates. Also, the tendency towards
      an Antisocial Personality Disorder (AAPS) and Aggressiveness (based on an index
      containing three scales of the Buss-Durkee Hostility Inventory; BDHI) was
      assessed. Results showed strong correlations between SHBG, total testosterone and
      free bioavailable testosterone. SHBG and total testosterone correlated with
      Aggressiveness (0.39 and 0.29, respectively), though the latter turned out not to
      be significant when SHBG level was controlled. The group with a high probability
      of Antisocial Personality Disorder and the group with high scores in
      Aggressiveness obtained higher SHBG levels. Recidivists and subjects already
      sentenced presented higher concentrations of SHBG. No significant relation was
      found for the free bioavailable testosterone. It is argued that the relationship
      between testosterone and antisocial personality and aggressiveness is mediated by
      the role of SHBG. We conclude that subjects with a disinhibited life-style tend
      to abuse intoxicants affecting the production of SHBG in the liver. This effect
      is observed in healthy subjects and delinquents, but more strongly in the
      population of delinquents.

PMID- 17537520
TI  - Molecular characterization and expression of interferon-gamma of Asian elephant
      (Elephas maximus).
AB  - Tuberculosis (TB) caused by Mycobacterial organisms has emerged as one of the
      major diseases in captive elephants. In vitro Interferon-gamma (IFN-gamma) assay
      is being used as an ancillary test for early detection of TB in domestic and
      captive wild animals. In the present study, basic sequence information and
      immunological cross-reactivity of this major cytokine of Asian elephants were
      explored. At predicted amino acid level, IFN-gamma of Asian elephant showed
      maximum identity to that of horse (73%). Other IFN-gamma amino acid sequences
      that showed high level identity were that of giant panda (72%), dog (71%), nine
      banded armadillo (69%), cattle (63%) and human (62%). IFN-gamma promoter
      sequences of Asian elephant, human, cattle and mouse showed high level
      conservation of the putative transcription factor binding sites, TATA box and
      transcriptional start site. The functionally important human IFN-gamma promoter
      elements, such as AP-2IRE-BE, YY1-gammaIFN-BED, ATFCS and AP-1gammaINF binding
      sites, were absolutely conserved in the corresponding elephant sequence. There
      was only a single nucleotide variation in the other two important elements, NFAT
      gammaINF and IFN-gammaPE, indicating the highly conserved regulation of IFN-gamma
      expression across different species. Phylogenetic analysis based on IFN-gamma
      protein sequences revealed a closer relation of Asian elephants and nine-banded
      armadillo. This shows a closer evolution of these members of Afrotheria and
      Xenarthra, respectively; and supports the previous reports based on mitochondrial
      DNA studies. In Western blot analysis, IFN-gamma of Asian elephant expressed in
      Escherichia coli was detected using an anti-bovine IFN-gamma monoclonal antibody,
      indicating immunological cross-reactivity.

PMID- 17537521
TI  - Further comparisons of assays for detecting MAG IgM autoantibodies.
AB  - Anti-MAG antibodies are commonly found in the sera of patients with demyelinating
      sensorimotor neuropathy and IgM paraproteinemia. Our objective here was to
      compare MAG results obtained by two different laboratories using similar methods
      (Western blot, EIA, IFA). Western blot (WB) employing MAG from monkey was less
      sensitive (72.5%) than myelin IFA (92.5%; monkey nerve) and EIA (97.5%; human
      MAG) when compared to WB using human MAG and is most likely due to methodology
      (not antigen source). EIA detected low titers of MAG IgM antibodies in suspected
      patient sera (negative by other methods) that were also SGPG IgM-positive.
      Patients having low titers by EIA, but negative by WB may have other autoimmune
      neuropathies without demyelination.

PMID- 17537522
TI  - Co-regulated decrease of Neurokinin-1 receptor and Hemokinin-1 gene expression in
      monocytes and macrophages after activation with pro-inflammatory cytokines.
AB  - Hemokinin-1 (HK-1), a potent ligand for the Neurokinin-1 receptor (NK-1) is
      thought to play a role in the immune system. To investigate the regulation of
      this receptor-ligand pair, we examined the effects of pro-inflammatory cytokines
      on their expression in the monocyte/macrophage cell lines Wehi-3 and RAW264.7. We
      demonstrate co-expression of NK-1 and HK-1 mRNA in both lines, as well as
      functional NK-1 receptor protein in Wehi-3 cells. Stimulation with IFN-gamma, IL
      1beta and TNF-alpha markedly decreased NK-1 and HK-1 mRNA as well as NK-1
      receptor protein, which coincided with monocytic differentiation. A co-regulated
      decrease could also be observed in differentiating primary bone marrow
      macrophages, suggesting that this receptor-ligand pair may be controlled by
      cytokine networks and may serve a developmental role in the immune system.

PMID- 17537523
TI  - Proteolytic shedding of the macrophage scavenger receptor CD163 in multiple
      sclerosis.
AB  - The scavenger receptor CD163 is selectively expressed on tissue macrophages and
      human monocytes. CD163 has been implicated to play a role in the clearance of
      hemoglobin and in the regulation of cytokine production by macrophages. Membrane
      CD163 can be cleaved by matrix metalloproteinases (MMP) resulting in soluble
      CD163 (sCD163). In the present report the shedding of CD163 was investigated in
      multiple sclerosis (MS). An upregulation of plasma sCD163 and a down regulation
      of membrane CD163 in MS patients compared to healthy controls was observed. The
      levels of plasma sCD163 correlated with plasma MMP-9 levels in controls, but not
      in MS patients. Moreover, evidence was obtained for CD163-cleaving MMP activity
      in plasma of MS patients. Finally, the increased proteolytic shedding of CD163
      correlated to reduced plasma levels of circulating inflammatory cytokines.
      Collectively, our results provide evidence for proteolytic shedding of CD163 in
      MS and suggest a possible link to cytokine production.

PMID- 17537524
TI  - Clinical application of vestibular evoked myogenic potentials in healthy
      newborns.
AB  - OBJECTIVE: Auditory and vestibular functions have critical importance in infancy
      because they may affect motor and mental development. We aimed to determine the
      normal values of the vestibular evoked myogenic potential (VEMP) parameters to
      provide a reference for further research regarding the early diagnosis of
      vestibular dysfunction in newborns. METHODS: Twenty-four term newborns (12 girls,
      12 boys), with birth weights greater than 2500 g and Apgar scores higher than 7
      at 1 min, were studied. Tympanometry, auditory-evoked brainstem responses,
      transient-evoked otoacoustic emissions, and VEMP recordings were assessed in all
      subjects during fourth week after birth. RESULTS: All newborns passed the
      audiologic evaluation, and biphasic waveforms of the VEMP were obtained in all 48
      tested ears. Mean latencies of p13, n23, and p13-n23 intervals were 13.7+/-1.1,
      20.5+/-1.6, and 7.1+/-2.1 ms, respectively. The mean amplitude value was 22.6+/
      18.4 microV. There were no significant differences in latency values or
      amplitudes with regard to sex or side of ear tested in newborns. CONCLUSIONS:
      VEMP may easily be used for early evaluation of vestibular dysfunction in
      newborns. Because results may differ owing to test techniques and age, every
      laboratory should have its own normal values.

PMID- 17537525
TI  - Systemic and central amygdala injections of the mGluR2/3 agonist LY379268
      attenuate the expression of incubation of sucrose craving in rats.
AB  - We previously reported that systemic or central amygdala injections of the
      mGluR(2/3) agonist LY379268 (which decreases glutamate release) prevented
      enhanced cue-induced cocaine seeking in extinction tests after prolonged
      withdrawal (incubation of cocaine craving). Here, we report that systemic and
      central amygdala injections of LY379268 also prevented the enhanced cue-induced
      sucrose seeking in extinction tests after prolonged sucrose-free period
      (incubation of sucrose craving). These findings suggest that central amygdala
      glutamate plays an important role in the incubation of reward craving after
      withdrawal from both drug and non-drug rewards.

PMID- 17537527
TI  - Cloning and expression of a biologically active Anisakis simplex allergen Ani s 1
      in the yeast Pichia pastoris.

PMID- 17537526
TI  - Social function in boys with cleft lip and palate: relationship to ventral
      frontal cortex morphology.
AB  - Isolated clefts of the lip and/or palate (ICLP) are developmental craniofacial
      abnormalities that have consistently been linked to increased social inhibition
      or shyness. Two explanations have been proposed: (1) psychosocial factors related
      to differences in facial appearance may lead to low self-concept and subsequent
      shyness, or (2) abnormal development of brain structures involved in social
      function, such as the ventral frontal cortex (VFC), may underlie the difference.
      To investigate these two possibilities this study was designed to evaluate
      measures of social function in relation to measures of self-concept and VFC
      morphology. Subjects included 30 boys (age 7-12) with ICLP and a comparison group
      of 43 boys without cleft in the same age category. Social function and self
      concept were assessed using questionnaires with standardized scoring filled out
      by subjects and one of their parents. The cortical volume and surface area of the
      VFC, composed of the orbitofrontal cortex (OFC) and straight gyrus (SG), were
      evaluated using structural magnetic resonance imaging. The ICLP subjects had
      significantly impaired social function relative to the comparison group. No
      difference in self-concept was identified. VFC morphology revealed significant
      differences between groups, particularly decreased volume and surface area in the
      left SG of the ICLP group. Moreover, abnormal VFC measures were correlated with
      social dysfunction but measures of self-concept were not. These results are
      consistent with the possibility that aberrant VFC development may partially
      underlie social dysfunction in boys with ICLP.

PMID- 17537528
TI  - Are Caenorhabditis elegans receptors useful targets for drug discovery:
      pharmacological comparison of tyramine receptors with high identity from C.
      elegans (TYRA-2) and Brugia malayi (Bm4).
AB  - The biogenic amine, tyramine (TA), modulates a number of key processes in
      nematodes and a number of TA-specific receptors have been identified. In the
      present study, we have identified a putative TA receptor (Bm4) in the recently
      completed Brugia malayi genome and compared its pharmacology to its putative
      Caenorhabditis elegans orthologue, TYRA-2, under identical expression and assay
      conditions. TYRA-2 and Bm4 are the most closely related C. elegans and B. malayi
      BA receptors and differ by only 14aa in the TM regions directly involved in
      ligand binding. Membranes from HEK-293 cells stably expressing Bm4 exhibited
      specific, saturable, high affinity, [(3)H]LSD and [(3)H]TA binding with K(d)s of
      18.1+/-0.93 and 15.1+/-0.2 nM, respectively. More importantly, both TYRA-2 and
      Bm4 TA exhibited similar rank orders of potencies for a number of potential
      tyraminergic ligands. However, some significant differences were noted. For
      example, chloropromazine exhibited an order of magnitude higher affinity for Bm4
      than TYRA-2 (pK(i)s of 7.6+/-0.2 and 6.49+/-0.1, respectively). In contrast, TYRA
      2 had significantly higher affinity for phentolamine than Bm4. These results
      highlight the utility of the nearly completed B. malayi genome and the importance
      of using receptors from individual parasitic nematodes for drug discovery.

PMID- 17537529
TI  - Characterization of Entamoeba histolytica alpha-actinin2.
AB  - We have cloned and characterized a second alpha-actinin isoform in Entamoeba
      histolytica. This protein, alpha-actinin2, has a N-terminal actin-binding domain,
      a C-terminal calcium-binding domain and an intervening rod domain containing two
      spectrin repeats. The protein binds and cross-links actin filaments in a calcium
      dependent manner. Therefore alpha-actinin2 is a genuine alpha-actinin except for
      the shorter rod domain compared to the rod domain of isoforms of higher
      organisms. A alpha-actinin-like protein has previous been implicated in the
      adherence to the host cell and infection. It is therefore possible that alpha
      actinin2 is involved in mechanism of infection, and in particular in
      reorganisation of the parasite's cytoskeleton that follows on adherence. E.
      histolytica alpha-actinin2 represents one of the first members of the spectrin
      superfamily where well defined spectrin repeats are found. The isolation and
      characterization of this second alpha-actinin isoform is valuable not only into
      the study of E. histolytica infection mechanisms, but also for understanding the
      evolution processes of the spectrin superfamily.

PMID- 17537530
TI  - Effect of ppMCH derived peptides on PBMC proliferation and cytokine expression.
AB  - The mRNA encoding prepro-Melanin concentrating hormone (ppMCH) is mainly
      expressed in the central nervous system but has also been detected at lower
      amount in many peripheral tissues including spleen and thymus. At the peptide
      level however, several forms of the precursor can be detected in these tissues
      and are sometimes expressed at similar levels compared to brain. In the present
      work, we have studied the in vitro action of a wide range of concentration (1 nM
      to 1 microM) of the different peptides encoded by ppMCH i.e. neuropeptide glycine
      glutamic acid (NGE), neuropeptide glutamic acid-isoleucine (NEI), Melanin
      concentrating hormone (MCH) and the dipeptide NEI-MCH on peripheral blood
      mononuclear cells (PBMC) proliferation and cytokine production following anti-CD3
      stimulation. Among them only MCH decreased PBMC proliferation with a maximal
      effect of 35% at 100 nM. Moreover as demonstrated by using ELISA, MCH
      significantly decreases IL-2 production by 25% but not IL-4, INF-gamma or TNF
      alpha expression. Interestingly, exogenous IL-2 decreases significantly MCH
      mediated inhibition, suggesting that it is an important downstream mediator of
      MCH action. Finally, we showed that after 7 to 9 days of incubation, MCH also
      inhibits proliferation of non-stimulated PBMC. Altogether, these data demonstrate
      that fully mature MCH modulates proliferation of anti-CD3 stimulated PBMC
      partially through regulation of IL-2 production.

PMID- 17537531
TI  - Multi-slice cardiac computed tomography reveals anomalous origin of the right
      coronary artery between the great arteries.
AB  - We report a case of a 72-year-old man whose multi-slice cardiac computed
      tomography revealed an anomalous origin of the right coronary artery between the
      great arteries.

PMID- 17537532
TI  - Evaluation of microalbuminuria after non-ionic radiocontrast medium exposure in
      patients undergoing coronary angiography.
AB  - Transient and massive glomerular proteinuria, previously reported as one of the
      nephrotoxic reactions after ionic radiocontrast medium (RCM) exposure, is rarely
      observed in patients since the introduction of non-ionic RCM. However, whether
      the very low-range microalbuminuria might be encountered after non-ionic RCM
      exposure remains unknown. In this study we sought to investigate the effects of
      non-ionic RCM (Ultravist 370) exposure on the presence of microalbuminuria,
      defined as urine albumin-to-creatinine ratio (UACR) >30 mg/g, by a turbidmetric
      method in total of 64 patients (17 female, mean age 58+/-12 years) undergoing
      coronary angiography. The results showed that after non-ionic RCM (mean volume
      103+/-57 ml) exposure, no significant differences were found in urinary albumin
      concentration or UACR; however, urinary creatinine was significantly reduced from
      116+/-62 to 69+/-43 mg/dl (p<0.001). Changes in the presence of microalbuminuria
      before and after procedure were also not significant (p=0.891, McNemar test). In
      conclusion, non-ionic RCM exposure during CAG had negligible effect on the
      excretion of urinary albumin even within the detection range of microalbuminuria.

PMID- 17537533
TI  - Pericarditis causing congestive heart failure as an initial manifestation of
      systemic lupus erythematosus.
AB  - Pericarditis is a common complication in systemic lupus erythematosus (SLE)
      patients, however, that causing congestive heart failure (CHF) is a rare initial
      manifestation of SLE. We treated a patient whose initial manifestation of SLE was
      pericardial effusion causing CHF, which improved following prednisolone therapy
      that led to a dramatic decrease in pericardial effusion and improvement in left
      ventricular diastolic dysfunction as shown in Doppler echocardiography findings.
      Further, the plasma brain natriuretic peptide level became normalized.

PMID- 17537534
TI  - Psychophysiology of anger: introduction to the special issue.

PMID- 17537535
TI  - A predictive model for the influence of food components on survival of Listeria
      monocytogenes LM 54004 under high hydrostatic pressure and mild heat conditions.
AB  - The combination of high hydrostatic pressure with mild temperature was explored
      to achieve a predictive model of microbial inactivation in food matrix
      processing. The pressure processing conditions were fixed at 448 MPa for 11 min
      at the treatment temperature of 41 degrees C, which have been determined as the
      optimum processing conditions considering six log-cycle reductions of Listeria
      monocytogenes. Based on the results, response surface methodology (RSM) was
      performed in the present work, the influence of food components like soybean
      protein (0-5.00%), sucrose (0.25-13.25%), bean oil (0-10.00%), and pH (4-10) of
      the food matrix on survival of L. monocytogenes by high pressure and mild heat
      was studied, and a quadratic predictive model for the influence of food
      components and pH of food matrix on L. monocytogenes reduction by high pressure
      and mild heat was built with RSM accurately. The experimental results showed that
      the efficiency of L. monocytogenes reduction in milk buffer and food matrix
      designed in the present work, under the HPP treatment process parameters
      described above, were different. The soybean protein (P=0.0086), sucrose
      (P<0.0001), and pH (P=0.0136) significantly affected reduction of L.
      monocytogenes, but the effect of bean oil on reduction of L. monocytogenes was
      not significant (P=0.1028). The predictive model is significant since the level
      of significance was P<0.0001 and the calculated F value (11.53) is much greater
      than the tabulated F value (F(0.01 (14, 5))=9.77). Moreover, the adequacy of the
      predictive model equation for predicting the level of L. monocytogenes reduction
      was verified effectively by the validation data.

PMID- 17537536
TI  - Molecular epidemiology of rabies in bat-eared foxes (Otocyon megalotis) in South
      Africa.
AB  - A panel of 124 rabies viruses from wildlife host species (principally the bat
      eared fox, Otocyon megalotis) and domestic carnivore species were collected
      between 1980 and 2005 from a region of South Africa associated with endemic bat
      eared fox rabies. We have studied the molecular epidemiology of bat-eared fox
      rabies by virtue of nucleotide sequence analyses of PCR amplicons specific to the
      variable G-L intergenic region as well as the conserved nucleoprotein gene of
      each of the rabies viruses in this South African panel. Although it was
      demonstrated that all of these viruses were very closely related, they could be
      segregated into two major phylogenetic groups. The data presented in this paper
      complement antigenic and surveillance data on rabies in this host species in
      South Africa. Most importantly our data support a hypothesis that the bat-eared
      fox independently maintains rabies cycles in specific geographical loci. This is
      the first molecular epidemiological investigation describing rabies transmission
      dynamics in this wildlife carnivore host species in South Africa.

PMID- 17537537
TI  - Interactions between U-937 human macrophages and poly(propyleneimine) dendrimers.
AB  - Interest in using poly(propyleneimine) (PPI) dendrimers for biomedical
      applications is increasing. Before using PPI dendrimers in vivo, their
      interactions with macrophages must be fully understood because they are primarily
      removed from circulation by the macrophages of the mononuclear phagocyte system.
      However, few investigators have studied in detail the intracellular responses
      that cationic dendrimers induce in macrophages. Here we examined the
      intracellular responses-reactive oxygen species (ROS) content, mitochondria
      membrane potential, cell size and complexity, and cell cycle profiles-in U-937
      human macrophages treated with poly(propyleneimine) dendrimers generation 2 (DAB
      2.0) and 3 (DAB 3.0). Our study focused on the concentration ranges within which
      cell viability was greater than 90% after PPI dendrimers had been incubated for
      16 h. For spontaneous ROS generation, DAB 2.0 did not consistently generate
      hydrogen peroxide production with increasing dosages over the entire culture
      period while it was capable of generating superoxide content except during the 12
      h of incubation. In contrast, DAB 3.0 did not induce any hydrogen peroxide and
      superoxide production except for an abrupt increase of superoxide content at 60
      microg/mL after 6 h of incubation. Our results showed that ROS responses in
      macrophages were strongly influenced by the nature of the dendrimer surface.
      Except at 3 h, DAB 2.0 increased mitochondrial membrane potential for every dose
      and culture period. In contrast, DAB 3.0 caused a significant fluctuation in
      mitochondrial membrane potential only at 6 h, compared with other incubation
      times. Exposing macrophages to PPI dendrimers caused dramatic and significant
      changes in macrophage cell size and complexity, and DAB 3.0 caused greater
      changes than DAB 2.0 did. For incubation times longer than 1 h, propidium iodide
      staining showed that cells treated with DAB 2.0 and 3.0 had a higher subG1 phase
      (indicative of apoptosis) than did untreated cells. PPI dendrimers induced
      different activated patterns in ROS generation and changes of mitochondrial
      membrane potential than did other carriers such as cationic liposomes and
      polyalkylcyanoacrylate. The nature of interactions between macrophages and PPI
      dendrimers is crucial for the design of safer and more effective delivery systems
      for macrophages. Our findings provide a novel insight into the cytotoxic effects
      at the molecular level that dendrimers cause in macrophages.

PMID- 17537538
TI  - Detection of unsuspected distant metastases and/or regional nodes by FDG-PET
      [corrected] scan in apparent limited-disease small-cell lung cancer.
AB  - We retrospectively investigated the clinical usefulness of fluorodeoxyglucose
      positron emission tomography (FDG-PET) for evaluation of patients with limited
      disease small-cell lung cancer (LD-SCLC) diagnosed by conventional staging
      procedures. Sixty-three patients received whole body FDG-PET scans after routine
      initial staging procedures. The findings of FDG-PET scans suggesting extensive
      stage disease were confirmed by other imaging tests or by the patient's clinical
      course. FDG-PET scan findings indicated distant metastases in 6 of 63 patients.
      Metastatic disease was confirmed in five of these six patients (8%, 95%
      confidence interval: 3-18%). FDG-PET scan also detected regional lymph node
      metastases even in nine patients (14%) in whom computed tomography images had
      been negative, including contralateral lymph node metastasis in three patients.
      FDG-PET scan detected additional lesions in patients diagnosed as having LD-SCLC
      by conventional staging procedures. The therapeutic strategies were changed in 8%
      of patients based on the results of FDG-PET. FDG-PET scan is recommended as an
      initial staging tool for patients with this disease.

PMID- 17537539
TI  - Effect of short-duration physical activity and ventilation threshold on
      subjective appetite and short-term energy intake in boys.
AB  - The purpose of this investigation was twofold: (1) to examine the role of low- to
      moderate-intensity, short-duration physical activity on subjective appetite and
      (2) to identify the role of and associations between ventilation threshold (VeT)
      and energy intake at a pizza lunch 30 min after glucose and whey protein drinks
      in normal weight boys. In 14 boys (age: 12.5+/-0.4 years) subjective appetite was
      measured before and after a 12 min walking protocol designed to determine
      physical fitness based on the VeT. On a separate occasion food intake (FI) and
      subjective appetite were measured in response to sweetened preloads of either a
      SPLENDA Sucralose control, glucose or whey protein made up to 250 ml with water,
      given in random order to each boy, 2h after a standardized breakfast. Subjective
      average appetite and prospective food consumption scores increased after physical
      activity. VeT was positively associated with FI at a pizza lunch consumed 30 min
      after glucose and whey protein drinks. Glucose and whey protein reduced FI
      similarly at lunch compared with control. In conclusion, appetite is increased by
      low- to moderate-intensity, short-duration physical activity and FI following
      glucose and protein preloads is positively associated with fitness levels in
      boys.

PMID- 17537540
TI  - The convenience food market in Great Britain: convenience food lifestyle (CFL)
      segments.
AB  - Convenience foods enable the consumer to save time and effort in food activities,
      related to shopping, meal preparation and cooking, consumption and post-meal
      activities. The objective of this paper is to report on the attitudes and
      reported behaviour of food consumers in Great Britain based on a review of their
      convenience food lifestyle (CFLs). The paper also reports the development and
      application of a segmentation technique that can supply information on consumer
      attitudes towards convenience foods. The convenience food market in Great Britain
      is examined and the key drivers of growth in this market are highlighted. A
      survey was applied to a nationally representative sample of 1000 consumers
      (defined as the persons primarily responsible for food shopping and cooking in
      the household) in Great Britain in 2002. Segmentation analysis, based on the
      identification of 20 convenience lifestyle factors, identified four CFL segments
      of consumers: the 'food connoisseurs' (26%), the 'home meal preparers' (25%), the
      'kitchen evaders' (16%) and the 'convenience-seeking grazers' (33%). In
      particular, the 'kitchen evaders' and the 'convenience-seeking grazers' are
      identified as convenience-seeking segments. Implications for food producers, in
      particular, convenience food manufacturers are discussed. The study provides an
      understanding of the lifestyles of food consumers in Great Britain, and provides
      food manufacturers with an insight into what motivates individuals to purchase
      convenience foods.

PMID- 17537541
TI  - Bioactive analogues and drug delivery systems of vasoactive intestinal peptide
      (VIP) for the treatment of asthma/COPD.
AB  - Vasoactive intestinal peptide (VIP) is one of the major peptide transmitters in
      the central and peripheral nervous systems, being involved in a wide range of
      biological functions. In an airway system where VIP-immunoreactive nerve fibers
      are present, VIP acts as neurotransmitter or neuromodulator of the inhibitory non
      adrenergic and non-cholinergic airway nervous system and influences many aspects
      of pulmonary biology. A clinical application of VIP has been believed to offer
      potential benefits in the treatment of chronic inflammatory lung diseases such as
      asthma and chronic obstructive pulmonary disease (COPD), however, its clinical
      application has been limited in the past for a number of reasons, including its
      extremely short plasma half-life after intravenous administration and difficulty
      in administration routes. The development of long-acting VIP analogues, in
      combination with appropriate drug delivery systems, may provide clinically useful
      agents for the treatment of asthma/COPD. In this review, development of
      efficacious VIP derivatives, drug delivery systems designed for VIPs and the
      potential application for asthma/COPD are discussed. We also include original
      data from our chemical modification experiments and formulation studies, which
      led to successful development of [R(15, 20, 21), L(17)]-VIP-GRR (IK312532), a
      potent VIP analogue, and a VIPs-based dry powder inhaler system.

PMID- 17537542
TI  - The lipopeptides Pal-Lys-Lys-NH(2) and Pal-Lys-Lys soaking alone and in
      combination with intraperitoneal vancomycin prevent vascular graft biofilm in a
      subcutaneous rat pouch model of staphylococcal infection.
AB  - Staphylococcal infections are often associated with the use of implantable
      medical devices. Such infections are difficult to treat because of biofilm
      resistance to antibiotics and are common causes of morbidity and mortality. Graft
      infections were established in the back subcutaneous tissue of adult male Wistar
      rats by implantation of Dacron prostheses followed by topical inoculation with
      2x10(7) colony-forming units of bacterial strains. The study included a control
      group, a contaminated group that did not receive any antibiotic prophylaxis and
      five contaminated groups that received intraperitoneal vancomycin, Pal-Lys-Lys
      NH(2) and Pal-Lys-Lys-soacked graft, and vancomycin plus Pal-Lys-Lys-NH(2) or Pal
      Lys-Lys-soacked graft, respectively. The infection was evaluated by using
      sonication and quantitative agar culture. Moreover, an in vitro antibiotic
      susceptibility assay for Staphylococcus aureus biofilms was performed to
      elucidate the same activity. When tested alone, vancomycin and lipopeptides
      showed comparable efficacies. All combinations showed efficacies significantly
      higher than that of each single compound. Vancomycin combined to Pal-Lys-Lys
      NH(2) exerted the strongest anti-staphylococcal efficacies. The in vitro studies
      showed, that MIC and MBC values for vancomycin were lower in presence of
      lipopeptides. They reduce the bacterial load and to enhance the effect of
      vancomycin in the prevention of vascular graft staphylococcal infections.

PMID- 17537543
TI  - Neuropeptide precursors in Tribolium castaneum.
AB  - Neuropeptides and neurohormones are among the more diverse and functionally
      important classes of cell-to-cell signaling molecules involved in animal
      development and behavior. Less is known about the hormones and neuropeptides of
      the red flour beetle, Tribolium castaneum, than many other insects. However, the
      genomic information becoming available from this organism presents an opportunity
      to identify multiple neuropeptide and hormone genes, and hence their associated
      protein precursors. Using similarity-based prediction, we report new
      neuropeptides and hormone precursors from T. castaneum, bringing the number of
      annotated precursors to 37. We identified one prohormone (SVDPIDGDLIG-containing)
      having little similarity to other insect prohormones. The conversion of the
      protein precursors into bioactive peptides requires a suite of processing enzymes
      and a number of enzymatic steps; using the web-based NeuroPred application and
      similarity-based bioinformatics approaches, we predict 132 likely peptides that
      may result from the enzymatic processing of these gene products.

PMID- 17537544
TI  - Neonatal oxytocin treatment modulates oxytocin receptor, atrial natriuretic
      peptide, nitric oxide synthase and estrogen receptor mRNAs expression in rat
      heart.
AB  - Oxytocin (OT) has been implicated in reproductive functions, induction of
      maternal behavior as well as endocrine and neuroendocrine regulation of the
      cardiovascular system. Here we demonstrate that neonatal manipulation of OT can
      modulate the mRNAs expression for OT receptor (OTR), atrial natriuretic peptide
      (ANP), endothelial nitric oxide synthase (eNOS) and estrogen receptor alpha
      (ERalpha) in the heart. On the first day of postnatal life, female and male rats
      were randomly assigned to receive one of the following treatments: (a) 50microl
      i.p. injection of 7microg OT; (b) 0.7microg of OT antagonist (OTA); or (c)
      isotonic saline (SAL). Hearts were collected either on postnatal day 1 or day 21
      (D1 or D21) and the mRNAs expression of OTR, ANP, inducible NOS (iNOS), eNOS,
      ERalpha and estrogen receptor beta (ERbeta) were compared by age, treatment, and
      sex utilizing real time PCR. OT treatment significantly increased heart OTR, ANP
      and eNOS mRNAs expression on D1 in both males and females, ERalpha increased only
      in females. While there were significant changes in the relative expression of
      all types of mRNA between D1 and D21, there were no significant treatment effects
      observed in D21 animals. OTA treatment significantly decreased basal ANP and eNOS
      mRNAs expression on D1 in both sexes. The results indicate that during the early
      postnatal period OT can have an immediate effect on the expression OTR, ANP,
      eNOS, and ERalpha mRNAs and that these effects are mitigated by D21. Also with
      the exception of ERalpha mRNA, the effects are the same in both sexes.

PMID- 17537545
TI  - Ethnic differences in adrenocorticotropic hormone, cortisol and corticotropin
      releasing hormone during pregnancy.
AB  - Significant ethnic disparities exist in reproductive outcomes. A potential
      contributing factor may be the functioning of the hypothalamic-pituitary-adrenal
      (HPA) axis and placenta during pregnancy. In the present study, levels of
      cortisol, ACTH and CRH were determined longitudinally from the plasma of 310
      African American, Hispanic and non-Hispanic White women at 18-20, 24-26 and 30-32
      weeks' gestation. During pregnancy, African American women exhibited lower levels
      of cortisol than non-Hispanic women and higher levels of ACTH than Hispanic
      women. The trajectory of CRH increase also differed by ethnicity, with African
      Americans exhibiting the lowest levels both early and late in pregnancy. Higher
      levels of cortisol at 18-20 weeks were associated with higher levels of CRH at 30
      32 weeks among the African American and Hispanic women, but not among non
      Hispanic women. Ethnic differences persisted when adjusting statistically for
      sociodemographic and biomedical factors. The findings are consistent with the
      possibility that ethnic disparities in adverse birth outcomes may be due, in
      part, to differences in HPA axis and placental function.

PMID- 17537547
TI  - Homocysteine induces tau phosphorylation by inactivating protein phosphatase 2A
      in rat hippocampus.
AB  - Hyperhomocysteinemia increases the risk of Alzheimer's disease (AD), but the
      mechanism is elusive. Here, we found that high plasma homocysteine induced by
      vena caudalis injection for 2 weeks could induce AD-like tau hyperphosphorylation
      at multiple sites in rat brain hippocampus. Homocysteine inhibited the activity
      of protein phosphatase 2A (PP2A) with a simultaneously increased Leu(309)
      demethylation and Tyr(307)-phosphorylation of PP2A catalytic subunit (PP2A(C)).
      PP2A(C) Leu(309)-demethylation was positively correlated with its Tyr(307)
      phosphorylation; and the abnormally modified PP2A(C) was incompetent in binding
      to its regulatory subunit (PP2A(B)). Homocysteine also activated methylesterase
      which stimulates demethylation of PP2A(C). In hippocampal slices of the
      homocysteine injected-rats and of the AD patients, the demethylated but not the
      methylated PP2A(C) was co-localized with the hyperphosphorylated tau. A
      simultaneous supplement of folate and vitamin B12 restored partially the plasma
      homocysteine level and thus significantly antagonized the homocysteine-induced
      tau hyperphosphorylation and as well as PP2A inactivation and the activity
      related modifications of PP2A(C). These results suggest that homocysteine may be
      an upstream effector to induce AD-like tau hyperphosphorylation through
      inactivating PP2A.

PMID- 17537546
TI  - Synuclein activates microglia in a model of Parkinson's disease.
AB  - Parkinson's disease (PD) is the most common neurodegenerative movement disorder
      afflicting >500,000 patients in the United States alone. This age-related
      progressive disorder is typified by invariant loss of dopaminergic substantia
      nigra neurons (DAN), dystrophic neurites, the presence of alpha-synuclein (SYN)
      positive intracytoplasmic inclusions (Lewy bodies) in the remaining DAN, and
      activated microglia. As such, microglial activation and resultant increase in
      proinflammatory molecules have moved to the forefront of PD research as a
      potential pathobiologic mechanism of disease. Herein, we present data
      demonstrating early microglial activation in mice that over-express wild-type
      SYN, the release of SYN from a SYN overexpressing MN9D cell line, and dose
      dependent SYN-mediated activation of primary microglial cultures with consequent
      increases in proinflammatory molecules. Furthermore, we provide evidence that the
      CD36 scavenger receptor and downstream kinases are involved in SYN-mediated
      microglial activation. Together, our data suggest an early role for SYN and
      inflammation in PD pathogenesis.

PMID- 17537548
TI  - Age-related changes in cerebellar phosphatase-1 reduce Na,K-ATPase activity.
AB  - We evaluated whether changes in protein content and activity of PP-1 and PP-2A
      were the mechanism underneath the basal age-related reduction in alpha(2/3)-Na,K
      ATPase activity in rats cerebella and whether this occurred through the cyclic
      GMP-PKG pathway. PP1 activity, but not its expression, increased with age,
      whereas PP-2 was not changed. The activity of alpha(2/3)-Na,K-ATPase varied with
      age, and there was a negative association between the PP-1 and alpha(2/3)-Na,K
      ATPase activities. In young rats, the inhibition of PP-1 and PP-2A by okadaic
      acid (OA) increased in a dose-dependent manner alpha(1)- and alpha(2/3)-Na,K
      ATPase, but had no effect on Mg-ATPase activity. A direct stimulation of PKG with
      8-Br-cyclic GMP did not surmount the effect of OA. This analogue of cyclic GMP
      inhibited PP-1 activity only, indicating that at least part of the increase in
      alpha(1)- and alpha(2/3)-Na,K-ATPase activity induced by OA was mediated by the
      cyclic GMP-PKG-PP-1 cascade. Taking into account that PP1 inhibition increased
      alpha(2/3)-Na,K-ATPase activity, we propose that an age-related increase in PP-1
      activity due to a decrease in cyclic GMP-PKG modulation plays a role for the age
      related reduction of alpha(2/3)-Na,K-ATPase activity in rat cerebellum.

PMID- 17537549
TI  - [Case-control study evaluating the incidence of hyperhomocysteinemia in cancer
      patients in an internal medicine department].
AB  - PURPOSE: Cancer is a cause of venous thromboembolism. However, the
      physiopathology remains unknown. Hyperhomocysteinemia could be a promoting
      factor. METHOD: We built a case-control study of 65 patients followed for 2 years
      to compare levels of homocysteinemie in cancer bearing patients with that in
      matched cancer free control patients. RESULTS: Fifty per cent of cancer bearing
      patients had significantly increased blood serum levels of homocysteine
      (P=0.006). This increase did not correlate with any deficiency in blood serum
      levels of folate or vitamin B12. CONCLUSION: High levels of homocysteinemie could
      be linked to tumor proliferation.

PMID- 17537550
TI  - [A persistent dysphagia].

PMID- 17537551
TI  - Robust take following exposure to vaccinia virus: case definition and guidelines
      of data collection, analysis, and presentation of immunization safety data.

PMID- 17537552
TI  - Generalized vaccinia as an adverse event following exposure to vaccinia virus:
      case definition and guidelines for data collection, analysis, and presentation of
      immunization safety data.

PMID- 17537553
TI  - Inadvertent inoculation as an adverse event following exposure to vaccinia virus:
      case definition and guidelines for data collection, analysis, and presentation of
      immunization safety data.

PMID- 17537554
TI  - Hypotonic-hyporesponsive episode (HHE) as an adverse event following immunization
      in early childhood: case definition and guidelines for data collection, analysis,
      and presentation.

PMID- 17537555
TI  - Production of clinical-grade plasmid DNA for human Phase I clinical trials and
      large animal clinical studies.
AB  - The use of plasmid DNA as vaccines for the treatment of cancer and infectious
      diseases is on the rise. In order to facilitate the manufacture of clinical-grade
      plasmid DNA for Phase I clinical trials, we developed a process whereby >200 mg
      plasmid could be produced in a single production run under Good Manufacturing
      Practices. A dedicated cleanroom (Class 10,000 with Class 100 biosafety cabinet)
      is utilized for production of the bacterial cell bank, fermentation,
      harvest/lysis of the biomass, and downstream purification. Fermentation requires
      three 16-18 h runs (approximately 12 L each) in shaker-flasks, yielding
      approximately 60 g bacterial paste following batch centrifugation. The biomass is
      alkaline-lysed, pooled, and the resulting flocculent precipitate is separated by
      a novel vacuum step, followed by depth-filtration. Downstream processing includes
      anion-exchange chromatography, utilizing Qiagen silica-based resin, and
      precipitation with isopropanol. Following precipitation, the DNA is harvested by
      centrifugation, dried, formulated, and sterile-filtered using a Sartorius
      Sartobran 150 filter prior to Final-Filling. All processing steps utilize
      sterilized, single-use components. This process results in a product manufactured
      according to regulatory guidelines. The plasmid DNA is sterile with >or=95%
      supercoiled DNA, an A260/A280 ratio>or=1.9, undetectable or extremely low
      residual endotoxin, RNA, genomic DNA, protein, and antibiotic. Residual solvent
      levels are negligible. The product yields the predicted profile upon restriction
      enzyme digestion, is biologically active upon transfection and remains stable for
      several years at -20 degrees C. We have therefore developed a reproducible and
      cost effective process to manufacture clinical-grade plasmid DNA. This process
      can be adapted by other academic centers for human or large animal clinical
      trials.

PMID- 17537556
TI  - Prospective study of the incidence of serious posterior maxillary haemorrhage
      during a tuberosity osteotomy in low level Le Fort I operations.
AB  - The incidence of serious haemorrhage in Le Fort I osteotomy is low and attempts
      to reduce this further have led to the development of various techniques to
      minimise vascular injury. This includes the tuberosity osteotomy and was
      published over two decades ago. This technique has not been widely adopted as
      shown by a recent UK survey of consultants, which suggested that only 12 (7%) of
      the 175 surgeons who responded, routinely use tuberosity osteotomy in non-cleft
      low level Le Fort I procedures. The aim of the study was to examine prospectively
      the incidence of serious haemorrhage from the posterior maxilla during tuberosity
      osteotomy. We report 35 consecutive patients who have had no operative or
      postoperative vascular complications.

PMID- 17537557
TI  - Central mucoepidermoid carcinoma: report of 2 cases.
AB  - Central mucoepidermoid carcinoma is a rare mandibular neoplasm. The objective of
      this paper was to report two cases.

PMID- 17537559
TI  - Patent nasopalatine duct: a diagnostic pitfall.
AB  - We describe a patient in whom the combination of excessive air in the maxillary
      sinus and the presence of a patent nasopalatine duct led to misdiagnosis and
      subsequent treatment of a non-existent oroantral perforation. When a radiograph
      indicates that antral involvement during removal of a maxillary molar is
      unlikely, and yet a routine postoperative nose-blowing test contradicts this, the
      possible presence of a pre-existent oronasal communication such as a patent
      nasopalatine duct should be considered.

PMID- 17537558
TI  - Prospective study of the septocutaneous radial free flap and suprafascial donor
      site.
AB  - This is a prospective study of 121 consecutive radial septocutaneous flaps
      harvested by one surgeon. There were 117 successful flaps (97%). The incidence of
      early return to theatre for potential problems with the flap or the neck wound
      was 12/121 (10%) and the flap salvage rate was 3/7 (43%). The incidence of three
      early wound healing complications at the suprafascial donor site were: loss of
      the skin graft (4%), tendon exposure (3%) and delayed healing (4%). A full
      thickness skin graft, usually from the inner upper arm, was used to repair three
      quarters of donor site defects. The median time to healing was significantly
      longer for partial thickness grafts (14 days compared with 10 days, p<0.001). The
      degree of contraction of the skin graft used to repair the radial defect was
      significantly less for full thickness than partial thickness grafts (median -21%
      compared with -33%, p=0.01). There was more relative contraction with larger
      grafts (p<0.001) and in older patients (p=0.01). The septocutaneous radial flap
      is reliable. The early morbidity at the suprafascial donor site is relatively low
      in comparison to that reported at the subfascial donor site.

PMID- 17537560
TI  - Co-occurence of blepharospasm, tourettism and obsessive-compulsive symptoms
      during lamotrigine treatment.

PMID- 17537561
TI  - Catatonia and consultation-liaison psychiatry study of 12 cases.
AB  - Nowadays, catatonia is no more considered as a subtype of schizophrenia.
      Catatonia seems more frequently associated to mood disorders as well as general
      medical conditions. It is sometimes difficult to associate formally a medical
      etiology to this syndrome. But we found, in the literature, three groups of
      associated general medical conditions: neurological disorders, drug induced and
      toxic induced conditions, metabolic conditions. We present a prospective study of
      12 clinical cases of catatonia due to general medical conditions we realized in
      the Consultation-Liaison Psychiatry Department of the University Hospital of
      LILLE (France) during a period of 5 months. We find coherent data with the
      literature. However, our results suggest that if medical conditions precipitate
      the catatonia syndrome, they are rarely its only etiology. We think that if
      somatic factors are co-morbid with psychiatric conditions they do not necessarily
      predominate as the target of treatment. The treatment of the catatonia must be a
      priority and remain symptomatic, to allow in parallel the specific treatment for
      the somatic disorder or the psychiatric disorder.

PMID- 17537562
TI  - Effects of fluoride on the expression of NCAM, oxidative stress, and apoptosis in
      primary cultured hippocampal neurons.
AB  - The mechanisms underlying the neurotoxicity of endemic fluorosis still remain
      unknown. To investigate the expression level of neural cell adhesion molecules
      (NCAM), oxidative stress, and apoptosis induced by fluoride, the primary rat
      hippocampal neurons were incubated with 20, 40, and 80 mg/l sodium fluoride for
      24 h in vitro. The results showed that the cell survival rate in the 80 mg/l
      fluoride-treated group was significantly lower than that of the control group.
      Forty and 80 mg/l of fluoride induced significantly increased lactate
      dehydrogenase release, intracellular reactive oxygen species, and the percentage
      of apoptosis. Compared with control group, the malondialdehyde levels were
      significantly elevated while glutathione levels and glutathione peroxidase
      activities were decreased in all fluoride-treated groups, accompanied by the
      markedly reduced superoxide dismutase activity in 80 mg/l fluoride-treated group.
      With respect to NCAM mRNA expression levels, a significant dose-dependent
      decrease was observed in 40 and 80 mg/l fluoride-treated groups against the
      control group. In addition, as compared to the control group, the protein
      expression levels of NCAM-180 in 40 and 80 mg/l fluoride-treated groups, NCAM-140
      in all fluoride-treated groups, and NCAM-120 in the 80 mg/l fluoride-treated
      group were significantly decreased. Our study herein suggested that fluoride
      could cause oxidative stress, apoptosis, and decreased mRNA and protein
      expression levels of NCAM in rat hippocampal neurons, contributing to the
      neurotoxicity induced by fluoride.

PMID- 17537563
TI  - Innate host defense: Nox and Duox on phox's tail.
AB  - Over the past decade, the capacity of non-phagocytic cells to produce superoxide
      has been largely documented. As in the case of the well-characterized phagocytic
      cells context, superoxide formation in non-phagocytic cells depends on the
      activity of membrane bound NADPH oxidase enzymes. Six mammalian homologues of the
      classical phagocytic Nox2 enzyme have been described to date, named Nox1, Nox3,
      Nox4, Nox5, Duox1 and Duox2, which exhibit similar and specific structure and
      regulation features. Their biological functions are still poorly understood and
      were initially mostly deduced from their specific tissue expression profiles.
      However, recent functional data have emerged that suggest the involvement of
      several of these isoforms in the innate host response to invading microorganisms,
      including innate immune and proinflammatory responses. Nox2 is well characterized
      as a key player in the bacterial killing process that takes place in phagocytes.
      Here, we will discuss the recent advances that revealed alternative roles of
      Nox1, Nox4, Duox1 and Duox2 isoforms in other aspects of the innate host defense.
      In particular, we will focus on their implication in the signaling following
      pathogen recognition by toll like receptors and in the modulation of dendritic
      cell functions, two key aspects of innate immunity. Moreover, the potential role
      of Nox/Duox enzymes in the innate response to virus infections will be discussed.

PMID- 17537564
TI  - Semaphorins in development and adult brain: Implication for neurological
      diseases.
AB  - As a group, Semaphorins are expressed in most tissues and this distribution
      varies considerably with age. Semaphorins are dynamically expressed during
      embryonic development and their expression is often associated with growing
      axons. This expression decreases with maturity and several observations support
      the idea that in adult brain the expression of secreted Semaphorins is sensitive
      to electrical activity and experience. The functional role of Semaphorins in
      guiding axonal projections is well established and more recent evidence points to
      additional roles in the development, function and reorganization of synaptic
      complexes. Semaphorins exert the majority of their effects by binding to cognate
      receptor proteins through their extracellular domains. A common theme is that
      Semaphorin-triggered signalling induces the rearrangement of the actin and
      microtubule cytoskeleton. Mutations in Semaphorin genes are linked to several
      human diseases associated with neurological changes, but their actual influence
      in the pathogenesis of these diseases remains to be demonstrated. In addition,
      Semaphorins and their receptors are likely to mediate cross-talk between neurons
      and other cell types, including in pathological situations where their influence
      can be damaging or favourable depending on the context. We discuss how the
      manipulation of Semaphorin function might be crucial for future clinical studies.

PMID- 17537565
TI  - Association of Mayer-Rokitansky-Kuster-Hauser syndrome with Thrombocytopenia
      Absent Radii syndrome: a rare presentation.

PMID- 17537566
TI  - Evaluation of the sensitivity, specificity, positive and negative predictive
      values of preoperative magnetic resonance imaging for staging endometrial cancer.
      A prospective study of 100 cases at the Dorset Cancer Centre.
AB  - OBJECTIVES: The objectives were to evaluate the sensitivity and specificity of
      preoperative magnetic resonance imaging (MRI) in predicting myometrial invasion
      and disease stage in cases of endometrial carcinoma. STUDY DESIGN: Prospective
      analytic study in 100 sequential cases of endometrial carcinoma referred to the
      Dorset Cancer Centre between January 1999 and July 2004. The study included 100
      women with histologically proven endometrial malignancy, the mean age of the
      studied population being 68.6 years +/-2S.D. The preoperative MRI findings were
      compared with final surgical and histological staging; the latter was taken as
      the gold standard. The main outcome measures were the sensitivity and specificity
      of preoperative MRI for staging endometrial cancer. RESULTS: A total of 100
      consecutive cases of endometrial cancer were analysed, of which 62 cases were
      classified as stage Ia/Ib (early disease) by histology. MRI accurately predicted
      the degree of invasion in 54 cases and overestimated in 8, giving a sensitivity
      of 87% and specificity of 90%. In stage Ic disease the sensitivity and
      specificity of MRI were 56 and 86%, respectively. However, MRI showed
      significantly reduced sensitivity for predicting stage II endometrial cancer at
      19% but was found to be both sensitive and specific for predicting advanced
      endometrial cancer (stages III and IV); the sensitivity and specificity were 100
      and 99%, respectively. CONCLUSIONS: The accuracy of MRI scanning in predicting
      early and advanced endometrial disease is very good, but there is reduced
      accuracy with stage Ic and stage II disease. MRI is a valuable imaging modality
      in the preoperative assessment of cases of endometrial cancer.

PMID- 17537567
TI  - Contraceptive practices and trends in Spain: 1997-2003.
AB  - OBJECTIVE: To know the contraceptive use and trends in the Spanish female
      population. STUDY DESIGN: Since 1997, we have conducted a survey every 2 years on
      the use of contraceptive methods among a representative sample of Spanish women
      of childbearing potential (15-49 years). RESULTS: In the period 1997-2003, the
      percentage of use of contraceptive methods in Spain rose from 55.6% to 71.2%. The
      most commonly used method was the condom (21% in 1997, 21.9% in 1999, 29.5% in
      2001 and 35.7% in 2003), followed by the contraceptive pill (14.2%, 16.5%, 19.2%
      and 18.3%, respectively). Male or female sterilization remained stable with
      percentages of use of 5-7%. IUDs are used by about 5% of women. CONCLUSIONS: The
      use of contraceptive methods among Spanish women of childbearing potential
      generally fits quite well the patterns found in other developed countries, and we
      observed a trend towards increased use of effective methods.

PMID- 17537568
TI  - Coupling and internal noise sustain synchronized oscillation in calcium system.
AB  - In this work, the effects of coupling on two calcium subsystems were
      investigated, the cooperation between coupling and internal noise was also
      considered. When two non-identical subsystems are in steady state, coupling can
      induce oscillations, and distinctly enlarge the oscillatory region in bifurcation
      diagram. Besides, coupling can make the two non-identical oscillators
      synchronized. With the increment of the coupling strength, the cross-correlation
      time of the two oscillators firstly increases and then decreases to be constant,
      showing the synchronization without tuning coupling strength. When internal noise
      is considered, similar phenomena can also be obtained under the cooperation
      between coupling and internal noise.

PMID- 17537569
TI  - Multiple sclerosis and gluten sensitivity.
AB  - OBJECTIVE: To compare the frequency of gluten sensitivity in patients with
      multiple sclerosis (MS) and healthy controls. PATIENTS AND METHODS: The patients
      were 161 clinically definite MS patients who referred to neurology outpatient
      clinic of Nemazee Hospital, Shiraz, south of Iran from March 2004 to October
      2005. IgG and IgA antigliadin antibodies were measured by enzyme immuno assay
      (EIA) method. The test of IgA antitranstissue glutaminase (tTG) and duodenal
      biopsy were carried out in patients with either IgA or IgG AGA positive sera.
      Antigliadin antibodies were also measured for 166 age and sex matched control
      group. RESULTS: Neither IgG nor IgA antigliadin antibodies showed significant
      differences between MS patients and controls. Anti-tTG antibody and
      histopathologic studies were negative in all patients with positive IgG or IgA
      antigliadin antibodies results. Mean values of IgG and IgA antigliadin antibodies
      in MS patients with different sex, age, course, and functional systems
      involvement were not significantly different. CONCLUSION: Gluten sensitivity is
      not associated with MS in Iran.

PMID- 17537570
TI  - Migrainous infarction with appearance of laminar necrosis on MRI.
AB  - Although there is accepted criteria for migrainous infarction, the
      pathophysiology of this disease process remains poorly defined. Delineation of
      MRI characteristics of migrainous infarction may improve our understanding of the
      pathophysiology, diagnosis, and prognosis of this disorder. We present a case of
      a migrainous infarction that involved apparent laminar necrosis of a "cortical
      ribbon" of the right temporal, parietal, and occipital lobes.

PMID- 17537571
TI  - Eps8 is increased in pancreatic cancer and required for dynamic actin-based cell
      protrusions and intercellular cytoskeletal organization.
AB  - We investigated the role of Eps8 in pancreatic cancer. Eps8 was significantly
      increased in pancreatic cancer and colocalized with F-actin, predominantly in
      pancreatic ductal cells. Eps8 levels were higher in cell lines derived from
      ascites and metastases than in those from primary tumors. Expression correlated
      positively with the migratory potential of tumor cells. Eps8 localized to the
      tips of F-actin filaments, filopodia, and the leading edge of cells. Eps8
      knockdown altered cell shape and actin-based cytoskeletal structures, impairing
      protrusion formation and cell-cell junctions. We concluded that Eps8 is increased
      in pancreatic cancer and correlates with migratory potential and tumor
      progression in vitro. Eps8 is essential for actin dynamics and cell interactions,
      independent of Eps8-like gene products.

PMID- 17537572
TI  - Wet electrolytic oxidation of organic sludge.
AB  - Electrolysis of an aqueous solution at subcritical water conditions, referred
      here as wet electrolytic oxidation (WEO), results in a completely different
      reaction product compared to that from usual water electrolysis. Oxygen, hydrogen
      and chlorine evolution is almost completely suppressed when carrying out the
      electrolysis of aqueous NaCl solution at temperatures higher than 250 degrees C.
      Chemical oxygen demand (COD) compounds can be completely mineralized by this
      electrolytic reaction, but this work focused in partial oxidation of organic
      sludge and combining with biological process. The treatment of organic sludge by
      WEO increased the biodegradability of organic sludge due to the formation of
      organic acids. The electrochemical reaction of WEO suppressed the evolution of
      color that often appears in subcritical water treatment of organic waste.

PMID- 17537573
TI  - Wet peroxide oxidation and catalytic wet oxidation of stripped sour water
      produced during oil shale refining.
AB  - Catalytic wet oxidation (CWO) and wet peroxide oxidation (WPO) of stripped sour
      water (SSW) from an oil shale refinery was investigated. Greater than 70% total
      organic carbon (TOC) removal from SSW was achieved using Cu(NO(3))(2) catalysed
      WO under the following conditions using a glass lined reaction vessel: 200
      degrees C, pO(2)=0.5MPa, 3h, [Cu(NO(3))(2)]=67mmol/L. Significant TOC removal (
      approximately 31%) also occurred in the system without added oxygen. It is
      proposed that this is predominantly due to copper catalysed oxidative
      decarboxylation of organics in SSW based on observed changes in copper oxidation
      state. Greater than 80% TOC removal was achieved using WPO under the following
      conditions: 150 degrees C, t=1.5h, [H(2)O(2)]=64g/L. Significantly more TOC could
      be removed from SSW by adding H(2)O(2) in small doses as opposed to adding the
      same total amount in one single dose. It was concluded that WPO was a far more
      effective process for removing odorous compounds from SSW.

PMID- 17537574
TI  - Behavior of aluminum electrodes in electrocoagulation process.
AB  - In the present work, electrocoagulation process with aluminum electrodes was
      investigated. Different operational conditions such as composition of Na(2)SO(4)
      based solutions, pH and current density were examined in a systematic manner.
      Their influence on (i) electrode polarization phenomena, (ii) pH evolution during
      electrolysis and (iii) the amount of Al released (coagulant) was investigated.
      For this purpose, potentiodynamic tests and electrolyses using different
      electrochemical cell configurations were conducted. It is mainly found that (i) a
      minimum Cl(-) concentration of the electrolyte of about 60ppm is required to
      breakdown the anodic passive film and considerably reduce the cell voltage during
      electrolysis; (ii) the anodic dissolution efficiency is unit; (iii) the global
      amount of coagulant (Al(3+)) generated has two origins: electrochemical oxidation
      of the anode and "chemical" attack of the cathode and (iv) electrolysis with Al
      electrodes acts as pH neutralization of the electrolytic medium. Taking into
      account advantage of the pH evolution observed during electrolysis,
      electrocoagulation tests were performed to treat a synthetic wastewater
      containing heavy metallic ions (Ni(2+), Cu(2+), Zn(2+)). Removal efficiencies
      over 98% were reached. Furthermore, our results displayed prominently that an
      increase of current density notably reduces the treatment duration without
      inducing a strong increase of the charge loading.

PMID- 17537575
TI  - Extinction is not a natural consequence of unilateral spatial neglect: evidence
      from contrast detection experiments.
AB  - To investigate whether the expression of visual extinction is dependent upon the
      contralesional low saliency existing in neglect, we tested stroke patients with
      neglect and extinction, as well as normal controls, on detection of a peripheral
      Gabor patch, while a competing patch was presented simultaneously on the other
      side. To compensate for uneven saliency we set the contrast level relative to the
      detection threshold on each side. Patients showed contralesional extinction even
      for stimuli set at threshold level. They differed from controls in their
      sensitivity to changes in relative contrast between sides, showing stronger
      tendency for extinction and requiring much higher contrast increments in the
      target patch in order to eliminate extinction. The differences between normal and
      pathological extinction, shown despite compensation for contralesional perceptual
      attenuation due to neglect, suggest an additional extinction-specific deficit
      related to an abnormal interplay between the bilaterally presented stimuli. These
      findings have important theoretical implications concerning the relationship
      between neglect and extinction. They demonstrate that the hypothetical
      'attentional gradient', taken to explain reduced saliency of stimuli in the
      neglected side, cannot fully account for the phenomenon of extinction.

PMID- 17537576
TI  - Association study of two genetic variants in mitochondrial transcription factor A
      (TFAM) in Alzheimer's and Parkinson's disease.
AB  - Mitochondrial (mt) dysfunction has been implicated in Alzheimer's (AD) and
      Parkinson's disease (PD). Mitochondrial transcription factor A (TFAM) is needed
      for mtDNA maintenance, regulating mtDNA copy number and is absolutely required
      for transcriptional initiation at mtDNA promoters. Two genetic variants in TFAM
      have been reported to be associated with AD in a Caucasian case-control material
      collected from Germany, Switzerland and Italy. One of these variants was reported
      to show a tendency for association with AD in a pooled Scottish and Swedish case
      control material and the other variant was reported to be associated with AD in a
      recent meta-analysis. We investigated these two genetic variants, rs1937 and
      rs2306604, in an AD and a PD case-control material, both from Sweden and found
      significant genotypic as well as allelic association to marker rs2306604 in the
      AD case-control material (P=0.05 and P=0.03, respectively), where the A-allele
      appears to increase risk for developing AD. No association was observed for
      marker rs1937. We did not find any association in the PD case-control material
      for either of the two markers. The distribution of the two-locus haplotype
      frequencies (based on rs1937 and rs2306604) did not differ significantly between
      affected individuals and controls in the two sample sets. However, the global P
      value for haplotypic association testing indicated borderline association in the
      AD sample set. Our data suggests that the rs2306604 A-allele could be a moderate
      risk factor for AD, which is supported by the recent meta-analysis.

PMID- 17537578
TI  - Absence of correlation between karyotype profiles of Trypanosoma congolense and
      resistance to isometamidium chloride.
AB  - Chromosome profiles of 10 Trypanosoma (T.) congolense populations with different
      isometamidium sensitivities were compared using the pulsed field gel
      electrophoresis technique. The aim was to elucidate whether there was a karyotype
      pattern specific to eight isometamidium resistant phenotypes. Analysis of the
      profiles indicated that all populations displayed several discrete bands at the
      region of small, intermediate and large chromosomes. The highest similarity was
      observed between two isolates originating from Burkina Faso, indicating that they
      had the same genetic origin. Other eight strains exhibited different patterns in
      terms of chromosome size and numbers such that there was no characteristic
      karyotype pattern that was established specifically to identify resistant
      populations and discriminate them from the sensitive ones. This study has
      revealed that isometamidium resistance is not correlated to karyotype profile in
      T. congolense.

PMID- 17537577
TI  - Electroacupuncture-induced analgesia in a rat model of ankle sprain pain is
      mediated by spinal alpha-adrenoceptors.
AB  - In a previous study, we showed that electroacupuncture (EA) applied to the SI-6
      point on the contralateral forelimb produces long-lasting and powerful analgesia
      in pain caused by ankle sprain in a rat model. To investigate the underlying
      mechanism of EA analgesia, the present study tested the effects of various
      antagonists on known endogenous analgesic systems in this model. Ankle sprain was
      induced in anesthetized rats by overextending their right ankle with repeated
      forceful plantar flexion and inversion of the foot. When rats developed pain
      behaviors (a reduction in weight-bearing of the affected hind limb), EA was
      applied to the SI-6 point on the contralateral forelimb for 30 min under
      halothane anesthesia. EA significantly improved the weight-bearing capacity of
      the affected hind limb for 2h, suggesting an analgesic effect. The alpha
      adrenoceptor antagonist phentolamine (2mg/kg, i.p. or 30 microg, i.t.) completely
      blocked the EA-induced analgesia, whereas naloxone (1mg/kg, i.p.) failed to block
      the effect. These results suggest that EA-induced analgesia is mediated by alpha
      adrenoceptor mechanisms. Further experiments showed that intrathecal
      administration of yohimbine, an alpha(2)-adrenergic antagonist, reduced the EA
      induced analgesia in a dose-dependent manner, whereas terazosin, an alpha(1)
      adrenergic antagonist, did not produce any effect. These data suggest that the
      analgesic effect of EA in ankle sprain pain is, at least in part, mediated by
      spinal alpha(2)-adrenoceptor mechanisms.

PMID- 17537579
TI  - Molecular modeling and functional analysis of the AtoS-AtoC two-component signal
      transduction system of Escherichia coli.
AB  - The AtoS-AtoC two-component signal transduction system positively regulates the
      expression of the atoDAEB operon in Escherichia coli. Upon acetoacetate
      induction, AtoS sensor kinase autophosphorylates and subsequently phosphorylates,
      thereby activating, the response regulator AtoC. In a previous work we have shown
      that AtoC is phosphorylated at both aspartate 55 and histidine73. In this study,
      based on known three-dimensional structures of other two component regulatory
      systems, we modeled the 3D-structure of the receiver domain of AtoC in complex
      with the putative dimerization/autophosphorylation domain of the AtoS sensor
      kinase. The produced structural model indicated that aspartate 55, but not
      histidine 73, of AtoC is in close proximity to the conserved, putative phosphate
      donor, histidine (H398) of AtoS suggesting that aspartate 55 may be directly
      involved in the AtoS-AtoC phosphate transfer. Subsequent biochemical studies with
      purified recombinant proteins showed that AtoC mutants with alterations of
      aspartate 55, but not histidine 73, were unable to participate in the AtoS-AtoC
      phosphate transfer in support of the modeling prediction. In addition, these AtoC
      mutants displayed reduced DNA-dependent ATPase activity, although their ability
      to bind their target DNA sequences in a sequence-specific manner was found to be
      unaltered.

PMID- 17537580
TI  - Long-term immunosuppression in burned patients assessed by in vitro neutrophil
      oxidative burst (Phagoburst).
AB  - OBJECTIVE: To assess the duration and magnitude of immunosuppression induced by
      burns as measured by the neutrophil oxidative burst in vitro. DESIGN: Prospective
      exploratory cohort study. SETTING: Tertiary referral unit, University Hospital,
      Linkoping, Sweden (National Burn Unit). PATIENTS AND HEALTHY VOLUNTEERS
      (CONTROLS): Twenty-eight subjects consecutively admitted to the Burn Unit. The
      mean total burn surface area (TBSA%) was 36 (range 13-87) and mean age 44 years
      (range 14-89). Patients' data were collected prospectively in the burn unit,
      which also included sequential organ failure assessment (SOFA) score.
      INTERVENTIONS: None. MEASUREMENTS AND RESULTS: To assess the changes in the
      oxidative capacity of neutrophils after the burn, blood samples for the
      Phagoburst analysis were taken on admission and at least once every second week
      for the duration of stay in hospital and thereafter monthly up to 12 months after
      the burn. Neutrophils were stimulated in vitro by Escherichia coli, phorbol 12
      phorbol myristate 13-acetate (PMA), and peptide N-formyl-Met-Leu-Phe (fMLP).
      Oxidative burst was measured by flow cytometry. Oxidative capacity of the
      neutrophils decreased similarly for all three stimulants: there was a
      pathological decrease shortly after admission, with the lowest value occurring
      between days 7 and 10, followed by a gradual recovery during the ensuing months.
      Full recovery (to the values of the controls) was seen first 3.5 months after the
      burn. Using multiple regression, we found that only age and time since the burn
      significantly (p<0.05) affected the oxidative burst. White cell count (WCC) and C
      reactive protein (CRP) values returned to reference ranges long before the
      oxidative burst. CONCLUSIONS: This study provides evidence that immunosuppression
      in those injured by burns, as assessed by the in vitro oxidative burst of
      neutrophils, remains long after the event of the burn (up to 3.5 months after
      burn). Absence of correlations to TBSA%, FTB%, blood transfusion, opiates
      provided, and multiple organ failure score and laboratory infection variables
      together with the finding that decreased oxidative burst was uniform after the
      injury, suggesting that this immunosuppression is primarily due to the general
      metabolic response rather than recurring infections.

PMID- 17537581
TI  - A skin substitute (Integra) in a successful delayed reconstruction of a severe
      injured hand.

PMID- 17537582
TI  - Alcohol in emerging adulthood: 7-year study of problem and dependent drinkers.
AB  - OBJECTIVE: This study examined the level, changes and predictors of alcohol
      consumption and binge drinking over a 7-year period among young adults (18-25
      years) who met the criteria for problem drinking. METHOD: Interviews with 270 18
      to 25 years old problem and dependent drinkers from representative public and
      private substance use treatment programs and the general population were
      conducted after 1, 3, 5, and 7 years. Measures included demographic
      characteristics, severity measures, and both formal and informal influences on
      drinking. RESULTS: Overall alcohol consumption declined over time but leveled off
      around 24 years of age. Being male, not attending AA over time, as well as more
      baseline dependence symptoms and greater ASI alcohol and legal severity were
      associated with greater consumption and binge drinking. In addition, greater
      levels of binge drinking were associated with less education, earlier age of
      first use, and a larger social network of heavy drinkers. In conclusion, more
      attention should be paid to heavy drinking among young adults and to the factors
      that influence their drinking patterns.

PMID- 17537583
TI  - Reactivity to nicotine cues over repeated cue reactivity sessions.
AB  - The present study investigated whether reactivity to nicotine-related cues would
      attenuate across four experimental sessions held 1 week apart. Participants were
      nineteen non-treatment seeking, nicotine-dependent males. Cue reactivity sessions
      were performed in an outpatient research center using in vivo cues consisting of
      standardized smoking-related paraphernalia (e.g., cigarettes) and neutral
      comparison paraphernalia (e.g., pencils). Craving ratings were collected before
      and after both cue presentations while physiological measures (heart rate, skin
      conductance) were collected before and during the cue presentations. Although
      craving levels decreased across sessions, smoking-related cues consistently
      evoked significantly greater increases in craving relative to neutral cues over
      all four experimental sessions. Skin conductance was higher in response to
      smoking cues, though this effect was not as robust as that observed for craving.
      Results suggest that, under the described experimental parameters, craving can be
      reliably elicited over repeated cue reactivity sessions.

PMID- 17537584
TI  - Cannabis use and suicidal behaviours in high-school students.
AB  - The aim of the study was to evaluate the relative contributions of cannabis use,
      depressive and anxious symptoms in the prediction of suicidal behaviors.
      Participants were 248 high-school students who completed questionnaires assessing
      cannabis use, suicidal behaviors, depressive and anxious symptoms. Cannabis use
      was a significant independent predictor of suicidal behaviors after adjustment
      for depressive and anxious symptoms.

PMID- 17537585
TI  - Single-session expectancy challenge with young heavy drinkers on holiday.
AB  - Expectancy challenges (ECs) were used to change alcohol expectancies and alcohol
      consumption in young heavy drinking men (age 16-24) on holiday. The intervention
      took place in community centers and bars. Alcohol expectancies and consumption
      were assessed with paper and pencil measures prior to the intervention (N=301)
      and 2 days afterwards (EC: n=178; controls: n=86). Six weeks after the EC,
      participants were interviewed by telephone (EC: n=163; controls: n=71). The
      intervention resulted in an increase in sedation expectancies in the EC group.
      Furthermore, the EC led to a differential reduction in alcohol consumption on a
      night out at the six-week posttest in the heaviest drinkers only. The reduction
      in alcohol consumption on a night out was not mediated by the change in sedation
      expectancies. These findings suggest that further research on the mechanisms of
      change is necessary before a single-session EC may be used in a real-life
      prevention setting.

PMID- 17537586
TI  - Personalizing the alcohol-IAT with individualized stimuli: relationship with
      drinking behavior and drinking-related problems.
AB  - Research aimed at uncovering implicit cognitive processes involved in alcohol use
      and abuse has demonstrated that implicit attitudes toward alcohol are negative
      and unrelated to drinking behavior. Here, it was examined whether these findings
      could be due to contamination of the IAT by extrapersonal associations that are
      irrelevant to behavior. Participants performed a traditional alcohol-IAT as well
      as a personalized IAT, which has been demonstrated to reduce extrapersonal
      contamination. Additionally, the personalized IAT presented individualized
      stimuli, which should further reduce extrapersonal contamination. Consistent with
      this hypothesis, significantly weaker IAT effects emerged in the personalized IAT
      compared to the traditional IAT. However, both the traditional and personalized
      IAT still indicated negative implicit attitudes toward alcohol. Incremental
      predictive validity was demonstrated for both tasks. Importantly, these findings
      underscore the importance of implicit attitudes toward alcohol as determinants of
      alcohol use and abuse.

PMID- 17537587
TI  - Extraosseous osteosarcoma arising from the small intestinal mesentery.
AB  - Extraskeletal osteosarcoma (EOS) is a highly aggressive and exceedingly rare
      mesenchymal tumor. Due to the rare nature of the disease, the diagnosis can be
      difficult and is often confirmed only after diagnostic laparotomy and
      histopathology. We describe the clinical history, radiologic and histomorphologic
      presentation, and clinical management of a 61-year-old patient who presented with
      abdominal pain. Abdominal ultrasound and computerized tomography (CT) scan
      revealed a calcified intra-abdominal mass. Following an explorative laparotomy,
      histology showed a large extraosseous osteosarcoma of the small bowel mesentery.
      Therapy according to the Cooperative Sarcoma Study-96 (COSS-96) was commenced.
      Diagnosis, management, and outcome in the context of the current literature are
      discussed. To our knowledge, this is the first description of an extraosseous
      osteosarcomas in the small bowel mesentery in the literature.

PMID- 17537588
TI  - [Perinatal risk at term and post-term revisited].
AB  - The aim of this review was to revisit the evaluation of risk of foetal and
      neonatal mortality at term. We analyse the meaning of term period and difficulty
      to determine the normal duration of the pregnancy. Specific complications
      associated with post term and the statistic approach of the perinatal risk are
      analysed, together with various mortality rates and especially the prospective
      risk introducing foetal term as a new concept. We study various aspect and
      evolution of non specific morbidity of the term period. An optimal decision for
      term management should involve pregnant women and the analysed parameters should
      be taken into consideration.

PMID- 17537589
TI  - [The ovarian immature teratoma with gliomatosis peritonei].
AB  - OBJECTIVE: We return a case of ovarian immature teratoma with peritoneal
      gliomatose at a woman aged of 20 years. MATERIAL AND METHODS: The diagnosis
      discovered following pelvic mass increasing volume and treaty by a one-sided
      annexectomy, with chemotherapy. RESULTS: Eighty-seven cases have been published
      in the literature. Although potential for recurrence is high, the risk of
      malignancy is very low. CONCLUSION: Ovarian immature teratoma is a malignant germ
      cell tumor and represents less than 1% of ovarian malignant tumors. Tissues are
      derived from the three germ layers (endo-, meso- and ectoderm). Tumor grading is
      based on the amount of immature neuroepithelium present. The prognosis is
      directly correlated to histological grade. Rapid (fast) growth leads to large
      tumors with an early diagnosis. Gliomatosis peritonei is a rare situation,
      characterized by the recurrence of peritoneal implants after the surgical
      treatment of ovarian teratoma. This entity does not modify the good prognosis of
      mature teratomas, but we recommend regular follow-up.

PMID- 17537590
TI  - [Hypokaliemic periodic paralysis and pregnancy: perinatal management. A case
      report].
AB  - Familial hypokalemic periodic paralysis (FHPP) is a rare inherited disease
      characterized by a dysfunction of the membrane ion channels. Clinical
      manifestations are attacks of hypokaliemia with flaccid muscle paralysis.
      Paralysis is sometimes severe but always reversible with symptomatic treatment.
      Pregnancy and delivery have been reported to exacerbate FHPP. Authors report a
      case of FHPP during pregnancy with a favourable outcome. Vaginal delivery is
      usually possible with monitoring and epidural analgesia, avoiding active maternal
      expulsive efforts (passive descent of the fetus and elective outlet forceps) and
      other stimulating factors (carbohydrate loads, maternal stress, betamimetics,
      epinephrine...). Administration of IV potassium supplementation is often
      necessary.

PMID- 17537591
TI  - [Which is the role of parasites and yeasts in the genesis of chronic
      blepharitis?].
AB  - INTRODUCTION: The chronic blepharitis is a current ophthalmic disease posing a
      therapeutic problem. The etiologic diagnosis is essential for adapting the
      treatment. PURPOSE: The aim of this study is to describe the role of Demodex sp,
      Malassezia sp and Candida sp in the pathogenesis of chronic blepharitis. PATIENTS
      AND METHODS: It's a prospective study realized during a period of 14 months. It
      interested 69 patients with chronic blepharitis and 96 controls. The prevalence
      of Demodex sp, Malassezia sp and Candida sp on the eyelash of chronic blepharitis
      patients and controls was investigated. RESULTS: Demodex folliculorum was found
      in 58% of patients with chronic blepharitis and in 15,6% of controls. The
      difference between the two groups was statistically significant (P<0,00001). The
      sex and the age intervene neither in the frequency, nor in the abundance of D.
      folliculorum in the two groups. Malassezia sp was identified in 10,4% of the
      control group and 31,88% of the group with chronic blepharitis. The difference is
      significant (P<0,00001). There is no correlation between frequency and abundance
      of Malassezia, sex and age in the two groups. CONCLUSION: In our study, D.
      folliculorum and Malassezia sp seem to be accused in the genesis of the chronic
      blepharitis. Their systematic search is necessary in order to adapt the
      treatment.

PMID- 17537592
TI  - Coevolution between cannabinoid receptors and endocannabinoid ligands.
AB  - Genes for receptors and ligands must coevolve to maintain coordinated gene
      expression and binding affinities. Researchers have debated whether anandamide or
      2-arachidonyl glycerol (2-AG) is a more "intrinsic" ligand of cannabinoid
      receptors. We addressed this debate with a coevolutionary analysis, by examining
      genes for CB1, CB2, and ten genes that encode ligand metabolic enzymes:
      abhydrolase domain containing 4 protein, cyclooxygenase 2, diacylglycerol lipase
      paralogs (DAGLalpha, DAGLbeta), fatty acid amide hydrolase paralogs (FAAH1,
      FAAH2), monoglyceride lipase, N-acylethanolamine acid amidase, NAPE-selective
      phospholipase D, and protein tyrosine phosphatase non-receptor type 22. Gene
      trees (cladograms) of CB1, CB2, and ligand enzymes were obtained by searching for
      orthologs (tBLASTn) in the genomes of nine phylogenetically diverse species,
      aligning ortholog sequences with ClustalX, and applying Bayesian analysis
      (MrBayes). Mirrored cladograms provided evidence of coevolution (i.e., parallel
      cladogenesis). Next we constructed phylograms of CB1, CB2, and the ten enzymes.
      Phylogram branch lengths were proportional to three sets of maximum likelihood
      metrics: all-nucleotide-substitutions and NS/SS ratios (using PAUP()), and Ka/Ks
      ratios (using FUGE). Spurious correlations in all-nucleotide-substitutions trees
      (due to phylogenetic bias) and in Ka/Ks ratio trees (due to simplistic modeling)
      were parsed. Branch lengths from equivalent branches in paired trees were
      correlated by linear regression. Regression analyses, mirrored cladograms, and
      phylogenetic profiles produced the same results: close associations between
      cannabinoid receptors and DAGL enzymes. Therefore we propose that cannabinoid
      receptors initially coevolved with a fatty acid ester ligand (akin to 2-AG) in
      ancestral metazoans, and affinity for fatty acid ethanolamide ligands (e.g., AEA)
      evolved thereafter.

PMID- 17537593
TI  - Evidence for recombination between feminizing Wolbachia in the isopod genus
      Armadillidium.
AB  - Wolbachia are maternally inherited endosymbiotic alpha-Proteobacteria infecting a
      wide range of arthropods. Wolbachia induce feminization in many terrestrial
      isopod species, particularly in the genus Armadillidium (Crustacea, Oniscidea).
      The diversity of Wolbachia strains infecting Armadillidium species was examined.
      Results reveal that natural populations of A. vulgare contain three different
      Wolbachia strains (wVulC, wVulM and wVulP). The wsp gene and its 3'-adjacent
      region show evidence that two recombination events have occurred between two of
      these strains. In both cases, multiple statistical analyses suggest that a small
      gene fragment of a strain closely related to wVulM (minor parent) is inserted
      into the genome of another strain closely related to wVulC (major parent).
      Although multiple infections in a single individual have never been demonstrated
      in natural population, the existence of recombination between feminizing strains
      suggests that bi-infections are possible, or at least that bi-infections can be
      maintained sufficiently long enough to allow recombination. Recombination events
      increase genetic diversity of Wolbachia found in Armadillidium species and may
      play a role in the ability of Wolbachia strains to invade new hosts.

PMID- 17537594
TI  - A neuroglobin-overexpressing transgenic mouse.
AB  - Neuroglobin (Ngb) is a recently discovered vertebrate globin expressed primarily
      in neurons. Ngb expression is induced by hypoxia and ischemia, and Ngb protects
      neurons from these insults. However, its normal physiological role and the
      mechanism underlying its neuroprotective action are uncertain. We report
      production of a transgenic mouse in which Ngb is overexpressed under the control
      of the chicken beta-actin promoter. This mouse should prove helpful for studying
      Ngb-mediated effects in vitro and in vivo.

PMID- 17537595
TI  - The effects of NBS1 knockdown by small interfering RNA on the ionizing radiation
      induced apoptosis in human lymphoblastoid cells with different p53 status.
AB  - Mutations of NBS1 are responsible for the human hereditary disease Nijmegen
      breakage syndrome (NBS), which is characterized by an extremely high cancer rate.
      In this study, we investigated the influence of NBS1 on ionizing radiation (IR)
      induced apoptosis. Using small interfering RNA (siRNA) transfection, we knocked
      down NBS1 protein in three closely related human lymphoblastoid cell lines
      differing in p53 status: TK6 with a wild-type p53, NH32 with a null mutation of
      p53, and WTK1 with a mutant p53. We found that up to 48h after 5Gy IR, all three
      lines showed an obvious induction of apoptosis regardless of the p53 status. The
      magnitude of apoptosis induction was TK6>NH32>WTK1. This suggested that although
      p53 is an important modulator of IR-induced apoptosis, other p53-independent
      apoptosis pathway also exists. Moreover, NBS1 knockdown led to reduction of IR
      induced apoptosis in all three lines and both NBS1/ATM/p53/BAX and
      NBS1/ATM/CHK2/E2F1 apoptosis pathways were partially inactivated. Our results
      suggest that NBS1 plays an important role in IR-induced apoptosis via both p53
      dependent and p53-independent mechanisms. The impaired apoptosis response to DNA
      damage in NBS1 deficient cells might be one of the important mechanisms of cancer
      predisposition in NBS patients.

PMID- 17537596
TI  - Expression stability of two housekeeping genes (18S rRNA and G3PDH) during in
      vitro maturation of follicular oocytes in buffalo (Bubalus bubalis).
AB  - The present study was undertaken to evaluate the expression stability of two
      housekeeping genes (HKGs), 18S rRNA and G3PDH during in vitro maturation (IVM) of
      oocytes in buffalo, which qualifies their use as internal controls for valid qRT
      PCR estimation of other oocyte transcripts. A semi quantitative RT-PCR system was
      used with optimised qRT-PCR parameters at exponential PCR cycle for evaluation of
      temporal expression pattern of these genes over 24 h of IVM. 18S rRNA was found
      more stable in its expression pattern than G3PDH.

PMID- 17537597
TI  - Exercise self-efficacy of postmenopausal women resident in the tropics.
AB  - OBJECTIVES: Weight gain and the associated increased risk of coronary artery
      disease are associated with the postmenopausal period. However, moderate
      intensity physical activity may be cardioprotective in this period. Australian
      women remain predominately sedentary despite the health benefits of regular
      exercise. Self-efficacy is an important predictor of exercise behaviour
      influencing exercise adoption when faced with potential barriers. Determination
      of exercise self-efficacy levels and the most significant barriers to exercise is
      necessary for the success of intervention programs for this population. METHODS:
      Postmenopausal women (N=101) resident in tropical North Queensland were recruited
      via announcements in local media, service club newsletters and electronic
      bulletin boards. Following data collection, participants were categorised as
      exercisers (n=53) or non-exercisers (n=48) based on whether they had performed a
      minimum of 150 min of accumulated moderate intensity exercise in the past 7 days.
      Exercise self-efficacy was determined via questionnaire. RESULTS: Results
      indicated that exercisers had a higher level of exercise self-efficacy and felt
      significantly more confident to exercise when faced with barriers compared to non
      exercisers (p<.001). Discriminant function analysis found that exercise self
      efficacy provided the greatest discrimination between exercisers and non
      exercisers. The barrier items of conflicting schedules, difficulty getting to an
      exercise location and the weather were the main contributors to discrimination
      between exercisers and non-exercisers. CONCLUSIONS: Findings suggest that future
      intervention programs should aim to increase exercise self-efficacy and address
      these barriers so that more postmenopausal women resident in North Queensland can
      obtain the health benefits of exercise.

PMID- 17537598
TI  - Carboxymethyl high amylose starch for F4 fimbriae gastro-resistant oral
      formulation.
AB  - The carboxymethyl high amylose starch (CM-HAS) was proposed as excipient able to
      protect F4 fimbriae oral vaccine against gastric acidity and pepsin, allowing its
      subsequent liberation in the intestinal fluid. Thus, F4 fimbriae formulated with
      CM-HAS as tablets displayed a markedly higher stability after 2h of incubation in
      simulated gastric fluid (containing pepsin) than the free, non-protected F4
      fimbriae, which, in these conditions, were almost completely digested after 120
      min. In the presence of pancreatin (with alpha-amylase, lipase and proteolytic
      activities) in simulated intestinal conditions, the F4 fimbriae were liberated
      from CM-HAS tablets over a period of up to 5 h. The presence of pancreatin in
      intestinal medium did not affect the structural stability of the F4 fimbriae
      major subunits. Thus, F4 fimbriae formulated with CM-HAS would retain their
      receptor binding activity essential for the induction of an intestinal mucosal
      immune response.

PMID- 17537599
TI  - Irradiation of human insulin in aqueous solution, first step towards
      radiosterilization.
AB  - The degradation of irradiated human insulin in aqueous solutions was investigated
      in order to protect the protein against ionizing radiation. The influence of the
      drug concentration, excipients and irradiation temperature were studied. Aqueous
      solutions at pH 2 were irradiated by gamma rays or by accelerated electrons. Two
      different high-performance liquid chromatography (HPLC) methods were used:
      reverse-phase high-performance liquid chromatography (RP-HPLC)/UV and size
      exclusion liquid chromatography (SEC/UV) to investigate both the fragmentation
      and the formation of higher molecular weight proteins. In solution without
      excipients irradiated at ambient temperature at 10 kGy, the loss of human insulin
      is almost complete. Addition of radio-protecting excipients (free radicals
      scavengers) and cryo-irradiation allowed to decrease insulin degradation. The
      best radio-protector used was ascorbic acid in aqueous solution and oxidized
      glutathione in the frozen solutions. Only the combination of these two approaches
      (addition of scavenger and freezing) enables the irradiated human insulin in
      aqueous solution to meet the European Pharmacopoeia requirements for chemical
      potency (>or=90%).

PMID- 17537600
TI  - A material science perspective of pharmaceutical solids.
AB  - This review introduces the basic material science concepts and principles behind
      some common topics in the development of pharmaceutical solid formulations. The
      physiochemical properties of small organic pharmaceutical materials are
      summarized. Common phases, differences in phases, phase transitions, and their
      relation to pharmaceutical development are reviewed. The characteristics and
      physical nature of solid phases, including crystalline and amorphous solids, are
      presented in conjunction with some pharmaceutically relevant phenomena, such as
      polymorphism, phase transition kinetics, and relaxation. Mesophases, including
      liquid crystals and condis crystals, are introduced. The potential energy states
      of different phases are highlighted as the key connection between the physical
      nature of the materials and their pharmaceutical behavior, and energy landscape
      is employed to enhance the understanding of this relation.

PMID- 17537601
TI  - Gels and liposomes in optimized ocular drug delivery: studies on ciprofloxacin
      formulations.
AB  - Ciprofloxacin (CPFX) containing therapeutic systems were developed using gel- and
      liposome-based formulations to minimize tear-driven dilution in the conjunctival
      sac, a long-pursued objective in ophthalmology. Physicochemical properties (pH,
      osmolarity, viscosity, expansivity, membrane fluidity and in vitro CPFX release
      rate) of the preparations were studied by the appropriate methods. For gel
      preparation, the bio-adhesive poly(vinyl alcohol) and polymethacrylic acid
      derivatives were applied in various concentrations. In our liposome-supported
      carrier systems, multilamellar vesicles from lecithin and alpha-L-dipalmithoyl
      phosphatidylcholine provided the encapsulating agent. Electron paramagnetic
      resonance (EPR) spectroscopy was applied to study the molecular interactions in
      the ophthalmic formulations. The polymer hydrogels used in our preparations
      ensured a steady and prolonged active ingredient release. In addition,
      encapsulation of the CPFX into liposomes prolonged the in vitro release of the
      antibacterial agent depending on the lipid composition of the vesicles.

PMID- 17537602
TI  - Direct and indirect antimicrobial effects and antioxidant activity of Cordia
      gilletii De Wild (Boraginaceae).
AB  - Cordia gilletii De Wild (Boraginaceae) root bark is traditionally used in
      Democratic Republic of Congo (DRC) for the treatment of various disorders,
      including malaria, diarrhea, wounds and skin diseases; part of these activities
      may rely on antimicrobial and antioxidant properties. Successive extracts of root
      barks powder with n-hexane, dichloromethane, ethyl acetate, methanol and water
      were tested for antimicrobial activity, both direct and indirect (antibiotic
      resistance reversal), against 10 strains of bacteria and 1 strain of fungi by
      broth microdilution and agar diffusion methods. The eventual synergy between
      plant extracts and antibiotics was investigated by the determination of the
      fractional inhibitory concentration index (FIC index). The methanol extract
      showed direct antimicrobial activity against all tested microorganisms with
      minimum inhibitory concentrations (MIC) ranging between 125 and 1000 microg/ml,
      whereas the ethyl acetate and the dichloromethane extracts showed activity on
      four and three strains, respectively. 200 microg/ml of n-hexane and
      dichloromethane extracts decreased the MICs of penicillin and streptomycin 4-64
      fold for methicillin-resistant Staphylococcus aureus. A synergistic effect was
      found between the methanol extract and tetracycline, whereas additive effects
      were observed for the other combinations tested. The methanol and dichloromethane
      extracts showed the greater antioxidant activity by scavenging the free radical
      DPPH with IC(50) values of 3.2 and 8.1 microg/ml, respectively. These results
      support the use of the plant in the treatment of infectious diseases and wounds;
      they warrant further studies as to the nature of active compounds.

PMID- 17537603
TI  - San-Huang-Xie-Xin-Tang inhibits Helicobacter pylori-induced inflammation in human
      gastric epithelial AGS cells.
AB  - Helicobacter pylori infection leads to gastroduodenal inflammation, peptic
      ulceration, gastric lymphoma and gastric cancer. Certain herbal remedies have
      been used to treat gastric disease. In this study, we examined the anti
      inflammatory effect of San-Huang-Xie-Xin-Tang (SHXT) and its main component
      baicalin on Helicobacter pylori-infected human gastric epithelial AGS cell. AGS
      cells were treated with Helicobacter pylori at a bacterium/cell ratio of 300:1.
      mRNA expression and protein levels were determined by reverse transcriptase
      polymerase chain reaction (RT-PCR) analysis and western blot analysis,
      respectively. Interleukin-8 (IL-8) level and the translocation of nuclear factor
      kappa B (NF-kappaB) were measured by enzyme-linked immunosorbent assay (ELISA)
      and enzyme-linked DNA-protein interaction assay (ELDIA), respectively. Nitric
      oxide production was measured by Griess reagent. We found that SHXT and baicalin
      inhibited Helicobacter pylori-induced cyclooxygenase-2 (COX-2) enhancement and
      IkappaBalpha degradation in both mRNA and protein levels. SHXT and baicalin also
      inhibited Helicobacter pylori-induced inducible nitric oxide synthase (iNOS) and
      IL-8 mRNA expression, and decreased NO and IL-8 production. Furthermore, SHXT and
      baicalin inhibited nuclear translocation of p50 subunit of NF-kappaB in
      Helicobacter pylori-infected AGS cells. Based on the above findings, SHXT and
      baicalin might exert anti-inflammatory and gastroprotective effects in
      Helicobacter pylori-induced gastric inflammation.

PMID- 17537605
TI  - Differentiation between peritrigonal terminal zones and hypoxic-ischemic white
      matter injury on MRI.
AB  - The differentiation between terminal zones and pathological signal intensity
      changes on MRI of children and young adults is of diagnostic importance. We
      assessed the diagnostic value of several morphological features on MRI to
      differentiate between terminal zones and hypoxic-ischemic white matter injury. We
      selected all brain MRI examinations performed in subjects up to 20 years of age
      showing increased signal intensity on T2-weighted images in the peritrigonal
      areas. 75 individuals were assigned to a patient group (n=28) if there was
      evidence of hypoxia-ischemia during the perinatal period or a control group
      (n=47). Aspect, location, extent, shape, and borders of signal intensity changes
      in the peritrigonal areas were studied. Signal intensity of the peritrigonal
      areas was related to signal intensity of surrounding white matter. Presence of
      Virchow Robin spaces, hypoxic-ischemic abnormalities, and local atrophy were also
      recorded. Chi-squared tests assessed whether presence or absence of morphological
      characteristics differed between patients and controls. Logistic regression
      analysis studied which characteristics were best to discriminate between the two
      groups. Very high signal intensity of the peritrigonal areas on FLAIR (Odds Ratio
      25) and presence of local atrophy (Odds Ratio 14.3) were best predictors to
      discriminate between the two groups.

PMID- 17537606
TI  - Diffusion-weighted MR imaging of kidneys in renal artery stenosis.
AB  - OBJECTIVE: The purpose of our study was to evaluate perfusion and diffusion of
      kidneys in renal artery stenosis (RAS) and any correlation between stenosis and
      ADC values and whether this imaging modality may be a noninvasive complementary
      assessment technique to MR angiography before interventional procedures.
      MATERIALS AND METHODS: Twenty consecutive patients suspected of having renal
      artery stenosis were evaluated with renal MR angiography to exclude stenosis and
      were then included in the study. Transverse DW multisection echo-planar MR
      imaging was performed. In the transverse ADC map, rectangular regions of interest
      were placed in the cortex on 3 parts (upper, middle, and lower poles) in each
      kidney. ADCs of the kidneys were calculated separately for the low, average, and
      high b-values to enable differentiation of the relative influence of the
      perfusion fraction and true diffusion. The ADC values of 39 kidneys (13 with
      renal artery stenosis and 26 normal renal arteries) were compared, and the
      relationship between stenosis degree and ADC values was calculated. RESULTS: RAS
      was detected in 11 of 20 (55%) patients with MRA. Thirteen of 39 kidneys
      demonstrated RAS, and 26 were normal. The ADClow (1.9+/-0.2 versus 2.1+/-0.2;
      P=.020), ADCaverage (1.7+/-0.2 versus 1.9+/-0.1; P=.006), and ADChigh (1.8+/-0.2
      versus 2.0+/-0.1; P=.012) values were significantly lower in patients with
      kidneys with arterial stenosis than that in patients with kidneys with normal
      arteries. Statistical analysis revealed that stenosis degree correlated strongly
      with ADClow (r=-.819; P=.001), ADCaverage (r=-.754; P=.003), and ADChigh (r=
      .788; P=.001). The ADClow, ADCaverage, and ADChigh values were significantly
      lower in patients with kidneys with arterial stenosis than that in patients with
      kidneys with normal arteries. CONCLUSION: We think that DW MR imaging of kidneys
      with RAS can help determine the functional status of a renal artery stenosis.

PMID- 17537607
TI  - Acute eosinophilic pneumonia: Thin-section CT findings in 29 patients.
AB  - PURPOSE: To determine thin-section computed tomography (CT) characteristics of
      acute eosinophilic pneumonia (AEP). MATERIALS AND METHODS: Thin-section CT scans
      of 29 patients (14 males, 15 females; mean age, 26+/-15 years; age range, 15-72
      years) with AEP were included this retrospective study. The clinical diagnosis of
      AEP was established by Allen's criteria. Each thin-section CT was reviewed by two
      observers. RESULTS: Bilateral areas with ground-glass attenuation were observed
      on thin-section CT in all patients. Areas of air-space consolidation were present
      in 16 (55%) of 29 patients. Poorly defined centrilobular nodules were present in
      9 patients (31%). Interlobular septal thickening was present in 26 patients
      (90%). Thickening of bronchovascular bundles was present in 19 patients (66%).
      Pleural effusions were present in 23 patients (79%) (bilateral=22, right side=1,
      left side=0). The predominant overall anatomic distribution was central in only 2
      (7%) of 29 patients, peripheral in 9 patients (31%), and random in 18 patients
      (62%). The overall zonal predominance was upper in 4 patients (14%), lower in 8
      patients (28%), and random in 17 patients (58%). CONCLUSION: CT findings in AEP
      patients consisted mainly of bilateral areas of ground-glass attenuation,
      interlobular septal thickening, thickening of bronchovascular bundles, and the
      presence of a pleural effusion without cardiomegaly. The most common overall
      anatomic distribution and zonal predominance of the abnormal CT findings were
      random.

PMID- 17537609
TI  - Development of gas chromatographic/mass spectrometry-pattern recognition method
      for the quality control of Korean Angelica.
AB  - This paper describes gas chromatographic/mass spectrometry (GC/MS)-pattern
      recognition methods for the quality control of Korean Angelica. A total of 57
      Angelicae radix samples, including Angelica gigas (Korean origin), A. sinensis
      (Chinese origin) and A. acutiloba (Japanese origin), were analyzed by GC/MS, with
      a principal component analysis (PCA) subsequently applied to 10 common peaks
      selected from each chromatogram. As a result, the samples were clustered
      according to their origins on the PC score plot. The loading plot revealed that
      decursin and decursinol angelate were the most contributive principles
      distinguishing Korean samples from Chinese and Japanese samples, In addition, a
      discriminant model was developed for classification of the Angelicae radix, using
      a discriminant analysis (DA), and validated with a training set (three from A.
      gigas, four from A. sinensis, and three from A. acutiloba). All samples tested
      were successfully classified according to their species origin.

PMID- 17537608
TI  - A comparative study of capillary zone electrophoresis and pH-potentiometry for
      determination of dissociation constants.
AB  - Acidity constants of six cephalosporin antibiotics, cefalexin, cefaclor,
      cefadroxil, cefotaxim, cefoperazon and cefoxitin are determined using capillary
      zone electrophoresis (CZE) and pH-potentiometric titrations. Since CZE is a
      separation method, it is not necessary for the samples to be of high purity and
      known concentration because only mobilities are measured. The effect on
      determination of dissociation constants of different matrices (serum, 0.9% NaCl,
      fermentation matrix) was examined. The advantages of CZE can be utilized in those
      fields where potentiometry has limitations (sample quantity, solubility, purity,
      simultaneous determinations), although pK(a) values that are close to each other
      can be determined by potentiometry with more accuracy.

PMID- 17537610
TI  - Potential employment of non-silica-based stationary phases in pharmaceutical
      analysis.
AB  - The absolute majority of the HPLC applications use silica-based columns for the
      separation of active substance and its impurities. However, stationary phases
      based on metal oxides appear as an interesting alternative. The aim of our study
      was to investigate the potential utilization of metal oxide-based stationary
      phases in analytical evaluation of ondansetron and its five pharmacopoeial
      impurities. In our study commercially available ZrO(2)-based columns (e.g. Zr
      PBD, Zr-PS, Zr-C18) and TiO(2)-based column were used. The effect of an organic
      modifier (type and ratio), a buffer (type, pH and concentration) and the
      influence of temperature was investigated. The separation of ondansetron and its
      five pharmacopoeial impurities was successfully accomplished on a Zirchrom-PBD
      column using a mobile phase consisting of acetonitrile-ammonium phosphate (25 mM,
      pH 7.0) (18:82, v/v). Detection was performed at 216 nm and the analysis was
      completed within 7.5 min. The paper proves metal oxide-based stationary phases as
      an alternative to classical silica-based stationary phases in pharmaceutical
      analysis.

PMID- 17537611
TI  - A novel antibiotic bone assay by liquid chromatography/tandem mass spectrometry
      for quantitation of tigecycline in rat bone.
AB  - Tigecycline (Tygacil) is a first-in-class, broad spectrum antibiotic with
      activity against antibiotic-resistant organisms. In rats and humans, tigecycline
      readily distributes to bone tissue but its accuracy of quantitation via liquid
      chromatography/mass spectrometry (LC/MS/MS) is hindered by a low extraction
      recovery when using a conventional plasma extraction method. To overcome this
      issue, we have identified an effective extraction solvent for quantitation of
      tigecycline in rat bone. The current LC/MS/MS bone assay is novel, simple, and
      sensitive, and has a wide linear range of 50-10,000 ng/g. The assay requires
      homogenization of the rat bone in a strong acidic-methanol extraction solvent,
      centrifugation of the bone suspension, separation of the supernatant with liquid
      chromatography, and detection of tigecycline with tandem mass spectrometry. The
      incurred pooled rat bone samples obtained from rats given 3mg/kg/day of [(14)C]
      tigecycline and non-radio-labeled tigecycline were analyzed with the current
      method. The absolute extraction recovery of the bone assay for tigecycline was
      77.1%. The intra-day accuracy ranged from 91.7 to 106% with precision (CV) of 1.9
      10.7%, and inter-day accuracy ranged from 96.1 to 100% with a precision of 6.3
      8.7%. In addition, biological activity was demonstrated for the tigecycline
      extracted from incurred rat bone. This bone assay provides an important
      analytical tool for the determination of drug concentrations (especially,
      antimicrobials) in rodent bone tissues and has served as the foundation of
      development and validation of a similar bone assay for tigecycline in human bone
      tissues.

PMID- 17537612
TI  - Provider and patient perspectives regarding health care for war-related health
      concerns.
AB  - OBJECTIVE: To gain insight about Department of Defense providers' and health care
      beneficiaries' opinions regarding provider-patient communication of health care
      for post-deployment health concerns. METHODS: Thirty-five Department of Defense
      primary care providers and 14 military beneficiaries participated in focus groups
      at five military medical treatment facilities. We audiotaped, transcribed, and
      qualitatively analyzed semi-structured focus group interviews to determine
      attitudes and beliefs about war-related health concerns, symptoms, and health
      care quality. RESULTS: Focus groups revealed important insights about provider
      and patient perspectives of communication and care in four general areas:
      physician-patient trust, validity of symptoms and concerns, exchange of health
      information, and barriers to care. CONCLUSION: Provider-patient communication
      contributes to patient satisfaction with medical care; poor communication may
      contribute to decreased patient satisfaction and provider effectiveness. The
      military health care system poses several challenges to provider-patient
      communication: the dual nature of the provider's role, the occupational
      relationship between illness and health care, pre- and post-deployment issues,
      and continuity of care impact patient and provider perspectives. The prevalence
      of various beneficiary and provider concerns regarding health care communication
      requires further study, particularly for the severely wounded. PRACTICE
      IMPLICATIONS: The quality of information exchanged and of the interpersonal
      relationship impact medical decision making, particularly in occupational health
      settings such as the military. Attention to these issues may improve patient
      outcomes including satisfaction, adherence, trust, health status, and quality of
      life.

PMID- 17537613
TI  - Publication trends in individual anxiety disorders: 1980-2015.
AB  - The aim of the current study was to examine trends in anxiety disorder
      publication over the past 25 years, and to project likely future trends from
      these. Medline searches were used to find a representative sample of the total
      number of journal articles published each year from 1980 to 2005 that were
      focused on each particular anxiety disorder. Results demonstrated that anxiety
      disorder research continued to grow over the 25-year period examined. Growth was
      particularly strong for OCD and PTSD, with strong research growth in panic
      disorder also in the 1980s. Only specific phobia and agoraphobia did not grow in
      research output over the review period. Growth is projected to continue over the
      next 10 years.

PMID- 17537615
TI  - Differential degradation of oak (Quercus petraea) leaf litter by litter
      decomposing basidiomycetes.
AB  - Due to production of lignocellulose-degrading enzymes, saprotrophic litter
      decomposing basidiomycetes can significantly contribute to the turnover of soil
      organic matter. The production of lignin and polysaccharide-degrading enzymes and
      changes in the chemical composition of litter was studied with Marasmius
      quercophilus, Mycena inclinata and Pholiota lenta, three basidiomycete species
      typical of oak (Quercus petraea) forests. Within 12weeks of incubation, M.
      inclinata decomposed 33%, M. quercophilus 36% and P. lenta 48% of the substrate
      dry mass. All fungi produced laccase and Mn-peroxidase and none of them produced
      lignin peroxidase or Mn-independent peroxidases. M. inclinata and M. quercophilus
      produced considerable laccase activity, while production by P. lenta was low. M.
      quercophilus and P. lenta produced most Mn-peroxidase at the beginning of the
      experiment, while the production by M. inclinata was more stable in time. Endo
      1,4-beta-xylanase exhibited the highest activity among endocleaving glycosyl
      hydrolases while 1,4-beta-glucosidase was the main exocleaving enzyme. All fungi
      decreased the C:N ratio of the litter from 27 to 13-17 and M. inclinata and M.
      quercophilus also decreased the lignin content. Analytical pyrolysis of decayed
      litter showed changes in litter composition similar to those caused by white-rot
      fungi during wood decay, e.g. a decrease in the syringyl/guaiacyl lignin ratio.
      These changes were more pronounced in M. inclinata and M. quercophilus. The
      results indicate that different litter-decomposing fungi can cause substantial
      litter transformation despite considerable differences in the production of
      lignocellulose-degrading enzymes.

PMID- 17537614
TI  - Protein kinase Cepsilon makes the life and death decision.
AB  - Cancer is caused by dysregulation in cellular signaling systems that control cell
      proliferation, differentiation and cell death. Protein kinase C (PKC), a family
      of serine/threonine kinases, plays an important role in the growth factor signal
      transduction pathway. PKCepsilon, however, is the only PKCepsilon isozyme that
      has been considered as an oncogene. It can contribute to malignancy by enhancing
      cell proliferation or by inhibiting cell death. This review focuses on how
      PKCepsilon collaborates with other signaling pathways, such as Ras/Raf/ERK and
      Akt, to regulate cell survival and cell death. We have also discussed how
      PKCepsilon mediates its antiapoptotic signal by altering the level or function of
      pro- and antiapoptotic Bcl-2 family members.

PMID- 17537616
TI  - High-resolution solid-state NMR spectroscopy as a tool for investigation of
      enantioselective inclusion complexation.
AB  - In this paper, we showed the application of solid state-NMR (SS NMR) spectroscopy
      in structural studies of chiral compounds employing sample of (E)-1
      diphenylphosphinoylpent-3-en-2-ol 1 as a model compound. Racemate of 1 was fully
      characterized by NMR techniques (both in liquid and solid phase) and X-ray
      crystallography. Theoretical calculations employing the GIAO approach were used
      to explain the influence of hydrogen bonding on 31P NMR shielding parameter in
      racemate. Enantioselective inclusion complexation (EIC) method with TADDOL as
      host molecule was applied to separate of enantiomers. The formation of host-guest
      complex and decomplexation procedure was monitored by means of the SS NMR. The
      liquid-state NMR, due to similarity of 13C and 31P spectral parameters was not
      able to distinguish racemate from enantiomer. In the solid phase, owing to
      distinction of hydrogen bonding and molecular packing in the crystal lattice,
      racemate and enantiomers were easy recognized by NMR spectroscopy.

PMID- 17537617
TI  - Indirect covariance NMR spectroscopy of through-bond homo-nuclear correlations
      for quadrupolar nuclei in solids under high-resolution.
AB  - Indirect covariance NMR spectroscopy is demonstrated in solids, and we show that
      it can be used to obtain through-bond 2D homo-nuclear correlation spectra for
      quadrupolar nuclei under high-resolution. These spectra, generated with indirect
      covariance from a hetero-nuclear correlation spectrum, are equivalent to those
      recorded with the through-bond homo-nuclear hetero-nuclear single-quantum
      correlation (H-HSQC) method very recently proposed. However, the indirect
      covariance method can save a lot of experiment time, compared to the H-HSQC
      experiments, which allows introducing a high-resolution quadrupolar filter, thus
      providing a much better resolution, even on medium-field spectrometers. The
      covariance concept can be used to generate many different "indirectly-detected"
      high-resolution homo-nuclear correlation spectra with through-space or through
      bond correlations for spin 1/2 or quadrupolar nuclei. We also propose a simple
      method that decreases the noise in all (direct or indirect) covariance methods.

PMID- 17537618
TI  - Kinetic adhesion of bacterial cells to sand: cell surface properties and adhesion
      rate.
AB  - Correlation between microbial surface thermodynamics using the extended DLVO
      (XDLVO) theory and kinetic adhesion of various bacterial cells to sand was
      investigated. Two experimental setups were utilized. Adhesion tests were
      conducted in batch reactors with slow agitation. Also, bacteria were circulated
      through small sand columns in a closed loop and the results were analyzed with a
      simple model which accounted for the rate of the adhesion phenomena (omega in h(
      1)) and adhesion percentage. Cells surface properties were derived from contact
      angle measurements. The wicking method was utilized to characterize the sand.
      Zeta potentials were measured for the sand and the cells. Kinetic of bacterial
      retention by the porous media was largely influenced by the electrostatic
      interactions which are correlated with omega from the model (R(2)=0.71). Negative
      zeta potentials resulted in electrostatic repulsions occurring between the sand
      and the bacterial cells which in result delayed bacterial adhesion. While no
      correlation was found between the adhesion percentage and the total interaction
      energy calculated with the XDLVO theory the respective behavior of hydrophobic
      and hydrophilic bacteria as well as the importance of electrostatic interactions
      was evidenced. All the bacterial strains studied adhered more in the column
      experiments than in the adhesion tests, presumably due to enhanced collision
      efficiency and wedging in porous media, while filtration could be ignored except
      for the larger Bacillus strains. Approximate XDLVO calculations due to solid
      surface nanoscale roughness, retention in a secondary minimum and population
      heterogeneity are discussed. Our results obtained with a large variety of
      different physicochemical bacterial strains highlights the influence of both
      surface thermodynamics and porous media related effects as well as the limits of
      using the XDLVO theory for evaluating bacterial retention through porous media.

PMID- 17537619
TI  - [Chest wall lipoblastoma in an 11-month-old girl].

PMID- 17537620
TI  - Technological advances in radioimmunotherapy.
AB  - Radioimmunotherapy (RIT) is a method of selectively delivering radionuclides with
      toxic emissions to cancer cells, while reducing the dose to normal tissues.
      Although primary tumours can often be treated successfully with external beam
      radiotherapy or surgery, metastases often escape detection and treatment, leading
      to therapy failure, and these can be treated with systemic targeted therapies
      such as RIT. This review describes more recent developments in the field,
      including both technological developments from the laboratory and increasingly
      encouraging findings from clinical studies.

PMID- 17537621
TI  - Epidermal growth factor receptor double activating mutations involving both exons
      19 and 21 exist in Chinese non-small cell lung cancer patients.
AB  - AIMS: It has been shown that the introduction of a second mutation into the
      already mutated epidermal growth factor receptor (EGFR) in non-small cell lung
      cancer (NSCLC) will alter the sensitivity to tyrosine kinase inhibitors (TKIs).
      EGFR double activating mutations involving both exons 19 and 21 were previously
      detected in Asian patients, but the sensitivity to TKIs had not yet been
      characterised. Our objective was to profile the status of EGFR double mutations
      in Chinese NSCLC patients and to further ascertain the biological properties.
      MATERIALS AND METHODS: In total, 145 NSCLC tumour samples from unselected Chinese
      NSCLC patients were sequenced to screen mutations in exons 18, 19 and 21 of EGFR.
      Five patients were detected to harbour the delE746-A750+L858R double activating
      mutations. Subcloning experiments were carried out, expression vectors inserted
      with corresponding full-length EGFR were constructed, and in vitro transient
      transfections were performed in 293T cells. Whole cell lysates were collected to
      assess the sensitivity to TKIs using immunoblotting. RESULTS: All five patients
      had adenocarcinoma. The frequency of double mutations was 3.4% (5/145). Three
      patients received and responded to gefitinib treatment. Subcloning experiments
      showed that all the subclones were either wild type or double mutated. At a
      concentration of TKIs of 0.1 microM, the autophosphorylation of the double mutant
      was inhibited greater than that of either single mutated EGFR. However, the
      difference disappeared when the concentration increased to 1 microM. CONCLUSIONS:
      delE746-A750+L858R double activating EGFR mutations exist in Chinese NSCLC
      patients and both locate on the same allele. These patients tend to respond well
      to TKIs and the sensitivity to TKIs of this double mutated EGFR is enhanced
      compared with either single mutant. Nonetheless, the alteration in downstream
      signal transduction of the double mutant remains to be determined.

PMID- 17537622
TI  - Comparison of stratum corneum penetration and localization of a lipophilic model
      drug applied in an o/w microemulsion and an amphiphilic cream.
AB  - Vehicle dependent effects on the penetration behavior of drugs following topical
      application are well known from the literature. In this context, many reports
      concerning the enhancing activities for hydrophilic as well as lipophilic
      substances by colloidal drug carrier systems, particularly microemulsions, are
      available. However, there is little knowledge about the localization of the drugs
      within the skin and the stratum corneum, respectively. In the present study, the
      lipophilic dye curcumin incorporated in an oil-in-water microemulsion and in an
      amphiphilic cream was applied onto the skin of human volunteers. Using the method
      of tape stripping to remove the stratum corneum (SC), the depth profiles of the
      dye within the horny layer were compared. Applying the microemulsion, a deeper
      part of the SC was accessible by a number of 20 tapes removed and significantly
      smaller amounts of curcumin were found on the skin surface. Also differences in
      the distribution and localization of the dye within the stratum corneum were
      observed by laser scanning microscopy. Furthermore, curcumin was detected in hair
      follicles. It was obvious that the microemulsion led to a penetration into the
      complete follicular infundibula, whereas, following application of the cream, a
      fluorescence signal was only received from the follicular orifices.

PMID- 17537623
TI  - Physical gels of a carboxymethyl derivative of scleroglucan: synthesis and
      characterization.
AB  - A carboxymethyl derivative of scleroglucan (Scl-CM) was synthesized and
      characterized through FT-IR, 1H NMR and potentiometer titration. Rheological
      studies allowed evidencing the effect produced by the introduction of the
      carboxymethyl moiety on the native polymer. The mechanical spectrum of the
      scleroglucan solution showed a weak gel behaviour, while the derivative one
      looked like a system near the gel point, that evolved to a gel state depending on
      the concentration. This difference could be related to conformational changes due
      to the introduction of the negative charges on the chains. Different
      concentrations of Ca2+, added to the aqueous solutions of Scl-CM, were able to
      deeply modify the resulting system, showing a sharp transition toward a gel like
      behaviour. Acyclovir was loaded into the hydrogels obtained with different
      amounts of polymer and salt. The release rate of the drug from these systems was
      strictly related to both concentrations of salt and polymer. The obtained results
      suggest a possible employment of these new hydrogels for topical formulations or
      in situ implantation.

PMID- 17537624
TI  - Dry powder inhalation of hemin to induce heme oxygenase expression in the lung.
AB  - The purpose of this study was to formulate hemin as a powder for inhalation and
      to show proof of concept of heme oxygenase 1 (HO-1) expression in the lungs of
      mice by inhalation of hemin. Hemin was spray dried from a neutralized sodium
      hydroxide solution. The particle size distribution of the powder was between 1
      and 5 microm. Dispersion from the Twincer dry powder inhaler showed a fine
      particle fraction (<5 microm) of 36%. A specially designed aerosol box based on
      the Twincer-inhaler was used for a proof of concept study of HO-1 induction by
      inhalation of hemin in mice. The aerosol in the exposure chamber of the aerosol
      box remained aerosolized up to 5 min. A rhodamin B containing aerosol was used to
      show that the aerosol box gave deposition over the entire lung indicating the
      suitability of the model. Additionally, inhalation of hemin showed a dose
      dependent increase in HO-1 protein expression in the lungs. In conclusion, hemin
      was successfully formulated as a powder for inhalation and the inhalation model
      allowed controlled HO-1 expression in the lungs of mice. Future studies
      investigating the utility of inhaled hemin in treating disease states are
      warranted.

PMID- 17537625
TI  - Immediate release of poorly soluble drugs from starch-based pellets prepared via
      extrusion/spheronisation.
AB  - The aim of this study was to evaluate modified starch (high-amylose, crystalline
      and resistant starch) as the main excipient for immediate-release pellets
      containing poorly soluble drugs (hydrochlorothiazide and piroxicam) and prepared
      via extrusion/spheronisation. The bioavailability of pellets (containing 50 mg
      hydrochlorothiazide) was determined after oral administration to 6 dogs. A 2(4)
      factorial design with central point was used to evaluate the influence of
      hydrochlorothiazide (10% and 50%, w/w), HPMC (binder, 4% and 7%, w/w), sorbitol
      (0% and 10%, w/w) and water (granulation liquid, low and high level) on pellet
      yield, size (Feret mean diameter) and sphericity (aspect ratio and two
      dimensional shape factor, eR). Optimal granulation liquid content depended on
      drug and sorbitol level in the formulation. All factors except sorbitol content,
      as well as the interactions between drug concentration and binder level and
      between drug and water level, were significant (P<0.05) for pellet yield, while a
      significant curvature (P<0.05) suggested non-linearity of the response plots. The
      model was not significant for pellet shape, while hydrochlorothiazide and water
      level as well as their interaction were significant (P<0.05) for pellet size.
      Pellet friability, disintegration, residual water content and in-vitro drug
      release were determined. Pellets containing 2.5% (w/w) piroxicam were also
      evaluated. For both model drugs, pellets with a high yield (>90%), acceptable
      sphericity (AR<1.2) and low friability (<0.01%) were obtained. Due to pellet
      disintegration, fast dissolution of both hydrochlorothiazide and piroxicam was
      achieved: >80% drug released in 30 min. The bioavailability (AUC0-->24 h, Cmax
      and tmax) of hydrochlorothiazide pellets in dogs was not significantly different
      from fast-disintegrating immediate-release hydrochlorothiazide tablets (P>0.05).

PMID- 17537626
TI  - Quaternary ammonium functionalized clay film electrodes modified with polyphenol
      oxidase for the sensitive detection of catechol.
AB  - Naturally occurring Cameroonian smectite clay has been grafted with
      trimethylpropylammonium (TMPA) groups and the resulting organoclay has been
      deposited onto a glassy carbon electrode surface as a suitable immobilization
      matrix for polyphenol oxidase (PPO). High sensitivity of the electrochemical
      device to catechol biosensing can be achieved when the enzyme was impregnated
      within the organoclay film subsequent to its deposition due to favorable
      electrostatic interaction between PPO and the TMPA-clay layer. The bioelectrode
      preparation method was also compatible with the use of a mediator (i.e.,
      ferrocene) and the best performance was obtained with a three-layer configuration
      made of glassy carbon coated with a first layer of ferrocene (Fc), which was then
      covered with the PPO-impregnated TMPA-clay layer, and finally overcoated with an
      enzyme-free TMPA-clay film acting as a protecting overlayer to avoid leaching of
      the biomolecule in solution. The electrochemical behavior of the modified film
      electrodes was first characterized by cyclic voltammetry and, then, they were
      evaluated for the amperometric biosensing of the model analyte catechol in batch
      conditions and in flow injection analysis. Various experimental parameters likely
      to influence the biosensor response have been investigated, including the
      electrode preparation mode (composition configuration, thickness), the usefulness
      of a mediator, the operating potential and pH of the medium, as well as the
      advantageous features of the TMPA-clay in comparison to related film electrodes
      based on non-functionalized clays. The organoclay was found to provide a
      favorable environment to enzyme activity and the multilayer configuration of the
      film electrode to provide a biosensor with good characteristics, such as an
      extended linear range for catechol detection (2 x 10(-8) to 1.2 x 10(-5)M) and a
      detection limit in the nanomolar range (9 x 10(-9)M).

PMID- 17537627
TI  - Production of fuel ethanol at high temperature from sugar cane juice by a newly
      isolated Kluyveromyces marxianus.
AB  - Kluyveromyces marxianus DMKU 3-1042, isolated by an enrichment technique in a
      sugar cane juice medium supplemented with 4% (w/v) ethanol at 35 degrees C,
      produced high concentrations of ethanol at both 40 and 45 degrees C. Ethanol
      production by this strain in shaking flask cultivation in sugar cane juice media
      at 37 degrees C was highest in a medium containing 22% total sugars, 0.05%
      (NH(4))(2)SO(4), 0.05% KH(2)PO(4), and 0.15% MgSO(4).7H(2)O and having a pH of
      5.0; the ethanol concentration reached 8.7% (w/v), productivity 1.45 g/l/h and
      yield 77.5% of theoretical yield. At 40 degrees C, a maximal ethanol
      concentration of 6.78% (w/v), a productivity of 1.13 and a yield 60.4% of
      theoretical yield were obtained from the same medium, except that the pH was
      adjusted to 5.5. In a study on ethanol production in a 5l jar fermenter with an
      agitation speed of 300 rpm and an aeration rate of 0.2 vvm throughout the
      fermentation, K. marxianus DMKU 3-1042 yielded a final ethanol concentration of
      6.43% (w/v), a productivity of 1.3g/l/h and a yield of 57.1% of theoretical
      yield.

PMID- 17537628
TI  - Synthesis and antiviral property of allophenylnorstatine-based HIV protease
      inhibitors incorporating D-cysteine derivatives as P2/P3 moieties.
AB  - We designed several HIV protease inhibitors with various d-cysteine derivatives
      as P(2)/P(3) moieties based on the structure of clinical drug candidate, KNI-764.
      Herein, we report their synthesis, HIV protease inhibitory activity, HIV IIIB
      cell inhibitory activity, cellular toxicity, and inhibitory activity against drug
      resistant HIV strains. KNI-1931 showed distinct selectivity against HIV proteases
      and high potency against drug-resistant strains, surpassing those of Ritonavir
      and Nelfinavir.

PMID- 17537629
TI  - Aqua mediated synthesis of substituted 2-amino-4H-chromenes catalyzed by green
      and reusable Preyssler heteropolyacid.
AB  - A simple, clean and environmentally benign route to the synthesis of 2-amino-4H
      chromenes is described using Preyssler type heteropolyacid,
      H(14)[NaP(5)W(30)O(110)], as a green and reusable catalyst in water. The products
      were obtained in very good yields.

PMID- 17537631
TI  - Novel homozygous mutation of the caveolin-3 gene in rippling muscle disease with
      extraocular muscle paresis.
AB  - We describe a 39-year-old Japanese man with rippling muscle disease who carried a
      novel homozygous mutation (Trp70 to a stop codon) in the caveolin-3 gene. The
      patient also had extraocular muscle paresis showing atrophy of the extraocular
      muscles on orbital MRI. The involvement of the extraocular muscles of patients
      with caveolinopathy is discussed.

PMID- 17537630
TI  - Myofiber size correlates with MTM1 mutation type and outcome in X-linked
      myotubular myopathy.
AB  - We aimed to correlate pathologic findings with MTM1 mutation type in a series of
      molecularly defined XLMTM cases. Clinical data from 15 XLMTM patients and their
      corresponding 16 muscle biopsies were studied. All patients were infants (range:
      6-217 days old) when initially biopsied. The proportion of myofibers with central
      nuclei did not correlate with clinical outcome, however, morphometric studies
      showed that survivors had larger myofiber diameters in infancy than those who
      died (10.4+/-3.9microm versus 8.9+/-3microm; p<0.001). As a corollary, patients
      with MTM1 missense mutations had larger myofiber diameters (11.1+/-4microm), than
      those with truncation/deletion mutations (8.6+/-2.7microm) (controls 11.7+/
      2.5microm) (p<0.0001). These data indicate that differences in myofiber size
      correlate with MTM1 mutation type and patient outcome. Failure to attain and/or
      maintain myofiber size, along with fiber type perturbations and the misplacement
      of myofiber nuclei and other organelles, are important components of XLMTM muscle
      pathology.

PMID- 17537632
TI  - Characterization of dystrophic muscle in golden retriever muscular dystrophy dogs
      by nuclear magnetic resonance imaging.
AB  - The Golden Retriever Muscular Dystrophy dog lacks dystrophin. Disease progression
      in this model shares many similarities with the Duchenne muscular dystrophy, both
      from anatomico pathological and clinical standpoints. The model is increasingly
      used in pre-clinical trials but needs to be further investigated, particularly
      with reference to the evaluation of therapies. The aim of this study was to
      identify quantitative indices that would help characterize the dystrophic dog non
      invasively using NMR imaging. Two-month-old dystrophic dogs and healthy control
      animals were scanned at 4T. Standard T2- and T1-weighted images, fat-saturated T1
      weighted images pre- and post-gadolinium chelate injection were acquired and
      kinetics of muscle enhancement were studied over a 2-h period. Several indices
      were found to be abnormally high in dystrophic dogs: the T2-weighted/T1-weighted
      signal ratio, T2-weighted image heterogeneity and maximal signal enhancement post
      gadolinium. These may be proposed to evaluate muscle structural alterations non
      invasively in this disease.

PMID- 17537633
TI  - Myopathy associated with statin therapy.

PMID- 17537634
TI  - Isokinetic muscle testing for weak patients suffering from neuromuscular
      disorders: a reliability study.
AB  - Precise, sensitive muscle strength testing methods are needed to investigate
      muscle function in patients with neuromuscular disorders (NMD). Here, we describe
      an isokinetic knee flexor and extensor testing procedure using the Biodex 3's
      continuous passive motion (CPM) mode. The torque values recorded during passive
      isokinetic motion were subtracted from the torque values obtained for the same
      movement with maximal, concentric effort. The aims of the present study were to
      (i) evaluate the method's reliability in NMD patients presenting mild to severe
      muscle weakness and (ii) study the relationship between manual muscle testing
      (MMT) and isokinetic dynamometry. The fifteen participating patients were tested
      twice; the respective intraclass correlation coefficients (ICCs) for the two
      sessions ranged from 0.91 to 0.99 for the peak torque, work and power and from
      0.50 to 0.90 for the angle at peak torque. The Spearman rho correlation
      coefficients comparing isokinetic values and MMT values ranged from 0.67 to 0.74
      (p<0.01). This reliable, dynamic method appears to be of great value in NMD
      evaluation when sensitive strength measurement at the knee is required.

PMID- 17537635
TI  - Quantitative skeletal muscle ultrasound: diagnostic value in childhood
      neuromuscular disease.
AB  - In this study we investigated the diagnostic value of quantitative skeletal
      muscle ultrasonography in 150 consecutively referred children with symptoms
      suspect for a neuromuscular disorder. Muscle thickness and quantitatively
      determined echo intensity of four muscles and the distribution of these variables
      within the body were examined. RESULTS: Patients with and without a neuromuscular
      disorder could be discriminated with a positive predictive value of 91% and a
      negative predictive value of 86%. Patients with a neurogenic disorder could be
      distinguished from myopathies and non-neuromuscular disorders with a positive
      predictive value of 86% and a negative predictive of 84%, using the pattern of
      distribution of pathology within the body. CONCLUSIONS: Skeletal muscle
      ultrasound is a good, practical and non-invasive aid in the diagnosis of
      neuromuscular disorders in children, that is able to discriminate between
      children with and without a neuromuscular disorder and between neurogenic
      disorders and myopathies with high predictive values.

PMID- 17537636
TI  - Variable penetrance of COL6A1 null mutations: implications for prenatal diagnosis
      and genetic counselling in Ullrich congenital muscular dystrophy families.
AB  - Collagen VI mutations cause mild Bethlem myopathy and severe, progressive Ullrich
      congenital muscular dystrophy (UCMD). We identified a novel homozygous COL6A1
      premature termination mutation in a UCMD patient that causes nonsense-mediated
      mRNA decay. Collagen VI microfibrils cannot be detected in muscle or fibroblasts.
      The parents are heterozygous carriers of the mutation and their fibroblasts
      produce reduced amounts of collagen VI. The molecular findings in the parents are
      analogous to those reported for a heterozygous COL6A1 premature termination
      mutation that causes Bethlem myopathy. However, the parents of our UCMD proband
      are clinically normal. The proband's brother, also a carrier, has clinical
      features consistent with a mild collagen VI phenotype. Following a request for
      prenatal diagnosis in a subsequent pregnancy we found the fetus was a
      heterozygous carrier indicating that it would not be affected with severe UCMD.
      COL6A1 premature termination mutations exhibit variable penetrance necessitating
      a cautious approach to genetic counselling.

PMID- 17537637
TI  - Sensitivity and specificity of qualitative muscle ultrasound in assessment of
      suspected neuromuscular disease in childhood.
AB  - Muscle ultrasound is considered a useful noninvasive technique for visualizing
      normal and pathological skeletal muscle. We determined the accuracy of
      qualitative muscle ultrasound in the discrimination of normal muscle from
      myopathic, neurogenic, and unspecifically abnormal tissue changes in the
      evaluation of suspected NMD in childhood. Sensitivity and specificity of muscle
      ultrasound were assessed by comparing sonographic classification of muscle tissue
      changes in 134 children with definitive diagnosis as provided by muscle histology
      or mutation analysis performed subsequently to the sonography. We found a
      sensitivity of 81% and a specificity of 96% for detection of any abnormal muscle
      tissue alteration by ultrasound. For detection of neurogenic changes, sensitivity
      was 77% with even higher specificity (98%). Accuracy was slightly lower for
      myopathic changes (79%) and clearly lower for unspecific abnormal tissue
      alterations (70%). Accuracy of ultrasound was lower in younger children. High
      reliability of muscle sonography justifies a more widespread use of this method
      in evaluation of suspected NMD in childhood.

PMID- 17537638
TI  - The intracellular cyanobacteria of Paulinella chromatophora: endosymbionts or
      organelles?
AB  - Endosymbiotic relationships are common across the tree of life and have had
      profound impacts on cellular evolution and diversity. Recent molecular
      investigations of the amoeba Paulinella chromatophora have raised a timely and
      important question: should obligatory intracellular cyanobacteria in Paulinella
      be considered new organelles, or do plastids and mitochondria hold a unique
      stature in the history of endosymbiotic events? We argue that drawing a sharp
      distinction between these two organelles and all other endosymbionts is not
      supported by accumulating data, neither is it a productive framework for
      investigating organelle evolution.

PMID- 17537639
TI  - Effects of gamma radiation on maize samples contaminated with Fusarium
      verticillioides.
AB  - The efficacy of gamma-irradiation as a method of decontamination of maize
      containing Fusarium verticillioides under controlled conditions of relative
      humidity (RH) (97.5%) and water activity has been studied. Maize grains
      inoculated with a spore suspension of F. verticillioides were irradiated to 2, 5,
      and 10 kGy. Thereafter, the irradiated and control samples were analyzed for the
      presence of fumonisins, their viable cells were counted, and their morphology was
      investigated by electronic microscopy. It was found possible to decrease the risk
      of exposure to fumonisins by irradiating maize to 5 or 10 kGy. However, at the
      dose of 2 kGy, the survived fungi (36%) can produce more fumonisins than the
      fungi in the control unirradiated samples under the same conditions.

PMID- 17537640
TI  - Forster energy transfer from nonexponentially decaying donors.
AB  - Necessary modifications to the expression for the Forster energy transfer rate
      are discussed when fluorescence decay of the donor in the absence of acceptor is
      nonexponential. Discrete and continuous models of the nonexponentiality are taken
      into account. No general solution of the problem is found. It is, however,
      suggested that in many of the biochemical problems the most appropriate
      modification of the transfer rate can be that which is based on the assumption of
      the same constant value of the radiative decay rate for all donor molecules. The
      effect of the assumed form of the Forster energy transfer rate on the recovered
      values of the distance distribution and dynamics parameters of some exemplary
      bichromophoric systems is examined.

PMID- 17537641
TI  - Guanine-specific DNA oxidation photosensitized by the tetraphenylporphyrin
      phosphorus(V) complex via singlet oxygen generation and electron transfer.
AB  - The photosensitized DNA damage caused by dihydroxoP(V)tetraphenylporphyrin
      (P(V)TPP), a cationic water-soluble porphyrin, was examined. The study of near
      infrared emission measurements demonstrated the photosensitized singlet oxygen
      ((1)O(2)) generation by P(V)TPP (quantum yield: 0.28 in ethanol). The
      fluorescence quenching of P(V)TPP by DNA showed the electron transfer (ET) from
      nucleobases to photoexcited P(V)TPP. These results have shown that P(V)TPP has
      ability to damage DNA through dual mechanisms, (1)O(2) generation and ET. Under
      aerobic conditions, P(V)TPP photosensitized damage was more severe for single
      stranded DNA compared to its double-stranded counterpart. Photoexcited P(V)TPP
      damaged every guanine residue in single-stranded DNA. HPLC measurements confirmed
      the formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo), an oxidized
      product of 2'-deoxyguanosine, and showed that the yield of 8-oxodGuo in single
      stranded DNA is larger than that in double-stranded DNA. The guanine-specific DNA
      damage and the enhancement in single-stranded DNA suggest that the (1)O(2)
      generation mainly contributes to the mechanism of DNA photodamage by P(V)TPP.
      Absorption spectrum measurements suggested the interaction between P(V)TPP and
      DNA. This interaction is expected to enhance the (1)O(2)-mediated DNA damage
      since the lifetime of (1)O(2) is very short. On the other hand, for double
      stranded DNA, photosensitized damage at consecutive guanines was much less
      pronounced. Because the consecutive guanines act as a hole trap, this DNA
      damaging pattern suggests the partial involvement of photoinduced ET. However,
      DNA damage by ET was not a main mechanism, possibly due to the reverse ET. In
      conclusion, P(V)TPP induces guanine specific photooxidation mainly via (1)O(2)
      generation. The interaction with DNA and the energy level of the photoexcited
      porphyrin may be advantageous for (1)O(2)-mediated DNA damage rather than ET
      mechanism.

PMID- 17537642
TI  - Mechanism study on the origin of delayed fluorescence by an analytic modeling of
      the electronic reflux for photosynthetic electron transport chain.
AB  - A mathematical-physical analysis model, which describes individually the
      electronic reflux of several significant components in the photosynthesis
      electron transport chain, was firstly developed. The process of electrons flowing
      back to the oxidized reaction center P(680)(+) was simulated by a series of
      photochemical reaction equations, resulting in getting the linked differential
      equations of delayed fluorescence (DF) intensity. MATLAB provided a
      computationally efficient method to solve these linked equations. Simulations
      based on this model showed that the decay kinetics of DF accord with double
      exponential. DF components decaying in the millisecond range (fast phase) are
      related to the charge recombination of P(680)(+) and Q(A)(-). The components
      decaying in the seconds range are associated with the recombination of P(680)(+)
      with Q(B)(2-). The developed model was tested in maize leaves treated with
      different electron blockers to induce changes in photosynthesis electron
      transport chain. The experimental results demonstrated that the developed model
      can accurately determine the regulatory effects of electron blockers on
      photosynthesis electron transport chain. Therefore, the model presented here
      could be potentially useful for studying the electron transfer in plant. It also
      provides an experimental workbench for testing hypotheses as to the underlying
      mechanism controlling the change for different phases of DF.

PMID- 17537643
TI  - pH-induced structural transitions of caseins.
AB  - Caseins are relatively small (molecular mass approximately 20 kDa), unstructured
      milk proteins of which the main components are referred to as alpha(s)-, beta-
      and kappa-casein. All three components lack a compact folded conformation, which
      can be ascribed to a combination of their low overall hydrophobicity and high net
      charge. Structural transitions of the three caseins in response to variation of
      pH were investigated using fluorescence and circular dichroism (CD) spectroscopy.
      Tryptophan emission parameters (intensity and wavelength of emission maximum) and
      CD spectra showed that at neutral and alkaline pH the caseins exist predominantly
      in random coil conformation. As the solvent is made acidic the added protons
      compensate the negative charges on the caseins and reduce the repulsion between
      like charged residues, allowing the casein chains to fold. At the pI (pH 4-5),
      the net charge on the protein tends to zero and the protein should approach its
      maximally structured state. Below pI, the uncompensated charges and their
      interactions reappear, resulting in slackening of the compact structure and
      formation of a partially unfolded intermediate. These conclusions were borne out
      by the biphasic pH-dependence of the fluorescence emission parameters of Trp as
      well as of ANS incubated with the caseins. Measurement of the efficiency of
      energy transfer between Trp (donor) and ANS (acceptor) and of the CD spectra of
      caseins as functions of pH were also consistent with this scenario.

PMID- 17537644
TI  - FGF2 effects in periosteal fibroblasts bearing the FGFR2 receptor Pro253 Arg
      mutation.
AB  - AIM: A growing number of mutations mapped in the receptor gene for fibroblast
      growth factor have been implicated in several cranial development disorders
      including the Apert and Crouzon syndromes. The present paper investigated
      cellular mechanisms underlying Apert phenotype, by analyzing the effects of FGF2
      in primary cultures of Apert periosteal fibroblasts carrying the FGFR2 Pro253Arg
      mutation. RESULTS: FGF2 administration significantly decreased extracellular
      matrix production in mutant cells by stimulating degradative enzymatic
      activities. Gene expression analysis revealed that decorin and biglycan, two
      proteoglycans involved in collagen fibrillogenesis, were more expressed in mutant
      cells and down-regulated by FGF2. FGF2 receptor binding showed little differences
      in high affinity receptor counts between mutant and wild-type cells, while we
      showed for the first time that low affinity receptors are significantly fewer in
      mutant cells. Differences were found in Crouzon syndrome, where both high and low
      affinity receptor counts were up-regulated. CONCLUSIONS: The different mutation
      and low affinity receptor regulation in mutant receptors support the hypothesis
      that the impact on the activity of the ligand-receptor complex could allow
      distinct modes of FGF2 activation in Apert and Crouzon syndromes, which interfere
      with the FGFR2 signalling cascade.

PMID- 17537645
TI  - Expression and purification in high yield of a functionally active recombinant
      human Type I inositol(1,4,5)P3 5-phosphatase.
AB  - Inositol polyphosphates are the most widespread second messenger molecules in
      eukaryotic cells. Human Type I inositol 1,4,5-triphosphate (Ins(1,4,5)P(3)) 5
      phosphatase removes the D-5 position phosphate from soluble Ins(1,4,5)P(3,) a key
      event in cell signaling particularly in Ca(2+) homeostasis. In this study, the
      cDNA encoding human Type I Ins(1,4,5)P(3) 5-phosphatase was subcloned into a
      modified pMAL expression vector. This plasmid produces a recombinant protein in
      fusion with affinity tags located at its N-terminus, consisting in a maltose
      binding protein (MPB) and an octa-histidine stretch. The construction was
      transformed into Escherichia coli BL21 (DE3) expression strain. This dual tag
      strategy allows the purification of milligrams of highly purified protein. The
      recombinant human Type I Ins(1,4,5)P(3) 5-phosphatase is active and can thus be
      used for functional and structural studies.

PMID- 17537646
TI  - An improved procedure for expression and purification of ribosomal protection
      protein Tet(O) for high-resolution structural studies.
AB  - Tetracycline (Tc) is a broad spectrum antibiotic that binds to the A site of the
      bacterial ribosome inhibiting delivery of aminoacyl-tRNA to the A site for
      productive protein biosynthesis. Tet(O) is in a class of the ribosomal protection
      proteins (RPPs) found in many pathogenic bacteria, that dislodges Tc from the A
      site of 70S ribosome to restore polypeptide elongation and confer Tc resistance
      to the bacteria. Considerable difficulty has been encountered in overexpressing
      and purifying Tet(O) from various Escherichia coli strains using lambdaPI, tac or
      T7 promoters. Here we report molecular cloning, overexpression of His-tagged
      Tet(O) in E. coli, an improved purification procedure and initial biochemical and
      biophysical characterization of His-tagged Tet(O).

PMID- 17537648
TI  - Longitudinal and cross-sectional analysis of atrophy in Alzheimer's disease:
      cross-validation of BSI, SIENA and SIENAX.
AB  - Brain volume loss (atrophy) is widely used as a marker of disease progression.
      Atrophy has been measured with a variety of methods, some estimating atrophy rate
      from two temporally separated scans, and others estimating atrophy state from a
      single scan. Three popular tools for measuring brain atrophy are BSI and SIENA
      (rate) and SIENAX (state). Previous papers have shown BSI and SIENA to have
      similar accuracy, but no work has carefully compared both methods using the same
      data set. Here we compare these methods, using data from patients with
      Alzheimer's disease and age-matched controls. We also compare the SIENA
      longitudinal measure with atrophy state estimated by SIENAX using just the
      earliest scan taken from each subject. We show strong correspondence and similar
      sensitivity to atrophy between all 3 measures.

PMID- 17537647
TI  - Where left becomes right: a magnetoencephalographic study of sensorimotor
      transformation for antisaccades.
AB  - To perform a saccadic response to a visual stimulus, a 'sensorimotor
      transformation' is required (i.e., transforming stimulus location into a motor
      command). Where in the brain is this accomplished? While previous monkey
      neurophysiology and human fMRI studies examined either parietal cortex or frontal
      eye field, we studied both of these regions simultaneously using
      magnetoencephalography (MEG). Nineteen healthy participants performed a
      pseudorandom series of prosaccades and antisaccades during MEG. Antisaccades
      require a saccade in the direction opposite a suddenly appearing stimulus. We
      exploited this dissociation between stimulus and saccadic direction to identify
      cortical regions that show early activity for a contralateral stimulus and late
      activity for a contralateral saccade. We found that in the left hemisphere both
      the intraparietal sulcus and the frontal eye field showed a pattern of activity
      consistent with sensorimotor transformation - a transition from activity
      reflecting the direction of the stimulus to that representing the saccadic goal.
      These findings suggest that sensorimotor transformation is the product of
      coordinated activity across the intraparietal sulcus and frontal eye field, key
      components of a cortical network for saccadic generation.

PMID- 17537649
TI  - Functional mapping of rat barrel activation following whisker stimulation using
      activity-induced manganese-dependent contrast.
AB  - BACKGROUND: Cortical whisker barrels in the primary somatosensory cortex are a
      well-known example of brain function in rodents. The well-defined relationship
      between barrels and whiskers makes this system a unique model to study neuronal
      function and plasticity. In this study, we sought to establish a feasible working
      protocol of applying manganese-enhanced MRI (MEMRI) to map the cortical barrels
      following whisker stimulation. METHODS: The protocol was based on the principle
      of activity-induced manganese-dependent (AIM) contrast. Rats were prepared by
      sodium pentobarbital anesthetization, intraperitoneal manganese-chloride
      injection, right common carotid mannitol injection and temperature maintenance.
      Left whiskers were connected to a speaker through a cotton thread and were
      stimulated by a series of rectangular pulses. MEMRI was acquired with a 3T
      scanner 3 h after whisker stimulation. Before MR scanning, Wistar rats were
      euthanized to avoid motion artifacts. To improve the signal-to-noise ratio (SNR)
      and detection sensitivity, image coregistration, pixel intensity normalization,
      statistical mapping, group averaging and subtraction were performed. The AIM
      enhancement of the cortical barrels was quantified using volume of interest
      analysis on the acquired T1WI and R1 mapping. RESULTS: Both experimental and
      control groups showed greater enhancement in the right hemisphere, same side as
      mannitol injection. In the experimental group, however, activity-induced
      enhancement was more localized in the right barrel fields, whereas in the control
      group, the enhancement was uniform throughout the right cortex. In the right
      cortical barrels, the enhancement ratios and R1 values in the experimental group
      were significantly higher than those in the control group. In the left cortical
      barrels, there was no significant difference between the two groups. Subtracted
      images and voxel-based statistical t-value mapping between experimental and
      control groups showed additional enhancement concentrated in the right cortical
      barrels. CONCLUSIONS: We have mapped rat whisker barrels using the AIM method and
      have shown a clear relationship between manganese-enhanced cortical regions and
      whisker tactile-sense-evoked activity. It is possible that, with sufficient SNR,
      the AIM method may reach whisker barrel discrimination, potentially useful to
      study plasticity in surgically or genetically manipulated rat brains.

PMID- 17537650
TI  - The effects of radial shock waves on gene transfer in rabbit chondrocytes in
      vitro.
AB  - OBJECTIVE: The purpose of this study was to develop a new technique of gene
      transfer utilizing radial shock waves. The effects of radial shock waves on gene
      transfer in rabbit chondrocytes were examined by varying the parameters of
      exposure conditions in vitro. METHODS: Chondrocytes were obtained from New
      Zealand white rabbits and cultured in a monolayer. A luciferase-encoding gene
      expression vector, or vector alone, was added to chondrocyte cell suspensions,
      and the cells were then exposed to radial shock waves. Parameters such as
      pressure amplitude, number of pulses, frequency, and DNA concentration were
      varied, and luciferase activity was measured 48h after transfection. Transfection
      efficiency of radial shock waves was compared with the FuGENE6 transfection
      method using a green fluorescence protein (GFP)-encoding gene vector by
      fluorescent-activated cell sorter (FACS) analysis. RESULTS: Radial shock wave
      exposure significantly increased luciferase activity over 140-fold as compared to
      the control under the optimal exposure conditions. Both pressure amplitude and
      number of pulses were relevant to transfection efficiency and cell viability, but
      frequency was not. Transfection efficiency increased in a dose-dependent manner
      with DNA concentration. FACS analysis showed 4.74% of GFP-encoding gene using
      radial shock waves. FuGENE6 transfection was almost similar in transfection
      efficiency to radial shock wave. CONCLUSION: In spite of certain degree of cell
      disruption, radial shock waves significantly augmented reporter gene transfection
      in rabbit chondrocytes in vitro. Radial shock waves may potentially contribute to
      the treatment of the cartilage morbidities by enhancing the potency of tissue
      healing and gene transfection of growth factors.

PMID- 17537651
TI  - Rho activation is required for transforming growth factor-beta-induced epithelial
      mesenchymal transition in lens epithelial cells.
AB  - Lens epithelial cells undergo epithelial-mesenchymal transition (EMT) after
      injury as in cataract extraction, leading to fibrosis of the lens capsule. We
      have recently shown that TGF-beta-induced EMT in lens epithelial cells depends on
      PI3 kinase/Akt signal pathway. In this report, we suggest Smad3 is necessary for
      TGF-beta-induced EMT by showing that the expression of dominant-negative Smad3
      blocks the expression of alpha-smooth muscle actin (alpha-SMA) and morphological
      changes. We also show that TGF-beta induces a biphasic change in Rho activity,
      and that Y27632, a selective inhibitor of Rho effector ROCK, inhibits TGF-beta
      induced EMT in vitro and in vivo. We finally show that Smad3 activation and Rho
      signal activation is independent each other. All of these findings suggest that
      Rho/ROCK activation together with Smad3 is necessary for TGF-beta-induced EMT in
      lens epithelial cells.

PMID- 17537652
TI  - Our cells get stressed too! Implications for human disease.
AB  - Significant progress has been made in recent years elucidating the molecular
      controls of cellular responses to DNA damage in mammalian cells. Many of the
      insights that we have gained into the mechanisms involved in cellular DNA damage
      response pathways have come from studies of human cancer susceptibility syndromes
      that are altered in DNA damage responses. ATM, the gene mutated in the cancer
      prone disorder, ataxia telangiectasia, is a protein kinase that is a central
      mediator of responses to DNA double strand breaks in cells. Such insights provide
      us with opportunities to develop new approaches to benefit patients. For example,
      inhibitors of the ATM pathway have the potential to act as sensitizers to
      chemotherapy or radiation therapy and could even have anti-neoplastic effects on
      their own. Conversely, activators of ATM could improve responses to cellular
      stresses such as oxidative damage. The potential benefits of ATM modulation in
      disease settings ranging from metabolic syndrome to cancer will be discussed.

PMID- 17537653
TI  - A case of neonatal dural sinus malformation: clinical symptoms, imaging and
      neuropathological investigations.
AB  - We report a case of neonatal dural sinus malformation already visible on
      antenatal ultrasound. This is a rare disease entity in infants and children.
      Clinical diagnosis was made by demonstrating a cranial murmur on auscultation;
      macrocrania and signs of progressive cardiac failure. Imaging studies as cerebral
      ultrasound, postnatal MRI scan and MR angiography demonstrated a large dural
      sinus malformation originating from the sagittal sinus with extensive
      arteriovenous fistulae. Due to the extent of the lesion, the existing ischemic
      brain damage and involvement of the torcular, no therapeutic options were
      available and the child died of irreversible cardiac failure. The diagnosis was
      confirmed with autopsy. We discuss the clinical presentation, imaging and
      neuropathological results and relate our findings to embryological data and the
      existing literature.

PMID- 17537654
TI  - Effect of inhaled hyaluronic acid (HA) on exercised induced bronchoconstriction
      (EIB).

PMID- 17537655
TI  - Effect of copper on liver key enzymes of anaerobic glucose metabolism from
      freshwater tropical fish Prochilodus lineatus.
AB  - We investigated the effect of copper on liver key enzymes of the anaerobic
      glucose metabolism (hexokinase, HK; phosphofructokinase, PFK; pyruvate kinase,
      PK; lactate dehydrogenase, LDH) as well as of the pentose pathway (glycose-6
      phosphate dehydrogenase, G6PDH) from the fish Prochilodus lineatus. The fish were
      acclimated at either 20 degrees C or 30 degrees C at pH 7.0, transferred to water
      at pH 4.5 or 8.0, and exposed to 96 h-CL(50) copper concentrations. Copper
      accumulation in liver was higher in fish acclimated at 20 degrees C and
      maintained in water pH 8.0. Three-way analysis of variance revealed a significant
      effect of temperature on all enzymes, a significant effect of pH on all enzymes
      except for PK, and a significant effect of copper on only PFK, and LDH in pH 4.5
      at 20 degrees C and, at 30 degrees C, on PFK and PK at pH 4.5 and 8.0, HK at pH
      4.5 and G6PDH at pH 8.0. There were significant interactions between treatments
      for many enzymes. These changes suggest that the activity of enzymes in question
      is modified by a change in ambient water. At least at 30 degrees C, the overall
      reduction in the glycolytic enzyme activities of copper-exposed fish seems to
      reduce energy availability via glucose metabolism, thereby contributing to
      enhance copper toxic effects.

PMID- 17537656
TI  - Molecular characterization of neuropeptide Y gene in Chinese perch, an
      acanthomorph fish.
AB  - The full-length neuropeptide Y (NPY) cDNA of Chinese perch Siniperca chuatsi was
      704 bp in length, and contained a 300 bp open reading frame encoding a prepro-NPY
      with 99 amino acids. The predicted prepro-NPY peptide contained a putative signal
      peptide of 28 amino acids and a mature NPY of 36 amino acids, followed by the
      proteolytic processing site Gly-Lys-Arg and 35 amino acids that comprise the C
      terminal peptide of NPY. Amino acid alignment and phylogenetic analysis indicate
      that the predicted Chinese perch prepro-NPY (composed of 99 amino acids) had high
      identities to the prepro-NPY of acanthomorph fishes (93-95%), whereas it had much
      lower identities to the prepro-NPY (composed of 96 or 97 amino acids) of cyprinid
      fishes (59-60%) or mammals (57-63%). Chinese perch NPY gene consists of four
      exons and three introns. The ratio of intron 2 to intron 3 was over 14 in Chinese
      perch NPY gene, whereas this ratio was below 4 in zebrafish and mammalian NPY
      gene. The total size of the Chinese perch NPY gene was 2223 bp, which was only
      about 28% of the size of NPY gene in higher vertebrate. Analysis of a 1622 bp
      promoter region of Chinese perch NPY gene, revealed a typical TATA box, a GC box
      and an untypical CAAT box, located at 84 bp, 101 bp and 303 bp upstream of the
      start codon respectively. Three STAT binding site-like elements (TCCAGTA) which
      were necessary for the leptin-induced transcriptional control of rat NPY gene
      were identified. In consistence to the effect of cortisol on fish brain NPY mRNA
      expression, four glucocorticoid-responsive elements were detected. Besides the
      highest expression in brain, substantial level of Chinese perch NPY mRNA
      expression was detected in the spleen and liver, and trace level of NPY mRNA
      expression was also detected in the adipose tissue, intestine and muscle. These
      results indicated that Chinese perch NPY might be involved in the food intake
      control by leptin and cortisol system, and diversification of NPY signaling
      should exist between acanthomorph fishes and cyprinid fishes as well as mammals.

PMID- 17537657
TI  - Expression of a cDNA encoding a member of the hexamerin storage proteins from the
      moth Sesamia nonagrioides (Lef.) during diapause.
AB  - We isolated and sequenced a cDNA clone corresponding to a storage protein
      (SnoSP1) from the corn stalk borer Sesamia nonagrioides (Lef.). The cDNA for
      SnoSP1 (2403 bp) codes for a 751 residue protein with predicted molecular mass of
      88.3 kDa and calculated isoelectric point pI=8.72. A signal peptide of 16 amino
      acids is present at the N-terminus and the protein contained conserved insect
      larval storage protein signature sequence patterns. Multiple alignment analysis
      of the amino acid sequence revealed that SnoSP1 is most similar to the basic
      juvenile hormone-suppressible protein 2 precursor (TniSP2) from Trichoplusia ni
      (71% identity) and other moderately methionine-rich hexamers. According to both
      phylogenetic analyses and the criteria of amino acid composition, SnoSP1 belongs
      to the subfamily of moderately methionine-rich storage proteins (3.7% methionine,
      11% aromatic amino acid). Treatment with the juvenile hormone analog,
      methroprene, after head ligation of larvae, is found to suppress the level of
      SnoSP1 gene, indicating hormonal effects at the transcriptional level. We also
      examined developmental profiles of SnoSP1 expression in fat body from diapausing
      and non-diapausing larvae by semi-quantitative and Real-Time PCR assays. In non
      diapause conditions the abundance of SnoSP1 was found in high levels during the
      last larval stage and decreased gradually during the pupal stage. Very low levels
      of this mRNA were detected in larvae that were preparing to enter diapause, but
      mRNA dramatically increased in those that were in diapause as well as in those
      that terminate diapause.

PMID- 17537658
TI  - GHR exon 3 polymorphism: association with type 2 diabetes mellitus and metabolic
      disorder.
AB  - Growth hormone (GH) signaling via the growth hormone receptor (GHR) forms a major
      part of the GH-IGF-I axis, which is crucial for controlling metabolism and
      anabolism. Two common variants of the GHR differ by the presence (full length or
      GHR(fl)) or absence of exon 3 (exon 3 deleted or GHR(d3)), the function of which
      is unknown. However, differential response to GH treatment has been observed with
      carriers of the GHR(d3) variant conferring a greater growth rate. This study
      investigates these GHR variants in subjects with normal glucose tolerance (NGT)
      and impaired glucose tolerance (IGT), including Type 2 diabetes mellitus (T2DM).
      DNA was extracted from blood samples from subjects with NGT (n=158), IGT (n=116)
      and T2DM (n=194). The T2DM subjects in set 1 (n= 39) were newly diagnosed, whilst
      those in set 2 (n=155) had a mean duration of 7 years. Set 1 also included NGT
      and IGT subjects. Genotyping by standard PCR and gel electrophoresis were carried
      out. A significant difference was observed between T2DM and NGT (p<0.0001) with a
      significantly lower frequency of GHR(d3) in T2DM (3.6% compared to 17% in NGT).
      Both sets of T2DM subjects with at least one GHR(d3) allele had significantly
      higher BMI. In the larger subset of T2DM, GHR(d3) was associated with higher CRP
      levels as well as age adjusted IGF-I, with a trend of higher C-peptide secretion
      and impaired lipid levels, indicating a phenotype with metabolic disorder when
      compared to the GHR(fl/fl) T2DM subjects. In conclusion, homozygosity for the
      GHR(d3) allele appears to be preventive of T2DM. However, when other factors
      cause overt T2DM, the GHR(d3) allele confers a phenotype indicative of metabolic
      disorder. This study supports the hypothesis that the two GHR alleles by their
      inclusion or exclusion of exon 3 are functionally different.

PMID- 17537659
TI  - Mutation analysis a prerequisite for prenatal diagnosis of L-2-hydroxyglutaric
      aciduria?
AB  - The prenatal diagnosis of two subsequent pregnancies of the mother of a patient
      homozygous for a mutation in the L-2-hydroxyglutarate dehydrogenase gene is
      described. In the first pregnancy, measurement of L-2-hydroxyglutaric acid in
      amniotic fluid revealed an affected fetus. This pregnancy was terminated. In the
      prenatal diagnosis of the second pregnancy, mutational analysis was also included
      and proved to be of pivotal importance. Despite mildly increased levels of L-2
      hydroxyglutaric acid in the amniotic fluid, the fetus was heterozygous for this
      mutation thus excluding L-2-HGA.

PMID- 17537660
TI  - The epidemiology of hospitalized pneumonia in rural Kenya: the potential of
      surveillance data in setting public health priorities.
AB  - INTRODUCTION: Surveillance data from inpatient health facilities can be useful
      for prioritization of public health initiatives, but often are not collected or
      analyzed in developing countries. We evaluated data on hospitalized patients
      diagnosed with pneumonia in rural western Kenya to characterize pneumonia
      epidemiology and mortality. METHODS: Data were obtained from admission registers
      of all inpatient facilities from 2001 to 2003 in Bondo District (estimated 2003
      population: 255901), which is holoendemic for malaria and has high HIV rates.
      Inpatients with diagnoses compatible with acute pneumonia were included, and
      census data (1999) were used to calculate incidence rates by age, sex, season,
      and residence. RESULTS: From 2001 to 2003, a total of 2466 patients diagnosed
      with pneumonia were hospitalized with 282 deaths (11.4%). Incidence peaked at 698
      per 100,000 person-years among children <5 years of age. A second peak occurred
      among 20-29 year-olds at 356 per 100,000 person-years; rates were twice as high
      in women as men in this age group (p<0.001). The incidence in persons >65 years
      was 121 per 100,000 person-years. Pneumonia incidence peaked during the twice
      yearly high malaria seasons, 1-2 months after peak rainfall. Rates of pneumonia
      decreased with increasing distance of residence from the district hospital
      (p<0.0001). DISCUSSION: In Bondo District, the pneumonia burden is greatest among
      young children and middle-aged adults, the latter peak reflecting the area's HIV
      epidemic. Access to care likely influenced hospital utilization and thus
      pneumonia rates, particularly among the elderly. Our findings show that hospital
      based data can provide useful information for public health priority setting,
      such as the introduction of new pneumonia vaccines for children and accelerating
      the introduction of antiretroviral medications.

PMID- 17537661
TI  - Molecular epidemiology of methicillin-resistant Staphylococcus aureus isolates
      from regional hospitals in Trinidad and Tobago.
AB  - OBJECTIVES: Methicillin-resistant Staphylococcus aureus (MRSA), first reported in
      a British hospital in the early 1960s, has now reached global proportions.
      Geographic spread of one or several MRSA clones in a city, country, and even
      among countries and continents has been identified by molecular techniques. We
      sought to determine whether clonal spread of MRSA has occurred in Trinidad and
      Tobago from all MRSA isolates collected between 2000 and 2001. METHODS: Clinical
      isolates of MRSA from three major hospitals in Trinidad and Tobago were
      identified by standard laboratory methods and analyzed using multiplex polymerase
      chain reaction (PCR) and pulsed-field gel electrophoresis (PFGE) after SmaI
      digestion. RESULTS: There was a 12.8% prevalence of MRSA in three major regional
      hospitals in Trinidad and Tobago. All 60 randomly selected MRSA strains from
      these hospitals produced similar PFGE banding patterns, suggesting a genetic
      relatedness among strains and that they belonged to a single clonal family. All
      isolates were negative for the Panton-Valentine leukocidin gene (pvl). These
      strains shared a PFGE banding pattern approximately (96%) the same as a Canadian
      strain called CMRSA-6 in the Canadian National Microbiology Laboratory database.
      CONCLUSIONS: We conclude that only one major PFGE genotype of MRSA clone is
      circulating among the three major regional hospitals in Trinidad and Tobago
      suggesting one of three possible scenarios of microevolution: (1) all were from
      the dissemination of a single epidemic MRSA clone prevailing in these hospitals
      in Trinidad and Tobago; or (2) MRSA in Trinidad and Tobago is evolving more
      slowly than in other countries; or (3) that if other MRSA clones have been
      present in Trinidad and Tobago, they have not persisted.

PMID- 17537662
TI  - Brucellar mastitis: presentation of a case and review of the literature.

PMID- 17537663
TI  - Pilus-mediated epithelial cell death in response to infection with Burkholderia
      cenocepacia.
AB  - Burkholderia cenocepacia is an opportunistic pathogen that can cause serious
      infections in cystic fibrosis (CF) patients. The ET12 lineage appears
      particularly virulent in CF; however, its pathogenesis is poorly understood and
      may be associated with host response. To help characterize this response, the
      ability of B. cenocepacia to induce cytotoxicity and apoptosis in an epithelial
      cell model was examined. Upon infection with B. cenocepacia strain K56-2, A549
      human lung epithelial cells underwent significant cell death; propidium iodine
      staining and DNA fragmentation assays suggested apoptosis. Initiation of cell
      death was independent of the type III secretion system, biofilm formation, and
      secreted bacterial cytotoxins. However, the frequency of cell death was lower in
      cells infected with a non-piliated mutant, K56-2 cblA::Tp. Furthermore, purified
      cbl pili were found to directly induce cytotoxicity in A549 cells and activate
      caspase-9, -8, -7, and -3, the major cysteine proteinases involved in apoptosis.
      It appears that B. cenocepacia cbl pili, which are a distinctive feature of the
      ET12 lineage, act as an initiator of cytotoxicity and apoptosis. Understanding
      the role of cbl pili in the pathogenesis of B. cenocepacia infections offers the
      potential for decreasing the virulence of these potentially life-threatening
      organisms in CF patients.

PMID- 17537664
TI  - Prevention of changes in airway function facilitates Strongyloides venezuelensis
      infection in rats.
AB  - Alterations in lung function and pulmonary symptoms have been described in
      patients infected with helminths with a lung cycle. We have previously shown that
      infection with the nematode Strongyloides venezuelensis induced a significant
      increase in airway hyperreactivity in infected rats. The aim of the present study
      was to test the hypothesis that bronchodilation during the lung phase of parasite
      migration would favor completion of the life cycle and infection indices. For
      this purpose, S. venezuelensis infected rats were treated with salbutamol during
      the first 48 h after the nematode infection. At the dose used (0.25 mg/mL for 10
      min every 4 h), treatment with salbutamol prevented changes in lung function
      during the parasite migration. This was accompanied by a significant increase in
      parasite burden, as assessed in the lung and the small intestine. Parasite
      infected and salbutamol-treated animals also showed a significant increase in
      concentration of IL-10 and IL-4 in homogenates of lungs during the worm migration
      that was followed by stronger lung eosinophilic inflammation at 5 dpi, after the
      larvae had left the host lung. Our data indicates that airway hyperactivity
      reduce parasite progression through the lung, facilitating the action of innate
      or adaptive immune mechanisms.

PMID- 17537665
TI  - A murine model of infection with Rickettsia prowazekii: implications for
      pathogenesis of epidemic typhus.
AB  - Epidemic typhus remains a major disease threat, furthermore, its etiologic agent,
      Rickettsia prowazekii, is classified as a bioterrorism agent. We describe here a
      murine model of epidemic typhus that reproduced some features of the human
      disease. When BALB/c mice were inoculated intravenously with R. prowazekii
      (Breinl strain), they survived but did not clear R. prowazekii infection.
      Immunohistological analysis of tissues and quantitative PCR showed that R.
      prowazekii was present in blood, liver, lungs and brain 1 day after infection and
      persisted for at least 9 days. Importantly, infected mice developed interstitial
      pneumonia, with consolidation of the alveoli, hemorrhages in lungs, multifocal
      granulomas in liver, and hemorrhages in brain, as seen in humans. Circulating
      antibodies directed against R. prowazekii were detected at day 4 post-infection
      and steadily increased for up to 21 days, demonstrating that R. prowazekii
      lesions were independent of humoral immune response. R. prowazekii-induced
      lesions were associated with inflammatory response, as demonstrated by elevated
      levels of inflammatory cytokines including interferon-gamma, tumor necrosis
      factor and the CC chemokine RANTES in the lesions. We concluded that the BALB/c
      mouse strain provides a useful model for studying the pathogenic mechanisms of
      epidemic typhus and its control by the immune system.

PMID- 17537666
TI  - MyD88-dependent activation of dendritic cells and CD4(+) T lymphocytes mediates
      symptoms, but is not required for the immunological control of parasites during
      rodent malaria.
AB  - We investigated the role of different TLRs and MyD88 in host resistance to
      infection and malaria pathogenesis. TLR2(-/-), TLR4(-/-), TLR6(-/-), TLR9(-/-) or
      CD14(-/-) mice showed no change in phenotypes (parasitemia, body weight and
      temperature) when infected with Plasmodium chabaudi chabaudi (AS). MyD88(-/-)
      mice displayed comparable ability to wild type animals in controlling and
      clearing parasitemia. Importantly, MyD88(-/-) mice exhibited impaired production
      of TNF-alpha and IFN-gamma as well as attenuated symptoms, as indicated by
      changes in body weight and temperature during parasitemia. Consistently, CD11b(+)
      monocytes and CD11c(+) dendritic cells from infected MyD88(-/-) mice were shown
      impaired for production of pro-inflammatory cytokines, and in initiating CD4(+) T
      cell responses. Importantly, the inhibition of T cell activation with anti
      CD134L, mostly inhibited IFN-gamma, partially inhibited TNF-alpha production, and
      protected the animals from malaria symptoms. Our findings suggest that MyD88 and
      possibly its associated TLRs expressed by dendritic cells play an important role
      in pro-inflammatory responses, T cell activation, and pathogenesis of malaria,
      but are not critical for the immunological control of the erythrocytic stage of
      P. chabaudi.

PMID- 17537667
TI  - Vascular endothelial growth factor: biology and therapeutic applications.
AB  - While the development of anti-angiogenic therapy, as it pertains to cancer
      treatment, may still be in its infancy relative to well-established modalities
      such as chemotherapy, radiation, and surgery, major strides made in the past
      several decades have allowed translation of basic science discoveries in this
      field into clinical reality. The discovery of key molecular modulators of
      angiogenesis, notably vascular endothelial growth factor (VEGF), has catalyzed
      the development of numerous neutralizing therapeutic agents. The validity of VEGF
      inhibition as a therapeutic strategy has been well supported in randomized
      clinical trials, as well as U.S. Food and Drug Administration approval of the
      VEGF antagonists bevacizumab, sunitinib malate, sorafenib, pegaptinib and
      ranibizumab. Accordingly, this review will (1) briefly review the basic molecular
      biology of VEGF and (2) summarize recent progress in targeting the VEGF molecular
      pathway as therapy for angiogenic diseases such as cancer and age-related macular
      degeneration.

PMID- 17537668
TI  - The discovery of basic fibroblast growth factor/fibroblast growth factor-2 and
      its role in haematological malignancies.
AB  - Basic fibroblast growth factor/fibroblast growth factor-2 is one of the best
      characterized of the pro-angiogenic cytokines. This review describes its history,
      as well as its role in tumor angiogenesis associated with haematological
      malignancies, as traced by the main contributions to the international medical
      literature.

PMID- 17537669
TI  - Wolbachia-host interactions: connecting phenotype to genotype.
AB  - The long-established view of Wolbachia as reproductive parasites of insects is
      becoming complicated as an increasing number of papers describe a richer picture
      of Wolbachia-mediated phenotypes in insects. The search for the molecular basis
      for this phenotypic variability has been greatly aided by the recent sequencing
      of several Wolbachia genomes. These studies have revealed putative genes and
      pathways that are likely to be involved in the host-symbiont interaction. Whereas
      significant progress is being made from comparative genomic studies together with
      the use of model host systems like Drosophila, the ultimate linking of phenotype
      to genotype will require the development of genetic manipulation technology for
      both host and symbiont.

PMID- 17537670
TI  - The antimutagenic activity of the major flavonoids of rooibos (Aspalathus
      linearis): some dose-response effects on mutagen activation-flavonoid
      interactions.
AB  - The antimutagenic properties of the most prevalent flavonoids in rooibos
      (Aspalathus linearis) were compared in the Salmonella typhimurium mutagenicity
      assay using tester strains TA98 and TA100 with, respectively, 2-acetamido
      fluorene (2-AAF) and aflatoxin B(1) (AFB(1)) as mutagens in the presence of
      metabolic activation. The flavonoids included the dihydrochalcones aspalathin and
      nothofagin and their flavone analogues, orientin and isoorientin, and vitexin and
      isovitexin, respectively, as well as luteolin, chrysoeriol, (+)-catechin,
      quercetin, isoquercitrin, hyperoside and rutin. Flavonoid-mutagen interactions
      ranged from antimutagenic, comutagenic and promutagenic to mutagenic, while dose
      response effects were mutagen-specific and ranged from typical to atypical
      including biphasic and threshold effects. Aspalathin and nothofagin and their
      structural flavonoid analogues displayed moderate antimutagenic properties while
      luteolin and to some extent, chrysoeriol, showed activities comparable to those
      of the green tea flavonoid (-) epigallocatechin gallate (EGCG). Apart from their
      mutagenic and promutagenic properties, quercetin and isoquercitrin exhibited
      concentration-dependent comutagenic and/or antimutagenic effects against 2-AAF-
      and AFB(1)-induced mutagenesis. Different structural parameters known to affect
      the antimutagenic properties of flavonoids include their hydrophilic or
      lipophilic nature due to the extent of hydroxylation and O-methylation,
      glycosylation on the A and B rings, the C4-keto group and the C2-C3 double bond.
      The C ring does not appear to be a prerequisite when comparing for the
      antimutagenic activity of the dihydrochalcones when compared of the
      dihydrochalcones with the structural flavone analogues.

PMID- 17537671
TI  - Molecular screening shows extensive HIV-1 genetic diversity in Central West
      Brazil.
AB  - BACKGROUND: Information is limited about HIV-1 subtypes circulating in less
      populated Brazilian areas where the AIDS epidemic is expanding, such as in the
      Central West region. OBJECTIVE: To describe HIV-1 subtypes in patients from the
      States of Goias, Mato Grosso do Sul and Mato Grosso in Central West Brazil. STUDY
      DESIGN: Heteroduplex mobility analysis of nested-PCR products from env (primers:
      ED5/ED12, ES7/ES8) and gag regions (primers: H1P202/H1G777, H1Gag1584/g17) of 406
      HIV-1 isolates from Goias (n=271), Mato Grosso do Sul (n=85) and Mato Grosso
      (n=50) collected from 2001 to 2004. RESULTS: Median age of patients was 26 years
      (1-79 range), 68.7% (279/406) females, 69.9% (269/385) sexual exposure, 14.3%
      parenteral risk, 15.8% vertical cases. Overall 69.9% (284/406) of HIV-1 subtypes
      were concordant B(env)/B(gag), 1.7% F(env)/F(gag) and 1% C(env)/C(gag).
      Discordant HIV-1 isolates were 14.5% (59/406), mainly B(env)/F(gag) and
      F(env)/B(gag) (49/59); five were B(env)/D(gag), four B(env)/C(gag) and one
      C(env)/D(gag). B/B and discordant B/F isolates were detected among all risk
      categories and among children and adults. CONCLUSION: Extensive genetic diversity
      of HIV-1 was observed in Central West Brazil. Continued molecular studies should
      monitor the changing dynamics of HIV-1 over time especially in areas where the
      epidemic is growing.

PMID- 17537672
TI  - The circadian perspective in medicine.

PMID- 17537673
TI  - How pattern recognition receptor triggering influences T cell responses: a new
      look into the system.
AB  - Signaling through pattern recognition receptors (PRRs) in antigen-presenting
      cells (APCs) is required for the induction of T cell responses. PRR triggering in
      APCs induces important cellular modifications that have profound effects on
      antigen internalization, processing, MHC loading and antigen presentation.
      Accumulating experimental evidence also suggests that the fate of T cell
      responses depends strongly on the type of PRR triggered and the timing of PRR
      signaling. Here, we discuss the beneficial effects of PRR stimulation in the
      context of priming naive T cells, the generation and maintenance of
      effector/memory T cells, and the induction or break of tolerance. We propose a
      new classification into opsonic, phagocytic and instructive PRRs based on the
      functional properties of the receptors.

PMID- 17537674
TI  - The case for maternal vaccination against pertussis.
AB  - Despite high vaccine coverage, the incidence of pertussis is increasing in a
      number of countries. Particularly alarming is the increase of pertussis in
      infants too young to be (fully) vaccinated, because the highest morbidity and
      mortality is observed in this category. Maternal vaccination offers the
      possibility to protect infants from birth until immunity is induced by active
      vaccination, and has been shown to be effective and safe for tetanus over long
      periods of time. Maternal vaccination studies with whole-cell pertussis vaccines
      have not shown serious adverse effects in mother and child. In one study,
      protection of newborn babies was found. Additional support for the efficacy of
      maternal vaccination comes from studies showing that transfer of antibodies
      confers protection against pertussis. Maternal vaccination might be an effective
      way to decrease morbidity and mortality caused by pertussis in newborn babies.

PMID- 17537675
TI  - Testing the limits of case finding for HIV prevention.
AB  - HIV testing technologies have been available for two decades, but concerns about
      stigma and discrimination have historically tempered the application of case
      finding-a cornerstone of public-health practice-to combat the HIV/AIDS pandemic.
      The recent expansion of access to HIV treatment has resulted in a shift of
      emphasis from pairing testing with rigorous risk-reduction prevention
      counselling, to applying testing to find infected individuals, address their care
      and treatment needs, and prevent them from infecting others. However, the
      efficacy of case finding for infectious disease prevention is contingent on two
      basic principles: the ability to identify infected individuals before further
      transmission occurs, and the availability of effective strategies to prevent such
      transmission from taking place. Although there is evidence that specific
      approaches to HIV counselling and testing can support behaviour change, both high
      infectivity during early HIV infection and specific sexual network structures
      could combine to substantially limit our ability to identify cases before ongoing
      transmission occurs. Facilitating the broader adoption of prevention behaviours
      therefore remains essential to prevent the continued spread of HIV.

PMID- 17537676
TI  - A clinical prognostic scoring system for Guillain-Barre syndrome.
AB  - BACKGROUND: Guillain-Barre syndrome (GBS) is an acute post-infectious immune
      mediated peripheral neuropathy with a highly variable clinical course and
      outcome. We aimed to develop and validate a scoring system based on clinical
      characteristics in the acute phase of GBS to predict outcome at 6 months.
      METHODS: We studied patients with GBS who were unable to walk independently. A
      derivation set included 388 patients from two randomised controlled trials and
      one pilot study. Potential predictors were assessed for their association with
      the inability to walk independently at 6 months. A simple clinical scoring system
      was developed on the basis of regression coefficients of predictors in a
      multivariable logistic regression model. Model performance was quantified with
      respect to discrimination (area under receiver operating characteristics curve,
      AUC) and calibration (graphically). We validated our scoring system in a set of
      374 patients from another randomised trial. FINDINGS: We included three variables
      that were predictive of poor outcome at 6 months in our model: age, preceding
      diarrhoea, and GBS disability score at 2 weeks after entry. Scores ranged from 1
      to 7, with three categories for age, two for diarrhoea, and five for GBS
      disability score at 2 weeks. Predictions corresponding to these prognostic scores
      ranged from 1% to 83% for the inability to walk independently at 6 months.
      Predictions agreed well with observed outcome frequencies (adequate calibration)
      and showed a very good discriminative ability (AUC 0.85) in both data sets.
      INTERPRETATION: A simple scoring system for patients with GBS, based on three
      clinical characteristics, accurately predicts outcome at 6 months. The system
      could be used to counsel individual patients and identify high-risk groups to
      guide future trials.

PMID- 17537677
TI  - Inflammation and bone erosion are suppressed in models of rheumatoid arthritis
      following treatment with a novel Syk inhibitor.
AB  - Spleen tyrosine kinase (Syk), a key mediator of immunoreceptor signaling in
      inflammatory cells, is essential for immune complex-mediated signal transduction
      initiated by activated receptors for immunoglobulin G. In collagen-induced
      arthritis, R788/R406, a novel and potent small molecule Syk inhibitor suppressed
      clinical arthritis, bone erosions, pannus formation, and synovitis. Serum anti
      collagen type II antibody levels were unaltered, while the half-life of exogenous
      antibody was extended when co-administered with R406. Expression of the targeted
      kinase (Syk) in synovial tissue correlated with the joint level of inflammatory
      cell infiltrates and was virtually undetectable in treated rats. Syk inhibition
      suppressed synovial cytokines and cartilage oligomeric matrix protein (COMP) in
      serum, suggesting a sensitive and reliable biomarker for R406 activity. These
      results highlight the role of activating Fcgamma receptors in inflammatory
      synovitis and suggest that interruption of the signaling cascade with a novel Syk
      inhibitor may be a useful addition to immunosuppressive disease-modifying anti
      rheumatic drugs currently used in the treatment of human autoimmune diseases such
      as rheumatoid arthritis.

PMID- 17537678
TI  - Current approaches to the use of generic antiepileptic drugs.
AB  - Generic substitution is encouraged as a cost containment strategy for the
      management of health care resources. However, in epilepsy, the consequences of
      loss of symptom control are important, and antiepileptic drugs have narrow
      therapeutic indices. For this reason, generic substitution may be problematic,
      and certain health authorities have excluded antiepileptic drugs from overall
      policy recommendations on generic prescribing. The absence of bioequivalence data
      among generic forms and the relatively broad criteria for bioequivalence with the
      branded drug allow differences in drug exposure to arise that may be clinically
      relevant and necessitate monitoring of plasma levels when switching formulations
      to avoid loss of seizure control or emergence of side effects. Management of
      these issues carries a significant cost, which should be weighed carefully
      against the cost savings acquired when purchasing the drug. Both physicians and
      patients have a right to be informed and approve before pharmacists make a
      generic substitution or switch between generics.

PMID- 17537679
TI  - Relationship between optimism, disease variables, and health perception and
      quality of life in individuals with epilepsy.
AB  - Epilepsy is a relatively frequent chronic condition with an important impact on
      the health perception and quality of life (QOL) of patients. The aim of the
      present study was to identify variables related to health status perception and
      QOL in persons with epilepsy. Participants were 200 persons with epilepsy, 53.5%
      of whom were males. The mean age was 39.6; 95% had seizures, and 99% were taking
      antiepileptic medication. The self-report questionnaire administered assessed
      four types of variables: demographic, disease, epilepsy-specific optimistic
      attitude, and outcome variables. Results demonstrated that an optimistic
      orientation is related to better perception of physical and mental health status
      and better perception of QOL. The variables that best predict positive outcomes
      are optimistic orientation, perception of cognitive functioning, and perception
      of seizure control. These results question the importance attributed to seizure
      characteristics for everyday functioning and everyday life of individuals with
      epilepsy, and stress the importance of facilitating an epilepsy-specific
      optimistic orientation.

PMID- 17537680
TI  - Membrane and synaptic properties of nucleus tractus solitarius neurons projecting
      to the caudal ventrolateral medulla.
AB  - Projections from the nucleus of tractus solitarius (NTS) to the caudal
      ventrolateral medulla (CVLM) are important in mediating autonomic reflexes.
      However, little is known about the cellular properties of the CVLM-projecting NTS
      neurons. In this study, the CVLM-projecting NTS neurons were retrogradely labeled
      by fluorescent microspheres injected into the CVLM. Whole cell voltage- and
      current-clamp recordings were performed on labeled NTS neurons in coronal
      brainstem slices. Compared with unlabeled neurons, the labeled NTS neurons had
      more depolarized resting membrane potentials, larger input resistance, and higher
      firing activity in response to depolarizing currents. Bath application of an
      ionotropic glutamate receptor antagonist kynurenic acid and a non-NMDA receptor
      antagonist CNQX significantly decreased the firing activity in the majority of
      labeled NTS neurons. In contrast, an NMDA receptor antagonist AP5 failed to alter
      the firing activity in labeled neurons tested. While the glycine receptor
      antagonist strychnine had no effect on the firing activity, blockade of
      GABA(A)receptors with bicuculline significantly increased the firing rate in the
      majority of labeled NTS neurons. Furthermore, CNQX blocked the majority of
      spontaneous excitatory postsynaptic currents (EPSCs) and evoked EPSCs elicited by
      stimulation of the tractus solitarius. The residual spontaneous and evoked EPSCs
      were abolished by the nicotinic receptor antagonist mecamylamine and the
      purinergic P2X receptor antagonist iso-PPADS. Finally, while bicuculline
      completely blocked the miniature inhibitory postsynaptic currents (IPSCs), the
      spontaneous and evoked IPSCs were abolished by a combination of bicuculline and
      strychnine in labeled NTS neurons. Collectively, these data suggest that the CVLM
      projecting neurons are a population of neurons with distinctive membrane
      properties.

PMID- 17537682
TI  - Three phase liquid phase microextraction of phenylacetic acid and phenylpropionic
      acid from biological fluids.
AB  - Three phase liquid phase microextraction (three phase LPME) technique coupled
      with HPLC-UV has been applied as a sensitive and efficient sample preparation
      method to determine phenylacetic acid (PAA) as a biomarker of depressive
      disorders and phenylpropionic acid (PPA) in biological fluids. The compounds were
      extracted from 3.0 ml aqueous solution with the adjustment of pH at a fixed value
      in the range of 2.0-3.5 (donor solution) into an organic phase (1-hexanol)
      layered on the surface of the donor solution and finally back-extracted into 4.0
      microl of the acceptor microdrop (pH 11.1) located at the end of the microsyringe
      needle. After a prescribed back-extraction time, the acceptor microdrop was
      withdrawn into the microsyringe and then directly injected into the HPLC system.
      In order to achieve maximum extraction efficiency, different parameters affecting
      the extraction conditions were optimized. At the optimum conditions (donor
      solution: 2.3M Na(2)SO(4), pH 2.0-3.5; organic membrane: 95 microl of 1-hexanol;
      acceptor solution: 4.0 microl of 0.1M NH(3)/NH(4)(+) with pH 11.1; donor solution
      temperature: 45-50 degrees C; extraction time: 20 min and back-extraction time:
      12 min), up to 110-fold enrichment factor was obtained. The calibration curve for
      these analytes was linear in the range of 1-5000 microg/l with r(2)>0.998. The
      intraday and interday RSD% were below 6.5% and the limits of detection (LODs) for
      both analytes were 0.2 microg/l (based on S/N=3). The proposed technique is a low
      cost, simple and sensitive method with highly clean-up effect. Finally, this
      technique was successfully utilized for the detection of target analytes in human
      urine, serum and plasma.

PMID- 17537683
TI  - Development and validation of a liquid chromatography-tandem mass spectrometry
      assay for determination of raloxifene and its metabolites in human plasma.
AB  - This paper describes the development and validation of a method for the detection
      of raloxifene (Ral) and its two glucuronide metabolites, raloxifene-6-glucuronide
      (M1) and raloxifene-4'-glucuronide (M2), in human plasma samples. Both
      glucuronides were synthesized enzymatically, purified and used as authentic
      standards. The assay involves a simple solid phase extraction (SPE) procedure of
      0.5 mL of human plasma and subsequent analysis by LC-MS-MS. The recoveries were
      higher than 71% and chromatographic separation of all the analytes was
      accomplished in less than 7 min. Linear ranges (r(2)>0.99) were found from 0.200
      to 340 microg/L, from 1.600 to 2720 microg/L and from 0.088 to 60.00 microg/L,
      for M1, M2 and Ral, respectively. The limits of detection achieved were 8, 11 and
      6 ng/L for M1, M2 and Ral, respectively. The method presented was successfully
      applied to a genetic polymorphism study of 47 plasma samples from women taking
      Evista (raloxifene hydrochloride).

PMID- 17537681
TI  - Innervation of the gastrointestinal tract: patterns of aging.
AB  - The gastrointestinal (GI) tract is innervated by intrinsic enteric neurons and by
      extrinsic projections, including sympathetic and parasympathetic efferents as
      well as visceral afferents, all of which are compromised by age to different
      degrees. In the present review, we summarize and illustrate key structural
      changes in the aging innervation of the gut, and suggest a provisional list of
      the general patterns of aging of the GI innervation. For example, age-related
      neuronal losses occur in both the myenteric plexus and submucosal plexus of the
      intestines. These losses start in adulthood, increase over the rest of the life
      span, and are specific to cholinergic neurons. Parallel losses of enteric glia
      also occur. The extent of neuronal and glial loss varies along an oral-to-anal
      gradient, with the more distal GI tract being more severely affected.
      Additionally, with aging, dystrophic axonal swellings and markedly dilated
      varicosities progressively accumulate in the sympathetic, vagal, dorsal root, and
      enteric nitrergic innervation of the gut. These dramatic and consistent patterns
      of neuropathy that characterize the aging autonomic nervous system of the GI
      tract are candidate mechanisms for some of the age-related declines in function
      evidenced in the elderly.

PMID- 17537684
TI  - Quantitative HPLC-UV method for the determination of firocoxib from horse and dog
      plasma.
AB  - A sensitive reversed-phase HPLC-UV method was developed for the determination of
      firocoxib, a novel and highly selective COX-2 inhibitor, in plasma. A 1.0 mL dog
      or horse plasma sample is mixed with water and passed through a hydrophobic
      lipophilic copolymer solid-phase extraction column to isolate firocoxib.
      Quantitation is based on an external standard curve. The method has a validated
      limit of quantitation of 25 ng/mL and a limit of detection of 10 ng/mL. The
      validated upper limit of quantitation was 2500 ng/mL for horses and 10,000 ng/mL
      for dogs. The average recoveries ranged from 88-93% for horse plasma and 96-103%
      for dog plasma. The coefficient of variation in all cases was less than 10%. This
      method is suitable for the analysis of clinical samples from pharmacokinetic and
      bioequivalence studies and drug monitoring.

PMID- 17537685
TI  - Purification of recombinant phenylalanine dehydrogenase by partitioning in
      aqueous two-phase systems.
AB  - This study presents the partitioning and purification of recombinant Bacillus
      badius phenylalanine dehydrogenase (PheDH) in aqueous two-phase systems (ATPS)
      composed of polyethylene glycol 6000 (PEG-6000) and ammonium sulfate. A single
      step operation of ATPS was developed for extraction and purification of
      recombinant PheDH from E. coli BL21 (DE3). The influence of system parameters
      including; PEG molecular weight and concentration, pH, (NH(4))(2)SO(4)
      concentration and NaCl salt addition on enzyme partitioning were investigated.
      The best optimal system for the partitioning and purification of PheDH was 8.5%
      (w/w) PEG-6000, 17.5% (w/w) (NH(4))(2)SO(4) and 13% (w/w) NaCl at pH 8.0. The
      partition coefficient, recovery, yield, purification factor and specific activity
      values were of 92.57, 141%, 95.85%, 474.3 and 10424.97 U/mg, respectively. Also
      the K(m) values for L-phenylalanine and NAD(+) in oxidative deamination were
      0.020 and 0.13 mM, respectively. Our data suggested that this ATPS could be an
      economical and attractive technology for large-scale purification of recombinant
      PheDH.

PMID- 17537686
TI  - Determination of palmatine in canine plasma by liquid chromatography-tandem mass
      spectrometry with solid-phase extraction.
AB  - A sensitive and specific high-performance liquid chromatography-tandem mass
      spectrometry (HPLC-MS-MS) method has been developed and validated for the
      determination of palmatine in canine plasma. Palmatine and jatrorrhizine
      (internal standard, I.S.) were extracted from plasma samples by solid-phase
      extraction (SPE) using Oasis HLB cartridges. The chromatographic separation was
      performed on a Waters XTerra MS C(18) reversed-phase column at 30 degrees C. The
      gradient mobile phase, delivered at 0.25 mL/min, was composed of a mixture of
      acetonitrile -0.1% (v/v) acetic acid aqueous solution adjusted to pH 2.8 with
      triethylamine. Positive electrospray ionization was utilized as the ionization
      source. Palmatine and the internal standard (I.S.) were determined using multiple
      reaction monitoring (MRM) of precursor-->product ion transitions at m/z 352-->336
      and m/z 338-->322, respectively. The lower limit of quantification (LLOQ) was 0.1
      ng/mL using 100 microL plasma samples and the linear calibration range was from
      0.1 to 500 ng/mL. The inter-day and intra-day RSDs were lower than 9.9% and the
      recoveries of palmatine ranged from 87.3 to 100.9%. The mean extraction
      recoveries of palmatine and the I.S. were 99.2 and 96.8%, respectively. The
      method has been successfully applied to the pharmacokinetic studies of palmatine
      in beagle dogs after oral administration and intramuscular injection of
      palmatine.

PMID- 17537687
TI  - Isolation, characterization and chemobiological quantification of alpha
      glucosidase enzyme inhibitory and free radical scavenging constituents from
      Derris scandens Benth.
AB  - The hexane and chloroform extracts of Derris scandens have displayed potent alpha
      glucosidase inhibitory and moderate free radical scavenging activities.
      Phytochemical investigation of the active extracts led to the isolation of three
      new prenylated isoflavones, isoscandinone, scandenin A and scandenin B in
      addition to scandenone, scandinone and 4', 5', 7-trihydroxybiprenylisoflavone as
      the main constituents, having alpha-glucosidase enzyme inhibitory and free
      radical scavenging properties. A reversed-phase HPLC method is developed to
      quantify these active principles in the plant material, which can serve as an
      effective quality control method for standardization of D. scandens.

PMID- 17537688
TI  - Sample preparation and bioinformatics in MALDI profiling of urinary proteins.
AB  - One of the challenges of current proteomics research is identifying healthy and
      diseased mass spectrometric (MS) patterns within biological fluids. As a result,
      sample preparation methodologies, as well as the mathematical tools utilized for
      MS data analysis become pivotal. This study involves a thorough evaluation of the
      reproducibility and protein resolution that various urinary protein preparation
      methodologies provide in MALDI MS analysis. Several precipitation approaches,
      ultrafiltration, as well as direct dilution of urine in MALDI MS compatible
      buffers were applied in combination to a thorough bioinformatics analysis of the
      generated MS data. Our results indicate that ultrafiltration, as well as direct
      dilution of urine in TFA, can provide information rich and reproducible spectra
      for mass ranges up to 20 kDa. The importance of the presence of peak
      reproducibility filters when generating disease classification models is
      suggested.

PMID- 17537689
TI  - Transient precursor strategy or very small biological apatite crystals?
AB  - The mechanisms of skeletal mineralization have been studied and debated for
      decades. Recent Raman spectroscopic identification of octacalcium phosphate-like
      phosphate ions and possibly amorphous calcium phosphate ions in nascent bone
      mineral were claimed to support a transient precursor strategy for bone apatite
      formation. However, this data does not refute the theory that the newest,
      detectable bone mineral is very small, poorly crystalline biological apatite,
      because non-apatitic phosphate species have previously been identified in
      biological apatite and detected on the surfaces of nano-sized hydroxyapatite
      crystals.

PMID- 17537692
TI  - "Bound in a nutshell": thoughts on complexity, reductionism, and "infinite
      space".
AB  - Pluralism is the hallmark of 21st century psychoanalytic discourse. Nevertheless,
      an unpleasant byproduct of pluralism is a tendency in some quarters to retreat
      into orthodoxy, stemming from a perceived need to shore up theoretical boundaries
      in the service of differentiating one theory from another. The delineation of
      borders places us at a risk of losing sight of the fact that genuine
      psychoanalytic thinking is fundamentally non-reductionistic. Moreover, the core
      psychoanalytic notion of overdetermination, which Freud never abandoned
      throughout his career, has recently been neglected as authors argue in their
      communications that one point of view is better than another. Both analysts and
      their patients secretly are drawn to simple formulations that eschew complexity.
      The need to remain open to the "infinite space" of meaning, motive, and causation
      should be a hallmark of clinical psychoanalytic practice. The author considers
      the implications for technique, and provides case material to illustrate some of
      the challenges inherent in approaching psychoanalytic work as a complex
      phenomenon.

PMID- 17537693
TI  - On talking-as-dreaming.
AB  - Many patients are unable to engage in waking-dreaming in the analytic setting in
      the form of free association or in any other form. The author has found that
      "talking-as-dreaming" has served as a form of waking-dreaming in which such
      patients have been able to begin to dream formerly undreamable experience. Such
      talking is a loosely structured form of conversation between patient and analyst
      that is often marked by primary process thinking and apparent non sequiturs.
      Talking-as-dreaming superficially appears to be "unanalytic" in that it may seem
      to consist "merely" of talking about such topics as books, films, etymology,
      baseball, the taste of chocolate, the structure of light, and so on. When an
      analysis is "a going concern," talking-as-dreaming moves unobtrusively into and
      out of talking about dreaming. The author provides two detailed clinical examples
      of analytic work with patients who had very little capacity to dream in the
      analytic setting. In the first clinical example, talking-as-dreaming served as a
      form of thinking and relating in which the patient was able for the first time to
      dream her own (and, in a sense, her father's) formerly unthinkable, undreamable
      experience. The second clinical example involves the use of talking-as-dreaming
      as an emotional experience in which the formerly "invisible" patient was able to
      begin to dream himself into existence. The analyst, while engaging with a patient
      in talking-as-dreaming, must remain keenly aware that it is critical that the
      difference in roles of patient and analyst be a continuously felt presence; that
      the therapeutic goals of analysis be firmly held in mind; and that the patient be
      given the opportunity to dream himself into existence (as opposed to being dreamt
      up by the analyst).

PMID- 17537694
TI  - Creativity and dialectical phenomena: from dialectical edge to dialectical space.
AB  - The seeds of creativity have the potential to germinate and flourish within the
      rich, ambiguous and unsettling tapestry of the core dialectical tensions related
      to the central organizing dialectic, life and death, generated in the patient
      analyst relating. The author introduces the concept of the "dialectical edge" and
      describes it as the pivotal point in the dialectical struggle within these core
      dialectical dilemmas. This is a fluid, emotionally evocative threshold, where
      there is maximum potential for change, as well as for homeostatic stagnation.
      Drawing on Winnicott, the author illustrates how the presence of an edge within
      these dialectical dilemmas has the potential to open up into a creative,
      reflective space. He suggests that this, however, will depend on the therapist's
      capacity to contain/hold at this edge the arousing and intense affects--such as
      anxiety, dread, excitement and passion--that are inevitably generated at these
      pivotal relational moments. This will determine whether the patient will move
      forwards into the light of a creative, reflective, dialectical space, or
      backwards into collapsed, non-reflective darkness, where fluid oscillation is
      transformed into rigid ossification. The author uses a clinical example to
      illustrate these dialectical phenomena, with a special focus on two clinically
      relevant dialectics, i.e. "ritual versus spontaneity" and "closeness versus
      separateness".

PMID- 17537695
TI  - The illumination of history.
AB  - Formulations regarding the patient's history have not only played an important
      part in understanding the patient, but interpretations explicitly linking the
      present with the past have been seen as central to the therapeutic process. In
      this paper the author considers the role of historical reconstruction in bringing
      about psychic change. He emphasizes the therapeutic value that lies in the
      exploration of the way the patient's history is embodied in his internal object
      relationships, becoming manifested in the transference-countertransference
      relationship. The author presents clinical material which he suggests allowed the
      analyst to follow the way the patient's internal object relations, coloured by
      her history, became expressed and played out in the sessions. He suggests that,
      when these processes can be followed and addressed in the present, this may lead
      to a diminution in the underlying anxieties. This can thus promote psychic change
      by freeing the patient's capacity to achieve a sense of connection with her
      history, and to tolerate the meaning of what emerges, which illuminates both the
      present and the past.

PMID- 17537696
TI  - The impact of intrusive identification in the analytic process: some implications
      of real trauma and phantasy.
AB  - In this paper, the author aims to show a possible understanding of very primitive
      identifications, especially intrusive identifications, when associated with
      traumatic situations and expressed through current phantasies related to these
      experiences. At first glance, this understanding could be considered quite
      straightforward. However, the original contribution offered by the author is the
      participation of this special kind of combination in the formation of the
      primitive intrusive identifications and its association with the imprisonment
      inside the primitive object of identification, especially the mother. The author
      proposes the amplification of the clinical use of the concept of "life in the
      claustrum", originally described by Meltzer, moving beyond persecutory
      claustrophobic situations. He illustrates the phenomenon with the analytic work
      carried out with a patient whose narcissistic and intrusive character was
      structured on the basis of primitive intrusive identifications and phantasies
      related to the claustrum inside the mother. The patient's imprisonment inside the
      maternal compartments has, as its background, the phantasies related to the
      infantile traumatic experience of the death of the patient's brother, which are
      reproduced in the analytic relationship.

PMID- 17537697
TI  - Lacan.
AB  - Jacques Lacan belonged to the second generation of French psychoanalysts which,
      thanks to the arrival in France of Rudolf Loewenstein, was the first to benefit
      from a training analysis of sufficient quality and duration. Lacan left the
      Societe Psychanalytique de Paris and the International Psychoanalytic Association
      in 1953, following a controversy over the short sessions he gave his patients.
      For Lacan, the anxiety of being absorbed by the object is the principal anxiety
      from which the anxieties of separation, castration or fragmentation are derived,
      which may explain why he did not keep his patients for a sufficient length of
      time. Lacan transformed his difficulty into an advocated technique, which he
      justified by making a critique of the classical technique. He founded his own
      international psychoanalytic association, in which selection only occurs when the
      analyst is already at a very advanced stage in his career ("the authorization of
      an analyst can only come from himself"). We are indebted to Lacan for having
      drawn the attention of analysts to the role of language, and especially of words
      with a double meaning, in the genesis of interpretation, but his theory of
      language, founded on the assimilation of psychoanalysis to structural linguistics
      and anthropology, has collapsed. Many of Lacan's other theoretical contributions,
      such as the renewed interest in the apres-coup, the place of mirror relations in
      narcissism, the distinction between what he calls jouissance and the orgasm, or
      between the "real" and reality, have been gradually integrated by analysts who
      accept neither his technique nor his laxity in training.

PMID- 17537698
TI  - Can research influence clinical practice?
AB  - After briefly reviewing the unfavourable reception accorded empirical research by
      parts of the psychoanalytic community, as well as some of the benefits to
      clinical practice of analysts being involved in research activities, the author
      examines whether the findings of process and outcome research in psychotherapy
      and psychoanalysis can help identify the most appropriate forms of intervention
      for producing therapeutic change, given the specific condition of the patient and
      the relationship that the individual establishes with the analyst. He argues that
      research findings can influence clinical practice on various levels and in
      different areas, and goes on to examine a number of related issues: the
      specificity of therapeutic interventions versus the relevance of common curative
      factors; the dyadic conception of technique and ways of understanding the
      therapeutic action of the treatment alliance; and the strategic or heuristic
      conception in psychoanalytic therapy. Finally, the author presents clinical
      material with the aim of illustrating how the knowledge acquired through research
      can be applied to psychoanalytic treatment.

PMID- 17537699
TI  - The supervisory field and projective identification.
AB  - Taking as their starting point the Baranger and Baranger model of the
      "psychoanalytic field", the authors extend the notion of intersubjectivity in the
      analytic relationship to the supervision process. They use a practical example of
      a supervision to show the development of what they term the "supervisory field",
      formed from the superimposition of the two fields of analyst-patient and
      supervisor-supervisee. They emphasize the interplay of projective identifications
      with objects emanating from the inner world of the patient that are relived in
      the analytic relationship and transposed to the supervisory field. They believe
      that the concept of the "supervisory field" contributes to a deeper understanding
      of the unconscious processes occurring in the mind of analysand, supervisee and
      supervisor during supervision, particularly regarding the identification,
      comprehension and resolution of persistent disturbances in the supervisory
      process.

PMID- 17537700
TI  - Confidentiality, privacy, and the facilitating role of psychoanalytic
      organizations.
AB  - Burgeoning external threats to confidentiality by claims to clinical information
      create unprecedented challenges for psychoanalysts. Internal threats arise from
      the use of clinical material for educational, scientific and historical purposes.
      Traditionally, confidentiality is considered a patient's right and an analyst's
      obligation; privacy is not usually stated as a professional requirement. Little
      consideration has been given to the impact of the confidentiality and privacy
      dilemmas that analysts encounter throughout their careers. There has been no
      systematic examination of the confidentiality policies of psychoanalytic
      organizations, nor has their role in facilitating maintenance of patient
      confidentiality and analysts' privacy been made explicit. The research reported
      here was undertaken to address these issues and to obtain baseline information
      about the current confidentiality policies and practices of psychoanalytic
      organizations in three English-speaking countries (Britain, Canada and the USA).
      The author discusses survey results in the light of the challenges which arise at
      each phase of the analytic career. She makes suggestions as to how psychoanalytic
      organizations can and should facilitate analysts' resolutions of contemporary
      confidentiality and privacy dilemmas.

PMID- 17537701
TI  - Infant observation: a range of questions and challenges for contemporary
      psychoanalysis.
AB  - The author attempts to integrate several perspectives within the field of infant
      observation that reflect the analyst's personal experience as a clinician, as a
      professor at the analytic institute and as a researcher in the field of
      psychoanalysis. Can infant observation contribute to analytic technique, theory
      and training? If so, what would be the nature of such contribution? To answer
      these questions, the author reviews the literature on infant observation from
      Freud to the present, highlighting Latin American contributions to this subject.
      She makes reference to the role of technological innovations, which have allowed
      videotaping, repeated observations, temporal segmentation and computerized
      programs, thus giving rise to microanalytic research. This discussion prompts the
      question about the contributions made by systematic research to clinical
      practice. To tackle this question, the author presents both a clinical vignette
      taken from her personal experience, and the current debate on this subject as it
      appears in the work of Daniel Stern and Andre Green. Finally, she presents some
      conclusions that are part of an ongoing debate in the psychoanalytic field.

PMID- 17537702
TI  - From Dream story (Schnitzler) to Eyes wide shut (Kubrick): from identity through
      meaning formation to identity through excitation.
AB  - Using different psychoanalytic points of view, in this comparative study of
      "Traumnovelle" by Schnitzler and "Eyes Wide Shut" by Kubrick the author analyses
      the cultural changes between the first and last thirds of the 20th century. This
      change consists in the way "facts of life" are dealt with. It is a change from
      identity through insight and understanding to an identity through excited self
      objectification. This change proceeds along the lines of "I think therefore I am"
      to "I feel therefore I am" arriving at "I am excited, therefore I am noticed and
      thus I am". In the description and illustration of 48 hours in the life of a
      married couple, this transformation from thinking to feeling and sensing is made
      tangible. After 9 years of being married, the couple faces the end of their
      passionate love. They struggle with the primordial anxiety in love life: the
      traumatic loss of faith in one's capacity to love. This transformation is
      accompanied by a change in media that symbolizes the couple's experience: from
      the language of dreaming, reading and listening in Schnitzler to the
      representation in audiovisual media, i.e. visual art, theatre, movies and public
      events in Kubrick. It marks a change in the representation of psychic life in
      space and time.

PMID- 17537703
TI  - The superego, narcissism and Great Expectations.
AB  - The author notes that the concepts of the superego and narcissism were linked at
      conception and that superego pathology may be seen as a determining factor in the
      formation of a narcissistic disorder; thus an examination of the superego can
      function as a "biopsy", indicating the condition of the personality as a whole.
      Charles Dickens's novel "Great Expectations" is presented as a penetrating
      exploration of these themes and it is argued that in Pip, the central character,
      Dickens provides a perceptive study of the history of a narcissistic condition.
      Other key figures in the book are understood as superego representations and, as
      such, integral to the vicissitudes of Pip's development. In particular, the
      lawyer Jaggers is considered as an illustration of Bion's notion of the "ego
      destructive superego". In the course of the paper, the author suggests that Great
      Expectations affirms the psychoanalytic understanding that emotional growth and
      some recovery from narcissistic difficulties necessarily take place alongside
      modification of the superego, allowing for responsible knowledge of the state of
      the object and the possibility of realistic reparation.

PMID- 17537704
TI  - Julie's museum: the evolution of thinking, dreaming and historicization in the
      treatment of traumatized patients.

PMID- 17537705
TI  - Two faces of Thanatos: Broken flowers (2005) and Ai no corrida (1976).
AB  - Since Freud formulated the death instinct concept, it has received widely diverse
      interpretations. Even Freud advanced two versions. The concomitant analyses of
      two films, "Ai no Corrida" (1976) [ In the realm of the senses (1977)] and
      "Broken Flowers" (2005) evince Thanatos's two faces: the cold death of decathexis
      of an object, in the case of Don (in "Broken Flowers" ) and the hot death of the
      subject-object fusion in Sada's case ("Ai no Corrida"). In our analysis, we
      elaborate two possible vicissitudes of the death instinct: in "Broken Flowers" ,
      the main character finds an 'analyst' and is cured. In "Ai no Corrida", the
      protagonist meets a complementary object and goes mad.

PMID- 17537707
TI  - Prevalence of avian influenza and host ecology.
AB  - Waterfowl and shorebirds are common reservoirs of the low pathogenic subtypes of
      avian influenza (LPAI), which are easily transmitted to poultry and become highly
      pathogenic. As the risk of virus transmission depends on the prevalence of LPAI
      in host-reservoir systems, there is an urgent need for understanding how host
      ecology, life history and behaviour can affect virus prevalence in the wild. To
      test for the most important ecological correlates of LPAI virus prevalence at the
      interspecific level, we applied a comparative analysis by using quantitative data
      on 30 bird species. We controlled for similarity among species due to common
      descent, differences in study effort and for covariance among ecological
      variables. We found that LPAI prevalence is a species-specific attribute and is a
      consequence of virus susceptibility, as it was negatively associated with the
      relative size of the bursa of Fabricius, an estimate of juvenile immune function.
      Species that migrate long distances have elevated prevalence of LPAI independent
      of phylogeny and other confounding factors. There was also a positive
      interspecific relationship between the frequency of surface feeding and virus
      prevalence, but this was sensitive to phylogenetic relatedness of species.
      Feeding in marine habitats is apparently associated with lower virus prevalence,
      but the effect of water salinity is likely to be indirect and affected by
      phylogeny. Our results imply that virus transmission via surface waters and
      frequent intra- and interspecific contacts during long migration are the major
      risk factors of avian influenza in the wild. However, the link between
      exploitation of surface waters and LPAI prevalence appears to be weaker than
      previously thought. This is the first interspecific study that provides
      statistical evidence that host ecology, immunity and phylogeny have important
      consequence for virus prevalence.

PMID- 17537708
TI  - Gender differences in the community service use attitudes of older spousal
      caregiver-care recipient couples.
AB  - Prior research has consistently overlooked spousal care recipients' attitudes
      toward service use within the caregiver-care recipient dyadic context. To address
      this gap in knowledge, this exploratory study collected data from both caregiver
      and care recipient spousal informants to compare their community service use
      attitudes by gender. This study employed a purposive sample of 30 older spousal
      caregiver-care recipient couples (N = 60). Service use attitude measures were
      adapted from the Community Service Attitude Inventory. For the entire sample,
      caregivers and care recipients had similar attitude scores at the group level of
      comparison. In the caregiver subsample, female spousal caregivers reported a
      higher level of confidence in service system compared with male spousal
      caregivers. Male spousal caregivers reported a higher worry and fear attitude
      compared with female spousal caregivers. In the care recipient subsample, female
      spousal care recipients reported a higher wait-and-see attitude compared Volume
      26 Number 2 2007 with male spousal care recipients. The findings support the need
      to assess specific gender-related service use attitudes of older spousal couples
      in research and practice contexts.

PMID- 17537709
TI  - Can't they get anything better? Home support workers call for change.
AB  - A descriptive exploratory study examined the demographic characteristics and
      working conditions of home support workers in one Canadian province. Four hundred
      and sixty-three workers, a response rate of 43.5%, completed the Home Support
      Worker Survey, an instrument designed for the purposes of the study. Workers
      identified a need for changes to their working conditions including better wages,
      improved benefits, and a modified work schedule. Since these workers are the
      largest segment of formal care providers and the mainstay of formal support
      services for chronically ill seniors, attention to their issues is critical to
      the sustainability of the home care industry.

PMID- 17537710
TI  - Exploring influences on community-based case managers' advance care planning
      practices: facilitators or barriers?
AB  - Community-based geriatric case managers work with an increasingly frail older
      population in need of advance care planning throughout the end of life. However,
      little is known regarding factors that influence their professional practices in
      this area. This qualitative study used four focus groups to explore case
      managers' (N = 27) perceptions of facilitators and barriers to advance care
      planning practices. Themes from the study suggest that case managers view five
      key influences that appear to either assist or impede practices, depending on
      case manager's perceptions and experiences. Themes include: (1) Paradox of case
      management and programmatic realities; (2) extent of family presence and
      involvement; (3) level of proficiency in advance care planning; (4) degree of
      client receptivity to planning; and (5) limited communication with providers. The
      findings suggest that case managers vary in their advance care planning practices
      by differing perceptions regarding clients, families, professional expertise,
      program effects, and communication within the network of providers. More research
      is needed to clarify the factors associated with case managers' divergent advance
      care planning practices in order to enhance professional practice in this area.

PMID- 17537711
TI  - Older carers in ageing societies:an evaluation of a respite care program for
      older carers in Western Australia.
AB  - The Australian Red Cross Older Carers Program was developed in 2003 to support
      the unique needs of "older carers" aged 65 and older (50 if Indigenous) who care
      for a person (a care recipient, usually a family member) aged 18 or older who
      have a permanent disability. The aim of the program was to provide intensive case
      planning, management, and volunteer support that would assist older carers to
      more readily access respite and continue their caring role in the home. To help
      achieve this end, ongoing individualised and holistic assistance involving older
      carers in decision making was an integral component of the Older Carers Program,
      as was the use of regular home visits by program staff. The Older Carers Program
      evaluation was both a process and outcome evaluation. Much of the evaluation
      research focused on the extent to which it had met its stated aims and
      objectives. However, because the program was quite new and innovative there was a
      significant further focus upon the processes and activities within the program.
      At the time the evaluation research was conducted (May 2005), the program had
      been in operation for 22 months. The population group was identified as those
      persons (older carers) who had been part of the program between July 2003 and
      March 2005. Of the 96 older carers who had accessed the program in the specified
      period, 62 agreed to participate in our research. The methodology consisted of an
      audit or the program database, in-depth interviews with older carers, and
      contextual data collection involving program staff and other stakeholders.

PMID- 17537712
TI  - Evaluating the outcomes of gerontological curriculum enrichment:a multi-method
      approach.
AB  - This study describes a multi-method approach to evaluating a gerontological
      social work curriculum enrichment initiative funded by the John A. Hartford
      Foundation. The project involved all required first year core courses in the BA
      and MSW curricula. Data were collected from students at three geographically
      dispersed academic centers of a School of Social Work at a major Midwestern state
      university. Evaluation instruments included quantitative pre- and post-tests to
      assess change in undergraduate and graduate students' gerontological attitudes,
      knowledge, and skills, qualitative and quantitative pre- and post- tests to
      evaluate an intergenerational service-learning option, and an open ended question
      to assess the gerontological content students had been exposed to in required
      core courses. Results for all students showed strong positive change in general
      attitudes toward elders, gerontological knowledge, and gerontological skills.
      There was only marginal support, however, for increased willingness to work with
      elders. Results for service learning students revealed positive reactions to the
      service-learning experience and a significant increase in gerontological
      knowledge.

PMID- 17537713
TI  - The impact of gerontology inclusion on 12th grade student perceptions of aging,
      older adults and working with elders.
AB  - The present study examines the impact of including lessons on aging in a 12th
      grade social studies course on student perceptions of aging and older adults,
      working with older persons, and knowledge of "facts" on aging. Pre/post-test data
      were collected from approximately 650 upstate New York 12th grade students
      enrolled in a government class that included from five to ten lessons on aging
      issues. Over two-thirds of the semantic differential and four of five job-related
      questions showed a significant change to more positive views of aging. Changes on
      the "fact" questions were mixed but students uniformly reported that the
      interview with an older adult assignment changed their view of the older person
      with whom they talked and was the most popular activity in the unit. These
      findings suggest that including information on aging in a high school social
      studies course can lead to more positive student perceptions of aging and general
      attitudes toward working with older adults.

PMID- 17537714
TI  - Health contract in the classroom.
AB  - A health contract is a technique used by health professionals to help clients
      achieve a health goal. This article describes a course, "Changing Health
      Behaviors," in which a health contract strategy is taught and practiced with
      older adults. The health contract can also be included as a smaller educational
      component within a gerontology course that covers risk factors such as sedentary
      behavior or nutritional deficiency, counseling or health education techniques, or
      program development. Gerontology students who complete a degree or certificate
      program may enter a variety of venues in which a health contract can be a useful
      tool with older clients.

PMID- 17537715
TI  - Lighting the match:using haiku to teach about aging.
AB  - The purpose of this article is to describe an innovative teaching method in which
      American undergraduate students were asked to write haiku--a Japanese poetry form
      -about the lives of nursing home residents. Drawing on both their own experiences
      and May Sarton's novel As We Are Now, class members created poems about
      institutionalization that exhibited descriptive, analytic and reflective
      qualities. Since Sarton's central character, Caroline Spencer, eventually burns
      down the facility where she has been consigned--setting what she herself calls a
      "cleansing holocaust"--students were also asked to address the question: Did she
      have the right to do it? Their responses expressed themes of compassion,
      condemnation, and moral ambiguity. Numerous examples of the poems produced by the
      students are provided to show how they struggled with and used the concise
      framework of haiku to explore their own insights, emotions, and ethical values
      about aging, power and institutionalization.

PMID- 17537716
TI  - Part-time faculty and gerontology programs:dilemmas and solutions.
AB  - This article presents an overview of the use of adjunct faculty generally and
      within gerontology programs and discusses the benefits, drawbacks and possible
      solutions for both adjunct faculty and gerontology programs to utilize part-time
      teaching staff. The benefits reported for being a part-time faculty member
      include wanting to be in academia and supplementing an income. The reasons
      gerontology programs hire adjunct faculty members include their being less costly
      and bringing new skills to the programs. There are also practical and substantive
      drawbacks faced by part-time faculty. Practical issues include confusion with the
      pay schedule and last-minute class cancellations. Substantive issues include a
      lack of both respect and opportunities for professional development. The
      solutions to these issues include assigned space and support to part-time faculty
      members, maintaining peer and student evaluations, and affirming diversity in
      gerontology by recruiting adjunct faculty with knowledge and research
      capabilities for tenure-track positions as a strategy for successful gerontology
      program development.

PMID- 17537717
TI  - The use of the internet in geriatrics education: results of a national survey of
      medical geriatrics academic programs.
AB  - In order to characterize use of the Internet in medical geriatrics education
      programs, 130 medical education programs in the U.S. that train medical students,
      interns, residents, fellows and practicing physicians were asked to complete a
      survey developed by the Consortium of E-Learning in Geriatrics Instruction
      (CELGI). Sixty-eight programs (52.3%) returned surveys. Fifty-four (79%) of those
      responding reported using the Internet specifically for geriatric medical
      education, and 38 (56%) reported they are developing Internet materials.
      Twentythree undergraduate, 31 graduate, and 26 continuing medical education
      programs reported at least 25% of their curriculum was Internet-based. Users and
      developers of medical geriatric Internet materials had more full-time faculty and
      nonclinical faculty. The results of our survey indicate that the Internet is
      being widely used in medical geriatric education.

PMID- 17537718
TI  - Design and evaluation in eHealth: challenges and implications for an
      interdisciplinary field.
AB  - Much has been written about insufficient user involvement in the design of
      eHealth applications, the lack of evidence demonstrating impact, and the
      difficulties these bring for adoption. Part of the problem lies in the differing
      languages, cultures, motives, and operational constraints of producers and
      evaluators of eHealth systems and services. This paper reflects on the benefits
      of and barriers to interdisciplinary collaboration in eHealth, focusing
      particularly on the relationship between software developers and health services
      researchers. It argues that the common pattern of silo or parallel working may be
      ameliorated by developing mutual awareness and respect for each others' methods,
      epistemologies, and contextual drivers and by recognizing and harnessing
      potential synergies. Similarities and differences between models and techniques
      used in both communities are highlighted in order to illustrate the potential for
      integrated approaches and the strengths of unique paradigms. By sharing
      information about our research approaches and seeking to actively collaborate in
      the process of design and evaluation, the aim of achieving technologies that are
      truly user-informed, fit for context, high quality, and of demonstrated value is
      more likely to be realized. This may involve embracing new ways of working
      jointly that are unfamiliar to the stakeholders involved and that challenge
      disciplinary conventions. It also has policy implications for agencies
      commissioning research and development in this area.

PMID- 17537719
TI  - In vitro synthesis of oleoylglycine by cytochrome c points to a novel pathway for
      the production of lipid signaling molecules.
AB  - Long chain fatty acyl glycines represent a new class of signaling molecules whose
      biosynthetic pathway is unknown. Here we report that cytochrome c catalyzes the
      formation of oleoylglycine from oleoyl-CoA and glycine, in the presence of
      hydrogen peroxide. The identity of oleoylglycine product was confirmed by isotope
      labeling and fragmentation mass spectrometry. Synthesis of oleoylglycine by
      cytochrome c was dependent upon substrate concentration and time. Other heme
      containing proteins, myoglobin and hemoglobin, did not catalyze oleoylglycine
      synthesis. The functional properties of the reaction closely resemble those
      observed for the ability of cytochrome c to mediate the synthesis of oleamide
      from oleoyl-CoA and ammonia, in the presence of hydrogen peroxide (Driscoll, W.
      J., Chaturvedi., S., and Mueller, G. P. (2007) J. Biol. Chem. 282). The ability
      of cytochrome c to catalyze the formation of oleoylglycine experimentally
      indicates the potential importance of cytochrome c as a novel mechanism for the
      generation of long chain fatty acyl glycine messengers in vivo.

PMID- 17537720
TI  - A potential dimerization region of dCAMTA is critical for termination of fly
      visual response.
AB  - CAMTAs are a group of Ca(2+)/calmodulin binding transcription activators that are
      implicated in brain tumor suppression, cardiac hypertrophy, and plant sensory
      responses. The sole fly CAMTA, dCAMTA, stimulates expression of an F-box gene,
      dFbxl4, to potentiate rhodopsin deactivation, which enables rapid termination of
      fly visual responses. Here we report that a dCAMTA fragment associated with a
      full-length protein in co-transfected human embryonic kidney 293 cells. The
      interaction site was mapped to a region within the DNA-binding CG-1 domain. With
      this potential dimerization site mutated, the full-length dCAMTA had defective
      nuclear localization. In transgenic flies, this mutant dCAMTA variant failed to
      stimulate expression of dFbxl4 and rescue the slow termination of light response
      phenotype of a dCAMTA null mutant fly. Our data suggest that dCAMTA may function
      as a dimer during fly visual regulation and that the CG-1 domain may mediate
      dimerization of CAMTA transcription factors.

PMID- 17537721
TI  - Targeting host cell furin proprotein convertases as a therapeutic strategy
      against bacterial toxins and viral pathogens.
AB  - Pathogens or their toxins, including influenza virus, Pseudomonas, and anthrax
      toxins, require processing by host proprotein convertases (PCs) to enter host
      cells and to cause disease. Conversely, inhibiting PCs is likely to protect host
      cells from multiple furin-dependent, but otherwise unrelated, pathogens. To
      determine if this concept is correct, we designed specific nanomolar inhibitors
      of PCs modeled from the extended cleavage motif TPQRERRRKKR downward arrowGL of
      the avian influenza H5N1 hemagglutinin. We then confirmed the efficacy of the
      inhibitory peptides in vitro against the fluorescent peptide, anthrax protective
      antigen (PA83), and influenza hemagglutinin substrates and also in mice in vivo
      against two unrelated toxins, anthrax and Pseudomonas exotoxin. Peptides with
      Phe/Tyr at P1' were more selective for furin. Peptides with P1' Thr were potent
      against multiple PCs. Our strategy of basing the peptide sequence on a furin
      cleavage motif known for an avian flu virus shows the power of starting inhibitor
      design with a known substrate. Our results confirm that inhibiting furin-like PCs
      protects the host from the distinct furin-dependent infections and lay a
      foundation for novel, host cell-focused therapies against acute diseases.

PMID- 17537722
TI  - Mitofusin 2 protects cerebellar granule neurons against injury-induced cell
      death.
AB  - Of the GTPases involved in the regulation of the fusion machinery, mitofusin 2
      (Mfn2) plays an important role in the nervous system as point mutations of this
      isoform are associated with Charcot Marie Tooth neuropathy. Here, we investigate
      whether Mfn2 plays a role in the regulation of neuronal injury. We first examine
      mitochondrial dynamics following different modes of injury in cerebellar granule
      neurons. We demonstrate that neurons exposed to DNA damage or oxidative stress
      exhibit extensive mitochondrial fission, an early event preceding neuronal loss.
      The extent of mitochondrial fragmentation and remodeling is variable and depends
      on the mode and the severity of the death stimuli. Interestingly, whereas
      mitofusin 2 loss of function significantly induces cell death in the absence of
      any cell death stimuli, expression of mitofusin 2 prevents cell death following
      DNA damage, oxidative stress, and K+ deprivation induced apoptosis. More
      importantly, whereas wild-type Mfn2 and the hydrolysis-deficient mutant of Mfn2
      (Mfn2(RasG12V)) function equally to promote fusion and lengthening of
      mitochondria, the activated Mfn2(RasG12V) mutant shows a significant increase in
      the protection of neurons against cell death and release of proapoptotic factor
      cytochrome c. These findings highlight a signaling role for Mfn2 in the
      regulation of apoptosis that extends beyond its role in mitochondrial fusion.

PMID- 17537723
TI  - The p21-activated kinase 3 implicated in mental retardation regulates spine
      morphogenesis through a Cdc42-dependent pathway.
AB  - The p21-activated kinase 3 (PAK3) is one of the recently identified genes for
      which mutations lead to nonsyndromic mental retardation. PAK3 is implicated in
      dendritic spine morphogenesis and is a key regulator of synaptic functions.
      However, the underlying roles of PAK3 in these processes remain poorly
      understood. We report here that the three mutations R419X, A365E, and R67C,
      responsible for mental retardation have different effects on the biological
      functions of PAK3. The R419X and A365E mutations completely abrogate the kinase
      activity. The R67C mutation drastically decreases the binding of PAK3 to the
      small GTPase Cdc42 and impairs its subsequent activation by this GTPase. We also
      report that PAK3 binds significantly more Cdc42 than Rac1 and is selectively
      activated by endogenous Cdc42, suggesting that PAK3 is a specific effector of
      Cdc42. Interestingly, the expression of the three mutated proteins in hippocampal
      neurons affects spinogenesis differentially. Both kinase-dead mutants slightly
      decrease the number of spines but profoundly alter spine morphology, whereas
      expression of the R67C mutant drastically decreases spine density. These results
      demonstrate that the Cdc42/PAK3 is a key module in dendritic spine formation and
      synaptic plasticity.

PMID- 17537724
TI  - Tumor progression locus-2 is a critical regulator of pancreatic and lung
      inflammation during acute pancreatitis.
AB  - Pancreatic and lung inflammation during acute pancreatitis is a poorly
      understood, but clinically important, phenomenon. The proto-oncogene Tpl2 (tumor
      progression locus-2) has recently been shown to have important immunomodulatory
      effects on some inflammatory processes, but its importance to pancreatitis has
      not been previously examined. Our studies were designed to (a) define the effects
      of Tpl2 on pancreatic and lung inflammation during pancreatitis and (b) identify
      mechanisms and cell types responsible for those effects. We examined pancreatitis
      associated Tpl2 effects in wild type and Tpl2(-/-) mice subjected to either
      secretagogue-induced or bile salt-induced pancreatitis. To determine the myeloid
      or non-myeloid lineage of cells responsible for the Tpl2 effects, we used Tpl2(-/
      ) chimeric mice generated by lethal irradiation followed by bone marrow
      transplantation. Mechanisms responsible for the effects of Tpl2 ablation on
      caerulein-induced proinflammatory events were evaluated under in vivo and in
      vitro conditions using the techniques of electrophoretic mobility shift assay,
      immunoblot analysis, and quantitative reverse transcription-PCR. We found that
      Tpl2 ablation markedly reduced pancreatic and lung inflammation in these two
      dissimilar models of pancreatitis, but it did not alter pancreatic
      injury/necrosis in either model. The reduction in caerulein-induced pancreatic
      inflammation is dependent upon Tpl2 ablation in non-myeloid cells and is
      associated with both in vivo and in vitro inhibition of MEK, JNK, and AP-1
      activation and the expression of MCP-1, MIP-2, and interleukin-6. Non-myeloid
      cell expression of Tpl2 regulates pancreatic inflammation during pancreatitis by
      mediating proinflammatory signals and the generation of neutrophil
      chemoattracting factors.

PMID- 17537725
TI  - Substrate-specific interactions with the heme-bound oxygen molecule of nitric
      oxide synthase.
AB  - We report the characterization by resonance Raman spectroscopy of the oxygenated
      complex (Fe(II)O(2)) of nitric-oxide synthases of Staphylococcus aureus (saNOS)
      and Bacillus subtilis (bsNOS) saturated with N(omega)-hydroxy-l-arginine. The
      frequencies of the nu(Fe-O) and nu(O-O) modes were 530 and 1135 cm(-),
      respectively, in both the presence and absence of tetrahydrobiopterin. On the
      basis of a comparison of these frequencies with those of saNOS and bsNOS
      saturated with l-arginine (nu(Fe-O) at 517 cm(-1) and nu(O-O) at 1123 cm(-1)) and
      those of substrate-free saNOS (nu(Fe-O) at 517 and nu(O-O) at 1135 cm(-1))
      (Chartier, F. J. M., Blais, S. P., and Couture, M. (2006) J. Biol. Chem. 281,
      9953-9962), we propose two models that account for the frequency shift of nu(Fe
      O) (but not nu(O-O)) upon N(omega)-hydroxy-l-arginine binding as well as the
      frequency shift of nu(O-O) (but not nu(Fe-O)) upon l-arginine binding. The
      implications of these substrate-specific interactions with respect to catalysis
      by NOSs are discussed.

PMID- 17537726
TI  - The melanization reaction is not required for survival of Anopheles gambiae
      mosquitoes after bacterial infections.
AB  - The melanization reaction of insects requires activation of pro-phenoloxidase by
      a proteolytic cascade leading to melanin production. Studies in adult mosquitoes
      have shown that bacteria are efficiently melanized in the hemocoel, but the
      contribution of melanization to survival after bacterial infections has not been
      established. Here we show that the Anopheles gambiae noncatalytic serine protease
      CLIPA8, an essential factor for Plasmodium ookinete melanization, is also
      required for melanization of bacteria in adult mosquitoes. CLIPA8 silencing by
      RNA interference inhibits pro-phenoloxidase activation and melanization of
      bacteria in the hemolymph following microbial challenge. However, CLIPA8 is not
      required for wound melanization nor for melanotic pseudotumor formation in
      serpin2 knockdown mosquitoes, suggesting a specific role for pathogen
      melanization. Surprisingly, CLIPA8 knockdown mosquitoes are as resistant to
      bacterial challenge as controls, indicating that melanization is not essential
      for defense against bacteria and questions its precise role in mosquito immunity.

PMID- 17537727
TI  - Short-term treatment of RAW264.7 macrophages with adiponectin increases tumor
      necrosis factor-alpha (TNF-alpha) expression via ERK1/2 activation and Egr-1
      expression: role of TNF-alpha in adiponectin-stimulated interleukin-10
      production.
AB  - Adiponectin is an adipokine with potent anti-inflammatory properties. However,
      the mechanisms by which adiponectin suppresses macrophage function are not well
      understood. Treatment of RAW264.7 macrophages with adiponectin for 18 h decreased
      lipopolysaccharide (LPS)-stimulated tumor necrosis factor-alpha (TNF-alpha)
      production. Here we demonstrate that globular adiponectin (gAcrp) initially
      increased TNF-alpha expression in RAW264.7 macrophages; this TNF-alpha then
      contributed to increased expression of interleukin-10, which in turn was required
      for the development of tolerance to subsequent LPS exposure. gAcrp-mediated
      increases in TNF-alpha mRNA accumulation were associated with increased TNF-alpha
      promoter activity. gAcrp increased the DNA binding activity of both Egr-1 and
      NFkappaB; mutation of either the Egr-1 or NFkappaB binding sites in the TNF-alpha
      promoter decreased gAcrp-stimulated promoter activity. Further, co-transfection
      with either dominant negative Egr-1 or the IkappaB super-repressor prevented
      gAcrp-stimulated TNF-alpha promoter activity. gAcrp also increased Egr-1 promoter
      activity, mRNA accumulation, and DNA binding activity. Inhibition of ERK1/2 with
      U0126 potently suppressed gAcrp-stimulated Egr-1 promoter activity, as well as
      TNF-alpha promoter activity. In summary, these data demonstrate that adiponectin
      initially increases TNF-alpha production by macrophages via ERK1/2-->Egr-1 and
      NFkappaB-dependent mechanisms; these increases in TNF-alpha in turn lead to
      increased expression of interleukin-10 and an eventual dampening of LPS-mediated
      cytokine production in macrophages.

PMID- 17537728
TI  - Bacillus thuringiensis Cry1Ab mutants affecting oligomer formation are non-toxic
      to Manduca sexta larvae.
AB  - Pore-forming toxins are biological weapons produced by a variety of living
      organisms, particularly bacteria but also by insects, reptiles, and
      invertebrates. These proteins affect the cell membrane of their target,
      disrupting permeability and leading eventually to cell death. The pore-forming
      toxins typically transform from soluble, monomeric proteins to oligomers that
      form transmembrane channels. The Cry toxins produced by Bacillus thuringiensis
      are widely used as insecticides. These proteins have been recognized as pore
      forming toxins, and their primary action is to lyse midgut epithelial cells in
      their target insect. To exert their toxic effect, a prepore oligomeric
      intermediate is formed leading finally to membrane-inserted oligomeric pores. To
      understand the role of Cry oligomeric pre-pore formation in the insecticidal
      activity we isolated point mutations that affected toxin oligomerization but not
      their binding with the cadherin-like, Bt-R(1) receptor. We show the helix alpha-3
      in domain I contains sequences that could form coiled-coil structures important
      for oligomerization. Some single point mutants in this helix bound Bt-R(1)
      receptors with similar affinity as the wild-type toxin, but were affected in
      oligomerization and were severally impaired in pore formation and toxicity
      against Manduca sexta larvae. These data indicate the pre-pore oligomer and the
      toxin pore formation play a major role in the intoxication process of Cry1Ab
      toxin in insect larvae.

PMID- 17537729
TI  - Free oligosaccharides in the cytosol of Caenorhabditis elegans are generated
      through endoplasmic reticulum-golgi trafficking.
AB  - Free oligosaccharides (FOSs) in the cytosol of eukaryotic cells are mainly
      generated during endoplasmic reticulum (ER)-associated degradation (ERAD) of
      misfolded glycoproteins. We analyzed FOS of the nematode Caenorhabditis elegans
      to elucidate its detailed degradation pathway. The major FOSs were high mannose
      type ones bearing 3-9 Man residues. About 94% of the total FOSs had one GlcNAc at
      their reducing end (FOS-GN1), and the remaining 6% had two GlcNAc (FOS-GN2). A
      cytosolic endo-beta-N-acetylglucosaminidase mutant (tm1208) accumulated FOS-GN2,
      indicating involvement of the enzyme in conversion of FOS-GN2 into FOS-GN1. The
      most abundant FOS in the wild type was Man(5)GlcNAc(1), the M5A' isomer
      (Manalpha1-3(Manalpha1-6)Manalpha1-6(Manalpha1-3)Manbeta1-4GlcNAc), which is
      different from the corresponding M5B' (Manalpha1-2Manalpha1-2Manalpha1
      3(Manalpha1-6)Manbeta1-4GlcNAc) in mammals. Analyses of FOS in worms treated with
      Golgi alpha-mannosidase I inhibitors revealed decreases in Man(5)GlcNAc(1) and
      increases in Man(7)GlcNAc(1). These results suggested that Golgi alpha
      mannosidase I-like enzyme is involved in the production of Man(5-6)-GlcNAc(1),
      which is unlike in mammals, in which cytosolic alpha-mannosidase is involved.
      Thus, we assumed that major FOSs in C. elegans were generated through Golgi
      trafficking. Analysis of FOSs from a Golgi alpha-mannosidase II mutant (tm1078)
      supported this idea, because GlcNAc(1)Man(5)GlcNAc(1), which is formed by the
      Golgi-resident GlcNAc-transferase I, was found as a FOS in the mutant. We
      concluded that significant amounts of misfolded glycoproteins in C. elegans are
      trafficked to the Golgi and are directly or indirectly retro-translocated into
      the cytosol to be degraded.

PMID- 17537730
TI  - Inhibition of a specific N-glycosylation activity results in attenuation of
      breast carcinoma cell invasiveness-related phenotypes: inhibition of epidermal
      growth factor-induced dephosphorylation of focal adhesion kinase.
AB  - Changes in the expression of glycosyltransferases that branch N-linked glycans
      can alter the function of several types of cell surface receptors and a glucose
      transporter. To study in detail the mechanisms by which aberrant N-glycosylation
      caused by altered N-acetylglucosaminyltransferase V(GnT-V, GnT-Va, and Mgat5a)
      expression can regulate the invasiveness-related phenotypes found in some
      carcinomas, we utilized specific small interfering RNA (siRNA) to selectively
      knock down GnT-V expression in the highly metastatic and invasive human breast
      carcinoma cell line, MDA-MB231. Knockdown of GnT-V by siRNA expression had no
      effect on epidermal growth factor receptor expression levels but lowered
      expression of N-linked beta(1,6)-branching on epidermal growth factor receptor,
      as expected. Compared with control cells, knockdown of GnT-V caused significant
      inhibition of the morphological changes and cell detachment from matrix that is
      normally seen after stimulation with epidermal growth factor (EGF). Decreased
      expression of GnT-V caused a marked inhibition of EGF-induced dephosphorylation
      of focal adhesion kinase (FAK), consistent with the lack of cell morphology
      changes in the cells expressing GnT-V siRNA. The attenuation of EGF-mediated
      phosphorylation and activation of the tyrosine phosphatase SHP-2 was dramatically
      observed in GnT-V knockdown cells, and these effects could be rescued by
      reintroduction of GnT-V into these cells, indicating that reduced EGF-mediated
      activation of SHP-2 was GnT-V related. Concomitantly, knockdown of GnT-V caused
      reduced EGF-mediated ERK signaling and tumor cell invasiveness-related
      phenotypes, including effects on actin rearrangement and cell motility. No
      changes in EGF binding were observed, however, after knockdown of GnT-V. Our
      results demonstrate that decreased GnT-V activity due to siRNA expression in
      human breast carcinoma cells resulted in an inhibition of EGF-stimulated SHP-2
      activation and, consequently, caused attenuation of the dephosphorylation of FAK
      induced by EGF. These effects suppressed EGF-mediated downstream signaling and
      invasiveness-related phenotypes and suggest GnT-V as a potential therapeutic
      target.

PMID- 17537731
TI  - Promoter-dependent effect of IKKalpha on NF-kappaB/p65 DNA binding.
AB  - IKKalpha regulates many chromatin events in the nuclear phase of the NF-kappaB
      program, including phosphorylation of histone H3 and removal of co-repressors
      from NF-kappaB-dependent promoters. However, all of the nuclear functions of
      IKKalpha are not understood. In this study, using mouse embryonic fibroblasts
      IKKalpha knock-out and reexpressing IKKalpha after retroviral transduction, we
      demonstrate that IKKalpha contributes to NF-kappaB/p65 DNA binding activity on an
      exogenous kappaB element and on some, but not all, endogenous NF-kappaB-target
      promoters. Indeed, p65 chromatin immunoprecipitation assays revealed that
      IKKalpha is crucial for p65 binding on kappaB sites of icam-1 and mcp-1 promoters
      but not on ikappabalpha promoter. The mutation of IKKalpha putative nuclear
      localization sequence, which prevents its nuclear translocation, or of crucial
      serines in the IKKalpha activation loop completely inhibits p65 binding on icam-1
      and mcp-1 promoters and rather enhances p65 binding on the ikappabalpha promoter.
      Further molecular studies demonstrated that the removal of chromatin-bound HDAC3,
      a histone deacetylase inhibiting p65 DNA binding, is differentially regulated by
      IKKalpha in a promoter-specific manner. Indeed, whereas the absence of IKKalpha
      induces HDAC3 recruitment and repression on the icam-1 promoter, it has an
      opposite effect on the ikappabalpha promoter, where a better p65 binding occurs.
      We conclude that nuclear IKKalpha is required for p65 DNA binding in a gene
      specific manner.

PMID- 17537732
TI  - Structure of phenylalanine hydroxylase from Colwellia psychrerythraea 34H, a
      monomeric cold active enzyme with local flexibility around the active site and
      high overall stability.
AB  - The characteristic of cold-adapted enzymes, high catalytic efficiency at low
      temperatures, is often associated with low thermostability and high flexibility.
      In this context, we analyzed the catalytic properties and solved the crystal
      structure of phenylalanine hydroxylase from the psychrophilic bacterium Colwellia
      psychrerythraea 34H (CpPAH). CpPAH displays highest activity with
      tetrahydrobiopterin (BH(4)) as cofactor and at 25 degrees C (15 degrees C above
      the optimal growth temperature). Although the enzyme is monomeric with a single L
      Phe-binding site, the substrate binds cooperatively. In comparison with PAH from
      mesophilic bacteria and mammalian organisms, CpPAH shows elevated [S(0.5)](L-Phe)
      (= 1.1 +/- 0.1 mm) and K(m)(BH(4))(= 0.3 +/- 0.1 mm), as well as high catalytic
      efficiency at 10 degrees C. However, the half-inactivation and denaturation
      temperature is only slightly lowered (T(m) approximately 52 degrees C; where T(m)
      is half-denaturation temperature), in contrast to other cold-adapted enzymes. The
      crystal structure shows regions of local flexibility close to the highly solvent
      accessible binding sites for BH(4) (Gly(87)/Phe(88)/Gly(89)) and l-Phe (Tyr(114)
      Pro(118)). Normal mode and COREX analysis also detect these and other areas with
      high flexibility. Greater mobility around the active site and disrupted hydrogen
      bonding abilities for the cofactor appear to represent cold-adaptive properties
      that do not markedly affect the thermostability of CpPAH.

PMID- 17537733
TI  - Structural basis of LSD1-CoREST selectivity in histone H3 recognition.
AB  - Histone demethylase LSD1 regulates transcription by demethylating Lys(4) of
      histone H3. The crystal structure of the enzyme in complex with CoREST and a
      substrate-like peptide inhibitor highlights an intricate network of interactions
      and a folded conformation of the bound peptide. The core of the peptide structure
      is formed by Arg(2), Gln(5), and Ser(10), which are engaged in specific
      intramolecular H-bonds. Several charged side chains on the surface of the
      substrate-binding pocket establish electrostatic interactions with the peptide.
      The three-dimensional structure predicts that methylated Lys(4) binds in a
      solvent inaccessible position in front of the flavin cofactor. This geometry is
      fully consistent with the demethylation reaction being catalyzed through a flavin
      mediated oxidation of the substrate amino-methyl group. These features dictate
      the exquisite substrate specificity of LSD1 and provide a structural framework to
      explain the fine tuning of its catalytic activity and the active role of CoREST
      in substrate recognition.

PMID- 17537734
TI  - Janus kinase 3 regulates interleukin 2-induced mucosal wound repair through
      tyrosine phosphorylation of villin.
AB  - Janus kinase 3 (Jak3) is a non-receptor tyrosine kinase known to be expressed in
      hematopoietic cells. Studies of whole organ homogenates show that Jak3 is also
      expressed in the intestines of both human and mice. However, neither its
      expression nor its function has been defined in intestinal epithelial
      enterocytes. The present studies demonstrate that functional Jak3 is expressed in
      human intestinal enterocytes HT-29 Cl-19A and Caco-2 and plays an essential role
      in the intestinal epithelial wound repair process in response to interleukin 2
      (IL-2). Exogenous IL-2 enhanced the wound repair of intestinal enterocytes in a
      dose-dependent manner. Activation by IL-2 led to rapid tyrosine phosphorylation
      and redistribution of Jak3. IL-2-stimulated redistribution of Jak3 was inhibited
      by the Jak3-specific inhibitor WHI-P131. IL-2 also induced Jak3-dependent
      redistribution of the actin cytoskeleton in migrating cells. In these cells Jak3
      interacted with the intestinal and renal epithelial cell-specific cytoskeletal
      protein villin in an IL-2-dependent manner. Inhibition of Jak3 activation
      resulted in loss of tyrosine phosphorylation of villin and a significant decrease
      in wound repair of the intestinal epithelial cells. Previously, we had shown that
      tyrosine phosphorylation of villin is important for cytoskeletal remodeling and
      cell migration. The present study demonstrates a novel pathway in intestinal
      enterocytes in which IL-2 enhances intestinal wound repair through mechanisms
      involving Jak3 and its interactions with villin.

PMID- 17537735
TI  - Catalytic activity is not required for secreted PCSK9 to reduce low density
      lipoprotein receptors in HepG2 cells.
AB  - Proprotein convertase subtilisin/kexin type 9 (PCSK9), a member of the proteinase
      K subfamily of subtilases, promotes internalization and degradation of low
      density lipoprotein receptors (LDLRs) after binding the receptor on the surface
      of hepatocytes. PCSK9 has autocatalytic activity that releases the prodomain at
      the N terminus of the protein. The prodomain remains tightly associated with the
      catalytic domain as the complex transits the secretory pathway. It is not known
      whether enzymatic activity is required for the LDLR-reducing effects of PCSK9.
      Here we expressed the prodomain together with a catalytically inactive protease
      domain in cells and purified the protein from the medium. The ability of the
      catalytically inactive PCSK9 to bind and degrade LDLRs when added to culture
      medium of human hepatoma HepG2 cells at physiological concentrations was similar
      to that seen using wild-type protein. Similarly, a catalytic-dead version of a
      gain-of-function mutant, PCSK9(D374Y), showed no loss of activity compared with a
      catalytically active counterpart; both proteins displayed approximately 10-fold
      increased activity in degradation of cell surface LDLRs compared with wild-type
      PCSK9. We conclude that the ability of PCSK9 to degrade LDLRs is independent of
      catalytic activity and suggest that PCSK9 functions as a chaperone to prevent
      LDLR recycling and/or to target LDLRs for lysosomal degradation.

PMID- 17537736
TI  - Status and plans for implementation of NRC regulatory authority for certain
      naturally occurring and accelerator-produced radioactive material.

PMID- 17537737
TI  - Primary mural endocarditis.

PMID- 17537738
TI  - A propensity-matched study of the association of low serum potassium levels and
      mortality in chronic heart failure.
AB  - AIMS: Potassium homeostasis is essential for normal myocardial function, and low
      serum potassium may cause fatal arrhythmias. However, the association of low
      potassium and long-term mortality and morbidity in heart failure (HF) is largely
      unknown. METHODS AND RESULTS: We studied 6845 HF patients in the Digitalis
      Investigation Group trial with serum potassium levels < or =5.5 mEq/L. Of these,
      1189 had low potassium (<4 mEq/L). Propensity scores for low potassium were
      calculated for each patient and were used to match 1187 low-potassium patients
      with 1187 normal-potassium (4-5.5 mEq/L) patients. Effects of low potassium on
      outcomes were assessed using matched Cox regression analyses. All-cause mortality
      occurred in 379 (rate, 1103/10 000 person-years) normal-potassium and 441 (rate,
      1330/10 000 person-years) low-potassium patients, respectively, during 3437 and
      3315 years of follow-up [hazard ratio (HR), 1.25; 95% confidence interval (CI),
      1.07-1.46; P = 0.006]. Cardiovascular mortality occurred in 297 (864/10 000
      person-years) normal-potassium and 356 (1074/10 000 person-years) low-potassium
      patients (HR, 1.27; 95% CI, 1.06-1.51; P = 0.009). Cardiovascular hospitalization
      occurred in 610 (rate, 2553/10 000 person-years) normal-potassium and 637 (rate,
      2855/10 000 person-years) low-potassium patients (HR, 1.13; 95% CI, 0.99-1.29; P
      = 0.082). CONCLUSION: In a cohort of ambulatory chronic systolic and diastolic HF
      patients who were balanced in all measured baseline covariates, serum potassium
      <4 mEq/L was associated with increased mortality, with a trend towards increased
      hospitalization.

PMID- 17537739
TI  - Effectiveness of liaison psychiatric nursing in older medical inpatients with
      depression: a randomised controlled trial.
AB  - OBJECTIVE: To compare liaison psychiatric nursing with usual medical care in the
      management of older medical inpatients who screen positive for depression.
      DESIGN: Pragmatic randomised controlled trial. SETTING: Medical wards of UK
      district general hospital in rural East Anglia. PARTICIPANTS: One hundred and
      thirty-eight medical inpatients aged 65+ screened positive on the 15-item
      geriatric depression scale (GDS). One hundred and twenty-one out of 138 screen
      positives entered the trial (58/121 fulfilled criteria for depressive disorder at
      baseline). INTERVENTIONS: (i) A liaison psychiatric nurse assessed participants,
      formulated a care plan for treatment of their depression, ensured its
      implementation through liaison with appropriate agencies, and monitored
      participants' mood and response to treatment for up to 12 weeks. (ii) Usual
      treatment by hospital and primary care staff. MAIN OUTCOME MEASURES: ICD-10
      depressive disorder, change in GDS-15 score, quality-adjusted life weeks (QALWs)
      and patient satisfaction rating. RESULTS: Eighty-six out of 121 participants
      completed the 16-week trial. Participants in the intervention group were more
      satisfied with their care, but no significant differences in depressive disorder,
      depression rating or QALWs gained were found between groups. However, there was a
      trend towards improvement in the intervention group and effect sizes were higher
      in the subgroup with depressive disorder. CONCLUSIONS: This study is the first
      RCT to evaluate liaison psychiatric nursing specifically for depression in older
      medical inpatients; the findings suggest improvement in mental health and quality
      of life, but a larger trial is required to provide convincing evidence.

PMID- 17537740
TI  - Prevention of NSAID gastropathy in elderly patients. An observational study in
      general practice and nursing homes.
AB  - OBJECTIVES: The objectives of this study were to (i) survey the risk factors for
      NSAID gastropathy in outpatients (elderly patients in the community), compared to
      those living in old people's homes or nursing homes, (ii) study the prescription
      of medication prophylaxis during use of NSAIDs conform the current national
      guidelines and (iii) survey the influence on gastrointestinal symptoms and safety
      of pantoprazole 20 mg as prophylaxis for NSAID gastropathy. METHODS: Patients
      over 65 years of age, using an NSAID without prophylaxis or newly starting NSAID
      treatment were included in the study. Pantoprazole 20 mg was prescribed as
      prophylaxis. Patients using an NSAID with prophylaxis being a proton pump
      inhibitor at the first visit were registered for epidemiological reasons.
      Demographic data, risk factors, gastrointestinal complaints, and adverse events
      were collected at t = 0, t = 2 weeks, t = 3 months and t = 6 months. Differences
      between groups were analysed with Chi-square tests and Mann-Whitney U tests;
      changes in time in GI symptoms were tested using Wilcoxon signed ranks tests and
      McNemar tests. RESULTS: One hundred eighty one general practitioners (treating
      outpatients and patients in old people's homes)and five nursing home physicians
      participated in the study and a total of 615 patients were included (522 patients
      treated by general practitioners (GP) and 93 patients in nursing homes). Four
      hundred thirty two patients were using NSAIDs without prophylaxis or started
      using an NSAID at the first visit; 269 (62.1%) and 163 (37.9%) patients
      respectively. 65.3% of the outpatients (224 out of 343) did not receive indicated
      prophylaxis, versus 76.2% (16 out of 21) in old people's homes and 42.6% in
      nursing homes (29 out of 69) (P < 0.001). Patients in nursing homes had more risk
      factors for gastrointestinal complications (2.94 +/- 1.3 versus 1.77 +/- 0.9)
      than outpatients. More patients using an NSAID prior to the study complained of
      gastrointestinal symptoms compared to new users (P < 0.001). This seems to
      indicate that NSAIDs caused these symptoms. After 2 weeks of treatment with
      pantoprazole, there was no statistical difference between the two groups.
      Moreover, both groups showed improvement in complaints (P < 0.001). Only nine
      patients in the study population (3.1%) reported mild adverse events (e.g.
      nausea, headache) with an average of 1.1 adverse events per patient. Five
      patients (1% of the included population) died during the study period, but there
      was no relation to the NSAID or pantoprazole. DISCUSSION AND CONCLUSION: Patients
      in nursing homes had more risk factors for NSAID gastropathy than patients in old
      people's homes or outpatients (>65 years). Although in nursing homes co
      prescription of prophylaxis during NSAID use is more common, in general the Dutch
      guidelines on adequate NSAID use are still not fully implemented at this moment.
      The results also showed that pantoprazole was effective in diminishing
      gastrointestinal complaints, as well as preventing symptomatic NSAID gastropathy.
      Moreover, pantoprazole showed to be a safe and well-tolerated drug in our
      treatment group.

PMID- 17537741
TI  - Multi-modal exercise programs for older adults.
AB  - BACKGROUND: Various modalities of exercise have been demonstrated to improve
      physical function and quality of life in older adults. Current guidelines stress
      the importance of multi-modal exercise for this cohort, including strengthening
      exercises, cardiovascular, flexibility and balance training. There is a lack of
      evidence, however, that simultaneously prescribed doses and intensities of
      strength, aerobic, and balance training in older adults are both feasible and
      capable of eliciting changes in physical function and quality of life. METHODS: A
      comprehensive, systematic database search for manuscripts was performed. Two
      reviewers independently assessed studies for potential inclusion. Physical and
      functional performance outcomes were extracted. The relative effect sizes (ES)
      were calculated with 95% confidence intervals. RESULTS: Fifteen studies were
      included totalling 2,149 subjects; the mean cohort age ranging from 67 +/- 8 to
      84 +/- 3 years. A low mean relative ES for strength was seen across the reviewed
      studies. Only six of the eleven studies that included balance measurements found
      a significant improvement in balance compared to controls. Aerobic fitness was
      seldom measured or reported. Five out of the six studies investigating fall rates
      showed a significant reduction. Functional and quality of life measures generally
      did not improve with exercise. CONCLUSION: Multi-modal exercise has a positive
      effect on falls prevention. The limited data available suggests that multi-modal
      exercise has a small effect on physical, functional and quality of life outcomes.
      Future research should include robustly designed trials that involve multi-modal
      exercise at individually prescribed intensities based on doses found to be
      effective in single-modality studies.

PMID- 17537742
TI  - Serum high sensitivity C-reactive protein and cognitive function in elderly
      women.
AB  - BACKGROUND: Inflammation has been linked to cognitive impairment. However,
      limited data are available on the association between inflammatory markers and
      cognitive function. OBJECTIVES: We tested the hypothesis that elevated serum
      concentration of high sensitivity C-reactive protein (hs-CRP), an established
      marker of low-grade inflammation, predicts cognitive impairment in elderly women.
      DESIGN: A 12-year population-based follow-up study. PARTICIPANTS: A total of 97
      women between 60 and 70 years of age at baseline. METHODS: Serum hs-CRP
      concentration was measured by a high sensitivity assay. Global cognitive function
      was measured with the Mini-Mental State Examination (MMSE), and memory and
      cognitive speed were measured with a detailed cognitive test battery. RESULTS:
      Higher baseline hs-CRP was associated with poorer memory at 12-year follow-up
      without adjustment and after adjustment for age, education and depression
      (standardised regression coefficient beta -0.842, 95% confidence interval -1.602
      to -0.083, P = 0.030), and further adjustment for the use of hormone replacement
      therapy, smoking, serum LDL cholesterol and body mass index (standardised
      regression coefficient beta -0.817, 95% confidence interval -1.630 to -0.004, P =
      0.049). Memory at 12-year follow-up worsened linearly with increasing hs-CRP at
      baseline (P = 0.048 for linear trend). There was no association between hs-CRP at
      baseline and cognitive speed or MMSE score at 12-year follow-up. CONCLUSIONS:
      High serum hs-CRP concentration predicts poorer memory 12 years later in elderly
      women. Hs-CRP may be a useful biomarker to identify individuals at an increased
      risk for cognitive decline.

PMID- 17537743
TI  - C-reactive protein and delirium in acute ill elderly patients.

PMID- 17537744
TI  - Remitting seronegative symmetrical synovitis with pitting oedema associated with
      lung malignancy.
AB  - RS3PE syndrome is an inflammatory disease which affects mainly males and responds
      rapidly to low-dose steroids. We describe the concurrence of RS3PE and lung
      malignancy in a 78-year-old woman. We recommend that an underlying malignancy
      should always be excluded in patients with RS3PE syndrome, even when general
      signs and symptoms such as weight loss, anorexia and fever are absent or
      uncertain.

PMID- 17537745
TI  - Major depression among medically ill elders contributes to sustained poor mental
      health in their informal caregivers.
AB  - BACKGROUND: No longitudinal studies have addressed the effect of late life
      depression on the physical and mental health status of their informal caregivers.
      OBJECTIVE: To examine whether a diagnosis of depression in older medical
      inpatients is associated with the physical and mental health status of their
      informal caregivers after 6 months, independent of the physical health of the
      care recipient. DESIGN: Longitudinal observational study with 6-month follow-up.
      SETTING: Two Montreal acute-care hospitals. SUBJECTS: A sample of 97 cognitively
      intact medical inpatients aged 65 and over and their informal caregivers, with
      oversampling of patients with a diagnosis of major or minor depression. METHODS:
      Patient data included depression (current diagnosis, duration of current
      diagnosis, severity of symptoms, and history of depression), physical health
      (severity of illness, comorbidity, premorbid disability), and cognitive
      impairment. Caregiver data included relationship to patient, co-residence, and
      the physical and mental health status subscales of the SF-36. Multivariate linear
      regression analyses were conducted to determine the relationship between patient
      depression and caregiver 6 month SF-36 physical and mental scores, adjusting for
      baseline values, patient comorbidity, disability, and other patient and caregiver
      variables. RESULTS: Patient characteristics included: mean age 79.3, 62% female,
      46% major depression, 18% minor depression, 36% no depression. Caregiver
      characteristics included: 73% female, 35% co-resident spouse, 15% other co
      resident relation, 50% not residing with the patient. Results of the multivariate
      analyses showed that in comparison with caregivers of patients without a current
      diagnosis of depression, caregivers of those with major depression had a lower
      mental health score at follow-up (-9.54, 95% CI -16.66, -2.43), even though their
      physical health was slightly better (5.42 95% CI 0.04, 10.81). CONCLUSIONS: A
      diagnosis of major depression in older medical inpatients is independently
      associated with poor mental health in their informal caregivers 6 months later.

PMID- 17537746
TI  - Increased use of antidepressants at the end of life: population-based study among
      people aged 65 years and above.
AB  - BACKGROUND: The new antidepressants are generally effective and safe for older
      people, but may have serious side-effects. The use has been rapidly increasing,
      but focus on upper age groups has been limited. The pattern of antidepressant use
      as death approaches has never been analysed. OBJECTIVE: To analyse the use of
      antidepressants among individuals aged 65 years and above with respect to time
      trends, age and proximity to death. DESIGN: Population-based prescription study.
      SETTING: The County of Funen, Denmark, 1992-2004 (approximately 470,000
      inhabitants). RESULTS: The 1-year prevalence of antidepressants increases
      steadily over time in all age groups. Among the 65+ year-olds it also increases
      with age and differs substantially between the youngest and the oldest. Very high
      prevalences are observed: 26.8% among females 85-89 years old and 17.5% among
      males 85 years and above in 2004. In all age groups the use of antidepressants
      increases substantially with proximity to death in the last 3 years of life. In
      the last phase of life the use is independent of whether the patient dies at age
      65 or 90 about 33% of females and 25% of males receive antidepressants in the
      last 6 months. CONCLUSIONS: The use of antidepressants among 65+ year-olds
      increases with age and proximity to death to very high levels. Future studies may
      clarify the problems and diagnoses giving rise to the use of antidepressants for
      such a large proportion of older people, and especially the problems giving rise
      to treatment as death approaches.

PMID- 17537747
TI  - Cross-cultural validation of the London Handicap Scale and comparison of handicap
      perception between Chinese and UK populations.
AB  - OBJECTIVE: To validate the London Handicap Scale on populations from diverse
      cultures by comparing handicap perceptions in Mainland (Sichuan) Chinese, Hong
      Kong Chinese and UK subjects. METHOD: Utility ratings of 10 real life health
      scenarios were given by a group of healthy and disabled Sichuan Chinese subjects.
      The ratings were then correlated with published scale scores of HK and UK
      subjects on the same scenarios. SETTING: A university for older persons in
      Sichuan and the 4th Hospital of Sichuan University. SUBJECTS: Two hundred and one
      Sichuan Chinese (mean age: 63.3 years) comprising of healthy (31.8%) and disabled
      individuals with stroke, fracture, cancer or other chronic conditions (69.2%)
      were recruited in the study. RESULTS: Overall ratings for health scenarios were
      found to be highly correlated between Sichuan Chinese and UK subjects (r = 0.85;
      P < 0.0005), and between Sichuan and HK Chinese subjects (r = 0.98; P < 0.0005),
      with the exception of scenario J. Interesting differences in valuation were also
      observed between Sichuan subgroups in three scenarios. Self-perceived health
      status of the Sichuan Chinese can be accurately reflected by the severity of
      their handicap as measured by the London Handicap Scale LHS (r = -0.39, P =
      0.000). For Sichuan Chinese, the economic domain of handicap was rated with
      poorer scores compared with the other domains. CONCLUSION: The international
      notion of handicap, or limitation in participation, applies across different
      cultures and is also valid in mainland Chinese. UK, HK, and Sichuan subjects
      share similar perception on selected handicap scenarios. The London Handicap
      Scale is useful for health evaluation and outcome assessment for elderly of
      different cultures.

PMID- 17537748
TI  - Brain tumours and exposure to pesticides: a case-control study in southwestern
      France.
AB  - BACKGROUND: Brain tumours are often disabling and rapidly lethal; their aetiology
      is largely unknown. Among potential risk factors, pesticides are suspected.
      OBJECTIVE: To examine the relationship between exposure to pesticides and brain
      tumours in adults in a population-based case-control study in southwestern
      France. METHODS: Between May 1999 and April 2001, 221 incident cases of brain
      tumours and 442 individually matched controls selected from the general
      population were enrolled. Histories of occupational and environmental exposures,
      medical and lifestyle information were collected. A cumulative index of
      occupational exposure to pesticides was created, based on expert review of
      lifelong jobs and tasks. Separate analyses were performed for gliomas and
      meningiomas. RESULTS: A non-statistically significant increase in risk was found
      for brain tumours when all types of occupational exposure to pesticides were
      considered (OR = 1.29, 95% CI 0.87 to 1.91) and slightly higher but still non
      statistically significant when gliomas were considered separately (OR = 1.47, 95%
      CI 0.81 to 2.66). In the highest quartile of the cumulative index, a significant
      association was found for brain tumours (OR = 2.16, 95% CI 1.10 to 4.23) and for
      gliomas (OR = 3.21, 95% CI 1.13 to 9.11), but not for meningiomas. A significant
      increase in risk was also seen for the treatment of home plants (OR = 2.24, 95%
      CI 1.16 to 4.30) owing to environmental exposure to pesticides. CONCLUSIONS:
      These data suggest that a high level of occupational exposure to pesticides might
      be associated with an excess risk of brain tumours, and especially of gliomas.

PMID- 17537749
TI  - Short oligonucleotide probes containing G-stacks display abnormal binding
      affinity on Affymetrix microarrays.
AB  - MOTIVATION: In microarray experiments, probe design is critical to the specific
      and accurate measurement of target concentrations. Current designs select
      suitable probes through in silico scanning of transcriptome/genome based on first
      principles. However, due to lack of tools, the observed microarray data have not
      been used to assess the performance of individual probes to provide feedback to
      improve future designs. RESULT: In this study, we describe a probe performance
      assessment method based on the concordance of the observed signals from probes
      that share common targets. Using this method, we found that probes containing
      multiple guanines in a row (G-stacks) have abnormal binding behavior compared
      with other probes, both in gene expression assays and genotyping assays using
      Affymetrix microarrays. These probes are less likely to covary with other probes
      that interrogate the same genes. Moreover, we found that these probes are much
      more likely to produce outliers when fitting the observed signals according to
      the positional dependent nearest neighbor model, which gives reasonable estimates
      of binding affinity for most other probes. These results suggest that probes
      containing G-stacks tend to have increased cross hybridization signals and
      reduced target-specific hybridization signals, presumably due to multiplex
      binding forming G-quartet structures. Our findings are expected to be useful in
      microarray design and data analysis.

PMID- 17537750
TI  - StrBioLib: a Java library for development of custom computational structural
      biology applications.
AB  - SUMMARY: StrBioLib is a library of Java classes useful for developing software
      for computational structural biology research. StrBioLib contains classes to
      represent and manipulate protein structures, biopolymer sequences, sets of
      biopolymer sequences, and alignments between biopolymers based on either sequence
      or structure. Interfaces are provided to interact with commonly used
      bioinformatics applications, including (psi)-blast, modeller, muscle and Primer3,
      and tools are provided to read and write many file formats used to represent
      bioinformatic data. The library includes a general-purpose neural network object
      with multiple training algorithms, the Hooke and Jeeves non-linear optimization
      algorithm, and tools for efficient C-style string parsing and formatting.
      StrBioLib is the basis for the Pred2ary secondary structure prediction program,
      is used to build the astral compendium for sequence and structure analysis, and
      has been extensively tested through use in many smaller projects. Examples and
      documentation are available at the site below. AVAILABILITY: StrBioLib may be
      obtained under the terms of the GNU LGPL license from
      http://strbio.sourceforge.net/

PMID- 17537751
TI  - Clustering microarray-derived gene lists through implicit literature
      relationships.
AB  - MOTIVATION: Microarrays rapidly generate large quantities of gene expression
      information, but interpreting such data within a biological context is still
      relatively complex and laborious. New methods that can identify functionally
      related genes via shared literature concepts will be useful in addressing these
      needs. RESULTS: We have developed a novel method that uses implicit literature
      relationships (concepts related via shared, intermediate concepts) to cluster
      related genes. Genes are evaluated for implicit connections within a network of
      biomedical objects (other genes, ontological concepts and diseases) that are
      connected via their co-occurrences in Medline titles and/or abstracts. On the
      basis of these implicit relationships, individual gene pairs are scored using a
      probability-based algorithm. Scores are generated for all pairwise combinations
      of genes, which are then clustered based on the scores. We applied this method to
      a test set composed of nine functional groups with known relationships. The
      method scored highly for all nine groups and significantly better than a
      benchmark co-occurrence-based method for six groups. We then applied this method
      to gene sets specific to two previously defined breast tumor subtypes. Analysis
      of the results recapitulated known biological relationships and identified novel
      pathway relationships unique to each tumor subtype. We demonstrate that this
      method provides a valuable new means of identifying and visualizing significantly
      related genes within gene lists via their implicit relationships in the
      literature.

PMID- 17537752
TI  - Computational methods for diffusion-influenced biochemical reactions.
AB  - MOTIVATION: We compare stochastic computational methods accounting for space and
      discrete nature of reactants in biochemical systems. Implementations based on
      Brownian dynamics (BD) and the reaction-diffusion master equation are applied to
      a simplified gene expression model and to a signal transduction pathway in
      Escherichia coli. RESULTS: In the regime where the number of molecules is small
      and reactions are diffusion-limited predicted fluctuations in the product number
      vary between the methods, while the average is the same. Computational approaches
      at the level of the reaction-diffusion master equation compute the same
      fluctuations as the reference result obtained from the particle-based method if
      the size of the sub-volumes is comparable to the diameter of reactants. Using
      numerical simulations of reversible binding of a pair of molecules we argue that
      the disagreement in predicted fluctuations is due to different modeling of inter
      arrival times between reaction events. Simulations for a more complex biological
      study show that the different approaches lead to different results due to
      modeling issues. Finally, we present the physical assumptions behind the
      mesoscopic models for the reaction-diffusion systems. AVAILABILITY: Input files
      for the simulations and the source code of GMP can be found under the following
      address: http://www.cwi.nl/projects/sic/bioinformatics2007/

PMID- 17537753
TI  - Exploring sequence-structure relationships in the tyrosine kinome space:
      functional classification of the binding specificity mechanisms for cancer
      therapeutics.
AB  - MOTIVATION: Evolutionary and structural conservation patterns shared by more than
      500 of identified protein kinases have led to complex sequence-structure
      relationships of cross-reactivity for kinase inhibitors. Understanding the
      molecular basis of binding specificity for protein kinases family, which is the
      central problem in discovery of cancer therapeutics, remains challenging as the
      inhibitor selectivity is not readily interpreted from chemical proteomics
      studies, neither it is easily discernable directly from sequence or structure
      information. We present an integrated view of sequence-structure-binding
      relationships in the tyrosine kinome space in which evolutionary analysis of the
      kinases binding sites is combined with computational proteomics profiling of the
      inhibitor-protein interactions. This approach provides a functional
      classification of the binding specificity mechanisms for cancer agents targeting
      protein tyrosine kinases. RESULTS: The proposed functional classification of the
      kinase binding specificities explores mechanisms in which structural plasticity
      of the tyrosine kinases and sequence variation of the binding-site residues are
      linked with conformational preferences of the inhibitors in achieving effective
      drug binding. The molecular basis of binding specificity for tyrosine kinases may
      be largely driven by conformational adaptability of the inhibitors to an ensemble
      of structurally different conformational states of the enzyme, rather than being
      determined by their phylogenetic proximity in the kinome space or differences in
      the interactions with the variable binding-site residues. This approach provides
      a fruitful functional linkage between structural bioinformatics analysis and
      disease by unraveling the molecular basis of kinase selectivity for the prominent
      kinase drugs (Imatinib, Dasatinib and Erlotinib) which is consistent with
      structural and proteomics experiments.

PMID- 17537754
TI  - Mining co-regulated gene profiles for the detection of functional associations in
      gene expression data.
AB  - MOTIVATION: Association pattern discovery (APD) methods have been successfully
      applied to gene expression data. They find groups of co-regulated genes in which
      the genes are either up- or down-regulated throughout the identified conditions.
      These methods, however, fail to identify similarly expressed genes whose
      expressions change between up- and down-regulation from one condition to another.
      In order to discover these hidden patterns, we propose the concept of mining co
      regulated gene profiles. Co-regulated gene profiles contain two gene sets such
      that genes within the same set behave identically (up or down) while genes from
      different sets display contrary behavior. To reduce and group the large number of
      similar resulting patterns, we propose a new similarity measure that can be
      applied together with hierarchical clustering methods. RESULTS: We tested our
      proposed method on two well-known yeast microarray data sets. Our implementation
      mined the data effectively and discovered patterns of co-regulated genes that are
      hidden to traditional APD methods. The high content of biologically relevant
      information in these patterns is demonstrated by the significant enrichment of co
      regulated genes with similar functions. Our experimental results show that the
      Mining Attribute Profile (MAP) method is an efficient tool for the analysis of
      gene expression data and competitive with bi-clustering techniques.

PMID- 17537755
TI  - PALMA: mRNA to genome alignments using large margin algorithms.
AB  - MOTIVATION: Despite many years of research on how to properly align sequences in
      the presence of sequencing errors, alternative splicing and micro-exons, the
      correct alignment of mRNA sequences to genomic DNA is still a challenging task.
      RESULTS: We present a novel approach based on large margin learning that combines
      accurate splice site predictions with common sequence alignment techniques. By
      solving a convex optimization problem, our algorithm-called PALMA-tunes the
      parameters of the model such that true alignments score higher than other
      alignments. We study the accuracy of alignments of mRNAs containing artificially
      generated micro-exons to genomic DNA. In a carefully designed experiment, we show
      that our algorithm accurately identifies the intron boundaries as well as
      boundaries of the optimal local alignment. It outperforms all other methods: for
      5702 artificially shortened EST sequences from Caenorhabditis elegans and human,
      it correctly identifies the intron boundaries in all except two cases. The best
      other method is a recently proposed method called exalin which misaligns 37 of
      the sequences. Our method also demonstrates robustness to mutations, insertions
      and deletions, retaining accuracy even at high noise levels. AVAILABILITY:
      Datasets for training, evaluation and testing, additional results and a stand
      alone alignment tool implemented in C++ and python are available at
      http://www.fml.mpg.de/raetsch/projects/palma

PMID- 17537756
TI  - RNA Sampler: a new sampling based algorithm for common RNA secondary structure
      prediction and structural alignment.
AB  - MOTIVATION: Non-coding RNA genes and RNA structural regulatory motifs play
      important roles in gene regulation and other cellular functions. They are often
      characterized by specific secondary structures that are critical to their
      functions and are often conserved in phylogenetically or functionally related
      sequences. Predicting common RNA secondary structures in multiple unaligned
      sequences remains a challenge in bioinformatics research. METHODS AND RESULTS: We
      present a new sampling based algorithm to predict common RNA secondary structures
      in multiple unaligned sequences. Our algorithm finds the common structure between
      two sequences by probabilistically sampling aligned stems based on stem
      conservation calculated from intrasequence base pairing probabilities and
      intersequence base alignment probabilities. It iteratively updates these
      probabilities based on sampled structures and subsequently recalculates stem
      conservation using the updated probabilities. The iterative process terminates
      upon convergence of the sampled structures. We extend the algorithm to multiple
      sequences by a consistency-based method, which iteratively incorporates and
      reinforces consistent structure information from pairwise comparisons into
      consensus structures. The algorithm has no limitation on predicting pseudoknots.
      In extensive testing on real sequence data, our algorithm outperformed other
      leading RNA structure prediction methods in both sensitivity and specificity with
      a reasonably fast speed. It also generated better structural alignments than
      other programs in sequences of a wide range of identities, which more accurately
      represent the RNA secondary structure conservations. AVAILABILITY: The algorithm
      is implemented in a C program, RNA Sampler, which is available at
      http://ural.wustl.edu/software.html

PMID- 17537757
TI  - Assessing breast tissue density by transillumination breast spectroscopy (TIBS):
      an intermediate indicator of cancer risk.
AB  - Risk assessment by parenchymal density pattern, a strong physical indicator of
      future breast cancer risk, is available with the onset of mammographic screening
      programmes. However, due to the use of ionizing radiation, mammography is not
      recommended for use in younger women, thereby rendering risk assessment
      unattainable at an earlier age. Visible and near infrared light was used on 292
      women with radiologically normal mammograms to determine whether
      transillumination breast spectroscopy (TIBS) can identify women with a high
      parenchymal density pattern as an intermediate indicator of breast cancer risk.
      Principal component analysis (PCA) was used to reduce the spectral data and
      generate density scores for each woman. To assess the accuracy of TIBS, logistic
      regression was used to calculate crude and adjusted odds ratios (OR) and 95%
      confidence intervals (CI) for each score. Receiver operator characteristic (ROC)
      curves and area under the curve (AUC) were also calculated for the crude and
      adjusted logistic models. Optical information relating to tissue chromophores,
      such as water, lipid and haemoglobin content, was sufficient to identify women
      with high parenchymal density. The resulting AUC for the final and most
      parsimonious multivariate logistic model was 0.922 (95% CI 0.878-0.967). TIBS
      provides information correlating to high parenchymal density and is a promising
      tool for risk assessment, particularly for younger women.

PMID- 17537758
TI  - FDG-PET/CT in restaging of patients with recurrent breast cancer: possible impact
      on staging and therapy.
AB  - We aimed to compare the value of combined positron emission tomography (PET)/CT,
      PET+CT (viewed side by side), CT alone and PET alone concerning the rTNM stage
      and influence on therapy in patients with recurrent breast cancer. 44 patients
      with suspicion of recurrent breast cancer underwent whole-body [18F]-2-fluoro-2
      deoxy-d-glucose (FDG)-PET/CT. Images of combined PET/CT, PET+CT, PET alone and CT
      alone were evaluated by four blinded reader teams. Diagnostic accuracies and
      influence on therapy were compared. Histology and a mean clinical follow up of
      456 days served as the standard of reference. Differences between the staging
      procedures were tested for statistical significance by McNemar's test. Overall
      TNM tumour stage was correctly determined in 40/44 patients with PET/CT, in 38/44
      with PET+CT, in 36/44 with PET alone and in 36/44 patients with CT alone. No
      statistically significant difference was detected between all tested imaging
      modalities. PET/CT changed the therapy in two patients compared with PET+CT, in
      four patients compared with PET alone and in five patients compared with CT
      alone. Combined PET/CT appeared to be more accurate in assessing the rTNM and
      showed a moderate impact on therapy over PET and CT. Minor improvements were
      noted when compared with PET+CT. Experienced readers might therefore be able to
      provide accurate staging results for further therapy from separately acquired
      studies.

PMID- 17537759
TI  - Infant feeding in the second 6 months of life related to iron status: an
      observational study.
AB  - OBJECTIVE: To investigate the relationship between iron status in infancy and
      type of milk and weaning solids consumed. DESIGN: An observational cohort study.
      SETTING: 928 term infants from the Avon Longitudinal Study of Parents and
      Children in 1993-94. METHODS: Haemoglobin and ferritin concentrations at 8 and 12
      months were assessed in relation to type and quantity of milk intake at 8 months.
      RESULTS: By WHO criteria, 22.7% of the infants were anaemic at 8 months and 18.1%
      at 12 months. More breast--than formula-fed infants were anaemic at 8 and 12
      months. Cows' milk as the main drink was associated with increased anaemia at 12
      months and low ferritin at 8 and 12 months. No association was found between any
      nutrients and haemoglobin concentrations. Protein and non-haem iron intakes were
      positively associated with ferritin concentrations and calcium intake negatively.
      This effect was more marked in infants being fed cows' milk. More than 25% of
      infants in the breast milk and cows' milk groups and 41% of infants having >6
      breast feeds per day had iron intakes below the lower reference nutrient intake.
      Feeding cows' milk or formula above 600 ml or >6 breast feeds per day was
      associated with lower intakes of solids. CONCLUSIONS: Both breast and cows' milk
      feeding were associated with higher levels of anaemia. Satisfactory iron intake
      from solids in later infancy is more likely if formula intake is <600 ml per day
      and breast feeds are limited to <6 feeds per day. Cows' milk should be strongly
      discouraged as a main drink before 12 months.

PMID- 17537760
TI  - Neonatal vitamin K prophylaxis in Great Britain and Ireland: the impact of
      perceived risk and product licensing on effectiveness.
AB  - OBJECTIVE: To determine current use of vitamin K (VK) prophylaxis in newborns and
      review the efficacy and effectiveness of regimens used. DESIGN: Efficacy and
      effectiveness calculated using current practice details, data from Southern
      Ireland and two previous surveys, together with contemporaneous studies of
      vitamin K deficiency bleeding (VKDB). SETTING: Current survey: United Kingdom
      (Great Britain and Northern Ireland). Efficacy and effectiveness tables: United
      Kingdom and Southern Ireland. MAIN OUTCOME MEASURES: Current VK prophylaxis
      following uncomplicated term deliveries. Relative risk of VKDB calculated for the
      VK actually received and for "intention to treat". RESULTS: Questionnaire
      response rate 95% (n = 243), all recommending VK prophylaxis. No association
      between unit size and route of administration. For uncomplicated term deliveries,
      60% recommended intramuscular (IM) prophylaxis, 24% oral and 16% offered both
      routes without bias. All units offering IM gave a single dose, mostly 1 mg
      Konakion Neonatal. Oral regimens showed more variation: two thirds gave 2 mg
      (range 0.5-2 mg), the number of doses ranged from 1 to 11 and many used
      preparations off-licence or the unlicensed Orakay. IM prophylaxis, if given,
      provided the best protection (most efficacious) against VKDB. However, on an
      intention-to-treat basis (effectiveness), there is no statistically significant
      difference between the risks of VKDB after intended IM VK and after oral
      prophylaxis intended to continue beyond a week. CONCLUSIONS: Although the
      principles of VK prophylaxis is now accepted by all, there is no uniformity in
      practice. Omission of prophylaxis appears to be a greater problem for IM than for
      multi-dose oral prophylaxis, affecting overall effectiveness.

PMID- 17537761
TI  - Vitamin K deficiency bleeding in Great Britain and Ireland: British Paediatric
      Surveillance Unit Surveys, 1993 94 and 2001-02.
AB  - OBJECTIVE: To conduct and report monitoring of vitamin K deficiency bleeding
      (VKDB) in Great Britain and Ireland following the 1988-90 survey (VKDB-90).
      DESIGN: Two 2-year surveys conducted during 1993-4 (VKDB-94) and 2001-02 (VKDB
      02). SETTING: Data collected from all consultant paediatricians in Great Britain
      and Ireland. PATIENTS: All infants presenting with bleeding resulting from
      vitamin K (VK) deficiency. MAIN OUTCOME MEASURES: Incidence of VKDB, related
      mortality/morbidity and VK prophylaxis recommended/received, noting predisposing
      features. RESULTS: Compared with previous studies, VKDB-02 found fewer cases of
      VKDB (RR: 0.27 (95% CI: 0.12 to 0.59), p<0.001) with no deaths, no long-term
      morbidity and reduced incidence among those receiving any oral dosing (RR: 0.24
      (95% CI: 0.06 to 1.01), p<0.059). Breast-fed infants accounted for the vast
      majority of cases. The number receiving no prophylaxis fell consecutively over
      time: 20 of 27 in VKDB-90, 10 of 32 in VKDB-94 and 4 (because of parental
      refusal) of 7 in VKDB-02. Seven received one oral dose of VK in VKDB-90, 16 in
      VKDB-94 and none in VKDB-02. Underlying liver disease was found in six cases in
      VKDB-90, 12 in VKDB-94 and one in VKDB-02. CONCLUSIONS: In the most recent
      survey, the incidence of VKDB was about one third that in the two earlier
      studies. Late onset VKDB remains virtually confined to breast-fed infants who
      have received either no VK or just one oral dose. The effectiveness of oral
      prophylaxis regimens has improved over the last 15 years, but parental refusal of
      prophylaxis has become more problematic.

PMID- 17537762
TI  - Natural anticoagulants limit lipopolysaccharide-induced pulmonary coagulation but
      not inflammation.
AB  - Pulmonary coagulopathy and hyperinflammation may contribute to an adverse outcome
      in sepsis. The present study determines the effects of natural inhibitors of
      coagulation on bronchoalveolar haemostasis and inflammation in a rat model of
      endotoxaemia. Male Sprague-Dawley rats were randomised to treatment with normal
      saline, recombinant human activated protein C (APC), plasma-derived antithrombin
      (AT), recombinant human tissue factor pathway inhibitor (TFPI), heparin or
      recombinant tissue plasminogen activator (tPA). Rats were intravenously injected
      with lipopolysaccharide (LPS), which induced a systemic inflammatory response and
      pulmonary inflammation. Blood and bronchoalveolar lavage were obtained at 4 and
      16 h after LPS injection, and markers of coagulation and inflammation were
      measured. LPS injection caused an increase in the levels of thrombin-AT
      complexes, whereas plasminogen activator activity was attenuated, both
      systemically and within the bronchoalveolar compartment. Administration of APC,
      AT and TFPI significantly limited LPS-induced generation of thrombin-AT complexes
      in the lungs, and tPA stimulated pulmonary fibrinolytic activity. However, none
      of the agents had significant effects on the production of pulmonary cytokines,
      chemokines, neutrophil influx and myeloperoxidase activity. Natural inhibitors of
      coagulation prevent bronchoalveolar activation of coagulation, but do not induce
      major alterations of the pulmonary inflammatory response in rat endotoxaemia.

PMID- 17537763
TI  - Severe exacerbations predict excess lung function decline in asthma.
AB  - Severe asthma exacerbations are periods of intense airway inflammation that have
      been hypothesised to contribute to structural changes in the airways. If so,
      accelerated lung function decline over time should be more prevalent in adult
      patients with asthma who have frequent exacerbations than those without, but to
      date this has not been demonstrated. A cohort study was performed in order to
      investigate the effect of severe exacerbations on the progression of airway
      obstruction in 93 nonsmoking asthmatics with moderate-to-severe disease prior to
      treatment with inhaled corticosteroids. Subjects were followed for > or =5 yrs
      (median follow-up 11 yrs). In total, 56 (60.2%) subjects experienced at least one
      severe exacerbation (median rate 0.10.yr(-1)). Oral corticosteroid use and more
      severe airway obstruction at baseline were associated with a higher exacerbation
      rate. Independent of these variables, asthma patients with frequent exacerbations
      had a significantly larger annual decline in forced expiratory volume in one
      second (FEV(1); median difference (95% confidence interval) 16.9 (1.5-32.2)
      mL.yr(-1)). Exacerbation rate significantly predicted an excess decline in
      FEV(1), such that one severe exacerbation per year was associated with a 30.2 mL
      greater annual decline in FEV(1). These data support the hypothesis that
      exacerbations, indicating intermittent periods of worsening airway inflammation,
      are associated with excess lung function decline in asthma.

PMID- 17537764
TI  - Daily versus weekly azithromycin in cystic fibrosis patients.
AB  - Four randomised, placebo-controlled trials have previously documented the
      clinical benefits of azithromycin (AZM) in cystic fibrosis (CF) patients. The
      present study examined whether the beneficial effect of AZM is equivalent when
      administered daily or weekly. A double-blind, randomised study was carried out in
      208 CF patients aged 6-58 yrs who were assigned to AZM either 250 mg daily (n =
      103) or 1,200 mg weekly (n = 105) for 6 months, with assessments at baseline and
      at 1, 3, 6 and 7 months. Patients were taken from five adult and children CF
      centres in South-east Queensland, Australia. Equivalence was demonstrated between
      the two groups (daily versus weekly) with respect to improvements in lung
      function (forced expiratory volume in one second and forced vital capacity), C
      reactive protein, days spent in hospital, admission rates and nutrition (body
      mass index, z-scores) using 95% confidence intervals with a tolerance interval of
      +/-10%. In patients aged <18 yrs the daily group had significantly better
      improvements in z-scores for height and weight after 6 months. In children, a
      nutritional advantage for daily administration was found. Gastro-intestinal
      adverse effects were more common with weekly therapy. Apart from these findings,
      daily and weekly administered azithromycin demonstrated similar outcomes for
      cystic fibrosis patients.

PMID- 17537765
TI  - Suppression of endotoxin-induced inflammation by taxol.
AB  - The pathogenesis of acute lung injury includes transendothelial diapedesis of
      leukocytes into lung tissues and disruption of endothelial/epithelial barriers
      leading to protein-rich oedema. In vitro studies show that the microtubule
      network plays a role in the regulation of endothelial permeability as well as in
      neutrophil locomotion. It was hypothesised that the microtubule-stabilising
      agent, taxol, might attenuate inflammation and vascular leak associated with
      acute lung injury in vivo. The effect of intravenously delivered taxol was
      assessed using a model of murine lung injury induced by intratracheal
      lipopolysaccharide (LPS) administration. Parameters of lung injury and
      inflammation were assessed 18 h after treatment. Intravenously delivered taxol
      significantly reduced inflammatory histological changes in lung parenchyma and
      parameters of LPS-induced inflammation: infiltration of proteins and inflammatory
      cells into bronchoalveolar lavage fluid, lung myeloperoxidase activity, and
      extravasation of Evans blue-labelled albumin into lung tissue. Taxol alone (in
      the absence of LPS) had no appreciable effect on these parameters. In addition to
      lung proteins, intravenous taxol reduced accumulation of leukocytes in ascitic
      fluid in a model of LPS-induced peritonitis. Taken together, the present data
      demonstrate that microtubule stabilisation with taxol systemically attenuates
      lipopolysaccharide-induced inflammation and vascular leak.

PMID- 17537766
TI  - First months of employment and new onset of rhinitis in adolescents.
AB  - The aim of the present study was to investigate the incidence of rhinitis in
      adolescents, taking into account the duration and type of employment in holiday
      and vocational jobs, and to study latency until development of symptoms.
      Participants of the International Study of Asthma and Allergies in Childhood
      (ISAAC)-II study in Munich and Dresden (Germany), who were enrolled in 1995, were
      re-contacted by a postal questionnaire in 2002 (aged 16-18 yrs). The
      questionnaire focused on allergic rhinitis, type and duration of all jobs, and
      potential confounders. All jobs held for >/=8 h.week(-1) and >/=1 month were
      coded and occupational exposure was assigned by a job-exposure matrix. Out of the
      3,785 participants, 964 reported an employment history. The median (25th-75th
      percentile) duration of employment was 10 (1-16) months. After adjusting for
      potential confounders, those working in high-risk occupations (odds ratio (OR)
      1.4, 95% confidence interval (CI) 1.0-2.1) had an increased risk for new onset of
      rhinitis, especially those exposed to low molecular weight agents (OR 1.8, 95% CI
      1.1-2.8). The incidence of rhinitis was highest among those currently employed in
      a high-risk job for <10 months. Teenagers who start working in high-risk
      occupations have a higher incidence of rhinitis compared with those not working.
      This increased risk might occur early on during employment.

PMID- 17537767
TI  - Influenza vaccination and mortality: prospective cohort study of the elderly in a
      large geographical area.
AB  - The 50% reduced overall mortality previously associated with influenza
      vaccination among the elderly was based on studies neither fully taking into
      account systematic differences between individuals who accept or decline
      vaccination nor encompassing the entire general population. A population-based
      prospective cohort study was performed in Stockholm County (Sweden), including
      all persons aged > or =65 yrs (n = approximately 260,000), over three influenza
      seasons: 1998/1999, 1999/2000 and 2000/2001. The relative risks of mortality
      among vaccinated versus unvaccinated individuals were estimated using Cox's
      proportional hazards regression adjusted for, and stratified by, demographic
      factors and comorbid conditions during the three seasons and the respective
      following off-seasons. Influenza vaccination was associated with an unadjusted
      reduction in all-cause mortality during the three seasons of 50, 46 and 42%,
      respectively, which decreased to 14, 19 and 1%, respectively, following
      adjustment for confounders and differences in mortality between vaccinated and
      unvaccinated individuals following the influenza season. The numbers needed to
      treat to prevent one death, during the three seasons, were 297, 158 and 743,
      respectively. Vaccination remains the most important measure for prevention of
      influenza complications in elderly people, although the effectiveness in reducing
      all-cause mortality in elderly persons is lower than previously thought.

PMID- 17537768
TI  - New recommendations for duration of respiratory isolation based on time to detect
      Mycobacterium tuberculosis in liquid culture.
AB  - It was hypothesised that the time to detect Mycobacterium tuberculosis in liquid
      culture of sputum from patients with pulmonary tuberculosis may be a better
      indicator for the duration of respiratory isolation than sputum smear status. Pre
      treatment and during-treatment sputum acid-fast bacilli (AFB) smear and culture
      results were reviewed in 284 patients with pulmonary tuberculosis. The time to
      detect M. tuberculosis in liquid culture (TTD-TB) was the number of days from
      inoculation of the Mycobacterial Growth Indicator Tube to culture detection and
      visualisation of AFB. The median (interquartile range) TTD-TB for smear group 0
      (no bacilli seen) was 14 (12-20) days. This value was used as the standard at
      which release from isolation could be permitted. In smear group 4 (>9 AFB per
      high-power field (hpf) in sputum specimens before treatment) patients, the TTD-TB
      exceeded 14 days after a median of 25 days of treatment. The current authors
      recommend that patients in smear groups 1 and 2 (1-9 AFB per 100 hpf and 1-9 AFB
      per 10 hpf in sputum specimens before treatment, respectively) receive treatment
      in respiratory isolation for 7 days, provided the risk of drug resistance is low.
      Smear group 3 (1-9 AFB per hpf) and 4 patients should receive treatment in
      respiratory isolation for 14 and 25 days, respectively. These criteria would have
      reduced the duration of respiratory isolation by 1,516 days in the 143 study
      participants with sputum smear-positive pulmonary tuberculosis. Provided clinical
      and radiographical criteria are satisfactory, use of the time to detect
      Mycobacterium tuberculosis in liquid culture could enable the duration of
      respiratory isolation to be predicted from the pre-treatment sputum smear grade.
      The recommendations enable isolation to end well before sputum becomes smear
      negative, with considerable benefits to patients and healthcare providers.

PMID- 17537769
TI  - Macrophage expression of interleukin-10 is a prognostic factor in nonsmall cell
      lung cancer.
AB  - Interleukin (IL)-10 is expressed in many solid tumours and plays an ambiguous
      role in controlling cancer growth and metastasis. In order to determine whether
      IL-10 is involved in tumour progression and prognosis in nonsmall cell lung
      cancer (NSCLC), IL-10 expression in tumour cells and tumour-associated
      macrophages (TAMs) and its associations, if any, with clinicopathological
      features were investigated. Paraffin-embedded sections of surgical specimens
      obtained from 50 patients who had undergone surgery for NSCLC were immunostained
      with an antibody directed against IL-10. TAMs and tumour cells positive for IL-10
      were subsequently quantified. IL-10-positive TAM percentage was higher in
      patients with stage II, III and IV NSCLC, and in those with lymph node metastases
      compared with patients with stage I NSCLC. High IL-10 expression by TAMs was a
      significant independent predictor of advanced tumour stage, and thus was
      associated with worse overall survival. Conversely, IL-10 expression by tumour
      cells did not differ between stages II, III and IV and stage I NSCLC. In
      conclusion, interleukin-10 expression by tumour-associated macrophages, but not
      by tumour cells, may play a role in the progression and prognosis of nonsmall
      cell lung cancer. These results may be useful in the development of novel
      approaches for anticancer treatments.

PMID- 17537770
TI  - Long-term asthma treatment guided by airway hyperresponsiveness in children: a
      randomised controlled trial.
AB  - Management plans for childhood asthma show limited success in optimising asthma
      control. The aim of the present study was to assess whether a treatment strategy
      guided by airway hyperresponsiveness (AHR) increased the number of symptom-free
      days and improved lung function in asthmatic children, compared with a symptom
      driven reference strategy. In a multicentre, double-blind, parallel-group,
      randomised, 2-yr intervention trial, 210 children (aged 6-16 yrs) with moderate
      atopic asthma, selected on the basis of symptom scores and/or the presence of
      AHR, were studied. At 3-monthly visits, symptom scores, forced expiratory volume
      in one second (FEV(1)) and methacholine challenge results were obtained, and
      medication (five levels of fluticasone with or without salmeterol) adjusted
      according to algorithms based on symptom score (reference strategy, n = 104) or
      AHR and symptom score (AHR strategy, n = 102). After 2 yrs, no difference was
      found in the percentage of symptom-free days between treatment strategies. Pre
      bronchodilator FEV(1) was higher in the AHR strategy (2.3% predicted). This was
      entirely explained by a gradual worsening of FEV(1) in a subgroup of 91
      hyperresponsive children enrolled with low symptom scores (final difference
      between study arms was 6%). Asthma treatment guided by airway hyperresponsiveness
      showed no benefits in terms of number of symptom-free days, but produced a better
      outcome in terms of pre-bronchodilator forced expiratory volume in one second in
      allergic asthmatic children, especially those characterised by low symptom scores
      despite airway hyperresponsiveness.

PMID- 17537771
TI  - Nocturnal melatonin plasma levels in patients with OSAS: the effect of CPAP.
AB  - Melatonin is a pineal hormone that regulates the human cycle of sleep and
      wakefulness. Plasma melatonin levels were investigated in patients with
      obstructive sleep apnoea syndrome (OSAS). In total, 20 patients with OSAS and 11
      healthy controls were studied. OSAS patients were tested twice: on the night of
      diagnostic polysomnography and the night of continuous positive airway pressure
      (CPAP) titration. Controls were tested on one occasion. Plasma melatonin levels
      were determined at 23:00 h (light period), at 02:00 h (dark period) and at 06:00
      h (light period) in patients and control subjects using the radioimmunoassay
      method. The control subjects showed a nocturnal melatonin peak value at 02:00 h
      (70.6+/-14 pg.mL(-1)). However, this nocturnal melatonin peak was absent in the
      OSAS patients. The highest melatonin value was found in OSAS patients on the
      night of diagnosis, at 06:00 h (49.3+/-36.8 pg.mL(-1)). It was found that the
      melatonin level in OSAS patients at 06:00 h was significantly lower in the night
      of titration (35.6+/-37.9 pg.mL(-1)) than in the diagnosis night. However, the
      melatonin levels at either 23:00 h or 02:00 h in OSAS patients did not differ
      significantly when comparing levels in the night of diagnostic polysomnography
      (23:00 h: 31.6+/-29.8 pg.mL(-1); 02:00 h: 47.4+/-33.8 pg.mL(-1)) with levels in
      the night of CPAP titration (23:00 h: 20.2+/-10.3 pg.mL(-1); 02:00 h: 37.7+/-27.5
      pg.mL(-1)). Patients with obstructive sleep apnoea syndrome have an abnormal
      melatonin secretion pattern. The absence of a nocturnal serum melatonin peak
      could be partially related to the difficulty that these patients have in
      achieving a normal sleep-wakefulness pattern.

PMID- 17537772
TI  - The need for macrolides in hospitalised community-acquired pneumonia: propensity
      analysis.
AB  - The present study compared beta-lactam macrolide ("combination") therapy versus
      beta-lactam alone ("monotherapy") for hospitalised community-acquired pneumonia,
      using propensity scores to adjust for the differences between patients. A
      prospective multinational observational study was carried out. Baseline patient
      and infection characteristics were used to develop a propensity score for
      combination therapy. Patients were matched by the propensity score (three decimal
      point precision) and compared with 30-day mortality and hospital stay. The
      propensity score was used as a covariate in a logistic model for mortality.
      Patients treated with monotherapy (n = 169) were older (mean+/-sd age 70.6+/-17.3
      versus 65.0+/-19.6 yrs), had a higher chronic diseases score and a different
      clinical presentation compared with patients treated with combination therapy (n
      = 282). Unadjusted mortality was significantly higher with monotherapy (37 (22%)
      out of 169 versus 21 (7%) out of 282). Only 27 patients in the monotherapy group
      could be matched to 27 patients in the combination group using the propensity
      score. The mortality in these groups was identical, with three (11%) demises
      each. The multivariable odds ratio for mortality associated with combination
      therapy, adjusted for the propensity score and the Pneumonia Severity Index, was
      0.69 (95% confidence interval 0.32-1.48). The benefit of combination therapy
      versus monotherapy cannot be reliably assessed in observational studies, since
      the propensity to prescribe these regimens differs markedly.

PMID- 17537773
TI  - Quantitative scoring of an interferon-gamma assay for differentiating active from
      latent tuberculosis.
AB  - The aim of this study was to assess the contribution of an interferon-gamma
      release assay (T-SPOT.TB) to the differentiation of active tuberculosis (TB) from
      latent TB infection by quantifying spot-forming units (sfu). The investigation
      was a prospective study of contacts exposed to a case of contagious TB and cases
      of HIV-negative culture-proven TB referred over a 16-month period. Tuberculin
      skin tests (TSTs) and T-SPOT.TB were performed in 310 contacts 8-12 weeks after
      exposure. In subjects with culture-proven TB, T-SPOT.TB was performed within 2
      weeks of initiation of treatment. The analysis included all contacts with a
      positive T-SPOT.TB result and all subjects with TB. TB contacts (n = 127) and
      cases (n = 58) were included. Mean+/-sd T-SPOT.TB results were 107+/-56 (range 1
      207) sfu for TB, 54+/-60 (7-239) sfu for contacts with positive T-SPOT.TB results
      and a TST induration diameter of >5 mm, and 19+/-27 (7-143) sfu for contacts with
      positive T-SPOT.TB results and a TST induration diameter of < or =5 mm. By
      receiver operating characteristic curve analysis, a threshold value of 49.5 sfu
      showed a sensitivity of 83% and specificity of 74% for distinguishing latent TB
      infection from TB. Although T-SPOT.TB results were significantly related to
      disease activity, the test cannot be recommended for the diagnosis of
      tuberculosis.

PMID- 17537774
TI  - Kinetics of in vitro bronchoconstriction in an elastolytic mouse model of
      emphysema.
AB  - Thin-slice videomicroscopy was used to examine the kinetics of constriction in
      small airways in situ. Balb/C mice inhaled elastase (0-20 IU), and were then left
      to recover for 14 days before euthanisation and lung removal. Cholinergic
      responsiveness was assessed in thin lung slices. Magnitude and velocity of
      narrowing in response to 10(-5) M acetylcholine (ACh), as well as the full
      concentration-response relationship for ACh (10(-8)-10(-5) M) were assessed. In
      vivo exposure to elastase was accompanied by statistically significantly
      decreased magnitudes and velocities of contraction, but no change in the ACh
      concentration-response relationship. Conversely, overnight, in vitro exposure of
      slices from control animals to elastase (2.5 microg.mL(-1)) resulted in increased
      magnitudes and velocities of airway narrowing, with impaired relaxation, as well
      as marked tearing of the airways from the surrounding parenchyma. These changes
      are characteristic of decreased tethering forces on the airway wall. Thus, the
      lung slice technique coupled with videomicroscopic analysis of airway contraction
      velocities provides a powerful tool to study airway-parenchymal interactions. The
      elastolytic model of emphysema, which manifests with airspace enlargement and
      loss of parenchymal attachments, is accompanied by decreased airway contraction
      kinetics. The mechanism(s) underlying this loss of function remain to be
      elucidated.

PMID- 17537775
TI  - Sepsis severity predicts outcome in community-acquired pneumococcal pneumonia.
AB  - Easily performed prognostic rules are helpful for guiding the intensity of
      monitoring and treatment of patients. The aim of the present study was to compare
      the predictive value of the sepsis score and the Confusion, Respiratory rate (>
      or =30 breaths.min(-1)), Blood pressure (systolic value <90 mmHg or diastolic
      value < or =60 mmHg) and age > or =65 yrs (CRB-65) score in 105 patients with
      community-acquired pneumococcal pneumonia. In addition, the influence of timing
      of the antimicrobial treatment on outcome was investigated. The sepsis and the
      CRB-65 scores were used to allocate patients to subgroups with low, intermediate
      and high risk. Comparable, highly predictive values for mortality were found for
      both scores (sepsis score versus CRB-65): 1) low-risk group, 0 versus 0%; 2)
      intermediate-risk group, 0 versus 8.6%; 3) high-risk group, 30.6 versus 40%, with
      an area under the curve of 0.867 versus 0.845. Patients with ambulatory
      antibiotic pre-treatment had less severe disease with a lower acute physiology
      score, lower white blood cell count and a faster decline of C-reactive protein
      levels. No pre-treated patient died. In summary, both scores performed equally
      well in predicting mortality. The prediction of survival in the intermediate-risk
      group might be more accurate with the sepsis score. Pre-hospital antibiotic
      treatment was associated with less severe disease.

PMID- 17537776
TI  - Respiratory symptoms, atopy and bronchial hyperreactivity in professional
      firefighters.
AB  - The aim of the present study was to assess respiratory health in professional
      firefighters. A total of 101 male professional firefighters from Basel,
      Switzerland, were included in the study. A control group consisting of 735 male
      subjects of the general population was composed of the Basel sample of the Swiss
      Study on Air Pollution and Lung Diseases in Adults. All subjects were
      administered a standardised questionnaire, spirometry, skin-prick tests and
      bronchial challenge testing to methacholine. Respiratory symptoms at work were
      more frequent in firefighters compared with the control group, including burning
      eyes (21 versus 3%), running nose (19 versus 2%), itchy throat (26 versus 3%),
      cough (28 versus 3%), dyspnoea (7 versus 2%) and headache (25 versus 3%),
      respectively. Atopy was present in 51% of firefighters compared with 32% in the
      control group. The odds ratio for hyperreactivity to methacholine was 2.24 (95%
      confidence interval 1.12-4.48) for firefighters compared with the control group.
      Firefighters reported more respiratory symptoms at work and suffered more often
      from atopy compared with the control group. Bronchial hyperreactivity was more
      pronounced in firefighters, but it was not related to acute exposure or duration
      of employment. It remains unclear whether these findings were present at
      recruitment or developed after joining the workforce.

PMID- 17537777
TI  - Cigarette smoke condensate inhibits ENaC alpha-subunit expression in lung
      epithelial cells.
AB  - Cigarette smoke has been associated with lung fluid accumulation and increased
      risk of acute respiratory distress syndrome. It was postulated that ENaC alpha
      subunit, which plays a critical role in lung fluid absorption, is affected by
      cigarette smoke. Cigarette smoke condensate (CSC) was used to treat a human lung
      epithelial cell line. ENaC alpha-subunit expression was measured using
      immunoblotting, quantitative PCR and promoter-reporter assays. The current
      authors found that CSC, without affecting cell survival, suppressed alpha-subunit
      expression at the transcriptional level in a dose- and time-dependent fashion.
      This suppression is neither related to nicotine nor due to an increase of
      hydrogen peroxide levels in CSC-treated cells. CSC also suppressed alpha-subunit
      core promoter activity. Dexamethasone, which activates the core promoter, was
      able to attenuate the inhibitory effect of CSC. However, in the presence of CSC,
      dexamethasone was unable to elicit a full-scale activation of alpha-subunit
      expression. This inhibition of dexamethasone was partially reversed by withdrawal
      of CSC. The present results demonstrate that cigarette smoke condensate inhibits
      ENaC alpha-subunit expression at the transcriptional level through its promoter.
      This inhibition could be reversed by dexamethasone. The results also suggest that
      higher doses of dexamethasone may be needed to activate alpha-subunit expression
      in smokers' lungs compared with nonsmokers' lungs, and that quitting smoking
      might improve the effectiveness of dexamethasone.

PMID- 17537778
TI  - Moraxella catarrhalis induces ERK- and NF-kappaB-dependent COX-2 and
      prostaglandin E2 in lung epithelium.
AB  - Moraxella catarrhalis is a major cause of infectious exacerbations of chronic
      obstructive lung disease. Cyclooxygenase (COX)-derived prostaglandins, such as
      prostaglandin E(2) (PGE(2)), are considered to be important regulators of lung
      function. The present authors tested the hypothesis that M. catarrhalis induces
      COX-2-dependent PGE(2) production in pulmonary epithelial cells. In the present
      study, the authors demonstrate that M. catarrhalis specifically induces COX-2
      expression and subsequent PGE(2) release in pulmonary epithelial cells.
      Furthermore, the prostanoid receptor subtypes EP2 and EP4 were also upregulated
      in these cells. The M. catarrhalis-specific ubiquitous cell surface protein A1
      was important for the induction of COX-2 and PGE(2). Moreover, M. catarrhalis
      induced COX-2 and PGE(2) expression was dependent on extracellular signal
      regulated kinase 1/2-driven activation of nuclear factor-kappaB, but not on the
      activation of p38 mitogen-activated protein kinase. In conclusion, the present
      data suggest that ubiquitous cell surface protein A1 of Moraxella catarrhalis,
      extracellular signal-regulated kinase 1/2 and nuclear factor-kappaB control
      cyclooxygenase-2 expression and subsequent prostaglandin E(2) release by lung
      epithelial cells. Moraxella catarrhalis-induced prostaglandin E(2) expression
      might counteract lung inflammation promoting colonisation of the respiratory
      tract in chronic obstructive pulmonary disease patients.

PMID- 17537780
TI  - Molecular evidence for the role of mycobacteria in sarcoidosis: a meta-analysis.
AB  - The aetiology of sarcoidosis is currently unknown. Due to the clinical and
      histological similarities between sarcoidosis and tuberculosis, the role of
      mycobacteria has been repeatedly investigated as an aetiological agent for
      sarcoidosis. The current meta-analysis aimed to evaluate the available molecular
      evidence on the possible role of mycobacteria in the development of sarcoidosis.
      The MEDLINE, EMBASE, CINAHL, DARE and CENTRAL databases were searched for
      relevant studies published from 1980 to 2006, and studies evaluating the presence
      of mycobacteria using molecular techniques in biological samples of patients with
      sarcoidosis were included in the current analysis. The 95% confidence intervals
      (CI) were calculated for the expected proportion (of individual studies); the
      data was then pooled to obtain a summary success rate with 95% CI. The odds ratio
      (95% CI) was also calculated in order to assess the presence of mycobacteria in
      samples of patients with sarcoidosis versus those from nonsarcoidosis control
      samples. The database search yielded 31 studies. All studies used polymerase
      chain reaction for nucleic acid amplification followed by identification of
      nucleic acid sequences specific for different types of mycobacteria. Overall, 231
      out of the 874 patients were positive for mycobacteria with a positive signal
      rate of 26.4 (23.6-29.5%), and the odds of finding mycobacteria in samples of
      patients with sarcoidosis versus controls were 9.67 (4.56-20.5%) using the random
      effects model and 19.49 (11.21-35.54%) using the exact method. There was
      methodological and statistical heterogeneity and evidence of publication bias.
      The results of the current study illustrate a demonstrable mycobacterial presence
      in sarcoidosis lesions suggesting an association between mycobacteria and some
      cases of sarcoidosis. To avoid methodological diversity, larger multicentre
      trials with a central laboratory for sample testing should be designed.

PMID- 17537779
TI  - Inhibition of allergen-induced airway remodelling by tiotropium and budesonide: a
      comparison.
AB  - Chronic inflammation in asthma and chronic obstructive pulmonary disease drives
      pathological structural remodelling of the airways. Using tiotropium bromide,
      acetylcholine was recently identified as playing a major regulatory role in
      airway smooth muscle remodelling in a guinea pig model of ongoing allergic
      asthma. The aim of the present study was to investigate other aspects of airway
      remodelling and to compare the effectiveness of tiotropium to the
      glucocorticosteroid budesonide. Ovalbumin-sensitised guinea pigs were challenged
      for 12 weeks with aerosolised ovalbumin. The ovalbumin induced airway smooth
      muscle thickening, hypercontractility of tracheal smooth muscle, increased
      pulmonary contractile protein (smooth-muscle myosin) abundance, mucous gland
      hypertrophy, an increase in mucin 5 subtypes A and C (MUC5AC)-positive goblet
      cell numbers and eosinophilia. It was reported previously that treatment with
      tiotropium inhibits airway smooth muscle thickening and contractile protein
      expression, and prevents tracheal hypercontractility. This study demonstrates
      that tiotropium also fully prevented allergen-induced mucous gland hypertrophy,
      and partially reduced the increase in MUC5AC-positive goblet cell numbers and
      eosinophil infiltration. Treatment with budesonide also prevented airway smooth
      muscle thickening, contractile protein expression, tracheal hypercontractility
      and mucous gland hypertrophy, and partially reduced MUC5AC-positive goblet cell
      numbers and eosinophilia. This study demonstrates that tiotropium and budesonide
      are similarly effective in inhibiting several aspects of airway remodelling,
      providing further evidence that the beneficial effects of tiotropium bromide
      might exceed those of bronchodilation.

PMID- 17537781
TI  - In vivo assessment of the human sperm acrosome reaction and the expression of
      glycodelin-A in human endometrium after levonorgestrel-emergency contraceptive
      pill administration.
AB  - BACKGROUND: The objectives were firstly to assess acrosome reaction (AR) status
      of spermatozoa following uterine flushing, secondly to measure levonorgestrel
      (LNG) levels in serum and in uterine flushing fluid and finally to measure
      endometrial glycodelin-A expression after administration of LNG as a form of
      emergency contraception (EC). METHODS: Forty-eight experiments were conducted on
      15 regularly menstruating women. Four groups were formed based on different
      intercourse to treatment interval and treatment to recovery of spermatozoa and
      the biopsies. RESULTS: Twenty-four and forty-eight hours after treatment, there
      were 14.5 +/- 3.9 x 10(6) and 17.3 +/- 6.8 x 10(6) sperm recovered from the
      uterus, respectively. There were no differences between the AR rate and the
      endometrial glycodelin-A staining intensity in an LNG or placebo treated cycles.
      The LNG in uterine flushing medium represented 1.38% of the values observed in
      serum 24 h after the LNG intake. CONCLUSIONS: Twenty-four and forty-eight hours
      after administration of EC, neither the proportion of AR sperm, nor the
      glycodelin-A level was influenced by 1.5 mg of LNG. LNG did not impair the
      cervical mucus either because viable spermatozoa were found in the genital tract
      36-60 h after coitus and 24-48 h after LNG intake. The mechanism of action of LNG
      as EC remains unknown.

PMID- 17537782
TI  - Quality of life and psychological well being in polycystic ovary syndrome.
AB  - BACKGROUND: Polycystic ovary syndrome (PCOS) is associated with poor quality of
      life (QoL) and high levels of depression. Existing research is confounded by
      small sample sizes and inconsistent use of control groups. METHODS: Depression
      and QoL were assessed in women with PCOS and healthy controls (n = 1359). The
      polycystic ovary syndrome health-related QoL questionnaire (PCOSQ) was modified
      to include an acne subscale. RESULTS: Seventy-one percentage of women with PCOS
      who were taking anti-androgen (AA) medication and 67% not taking AA medication
      were classified as depressed. Women with PCOS had lower QoL on all seven factors
      of the modified PCOSQ (emotional disturbance, weight, infertility, acne,
      menstrual symptoms, menstrual predictability and hirsutism). Weight was the
      largest contributor to poor QoL for women taking and not taking AA medication.
      Women taking AA medications, independent of diagnosis, generally had better QoL
      than women not taking them. CONCLUSIONS: This large study refines our
      understanding of depression and QoL in PCOS and demonstrates the need to
      regularly review the psychological health of women with PCOS.

PMID- 17537783
TI  - The accuracy of accredited glaucoma optometrists in the diagnosis and treatment
      recommendation for glaucoma.
AB  - AIM: To compare the diagnostic performance of accredited glaucoma optometrists
      (AGO) for both the diagnosis of glaucoma and the decision to treat with that of
      routine hospital eye care, against a reference standard of expert opinion (a
      consultant ophthalmologist with a special interest in glaucoma). METHODS: A
      directly comparative, masked, performance study was undertaken in Grampian,
      Scotland. Of 165 people invited to participate, 100 (61%) were examined. People
      suspected of having glaucoma underwent, within one month, a full ophthalmic
      assessment in both a newly established community optometry led glaucoma
      management scheme and a consultant led hospital eye service. RESULTS: Agreement
      between the AGO and the consultant ophthalmologist in diagnosing glaucoma was
      substantial (89%; kappa = 0.703, SE = 0.083). Agreement over the need for
      treatment was also substantial (88%; kappa = 0.716, SE = 0.076). The agreement
      between the trainee ophthalmologists and the consultant ophthalmologist in the
      diagnosis of glaucoma and treatment recommendation was moderate (83%, kappa =
      0.541, SE = 0.098, SE = 0.98; and 81%, kappa = 0.553, SE = 0.90, respectively).
      The diagnostic accuracy of the optometrists in detecting glaucoma in this
      population was high for specificity (0.93 (95% confidence interval, 0.85 to
      0.97)) but lower for sensitivity (0.76 (0.57 to 0.89)). Performance was similar
      when accuracy was assessed for treatment recommendation (sensitivity 0.73 (0.57
      to 0.85); specificity 0.96 (0.88 to 0.99)). The differences in sensitivity and
      specificity between AGO and junior ophthalmologist were not statistically
      significant. CONCLUSIONS: Community optometrists trained in glaucoma provided
      satisfactory decisions regarding diagnosis and initiation of treatment for
      glaucoma. With such additional training in glaucoma, optometrists are at least as
      accurate as junior ophthalmologists but some cases of glaucoma are missed.

PMID- 17537784
TI  - Non-responders to bevacizumab (Avastin) therapy of choroidal neovascular lesions.
AB  - AIMS: To determine the characteristics of "non-responders" to intravitreal
      bevacizumab treatment in choroidal neovascularisation (CNV). METHODS: Forty-three
      patients with visual loss due to neovascular age-related macular disease (ARMD)
      (44 eyes) underwent intravitreal injections of 1.25 mg (0.05 ml) bevacizumab and
      were followed up every 4 weeks for 2, 3 or 6 months. Re-injection was performed
      when persistent leakage of the CNV was determined by fluorescein angiography and
      retinal oedema was assessed by optical coherence tomography (OCT). Non-responders
      were defined as those patients having reduced or stable visual acuity at the last
      follow-up. RESULTS: 45% of the patients were non-responders. In this group the
      initial CNV size was significantly larger than in the responders. Initial reading
      ability was significantly lower in non-responders, but the initial foveal oedema
      was similar in both groups. Gains in mean visual acuity and reading ability were
      independent of lesion type. The proportion of non-responders to responders in the
      different lesion type groups was equally distributed. Only patients with the
      classic type of CNV seemed to respond better. CONCLUSIONS: In this study initial
      reasons for non-responders to intravitreal bevacizumab treatment in CNV are
      given. The efficiency of bevacizumab depends on initial lesion size and initial
      reading ability, but is independent of the amount of intraretinal and subretinal
      fluid. There was no general ineffectiveness of bevacizumab with any particular
      lesion type.

PMID- 17537785
TI  - Intravenous administration of clonidine reduces intraocular pressure and alters
      ocular blood flow.
AB  - AIM: To evaluate the effect of intravenously administered clonidine on ocular
      blood flow in healthy volunteers. METHODS: A randomised, double-masked, placebo
      controlled, two-way crossover study was performed in 12 healthy young volunteers.
      Clonidine (0.2 microg/kg/min) or placebo was administered intravenously over 10
      minutes. The effects of clonidine were studied at baseline and up to 150 minutes
      after infusion. Ocular haemodynamics were measured using laser Doppler flowmetry,
      laser Doppler velocimetry and a retinal vessel analyser. RESULTS: Clonidine
      significantly decreased mean arterial pressure (MAP) and intraocular pressure
      (IOP). Calculated ocular perfusion pressure decreased significantly by -8.7+/
      8.7% after infusion of clonidine (p<0.01 vs placebo). Retinal arterial diameters
      increased by +4.4+/-2.7% (p = 0.012 vs placebo), whereas no significant change
      was observed in retinal veins. Red blood cell velocity decreased by -16+/-14%
      (p<0.01 vs placebo) after infusion of clonidine. Hence, calculated retinal blood
      flow decreased by -14+/-12% (p = 0.033 vs placebo). Choroidal blood flow
      increased by +18+/-19% (p<0.01 vs placebo) and optic nerve head blood flow
      increased by +16+/-23% (p = 0.046 vs placebo) 30 minutes after administration of
      clonidine but both returned to baseline thereafter. CONCLUSION: The short-time
      increase in choroidal and optic nerve head blood flow indicates a transient
      vasodilatory effect of clonidine due to an unknown mechanism. The decrease in
      retinal blood flow indicates clonidine-induced vasoconstriction in the retinal
      microvasculature.

PMID- 17537786
TI  - Sensorineural hearing loss in a patient with HLA-B27 sclero-uveitis.

PMID- 17537787
TI  - Mef2s are required for thick filament formation in nascent muscle fibres.
AB  - During skeletal muscle differentiation, the actomyosin motor is assembled into
      myofibrils, multiprotein machines that generate and transmit force to cell ends.
      How expression of muscle proteins is coordinated to build the myofibril is
      unknown. Here we show that zebrafish Mef2d and Mef2c proteins are required
      redundantly for assembly of myosin-containing thick filaments in nascent muscle
      fibres, but not for the earlier steps of skeletal muscle fibre differentiation,
      elongation, fusion or thin filament gene expression. mef2d mRNA and protein is
      present in myoblasts, whereas mef2c expression commences in muscle fibres.
      Knockdown of both Mef2s with antisense morpholino oligonucleotides or in mutant
      fish blocks muscle function and prevents sarcomere assembly. Cell transplantation
      and heat-shock-driven rescue reveal a cell-autonomous requirement for Mef2 within
      fibres. In nascent fibres, Mef2 drives expression of genes encoding thick, but
      not thin, filament proteins. Among genes analysed, myosin heavy and light chains
      and myosin-binding protein C require Mef2 for normal expression, whereas actin,
      tropomyosin and troponin do not. Our findings show that Mef2 controls skeletal
      muscle formation after terminal differentiation and define a new maturation step
      in vertebrate skeletal muscle development at which thick filament gene expression
      is controlled.

PMID- 17537788
TI  - Adenylyl cyclase-dependent axonal targeting in the olfactory system.
AB  - The vertebrate olfactory bulb is a remarkably organized neuronal structure, in
      which hundreds of functionally different sensory inputs are organized into a
      highly stereotyped topographical map. How this wiring is achieved is not yet
      understood. Here, we show that the olfactory bulb topographical map is modified
      in adenylyl cyclase 3 (adenylate cyclase 3)-deficient mice. In these mutants,
      axonal projection targets corresponding to specific odorant receptors are
      disorganized, are no longer exclusively innervated by functionally identical
      axonal projections and shift dramatically along the anteroposterior axis of the
      olfactory bulb. Moreover, the cyclase depletion leads to the prevention of
      neuropilin 1 (Nrp1) expression in olfactory sensory neuron axonal projections.
      Taken together, our data point to a major role played by a crucial element of the
      odorant-induced transduction cascade, adenylyl cyclase 3, in the targeting of
      olfactory sensory neuron axons towards the brain. This mechanism probably
      involves the regulation of receptor genes known to be crucial in axonal guidance
      processes.

PMID- 17537789
TI  - Wnt/beta-catenin signaling regulates nephron induction during mouse kidney
      development.
AB  - Mammalian nephrons form as a result of a complex morphogenesis and patterning of
      a simple epithelial precursor, the renal vesicle. Renal vesicles are established
      from a mesenchymal progenitor population in response to inductive signals.
      Several lines of evidence support the sequential roles of two Wnt family members,
      Wnt9b and Wnt4, in renal vesicle induction. Using genetic approaches to
      specifically manipulate the activity of beta-catenin within the mesenchymal
      progenitor pool in mice, we investigated the potential role of the canonical Wnt
      pathway in these inductive events. Progenitor-cell-specific removal of beta
      catenin activity completely blocked both the formation of renal vesicles and the
      expected molecular signature of an earlier inductive response. By contrast,
      activation of stabilized beta-catenin in the same cell population causes ectopic
      expression of mesenchymal induction markers in vitro and functionally replaces
      the requirement for Wnt9b and Wnt4 in their inductive roles in vivo. Thus,
      canonical Wnt signaling is both necessary and sufficient for initiating and
      maintaining inductive pathways mediated by Wnt9b and Wnt4. However, the failure
      of induced mesenchyme with high levels of beta-catenin activity to form
      epithelial structures suggests that modulating canonical signaling may be crucial
      for the cellular transition to the renal vesicle.

PMID- 17537790
TI  - Physiological Notch signaling promotes gliogenesis in the developing peripheral
      and central nervous systems.
AB  - Constitutive activation of the Notch pathway can promote gliogenesis by
      peripheral (PNS) and central (CNS) nervous system progenitors. This raises the
      question of whether physiological Notch signaling regulates gliogenesis in vivo.
      To test this, we conditionally deleted Rbpsuh (Rbpj) from mouse PNS or CNS
      progenitors using Wnt1-Cre or Nestin-Cre. Rbpsuh encodes a DNA-binding protein
      (RBP/J) that is required for canonical signaling by all Notch receptors. In most
      regions of the developing PNS and spinal cord, Rbpsuh deletion caused only mild
      defects in neurogenesis, but severe defects in gliogenesis. These resulted from
      defects in glial specification or differentiation, not premature depletion of
      neural progenitors, because we were able to culture undifferentiated progenitors
      from the PNS and spinal cord despite their failure to form glia in vivo. In
      spinal cord progenitors, Rbpsuh was required to maintain Sox9 expression during
      gliogenesis, demonstrating that Notch signaling promotes the expression of a
      glial-specification gene. These results demonstrate that physiological Notch
      signaling is required for gliogenesis in vivo, independent of the role of Notch
      in the maintenance of undifferentiated neural progenitors.

PMID- 17537791
TI  - The RhoGAP RGA-2 and LET-502/ROCK achieve a balance of actomyosin-dependent
      forces in C. elegans epidermis to control morphogenesis.
AB  - Embryonic morphogenesis involves the coordinate behaviour of multiple cells and
      requires the accurate balance of forces acting within different cells through the
      application of appropriate brakes and throttles. In C. elegans, embryonic
      elongation is driven by Rho-binding kinase (ROCK) and actomyosin contraction in
      the epidermis. We identify an evolutionary conserved, actin microfilament
      associated RhoGAP (RGA-2) that behaves as a negative regulator of LET-502/ROCK.
      The small GTPase RHO-1 is the preferred target of RGA-2 in vitro, and acts
      between RGA-2 and LET-502 in vivo. Two observations show that RGA-2 acts in
      dorsal and ventral epidermal cells to moderate actomyosin tension during the
      first half of elongation. First, time-lapse microscopy shows that loss of RGA-2
      induces localised circumferentially oriented pulling on junctional complexes in
      dorsal and ventral epidermal cells. Second, specific expression of RGA-2 in
      dorsal/ventral, but not lateral, cells rescues the embryonic lethality of rga-2
      mutants. We propose that actomyosin-generated tension must be moderated in two
      out of the three sets of epidermal cells surrounding the C. elegans embryo to
      achieve morphogenesis.

PMID- 17537792
TI  - The ECM protein nephronectin promotes kidney development via integrin alpha8beta1
      mediated stimulation of Gdnf expression.
AB  - Development of the metanephric kidney crucially depends on proper interactions
      between cells and the surrounding extracellular matrix. For example, we showed
      previously that in the absence of alpha8beta1 integrin, invasion by the ureteric
      bud into the metanephric mesenchyme is inhibited, resulting in renal agenesis.
      Here we present genetic evidence that the extracellular matrix protein
      nephronectin is an essential ligand that engages alpha8beta1 integrin during
      early kidney development. We show that embryos lacking a functional nephronectin
      gene frequently display kidney agenesis or hypoplasia, which can be traced to a
      delay in the invasion of the metanephric mesenchyme by the ureteric bud at an
      early stage of kidney development. Significantly, we detected no defects in
      extracellular matrix organization in the nascent kidneys of the nephronectin
      mutants. Instead, we found that Gdnf expression was dramatically reduced in both
      nephronectin- and alpha8 integrin-null mutants specifically in the metanephric
      mesenchyme at the time of ureteric bud invasion. We show that this reduction is
      sufficient to explain the agenesis and hypoplasia observed in both mutants.
      Interestingly, the reduction in Gdnf expression is transient, and its resumption
      presumably enables the nephronectin-deficient ureteric buds to invade the
      metanephric mesenchyme and begin branching. Our results thus place nephronectin
      and alpha8beta1 integrin in a pathway that regulates Gdnf expression and is
      essential for kidney development.

PMID- 17537793
TI  - The transcription factors Nkx6.1 and Nkx6.2 possess equivalent activities in
      promoting beta-cell fate specification in Pdx1+ pancreatic progenitor cells.
AB  - Despite much progress in identifying transcriptional regulators that control the
      specification of the different pancreatic endocrine cell types, the
      spatiotemporal aspects of endocrine subtype specification have remained largely
      elusive. Here, we address the mechanism by which the transcription factors Nkx6.1
      (Nkx6-1) and Nkx6.2 (Nkx6-2) orchestrate development of the endocrine alpha- and
      beta-cell lineages. Specifically, we assayed for the rescue of insulin-producing
      beta-cells in Nkx6.1 mutant mice upon restoring Nkx6 activity in select
      progenitor cell populations with different Nkx6-expressing transgenes. Beta-cell
      formation and maturation was restored when Nkx6.1 was expressed in multipotential
      Pdx1(+) pancreatic progenitors, whereas no rescue was observed upon expression in
      committed Ngn3(+) (Neurog3(+)) endocrine progenitors. Although not excluding
      additional roles downstream of Ngn3, this finding suggests a first requirement
      for Nkx6.1 in specifying beta-cell progenitors prior to Ngn3 activation.
      Surprisingly, although Nkx6.2 only compensates for Nkx6.1 in alpha-but not in
      beta-cell development in Nkx6.1(-/-) mice, a Pdx1-promoter-driven Nkx6.2
      transgene had the same ability to rescue beta-cells as the Pdx1-Nkx6.1 transgene.
      This demonstrates that the distinct requirements for Nkx6.1 and Nkx6.2 in
      endocrine differentiation are a consequence of their divergent spatiotemporal
      expression domains rather than their biochemical activities and implies that both
      Nkx6.1 and Nkx6.2 possess alpha- and beta-cell-specifying activities.

PMID- 17537794
TI  - Cxcl12/Cxcr4 chemokine signaling is required for placode assembly and sensory
      axon pathfinding in the zebrafish olfactory system.
AB  - Positioning neurons in the right places and wiring axons to the appropriate
      targets are essential events for establishment of neural circuits. In the
      zebrafish olfactory system, precursors of olfactory sensory neurons (OSNs)
      assemble into a compact cluster to form the olfactory placode. Subsequently, OSNs
      differentiate and extend their axons to the presumptive olfactory bulb with high
      precision. In this study, we aim to elucidate the molecular mechanism underlying
      these two developmental processes. cxcr4b, encoding a chemokine receptor, is
      expressed in the migrating olfactory placodal precursors, and cxcl12a (SDF-1a),
      encoding a ligand for Cxcr4b, is expressed in the abutting anterior neural plate.
      The expression of cxcr4b persists in the olfactory placode at the initial phase
      of OSN axon pathfinding. At this time, cxcl12a is expressed along the placode
      telencephalon border and at the anterior tip of the telencephalon, prefiguring
      the route and target of OSN axons, respectively. Interfering with Cxcl12a/Cxcr4b
      signaling perturbs the assembly of the olfactory placode, resulting in the
      appearance of ventrally displaced olfactory neurons. Moreover, OSN axons
      frequently fail to exit the olfactory placode and accumulate near the placode
      telencephalon border in the absence of Cxcr4b-mediated signaling. These data
      indicate that chemokine signaling contributes to both the olfactory placode
      assembly and the OSN axon pathfinding in zebrafish.

PMID- 17537795
TI  - EEL-1, a Hect E3 ubiquitin ligase, controls asymmetry and persistence of the SKN
      1 transcription factor in the early C. elegans embryo.
AB  - During early divisions of the C. elegans embryo, many maternally supplied
      determinants accumulate asymmetrically, and this asymmetry is crucial for proper
      cell fate specification. SKN-1, a transcription factor whose message is
      maternally supplied to the embryo, specifies the mesendodermal cell fate. In the
      2-cell embryo, SKN-1 is expressed at a higher level in the posterior cell. This
      asymmetry becomes more pronounced at the 4-cell stage, when SKN-1 is high in the
      posterior cell's daughters and low in the daughters of the anterior blastomere.
      To date, the direct mechanisms that control SKN-1 distribution remain unknown. In
      this report, we identify eel-1, which encodes a putative Hect E3 ubiquitin ligase
      that shares several domains of similarity to the mammalian E3 ligase Mule. EEL-1
      binds SKN-1 and appears to target SKN-1 for degradation. EEL-1 has two functions
      in regulating SKN-1 during early embryogenesis. First, eel-1 promotes the spatial
      asymmetry of SKN-1 accumulation at the 2- and 4-cell stages. Second, eel-1 acts
      in all cells to downregulate SKN-1 from the 12- to the 28-cell stage. Although
      loss of eel-1 alone causes a reduction in SKN-1 asymmetry at the 2-cell stage,
      the function of eel-1 in both the spatial and temporal regulation of SKN-1 is
      redundant with the activities of other genes. These data strongly suggest that
      multiple, functionally redundant pathways cooperate to ensure precise control of
      SKN-1 asymmetry and persistence in the early embryo.

PMID- 17537796
TI  - Wnt signaling is a key mediator of Cdx1 expression in vivo.
AB  - In the mouse, Cdx1 is essential for normal anteroposterior vertebral patterning
      through regulation of a subset of Hox genes. Retinoic acid (RA) and certain Wnts
      have also been implicated in vertebral patterning, although the relationship
      between these signaling pathways and the regulation of mesodermal Hox gene
      expression is not fully understood. Prior work has shown that Cdx1 is a direct
      target of both Wnt and retinoid signaling pathways, and might therefore act to
      relay these signals to the Hox genes. Wnt and RA are believed to impact on Cdx1
      through an atypical RA-response element (RARE) and Lef/Tcf-response elements
      (LRE), respectively, in the proximal promoter. To address the roles of these
      regulatory motifs and pathways, we derived mice mutated for the LRE or the LRE
      plus the RARE. In contrast to RARE-null mutants, which exhibit limited vertebral
      defects, LRE-null and LRE+RARE-null mutants exhibited vertebral malformations
      affecting the entire cervical region that closely phenocopied the malformations
      seen in Cdx1-null mutants. Mutation of the LRE also greatly reduced induction of
      Cdx1 by RA, demonstrating a requirement for Wnt signaling in the regulation of
      this gene by retinoids. LRE and LRE+RARE mutants also exhibited vertebral
      fusions, suggesting a defect in somitogenesis. As Wnt signaling is implicated in
      somitogenesis upstream of the Notch pathway, it is conceivable that Cdx1 might
      play a role in this process. However, none of the Notch pathway genes assessed
      was overtly affected.

PMID- 17537797
TI  - Genetic subdivision of the tectum and cerebellum into functionally related
      regions based on differential sensitivity to engrailed proteins.
AB  - The genetic pathways that partition the developing nervous system into functional
      systems are largely unknown. The engrailed (En) homeobox transcription factors
      are candidate regulators of this process in the dorsal midbrain (tectum) and
      anterior hindbrain (cerebellum). En1 mutants lack most of the tectum and
      cerebellum and die at birth, whereas En2 mutants are viable with a smaller
      cerebellum and foliation defects. Our previous studies indicated that the
      difference in phenotypes is due to the earlier expression of En1 as compared with
      En2, rather than differences in protein function, since knock-in mice expressing
      En2 in place of En1 have a normal brain. Here, we uncovered a wider spectrum of
      functions for the En genes by generating a series of En mutant mice. First, using
      a conditional allele we demonstrate that En1 is required for cerebellum
      development only before embryonic day 9, but plays a sustained role in forming
      the tectum. Second, by removing the endogenous En2 gene in the background of En1
      knock-in alleles, we show that Drosophila en is not sufficient to sustain
      midbrain and cerebellum development in the absence of En2, whereas En2 is more
      potent than En1 in cerebellum development. Third, based on a differential
      sensitivity to the dose of En1/2, our studies reveal a genetic subdivision of the
      tectum into its two functional systems and the medial cerebellum into four
      regions that have distinct circuitry and molecular coding. Our study suggests
      that an ;engrailed code' is integral to partitioning the tectum and cerebellum
      into functional domains.

PMID- 17537798
TI  - Crk-associated substrate (Cas) signaling protein functions with integrins to
      specify axon guidance during development.
AB  - Members of the Cas family of Src homology 3 (SH3)-domain-containing cytosolic
      signaling proteins are crucial regulators of actin cytoskeletal dynamics in non
      neuronal cells; however, their neuronal functions are poorly understood. Here, we
      identify a Drosophila Cas (DCas), find that Cas proteins are highly expressed in
      neurons and show that DCas is required for correct axon guidance during
      development. Functional analyses reveal that Cas specifies axon guidance by
      regulating the degree of fasciculation among axons. These guidance defects are
      similar to those observed in integrin mutants, and genetic analysis shows that
      integrins function together with Cas to facilitate axonal defasciculation. These
      results strongly support Cas proteins working together with integrins in vivo to
      direct axon guidance events.

PMID- 17537799
TI  - Adrenal development is initiated by Cited2 and Wt1 through modulation of Sf-1
      dosage.
AB  - It has been proposed that the mammalian adrenal cortex and gonad are derived from
      the same primordium present during early urogenital development. Molecular
      pathways involved in the differentiation of the adrenal cortex from the
      adrenogonadal primordium (AGP) have yet to be determined. Here we show in mice
      that the transcription co-factor Cited2 is required for the specification of the
      adrenal cortex from the AGP. We present genetic and molecular evidence
      demonstrating that Cited2 interacts with the transcription factor Wt1 to
      stimulate expression of the nuclear hormone receptor Sf-1 (Nr5a1) in the AGP
      prior to the separation between gonad and adrenal cortex. We show a direct
      correlation between the expression levels of Sf-1 in the AGP and the defects in
      adrenal development found in mice with different Cited2 and Wt1 mutant
      backgrounds. Analysis of embryos heterozygous for mutations in both Sf-1 and
      Cited2 confirmed that these genes act in the same pathway during adrenal
      development. Our studies reveal a regulatory mechanism in which Cited2 acts as a
      Wt1 co-factor to increase, at a critical time in embryogenesis, the levels of the
      essential transcription factor Sf-1 in the AGP above the threshold required to
      determine adrenal development. These results highlight the importance of
      transcription factor dosage in organogenesis and the role of transcription co
      factors such as Cited2 in determining the levels of these factors.

PMID- 17537800
TI  - BMP signals control limb bud interdigital programmed cell death by regulating FGF
      signaling.
AB  - In vertebrate limbs that lack webbing, the embryonic interdigit region is removed
      by programmed cell death (PCD). Established models suggest that bone
      morphogenetic proteins (BMPs) directly trigger such PCD, although no direct
      genetic evidence exists for this. Alternatively, BMPs might indirectly affect PCD
      by regulating fibroblast growth factors (FGFs), which act as cell survival
      factors. Here, we inactivated the mouse BMP receptor gene Bmpr1a specifically in
      the limb bud apical ectodermal ridge (AER), a source of FGF activity. Early
      inactivation completely prevents AER formation. However, inactivation after limb
      bud initiation causes an upregulation of two AER-FGFs, Fgf4 and Fgf8, and a loss
      of interdigital PCD leading to webbed limbs. To determine whether excess FGF
      signaling inhibits interdigit PCD in these Bmpr1a mutant limbs, we performed
      double and triple AER-specific inactivations of Bmpr1a, Fgf4 and Fgf8. Webbing
      persists in AER-specific inactivations of Bmpr1a and Fgf8 owing to elevated Fgf4
      expression. Inactivation of Bmpr1a, Fgf8 and one copy of Fgf4 eliminates webbing.
      We conclude that during normal embryogenesis, BMP signaling to the AER indirectly
      regulates interdigit PCD by regulating AER-FGFs, which act as survival factors
      for the interdigit mesenchyme.

PMID- 17537801
TI  - Notch signalling is needed to maintain, but not to initiate, the formation of
      prosensory patches in the chick inner ear.
AB  - Notch signalling is well-known to mediate lateral inhibition in inner ear sensory
      patches, so as to generate a balanced mixture of sensory hair cells and
      supporting cells. Recently, however, we have found that ectopic Notch activity at
      an early stage can induce the formation of ectopic sensory patches. This suggests
      that Notch activity may have two different functions in normal ear development,
      acting first to promote the formation of the prosensory patches, and then later
      to regulate hair-cell production within the patches. The Notch ligand Serrate1
      (Jag1 in mouse and humans) is expressed in the patches from an early stage and
      may provide Notch activation during the prosensory phase. Here, we test whether
      Notch signalling is actually required for prosensory patch development. When we
      block Notch activation in the chick embryo using the gamma-secretase inhibitor
      DAPT, we see a complete loss of prosensory epithelial cells in the anterior
      otocyst, where they are diverted into a neuroblast fate via failure of Delta1
      dependent lateral inhibition. The cells of the posterior prosensory patch remain
      epithelial, but expression of Sox2 and Bmp4 is drastically reduced. Expression of
      Serrate1 here is initially almost normal, but subsequently regresses. The patches
      of sensory hair cells that eventually develop are few and small. We suggest that,
      in normal development, factors other than Notch activity initiate Serrate1
      expression. Serrate1, by activating Notch, then drives the expression of Sox2 and
      Bmp4, as well as expression of the Serrate1 gene itself. The positive feedback
      maintains Notch activation and thereby preserves and perhaps extends the
      prosensory state, leading eventually to the development of normal sensory
      patches.

PMID- 17537802
TI  - Endocardium is necessary for cardiomyocyte movement during heart tube assembly.
AB  - Embryonic heart formation requires the union of bilateral populations of
      cardiomyocytes and their reorganization into a simple tube. Little is known about
      the morphogenetic mechanisms that coordinate assembly of the heart tube and
      determine its dimensions. Using time-lapse confocal microscopy to track
      individual cardiomyocyte movements in the zebrafish embryo, we identify two
      morphologically and genetically separable phases of cell movement that coordinate
      heart tube assembly. First, all cardiomyocytes undergo coherent medial movement.
      Next, peripherally located cardiomyocytes change their direction of movement,
      angling toward the endocardial precursors and thereby establishing the initial
      circumference of the nascent heart tube. These two phases of cardiomyocyte
      behavior are independently regulated. Furthermore, we find that myocardial
      endocardial interactions influence the second phase by regulating the induction,
      direction and duration of cardiomyocyte movement. Thus, the endocardium plays a
      crucial early role in cardiac morphogenesis, organizing cardiomyocytes into a
      configuration appropriate for heart tube assembly. Together, our data reveal a
      dynamic cellular mechanism by which tissue interactions establish organ
      architecture.

PMID- 17537803
TI  - Chemotherapeutic stress selectively activates NF-kappa B-dependent AKT and VEGF
      expression in liver cancer-derived endothelial cells.
AB  - Targeting endothelial cells (EC) that line tumor blood vessels forms the basis
      for metronomic therapy and is a promising new strategy for the treatment of
      cancer. Genetic and phenotypic differences between tumor-derived and normal ECs
      indicate that targeting tumor ECs may be therapeutically useful. In the present
      study, we examined differences in responses to chemotherapy in microvascular EC
      lines from tumoral (T-EC) and normal (N-EC) mouse liver tissues. The identity of
      these cells was confirmed by immunocytochemistry for EC markers, such as vascular
      endothelial-cadherin and CD31 for both types of ECs, and the tumor-endothelial
      specific marker tumor endothelial marker-7 for T-EC. The involvement of Akt in NF
      kappaB-dependent angiogenesis was different between N-EC and T-EC.
      Chemotherapeutic stress increased angiogenesis in T-EC, but not N-EC via an NF
      kappaB-Akt-dependent manner. Both NF-kappaB and Akt were involved in enhanced
      survival and migration in T-EC in response to chemotherapeutic stress. Moreover,
      Akt was involved in NF-kappaB-dependent VEGF expression and angiogenesis. These
      studies, showing differences in cellular responses to chemotherapy in tumor
      derived ECs, indicate that specific therapies targeting these cells may be
      therapeutically useful for liver cancers.

PMID- 17537804
TI  - Activation and inactivation of the volume-sensitive taurine leak pathway in
      NIH3T3 fibroblasts and Ehrlich Lettre ascites cells.
AB  - Hypotonic exposure provokes the mobilization of arachidonic acid, production of
      ROS, and a transient increase in taurine release in Ehrlich Lettre cells. The
      taurine release is potentiated by H(2)O(2) and the tyrosine phosphatase inhibitor
      vanadate and reduced by the phospholipase A(2) (PLA(2)) inhibitors bromoenol
      lactone (BEL) and manoalide, the 5-lipoxygenase (5-LO) inhibitor ETH-615139, the
      NADPH oxidase inhibitor diphenyl iodonium (DPI), and antioxidants. Thus, swelling
      induced taurine efflux in Ehrlich Lettre cells involves Ca(2+)-independent
      (iPLA(2))/secretory PLA(2) (sPLA(2)) plus 5-LO activity and modulation by ROS.
      Vanadate and H(2)O(2) stimulate arachidonic acid mobilization and vanadate
      potentiates ROS production in Ehrlich Lettre cells and NIH3T3 fibroblasts under
      hypotonic conditions. However, vanadate-induced potentiation of the volume
      sensitive taurine efflux is, in both cell types, impaired in the presence of BEL
      and DPI and following restoration of the cell volume. Thus, potentiation of the
      volume-sensitive taurine efflux pathway following inhibition of tyrosine
      phosphatase activity reflects increased arachidonic acid mobilization and ROS
      production for downstream signaling. Vanadate delays the inactivation of volume
      sensitive taurine efflux in NIH3T3 cells, and this delay is impaired in the
      presence of DPI. Vanadate has no effect on the inactivation of swelling-induced
      taurine efflux in Ehrlich Lettre cells. It is suggested that increased tyrosine
      phosphorylation of regulatory components of NADPH oxidase leads to increased ROS
      production and a subsequent delay in inactivation of the volume-sensitive taurine
      efflux pathway and that NADPH oxidase or antioxidative capacity differ between
      NIH3T3 and Ehrlich Lettre cells.

PMID- 17537805
TI  - Volume change of the ocular lens during accommodation.
AB  - During accommodation, mammalian lenses change shape from a rounder configuration
      (near focusing) to a flatter one (distance focusing). Thus the lens must have the
      capacity to change its volume, capsular surface area, or both. Because lens
      topology is similar to a torus, we developed an approach that allows volume
      determination from the lens cross-sectional area (CSA). The CSA was obtained from
      photographs taken perpendicularly to the lenticular anterior-posterior (A-P) axis
      and computed with software. We calculated the volume of isolated bovine lenses in
      conditions simulating accommodation by forcing shape changes with a custom-built
      stretching device in which the ciliary body-zonulae-lens complex (CB-Z-L) was
      placed. Two measurements were taken (CSA and center of mass) to calculate volume.
      Mechanically stretching the CB-Z-L increased the equatorial length and decreased
      the A-P length, CSA, and lens volume. The control parameters were restored when
      the lenses were stretched and relaxed in an aqueous physiological solution, but
      not when submerged in oil, a condition with which fluid leaves the lens and does
      not reenter. This suggests that changes in lens CSA previously observed in humans
      could have resulted from fluid movement out of the lens. Thus accommodation may
      involve changes not only in capsular surface but also in volume. Furthermore, we
      calculated theoretical volume changes during accommodation in models of human
      lenses using published structural parameters. In conclusion, we suggest that
      impediments to fluid flow between the aquaporin-rich lens fibers and the lens
      surface could contribute to the aging-related loss of accommodative power.

PMID- 17537807
TI  - Mitochondrial alterations in human gastric carcinoma cell line.
AB  - We compared mitochondrial function, morphology, and proteome in the rat normal
      gastric cell line RGM-1 and the human gastric cancer cell line AGS. Total numbers
      and cross-sectional sizes of mitochondria were smaller in AGS cells. Mitochondria
      in AGS cells were deformed and consumed less oxygen. Confocal microscopy
      indicated that the mitochondrial inner membrane potential was hyperpolarized and
      the mitochondrial Ca(2+) concentration was elevated in AGS cells. Interestingly,
      two-dimensional electrophoresis proteomics on the mitochondria-enriched fraction
      revealed high expression of four mitochondrial proteins in AGS cells: ubiquinol
      cytochrome c reductase, mitochondrial short-chain enoyl-coenzyme A hydratase-1,
      heat shock protein 60, and mitochondria elongation factor Tu. The results provide
      clues as to the mechanism of the mitochondrial changes in cancer at the protein
      level and may serve as potential cancer biomarkers in mitochondria.

PMID- 17537806
TI  - Isoproterenol increases sorting of parotid gland cargo proteins to the
      basolateral pathway.
AB  - Exocrine cells have an essential function of sorting secreted proteins into the
      correct secretory pathway. A clear understanding of sorting in salivary glands
      would contribute to the correct targeting of therapeutic transgenes. The present
      work investigated whether there is a change in the relative proportions of basic
      proline-rich protein (PRP) and acidic PRPs in secretory granules in response to
      chronic isoproterenol treatment, and whether this alters the sorting of
      endogenous cargo proteins. Immunoblot analysis of secretory granules from rat
      parotids found a large increase of basic PRP over acidic PRPs in response to
      chronic isoproterenol treatment. Pulse chase experiments demonstrated that
      isoproterenol also decreased regulated secretion of newly synthesized secretory
      proteins, including PRPs, amylase and parotid secretory protein. This decreased
      efficiency of the apical regulated pathway may be mediated by alkalization of the
      secretory granules since it was reversed by treatment with mild acid. We also
      investigated changes in secretion through the basolateral (endocrine) pathways. A
      significant increase in parotid secretory protein and salivary amylase was
      detected in sera of isoproterenol-treated animals, suggesting increased routing
      of the regulated secretory proteins to the basolateral pathway. These studies
      demonstrate that shifts of endogenous proteins can modulate regulated secretion
      and sorting of cargo proteins.

PMID- 17537808
TI  - Patch Finder Plus (PFplus): a web server for extracting and displaying positive
      electrostatic patches on protein surfaces.
AB  - Positively charged electrostatic patches on protein surfaces are usually
      indicative of nucleic acid binding interfaces. Interestingly, many proteins which
      are not involved in nucleic acid binding possess large positive patches on their
      surface as well. In some cases, the positive patches on the protein are related
      to other functional properties of the protein family. PatchFinderPlus (PFplus)
      http://pfp.technion.ac.il is a web-based tool for extracting and displaying
      continuous electrostatic positive patches on protein surfaces. The input required
      for PFplus is either a four letter PDB code or a protein coordinate file in PDB
      format, provided by the user. PFplus computes the continuum electrostatics
      potential and extracts the largest positive patch for each protein chain in the
      PDB file. The server provides an output file in PDB format including a list of
      the patch residues. In addition, the largest positive patch is displayed on the
      server by a graphical viewer (Jmol), using a simple color coding.

PMID- 17537809
TI  - Characterization of the sequence specificity of the R1Bm endonuclease domain by
      structural and biochemical studies.
AB  - R1Bm is a long interspersed element (LINE) inserted into a specific sequence
      within 28S rDNA of the silkworm genome. Of two open reading frames (ORFs) of
      R1Bm, ORF2 encodes a reverse transcriptase (RT) and an endonuclease (EN) domain
      which digests specifically both top and bottom strand of the target sequence in
      28S rDNA. To elucidate the sequence specificity of EN domain of R1Bm (R1Bm EN),
      we examined the cleavage tendency for the target sequences, and found that 5'
      A(G/C)(A/T)!(A/G)T-3' is the consensus sequence (! = cleavage site). We also
      determined the crystal structure of R1Bm EN at 2.0 A resolution. Its structure
      was basically similar to AP endonuclease family, but had a special beta-hairpin
      at the edge of the DNA binding surface, which is a common feature among EN of
      LINEs. Point-mutations on the DNA binding surface of R1Bm EN significantly
      decreased the cleavage activities, but did not affect the sequence recognition in
      most residues. However, two mutants Y98A and N180A had altered cleavage patterns,
      suggesting an important role of these residues (Y98 and N180) for the sequence
      recognition of R1Bm EN. In addition, Y98A mutant showed another cleavage pattern,
      that implies de novo design of novel sequence-specific EN.

PMID- 17537810
TI  - CodonO: codon usage bias analysis within and across genomes.
AB  - Synonymous codon usage biases are associated with various biological factors,
      such as gene expression level, gene length, gene translation initiation signal,
      protein amino acid composition, protein structure, tRNA abundance, mutation
      frequency and patterns, and GC compositions. Quantification of codon usage bias
      helps understand evolution of living organisms. A codon usage bias pipeline is
      demanding for codon usage bias analyses within and across genomes. Here we
      present a CodonO webserver service as a user-friendly tool for codon usage bias
      analyses across and within genomes in real time. The webserver is available at
      http//www.sysbiology.org/CodonO. CONTACT: wanhenry@yahoo.com.

PMID- 17537811
TI  - Profiling the DNA-binding specificities of engineered Cys2His2 zinc finger
      domains using a rapid cell-based method.
AB  - The C2H2 zinc finger is the most commonly utilized framework for engineering DNA
      binding domains with novel specificities. Many different selection strategies
      have been developed to identify individual fingers that possess a particular DNA
      binding specificity from a randomized library. In these experiments, each finger
      is selected in the context of a constant finger framework that ensures the
      identification of clones with a desired specificity by properly positioning the
      randomized finger on the DNA template. Following a successful selection, multiple
      zinc-finger clones are typically recovered that share similarities in the
      sequences of their DNA-recognition helices. In principle, each of the clones
      isolated from a selection is a candidate for assembly into a larger multi-finger
      protein, but to date a high-throughput method for identifying the most specific
      candidates for incorporation into a final multi-finger protein has not been
      available. Here we describe the development of a specificity profiling system
      that facilitates rapid and inexpensive characterization of engineered zinc-finger
      modules. Moreover, we demonstrate that specificity data collected using this
      system can be employed to rationally design zinc fingers with improved DNA
      binding specificities.

PMID- 17537812
TI  - PrimerZ: streamlined primer design for promoters, exons and human SNPs.
AB  - PrimerZ (http://genepipe.ngc.sinica.edu.tw/primerz/) is a web application
      dedicated primarily to primer design for genes and human SNPs. PrimerZ accepts
      genes by gene name or Ensembl accession code, and SNPs by dbSNP rs or AFFY_Probe
      IDs. The promoter and exon sequence information of all gene transcripts fetched
      from the Ensembl database (http://www.ensembl.org) are processed before being
      passed on to Primer3 (http://frodo.wi.mit.edu/cgi-bin/primer3/primer3_www.cgi)
      for individual primer design. All results returned from Primer 3 are organized
      and integrated in a specially designed web page for easy browsing. Besides the
      web page presentation, csv text file export is also provided for enhanced user
      convenience. PrimerZ automates highly standard but tedious gene primer design to
      improve the success rate of PCR experiments. More than 2000 primers have been
      designed with PrimerZ at our institute since 2004 and the success rate is over
      70%. The addition of several new features has made PrimerZ even more useful to
      the research community in facilitating primer design for promoters, exons and
      SNPs.

PMID- 17537813
TI  - MobilomeFINDER: web-based tools for in silico and experimental discovery of
      bacterial genomic islands.
AB  - MobilomeFINDER (http://mml.sjtu.edu.cn/MobilomeFINDER) is an interactive online
      tool that facilitates bacterial genomic island or 'mobile genome' (mobilome)
      discovery; it integrates the ArrayOme and tRNAcc software packages. ArrayOme
      utilizes a microarray-derived comparative genomic hybridization input data set to
      generate 'inferred contigs' produced by merging adjacent genes classified as
      'present'. Collectively these 'fragments' represent a hypothetical 'microarray
      visualized genome (MVG)'. ArrayOme permits recognition of discordances between
      physical genome and MVG sizes, thereby enabling identification of strains rich in
      microarray-elusive novel genes. Individual tRNAcc tools facilitate automated
      identification of genomic islands by comparative analysis of the contents and
      contexts of tRNA sites and other integration hotspots in closely related
      sequenced genomes. Accessory tools facilitate design of hotspot-flanking primers
      for in silico and/or wet-science-based interrogation of cognate loci in
      unsequenced strains and analysis of islands for features suggestive of foreign
      origins; island-specific and genome-contextual features are tabulated and
      represented in schematic and graphical forms. To date we have used MobilomeFINDER
      to analyse several Enterobacteriaceae, Pseudomonas aeruginosa and Streptococcus
      suis genomes. MobilomeFINDER enables high-throughput island identification and
      characterization through increased exploitation of emerging sequence data and PCR
      based profiling of unsequenced test strains; subsequent targeted yeast
      recombination-based capture permits full-length sequencing and detailed
      functional studies of novel genomic islands.

PMID- 17537814
TI  - MYBS: a comprehensive web server for mining transcription factor binding sites in
      yeast.
AB  - Correct interactions between transcription factors (TFs) and their binding sites
      (TFBSs) are of central importance to gene regulation. Recently developed
      chromatin-immunoprecipitation DNA chip (ChIP-chip) techniques and the
      phylogenetic footprinting method provide ways to identify TFBSs with high
      precision. In this study, we constructed a user-friendly interactive platform for
      dynamic binding site mapping using ChIP-chip data and phylogenetic footprinting
      as two filters. MYBS (Mining Yeast Binding Sites) is a comprehensive web server
      that integrates an array of both experimentally verified and predicted position
      weight matrixes (PWMs) from eleven databases, including 481 binding motif
      consensus sequences and 71 PWMs that correspond to 183 TFs. MYBS users can search
      within this platform for motif occurrences (possible binding sites) in the
      promoters of genes of interest via simple motif or gene queries in conjunction
      with the above two filters. In addition, MYBS enables users to visualize in
      parallel the potential regulators for a given set of genes, a feature useful for
      finding potential regulatory associations between TFs. MYBS also allows users to
      identify target gene sets of each TF pair, which could be used as a starting
      point for further explorations of TF combinatorial regulation. MYBS is available
      at http://cg1.iis.sinica.edu.tw/~mybs/.

PMID- 17537815
TI  - Cellular antisense activity of peptide nucleic acid (PNAs) targeted to HIV-1
      polypurine tract (PPT) containing RNA.
AB  - DNA and RNA oligomers that contain stretches of guanines can associate to form
      stable secondary structures including G-quadruplexes. Our study shows that the
      (UUAAAAGAAAAGGGGGGAU) RNA sequence, from the human immunodeficiency virus type 1
      (HIV-1 polypurine tract or PPT sequence) forms in vitro a stable folded structure
      involving the G-run. We have investigated the ability of pyrimidine peptide
      nucleic acid (PNA) oligomers targeted to the PPT sequence to invade the folded
      RNA and exhibit biological activity at the translation level in vitro and in
      cells. We find that PNAs can form stable complexes even with the structured PPT
      RNA target at neutral pH. We show that T-rich PNAs, namely the tridecamer-I PNA
      (C4T4CT4) forms triplex structures whereas the C-rich tridecamer-II PNA (TC6T4CT)
      likely forms a duplex with the target RNA. Interestingly, we find that both C
      rich and T-rich PNAs arrested in vitro translation elongation specifically at the
      PPT target site. Finally, we show that T-rich and C-rich tridecamer PNAs that
      have been identified as efficient and specific blockers of translation elongation
      in vitro, specifically inhibit translation in streptolysin-O permeabilized cells
      where the PPT target sequence has been introduced upstream the reporter
      luciferase gene.

PMID- 17537817
TI  - Uracil-DNA glycosylases SMUG1 and UNG2 coordinate the initial steps of base
      excision repair by distinct mechanisms.
AB  - DNA glycosylases UNG and SMUG1 excise uracil from DNA and belong to the same
      protein superfamily. Vertebrates contain both SMUG1 and UNG, but their distinct
      roles in base excision repair (BER) of deaminated cytosine (U:G) are still not
      fully defined. Here we have examined the ability of human SMUG1 and UNG2 (nuclear
      UNG) to initiate and coordinate repair of U:G mismatches. When expressed in
      Escherichia coli cells, human UNG2 initiates complete repair of deaminated
      cytosine, while SMUG1 inhibits cell proliferation. In vitro, we show that SMUG1
      binds tightly to AP-sites and inhibits AP-site cleavage by AP-endonucleases.
      Furthermore, a specific motif important for the AP-site product binding has been
      identified. Mutations in this motif increase catalytic turnover due to reduced
      product binding. In contrast, the highly efficient UNG2 lacks product-binding
      capacity and stimulates AP-site cleavage by APE1, facilitating the two first
      steps in BER. In summary, this work reveals that SMUG1 and UNG2 coordinate the
      initial steps of BER by distinct mechanisms. UNG2 is apparently adapted to rapid
      and highly coordinated repair of uracil (U:G and U:A) in replicating DNA, while
      the less efficient SMUG1 may be more important in repair of deaminated cytosine
      (U:G) in non-replicating chromatin.

PMID- 17537816
TI  - A new connection of mRNP biogenesis and export with transcription-coupled repair.
AB  - Although DNA repair is faster in the transcribed strand of active genes, little
      is known about the possible contribution of mRNP biogenesis and export in
      transcription-coupled repair (TCR). Interestingly, mutants of THO, a
      transcription complex involved in maintenance of genome integrity, mRNP
      biogenesis and export, were recently found to be deficient in nucleotide excision
      repair. In this study we show by molecular DNA repair analysis, that Sub2-Yra1
      and Thp1-Sac3, two main mRNA export complexes, are required for efficient TCR in
      yeast. Careful analysis revealed that THO mutants are also specifically affected
      in TCR. Ribozyme-mediated mRNA self-cleavage between two hot spots for UV damage
      showed that efficient TCR does not depend on the nascent mRNA, neither in wild
      type nor in mutant cells. Along with severe UV damage-dependent loss in
      processivity, RNAPII was found binding to chromatin upon UV irradiation in THO
      mutants, suggesting that RNAPII remains stalled at DNA lesions. Furthermore,
      Def1, a factor responsible for the degradation of stalled RNAPII, appears
      essential for the viability of THO mutants subjected to DNA damage. Our results
      indicate that RNAPII is not proficient for TCR in mRNP biogenesis and export
      mutants, opening new perspectives on our knowledge of TCR in eukaryotic cells.

PMID- 17537818
TI  - EVALLER: a web server for in silico assessment of potential protein
      allergenicity.
AB  - Bioinformatics testing approaches for protein allergenicity, involving amino acid
      sequence comparisons, have evolved appreciably over the last several years to
      increased sophistication and performance. EVALLER, the web server presented in
      this article is based on our recently published 'Detection based on Filtered
      Length-adjusted Allergen Peptides' (DFLAP) algorithm, which affords in silico
      determination of potential protein allergenicity of high sensitivity and
      excellent specificity. To strengthen bioinformatics risk assessment in
      allergology EVALLER provides a comprehensive outline of its judgment on a query
      protein's potential allergenicity. Each such textual output incorporates a
      scoring figure, a confidence numeral of the assignment and information on high-
      or low-scoring matches to identified allergen-related motifs, including their
      respective location in accordingly derived allergens. The interface, built on a
      modified Perl Open Source package, enables dynamic and color-coded graphic
      representation of key parts of the output. Moreover, pertinent details can be
      examined in great detail through zoomed views. The server can be accessed at
      http://bioinformatics.bmc.uu.se/evaller.html.

PMID- 17537819
TI  - FRalanyzer: a tool for functional analysis of fold-recognition sequence-structure
      alignments.
AB  - We describe FRalanyzer (Fold Recognition alignment analyzer), a new web tool to
      visually inspect sequence-structure alignments in order to predict functionally
      important residues in a query sequence of unknown function. This tool is aimed at
      helping to infer functional relationships between a query sequence and a template
      structure, and is particularly useful in analyzing fold recognition (FR) results.
      Because similar folds do not necessarily share the same function, it is not
      always straightforward to infer a function from an FR result alone. Manual
      inspection of the FR sequence-structure alignment is often required in order to
      search for conservation of functionally important residues. FRalanyzer automates
      parts of this time-consuming process. FRalanyzer takes as input a sequence
      structure alignment, automatically searches annotated databases, displays
      functionally significant residues and highlights the functionally important
      positions that are identical in the alignment. FRalanyzer can also be used with
      sequence-structure alignments obtained by other methods, and with structure
      structure alignments obtained from structural comparison of newly determined 3D
      structures of unknown function. Fralanyzer is available at
      http://fralanyzer.cse.buffalo.edu/.

PMID- 17537820
TI  - FluGenome: a web tool for genotyping influenza A virus.
AB  - Influenza A viruses are hosted by numerous avian and mammalian species, which
      have shaped their evolution into distinct lineages worldwide. The viral genome
      consists of eight RNA segments that are frequently exchanged between different
      viruses via a process known as genetic reassortment. A complete genotype
      nomenclature is essential to describe gene segment reassortment. Specialized
      bioinformatic tools to analyze reassortment are not available, which hampers
      progress in understanding its role in host range, virulence and transmissibility
      of influenza viruses. To meet this need, we have developed a nomenclature to name
      influenza A genotypes and implemented a web server, FluGenome
      (http://www.flugenome.org/), for the assignment of lineages and genotypes.
      FluGenome provides functions for the user to interrogate the database in
      different modalities and get detailed reports on lineages and genotypes. These
      features make FluGenome unique in its ability to automatically detect genotype
      differences attributable to reassortment events in influenza A virus evolution.

PMID- 17537821
TI  - Melina II: a web tool for comparisons among several predictive algorithms to find
      potential motifs from promoter regions.
AB  - We present the second version of Melina, a web-based tool for promoter analysis.
      Melina II shows potential DNA motifs in promoter regions with a combination of
      several available programs, Consensus, MEME, Gibbs sampler, MDscan and Weeder, as
      well as several parameter settings. It allows running a maximum of four programs
      simultaneously, and comparing their results with graphical representations. In
      addition, users can build a weight matrix from a predicted motif and apply it to
      upstream sequences of several typical genomes (human, mouse, S. cerevisiae, E.
      coli, B. subtilis or A. thaliana) or to public motif databases (JASPAR or DBTBS)
      in order to find similar motifs. Melina II is a client/server system developed by
      using Adobe (Macromedia) Flash and is accessible over the web at
      http://melina.hgc.jp.

PMID- 17537822
TI  - CRISPRFinder: a web tool to identify clustered regularly interspaced short
      palindromic repeats.
AB  - Clustered regularly interspaced short palindromic repeats (CRISPRs) constitute a
      particular family of tandem repeats found in a wide range of prokaryotic genomes
      (half of eubacteria and almost all archaea). They consist of a succession of
      highly conserved regions (DR) varying in size from 23 to 47 bp, separated by
      similarly sized unique sequences (spacer) of usually viral origin. A CRISPR
      cluster is flanked on one side by an AT-rich sequence called the leader and
      assumed to be a transcriptional promoter. Recent studies suggest that this
      structure represents a putative RNA-interference-based immune system. Here we
      describe CRISPRFinder, a web service offering tools to (i) detect CRISPRs
      including the shortest ones (one or two motifs); (ii) define DRs and extract
      spacers; (iii) get the flanking sequences to determine the leader; (iv) blast
      spacers against Genbank database and (v) check if the DR is found elsewhere in
      prokaryotic sequenced genomes. CRISPRFinder is freely accessible at
      http://crispr.u-psud.fr/Server/CRISPRfinder.php.

PMID- 17537824
TI  - FastContact: a free energy scoring tool for protein-protein complex structures.
AB  - 'FastContact' is a server that estimates the direct electrostatic and desolvation
      interaction free energy between two proteins in units of kcal/mol. Users submit
      two proteins in PDB format, and the output is emailed back to the user in three
      files: one output file, and the two processed proteins. Besides the electrostatic
      and desolvation free energy, the server reports residue contact free energies
      that rapidly highlight the hotspots of the interaction and evaluates the van der
      Waals interaction using CHARMm. Response time is approximately 1 min. The server
      has been successfully tested and validated, scoring refined complex structures
      and blind sets of docking decoys, as well as proven useful predicting protein
      interactions. 'FastContact' offers unique capabilities from biophysical insights
      to scoring and identifying important contacts.

PMID- 17537823
TI  - Proteomic analysis of in vivo-assembled pre-mRNA splicing complexes expands the
      catalog of participating factors.
AB  - Previous compositional studies of pre-mRNA processing complexes have been
      performed in vitro on synthetic pre-mRNAs containing a single intron. To provide
      a more comprehensive list of polypeptides associated with the pre-mRNA splicing
      apparatus, we have determined the composition of the bulk pre-mRNA processing
      machinery in living cells. We purified endogenous nuclear pre-mRNA processing
      complexes from human and chicken cells comprising the massive (>200S)
      supraspliceosomes (a.k.a. polyspliceosomes). As expected, RNA components include
      a heterogeneous mixture of pre-mRNAs and the five spliceosomal snRNAs. In
      addition to known pre-mRNA splicing factors, 5' end binding factors, 3' end
      processing factors, mRNA export factors, hnRNPs and other RNA binding proteins,
      the protein components identified by mass spectrometry include RNA adenosine
      deaminases and several novel factors. Intriguingly, our purified
      supraspliceosomes also contain a number of structural proteins, nucleoporins,
      chromatin remodeling factors and several novel proteins that were absent from
      splicing complexes assembled in vitro. These in vivo analyses bring the total
      number of factors associated with pre-mRNA to well over 300, and represent the
      most comprehensive analysis of the pre-mRNA processing machinery to date.

PMID- 17537825
TI  - BioBayesNet: a web server for feature extraction and Bayesian network modeling of
      biological sequence data.
AB  - BioBayesNet is a new web application that allows the easy modeling and
      classification of biological data using Bayesian networks. To learn Bayesian
      networks the user can either upload a set of annotated FASTA sequences or a set
      of pre-computed feature vectors. In case of FASTA sequences, the server is able
      to generate a wide range of sequence and structural features from the sequences.
      These features are used to learn Bayesian networks. An automatic feature
      selection procedure assists in selecting discriminative features, providing an
      (locally) optimal set of features. The output includes several quality measures
      of the overall network and individual features as well as a graphical
      representation of the network structure, which allows to explore dependencies
      between features. Finally, the learned Bayesian network or another uploaded
      network can be used to classify new data. BioBayesNet facilitates the use of
      Bayesian networks in biological sequences analysis and is flexible to support
      modeling and classification applications in various scientific fields. The
      BioBayesNet server is available at http://biwww3.informatik.uni
      freiburg.de:8080/BioBayesNet/.

PMID- 17537826
TI  - Structure SNP (StSNP): a web server for mapping and modeling nsSNPs on protein
      structures with linkage to metabolic pathways.
AB  - SNPs located within the open reading frame of a gene that result in an alteration
      in the amino acid sequence of the encoded protein [nonsynonymous SNPs (nsSNPs)]
      might directly or indirectly affect functionality of the protein, alone or in the
      interactions in a multi-protein complex, by increasing/decreasing the activity of
      the metabolic pathway. Understanding the functional consequences of such changes
      and drawing conclusions about the molecular basis of diseases, involves
      integrating information from multiple heterogeneous sources including sequence,
      structure data and pathway relations between proteins. The data from NCBI's SNP
      database (dbSNP), gene and protein databases from Entrez, protein structures from
      the PDB and pathway information from KEGG have all been cross referenced into the
      StSNP web server, in an effort to provide combined integrated, reports about
      nsSNPs. StSNP provides 'on the fly' comparative modeling of nsSNPs with links to
      metabolic pathway information, along with real-time visual comparative analysis
      of the modeled structures using the Friend software application. The use of
      metabolic pathways in StSNP allows a researcher to examine possible disease
      related pathways associated with a particular nsSNP(s), and link the diseases
      with the current available molecular structure data. The server is publicly
      available at http://glinka.bio.neu.edu/StSNP/.

PMID- 17537827
TI  - CanPredict: a computational tool for predicting cancer-associated missense
      mutations.
AB  - Various cancer genome projects are underway to identify novel mutations that
      drive tumorigenesis. While these screens will generate large data sets, the
      majority of identified missense changes are likely to be innocuous passenger
      mutations or polymorphisms. As a result, it has become increasingly important to
      develop computational methods for distinguishing functionally relevant mutations
      from other variations. We previously developed an algorithm, and now present the
      web application, CanPredict (http://www.canpredict.org/ or
      http://www.cgl.ucsf.edu/Research/genentech/canpredict/), to allow users to
      determine if particular changes are likely to be cancer-associated. The impact of
      each change is measured using two known methods: Sorting Intolerant From Tolerant
      (SIFT) and the Pfam-based LogR.E-value metric. A third method, the Gene Ontology
      Similarity Score (GOSS), provides an indication of how closely the gene in which
      the variant resides resembles other known cancer-causing genes. Scores from these
      three algorithms are analyzed by a random forest classifier which then predicts
      whether a change is likely to be cancer-associated. CanPredict fills an important
      need in cancer biology and will enable a large audience of biologists to
      determine which mutations are the most relevant for further study.

PMID- 17537828
TI  - Drinking by parents, siblings, and friends as predictors of regular alcohol use
      in adolescents and young adults: a longitudinal twin-family study.
AB  - AIMS: The aim of this study was to examine whether the drinking habits of
      parents, siblings, and friends were related to regular drinking in adolescents
      and young adults, cross-sectionally as well as longitudinally. METHODS: Data of
      12-30-year-old twins from the Netherlands Twin Register were analysed.
      Information on regular drinking was collected in 1993, 1995, and 2000. Logistic
      regression analyses were conducted on cross-sectional data of 1993 (N=3760),
      short-term longitudinal data of 1993-95 (N=2919), and the long-term longitudinal
      data of 1993-2000 (N=1779). RESULTS: Results show that age, sex, and one's own
      previous drinking habits were important predictors of later-life regular
      drinking. Drinking habits of parents showed small but persistent positive
      associations. Alcohol use of the co-twin was strongly related to alcohol use of
      the participants, especially in the cross-sectional analyses, while alcohol use
      of additional siblings other than the co-twin was relatively unimportant. Cross
      sectionally, friends' alcohol use showed a high association with regular
      drinking, but this association decreased over time. CONCLUSION: Cross-sectional
      analyses showed that a substantial part (29%) of the variance in regular drinking
      habits of adolescents and young adults was explained by the drinking habits of
      family members and friends, in particular, by drinking of co-twins and friends.
      But, over time, drinking by family members and friends could only explain a
      relatively small part (4-5%) of the variance in adolescents' and young adults'
      alcohol use.

PMID- 17537829
TI  - Russian alcohol policy in the making.
AB  - AIMS: This paper examines implementation of the 2005 federal alcohol control law
      in the Russian Federation. METHODS: The documents on the Russian Federation
      federal legislation on the control of the production and turnover of ethyl
      alcohol, and ethyl alcohol containing products, news reports, research, and
      historical documents were gathered and analysed for implementation barriers.
      RESULTS: Consumption of alcoholic beverages, especially spirits, has been one the
      most significant public health problems in Russia for many centuries. Prior
      attempts to control alcohol consumption have been unsuccessful, in part due to
      the government's reliance on alcohol revenue, and its inability to implement
      creative and manageable solutions in the light of the high drinking rates.
      Implementation of this legislation has been a challenge in Russia because of
      administrative oversight, lack of organizational preparation, and corruption.
      CONCLUSIONS: The law discussed in this paper presented a window of opportunity to
      ameliorate the deteriorating health status and reverse the impending mortality
      crisis. However, a number of barriers presented substantial setbacks toward
      realization of this legislation.

PMID- 17537830
TI  - Response of the exocrine pancreas to the CCK on offspring rats of ethanol dams.
      Effects of folic acid.
AB  - AIMS: The aim of this study was to study the reverse effect of folic acid
      administered during gestation and lactation to ethanol-treated dams, on
      cholecystokinin Cholecystokinin (CCK) stimulus-secretion coupling in pancreatic
      exocrine secretion in offspring rats. METHODS: Animals were randomized into three
      groups: Control group (C) received water and basic diet during pregnancy and
      lactation period; ethanol-treated rats (E) received ethanol and basic diet; the
      ethanol+folic acid group (EF) received folic acid supplement concomitantly with
      ethanol administration. RESULTS: Body and pancreatic weight was lower in
      offsprings after ethanol treatment. Folic acid supplementation increased these
      parameters with respect to ethanol rats. After CCK stimulation, a significant
      decrease in amylase, lipase and chymotrypsin activities in the duodenal juice
      were detected in ethanol, this trend was partially corrected with folate
      supplementation. CONCLUSION: Ethanol exerts its action on exocrine pancreatic
      secretion by two pathways: 'per se' and diminishing the folic acid content,
      because a folic acid supplement in rats during pregnancy and lactation periods
      produces an advantageous effect on amylase, lipase and chymotrypsin secretion in
      their offspring. Although extrapolation from animal studies may be tenuous, the
      present findings may explain the use of folic acid in the prevention of ethanol
      induced damage by increasing the enzyme levels to adequate physiological
      concentrations.

PMID- 17537831
TI  - Prenatal alcohol exposure and the neuroapoptosis with long-term effect in visual
      cortex of mice.
AB  - AIMS: The prenatal ethanol exposure induced neuroapoptosis and neuron loss in
      visual cortex would be investigated in mice at P0, P7 and P14. METHODS:
      Intubating pregnant mice ethanol daily began on E5 and continued through the
      pup's birth. The neuroapoptosis in visual cortex was visualized by the caspase 3
      immunocytochemistry, and the neuron loss was observed with Nissl method as well.
      RESULTS: With prenatal ethanol exposure, the dose-dependent neuroapoptosis and
      neuron loss in visual cortex could be found at P0 and even at P7 and P14 as well.
      CONCLUSIONS: The prenatal ethanol exposure induced neuroapoptosis and neuron loss
      will persist into postnatal stage, and the long-term effect of neuroapoptosis
      might be one of the causes of postnatal neurobehavioural disturbances associated
      with fetal alcohol syndrome.

PMID- 17537832
TI  - Sildenafil citrate in the treatment of sexual dysfunction and its effect on
      quality of life in alcohol dependent men: preliminary findings.
AB  - BACKGROUND: Alcohol-dependent men commonly suffer from erectile dysfunction (ED)
      and men with ED are frequently chronic alcohol addicts. Sildenafil is used for
      treatment of ED caused by diverse factors. The aim of this study was to examine
      (i) the effect of sildenafil citrate (VIAGRA) on ED in alcohol dependent men, and
      (ii) whether the effective treatment of ED with sildenafil improves the patient's
      QoL and related emotional distress. METHODS: Fifty-four men with an ICD-10
      diagnosis of alcohol dependence (AD) and concomitant ED agreed to enter an open
      label trial, in which they were assigned to take 50 mg of sildenafil as add-on to
      a standard treatment for AD for 12 weeks. Fifty patients (92.3%) completed all
      baseline and endpoint assessments. Efficacy was evaluated using the International
      Index of Erectile Function (IIEF), Quality of Life Enjoyment and Satisfaction
      Questionnaire and General Health Questionnaire. RESULTS: At endpoint, total IIEF
      scores had improved significantly (Delta=16.9), reflecting a 42% improvement
      (P<0.0001). A significant increase in the mean scores of each sexual function
      domain was also noted among all subjects. Sildenafil's positive effect was
      accompanied by a significant improvement (P<0.001) in satisfaction with overall
      QoL and specific life-domains, as well as a significant reduction in emotional
      distress scores (P<0.001). CONCLUSION: The sildenafil add-on evaluated in this
      trial had a marked beneficial effect on ED and QoL, and was associated with a
      significant reduction in emotional distress among men with AD. The information
      obtained is valuable for both clinicians and policymakers in developing
      innovative therapeutic strategies for men with AD.

PMID- 17537833
TI  - Interleukin-6 alters the cellular responsiveness to clopidogrel, irinotecan, and
      oseltamivir by suppressing the expression of carboxylesterases HCE1 and HCE2.
AB  - Carboxylesterases constitute a class of enzymes that play important roles in the
      hydrolytic metabolism of drugs and other xenobiotics. Patients with liver
      conditions such as cirrhosis show increased secretion of proinflammatory
      cytokines [e.g., interleukin-6 (IL-6)] and decreased capacity of hydrolysis. In
      this study, we provide a molecular explanation linking cytokine secretion
      directly to the decreased capacity of hydrolytic biotransformation. In both
      primary hepatocytes and HepG2 cells, treatment with IL-6 decreased the expression
      of human carboxyl-esterases HCE1 and HCE2 by as much as 60%. The decreased
      expression occurred at both mRNA and protein levels, and it was confirmed by
      enzymatic assay. In cotransfection experiments, both HCE1 and HCE2 promoters were
      significantly repressed, and the repression was comparable with the decrease in
      HCE1 and HCE2 mRNA, suggesting that transrepression is responsible for the
      suppressed expression. In addition, pretreatment with IL-6 altered the cellular
      responsiveness in an opposite manner of overexpression of HCE1 and HCE2 toward
      various ester therapeutic agents (e.g., clopidogrel). Transfection of HCE1, for
      example, decreased the cytotoxicity induced by antithrombogenic agent
      clopidogrel, whereas pretreatment with IL-6 increased the cytotoxicity. Such a
      reversal was observed with other ester drugs, including anticancer agent
      irinotecan and anti-influenza agent oseltamivir. The altered cellular
      responsiveness was observed when drugs were assayed at sub- and low-micromolar
      concentrations, suggesting that suppressed expression of carboxylesterases by IL
      6 has profound pharmacological consequences, particularly with those that are
      hydrolyzed in an isoform-specific manner.

PMID- 17537834
TI  - Orexin-induced feeding requires NMDA receptor activation in the perifornical
      region of the lateral hypothalamus.
AB  - Food intake is stimulated following administration of orexin-A into the
      perifornical region of the lateral hypothalamus (LH/PFA). Orexin neurons
      originating in the LH/PFA interact with a number of hypothalamic systems known to
      influence food intake, including glutamatergic neurons. Glutamatergic systems in
      the LH/PFA were demonstrated to initiate feeding through N-methyl-d-aspartic acid
      (NMDA) receptors. Male Sprague-Dawley rats fitted with brain guide cannulas to
      the LH/PFA were used in two experiments. In the first experiment, a combination
      microdialysis/microinjection probe was used to deliver artificial cerebrospinal
      fluid (aCSF) or 500 pmol of orexin-A into the LH/PFA. Orexin-A increased
      interstitial glutamate to 143 +/- 12% of baseline (P < 0.05), which remained
      elevated over the 120-min collection period. In the second experiment, the NMDA
      receptor antagonist d-2-amino-5-phosphonopentanoic acid (d-AP5; 10 nmol) was
      administered before orexin-A. The orexin-induced increase in food intake (from
      1.1 +/- 0.4 to 3.2 +/- 0.5 g, P < 0.05) during the first hour was absent in rats
      receiving d-AP5 + orexin-A (1.2 +/- 0.5 g). There was no effect of d-AP5 alone on
      food intake. These data support glutamatergic systems in the LH/PFA mediating the
      feeding response to orexin-A through NMDA receptors.

PMID- 17537835
TI  - Inhibitory effects of excess sympathetic activity on parasympathetic vasodilation
      in the rat masseter muscle.
AB  - The present study was designed to examine the effect of sympathetic tonic
      activity on parasympathetic vasodilation evoked by the trigeminal-mediated reflex
      in the masseter muscle in urethane-anesthetized rats. Sectioning of the superior
      cervical sympathetic trunk (CST) ipsilaterally increased the basal level of blood
      flow in the masseter muscle (MBF). Electrical stimulation of the peripheral cut
      end of the CST for 2 min using 2-ms pulses ipsilaterally decreased in a dependent
      manner the intensity (0.5-10 V) and frequency (0.1-5 Hz) of the MBF. The CST
      stimulation for 2 min at <0.5 Hz with 5 V using 2-ms pulses seems to be
      comparable with the spontaneous activity in the CST fibers innervating the
      masseter vasculature, because this stimulation restored the basal level of the
      MBF to the presectioned values. Parasympathetic vasodilation evoked by electrical
      stimulation of the central cut end of the lingual nerve in the masseter muscle
      was markedly reduced by CST stimulation for 2 min with 5 V using 2-ms pulses in a
      frequency-dependent manner (0.5-5 Hz). Intravenous administration of phentolamine
      significantly reduced the vasoconstriction induced by CST stimulation in a dose
      dependent manner (0.1-1 mg/kg), but pretreatment with either phentolamine or
      propranolol failed to affect the sympathetic inhibition of the parasympathetic
      vasodilation. Our results suggest that 1) excess sympathetic activity inhibits
      parasympathetic vasodilation in the masseter muscle, and 2) alpha- and beta
      adrenoceptors do not contribute to sympathetic inhibition of parasympathetic
      vasodilation, and thus some other types of receptors must be involved in this
      response.

PMID- 17537836
TI  - Compensatory airway dilation and additive ventilatory augmentation mediated by
      dorsomedial medullary 5-hydroxytryptamine 2 receptor activity and hypercapnia.
AB  - 5-HT2 receptor activity in the hypoglossal nucleus and hypercapnia is associated
      with airway dilation. 5-HT neurons in the medullary raphe and hypercapnia are
      responsible for tidal volume change. In this study, the effects of 5-HT2
      receptors in the dorsomedial medulla oblongata (DMM), which receives projections
      from the medullary raphe, and hypercapnia on airway resistance and respiratory
      variables were studied in mice while monitoring 5-HT release in the DMM. A
      microdialysis probe was inserted into the DMM of anesthetized adult mice. Each
      mouse was placed in a double-chamber plethysmograph. After recovery from
      anesthesia, the mice were exposed to stepwise increases in CO(2) inhalation (5%,
      7%, and 9% CO(2) in O(2)) at 8-min intervals with a selective serotonin reuptake
      inhibitor, fluoxetine, or fluoxetine plus a 5-HT2 receptor antagonist, LY-53857
      in the DMM. In response to fluoxetine plus LY-53857 coperfusion, specific airway
      resistance was increased, and tidal volume and minute ventilation were decreased.
      CO(2) inhalation with fluoxetine plus LY-53857 coperfusion in the DMM largely
      decreased airway resistance and additively increased minute ventilation. Thus, 5
      HT2 receptor activity in the DMM increases basal levels of airway dilation and
      ventilatory volume, dependent on central inspiratory activity and the volume
      threshold of the inspiratory off-switch mechanism. Hypercapnia with low 5-HT2
      receptor activity in the DMM largely recovers airway dilation and additively
      increases ventilatory volume. Interaction between 5-HT2 receptor activity in the
      DMM and CO(2) drive may elicit a cycle of hyperventilation with airway dilation
      and hypoventilation with airway narrowing.

PMID- 17537838
TI  - Is programming of weight regulation immune to neonatal inflammation?

PMID- 17537837
TI  - Placental insufficiency results in temporal alterations in the renin angiotensin
      system in male hypertensive growth restricted offspring.
AB  - Reduced uterine perfusion initiated in late gestation in the rat results in
      intrauterine growth restriction (IUGR) and development of hypertension by 4 wk of
      age. We hypothesize that the renin angiotensin system (RAS), a regulatory system
      important in the long-term control of blood pressure, may be programmed by
      placental insufficiency and may contribute to the etiology of IUGR hypertension.
      We previously reported that RAS blockade abolished hypertension in adult IUGR
      offspring; however, the mechanisms responsible for the early phase of
      hypertension are unresolved. Therefore, the purpose of this study was to examine
      RAS involvement in early programmed hypertension and to determine whether
      temporal changes in RAS expression are observed in IUGR offspring. Renal renin
      and angiotensinogen mRNA expression were significantly decreased at birth (80 and
      60%, respectively); plasma and renal RAS did not differ in conjunction with
      hypertension (mean increase of 14 mmHg) in young IUGR offspring; however,
      hypertension (mean increase of 22 mmHg) in adult IUGR offspring was associated
      with marked increases in renal angiotensin-converting enzyme (ACE) activity
      (122%) and renal renin and angiotensinogen mRNA (7-fold and 7.4-fold,
      respectively), but no change in renal ANG II or angiotensin type 1 receptor. ACE
      inhibition (enalapril, 10 mg x kg(-1) x day(-1), administered from 2 to 4 wk of
      age) abolished hypertension in IUGR at 4 wk of age (decrease of 15 mmHg,
      respectively) with no significant depressor effect in control offspring.
      Therefore, temporal alterations in renal RAS are observed in IUGR offspring and
      may play a key role in the etiology of IUGR hypertension.

PMID- 17537839
TI  - Expression of cyclooxygenase-2 in urinary bladder in rats with cyclophosphamide
      induced cystitis.
AB  - These studies examined the expression of cyclooxygenase-2 (COX-2) expression in
      the urothelium and suburothelial space and detrusor from rats treated with
      cyclophosphamide (CYP) to induce acute (4 h), intermediate (48 h), or chronic (10
      day) cystitis. Western blot analysis and immunohistochemistry were used to
      demonstrate COX-2 expression. In whole mount preparations of urinary bladder,
      nerve fibers in the suburothelial plexus, and inflammatory cell infiltrates were
      characterized for COX-2 expression after CYP-induced cystitis. COX-2 expression
      significantly (P <or= 0.01) increased in the urothelium + suburothelium and
      detrusor smooth muscle with acute, intermediate, and chronic (10-day) CYP-induced
      cystitis, but expression in urothelium + suburothelium was significantly greater.
      CYP-induced upregulation of COX-2 showed by immunostaining in the urothelium +
      suburothelium was similar to that observed with Western blot analysis and also
      demonstrated COX-2 inflammatory cell infiltrates (CD86+) and nerve fibers (PGP+)
      in the suburothelial plexus. Although COX-2 expression was significantly (P <or=
      0.01) increased in detrusor smooth muscle, immunohistochemistry failed to
      demonstrate an obvious change in COX-2-immunoreactivity (IR) in detrusor muscle,
      but COX-2 inflammatory infiltrates were present throughout the detrusor. COX-2-IR
      nerve fibers exhibited increased density in the suburothelial plexus with acute
      or chronic CYP-induced cystitis. COX-2-IR macrophages (CD86+) were present
      throughout the urinary bladder with acute and chronic CYP-induced cystitis. These
      studies demonstrate cellular targets in the urinary bladder where COX-2
      inhibitors may act.

PMID- 17537840
TI  - Growth hormone-releasing hormone: cerebral cortical sleep-related EEG actions and
      expression.
AB  - Growth hormone-releasing hormone (GHRH), its receptor (GHRHR), and other members
      of the somatotropic axis are involved in non-rapid eye movement sleep (NREMS)
      regulation. Previously, studies established the involvement of hypothalamic
      GHRHergic mechanisms in NREMS regulation, but cerebral cortical GHRH mechanisms
      in sleep regulation remained uninvestigated. Here, we show that unilateral
      application of low doses of GHRH to the surface of the rat somatosensory cortex
      ipsilaterally decreased EEG delta wave power, while higher doses enhanced delta
      power. These actions of GHRH on EEG delta wave power occurred during NREMS but
      not during rapid eye movement sleep. Further, the cortical forms of GHRH and
      GHRHR were identical to those found in the hypothalamus and pituitary,
      respectively. Cortical GHRHR mRNA and protein levels did not vary across the day
      night cycle, whereas cortical GHRH mRNA increased with sleep deprivation. These
      results suggest that cortical GHRH and GHRHR have a role in the regulation of
      localized EEG delta power that is state dependent, as well as in their more
      classic hypothalamic role in NREMS regulation.

PMID- 17537841
TI  - Hyperglycemia impairs glucose and insulin regulation of nitric oxide production
      in glucose-inhibited neurons in the ventromedial hypothalamus.
AB  - Physiological changes in extracellular glucose, insulin, and leptin regulate
      glucose-excited (GE) and glucose-inhibited (GI) neurons in the ventromedial
      hypothalamus (VMH). Nitric oxide (NO) signaling, which is involved in the
      regulation of food intake and insulin signaling, is altered in obesity and
      diabetes. We previously showed that glucose and leptin inhibit NO production via
      the AMP-activated protein kinase (AMPK) pathway, while insulin stimulates NO
      production via the phosphatidylinositol-3-OH kinase (PI3K) pathway in VMH GI
      neurons. Hyperglycemia-induced inhibition of AMPK reduces PI3K signaling by
      activating the mammalian target of rapamycin (mTOR). We hypothesize that
      hyperglycemia impairs glucose and insulin-regulated NO production in VMH GI
      neurons. This hypothesis was tested in VMH neurons cultured in hyperglycemic
      conditions or from streptozotocin-induced type 1 diabetic rats using NO- and
      membrane potential-sensitive dyes. Neither decreased extracellular glucose from
      2.5 to 0.5 mM, nor 5 nM insulin increased NO production in VMH neurons in either
      experimental condition. Glucose- and insulin-regulated NO production was restored
      in the presence of the AMPK activator, 5-aminoimidazole-4-carboxamide-1-b-4
      ribofuranoside or the mTOR inhibitor rapamycin. Finally, decreased glucose and
      insulin did not alter membrane potential in VMH neurons cultured in hyperglycemic
      conditions or from streptozotocin-induced rats. These data suggest that
      hyperglycemia impairs glucose and insulin regulation of NO production through
      AMPK inhibition. Furthermore, glucose and insulin signaling pathways interact via
      the mTOR pathway.

PMID- 17537842
TI  - Estimation of the size and shape of GH secretory bursts in healthy women using a
      physiological estradiol clamp and variable-waveform deconvolution model.
AB  - Because estrogen production and age are strong covariates, distinguishing their
      individual impact on hypothalamo-pituitary regulation of growth hormone (GH)
      output is difficult. In addition, at fixed elimination kinetics, systemic GH
      concentration patterns are controlled by three major signal types [GH-releasing
      hormone (GHRH), GH-releasing peptide (GHRP, ghrelin), and somatostatin (SS)] and
      by four dynamic mechanisms [the number, mass (size), and shape (waveform) of
      secretory bursts and basal (time invariant) GH secretion]. The present study
      introduces an investigative strategy comprising 1) imposition of an experimental
      estradiol clamp in pre- (PRE) and postmenopausal (POST) women; 2) stimulation of
      fasting GH secretion by each of GHRH, GHRP-2 (a ghrelin analog), and l-arginine
      (to putatively limit SSergic restraint); and 3) implementation of a flexible
      waveform deconvolution model to estimate basal GH secretion simultaneously with
      the size and shape of secretory bursts, conditional on pulse number. The combined
      approach unveiled the following salient percent POST/PRE contrasts: 1) only 27%
      as much GH secreted in bursts during fasting (P < 0.001); 2) markedly attenuated
      burstlike GH secretion in response to bolus GHRP-2 (29%), bolus GHRH (30%), l
      arginine (37%), constant GHRP-2 (38%), and constant GHRH (42%) (age contrasts,
      0.0016 </= P </= 0.027); and 3) a 160% prolongation and 32% abbreviation of the
      time required to achieve maximal GH secretion after injection of l-arginine and
      bolus GHRP-2, respectively (both, P < 0.001). Accordingly, age selectively
      determines both the size (amount) and shape (waveform) of GH secretory bursts in
      healthy women independently of the short-term estrogen milieu.

PMID- 17537843
TI  - A PTH/PTHrP receptor antagonist blocks the hypercalcemic response to estradiol
      17beta.
AB  - Estradiol (E(2)) increases circulating calcium and phosphate levels in fish, thus
      acting as a hypercalcemic and hyperphosphatemic factor during periods of high
      calcium requirements, such as during vitellogenesis. Since parathyroid hormone
      (PTH)-related protein (PTHrP) has been shown to be calciotropic in fish, we
      hypothesized that the two hormones could be mediating the same process. Sea bream
      (Sparus auratus) juveniles receiving a single intraperitoneal injection of
      piscine PTHrP(1-34) showed an elevation in calcium plasma levels within 24 h. In
      contrast, injections of the PTH/PTHrP receptor antagonist PTHrP(7-34) decreased
      circulating levels of calcium in the same period. Intraperitoneal implants of
      estradiol-17beta (E(2); 10 microg/g) evoked significant increases of circulating
      plasma levels of calcium and phosphorus and a sustained increases of circulating
      plasma levels of PTHrP. However, a combined treatment of E(2) and PTHrP(7-34)
      evoked a markedly lower calcium response compared with E(2) alone. We conclude
      that PTHrP or a related peptide that binds the PTH/PTHrP receptor mediates, at
      least in part, the hypercalcemic effect of E(2) in calcium and phosphate balance
      in fish.

PMID- 17537844
TI  - Vascular bed-specific endothelium-dependent vasomomotor relaxation in the
      hagfish, Myxine glutinosa.
AB  - The last common ancestor of hagfish and gnathostomes was also the last common
      ancestor of all extant vertebrates that lived some time more than 500 million
      years ago. Features that are shared between hagfish and gnathostomes can be
      inferred to have already been present in this ancestral vertebrate. We recently
      reported that hagfish endothelium displays phenotypic heterogeneity in
      ultrastructure, lectin binding, and mechanisms of leukocyte adhesion. Thus,
      phenotypic cell heterogeneity evolved as an early feature of the endothelium. In
      the present study, we wanted to extend these observations by determining whether
      hagfish endothelium plays a role in mediating vasomotor tone. Response of
      mesenteric and skeletal muscle arteries to a variety of mediators was assayed by
      videomicroscopy. Phenylephrine and acetylcholine induced vasoconstriction of
      mesenteric and skeletal muscle arteries. Bradykinin (BK) and ADP promoted
      vasorelaxation in precontracted mesenteric arteries but not those from skeletal
      muscle. BK- and ADP-mediated vasorelaxation of the mesenteric artery was
      abrogated by mechanical denudation of the endothelium but was unaffected by N(G)
      nitro-L-arginine methyl ester. Indomethacin significantly inhibited the
      vasodilatory response to ADP but not BK. The nitric oxide donor sodium
      nitroprusside resulted in endothelium-independent relaxation of both mesenteric
      and skeletal muscle arteries. Together, these data suggest that site-specific
      endothelium-dependent vasorelaxation is an evolutionarily conserved property of
      this cell lineage.

PMID- 17537845
TI  - Hepatitis C virus p7 and NS2 proteins are essential for production of infectious
      virus.
AB  - Hepatitis C virus (HCV) infection is a global health concern affecting an
      estimated 3% of the world's population. Recently, cell culture systems have been
      established, allowing recapitulation of the complete virus life cycle for the
      first time. Since the HCV proteins p7 and NS2 are not predicted to be major
      components of the virion, nor are they required for RNA replication, we
      investigated whether they might have other roles in the viral life cycle. Here we
      utilize the recently described infectious J6/JFH chimera to establish that the p7
      and NS2 proteins are essential for HCV infectivity. Furthermore, unprocessed
      forms of p7 and NS2 were not required for this activity. Mutation of two
      conserved basic residues, previously shown to be important for the ion channel
      activity of p7 in vitro, drastically impaired infectious virus production. The
      protease domain of NS2 was required for infectivity, whereas its catalytic active
      site was dispensable. We conclude that p7 and NS2 function at an early stage of
      virion morphogenesis, prior to the assembly of infectious virus.

PMID- 17537846
TI  - General strategy for decoration of enveloped viruses with functionally active
      lipid-modified cytokines.
AB  - Viral particles preferentially incorporate extra- and intracellular constituents
      of host cell lipid rafts, a phenomenon central to pseudotyping. Based on this
      mechanism, we have developed a system for the predictable decoration of enveloped
      viruses with functionally active cytokines that circumvents the need to modify
      viral proteins themselves. Human interleukin-2 (hIL-2), hIL-4, human granulocyte
      macrophage colony-stimulating factor (hGM-CSF), and murine IL-2 (mIL-2) were used
      as model cytokines and fused at their C terminus to the
      glycosylphosphatidylinositol (GPI) acceptor sequence of human Fcgamma receptor
      III (CD16b). We show here that genetically modified cytokines are all well
      expressed on 293 producer cells. However, only molecules equipped with GPI
      anchors but not those linked to transmembrane/intracellular regions of type I
      membrane proteins are efficiently targeted to lipid rafts and consequently to
      virus-like particles (VLP) induced by Moloney murine leukemia virus Gag-Pol. hIL
      4::GPI and hGM-CSF::GPI coexpressed on VLP were found to differentiate monocytes
      towards dendritic cells. Apart from myeloid-committed cell types, VLP-bound
      cytokines also act efficiently on lymphocytes. hIL-2::GPI strongly costimulated T
      cell receptor (TCR)/CD3 dependent T-cell activation in vitro and mIL-2::GPI
      coactivated antigen-specific T cells in vivo. On a molar basis, the functional
      activity of VLP-bound hIL-2::GPI was found to be comparable to that of soluble
      hIL-2. VLP decorated with hIL-2::GPI and coexpressing a TCR/CD3 ligand have an IL
      2-specific activity of 5 x 10(4) units/mg protein. Virus particles decorated with
      lipid-modified cytokines might help to improve viral strains for vaccination
      purposes, the propagation of factor-dependent cell types, as well as gene
      transfer by viral systems in the future.

PMID- 17537847
TI  - Antibody binding in proximity to the receptor/glycoprotein complex leads to a
      basal level of virus neutralization.
AB  - Hypothetically, antibodies may neutralize enveloped viruses by diverse
      mechanisms, such as disruption of receptor binding, interference with
      conformational changes required for virus entry, steric hindrance, or virus
      aggregation. Here, we demonstrate that retroviral infection mediated by the avian
      sarcoma-leukosis virus (ASLV-A) envelope glycoproteins can be neutralized by an
      antibody directed against a functionally unimportant component of a chimeric
      receptor protein. Thus, the binding of an antibody in proximity to the retroviral
      envelope glycoprotein-receptor complex, without binding to the entry machinery
      itself, results in neutralization. This finding provides additional support for
      the hypothesis that steric hindrance is sufficient for antibody-mediated
      neutralization of retroviruses.

PMID- 17537848
TI  - Mamu-B*08-positive macaques control simian immunodeficiency virus replication.
AB  - Certain major histocompatibility complex (MHC) class I alleles are associated
      with the control of human immunodeficiency virus and simian immunodeficiency
      virus (SIV) replication. We have designed sequence-specific primers for detection
      of the rhesus macaque MHC class I allele Mamu-B*08 by PCR and screened a cohort
      of SIV-infected macaques for this allele. Analysis of 196 SIV(mac)239-infected
      Indian rhesus macaques revealed that Mamu-B*08 was significantly overrepresented
      in elite controllers; 38% of elite controllers were Mamu-B*08 positive compared
      to 3% of progressors (P = 0.00001). Mamu-B*08 was also associated with a 7.34
      fold decrease in chronic phase viremia (P = 0.002). Mamu-B*08-positive macaques
      may, therefore, provide a good model to understand the correlates of MHC class I
      allele-associated immune protection and viral containment in human elite
      controllers.

PMID- 17537849
TI  - Low immune activation despite high levels of pathogenic human immunodeficiency
      virus type 1 results in long-term asymptomatic disease.
AB  - Long-term asymptomatic human immunodeficiency virus (HIV)-infected individuals
      (LTA) usually have low viral load and low immune activation. To discern whether
      viral load or immune activation is dominant in determining progression to AIDS,
      we studied three exceptional LTA with high viral loads. HIV type 1 isolates from
      these LTA were as pathogenic as viruses from progressors in organ culture.
      Despite high viral loads, these LTA had low levels of proliferating and activated
      T cells compared to progressors, like other LTA. In contrast to those in
      progressors, HIV-specific CD4(+) T-cell responses in these LTA were maintained.
      Thus, low immune activation despite a high viral load preserved HIV-specific T
      cell responses and resulted in a long-term asymptomatic phenotype.

PMID- 17537850
TI  - De novo initiation of RNA synthesis by the arterivirus RNA-dependent RNA
      polymerase.
AB  - All plus-strand RNA viruses encode an RNA-dependent RNA polymerase (RdRp) that
      functions as the catalytic subunit of the viral replication/transcription
      complex, directing viral RNA synthesis in concert with other viral proteins and,
      sometimes, host proteins. RNA synthesis essentially can be initiated by two
      different mechanisms, de novo initiation and primer-dependent initiation. Most
      viral RdRps have been identified solely on the basis of comparative sequence
      analysis, and for many viruses the mechanism of initiation is unknown. In this
      study, using the family prototype equine arteritis virus (EAV), we address the
      mechanism of initiation of RNA synthesis in arteriviruses. The RdRp domains of
      the members of the arterivirus family, which are part of replicase subunit nsp9,
      were compared to coronavirus RdRps that belong to the same order of Nidovirales,
      as well as to other RdRps with known initiation mechanisms and three-dimensional
      structures. We report here the first successful expression and purification of an
      arterivirus RdRp that is catalytically active in the absence of other viral or
      cellular proteins. The EAV nsp9/RdRp initiates RNA synthesis by a de novo
      mechanism on homopolymeric templates in a template-specific manner. In addition,
      the requirements for initiation of RNA synthesis from the 3' end of the viral
      genome were studied in vivo using a reverse genetics approach. These studies
      suggest that the 3'-terminal nucleotides of the EAV genome play a critical role
      in viral RNA synthesis.

PMID- 17537851
TI  - Distinct gene expression profiling after infection of immature human monocyte
      derived dendritic cells by the attenuated poxvirus vectors MVA and NYVAC.
AB  - Although recombinants based on the attenuated poxvirus vectors MVA and NYVAC are
      currently in clinical trials, the nature of the genes triggered by these vectors
      in antigen-presenting cells is poorly characterized. Using microarray technology
      and various analysis conditions, we compared specific changes in gene expression
      profiling following MVA and NYVAC infection of immature human monocyte-derived
      dendritic cells (MDDC). Microarray analysis was performed at 6 h postinfection,
      since these viruses induced extensive cytopathic effects, rRNA breakdown, and
      apoptosis at late times postinfection. MVA- and NYVAC-infected MDDC shared
      upregulation of 195 genes compared to uninfected cells: MVA specifically
      upregulated 359 genes, and NYVAC upregulated 165 genes. Microarray comparison of
      NYVAC and MVA infection revealed 544 genes with distinct expression patterns
      after poxvirus infection and 283 genes specifically upregulated after MVA
      infection. Both vectors upregulated genes for cytokines, cytokine receptors,
      chemokines, chemokine receptors, and molecules involved in antigen uptake and
      processing, including major histocompatibility complex genes. mRNA levels for
      interleukin 12beta (IL-12beta), beta interferon, and tumor necrosis factor alpha
      were higher after MVA infection than after NYVAC infection. The expression
      profiles of transcription factors such as NF-kappaB/Rel and STAT were regulated
      similarly by both viruses; in contrast, OASL, MDA5, and IRIG-I expression
      increased only during MVA infection. Type I interferon, IL-6, and Toll-like
      receptor pathways were specifically induced after MVA infection. Following MVA or
      NYVAC infection in MDDC, we found similarities as well as differences between
      these virus strains in the expression of cellular genes with immunological
      function, which should have an impact when these vectors are used as recombinant
      vaccines.

PMID- 17537852
TI  - Dynein-dependent transport of the hantaan virus nucleocapsid protein to the
      endoplasmic reticulum-Golgi intermediate compartment.
AB  - In contrast to most negative-stranded RNA viruses, hantaviruses and other viruses
      in the family Bunyaviridae mature intracellularly, deriving the virion envelope
      from the endoplasmic reticulum (ER) or Golgi compartment. While it is generally
      accepted that Old World hantaviruses assemble and bud into the Golgi compartment,
      some studies with New World hantaviruses have raised the possibility of
      maturation at the plasma membrane as well. Overall, the steps leading to virion
      assembly remain largely undetermined for hantaviruses. Because hantaviruses do
      not have matrix proteins, the nucleocapsid protein (N) has been proposed to play
      a key role in assembly. Herein, we examine the intracellular trafficking and
      morphogenesis of the prototype Old World hantavirus, Hantaan virus (HTNV). Using
      confocal microscopy, we show that N colocalized with the ER-Golgi intermediate
      compartment (ERGIC) in HTNV-infected Vero E6 cells, not with the ER, Golgi
      compartment, or early endosomes. Brefeldin A, which effectively disperses the ER,
      the ERGIC, and Golgi membranes, redistributed N with the ERGIC, implicating
      membrane association; however, subcellular fractionation experiments showed the
      majority of N in particulate fractions. Confocal microscopy revealed that N was
      juxtaposed to and distributed along microtubules and, over time, became
      surrounded by vimentin cages. To probe cytoskeletal association further, we
      probed trafficking of N in cells treated with nocodazole and cytochalasin D,
      which depolymerize microtubules and actin, respectively. We show that nocodazole,
      but not cytochalasin D, affected the distribution of N and reduced levels of
      intracellular viral RNA. These results suggested the involvement of microtubules
      in trafficking of N, whose movement could occur via molecular motors such as
      dynein. Overexpression of dynamitin, which is associated with dynein-mediated
      transport, creates a dominant-negative phenotype blocking transport on
      microtubules. Overexpression of dynamitin reduced N accumulation in the
      perinuclear region, which further supports microtubule components in N
      trafficking. The combined results of these experiments support targeting of N to
      the ERGIC prior to its movement to the Golgi compartment and the requirement of
      an intact ERGIC for viral replication and, thus, the possibility of virus
      factories in this region.

PMID- 17537854
TI  - Reconstruction and function of ancestral center-of-tree human immunodeficiency
      virus type 1 proteins.
AB  - The extensive diversity of human immunodeficiency virus type 1 (HIV-1) and its
      capacity to mutate and escape host immune responses are major challenges for AIDS
      vaccine development. Ancestral sequences, which minimize the genetic distance to
      circulating strains, provide an opportunity to design immunogens with the
      potential to elicit broad recognition of HIV epitopes. We developed a
      phylogenetics-informed algorithm to reconstruct ancestral HIV sequences, called
      Center of Tree (COT). COT sequences have potentially significant benefits over
      isolate-based strategies, as they minimize the evolutionary distances to
      circulating strains. COT sequences are designed to surmount the potential
      pitfalls stemming from sampling bias with the consensus method and outlier bias
      with the most-recent-common-ancestor approach. We computationally derived COT
      sequences from circulating HIV-1 subtype B sequences for the genes encoding the
      major viral structural protein (Gag) and two regulatory proteins, Tat and Nef.
      COT genes were synthesized de novo and expressed in mammalian cells, and the
      proteins were characterized. COT Gag was shown to generate virus-like particles,
      while COT Tat transactivated gene expression from the HIV-1 long terminal repeat
      and COT Nef mediated downregulation of cell surface major histocompatibility
      complex class I. Thus, retrodicted ancestral COT proteins can retain the
      biological functions of extant HIV-1 proteins. Additionally, COT proteins were
      immunogenic, as they elicited antigen-specific cytotoxic T-lymphocyte responses
      in mice. These data support the utility of the COT approach to create novel and
      biologically active ancestral proteins as a starting point for studies of the
      structure, function, and biological fitness of highly variable genes, as well as
      for the rational design of globally relevant vaccine candidates.

PMID- 17537853
TI  - Interferon-mediated immunopathological events are associated with atypical innate
      and adaptive immune responses in patients with severe acute respiratory syndrome.
AB  - It is not understood how immune inflammation influences the pathogenesis of
      severe acute respiratory syndrome (SARS). One area of strong controversy is the
      role of interferon (IFN) responses in the natural history of SARS. The fact that
      the majority of SARS patients recover after relatively moderate illness suggests
      that the prevailing notion of deficient type I IFN-mediated immunity, with
      hypercytokinemia driving a poor clinical course, is oversimplified. We used
      proteomic and genomic technology to systematically analyze host innate and
      adaptive immune responses of 40 clinically well-described patients with SARS
      during discrete phases of illness from the onset of symptoms to discharge or a
      fatal outcome. A novel signature of high IFN-alpha, IFN-gamma, and IFN-stimulated
      chemokine levels, plus robust antiviral IFN-stimulated gene (ISG) expression,
      accompanied early SARS sequelae. As acute illness progressed, SARS patients
      entered a crisis phase linked to oxygen saturation profiles. The majority of SARS
      patients resolved IFN responses at crisis and expressed adaptive immune genes. In
      contrast, patients with poor outcomes showed deviated ISG and immunoglobulin gene
      expression levels, persistent chemokine levels, and deficient anti-SARS spike
      antibody production. We contend that unregulated IFN responses during acute-phase
      SARS may culminate in a malfunction of the switch from innate immunity to
      adaptive immunity. The potential for the use of the gene signatures we describe
      in this study to better assess the immunopathology and clinical management of
      severe viral infections, such as SARS and avian influenza (H5N1), is therefore
      worth careful examination.

PMID- 17537855
TI  - Characterization of fusion determinants points to the involvement of three
      discrete regions of both E1 and E2 glycoproteins in the membrane fusion process
      of hepatitis C virus.
AB  - Infection of eukaryotic cells by enveloped viruses requires the merging of viral
      and cellular membranes. Highly specific viral surface glycoproteins, named fusion
      proteins, catalyze this reaction by overcoming inherent energy barriers.
      Hepatitis C virus (HCV) is an enveloped virus that belongs to the genus
      Hepacivirus of the family Flaviviridae. Little is known about the molecular
      events that mediate cell entry and membrane fusion for HCV, although significant
      progress has been made due to recent developments in infection assays. Here,
      using infectious HCV pseudoparticles (HCVpp), we investigated the molecular basis
      of HCV membrane fusion. By searching for classical features of fusion peptides
      through the alignment of sequences from various HCV genotypes, we identified six
      regions of HCV E1 and E2 glycoproteins that present such characteristics. We
      introduced conserved and nonconserved amino acid substitutions in these regions
      and analyzed the phenotype of HCVpp generated with mutant E1E2 glycoproteins.
      This was achieved by (i) quantifying the infectivity of the pseudoparticles, (ii)
      studying the incorporation of E1E2 and their capacity to mediate receptor
      binding, and (iii) determining their fusion capacity in cell-cell and
      liposome/HCVpp fusion assays. We propose that at least three of these regions
      (i.e., at positions 270 to 284, 416 to 430, and 600 to 620) play a role in the
      membrane fusion process. These regions may contribute to the merging of viral and
      cellular membranes either by interacting directly with lipid membranes or by
      assisting the fusion process through their involvement in the conformational
      changes of the E1E2 complex at low pH.

PMID- 17537856
TI  - Characterization of Rift Valley fever virus transcriptional terminations.
AB  - Rift Valley fever virus (RVFV) (genus Phlebovirus, family Bunyaviridae) has a
      tripartite negative-strand genome and causes a mosquito-borne disease among
      humans and livestock in sub-Saharan African and Arabian Peninsula countries.
      Phlebovirus L, M, and N mRNAs are synthesized from the virus-sense RNA segments,
      while NSs mRNA is transcribed from the anti-virus-sense S segment. The present
      study determined the 3' termini of all RVFV mRNAs. The 3' termini of N and NSs
      mRNAs were mapped within the S-segment intergenic region and were complementary
      to each other by 30 to 60 nucleotides. The termini of M and L mRNAs were mapped
      within 122 to 107 nucleotides and 16 to 41 nucleotides, respectively, from the 5'
      ends of their templates. Viral RNA elements that control phlebovirus
      transcriptional terminations are largely unknown. Our studies suggested the
      importance of a pentanucleotide sequence, CGUCG, for N, NSs, and M mRNA
      transcription terminations. Homopolymeric tracts of C sequences, which were
      located upstream of the pentanucleotide sequence, promoted N and M mRNA
      terminations. Likewise, the homopolymeric tracts of G sequences that are found
      upstream of the pentanucleotide sequence promoted NSs mRNA termination. The L
      segment 5'-untranslated region (L-5' UTR) had neither the pentanucleotide
      sequence nor homopolymeric sequences, yet replacement of the S-segment intergenic
      region with the L-5' UTR exerted N mRNA termination in an infectious virus. The L
      5' UTR contained two 13-nucleotide-long complete complementary sequences, and
      their sequence complementarities were important for L mRNA termination. A
      computer-mediated RNA secondary structure analysis further suggested that RNA
      secondary structures formed by the sections of the two 13-nucleotide-long
      sequences and by the sequence between them may have a role in L mRNA termination.
      Our data demonstrated that viral RNA elements that govern L mRNA termination
      differed from those that regulate mRNA terminations in the M and S segments.

PMID- 17537857
TI  - Enterovirus 70 receptor utilization is controlled by capsid residues that also
      regulate host range and cytopathogenicity.
AB  - Enterovirus type 70, an etiologic agent of acute hemorrhagic conjunctivitis, may
      bind different cellular receptors depending on cell type. To understand how EV70
      receptor interaction is controlled, we studied two variants of the virus with
      distinct receptor utilization. EV70-Rmk, derived by passage in rhesus monkey
      kidney cells, replicates poorly in HeLa cells and does not cause cytopathic
      effects. Decay accelerating factor (DAF) is not a cell receptor for EV70-Rmk.
      Passage of EV70-Rmk in HeLa cells lead to isolation of EV70-Dne, which does not
      replicate in rhesus monkey kidney cells but grows to high titers in HeLa cells
      and causes cytopathic effects. DAF is sufficient for cell entry of EV70-Dne. EV70
      Rmk replicates in human eye and brain-derived cell lines, whereas the Dne strain
      replicates only in HeLa cells and in conjunctiva-derived 15C4 cells. The two EV70
      strains differ by five amino acid changes in the viral capsid. Single
      substitution of four of the five EV70-Rmk amino acids with the residue from EV70
      Dne leads to lytic replication in HeLa cells. Conversely, substitution of any of
      the five EV70-Dne amino acids with the EV70-Rmk amino acid does not alter
      replication in HeLa cells. Three of these capsid amino acids are predicted to be
      located in the canyon encircling the fivefold axis of symmetry, one amino acid is
      found at the fivefold axis of symmetry, and one is located the interior of the
      capsid. The five EV70 residues define a region of the capsid that controls viral
      host range, DAF utilization, and cytopathogenicity.

PMID- 17537859
TI  - A mutation on influenza C virus M1 protein affects virion morphology by altering
      the membrane affinity of the protein.
AB  - Reverse genetics has been documented for influenza A, B, and Thogoto viruses
      belonging to the family Orthomyxoviridae. We report here the reverse genetics of
      influenza C virus, another member of this family. The seven viral RNA (vRNA)
      segments of C/Ann Arbor/1/50 were expressed in 293T cells from cloned cDNAs,
      together with nine influenza C virus proteins. At 48 h posttransfection, the
      infectious titer of the culture supernatant was determined to be 2.51 x 10(3) 50%
      egg infectious doses/ml, which is lower than the number of influenza C virus-like
      particles (VLPs) (10(6)/ml) generated using the same system. By generating
      influenza C VLPs containing a given vRNA segment, we showed that each of the vRNA
      segments was similarly synthesized in the plasmid-transfected cells but that some
      segments were less efficiently incorporated into the VLPs. This finding leads us
      to speculate that the differences in incorporation efficiency into VLPs between
      segments might be a reason for the inefficient production of infectious viruses.
      Second, we generated a mutant recombinant virus, rMG96A, which possesses an Ala-
      >Thr mutation at residue 24 of the M1 protein, a substitution demonstrated to be
      involved in the morphology (filamentous or spherical) of the influenza C VLPs. As
      expected, rMG96A exhibited a spherical morphology, whereas recombinant wild-type
      of C/Ann Arbor/1/50, rWT, exhibited a mainly filamentous morphology. Membrane
      flotation analysis of the cells infected with rWT or rMG96A revealed a difference
      in the ratio of membrane-associated M1 proteins, suggesting that the affinity of
      M1 protein to the cell membrane is a determinant for virion morphology.

PMID- 17537858
TI  - Direct interactions of Kaposi's sarcoma-associated herpesvirus/human herpesvirus
      8 ORF50/Rta protein with the cellular protein octamer-1 and DNA are critical for
      specifying transactivation of a delayed-early promoter and stimulating viral
      reactivation.
AB  - The Kaposi's sarcoma-associated herpesvirus (KSHV) delayed-early K-bZIP promoter
      contains an ORF50/Rta binding site whose sequence is conserved with the ORF57
      promoter. Mutation of the site in the full-length K-bZIP promoter reduced Rta
      mediated transactivation by greater than 80%. The K-bZIP element contains an
      octamer (Oct) binding site that overlaps the Rta site and is well conserved with
      Oct elements found in the immediate-early promoters of herpes simplex virus type
      1(HSV-1). The cellular protein Oct-1, but not Oct-2, binds to the K-bZIP element
      in a sequence-specific fashion in vitro and in vivo and stimulates Rta binding to
      the promoter DNA. The coexpression of Oct-1 enhances Rta-mediated transactivation
      of the wild type but not the mutant K-bZIP promoter, and Oct-1 and Rta proteins
      bind to each other directly in vitro. Mutations of Rta within an amino acid
      sequence conserved with HSV-1 virion protein 16 eliminate Rta's interactions with
      Oct-1 and K-bZIP promoter DNA but not RBP-Jk. The binding of Rta to both Oct-1
      and DNA contributes to the transactivation of the K-bZIP promoter and viral
      reactivation, and Rta mutants deficient for both interactions are completely
      debilitated. Our data suggest that the Rta/Oct-1 interaction is essential for
      optimal KSHV reactivation. Transfections of mouse embryo fibroblasts and an
      endothelial cell line suggest cell-specific differences in the requirement for
      Oct-1 or RBP-Jk in Rta-mediated transactivation of the K-bZIP promoter. We
      propose a model in which Rta transactivation of the promoter is specified by the
      combination of DNA binding and interactions with several cellular DNA binding
      proteins including Oct-1.

PMID- 17537860
TI  - Coreceptor switch in R5-tropic simian/human immunodeficiency virus-infected
      macaques.
AB  - The basis for the switch from CCR5 to CXCR4 coreceptor usage seen in
      approximately 50% of human immunodeficiency virus type 1 (HIV-1) subtype B
      infected individuals as disease advances is not well understood. Among the
      reasons proposed are target cell limitation and better immune recognition of the
      CXCR4 (X4)-tropic compared to the CCR5 (R5)-tropic virus. We document here X4
      virus emergence in a rhesus macaque (RM) infected with R5-tropic simian/human
      immunodeficiency virus, demonstrating that coreceptor switch can happen in a
      nonhuman primate model of HIV/AIDS. The switch to CXCR4 usage in RM requires
      envelope sequence changes in the V3 loop that are similar to those found in
      humans, suggesting that the R5-to-X4 evolution pathways in the two hosts overlap.
      Interestingly, compared to the inoculating R5 virus, the emerging CXCR4-using
      virus is highly neutralization sensitive. This finding, coupled with the
      observation of X4 evolution and appearance in an animal with undetectable
      circulating virus-specific antibody and low cellular immune responses, lends
      further support to an inhibitory role of antiviral immunity in HIV-1 coreceptor
      switch.

PMID- 17537861
TI  - Genetic adaptation to untranslated region-mediated enterovirus growth deficits by
      mutations in the nonstructural proteins 3AB and 3CD.
AB  - Both untranslated regions (UTRs) of plus-strand RNA virus genomes jointly control
      translation and replication of viral genomes. In the case of the Enterovirus
      genus of the Picornaviridae family, the 5'UTR consists of a cloverleaf-like
      terminus preceding the internal ribosomal entry site (IRES) and the 3' terminus
      is composed of a structured 3'UTR and poly(A). The IRES and poly(A) have been
      implicated in translation control, and all UTR structures, in addition to cis
      acting genetic elements mapping to the open reading frame, have been assigned
      roles in RNA replication. Viral UTRs are recognized by viral and host cell RNA
      binding proteins that may co-determine genome stability, translation, plus- and
      minus-strand RNA replication, and scaffolding of viral replication complexes
      within host cell substructures. In this report, we describe experiments with
      coxsackie B viruses with a cell type-specific propagation deficit in Sk-N-Mc
      neuroblastoma cells conferred by the combination of a heterologous IRES and
      altered 3'UTR. Serial passage of these constructs in Sk-N-Mc cells yielded
      genetic adaptation by mutations within the viral nonstructural proteins 3A and
      3C. Our data implicate 3A and/or 3C or their precursors 3AB and/or 3CD in a
      functional complex with the IRES and 3'UTR that drives viral propagation.
      Adaptation to neuroblastoma cells suggests an involvement of cell type-specific
      host factors or the host cell cytoplasmic milieu in this phenomenon.

PMID- 17537862
TI  - Monitoring the antiviral effect of alpha interferon on individual cells.
AB  - An infectious hepatitis C virus (HCV) cDNA clone (JFH1) was generated recently.
      However, quantitative analysis of HCV infection and observation of infected cells
      have proved to be difficult because the yield of HCV in cell cultures is fairly
      low. We generated infectious HCV clones containing the convenient reporters green
      fluorescent protein (GFP) and Renilla luciferase in the NS5a-coding sequence. The
      new viruses responded to antiviral agents in a dose-dependent manner. Responses
      of individual cells containing HCV to alpha interferon (IFN-alpha) were monitored
      using GFP-tagged HCV and time-lapse confocal microscopy. Marked variations in the
      response to IFN-alpha were observed among HCV-containing cells.

PMID- 17537863
TI  - Mn2+ suppressor mutations and biochemical communication between Ty1 reverse
      transcriptase and RNase H domains.
AB  - Ty1 reverse transcriptase/RNase H (RT/RH) is exquisitely sensitive to manganese
      concentrations. Elevated intracellular free Mn(2+) inhibits Ty1
      retrotransposition and in vitro Ty1 RT-polymerizing activity. Furthermore, Mn(2+)
      inhibition is not limited to the Ty1 RT, as this ion similarly inhibits the
      activities of both avian myeloblastosis virus and human immunodeficiency virus
      type 1 RTs. To further characterize Mn(2+) inhibition, we generated RT/RH
      suppressor mutants capable of increased Ty1 transposition in pmr1 Delta cells.
      PMR1 codes for a P-type ATPase that regulates intracellular calcium and manganese
      ion homeostasis, and pmr1 mutants accumulate elevated intracellular manganese
      levels and display 100-fold less transposition than PMR1(+) cells. Mapping of
      these suppressor mutations revealed, surprisingly, that suppressor point
      mutations localize not to the RT itself but to the RH domain of the protein.
      Furthermore, Mn(2+) inhibition of in vitro RT activity is greatly reduced in all
      the suppressor mutants, whereas RH activity and cleavage specificity remain
      largely unchanged. These intriguing results reveal that the effect of these
      suppressor mutations is transmitted to the polymerase domain and suggest
      biochemical communication between these two domains during reverse transcription.

PMID- 17537864
TI  - Natural recombination event within the capsid genomic region leading to a
      chimeric strain of human enterovirus B.
AB  - Recombination between two strains is a known phenomenon for enteroviruses
      replicating within a single cell. We describe a recombinant strain recovered from
      human stools, typed as coxsackievirus B4 (CV-B4) and CV-B3 after partial
      sequencing of the VP1 and VP2 coding regions, respectively. The strain was
      neutralized by a polyclonal CV-B3-specific antiserum but not by a CV-B4-specific
      antiserum. The nucleotide sequence analysis of the whole structural genomic
      region showed the occurrence of a recombination event at position 1950 within the
      VP3 capsid gene, in a region coding for the 2b antigenic site previously
      described for CV-B3. This observation evidences for the first time the occurrence
      of an interserotypic recombination within the VP2-VP3-VP1 capsid region between
      two nonpoliovirus enterovirus strains. The neutralization pattern suggests that
      the major antigenic site is located within the VP2 protein.

PMID- 17537865
TI  - X-ray crystal structures of human immunodeficiency virus type 1 protease mutants
      complexed with atazanavir.
AB  - Atazanavir, which is marketed as REYATAZ, is the first human immunodeficiency
      virus type 1 (HIV-1) protease inhibitor approved for once-daily administration.
      As previously reported, atazanavir offers improved inhibitory profiles against
      several common variants of HIV-1 protease over those of the other peptidomimetic
      inhibitors currently on the market. This work describes the X-ray crystal
      structures of complexes of atazanavir with two HIV-1 protease variants, namely,
      (i) an enzyme optimized for resistance to autolysis and oxidation, referred to as
      the cleavage-resistant mutant (CRM); and (ii) the M46I/V82F/I84V/L90M mutant of
      the CRM enzyme, which is resistant to all approved HIV-1 protease inhibitors,
      referred to as the inhibitor-resistant mutant. In these two complexes, atazanavir
      adopts distinct bound conformations in response to the V82F substitution, which
      may explain why this substitution, at least in isolation, has yet to be selected
      in vitro or in the clinic. Because of its nearly symmetrical chemical structure,
      atazanavir is able to make several analogous contacts with each monomer of the
      biological dimer.

PMID- 17537866
TI  - Gemifloxacin once daily for 5 days versus 7 days for the treatment of community
      acquired pneumonia: a randomized, multicentre, double-blind study.
AB  - OBJECTIVES: Short-course therapy has been advocated for the treatment of
      community-acquired pneumonia (CAP). We compared the efficacy and safety of 5 and
      7 day courses of gemifloxacin for outpatient treatment of mild-moderate CAP.
      PATIENTS AND METHODS: In a multicentre, double-blind, parallel group study,
      patients were randomized to receive 320 mg of oral gemifloxacin once daily for 5
      or 7 days. Over 95% of all patients in each cohort had a Fine score of <or=III.
      The primary efficacy endpoint was clinical cure at follow-up (days 24-30).
      Secondary outcomes were clinical and bacteriological responses at the end of
      therapy (days 7-9) and bacteriological and radiological responses at follow-up.
      Adverse events (AEs) were also monitored. RESULTS: In a total of 469 per protocol
      (PP) patients, clinical resolution at follow-up was 95% and 92% for 5 and 7 day
      treatments, respectively [95% confidence interval (CI) -1.48, 7.42], indicating
      non-inferiority of 5 day treatment. Clinical resolution at the end of therapy was
      96% for both regimens (95% CI -3.85, 3.42). Bacteriological response rates in PP
      patients at the end of therapy were 94% and 96% for 5 and 7 day groups,
      respectively (95% CI -8.27, 3.25) and 91% for both groups at follow-up (95% CI 
      6.89, 7.93). Radiological success in PP patients at follow-up was 98% and 93% in
      5 and 7 day groups, respectively (95% CI 0.35, 7.91). Pre-therapy pathogens were
      identified in 242 (47.3%) patients, most commonly Streptococcus pneumoniae.
      Frequency of treatment-related AEs was 21% in both cohorts with discontinuation
      rates of 1.2% and 2% in the 5 and 7 day groups, respectively. A lower incidence
      of rash was observed in the 5 day cohort (0.4%) versus the 7 day cohort (2.8%)
      (P=0.04). CONCLUSIONS: Gemifloxacin once daily for 5 days is not inferior to 7
      days in the PP population with respect to clinical, bacteriological and
      radiological efficacy. Further work is needed, however, to explore whether fewer
      treatment days would improve patient compliance and reduce the incidence of AEs.

PMID- 17537868
TI  - Amphotericin B deoxycholate: no significant advantage of a 24 h over a 6 h
      infusion schedule.

PMID- 17537869
TI  - Metabolism, excretion, and pharmacokinetics of [14C]tigecycline, a first-in-class
      glycylcycline antibiotic, after intravenous infusion to healthy male subjects.
AB  - Tigecycline, a novel, first-in-class glycylcycline antibiotic, has been approved
      for the treatment of complicated intra-abdominal infections and complicated skin
      and skin structure infections. The pharmacokinetics, metabolism, and excretion of
      [(14)C]tigecycline were examined in healthy male volunteers. Tigecycline has been
      shown to bind to bone; thus, to minimize the amount of radioactivity binding to
      bone and to maximize the recovery of radioactivity, tigecycline was administered
      intravenously (30-min infusion) as a single 100-mg dose, followed by six 50-mg
      doses, every 12 h, with the last dose being [(14)C]tigecycline (50 microCi).
      After the final dose, the pharmacokinetics of tigecycline in serum showed a long
      half-life (55.8 h) and a large volume of distribution (21.0 l/kg), whereas
      radioactivity in serum had a shorter half-life (6.9 h) and a smaller volume of
      distribution (3.3 l/kg). The major route of elimination was feces, containing 59%
      of the radioactive dose, whereas urine contained 32%. Unchanged tigecycline was
      the predominant drug-related compound in serum, urine, and feces. The major
      metabolic pathways identified were glucuronidation of tigecycline and amide
      hydrolysis followed by N-acetylation to form N-acetyl-9-aminominocycline. The
      glucuronide metabolites accounted for 5 to 20% of serum radioactivity, and
      approximately 9% of the dose was excreted as glucuronide conjugates within 48 h.
      Concentrations of N-acetyl-9-aminominocycline were approximately 6.5% and 11% of
      the tigecycline concentrations in serum and urine, respectively. Excretion of
      unchanged tigecycline into feces was the primary route of elimination, and the
      secondary elimination pathways were renal excretion of unchanged drug and
      metabolism to glucuronide conjugates and N-acetyl-9-aminominocycline.

PMID- 17537870
TI  - Hepatic metabolism of MK-0457, a potent aurora kinase inhibitor: interspecies
      comparison and role of human cytochrome P450 and flavin-containing monooxygenase.
AB  - MK-0457 (N-[4([4-(4-methylpiperazin-1-yl)-6-[(3-methyl-1H-pyrazol-5 
      yl)amino]pyrimidin-2-yl]thio)phenyl]cyclopropanecarboxamide), an Aurora kinase
      inhibitor in development for the treatment of cancer, was evaluated for its in
      vitro metabolism in different species. This compound primarily underwent N
      oxidation and N-demethylation in human, monkey, dog, and rat liver preparations.
      However, N-demethylation was less significant in dogs. The formation of minor
      metabolites varied with species, but all metabolites generated in human
      hepatocytes were observed in animals. Results of immunoinhibition, selective
      chemical inhibition, thermal inactivation, and metabolism by recombinant
      cytochromes P450 and flavin-containing monoogygenases (FMOs) strongly suggest
      that CYP3A4 and FMO3 comparably contributed to MK-0457 N-oxidation in human liver
      microsomes, where the reaction conformed to Michaelis-Menten kinetics. These
      studies indicate a major role of CYP2C8 in the N-demethylation reaction, whereas
      CYP3A4 only made a minor contribution. However, significant substrate inhibition
      was observed with MK-0457 N-demethylation at high substrate concentrations (>10
      microM) in human liver microsomes relative to the anticipated therapeutic
      exposure. A multienzyme metabolic pathway such as this may mitigate the potential
      of drug interactions in clinical treatment with MK-0457.

PMID- 17537871
TI  - Involvement of up-regulation of hepatic breast cancer resistance protein in
      decreased plasma concentration of 7-ethyl-10-hydroxycamptothecin (SN-38) by
      coadministration of S-1 in rats.
AB  - The safety and efficacy of combination therapy with 7-ethyl-10-[4-[1-piperidino]
      1-piperidino]carbonyloxycamptothecin (CPT-11, irinotecan) and S-1 composed of
      tegafur, a prodrug of 5-fluorouracil, gimeracil, and potassium oxonate, have been
      confirmed in patients with colorectal cancer. Previously, we showed that p.o.
      coadministration of S-1 decreased the plasma concentration of both CPT-11 and its
      metabolites in a patient with advanced colorectal cancer. The aim of this study
      was to clarify the mechanism of drug interaction using both in vivo and in vitro
      methods. Rats were administered S-1 p.o. (10 mg/kg) once a day for 7 consecutive
      days. On day 7, CPT-11 (10 mg/kg) was administered by i.v. injection.
      Coadministration of S-1 affected the pharmacokinetic behavior of CPT-11 and its
      metabolites, with a decrease in the C(max) and area under the plasma
      concentration curve (AUC) of the active metabolite 7-ethyl-10-hydroxycampothecin
      (SN-38) lactone form. Furthermore, the rate of biliary excretion of the SN-38
      carboxylate form increased on coadministration of S-1. In the liver, the level of
      breast cancer resistance protein (BCRP), but not P-glycoprotein and multidrug
      resistance-associated protein 2, was elevated after administration of S-1.
      Enzymatic conversion of CPT-11 to SN-38 by carboxylesterase (CES) was unaffected
      by the liver microsomes of rats treated with S-1. In addition, components of S-1
      did not inhibit the hydrolysis of p-nitrophenylacetate, a substrate of CES, in
      the S9 fraction of HepG2 cells. Therefore, the mechanism of drug interaction
      between CPT-11 and S-1 appears to involve up-regulation of BCRP in the liver,
      resulting in an increased rate of biliary excretion of SN-38 accompanied by a
      decrease in the C(max) and AUC of SN-38.

PMID- 17537872
TI  - Computational approaches that predict metabolic intermediate complex formation
      with CYP3A4 (+b5).
AB  - Some mechanism-based inhibitors cause irreversible inhibition by forming a
      metabolic intermediate complex (MIC) with cytochrome P450. In the present study,
      54 molecules (substrates of CYP3A and amine-containing compounds that are not
      known substrates of CYP3A) were spectrophotometrically assessed for their
      propensity to cause MIC formation with recombinant CYP3A4 (+b(5)). Comparisons of
      common physicochemical properties showed that mean (+/-S.D.) mol. wt. of MIC
      forming compounds was significantly greater than mean mol. wt. of non-MIC-forming
      compounds, 472 (+/-173) versus 307 (+/-137), respectively. Computational
      pharmacophores, logistic regression, and recursive partitioning (RP) approaches
      were applied to predict MIC formation from molecular structure and to generate a
      quantitative structure activity relationship. A pharmacophore built with SKF-525A
      (2-diethylaminoethyl 2:2-diphenylvalerate hydrochloride), erythromycin,
      amprenavir, and norverapamil indicated that four hydrophobic features and a
      hydrogen bond acceptor were important for these MIC-forming compounds. Two
      different RP methods using either simple descriptors or 2D augmented atom
      descriptors indicated that hydro-phobic and hydrogen bond acceptor features were
      required for MIC formation. Both of these RP methods correctly predicted the MIC
      formation status with CYP3A4 for 10 of 12 literature molecules in an independent
      test set. Logistic multiple regression and a third classification tree model
      predicted 11 of 12 molecules correctly. Both models possessed a hydrogen bond
      acceptor and represent an approach for predicting CYP3A4 MIC formation that can
      be improved using more data and molecular descriptors. The preliminary
      pharmacophores provide structural insights that complement those for CYP3A4
      inhibitors and substrates.

PMID- 17537873
TI  - ABCG2 (breast cancer resistance protein/mitoxantrone resistance-associated
      protein) ATPase assay: a useful tool to detect drug-transporter interactions.
AB  - The ATPase assay using membrane preparations from recombinant baculovirus
      infected Spodoptera frugiperda ovarian (Sf9) cells is widely used to detect the
      interaction of compounds with different ATP-binding cassette transporters.
      However, Sf9 membrane preparations containing the wild-type ABCG2 transporter
      show an elevated baseline vanadate-sensitive ATPase activity, which cannot be
      further stimulated by substrates of ABCG2. Therefore, this assay system cannot be
      used for the detection of ABCG2 substrates. To overcome this difficulty we 1)
      purified membranes from a selected human cell line expressing wild-type ABCG2,
      and 2) inhibited the baseline ATPase activity with different inhibitors. In our
      modified assay, ABCG2 substrates were able to stimulate the baseline ATPase
      activity of ABCG2 expressed in membranes of human cells. Furthermore, using the
      specific ABCG2 inhibitors Ko143 or Ko134 allowed us to suppress the baseline
      vanadate-sensitive ATPase activity. Substrates of ABCG2 could stimulate this
      suppressed baseline ATPase, resulting in a better signal-to-background ratio and
      a robust assay to detect substrates of the ABCG2 transporter. The ATPase assay
      and the direct vesicular transport measurements for estrone-3-sulfate were in
      good accordance.

PMID- 17537874
TI  - Preparation and in vivo evaluation of a water-soluble prodrug for 2R-gamma
      tocotrienol and as a two-step prodrug for 2,7,8-trimethyl-2S-(beta-carboxyethyl)
      6-hydroxychroman (S-gamma-CEHC) in rat.
AB  - 2R-gamma-Tocotrienol (gamma-T3) is currently receiving attention because it has
      beneficial effects not observed with alpha-tocopherol. To achieve the effective
      delivery of gamma-T3, we synthesized three kinds of ester derivatives of gamma-T3
      and evaluated their use as hydrophilic prodrugs for gamma-T3 in vitro and in
      vivo. 2R-gamma-Tocotrienyl N,N-dimethylamino-acetate hydrochloride (compound 3)
      was a solid compound, with high solubility and stability in water, and was
      converted to gamma-T3 by esterases in rat and human liver. Intravenous
      administration of 3 in rats led to a rapid increase in the plasma, liver, heart,
      and kidney levels of gamma-T3. The bioavailability (plasma level) after
      intravenous administration was 82.5 +/- 13.4% and 100 +/- 11.3% for 3 and gamma
      T3 in surfactant, respectively, and the availability in liver was 213 +/- 47.6%
      and 100 +/- 4.8% for 3 and gamma-T3 in surfactant, respectively. Furthermore, the
      systemic availability of 2,7,8-trimethyl-2S-(beta-carboxyethyl)-6-hydroxychroman
      (S-gamma-CEHC), a metabolite of gamma-T3, was 78.6% for compound 3, 47.1% for
      gamma-T3 in surfactant, and 100% for racemic gamma-CEHC. Based on these results,
      we identified compound 3 as the most promising water-soluble prodrug of gamma-T3
      and two-step prodrug of S-gamma-CEHC.

PMID- 17537875
TI  - A minimal physiological model of thiopental distribution kinetics based on a
      multiple indicator approach.
AB  - Currently available models of thiopental disposition kinetics using only plasma
      concentration-time data neglect the influence of intratissue diffusion and
      provide no direct information on tissue partitioning in individual subjects. Our
      approach was based on a lumped-organ recirculatory model that has recently been
      applied to unbound compounds. The goal was to find the simplest model that
      accounts for the heterogeneity in tissue partition coefficients and accurately
      describes initial distribution kinetics of thiopental in dogs. To ensure
      identifiability of the underlying axially distributed capillary-tissue exchange
      model, simultaneously measured disposition data of the vascular indicator,
      indocyanine green, and the marker of whole body water, antipyrine, were analyzed
      together with those of thiopental. A model obtained by grouping the systemic
      organs in two subsystems containing fat and nonfat tissues, successfully
      described all data and allowed an accurate estimation of model parameters. The
      estimated tissue partition coefficients were in accordance with those measured in
      rats. Because of the effect of tissue binding, the diffusional equilibration time
      characterizing intratissue distribution of thiopental is longer than that of
      antipyrine. The approach could potentially be used in clinical pharmacokinetics
      and could increase our understanding of the effect of obesity on the disposition
      kinetics of lipid-soluble drugs.

PMID- 17537876
TI  - Characterization of benidipine and its enantiomers' metabolism by human liver
      cytochrome P450 enzymes.
AB  - Benidipine is a dihydropyridine calcium antagonist that has been used clinically
      as an antihypertensive and antianginal agent. It is used clinically as a
      racemate, containing the (-)-alpha and (+)-alpha isomers of benidipine. This
      study was performed to elucidate the metabolism of benidipine and its enantiomers
      in human liver microsomes (HLMs) and to characterize the cytochrome P450 (P450)
      enzymes that are involved in the metabolism of benidipine. Human liver microsomal
      incubation of benidipine in the presence of NADPH resulted in the formation of
      two metabolites, N-desbenzylbenidipine and dehydrobenidipine. The intrinsic
      clearance (CL(int)) of the formation of N-desbenzylbenidipine and
      dehydrobenidipine metabolites from (-)-alpha isomer was similar to those from the
      (+)-alpha isomer (1.9 +/- 0.1 versus 2.3 +/- 2.3 microl/min/pmol P450 and 0.5 +/-
      0.2 versus 0.6 +/- 0.6 microl/min/pmol P450, respectively). Correlation analysis
      between the known P450 enzyme activities and the rate of the formation of
      benidipine metabolites in the 15 HLMs showed that benidipine metabolism is
      correlated with CYP3A activity. The P450 isoform-selective inhibition study in
      liver microsomes and the incubation study of cDNA-expressed enzymes also showed
      that theN-debenzylation and dehydrogenation of benidipine are mainly mediated by
      CYP3A4 and CYP3A5. The total CL(int) values of CYP3A4-mediated metabolite
      formation from (-)-alpha isomer were similar to those from (+)-alpha isomer (17.7
      versus 14.4 microl/min/pmol P450, respectively). The total CL(int) values of
      CYP3A5-mediated metabolite formation from (-)-alpha isomer were also similar to
      those from (+)-alpha isomer (8.3 versus 11.0 microl/min/pmol P450, respectively).
      These findings suggest that CYP3A4 and CYP3A5 isoforms are major enzymes
      contributing to the disposition of benidipine, but stereoselective disposition of
      benidipine in vivo may be influenced not by stereoselective metabolism but by
      other factors.

PMID- 17537877
TI  - Improving journal club presentations, or, I can present that paper in under 10
      minutes.

PMID- 17537878
TI  - Continuing alendronate for an additional 5 years maintained bone mineral density
      in postmenopausal women.

PMID- 17537879
TI  - Annual mammographic screening beginning at 40 years of age did not significantly
      reduce breast cancer mortality after 10 years in women.

PMID- 17537880
TI  - Review: SSRIs lead to improvement in depression by the end of the first week.

PMID- 17537881
TI  - Self management plus usual care was more effective than usual care alone for
      lower urinary tract symptoms in men.

PMID- 17537882
TI  - Review: diacerein is more effective than placebo and is as effective as NSAIDs
      for knee and hip osteoarthritis.

PMID- 17537883
TI  - Review: inhaled corticosteroids reduce hospital admission and increase discharge
      rate during the first 4 hours in the emergency department for acute asthma.

PMID- 17537884
TI  - Review: the current evidence does not suggest that oral contraceptives hasten
      resolution of functional ovarian cysts.

PMID- 17537885
TI  - Etomidate had shorter induction and recovery times than midazolam for fracture
      reduction.

PMID- 17537886
TI  - Herbal supplements did not relieve vasomotor symptoms of menopause in women.

PMID- 17537887
TI  - Review: prokinetics, histamine H2 receptor antagonists, antimuscarinics, and
      proton pump inhibitors improve global symptoms in non-ulcer dyspepsia.

PMID- 17537888
TI  - Prompt insertion of tympanostomy tubes in infants and toddlers with persistent
      middle ear effusion did not improve developmental outcomes at 9-11 years of age.

PMID- 17537889
TI  - Encouraging influenza vaccination for nursing home staff reduced mortality and
      influenza like illness in the residents.

PMID- 17537890
TI  - Review: LABAs are better than leukotriene receptor antagonists when added to
      inhaled corticosteroids in recurrent asthma.

PMID- 17537891
TI  - Daily folic acid supplementation for 3 years improved cognitive function in older
      persons.

PMID- 17537892
TI  - Review: eradication therapy supplemented by probiotics increased eradication
      rates and reduced side effects in H pylori infection.

PMID- 17537893
TI  - After midtrimester amniocentesis the risk of spontaneous pregnancy loss was 6 per
      10,000.

PMID- 17537894
TI  - Collaborative care for depression in patients with diabetes increased depression
      free days and had economic benefit.

PMID- 17537895
TI  - Review: Framingham risk scores have variable accuracy in predicting CVD events in
      different patient populations.

PMID- 17537896
TI  - The ABCD, California, and unified ABCD2 risk scores predicted stroke within 2, 7,
      and 90 days after TIA.

PMID- 17537897
TI  - The Manchester Self Harm Rule had good sensitivity but poor specificity for
      predicting repeat self harm or suicide.

PMID- 17537898
TI  - How should clinicians interpret results reflecting the effect of an intervention
      on composite end points?

PMID- 17537899
TI  - Viral infections need to be excluded from the cohort for the results to be truly
      meaningful.

PMID- 17537900
TI  - Neuronal firing rates and patterns in the globus pallidus internus of patients
      with cervical dystonia differ from those with Parkinson's disease.
AB  - Cervical dystonia (CD) is a movement disorder that involves involuntary turning
      and twisting of the neck caused by abnormal muscle contraction. Deep brain
      stimulation (DBS) in the globus pallidus internus (GPi) is used to treat both CD
      and the motor symptoms of Parkinson's disease (PD). It has been suggested that
      the differing motor symptoms in CD and PD may arise from a decreased GPi output
      in CD and elevation of output in PD. To test this hypothesis, extracellular
      recordings of GPi neuronal activity were obtained during stereotactic surgery for
      the implantation of DBS electrodes in seven idiopathic CD and 14 PD patients. The
      mean GPi neuronal firing rate recorded from CD patients was lower than that in PD
      patients (P < 0.001; means +/- SE: 71.4 +/- 2.2 and 91.7 +/- 3.0 Hz,
      respectively). Furthermore, GPi neurons fired in a more irregular pattern
      consisting of more frequent and longer pauses in CD compared with PD patients.
      When comparisons were done based on locations of recordings, these differences in
      firing rates and patterns were limited to the ventral portion of the GPi. In
      contrast, no difference in firing rate or pattern was observed in the globus
      pallidus externus between the two groups. These findings suggest that alterations
      in both firing rate and firing pattern may underlie the differing motor symptoms
      associated with these two movement disorders.

PMID- 17537901
TI  - Complex cells increase their phase sensitivity at low contrasts and following
      adaptation.
AB  - One of the best-known dichotomies in neuroscience is the division of neurons in
      the mammalian primary visual cortex into simple and complex cells. Simple cells
      have receptive fields with separate on and off subregions and give phase
      sensitive responses to moving gratings, whereas complex cells have uniform
      receptive fields and are phase invariant. The phase sensitivity of a cell is
      calculated as the ratio of the first Fourier coefficient (F1) to the mean time
      average (Fo) of the response to moving sinusoidal gratings at 100% contrast.
      Cells are then classified as simple (F1/Fo >1) or complex (F1/Fo <1). We
      manipulated cell responses by changing the stimulus contrast or through
      adaptation. The F(1)/F(0) ratios of cells defined as complex at 100% contrast
      increased at low contrasts and following adaptation. Conversely, the F1/Fo ratios
      remained constant for cells defined as simple at 100% contrast. The latter cell
      type was primarily located in thalamorecipient layers 4 and 6. Many cells
      initially classified as complex exhibit F1/Fo >1 at low contrasts and after
      adaptation (particularly in layer 4). The results are consistent with the spike
      threshold hypothesis, which suggests that the division of cells into two types
      arises from the nonlinear interaction of spike threshold with membrane potential
      responses.

PMID- 17537902
TI  - Differential expression of intrinsic membrane currents in defined cell types of
      the anterolateral bed nucleus of the stria terminalis.
AB  - The anterolateral group of the bed nucleus of the stria terminalis (BNST(ALG))
      plays a critical role in a diverse array of behaviors, although little is known
      of the physiological properties of neurons in this region. Using whole cell patch
      clamp recordings from rat BNST(ALG) slices in vitro, we describe three distinct
      physiological cell types. Type I neurons were characterized by the presence of a
      depolarizing sag in response to hyperpolarizing current injection that resembled
      activation of the hyperpolarization-activated cation current I(h) and a regular
      firing pattern in response to depolarizing current injection. Type II neurons
      exhibited the same depolarizing sag in response to hyperpolarizing current
      injection, but burst-fired in response to depolarizing current injection, which
      was indicative of the activation of the low-threshold calcium current I(T). Type
      III neurons did not exhibit a depolarizing sag in response to hyperpolarizing
      current injection, but instead exhibited a fast time-independent rectification
      that became more pronounced with increased amplitude of hyperpolarizing current
      injection, and was indicative of activation of the inwardly rectifying potassium
      current I(K(IR)). Type III neurons also exhibited a regular firing pattern in
      response to depolarizing current. Using voltage-clamp analysis we further
      characterized the primary active currents that shaped the physiological
      properties of these distinct cell types, including I(h), I(T), I(K(IR)), the
      voltage-dependent potassium current I(A), and the persistent sodium current
      I(NaP). The functional relevance of each cell type is discussed in relation to
      prior anatomical studies, as well as how these currents may interact to modulate
      neuronal activity within the BNST(ALG).

PMID- 17537903
TI  - Biphasic modulation of GABA release from stellate cells by glutamatergic receptor
      subtypes.
AB  - The release of inhibitory transmitters from CNS neurons can be modulated by
      ionotropic glutamate receptors that are present in the presynaptic terminals. In
      the cerebellum, glutamate released from climbing fibers (but not from parallel
      fibers) activates presynaptic AMPA receptors and suppresses the release of the
      inhibitory transmitter GABA from basket cells onto postsynaptic Purkinje cells.
      This input-specific modulation has been attributed to the close proximity of the
      climbing fibers to the axons of the basket cells. Our recent work indicates that
      glutamate released from parallel fibers can "spill over" and reach the axons of
      stellate cells. Here I test the possibility that this spillover glutamate can
      activate presynaptic AMPA receptors in stellate cells and in this way modulate
      their release of GABA. I find that stimulation of parallel fibers activates AMPA
      receptors and transiently suppresses autoreceptor and autaptic GABAergic currents
      in stellate cells. Activation of AMPA receptors reduces the release of GABA and
      the suppression occurs more frequently in immature cells that have a high release
      probability. By contrast the release of GABA from mature stellate cells that have
      a low release probability is potentiated by the activation of NMDA-type glutamate
      receptors on presynaptic terminals. Thus during development, the glutamatergic
      modulation of GABA release switches from an AMPA-receptor-mediated transient
      suppression to a NMDA-receptor-induced lasting potentiation.

PMID- 17537904
TI  - Comparison of saccade-associated neuronal activity in the primate central
      mesencephalic and paramedian pontine reticular formations.
AB  - The oculomotor system must convert signals representing the target of an intended
      eye movement into appropriate input to drive the individual extraocular muscles.
      Neural models propose that this transformation may involve either a decomposition
      of the intended eye displacement signal into horizontal and vertical components
      or an implicit process whereby component signals do not predominate until the
      level of the motor neurons. Thus decomposition models predict that premotor
      neurons should primarily encode component signals while implicit models predict
      encoding of off-cardinal optimal directions by premotor neurons. The central
      mesencephalic reticular formation (cMRF) and paramedian pontine reticular
      formation (PPRF) are two brain stem regions that likely participate in the
      development of motor activity since both structures are anatomically connected to
      nuclei that encode movement goal (superior colliculus) and generate horizontal
      eye movements (abducens nucleus). We compared cMRF and PPRF neurons and found
      they had similar relationships to saccade dynamics, latencies, and movement
      fields. Typically, the direction preference of these premotor neurons was
      horizontal, suggesting they were related to saccade components. To confirm this
      supposition, we studied the neurons during a series of oblique saccades that
      caused "component stretching" and thus allowed the vectorial (overall) saccade
      velocity to be dissociated from horizontal component velocity. The majority of
      cMRF and PPRF neurons encoded component velocity across all saccades, supporting
      decomposition models that suggest horizontal and vertical signals are generated
      before the level of the motoneurons. However, we also found novel vectorial eye
      velocity encoding neurons that may have important implications for saccade
      control.

PMID- 17537905
TI  - Physiological properties of mouse skin sensory neurons recorded intracellularly
      in vivo: temperature effects on somal membrane properties.
AB  - Recent combined analyses of the structural, functional, and molecular attributes
      of individual skin sensory neurons using semi-intact in vitro preparations from
      mice have provided a wealth of novel insights into nociceptor biology. How these
      findings translate to more natural conditions nevertheless remains unresolved.
      Toward this end, intracellular recordings were obtained from 362 physiologically
      identified dorsal root ganglion (DRG) neurons in a new in vivo mouse preparation
      developed for combined structure/function analyses of individual skin sensory
      neurons. Recordings were conducted at thoracic levels in adult decorticate mice
      for comparison with in vitro findings from the same trunk region. In all, 270
      neurons were recorded at DRG temperatures tightly regulated at normal core values
      to establish a baseline and 137 skin sensory neurons were included in detailed
      analyses of somal properties for comparisons with similar data obtained under
      reduced temperatures mirroring in vitro conditions. Recovery of Neurobiotin
      labeled central projections was crucial for verifying perceived afferent identity
      of certain neurons. Further, profound temperature dependency was seen across
      diverse physiological properties. Indeed, the broad, inflected somal spikes
      normally viewed as diagnostic of myelinated nociceptors were found to be a
      product of reduced temperatures and were not present at normal core values.
      Moreover, greater complexity was observed peripherally in the mechanical and
      thermal sensitivity profile of nociceptive and nonnociceptive populations than
      that seen under in vitro conditions. This novel in vivo preparation therefore
      holds considerable promise for future analyses of nociceptor function and
      plasticity in normal and transgenic models of pain mechanisms.

PMID- 17537906
TI  - "Heterosynaptic" LTD in the dentate gyrus of anesthetized rat requires
      homosynaptic activity.
AB  - Heterosynaptic long-term depression (LTD) is conventionally defined as occurring
      at synapses that are inactive during a time when neighboring synapses are
      activated by high-frequency stimulation. A new model that combines computational
      properties of both the Bienenstock, Cooper and Munro model and spike timing
      dependent plasticity, however, suggests that such LTD actually may require
      presynaptic activity in the depressed pathway. We tested experimentally whether
      presynaptic activity is in fact necessary for previously described heterosynaptic
      LTD in lateral perforant path synapses in the dentate gyrus of urethane
      anesthetized rats. As predicted by the model, procaine infusion into the lateral
      path fibers, sufficient to transiently block neural activity in this pathway,
      prevented the induction of LTD in the lateral path following medial path high
      frequency stimulation. These data indicate that the previously described
      heterosynaptic LTD in the dentate gyrus in vivo is actually a form of
      homosynaptic LTD, requiring presynaptic activity in the depressed pathway.

PMID- 17537907
TI  - Cortical and collicular inputs to cells in the rat paralaminar thalamic nuclei
      adjacent to the medial geniculate body.
AB  - The paralaminar nuclei, including the medial division of the medial geniculate
      nucleus, surround the auditory thalamus medially and ventrally. This multimodal
      area receives convergent inputs from auditory, visual, and somatosensory
      structures and sends divergent outputs to cortical layer 1, amygdala, basal
      ganglia, and elsewhere. Studies implicate this region in the modulation of
      cortical 40-Hz oscillations, cortical information binding, and the conditioned
      fear response. We recently showed that the basic anatomy and intrinsic physiology
      of paralaminar cells are unlike that of neurons elsewhere in sensory thalamus.
      Here we evaluate the synaptic inputs to paralaminar cells from the inferior and
      superior colliculi and the cortex. Combined physiological and anatomical evidence
      indicates that paralaminar cells receive both excitatory and inhibitory inputs
      from both colliculi and excitatory cortical inputs. Excitatory inputs from all
      three sources typically generate small summating EPSPs composed of AMPA and NMDA
      components and terminate primarily on smaller dendrites and occasionally on
      dendritic spines. The cortical input shows strong paired-pulse facilitation
      (PPF), whereas both collicular inputs show weak PPF or paired-pulse depression
      (PPD). EPSPs of cells with no low-threshold calcium conductance do not evoke a
      burst response when the cell is hyperpolarized. Longer-latency EPSPs were seen
      and our evidence indicates that these arise from axon collateral inputs of other
      synaptically activated paralaminar cells. The inhibitory collicular inputs are
      GABAergic, activate GABA(A) receptors, and terminate on dendrites. Their
      activation can greatly alter EPSP-generated spike number and timing.

PMID- 17537908
TI  - Role of sustained excitability of the leg motor cortex after transcranial
      magnetic stimulation in associative plasticity.
AB  - Changes in the strength of corticospinal projections to muscles in the upper and
      lower limbs are induced in conscious humans after paired associative stimulation
      (PAS) to the motor cortex. We tested whether an intervention of PAS consisting of
      90 low-frequency (0.1-Hz) stimuli to the common peroneal nerve combined with
      suprathreshold transcranial magnetic stimulation (TMS) produces specific changes
      to the motor-evoked potentials (MEPs) in lower leg muscles if the afferent volley
      from peripheral stimulation is timed to arrive at the motor cortex after TMS
      induced firing of corticospinal neurons. Unlike PAS in the hand, MEP facilitation
      in the leg was produced when sensory inputs were estimated to arrive at the motor
      cortex over a range of 15 to 90 ms after cortical stimulation. We examined
      whether this broad range of facilitation occurred as a result of prolonged
      subthreshold excitability of the motor cortex after a single pulse of
      suprathreshold TMS so that coincident excitation from sensory inputs arriving
      many milliseconds after TMS can occur. We found that significant facilitation of
      MEP responses (>200%) occurred when the motor cortex was conditioned with
      suprathreshold TMS tens of milliseconds earlier. Likewise, it was possible to
      induce strong MEP facilitation (85% at 60 min) when afferent inputs were directly
      paired with subthreshold TMS. We argue that in the leg motor cortex, facilitation
      of MEP responses from PAS occurred over a large range of interstimulus intervals
      as a result of the paired activation of sensory inputs with sustained,
      subthreshold activity of cortical neurons that follow a pulse of suprathreshold
      TMS.

PMID- 17537909
TI  - Neural control of superficial and deep neck muscles in humans.
AB  - Human neck muscles have a complex multi-layered architecture. The role and neural
      control of these neck muscles were examined in nine seated subjects performing
      three series of isometric neck muscle contractions: 50-N contractions in eight
      fixed horizontal directions, 25-N contractions, and 50-N contractions, both with
      a continuously changing horizontal force direction. Activity in the left
      sternocleidomastoid, trapezius, levator scapulae, splenius capitis, semispinalis
      capitis, semispinalis cervicis, and multifidus muscles was measured with wire
      electrodes inserted at the C(4)/C(5) level under ultrasound guidance. We
      hypothesized that deep and superficial neck muscles would function as postural
      and focal muscles, respectively, and would thus be controlled by different neural
      signals. To test these hypotheses, electromyographic (EMG) tuning curves and
      correlations in the temporal and frequency domains were computed. Three main
      results emerged from these analyses: EMG tuning curves from all muscles exhibited
      well-defined preferred directions of activation for the 50-N isometric forces,
      larger contractions (25 vs. 50 N) yielded more focused EMG tuning curves, and
      agonist neck muscles from all layers received a common neural drive in the range
      of 10-15 Hz. The current results demonstrate that all neck muscles can exhibit
      phasic activity during isometric neck muscle contractions. Similar oscillations
      in the EMG of neck muscles from different layers further suggest that neck
      motoneurons were activated by common neurons. The reticular formation appears a
      likely generator of the common drive to the neck motoneurons due to its
      widespread projections to different groups of neck motoneurons.

PMID- 17537910
TI  - Neuromuscular abnormalities associated with spasticity of upper extremity muscles
      in hemiparetic stroke.
AB  - Our objective was to assess the mechanical changes associated with spasticity in
      elbow muscles of chronic hemiparetic stroke survivors and to compare these
      changes with those recorded in the ankle muscles of a similar cohort. We first
      characterized elbow dynamic stiffness by applying pseudorandom binary positional
      perturbations to the joints at different initial angles, over the entire range of
      motion, with subjects relaxed. We separated this stiffness into intrinsic and
      reflex components using a novel parallel cascade system identification technique.
      In addition, for controls, we studied the nonparetic limbs of stroke survivors
      and limbs of age-matched healthy subjects as primary and secondary controls. We
      found that both reflex and intrinsic stiffnesses were significantly larger in the
      stroke than in the nonparetic elbow muscles, and the differences increased as the
      elbow was extended. Reflex stiffness increased monotonically with the elbow angle
      in both paretic and nonparetic sides. In contrast, the modulation of intrinsic
      stiffness with elbow position was different in nonparetic limbs; intrinsic
      stiffness decreased sharply from full- to mid-flexion in both sides, then it
      increased continuously with the elbow extension in the paretic side. It remained
      invariant in the nonparetic side. Surprisingly, reflex stiffness was larger in
      the nonparetic than in the normal control arm, yet intrinsic stiffness was
      smaller in the nonparetic arm. Finally, we compare the angular dependence of
      paretic elbow and ankle muscles and show that the modulation of reflex stiffness
      with position was strikingly different.

PMID- 17537911
TI  - Mesenchyme Forkhead 1 (FOXC2) plays a key role in metastasis and is associated
      with aggressive basal-like breast cancers.
AB  - The metastatic spread of epithelial cancer cells from the primary tumor to
      distant organs mimics the cell migrations that occur during embryogenesis. Using
      gene expression profiling, we have found that the FOXC2 transcription factor,
      which is involved in specifying mesenchymal cell fate during embryogenesis, is
      associated with the metastatic capabilities of cancer cells. FOXC2 expression is
      required for the ability of murine mammary carcinoma cells to metastasize to the
      lung, and overexpression of FOXC2 enhances the metastatic ability of mouse
      mammary carcinoma cells. We show that FOXC2 expression is induced in cells
      undergoing epithelial-mesenchymal transitions (EMTs) triggered by a number of
      signals, including TGF-beta1 and several EMT-inducing transcription factors, such
      as Snail, Twist, and Goosecoid. FOXC2 specifically promotes mesenchymal
      differentiation during an EMT and may serve as a key mediator to orchestrate the
      mesenchymal component of the EMT program. Expression of FOXC2 is significantly
      correlated with the highly aggressive basal-like subtype of human breast cancers.
      These observations indicate that FOXC2 plays a central role in promoting invasion
      and metastasis and that it may prove to be a highly specific molecular marker for
      human basal-like breast cancers.

PMID- 17537912
TI  - Comparative support for the niche variation hypothesis that more generalized
      populations also are more heterogeneous.
AB  - There is extensive evidence that some species of ecological generalists, which
      use a wide diversity of resources, are in fact heterogeneous collections of
      relatively specialized individuals. This within-population variation, or
      "individual specialization," is a key requirement for frequency-dependent
      interactions that may drive a variety of types of evolutionary diversification
      and may influence the population dynamics and ecological interactions of species.
      Consequently, it is important to understand when individual specialization is
      likely to be strong or weak. The niche variation hypothesis (NVH) suggests that
      populations tend to become more generalized when they are released from
      interspecific competition. This niche expansion was proposed to arise via
      increased variation among individuals rather than increased individual niche
      breadth. Consequently, we expect ecological generalists to exhibit stronger
      individual specialization, but this correlation has been repeatedly rejected by
      empiricists. The drawback with previous empirical tests of the NVH is that they
      use morphological variation as a proxy for niche variation, ignoring the role of
      behavior and complex phenotype-function relationships. Here, we used diet data to
      directly estimate niche variation among individuals. Consistent with the NVH, we
      show that more generalized populations also exhibit more niche variation. This
      trend is quite general, appearing in all five case studies examined: three-spine
      stickleback, Eurasian perch, Anolis lizards, intertidal gastropods, and a
      community of neotropical frogs. Our results suggest that generalist populations
      may tend to be more ecologically variable. Whether this translates into greater
      genetic variation, evolvability, or ecological stability remains to be
      determined.

PMID- 17537913
TI  - A genome-wide approach to identify genetic variants that contribute to etoposide
      induced cytotoxicity.
AB  - Large interindividual variance has been observed in sensitivity to drugs. To
      comprehensively decipher the genetic contribution to these variations in drug
      susceptibility, we present a genome-wide model using human lymphoblastoid cell
      lines from the International HapMap consortium, of which extensive genotypic
      information is available, to identify genetic variants that contribute to
      chemotherapeutic agent-induced cytotoxicity. Our model integrated genotype, gene
      expression, and sensitivity of HapMap cell lines to drugs. Cell lines derived
      from 30 trios of European descent (Center d'Etude du Polymorphisme Humain
      population) and 30 trios of African descent (Yoruban population) were used. Cell
      growth inhibition at increasing concentrations of etoposide for 72 h was
      determined by using alamarBlue assay. Gene expression on 176 HapMap cell lines
      (87 Center d'Etude du Polymorphisme Humain population and 89 Yoruban population)
      was determined by using the Affymetrix GeneChip Human Exon 1.0ST Array. We
      evaluated associations between genotype and cytotoxicity, genotype and gene
      expression and correlated gene expression of the identified candidates with
      cytotoxicity. The analysis identified 63 genetic variants that contribute to
      etoposide-induced toxicity through their effect on gene expression. These include
      genes that may play a role in cancer (AGPAT2, IL1B, and WNT5B) and genes not yet
      known to be associated with sensitivity to etoposide. This unbiased method can be
      used to elucidate genetic variants contributing to a wide range of cellular
      phenotypes induced by chemotherapeutic agents.

PMID- 17537914
TI  - Structural elucidation of the m157 mouse cytomegalovirus ligand for Ly49 natural
      killer cell receptors.
AB  - Natural killer (NK) cells express activating and inhibitory receptors that, in
      concert, survey cells for proper expression of cell surface major
      histocompatibility complex (MHC) class I molecules. The mouse cytomegalovirus
      encodes an MHC-like protein, m157, which is the only known viral antigen to date
      capable of engaging both activating (Ly49H) and inhibitory (Ly49I) NK cell
      receptors. We have determined the 3D structure of m157 and studied its
      biochemical and cellular interactions with the Ly49H and Ly49I receptors. m157
      has a characteristic MHC-fold, yet possesses several unique structural features
      not found in other MHC class I-like molecules. m157 does not bind peptides or
      other small ligands, nor does it associate with beta(2)-microglobulin. Instead,
      m157 engages in extensive intra- and intermolecular interactions within and
      between its domains to generate a compact minimal MHC-like molecule. m157's
      binding affinity for Ly49I (K(d) approximately 0.2 microM) is significantly
      higher than that of classical inhibitory Ly49-MHC interactions. Analysis of viral
      escape mutations on m157 that render it resistant to NK killing reveals that it
      is likely to be recognized by Ly49H in a binding mode that differs from Ly49/MHC
      I. In addition, Ly49H+ NK cells can efficiently lyse RMA cells expressing m157,
      despite the presence of native MHC class I. Collectively, our results show that
      m157 represents a structurally divergent form of MHC class I-like proteins that
      directly engage Ly49 receptors with appreciable affinity in a noncanonical
      fashion.

PMID- 17537915
TI  - Early cardiac development: a Wnt beat away.

PMID- 17537916
TI  - Juvenile hormone resistance gene Methoprene-tolerant controls entry into
      metamorphosis in the beetle Tribolium castaneum.
AB  - Besides being a spectacular developmental process, metamorphosis is key to insect
      success. Entry into metamorphosis is controlled by juvenile hormone (JH). In
      larvae, JH prevents pupal and adult morphogenesis, thus keeping the insect in its
      immature state. How JH signals to preclude metamorphosis is poorly understood,
      and a JH receptor remains unknown. One candidate for the JH receptor role is the
      Methoprene-tolerant (Met) Per-Arnt-Sim (PAS) domain protein [also called
      Resistance to JH, Rst (1)JH], whose loss confers tolerance to JH and its mimic
      methoprene in the fruit fly Drosophila melanogaster. However, Met deficiency does
      not affect the larval-pupal transition, possibly because this process does not
      require JH absence in Drosophila. By contrast, the red flour beetle Tribolium
      castaneum is sensitive to developmental regulation by JH, thus making an ideal
      system to examine the role of Met in the antimetamorphic JH action. Here we show
      that impaired function of the Met ortholog TcMet renders Tribolium resistant to
      the effects of ectopic JH and, in a striking contrast to Drosophila, causes early
      stage beetle larvae to undergo precocious metamorphosis. This is evident as TcMet
      deficient larvae pupate prematurely or develop specific heterochronic phenotypes
      such as pupal-like cuticular structures, appendages, and compound eyes. Our
      results demonstrate that TcMet functions in JH response and provide the critical
      evidence that the putative JH receptor Met mediates the antimetamorphic effect of
      JH.

PMID- 17537917
TI  - Late Pleistocene and Holocene environmental history of the Iguala Valley, Central
      Balsas Watershed of Mexico.
AB  - The origin of agriculture was a signal development in human affairs and as such
      has occupied the attention of scholars from the natural and social sciences for
      well over a century. Historical studies of climate and vegetation are closely
      associated with crop plant evolution because they can reveal the ecological
      contexts of plant domestication together with the antiquity and effects of
      agricultural practices on the environment. In this article, we present
      paleoecological evidence from three lakes and a swamp located in the Central
      Balsas watershed of tropical southwestern Mexico that date from 14,000 B.P. to
      the modern era. [Dates expressed in B.P. years are radiocarbon ages. Calibrated
      (calendar) ages, expressed as cal B.P., are provided for dates in the text.]
      Previous molecular studies suggest that maize (Zea mays L.) and other important
      crops such as squashes (Cucurbita spp.) were domesticated in the region. Our
      combined pollen, phytolith, charcoal, and sedimentary studies indicate that
      during the late glacial period (14,000-10,000 B.P.), lake beds were dry, the
      climate was cooler and drier, and open vegetational communities were more
      widespread than after the Pleistocene ended. Zea was a continuous part of the
      vegetation since at least the terminal Pleistocene. During the Holocene, lakes
      became important foci of human activity, and cultural interference with a species
      diverse tropical forest is indicated. Maize and squash were grown at lake edges
      starting between 10,000 and 5,000 B.P., most likely sometime during the first
      half of that period. Significant episodes of climatic drying evidenced between
      1,800 B.P. and 900 B.P. appear to be coeval with those documented in the Classic
      Maya region and elsewhere, showing widespread instability in the late Holocene
      climate.

PMID- 17537918
TI  - Nitric oxide inhibits Shiga-toxin synthesis by enterohemorrhagic Escherichia
      coli.
AB  - Shiga-toxin (Stx) is the cardinal virulence factor of enterohemorrhagic
      Escherichia coli (EHEC). The genes encoding Stx are carried by a lambdoid phage
      integrated in the bacterial genome and are fully expressed after a bacterial SOS
      response induced by DNA-damaging agents. Because nitric oxide (NO) is an
      essential mediator of the innate immune response of infected colonic mucosa, we
      aimed to determine its role in Stx production by EHEC. Here we demonstrate that
      chemical or cellular sources of NO inhibit spontaneous and mitomycin C-induced
      stx mRNA expression and Stx synthesis, without altering EHEC viability. The
      synthesis of stx phage is also reduced by NO. This inhibitory effect apparently
      occurs through the NO-mediated sensitization of EHEC because mutation of the NO
      sensor nitrite-sensitive repressor results in loss of NO inhibiting activity on
      stx expression. Thus our findings identify NO as an inhibitor of stx expressing
      phage propagation and Stx release and thus as a potential protective factor
      limiting the development of hemolytic syndromes.

PMID- 17537919
TI  - Proline-rich tyrosine kinase 2 regulates osteoprogenitor cells and bone
      formation, and offers an anabolic treatment approach for osteoporosis.
AB  - Bone is accrued and maintained primarily through the coupled actions of bone
      forming osteoblasts and bone-resorbing osteoclasts. Cumulative in vitro studies
      indicated that proline-rich tyrosine kinase 2 (PYK2) is a positive mediator of
      osteoclast function and activity. However, our investigation of PYK2-/- mice did
      not reveal evidence supporting an essential function for PYK2 in osteoclasts
      either in vivo or in culture. We find that PYK2-/- mice have high bone mass
      resulting from an unexpected increase in bone formation. Consistent with the in
      vivo findings, mouse bone marrow cultures show that PYK2 deficiency enhances
      differentiation and activity of osteoprogenitor cells, as does expressing a PYK2
      specific short hairpin RNA or dominantly interfering proteins in human
      mesenchymal stem cells. Furthermore, the daily administration of a small-molecule
      PYK2 inhibitor increases bone formation and protects against bone loss in
      ovariectomized rats, an established preclinical model of postmenopausal
      osteoporosis. In summary, we find that PYK2 regulates the differentiation of
      early osteoprogenitor cells across species and that inhibitors of the PYK2 have
      potential as a bone anabolic approach for the treatment of osteoporosis.

PMID- 17537920
TI  - The A-kinase anchoring protein (AKAP)-Lbc-signaling complex mediates alpha1
      adrenergic receptor-induced cardiomyocyte hypertrophy.
AB  - In response to various pathological stresses, the heart undergoes a pathological
      remodeling process that is associated with cardiomyocyte hypertrophy. Because
      cardiac hypertrophy can progress to heart failure, a major cause of lethality
      worldwide, the intracellular signaling pathways that control cardiomyocyte growth
      have been the subject of intensive investigation. It has been known for more than
      a decade that the small molecular weight GTPase RhoA is involved in the signaling
      pathways leading to cardiomyocyte hypertrophy. Although some of the hypertrophic
      pathways activated by RhoA have now been identified, the identity of the exchange
      factors that modulate its activity in cardiomyocytes is currently unknown. In
      this study, we show that AKAP-Lbc, an A-kinase anchoring protein (AKAP) with an
      intrinsic Rho-specific guanine nucleotide exchange factor activity, is critical
      for activating RhoA and transducing hypertrophic signals downstream of alpha1
      adrenergic receptors (ARs). In particular, our results indicate that suppression
      of AKAP-Lbc expression by infecting rat neonatal ventricular cardiomyocytes with
      lentiviruses encoding AKAP-Lbc-specific short hairpin RNAs strongly reduces both
      alpha1-AR-mediated RhoA activation and hypertrophic responses. Interestingly,
      alpha1-ARs promote AKAP-Lbc activation via a pathway that requires the alpha
      subunit of the heterotrimeric G protein G12. These findings identify AKAP-Lbc as
      the first Rho-guanine nucleotide exchange factor (GEF) involved in the signaling
      pathways leading to cardiomyocytes hypertrophy.

PMID- 17537921
TI  - Nuclear relocation of the nephrin and CD2AP-binding protein dendrin promotes
      apoptosis of podocytes.
AB  - Kidney podocytes and their slit diaphragms (SDs) form the final barrier to
      urinary protein loss. There is mounting evidence that SD proteins also
      participate in intracellular signaling pathways. The SD protein nephrin serves as
      a component of a signaling complex that directly links podocyte junctional
      integrity to actin cytoskeletal dynamics. Another SD protein, CD2-associated
      protein (CD2AP), is an adaptor molecule involved in podocyte homeostasis that can
      repress proapoptotic TGF-beta signaling in podocytes. Here we show that dendrin,
      a protein originally identified in telencephalic dendrites, is a constituent of
      the SD complex, where it directly binds to nephrin and CD2AP. In experimental
      glomerulonephritis, dendrin relocates from the SD to the nucleus of injured
      podocytes. High-dose, proapoptotic TGF-beta1 directly promotes the nuclear import
      of dendrin, and nuclear dendrin enhances both staurosporine- and TGF-beta1
      mediated apoptosis. In summary, our results identify dendrin as an SD protein
      with proapoptotic signaling properties that accumulates in the podocyte nucleus
      in response to glomerular injury and provides a molecular target to tackle
      proteinuric kidney diseases. Nuclear relocation of dendrin may provide a
      mechanism whereby changes in SD integrity could translate into alterations of
      podocyte survival under pathological conditions.

PMID- 17537922
TI  - Inducible XIST-dependent X-chromosome inactivation in human somatic cells is
      reversible.
AB  - During embryogenesis, the XIST RNA is expressed from and localizes to one X
      chromosome in females and induces chromosome-wide silencing. Although many
      changes to inactive X heterochromatin are known, the functional relationships
      between different modifications are not well understood, and studies of the
      initiation of X-inactivation have been largely confined to mouse. We now present
      a model system for human XIST RNA function in which induction of an XIST cDNA in
      somatic cells results in localized XIST RNA and transcriptional silencing.
      Chromatin immunoprecipitation and immunohistochemistry shows that this silencing
      need only be accompanied by a subset of heterochromatic marks and that these can
      differ between integration sites. Surprisingly, silencing is XIST-dependent,
      remaining reversible over extended periods. Deletion analysis demonstrates that
      the first exon of human XIST is sufficient for both transcript localization and
      the induction of silencing and that, unlike the situation in mice, the conserved
      repeat region is essential for both functions. In addition to providing
      mechanistic insights into chromosome regulation and formation of facultative
      heterochromatin, this work provides a tractable model system for the study of
      chromosome silencing and suggests key differences from mouse embryonic X
      inactivation.

PMID- 17537923
TI  - Linguistic tone is related to the population frequency of the adaptive
      haplogroups of two brain size genes, ASPM and Microcephalin.
AB  - The correlations between interpopulation genetic and linguistic diversities are
      mostly noncausal (spurious), being due to historical processes and geographical
      factors that shape them in similar ways. Studies of such correlations usually
      consider allele frequencies and linguistic groupings (dialects, languages,
      linguistic families or phyla), sometimes controlling for geographic, topographic,
      or ecological factors. Here, we consider the relation between allele frequencies
      and linguistic typological features. Specifically, we focus on the derived
      haplogroups of the brain growth and development-related genes ASPM and
      Microcephalin, which show signs of natural selection and a marked geographic
      structure, and on linguistic tone, the use of voice pitch to convey lexical or
      grammatical distinctions. We hypothesize that there is a relationship between the
      population frequency of these two alleles and the presence of linguistic tone and
      test this hypothesis relative to a large database (983 alleles and 26 linguistic
      features in 49 populations), showing that it is not due to the usual explanatory
      factors represented by geography and history. The relationship between genetic
      and linguistic diversity in this case may be causal: certain alleles can bias
      language acquisition or processing and thereby influence the trajectory of
      language change through iterated cultural transmission.

PMID- 17537924
TI  - Reading comprehension of deaf children with cochlear implants.
AB  - The reading comprehension and visual word recognition in 50 deaf children and
      adolescents with at least 3 years of cochlear implant (CI) use were evaluated.
      Their skills were contrasted with reference data of 500 deaf children without
      CIs. The reading comprehension level in children with CIs was expected to surpass
      that in deaf children without implants, partly via improved visual word
      recognition. Reading comprehension scores of children with implants were
      significantly better than those of deaf children without implants, although the
      performance in implant users was substantially lagging behind that in hearing
      children. Visual word recognition was better in children with CIs than in
      children without implants, in secondary education only. No difference in visual
      word recognition was found between the children with CIs and the hearing
      children, whereas the deaf children without implants showed a slightly poorer
      performance. The difference in reading comprehension performance of the deaf
      children with and without CIs remained present when visual word recognition was
      controlled for. This indicates that other reading-related skills were also
      contributing to the improved reading comprehension skills of deaf children with
      CIs.

PMID- 17537925
TI  - Employment tribunals and occupational health practitioners.

PMID- 17537927
TI  - Common mental health problems in the workplace: how can occupational physicians
      help?

PMID- 17537928
TI  - High-throughput, sensitive, and accurate multiplex PCR-microsphere flow cytometry
      system for large-scale comprehensive detection of respiratory viruses.
AB  - Human respiratory viruses are a diverse group of pathogens composed of hundreds
      of virus strains, and this presents a major challenge for diagnostic
      laboratories. To efficiently detect numerous viruses in a large epidemiologic
      study, we developed a fast, multitarget, sensitive, and specific assay named the
      Respiratory MultiCode-PLx Assay (RMA). The RMA utilizes improved multiplex PCR
      chemistry (EraGen MultiCode-PLx technology) coupled with high-throughput
      microsphere flow cytometry (Luminex). Eighteen sets of virus-specific multiplex
      PCR primers were developed based on the conserved sequences of all available
      respiratory-virus sequences for eight distinct groups: human rhinovirus (HRV),
      respiratory syncytial virus (RSV), parainfluenza virus (PIV), influenza virus
      (InfV), metapneumovirus, adenovirus (Ad), coronavirus, and enterovirus. Each
      primer set detected 20 cDNA copies of the intended target per sample and had no
      reaction with 60,000 copies of human genomic DNA. The accuracy and sensitivity of
      the RMA for detecting respiratory viruses in human samples were tested with two
      sets of clinical specimens. First, 101 nasal-wash specimens that were positive
      for HRV, RSV, InfV, PIV, or Ad by traditional techniques were reanalyzed by RMA,
      and all target viruses were detected with an overall sensitivity of 94% and
      specificity of 99%. Second, 103 nasal-wash samples from 5-year-old children with
      asthma and respiratory symptoms were analyzed; RMA detected viruses in 74
      specimens (71.8%) compared to only 24 (23.3%) by traditional culture and
      immunofluorescent-staining techniques. These results show that RMA is an
      accurate, sensitive, and practical test for respiratory-virus infections.

PMID- 17537929
TI  - Host genetic resistance to symptomatic norovirus (GGII.4) infections in Denmark.
AB  - A total of 61 individuals involved in five norovirus outbreaks in Denmark were
      genotyped at nucleotides 428 and 571 of the FUT2 gene, determining secretor
      status, i.e., the presence of ABH antigens in secretions and on mucosa. A strong
      correlation (P = 0.003) was found between the secretor phenotype and symptomatic
      disease, extending previous knowledge and confirming that nonsense mutations in
      the FUT2 gene provide protection against symptomatic norovirus (GGII.4)
      infections.

PMID- 17537930
TI  - Transmission of Enterocytozoon bieneusi between a child and guinea pigs.
AB  - An unusual Enterocytozoon bieneusi genotype was found in seven guinea pigs and a
      2-year-old child in the same household. The genetic uniqueness of the parasite,
      its wide occurrence in other guinea pigs in the community, and its absence in
      other children in the community suggest the possibility of zoonotic transmission
      of the infection to the study child.

PMID- 17537931
TI  - Development and evaluation of a test for tuberculosis in live European badgers
      (Meles meles) based on measurement of gamma interferon mRNA by real-time PCR.
AB  - A real-time PCR assay for the measurement of gamma interferon (IFN-gamma) mRNA in
      European badger (Meles meles) blood cultures was developed. The levels of IFN
      gamma mRNA in blood cultures stimulated with either bovine or avian tuberculin or
      specific mycobacterial antigens were compared with those in a nonstimulated
      control blood culture as the basis for determining the tuberculosis (TB) status
      of live badgers. The assay was validated by testing 247 animals for which there
      were matching data from postmortem examination and culture of tissues. Relative
      changes in the levels of IFN-gamma mRNA in response to bovine tuberculin and
      specific antigens were found to be greater among badgers with tissues positive
      for TB on culture. The test was at its most accurate (87% of test results were
      correct) by using blood cultures containing bovine tuberculin as the antigen and
      when the response to avian tuberculin was taken into account by subtracting the
      avian tuberculin response from the bovine tuberculin response. At a specificity
      of 90.7%, the test was 70.6% sensitive. At the same specificity, the current
      serological enzyme-linked immunosorbent assay for TB in badgers was only 53%
      sensitive. This work demonstrates that measurement of IFN-gamma mRNA by real-time
      PCR is a valid method for the detection of TB in live badgers and may provide an
      alternative to the current serological methods of diagnosis, the Brock test. The
      testing procedure can be completed within 5 h of receipt of the blood culture
      samples. In addition, the use of a molecular biology-based test offers the
      potential to fully automate the testing procedure through the use of robotics.

PMID- 17537932
TI  - Drug susceptibility testing of Mycobacterium tuberculosis complex by use of a
      high-throughput, reproducible, absolute concentration method.
AB  - Accurate drug susceptibility testing (DST) for Mycobacterium tuberculosis is
      highly important for both therapy guidance and surveillance of drug resistance.
      Although liquid medium DST methods are used increasingly and seem most efficient
      and fast, the high costs hamper widespread implementation. In addition, an
      inability to check the colony morphology of the growing bacteria is a
      disadvantage of these methods. Moreover, these methods discriminate only between
      susceptibility and resistance and do not determine the MIC. In this paper, we
      describe a low-cost, reproducible, high-throughput, proportional absolute
      concentration DST method. The method uses a concentration series of
      antituberculosis drugs, including pyrazinamide in 7H10 medium, distributed
      semiautomatically in 25-well plates. The performance of this 25-well DST method
      was evaluated by the World Health Organization and the International Union
      against Tuberculosis and Lung Disease in 10 rounds of proficiency testing
      regarding sensitivity, specificity, efficiency, reproducibility, and predictive
      value for resistance and susceptibility. The performance of the method for these
      characteristics was 100% for isoniazid and from 96 to 100% for rifampin, 91 to
      100% for streptomycin, and 85 to 100% for ethambutol. The method was 100%
      reproducible for all four drugs. The levels of drug resistance and the MIC
      distributions for the first-line antituberculosis drugs were determined for all
      7,956 M. tuberculosis strains isolated in The Netherlands from 1998 to 2005 and
      amounted to 7.5% for isoniazid, 1.4% for rifampin, 8.5% for streptomycin, and
      1.0% for ethambutol. Pyrazinamide testing was successful for 7,026 (88.3%) of the
      isolates and showed a resistance level of 0.8%.

PMID- 17537933
TI  - Sensitive detection of Mycoplasma pneumoniae in human respiratory tract samples
      by optimized real-time PCR approach.
AB  - To enhance the sensitivity of the available real-time PCR systems for the
      detection of Mycoplasma pneumoniae, we established a method to amplify copies of
      the repetitive element repMp1. In a study of respiratory tract samples, we found
      that, compared to the use of the conserved part of the P1 adhesin gene as a
      monocopy target, the use of the repMp1-PCR showed an increase in the detected
      genome equivalents by a factor of 22.

PMID- 17537934
TI  - Rapid detection directly from patient serum samples of human cytomegalovirus UL97
      mutations conferring ganciclovir resistance.
AB  - Ganciclovir-resistant cytomegalovirus can cause disease and death in transplant
      recipients. We describe here a rapid PCR- and sequencing-based assay for
      ganciclovir resistance that can be performed in 1 to 2 working days directly from
      patient specimens, without the need for amplification of the virus by cell
      culture. An evaluation of 120 sequential samples submitted for clinical testing
      revealed a variety of silent and amino acid mutations.

PMID- 17537935
TI  - Evidence for bovine origin of VP4 and VP7 genes of human group A rotavirus
      G6P[14] and G10P[14] strains.

PMID- 17537936
TI  - Evaluation and improvement of real-time PCR assays targeting lytA, ply, and psaA
      genes for detection of pneumococcal DNA.
AB  - The accurate diagnosis of pneumococcal disease has frequently been hampered not
      only by the difficulties in obtaining isolates of the organism from patient
      specimens but also by the misidentification of pneumococcus-like viridans group
      streptococci (P-LVS) as Streptococcus pneumoniae. This is especially critical
      when the specimen comes from the respiratory tract. In this study, three novel
      real-time PCR assays designed for the detection of specific sequence regions of
      the lytA, ply, and psaA genes were developed (lytA-CDC, ply-CDC, and psaA,
      respectively). These assays showed high sensitivity (<10 copies for lytA-CDC and
      ply-CDC and an approximately twofold less sensitivity for psaA). Two additional
      real-time PCR assays for lytA and ply described previously for pneumococcal DNA
      detection were also evaluated. A panel of isolates consisting of 67 S. pneumoniae
      isolates (44 different serotypes and 3 nonencapsulated S. pneumoniae isolates
      from conjunctivitis outbreaks) and 104 nonpneumococcal isolates was used. The 67
      S. pneumoniae isolates were reactive in all five assays. The new real-time
      detection assays targeting the lytA and psaA genes were the most specific for the
      detection of isolates confirmed to be S. pneumoniae, with lytA-CDC showing the
      greatest specificity. Both ply PCRs were positive for all isolates of S.
      pseudopneumoniae, along with 13 other isolates of other P-LVS isolates confirmed
      to be non-S. pneumoniae by DNA-DNA reassociation. Thus, the use of the ply gene
      for the detection of pneumococci can lead to false-positive reactions in the
      presence of P-LVS. The five assays were applied to 15 culture-positive
      cerebrospinal fluid specimens with 100% sensitivity; and serum and ear fluid
      specimens were also evaluated. Both the lytA-CDC and psaA assays, particularly
      the lytA-CDC assay, have improved specificities compared with those of currently
      available assays and should therefore be considered the assays of choice for the
      detection of pneumococcal DNA, particularly when upper respiratory P-LVS might be
      present in the clinical specimen.

PMID- 17537937
TI  - Evaluation of the GenoType MTBDRplus assay for rifampin and isoniazid
      susceptibility testing of Mycobacterium tuberculosis strains and clinical
      specimens.
AB  - The new GenoType MTBDRplus assay (Hain Lifescience GmbH, Nehren, Germany) was
      tested with 125 clinical isolates and directly with 72 smear-positive sputum
      specimens for its ability to detect rifampin (RMP) and isoniazid (INH) resistance
      in Mycobacterium tuberculosis complex (MTBC) strains. In total, 106
      RMP(r)/INH(r), 10 RMP(s)/INH(r), and 80 RMP(s)/INH(s) MTBC strains were
      comparatively analyzed with the new and the old MTBDR assays. Besides the
      detection of mutations within the 81-bp hot spot region of rpoB and katG codon
      315, the GenoType MTBDRplus assay is designed to detect mutations in the
      regulatory region of inhA. The applicability of the new assay directly to
      specimens was shown, since 71 of 72 results for smear-positive sputa and all 125
      results for clinical isolates were interpretable and no discrepancies compared
      with the results of real-time PCR or DNA sequencing were obtained. In comparison
      to conventional drug susceptibility testing, both assays were able to identify
      RMP resistance correctly in 74 of 75 strains (98.7%) and 30 of 31 specimens
      (96.8%). The misidentification of RMP resistance was obtained for two strains
      containing rpoB P533L mutations. Compared to the old MTBDR assay, the new
      GenoType MTBDRplus assay enhanced the rate of detection of INH resistance from 66
      (88.0%) to 69 (92.0%) among the 75 INH-resistant strains and 36 (87.8%) to 37
      (90.2%) among the 41 specimens containing INH-resistant strains. Thus, the new
      GenoType MTBDRplus assay represents a reliable and upgraded tool for the
      detection of INH and RMP resistance in strains or directly from smear-positive
      specimens.

PMID- 17537938
TI  - Nonsporulating clinical isolate identified as Petromyces alliaceus (anamorph
      Aspergillus alliaceus) by morphological and sequence-based methods.
AB  - Concerted morphological and sequencing-based strategies revealed the identity of
      a nonsporulating clinical isolate as Petromyces alliaceus (anamorph Aspergillus
      alliaceus). This rare Aspergillus sp. was recovered as the etiological agent of
      invasive pulmonary aspergillosis and had reduced in vitro susceptibilities to
      amphotericin B and caspofungin, which correlated with clinical failure of
      therapy.

PMID- 17537939
TI  - New highly divergent rRNA sequence among biodiverse genotypes of Enterocytozoon
      bieneusi strains isolated from humans in Gabon and Cameroon.
AB  - Intestinal microsporidiosis due to Enterocytozoon bieneusi is a leading cause of
      chronic diarrhea in severely immunocompromised human immunodeficiency virus (HIV)
      positive patients. It may be a public health problem in Africa due to the
      magnitude of the HIV pandemic and to poor sanitary conditions. We designed two
      prevalence studies of E. bieneusi in Central Africa, the first with HIV-positive
      patients from an urban setting in Gabon and the second with a nonselected rural
      population in Cameroon. Stool samples were analyzed by an immunofluorescence
      antibody test and PCR. Twenty-five out of 822 HIV-positive patients from Gabon
      and 22 out of 758 villagers from Cameroon were found to be positive for E.
      bieneusi. The prevalence rates of the two studies were surprisingly similar (3.0%
      and 2.9%). Genotypic analysis of the internal transcribed spacer region of the
      rRNA gene showed a high degree of diversity in samples from both countries. In
      Gabon, 15 isolates showed seven different genotypes: the previously reported
      genotypes A, D, and K along with four new genotypes, referred to as CAF1, CAF2,
      CAF3, and CAF4. In Cameroon, five genotypes were found in 20 isolates: the known
      genotypes A, B, D, and K and the new genotype CAF4. Genotypes A and CAF4
      predominated in Cameroon, whereas K, CAF4, and CAF1 were more frequent in Gabon,
      suggesting that different genotypes present differing risks of infection
      associated with immune status and living conditions. Phylogenetic analysis of the
      new genotype CAF4, identified in both HIV-negative and HIV-positive subjects,
      indicates that it represents a highly divergent strain.

PMID- 17537940
TI  - Typing of human enterovirus by partial sequencing of VP2.
AB  - The sequencing of the VP1 hypervariable region of the human enterovirus (HEV)
      genome has become the reference test for typing field isolates. This study
      describes a new strategy for typing HEV at the serotype level that uses a reverse
      transcription-PCR assay targeting the central part of the VP2 capsid protein. Two
      pairs of primers were used to amplify a fragment of 584 bp (with reference to the
      PV-1 sequence) or a part of it (368 bp) for typing. For a few strains not
      amplified by the first PCR, seminested primers enhanced the sensitivity (which
      was found to be approximately 10(-1) and 10(-4) 50% tissue culture infective dose
      per reaction tube for the first and seminested assay, respectively). The typing
      method was then applied to 116 clinical and environmental strains of HEV. Sixty
      one typeable isolates were correctly identified at the serotype level by
      comparison to seroneutralization. Forty-eight of 55 "untypeable" strains (87.3%)
      exhibited the same serotype using VP1 and VP2 sequencing methods. For six strains
      (four identified as EV-71, one as E-9, and one as E-30 by the VP2 method), no
      amplification was obtained by the VP1 method. The last strain, typed as CV-B4 by
      VP1 and CV-B3 by VP2 and monovalent antiserum, could exhibit recombination within
      the capsid region. Although the VP2 method was tested on only 36 of the 68 HEV
      serotypes, it appears to be a promising strategy for typing HEV strains isolated
      on a routine basis. The good sensitivity of the seminested technique could avoid
      cell culture and allow HEV typing directly from PCR products.

PMID- 17537941
TI  - Factors affecting serum concentrations of hepatitis C virus (HCV) RNA in HCV
      genotype 1-infected patients with chronic hepatitis.
AB  - The serum concentration of hepatitis C virus (HCV) RNA is usually stable (4 to 8
      log(10) IU/ml) in untreated patients with chronic hepatitis C. While this
      baseline HCV RNA concentration ([HCV RNA](BL)) is predictive of a sustained
      virologic response to treatment, its determinants are only partially identified.
      We therefore analyzed the baseline characteristics of 2,472 HCV genotype 1
      infected patients to identify correlations with gender, age, race, weight, body
      mass index (BMI), HCV acquisition mode, HCV subtype, alanine aminotransferase
      concentration, or histopathologic changes in the liver. After separation of the
      data according to four [HCV RNA](BL) groups (< or =5.0, >5.0 to 5.6, >5.6 to 5.9,
      and >5.9 log(10) IU/ml), we determined that increasing [HCV RNA](BL) correlated
      (P < 0.05) with increasing proportions of patients who were male, >40 years of
      age, or heavier (a weight of >85 kg or a BMI of >27 kg/m(2)). Histologic activity
      index (HAI) data were available for 1,304 of these patients: increasing [HCV
      RNA](BL) correlated with higher fibrosis and necrosis-inflammation scores. As a
      continuous variable, [HCV RNA](BL) correlated with age, gender, weight
      (continuous or < or =85 versus >85 kg), BMI (continuous or < or =27 versus >27
      kg/m(2)), subtype, fibrosis score, and necrosis-inflammation score; however,
      multiple-regression analysis yielded P values of <0.1 only for age, gender, BMI
      (< or =27 versus >27 kg/m(2)), and fibrosis score. While our findings are
      suggestive of a role for these factors in maintenance of the pretreatment state
      of HCV infection, the multiple-regression model accounted for only < or =4.6% of
      the [HCV RNA](BL) differences between individuals (R(2) = 0.046 for 1,304
      patients with HAI scores; 0.043 for all 2,472 patients).

PMID- 17537942
TI  - New variable-number tandem-repeat markers for typing Mycobacterium avium subsp.
      paratuberculosis and M. avium strains: comparison with IS900 and IS1245
      restriction fragment length polymorphism typing.
AB  - Mycobacterium avium subsp. paratuberculosis, the etiological agent of
      paratuberculosis, affects a wide range of domestic ruminants and has been
      suggested to be involved in Crohn's disease in humans. Most available methods for
      identifying and differentiating strains of this difficult species are technically
      demanding and have limited discriminatory power. Here, we report the
      identification of novel PCR-based typing markers consisting of variable-number
      tandem repeats (VNTRs) of genetic elements called mycobacterial interspersed
      repetitive units (MIRUs). Eight markers were applied to 183 M. avium subsp.
      paratuberculosis isolates from bovine, caprine, ovine, cervine, leporine, and
      human origins from 10 different countries and to 82 human isolates of the closely
      related species M. avium from France. Among the M. avium subsp. paratuberculosis
      isolates, 21 patterns were found by MIRU-VNTR typing, with a discriminatory index
      of 0.751. The predominant R01 IS900 restriction fragment length polymorphism
      type, comprising 131 isolates, was divided into 15 MIRU-VNTR types. Among the 82
      M. avium isolates, the eight MIRU-VNTR loci distinguished 30 types, none of which
      was shared by M. avium subsp. paratuberculosis isolates, resulting in a
      discriminatory index of 0.889. Our results suggest that MIRU-VNTR typing is a
      fast typing method that, in combination with other methods, might prove to be
      optimal for PCR-based molecular epidemiological studies of M. avium/M. avium
      subsp. paratuberculosis pathogens. In addition, presumably identical M. avium
      subsp. paratuberculosis 316F vaccine strains originating from the Weybridge
      laboratory and from different commercial batches from Merial actually differed by
      one or both typing methods. These results indicate a substantial degree of
      genetic drift among different vaccine preparations, which has important
      implications for prophylactic approaches.

PMID- 17537943
TI  - Abilities of APTIMA, AMPLICOR, and ProbeTec assays to detect Chlamydia
      trachomatis and Neisseria gonorrhoeae in PreservCyt ThinPrep Liquid-based Pap
      samples.
AB  - Infections with Chlamydia trachomatis and Neisseria gonorrhoeae are often
      asymptomatic. Liquid-based Pap (L-Pap) screening may provide samples for testing
      by commercial assays. Women attending a health clinic or a street youth clinic
      had a PreservCyt ThinPrep sample and a cervical swab (CS) collected. The L-Pap
      sample was tested for cytopathology; then 1 ml was transferred to an L-Pap
      specimen transfer tube for testing by the Gen-Probe APTIMA assays (APTIMA Combo 2
      [AC2], APTIMA C. trachomatis [ACT], and APTIMA N. gonorrhoeae [AGC]). The
      residual L-Pap sample was tested for C. trachomatis and N. gonorrhoeae using
      Roche AMPLICOR (AMP) and Becton Dickinson ProbeTec (PT). The CS was tested by
      AC2. A patient was considered infected if two specimens were positive or if a
      single specimen was positive in two tests. The prevalence of infection was 10%
      (29/290) for C. trachomatis and 2.4% (7/290) for N. gonorrhoeae. Most of the
      positive patients had specimens that were reactive in all assays (20/29 for C.
      trachomatis; 6/7 for N. gonorrhoeae). Four patients had double infections. The
      sensitivities and specificities of the various tests for the specimens tested
      were as follows. For C. trachomatis on L-Pap, sensitivity and specificity were
      100 and 98.1%, respectively, for ACT, 93.1 and 98.8% for AC2, 86.2 and 91.2% for
      AMP, and 72.4 and 92.7% for PT. For N. gonorrhoeae on L-Pap, sensitivity and
      specificity were 100% for both AGC and AC2, 85.7 and 100% for AMP, and 85.7 and
      100% for PT. For AC2 with CSs, sensitivity and specificity were 93.1 and 98.5%,
      respectively, for C. trachomatis, and both were 100% for N. gonorrhoeae. There
      were significant differences in sensitivity and specificity (P < 0.001). The
      APTIMA assays were more sensitive and specific than AMP or PT for detecting
      women's C. trachomatis and/or N. gonorrhoeae infections by testing ThinPrep
      samples.

PMID- 17537944
TI  - Puumala hantavirus viremia diagnosed by real-time reverse transcriptase PCR using
      samples from patients with hemorrhagic fever and renal syndrome.
AB  - Puumala virus (PUUV) is the endemic hantavirus in northern Sweden and causes
      nephropathia epidemica (NE), a milder form of hemorrhagic fever with renal
      syndrome. There is a need for fast and reliable diagnostics to differentiate the
      disease from other infections. By aligning virus RNA sequences isolated from 11
      different bank voles and one human patient, we designed a real-time reverse
      transcriptase (RT) PCR method for detection of PUUV RNA. The real-time RT-PCR
      assay showed linearity from 20 to 2 x 10(6) virus copies with a correlation
      coefficient above 0.98 to 0.99 for all experiments. The detection threshold for
      PUUV cDNA was two copies per reaction. A two-step qualitative RT-PCR to detect
      PUUV RNA showed 100% concordance with the real-time RT-PCR assay. PUUV RNA
      viremia was detected in 33 of 34 PUUV immunoglobulin M (IgM)-positive patients
      with typical clinical NE disease from the region of endemicity. One PUUV IgM
      negative sample had PUUV RNA, and 4 days later, the patient was IgM positive. Of
      samples with indeterminate IgM, 43% were PUUV RNA positive. The kinetics of
      antibody titers and PUUV viremia were studied, and five of six NE patients
      displayed a decrease in PUUV viremia a few days after disease outbreak coupled
      with an increase in PUUV IgM and IgG. In one patient with continuously high PUUV
      RNA levels but low IgM and no IgG response, the infection was lethal. These
      findings demonstrated that real-time RT-PCR is a useful method for diagnosis of
      PUUV viremia and for detecting PUUV RNA at early time points, before the
      appearance of IgM antibodies.

PMID- 17537945
TI  - Delayed processing of blood samples influences time to positivity of blood
      cultures and results of Gram stain-acridine orange leukocyte Cytospin test.
AB  - We investigated in vitro whether storage of blood samples influences the time to
      positivity used for the calculation of the differential time to positivity (DTP)
      and the results of the Gram stain-acridine orange leukocyte Cytospin (AOLC) test.
      A 24-hour storage of blood samples at room temperature may lead to false-negative
      DTP and false-positive Gram stain-AOLC test results, whereas storage at 4 degrees
      C does not.

PMID- 17537947
TI  - In-house growth-promoting transport system for Neisseria gonorrhoeae.
AB  - Eno powder (GlaxoSmithKline), an antacid preparation readily available over the
      counter, was used instead of a CO(2) generator for the growth of 15 strains of
      Neisseria gonorrhoeae obtained from men with urethritis. Due to its easy
      accessibility and low cost, Eno powder can be useful in developing countries for
      transporting clinical specimens from resource-poor peripheral labs to reference
      laboratories.

PMID- 17537946
TI  - Clonal distribution of superantigen genes in clinical Staphylococcus aureus
      isolates.
AB  - Staphylococcus aureus is both a successful human commensal and a major pathogen.
      The elucidation of the molecular determinants of virulence, in particular
      assessment of the contributions of the genetic background versus those of mobile
      genetic elements (MGEs), has proved difficult in this variable species. To
      address this, we simultaneously determined the genetic backgrounds (spa typing)
      and the distributions of all 19 known superantigens and the exfoliative toxins A
      and D (multiplex PCR) as markers for MGEs. Methicillin- sensitive S. aureus
      strains from Pomerania, 107 nasal and 88 blood culture isolates, were
      investigated. All superantigen-encoding MGEs were linked more or less tightly to
      the genetic background. Thus, each S. aureus clonal complex was characterized by
      a typical repertoire of superantigen and exfoliative toxin genes. However, within
      each S. aureus clonal complex and even within the same spa type, virulence gene
      profiles varied remarkably. Therefore, virulence genes of nasal and blood culture
      isolates were separately compared in each clonal complex. The results indicated a
      role in infection for the MGE harboring the exfoliative toxin D gene. In
      contrast, there was no association of superantigen genes with bloodstream
      invasion. In summary, we show here that the simultaneous assessment of virulence
      gene profiles and the genetic background increases the discriminatory power of
      genetic investigations into the mechanisms of S. aureus pathogenesis.

PMID- 17537948
TI  - Vaginal Staphylococcus aureus superantigen profile shift from 1980 and 1981 to
      2003, 2004, and 2005.
AB  - We determined vaginal Staphylococcus aureus superantigens. Staphylococci were
      quantified from tampons/diaphragms in 2003 to 2005, with counts compared to those
      determined in 1980 and 1981. In 2003 to 2005, more women were colonized than in
      1980 and 1981 (23 versus 12%). Enterotoxins G and I and enterotoxin-like
      superantigens M and N declined, but enterotoxin-like superantigens K, L, and Q
      increased.

PMID- 17537949
TI  - Methicillin-resistant Staphylococcus aureus (MRSA) detection: comparison of two
      molecular methods (IDI-MRSA PCR assay and GenoType MRSA Direct PCR assay) with
      three selective MRSA agars (MRSA ID, MRSASelect, and CHROMagar MRSA) for use with
      infection-control swabs.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) is an increasing problem.
      Rapid detection of MRSA-colonized patients has the potential to limit spread of
      the organism. We evaluated the sensitivities and specificities of MRSA detection
      by two molecular methods (IDI-MRSA PCR assay and GenoType MRSA Direct PCR assay)
      and three selective MRSA agars (MRSA ID, MRSASelect, and CHROMagar MRSA), using
      205 (101 nasal, 52 groin, and 52 axillary samples) samples from consecutive known
      MRSA-infected and/or -colonized patients. All detection methods had higher MRSA
      detection rates for nasal swabs than for axillary and groin swabs. Detection of
      MRSA by IDI-MRSA was the most sensitive method, independent of the site (94% for
      nasal samples, 80% for nonnasal samples, and 90% overall). The sensitivities of
      the GenoType MRSA Direct assay and the MRSA ID, MRSASelect, and CHROMagar MRSA
      agars with nasal swabs were 70%, 72%, 68%, and 75%, respectively. All detection
      methods had high specificities (95 to 99%), independent of the swab site.
      Extended incubation for a further 24 h with selective MRSA agars increased the
      detection of MRSA, with a corresponding decline in specificity secondary to a
      significant increase in false-positive results. There was a noticeable difference
      in test performance of the GenoType MRSA Direct assay in detection of MRSA (28/38
      samples [74%]) compared with detection of nonmultiresistant MRSA (17/31 samples
      [55%]) (susceptible to two or more non-beta-lactam antibiotics). This was not
      observed with selective MRSA agar plates or IDI-MRSA. Although it is more
      expensive, in addition to rapid turnaround times of 2 to 4 h, IDI-MRSA offers
      greater detection of MRSA colonization, independent of the swab site, than do
      conventional selective agars and GenoType MRSA Direct.

PMID- 17537950
TI  - Mycobacterium simiae complex infection in an immunocompetent child.
AB  - Nontuberculous mycobacteria are ubiquitous in the environment but rarely infect
      immunocompetent patients. We describe a pediatric case of Mycobacterium simiae
      complex lymphadenitis in an immunocompetent child and review the natural history,
      clinical manifestations, diagnosis, and current management of the disease.

PMID- 17537951
TI  - Simplified and reliable scheme for species-level identification of Staphylococcus
      clinical isolates.
AB  - Reliable and rapid identification of staphylococcal strains continues to be a
      problem faced by many microbiology laboratories. This study evaluates a
      simplified method that uses a flowchart to assist in the identification of 12
      clinical species of Staphylococcus, including eight subspecies. A total of 198
      isolates and 11 control strains were identified by the reference method, which
      employed 22 tests. The results were compared with those obtained by two other
      methods: an automated system (MicroScan WalkAway) and a simplified method
      composed of nine tests. The simplified scheme showed an accuracy of 98.5%, while
      the automated method showed an accuracy of 79.3% (P < 0.001), in identifying
      staphylococcal species. Atypical phenotypic profiles were detected by both the
      reference (55.6%) and the simplified (19.7%) methods. The simplified method
      proposed here was shown to be reliable, with the advantage of being more
      practical and economic than the reference method.

PMID- 17537952
TI  - Antigen-retrieval procedure for bromodeoxyuridine immunolabeling with concurrent
      labeling of nuclear DNA and antigens damaged by HCl pretreatment.

PMID- 17537953
TI  - A critical time for new neurons in the adult hippocampus.

PMID- 17537954
TI  - The role of the mirror system in mapping complex sounds into actions.

PMID- 17537955
TI  - The functional impact of the intrastriatal dopamine neuron grafts in parkinsonian
      rats is reduced with advancing disease.
AB  - Clinical trials involving intrastriatal transplants of human embryonic
      mesencephalic tissue have provided proof-of-principle that nigral dopamine (DA)
      neurons can survive and functionally integrate into the host neural circuitry.
      However, the degree of graft-induced symptomatic relief differs significantly
      between the patients. This variability has led to investigations aimed at
      identifying factors that could affect the clinical outcome. The extent and
      pattern of dopaminergic denervation in the brain may be one of the major
      determinants of the functional outcome after intrastriatal DA cell grafts. Here,
      we report that in animals subjected to an intrastriatal 6-hydroxydopamine lesion
      of the striatal dopaminergic afferent, the integrity of the host dopaminergic
      innervation outside the areas innervated by the graft is critical for optimal
      function of DA neurons placed in the striatum. Established graft-induced
      functional recovery, as assessed in the stepping and cylinder tests, was
      compromised in animals in which the dopaminergic lesion was extended to include
      also the medial and ventral striatum as well as the cortical and limbic DA
      projections. Poor clinical outcome after transplantation may, thus, at least in
      part, be caused by dopaminergic denervation in areas outside the graft-innervated
      territories, and similarly beneficial effects initially observed in patients may
      regress if the degeneration of the host extrastriatal DA projection systems
      proceeds with advancing disease. This would have two implications: first,
      patients with advanced disease involving the ventral striatum and/or nonstriatal
      DA projections would be unlikely to respond well to intrastriatal DA grafts and,
      second, to retain the full benefit of the grafts, progression of the disease
      should be avoided by, for example, combining cell therapy with a neuroprotective
      approach.

PMID- 17537956
TI  - Presynaptic G-protein-coupled receptors regulate synaptic cleft glutamate via
      transient vesicle fusion.
AB  - When synaptic vesicles fuse with the plasma membrane, they may completely
      collapse or fuse transiently. Transiently fusing vesicles remain structurally
      intact and therefore have been proposed to represent a form of rapid vesicle
      recycling. However, the impact of a transient synaptic vesicle fusion event on
      neurotransmitter release, and therefore on synaptic transmission, has yet to be
      determined. Recently, the molecular mechanism by which a serotonergic presynaptic
      G-protein-coupled receptor (GPCR) regulates synaptic vesicle fusion and inhibits
      synaptic transmission was identified. By making paired electrophysiological
      recordings in the presence and absence of low-affinity antagonists, we now
      demonstrate that activation of this presynaptic GPCR lowers the peak synaptic
      cleft glutamate concentration independently of the probability of vesicle fusion.
      Furthermore, this change in cleft glutamate concentration differentially inhibits
      synaptic NMDA and AMPA receptor-mediated currents. We conclude that a presynaptic
      GPCR regulates the profile of glutamate in the synaptic cleft through altering
      the mechanism of vesicle fusion leading to qualitative as well as quantitative
      changes in neural signaling.

PMID- 17537957
TI  - Plant-derived flavanol (-)epicatechin enhances angiogenesis and retention of
      spatial memory in mice.
AB  - Diet and exercise have a profound impact on brain function. In particular,
      natural nutrients found in plants may influence neuronal survival and plasticity.
      Here, we tested whether consumption of a plant-derived flavanol, (-)epicatechin,
      enhances cognition in sedentary or wheel-running female C57BL/6 mice. Retention
      of spatial memory in the water maze was enhanced by ingestion of (-)epicatechin,
      especially in combination with exercise. Improved spatial memory was associated
      with increased angiogenesis and neuronal spine density, but not newborn cell
      survival, in the dentate gyrus of the hippocampus. Moreover, microarray analysis
      showed upregulation of genes associated with learning and downregulation of
      markers of neurodegeneration in the hippocampus. Together, our data show that
      ingestion of a single flavanol improves spatial memory retention in adult
      mammals.

PMID- 17537958
TI  - Multisensory integration shortens physiological response latencies.
AB  - Individual superior colliculus (SC) neurons integrate information from multiple
      sensory sources to enhance their physiological response. The response of an SC
      neuron to a cross-modal stimulus combination can not only exceed the best
      component unisensory response but can also exceed their arithmetic sum (i.e.,
      superadditivity). The present experiments were designed to investigate the
      temporal profile of multisensory integration in this model system. We found that
      cross-modal stimuli frequently shortened physiological response latencies (mean
      shift, 6.2 ms) and that response enhancement was greatest in the initial phase of
      the response (the phenomenon of initial response enhancement). The vast majority
      of the responses studied evidenced superadditive computations, most often at the
      beginning of the multisensory response.

PMID- 17537959
TI  - Mitogen-activated protein kinase upregulates the dendritic translation machinery
      in long-term potentiation by controlling the mammalian target of rapamycin
      pathway.
AB  - Protein synthesis is required for persistent forms of synaptic plasticity,
      including long-term potentiation (LTP). A key regulator of LTP-related protein
      synthesis is mammalian target of rapamycin (mTOR), which is thought to modulate
      translational capacity by facilitating the synthesis of particular components of
      the protein synthesis machinery. Recently, extracellularly regulated kinase (ERK)
      also was shown to mediate plasticity-related translation, an effect that may
      involve regulation of the mTOR pathway. We studied the interaction between the
      mTOR and ERK pathways in hippocampal LTP induced at CA3-CA1 synapses by high
      frequency synaptic stimulation (HFS). Within minutes after HFS, the expression of
      multiple translational proteins, the synthesis of which is under the control of
      mTOR, increased in area CA1 stratum radiatum. This upregulation was detected in
      pyramidal cell dendrites and was blocked by inhibitors of the ERK pathway. In
      addition, ERK mediated the stimulation of mTOR by HFS. The possibility that ERK
      regulates mTOR by acting at a component further upstream in the
      phosphatidylinositide 3-kinase (PI3K)-mTOR pathway was tested by probing the
      phosphorylation of p90-S6 kinase, phosphoinositide-dependent kinase 1 (PDK1), and
      Akt. ERK inhibitors blocked HFS-induced phosphorylation of all three proteins at
      sites implicated in the regulation of mTOR. Moreover, a component of basal and
      HFS-induced ERK activity depended on PI3K, indicating that mTOR-mediated protein
      synthesis in LTP requires coincident and mutually dependent activity in the PI3K
      and ERK pathways. The role of ERK in regulating PDK1 and Akt, with their
      extensive effects on cellular function, has important implications for the
      coordinated response of the neuron to LTP-inducing stimulation.

PMID- 17537960
TI  - Haloperidol treatment after high-dose methamphetamine administration is
      excitotoxic to GABA cells in the substantia nigra pars reticulata.
AB  - The therapeutic management of methamphetamine (METH)-induced psychoses often
      involves treatment with the typical antipsychotic drug and dopamine D2 receptor
      antagonist haloperidol. We report here that subchronic haloperidol administration
      after a high-dose regimen of METH produces a heretofore unrecognized toxicity to
      GABAergic cells, as reflected by GAD67 mRNA expression histochemistry, in the rat
      substantia nigra pars reticulata (SNr) through an acute and persistent
      augmentation of glutamate release, NMDA receptor activation, and DNA
      fragmentation. The dopaminergic cells in the substantia nigra pars compacta were
      unaffected by METH or haloperidol alone or the combination of METH and
      haloperidol. These findings suggest that the current therapeutic management of
      METH-induced psychoses with haloperidol may be contraindicated because of a
      resultant GABAergic cell death in the SNr, which may predispose some individuals
      to the development of hyperkinetic movement disorders and seizures.

PMID- 17537961
TI  - Nav1.1 localizes to axons of parvalbumin-positive inhibitory interneurons: a
      circuit basis for epileptic seizures in mice carrying an Scn1a gene mutation.
AB  - Loss-of-function mutations in human SCN1A gene encoding Nav1.1 are associated
      with a severe epileptic disorder known as severe myoclonic epilepsy in infancy.
      Here, we generated and characterized a knock-in mouse line with a loss-of
      function nonsense mutation in the Scn1a gene. Both homozygous and heterozygous
      knock-in mice developed epileptic seizures within the first postnatal month.
      Immunohistochemical analyses revealed that, in the developing neocortex, Nav1.1
      was clustered predominantly at the axon initial segments of parvalbumin-positive
      (PV) interneurons. In heterozygous knock-in mice, trains of evoked action
      potentials in these fast-spiking, inhibitory cells exhibited pronounced spike
      amplitude decrement late in the burst. Our data indicate that Nav1.1 plays
      critical roles in the spike output from PV interneurons and, furthermore, that
      the specifically altered function of these inhibitory circuits may contribute to
      epileptic seizures in the mice.

PMID- 17537962
TI  - Development and plasticity of spontaneous activity and Up states in cortical
      organotypic slices.
AB  - Cortical computations are an emergent property of neural dynamics. To understand
      how neural dynamics emerges within local cortical networks, we characterized the
      development and underlying mechanisms of spontaneous dynamics in cortical
      organotypic slices. We observed not only a quantitative increase in the levels of
      spontaneous dynamics, but a qualitative transition from brief bursts of activity
      to well defined Up states during the first 4 weeks in vitro. Analysis of cellular
      and synaptic properties indicates that these changes are driven by increasing
      excitatory drive accompanied by changes in the balance of excitation and
      inhibition. Examination of the structure of spontaneous dynamics revealed no
      evidence of precisely repeating patterns. Slices exposed to chronic patterned
      stimulation exhibited decreased levels of spontaneous activity, suggesting
      homeostatic control of the levels of network activity. Together, these results
      suggest that Up states reflect a fundamental mode of network dynamics that
      emerges through the orchestrated regulation of multiple cellular and synaptic
      properties in parallel.

PMID- 17537963
TI  - Cell cycle regulator E2F4 is essential for the development of the ventral
      telencephalon.
AB  - Early forebrain development is characterized by extensive proliferation of neural
      precursors coupled with complex structural transformations; however, little is
      known regarding the mechanisms by which these processes are integrated. Here, we
      show that deficiency of the cell cycle regulatory protein, E2F4, results in the
      loss of ventral telencephalic structures and impaired self-renewal of neural
      precursor cells. The mechanism underlying aberrant ventral patterning lies in a
      dramatic loss of Sonic hedgehog (Shh) expression specifically in this region. The
      E2F4-deficient phenotype can be recapitulated by interbreeding mice heterozygous
      for E2F4 with those lacking one allele of Shh, suggesting a genetic interaction
      between these pathways. Treatment of E2F4-deficient cells with a Hh agonist
      rescues stem cell self-renewal and cells expressing the homeodomain proteins that
      specify the ventral telencephalic structures. Finally, we show that E2F4
      deficiency results in impaired activity of Shh forebrain-specific enhancers. In
      conclusion, these studies establish a novel requirement for the cell cycle
      regulatory protein, E2F4, in the development of the ventral telencephalon.

PMID- 17537964
TI  - Hedgehog signaling in the subventricular zone is required for both the
      maintenance of stem cells and the migration of newborn neurons.
AB  - We examined the postnatal consequences of removing Hedgehog signaling within the
      adult stem cell niche. Although at birth the subventricular zone appears normal
      in mice lacking Hedgehog signaling, by postnatal day 8 it is greatly impaired,
      and cell death is increased. In addition, both the quiescent B stem cell
      population and transit-amplifying C cells become depleted postnatally. In
      contrast, the A cell population expands precociously, mostly fails to migrate to
      the olfactory bulbs, and is ultimately also depleted by postnatal day 30. In
      vitro and in vivo analyses demonstrate that this failure in migration is a result
      of nonautonomous signaling, possibly caused by a reduction in Slit1 ligand in A
      cells. These results suggest that Hedgehog signaling is required for the
      maintenance of the B and C cell populations and indirectly for the migration of
      the neurons that are generated from the adult stem cell niche.

PMID- 17537965
TI  - Regulation of the intermediate filament protein nestin at rodent neuromuscular
      junctions by innervation and activity.
AB  - The intermediate filament nestin is localized postsynaptically at rodent
      neuromuscular junctions. The protein forms a filamentous network beneath and
      between the synaptic gutters, surrounds myofiber nuclei, and is associated with Z
      discs adjacent to the junction. In situ hybridization shows that nestin mRNA is
      synthesized selectively by synaptic myonuclei. Although weak immunoreactivity is
      present in myelinating Schwann cells that wrap the preterminal axon, nestin is
      not detected in the terminal Schwann cells (tSCs) that cover the nerve terminal
      branches. However, after denervation of muscle, nestin is upregulated in tSCs and
      in SCs within the nerve distal to the lesion site. In contrast, immunoreactivity
      is strongly downregulated in the muscle fiber. Transgenic mice in which the
      nestin neural enhancer drives expression of a green fluorescent protein (GFP)
      reporter show that the regulation in SCs is transcriptional. However, the
      postsynaptic expression occurs through enhancer elements distinct from those
      responsible for regulation in SCs. Application of botulinum toxin shows that the
      upregulation in tSCs and the loss of immunoreactivity in muscle fibers occurs
      with blockade of transmitter release. Extrinsic stimulation of denervated muscle
      maintains the postsynaptic expression of nestin but does not affect the
      upregulation in SCs. Thus, a nestin-containing cytoskeleton is promoted in the
      postsynaptic muscle fiber by nerve-evoked muscle activity but suppressed in tSCs
      by transmitter release. Nestin antibodies and GFP driven by nestin promoter
      elements serve as excellent markers for the reactive state of SCs. Vital imaging
      of GFP shows that SCs grow a dynamic set of processes after denervation.

PMID- 17537966
TI  - Processing of temporal unpredictability in human and animal amygdala.
AB  - The amygdala has been studied extensively for its critical role in associative
      fear conditioning in animals and humans. Noxious stimuli, such as those used for
      fear conditioning, are most effective in eliciting behavioral responses and
      amygdala activation when experienced in an unpredictable manner. Here, we show,
      using a translational approach in mice and humans, that unpredictability per se
      without interaction with motivational information is sufficient to induce
      sustained neural activity in the amygdala and to elicit anxiety-like behavior.
      Exposing mice to mere temporal unpredictability within a time series of neutral
      sound pulses in an otherwise neutral sensory environment increased expression of
      the immediate-early gene c-fos and prevented rapid habituation of single neuron
      activity in the basolateral amygdala. At the behavioral level, unpredictable, but
      not predictable, auditory stimulation induced avoidance and anxiety-like
      behavior. In humans, functional magnetic resonance imaging revealed that temporal
      unpredictably causes sustained neural activity in amygdala and anxiety-like
      behavior as quantified by enhanced attention toward emotional faces. Our findings
      show that unpredictability per se is an important feature of the sensory
      environment influencing habituation of neuronal activity in amygdala and
      emotional behavior and indicate that regulation of amygdala habituation
      represents an evolutionary-conserved mechanism for adapting behavior in
      anticipation of temporally unpredictable events.

PMID- 17537967
TI  - Epigenetic modulation of seizure-induced neurogenesis and cognitive decline.
AB  - The conceptual understanding of hippocampal function has been challenged recently
      by the finding that new granule cells are born throughout life in the mammalian
      dentate gyrus (DG). The number of newborn neurons is dynamically regulated by a
      variety of factors. Kainic acid-induced seizures, a rodent model of human
      temporal lobe epilepsy, strongly induce the proliferation of DG neurogenic
      progenitor cells and are also associated with long-term cognitive impairment. We
      show here that the antiepileptic drug valproic acid (VPA) potently blocked
      seizure-induced neurogenesis, an effect that appeared to be mainly mediated by
      inhibiting histone deacetylases (HDAC) and normalizing HDAC-dependent gene
      expression within the epileptic dentate area. Strikingly, the inhibition of
      aberrant neurogenesis protected the animals from seizure-induced cognitive
      impairment in a hippocampus-dependent learning task. We propose that seizure
      generated granule cells have the potential to interfere with hippocampal function
      and contribute to cognitive impairment caused by epileptic activity within the
      hippocampal circuitry. Furthermore, our data indicate that the effectiveness of
      VPA as an antiepileptic drug may be partially explained by the HDAC-dependent
      inhibition of aberrant neurogenesis induced by seizure activity within the adult
      hippocampus.

PMID- 17537968
TI  - Blood vessels form a scaffold for neuroblast migration in the adult olfactory
      bulb.
AB  - New cells are continuously added to the rodent olfactory bulb (OB), throughout
      development and in adults. These cells migrate tangentially from the
      subventricular zone along the rostral migratory stream to the OB, where they
      migrate radically from the center to periphery of the OB. Although different
      modalities of radial migration have been described in other brain regions, the
      mechanisms governing radial migration in the OB are still mostly unknown. Here,
      we identify a new modality of migration in which neuronal precursors migrate
      along blood vessels toward their destination. Our results show that half of the
      radially migrating cells associate with the vasculature in the granule cell layer
      of the OB, and in vivo time-lapse imaging demonstrates that they use blood
      vessels as a scaffold for their migration through an interaction with the
      extracellular matrix and perivascular astrocyte end feet. The present data
      provide evidence that a new modality of migration, vasophilic migration, is
      occurring in the adult brain and reveals a novel role of brain vasculature.

PMID- 17537969
TI  - Dissociating task performance from fMRI repetition attenuation in ventral visual
      cortex.
AB  - Repeated visual stimuli elicit reduced neural responses compared with novel
      stimuli in various brain regions (repetition attenuation). This effect has become
      a powerful tool in fMRI research, allowing researchers to investigate the
      stimulus-specific neuronal representations underlying perception and cognition.
      Repetition attenuation is also commonly associated with behavioral priming,
      whereby response accuracy and speed increase with repetition. This raises the
      possibility that repetition attenuation merely reflects decreased processing
      time. Here, we report a full dissociation between repetition attenuation and
      behavioral performance by varying the task performed on identical visual stimuli.
      In the scene task, observers judged whether two photographs came from the same
      scene, and in the image task, they judged whether the two photographs were
      identical pixel for pixel. The two tasks produced opposite patterns of behavioral
      performance: in the scene task, responses were faster and more accurate when the
      photographs were very similar, whereas, in the image task, responses were faster
      and more accurate when the photographs were less similar. However, in the
      parahippocampal place area (PPA), a scene-selective region of ventral cortex,
      identical repetition attenuation was observed in both tasks: lower neural
      responses for the very similar pairs relative to the less similar pairs. Whereas
      the PPA was impervious to task modulation, responses from two frontal regions
      mirrored behavioral performance, consistent with their role in decision-making.
      Thus, although repetition attenuation and performance are often correlated, they
      can be dissociated, suggesting that attenuation in ventral visual areas reflects
      stimulus-specific processing independent of task demands.

PMID- 17537970
TI  - A labeled-line code for small and large numerosities in the monkey prefrontal
      cortex.
AB  - How single neurons represent information about the magnitude of a stimulus
      remains controversial. Neurons encoding purely sensory magnitude typically show
      monotonic response functions ("summation coding"), and summation units are
      usually implemented in models of numerosity representation. In contrast, cells
      representing numerical quantity exhibit nonmonotonic tuning functions that peak
      at their preferred numerosity ("labeled-line code"), but the restricted range of
      tested quantities in these studies did not permit a definite answer. Here, we
      analyzed both behavioral and neuronal representations of a broad range of
      numerosities from 1 to 30 in the prefrontal cortex of monkeys. Numerosity
      selective neurons showed a clear and behaviorally relevant labeled-line code for
      all numerosities. Moreover, both the behavioral and neuronal tuning functions
      obeyed the Weber-Fechner Law and were best represented on a nonlinearly
      compressed scale. Our single-cell study is in good agreement with functional
      imaging data reporting peaked tuning functions in humans, demonstrating neuronal
      precursors for human number competence in a nonhuman primate. Our findings also
      emphasize that the manner in which neurons encode and maintain magnitude
      information may depend on the precise task at hand as well as the type of
      magnitude to represent and memorize.

PMID- 17537971
TI  - Different mechanisms generate maintained activity in ON and OFF retinal ganglion
      cells.
AB  - Neuronal discharge is driven by either synaptic input or cell-autonomous
      intrinsic pacemaker activity. It is commonly assumed that the resting spike
      activity of retinal ganglion cells (RGCs), the output cells of the retina, is
      driven synaptically, because retinal photoreceptors and second-order cells
      tonically release neurotransmitter. Here we show that ON and OFF RGCs generate
      maintained activity through different mechanisms: ON cells depend on tonic
      excitatory input to drive resting activity, whereas OFF cells continue to fire in
      the absence of synaptic input. In addition to spontaneous activity, OFF cells
      exhibit other properties of pacemaker neurons, including subthreshold
      oscillations, burst firing, and rebound excitation. Thus, variable weighting of
      synaptic mechanisms and intrinsic properties underlies differences in the
      generation of maintained activity in these parallel retinal pathways.

PMID- 17537973
TI  - Hippocampal metaplasticity induced by deficiency in the extracellular matrix
      glycoprotein tenascin-R.
AB  - Predisposition of synapses to undergo plastic changes can be dynamically adjusted
      according to the history of synaptic activity (i.e., synapses are metaplastic).
      In search of a molecular mechanism underlying metaplasticity, we investigated
      mice deficient in the glycoprotein tenascin-R (TNR), based on the observations
      that this mutant exhibits elevated basal excitatory synaptic transmission and
      reduced perisomatic GABAergic inhibition. TNR is a major extracellular matrix
      glycoprotein of the CNS and carries the HNK-1 carbohydrate (human natural killer
      cell glycan), which has been identified as the functional epitope mediating
      regulation of GABAergic transmission via GABA(B) receptors. Here, we used patch
      clamp recordings in hippocampal slices to determine the critical levels of
      postsynaptic neuron depolarization necessary for induction of long-term
      potentiation (LTP) at CA3-CA1 synapses and found that deficiency in TNR leads to
      a metaplastic increase in the threshold for induction of LTP. Reconstitution of
      slices from TNR-deficient mice with an HNK-1 glycomimetic or pharmacological
      treatment with either a GABA(A) receptor agonist, a GABA(B) receptor antagonist,
      an L-type voltage-dependent Ca2+ channel blocker, or an inhibitor of protein
      serine/threonine phosphatases restored LTP to the levels seen in wild-type mice.
      We propose that a chain of events initiated by reduced GABAergic transmission and
      proceeding via Ca2+ entry into cells and elevated activity of phosphatases
      mediates homeostatic adjustment of hippocampal plasticity in the absence of TNR.
      These data uncover a novel mechanism by which an extracellular matrix molecule
      and its associated carbohydrate provide conditions beneficial for induction of
      LTP in the CA1 region of the hippocampus.

PMID- 17537972
TI  - Glial-cytokine-neuronal interactions underlying the mechanisms of persistent
      pain.
AB  - The emerging literature implicates a role for glia/cytokines in persistent pain.
      However, the mechanisms by which these non-neural elements contribute to CNS
      activity-dependent plasticity and pain are unclear. Using a trigeminal model of
      inflammatory hyperalgesia, here we provide evidence that demonstrates a mechanism
      by which glia interact with neurons, leading to activity-dependent plasticity and
      hyperalgesia. In response to masseter inflammation, there was an upregulation of
      glial fibrillary acidic proteins (GFAPs), a marker of astroglia, and interleukin
      1beta (IL-1beta), a prototype proinflammatory cytokine, in the region of the
      trigeminal nucleus specifically related to the processing of deep orofacial
      input. The activated astroglia exhibited hypertrophy and an increased level of
      connexin 43, an astroglial gap junction protein. The upregulated IL-1beta was
      selectively localized to astrocytes but not to microglia and neurons. Local
      anesthesia of the masseter nerve prevented the increase in GFAP and IL-1beta
      after inflammation, and substance P, a prototype neurotransmitter of primary
      afferents, induced similar increases in GFAP and IL-1beta, which was blocked by a
      nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester. Injection of
      IL-1 receptor antagonist and fluorocitrate, a glial inhibitor, attenuated
      hyperalgesia and NMDA receptor phosphorylation after inflammation. In vitro
      application of IL-1beta induced NR1 phosphorylation, which was blocked by an IL-1
      receptor antagonist, a PKC inhibitor (chelerythrine), an IP3 receptor inhibitor
      (2-aminoethoxydiphenylborate), and inhibitors of phospholipase C [1-[6-((17b-3
      methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl]-1H-pyrrole-2,5-dione] and
      phospholipase A2 (arachidonyltrifluoromethyl ketone). These findings provide
      evidence of astroglial activation by tissue injury, concomitant IL-1beta
      induction, and the coupling of NMDA receptor phosphorylation through IL-1
      receptor signaling.

PMID- 17537974
TI  - Involvement of the basal ganglia and cerebellar motor pathways in the preparation
      of self-initiated and externally triggered movements in humans.
AB  - The subthalamic nucleus (STN) is part of the cortico-basal ganglia (BG)
      thalamocortical circuit, whereas the ventral lateral nucleus of the thalamus (VL)
      is a relay nucleus in the cerebello-dentato-thalamocortical (CTC) pathway. Both
      pathways have been implicated in movement preparation. We compared the
      involvement of the STN and VL in movement preparation in humans by recording
      local field potentials (LFPs) from seven patients with Parkinson's disease with
      deep-brain stimulation (DBS) electrodes in the STN and five patients with tremor
      and electrodes in VL. LFPs were recorded from DBS electrodes and scalp electrodes
      simultaneously while the patients performed self-paced and externally cued
      (ready, go/no-go) movements. For the self-paced movement, a premovement-related
      potential was observed in all patients from scalp, STN (phase reversal, five of
      six patients), and VL (phase reversal, five of five patients) electrodes. The
      onset times of the potentials were similar in the cortex, STN, and VL, ranging
      from 1.5 to 2 s before electromyogram onset. For the externally cued movement, an
      expectancy potential was observed in all patients in cortical and STN electrodes
      (phase reversal, six of six patients). The expectancy potential was recorded from
      the thalamic electrodes in four of five patients. However, phase reversal
      occurred only in one case, and magnetic resonance imaging showed that this
      contact was outside the VL. The cortico-BG-thalamocortical circuit is involved in
      the preparation of both self-paced and externally cued movements. The CTC pathway
      is involved in the preparation of self-paced but not externally cued movements,
      although the pathway may still be involved in the execution of these movements.

PMID- 17537975
TI  - Learning-induced survival of new neurons depends on the cognitive status of aged
      rats.
AB  - Aging is accompanied by an alteration of spatial memory, which has been related
      to an alteration in hippocampal plasticity. Within the dentate gyrus, new neurons
      are generated throughout the entire life of an individual. This neurogenesis
      seems to play a role in hippocampal-mediated learning and learning-induced
      changes in neurogenesis have been proposed to be involved in memory. However, in
      aged rats, little is known on the influence of learning on the early development
      of the adult-born neurons and on the possible involvement of learning-induced
      changes in neurogenesis in age-related memory deficits. To address this issue, we
      took advantage of the existence of spontaneous individual differences for
      performances observed in aged subjects in the water maze. In this task, learning
      can be divided into two phases, an early phase during which performances quickly
      improve, and a late phase during which asymptotic levels of performances are
      reached. We show that the influence of spatial learning on the survival of the
      newly born cells depends on their birth date and the memory abilities of the aged
      rats. In aged rats with preserved spatial memory, learning increases the survival
      of cells generated before learning whereas it decreases survival of cells
      produced during the early phase of learning. These results highlight the
      importance of learning-induced changes in adult-born cell survival in memory.
      Furthermore, they provide new insights on the possible neural mechanisms of aging
      of cognitive functions and show that an alteration to the steps leading to
      neurogenesis may be involved in the determination of individual memory abilities.

PMID- 17537976
TI  - Mice lacking central serotonergic neurons show enhanced inflammatory pain and an
      impaired analgesic response to antidepressant drugs.
AB  - A large body of literature has implicated serotonin [5-hydroxytryptamine (5-HT)]
      in descending modulation of nociceptive transmission. Here, we have studied the
      pain behavior of Lmx1b conditional knock-out mice (Lmx1b(f/f/p)), which lack 5-HT
      neurons in the CNS. Lmx1b(f/f/p) mutant mice showed normal thermal and visceral
      pain responses but were less sensitive to mechanical stimuli and exhibited
      enhanced inflammatory pain compared with their littermate control mice.
      Importantly, the analgesic effect of several antidepressant drugs, including
      selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine
      reuptake inhibitors (SNRIs), and tricyclic antidepressants, was either abolished
      or greatly attenuated in Lmx1b(f/f/p) mice. Moreover, in the acute versus
      persistent pain settings, the analgesic actions of the SNRI duloxetine and the
      SSRI fluoxetine were differentially affected. Together, our results provide in
      vivo genetic evidence demonstrating that although the predominant role of the
      central 5-HT system in inflammatory pain is inhibitory, its role in acute
      mechanical pain is facilitatory. The findings that the analgesic effects of
      various antidepressant drugs are differentially dependent on the central 5-HT
      system should help us to understand the mechanism of the analgesic action of
      different classes of antidepressants in the management of persistent pain.

PMID- 17537977
TI  - Beta-estradiol increases dentate gyrus inhibition in female rats via augmentation
      of hilar neuropeptide Y.
AB  - The dentate gyrus filters incoming activity into the hippocampus proper. It plays
      a role in learning and memory and in pathological states such as epilepsy. Some
      of hilar interneurons of the dentate gyrus express neuropeptide Y (NPY), which
      modulates granule cell activity. A subpopulation of the NPY-expressing inhibitory
      interneurons is sensitive to seizure-induced damage. Pretreatment with beta
      estradiol in ovariectomized rats protects hilar interneurons against seizure
      induced injury, including the NPY-containing damage-sensitive subpopulation.
      Here, we demonstrate that beta-estradiol enhances NPY expression within the hilar
      interneurons. In vitro paired-pulse stimulation of the mixed perforant path
      revealed beta-estradiol-induced augmentation of granule cell network inhibition,
      which at interstimulus intervals between 200 and 300 ms (corresponding to
      approximately 3-5 Hz) was NPY sensitive and involved Y1 receptors, whereas it was
      insensitive to GABA(B) or metabotropic glutamate receptor antagonists.
      Additionally, beta-estradiol pretreatment attenuated propagation of low-frequency
      (3.3 or 5 Hz) burst activity through the dentate gyrus. Scavenging endogenous NPY
      by intracerebroventricular administration of anti-NPY antibody accelerated kainic
      acid-induced seizure onset and increased seizure-induced neuronal damage in the
      hilus compared with rats treated with beta-estradiol alone. Together, we show
      that beta-estradiol upregulates hilar NPY and that this leads to enhancement in
      dentate gyrus inhibition of incoming frequencies between 3 and 5 Hz. Such
      frequencies are similar to the discharge frequencies recorded during seizure
      initiation in some patients with epilepsy. Thus, beta-estradiol-induced NPY
      sensitive filtering of 3-5 Hz frequencies may be an important regulator of
      incoming seizure activity, but it could also serve a physiological purpose in
      modulating information flow into the hippocampus proper.

PMID- 17537978
TI  - Rapid synapse elimination after postsynaptic protein synthesis inhibition in
      vivo.
AB  - To examine the role of retrograde signals on synaptic maintenance, we inhibited
      protein synthesis in individual postsynaptic cells in vivo while monitoring
      presynaptic terminals. Within 12 h, axon terminals begin to atrophy and withdraw
      from normal postsynaptic sites. Structural similarities between this process and
      naturally occurring synapse elimination suggest that short-lived target derived
      factors not only participate in synaptic maintenance in adults, but also regulate
      elimination of connections during development.

PMID- 17537979
TI  - Targeting sensory axon regeneration in adult spinal cord.
AB  - Extensive regeneration of sensory axons into the spinal cord can be achieved
      experimentally after dorsal root injury, but no effort has been made to target
      regenerating axons and restore a normal lamina-specific projection pattern.
      Ectopic axon growth is potentially associated with functional disorders such as
      chronic pain and autonomic dysreflexia. This study was designed to target
      regenerating axons to normal synaptic locations in the spinal cord by combining
      positive and negative guidance molecules. Previously, we observed that, after
      dorsal rhizotomy, overexpression of NGF leads to robust regeneration and
      sprouting of calcitonin gene-related peptide (CGRP)-positive nociceptive axons
      throughout dorsal horn and ventral horns. To restrict these axons within
      superficial laminas, adenovirus expressing semaphorin 3A was injected into the
      ventral spinal cord 3 d after NGF virus injection. Semaphorin 3A expression was
      observed in deep dorsal and ventral cord regions and limited axon growth to
      laminas I and II, shaping axonal regeneration toward the normal distribution
      pattern. NGF and semaphorin 3A treatment also targeted the regeneration of
      substance P-positive nociceptive axons but had no effect on injured isolectin B4
      binding nociceptive axons. Axon regeneration led to functional restoration of
      nociception in both NGF- and NGF/semaphorin 3A-treated rats. Although no
      significant difference in behavior was found between these two groups, confocal
      microscopy illustrated ectopic synaptic formations in deeper laminas in NGF/green
      fluorescent protein-treated rats. The results suggested that antagonistic
      guidance cues can be used to induce and refine regeneration within the CNS, which
      is important for long-term, optimal functional recovery.

PMID- 17537980
TI  - Extracellular calcium-sensing receptor is functionally expressed in human artery.
AB  - Accelerated medial calcification is a major cause of premature cardiovascular
      mortality in patients with chronic kidney disease (CKD). Evidence suggests that
      extracellular concentration of Ca2+ and vascular smooth muscle cells may play a
      pivotal role in the pathogenesis of vascular calcification. The calcium-sensing
      receptor (CaSR) is a G protein-coupled receptor that is expressed in a range of
      tissues, but characterization of its expression and function in the
      cardiovascular system is limited. Here we report the expression of CaSR mRNA (RT
      PCR) and protein (Western blotting and immunocytochemistry) in human aortic
      smooth muscle cells (HAoSMC). Treatment of HAoSMC with Ca2+ (0-5 mM; 0-30 min) or
      the CaSR agonists gentamycin and neomycin (0-300 microM; 0-30 min) resulted in a
      dose- and time-dependent phosphorylation of ERK1/2. Gentamycin- and neomycin
      mediated ERK1/2 stimulation was inhibited by pretreatment with PD-98059, an ERK
      activating kinase 1 (MEK1) inhibitor, confirming specificity of the observed
      effects. ERK1/2 activation was inhibited in HAoSMC, with CaSR expression knocked
      down by transfection with specific small-interference RNA, which confirmed that
      the observed neomycin/gentamycin-induced MEK1/ERK1/2 activation was mediated via
      the CaSR. CaSR mRNA and protein were also expressed in large and small arteries
      from normal subjects (kidney donors) and patients with end-stage renal disease
      (ESRD). The CaSR was detected in smooth muscle and endothelial cells. Expression
      was significantly lower in arteries from ESRD patients. In conclusion, these data
      not only demonstrate the presence of a functional CaSR in human artery but show a
      correlation between CaSR expression and progression of CKD.

PMID- 17537981
TI  - Selective COX-2 inhibition markedly slows disease progression and attenuates
      altered prostanoid production in Han:SPRD-cy rats with inherited kidney disease.
AB  - Selective cyclooxygenase-2 (COX-2) inhibitors appear to have beneficial
      renoprotective effects in most, but not all, renal disease conditions. The
      objective of our study was to examine the effects of COX-2 inhibition in a rat
      model of polycystic kidney disease. Four-week-old Han:SPRD-cy rats were given a
      standard rodent diet containing NS-398 (3 mg.kg body wt(-1).day(-1)) or a control
      diet without NS-398 for 7 wk. In diseased rats, selective COX-2 inhibition
      resulted in 18% and 67% reduction in cystic expansion and interstitial fibrosis,
      respectively, but no change in renal function. NS-398 also ameliorated disease
      associated pathologies, such as renal inflammation, cell proliferation, and
      oxidant injury (by 33, 38, and 59%, respectively). Kidney disease was associated
      with elevated renal COX-1 and COX-2 enzyme activities, and NS-398 blunted the
      increase in COX-2 enzyme activity (as indicated by 21 and 28% lower renal
      thromboxane B2 and PGE2 levels, respectively). NS-398 reduced urinary excretion
      of prostanoid metabolites in diseased rats. In summary, COX-2 inhibition
      attenuated renal injury, reduced the elevated renal COX-2 activity, and
      ameliorated disease-related alterations in prostanoid production in this rat
      model of chronic renal disease.

PMID- 17537982
TI  - Functional duality of progenitor cells influxing into arteriovenous fistula
      during its neoangiogenesis.

PMID- 17537983
TI  - Testosterone regulation of renal cystathionine beta-synthase: implications for
      sex-dependent differences in plasma homocysteine levels.
AB  - Elevated plasma total homocysteine (tHcy) is an independent risk factor for
      ischemic heart disease and stroke. Epidemiological studies reveal that men have
      higher tHcy levels than women, but the mechanism underlying this sex-dependent
      difference is unknown. One route for intracellular disposal of homocysteine is
      catalyzed by cystathionine beta-synthase (CBS). Renal function is known to be an
      important determinant of tHcy, and, in this study, we demonstrate that renal CBS
      expression and activity in mice diminished approximately twofold after
      castration, whereas ovariectomization was without effect. The higher renal CBS
      activity in males (22.7 +/- 3.1 mmol cystathionine.h(-1).kg kidney(-1)) vs.
      females (8.4 +/- 3.4 mmol cystathionine.h(-1).kg kidney(-1), P < or = 10(-6)) in
      C57Bl/6J mice was associated with lower plasma tHcy levels in males vs. females,
      and this difference was exacerbated in Cbs+/- mice (7.7 +/- 1.9 micromol/l in
      males vs. 13.8 +/- 6.4 micromol/l in females, P = 0.005). Surprisingly, mammals
      exhibit a diversity of regulatory patterns for kidney CBS, with females
      exhibiting lower CBS activity in mice, higher in rats and humans, and being
      indistinguishable from males in rabbit, hamster, and guinea pig. Our data suggest
      that testosterone-dependent regulation of human CBS in kidney may contribute to
      sex-dependent differences in homocysteine transsulfuration.

PMID- 17537984
TI  - Effects of dexamethasone exposure on rat metanephric development: in vitro and in
      vivo studies.
AB  - Maternal administration of dexamethasone (DEX) for 48 h early in rat kidney
      development results in offspring with a reduced nephron endowment. However, the
      mechanism through which DEX inhibits nephrogenesis is unknown. In this study, we
      hypothesized that DEX may indirectly inhibit nephrogenesis by inhibiting ureteric
      branching morphogenesis. Whole metanephroi from embryonic day 14.5 (E14.5) rat
      embryos were cultured in the presence of DEX. DEX (10(-5) M) exposure for 2 days
      significantly inhibited ureteric branching compared with metanephroi grown in
      control media or DEX (10(-7) M). Culturing metanephroi for a further 3 days (in
      control media only) reduced total glomerular number in metanephroi previously
      exposed to DEX (10(-5) M) or (10(-7) M) compared with control cultures.
      Expression of genes known to regulate ureteric branching morphogenesis was
      determined by real-time PCR in metanephroi after 2 days in culture. DEX exposure
      in vitro decreased expression of glial cell line-derived neurotrophic factor
      (GDNF) and increased expression of bone morphogenetic protein-4 (BMP-4) and
      transforming growth factor-beta1 (TGF-beta1). Similar gene expression changes
      were found in E16.5 metanephroi in which the dam had been exposed to 2 days of
      DEX (0.2 mg.kg(-1).day(-1)) at E14.5/15.5 in vivo. However, in kidneys collected
      at E20.5 after in vivo exposure for 2 days, GDNF expression was increased and BMP
      4 and TGF-beta1 expression decreased suggesting a biphasic response in gene
      expression to DEX exposure. These results show for the first time that inhibition
      of ureteric branching morphogenesis may be a key mechanism through which DEX
      exposure results in a reduced nephron endowment.

PMID- 17537985
TI  - Atherogenic scavenger receptor modulation in the tubulointerstitium in response
      to chronic renal injury.
AB  - Oxidized low-density lipoproteins (oxLDL) and their scavenger receptor (SR)
      binding partners play a central role in atherosclerosis and by analogy may play a
      role in chronic kidney disease pathogenesis. The present study was designed to
      investigate in C57BL/6 mice the effects of hypercholesterolemia on renal injury
      severity and oxLDL generation after unilateral ureteral obstruction (UUO). The
      expression profiles of CD36, SR class AI/II (SR-A), lectin-like receptor for
      oxidized low-density lipoprotein-1 (Lox-1), and SR that binds phosphatidylserine
      and oxLDL (SR-PSOX/CXCL16) were examined. Four experimental groups were studied:
      sham and UUO male mice on either a high-fat Western diet or a control diet.
      Significantly more oxLDL accumulated in the tubulointerstitium of
      hypercholesterolemic mice compared with normocholesterolemic mice after 14 days
      of UUO (P < 0.01). Total kidney collagen was significantly higher in the
      obstructed kidneys of hypercholesterolemic mice compared with
      normocholesterolemic mice on day 14 (P < 0.01). After 14 days of obstruction, the
      number of interstitial F4/80+ macrophages and NF-kappaB activation increased in
      hypercholesterolemic mice compared with normocholesterolemic mice (P < 0.01). In
      normal kidneys, CD36, SR-A, Lox-1, and CXCL16 were primarily localized to renal
      tubular epithelia. After ureteral obstruction, CD36 increased at day 7; SR-A and
      Lox-1 progressively decreased in a time-dependent manner; and CXCL16 increased
      significantly with the onset of obstruction (P < 0.01). Strong tubular expression
      suggests that in addition to inflammatory interstitial cells, renal tubular
      scavenger receptors may help to orchestrate the inflammatory and fibrogenic
      pathways that are activated by oxLDL.

PMID- 17537986
TI  - Genetic deletion of AT1a receptors attenuates intracellular accumulation of ANG
      II in the kidney of AT1a receptor-deficient mice.
AB  - We and others have previously shown that high levels of ANG II are accumulated in
      the rat kidney via a type 1 (AT(1)) receptor-mediated mechanism, but it is not
      known which AT(1) receptor is involved in this process in rodents. We tested the
      hypothesis that AT(1a) receptor-deficient mice (Agtr1a-/-) are unable to
      accumulate ANG II intracellularly in the kidney because of the absence of AT(1a)
      receptor-mediated endocytosis. Adult male wild-type (Agtr1a+/+), heterozygous
      (Agtr1a+/-), and Agtr1a-/- were treated with vehicle, ANG II (40 ng/min ip via
      osmotic minipump), or ANG II plus the AT(1) antagonist losartan (10 mg.kg(
      1).day(-1) po) for 2 wk. In wild-type mice, ANG II induced hypertension (168 +/-
      4 vs. 113 +/- 3 mmHg, P < 0.001), increased kidney-to-body weight ratio (P <
      0.01), caused pressure natriuresis (P < 0.05), and elevated plasma and whole
      kidney ANG II levels (P < 0.001). Concurrent administration of ANG II with
      losartan attenuated these responses to ANG II. In contrast, Agtr1a-/- mice had
      lower basal systolic pressures (P < 0.001), smaller kidneys with much fewer
      AT(1b) receptors (P < 0.001), higher basal 24-h urinary sodium excretion (P <
      0.01), as well as basal plasma and whole kidney ANG II levels (P < 0.01).
      However, intracellular ANG II levels in the kidney were lower in Agtr1a-/- mice.
      In Agtr1a-/- mice, ANG II slightly increased systolic pressure (P < 0.05) but had
      no effect on the kidney weight, urinary sodium excretion, and whole kidney ANG II
      levels. Losartan restored systolic pressure to basal levels and decreased whole
      kidney ANG II levels by approximately 20% (P < 0.05). These results demonstrate a
      predominant role of AT(1a) receptors in blood pressure regulation and in the
      renal responses to long-term ANG II administration, that AT(1b) receptors may
      play a limited role in blood pressure control and mediating intrarenal ANG II
      accumulation in the absence of AT(1a) receptors.

PMID- 17537987
TI  - Evaluation of no-wash calcium assay kits: enabling tools for calcium
      mobilization.
AB  - The no-wash calcium assay kits developed by Molecular Devices Corporation have
      greatly enhanced the throughput of cell-based calcium mobilization high
      throughput screening (HTS) assays and enabled screening using nonadherent cells.
      The fluorescent imaging plate reader (FLIPR) Calcium 3 Assay Kit, optimal for
      targets that have proteins or peptides as agonists, has 2 potential drawbacks: 1)
      a significant downward spike in fluorescence signal upon liquid transfer that can
      be the same magnitude as the agonist response, making data analysis difficult;
      and 2) medium removal is required for some targets, which essentially
      reintroduces a wash step. Several no-wash products were introduced in 2005. The
      authors compare the Fluo-4 NW Calcium Assay Kit and the BD Calcium Assay Kit with
      the FLIPR Calcium 3 Assay Kit using human native rhabdomyosarcoma cells
      expressing the urotensin-II receptor (UT). The BDtrade mark Calcium Assay Kit
      gives the best performance in the true no-wash mode, in which both agonist and
      antagonist activity are easily quantified. Although these new products provide
      additional options for measuring calcium mobilization, the different results
      observed with each kit, using the UT receptor as an example, suggest that one
      should characterize all dyes against each target in a systematic way prior to
      choosing one for HTS.

PMID- 17537988
TI  - Role of NF-kappaB in transcriptional regulation of the phagocyte NADPH oxidase by
      tumor necrosis factor-alpha.
AB  - Macrophages play an important role in the pathogenesis of chronic inflammatory
      disease. Activation of these phagocytes induces the production of proinflammatory
      cytokines, such as IL-1 and TNF-alpha and the generation of reactive oxygen
      species (ROS), such as superoxide anion (O2*-). Recently, we found that TNF-alpha
      treatment of human monocytic cells (MonoMac1) and isolated human monocytes
      resulted in up-regulation of the NADPH oxidase gene, neutrophil cytosolic factor
      2 (NCF2). These results suggested that TNF-alpha, produced by activated
      macrophages, could serve as an autocrine/paracrine regulator of the oxidase,
      resulting in increased and/or prolonged production of O2*-. To gain a better
      understanding of the mechanisms involved in NADPH oxidase regulation by TNF
      alpha, we evaluated transcriptional regulation of oxidase genes in MonoMac1 cells
      and human monocytes. We show that TNF-alpha-treated cells have increased levels
      of mRNA and up-regulated expression of NADPH oxidase subunits p47(phox),
      p67(phox), and gp91(phox), as well as increased oxidase activity. Pharmacological
      inhibitors of NF-kappaB activation blocked TNF-alpha-induced up-regulation of
      NCF1, NCF2, and CYBB message, which correlated with a reduction in expression of
      the corresponding oxidase proteins and decreased O2*- production. These data
      demonstrate that the increase in and/or maintenance of O2*- production in TNF
      alpha-treated MonoMac1 cells and monocytes are a result, in part, of
      transcriptional up-regulation of three essential NADPH oxidase genes via the NF
      kappaB pathway. This novel finding supports a model, whereby TNF-alpha-dependent
      activation of NF-kappaB up-regulates phagocyte NADPH oxidase activity, leading to
      enhanced ROS production and further NF-kappaB activation, potentially
      contributing to sustained oxidant production in chronic inflammation.

PMID- 17537989
TI  - Anti-inflammatory property of the cannabinoid receptor-2-selective agonist JWH
      133 in a rodent model of autoimmune uveoretinitis.
AB  - Previous studies have shown that cannabinoids have anti-inflammatory and immune
      modulating effects, but the precise mechanisms of action remain to be elucidated.
      In this study, we investigated the effect of JWH 133, a selective agonist for
      cannabinoid receptor 2, the main receptor expressed on immune cells, in a model
      of autoimmune disease, experimental autoimmune uveoretinitis (EAU). JWH 133
      suppressed EAU in a dose-dependent manner (0.015-15 mg/kg), and the suppressive
      effect could be achieved in the disease-induction stage and the effector stage.
      Leukocytes from mice, which had been treated with JWH 133, had diminished
      responses to retinal peptide and mitogen Con A stimulation in vitro. In vivo JWH
      133 treatment also abrogated leukocyte cytokine/chemokine production. Further in
      vitro studies indicated that JWH 133 down-regulated the TLR4 via Myd88 signal
      transduction, which may be responsible for its moderate, suppressive effect on
      antigen presentation. In vivo JWH 133 treatment (1 mg/kg) also suppressed
      leukocyte trafficking (rolling and infiltration) in inflamed retina as a result
      of an effect on reducing adhesion molecules CD162 (P-selectin glycoprotein ligand
      1) and CD11a (LFA-1) expression on T cells. In conclusion, the cannabinoid
      agonist JWH 133 has a high in vivo, anti-inflammatory property and may exert its
      effect via inhibiting the activation and function of autoreactive T cells and
      preventing leukocyte trafficking into the inflamed tissue.

PMID- 17537990
TI  - p52Shc is required for CXCR4-dependent signaling and chemotaxis in T cells.
AB  - ShcA is an important mediator of Ras/MAPK activation in PTK-regulated pathways
      triggered by surface receptors. This function is subserved by the constitutively
      expressed p52-kDa isoform. Besides activating Ras, p52Shc couples the TCR to Rho
      GTPases, and thereby participates in actin cytoskeleton remodeling in T cells.
      Here we have addressed the potential involvement of p52Shc in T-cell chemotaxis
      and the role of the phosphorylatable tyrosine residues, YY239/240 and Y317, in
      this process. We show that CXCR4 engagement by the homeostatic chemokine, SDF
      1alpha, results in p52Shc phosphorylation and its assembly into a complex that
      includes Lck, ZAP-70, and Vav. This process was found to be both Lck and Gi
      dependent. Expression of p52Shc mutants lacking YY239/240 or Y317, or p52Shc
      deficiency, resulted in a profound impairment in CXCR4 signaling and SDF-1alpha
      dependent chemotaxis, underscoring a crucial role of p52Shc as an early component
      of the CXCR4 signaling cascade. p52Shc was also found to be required for ligand
      dependent CXCR4 internalization independently of tyrosine phosphorylation.
      Remarkably, CXCR4 engagement promoted phosphorylation of the zeta chain of the
      TCR/CD3 complex, which was found to be essential for CXCR4 signaling, as well as
      for SDF-1alpha-dependent receptor endocytosis and chemotaxis, indicating that
      CXCR4 signals by transactivating the TCR.

PMID- 17537991
TI  - The low-molecular-weight phosphotyrosine phosphatase is a negative regulator of
      FcgammaRIIA-mediated cell activation.
AB  - Activation of human platelets by cross-linking of the low-affinity receptor for
      immunoglobulin G (FcgammaRIIA) is initiated by Src kinase-mediated
      phosphorylation of the immunoreceptor tyrosine-based activation motif (ITAM)
      within the receptor, but the identity of the enzyme responsible for its
      dephosphorylation and inactivation is unknown. Here we report that the 18-kDa low
      molecular-weight phosphotyrosine phosphatase (LMW-PTP) is expressed in human
      platelets and undergoes subcellular redistribution upon FcgammaRIIA cross
      linking. In vitro, LMW-PTP was found to efficiently dephosphorylate activated
      FcgammaRIIA and LAT, but not Syk or phospholipase Cgamma2. In the megakaryocytic
      cell line DAMI, antibody-induced phosphorylation of FcgammaRIIA was rapid and
      transient. The late dephosphorylation of FcgammaRIIA was dramatically delayed
      upon reduction of LMW-PTP expression by siRNA. Strikingly, overexpression of LMW
      PTP resulted in the inhibition of antibody-induced phosphorylation of
      FcgammaRIIA, and caused a more rapid dephosphorylation. In addition,
      overexpression of LMW-PTP inhibited activation of Syk downstream of FcgammaRIIA
      and reduced intracellular Ca(2+) mobilization. These results demonstrate that LMW
      PTP is responsible for FcgammaRIIA dephosphorylation, and is implicated in the
      down-regulation of cell activation mediated by this ITAM-bearing immunoreceptor.

PMID- 17537992
TI  - 2B4 inhibits NK-cell fratricide.
AB  - 2B4 (CD244) and its ligand, CD48, are expressed on all natural killer (NK) cells.
      In studies using 2B4-deficient, CD48-deficient, or wild-type NK cells with
      blocking antibodies, we found that in the absence of 2B4-CD48 interactions,
      activated murine NK cells kill each other. We also show that NK-NK fratricide in
      the absence of 2B4-CD48 interaction is dependent on perforin both in vitro and in
      vivo. 2B4 has been reported to have activating, costimulatory, and inhibitory
      functions on murine NK cells. 2B4-mediated inhibition of NK-cell fratricide
      explains some of the paradoxes of 2B4 function reported in studies of murine NK
      cells. We show that in the absence of 2B4 signaling, activated NK cells have
      defective cytotoxicity and proliferation because of fratricide and not due to the
      absence of a 2B4-dependent activation signal.

PMID- 17537993
TI  - Pharmacologic inhibition of CDK4/6: mechanistic evidence for selective activity
      or acquired resistance in acute myeloid leukemia.
AB  - Entry into the cell cycle is mediated by cyclin-dependent kinase 4/6 (CDK4/6)
      activation, followed by CDK2 activation. We found that pharmacologic inhibition
      of the Flt3 internal tandem duplication (ITD), a mutated receptor tyrosine kinase
      commonly found in patients with acute myelogenous leukemia (AML), led to the down
      regulation of cyclin D2 and D3 followed by retinoblastoma protein (pRb)
      dephosphorylation and G(1) cell-cycle arrest. This implicated the D-cyclin-CDK4/6
      complex as a downstream effector of Flt3 ITD signaling. Indeed, single-agent
      PD0332991, a selective CDK4/6 inhibitor, caused sustained cell-cycle arrest in
      Flt3 ITD AML cell lines and prolonged survival in an in vivo model of Flt3 ITD
      AML. PD0332991 caused an initial cell-cycle arrest in well-established Flt3 wild
      type (wt) AML cell lines, but this was overcome by down-regulation of p27(Kip)
      and reactivation of CDK2. This acquired resistance was not observed in a Flt3 ITD
      and a Flt3 wt sample from a patient with primary AML. In summary, the mechanism
      of cell-cycle arrest after treatment of Flt3 ITD AML with a Flt3 inhibitor
      involves down-regulation of cyclin D2 and D3. As such, CDK4/6 can be a
      therapeutic target in Flt3 ITD AML but also in primary Flt3 wt AML. Finally,
      acquired resistance to CDK4/6 inhibition can arise through activation CDK2.

PMID- 17537994
TI  - Mosaicism due to myeloid lineage restricted loss of heterozygosity as cause of
      spontaneous Rh phenotype splitting.
AB  - Spontaneous Rh phenotype alteration interferes with pretransfusion and prenatal
      blood group examinations and may potentially indicate hematologic disease. In
      this study, the molecular background of this biologic phenomenon was
      investigated. In 9 patients (3 with hematologic disease), routine RhD typing
      showed a mixture of D-positive and D-negative red cells not attributable to
      transfusion or hematopoietic stem-cell transplantation. In all patients,
      congenital and acquired chimerism was excluded by microsatellite analysis. In
      contrast to D-positive red cells, D-negative subpopulations were also negative
      for C or E in patients genotyped CcDdee or ccDdEe, respectively, which suggested
      the presence of erythrocyte precursors with an apparent homozygous cde/cde or
      hemizygous cde/- genotype. Except for one patient with additional Fy(b) antigen
      anomaly, no other blood group systems were affected. RH genotyping of single
      erythropoietic burst-forming units, combined with microsatellite analysis of
      blood, different tissues, sorted blood cell subsets, and erythropoietic burst
      forming units, indicated myeloid lineage-restricted loss of heterozygosity (LOH)
      of variable chromosome 1 stretches encompassing the RHD/RHCE gene loci.
      Fluorescent in situ hybridization studies indicated that LOH was caused by either
      somatic recombination or deletion. Therefore, most cases of spontaneous Rh
      phenotype splitting appear to be due to hematopoietic mosaicism based on LOH on
      chromosome 1.

PMID- 17537996
TI  - Low-dose arsenic trioxide sensitizes glucocorticoid-resistant acute lymphoblastic
      leukemia cells to dexamethasone via an Akt-dependent pathway.
AB  - Incorporation of apoptosis-inducing agents into current therapeutic regimens is
      an attractive strategy to improve treatment for drug-resistant leukemia. We
      tested the potential of arsenic trioxide (ATO) to restore the response to
      dexamethasone in glucocorticoid (GC)-resistant acute lymphoblastic leukemia
      (ALL). Low-dose ATO markedly increased in vitro GC sensitivity of ALL cells from
      T-cell and precursor B-cell ALL patients with poor in vivo response to
      prednisone. In GC-resistant cell lines, this effect was mediated, at least in
      part, by inhibition of Akt and affecting downstream Akt targets such as Bad, a
      proapoptotic Bcl-2 family member, and the X-linked inhibitor of apoptosis protein
      (XIAP). Combination of ATO and dexamethasone resulted in increased Bad and rapid
      down-regulation of XIAP, while levels of the antiapoptotic regulator Mcl-1
      remained unchanged. Expression of dominant-active Akt, reduction of Bad
      expression by RNA interference, or overexpression of XIAP abrogated the
      sensitizing effect of ATO. The inhibitory effect of XIAP overexpression was
      reduced when the Akt phosphorylation site was mutated (XIAP-S87A). These data
      suggest that the combination of ATO and glucocorticoids could be advantageous in
      GC-resistant ALL and reveal additional targets for the evaluation of new
      antileukemic agents.

PMID- 17537995
TI  - NPM/ALK binds and phosphorylates the RNA/DNA-binding protein PSF in anaplastic
      large-cell lymphoma.
AB  - The oncogenic fusion tyrosine kinase nucleophosmin/anaplastic lymphoma kinase
      (NPM/ALK) induces cellular transformation in anaplastic large-cell lymphomas
      (ALCLs) carrying the t(2;5) chromosomal translocation. Protein-protein
      interactions involving NPM/ALK are important for the activation of downstream
      signaling pathways. This study was aimed at identifying novel NPM/ALK-binding
      proteins that might contribute to its oncogenic transformation. Using a proteomic
      approach, several RNA/DNA-binding proteins were found to coimmunoprecipitate with
      NPM/ALK, including the multifunctional polypyrimidine tract binding
      proteinassociated splicing factor (PSF). The interaction between NPM/ALK and PSF
      was dependent on an active ALK kinase domain and PSF was found to be tyrosine
      phosphorylated in NPM/ALK-expressing cell lines and in primary ALK(+) ALCL
      samples. Furthermore, PSF was shown to be a direct substrate of purified ALK
      kinase domain in vitro, and PSF Tyr293 was identified as the site of
      phosphorylation. Y293F PSF was not phosphorylated by NPM/ALK and was not
      delocalized in NPM/ALK(+) cells. The expression of ALK fusion proteins induced
      delocalization of PSF from the nucleus to the cytoplasm and forced overexpression
      of PSF-inhibited proliferation and induced apoptosis in cells expressing NPM/ALK.
      PSF phosphorylation also increased its binding to RNA and decreased the PSF
      mediated suppression of GAGE6 expression. These results identify PSF as a novel
      NPM/ALK-binding protein and substrate, and suggest that PSF function may be
      perturbed in NPM/ALK-transformed cells.

PMID- 17537997
TI  - Hepatotoxicity during nevirapine-based fixed-dose combination antiretroviral
      therapy in kampala, Uganda.
AB  - BACKGROUND: Generic, low-cost, nevirapine (NVP)-based antiretroviral therapy
      (ART) has improved survival in HIV-infected individuals living in resource
      limited settings. However, there is concern about the potential hepatotoxicity of
      these regimens. METHODS: The authors conducted a prospective study of persons
      initiating self-pay Triomune or Maxivir therapy in Kampala, Uganda. RESULTS: The
      97 study participants were predominantly women (64%), median age was 35
      (interquartile range [IQR] 30-40), median CD4 at baseline was 56 cells/mm(3) (IQR
      8-138), and 19% had lifetime alcohol problems (CAGE >/= 2). Severe liver enzyme
      elevations (LEEs) of grade 3-4 were rare (2.2%); however, 1 patient died in the
      setting of grade 4 LEEs. Grade 1-4 LEEs occurred among 22.2% of participants, and
      9.8% had new grade 1-4 LEEs after the initiation of treatment. DISCUSSION: The
      authors found that LEEs were common but that severe hepatotoxicity in persons
      initiating NVP-based ART was infrequent yet potentially life-threatening.
      Monitoring for NVP-related severe hepatic toxicity should be part of expanding
      antiretroviral treatment programs in resource-limited settings.

PMID- 17537998
TI  - Prediction of Virologic Outcome of Salvage Antiretroviral Treatment by Different
      Systems for Interpreting Genotypic HIV Drug Resistance.
AB  - The authors assessed the predictive capacity of 3 rule-based algorithms (Bergamo,
      Stanford University, Rega Institute) for HIV genotypic interpretation. A total of
      1132 postgenotypic regimens in 533 patients were considered. The genotypic
      sensitivity score (GSS) was strongly associated (P < .0001) with the virologic
      outcome (1 log HIV-RNA reduction). The 3 algorithms had a highly significant
      prediction efficiency. The Bergamo algorithm receiver-operating characteristic
      curve area under the curve (AUC) for the prediction of >/=1 log HIV-RNA reduction
      was 0.753 (95% confidence interval, 0.725-0.781), testifying that the prediction
      was significantly different (P < .0001) from simple chance. The AUCs obtained by
      the 2 other systems were similar (0.752 Stanford; 0.741 Rega). The predictive
      capacity of the algorithms was not influenced by the type of antiviral drugs
      used. The 3 considered rule-based algorithms for the interpretation of HIV
      genotypic resistance yield congruent results and may effectively predict the
      virologic outcome of rescue therapy. Their use may help clinicians in
      interpreting mutational patterns and in making therapeutic choices.

PMID- 17537999
TI  - The lessons learned from paying antiretroviral therapy in Malawi.

PMID- 17538000
TI  - Use of Dronabinol Improves Appetite and Reverses Weight Loss in HIV/AIDS-Infected
      Patients.
AB  - OBJECTIVE: To determine whether dronabinol affects appetite and weight status in
      patients living with HIV/AIDS. METHODS: A retrospective chart review was
      conducted to analyze weight and appetite changes and nausea status in patients
      with HIV/AIDS who received dronabinol for 3 to 12 months from January 11, 1993,
      to March 17, 2003. RESULTS: Of the 117 patients who lost weight before baseline,
      63% maintained or gained weight. In patients receiving dronabinol for 1 year, the
      mean weight gain (+/- SD) was 3.7 +/- 10.6 lb. The percentage of patients
      experiencing loss of appetite decreased significantly from 71% at baseline to 26%
      at 1 month (P < .001) and continued to decline throughout the trial. The
      percentage of patients experiencing nausea at baseline (38%) decreased
      consistently from week 2 on; this change from baseline was significant at month 6
      (P = .031). CONCLUSION: When taken for 3 months to 1 year, dronabinol
      significantly improves appetite and reverses weight loss in patients living with
      HIV/AIDS.

PMID- 17538001
TI  - Profile of Hospitalized HIV-Infected Persons in the Highly Active Antiretroviral
      Therapy Era in Barbados.
AB  - OBJECTIVES: To investigate the reasons for hospitalization and its outcome in the
      era of highly active antiretroviral therapy (HAART) in Barbados. This report also
      describes the profiles of the HIV-infected persons who were hospitalized in the
      HAART era. METHODS: The authors examined the admission case notes to conduct an
      observational, retrospective study of all HIV-infected patients admitted to the
      Queen Elizabeth Hospital (QEH) during September 1, 2004, through March 31, 2005.
      Data collected included patients' profile, including the date of diagnosis of HIV
      infection. Outcome of the current admission in terms of discharge or death and
      the final diagnosis at the time of discharge or death was noted. RESULTS: Over
      the 6-month period, there were 160 adult admissions to the QEH where HIV/AIDS was
      at least one of the final diagnoses. Eighty-four (52.5%) admissions were in
      persons who were known to be HIV infected prior to the current admission, where a
      diagnosis of HIV infection was made for the first time during the current
      hospitalization in the remaining 76 (47.5%) cases. Nearly two thirds of those
      hospitalized and who had a CD4 count done had CD4 counts of < 200. Overall,
      opportunistic infection was the most common (38.1%), at discharge or as a final
      diagnosis, followed by serious bacterial infections, anemia, and HIV nephropathy.
      The outcome of these admissions was death in 30 (18.7%) cases, whereas the
      patient was discharged in the remaining 130 (81.3%) cases. CONCLUSIONS: A
      significant proportion of the hospitalized HIV-infected persons in the HAART era
      is newly diagnosed. The majority of those hospitalized had severe
      immunodeficiency, and consequently opportunistic infection was the most common
      final diagnosis.

PMID- 17538002
TI  - A program to provide antiretroviral therapy to residents of an urban slum in
      Nairobi, Kenya.
AB  - OBJECTIVE: To evaluate retention in care and response to therapy for patients
      enrolled in an antiretroviral treatment program in a severely resource
      constrained setting. METHODS: We evaluated patients enrolled between February 26,
      2003, and February 28, 2005, in a community clinic in Kibera, an informal
      settlement, in Nairobi, Kenya. Midlevel providers offered simplified,
      standardized antiretroviral therapy (ART) regimens and monitored patients
      clinically and with basic laboratory tests. Clinical, immunologic, and virologic
      indicators were used to assess response to ART; adherence was determined by 3-day
      recall. A total of 283 patients (70% women; median baseline CD4 count, 157 cells/
      mm(3); viral load, 5.16 log copies/mL) initiated ART and were followed for a
      median of 7.1 months (n = 2384 patient-months). RESULTS: At 1 year, the median
      CD4 count change was +124.5 cells/mm(3) (n = 74; interquartile range, 42 to 180),
      and 71 (74%) of 96 patients had viral load <400 copies/mL. The proportion of
      patients reporting 100% adherence over the 3 days before monthly clinic visits
      was 94% to 100%. As of February 28, 2005, a total of 239 patients (84%) remained
      in care, 22 (8%) were lost to follow-up, 12 (4%) were known to have died, 5 (2%)
      had stopped ART, 3 (1%) moved from the area, and 2 (< 1% ) transferred care.
      CONCLUSIONS: Response to ART in this slum population was comparable to that seen
      in industrialized settings. With government commitment, donor support, and
      community involvement, it is feasible to implement successful ART programs in
      extremely challenging social and environmental conditions.

PMID- 17538003
TI  - Results of an Antiretroviral Adherence Intervention: STAR (Staying Healthy:
      Taking Antiretrovirals Regularly).
AB  - A randomized 2-group medication adherence intervention is evaluated with HIV
      infected adults (N = 141) assessed at baseline, 3-, and 9-month follow-ups.
      Cognitive (self-efficacy, behavioral intent), mental health (depression, well
      being), and substance use indicators were the outcome measures. In addition, a
      posttest-only analysis from 3 to 9 months evaluates intervention impact on
      antiretroviral adherence, measured through Medication Event Monitoring System and
      pill counts. Compared to the standard care group, the intervention group showed
      significant increases in adherence self-efficacy and behavioral intent at 3 and 9
      months and marginal improvements in mental health. Although the standard care
      group had higher adherence at 3 months (no baseline data were available prior to
      intervention), intervention group patients showed significant increases in
      adherence from 3 to 9 months. Although adherence levels achieved by intervention
      patients may not be sufficient for virological control, this is one of the first
      studies to provide promising results of longer term effectiveness of a behavioral
      adherence intervention.

PMID- 17538004
TI  - Safety of HIV-1 Perinatal Transmission Prophylaxis With Zidovudine and Nevirapine
      in Rural South India.
AB  - BACKGROUND: The authors assessed acceptance and safety of, and adherence to,
      perinatal HIV-1 transmission prophylaxis at 2 public hospitals in rural Tamil
      Nadu, India. METHODS: Eligible HIV-1-infected women were offered zidovudine (ZDV)
      beginning at 28-weeks gestation until delivery. Their infants received ZDV for 6
      weeks. A subsequent revision to the protocol added 1 dose of nevirapine (NVP) for
      mother and infant. RESULTS: Sixty of 67 women (90%) met inclusion criteria for
      the cohort study. Thirty-four of 36 eligible women and all 19 eligible live born
      infants received prophylaxis on study. Infant, but not maternal, adherence to ZDV
      varied by antiretroviral prophylaxis group (those receiving combined prophylaxis
      with ZDV and NVP had lower median adherence) (P = .02). Neutropenia (usually
      transient) was the most common severe adverse event. Only 1 of 5 women with
      neutropenia possibly related to ZDV permanently discontinued ZDV. ZDV was not
      discontinued for any infant. CONCLUSION: With the exception of neutropenia,
      usually transient and always without clinical consequences, long-term ZDV (with
      or without NVP prophylaxis) is well tolerated.

PMID- 17538005
TI  - Modulation of ADP-induced platelet activation by aspirin and pravastatin: role of
      lectin-like oxidized low-density lipoprotein receptor-1, nitric oxide, oxidative
      stress, and inside-out integrin signaling.
AB  - Lectin-like oxidized low-density lipoprotein (LDL) receptor-1 (LOX-1), a receptor
      for oxidized-LDL, is up-regulated in activated endothelial cells, and it plays a
      role in atherothrombosis. However, its role in platelet aggregation is unclear.
      Both aspirin and HMG CoA reductase inhibitors (statins) reduce LOX-1 expression
      in endothelial cells. In this study, we investigated the effect of aspirin and
      pravastatin on LOX-1 expression on plate-lets. After ADP stimulation, mean
      fluorescence intensity of LOX-1 expression on platelets increased 1.5- to 2.0
      fold. Blocking LOX-1 inhibited ADP-induced platelet aggregation in a
      concentration- and time-dependent manner. We also established that LOX-1 is
      important for ADP-stimulated inside-out activation of platelet alpha(IIb)beta(3)
      and alpha(2)beta(1) integrins (fibrinogen receptors). The specificity of this
      interaction was determined by arginine-glycine-aspartate-peptide inhibition.
      Furthermore, we found that LOX-1 inhibition of integrin activation is mediated by
      inhibition of protein kinase C activity. In other experiments, treatment with
      aspirin (1-10 mM) and pravastatin (1-5 microM) reduced platelet LOX-1 expression,
      with a synergistic effect of the combination of aspirin and pravastatin. Aspirin
      and pravastatin both reduced reactive oxygen species (ROS) released by activated
      platelets measured as malonyldialdehyde (MDA) release and nitrate/nitrite ratio.
      Aspirin and pravastatin also enhanced nitric oxide (NO) release measured as
      nitrite/nitrite + nitrate (NOx) ratio in platelet supernates. Small
      concentrations of aspirin and pravastatin had a synergistic effect on the
      inhibition of MDA release and enhancement of nitrite/NOx. Thus, LOX-1 is
      important for ADP-mediated platelet integrin activation, possibly through protein
      kinase C activation. Furthermore, aspirin and pravastatin inhibit LOX-1
      expression on platelets in part by favorably affecting ROS and NO release from
      activated platelets.

PMID- 17538006
TI  - Structurally unique inhibitors of human mitogen-activated protein kinase
      phosphatase-1 identified in a pyrrole carboxamide library.
AB  - Mitogen-activated protein kinase phosphatase 1 (MKP-1) is a tyrosine phosphatase
      superfamily member that dephosphorylates and inactivates cardinal mitogen
      activated protein kinase (MAPK) substrates, such as p38, c-Jun NH(2)-terminal
      kinase, and extracellular signal-regulated kinase. Although these MAPK substrates
      regulate many essential cellular processes associated with human diseases, few
      pharmacological inhibitors have been described. The lack of readily available
      selective MKP-1 inhibitors has severely limited interrogation of its biological
      role and was one rationale for using a recently described tricyclic pyrrole-2
      carboxamide library in our screening efforts. In this report we demonstrate the
      pharmacological richness of the pyrrole carboxamide library by the finding that
      10 of 172 members inhibited human MKP-1. Two of the pyrrole carboxamides, PSI2106
      and MDF2085, were especially notable in vitro inhibitors of recombinant human MKP
      1 enzyme activity with IC(50) values of 8.0 +/- 0.9 and 8.3 +/- 0.8 microM,
      respectively. Both showed some selectivity for MKP-1 over the closely related
      phosphatases MKP-3, Cdc25B, VHR, and PTP1B. Computational examination of the
      surface properties near the catalytic site revealed that the phosphatases studied
      differ significantly in their electrostatic potential at the substrate binding
      site. The compounds inhibited MKP-1 reversibly but displayed mixed kinetics.
      Phosphatase inhibition was retained in the presence of physiologically relevant
      concentrations of glutathione. Molecular docking studies suggested that PSI2106
      may interact with His(229) and Phe(299) on MKP-1. These results reveal the power
      of using a small focused library for identifying pharmacological probes.

PMID- 17538007
TI  - Human neural precursor cells express functional kappa-opioid receptors.
AB  - Neural stem cells (NSCs) play an important role in the developing as well as
      adult brain. NSCs have been shown to migrate toward sites of injury in the brain
      and to participate in the process of brain repair. Like NSCs, cultured human
      neural precursor cells (NPCs) are self-renewing, multipotent cells capable of
      differentiating into neurons, astrocytes, and oligodendrocytes and of migrating
      toward chemotactic stimuli. Cellular and environmental factors are important for
      NPC proliferation and migration. Expression of kappa-opioid receptors (KORs) and
      mu-opioid receptors (MORs) in murine embryonic stem cells and of MORs and delta
      opioid receptors in rodent neuronal precursors, as well as hippocampal
      progenitors has been reported by other investigators. In this study, we
      demonstrated robust expression of KORs in highly enriched (>90% nestin-positive)
      human fetal brain-derived NPCs. We found that KOR ligands, dynorphin(1-17) and
      trans-3,4-dichloro-N-methyl-N[2-(1-pyrolidinyl)cyclohexyl] benzeneacetamide
      methanesulfonate (U50,488) but not dynorphin(2-17), stimulated proliferation and
      migration of NPCs in a concentration-dependent manner. NPC proliferation was
      maximally stimulated at 10(-14) M dynorphin(1-17) and 10(-12) M U50,488. The KOR
      selective antagonist, nor-binaltorphimine, partially blocked the migratory and
      proliferative effects of KOR agonists supporting, at least in part, the
      involvement of a KOR-related mechanism. As has been described for rodent P19
      embryonal carcinoma stem cells, retinoic acid treatment markedly suppressed KOR
      mRNA expression in human NPCs. Taken together, the results of this study suggest
      that activation of KORs alters functional properties of NPCs/NSCs that are
      relevant to human brain development and repair.

PMID- 17538008
TI  - Blockade of AT1 receptor reduces apoptosis, inflammation, and oxidative stress in
      normotensive rats with intracerebral hemorrhage.
AB  - Angiotensin II exerts its central nervous system effects primarily via its
      receptors AT1 and AT2, and it participates in the pathogenesis of ischemia via
      AT1. The selective AT1 receptor blocker (ARB) is used in the hypertension
      treatment, and it exerts a variety of pleiotropic effects, including
      antioxidative, antiapoptotic, and anti-inflammatory effects. In this study, we
      investigated the therapeutic effect of the ARB telmisartan in experimental
      intracerebral hemorrhage (ICH) in normotensive rats. ICH was induced via the
      collagenase infusion or autologous blood injection. Either telmisartan at 30
      mg/kg/dose or phosphate-buffered saline was orally administered 2 h after ICH
      induction. We evaluated hemorrhage volume, brain water content, and functional
      recovery, and we performed the histological analysis for terminal
      deoxynucleotidyl transferase dUTP nick-end labeling, leukocyte infiltration, and
      microglia activation. A variety of intracellular signals, in terms of oxidative
      stress, apoptotic molecules, and inflammatory mediators, were also measured.
      Telmisartan reduced hemorrhage volume, brain edema, and inflammatory or apoptotic
      cells in the perihematomal area. Telmisartan was noted to induce the expression
      of endothelial nitric-oxide synthase and peroxisome proliferator-activated
      receptor gamma and decrease oxidative stress, apoptotic signal, tumor necrosis
      factor-alpha, and cyclooxygenase-2 expression. The telmisartan-treated rats
      exhibited less pronounced neurological deficits and recovered better. Thus,
      telmisartan seems to offer neural protection, including antiapoptosis, anti
      inflammatory, and antioxidant benefits in the intracerebral hemorrhage rat model.

PMID- 17538010
TI  - Rectum dose analysis employing a multi-purpose brachytherapy phantom.
AB  - PURPOSE: It is difficult to reproduce a brachytherapy measurement because of
      changes in the rectal shape during inter-fraction. We constructed a multi-purpose
      brachytherapy phantom (MPBP) and reproduced the same conditions found in actual
      therapy. We further attempted to apply the measured optimal dose to reduce rectal
      complications. METHODS: A measured dose was administered at rectal reference
      point R1 using a diode detector in four patients who used a tandem and ovoid in
      brachytherapy for carcinoma of the cervix. A total number of 20 rectal dose
      measurements were performed five times per patient. In addition, discrepancies in
      the set-up of the diode detector were analyzed with each repetitive measurement.
      After reproducing the same conditions as found in actual therapy using a multi
      function applicator (MFA) in the multi-purpose brachytherapy phantom constructed
      for this study, the dose was measured at reference points in the rectum using a
      thermoluminescence dosimeter (TLD). RESULTS: According to the discrepancies
      measured in the set-up using a diode detector, Patient 1 showed a maximum value
      of 11.25 +/- 0.95 mm in the Y direction, Patients 2 and 3 exhibited 9.90 +/- 2.40
      mm and 20.85 +/- 4.50 mm in the Z direction, respectively. Patient 4 showed 19.15
      +/- 3.33 mm in the Z direction. In addition, values of the mean dose according to
      the position of the diode detector were recorded as 122.82 +/- 7.96-323.78 +/-
      11.16 cGy. In the measured results for TLD in an MPBP, relative error for
      Patients 1 and 4 at the rectal reference point R2 were a maximum of 8.6 and 7.7%,
      respectively. For Patients 2 and 3 they were 1.7 and 1.2%, respectively.
      Furthermore, the dose measured at point R1 and R2 exhibited values approximately
      1.7-8.6% higher than the dose calculated in advance, excluding point R1 in
      Patient 2. The discrepancies in the set-up owing to repetitive measurements and
      alterations in dosage according to these changes were not analyzed. It was
      evident that the relative error between the calculated and measured value was
      within 15%, which was allowable according to the recommendations by the American
      Association of Physicists in Medicine (AAPM). CONCLUSIONS: The multi-purpose
      brachytherapy phantom constructed for this study successfully reproduced an
      optimal dose measured under the same conditions found in actual therapy in which
      the dose was precisely analyzed at a rectal reference point. In addition, these
      results were considered reliable and applicable for dose optimization before
      applying therapy using the measured data from the phantom in order to reduce
      rectal complications.

PMID- 17538011
TI  - MRX-dependent DNA damage response to short telomeres.
AB  - Telomere structure allows cells to distinguish the natural chromosome ends from
      double-strand breaks (DSBs). However, DNA damage response proteins are intimately
      involved in telomere metabolism, suggesting that functional telomeres may be
      recognized as DNA damage during a time window. Here we show by two different
      systems that short telomeres are recognized as DSBs during the time of their
      replication, because they induce a transient MRX-dependent DNA damage checkpoint
      response during their prolonged elongation. The MRX complex, which is recruited
      at telomeres under these conditions, dissociates from telomeres concomitantly
      with checkpoint switch off when telomeres reach a new equilibrium length. We also
      show that MRX recruitment to telomeres is sufficient to activate the checkpoint
      independently of telomere elongation. We propose that MRX can signal checkpoint
      activation by binding to short telomeres only when they become competent for
      elongation. Because full-length telomeres are refractory to MRX binding and the
      shortest telomeres are elongated of only a few base pairs per generation, this
      limitation may prevent unscheduled checkpoint activation during an unperturbed S
      phase.

PMID- 17538012
TI  - The M-Ras-RA-GEF-2-Rap1 pathway mediates tumor necrosis factor-alpha dependent
      regulation of integrin activation in splenocytes.
AB  - The Rap1 small GTPase has been implicated in regulation of integrin-mediated
      leukocyte adhesion downstream of various chemokines and cytokines in many aspects
      of inflammatory and immune responses. However, the mechanism for Rap1 regulation
      in the adhesion signaling remains unclear. RA-GEF-2 is a member of the multiple
      member family of guanine nucleotide exchange factors (GEFs) for Rap1 and
      characterized by the possession of a Ras/Rap1-associating domain, interacting
      with M-Ras-GTP as an effector, in addition to the GEF catalytic domain. Here, we
      show that RA-GEF-2 is specifically responsible for the activation of Rap1 that
      mediates tumor necrosis factor-alpha (TNF-alpha)-triggered integrin activation.
      In BAF3 hematopoietic cells, activated M-Ras potently induced lymphocyte function
      associated antigen 1 (LFA-1)-mediated cell aggregation. This activation was
      totally abrogated by knockdown of RA-GEF-2 or Rap1. TNF-alpha treatment activated
      LFA-1 in a manner dependent on M-Ras, RA-GEF-2, and Rap1 and induced activation
      of M-Ras and Rap1 in the plasma membrane, which was accompanied by recruitment of
      RA-GEF-2. Finally, we demonstrated that M-Ras and RA-GEF-2 were indeed involved
      in TNF-alpha-stimulated and Rap1-mediated LFA-1 activation in splenocytes by
      using mice deficient in RA-GEF-2. These findings proved a crucial role of the
      cross-talk between two Ras-family GTPases M-Ras and Rap1, mediated by RA-GEF-2,
      in adhesion signaling.

PMID- 17538013
TI  - Nucleoporins prevent DNA damage accumulation by modulating Ulp1-dependent
      sumoylation processes.
AB  - Increasing evidences suggest that nuclear pore complexes (NPCs) control different
      aspects of nuclear metabolism, including transcription, nuclear organization, and
      DNA repair. We previously established that the Nup84 complex, a major NPC
      building block, is part of a genetic network involved in DNA repair. Here, we
      show that double-strand break (DSB) appearance is linked to a shared function of
      the Nup84 and the Nup60/Mlp1-2 complexes. Mutants within these complexes exhibit
      similar genetic interactions and alteration in DNA repair processes as mutants of
      the SUMO-protease Ulp1. Consistently, these nucleoporins are required for
      maintenance of proper Ulp1 levels at NPCs and for the establishment of the
      appropriate sumoylation of several cellular proteins, including the DNA repair
      factor Yku70. Moreover, restoration of nuclear envelope-associated Ulp1 in
      nucleoporin mutants reestablishes proper sumoylation patterns and suppresses DSB
      accumulation and genetic interactions with DNA repair genes. Our results thus
      provide a molecular mechanism that underlies the connection between NPC and
      genome stability.

PMID- 17538014
TI  - The kinesin-13 proteins Kif2a, Kif2b, and Kif2c/MCAK have distinct roles during
      mitosis in human cells.
AB  - The human genome has three unique genes coding for kinesin-13 proteins called
      Kif2a, Kif2b, and MCAK (Kif2c). Kif2a and MCAK have documented roles in mitosis,
      but the function of Kif2b has not been defined. Here, we show that Kif2b is
      expressed at very low levels in cultured cells and that GFP-Kif2b localizes
      predominately to centrosomes and midbodies, but also to spindle microtubules and
      transiently to kinetochores. Kif2b-deficient cells assemble monopolar or
      disorganized spindles. Chromosomes in Kif2b-deficient cells show typical
      kinetochore-microtubule attachments, but the velocity of movement is reduced
      approximately 80% compared with control cells. Some Kif2b-deficient cells attempt
      anaphase, but the cleavage furrow regresses and cytokinesis fails. Like Kif2a
      deficient cells, bipolar spindle assembly can be restored to Kif2b-deficient
      cells by simultaneous deficiency of MCAK or Nuf2 or treatment with low doses of
      nocodazole. However, Kif2b-deficient cells are unique in that they assemble
      bipolar spindles when the pole focusing activities of NuMA and HSET are
      perturbed. These data demonstrate that Kif2b function is required for spindle
      assembly and chromosome movement and that the microtubule depolymerase activities
      of Kif2a, Kif2b, and MCAK fulfill distinct functions during mitosis in human
      cells.

PMID- 17538015
TI  - Acetylcholinesterase mobility and stability at the neuromuscular junction of
      living mice.
AB  - Acetylcholinesterase (AChE) is an enzyme that terminates acetylcholine
      neurotransmitter function at the synaptic cleft of cholinergic synapses. However,
      the mechanism by which AChE number and density are maintained at the synaptic
      cleft is poorly understood. In this work, we used fluorescence recovery after
      photobleaching, photo-unbinding, and quantitative fluorescence imaging to
      investigate the surface mobility and stability of AChE at the adult innervated
      neuromuscular junction of living mice. In wild-type synapses, we found that
      nonsynaptic (perisynaptic and extrasynaptic) AChEs are mobile and gradually
      recruited into synaptic sites and that most of the trapped AChEs come from the
      perijunctional pool. Selective labeling of a subset of synaptic AChEs within the
      synapse by using sequential unbinding and relabeling with different colors of
      streptavidin followed by time-lapse imaging showed that synaptic AChEs are nearly
      immobile. At neuromuscular junctions of mice deficient in alpha-dystrobrevin, a
      component of the dystrophin glycoprotein complex, we found that the density and
      distribution of synaptic AChEs are profoundly altered and that the loss rate of
      AChE significantly increased. These results demonstrate that nonsynaptic AChEs
      are mobile, whereas synaptic AChEs are more stable, and that alpha-dystrobrevin
      is important for controlling the density and stability of AChEs at neuromuscular
      synapses.

PMID- 17538016
TI  - Immobilization of the type XIV myosin complex in Toxoplasma gondii.
AB  - The substrate-dependent movement of apicomplexan parasites such as Toxoplasma
      gondii and Plasmodium sp. is driven by the interaction of a type XIV myosin with
      F-actin. A complex containing the myosin-A heavy chain, a myosin light chain, and
      the accessory protein GAP45 is attached to the membranes of the inner membrane
      complex (IMC) through its tight interaction with the integral membrane
      glycoprotein GAP50. For the interaction of this complex with F-actin to result in
      net parasite movement, it is necessary that the myosin be immobilized with
      respect to the parasite and the actin with respect to the substrate the parasite
      is moving on. We report here that the myosin motor complex of Toxoplasma is
      firmly immobilized in the plane of the IMC. This does not seem to be accomplished
      by direct interactions with cytoskeletal elements. Immobilization of the motor
      complex, however, does seem to require cholesterol. Both the motor complex and
      the cholesterol are found in detergent-resistant membrane domains that encompass
      a large fraction of the inner membrane complex surface. The observation that the
      myosin XIV motor complex of Toxoplasma is immobilized within this cholesterol
      rich membrane likely extends to closely related pathogens such as Plasmodium and
      possibly to other eukaryotes.

PMID- 17538017
TI  - Plasma membrane and nuclear localization of G protein coupled receptor kinase 6A.
AB  - G protein-coupled receptor (GPCR) kinases (GRKs) specifically phosphorylate
      agonist-occupied GPCRs at the inner surface of the plasma membrane (PM), leading
      to receptor desensitization. Here we show that the C-terminal 30 amino acids of
      GRK6A contain multiple elements that either promote or inhibit PM localization.
      Disruption of palmitoylation by individual mutation of cysteine 561, 562, or 565
      or treatment of cells with 2-bromopalmitate shifts GRK6A from the PM to both the
      cytoplasm and nucleus. Likewise, disruption of the hydrophobic nature of a
      predicted amphipathic helix by mutation of two leucines to alanines at positions
      551 and 552 causes a loss of PM localization. Moreover, acidic amino acids in the
      C-terminus appear to negatively regulate PM localization; mutational replacement
      of several acidic residues with neutral or basic residues rescues PM localization
      of a palmitoylation-defective GRK6A. Last, we characterize the novel nuclear
      localization, showing that nuclear export of nonpalmitoylated GRK6A is sensitive
      to leptomycin B and that GRK6A contains a potential nuclear localization signal.
      Our results suggest that the C-terminus of GRK6A contains a novel electrostatic
      palmitoyl switch in which acidic residues weaken the membrane-binding strength of
      the amphipathic helix, thus allowing changes in palmitoylation to regulate PM
      versus cytoplasmic/nuclear localization.

PMID- 17538018
TI  - Canonical interaction of cyclin G associated kinase with adaptor protein 1
      regulates lysosomal enzyme sorting.
AB  - The adaptor protein 1 (AP1) complex is a heterotetramer that participates in
      cargo sorting into clathrin-coated vesicles at the trans-Golgi network (TGN) and
      endosomes. The gamma subunit of AP1 possesses a C-terminal "ear" domain that
      recruits a cohort of accessory proteins through recognition of a shared canonical
      motif, PsiG[PDE][PsiLM] (where Psi is an aromatic residue). The physiological
      relevance of these ear-motif interactions, however, remains to be demonstrated.
      Here we report that the cyclin G-associated kinase (GAK) has two sequences
      fitting this motif, FGPL and FGEF, which mediate binding to the AP1-gamma-ear
      domain in vitro. Mutation of both gamma-ear-binding sequences or depletion of AP1
      gamma by RNA interference (RNAi) decreases the association of GAK with the TGN in
      vivo. Depletion of GAK by RNAi impairs the sorting of the acid hydrolase,
      cathepsin D, to lysosomes. Importantly, expression of RNAi-resistant GAK restores
      the lysosomal sorting of cathepsin D in cells depleted of endogenous GAK, whereas
      expression of a similar construct bearing mutations in both gamma-ear-binding
      sequences fails to correct the sorting defect. Thus, interactions between the
      PsiG[PDE][PsiLM]-motif sequences in GAK and the AP1-gamma-ear domain are critical
      for the recruitment of GAK to the TGN and the function of GAK in lysosomal enzyme
      sorting.

PMID- 17538019
TI  - Phosphatidylinositol-4,5 bisphosphate produced by PIP5KIgamma regulates gelsolin,
      actin assembly, and adhesion strength of N-cadherin junctions.
AB  - Phosphoinositides regulate several actin-binding proteins but their role at
      intercellular adhesions has not been defined. We found that phosphatidylinositol
      4,5-bisphosphate (PI(4,5)P2) was generated at sites of N-cadherin-mediated
      intercellular adhesion and was a critical regulator of intercellular adhesion
      strength. Immunostaining for PI(4,5)P2 or transfection with GFP-PH-PLCdelta
      showed that PI(4,5)P2 was enriched at sites of N-cadherin adhesions and this
      enrichment required activated Rac1. Isoform-specific immunostaining for type I
      phosphatidylinositol 4-phosphate 5 kinase (PIP5KI) showed that PIP5KIgamma was
      spatially associated with N-cadherin-Fc beads. Association of PIP5KIgamma with N
      cadherin adhesions was in part dependent on the activation of RhoA. Transfection
      with catalytically inactive PIP5KIgamma blocked the enrichment of PI(4,5)P2
      around beads. Catalytically inactive PIP5KIgamma or a cell-permeant peptide that
      mimics and competes for the PI(4,5)P2-binding region of the actin-binding protein
      gelsolin inhibited incorporation of actin monomers in response to N-cadherin
      ligation and reduced intercellular adhesion strength by more than twofold.
      Gelsolin null fibroblasts transfected with a gelsolin severing mutant containing
      an intact PI(4,5)P2 binding region, demonstrated intercellular adhesion strength
      similar to wild-type transfected controls. We conclude that PIP5KIgamma-mediated
      generation of PI(4,5)P2 at sites of N-cadherin contacts regulates intercellular
      adhesion strength, an effect due in part to PI(4,5)P2-mediated regulation of
      gelsolin.

PMID- 17538020
TI  - The clathrin adaptor complex AP-1 binds HIV-1 and MLV Gag and facilitates their
      budding.
AB  - Retroviral assembly is driven by Gag, and nascent viral particles escape cells by
      recruiting the machinery that forms intralumenal vesicles of multivesicular
      bodies. In this study, we show that the clathrin adaptor complex AP-1 is involved
      in retroviral release. The absence of AP-1mu obtained by genetic knock-out or by
      RNA interference reduces budding of murine leukemia virus (MLV) and HIV-1,
      leading to a delay of viral propagation in cell culture. In contrast,
      overexpression of AP-1mu enhances release of HIV-1 Gag. We show that the AP-1
      complex facilitates retroviral budding through a direct interaction between the
      matrix and AP-1mu. Less MLV Gag is found associated with late endosomes in cells
      lacking AP-1, and our results suggest that AP-1 and AP-3 could function on the
      same pathway that leads to Gag release. In addition, we find that AP-1 interacts
      with Tsg101 and Nedd4.1, two cellular proteins known to be involved in HIV-1 and
      MLV budding. We propose that AP-1 promotes Gag release by transporting it to
      intracellular sites of active budding, and/or by facilitating its interactions
      with other cellular partners.

PMID- 17538021
TI  - Fast turnover of L1 adhesions in neuronal growth cones involving both surface
      diffusion and exo/endocytosis of L1 molecules.
AB  - We investigated the interplay between surface trafficking and binding dynamics of
      the immunoglobulin cell adhesion molecule L1 at neuronal growth cones. Primary
      neurons were transfected with L1 constructs bearing thrombin-cleavable green
      fluorescent protein (GFP), allowing visualization of newly exocytosed L1 or
      labeling of membrane L1 molecules by Quantum dots. Intracellular L1-GFP vesicles
      showed preferential centrifugal motion, whereas surface L1-GFP diffused randomly,
      revealing two pathways to address L1 to adhesive sites. We triggered L1 adhesions
      using microspheres coated with L1-Fc protein or anti-L1 antibodies, manipulated
      by optical tweezers. Microspheres coupled to the actin retrograde flow at the
      growth cone periphery while recruiting L1-GFP molecules, of which 50% relied on
      exocytosis. Fluorescence recovery after photobleaching experiments revealed a
      rapid recycling of L1-GFP molecules at L1-Fc (but not anti-L1) bead contacts,
      attributed to a high lability of L1-L1 bonds at equilibrium. L1-GFP molecules
      truncated in the intracellular tail as well as neuronal cell adhesion molecules
      (NrCAMs) missing the clathrin adaptor binding sequence showed both little
      internalization and reduced turnover rates, indicating a role of endocytosis in
      the recycling of mature L1 contacts at the base of the growth cone. Thus, unlike
      for other molecules such as NrCAM or N-cadherin, diffusion/trapping and
      exo/endocytosis events cooperate to allow the fast renewal of L1 adhesions.

PMID- 17538022
TI  - Mechanism underlying the iron-dependent nuclear export of the iron-responsive
      transcription factor Aft1p in Saccharomyces cerevisiae.
AB  - Aft1p is an iron-responsive transcriptional activator that plays a central role
      in maintaining iron homeostasis in Saccharomyces cerevisiae. Aft1p is regulated
      primarily by iron-induced shuttling of the protein between the nucleus and
      cytoplasm, but its nuclear import is not regulated by iron. Here, we have shown
      that the nuclear export of Aft1p is promoted in the presence of iron and that
      Msn5p is the nuclear export receptor (exportin) for Aft1p. Msn5p recognizes Aft1p
      in the iron-replete condition. Phosphorylation of S210 and S224 in Aft1p, which
      is not iron dependent, and the iron-induced intermolecular interaction of Aft1p
      are both essential for its recognition by Msn5p. Mutation of Cys291 of Aft1p to
      Phe, which causes Aft1p to be retained in the nucleus and results in constitutive
      activation of Aft1-target genes, disrupts the intermolecular interaction of
      Aft1p. Collectively, these results suggest that iron induces a conformational
      change in Aft1p, in which Aft1p Cys291 plays a critical role, and that, in turn,
      Aft1p is recognized by Msn5p and exported into the cytoplasm in an iron-dependent
      manner.

PMID- 17538023
TI  - Identification of Arabidopsis cyclase-associated protein 1 as the first
      nucleotide exchange factor for plant actin.
AB  - The actin cytoskeleton powers organelle movements, orchestrates responses to
      abiotic stresses, and generates an amazing array of cell shapes. Underpinning
      these diverse functions of the actin cytoskeleton are several dozen accessory
      proteins that coordinate actin filament dynamics and construct higher-order
      assemblies. Many actin-binding proteins from the plant kingdom have been
      characterized and their function is often surprisingly distinct from mammalian
      and fungal counterparts. The adenylyl cyclase-associated protein (CAP) has
      recently been shown to be an important regulator of actin dynamics in vivo and in
      vitro. The disruption of actin organization in cap mutant plants indicates
      defects in actin dynamics or the regulated assembly and disassembly of actin
      subunits into filaments. Current models for actin dynamics maintain that actin
      depolymerizing factor (ADF)/cofilin removes ADP-actin subunits from filament ends
      and that profilin recharges these monomers with ATP by enhancing nucleotide
      exchange and delivery of subunits onto filament barbed ends. Plant profilins,
      however, lack the essential ability to stimulate nucleotide exchange on actin,
      suggesting that there might be a missing link yet to be discovered from plants.
      Here, we show that Arabidopsis thaliana CAP1 (AtCAP1) is an abundant cytoplasmic
      protein; it is present at a 1:3 M ratio with total actin in suspension cells.
      AtCAP1 has equivalent affinities for ADP- and ATP-monomeric actin (Kd
      approximately 1.3 microM). Binding of AtCAP1 to ATP-actin monomers inhibits
      polymerization, consistent with AtCAP1 being an actin sequestering protein.
      However, we demonstrate that AtCAP1 is the first plant protein to increase the
      rate of nucleotide exchange on actin. Even in the presence of ADF/cofilin, AtCAP1
      can recharge actin monomers and presumably provide a polymerizable pool of
      subunits to profilin for addition onto filament ends. In turnover assays, plant
      profilin, ADF, and CAP act cooperatively to promote flux of subunits through
      actin filament barbed ends. Collectively, these results and our understanding of
      other actin-binding proteins implicate CAP1 as a central player in regulating the
      pool of unpolymerized ATP-actin.

PMID- 17538024
TI  - Activated ezrin promotes cell migration through recruitment of the GEF Dbl to
      lipid rafts and preferential downstream activation of Cdc42.
AB  - Establishment of polarized cell morphology is a critical factor for migration and
      requires precise spatial and temporal activation of the Rho GTPases. Here, we
      describe a novel role of the actin-binding ezrin/radixin/moesin (ERM)-protein
      ezrin to be involved in recruiting Cdc42, but not Rac1, to lipid raft
      microdomains, as well as the subsequent activation of this Rho GTPase and the
      downstream effector p21-activated kinase (PAK)1, as shown by fluorescence
      lifetime imaging microscopy. The establishment of a leading plasma membrane and
      the polarized morphology necessary for random migration are also dependent on ERM
      function and Cdc42 in motile breast carcinoma cells. Mechanistically, we show
      that the recruitment of the ERM-interacting Rho/Cdc42-specific guanine nucleotide
      exchange factor Dbl to the plasma membrane and to lipid raft microdomains
      requires the phosphorylated, active conformer of ezrin, which serves to tether
      the plasma membrane or its subdomains to the cytoskeleton. Together these data
      suggest a mechanism whereby precise spatial guanine nucleotide exchange of Cdc42
      by Dbl is dependent on functional ERM proteins and is important for directional
      cell migration.

PMID- 17538025
TI  - Evidence that mono-ADP-ribosylation of CtBP1/BARS regulates lipid storage.
AB  - Mono-ADP-ribosylation is emerging as an important posttranslational modification
      that modulates a variety of cell signaling pathways. Here, we present evidence
      that mono-ADP-ribosylation of the transcriptional corepressor C terminal binding
      protein, brefeldin A (BFA)-induced ADP-ribosylated substrate (CtBP1/BARS)
      regulates neutral lipid storage in droplets that are surrounded by a monolayer of
      phospholipid and associated proteins. CtBP1/BARS is an NAD-binding protein that
      becomes ribosylated when cells are exposed to BFA. Both endogenous lipid droplets
      and droplets enlarged by oleate treatment are lost after 12-h exposure to BFA.
      Lipid loss requires new protein synthesis, and it is blocked by multiple
      ribosylation inhibitors, but it is not stimulated by disruption of the Golgi
      apparatus or the endoplasmic reticulum unfolded protein response. Small
      interfering RNA knockdown of CtBP1/BARS mimics the effect of BFA, and mouse
      embryonic fibroblasts derived from embryos that are deficient in CtBP1/BARS seem
      to be defective in lipid accumulation. We conclude that mono-ADP-ribosylation of
      CtBP1/BARS inactivates its repressor function, which leads to the activation of
      genes that regulate neutral lipid storage.

PMID- 17538026
TI  - The nucleolar Net1/Cfi1-related protein Dnt1 antagonizes the septation initiation
      network in fission yeast.
AB  - The septation initiation network (SIN) and mitotic exit network (MEN) signaling
      pathways regulate cytokinesis and mitotic exit in the yeasts Schizosaccharomyces
      pombe, and Saccharomyces cerevisiae, respectively. One function of these pathways
      is to keep the Cdc14-family phosphatase, called Clp1 in S. pombe, from being
      sequestered and inhibited in the nucleolus. In S. pombe, the SIN and Clp1 act as
      part of a cytokinesis checkpoint that allows cells to cope with cytokinesis
      defects. The SIN promotes checkpoint function by 1) keeping Clp1 out of the
      nucleolus, 2) maintaining the cytokinetic apparatus, and 3) halting the cell
      cycle until cytokinesis is completed. In a screen for suppressors of the SIN
      mutant cytokinesis checkpoint defect, we identified a novel nucleolar protein
      called Dnt1 and other nucleolar proteins, including Rrn5 and Nuc1, which are
      known to be required for rDNA transcription. Dnt1 shows sequence homology to
      Net1/Cfi1, which encodes the nucleolar inhibitor of Cdc14 in budding yeast. Like
      Net1/Cfi1, Dnt1 is required for rDNA silencing and minichromosome maintenance,
      and both Dnt1 and Net1/Cfi1 negatively regulate the homologous SIN and MEN
      pathways. Unlike Net1/Cfi1, which regulates the MEN through the Cdc14
      phosphatase, Dnt1 can inhibit SIN signaling independently of Clp1, suggesting a
      novel connection between the nucleolus and the SIN pathway.

PMID- 17538027
TI  - Rab11A controls the biogenesis of Birbeck granules by regulating Langerin
      recycling and stability.
AB  - The extent to which Rab GTPases, Rab-interacting proteins, and cargo molecules
      cooperate in the dynamic organization of membrane architecture remains to be
      clarified. Langerin, a recycling protein accumulating in the Rab11-positive
      compartments of Langerhans cells, induces the formation of Birbeck granules
      (BGs), which are membrane subdomains of the endosomal recycling network. We
      investigated the role of Rab11A and two members of the Rab11 family of
      interacting proteins, Rip11 and RCP, in Langerin traffic and the biogenesis of
      BGs. The overexpression of a dominant-negative Rab11A mutant or Rab11A depletion
      strongly influenced Langerin traffic and stability and the formation of BGs,
      whereas modulation of other Rab proteins involved in dynamic regulation of the
      endocytic-recycling pathway had no effect. Impairment of Rab11A function led to a
      missorting of Langerin to lysosomal compartments, but inhibition of Langerin
      degradation by chloroquine did not restore the formation of BGs. Loss of RCP, but
      not of Rip11, also had a modest, but reproducible effect on Langerin stability
      and BG biogenesis, pointing to a role for Rab11A-RCP complexes in these events.
      Our results show that Rab11A and Langerin are required for BG biogenesis, and
      they illustrate the role played by a Rab GTPase in the formation of a specialized
      subcompartment within the endocytic-recycling system.

PMID- 17538028
TI  - Evo/devo and the lungfish: the last gasp of intelligent design.

PMID- 17538029
TI  - Crosslinks in blood: transglutaminase and beyond.

PMID- 17538030
TI  - Interaction between HIV gp41 fusion peptide and T cell receptor: putting the
      puzzle pieces back together.

PMID- 17538032
TI  - Congenital neuromuscular disease with uniform type 1 fiber and RYR1 mutation.
AB  - BACKGROUND: Congenital neuromuscular disease with uniform type 1 fiber (CNMDU1)
      is a rare form of congenital myopathy, which is pathologically diagnosed by the
      presence of more than 99% of type 1 fiber, with no specific structural changes.
      Its pathogenic mechanism is still unknown. We recently reported that almost all
      patients with central core disease (CCD) with ryanodine receptor 1 gene (RYR1)
      mutations in the C-terminal domain had type 1 fibers, nearly exclusively, in
      addition to typical central cores. OBJECTIVE: To investigate whether CNMDU1 is
      associated with RYR1 mutation. METHODS: We studied 10 unrelated Japanese patients
      who were diagnosed to have CNMDU1 based on clinical features and muscle pathology
      showing more than 99% type 1 muscle fibers. We extracted genomic DNA from frozen
      muscles and directly sequenced all 106 exons and their flanking intron-exon
      boundaries of RYR1. RESULTS: Four of 10 patients had a heterozygous mutation,
      three missense and one deletion, all in the C-terminal domain of RYR1. Two
      missense mutations were previously reported in CCD patients. Clinically, patients
      with mutations in RYR1 showed milder phenotype compared with those without
      mutations. CONCLUSION: Congenital neuromuscular disease with uniform type 1 fiber
      (CNMDU1) in 40% of patients is associated with mutations in the C-terminal domain
      of RYR1, suggesting that CNMDU1 is allelic to central core disease at least in
      some patients.

PMID- 17538033
TI  - Significant association between leukoaraiosis and metabolic syndrome in healthy
      subjects.
AB  - OBJECTIVE: To investigate the relationship between leukoaraiosis (LA), which has
      been considered as an intermediate substitute of ischemic brain damages, and
      metabolic syndrome (MetS), which attracts attention as a risk factor for
      cerebrovascular diseases, in healthy subjects derived from various age groups.
      METHODS: We studied 1,030 healthy persons at ages between 28 and 78 years (mean,
      52.7 years) with no history of stroke who visited a health care facility for
      routine health checkups. MetS was defined using the criteria of the National
      Cholesterol Education Program Adult Treatment Panel III. LA was assessed using
      the rating scale of the Atherosclerosis Risk in Communities study on MRI.
      Logistic regression analysis was performed to examine associations between LA and
      MetS. RESULTS: A total of 296 (28.8%) subjects had LA on MRI. MetS was
      significantly associated with the presence of LA (adjusted OR, 3.33; 95% CI,
      2.30, 4.84). The association was constant across grades of LA; the adjusted OR
      was 3.41 (95% CI, 2.30, 5.06) for minimal LA and 3.07 (95% CI, 1.75, 5.38) for LA
      combining mild, moderate, and severe grades. As for MetS components, elevated
      blood pressure (adjusted OR, 2.16; 95% CI, 1.57, 2.99), impaired fasting glucose
      (adjusted OR, 1.64; 95% CI, 1.13, 2.39), and hypertriglyceridemia (adjusted OR,
      1.56; 95% CI, 1.08, 2.28) were independently associated with all grades of LA.
      CONCLUSIONS: Metabolic syndrome (MetS) was significantly associated with every
      grade of leukoaraiosis (LA), including the minimal LA. Impaired fasting glucose
      and hypertriglyceridemia were associated with LA independently of elevated blood
      pressure. MetS can play an important role in identifying healthy subjects who
      have an increased risk of LA.

PMID- 17538034
TI  - Impairment of nonverbal recognition in Alzheimer disease: a PET O-15 study.
AB  - OBJECTIVE: To characterize deficits in nonverbal recognition memory and
      functional brain changes associated with these deficits in Alzheimer disease
      (AD). METHODS: Using O-15 PET, we studied 11 patients with AD and 17 cognitively
      intact elders during the combined encoding and retrieval periods of a nonverbal
      recognition task. Both task conditions involved recognition of line drawings of
      abstract shapes. In both conditions, subjects were first presented a list of
      shapes as study items, and then a list as test items, containing items from the
      study list and foils. In the titrated demand condition, the shape study list size
      (SLS) was adjusted prior to imaging so that each subject performed at
      approximately 75% recognition accuracy; difficulty during PET scanning in this
      condition was approximately matched across subjects. A control task was used in
      which SLS = 1 shape. RESULTS: During performance of the titrated demand
      condition, SLS averaged 4.55 (+/-1.86) shapes for patients with AD and 7.53 (+/
      4.81) for healthy elderly subjects (p = 0.031). However, both groups of subjects
      were closely matched on performance in the titrated demand condition during PET
      scanning with 72.17% (+/-7.98%) correct for patients with AD and 72.25% (+/
      7.03%) for elders (p = 0.979). PET results demonstrated that patients with AD
      showed greater mean differences between the titrated demand condition and control
      in areas including the left fusiform and inferior frontal regions (Brodmann areas
      19 and 45). CONCLUSIONS: Relative fusiform and inferior frontal differences may
      reflect the Alzheimer disease (AD) patients' compensatory engagement of alternate
      brain regions. The strategy used by patients with AD is likely to be a general
      mechanism of compensation, rather than task-specific.

PMID- 17538035
TI  - Development of systems of care for ST-elevation myocardial infarction patients:
      policy recommendations.

PMID- 17538036
TI  - Development of systems of care for ST-elevation myocardial infarction patients:
      gaps, barriers, and implications.

PMID- 17538037
TI  - Development of systems of care for ST-elevation myocardial infarction patients:
      evaluation and outcomes.

PMID- 17538038
TI  - Development of systems of care for ST-elevation myocardial infarction patients:
      the payer perspective.

PMID- 17538039
TI  - Development of systems of care for ST-elevation myocardial infarction patients:
      the primary percutaneous coronary intervention (ST-elevation myocardial
      infarction-receiving) hospital perspective.

PMID- 17538040
TI  - Development of systems of care for ST-elevation myocardial infarction patients:
      the non-percutaneous coronary intervention-capable (ST-elevation myocardial
      infarction referral) hospital perspective.

PMID- 17538041
TI  - Development of systems of care for ST-elevation myocardial infarction patients:
      the emergency medical services and emergency department perspective.

PMID- 17538042
TI  - Development of systems of care for ST-elevation myocardial infarction patients:
      the physician perspective.

PMID- 17538043
TI  - Development of systems of care for ST-elevation myocardial infarction patients:
      the patient and public perspective.

PMID- 17538044
TI  - Development of systems of care for ST-elevation myocardial infarction patients:
      current state of ST-elevation myocardial infarction care.

PMID- 17538045
TI  - Development of systems of care for ST-elevation myocardial infarction patients:
      executive summary.

PMID- 17538046
TI  - HIV counseling and testing among injection drug users needs to continue.

PMID- 17538047
TI  - Smoke before food: a tale of Baltimore City.

PMID- 17538048
TI  - The magnitude of key HIV prevention challenges in the United States: implications
      for a new national HIV prevention plan.
AB  - The Centers for Disease Control and Prevention has undertaken an advisory process
      to update its national HIV prevention plan. We offer observations on the
      magnitude of HIV prevention challenges in the United States and reflect on how
      these challenges might influence the structure of a new HIV prevention plan. We
      recommend a plan structure that (1) is based on fundamental principles of
      prevention, (2) enables accountability and mid-course correction, and (3) if
      achieved, would result in historic changes in the US HIV epidemic. The
      recommended plan structure would differentially prioritize serostatus
      determination and prevention and care interventions for people living with HIV
      while retaining goals directed at high-risk HIV-negative and general population
      members.

PMID- 17538049
TI  - Mortality of foreign-born and US-born Hispanic adults at younger ages: a
      reexamination of recent patterns.
AB  - OBJECTIVES: We sought to determine whether mortality rates among immigrant and US
      born Hispanic young adults were higher or lower compared with non-Hispanic
      Whites. We also sought to identify which causes of death accounted for the
      differences in mortality rates between groups. Measures. We used Texas and
      California vital registration data from 1999 to 2001 linked to 2000 census
      denominators. We calculated cause-specific, indirectly standardized rates and
      ratios and determined excess/deficit calculations comparing mortality rates among
      US- and foreign-born Hispanic men and women with rates among non-Hispanic White
      men and women. RESULTS: Mortality rates were substantially lower among Hispanic
      immigrant men (standardized mortality ratio [SMR]=0.79) and women (SMR=0.59) than
      among non-Hispanic White men and women. Most social and behavioral and chronic
      disease causes in Texas and California other than homicide were noteworthy
      contributors to this pattern. Mortality rates among US-born Hispanics were
      similar to or exceeded those among non-Hispanic Whites (male SMR=1.17, female
      SMR=0.91). CONCLUSIONS: Mortality rates among younger Hispanic immigrants in
      Texas and California were lower than rates among non-Hispanic Whites. This
      pattern was not observed among US-born Hispanics, however.

PMID- 17538050
TI  - The contribution of preterm birth to the Black-White infant mortality gap, 1990
      and 2000.
AB  - OBJECTIVES: We evaluated whether the decline of the racial disparity in preterm
      birth during the last decade was commensurate with a decline in the contribution
      of preterm birth to the infant mortality gap. METHODS: We used linked files of
      1990 and 2000 data on US infant births and deaths to partition the gap between
      Black and White infant mortality rates into differences in the (1) distribution
      of gestational age and (2) gestational age-specific mortality rates. RESULTS:
      Between 1990 and 2000, the Black-White infant mortality rate ratio did not change
      significantly (2.3 vs 2.4). Excess deaths among preterm Black infants accounted
      for nearly 80% of the Black-White infant mortality gap in both 1990 and 2000. The
      narrowing racial disparity in the preterm birth rate was counterbalanced by
      greater mortality reductions in White than in Black preterm infants. Extremely
      preterm birth (<28 weeks) was 4 times higher in Black infants and accounted for
      more than half of the infant mortality gap. CONCLUSIONS: Substantial reductions
      in the Black-White infant mortality gap will require improved prevention of
      extremely preterm birth among Black infants.

PMID- 17538051
TI  - Rethinking mandatory HIV testing during pregnancy in areas with high HIV
      prevalence rates: ethical and policy issues.
AB  - We analyzed the ethical and policy issues surrounding mandatory HIV testing of
      pregnant women in areas with high HIV prevalence rates. Through this analysis, we
      seek to demonstrate that a mandatory approach to testing and treatment has the
      potential to significantly reduce perinatal transmission of HIV and defend the
      view that mandatory testing is morally required if a number of conditions can be
      met. If such programs are to be introduced, continuing medical care, including
      highly active antiretroviral therapy, must be provided and pregnant women must
      have reasonable alternatives to compulsory testing and treatment. We propose that
      a liberal regime entailing abortion rights up to the point of fetal viability
      would satisfy these requirements. Pilot studies in the high-prevalence region of
      southern African countries should investigate the feasibility of this approach.

PMID- 17538052
TI  - Persistent clusters of mortality in the United States.
AB  - We explored how place shapes mortality by examining 35 consecutive years of US
      mortality data. Mapping age-adjusted county mortality rates showed both
      persistent temporal and spatial clustering of high and low mortality rates.
      Counties with high mortality rates and counties with low mortality rates both
      experienced younger population out-migration, had economic decline, and were
      predominantly rural. These mortality patterns have important implications for
      proper research model specification and for health resource allocation policies.

PMID- 17538053
TI  - The effects of acculturation on asthma burden in a community sample of Mexican
      American schoolchildren.
AB  - OBJECTIVES: We sought to determine whether low acculturation among Mexican
      American caregivers protects their children against asthma. METHODS: Data were
      obtained from an observational study of urban pediatric asthma. Dependent
      variables were children's diagnosed asthma and total (diagnosed plus possible)
      asthma. Regression models were controlled for caregivers' level of acculturation,
      education, marital status, depression, life stress, and social support and
      children's insurance. RESULTS: Caregivers' level of acculturation was associated
      with children's diagnosed asthma (P = .025) and total asthma (P = .078) in
      bivariate analyses. In multivariate models, protective effects of caregivers'
      level of acculturation were mediated by the other covariates. Independent
      predictors of increased diagnosed asthma included caregivers' life stress (odds
      ratio [OR] = 1.12, P= .005) and children's insurance, both public (OR = 4.71, P=
      .009) and private (OR = 2.87, P= .071). Only caregiver's life stress predicted
      increased total asthma (OR = 1.21, P= .001). CONCLUSIONS: The protective effect
      of caregivers' level of acculturation on diagnosed and total asthma for Mexican
      American children was mediated by social factors, especially caregivers' life
      stress. Among acculturation measures, foreign birth was more predictive of
      disease status than was language use or years in country. Increased acculturation
      among immigrant groups does not appear to lead to greater asthma risk.

PMID- 17538054
TI  - Hispanic paradox in biological risk profiles.
AB  - OBJECTIVES: We examined biological risk profiles by race, ethnicity, and nativity
      to evaluate evidence for a Hispanic paradox in measured health indicators.
      METHODS: We used data on adults aged 40 years and older (n = 4206) from the
      National Health and Nutrition Examination Surveys (1999-2002) to compare blood
      pressure, metabolic, and inflammatory risk profiles for Whites, Blacks, US-born
      and foreign-born Hispanics, and Hispanics of Mexican origin. We controlled for
      age, gender, and socioeconomic status. RESULTS: Hispanics have more risk factors
      above clinical risk levels than do Whites but fewer than Blacks. Differences
      between Hispanics and Whites disappeared after we controlled for socioeconomic
      status, but results differed by nativity. After we controlled for socioeconomic
      status, the differences between foreign-born Hispanics and Whites were
      eliminated, but US-born Mexican Americans still had higher biological risk scores
      than did both Whites and foreign-born Mexican Americans. CONCLUSIONS: There is no
      Hispanic paradox in biological risk profiles. However, our finding that foreign
      born Hispanics and Whites had similar biological risk profiles, but US-born
      Mexican Americans had higher risk, was consistent with hypothesized effects of
      migrant health selectivity (healthy people in-migrating and unhealthy people out
      migrating) as well as some differences in health behaviors between US-born and
      foreign-born Hispanics.

PMID- 17538055
TI  - A nationwide study of discrimination and chronic health conditions among Asian
      Americans.
AB  - OBJECTIVES: We examined whether self-reported everyday discrimination was
      associated with chronic health conditions among a nationally representative
      sample of Asian Americans. METHODS: Data were from the Asian American subsample
      (n = 2095) of the National Latino and Asian American Study conducted in 2002 and
      2003. Regression techniques (negative binomial and logistic) were used to examine
      the association between discrimination and chronic health conditions. Analyses
      were conducted for the entire sample and 3 Asian subgroups (Chinese, Vietnamese,
      and Filipino). RESULTS: Reports of everyday discrimination were associated with
      many chronic conditions, after we controlled for age, gender, region, per capita
      income, education, employment, and social desirability bias. Discrimination was
      also associated with indicators of heart disease, pain, and respiratory
      illnesses. There were some differences by Asian subgroup. CONCLUSIONS: Everyday
      discrimination may contribute to stress experienced by racial/ethnic minorities
      and could lead to chronic illness.

PMID- 17538056
TI  - Perpetration of intimate partner violence among men in methadone treatment
      programs in New York City.
AB  - This study examined the prevalence of perpetration of intimate partner violence
      among 356 men recruited from methadone maintenance treatment programs. We used
      logistic regression with covariance adjustment to examine the associations
      between intimate partner violence and illicit drug use by the participants, their
      female partners, or both. We found a high prevalence of intimate partner violence
      among the men in our sample. Significant associations between intimate partner
      violence and illicit drug use varied by types of drugs and whether the female
      partner or both partners were using drugs.

PMID- 17538057
TI  - The political economy of marriage and HIV: the ABC approach, "safe" infidelity,
      and managing moral risk in Uganda.
AB  - Research has shown that married women's greatest risk for HIV infection is their
      husbands' extramarital sexual activities. Using 6 months of ethnographic research
      in southeastern Uganda, I examined how the social and economic contexts
      surrounding men's extramarital sexuality and the dynamics of marriage put men and
      women at risk for HIV infection. I found that Uganda's HIV prevention messages
      may be inadvertently contributing to increased difficulty in acknowledging HIV
      risk and to newer forms of sexual secrecy and that structural determinants,
      including persistent poverty, intersect with gender inequalities to shape marital
      risk. After examining a community effort to regulate men's sexuality, I suggest
      that HIV prevention strategies should focus more on endogenous forms of risk
      reduction while simultaneously addressing structural factors that facilitate
      opportunities for men's extramarital sex.

PMID- 17538058
TI  - Parenting-related stressors and self-reported mental health of mothers with young
      children.
AB  - OBJECTIVES: We assessed whether there were associations between maternal mental
      health and individual and co-occurring parenting stressors related to social and
      financial factors and child health care access. METHODS: We used cross-sectional
      data from the 2000 National Survey of Early Childhood Health. The 5-item Mental
      Health Inventory was used to measure self-reported mental health. RESULTS: After
      we controlled for demographic covariates, we found that the following stressors
      increased the risk of poor maternal mental health: lack of emotional (odds ratio
      [OR] = 3.4; 95% confidence interval [CI] = 2.0, 5.9) or functional (OR=2.2; 95%
      CI=1.3, 3.7) social support for parenting, too much time spent with child
      (OR=3.5; 95% CI=2.0, 6.1), and difficulty paying for child care (OR=2.3; 95%
      CI=1.4, 3.9). In comparison with mothers without any parenting stressors, mothers
      reporting 1 stressor had 3 times the odds of poor mental health (OR = 3.1; 95% CI
      = 2.1, 4.8), and mothers reporting 2 or more stressors had nearly 12 times the
      odds (OR = 11.7; 95% CI = 7.1, 19.3). CONCLUSIONS: If parenting stressors such as
      those examined here are to be addressed, changes may be required in community
      support systems, and improvements in relevant social policies may be needed.

PMID- 17538059
TI  - The influence of social context on changes in fruit and vegetable consumption:
      results of the healthy directions studies.
AB  - As part of the Harvard Cancer Prevention Program Project, we used a social
      contextual model of health behavior change to test an intervention targeting
      multiple risk-related behaviors in working-class, multiethnic populations. We
      examined the relationships between the social contextual factors in our
      conceptual model and changes in fruit and vegetable consumption from baseline to
      completion of intervention in health centers and small business studies. We
      analyzed change in fruit and vegetable consumption, measured at baseline and
      final assessments by self-report, in 2 randomized controlled prevention trials: 1
      in small businesses (n = 974) and 1 in health centers (n = 1954). Stronger social
      networks, social norms that were more supportive, food sufficiency, and less
      household crowding were associated with greater change in fruit and vegetable
      intake. We also observed differences between our intervention sites. Social
      context can play an important role in promoting changes in fruit and vegetable
      consumption.

PMID- 17538060
TI  - Public health surveillance of fatal child maltreatment: analysis of 3 state
      programs.
AB  - OBJECTIVES: We sought to describe approaches to surveillance of fatal child
      maltreatment and to identify options for improving case ascertainment. METHODS:
      Three states--California, Michigan, and Rhode Island--used multiple data sources
      for surveillance. Potential cases were identified, operational definitions were
      applied, and the number of maltreatment deaths was determined. RESULTS: These
      programs identified 258 maltreatment deaths in California, 192 in Michigan, and
      60 in Rhode Island. Corresponding maltreatment fatality rates ranged from 2.5 per
      100,000 population in Michigan to 8.8 in Rhode Island. Most deaths were
      identified by child death review teams in Rhode Island (98%), Uniform Crime
      Reports in California (56%), and child welfare agency data in Michigan (44%).
      Compared with the total number of cases identified, child welfare agency (the
      official source for maltreatment reports) and death certificate data
      underascertain child maltreatment deaths by 55% to 76% and 80% to 90%,
      respectively. In all 3 states, more than 90% of cases ascertained could be
      identified by combining 2 data sources. CONCLUSIONS: No single data source was
      adequate for thorough surveillance of fatal child maltreatment, but combining
      just 2 sources substantially increased case ascertainment. The child death review
      team process may be the most promising surveillance approach.

PMID- 17538061
TI  - Circumstances of first injection among illicit drug users accessing a medically
      supervised safer injection facility.
AB  - There have been concerns that safer injecting facilities may promote initiation
      into injection drug use. We examined length of injecting career and circumstances
      surrounding initiation into injection drug use among 1065 users of North
      America's first safer injecting facility and found that the median years of
      injection drug use were 15.9 years, and that only 1 individual reported
      performing a first injection at the safer injecting facility. These findings
      indicate that the safer injecting facility's benefits have not been offset by a
      rise in initiation into injection drug use.

PMID- 17538062
TI  - Predictors of condom use among young adults in South Africa: the Reproductive
      Health and HIV Research Unit National Youth Survey.
AB  - OBJECTIVES: We examined correlates of condom use among a national random
      probability sample of sexually experienced young adults aged 15 to 24 years (n =
      7686) in South Africa. METHODS: Using data from the Reproductive Health and HIV
      Research Unit National Youth Survey, we conducted gender-stratified bivariate and
      multivariate logistic regression analyses to determine predictors of whether
      respondents had used a condom during their most recent sexual intercourse.
      RESULTS: Condom use at sexual debut and talking with one's first sexual partner
      about condoms were the most significant predictors of condom use at most recent
      intercourse. Other significant predictors included high condom use self-efficacy,
      optimism about the future, and reported behavior change attributable to HIV/AIDS.
      Young adults who were married or had been involved in a relationship for 6 months
      or more were significantly less likely to have used a condom during their most
      recent sexual intercourse. CONCLUSIONS: Our findings point to the importance of
      exposing youths to sexuality education before their sexual debut as well as
      voluntary counseling and testing and programming that supports young adults,
      particularly young women, in making informed decisions about sexual intercourse
      and condoms.

PMID- 17538063
TI  - Young incarcerated men's perceptions of and experiences with HIV testing.
AB  - We analyzed incarcerated men's perceptions of and experiences with HIV testing.
      Interviews were conducted with 105 men, aged 18 to 29 years, in 4 states. Most
      men had received an HIV test while incarcerated because it was convenient or free
      or because they thought it was mandatory. At most sites, men believed they were
      HIV-negative because they never received test results. Some men did not know the
      diseases for which they had been tested. Some men avoided HIV testing outside
      prison because they lacked time, lacked resources, feared knowing the results, or
      perceived themselves to not be at risk. HIV testing programs for young men inside
      or outside prison should address barriers to HIV testing, communicate the meaning
      and extent of testing, and improve notification of those with HIV-negative
      results.

PMID- 17538064
TI  - The impact of safer breastfeeding practices on postnatal HIV-1 transmission in
      Zimbabwe.
AB  - OBJECTIVES: We assessed the association between exposure to an educational
      intervention that emphasized safer breastfeeding practices and postnatal HIV
      transmission among 437 HIV-positive mothers in Zimbabwe, 365 of whom did not know
      their infection status. METHODS: Mothers were tested for HIV and were encouraged-
      but not required--to learn their HIV status. Intervention exposure was assessed
      by a questionnaire, Turnbull methods were used to estimate postnatal HIV
      transmission, and multivariate Cox proportional hazard models were constructed to
      assess the association between intervention exposure and postnatal HIV
      transmission. RESULTS: Cumulative postnatal HIV transmission was 8.2%; each
      additional intervention contact was associated with a 38% reduction in postnatal
      HIV transmission. HIV-positive mothers who were exposed to both print and video
      materials were 79% less likely to infect their infants compared with mothers who
      had no exposure. These findings were similar for mothers who did not know their
      HIV status. CONCLUSIONS: The promotion of exclusive breastfeeding has the
      potential to reduce postnatal HIV transmission among women who do not know their
      HIV status, and child survival and HIV prevention programs should support this
      practice.

PMID- 17538065
TI  - Partner violence screening in rural health care clinics.
AB  - OBJECTIVES: We sought to determine the frequency of intimate partner violence by
      type in a large, clinic-based, nurse-administered screening and services
      intervention project. METHODS: A brief intimate partner violence screen, which
      included items to measure sexual and physical assaults and psychological
      battering (using the Women's Experience With Battering scale) was administered to
      consenting women receiving care at 1 of 8 rural clinics in South Carolina.
      RESULTS: Between April 2002 and August 2005, 4945 eligible women were offered
      intimate partner violence screening, to which 3664 (74.1%) consented. Prevalence
      of intimate partner violence in a current (ongoing) relationship was 13.3%, and
      939 women (25.6%) had experienced intimate partner violence at some point in the
      past 5 years. Of those ever experiencing intimate partner violence, the majority
      (65.6%) experienced both assaults and psychological battering; 10.1% experienced
      assault only, and 24.3% experienced psychological battering only. Most women
      (85.5%) currently experiencing both psychological battering and assaults stated
      that violence was a problem in their current relationship. CONCLUSIONS: The
      intimate partner violence screening technique we used was feasible to implement,
      acceptable to women seeking health care at the targeted clinics, and indicated a
      high proportion of women reporting intimate partner violence in the past 5 years,
      with a majority of those women stating that such violence was a problem in their
      relationships. These findings demonstrated the viability of the screening
      technique, which supports the growing importance of implementing intimate partner
      violence screenings in clinical settings in order to reduce the prevalence of
      violence in intimate relationships.

PMID- 17538066
TI  - Overt and subtle racial discrimination and mental health: preliminary findings
      for Korean immigrants.
AB  - OBJECTIVES: We examined differential effects of overt and subtle forms of racial
      discrimination on 2 dimensions of mental health-positive affect and depressive
      symptoms, and explored the mediating roles of emotional arousal and cognitive
      appraisal. METHODS: Cross-sectional survey data were collected through face-to
      face interviews with a sample (N=180) of adult Korean immigrants living in
      Toronto, Ontario. Maximum likelihood estimates of path coefficients were obtained
      using structural equation models. RESULTS: Perceived racial discrimination was
      associated with both the erosion of positive affect and depressive symptoms.
      Overt discrimination was associated with the erosion of positive affect, and
      subtle discrimination was associated with depressive symptoms. Effects of subtle
      discrimination on depressive symptoms were mediated through cognitive appraisal.
      CONCLUSIONS: The results emphasize the salience of subtle discrimination for the
      mental health of Asian immigrants. Experiences of overt racial bias seemed to be
      of little importance for the levels of depressive symptoms among those in our
      sample, although the experience of blatant discrimination tended to reduce
      positive mood.

PMID- 17538067
TI  - Securing maternal health through comprehensive reproductive health services:
      lessons from Bangladesh.
AB  - During the past decade, there has been a noticeable reduction of maternal
      mortality in Bangladesh, in part because of government policy and program
      initiatives. Of particular note is the comprehensive reproductive health strategy
      adopted in 1996 under the country's first Health and Population Sector Strategy
      and the 5-year Health and Population Sector Programme (1998-2003). The latter
      includes actions in most of the areas recommended in the World Health
      Organization's 2004 report, Reproductive Health Strategy to Accelerate Progress
      Towards the Attainment of International Development Goals and Targets. After
      assessing Bangladesh's achievements and challenges in the design and
      implementation of a maternal health strategy, I concluded that mobilizing and
      nurturing political will is the key to sustaining policy commitment to
      comprehensive reproductive health.

PMID- 17538068
TI  - Approval of syringe exchange programs in California: results from a local
      approach to HIV prevention.
AB  - OBJECTIVES: We studied the effect of local approval of syringe exchange programs
      in California (through Assembly AB136) on program availability and performance.
      METHODS: We determined the number of active syringe exchange programs in
      California by conducting Internet searches and obtaining information from the
      state and from local programs. To track changes in program availability and
      performance between 2000 and 2002, we interviewed 24 program directors annually
      for 3 years about program characteristics, syringe exchange policies, law
      enforcement contact, and other issues. We conducted multivariate analyses to
      determine whether AB136 approval status was associated with changes in
      performance. RESULTS: Fifteen local governments (13 counties and 2 cities)
      enacted the new law by 2002, and operating syringe exchange programs increased
      from 24 to 35. The proportion of these programs that were not locally approved
      declined from 54% to 40%. No new approved programs were started in high-need
      counties. Total syringes exchanged increased by more than 1 million per year,
      average annual budgets increased by more than 50%, and police harassment of the
      program volunteers, clients, and operators declined. Improvements at approved
      syringe exchange programs accounted for these changes. CONCLUSIONS: Statewide
      approval and funding appears necessary to further syringe exchange availability
      in California.

PMID- 17538069
TI  - Racial/ethnic differences in physician distrust in the United States.
AB  - OBJECTIVES: We examined the racial/ethnic and geographic variation in distrust of
      physicians in the United States. METHODS: We obtained data from the Community
      Tracking Study, analyzing 20 sites where at least 5% of the population was
      Hispanic and 5% was Black. RESULTS: In univariate analyses, Blacks and Hispanics
      reported higher levels of physician distrust than did Whites. Multivariate
      analyses, however, suggested a complex interaction among sociodemographic
      variables, city of residence, race/ethnicity, and distrust of physician. In
      general, lower socioeconomic status (defined as lower income, lower education,
      and no health insurance) was associated with higher levels of distrust, with men
      generally reporting more distrust than women. But the strength of these effects
      was modified by race/ethnicity. We present examples of individual cities in which
      Blacks reported consistently higher mean levels of distrust than did Whites,
      consistently lower mean levels of distrust than did Whites, or a mixed
      relationship dependent on socioeconomic status. In the same cities, Hispanics
      reported either consistently higher mean levels of distrust relative to Whites or
      a mixed relationship. CONCLUSIONS: Racial/ethnic differences in physician
      distrust are less uniform than previously hypothesized, with substantial
      geographic and individual variation present.

PMID- 17538070
TI  - Framing HIV prevention discourse to encompass the complexities of war in northern
      Uganda.
AB  - In northern Uganda, physical and structural violence (political repression,
      economic inequality, and gender-based discrimination) increase vulnerability to
      HIV infection. In settings of war, traditional HIV prevention that solely
      promotes risk avoidance and risk reduction and assumes the existence of personal
      choice inadequately addresses the realities of HIV transmission. The design of
      HIV prevention strategies in northern Uganda must recognize how HIV transmission
      occurs and the factors that put people at risk for infection. A human rights
      approach provides a viable model for achieving this aim.

PMID- 17538071
TI  - Contextual influences on modern contraceptive use in sub-Saharan Africa.
AB  - OBJECTIVES: We examined the role of community-level factors in explaining
      geographic variations in modern contraceptive use in 6 African countries.
      METHODS: We analyzed Demographic and Health Survey and contextual data sources
      with multilevel modeling techniques to identify factors contributing to
      geographic variations in women's use of modern contraceptives. RESULTS: We found
      significant associations between several community-level factors and reported use
      of modern contraceptive methods. We also identified several pathways of influence
      between the community and the individual. CONCLUSIONS: Aspects of a community's
      sociocultural and economic environment appear to influence a woman's use of
      modern contraceptive methods.

PMID- 17538072
TI  - Marijuana initiation in 2 American Indian reservation communities: comparison
      with a national sample.
AB  - OBJECTIVES: We examined disparities in age-related patterns of marijuana
      initiation in 2 culturally distinct American Indian reservation communities (from
      the Northern Plains and the Southwest) compared with a national sample. METHODS:
      We used discrete-time survival models to estimate age-related risk for initiation
      with data from 2 population-based studies: the American Indian Service
      Utilization, Psychiatric Epidemiology, Risk and Protective Factors Project and
      the baseline National Comorbidity Survey. RESULTS: Among respondents who were
      born before 1960, peak risk for marijuana initiation in all samples was at age 18
      years, and risk was greatest in the national sample. Among those who were born
      later than 1960, risk peaked at age 16 years and was highest in the American
      Indian samples. Males were at increased risk compared with females, especially in
      the older cohort and the Southwest tribal sample. CONCLUSIONS: Findings of
      disproportionate risk for marijuana initiation among younger members of the
      tribal samples raise concerns that American Indian reservation youths may be
      increasingly vulnerable to drug use and its concomitants, which suggests a need
      for more aggressive prevention efforts in these communities.

PMID- 17538073
TI  - Disparities in infant mortality: what's genetics got to do with it?
AB  - Since 1950, dramatic advances in human genetics have occurred, racial disparities
      in infant mortality have widened, and the United States' international ranking in
      infant mortality has deteriorated. The quest for a "preterm birth gene" to
      explain racial differences is now under way. Scores of papers linking
      polymorphisms to preterm birth have appeared in the past few years. Is this
      strategy likely to reduce racial disparities? We reviewed broad epidemiological
      patterns that call this approach into question. Overall patterns of racial
      disparities in mortality and secular changes in rates of prematurity as well as
      birth-weight patterns in infants of African immigrant populations contradict the
      genetic theory of race and point toward social mechanisms. We postulate that a
      causal link to class disparities in health exists.

PMID- 17538074
TI  - Public health and social ideas in modern Brazil.
AB  - Public health in Brazil achieved remarkable development at the turn of the 20th
      century thanks in part to physicians and social thinkers who made it central to
      their proposals for "modernizing" the country. Public health was more than a set
      of medical and technical measures; it was fundamental to the project of nation
      building. I trace the interplay between public health and social ideas in the
      late 19th and early 20th centuries. Physicians and social thinkers challenged the
      traditional belief that Brazil's sociocultural and ethnic diversity was an
      obstacle to modernization, and they promoted public health as the best
      prescription for national unity. Public health ideas in developing countries such
      as Brazil may have a greater impact when they are intertwined with social thought
      and with the processes of nation building and construction of a modern society.

PMID- 17538075
TI  - Maternal pentraxin 3 deficiency compromises implantation in mice.
AB  - Reduced litter sizes in mice missing pentraxin 3 (Ptx3) have been attributed to
      fertilization failure. However, our global gene expression studies showed high
      uterine Ptx3 expression at the implantation site in mice, suggesting its role in
      blastocyst implantation. We initiated molecular and genetic studies in mice to
      explore the importance of uterine Ptx3 in this process. We found that Ptx3 is
      expressed in a unique and transient fashion at implantation sites. With the
      initiation of implantation on midnight of Day 4 of pregnancy, Ptx3 is expressed
      exclusively in stromal cells at the site of blastocysts. On Day 5, its expression
      is more intense in decidualizing stromal cells, but it disappears on Day 6. The
      expression again becomes evident in the deciduum on Day 7, followed by a more
      robust expression on Day 8, particularly at the antimesometrial pole. From Day 9,
      with the initiation of placentation, Ptx3 expression becomes undetectable. These
      results suggest a role for PTX3 in implantation and decidualization. Indeed,
      deletion of Ptx3 results in both compromised implantation and decidualization.
      Interleukin 1B (IL1B), a known inducer of Ptx3, is also transiently expressed in
      stromal cells at the implantation site, suggesting that IL1B is an inducer of
      uterine Ptx3 expression. In fact, uterine Ptx3 expression follows that of Il1b
      induced by lipopolysaccharide treatment on Day 7 of pregnancy. Collectively,
      these findings provide evidence for an important role for PTX3 in implantation
      and decidualization. This study has clinical implications, since PTX3 is
      expressed in the receptive endometrium, and trophoblast cells influence decidual
      Ptx3 expression in humans.

PMID- 17538076
TI  - Regulation of 17-beta hydroxysteroid dehydrogenase type 2 in human placental
      endothelial cells.
AB  - 17-beta hydroxysteroid dehydrogenase type 2 (HSD17B2) oxidizes estradiol to
      estrone, testosterone to androstenedione, and 20 alpha-dihydroprogesterone to
      progesterone. HSD17B2 is highly expressed in human placental tissue where it is
      localized to placental endothelial cells lining the fetal compartment. The aim of
      this study was to investigate the effects of potential regulatory factors
      including progesterone, estradiol, and retinoic acid (RA) onHSD17B2 expression in
      primary human placental endothelial cells in culture.HSD17B2 mRNA expression was
      not regulated by progesterone, the progesterone agonist R5020, or estradiol
      treatment. RA significantly induced HSD17B2 mRNA levels and enzyme activity in a
      dose- and time-dependent manner. Maximal stimulation occurred at Hour 48 at an RA
      concentration of 10(-6) M. Both retinoic acid receptor alpha (RARA) and retinoid
      X receptor alpha (RXRA) were readily detected by immunoblotting in isolated
      placental endothelial cells. RNA interference directed against RARA or RXRA led
      to reduced basal levels of HSD17B2 mRNA levels and significantly abolished RA
      stimulated HSD17B2 expression. Together, these data indicate that regulation of
      HSD17B2 mRNA levels and enzymatic activity by RA in the placenta is mediated by
      RARA and RXRA.

PMID- 17538077
TI  - Profiles in patient safety: A "perfect storm" in the emergency department.
AB  - Correct and rapid diagnosis is pivotal to the practice of emergency medicine, yet
      the chaotic and ill-structured emergency department environment is fertile ground
      for the commission of diagnostic error. Errors may result from specific error
      producing conditions (EPCs) or, more frequently, from an interaction between such
      conditions. These EPCs are often expedient and serve to shorten the decision
      making process in a high-pressure environment. Recognizing that they will
      inevitably exist, it is important for clinicians to understand and manage their
      dangers. The authors present a case of delayed diagnosis resulting from the
      interaction of a number of EPCs that produced a "perfect" situation to produce a
      missed or delayed diagnosis. They offer practical suggestions whereby clinicians
      may decrease their chances of becoming victims of these influences.

PMID- 17538078
TI  - Advanced statistics: missing data in clinical research--part 1: an introduction
      and conceptual framework.
AB  - Missing data are commonly encountered in clinical research. Unfortunately, they
      are often neglected or not properly handled during analytic procedures, and this
      may substantially bias the results of the study, reduce study power, and lead to
      invalid conclusions. In this two-part series, the authors will introduce key
      concepts regarding missing data in clinical research, provide a conceptual
      framework for how to approach missing data in this setting, describe typical
      mechanisms and patterns of censoring of data and their relationships to specific
      methods of handling incomplete data, and describe in detail several simple and
      more complex methods of handling such data. In part 1, the authors will describe
      relatively simple approaches to handling missing data, including complete-case
      analysis, available-case analysis, and several forms of single imputation,
      including mean imputation, regression imputation, hot and cold deck imputation,
      last observation carried forward, and worst case analysis. In part 2, the authors
      will describe in detail multiple imputation, a more sophisticated and valid
      method for handling missing data.

PMID- 17538079
TI  - Uncovering HIV infection in the emergency department: a broader perspective.

PMID- 17538080
TI  - Gender bias in cardiovascular testing persists after adjustment for presenting
      characteristics and cardiac risk.
AB  - OBJECTIVES: Previous studies have found that female patients receive fewer
      invasive tests for cardiovascular disease than male patients. The authors
      assessed whether different clinical characteristics at emergency department
      presentation account for this gender bias. METHODS: Patients with potential acute
      coronary syndrome (ACS) who presented to a university hospital were prospectively
      identified. A structured data instrument that included demographic information,
      chest pain description, history, physical examination, chest radiography, and
      electrocardiogram (ECG) data was completed. Hospital course was tracked daily.
      Patients received 30-day telephone follow-up. The main outcome was whether the
      patients received objective evaluation for coronary artery disease after
      adjustment for cardiac risk, including race, age, total number of risk factors,
      Thrombolysis in Myocardial Infarction (TIMI) score, ECG, and whether the patient
      sustained an acute myocardial infarction on index hospitalization. RESULTS: There
      were 3,514 women (58%) and 2,547 men (42%) studied. They had similar presenting
      characteristics: chest pain quality (pressure/tightness: female 60% vs. male 59%,
      p = 0.6), location (substernal: female 82% vs. male 80%; p = 0.2), radiation
      (female 27% vs. male 26%; p = 0.3), and most associated symptoms. Men had more
      cardiac risk factors (mean 1.5 vs 1.4; p < 0.001), more abnormal ECGs (59% vs.
      48%; p < 0.001), and a higher TIMI risk score (p < 0.001). With respect to the
      main outcome, men received more cardiac catheterizations (12.6% vs. 6.0%; odds
      ratio [OR], 2.25; 95% confidence interval [CI] = 1.88 to 2.70) and more stress
      tests (14.7% vs. 12.3%; OR, 1.22; 95% CI = 1.05 to 1.42). After adjustment for
      age, race, cardiac risk factors, ECG, and TIMI risk score, men still received
      more cardiac catheterizations (adjusted OR, 1.72; 95% CI = 1.40 to 2.11) and
      stress tests (adjusted OR, 1.16; 95% CI = 1.01 to 1.33). Models adjusting for
      acute myocardial infarction or death, high-risk initial clinical impression, or
      emergency department disposition found similar results for increased likelihood
      of cardiac catheterization in men but no difference in stress testing between men
      and women. CONCLUSIONS: Female patients with potential ACS receive fewer cardiac
      catheterizations than male patients, even when presenting complaint, history,
      ECG, and diagnosis are taken into account. The gender bias cannot be explained by
      differences in presentation or clinical course.

PMID- 17538081
TI  - Images in clinical medicine. Putaminal necrosis.

PMID- 17538082
TI  - The legacy of World Trade Center dust.

PMID- 17538083
TI  - Back surgery--who needs it?

PMID- 17538084
TI  - Surgery versus prolonged conservative treatment for sciatica.
AB  - BACKGROUND: Lumbar-disk surgery often is performed in patients who have sciatica
      that does not resolve within 6 weeks, but the optimal timing of surgery is not
      known. METHODS: We randomly assigned 283 patients who had had severe sciatica for
      6 to 12 weeks to early surgery or to prolonged conservative treatment with
      surgery if needed. The primary outcomes were the score on the Roland Disability
      Questionnaire, the score on the visual-analogue scale for leg pain, and the
      patient's report of perceived recovery during the first year after randomization.
      Repeated-measures analysis according to the intention-to-treat principle was used
      to estimate the outcome curves for both groups. RESULTS: Of 141 patients assigned
      to undergo early surgery, 125 (89%) underwent microdiskectomy after a mean of 2.2
      weeks. Of 142 patients designated for conservative treatment, 55 (39%) were
      treated surgically after a mean of 18.7 weeks. There was no significant overall
      difference in disability scores during the first year (P=0.13). Relief of leg
      pain was faster for patients assigned to early surgery (P<0.001). Patients
      assigned to early surgery also reported a faster rate of perceived recovery
      (hazard ratio, 1.97; 95% confidence interval, 1.72 to 2.22; P<0.001). In both
      groups, however, the probability of perceived recovery after 1 year of follow-up
      was 95%. CONCLUSIONS: The 1-year outcomes were similar for patients assigned to
      early surgery and those assigned to conservative treatment with eventual surgery
      if needed, but the rates of pain relief and of perceived recovery were faster for
      those assigned to early surgery. (Current Controlled Trials number,
      ISRCTN26872154 [controlled-trials.com].).

PMID- 17538085
TI  - Surgical versus nonsurgical treatment for lumbar degenerative spondylolisthesis.
AB  - BACKGROUND: Management of degenerative spondylolisthesis with spinal stenosis is
      controversial. Surgery is widely used, but its effectiveness in comparison with
      that of nonsurgical treatment has not been demonstrated in controlled trials.
      METHODS: Surgical candidates from 13 centers in 11 U.S. states who had at least
      12 weeks of symptoms and image-confirmed degenerative spondylolisthesis were
      offered enrollment in a randomized cohort or an observational cohort. Treatment
      was standard decompressive laminectomy (with or without fusion) or usual
      nonsurgical care. The primary outcome measures were the Medical Outcomes Study 36
      Item Short-Form General Health Survey (SF-36) bodily pain and physical function
      scores (100-point scales, with higher scores indicating less severe symptoms) and
      the modified Oswestry Disability Index (100-point scale, with lower scores
      indicating less severe symptoms) at 6 weeks, 3 months, 6 months, 1 year, and 2
      years. RESULTS: We enrolled 304 patients in the randomized cohort and 303 in the
      observational cohort. The baseline characteristics of the two cohorts were
      similar. The one-year crossover rates were high in the randomized cohort
      (approximately 40% in each direction) but moderate in the observational cohort
      (17% crossover to surgery and 3% crossover to nonsurgical care). The intention-to
      treat analysis for the randomized cohort showed no statistically significant
      effects for the primary outcomes. The as-treated analysis for both cohorts
      combined showed a significant advantage for surgery at 3 months that increased at
      1 year and diminished only slightly at 2 years. The treatment effects at 2 years
      were 18.1 for bodily pain (95% confidence interval [CI], 14.5 to 21.7), 18.3 for
      physical function (95% CI, 14.6 to 21.9), and -16.7 for the Oswestry Disability
      Index (95% CI, -19.5 to -13.9). There was little evidence of harm from either
      treatment. CONCLUSIONS: In nonrandomized as-treated comparisons with careful
      control for potentially confounding baseline factors, patients with degenerative
      spondylolisthesis and spinal stenosis treated surgically showed substantially
      greater improvement in pain and function during a period of 2 years than patients
      treated nonsurgically. (ClinicalTrials.gov number, NCT00000409
      [ClinicalTrials.gov].).

PMID- 17538086
TI  - Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma.
AB  - BACKGROUND: Interferon alfa is widely used for metastatic renal-cell carcinoma
      but has limited efficacy and tolerability. Temsirolimus, a specific inhibitor of
      the mammalian target of rapamycin kinase, may benefit patients with this disease.
      METHODS: In this multicenter, phase 3 trial, we randomly assigned 626 patients
      with previously untreated, poor-prognosis metastatic renal-cell carcinoma to
      receive 25 mg of intravenous temsirolimus weekly, 3 million U of interferon alfa
      (with an increase to 18 million U) subcutaneously three times weekly, or
      combination therapy with 15 mg of temsirolimus weekly plus 6 million U of
      interferon alfa three times weekly. The primary end point was overall survival in
      comparisons of the temsirolimus group and the combination-therapy group with the
      interferon group. RESULTS: Patients who received temsirolimus alone had longer
      overall survival (hazard ratio for death, 0.73; 95% confidence interval [CI],
      0.58 to 0.92; P=0.008) and progression-free survival (P<0.001) than did patients
      who received interferon alone. Overall survival in the combination-therapy group
      did not differ significantly from that in the interferon group (hazard ratio,
      0.96; 95% CI, 0.76 to 1.20; P=0.70). Median overall survival times in the
      interferon group, the temsirolimus group, and the combination-therapy group were
      7.3, 10.9, and 8.4 months, respectively. Rash, peripheral edema, hyperglycemia,
      and hyperlipidemia were more common in the temsirolimus group, whereas asthenia
      was more common in the interferon group. There were fewer patients with serious
      adverse events in the temsirolimus group than in the interferon group (P=0.02).
      CONCLUSIONS: As compared with interferon alfa, temsirolimus improved overall
      survival among patients with metastatic renal-cell carcinoma and a poor
      prognosis. The addition of temsirolimus to interferon did not improve survival.
      (ClinicalTrials.gov number, NCT00065468 [ClinicalTrials.gov].).

PMID- 17538087
TI  - Survival after treatment with phenylacetate and benzoate for urea-cycle
      disorders.
AB  - BACKGROUND: The combination of intravenous sodium phenylacetate and sodium
      benzoate has been shown to lower plasma ammonium levels and improve survival in
      small cohorts of patients with historically lethal urea-cycle enzyme defects.
      METHODS: We report the results of a 25-year, open-label, uncontrolled study of
      sodium phenylacetate and sodium benzoate therapy (Ammonul, Ucyclyd Pharma) in 299
      patients with urea-cycle disorders in whom there were 1181 episodes of acute
      hyperammonemia. RESULTS: Overall survival was 84% (250 of 299 patients). Ninety
      six percent of the patients survived episodes of hyperammonemia (1132 of 1181
      episodes). Patients over 30 days of age were more likely than neonates to survive
      an episode (98% vs. 73%, P<0.001). Patients 12 or more years of age (93
      patients), who had 437 episodes, were more likely than all younger patients to
      survive (99%, P<0.001). Eighty-one percent of patients who were comatose at
      admission survived. Patients less than 30 days of age with a peak ammonium level
      above 1000 micromol per liter (1804 microg per deciliter) were least likely to
      survive a hyperammonemic episode (38%, P<0.001). Dialysis was also used in 56
      neonates during 60% of episodes and in 80 patients 30 days of age or older during
      7% of episodes. CONCLUSIONS: Prompt recognition of a urea-cycle disorder and
      treatment with both sodium phenylacetate and sodium benzoate, in conjunction with
      other therapies, such as intravenous arginine hydrochloride and the provision of
      adequate calories to prevent catabolism, effectively lower plasma ammonium levels
      and result in survival in the majority of patients. Hemodialysis may also be
      needed to control hyperammonemia, especially in neonates and older patients who
      do not have a response to intravenous sodium phenylacetate and sodium benzoate.

PMID- 17538089
TI  - Prevention and treatment of major blood loss.

PMID- 17538090
TI  - Images in clinical medicine. "Staging" pneumothorax.

PMID- 17538088
TI  - Clinical practice. Osteopenia.

PMID- 17538091
TI  - Case records of the Massachusetts General Hospital. Case 17-2007. A 25-year-old
      woman with relapsing fevers and recent onset of dyspnea.

PMID- 17538092
TI  - Alternative-pathway therapy for hyperammonemia.

PMID- 17538093
TI  - HSV therapy and HIV-1 reduction.

PMID- 17538094
TI  - Coronary microvascular dysfunction.

PMID- 17538095
TI  - Perioperative stroke.

PMID- 17538096
TI  - Medical mystery: skin discolorations--the answer.

PMID- 17538097
TI  - Case 3-2007: a boy with respiratory insufficiency.

PMID- 17538098
TI  - Macrocytosis and cobalamin deficiency in patients treated with sunitinib.

PMID- 17538099
TI  - Temporal intraspeech masking of plosive bursts: effects of hearing loss and
      frequency shaping.
AB  - PURPOSE: The purposes were (a) to compare masking of consonant bursts by adjacent
      vowels for listeners with and without hearing loss and (b) to determine the
      extent to which the temporal intraspeech masking can be reduced by a simulated
      hearing-aid frequency-response shaping. METHOD: Fourteen adults with
      sensorineural hearing loss and 10 with normal hearing participated. Seven of the
      participants with hearing loss had flat or gradually sloping audiograms, and 7
      had steeply sloping losses. Stimuli consisted of 3 consonant bursts (/t/, /p/,
      /k/) presented in isolation and in vowel-consonant-vowel combinations using the
      vowel /a/ with formant transition information removed. Normal-hearing listeners
      were tested using unfiltered stimuli. Listeners with hearing loss were tested
      using unfiltered stimuli and stimuli filtered to approximate a hearing aid
      frequency response prescribed by NAL-R. All listeners were tested under earphones
      at the most comfortable level for the vowel stimulus. Temporal intraspeech
      masking was quantified as the threshold shift produced by the adjacent vowels.
      RESULTS: Average intraspeech masking for listeners with steeply sloping hearing
      loss was significantly higher than that of normal-hearing listeners and those
      with flat/gradually sloping losses. Greater intraspeech masking was observed for
      /t/ and /p/ than for /k/. On average, frequency shaping significantly reduced the
      amount of intraspeech masking for listeners with steeply sloping hearing losses.
      Even with appropriate amplification/spectral shaping, however, temporal
      intraspeech masking remained greater than normal for several individuals.
      CONCLUSION: Findings suggest that some individuals with steeply sloping losses
      may need additional signal processing to supplement frequency shaping to overcome
      the effect of temporal intraspeech masking.

PMID- 17538100
TI  - Effects of cueing in auditory temporal masking.
AB  - PURPOSE: In a landmark study, B. A. Wright et al. (1997) reported an apparent
      backward-masking deficit in language-learning-impaired children. Subsequently,
      the controversial interpretation of those results has been influential in guiding
      treatments for childhood language problems. This study revisited the temporal
      masking paradigm reported by B. A. Wright et al. to evaluate adult listener
      signal/masker uncertainty effects for some of their key stimulus conditions. New
      signal conditions presented off frequency from the masker also were evaluated to
      assess conditions of reduced signal/masker confusion. METHOD: Masked detection
      was measured for 20-ms sinusoids (480, 1000, or 1680 Hz) presented at temporal
      positions before, during, or after a gated narrowband (bandwidth = 600-1400 Hz)
      masker. Listener uncertainty was investigated by cueing various stimulus temporal
      properties with a 6000-Hz sinusoid presented contralateral to the test ear.
      RESULTS: The primary cueing effect was measured in the backward-masking condition
      for the cue gated simultaneously with the on-frequency 1000-Hz signal. The
      resulting cued masked-detection threshold was reduced to quiet threshold. No
      significant cueing effects were obtained for other signal temporal positions in
      the masker or for any off-frequency signal conditions. CONCLUSIONS: These results
      for normal adult listeners indicate that on-frequency backward masking can be
      eliminated by cueing the signal, and thus, these findings raise the possibility
      that the deficit reported by B. A. Wright et al. for language-learning-impaired
      children may reflect inordinate signal/masker confusion, rather than a temporal
      processing deficit per se.

PMID- 17538101
TI  - The development of the text reception threshold test: a visual analogue of the
      speech reception threshold test.
AB  - PURPOSE: In this study, the authors aimed to develop a visual analogue of the
      widely used Speech Reception Threshold (SRT; R. Plomp & A. M. Mimpen, 1979b)
      test. The Text Reception Threshold (TRT) test, in which visually presented
      sentences are masked by a bar pattern, enables the quantification of modality
      aspecific variance in speech-in-noise comprehension to obtain more insight into
      interindividual differences in this ability. METHOD: Using an adaptive procedure
      similar to the SRT test, the TRT test determines the percentage of unmasked text
      needed to read 50% of sentences correctly. SRTs in stationary noise (SRT(STAT)),
      modulated noise (SRT(MOD)), and TRTs were determined for 34 participants with
      normal hearing, aged 19 to 78 years. RESULTS: The results indicate that about 30%
      of the variance in SRT(STAT) and SRT(MOD) is shared with variance in TRT, which
      reflects the shared involvement of a modality-aspecific cognitive or linguistic
      ability in forming meaningful wholes of fragments of sentences. CONCLUSION: The
      TRT test, a visual analogue of the SRT test, has been developed to measure the
      variance in speech-in-noise comprehension associated with modality-aspecific
      cognitive skills. In future research, normative data of the TRT test should be
      developed. It would also be interesting to measure TRTs of individuals
      experiencing difficulties understanding speech.

PMID- 17538102
TI  - Delayed initiation of the pharyngeal swallow: normal variability in adult
      swallows.
AB  - PURPOSE: The purpose of this investigation was to determine bolus head timing and
      location relations with the onset of hyoid movement at the initiation of the
      pharyngeal swallow and at the onset of swallow-related apnea. METHOD: Bolus head
      timing and location and the timing of swallow-related apnea were recorded from
      frame-by-frame analyses of 5-ml single liquid swallows using dual-modality
      videofluoroscopy and nasal airflow recordings in 82 consecutive, healthy
      volunteers. The presence, depth, and response to airway entry were also recorded
      and related to the bolus head location and the onset of hyoid movement. RESULTS:
      The majority of participants-80% on at least 1 trial-produced the onset of hyoid
      movement at pharyngeal swallow initiation after the bolus head passed the
      posterior angle of the mandible. There was a trend in older participants for
      later onset of hyoid movement and onset of apnea relative to bolus head arrival
      at the posterior angle of the mandible. CONCLUSION: Although entry of the bolus
      head into the pharynx prior to hyoid movement may result in a threat to the
      laryngeal airway, these data demonstrate that a "delay" by itself cannot be
      assumed to indicate a disordered swallow without coexisting impairments of
      swallowing physiology.

PMID- 17538103
TI  - Measures of the glottal source spectrum.
AB  - PURPOSE: Many researchers have studied the acoustics, physiology, and perceptual
      characteristics of the voice source, but despite significant attention, it
      remains unclear which aspects of the source should be quantified and how
      measurements should be made. In this study, the authors examined the
      relationships among a number of existing measures of the glottal source spectrum,
      along with the association of these measures to overall spectral shapes and to
      glottal pulse shapes, to determine which measures of the source best capture
      information about the shapes of glottal pulses and glottal source spectra.
      METHOD: Seventy-eight different measures of source spectral shapes were made on
      the voices of 70 speakers. Principal components analysis was applied to
      measurement data, and the resulting factors were compared with factors similarly
      derived from oral speech spectra and glottal pulses. RESULTS: Results revealed
      high levels of duplication and overlap among existing measures of source spectral
      slope. Further, existing measures were not well aligned with patterns of spectral
      variability. In particular, existing spectral measures do not appear to model the
      higher frequency parts of the source spectrum adequately. CONCLUSION: The failure
      of existing measures to adequately quantify spectral variability may explain why
      results of studies examining the perceptual importance of spectral slope have not
      produced consistent results. Because variability in the speech signal is often
      perceptually salient, these results suggest that most existing measures of source
      spectral slope are unlikely to be good predictors of voice quality.

PMID- 17538104
TI  - Determination of phonation instability pressure and phonation pressure range in
      excised larynges.
AB  - PURPOSE: The present study was a methodological study designed to reveal the
      dynamic mechanisms of phonation instability pressure (PIP) using bifurcation
      analysis. Phonation pressure range (PPR) was also proposed for assessing the
      pressure range of normal vocal fold vibrations. METHOD: The authors first
      introduced the concept of bifurcation on the basis of a symmetric vocal fold
      model and then applied the bifurcation analysis to data from excised larynges. By
      recording acoustic signals from 10 excised larynges, the authors measured
      phonation threshold pressure (PTP), PIP, and PPR at the bifurcation pressure
      points from the spectrograms as subglottal pressure was progressively increased.
      Furthermore, to investigate the effects of vocal fold elongation on PTP, PIP, and
      PPR, the authors manipulated the elongation of the vocal folds at 0%, 5%, 10%,
      and 15% of the resting vocal fold length. RESULTS: The authors found that PTP,
      PIP, and PPR were effectively determined using the bifurcation analysis. When
      vocal fold elongation was increased from 0% to 15%, PTP was significantly
      increased (p < .001), PIP was not significantly changed (p = .54), and PPR was
      significantly decreased (p = .003). CONCLUSION: PIP and PPR represent important
      parameters to assess phonation instability. Bifurcation analysis represents a
      valuable procedure for revealing the mechanisms behind PTP, PIP, and PPR and for
      investigating the effects of vocal fold biomechanical parameters on these 3
      pressure parameters.

PMID- 17538105
TI  - Effect of cues to increase sound pressure level on respiratory kinematic patterns
      during connected speech.
AB  - PURPOSE: This study examined the response of the respiratory system to 3 cues
      used to elicit increased vocal loudness to determine whether the effects of
      cueing, shown previously in sentence tasks, were present in connected speech
      tasks and to describe differences among tasks. METHOD: Fifteen young men and 15
      young women produced a 2-paragraph reading passage in response to 4 different
      loudness cues: comfortable loudness level, targeting 10 dB above comfortable, at
      what they perceived as twice their comfortable loudness, and with multitalker
      noise present in the background. A short monologue was produced at comfortable
      loudness level and with noise in the background. RESULTS: Differences in
      respiratory strategies were demonstrated for the different cueing conditions,
      similar to patterns observed in sentence productions. The kinematic patterns were
      similar for reading and monologue; however, utterances were longer and speaking
      rate was slower in the monologue task. CONCLUSION: The findings extend the
      results from sentences to connected speech and provide support for the hypothesis
      that "intention" or goals play a role in the control of respiratory function
      during speech. Respiratory kinematics were similar across tasks, when the same
      cue was used, except for differences related to breath group length and speech
      rate.

PMID- 17538106
TI  - The effects of three nebulized osmotic agents in the dry larynx.
AB  - PURPOSE: This investigation examined the effects of nebulized hypertonic saline,
      isotonic saline (IS), and sterile (hypotonic) water on phonation threshold
      pressure (PTP) and self-perceived phonatory effort (PPE) following a surface
      laryngeal dehydration challenge. METHOD: In a double-blind, randomized
      experimental trial, 60 vocally healthy women (n = 15 per group) underwent a
      laryngeal desiccation challenge involving oral breathing for 15 min using medical
      grade dry air (RH<1%). Three of the four groups then received nebulized isotonic
      saline (0.9% NaCl), hypertonic saline (7% NaCl), or sterile (hypotonic) water,
      respectively; the 4th group served as a nontreatment control. PTP and PPE were
      estimated for high-pitched productions at baseline, immediately postdesiccation,
      and at 5, 20, 35, and 50 min postnebulization. RESULTS: PTP increased
      significantly for all groups following the desiccation challenge. PTP values
      were, on average, 0.5 cm H(2)O greater immediately postdesiccation versus
      baseline. In contrast, PTP values did not change significantly following the
      administration of nebulized treatments, although a temporary trend toward a
      reduction in PTP was observed for the IS group. Unexpectedly, PPE ratings
      decreased significantly after the desiccation challenge. In general, PPE ratings
      were poorly correlated with PTP measures. CONCLUSION: A laryngeal desiccation
      challenge (i.e., temporary exposure to extremely low relative humidity while
      breathing transorally) significantly increased PTP. Although interesting trends
      emerged, none of the nebulized treatments significantly enhanced recovery from
      the negative effects of desiccation on PTP. In light of very low correlations
      between PTP and PPE, serious questions are raised regarding presumed associations
      between these measures.

PMID- 17538107
TI  - Basic auditory processing skills and specific language impairment: a new look at
      an old hypothesis.
AB  - PURPOSE: To explore the sensitivity of children with specific language impairment
      (SLI) to amplitude-modulated and durational cues that are important for
      perceiving suprasegmental speech rhythm and stress patterns. METHOD: Sixty-three
      children between 7 and 11 years of age were tested, 21 of whom had a diagnosis of
      SLI, 21 of whom were matched for chronological age to the SLI sample, and 21 of
      whom were matched for language age to the SLI sample. All children received a
      battery of nonspeech auditory processing tasks along with standardized measures
      of phonology and language. RESULTS: As many as 70%-80% of children diagnosed with
      SLI were found to perform below the 5th percentile of age-matched controls in
      auditory processing tasks measuring sensitivity to amplitude envelope rise time
      and sound duration. Furthermore, individual differences in sensitivity to these
      cues predicted unique variance in language and literacy attainment, even when
      age, nonverbal IQ, and task-related (attentional) factors were controlled.
      CONCLUSION: Many children with SLI have auditory processing difficulties, but for
      most children, these are not specific to brief, rapidly successive acoustic cues.
      Instead, sensitivity to durational and amplitude envelope cues appear to predict
      language and literacy outcomes more strongly. This finding now requires
      replication and exploration in languages other than English.

PMID- 17538108
TI  - Predicting outcomes of children referred for autism using the MacArthur-Bates
      Communicative Development Inventory.
AB  - PURPOSE: Autism spectrum disorders (ASD) are characterized by early impairments
      in language and related social communication skills. This investigation explored
      whether scores on the MacArthur-Bates Communicative Development Inventory (CDI)
      at ages 2 and 3 years predict outcome at age 9 years in children with ASD and
      developmental delay (DD). METHOD: Sixty-two children referred for possible autism
      at age 2 years, and 19 children with DD, were followed to age 9 years.
      Vocabulary, prespeech, and gestures scores on CDIs administered at ages 2 and 3
      years were used to predict follow-up IQ, language, adaptive skills, and scores on
      diagnostic measures. RESULTS: CDI scores at ages 2 and 3 did not predict outcome
      for the DD group. For the ASD sample, CDI receptive and expressive language and
      late gestures at ages 2 and 3 years predicted a number of follow-up variables,
      although scores at age 3 years were generally more predictive than scores at age
      2 years. CONCLUSIONS: The CDI yielded scores that were predictive of outcome,
      suggesting that this parent report measure may be a quick and informative
      assessment of early verbal and nonverbal skills in children with ASD.

PMID- 17538109
TI  - Fast mapping skills in the developing lexicon.
AB  - PURPOSE: This preliminary investigation was a longitudinal study of fast mapping
      skills in normally developing children, 16-18 months of age. The purpose was to
      examine the effects of practice on the accessibility of words in lexical memory.
      METHOD: Eight children were taught the names of 24 unfamiliar objects over 12
      weekly training sessions. The amount of practice children had with individual
      words varied as a function of session. Data were compared to a control group of
      children-matched on productive vocabulary-who were exposed to the same
      experimental words at the first and last sessions only. RESULTS: The results
      showed that for children in the experimental group, extended practice with a
      novel set of high-practice words led to the rapid acquisition of a second set of
      low-practice words. Children in the control group did not show the same lexical
      advantage. CONCLUSIONS: The data suggest that learning some words primes the
      system to learn more words. Vocabulary development can thus be conceptualized as
      a continual process of fine-tuning the lexical system to enable increased
      accessibility to information. Implications for the treatment of children with
      word-finding difficulties are considered.

PMID- 17538110
TI  - Specific language impairment in French-speaking children: beyond grammatical
      morphology.
AB  - PURPOSE: Studies on specific language impairment (SLI) in French have identified
      specific aspects of morphosyntax as particularly vulnerable. However, a cohesive
      picture of relative strengths and weaknesses characterizing SLI in French has not
      been established. In light of normative data showing low morphological error
      rates in the spontaneous language of French-speaking preschoolers, the relative
      prominence of such errors in SLI in young children was questioned. METHOD:
      Spontaneous language samples were collected from 12 French-speaking preschool-age
      children with SLI, as well as 12 children with normal language development
      matched on age and 12 children with normal language development matched on mean
      length of utterance. Language samples were analyzed for length of utterance;
      lexical diversity and composition; diversity of grammatical morphology and
      morphological errors, including verb finiteness; subject omission; and object
      clitics. RESULTS: Children with SLI scored lower than age-matched children on all
      of these measures but similarly to the mean length of utterance-matched controls.
      Errors in grammatical morphology were very infrequent in all groups, with no
      significant group differences. CONCLUSION: The results indicate that the
      spontaneous language of French-speaking children with SLI in the preschool age
      range is characterized primarily by a generalized language impairment and that
      morphological deficits do not stand out as an area of particular vulnerability,
      in contrast with the pattern found in English for this age group.

PMID- 17538111
TI  - The influence of semantic processing on phonological decisions in children and
      adults: a magnetoencephalography (MEG) study.
AB  - PURPOSE: To examine the behavioral effects and neural activation patterns
      associated with implicit semantic processing influences on phonological judgments
      during reading in children and adults. METHOD: Whole-head magnetoencephalography
      (MEG) recordings were obtained from 2 groups, children (9-13 years) and adults,
      performing a homophone judgment task. The stimuli consisted of pairs of
      sequentially presented written words that were either homophones, synonym foils,
      or unrelated control words. RESULTS: The difference in the time taken to respond
      to synonym pairs relative to control pairs of stimuli, called the semantic
      interference effect (SIE), was, on average, 24 ms for adults and 86 ms for
      children. Source analysis of the MEG data using minimum-norm estimation (MNE)
      yielded less activation in the adults for the synonym condition compared with the
      control condition in right anterior temporal and inferior frontal cortex 300-500
      ms after the onset of the 2nd word in a pair, suggestive of semantic priming as
      well as inhibition of the SIE. A similar priming effect was observed for the
      children in left-anterior temporal cortex. CONCLUSION: The observed group
      differences in the magnitude of the SIE and brain activation patterns may reflect
      developmental differences in the effects of semantic information on phonological
      decisions during word processing.

PMID- 17538112
TI  - Tapping toddlers' evolving semantic representation via gesture.
AB  - PURPOSE: This study presents evidence that gesture is a means to understanding
      the semantic representations of toddlers. METHOD: The data were part of a study
      of toddlers' word learning conducted by N. C. Capone and K. K. McGregor (2005).
      The object function probe from that study was administered after 1 exposure and
      after 3 exposures to objects. Here, toddlers' gestures were described and their
      gesture-speech combinations were analyzed as a function of instruction and time.
      RESULTS: A large proportion of toddlers gestured. Gestures were iconic and
      deictic, but toddlers produced more iconic gestures than previously reported.
      Consistent with studies of older children, toddlers produced gesture-speech
      combinations that reflected their learning state. CONCLUSION: Gesture can be both
      a source of semantic knowledge and an expression of that knowledge. Gesture
      provides a window onto evolving semantic representations and, therefore, can be 1
      method of assessing what a child knows at a time when oral language skills are
      limited and are, perhaps, an unreliable indicator of what the child knows.
      Embodied knowledge may underlie the use of gesture. Clinical implications are
      discussed.

PMID- 17538113
TI  - Do children and adults with language impairment recognize prosodic cues?
AB  - PURPOSE: Prosodic cues are used to clarify sentence structure and meaning. Two
      studies, one of children with specific language impairment (SLI) and one of
      adults with a history of learning disabilities, were designed to determine
      whether individuals with poor language skills recognize prosodic cues on par with
      their normal-language peers. METHOD: Participants were asked to determine whether
      low-pass filtered sentences matched unfiltered target sentences. Filtered
      sentences either matched the target sentence exactly or differed on between 1 and
      3 parameters that affected the prosodic profile of the sentences. RESULTS:
      Children with SLI were significantly poorer than their normal peers in
      determining whether low-pass filtered sentences matched or were different from
      unfiltered target sentences. The children's performance, measured in terms of
      response accuracy, deteriorated as the similarities between filtered and
      unfiltered sentences increased. Adults revealed a pattern of differential
      reaction time to sentence pairs that reflected their relative degree of
      similarity. There was no difference in performance accuracy for adults with a
      history of language/learning disabilities compared with their peers. CONCLUSION:
      Given that prosodic cues are known to assist language processing, the weak
      prosodic skills of preschool children with SLI may limit the amount of benefit
      that these children derive from the presence of prosodic cues in spoken language.
      That the adult sample did not show a similar weakness in this skill may reflect
      developmental differences, sampling differences, or a combination of both.

PMID- 17538114
TI  - Lexical aspect and the use of verb morphology by children with specific language
      impairment.
AB  - PURPOSE: Many typically developing children first use inflections such as -ed
      with verb predicates whose meanings are compatible with the functions of the
      inflection (e.g., using -ed when describing events of brief duration with clear
      end points, such as dropped). This tendency is assumed to be beneficial for
      development. In this study, the authors examine whether preschool-aged children
      with specific language impairment (SLI) show a similar tendency. METHOD: Sixteen
      children in each of three groups participated-children with SLI, typically
      developing children matched for age (TD-A), and younger typically developing
      children matched for mean length of utterance (TD-MLU). The children described
      actions in contexts that promoted either past tense -ed or progressive aspect 
      ing in past contexts. Half of the verb predicates referred to events of brief
      duration with distinct endpoints (e.g., drop), and half referred to events of
      considerable duration with less distinct points of termination (e.g., play).
      RESULTS: Both the TD-A children and the TD-MLU children used -ed with verb
      predicates of the first type more consistently than they did with verb predicates
      of the second type. They showed the reverse pattern for -ing. The children with
      SLI did not show any effects according to the verb predicate type. However,
      although the children with SLI made less overall use of -ed than did both groups
      of TD children, they differed only from the TD-A children in their overall use of
      -ing. CONCLUSION: Difficulties with tense-related morphology may be compounded in
      children with SLI if they fail to make use of associations between the lexical
      aspect of verb predicates and the grammatical function of the accompanying
      inflections. The authors argue that the advantages of using these associations as
      a starting point in acquisition may be especially important in the case of -ed.
      Additional studies of children with SLI are clearly needed, including those that
      employ longitudinal, naturalistic data.

PMID- 17538115
TI  - Examining the language performances of children with and without specific
      language impairment: contributions of phonological short-term memory and speed of
      processing.
AB  - PURPOSE: This study investigated the effects of processing speed and phonological
      short-term memory (PSTM) on children's language performance. METHOD: Forty-eight
      school-age children with specific language impairment (SLI) and age peers
      completed auditory detection reaction time (RT) and nonword repetition tasks, the
      Clinical Evaluation of Language Fundamentals-Revised (CELF-R; E. Semel, E. Wiig,
      & W. Secord, 1987), and a word recognition RT task. Correlation and regression
      were used to determine unique and shared contributions to variance among
      measures. RESULTS: Children with SLI were outperformed by age peers on each task.
      Auditory detection RT was correlated with nonword repetition (NWR) in each group.
      However, both variables covaried with age, and auditory detection RT did not
      contribute unique variance to NWR in either group. For the SLI group, NWR
      predicted unique variance in CELF-R performance (about 15%); auditory detection
      RT predicted a smaller amount of unique variance in the word recognition RT task
      (about 9%). CONCLUSION: Processing speed and PSTM measures covaried with
      chronological age. Processing speed was associated with offline language
      performance only through association with PSTM. Processing speed contributed to
      online language performance, suggesting that speed is associated with processing
      more familiar language material (i.e., lexical content and structure) than less
      familiar material (e.g., various content on the CELF-R).

PMID- 17538116
TI  - What should chris say? The ability of children with specific language impairment
      to recognize the need to dissemble emotions in social situations.
AB  - PURPOSE: In this study, the authors examined the ability of children with
      specific language impairment (SLI) and their typical peers to judge when an
      experienced emotion should be dissembled (hidden) in accord with social display
      rules. METHOD: Participants included 19 children with SLI and19 children with
      typical language skills, both groups ranging in age from 7;9 (years;months) to
      10;10, with a mean age of 9;1. Children were presented with 10 hypothetical
      social situations in which a character, Chris, experienced an emotion that should
      be dissembled for social purposes. The participants' responses were categorized
      as to whether or not they dissembled or displayed the emotion. RESULTS: Although
      the task was difficult for many participants, children with SLI indicated that
      the experienced emotion should be dissembled significantly less often than did
      their typical peers. Children in the 2 groups did not significantly differ in
      their judgments of the social display rules governing these situations.
      CONCLUSION: These results suggested that the children with SLI did not understand
      the impact of displaying emotion on relationships in the same way as did their
      typical peers. In this respect, they seemed to lag behind the typical children in
      their developing emotion knowledge.

PMID- 17538117
TI  - Parasite-induced chronic inflammation is not exacerbated by immunotherapy before
      or during Trypanosoma cruzi Infection.
AB  - Trypanosoma cruzi infection causes Chagas' disease, a chronic inflammatory
      disease. The specific inflammatory responses that cause Chagas' disease remain
      unclear, but data argue that parasites that persist in the host stimulate chronic
      self-damaging immune responses. Because T. cruzi appears to stimulate self
      damaging responses, the enthusiasm to develop vaccines that boost antiparasite
      responses that might increase self-damaging responses has been limited. We
      previously demonstrated that immunization with a T. cruzi trans-sialidase protein
      or adoptive transfer of trans-sialidase-specific T-cell clones decreased
      parasitemia, morbidity, and mortality. Here we report that immunization or
      adoptive transfer with the protein or clones, before or during T. cruzi
      infection, boosts the anti-T. cruzi immune response without exacerbating acute or
      chronic tissue inflammation. These results argue that prophylactic and
      therapeutic immunotherapy for Chagas' disease can be developed safely.

PMID- 17538118
TI  - Human polyomavirus type 1 (BK virus) agnoprotein is abundantly expressed but
      immunologically ignored.
AB  - Impaired BK virus (BKV)-specific immunity is a key risk factor of polyomavirus
      associated nephropathy. We hypothesized that BKV agnoprotein might constitute an
      important immune target, as it is highly expressed after infection in vitro. We
      demonstrate abundant expression of BKV agnoprotein in vivo by immunostaining of
      kidney transplant (KT) biopsy specimens. Antibody responses to the recombinant
      affinity-purified BKV agnoprotein, large tumor (LT), and VP1 antigens in 146 sera
      from 38 KT patients and in 19 sera from 16 healthy donors (HD) were compared by
      enzyme immunoassay. In HD, low titers of anti-agnoprotein immunoglobulin G (IgG)
      were found in 15% of sera, compared to 41% for anti-LT antigen and 63% for anti
      VP1. No anti-BKV IgM was detectable. In KT patients, anti-agnoprotein IgG and IgM
      were found in 8% and 3.6% of sera, compared to 63% and 18% for anti-LT IgG and
      IgM and 80% and 41% for anti-VP1 IgG and IgM, respectively. Anti-LT antigen and
      anti-VP1, but not anti-agnoprotein, activities increased during and after BKV
      viremia in KT patients. To investigate specific cellular immune responses, we
      compared levels of gamma interferon production in peripheral blood mononuclear
      cells (PBMC) of 10 HD and 30 KT patients by enzyme-linked immunospot assay. In
      HD, the median numbers of gamma interferon spot-forming units per million PBMC
      for the agnoprotein, LT antigen, and VP1 peptides were 1, 23, and 25,
      respectively, whereas the responses in KT patients were 2, 24, and 99,
      respectively. We conclude that BKV agnoprotein, though abundantly expressed in
      vivo, is poorly recognized immunologically.

PMID- 17538119
TI  - Quantification of 1,3-beta-D-glucan levels in children: preliminary data for
      diagnostic use of the beta-glucan assay in a pediatric setting.
AB  - 1,3-Beta-D-Glucan serum levels have demonstrated good diagnostic sensitivity and
      specificity for the diagnosis of candidiasis in adult patients, but normal levels
      for children have not been established. We found higher 1,3-beta-D-glucan levels
      in children than those previously reported in adults.

PMID- 17538120
TI  - Gene expression changes in peripheral blood mononuclear cells during measles
      virus infection.
AB  - Measles virus continues to cause morbidity and mortality despite the existence of
      a safe and efficacious vaccine. Measles is associated with induction of both a
      long-lived protective immune response and immunosuppression. To gain insight into
      immunological changes during measles virus infection, we examined gene expression
      in blood mononuclear cells from children with acute measles and children in the
      convalescent phase compared to uninfected control children. There were 13
      significantly upregulated and 206 downregulated genes. Upregulated genes included
      the immune regulatory molecules interleukin 1beta (IL-1beta), CIAS-1, tumor
      necrosis factor alpha, PDE4B, PTGS2, IL-8, CXCL2, CCL4, ICAM-1, CD83, GOS-2, IER3
      (IEX-1), and TNFAIP3 (A20). Plasma levels of IL-1beta and IL-8 were elevated
      during measles virus infection. Downregulated genes mainly involved three gene
      ontology biological processes, transcription, signal transduction, and the immune
      response, and included IL-16 and cell surface receptors IL-4R, IL-6R, IL-7R, IL
      27RA, CCR2, and CCR7. Most mRNAs had not returned to control values 1 month after
      discharge, consistent with prolonged immune response abnormalities during measles
      virus infection.

PMID- 17538121
TI  - Identification of a novel immunosubversion mechanism mediated by a virologue of
      the B-lymphocyte receptor TACI.
AB  - TACI (transmembrane activator and calcium modulator and cyclophilin ligand [CAML]
      interactor) is a part of a novel network of ligands and receptors involved in B
      cell survival and isotype switching. The TACI protein mediates its effects
      through CAML, an endoplasmic reticulum (ER)-localized protein that controls
      Ca(2+) efflux. The adenovirus E3-6.7K protein prevents inflammatory responses and
      also confers resistance from a variety of apoptotic stimuli and maintains ER
      Ca(2+) homeostasis; however, the mechanism of action is unknown. Here, we provide
      evidence that E3-6.7K shares sequence homology with TACI and inhibits apoptosis
      and ER Ca(2+) efflux through an interaction with CAML, a Ca(2+)-modulating
      protein. We demonstrate a direct interaction between E3-6.7K and CAML and reveal
      that the two proteins colocalize in an ER-like compartment. Furthermore, the
      interaction between the two proteins is localized to the N-terminal domain of
      CAML and to a 22-amino-acid region near the C terminus of E3-6.7K termed the CAML
      binding domain (CBD). Mutational analysis of the CBD showed that an interaction
      with CAML is required for E3-6.7K to inhibit thapsigargin-induced apoptosis and
      ER Ca(2+) efflux. E3-6.7K appears to be the first virologue of TACI to be
      identified. It targets CAML in a novel immunosubversive mechanism to alter ER
      Ca(2+) homeostasis, which consequently inhibits inflammation and protects
      infected cells from apoptosis.

PMID- 17538122
TI  - Epitope length, genospecies dependency, and serum panel effect in the IR6 enzyme
      linked immunosorbent assay for detection of antibodies to Borrelia burgdorferi.
AB  - In the absence of erythema migrans, the basis for diagnosis of Lyme disease is
      the demonstration of an antibody response against Borrelia burgdorferi in an
      appropriate clinical setting. The C6 enzyme-linked immunosorbent assay, based on
      the IR6 region of VlsE, has become widely used in both the United States and
      Europe. We mapped the antigenic epitopes of IR6 to a shorter sequence that is
      equivalent in sensitivity and specificity to the full-length IR6 25-residue
      peptide. In addition, we observed significant differences in sensitivity between
      serum panels (60 to 100%), indicating that the selection of the serum panels can
      shape the apparent overall sensitivity of the assay. Contrary to prior reports,
      the assay sensitivity is greater when the IR6 peptide is derived from the
      sequence of the same infecting Borrelia genospecies. Using our North American
      panels and the two panels obtained from European Lyme disease patients, we
      determined that the IR6 assay that is based on a single genospecies of Borrelia
      spp. is not optimal for use as a universal diagnostic assay for Lyme disease.

PMID- 17538123
TI  - Checkmate: a primer on overcoming the complex challenges inherent in pediatric
      nursing research.

PMID- 17538124
TI  - Testing the acceptance of asthma model with children and adolescents.
AB  - Older school-age children and early adolescents with asthma have demonstrated and
      verbalized difficulty in accepting their condition. Although researchers have
      explored adult acceptance, few have explored child or adolescent acceptance. The
      purpose was to explore the fit of the data to a specified latent variable
      acceptance of asthma model. School-age children and early adolescents (N = 118),
      ages 9 to 14 years enrolled in Grades 4 to 9, diagnosed with asthma and their
      parents completed self-report instruments. EQS was used for structural equation
      modeling analyses. The specified model was a good fit to the data and accounted
      for more than 70% in the explained variance of vigilance, 30% of participation in
      life activities, 25% of taking control, and 20% of asthma health behaviors.
      Support for the model possess implications for development of theory-based
      education and counseling interventions to support participation in life
      activities by targeting cognitive, behavioral, and psychosocial aspects of living
      with the asthma.

PMID- 17538125
TI  - The difficulties of studying children's pain at home.
AB  - Children experience moderate to severe pain in the days after tonsillectomy
      surgery. This article describes the challenges of analyzing data from pain
      diaries 24 hours after ambulatory tonsillectomy surgery. Instructions were to
      record pain levels every 4 hours and the analgesic as given; however, the number
      of entries was inconsistent, making comparison of groups difficult. The use of
      analgesics can threaten the construct validity of cause and must be considered
      and controlled statistically. Opioids were converted to morphine equivalents and
      the nonopioids were held as a separate covariate. This article describes the
      steps taken to find an appropriate statistical means of dealing with inconsistent
      diary entries and analgesic use. Hierarchical linear modeling (HLM) provides a
      means to analyze unbalanced data and control for analgesics. Issues of control
      must be addressed in research that measures children's pain in the home. HLM can
      address issues of incomplete data in repeated-measures studies.

PMID- 17538126
TI  - Conducting end-of-life studies in pediatric oncology.
AB  - Improving our ability to prevent or diminish suffering in dying children and
      adolescents and their families is dependent on the completion of high-quality
      pediatric end-of-life studies. The purpose of this article is to provide useful
      evidence-based strategies that have been used to implement and complete
      clinically useful pediatric end-of-life studies in oncology. The article
      describes specific peer-review and methodological challenges and links those to
      evidence-based solutions. The challenges and solutions described in this article
      are from eight end-of-life studies involving pediatric oncology patients. It is
      hoped that the solutions described here will benefit others in their efforts to
      implement pediatric end-of-life studies so that clinically useful findings will
      result and will improve the care of dying children and adolescents.

PMID- 17538127
TI  - Assent of school-age bilingual children.
AB  - This article discusses the issue of assent of school-age bilingual children to
      participate in a research study. The article reviews cognitive, cultural, and
      linguistic factors influencing verbal and nonverbal concept formation in
      bilingual children. At the applied level, the focus of the article is on
      methodological considerations in using this information to obtain assent from a
      child who is bilingual and speaks English as a second language. Recommendations
      for the assessment of the child's language dominance, language proficiency, and
      the development of the assent form are provided. Language diversity and its
      potential effects on the assent process need to be formally acknowledged and
      appropriately addressed.

PMID- 17538128
TI  - Barriers and strategies for recruiting study participants in clinical settings.
AB  - Recruiting participants for research studies is often a challenging task.
      Recruitment requires careful planning, collaboration, and flexibility on the part
      of researchers and health care providers at the recruitment sites. This article
      describes six major barriers to recruiting study participants as identified from
      a review of the literature and from the coauthors' research experiences. These
      barriers include challenges related to regulations of the Health Insurance
      Portabililty and Accountability Act (HIPAA), health care providers' work burden,
      providers' financial disincentives, competition, health care provider concerns
      regarding research, and provider protection of patients. Each barrier is
      described, and specific strategies are suggested based on the empirical
      literature. In some instances, the coauthors' experiences are also shared.

PMID- 17538129
TI  - Accessing and recruiting children for research in schools.
AB  - Gaining access to the schools and recruiting children as research participants
      are challenging tasks. To facilitate gaining access to the schools, multiple
      strategies are necessary, including understanding specific characteristics of the
      schools, using the proper lines of authority and communication, identifying the
      gatekeepers, and persuading the schools of the significance and mutual benefits
      from the study. Once access is gained, strategies for successful recruitment of
      children include use of developmentally appropriate motivators and incentives;
      multilevel communications with administrators, principals, teachers, staff,
      parents/guardians, and children; and provision of privacy and confidentiality
      during data collection and sharing of the findings. Specific examples from an
      ongoing study are used to illustrate helpful strategies.

PMID- 17538130
TI  - Infections related to coils used for embolization of arteries: review of the
      published evidence.
AB  - The embolization of arteries with the use of coils has been an advance in the
      management of patients such as those at risk for aneurysm rupture. However, this
      procedure is not without complications. A systematic review was undertaken to
      evaluate the available evidence regarding infectious complications directly
      related to endovascular coil embolization. Seven case reports of patients who
      experienced infection related to coils used for embolization of arteries were
      discovered. Arteries embolized with coils in these patients were intracranial,
      intraabdominal, and intrathoracic, respectively, in four, two, and one case.
      Abscess formation in the area of coil placement (n = 6; 85.7%) was the most
      common infectious complication directly related to endovascular coil
      embolization. Staphylococcus aureus was the predominant isolated pathogen (n = 3;
      42.9%). Other isolated pathogens included Salmonella species type D (n = 1;
      14.3%), S. epidermidis (n = 1; 14.3%), Escherichia coli (n = 1; 14.3%), and
      Bacteroides fragilis (n = 1; 14.3%). Surgical procedures were performed in four
      of the seven patients described (57.1%), and three patients were treated with
      only the administration of antimicrobial agents. All reviewed patients were
      cured. Even though it may partially be a result of reporting bias, the scarcity
      of reports describing infections directly related to endovascular coils despite
      the increasing number of patients who received this treatment in various parts of
      the world suggests that infectious complications associated with this foreign
      endovascular material are very rare. However, the existence of the identified
      case reports suggests that clinicians should include coil-related infection in
      the differential diagnosis of patients with fever after this procedure.

PMID- 17538131
TI  - Initial clinical experience with the 4-F self-expanding XPERT stent system for
      infrapopliteal treatment of patients with severe claudication and critical limb
      ischemia.
AB  - PURPOSE: To evaluate the primary success and short-term patency associated with a
      new 4-F sheath-compatible self-expanding nitinol stent after failed conventional
      angioplasty of distal popliteal and infrapopliteal lesions in severe lifestyle
      limiting claudication (LLC) and chronic critical limb ischemia (CLI). MATERIALS
      AND METHODS: Between May 2003 and July 2005, 35 patients with Rutherford category
      3-5 disease (16 patients with CLI, 19 patients with LLC) underwent percutaneous
      transluminal angioplasty (PTA) and stent implantation. Indications for stent
      placement were residual stenosis, flow-limiting dissections, or elastic recoil
      after PTA. Before and after the intervention and during the 6-month follow-up,
      clinical investigation, color-flow and duplex Doppler ultrasonography, and
      digital subtraction angiography were performed. Technical success, primary
      patency at 6 months, clinical improvement as defined by Rutherford with clinical
      and hemodynamic measures, and complications were evaluated. RESULTS: A total of
      22 patients underwent distal popliteal artery stent placement and 13 underwent
      tibioperoneal artery stent placement. Stent implantation was successfully
      performed in all patients. After stent placement, the primary cumulative patency
      rate for the study group at 6 months was 82%. The mean resting ankle-brachial
      index at baseline was 0.50 +/- 0.16 and significantly increased to 0.90 +/- 0.17
      at 12-24 hours after intervention and 0.82 +/- 0.24 at latest follow-up (P < .001
      for both). The sustained clinical improvement rate was 80% at the 6-month follow
      up. The 6-month limb salvage rate regarding major amputation was 100%. The rate
      of major complications was 17%. CONCLUSIONS: Infrapopliteal application of the
      new nitinol stent is a safe, feasible, and effective method with good short-term
      patency rate in the treatment of severe LLC and chronic CLI.

PMID- 17538132
TI  - Ultrahigh-pressure versus high-pressure angioplasty for treatment of venous
      anastomotic stenosis in hemodialysis grafts: is there a difference in patency?
AB  - PURPOSE: Ultrahigh-pressure (UHP) balloon catheters were compared with high
      pressure (HP) balloon catheters to determine if there was a difference in patency
      after percutaneous transluminal angioplasty (PTA) of venous anastomotic stenoses.
      MATERIALS AND METHODS: A retrospective study was conducted from January 2001 to
      September 2005 that included 22 patients with synthetic hemodialysis grafts who
      underwent 110 PTA procedures for venous anastomotic stenoses. Data collected
      included graft configuration and location, percent stenosis, balloon type used,
      residual stenosis, and total access blood flow before and after intervention.
      Patency from time of initial PTA to the next intervention was estimated with the
      Kaplan-Meier technique, with initial failures included in the analysis. RESULTS:
      A total of 55 PTAs were performed in each group. Technical success rate was 96%
      (n = 106) and clinical success rate was 100%. Median survival times were 4.6
      months for the UHP cohort and 5.4 months for the HP group. When each event was
      considered independent, the difference was significant (P = .014). However, when
      each PTA event was considered dependent on earlier PTA events, no significant
      difference in patency was observed (P = .64). The mean increases in access blood
      flow rate by ultrasound dilution (available for 71 events) after PTA were 264
      mL/min with UHP and 524 mL/min with HP (P = .14, Student t test). One minor
      complication (0.9%) of focal extravasation after PTA occurred and resolved with
      prolonged balloon inflation. CONCLUSION: Routine use of UHP for PTA of venous
      anastomotic stenoses in synthetic hemodialysis grafts was not associated with any
      significant change in patency compared with routine HP balloon angioplasty.

PMID- 17538133
TI  - Pharmacomechanical thrombectomy of acute deep vein thrombosis with the Trellis-8
      isolated thrombolysis catheter.
AB  - PURPOSE: To evaluate the performance of the Trellis-8 isolated thrombolysis
      catheter during single-session pharmacomechanical thrombectomy (PMT) combined
      with low-dose thrombolysis with tissue plasminogen activator (TPA) in the
      treatment of patients with acute deep vein thrombosis (DVT) and multiple
      comorbidities. MATERIALS AND METHODS: Retrospective analysis was performed of 19
      consecutive patients with acute above-knee DVT treated by PMT with the Trellis
      device followed by venous angioplasty and stent placement. Isolated thrombolysis
      with low-dose TPA was used with all patients. Concurrent therapies included
      retrievable inferior vena cava filter insertion (n = 4). The primary endpoint was
      restoration of rapid inline venous flow; the secondary endpoint was thrombus
      clearance. RESULTS: Restoration of rapid inline venous flow was achieved in all
      cases; thrombus removal was less than 50% in one case (4%), 50%-95% in 18 cases
      (82%), and at least 95% in three cases (14%). The median administered dose of TPA
      was 13.4 mg per patient. The mean treatment time was 91 minutes per limb (range,
      61-129 min), with a mean of 21 minutes per thrombosed segment (range, 8-31 min).
      There were no major complications. Primary patency rate of the treated venous
      segments at 2 days was 86% (n = 19) and the primary assisted patency rate was
      100% at 30 days. Two patients died of advanced malignancy at 17 and 24 days.
      CONCLUSIONS: The Trellis system was an effective method for the treatment of
      acute DVT. Based on the present data, the Trellis system could prove to be a safe
      and feasible single-session PMT method for the treatment of acute DVT in a
      broader patient population and warrants further investigation in a large-scale
      study.

PMID- 17538134
TI  - Fate of migrated esophageal and gastroduodenal stents: experience in 70 patients.
AB  - PURPOSE: To investigate the frequency of esophageal and gastroduodenal stent
      migration and the fate of such stents. MATERIALS AND METHODS: The authors studied
      five types of covered metal stents. Type A stents were nonretrievable
      polyurethane-covered stents with shouldered ends (n = 169), type B stents were
      retrievable polyurethane-covered stents with shouldered ends (n = 62), type C
      stents were retrievable polyurethane-covered stents with flared ends (n = 72),
      type D stents were retrievable polytetrafluoroethylene-covered stents with
      shouldered ends (n = 369), and type E stents were separated stents (n = 216).
      Types A-D stents were esophageal stents, and the type E stent was a
      gastroduodenal stent. Stents were placed in 888 patients with either benign (n =
      43) or malignant (n = 845) causes of stricture. The rate of stent migration was
      analyzed relative to completeness of migration, the cause of obstruction, stent
      type, and stent placement location. The fate of migrated stents and the treatment
      of patients were evaluated. RESULTS: Stent migration occurred in 70 of the 888
      patients (7.9%). Migration occurred in 11 of the 43 patients (25%) with benign
      cause of strictures and 591 of the 845 patients (7.0%) with malignant cause. The
      migration rates for types A, B, C, D, and E stents were 10%, 4.8%, 24%, 7.3% and
      2.8%, respectively. Of the 70 migrated stents, 45 had complete migration and 25
      had partial migration. The anastomotic sites were the areas most commonly
      associated with migration (16%), but this was not statistically significant.
      Forty of the 70 migrated stents were removed with retrieval devices under
      fluoroscopic guidance because they were not passed with stool and possibility of
      complications related to migrated stents. The remaining 30 stents exited via the
      rectum (n = 15), remained in the body without complications (n = 12), or were
      surgically removed because they caused complicated intestinal obstructions (n =
      3). CONCLUSION: The overall migration rate for esophageal and gastroduodenal
      stents was 7.9%. Most migrated stents were removed nonsurgically, exited the body
      spontaneously, or remained in the body in an uncomplicated state. Surgical stent
      removal was necessary in three patients (4.3%) due to complicated intestinal
      obstructions.

PMID- 17538135
TI  - Percutaneous radiofrequency ablation of lung tumors close to the heart or aorta:
      evaluation of safety and effectiveness.
AB  - PURPOSE: The authors retrospectively evaluated the safety and effectiveness of
      percutaneous radiofrequency ablation of lung tumors close to the heart or aorta.
      MATERIALS AND METHODS: Forty-two tumors (mean diameter, 25 mm +/- 16; range, 5-73
      mm) located less than 10 mm from the heart or aorta were treated with
      radiofrequency ablation in 47 sessions. Lung tumors were classified into two
      groups according to their distance from the heart or aorta: group A (n = 27)
      comprised tumors at a distance of 1-9 mm; group B (n = 15) comprised contiguous
      tumors (distance, 0 mm). The safety and technique effectiveness of the procedure,
      defined as no evidence of local tumor progression, were evaluated. RESULTS:
      Radiofrequency ablation was feasible for all the 42 tumors. Procedural
      complications included asymptomatic pleural effusion (n = 5), small pneumothorax
      (n = 11), pneumothorax that necessitated chest tube placement (n = 4), and lung
      abscess (n = 1). No complications related to the specific tumor location, such as
      the accidental insertion of the electrode into the heart or aorta, pericardial
      effusion, arrhythmia, or cardiac infarction, occurred. The overall primary
      technique effectiveness rate was 75.8%, 45.9%, and 45.9% at 6, 12, and 24 months,
      respectively. This rate in group A (94.7%, 69.3%, and 69.3% at 6, 12, and 24
      months, respectively) was significantly (P < .001) higher than that in group B
      (42.9% and 8.6% at 6 and 12 months, respectively). CONCLUSIONS: Radiofrequency
      ablation of lung tumors close to the heart or aorta was safely performed. The
      local control of tumors contiguous to the heart or aorta was considerably lower
      compared with the tumors that were close but not contiguous to these structures.

PMID- 17538136
TI  - Treatment of vertebral tumor with posterior wall defect using image-guided
      radiofrequency ablation combined with vertebroplasty: preliminary results in 12
      patients.
AB  - PURPOSE: To evaluate the safety and clinical benefit of vertebral tumor treatment
      by combined radiofrequency ablation (RFA) and vertebroplasty, for pain reduction
      in patients who are unable to benefit from noninvasive treatment methods.
      MATERIALS AND METHODS: Twelve patients with painful vertebral tumors with
      posterior wall defect, in whom medical treatment together with radiation therapy
      and/or chemotherapy had failed, were treated with RFA combined with
      vertebroplasty. Procedures were performed using multislice CT-fluoroscopy and
      lateral C-arm fluoroscopic guidance. All patients had posterior wall defects of
      the vertebra being treated. Ten had lytic posterior wall destruction and two had
      posterior wall fracture. The visual analog scale (VAS) pain score was measured
      before, one week after, and three months after treatment. VAS patient
      satisfaction score was measured before and one week after treatment. The VAS
      score range was 0-20. The analgesic use was evaluated before and four weeks after
      treatment and complications were monitored. RESULTS: Combined RFA and
      vertebroplasty treatment was technically successful in all patients. Pain
      significantly decreased after treatment: the mean VAS pain score before treatment
      was 17.33 +/- 2.46 (range, 13-20) versus 9.25 +/- 4.81 (range, 2-18) one week
      after treatment (P < .001) and was 7.00 +/- 5.26 (range, 1-14) three months after
      treatment (P = .020). The mean VAS satisfaction score of all patients was 15.83
      +/- 4.26 (range, 4-20). Analgesic use decreased after treatment. No serious
      treatment related complications occurred. CONCLUSION: RFA in combination with
      vertebroplasty for treating vertebral tumors with posterior wall defect appeared
      safe, and reduced pain substantially in patients who did not benefit from other
      noninvasive treatment methods.

PMID- 17538137
TI  - Respiratory biofeedback during CT-guided procedures.
AB  - PURPOSE: Respiratory motion can be a complicating factor during image-guided
      interventions. The ability to reproduce breath-holds may facilitate safer needle
      based procedures. The purpose of this study was to evaluate if respiratory
      biofeedback decreased variability among breath-holds and if the signals from the
      respiratory bellows belt can be used to measure target motion. MATERIALS AND
      METHODS: In phase 1 of the study, a respiratory bellows belt was applied to
      patients before image-guided interventional procedures. Belt stretch from
      respiratory motion was converted into voltage readings and displayed on a monitor
      as biofeedback. Patients were asked to perform inspiratory, expiratory, and
      midcycle breath-holds with and without the biofeedback. The variability in
      voltage readings between breath-holds with and without biofeedback was compared.
      In phase 2, the respiratory bellows belt was used during computed tomography (CT)
      guided procedures with the patients blinded to the biofeedback. Voltage readings
      and CT series numbers were recorded as patients were asked to hold their breath
      during scans. The variability of CT z-axis targets was compared with the
      variability of voltage readings. RESULTS: A significant decrease in variability
      was found during expiratory breath-holds (P = .0083) with trends toward
      significance with midcycle and inspiratory breath-holds. A positive correlation
      (Kendall tau = 0.5; P = .024) was shown between CT z-axis and belt stretch
      variability in subjects who received smaller doses of moderate sedation compared
      with those who received larger doses or general anesthesia. CONCLUSIONS:
      Biofeedback may help the patient to have a more consistent breath-hold. The belt
      could decrease the error and unpredictability from craniocaudal motion of targets
      during image-guided interventions.

PMID- 17538138
TI  - Efficacy of mitomycin-C irrigation after balloon dacryocystoplasty.
AB  - PURPOSE: To evaluate the safety and efficacy of mitomycin-C irrigation after
      balloon dacryocystoplasty in the treatment of epiphora caused by obstruction of
      the lacrimal system. MATERIALS AND METHODS: Thirty-five lacrimal systems in 33
      patients with obstruction of the lacrimal system were assigned to one of two
      groups: 17 lacrimal systems were irrigated with mitomycin-C after balloon
      dacryocystoplasty (mytomycin-C group), and 18 were not irrigated with mitomycin-C
      after balloon dacryocystoplasty (non-mitomycin-C group). In the mitomycin-C
      group, the lacrimal systems were irrigated with 0.2 mg/mL mitomycin-C via the
      inferior lacrimal punctum in three different sessions: immediately, 1 week, and 1
      month after balloon dacryocystoplasty. The cumulative patency rates after balloon
      dacryocystoplasty were calculated by using the Kaplan-Meier method and were
      compared between the two groups with use of the log-rank test. RESULTS: Balloon
      dacryocystoplasty and subsequent mitomycin-C irrigation were technically
      successful in all lacrimal systems. There were no side effects or complications
      associated with mitomycin-C use. The cumulative patency rate in the mitomycin-C
      group was significantly higher than that in the non-mitomycin-C group after
      balloon dacryocystoplasty (P = .0150, log-rank test). CONCLUSIONS: Mitomycin-C
      irrigation is safe and effective in increasing the patency rate of the lacrimal
      system after balloon dacryocystoplasty.

PMID- 17538139
TI  - Sealing of type III endoleaks with ethylene vinyl alcohol copolymer in a canine
      model.
AB  - PURPOSE: To test ethylene vinyl alcohol copolymer (EVOH) as a sealing agent for
      persistent abdominal aortic aneurysm (AAA) endograft leaks. MATERIALS AND
      METHODS: Twelve dogs underwent creation of AAAs with a Palmaz P4014 stent. A 10
      mm x 5-cm Wallgraft endoprosthesis with a 4-mm-diameter hole cut into its side
      was deployed within the AAA. One week later, computed tomography (CT) and
      angiography were performed and the aneurysm sac was catheterized through the 4-mm
      hole. Then, EVOH was injected into the sac and lumbar arteries. Four weeks
      thereafter, all surviving animals underwent repeat CT scanning and angiography
      and were then euthanized. The AAA underwent gross and microscopic study. RESULTS:
      Three dogs died from aortic rupture within 24 hours of AAA creation and the
      remaining nine dogs survived to receive EVOH. All nine dogs had persistent flow
      into the sac and lumbar arteries at the time of EVOH delivery. Seven dogs
      survived to the end of the experiment, and all aneurysm sacs and lumbar arteries
      remained occluded on angiography and CT. Histologic examination revealed EVOH and
      thrombus admixed, with thrombus in varying stages of organization filling the
      aneurysm sac and lumbar arteries. CONCLUSIONS: Embolization of type III endoleaks
      with EVOH proved to be feasible in a canine model. Further work is warranted to
      determine its therapeutic utility.

PMID- 17538140
TI  - Superselective coil embolization of arterial esophageal hemorrhage.
AB  - The authors report a case of arterial esophageal bleeding resistant to endoscopic
      hemostasis in a patient in critical condition after complicated gastrointestinal
      and pulmonary surgery. Unfit for surgery, the patient's massive hemorrhage was
      successfully treated with superselective coil embolization of the afferent
      esophageal branch of the thoracic aorta. In patients with severe arterial
      bleeding of the esophagus, percutaneous superselective arterial coil embolization
      may be feasible for control of hemorrhage.

PMID- 17538141
TI  - Endovascular covered stent repair of an iatrogenic subclavian artery-to-pulmonary
      artery fistula and pseudoaneurysm.
AB  - An iatrogenic fistula and consequent pseudoaneurysm developed between the right
      subclavian artery and right pulmonary artery as a result of misplacement of a
      hemodialysis access catheter. The patient, who was considered to be at high risk
      for surgical repair, successfully underwent endovascular treatment that involved
      insertion of two nitinol stents covered with expanded polytetrafluoroethylene
      (stent-grafts), one into the right subclavian artery and the other into a right
      upper lobe pulmonary artery. Multi-detector row computed tomographic angiography
      played an integral role in the evaluation of the patient's vascular injury and
      treatment planning.

PMID- 17538142
TI  - Embolization of an arterioportal fistula by injection of D-stat into the portal
      venous outflow.
AB  - Arterioportal fistulas may occur in liver transplant recipients after
      percutaneous biopsy. This report describes a case in which a 13-year-old liver
      transplant patient developed an arterioportal fistula after multiple liver
      biopsies and underwent coil embolization; however, at that time, there were at
      least two small arterial feeders that were not amenable to subselection. He later
      developed recurrent variceal bleeding, and repeat angiogram revealed multiple
      tiny serpentine feeding arteries. Because these arteries could not be
      subselectively catheterized, the collagen-thrombin mixture, D-Stat, was used to
      occlude the portal venous outflow of the arterioportal fistula. Subsequent
      angiography demonstrated successful complete occlusion of the arterioportal
      fistula.

PMID- 17538143
TI  - Pulsatility imaging of saccular aneurysm model by 64-slice CT with dynamic
      multiscan technique.
AB  - The feasibility of imaging pulsatility in an aneurysm model with the high
      resolution dynamic multiscan technique of 64-slice computed tomography (CT) was
      studied. A pulsatile aneurysm phantom was constructed and imaged with dynamic
      multiscan technique. The aneurysm model was filled with iodinated contrast
      material (250 Hounsfield Units) and was scanned with use of a gantry rotation
      time of 0.33 seconds, slice thickness of 1.2 mm, effective coverage of 24 mm, and
      total imaging time of 4 seconds. Images were reconstructed at 50-msec intervals.
      The visualization of wall motion was qualitatively evaluated by direct comparison
      of four-dimensional images versus phantom motion. Pulsatility imaging without
      perceptible artifact or need for cardiac gating was achieved with the use of this
      technique.

PMID- 17538144
TI  - Focal myometrial defect and partial placenta accreta in a pregnancy following
      bilateral uterine artery embolization.
AB  - A 29-year-old nulliparous patient was treated with uterine artery embolization
      (UAE) for a large symptomatic uterine fibroid, resulting in a marked reduction of
      the tumor volume. She subsequently conceived and progressed through pregnancy
      uneventfully. At cesarean section for breech presentation at term, a large fundal
      myometrial defect was encountered. In addition, the patient presented with
      unexpected partial placenta accreta, which resulted in massive atonic uterine
      bleeding. It is suggested that UAE was implicated in the pathogenesis of
      myometrial damage and abnormal placentation. It is proposed that the antenatal
      care of pregnancies after UAE include careful imaging of the placenta, its
      vasculature, and the thickness of overlying uterine wall so peripartum management
      can be appropriately planned.

PMID- 17538145
TI  - Bilateral pneumothorax after unilateral transthoracic puncture.
AB  - Pneumothorax is a common complication following transthoracic interventional
      procedures. Most often, this occurs unilaterally on the side of the intervention.
      Bilateral pneumothorax following unilateral puncture is rare, but may mandate
      emergent chest tube insertion. We describe two cases in which bilateral
      pneumothorax occurred after unilateral thoracic puncture. One patient had a
      history of esophageal resection, while the other had no history of thoracic
      surgery.

PMID- 17538146
TI  - Retrograde percutaneous enterostomies in children using a needle system with
      valve mechanism.
AB  - The technique of enterostomy access frequently uses a needle preloaded with a
      suture anchor to appose the bowel wall to the abdominal wall. Two of the
      intrinsic disadvantages of this method are the possible dislodgment of the suture
      anchor out of the needle hub during the process of guide-wire insertion and the
      escape of air with subsequent deflation of the viscus, which may necessitate a
      second puncture. The use of a Check-Flo performer assembly with a valve mechanism
      provides a leakproof system. It avoids possible dislodgment of the suture anchor
      during deployment, maintains viscus distension, and may be useful for trainees to
      do the procedure in a controlled manner.

PMID- 17538147
TI  - Initial report of PET/CT-guided radiofrequency ablation of liver metastases.
AB  - Computed tomography (CT) and ultrasonography (US) are commonly employed to guide
      positioning of radiofrequency electrodes within target tumors. However, this
      technique cannot be used when the tumor is detectable only by positron emission
      tomography (PET). In such cases, even the use of intraprocedural coregistered
      PET/CT will not prevent malpositioning of the electrode tip relative to a lesion
      visualized only on PET as a result of patient breathing and organ shifts during
      CT-guided electrode placement. The present report describes a single case of
      successful targeting and complete ablation of a lesion invisible on CT and US
      with the use of a method to visualize electrode tip positioning by PET.

PMID- 17538148
TI  - Percutaneous osteoplasty with use of a cement-filled catheter for a pathologic
      fracture of the humerus.
AB  - Percutaneous osteoplasty has been used for pathologic fractures of long bones as
      an adjunct to orthopedic surgery. The present report describes a case of
      percutaneous osteoplasty with a cement-filled catheter and cement augmentation as
      the principal therapy to unite a painful pathologic fracture of the humerus.
      After the procedure, the patient experienced immediate pain relief and improved
      limb mobility. Percutaneous osteoplasty with this method holds promise as a
      treatment for pathologic fractures of the humerus that are not amenable to
      surgical repair.

PMID- 17538149
TI  - Re: endovenous laser ablation of the great saphenous vein with a 980-nm diode
      laser in continuous mode: early treatment failures and successful repeat
      treatments.

PMID- 17538151
TI  - Percutaneous removal of a knotted pulmonary artery catheter using sheaths and
      parallel crossing wires.

PMID- 17538152
TI  - Caudal migration of a G2 filter during carbon dioxide cavography.

PMID- 17538153
TI  - Complete, long-standing regression of hepatocellular carcinoma after somatostatin
      analogue treatment.

PMID- 17538154
TI  - Relief of symptoms after gefitinib is associated with improvement of
      rest/activity rhythm in advanced lung cancer.

PMID- 17538156
TI  - Journal honors Donald Parsons, MD, PhD, as recipient of the 2007 JCO Young
      Investigator Award.

PMID- 17538155
TI  - Molecular classification of patients with malignant melanoma for new therapeutic
      strategies.

PMID- 17538157
TI  - Epidermal growth factor receptor inhibition in head and neck cancer--more
      insights, but more questions.

PMID- 17538158
TI  - Combination chemotherapy in advanced pancreatic cancer: time to raise the white
      flag?

PMID- 17538159
TI  - Moving forward in advanced bladder cancer.

PMID- 17538160
TI  - Epidermal growth factor receptor copy number alterations correlate with poor
      clinical outcome in patients with head and neck squamous cancer.
AB  - PURPOSE: Overexpression of epidermal growth factor receptor (EGFR) is common in
      head and neck squamous cell carcinoma (HNSCC). Recent studies showed that EGFR
      inhibitors are effective for patients with HNSCC. This study analyzed the genetic
      nature of EGFR gene in HNSCC and its clinical correlations. PATIENTS AND METHODS:
      The EGFR gene copy numbers in 134 HNSCC tumors were determined using quantitative
      real-time polymerase chain reaction. The status of EGFR gene copy numbers was
      analyzed with clinical parameters including clinical outcome. Mutation status of
      EGFR exons 18, 19, and 21 was determined in the HNSCC tumors. RESULTS: Aberrant
      EGFR copy numbers were found in 32 (24%) of 134 tumors, including 22 (17%) with
      increased copy number and 10 (7%) with decreased copy number. Patients whose
      tumors had EGFR copy number alterations (particularly patients with increased
      copy numbers) had significantly poorer overall, cancer-specific, and disease-free
      survivals compared with patients with normal copy numbers (P < .0001). At 5 years
      after initial diagnosis, 20 (91%) of the 22 patients with increased copy numbers
      died of disease compared with 30 (29%) of the 102 patients with normal copy
      number. No mutations on EGFR exons 18, 19, and 21 were detected in any of the
      tumors. CONCLUSION: A subset of HNSCC manifests EGFR copy number alterations, and
      this is associated with a poor clinical outcome, suggesting a biologic role of
      the alterations. The rare mutation or small deletion at EGFR exons 18 to 21
      indicates a minimal role of these events in HNSCC.

PMID- 17538161
TI  - Open-label, uncontrolled, multicenter phase II study to evaluate the efficacy and
      toxicity of cetuximab as a single agent in patients with recurrent and/or
      metastatic squamous cell carcinoma of the head and neck who failed to respond to
      platinum-based therapy.
AB  - PURPOSE: To evaluate the efficacy and safety of the epidermal growth factor
      receptor-directed monoclonal antibody cetuximab administered as a single agent in
      patients with recurrent and/or metastatic squamous cell carcinoma of the head and
      neck (SCCHN) who experience disease progression on platinum therapy. PATIENTS AND
      METHODS: An open-label multicenter study in which patients with disease
      progression on two to six cycles of platinum therapy received single-agent
      cetuximab (initial dose 400 mg/m2 followed by subsequent weekly doses of 250
      mg/m2) for > or = 6 weeks (single-agent phase). Patients who experienced disease
      progression could receive salvage therapy with cetuximab plus platinum
      (combination-therapy phase). From June 2001 to December 2002, 103 patients were
      enrolled and treated with cetuximab, 53 of whom subsequently received combination
      therapy. RESULTS: In the single-agent phase, response rate was 13%, disease
      control rate (complete response/partial response/stable disease) was 46%, and
      median time to progression (TTP) was 70 days. During the combination-therapy
      phase, the objective response rate was zero, disease control rate was 26%, and
      TTP was 50 days. Median overall survival was 178 days. Treatment was well
      tolerated. The most common cetuximab-related adverse events in the single-agent
      phase were skin reactions, particularly rash (49% of patients, mainly grade 1 or
      2). There was one treatment-related death due to an infusion-related reaction.
      CONCLUSION: Single-agent cetuximab was active and generally well tolerated in the
      treatment of recurrent and/or metastatic SCCHN that progressed on platinum
      therapy. Response was comparable to that seen with cetuximab plus platinum
      combination regimens in the same setting.

PMID- 17538162
TI  - Phase I/II trial of erlotinib and cisplatin in patients with recurrent or
      metastatic squamous cell carcinoma of the head and neck: a Princess Margaret
      Hospital phase II consortium and National Cancer Institute of Canada Clinical
      Trials Group Study.
AB  - PURPOSE: To determine the phase II dose and objective response rate of erlotinib,
      a selective epidermal growth factor receptor tyrosine kinase inhibitor, in
      combination with cisplatin in patients with recurrent or metastatic squamous cell
      carcinoma of the head and neck (HNSCC). PATIENTS AND METHODS: HNSCC patients with
      no prior chemotherapy and measurable disease were treated in three escalating
      dose cohorts of daily continuous oral (PO) erlotinib and intermittent intravenous
      (IV) cisplatin given every 21 days. The recommended phase II dose (RPTD) was then
      evaluated in a two-stage trial with a primary end point of objective response
      rate. RESULTS: A total of 51 patients were enrolled. The RPTD was identified as
      erlotinib 100 mg PO daily and cisplatin 75 mg/m2 IV every 21 days. Forty-five
      patients were treated at the RPTD, of which 44 and 43 were eligible for toxicity
      and efficacy evaluations, respectively. The intention-to-treat response rate was
      21%, with one complete and eight partial responses (95% CI, 10% to 36%), and
      disease stabilization was achieved in 21 patients (49%; 95% CI, 33% to 65%).
      Median progression-free survival was 3.3 months (95% CI, 2.7 to 4.8 months) and
      median overall survival was 7.9 (95% CI, 5.6 to 9.5) months. The combination was
      well tolerated, with minimal grade 3 or higher toxicity. Subgroup analysis
      suggested that patients who developed higher grade skin rashes during cycle 1 had
      better survival outcomes (P = .034). CONCLUSION: This schedule of erlotinib and
      cisplatin has a favorable toxicity profile and has antitumor activity in HNSCC
      comparable to standard combination chemotherapy regimens.

PMID- 17538163
TI  - Predictive and pharmacodynamic biomarker studies in tumor and skin tissue samples
      of patients with recurrent or metastatic squamous cell carcinoma of the head and
      neck treated with erlotinib.
AB  - PURPOSE Pharmacodynamic tissue studies were conducted on a phase I/II trial of
      erlotinib and cisplatin in patients with recurrent or metastatic head and neck
      squamous cell carcinoma (HNSCC). Levels of epidermal growth factor receptor
      (EGFR), downstream signaling components, and markers of angiogenesis and
      apoptosis were evaluated to determine the relationship between correlative end
      points and clinical outcomes. PATIENTS AND METHODS Pretreatment and during
      treatment tumor and skin biopsies, and archival tumor specimens were evaluated
      for EGFR, phosphorylated (p) -EGFR, extracellular signal-regulated kinase (ERK),
      p-ERK, Akt, p-Akt, Ki67, p27, p-nuclear factor kappa B (NFkappaB), p-signal
      transducer and activator of transcription 3 (STAT3), and EGFR gene copy number.
      Results On 37 archival samples, response to therapy was evident in two of four
      (50%) patients with high EGFR gene copy number tumors and in four of 27 (15%)
      patients with low gene copy number tumors. On nine paired tumor biopsies,
      elevated pretreatment levels of p27 and p-STAT3 predicted for prolonged time to
      progression (TTP) and overall survival (OS; P < or = .03). With treatment, a
      decrease in p-EGFR, p-NFkappaB, and p27 correlated with increased TTP, OS, or
      both TTP and OS, respectively (P < or = .04). Multidimensional scaling (MDS)
      models revealed clustering profiles of tumor markers by immunofluorescence could
      predict response. On 32 paired skin biopsies, suppression of p-EGFR with therapy
      correlated with increased OS (P = .045). CONCLUSION High EGFR gene copy in tumor
      specimens may predict which patients have an increased likelihood of response to
      erlotinib, and decreased p-EGFR level in skin biopsies during therapy may
      represent a potential surrogate marker for improved clinical outcome. MDS
      represents a novel way to evaluate the relationships between molecular markers
      and clinical outcome. Additional biomarker studies with larger sample sizes are
      required to elucidate HNSCC patients who may benefit from this targeted therapy.

PMID- 17538164
TI  - Quality of life in head and neck cancer patients after treatment with high-dose
      radiotherapy alone or in combination with cetuximab.
AB  - PURPOSE: In this randomized, phase III study, quality of life (QoL) was assessed
      in patients with locoregionally advanced squamous cell carcinoma of the head and
      neck (SCCHN) after high-dose radiotherapy alone or in combination with cetuximab.
      PATIENTS AND METHODS: Patients with stage III or IV nonmetastatic and measurable
      squamous cell carcinoma of the oropharynx, hypopharynx, or larynx were eligible.
      QoL was assessed using the European Organisation for Research and Treatment of
      Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30) and EORTC QLQ Head and
      Neck Cancer-Specific Module at baseline, week 4, and at months 4, 8, and 12
      postbaseline. RESULTS: In this study, one of the largest conducted in a
      population of patients with locoregionally advanced SCCHN, 424 patients received
      radiotherapy alone (213 patients) or radiotherapy plus cetuximab (211 patients).
      Radiotherapy/cetuximab significantly improved locoregional control (P = .005) and
      overall survival (P = .03) compared with radiotherapy alone, without
      significantly increasing radiotherapy-associated adverse events. The current
      analysis focused on the impact of cetuximab on the QoL. Compliance with
      completion of QoL questionnaires was high in both arms. QoL worsened during
      treatment and improved after cessation of treatment, reaching baseline levels at
      12 months. There were no significant differences in QoL scores between the
      treatment arms. This was particularly notable for global health status/QoL,
      social functioning, social eating, and social contact. Pretreatment global health
      status/QoL was identified as a significant prognostic variable in these patients.
      CONCLUSION: The addition of cetuximab to radiotherapy significantly improved
      locoregional control and increased overall survival without adversely affecting
      QoL.

PMID- 17538165
TI  - Gemcitabine plus capecitabine compared with gemcitabine alone in advanced
      pancreatic cancer: a randomized, multicenter, phase III trial of the Swiss Group
      for Clinical Cancer Research and the Central European Cooperative Oncology Group.
AB  - PURPOSE: This phase III trial compared the efficacy and safety of gemcitabine
      (Gem) plus capecitabine (GemCap) versus single-agent Gem in advanced/metastatic
      pancreatic cancer. PATIENTS AND METHODS: Patients were randomly assigned to
      receive GemCap (oral capecitabine 650 mg/m2 twice daily on days 1 to 14 plus Gem
      1,000 mg/m2 by 30-minute infusion on days 1 and 8 every 3 weeks) or Gem (1,000
      mg/m2 by 30-minute infusion weekly for 7 weeks, followed by a 1-week break, and
      then weekly for 3 weeks every 4 weeks). Patients were stratified according to
      center, Karnofsky performance score (KPS), presence of pain, and disease extent.
      RESULTS: A total of 319 patients were enrolled between June 2001 and June 2004.
      Median overall survival (OS) time, the primary end point, was 8.4 and 7.2 months
      in the GemCap and Gem arms, respectively (P = .234). Post hoc analysis in
      patients with good KPS (score of 90 to 100) showed a significant prolongation of
      median OS time in the GemCap arm compared with the Gem arm (10.1 v 7.4 months,
      respectively; P = .014). The overall frequency of grade 3 or 4 adverse events was
      similar in each arm. Neutropenia was the most frequent grade 3 or 4 adverse event
      in both arms. CONCLUSION: GemCap failed to improve OS at a statistically
      significant level compared with standard Gem treatment. The safety of GemCap and
      Gem was similar. In the subgroup of patients with good performance status, median
      OS was improved significantly. GemCap is a practical regimen that may be
      considered as an alternative to single-agent Gem for the treatment of
      advanced/metastatic pancreatic cancer patients with a good performance status.

PMID- 17538166
TI  - Trastuzumab, paclitaxel, carboplatin, and gemcitabine in advanced human epidermal
      growth factor receptor-2/neu-positive urothelial carcinoma: results of a
      multicenter phase II National Cancer Institute trial.
AB  - PURPOSE: We investigated the safety and efficacy (response rates, time to disease
      progression, survival) of trastuzumab, carboplatin, gemcitabine, and paclitaxel
      in advanced urothelial carcinoma patients and prospectively evaluated human
      epidermal growth factor receptor-2 (Her-2/neu) overexpression rates. PATIENTS AND
      METHODS: Advanced urothelial carcinoma patients were screened for Her-2/neu
      overexpression. Eligibility for therapy required human epidermal growth factor
      receptor-2 (Her-2/neu) overexpression by immunohistochemistry (IHC), gene
      amplification and/or elevated serum Her-2/neu, no prior chemotherapy for
      metastasis, and adequate organ function including a normal cardiac function.
      Treatment consisted of trastuzumab (T) 4 mg/kg loading dose followed by 2 mg/kg
      on days 1, 8, and 15; paclitaxel (P) 200 mg/m2 on day 1; carboplatin (C; area
      under the curve, 5) on day 1; and gemcitabine (G) 800 mg/m2 on days 1 and 8. The
      primary end point was cardiac toxicity. RESULTS: Fifty-seven (52.3%) of 109
      registered patients were Her-2/neu positive, and 48.6% were positive by IHC. Her
      2/neu-positive patients had more metastatic sites and visceral metastasis than
      did Her-2/neu negative patients. Forty-four of 57 Her-2/neu-positive patients
      were treated with TPCG. The median number of cycles was six (range, 1 to 12
      cycles). The most common grade 3/4 toxicity was myelosuppression. Grade 3 sensory
      neuropathy occurred in 14% of patients, and 22.7% experienced grade 1 to 3
      cardiac toxicity (grade 3, n = 2: one left ventricular dysfunction, one
      tachycardia). There were three [corrected] therapy-related deaths. Thirty-one
      (70%) of 44 patients responded (five complete and 26 partial), and 25 (57%) of 44
      were confirmed responses. Median time to progression and survival were 9.3 and
      14.1 months, respectively. CONCLUSION: We prospectively characterized Her-2/neu
      status in advanced urothelial carcinoma patients. TPCG is feasible; cardiac
      toxicity rates were higher than projected, but the majority were grade two or
      lower. Determining the true contribution of trastuzumab requires a randomized
      trial.

PMID- 17538167
TI  - Predominant treatment failure in postprostatectomy patients is local: analysis of
      patterns of treatment failure in SWOG 8794.
AB  - PURPOSE: Southwest Oncology Group (SWOG) trial 8794 demonstrated that adjuvant
      radiation reduces the risk of biochemical (prostate-specific antigen [PSA])
      treatment failure by 50% over radical prostatectomy alone. In this analysis, we
      stratified patients as to their preradiation PSA levels and correlated it with
      outcomes such as PSA treatment failure, local recurrence, and distant failure, to
      serve as guidelines for future research. PATIENTS AND METHODS: Four hundred
      thirty-one subjects with pathologically advanced prostate cancer (extraprostatic
      extension, positive surgical margins, or seminal vesicle invasion) were randomly
      assigned to adjuvant radiotherapy or observation. RESULTS: Three hundred seventy
      four eligible patients had immediate postprostatectomy and follow-up PSA data.
      Median follow-up was 10.2 years. For patients with a postsurgical PSA of 0.2
      ng/mL, radiation was associated with reductions in the 10-year risk of
      biochemical treatment failure (72% to 42%), local failures (20% to 7%), and
      distant failures (12% to 4%). For patients with a postsurgical PSA between higher
      than 0.2 and <or = 1.0 ng/mL, reductions in the 10-year risk of biochemical
      failure (80% to 73%), local failures (25% to 9%), and distant failures (16% to
      12%) were realized. In patients with postsurgical PSA higher than 1.0, the
      respective findings were 94% versus 100%, 28% versus 9%, and 44% versus 18%.
      CONCLUSION: The pattern of treatment failure in high-risk patients is
      predominantly local with a surprisingly low incidence of metastatic failure.
      Adjuvant radiation to the prostate bed reduces the risk of metastatic disease and
      biochemical failure at all postsurgical PSA levels. Further improvement in
      reducing local treatment failure is likely to have the greatest impact on outcome
      in high-risk patients after prostatectomy.

PMID- 17538168
TI  - MDM2 polymorphism, survival, and histology in early-stage non-small-cell lung
      cancer.
AB  - PURPOSE: MDM2 is a negative regulator of p53. The MDM2 309T/G polymorphism has
      been associated with differential MDM2 expression levels and inhibition of the
      p53 pathway. We hypothesized that the MDM2 G/G genotype may be associated with
      worse survival outcomes in lung cancer, especially in squamous cell cancers where
      p53 abnormalities are more common. PATIENTS AND METHODS: We evaluated the
      relationship between MDM2 polymorphism status and overall survival (OS) among
      patients with early-stage non-small-cell lung cancer (NSCLC) treated with
      surgical resection at Massachusetts General Hospital from 1992 to 2000. Kaplan
      Meier methods and the log-rank test were used to compare survival by polymorphism
      status. Cox proportional hazards models were used to adjust for possible
      confounding variables. RESULTS: There were 383 patients in the analysis. In the
      early-stage population as a whole, the G/G genotype seemed to be associated with
      worse OS on adjusted analysis (adjusted hazard ratio = 1.57; 95% CI, 1.03 to
      2.40; P = .04). Among patients with squamous histology, OS was significantly
      worse among those with the G/G genotype (P = .0001 by log-rank test), with 5-year
      survival rates among the genotypes of 59% for T/T, 53% for T/G, and 7% for G/G.
      CONCLUSION: Our findings suggest that the G/G genotype of the MDM2 polymorphism
      is associated with worse OS among early-stage NSCLC patients, particularly those
      with squamous cell histology.

PMID- 17538169
TI  - Prospective study of gefitinib in epidermal growth factor receptor fluorescence
      in situ hybridization-positive/phospho-Akt-positive or never smoker patients with
      advanced non-small-cell lung cancer: the ONCOBELL trial.
AB  - PURPOSE: In non-small-cell lung cancer (NSCLC), clinical and biologic predictors
      for epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor sensitivity
      have been identified in retrospective studies, and there is urgent need to
      validate these results in prospective trials. The ONCOBELL trial is a prospective
      phase II study evaluating gefitinib sensitivity in NSCLC patients who never
      smoked or have increased EGFR gene copy number or activation of the antiapoptotic
      protein Akt. PATIENTS AND METHODS: EGFR gene copy number was evaluated using
      fluorescence in situ hybridization (FISH), and presence of phospho-Akt was
      evaluated using immunohistochemistry. Additional tests included
      immunohistochemistry analysis of EGFR, FISH analysis of HER2, and mutation
      analysis of EGFR, HER2, and K-ras. RESULTS: From November 2004 to February 2006,
      183 patients were screened, and 42 patients were enrolled onto the trial. We
      observed one complete and 19 partial responses, for an overall response rate (RR)
      of 47.6% (95% CI, 32.5% to 62.7%). Median duration of response was 6.1 months,
      median time to progression (TTP) was 6.4 months, 1-year survival rate was 64.3%,
      and median survival time was not reached. EGFR FISH-positive patients, compared
      with negative patients, had higher RR (68.0% v 9.1%, respectively; P < .001),
      longer TTP (7.6 v 2.7 months, respectively; P = .02), and a trend for longer
      survival (median survival not reached v 7.4 months, respectively; P = .3).
      Therapy was well tolerated, and there were no drug-related deaths. Median follow
      up time was too short for significance tests of differences in survival outcomes.
      CONCLUSION: Gefitinib is active and well tolerated in patients with trial
      characteristics, and EGFR FISH analysis is an accurate predictor for such
      therapy.

PMID- 17538170
TI  - Economic analysis of NCIC CTG JBR.10: a randomized trial of adjuvant vinorelbine
      plus cisplatin compared with observation in early stage non-small-cell lung
      cancer--a report of the Working Group on Economic Analysis, and the Lung Disease
      Site Group, National Cancer Institute of Canada Clinical Trials Group.
AB  - PURPOSE: National Cancer Institute of Canada Clinical Trials Group JBR.10 study
      is among the landmark trials that have established third generation platinum
      based adjuvant chemotherapy as the standard of care after resection of stages IB
      II NSCLC, improving absolute 5-year survival by 15% and median survival by 21
      months. This cost-effectiveness analysis of adjuvant chemotherapy from the
      perspective of Canada's public health care system was undertaken based on the
      JBR.10 study population. PATIENTS AND METHODS: The primary outcome of the study
      was the incremental cost effectiveness ratio (ICER) expressed in dollars per life
      year gained (LYG). Direct medical resource utilization data were collected
      retrospectively from trial data and medical records of patients enrolled in the
      JBR.10 study at the five largest accruing Canadian centers, from the time of
      random assignment until death or study closure (April 2004). Survival and
      available costs (2005 Canadian dollars [$CAD]) are presented both with and
      without discounting at 5% per year. RESULTS: Utilization data were collected from
      172 Canadian patients (36% of the trial population), 85 randomly assigned to
      observation and 87 randomly assigned to chemotherapy. The mean costs of treatment
      per patient in the observation and adjuvant chemotherapy arms were $23,878 and
      $31,319, respectively, with an ICER of CAD$7,175/LYG discounted (95% CI, -$3,463
      to $41,565), and $10,096/LYG undiscounted (95% CI, -$819 to $55,651). CONCLUSION:
      Adjuvant vinorelbine plus cisplatin is a highly cost effective treatment that
      compares very favorably with other standard health care interventions.

PMID- 17538171
TI  - Superiority of fluorodeoxyglucose positron emission tomography to other
      functional imaging techniques in the evaluation of metastatic SDHB-associated
      pheochromocytoma and paraganglioma.
AB  - PURPOSE: Germline mutations of the gene encoding subunit B of the mitochondrial
      enzyme succinate dehydrogenase (SDHB) predispose to malignant paraganglioma
      (PGL). Timely and accurate localization of these aggressive tumors is critical
      for guiding optimal treatment. Our aim is to evaluate the performance of
      functional imaging modalities in the detection of metastatic lesions of SDHB
      associated PGL. PATIENTS AND METHODS: Sensitivities for the detection of
      metastases were compared between [18F]fluorodopamine ([18F]FDA) and [18F]fluoro-2
      deoxy-D-glucose (FDG) positron emission tomography (PET), iodine-123- (123I) and
      iodine-131 (131I) -metaiodobenzylguanidine (MIBG), 111In-pentetreotide, and Tc
      99m-methylene diphosphonate bone scintigraphy in 30 patients with SDHB-associated
      PGL. Computed tomography (CT) and magnetic resonance imaging (MRI) served as
      standards of reference. RESULTS: Twenty-nine of 30 patients had metastatic
      lesions. In two patients, obvious metastatic lesions on functional imaging were
      missed by CT and MRI. Sensitivity according to patient/body region was 80%/65%
      for 123I-MIBG and 88%/70% for [18F]FDA-PET. False-negative results on 123I-MIBG
      scintigraphy and/or [18F]FDA-PET were not predicted by genotype or biochemical
      phenotype. [18F]FDG-PET yielded a by patient/by body region sensitivity of
      100%/97%. At least 90% of regions that were false negative on 123I-MIBG
      scintigraphy or [18F]FDA-PET were detected by [18F]FDG-PET. In two patients,
      111In-pentetreotide scintigraphy detected liver lesions that were negative on
      other functional imaging modalities. Sensitivities were similar before and after
      chemotherapy or 131I-MIBG treatment, except for a trend toward lower post-
      (60%/41%) versus pretreatment (80%/65%) sensitivity of 123I-MIBG scintigraphy.
      CONCLUSION: With a sensitivity approaching 100%, [18F]FDG-PET is the preferred
      functional imaging modality for staging and treatment monitoring of SDHB-related
      metastatic PGL.

PMID- 17538172
TI  - Perspectives on post-treatment cancer care: qualitative research with survivors,
      nurses, and physicians.
AB  - PURPOSE: Cancer survivors have many medical and psychosocial needs that are
      unaddressed in the post-treatment period. Qualitative research was carried out to
      assess how a survivorship care plan created by oncologists could improve the
      quality of survivorship care. PARTICIPANTS AND METHODS: Focus groups and
      interviews conducted with cancer survivors, nurses, primary care physicians, and
      oncologists provide insights into post-treatment follow-up practices and the
      acceptability and feasibility of providing survivors and referring physicians
      with a cancer survivorship care plan. RESULTS: Cancer survivors reported
      satisfaction with post-treatment medical care, but felt that their psychosocial
      needs were not met. Survivors expressed enthusiastic support for receipt of a
      follow-up care plan. Primary care physicians viewed themselves as playing an
      important role during the post-treatment period and indicated that a written care
      plan for follow-up would help them improve their survivorship practices. Nurses
      recognized the need to improve the care of cancer survivors and suggested that
      they could play an active role in creating and implementing cancer survivorship
      plans. Physicians providing oncology care acknowledged the value of survivorship
      care plans, but were not inclined to complete them because such plans would not
      reduce other reporting and communication requirements and would be burdensome to
      complete given their busy schedules. CONCLUSION: Survivorship care planning is
      viewed favorably by consumers, nurses, and physicians, however there are several
      barriers to its adoption. Barriers may be overcome with: electronic medical
      records, changes in reporting requirements of insurers, advocacy on the part of
      patients, and incorporation of care planning in education and training programs.

PMID- 17538173
TI  - Phase I clinical trial of oxaliplatin in children and adolescents with refractory
      solid tumors.
AB  - PURPOSE: To evaluate the maximum-tolerated dose (MTD), dose-limiting toxicity
      (DLT), pharmacokinetics (PK), and adverse effect profile of oxaliplatin in
      pediatric patients with refractory solid tumors and to determine whether
      carbamazepine reduces oxaliplatin-induced neurotoxicity. PATIENTS AND METHODS:
      Three regimens of oxaliplatin (given intravenously over 2 hours) were tested:
      regimen A (100 mg/m2, 130 mg/m2, or 160 mg/m2 every 3 weeks to determine the MTD
      of oxaliplatin); regimen B (to determine whether carbamazepine starting 24 hours
      before and ending 48 hours after oxaliplatin reduced the dose-limiting
      neurotoxicity and increased the MTD of regimen A); and regimen C (to evaluate the
      safety of a fixed dose two-thirds the MTD of regimen A given every 2 weeks [more
      frequent administration but comparable dose intensity]). RESULTS: Twenty-six
      patients were enrolled on regimens A (n = 11), B (n = 6), and C (n = 9). The DLT
      was grade 3 pharyngolaryngeal dysesthesia, sensory neuropathy, and ataxia at 160
      mg/m2. The MTD was 130 mg/m2 every 3 weeks. At the MTD, the median clearance rate
      of ultrafiltrable platinum was 9.7 L/h/m2 (range, 6.5 to 15.5 L/h/m2). Addition
      of carbamazepine permitted dose escalation to 160 mg/m2 without DLT. DLT was not
      observed with a fixed dose of 85 mg/m2 given every 2 weeks. On all regimens,
      hematologic toxicity was mild. No significant nephrotoxicity, ototoxicity, or
      cumulative neurologic toxicity was observed. CONCLUSION: The DLT, MTD, PK, and
      adverse effect profile of oxaliplatin in pediatric patients with refractory solid
      tumors are similar to those observed in adults. Carbamazepine may reduce the dose
      limiting neurotoxicity of oxaliplatin.

PMID- 17538174
TI  - Whole genome oligonucleotide-based array comparative genomic hybridization
      analysis identified fibroblast growth factor 1 as a prognostic marker for
      advanced-stage serous ovarian adenocarcinomas.
AB  - PURPOSE: To identify markers that can predict overall survival in patients with
      high-grade advanced stage serous adenocarcinomas. PATIENTS AND METHODS:
      Oligonucleotide array comparative genomic hybridization (aCGH) was performed on
      42 microdissected high-grade serous ovarian tumor samples. aCGH segments were
      obtained and a prediction Cox model was built and validated by the standard leave
      one out analysis. Both DNA and mRNA copy numbers of selected genes located on the
      candidate aCGH segments were determined by quantitative polymerase chain reaction
      (qPCR) and quantitative reverse transcriptase PCR (qRT-PCR) analyses. The gene
      that showed the highest correlation was further validated on an independent set
      of specimens and was selected for further functional studies. RESULTS: Two
      chromosomal regions, 4p16.3 and 5q31-5q35.3, exhibited the strongest correlation
      with overall survival (P < .01). From the 5q31 region, fibroblast growth factor 1
      (FGF-1) was selected for further validation study. FGF-1 mRNA copy number was
      significantly correlated with DNA copy number and protein expression levels (P =
      .021 and < .001), and both FGF-1 mRNA and protein levels were significantly
      associated with overall survival (P = .018 and .042). This association was
      validated for protein expression on an independent set of 81 samples, significant
      to P = .006. Further studies showed significant correlation between FGF-1 protein
      expression and CD31+ staining in the tumor stroma (P = .024). Finally, both
      cancer cells and endothelial cells treated with exogenous FGF-1 showed a
      significant increase in cell motility and survival. CONCLUSION: Amplification of
      FGF-1 at 5q31 in ovarian cancer tissues leads to increased angiogenesis, and
      autocrine stimulation of cancer cells, which may result in poorer overall
      survival in patents with high-grade advanced stage serous ovarian cancer.

PMID- 17538175
TI  - Epidermal growth factor receptor variant III status defines clinically distinct
      subtypes of glioblastoma.
AB  - PURPOSE: The clinical significance of epidermal growth factor receptor variant
      III (EGFRvIII) expression in glioblastoma multiforme (GBM) and its relationship
      with other key molecular markers are not clear. We sought to evaluate the
      clinical significance of GBM subtypes as defined by EGFRvIII status. PATIENTS AND
      METHODS: The expression of EGFRvIII was assessed by immunohistochemistry in 649
      patients with newly diagnosed GBM. These data were then examined in conjunction
      with the expression of phospho-intermediates (in a subset of these patients) of
      downstream AKT and Ras pathways and YKL-40 as well as with known clinical risk
      factors, including the Radiation Therapy Oncology Group's recursive partitioning
      analysis (RTOG-RPA) class. RESULTS: The RTOG-RPA class was highly predictive of
      survival in EGFRvIII-negative patients but much less predictive in EGFRvIII
      positive patients. These findings were seen in both an initial test set (n = 268)
      and a larger validation set (n = 381). Similarly, activation of the AKT/MAPK
      pathways and YKL-40 positivity were predictive of poor outcome in EGFRvIII
      negative patients but not in EGFRvIII-positive patients. Pair-wise combinations
      of markers identified EGFRvIII and YKL-40 as prognostically important. In
      particular, outcome in patients with EGFRvIII-negative/YKL-40-negative tumors was
      significantly better than the outcome in patients with the other three
      combinations of these two markers. CONCLUSION: Established prognostic factors in
      GBM were not predictive of outcome in the EGFRvIII-positive subset, although this
      requires confirmation in independent data sets. GBMs negative for both EGFRvIII
      and YKL-40 show less aggressive behavior.

PMID- 17538176
TI  - Chemotherapy delivery issues in central nervous system malignancy: a reality
      check.
AB  - PURPOSE: This review assesses the current state of knowledge regarding
      preclinical and clinical pharmacology for brain tumor chemotherapy and evaluates
      relevant brain tumor pharmacology studies before October 2006. RESULTS:
      Chemotherapeutic regimens in brain tumor therapy have often emerged from
      empirical clinical studies with retrospective pharmacologic explanations, rather
      than prospective trials of rational chemotherapeutic approaches. Brain tumors are
      largely composed of CNS metastases of systemic cancers. Primary brain tumors,
      such as glioblastoma multiforme or primary CNS lymphomas, are less common. Few of
      these tumors have well-defined optimal treatment. Brain tumors are protected from
      systemic chemotherapy by the blood-brain barrier (BBB) and by intrinsic
      properties of the tumors. Pharmacologic studies of delivery of conventional
      chemotherapeutics and novel therapeutics showing actual tumor concentrations and
      biologic effect are lacking. CONCLUSION: In this article, we review drug delivery
      across the BBB, as well as blood-tumor and -cerebrospinal fluid (CSF) barriers,
      and mechanisms to increase drug delivery to CNS and CSF tumors. Because of the
      difficulty in treating CNS tumors, innovative treatments and alternative delivery
      techniques involving brain/cord capillaries, choroid plexus, and CSF are needed.

PMID- 17538177
TI  - Increased permeability of the blood-brain barrier to chemotherapy in metastatic
      brain tumors: establishing a treatment paradigm.
AB  - There is no accepted standard of care for the chemotherapy treatment of
      metastatic brain tumors, which has been generally limited to lipophilic
      alkylators, which may not have efficacy against the tumor that metastasized to
      the brain. More than 50% of chemotherapy agents are natural product drugs, which
      are rarely used in the treatment of metastatic brain tumors because they are
      thought to not cross the blood-brain barrier (BBB). A major protein constituent
      in the BBB is P-glycoprotein (P-gp), which pumps natural product chemotherapy
      drugs and toxins out of the CNS. However, P-gp expression in the neovasculature
      of metastatic brain tumors is similar to the P-gp expression in the
      neovasculature of the primary, extracranial tumor. In contrast, gliomas have
      higher P-gp expression in their neovasculature, similar to the greater intrinsic
      expression of P-gp in normal brain vasculature. This decreased
      immunohistochemical expression of P-gp in the neovasculature of metastatic
      tumors, as well as our recent pharmacologic demonstration of increased tissue
      concentrations of paclitaxel in metastatic brain tumors compared with gliomas,
      support the idea that the choice of chemotherapy agents should be based on the
      histologic origin of the metastatic brain tumor and not on the lipophilicity of
      the drug. Our hypothesis is that metastatic brain tumors from tumors with
      intrinsically low P-gp expression (eg, lung, melanoma, and untreated breast) may
      be more permeable to natural product chemotherapy drugs than gliomas. This
      information could lead to a paradigm shift in the use of natural product drugs
      for metastatic brain tumors.

PMID- 17538178
TI  - Priorities in colorectal cancer research: recommendations from the
      Gastrointestinal Scientific Leadership Council of the Coalition of Cancer
      Cooperative Groups.
AB  - Emerging technologies have greatly expanded our ability to detect, characterize,
      and treat colorectal cancer. The Coalition of Cancer Cooperative Groups convened
      a multidisciplinary panel, the Scientific Leadership Council in GI cancer, to
      discuss and advise on the priorities and opportunities to advance current and
      future approaches into the clinical arena to impact most rapidly the morbidity
      and mortality from this disease. The Council's recommendations for research
      priorities are the result of engagement of community and academic oncologists,
      patient advocacy groups, and other stakeholders including the pharmaceutical
      industry and governmental agencies. We detail some key prospects for
      investigation in the areas of colon cancer detection, prevention, and surgical
      and medical management. Many are in early or definitive clinical trials, and a
      focus on rapid accrual is urged. The implementation of biology-directed
      laboratory investigations, both in association with ongoing clinical trials and
      as a separate developmental strategy for targeted therapies, is supported as the
      route to individualized therapy.

PMID- 17538179
TI  - Addison's disease from non-Hodgkin's lymphoma with normal-size adrenal glands.

PMID- 17538180
TI  - Rosai-Dorfman disease of the epiglottis.

PMID- 17538181
TI  - Blastic transformation of low-grade follicular lymphoma.

PMID- 17538182
TI  - The perception of perception.

PMID- 17538183
TI  - Impact of toxicity assumptions on socioeconomic analysis of breast cancer
      chemotherapy.

PMID- 17538184
TI  - Liposomal doxorubicin and the accelerated approval process.

PMID- 17538185
TI  - Oxalate intake and the risk for nephrolithiasis.
AB  - Most kidney stones consist of calcium oxalate, and higher urinary oxalate
      increases the risk for calcium oxalate nephrolithiasis. However, the relation
      between dietary oxalate and stone risk is unclear. This study prospectively
      examined the relation between oxalate intake and incident nephrolithiasis in the
      Health Professionals Follow-up Study (n = 45,985 men), the Nurses' Health Study I
      (n = 92,872 older women), and the Nurses' Health Study II (n = 101,824 younger
      women). Food frequency questionnaires were used to assess oxalate intake every 4
      yr. Cox proportional hazards regression was used to adjust for age, body mass
      index, thiazide use, and dietary factors. A total of 4605 incident kidney stones
      were documented over a combined 44 yr of follow-up. Mean oxalate intakes were 214
      mg/d in men, 185 mg/d in older women, and 183 mg/d in younger women and were
      similar in stone formers and non-stone formers. Spinach accounted for >40% of
      oxalate intake. For participants in the highest compared with lowest quintile of
      dietary oxalate, the relative risks for stones were 1.22 (95% confidence interval
      [CI] 1.03 to 1.45; P = 0.01 for trend) for men and 1.21 (95% CI 1.01 to 1.44; P =
      0.05 for trend) for older women. Risk was higher in men with lower dietary
      calcium (P = 0.08 for interaction). The relative risks for participants who ate
      eight or more servings of spinach per month compared with fewer than 1 serving
      per month were 1.30 (95% CI 1.08 to 1.58) for men and 1.34 (95% CI 1.10 to 1.64)
      for older women. Oxalate intake and spinach were not associated with risk in
      younger women. These data do not implicate dietary oxalate as a major risk factor
      for nephrolithiasis.

PMID- 17538186
TI  - Role of gp91phox -containing NADPH oxidase in mediating the effect of K
      restriction on ROMK channels and renal K excretion.
AB  - Previous study has demonstrated that superoxide and the related products are
      involved in mediating the effect of low K intake on renal K secretion and ROMK
      channel activity in the cortical collecting duct (CCD). This study investigated
      the role of gp91(phox)-containing NADPH oxidase (NOXII) in mediating the effect
      of low K intake on renal K excretion and ROMK channel activity in gp91(-/-) mice.
      K depletion increased superoxide levels, phosphorylation of c-Jun, expression of
      c-Src, and tyrosine phosphorylation of ROMK in renal cortex and outer medulla in
      wild-type (WT) mice. In contrast, tempol treatment in WT mice abolished whereas
      deletion of gp91 significantly attenuated the effect of low K intake on
      superoxide production, c-Jun phosphorylation, c-Src expression, and tyrosine
      phosphorylation of ROMK. Patch-clamp experiments demonstrated that low K intake
      decreased mean product of channel number (N) and open probability (P) (NP(o)) of
      ROMK channels from 1.1 to 0.4 in the CCD. However, the effect of low K intake on
      ROMK channel activity was significantly attenuated in the CCD from gp91(-/-) mice
      and completely abolished by tempol treatment. Immunocytochemical staining also
      was used to examine the ROMK distribution in WT, gp91(-/-), and WT mice with
      tempol treatment in response to K restriction. K restriction decreased apical
      staining of ROMK in WT mice. In contrast, a sharp apical ROMK staining was
      observed in the tempol-treated WT or gp91(-/-) mice. Metabolic cage study further
      showed that urinary K loss is significantly higher in gp91(-/-) mice than in WT
      mice. It is concluded that superoxide anions play a key role in suppressing K
      secretion during K restriction and that NOXII is involved in mediating the effect
      of low K intake on renal K secretion and ROMK channel activity.

PMID- 17538187
TI  - Chemokine receptor CXCR3 mediates T cell recruitment and tissue injury in
      nephrotoxic nephritis in mice.
AB  - The chemokine receptor CXCR3 is highly expressed on Th1 polarized T cells and has
      been predicted to play an important role in T cell recruitment and immune
      response in a number of inflammatory and autoimmune diseases. For testing whether
      CXCR3 plays a role in renal inflammation, CXCR3-deficient mice were generated and
      nephrotoxic nephritis was induced in C57BL/6 CXCR3(-/-) and C57BL/6 wild-type
      mice. Induction of the nephrotoxic nephritis leads to an increased renal mRNA
      expression of IP-10/CXCL10 (8.6-fold), Mig/CXCL9 (2.3-fold), and I-TAC/CXCL11
      (4.9-fold) during the autologous phase at days 7 and 14. This increased chemokine
      expression was paralleled by the renal infiltration of T cells, followed by renal
      tissue injury, albuminuria, and loss of renal function. Compared with wild-type
      mice, CXCR3-deficient mice had significantly reduced renal T cell infiltrates.
      Moreover, CXCR3(-/-) mice developed less severe nephritis, with significantly
      lower albuminuria, better renal function, and a reduced frequency of glomerular
      crescent formation. Nephritic wild-type and CXCR3(-/-) mice both elicited an
      efficient systemic nephritogenic immune response in terms of antigen-specific IgG
      production and IFN-gamma expression by splenocytes in response to the
      nephritogenic antigen. These findings indicate that the ameliorated nephritis in
      CXCR3-deficient mice is due to impaired renal trafficking of effector T cells
      rather than their inability to mount an efficient humoral or cellular immune
      response. The neutralization of CXCR3 might be a promising therapeutic strategy
      for Th1-dependent inflammatory renal disease.

PMID- 17538188
TI  - Reactive oxygen species in the presence of high glucose alter ureteric bud
      morphogenesis.
AB  - Renal malformations are a major cause of childhood renal failure. During the
      development of the kidney, ureteric bud (UB) branching morphogenesis is critical
      for normal nephrogenesis. These studies investigated whether renal UB branching
      morphogenesis is altered by a high ambient glucose environment and studied
      underlying mechanism(s). Kidney explants that were isolated from different
      periods of gestation (embryonic days 12 to 18) from Hoxb7-green fluorescence
      protein mice were cultured for 24 h in either normal d-glucose (5 mM) or high d
      glucose (25 mM) medium with or without various inhibitors. Alterations in renal
      morphogenesis were assessed by fluorescence microscopy. Paired-homeobox 2 (Pax-2)
      gene expression was determined by real-time quantitative PCR, Western blotting,
      and immunohistology. The results revealed that high d-glucose (25 mM)
      specifically stimulates UB branching morphogenesis via Pax-2 gene expression,
      whereas other glucose analogs, such as d-mannitol, l-glucose, and 2-deoxy-d
      glucose, had no effect. The stimulatory effect of high glucose on UB branching
      was blocked in the presence of catalase and inhibitors of NADPH oxidase,
      mitochondrial electron transport chain complex I, and Akt signaling. Moreover, in
      in vivo studies, it seems that high glucose induces, via Pax-2 (mainly localized
      in UB), acceleration of UB branching but not nephron formation. Taken together,
      these data demonstrate that high glucose alters UB branching morphogenesis. This
      occurs, at least in part, via reactive oxygen species generation, activation of
      Akt signaling, and upregulation of Pax-2 gene expression.

PMID- 17538189
TI  - Regression of nephropathy developed in diabetes by (Pro)renin receptor blockade.
AB  - Activation of prorenin by (pro)renin receptor stimulates the tissue renin
      angiotensin system and plays a significant role in the development of nephropathy
      in diabetic animals. This study examined whether (pro)renin receptor blockade
      inhibits the progression of nephropathy that has already developed in diabetic
      rats. Seventeen-week-old heminephrectomized streptozotocin-induced diabetic rats
      with an increased urinary protein excretion and a significant glomerulosclerosis
      had been treated for 12 wk with the (pro)renin receptor blocker (PRRB),
      angiotensin-converting enzyme inhibitor (ACEi), or vehicle peptide by using
      subcutaneously implanted osmotic minipumps. At the end of observation, in
      diabetic rats that were treated with vehicle, urinary protein excretion was
      progressively increased and a significant progression of glomerulosclerosis was
      observed. In diabetic rats that were treated with PRRB, however, no further
      increase in urinary protein excretion or glomerulosclerosis was observed, but 12
      wk treatment with ACEi only attenuated further increases in urinary protein
      excretion and glomerulosclerosis. The enhanced expression of activated prorenin
      was observed in the kidneys of diabetic rats that were treated with vehicle,
      whereas it was markedly suppressed in the kidneys of diabetic rats that were
      treated with PRRB but not ACEi. These results suggest that (pro)renin receptor
      blockade does not only inhibit the progression of nephropathy but also reverses
      the glomerulosclerosis that has already developed in diabetic rats.

PMID- 17538190
TI  - Serum total bilirubin as a predictive factor for severe neutropenia in lung
      cancer patients treated with cisplatin and irinotecan.
AB  - OBJECTIVE: To clarify the association between pre-treatment total bilirubin (PTB)
      level and severe toxicity in patients receiving cisplatin and irinotecan.
      METHODS: We analyzed retrospectively the relationships of grade 4 neutropenia or
      grade 3-4 diarrhea and clinical variables including PTB and pre-treatment
      neutrophil counts (PNC) using a logistic regression model. RESULTS: One hundred
      and twenty-seven patients (93 men, 34 women; median age: 61 years; range: 24-74
      years) received cisplatin (60 or 80 mg/m2) on day 1 and irinotecan (60 mg/m2) on
      days 1 and 8 every 3 weeks or on days 1, 8 and 15 every 4 weeks. Grade 4
      neutropenia occurred in 29 patients (23%) and grade 3-4 diarrhea occurred in 13
      patients (10%). Grade 4 neutropenia was associated with a higher PTB level (odds
      ratio: 4.9; 95% confidence interval: 1.4-17.7), a higher cisplatin dose (2.8, 1.0
      7.8) and a lower PNC (1.5, 1.0-2.3). Grade 3-4 diarrhea was associated with liver
      metastasis (11.2, 2.2-57.4), a higher cisplatin dose (5.0, 1.2-21.3) and a lower
      PNC (2.0, 1.1-3.6). CONCLUSIONS: PTB level was associated with the severity of
      neutropenia caused by cisplatin and irinotecan.

PMID- 17538191
TI  - Combination chemotherapy with bortezomib, cyclophosphamide and dexamethasone may
      be effective for plasma cell leukemia.
AB  - Plasma cell leukemia is a rare malignant plasma cell disorder characterized by
      proliferation of plasma cells in blood and the bone marrow, the outcome of which
      is poor with conventional therapy. More effective treatment strategies are
      therefore needed for this disorder. Here, we report a case of secondary plasma
      cell leukemia from Immunoglobulin D multiple myeloma refractory to doxorubicin
      containing chemotherapy and thalidomide. The patient achieved complete remission
      with bortezomib-containing chemotherapy as follows: bortezomib 1.3 mg/m2
      intravenous infusion on days 1, 4, 8 and 11; cyclophosphamide 750 mg/m(2)
      intravenous infusion on days 1 and 3; dexamethasone 40 mg/m2 intravenous infusion
      on days 1-4. Complete remission was maintained until the fourth course of the
      treatment, and we then performed autologous peripheral blood stem cell
      transplantation. Our experience suggests that combination chemotherapy with
      bortezomib, cyclophosphamide and dexamethasone may be an effective induction
      treatment for plasma cell leukemia.

PMID- 17538192
TI  - Challenges faced by health workers in implementing the prevention of mother-to
      child HIV transmission (PMTCT) programme in Uganda.
AB  - BACKGROUND: To report the experience of health workers who had played key roles
      in the early stages of implementing the prevention of mother-to-child HIV
      transmission services (PMTCT) in Uganda. METHODS: Interviews were conducted with
      15 key informants including counsellors, obstetricians and PMTCT coordinators at
      the five PMTCT test sites in Uganda to investigate the benefits, challenges and
      sustainability of the PMTCT programme. Audio-taped interviews were held with each
      informant between January and June 2003. These were transcribed verbatim and
      manually analysed using the framework approach. RESULTS: The perceived benefits
      reported by informants were improvement of general obstetric care, provision of
      antiretroviral prophylaxis for HIV-positive mothers, staff training and community
      awareness. The main challenges lay in the reluctance of women to be tested for
      HIV, incomplete follow-up of participants, non-disclosure of HIV status and
      difficulties with infant feeding for HIV-positive mothers. Key informants thought
      that the programme's sustainability depended on maintaining staff morale and
      numbers, on improving services and providing more resources, particularly
      antiretroviral therapy for the HIV-positive women and their families. CONCLUSION:
      Uganda's experience in piloting the PMTCT programme reflected the many challenges
      faced by health workers. Potentially resource-sparing strategies such as the 'opt
      out' approach to HIV testing required further evaluation.

PMID- 17538193
TI  - Psychic tonus, body schema and the parietal lobes: a multiple lesion case
      analysis.
AB  - The psychic tonus model (Braun and colleagues, 1999, 2002, 2003, 2006) states
      that the left hemisphere is a "booster" of internal experience and behavior in
      general, and that the right hemisphere is a "dampener". Twenty-five patients with
      a "positive" extreme disturbance of body schema (somatoparaphrenia) and 37
      patients with a "negative" disturbance of body schema (autotopagnosia or
      Gerstmann's syndrome), all following a unilateral parietal lesion, were found in
      the literature and were analyzed to test predictions from Braun's "psychic tonus"
      model. As expected, patients with a positive syndrome had a right hemisphere
      lesion significantly more frequently, and those with a negative syndrome had a
      left hemisphere lesion significantly more frequently. Thus the psychic tonus
      model of hemispheric specialization, previously supported with regard to
      psychomotor baseline, libido, talkativeness, memory, auditory and visual
      perceptual tonus, now incorporates the tonus of representation of the body (body
      schema) in the parietal lobes.

PMID- 17538194
TI  - Perceived behavioral changes in early multiple sclerosis.
AB  - Acquired behavioral changes have essentially been described in advanced multiple
      sclerosis (MS). The present study was designed to determine whether behavioral
      modifications specifically related to the MS pathological process could be
      identified in the initial phase of the disease, as compared to control patients
      with chronic, relapsing and progressive inflammatory disorders not involving the
      central nervous system (CNS). Eighty-eight early MS patients (Expanded Disability
      Status Scale score <or= 2.5) and 48 controls were tested. Perceived changes by
      informants in behavioral control, goal-directed behavior, decision making,
      emotional expression, insight and interpersonal relationships were assessed using
      the Iowa Scale of Personality Change (ISPC). Executive behavioral disturbances
      were screened using the Dysexecutive Questionnaire (DEX). The mean change between
      the premorbid and postmorbid ISPC ratings was similar in the MS [12.2 (SD 15.6)]
      and in the control [11.5 (SD 15.1)] group. The perceived behavioral changes
      (PBCs) most frequently reported in both groups were lack of stamina,
      lability/moodiness, anxiety, vulnerability to stress and irritability.
      Pathological scores in the DEX were also similar in both groups. Correlations
      between PBCs and DEX scores were different in MS and control groups. MS patients
      with cognitive impairment had a marginally higher number of PBCs than control
      patients (p=0.056) and a significantly higher DEXp score (p=0.04). These results
      suggest that (1) PBCs occurring in early MS patients were not different from
      those induced by comparable chronic non-CNS disorders, (2) qualitative
      differences in the relationship between behavioral symptoms and executive
      behavioral changes may exist between MS and control groups, and (3) behavioral
      symptoms seem associated with cognitive deficits in MS. We further plan to assess
      these observations longitudinally.

PMID- 17538195
TI  - Intransigent vowel-consonant position in Korean dysgraphia: evidence of spatial
      constructive representation.
AB  - Dysgraphia due to a focal brain lesion can be characterized by substitution,
      transposition, deletion and/or addition errors of graphemes or strokes. However,
      those linguistic errors can be language-specific because the writing system of a
      given language may influence error patterns. We investigated a Korean stroke
      patient, a 57-year-old English teacher with dysgraphia both in Korean Han-geul
      [see text] and in English alphabet writings. The results of an experimental
      testing revealed transposition errors between a consonant and a vowel only in
      English but not in Korean writings. This austerity of vowel-consonant position
      may be attributed to a unique Korean writing system of a spatially well-formed
      syllabic configuration or block with consonant(s) and a vowel. In light of a
      neuropsychological model of writing, which depicts a multi-level spelling and
      writing process, we suggest a spatial-constructional component of internal
      orthographic representations in Korean writing. This Korean graphemic
      configuration feature may be resistant to a focal, left cerebral damage, and
      thus, we also discuss our results in terms of cerebral lateralization of the
      writing processes.

PMID- 17538196
TI  - Parietal dysgraphia: characterization of abnormal writing stroke sequences,
      character formation and character recall.
AB  - OBJECTIVE: To characterize various dysgraphic symptoms in parietal agraphia.
      METHOD: We examined the writing impairments of four dysgraphia patients from
      parietal lobe lesions using a special writing test with 100 character kanji
      (Japanese morphograms) and their kana (Japanese phonetic writing) transcriptions,
      and related the test performance to a lesion site. RESULTS: Patients 1 and 2 had
      postcentral gyrus lesions and showed character distortion and tactile agnosia,
      with patient 1 also having limb apraxia. Patients 3 and 4 had superior parietal
      lobule lesions and features characteristic of apraxic agraphia (grapheme
      deformity and a writing stroke sequence disorder) and character imagery deficits
      (impaired character recall). Agraphia with impaired character recall and abnormal
      grapheme formation were more pronounced in patient 4, in whom the lesion extended
      to the inferior parietal, superior occipital and precuneus gyri. CONCLUSION: The
      present findings and a review of the literature suggest that: (i) a postcentral
      gyrus lesion can yield graphemic distortion (somesthetic dysgraphia), (ii)
      abnormal grapheme formation and impaired character recall are associated with
      lesions surrounding the intraparietal sulcus, the symptom being more severe with
      the involvement of the inferior parietal, superior occipital and precuneus gyri,
      (iii) disordered writing stroke sequences are caused by a damaged anterior
      intraparietal area.

PMID- 17538197
TI  - Activation of brain attention systems in individuals with symptoms of ADHD.
AB  - Previous research investigating attention and impulse control in individuals with
      Attention-Deficit/Hyperactivity Disorder (ADHD) has largely ignored the
      symptomatic differences among the three subtypes of ADHD: ADHD-Inattentive Type,
      ADHD-Hyperactive/Impulsive Type, and ADHD-Combined Type. The present study
      examined attention and impulse control by focusing on these subtypes. Based on
      their self-reported symptoms of ADHD, participants belonged to one of four
      groups: ADHD-Inattentive, ADHD-Hyperactive/Impulsive, ADHD-Combined, and control.
      Cortical activity was recorded from participants during performance of a Go/NoGo
      task. The event-related potentials (ERP) measured at frontal and posterior sites
      discriminated between the control group and participants with symptoms of ADHD.
      The control group consistently exhibited a higher P3 amplitude than all the ADHD
      groups. The main difference occurred at the frontal site, indicating that
      individuals with ADHD symptoms have deficits in the anterior attentional system,
      which mediates signal detection. Behavioral measures of signal sensitivity
      revealed that the ADHD-Inattentive and the ADHD-Hyperactive/Impulsive groups had
      more difficulty with the attention-demanding Go/NoGo respond-to-target task,
      while behavioral measures of response bias indicated that the ADHD
      Hyperactive/Impulsive and the ADHD-Combined groups responded more liberally in
      the inhibition-demanding Go/NoGo suppress-to-target task.

PMID- 17538198
TI  - Neuropsychological findings of extrapontine myelinolysis without central pontine
      myelinolysis.
AB  - Central pontine myelinolysis (CPM) and extrapontine myelinolysis (EPM) are well
      recognized syndromes related to the rapid correction of hyponatremia, which are
      reported to show brain stem signs and various movement disorders. Cognitive
      dysfunction and neuropsychological findings, however, have seldom been reported.
      Cognitive manifestations in osmotic myelinolysis may have been underestimated due
      to the prominent brain stem symptoms and movement disorders. We report a case of
      EPM without CPM and describe the neuropsychological findings of EPM. The absence
      of CPM in this case made it possible to test neuropsychological function in the
      acute stage. Neuropsychological testing showed severe impairment of attention,
      verbal and visual memory, visuospatial function, and frontal/executive function.
      Language and language-related functions were normal except naming.

PMID- 17538199
TI  - Rheological properties of synovial fluids.
AB  - Synovial fluid is the joint lubricant and shock absorber [Semin. Arthritis Rheum.
      32 (2002), 10-37] as well as the source of nutrition for articular cartilage. The
      purpose of the present paper is to provide a comprehensive review of the
      rheological properties of synovial fluid as they relate to its chemical
      composition. Given its importance in the rheology of synovial fluid, an overview
      of the structure and rheology of HA (hyaluronic acid) is presented first. The
      rheology of synovial fluids is discussed in detail, with a focus on the possible
      diagnosis of joint pathology based on the observed differences in rheological
      parameters and trends. The deterioration of viscoelastic properties of synovial
      fluid in pathological states due to effects of HA concentration and molecular
      weight is further described. Recent findings pertaining to the composition and
      rheology of periprosthetic fluid, the fluid that bathes prosthetic joints in vivo
      are reported.

PMID- 17538200
TI  - Remodelling of the zero-stress state and residual strains in apoE-deficient mouse
      aorta.
AB  - Atherosclerosis is the most frequent cause of death and severe chronic disability
      in North America and Europe. The atherosclerosis-prone apolipoprotein E (apoE)
      deficient mice contain the entire spectrum of lesions observed during
      atherogenesis. Significant remodelling of the artery occurs in atherosclerosis.
      The aim was to study the remodelling of the zero-stress state of the aorta in
      apoE-deficient mice up to 56 weeks of age. Normal wild-type mice served as
      control groups. The mice were euthanised at ages 10, 28 and 56 weeks and tissue
      rings where excised from several locations along the aorta. The rings where
      photographed in the no-load state (without any external forces applied), then cut
      radially to obtain the zero-stress state and photographed again. The cross
      sectional wall area and wall thickness increased over time in apoE-deficient mice
      compared to controls (P<0.001). The residual strains at the inner and outer
      surface varied as function of aortic location both in controls and apoE-deficient
      mice (P<0.001). From age 28 to age 56 weeks a gradual increase in positive strain
      at the outer surface and negative strain at the inner surface was found in the
      apoE-deficient mice when compared to age-matched control mice (P<0.001).
      Furthermore, the inner residual strain in the plaque location was significantly
      smaller than in the non-plaque location in the rings with atherosclerotic plaques
      (P<0.001). The change over time of the opening angle was especially pronounced in
      the aortic arch. The opening angle increased to app. 200 degrees in the aortic
      arch in apoE-deficient mice at 56 weeks of age whereas it in age-matched controls
      was app. 125 degrees. Correspondingly, atherosclerotic plaques were prominent in
      the apoE-deficient mice, especially at week 56 in the ascending aorta and the
      aortic arch. In conclusion, a pronounced remodelling of the biomechanical
      properties in aorta was found in apoE-deficient mice. The stress gradient across
      the vessel wall in the plaque region is likely larger in vivo due to the smaller
      residual strain in the plaque area.

PMID- 17538201
TI  - Developed pulsatile flow in a deployed coronary stent.
AB  - The patho-physiologic process of restenosis and tissue growth may not be
      completely eliminated and is the primary concern of clinicians performing
      angioplasty and stent implantation procedures. Recent evidence suggests that the
      restenosis process is influenced by several factors: (1) geometry and size of
      vessel; (2) stent design; and (3) it's location that alter hemodynamic
      parameters, including local wall shear stress (WSS) distributions. The present
      three-dimensional (3D) analysis of pulsatile flow in a deployed coronary stent:
      (1) shows complex 3D variation of hemodynamic parameters; and (2) quantifies the
      changes in local WSS distributions for developed flow and compares with recently
      published WSS data for developing flow. Higher order of magnitude of WSS of 290
      dyn/cm(2) is observed on the surface of cross-link intersections at the entrance
      of the stent for developed flow, which is about half of that for developing flow.
      Low WSS of 0.8 dyn/cm(2) and negative WSS of -8 dyn/cm(2) are seen at the
      immediate upstream and downstream regions of strut intersections. Persistent
      recirculation is observed at the downstream region of each strut cross-link and
      the regions of low and negative WSS may lead to patho-physiologic conditions near
      the stented region. The key finding of this study is that the location of stent
      in the coronary artery determines the developing or developed nature of the flow,
      which in turn, results in varied level of WSS.

PMID- 17538202
TI  - Hemodynamic simulation in a novel design for femoral bypass grafts.
AB  - The effectiveness of femoral bypass grafts is correlated with the geometric
      configuration and hemodynamics of the bypass and the arteries. As an attempt to
      develop a new design for femoral bypass grafts, we present a novel geometric
      configuration for a symmetrically implanted 2-way bypass graft. In order to
      investigate how the symmetric 2-way bypass grafts affect the flow patterns
      through the anastomosis, physiologic blood flows in 1-way and 2-way models for a
      fully stenosed femoral bypass were simulated with the finite element method, and
      the hemodynamic factors in these models were studied. The temporal and spatial
      distributions of flow patterns and wall shear stresses in the vicinity of distal
      anastomosis during the cardiac cycle were analyzed. The results computed showed
      that the 2-way model has more preferable hemodynamics than the 1-way model in the
      distribution of flow patterns and wall shear stresses, and it may improve the
      flow conditions and decrease the probability of restenosis. However, the
      limitations of the 2-way bypass model may counteract the positive effects. More
      detailed hemodynamic studies are necessary to fully assess the viability of the 2
      way bypass graft.

PMID- 17538203
TI  - Peristaltic flow of a couple stress fluid in an asymmetric channel.
AB  - This paper presents an analysis of the peristaltic flow of a couple stress fluid
      in an asymmetric channel. The asymmetric nature of the flow is introduced through
      the peristaltic waves of different amplitudes and phases on the channel walls.
      Mathematical modelling corresponding to a two-dimensional flow has been carried
      out. The flow analysis is presented under long wavelength and low Reynolds number
      approximations. Closed form solutions for the axial velocity, stream function and
      the axial pressure gradient are given. Numerical computations have been carried
      out for the pressure rise per wavelength, friction forces and trapping. It is
      noted that there is a decrease in the pressure when the couple stress fluid
      parameter increases. The variation of the couple stress fluid parameter with the
      size of the trapped bolus is also similar to that of pressure. Furthermore, the
      friction force on the lower channel wall is greater than that on the upper
      channel wall.

PMID- 17538204
TI  - Asymmetric gene expression in the brain during acute compensation to unilateral
      vestibular labyrinthectomy in the Mongolian gerbil.
AB  - Commercial microarrays were used to identify transcriptome expression within
      vestibular related brain regions (vestibular brainstem and cerebellum, and
      caudotemporal cortical regions) during the acute period of recovery following
      unilateral surgical vestibular labyrinth ablation in the gerbil. As a
      representative model of vestibular compensation, vestibular lesions in the gerbil
      produced activation in a common set of genes related to vestibular compensation.
      The total RNA was prepared and amplified using Affymetrix Gene Chip probes from
      the Rat U34 Neurobiology and R230, and Mouse M430 gene sets, resulting in GCRMA
      summarized data from S+AA software. Matched rat and mouse genes from gerbil
      hybridization produced good interspecies synteny. Multiple gene target trends
      supported global increases in neuron excitability throughout the vestibular
      brainstem and cerebellum. We focused further on gene expression with anatomically
      asymmetric activation relative to the lesion, indicative of involvement in
      rebalancing central vestibular tone during the vestibular compensation process.
      Cluster analysis revealed distinct spatial (regional and ipsi-contra) and
      temporal patterns. The asymmetric genes were part of well-defined neuron-related
      networks and included multiple members of the glutamate and GABA neurotransmitter
      systems. Transcripts for D3 dopamine, glycine, and some GABA receptor signals
      increased quickly in the ipsilesional vestibular complex and then increased
      gradually in the contralateral region, restoring the expression symmetry.
      Alternatively, the NMDA binding subunit decreased gradually over the acute
      compensation period in the contralateral vestibular complex. There was evidence
      for numerous associations between signaling systems with PKC as one possible
      mediator between early changes in GABA and progressive changes in NMDA signaling.
      These data begin to define the compensatory response at the level of molecular
      cascades.

PMID- 17538205
TI  - Unilateral labyrinthectomy induced changes on GDNF receptor complex proteins in
      the rat medial vestibular nuclei.
AB  - In the auditory periphery, GDNF has been shown to have a trophic effect to spiral
      ganglion neurons, both during development and in adult animals. We have studied
      the effect of unilateral labyrinthectomy (UL) on protein levels and expression of
      GDNF multicomponent receptor complex: the ret tyrosine kinase and coreceptor
      GFRalpha-1 in the medial vestibular nucleus of the adult rat. GFRalpha-1 protein
      levels display an increasing trend in ipsilateral medial vestibular nucleus
      culminating at 48 h post UL. On the other hand, GFRalpha-1 mRNA expression levels
      in ipsi- and contralateral medial vestibular nucleus show a steadily decreasing
      trend that is significant at 1 week post-lesion. Protein levels for c-Ret
      isoforms also show an initial bilateral decreasing trend that ceases at 48 h in
      ipsilateral medial vestibular nucleus but persists on the contralateral side. c
      Ret mRNA expression levels show a significant decrease at 4 h post UL followed by
      another significant decrease 1 week post UL. Our data would suggest that
      neurotrophins belonging to the GDNF family are involved in this model of post
      lesional CNS plasticity.

PMID- 17538207
TI  - Does the method of sternocleidomastoid muscle activation affect the vestibular
      evoked myogenic potential response?
AB  - The objective of this study was to assess the effects of different methods of
      sternocleidomastoid muscle (SCM) activation on vestibular evoked myogenic
      potentials (VEMP). Forty normal volunteers were tested using three different
      methods of SCM activation: sitting with the head turned away from the test ear
      (SIT), supine with the head held straight up (SHU), and supine with the head held
      up and turned away from the test ear (SHT). Dependent measures were latency, and
      amplitude. Head and body position significantly affected the amplitude of the
      VEMP, but had no significant effect on latency. Testing subjects in the supine
      position with the head up and turned toward the non-test ear yielded the most
      robust amplitude response and sternocleidomastoid EMG activity. When amplitude
      measures where corrected according to tonic electromyographic (EMG) activity no
      significant difference was noted between the three different test positions. The
      increased amplitude in the supine with head turned position can be directly
      attributed to increased tonic SCM EMG activity.

PMID- 17538206
TI  - A critical period for the impact of vestibular sensation on ferret motor
      development.
AB  - Children with hearing deficits and hypofunctioning vestibular receptors
      frequently have delayed motor development. This study focuses on when the
      vestibular system needs to be active for normal motor behavior development and
      the maturation of the soleus muscle in the ferret. Both vestibular labyrinths
      were removed from ferrets at Postnatal day 10 (P10), P21, or P45 and the
      resulting data were compared with ferrets that had undergone a sham surgery at
      the same ages. The animals were sacrificed at P120 (young adult ferret). The
      resulting data from these ferrets revealed that standing and walking balance was
      significantly affected when the vestibular system was eliminated at or before
      P21. The soleus of P10 and P21 animals generally had smaller diameter muscle
      fibers and proportionally less type I Myosin Heavy Chain (MHC) and more type IIX
      MHC. The twitch contraction time of the soleus of the P21 group was significantly
      slower than the other groups. It appears that the vestibular system is important
      to motor and muscle fiber development in the ferret during the period before P21.
      The eyes are still closed at that age and all of the vestibular receptors are not
      fully mature. These findings imply a "critical period" for vestibular sensation
      and the development of a muscle that is important to standing balance.

PMID- 17538208
TI  - The effect of alcohol ingestion on ocular counterrolling.
AB  - Nineteen normal subjects underwent two naso-occipital rotations to 90 degrees
      right and left ear down in our standard ocular counterrolling (OCR) protocol.
      Both eyes were videotaped. Following two rotations, subjects drank 90 ml vodka in
      180 ml orange juice; and in about 20 min, when blood alcohol levels reached 0.04
      0.09%, the protocol was repeated. An SMI videooculography system provided
      measurements. Results showed that amplitude of OCR was significantly decreased
      after alcohol ingestion; smoothness was significantly increased after alcohol,
      similar to alcohol's effect on essential tremor. Although disconjugacy was not
      significantly different in the two conditions when the entire trials were
      examined, the latter portions of the post-alcohol trials did show significant
      disconjugacy, similar to earlier findings in vestibular-defective patients whose
      OCR deficits were apparent only in the final segments of the rotation trials. We
      postulate the results are due to alcohol's action on cerebellar GABAergic
      Purkinje cells projecting to vestibular nuclei.

PMID- 17538209
TI  - Spatial orientation of periodic alternating drift (PAD).
AB  - Sinusoidal vestibular stimulation induces in the intact rabbit in prone position
      a periodic alternating drift (PAD), evident in the earth horizontal plane when
      the animal is rotated about the vertical axis but weak in the vertical one when
      the animal is rotated about the longitudinal axis. It has been hypothesized that
      these oscillations are related to an intrinsic instability of the velocity
      storage, due to the length of its time constant. The velocity storage has the
      longest time constant aligned with the vertical axis, and it changes its
      orientation with the gravity vector. The present research examined the spatial
      orientation of PAD in relation to changes of the animal position with respect to
      gravity. Normal pigmented rabbits were sinusoidally oscillated about their
      longitudinal axes to evoke vertical eye responses. The stimulation was carried
      out with the animal in prone position and with the animal in nose-up condition.
      With the animal in prone position, PAD had a weak vertical component, but an
      evident horizontal component was visible. When the animal was in nose-up
      position, the horizontal component of PAD was clearly visible, while the vertical
      component was negligible. In both stimulation conditions PAD period and peak
      velocity were not modulated by the stimulus characteristics. These results are
      consistent with a model of PAD based on an interaction between velocity storage
      and the cerebellar adaptation-habituation circuit.

PMID- 17538210
TI  - Vestibulo-ocular function in anxiety disorders.
AB  - Previous studies of vestibulo-ocular function in patients with anxiety disorders
      have suggested a higher prevalence of peripheral vestibular dysfunction compared
      to control populations, especially in panic disorder with agoraphobia. Also, our
      recent companion studies have indicated abnormalities in postural control in
      patients with anxiety disorders who report a high degree of space and motion
      discomfort. The aim of the present study was to assess the VOR, including the
      semicircular canal-ocular reflex, the otolith-ocular reflex, and semicircular
      canal-otolith interaction, in a well-defined group of patients with anxiety
      disorders. The study included 72 patients with anxiety disorders (age 30.6 +/-
      10.6 yrs; 60 (83.3% F) and 29 psychiatrically normal controls (age 35.0 +/minus;
      11.6 yrs; 24 (82.8% F). 25 patients had panic disorder; 47 patients had non-panic
      anxiety. Patients were further categorized based on the presence (45 of 72) or
      absence (27 of 72) of height phobia and the presence (27 of 72) or absence (45 of
      72) of excessive space and motion discomfort (SMD). Sinusoidal and constant
      velocity earth-vertical axis rotation (EVAR) was used to assess the semicircular
      canal-ocular reflex. Constant velocity off-vertical axis rotation (OVAR) was used
      to assess both the otolith-ocular reflex and static semicircular canal-otolith
      interaction. Sinusoidal OVAR was used to assess dynamic semicircular canal
      otolith interaction. The eye movement response to rotation was measured using
      bitemporal electro-oculography. Results showed a significantly higher VOR gain
      and a significantly shorter VOR time constant in anxiety patients. The effect of
      anxiety on VOR gain was significantly greater in patients without SMD as compared
      to those with SMD. Anxiety patients without height phobia had a larger OVAR
      modulation. We postulate that in patients with anxiety, there is increased
      vestibular sensitivity and impaired velocity storage. Excessive SMD and height
      phobia seem to have a mitigating effect on abnormal vestibular sensitivity,
      possibly via a down-weighting of central vestibular pathways.

PMID- 17538211
TI  - The lesion site of vestibular dysfunction in Ramsay Hunt syndrome: a study by
      click and galvanic VEMP.
AB  - Ramsay Hunt syndrome (RHS) is characterized by vestibulocochlear dysfunction in
      addition to facial paralysis and auricular vesicles. The present study
      investigated the lesion site of vestibular dysfunction in a group of 10 RHS
      patients. Caloric testing, vestibular evoked myogenic potentials by click sound
      (cVEMP) and by galvanic stimulation (gVEMP) were used to assess the function of
      the lateral semicircular canal, saccule, and their afferents. The results of
      caloric testing (all 10 cases showed canal paresis) mean the existence of lesion
      sites in lateral semicircular canal and/or superior vestibular nerve (SVN).
      Abnormal cVEMPs in 7 patients mean the existence of lesions in saccule and/or
      inferior vestibular nerve (IVN). Four of the 6 patients with absent cVEMP also
      underwent gVEMP. The results of gVEMP (2 absent and 2 normal) mean that the
      former 2 have lesions of the vestibular nerve, and the latter 2 have only
      saccular lesions concerning the pathway of VEMPs. Thus, our study suggested that
      lesion sites of vestibular symptoms in RHS could be in the vestibular nerve
      and/or labyrinth, and in SVN and/or IVN. In other words, in the light of
      vestibular symptoms, there is the diversity of lesion sites.

PMID- 17538212
TI  - The assessment of increased sensitivity to visual stimuli in patients with
      chronic dizziness.
AB  - Patients with chronic vestibular dysfunction often experience visually-induced
      aggravation of dizzy symptoms (visual vertigo; VV). The Situational
      Characteristics Questionnaire (SCQ), Computerized Dynamic Posturography or Rod
      and Frame Test (RFT) are used to assess VV symptoms. This study evaluates whether
      correlations exist between these three tests, their ability to identify patients
      with VV and whether emotional state correlates with VV symptoms. Tests were
      completed by 20 normal controls (Group NC), 20 patients with vestibular
      dysfunction plus VV (Group VV) and 13 without VV (Group NVV). Additionally, the
      Vertigo Symptom Scale (VSS-V) was applied to quantify general, non-visually
      induced vertigo (dizziness, lightheadedness and/or spinning) and imbalance.
      Autonomic (VSS-A) and psychological symptoms (Hospital Anxiety and Depression
      questionnaire; HAD) were also assessed. With the SCQ 100% of Group VV scored
      outside normal ranges and scores differed significantly between Group VV and both
      Groups NC and NVV. RFT values were not significantly different between groups;
      only 15% of patients scored outside normal ranges. Posturography scores were
      abnormal for 50% of patients; significant differences were noted between Groups
      NC and VV for composite scores and ratios 3/1, 4/1, 5/1 and 6/1 (indicative of
      abnormal sensory re-weighting). There were no correlations between the three data
      sets in patients. Anxiety and depression scores significantly differed between
      Groups NC and VV but not between patient groups; this indicates that
      psychological symptoms may be present in either patient group. The SCQ can be
      used to corroborate an initial clinical diagnosis of VV and quantify its severity
      in patients with vestibular dysfunction. Posturography data suggested patients
      with VV have a sensory re-weighting abnormality. The rod and frame test results
      and posturography findings agree less with the clinical diagnosis of VV.
      Psychological symptoms may need to be addressed.

PMID- 17538213
TI  - The five times sit to stand test: responsiveness to change and concurrent
      validity in adults undergoing vestibular rehabilitation.
AB  - OBJECTIVE: The purpose of this study was to determine if patients with balance
      and vestibular disorders would demonstrate clinically meaningful improvement in
      the Five Times Sit to Stand Test (FTSST) score as a result of vestibular
      rehabilitation and to determine the concurrent validity of the FTSST. DESIGN:
      Retrospective chart review of 351 people who underwent individualized outpatient
      vestibular rehabilitation programs. SETTING: Outpatient tertiary balance and
      vestibular clinic. SUBJECTS: One hundred and seventeen patients (45 men, 72
      women), mean age 62.7 years, with peripheral, central or mixed vestibular
      dysfunction. MAIN OUTCOME MEASURES: FTSST, gait speed, Timed Up and Go Test
      (TUG), Dynamic Gait Index (DGI), Dizziness Handicap Inventory (DHI), and
      Activities-Specific Balance Confidence Scale (ABC). RESULTS: The mean change in
      FTSST score was 2.7 seconds. Subjects demonstrated statistically significant
      improvements in the FTSST, gait speed, ABC, DHI, DGI and TUG after vestibular
      rehabilitation (p < 0.01). The responsiveness-treatment coefficient (RT) was
      calculated as 0.58 for the FTSST indicating moderate responsiveness. Logistic
      regression showed that an improvement in the FTSST of greater than 2.3 seconds
      resulted in an odds ratio of 4.67 for demonstrating clinical improvement in DHI,
      compared with a change less than 2.3 seconds. The univariate linear regression
      model for baseline FTSST predicting FTSST change was significant (p < 0.01) and
      predicted 49% of the change variance. The FTSST scores demonstrated a moderate
      correlation with gait speed and the TUG (p< 0.01). FTSST improvement subsequent
      to vestibular rehabilitation was moderately correlated with improvements in the
      DGI and the TUG scores (p< 0.01). CONCLUSIONS: The FTSST was moderately
      responsive to change over time and was moderately related to measures of gait and
      dynamic balance.

PMID- 17538215
TI  - [Cost minimization/effectiveness/benefit analysis].

PMID- 17538214
TI  - [Radiological diagnosis of gastric cancer: double contrast method].

PMID- 17538216
TI  - [SPECT imaging for clinical use].

PMID- 17538217
TI  - [Constitution on health and medical matters].

PMID- 17538218
TI  - [Performance evaluation for CT-AEC(CT automatic exposure control)systems].
AB  - Although many current CT scanners incorporate CT-AEC, performance evaluation is
      not standardized. This study evaluates the performance of the latest CT-AEC of
      each manufacturer with the aim of establishing a standard CT-AEC performance
      evaluation method. The design of the phantoms was based upon the operation
      characteristics of different CT-AECs. A cone, an ellipse, a variable-shaped
      ellipse, stepped phantoms, and their analysis software were devised and carried
      out the field test. The targets were LightSpeed VCT 64 with 2D and 3D Auto
      mA(GE), Aquilion 64M with Real-EC and Volume-EC(Toshiba), Sensation 64 with CARE
      Dose and CARE Dose 4D(Siemens), and Bulliance 16P with Dose Right(Philips). Data
      was acquired while varying the typical abdominal CT(with CT-AEC)scanning
      conditions (120 kV, 5 mm slice, standard function for abdomen, scanning range 200
      mm). The acquired images were converted to the DICOM format and image noise(SD)
      was calculated using dedicated software. All 4 CT-AECs reduced exposure dose. For
      GE and Toshiba, image noise was constant and met the target. For Siemens, noise
      was independent of phantom shape but varied uniformly with phantom size. For
      Philips, noise varied with phantom size and shape, and variation degree depended
      on phantom thickness in scanogram direction. The results reflect the basic
      concept and performance characteristics of the methods. Standardization of CT-AEC
      performance evaluation is possible using these phantoms.

PMID- 17538219
TI  - [Three corporate, joint decisions "guideline to manage quality of safety in the
      technical part of the department of radiology"].

PMID- 17538221
TI  - [The international activity of JIRA international division: investigation into
      medical device-related regulations in Korea].

PMID- 17538222
TI  - [Development and assessment of an automatic quantitative cerebral vascular
      reserve estimation tool for use with triple-injection 99mTc-ECD SPECT].
AB  - In nuclear medicine, cerebral vascular reserve(CVR) is evaluated using technetium
      99m ethyl cysteinate dimer [99mTc-ECD] and acetazolamide(ACZ). We developed a
      protocol involving the intravenous injection of 99mTc-ECD in three divided
      doses(TIE method), and have found that the cerebrovascular response to ACZ
      depended on time after ACZ administration. However, it was difficult to obtain
      high-precision quantitative SPECT images by the conventional method because of
      complicated image processing and image degradation accompanying image
      subtraction. We recently developed software known as the Automatic Quantitative
      CVR Estimation Tool(hereinafter referred to as Triple AQCEL), which, after the
      input of simple parameters, enables us to carry out automatic reconstruction of
      quantitative SPECT images without image degradation due to subtraction. Triple
      AQCEL was determined to reduce image degradation caused by subtraction and to
      provide valid quantitative data. Because Triple AQCEL does not require manual
      determination of ROI or image selection for the reconstruction of quantitative
      SPECT images, reproducibility of regional cerebral blood flow by 3DSRT is
      ensured. Since all analyses in evaluation by the TIE method are automated and the
      operator plays no part in them, with the resulting increase of throughput, this
      software will contribute to improved reproducibility of regional cerebral blood
      flow data, and will be useful in clinical pathophysiological assessment both
      preoperatively and during postoperative follow-up.

PMID- 17538223
TI  - [Movement analysis of chest MR image under rest breath using realignment of SPM].
AB  - Analyses of diaphragm and chest wall motion are good indicators to evaluate
      clinical status and pulmonary function before and after surgery for respiratory
      disease. Noninvasive MR images using fast gradient recalled echo techniques
      recently have received a great deal of attention for their assessment of
      inspiratory motion. However, it is laborious to analyze a large number of dynamic
      MR images. Therefore, we performed movement analyses of chest 2D MR images by
      using the public domain software statistical parametric mapping(SPM)Realignment
      sub-routine, which is commonly used for the motion correction of brain functional
      MRI analyses. First, dynamic 2D MR images of a glue-stick phantom were measured
      as a simple reciprocal movement model and were numerically analyzed by the SPM
      Realignment. The resulting translation to each axis coincided with the measured
      values. Then the dynamic images of normal volunteers under free breathing were
      analyzed by the same method, and we found that the inspiratory motions were
      quantitatively shown as the translation to each axis. These results revealed that
      the SPM Realignment is a useful tool for screening the magnitude and
      characteristics of inspiratory motion.

PMID- 17538224
TI  - [Examination of scan parameters that influence image quality in three-dimensional
      rotational angiography(3D-RA)].
AB  - Because the imaging qualities of three-dimensional rotational angiography(3D
      RA)are influenced by various imaging parameters, it is difficult to obtain high
      quality images from 3D-RA. In this study, we compared two methods of 3D-RA, the
      propeller rotation technique(PRT)and the roll rotation technique(RRT)by changing
      image intensifier(I.I.)sizes(5, 7 and 9 inches)using a test chart and handmade
      phantom. The results of this study demonstrated that one of the factors
      determining the image quality of 3D-RA was spatial resolution. Therefore, it was
      important to choose an optimum I.I. size that was similar in size to collimating
      the region of interest(ROI)in clinical use. Another factor influencing image
      quality was radiographic condition, especially the setting of tube voltage. This
      factor was indispensable in obtaining good image contrast, but the use of high
      voltage exposure was one of the reasons for lower image contrast. Therefore, if
      image contrast was insufficient, the image qualities of 3D-RA became worse with
      increasing tube voltage because the tube voltage in this study was automatically
      changed according to scanning method and I.I. size. In addition, because the
      spatial resolution of PRT was similar to that of RRT, we thought it better to use
      PRT because the data acquisition time(scan time)of this technique was 4 seconds
      shorter than that of RRT, whereas, if PRT was used, it was necessary to set a
      suitable rate of injection of contrast medium because the setting of the tube
      voltage of PRT was 10 kV higher than that of RRT. In conclusion, to improve the
      image qualities of 3D-RA, we considered it necessary to obtain sufficient image
      contrast not influenced by high tube voltage and to choose an optimum I.I. size
      suitable for the spatial resolution of ROI.

PMID- 17538225
TI  - [Examination of patient skin dose during abdominal interventional radiology using
      a GAF system].
AB  - Radiation-induced skin injury caused by interventional radiology(IVR)is a
      deterministic effect. If exposure dose exceeds threshold dose, injuries may
      occur. It therefore is important to understand the maximum exposure dose in skin.
      The purpose of this study was to determine the maximum exposure dose and its dose
      distribution. Moreover, to analyze the factors from measuring the absorbed dose
      in the incoming radiation side, a film-type dosimeter was used. When the measured
      results were determined in terms of the clinical aspect, fluoroscopic time(total
      time)in procedure, it ranged from 3.3 to 64.0 minutes, and DSA images obtained
      ranged from 8 to 280 images. Absorbed dose ranged from 0.3 to 6.0 Gy, with an
      average dose of 3.2 Gy. It thus exceeded 2 or 3 Gy, which was the threshold dose
      of temporary erythematic or depilation in 10 of 14 cases. The maximum dose was
      6.0 Gy for a procedure of percutaneous transhepatic obliteration. The maximum
      exposure dose can be determined objectively by using a film-type dosimeter. It
      was also possible to grasp the overall dose distribution visually.

PMID- 17538226
TI  - [Technical considerations on the usage of a general-purpose flatbed image scanner
      when making a dose-density table].
AB  - The DD-System is a dose-distribution system for analyzing the film method with a
      general-purpose flatbed image scanner. By analyzing the analogue digital
      conversion(ADC)value of each pixel acquired by the DD-system, we examined the
      technical problems of measurement with the scanner when making a dose-density
      table. When film of uniform density was measured, the ADC values distributed
      normally. Deviation of the values at the same pixel point on another time was
      about one-ten thousandth of the average. Deviation of the values from the time
      the scanner was turned on was in the same range. Although it may be negligible,
      the values measured at a peripheral area on the flatbed deviated about 2SD from
      the average measured at the central area. Further, deviation of the value
      obtained with a shade covering the outside of the irradiation field from that
      taken without the shade was about one thousandth. These deviations are not
      negligible. In the case of making a dose-density table with a DD-System and a
      general-purpose flatbed image scanner, the film should be set in the center of
      the flatbed, and the sampling area should be selected from those areas where the
      ADC values are distributed normally. Then proper data can be obtained and more
      accurate tables can be made.

PMID- 17538227
TI  - [Accuracy of volume measurement of lateral atlanto-axial joint by 3D-CT facet
      arthrograms].
AB  - In conventional 3D-CT image processing, the images are influenced by subjective
      threshold settings. The purpose of this study was to evaluate an objective
      threshold setting technique based on the discriminant analysis method. The
      concentration of contrast medium in a joint of a simulated upper cervical spine
      phantom was changed, and its threshold was measured from scanned data by using
      the discriminant analysis method, and mean CT attenuation was measured. On the
      other hand, an accurate image of the corresponding joint in the phantom was made,
      and its minimum threshold was measured. Regression analysis between the adjusted
      minimum threshold and mean CT attenuation of the region of contrast medium was
      performed. The obtained linear regression formula was applied to the threshold
      settings in five cases for atlanto-axial 3D-CT facet arthrogram(3D-CTF), and the
      accuracy of the images was examined. There was a strong correlation between the
      adjusted threshold and mean CT attenuation, and the obtained linear regression
      formula was y=0.625x-141(r2=0.991, p<0.01). This equation could be used
      clinically for correction of the threshold settings. We propose the following
      method for threshold setting of 3D-CTF: the threshold of the region of contrast
      medium is measured using the discriminant analysis method, then the adjusted
      minimum threshold for the threshold settings of 3D-CTF is calculated from mean CT
      attenuation. The method described herein is an objective, general-purpose
      methodology that is applicable to various types of 3D-CT.

PMID- 17538228
TI  - Anxiety-like and exploratory behaviors of isolation-reared mice in the staircase
      test.
AB  - The behavior of isolation-reared mice has not yet been studied in the staircase
      test. The present study examined the effects of anxiolytic or anxiogenic agents
      and isolation rearing on the behavior of ddY (outbred) strain mice in the
      staircase test. Diazepam and phenobarbital increased the number of steps climbed,
      but did not affect rearing behavior in group-reared mice. FG-7142, a
      benzodiazepine inverse agonist, significantly increased the number of rearing
      with no changes in the number of steps climbed in group-reared mice.
      Methamphetamine increased the number of steps climbed and decreased the number of
      rearing in group-reared mice. Although isolation-reared mice showed
      hyperactivity, there was no difference in locomotor activity for the test period
      of 3 min between isolation- and group-reared mice. Under these conditions,
      isolation rearing increased the numbers of steps climbed and rearing compared to
      group-reared controls. Microanalysis of locomotor patterns of group-reared mice
      in the staircase test showed that anxiolytic drugs increased the number of
      climbing to the top step of the staircase and methamphetamine increased the
      number of climbing to the first to third step. These results suggest that
      isolation rearing causes an anxiety-like state with increased exploratory
      behavior in mice.

PMID- 17538229
TI  - Effects of pioglitazone on stearoyl-CoA desaturase in obese Zucker fa/fa rats.
AB  - The effects of a peroxisome proliferator activated receptor gamma (PPARgamma)
      agonist on hepatic stearoyl-CoA desaturase (SCD) in insulin-resistant and obese
      Zucker fa/fa rats were studied. The administration of pioglitazone, a PPARgamma
      agonist, to Zucker obese rats greatly improved their insulin sensitivity. The
      treatment of Zucker obese rats with pioglitazone did not affect the index of
      fatty acid desaturation of either serum or liver. Hepatic SCD activity and the
      mRNA level of SCD1 were not changed by treatment of the rats with pioglitazone.
      The activity of palmitoly-CoA chain elongase, which is involved in the
      biosynthesis of oleic acid in concert with SCD, was not significantly altered
      when Zucker obese rats received pioglitazone. Although neither the activity nor
      mRNA expression of acyl-CoA oxidase was changed by treatment of Zucker obese rats
      with pioglitazone, the mRNA expressions of both sterol regulatory element-binding
      protein-1c and acetyl-CoA carboxylase sensitively responded to the challenge by
      pioglitazone. These results suggest that the insulin sensitivity of insulin
      resistant and obese Zucker fa/fa rats is improved by pioglitazone independently
      of SCD activity.

PMID- 17538230
TI  - Lipopolysaccharide- and glutamate-induced hypothalamic hydroxyl radical elevation
      and fever can be suppressed by N-methyl-D-aspartate-receptor antagonists.
AB  - The purpose of the current study was to explore the effects of N-methyl-D
      aspartate (NMDA)-receptor antagonists (MK-801 and LY235959) administered
      intracerebroventricularly on the changes of both core temperature and
      hypothalamic levels of 2,3-dihydroxybenzoic acid (2,3-DHBA) induced by
      intracerebroventricular injection of glutamate (100 - 400 microg at 10
      microl/rabbit) or intravenous administration of lipopolysaccharide (LPS) (2
      microg/kg) in rabbits. The measurements of 2,3-DHBA were used as an index of the
      intrahypothalamic levels of hydroxyl radicals. The rise in both the core
      temperature and hypothalamic 2,3-DHBA could be induced by intracerebroventricular
      injection of glutamate or intravenous administration of LPS. The glutamate- or
      LPS-induced fever and increased hypothalamic levels of 2,3-DHBA were
      significantly antagonized by pretreatment with injection of MK-801 or LY235959 1
      h before glutamate or LPS injection. The increased levels of prostaglandin E2 in
      the hypothalamus induced by glutamate or LPS could be suppressed by MK-801 or
      LY235959. The data demonstrate that prior antagonism of NMDA receptors in the
      brain, in addition to reducing prostaglandin E2 production in the hypothalamus,
      suppresses both the glutamate- and LPS-induced fever and increased hypothalamic
      hydroxyl radicals.

PMID- 17538231
TI  - Potassium channel opener pinacidil induces relaxation of the isolated human
      radial artery.
AB  - Taking into consideration that the search for drugs capable of modifying blood
      flow through human radial artery (RA) is warranted, the present study was
      designed to examine the vasodilatatory effects of the potassium channel opener,
      pinacidil on the RA and to define the contribution of different K+ -channel
      subtypes in the endothelium-independent pinacidil action on this blood vessel.
      Pinacidil relaxed the RA rings with endothelium and without endothelium with
      comparable potency. N-nitro-L-arginine methyl ester (L-NAME) and methylene blue
      did not affect the pinacidil-induced vasorelaxation in rings with endothelium. In
      the rings without endothelium, the K+ -channel blockers glibenclamide and
      tetraethylammonium (TEA) moderately antagonized the pinacidil-induced relaxation,
      while charybdotoxin and 4-aminopiridine did not. In endothelium-denuded rings,
      precontracted with 100 mM K+, the relaxant responses to pinacidil were highly
      significantly shifted to the right compared to those obtained in RA precontracted
      with phenylephrine, but pinacidil-induced maximal relaxation was not affected.
      Addition of nifedipine did not but addition of nifedipine and nickel (Na+ -Ca2+
      exchanger inhibitor) did cause a statistically significant rightward shift of the
      pinacidil concentration-relaxation curve, although the effect 0.1 mM pinacidil
      was preserved. Thus, pinacidil induces relaxation of the human RA in endothelium
      independent manner, and glibenclamide- and TEA-sensitive vascular smooth muscle
      K+ channels are probably involved. Its ability to completely relax the RA
      precontracted with K+ -rich solution suggests that pinacidil has additional K+
      channel-independent mechanism(s) of action. It seems that stimulation of the
      forward mode of the Na+ -Ca2+ exchanger plays a part in this K+ channel
      independent effect of pinacidil.

PMID- 17538232
TI  - The roles of glial cell line-derived neurotrophic factor, tumor necrosis factor
      alpha, and an inducer of these factors in drug dependence.
AB  - There are few efficacious medications for drug dependence at present. Recent
      evidence has suggested that various cytokines are involved in the effects of
      abused drugs, suggesting that these factors play a role in drug dependence. In
      this article, the roles of glial cell line-derived neurotrophic factor (GDNF) and
      tumor necrosis factor-alpha (TNF-alpha) in drug dependence are discussed. GDNF
      inhibits the cocaine-induced upregulation of tyrosine hydroxylase activity in the
      ventral tegmental area and blocks behavioral responses to cocaine. TNF-alpha
      attenuates rewarding effects and locomotor sensitization induced by
      methamphetamine (METH) and morphine (MOR). Moreover, we mentioned the potential
      of Leu-Ile, which induces the expression of GDNF and TNF-alpha, as a novel
      therapeutic agent for drug dependence. Leu-Ile inhibits not only the development
      but also the maintenance of METH- or MOR-induced place preference and locomotor
      sensitization in mice. The inhibitory effect of Leu-Ile on METH- or MOR-induced
      place preference is not observed in GDNF heterozygous and TNF-alpha knockout
      mice. Leu-Ile inhibits METH- or MOR-induced place preference and sensitization by
      attenuating the METH- or MOR-induced increase in extracellular dopamine levels in
      the nucleus accumbens via the induction of GDNF and TNF-alpha expression. These
      findings suggest that Leu-Ile could be a novel therapeutic agent for drug
      dependence.

PMID- 17538233
TI  - Current topics in the regulatory mechanism underlying the Ca2+ sensitization of
      the contractile apparatus in vascular smooth muscle.
AB  - The Ca2+ signal is the primary determinant of the contraction of the vascular
      smooth muscle. However, the alteration of the Ca2+ sensitivity of the contractile
      apparatus also plays an essential role. The regulation of the myosin light chain
      phosphatase (MLCP) activity is considered to be the most important mechanism
      underlying the regulation of Ca2+ sensitivity. The investigations during the last
      15 years have identified many proteins that participate in the regulation of the
      MLCP activity. Recently, the Ca2+ signal has also been shown to cross-talk with
      the mechanisms regulating the Ca2+ sensitivity. Consequently, Rho kinase, protein
      kinase C, CPI-17, and MYPT1 have all been suggested to play a physiologically
      important role in the regulation of the MLCP activity. We are now close to
      elucidating the major rules regulating the MLCP activity and the Ca2+ sensitivity
      during vascular contractions. This article will give an overview of the current
      understanding of the biochemical basis for the regulation of the MLCP activity,
      while also discussing their functional roles from a physiological point of view.
      I hope this article will help to develop new pharmacological strategies for the
      prevention and treatment of the pathological vasoconstriction often seen in
      vascular diseases.

PMID- 17538234
TI  - Effects of local and whole body irradiation on appearance of osteoclasts during
      wound healing of tooth extraction sockets in rats.
AB  - We examined effects of local and whole body irradiation before tooth extraction
      on appearance and differentiation of osteoclasts in the alveolar bone of rat
      maxillary first molars. Wistar rats weighting 100 g were divided into three
      groups: non-irradiation group, local irradiation group, and whole body
      irradiation group. In the local irradiation group, a field made with lead blocks
      was placed over the maxillary left first molar tooth. In the whole body
      irradiation group, the animals were irradiated in cages. Both groups were
      irradiated at 8 Gy. The number of osteoclasts around the interradicular alveolar
      bone showed chronological changes common to non-irradiated and irradiated
      animals. Several osteoclasts appeared one day after tooth extraction, and the
      maximal peak was observed 3 days after extraction. Local irradiation had no
      difference from non-irradiated controls. In animals receiving whole body
      irradiation, tooth extraction one day after irradiation caused smaller number of
      osteoclasts than that 7 day after irradiation during the experimental period.
      Whole body-irradiated rats had small osteoclasts with only a few nuclei and
      narrow resorption lacunae, indicating deficiency of radioresistant osteoclast
      precursor cells. Injection of intact bone marrow cells to whole body-irradiated
      animals immediately after tooth extraction recovered to some content the number
      of osteoclasts. These findings suggest that bone resorption in the wound healing
      of alveolar socket requires radioresistant, postmitotic osteoclast precursor
      cells from hematopoietic organs, but not from local sources around the alveolar
      socket, at the initial phase of wound healing.

PMID- 17538235
TI  - Evaluation of subchronic chlorpyrifos poisoning on hematological and serum
      biochemical changes in mice and protective effect of vitamin C.
AB  - Chlorpyrifos (CPF) is one of the most widely used organophosphorous insecticides
      in agriculture with its attendant adverse health outcomes. This study aimed at
      evaluating the effect of subchronic oral CPF administration on hematological and
      serum biochemical indices, and the possible ameliorating effect of vitamin C on
      the indices in mice. Thirty mice divided into 3 groups of 10 mice each were used
      for this study. Mice in group I (control) were dosed with vegetable oil, while
      those in group II were given CPF (21.3 mg/kg~ 1/5(th) LD(50)) only. Mice in group
      III were pretreated with vitamin C (100 mg/kg) prior to dosing with CPF 30 min
      later (Vitamin C + CPF-treated group). This regime was given to each group of
      mice three times a week for a period of ten weeks. During the study period, mice
      were examined for signs of toxicity, and weight of each mouse was measured every
      week. At the end of the study period, blood samples were collected from the mice
      and analyzed for packed cell volume (PCV), total red blood cell (RBC), white
      blood cell (WBC) and total protein (TP). Serum obtained from the blood was
      analyzed for Na( +, K+ and Cl-), urea, creatinine, alanine aminotransferase
      (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP). The
      results showed that mice in the vitamin C + CPF-treated group exhibited milder
      signs of toxicity and significant increase in weight gain (p<0.01) compared to
      the CPF-treated group. No significant increase in weight in the CPF-treated group
      was observed compared to the control. There was a significant increase in PCV,
      RBC, Hb, TP and creatinine, but a significant decrease was obtained in WBC, ALT
      and AST in the CPF-treated group compared to the control. All the parameters with
      the exception of WBC, ALT and AST (which increased significantly), were
      significantly decreased in the vitamin C + CPF-treated group compared to CPF
      treated group. ALP was significantly elevated in the CPF-treated group compared
      to both the control and vitamin C + CPF-treated group. No significant changes in
      urea and the measured electrolytes in all three groups, except a significant
      decrease in the concentration of Na(+) was observed in the CPF-treated group
      compared to the control. The study demonstrated that pretreatment of CPF
      administered mice with vitamin C significantly altered some important
      hematological and serum biochemical parameters, revealing the protective action
      of the vitamin against some organ damage induced by CPF.

PMID- 17538236
TI  - Comparison of peroxidase response to mental arithmetic stress in saliva of
      smokers and non-smokers.
AB  - Saliva is the first body fluid to encounter exogenous materials or gases such as
      cigarette smoke (CS). The aim of this study was to examine whether smoking
      affects oral peroxidase (OPO) reactivity to mental stress. The subjects were 39
      non-smokers and 10 smokers. In the experiment, the Kraepelin psychodiagnostic
      test as a psychological stressor and saliva was sampled 30 min before, just
      before, immediately after, and 30 min after the beginning of the test. OPO
      reactivity to the test between smokers and non-smokers was measured in addition
      to uric acid concentration, flow rate, IgA, thiocyanate (SCN-) concentration,
      amylase activity as a salivary stress marker, and ultra-weak chemiluminescence
      (UCL) level, which is indicative of salivary antioxidative and antibacterial
      abilities. Moreover, we studied the effect of smoking on the response of salivary
      peroxidase (SPO) and myeloperoxidase (MPO) activity to mental stress,
      respectively. The results showed that the IgA concentration, amylase activity,
      SCN(- concentration, and UCL level are higher in the non-smoking group than
      smoking group and the IgA concentration and UCL level increased in the non
      smokers significantly just after the Kraepelin test. The levels of SCN-) were
      higher in smokers than in non-smokers and OPO activity was greater in the non
      smoking group in all sessions. Furthermore, only the non-smokers had
      significantly increased MPO activity just after the test. MPO may play a crucial
      role in the response to acute psychological stress besides inflammation, and CS
      suppresses this response significantly.

PMID- 17538237
TI  - Characterization of resistance to bromobenzene-induced hepatotoxicity by
      microarray.
AB  - In our previous study, we demonstrated that the initial hepatic injury caused by
      bromobenzene (BB) was no longer detected in rats despite subsequent dosing,
      indicating that the liver acquired resistance to BB-induced hepatotoxicity. In
      this experiment, microarray analysis was conducted to characterize this
      resistance. The liver samples for the analysis utilized were obtained from
      previous experiments where F344 rats were treated intraperitoneally with BB (150
      mg/kg). At 24 hr post-dose, hepatic injury was confirmed by monitoring the AST
      values and then the rats were maintained at the same dosing regimen for an
      additional 8 days. The gene expression profiles of the BB-treated rat livers were
      compared with a vehicle-treated group by Affymetrix RG_U34A arrays. As results, a
      decreased expression level of CYP3A9 and an increased expression level of GST Yc2
      and glutathione peroxidase (GPX) were detected. These changes indicated
      suppression of the phase I reaction and induction of the phase II reaction
      (glutathione conjugation). Increased expression levels of epoxide hydrolase (EH)
      and NAD(P)H:quinone oxidoreductase (NQO1) also suggested the involvement of EH-
      and NQO1-mediated hydrolysis other than glutathione conjugation with resistance
      in the phase II reaction. Moreover, an increased expression level of abcc3
      (multidrug resistance protein 3; Mrp3) was significantly noted. Based on the
      present findings, it was suggested that Mrp3 in the phase III reaction (drug
      elimination) contributed to the resistance to BB hepatotoxicity in addition to
      the suppression of the phase I reaction (metabolic activation) and the induction
      of the phase II reaction (detoxification). Among them, the factors which
      contributed most were considered to be the increased GST Yc2 and Mrp3, based on
      the degree of the gene expression changes.

PMID- 17538238
TI  - Native state of metals in non-digested tissues by partial least squares
      regression analysis of visible and near-infrared spectra.
AB  - A procedure has been used for the classification and quantification of metals on
      the basis of a chemometric analysis of visible and near-infrared (Vis-NIR)
      spectra of metals such as Cu, Mn and Fe in the brain, liver, kidney and testis of
      mice without digestion. Transmittance spectra in the 600- to 1000-nm region
      subjected to partial least-squares (PLS) regression analysis and leave-out cross
      validation facilitated development of chemometrics models for predicting metal
      concentration. From the models, Cu, Mn and Fe yielded the coefficients of
      determination in cross-validation (R(2)(VAL)) as 0.8013, 0.9021 and 0.8295 with
      standard errors of cross-validation (SECV) of 3.399, 0.8237 and 76.512 microg per
      g tissue, respectively. The respective detection limits of Cu, Mn and Fe were
      12.19, 2.616 and 266.32 microg per g tissue. Furthermore, the regression
      coefficients of the models showed specific patterns for the respective metals.
      These results suggest that Vis-NIR spectroscopy may have a great potential for
      analysis of native state of metals in tissues.

PMID- 17538239
TI  - Kojic acid -absence of tumor-initiating activity in rat liver, and of
      carcinogenic and photo-genotoxic potential in mouse skin.
AB  - Kojic acid (KA) has been widely used as a quasi-drug ingredient. Possible
      promotion activity of KA was suggested on livers of mouse and rat by findings
      obtained in genotoxicity and carcinogenicity studies performed thus far.
      Therefore, in order to examine safety as a quasi-drug ingredient, we investigated
      the presence of initiation activity in rat liver and the photo-genotoxicity and
      carcinogenicity in mouse skin. In medium-term carcinogenesis test in rats, 2.0%
      KA was orally given to F344/DuCrj rats for 4 weeks of the initiation period,
      followed by the combination of partial hepatectomy and treatment with a
      hepatocarcinogenesis promoter, phenobarbital (PB). As a result, glutathione S
      transferase placental form (GST-P) positive foci of 0.2 mm or more in diameter in
      the KA group, which is usually used in determination of pre-cancerous lesions,
      did not increase significantly in both numbers and areas compared with those of
      the non-initiated controls. In the concurrent analysis, however, numbers of GST-P
      positive foci of two cells or more and 0.1 mm or more in diameter increased
      slightly, and possible weak initiation activity of KA was equivocal. However,
      considering the known fact that KA exerts promotion activity in the liver of F344
      rats by long-term dietary administration, it was suggested that the observed
      slight increase of the numbers of GST-P-positive foci in rat liver was the effect
      of promotion activity of KA rather than the initiation activity. In DNA adducts
      formation assay in a rat liver, no clear adducts derived from KA were detected in
      male F344/DuCrj rats administered 0.5% or 2% KA orally, and KA was considered not
      to form DNA adducts in rat liver. In the in vitro photo-reverse mutation assay
      with bacteria, KA exerted weak photo-mutagenicity. Furthermore, in chromosome
      aberration study in Chinese hamster lung cells (CHL/IU cells) with UV
      irradiation, KA induced chromosome aberration at high-dose (1.4 mg/mL) treatment
      with UV irradiation, but was negative without UV irradiation. However, in the in
      vivo photo-micronucleus study in mouse, in which 1.0 or 3.0% KA containing cream
      was applied twice to the back of the animals with a 24-hr interval, KA did not
      induce micronuclei in mouse epidermal cells. Based on these results, it is
      considered that the risk of KA to exert photo-carcinogenicity is quite low in the
      skin. In skin carcinogenesis bioassay for initiation-promotion potential, 3.0% KA
      cream formulation was applied to the back of the mouse for 1 week (once a day,
      total 7 times) and for 19 weeks (5 times a week, total 95 times) during the
      initiation and the promotion stages, respectively. No skin nodules were observed
      in any animal skins formed due to KA treatment given in either stage. Therefore,
      KA is considered not to possess initiation nor promotion activity of skin
      carcinogenesis. Furthermore, from the above findings, it is suggested that KA is
      virtually safe as a quasi-drug ingredient.

PMID- 17538240
TI  - Hepatic and intestinal changes in rats treated with T-0126, a microsomal
      triglyceride transfer protein (mtp) inhibitor.
AB  - In the present study, we investigated the potential toxic effects of 2-week oral
      treatment with T-0126, a novel microsomal triglyceride transfer protein (MTP)
      inhibitor, on the liver and intestine in male and female rats. Administration of
      T-0126 decreased serum lipids and resulted in fat accumulation in the liver and
      the small intestine. In addition, slight changes in the liver, including an
      increase in serum aminotransferase (AST and ALT) activity, presence of focal
      inflammatory lesions, and prolongation of PT and APTT were observed after
      treatment with T-0126. These changes may be related to a mechanism based on
      malabsorption of fat, fat-soluble antioxidants, and vitamin K, although we cannot
      exclude other potential mechanisms such as direct cytotoxicity of T-0126.

PMID- 17538241
TI  - Problems of positive list system revealed by survey of pesticide residue in food.
AB  - The positive list system became effective from May 29, 2006 to improve the
      regulation of residual agricultural chemicals (pesticides, feed additives and
      veterinary drugs) in foods. In accordance with the system, we investigated
      pesticide residues in 50 agricultural products purchased in Morioka city from
      March to November 2006. Analyses were performed according to the "Multiresidue
      Method for Agricultural Chemicals by GC/MS", the Notice of the Ministry of
      Health, Labour and Welfare. Five pesticides and two non-agricultural chemicals
      were detected from 16 samples. Ortho-phenylphenol (OPP) was detected from 8
      samples: immature pea, snap bean, kiwi, plain-boiled bamboo shoot, mango, white
      asparagus, lemon and domestic shiitake mushroom. Maximum residue limits (MRLs)
      have not been established for these products, and they exceeded the uniform level
      of 0.01 ppm. DDT was detected from Philippines banana (0.30 ppm) and Korean
      paprika (0.45 ppm). The residual level in Philippines banana was lower than the
      MRL, but Korean paprika exceeded its MRL. Chlorpyrifos, Thiabendazole and
      Imazaril were detected from citrus imported from the U.S.A., but their residue
      levels were lower than the respective MRLs. Aniline and 2-pyrrolidone were
      detected from several imported products. These two may not be regulated by the
      positive list system because they are not agricultural chemicals, although their
      derivatives are used as pesticides or veterinary drugs. Three problems have been
      revealed from this survey: 1) application of the uniform level to minor
      agricultural products, 2) residues of non-agricultural chemicals whose toxicity
      is uncertain, 3) metabolites of agricultural chemicals, which are also regulated
      by the positive list system, have not been clearly defined.

PMID- 17538242
TI  - Effect of tiron and its combination with nutritional supplements against vanadium
      intoxication in female albino rats.
AB  - In the present study an attempt has been made to evaluate the effect of Tiron
      along with Zinc, Selenium and Vitamin E against vanadium intoxication in female
      albino rats. Toxicant caused significant increase in the activities of serum
      transaminases, serum alkaline phosphatase and lactate dehydrogenase. Significant
      decrease was observed in blood sugar, serum albumin and triglyceride levels
      whereas serum proteins, cholesterol and urea levels increased significantly
      during toxicity (p </= 0.001). Hepatic lipid peroxidation increased
      significantly, whereas significant depletion was observed in reduced glutathione
      after vanadium administration. The activity of glucose-6-phosphatase in the liver
      was also inhibited significantly after vanadium administration. A significant
      rise was observed in glycogen content of liver and kidney after toxicant
      exposure. Activities of alkaline phosphatase, adenosine triphosphatase and
      succinic dehydrogenase were inhibited significantly on the contrary activity of
      acid phosphatase elevated in kidney. Histopathological examination of the liver
      and kidney using light and ultramicroscopic study also substantiated the above
      findings. It was found that therapy with Tiron was effective but significant
      recovery in all the parameters was found with Tiron + Se followed by Tiron+ VitE
      and Tiron +Zn.

PMID- 17538243
TI  - Gene expression profile in human cells exposed to zinc.
AB  - Although Zn is an essential trace metal for humans, a comprehensive view of its
      effects on cellular functions has not been obtained. We used a DNA microarray to
      assess transcriptional alterations in human HeLa cells after exposure to a
      moderate concentration of Zn (100 muM ZnSO(4)). Out of 9,182 human genes,
      expression was increased in 7 genes and decreased in 4 genes twofold or greater.
      Four of the 7 upregulated genes were those coding for metallothionein isoforms or
      related proteins. An unexpectedly small extent of changes in gene expression
      might reflect rapid sequestration of Zn ions by metallothioneins, and the absence
      of most of the other protective responses indicated the non-toxic nature of Zn at
      this concentration. Comparison with our previous DNA microarray results for 5 muM
      CdSO(4)-exposed HeLa cells revealed several genes that are regulated by both
      metals in parallel, and a gene reciprocally regulated by them.

PMID- 17538244
TI  - An unusual toxic cause of hemolytic-uremic syndrome.
AB  - Hemolytic uremic syndrome (HUS) has been associated with a variety of infective
      as well as non-infective causes. HUS as a toxic manifestation of exposure to
      herbicides/pesticides has not been reported so far in literature. We report a
      subject who presented with clinical features of features of HUS after intentional
      suicidal ingestion of the herbicidal agent monochloroacetic acid (MCA). A 55-year
      old farmer was admitted with a history of consumption of monochloroacetic acid
      with vomiting, hematochezia and oligo-anuria. Our investigations revealed severe
      renal failure, metabolic acidosis, anemia, and thrombocytopenia with evidence of
      intravascular hemolysis. He was treated for HUS with plasma transfusions and
      haemodialysis in view of renal failure. During the course of hospital admission
      he developed acute antero-septal myocardial infarction and subsequently succumbed
      to the disease. MCA is used as an herbicidal agent and also a bleaching agent for
      silkworm cocoons. The toxicity of MCA has included metabolic acidosis,
      rhabdomyolysis and renal failure; however HUS has not been described in the
      literature. Extra -renal manifestations of HUS such as cardiomyopathy have also
      been infrequently described. This case is presented to highlight an as yet
      unknown toxicity of MCA.

PMID- 17538245
TI  - DNA microarray analysis of transcriptional responses of yeast cells to expression
      of core protein of hepatitis C virus.
AB  - We monitored transcriptional changes in yeast cells in response to induced
      expression of the core protein of hepatitis C virus (HCV) using a DNA microarray.
      Expression of 16 genes involved in the unfolded-protein response was enhanced by
      inducing expression of the core protein in yeast cells.

PMID- 17538246
TI  - Liposomal amphotericin B can safely be administered in paediatric outpatients
      with cancer for the primary or secondary prevention of invasive aspergillosis.

PMID- 17538247
TI  - Sustained leukocyte count during rising cortisol level.
AB  - AIMS: To follow the trend of leukocyte counts relative to the serum cortisol
      levels in hospitalized patients. METHODS: We retrospectively reviewed the charts
      of 59 hospitalized patients who had sequential blood profiles during a 2-week
      period. RESULTS: The study cohort was divided into two subgroups according to the
      categorical cortisol levels: those within the normal range (< 25 microg/dl; n =
      31 patients) and those above the normal range (> or = 25 microg/dl; n = 28
      patients). The baseline white blood cell counts (WBCCs) were similar in both
      groups. After 1 week, however, the WBCCs dropped significantly in the presence of
      normal cortisol levels and increased in the presence of elevated cortisol levels
      (p = 0.002). This pattern was not followed by the platelet counts. A significant
      correlation was observed between the cortisol levels and the 1 week concomitant
      WBCC (r = 0.33). CONCLUSION: Cortisol may be the mechanism with a positive effect
      on the maintenance of elevated leukocyte counts.

PMID- 17538248
TI  - Imatinib and nilotinib induce apoptosis of chronic myeloid leukemia cells through
      a Bim-dependant pathway modulated by cytokines.
AB  - It is an important challenge to better understand the mechanisms of tyrosine
      kinase inhibitors-induced apoptosis in CML cells. Thus, we have investigated how
      this apoptosis can be modulated by extracellular factors. Apoptosis induced by
      imatinib and nilotinib was determined in BCR-ABL expressing cell lines and
      primary CML CD34+ cells. Both molecules induced apoptosis of BCR-ABL expressing
      cells. This apoptosis was inhibited by protein synthesis inhibition in both K562
      and CML CD34+ cells. In K562, 80% inhibition of the BCR-ABL auto-phosphorylation
      by either imatinib or nilotinib induced a two fold increase in Bim-EL expression
      and induction of apoptosis in 48 h. Bim accumulation preceded apoptosis induction
      which was completely abolished by depletion in Bim using shRNA. However, the anti
      proliferative effect of imatinib was preserved in Bim-depleted cells. When K562
      cells were cultured in a cytokine containing medium, the pro-apoptotic effect of
      nilotinib was decreased by 68% and this was related to a decrease in Bim-EL
      dephosphorylation and accumulation. Similarly, the presence of a combination of
      cytokines inhibited 88% of NIL- and 39% of IMA-induced apoptosis in primary CML
      CD34+ cells. In conclusion, both nilotinib and imatinib induce apoptosis through
      Bim accumulation independently of cell cycle arrest. However, the pro-apoptotic
      effect of both molecules can be attenuated by the presence of cytokines and
      growth factors, particularly concerning nilotinib. Thus BCR-ABL inhibition
      restores the cytokine dependence but is not sufficient to induce apoptosis when
      other signaling pathways are activated.

PMID- 17538250
TI  - Clinical clarifications requested.

PMID- 17538255
TI  - Managing fungating wounds.

PMID- 17538256
TI  - Preventing and treating skin tears.

PMID- 17538257
TI  - The state of wound care in the United Kingdom.

PMID- 17538258
TI  - So what if you are blue? Oral colloidal silver and argyria are out: safe
      dressings are in.

PMID- 17538259
TI  - Bactericidal and cytotoxic effects of chloramine-T on wound pathogens and human
      fibroblasts in vitro.
AB  - OBJECTIVES: To evaluate cytotoxicity and bactericidal effects of chloramine-T.
      METHODS: In vitro study of various concentrations and exposure times to
      preparations containing human fibroblasts or 1.5 x 10 colony forming units per
      milliliter (CFU/mL) of 3 gram-positive bacteria-Staphylococcus aureus,
      methicillin-resistant S aureus, and vancomycin-resistant Enterococcus faecalis
      and 2 gram-negative bacteria-Escherichia coli and Pseudomonas aeruginosa-with and
      without fetal bovine serum present. MAIN OUTCOME MEASURES: Percentage reduction
      of bacterial growth and percentage of viable fibroblasts 48 hours after exposure.
      RESULTS: All gram-positive growth was reduced by 95% to 100%, regardless of dose,
      with or without serum. E coli (gram-negative; with/without serum) was reduced 94%
      to 100% at antiseptic concentrations of 300 and 400 ppm. At 200 ppm, E coli
      growth was fully inhibited without serum present and by 50% with serum. P
      aeruginosa (gram-negative) was not significantly affected under any conditions.
      At 100 and 200 ppm, cell viability remained greater than 90% under all
      experimental conditions. A 300-ppm, 3-minute exposure to chloramine-T resulted in
      cell viability of up to 70%, with longer exposures producing lower viabilities.
      Serum did not affect cell viability in any condition. CONCLUSIONS: In vitro,
      chloramine-T at 200 ppm for 5 to 20 minutes was effective against 3 virulent gram
      positive bacteria without fibroblast damage. At 300 ppm and 3 and 5 minutes, 30%
      of fibroblasts were damaged and 95% to 100 % of E coli were inhibited,
      respectively.

PMID- 17538260
TI  - Common nail disorders and fungal infections.
AB  - PURPOSE: To provide the practitioner with current information on the most common
      nail disorders. TARGET AUDIENCE: This continuing education activity is intended
      for physicians and nurses with an interest in wound care and related disorders.
      OBJECTIVES: After reading this article and taking this test, the reader should be
      able to: 1. Describe the structures that compose the nail apparatus. 2. Identify
      the most common nail disorders, including etiology and treatment.

PMID- 17538262
TI  - Cultural competence among staff nurses who participated in a family-centered
      geriatric care program.
AB  - The purpose of this training program was to prepare nursing staff in family
      centered geriatric care that emphasizes providing culturally competent care to
      hospitalized elders at two major tertiary hospitals in New York. This research
      report corresponds to the first phase of a 3-year project. In this research
      project, a descriptive exploratory design was used to identify the levels of
      cultural awareness and cultural competence of nursing staff who participated in a
      family-centered geriatric care training program.

PMID- 17538264
TI  - Discourse analysis of nurse-patient communication in a hospital setting:
      implications for staff development.
AB  - This ethnographic study examined the symmetry (active listening)/asymmetry
      (dominance) of nurse-patient communication. A convenience sample of 20 gendered
      nurse-patient pairs from two community hospitals participated. Eleven discourse
      modes emerged from taped conversations between nurses and patients. In many nurse
      patient interactions, nurses demonstrated symmetry; however, symmetry and
      asymmetry changed throughout the conversation. Nurses often missed cues that
      patients needed someone to listen to their concerns. Staff development
      implications include teaching strategies that increase symmetrical nurse-patient
      communication.

PMID- 17538266
TI  - The nursing professional portfolio: a pathway to career development.
AB  - Nursing professional portfolios have moved beyond the traditional listing of past
      experiences and accomplishments. They now provide a format for self-reflection on
      practice and for goal planning, capturing both the art and the science of
      nursing. This article describes the experiences of designing and implementing the
      use of a comprehensive professional portfolio and the benefits realized by
      individual staff nurses and their managers.

PMID- 17538267
TI  - Continuous automated pressure ulcer monitoring.
AB  - In the spring of 2002, the nurses working in a 300-bed Midwest care center
      embarked on a mission to decrease patient suffering from skin breakdown and
      pressure ulcers. A continuous automated pressure ulcer monitoring system was
      developed to improve decision making and identify educational needs. As a result,
      the nurses have changed the skin culture of the facility and positively affected
      the rate of hospital-acquired pressure ulcers and non-pressure-related breakdown.

PMID- 17538268
TI  - Simulator programs for new nurses' orientation: a retention strategy.
AB  - The phenomenon of role transition for new nurses has been a topic of research and
      concern for practicing nurses, educators, and administrators for many years. This
      transition has an impact on the job retention of new nurses. Stress, lack of
      confidence, and unmet expectations have been found to influence patient safety
      and outcomes. Simulator programs have enhanced the experiences of students and
      nurses in the clinical setting. Within this safe environment of simulation,
      nurses find the opportunity to develop critical thinking, decision making, and
      clinical confidence. A simulator program was developed in Vassar Brothers Medical
      Center to assist in the transition of new graduate registered nurses to acute
      care practice. This article describes the process of developing a program and
      suggestions for instructors who are interested in developing a simulation
      program.

PMID- 17538269
TI  - Unraveling the mystery of a code: engaging staff through hands-on practice.
AB  - A three-part, hands-on educational series named "Crash Course" was developed in
      response to staff members verbalizing fear of code management, equipment use, and
      their role in assisting in a code. These three courses were 1 hr in length,
      provided hands-on practice, and offered contact hour credit. Each attendee was
      expected to participate through demonstration and open discussion. The purpose of
      this article is to explain how staff development educators can create this
      learning experience for nursing staff and engage them in hands-on code management
      practices.

PMID- 17538270
TI  - Collaboration: a community effort to create a standardized orientation program
      for nursing students.
AB  - Nursing students require orientation to all healthcare facilities where they are
      assigned for clinical training. The coordination of orientation for the students
      is time consuming and labor intensive. Seven healthcare facilities and three
      universities collaborated to develop an online computer orientation program for
      all nursing students in the community. The program standardized the education
      content, decreased faculty instruction time, and facilitated the transition of
      nursing students into the clinical area.

PMID- 17538271
TI  - Instant teaching tools.

PMID- 17538272
TI  - Needs...wants...demands: part 1.

PMID- 17538273
TI  - The role of staff development/staff development specialist in achieving and
      maintaining Magnet designation.

PMID- 17538274
TI  - Pictorial essay: diverse imaging features of spinal schwannomas.
AB  - In this pictorial review, we present diverse imaging features of spinal
      schwannomas with an idea to familiarize spine imagers with the varied spectrum of
      presentation of these tumors. Different types of spinal schwannomas presented
      include multiple schwannoma (n = 3), schwannoma with cystic degeneration (n = 3),
      schwannoma with hemorrhage (n = 2), melanotic schwannoma (n = 1), intraosseous
      schwannoma (n = 2), schwannoma growing into the foramen transversarium (n = 1),
      intramedullary schwannoma (n = 1), large or giant schwannoma (n = 1), malignant
      schwannoma (n = 2), and infarcted schwannoma (n = 1). We present imaging findings
      in these cases and review their differential diagnosis. Awareness of the uncommon
      presentations of these seemingly common tumors is important in offering a correct
      diagnosis.

PMID- 17538275
TI  - Relative cerebral blood volume is a measure of angiogenesis in brain tuberculoma.
AB  - OBJECTIVE: The aim of this study was to correlate the perfusion indices with
      magnetic resonance imaging-derived cellular and necrotic fraction of the
      tuberculoma and angiogenesis metrics on histopathology. METHODS: We performed
      dynamic contrast-enhanced magnetic resonance imaging in 13 excised brain
      tuberculoma patients. Microvascular density and vascular endothelial growth
      factor (VEGF)-expressing cells were quantified from the excised tuberculoma. The
      cellular and necrotic fractions of the tuberculomas were quantified on a
      postcontrast T1-weighted imaging. RESULTS: Relative cerebral blood volume of
      cellular portion significantly correlated with cellular fraction volume (r =
      0.882, P < 0.001), microvascular density (r = 0.900, P < 0.001), and VEGF (r =
      0.886, P < 0.001) of the 13 excised tuberculomas. Microvascular density also
      correlated significantly with VEGF (r = 0.919, P < 0.001). CONCLUSIONS: Relative
      cerebral blood volume is a measure of angiogenesis in the cellular fraction of
      the brain tuberculoma. This information may be of value in predicting the
      therapeutic response in future.

PMID- 17538276
TI  - Efficacy of multidetector row computed tomography of the spine in patients with
      multiple myeloma: comparison with magnetic resonance imaging and
      fluorodeoxyglucose-positron emission tomography.
AB  - PURPOSE: The aim of our study was to compare the efficacy of multidetector row
      computed tomography (MDCT) with magnetic resonance imaging (MRI) and
      fluorodeoxyglucose-positron emission tomography (FDG-PET) for detection of spinal
      bone marrow involvement in patients with multiple myeloma. MATERIALS AND METHODS:
      Ten patients with multiple myeloma stage III underwent MDCT and MRI of the spine
      and FDG-PET. The number and location of lesions detected by 3 modalities were
      recorded, and a lesion-by-lesion analysis was completed, using McNemar test. For
      MDCT, image analysis was performed according to the type of lesion (established
      by Laroche et al), and the efficacy of lesion detection was compared with that of
      the MRI and FDG-PET. P values less than 0.05 were considered statistically
      significant. RESULTS: The MDCT, MRI, and FDG-PET detected the following numbers
      of lesions: 102 of 140 vertebrae, 95 of 140 vertebrae, and 84 of 140 vertebrae,
      respectively. The difference between the abilities of MDCT and MRI to detect
      lesions was not statistically significant (P = 0.289). However, the difference in
      effectiveness between MDCT and FDG-PET was statistically significant (P < 0.001).
      For small osteolytic lesions, less than 5 mm, the difference in effectiveness
      between MDCT and MRI was also statistically significant (P = 0.031). CONCLUSIONS:
      The MDCT is very sensitive in detecting small osteolytic lesions in the spine, as
      compared with MRI and FDG-PET.

PMID- 17538277
TI  - Fluid-attenuated inversion recovery ring sign as a marker of dysembryoplastic
      neuroepithelial tumors.
AB  - PURPOSE: The aim of our study is to describe the hyperintense ring sign on fluid
      attenuated inversion recovery (FLAIR) images in patients with dysembryoplastic
      neuroepithelial tumors (DNET), to discuss the radiopathologic correlation for
      this appearance, and to determine its role in preoperative diagnosis of DNETs.
      MATERIALS AND METHODS: We retrospectively analyzed imaging features in 11
      patients with pathological diagnosis of DNET. All patients had undergone surgery
      for refractory seizures. All had FLAIR imaging sequences performed on a 1.5-T
      magnetic resonance scanner. Clinical and pathological details in all cases were
      examined. Twenty-one age matched patients with pathologically confirmed low-grade
      glioma (n = 11), oligodendroglioma (n = 2), and ganglioglioma (n = 8) in similar
      locations acted as control cases. Ten patients had follow-up imaging. RESULTS:
      There were 11 patients with DNET (5 girls and 6 boys). The age of presentation
      varied from 4 to 18 years (average, 9 years 1 month). Tumors were located in the
      temporal (n = 5), frontal (n = 4), parietal (n = 1), and occipital (n = 1) lobes.
      In 9 patients (82% sensitivity), the FLAIR images showed a well-defined
      hyperintense ring around these tumors, either as a complete or incomplete ring.
      Among the 21 control cases, the hyperintense ring sign was seen in 2 cases (90%
      specificity): one with low-grade glioma and one with ganglioglioma. Pathological
      evaluation of the DNETs suggested the hyperintense ring might correspond to the
      presence of peripheral loose neuroglial elements. Postoperative imaging showed
      partial residual ring in 3 patients, all of whom had persistent seizures. One
      patient had recurrent DNET at second surgery. CONCLUSION: Magnetic resonance
      imaging findings of DNET are well described. We describe an additional imaging
      sign, the hyperintense ring sign on FLAIR images, which is distinct and is fairly
      sensitive and specific for DNET. We believe this sign is a helpful adjuvant to
      preoperatively diagnose these tumors. The presence of this ring on postoperative
      imaging may indicate residual or recurrent tumor.

PMID- 17538278
TI  - Dynamic magnetic resonance imaging evaluation of craniovertebral junction
      abnormalities.
AB  - OBJECTIVES: To evaluate the role of dynamic magnetic resonance imaging (MRI) in
      craniovertebral junction (CVJ) abnormalities. MATERIALS AND METHODS: Twenty-five
      patients with suspected CVJ abnormalities underwent dynamic MRI of the CVJ, and
      in 20 of these patients, noncontrast computed tomography scan of the CVJ was
      done. The images were evaluated for atlantoaxial instability (AAI), spinal canal
      narrowing, cord compression, presence of altered cord signal intensity, and bony
      abnormalities in neutral, flexion, and extension. RESULTS: Dynamic MRI detected
      15 cases of AAI (10 fixed and 5 mobile AAI), 21 patients had varying degrees of
      spinal canal narrowing. Five patients showed increased narrowing on
      flexion/extension. Two patients demonstrated direct cord compression in flexion,
      whereas in neutral position, only dural compression was seen. One patient had
      cord compression on extension that was not seen in neutral or flexed position.
      CONCLUSION: Dynamic MRI was able to detect cases of cord compression that were
      not seen in neutral position and was diagnostic in all cases of mobile AAI where
      mobility at this joint affects the treatment options. Dynamic MRI is extremely
      useful for evaluating craniovertebral junction abnormalities and, in particular,
      cord compression.

PMID- 17538279
TI  - Venous reflux on carotid computed tomography angiography: relationship with left
      arm injection.
AB  - OBJECTIVE: We evaluated the relationship between image degradation due to the
      reflux of contrast agent into the major neck veins and use of a left-arm
      injection site during computed tomographic (CT) angiography of the carotid
      arteries. METHODS: A total of 364 patients underwent 4-section carotid CT
      angiography performed with an injection into the right (n = 183) or left (n =
      181) arm. We calculated the volume of refluxed contrast medium and measured the
      retrosternal distance measured as the shortest distance between the sternum and
      the arch or its branches. Nine patients underwent follow-up CT angiography weeks
      later by using the side of injection not used before for comparison. RESULTS: The
      amount of refluxed contrast medium was greater with left-arm injection than with
      right-arm injection (P < 0.001). With left-arm injection, the volume was
      significantly correlated with the retrosternal distance (r = -0.514, P < 0.001),
      even after we adjusted for age and sex in the linear regression model (P <
      0.001). Five of the 9 patients who received injections in both arms had no reflux
      of contrast medium, whereas 4 patients had obvious reflux after left-arm but not
      right-arm injection. CONCLUSION: Normal compression of the left brachiocephalic
      vein due to a developmental decreased retrosternal space may degrade carotid CT
      angiograms because of reflux of contrast material into the cervical veins. This
      degradation can be avoided if right-arm injection is used.

PMID- 17538280
TI  - Partial duplication of the hypophysis in adult patients: report of 2 cases.
AB  - Complete duplication of the pituitary gland is an extremely rare condition which
      is associated with a wide range of anomalies. An incomplete duplication affecting
      only the anterior pituitary gland or the pituitary stalk has not been described
      so far. We report 2 such cases of partial duplication of the hypophysis and
      briefly review the literature.

PMID- 17538281
TI  - Rhabdomyolysis: magnetic resonance imaging and computed tomography findings.
AB  - OBJECTIVE: Our purpose was to describe the magnetic resonance (MR) imaging and
      computed tomography (CT) findings in patients with rhabdomyolysis. METHODS: The
      medical records and imaging studies of 10 patients (5 males, 5 females; age
      range, 14-60 years; mean age, 28.3 years) with rhabdomyolysis were
      retrospectively reviewed. Magnetic resonance imaging was available in 9 patients
      and CT in 2 patients. RESULTS: Two distinct imaging types of rhabdomyolysis were
      observed. For type 1 rhabdomyolysis (n = 2), the affected muscles revealed
      homogeneously isointense to hyperintense on T1-weighted, homogeneously
      hyperintense on T2-weighted and short-tau inversion recovery (STIR) images, and
      homogeneously enhanced on contrast-enhanced MR images. For type 2 rhabdomyolysis
      (n = 8), the affected muscles revealed homogeneously or heterogeneously
      isointense to hyperintense on T1-weighted images, heterogeneously hyperintense on
      T2-weighted and STIR images, heterogeneously hypodense on CT images, and rim
      enhanced on contrast-enhanced MR and CT images with the presence of a specific
      presentation, named as the "stipple sign." CONCLUSIONS: Rhabdomyolysis is a
      clinical and biochemical syndrome comprising 2 distinct imaging types.
      Homogeneous signal changes and enhancement in the affected muscles advocate type
      1 rhabdomyolysis. The stipple sign is helpful in demonstrating the areas of
      myonecrosis in type 2 rhabdomyolysis and, together with clinical and laboratory
      presentations, in reaching the correct diagnosis.

PMID- 17538282
TI  - Infection scintigraphy: added value of single-photon emission computed
      tomography/computed tomography fusion compared with traditional analysis.
AB  - PURPOSE: Positron emission tomography (PET)/computed tomography (CT) imaging is a
      powerful dual-modality integrating physiology and anatomy. Analogously, fusing
      separate single-photon emission computed tomography (SPECT) and CT images can
      overcome interpretive challenges in characterizing and localizing abnormalities.
      This study explores the value of SPECT/CT image fusion compared with traditional
      "side-by-side" SPECT-CT image review for infectious /inflammatory processes.
      METHODS AND MATERIALS: We identified 17 abnormal infection/inflammation SPECT
      scans in 16 patients (11 indium 111 WBC and 6 gallium citrate Ga 67) with a
      contemporary CT scan. The SPECT and CT images were uploaded onto "side-by-side"
      workstations, one with fusion software. Two nuclear radiologists reviewed "side
      by-side" SPECT and CT images and fused SPECT/CT images. They scored 2 parameters
      (anatomical localization and diagnostic confidence) using a 4-point scale (1 "not
      helpful" to 4 "very helpful"). Score differences more than 1 indicated "added
      value" and less than 0, "no added value". RESULTS: Compared with "side-by-side"
      SPECT-CT, fused SPECT/CT images yielded "added value" for anatomical localization
      in 65%, diagnostic confidence in 71%, and altered interpretations in 47% of
      cases. Greater confidence was achieved in 75% of cases with altered
      interpretations and 55% of unaltered cases. CONCLUSIONS: The SPECT/CT image
      fusion outperformed "side-by-side" SPECT/CT review for anatomical localization
      and diagnostic confidence of infectious/inflammatory abnormalities. Therefore,
      SPECT/CT fusion potentially influences clinical decisions and treatment options.

PMID- 17538283
TI  - [18F]fluorodeoxyglucose positron emission tomography imaging in a case of
      relapsing polychondritis.
AB  - Relapsing polychondritis is a rare multisystemic disease that is characterized by
      recurrent inflammation of the cartilaginous structures of the external ear, nose,
      joint, larynx, and tracheobronchial tree. Airway involvement is present in up to
      50% of patients with the disease and is a major cause of morbidity and mortality.
      We describe a patient with relapsing polychondritis presenting with tracheal and
      bronchial abnormalities that were identified by an increased uptake on
      [18F]fluorodeoxyglucose positron emission tomography.

PMID- 17538284
TI  - Quantitative assessment of peripheral airway obstruction on paired
      expiratory/inspiratory thin-section computed tomography in chronic obstructive
      pulmonary disease with emphysema.
AB  - OBJECTIVES: We examined the hypothesis that paired inspiratory/expiratory
      computed tomography (CT) scans in a limited-lung area that excludes emphysema may
      provide a more accurate evaluation of peripheral airway obstruction in patients
      with chronic obstructive pulmonary disease (COPD) with emphysema. MATERIALS AND
      METHODS: This study included 32 patients with COPD. The cross-sectional area
      between -500 and -1024 HU was segmented as whole-lung. The relative areas (RA)
      less than -950 HU for the whole-lung (RA<-950) were segmented as emphysema, and
      pixels less than -900 HU for the whole-lung (RA<-900) were segmented to evaluate
      air trapping. Next, the cross-sectional area between -500 and -950 HU that
      excludes emphysema was segmented as limited-lung, and pixels between -900 and 
      950 HU for the limited-lung (RA900-950) were segmented. The changes in RA<-900
      (RA<-900-change) and RA900-950 (RA900-950-change) between inspiration and
      expiration were calculated. Correlations between CT measurements and the results
      of pulmonary function tests (PFT) were evaluated. RESULTS: There was no
      significant difference between the mean inspiratory RA<-950 and expiratory RA<
      950 (P = 0.245), but the mean expiratory RA900-950 decreased significantly
      compared with the mean inspiratory RA900-950 (P < 0.001). The correlation
      coefficients between PFT parameters and the RA900-900-change in the limited-lung
      without emphysema were higher than that of the RA<-900-change in the whole-lung.
      CONCLUSIONS: The paired inspiratory/expiratory CT measurements in the limited
      lung without emphysema correlated more closely with the PFTs. Our observations
      suggest that paired inspiratory/expiratory CT scans in the limited-lung excluding
      emphysema are sensitive for the evaluation of airway obstruction in COPD with
      emphysema.

PMID- 17538285
TI  - Computed tomographic features of pulmonary septic emboli: comparison of causative
      microorganisms.
AB  - OBJECTIVE: To describe and compare the computed tomographic (CT) findings of
      pulmonary septic emboli in causative microorganisms. METHODS: The CT findings of
      16 patients (8 men and 8 women; age range, 17 to 80 years; mean, 53.1 years) with
      documented pulmonary septic emboli were retrospectively reviewed by 2
      radiologists; their decisions on the findings were reached by consensus.
      Statistical analysis was performed using the t test and the chi test. RESULTS: A
      total of 197 peripheral nodules were seen in 6 gram-positive (n = 88) and 10 gram
      negative (n = 109) septic pulmonary emboli patients, respectively. The sizes of
      the nodules (15.94 mm; range, 3-46 mm) in gram-positive septic emboli were larger
      than those (12.29 mm; range, 4-44 mm) in gram-negative septic emboli (P = 0.006).
      Cavitation (n = 30 [34%] vs n = 23 [21%]; P = 0.041) and air bronchogram (n = 12
      [14%] vs n = 4 [4%]; P = 0.008) within the nodules were more commonly seen in
      gram-positive septic emboli. A ground-glass attenuation halo around a nodule (n =
      69 [63%] vs n = 32 [36%]; P = 0.000) and feeding vessel signs (n = 56 [51%] vs n
      = 25 [28%]; P = 0.001) were more commonly seen in gram-negative septic emboli.
      Wedge-shaped peripheral lesions abutting the pleura were seen in 4 gram-positive
      (67%) and in 1 gram-negative (10%) septic emboli patients, respectively (P =
      0.047). CONCLUSIONS: The detailed CT characteristics of peripheral nodules in
      pulmonary septic emboli may be able to differentiate the causative microorganisms
      and to provide additional information regarding treatment plans in patients with
      sepsis.

PMID- 17538286
TI  - Hybrid PET/CT of the thorax: when is computer registration necessary?
AB  - OBJECTIVE: To determine if computer registration improves the image fusion of
      hybrid positron emission tomography (PET)/computed tomography (CT) data sets in
      the thorax acquired during different breathing maneuvers. METHODS: Hybrid PET/CT
      scans were acquired with varying CT respiratory instructions. The scans of 64
      patients with 5 different breathing maneuvers were reviewed, including
      expiration, suspended breath hold, quiet breathing, small breath in, and regular
      breath in. The PET/CT data sets were reviewed before registration, after linear
      registration, and combined linear/nonlinear registration. Each PET/CT data set
      was graded for the quality of alignment at 5 anatomical locations (diaphragm,
      aortic arch, heart, thoracic spine, and lung apices) and rated from 1 (very poor)
      to 5 (excellent). The Kruskal-Wallis test was used to compare alignment between
      the breathing protocols, and Wilcoxon signed rank test was used to compare the
      registration techniques. RESULTS: The quality of anatomical alignment between
      superimposed (nonregistered) PET and attenuation correction CT (CTAC) acquired
      during expiration, suspended breath hold, and quiet breathing was excellent, with
      no significant changes in alignment following registration. The quality of
      anatomical alignment between superimposed (nonregistered) PET and CTAC acquired
      during inspiration showed significant misalignment at the heart (P = 0.001, P <
      0.0001) and diaphragm (P = 0.0001, P < 0.0001) which did not correct with linear
      registration. Alignment significantly improved with additional nonlinear
      registration at the diaphragm (P = 0.008, P = 0.0002), although cardiac
      misalignment remained. CONCLUSIONS: With hybrid PET/CT, excellent anatomical
      alignment between PET and CTAC scans can be achieved with CT acquisition during
      expiration, suspended breath hold, or quiet breathing, and additional software
      registration is not necessary. Nonlinear registration significantly improves
      alignment discrepancies at the diaphragm if inspiratory methods are used,
      however, cardiac misalignment remains.

PMID- 17538287
TI  - Pulmonary computed tomography findings of visceral larva migrans caused by
      Ascaris suum.
AB  - OBJECTIVE: To retrospectively evaluate the computed tomography (CT) findings of
      pulmonary involvement in patients with visceral larva migrans caused by Ascaris
      suum. METHODS: Institutional review board approval was obtained, and informed
      consent was waived. Chest CT scans obtained between January 1994 and November
      2005 in 32 patients infected with A. suum were retrospectively evaluated by 3
      chest radiologists. In 4 patients who underwent surgical or transbronchial
      biopsy, comparisons of the CT images with the actual specimens were performed.
      RESULTS: On CT scans, abnormal findings were seen in 28 patients. The most common
      abnormality consisted of nodules (n = 19) in which the majority had a halo of
      ground-glass attenuation (n = 17), followed by ground-glass attenuation (n = 18),
      and interlobular septal thickening (n = 14). These abnormalities were
      predominantly seen in the peripheral lung (n = 25). Of the 7 patients who
      underwent follow-up CT scans, nodules (n = 6) and ground-glass attenuation (n =
      5) had migrated in 4 patients. Pathologically, these findings corresponded to
      marked eosinophilic infiltration into the interstitium. CONCLUSIONS: These CT
      findings are considered to be suggestive of thoracic involvement in patients with
      visceral larva migrans caused by A. suum.

PMID- 17538288
TI  - Ultrasmall intrapulmonary lymph node: usual high-resolution computed tomographic
      findings with histopathologic correlation.
AB  - OBJECTIVE: To clarify high-resolution computed tomographic findings of ultrasmall
      intrapulmonary lymph node (IPLN) with histopathologic correlation. METHODS:
      Fourteen IPLNs 3 to 6 mm in diameter were identified in 7 lobectomy specimens.
      Preoperative multidetector-row, high-resolution computed tomography covering the
      whole lobe was evaluated and compared with histopathologic findings. RESULTS:
      Thirteen of 14 nodules appeared as well-defined solid nodules. The shape was
      polygonal or angular in 11 and round or oval in 3. Thirteen of 14 nodules were
      located within 15 mm of pleura. All 11 nodules apart from pleura were accompanied
      with linear opacity contiguous with pleura. Ten of 14 nodules were adjacent to
      peripheral pulmonary veins, and 4 were adjacent to linear opacity from pulmonary
      veins. These findings were confirmed pathologically, and linear opacities were
      consistent with thickened or normal interlobular septa. CONCLUSIONS: Ultrasmall
      IPLN has usual high-resolution computed tomographic findings reflecting
      histopathologic findings.

PMID- 17538289
TI  - Assessment of coronary stent in vitro on multislice computed tomography
      angiography: improved in-stent visibility by the use of 140-kV tube voltage.
AB  - OBJECTIVE: To assess the effect of tube voltage on the in-stent visibility of
      coronary stents in vitro on computed tomography (CT) angiography. METHODS: A
      total of 6 vascular models (3 models without stenosis and 3 with stenosis) using
      3 kinds of stent (Bx Velocity, Express2, and Driver) with an inner diameter of
      approximately 3.5 mm and filled with contrast material (CT attenuation, 450
      Hounsfield units) were scanned by means of a 16-detector row CT. We assessed the
      visual stenosis evaluation and inhomogeneity of stent lumen in 4 orientations (0
      , 30-, 60-, and 90-degree angles) relative to the z-axis of the scanner using 3
      imaging techniques (120-kV tube voltage using a medium convolution kernel, 120-kV
      tube voltage using a convolution kernel for bone, and 140-kV tube voltage using a
      convolution kernel for bone). Statistical analysis involved F test with a
      statistical significance of P < 0.05. RESULTS: The convolution kernel for bone
      made it easier to evaluate the stenosis inside the stents, although it increased
      the luminal inhomogeneity significantly (Bx Velocity and Express2, P < 0.005;
      Driver, P < 0.05). The luminal inhomogeneity tended to increase as the strut
      diameter and the weight per unit length increased. Using 120-kV tube voltage, the
      luminal inhomogeneity inside the stents was at the minimum in the angle of 0
      degree relative to the z-axis, and at the maximum in the angle of 90 degrees,
      except for Driver. The 140-kV tube voltage was effective for the improvement of
      luminal inhomogeneity and visibility of in-stent stenosis compared with the 120
      kV tube voltage. CONCLUSIONS: The in-stent visibility of coronary stents on CT
      angiography can be improved by the use of 140-kV tube voltage with the
      convolution kernel for bone.

PMID- 17538290
TI  - Multidetector-row computed tomographic angiography of thoracic and abdominal
      aortic aneurysms: comparison of arterial enhancement with 3 different doses of
      contrast material.
AB  - OBJECTIVE: To compare the quality of multidetector-row computed tomographic
      angiography in patients with and without aortic aneurysms by 3 different amounts
      of contrast media (CM). METHODS: A total of 115 patients with aortic aneurysms
      were divided into 3 groups: group A, 100 mL CM; group B, 75 mL CM with 20 mL
      saline flush (SF); and group C, 50 mL CM with 20 mL SF. Twenty-five patients
      without aortic aneurysms were also enrolled (group D, 50 mL CM with 20 mL SF).
      Quantitative and qualitative analyses were performed by measuring attenuation in
      thoracoabdominal/aortoiliac lumen, aneurysmal lumen, and superior vena cava.
      RESULTS: In group C, attenuation was lower in distal than those in proximal and
      middle areas (P < 0.05). Contrast enhancement in abdominal aneurysmal lumen was
      more inhomogeneous in group C (P = 0.003). Visual analysis showed contrast
      enhancement was more nonuniform in group C (P = 0.004), and perivenous artifacts
      were more conspicuous in group A (P < 0.0001). CONCLUSIONS: Seventy-five
      milliliters CM followed by 20 mL SF can produce optimal contrast enhancement at
      systemic multidetector-row computed tomographic angiography in patients with
      aortic aneurysms.

PMID- 17538291
TI  - Cardiac magnetic resonance imaging using an open 0.35 T system.
AB  - OBJECTIVE: To evaluate cardiac magnetic resonance imaging (MRI) using a 0.35 T
      magnetic resonance system with open design. METHODS: Eleven patients were
      examined in an open MRI system with a field strength of 0.35 T. Myocardial
      function was assessed with cine true fast imaging with steady-state precession
      sequences in 2 planes. Perfusion images were acquired with a T1-weighted gradient
      echo sequence. Late enhancement was performed using an inversion recovery
      prepared fast gradient echo technique. Image quality was assessed using a 4-point
      score in consensus. Signal-noise ratio was measured. RESULTS: For functional
      imaging, average score was 1.65 (SD, 0.6). For perfusion imaging, the value was
      2.25 (SD, 0.68). For late enhancement, quality score was 2.6 (SD, 0.82). Average
      value of signal-noise ratio for functional, perfusion, and late enhancement
      imaging was 50.6 (SD, 16.4), 91.8 (SD, 52.8), and 33.2 (SD, 20.4), respectively.
      CONCLUSIONS: Open MRI with lower field strength can be used for functional
      imaging of the heart. For perfusion and viability imaging (late enhancement),
      higher field strength is needed. Open low-field cardiac MRI may provide a helpful
      alternative for obese or claustrophobic patients or patients who are difficult to
      move.

PMID- 17538292
TI  - Acute and chronic complications of aortic intramural hematoma on follow-up
      computed tomography: incidence and predictor analysis.
AB  - OBJECTIVE: To ascertain the incidence of acute and chronic complications of
      aortic intramural hematoma (IMH) and to analyze the predictors of the development
      of each complication. MATERIALS AND METHODS: This retrospective study includes
      107 consecutive patients diagnosed with aortic IMH by means of computed
      tomography (CT) during the period from January 1998 to December 2003 and followed
      up with serial CT examinations (median follow-up period, 320 days). There were 36
      patients with type A and 71 with type B IMH. Initial and follow-up CT scans were
      reviewed, with special attention given to the development of complications, such
      as increase in the thickness of IMH, clinical and hemodynamic evolution requiring
      urgent surgery, and development of aortic dissection and/or aneurysm. If each
      complication developed within 30 days after the initial episode, we classified it
      as an acute complication; the others were classified as chronic complications.
      The time interval between the initial and the subsequent CT examination showing
      each complication was recorded. To identify the predictors of each complication,
      we analyzed the demographic and CT findings with regard to the following factors:
      age, sex, maximum thickness of the hematoma, maximum aortic diameter on initial
      CT examination, ulcerlike projection (ULP) on initial and follow-up CT
      examinations, and the degree of atherosclerosis. The Cox proportional hazards
      regression model with stepwise multivariate analyses was used to determine the
      significant predictors of each complication. RESULTS: Sixteen patients had acute
      complications consisting of aortic dissection (n = 7), aortic aneurysm (n = 6),
      and acute clinical and hemodynamic evolution requiring operation (n = 3). Three
      additional patients with aortic dissection (n = 1) and aneurysm (n = 2) underwent
      emergency surgery. Twenty-three patients with chronic complications had aortic
      dissection (n = 3), and aortic aneurysm (n = 20). Cox proportional hazards
      regression model revealed that the maximal diameter of involved aorta is the only
      significant predictor of the development of acute complications (P = 0.006),
      whereas the age (P = 0.040), type A IMH (P = 0.015), presence of ULP (P = 0.015),
      and newly developed ULP as revealed on follow-up CT examination (P = 0.032) were
      significant predictors of the development of chronic complications. With regard
      to the aortic dissection in 10 patients (9.3%; type A/B ratio, 5:5; median time
      interval, 34 days), Cox proportional hazards regression model revealed that the
      maximal thickness of the hematoma is the only significant predictor (P = 0.018).
      Twenty-one saccular and 5 fusiform aneurysms (24.3%) developed, as revealed on
      follow-up CT examinations (median time interval, 180 days). The presence of ULP
      (P = 0.030), type A (P = 0.038) and the maximal thickness of the hematoma (P =
      0.017) were significant predictors for the development of an aneurysm.
      CONCLUSIONS: The maximum thickness of a hematoma on the initial CT is the
      significant factor predicting the development of aortic dissection and aortic
      aneurysm. Patients with type A IMH and ULP, as revealed by initial and short-term
      follow-up CT examinations, should be carefully followed up with subsequent CT
      examination to monitor the development of an aortic aneurysm, which is a
      relatively common chronic complication of IMH.

PMID- 17538293
TI  - New approach to noninvasive coronary angiography by multidetector computed
      tomography: initial experience using gadolinium.
AB  - OBJECTIVE: To investigate the gadolinium performance for 16-detector-row coronary
      computed tomography (CT) angiography. METHODS: Ethics committee approval and
      informed consent were obtained. Ten patients with coronary artery disease
      underwent digital coronary angiography and gadolinium-enhanced CT coronary
      angiography (Gd-CTCA) within the same week. For the Gd-CTCA, each patient
      received a dose of 0.3 mmol/kg of body weight of 0.5 mmol/mL gadoterate
      meglumine. Two readers interpreted the CT angiographies independently, and their
      results were matched with the digital angiography findings. The diagnostic
      accuracy of Gd-CTCA was calculated by the exact binomial method. RESULTS:
      Sensitivity, specificity, and positive and negative predictive values were for
      observer 1: 91.67%, 98.73%, 84.62%, and 99.36%, and for observer 2: 83.33%,
      98.73%, 83.33%, and 98.73%, respectively. CONCLUSION: Preliminary results
      demonstrated that gadolinium chelates may be used as an alternative CT contrast
      media in coronary CT angiographies, without detriment to diagnosis results.

PMID- 17538294
TI  - High-resolution reconstruction of a waxed heart specimen with flat panel volume
      computed tomography and rapid prototyping.
AB  - A waxed piglet heart was scanned with a flat panel volume computed tomography
      scanner (voxel size, 0.25 mm). Virtual and real laser-sintered models showed
      excellent visual concordance with the original. Using an iterative-closest-point
      algorithm, a very low mean surface distance was found between the original and
      laser-sintered model (0.26 +/- 0.34 mm). These techniques allow submillimeter 3
      dimensional virtual and real reconstructions without destroying the original and
      might be useful for teaching, research, and planning of cardiac interventions.

PMID- 17538295
TI  - Diffusion-weighted imaging of the prostate at 3 T for differentiation of
      malignant and benign tissue in transition and peripheral zones: preliminary
      results.
AB  - OBJECTIVE: To evaluate prospectively the use of apparent diffusion coefficients
      (ADCs) for the differentiation of malignant and benign tissue in the transition
      (TZ) and peripheral (PZ) zones of the prostate diffusion-weighted imaging (DWI)
      at 3 T magnetic resonance imaging (MRI) using a phased-array coil. METHODS: The
      DWI at 3-T MRI was performed on a total of 35 patients before radical
      prostatectomy. A single-shot echo-planar imaging DWI technique with b = 0 and b =
      1000 s/mm2 was used. The ADC values were measured in both benign and malignant
      tissues in the PZ and TZ using regions of interest. Differences between PZ and TZ
      ADC values were estimated using a paired Student t test. Presumed ADC cutoff
      values in the PZ and TZ for the diagnosis of cancer were assessed by receiver
      operating characteristic analysis. RESULTS: The ADC values of malignant tissues
      were significantly lower than those of benign tissues in the PZ and TZ (P <
      0.001; 1.32 +/- 0.24 x 10(-3) mm2/s vs 1.97 +/- 0.25 x 10(-3) mm2/s, and 1.37 +/-
      0.29 x 10(-3) mm2/s vs 1.79 +/- 0.19 x 10(-3) mm2/s, respectively). For tumor
      diagnosis, cutoff values of 1.67 x 10(-3) mm2/s (PZ) and 1.61 x 10(-3) mm2/s (TZ)
      resulted in sensitivities and specificities of 94% and 91% and 90% and 84%,
      respectively. CONCLUSIONS: The DWI of the prostate at 3T MRI using a phased-array
      coil was useful for the differentiation of malignant and benign tissues in the TZ
      and PZ.

PMID- 17538296
TI  - Differentiating malignant from benign wall thickening in postoperative stomach
      using helical computed tomography: results of multivariate analysis.
AB  - OBJECTIVE: To determine significant computed tomography (CT) predictors for
      differentiating malignant from benign wall thickening in postoperative stomach.
      METHODS: Sixty-nine patients with perianastomotic wall thickening (25 malignant,
      44 benign) after gastric surgery were identified. All patients underwent contrast
      enhanced CT with the administration of oral contrast agents such as air, diluted
      barium, or water. Two radiologists analyzed CT images regarding enhancement of
      thickened wall, obliteration of wall layering, heterogeneity, asymmetry,
      perigastric infiltration, proximity to metallic suture material, lymphadenopathy,
      adjacent bowel thickening, and periceliac soft-tissue density. Another
      radiologist measured the wall thickness and the mean CT value of the lesion and
      normal mucosa. Individual CT findings relevant as predictors were determined
      using the univariate test. Multivariate analysis was used to determine the most
      predictable factors. RESULTS: Malignant wall thickening was significantly thicker
      than benign one. Isoattenuation and high attenuation of thickened wall were more
      frequently seen in malignant than in benign cases. Multivariate analysis showed
      that isoattenuation or high attenuation of thickened wall, proximity to suture
      material, and perigastric infiltration were only 3 variables that independently
      differentiated malignant from benign thickening in postoperative stomach.
      CONCLUSION: Isoattenuation or high attenuation of thickened wall, perigastric
      infiltration, and wall thickening without metallic suture material are the 3 main
      factors distinguishing malignant from benign thickening in postoperative stomach.

PMID- 17538297
TI  - Magnetic resonance imaging of typical polypoid adenomyoma of the uterus in 8
      patients: correlation with pathological findings.
AB  - OBJECTIVE: To study the magnetic resonance imaging findings of typical polypoid
      adenomyoma and correlate radiological findings with histopathologic findings.
      METHODS: Magnetic resonance imaging and histopathologic findings were
      retrospectively reviewed in 8 patients. The size, location, polyp's shape, and
      signal intensity of magnetic resonance imaging findings were evaluated. RESULTS:
      The polyp's shape of 8 cases is pedunculated in 7 and sessile in 1, and all 8
      cases are well circumscribed. Four cases (50%) show an isointense mass relative
      to the myometrium with small or large hyperintense foci on T1-weighted imaging
      (T1WI) or T2-weighted imaging (T2WI), reflecting the fascicle of smooth muscle
      with islands of hemorrhagic endometrial tissue. One case forms a large
      hemorrhagic cavity, being hyperintense on T1WI and hypointense on T2WI. Three
      cases (37%) show almost homogeneous isointense or hyperintense mass on T2WI.
      CONCLUSIONS: When there is a well-defined polypoid mass protrusion into the
      uterine endometrial cavity that is isointense relative to the myometrium with
      small or large foci of high signal on T1WI or T2WI in a premenopausal woman,
      typical polypoid adenomyoma can be considered in the differential diagnosis.

PMID- 17538298
TI  - Evaluation of the longitudinal tumor extent of bile duct cancer: value of adding
      gadolinium-enhanced dynamic imaging to unenhanced images and magnetic resonance
      cholangiography.
AB  - OBJECTIVE: To determine the added value of gadolinium-enhanced dynamic magnetic
      resonance (MR) images compared with unenhanced and MR cholangiography (MRC)
      images, to evaluate the longitudinal extension of bile duct cancer. MATERIALS AND
      METHOD: Thirty-three patients with hilar cholangiocarcinoma or common duct cancer
      who had undergone MRC, unenhanced, and gadolinium-enhanced dynamic MR images and
      surgery were included in this study. Two experienced radiologists independently
      reviewed 2 image sets in 2 steps, that is, the MRC set (unenhanced and MRC) and
      the combined image set (MRC set with dynamic images). At each step, the readers
      determined the tumor status according to the Bismuth-Corlette classification. The
      readers assigned their confidence levels on a 5-point scale regarding whether the
      tumor involved the secondary confluence of the bile duct and the intrapancreatic
      common bile duct. The radiologists' diagnostic confidence of the 2 image sets was
      analyzed using receiver operating characteristic analysis. RESULTS: Receiver
      operating characteristic analysis showed higher areas under the curve values when
      the combined image set was interpreted (0.990 +/- 0.017 for reader 1 and 0.951 +/
      0.027 for reader 2) than when the MRC set was interpreted (0.982 +/- 0.017 for
      reader 1 and 0.902 +/- 0.038 for reader 2); however, the difference was not
      statistically significant for either reader (P > 0.05). In addition, regarding
      evaluation of the tumor status according to the Bismuth-Corlette classification,
      the overall accuracy was higher for the combined image set than for the MRC set
      alone, but the difference was not significant (P > 0.05). When dynamic images
      were added to the MRC images, interobserver agreement improved from 0.72 to 0.84.
      CONCLUSIONS: The addition of contrast-enhanced dynamic images to unenhanced and
      MRC images did not significantly improve the diagnostic accuracy for assessment
      of the longitudinal extent of bile duct cancer.

PMID- 17538299
TI  - Reappraisal of right portal segmental ramification based on 3-dimensional volume
      rendering of computed tomography during arterial portography.
AB  - OBJECTIVE: To investigate and describe the segmental ramification patterns of the
      right portal vein (RPV) according to the Couinaud system. MATERIALS AND METHODS:
      Between February 2004 and June 2005, 127 patients with hepatic tumors underwent
      computed tomography during arterial portography with a 16-slice multidetector
      computed tomography. The final analysis included 90 patients without RPV
      thrombosis or obvious vascular distortion. The ramification patterns of RPV were
      verified by 3-dimensional portograms using volume-rendering technique. RESULTS:
      Seventy-five patients (83.3%) had bifurcation of the main portal vein, 12 (13.3%)
      had trifurcation, and 3 (3.3%) had the right posterior portal vein (RPPV) arising
      from main portal vein. A total of 5 segmental types and 3 subsegmental subgroups
      of RPV ramification patterns were clarified: type I, the classic ramification
      pattern with right anterior portal vein (RAPV) branching to S8/S5 and RPPV
      branching to S7/S6 (63; 70%); II, two separate segmental branches to S7 and S6
      without a definite main stem of RPPV (18; 20%); III, "whisk-like" ramification
      pattern of RPV (2; 2.2%); IV, RAPV branching to S8 alone and RPPV to S5, S6, and
      S7, consecutively (5; 5.6%); and V, RPV first branching to S8/S5 and then to
      S7/S6 after a common path (2; 2.2%); subgroup a with dorsocranially directed
      branches arising from P8 and supplying S8 posterior to the right hepatic vein
      (28; 31.1%); subgroup b with RPPV branching to the dorsal part of S5 (11; 12.2%);
      and subgroup a + b, combination of the aforementioned 2 subgroups (45; 50%). In
      most patients, RAPV had dorsocranially directed branches posterior to the right
      hepatic vein (73; 81.1%), and RPPV gave off branches to the dorsal part of S5
      (56; 62.2%). CONCLUSIONS: Recognition of these ramification patterns could be
      helpful for more accurate anatomical resection of right hemiliver and
      preoperative planning, although some variants are present.

PMID- 17538300
TI  - Bilateral renal artery entrapment by diaphragmatic crura: a rare cause of
      renovascular hypertension with a specific management.
AB  - We present the case of a young man with compression of both renal arteries by the
      crura of the diaphragm. Correct diagnosis of renal artery entrapment is difficult
      but crucial. The investigations rely on an high index of suspicion and include
      Doppler ultrasound and spiral computed tomography angiography, which permits
      visualization of the diaphragm and its relationships with the aorta. This
      pathology, unlike common renal artery stenoses, requires surgical decompression
      and sometimes aortorenal bypass graft.

PMID- 17538301
TI  - Small cell carcinoma of the uterine corpus: MR imaging and pathological
      correlation.
AB  - Small cell carcinoma of the uterine corpus is a rare but aggressive neoplasm
      showing neuroendocrine differentiation; its radiological findings are not well
      described. We report the magnetic resonance features of 3 cases with pathological
      correlation. Small cell carcinoma is shown as a bulky endometrial tumor of
      heterogeneous appearance on T2-weighted images, frequently associated with
      diffuse myometrium invasion and early extrauterine spread. Irregular enhancement
      with multifocal unenhanced areas of the thickened myometrium on contrast-enhanced
      T1-weighted images may represent the infiltrative nature of the tumor with
      extensive necrosis.

PMID- 17538302
TI  - Serous psammocarcinoma of the ovary: CT and MR findings.
AB  - Serous psammocarcinoma, a rare variant of ovarian serous carcinoma, is
      characterized histologically by the pervasive presence of psammoma bodies. In
      this case, computed tomography scans showed extensively calcified pelvic and
      peritoneal masses. The pelvic mass appeared sandy on enhanced T1-weighted
      magnetic resonance images. These imaging results suggest that the presence of
      abundant psammomatous calcifications in primary and disseminated lesions may be a
      radiological marker of ovarian psammocarcinoma.

PMID- 17538304
TI  - Strabismus in unicoronal synostosis: ipsilateral or contralateral?
AB  - Unicoronal synostosis is a premature fusion of one of the coronal sutures and is
      thought to carry an increased prevalence for strabismus. Studies suggest the
      nature of the strabismus to be a hypertropia occurring ipsilateral to the fused
      coronal suture. The aim of this study is to investigate the laterality of
      strabismus in unicoronal synostosis and report on ocular motility and refractive
      findings in a large, unbiased sample group. A retrospective case study analysis
      was carried out on 59 patients with a confirmed diagnosis of unicoronal
      synostosis referred to the Oxford Craniofacial Unit over a 14 year period.
      Manifest strabismus in the primary position was found in 34 (57.6%) cases. In 19
      (55.9%) cases, this occurred contralateral to the fused suture, and in 9 (26.5%)
      cases, strabismus was on the ipsilateral side. Six had alternating strabismus.
      These results are contrary with apparent findings in the literature but are not
      statistically significant (P = 0.0872) for strabismus occurring more frequently
      on the nonsynostotic side. Esotropia with a vertical component was most common,
      found in 61% of all cases with strabismus. Apparent inferior oblique overaction
      was found in 30 of the 59 (50.8%) cases, with this occurring bilaterally in 14
      cases. Significant refractive error was found in 46% of all cases, most of which
      showed anisometropia and astigmatism that occurred more frequently on the
      contralateral, nonsynostotic side (P = 0.0106). All cases of unicoronal
      synostosis with a mutation of the FGFR2 or FGFR3 gene had manifest strabismus.
      Manifest strabismus was found in 57.6% of cases reviewed, but this was found to
      be no more likely to occur on the side contralateral or ipsilateral to the fused
      suture (P = 0.0872). Anisometropia and astigmatism were found more frequently in
      the eye contralateral to the fused suture.

PMID- 17538305
TI  - Describing normal variations of head and face by using standard measurement and
      craniofacial variability index (CVI) in seven-year-old normal children.
AB  - To define the line separating normal from abnormal craniofacial appearance is
      complex and difficult because there are many craniofacial measurement parameters,
      and there are also many factors that influence the craniofacial morphology, such
      as genetics and environmental influence. The aim of this study is to define the
      range of normal distribution of craniofacial morphology by using different
      numerical methods in seven-year-old students in Denizli, Turkey. For this
      purpose, height, weight and 20 defined craniofacial parameters (including face
      height, face width, face depth, eyes, nose, ear, mouth and head) of 61 female and
      58 male (119 total) normal cases were measured. Every measurement was taken twice
      by the same investigator and the standard anthropometric methods of measurements
      were used. All data were recorded by computer and analyzed statistically. At the
      end, craniofacial variability index (CVI) was found 0.874 +/- 0.338 in female,
      0.824 +/- 0.333 in male. Furthermore, the female results were compared to the
      male results. Parameters were correlated with each other. Seven years old is the
      beginning age for primary school in Turkey. So, it is an important year for
      initial diagnostic screening in children with facial syndromes, and it is also
      important for pre-and postsurgical assessments of children with craniofacial
      anomalies.

PMID- 17538306
TI  - Peripheral nerve regeneration using a three dimensionally cultured schwann cell
      conduit.
AB  - The use of artificial nerve conduit containing viable Schwann cells is one of the
      most promising strategies to repair peripheral nerve injury. To fabricate an
      effective nerve conduit whose microstructure and internal environment are more
      favorable in nerve regeneration than those currently existing, a new three
      dimensional (3D) Schwann cell culture technique using Matrigel and dorsal root
      ganglion (DRG) was developed. Nerve conduit of 3D arranged Schwann cells was
      fabricated using direct seeding of freshly harvested DRG into Matrigel-filled
      silicone tubes (inner diameter 1.98 mm, 14 mm length) and in vitro rafting
      culture for 2 weeks. The nerve regeneration efficacy of 3D cultured Schwann cell
      conduit (3D conduit group, n = 6) was assessed using an Sprague-Dawley rat
      sciatic nerve defect of 10 mm and compared with that of a silicone conduit filled
      with Matrigel and Schwann cells prepared with the conventional plain culture
      method (two-dimensional [2D] conduit group, n = 6). After 12 weeks, sciatic
      function was evaluated with sciatic function index (SFI) and gait analysis, and
      histomorphology of nerve conduit and the innervated tissues of sciatic nerve were
      examined using image analyzer and electromicroscopic methods. The SFI and ankle
      stance angle in the functional evaluation were -60.1 +/- 13.9, 37.9 degrees +/-
      5.4 degrees in the 3D conduit group (n = 5) and -87.0 +/- 12.9, 32.2 degrees +/-
      4.8 degrees in the 2D conduit group (n = 4). The myelinated axon was 44.91% +/-
      0.13% in the 3D conduit group and 13.05% +/- 1.95% in the 2D conduit group. In
      the transmission electron microscope study, the 3D conduit group showed more
      abundant myelinated nerve fibers with well-organized and thickened extracellular
      collagen than the 2D conduit group, and the gastrocnemius muscle and biceps
      femoris tendon in the 3D conduit group were less atrophied and showed decreased
      fibrosis with less fatty infiltration than the 2D conduit group. A new 3D Schwann
      cell culture technique was established, and nerve conduit fabricated using this
      technique showed much improved nerve regeneration capacity than the silicone tube
      filled with Matrigel and Schwann cells prepared from the conventional plain
      culture method.

PMID- 17538307
TI  - Role of maxillofacial surgery in patients with neurofibromatosis type I.
AB  - Neurofibromas are a clinical manifestation of neurofibromatos is type I (NF1).
      Management of these tumors remains a challenge for the clinician. The goal of the
      present study is to point out treatment guidelines for these lesions. Eighteen
      patients diagnosed with NF1 and presenting lesions of the craniomaxillofacial
      district were included in the study. On the basis of clinical evidence and
      patient's expectations, only six patients of this group underwent surgery. All
      patients that had no surgery were included in a follow-up protocol to evaluate
      progression of disease. Four patients who underwent surgery had good
      functional/aesthetic results, whereas two patients had incomplete rehabilitation.

PMID- 17538308
TI  - Bone regeneration in athymic calvarial defects with Accell DBM100.
AB  - Bioimplants containing bone morphogenetic proteins (BMP) such as demineralized
      bone matrix (DBM) are used clinically to repair bone defects because of their
      ability to stimulate bone regeneration. Because of handling issues, DBM granules
      are often combined with an inert carrier, which reduces the DBM content to 40% or
      less by volume. Recently, Accell DBM100 (Accell, IsoTis OrthoBiologics, Irvine,
      CA) has been developed, which uses processed DBM as the carrier, resulting in a
      DBM content of 100%. The purpose of this investigation was to evaluate the use of
      Accell for bone defect healing.Forty-two athymic male rats were divided into
      three groups. Bilateral 5 mm calvarial defects were created in each animal. In
      group 1, one defect was filled with Accell and the other defect was left unfilled
      (control). In group 2, one defect was filled with OP-1 putty (recombinant human
      BMP-7 and type I collagen), and the other was left unfilled. In group 3, one
      defect was filled with Accell and the other with OP-1. Animals were sacrificed at
      4 and 8 weeks, postoperatively. Specimens were analyzed by histomorphometry to
      evaluate bone regeneration quantitatively. Accell and OP-1 both induced
      significantly more bone at 4 and 8 weeks compared with the unfilled contralateral
      defects. OP-1-filled defects produced significantly more total reparative tissue
      (bone + marrow) compared with Accell (P < 0.01); however, the increase in new
      bone did not reach significance at either time (P = 0.06 at 4 wk; P = 0.10 at 8
      wk). In conclusion, these results suggest that Accell DBM100 will be useful in
      repairing craniofacial bone defects clinically.

PMID- 17538309
TI  - Modeling of scaphocephaly using superelastic titanium-nickel rings: a preliminary
      report.
AB  - As long as resection of sagittal suture eliminates craniostenosis it leads to
      desired cranium broadening and shortening solely in the case of children under
      six months of age. In the majority of cases, especially in older children, boat
      shaped cranium remains rather unchanged and its effective modeling requires
      extensive dissection and osteotomy of the whole cranium vault (e.g., frontal,
      occipital and parietal bones). Lauritzen's method is an alternative solution. It
      consists of distraction of cranium vault bones with the aid of steel springs. In
      order to simplify and improve the efficacy of treatment since 2002, the authors
      originated the application of titanium-nickel rings to model the cranium. After
      the sparing excision of cranium vault sutures in the shape of letter "H" the
      compressed ring is given in the sagittal axis oval shape and in this form it is
      fixed to osseous margins. The ring's expansion at the same time broadens and
      shortens the cranium vault. Material was analyzed from 7 children (range, 9
      months to 4 years of age), who were treated in the years 2002-2006 because of
      sagittal craniostenosis. Observations made so far and good treatment results
      indicate purposefulness of discussed treatment continuation.

PMID- 17538310
TI  - Reconstruction of saddle nose deformity with three-dimensional costal cartilage
      graft.
AB  - Saddle nose deformity is characterized by depression of the nasal bone and the
      cartilage dorsum associated with a collapse in the upper lateral and alar
      cartilages. Etiopathogenesis usually involves trauma or invasive excision of the
      bone and cartilage. Surgical treatment for functional and aesthetic recovery
      relies on the use of grafts. Options for grafting include autogenous tissue such
      as bone or cartilage and alloplastic augmentation. Nine patients with saddle nose
      deformity underwent surgical reconstruction with autogenous costal cartilage. The
      deformity was the result of trauma in seven patients and secondary to surgery in
      two patients. Cartilage obtained from the sixth and seventh ribs was used as the
      graft material to compensate for the low nasal dorsum. Cartilage was used as a
      single unit and shaped to cover the nasal dorsum and the lateral nasal walls
      completely. The upper lateral cartilages were fixed to shaped cartilage graft.
      Additional cartilage grafts into the columella and septum were also placed in all
      patients. Functional and aesthetic outcome was satisfactory in all patients. As a
      result, using costal cartilage graft, a single unit allowed more predictable and
      reliable reconstruction of the saddle nose deformity than the conventional dorsal
      grafts.

PMID- 17538311
TI  - Reconstruction of the nasal valve.
AB  - The authors present their experience with reconstructive nasal valve surgery,
      evaluating the effects related to the use of a composite graft, which is a graft
      made of skin and cartilage, or mucosa and cartilage, and to the transposition of
      mucocartilaginous flaps. A sample of 15 patients (12 women and three men)
      selected among 452 cases treated with functional and aesthetic rhinoplasty at the
      Department of Plastic and Reconstructive Surgery of the "Tor Vergata" University
      of Rome was analyzed. Patients were between 25 and 50 years of age, with a mean
      age of 40 years, and were treated with secondary rhinoplasty for valvular
      stenosis. Of these patients, 12 had functional problems of the internal and
      external nasal valve, and three had internal valve stenosis. In our sample of 15
      patients, respiratory symptoms improved at short- and long-term follow up. In all
      cases, a good aesthetic result was obtained. The patients were not satisfied with
      the aesthetic result in only three cases as a result of enlargement or asymmetry
      of the external valvular area. In 11 cases, an "open tip" rhinoplasty was
      performed with a retroauricular skin-cartilage composite graft to correct
      internal-external valvular stenosis. In all the cases of internal valvular
      stenosis (three patients) and in one case of internal-external valvular stenosis,
      a transposition of mucocartilaginous flaps with a section of the mucosa of the
      upper lateral cartilage was performed.

PMID- 17538312
TI  - Contour restoration of the secondary deformities of zygomaticoorbital fractures
      with porous polyethylene implant.
AB  - Inappropriate treatment or untreated fractures of the zygomaticoorbital area
      results in secondary deformities such as loss of malar projection, enophthalmos,
      and dystopia. Secondary deformities can be corrected with osteotomies, contour
      restoration, or a combination of both. Contour restoration can be performed with
      using onlay grafting with autogenous material or alloplastic implants. In this
      study, mild to moderate secondary deformities of zygomaticoorbital fractures were
      corrected with porous a polyethylene implant, which is a highly biocompatible,
      durable, and stable material. The number of patients who have no surgical
      treatment at the time of their initial injury was 15, whereas the number of
      patients who have an initial treatment that resulted in secondary deformities was
      seven. Twelve of 15 patients had only loss of cheek projection and three of the
      15 patients had dystopia and loss of cheek projection. The remaining seven
      patients had secondary deformities resulting from skeletal surface contour
      abnormality as a result of comminuted fractures. In 17 of the patients, we used a
      subciliary approach while using the old incision scar for access in the
      remainder. In 22 patients, 24 implants were used. Porous polyethylene implant was
      carved outside in according to the existing contour deficit and was placed in the
      subperiosteal plane and fixed with titanium screws. The mean follow-up period was
      13 months (range, 6-24 months). In this follow-up period, there was no implant
      extrusion, exposition, infection, or any complication resulting from subciliary
      incision. Patients were satisfied with the results. The best result can be
      achieved with porous polyethylene implant in contour restoration of mild to
      moderate secondary deformities of zygomaticoorbital fractures. The use of this
      implant in the zygomaticoorbital area is safe and has minimal morbidity.

PMID- 17538313
TI  - Cranioplasty of large cranial defect at an early stage after decompressive
      craniectomy performed for severe head trauma.
AB  - Large cranial defects resulting from decompressive craniectomy performed for
      refractory intracranial hypertension after head trauma is one of the indications
      for cranioplasty, and this procedure is commonly performed 3 months after
      craniectomy. However, the large cranial defect would lead to the kinds of
      complications early during the phase of these patients' recovery, which would go
      against rehabilitation. This study retrospectively reviewed 23 patients
      undergoing early cranioplasty (5-8 weeks after craniectomy) in the last 4 years
      with a detailed choice of patients, outcome of complications after head trauma
      and large craniectomy, as well as assessment of prognosis. The early outcome (1
      month later) revealed most of the patients who had conscious disturbance before
      the cranioplasty recovered their consciousness and presented an improved
      neurologic function. The long-dated prognosis (18 months later) revealed that 17
      patients were good (independent patients) in this series (74%), whereas four
      patients survived with a severe disability (17%) and two remained in a vegetative
      state (9%). No dead patients or intracranial infection after the procedure were
      found in this study. Most patients' complications were relieved after the
      cranioplasty with improvements of symptoms or image of computed tomography scan.
      In conclusion, we consider that with the appropriate choice of patients and
      materials, early cranioplasty for large cranial defects after decompressive
      craniectomy would be safe and helpful for the improvement of patients' neurologic
      function and prognosis. To our knowledge, this series may be the first detailed
      report in English about early cranioplasty after decompressive craniectomy. We
      are going to perform prospective and retrospective contrastive studies to further
      confirm the effects of this procedure on the patients with large cranial defects
      after decompressive craniectomy.

PMID- 17538314
TI  - The use of a wax bite wafer and a double computed tomography scan procedure to
      obtain a three-dimensional augmented virtual skull model.
AB  - A detailed visualization of the interocclusal relationship is essential in a
      three-dimensional virtual planning setup for orthognathic and facial orthomorphic
      surgery. The purpose of this study was to introduce and evaluate the use of a wax
      bite wafer in combination with a double computed tomography (CT) scan procedure
      to augment the three-dimensional virtual model of the skull with a detailed
      dental surface. A total of 10 orthognathic patients were scanned after a
      standardized multislice CT scanning protocol with dose reduction with their wax
      bite wafer in place. Afterward, the impressions of the upper and lower arches and
      the wax bite wafer were scanned for each patient separately using a high
      resolution standardized multislice CT scanning protocol. Accurate fitting of the
      virtual impressions on the wax bite wafer was done with surface matching using
      iterative closest points. Consecutively, automatic rigid point-based registration
      of the wax bite wafer on the patient scan was performed to implement the digital
      virtual dental arches into the patient's skull model (Maxilim, version 2.0;
      Medicim NV, St-Niklaas, Belgium). Probability error histograms showed errors of <
      or =0.16 mm (25% percentile), < or =0.31 mm (50% percentile), and < or =0.92 (90%
      percentile) for iterative closest point surface matching. The mean registration
      error for automatic point-based registration was 0.17 +/- 0.07 mm (range, 0.12
      0.22 mm). The combination of the wax bite wafer with the double CT scan procedure
      allowed for the setup of an accurate three-dimensional virtual augmented model of
      the skull with detailed dental surface. However, from a clinical workload, data
      handling, and computational point of view, this method is too time-consuming to
      be introduced in the clinical routine.

PMID- 17538315
TI  - An experimental study of heat adaptation of bioabsorbable craniofacial meshes and
      plates.
AB  - Intraoperative heating of bioabsorbable plates and mesh panels to above the glass
      transition temperature is commonly performed to assist their adaptation to bone.
      Some studies suggest that once heat-adapted, such implants under certain
      conditions tend to partially revert to their preadapted shape, termed a "memory
      effect." We investigated this phenomenon by using heat-adapted 82:18 poly-L
      lactic acid:polyglycolic acid copolymer mesh panel and plate specimens with a
      glass transition temperature of 57 degrees C. The specimens retained limited
      malleability even at temperatures as low as 45 degrees C, substantially below the
      nominal glass transition temperature, as measured by shape relaxation
      experiments. At 40 degrees C to 42 degrees C, however, shape relaxation was not
      observed. A three-dimensional synthetic bone construct was also fixated using 90
      degrees C heat-adapted plates, then incubated in a 37 degrees C buffer bath for 4
      weeks, with periodic measurement of the shape of the construct. No changes in
      shape were recorded over this interval, suggesting that heat-adapted
      bioabsorbable implants forming a three-dimensional fixation network with multiple
      bone fragments cannot independently shape relax with the overall
      interconnectedness of the network ensuring its stability over time.

PMID- 17538316
TI  - Effect of local simvastatin application on mandibular defects.
AB  - Osteoinductive characteristics of bone grafts are important for enhancing osseous
      healing at grafted defect sites. The cholesterol-lowering drug simvastatin has
      been shown to stimulate bone formation by increasing the gene expression of bone
      morphogenetic protein-2 and vascular endothelial growth factor. The purpose of
      this study was to determine the effect of local simvastatin application on bone
      defect healing and compare the amount of new bone produced by simvastatin gelatin
      sponge graft with that produced by a gelatin sponge graft and with natural
      healing. Twenty-one bone defects at 3 mm diameter were created in the angulus
      mandible region of Wistar albino rats. In the experimental group, nine defects
      were grafted with simvastatin dissolved in water mixed with a gelatin sponge. In
      the control groups, eight defects were grafted with water mixed with a gelatin
      sponge alone (active control) and six were left empty (passive control). Animals
      were killed on day 14 and the defects were prepared for radiologic and histologic
      assessment. Density of the regenerate was evaluated by peripheral quantitative
      computed tomography. The density of the experimental group was 240% more than the
      passive control group and 190% more than the active control group (P < 0.01).
      Histologic examination also showed more new bone formation in the experimental
      group than control groups. In conclusion, the simvastatin gelatin sponge enhanced
      bone defect healing in the mandible of rats.

PMID- 17538317
TI  - Experimental study of autologous cartilage, acellular cadaveric dermis,
      lyophilized bovine pericardium, and irradiated bovine tendon: applicability to
      nasal tip plasty.
AB  - The purpose of this study was to compare the volumetric and histologic changes of
      the acellular cadaveric dermis, lyophilized bovine pericardium, irradiated bovine
      tendon, and autologous cartilage transplanted subcutaneously in the rats. Four
      different kinds of implants were placed in subcutaneous pockets of the dorsum of
      40 Wister rats. The implants with the subcutaneous pockets were retrieved in the
      first, fourth, eighth, and 12th weeks after implantation. The size and histologic
      change of each implant were observed. The xiphoid cartilage showed the peak
      survival (71.0%, P = 0.247) on the 12th week, but part of the cartilage was
      absorbed irregularly and its shape changed unpredictably. The lyophilized bovine
      pericardium had a high survival rate as well (64.4%, P = 0.016). However, the
      size decreased significantly in the first through 12th weeks. A survival of
      acellular cadaveric dermis was lower (38.8%, P = 0.036) than the cartilage and
      pericardium, but it sustained the structure for 12 weeks and changed peripherally
      into the neocollagen. Irradiated bovine tendon disclosed the lowest survival rate
      (31.4%, P = 0.008). The structure was gradually distorted and replaced entirely
      by neocollagen in the 12th week after implantation. Autologous cartilage is the
      best choice for soft tissue and nasal tip augmentation. Although other implants
      than the cartilage showed significant diminution of its volume in 12 weeks,
      lyophilized bovine pericardium could be the next substitute to the cartilage in
      soft tissue augmentation.

PMID- 17538318
TI  - Platelet-rich and platelet-poor plasma: development of an animal model to
      evaluate hemostatic efficacy.
AB  - Hemostasis is important for any surgical procedure. One method uses autologous
      platelet-rich and/or platelet-poor plasma sprayed on the wound site. Although
      effective, there are little quantitative data available to fully document the
      extent to which these autologous products function as hemostats. Also,
      limitations in current animal models make quantitative study of topical hemostats
      difficult. A porcine partial-thickness skin wound model was developed to compare
      the hemostatic ability of these treatments with untreated control wounds.
      Rectangular partial-thickness dermal wounds were created in the back of a pig,
      which was then sprayed with activated platelet-rich plasma, activated platelet
      poor plasma, or left untreated. Bleeding was quantified by two methods: 1)
      gravimetric measurement of exudate transfer to a sponge over a 15-minute
      interval, and 2) iron assay of the exudate over this same interval. Values for
      treated wounds were normalized to those of control wounds to minimize interanimal
      variability. Both gravimetric and iron assay measurements demonstrated that
      platelet-rich plasma was effective within 5 minutes after application with
      normalized bleeding values of approximately 35% and 20%, respectively, of the
      untreated controls. Corresponding values for platelet-poor plasma were
      approximately 90% and 65%, respectively, with differences only significant for
      the iron assay method measured on 10- and 15-minute wound exudate. Although both
      platelet-rich and platelet-poor plasma demonstrated hemostatic potential, the
      effect was more robust with the former. Iron assay was a more accurate method of
      measuring bleeding than gravimetric analysis.

PMID- 17538319
TI  - 'Z-pattern' craniosynostosis: a novel presentation of trisutural fusion.
AB  - The majority of infants with multiple sutural craniosynostosis have identifiable
      syndromes, which affect both coronal sutures (Apert, Crouzon, Pfeiffer, and so
      on), and multiple sutural fusions not involving both these sutures are exceeding
      rare. We report a highly unusual pattern of trisutural fusion, which to our
      knowledge has not been previously described. A retrospective clinical review was
      performed of all cases of craniosynostosis, which had presented to the
      Craniofacial Center in Dallas, over a 15-year period. Two patients were
      identified with a unique pattern of craniosynostosis involving the left coronal,
      sagittal, and right lambdoid sutures creating a "Z-pattern." Both patients were
      treated with staged cranial vault reconstructive procedures with an initial
      posterior remodeling (3 to 4 months) followed by an anterior repair (7 to 8
      months). Both patients developed cerebellar tonsillar herniation, and one
      symptomatic patient required surgical decompression. With a follow up of greater
      than 2 years, normocephaly has been maintained with growth, and both children
      appear to have normal intellectual development. A unique pattern of trisutural "Z
      patterned" craniosynostosis is presented. This distinctive pattern of
      craniosynostosis appears to be associated with cerebellar tonsillar herniation.
      In this small series, a two-staged procedure successfully normalized the
      calvarial dysmorphism, and early growth and development appear normal.

PMID- 17538320
TI  - Cutaneous distribution of zygomaticofacial nerve.
AB  - The aim of this study is to elucidate the cutaneous distribution of the
      zygomaticofacial nerve (ZFN). Twenty hemifaces of 10 adult Korean cadavers were
      dissected. ZFN-innervated limits were rectangular and each side was 18.8 +/- 4 mm
      and 15.8 +/- 3.4 mm. The center of the rectangle was located laterally at 17.3 +/
      5.5 mm from the lateral canthus and then inferiorly at 18.1 +/- 3.1 mm. The
      cutaneous area innervated by the ZFN was rectangular shaped having a horizontal
      side that was 9.3 +/- 4% to 27.3 +/- 7.5%of the line from the lateral canthus to
      the root of helix and a vertical side that was 13.9 +/- 5.8% to 35.7 +/- 5.4% of
      the line from the lateral canthus to the oral commissure level. Knowledge of ZFN
      innervation is available with an intraoral approach in maloplasty or midface
      lift.

PMID- 17538321
TI  - Intraneural topography of the extratemporal facial nerve: microsurgical nerve
      reconstruction.
AB  - The fascicular pattern is the most important component of a nerve when a
      microsurgical reconstruction is made. The intraneural topography of the
      extratemporal facial nerve does not have a reliable fascicular pattern, although
      our study in 25 extratemporal facial nerves showed a definite fascicular pattern
      in the different studied levels. The microanatomic intraneural investigation was
      made in four different levels; we studied the diameter of the trunk, number and
      diameter of each fascicle, fascicular pattern, characteristics of the epineurium,
      perineurium, and interfascicular connective tissue, and extra- and intraneural
      blood supply. In the proximal and distal facial trunk, most axons are included in
      one to three big funiculus surrounded by a small amount of connective,
      interfascicular tissue; both epineurium and perineurium are thin and slender. The
      principal arteries are placed between funiculus and epineurium. Either epineurial
      or interfascicular neurorrhaphy could be produced and mono- or polyfascicular
      nerve grafts can be used. In both temporofacial and cervicofacial primary
      branches, the fascicular distribution was from four to five fascicles in 64% of
      cases with abundant connective interfascicular tissue involving the principal
      arteries. The interfascicular surgical technique is of election, but the
      epineurial suture must not be discarded. Nerve graft must be polyfascicular. The
      goal of nerve repair is to obtain the restoration of anatomic continuity of the
      most of axons by means of a complete fascicular alignment, in which detailed
      knowledge of the intraneural topography of the facial nerve must be required for
      reliable microsurgical reparation.

PMID- 17538322
TI  - The pterygopalatine fossa: an anatomic report.
AB  - The pterygopalatine fossa (PPF) is a small anatomic region of particular interest
      in cranial base surgery. Infectious diseases and malignancy may spread through
      the PPF to contiguous areas as a result of the low resistance offered by the
      numerous foramina and fissures that surrounds the fossa. We present an anatomic
      report on the PPF. Twelve sides of six fixed cadaveric heads were dissected
      through a LeFort I maxillary osteotomy with transantral exposure of the
      neurovascular content of the PPF. Arterial vascular patterns of the maxillary
      artery were observed. The pterygopalatine fossa is a deeply located small
      anatomic region with a rich neurovascular content. The third portion of the
      maxillary artery in the PPF may demonstrate a variable vascular morphology. A
      correct understanding and knowledge of the anatomic structures lodged into the
      PPF, as well as their relationships and functions, remain crucial to minimizing
      postsurgical morbidity and intraoperative complications.

PMID- 17538323
TI  - Immunohistochemical study of differences between the muscle fiber types in the
      pars peripheralis and marginalis.
AB  - The aim of this study was to evaluate the immunohistochemical differences between
      the muscular fiber types in the pars peripheralis and pars marginalis of human
      orbicularis oris muscle. Five upper lips of fresh human adult cadavers were used.
      Full thickness of the upper lip, 5 mm in width, was harvested vertically at a
      peak point of cupid's bow. Troponin I-SS and Troponin I-FS antibodies were used
      to determinate the slow and fast skeletal muscle fibers. The pars peripheralis is
      composed of slow fibers (22%) and fast fibers (73%). The pars marginalis is
      composed of slow fibers (30%) and fast fibers (66%). We assume that the pars
      peripheralis and pars marginalis should be repaired sortably because the muscle
      reaction and endurance are not the same.

PMID- 17538324
TI  - Split rib cranioplasty for aplasia cutis congenita and traumatic skull defects:
      more than 30 years of follow-up.
AB  - Aplasia cutis is a rare skin defect usually presenting over the vertex of the
      skull. An underlying bone defect is found in approximately 20% of patients. Most
      skull defects close spontaneously. However, when there are no signs of
      ossification, closure is mandatory. We present our experience in three patients.
      Our first patient had an aplasia cutis with a skull defect. The split rib graft
      procedure was used without complications, and a good cosmetic and functional
      result was achieved. The second patient was operated on for cerebral bleeding
      after an arteriovenous aneurysm, and a bony defect could not be closed after that
      procedure. At a later stage, the defect was filled with split rib grafts, and
      sufficient protection was achieved and documented after more than 30 years. The
      third patient was born with an aplasia cutis congenita with a skull defect. The
      bony defect was filled with split rib grafts without complications at an age of 5
      years. Follow-up shows a functional result with a firm skull. Patients with
      aplasia cutis may have skull defects that will not close by themselves. We
      present three patients with a bony defect who were reconstructed with split rib
      grafts. After a long period of follow-up, there remains good cosmetic and
      functional results. Defects of the skull in children can be reconstructed with
      split rib grafts that will accommodate the growing skeleton and give good
      protection of the brain from an early age on.

PMID- 17538325
TI  - Reconstruction of traumatic orbital floor fractures with resorbable mesh plate.
AB  - Various materials such as autogenous bone, cartilage and alloplastic implants
      have been used to reconstruct orbital floor fractures. A new material is needed
      because of disadvantages of nonresorbable alloplastic materials and difficulties
      in harvesting autogenous tissues. In this study safety and value of the use of
      resorbable mesh plate in the treatment of orbital floor fractures are discussed.
      Between 2002 and 2004 a total of 17 maxillofacial trauma patients complicated
      with orbital floor fractures were treated with resorbable mesh plate through
      subciliary or transconjunctival incisions. Pure blow-out fractures were
      determined in 6 patients and 11 patients had accompanying maxillofacial
      fractures. Resorbable plate was easily shaped to fit to the orbital floor by
      cutting with scissors. Patients were evaluated clinically and with computed
      tomography scans preoperatively and at 3-, 6- and 12-month intervals
      postoperatively. Twelve patients had preoperative enophthalmos. Two patients had
      diplopia that was corrected postoperatively. In all 17 cases there was no
      evidence of infection, diplopia and gaze restriction postoperatively. Scleral
      show appeared in three patients by the second postoperative week but resolved
      totally within 3 to 6 weeks except one patient. In this patient anterior
      displacement of mesh was evident which caused ectropion and enophthalmos and
      required re-operation. No any other mesh related problems were seen at 15 months
      mean follow-up time. The advantage of the resorbable mesh system in orbital floor
      fracture is the maintenance of orbital contents against herniation forces during
      the initial phase of healing and then complete resorption through natural
      processes after its support is no longer needed. Our experience represents that
      resorbable mesh is a safe and effective material for reconstruction of the
      selected, non-extensive orbital floor fractures.

PMID- 17538326
TI  - Multiple and comminuted mandibular fractures: treatment outlines in adverse
      medical conditions in Iraq.
AB  - This study was conducted to evaluate prospectively the simple and more reliable
      methods in the treatment of multiple and comminuted mandibular fractures in
      hospitals with limited facilities and a high influx rate of trauma patients such
      as ours in Baghdad. One hundred patients with multiple and comminuted mandibular
      fractures of different severities were included in this study. Fifty-four
      patients were with comminuted and 46 were with multiple mandibular fractures.
      Eighty-eight patients had isolated mandibular fractures, and 12 had other
      associated facial bones fractures. Seventy-two patients were treated solely with
      maxillomandibular fixation. Thirteen patients were treated with different methods
      of internal fixation; the remainder was treated conservatively, functionally, or
      with different combinations of closed and open reduction methods. There was a
      statistically significant difference (P < 0.05) for fractures healing in relation
      to the type, severity, and etiology of the fracture. Eighty-four patients had
      fractures healed to bony union, 4 ended with nonunited fractures, and 10 patients
      had bone loss. Four patients developed infection, thus the infection rate was 4%
      for all, and 2.17% and 5.56% for patients with multiple and comminuted fractures,
      respectively. Seventeen patients required further surgeries for facial
      recontouring. The results of this study underscore the efficacy of closed
      reduction for treating multiple and comminuted mandibular fractures in terms of
      its simplicity, the availability of materials and instruments, and the favorable
      outcomes.

PMID- 17538327
TI  - Transcervical submandibular sialoadenectomy.
AB  - The submandibular glands are subject to several pathologies that require
      excision. The most common problem that affects these salivary glands is
      sialadenitis combined with sialolithiasis. This problem occurs in the
      submandibular gland 10 times more frequently than it does in the parotid gland.
      Other illnesses frequently involving the submandibular glands are represented by
      sialadenosis and benign, malign, and intermediate neoplasms. Diagnosis of any
      disturbance in the submandibular gland involves both a clinical and instrumental
      (echography, traditional radiography [ortopantomography] and eventually computed
      tomography (CT) or magnetic resonance imaging) assessment. Surgery is the usual
      method of treatment of both chronic sialadenitis and neoplasms in the
      submandibular gland. A submandibular gland surgical approach can be cervical,
      intraoral, or endoscopic. The authors present their clinical experience with a
      total of 40 patients with illnesses involving the submandibular gland treated
      with submandibular gland excision by a transcervical approach. Their experience
      suggests that this approach entails a relatively simple procedure, involves low
      risks for the nerve structure around the gland, permits wide resection margins
      for neoplasms, and incurs little aesthetic damage.

PMID- 17538328
TI  - Anterior skull base reconstruction with a galeal-pericranial flap.
AB  - Excision of neoplasm and trauma involving the anterior cranial base may often
      result in communication between the intracranial and extracranial compartments.
      Many techniques have been proposed to obtain a watertight separation. We report
      our 5 years of experience in the management of anterior skull base defects using
      a galeal-pericranial flap. Between January 2001 and April 2006, 22 patients were
      treated for a cranial base reconstruction at the University of Messina. Five of
      them presented with persistent cerebrospinal fluid (CSF) leak after previous
      craniofacial trauma. Ten underwent a combined maxillofacial-neurosurgical
      approach for the removal of a benign tumor involving the anterior skull base.
      Seven had severe craniofacial trauma, which required an intervention of
      reconstruction of the anterior skull base. In the whole series, a galeal
      pericranial flap was used to separate intra- and extracranial compartments. No
      patients developed postoperative brain contusions or subdural-epidural blood
      collections. Throughout the follow-up period, there was no evidence of flap
      failure. In all but one patient, no postoperative CSF leak was evident. In one
      patient, a mild transient postoperative CSF leakage was present. There has been
      no recurrent CSF leak or meningitis. The follow up average of 23 months shows no
      incidence of infection. Even if our series does not comprise malignancies and
      previously irradiated patients, our data confirm the validity of the galeal-
      pericranial flap for the surgical management of minimal and moderately sized
      defects of anterior cranial base.

PMID- 17538329
TI  - Bicortical biodegradable screws for rigid fixation of traumatic sagittal split
      mandibular fracture.
AB  - Rigid fixation is the most important issue in the bone healing process. Although
      internal metallic bone fixation has become increasingly popular over the past 10
      years, the presence of several potential problems of metallic bone implants with
      the popularity of the use of biodegradable plates and screws for
      craniomaxillofacial fixation have increased in the last 10 years. Rigid fixation
      of bony fragments was achieved by bicortical applied biodegradable screws in a
      patient with a sagittal oblique mandibular fracture. Precise bone reduction was
      maintained with bicortical applied biodegradable screws in the postoperative
      period. The postoperative period was uneventful and the patient retained the
      intraoperatively achieved perfect occlusion within a 9-month follow-up period. In
      this particular case, the advantages of use of resorbable fixation systems are
      combined with the advantages of bicortical screw fixation of split osteotomy
      without sacrificing the stability of rigid fixation.

PMID- 17538330
TI  - Bone reconstruction of the maxillary alveolus for subsequent insertion of a
      dental implant in patients with cleft lip and palate.
AB  - Bone grafting of maxillary alveolus cleft defect followed by insertion of dental
      implant may be a good alternative to conventional prosthetic treatment. The
      principle is the formation of stable alveolar crest with a sufficient three
      dimensional volume. The problems are lack and quality of mucoperiosteum for the
      reconstruction of shell and bone gap characteristics for bone graft intake. The
      procedure was carried out by a single surgeon (MD) in 45 patients between 29
      August 2001 and 30 June 2006, with an 86.7% success rate. The success was defined
      as completed process with dental implant insertion and its loading by a
      prosthetic suprastructure without a failure for at least 15 months from that last
      step. The success rate mainly depends on 1) good alveolar arch flow of maxilla
      segments in both horizontal and vertical planes; 2) the height of osseous poles
      of at least 12 mm and onlay augmentation of built-up section does not work; 3)
      adequate volume of cancellous bone graft, 3.7 cm on average. On the basis of
      histologic verification and clinical findings, the bone graft is matured enough
      to ensure a primary stability of a fixture in 12.5 weeks after reconstruction.
      Early load may prevent bone resorption. Prediction of complications are as
      follows: 1) graft resorption increases according to gap size and low possibility
      of revascularization; 2) a higher number of complications are linked to presence
      of oronasal fistula and to scarring of soft tissues; 3) because of more gracile
      skeleton and female metabolism, the risk is higher in women.

PMID- 17538331
TI  - Combination of costal cartilage graft and rib-latissimus dorsi flap: a new
      strategy for secondary reconstruction of the maxilla.
AB  - In secondary reconstruction of the maxilla, skeletal reconstruction as well as
      soft tissue augmentation is required to obtain a good contour. We present a new
      strategy for combining a costal cartilage graft with a rib-latissimus dorsi flap.
      We used this method to treat a 39-year-old man who had previously undergone total
      maxillectomy. First, a vascularized rib, elevated together with a latissimus
      dorsi flap, was fixed between the middle of the maxilla and the edge of the
      zygomatic arch. The small defects that could not be reconstructed with the rib
      only were reconstructed with a costal cartilage graft. The patient did not
      develop any postoperative infection or flap necrosis. Thirteen months after the
      secondary reconstruction, he presented with a good contour of the cheek. Our
      method was effective for the reconstruction of a complex skeletal defect of the
      maxilla.

PMID- 17538332
TI  - Easy facial analysis using the facial golden mask.
AB  - For over 2000 years, many artists and scientists have tried to understand or
      quantify the form of the perfect, ideal, or most beautiful face both in art and
      in vivo (life). A mathematical relationship has been consistently and repeatedly
      reported to be present in beautiful things. This particular relationship is the
      golden ratio. It is a mathematical ratio of 1.618:1 that seems to appear
      recurrently in beautiful things in nature as well as in other things that are
      seen as beautiful. Dr. Marquardt made the facial golden mask that contains and
      includes all of the one-dimensional and two-dimensional geometric golden elements
      formed from the golden ratio. The purpose of this study is to evaluate the
      usefulness of the golden facial mask. In 40 cases, the authors applied the facial
      golden mask to preoperative and postoperative photographs and scored each
      photograph on a 1 to 5 scale from the perspective of their personal aesthetic
      views. The score was lower when the facial deformity was severe, whereas it was
      higher when the face was attractive. Compared with the average scores of facial
      mask applied photographs and nonapplied photographs using a nonparametric test,
      statistical significance was not reached (P > 0.05). This implies that the facial
      golden mask may be used as an analytical tool. The facial golden mask is easy to
      apply, inexpensive, and relatively objective. Therefore, the authors introduce it
      as a useful facial analysis.

PMID- 17538333
TI  - Subtotal scalp reconstruction after traumatic avulsion: a technical note.
AB  - We present the case of a 19-year-old female who suffered traumatic avulsion of
      the entire scalp while working with textile industrial machinery and present a
      pertinent review of the anatomy of the scalp.

PMID- 17538334
TI  - Computer-aided surgical treatment of bilateral choanal atresia.
AB  - Transnasal surgical treatment of congenital choanal atresia is difficult. A
      limited view to the surgical field often accounts for poor results. An occurrence
      of a restenosis is frequently observed requiring difficult revision surgery.
      Severe complications include bleeding, skull base and intracranial injuries as
      well as orbital injuries. We describe the use of an optical computed tomography
      data-based navigation system for surgical planning and intraoperative guidance to
      improve treatment outcome. Computer-assisted planning and computed tomography
      data-based navigation was used in the case of a 2-year-old infant with a history
      of Treacher Collins syndrome associated with bilateral choanal atresia. To reduce
      target registration error, registration markers were fixed to a maxillary dental
      splint that was inserted intraorally during image data acquisition and patient
      registration. A combined technique using navigational guidance and nasal and
      retropalatal endoscopy was used for instrument navigation successfully removing
      the bony atretic plates. This clinical report demonstrates the feasibility of a
      combined approach with surgical navigation. A larger clinical series with long
      term follow up will be needed to determine the reproducibility and validation of
      potential benefits.

PMID- 17538335
TI  - A new approach to alar rim defects: mucocartilaginous turnover flap.
AB  - The main principle of reconstructive surgery is replacement of the defective
      tissues with like tissues. A full-thickness defect of the nasal ala should be
      reconstructed in three layers: innermost mucosal layer, outermost skin, and the
      cartilage in-between. The aim of this study is to describe a technique for single
      stage, three-layer reconstruction of the full-thickness ala nasi defects. This
      technique was used on three patients with tumors involving the nasal ala.
      Resulting full-thickness defects are reconstructed with a mucocartilaginous
      turnover flap planned from the contralateral side. Aesthetically acceptable
      results are obtained without the compromise of the nasal airway and with minimal
      donor site morbidity. None of the patients requested a revision operation. In
      conclusion, this is a novel technique with minimal donor site morbidity and good
      postoperative results. Moreover, lost tissues are replaced with exactly the same
      kind of tissues.

PMID- 17538336
TI  - Late reconstruction of the complex orbital fractures with computer-aided design
      and computer-aided manufacturing technique.
AB  - BACKGROUND: To construct three-dimensional (3D) imaging and computer generated
      models of complex orbital fractures, and develop a Computer-Aided Design/Computer
      Aided Manufacture (CAD/CAM) system to help improve the surgical planning of
      complex orbital fracture and promote its outcome. METHODS: A prospective study
      was carried out on 17 patients with unilateral complex orbital fractures from Mar
      2003 to Mar 2006 at the Shanghai ninth people's hospital. The utilization of a
      CAD/CAM technique based on Helical computer tomography data, with
      stereolithographical (SLA) modelling as intermediate step, enabled surgeons to
      plan for the surgical progress of osteotomy, movement, reposition, fixation and
      material implanting. Orbital volume was calculated pre and post-operatively.
      Orbital fracture reconstruction and globe repositioning was performed and
      followed up 3-9 months post-treatment. Ocular function and aesthetic deformities
      such as enophthalmos, diplopia and extraocular motility problems were accessed.
      The data was processed with SAS 6.17 statistical software. RESULTS: 17 patients
      with complex orbital fractures underwent successful orbital fracture
      reconstruction surgery. The deformities of orbit, medial canthus, nose, zygomata,
      maxillary and frontal bone were well corrected. The volume of reconstructed orbit
      was approximately symmetrical with respect to the contralateral orbit.
      Enophthalmos was corrected and diplopia, extraocular movement were improved.
      CONCLUSIONS: CAD/CAM system enables the surgeon to predict reconstructive
      surgical steps before the operation, and can help to improve the outcome of
      surgery. This technique may be proved as one of the most useful clinical tools
      for orbital surgery.

PMID- 17538337
TI  - Iatrogenic traumatic brain injury: penetration of Kirschner's knitting needle
      into the middle cranial cavity.
AB  - Traumatic penetrations of foreign objects into the craniocerebral cavity are
      often encountered in the department of emergency and traumatology. A 5-year-old
      child was brought to the department of pediatric neurosurgery with a severe
      headache and fatigue. On admission, the patient had initial neurologic
      examinations and radiologic scans. The consciousness assessment by Glasgow Coma
      Scale was 13. Neuroradiologic studies revealed a long hyperdense object extending
      from the extracranial cavity into the middle cranial fossa. A thorough history
      was obtained with attention to how and when the injury was sustained. Two weeks
      before the incident, the child had a blunt trauma of mandibular fractures with
      dislocation of the temporomandibular joint. Maxillomandibular surgery was
      performed with a Kirschner's knitting needle to fixate the temporomandibular
      articulation and simple interdental ligatures for mandibular fracture
      stabilization. The present radiologic film suggested that the mandibular fracture
      was not properly fixated allowing the mobilization of Kirschner's needle moving
      either externally or internally. A standard pterional access with
      frontotemporosphenoidal approach was performed according to the method of
      Yasargil and Oikawa-Miyazawa followed by an extradural approach method of Dolenc
      to the middle cranial structure at the skull base. Several stages of hemostasis
      were carried out with electrohemocoagulation on the penetrated Kirschner's needle
      during the needle extracting process at the extradural space of the middle
      cranial fossa. Two weeks postoperatively, computed tomography scan revealed the
      supratentorial and middle craniocerebral structures were in symmetric
      localization. The patient was free of neurologic deficits with no signs of
      excessive cerebrospinal fluid volume formation. In conclusion, the method of
      fixation requires appropriate application techniques to ensure adequate fracture
      fixation during the healing cascade. The neurosurgical approach also requires a
      specific measure on its management and rehabilitation for the maintenance of such
      a patient.

PMID- 17538338
TI  - Simultaneous obliteration and treatment of infected frontal sinus fractures:
      novel use of the fibula flap.
AB  - We present two cases of infected frontal sinus fractures requiring simultaneous
      obliteration of the frontal sinus and reconstruction of the horizontal buttress.
      In both cases, a free fibula flap was used for obliteration and bony
      reconstruction in a single stage. We believe that this is a novel technique for
      treatment of infected frontal sinus fractures obviating the need for secondary
      staged procedures.

PMID- 17538339
TI  - Hard palate mucoperiosteal graft for posterior lamellar reconstruction of the
      upper eyelid: histologic rationale.
AB  - Reconstruction of full-thickness upper eyelid defects often requires repair of
      both the anterior lamella (skin and orbicularis oculis muscle) and the posterior
      lamella (tarsus and conjunctiva). Various autogenous grafts have been used for
      posterior lamellar reconstruction, but it is still unclear which material is most
      suitable for repairing the posterior lamella. We report a patient in whom a
      subtotal defect of upper eyelid was reconstructed with a bipedicled myocutaneous
      flap lined by hard palate mucoperiosteum. We also examined tarsoconjunctiva,
      labial mucosa, hard palate mucoperiosteum, and auricular cartilage histologically
      and assessed the histologic features of these tissues as substitutes for the
      posterior lamella. An even and stable upper eyelid was formed by our method of
      reconstruction. A mucoperiosteal graft from the hard palate bears a close
      resemblance to the tarsoconjunctiva histologically because it contains both
      fibrous connective tissue and a mucous membrane. The graft took completely and
      there was no donor site morbidity or postoperative complications. A hard palate
      mucoperiosteal graft may be an optimal substitute for the posterior lamella of
      the upper eyelid.

PMID- 17538340
TI  - Commissuroplasty for macrostomia.
AB  - Macrostomia is a rare facial malformation caused by failure of mesodermal
      migration merging to obliterate the embryonic grooves between the maxillary and
      mandibular processes during the early phase of gestation. This kind of
      malformation may require the use of several surgical techniques to repair the
      facial structure. Bibliographic studies concerning the repair of this
      malformation are focused on the description of mucosa, muscle, and skin flaps
      disconnected between them. This article presents a description of a unique
      myomucosal flap from vermillion for the correction of the existing malformation
      in the oral commissure.

PMID- 17538341
TI  - Frontal bone fractures: new technique of closed reduction.
AB  - Fractures of the nasofrontal orbital complex account for 5% of all facial
      fractures. Mean hospitalization is usually longer than for other types of facial
      lesions, independent of the trauma responsible (road accidents, sport, falls,
      firearm wounds, and so on). The choice of treatment, usually dictated by the site
      and extent of the damage, is important because inadequate treatment may lead to
      immediate or subsequent complications. A conservative surgical technique for use
      in the treatment of non-comminuted frontal lesions is described, which consists
      of the closed reduction of the depressed fragments by means of a small
      percutaneous approach. Before surgery, a computed tomography scan is carried out
      with 2-mm slices both in the axial and coronal projections, mandatory to evaluate
      the orbital roof and frontal region. The peripheral limits of the frontal region
      fracture are marked on the skin, a punctiform incision made in the area of
      maximum depression, and a calibrated drill inserted. Two small holes are created
      in the center of the depressed fragment and two pins screwed in, both of a length
      to allow the surgeon an easy reduction maneuver. A radiographic evaluation is
      then performed to check the correct alignment of the previously depressed
      fragment, the two percutaneous pins removed, and two sutures applied, if
      necessary. This technique avoids the scarring often observed after the open
      reduction technique and, in selected cases, treatment may be carried out in
      neuroleptanalgesia reducing operating as well as hospitalization times and
      healthcare costs.

PMID- 17538342
TI  - Repeated tissue expansions on split-thickness skin graft in a patient with
      neurocutaneous syndrome.
AB  - Soft tissue expansion is a mechanical process that increases the surface area of
      local tissue available for reconstructive procedures. In most cases, adjacent
      tissue that matches the recipient site in color, texture, and hair-bearing
      quality is preferred for tissue expansion. In this particular case with
      neurocutaneous syndrome, the defects that resulted from removal of parts of a
      giant hairy nevus overlying the latissimus dorsi muscle bilaterally were grafted
      with a split-thickness skin graft. Two expanders were then placed under the
      latissimus dorsi muscles. After full expansion of the grafted area, some part of
      the remaining nevus surrounding the grafted area was removed and the defects were
      covered with the expanded skin graft obtained after deflation of the expanders.
      The expanders placed under the latissimus dorsi muscle in the first operation
      were reused in the second operation to obtain a second expansion of the skin
      graft. After the second expansion of the skin graft, the expanders were deflated
      and another portion of the remaining nevus surrounding the grafted area was
      removed. The resulting defects were again covered with the excess expanded skin
      graft. Although repeated expansion of the skin graft is a time-consuming and
      laborious process, it eliminates the need for taking repeated skin grafts; it
      decreases skin graft donor site morbidity; it decreases possible infectious
      complications of tissue expansion by decreasing the number of surgical
      interventions to the expander pocket; and it increases the aesthetic outcome by
      keeping all the surgical scars around the grafted area without extending them
      into healthy surrounding skin.

PMID- 17538343
TI  - A paramedian cleft of the lower lip.
AB  - We report the unusual case of a baby with a paramedian cleft of the lower lip. In
      1976, Tessier described a classification of craniofacial clefts based on personal
      observations, and he predicted the possibility of further clefts being discovered
      by labeling midline mandibular clefts "30." This case of a paramedian cleft of
      the lower lip would fit into what could be a new Tessier 28/29 cleft. In the
      future, clefts in new locations around the mouth may be seen, thus filling the
      gaps in Tessier's classification.

PMID- 17538344
TI  - Progressive maxillary sinus hypoplasia with open ostium.
AB  - Maxillary sinus hypoplasia (MSH) is an uncommon clinical entity that represents a
      persistent decrease in sinus volume resulting from a centripetal retraction of
      the maxillary sinus walls. Pathophysiology of MSH is still controversial.
      Obstruction of the maxillary sinus ostium and negative pressure in the sinus has
      been mostly implicated in the development of MSH in most of the reported cases.
      We present a case of progressive unilateral MSH, which has an open ethmoid
      infundibulum and also presence of an open accessory ostium on the same side.
      Based on these findings, we propose that ventilatory dysfunction resulting from
      ostial obstruction alone cannot be accepted as the primary and sole etiologic
      factor in the pathogenesis of MSH.

PMID- 17538345
TI  - Leishmania scar: a risk factor for the development of basal cell carcinomas.
AB  - Basal cell carcinoma is a malignant epithelial neoplasm of skin that usually
      arises in areas of chronic sun exposure. It rarely originates from smallpox
      vaccination scars, chickenpox scars, previous surgical scars, or burn scars. We
      present a case of basal cell carcinoma arising on a leishmania scar on the nasal
      dorsum 30 years after the primary lesion.

PMID- 17538348
TI  - One-stage surgical management for multilevel tuberculous spondylitis of the upper
      thoracic region by anterior decompression, strut autografting, posterior
      instrumentation, and fusion.
AB  - STUDY DESIGN: A retrospective clinical study of 1-stage surgical management for
      multilevel tuberculous spondylitis of the upper thoracic region (MTSUTR).
      OBJECTIVE: MTSUTR has rarely been documented in the literature. We present a
      retrospective clinical study of 23 patients with MTSUTR treated by anterior
      decompression, strut autografting, posterior instrumentation, and fusion. The
      purpose was to determine the clinical efficacy of such surgical treatment for
      MTSUTR. SUMMARY OF BACKGROUND DATA: It is considered safe and effective to treat
      surgically tuberculous spondylitis with local spinal cord compression. Many
      reports have documented a good clinical efficacy of surgical management for
      spinal tuberculosis. However, how to deal with MTSUTR is rarely reported in the
      literature. METHODS: There were 14 men and 9 women, with average age of 35 years.
      All patients underwent 1 stage anterior debridement, strut autografting, and
      posterior instrumentation and received combined medication antituberculosis
      chemotherapy for 12 to 24 months (average 18 mo). The following data were
      followed up for an average period of 42 months (24 to 60 mo) in these patients:
      deformity angle, neurologic function, and spinal bony fusion. RESULTS: The
      average preoperative deformity angle was 44 degrees, correcting to 20-degree
      postoperatively and 24 degrees at final follow up. In the series, 19 patients
      with preoperative neurologic deficit restored by 1.3 grades according to Frankel.
      All patients got bony spinal fusion within 6 months postoperatively. There was no
      recurrent tuberculous infection. CONCLUSIONS: Single-stage anterior debridement,
      strut autografting, posterior instrumentation, and fusion proved safe and
      effective for MTSUTR, which can achieve goals of complete spinal cord
      decompression and good deformity correction.

PMID- 17538349
TI  - Timing of paired points and surface matching registration in three-dimensional
      (3D) image-guided spinal surgery.
AB  - Image-guidance can increase the safety and accuracy of spinal instrumentation
      placement. However, many spine surgeons are reluctant to incorporate spinal image
      guidance into their surgical practice due to the perception that it is time
      consuming and tedious, especially the task of vertebral registration. The authors
      evaluated the time required for paired points and surface matching registration
      when using the BrainLAB (BrainLAB, Westchester, IL) image-guided spine
      application for spinal surgery cases. The time required to register vertebral
      segments using paired points and surface matching techniques was assessed in 13
      consecutive patients undergoing spinal fusions by the senior author. Overall, 23
      vertebral segments were registered spanning from T1 to S1. Note was made of the
      vertebral segments that required reregistration due to poor accuracy. The average
      time required to register a single vertebral segment using the paired points and
      surface matching technique was 117 seconds (1 min 57 s). Average accuracy
      obtained was 0.9 mm. Inaccurate registration occurred in 3/23 (13%) of the
      segments requiring a second attempt at registration. In 3/23 (13%) of segments,
      adequate navigation accuracy was maintained on an adjacent vertebral segment
      thereby allowing for instrumentation to be placed in that adjacent segment
      without having to register that segment. Though associated with a learning curve,
      image-guidance can be used effectively and efficiently in spinal surgery. Average
      time required for registration of a vertebral segment using the BrainLAB spine
      application in this study was less than 2 minutes. The average accuracy obtained
      was 0.9 mm.

PMID- 17538350
TI  - Safety and efficacy of implant removal for patients with recurrent back pain
      after a failed degenerative lumbar spine surgery.
AB  - The etiology of failed degenerative lumbar spine surgery may include a wide array
      of conditions. There is a group of patients who have recurrence of back pain
      despite a solid fusion in the absence of any obvious pain generator. Implant
      removal in those patients is a controversial optional treatment. The purpose of
      this study was to evaluate the efficacy and safety of implant removal and to
      determine the possible predictors of its efficacy. Twenty-five patients (10 M, 15
      F) with an average age of 44 (18 to 74) were retrospectively evaluated. All
      patients had prior titanium posterior pedicle screw instrumentation and fusion
      for lumbar degenerative disorders. Twenty patients with increase in pain during
      palpation of the operative side underwent a preoperative anesthetic injection at
      the site of their trigger points. Patients' clinical charts, operative notes, and
      preoperative x-rays were evaluated. Relief of pain was evaluated by the percent
      Visual Analog Scale (VAS) pain change due to implant removal. Functional
      improvement was rated on a five-point scale. Predictors of pain relief were
      analyzed by using bivariate analysis. A P value <0.05 was considered significant.
      Average follow-up period was 20 (12 to 37) months. The median time after the
      index operation and the recurrence of pain was 13.5 (1 to 119) months. VAS
      decrease after implant removal was 50% (P<0.001). Functional improvement was
      reported by 84% of patients. One patient developed a superficial infection
      managed successfully. Bivariate analysis showed that percent VAS change after
      injection, months free of pain after the index operation, and provocation of pain
      by palpation were significant predictors for pain relief (P<0.05). Removal of the
      implant may be an efficient and safe procedure for carefully selected patients
      and the most consistent predictor of its efficacy is the percent pain relief
      after the diagnostic injection of the painful operative side.

PMID- 17538351
TI  - Circumferential arthrodesis using PEEK cages at the lumbar spine.
AB  - Usual interbody cages at the lumbar spine are made of titanium or carbon fiber
      polyetheretherketone (PEEK). Pure PEEK cages have more recently been proposed for
      its lower elasticity modulus. The goal of our study was to investigate a series
      of patients with circumferential fixation using anterior PEEK cages for
      degenerative lumbar spine disorders with a specific interest in the local
      lordosis. Fifty-seven consecutive patients aged 54.6 years (29 to 75) were
      reviewed. The level of arthrodesis varied from L2L3 to L5S1. The clinical status
      and the radiologic variations in local lordosis at the level of arthrodesis were
      measured. Decrease in lordosis at follow-up was tested in a multivariate analysis
      regarding age, obesity, spinal level, bone graft amount, type of posterior
      instrumentation, postoperative lordosis increase, and cage height. The average
      follow-up was 5.7 years (4 to 8). Clinical outcomes were excellent or good in 49
      cases. Fusion was definite in 56 cases. Although 47 patients had no change in
      lordosis after surgery, 10 cases showed lordosis increase (8.2 degrees; 5 to 12).
      At follow-up, local lordosis decreased in 13 cases (5.6 degrees; 4 to 8). The
      linear model was significant (P<0.001; R=0.590) showing that loss in lordosis was
      related with postoperative lordosis increase (P=0.01), cage height (P<0.001),
      posterior instrumentation rigidity (P=0.026), age (P=0.047), and low level
      (P=0.013). Lumbar circumferential arthrodesis using PEEK cages provided good
      clinical results and fusion rate. However, lordosis correction was not maintained
      at follow-up, especially at lower levels, using high cages, in older patients,
      and when associated with a rigid primary posterior instrumentation. Regarding the
      last point, this is likely that the order of the instrumentation (posterior
      first, then anterior) played a role in the loss of lordosis in case of rigid
      posterior fixation.

PMID- 17538352
TI  - Questionnaire study of neuromonitoring availability and usage for spine surgery.
AB  - STUDY DESIGN: Questionnaire study presented to practicing spine surgeons.
      OBJECTIVE: To evaluate surgeon preference and availability of selected
      electrophysiologic neuromonitoring for different spine surgeries. SUMMARY OF
      BACKGROUND DATA: Maximizing the safety of spinal procedures and limiting
      potential iatrogenic neurologic injury has made intraoperative neuromonitoring an
      attractive option. METHODS: We distributed a questionnaire to 180 orthopedic
      spine surgeons and neurosurgeons at a clinically oriented spine meeting asking
      surgeon preference and availability of various types of intraoperative
      neuromonitoring modalities for different types of surgical procedures.
      Demographic data were also gathered. RESULTS: Somatosensory evoked potentials
      (SSEPs) were the most available neuromonitoring modality, followed by
      electromyographies and motor-evoked potentials. In both anterior and posterior
      cervical surgery, SSEPs were the most preferred modality. MEPs were frequently
      preferred in myelopathic cervical cases. Almost 70% preferred some
      neuromonitoring for anterior thoracic/thoracolumbar cases and 55% for posterior
      thoracic/thoracolumbar cases. Surgeon satisfaction was related to the number of
      available neuromonitoring modalities. No significant differences were found
      between orthopedist and neurosurgeon preferences. Fellowship-trained surgeons
      were more likely to use neuromonitoring for specific indications. CONCLUSIONS:
      SSEPs remains the most widely available and preferred type of neuromonitoring for
      spine surgeons. The type of case and neurologic status of patient (eg, presence
      of myelopathy) affects these choices. Surgeons were more satisfied with greater
      neuromonitoring availability, and were more likely to use neuromonitoring if they
      had a fellowship background.

PMID- 17538353
TI  - Septic arthritis of lumbar facet joints without predisposing infection.
AB  - Septic arthritis of a lumbar facet joint is a rare clinical entity and most
      articles have reported a single case. There have been few studies that have
      evaluated the clinical and imaging features of septic arthritis of lumbar facet
      joints. The clinical data of 5 patients diagnosed with septic arthritis of lumbar
      facet joints were retrospectively studied. The average age of 5 patients was 73.6
      years. All patients had elevated temperature at admission (37.7 degrees C).
      Leukocyte count was tested in all 5 patients and was elevated in only 2 patients.
      Erythrocyte sedimentation rate and C-reactive protein were examined and were
      elevated in all 5 cases. Magnetic resonance imaging was accurate in identifying
      the septic joint and associated abscess formation. All patients were treated with
      bed rest and received intravenous antibiotics for an average of 33.3 days. Four
      of 5 patients had positive outcomes with full recoveries and no evidence of
      recurrent infections. One patient exhibited evidence of recurrent infection and
      required open facet arthrotomy and paraspinal muscle debridement after
      intravenous administration of antibiotics. Septic arthritis of the lumbar facet
      joint is a rare cause of low back pain. It is important to ascertain the
      diagnosis at the earliest possible stage and to start intravenous antibiotics
      therapy as soon as possible. Magnetic resonance imaging is quite a sensitive
      modality for identifying infection of the lumbar facet joint. Familiarity with
      its clinical symptoms and radiographic features is necessary to avoid
      misdiagnosis of this condition.

PMID- 17538354
TI  - Cervical hemilaminoplasty: technical note.
AB  - Ten patients with cervical spinal schwannomas were operated using a new posterior
      approach, termed cervical hemilaminoplasty. A thread wire saw (T-saw) was used to
      cut the lamina at the center of the spinous process and at the unilateral pars
      interarticularis on the affected side. The unilateral lamina, the inferior
      articular process, and half of the spinous process were resected as a single
      mass. After tumor excision, the resected lamina was restored to the original site
      and fixed. Fusion technique was not required. The mean number of resected and
      restored lamina was 1.5. No instability of the cervical spine was detected using
      flexion/extension x-ray photography. Although worsening of radicular motor
      function was observed in 2 cases, the weakness was not permanent and both cases
      showed full recovery. Postoperative magnetic resonance imaging was performed in 7
      of the 10 cases and showed no recurrences. Cervical hemilaminoplasty is a useful
      posterior approach method for spinal tumors and especially dumbbell-type tumors.
      This method provides wide exposure of the foramen and of the inside of the canal.
      Furthermore, it allows reconstruction of the posterior element of the spinal
      canal and results in good stability.

PMID- 17538355
TI  - Spinal surgery and ophthalmic complications: a French survey with review of 17
      cases.
AB  - OBJECTIVES: Ocular complications after spine surgery are incompletely understood
      and are not as rare as implied by recent publications. In 13 out of 15 published
      case reports, ocular complications are attributed mainly to compression. But in
      66 cases reported in 4 series in the literature, compression seems to play a role
      in less than 10 cases. However, 3 out of the 4 series lack sufficient detail to
      support this mechanism clearly. Our objectives were to identify the mechanisms
      and specific risk factors associated with this devastating complication, to help
      in prevention. METHODS: A 2-page survey was sent to all French orthopedic centers
      specializing in spine surgery (28 centers) requesting information regarding any
      patients who had experienced visual deficits after spine surgery. Respondents
      were asked to identify presence of commonly cited preoperative risk factors,
      including ophthalmologic diagnosis and local signs (eyelid or conjunctival edema,
      periorbital numbness, or paresthesia) and intraoperative risks, such as
      positioning of the head, to clarify the possible mechanisms. Seventeen patients
      were thus included. RESULTS: Two main mechanisms were identified. First, ocular
      compression (9 cases) characterized by a unilateral definitive blindness with
      local signs due to a central retinal artery occlusion. Second, internal carotid
      thromboembolism (4 cases) associated with head rotation toward the ipsilateral
      side, causing an ischemic optic neuropathy with a unilateral partial and
      potentially regressive visual loss. CONCLUSIONS: The authors propose 2 preventive
      measures: modification of horseshoe-shaped headrest and precautions with lateral
      rotation of the head in patients with carotid atheroma.

PMID- 17538356
TI  - The use of C1 lateral mass screws in complex cervical spine surgery: indications,
      techniques, and outcome in a prospective consecutive series of 25 cases.
AB  - OBJECTIVES: Direct C1 lateral mass/C2 pars or pedicle screw fixation has been
      recently proposed as an alternative method to C1-C2 transarticular screw
      fixation. Although this method seems attractive, there are currently limited
      clinical data on the use of this technique for multilevel fixation including
      complex craniocervical reconstructions. The objectives of this study were to
      assess the safety and the clinical/radiographic outcomes in patients undergoing
      cervical spine surgery using C1 lateral mass screws (C1-LMS). METHODS: A
      prospectively accrued database was reviewed to determine initial presentation,
      etiology, operations, complications, and clinical/radiologic outcomes. RESULTS:
      Twenty-five patients with a mean age of 56 underwent fixation with C1-LMS. Mean
      follow-up was 12 months. The indications for using C1-LMS instead of C1-C2
      transarticular screws were: unfavorable bony or vascular anatomy, tumor
      destruction, thoracic kyphosis or cervical hyperlordosis, inability to reduce the
      C1-C2 dislocation intraoperatively and or surgeon preference. Satisfactory
      stability was achieved in all cases with no neurologic or vascular complications.
      In one case, the C1 screws breached the medial cortex. Three patients developed
      transient postoperative C2 neuralgia. One patient had an extended stay in ICU due
      to respiratory issues. CONCLUSIONS: On the basis of our experience, proficiency
      with the use of C1-LMS screw fixation greatly enhances the ability to manage
      complex atlantoaxial or craniocervical pathologies with low morbidity. This
      technique should be considered an excellent adjunct or alternative to
      transarticular screw fixation.

PMID- 17538357
TI  - Perioperative aspects of endoscopic anterior scoliosis surgery: the learning
      curve for a consecutive series of 100 patients.
AB  - The reported benefits of endoscopic versus open scoliosis surgery include
      improved visualization, a muscle sparing approach, reduced pulmonary morbidity,
      reduced pain, and improved cosmesis. Some aspects of the surgical learning curve
      for this technically demanding method have been previously reported; however,
      improvements in other factors with increasing experience have not been
      quantified. This paper presents a series of 100 consecutive endoscopic anterior
      scoliosis corrections performed between April 2000 and February 2006. We report
      changes in the following perioperative factors with increasing experience;
      operative set-up time, operative time, x-ray irradiation time, number of
      instrumented levels, blood loss, intercostal catheter drainage, chest drain
      removal time, days in intensive care, days to mobilize, days in hospital, and
      early complications. Statistical comparisons were made between the first 20 (1 to
      20), middle 20 (41 to 60), and last 20 (81 to 100) cases. Results showed
      statistically significant improvements and increased consistency in operative
      time, operative set-up time, x-ray irradiation time, blood loss, hospital stay,
      and mobilization time with experience. The complication rate was comparable to
      other recently published endoscopic studies. In the last 20 cases of the series,
      operative times had reduced to 35 minutes per level, x-ray irradiation times to
      15 seconds per level, and blood loss to 38 mL per level. Most perioperative
      surgical factors therefore improve significantly with increasing experience in
      endoscopic anterior scoliosis correction.

PMID- 17538358
TI  - Spinal infection in intravenous drug abusers.
AB  - The number of intravenous (IV) drug abusers has been increasing in recent years.
      They are generally younger and healthier than the typical patient with a spinal
      infection. Reviewing the English language literature, there are only a few
      articles discussing the relationship between IV drug abuse and spinal infection.
      We studied 21 IV drug abusers with spinal infection. All were male, 19 were in
      their 30s and 40s with a mean age of 44 years. The mean follow-up period was 41
      months after surgical intervention. Mild and severe neurologic deficit were seen
      in 5 and 13 patients (Frankel Grade C in 5, Grade D in 8), respectively. The
      overall positive culture rate was 17 out of 21 (81%). Twelve patients were
      infected with Staphylococcus aureus and 3 with Pseudomonas aeruginosa. Two had
      Mycobacterium tuberculosis. All were treated with anterior debridement and strut
      bone grafting with or without posterior instrumentation, laminectomy and abscess
      excision, or with additional discectomy. All patients with neurologic deficit
      recovered to a normal status. At the most recent follow-up, all the spine
      segments had fused and no one complained of any recurrent back pain. There were
      no postoperative complications. Physicians need to be more alert to the
      possibility of spinal infection in IV drug abusers with back pain. In addition to
      Staphylococcus aureus, Pseudomonas aeruginosa and Mycobacterium tuberculosis may
      be seen among IV drug abusers.

PMID- 17538359
TI  - Recognizing schwannomatosis and distinguishing it from neurofibromatosis type 1
      or 2.
AB  - BACKGROUND DATA: Schwannomatosis has become a newly recognized classification of
      neurofibromatosis. Although the genetic loci are on chromosome 22, it lacks the
      classic bilateral vestibular schwannomas as seen in NF-2. We present the surgical
      treatment of 4 patients with schwannomatosis, including a brother and sister.
      METHOD: Case 1 presented with multiple progressively enlarging peripheral nerve
      sheath tumors. Case 4 presented with a trigeminal schwannoma and a vagal nerve
      schwannoma. Three of 4 patients had spinal intradural, extramedullary nerve
      sheath tumors. Surgery in all was multistaged and consisted of spinal
      laminectomies, site-specific explorations, and microsurgical tumor dissection and
      resection, with intraoperative neurophysiologic monitoring (including
      somatosensory-evoked and motor-evoked potentials, upper extremity
      electromyography and intraoperative nerve action potential monitoring, as
      appropriate). RESULTS: Intraoperatively the schwannomas had cystic and solid
      features and in all surgical cases the tumors arose from discrete fascicles of
      sensory nerve roots or sensory peripheral nerve branches. None of the patients
      experienced neurologic worsening as a result of their resections. Pathologic
      analysis of specimens from all cases demonstrated schwannoma. CONCLUSIONS: Not
      all patients with multiple schwannomas of cranial nerve, spinal nerve root, or
      peripheral nerve origin have NF-1 or NF-2. In schwannomatosis, these lesions are
      present in the absence of cutaneous stigmata, neurofibromas, vestibular
      schwannomas, or parenchymal brain tumors. Schwannomas in schwannomatosis can be
      large, cystic, and multiple. However, the predominant nerve involvement seems to
      be sensory and discrete fascicular in origin, facilitating microsurgical
      resection with minimal deficit.

PMID- 17538360
TI  - Repeated meningitis as a delayed complication of scoliosis surgery.
AB  - STUDY DESIGN: Case report. OBJECTIVE: To report a case of very delayed repeated
      meningitis after surgical treatment of scoliosis. SUMMARY OF BACKGROUND DATA:
      Delayed infection after spine surgery is a well-reported phenomenon, presenting
      usually with local wound symptoms and back pain. The occurrence of meningitis
      after spinal instrumentation is reported but not common. Delayed repeated
      episodes of meningitis after surgical treatment of scoliosis have never been
      reported. CASE REPORT: We report a case of a 44-year-old gentleman, submitted to
      surgical treatment of scoliosis years ago, who presented with repeated episodes
      of meningitis due to the formation of an abnormal communication between an
      infected cyst in the bone cavity where the rods were located and the intradural
      space in the lumbar spine. Computerized tomography and magnetic resonance imaging
      revealed the presence of a bone cyst with thickened layering, and surgical
      exploration revealed the communication between this cystic cavity and the
      intradural space. After surgical closure of the dural space and cleaning of the
      cyst, the patient responded well to antibiotic therapy and was free of new
      episodes of meningitis up to the last follow-up, 1 year after the surgical
      treatment. Clinical diagnosis of delayed postoperative infection in spine surgery
      may be difficult if no wound signs are present. Clinical symptoms vary and may
      include increased back pain, wound redness, swelling and drainage, elevated
      erythrocyte sedimentation rate and white blood count, fever, and malaise.
      CONCLUSIONS: Delayed meningitis can be a late complication of spinal
      instrumentation for scoliosis. A high index of suspicion is necessary.

PMID- 17538362
TI  - A recurrent craniopharyngioma illustrates the potential usefulness of urinary
      matrix metalloproteinases as noninvasive biomarkers: case report.
AB  - OBJECTIVE: Matrix metalloproteinases (MMPs) are a class of enzymes involved in
      angiogenesis, tumor growth, and metastasis. Recent reports indicate that urinary
      MMPs predict the presence of several types of tumors, including those of the
      breast, prostate, and bladder. Ongoing protocols at our institution are
      evaluating the efficacy of urinary MMPs as diagnostic markers for brain tumors
      and gastrointestinal disease. CLINICAL PRESENTATION: An 8-year-old girl underwent
      transsphenoidal resection of a craniopharyngioma at the age of 6 years with
      radiographic gross total resection. Two years later, her urine was analyzed for
      MMPs as part of an evaluation for gastrointestinal complaints. Despite normal
      gastrointestinal evaluation results, her urinary MMP levels were markedly
      elevated. She subsequently sought treatment for recurrent craniopharyngioma.
      INTERVENTION: The craniopharyngioma was resected again. Approximately 1 year
      after surgery, no sources of the elevated MMPs have been found other than the
      recurrent craniopharyngioma. Follow-up analysis of urinary MMPs demonstrated
      clearing of markers concordant with tumor treatment. CONCLUSION: We report the
      finding of elevated urinary MMPs in the setting of a recurrent craniopharyngioma.
      These biomarkers correlate with the presence of disease, clear with treatment,
      and can be tracked from source tissue to urine. The findings of this case support
      the hypothesis that urinary MMPs may be a useful predictor of the presence or
      recurrence of brain tumors. To our knowledge, this is the first report supporting
      the proof-of-principle concept that urinary MMPs may have potential usefulness in
      predicting the presence of brain tumors, expanding the spectrum of tumors capable
      of being diagnosed with this technique.

PMID- 17538363
TI  - Cerebellopontine angle cyst compressing the vagus nerve: case report.
AB  - OBJECTIVE: The cerebellopontine angle (CPA) is a rare location for an arachnoid
      cyst. We describe a patient with a CPA arachnoid cyst who presented with
      hoarseness (unilateral vocal cord paralysis) and dysphagia secondary to isolated
      compression of the vagus nerve. This rare presentation of a CPA arachnoid cyst
      has not been reported previously. CLINICAL PRESENTATION: The patient described is
      a 50-year-old man who experienced a precipitous onset of hoarseness and
      dsyphagia. An otolaryngological evaluation revealed right-sided vocal cord
      paralysis. Brain magnetic resonance images displayed a cystic mass at the right
      CPA and anterior displacement of the vagus nerve. INTERVENTION: The patient
      underwent retrosigmoidal craniectomy with cyst fenestration, which was well
      tolerated. Intraoperatively, Cranial Nerve X was found splayed over the cyst and
      was consequently decompressed. CONCLUSION: Postoperatively, the patient's
      dysphagia completely resolved. However, the results of a laryngeal
      electromyocardiogram revealed minimal evidence of recovery in the affected vocal
      fold, and the patient continued to suffer from dysphonia. Although CPA arachnoid
      cysts are rare, they should be considered when a patient presents with an
      isolated cranial nerve palsy. Treatment options include cyst fenestration and
      cranial nerve decompression.

PMID- 17538364
TI  - Cervical tumoral calcium pyrophosphate dihydrate deposition disease 28 years
      after suboccipital craniotomy: case report.
AB  - OBJECTIVE: To describe a rare case of tumoral cervical chondrocalcinosis that
      appeared 28 years after the patient had undergone suboccipital craniotomy.
      CLINICAL PRESENTATION: A 42-year-old woman suffered from cervicalgia associated
      with a firm mass at the occipitocervical region. Plain x-ray and computed
      tomographic and magnetic resonance images revealed a calcified lesion in a scar
      from a previous suboccipital craniotomy. INTERVENTION: The patient underwent
      tumorectomy and histopathology, which revealed an exuberant tumoral
      chondrocalcinosis. Laboratory test results revealed no secondary cause for the
      chondrocalcinosis. CONCLUSION: Identification of chondrocalcinosis beyond the
      cervical region is very rare. Localization of chondrocalcinosis in a scar from a
      previous suboccipital craniotomy has not been previously reported. Surgery
      appears to be the treatment of choice for this form of chondrocalcinosis.

PMID- 17538365
TI  - Intraosseous spinal glomus tumors: case report.
AB  - OBJECTIVE: Glomus tumors are rare lesions that can arise intraosseously along the
      entire spinal axis. Only four cases have been reported, usually manifesting with
      severe back pain and involving the midthoracic spine or sacrum. The current
      report describes the largest such lesion reported in the literature to date and
      summarizes the clinical and pathological characteristics of these rare tumors.
      METHODS: A single, recent case arising from the lumbar vertebra of L3 is
      described, and the literature of intraosseous spinal glomus tumors is reviewed.
      RESULTS: The lesion described arose in a 44-year-old man with a 1-year history of
      neurological symptoms and a large dumbbell-shaped lesion involving the lumbar
      vertebra, which extended through the neural foramen at L3. The lesion was
      resected using a two-stage approach. Severe intraoperative hemorrhage
      necessitated emergent angiographic embolization. Histopathological examination
      confirmed the presence of a glomus tumor arising from the smooth muscle cells of
      the glomus body. CONCLUSION: These rare lesions may extend into the epidural
      space and through the neural foramina and abdominal compartments; over time, they
      grow very large. Preoperative embolization may be indicated for large tumors
      suspected to be glomus tumors.

PMID- 17538368
TI  - Spinal cord injuries entering the Fas(t) lane.

PMID- 17538369
TI  - Athletic concussion: current understanding as of 2007.

PMID- 17538370
TI  - Petroclival meningiomas: multimodality treatment and outcomes at long-term follow
      up.
AB  - OBJECTIVE: To evaluate patients' clinical outcome, survival, and performance
      status, at the long-term follow-up evaluation after aggressive microsurgical
      resection of petroclival meningiomas. METHODS: During a 13-year period (1991
      2004), 150 patients underwent 207 operative procedures for resection of
      petroclival meningiomas. The tumor size was large in 79% of the patients, with a
      mean tumor diameter of 3.44 cm. Tumors extended into adjoining regions in 57% of
      the patients. Thirty patients (20%) previously underwent operation or
      irradiation. One hundred patients (66%) had a single operation, 43 patients (29%)
      had two operations, and seven patients (5%) had three operations. Gross tumor
      resection was accomplished in 48 patients (32%), subtotal resection in 65
      patients (43%), and partial resection in 37 patients (25%). There were no
      operative deaths. Postoperative complications (cerebrospinal fluid leakage,
      quadriparesis, infections, cranial nerve palsies, etc.) were observed in 33
      patients (22%). Postoperative radiation or radiosurgery was administered to 47 of
      the 102 patients who had residual tumors. The outcome and survival of patients
      were evaluated by questionnaires, telephone calls, and review of their recent
      radiological images. RESULTS: At the conclusion of the study, 87 patients (58%)
      were alive with disease and 45 patients (30%) were alive without disease. The
      mean follow-up period was 102 months (range, 15-180 mo). Seven patients (5%; five
      of the subtotal and partially resected patients and two of the total resection
      patients) had recurrence; of these patients, two underwent repeat resection and
      four were treated with gamma knife radiosurgery. One of the patients died of
      tumor progression with no response to gamma knife radiosurgery. The recurrence
      free survival rate was 100% at 3 years, 92.7% at 7 years, and 85% at 12 years;
      the progression-free survival rate was 96% at 3 years, 86.8% at 7 years, and
      79.5% at 12 years. The Karnofsky Performance Scale score was 78 +/- 11
      preoperatively, 76 +/- 11 at 1 year postoperatively, and 84 +/- 9 at the time of
      the latest follow-up evaluation. Common disabilities at the time of the follow-up
      evaluation included diplopia, loss of hearing, balance problems, and loss of
      sensation in the V1 and V2 cranial nerve distribution. Most patients developed
      coping mechanisms. CONCLUSION: This series has the largest number of patients
      with the longest follow-up period, to our knowledge, reported in the literature
      to date. The excellent quality of life at the time of the long-term follow-up
      examination for these patients warrants aggressive but judicious tumor resection,
      with or without radiosurgical treatment of tumor remnants.

PMID- 17538371
TI  - Effects of using combined transpetrosal surgical approaches to treat petroclival
      meningiomas.
AB  - OBJECTIVE: Surgical treatment may be required for large petroclival meningiomas;
      however, surgery for these lesions is a major undertaking, and modern surgical
      approaches are still associated with considerable morbidity and recurrence rates.
      We analyzed our series of transpetrosally operated petroclival meningiomas to
      obtain detailed information regarding the surgery outcomes with respect to facial
      nerve effects, hearing changes, general neurological and psychosocial
      differences, and recurrence rates to identify opportunities for improvement.
      METHODS: Between 1994 and 2004, we used transpetrosal approaches to operate on 29
      patients for petroclival meningiomas larger than 30 mm. All patients were
      analyzed in detail regarding neurological outcomes and hearing abilities after
      surgery. Swedish-speaking patients were contacted for a psychosocial follow-up
      evaluation using the short-item 36 (SF-36) form. RESULTS: After surgery, the
      Glasgow Outcome Score improved in 14 patients, was unchanged in 11 patients, and
      worsened in four patients. Facial nerve function was found to be of House
      Brackmann Grade 3 or worse in six patients (including three individuals with
      transcochlear surgery and facial nerve rerouting). Of the 23 patients who
      underwent hearing-preservation surgery, serviceable hearing was preserved in 17
      individuals. Nineteen Swedish patients were contacted for psychosocial
      evaluation. Three patients could not participate for health reasons; of the
      remaining 16 patients, 12 reported physical health scores that were below mean
      values for the general population. For patients who did not experience very
      serious neurological compromise, we found that unexpected painful trigeminal
      neuropathy and unilateral swallowing difficulties conveyed a negative influence
      on health. Three years after surgery, the patients reported more normalized
      health scores. CONCLUSION: Generally, outcomes compared well with current
      reports. Outcomes can be improved, however by improving patients' psychosocial
      support; striving to decompress, preserve, and minimize dissection of ill-defined
      planes of cranial nerves; and using Simpson Grade 4 gamma knife approaches when
      radicality is precluded. Currently, the performance of transpetrosal surgery for
      petroclival meningiomas is a major undertaking that significantly affects a
      patient's health for several years; however, the approaches that we used allowed
      a high degree of tumor control with relatively little neurological morbidity.

PMID- 17538372
TI  - Surgical treatment of giant pituitary adenomas: strategies and results in a
      series of 95 consecutive patients.
AB  - OBJECTIVE: Giant pituitary adenomas, defined as those measuring at least 4 cm in
      maximum diameter, are a therapeutic challenge. We report our experience in a
      large, consecutive series of patients with giant adenomas. METHODS: Between 1990
      and 2004, 95 patients with a giant pituitary adenomas underwent surgery at our
      department. Nonfunctioning pituitary adenoma was the most frequent type (n = 70;
      73.7%), whereas hormone-secreting adenomas numbered only 25 (26.3%). The mean age
      at the time of surgery (+/-standard error of the mean) was 48.4 +/- 1.5 years;
      there were 66 men (69.5%) and 29 women (20.5%). RESULTS: In total, 111 surgical
      procedures were performed. Of these, 85 approaches (76.6%) were transsphenoidal
      and 26 (23.4%) were transcranial. Visual improvement occurred in 59 of the 79
      patients with preoperative defect who could be evaluated after surgery (74.7%).
      Radical tumor excision was obtained in 14 patients (14.7%). Adjuvant medical and
      radiation therapies led to 74.5% (95% confidence interval, 62.7-86.4%) control of
      tumor growth at 5 years. This was not different in patients with nonfunctioning
      pituitary adenomas compared with patients with hormone-secreting tumors. In the
      subgroup of patients with nonfunctioning pituitary adenomas, radiation therapy
      had a protective role against tumor growth (P < 0.01). CONCLUSION: Maximal
      surgical removal of giant adenomas through the transsphenoidal or transcranial
      approach, or both, aimed to relieve compression of the optic pathway and reduce
      tumor volume as much as possible, offers the best chances to control the tumor
      when followed with adjuvant medical and radiation therapies.

PMID- 17538373
TI  - Arteriovenous malformations after Leksell gamma knife radiosurgery: rate of
      obliteration and complications.
AB  - OBJECTIVE: Although relevant information exists regarding the chance of
      obliterating arteriovenous malformations (AVMs) using radiosurgery, the overall
      chance of cure after gamma knife radiosurgery is usually only extrapolated from a
      portion of all monitored patients. This chance and the risks involved in
      radiosurgery, including repeat treatment when necessary in a defined population
      of treated patients, were analyzed in our study. METHODS: Between October 1992
      and June 2000, gamma knife radiosurgery was performed on 330 patients with AVMs.
      The volume of the AVM nidus ranged from 0.15 to 28.6 cm (median, 3.9 cm). When
      complete obliteration was not achieved within 3 years, repeat radiosurgery was
      performed on 76 patients. The volume of the nidus for the second treatment ranged
      from 0.09 to 16.8 cm (median 2.9 cm). The result was reviewed in 300 (91%)
      patients after the first round of treatment and in 68 (89.5%) after the second
      round of treatment. RESULTS: AVM obliteration was achieved in 222 (74%) patients
      after the first round of radiosurgery and in 47 (69%) after the second. The
      overall chance of cure was 92% (269 patients). Final angiography verified
      complete obliteration by 12 to 96 months (median, 25 mo) after initial
      radiosurgery. Smaller volume AVMs and the application of a higher radiation dose
      resulted in a higher chance of obliteration. The risk of rebleeding after
      radiosurgery was 2.1% annually until full obliteration, and the overall mortality
      from rebleeding was 1%. The risk of permanent morbidity after the first and
      second radiosurgery treatments were 2.7 and 2.9%, respectively. The cumulative
      risk of morbidity in both groups of patients was 3.4%. CONCLUSION: Although one
      quarter of the patients required that the treatment be repeated, gamma knife
      radiosurgery can offer a high cure rate for patients treated for AVMs with a low
      risk of morbidity and mortality from rebleeding during the latent period.

PMID- 17538374
TI  - The Stockholm 20-year follow-up of aneurysmal subarachnoid hemorrhage outcome.
AB  - OBJECTIVE: To assess the clinical and radiological long-term outcome after
      aneurysmal subarachnoid hemorrhage (SAH) in a defined referral area regarding
      recurrent SAH and de novo aneurysm formation. METHODS: One hundred and two 1-year
      survivors after aneurysmal SAH, who were treated at the Neurosurgical Clinic,
      South Hospital, Stockholm, Sweden, between 1983 and 1985, were followed for 20
      years. Forty-nine surviving patients were reevaluated. Hospital records and death
      certificates were scrutinized for all 53 nonsurviving patients. Clinical history
      penetration, Mini Mental Status, Rankin Disability Score, and Barthel Index were
      used to evaluate the outcome. Computed tomographic angiography was used to
      investigate the cerebral arteries. RESULTS: One hundred and two patients were
      traced. Fifty-three patients were deceased. One patient had a hospital record of
      sustaining an aneurysmal SAH from a known but not clipped aneurysm. Three
      patients had nonaneurysmal intracerebral hemorrhage and two sustained traumatic
      SAH. There were 49 surviving patients. Six refused follow-up. None of these
      patients had hospital records of intracranial disease. Three of the 43 remaining
      patients could not be tested. None of the survivors had experienced a new SAH.
      Aneurysm base remnants were observed in 1% (eight patients, 790 person-years of
      follow-up) and de novo aneurysms were observed in 0.9% (seven patients, 790
      person-years of follow-up). CONCLUSION: From this epidemiological survey of
      patients with aneurysmal SAH, it was found that none of the patients experienced
      a recurrent subarachnoid bleed from the treated aneurysm during a 20-year follow
      up period. Thus, a routine extreme long-term follow-up period is not necessary.
      De novo aneurysm formation and possible enlargements of aneurysm base remnants
      were observed in almost 2% of patients per person year and should, therefore, be
      subject of a routine, long-term follow-up.

PMID- 17538375
TI  - Midterm clinical and magnetic resonance imaging follow-up of large and giant
      carotid artery aneurysms after therapeutic carotid artery occlusion.
AB  - OBJECTIVE: The purpose of this study was to evaluate aneurysm size and clinical
      symptoms midterm after therapeutic carotid artery occlusion in 39 patients with
      large or giant carotid artery aneurysms. METHODS: Between January 1996 and August
      2004, 39 patients with large or giant carotid artery aneurysms were treated with
      therapeutic carotid artery occlusion and had clinical and magnetic resonance
      imaging follow-up of at least 3 months (mean, 35.9 mo; median, 29 mo; range, 3
      107 mo; 117 patient-yr). Initial clinical presentation was mass effect caused by
      the aneurysm in 32 (82%) of the 39 patients. Three patients presented with
      subarachnoid hemorrhage and one presented with epistaxis; two aneurysms were an
      incidental finding and one was additional to another ruptured aneurysm. RESULTS:
      There were no early or late complications of therapeutic carotid artery
      occlusion. All aneurysms seemed to have thrombosed completely after carotid
      artery occlusion as observed on early and late magnetic resonance imaging and
      magnetic resonance angiographic follow-up studies. At the time of the most recent
      magnetic resonance imaging follow-up study, 29 (74%) of the 39 aneurysms
      involuted totally, two aneurysms decreased to 25% of the original diameter, two
      aneurysms decreased to 50%, and five aneurysms decreased to 75%. Two aneurysms
      remained unchanged in size after 49 and 58 months, respectively. At the most
      recent clinical follow-up evaluation, symptoms of mass effect were cured in 19
      (60%), improved in 10 (31%), and remained unchanged in three (9%) of the 32
      patients. CONCLUSION: Therapeutic carotid artery occlusion was a simple, safe,
      and effective treatment for large and giant carotid artery aneurysms. Almost all
      aneurysms involute completely or substantially decrease in size. Alleviation of
      symptoms of mass effect was achieved in most patients.

PMID- 17538378
TI  - Complications of lumboperitoneal shunts.
AB  - OBJECTIVE: Placement of a lumboperitoneal (LP) shunt is a method for treating
      communicating hydrocephalus. These shunts can be placed with or without valves.
      We sought to review the complications associated with the use of LP shunts with
      the increasing use of horizontal-vertical (HV) valve systems. PATIENTS AND
      METHODS: A retrospective chart review of all patients who received LP shunts at
      University of California, San Francisco from 1998 to 2005 was performed. RESULTS:
      Of the 74 patients identified in this study, 67 underwent LP shunt placement for
      the first time, and seven patients had revisions of LP shunts that were
      originally placed at another hospital. There were a total of 44 revisions for the
      entire group: 27 patients had one revision, 10 patients had two or three
      revisions, and one patient had five revisions. Obstruction or migration of the
      peritoneal catheter was the most common reason for revision. The HV valve was
      responsible for shunt malfunction in nine patients and was the second-most common
      site of system problems. Overdrainage symptoms were observed in 11 patients, most
      of whom had LP shunts without any valve. No patients with an HV valve system
      developed an acquired Chiari malformation. There were three cases of infection,
      two of which required removal of the LP shunt. CONCLUSION: Overall, the placement
      of LP shunts for the treatment of communicating hydrocephalus seems to be a safe
      procedure. Serious complications such as subdural hematoma were not observed. The
      HV valve was associated with minor complications, but it was effective in
      reducing the incidence of overdrainage.

PMID- 17538376
TI  - Transvenous embolization of dural carotid-cavernous fistulae with transfacial
      catheterization through the superior ophthalmic vein.
AB  - OBJECTIVE: We report our experience gaining access to the cavernous sinus via
      transfacial catheterization of the superior ophthalmic vein through the angular
      or retromandibular vein. We evaluate the viability of this approach as a safe and
      convenient alternative pathway for transvenous embolization of the cavernous
      sinus. METHODS: This is a retrospective study of 98 patients with symptomatic
      dural carotid-cavernous fistulae from two major regional hospitals in Hong Kong.
      All 98 patients presented with one or more ocular symptoms. Seventy-four
      transvenous embolization procedures were performed on 71 patients. Transvenous
      access to the cavernous sinus was attempted through various pathways, one by one,
      until the cavernous sinus was successfully catheterized. RESULTS: The overall
      technical success rate of transvenous embolization of dural carotid-cavernous
      fistulae in our study was 64 out of 74 patients (86.5%). Had we not used the
      technique of transfacial catheterization, the technical success rate would have
      been 53 out of 74 patients (71.6%). After adoption of the transfacial approach,
      the technical success rate of transvenous embolization became 64 out of 64
      patients (100%). Residual symptoms occurred in eight patients. Two patients
      developed transient VIth cranial nerve palsy after transvenous embolization for 1
      and 2 months, respectively. Otherwise, there were no complications. CONCLUSION:
      Transfacial catheterization through the superior ophthalmic vein is a safe and
      effective approach and provides a convenient alternative pathway for transvenous
      embolization of dural carotid-cavernous fistulae when cannulation of the inferior
      petrosal sinus is not successful, thereby increasing the technical success rate.

PMID- 17538377
TI  - Stereotactic ventriculoperitoneal shunting for refractory idiopathic intracranial
      hypertension.
AB  - OBJECTIVE: Recent reports have shown promising short- to medium-term results in
      patients with refractory idiopathic intracranial hypertension (IIH) treated using
      the stereotactic ventriculoperitoneal shunting (SVPS) technique. However, the
      long-term clinical efficacy of this technique remains questionable. This report
      provides the long-term results of SVPS in treating refractory IIH patients.
      METHODS: We reviewed the medical charts of nine consecutive patients (mean age,
      26.4 yr; range, 4-63 yr) treated using either a frame-based or frameless SVPS
      technique for IIH. RESULTS: The mean postoperative follow-up period was 44.3
      months (range, 6-110 mo). Before shunting procedures were performed, each patient
      presented with intractable headache, and five patients (55.6%) had mild to
      moderate visual deficits. The last follow-up assessment showed that after
      shunting was performed, eight patients (89%) were headache-free. Only one patient
      had recurrent headache; however, this patient's pain was much less frequent and
      severe than before the shunting procedure was completed and was concomitant with
      recent weight increase. Visual deficits were resolved in three patients and
      remained stable in two who already had optic nerve atrophy before shunting was
      completed. Twelve SVPS procedures were performed on our patients. Nine shunt
      revisions were needed in six patients because of infection (n = 5, including two
      revisions in one patient), valve dysfunction (n = 2), distal obstruction (n = 1),
      and ventricular catheter malpositioning (n = 1). No patient had proximal catheter
      obstruction. CONCLUSION: Given the favorable long-term outcome of the SVPS
      technique for refractory IIH, we are encouraged to apply this procedure on our
      patients. More invasive approaches should be reserved for patients who have SVPS
      failure.

PMID- 17538379
TI  - Sensitivity of the concussion assessment battery.
AB  - OBJECTIVE: Sports medicine clinicians commonly use multiple tests when evaluating
      patients with concussion. The specific tests vary but often include symptom
      inventories, posturography, and neurocognitive examinations. The sensitivity of
      these tests to concussion is vital in reducing the risk for additional injury by
      prematurely returning an athlete to play. Our study investigated the sensitivity
      of concussion-related symptoms, a postural control evaluation, and neurocognitive
      functioning in concussed collegiate athletes. METHODS: From 1998 to 2005, all
      high-risk athletes completed a baseline concussion-assessment battery that
      consisted of a self-reported symptom inventory, a postural control evaluation,
      and a neurocognitive assessment. Postconcussion assessments were administered
      within 24 hours of injury to 75 athletes who had physician-diagnosed concussion.
      Individual tests and the complete battery were evaluated for sensitivity to
      concussion. RESULTS: The computerized Immediate Post-Concussion Assessment and
      Cognitive Testing and HeadMinder Concussion Resolution Index (neurocognitive
      tests) were the most sensitive to concussion (79.2 and 78.6%, respectively).
      These tests were followed by self-reported symptoms (68.0%), the postural control
      evaluation (61.9%), and a brief pencil-and-paper assessment of neurocognitive
      function (43.5%). When the complete battery was assessed, sensitivity exceeded
      90%. CONCLUSION: Currently recommended concussion-assessment batteries accurately
      identified decrements in one or more areas in most of the athletes with
      concussion. These findings support previous recommendations that sports-related
      concussion should be approached through a multifaceted assessment with components
      focusing on distinct aspects of the athlete's function.

PMID- 17538380
TI  - Microsurgical treatment of symptomatic sacral perineurial cysts.
AB  - OBJECTIVE: The aim of this study was to investigate the microsurgical results of
      symptomatic sacral perineurial cysts of 11 patients and to discuss the treatment
      options of the past 10 years. METHODS: We retrospectively reviewed the records of
      11 patients with symptomatic sacral perineurial cysts who underwent microsurgical
      treatment at Tongji Hospital, Huazhong University of Science and Technology from
      1993 through 2006. The philosophy was to perform total or partial cyst wall
      removal, to imbricate the remaining nerve sheath if possible, and to repair local
      defect with muscle, Gelfoam (Pharmacia & Upjohn, Kalamazoo, MI), and fibrin glue.
      Patient outcomes were assessed by comparing the preoperative and postoperative
      examination results. The average follow-up time obtained from return visits to
      the neurosurgery clinic or by telephone questionnaires ranged from 2 months to 13
      years. A literature search and analysis of current treatment options were
      performed. RESULTS: Nine of the 11 patients (82%) experienced complete or
      substantial relief of their preoperative symptoms. One patient (Patient 4)
      experienced worsening of bladder dysfunction after surgery and recovered slowly
      to subnormal function during the subsequent 2 months. The symptoms of Patient 9
      did not resolve, and magnetic resonance imaging showed that the cyst had
      reoccurred. The patient underwent reoperation 3 months later without any
      improvement. One patient (Patient 11) experience a cerebrospinal fluid leakage
      complication. Neither new postoperative neurological defects nor infection were
      observed in our series. In the literature, there are six different treatment
      options under debate and controversially discussed. CONCLUSION: Microsurgical
      treatment yielded the best long-term resolution of patient symptoms to date and
      should be recommended to appropriately selected patients.

PMID- 17538381
TI  - Concentration of malondialdehyde-modified low-density lipoprotein in the jugular
      bulb during carotid endarterectomy correlates with development of postoperative
      cognitive impairment.
AB  - OBJECTIVE: Approximately 20 to 30% of patients undergoing carotid endarterectomy
      (CEA) subsequently develop cognitive impairment. The purpose of the present study
      is to determine whether or not malondialdehyde (MDA)-modified low-density
      lipoprotein (LDL), a biochemical marker of oxidative damage, concentrations in
      the jugular bulb during CEA correlates with development of postoperative
      cognitive impairment. METHODS: Fifty-five patients undergoing CEA were assessed
      with a battery of neuropsychological tests before and 1 month after surgery.
      Serum samples for measurement of MDA-LDL concentration were obtained from a
      venous catheter inserted into the ipsilateral jugular bulb at the following time
      points: immediately before clamping of the internal carotid artery (ICA), 10
      minutes after clamping of the ICA, and 5 and 20 minutes after declamping of the
      ICA. RESULTS: The MDA-LDL concentrations at 5 and 20 minutes after ICA declamping
      were both significantly higher than concentrations before ICA clamping (P <
      0.0001). At the postoperative neuropsychological assessment, six (11%) out of 55
      patients showed postoperative cognitive impairment. Logistic regression analysis
      demonstrated that higher values of MDA-LDL increase (calculated as a percentage
      of the preclamp values) at either 5 or 20 minutes after ICA declamping were
      significantly associated with the development of postoperative cognitive
      impairment (95% confidence interval, 0.787-0.981; P = 0.0209) among the variables
      tested. CONCLUSION: MDA-LDL concentration in the jugular bulb during CEA
      correlates with development of postoperative cognitive impairment.

PMID- 17538382
TI  - Prospective error recording in surgery: an analysis of 1108 elective
      neurosurgical cases.
AB  - OBJECTIVE: Surgical error is common and contributes to complications for
      patients, necessitating detailed prospective collection and analysis of error
      data that emphasizes prevention. METHODS: One neurosurgeon prospectively recorded
      errors and complications for consecutive patients undergoing elective
      neurosurgical procedures. Each error was scored for type, severity,
      preventability, and consequence. RESULTS: Between May 2000 and August 2006, 1108
      elective cases were studied, comprising 76.1% cranial, 22.7% spinal, and 1.2%
      other procedures. There were 2684 errors in 87.1% of cases. The most common
      errors were technical (27.8%), contamination (25.3%), equipment failure or
      missing equipment (18.2%), or related to delay (12.5%). Of the errors, 22.6% were
      considered major and 77.4% were minor, with 2.7% of errors substantially
      impacting the clinical course of the patient. Of all errors, 78.5% were deemed
      preventable. Of the complications, 16.7% were related to errors, of which 80.6%
      were major errors. Of the error-related complications, 74.2% were declared
      preventable. A propensity for error was identified with cranial procedures and
      patients with higher American Society of Anesthesiologists scores (P < 0.01).
      CONCLUSION: Surgical errors are common, often preventable, and frequently lead to
      clinical impact. In addition, the type of procedure and characteristics of the
      patient are important factors to consider when addressing surgical error. For
      individual surgeons to maintain quality control and contribute to the safety of
      the health care system, they must track and analyze errors to ensure that systems
      may be developed to prevent their occurrence.

PMID- 17538383
TI  - An invasion of the atlas.

PMID- 17538384
TI  - Transplantation of stem cells from the adult human brain to the adult rat brain.
AB  - OBJECTIVE: To investigate the migration, proliferation, and differentiation of
      stem cells and neural progenitor cells (NPCs) from the adult human brain after
      transplantation into adult rodent brains. METHODS: Adult human NPCs were obtained
      from temporal lobe specimens removed because of medical intractable epilepsy. The
      cells were transplanted into the posterior periventricular region above the
      hippocampus in the brains of either healthy adult rats (control) or rats with
      selective injury of the hippocampal CA1 region (global ischemia). RESULTS: In the
      control animals, grafted cells were mainly distributed from the site of
      transplantation toward the midline along white matter tracts. The density of
      transplanted cells elsewhere, including the hippocampus, was low and apparently
      random. In animals with CA1 damage, NPCs showed targeted migration into the
      injured area. Cell survival at 10 weeks was 4.7 +/- 0.3% (control, n = 3) and 3.7
      +/- 1.1% (ischemia, n = 3); at 16 weeks, cell survival was 3.4 +/- 0.6% (control,
      n = 2) and 7.2 +/- 1.5% (ischemia, n = 2), i.e., comparable to what has been
      observed earlier when transplanting embryonic tissue into the human brain or
      progenitor cells between inbred rats. The number of dividing cells decreased with
      time. Sixteen weeks after transplantation, 4 +/- 1% (n = 4) of the cells showed
      proliferative activity. We did not observe signs of tumor formation or aberrant
      cell morphology. Neuronal differentiation was much slower than what has been
      observed earlier in vitro or after transplantation to the developing nervous
      system, and 16 weeks after transplantation many surviving cells were still in
      maturation. CONCLUSION: The present study shows that adult human NPCs survive,
      show targeted migration, proliferate, and differentiate after grafting into the
      adult rat brain.

PMID- 17538385
TI  - Characterization of the endothelin-B receptor expression and vasomotor function
      during experimental cerebral vasospasm.
AB  - OBJECTIVE: Several investigations suggest a key role of endothelin (ET) in the
      development of cerebral vasospasm (CVS). In the cerebrovasculature,
      physiologically ET-dependent constriction is mediated by the ET(A) receptor,
      whereas activation of the endothelial ET(B) receptor results in relaxation.
      However, existence of a contractile ET(B) receptor was postulated after
      subarachnoid hemorrhage (SAH), according to gene expression studies. The aim of
      the present investigation is, therefore, to characterize the function and the
      expression of the ET(B) receptor in the cerebrovasculature during CVS. METHODS:
      CVS was induced in the rat double-hemorrhage model and assessed by perfusion
      weighted magnetic resonance imaging scans. Rats were sacrificed on Days 3 and 5
      after SAH, and immunohistochemical staining for ET(B) receptors was performed.
      Isometric force of basilar artery ring segments with (E+) and without (E-)
      endothelial function was measured. Concentration effect curves for the ET(B)
      receptor agonist, sarafotoxin 6c, were constructed by cumulative application in
      segments under resting tension and after precontraction. RESULTS:
      Immunoreactivity for the ET(B) receptor was observed exclusively in the
      endothelium and was not significantly altered after SAH. Under resting tension,
      sarafotoxin 6c did not induce significant contraction in E+ or E- segments. After
      precontraction, a significant relaxation was induced by sarafotoxin 6c
      administration in sham-operated rats (mean maximum effect, 103 +/- 10%), which
      decreased time dependently after SAH (Day 3, 68 +/- 3%; Day 5, 42 +/- 3%).
      Endothelium-dependent relaxation induced by acetylcholine, however, was not
      significantly reduced. CONCLUSION: The present investigation provides evidence
      for the loss of the ET(B) receptor-mediated vasomotor function after SAH. Thus,
      antagonism of the ET(B) receptor may be undesirable for the treatment of CVS.

PMID- 17538386
TI  - The adenosine 2A receptor agonist ATL-146e attenuates experimental
      posthemorrhagic vasospasm.
AB  - OBJECTIVE: Selective adenosine 2A receptor agonists, such as ATL-146e, are known
      to be potent anti-inflammatory agents devoid of systemic side effects and have
      been used clinically in a number of disease states. However, adenosine 2A
      receptor agonists have not been studied in the treatment of cerebral vasospasm
      after subarachnoid hemorrhage. The present study investigated the efficacy of ATL
      146e in the prevention of leukocyte infiltration and attenuation of
      posthemorrhagic vasospasm. METHODS: The rodent femoral artery model of vasospasm
      was used. Forty male Sprague-Dawley rats were randomly assigned to four different
      groups (vehicle, 1 ng/kg/min, 10 ng/kg/min, or 100 ng/kg/min ATL-146e
      administered via subcutaneous osmotic minipump). Vasospasm was evaluated at
      posthemorrhage Day 8 (period of peak constriction) by calculating the lumen cross
      sectional area (expressed as percent change in luminal area: ratio of blood
      exposed vessel to normal saline-exposed vessel) and radial wall thickness.
      Immunostaining with anti-CD45 monoclonal antibody to detect leukocytes was used
      to evaluate localized inflammation. RESULTS: Significant vasospasm was noted in
      the vehicle-treated (blood-exposed) control group (78.5%, P < 0.001; expressed as
      a ratio of luminal area of the saline [no blood] control), but not in the ATL
      146e-treated groups (lumen ratio to control: 105.0, 83.4, and 91.3% for the 1,
      10, and 100 ng/kg/min groups, respectively). Additionally, infiltration of
      inflammatory cells was reduced significantly and radial wall thickness was
      decreased in the ATL-146e-treated groups compared with the vehicle-treated
      control group. CONCLUSION: Selective activation of the adenosine 2A receptor with
      ATL-146e prevented posthemorrhagic vasospasm and reduced leukocyte infiltration
      in this experimental model. This agent is worthy of further investigation and
      lends credence to the hypothesis supporting a role for inflammation in the
      pathogenesis of cerebral vasospasm after subarachnoid hemorrhage.

PMID- 17538387
TI  - Preliminary investigation of calcium alginate gel as a biocompatible material for
      endovascular aneurysm embolization in vivo.
AB  - OBJECTIVE: We sought to expand our assessment of calcium alginate as an embolic
      agent in an aneurysm model in swine that survived from 30 to 90 days. The
      objective of this study was to assess the biocompatibility and stability of
      calcium alginate in aneurysms in vivo. METHODS: Ten models were created from a
      venous pouch sutured to the carotid artery, simulating flow to a side-wall
      aneurysm. Eight swine received complete embolizations, and two were less than 50%
      embolized to be used as controls. Alginate and calcium chloride were injected
      from concentric-tube microcatheters to form a mass that filled the aneurysm
      pouch. RESULTS: Angiography and histology verified complete aneurysm occlusion
      and neck healing up to 90 days in eight swine. Both control animal aneurysms
      ruptured within 8 days. No animals showed evidence of downstream calcium alginate
      gel propagation. A minor bioactive response to the alginate gel was noted at 30
      days, and fibrous tissue grew over the aneurysm orifice, sealing off the defect.
      No degenerative or inflammatory response was observed. At 90 days, moderate
      fibrous tissue surrounded the alginate. Tissue growth across the aneurysm neck
      remained complete and stable with no signs of neointimal growth into the parent
      vessel. CONCLUSION: Calcium alginate was an effective endovascular occlusion
      material that filled the aneurysm and provided an effective template for tissue
      growth across the aneurysm neck after 30 days and up to 90 days. Complete filling
      of the aneurysm with calcium alginate ensures stability, biocompatibility, and
      optimal healing for up to 90 days in swine.

PMID- 17538388
TI  - Lack of B7 expression, not human leukocyte antigen expression, facilitates immune
      evasion by human malignant gliomas.
AB  - OBJECTIVE: Lack of human leukocyte antigens and costimulatory molecules have been
      suggested as mechanisms by which human malignant gliomas avoid immune recognition
      and elimination. METHODS: Using quantitative multiparameter flow cytometric
      analysis, tumor cells from patients with glioblastoma multiforme (n = 18) were
      examined ex vivo for the expression of human leukocyte antigen Class I and II
      molecules and the costimulatory molecules B7-1 and B7-2. They were compared with
      reactive astrocytes from peritumoral brain metastases (n = 7), and astrocytes
      removed during nontumor surgery (n = 5). RESULTS: In contrast to the vast
      majority of solid peripheral human tumors, these results demonstrate that
      glioblastoma multiforme frequently express both human leukocyte antigen Class I
      and II molecules. Like most solid peripheral tumors, glioblastoma multiforme
      tumor cells express few or no B7 costimulatory molecules. Functional assays using
      heterogeneous ex vivo tumor preparations or pure populations of ex vivo tumor
      cells and microglia obtained using fluorescence-activated cell sorting indicate
      that CD4+ T-cells are activated by tumor cells only in the presence of exogenous
      B7 costimulation (provided by addition of soluble agonist anti-CD28 monoclonal
      antibody). CONCLUSION: Thus, in contrast to many solid peripheral tumors, failure
      to present tumor antigens is not a likely impediment to immunotherapeutic
      strategies against malignant gliomas. Rather, immunotherapeutic strategies need
      to overcome low levels of B7 costimulation.

PMID- 17538389
TI  - New World cranial deformation practices: historical implications for
      pathophysiology of cognitive impairment in deformational plagiocephaly.
AB  - INTRODUCTION: Throughout history, prehistoric and even some contemporary
      civilizations have practiced various forms of intentional and unintentional
      cranial deformation. Plagiocephaly can be the result of craniosynostosis, infant
      positioning, or other unintentional or intentional deformation. MATERIALS: We
      reviewed the medical and anthropological literature and the anthropological
      collections of Arizona State University and the San Diego Museum of Man for
      evidence of cranial deformation and its possible physiological and cognitive side
      effects. Evidence of cranial shaping was also sought among art or stone work from
      representative cultures. RESULTS: The anthropological record and literature
      attest to the presence of much more severe forms of deformation than that seen as
      a result of contemporary infant positioning. Despite this evidence, there is no
      anthropological evidence as to the possible cognitive effects that such
      deformation may have, although some evidence is reviewed that suggests a possible
      physiological mechanism for the same. CONCLUSION: Because we can only view these
      cultures through the relics of time, any conclusions one might draw from the
      anthropological and historical record regarding the cognitive effects of head
      deformation can only be inferred through generalized observations and are
      tenuous. Nevertheless, there does not seem to be any evidence of negative effect
      on the societies that have practiced even very severe forms of intentional
      cranial deformation (e.g., the Olmec and Maya). On the other hand, the physical
      anthropology and the contemporary developmental literature suggest possible
      mechanisms for such an effect.

PMID- 17538391
TI  - Imaging in dementia with Lewy bodies: a review.
AB  - This review discusses the role of functional and structural imaging in patients
      with suspected dementia with Lewy bodies, with particular emphasis on SPECT and
      PET dopaminergic and cerebral perfusion/metabolic techniques. It is envisaged
      that this information may be useful to nuclear medicine physicians, radiologists,
      psychiatrists, neurologists, geriatricians and physicians.

PMID- 17538392
TI  - 99mTc bone scintigraphy superscans: a review.
AB  - Whole-body bone scintigraphy (bone scan) using a (99m)Tc-labelled pharmaceutical
      is one of the most commonly performed radionuclide examinations. In the normal
      patient, both the osseous components of the skeletal system as well as the
      kidneys and bladder are visualized. A superscan is defined as a bone scan which
      demonstrates markedly increased skeletal radioisotope uptake relative to soft
      tissues, in association with absent or faint genito-urinary tract activity. While
      a superscan is relatively uncommon, its recognition is important, as it is
      associated with a number of important underlying diseases. The purpose of this
      review article is to describe the causes and variable features of a superscan and
      depict patterns which may aid in defining the underlying cause for the scan. In
      addition, we will discuss other investigations that may help further to identify
      the underlying disease in such cases.

PMID- 17538393
TI  - The value of 99mTc-MDP bone scintigraphy in staging primary lymphoma of bone.
AB  - AIM: To assess the value of (99m)Tc-MDP bone scintigraphy in the staging of
      primary bone lymphoma. MATERIALS AND METHODS: Thirteen staging scintigrams of
      patients with biopsy proven primary bone lymphoma were reviewed. The number and
      location of involved sites of disease were documented in each case. RESULTS:
      Seven out of 13 scintigrams (54%) demonstrated a single site of bone involvement.
      Six cases (46%) showed multifocal disease, including clinically silent weight
      bearing sites. CONCLUSIONS: Bone scintigraphy is a valuable tool in the staging
      of primary bone lymphoma. It detects multifocal involvement which alters
      prognosis and possibly treatment. Clinically silent involvement of weight-bearing
      sites may be detected allowing prophylactic treatment if required.

PMID- 17538394
TI  - Comparative evaluation of 99mTc-depreotide and 201Tl chloride single photon
      emission tomography in the characterization of pulmonary lesions.
AB  - PURPOSE: To compare (99m)Tc-depreotide and (201)Tl chloride SPET in the
      characterization of pulmonary lesions. METHODS: Fifty-seven pulmonary lesions
      from 33 patients suspected of malignancy in computed tomography, were assessed by
      (99m)Tc-depreotide and (201)Tl early and delayed SPET imaging. Images were
      visually assessed and the tumour-to-normal (T/N) lung activity ratio for early
      (ER) and delayed (DR) scans and the retention index (RI), were calculated in
      every lesion. A final diagnosis was reached for all lesions, based either on
      histology or prolonged clinical and radiological follow-up. RESULTS: Twenty-three
      lesions were characterized as malignant and 34 benign. In visual analysis, all
      malignant lesions accumulated both tracers resulting in sensitivity and negative
      predictive values of 100%. However, false positive interpretations resulted in a
      specificity of 64.7% and 67.6% for (99m)Tc-depreotide and (201)Tl, respectively.
      ER and DR of both agents and the RI of (99m)Tc-depreotide were significantly
      higher in malignant, compared to benign lesions. In defining thresholds of
      abnormality from ROC analysis, a significant increase in specificity was observed
      for both tracers in both scan phases (91.2% for all), as compared to visual
      analysis (P<0.01). There was no significant difference in the diagnostic
      performance between (99m)Tc-depreotide DR and (201)Tl DR, although the former
      provided the highest T/N ratio. CONCLUSION: This study demonstrates that (99m)Tc
      depreotide and (201)Tl SPET are equally effective and may be useful in the non
      invasive determination of lung malignancy. The specificity of both techniques is
      significantly improved by quantifying radiopharmaceutical accumulation in
      pulmonary lesions.

PMID- 17538395
TI  - MDR1, MRP1 and LRP expression in patients with untreated acute leukaemia:
      correlation with 99mTc-MIBI bone marrow scintigraphy.
AB  - BACKGROUND: Chemotherapy failure linked to multidrug-resistance (MDR) plays an
      important role in many cancer types, including leukaemia. It is believed that
      overexpression of some of membrane or intracellular proteins confers the MDR
      phenotype to cancer cells. (99m)Tc-sestamibi (MIBI) is a transport substrate for
      the Pgp pump. We assessed the bone marrow uptake of (99m)Tc-MIBI and its
      correlation with messenger RNA (mRNA) levels of MDR1, multidrug-resistance
      associated protein-1 (MRP1) and lung resistance protein (LRP) in acute leukaemia.
      METHODS: A total of 26 patients (age range 17-72 years; mean age 51.88+/-2.52
      years) with newly diagnosed acute leukaemia were included in the study. The
      expression of MDR1, MRP1 and LRP on mRNA levels were assessed by quantitative RT
      PCR in the blast cells. The MIBI uptake in the bone marrow was evaluated using a
      quantitative scoring system with determination of the tumour-to-background ratios
      for the bone marrow areas. The correlation between the quantitative RT-PCR
      results and MIBI uptake was analysed by using Spearman's rank correlation
      coefficients with two-tailed test of significance. RESULTS: There was an inverse
      relationship between (99m)Tc-MIBI uptake of bone marrow and both mRNA levels of
      MDR1 and MRP1 (P=0.000, r= -0.733 and P=0.001, r= -0.610, respectively). No
      correlation was found between MIBI uptake and mRNA levels of LRP. CONCLUSION:
      Increased expression of MDR1 and MRP1 correlates with a low accumulation of
      (99m)Tc-MIBI in bone marrow areas in patients with acute leukaemia. (99m)Tc-MIBI
      bone marrow scintigraphy can identify the MDR1 and MRP1 phenotype, but not LRP,
      in patients with acute leukaemia.

PMID- 17538396
TI  - Retro-orbital injection is an effective route for radiopharmaceutical
      administration in mice during small-animal PET studies.
AB  - BACKGROUND AND AIM: Small-animal PET is acquiring importance for pre-clinical
      studies. In rodents, radiotracers are usually administrated via the tail vein.
      This procedure can be very difficult and time-consuming as soft tissue
      extravasations are very frequent and tail scars can prevent repeated injections
      after initial failure. The aim of our study was to compare the retro-orbital (RO)
      versus tail vein intravenous (i.v.) administration of (18)F-FDG and (11)C-choline
      in mice for small-animal PET studies. METHODS: We evaluated four healthy female
      ICR CD1 mice according to the following protocol. Day 1: each animal underwent an
      i.v. injection of 28 MBq of (11)C-choline. PET scan was performed after 10 min
      and 40 min. Day 2: each animal received an RO injection of 28 MBq of (11)C
      choline. A PET scan was performed after 10 min and 40 min. Day 3: each animal
      received an i.v. injection of 28 MBq of (18)F-FDG. A PET scan was performed after
      60 min and 120 min. Day 4: each animal received an RO injection of 28 MBq of
      (18)F-FDG. A PET scan was performed after 60 min and 120 min. Administration and
      image acquisition were performed under gas anaesthesia. For FDG studies the
      animals fasted for 2 h and were kept asleep for 20-30 min after injection, to
      avoid muscular uptake. Images were reconstructed with 2-D OSEM. For each scan
      ROIs were drawn on liver, kidneys, lung, brain, heart brown fat and muscles, and
      the SUV was calculated. We finally compared choline i.v. standard acquisition to
      choline RO standard acquisition; choline i.v. delayed acquisition to choline RO
      delayed acquisition; FDG i.v. standard acquisition to FDG RO standard
      acquisition; FDG i.v. delayed acquisition to FDG RO delayed acquisition. RESULTS:
      The RO injections for both (18)F-FDG and (11)C-choline were comparable to the
      intravenous injection of F-FDG for the standard and delayed acquisitions.
      CONCLUSION: The RO administration in mice represents a technical advantage over
      intravenous administration in being an easier and faster procedure. However, its
      use requires high specific activity while its value in peptides and other
      receptor-specific radiopharmaceuticals needs further assessment.

PMID- 17538397
TI  - Objective and subjective comparison of standard 2-D and fully 3-D reconstructed
      data on a PET/CT system.
AB  - OBJECTIVE: The relative advantage of fully 3-D versus 2-D mode for whole-body
      imaging is currently the focus of considerable expert debate. The nature of 3-D
      PET acquisition for FDG PET/CT theoretically allows a shorter scan time and
      improved efficiency of FDG use than in the standard 2-D acquisition. We therefore
      objectively and subjectively compared standard 2-D and fully 3-D reconstructed
      data for FDG PET/CT on a research PET/CT system. MATERIALS AND METHODS: In a
      total of 36 patients (mean 58.9 years, range 17.3-78.9 years; 21 male, 15 female)
      referred for known or suspected malignancy, FDG PET/CT was performed using a
      research PET/CT system with advanced detector technology with improved
      sensitivity and spatial resolution. After 45 min uptake, a low-dose CT (40 mAs)
      from head to thigh was performed followed by 2-D PET (emission 3 min per field)
      and 3-D PET (emission 1.5 min per field) with both seven slices overlap to cover
      the identical anatomical region. Acquisition time was therefore 50% less (seven
      fields; 21 min vs. 10.5 min). PET data was acquired in a randomized fashion, so
      in 50% of the cases 2-D data was acquired first. CT data was used for attenuation
      correction. 2-D (OSEM) and 3-D PET images were iteratively reconstructed.
      Subjective analysis of 2-D and 3-D images was performed by two readers in a
      blinded, randomized fashion evaluating the following criteria: sharpness of
      organs (liver, chest wall/lung), overall image quality and detectability and
      dignity of each identified lesion. Objective analysis of PET data was
      investigated measuring maximum standard uptake value with lean body mass
      (SUV(max,LBM)) of identified lesions. RESULTS: On average, per patient, the
      SUV(max) was 7.86 (SD 7.79) for 2-D and 6.96 (SD 5.19) for 3-D. On a lesion
      basis, the average SUV(max) was 7.65 (SD 7.79) for 2-D and 6.75 (SD 5.89) for 3
      D. The absolute difference on a paired t-test of SUV 3-D-2-D based on each
      measured lesion was significant with an average of -0.956 (P=0.002) and an
      average of -0.884 on a patient base (P<0.05). With 3-D the SUV(max) decreased by
      an average of 5.2% for each lesion, and an average of 6.0% for each patient.
      Subjective analysis showed fair inter-observer agreement regarding detectability
      (kappa=0.24 for 3-D; 0.36 for 3-D) and dignity (kappa=0.44 for 3-D and 0.4 for 2
      D) of the lesions. There was no significant diagnostic difference between 3-D and
      2-D. Only in one patient, a satellite liver metastasis of a colon cancer was
      missed in 3-D and detected only in 2-D. On average, the overall image quality for
      3-D images was equal (in 24%) or inferior (in 76%) compared to 2-D. CONCLUSION: A
      possible major advantage of 3-D data acquisition is the faster patient throughput
      with a 50% reduction in scan time. The fully 3-D reconstruction technique has
      overcome the technical drawbacks of current 3-D imaging technique. In our limited
      number of patients there was no significant diagnostic difference between 2-D and
      fully 3-D.

PMID- 17538398
TI  - Synthesis and evaluation of radioiodine-labelled CP-118,954 for the in-vivo
      imaging of acetylcholinesterase.
AB  - OBJECTIVES: Alzheimer's disease (AD) is characterized by reduced
      acetylcholinesterase (AChE) activity in the post-mortem tissues of AD patients.
      Therefore, AChE has been an attractive target for the diagnosis of AD. In the
      present study, 5,7-dihydro-3-[2-(1-(phenylmethyl)-4-piperidinyl)ethyl]-6H
      pyrrolo[3,2-f]-1,2-benzisoxazol-6-one (CP-118,954), a potent AChE inhibitor, was
      labelled with radioiodine and evaluated as an AChE imaging agent for SPECT.
      METHODS: Radioiodine-labelled CP-118,954 was prepared from CP-144,885 and
      [(125)I]iodobenzyl bromide, and anti-AChE activities of iodine-substituted CP
      118,954 were measured. Metabolism studies were carried out in samples of blood
      and whole brain of mice injected with 2-[(123)I]iodo-CP-118,954 ((123)I-1).
      Tissue distribution studies were also performed in mice injected with I-1, and
      samples of blood, thyroid, stomach, and brain tissue (cerebellum, striatum and
      cortex) were removed, weighed and counted. RESULTS: Of the ligands, 2-iodo-CP
      118,954 exhibited higher binding affinity for AChE (IC50=24 nM) than the other
      positional isomers. 2-[(125)I]Iodo-CP-118,954 was found to have a lipophilicity
      (log P=2.1) favouring brain permeability and metabolic stability in mouse brain,
      but a marginal target (striatum) to non-target (cerebellum) uptake ratio (1.1) in
      mouse brain. CONCLUSION: This result demonstrates that 2-[(125)I]iodo-CP-118,954
      may be unsuitable for AChE imaging. These findings suggest that radioligands
      suitable for AChE imaging should have not only a specific structure but also a
      sub-nanomolar to low nanomolar IC50.

PMID- 17538399
TI  - Clinical role of 123I-IMP SPECT for the differential diagnosis of ocular
      malignant melanoma: a time-course analysis.
AB  - OBJECTIVE: To evaluate the efficacy of (123)I-IMP single photon emission computed
      tomography (SPECT) for the diagnosis of ocular malignant melanoma (MM). METHODS:
      Thirty-eight patients (18 males, 20 females) clinically suspected of having
      ocular MM were retrospectively examined in this study. The age of patients ranged
      from 8 to 81 years (mean 55.6 years). Twelve patients were finally diagnosed as
      having ocular MM. Orbital SPECT images were taken 15 min, 4 h, 24 h and 48 h
      after intravenous injection of 111-222 MBq (3-6 mCi) (123)I-IMP. (123)I-IMP
      uptake in the orbital tumor was visually evaluated as-(negative),+/-(equivocal),
      or+(positive). The uptake index (UI) and increase ratios (IRs) were calculated.
      RESULTS: For visual evaluation, the accuracy of (123)I-IMP for the diagnosis of
      MM was 73.7% (15 min), 81.6% (4 h), 81.6% (24 h) and 86.8% (48 h). When UI and IR
      were calculated on both the MM and non-MM groups, the UI and IR of the MM group
      were significantly higher than those of the non-MM group (P<0.001). Moreover, the
      highest sensitivity (100%) and accuracy (94.7%) were obtained 48 h after (123)I
      IMP administration when the cut-off value of UI was defined as 1.90. CONCLUSIONS:
      This study shows that (123)I-IMP SPECT is useful for the diagnosis of ocular MM.
      The UI values 48 h after the injection were efficient for the differentiation
      between MM and non-MM lesions.

PMID- 17538400
TI  - Clinical competence in myocardial perfusion scintigraphic stress testing: general
      training guidelines and assessment.
AB  - The suggestion by the National Institute for Clinical Excellence (NICE) to more
      than triple the number of myocardial perfusion scintigraphy (MPS) procedures
      carried out by the NHS each year is a challenge both in terms of numbers of gamma
      cameras available to carry out the scans and qualified staff to supervise stress
      tests. In the past, exercise and pharmacological stress testing have been
      supervised only by doctors but, increasingly, this is taken on by suitably
      trained non-medical professionals such as nurses, radiographers and clinical
      technologists. The expansion of the numbers of non-medical professionals
      qualified to supervise stress testing will be key to meeting NICE's
      recommendations. This paper sets out how potential new stressors should be
      identified, what their training should cover and discusses the standards of
      competence they should meet. It provides guidelines for training non-medical
      stressors to perform a safe and efficient stress test during MPS and advice for
      maintaining competency.

PMID- 17538401
TI  - Guidelines--child's play or a practical minefield?

PMID- 17538414
TI  - Replacing a urostomy drainage pouch.

PMID- 17538420
TI  - Why use erythromycin to manage gastroparesis?

PMID- 17538421
TI  - Documenting your preceptor role.

PMID- 17538422
TI  - Is your older patient depressed?

PMID- 17538432
TI  - Nursing2007 infection control survey report.

PMID- 17538434
TI  - Need help finding a vein?

PMID- 17538435
TI  - Stopping the destruction of acute pancreatitis.

PMID- 17538442
TI  - The farewell party: to life!

PMID- 17538443
TI  - Patient education series. Alzheimer's disease.

PMID- 17538448
TI  - Relieving rebound headaches.

PMID- 17538449
TI  - Luke's last day.

PMID- 17538451
TI  - Acute paraplegia.

PMID- 17538452
TI  - Promoting change is as easy as choosing a different seat.

PMID- 17538454
TI  - Frontline managers lead an innovative improvement model.

PMID- 17538455
TI  - Implementation: a team effort.

PMID- 17538456
TI  - Nursing informatics: the economics of education.

PMID- 17538457
TI  - Preventing wrongful discharge: know your facts.

PMID- 17538458
TI  - Best-practice protocols: get your board on board.
AB  - The Institute for Healthcare Improvement once again challenges practitioners and
      administrators to raise care quality through the 5 Million Lives Campaign, a
      sequel to the 100,000 Lives Campaign. Here, learn recommendations for board-of
      director involvement.

PMID- 17538460
TI  - Handhelds and HIPAA.

PMID- 17538461
TI  - Screening for pain.

PMID- 17538462
TI  - Growing revenue with APNs.

PMID- 17538463
TI  - On guard--and on track--with a maintenance program.

PMID- 17538464
TI  - Infection control: it's in your hands.

PMID- 17538468
TI  - Scoliosis: a case study in an adolescent boy.

PMID- 17538469
TI  - Psychosocial factors affecting hip fracture elder's burden of care in Taiwan.
AB  - OBJECTIVE: The aim of this study was to analyze the factors that affect the
      burden of care for primary caregivers of older people during the transition
      period after discharge from the hospital to home. METHODS: Using convenience
      sampling, 95 older patients who had been hospitalized for a hip fracture and
      their primary caregivers were enrolled. Data pertaining to the burden experienced
      by the caregivers were collected 1 week and 1 month after discharge from the
      hospital. RESULTS: The burden of care was characterized as moderate. Physical
      functioning of the older people improved gradually with time after discharge from
      hospital (F = 164.582, p < .001) and were negatively related to caregiver burden.
      The predictive factors for caregiver burden 1 week after hospital discharge
      included the older people's physical functioning and self-efficacy, which
      together contributed to 15.6% of the total variance in caregiver burden. The
      predictive factors for caregiver burden 1 month after hospital discharge were the
      degree of caregiver burden at 1 week and social support, which together
      contributed to 56.0% of the total variance in caregiver burden. CONCLUSION: A
      health education program should be designed to improve the primary caregiver's
      knowledge of providing care and suggest strategies to increase social support to
      reduce the overall burden of care.

PMID- 17538470
TI  - Update on therapy for osteoporosis.
AB  - Recent advances in understanding skeletal metabolism has expanded the
      pharmacological options for treating osteoporosis in women. The antiresorptive or
      anticatabolic drugs are the oldest class known for their positive benefits in
      therapy. A better appreciation of their mode of action reveals much broader
      effects than formerly realized. It provides an entree into understanding the
      actions of drugs on the qualitative elements of bone in addition to the
      quantitative ones on density. New bisphosphonates make for better patient
      adherence to therapy, a continuing problem in long-term care. A new class of
      drugs called anabolic agents, typified by teriparatide usher, has the potential
      to reconstitute destroyed bone and bring it to its pristine state. This article
      briefly focuses on where we were in this arena a mere decade ago and then
      highlights the new elements in therapy and physiology of the skeleton. A brief
      expose on osteoporosis in men is also provided.

PMID- 17538472
TI  - A randomized trial to evaluate compliance in terms of patient comfort and
      satisfaction of two pneumatic compression devices.
AB  - PURPOSE: Venous thromboembolism (VTE) incidence can be substantially reduced with
      prophylaxis, which includes pneumatic compression device (PCD) use. METHODS: To
      determine whether patient comfort and satisfaction correlated to compliance in
      wearing PCDs, patients were randomly assigned to either of two effective calf
      high PCDs. Education and handouts were provided to both groups. Patients were
      given a survey rating their comfort, satisfaction, and compliance. At the
      conclusion of the study, healthcare providers completed a questionnaire comparing
      both PCDs. RESULTS: A total of 65 patients participated. The main significant
      differences between groups were seen in the patient perceptions questionnaire for
      two items: "the device was hot" (p = .014) and "device made my legs sweat" (p =
      .029). The PCD that provided more comfort and satisfaction was worn for a greater
      amount of time, 85% vs. 81%, respectively. CONCLUSIONS: Results suggest that
      patients are more compliant with a PCD that promotes patient comfort when worn.

PMID- 17538473
TI  - Pathogenesis of tendon rupture secondary to fluoroquinolone therapy.
AB  - Tendon rupture related to trauma and corticosteroid injection, in and about
      tendon insertion sites, is well documented in the literature. Rupture of tendon
      after fluoroquinolone therapy has been identified in the recent past. Both short-
      and long-term courses of antibiotic treatment with fluoroquinolone may
      precipitate alteration in tendon matrix leading to tendinopathy with subsequent
      rupture. The pathogenesis of tendon rupture secondary to fluoroquinolone therapy
      is presented.

PMID- 17538475
TI  - Personal health record: new opportunity for patient education.
AB  - The personal health record (PHR) allows individuals to keep track of their health
      care information in one location. Maintaining a PHR encourages increased personal
      participation in healthcare and fosters a greater emphasis on communication
      between the individual and the caregivers. The creation of a PHR provides the
      opportunity for health professionals to educate patients about personal health
      matters and presents a tool for enhancing health literacy. As patients become
      more adept at communicating with their caregivers and recording important health
      information, the ability to participate in decision making is enhanced.
      Assessment of health literacy and functional ability allows the PHR to be adapted
      to accommodate the needs of the individual. Identification of family members or
      other significant individuals early on is essential, and education efforts should
      begin promptly. This article provides information on the benefits of a PHR.
      Considerations for health literacy and ability to maintain a PHR are discussed,
      and examples of using a transdisciplinary approach to development and
      implementation of a PHR are examined. With proper design and education, the PHR
      allows individuals to participate more fully in their own healthcare.

PMID- 17538477
TI  - Medicating young or very young patients--part II.
AB  - Having a sick child can be stressful for parents, even if the illness is a mild
      cold or gastrointestinal upset. Part of that stress may be related to uncertainty
      about when to seek professional help and when to choose an over-the-counter (OTC)
      medication. When choosing to use an OTC medication, parents are faced with
      another uncertainty-which agent to use. The variety of available agents, many
      with pictures of children on the labels or names that indicate "for children"
      makes a wise choice challenging. Knowledgeable nurses, who interact with sick
      children and their parents in any setting, can do much to relieve some of this
      uncertainty and stress by talking to parents about the treatment and medication
      choices they make. In the following discussion, examples of medications used to
      treat common problems in younger patients are discussed. Contraindications,
      safety concerns, potential drug-drug interactions, and safe administration
      guidelines are identified for each example. Part III of this series will address
      examples of medications used to treat more complicated childhood problems, such
      as asthma, allergy, attention-deficit disorders, and obesity.

PMID- 17538485
TI  - A practical approach to the ultrasound characterization of adnexal masses.
AB  - Because pelvic ultrasound is commonly used to evaluate adnexal masses, it is
      important to understand the most useful sonographic features for predicting
      benign and malignant masses. Determining whether an adnexal mass is of ovarian or
      extraovarian origin is key in arriving at the most likely diagnosis. Most adnexal
      masses are benign, and each of the most common benign ovarian lesions has a
      typical sonographic appearance. Additionally, most malignant ovarian neoplasms
      have a solid component with detectable flow by Doppler ultrasound, allowing one
      to strongly suggest the diagnosis. We will review an approach to the ultrasound
      diagnosis of adnexal masses that progresses through a series of 4 questions to
      help lead one to the most likely diagnosis.

PMID- 17538486
TI  - Nuchal translucency and first trimester risk assessment: a systematic review.
AB  - First-trimester risk assessment for fetal aneuploidy using nuchal translucency
      (NT) measurement is rapidly gaining popularity in the United States. In
      combination with maternal serum markers in the first trimester, the screening
      performance is exceptionally good, with detection rates of more than 80% at a
      screen positive rate of 5%. Recently, the method has been validated for screening
      for Down syndrome and other aneuploidies in multicenter trials in the United
      States and elsewhere. Compliance with established criteria for measurement of the
      NT is essential to achieve uniform reliability and high screening test
      sensitivity. There is an international consensus about the importance of specific
      training in the NT examination, conformity to standards of NT measurement, and
      regular audit for quality assurance. In the United States, the Nuchal
      Translucency Quality Review program has been developed to administer
      credentialing and quality review for registered practitioners. The Nuchal
      Translucency Quality Review credentials signify the proficiency of the
      sonographer or sonologist in NT measurement and participation in a regular
      quality assurance audit. We encourage accreditation of clinical sites offering
      first-trimester risk assessment to ensure the highest quality care.

PMID- 17538487
TI  - The value of single umbilical artery in the prediction of fetal aneuploidy:
      findings in 12,672 pregnant women.
AB  - OBJECTIVES: To assess the risk of the association of single umbilical artery and
      aneuploidies. METHODS: In a general unselected obstetric population of 12,672
      singleton pregnant women from January 1998 to December 2002, we detected 61
      fetuses (prevalence, 0.48%) with single umbilical artery (SUA) on prenatal
      ultrasound at 16 to 23 menstrual weeks. RESULTS: Among the 61 fetuses with 2
      vessel cord, 39 (64%) had SUA as an isolated finding, and 22 (36%) had additional
      findings, either minor or major. One (2.56%) of the 39 fetuses with SUA as an
      isolated finding had aneuploidy (trisomy 21 at maternal age of 32 years), whereas
      5 (41.6%) of the 12 fetuses with SUA concomitant with major anomalies were
      aneuploid. None of the 10 fetuses with SUA and minor anomalies had aneuploidy.
      Among the 12,611 women with 3-vessel cord, we instead found 8 cases of trisomy 21
      (0.06%), 1 case of translocation 14-21 (0.007%), 5 cases of trisomy 18 (0.04%), 1
      case of trisomy 13 (0.007%), 1 case of 47,XXX (0.007%), and 2 cases of monosomy X
      (0.01%). CONCLUSIONS: In an unselected population, second trimester sonographic
      detection of SUA and major fetal anomalies indicate increased risk for fetal
      aneuploidy. However, even if this study is based on a large population, the only
      1 case of trisomy 21 among the fetuses with SUA as an isolated finding is not
      sufficient to draw a conclusion, and larger studies are needed to confirm or
      infirm this single case.

PMID- 17538488
TI  - The role of sonography in imaging of the biliary tract.
AB  - Sonography is the recommended initial imaging test in the evaluation of patients
      presenting with right upper quadrant pain or jaundice. Dependent upon clinical
      circumstances, the differential diagnosis includes choledocholithiasis, biliary
      stricture, or tumor. Sonography is very sensitive in detection of mechanical
      biliary obstruction and stone disease, although less sensitive for detection of
      obstructing tumors, including pancreatic carcinoma and cholangiocarcinoma. In
      patients with sonographically documented cholelithiasis and choledocholithiasis,
      laparoscopic cholecystectomy with operative clearance of the biliary stone
      disease is usually performed. In patients with clinically suspected biliary stone
      disease, without initial sonographic documentation of choledocholithiasis,
      endoscopic ultrasound or magnetic resonance cholangiopancreatography is the next
      logical imaging step. Endoscopic ultrasound documentation of choledocholithiasis
      in a postcholecystectomy patient should lead to retrograde cholangiography,
      sphincterotomy, and clearance of the ductal calculi by endoscopic catheter
      techniques. In patients with clinical and sonographic findings suggestive of
      malignant biliary obstruction, a multipass contrast-enhanced computed tomography
      (CT) examination to detect and stage possible pancreatic carcinoma,
      cholangiocarcinoma, or periductal neoplasm is usually recommended. Assessment of
      tumor resectability and staging can be performed by CT or a combination of CT and
      endoscopic ultrasound, the latter often combined with fine needle aspiration
      biopsy of suspected periductal tumor. In patients whose CT scan suggests hepatic
      hilar or central intrahepatic biliary tumor, percutaneous cholangiography and
      transhepatic biliary stent placement is usually followed by brushing or
      fluoroscopically directed fine needle aspiration biopsy for tissue diagnosis.
      Sonography is the imaging procedure of choice for biliary tract intervention,
      including cholecystostomy, guidance for percutaneous transhepatic
      cholangiography, and drainage of peribiliary abscesses.

PMID- 17538489
TI  - The role of ultrasound in the diagnosis and treatment of chronic venous
      insufficiency.
AB  - Chronic venous insufficiency (CVI) is an exceedingly common and underdiagnosed
      disorder with a wide range of symptoms and prognosis ranging from cosmetic issues
      to skin ulceration with tissue loss. Ultrasound plays a pivotal role in the
      diagnosis, classification, and guidance of percutaneous treatment of CVI. It is
      therefore of critical importance to the practicing radiologist to have a sound
      understanding of the pathophysiology, pertinent venous anatomy, and
      classification of CVI. We review the superficial and deep venous anatomy of the
      lower extremity, introduce a pattern recognition approach for mapping of
      varicosities, and review the protocol for ultrasound evaluation for CVI. In
      addition, we discuss the pathophysiology of CVI and the role of ultrasound in
      guidance for and follow-up of percutaneous treatment.

PMID- 17538509
TI  - Sonographic physical diagnosis 101: teaching senior medical students basic
      ultrasound scanning skills using a compact ultrasound system.
AB  - This project was designed to test the feasibility of introducing ultrasound to
      senior medical students as a primary diagnostic tool in the evaluation of
      patients. Specifically, its aim was to determine if it is possible for medical
      students untrained in sonography to gain basic competence in performing abdominal
      ultrasound with limited didactic and hands-on instructions. Registered
      sonographers provided the students with hands-on instructions on the use of a
      compact ultrasound system. They were likewise shown how to evaluate specific
      organs and perform measurements. The results of the student measurements and
      those obtained by the sonographers were compared. There was close correlation
      between the results obtained by sonographers and students on both normal and
      abnormal findings. This supports the concept that medical students can be taught
      basic ultrasound skills with limited didactic and hands-on instructions with the
      potential of using these skills in the patient clinics as an adjunct to routine
      physical diagnosis.

PMID- 17538512
TI  - Chilliness: a vasomotor symptom in Japan.
AB  - OBJECTIVE: To examine the differences between biomedical and Japanese women's
      concepts of vasomotor symptoms and the relationships between the symptom of
      chilliness (hiesho) and menopause status, other vasomotor symptoms, and
      environmental factors such as soy isoflavone intake and exposure in Japan.
      DESIGN: Participants were healthy Japanese women, aged 45 to 55, living in Kyoto
      and Fukushima prefectures, divided into menopausal groups based on menstrual
      patterns. Women recalled 82 general health symptoms during the previous 2 weeks
      and collected finger-prick dried blood spots and matched 24-hour dietary records,
      which were analyzed, respectively, for isoflavone concentration by high
      performance liquid chromatography coulometric electrode array detection and for
      soy isoflavone intake using a Japanese phytochemical database. RESULTS: An
      examination of konenki (Japanese for climacteric) symptoms suggests that
      chilliness (hiesho), which was reported by 29.3% of participants compared with a
      range of 3.0% to 22.1% for hot flushes, constitutes an important vasomotor
      symptom. Chilliness prevalence differed significantly between premenopausal and
      other menopausal status groups, with positive correlations with other estrogen
      influenced sexual-vasomotor symptoms and negative correlations with isoflavone
      concentrations. Negative correlations with soy isoflavone intake were also found
      for sweating, although not for nobose and hoteri (two Japanese terms for hot
      flush). CONCLUSIONS: Chilliness seems to be a more important vasomotor symptom
      than hot flushes and sweats in Japanese women and may reflect differing
      thermoregulatory physiology, possibly influenced by dietary soy.

PMID- 17538513
TI  - Famciclovir reduces viral mucosal shedding in HSV-seropositive persons.
AB  - OBJECTIVE: Many cases of herpes simplex virus (HSV) infection occur through
      asymptomatic shedding from persons without evidence of clinical disease. This
      study explores whether famciclovir reduces HSV shedding in HSV-2 seropositive
      persons with or without a history of symptomatic genital herpes. STUDY DESIGN:
      One hundred twenty-seven HSV-2 seropositive participants were randomly assigned
      to 42 days of famciclovir, followed by 14 days of washout and 42 days of placebo,
      or vice versa. All subjects swabbed the genital/perianal area; those with HSV-1
      infection also swabbed the oral area daily for HSV DNA PCR. RESULTS: Famciclovir
      reduced genital and oral HSV shedding from 11.4% of days during the placebo
      period to 4.7% of days during famciclovir therapy. The reduction was greater in
      participants with a history of genital herpes (74%) than in those without such a
      history (30%). In multivariate analyses, famciclovir protected against total
      (clinical and subclinical) genital shedding among persons with a clinical history
      of genital herpes (RR, 0.23; 95% CI, 0.15-0.35; P < 0.001). Among HSV-2
      seropositive participants without a history of genital herpes, 60% had HSV
      detected in the genital area at least once during the study. Famciclovir therapy
      did not result in a statistically significant reduction in total HSV shedding in
      participants without a history of genital herpes. CONCLUSION: Famciclovir therapy
      decreases genital HSV shedding in HSV-seropositive persons, especially those with
      a history of genital herpes. Overall, antiviral drugs may have varying effects on
      symptomatic and asymptomatic viral shedding, depending on the clinical history of
      the disease.

PMID- 17538514
TI  - Population-based outreach for Chlamydia screening in men: results from a
      randomized trial.
AB  - OBJECTIVE: To evaluate the feasibility and efficacy of population-based outreach
      strategies to improve genital Chlamydia trachomatis (CT) screening in men. STUDY
      DESIGN: In a randomized trial, male enrollees ages 21-25 (n = 8820) were selected
      from the automated files of Group Health Cooperative and randomized to: a letter
      + test-request card for a CT urine home sampling kit (arm 1, n = 2940); a letter
      + mail-back sampling kit (arm 2, n = 2940); or a usual care control (arm 3, n =
      2940). One reminder was sent to arms 1 and 2. The outcome was CT testing rates in
      the 4 months postrandomization. RESULTS: 105 of 2940 (3.6%) men in arm 1 and 230
      of 2940 (7.8%) in arm 2 returned mailed specimens. All 335 respondents were
      sexually experienced, 43% had >2 sex partners in the past year, and 80% reported
      no genitourinary symptoms. Compared to arm 3, the relative risk of being tested
      was 5.6 (95% confidence interval (CI) 3.6-8.7) for arm 1 and 11.1 (95% CI 7.3
      16.9) for arm 2. Arm 2 was significantly more likely to be tested than arm 1. CT
      prevalence for mailed-back specimens was 1.0% (1 of 105) for arm 1 and 2.6% (6 of
      230) for arm 2; 70% of all positive intervention tests were from mailed samples.
      CONCLUSIONS: Both strategies resulted in significantly higher CT testing than
      usual care, but the intervention response rate was low (5.7% overall). Direct kit
      mailing performed best. In US populations, the value of mailed outreach
      strategies to men must be considered in the context of other CT screening
      priorities.

PMID- 17538515
TI  - Heterosexual behavior patterns and the spread of HIV/AIDS: the interacting
      effects of rate of partner change and sexual mixing.
AB  - OBJECTIVES: This study evaluates whether the influence of sexual mixing patterns
      on the human immunodeficiency virus (HIV) epidemic curve is sensitive to the
      prevailing rates of sexual partner change in a population. STUDY DESIGN: A
      biobehavioral macrosimulation model is employed to assess the interacting
      dynamics of the rates of sexual partner change and patterns of sexual mixing
      between population subgroups. HIV spread is simulated under 2 rates of partner
      change scenarios and under various degrees of assortativeness in sexual mixing
      patterns. RESULTS: With high rates of partner change, disassortativeness in
      sexual mixing tends to increase the overall size of the HIV epidemic. However,
      when relatively low rates of partner change are simulated, disassortative mixing
      yields a smaller epidemic. This pattern is further influenced by the underlying
      sexual transmission probabilities of HIV. CONCLUSIONS: Each of the various
      determinants of the sexual spread of HIV must not be considered in isolation.
      Instead, the interactive nature of those determinants should be accounted for in
      discussions of HIV epidemic dynamics.

PMID- 17538516
TI  - Within the hidden epidemic: sexually transmitted diseases and HIV/AIDS among
      American Indians and Alaska Natives.
AB  - OBJECTIVES: To review the epidemiology, research, and prevention programs for
      sexually transmitted diseases in American Indians and Alaska Natives (AI/ANs).
      STUDY DESIGN: We reviewed the current national and regional trends in sexually
      transmitted diseases (STDs) for AI/ANs from 1998-2004, peer-reviewed studies from
      January 1996, through May 2006, and reports, unpublished documents, and
      electronic resources addressing AI/AN STD prevention and control. RESULTS: STD
      prevalence among AI/ANs remains high. For example, the case rate of C.
      trachomatis in the North Central Plains AI/AN populations is 6 times the overall
      US rate. Trends for C. trachomatis also show sustained increases. Little research
      exists on STDs for this population, and most is focused on HIV/AIDS. Fear of
      compromised confidentiality, cultural taboos, and complex financial and service
      relationships inhibit effective surveillance, prevention, and management.
      CONCLUSIONS: Recommendations for STD control in this population include improved
      local surveillance and incorporation of existing frameworks of health and healing
      into prevention and intervention efforts. Research defining the parameters of
      cultural context and social epidemiology of STDs is necessary.

PMID- 17538517
TI  - Walking index for spinal cord injury.
AB  - This review reports on the contemporary possibilities of objective evaluation of
      walking ability in patients with paraplegia following a spinal cord injury.
      Current methods of evaluation of walking function, i.e. the ASIA Classification,
      Functional Independence Measure (FIM), Barthel Index and Spinal Cord Independence
      Measure (SCIM) are described. The latest classification, known as the WISCI
      (Walking Index for Spinal Cord Injury) is described in detail. WISCI is the most
      detailed scale that is also the most sensitive to changes in the patient's
      walking ability compared to the other scales.

PMID- 17538519
TI  - Evaluation of treatment results of patients with Dupuytren's contracture--our
      clinical experience.
AB  - Dupuytren's contracture is a common condition leading to impairment of the
      function of the hand which affects from 2 to 12 % of the population, mainly
      males, and presents as progressive contracture of fingers caused by shortening of
      the palmar aponeurosis. The objective of the work was to present our own approach
      to managing Dupuytren's disease and evaluate treatment results in patients with
      hypertrophy of the palmar aponeurosis. Material and method 288 patients with
      Dupuytren's disease were treated at the Plastic Surgery Hospital in Polanica
      Zdroj over a period of 25 years (1977-2002). The present paper is a retrospective
      analysis of treatment results in 253 patients for whom complete medical
      documentation was available. All patients were operated in local anaesthesia in
      ischemia. A Bunnell flap skin incision was followed by a fasciectomy of the
      hypertrophied segment of the palmar aponeurosis. The skin wound was closed using
      V-Y plasty. Postoperative management involved hand elevation and early
      rehabilitation. Results Restoration of the full range of motion and total
      extension in the MP joint and the interphalangeal joints were achieved in 70% and
      68% of patients, respectively. Of 145 patients who were professionally active,
      132 were able to return to work. Finger amputation was necessary in 2 patients,
      one patient suffered from arthrodesis and two other developed skin necrosis which
      was removed with the wound closed by skin grafts. A follow-up examination 6
      months after the operation revealed a recurrence in 8 patients and deterioration
      of hand dexterity with finger stiffness in 4. Conclusions A low complication rate
      and good treatment results are arguments in favour of the approach adopted at our
      hospital, i.e. surgery in local anaesthesia in ischemia with compressive
      bandaging, using a Bunnell flap skin incision followed by radical fasciectomy and
      V-Y plasty.

PMID- 17538520
TI  - Short-term clinical experience with hip resurfacing arthroplasty.
AB  - BACKGROUND: This paper discusses the authors' experience with hip resurfacing
      arthroplasty. Although introduced many years ago, the method did not gain wide
      popularity because of poor long-term outcomes. At present, owing to the
      introduction of metal-on-metal bearings and hybrid fixation techniques, short-
      and mid-term results are very good and encourage wider use of this technique,
      especially in the younger and more active patients whose results with standard
      total hip replacements would be unsatisfactory. MATERIAL AND METHODS: We
      performed 13 hip resurfacing arthroplasties at our institution between August 1,
      2005, and May 1, 2006. Twelve patients reported for the scheduled follow-up and
      were included in the study. Treatment outcomes were assessed according to the
      Harris Hip Score. RESULTS: The short-term outcomes of hip resurfacing
      arthroplasties are encouraging. In the study group there were no intraoperative
      complications, infections, peripheral nerve palsy, hip dislocations or clinically
      overt vein thrombosis. All of the patients reported complete or major pain
      relief. Clinical assessment according to the Harris Hip Score revealed
      improvement from an average of 57.7 (20.1) points preoperatively to an average of
      87.7 (12) points after the surgery. Crutches were used for a maximum of 6 weeks
      postoperatively. All of the patients are currently able to walk without crutches
      with full weight-bearing. CONCLUSIONS: 1) Hip resurfacing arthroplasty seems to
      be an advisable method of operative management of younger, active patients, in
      whom standard THR would be associated with a high risk of failure; it allows THR
      to be postponed and carried out as a revision surgery with the acetabular
      component already in place. 2) Despite the good short- and mid-term results, the
      utility of this method should be evaluated with caution due to the lack of
      adequate long-term follow-up data.

PMID- 17538521
TI  - Diagnostic value of serum chromogranin-A combined with MIBG scintigraphy
      inpatients with adrenal incidentalomas.
AB  - AIM: Adrenal incidentalomas (AI) are defined as asymptomatic adrenal masses
      occasionally discovered during high-resolution imaging procedures, as computed
      tomography or magnetic resonance. Pheochromocytoma, a chromaffin tumour, must be
      excluded before any invasive diagnostic or therapeutic procedure, in order to
      avoid dangerous acute catecholamines-release into blood stream. Chromogranin-A
      (CgA) is a member of the granin family contained in secretory vesicles of
      chromaffin system. This study investigated the performance of serum CgA in
      detecting or excluding pheochromocytoma among patients with AI. METHODS: We
      enrolled 348 patients by AI > 20 mm without clinical or biochemical signs for
      corticosteroids overproduction. Serum CgA was assayed by a specific
      immunoradiometric method and a [123I] metaiodobenzylguanidine (MIBG) scan was
      performed in the 39 CgA-positive patients. RESULTS: Eighteen out of these
      patients showed a positive scan and were submitted to laparoscopic adrenalectomy.
      Pheochromocytoma was histologically confirmed in all cases . The patients with
      positive serum CgA, were reassessed 1 year later by clinical examination and
      serum CgA assay. None of patients developed clinical symptoms of chromaffin
      tissue hyperactivity , nor showed a serum CgA increase. Serum levels of CgA were
      significantly higher inpatients with pheochromocytoma than inpatients without
      (P<0.0001). CONCLUSION: We concluded that serum CgA assay is effective as a
      single marker to detect or exclude sporadic pheochromocytoma among patients with
      AI > 20mm. Particularly, a negative serum CgA assay may be used to rule out
      [123I] MIBG imaging and /or other diagnostic procedures.

PMID- 17538522
TI  - Fluorodeoxyglucose PET/CT in patients with differentiated thyroid cancer and
      elevated thyroglobulin after total thyroidectomy and (131)I ablation.
AB  - AIM: The aim of this study was to evaluate the role of 18F fluorodeoxyglucose
      positron emission tomography (FDG-PET), differentiated thyroid carcinoma (DTC)
      treated with therapeutic (131)I because of elevated thyroglobulin (Tg) levels
      during follow up. The results of FDG-PET/CT were compared with post-therapy
      (131)I whole body scan (131I-t-WBS) and Tg at short term follow up. METHODS:
      Forty-five patients with DTC underwent a new therapeutic (131I) administration
      based upon Tg values >1.5 ng/mL. All patients underwent (131I-t-WBS) 5-7 days
      after 131I therapy. A few days before 131I administration, a FDG-PET scan was
      performed in all patients. FDG-PET/CT was considered positive (PET+) when at
      least one abnormal focus of FDG uptake was found; likewise, 131I-t-WBS was
      considered positive(WBS+) when at least on abnormal focus of uptake was found.
      Assessment of short-term response to radioiodine was performed by measuring Tg
      values. RESULTS: FDG-PET/CT was positive in 32 patients, 23 of which had positive
      131I-t-WBS and negative in 13, 8 of which had a negative 131I-t-WBS. Overall
      agreement was 69%. Tg values were significantly higher in FDG-PET/CT positive
      (502+/-1 027 ng/mL) than in FDG-PET/CT negative patients (57+/-94 ng/mL). A
      significant difference emerged between 131I-t-WBS positive (561 +/- 1 086 ng/mL)
      and 131I-t-WBS negative (65+/- 120 ng/mL) findings. In these 45 patients Tg
      normalized in 36%, was reduced by at least 50% in 24% and remained unchanged in
      the remaining 40%. Overall, at short-term follow-up, Tg values normalized in 77%
      of the 13 patients with negative FDG-PET/CT and in 19% of the 32 patients with
      positive FDG-PET/CT. CONCLUSION: FDG-PET/CT is a powerful and useful tool for
      assessing patients with DTC. it can provide additional information in those
      patients with high Tg at follow-up and eligible for 131I therapy. A negative FDG
      PET/CT could also represent a prognostic tool combined with serum Tg testing a
      short term follow-up.

PMID- 17538523
TI  - S-factor calculations for mouse models using Monte-Carlo simulations.
AB  - AIM: Targeted radionuclide therapy applications require the use of small animals
      for preclinical experiments. Accurate dose estimation is needed in such animals
      to explore and analyze the toxicity of injected radiopharmaceuticals. We
      developed two numerical models to allow for a more accurate mouse dosimetry.
      METHODS: A frozen nude mouse (30 g) was sliced and digital photographs were taken
      during the operation. More than 30 organs and tissues were identified and
      manually segmented. A digital (voxel-based) and a mathematical model were
      constructed from the segmented images. Important organs were simulated as
      radiation sources using the Monte-Carlo code MCNP4C. Mono-energetic photons from
      0.005 to 2 MeV, and monoenergetic electrons from 0.1 to 2.5 MeV were simulated.
      Activity was supposed to be uniform in all source organs. RESULTS: Results from
      monoenergetic emissions were integrated over emission spectra. Radionuclide S
      factors (Gy/Bq.s) were calculated by taking into account both electron and photon
      contributions. A comparison of the results obtained with either a voxel-based or
      mathematical model was carried out. The voxel-based model was then used to revise
      dosimetric results, obtained previously under the assumption that all emitted
      energy was absorbed locally. For (188)Re, the self-absorbed doses in xenografted
      tumors were 39-69% lower than that obtained by assuming local energy deposition.
      CONCLUSION: The voxel-based models represent more realistic anatomic approach.
      The rapid advancement of computer science and new features added to Monte-Carlo
      codes permit considerable reduction of computational run time. Cross-doses should
      not be neglected when medium to high energy beta emitters are being used for
      preclinical experiments on mice.

PMID- 17538524
TI  - Anatomic and functional imaging in the management of lymphoma.
AB  - Lymphoma has become one of the most successfully treated malignancies. The
      success of treatment and long-term prognosis depend on accurate staging in which
      imaging plays a pivotal role. In addition to staging, imaging assists in the
      evaluation of early and late response to therapy, detecting disease activity in a
      residual mass and locating sites of recurrence. The mainstay of imaging remains
      computed tomography (CT), which has replaced lymphangiography, and staging
      laparotomy. Magnetic resonance imaging (MRI) has additional value in detecting
      disease in bone marrow, the musculoskeletal and central nervous system. Recent
      technical developments in CT and MRI have improved acquisition times and
      resolution, but the main drawback of cross-sectional imaging techniques is their
      reliance on size criteria to define disease, with consequent failure to detect
      disease in small lymph nodes and exclude disease in large, but treated, masses.
      Diffuse visceral involvement is likewise difficult to detect by both modalities.
      Functional imaging with nuclear medicine techniques offers an answer to these
      problems. Imaging with the fluorinated glucose analogue, [18F]FDG positron
      emission tomography (PET), can detect metabolically active disease by its
      increased glycolysis that is proportional to mitotic activity. It can separate
      high from low-grade tumors and aid in prognostication. Recent publications
      suggest that imaging with [18F]FDG PET should be an important component in
      staging; assessment of response to therapy and restaging. Like other imaging
      modalities, it has its own drawbacks including inability to detect very small
      lesions (<5 mm) and reduced specificity due to increased uptake in metabolically
      active inflammatory and infective tissues. The new generation of hybrid PET-CT
      combines anatomical and functional imaging and is considered the state-of-the-art
      imaging technique for the assessment of lymphoma and other malignancies.

PMID- 17538525
TI  - Cost-effectiveness analysis in the clinical management of patients with known or
      suspected lung cancer: [18F]fluorodeoxyglucose PET and CT comparison.
AB  - AIM: The aim of this study was to evaluate the economic impact of the
      introduction of positron emission tomography (PET) in the clinical management of
      patients with known or suspected lung cancer through a cost-effectiveness
      analysis of different diagnostic strategies. METHODS: In Italy, 75 patients with
      known or suspected lung cancer were included in the study. Three different
      diagnostic strategies were compared: 1) baseline or traditional strategy, i.e.
      computed tomography (CT) alone; 2) strategy A, i.e. PET for indefinite CT; 3)
      strategy B, i.e. PET for all. For each strategy expected costs and life
      expectancy, as measured by life year saved (LYS), were evaluated. Incremental
      cost-effectiveness ratio (ICER) was calculated to identify the most effective
      strategy. RESULTS: Compared to the baseline strategy, the introduction of PET
      changed the clinical management in 40% of cases in strategy A and in 51% of cases
      in strategy B, with an optimization of the clinical management. Costs of strategy
      A (2735.42 Euro) and strategy B (2984.52 Euro) were, respectively, 8% and 18%
      higher than the baseline strategy (2534.81 Euro). LYS was 2.04 and 2.64 for
      strategy A and B, which were, respectively, 4% and 35% higher than the baseline
      strategy (1.96 LYS). The ICERs were 2507.63 Euro/LYS and 415.17 Euro/LYS for
      strategy A and B, respectively. Strategy A is dominated by strategy B, which is
      more expensive, but also more effective. CONCLUSION: In Italy, the introduction
      of PET in the clinical management of all patients with known or suspected lung
      cancer previously evaluated with CT is cost-effective and allows to gain 2.64
      life years at an annual cost of about 415 Euro.

PMID- 17538526
TI  - Multistate outbreak of Salmonella serotype Tennessee infections associated with
      peanut butter--United States, 2006-2007.
AB  - In November 2006, public health officials at CDC and state health departments
      detected a substantial increase in the reported incidence of isolates of
      Salmonella serotype Tennessee. In a multistate case-control study conducted
      during February 5-13, 2007, illness was strongly associated with consumption of
      either of two brands (Peter Pan or Great Value) of peanut butter produced at the
      same plant. Based on these findings, the plant ceased production and recalled
      both products on February 14, 2007. The outbreak strain of Salmonella Tennessee
      subsequently was isolated from several opened and unopened jars of Peter Pan and
      Great Value peanut butter and from two environmental samples obtained from the
      plant. New case reports decreased substantially after the product recall. As of
      May 22, 2007, a total of 628 persons infected with an outbreak strain of
      Salmonella serotype Tennessee had been reported from 47 states since August 1,
      2006. Local and state public health officials in multiple states, with assistance
      from CDC and the Food and Drug Administration (FDA), are continuing to
      investigate this outbreak caused by peanut butter, a new food source for
      salmonellosis in the United States. All remaining jars of Peter Pan or Great
      Value peanut butter with a product code beginning with 2111 should be discarded.

PMID- 17538527
TI  - Sunburn prevalence among adults--United States, 1999, 2003, and 2004.
AB  - Episodic acute overexposure to ultraviolet (UV) radiation (i.e., sunburn) is an
      important risk factor for two types of skin cancer: basal cell carcinoma and
      melanoma. Melanoma is the most lethal type of skin cancer. In 2003, a total of
      45,625 new cases of melanoma were diagnosed in the United States, and 7,818
      persons died from the disease. A meta-analysis of 57 studies indicated that the
      relative risk for melanoma among persons with sunburn history compared with those
      without sunburn history was 2.03 (95% confidence interval [CI] = 1.73-2.37).
      Monitoring sunburn prevalence with population-based surveys allows an estimate of
      compliance with sun-protection behaviors, assessments of risk for developing skin
      cancer, and measurement of the success of prevention programs. To evaluate trends
      in sunburn prevalence among U.S. adults, CDC analyzed cross-sectional data from
      the 1999, 2003, and 2004 Behavioral Risk Factor Surveillance System (BRFSS)
      surveys. This report describes the results of that analysis, which indicated that
      sunburn prevalence among all adults increased from 31.8% in 1999 to 33.7% in
      2004. Further research is needed to determine which interventions will best
      improve sun-protection behaviors among the public.

PMID- 17538528
TI  - Characteristics and health of caregivers and care recipients--North Carolina,
      2005.
AB  - Approximately 53.4 million caregivers in the United States provide an estimated
      $257-$389 billion worth of unpaid care annually to persons of all ages with
      disabilities and chronic illness. The health of caregivers and their ability to
      continue their contributions have emerged as public health concerns. A 2004 study
      indicated that those persons who provided the most intense caregiving reported
      substantially poorer health than noncaregivers or those with modest caregiving
      responsibilities. A Healthy People 2010 objective calls for public health
      surveillance and health promotion programs for persons with disabilities and
      caregivers in every state and the District of Columbia (objective 6-13). Although
      limited caregiver surveys have provided data at the national level, data have not
      been available at the state level to characterize the health of caregivers or
      health effects of caregiving. Such information could be useful to states for
      planning and policy decisions and the development and implementation of
      interventions to promote caregivers' health. To analyze the characteristics and
      health of caregivers and care recipients and to assess the effects of caregiving,
      data were analyzed from a caregiver module that was piloted in North Carolina in
      the 2005 Behavioral Risk Factor Surveillance System (BRFSS) survey. This report
      summarizes the results of that analysis, which determined that caregivers
      provided an average of 20.1 hours of care per week, and 72.2% of caregivers lived
      in the same household as (24.9%) or within 20 minutes of (47.3%) the care
      recipient. Caregivers were more likely to be women (59.5%) than men and averaged
      more days when their mental health was not good when compared with noncaregivers
      (4.3 days versus 3.0 days, of the preceding 30 days). Public health initiatives
      should be designed to promote the health and well-being of both care recipients
      and caregivers.

PMID- 17538529
TI  - Acanthamoeba keratitis multiple states, 2005-2007.
AB  - In May 2006, the Illinois Department of Public Health (IDPH) informed CDC about a
      possible increase in Acanthamoeba keratitis (AK) at an ophthalmology center in
      Illinois during the preceding 3 years. The University of Illinois at Chicago
      (UIC) was investigating this possible increase. In October 2006, IDPH updated CDC
      about the ongoing UIC investigation. At that time, CDC informally contacted
      multiple ophthalmology centers in the United States to assess whether the
      potential increase in cases extended beyond Illinois. Responses from the
      ophthalmology centers were inconclusive. In January 2007, CDC initiated a
      retrospective survey of 22 ophthalmology centers nationwide to assess whether
      cases were increasing throughout the United States. In March 2007, data received
      from 13 centers demonstrated an increase in culture-confirmed cases of AK with
      wide geographic distribution. The increase in cases had begun in 2004 and
      continued to the present. On March 16, 2007, CDC initiated a multistate
      investigation to look for risk factors associated with this increase in AK cases.
      This report summarizes recent preliminary results of that investigation, which,
      indicated an association with AK in soft contact lens wearers who used Advanced
      Medical Optics (Santa Ana, California) Complete MoisturePlus (AMOCMP)
      multipurpose cleaning solution. CDC and the Food and Drug Administration (FDA)
      are taking steps to notify the public and the medical and public health
      communities of this preliminary association. The manufacturer has undertaken a
      voluntary recall of the product.

PMID- 17538530
TI  - No consensus on glutamate.

PMID- 17538531
TI  - Development of a food frequency questionnaire for the assessment of quercetin and
      naringenin intake.
AB  - OBJECTIVES: To measure the relationship between quercetin and naringenin intakes
      as estimated by food frequency questionnaire (FFQ), and the urinary excretion of
      quercetin and naringenin aglycones after their enzymatic hydrolysis in human
      volunteers. SUBJECTS AND METHODS: Volunteers were recruited via the Human
      Nutrition Unit volunteer databank at the Institute of Food Research, Norwich.
      Sixty-three volunteers were recruited into the study, of which 14 were excluded
      and 49 completed the study. A modified FFQ was developed and used to estimate
      daily intake of quercetin and naringenin in 49 healthy volunteers who also
      provided five 24-h urine samples over a 2-week period. Urinary excretion of
      quercetin and naringenin metabolites was determined by solid-phase extraction and
      high-pressure liquid chromatography. RESULTS: The estimated mean intakes of
      quercetin and naringenin were 29.4 mg (s.d. 15.0) and 58.1 mg (s.d. 62.7) per
      day, respectively. Mean urinary excretion of quercetin was 60.1 microg (s.d.
      33.1) and that of naringenin was 0.56 mg (s.d. 0.4). The correlation between FFQ
      estimated intake of quercetin and naringenin and levels excreted in the urine
      were r=0.82 (P<0.0001) and r=0.25 (P=0.05), respectively. CONCLUSIONS: We
      observed a statistically significant correlation between the urinary excretion of
      quercetin and naringenin metabolites and their dietary intake as estimated by
      FFQ. Use of FFQs in epidemiological studies requiring an estimate of flavonoid
      intake seems justified.

PMID- 17538532
TI  - Low-energy reporting and duration of recording period.
AB  - Three-day, rather than 7-day, food records are frequently used because mis
      reporting of food intake is believed to increase with recording period. Data from
      the National Diet and Nutrition Survey of adults were used to explore trends in
      reported energy intake (REI) with day of recording and to compare average REIs
      from Thursday to Saturday and from Sunday to Tuesday to the complete 7-day
      record. Although REIs decreased from days 2 to 7, this was by a quantitatively
      insignificant 49 kJ per day (P=0.026) and well within the measurement error of
      recorded food intakes. Furthermore, REIs were lowest on the first recording day.
      The 3- and 7-day averages were similar (mean difference 0.039 (s.d.+/-1.0) MJ
      (NS), range -3.3 to +4.2 MJ). However, the difference was greater for those
      reporting higher than average energy intakes because of higher REIs on weekend
      days. Food intake reporting periods of longer than 3 days and ideally 7 days are
      preferable.

PMID- 17538533
TI  - Vitamin D status and health correlates among German adults.
AB  - OBJECTIVE: To analyze vitamin D status based on serum 25-hydroxyvitamin D (25OHD)
      measurements, its determinants and health correlates in a representative sample
      of German adults. SUBJECTS: A total of 1763 men and 2267 women, 18- to 79-year
      old, who participated in the representative German National Health Interview and
      Examination Survey 1998 and the integrated German Nutrition Survey. RESULTS: The
      median vitamin D intake from both diet and supplements did not meet the
      recommended level of 5 microg/day, in either men (2.8 microg/day) or women (2.3
      microg/day). Altogether 80.9% of men and 88.5% of women had vitamin D intakes
      below this level. Moderate (12.5-25 nmol/l serum 25OHD levels) and mild (25-50
      nmol/l) vitamin D deficiency was prevalent in the adult population in Germany,
      even in younger age groups. Overall, 57% of men and 58% of women had vitamin D
      levels below 50 nmol/l. Among 65- to 79-year-old women, the proportion amounted
      to 75%, even during the sunnier half of the year. In sex-specific multiple linear
      regression models, independent determinants of serum 25OHD levels consistently
      included season, vitamin D intake from both diet and supplements, physical
      activity and living in a partnership. In addition, age and current menopausal
      hormone use contributed to the model among women, as opposed to time of day of
      blood sampling and body mass index (marginally) among men. Significantly lower
      serum 25OHD levels were observed in women with hypertension, cardiovascular
      diseases and noninsulin-treated diabetes mellitus as well as in men with insulin
      treated diabetes mellitus compared with nonaffected participants. CONCLUSIONS:
      Vitamin D deficiency is a public health issue in Germany. We identified a number
      of determinants with potential for primary prevention of vitamin D deficiency.
      Risk and benefits of preventive actions need to be examined in further studies.

PMID- 17538534
TI  - Studies of a urinary biomarker of dietary inorganic sulphur in subjects on diets
      containing 1-38 mmol sulphur/day and of the half-life of ingested 34SO4(2-).
AB  - OBJECTIVE: Sulphites are widely used food additives that may damage health, hence
      limits are set on their use. They are excreted in urine as sulphate, along with
      sulphate derived from sulphur amino acids. Dietary intakes of sulphites are hard
      to determine, so we have tested the utility of urinary nitrogen:sulphate ratio as
      a biomarker of inorganic sulphur (IS) intake. Additionally we determined the half
      life of ingested (34)SO(4)(2-) from its urinary excretion. SUBJECTS: Twenty
      healthy adult subjects were recruited by poster advertisement, for a 24-h study
      where they ate specified foods, which were high in IS, in addition to their
      normal diet. The half-life of ingested (34)SO(4)(2-) was assessed in five healthy
      volunteers, given 5.9 mmols of Na(2)(34)SO(4) as a single dose and collecting all
      urine specimens for 72-96 h. Urine and duplicate diets from three previously
      conducted studies were analysed for nitrogen and sulphate content, thus expanding
      the range of IS intakes for evaluation. METHODS: Duplicate diets were analysed
      for IS content by ion exchange chromatography, while IS intake was predicted from
      urinary sulphate (g/day S)-(urinary nitrogen (g/day)/18.89). (32)S:(34)S ratios
      were determined by liquid chromatography mass spectrometry/mass spectrometry.
      RESULTS: The range of IS intake was 1.3-37.5 mmol S/day. Actual and predicted IS
      intakes were mmol/day+/-s.e. 9.2+/-0.65 and 7.0+/-0.45, respectively, and were
      correlated r=0.60 (n=108). The mean half-life of ingested (34)SO(4)(2-) was 8.2
      h. CONCLUSIONS: From a 24-h urine collection, IS intake from the habitual diet
      can be determined for groups of individuals. To predict individual intakes of IS,
      which may include high sporadic amounts from beer and wine, at least 48 h of
      urine collection would be required.

PMID- 17538535
TI  - Snacks are important for fat and vitamin intakes among rural African women: a
      cross-sectional study from Malawi.
AB  - OBJECTIVE: To estimate the contribution of energy and selected nutrients from
      foods eaten as snacks and as meals. SUBJECTS AND METHODS: Forty-four nonpregnant
      women in the reproductive age, of whom 20 were lactating, participated in this
      study. Women from rural households were randomly selected and energy and nutrient
      intakes were estimated using 2 days' observed weighed food record. Snacks eaten
      between meals were estimated by weighed food record as well as recall, thrice per
      day. RESULTS: The largest proportions (mean+/-s.e.) of fat (33+/-3.6%), vitamin C
      (36+/-4.1%) and a large proportion of vitamin A (30+/-4.4%) intakes were from
      snacks. Furthermore, snacks provided 20% of the energy intakes. CONCLUSION:
      Snacks are important for energy and nutrient intakes and adequacies in rural
      African women and have the potential to combat energy and nutrient deficiencies
      in low-income countries.

PMID- 17538536
TI  - Selenium levels of Estonians.
AB  - BACKGROUND: The objective of this study is to sum up the dietary selenium intake
      of the Estonian people according to the serum selenium concentrations.
      SUBJECTS/METHODS: This research compiles the information published in the
      literature about the levels of selenium in the serum of the Estonian people. We
      compare these results with the findings obtained from the analyses of serum
      samples gathered by us in the 1990s in Estonia. RESULTS: The selenium
      concentration in sera of 404 Estonians ranged from 26 to 116 microg/l; the mean
      was 75 microg/l. The selenium contents of Estonians were at a similar level as
      reported for Finns before the selenium supplementation of fertilizers carried out
      in Finland in 1984. CONCLUSION: In view of the selenium concentration in the
      sera, we suggest that the dietary selenium intake among the Estonian people might
      be scarce, and Estonian authorities should consider in their nutrition policies
      the possible low intake of selenium of Estonians.

PMID- 17538537
TI  - Fish oil after abdominal aorta aneurysm surgery.
AB  - OBJECTIVE: Fish oil (FO) may attenuate the inflammatory response after major
      surgery such as abdominal aortic aneurysm (AAA) surgery. We aimed at evaluating
      the clinical impact and safety aspects of a FO containing parenteral nutrition
      (PN) after AAA surgery. METHODS: Intervention consisted in 4 days of either
      standard (STD: Lipofundin medium-chain triglyceride (MCT): long-chain
      triglyceride (LCT)50%-MCT50%) or FO containing PN (FO: Lipoplus: LCT40%-MCT50%
      FO10%). Energy target were set at 1.3 times the preoperative resting energy
      expenditure by indirect calorimetry. Blood sampling on days 0, 2, 3 and 4.
      Glucose turnover by the (2)H(2)-glucose method. Muscle microdialysis. CLINICAL
      DATA: maximal daily T degrees, intensive care unit (ICU) and hospital stay.
      RESULTS: Both solutions were clinically well tolerated, without any differences
      in laboratory safety parameters, inflammatory, metabolic data, or in organ
      failures. Plasma tocopherol increased similarly; with FO, docosahexaenoic and
      eicosapentaenoic acid increased significantly by day 4 versus baseline or STD. To
      increased postoperatively, with a trend to lower values in FO group (P=0.09).
      After FO, a trend toward shorter ICU stay (1.6+/-0.4 versus 2.3+/-0.4), and
      hospital stay (9.9+/-2.4 versus 11.3+/-2.7 days: P=0.19) was observed.
      CONCLUSIONS: Both lipid emulsions were well tolerated. FO-PN enhanced the plasma
      n-3 polyunsaturated fatty acid content, and was associated with trends to lower
      body temperature and shorter length of stay.

PMID- 17538538
TI  - Relative validity of a food frequency questionnaire used in the Inter99 study.
AB  - OBJECTIVE: To evaluate the validity of the Inter99 food frequency questionnaire
      (FFQ) compared with a 28-days' diet history and biomarkers. SUBJECTS: A random
      sample of 13 016 individuals were drawn from a general population and invited for
      a health screening programme. Participation rate was 52.5%. All high-risk
      individuals were re-invited for assessment after 1 and 3 years and completed a
      198-item FFQ at all three occasions. Participants attending for 3 years follow-up
      were invited to participate in the validation study, including a 28-days' diet
      history, a 24-h urine collection and a fasting blood sample. Overall, 264
      subjects participated. RESULTS: Spearman's rank correlation coefficients between
      the two dietary methods ranged from 0.31(beta-carotene) to 0.64 (fruits) in men
      and from 0.31 (polyunsaturated fat and sodium) to 0.64 (fruits) for women. The
      proportion of individuals classified in the same or adjacent quintiles were, on
      average, 72% for men and 69% for women. Gross misclassification was found on
      average in 2%. The correlation coefficients of the residuals ranged from 0.27
      (sodium) to 0.61 (fruits) for men and from 0.21 (sodium) to 0.62 (B12-vitamin)
      for women. Correlation coefficients between fruit and vegetable intake and
      carotenoids ranged from -0.08 (lycopene) to 0.44 (alpha-carotene). For the
      residuals the correlation coefficients ranged from -0.004 (lycopene) to 0.47
      (alpha-carotene). CONCLUSION: The Inter99 FFQ and the residuals of the intake
      provide acceptable classification of individuals according to their dietary
      intakes and the FFQ gives a good quantitative measurement of key dietary
      components.

PMID- 17538539
TI  - Dose-response effects of different plant sterol sources in fat spreads on serum
      lipids and C-reactive protein and on the kinetic behavior of serum plant sterols.
AB  - OBJECTIVE: To test the dose-response effect on low-density lipoprotein
      cholesterol (LDL-c) of plant sterols (PS) from different sources in a low-fat
      spread. METHODS: Dose responses of soybean oil (BO), tall oil (TO) and a mix of
      tall oil and rapeseed oil (TO/RP) as fatty acid esters were tested in a parallel
      design in free-living subjects recruited from the general community who had
      elevated cholesterol concentrations. Subjects received either control for 6 weeks
      or 1.6 g PS per day for 3 weeks, then 3.0 g/day for 3 weeks. RESULTS: LDL-c was
      lowered significantly by consumption of 1.6 g/day of PS (-10.4%, range -7.3 to 
      11.4%). Increasing the dose to 3.0 g/day modestly reduced LDL-c concentrations
      further to -14.7%. TO, containing 78% sitosterol, produced an increase in serum
      sitosterol of 6.5 nmol/ml, while BO, containing only 27% campesterol, produced an
      increase in serum campesterol of 9.5 nmol/ml in 6 weeks. After PS withdrawal,
      serum sterols declined by 50% within 2 weeks. CONCLUSION: Different PS sources
      were equally effective in lowering serum LDL-c concentrations. The decrease in
      absolute concentrations of LDL-c was dependent on the baseline concentrations.

PMID- 17538540
TI  - Variation in fasting and non-fasting serum enterolactone concentrations in women
      of the Malmo Diet and Cancer cohort.
AB  - OBJECTIVES: The aim of this study was to examine the variation of enterolactone
      from fasting and non-fasting blood of middle-aged healthy women eating a normal
      diet to determine the usefulness of a single sample in epidemiological studies.
      SUBJECTS AND METHODS: Twenty-six women born between 1940 and 1950 were recruited
      within the Malmo Diet and Cancer cohort. Three non-fasting and two overnight
      fasting samples were collected from each individual during a 5-week period.
      Twenty-one participated in all measurements. Enterolactone concentrations were
      analyzed by time-resolved fluoroimmunoassay. RESULTS: The within-subject and
      between-subject variations (coefficient of variations, CV) were estimated to 59
      and 89% respectively for fasting samples and 71 and 67% for non-fasting samples.
      The intraclass correlation coefficients (ICC) were estimated to 0.66 (95%
      confidence interval (CI) 0.35-0.84) for fasting and 0.48 (95% CI, 0.22-0.72) for
      non-fasting samples. CONCLUSIONS: Although the estimated ICC for blood samples
      was moderate, it indicates that enterolactone levels of both fasting and non
      fasting blood samples should be useful in future projects within the Malmo Diet
      and Cancer cohort.

PMID- 17538541
TI  - The effect of a school-based weekly iron supplementation delivery system among
      anemic schoolchildren in the Philippines.
AB  - OBJECTIVE: To determine the effect of a school-based weekly iron supplementation
      delivery system (WISDS) on the prevalence of anemia among anemic schoolchildren.
      SUBJECTS AND METHODS: Two hundred and forty-two Filipino schoolchildren aged 6-12
      years with hemoglobin (Hb) concentration <12 g/dl and enrolled for school year
      2003-2004. UNICEF iron-folate tablets containing 60 mg elemental iron and 0.40 mg
      folic acid were given weekly through directly observed supplementation by the
      teachers for 27 weeks. Compliance to iron supplementation was monitored by the
      teachers and was recorded using a monitoring form and a supplementation calendar.
      Hb concentration, weight and height were determined at baseline and at post
      intervention. RESULTS: At post-intervention, the participants' mean Hb
      concentration increased by 0.4 g/dl (95% confidence interval =0.3, 0.5 g/dl;
      P<0.0001), anemia prevalence was reduced by 53.7, and 84.3% of the participants
      had 100% compliance to supplementation. CONCLUSIONS: The school-based WISDS
      reduced anemia prevalence among anemic schoolchildren and resulted in high
      compliance to and coverage of iron supplementation.

PMID- 17538542
TI  - Seasonal variations and trends in weight and arm circumference of non-pregnant
      rural Senegalese women, 1990-1997.
AB  - OBJECTIVE: To describe levels, monthly variations and trends in weight and arm
      circumference of non-pregnant lactating women living in the Sahel, characterized
      by one short yearly rainy season (July-October). METHODS: A mixed unbalanced
      cross-sectional longitudinal observational study conducted at 3, 5, 7 and 10
      months postpartum among 3869 women living in the Sine area in central Senegal who
      had brought their infants into dispensaries for immunization from January 1990 to
      February 1997, and 1-5 consecutive children per woman (26 106 visits). RESULTS:
      Mean weight was 55.7 kg (s.d.: 7.1), but it varied by 2.5-3.9 kg each year, from
      high means during the dry season (March-May) to low means at the end of the rainy
      season (September-November). The prevalence of underweight, overweight and
      obesity (body mass index (BMI)<18.5, 25-29.9 and >30 kg/m(2), respectively) was
      7.6% (95% confidence interval: 7.3, 7.9), 6.4% (6.1, 6.7) and 0.4% (0.3, 0.4),
      but varied strongly by season (P<0.0001 for all). Unlike weight, mean arm
      increased during the early rains, a peak season of agricultural work (+0.10
      cm/month (s.d.: 0.6) from June to August vs -0.35 kg/month (s.d.: 1.1) for
      weight). BMI and arm circumference were positively associated with age (mean:
      20.8 vs 22.2 kg/m(2) and 25.3 vs 27.4 cm, at 20-24 and 40-49 years, respectively,
      P<0.0001 for both). CONCLUSIONS: Season was a major determinant of the
      anthropometric status of rural African women. Negative energy balance reduced
      body weight from the onset of agricultural labour, while arm circumference
      increased during early rains, probably due to high physical activity.

PMID- 17538543
TI  - Dietary intake of B(6-9-12) vitamins, serum homocysteine levels and their
      association with depressive symptoms: the Zutphen Elderly Study.
AB  - OBJECTIVE: Low B-vitamin status and high levels of serum homocysteine are found
      in depressed inpatients, but results of population-based studies of this
      association are inconclusive. We investigated whether a low dietary intake of B(6
      9-12) vitamins and high levels of serum homocysteine are associated with
      depressive symptoms in elderly men. METHODS: The study sample included a total of
      332 men aged 70-90 years who were free from cardiovascular diseases and diabetes
      at baseline in 1990. Depressive symptoms were measured with the Zung Self-rating
      Depression Scale at baseline in 1990 and dietary factors with the crosscheck
      dietary history method in 1985 and 1990. Serum levels of homocysteine were
      obtained in 1985. Multiple linear and logistic regression analyses were
      performed. RESULTS: Dietary intake of folate (-1.19, 95% CI -2.03; -0.36) and
      vitamin B(6) (-2.09, 95% CI -2.92; -1.26) per standard deviation increase was
      associated with lower levels of serum homocysteine, while vitamin B(12) was not
      associated with serum homocysteine. Intake of folate, vitamin B(6), vitamin B(12)
      and levels of serum homocysteine were not related to depressive symptoms.
      CONCLUSIONS: Our results do not support the hypothesis that a low dietary intake
      of B(6-9-12) vitamins and high levels of serum homocysteine are related to
      depression in healthy elderly men.

PMID- 17538544
TI  - No adverse events after simultaneous administration of 50 000 IU vitamin A and
      Bacille Calmette-Guerin vaccination to normal-birth-weight newborns in Guinea
      Bissau.
AB  - OBJECTIVE: To determine whether the combined intervention of 50 000 IU vitamin A
      administered together with Bacille Calmette-Guerin (BCG) vaccination at birth was
      associated with adverse events, in particular bulging fontanels and adverse
      reactions to BCG. SUBJECTS/METHODS: From an ongoing trial, 2145 infants
      randomized to 50 000 IU vitamin A or placebo with BCG vaccination were recruited.
      Adverse events were monitored in two different ways: (A) daily clinical
      examinations by a medical doctor during the first 3 days post supplementation;
      (B) weekly interviews by a trained assistant during the first month post
      supplementation. RESULTS: In part A, 1271 infants were enrolled, in part B 2078.
      Vitamin A supplementation (VAS) was associated with a relative risk (RR) of
      bulging fontanels of 1.16 (95% confidence interval (CI)=0.82-1.65). The rate of
      health care contacts and various symptoms during the first month were comparable
      between the groups. VAS was associated with larger peak local reactions to BCG
      vaccination in boys, but not in girls (P-value for test of interaction between
      VAS and sex=0.02). CONCLUSION: 50 000 IU vitamin A with BCG was not associated
      with adverse events. The observed sex-differential effect of VAS on local
      reaction to BCG is in line with other observations of sex-differential effects of
      VAS.

PMID- 17538545
TI  - Uridine supplementation in HIV lipoatrophy: pilot trial on safety and effect on
      mitochondrial indices.
AB  - OBJECTIVES: Uridine abrogates mitochondrial toxicities of nucleoside reverse
      transcriptase inhibitor in adipocyte cell culture. We aim to study the effect of
      uridine supplementation on human adipocyte mitochondrial DNA (mtDNA) levels in
      subjects with human immunodeficiency (HIV) lipoatrophy. METHODS: Sixteen patients
      with lipoatrophy on stavudine-containing antiretroviral therapy were enrolled,
      and received NucleomaxX, a dietary supplement with a high bioavailability of
      uridine (36 g TID every other day for 16 weeks). Patients were then followed off
      uridine for another 16 weeks. Highly active antiretroviral therapy remained
      unchanged during the trial. RESULTS: Fourteen patients completed the study. Two
      subjects dropped out before week 4 for study-unrelated reasons. No adverse events
      were noted throughout the study. HIV-1 RNA, CD4 counts, liver enzymes and
      hemoglobin remained unchanged. Body mass index, lactate, lipids, insulin and
      homeostasis model assessment of insulin resistance were unaltered. Fat and
      peripheral blood and mononuclear cell mtDNA levels did not correlate with each
      other and exhibited no changes throughout the study. Lipoatrophy scores by
      patients and physician improved significantly at weeks 16 and 32 compared to
      study entry. CONCLUSION: In this pilot study, NucleomaxX was safe, well tolerated
      without apparent deleterious effect on HIV indices. In contrast to in vitro data,
      NucleomaxX did not lead to changes in fat or blood mtDNA levels.

PMID- 17538546
TI  - Iron deficiency and anemia: disparity exists between children in American Samoa
      and children living within the US.
AB  - BACKGROUND/OBJECTIVES: Healthy People 2010 emphasizes elimination of health
      disparity and improvements in anemia and iron deficiency (ID). The study purpose
      was to (1) determine the prevalence of anemia, ID and ID anemia (IDA) in children
      living in American Samoa and (2) compare the prevalence to that found in children
      living in the United States. SUBJECTS/METHODS: A total of 211 children from
      American Samoa, aged 1-5 years of age, participated in this cross-sectional
      study. Prevalence of anemia, ID and IDA were determined and comparison made using
      data obtained from children living in the United States. Anemia was diagnosed as
      hemoglobin (Hb) <110.0 g/l, ID as erythrocyte protoporphyrin (EP) >70 mumol/mol
      heme and IDA as Hb <110.0 g/l and EP >70 mumol/mol heme. RESULTS: Anemia, ID and
      IDA prevalence was 33, 70 and 33%, respectively. The results of children from the
      United States were as follows: anemia, 9%; ID, 10% and IDA, 2%. Within American
      Samoan children, ID is positively associated with being breastfed <6 months
      (P<0.05) and anemia and IDA with lower household income (P<0.05; P<0.01). Mean Hb
      was significantly lower (P<0.001) and mean EP was significantly higher (P<0.001)
      than those within children living in the United States. CONCLUSION: To meet
      Healthy People 2010 goals in children aged 1-2 years, the prevalence of ID in
      children living in American Samoa would need to decrease from 83 to 5% and in
      children aged 3-5 years from 59 to 1%. It is critical to ensure that populations
      within the United States and its territories are provided appropriate resources
      to promote health and prevent disease.

PMID- 17538547
TI  - The importance of bioavailability of dietary iron in relation to the expected
      effect from iron fortification.
AB  - BACKGROUND: The most common method of combating iron deficiency is iron
      fortification, especially in developing countries. However, few studies have
      shown a significant effect on iron status following iron fortification of low
      bioavailability diets. OBJECTIVE: To investigate how iron fortification and
      dietary modifications affect iron absorption and rates of changes in iron stores.
      METHODS: Research has made it possible to predict both iron absorption and the
      effects of iron fortification and diet modifications on iron stores using
      recently developed algorithms. Iron absorption and rate of change in iron stores
      were calculated from nine diets representing a broad range of iron
      bioavailability and iron contents. The calculations were related to the main
      target group for iron fortification, that is, women of reproductive age having
      empty stores but normal haemoglobin concentrations. RESULTS: As the only measure,
      iron fortification has practically no effect on iron status if the original diet
      has low bioavailability. However, after dietary modifications such a diet shows a
      positive effect on iron stores. The combined action of fortification (6 mg/day)
      and modest bioavailability changes in a low bioavailability diet results
      approximately in 40 and 70% greater increases in iron stores than through iron
      fortification or dietary modification alone. CONCLUSIONS: It is difficult to
      achieve good effects on iron status from iron fortification as the only measure
      if the diet has low bioavailability. Both dietary modifications as well as iron
      fortification are required to improve effectively the iron status of a
      population.

PMID- 17538548
TI  - Novel statistical tools for monitoring the safety of marketed drugs.
AB  - Robust tools for monitoring the safety of marketed therapeutic products are of
      paramount importance to public health. In recent years, innovative statistical
      approaches have been developed to screen large post-marketing safety databases
      for adverse events (AEs) that occur with disproportionate frequency. These
      methods, known variously as quantitative signal detection, disproportionality
      analysis, or safety data mining, facilitate the identification of new safety
      issues or possible harmful effects of a product. In this article, we describe the
      statistical concepts behind these methods, as well as their practical application
      to monitoring the safety of pharmaceutical products using spontaneous AE reports.
      We also provide examples of how these tools can be used to identify novel drug
      interactions and demographic risk factors for adverse drug reactions. Challenges,
      controversies, and frontiers for future research are discussed.

PMID- 17538549
TI  - Benefit/risk ratio of statins in primary prevention.

PMID- 17538550
TI  - Cholesterol--when is lower better?
AB  - When recommending how to treat a patient's lipid profile with drugs, there are
      two common misinterpretations of the data that are often quoted to support the
      current enthusiasm for the lower the cholesterol, the better.

PMID- 17538551
TI  - The challenge of treating biofilm-associated bacterial infections.
AB  - Biofilm formation is a crucial step in the pathogenesis of many subacute and
      chronic bacterial infections, including foreign body-related infections. Biofilms
      are difficult to eradicate with conventional antimicrobial agents. Bacterial
      biofilms have several potential antimicrobial resistance mechanisms.
      Antimicrobial resistance mechanisms may act concurrently, and in some cases,
      synergistically. Persister cells play a major role in the tolerance of biofilm
      bacteria to antimicrobial agents. Understanding the mechanisms involved in
      biofilm-associated antimicrobial resistance is key to development of new
      therapeutic strategies.

PMID- 17538552
TI  - Regulatory considerations for determining postmarketing study commitments.
AB  - Postmarketing Study Commitments (PMCs) are, most commonly, agreements made by
      pharmaceutical companies at the time of an FDA approval to perform a study or
      studies to elucidate further characteristics of the drug under consideration. The
      role of PMCs in drug regulation has come under considerable scrutiny in recent
      years, particularly as discussions of drug safety have intensified. Although
      these agreed-upon PMCs are described in FDA regulations, such PMCs are not sought
      by FDA with every approval, and completion of the agreed-upon studies is not a
      requirement for the drug's sponsor (there are required PMCs under certain
      regulatory provisions and these are discussed below). Requests by FDA at the time
      of regulatory approval for studies under PMCs have been a common practice for
      many years. When made, PMCs are described in the approval letters and are
      therefore publicly available. Concerns over whether PMCs were being duly
      performed, reported, and reviewed by FDA were addressed in the FDA Modernization
      Act of 1997, which required more detailed reporting by manufactures on their
      progress in meeting the PMCs and required FDA to report certain information
      publicly.

PMID- 17538553
TI  - Pharmacometrics at FDA: evolution and impact on decisions.
AB  - Drug development and regulatory decisions are driven by information that is
      compiled primarily from clinical trials and other supportive experiments, but
      also through clinical experience in the post-market period. The wisdom of these
      decisions determines the efficiency of drug development, the decision to approve
      the drug, and the resultant drug product quality including guidance on how to use
      the product known as the label. Although the decisions are usually simple in
      nature (e.g., trial design and project progression at the company, product and
      labeling approval at the Food and Drug Administration (FDA)), the information
      informing the decision is complex and diverse.

PMID- 17538561
TI  - Rheumatology without borders.

PMID- 17538562
TI  - Bone, not cartilage, should be the major focus in osteoarthritis.

PMID- 17538563
TI  - Thalidomide for rheumatic disease: the best of both worlds?

PMID- 17538564
TI  - Adult-onset Still's disease: can recent advances in our understanding of its
      pathogenesis lead to targeted therapy?
AB  - Adult-onset Still's disease is a rare systemic inflammatory disease of unknown
      etiology, characterized by daily high, spiking fevers, evanescent rash, and
      arthritis. There is no single diagnostic test for adult-onset Still's disease;
      rather, the diagnosis is based on clinical criteria and necessitates the
      exclusion of infectious, neoplastic, and other 'autoimmune' diseases.
      Proinflammatory cytokines such as interleukin (IL)-1, IL-6, and IL-18, interferon
      gamma, tumor necrosis factor, and macrophage colony-stimulating factor are
      elevated in patients with adult-onset Still's disease and are thought to have a
      major role in the pathogenesis of the disease. Treatment consists of nonsteroidal
      anti-inflammatory drugs, corticosteroids, immunosuppressants (methotrexate, gold,
      azathioprine, leflunomide, cyclosporin, and cyclophosphamide), intravenous
      immunoglobulin, and cytokine (tumor necrosis factor, IL-1 and IL-6) inhibitors.
      Recent advances in basic immunology have enhanced our ability to hinder the
      pathogenic mechanisms associated with adult-onset Still's disease and have led to
      a paradigm shift where targeted treatments have an increasingly important role.

PMID- 17538565
TI  - Emerging targets of biologic therapies for rheumatoid arthritis.
AB  - Advances in molecular biology and the clinical success of strategies that target
      tumor necrosis factor (TNF) have led to further research into the pathophysiology
      of human rheumatoid arthritis. Several novel therapeutic targets have emerged
      from these efforts, including not only molecules that regulate TNF (e.g. TNF
      alpha converting enzyme), the complex cytokine network (e.g. interleukin [IL]-6,
      IL-15, IL-17) and several adipokines, but also targets that originate from
      cellular and subcellular components of the disease. Strategies that aim at
      cellular targets include antibodies to CD20 or BLyS (also known as TNF ligand
      family member 13b), which deplete or inhibit B cells, as well as approaches that
      interfere with membrane-derived microparticles. Components of subcellular
      pathways, which are predominantly upstream of the central regulator of
      transcription nuclear factor kappaB, have also been studied. Of these, strategies
      that target mitogen-activated protein kinases have a leading role and are on the
      verge of clinical use; approaches that target specific molecules such as Janus
      kinases, signal transducer and activator of transcription proteins, and
      suppressor of cytokine signaling proteins also seem to show promise and might
      have a clinical application in the future.

PMID- 17538566
TI  - Biological markers in osteoarthritis.
AB  - Osteoarthritis (OA) is a progressive disorder characterized by destruction of
      articular cartilage and subchondral bone, and by synovial changes. The diagnosis
      of OA is generally based on clinical and radiographic changes, which occur fairly
      late during disease progression and have poor sensitivity for monitoring disease
      progression. Progression of joint damage is likely to result primarily from an
      imbalance between cartilage degradation and repair, so measuring markers of these
      processes would seem a promising approach to improve the prediction of disease
      progression at the individual level. Moreover, genetic markers might be useful
      predictors of prognosis. The lack of fully effective, chondroprotective
      medications has limited the use of such potential markers to monitor the effect
      of treatment for OA. Nevertheless, owing to their dynamic changes in response to
      treatment, biological markers might provide relevant information more rapidly
      than imaging techniques (such as radiography and MRI) can, and should contribute
      to our understanding of mechanisms that underlie the clinical efficacy of OA
      treatments. Most of the identified genes involved in OA encode signal
      transduction proteins, which provide the potential for novel therapeutic
      approaches. In this Review, we will use the recently proposed BIPED (i.e. burden
      of disease, investigative, prognostic, efficacy of intervention and diagnostic)
      classification of OA markers to describe the potential usage of a given marker.

PMID- 17538567
TI  - Thrombotic microangiopathic hemolytic anemia in a patient with SLE: diagnostic
      difficulties.
AB  - BACKGROUND: A 19-year-old woman with newly diagnosed systemic lupus erythematosus
      (SLE) presented with hemolytic anemia, thrombocytopenia, hypertension, tonic
      clonic seizures, blurry vision, nephrotic syndrome and renal insufficiency.
      INVESTIGATIONS: At a general hospital, the investigations included brain MRI,
      echocardiography, laboratory tests including measurement of the amount of protein
      excreted daily, platelet count, levels of lactate dehydrogenase, creatinine and
      anticardiolipin antibodies, direct Coombs' test, peripheral blood smear, and
      measurement of blood pressure. At a tertiary institution the investigations
      included physical examination, electroencephalography, brain MRI, magnetic
      resonance angiography, repetition of laboratory tests plus measurement of von
      Willebrand factor-cleaving protease activity, measurement of levels of antibodies
      to double-stranded DNA and platelets, and renal biopsy. DIAGNOSIS: Thrombotic
      microangiopathic hemolytic anemia with a possible underlying diagnosis of
      malignant hypertension, antiphospholipid antibody syndrome, catastrophic
      antiphospholipid antibody syndrome, thrombotic thrombocytopenic purpura, or
      active SLE. MANAGEMENT: At the general hospital, therapy included a single dose
      of intravenous cyclophosphamide 500 mg, eight daily plasma exchange treatments,
      three daily infusions of methylprednisolone 1 g followed by methylprednisolone 60
      mg every 8 h, an infusion of rituximab 657 mg and ultrafiltration via
      hemodialysis. At the tertiary institution, therapy included an infusion of
      cyclophosphamide 650 mg, aspirin 81 mg daily, prednisone 40 mg daily,
      mycophenolate mofetil 750 mg twice daily, and aggressive management of
      hypertension.

PMID- 17538568
TI  - Endochondral bone formation is involved in media calcification in rats and in
      men.
AB  - Arterial media calcification is often considered a cell-regulated process
      resembling intramembranous bone formation, implying a conversion of vascular
      tissue into a bone-like structure without a cartilage intermediate. In this
      study, we examined the association of chondrocyte-specific marker expression with
      media calcification in arterial samples derived from rats with chronic renal
      failure (CRF) and from human transplant donors. CRF was induced in rats with a
      diet supplemented with adenine. Vascular calcification was evaluated
      histomorphometrically on Von Kossa-stained sections and the expression of the
      chondrocyte markers sox9 and collagen II with the osteogenic marker core-binding
      factor alpha1 (cbfa1) was determined immunohistochemically. Media calcification
      was detected in more than half of the rats with CRF. In over half of the rats
      with severe media calcification, a typical cartilage matrix was found by
      morphology. All of the animals with severe calcification showed the presence of
      chondrocyte-like cells expressing the markers sox9, collagen II, and cbfa1. Human
      aorta specimens showing mild to moderate media calcification also showed sox9,
      collagen II, and cbfa1 expression. The presence of chondrocytes in association
      with calcification of the media in aortas of rats with CRF mimics endochondral
      bone formation. The relevance of this association is further demonstrated by the
      chondrogenic conversion of medial smooth muscle cells in the human aorta.

PMID- 17538569
TI  - Nitric oxide in shock.
AB  - Refractory hypotension with end-organ hypoperfusion and failure is an ominous
      feature of shock. Distributive shock is caused by severe infections (septic
      shock) or severe systemic allergic reactions (anaphylactic shock). In 1986, it
      was concluded that nitric oxide (NO) is the endothelium-derived relaxing factor
      that had been discovered 6 years earlier. Since then, NO has been shown to be
      important for the physiological and pathological control of vascular tone.
      Nevertheless, although inhibition of NO synthesis restores blood pressure, NO
      synthase (NOS) inhibition cannot improve outcome, on the contrary. This implies
      that NO acts as a double-edged sword during septic shock. Consequently, the focus
      has shifted towards selective inducible NOS (iNOS) inhibitors. The contribution
      of NO to anaphylactic shock seems to be more straightforward, as NOS inhibition
      abrogates shock in conscious mice. Surprisingly, however, this shock-inducing NO
      is not produced by the inducible iNOS, but by the so-called constitutive enzyme
      endothelial NOS. This review summarizes the contribution of NO to septic and
      anaphylactic shock. Although NOS inhibition may be promising for the treatment of
      anaphylactic shock, the failure of a phase III trial indicates that other
      approaches are required for the successful treatment of septic shock. Amongst
      these, high hopes are set for selective iNOS inhibitors. But it might also be
      necessary to shift gears and focus on downstream cardiovascular targets of NO or
      on other vasodilating phenomena.

PMID- 17538570
TI  - Two-photon microscopy: visualization of kidney dynamics.
AB  - The introduction of two-photon microscopy, along with the development of new
      fluorescent probes and innovative computer software, has advanced the study of
      intracellular and intercellular processes in the tissues of living organisms.
      Researchers can now determine the distribution, behavior, and interactions of
      labeled chemical probes and proteins in live kidney tissue in real time without
      fixation artifacts. Chemical probes, such as fluorescently labeled dextrans, have
      extended our understanding of dynamic events with subcellular resolution. To
      accomplish expression of specific proteins in vivo, cDNAs of fluorescently
      labeled proteins have been cloned into adenovirus vectors and infused by
      micropuncture to induce proximal tubule cell infection and protein expression.
      The localization and intensity of the expressed fluorescent proteins can be
      observed repeatedly at different time points allowing for enhanced quantitative
      analysis while limiting animal use. Optical sections of images acquired with the
      two-photon microscope can be 3-D reconstructed and quantified with Metamorph,
      Voxx, and Amira software programs.

PMID- 17538571
TI  - Ecology: global warming and amphibian losses.
AB  - Is global warming contributing to amphibian declines and extinctions by promoting
      outbreaks of the chytrid fungus Batrachochytrium dendrobatidis? Analysing
      patterns from the American tropics, Pounds et al. envisage a process in which a
      single warm year triggers die-offs in a particular area (for instance, 1987 in
      the case of Monteverde, Costa Rica). However, we show here that populations of
      two frog species in the Australian tropics experienced increasing developmental
      instability, which is evidence of stress, at least two years before they showed
      chytrid-related declines. Because the working model of Pounds et al. is
      incomplete, their test of the climate-linked epidemic hypothesis could be
      inconclusive.

PMID- 17538572
TI  - Ecology: the proximate cause of frog declines?
AB  - Pounds et al. argue that global warming contributes to amphibian declines by
      encouraging outbreaks of the chytrid fungus Batrachochytrium dendrobatidis.
      Although our findings agree with the climate-linked epidemic hypothesis, this
      pathogen is probably not the only proximate factor in such cases: in the
      Trasimeno Lake area of Umbria in central Italy, for example, the water frog Rana
      lessonae first declined in the late 1990s, yet chytridiomycosis was not observed
      until 2003 (refs 5, 6). Here we show that the chytrid was common there throughout
      1999-2002, in a previously unknown form that did not cause disease. We therefore
      think that the focus by Pounds et al. on a single pathogen is hard to justify
      because the host-parasite ecology is at present so poorly understood.

PMID- 17538578
TI  - No more hot air.

PMID- 17538577
TI  - Time for a medical.

PMID- 17538579
TI  - The safety catch.

PMID- 17538581
TI  - Weighing up the evidence.

PMID- 17538582
TI  - Man on a mission.

PMID- 17538584
TI  - Stormy opening to hurricane season.

PMID- 17538583
TI  - Academics strike back at spurious rankings.

PMID- 17538586
TI  - Changing course.

PMID- 17538587
TI  - Complex set of RNAs found in simple green algae.

PMID- 17538588
TI  - Science high on French political agenda.

PMID- 17538589
TI  - NIH calls halt to breeding chimps for research.

PMID- 17538590
TI  - Algae bloom again.

PMID- 17538593
TI  - Oceanography: churn, churn, churn.

PMID- 17538594
TI  - Obesity: the two faces of fat.

PMID- 17538595
TI  - Open journals' records to give reviewers their due.

PMID- 17538596
TI  - Pathologists needed to cope with mutant mice.

PMID- 17538597
TI  - Conflict and cancer research in Arizona.

PMID- 17538598
TI  - Treating astrology's claims with all due gravity.

PMID- 17538599
TI  - Can bans stimulate wildlife trade?

PMID- 17538603
TI  - Astrophysics: water worlds in the making.

PMID- 17538604
TI  - Ageing: when less is more.

PMID- 17538605
TI  - High-temperature superconductivity: local pairs and small surfaces.

PMID- 17538607
TI  - Evolutionary biology: animal personalities.

PMID- 17538608
TI  - Solid-state physics: a polariton laser.

PMID- 17538609
TI  - Protein science: discriminating taste of prions.

PMID- 17538610
TI  - Colour vision: seeing red.

PMID- 17538611
TI  - Obituary: Frank H. Westheimer (1912-2007).

PMID- 17538612
TI  - Two neurons mediate diet-restriction-induced longevity in C. elegans.
AB  - Dietary restriction extends lifespan and retards age-related disease in many
      species and profoundly alters endocrine function in mammals. However, no causal
      role of any hormonal signal in diet-restricted longevity has been demonstrated.
      Here we show that increased longevity of diet-restricted Caenorhabditis elegans
      requires the transcription factor gene skn-1 acting in the ASIs, a pair of
      neurons in the head. Dietary restriction activates skn-1 in these two neurons,
      which signals peripheral tissues to increase metabolic activity. These findings
      demonstrate that increased lifespan in a diet-restricted metazoan depends on cell
      non-autonomous signalling from central neuronal cells to non-neuronal body
      tissues, and suggest that the ASI neurons mediate diet-restriction-induced
      longevity by an endocrine mechanism.

PMID- 17538613
TI  - Water vapour and hydrogen in the terrestrial-planet-forming region of a
      protoplanetary disk.
AB  - Planetary systems (ours included) formed in disks of dust and gas around young
      stars. Disks are an integral part of the star and planet formation process, and
      knowledge of the distribution and temperature of inner-disk material is crucial
      for understanding terrestrial planet formation, giant planet migration, and
      accretion onto the central star. Although the inner regions of protoplanetary
      disks in nearby star-forming regions subtend only a few nano-radians, near
      infrared interferometry has recently enabled the spatial resolution of these
      terrestrial zones. Most observations have probed only dust, which typically
      dominates the near-infrared emission. Here I report spectrally dispersed near
      infrared interferometric observations that probe the gas (which dominates the
      mass and dynamics of the inner disk), in addition to the dust, within one
      astronomical unit (1 au, the Sun-Earth distance) of the young star MWC 480. I
      resolve gas, including water vapour and atomic hydrogen, interior to the edge of
      the dust disk; this contrasts with results of previous spectrally dispersed
      interferometry observations. Interactions of this accreting gas with migrating
      planets may lead to short-period exoplanets like those detected around main
      sequence stars. The observed water vapour is probably produced by the sublimation
      of migrating icy bodies, and provides a potential reservoir of water for
      terrestrial planets.

PMID- 17538614
TI  - Quantum oscillations and the Fermi surface in an underdoped high-Tc
      superconductor.
AB  - Despite twenty years of research, the phase diagram of high-transition
      temperature superconductors remains enigmatic. A central issue is the origin of
      the differences in the physical properties of these copper oxides doped to
      opposite sides of the superconducting region. In the overdoped regime, the
      material behaves as a reasonably conventional metal, with a large Fermi surface.
      The underdoped regime, however, is highly anomalous and appears to have no
      coherent Fermi surface, but only disconnected 'Fermi arcs'. The fundamental
      question, then, is whether underdoped copper oxides have a Fermi surface, and if
      so, whether it is topologically different from that seen in the overdoped regime.
      Here we report the observation of quantum oscillations in the electrical
      resistance of the oxygen-ordered copper oxide YBa2Cu3O6.5, establishing the
      existence of a well-defined Fermi surface in the ground state of underdoped
      copper oxides, once superconductivity is suppressed by a magnetic field. The low
      oscillation frequency reveals a Fermi surface made of small pockets, in contrast
      to the large cylinder characteristic of the overdoped regime. Two possible
      interpretations are discussed: either a small pocket is part of the band
      structure specific to YBa2Cu3O6.5 or small pockets arise from a topological
      change at a critical point in the phase diagram. Our understanding of high
      transition-temperature (high-T(c)) superconductors will depend critically on
      which of these two interpretations proves to be correct.

PMID- 17538615
TI  - Visualizing pair formation on the atomic scale in the high-Tc superconductor
      Bi2Sr2CaCu2O8+delta.
AB  - Pairing of electrons in conventional superconductors occurs at the
      superconducting transition temperature T(c), creating an energy gap Delta in the
      electronic density of states (DOS). In the high-T(c) superconductors, a partial
      gap in the DOS exists for a range of temperatures above T(c) (ref. 2). A key
      question is whether the gap in the DOS above T(c) is associated with pairing, and
      what determines the temperature at which incoherent pairs form. Here we report
      the first spatially resolved measurements of gap formation in a high-T(c)
      superconductor, measured on Bi2Sr2CaCu2O8+delta samples with different T(c)
      values (hole concentration of 0.12 to 0.22) using scanning tunnelling microscopy.
      Over a wide range of doping from 0.16 to 0.22 we find that pairing gaps nucleate
      in nanoscale regions above T(c). These regions proliferate as the temperature is
      lowered, resulting in a spatial distribution of gap sizes in the superconducting
      state. Despite the inhomogeneity, we find that every pairing gap develops locally
      at a temperature T(p), following the relation 2Delta/k(B)T(p) = 7.9 +/- 0.5. At
      very low doping (< or =0.14), systematic changes in the DOS indicate the presence
      of another phenomenon, which is unrelated and perhaps competes with electron
      pairing. Our observation of nanometre-sized pairing regions provides the missing
      microscopic basis for understanding recent reports of fluctuating superconducting
      response above T(c) in hole-doped high-T(c) copper oxide superconductors.

PMID- 17538616
TI  - Spin-based logic in semiconductors for reconfigurable large-scale circuits.
AB  - Research in semiconductor spintronics aims to extend the scope of conventional
      electronics by using the spin degree of freedom of an electron in addition to its
      charge. Significant scientific advances in this area have been reported, such as
      the development of diluted ferromagnetic semiconductors, spin injection into
      semiconductors from ferromagnetic metals and discoveries of new physical
      phenomena involving electron spin. Yet no viable means of developing spintronics
      in semiconductors has been presented. Here we report a theoretical design that is
      a conceptual step forward-spin accumulation is used as the basis of a
      semiconductor computer circuit. Although the giant magnetoresistance effect in
      metals has already been commercially exploited, it does not extend to
      semiconductor/ferromagnet systems, because the effect is too weak for logic
      operations. We overcome this obstacle by using spin accumulation rather than spin
      flow. The basic element in our design is a logic gate that consists of a
      semiconductor structure with multiple magnetic contacts; this serves to perform
      fast and reprogrammable logic operations in a noisy, room-temperature
      environment. We then introduce a method to interconnect a large number of these
      gates to form a 'spin computer'. As the shrinking of conventional complementary
      metal-oxide-semiconductor (CMOS) transistors reaches its intrinsic limit, greater
      computational capability will mean an increase in both circuit area and power
      dissipation. Our spin-based approach may provide wide margins for further scaling
      and also greater computational capability per gate.

PMID- 17538617
TI  - Observational evidence for an ocean heat pump induced by tropical cyclones.
AB  - Ocean mixing affects global climate and the marine biosphere because it is linked
      to the ocean's ability to store and transport heat and nutrients. Observations
      have constrained the magnitude of upper ocean mixing associated with certain
      processes, but mixing rates measured directly are significantly lower than those
      inferred from budget analyses, suggesting that other processes may play an
      important role. The winds associated with tropical cyclones are known to lead to
      localized mixing of the upper ocean, but the hypothesis that tropical cyclones
      are important mixing agents at the global scale has not been tested. Here we
      calculate the effect of tropical cyclones on surface ocean temperatures by
      comparing surface temperatures before and after storm passage, and use these
      results to calculate the vertical mixing induced by tropical cyclone activity.
      Our results indicate that tropical cyclones are responsible for significant
      cooling and vertical mixing of the surface ocean in tropical regions. Assuming
      that all the heat that is mixed downwards is balanced by heat transport towards
      the poles, we calculate that approximately 15 per cent of peak ocean heat
      transport may be associated with the vertical mixing induced by tropical
      cyclones. Furthermore, our analyses show that the magnitude of this mixing is
      strongly related to sea surface temperature, indicating that future changes in
      tropical sea surface temperatures may have significant effects on ocean
      circulation and ocean heat transport that are not currently accounted for in
      climate models.

PMID- 17538618
TI  - Life-history trade-offs favour the evolution of animal personalities.
AB  - In recent years evidence has been accumulating that personalities are not only
      found in humans but also in a wide range of other animal species. Individuals
      differ consistently in their behavioural tendencies and the behaviour in one
      context is correlated with the behaviour in multiple other contexts. From an
      adaptive perspective, the evolution of animal personalities is still a mystery,
      because a more flexible structure of behaviour should provide a selective
      advantage. Accordingly, many researchers view personalities as resulting from
      constraints imposed by the architecture of behaviour (but see ref. 12). In
      contrast, we show here that animal personalities can be given an adaptive
      explanation. Our argument is based on the insight that the trade-off between
      current and future reproduction often results in polymorphic populations in which
      some individuals put more emphasis on future fitness returns than others. Life
      history theory predicts that such differences in fitness expectations should
      result in systematic differences in risk-taking behaviour. Individuals with high
      future expectations (who have much to lose) should be more risk-averse than
      individuals with low expectations. This applies to all kinds of risky situations,
      so individuals should consistently differ in their behaviour. By means of an
      evolutionary model we demonstrate that this basic principle results in the
      evolution of animal personalities. It simultaneously explains the coexistence of
      behavioural types, the consistency of behaviour through time and the structure of
      behavioural correlations across contexts. Moreover, it explains the common
      finding that explorative behaviour and risk-related traits like boldness and
      aggressiveness are common characteristics of animal personalities.

PMID- 17538619
TI  - Incipient speciation by divergent adaptation and antagonistic epistasis in yeast.
AB  - Establishing the conditions that promote the evolution of reproductive isolation
      and speciation has long been a goal in evolutionary biology. In ecological
      speciation, reproductive isolation between populations evolves as a by-product of
      divergent selection and the resulting environment-specific adaptations. The
      leading genetic model of reproductive isolation predicts that hybrid inferiority
      is caused by antagonistic epistasis between incompatible alleles at interacting
      loci. The fundamental link between divergent adaptation and reproductive
      isolation through genetic incompatibilities has been predicted, but has not been
      directly demonstrated experimentally. Here we empirically tested key predictions
      of speciation theory by evolving the initial stages of speciation in experimental
      populations of the yeast Saccharomyces cerevisiae. After replicate populations
      adapted to two divergent environments, we consistently observed the evolution of
      two forms of postzygotic isolation in hybrids: reduced rate of mitotic
      reproduction and reduced efficiency of meiotic reproduction. This divergent
      selection resulted in greater reproductive isolation than parallel selection, as
      predicted by the ecological speciation theory. Our experimental system allowed
      controlled comparison of the relative importance of ecological and genetic
      isolation, and we demonstrated that hybrid inferiority can be ecological and/or
      genetic in basis. Overall, our results show that adaptation to divergent
      environments promotes the evolution of reproductive isolation through
      antagonistic epistasis, providing evidence of a plausible common avenue to
      speciation and adaptive radiation in nature.

PMID- 17538620
TI  - Symbolic arithmetic knowledge without instruction.
AB  - Symbolic arithmetic is fundamental to science, technology and economics, but its
      acquisition by children typically requires years of effort, instruction and
      drill. When adults perform mental arithmetic, they activate nonsymbolic,
      approximate number representations, and their performance suffers if this
      nonsymbolic system is impaired. Nonsymbolic number representations also allow
      adults, children, and even infants to add or subtract pairs of dot arrays and to
      compare the resulting sum or difference to a third array, provided that only
      approximate accuracy is required. Here we report that young children, who have
      mastered verbal counting and are on the threshold of arithmetic instruction, can
      build on their nonsymbolic number system to perform symbolic addition and
      subtraction. Children across a broad socio-economic spectrum solved symbolic
      problems involving approximate addition or subtraction of large numbers, both in
      a laboratory test and in a school setting. Aspects of symbolic arithmetic
      therefore lie within the reach of children who have learned no algorithms for
      manipulating numerical symbols. Our findings help to delimit the sources of
      children's difficulties learning symbolic arithmetic, and they suggest ways to
      enhance children's engagement with formal mathematics.

PMID- 17538621
TI  - Universal physical responses to stretch in the living cell.
AB  - With every beat of the heart, inflation of the lung or peristalsis of the gut,
      cell types of diverse function are subjected to substantial stretch. Stretch is a
      potent stimulus for growth, differentiation, migration, remodelling and gene
      expression. Here, we report that in response to transient stretch the
      cytoskeleton fluidizes in such a way as to define a universal response class.
      This finding implicates mechanisms mediated not only by specific signalling
      intermediates, as is usually assumed, but also by non-specific actions of a
      slowly evolving network of physical forces. These results support the idea that
      the cell interior is at once a crowded chemical space and a fragile soft material
      in which the effects of biochemistry, molecular crowding and physical forces are
      complex and inseparable, yet conspire nonetheless to yield remarkably simple
      phenomenological laws. These laws seem to be both universal and primitive, and
      thus comprise a striking intersection between the worlds of cell biology and soft
      matter physics.

PMID- 17538622
TI  - The menthol receptor TRPM8 is the principal detector of environmental cold.
AB  - Sensory nerve fibres can detect changes in temperature over a remarkably wide
      range, a process that has been proposed to involve direct activation of
      thermosensitive excitatory transient receptor potential (TRP) ion channels. One
      such channel--TRP melastatin 8 (TRPM8) or cold and menthol receptor 1 (CMR1)--is
      activated by chemical cooling agents (such as menthol) or when ambient
      temperatures drop below approximately 26 degrees C, suggesting that it mediates
      the detection of cold thermal stimuli by primary afferent sensory neurons.
      However, some studies have questioned the contribution of TRPM8 to cold detection
      or proposed that other excitatory or inhibitory channels are more critical to
      this sensory modality in vivo. Here we show that cultured sensory neurons and
      intact sensory nerve fibres from TRPM8-deficient mice exhibit profoundly
      diminished responses to cold. These animals also show clear behavioural deficits
      in their ability to discriminate between cold and warm surfaces, or to respond to
      evaporative cooling. At the same time, TRPM8 mutant mice are not completely
      insensitive to cold as they avoid contact with surfaces below 10 degrees C,
      albeit with reduced efficiency. Thus, our findings demonstrate an essential and
      predominant role for TRPM8 in thermosensation over a wide range of cold
      temperatures, validating the hypothesis that TRP channels are the principal
      sensors of thermal stimuli in the peripheral nervous system.

PMID- 17538623
TI  - miRNAs control gene expression in the single-cell alga Chlamydomonas reinhardtii.
AB  - MicroRNAs (miRNAs) in eukaryotes guide post-transcriptional regulation by means
      of targeted RNA degradation and translational arrest. They are released by a
      Dicer nuclease as a 21-24-nucleotide RNA duplex from a precursor in which an
      imperfectly matched inverted repeat forms a partly double-stranded region. One of
      the two strands is then recruited by an Argonaute nuclease that is the effector
      protein of the silencing mechanism. Short interfering RNAs (siRNAs), which are
      similar to miRNAs, are also produced by Dicer but the precursors are perfectly
      double-stranded RNA. These siRNAs guide post-transcriptional regulation, as with
      miRNAs, and epigenetic genome modification. Diverse eukaryotes including fungi,
      plants, protozoans and metazoans produce siRNAs but, until now, miRNAs have not
      been described in unicellular organisms and it has been suggested that they
      evolved together with multicellularity in separate plant and animal lineages.
      Here we show that the unicellular alga Chlamydomonas reinhardtii contains miRNAs,
      putative evolutionary precursors of miRNAs and species of siRNAs resembling those
      in higher plants. The common features of miRNAs and siRNAs in an alga and in
      higher plants indicate that complex RNA-silencing systems evolved before
      multicellularity and were a feature of primitive eukaryotic cells.

PMID- 17538625
TI  - A mass spectrometry-friendly database for cSNP identification.

PMID- 17538624
TI  - Gene-specific control of inflammation by TLR-induced chromatin modifications.
AB  - Toll-like receptors (TLRs) induce a multi-component inflammatory response that
      must be tightly regulated to avoid tissue damage. Most known regulatory
      mechanisms target TLR signalling pathways and thus broadly inhibit multiple
      aspects of the inflammatory response. Given the functional diversity of TLR
      induced genes, we proposed that additional, gene-specific regulatory mechanisms
      exist to allow individual aspects of the TLR-induced response to be
      differentially regulated. Using an in vitro system of lipopolysaccharide
      tolerance in murine macrophages, we show that TLR-induced genes fall into two
      categories on the basis of their functions and regulatory requirements. We
      demonstrate that representatives from the two classes acquire distinct patterns
      of TLR-induced chromatin modifications. These gene-specific chromatin
      modifications are associated with transient silencing of one class of genes,
      which includes pro-inflammatory mediators, and priming of the second class, which
      includes antimicrobial effectors. These findings illustrate an adaptive response
      in macrophages and reveal component-specific regulation of inflammation.

PMID- 17538626
TI  - Eris: an automated estimator of protein stability.

PMID- 17538627
TI  - An automated tool for maximum entropy reconstruction of biomolecular NMR spectra.

PMID- 17538628
TI  - Interpreting the unculturable majority.

PMID- 17538629
TI  - Deciphering the combinatorial histone code.

PMID- 17538631
TI  - Spontaneous mutations in the mouse Sharpin gene result in multiorgan
      inflammation, immune system dysregulation and dermatitis.
AB  - Homologues of the SHARPIN (SHANK-associated RH domain-interacting protein) gene
      have been identified in the human, rat and mouse genomes. SHARPIN and its
      homologues are expressed in many tissues. SHARPIN protein forms homodimers and
      associates with SHANK in the post-synaptic density of excitatory
      neurotransmitters in the brain. SHARPIN is hypothesized to have roles in the
      crosslinking of SHANK proteins and in enteric nervous system function. We
      demonstrate that two independently arising spontaneous mutations in the mouse
      Sharpin gene, cpdm and cpdm(Dem), cause a chronic proliferative dermatitis
      phenotype, which is characterized histologically by severe inflammation,
      eosinophilic dermatitis and defects in secondary lymphoid organ development.
      These are the first examples of disease-causing mutations in the Sharpin gene and
      demonstrate the importance of SHARPIN protein in normal immune development and
      control of inflammation.

PMID- 17538632
TI  - Association of PTGDR gene polymorphisms with asthma in two Caucasian populations.
AB  - The prostanoid DP receptor (PTGDR) is shown to be involved in the asthma patho
      physiology and the results from the published genetic association studies are
      inconsistent. Four single nucleotide polymorphisms (SNPs) in PTGDR were genotyped
      in 342 and 294 families from UK and Denmark respectively. Asthma and asthma
      related phenotypes were analyzed using family-based association analyses. In the
      UK families, a promoter polymorphism (-731A/G) showed significant associations
      with asthma (P=0.0022), atopic asthma (P=0.0044), bronchial hyperreactivity or
      BHR (P=0.00120) and strict asthma (P=0.0008). The P-values for asthma, BHR and
      strict asthma were significant even after the most stringent correction for the
      number of markers and the number of phenotypes analyzed (<0.0031). An intronic
      polymorphism (+6651C/T) also showed significant associations with asthma
      (P=0.0302), atopic asthma (P=0.0131), BHR (P=0.0249) and strict asthma
      (P=0.0261). In the Danish families, an intronic polymorphism (+6541C/T) showed
      significant associations with asthma (P=0.0071), atopic asthma (P=0.0348), BHR
      (P=0.0033) and strict asthma (P=0.0381). The results of haplotype analyses
      supported the ones of the single SNP analyses. Thus, we demonstrated significant
      evidence of association between polymorphisms in PTGDR with asthma phenotypes in
      the two Caucasian populations.

PMID- 17538633
TI  - The role of the Toll receptor pathway in susceptibility to inflammatory bowel
      diseases.
AB  - The intestinal flora has long been thought to play a role either in initiating or
      in exacerbating the inflammatory bowel diseases (IBD). Host defenses, such as
      those mediated by the Toll-like receptors (TLR), are critical to the
      host/pathogen interaction and have been implicated in IBD pathophysiology. To
      explore the association of genetic variation in TLR pathways with susceptibility
      to IBD, we performed a replication study and pooled analyses of the putative IBD
      risk alleles in NFKB1 and TLR4, and we performed a haplotype-based screen for
      association to IBD in the TLR genes and a selection of their adaptor and
      signaling molecules. Our genotyping of 1539 cases of IBD and pooled analysis of
      4805 cases of IBD validates the published association of a TLR4 allele with risk
      of IBD (odds ratio (OR): 1.30, 95% confidence interval (CI): 1.15-1.48;
      P=0.00017) and Crohn's disease (OR: 1.33, 95% CI: 1.16-1.54; P=0.000035) but not
      ulcerative colitis. We also describe novel suggestive evidence that TIRAP (OR:
      1.16, 95% CI: 1.04-1.30; P=0.007) has a modest effect on risk of IBD. Our
      analysis, therefore, offers additional evidence that the TLR4 pathway - in this
      case, TLR4 and its signaling molecule TIRAP - plays a role in susceptibility to
      IBD.

PMID- 17538634
TI  - Teaching teamwork during the Neonatal Resuscitation Program: a randomized trial.
AB  - OBJECTIVE: To add a team training and human error curriculum to the Neonatal
      Resuscitation Program (NRP) and measure its effect on teamwork. We hypothesized
      that teams that received the new course would exhibit more teamwork behaviors
      than those in the standard NRP course. STUDY DESIGN: Interns were randomized to
      receive NRP with team training or standard NRP, then video recorded when they
      performed simulated resuscitations at the end of the day-long course. Outcomes
      were assessed by observers blinded to study arm allocation and included the
      frequency or duration of six team behaviors: inquiry, information sharing,
      assertion, evaluation of plans, workload management and vigilance. RESULT: The
      interns in the NRP with team training group exhibited more frequent team
      behaviors (number of episodes per minute (95% CI)) than interns in the control
      group: information sharing 1.06 (0.24, 1.17) vs 0.13 (0.00, 0.43); inquiry 0.35
      (0.11, 0.42) vs 0.09 (0.00, 0.10); assertion 1.80 (1.21, 2.25) vs 0.64 (0.26,
      0.91); and any team behavior 3.34 (2.26, 4.11) vs 1.03 (0.48, 1.30) (P-values
      <0.008 for all comparisons). Vigilance and workload management were practiced
      throughout the entire simulated code by nearly all the teams in the NRP with team
      training group (100% for vigilance and 88% for workload management) vs only 53
      and 20% of the teams in the standard NRP. No difference was detected in the
      frequency of evaluation of plans. CONCLUSION: Compared with the standard NRP, NRP
      with a teamwork and human error curriculum led interns to exhibit more team
      behaviors during simulated resuscitations.

PMID- 17538635
TI  - Positive and negative regulation of adenovirus infection by CAR-like soluble
      protein, CLSP.
AB  - Coxsackievirus and adenovirus receptor (CAR) is a member of the immunoglobulin
      (Ig) superfamily and a component of epithelial tight junction. CAR also functions
      as a primary receptor for coxsackievirus B and adenovirus (Ad) infection. In this
      study, we report the identification of a novel protein, CAR-like soluble protein
      (CLSP), which is closely related to CAR. Mouse CLSP (mCLSP) was composed of 390
      amino acids, including three Ig domains, and showed strong homology to the IgV
      domain of CAR. Interestingly, mCLSP lacks a transmembrane domain, indicating that
      this is a soluble protein. mCLSP mRNA was detected primarily in the brain and
      ovary. When mCLSP cDNA was introduced into SK HEP-1 cells, which were known to be
      CAR positive and easily infected with Ad vector, the infection with Ad vector was
      severely inhibited. On the other hand, mCLSP promoted the infection with Ad
      vector in CAR-negative NIH3T3 cells. Furthermore, recombinant CLSP directly bound
      to Ad and inhibited the Ad vector-mediated transduction in SK HEP-1 cells.
      Computational analysis for a genome database showed that the CLSP gene is rodent
      specific, and that human and bovine lack this gene. These results suggest that
      CLSP may play a role in the antiviral defense of the host in rodent animals.

PMID- 17538636
TI  - The combination of IGF-I and KGF cDNA improves dermal and epidermal regeneration
      by increased VEGF expression and neovascularization.
AB  - Insulin-like growth factor-I (IGF-I) and keratinocyte growth factor (KGF) cDNA
      gene transfer individually improves dermal and epidermal regeneration. The aim of
      the present study was to determine whether the combination of IGF-I plus KGF cDNA
      further improves wound healing and by which mechanisms these changes occur. Rats
      received an acute wound and were divided into four groups to receive weekly
      subcutaneous injections of liposomes plus Lac Z cDNA, liposomes plus IGF-I cDNA,
      liposomes plus KGF cDNA, or liposomes plus IGF-I/KGF cDNA. Planimetry,
      immunological assays, histological and immunohistochemical techniques were used
      to determine IGF-I, KGF, platelet-derived growth factor, fibroblast growth factor
      (FGF), transforming growth factor-beta and vascular endothelial growth factor
      (VEGF) expression and different types of collagen (I, III and IV). IGF-I, KGF and
      their combination cDNA treatment significantly (P<0.05) accelerated re
      epithelization, increased IGF-I, KGF, FGF, VEGF and collagen type IV expression,
      while it had no effect on collagen type I and III expression. The combination of
      IGF-I plus KGF cDNA increased (P<0.05) neovascularization and VEGF expression
      when compared to IGF-I cDNA, KGF cDNA groups and controls. In conclusion,
      exogenous administration of liposomal IGF-I plus KGF cDNA enhanced dermal and
      epidermal regeneration which is due to increased neovascularization.

PMID- 17538637
TI  - An HSV-2-based oncolytic virus deleted in the PK domain of the ICP10 gene is a
      potent inducer of apoptotic death in tumor cells.
AB  - The N-terminus of the ICP10 gene of type 2 herpes simplex virus (HSV-2) encodes a
      serine/threonine protein kinase (PK) domain that facilitates HSV-2 replication by
      activating the Ras/MEK/MAPK mitogenic pathway and suppressing apoptosis. We
      recently demonstrated that deletion of this oncogenic PK domain converts it to a
      potent oncolytic agent. This mutant, which we have designated FusOn-H2,
      preferentially replicates in and thus lyses tumor cells in which the Ras
      signaling pathway is constitutively activated. Here we show that FusOn-H2 exerts
      strong ability in inducing apoptosis in different lines of human tumor cells and
      in esophageal tumors growing in mice. The apoptotic effect produced by FusOn-H2
      was not restricted to infected cells but extended to uninfected bystander cells,
      thereby increasing the lethality of the virus. These results add a novel killing
      mechanism to those previously assigned to FusOn-H2, rendering it an attractive
      candidate for clinical trials.

PMID- 17538638
TI  - The impact of the use of PDE5 inhibitors for erectile dysfunction on the lives of
      Australian men.
AB  - This article presents findings from a recent cross-sectional study that was
      designed to evaluate both the impact of erectile dysfunction (ED) on the lives of
      Australian men, and explore whether the use of PDE5 inhibitors was able to alter
      this impact. The sample comprised 410 men with ED, and 242 men who did not have
      ED. All men were primarily recruited over the internet via men's health web
      sites. Participants completed a questionnaire to assess their self-esteem,
      masculinity, quality of life, sexual satisfaction, relationship satisfaction and
      usage of oral ED medication. The results demonstrated that men with ED
      experienced deficits on all of the psychosocial areas when compared to men
      without ED. Moreover, treatment with ED medication did not alleviate this
      deficit. Implications of these findings for the treatment of men with ED are
      discussed in the context of the biopsychosocial model of health and the need for
      a multidisciplinary approach to ED management is highlighted.

PMID- 17538639
TI  - Transdermal testosterone gel increases serum testosterone levels in hypogonadal
      men in Taiwan with improvements in sexual function.
AB  - A randomized, double-blind, placebo-controlled trial was conducted to (1)
      evaluate efficacy and safety of transdermal testosterone gel (AndroGel) for
      hypogonadal men in Taiwan, and (2) observe improvements in sexual function
      through international index of erectile function (IIEF) scores. Eligible
      hypogonadal men were randomized to receive 50 mg/day transdermal testosterone gel
      (TTG) or placebo for 3 months. Primary end point was change from baseline in
      total testosterone (TT) and free testosterone (FT). Secondary end points were
      change from baseline in serum hormone levels (such as dihydrotestosterone (DHT),
      estradiol (E2), luteinizing hormone (LH), follicle-stimulating hormone (FSH) and
      sex-hormone-binding globulin (SHBG)) and changes in IIEF scores. Safety
      evaluations included adverse events (AEs) and skin irritation assessment.
      Compared with baseline, the TTG group (n=20) had statistically significant
      increases in mean TT levels at month 1 (P=0.024) and month 2 (P=0.025), but no
      significant changes at month 3. TT levels in the placebo group (n=18) showed no
      statistically significant change at any visit. Changes in FT levels paralleled
      changes in TT levels in both groups. TTG group IIEF scores were significantly
      increased at month 3 (P=0.01), compared with a decline in placebo scores. No drug
      related AEs occurred in the TTG group; the placebo group had 2 AEs (mild skin
      rash). In conclusion, TTG effectively restores serum TT and FT levels to a normal
      physiological range for hypogonadal men in Taiwan and improves sexual function.

PMID- 17538640
TI  - The role of hypoxia in erectile dysfunction mechanisms.
AB  - Chronic hypoxia is related to many pathological conditions: aging, heart and
      respiratory failure, sleep apneas, smoke, chronic obstructive pulmonary disease
      (COPD), diabetes, hypertension and arteriosclerosis, all characterized by
      reductions of sleep-related erections (SREs) and by erectile dysfunction (ED).
      Sleep-related erections occur naturally during rapid eye movement (REM) sleep in
      sexually potent men. Hypoxia is also a physiological condition at altitude. The
      level of inspired oxygen decreases progressively with the increase of altitude;
      for this reason, this study was performed to evaluate the relationship of SREs
      with hypoxic environment. SREs have been recorded by an erectometer (RigiScan) on
      three mountain climbers (mean age: 32.5) during a 26-day stay at an altitude
      ranging from 2000 to 5600 m above sea level. Twenty-four records have been made
      at progressively increasing altitudes. A data analysis was carried out on a
      statistical mean of the three values of each variable and an analysis of variance
      (ANOVA) and Newman-Keuls test were carried out for multiple comparison among
      groups. At altitudes over 4450 m, we found lack of rigidity at 80-100% and 60
      79%. Mean % of rigidity and rigidity time of 80-100% (tip and base) decreased
      progressively with altitude. No significant reductions were shown in rigidity
      time at 0-19% and at 20-39% (tip and base), of total number, of total and mean
      duration of SREs. Pathological rigidometric records at high altitude in sexually
      potent men at sea level clarify the primary role of hypoxia in physiopathological
      ED pathway.

PMID- 17538641
TI  - Alcohol consumption and erectile dysfunction: meta-analysis of population-based
      studies.
AB  - Alcohol is long regarded as a risk factor for erectile dysfunction (ED), but
      epidemiological evidence has been equivocal. We aimed to investigate the ED risk
      associated with various levels of alcohol consumption by meta-analysis. We
      searched for population-based studies on ED through Medline, PubMed, PsychInfo,
      and scanned through reference lists. Eleven cross-sectional studies were included
      and analyzed with random effects model. We reviewed the results from one cross
      sectional study and two cohort studies. Regular alcohol consumption was
      negatively associated with ED (odds ratio (OR)=0.79; 99% confidence interval
      (CI), 0.67-0.92; P<0.001). Consumption of 8 or more drinks/week significantly
      reduced the risk of ED (OR=0.85; 99% CI, 0.73-0.99; P=0.007), but consumption of
      less alcohol (1-7 drinks/week) was not significant (OR=0.73; 99% CI, 0.44, 1.20;
      P=0.101). Begg's test and Egger's test detected no significant publication bias.
      Our estimates (in sensitivity analyses) were rendered nonsignificant when
      International Index of Erectile Function definition was used and when statistical
      adjustment was made only for age. Meta-analysis of cross-sectional studies
      yielded a protective association of alcohol on ED, but the two cohort studies did
      not demonstrate any significant findings for alcohol consumption. More research
      is needed to confirm whether alcohol is protective or is unrelated to ED
      development.

PMID- 17538642
TI  - Real-time PCR and enzyme-linked fluorescent assay methods for detecting Shiga
      toxin-producing Escherichia coli in mincemeat samples.
AB  - This work aimed to compare real-time polymerase chain reaction (PCR) with the
      commercially available enzyme-linked fluorescent assay (ELFA) VIDAS ECOLI O157
      for detecting Escherichia coli O157 in mincemeat. In addition, a PCR-based survey
      on Shiga-toxin-producing E. coli (STEC) in mincemeat collected in Italy is
      presented. Real-time PCR assays targeting the stx genes and a specific STEC O157
      sequence (SILO157, a small inserted locus of STEC O157) were tested for their
      sensitivity on spiked mincemeat samples. After overnight enrichment, the presence
      of STEC cells could be clearly determined in the 25 g samples containing 10
      bacterial cells, while the addition of five bacteria provided equivocal PCR
      results with Ct values very close to or above the threshold of 40. The PCR tests
      proved to be more sensitive than the ELFA-VIDAS ECOLI O157, whose detection level
      started from 50 bacterial cells/25 g of mincemeat. The occurrence of STEC in 106
      mincemeat (bovine, veal) samples collected from September to November 2004 at
      five different points of sale in Italy (one point of sale in Arezzo, Tuscany,
      central Italy, two in Mantova, Lombardy, Northern Italy, and two in Bologna,
      Emilia-Romagna, upper-central Italy) was less than 1%. Contamination by the main
      STEC O-serogroups representing a major public health concern, including O26, O91,
      O111, O145, and O157, was not detected. This survey indicates that STEC present
      in these samples are probably not associated with pathogenesis in humans.

PMID- 17538643
TI  - Genomic diversity and relationship of Bacillus thuringiensis and Bacillus cereus
      by multi-REP-PCR fingerprinting.
AB  - The genomic diversity and relationship among 56 Bacillus thuringiensis and
      Bacillus cereus type strains were investigated by multi-REP-PCR fingerprinting
      consisting of three PCR reactions targeting the enterobacterial ERIC1 and ERIC2
      and the streptococcal BOXA1R consensus sequences. A total of 113 polymorphic
      bands were generated in the REP-PCR profiles that allowed tracing of a single
      dendrogram with three major groups. Bacillus cereus strains clustered together in
      the A and B groups. Most of the B. thuringiensis strains clustered in group C,
      which included groups of serovars with a within-group similarity higher than 40%
      as follows: darmstadiensis, israelensis, and morrisoni; aizawai, kenyae,
      pakistani, and thompsoni; canadensis, entomocidus, galleriae, kurstaki, and
      tolworthi; alesti, dendrolimus, and kurstaki; and finitimus, sotto, and
      thuringiensis. Multi-REP-PCR fingerprinting clustered B. thuringiensis serovars
      in agreement with previously developed multilocus sequence typing schemes,
      indicating that it represents a rapid shortcut for addressing the genetic
      relationship of unknown strains with the major known serovars.

PMID- 17538644
TI  - The genetic diversity of rhizobia associated with Dalea purpurea Vent. in
      fragmented grasslands of west-central Minnesota.
AB  - The increase in human population and the spread of agriculture over the past 150
      years have transformed the landscape in west-central Minnesota into a mosaic of
      agricultural fields and urban land, leaving only remnants of the once dominant
      prairie ecosystem. Limited natural habitat in this fragmented landscape threatens
      the diversity and abundance of native legumes and could impact the size and
      function of associated belowground microbial populations. In this study, BOXA1R
      PCR and 16S rRNA gene sequence analyses were used to assess the genetic diversity
      of rhizobia associated with Dalea purpurea (Vent.) in nine prairie remnants
      ranging in size from 0.04 to 3.5 ha. The variation in soil properties was also
      determined. While 53 different genotypes of rhizobia were identified, four of
      these accounted for 84% of the 1029 rhizobia characterized using BOXA1R PCR.
      Representatives from three of the four dominant genotypes had a 16S rRNA gene
      sequence similar to that of Rhizobium gallicum, with two of these genotypes
      recovered at all sites. The fourth genotype was similar to that of Rhizobium etli
      and occurred with frequency at only two sites. Rhizobium genotype richness and
      site area were positively correlated. The implications of these results are
      discussed.

PMID- 17538645
TI  - The phytopathogenic fungi Leptosphaeria maculans and Leptosphaeria biglobosa:
      chemotaxonomical characterization of isolates and metabolite production in
      different culture media.
AB  - Previous molecular chemotaxonomic analyses of isolates of the plant pathogenic
      fungus Leptosphaeria maculans (Desm.) Ces. et de Not. (asexual stage Phoma lingam
      (Tode ex Fr.) Desm.) in a chemically defined medium suggested that this species
      complex was composed of at least three distinct groups. Subsequently, a group
      within L. maculans was classified as Leptosphaeria biglobosa, on the basis of
      morphologic characteristics and the lack of sexual crossing. To obtain
      clarification regarding the metabolite profiles of the various groups or species
      of blackleg fungi, the objectives of this work were (i) to determine the chemical
      structures of metabolites produced by Canadian V isolates and Polish-type
      isolates in potato dextrose broth (PDB) and (ii) to determine the chemotaxonomic
      relationship among French isolates of L. biglobosa and among Canadian W isolates
      and Thlaspi isolates of L. maculans. Here, we report for the first time that
      Canadian V isolates grown in PDB produced 2,4-dihydroxy-3,6-dimethylbenzaldehyde,
      a metabolite never reported from L. maculans, but none of the usual phytotoxins
      (sirodesmins). In addition, we report a new metabolite, 2-[2-(5
      hydroxybenzofuranyl)]-3-(4-hydroxyphenyl)propanenitrile, from Polish-type
      isolates of L. maculans grown in PDB and the metabolite profiles of 16 Thlaspi
      isolates. The metabolite profiles of Thlaspi isolates indicate that these are
      part of two distinct groups, the Polish W group and the Canadian W group, i.e.,
      L. biglobosa. Finally, we demonstrate that the metabolite profiles of the French
      isolates classified as L. biglobosa are similar to those of Canadian W isolates.

PMID- 17538646
TI  - Detection of virulence factors in high-level gentamicin-resistant Enterococcus
      faecalis and Enterococcus faecium isolates from a Tunisian hospital.
AB  - Phenotypic and genotypic determination of virulence factors were carried out in
      46 high-level gentamicin-resistant (HLGR) clinical Enterococcus faecalis (n=34)
      and Enterococcus faecium (n=12) isolates recovered from different patients in La
      Rabta Hospital in Tunis, Tunisia, between 2000 and 2003 (all these isolates
      harboured the aac(6')-aph(2") gene). The genes encoding virulence factors (agg,
      gelE, ace, cylLLS, esp, cpd, and fsrB) were analysed by PCR and sequencing. The
      production of gelatinase and hemolysin, the adherence to caco-2 and hep-2 cells,
      and the capacity for biofilm formation were investigated in all 46 HLGR
      enterococci. The percentages of E. faecalis isolates harbouring virulence genes
      were as follows: gelE, cpd, and ace (100%); fsrB (62%); agg (56%); cylLLS
      (41.2%); and esp (26.5%). The only virulence gene detected among the 12 HLGR E.
      faecium isolates was esp (58%). Gelatinase activity was detected in 22 of the 34
      E. faecalis isolates (65%, most of them with the gelE+-fsrB+ genotype); the
      remaining 12 isolates were gelatinase-negative (with the gelE+-fsrB- genotype and
      the deletion of a 23.9 kb fragment of the fsr locus). Overall, 64% of the cylLLS
      containing E. faecalis isolates showed beta-hemolysis. A high proportion of our
      HLGR E. faecalis isolates, in contrast to E. faecium, showed moderate or strong
      biofilm formation or adherence to caco-2 and hep-2 cells.

PMID- 17538647
TI  - Papaya shoot tip associated endophytic bacteria isolated from in vitro cultures
      and host-endophyte interaction in vitro and in vivo.
AB  - Fourteen distinct bacterial clones were isolated from surface-sterilized shoot
      tips (approximately 1 cm) of papaya (Carica papaya L. 'Surya') planted on
      Murashige and Skoog (MS)-based papaya culture medium (23/50 nos.) during the 2-4
      week period following in vitro culturing. These isolates were ascribed to six
      Gram-negative genera, namely Pantoea (P. ananatis), Enterobacter (E. cloacae),
      Brevundimonas (B. aurantiaca), Sphingomonas, Methylobacterium (M. rhodesianum),
      and Agrobacterium (A. tumefaciens) or two Gram-positive genera, Microbacterium
      (M. esteraromaticum) and Bacillus (B. benzoevorans) based on 16S rDNA sequence
      analysis. Pantoea ananatis was the most frequently isolated organism (70% of the
      cultures) followed by B. benzoevorans (13%), while others were isolated from
      single stocks. Bacteria-harboring in vitro cultures often showed a single
      organism. Pantoea, Enterobacter, and Agrobacterium spp. grew actively on MS-based
      normal papaya medium, while Microbacterium, Brevundimonas, Bacillus,
      Sphingomonas, and Methylobacterium spp. failed to grow in the absence of host
      tissue. Supplying MS medium with tissue extract enhanced the growth of all the
      organisms in a dose-dependent manner, indicating reliance of the endophyte on its
      host. Inoculation of papaya seeds with the endophytes (20 h at OD550=0.5) led to
      delayed germination or slow seedling growth initially. However, the inhibition
      was overcome by 3 months and the seedlings inoculated with Pantoea,
      Microbacterium, or Sphingomonas spp. displayed significantly better root and
      shoot growths.

PMID- 17538648
TI  - Optimization of 6-carboxy-X-rhodamine concentration for real-time polymerase
      chain reaction using molecular beacon chemistry.
AB  - The optimal 6-carboxy-X-rhodamine (ROX) concentration, which is used as a passive
      reference dye for real-time quantitative polymerase chain reaction (PCR) with
      molecular beacon chemistry, was determined with the Mx4000 Multiplex Quantitative
      PCR System. Additionally, the effects of changing ROX concentrations on PCR
      reproducibility, Ct values, and efficiency were investigated with this system by
      using the PCR data obtained from amplification of the Escherichia coli shiga
      toxin 2 (stx2) gene and the Campylobacter jejuni luxS gene. This study indicated
      that different ROX concentrations influence many aspects of the real-time PCR
      reaction. ROX concentration variation could have consequences in the analysis of
      quantitative data and may lead to erroneous results. This study further indicated
      that the optimal ROX concentration is 60 nmol/L for real-time PCR, using
      molecular beacon chemistry for PCR assay of luxS and stx2 genes.

PMID- 17538649
TI  - Detection of the Escherichia coli pathogenic gene eae with three real-time
      polymerase chain reaction methods.
AB  - Several real-time polymerase chain reaction (PCR) methods are currently available
      to rapidly detect the presence of a specific DNA sequence. When used for
      detection of pathogenic organisms, the turnaround time for PCR-based methods is
      much lower than for traditional culture techniques. This study compared the
      sensitivity of three real-time PCR methods when detecting the Escherichia coli
      pathogenic gene eae to determine which method is most effective in identifying
      very low levels of the organism. The three methods were used to detect the eae
      gene over a range of DNA concentrations. The differences in sensitivity were
      statistically significant (p<0.05), and SYBR Green I PCR was found to have the
      lowest detection limit of the three; LUX primers had the highest detection limit.
      Therefore, using a defined DNA concentration for detecting the eae gene, SYBR
      Green I is the best alternative.

PMID- 17538650
TI  - Potential of the volatile-producing fungus Muscodor albus for control of building
      molds.
AB  - The possibility of using the volatile-producing fungus Muscodor albus for
      biofumigation against building molds was investigated. Several species of
      Aspergillus and Penicillium as well as fungi belonging to nine other genera were
      inhibited or killed in vitro by volatiles produced by potato dextrose agar or rye
      grain cultures of M. albus. Trichoderma viride was the only fungus that was not
      inhibited by M. albus volatiles. To test biofumigation as a preventative
      treatment against fungal colonization of building material, dry pieces of gypsum
      drywall were fumigated with grain cultures of M. albus in closed boxes. After a
      simulated water damage and incubation under saturated humidity for 2 weeks,
      untreated drywall developed natural fungal populations of about 10(5)-10(6)
      cfu/cm2, while drywall fumigated with M. albus culture (20 g/11 L) had
      nondetectable fungal populations. To test for curative ability, moist pieces of
      drywall heavily colonized with Cladosporium cladosporioides, Aspergillus niger,
      or Stachybotrys chartarum were fumigated for 48 h with grain cultures of M.
      albus. Cladosporium cladosporioides was eliminated within 48 h, while A. niger
      and S. chartarum were usually more resistant. However, a longer curative
      fumigation of 96 h was effective in reducing A. niger or naturally occurring mold
      populations by about 5 log values. The production of volatile organic compounds
      from 20 g of rye grain culture in 11 L containers was monitored by solid-phase
      micro extraction and gas chromatography. Concentrations of isobutyric acid, the
      most abundant volatile, increased gradually in the headspace until it reached 25
      microg/L (m/v) within 96 h. The second and third most abundant compounds, 2
      methyl-1-butanol and isobutanol, peaked at about 10 and 5 microg/L (m/v),
      respectively, within the first 24 h and declined gradually afterwards.

PMID- 17538651
TI  - Culture of Helicobacter pylori from stool samples in children.
AB  - We evaluated two protocols for isolation of Helicobacter pylori in stool from
      biopsied and nonbiopsied children. Twenty-three child patients whose presumptive
      positivity or negativity was diagnosed by endoscopy and a rapid urease test at
      site were used to compare biopsy-based tests with stool-based tests (H. pylori
      stool antigen test and stool culture). Their gastric activity and bacterial
      density were graded by the updated Sydney system. Biopsy and stool specimens were
      cultured on Campy-blood and Belo horizonte agar plates after enrichment in
      selective Campy-Thio medium. To compare two stool culture protocols, stools from
      20 nonbiopsied children were tested by the HpSA test and cultured either as above
      or after treatment with cholestyramine. Grown colonies were screened by Gram
      staining, slide agglutination using anti-H. pylori monoclonal IgG; positive
      isolates were tested by biochemical tests and polymerase chain reaction for H.
      pylori-specific ureA gene. Coccoid H. pylori was isolated in stool samples from
      the biopsied patients whose bacterial density was two to four in histology. Their
      oxidase was slightly positive but became positive after two subcultures, while
      additional biochemical tests confirmed the isolation of H. pylori. Similar
      coccoid but oxidase positive H. pylori was isolated from three nonbiopsied
      children with the protocol of cholestyramine treatment only. The density of
      bacteria in the stomach may influence the recovery of H. pylori from stool;
      inactivation of bile with cholestyramine improves the yield in culture and favors
      isolation of an enhanced metabolic form of bacteria.

PMID- 17538652
TI  - Comparison of transformation protocols in Streptococcus gordonii and evaluation
      of native promoter strength using a multiple-copy plasmid.
AB  - An active area of research in the development of Streptococcus gordonii for use
      as a bacterial commensal vector involves the identification and utilization of
      strong promoters for high-level expression of heterologous products. Escherichia
      coli plasmid vectors containing different streptococcal promoters often fail to
      become established in E. coli for unknown reasons. Therefore, it is desirable at
      times to transform S. gordonii, which is naturally competent, with small
      quantities of nascently ligated DNA without using E. coli first to amplify or
      screen the product. By comparing the efficiency of two methods used to induce
      competence in S. gordonii, it was shown that the use of a synthetic competence
      stimulating peptide substantially enhanced plasmid uptake by S. gordonii. We
      amplified the amylase-binding protein (abpA) promoter from the S. gordonii genome
      and, using a synthetic peptide to induce competence, directly introduced plasmid
      DNA containing this promoter into S. gordonii as an unamplified product of
      ligation. This plasmid facilitated abundant secretion of a heterologous product
      by S. gordonii. By assessing the levels of heterologous product secreted by two
      plasmid constructs, it was possible to evaluate the relative strength of two
      native promoters.

PMID- 17538653
TI  - Phenotypic and molecular characterization of chickpea rhizobia isolated from
      different areas of Tunisia.
AB  - Several phenotypic markers were used in this study to determine the biodiversity
      of rhizobial strains nodulating Cicer arietinum L. in various areas of Tunisia.
      They include symbiotic traits, the use of 21 biochemical substrates, and
      tolerance to salinity and pH. In addition, restriction fragment length
      polymorphisms (RFLPs) of PCR-amplified 16S rDNA were compared with those of
      reference strains. Numeric analysis of the phenotypic characteristics showed that
      the 48 strains studied fell into three distinct groups. This heterogeneity was
      highly supported by the RFLP analysis of 16S rRNA genes, and two ribotypes were
      identified. Chickpea rhizobia isolated from Tunisian soils are both
      phenotypically and genetically diverse. Results showed that 40 and 8 isolates
      were assigned, respectively, to Mesorhizobium ciceri and Mesorhizobium
      mediterraneum.

PMID- 17538654
TI  - Surface motility of Xylella fastidiosa visualized by oblique illumination.
AB  - Stereomicroscopic observations using oblique illuminations revealed the presence
      of two types of movement trails by Xylella fastidiosa strains (A- and G
      genotypes) isolated from almond-leaf scorch samples on the surface of PW and PD3
      culture media. The A-genotype strains showed curved motility trails, and the G
      genotype strains showed straight motility trails. Haloes were found around some G
      genotype colonies due to the excretion of unknown factors and (or) compounds,
      which might be related to bacterial surface motility.

PMID- 17538655
TI  - Assessment of the genetic diversity of Frankia microsymbionts of Elaeagnus
      angustifolia L. plants growing in a Tunisian date-palm oasis by analysis of PCR
      amplified nifD-K intergenic spacer.
AB  - Diversity of Frankia microsymbionts of non-native Elaeagnus angustifolia L.
      plants spontaneously growing in a Tunisian desertic retreat area, the date-palm
      oasis of Tozeur, was investigated by polymerase chain reaction-restriction
      fragment length polymorphism (PCR-RFLP) and PCR-sequencing techniques targeting
      the nifD-K intergenic spacer. Three PCR-RFLP haplotypes (I, II, and III) were
      detected among collected nodules. Haplotype I was detected at all five sampling
      sites and dominated the other haplotypes present at these sites. This haplotype
      was also exhibited by strain BMG5.10, which was isolated by a plant-capturing
      assay in 1998 from soil collected in the same locality, qualifying it to be the
      most competitive haplotype in the edapho-climatic condition of the studied
      desertic date-palm oasis. nifD-K sequences of the three haplotypes formed a
      closely related phylogenetic subgroup. These results suggest that Frankia
      variability is constrained by severe edapho-climatic conditions of retreated
      desert in Tunisian area.

PMID- 17538656
TI  - Sequence variability in the FUM1 gene of Fusarium verticillioides strains.
AB  - Fumonisins are mycotoxins, produced mainly by Fusarium verticillioides, that are
      potentially carcinogenic to humans and toxic to animals. Synthesis of these
      toxins is directed by a cluster of 15 genes, among which FUM1 is the largest; it
      encodes a polyketide synthase. This enzyme probably catalyzes the synthesis of a
      polyketide that forms a large portion of the fumonisin structure. In this study,
      27 strains possessing the FUM1 gene, as determined by polymerase chain reaction,
      were analyzed. A portion of the FUM1 gene was amplified and sequenced from 6 of
      27 Brazilian strains isolated from corn and sorghum. The sequence similarity for
      the six F. verticillioides strains was almost 100%.

PMID- 17538657
TI  - In situ evidence for microdomains in the polymer matrix of bacterial
      microcolonies.
AB  - Confocal laser scanning microscopy and fluorescent lectin-binding analyses (FLBA)
      were used to study the form, arrangement, and composition of exopolymeric
      substances (EPS) surrounding naturally occurring microcolonies in biofilms. FLBA,
      using multiple lectin staining and multichannel imaging, indicated that the EPS
      of many microcolonies exhibit distinct multiple binding regions. A common pattern
      in the microcolonies is a three zone arrangement with cell-associated,
      intercellular, and an outer layer of EPS covering the exterior of the colony.
      Differential binding of lectins suggests that there are differences in the
      glycoconjugate composition or their arrangement in the EPS of microcolonies. The
      combination of FLBA with fluorescent in situ hybridization (FISH) indicates that
      the colonies consist of the major groups, alpha- and beta-Proteobacteria. It is
      suggested that the EPS arrangement observed provides a physical structuring
      mechanism that can segregate extracellular activities at the microscale.

PMID- 17538658
TI  - Temporal expression of Mycobacterium smegmatis respiratory terminal oxidases.
AB  - Terminal oxidases provide the final step in aerobic respiration by reducing
      oxygen. The mycobacteria possess two terminal oxidases: a cytochrome c aa3 type
      and a quinol bd type. We previously isolated a bd-type oxidase knockout mutant of
      Mycobacterium smegmatis that allowed for functional analysis of the aa3 type
      without the contribution of bd-type activity. Growth of M. smegmatis LR222 and
      JAM1 (LR222bd::kan) was monitored and the cytochrome content at different time
      points examined. No difference in aerobic growth was observed between M.
      smegmatis LR222 and JAM1. Membranes were obtained from these cultures and the
      oxidase concentrations were calculated from their spectrum. Although the mutant
      was producing only one oxidase type, this oxidase did not reach wild-type levels
      of expression, suggesting an additional mechanism for energizing the membrane.
      Moreover, the concentration of both oxidases in the wild-type strain dropped when
      cultures entered stationary phase, which was not the case for the aa3-type
      oxidase of the mutant strain. This oxidase remained at a constant concentration
      post mid-log phase. RNase protection assays also demonstrated late growth phase
      dependent message expression of the bd oxidase and that the subunits I and II
      genes were cotranscribed as an operon.

PMID- 17538659
TI  - Talbot effect with rough reflection gratings.
AB  - The Talbot effect is analyzed when steel tape gratings are used. These gratings
      are made on a steel substrate, and, because of the manufacture process, both
      levels of the grating are rough with different roughness parameters. A
      theoretical analysis based on Fresnel regime, which considers the statistical
      properties of roughness, is developed. Analytical formulas that show a decreasing
      exponential dependence on the intensity in terms of the distance between the
      grating and the observation plane are obtained, and an experimental verification
      is also performed.

PMID- 17538660
TI  - Optimum parallel-face slanted surface-relief gratings.
AB  - Using a combination of rigorous coupled-wave analysis and simulated annealing,
      parallel-face slanted surface-relief gratings (PFSSRGs) are optimized. For
      substrate-mode optical interconnects, profiles are presented for both polymer and
      silicon PFSSRGs for both TE and TM polarizations at normal incidence with grating
      periods designed to give a 45 degrees output angle in the negative-first forward
      diffracted order. The resulting diffraction efficiencies range from 70% to 99%,
      with a majority of the optimized profiles yielding over 90%. Optimized polymer
      profiles for TE and TM polarizations exhibit similar high diffraction
      efficiencies, but the TM profiles generally require greater groove depths.
      Silicon profiles optimized for TM polarization have greater diffraction
      efficiencies than those for TE polarization. Profiles that can feasibly be
      fabricated are identified, and sensitivities to groove depth, filling factor,
      slant angle, and incident angle are shown to be modest.

PMID- 17538661
TI  - Extrinsic Fabry-Perot cavity optical fiber liquid-level sensor.
AB  - An optical fiber liquid-level sensor based on an extrinsic Fabry-Perot (FP)
      cavity is proposed and demonstrated. The FP cavity consists of the end of the
      single-mode optical fiber and the elastic silicon layer. Liquid pressures act on
      the mechanical construction to change the cavity length, resulting in
      differential phase shifts that may be observed as variations of the output signal
      intensity. Self-compensated steps have been taken to obtain high accuracy and
      long-term stability in realistic circumstances. Experimental results indicate
      that accuracy of 2 mm over a full scale of 3.5 m (water) is obtained under
      ambient temperature 10-38 degrees C. The sensor can be used to measure liquid
      levels continuously and accurately in explosive and flammable environments.

PMID- 17538662
TI  - Characterization of tunable photonic crystal fiber directional couplers.
AB  - We present a tunable photonic crystal fiber (PCF) directional coupler fabricated
      by a side-polishing method. The PCF directional coupler was modeled as a typical
      single-mode fiber-based directional coupler and analyzed using the improved
      effective-index method (IEIM). The characteristics of the PCF directional coupler
      such as the coupling coefficient and the coupling ratio were measured and found
      to be in good agreement with those predicted by the theoretical model. The PCF
      directional coupler exhibited an insertion loss of approximately 2 dB for a 3 dB
      coupler and was able to tune the coupling ratio between 0% and 100% by tilting
      the angle of the top side-polished quartz block against the fixed-bottom quartz
      block.

PMID- 17538663
TI  - Axial superresolution of two-photon microfabrication.
AB  - An axial superresolution diffraction theory is developed in a two-photon
      microfabrication system. This method can improve the axial superresolution of the
      two-photon microfabrication system. A theoretical analysis of the photosensitive
      resin is discussed based on the exciting power and the concentration of free
      radical theory. Simulated results of the two-photon microfabrication verify the
      method and show that it can provide insight into the microfabrication system.

PMID- 17538664
TI  - Degradation of an image by Gaussian longitudinal motion.
AB  - The effect of random longitudinal motion of an image is discussed. Numerical
      results are given for systems with circular and annular pupils. It is shown that,
      for a given value of the image motion, the time-averaged Strehl ratio is larger
      for a larger value of the obscuration ratio of an annular pupil. We also show
      that the time-averaged image irradiance distribution near its center and the
      corresponding encircled power can be obtained from their aberration-free values
      by multiplying them by the Strehl ratio.

PMID- 17538665
TI  - Broadband antihole photon sieve telescope.
AB  - A broadband-corrected optical telescope has been constructed from a photon sieve
      with five million holes. Through careful optimization of hole size, this
      "antihole" sieve has holes centered on the dark underlying Fresnel zones. The
      diffraction-limited performance of a 1 m focal-length, f/10 element is
      demonstrated with a view toward constructing large lightweight telescopes for
      space applications.

PMID- 17538666
TI  - Speckle correlation method used to measure object's in-plane velocity.
AB  - We present a measurement of an object's in-plane velocity in one direction by the
      use of the speckle correlation method. Numerical correlations of speckle patterns
      recorded periodically during motion of the object under investigation give
      information used to evaluate the object's in-plane velocity. The proposed optical
      setup uses a detection plane in the image field and enables one to detect the
      object's velocity within the interval (10-150) microm x s(-1). Simulation
      analysis shows a way of controlling the measuring range. The presented theory,
      simulation analysis, and setup are verified through an experiment of measurement
      of the velocity profile of an object.

PMID- 17538667
TI  - Discontinuous free-form lens design for prescribed irradiance.
AB  - For the problem of point source forming prescribed irradiance, a new, to the best
      of our knowledge, method-variable separation mapping method is presented, which
      establishes separately the correspondence between variables on the light source
      and the target plane. The role played by the optical surfaces is then to redirect
      the light rays to their corresponding target points. The surface of the lens is
      determined by first calculating the surface points and then their normal vectors.
      Considering that normal deviations are produced in the surface construction
      process, a normal deviation control method is also presented to restrict the
      deviation. With this normal deviation control method, discontinuities are
      introduced onto the lens surface. From these mapping and normal control methods,
      a fast and efficient algorithm has been developed for several prescribed
      irradiance problems with simple nonrotational shape of the illuminated region.

PMID- 17538668
TI  - Reprogrammable optical phase array.
AB  - A novel reprogrammable optical phase array (ROPA) device is presented as a
      reconfigurable electro-optic element. One specific application of the ROPA, a 1 x
      6 electro-optic space switch, is fully described. Switching angles are within 2
      degrees , and switching is achieved through a complementary metal-oxide
      semiconductor (CMOS) controlled, diffraction based, optical phase array in a bulk
      BaTiO3 crystal. The crystal is flip-chipped to the CMOS chip, creating a compact
      fully integrated device. The design, optical simulation, and fabrication of the
      device are described, and preliminary experimental results are presented.

PMID- 17538669
TI  - Estimation of complex refractive index of polydisperse particulate systems from
      multiple-scattered ultraviolet-visible-near-infrared measurements.
AB  - A method to extract the complex refractive index of spherical particles from a
      polydisperse suspension at concentrations where multiple light-scattering effects
      are significant is presented. The optical constants are estimated from total
      diffuse reflectance and transmittance measurements and inverting the measurements
      using the radiative transfer equation (RTE) and the Mie theory for scattering by
      polydisperse spherical particles. The method is tested by applying it to three
      different polydisperse polystyrene suspensions and extracting the optical
      constants of polystyrene particles in the wavelength range of 450-1200 nm. The
      effect of particle size, concentration, and polydispersity on the estimated
      values of the optical constants is also discussed.

PMID- 17538670
TI  - Sub-diffraction-limited multilayer coatings for the 0.3 numerical aperture micro
      exposure tool for extreme ultraviolet lithography.
AB  - Multilayer coating results are discussed for the primary and secondary mirrors of
      the micro-exposure tool (MET): a 0.30 NA lithographic imaging system with a 200
      microm x 600 microm field of view at the wafer plane, operating in the extreme
      ultraviolet (EUV) region at an illumination wavelength around 13.4 nm. Mo/Si
      multilayers were deposited by DC-magnetron sputtering on large-area, curved MET
      camera substrates. A velocity modulation technique was implemented to
      consistently achieve multilayer thickness profiles with added figure errors below
      0.1 nm rms demonstrating sub-diffraction-limited performance, as defined by the
      classical diffraction limit of Rayleigh (0.25 waves peak to valley) or Marechal
      (0.07 waves rms). This work is an experimental demonstration of sub-diffraction-
      limited multilayer coatings for high-NA EUV imaging systems, which resulted in
      the highest resolution microfield EUV images to date.

PMID- 17538671
TI  - Simultaneous transmission for an encrypted image and a double random-phase
      encryption key.
AB  - We propose a method to simultaneously transmit double random-phase encryption key
      and an encrypted image by making use of the fact that an acceptable decryption
      result can be obtained when only partial data of the encrypted image have been
      taken in the decryption process. First, the original image data are encoded as an
      encrypted image by a double random-phase encryption technique. Second, a double
      random-phase encryption key is encoded as an encoded key by the Rivest-Shamir
      Adelman (RSA) public-key encryption algorithm. Then the amplitude of the
      encrypted image is modulated by the encoded key to form what we call an encoded
      image. Finally, the encoded image that carries both the encrypted image and the
      encoded key is delivered to the receiver. Based on such a method, the receiver
      can have an acceptable result and secure transmission can be guaranteed by the
      RSA cipher system.

PMID- 17538672
TI  - Improving photon count and flat profiles of multiplex imaging systems with the
      odd-symmetric quadratic phase modulation mask.
AB  - The odd-symmetric quadratic (OSQ) phase mask is examined as a candidate for
      reduction of working distance and enhancement of light collection in multiplex
      imaging systems. The knowledge gained from the exact mathematical representation
      of the optical transfer function of the OSQ phase mask imager is exploited to
      explain the limits of system performance and quantify the upper bound on the
      magnitude of defocus within which this wavefront coding imager can successfully
      operate. The sensitivity of this imaging system to defocus about the special
      imaging condition that yields an enhanced dynamic range is examined, and it is
      shown that the modulation transfer function (MTF) degradation when the magnitude
      of misfocus is increased past this condition is much more gradual than the
      degradation of a conventional imager past a zero-misfocus state. The condition
      required for the spatial frequency and angular resolution of this OSQ phase mask
      imager to exceed that of its counterpart scaled imager is established, and
      results of simulated imaging under a reduced working distance configuration are
      presented.

PMID- 17538673
TI  - Depth-enhanced integral imaging display system with electrically variable image
      planes using polymer-dispersed liquid-crystal layers.
AB  - A depth-enhanced three-dimensional integral imaging system with electrically
      variable image planes is proposed. For implementing the variable image planes,
      polymer-dispersed liquid-crystal (PDLC) films and a projector are adopted as a
      new display system in the integral imaging. Since the transparencies of PDLC
      films are electrically controllable, we can make each film diffuse the projected
      light successively with a different depth from the lens array. As a result, the
      proposed method enables control of the location of image planes electrically and
      enhances the depth. The principle of the proposed method is described, and
      experimental results are also presented.

PMID- 17538674
TI  - Unexpected irreversible damage of an asymmetric bismuth silicate photorefractive
      spatial light modulator.
AB  - Unexpected irreversible damage occurred repeatedly in the asymmetric bismuth
      silicate (BSO) photorefractive spatial light modulator under some operation
      modes, even though the power of the write-light beam does not exceed the optical
      damage threshold. According to the microscopic surface images and the Raman
      spectra of the BSO film, sudden rising of temperature in local areas caused by
      the drift of the photon-induced electrons is responsible for the damage; the
      damage exists not only on the surface but also inside the BSO crystal. The damage
      is relative to the structure of the spatial light modulator, the operation mode,
      and the growth of the BSO crystal. The information provided by the damage is
      useful for optimizing the structure, the operation modes, and the performance of
      the photorefractive spatial light modulators.

PMID- 17538675
TI  - Fade statistics and aperture averaging for Gaussian beam waves in moderate-to
      strong turbulence.
AB  - The performance of lasercom systems operating in the atmosphere is reduced by
      optical turbulence, which causes irradiance fluctuations in the received signal.
      The result is a randomly fading signal. Fade statistics obtained from
      experimental data were compared to theoretical predictions based on the lognormal
      and gamma-gamma distributions. The probability of fade, the expected number of
      fades per second, and the mean fade time were calculated from the irradiance
      fluctuations of a Gaussian beam wave propagating through the atmosphere along a
      horizontal path, near ground, in the moderate-to-strong optical turbulence
      regime. Irradiance data were collected simultaneously at three receiving
      apertures, each with a different size. Atmospheric propagation parameters were
      inferred from the measurements and were used in calculations for the theoretical
      distributions. It was found that fade predictions made by the gamma-gamma and
      lognormal distributions provide an upper and lower bound, respectively, for the
      probability of fade and the number of fades per second for the irradiance data
      collected in the moderate-to-strong fluctuation regime. What is believed to be a
      new integral expression for the expected number of fades based on the gamma-gamma
      distribution was developed. This new expression tracked the gamma-gamma
      distributed data more closely than the existing approximation and resulted in a
      higher number of fades.

PMID- 17538676
TI  - Statistical analysis of absorption spectra of phytoplankton and of pigment
      concentrations observed during three POMME cruises using a neural network
      clustering method.
AB  - We present a neural network methodology for clustering large data sets into
      pertinent groups. We applied this methodology to analyze the phytoplankton
      absorption spectra data gathered by the Laboratoire d'Oceanographie de
      Villefranche. We first partitioned the data into 100 classes by means of a self
      organizing map (SOM) and then we clustered these classes into 6 significant
      groups. We focused our analysis on three POMME campaigns. We were able to
      interpret the absorption spectra of the samples taken in the first oceanic
      optical layer during these campaigns, in terms of seasonal variability. We showed
      that spectra from the PROSOPE Mediterranean campaign, which was conducted in a
      different region, were strongly similar to those of the POMME-3 campaign. This
      analysis led us to propose regional empirical relationships, linking
      phytoplankton absorption spectra to pigment concentrations, that perform better
      than the previously derived overall relation.

PMID- 17538677
TI  - Smart value-added fiber-optic modules using spatially multiplexed processing.
AB  - Intelligent fiber-optic value-added modules (VAMs) are proposed using what we
      believe to be a novel spatially multiplexed processing technique implemented with
      both reconfigurable and nonreconfigurable predesigned pixels per impinging beam
      that enables desired optical power split states needed for realizing a two state
      reconfigurable VAM. The preferred design uses broadband micromirrors such as ones
      fabricated via optical microelectromechanical systems technology. The basic VAM
      design uses two broadband micromirror pixels, where each pixel has its specific
      location and area and only one of these pixels is electrically driven to adjust
      its small tilt angle. The areas of the pixels are chosen to obtain the desired
      tap power. A proof-of-concept VAM with 100% digital repeatability is demonstrated
      using a Texas Instruments Digital Micromirror Device (DMD) where several
      micromirrors per beam are used to produce the dual-pixel effect. Example tap
      ratios experimentally implemented at 1550 nm include 10:90, 20:80, 66.66:33.33,
      50:50, 30:70, and 25:75. DMD multipixel diffraction limits output port optical
      losses to 3.2 and 3.6 dB. The proposed VAM can have an impact in both digital
      electronic and analog RF optically implemented systems.

PMID- 17538678
TI  - Measurement of the refractive index of distilled water from the near-infrared
      region to the ultraviolet region.
AB  - By the minimum deviation method using a prism shaped cell, the absolute
      refractive indices of high-performance liquid chromatography distilled water were
      measured at the wavelengths from 1129 to 182 nm, at the temperature of 19 degrees
      C, 21.5 degrees C, and 24 degrees C, and then dn/dt at 21.5 degrees C was
      calculated. The coefficients of the four-term Sellmeier dispersion formula were
      determined by using the refractive indices at each temperature. As a result of
      the comparison of our refractive index data in the visible wavelength region with
      the formula by Tilton et al. at the National Bureau of Standards in 1938, both
      the refractive index data corresponded within 6 x 10(-6). In the UV region, the
      absolute refractive index at 193.39 nm calculated by the data measured nearby the
      wavelengths from 200 to 190 nm was 1.436517 (21.5 degrees C). The value was lower
      by 9 x 10(-5) or 10 x 10(-5) than the data measured by Burnett et al. at the
      National Institute of Standards and Technology.

PMID- 17538679
TI  - Interferometry based technique for intensity profile measurements of far IR
      beams.
AB  - We present a novel, to the best of our knowledge, method for measuring the
      intensity profile of far-IR beams. The method is based on the measurements of
      nonstationary variation in optical thickness of a fused-silica plate heated by
      the studied radiation. The optical thickness is observed by means of a reflecting
      interferometer. Purpose-made experimental setup allows one to measure beams with
      an aperture of up to 60 mm with a spatial resolution of 1 mm. The accessibility
      of the utilized technologies and the possibility to easily increase the aperture
      are the major advantages of this approach. The probable area of application for
      the method is measurements of beams produced by powerful industrial far-IR
      lasers.

PMID- 17538680
TI  - Characteristics of a high-power broad-area laser operating in a passively
      stabilized external cavity.
AB  - We narrowed the spectral bandwidth of our 2 W broad-area laser to 8+/-1 GHz with
      a coarse tunability of 12 nm centered near 790 nm in an external cavity. Our
      passively stabilized external cavity was designed for use with high-power
      semiconductor lasers. The cavity length and mount are modular with a fixed pivot
      point so that the optical elements can be changed to access a broad frequency
      spectrum and enable multiple applications. The bandwidth was observed to be
      dependent on the multimode transverse structure of the laser.

PMID- 17538681
TI  - Amplified spontaneous emission in polymer films doped with a perylenediimide
      derivative.
AB  - The presence of amplified spontaneous emission (ASE) by optical pump in
      polystyrene films doped with N,N'-di(10-nonadecyl)perylene-3,4:9,10
      tetracarboxylic diimide (PDI-N) in a range of PDI-N concentrations between 0.25
      and 5 wt. % is reported. Gain coefficients up to 10 cm(-1), at a pump intensity
      of 74 kW/cm2, were obtained. The lowest thresholds (approximately 15 kW/cm2) and
      largest photostabilities measured at 50% (approximately 50 min, i.e., 30,000 pump
      pulses) were obtained for concentrations up to 1 wt. %. The observation of an
      increase in the ASE threshold and a decrease in the photostability for larger
      concentrations is attributed to the presence of aggregated species.

PMID- 17538682
TI  - Theoretical time-domain study of self-imaging properties in a multimode
      interference coupler.
AB  - We report a theoretical and numerical study of self-imaging properties, including
      time domain and pulse spreading, caused by modal group-delay dispersion in
      generalized N x N multimode interference devices achieved by using a mode
      propagation analysis and finite-difference time-domain method. It was found that
      the spatial self-imaging condition does not realize temporal self-imaging but
      lets waveforms separate whose shape depends on input position and input field
      distribution. Pulse spreading, which is sensitive to beam diameter, has a very
      large variation (420 fs) among input positions as well as rising to a very high
      900 fs in response to a 21 fs and spatially Gaussian pulse for the conveniently
      smallest size with 10 channels.

PMID- 17538683
TI  - High-extinction-ratio resonant cavity polarizer for quantum-optics measurements.
AB  - The use of a high-finesse Fabry-Perot ring cavity with an odd number of
      reflections as a high-extinction-ratio resonant polarizer is shown. Experimental
      results from quantum-noise measurements using resonant cavities as spatial and
      spectral filters and precision polarizers are presented.

PMID- 17538684
TI  - Optically based technique for producing merged spectra of water-leaving radiances
      from ocean color remote sensing.
AB  - An optically based technique is presented that produces merged spectra of
      normalized water-leaving radiances L(WN) by combining spectral data provided by
      independent satellite ocean color missions. The assessment of the merging
      technique is based on a four-year field data series collected by an autonomous
      above-water radiometer located on the Acqua Alta Oceanographic Tower in the
      Adriatic Sea. The uncertainties associated with the merged L(WN) obtained from
      the Sea-viewing Wide Field-of-view Sensor and the Moderate Resolution Imaging
      Spectroradiometer are consistent with the validation statistics of the individual
      sensor products. The merging including the third mission Medium Resolution
      Imaging Spectrometer is also addressed for a reduced ensemble of matchups.

PMID- 17538685
TI  - Demonstration of complex-conjugate-resolved harmonic Fourier-domain optical
      coherence tomography imaging of biological samples.
AB  - Complex-conjugate-resolved Fourier-domain optical coherence tomography, where the
      quadrature components of the interferogram are obtained by simultaneous
      acquisition of the first and second harmonics of the phase-modulated
      interferogram, is applied to multisurface test targets and biological samples.
      The method provides efficient suppression of the complex-conjugate, dc, and
      autocorrelation artifacts. A complex-conjugate rejection ratio as high as 70 dB
      is achieved.

PMID- 17538686
TI  - Characterization of a commercialized SERS-active substrate and its application to
      the identification of intact Bacillus endospores.
AB  - Surface-enhanced-Raman-spectroscopy (SERS) can be made an attractive approach for
      the identification of Raman-active compounds and biological materials (i.e.,
      toxins, viruses, or intact bacterial cells or spores) through development of
      reproducible, spatially uniform SERS-active substrates. Recently, reproducible
      (from substrate to substrate), spatially homogeneous (over large areas) SERS
      active substrates have been commercialized and are now available in the
      marketplace. Scanning electron microscopy and high-resolution, tapping-mode
      atomic force microscopy have been used to analyze these novel plasmonic surfaces
      for topographical consistency. Additionally, we have assessed, by wavelength
      tunable microreflectance spectrometry, the spatial distribution of the localized
      surface plasmon resonance (LSPR) across a single substrate surface as well as the
      LSPR lambda(MAX) variance from substrate to substrate. These analyses reveal that
      these surfaces are topologically uniform with small LSPR variance from substrate
      to substrate. Further, we have utilized these patterned surfaces to acquire SERS
      spectral signatures of four intact, genetically distinct Bacillus spore species
      cultivated under identical growth conditions. Salient spectral signature features
      make it possible to discriminate among these genetically distinct spores.
      Additionally, partial least squares, a multivariate calibration method, has been
      used to develop personal-computer-borne algorithms useful for classification of
      unknown spore samples based solely on SERS spectral signatures. To our knowledge,
      this is the first report detailing application of these commercially available
      SERS-active substrates to identification of intact Bacillus spores.

PMID- 17538687
TI  - Frequency of cancer genes on the chicken z chromosome and its human homologues:
      implications for sex chromosome evolution.
AB  - It has been suggested that there are special evolutionary forces that act on sex
      chromosomes. Hemizygosity of the X chromosome in male mammals has led to
      selection for male-advantage genes, and against genes posing extreme risks of
      tumor development. A similar bias against cancer genes should also apply to the Z
      chromosome that is present as a single copy in female birds. Using comparative
      database analysis, we found that there was no significant underrepresentation of
      cancer genes on the chicken Z, nor on the Z-orthologous regions of human
      chromosomes 5 and 9. This result does not support the hypothesis that genes
      involved in cancer are selected against on the sex chromosomes.

PMID- 17538688
TI  - Identification and analysis of novel amino-acid sequence repeats in Bacillus
      anthracis str. Ames proteome using computational tools.
AB  - We have identified four repeats and ten domains that are novel in proteins
      encoded by the Bacillus anthracis str. Ames proteome using automated in silico
      methods. A "repeat" corresponds to a region comprising less than 55-amino-acid
      residues that occur more than once in the protein sequence and sometimes present
      in tandem. A "domain" corresponds to a conserved region with greater than 55
      amino-acid residues and may be present as single or multiple copies in the
      protein sequence. These correspond to (1) 57-amino-acid-residue PxV domain, (2)
      122-amino-acid-residue FxF domain, (3) 111-amino-acid-residue YEFF domain, (4)
      109-amino-acid-residue IMxxH domain, (5) 103-amino-acid-residue VxxT domain, (6)
      84-amino-acid-residue ExW domain, (7) 104-amino-acid-residue NTGFIG domain, (8)
      36-amino-acid-residue NxGK repeat, (9) 95-amino-acid-residue VYV domain, (10) 75
      amino-acid-residue KEWE domain, (11) 59-amino-acid-residue AFL domain, (12) 53
      amino-acid-residue RIDVK repeat, (13) (a) 41-amino-acid-residue AGQF repeat and
      (b) 42-amino-acid-residue GSAL repeat. A repeat or domain type is characterized
      by specific conserved sequence motifs. We discuss the presence of these repeats
      and domains in proteins from other genomes and their probable secondary
      structure.

PMID- 17538689
TI  - Protein interactions from complexes: a structural perspective.
AB  - By combining crystallographic information with protein-interaction data obtained
      through traditional experimental means, this paper determines the most
      appropriate method for generating protein-interaction networks that incorporate
      data derived from protein complexes. We propose that a combined method should be
      considered; in which complexes composed of five chains or less are decomposed
      using the matrix model, whereas the spoke model is used to derive pairwise
      interactions for those with six chains or more. The results presented here should
      improve the accuracy and relevance of studies investigating the topology of
      protein-interaction networks.

PMID- 17538690
TI  - Protein coevolution and isoexpression in yeast macromolecular complexes.
AB  - Previous studies in the yeast Saccharomyces cerevisiae have shown that genes
      encoding subunits of macromolecular complexes have similar evolutionary rates (K)
      and expression levels (E). Besides, it is known that the expression of a gene is
      a strong predictor of its rate of evolution (i.e., E and K are correlated). Here
      we show that intracomplex variation of subunit expression correlates with
      intracomplex variation of their evolutionary rates (using two different measures
      of dispersion). However, a similar trend was observed for randomized complexes.
      Therefore, using a mathematical transformation, we created new variables
      capturing intracomplex variation of both E and K. The values of these new
      compound variables were smaller for real complexes than for randomized ones. This
      shows that proteins in complexes tend to have closer expressivities (E) and K's
      simultaneously than in the randomly grouped genes. We speculate about the
      possible implications of this finding.

PMID- 17538691
TI  - Normalisation of multicondition cDNA macroarray data.
AB  - Background. Normalisation is a critical step in obtaining meaningful information
      from the high-dimensional DNA array data. This is particularly important when
      complex biological hypotheses/questions, such a functional analysis and
      regulatory interactions within biological systems, are investigated. A
      nonparametric, intensity-dependent normalisation method based on global
      identification of self-consistent set (SCS) of genes is proposed here for such
      systems. Results. The SCS normalisation is introduced and its behaviour
      demonstrated for a range of user-defined parameters affecting its performance. It
      is compared to a standard global normalisation method in terms of noise reduction
      and signal retention. Conclusions. The SCS normalisation results using 16
      macroarray data sets from a Bacillus subtilis experiment confirm that the method
      is capable of reducing undesirable experimental variation whilst retaining
      important biological information. The ease and speed of implementation mean that
      this method can be easily adapted to other multicondition time/strain series
      single colour array data.

PMID- 17538692
TI  - Robert Boyle's memoirs for the natural history of human blood (1684): print,
      manuscript and the impact of baconianism in seventeenth-century medical science.

PMID- 17538693
TI  - Mechanistic pathology and therapy in the medical Assayer of Marcello Malpighi.

PMID- 17538694
TI  - Johann Heinrich Cohausen (1665-1750), salt iatrochemistry, and theories of
      longevity in his satire, Hermippus Redivivus (1742).

PMID- 17538695
TI  - Emil Behring's medical culture: from disinfection to serotherapy.

PMID- 17538696
TI  - Heredity and alcoholism in the medical sphere: the Netherlands, 1850-1900.

PMID- 17538697
TI  - A Persian anatomical image in a non-muslim manuscript from Gujarat.

PMID- 17538698
TI  - Approach to the asymptomatic patients with Brugada syndrome.
AB  - Brugada syndrome is an arrhythmogenic disease characterized by an ECG pattern of
      coved-type ST segment elevation in the right precordial leads and an increased
      risk of sudden cardiac death (SCD) as a result of polymorphic ventricular
      tachyarrhythmia or ventricular fibrillation (VF). Data from large patient studies
      and a meta-analysis of previous reports have shown that patients with a history
      of syncope or SCD and a spontaneous type 1 Brugada type ECG are at high risk for
      SCD. However, risk stratification of asymptomatic patients with Brugada type ECG
      is still a challenge. In particular, the use of electrophysiological study (EPS)
      for risk stratification remains controversial. Although some investigators have
      reported the possibility of use of EPS for distinguishing between high- and low
      risk patients with Brugada type ECG, no precise predictor of risk for SCD in
      asymptomatic patients has yet been determined. The approach to treatment of these
      patients is thus still unclear. Large clinical prospective studies with uniform
      diagnostic criteria and protocols for EPS as well as extended follow-up periods
      of over ten years are required for prediction of SCD.

PMID- 17538699
TI  - Ventricular arrhythmia discriminator programming and the impact on the incidence
      of inappropriate therapy in patients with implantable cardiac defibrillators.
AB  - BACKGROUND: The incidence of inappropriate therapy from implantable cardioverter
      defibrillators (ICDs) has been reduced by programming ventricular arrhythmia
      discriminators (VAD) on at the time of implant. OBJECTIVE: To determine which VAD
      is most effective in preventing inappropriate therapy. METHODS AND RESULTS: Dual
      chamber ICD (n=48) or cardiac resynchronization therapy defibrillator (CRT-D)
      (n=55) implantation was performed in 103 patients (M=94, F=9). Patients were
      followed prospectively for therapy events (shock or anti-tachycardia pacing) for
      a mean 362+/-289 days. Events were correlated with clinical characteristics and
      VAD programming. Of the 103 pts followed, 11 received inappropriate therapy (IT),
      15 received appropriate therapy (AT), and 77 received no therapy (NT). In the AT
      and IT groups, a total of 207 events (ATP=171, shock=36) were observed. A total
      of sixty-four electrograms (EGMs) were analyzed. Programming VADs "ON" versus
      "OFF" reduced the incidence of IT events compared to those receiving AT or NT
      events (p<.01), with a trend in fewer patients receiving IT (31.3% "ON" vs 55.6%
      "OFF", p = 0.131). Programming atrial fibrillation (AF) detection ON resulted in
      fewer patients receiving IT compared to those receiving AT or NT (3.6% vs 19%,
      p<.05). Furthermore, programming AF or AFL algorithms "ON", resulted in overall
      fewer episodes of IT therapy (p<.01). CONCLUSION: AF or AFL discriminators
      significantly reduced the incidence of IT, and were predominantly responsible for
      the benefits from VAD programming observed in this study. Activating these
      features as part of routine ICD or CRT-D programming may provide a simple and
      effective alternative to the use of more complex and multiple VAD strategies.

PMID- 17538700
TI  - Impact of hemodialysis on P-wave amplitude, duration, and dispersion.
AB  - Atrial fibrillation (AF) is a frequent arrhythmia in patients undergoing
      hemodialysis (HD). P wave duration (PWdu) and P wave dispersion (PWdi) have been
      shown to be predictors of emerging AF in different clinical conditions. We sought
      to study the impact of HD on PWdu, PWdi, and P wave amplitude in a cohort of
      patients undergoing HD. Seventeen patients (8 men, 31+/-10 years) were studied.
      Echocardiography parameters, the sum of the amplitude of P waves in all 12 ECG
      leads (SP), mean PWdu, and PWdi, along with a host of other parameters (body
      weight, heart rate, electrolytes and hemoglobin/hematochrit) were measured 1/2h,
      before and after, HD. SP increased (11.8+/-3.9 vs 15.3+/-4.0 mm, p = 0.004), mean
      PWdu remained stable (82.7+/-11.1 vs 81.6+/-10.5 ms, p = 0.606), PWdi decreased
      (51.7+/-19.1 vs 41.7+/-19.1 ms, p = 0.03), and left atrial dimension decreased
      (37.96+/-3.90 vs 30.62+/-3.38 mm, p = 0.0001), after HD. The change in PWdi
      correlated with fluid removed by HD (r = -0.55, p = 0.022). Re-measurements of P
      wave parameters in a random group of 11 of the 17 patients revealed augmented SP
      (p = 0.01), and stable mean PWdu (p = 0.36), and PWdi (p = 0.31), after HD. Fluid
      removed by HD leads to an increase in SP, a stable mean PWdu, and decrease (or
      stability on re-measurement in a subgroup of patients) in PWdi. Stability of PWdu
      may be due to the effects of augmentation of the P-wave amplitude and the
      reduction of the left atrial volume, cancelling each other. Variability of PWdi
      may stem from the occasional impossibility to measure PWdu (or measure it
      correctly) in minute P-waves in certain ECG leads, which in turn profoundly
      affects the PWdi.

PMID- 17538701
TI  - Pulmonary vein isolation with a multielectrode basket catheter.
AB  - Pulmonary vein (PV) isolation (PVI) techniques have evolved as a curative
      treatment of atrial fibrillation (AF) since PVI guided by circumferential mapping
      with a circular catheter was initially proposed. A multielectrode basket catheter
      (MBC) is also useful for PVI because of some advantages; (1) an MBC provides some
      information about the PV anatomy on the fluoroscopic image, (2) an MBC can
      utilize the non-fluoroscopic navigation system, (3) an MBC enables the direct
      three-dimensional mapping around the PV ostium and antrum, (4) the distal
      electrodes of the MBC can be used to monitor some activation changes within the
      PV in real time and thereby indicate the effects of ablation at the ostium and
      antrum as radiofrequency lesions are created. PVI with an MBC is an effective and
      safe procedure to cure AF by integrating the PV anatomy and electrophysiology in
      combination with a non-fluoroscopic three-dimensional navigation system for the
      ablation catheter.

PMID- 17538702
TI  - Permanent parahisian pacing.
AB  - Right Ventricular Apical permanent pacing could have negative hemodynamic
      effects. A physiologic pacing modality should preserve a correct atrio
      ventricular and interventricular synchronization. This can be obtained through
      biventricular pacing, left ventricular pacing, or from alternative right
      ventricular pacing sites. Direct His Bundle Pacing (DHBP) was documented as
      reliable and effective for preventing the desynchronization and negative effects
      of right ventricular apical pacing. It is, however, a complex method that
      requires longer average implant times, cannot be carried out on all patients and
      presents high pacing thresholds. On the contrary, the parahisian pacing, with
      simpler feasibility and reliability criteria, seems to guarantee an early
      invasion of the His-Purkinje conduction system, with a physiological ventricular
      activation, very similar to the one that can be obtained with direct His bundle
      pacing. We present our experience on 68 patients who underwent a permanent right
      ventricular pacing in hisian/parahisian region, for advanced AV block and narrow
      QRS. In the first 17 patients we performed a double-blind randomized controlled
      study, with two 6-months cross-over periods in parahisian and apical pacing,
      documenting a significant improvement of NYHA class, exercise tolerance, quality
      of life score, mitral and tricuspidal regurgitation degree, and interventricular
      mechanical delay. In the subsequent 51 patients, in a mean follow of 21
      months/patient, the pacing threshold remained stable (0.7+/-0.5 V implant; 0.9+/
      0.7 V follow-up; p=0.08). The ejection fraction maintained medium-long term
      stable values, confirming the fact that the parahisian pacing can prevent
      deterioration of the left ventricular function. Parahisian pacing, therefore, has
      proven to be a reliable method, easy to apply and effective in preventing the
      negative effects induced by non-physiological right ventricular apical pacing.

PMID- 17538703
TI  - Pulmonary vein isolation by high intensity focused ultrasound.
AB  - Pulmonary vein isolation (PVI) using radiofrequency current (RFC) ablation is a
      potentially curative treatment option for patients with atrial fibrillation (AF).
      The shortcomings of the RFC technology (technically challenging, long procedure
      times, complications) steadily kindle the interest in new energy sources and
      catheter designs. High intensity focused ultrasound (HIFU) has the ability to
      precisely focus ultrasound waves in a defined area with a high energy density.
      HIFU balloon catheters (BC) positioned at the PV ostia appear to be an ideal tool
      to transmit the ablation energy in a circumferential manner to the PV ostia and
      may therefore bear substantial advantage over conventional ablation catheters in
      PVI procedures. In clinical trials the HIFU BC has shown promising success rates
      similar to RFC catheter ablation for PVI in patients with AF. However, procedure
      times are still long and serious complications have been observed. Therefore, it
      may be a valuable alternative to the conventional techniques in selected patients
      but further clinical trials have to be initiated.

PMID- 17538704
TI  - Catheter ablation of atrial incisional tachycardia mistaken for atrial flutter.
AB  - Incisional sustained tachycardias are frequent in patients who have undergone a
      surgical repair of interatrial defect. A 43-year-old woman with drug refractory,
      highly symptomatic, persistent atrial tachycardia in the last year, was referred
      to our unit for catheter ablation. The patient had undergone a cardiac operation
      for repairing interatrial secundum ostium type defect with a patch five years
      before. A previous radiofrequency ablation procedure had been performed for
      common atrial flutter. We describe a case of incisional atrial tachycardia
      ablation guided by the new EnSite NavX system equipped with a new electroanatomic
      mapping system.

PMID- 17538708
TI  - Comparative study and improvement of current cell micro-patterning techniques.
AB  - The original micropatterning technique on gold, although very efficient, is not
      accessible to most biology labs and is not compatible with their techniques for
      image acquisition. Other solutions have been developed on silanized glass
      coverslips. These methods are still hardly accessible to biology labs and do not
      provide sufficient reproducibility to become incorporated in routine biological
      protocols. Here, we analyzed cell behavior on micro-patterns produced by various
      alternative techniques. Distinct cell types displayed different behavior on
      micropatterns, while some were easily constrained by the patterns others escaped
      or ripped off the patterned adhesion molecules. We report methods to overcome
      some of these limitations on glass coverslips and on plastic dishes which are
      compatible with our experimental biological applications. Finally, we present a
      new method based on UV crosslinking of adhesion proteins with benzophenone to
      easily and rapidly produce highly reproducible micropatterns without the use of a
      microfabricated elastomeric stamp.

PMID- 17538709
TI  - A practical guide to microfluidic perfusion culture of adherent mammalian cells.
AB  - Culturing cells at microscales allows control over microenvironmental cues, such
      as cell-cell and cell-matrix interactions; the potential to scale experiments;
      the use of small culture volumes; and the ability to integrate with microsystem
      technologies for on-chip experimentation. Microfluidic perfusion culture in
      particular allows controlled delivery and removal of soluble biochemical
      molecules in the extracellular microenvironment, and controlled application of
      mechanical forces exerted via fluid flow. There are many challenges to designing
      and operating a robust microfluidic perfusion culture system for routine culture
      of adherent mammalian cells. The current literature on microfluidic perfusion
      culture treats microfluidic design, device fabrication, cell culture, and micro
      assays independently. Here we systematically present and discuss important design
      considerations in the context of the entire microfluidic perfusion culture
      system. These design considerations include the choice of materials, culture
      configurations, microfluidic network fabrication and micro-assays. We also
      present technical issues such as sterilization; seeding cells in both 2D and 3D
      configurations; and operating the system under optimized mass transport and shear
      stress conditions, free of air-bubbles. The integrative and systematic treatment
      of the microfluidic system design and fabrication, cell culture, and micro-assays
      provides novices with an effective starting point to build and operate a robust
      microfludic perfusion culture system for various applications.

PMID- 17538710
TI  - Survival, migration and differentiation of retinal progenitor cells transplanted
      on micro-machined poly(methyl methacrylate) scaffolds to the subretinal space.
AB  - Stem and progenitor cells can be combined with polymer substrates to generate
      tissue equivalents in culture. The replacement of retinal tissue lost to disease
      or trauma using retinal progenitor cells (RPCs) delivered on polymer scaffolds
      and transplanted into the sub-retinal space of the damaged retina is a promising
      therapeutic strategy. Micromachining-based, ultra-thin PMMA poly(methyl
      methacrylate) scaffolds may provide a suitable cytoarchitectural environment for
      tissue engineering and transplantation to the diseased eye. Here, adhesion of
      RPCs to polymer, as well as migration and differentiation in the host retina were
      compared for PMMA scaffolds (6 microm thickness) with either smooth or porous (11
      microm diameter) surface topography. RPCs were cultured under identical
      conditions on smooth or porous laminin-coated polymer scaffolds and transplanted
      into the subretinal space of C57BL/6 mice. RPCs could be cultured on both
      scaffolds with similar results, although transplantation with non-porous
      scaffolds showed limited RPC retention. Porous scaffolds demonstrated enhanced
      RPC adherence during transplantation and allowed for greater process outgrowth
      and cell migration into the host retinal layers. Integrated cells expressed the
      mature neuronal marker neurofilament-200 (nf-200), the glial marker glial
      fibrillary acidic protein (GFAP) and the retinal-specific marker recoverin. No
      host foreign body response was seen. In conclusion, ultra-thin film PMMA
      scaffolds micromachined to contain through pores retain adherent RPCs to a
      considerably greater extent than unmachined versions during the transplantation
      process and can serve as a biocompatible substrate for cell delivery in vivo.

PMID- 17538711
TI  - Multiphase electropatterning of cells and biomaterials.
AB  - Tissues formed by cells encapsulated in hydrogels have uses in biotechnology,
      cell-based assays, and tissue engineering. We have previously presented a 3D
      micropatterning technique that rapidly localizes live cells within hydrogels
      using dielectrophoretic (DEP) forces, and have demonstrated the ability to
      modulate tissue function through the control of microscale cell architecture. A
      limitation of this method is the requirement that a single biomaterial must
      simultaneously harbor biological properties that support cell survival and
      function and material properties that permit efficient dielectrophoretic
      patterning. Here, we resolve this issue by forming multiphase tissues consisting
      of microscale tissue sub-units in a 'local phase' biomaterial, which, in turn,
      are organized by DEP forces in a separate, mechanically supportive 'bulk phase'
      material. We first define the effects of medium conductivity on the speed and
      quality of DEP cell patterning. As a case study, we then produce multiphase
      tissues with microscale architecture that combine high local hydrogel
      conductivity for enhanced survival of sensitive liver progenitor cells with low
      bulk conductivity required for efficient DEP micropatterning. This approach
      enables an expanded range of studies examining the influence of 3D cellular
      architecture on diverse cell types, and in the future may improve the biological
      function of inhomogeneous tissues assembled from a variety of modular tissue sub
      units.

PMID- 17538712
TI  - Micro-bioreactor array for controlling cellular microenvironments.
AB  - High throughput experiments can be used to spatially and temporally investigate
      the many factors that regulate cell differentiation. We have developed a micro
      bioreactor array (MBA) that is fabricated using soft lithography and contains
      twelve independent micro-bioreactors perfused with culture medium. The MBA
      enables cultivation of cells that are either attached to substrates or
      encapsulated in hydrogels, at variable levels of hydrodynamic shear, and with
      automated image analysis of the expression of cell differentiation markers. The
      flow and mass transport in the MBA were characterized by computational fluid
      dynamic (CFD) modeling. The representative MBA configurations were validated
      using the C2C12 cell line, primary rat cardiac myocytes and human embryonic stem
      cells (hESCs) (lines H09 and H13). To illustrate the utility of the MBA for
      controlled studies of hESCs, we established correlations between the expression
      of smooth muscle actin and cell density for three different flow configurations.

PMID- 17538713
TI  - Fabrication of microfluidic hydrogels using molded gelatin as a sacrificial
      element.
AB  - This paper describes a general procedure for the formation of hydrogels that
      contain microfluidic networks. In this procedure, micromolded meshes of gelatin
      served as sacrificial materials. Encapsulation of gelatin meshes in a hydrogel
      and subsequent melting and flushing of the gelatin left behind interconnected
      channels in the hydrogel. The channels were as narrow as approximately 6 microm,
      and faithfully replicated the features in the original gelatin mesh. Fifty
      micrometre wide microfluidic networks in collagen and fibrin readily enabled
      delivery of macromolecules and particles into the channels and transport of
      macromolecules from channels into the bulk of the gels. Microfluidic gels were
      also suitable as scaffolds for cell culture, and could be seeded by human
      microvascular endothelial cells to form rudimentary endothelial networks for
      potential use in tissue engineering.

PMID- 17538714
TI  - Understanding microchannel culture: parameters involved in soluble factor
      signaling.
AB  - While the importance of autocrine-paracrine signaling in vivo is clear, the
      ability to study the effects of secreted endogenous factors in vitro is hampered
      by canonical culture platforms. In multi-well plates, the large air-liquid
      interface gives rise to convective flows that continually mix the fluid
      disrupting the local diffusion-based accumulation. Simple microchannels provide a
      more controlled microenvironment that can be used to study secreted factor
      effects. Here, we utilize microchannel culture to examine basic culture
      parameters and their interactions using normal mammary gland epithelial cells
      (NMuMG). The following parameters were studied: (1) cell density (80 vs. 240
      cells mm(-2)), (2) exogenous growth factors (epidermal growth factor [EGF] vs.
      fetal bovine serum), (3) medium change frequency (1 h, 4 h, 12 h), and (4)
      culture platform (microchannels vs. 96-well plates). The cells exhibited
      increased growth rates in microchannels as compared to 96-well plates. Cell
      proliferation increased as the frequency of media change decreased. For the
      microchannel geometries used, important threshold concentrations were reached in
      a few hours. In aggregate, the results indicate that the function of the four
      factors and their interactions on NMuMG growth are spatially and temporally
      related by molecular diffusion in the controlled microchannel space. The
      convective-free microchannel environment may prove useful for studying soluble
      factor signaling in vitro, and to test models and predictions of autocrine
      paracrine signaling.

PMID- 17538715
TI  - Microfluidic systems to examine intercellular coupling of pairs of cardiac
      myocytes.
AB  - In this paper we describe a microfluidic environment that enables us to explore
      cell-to-cell signalling between longitudinally linked primary heart cells. We
      have chosen to use pairs (or doublets) of cardiac myocyte as a model system, not
      only because of the importance of cell-cell signalling in the study of heart
      disease but also because the single cardiomyocytes are both mechanically and
      electrically active and their synchronous activation due to the intercellular
      coupling within the doublet can be readily monitored on optical and electrical
      recordings. Such doublets have specialised intercellular contact structures in
      the form of the intercalated discs, comprising the adhesive junction (fascia
      adherens and macula adherens or desmosome) and the connecting junction (known as
      gap junction). The latter structure enables adjacent heart cells to share ions,
      second messengers and small metabolites (<1 kDa) between them and thus provides
      the structural basis for the synchronous (syncytical) behaviour of connected
      cardiomyocytes. Using the unique environment provided by the microfluidic system,
      described in this paper, we explore the local ionic conditions that enable the
      propagation of Ca(2+) waves between two heart cells. We observe that the ability
      of intracellular Ca(2+) waves to traverse the intercalated discs is dependent on
      the relative concentrations of diastolic Ca(2+) in the two adjacent cells. These
      experiments rely upon our ability to independently control both the electrical
      stimulation of each of the cells (using integrated microelectrodes) and to
      rapidly change (or switch) the local concentrations of ions and drugs in the
      extracellular buffer within the microfluidic channel (using a nanopipetting
      system). Using this platform, it is also possible to make simultaneous optical
      recordings (including fluorescence and cell contraction) to explore the effect of
      drugs on one or both cells, within the doublet.

PMID- 17538716
TI  - High-density microfluidic arrays for cell cytotoxicity analysis.
AB  - In this paper, we report on the development of a multilayer elastomeric
      microfluidic array platform for the high-throughput cell cytotoxicity screening
      of mammalian cell lines. Microfluidic channels in the platform for cell seeding
      are orthogonal to channels for toxin exposure, and within each channel
      intersection is a circular chamber with cell-trapping sieves. Integrated,
      pneumatically-actuated elastomeric valves within the device isolate the
      microchannel array within the device into parallel rows and columns for cell
      seeding and toxin exposure. As a demonstration of the multiplexing capability of
      the platform, a microfluidic array containing 576 chambers was used to screen
      three cell types (BALB/3T3, HeLa, and bovine endothelial cells) against a panel
      of five toxins (digitonin, saponin, CoCl(2), NiCl(2), acrolein). Evaluation of on
      chip cell morphology and viability was carried out using fluorescence microscopy,
      with outcomes comparable to microtiter plate cytotoxicity assays. Using this
      scalable platform, cell seeding and toxin exposure can be carried out within a
      single microfluidic device in a multiplexed format, enabling high-density
      parallel cytotoxicity screening while minimizing reagent consumption.

PMID- 17538717
TI  - Cell detection and counting through cell lysate impedance spectroscopy in
      microfluidic devices.
AB  - Cell-based microfluidic devices have attracted interest for a wide range of
      applications. While optical cell counting and flow cytometry-type devices have
      been reported extensively, sensitive and efficient non-optical methods to detect
      and quantify cells attached over large surface areas within microdevices are
      generally lacking. We describe an electrical method for counting cells based on
      the measurement of changes in conductivity of the surrounding medium due to ions
      released from surface-immobilized cells within a microfluidic channel.
      Immobilized cells are lysed using a low conductivity, hypotonic media and the
      resulting change in impedance is measured using surface patterned electrodes to
      detect and quantify the number of cells. We found that the bulk solution
      conductance increases linearly with the number of isolated cells contributing to
      solution ion concentration. The method of cell lysate impedance spectroscopy is
      sensitive enough to detect 20 cells microL(-1), and offers a simple and efficient
      method for detecting and enumerating cells within microfluidic devices for many
      applications including measurement of CD4 cell counts in HIV patients in resource
      limited settings. To our knowledge, this is the most sensitive approach using non
      optical setups to enumerate immobilized cells. The microfluidic device, capable
      of isolating specific cell types from a complex bio-fluidic and quantifying cell
      number, can serve as a single use cartridge for a hand-held instrument to provide
      simple, fast and affordable cell counting in point-of-care settings.

PMID- 17538718
TI  - A cell-laden microfluidic hydrogel.
AB  - The encapsulation of mammalian cells within the bulk material of microfluidic
      channels may be beneficial for applications ranging from tissue engineering to
      cell-based diagnostic assays. In this work, we present a technique for
      fabricating microfluidic channels from cell-laden agarose hydrogels. Using
      standard soft lithographic techniques, molten agarose was molded against a SU-8
      patterned silicon wafer. To generate sealed and water-tight microfluidic
      channels, the surface of the molded agarose was heated at 71 degrees C for 3 s
      and sealed to another surface-heated slab of agarose. Channels of different
      dimensions were generated and it was shown that agarose, though highly porous, is
      a suitable material for performing microfluidics. Cells embedded within the
      microfluidic molds were well distributed and media pumped through the channels
      allowed the exchange of nutrients and waste products. While most cells were found
      to be viable upon initial device fabrication, only those cells near the
      microfluidic channels remained viable after 3 days, demonstrating the importance
      of a perfused network of microchannels for delivering nutrients and oxygen to
      maintain cell viability in large hydrogels. Further development of this technique
      may lead to the generation of biomimetic synthetic vasculature for tissue
      engineering, diagnostics, and drug screening applications.

PMID- 17538719
TI  - A hydrogel-based microfluidic device for the studies of directed cell migration.
AB  - We have developed a hydrogel-based microfluidic device that is capable of
      generating a steady and long term linear chemical concentration gradient with no
      through flow in a microfluidic channel. Using this device, we successfully
      monitored the chemotactic responses of wildtype Escherichia coli (suspension
      cells) to alpha-methyl-DL-aspartate (attractant) and differentiated HL-60 cells
      (a human neutrophil-like cell line that is adherent) to formyl-Met-Leu-Phe (f
      MLP, attractant). This device advances the current state of the art in
      microchemotaxis devices in that (1) it demonstrates the validity of using
      hydrogels as the building material for a microchemotaxis device; (2) it
      demonstrates the potential of the hydrogel based microfluidic device in
      biological experiments since most of the proteins and nutrients essential for
      cell survival are readily diffusible in hydrogel; (3) it is capable of applying
      chemical stimuli independently of mechanical stimuli; (4) it is straightforward
      to make, and requires very basic tools that are commonly available in biological
      labs. This device will also be useful in controlling the chemical and mechanical
      environment during the formation of tissue engineered constructs.

PMID- 17538720
TI  - Efficient formation of uniform-sized embryoid bodies using a compartmentalized
      microchannel device.
AB  - The formation of spherical aggregates of cells called embryoid bodies (EBs) is an
      indispensable step in many protocols in which embryonic stem (ES) cells are
      differentiated to other cell types. Appropriate morphology and embryo size are
      critical for the sequential developmental stages of naturally conceived embryos.
      Likewise, regulating the size of EBs and the timing of their formation is crucial
      for controlling the differentiation of ES cells within the EB. Existing methods
      of formation of EBs, however, are tedious or provide heterogeneously-sized EBs.
      Here we describe a microfluidic system for straightforward synchronized formation
      of uniform-sized EBs, the size of which can be controlled by changing the cross
      sectional size of microchannels in the microfluidic device. The device consists
      of two microchannels separated by a semi-porous polycarbonate membrane treated to
      be resistant to cell adhesion. ES cells introduced into the upper channel self
      aggregate to form uniformly-sized EBs. The semi-porous membrane also allows
      subsequent treatment of the non-attached EBs with different reagents from the
      lower channel without the need for wash out because of the compartmentalization
      afforded by the membrane. This method provides a simple yet robust means to
      control the formation of EBs and the subsequent differentiation of ES cells in a
      format compatible for ES cell processing on a chip.

PMID- 17538721
TI  - A chip-based platform for the in vitro generation of tissues in three-dimensional
      organization.
AB  - We describe a multi-purpose platform for the three-dimensional cultivation of
      tissues. The device is composed of polymer chips featuring a microstructured area
      of 1-2 cm(2). The chip is constructed either as a grid of micro-containers
      measuring 120-300 x 300 x 300 microm (h x l x w), or as an array of round
      recesses (300 microm diameter, 300 microm deep). The micro-containers may be
      separately equipped with addressable 3D-micro-electrodes, which allow for
      electrical stimulation of excitable cells and on-site measurements of
      electrochemically accessible parameters. The system is applicable for the
      cultivation of high cell densities of up to 8 x 10(6) cells and, because of the
      rectangular grid layout, allows the automated microscopical analysis of
      cultivated cells. More than 1000 micro-containers enable the parallel analysis of
      different parameters under superfusion/perfusion conditions. Using different
      polymer chips in combination with various types of bioreactors we demonstrated
      the principal suitability of the chip-based bioreactor for tissue culture
      applications. Primary and established cell lines have been successfully
      cultivated and analysed for functional properties. When cells were cultured in
      non-perfused chips, over time a considerable degree of apoptosis could be
      observed indicating the need for an active perfusion. The system presented here
      has also been applied for the differentiation analysis of pluripotent embryonic
      stem cells and may be suitable for the analysis of the stem cell niche.

PMID- 17538722
TI  - Controlling size, shape and homogeneity of embryoid bodies using poly(ethylene
      glycol) microwells.
AB  - Directed differentiation of embryonic stem (ES) cells is useful for creating
      models of human disease and could potentially generate a wide array of functional
      cell types for therapeutic applications. Methods to differentiate ES cells often
      involve the formation of cell aggregates called embryoid bodies (EBs), which
      recapitulate early stages of embryonic development. EBs are typically made from
      suspension cultures, resulting in heterogeneous structures with a wide range of
      sizes and shapes, which may influence differentiation. Here, we use
      microfabricated cell-repellant poly(ethylene glycol) (PEG) wells as templates to
      initiate the formation of homogenous EBs. ES cell aggregates were formed with
      controlled sizes and shapes defined by the geometry of the microwells. EBs
      generated in this manner remained viable and maintained their size and shape
      within the microwells relative to their suspension counterparts. Intact EBs could
      be easily retrieved from the microwells with high viability (>95%). These results
      suggest that the microwell technique could be a useful approach for in vitro
      studies involving ES cells and, more specifically, for initiating the
      differentiation of EBs of greater uniformity based on controlled
      microenvironments.

PMID- 17538723
TI  - The melting point of hexagonal ice (Ih) is strongly dependent on the quadrupole
      of the water models.
AB  - It is shown that quadrupolar interactions play a determinant role in the melting
      temperatures of common water models and that there is a simple relationship
      between the strength of the quadrupolar forces and the position of the negative
      charge; our conclusion is that acceptable predictions for the melting temperature
      can only be obtained when the negatively charged site is shifted from the oxygen
      atom towards the hydrogens.

PMID- 17538724
TI  - Dumbbells and onions in ternary nucleation.
AB  - Molecular simulations for a ternary nucleation system (water/n-nonane/1-butanol)
      demonstrate a more complex nucleation mechanism than previously thought, where
      critical nuclei with different compositions are present even for a given vapour
      phase composition; the spatial distribution in these critical nuclei is
      heterogeneous and dumbbell and onion motifs are found; in the former, water and
      nonane nano-droplets are connected through a butanol handle, while in the latter
      a water core is surrounded by a nonane corona with an interfacial butanol shell.

PMID- 17538725
TI  - On the nature of hydrogen bonds: an overview on computational studies and a word
      about patterns.
AB  - The nature of hydrogen bond interactions (HB) is still today the subject of many
      discussions. We present an overview of computational methods and parameters
      (interaction energy, HB distance and radii, electron density topological
      parameters or orbital energies) required for an accurate description of HB
      systems. As well, we present the different correlations that have been found
      between these descriptors providing a global view of HB interactions. A synopsis
      of the different HBs reported in terms of their strength was presented.
      Considering the definitions of covalent and ionic bonds, HB interactions could
      occur between these two extremes. Thus, we look into some of the very strong HBs
      (LBHB, CAHB, RAHB) and some of the weak HBs (weak donors: C-H or weak acceptors:
      pi systems). Subsequently, aspects such as cooperativity or solvation are
      examined. Finally, we present a study on multiple "parallel" and "bifurcated" HB
      systems. Our results indicate that HB pattern and electron density determine the
      strength of the interaction and that "parallel" HB interactions are more stable
      than the "bifurcated" ones.

PMID- 17538726
TI  - Calculation and analysis of NMR spin-spin coupling constants.
AB  - The analysis of NMR spin-spin coupling leads to a unique insight into the
      electronic structure of closed-shell molecules, provided one is able to decode
      the different features of the spin-spin coupling mechanism. For this purpose, the
      physics of spin-spin coupling is described and the way how spin-spin coupling
      constants (SSCCs) can be quantum mechanically determined. Based on this insight,
      a set of requirements is derived that guide the development of a quantum
      mechanical analysis of spin-spin coupling. It is demonstrated that the J-OC-PSP
      (=J-OC-OC-PSP: Decomposition of J into orbital contributions using orbital
      currents and partial spin polarization) analysis method fulfills all
      requirements. J-OC-PSP makes it possible to partition the isotropic indirect SSCC
      J or its reduced analogue K as well as the four Ramsey terms (Fermi contact (FC),
      spin dipole (SD), diamagnetic spin orbit (DSO), paramagnetic spin orbit (PSO))
      leading to J (or K) into Cartesian components (for the anisotropic Ramsey terms
      SD, DSO, PSO), orbital contributions or electron interaction terms. For the
      purpose of decoding the spin-spin coupling mechanism, FC, SD, DSO, and PSO
      coupling is discussed in detail and related to electronic and bonding features of
      the molecules in question. The myth of empirical and semiempirical relationships
      between SSCCs and bonding features is unveiled. It is found that most
      relationships are only of limited, partly dubious value, often arising from a
      fortuitous cancellation of terms that cannot be expected in general. These
      relationships are replaced by quantum chemical relations and descriptions that
      directly reflect the complex electronic processes leading to spin-spin coupling.

PMID- 17538727
TI  - What have we learnt about heavy carbenes through laser flash photolysis studies?
AB  - Time resolved gas-phase kinetic studies have contributed a great deal of
      fundamental information about the reactions and reactivity of heavy carbenes
      (silylenes, germylenes and stannylenes) during the past two decades. In this
      article we trace the development of our understanding through the mechanistic
      themes of intermediate complexes, third body assisted associations, catalysed
      reactions, non-observed reactions and substituent effects. Ab initio (quantum
      chemical) calculations have substantially assisted mechanistic interpretation and
      are discussed where appropriate. Trends in reactivity are identified and some
      signposts to future studies are indicated. This review, although detailed, is not
      comprehensive.

PMID- 17538728
TI  - Transport properties of asymmetric-top molecules.
AB  - Kinetic theory of gases is extended from linear molecules to asymmetric tops. The
      integration over the velocity of the centre of mass is carried out explicitly and
      the results are expressed in a form suitable for classical evaluation. These
      results can also be employed for spherical and symmetric tops.

PMID- 17538729
TI  - Computing steady-state metal flux at microorganism and bioanalogical sensor
      interfaces in multiligand systems. A reaction layer approximation and its
      comparison with the rigorous solution.
AB  - In complicated environmental or biological systems, the fluxes of chemical
      species at a consuming interface, like an organism or an analytical sensor,
      involve many coupled chemical and diffusion processes. Computation of such fluxes
      thus becomes difficult. The present paper describes an approximate approach,
      based on the so-called reaction layer concept, which enables one to obtain a
      simple analytical solution for the steady-state flux of a metal ion at a
      consuming interface, in the presence of many ligands, which are in excess with
      respect to the test metal ion. This model can be used for an unlimited number of
      ligands and complexes, without limit for the values of the
      association/dissociation rate constants or diffusion coefficients. This
      approximate solution is compared with a rigorous approach for the computation of
      the fluxes based on an extension of a previously published method (J. Galceran,
      J. Puy, J. Salvador, J. Cecilia, F. Mas and J. L. Garces, Phys. Chem. Chem.
      Phys., 2003, 5, 5091-5100). The comparison is performed for a very wide range of
      the key parameters: rate constants and diffusion coefficients, equilibrium
      constants and ligand concentrations. Their combined influence is studied in the
      whole domain of fully labile to non-labile complexes, via two combination
      parameters: the lability index, L, and the reaction layer thickness, mu. The
      results show that the approximate solution provides accurate results in most
      cases. However, for particular combinations of metal complexes with specific
      values of L or mu, significant differences between the approximate and rigorous
      solutions may occur. They are evaluated and discussed. These results are
      important for three reasons: (i) they enable the use of the approximate solution
      in a fully reliable manner, (ii) when present, the differences between
      approximate and rigorous solution are largely due to the coupling of chemical
      reactions, whose importance can thus be estimated, (iii) due to its simple
      mathematical expression, the individual contribution of each metal species to the
      overall flux can be computed.

PMID- 17538730
TI  - Dissociative recombination of the deuterated acetaldehyde ion, CD3CDO(+): product
      branching fractions, absolute cross sections and thermal rate coefficient.
AB  - Dissociative recombination of the deuterated acetaldehyde ion CD3CDO(+) has been
      studied at the heavy-ion storage ring CRYRING, located at the Manne Siegbahn
      Laboratory, Stockholm, Sweden. Product branching fractions together with absolute
      DR cross-sections were measured. The branching fractions were determined at a
      relative collision energy between the ions and the electrons of approximately 0
      eV. With a probability of 34% the DR events resulted in no ruptures of bonds
      between heavy atoms (i.e. no breakage of the C-C bond or the C[double bond,
      length as m-dash]O bond). In the remaining 66% of the events one of the bonds
      between the heavy atoms was broken. The energy-dependent cross-section for the DR
      reaction was measured between approximately 0 and 1 eV relative kinetic energy.
      In the energy region between 1 meV and 0.2 eV the absolute cross section could be
      fitted by the expression sigma(E) = 6.8 x 10(-16)E(-1.28) cm(2), whereas in the
      energy interval between 0.2 and 1 eV the data were best fitted by sigma(E) = 4.1
      x 10(-16)E(-1.60) cm(2). From these cross section data the thermal rate
      coefficient (as a function of the electron temperature), alpha(T) = 9.2 x 10(-7)
      (T/300)(-0.72) cm(3) s(-1) was obtained.

PMID- 17538731
TI  - Coupled-cluster studies of the lowest excited states of the 11-cis-retinal
      chromophore.
AB  - The first few excited states of the 11-cis-retinal (PSB11) chromophore have been
      studied at the coupled-cluster approximative singles and doubles (CC2) level
      using triple-zeta quality basis sets augmented with double sets of polarisation
      functions. The two lowest vertical excitation energies of 2.14 and 3.21 eV are in
      good agreement with recently reported experimental values of 2.03 and 3.18 eV
      obtained in molecular beam measurements. Calculations at the time-dependent
      density functional theory (TDDFT) level using the B3LYP hybrid functional yield
      vertical excitation energies of 2.34 and 3.10 eV for the two lowest states. Zero
      point vibrational energy (ZPVE) corrections of -0.09 and -0.17 eV were deduced
      from the harmonic vibrational frequencies for the ground and excited states
      calculated at the density functional theory (DFT) and TDDFT level, respectively,
      using the B3LYP hybrid functional.

PMID- 17538732
TI  - Fourier transform infrared spectroscopy and ab initio theory of acid-hydrogen
      sulfide clusters: H2S-HCl, D2S-DCl and H2S-(HCl)(2).
AB  - The rotationally resolved Fourier transform infrared (FTIR) spectrum of the nu(s)
      HCl and DCl stretching bands for the hydrogen bonded complex H2S-HCl and its
      isotopomer D2S-DCl have been observed in a supersonic jet at 0.02 cm(-1)
      resolution. In the same experimental conditions, two additional bands observed
      without rotational structure in the HCl range of the dimer have been assigned to
      the cyclic trimer H2S-(HCl)(2). The multidimensional coupling picture involving
      the donor stretch mode nu(s) and low frequency intermolecular modes already
      evidenced in several medium strength hydrogen bonded complexes is beautifully
      confirmed by the observation of completely separated hot band progressions in the
      198 K cell spectrum of both dimers. Based on our anharmonic adiabatic approach
      for the treatment of the coupled vibrations, absolute vibrational frequencies,
      diagonal and off-diagonal anharmonicities as well as rovibrational coupling
      constants obtained from analyses of several 2-D subspaces at MP2 and CCSD(T)
      level are in excellent agreement with spectroscopic results. In the case of small
      light complexes, the combination of elevated rotational constants and a
      negligible contribution of intramolecular vibrational redistribution (IVR)
      improve the reliability of predissociation lifetime measurements, estimated to
      180 ps for H2S-HCl and above 200 ps for D2S-DCl.

PMID- 17538733
TI  - Similarities and differences on the molecular mechanism of CO oxidation on
      Rh(111) and bimetallic RhCu(111) surfaces.
AB  - The reaction between adsorbed CO and atomic O on various sites of Rh(111) and on
      the bimetallic RhCu(111) surface has been investigated by first principles
      density functional theory using slab models. The most likely reaction pathway for
      CO oxidation on Rh(111) involves probably migration of atomic oxygen from fcc to
      hcp sites. On the bimetallic surface the mechanism is similar, although depending
      on the type of bimetallic site a reduction of the energy barrier is predicted.
      Consequences for the NO reduction by CO reaction are analyzed.

PMID- 17538734
TI  - Low energy 13C+ and 13C2+ ion irradiation of water ice.
AB  - In this paper we report the results of the first experimental study of the
      irradiation of low temperature water ice (30 and 90 K) using low energy (4 keV)
      13C+ and 13C2+ ions. 13CO(2) and H2O(2) were readily formed within the H2O ice
      with the product yield and growth rate observed to be highly dependent on both
      the sample temperature and ion charge state.

PMID- 17538735
TI  - Hydrogen chemisorption on supported platinum, gold, and platinum-gold-alloy
      catalysts.
AB  - Alloyed catalysts receive considerable attention, because of their unique
      catalytic properties; they often show higher selectivity, activity, and stability
      compared to the pure metal particles. To provide insights in the origins of these
      features, we report the structure and the interaction of hydrogen with each of
      the metals in an intimately mixed platinum-gold catalyst and compare these
      characteristics to those in the single metal particles. X-Ray absorption
      spectroscopy (XAS) and electron microscopy analysis showed that the structure of
      the mixed particle differed from the single metal particles. The interaction of
      platinum with hydrogen is stronger than the H-Au interaction and the adsorption
      sites were different. EXAFS analysis showed that the structure of the platinum
      clusters changes with increasing hydrogen coverage, observed as a relaxation of
      the contracted Pt-Pt distance and an increase in the Pt-Pt coordination number.
      No such changes were observed for gold clusters. Well-mixed PtAu-alloy clusters,
      with a bulk Au-to-Pt ratio of two, supported on SiO(2), adsorb hydrogen on both
      platinum and gold atoms, which indicates that gold cannot be regarded as an inert
      metal. The heat of adsorption on the platinum ensembles does not decrease upon
      alloying; the weakening of the overall hydrogen adsorption strength when alloying
      platinum with gold is an ensemble-size effect.

PMID- 17538736
TI  - Endometriosis of the inguinal canal mimicking a hernia.
AB  - We report a 37-year-old Chinese woman who presented with a groin lump associated
      with constant and non-catamenial pain. Ultrasonography was suggestive of an
      inguinal hernia. Intraoperatively, an endometriotic lump with no laparoscopical
      evidence of endometriosis in the abdominopelvic region was found. Isolated
      endometriotic lesions in the inguinal canal is a rare occurrence. Surgeons,
      however, should consider this diagnosis in women of reproductive age who present
      with a painful groin lump.

PMID- 17538737
TI  - Postoperative complications due to a retained surgical sponge.
AB  - Retained surgical sponge or glossypiboma is a relatively common occurrence;
      however, surgeons may not report these events for fear of litigation and adverse
      publicity. We report postoperative complications in three cases due to retained
      surgical sponges. The first case, a 26-year-old woman, presented with gastric
      outlet obstruction due to the sponge obstructing the pyloric canal three weeks
      following cholecystectomy, which was completely relieved following endoscopical
      removal of the sponge. The second case, a 32-year-old woman, presented with
      repeated attacks of intestinal obstruction following cholecystectomy and tubal
      ligation and was treated with surgical removal of the sponge. The third patient,
      a 40-year-old woman, presented with features of colonic obstruction following
      hysterectomy. Colonoscopy revealed a partial migration of the sponge through the
      colonic wall and on laparotomy, she was found to have multiple internal fistulae
      between the small and large intestines, all occurring around the inflammation
      caused by the retained sponge.

PMID- 17538738
TI  - Lichen amyloidosis in an unusual location.
AB  - We report lichen amyloidosis occurring on the upper lip and nasolabial folds of a
      61-year-old woman from Singapore. She had a past history of systemic lupus
      erythematosus, which was in remission for three years. There had been no lesions
      of lupus erythematosus in this area. Clinically, the lesions were skin-coloured,
      firm papules and our differential diagnoses included trichoepithelioma, papular
      sarcoid or lupus miliaris disseminatus faciei. Skin biopsy from one of the
      lesions showed amyloid deposits in the dermis which were Congo red stain
      positive. These deposits also showed apple green birefringence.
      Immunohistochemical staining of the amyloid deposits stained positive for
      cytokeratins (CK) 5 and 6, and negative for CK 14. The kappa and lambda stains
      were equivocal. Further investigations, including multiple myeloma screen and
      rectal biopsy, ruled out systemic amyloidosis. There was no other evidence of
      cutaneous amyloidosis on her limbs or trunk. She refused treatment for her
      lesions. This case highlights the commonly-seen form of primary localised
      cutaneous amyloidosis in an unusual location.

PMID- 17538739
TI  - Extrapulmonary sarcoidosis: unusual cause of epiphora.
AB  - Sarcoidosis is a multisystemic granulomatous disease of unknown aetiology mainly
      affecting African-Americans, Scandinavians, and the Irish. However, individuals
      of other races and ethnicities are still not immune. The clinical presentations
      vary widely with most patients having some respiratory problems. Though
      extrapulmonary sarcoidosis is no longer rare, sarcoidosis involving the lacrimal
      sac is an infrequently-reported problem. We present a case of sarcoidosis
      involving the lacrimal sac in a 42-year-old Malay woman who presented with
      epiphora. She was successfully treated with steroids and dacryocystorhinostomy.
      There was no evidence of systemic involvement. It is suggested that in an unusual
      presentation of sarcoidosis, a thorough search should be made for localisation of
      other sites, lungs in particular, even in the absence of respiratory complaints.

PMID- 17538740
TI  - Gastric variceal bleed in a patient without liver cirrhosis: an unusual cause of
      haematemesis.
AB  - Tumours of the pancreas presenting as haematemesis are rare entities, with scarce
      documentation in literature. We report a 50-year-old woman who presented with
      haematemesis secondary to gastric fundal variceal bleeding due to splenic vein
      occlusion by a large mucinous cystadenoma of the pancreas. We also review the
      literature pertaining to unusual pathologies presenting as haematemesis.

PMID- 17538741
TI  - Postpartum pneumomediastinum.
AB  - A 21-year-old primigravida with previous history of pulmonary tuberculosis had a
      normal but assisted vaginal delivery after a prolonged second stage. Within 12
      hours, she complained of dyspnoea and was found to have abnormal neck and
      anterior chest wall swelling. A diagnosis of subcutaneous emphysema was made and
      this was confirmed with the chest radiograph, which also revealed
      pneumomediastinum. She recovered well within four days with conservative
      treatment.

PMID- 17538742
TI  - Post-varicella myasthenia gravis.
AB  - Myasthenia gravis is an autoimmune disease of neuromuscular junctions. We report
      a three-year-old boy with post-varicella myasthenia gravis. This patient, to the
      best of our knowledge, is the youngest in age and second reported case of the
      condition. The patient presented with drooping of both eyelids which increased as
      the day progressed, two weeks after varicella infection. Repetitive nerve
      stimulation tests showed decremental response in action potential, and the child
      responded dramatically to test doses of neostigmine. A diagnosis of post
      varicella myasthenia gravis was made and the patient was started on oral
      pyridostigmine. He is doing well at follow-up and there is no recurrence of
      symptoms to date.

PMID- 17538743
TI  - Anomalous coronary arteries and sudden death: time for action.

PMID- 17538744
TI  - Neurogenic fever.
AB  - Fever in patients with severe head injury is a commonly-encountered diagnostic
      and management problem. Neurogenic fever (NF) is a non-infectious source of fever
      in the patient with head injury and, if untreated, can cause damage to the brain
      in many ways. Until recently, NF was thought to be a relatively rare consequence
      of traumatic brain injury (TBI), but other studies have reported that four to 37
      percent of TBI survivors experience this sequela. Patients with TBI are
      immunocompromised to a certain extent and this predisposes them to sepsis, which
      should be a primary concern particularly in comatose patients. NF is essentially
      a diagnosis of exclusion. It is only when sepsis is excluded, can we consider NF.
      Though in the acute phase of severe TBI, brain temperature is indeed higher than
      the core temperature, but that significance is uncertain with regard to outcome
      prediction, since there has been a paucity of work on the use of direct methods
      of brain temperature monitoring. In summary, the pathophysiology and management
      of NF is not well understood and needs more research and understanding for better
      management and a favourable outcome.

PMID- 17538745
TI  - Renal tumours: a common incidental finding.

PMID- 17538746
TI  - Seroprevalence of hepatitis C in intravenous opioid users presenting in the early
      phase of injecting drug use in Singapore.
AB  - INTRODUCTION: All over the world, Hepatitis C virus (HCV) accounts for an
      estimated 130 million chronic infections. Injection drug use has become one of
      the most important risk factors for HCV, and within the injection drug user
      population, the prevalence of HCV antibody ranges from 70 to 95 percent depending
      on an individual's length of use and the prevalence of infection in the
      community. This study was undertaken to determine the prevalence of and the risk
      factors for Hepatitis C antibodies in injecting drug users presenting to the
      Community Addictions Management Programme (CAMP) in Singapore. METHODS:
      Eligibility criteria for inclusion in this study were all intravenous
      buprenorphine users presenting to CAMP. 106 subjects, who consented to the study,
      completed an interviewer-administered questionnaire, and underwent a urine and
      blood analysis. RESULTS: The prevalence rate for HCV was 42.5 percent among the
      subjects included in our study. The odds of seroprevalence in those sharing
      needles were 5.6 times that of those who were not, and the odds of seroprevalence
      among those using with others (peers or partners) were 6.3 times, as compared to
      among those who were individual users. Racial differences were also seen, but
      these could be accounted for by the sharing of needles. CONCLUSION: This study
      provides important local data at the onset of an early buprenorphine-injecting
      epidemic in Singapore. This data is useful for disease prevention and healthcare
      planning.

PMID- 17538747
TI  - Use of psychoactive drugs among patients visiting outpatient clinics in Karachi,
      Pakistan.
AB  - INTRODUCTION: This study was conducted to determine the proportion of usage of
      psychoactive drugs, and to identify factors associated with its use among
      patients visiting outpatient clinics of a tertiary care hospital in Karachi,
      Pakistan. METHODS: A cross-sectional study was conducted involving 461 adult (age
      18 years and above) patients, who were surveyed by using interviewer-administered
      questionnaires. All interviews were conducted by a medical students. Out of the
      total number of participants, 242 (52.5 percent) were males and 219 (47.5
      percent) were females. RESULTS: In all, 118 (25.6 percent) of the respondents
      were using some sort of psychoactive drugs, however, only 20 (4.3 percent) study
      subjects were diagnosed with any psychiatric illness. Factors found to be
      significantly associated with usage of psychoactive drugs included belonging to
      the female gender (p-value equals 0.019), older (more than 50 years) age (p-value
      is less than 0.001), being married (p-value equals 0.004), having formal
      schooling of up to 12 years (p-value equals 0.001) and physical inactivity (p
      value equals 0.004). In addition, those whose family members were using
      psychoactive drug(s) or who suffered from non-communicable diseases were more
      likely to use psychoactive drugs in comparison to others (p-value is less than
      0.001). CONCLUSION: The use of psychoactive drugs is quite common in our patients
      regardless of having any psychiatric disease. Efforts are required to control and
      prevent the abuse of these drugs. Education and awareness programmes for doctors
      and patients may help to prevent the inappropriate use of psychoactive drugs.
      Regulatory intervention to control use of these drugs is also recommended.

PMID- 17538748
TI  - Growth hormone deficiency and supplementation at in-vitro fertilisation.
AB  - INTRODUCTION: This study aims to evaluate the differences in oocyte stimulation,
      endometrial thickness, fertilisation rate and embryo quality at in-vitro
      fertilisation (IVF) in patients with documented growth hormone (GH) deficiency,
      after GH supplementation. METHODS: This was a retrospective analysis of 20 cases
      of patients who were pregnant and had GH supplementation during IVF at the
      Singapore General Hospital between 1993 and 2003. All these patients had
      previously failed IVF due to poor stimulation, poor egg quality, poor
      fertilisation at intracytoplasmic sperm injection (ICSI) or failed implantation,
      and they had documented GH deficiency. These initial cycles were compared with
      their subsequent IVF cycles with GH supplementation. A non-parametric test was
      used for statistical analysis. RESULTS: Embryo quality, determined by scoring the
      embryos on Day two using morphology, improved significantly after supplementation
      of GH (p-value is less than 0.001, median embryo score increased from 10.7 to
      16). There was also a statistically significant increase in the fertilisation
      rate for those patients who had ICSI. There was no statistical difference in the
      number of oocytes retrieved or in the mean endometrial thickness with GH.
      CONCLUSION: This study implies that GH supplementation may improve embryo quality
      in selected patients with GH deficiency. Its role in improving fertilisation rate
      at ICSI merits further research and evaluation.

PMID- 17538749
TI  - Sixty-minute post-Synacthen serum cortisol level: a reliable and cost-effective
      screening test for excluding adrenal insufficiency compared to the conventional
      short Synacthen test.
AB  - INTRODUCTION: Previous studies have indicated that most individuals reach peak
      cortisol levels in 60 minutes during the short Synacthen test (SST) done to
      exclude adrenal insufficiency. Therefore, measuring serum cortisol at only 60
      minutes may suffice. This study was carried out to evaluate the significance of
      the 60-minute serum cortisol level in SST as a reliable and cost-effective
      screening test in comparison to the conventional SST. METHODS: A cross-sectional
      study was conducted from January 2000 to September 2004, in which data was
      collected by reviewing medical records of all patients who underwent SST at the
      Aga Khan University Hospital, Karachi. A total of 236 patients suspected of
      having adrenal insufficiency were included. Values of serum cortisol at baseline,
      30 and 60 minutes post-250 ug-injection Synacthen were recorded. The cortisol
      level was measured through fluorescence polarisation immunoassay. The cut-off
      value of 20 ug/dL was used to differentiate normal individuals from hypoadrenal
      individuals. RESULTS: Out of 236 study participants, 93 (39 percent) were males
      and 143 (61 percent) were females. The mean age and standard deviation was 44.4
      +/- 21 years. Cortisol concentration increased significantly from baseline to 30
      minutes and 60 minutes after injecting Synacthen (p-value is less than 0.001 for
      each). The majority of the patients reached the cortisol peak of greater than 20
      ug/dL (555 nmol/L) at 60 minutes. Normal responses were found in 148 patients
      (63.1 percent) at both 30 and 60 minutes, while 27 participants (12 percent)
      reached a peak greater than 20 ug/dL (555 nmol/L) at 60 minutes but were less
      than 20 ug/dL (555 nmol/L) at 30 minutes. In the deficient cases, SST showed
      abnormal responses in 60 cases (25 percent) at both 30 and 60 minutes. However,
      there was only one patient who reached a peak value of 21 ug/dL (589 nmol/L) at
      30 minutes, which reduced to 17 ug/dL (485 nmol/L) at 60 minutes. CONCLUSION:
      This study showed that a 60-minute cortisol value during SST was reliable enough
      in identifying normal subjects for excluding adrenal insufficiency, and was
      equally effective in identifying abnormal cases, as compared to values at both 30
      and 60 minutes. It is therefore suggested that a single 60-minute post-Synacthen
      serum cortisol level may suffice, as compared to the conventional SST. This is
      also significant as a cost-effective measure, especially in third world countries
      where cost is a major issue for diagnosing and treating patients.

PMID- 17538750
TI  - Management of adult choledochal cyst.
AB  - INTRODUCTION: Choledochal cyst is a rare benign biliary disease mostly presenting
      during childhood. Adult presentation is rare and associated diseases and
      complications are common. This paper aims to review the management of adult
      patients who presented to our institution with choledochal cyst, focusing on
      their presentation, preoperative investigations, surgical treatment given and
      postoperative course. METHODS: A retrospective review of all our choledochal cyst
      patients from January 2000 to August 2004 was performed. Data collected included
      demographics and clinical information. RESULTS: There were ten patients, eight
      female (80 percent) and two male (20 percent). The average age at presentation
      was 38.6 (range 16-81) years. The commonest presenting complaints were
      obstructive biliary disease (nine out of ten, 90 percent). There were seven Type
      I (70 percent), one type IVA (10 percent), one type IVB (10 percent) and one (10
      percent) with Caroli's disease. Two patients had concomitant cholangiocarcinoma
      (20 percent). Three patients had associated cystolithiasis and one patient had
      pancreatitis. One patient had early cirrhosis due to her disease. Six patients
      underwent total cyst excision with a Roux-en-Y hepaticojejunostomy. One patient
      who previously had a biliary bypass underwent further resection of her cyst and
      Whipple's operation because of development of cholangiocarcinoma in the distal
      remnant cyst. They are currently well with no surgical complications. The average
      length of follow-up was 16 months (range six months to three years). CONCLUSION:
      Adult patients with choledochal cyst have associated biliary problems such as the
      presence of cholangiocarcinoma, cystolithiasis, cholecystitis and liver cirrhosis
      with portal hypertension. They tend to present similar to obstructive biliary
      disease. The best surgical option for these patients is a total cyst excision
      together with a Roux-en-Y hepaticojejunostomy.

PMID- 17538751
TI  - Efficacy of community-based multidisciplinary disease management of chronic heart
      failure.
AB  - INTRODUCTION: A multidisciplinary disease management (DM) programme in chronic
      heart failure (CHF) improves clinical outcome. The efficacy of such a programme
      in a heterogeneous Asian community is not well established. Therefore, we
      undertook the evaluation of the efficacy of the multidisciplinary community-based
      DM CHF programme. METHODS: This was a prospective study involving 154 patients
      (54 percent male) with a primary diagnosis of CHF, New York Heart Association
      functional class III/IV CHF, with left ventricular ejection fraction (LVEF) less
      than 40 percent. The mean age was 65 +/- 12 years and mean LVEF was 27 +/- 9
      percent. We evaluated CHF hospitalisation, quality of life, activity status and
      quality of care (percentage of patients who received ACE inhibitors/angiotensin
      receptor blockers (ARB) and beta blockers after a period of six months. RESULTS:
      At six months, there was improvement in the quality of life and activity status
      (p < 0.001). ACE inhibitors/ARB were maintained in 97 percent of the patients and
      there was an increased usage of beta blockers (p-value equals 0.001). The rate of
      CHF hospitalisation was reduced by 68 percent (p-value is less than 0.001) and
      there was no mortality. CONCLUSION: The multidisciplinary DM of CHF in a
      heterogeneous Asian community showed significant improvement in quality of life,
      quality of care and reduction in CHF hospitalisation.

PMID- 17538752
TI  - Lack of clinical usefulness of interleukin-6 in long-term follow-up of acutely
      decompensated heart failure.
AB  - INTRODUCTION: Interleukin-6 (IL-6) has been identified as a predictor of death,
      new heart failure (HF) episodes and need for heart transplantation in patients
      with advanced HF. The aim of this study was to examine the relationship between
      plasma IL-6 levels in patients with decompensated HF and either survival or new
      admissions due to HF. METHODS: We studied 111 patients admitted due to
      decompensated HF. Long-term survival was assessed from the day of admission to
      the hospital to the day of death or new admissions due to HF. RESULTS: The mean
      IL-6 concentration was 90 +/- 115 pg/ml (range 1.5-743 pg/ml). There were no
      differences in IL-6 concentration with regard to age, gender and cause of HF. At
      the end of follow-up period, 22 patients (20 percent) had died due to causes
      related to HF and 54 patients (48 percent) had been readmitted to the hospital
      due to new HF episodes. Using regression analyses, serum IL-6 levels were not
      identified as a prognostic factor. Systolic dysfunction, previous diagnosis of HF
      and diabetes mellitus were independent predictors of death. CONCLUSION: These
      findings suggest that a single measurement of serum IL-6 in patients with
      decompensated HF lacks clinical usefulness in long-term follow-up.

PMID- 17538753
TI  - Diastolic function abnormalities in rheumatoid arthritis: relation with duration
      of disease.
AB  - INTRODUCTION: There are limited studies on the prevalence of diastolic
      dysfunction in rheumatoid arthritis (RA) from the Indian subcontinent. The aim of
      this study was to evaluate left ventricular filling abnormalities in patients
      with RA without clinically-evident cardiovascular manifestations, and to
      correlate it with disease duration. METHODS: 45 patients affected with RA
      according to the American Rheumatism Association criteria, were selected without
      evidence of cardiac disease, and compared with age- and sex-matched control
      subjects. All patients and the control group were submitted to M-mode, two
      dimensional and Doppler echocardiography. The following diastolic parameters were
      evaluated: peak of early diastolic (E) and late diastolic (A) mitral flow
      velocity, E/A ratio, isovolumic relaxation time (IVRT), ejection fraction and
      fractional shortening. RESULTS: In RA patients, left ventricular filling
      abnormalities were found characterised by a reduced E/A ratio (mean [SD] 0.98
      [0.22] versus controls 1.09 [0.11]; p-value equals 0.004), prolonged IVRT (75.77
      [8.12] ms versus 70.43 [2.94] ms; p-value equals 0.001) and increased late
      diastole flow velocity (76.91 [11.61] cm/s versus 70.11 [5.32] cm/s; p-value
      equals 0.001). In the group of patients, a negative correlation was found between
      E/A ratio and disease duration (Pearson correlation, r equals -0.56, p-value
      equals 0.001), indicating diastolic dysfunction with increasing disease duration.
      A strong correlation was also found between IVRT and disease duration (r equals
      0.66, p-value equals 0.01) and also between late diastolic flow velocity and
      disease duration (r equals 0.61, p-value equals 0.001). CONCLUSION: The present
      study confirms a high frequency of left ventricular diastolic dysfunction
      characterised by impaired E/A ratio, prolonged IVRT and increased late diastole
      flow velocity in patients with RA without evident cardiovascular disease. The
      correlation between transmitral flow alteration and disease duration suggests a
      subclinical myocardial involvement with disease progression. This may be relevant
      to the high incidence of cardiovascular deaths observed in patients with RA.

PMID- 17538754
TI  - Impact of household hygiene and water source on the prevalence and transmission
      of Helicobacter pylori: a South Indian perspective.
AB  - INTRODUCTION: In developing countries, the Helicobacter pylori (H. pylori)
      infection rate is high, especially in lower socioeconomic groups. The populace in
      developing countries lives in conditions that are highly conducive to the
      acquisition of microorganisms. Poor hygiene, crowded household conditions and
      deficient sanitation mark their day-to-day life. We aimed to find out the roles
      of household hygiene and water source in the prevalence and transmission of H.
      pylori infection among the South Indian population using polymerase chain
      reaction (PCR) assay. METHODS: The selected population consisted of 500 adults of
      varying ages ranging from 30 to 79 years, with upper gastrointestinal tract
      symptoms. Each participant in the study was given a questionnaire to complete.
      Samples to assess H. pylori infection included three gastric biopsies (two from
      the antrum and one from the corpus region). Infection was detected by PCR
      amplification of the 16S rRNA gene of H. pylori. The data was then examined
      statistically by univariate and multivariate analyses. RESULTS: The overall
      prevalence of H. pylori was detected to be 80 percent. Prevalence increased with
      an increase in age and it was found to be 90 percent in the 70-79 year age group
      (p-value is less than 0.01). The prevalence of infection among people who drank
      water from wells was 92 percent compared with 74.8 percent of those who drank tap
      water (p-value is less than 0.001). H. pylori infection prevalence was found to
      be higher in people with low clean water index (CWI) (88.2 percent) than in those
      with higher CWI (33.3 percent) (p-value is less than 0.001). While the prevalence
      of H. pylori in the subjects with lower socioeconomic status was 86.1 percent, in
      higher groups, it was 70 percent (p-value is less than 0.001). The prevalence of
      H. pylori was also found to be higher in subjects who lived in overcrowded
      houses. It was 83.7 percent with high crowding index, 76.6 percent with medium
      crowding index, and 71.3 percent with low crowding index (p-value is less than
      0.05). CONCLUSION: The results of the present study suggest that the risk of
      acquisition and transmission of H. pylori can be prevented to a large extent by
      following improved household hygienic practices, proper waste disposal measures
      as well as the regular use of boiling water for drinking purposes.

PMID- 17538755
TI  - Cytogenetic and clinical profile of Down syndrome in Northeast Malaysia.
AB  - INTRODUCTION: This study was designed to evaluate the karyotype pattern, clinical
      features and other systemic anomalies of patients with Down syndrome in Malaysia.
      METHODS: Retrospective analysis was performed on the case records of 149 patients
      confirmed as Down syndrome by cytogenetic analysis at Human Genome Centre and
      Genetic Clinic at the Universiti Sains Malaysia. RESULTS: Among the 149 cases of
      Down syndrome presenting over a period of 4.2 years, free trisomy (non
      disjunction) was present in 141 cases (94.6 percent). One case (0.7 percent) had
      translocation, and seven cases (4.7 percent) were mosaics. Average age at
      presentation was 10.6 months. Average maternal age at birth of the affected child
      was 32.3 years. The prominent craniofacial features noted were upslanting
      palpebral fissures (89.3 percent), flat facial profile (64.9 percent), low set
      ears (56.1 percent), epicanthic folds (17.5 percent) and protruding tongue (19.2
      percent). A total of 52.6 percent of the cases had documented hypotonia.
      Characteristic limb and dermatoglyphic anomalies included short stubby fingers
      (24.5 percent), sandal gap (33.3 percent), unilateral or bilateral simian crease
      (36.8 percent) and clinodactyly (19.2 percent). Ophthalmological abnormalities,
      such as hypertelorism, were presented in 33.3 percent of the cases. Congenital
      heart disease was diagnosed in 35 out of 71 cases (49.3 percent) and
      gastrointestinal anomalies were noted in 18 out of 79 cases (22.7 percent)
      analysed. CONCLUSION: Efforts to establish early diagnosis and a proper screening
      for high association with systemic anomalies should be undertaken among the Down
      syndrome patients in this population.

PMID- 17538756
TI  - Oral triiodothyronine in the perioperative management of central hypothyroidism.
AB  - Oral triiodothyronine (T3) has never been described in literature as a major form
      of perioperative therapy. This series highlights the role of oral
      triiodothyronine in the perioperative management of patients with overt
      hypothyroidism for semi-urgent surgeries. We describe 12 patients with central
      hypothyroidism occurring secondary to pituitary tumours manifesting with severe
      neurological symptoms that required early surgical intervention. These patients
      were managed without any significant complications by administering perioperative
      oral triiodothyronine.

PMID- 17538757
TI  - Awareness, knowledge and attitude toward informed consent among doctors in two
      different cultures in Asia: a cross-sectional comparative study in Malaysia and
      Kashmir, India.
AB  - INTRODUCTION: Informed consent is now accepted as the cornerstone of medical
      practice, with reasonable patient standards typically considered to be
      appropriate in the developed countries; however it is still challenged in many
      developing countries. The objective of this descriptive study was to evaluate the
      perceptions and practices among attending medical professionals in matters
      relating to informed consent in selected hospitals. METHODS: A questionnaire
      based cross sectional survey among doctors in the two tertiary care hospitals,
      one in Malaysia and the other in Kashmir, was performed. RESULTS: Awareness on
      informed consent was universal with "reasonable physician standard" as the most
      popular choice. As compared to doctors in Malaysia, doctors from Kashmir showed a
      tendency to reservedly disclose medical information (p-value equals 0.051) and
      withhold it, if it was deemed potentially harmful (p-value is less than 0.001) or
      requested so by relatives (p-value is less than 0.023). They also withheld some
      information from female patients (p-value is less than 0.001). When consent was
      refused despite needing lifesaving intervention, the majority of both respondents
      (73 percent versus 80 percent) considered intervention without consent to be
      justified. Respondents from Malaysia felt that parents could refuse treatment on
      their children's behalf on the basis of their beliefs (p-value is less than
      0.001). CONCLUSION: Despite a very high awareness of informed consent, the model
      chosen reflected age-old medical paternalism. Doctors' opinions are accorded a
      larger role in clinical decision-making in Kashmir. The results emphasise the
      need for doctors to change their attitude and acknowledge the patient's autonomy,
      which is the basis of modern medical ethics, and yet still be aware of the
      cultural and religious views of the local population.

PMID- 17538758
TI  - Clinically-relevant variations of the carotid arterial system.
AB  - INTRODUCTION: Developmental anomalies in the origin and branching pattern of the
      external carotid artery are not common. The level of the bifurcation of the
      common carotid artery and also the variations in the origin/branching pattern of
      the external carotid artery are well known and documented. METHODS: The
      variations in the level of bifurcation of the common carotid artery and the
      branching pattern of the external carotid artery were studied on 95 cadavers (52
      male and 43 female). The common, external and internal carotid arteries were
      dissected on both sides. The level of carotid bifurcation was determined by
      comparison with the cervical vertebrae. Branching patterns of the carotid
      arteries were examined. RESULTS: Apart from the textbook description of the
      arteries, we came across several interesting variations. The bifurcation level of
      the common carotid artery was determined to be 50 percent at the C3 level, 40
      percent at the C4 level and ten percent at the C2 level on the right side, and 55
      percent at the C3 level, 35 percent at the C4 level, one percent at the C5 level
      and nine percent at the C2 level on the left side. CONCLUSION: Anatomical
      knowledge of the origin, course, and branching pattern of the external carotid
      artery, as well as the level of bifurcation of the common carotid artery, will be
      useful to surgeons when ligating the vessels in the head and neck regions during
      surgery and to avoid unnecessary complications during carotid endarterectomy.

PMID- 17538759
TI  - Sudden death due to single coronary artery.
AB  - Coronary artery anomalies that entail a risk of sudden death are frequently
      associated with complex cardiac malformations but may occasionally be solitary. A
      31-year-old man became ill in the night and lost consciousness. He was taken to a
      hospital where he was treated. However, he died on the same day. The death was
      considered to be suspicious and an autopsy was mandated. On macroscopic
      examination, the heart weighed 410 g. A single coronary artery that originated
      from the right aortic sinus was found. The coronary artery ostium was 0.8 cm in
      diameter and had a hole-like shape. Demonstration of coronary artery pathologies
      in autopsies is vital for the elucidation of sudden death cases related to these
      lesions and for the development of new treatment approaches. The aims of this
      case report are to contribute to a better understanding of the coronary artery
      anomalies and emphasise their medicolegal importance.

PMID- 17538760
TI  - Sudden death related to anomalous origin of coronary artery and coexisting
      fenestrated membrane of the sinus coronarius.
AB  - Coronary artery anomalies that may be an isolated defect or part of complex
      congenital malformations of the heart are also often associated with a high risk
      of sudden death. A 19-year-old woman lost consciousness in the night. She was
      taken to hospital where she was treated. However, she died on the same day. The
      prosecutor considered the death suspicious, and the victim was taken to the
      morgue department for further examination and autopsy. On macroscopical
      examination, both coronary arteries originated from the left aortic sinus with
      the left one being dominant. The orifice of the sinus coronarius in the right
      atria was covered with a fenestrated membrane. Demonstration of coronary artery
      pathologies and associated anomalies in autopsies is vital for the elucidation of
      sudden death cases related to these lesions and for the development of new
      treatment approaches. The purposes of this case report are to characterise and
      identify markers of the coronary artery anomalies and to highlight their
      medicolegal importance in sudden death cases.

PMID- 17538761
TI  - Diabetic fibrous mastopathy.
AB  - Diabetic fibrous mastopathy is reported in a 37-year-old premenopausal woman. A
      known case of insulin-dependent diabetes mellitus, she presented with bilateral
      hard breast lumps, which were suggestive of malignancy on both ultrasonography
      and mammography. Fine-needle aspiration cytology and core biopsy showed fibrosis.
      An incisional biopsy further excluded malignancy and was conclusive for diabetic
      fibrous mastopathy.

PMID- 17538762
TI  - Nimesulide-induced hepatotoxicity and fatal hepatic failure.
AB  - Non-steroidal anti-inflammatory drugs (NSAIDs) and cyclo-oxygenase-2 (cox-2)
      inhibitors are structurally heterogeneous drugs that share similar therapeutic
      actions and adverse effects. Hepatotoxicity, although a relatively rare adverse
      effect of this class of drugs, can be severe. This has led to the withdrawal of
      some NSAIDs from the market. Nimesulide is an NSAID, with cox-2 preference, which
      has been reported to cause death from hepatic failure. However, most reports have
      been from European countries. Asian reports include that from Israel and India.
      We report three patients who presented with acute hepatitis after being
      prescribed nimesulide, one of whom died from fulminant hepatic failure.

PMID- 17538763
TI  - Electrocardiographical case. Asymptomatic patient with deep T-wave inversions.
AB  - A 45-year-old man was found to have an abnormal myocardial perfusion scan. He was
      asymptomatic, with no chest pain, breathlessness or palpitations. Clinical
      examination was unremarkable. The 12-lead electrocardiography (ECG) showed
      increased QRS voltage in leads V3-V6, and deep T-wave inversions noted in leads
      V3-V6, with an absence of septal Q waves. These ECG features were characteristic
      of apical variant hypertrophic cardiomyopathy (HCM). He underwent a coronary
      angiogram that revealed normal coronary arteries, and a left ventriculogram which
      showed apical HCM. Transthoracic echocardiography further confirmed the
      diagnosis. No drug therapy was instituted as he was asymptomatic. Apical HCM is
      discussed.

PMID- 17538765
TI  - Hazards of complementary and alternative medicine.

PMID- 17538767
TI  - Comparative evaluation of obesity measures: relationship with blood pressures and
      hypertension.

PMID- 17538769
TI  - Nogo A protein neutralisation and motor cortex computer implants: a future hope
      for spinal cord injury.

PMID- 17538770
TI  - Gene frequencies of human platelet alloantigens in Kelantan, Malaysia.

PMID- 17538771
TI  - Use of cefepime for the treatment of infections caused by extended spectrum: beta
      lactamase-producing Klebsiella pneumoniae and Escherichia coli.

PMID- 17538774
TI  - Role of zinc in ALS.
AB  - The causes of amyotrophic lateral sclerosis (ALS) are poorly understood. A small
      proportion, about 2%, is associated with a mutation in the superoxide dismutase
      (SOD1) gene, and mice expressing this mutant gene exhibit a progressive, ALS-like
      neurodegenerative disease. Studies of these animals, as well as of human post
      mortem tissue, reveal the presence of multiple pathological processes, including
      oxidative stress, glutamate excitotoxicity, neuroinflammation, mitochondrial
      degeneration, alterations in neurofilaments and neurotubules, mitochondrial
      damage, aggregation of proteins, abnormalities in growth factors, and apoptosis.
      We propose that alterations in the disposition of zinc ions may be important in
      the initiation and development of ALS. SOD1 binds zinc, and many of the mutant
      forms of this enzyme associated with ALS show altered zinc binding. Alterations
      in the expression of metallothioneins (MTs), which regulate cellular levels of
      zinc, have been reported in mutant SOD1 mice, and deletion of MTs in these
      animals accelerates disease progression. Zinc plays a key role in all the
      pathological processes associated with ALS. Our zinc hypothesis also may help
      explain evidence for environmental factors in some cases of ALS, such as in the
      Chamorro tribe in Guam and in the Gulf War.

PMID- 17538775
TI  - Association of polymorphisms in vascular endothelial growth factor gene with the
      age of onset of amyotrophic lateral sclerosis.
AB  - This study investigated the association between polymorphisms in vascular
      endothelial growth factor (VEGF) gene (-1558C-T, -1190A-G and -1154A-G) and age
      at onset of amyotrophic lateral sclerosis (ALS). Between July 2000 and June 2004
      we conducted a clinical genetic study at Peking University Third Hospital, China.
      The analyses included a total of 93 ALS patients. Genotyping was performed by
      using the 5'-nuclease assay technology (Applied Biosystems) with TaqMan allele
      specific fluorogenic oligonucleotide probes. We used multivariate linear
      regression modelling and haplotype-based association test to analyse the
      association of VEGF gene polymorphisms with the age of onset, adjusting for
      initial symptoms and sex. The results indicated that patients with the -1190A/G
      and -1190G/G genotypes exhibited about a 4.1- and 9.4-years earlier onset of ALS
      than the patients with the -1190A/A genotype. A similar pattern emerged when the
      VEGF -1154A-G gene was considered: the beta was -7.9(p<0.001) years and 
      11.7(p<0.001) years for -1154A/G and -1154G/G genotypes, respectively. The VEGF 
      1558C-T had a positive effect in the -1558C/T group (p = 0.007, beta = 7.0) and 
      1558T/T (p<0.001, beta = 9.6) compared to the -1558C/C group. We neither observed
      an interaction nor haplotype association with age onset among -1558C-T, -1190A-G
      and -1154A-G. In conclusion, our results indicate, for the first time, that there
      was an important association between the polymorphism of the VEGF gene and age of
      ALS onset. This suggests a possible role for VEGF variability in the aetiology of
      individual differences in ALS onset.

PMID- 17538776
TI  - The role of exogenous risk factors in amyotrophic lateral sclerosis in Wakayama,
      Japan.
AB  - The incidence of ALS in Wakayama Prefecture has been markedly higher than that
      elsewhere in the world. Recently, however, the incidence has gradually decreased,
      especially in men, and the age at onset has shifted to the elderly, indicating
      the possible role of exogenous factors in the development of ALS. To evaluate
      factors related to the disease, we conducted a retrospective study. This study
      examined 108 patients with definite ALS diagnosed according to El Escorial
      criteria and 302 neurological controls (older than 40 years old) consecutively
      admitted to Wakayama Medical Hospital between 1999 and 2004. Having past history
      of cervical spondylosis or spinal spondylotic myelopathy (CS/SSM) with/without
      surgical treatment, cervical MRI findings, history of bone fracture, and
      occupation at onset were compared between the ALS patients and the neurological
      controls. Among 108 ALS patients, 45.4% had past history of CS/SSM compared to
      19.4% of the neurological controls (p<0.0001, OR: 3.725, 95% CI 2.173-6.387).
      Among the ALS patients, 13% had had surgical treatment for CS/SSM, which was
      significantly higher than the 4.3% of the neurological controls (p<0.003, OR:
      4.333, 95% CI 1.647-11.401). Cervical MRI findings were classified into four
      grades according to the severity of canal narrowing and compression of the spinal
      cord. Regarding cervical MRI findings, the percentage of ALS patients who showed
      canal narrowing and compression of the spinal cord was significantly higher than
      that of the controls (ALS: 72.0%, the controls: 29.5%, OR: 4.799, 95% CI 2.65
      8.70). Comparison of the occupation at disease onset revealed that primary and
      secondary industrial occupations significantly increased the risk of ALS (2.69,
      95% CI 1.40-5.16, 2.81, 95% CI 1.45-5.46, respectively). Conversely, tertiary
      industrial occupations significantly decreased the risk of ALS (age- and sex
      adjusted OR: 0.54, 95% CI 0.30-0.98). In conclusion, CS/SSM, surgical treatment
      for CS/SSM and occupation at onset are suspected to be risk factors for
      developing/triggering or worsening ALS.

PMID- 17538777
TI  - Effect of non-steroidal anti-inflammatory medications on the risk of amyotrophic
      lateral sclerosis.
AB  - Inflammatory processes may be involved in the pathogenesis of amyotrophic lateral
      sclerosis (ALS). We examined the association of non-steroidal anti-inflammatory
      drugs (NSAIDs) with the risk of ALS in case-control study of incident cases (n =
      111) conducted within the Kaiser Permanente Medical Care Program of Northern
      California during the years 1996-2000. Controls (n = 258) randomly selected from
      the same population were frequency matched by age and gender to the ALS cases.
      Information regarding use of NSAIDs (non-aspirin and aspirin) and three classes
      of 'control' medications was collected by in-person structured interview.
      Subjects who used medication at least twice a week for at least a month were
      classified as 'ever users'. Multivariable logistic regression models were
      adjusted for age, gender, history of osteoarthritis/rheumatoid arthritis and
      pain, and other medication use. Overall, there was no association between NSAID
      use and ALS; however, some sex differences were noted for non-aspirin NSAID use.
      Among men, non-aspirin NSAID use was associated with a two-fold increased risk of
      ALS (adjusted odds ratio (OR) 2.0, 95% confidence interval (CI) 1.0-3.9), whereas
      among women, non-aspirin NSAID use was not associated with increased ALS risk
      (adjusted OR 0.5, 95% CI 0.2-1.2). ALS risk was not associated with aspirin use
      or with 'control' medications. This study did not find any evidence to suggest
      that NSAID use reduces the risk of ALS. The observed sex differences with non
      aspirin NSAID use could be due to chance or an unmeasured confounder.

PMID- 17538778
TI  - Perceptions of quality of life in people with ALS: effects of coping and health
      care.
AB  - Few qualitative studies have explored the 'meaning' of life experiences for
      persons with ALS. We aimed to identify the meaning of QoL in five selected
      individuals, and to consider how their experience of health care affected
      perceived well-being, using a phenomenological approach. Four of the five
      participants were revisited. Themes that emerged included: importance of faith,
      search for control, importance of dignity, desire to maintain identity,
      importance of family, a sense of loss, importance of altruism and support,
      fighting amyotrophic lateral sclerosis, and appreciation of life. All
      participants felt that professional services contributed to their well-being. QoL
      remained individual and multi-dimensional and was defined by cognitive and
      behavioural strategies used to cope with ALS. Our findings highlight the need to
      consider how persons with ALS may adapt to progressive illness.

PMID- 17538779
TI  - Quantitative assessment of motor fatigue: normative values and comparison with
      prior-polio patients.
AB  - Motor fatigue is a common complaint of polio survivors and has a negative impact
      on activities of daily living. The aim of this study was to establish a normative
      database for hand grip strength and fatigue and to investigate differences
      between prior-polio subjects and normal controls. Static and dynamic hand grip
      fatigue and maximum voluntary isometric contraction (MVIC) of hand grip were
      measured in subjects with a prior history of polio (n = 44) and healthy controls
      (n = 494). A normative database of fatigue was developed using four indices of
      analysis. Compared with healthy controls, subjects with prior polio had
      significantly reduced hand grip strength but developed greater hand grip fatigue
      in only one fatigue index. Quantitative measurement of fatigue in the prior-polio
      population may be useful in order to detect change over time and to evaluate
      treatment strategies.

PMID- 17538780
TI  - Three soccer playing friends with simultaneous amyotrophic lateral sclerosis.
AB  - Amyotrophic lateral sclerosis is a neurodegenerative disease of largely unknown
      cause, predominantly affecting upper and lower motor neurons. A recent study in
      Italy suggested an increased incidence of ALS among professional Italian soccer
      players. We report a cluster of three amateur league soccer players who were
      friends from the same part of southern England, and developed ALS simultaneously.
      This might suggest that keen amateur soccer players are also at risk.

PMID- 17538781
TI  - Respiratory apraxia in amyotrophic lateral sclerosis.
AB  - Respiratory dysfunction is a critical problem in amyotrophic lateral sclerosis
      (ALS). We report a patient with ALS who had respiratory apraxia. A 74-year-old
      female presented with progressive dysarthria and dysphagia. Clinical signs and
      evidence of widespread denervation on electromyography (EMG) confirmed the
      diagnosis of ALS. She had no signs of dementia. Irregular volitional inspiratory
      movements on verbal command were noticed, in contrast with rhythmic automatic
      inspiration - respiratory apraxia. Limb and buco-facial movements showed no signs
      of apraxia. EMG of respiratory muscles was normal, apart from irregular phasic
      activity of the diaphragm on volitional inspiration; this was confirmed by
      recording respiratory movements with a percutaneous sensor transducer. Sleep
      study was normal. She deteriorated rapidly; nonetheless, no clinical sign of
      dementia or other apraxic findings were observed. ALS, particularly when of
      bulbar onset, can cause respiratory apraxia and EMG of the respiratory muscles
      can be useful to detect this condition.

PMID- 17538782
TI  - Early use of non-invasive ventilation prolongs survival in subjects with ALS.
AB  - Non-invasive positive pressure ventilation (NPPV) can improve survival in ALS
      patients with advanced respiratory impairment, but it is not known if it is
      beneficial earlier in the disease course. A retrospective cohort study of
      patients with ALS was performed comparing survival from time of diagnosis in
      subjects who started NPPV use when their FVC was >or=65% predicted (Early NPPV)
      with subjects who started NPPV when their FVC was below 65% predicted (Standard
      NPPV). The Early group (n = 25) and the Standard group (n = 67) were similar
      except for pulmonary function (mean FVC in Early NPPV group = 74.3+/-10.1%
      predicted and 48.3+/-11.3 in Standard group, p<0.001). The median time from ALS
      diagnosis to death was significantly longer in the Early NPPV group (2.7 years
      vs. 1.8 years, p = 0.045). This remained significant after adjustment for
      potential confounding factors (H.R. = 0.55, 95% CI 0.31-0.98). Survival from time
      of diagnosis was nearly one year longer in the Early group. Until more definitive
      data are available from randomized trials, our findings suggest that clinicians
      either encourage earlier use of NPPV or use more sensitive tests for respiratory
      muscle impairment than upright FVC.

PMID- 17538783
TI  - Inappropriate sexual behaviour in a case of ALS and FTD: successful treatment
      with sertraline.
AB  - In a subset of patients, ALS is associated with frontotemporal dysfunction (ALS
      FTD). Clinically, ALS-FTD may present with a variable spectrum of cognitive and
      behavioural deficits. We report a 53-year-old ALS-FTD patient developing
      inappropriate sexual behaviour (ISB) manifesting as a vigorous sexual drive with
      exhausting demands for sexual intercourse and physical aggressions against his
      wife. This distressing symptom could be alleviated with the selective serotonin
      reuptake inhibitor sertraline. ISB is an embarrassing symptom for most patients
      and their caregivers and may therefore be under-reported. Since effective
      treatment is available, we suggest an open and proactive discussion of sexual
      issues in this patient group.

PMID- 17538784
TI  - Amyotrophic lateral sclerosis with sarcoidosis.

PMID- 17538786
TI  - Accurate and reliable pose recovery of distal locking holes in computer-assisted
      intra-medullary nailing of femoral shaft fractures: a preliminary study.
AB  - OBJECTIVE: One of the difficult steps in intra-medullary nailing of femoral shaft
      fractures is distal locking - the insertion of distal interlocking screws.
      Conventionally, this is performed using repeated image acquisitions, which leads
      to considerable irradiation of the patient and surgical team. Virtual fluoroscopy
      has been used to reduce radiation exposure, but can only provide multi-planar two
      dimensional projection views. In this study, two calibrated fluoroscopic images
      were used to automatically recover the positions and orientations of the distal
      locking holes (DLHs). The ultimate goal is to provide precise three-dimensional
      guidance during distal locking. METHODS: A model-based optimal fitting process
      was used to reconstruct the positions and orientations of the DLHs from two
      calibrated fluoroscopic images. No human intervention is required. A preliminary
      in vitro validation study was conducted to analyze the accuracy and reliability
      of the technique using images acquired from different viewpoints. The ground
      truths of the DLH were obtained by inserting a custom-made steel rod through the
      hole and then digitizing both the top and bottom centers of the rod using a sharp
      pointer. The recovery errors were computed by comparing the computed results to
      the ground truths. RESULTS: In all experiments, the poses of the DLHs could be
      recovered fully automatically. When the recovered positions and orientations of
      the DLHs were compared to their associated ground truths, a mean angular error of
      0.5 degrees (STD = 0.2 degrees ), and a mean translational error of 0.1 mm (STD =
      0.0 mm) were found. CONCLUSIONS: Accurate and reliable pose recovery of distal
      locking holes from two calibrated fluoroscopic images is achievable. Our
      preliminary in vitro experimental results demonstrate that the recovered poses of
      the distal locking holes are sufficiently accurate for intra-operative use.

PMID- 17538787
TI  - Design and development of a computer assisted glenoid implantation technique for
      shoulder replacement surgery.
AB  - OBJECTIVE: Replacement of the diseased shoulder joint with implants is a
      procedure whose frequency is rapidly increasing. However, glenoid replacement
      remains challenging due to the difficult joint exposure and visualization of
      anatomical reference landmarks during the procedure. Improper positioning of the
      glenoid component can lead to early failure. The objective of this study was to
      develop and evaluate a Computer Assisted Glenoid Implantation (CAGI) technique to
      achieve a more accurate and reliable placement of the glenoid component.
      MATERIALS AND METHODS: Twenty cadaveric scapulae were imaged with CT. The
      accuracy of an electromagnetic tracking system and 3D surface modeling for the
      measurement of glenoid position was compared to that of the standard CT-based
      method. Custom jigs were then developed to track instruments and to correct for
      scapular motion during in vitro trials. A standardized protocol for determining,
      in real time, the glenoid position and placement was developed and validated.
      RESULTS: The version angles measured by the tracking system, CT, and the 3D
      modeling software were 0.0 +/- 1.2 degrees , -1.3 +/- 1.0 degrees , and -1.1 +/-
      1.1 degrees , respectively. The magnitudes for inclination angles were 0.7 +/-
      0.7 degrees , 0.9 +/- 0.8 degrees , and 1.0 +/- 0.7 degrees , respectively. A
      statistically significant difference was found only between measurements made
      with the tracking system and with CT (p < 0.05). Testing of the CAGI system in a
      cadaveric trial resulted in an accuracy of 1.17 degrees of version and 0.60
      degrees of inclination. The procedure was readily performed with excellent
      feedback and guidance for the surgeon. CONCLUSIONS: Preoperative planning using
      CT imaging with 3D modeling and intraoperative tracking were combined to produce
      improved accuracy and reliability of glenoid implantation in the setting of total
      shoulder arthroplasty.

PMID- 17538788
TI  - Fluoroscopic navigation system for hip surface replacement.
AB  - Metal-on-metal hip resurfacing arthroplasties represent an alternative to total
      hip arthroplasties for young and active patients, enabling the preservation of
      intact femoral bone and therefore improving the prognosis for future hip joint
      replacements. Follow-up studies have shown that the main reasons for early
      implant failure are mal-orientation of the implant stem in relation to the
      femoral neck axis, and notching of the femoral neck during femoral head
      preparation, as well as by exposed cancellous bone after implantation. A computer
      assisted planning and navigation system for the implantation of femoral hip
      resurfacing implants has been developed which supports the surgeon during
      intraoperative fluoroscopy-based planning and navigation of implant positioning.
      This paper presents the results of a cadaver study performed to evaluate the
      system's functionality and accuracy.

PMID- 17538789
TI  - A-mode ultrasound-based intra-femoral bone cement detection and 3D reconstruction
      in RTHR.
AB  - Due to the difficulty of determining the 3D boundary of the cement-bone interface
      in Revision Total Hip Replacement (RTHR), the removal of the distal intra-femoral
      bone cement can be a time-consuming and risky operation. Within the framework of
      computer- and robot-assisted cement removal, the principles and first results of
      an automatic detection and 3D surface reconstruction of the cement-bone boundary
      using A-mode ultrasound are described. Sound propagation time and attenuation of
      cement were determined considering different techniques for the preparation of
      bone cement, such as the use of a vacuum system (Optivac, Biomet). A laboratory
      setup using a rotating, standard 5-MHz transducer was developed. The prototype
      enables scanning of bisected cement-prepared femur samples in a 90 degrees
      rotation range along their rotation axis. For system evaluation ex vivo, the
      distal femur of a human cadaver was prepared with bone cement and drilled (O 10
      mm) to simulate the prosthesis cavity in a first approximation. The sample was
      cut in half and CT scanned (0.24 mm resolution; 0.5 mm distance; 0.5 mm
      thickness), and 3D voxel models of the manually segmented bone cement were
      reconstructed, providing the ground truth. Afterwards, 90 degrees segments of
      each ex-vivo sample were scanned by the A-mode ultrasound system. To obtain
      better ultrasound penetration, we used coded signal excitation and pulse
      compression filtering. A-mode ultrasound signal detection, filtering and
      segmentation were accomplished fully automatically. Subsequently, 3D voxel models
      of each sample were calculated. Accuracy evaluation of the measured ultrasound
      data was performed by ICP matching of each ultrasound dataset ( approximately
      8000 points) to the corresponding CT dataset and calculation of the residual
      median distance error between the corresponding datasets. Prior to each ICP
      matching, an initial pre-registration was calculated using prominent landmarks in
      the corresponding datasets. This method yielded a median distance error in the
      region of 0.25 mm for the cement-bone interface in both femur halves.

PMID- 17538790
TI  - Image-free cup navigation inaccuracy: a two-study approach.
AB  - The present study tested the accuracy of an image-free navigation system used for
      total hip arthroplasty (THA). Two parallel, prospective studies were performed:
      one on real patients and the other on pelvic phantoms. We used a comparison
      between the intra-operative cup orientation, as displayed by the navigation
      system, and the post-operative cup position, as measured on CT data. The mean
      intrinsic overall error (+/- standard deviation) found in the phantom study was
      2.6 +/- 1.1 degrees (range: 1.5-4.4 degrees ) for cup abduction, and 0.9 +/- 0.7
      degrees (range: 0-2.5 degrees ) for cup anteversion. The system was less accurate
      in the clinical operative setting. The evaluation model was able to identify, and
      more importantly quantify, the clinically induced error. Ameliorating this would
      improve the clinical accuracy of the system.

PMID- 17538791
TI  - Description and validation of a navigation system for intra-operative evaluation
      of knee laxity.
AB  - This paper describes the features of KIN-nav, a navigation system specifically
      dedicated to intra-operative evaluation of knee laxity, and assesses the
      reliability of the system during surgery. The acquisition protocol for its intra
      operative use, the original user interface, and the computational methods for
      elaboration of kinematic data are described in detail. Moreover, an extensive and
      specific validation of the system was performed in order to evaluate its intra
      operative performance and usability. KIN-nav's reliability and accuracy were
      analyzed in a series of 79 patients undergoing ACL reconstruction. The intra
      surgeon repeatability computed for ACL-deficient and reconstructed knees at
      different flexion angles was less than 0.6 degrees for varus-valgus (VV)
      rotation, less than 1 mm for AP translation, and less than 1.6 degrees for IE
      rotation. The inter-surgeon repeatability is less than 2 degrees for VV rotation,
      5 degrees for internal-external rotation, and less than 3 mm for AP translation.
      The proposed method was fast (requiring an additional 10 minutes of surgical time
      on average), required only a short learning period (5 cases), was minimally
      invasive, and was robust from the numerical perspective. Our system clearly shows
      that the use of navigation systems for kinematic evaluation provides useful and
      complete information on the knee state and test performance, and is simple and
      reliable to use. The good repeatability in manual kinematic tests is an
      improvement on the present ability to discriminate knee kinematics intra
      operatively, and thus offers the possibility of better discrimination between
      knee pathologies and the prospect of new surgical applications.

PMID- 17538792
TI  - Comparison of functional results with navigation-assisted minimally invasive and
      conventional techniques in bilateral total knee arthroplasty.
AB  - This study was undertaken to compare the clinical and radiological results
      achieved using navigation-assisted minimally invasive surgery (NA-MIS) and
      conventional (CON) techniques in 42 bilateral total knee arthroplasty (TKA)
      patients with a minimum follow-up of one year. Clinical evaluations were
      performed using range of motion (ROM), Hospital for Special Surgery (HSS) scores,
      and Western Ontario and McMaster University (WOMAC) scores (pain, functional, and
      total) at 3, 6 and 9 months and one year postoperatively. Patients' subjective
      preferences and radiological indices, including mechanical axis and coronal
      inclinations of the prostheses, were compared at one year postoperatively. NA-MIS
      TKA yielded better HSS and WOMAC total scores than CON TKA up to six months, and
      a better WOMAC pain score up to 9 months. However, these differences were not
      significant at one year postoperatively. ROM was comparable in both groups at all
      times, but more patients preferred the NA-MIS side to the CON side. Radiological
      results showed no differences in mean values between the two surgical groups,
      although the NA-MIS group contained fewer outliers than the CON group. In
      conclusion, NA-MIS TKA was associated with better clinical results up to 6 or 9
      months after surgery, giving more accurate leg alignment than CON TKA.

PMID- 17538793
TI  - Analysis of Common Deletion (CD) and a novel deletion of mitochondrial DNA
      induced by ionizing radiation.
AB  - PURPOSE: In order to identify supportive evidence of radiation exposure to cells,
      we analyzed the relationship between exposure to ionizing radiation and the
      induction of deletions in mitochondrial DNA (mtDNA). MATERIALS AND METHODS: Using
      human hepatoblastoma cell line, HepG2 and its derivatives, HepG2-A, -89 and -400,
      established after long term exposure to X-ray, mtDNA deletions were analyzed by
      polymerase chain reaction (PCR) and real-time PCR after cells were subjected to
      radiation and genotoxic treatments. RESULTS: Common Deletion (CD), the most
      extensively studied deletion of mtDNA, was induced within 24 h after exposure to
      5 Gray (Gy) of X-rays and was associated with replication of mtDNA. CD became
      undetectable several days after the exposure due to the death of cells containing
      mitochondria within which CD had been induced. Furthermore, we found a novel
      mtDNA deletion that consisted of a 4934 base-pair deletion (4934del) between
      nucleotide position 8435 and 13,368. A lower dose of ionizing radiation was
      required to induce the 4934del than for CD and this was independent of the
      quality of radiation used and was not induced by treatments with hydrogen
      peroxide (H(2)O(2)) and other genotoxic reagents including bleomycin. CONCLUSION:
      CD is induced by ionizing radiation, however, the amount of CD detected at a
      certain point in time after radiation exposure is dependent on the initial
      frequency of CD induced and the death rate of cells with mtDNA containing CD. The
      novel mtDNA deletion found in this study, therefore, will be used to determine
      whether cells were exposed to ionizing radiation.

PMID- 17538794
TI  - Hypoxia-regulated p53 and its effect on radiosensitivity in cancer cells.
AB  - PURPOSE: To determine the response of tumor suppressor p53 to hypoxia in
      different tumor cell lines and the involvement of p53 activity regulation in the
      effect of hypoxia on tumor cell sensitivity to radiation and hyperthermia.
      MATERIALS AND METHODS: Three tumor cell lines with functional p53 were treated
      with chronic or cyclic hypoxia followed by radiation or hyperthermia to
      investigate p53 activity and cell survival. Flow cytometry was used to
      investigate the effect of hypoxia-induced cell cycle arrest on radiosensitivity
      in KHT-C (mouse fibrosarcoma) cells. Transient transfection was performed to
      determine the role of altered p53 activity in KHT-C and SCC VII (mouse squamous
      cell carcinoma) radiosensitivity. RESULTS: Aerobic radiosensitivity was decreased
      in KHT-C and SCC VII cells after in vitro chronic or cyclic hypoxia pretreatment,
      but in HT1080 cells, it was slightly increased after chronic hypoxia, and was
      unchanged after acute hypoxia pretreatment. Decreased radiosensitivity in hypoxia
      pretreated KHT-C and SCC VII cells was unlikely due to hypoxia-induced cell cycle
      arrest, but rather seemed to be associated with increased expression of Mdm2
      (mouse double minute-2) and decreased p53. Furthermore, hypoxia pretreatment
      inhibited the activation of p53 by radiation. Similar results were observed in
      hyperthermia treated KHT-C cells. Finally, decreased radiosensitivity was
      observed in both KHT-C and SCC VII cells transiently transfected with Mdm2 or
      anti-sense p53 cDNA. CONCLUSION: We demonstrated that hypoxia may decrease tumor
      cell radiosensitivity through the suppression of p53 activity in some tumor cell
      lines. These results suggested the response of p53 to hypoxia can be cell type
      specific and contribute to radiosensitivity of hypoxic cells.

PMID- 17538795
TI  - Modified oxygen mask to induce target levels of hyperoxia and hypercarbia during
      radiotherapy: a more effective alternative to carbogen.
AB  - PURPOSE: Carbogen has long been under investigation as an adjuvant to
      radiotherapy of tumors. A major factor confounding its evaluation is its
      inconsistency in raising blood partial pressure of CO(2) (pCO(2)). We
      investigated whether a new partial rebreathing method would provide better
      control of pCO(2) than carbogen. METHODS AND MATERIALS: We compared the efficacy
      of each method in 10 healthy volunteers. Volunteers breathed 1.5, 3 and 5%
      carbogen in 5-min stages via the usual non-rebreathing circuit. All the
      volunteers then breathed 100% O(2) through a commercial sequential gas delivery
      (SGD) circuit modified by attaching a reservoir to its exhalation port.
      Hypercarbia was induced by step reductions in oxygen flow to the SGD circuit. We
      monitored minute ventilation and end-tidal pCO(2) (ETpCO(2)) as a surrogate for
      its arterial value. RESULTS: Inhalation of 1.5 and 3% carbogen did not increase
      ETpCO(2) from baseline (40 +/- 1.5 mmHg); 5% carbogen increased ETpCO(2) to 45 +/
      1.6 mmHg (p < 0.001). With the SGD circuit, reducing O(2) flow to 4.3 +/- 0.7
      l/min increased ETpCO(2) in all subjects from 41 +/- 2.0 mmHg (baseline) to 46 +/
      2.1 mmHg (p < 0.001). Voluntary hyperventilation reduced ETpCO(2) with 5%
      carbogen but not with SGD (p = 0.379). CONCLUSIONS: We confirm previous
      observations that carbogen inhalation does not result in a predictable rise in
      ETpCO(2) and suggest that a precise and stable target ETpCO(2) can instead be
      induced by simply controlling O(2) flow into a modified SGD circuit. We hoped
      that the reliable control of pCO(2) will enable studies that address first, the
      efficacy of raising ETpCO(2) on specific tumor blood flow, and eventually, its
      benefit as an adjuvant to radiotherapy.

PMID- 17538796
TI  - The two inducible responses, SOS and heat-shock, in Escherichia coli act
      synergistically during Weigle reactivation of the bacteriophage phiX174.
AB  - PURPOSE: The objective of this study was to investigate how Escherichia coli
      cells responded at the level of DNA repair, when the cells were subjected to UV
      (ultraviolet) radiation and heat-stress to induce a DNA repair system (SOS) and
      heat-shock response, respectively. MATERIALS AND METHODS: The experiments were
      performed to study the Weigle reactivation of the bacteriophage phiX174 in its
      host E. coli C/1 cells. Two distinct techniques, top layer agar plating and
      Western blotting, were employed to measure the plaque count of viable phages and
      to demonstrate the heat-shock response respectively. RESULTS: Repair of UV
      inactivated bacteriophages in UV-irradiated E. coli cells is known as Weigle
      reactivation. In the case of the single-stranded DNA containing bacteriophage
      phiX174, Weigle reactivation occurs only through the inducible SOS repair
      response. Here we report that when UV-irradiated E. coli cells were transferred
      to higher temperature, the consequent heat-shock enhanced the reactivation of UV
      inactivated phiX174 over normal Weigle reactivation; the enhancement being
      maximum when the cells were shifted from 30 - 47 degrees C and incubated there
      for 30 min. The extent of increase of reactivation was less, when the cells were
      first subjected to heat-shock and then irradiated by UV. Besides heat, ethanol (5
      - 10% volume/volume [v/v]), an established heat-shock inducer, also caused
      enhancement of phage reactivation and the maximum enhancement occurred at 8% v/v
      ethanol. CONCLUSION: We suggest that the SOS and heat-shock responses in E. coli
      act synergistically in the reactivation of UV-damaged bacteriophage phiX174.

PMID- 17538797
TI  - Canadian Cytogenetic Emergency network (CEN) for biological dosimetry following
      radiological/nuclear accidents.
AB  - PURPOSE: To test the ability of the cytogenetic emergency network (CEN) of
      laboratories, currently under development across Canada, to provide rapid
      biological dosimetry using the dicentric assay for triage assessment, that could
      be implemented in the event of a large-scale radiation/nuclear emergency.
      MATERIALS AND METHODS: A workshop was held in May 2004 in Toronto, Canada, to
      introduce the concept of CEN and recruit clinical cytogenetic laboratories at
      hospitals across the country. Slides were prepared for dicentric assay analysis
      following in vitro irradiation of blood to a range of gamma-ray doses. A minimum
      of 50 metaphases per slide were analyzed by 41 people at 22 different
      laboratories to estimate the exposure level. RESULTS: Dose estimates were
      calculated based on a dose response curve generated at Health Canada. There were
      a total of 104 dose estimates and 96 (92.3%) of them fell within the expected
      range using triage scoring criteria. Half of the laboratories analyzed 50
      metaphases in </= 1 hour and the time to score them was proportional to dose. The
      capacity and scoring expertise of the various participating laboratories were
      found to be generally acceptable. CONCLUSIONS: The dose estimates generated
      through triage scoring by this network were acceptable for emergency biological
      dosimetry. When this network is fully operational, it will be the first of its
      kind in Canada able to respond to radiological/nuclear emergencies by providing
      triage quality biological dosimetry for a large number of samples. This network
      represents an alternate expansion of existing international emergency biological
      dosimetry cytogenetic networks.

PMID- 17538798
TI  - Thresholds and transitions for activation of cellular radioprotective mechanisms 
      correlations between HRS/IRR and the 'inverse' dose-rate effect.
AB  - PURPOSE: In biophysical modeling for several instances of radiation-induced
      radioprotection, i.e., adaptive response (AR), hyper-radiosensitivity and induced
      radioresistance (HRS/IRR), and the inverse dose-rate effect (IDRE), empirical
      fits are premised for the thresholds and transitions of the radioprotection. We
      provide realistic model formulations for the observed behaviors, which we apply
      to both HRS/IRR and IDRE. MATERIALS AND METHODS: We use homeostatic balance
      equations, including cell biophysical endogenic adjustments (originating from
      within the cell), providing a radiation-induced 'trigger' or continuous
      thresholds and transitions. RESULTS: A 'trigger' threshold requires an
      instantaneous, step function. Current HRS/IRR transition model does not provide
      'triggered' threshold but continuous progression from high sensitivity to reduced
      radiosensitivity, although the investigators premise 'trigger' behavior. IDRE
      data suggest 'triggered' thresholds at discrete dose rates. It appears that
      HRS/IRR and IDRE at low dose and dose rate intentionally provide protection
      against potentially carcinogenic mutations. CONCLUSIONS: The homeostatic
      formulation shows, when applied to the IRR using a dose and dose rate dependent
      Linear-Quadratic model (LQ2), that the IRR protection is 'triggered' at a
      discrete low dose and induced by a transitory increase in the damage repair rate
      constant in the LQ2 model of the single event, linear response, radiation damage.
      Since both IDRE and IRR have 'triggered' thresholds and as a result of increased
      endogenic damage recognition, increased mobilization of repair resources,
      activation of cell cycle arrest and/or increased repair rate, we premise that
      both may be from the same endogenic radioprotection biochemical mechanisms.

PMID- 17538799
TI  - Environmental Mutagen Society symposium on 'Risks of low dose, low dose rate
      exposures of ionizing radiation to humans'.
AB  - The Symposium, held in Vancouver, Canada, on 17 - 21 September 2006, was
      organized by the Environmental Mutagen Society, and it was their 37th Annual
      Meeting. Sessions were chaired by Drs W. F. Morgan and J. L. Schwartz, and papers
      were presented by Drs R.C. von Borstel, D. J. Brenner, J. L. Redpath, B. E.
      Erickson and A.L. Brooks.

PMID- 17538800
TI  - Why don't patients get better? The three 'nons'.

PMID- 17538801
TI  - Folic acid in general medicine and dermatology.
AB  - Folic acid is a vitamin B essential for the integrity and function of DNA.
      Relative deficiency of folic acid may occur in conditions such as pregnancy and
      hyperproliferative or chronic inflammatory disorders. Folic acid supplementation
      has been proven to be beneficial in the prevention of neural tube defects and in
      limiting methotrexate side effects, and may reduce the risk of colorectal cancer.
      Folate is a critical vitamin in determining plasma homocysteine levels, which in
      turn is a major risk factor for cardiovascular diseases. The results of large
      clinical trials with dietary supplementation of folic acid, vitamin B12 and
      vitamin B6 have shown that this homocysteine-lowering therapy is effective in the
      secondary prevention of non-fatal strokes, but had no effect in the prevention of
      fatal cardiovascular diseases. Hyperhomocysteinemia has also been reported in age
      related neurological conditions with cognitive impairment (e.g. dementia), and
      psychiatric disorders such as depression. Elevated homocysteine levels are
      frequent in patients with chronic immune-mediated disorders including rheumatoid
      arthritis, systemic lupus erythematosus, chronic plaque psoriasis and psoriatic
      arthritis, which have in common a tendency to an accelerated atherosclerosis
      leading to increased deaths from cardiovascular events. Folic acid
      supplementation appears as a reasonable therapeutic option in patients affected
      by chronic inflammatory skin diseases, such as moderate to severe psoriasis; in
      particular, those with concomitant hyperhomocysteinemia, low plasma folate and
      additional cardiovascular risk factors.

PMID- 17538802
TI  - Pimecrolimus, yet another intriguing topical immunomodulator.
AB  - Pimecrolimus, yet another intriguing local immunomodulator, has been approved for
      use in atopic dermatitis in individuals of more then 2 years of age. However, its
      indications are now being extended to include a variety of inflammatory
      dermatoses, which are identified in the current article with a proviso that their
      use should be considered only as an alternative when conventional modalities have
      failed.

PMID- 17538803
TI  - Tacrolimus ointment is more effective than pimecrolimus cream in adult patients
      with moderate to very severe atopic dermatitis.
AB  - OBJECTIVE: To compare the efficacy and safety of tacrolimus ointment 0.1% and
      pimecrolimus cream 1% in adult patients with moderate to very severe atopic
      dermatitis (AD). METHODS: A total of 281 patients (141 treated with tacrolimus
      and 140 treated with pimecrolimus) were randomized to a multicenter, investigator
      blinded, 6-week study. RESULTS: Tacrolimus-treated patients had significantly
      greater improvements in the Eczema Area Severity Index score compared with
      pimecrolimus-treated patients (mean percent reduction from baseline to study end:
      57% vs 39%, respectively; p=0.0002). Treatment success was also significantly
      greater among the tacrolimus-treated patients compared with pimecrolimus-treated
      patients (40% vs 22% at study end; p=0.001), as was the improvement in percentage
      of total body surface area affected (a reduction of 49% vs 34% at study end;
      p=0.01). Both treatment groups had similar improvements in patient assessment of
      itch. There were no significant differences in the incidences of adverse events,
      including application-site burning and application-site pruritus, the two most
      commonly reported adverse events. Significantly more pimecrolimus-treated
      patients than tacrolimus-treated patients withdrew from the study due to lack of
      efficacy (10 vs 1, p=0.005). CONCLUSION: Tacrolimus ointment is more effective
      than pimecrolimus cream in adults with moderate to very severe AD. Both agents
      have a similar safety profile.

PMID- 17538804
TI  - Beneficial use of Cetaphil moisturizing cream as part of a daily skin care
      regimen for individuals with rosacea.
AB  - INTRODUCTION: Rosacea is a common and chronic disorder characterized by flushing,
      erythema, papules, pustules, and telangiectasia on the central part of the face.
      Because the facial skin of individuals with rosacea is particularly sensitive,
      irritants can trigger a worsening of the signs and symptoms of the disease. This
      enhanced sensitivity is thought to be linked to a deficient stratum corneum
      barrier function. MATERIALS AND METHODS: In the present study, 20 individuals
      receiving twice-daily applications of metronidazole 0.75% gel for at least 15
      days applied a gentle non-irritating moisturizing cream (Cetaphil Moisturizing
      Cream) twice daily for 15 days on one half of the face; the other side remained
      treated with metronidazole only and served as the control. RESULTS: Clinical
      assessments, confirmed by biophysical measurements (electrical capacitance,
      transepidermal water loss (TEWL), and lactic acid stinging test), provided
      evidence that the moisturizer contributed to the restoration of the skin barrier:
      skin dryness, roughness and desquamation were much improved and skin sensitivity
      was significantly reduced. Skin properties and skin discomfort were also greatly
      enhanced and the patients were very satisfied with the product. CONCLUSIONS: It
      can thus be concluded that in the management of rosacea, basic skin care
      regimens, including daily use of a therapeutic moisturizer, offer optimal
      benefits.

PMID- 17538805
TI  - Short-duration topical treatment of tinea pedis using terbinafine emulsion gel:
      results of a dose-ranging clinical trial.
AB  - BACKGROUND: In the treatment of tinea pedis, current terbinafine formulations are
      applied once or twice daily for 7 days. A terbinafine emulsion gel formulation
      has been developed to provide a 5-day treatment course for tinea pedis.
      OBJECTIVE: To determine the lowest effective concentration of terbinafine (1% or
      3%) emulsion gel applied once daily for 5 days for the treatment of tinea pedis.
      METHODS: This double-blind, placebo-controlled study evaluated the efficacy of 1%
      and 3% terbinafine gel for 5 days in 84 outpatients with tinea pedis. The primary
      efficacy endpoint was the percentage of patients with effective treatment
      (negative microscopy and culture with only mild erythema/desquamation/pruritus
      [total score<or=2]) at study endpoint (last post-baseline observation up to and
      including week 6). RESULTS: Efficacy rates with terbinafine 1% and 3% emulsion
      gel were significantly higher than with placebo (86% and 68% vs 11%,
      respectively; p<0.001). Similarly, mycological cure rates were significantly
      greater with terbinafine 1% and 3% gel (97% and 89%, respectively) than with
      placebo (22%; p<0.001). CONCLUSIONS: Terbinafine 1% emulsion gel used once daily
      for 5 days was the lowest effective concentration, and was significantly superior
      to placebo. Both concentrations were effective and safe, providing convenient,
      short-duration treatment of tinea pedis.

PMID- 17538806
TI  - Epidermal nevi treated by carbon dioxide laser vaporization: a series of 25
      patients.
AB  - BACKGROUND: Epidermal nevi are benign proliferations of epidermis. Numerous
      treatment modalities have been tried, but no ideal treatment is yet available.
      OBJECTIVE: To report our experience with CO(2) laser vaporization in the
      treatment of verrucous epidermal nevi, and to identify which factors could have
      influence in long-term results. METHODS: A total of 25 patients were treated with
      the CO(2) laser in the superpulsed mode, focalized at 2 W/cm(2). The patients
      were between 3 and 41 years old (mean: 17 years). A total of 44% of lesions were
      <20 cm(2), 40% measured between 20 and 100 cm(2) and 16% were >100 cm(2). The
      follow-up was 4-79 months (mean: 28 months). In 76% of patients, multiple
      treatment sessions were required. RESULTS: Good results were achieved in 92% of
      patients with soft, flattened nevi and in only 33% patients with keratotic nevi.
      In addition, 87% of the latter had moderate results and 12.5% had poor results.
      CONCLUSION: We conclude that the CO(2) laser in superpulsed mode is an effective
      and safe treatment for verrucous epidermal nevi and provides fewer recurrences
      than other laser therapies. We also believe that the most determining factor for
      the cosmetic result is thickness of the nevus.

PMID- 17538807
TI  - Nail psoriasis improvement in a patient treated with fumaric acid esters.
AB  - Nail psoriasis is common in adult psoriatic patients and it causes serious
      psychological and physical distress. Topical treatments such as corticosteroids,
      calcipotriol, retinoids, and 5-fluorouracil have limited efficacy and are not
      without side effects. Relative effective systemic treatments are ciclosporin,
      methotrexate and acitretin, all of which have a serious toxicity potential.
      Biologics in the treatment of nail psoriasis have been the subject of recent
      research, but their cost-effectiveness is questionable. We present a case of
      psoriatic nail disease which improved greatly on treatment with fumaric acid
      esters (FAE).

PMID- 17538808
TI  - Treatment of refractory pemphigus vulgaris with anti-CD20 monoclonal antibody
      (rituximab): five cases.
AB  - BACKGROUND: Pemphigus vulgaris is an autoimmune disease characterized by blisters
      and widespread erosions, involving skin and mucous membranes, caused by
      autoantibodies to desmoglein 1 and 3. This pathology is associated with increased
      morbidity and mortality if untreated. The treatment of pemphigus vulgaris
      requires multiple immunosuppressive agents, but often it is particularly
      resistant. OBJECTIVE: To evaluate the efficacy and safety of rituximab therapy in
      refractory pemphigus vulgaris. METHODS: Five patients diagnosed as having
      pemphigus vulgaris were treated with anti-CD20 monoclonal antibody (rituximab).
      Each patient was treated with rituximab intravenously at a dosage of 375 mg per
      square metre of body surface area once weekly for 4 weeks. RESULTS: All the
      patients presented clinical resolution. No adverse effects were observed. It is
      important to observe the clinical evolution in the future, but our experience is
      still limited to a short lifetime and follow-up. CONCLUSION: In our experience
      rituximab has been an effective and safe treatment for refractory pemphigus
      vulgaris.

PMID- 17538809
TI  - Anetodermic mastocytosis: response to PUVA therapy.
AB  - Mastocytosis is a group of disorders characterized by the accumulation of mast
      cells in different tissues and organs. The skin is the most frequently involved
      organ (90% of cases) where mastocytosis may show a heterogenic clinical
      expression. Anetodermic lesions are an unusual clinical presentation of
      mastocytosis. We report a case of anetodermic mastocytosis in a 26-year-old man,
      with sparse lesions and a benign course. PUVA therapy obtained excellent results
      in this case. Darier's sign should be investigated in patients with anetodermic
      lesions of unclear origin in order to exclude cutaneous mastocytosis.

PMID- 17538810
TI  - Genital porokeratosis: treatment with diclofenac topical gel.
AB  - Genital porokeratosis (PK) is a rare and probably underestimated subset of PK
      that mostly affects middle-aged men. As in other clinical variants of PK,
      management can be difficult. Surgery and CO(2) laser vaporization may be
      efficient on individual lesions but topical treatment can be considered when the
      elements are more scattered and/or more numerous. We report the case of a 68-year
      old man with a disseminated PK following a 20-year history of lesions restricted
      to the genitalia for whom 3% diclofenac gel succeeded in stabilizing their
      evolution and achieving symptomatic relief. In conclusion, topical diclofenac
      could be worth considering in the management of genital PK with numerous lesions.

PMID- 17538811
TI  - Treatment of genital Paget's skin disease with topical imiquimod: severe adverse
      events.

PMID- 17538812
TI  - Analysis of portable impactor performance for enumeration of viable bioaerosols.
AB  - Portable impactors are increasingly being used to estimate concentration of
      bioaerosols in residential and occupational environments; however, little data
      are available about their performance. This study investigated the overall
      performances of the SMA MicroPortable, BioCulture, Microflow, Microbiological Air
      Sampler (MAS-100), Millipore Air Tester, SAS Super 180, and RCS High Flow
      portable microbial samplers when collecting bacteria and fungi both indoors and
      outdoors. The performance of these samplers was compared with that of the
      BioStage impactor. The Button Aerosol Sampler equipped with gelatin filter was
      also included in the study. Results showed that the sampling environment can have
      a statistically significant effect on sampler performance, most likely due to the
      differences in airborne microorganism composition and/or their size distribution.
      Data analysis using analysis of variance showed that the relative performance of
      all samplers (except the RCS High Flow and MAS-100) was statistically different
      (lower) compared with the BioStage. The MAS-100 also had statistically higher
      performance compared with other portable samplers except the RCS High Flow. The
      Millipore Air Tester and the SMA had the lowest performances. The relative
      performance of the impactors was described using a multiple linear regression
      model (R(2) = 0.83); the effects of the samplers' cutoff sizes and jet-to-plate
      distances as predictor variables were statistically significant. The data
      presented in this study will help field professionals in selecting bioaerosol
      samplers. The developed empirical formula describing the overall performance of
      bioaerosol impactors can assist in sampler design.

PMID- 17538813
TI  - The influence of social and cultural factors on infertility and new reproductive
      technologies.

PMID- 17538814
TI  - The value of children in African countries: insights from studies on infertility.
AB  - A number of studies have explored motives for parenthood in the Western
      industrialized world. These studies have documented that children are mostly
      desired for reasons relating to happiness and personal well-being. To date,
      limited data pertaining to parenthood motives in African countries exist. Insight
      into the value of children can, however, be derived from studies on infertility,
      as the negative repercussions of involuntary childlessness reflect the value of
      children to parents and the community. According to these studies children secure
      conjugal ties, offer social security, assist with labour, confer social status,
      secure rights of property and inheritance, provide continuity through re
      incarnation and maintaining the family lineage, and satisfy emotional needs.
      Parenthood therefore appears to have more and, arguably, deeper roots in African
      communities when compared to industrialized countries.

PMID- 17538815
TI  - The socio-cultural and biological meaning of parenthood.
AB  - Parenting a child is one of the most universal, common and fundamental
      assumptions the majority of men and women make from an early age about their
      future. This common and historic assumption was challenged in modernized Western
      societies in the 1960s with the opportunities for 'mass control' of reproduction
      and then again supported in the 1980s with the advance of 'mass enhancement' of
      reproduction. This study qualitatively assessed the meaning of parenthood of post
      modern British individuals of different ages, gender, cultural backgrounds and
      parity. The results of the Interpretative Phenomenological Analyses revealed a
      number of common ideologies about parenthood, and a number of specific age,
      gender, parity and cultural differences in how individuals interpret and
      experience parenthood. These individual differences play a significant part in
      the quality of life of people gaining or losing the opportunity to parent, as has
      been discussed 'around the globe' by Frank van Balen and his team, and must be
      considered in counselling people faced with decisions which challenge their
      personal and universal assumptions to parent a genetically related child.

PMID- 17538816
TI  - Emotional distress and infertility: Turkish migrant couples compared to Dutch
      couples and couples in Western Turkey.
AB  - The present study investigates cultural differences in the effects of infertility
      on emotional distress. The study compares emotional distress among infertile
      people in three samples: Turkish migrants (n = 58), Turkish people living in
      Western Turkey (n = 46), and Dutch people (n = 199). Participants answered
      structured questionnaires on self-image, blame-guilt, sexual problems,
      depression, anxiety, and anger-hostility. Separate analyses were conducted for
      men and women. In general, the levels of emotional distress were higher for
      infertile Turkish migrant women and infertile Turkish women than they were for
      infertile Dutch women. Turkish migrant women reported more self-image problems
      and fewer feelings of blame-guilt than did Turkish women. Among men, Turkish
      migrant men showed the highest overall levels of emotional distress, and Dutch
      men showed the lowest. Our results indicate that the experience of infertility
      among Turkish migrants is more similar to those of Turkish people than it is to
      that of Dutch people, especially among women. The importance of having children
      in the different cultures may offer a possible explanation for these findings.

PMID- 17538817
TI  - Becoming a mother by non-anonymous egg donation: secrecy and the relationship
      between egg recipient, egg donor and egg donation child.
AB  - The object of the study was to investigate secrecy in non-anonymous egg donation,
      to explore some characteristics of this kind of egg donation arrangement and the
      relationship of the recipient with her non-genetic child. Forty-four egg
      recipients and 62 IVF patients with a child conceived through egg donation and/or
      IVF were recruited. A semi-structured questionnaire was sent to all the
      participants. Chi-square and T-tests were used to examine the differences between
      the groups. There were no significant differences on the following aspects. The
      same high proportion of egg donation mothers (77%) and IVF mothers (87%) had the
      intention of telling their child about the conception but most women thought
      disclosure at a later time preferable. Two thirds of the recipients and IVF
      mothers said the way of conception had no influence on the relationship with
      their child. The two groups differed however in their argumentation about secrecy
      and named different feelings. Egg donation mothers expressed more denial and
      showed more defensive reactions, anxieties and uncertainty. It is suggested that
      recognition of a certain difference between a natural conception and egg donation
      could be helpful in early disclosure and could help to diminish anxieties in egg
      donation mothers.

PMID- 17538818
TI  - Patterns of suffering and social interactions in infertile men: 12 months after
      unsuccessful treatment.
AB  - Research shows that men diagnosed with male factor infertility experience more
      suffering than men with infertility due to other causes, and that it is socially
      unfavourable to be diagnosed with male factor infertility resulting in secrecy
      surrounding diagnosis, sometimes to the point that women take the blame for the
      couples' infertility. We investigated mental and physical health, support, and
      psychological and social stress in men (N = 256) prior to and after 12 months of
      unsuccessful treatment according to their diagnosis: unexplained, female factor,
      male factor, or mixed. Results suggest that men do not differ by diagnosis on any
      of the variables tested. When treatment was not successful, all men showed
      increased suffering in the form of decreased mental health, increased physical
      stress reactions, decreased social support, and increased negative social stress
      over time. These findings indicate that involuntary childlessness is difficult
      for all men, and is not dependent on with whom the cause lies. There was also a
      high level of agreement between couples and medical records on the cause of the
      couples' fertility arguing against the idea that women take the blame for male
      factor infertility.

PMID- 17538819
TI  - Consequences of IVF among women: 10 years post-treatment.
AB  - Between 2.1% and 4.2% of all children born in Scandinavian countries are
      conceived with the help of assisted reproductive technology. The present study is
      one of the first to have followed up infertile women over a long period. Data on
      outcomes, satisfaction and the perceived consequences of IVF treatment were
      collected by means of a questionnaire among a random sample of women (response
      rate 42%; N = 66) who had undergone IVF at a tertiary referral university
      hospital in Norway. It was found that 10 years post-treatment, the majority of
      the women had children, whether through adoption, spontaneous pregnancy or IVF. A
      remarkable number of the women neither had told nor intended to tell their
      children that they had been conceived through IVF. Although most of the women
      said that they regard the treatment period as a painful one, they also said that
      it was now in the past and no longer affected their lives in a devastating way:
      they had found a way to cope with this difficult period in their life.

PMID- 17538820
TI  - Child adjustment and parenting in planned lesbian families with known and as-yet
      unknown donors.
AB  - The present study examined child adjustment, experience of parenthood, and child
      rearing between two types of planned lesbian families (i.e., two-mother families
      in which the child had been born to the lesbian relationship), viz. those with a
      known donor (n = 42) and those with an as-yet unknown donor (n = 58) (both with
      children between 4 - 8 years old). Data were collected by means of parental
      reports and standardized instruments were used in the questionnaires (e.g., Child
      Behaviour Checklist; CBCL). No differences were found on internalizing,
      externalizing and total problem behaviour scales of the CBCL between children
      with a known and a currently unknown donor, nor were differences found on
      parental stress and child rearing. However, social problems were more frequently
      reported for the children with known donors, and boys with a known donor showed
      more attention problems. Furthermore, annoying questions from people in their
      social environment as well as gossip and feelings of being excluded, were more
      frequently reported by mothers with a (currently) unknown donor.

PMID- 17538821
TI  - Medical schools--do they add value?

PMID- 17538822
TI  - From calling to a scheduled vocation: Swedish male and female students'
      reflections on being a doctor.
AB  - BACKGROUND: All over the world an increasing number of women are entering medical
      schools. Soon women will constitute half of the physician workforce in
      Scandinavia. However, specialty segregation persists. Reports have shown
      different motives among male and female doctors to be, but the impact of gender,
      i.e. how ongoing social constructions of femininity and masculinity influence the
      development of professionalism, is not fully described. AIM: The purpose of this
      study was to explore views and visions among second-year students at a Swedish
      Medical School, and to identify challenges for education and workforce planning.
      METHODS: After receiving research ethics board approval, all students
      participating in the course 'Professional development', including a task to write
      a free-text essay on the theme 'to be a doctor', were invited to share their
      essays for analysis. Of 138 (40% men) students in 2002, 104 (39% men) accepted.
      The texts were analysed according to grounded theory. RESULTS: Students held
      'doctorship' to be an outstanding profession of commitment, authority and duty.
      Fears were exposed, especially among women, regarding how to fit demands of self
      sacrifices and balancing a private life. Belonging to a new generation, they
      conceived gender equity as self-evident. Actual working conditions were met with
      disapproval, as did an all-embracing calling. A scheduled vocation was hoped for.
      They relied on the mass of women to implement change. Women's 'other' values,
      alluding to family orientation, were expected to alter working conditions and
      also give men more leisure time. Despite equity conviction, segregating gender
      patterns in students' representations, interactions with tutors and future
      prospects were disclosed. CONCLUSIONS: Students' arguments raise challenges for
      medical educators and planners regarding professional values, medical
      socialization and specialty recruitment. The new generation requires a renewed
      Hippocratic Oath, gender-aware role models and practice sites. Swedish students'
      arguments are compared with current international literature.

PMID- 17538823
TI  - AMEE Guide No. 27: Effective educational and clinical supervision.
AB  - BACKGROUND: This guide reviews what is known about educational and clinical
      supervision practice through a literature review and a questionnaire survey. It
      identifies the need for a definition and for explicit guidelines on supervision.
      There is strong evidence that, whilst supervision is considered to be both
      important and effective, practice is highly variable. In some cases, there is
      inadequate coverage and frequency of supervision activities. There is particular
      concern about lack of supervision for emergency and 'out of hours work', failure
      to formally address under-performance, lack of commitment to supervision and
      finding sufficient time for supervision. There is a need for an effective system
      to address both poor performance and inadequate supervision. Supervision is
      defined, in this guide as: 'The provision of guidance and feedback on matters of
      personal, professional and educational development in the context of a trainee's
      experience of providing safe and appropriate patient care.' A framework for
      effective supervision is provided: (1) Effective supervision should be offered in
      context; supervisors must be aware of local postgraduate training bodies' and
      institutions' requirements; (2) Direct supervision with trainee and supervisor
      working together and observing each other positively affects patient outcome and
      trainee development; (3) Constructive feedback is essential and should be
      frequent; (4) Supervision should be structured and there should be regular
      timetabled meetings. The content of supervision meetings should be agreed and
      learning objectives determined at the beginning of the supervisory relationship.
      Supervision contracts can be useful tools and should include detail regarding
      frequency, duration and content of supervision; appraisal and assessment;
      learning objectives and any specific requirements; (5) Supervision should include
      clinical management; teaching and research; management and administration;
      pastoral care; interpersonal skills; personal development; reflection; (6) The
      quality of the supervisory relationship strongly affects the effectiveness of
      supervision. Specific aspects include continuity over time in the supervisory
      relationship, that the supervisees control the product of supervision (there is
      some suggestion that supervision is only effective when this is the case) and
      that there is some reflection by both participants. The relationship is partly
      influenced by the supervisor's commitment to teaching as well as both the
      attitudes and commitment of supervisor and trainee; (7) Training for supervisors
      needs to include some of the following: understanding teaching; assessment;
      counselling skills; appraisal; feedback; careers advice; interpersonal skills.
      Supervisors (and trainees) need to understand that: (1) helpful supervisory
      behaviours include giving direct guidance on clinical work, linking theory and
      practice, engaging in joint problem-solving and offering feedback, reassurance
      and providing role models; (2) ineffective supervisory behaviours include
      rigidity; low empathy; failure to offer support; failure to follow supervisees'
      concerns; not teaching; being indirect and intolerant and emphasizing evaluation
      and negative aspects; (3) in addition to supervisory skills, effective
      supervisors need to have good interpersonal skills, good teaching skills and be
      clinically competent and knowledgeable.

PMID- 17538824
TI  - Online collaborative learning for healthcare continuing professional development:
      a cross-case analysis of three case studies.
AB  - There has been increasing interest in the use of computers to facilitate
      collaborative learning between healthcare professionals for continuing
      professional development but many schemes appear to be unsuccessful. The aim of
      the study was to identify, from a cross-case analysis of three case studies, the
      main factors that facilitate and inhibit online collaborative learning for
      healthcare continuing professional development. The intervention was an
      asynchronous, structured and moderated discussion board. Data were collected by
      semi-structured telephone interviews on a purposive sample from each case study,
      documentary analysis of all self-reported comments made in the discussion boards,
      log of technical problems and evaluation of discussion board activity. Three key
      factors were identified: the need for implementation based on the requirements of
      users, the acceptance of this approach by the user and the development of a
      supportive organization within which the healthcare professionals work. This
      study has highlighted the overall low level of activity and this would appear to
      be because implementation has not been based on an understanding of the
      healthcare context.

PMID- 17538825
TI  - Different outcomes of active and reflective students in problem-based learning.
AB  - BACKGROUND: In the recent past, many medical schools have adopted the problem
      based learning (PBL) method in their curriculum. AIM: The key in this type of
      learning is the small group, which encourages students to perform and, thus, to
      learn effectively. This means the students must be grouped in such a way for the
      small group to facilitate the achievement of a better learning outcome. METHODS:
      Using Felder's Learning Inventory, three groups of students were formed: active,
      reflective and a control with no particular propensity. RESULTS: Some interesting
      results were found. Active learners did not have the highest score in any of the
      tested areas. Instead, the reflective group of learners had the best outcome in
      participation, and the control group showed the best teamwork in a PBL setting.
      CONCLUSION: Overall, we have found that grouping students according to their
      varying learning styles can be very useful for specific and various learning
      outcomes.

PMID- 17538826
TI  - An overview of the world's medical schools.
AB  - BACKGROUND: In the past several years, there has been a rapid expansion in the
      number of medical schools. Presently, there are over 1,900 operating medical
      schools in the world, located on six of the seven continents. Regrettably, other
      than for select countries and regions, relatively little is known about the
      characteristics or the quality of these institutions. DESCRIPTION: The
      International Medical Education Directory (IMED) provides an accurate and up-to
      date resource of information about medical schools. Based on current listings in
      IMED, the geographical distribution of medical schools does not mirror the
      regional population. The Caribbean, with a total population of less than 40
      million, has 54 operating medical schools. In contrast, of the 57 African
      nations, 16 did not have a single medical school. CONCLUSIONS: Given the
      physician's role in the healthcare team, the challenges presented by migration of
      healthcare workers, and questions concerning the adequacy of existing
      institutions to meet healthcare needs, developing and maintaining accurate and
      detailed information on the world's medical schools and their graduates is
      paramount.

PMID- 17538827
TI  - Physician assistants: education, practice and global interest.
AB  - BACKGROUND: In the United States, the physician assistant (PA) model has proven
      to be a cost-effective way to train quality primary care providers with a high
      degree of acceptance of the PA role by patients and other healthcare providers.
      AIM: Discuss PA model as it pertains to other countries. METHODS: Review of
      relevant literature related to physician assistant education, practice and global
      interest. RESULTS: Several countries including the United Kingdom, Scotland,
      Canada, The Netherlands, Taiwan, South Africa and Ghana are exploring or re
      exploring the concept of the physician assistant as a way to quickly and
      efficiently train and employ autonomous and flexible health workers to address
      their nation's healthcare needs. CONCLUSIONS: Physician assistant education is
      efficient and flexible and the PA model can be easily adapted to the specific
      health system needs of other nations. In addition, many PA programs have
      affiliation agreements with institutions outside of the United States to host PA
      students for clinical rotations and there is an ever-growing interest by students
      in international rotations. The Physician Assistant Education Association along
      with the American Academy of Physician Assistants is actively involved with
      sharing information about the PA profession with other countries.

PMID- 17538828
TI  - Maximizing the value of feedback for individual facilitator and faculty
      development in a problem-based learning curriculum.
AB  - BACKGROUND: Recruiting and retaining facilitators in problem-based learning
      requires considerable staff development. Providing meaningful feedback to
      individual facilitators should contribute to improved management of the tutorial
      group. AIM: To ascertain the value ascribed by facilitators to feedback they
      received (based on student input) regarding their performance in the small group
      tutorial in a new problem-based learning curriculum. METHODS: Thirty-seven
      facilitators from a purposive sample, selected for their facilitation experience
      during the 2001-2003 period, completed a comprehensive survey regarding their
      experiences. The aspect currently being reported deals with the perceived
      usefulness of the feedback they received from students and from Faculty following
      the evaluation of their participation in the small group tutorial. Data are
      reported for medically qualified and non-medically qualified facilitators.
      RESULTS: Both clinical (50%) but more notably the non-clinical (70%) facilitators
      found the feedback (individual facilitator and general report) useful.
      Facilitators generally preferred the qualitative comments provided by students in
      the open-ended section of the evaluation to the Likert scale items. Student
      comments were valued for the specific direction they offered facilitators to
      reflect and improve on their management of the small group. For this feedback to
      be more useful, however, facilitators believed that it needed to be completed by
      more students who took time to critically engage with the criteria and reflect
      more honestly on their experiences. In addition, facilitators requested for
      feedback reports to be made available sooner such that they could improve their
      facilitation skills for the next group of students. CONCLUSIONS: Both qualitative
      and quantitative feedback are important for facilitator development and training.
      While quantitative feedback is important for summative purposes (e.g. quality
      assurance and promotion), individual student comments provide more formative
      feedback, allowing facilitators to reflect on and improve their management of the
      small group. In order for the feedback to be valid, the majority of students had
      to participate. Facilitators should receive feedback in time to allow them to
      modify their activities for the new group.

PMID- 17538829
TI  - A qualitative study of medical school choice in the UK.
AB  - BACKGROUND: Examining the factors that make a medical school attractive (or
      otherwise) to potential students is particularly important but there is little
      empirical evidence that explores this issue. METHODS: Semi-structured interviews
      were undertaken with 24 prospective medical students at six schools and colleges
      in England. The interviews aimed to elicit detailed information on the why and
      how of medical school choice, in students' application and acceptance decisions.
      RESULTS: Three categories of medical school attributes stood out as positive
      determinants of choice: academic factors (with reputation considered the most
      important), location factors (specifically preferences for particular cities) and
      intangibles (gut feelings and personal contacts and recommendations). Most of
      students' decision-making activity was undertaken during the admissions stage of
      the application process. CONCLUSIONS: The results are important in explaining why
      the students in the sample did not rate the new medical schools highly and also
      suggest that few of the important attributes can be manipulated by the schools
      themselves.

PMID- 17538830
TI  - Revival of the case method: a way to retain student-centred learning in a post
      PBL era.
AB  - BACKGROUND: In current renewal of medical education, problem-based learning (PBL)
      is the predominant approach. PBL is afflicted with limitations, which cause
      uncertainness about its future. A profoundly different approach is the case
      method, developed a century ago and today attracting much less interest in
      developmental work than PBL. AIM: To compare the characteristics of PBL and the
      case method and ask the question of whether the case method may serve as an
      alternative approach to student-centred learning. METHOD: The comparison was
      literature-based. RESULTS: PBL implicates fostering of self-directed learning and
      its prospects deal with depth and retention of knowledge and clinical reasoning
      skills. Problems are used to define learning goals and to stimulate students'
      interest in various aspects of an item, rather than just for problem-solving. In
      the small-group tutorials of a PBL curriculum, the teacher is assigned to
      facilitate the process of self-directed learning and needs not necessarily be a
      subject-matter expert. In spite of its exciting philosophy and an increased input
      of students' and teachers' time, the superiority of PBL as a mode of learning has
      not been convincingly demonstrated, either in terms of acquisition of knowledge
      or in clinical performance. Moreover, dysfunction is a well-recognized
      phenomenon. In some PBL tutorials, indifference towards the group discussion is
      encountered, including individual quietness or dominant behaviour and incomplete
      attendance. To cope with dysfunctional problems, efforts are recommended aiming
      to increase PBL tutors' and students' understanding of the group process. As
      opposed to PBL, the case method relies strongly on teacher-directed learning.
      Students are placed in a dilemma or a problem to be solved. After preparatory
      work, they meet for a discussion, lead by a subject-matter expert, who preferably
      has experienced the case in reality. As a chairperson, the teacher is supposed to
      stimulate the discussion and detect gaps and misunderstandings. Due to its
      teacher-dependent approach to learning, the case method is less susceptible to
      group dysfunction. The case method is also less resource consuming, primarily
      because it can be practised in groups several times larger than those of PBL.
      CONCLUSION: A revival of the case method seems warranted as an alternative means
      of interactive learning, which is simpler, easier to realize and less time
      consuming with regard to both institutions and students.

PMID- 17538831
TI  - Patient-centred learning--back to the future.
AB  - BACKGROUND: Historically, medical students learned the art and science of
      medicine from the patients they encountered. While students were highly motivated
      to learn through this approach, the serendipitous nature of real practice and the
      variability in the skills of their teachers proved to be liabilities for
      learning. This apprenticeship-style education was replaced by a more formal
      didactic curriculum during the twentieth century. DESCRIPTION: The power of
      computer technology enables medical educators to recapture the authenticity of
      patient-centred learning (PCL) through the creation of a virtual practice
      populated by a panel of virtual patients. In contrast to traditional problem
      based learning cases, PCL virtual patients return for multiple visits with their
      student-doctors, demonstrating how diseases change over time, interact with other
      diseases and risk factors, and are influenced by psychosocial factors.
      CONCLUSIONS: New approaches to pedagogy embodied in patient-centred learning
      allow the curriculum to be organized around the patients, both real and
      simulated.

PMID- 17538832
TI  - Active learning in medical education: strategies for beginning implementation.
AB  - Medical educators often deliver complex material in a format that does not allow
      the positive learning engagement recommended by cognitive researchers and
      theorists. Intentional engagement and active learning pedagogies change the
      nature of learning, while simultaneously improving knowledge gain and recall
      abilities. Students find the work more interesting and thereby put more effort
      into it. Historical perspective reveals that medical faculty need to make changes
      in their teaching methodologies. However, transforming pedagogical practice is
      difficult, as medical faculty have not had much exposure to pedagogical theory or
      training. While simple steps can be taken to alter basic lecture formatting,
      these steps may be unfamiliar to medical faculty. Seven methods for adapting
      parts of lectures are described. Practice with such methods may engender
      exploration of epistemological and cognitive aspects of deeper understanding.

PMID- 17538833
TI  - Performance-based self-esteem and burnout in a cross-sectional study of medical
      students.
AB  - OBJECTIVES: To examine levels of burnout among medical students and test the
      hypothesis that high performance-based self-esteem is associated with burnout.
      Further to study associations between burnout and self-rated health. DESIGN:
      Cross-sectional survey, of medical students at 1st, 3rd and 6th year of medical
      school, N = 342, 59.1% women. MEASURES: Burnout was monitored by the Oldenburg
      Burnout Inventory (OLBI), comprising Exhaustion and Disengagement dimensions.
      Performance-based self-esteem (PBSE) was assessed by the PBSE-scale (PBSS) and
      self-rated health by SRH-5. RESULTS: The response rate was 90.4%. Females were
      more exhausted than males and sixth year students were most disengaged. High
      performance-based self-esteem was present in 41.7% of the respondents and poor
      health in 10.7%. Performance-based self-esteem had significant and moderate
      correlations with both burnout dimensions. Logistic regression showed a positive
      association between poor health and Exhaustion. CONCLUSIONS: Exhaustion among
      medical students was significantly associated with poor health, and deserves
      attention from teachers. Performance-based self-esteem was higher than in other
      populations and associated with both burnout dimensions, but not with poor
      health. Further research on study environment and burnout is needed, and the
      reasons for female students' higher exhaustion levels should be further
      investigated.

PMID- 17538834
TI  - Composition of the panel of reference for concordance tests: do teaching
      functions have an impact on examinees' ranks and absolute scores?
AB  - BACKGROUND: Concordance tests are designed to assess the component of uncertainty
      of clinical reasoning. Scoring is based on a comparison of examinees' answers
      with those of a panel of reference, including their variability. This allows
      construction of tests that are close to real clinical life, with all its
      complexity and ambiguity. AIM: This study was carried out to determine the effect
      of teaching functions of members composing the reference panels on students'
      scores and ranking. METHODS: A group of 80 residents in family medicine from a
      French University (Bobigny) completed a 72-item concordance test. The answers of
      two panels, each made up of 29 family physicians (teaching function versus non
      teaching function), were used to generate the correction keys. RESULTS:
      Correlation between the sets of data obtained with the two panels is high (ICC =
      0.98). Concordance scores obtained from the teaching-function panel are higher
      than scores obtained from the non-teaching-function panel (72.0 versus 76.3; p <
      0.001). Ranking provided by the two panels was very similar. CONCLUSIONS: This
      legitimizes the use of non-teaching physicians on panels. Panel composition
      influenced absolute score values: Residents showed more concordance with their
      academic trainers than with community-based physicians.

PMID- 17538835
TI  - Addressing the hidden curriculum: understanding educator professionalism.
AB  - Several authors agree that student observations of behaviors are a far greater
      influence than prescriptions for behavior offered in the classroom. While these
      authors stress the importance of modeling of professional relationships with
      patients and colleagues, at times they have fallen short of acknowledging the
      importance of the values inherent in the role of the professional educator. This
      includes relationships and concomitant behaviors that stem from the
      responsibilities of being an educator based on expectations of institutional and
      societal culture. While medical professionals share standards of medical practice
      in exercising medical knowledge, few have obtained formal training in the
      knowledge, skills and attitudes requisite for teaching excellence. Attention
      needs to be paid to the professionalization of medical educators as teachers, a
      professionalization process that parallels and often intersects the values and
      behaviors of medical practice but remains a distinct and important body of
      knowledge and skills unto itself. Enhancing educator professionalism is a
      critical issue in educational reform, increasing accountability for meeting
      student needs. Assumptions regarding educator professionalism are subject to
      personal and cultural interpretation, warranting additional dialogue and research
      as we work to expand definitions and guidelines that assess and reward educator
      performance.

PMID- 17538836
TI  - Teaching medical students in their last leg of the undergraduate journey.
AB  - BACKGROUND: This short biographical piece provides a brief description of the
      experience of a medical teacher at the University of the West Indies in Jamaica.
      It traces his initial response to being chosen as a teacher and shows movement
      from self-doubt to assertive thinking about the role of the teacher. The
      development of the teacher, though buttressed by a formal training intervention,
      is couched within a sensitive understanding of the whole student.

PMID- 17538837
TI  - Educating undergraduate medical students about patient safety: priority areas for
      curriculum development.
AB  - Learning about patient safety is an important aspect of undergraduate medical
      curricula but there are no clear priority areas. A recent consensus of
      international medical educators identified several priority areas and these
      recommendations include approaches to increase knowledge of patient safety,
      including the causes and frequency, to develop willingness to take
      responsibility, to develop self awareness of the situations when patient safety
      is compromised, to develop communication skills, especially inter-personal, and
      to develop team working skills.

PMID- 17538838
TI  - Ethics and evaluating educational programmes.

PMID- 17538844
TI  - A pilot study showing an association between platelet hyperactivity and the
      severity of peripheral arterial disease.
AB  - Peripheral arterial disease (PAD) is a chronic fibroproliferative inflammatory
      condition associated with progressive vascular stenosis. We set out to determine
      the relationship between spontaneous stirring-induced platelet aggregation in
      whole blood and the severity of lower-limb PAD, represented by the ankle-brachial
      pressure index (ABPI). ABPI was determined pre- and post-exercise in 31 subjects
      (20 men and 11 women) with established PAD. Platelets counts were determined in
      EDTA blood (total count) and in citrated whole blood after stirring in the
      absence of added ADP (spontaneous aggregation) and in the presence of added ADP
      (ADP-induced) for 3 min at 37 degrees C. Aggregation was calculated as a
      percentage of the total platelet count. Spontaneous platelet aggregation showed
      an inverse correlation with pre-exercise ABPI (r = -0.32; P < 0.05) and ADP
      induced aggregation correlated inversely with post-exercise ABPI (r = -0.34; P <
      0.05). These results indicate that platelet hyperactivity is associated with
      increasing severity of PAD. Increased platelet aggregation may result in
      thromboembolic events in the affected limb.

PMID- 17538845
TI  - Diagnostic performance of the platelet function analyzer (PFA-100) for the
      detection of disorders of primary haemostasis in patients with a bleeding history
      a systematic review and meta-analysis.
AB  - The Platelet Function Analyzer (PFA-100) is increasingly being used in the workup
      of patients with a bleeding diathesis. A profound knowledge of the possible
      diagnostic performance of this test is essential in order to make sound clinical
      decisions based on its results. It was the aim of this study to systematically
      review the published literature and provide valid estimates of the diagnostic
      performance of the PFA-100 for detecting disorders of primary haemostasis in
      newly presenting patients with a bleeding diathesis. A comprehensive literature
      search was performed for studies published between January 1994 and February
      2006. Studies were eligible for the systematic review if they provided data
      supposed to be applicable to the determination of the diagnostic performance of
      the PFA-100. Furthermore, they were included in a meta-analysis if study
      reporting allowed calculation of sensitivity and specificity and if study quality
      ensured minimized biases of these estimates for the described clinical setting.
      Pooled weighted sensitivity, specificity and diagnostic odds ratio were
      calculated applying random effects modelling and constructing summary operator
      characteristic curves. This was done separately for the available test
      modifications using either collagen/epinephrine (PFA-EPI) or collagen/adenosine
      diphosphate (PFA-ADP) for platelet activation. Thirty-six articles were included
      in the systematic review. Six studies met our eligibility criteria for a meta
      analysis. The major reason for exclusion from the meta-analysis was a case
      control design. A total of 1486 and 1259 patients were included in the meta
      analysis of the diagnostic performance of the PFA-EPI and PFA-ADP, respectively.
      Pooled weighted sensitivity and specificity of the PFA-EPI/PFA-ADP in detecting a
      disorder of primary haemostasis were: 82.5/66.9% (95%-confidence interval (95%
      CI): 76.0-88.9%/57.9-75.9%), and 88.7/85.5% (95%-CI: 84.3-93.1%/82.0-89.1%).
      83/75% of patients with a positive PFA-EPI/PFA-ADP result do have a disorder of
      primary haemostasis whereas 88/79% with a negative PFA-EPI/PFA-ADP result do not.
      The PFA-EPI appeared to have a higher sensitivity and better predictive values
      than the PFA-ADP in detecting disorders of primary haemostasis, although a
      rigorous gold standard definition for a disorder of primary haemostasis,
      particularly for platelet disorders, was not applied in most studies. The
      majority of the studies lacked important requirements for quality and reporting,
      precluding a more precise and definitive characterization of the clinical utility
      of the PFA-100. This emphasizes the need for an evidence-based critical appraisal
      of diagnostic studies in haemostasis research in order to promote the conducting
      of studies that produce clinically relevant results.

PMID- 17538846
TI  - Platelet reactivity among Asian Indians and Caucasians.
AB  - Asian Indians are reported to have higher mortality and morbidity from coronary
      artery disease (CAD) than other ethnic groups. This variation in events cannot be
      explained only by differences in conventional risk factors. Platelet activation
      is an important factor in the pathogenesis of CAD, however, there are limited
      data concerning platelet reactivity in Asian Indians. Therefore, we aimed to
      examine platelet reactivity in healthy Asian Indians vs. Caucasians. Thirty-five
      healthy, nonsmoking Asian Indians (mean age 30.1 +/- 3.6 years, 31.4% women) were
      matched for age and sex with 35 healthy, nonsmoking Caucasians (mean age 30.8 +/-
      5 years, 31.4% women). Platelet reactivity was evaluated by measuring platelet
      aggregation, platelet leukocyte aggregates (PLA) formation in response to a 6-mer
      thrombin receptor agonist peptide (TRAP) at a final concentration of 40 microM
      and flow cytometry determined P-selectin expression induced by ADP, TRAP and
      arachidonic acid (AA). In addition, P-Selectin glycoprotein ligand-1 (PSGL-1)
      density on leukocytes was measured. There were no differences in platelet
      aggregation, basal PLA or PSGL-1 density on leukocytes between the two groups. AA
      stimulated P-selectin expression was significantly higher in Asian Indians than
      in Caucasians (6.1 +/- 0.51 vs. 4.2 +/- 0.41 MFI, P < 0.02). After stimulation
      with TRAP, platelets from Asian Indians had increased PLA formation compared with
      Caucasians (41.6 +/- 2.9% vs. 31.4 +/- 2.7%, P < 0.02). AA induced P-selectin
      expression and TRAP stimulated PLA formation is increased in Asian Indians
      compared with Caucasians. These differences indicate an increase in measures of
      platelet reactivity among Asian Indians and may help elucidate the reported
      disparity in cardiovascular disease rates between the two ethnic groups.

PMID- 17538847
TI  - Molecular cloning and sequence analysis of alboaggregin B.
AB  - Green pit viper (Trimeresurus albolabris) venom contains a variety of C-type
      lectin-like proteins (CLPs) causing platelet aggregation and consumptive
      thrombocytopenia in biting victims. Alboaggregin B (AL-B), a heterodimeric
      glycoprotein (Gp) Ib-binding protein, was purified from the venom, but there is
      no reported cDNA sequence and the platelet agglutination mechanism is poorly
      understood. The full-length AL-B beta clone was obtained from T. albolabris venom
      gland cDNA library. AL-B alpha was, later, derived using 3'-RACE based on the
      conserved sequence. In this study, purified AL-B dimer agglutinated human
      platelets with the EC(50) of 180 nM and was completely inhibited by anti GpIb
      antibody. MALDI ToF mass spectroscopy found no glycosylation. The peptide mass
      fingerprints were matched with deduced amino acid sequences of cloned genes. AL-B
      alpha and beta contained 156 and 146 amino acid, respectively, including 23
      residue signal peptides. AL-B beta showed the conserved hydrophilic patches,
      putative sites for GpIb binding. Furthermore, there was another conserved motif
      (SRTY) exclusively in platelet-agglutinating AL-B, TSV-GPIb-BP and Mamushigin. We
      propose that these three CLPs may function as bivalent adhesive proteins linking
      two GpIb molecules on adjacent platelets.

PMID- 17538848
TI  - Platelet pathology in sex-linked GATA-1 dyserythropoietic macrothrombocytopenia I
      ultrastructure.
AB  - Various mutations in the X-linked transcription factor, GATA-1, may result in
      dyserythropoietic anemia, macrothrombocytopenia and/or erythropoietic porphyria.
      The present study has carried out detailed ultrastructural studies of abnormal
      platelet morphology in one, previously described family with a GATA-1 G208S
      mutation. The ultrastructural investigations revealed a large proportion of their
      circulating platelets were hypogranular macrothrombocytes, resembling cells from
      patients with the Gray Platelet Syndrome. However, most of their platelets
      contained some alpha granules and a small number contained as many as are present
      in normal platelets. GATA-1 platelets from family members also contained tubular
      inclusions formed from elements of the dense tubular system like those observed
      in the Medich Giant Platelets Disorder. The unique pathology of the GATA-1 family
      platelets found in this study involved features never observed previously in
      normal or abnormal platelets. Many of their cells contained unusual flat, tubular
      membrane sheets, often in parallel association and differing from all other
      membrane systems in normal platelets and megakaryocytes. In some
      macrothrombocytes the unusual membranes appeared to isolate areas of cytoplasm.
      The sequestered areas were platelets within platelets. On rare occasion there
      were two platelets within one platelet, or, even more rarely, a platelet within a
      platelet within a platelet. Another unique feature, probably related to platelets
      within platelets, was the frequent attachment of non-activated platelets to each
      other to form macrothrombocytes. GATA-1 platelets within platelets and attached
      to platelets, as well as giant platelets, suggest that proplatelet formation may
      be abnormal, or that GATA-1 platelets are unable to pinch off from megakaryocyte
      proplatelets in a normal manner.

PMID- 17538849
TI  - Mean platelet volume: association with adverse neonatal outcome.
AB  - The aim of the study was to investigate on a possible association between
      maternal mean platelet volume (MPV) and oxygen-metabolic changes in pregnancies
      affected by altered maternal-fetal Doppler velocimetry. We considered the altered
      maternal-fetal Doppler velocimetry group (n = 57) pregnant women admitted to our
      Institution for a pregnancy complication associated to the event Pre-eclampsia
      (PE) and intrauterine growth retardation (IUGR), with altered Doppler velocimetry
      in the umbilical artery ( UA) (high pulsatility index, absence or reverse end
      diastolic flow (ARED), blood flow cephalisation) and/or bilateral increased
      resistance in uterine arteries. Out of these cases, 25 pregnancies were
      complicated by PE and 32 pregnancies were complicated by IUGR. We included 145
      normotensive third trimester pregnant women as a normal maternal-fetal Doppler
      velocimetry control group. From all women, 20 ml of whole venous blood was
      obtained from the antecubital vein soon after Doppler velocimetry evaluation. MPV
      was significantly higher in women with abnormal Doppler velocimetry compared to
      those with normal Doppler velocimetry (8.0 fl [7.0-8.7] vs. 9.1 fl [8.0-10.6],
      <0.001. Values are median [interquartiles]). We performed a ROC curve in order to
      find an MPV cut-off able to predict an uneventful event in Doppler velocimetry
      compromised fetuses (neonatal O(2) support > 48 hrs or intubation and/or pH < 7.2
      at umbilical blood gas analysis (UBGA)). An MPV > or = 10 fl was significantly
      related to the former diagnostic endpoints compared to that of non-compromised
      fetuses (sensitivity: 45%, specificity: 89.7%, 95 CI: 18.8-66, p < 0.01). Our
      study suggests that pregnancies affected by Doppler velocimetry alterations, an
      MPV value > or = 10 fl may be associated with severe oxygen support and/or low UA
      ph at birth.

PMID- 17538852
TI  - Very old people's experience of occupational performance outside the home:
      possibilities and limitations.
AB  - To support occupations outside the home for older people with functional
      limitations it is important to understand how the person, environment, and
      occupations influence performance. Therefore the purpose of this study was to
      describe how very old people experience occupational performance outside the
      home. Twenty-one single-living, very old persons, above 80 years, were
      strategically selected and interviewed. A phenomenographic approach was used for
      this study and the interviews were analyzed using contextual analysis. The
      findings showed a variation in the experience of occupational performance
      described in three referential aspects: keeping on doing as before, drawing on
      available resources, and living in constrained circumstances. Referring to
      everyday occupations the participants described how they continued to do what
      they had done before, but decline in functional capacity made it more difficult
      to overcome environmental barriers. They also described how they sometimes could
      put functional limitations aside and use their utmost capacity to reach their
      goals. When they could not do that any more, they had to find possibilities for
      occupations close to home. In order to support very old people's occupational
      performance outside the home, outdoor mobility has to be facilitated, including
      the design of the physical environment as well as possibilities for social
      interaction.

PMID- 17538853
TI  - The influence of the environment on participation subsequent to rehabilitation as
      experienced by elderly people in Norway.
AB  - The aim of this study was to illuminate how the environment may influence
      participation among elderly people who have undergone community-based
      rehabilitation in Norway, after an acute illness or accident. Fourteen persons
      over 65 years of age were selected with the specific intention of gaining a
      variety of ages, both genders, and people living in different kinds of housing.
      Three focus groups were established and repeated interviews were held with each
      group. A constant comparative analysis was used to analyse the data. The main
      finding was that the participants experienced pressure from their environment to
      concentrate on performing the most necessary daily activities rather than on
      participation. Three main encounters with environments seemed to be important for
      this: encountering people and society, encountering private and formal
      assistance, and encountering occupation. The support that the participants
      received from family and friends was more important for their participation than
      having accessible physical environments. The findings suggest that occupational
      therapists must consider themselves to be part of a societal environment that can
      hinder participation.

PMID- 17538854
TI  - Occupational patterns of people with dementia in residential care: an
      ethnographic study.
AB  - This paper describes an ethnographic study that sought to gain knowledge of the
      occupational patterns of persons with dementia in a care home and how the
      residents perceived the group activities in which they participated. The
      residents' ages ranged from 82 to 92 years. They were seven women and one man.
      Both participant observation and interviews were used to collect data. Data
      analysis resulted in an ethnographic story organised around two key themes: (1)
      the occupational patterns of the residents, and (2) the residents' perceptions of
      the activities offered. In this story residents appeared passive, playing the
      role of guests in the care home. Residents were dependent on staff to engage in
      daily occupations. Interviews revealed that residents perceived participation in
      activities as important to their mental and physical health and an advantage of
      living in the care home.

PMID- 17538855
TI  - Women with rheumatoid arthritis: non-vocational activities and quality of life.
AB  - The aim of this study was to examine a possible relationship between partaking in
      non-vocational activities and health-related quality of life in women with
      rheumatoid arthritis (RA). Two questionnaires were completed by 45 women with RA
      aged from 25 to 80. The MOS Short-Form 36 (SF-36) measured the health-related
      quality of life and the Interest Checklist measured the amount of non-vocational
      activities performed. The present study revealed a significant decrease in non
      vocational activities by the participants during the last 10 years. Mental health
      status seemed to be of greater importance than physical function to perform non
      vocational activities in daily life. There were indications that a high number of
      activities performed correlated positively with scores on psychological well
      being, and that a low amount of activities performed correlated with the
      psychological distress scores.

PMID- 17538856
TI  - Participation in everyday occupations in a late phase of recovery after brain
      injury.
AB  - The aim of this study was to describe to what extent individuals of working age,
      in a late phase after an acquired brain injury, participate in everyday
      occupations related to home maintenance, work, and leisure. The aim was also to
      evaluate if participation in different occupations influences their life
      satisfaction. A sample of 157 people consecutively admitted to a rehabilitation
      clinic between June 1995 and December 2000 answered a mailed questionnaire. The
      subjects who were of working age had had a brain injury on average 6 years before
      this study. The perceived participation was reported using the Reintegration to
      Normal Living Index (RNL) and life satisfaction according to an expanded version
      of the LiSat 11. This study showed that in this late phase of recovery after
      brain injury the subjects still experienced many restrictions in participation in
      everyday occupations. The area with the lowest reported participation was work
      activity while most comfort with the situation was reported for self-care. The
      RNL subscales showed a significant connection with satisfaction with life as a
      whole. Furthermore an interaction was found between the two subscales "Daily
      living" and "Perception of self". This study showed restrictions in participation
      in the community even several years after brain injury, which underlines the need
      for rehabilitation services long after injury.

PMID- 17538857
TI  - Development and Rasch analysis of the Assessment of Computer-Related Skills.
AB  - The purpose of this study is to evaluate the internal scale validity, person
      response validity, and reliability of the newly developed Assessment of Computer
      Related Skills (ACRS). Data from 32 healthy adult participants who performed two
      to three computer tasks were analysed to determine how well the participants
      fitted the many-faceted Rasch (MFR) model of the ACRS, as well as how well the
      ACRS skill items and tasks (a) fitted the MFR model of the ACRS, (b) matched the
      expectations for hierarchical ordering of their difficulties, and (c)
      differentiated persons into different levels of ability. Results indicated that
      with three skill items removed, the remaining 34 skill items, 8 computer tasks,
      and 30 participants demonstrated goodness-of-fit to the MFR model of the ACRS.
      The skills and tasks appeared to have logical hierarchical ordering and
      differentiated participants into at least three levels of ability. The findings
      affirmed the internal scale validity, person response validity and reliability of
      the ACRS for assessing persons' computer abilities. Future studies using a larger
      sample that includes individuals with disabilities and with difficulties with
      computer use are needed to further evaluate the validity and reliability of the
      ACRS.

PMID- 17538859
TI  - [Experimental investigations on middle ear prostheses with an integrated micro
      joint].
AB  - BACKGROUND: Quasi static pressure changes as they occur in altitude changes or
      Valsalva's manoeuvre are causing great tympanic membrane displacements. These can
      produce a prosthesis dislocation from the stapes footplate, in case of using a
      TORP for reconstruction. Additionally, prostheses extrusions can occur in the
      chronically poor ventilated middle ear. Anatomical studies on the ostrich
      demonstrate that the flexible columella in the avian middle ear provides a good
      sound transmission and features an effective inner ear protection in pressure
      changes. MATERIAL AND METHODS: Focusing on this bionic attempt, we designed a new
      micro joint TORP by interposing a silicone ball joint in the prosthesis shaft.
      This prototype was used for frequency response measurements with the laser
      Doppler vibrometer in the ventilated middle ear and under conditions of increased
      pressure in the external auditory canal. RESULTS: Frequency response measurements
      showed comparable results to those using a conventional TORP. Investigations on
      pressure changes in the external auditory canal demonstrated a significant
      decrease in footplate excursion after reconstruction with the new micro-joint
      prosthesis then compared to a common TORP. CONCLUSIONS: The insertion of the new
      silicone bordered micro joint into a TORP shaft provides an effective method to
      decrease the potentially damaging stapes footplate excursions after complete
      ossicular reconstruction. Limited deflections of the prosthesis shaft reduce the
      occurring forces on the stapes footplate as they partly bore the quasi static
      pressure changes. Thus, the micro joint can reduce the risk of prostheses
      dislocation and annular ligament damage and is additionally providing a proper
      sound transmission through the reconstructed middle ear. Moreover, the bionic
      modification of a TORP reflects the remaining possibilities for further
      improvements in prosthetic reconstruction.

PMID- 17538860
TI  - [Are there alternative therapeutical options other than CPAP in the treatment of
      the obstructive sleep apnea syndrome].
AB  - Many patients with the obstructive sleep apnea syndrome (OSAS) look for
      alternative conservative or surgical therapies to avoid to be treated with
      continuous positive airway pressure. In view of the high prevalence and the
      relevant impairment of the patients lots of methods are offered which promise
      definitive cure or relevant improvement of OSAS. The working group "Apnea" in the
      German Society of Sleep Medicine and Research established a task force to
      evaluate the scientific literature on non-CPAP therapies in the treatment of OSAS
      according to the standards of evidence-based medicine. This paper summarizes the
      results of the task force. The data were unsatisfactorily for most of the
      methods. Sufficient data were available for intraoral appliances (IOA) and the
      maxillomandibular osteotomy (MMO). IOA's can reduce mild to moderate respiratory
      disturbances, MMO are efficient in the short and long term but are performed only
      in special situations such as craniofacial dysmorphias. Weight reduction and body
      positioning cannot be recommended as a single treatment of OSAS. Most surgical
      procedures still lack sufficient data according to the criteria of evidence based
      medicine. Resections of muscular tissue within the soft palate have to be
      strictly avoided. But even success following gentle soft palate procedures is
      difficult to predict and often decreases after years. Results in other anatomical
      regions seem to be more stable over time. Today combined surgeries in the sense
      of multi-level surgery concepts are of increasing interest in the secondary
      treatment after failure of nasal ventilation therapy although more data from
      prospective controlled studies are needed. There is no evidence for any other
      treatment options.

PMID- 17538861
TI  - ["The silent sister". A clinical thermometer in world literature].

PMID- 17538862
TI  - Phylogenetic background of Orange lily (Lilium bulbiferum s.l.) cultivars from a
      genetically isolated environment.
AB  - Domesticated Orange lily ( LILIUM BULBIFERUM s.l.) cultivars do not typically
      produce seeds, and Orange lily is not native to Finland. Therefore, back crossing
      of the cultivars with wild species has not been possible. Genetic variability and
      genuineness of eight Finnish traditionally-grown Orange lily cultivars was
      studied. RAPD patterns were compared between the cultivars and genuine Orange
      lily ( LILIUM BULBIFERUM L.), and a related Dauricum group. The results showed
      partition of tested genotypes into four groups, L. CANADENSE as the outgroup. The
      cultivars were divided into two subgroups where the trait to form bulbils was
      characteristic to subgroup I. The cultivated strains differed from each other as
      much as from the seedling strains, but were genetically closer to genuine Orange
      lily than the Dauricum group. This indicates that the cultivars are genuine forms
      of Orange lily species. The special morphological features of the cultivars have
      likely been formed during centuries-long genetic isolation from natural
      populations.

PMID- 17538863
TI  - Morphology and anatomy of shoot, root, and propagation systems in Hoffmannseggia
      glauca.
AB  - Hoffmannseggia glauca is a perennial weed that has tubers and root-borne buds.
      Some authors only consider root tubers without mentioning root-borne buds, while
      others consider that more anatomic studies become necessary to determine the
      origin of these structures and to interpret their behaviour. The objectives are:
      to study the growth form of the plant in order to analyze the ontogeny of its
      propagation organs, and to study its shoot and root anatomical characters that
      affect water conductivity. Hoffmannseggia glauca was collected in Argentina.
      Development of its shoot and root systems was observed. Shoots and roots were
      processed to obtain histological slides. Macerations were prepared to study
      vessel members. Primary and lateral roots originate buds that develop shoots at
      the end of the first year. In winter, aerial parts die and only latent buds at
      soil surface level and subterranean organs remain. In the following spring, they
      develop innovation shoots. Roots show localized swellings (tuberous roots), due
      to a pronounced increase of ray thickness and parenchymatous proliferation in the
      root center. Root vessel members are wider than those of aerial and subterranean
      shoots. Early development of an extensive root system, presence of root borne
      buds, anatomic and physiological specialization of innovation shoots, capability
      of parenchymatous rays to originate buds and tuberous roots, and high water
      transport efficiency in subterranean organs lead Hoffmannseggia glauca to display
      higher colonization potential than other species.

PMID- 17538864
TI  - Relationships among three pathways for resource acquisition and their
      contribution to plant performance in the emergent aquatic Plant Lythrum salicaria
      (L.).
AB  - Three pathways for resource acquisition exist in the emergent aquatic plant,
      Lythrum salicaria (L.); a subterranean root system, a free-floating adventitious
      root system, and arbuscular mycorrhiza (AM) fungal hyphae colonizing subterranean
      roots. This study examined the relationship(s) among these pathways and their
      contribution to plant performance. If the free-floating adventitious root system
      and/or AM fungi contribute to plant growth in wetland habitats, we predicted that
      their absence would result in a significant reduction in plant performance.
      Furthermore, if a reduction in resource uptake, effected by an absence of free
      floating adventitious roots and/or AM fungi, is compensated for by increased
      allocation to remaining pathway(s) for resource uptake, we predicted altered
      patterns of resource allocation among shoots and the remaining pathway(s) for
      resource uptake. Contrary to our predications, plants experiencing adventitious
      root removal and/or grown in the absence of AM fungi generally had greater
      biomass and total shoot height than controls. Similarly, while levels of AM
      colonization and subterranean root biomass displayed a treatment effect, the
      observed responses did not correspond with our predictions. This was also true
      for shoot : subterranean root dry weight ratios. Our results indicate that there
      is interaction among the 3 pathways for resource acquisition in L. salicaria and
      an effect on plant performance. The adaptive significance of these
      characteristics is unclear, highlighting the potential difficulties in
      extrapolating from terrestrial to aquatic plant species and among aquatic plant
      species with potentially different life history strategies.

PMID- 17538865
TI  - Timing of sexual reproduction and reproductive success in the high-mountain plant
      Saxifraga bryoides L.
AB  - SAXIFRAGA BRYOIDES L. is one of the plant species reaching the upper limits of
      distribution for flowering plants in the European Alps. Because of its abundance
      in the subnival and nival zones, we expected S. BRYOIDES to reproduce efficiently
      in the highly stochastic climate at higher altitudes. Investigations were carried
      out at two subnival sites (2650 m and 2880 m a.s.l.) in the Austrian Alps. We
      studied flowering phenology, dynamics of seed development, and reproductive
      success in the climatically different years from 2001 - 2004. For a nival plant
      species, S. BRYOIDES showed a particularly long prefloration period (6 - 9
      weeks). From onset of anthesis until seed maturity took an individual flower
      another 6 - 7 weeks and all individuals at a site 9 - 10 weeks. The length of the
      prefloration period and seed histogenesis was temperature-dependent, whereas seed
      maturation seemed to be endogenously controlled. Only in the exceptionally long
      and warm growing season of 2003 did all fruits mature at a site. In the other
      years, the onset of winter conditions halted development in many fruits before
      maturity. The seed/ovule ratio of mature fruits was around 0.7 in all years. The
      relative reproductive success (RRS) ranged from zero to 0.7, depending on the
      site and year. In conclusion, S. BRYOIDES needs an unexpectedly long time to
      undergo reproductive development. Though fruit maturation is uncertain, the high
      S/O ratio of single intact fruits results in at least a small seed crop in most
      years. This seems to be sufficient to assure the spread and maintenance of S.
      BRYOIDES at higher altitudes. As a seed-risk strategist (Molau,1993), S. BRYOIDES
      would clearly benefit from a prolonged growing season, which might occur more
      often if climate warming continues.

PMID- 17538866
TI  - Stomatal uptake and stomatal deposition of ozone in isoprene and monoterpene
      emitting plants.
AB  - Volatile isoprenoids were reported to protect plants against ozone. To understand
      whether this could be the result of a direct scavenging of ozone by these
      molecules, the stomatal and non-stomatal uptake of ozone was estimated in plants
      emitting isoprene or monoterpenes. Ozone uptake by holm oak (Quercus ilex, a
      monoterpene emitter) and black poplar (Populus nigra, an isoprene emitter) was
      studied in whole plant enclosures (continuously stirred tank reactors, CSTR). The
      ozone uptake by plants was estimated measuring ozone concentration at the inlet
      and outlet of the reactors, after correcting for the uptake of the enclosure
      materials. Destruction of ozone at the cuticle or at the plant stems was found to
      be negligible compared to the ozone uptake through the stomata. For both plant
      species, a relationship between stomatal conductance and ozone uptake was found.
      For the poplar, the measured ozone losses were explained by the uptake of ozone
      through the stomata only, and ozone destruction by gas phase reactions with
      isoprene was negligible. For the oak, gas phase reactions of ozone with the
      monoterpenes emitted by the plants contributed significantly to ozone
      destruction. This was confirmed by two different experiments showing a) that in
      cases of high stomatal conductance but under low CO(2) concentration, a reduction
      of monoterpene emission was still associated with reduced O(3) uptake; and b)
      that ozone losses due to the gas phase reactions only can be measured when using
      the exhaust from a plant chamber to determine the gas phase reactivity in an
      empty reaction chamber. Monoterpenes can therefore relevantly scavenge ozone at
      leaf level contributing to protection against ozone.

PMID- 17538867
TI  - Cut-induced VOC emissions from agricultural grasslands.
AB  - The introduction of proton transfer reaction mass spectrometry (PTR-MS) for fast
      response measurements of volatile organic compounds (VOC) has enabled the use of
      eddy covariance methods to investigate VOC fluxes on the ecosystem scale. In this
      study PTR-MS flux measurements of VOC were performed over agricultural grassland
      during and after a cut event. Selected masses detected by the PTR-MS showed
      fluxes of methanol, acetaldehyde, and acetone. They were highest directly after
      cutting and during the hay drying phase. Simultaneously, significant fluxes of
      protonated ion masses 73, 81, and 83 were observed. Due to the limited
      identification of compounds with the PTR-MS technique, GC-MS and GC-FID-PTR-MS
      techniques were additionally applied. In this way, ion mass 73 could be
      identified as 2-butanone, mass 81 mainly as (Z)-3-hexenal, and mass 83 mainly as
      the sum of (Z)-3-hexenol and hexenyl acetates. Hexenal, hexenols, and the hexenyl
      acetates are mostly related to plant wounding during cutting. It was found that
      legume plants and forbs emit a higher number of different VOC species than
      graminoids.

PMID- 17538868
TI  - The role of alkamides as an active principle of echinacea.
AB  - Alkamides are the major lipophilic constituents of ECHINACEA preparations, which
      are widely used in some European countries and in North America for common colds.
      In earlier investigations they have been shown to possess stimulatory effects on
      phagocytosis. Recent experiments have demonstrated that alkamides are detectable
      in human blood in relevant concentrations after oral administration of Echinacea
      preparations. Alkamides show structural similarity with anandamide, an endogenous
      ligand of cannabinoid receptors. Consequently, it was found that alkamides bind
      significantly to CB (2) receptors, which is now considered as a possible
      molecular mode of action of Echinacea alkamides as immunomodulatory agents. It
      was also demonstrated recently in several studies that alkamide-containing
      Echinacea preparations trigger effects on the pro-inflammatory cytokines. They
      were therefore suggested as a new class of cannabinomimetics. However, the
      therapeutic relevance of these findings is still not clear as clinical studies on
      the common cold show contradictory results. Among the many pharmacological
      properties reported, investigations concerning herb-drug interactions have been
      neglected for a long time. Latest research concludes that prolonged use of
      Echinacea poses a minimal risk for co-medications metabolized by the P450
      enzymes.

PMID- 17538869
TI  - Red American ginseng: ginsenoside constituents and antiproliferative activities
      of heat-processed Panax quinquefolius roots.
AB  - Red Asian ginseng ( Panax ginseng C. A. Meyer, Araliaceae) is used in many
      Oriental countries. In this study, the saponin constituents and anticancer
      activities of steamed American ginseng ( Panax quinquefolius L.) roots were
      evaluated. The contents of 12 ginsenosides in the roots were determined using
      high performance liquid chromatography (HPLC). After the steaming treatment (100 
      120 degrees C for 1 h and 120 degrees C for 0.5 - 4 h), the quantity of 7
      ginsenosides decreased and that of 5 others increased. The content of ginsenoside
      Rg3, a previously recognized anticancer compound, increased significantly when
      the root was steamed at 120 degrees C for 0.5 - 3 h. The antiproliferative
      effects of unsteamed and steamed (120 degrees C for 1 h and 2 h) American ginseng
      root extracts were assayed by the modified trichrome stain (MTS) method using
      three cancer cell lines (SW-480, HT-29, NSCLC). Heat-processing increased the
      antiproliferative effect of American ginseng significantly, and the activity of
      the extract from roots steamed for 2 h was greater than that of roots steamed for
      1 h. Chemical constituents and antiproliferative activities of white and red
      Asian ginseng have also been evaluated. Five representative ginsenosides, Rb1,
      Rd, Re, Rg2 and Rg3, were studied. Ginsenoside Rg3 had the most potent effect.
      The antiproliferative activities of red American ginseng are augmented when
      ginsenoside Rg3 is increased.

PMID- 17538870
TI  - Immunosuppressive lignans isolated from Saururus chinensis.
AB  - Bioactivity-guided fractionation of Saururus chinensis (Saururaceae) using a
      lymphoproliferation assay led us to isolate 5 lignans (compounds 1 - 5).
      Compounds 1 - 5 were identified as sauchinone, (-)-saucerneol, saucerneol C,
      manassantin A, and manassantin B, respectively, by spectroscopic analyses. The
      immunosuppressive activities of the active compounds were evaluated using
      lymphoproliferation, mixed leukocyte response, and Th1/Th2 cytokine assays. The
      relative potency was in the order: manassantin A, B > (-)-saucerneol > saucerneol
      C > sauchinone.

PMID- 17538871
TI  - Anti-inflammatory activity of phenylpropanoids and phytoquinoids from Illicium
      species in RBL-2H3 cells.
AB  - Two phenylpropanoids, 1-allyl-3,5-dimethoxy-4-(3-methyl-but-2-enyloxy)benzene (
      4) and 4-allyl-2,6-dimethoxy-3-(3-methyl-2-butenyl)phenol ( 6), and two
      phytoquinoids, 4 R-(-)-illicinone-A ( 7) and 2 S,4 R-(-)-illicinone-B ( 8),
      isolated from plants of the ILLICIUM species significantly inhibited histamine
      release from rat basophilic leukemia (RBL-2H3) cells stimulated with A23187.
      Furthermore, these compounds caused a decline in TNF-alpha levels in culture
      supernatants of RBL-2H3 cells following treatment with A23187. The results
      indicate that these compounds might be useful as anti-inflammatory agents against
      mast cell-mediated inflammatory diseases.

PMID- 17538872
TI  - Inhibition of chitin synthase 2 and antifungal activity of lignans from the stem
      bark of Lindera erythrocarpa.
AB  - Potent chitin synthase 2 inhibitors, methyllinderone (1), linderone (2) and
      kanakugiol (3) were isolated from the stem bark of L. erythrocarpa Makino
      (Lauraceae). These compounds inhibited chitin synthase 2 with IC(50) values of
      23.3, 21.4 and 23.8 microg/mL, respectively. Methyllinderone (1) and linderone
      (2) exhibited no inhibitory activities for chitin synthases 1 and 3 from S.
      cerevisiae, and chitin synthase 1 from Candida albicans up to the concentration
      of 280 microg/mL, while kanakugiol (3) exhibited very weak activity against
      chitin synthase 1 of C. albicans with an IC(50) of 160 microg/mL. All of the
      compounds showed moderate to weak antifungal activities against various
      pathogenic fungi (MIC: 8 - >128 microg/mL) including Cryptococcus neoformans,
      Aspergillus fumigatus, and Colletotrichum lagenarium. The results indicate that
      these compounds are specific inhibitors of chitin synthase 2 and can potentially
      serve as antifungal agents.

PMID- 17538873
TI  - Cognition-enhancing and neuroprotective effects of hederacolchiside-E from
      Pulsatilla koreana.
AB  - The root extract of Pulsatilla koreana (Ranunculaceae) has been found to have
      prominent abilities to reverse scopolamine-induced cognitive impairment in rats,
      and to increase the viability of human neuroblastoma SK-N-SH cells incubated with
      amyloid-beta peptide (1 - 42) [A beta (1 - 42)]. In vivo and in vitro activity
      guided fractionation studies using solvent-partitioning and subsequent
      chromatographic separations led to the isolation of hederacolchiside-E, an
      oleanolic glycoside, as an active ingredient. Administration of hederacolchiside
      E (30 and 60 mg/kg body weight, P. O.) increased the step-through latency time in
      the passive avoidance test as efficiently as tacrine (30 mg/kg, P. O.). The
      neuroprotective effect of hederacolchiside-E on SK-N-SH cells against the
      toxicity of A beta (1 - 42) was comparable to that of catechin. These data
      suggest that hederacolchiside-E might be a good therapeutic candidate for the
      treatment of Alzheimer's disease.

PMID- 17538874
TI  - Breast-feeding and HIV-1 transmission: how risky for how long?

PMID- 17538875
TI  - What causes prolonged fatigue after infectious mononucleosis: and does it tell us
      anything about chronic fatigue syndrome?

PMID- 17538876
TI  - The language used by Helicobacter pylori to regulate human cells.

PMID- 17538877
TI  - Late postnatal transmission of HIV-1 and associated factors.
AB  - BACKGROUND: The present study was undertaken to determine the risk and timing of
      late postnatal transmission (LPT) of human immunodeficiency virus type 1 (HIV-1).
      METHODS: Breast-fed infants previously enrolled in 2 trials of antiretroviral
      prophylaxis were monitored in Malawi. Kaplan-Meier and proportional hazard models
      assessed cumulative incidence and association of factors with LPT. RESULTS:
      Overall, 98 infants were HIV infected, and 1158 were uninfected. The cumulative
      risk of LPT at age 24 months was 9.68% (95% confidence interval, 7.80%-11.56%).
      The interval hazards at 1.5-6, 6-12, 12-18, and 18-24 months were 1.22%, 4.05%,
      3.48%, and 1.27%, respectively. CONCLUSIONS: The risk of LPT beyond 6 months is
      substantial. Weaning at 6 months could prevent >85% of LPT.

PMID- 17538878
TI  - Effects of nevirapine, compared with lamivudine, on lipids and lipoproteins in
      HIV-1-uninfected newborns: the stopping infection from mother-to-child via breast
      feeding in Africa lipid substudy.
AB  - BACKGROUND: The objective of the present study was to assess whether the high
      density lipoprotein cholesterol (HDL-c)-increasing effect of nevirapine (NVP), as
      observed in human immunodeficiency virus type 1 (HIV-1)-infected subjects, at
      least in part may relate to intrinsic properties of NVP. METHODS: At 2, 6, and 12
      weeks after birth, complete lipid profiles as well as plasma apolipoproteins
      levels were assessed in 80 HIV-uninfected newborns, half of whom received NVP and
      half lamivudine (3TC), respectively. Newborns were randomly selected from a
      randomized trial in which NVP or 3TC had been administered to HIV-uninfected
      infants born to HIV-infected mothers to try and prevent HIV-1 transmission from
      occurring during breast-feeding. RESULTS: After 6 weeks of therapy, the expected
      physiological decline in HDL-c levels in the newborns was attenuated in infants
      treated with NVP, compared with levels in those treated with 3TC. Apolipoprotein
      A-I (apoA-I) levels were higher at all time points in the NVP arm than they were
      in the 3TC arm (P=.02), reaching peak levels at 6 weeks. The difference in HDL-c
      was no longer significant at 12 weeks. CONCLUSIONS: apoA-I levels and HDL-c were
      elevated in HIV-1-uninfected newborns receiving NVP, compared with those
      receiving 3TC. These data support that NVP may indeed have intrinsic apoA-I and
      HDL-c elevating properties in humans.

PMID- 17538879
TI  - Virologic response to potent antiretroviral therapy and modeling of HIV dynamics
      in early pediatric infection.
AB  - BACKGROUND: Human immunodeficiency virus (HIV) infection in infancy features a
      persistently high viral load and elevated antiretroviral drug clearance rates,
      which pose significant therapeutic challenges to the clinician. Viral and
      cellular kinetic analyses performed in HIV-infected adults have yielded
      significant insights into the dynamic setting of this viral infection. Similar
      studies are needed in pediatric populations, in whom differing dynamics might
      translate into age-specific treatment approaches. METHODS: Viral and cellular
      kinetic analyses were performed using a nonlinear mixed-effects model in a cohort
      of 48 infants 1-24 months of age enrolled in a trial of ritonavir-based highly
      active antiretroviral therapy (HAART). RESULTS: Infected cell compartment
      kinetics were comparable with reported adult values, with no age-specific
      differences demonstrated--suggesting the ability to suppress viral replication in
      infants receiving HAART. Comparisons between 2 ritonavir dosing schedules
      revealed significant improvement in phase 1/2 decay constants in favor of the
      higher dose. A negative correlation was established between plasma RNA levels and
      phase 1 decay rates, which has worrisome implications for infant therapeutics
      given high infant pretreatment plasma virus levels. CONCLUSIONS: Ritonavir-based
      HAART regimens in infancy result in HIV decay constants comparable to those
      reported in adults, without age-specific variability. Despite higher plasma HIV
      levels and CD4 lymphocyte counts in infancy, HAART can result in timely,
      effective control of viral replication.

PMID- 17538880
TI  - HIV, malaria, and infant anemia as risk factors for postneonatal infant mortality
      among HIV-seropositive women in Kisumu, Kenya.
AB  - BACKGROUND: HIV and malaria in sub-Saharan Africa are associated with poor
      pregnancy outcome and infant survival. We studied the association of placental
      malaria, infant malaria and anemia, and infant HIV status with postneonatal
      infant mortality (PNIM) among infants of HIV-seropositive women. METHODS: During
      1996-2001, infants born to 570 HIV-seropositive mothers in Kisumu, Kenya were
      monitored monthly for malaria (parasitemia or clinical malaria) and anemia
      (hemoglobin level <8 g/dL) and vital status. RESULTS: Thirty-nine deaths occurred
      among 112 HIV-positive infants (420/1000 live births [LBs] [95% confidence
      interval {CI}, 318-522 LBs]), and 36 occurred among 458 HIV-negative infants
      (99/1000 LBs [95% CI, 68-130 LBs]) (P<.001). In multivariate Cox regression
      analysis among HIV-negative infants, PNIM was associated with infant anemia
      (adjusted hazard ratio [AHR], 5.03 [95% CI, 1.97-12.81]) but not with placental
      malaria (AHR, 1.22 [95% CI, 0.50-2.95]) or infant malaria (AHR, 0.35 [95% CI,
      0.10-1.21]). Among HIV-positive infants, neither placental malaria (AHR, 0.34
      [95% CI, 0.10-1.10]) nor infant malaria (AHR, 0.31 [95% CI, 0.07-1.33]) or anemia
      (AHR, 1.07 [95% CI, 0.32-3.61]) was significantly associated with PNIM.
      CONCLUSION: In this study population, placental malaria and infant parasitemia
      were not risk factors for PNIM among infants of HIV-seropositive women. The
      prevention of infant anemia may decrease PNIM among HIV-negative infants of HIV
      seropositive women.

PMID- 17538881
TI  - CD16+ monocyte subset preferentially harbors HIV-1 and is expanded in pregnant
      Malawian women with Plasmodium falciparum malaria and HIV-1 infection.
AB  - In a cross-sectional study, monocyte subsets in placental, cord, and maternal
      peripheral blood from pregnant Malawian women with human immunodeficiency virus
      (HIV)-1 infection and/or malaria were analyzed. HIV-uninfected Malawian women had
      higher baseline proportions of CD16(+) monocytes than those reported for healthy
      adults in developed countries. Malaria was associated with an increase in the
      proportion of CD16(+) monocytes that was significant in women coinfected with HIV
      1. CD16(+) monocytes expressed higher CCR5 levels than did CD14(hi)/CD16(-)
      monocytes and were significantly more likely to harbor HIV-1. These data suggest
      a role for CD16(+) monocytes in the pathogenesis of maternal malaria and HIV-1
      infections.

PMID- 17538882
TI  - Glucocorticoid-induced tumor necrosis factor receptor family-related protein
      triggering enhances HIV-specific CD4+ T cell cytokine secretion and protects HIV
      specific CD4+ T cells from apoptosis.
AB  - Human immunodeficiency virus (HIV)-specific CD4(+) T cell cytokine secretion is
      characteristically weak during HIV infection, in part because HIV-specific CD4(+)
      T cells undergo massive apoptotic deletion. Glucocorticoid-induced tumor necrosis
      factor (TNF) receptor family-related (GITR) protein triggering enhances murine
      antigen-specific T cell cytokine secretion by protecting T cells from apoptosis.
      Therefore, we investigated the impact of GITR triggering on HIV-specific CD4(+) T
      cell cytokine secretion and on apoptosis of HIV-specific CD4(+) T cells. In HIV
      infected subjects, CD4(+) T cell surface expression of GITR was greater than that
      in uninfected control subjects, and phytohemagglutinin induction of additional
      GITR expression was impaired. However, antibody triggering of GITR significantly
      increased HIV-specific CD4(+) T cell expression of TNF- alpha and interferon
      (IFN)- gamma . The percentage increase in HIV-specific CD4(+) T cell expression
      of TNF- alpha correlated directly with the absolute peripheral CD4(+) T cell
      count. Furthermore, GITR triggering reduced the expression of intracellular
      activated caspase-3 in HIV-specific CD4(+) T cells. Taken together, these data
      suggest that, despite abnormal GITR expression during HIV infection, GITR
      triggering enhances HIV-specific CD4(+) T cell cytokine expression and protects
      HIV-specific CD4(+) T cells from apoptosis.

PMID- 17538883
TI  - Evolution of HIV-1 in an HLA-B*57-positive patient during virologic escape.
AB  - Elite suppressors maintain normal CD4(+) T cell counts and viral loads of <50
      copies of human immunodeficiency virus type 1 (HIV-1) RNA per milliliter of
      plasma without antiviral therapy. We report here a case of virologic escape in a
      human leukocyte antigen (HLA)-B*57-positive patient shortly after seroconversion.
      This escape was associated with the development of mutations in 2 HLA-B*57
      restricted CD8(+) T cell Gag epitopes, reversion of the drug-resistance mutation
      M184V, and reversion of a novel polymorphism in Vpu. The present study suggests
      that control of viral replication in elite suppressors may be due to HIV-1
      specific CD8(+) T cells and, in some cases, mutations that have subtle effects on
      viral fitness.

PMID- 17538884
TI  - Gene expression correlates of postinfective fatigue syndrome after infectious
      mononucleosis.
AB  - BACKGROUND: Infectious mononucleosis (IM) commonly triggers a protracted
      postinfective fatigue syndrome (PIFS) of unknown pathogenesis. METHODS: Seven
      subjects with PIFS with 6 or more months of disabling symptoms and 8 matched
      control subjects who had recovered promptly from documented IM were studied. The
      expression of 30,000 genes was examined in the peripheral blood by microarray
      analysis in 65 longitudinally collected samples. Gene expression patterns
      associated with PIFS were sought by correlation with symptom factor scores.
      RESULTS: Differential expression of 733 genes was identified when samples
      collected early during the illness and at the late (recovered) time point were
      compared. Of these genes, 234 were found to be significantly correlated with the
      reported severity of the fatigue symptom factor, and 180 were found to be
      correlated with the musculoskeletal pain symptom factor. Validation by analysis
      of the longitudinal expression pattern revealed 35 genes for which changes in
      expression were consistent with the illness course. These genes included several
      that are involved in signal transduction pathways, metal ion binding, and ion
      channel activity. CONCLUSIONS: Gene expression correlates of the cardinal
      symptoms of PIFS after IM have been identified. Further studies of these gene
      products may help to elucidate the pathogenesis of PIFS.

PMID- 17538885
TI  - Molecular epidemiology of adenovirus type 4 infections in US military recruits in
      the postvaccination era (1997-2003).
AB  - BACKGROUND: Military recruits are at a higher risk of respiratory infection than
      their civilian counterparts. Continuous outbreaks of adenovirus (Ad)-associated
      acute respiratory disease were documented among US trainees before the
      implementation of serotype 4 (Ad4) and serotype 7 vaccines in 1971. The
      discontinuation of Ad vaccination programs in 1999 precipitated the reemergence
      of Ad in training sites, with Ad4 accounting for 98% of all diagnosed cases.
      METHODS: A total of 724 Ad4 strains isolated from recruits presenting with
      febrile respiratory illness at 8 training sites nationwide between 1997 and 2003
      were genome typed by restriction enzyme analysis. RESULTS: Seven genome types
      were identified, all of which were distinct from the prototype Ad4p and the
      vaccine type 4p1. Results showed very different, and often stable, genome type
      distributions at different geographic sites, despite the homogeneity of the
      recruit source population. CONCLUSIONS: The data support the hypothesis that
      reservoirs for Ad outbreaks are within recruit training sites or in their
      immediate environments, not in the incoming recruit population. Molecular
      characterization beyond serotype is critical to understanding the transmission
      dynamics of Ad infection in these unique susceptible populations and to the
      implementation of effective prevention approaches.

PMID- 17538886
TI  - Use of DNA tests for human Papillomavirus infection by US clinicians, 2004.
AB  - Since 1999, human papillomavirus (HPV) DNA tests have been approved only for
      abnormal cervical cytology management and as an adjunct to cervical cytology
      screening. To assess HPV DNA testing practices, we mailed surveys to 6906
      randomly selected clinicians in mid-2004. Awareness (87%) and ever use (67%) of
      HPV DNA tests was high. Test users were more likely than nonusers to be
      obstetricians/gynecologists or midwives, to be female, and to serve mainly
      privately insured patients. Respondents reported ever using HPV DNA tests for
      both approved and nonapproved indications, which included testing for HPV
      infection in women with anogenital warts or other sexually transmitted diseases,
      in their sex partners, and in men. Interventions are needed to discourage HPV DNA
      test use for nonapproved indications.

PMID- 17538887
TI  - HLA polymorphisms and cervical human Papillomavirus infection in a cohort of
      Montreal University students.
AB  - BACKGROUND: Only a minority of women with human papillomavirus (HPV) infection
      eventually develop cervical cancer, which suggests that host immune mechanisms
      play a role in the disease. HLA polymorphisms have been linked to the risk of
      cervical cancer, but very little is known about the role that they play in the
      acquisition and persistence of HPV infection. METHODS: A cohort study of cervical
      HPV infections was used to examine the role that 5 HLA alleles (B*07, DQB1*03,
      DQB1*0602, DRB1*13, and DRB1*1501) play in determining the risk of HPV positivity
      and persistence in 524 female university students in Montreal. HPV positivity was
      determined by use of the MY09/11 polymerase-chain-reaction protocol. HLA alleles
      from purified DNA from cervical specimens were typed by use of a polymerase-chain
      reaction technique using sequence-specific primers. RESULTS: HLA DRB1*13 was
      associated with cumulative risk of HPV infections (odds ratio [OR], 1.7 [95%
      confidence interval {CI}, 1.0-2.8]), for oncogenic HPV (OR, 1.6 [95% CI, 0.9
      2.8]), and for HPV-16 (OR, 2.0 [95% CI, 0.9-4.4]). DQB1*03 was consistently
      associated with a lower cumulative risk of HPV infections, but this association
      was not statistically significant. None of the alleles affected the risk of HPV
      persistence. CONCLUSIONS: The results of this study support the hypothesis that
      certain HLA class II polymorphisms mediate genetic susceptibility to the
      acquisition of HPV infection.

PMID- 17538888
TI  - Cytomegalovirus UL97 kinase mutations that confer maribavir resistance.
AB  - The cytomegalovirus (CMV) UL97 kinase inhibitor maribavir (MBV) is undergoing
      clinical antiviral trials. Two clinical CMV isolates serially passaged in cell
      culture under MBV showed >20-fold increases in MBV resistance after the
      development of the UL97 mutation V353A in one of the isolates and of T409M in the
      other. Marker transfer studies confirmed that the V353A and T409M mutations
      conferred ~15-fold and ~80-fold increases, respectively, in MBV resistance
      without significantly affecting ganciclovir susceptibility. The 3 UL97 mutations
      now known to confer MBV resistance are located upstream of UL97 mutations linked
      to ganciclovir resistance, closer to kinase domains that are associated with
      adenosine triphosphate binding and phosphotransfer.

PMID- 17538889
TI  - Helicobacter pylori induces up-regulation of the epidermal growth factor receptor
      in AGS gastric epithelial cells.
AB  - BACKGROUND: Helicobacter pylori infection increases the risk of gastric
      carcinogenesis. The aim of the present study was to determine whether H. pylori
      could up-regulate the expression of the epidermal growth factor receptor (EGFR),
      a critical gene in the carcinogenic process. METHODS: AGS gastric epithelial
      cells were infected with cag(+) toxigenic or cag(-) nontoxigenic strains of H.
      pylori or isogenic mutants. EGFR protein expression was determined by Western
      blotting and immunofluorescence. EGFR mRNA levels were evaluated using real-time
      polymerase chain reaction. The signaling pathways leading to EGFR up-regulation
      were examined using the ERK1/2 inhibitor PD98059, the Src inhibitor pp2, the
      nuclear factor- kappa B inhibitor caffeic acid phenethyl ester, EGFR neutralizing
      antibodies, and the EGFR kinase inhibitor AG1478. RESULTS: Infection of AGS cells
      by H. pylori significantly increased EGFR mRNA and protein levels. We found that
      this effect was limited to cag(+) H. pylori strains and that mutants with a
      defective type IV secretion system were unable to cause EGFR up-regulation.
      Increased EGFR expression was found to be dependent on EGFR receptor
      transactivation, ERK1/2 phosphorylation, and Src activation. CONCLUSION:
      Infection of gastric epithelial cells by H. pylori triggers an autocrine loop
      whereby EGFR transactivation leads to the up-regulation of EGFR expression. This,
      in turn, may contribute to unrestrained epithelial cell proliferation and
      carcinogenesis.

PMID- 17538890
TI  - Predictors of pneumococcal conjugate vaccine immunogenicity among infants and
      toddlers in an American Indian PnCRM7 efficacy trial.
AB  - BACKGROUND: Pneumococcal conjugate vaccines are important for the prevention of
      serious illness and death among infants. Factors associated with pneumococcal
      conjugate vaccine immunogenicity have not been explored. METHODS: Children <24
      months of age received 2, 3, or 4 doses of 7-valent pneumococcal conjugate
      vaccine (PnCRM7) or control vaccine depending on age at enrollment. Serum samples
      were tested for serotype-specific antibodies by enzyme-linked immunosorbant
      assay. Multiple linear regression was used to determine predictors of
      immunogenicity. RESULTS: Among 315 PnCRM7-vaccinated subjects and 295 control
      subjects enrolled at <7 months of age, geometric mean concentrations (GMCs) of
      antibodies were significantly higher after dose 3 than after dose 2 for all
      serotypes except type 4. The proportion of subjects with antibody concentrations
      > or =5.0 micro g/mL was higher for all serotypes, but the proportion with
      concentrations > or =0.35 micro g/mL was higher only for types 6B and 23F. Three
      dose and 2-dose regimens for those 7-11 and 12-23 months of age, respectively,
      were highly immunogenic. Increased maternal antibody concentrations were
      associated with reduced responses to dose 1 and 3 but not to dose 4 of PnCRM7.
      CONCLUSIONS: Maternal antibody is associated with a reduced infant response to
      PnCRM7 but does not interfere with immune memory. In infants, a third priming
      dose increases the antibody GMC and the proportion achieving an antibody
      concentration > or =5.0 micro g/mL but has little impact on the proportion
      achieving a concentration > or =0.35 micro g/mL.

PMID- 17538891
TI  - C1 inhibitor treatment improves host defense in pneumococcal meningitis in rats
      and mice.
AB  - In spite of antibiotic treatment, pneumococcal meningitis continues to be
      associated with significant morbidity and mortality. The complement system is a
      key component of innate immunity against invading pathogens. However, activation
      of complement is also involved in tissue damage, and complement inhibition by C1
      inhibitor (C1-inh) is beneficial in animal models of endotoxemia and sepsis. In
      the present study, we demonstrate classical pathway complement activation during
      pneumococcal meningitis in rats. We also evaluate the effect of C1-inh treatment
      on clinical illness, bacterial clearance, and inflammatory responses in rats and
      mice with pneumococcal meningitis. C1-inh treatment was associated with reduced
      clinical illness, a less-pronounced inflammatory infiltrate around the meninges,
      and lower brain levels of proinflammatory cytokines and chemokines. C1-inh
      treatment increased bacterial clearance, possibly through an up-regulation of
      CR3. Hence, C1-inh may be a useful agent in the treatment of pneumococcal
      meningitis.

PMID- 17538892
TI  - Binding of human factor H-related protein 1 to serum-resistant Borrelia
      burgdorferi is mediated by borrelial complement regulator-acquiring surface
      proteins.
AB  - BACKGROUND: Isolates of Borrelia burgdorferi, the causative agent of Lyme
      disease, express up to 5 distinct complement regulator-acquiring surface proteins
      (CRASP-1, -2, -3, -4, and -5). METHODS: By use of ligand affinity blotting,
      enzyme-linked immunosorbent assay, surface plasmon resonance, and functional
      complement assays, we have identified factor H-related protein 1 (FHR-1) as a
      novel protein that binds to the bacterium via CRASP-3, -4, and -5. RESULTS: When
      incubated in serum, serum-resistant Borrelia burgdorferi strain LW2 bind FHR-1,
      an additional member of the human factor H protein family, and, similarly, 2
      mouse FHR proteins bind to the surface. Recombinant FHR-1 binds to 3 borrelial
      surface proteins (CRASP-3, -4, and -5) but not to CRASP-1 and -2. A comparative
      analysis of the individual CRASPs revealed common as well as distinct binding
      profiles for the 3 human regulators. FHR-1 binds to 3 CRASPs, and factor H binds
      to all 5 CRASPs. In addition, factor H-like protein 1 interacts with CRASP-1 and 
      2 but with no other borrelial proteins. CONCLUSIONS: Thus, by expressing multiple
      surface proteins with different binding properties, the pathogen can attach a
      unique combination of host complement regulators to its surface. For the
      pathogen, this type of surface decoration and specific acquisition of different
      host plasma proteins allows fine-tuning of the host immune attack.

PMID- 17538893
TI  - Francisella tularensis has a significant extracellular phase in infected mice.
AB  - The ability of Francisella tularensis to replicate in macrophages has led many
      investigators to assume that it resides primarily intracellularly in the blood of
      mammalian hosts. We have found this supposition to be untrue. In almost all
      cases, the majority of F. tularensis recovered from the blood of infected mice
      was in plasma rather than leukocytes. This distribution was observed irrespective
      of size of inoculum, route of inoculation, time after inoculation, or virulence
      of the infecting strain. Our findings yield new insight into the pathogenesis of
      tularemia and may have important ramifications in the search for anti-Francisella
      therapies.

PMID- 17538894
TI  - Children in Burkina Faso who are protected by insecticide-treated materials are
      able to clear drug-resistant parasites better than unprotected children.
AB  - BACKGROUND: It has been suggested that reducing exposure to malaria by vector
      control might impair the development of naturally acquired immunity to malaria.
      It is also thought that an individual's ability to clear drug-resistant malarial
      parasites after treatment is enhanced by acquired immunity. METHODS: To
      investigate the hypothesis that insecticide-treated materials may affect the
      acquisition of immunity to malaria, we compared the ability of children living in
      villages in which insecticide-treated curtains (ITCs) had been used for 6-8 years
      to clear resistant parasites after treatment with chloroquine (CQ) with that of
      children living in unprotected villages. RESULTS: A total of 1035 children aged 6
      59 months with falciparum malaria were treated with CQ; 409 were subsequently
      identified as carrying parasites with the pfcrt-76T allele. More children from
      ITC villages cleared parasites harboring this allele than did children from non
      ITC villages (34.1% vs. 24.0%; adjusted odds ratio [OR], 1.80 [95% confidence
      interval {CI}, 1.15-2.80]; P=.01). The difference in the clearance of parasites
      with the pfcrt-76T allele was seen in children aged 6-35 months (32.3% vs. 19.3%;
      adjusted OR, 2.34 [95% CI, 1.18-4.66]; P=.02) but not in older children (37.3%
      vs. 37.0%; adjusted OR, 1.09 [95% CI, 0.56-2.10]; P=.97). Rates of adequate
      clinical response among children carrying parasites with the pfcrt-76T allele
      were similar in ITC and non-ITC villages (75.1% vs. 68.6%; adjusted OR, 1.21 [95%
      CI, 0.61-2.39]; P=.58). CONCLUSION: Our data suggest that the children who were
      protected from malaria by ITCs acquired functional immunity more rapidly than did
      the control children.

PMID- 17538895
TI  - Safety and clinical outcome of experimental challenge of human volunteers with
      Plasmodium falciparum-infected mosquitoes: an update.
AB  - BACKGROUND: Challenge of volunteers by the bites of membrane-fed anopheline
      mosquitoes infected with Plasmodium falciparum was reported in 1986. In 1997, an
      analysis of experience with 118 volunteers indicated that mosquito inoculation of
      P. falciparum could be a safe, well-tolerated, reproducible, and efficient method
      of challenge. METHODS: We reviewed the records of 47 volunteers challenged at our
      institution with the NF54 isolate of P. falciparum between 1998 and 2002. We also
      reviewed data from 17 published studies of experimental challenge conducted since
      1996. RESULTS: At our institution, the time to onset of first symptoms
      (incubation period) was 8.9 days, and the time to first detectable parasitemia on
      blood smear (prepatent period) was 10.5 days. All volunteers became symptomatic.
      Most symptoms were mild to moderate, although 21% of volunteers had at least 1
      severe symptom. None developed complicated or severe malaria, and all were cured.
      Laboratory assessments demonstrated modest, short-term abnormalities typical of
      malaria. Review of 17 published studies demonstrated that an additional 367
      volunteers received experimental challenge safely with similar outcomes.
      CONCLUSIONS: In total, data from 532 volunteers demonstrate that experimental
      challenge is safe and results in predictable incubation and prepatent periods.
      Our findings support the continued use of this method for testing efficacy of
      vaccines and drugs against P. falciparum.

PMID- 17538896
TI  - Effects of sex, parity, and sequence variation on seroreactivity to candidate
      pregnancy malaria vaccine antigens.
AB  - BACKGROUND: Plasmodium falciparum-infected erythrocytes adhere to chondroitin
      sulfate A (CSA) to sequester in the human placenta, and pregnancy malaria (PM) is
      associated with the development of disease in and the death of both mother and
      child. A PM vaccine appears to be feasible, because women become protected as
      they develop antibodies against placental infected erythrocytes (IEs). Two IE
      surface molecules, VAR1CSA and VAR2CSA, bind CSA in vitro and are potential
      vaccine candidates. METHODS: We expressed all domains of VAR1CSA and VAR2CSA as
      mammalian cell surface proteins, using a novel approach that allows rapid
      purification, immobilization, and quantification of target antigen. For serum
      samples from East Africa, we measured reactivity to all domains, and we examined
      the effects of host sex and parity, as well as the effects of parasite antigenic
      variation. RESULTS: Serum samples obtained from multigravid women had a higher
      reactivity to all VAR2CSA domains than did those obtained from primigravid women
      or from men. Conversely, serum samples obtained from men had consistently higher
      reactivity to VAR1CSA domains than did those obtained from gravid women.
      Seroreactivity was strongly influenced by antigenic variation of VAR2CSA Duffy
      binding-like domains. CONCLUSIONS: Women acquire antibodies to VAR2CSA over
      successive pregnancies, but they lose reactivity to VAR1CSA. Serum reactivity to
      VAR2CSA is variant specific, and future studies should examine the degree to
      which functional antibodies, such as binding-inhibition antibodies, are variant
      specific.

PMID- 17538897
TI  - A shared Asian origin of the triple-mutant dhfr allele in Plasmodium falciparum
      from sites across Africa.
AB  - BACKGROUND: Usefulness of sulfadoxine-pyrimethamine as first-line therapy for
      uncomplicated Plasmodium falciparum malaria and intermittent preventive treatment
      in pregnancy throughout sub-Saharan Africa is compromised by the spread of dhfr
      alleles associated with pyrimethamine resistance. A predominant haplotype
      associated with the N51I+C59R+S108N triple-mutant dhfr allele has been reported
      recently in 4 African countries. A more comprehensive picture of the evolution of
      this mutant allele in Africa is lacking. METHODS: Seventy-five P. falciparum
      isolates carrying the wild-type dhfr allele and 204 carrying the triple-mutant
      dhfr allele from 11 African countries were selected. The genetic diversity of the
      chromosomes bearing these alleles was analyzed with 4 microsatellite markers
      closely linked to the dhfr gene. RESULTS: Seventy-three different 4-locus
      haplotypes carrying the wild-type dhfr allele were found. By contrast, 175 (85%)
      of 204 isolates carrying the triple-mutant dhfr allele shared a unique haplotype,
      identical to the one identified in Thailand. For the remaining triple-mutant
      isolates and one isolate with the quadruple-mutant dhfr allele
      (N51I+C59R+S108N+I164L), haplotypes were closely related to the predominant
      haplotype by mutation or recombination. CONCLUSIONS: Migration of parasites
      carrying an ancestral triple-mutant dhfr allele drives the spread of dhfr alleles
      associated with pyrimethamine resistance throughout West and Central Africa.

PMID- 17538898
TI  - Adeno-associated viral vector transduction of human mesenchymal stem cells.
AB  - Mesenchymal stem cells (MSCs) have received considerable attention in the
      emerging field of regenerative medicine. One aspect of MSC research focuses on
      genetically modifying the cells with the aim of enhancing their regenerative
      potential. Adeno-associated virus (AAV) holds promise as a vector for human gene
      therapy, primarily due to its lack of pathogenicity and low risk of insertional
      mutagenesis. However, the existing data pertaining to AAV transduction of MSCs is
      limited. The objective of this work was to examine the efficiency and kinetics of
      in vitro transduction using AAV serotype 2 in human MSCs and to assess whether
      AAV transduction affects MSC multipotentiality. The results indicated that human
      MSCs could indeed be transiently transduced in vitro by the AAV2 vector with
      efficiencies of up to 65%. The percentage of GFP-positive cells peaked at 4 days
      post-transduction and declined rapidly towards 0% after day 8. The level of
      transgene expression in the GFP-positive population increased 4-fold over a
      10,000 fold viral dose increase. This dose-response contrasted with the 200-fold
      increase observed in similarly transduced 293-cells, indicating a relatively
      restricted transgene expression in MSCs following AAV mediated gene delivery.
      Importantly, transduced MSCs retained multipotential activity comparable to
      untransduced controls.

PMID- 17538899
TI  - In-situ measurements of chondrocyte deformation under transient loading.
AB  - Chondrocytes are responsible for the elaboration and maintenance of the
      extracellular (EC) matrix in articular cartilage, and previous studies have
      demonstrated that mechanical loading modulates the biosynthetic response of
      chondrocytes in cartilage explants. The goal of this study is to investigate the
      deformation behaviour of the chondrocyte and its microenvironment under transient
      loading, in order to address the relationship between the applied dynamic
      deformation and cellular strain. In-situ strain measurements were performed on
      cells in the middle (MZ) zone at early time points during ramp loading and at
      equilibrium. In this study, we characterized the behaviour of cartilage at the
      zonal and cellular levels under compressive loading using digital image analysis
      on miniature samples tested in a custom microscopy-based loading device. The
      experimental results indicate that significant strain amplification occurs in the
      microenvironment of the cell, with the minimum (compressive) principal strain
      found to be nearly 7X higher in the intracellular region (IC), and ~5X higher in
      the pericellular (PC) matrix than in the EC matrix at peak ramp. A similar strain
      amplification mechanism was observed in the maximum (tensile) principal strain,
      and this behaviour persisted even after equilibrium was reached. The experimental
      results of this study were interpreted in the context of a finite element model
      of chondrocyte deformation, which modelled the cell as a homogeneous gel,
      possessing either a spherical or ellipsoidal geometry, surrounded by a semi
      permeable membrane, and accounted for the presence of a PC matrix. The results of
      the FEA demonstrate significant strain amplification mechanism in the IC region,
      greater than had previously been suggested in earlier computational studies of
      cell-EC matrix interactions. Based on the FEA, this outcome is understood to
      result from the large disparity between EC matrix and intracellular properties.
      The results of this study suggest that mechanotransduction of chondrocytes may be
      significantly mediated by this strain amplification mechanism during loading.

PMID- 17538918
TI  - Synthesis and electronic structure of a ferroborirene.

PMID- 17538919
TI  - Boron nitride nanomesh: functionality from a corrugated monolayer.

PMID- 17538920
TI  - Assembly of nanoparticle-protein binding complexes: from monomers to ordered
      arrays.

PMID- 17538921
TI  - Regioselective cysteine bioconjugation by appending a labeled cystein tag to a
      protein by using protein splicing in trans.

PMID- 17538922
TI  - On-column capture of a specific protein separated by SDS-CGE using an
      immunological reaction on magnetic beads.
AB  - The on-column capture of a specific protein using magnetic beads was applied to
      SDS-CGE. In a preliminary study, an immunological reaction in the presence of
      SDS, using a batch method, was attempted. Carbonic anhydrase (CA), alpha
      lactalbumin (LA), and HSA were denatured by heating in the presence of SDS and 2
      mercaptoethanol, and then reacted with anti-CA that had been immobilized on
      magnetic beads. Not only native CA, but also the denatured CA reacted with anti
      CA, even in the presence of SDS. Therefore, the on-column capture of denatured CA
      separated by SDS-CGE was attempted using a two-point detection technique. A
      mixture of proteins, containing LA, CA, and HSA, were separated by SDS-CGE
      according to their Mr. The CA was then specifically captured on anti-CA
      immobilized magnetic beads, which were packed between two detection windows in
      the capillary column, during the electrophoresis. The results show that the
      technique leads to information similar to that obtained by Western blotting,
      i.e., a protein can be identified by its Mr and reaction with its antibody.

PMID- 17538923
TI  - Cationic gemini surfactant as dynamic coating in CE for the control of EOF and
      wall adsorption.
AB  - The cationic gemini surfactant ethylene bis(1-dodecyldimethylammonium) dibromide
      was used as a dynamic coating to control EOF and prevent wall adsorption of basic
      proteins in CE for the first time. This gemini surfactant shows a more powerful
      capability in EOF reversal than traditional single-chained surfactant. The gemini
      surfactant reverses the EOF at a concentration level even less than 0.01 mM, and
      the EOF magnitude is affected by surfactant concentration, pH, ionic strength,
      and ions added in buffer. Highly efficient and rapid protein separation (N >
      300,000) was obtained with buffer containing 2 mM gemini surfactant under pH
      ranging from 3 to 6. The effects of surfactant and buffer concentration on
      protein separation were investigated in detail. Under the optimal conditions,
      good repeatability (RSD of migration time <0.6% for run-to-run and <2.5% for day
      to-day assays) and recovery (>90%) of tested proteins were obtained. This new
      dynamic coating is also suitable for biosample analysis.

PMID- 17538924
TI  - Amino acids: aspects of impurity profiling by means of CE.
AB  - Quality control of active pharmaceutical ingredients (API) is commonly performed
      by means of HPLC. However, CE offers a suitable alternative, especially for the
      analysis of easily chargeable substances, i.e., amino acids. The article reviews,
      on the one hand, CE methods developed for impurity profiling of synthesized amino
      acid analogs. However, nowadays, production of amino acids/peptides is dominated
      by fermentation. Therefore, on the other hand, CE methods for the analysis of
      amino acids and small peptides are reported. The results of CE analysis of
      glutathione samples according to the monograph in the European Pharmacopoeia (Ph.
      Eur.) 5.7 and amino acid samples after derivatization with 9-fluorenylmethyl
      chloroformate (FMOC) and 3-(4-carboxybenzoyl)quinoline-2-carboxaldehyde (CBQCA)
      may pave the way for impurity profiling of fermentatively produced API by means
      of CE.

PMID- 17538925
TI  - Analysis of amino acids by combination of carrier ampholyte-free IEF with ITP.
AB  - The use of carrier ampholyte-free IEF (CAF-IEF) with ITP mobilization and
      conductivity detection in ITP mode for preconcentration and analysis of amino
      acids is demonstrated. The analytical procedure consists of three subsequent
      steps. In the first step, amino acids are continuously dosed from an infinite
      volume reservoir by electromigration to the column, where a sharp, stationary
      neutralization reaction boundary (NRB) is created in between acidic and basic
      primary electrolyte. Here, amino acids are selectively focused (trapped), if
      their pI falls to the pH difference on both sides of the NRB (pH gap). Amino
      acids create sharp rectangular zones, arranged according to their pI values. In
      the second step, focused zones are mobilized. After accumulation of the
      detectable amount of amino acids, dosing electrolyte in the infinite volume
      reservoir is changed for the mobilizing electrolyte. The migration mode is
      changed from CAF-IEF to ITP and substances start to migrate toward the analytical
      capillary. In the third step, analytes are transferred into the analytical column
      equipped with a conductivity detector and are detected in the new leading
      electrolyte in an ITP migration mode. The presented CAF-IEF-ITP-ITP with time
      dependent accumulation of the large-volume sample enables to achieve in a
      reasonable time a 100 times lower c-LOD (here in orders of nmol/L), than can be
      reached by conventional hyphenated ITP-ITP.

PMID- 17538926
TI  - Profiling recombinant major birch pollen allergen Bet v 1a and carbamylated
      variants with CZE and CIEF.
AB  - A preparation of recombinant birch pollen allergen of Betula verrucosa isoform 1a
      (Bet v 1a) containing chemically modified (carbamylated) variants has been
      analyzed by CZE and CIEF. In CZE, employing a 100 mmol/L MES buffer at pH 6.50,
      with 0.4 mmol/L tetraethylenepentamine (TEPA) added, allowed for the resolution
      of 17 protein fractions. The CIEF profiling of the allergen preparation required
      a combination of a wide-pH-range carrier ampholyte (CA) of pH 3-10 with two
      narrow-range CAs of pH 5-6 and 5-7. For CIEF, 91 mmol/L of glycine at pH 2.12 and
      20 mmol/L of CHES at pH 10.00 were applied as anolyte and catholyte,
      respectively. The generated pH gradient was nonlinear with a flat slope for pH 4
      6, thus providing an improved resolution. In CIEF, up to 18 protein fractions
      were distinguished as well. The pI of the target allergen Bet v 1a was 4.9 as
      determined by means of two pI marker compounds flanking the allergen. Relative
      purity of the target allergen within the preparation containing carbamylated
      variants was in accordance for both separation systems and varied between 40.7
      and 42.8%.

PMID- 17538927
TI  - A chemiluminescence-based assessment of androgen-binding activity in a large
      pedigree affected with androgen insensitivity syndrome.
AB  - We report a novel chemiluminescence (CL)-based method for assaying the ligand
      binding activity of the androgen receptor. The central parts of this method are
      the utilization of the steroid CL marker as the replacement of the radioactive
      label in the conventional ligand-binding assay and the determination of the
      binding activity by the light measurement of the bound CL-label under an H(2)O(2)
      microperoxidase system. The properties and reliability of this assay were
      investigated and verified using genital skin fibroblasts (GSF) from seven normal
      males. The method is precise (CV < 7% for both B(max) and K(d)) with high
      correlation coefficients (r > 0.93) in each Scatchard linear regression analysis.
      This assay can determine the androgen binding properties using only a quarter of
      the cells (approximately 40 000 cells/data point) of that required by the
      radiolabelling approach. The utility of the method was illustrated by binding
      experiment on the GSFs of several patients from a large Chinese family affected
      with androgen insensitivity syndrome. The familial distinct feature is that all
      patients shared an identical Arg840Cys substitution in the androgen receptor but
      displayed high phenotypic variation in disorders of male sexual development. The
      patients selected for the present study represent a wide spectrum of this
      phenotypic variation. This study thus provides insights on the pleiotropic
      effects of the mutation. In conclusion, the CL-based method can serve as an
      effective, precise and reliable replacement for the radiolabelling approach and
      has the advantages of simplicity, cost-effectiveness and health and environmental
      safety over the counterpart.

PMID- 17538928
TI  - 4-phenylbutyrate enhances the cell surface expression and the transport capacity
      of wild-type and mutated bile salt export pumps.
AB  - Progressive familial intrahepatic cholestasis type 2 (PFIC2) is caused by a
      mutation in the bile salt export pump (BSEP/ABCB11) gene. We previously reported
      that E297G and D482G BSEP, which are frequently found mutations in European
      patients, result in impaired membrane trafficking, whereas both mutants retain
      their transport function. The dysfunctional localization is probably attributable
      to the retention of BSEP in endoplasmic reticulum (ER) followed by proteasomal
      degradation. Because sodium 4-phenylbutyrate (4PBA) has been shown to restore the
      reduced cell surface expression of mutated plasma membrane proteins, in the
      current study, we investigated the effect of 4PBA treatment on E297G and D482G
      BSEP. Transcellular transport and cell surface biotinylation studies using Madin
      Darby canine kidney (MDCK) II cells demonstrated that 4PBA treatment increased
      functional cell surface expression of wild-type (WT), E297G, and D482G BSEP. The
      prolonged half-life of cell surface-resident BSEP with 4PBA treatment was
      responsible for this result. Moreover, treatment of Sprague-Dawley rats with 4PBA
      resulted in an increase in BSEP expression at the canalicular membrane, which was
      accompanied by an increase in the biliary excretion of [(3)H]taurocholic acid
      (TC). CONCLUSION: 4PBA treatment with a clinically achievable concentration
      enhances the cell surface expression and the transport capacity of WT, E297G, and
      D482G BSEP in MDCK II cells, and also induces functional BSEP expression at the
      canalicular membrane and bile acid transport via canalicular membrane in vivo.
      4PBA is a potential pharmacological agent for treating not only PFIC2 patients
      with E297G and D482G mutations but also other cholestatic patients, in whom the
      BSEP expression at the canalicular membrane is reduced.

PMID- 17538929
TI  - Mitochondrial hepatopathies: advances in genetics and pathogenesis.
AB  - Hepatic involvement is a common feature in childhood mitochondrial hepatopathies,
      particularly in the neonatal period. Respiratory chain disorders may present as
      neonatal acute liver failure, hepatic steatohepatitis, cholestasis, or cirrhosis
      with chronic liver failure of insidious onset. In recent years, specific
      molecular defects (mutations in nuclear genes such as SCO1, BCS1L, POLG, DGUOK,
      and MPV17 and the deletion or rearrangement of mitochondrial DNA) have been
      identified, with the promise of genetic and prenatal diagnosis. The current
      treatment of mitochondrial hepatopathies is largely ineffective, and the
      prognosis is generally poor. The role of liver transplantation in patients with
      liver failure remains poorly defined because of the systemic nature of the
      disease, which does not respond to transplantation. Prospective, longitudinal,
      multicentered studies will be needed to address the gaps in our knowledge in
      these rare liver diseases.

PMID- 17538930
TI  - Tissue-type plasminogen activator deficiency exacerbates cholestatic liver injury
      in mice.
AB  - Recent studies demonstrating a role for plasminogen activator inhibitor (PAI)-1
      in cholestatic liver disease in mice suggested that tissue-type plasminogen
      activator (tPA) or urokinase plasminogen activator (uPA) might be important after
      biliary tract obstruction. We now demonstrate that blocking tPA exacerbates liver
      injury after bile duct ligation (BDL). tPA deficient mice have increased bile
      infarcts, increased TUNEL positive cells, increased neutrophil infiltration,
      reduced hepatocyte proliferation and reduced ductular reaction 72 hours after BDL
      compared to wild type mice. In addition, the protective and proliferative effects
      of plasminogen activator inhibitor 1 (PAI-1) deficiency after BDL are
      dramatically blocked by the tPA inhibitor tPA-STOP. One potential mechanism for
      these effects is that both tPA deficiency and tPA-STOP reduce hepatocyte growth
      factor (HGF) activation and c-Met phosphorylation in the liver after BDL. In
      support of this hypothesis, HGF treatment reverses the effects of tPA deficiency
      in mice. Furthermore, preferential tPA activation in areas of injury after BDL
      might occur because fibrin accumulates in bile infarcts and activates tPA.
      CONCLUSION: tPA inactivation accelerates liver injury after BDL and reduces HGF
      activation. These data suggest that strategies to increase HGF activation might
      be protective in liver diseases with biliary tract obstruction even without
      increased HGF production.

PMID- 17538931
TI  - Immunoglobulin G4 associated cholangitis: description of an emerging clinical
      entity based on review of the literature.

PMID- 17538932
TI  - HIV and liver disease forum: conference proceedings.

PMID- 17538933
TI  - Restoration of p53 function: a new therapeutic strategy to induce tumor
      regression?
AB  - Although cancer arises from a combination of mutations in oncogenes and tumour
      suppressor genes, the extent to which tumour suppressor gene loss is required for
      maintaining established tumours is poorly understood. p53 is an important tumour
      suppressor that acts to restrict proliferation in response to DNA damage or
      deregulation of mitogenic oncogenes, by leading to the induction of various cell
      cycle checkpoints, apoptosis or cellular senescence. Consequently, p53 mutations
      increase cell proliferation and survival, and in some settings promote genomic
      instability and resistance to certain chemotherapies. To determine the
      consequences of reactivating the p53 pathway in tumours, we used RNA interference
      (RNAi) to conditionally regulate endogenous p53 expression in a mosaic mouse
      model of liver carcinoma. We show that even brief reactivation of endogenous p53
      in p53-deficient tumours can produce complete tumour regressions. The primary
      response to p53 was not apoptosis, but instead involved the induction of a
      cellular senescence program that was associated with differentiation and the
      upregulation of inflammatory cytokines. This program, although producing only
      cell cycle arrest in vitro, also triggered an innate immune response that
      targeted the tumour cells in vivo, thereby contributing to tumour clearance. Our
      study indicates that p53 loss can be required for the maintenance of aggressive
      carcinomas, and illustrates how the cellular senescence program can act together
      with the innate immune system to potently limit tumour growth.

PMID- 17538934
TI  - T cells in the liver: there is life beyond the graveyard.
AB  - Influenza A virus infection of C57BL/6 mice is a well-characterized model for
      studying CD8+ T cell-mediated immunity. Analysis of primary and secondary
      responses showed that the liver is highly enriched for CD8+ T cells specific for
      the immunodominant H2D(b)NP(366-374) (D(b)NP(366)) epitope. Functional analysis
      established that these liver-derived virus-specific CD8+ T cells are fully
      competent cytotoxic effectors and IFN-gamma secretors. In addition, flow
      cytometric analysis of early apoptotic cells showed that these influenza-specific
      CD8+ T cells from liver are as viable as those in the spleen, bronchoalveolar
      lavage, mediastinal lymph nodes, or lung. Moreover, cytokine profiles of the
      influenza-specific CD8+ T cells recovered from different sites were consistent
      with the bronchoalveolar lavage, rather than liver population, being the most
      susceptible to activation-induced cell death. Importantly, adoptively transferred
      influenza virus-specific CD8+ T cells from the liver survived and were readily
      recalled after virus challenge. Together, these results show clearly that the
      liver is not a "graveyard" for influenza virus-specific CD8+ T cells.

PMID- 17538935
TI  - Anti-gp210 antibody mirrors disease severity in primary biliary cirrhosis.

PMID- 17538937
TI  - Which gene, Reg2 or Reg3beta, was targeted that affected liver regeneration?

PMID- 17538939
TI  - APRI-M6 for predicting long-term outcome of chronic hepatitis C patients after
      interferon-based therapy: more questions than answers.

PMID- 17538940
TI  - Self-monitoring of blood glucose in type-2 diabetes: what is the evidence?
AB  - BACKGROUND: There is a controversy about self-monitoring of blood glucose (SMBG)
      in patients with type 2 diabetes who are not using insulin. Randomized trials are
      limited in duration, size, and validity. METHODS: Systematic search for
      randomized trials and observational studies published since 1990. For inclusion
      studies had to report on SMBG in type 2 diabetes managed with oral hypoglycaemic
      agents and/or diet alone, HbA(1c) or clinical outcome, have at least 50 patients
      and be of at least 6 months' duration. RESULTS: Three randomized trials with 1000
      patients were included, though all had interventions differing in the amount of
      education on SMBG, and in the population studied. The two larger studies had
      statistically significantly lower HbA(1c) levels with SMBG. Thirteen
      observational studies had information on over 60,000 patients. Smaller studies
      had lower initial HbA(1c) and showed no association between SMBG and laboratory
      or clinical improvement. Larger studies tended to have higher initial HbA(1c) and
      did show an association between SMBG and laboratory or clinical improvement.
      Overall, improvement in glycaemic control with SMBG tended to be seen in studies
      with initial HbA(1c) above 8%. CONCLUSIONS: It is likely that SMBG is beneficial
      in some circumstances, for example as an educational tool, for patients with type
      2 diabetes not using insulin who have poor glycaemic control. More information is
      needed at the level of the individual patient, rather than group means, and about
      timing and frequency of monitoring, response to those results, what constitutes
      effective patient education, and long-term clinical outcomes.

PMID- 17538941
TI  - The different mechanisms of insulin sensitizers to prevent type 2 diabetes in
      OLETF rats.
AB  - OBJECTIVE: To investigate the effects of pioglitazone and metformin treatment
      during pre-diabetic period for the prevention of diabetes in a rat model.
      METHODS: OLETF rats aged 18-weeks, were treated with pioglitazone (10 mg/kg/day)
      and metformin (300 mg/kg/day) for 10 weeks from their pre-diabetic period. We
      measured weight, lipid profiles, fat distribution, glucose tolerance, and
      pancreatic insulin content. RESULTS: Prominent weight gain (mostly subcutaneous
      fat area) was observed in the pioglitazone-treated OLETF (O-P) rats versus
      significant weight loss was observed in the metformin-treated OLETF (O-M) rats.
      Pioglitazone reversed the serum triglyceride (TG) and FFAs levels to normal (TG
      0.46 +/- 0.04 vs 0.88 +/- 0.05 mmol/l in LETO). At the age of 28 weeks, the O-P
      rats showed completely normal glucose tolerance, and the glucose disposal rate
      (GDR) was markedly improved (25.6 +/- 0.4 vs 20.6 +/- 0.5 mg/min/kg in O-C, p <
      0.05). The O-M rats also showed an improved fasting glucose and GDR level, but
      not as much as those with O-P rats. The pancreas insulin contents were much
      improved in the O-P rats (22.9 +/- 1.2 vs 18.8 +/- 1.3 nmol/pancreas in O-M rats,
      p < 0.05) with histological improvement. CONCLUSION: The pre-diabetic treatment
      with pioglitazone, despite significant weight gain, completely prevents to
      develop diabetes and enhances beta cell function with preservation of islet cell
      changes. Metformin treatment was also effective, but mainly by ameliorating the
      insulin resistance with marked reduction in body weight. The reversal of
      dyslipidaemia and the fat redistribution might contribute to the greater
      improvement of pioglitazone treatment compared to metformin in OLETF rats.

PMID- 17538942
TI  - Global benefit-risk assessment in designing clinical trials and some statistical
      considerations of the method.
AB  - When characterizing a therapy, the efficacy and the safety are two major aspects
      under consideration. In prescribing a therapy to a patient, a clinician puts the
      two aspects together and makes a decision based on a consolidated thought
      process. The global benefit-risk (GBR) measures proposed by Chuang-Stein et al.
      (Stat. Med. 1991; 10:1349-1359) are useful in facilitating the thinking, and
      creating the framework for making statistical comparisons based on benefit-risk
      point of view. This article describes how a GBR linear score was defined and used
      as the primary outcome measure in a clinical trial design. The robustness of the
      definitions of 'benefit' and 'risk' are evaluated using different criteria. The
      sensitivity of the pre-specified weights is also analyzed using alternative
      weights; one of those was determined by the relative to an identified
      distribution integral transformation approach (Biometrics 1958; 14:18-38).
      Statistical considerations are illustrated using pooled data from clinical trials
      studying antidepressant. The pros and cons for using GBR assessments in the
      setting of clinical trials are discussed.

PMID- 17538943
TI  - The high-risk benign tumor: evidence from the two-stage skin cancer model and
      relevance for human cancer.
AB  - Benign tumors that form following chemical initiation and promotion in the mouse
      skin can be grouped into two classes. The majority of papillomas do not progress
      to squamous cell carcinoma (SCC), and these are designated as low-risk or
      terminally benign papillomas. In contrast, a much smaller group forms the true
      precursor to the SCC, and these have a significantly higher frequency and rate of
      malignant conversion than the bulk of low-risk papillomas. In standard two-stage
      carcinogenesis studies both tumor types are present, but grossly
      indistinguishable. Here we describe properties and potential origins of high-risk
      papillomas and discuss the relevance of this model for certain human cancers with
      defined premalignant states.

PMID- 17538944
TI  - Cooperation of Ha-ras and Bcl-2 during multistep skin carcinogenesis.
AB  - Nonmelanoma skin cancer (NMSC) is the most frequently diagnosed cancer in the
      United States. Deregulation of bcl-2 and ras family members is commonly observed
      in NMSC. It has been previously demonstrated that simultaneous bcl-2 and Ha-ras
      gene expression in keratinocytes results in disordered differentiation and
      resistance to cell death induced by ultraviolet (UV) radiation. It was,
      therefore, interest to assess the extent of cooperation between bcl-2 and Ha-ras
      during multistep skin carcinogenesis. The keratin 1 promoter was used to generate
      HK1.ras and HK1.bcl-2 transgenic mice, which were subsequently crossed to
      generate HK1.ras/bcl-2 double transgenic mice. The apoptotic index (AI) following
      UV-irradiation was significantly lower in HK1.bcl-2 and HKI.ras/bcl-2 epidermis
      compared to control littermates. Interestingly, the AI of HK1.ras/bcl-2 mice was
      significantly lower than even HK1.bcl-2 mice following UV-irradiation. To
      investigate the interaction of these oncogenes in skin tumorigenesis, a two-stage
      chemical carcinogenesis protocol was used to induce tumors. The individual
      contributions of Ha-ras and bcl-2 to papilloma latency, incidence, and growth
      rate in HK1.ras/bcl-2 double transgenic mice was marginally additive. Papillomas
      arising in HK1.ras transgenic mice exhibited the highest rate of apoptosis
      whereas papillomas arising in the HK1.ras/bcl-2 double transgenic mice exhibited
      rates of apoptosis that were significantly lower than papillomas arising in
      either control littermate or HK1.ras mice. Constitutive expression of either Ha
      ras or bcl-2 exhibited similar rates of malignant tumor progression and they were
      not significantly different than control littermates. Importantly, when these two
      oncoproteins were coexpressed, a significant, and synergistic, increase in
      malignant transformation was observed.

PMID- 17538945
TI  - Progressive up-regulation of genes encoding DNA methyltransferases in the
      colorectal adenoma-carcinoma sequence.
AB  - Epigenetic silencing is a prominent feature of cancer. Here, we investigated the
      expression of DNA demethylase and three DNA methyltransferases during colorectal
      tumorigenesis comparing the genes encoding DNA methyltransferases 1 (DNMT1), 3A,
      and 3B (DNMT3A and DNMT3B) with methyl-CpG binding domain protein 2 (MBD2),
      recently described as the only active DNA demethylase. Total RNA isolated from
      normal colonic mucosa (n = 24), benign adenomas (n = 18), and malignant
      colorectal carcinomas (n = 32) was analyzed by reverse transcriptase-PCR with
      subsequent quantification by capillary gel electrophoresis. In contrast to MBD2,
      expression of DNMT1 and DNMT3A increased in parallel to the degree of dysplasia,
      with significant overexpression in the malignant lesion when compared with mucosa
      or with benign lesions (DNMT1). Pairwise comparisons between tumors and matched,
      adjacent healthy mucosa tissue (n = 13) revealed that expression of all three
      genes encoding DNA methyltransferases increased by two- to three-fold. Our data
      suggest a relevant role of the DNA methyltransferases during colorectal
      tumorigenesis. This increase is not counterbalanced by enhanced expression of the
      demethylating component MBD2. As a consequence, epigenetic regulation in the
      adenoma-carcinoma sequence may be driven by increased methylating activity rather
      than suppressed demethylation.

PMID- 17538946
TI  - Frequent hypermethylation of MST1 and MST2 in soft tissue sarcoma.
AB  - The RASSF1A tumor suppressor is involved in regulation of apoptosis and cell
      cycle progression. RASSF1A is localized to microtubules and binds the apoptotic
      kinases MST1 and MST2. It has been shown that this interaction is mediated by the
      Sav-RASSF-Hpo domain, which is an interaction domain characterized for the
      Drosophila proteins Sav (human WW45), Hpo (human MST1 and MST2) and Warts/LATS
      (large tumor suppressor). Previously, we have reported that RASSF1A
      hypermethylation occurs frequently in soft tissue sarcoma and is associated with
      an unfavorable prognosis for cancer patients. In our study, we performed
      methylation analysis of the CpG island promoter of MST1, MST2, WW45, LATS1 and
      LATS2 in soft tissue sarcomas by methylation-specific PCR. No or a very low
      methylation frequency was detected for WW45, LATS1 and LATS2 (<7%). In 19 out of
      52 (37%) sarcomas, a methylated promoter of MST1 was detected and 12 out of 60
      (20%) samples showed methylation of the MST2 promoter. Methylation status of MST1
      was confirmed by bisulfite sequencing. In tumors harboring a methylated promoter
      of MST1, a reduction of MST1 expression was observed by RT-PCR. In
      leiomyosarcomas, MST1 and MST2 or RASSF1A methylation were mutually exclusive (P
      = 0.007 and P = 0.025, respectively). Surprisingly, a significantly increased
      risk for tumor-related death was found for patients with an unmethylated MST1
      promoter (P = 0.036). In summary, our results suggest that alteration of the Sav
      RASSF1-Hpo tumor suppressor pathway may occur through hypermethylation of the CpG
      island promoter of MST1, MST2 and/or RASSF1A in human sarcomas.

PMID- 17538947
TI  - Retinoids and skin: microarrays shed new light on chemopreventive action of all
      trans retinoic acid.
AB  - Despite the use of retinoids in the clinic for many years, their mode of action
      in the prevention of skin cancer is still unclear. Recent microarray analyses of
      the chemopreventive effect of all-trans retinoic acid (ATRA), one of the primary
      naturally occurring biologically active retinoids, in the two-stage mouse skin
      chemical carcinogenesis model have provided novel insight into their action.
      Comparison of the gene expression profiles of control skin to skin subjected to
      the two-stage protocol for 3 wk, with or without ATRA, has shown that
      approximately half of the genes regulated by 12-o-tetradecanoylphorbol-13-acetate
      (TPA) are oppositely regulated when ATRA is coadministered with TPA. It was
      further shown the Raf/Mek/Erk branch of mitogen-activated protein (MAP) kinase
      pathway contains a disproportionate number of oppositely regulated genes, thereby
      implicating it as one of the key pathways involved in tumor promotion by TPA,
      that is blocked by ATRA. This result has pointed the way toward the detailed
      study of Raf/Mek/Erk pathway signaling in skin cancer development and its
      potential as a target pathway for chemoprevention by ATRA and other
      chemopreventive drugs.

PMID- 17538948
TI  - Buck (Capra hircus) genes encode new members of the spermadhesin family.
AB  - Spermadhesins are the major proteins of boar seminal plasma and form a group of
      polypeptides probably involved in reproduction. In previous work, a member of the
      spermadhesin family from buck seminal plasma, called BSFP, was characterized by
      mass spectrometry and N-terminal sequencing. The present study aimed to clone and
      characterize the BSFP gene and investigate its expression along the genital tract
      using real-time polymerase chain reaction (PCR). The cDNAs of the seminal
      vesicle, testis, epididymis, bulbourethral gland, and ductus deferens were
      prepared from a buck. Following 3'- and 5'-end amplifications using seminal
      vesicle cDNA, we cloned and sequenced four highly similar (97-98%) nucleotide
      sequences encoding spermadhesins, which were named Bodhesin-1(Bdh-1), Bdh-2, Bdh
      3, and Bdh-4. All deduced amino acid sequences contained the CUB domain signature
      and were 49-52% similar to boar AWN. Among the four Bdh amino acid sequences, Bdh
      2 was the most similar to the BSFP N-terminal fragment. By using real-time PCR,
      it was verified specific amplifications for all Bdh in the seminal vesicle,
      testis, epididymis, and bulbourethral gland, with the exception of Bdh-2 in
      epididymis. The amplicons had a melting temperature and size of approximately 78
      degrees C and 130 bp, respectively. Bdh expression was higher in the seminal
      vesicle when compared to the other tissues. The present work confirms that goat
      is the fifth mammalian species, after pig, cattle, horse, and sheep, in which
      spermadhesin molecules are found. To the best of our knowledge, this is the first
      report on buck spermadhesin genes using molecular cloning and expression profile.

PMID- 17538949
TI  - Comparison of acid mucin goblet cell distribution and Hox13 expression patterns
      in the developing vertebrate digestive tract.
AB  - The digestive tract of vertebrates is a complex organ system required for the
      digestion of food and the absorption of nutrients. The colon evolved as a water
      absorption organ essential for vertebrates to survive on land. In contrast to
      land vertebrates, the Chondrichthyes (sharks, skates and rays) are nearly iso
      osmotic with their ocean environment and do not reabsorb water from food waste.
      To understand the origin of the vertebrate colon, we examined the distribution of
      sulfated and sialyated mucus-producing cells in the little skate, Raja erinacea,
      as an indication of water absorption function in the chondrichthian digestive
      tract. The percentage of acid mucin producing goblet cells was analyzed in the
      spiral valve and hindgut of little skate and the small intestine and colon of
      mouse embryos. Levels of acid mucins in the hindgut of the little skate was
      comparable to that of the small intestines of terrestrial vertebrates, whereas
      the distal region of the spiral valve contained high levels of acid mucin
      producing cells similar to the colon of mouse and chick. The low numbers of acid
      mucins in the little skate hindgut confirms that a functional colon for water
      absorption is absent in the Chondrichthyes. Interestingly, the presence of high
      levels of acid mucins in the posterior spiral valve provides evidence for a
      possible primordial water-absorbing organ in the elasmobranchs. Hoxd13 patterns
      acid mucins in the colons of terrestrial vertebrates. Expression of Hoxd13 and
      Hoxa13 in R. erinacea suggests conserved roles for Hox genes in patterning the
      early hindgut.

PMID- 17538950
TI  - Group analysis and the subject factor in functional magnetic resonance imaging:
      analysis of fifty right-handed healthy subjects in a semantic language task.
AB  - Before considering a given fMRI paradigm as a valid clinical tool, one should
      first assess the reliability of functional responses across subjects by
      establishing a normative database and defining a reference activation map that
      identifies major brain regions involved in the task at hand. However, the
      definition of such a reference map can be hindered by inter-individual functional
      variability. In this study, we analysed functional data obtained from 50 healthy
      subjects during a semantic language task to assess the influence of the number of
      subjects on the reference map and to characterise inter-individual functional
      variability. We first compared different group analysis approaches and showed
      that the extent of the activated network depends not only on the choice of the
      analysis approach but also on the statistical threshold used and the number of
      subjects included. This analysis suggested that, while the RFX analysis is
      suitable to detect confidently true positive activations, the other group
      approaches are useful for exploratory investigations in small samples. The
      application of quantitative measures at the voxel and regional levels suggested
      that while approximately 15-20 subjects were sufficient to reveal reliable and
      robust left hemisphere activations, >30 subjects were necessary for revealing
      more variable and weak right hemisphere ones. Finally, to visualise inter
      individual variability, we combined two similarity indices that assess the
      percentages of true positive and false negative voxels in individual activation
      patterns relative to the group map. We suggest that these measures can be used
      for the estimation of the degree of 'normality' of functional responses in brain
      damaged patients, where this question is often raised, and recommend the use of
      different quantifications to appreciate accurately the inter-individual
      functional variability that can be incorporated in group maps.

PMID- 17538951
TI  - Linear age-correlated functional development of right inferior fronto-striato
      cerebellar networks during response inhibition and anterior cingulate during
      error-related processes.
AB  - Inhibitory and performance-monitoring functions have been shown to develop
      throughout adolescence. The developmental functional magnetic resonance imaging
      (fMRI) literature on inhibitory control, however, has been relatively
      inconsistent with respect to functional development of prefrontal cortex in the
      progression from childhood to adulthood. Age-related performance differences
      between adults and children have been shown to be a confound and may explain
      inconsistencies in findings. The development of error-related processes has not
      been studied so far using fMRI. The aim of this study was to investigate the
      neural substrates of the development of inhibitory control and error-related
      functions by use of an individually adjusted task design that forced subjects to
      fail on 50% of trials, and therefore controlled for differences in task
      difficulty and performance between different age groups. Event-related fMRI was
      used to compare brain activation between 21 adults and 26 children/adolescents
      during successful motor inhibition and inhibition failure. Adults compared with
      children/adolescents showed increased brain activation in right inferior
      prefrontal cortex during successful inhibition and in anterior cingulate during
      inhibition failure. A whole-brain age-regression analysis between 10 and 42 years
      showed progressive age-related changes in activation in these two brain regions,
      with additional changes in thalamus, striatum, and cerebellum. Age-correlated
      brain regions correlated with each other and with inhibitory performance,
      suggesting they form developing fronto-striato-thalamic and fronto-cerebellar
      neural pathways for inhibitory control. This study shows developmental
      specialization of the integrated function of right inferior prefrontal cortex,
      basal ganglia, thalamus, and cerebellum for inhibitory control and of anterior
      cingulate gyrus for error-related processes.

PMID- 17538952
TI  - Functional cortical changes of the sensorimotor network are associated with
      clinical recovery in multiple sclerosis.
AB  - OBJECTIVE: To assess the early cortical changes following an acute motor relapse
      secondary to a pseudotumoral lesion in MS patients, the longitudinal cortical
      functional correlates of clinical recovery, and the evolution over time of
      cortical reorganization. METHODS: FMRI during the performance of a simple motor
      task were obtained from 12 MS patients (after a clinical attack involving the
      motor system secondary to a pseudotumoral lesion) and 15 matched controls. In six
      patients and five controls, a longitudinal fMRI study was also performed.
      RESULTS: In patients, at baseline, the primary sensorimotor cortex (SMC) of the
      ipsilateral (contralesional) hemisphere was significantly more active during task
      performance with the impaired than the unimpaired hand. During task performance
      with the unimpaired hand, the ipsilateral cerebellum and several motor areas in
      the contralateral hemisphere were significantly more active. Pseudotumoral lesion
      volume was correlated with activation of the primary SMC bilaterally (r = -0.86
      and -0.85) and the nine-hole peg test score with activation of the primary SMC of
      the affected hemisphere (r = 0.88). A recovery of function of the primary SMC of
      the affected hemisphere was found in the four patients with clinical improvement.
      In the two patients without clinical recovery, there was a persistent recruitment
      of the primary SMC of the unaffected hemisphere. CONCLUSIONS: Pseudotumoral MS
      lesions affecting the motor system can determine short-term cortical changes
      characterized by the recruitment of pathways in the unaffected hemisphere. The
      regain of function of motor areas of the affected hemisphere seems to be a
      critical factor for a favorable recovery.

PMID- 17538953
TI  - Possible cross-regulation of the E prostanoid receptors.
AB  - Exposure to UVB induces an inflammatory response in the skin that results in high
      levels of cyclooxygenase-2 (COX-2) and its enzymatic product, prostaglandin E2
      (PGE(2)). PGE(2) signals via one of four E prostanoid (EP) receptors, EP1-4, but
      the roles of each of these receptors in UVB-mediated inflammation and skin
      carcinogenesis have not been fully defined. Topical application of ONO-8713, an
      EP1 antagonist, reduced the acute inflammatory effects of UVB irradiation. This
      compound also reduced UVB-induced tumor formation by approximately 50%,
      suggesting that signaling of PGE(2) via the EP1 receptor may play a role in UVB
      mediated inflammation and carcinogenesis. Our laboratory has demonstrated that
      the EP1 receptor localized to the suprabasal layers of the epidermis and the EP3
      receptor was found in the basal keratinocytes of unirradiated murine skin. While
      UVB exposure induced no change in the localization of the EP1 receptor, the EP3
      receptor was detected in all layers of the epidermis in response to UVB. In mice
      that were topically treated with ONO-8713, UVB-induced changes in EP3
      localization were prevented. This alteration in EP3 receptor localization was not
      seen following topical application of the anti-inflammatory drug celecoxib,
      indicating that the effects of ONO-8713 were not because of its anti-inflammatory
      properties. These results suggest a previously undescribed interaction between
      the EP1 and EP3 receptors in the epidermis.

PMID- 17538954
TI  - Intrinsic resistance to apoptosis of colon epithelial cells is a potential
      determining factor in the susceptibility of the A/J mouse strain to
      dimethylhydrazine-induced colon tumorigenesis.
AB  - Alterations in the delicate balance between cell proliferation and cell death
      disrupt colon homeostasis and serve as determining factors in colon
      tumorigenesis. The two mouse strains, AKR/J (resistant) and A/J (susceptible),
      have been widely used as models for dimethylhydrazine-induced colon
      tumorigenesis. This study examined whether the differential susceptibilities of
      the two mouse strains to the tumorigenic effect of dimethylhydrazine were
      associated with intrinsic differences in the apoptotic machinery of the colon
      epithelial cells. While acute exposure to dimethylhydrazine caused massive
      apoptosis of colon epithelial cells in AKR/J mice, the effect was considerably
      less in A/J mice. Apoptosis in AKR/J mice occurred not only in the luminal side
      of the mucosa but also deep in the colonic crypts. In addition, this apoptosis
      appeared to involve caspase-3. The increased sensitivity of AKR/J to
      dimethylhydrazine was associated with a persistent expression of tumor necrosis
      factor (TNF) but not of its receptors. After establishing a new method for
      isolating primary colon epithelial cells, we determined that cells derived from
      A/J mice were substantially more resistant to apoptosis in response to
      dimethylhydrazine or to a combination of TNF, cyclohexamide, and butyrate
      compared to cells from AKR/J mice. These results strongly suggest that a higher
      intrinsic resistance to apoptosis of colon epithelial cells may be an important
      determinant of predisposition to colon tumorigenesis in the A/J mouse strain.

PMID- 17538955
TI  - The functional contrariety of JNK.
AB  - The JNK proteins are activated by multiple and diverse stimuli, leading to varied
      and seemingly contradictory cellular responses. In particular, JNKs have been
      reported to have a role in the induction of apoptosis, but have also been
      implicated in enhancing cell survival and proliferation. Thus the JNK proteins
      seem to represent an archetype of contrariety of intracellular signaling. The
      opposing roles of JNKs have been attributed to the observation that JNKs activate
      different substrates based on specific stimulus, cell type or temporal aspects.
      Because of their analogous expression in apparently almost every tissue, JNK1 and
      JNK2 have most often been considered to have overlapping or redundant functions.
      In spite of this assessment, research evidence suggests that the functions of
      JNKs should be addressed in a manner that differentiates between their precise
      contributions. Specifically in this review, we examine evidence regarding whether
      the JNKs proteins might play distinctive roles in cellular processes associated
      with carcinogenesis.

PMID- 17538956
TI  - The mechanisms of tumor suppressor effect of glucocorticoid receptor in skin.
AB  - Glucocorticoid hormones exert a tumor suppressor effect in different experimental
      models, including mouse skin carcinogenesis. The glucocorticoid control of
      cellular functions is mediated via the glucocorticoid receptor (GR), a well-known
      transcription factor that regulates genes by DNA-binding dependent
      transactivation, and DNA-binding independent transrepression through negative
      interaction with other transcription factors. In this perspective, we analyze
      known mechanisms that underlie the anticancer effect of GR signaling, including
      effects on cell growth, differentiation, apoptosis, and angiogenesis. We also
      discuss a novel mechanism for the tumor suppressor effect of the GR in skin:
      through the regulation of the number and status of follicular epithelial stem
      cells (SC), which are a target cell population for skin carcinogenesis. Our
      studies on keratin5.GR transgenic animals that are resistant to skin
      carcinogenesis, demonstrated that the GR diminishes the number of follicular
      epithelial SCs, reduces their proliferative and survival potential and affects
      the expression of follicular SC "signature" genes. The analysis of global effect
      of the GR on gene expression in follicular epithelial SCs, basal keratinocytes,
      and mouse skin tumors provided an unexpected evidence that gene transrepression
      by GR plays an important role in the maintenance of SC and in inhibition of skin
      carcinogenesis by this steroid hormone receptor. It is known that
      antiinflammatory effect of glucocorticoids is chiefly mediated by GR
      transrepression. Thus, our findings suggest the similarity between the mechanisms
      of antiinflammatory and anticancer effects of the GR signaling. We discuss the
      potential clinical applications of our findings in light of drug discovery
      programs focused on the development of selective GR modulators that
      preferentially induce GR transrepression.

PMID- 17538957
TI  - Changes in cathepsin gene expression and relative enzymatic activity during
      gilthead sea bream oogenesis.
AB  - The aim of this study was to provide evidence on the modulation of lysosomal
      enzymes in terms of both gene expression and enzymatic activity during follicle
      maturation. For this purpose three lysosomal enzymes, cathepsins B, D, and L,
      were studied in relation to yolk formation and degradation, during the main
      phases of ovarian follicle growth in the pelagophil species, the sea bream Sparus
      aurata. Specific attention was focused on the gene expression quantification
      method, on the assay of enzymatic activities, and on the relationship between the
      proteolytic cleavage of yolk proteins (YPs), cathepsin gene expression and
      cathepsin activities. For the gene expression study, the cathepsins B-like and L
      like mRNAs were isolated and partially or fully characterized, respectively; the
      sequences were used as design specific primers for the quantification of
      cathepsin gene expression by real-time PCR, in follicles at different stages of
      maturation. The enzymatic assays for cathepsins B, D, and L were optimized in
      terms of specificity, sensitivity and reliability, using specific substrates and
      inhibitors. In ovulated eggs, the lipovitellin I (LV I) was degraded and the
      changes in electrophoretic pattern were preceded by an increase in the activity
      of a cysteine proteinase, cathepsin L, and its mRNA. Cathepsin B did not appear
      to be involved in YP changes during the final maturation stage.

PMID- 17538958
TI  - Towards a ZP-based contraceptive for marsupials: comparative analysis and
      developmental expression of marsupial ZP genes.
AB  - Fertility control in the form of a zona pellucida (ZP)-based immunocontraceptive
      has shown potential as a humane form of control for overabundant marsupials
      including the brushtail possum and macropods. Further refinement and development
      of a ZP-based vaccine requires detailed knowledge of the protein structure and
      expression in order to ensure maximum efficacy and specificity. Sequencing and
      comparative analysis of the ZP3 protein from three marsupial orders in this study
      found a high overall level of conservation; within order Diprotodontia, the ZP3
      protein is 86.9-98.9% identical. ZP3 identity falls to 56.6-57.2%, when the grey,
      short-tailed opossum (a Didelphimorphian) is compared to dasyurid and
      diprotodontan marsupials. This is similar to its amino acid identity with ZP3
      from eutherian species (50.7-52.8%). Comparison of a 21 amino acid epitope in
      marsupial ZP3 that has shown contraceptive effects, reveals 95-100% identity
      between the four macropodid species, 81-86% amino acid identity between brushtail
      possum and the macropods and 67-71% identity between the diprotodontans and the
      fat-tailed dunnart (a dasyurid). This is comparable to the level of identity
      between related eutherian mammals. The expression pattern of three ZP genes
      during brushtail possum and tammar wallaby pouch young development was examined
      by RT-PCR. This analysis of ZP gene expression has confirmed that ZP mRNA
      transcription begins in the ovary during pouch young development by about 51 days
      of age. The presence of ZP transcripts at this stage in pouch young development
      suggests that marsupial ZP gene transcription begins before the onset of
      follicular development.

PMID- 17538959
TI  - The composition of milk from Bolivian squirrel monkeys (Saimiri boliviensis
      boliviensis).
AB  - Squirrel monkeys (genus Saimiri) give birth to relatively large neonates with
      large, fast-growing brains. Maternal energy expenditure during gestation and
      infant development is argued to be high, but may be offset by the provisioning of
      offspring by females other than the mother (allonursing). Milk composition is an
      important component of maternal energy expenditure, but has been examined in only
      a small number of primate species. Here, we report on the milk composition from
      laboratory-housed Bolivian squirrel monkey (Saimiri boliviensis boliviensis) dams
      (n = 6) and allomothers (n = 2). Milk samples (n = 16) representing mid-lactation
      were assayed for fat, sugar, dry matter (DM), crude protein (CP), and fatty
      acids. Gross energy (GE) was calculated from these constituents (excepting fatty
      acids). The goals of this project were: (1) to provide descriptive data on milk
      composition of squirrel monkeys, including the range of intraspecific variation;
      (2) to determine if milk produced by allomothers differs from milk from dams; and
      (3) to compare squirrel monkey milk to that of other small New World monkeys, the
      callitrichines. Squirrel monkey samples averaged 4.56% fat, 3.59% CP, 6.98%
      sugar, 16.59% DM, and 0.91 kcal/g. The proportion of the medium chain fatty acids
      8:0 and 10:0 was 40 times greater than that reported for human milk samples, and
      18:1 and 18:2n-6 comprise more than 60% of total fatty acids. Milk from
      allomothers was lower than dams in fat, DM, and GE, which may relate to variation
      in maternal condition between these two groups. Excluding allomothers, milk from
      squirrel monkeys was higher in mean GE than captive common marmosets, but did not
      differ in the proportion of energy from fat, CP, and sugar relative to total GE.
      The consistency in energy from protein between species suggests this may be a
      shared-derived trait of New World monkeys.

PMID- 17538960
TI  - The AASLD and public policy: coming in out of the cold.

PMID- 17538961
TI  - Advocacy: what is a nice scientist like you doing in Washington, DC?

PMID- 17538962
TI  - Therapy for hepatocyte transporter trafficking mutations: the time is now.

PMID- 17538963
TI  - Good fat/bad fat.

PMID- 17538964
TI  - Engulfment of apoptotic cells expressing HCV proteins leads to differential
      chemokine expression and STAT signaling in human dendritic cells.
AB  - In the majority of cases, infection with hepatitis C virus (HCV) becomes chronic
      and is often associated with impaired innate and adaptive immune responses. The
      mechanisms underlying viral persistence and lack of protective immunity are
      poorly understood. Considering that dendritic cells (DCs) play critical roles in
      initiating and modulating immune responses, we explored the effect of HCV
      proteins on DC gene and protein expression, phenotype, and function. Human DCs
      were generated following plastic adherence of monocytes and culture with
      granulocyte-macrophage colony-stimulating factor and interleukin-4 (IL-4) from
      normal subjects. Autologous nonadherent peripheral blood mononuclear cells were
      infected with vaccinia constructs expressing various HCV proteins (core-E1, NS5A,
      NS5B) or an irrelevant protein beta-galactosidase (beta-gal) as the control,
      induced to undergo apoptosis, then co-cultured with DCs. Between 2% and 10% of
      the genes probed in a cDNA nylon array were differentially regulated within DCs
      that had engulfed HCV proteins. In particular, the presence of intracellular NS5A
      led to increased transcriptional and protein expression of IL-8 (CXCL-8), a
      chemokine with proinflammatory and anti-interferon properties, and impaired
      interferon induction of signal transducers and activators of transcription 1
      (STAT1) serine and tyrosine and STAT2 tyrosine phosphorylation. CONCLUSION: These
      data provide novel mechanisms by which HCV subverts antiviral host immunity.

PMID- 17538965
TI  - Ethanol and fish oil induce NFkappaB transactivation of the collagen alpha2(I)
      promoter through lipid peroxidation-driven activation of the PKC-PI3K-Akt
      pathway.
AB  - To analyze whether fish oil, as a source of polyunsaturated fatty acids from the
      n-3 series, could synergize with ethanol to promote collagen I upregulation in
      vivo, collagen alpha2(I) promoter-betaGal (COL1A2-betaGal) transgenic mice were
      fed a diet enriched in fish oil in the presence of ethanol (ethanol group) or
      dextrose (control group). Ethanol-fed mice showed mild steatosis, increased
      alanine aminotransferase (ALT), aspartate aminotransferase (AST), nonsterified
      fatty acids, and plasma alcohol levels along with elevated cytochrome P450 2E1
      activity, lipid peroxidation end products, and low glutathione (GSH) levels,
      which suggested enhanced oxidant stress and liver injury. Increased
      transactivation of the COL1A2 promoter assessed by betaGal activity was shown in
      vivo and by transfection with deletion constructs for the collagen alpha1(I)
      promoter (COL1A1) and COL1A2 promoters in vitro. Transcriptional regulation of
      both COL1A1 and COL1A2 promoters was validated by nuclear in vitro transcription
      run-on, northern blot analysis, and quantitative polymerase chain reaction, which
      was followed by the subsequent upregulation of collagen I protein with no changes
      in matrix metalloproteinase 13 (MMP 13). To further analyze the potential
      mechanism for collagen I upregulation, an in vitro coculture model was designed
      with primary stellate cells seeded on the bottom plate of a Boyden chamber and
      the rest of the liver cells plated on a cell culture insert, and fish oil or fish
      oil plus ethanol were added. The combination of fish oil plus ethanol increased
      nuclear factor kappaB binding to the COL1A2 promoter both in vivo and in the
      cocultures and also resulted in increased phosphorylation of protein kinase C,
      activation of PI3 kinase, and phosphorylation of Akt. The in vitro addition of
      vitamin E prevented such activation and collagen I increase. Furthermore,
      inhibitors of all 3 kinases blocked the increase in collagen I and NFkappaB
      binding to the COL1A2 promoter; the latter was also prevented by vitamin E.
      CONCLUSION: These results suggest that fish oil (mainly n-3 polyunsaturated fatty
      acids [PUFAs]) can synergize with ethanol to induce collagen I, transactivating
      the COL1A2 promoter through a lipid peroxidation-PKC-PI3K-Akt-NFkappaB-driven
      mechanism in the absence of overt steatosis and inflammation.

PMID- 17538966
TI  - Remarkable heterogeneity displayed by oval cells in rat and mouse models of stem
      cell-mediated liver regeneration.
AB  - The experimental protocols used in the investigation of stem cell-mediated liver
      regeneration in rodents are characterized by activation of the hepatic stem cell
      compartment in the canals of Hering followed by transit amplification of oval
      cells and their subsequent differentiation along hepatic lineages. Although the
      protocols are numerous and often used interchangeably across species, a thorough
      comparative phenotypic analysis of oval cells in rats and mice using well
      established and generally acknowledged molecular markers has not been provided.
      In the present study, we evaluated and compared the molecular phenotypes of oval
      cells in several of the most commonly used protocols of stem cell-mediated liver
      regeneration-namely, treatment with 2-acetylaminofluorene and partial (70%)
      hepatectomy (AAF/PHx); a choline-deficient, ethionine-supplemented (CDE) diet; a
      3,5-diethoxycarbonyl-1,4-dihydro-collidin (DDC) diet; and N-acetyl-paraaminophen
      (APAP). Reproducibly, oval cells showing reactivity for cytokeratins (CKs),
      muscle pyruvate kinase (MPK), the adenosine triphosphate-binding cassette
      transporter ABCG2/BCRP1 (ABCG2), alpha-fetoprotein (AFP), and delta-like protein
      1/preadipocyte factor 1 (Dlk/Pref-1) were induced in rat liver treated according
      to the AAF/PHx and CDE but not the DDC protocol. In mouse liver, the CDE, DDC,
      and APAP protocols all induced CKs and ABCG2-positive oval cells. However, AFP
      and Dlk/Pref-1 expression was rarely detected in oval cells. CONCLUSION: Our
      results delineate remarkable phenotypic discrepancies exhibited by oval cells in
      stem cell-mediated liver regeneration between rats and mice and underline the
      importance of careful extrapolation between individual species.

PMID- 17538967
TI  - Glucocorticoid signaling synchronizes the liver circadian transcriptome.
AB  - Circadian control of physiology is mediated by local, tissue-based clocks,
      synchronized to each other and to solar time by signals from the suprachiasmatic
      nuclei (SCN), the master oscillator in the hypothalamus. These local clocks
      coordinate the transcription of key pathways to establish tissue-specific daily
      metabolic programs. How local transcriptomes are synchronized across the organism
      and their relative contribution to circadian output remain unclear. In the
      present study we showed that glucocorticoids alone are able to synchronize
      expression of about 60% of the circadian transcriptome. We propose that
      synchronization occurs directly by the action of glucocorticoids on a diverse
      range of downstream targets and indirectly by regulating the core clock genes
      mPer1, Bmal1, mCry1, and Dbp. We have identified the pivotal liver transcription
      factor, HNF4alpha, as a mediator of circadian and glucocorticoid-regulated
      transcription, showing that it is a key conduit for downstream targeting.
      CONCLUSION: We have demonstrated that by orchestrating transcriptional cascades,
      glucocorticoids are able to direct synchronization of a diverse range of
      functionally important circadian genes.

PMID- 17538969
TI  - Population prevalence and symptom associations of autonomic dysfunction in
      primary biliary cirrhosis.
AB  - Patients with primary biliary cirrhosis (PBC) frequently experience significant
      fatigue thought to result from as-yet-unidentified central nervous system (CNS)
      mediated processes. Pilot studies have suggested that autonomic dysfunction is a
      frequent occurrence in PBC and may contribute to the pathogenesis of this
      fatigue. The degree to which autonomic dysfunction affects the PBC population as
      a whole, and its interrelationship with other symptoms experienced by PBC
      patients remains unstudied. In this study, we used a geographically defined,
      fully representative PBC patient cohort to study the prevalence of symptoms of
      autonomic dysfunction and its relationship with other symptoms of PBC. Symptoms
      of cardiovascular autonomic dysfunction (as assessed using the Orthostatic
      Grading Scale [OGS]) were significantly more frequently reported and
      significantly more severe in PBC patients than in both matched normal controls
      (40% versus 6% with moderate or worse orthostasis (P < .0001), mean OGS score 3.2
      +/- 3.4 versus 1.3 +/- 1.9, P < .005) and in patients with primary sclerosing
      cholangitis and in severity were independently associated with severity of
      fatigue and cognitive symptoms (both r2 = 0.3, P < .0001). Thirteen of 20
      patients with an OGS value > 4 (moderate severity and worse) had significant
      abnormality in autonomic regulation of blood pressure, which was identified on
      dynamic testing. CONCLUSION: Symptoms suggestive of autonomic dysfunction
      frequently occur in PBC patients and reflect dysregulation of actual blood
      pressure. Autonomic dysfunction is independently associated with both fatigue
      and, importantly, symptoms of cognitive dysfunction, suggesting the potential for
      significant organic sequelae.

PMID- 17538968
TI  - Elevated troponin I levels in acute liver failure: is myocardial injury an
      integral part of acute liver failure?
AB  - Although rare instances of cardiac injury or arrhythmias have been reported in
      acute liver failure (ALF), overall, the heart is considered to be spared in this
      condition. Troponin I, a sensitive and specific marker of myocardial injury, may
      be elevated in patients with sepsis and acute stroke without underlying acute
      coronary syndrome, indicating unrecognized cardiac injury in these settings. We
      sought to determine whether subclinical cardiac injury might also occur in acute
      liver failure. Serum troponin I levels were measured in 187 patients enrolled in
      the US Acute Liver Failure Study Group registry, and correlated with clinical
      variables and outcomes. Diagnoses were representative of the larger group of
      >1000 patients thus far enrolled and included 80 with acetaminophen-related
      injury, 26 with viral hepatitis, 19 with ischemic injury, and 62 others. Overall,
      74% of patients had elevated troponin I levels (>0.1 ng/ml). Patients with
      elevated troponin I levels were more likely to have advanced hepatic coma (grades
      III or IV) or to die (for troponin I levels >0.1 ng/ml, odds ratio 3.88 and 4.69
      for advanced coma or death, respectively). CONCLUSION: In acute liver failure,
      subclinical myocardial injury appears to occur more commonly than has been
      recognized, and its pathogenesis in the context of acute liver failure is
      unclear. Elevated troponin levels are associated with a significant increase in
      morbidity and mortality. Measurement of troponin I levels may be helpful in
      patients with acute liver failure, to detect unrecognized myocardial damage and
      as a marker of unfavorable outcome.

PMID- 17538970
TI  - Induction of cytochrome P450 2E1 [corrected] promotes liver injury in ob/ob mice.
AB  - Cytochrome P450 2E1 (CYP2E1) activates several hepatotoxins and contributes to
      alcoholic liver damage. Obesity is a growing health problem in the United States.
      The aim of the present study was to evaluate whether acetone- or pyrazole
      mediated induction of CYP2E1 can potentiate liver injury in obesity. CYP2E1
      protein and activity were elevated in acetone- or pyrazole-treated obese and lean
      mice. Acetone or pyrazole induced distinct histological changes in liver and
      significantly higher aminotransferase enzymes in obese mice compared to obese
      controls or acetone- or pyrazole-treated lean mice. Higher caspase-3 activity and
      numerous apoptotic hepatocytes were observed in the acetone- or pyrazole-treated
      obese mice. Increased protein carbonyls, malondialdehyde, 4-hydroxynonenal
      protein adducts, elevated levels of inducible nitric oxide synthase, and higher 3
      nitrotyrosine protein adducts were found in livers of acetone- or pyrazole
      treated obese animals, suggesting elevated oxidative and nitrosative stress.
      Liver tumor necrosis factor alpha levels were higher in pyrazole-treated animals.
      The CYP2E1 inhibitor chlormethiazole and iNOS inhibitor N-(3-(aminomethyl)
      benzyl) acetamidine abrogated the toxicity and the oxidative/nitrosative stress
      elicited by the induction of CYP2E1. CONCLUSION: These results show that obesity
      contributes to oxidative stress and liver injury and that induction of CYP2E1
      enhances these effects.

PMID- 17538971
TI  - The female genital morphology of the orb weaving spider genus Agriognatha
      (Araneae, Tetragnathidae).
AB  - The female genital morphology of the spiders in the araneoid genus Agriognatha
      (Tetragnathidae) is described and illustrated. The female genitalia of
      Agriognatha is characterized by a strong reduction of the sperm storage organs
      (spermathecae) and by the presence of a specialized distal compartment of the
      median membranous chamber that functions as a sperm storage organ (the posterior
      sac). The genital morphology of Agriognatha species is unique among
      Tetragnathidae and it provides robust synapomorphic evidence for the monophyly of
      genus. We discuss the phylogenetic implications of these new findings for the
      placement and monophyly of Agriognatha and for the monophyly of Tetragnathinae.

PMID- 17538972
TI  - Cranial ontogeny in Philautus silus (Anura: Ranidae: Rhacophorinae) reveals few
      similarities with other direct-developing anurans.
AB  - Direct development has evolved in rhacophorine frogs independently from other
      anuran lineages, thereby offering an opportunity to assess features associated
      with this derived life history. Using a developmental series of the direct
      developing Philautus silus (Ranidae: Rhacophorinae) from Sri Lanka, we examine
      features of cranial morphology that are part of a suite of adaptations that
      facilitate feeding in free-living tadpoles, but have been changed or lost in
      other direct-developing lineages. Larval-specific upper jaw cartilages, which are
      absent from many non-rhacophorine direct-developing species (such as
      Eleutherodactylus coqui), develop in embryos of P. silus. Similarly, lower jaw
      cartilages initially assume a larval morphology, which is subsequently remodeled
      into the adult jaw configuration before hatching. However, the cartilaginous jaw
      suspension and hyobranchial skeleton never assume a typical larval morphology.
      The palatoquadrate, which suspends the lower jaw, lacks the posterior connections
      to the braincase found in many metamorphosing species. Unlike in metamorphosing
      species, bone formation in P. silus begins before hatching. However, the sequence
      of bone formation resembles that of metamorphosing anurans more than that of
      other direct developers. In particular, P. silus does not exhibit precocious
      ossification of the lower jaw, which is characteristic of some frogs and
      caecilians that lack a free-living tadpole. These data reveal some similarities
      between Philautus and other direct-developing anurans. However, the departure of
      Philautus embryos from the generalized tadpole skeletal morphology is less
      pronounced than that observed in other direct-developing taxa.

PMID- 17538973
TI  - Deer antler regeneration: cells, concepts, and controversies.
AB  - The periodic replacement of antlers is an exceptional regenerative process in
      mammals, which in general are unable to regenerate complete body appendages.
      Antler regeneration has traditionally been viewed as an epimorphic process
      closely resembling limb regeneration in urodele amphibians, and the terminology
      of the latter process has also been applied to antler regeneration. More recent
      studies, however, showed that, unlike urodele limb regeneration, antler
      regeneration does not involve cell dedifferentiation and the formation of a
      blastema from these dedifferentiated cells. Rather, these studies suggest that
      antler regeneration is a stem-cell-based process that depends on the periodic
      activation of, presumably neural-crest-derived, periosteal stem cells of the
      distal pedicle. The evidence for this hypothesis is reviewed and as a result, a
      new concept of antler regeneration as a process of stem-cell-based epimorphic
      regeneration is proposed that does not involve cell dedifferentiation or
      transdifferentiation. Antler regeneration illustrates that extensive appendage
      regeneration in a postnatal mammal can be achieved by a developmental process
      that differs in several fundamental aspects from limb regeneration in urodeles.

PMID- 17538974
TI  - Comparing smoothing techniques in Cox models for exposure-response relationships.
AB  - To allow for non-linear exposure-response relationships, we applied flexible non
      parametric smoothing techniques to models of time to lung cancer mortality in two
      occupational cohorts with skewed exposure distributions. We focused on three
      different smoothing techniques in Cox models: penalized splines, restricted cubic
      splines, and fractional polynomials. We compared standard software
      implementations of these three methods based on their visual representation and
      criterion for model selection. We propose a measure of the difference between a
      pair of curves based on the area between them, standardized by the average of the
      areas under the pair of curves. To capture the variation in the difference over
      the range of exposure, the area between curves was also calculated at percentiles
      of exposure and expressed as a percentage of the total difference. The dose
      response curves from the three methods were similar in both studies over the
      denser portion of the exposure range, with the difference between curves up to
      the 50th percentile less than 1 per cent of the total difference. A comparison of
      inverse variance weighted areas applied to the data set with a more skewed
      exposure distribution allowed us to estimate area differences with more precision
      by reducing the proportion attributed to the upper 1 per cent tail region.
      Overall, the penalized spline and the restricted cubic spline were closer to each
      other than either was to the fractional polynomial.

PMID- 17538975
TI  - Induction chemotherapy selects patients with locally advanced, unresectable
      pancreatic cancer for optimal benefit from consolidative chemoradiation therapy.
AB  - BACKGROUND: The current study was conducted to determine whether there were
      differences in outcome for patients with unresectable locally advanced pancreatic
      cancer (LAPC) who received treatment with chemoradiation therapy (CR) versus
      induction chemotherapy followed by CR (CCR). METHODS: Between December 1993 and
      July 2005, 323 consecutive patients with LAPC were treated at the authors'
      institution with radiotherapy and concurrent gemcitabine or fluoropyrimidine
      chemotherapy. Two hundred forty-seven patients received CR as initial treatment,
      and 76 patients received a median of 2.5 months of gemcitabine-based induction
      chemotherapy prior to CR. Most patients received a radiation dose of 30 grays in
      10 fractions (85%) concurrently with infusional 5-fluorouracil (41%), gemcitabine
      (39%), or capecitabine (20%). RESULTS: The median follow-up was 5.5 months
      (range, 1-63 months). For all patients, the median overall survival (OS) and
      progression-free survival (PFS) were 9 months and 5 months, respectively, and the
      2-year estimated OS and PFS rates were 9% and 5%, respectively. The median OS and
      PFS were 8.5 months and 4.2 months, respectively, in the CR group and 11.9 months
      and 6.4 months, respectively, in the CCR group (both P < .001). The median times
      to local and distant progression were 6.0 months and 5.6 months, respectively, in
      the CR group and 8.9 and 9.5 months, respectively, in the CCR group (P = .003 and
      P = .007, respectively). There was no significant difference in the patterns of
      failure with the use of induction chemotherapy. CONCLUSIONS: The results from
      this analysis indicated that, by excluding patients with rapid distant
      progression, induction chemotherapy may select patients with LAPC for optimal
      benefit from consolidative CR. The authors believe that this strategy of
      enriching the population of patients who receive a locoregional treatment
      modality merits prospective randomized evaluation.

PMID- 17538977
TI  - Laser desorption/ionization determination of molecular weight distributions of
      polyaromatic carbonaceous compounds and their aggregates.
AB  - Molecular weight distributions (MWDs) of model polyaromatic hydrocarbons (PAHs)
      and complex asphaltene samples have been investigated in laser
      desorption/ionization mass spectrometry (LDI-MS) experiments. Special efforts are
      devoted to the characterization of aggregation effects during the desorption
      process. It is found that non-covalent clusters of the PAHs and asphaltenes form
      readily in the desorbing plume. Aggregation is favoured in the experiments
      performed on dense samples at high laser energy and under continuous ion
      extraction conditions. In the absence of polar groups in the analyte molecules,
      the aggregation propensity correlates well with the size of the polycondensed
      system and with its degree of pericondensation, in qualitative agreement with
      previous theoretical predictions. For the polydispersed asphaltenes from two
      different crude oils, MWDs peaking at masses smaller than 500 amu with a high
      mass tail extending up to about 3000 amu have been observed, yielding average
      weights around 900 amu. Such MWDs are in good agreement with previous mass
      spectrometric measurement, as well as with diffusion studies in solution. In
      addition, stable asphaltene aggregates have been detected giving rise to two
      broad bands in the mass spectrum corresponding to average molecular weights of
      2200-3100 amu and 15,000-19,000 amu, respectively. It is concluded that the
      strong aggregation propensity of asphaltenes is likely to be responsible for the
      apparent inconsistency between the MWD for these compounds determined by
      different groups in independent LDI-MS experiments. The reliability of different
      sample preparation procedures, including solvent-free methods, is discussed, and
      strategies are outlined that serve to apply the potentiality of LDI mass
      spectrometry to the characterization of covalent and non-covalent compounds in
      complex carbonaceous systems.

PMID- 17538978
TI  - Phase 2 randomized trial of primary endocrine therapy versus chemotherapy in
      postmenopausal patients with estrogen receptor-positive breast cancer.
AB  - BACKGROUND: Few studies have compared primary neoadjuvant endocrine therapy with
      neoadjuvant chemotherapy in breast cancer patients. The need for preoperative
      chemotherapy with doxorubicin or taxanes may be reduced in postmenopausal
      patients with estrogen receptor (ER)-positive and/or progesterone receptor (PgR)
      positive tumors. This randomized, controlled, phase 2 study evaluated the
      efficacy of neoadjuvant chemotherapy compared with endocrine treatment with
      aromatase inhibitors in postmenopausal women with ER-positive and/or PgR-positive
      breast cancer. METHODS: Eligible patients were randomly assigned to receive
      neoadjuvant anastrozole 1 mg/day (n = 61) or exemestane 25 mg/day (n = 60) for 3
      months or doxorubicin 60 mg/m(2) with paclitaxel 200 mg/m(2) (four 3-week
      cycles). Study end points included overall objective response determined by
      palpation, mammography, and ultrasound, and the number of patients who qualified
      for breast-conserving surgery and radiotherapy. RESULTS: Clinical objective
      response was 64% in the endocrine therapy and chemotherapy treatment groups.
      Median time to clinical response was 57 and 51 days with aromatase inhibitors and
      chemotherapy, respectively (P > .05). Rates of pathological complete response (3%
      vs 6%) and disease progression (9% vs 9%) did not differ significantly in the
      endocrine therapy or chemotherapy group, respectively (P > .05). Rates of breast
      conserving surgery were slightly higher in the endocrine group (33% vs 24%; P =
      .058). The most frequent toxicities from chemotherapy were alopecia (79%), grade
      3/4 neutropenia (33%), and grade 2 neuropathy (30%). Endocrine treatment was well
      tolerated. No deaths occurred during the preoperative treatment. CONCLUSIONS:
      Preoperative neoadjuvant endocrine therapy with aromatase inhibitors was well
      tolerated and resulted in rates similar to chemotherapy in overall objective
      response and breast-conserving surgery in postmenopausal women with ER-positive
      and/or PgR-positive tumors.

PMID- 17538979
TI  - Fiber introduction mass spectrometry: determination of pesticides in herbal
      infusions using a novel sol-gel PDMS/PVA fiber for solid-phase microextraction.
AB  - An application of the direct coupling of solid-phase microextraction (SPME) with
      mass spectrometry (MS), a technique known as fiber introduction mass spectrometry
      (FIMS), is described to determine organochlorine (OCP) and organophosphorus (OPP)
      pesticides in herbal infusions of Passiflora L. A new fiber coated with a
      composite of poly(dimethylsiloxane) and poly(vinyl alcohol) (PDMS/PVA) was used.
      Sensitive, selective, simple and simultaneous quantification of several OCP and
      OPP was achieved by monitoring diagnostic fragment ions of m/z 266
      (chlorothalonil), m/z 195 (alpha-endosulfan), m/z 278 (fenthion), m/z 263 (methyl
      parathion) and m/z 173 (malathion). Simple headspace SPME extraction (25 min) and
      fast FIMS detection (less than 40 s) of OCP and OPP from a highly complex herbal
      matrix provided good linearity with correlation coefficients of 0.991-0.999 for
      concentrations ranging from 10 to 140 ng ml(-1) of each compound. Good accuracy
      (80 to 110%), precision (0.6-14.9%) and low limits of detection (0.3-3.9 ng ml(
      1)) were also obtained. Even after 400 desorption cycles inside the ionization
      source of the mass spectrometer, no visible degradation of the novel PDMS/PVA
      fiber was detected, confirming its suitability for FIMS. Fast (ca 20 s) pesticide
      desorption occurs for the PDMS/PVA fiber owing to the small thickness of the film
      and its reduced water sorption.

PMID- 17538980
TI  - Birth weight and risk of cancer.
AB  - BACKGROUND: It is well established that prenatal biologic processes are important
      for the development of some childhood cancers, whereas less is known regarding
      their influence on adult cancer risk. High birth weight has been associated with
      risk of breast cancer, whereas studies of other specific cancers and all cancers
      together have been less conclusive. METHODS: The authors established a cohort of
      more than 200,000 men and women who were born between 1936 and 1975. Birth
      weights were obtained from school health records and information concerning
      cancer from the Danish Cancer Registry. Follow-up was performed between April 1,
      1968 and December 31, 2003. During 6,975,553 person-years of follow-up, a total
      of 12,540 primary invasive cancers were diagnosed. RESULTS: Analyses of site
      specific cancers revealed that the majority of cancers had a positive linear
      association with birth weight. Departures from a positive linear association were
      found to be statistically significant for cancers of the pancreas and bladder,
      which demonstrated a V-shaped association, and testicular cancer, which
      demonstrated an inverse association with birth weight. Excluding these 3
      exceptions, the trends for the individual cancer sites were not heterogeneous,
      and the overall trend was a relative risk of 1.07 (95% confidence interval, 1.03
      1.11) per 1000-g increase in birth weight. This trend was the same in men and
      women and in all age groups. CONCLUSIONS: A 7% increase in cancer risk was
      observed per 1000-g increase in birth weight. Few cancers demonstrated a
      nonlinear association with birth weight, and testicular cancer was found to be
      negatively associated with birth weight. The authors hypothesized that the
      biologic explanation behind the association between birth weight and cancer at
      different sites should be sought in a common pathway.

PMID- 17538981
TI  - Statistical shape analysis of differences in the shape of the corpus callosum
      between genders.
AB  - Sexual dimorphic characteristics, which play an important role in human evolution
      studies and biological research, can be studied morphologically and metrically.
      Geometric morphometrics allows a better assessment of morphological
      characteristics. Statistical shape analysis has a long history in neuroanatomical
      and other research. The aim of this study was to identify shape differences of
      the corpus callosum between genders. Landmark coordinate data were collected from
      two-dimensional magnetic resonance imaging scans of 93 homogeneously aged
      patients, 45 men and 48 women. These data were analyzed using Euclidean distance
      matrix analysis and thin plate spline analysis. The general shape variability of
      the corpus callosum of men was greater than that of women (men, 0.134; women,
      0.097). We found no significant difference between sexes in the general shape of
      the corpus callosum, but we did find significant differences in the distances
      between some landmarks. Deformation of the corpus callosum between men to women
      was mainly detected in the posterior of the corpus callosum. These results serve
      as a reference for future studies on shape alterations of the corpus callosum
      associated with certain conditions.

PMID- 17538982
TI  - The peritoneal mesothelium covering the genital tract and its ligaments in the
      female pig shows signs of active function.
AB  - The aim of this study was to describe the surface features of the peritoneal
      mesothelium covering the genital tract and adjacent ligaments of the sow to find
      signs of biosynthetic activation of cells. Surface features of the serosa
      covering the genital tract and adjacent ligaments from 14 cyclic sows, 7 in the
      follicular phase and 7 in the luteal phase of the estrous cycle, were examined by
      histology and scanning electron microscopy. Five additional sows, three in the
      follicular phase and two in the luteal phase of the estrous cycle, were examined
      by transmission electron microscopy (TEM). In this study, the presence of cells
      of the oviductal epithelium in the serosa of the infundibulum and the ampulla, as
      well as indications of a high functional activity of the mesothelial cells in the
      areas studied were two aspects that differed from the findings of previous works.
      Presence of endosalpingeal cells was observed in the serosal surface, showing
      cyclical variations with a predominance of either ciliated cells during the
      follicular phase or secretory cells during the luteal phase. Signs of high
      functional activity of the mesothelial cells included the predominance of
      cuboidal over flattened cells, a cytoplasm richly supplied with organelles, a
      dense microvillous coat, numerous primary cilia, and many secretory structures on
      the surface of cells. These results indicate that the serosa covering the genital
      area and the adjacent ligaments in the sow has an active epithelium whose
      coordinating role between reproductive tissues may be far more significant than
      previously thought.

PMID- 17538983
TI  - Nonadherence in inflammatory bowel disease: results of factor analysis.
AB  - BACKGROUND: The purpose of the study was to assess overall nonadherence to
      treatment among patients with Crohn's disease (CD) and ulcerative colitis (UC) in
      a single tertiary center. METHODS: A total of 177 patients were enrolled in this
      study (84 males, 93 females; 117 CD, 60 UC). Patients were interviewed about
      their nonadherent behavior and their answers were analyzed using factor analysis.
      Urine samples were collected from a subcohort of 47 patients treated by
      mesalamine to verify the presence of 5-ASA or its metabolites. RESULTS: Overall
      intentional nonadherence was reported by 38.9% of patients; 18.6% of the patients
      discontinued the treatment at least once. Intentional dose reduction was reported
      by 18% of patients; 14.7% of patients occasionally did not refill their
      medications on time. There were no differences in adherence between males and
      females, disease type, previous bowel surgery, or marital, smoking, and
      nonsmoking status. More than 38% of patients reported unintentional nonadherence.
      Factor analysis proved that nonadherence increased with a higher education level
      of the patients and decreased with older age. Adverse drug effects strongly
      contributed to nonadherence. Nonadherent patients were more likely to be
      chronically active or in relapse (tau = 0.212; P = 0.002). In the group of 47
      patients whose urine was analyzed, 6 cases (12.7%) were negative for mesalamine
      or its metabolite. CONCLUSIONS: The overall intentional nonadherence with medical
      therapy is relatively high among IBD patients and should be taken into account
      when a patient's response to treatment is unsatisfactory. Therefore, problems of
      nonadherence should be discussed with all IBD patients.

PMID- 17538984
TI  - Effect of inflammatory bowel disease classification changes on NOD2 genotype
      phenotype associations in a population-based cohort.
AB  - BACKGROUND: NOD2 mutations are associated with Crohn's disease (CD) in Caucasian
      clinic-based cohorts. Data from population-based cohorts are limited. Clinic
      based studies may overestimate this association. Genotype-phenotype relationships
      are yet to be assessed using the Montreal classification. We hypothesized that
      the NOD2-CD association would be weaker in a population-based cohort, and that
      the Montreal classification would strengthen genotype-phenotype associations.
      METHODS: A population-based case-control study was performed including 91% of all
      people in Canterbury, New Zealand, with inflammatory bowel disease (IBD); NOD2
      genotyping was performed and patients were phenotyped according to the Vienna and
      Montreal classification systems. RESULTS: The NOD2 genotype was available on 684
      CD, 643 ulcerative colitis (UC), 36 indeterminate colitis/IBDU (IBD unclassified)
      patients, and 201 controls. Control frequencies for the 702W, 908R, and 1007fs
      alleles were 0.030, 0.012, and 0.010, respectively, compared with 0.074, 0.027,
      and 0.040 for CD. The 702W (P = 0.001) and 1007fs (P = 0.002) alleles were
      significantly associated with CD. Younger age of diagnosis (<17 years) was
      associated with 1 (odds ratio (OR) 1.9 [95% confidence intervals 0.98-3.6]) or 2
      (OR 6.5 [2.3-18.6]) NOD2 mutations compared with diagnosis >40 years. Ileal
      disease was most strongly associated with NOD2 mutations (1 mutation OR 3.9 [2.4
      6.3], 2 mutations OR 6.7 [2.4-18.5]). Penetrating disease was associated with
      NOD2 mutations using the Montreal but not the Vienna classification. CONCLUSIONS:
      The association between NOD2 mutations and CD was found to be weaker in our
      population-based cohort than in previous studies that used referral-based
      cohorts. Application of the Montreal classification led to a strengthening of the
      NOD2 genotype-phenotype association.

PMID- 17538985
TI  - Carcinoid tumors are 15 times more common in patients with Crohn's disease.
AB  - BACKGROUND: The coexistence of intestinal neoplasms with Crohn's disease (CD) has
      been reported, but the evidence of an increased risk of carcinoid tumor with
      Crohn's disease has been mixed. We present 4 patients with CD with associated
      carcinoid tumor. METHODS: The charts of 111 patients with CD who had undergone
      resection between June 2001 and March 2005 were reviewed. The number of
      incidental carcinoid tumors in patients who underwent an appendectomy was used as
      a control. RESULTS: Four cases of carcinoid tumor discovered in patients at
      resection for CD were identified. None had metastatic disease or carcinoid
      syndrome. These included 1 cecal (1 mm), 2 appendiceal (3 and 7 mm), and 1
      transverse colon (7 mm) carcinoid tumors. None of the carcinoid tumors were
      identified in regions of active Crohn's disease. The incidence of carcinoid tumor
      in patients with Crohn's disease was 4 of 111 (3.6%). In comparison, 3 of 1199
      patients (0.25%) who had appendectomies were identified as having appendiceal
      carcinoid tumor. Crohn's disease was associated with an increased incidence of
      carcinoid tumor; OR 14.9 (95% CI 2.5-102.5), P<0.0001. CONCLUSIONS: There was a
      significantly increased incidence of carcinoid tumor in our Crohn's patients
      compared to the control patients. None of the carcinoid tumors developed in areas
      of Crohn's disease. This suggests that the development of carcinoid tumors may be
      secondary to distant proinflammatory mediators, rather than a local inflammatory
      effect from adjacent Crohn's disease. Patients with CD may be at increased risk
      of developing a carcinoid tumor.

PMID- 17538986
TI  - New drugs: kids come first; con: first adults, then children.

PMID- 17538987
TI  - Initial clinical results of orthotopic liver transplantation for hepatic alveolar
      echinococcosis.
AB  - We analyzed the features of 7 patients who underwent orthotopic liver
      transplantation (OLT) from April 2001 to April 2006 for incurable hepatic
      alveolar echinococcosis (AE) in view of the technical features of the OLT,
      incidence, and type of complications, as well as patient survival. All 7 patients
      had biliary diseases that resulted from parasitic involvement of the hilum or a
      large parasitic lesion that invaded the lobes of the liver due to parasitic
      involvement of the hepatic veins, which are all typical syndromes of hepatic AE.
      Five patients had previously undergone surgery for hepatic AE and were at the end
      stage of liver functional disorder. Four patients' operations were performed
      under venovenous bypass. The mean duration of surgery was 9.1 hours. After
      transplantation, one patient experienced biliary leakage but was successfully
      treated with reoperation. One patient died 21 days later of septicemia caused by
      pneumonia and multiple organ failure, and another patient died 3 months after OLT
      from heart failure. The other 5 patients are alive and in good condition after
      transplantation. Although the transplantation procedure was more difficult than
      usual in these patients, most achieved prolonged survival and a good quality of
      life. This study suggests that OLT is feasible for incurable AE of the liver and
      that this procedure ensures a good clinical outcome.

PMID- 17538988
TI  - Thrombolysis for early hepatic artery thrombosis: definitive therapy or
      diagnostic aid?

PMID- 17538989
TI  - Transient portacaval shunt for a small-for-size graft in living donor liver
      transplantation.

PMID- 17538990
TI  - Towards a better liver transplant allocation system.

PMID- 17538992
TI  - Computation of nitroxide-nitroxide distances in spin-labeled DNA duplexes.
AB  - Nanometer distances in nucleic acids can be measured by EPR using two 1-oxyl
      2,2,5,5-tetramethylpyrroline radicals, with each label attached via a methylene
      group to a phosphorothioate-substituted backbone position as one of two
      phosphorothioate diastereomers (R(P) and S(P)). Correlating the internitroxide
      distance to the geometry of the parent molecule requires computational analysis
      of the label conformers. Here, we report sixteen 4-ns MD simulations on a DNA
      duplex d(CTACTGCTTTAG) .d(CTAAAGCAGTAG) with label pairs at C7/C19, T5/A17, and
      T2/T14, respectively. For each labeled duplex, four simulations were performed
      with S(P)/S(P), R(P)/R(P), S(P)/R(P), and R(P)/S(P) labels, with initial all
      trans label conformations. Another set of four simulations was performed for the
      7/19-labeled duplex using a different label starting conformation. The average
      internitroxide distance r(MD) was within 0.2 A for the two sets of simulations
      for the 7/19-labeled duplex, indicating sufficient sampling of conformational
      space. For all three labeled duplexes studied, r(MD) agreed with experimental
      values, as well as with average distances obtained from an efficient conformer
      search algorithm (NASNOX). The simulations also showed that the labels have
      conformational preferences determined by the linker chemistry and label-DNA
      interactions. These results establish computational algorithms that allow use of
      the 1-oxyl-2,2,5,5-tetramethylpyrroline label for mapping global structures of
      nucleic acids.

PMID- 17538993
TI  - Impact of human leukocyte antigen mismatching on outcomes of living donor liver
      transplantation for primary biliary cirrhosis.

PMID- 17538994
TI  - Living donor liver transplantation of the right lobe for hepatocellular carcinoma
      in cirrhosis in a European center.
AB  - Living donor liver transplantation of the right lobe might offer the possibility
      to extend the eligibility criteria of patients with hepatocellular carcinoma
      (HCC) in cirrhosis without penalizing patients who are waiting for a graft from a
      deceased donor. From 1988 to 2005, surgical treatment of HCC was performed in 580
      patients (187 transplantation, 393 resection) in a European center. In the
      transplantation group, 21 patients with HCC in cirrhosis underwent LDLT (11% of
      all transplantations for HCC; 22% of 96 LDLT). Solitary HCC were accepted
      irrespective of their diameter unless vascular invasion was detectable. Multiple
      HCC nodes were considered acceptable up to a diameter of the largest node of 6 cm
      and a total tumor diameter of 15 cm. The median follow-up period was 26 months
      (range, 1-65 months). Vascular invasion had occurred in 12 patients (57%). One
      patient (4.8%) died within 60 days after transplantation from sepsis. Rates of 3
      year survival and 3-year recurrence-free survival were 68% and 64%, respectively.
      Overall 3-year survival rates in patients with HCC in cirrhosis not meeting the
      Milan criteria (n = 13) or the San Francisco criteria (n = 8) were 62% and 53%,
      respectively. LDLT is a safe procedure. However, small sample sizes do not yet
      permit a definitive comparison to be made between the former results obtained
      after cadaveric donation. So far, the outcome of the patients is in favor of a
      careful extension of the selection criteria for HCC in cirrhosis.

PMID- 17538995
TI  - Systematic grading of surgical complications in live liver donors.

PMID- 17538996
TI  - Liver transplantation for hepatocellular carcinoma: the hepatitis C quandary.

PMID- 17538997
TI  - Prognostication in acute liver failure: a tool or an anchor?

PMID- 17538998
TI  - De novo nonalcoholic fatty liver disease after liver transplantation.

PMID- 17538999
TI  - Pharmacokinetics of mycophenolic acid in liver transplant patients after
      intravenous and oral administration of mycophenolate mofetil.
AB  - The bioavailability of mycophenolic acid (MPA) after oral administration of
      mycophenolate mofetil (MMF) has been reported to be more than 90% in healthy
      volunteers, and in kidney and thoracic organ transplant patients. Such
      information is limited in liver transplant (LTx) patients. The present study
      compares the pharmacokinetics of MPA after intravenous (IV) and oral
      administrations of MMF in LTx recipients. Pharmacokinetic parameters were
      calculated using WinNonlin software. A total of 12 deceased donor LTx patients
      initially received IV MMF and were switched to oral MMF after 2-7 days (mean, 3.3
      +/- 1.7) when oral feeds were started. Multiple blood samples were drawn
      immediately prior to and after IV or oral MMF and the plasma concentration of MPA
      was measured. The mean peak plasma concentrations and the area under the plasma
      concentration vs. time curve (AUC) were significantly higher after IV MMF
      compared to oral MMF (peak plasma concentrations of 10.7 +/- 2.1 microg/mL for IV
      vs. 4.5 +/- 2.8 microg/mL for oral; P = 0.0001; and AUC of 28.9 +/- 7.1 microg .
      hr/mL for IV vs. 12.8 +/- 4.2 microg . hr/mL for oral; P = 0.0001). The oral
      bioavailability of MPA was 48.5 +/- 18.7%. The systemic clearance, half-life, and
      steady state volume of distribution of MPA were 26.9 +/- 6 L/hour, 5.5 hours, and
      85 liters, respectively. The terminal disposition half-life was not significantly
      different between the 2 routes of administration. In conclusion, during the early
      postoperative period, LTx recipients have MPA exposure with oral MMF of less than
      half that of IV MMF. Use of IV MMF immediately post-LTx may provide an
      immunological advantage.

PMID- 17539000
TI  - Three-quarters of right liver donors experienced postoperative complications.
AB  - A donor right hepatectomy (RH) is associated with a higher rate of morbidity than
      a left hepatectomy. Therefore, the precise morbidity should be known to improve
      the success of donor RH implementation. However, the rate of complication varies
      according to the individual definition of morbidity. This study prospectively
      analyzed the outcomes of 83 consecutive living donor RHs between January 2002 and
      July 2004 using a standardized classification of the severity of complications.
      The morbidity was classified using the modified Clavien system: grade I for minor
      complications; grade II for potentially life-threatening complications requiring
      pharmacological treatment; grade III for complications requiring invasive
      intervention; grade IV for complications causing organ dysfunction requiring
      intensive care unit management; and grade V complications resulting in the death
      of the patient. The donors were followed-up regularly for at least 12 months. No
      donor death or relaparotomy was noted. Overall, 65 out of 83 donors (78.3%)
      experienced postoperative complications: grades I, II, III, IV, and V
      complications in 64 (77.1%), 11 (13.3%), 1 (1.2%), 0, and 0 patients,
      respectively. The most common grade I complications were hyperbilirubinemia (n =
      31) and pleural effusion (n = 31), and bile leakage in grade II (n = 7). The
      bilirubin and alanine aminotransferase levels were normal in 92.7% of donors at
      the 1-year follow-up. In conclusion, although most of these adverse events were
      minor and self-limited, 78% of right liver donors still experienced morbidity.
      Therefore, continuous standardized reporting of the donor morbidity as well as
      meticulous surgery and intensive care are essential for the success of donor RH
      implementation.

PMID- 17539001
TI  - Survival outcomes in liver transplantation for hepatocellular carcinoma,
      comparing impact of hepatitis C versus other etiology of cirrhosis.
AB  - The incidence of hepatocellular carcinoma (HCC) is on the rise worldwide as the
      most common primary hepatic malignancy. In the US approximately one half of all
      HCC is related to Hepatitis C virus (HCV) infection. The relationship between the
      primary disease and HCC recurrence after liver transplantation is unknown. We
      hypothesized that the primary hepatic disease underlying the development of
      cirrhosis and HCC would be associated with the risk of recurrent HCC after
      transplantation. A retrospective review was conducted of all primary liver
      transplants performed at the University of Rochester Medical Center from May 1995
      through June 2004. The pathology reports from the native livers of 727 recipients
      were examined for the presence of HCC. There were 71 liver transplant recipients
      with histopathological evidence of HCC. These patients were divided in two groups
      on the basis of HCV status. Group 1 consisted of 37 patients that were both HCV
      and HCC positive, and Group 2 consisted of 34 patients that were HCC positive but
      HCV negative. Patient characteristics were analyzed, as well as number of tumors,
      tumor size, presence of vascular invasion, lobe involvement, recipient
      demographics, donor factors, pretransplantation HCC therapy, rejection episodes,
      and documented HCC recurrence and treatment. There were no statistically
      significant differences between the 2 groups, with the exception of recipient age
      and the presence of hepatitis B coinfection. The tumor characteristics of both
      groups were similar in numbers of tumors, Milan criteria status, vascular
      invasion, incidental HCC differentiation, and largest tumor size. The HCV
      positive population had a far lower patient survival rate with patient survival
      in Group 1 at 1, 3, and 5 years being 81.1%, 57.4%, and 49.3% respectively,
      compared with 94.1%, 82.8%, and 76.4% in Group 2 (p = 0.049). Tumor-free survival
      in Group 1 at 1, 3, and 5 years was 70.3%, 43%, and 36.8% respectively, vs.
      88.1%, 73%, and 60.8% in Group 2. In a subgroup analysis, tumor-free survival was
      further examined by stratifying the patients on the basis of Milan criteria.
      Group 1 patients outside of Milan criteria had a statistically lower tumor-free
      survival. By contrast, there was no statistical difference in tumor-free survival
      in Group 2 patients stratified according to Milan criteria. Cox regression
      analysis identified HCV and vascular invasion as significant independent
      predictors of tumor-free survival. Our results suggest that Milan selection
      criteria may be too limiting and lose their predictive power when applied to
      patients without HCV infection.

PMID- 17539002
TI  - MELD is superior to King's college and Clichy's criteria to assess prognosis in
      fulminant hepatic failure.
AB  - Assessment of prognosis in fulminant hepatic failure (FHF) is essential for the
      need and appropriate timing of orthotopic liver transplantation (OLT). In this
      study we investigated the prognostic efficacy of King's College criteria,
      Clichy's criteria, Model for End-Stage Liver Disease (MELD), and Pediatric End
      Stage Liver Disease (PELD) in 120 consecutive patients with FHF. Survival with
      medical therapy (18%), death without OLT (15%), and receipt of a liver transplant
      were similar in adults (n = 64) and children (n = 56). MELD scores were
      significantly higher in patients who died compared to those who survived without
      OLT, both in adults (38 +/- 7 vs. 26 +/- 7, P = 0.0003) and children (39 +/- 7
      vs. 23 +/- 6, P = 0.0004). Using logistic regression analysis in this cohort of
      patients, concordance statistics were significantly higher for MELD (0.95) and
      PELD (0.99) when compared to King's College (0.74) and Clichy's criteria (0.68).
      When data was analyzed in a Cox model including patients receiving transplants
      and censoring the time from admission, the concordance statistic for MELD (0.77)
      and PELD (0.79) remained significantly higher than that of King's College
      criteria but not higher than that of Clichy's criteria. In conclusion, this study
      is the first to show that MELD and PELD are superior to King's College and
      Clichy's criteria to assess prognosis in FHF. However, because data was generated
      from a single center and included a rather low number of patients who survived or
      died without OLT, further confirmation of our findings is required.

PMID- 17539003
TI  - Hepatorenal syndrome: a proposal for kidney after liver transplantation (KALT).
AB  - Hepatorenal syndrome (HRS) is a well-recognized complication of end-stage liver
      disease. Once thought to be a reversible condition with liver transplantation
      (LT) alone, HRS may directly contribute to the requirement for long-term dialysis
      posttransplant. As a result, discussion has now focused on whether or when a
      kidney allograft should be considered for these patients. Using the International
      Ascites Club guidelines with a pretransplant serum creatinine (SCr) >2.0 mg/dL to
      define HRS, 130 patients undergoing LT over a 10-yr period were identified, for
      an overall incidence of 9%. Patient survival rates at 1, 3, and 5 yr were 74%,
      and 68%, and 62%, respectively. Survival was significantly worse when compared to
      non-HRS patients undergoing LT over the same study period (P = 0.0001). For
      patients presenting with type 2 HRS, 7 patients (6%) developed irreversible
      kidney failure posttransplant compared to 0.34% in the non-HRS population (P <
      0.0001). Five of these patients died within 1 yr with a median survival time of
      139 days. Combined liver and kidney transplantation (CLKT) for patients with HRS
      is not recommended. However, an improvement in outcome can be accomplished by
      addressing those patients who require dialysis greater than 60 days
      posttransplant. We propose a role for kidney after liver transplantation (KALT)
      in select HRS patients.

PMID- 17539004
TI  - Long-term results of living donor liver transplantation for glycogen storage
      disorders in children.
AB  - Liver transplantation (LT) may be indicated in glycogen storage disorders (GSD)
      when medical treatment fails to control the metabolic problems or when hepatic
      adenomas develop. We present our institutional experience with living donor LT
      (LDLT) for children with GSD. A total of 244 patients underwent primary LDLT at
      our institution from June 1994 to December 2005. A total of 12 (5%) children (8
      female and 4 male) were afflicted with GSD and were not responsive to medical
      treatment. Nine patients had GSD type I and 3 had GSD type III. The median age at
      the time of transplantation was 7.27 yr (range, 2.4-15.7). All patients presented
      with metabolic abnormalities, including hypoglycemia, and lactic acidosis. In
      addition, 4 patients presented with growth retardation. A total of 11 patients
      received left lobe grafts and 1 received a right lobe graft. The mean graft-to
      recipient weight ratio was 1.25 (range, 0.89-1.61). Two patients had hepatic vein
      stenoses that were treated by balloon dilatation; 1 patient had bile leak, which
      settled spontaneously. The overall surgical morbidity rate was 25%. Three
      patients had hepatic adenomas in the explanted liver. There was a single
      mortality at 2 months posttransplantation due to acute pancreatitis and sepsis.
      The mean follow up was 47.45 months. The metabolic abnormalities were corrected
      and renal function remained normal. In patients with growth retardation, catch-up
      growth was achieved posttransplantation. In conclusion, LDLT is a viable option
      to restore normal metabolic balance in patients with GSD when medical treatment
      fails. Long-term follow-up after LT for GSD shows excellent graft and patient
      survival.

PMID- 17539005
TI  - Sirolimus-induced pneumonitis following liver transplantation.
AB  - Sirolimus-induced pneumonitis has emerged as a potentially serious complication
      in renal transplantation but only single case reports of this condition have been
      described after liver transplantation (LT), where experience with sirolimus is
      relatively limited. We report our experience, the largest to date, of sirolimus
      induced pneumonitis following LT. Between 1999 and 2006, 186 liver transplant
      patients received sirolimus-based immunosuppression, after initial therapy with
      calcineurin inhibitors (CNIs). All cases of sirolimus-induced pneumonitis were
      recorded and a retrospective review of the case notes of such patients was
      undertaken for the purpose of this analysis. Of 186 liver transplant patients
      receiving sirolimus, 4 (2.2%) developed pneumonitis that was attributed to the
      drug; the time from starting sirolimus to presentation was varied (1.5-30
      months). The most common presenting symptoms were dyspnea, cough and fatigue. The
      median sirolimus level at the time of diagnosis was 9.7 ng/mL (range, 7-19.5
      ng/mL). All patients in the series underwent thoracic computed tomography, which
      showed similar changes in all patients, and lung biopsy, which revealed features
      consistent with a drug-induced pneumonitis. In all 4 patients, sirolimus-induced
      pneumonitis resolved following cessation of therapy but took weeks to months for
      complete recovery. In conclusion, sirolimus-induced pneumonitis occurred in at
      least 2% of liver transplant recipients and should be suspected in patients who
      develop respiratory symptoms while on sirolimus. Although it may be life
      threatening, early recognition and cessation of sirolimus can lead to complete
      resolution of pneumonitis.

PMID- 17539006
TI  - A new priority policy for patients with hepatocellular carcinoma awaiting liver
      transplantation within the model for end-stage liver disease system.
AB  - The best prioritization of patients with hepatocellular carcinoma (HCC) waiting
      for liver transplantation under the model for end-stage liver disease (MELD)
      allocation system is still being debated. We analyzed the impact of a MELD
      adjustment for HCC, which consisted of the addition of an extra score (based on
      the HCC stage and waiting time) to the native MELD score. The outcome was
      analyzed for 301 patients with chronic liver disease listed for liver
      transplantation between March 1, 2001 and February 28, 2003 [United Network for
      Organ Sharing (UNOS)-Child-Turcotte-Pugh (CTP) era, 163 patients, 28.8% with HCC]
      and between March 1, 2003 and February 28, 2004 (HCC-MELD era, 138 patients,
      29.7% with HCC). In the HCC-MELD era, the cumulative dropout risk at 6 months was
      17.6% for patients with HCC versus 22.3% for those patients without HCC (P = NS),
      similar to that in the UNOS-CTP era. The cumulative probability of
      transplantation at 6 months was 70.3% versus 39.0% (P = 0.005), being higher than
      that in the UNOS-CTP era for patients with HCC (P = 0.02). At the end of the HCC
      MELD era, 12 patients with HCC (29.3%) versus 57 without HCC (58.8%) were still
      on the list (P = 0.001). Both native and adjusted MELD scores were higher (P <
      0.05) and progressed more in patients with HCC who dropped out than in those who
      underwent transplantation or remained on the list (the initial-final native MELD
      scores were 17.3-23.1, 15.5-15.6, and 12.8-14.1, respectively). The patients
      without HCC remaining on the list showed stable MELD scores (initial-final: 15.1
      15.4). In conclusion, the present data support the strategy of including the
      native MELD scores in the allocation system for HCC. This model allows the timely
      transplantation of patients with HCC without severely affecting the outcome of
      patients without HCC.

PMID- 17539007
TI  - Can the model for end-stage liver disease be used to predict the prognosis in
      patients with Budd-Chiari syndrome?
AB  - The model for end-stage liver disease (MELD) is a widely accepted and objective
      scoring system for end-stage liver disease (ESLD) but has never been evaluated
      for Budd-Chiari syndrome (BCS). We investigated whether MELD can be used to
      predict survival in patients with BCS. Patients with BCS (n = 237) were obtained
      from a large international study. Patients with ESLD (n = 281) were used to
      compare the discriminative ability of MELD in BCS versus other chronic liver
      diseases. MELD and the Rotterdam BCS index, a recently developed prognostic index
      for BCS, were calculated with standard equations. Receiver operating
      characteristic curves and concordance statistics (c-statistics) were used to
      assess the models' ability to predict 1-year survival. The median MELD score was
      12.5 (range = -7.4 to 43.4) for BCS and 11.3 (-3.0 to 49.5) for ESLD (P = 0.12).
      The c-statistic of MELD in BCS was 0.695 [95% confidence interval (CI) = 0.59
      0.80], in contrast to 0.848 (95% CI = 0.80-0.90) in ESLD. Survival was
      significantly poorer in ESLD than in BCS (P < 0.001). The c-statistic of the
      Rotterdam BCS index was 0.760 (95% CI = 0.67-0.85). The correlation between MELD
      and the Rotterdam BCS index was 0.61, and most of the discrepancy existed in BCS
      patients with a high prevalence of ascites and encephalopathy and preserved liver
      function. The addition of ascites and encephalopathy to MELD improved the c
      statistic to 0.751 (95% CI = 0.65-0.85). In conclusion, MELD showed a suboptimal
      discriminative ability to predict survival in BCS. This was explained by the
      highly variable degree of liver dysfunction and hence clinical outcome in BCS in
      contrast to ESLD.

PMID- 17539008
TI  - Long-term follow-up of portopulmonary hypertension: effect of treatment with
      epoprostenol.
AB  - Moderate to severe portopulmonary hypertension (PPHTN) increases the risks of
      orthotopic liver transplantation (OLT). Epoprostenol is an effective treatment of
      PPHTN, but long-term effects on pulmonary hemodynamics or liver function in PPHTN
      are poorly defined. We sought to describe the long-term effects of treatment with
      or without epoprostenol on pulmonary hemodynamics, liver biochemistries, and
      survival in patients with moderate to severe PPHTN at a single center. A large
      retrospective cohort was identified with moderate to severe PPHTN diagnosed
      before OLT. Baseline and follow-up pulmonary hemodynamics and liver
      biochemistries were compared and outcomes assessed. Nineteen patients were
      treated with epoprostenol and 17 were not treated with epoprostenol. There were
      significant improvements in mean pulmonary artery pressure (MPAP, 48.4-36.1 mm
      Hg; P < 0.0001), pulmonary vascular resistance (PVR, 632-282 dynes . s . cm(-5);
      P < 0.0001), and cardiac output (5.7 to 7.7 L/min; P = 0.0009) with epoprostenol
      after a median of 15.4 months. Liver biochemistries did not change significantly,
      and survival did not seem to differ between the 2 groups (hazard ratio, 0.85; P =
      0.77). In the epoprostenol group, patients who survived had greater absolute
      changes in MPAP, transpulmonary gradient, and PVR than those who died. Two
      patients in the epoprostenol group successfully underwent OLT. Long-term
      epoprostenol therapy greatly improves pulmonary hemodynamics in patients with
      PPHTN. Liver biochemistries are not greatly changed. Survival seemed not to
      differ between treatment groups. A minority of patients treated with epoprostenol
      will improve sufficiently to undergo OLT.

PMID- 17539009
TI  - Psychological strain in urgent indications for living donor liver
      transplantation.
AB  - The ethical soundness of living donor liver transplantation (LDLT) in urgent
      indications is still under discussion. The aim of the survey was to investigate
      the psychological distress of donors in cases of hepatocellular carcinoma (HCC)
      or acute liver failure (ALF). In a prospective multicenter study (n = 123),
      health-related quality of life (QOL), anxiety, and depression were measured. The
      psychological distress of donors was correlated to the degree of urgency of the
      recipients' indication, which was classified as nonurgent, HCC, or ALF. During
      the donor evaluation prior to LDLT, the donors with recipients for HCC and ALF
      demonstrated significantly reduced mental QOL in comparison to donors for a
      nonurgent indication and to the German normative sample. Compared to healthy
      controls, anxiety and depression were significantly increased in donors for ALF.
      Three months after the transplantation, scores for mental QOL as well as for
      anxiety and depression improved and were within the normal range for the whole
      group as well as for the ALF donors. In conclusion, the psychological burden was
      temporary in nature. Our findings can be considered as arguments for the current
      practice to address family members as donors in cases of HCC and ALF.

PMID- 17539010
TI  - Posttransplantation lymphoproliferative disorder--the great mimic in liver
      transplantation: appraisal of the clinicopathologic spectrum and the role of
      Epstein-Barr virus.
AB  - Case series describing posttransplantation lymphoproliferative disorder (PTLD)
      after liver transplantation (LTx) have been limited in number because of the
      rarity of the disorder. The prevalence of Epstein-Barr virus (EBV) infection and
      its detection, the clinical and histological diversity of disease, and survival
      have varied. The aim of this study is to define the clinical and pathological
      spectrum of PTLD after LTx, and evaluate EBV prevalence, impact of infection, and
      patient survival. A retrospective analysis of all LTx recipients at our
      institution diagnosed with PTLD from January 1990 until May 2005, recording
      clinical presentations, times of presentation after transplantation, histological
      findings, results of EBV assessment, and survival, as well as the
      interrelationship of these variables. Among 621 LTx recipients were 22 cases of
      PTLD in 21 patients, of whom 5 were children and 16 were adults. Extranodal
      disease was present in 17 of 22 cases (77%) involving a wide variety of organ
      systems, while 5/22 (23%) had lymphadenopathy. The spectrum of PTLD
      histopathology was equally varied. In situ hybridization for EBV showed
      negativity in 8 of 13 (62%) and positivity in 5 of 13 (38%) cases tested. Neither
      time interval from transplantation to presentation (median 33 months) nor
      mortality (average 32%) was influenced by EBV status. In conclusion, PTLD in LTx
      recipients is predominantly extranodal and can involve a wide variety of organ
      systems, which may confound initial diagnosis. The lymphoproliferative
      histological spectrum is also diverse. Nowadays, PTLD is frequently EBV-negative,
      and EBV status does not appear to influence clinical or pathological
      presentation, or survival.

PMID- 17539011
TI  - Human stem cells, chromatin, and tissue engineering: boosting relevancy in
      developmental toxicity testing.
AB  - Risk assessment derives its confidence from toxicology research that is based on
      relevancy to human health. This article focuses on two highly topical areas of
      current scientific research, stem cells and chromatin biology, which present new
      avenues for preclinical and clinical applications, and the frontier role of
      tissue engineering and regeneration. Appreciating the utility and necessity of
      chromatin and human somatic stem cells as research tools and looking toward
      tissue engineering may close the uncertainty gaps between animal and human cross
      species toxicology evaluations. The focus will be on developmental toxicology
      applications, but appropriate extrapolation to any other areas of toxicology can
      be made. We further provide background on basic biology of these three areas and
      examples of how early life exposure to known and potential environmental
      toxicants induce malformations, childhood and adult-onset diseases, through
      aberrant chromatin modification of critical gene expressions (acute lymphocyte
      leukemia, heavy-metal nickel and cadmium-associated defects, and reproductive
      tract malformations and carcinomas induced by the synthetic estrogen,
      diethylstilbestrol).

PMID- 17539012
TI  - Environmental agents affect skeletal growth and development.
AB  - In this treatise we will examine complexities in the development and function of
      cells of the musculoskeletal system. Specifically, the role of chondrocytes and
      their ontogeny and osteoblasts and their ontogeny will be discussed as they
      regulate cartilage and bone formation. This background information will provide
      the foundation for evaluating the effects of environmental toxicants on skeletal
      development. A number of agents such as heavy metals (i.e. lead) and polycyclic
      aromatic hydrocarbons (i.e. pesticides and cigarette smoke) interact with cells
      of the skeletal system and adversely affect development. These agents have not
      been of major research interest, nevertheless, given changes in the environmental
      profile of the United States and other developed countries, it is important that
      we understand their effects in bone and cartilage. Research in this area will
      identify strategies that may be used to help prevent musculoskeletal diseases due
      to toxicant exposure.

PMID- 17539013
TI  - Does middle hepatic vein omission in a right split graft affect the outcome of
      liver transplantation? A comparative study of right split livers with and without
      the middle hepatic vein.
AB  - Preservation of the middle hepatic vein (MHV) for a right split liver
      transplantation (SLT) in an adult recipient is still controversial. The aim of
      this study was to evaluate the graft and patient outcomes after liver
      transplantation (LT) using a right split graft, according to the type of venous
      drainage. From February 2000 to May 2006, 33 patients received 34 cadaveric right
      split liver grafts. According to the type of recipient pairs (adult/adult or
      adult/child), the right liver graft was deprived of the MHV or not. The first
      group (GI, n = 15) included grafts with only the right hepatic vein (RHV)
      outflow, the second (GII, n = 18) included grafts with both right and MHV
      outflows. The 2 groups were similar for patient demographics, initial liver
      disease, and donor characteristics. In GI and GII, graft-to-recipient-weight
      ratio (GRWR) was 1.2 +/- 0% and 1.6 +/- 0.3% (P < 0.05), and cold ischemia time
      was 10 hours 55 minutes +/- 2 hours 49 minutes and 10 hours 47 minutes +/- 3
      hours 32 minutes, respectively (P = not significant). Postoperative death
      occurred in 1 patient in each group. Vascular complications included anastomotic
      strictures: 2 portal vein (PV), 1 hepatic artery (HA), and 1 RHV anastomotic
      strictures; all in GI. Biliary complications occurred in 20% and 22% of the
      patients, in GI and GII, respectively (P = not significant). There were no
      differences between both groups regarding postoperative outcome and blood tests
      at day 1-15 except for a significantly higher cholestasis in GI. At 1 and 3 yr,
      patient survival was 94% for both groups and graft survival was 93% for GI and
      90% for GII (P = not significant). In conclusion, our results suggest that adult
      right SLT without the MHV is safe and associated with similar long-term results
      as compared with those of the right graft including the MHV, despite that early
      liver function recovered more slowly. Technical refinements in outflow drainage
      should be evaluated in selected cases.

PMID- 17539014
TI  - Protein electron transfer (mechanism and reproductive toxicity): iminium,
      hydrogen bonding, homoconjugation, amino acid side chains (redox and charged),
      and cell signaling.
AB  - This contribution presents novel biochemical perspectives of protein electron
      transfer (ET) with focus on the iminium nature of the peptide link, along with
      relationships to reproductive toxicity. The favorable influence of hydrogen
      bonding on protein ET has been widely documented. Hydrogen bonding of the
      zwitterionic peptide enhances iminium character. A wide array of such bonding
      agents is available in vivo, with many reports on the peptide link itself. ET
      proceeds along the backbone, due in part, to homoconjugation. Redox amino acids
      (AAs), mainly tyrosine (Tyr), tryptophan (Typ), histidine (His), cysteine (Cys),
      disulfide, and methionine (Met), are involved in the competing processes for
      radical formation: direct hydrogen atom abstraction versus electron and proton
      loss. It appears that the radical or radical cation generated during the redox
      process is capable of interacting with n-electrons of the backbone. Beneficial
      effects of cationic AAs impact the conduction process. A relationship apparently
      exists involving cell signaling, protein conduction, and radicals or electrons.
      In addition, the link between protein ET and reproductive toxicity is examined. A
      key element is the role of reactive oxygen species (ROS) generated by protein ET.
      There is extensive evidence for involvement of ROS in generation of birth
      defects. The radical species arise in protein mainly by ET transformations by
      enzymes, as illustrated in the case of alcoholism.

PMID- 17539015
TI  - Rapidly progressive recurrent hepatitis C virus infection starting 9 days after
      liver transplantation.
AB  - Early histological recurrence of hepatitis C after liver transplantation (LT) has
      a negative impact on patient and graft survival. We report a case of histological
      recurrence of HCV occurring in the second week after LT. A 75-year-old woman with
      chronic HCV and hepatocellular carcinoma underwent LT with an organ from a 75
      year-old HCV-negative deceased donor. After an uneventful early postoperative
      period, an increase in the transaminases was observed, and on postoperative day 9
      day, the alanine aminotransferase (ALT) was 673 IU/mL and aspartate
      aminotransferase (AST) 300 IU/mL, with normal alkaline phosphatase and bilirubin.
      Analysis of liver biopsy samples showed diffuse necroinflammatory changes with
      acidophilic bodies and concomitant mild acute cellular rejection. Subsequently
      there was a further increase in the transaminases, and on postoperative day 13,
      the AST rose to 445 IU/mL and ALT to 992 IU/mL. Repeat biopsy was performed, and
      analysis of the samples revealed lymphocytic portal inflammation with lymphoid
      aggregates and mild interface hepatitis, parenchymal necrosis, activation of
      sinusoidal lining cells, and mild steatosis. The biopsy sample was characteristic
      for HCV recurrence. The HCV RNA level was 84,000,000 copies/mL, and markers for
      other viral causes were not present. The patient became jaundiced and her course
      progressively worsened. She died on day 87 after transplantation. To our
      knowledge, this is the earliest reported case of histological recurrence of HCV
      after LT. It illustrates the importance of older donor and recipient age in the
      same patient as cofactors for early HCV recurrence and poor outcome.

PMID- 17539016
TI  - Tonsil enlargement after liver transplantation in adults--reason enough for
      tonsillectomy? Two cases of tonsillar posttransplantation lymphoproliferative
      disease.
AB  - Posttransplantation lymphoproliferative disease (PTLD) is a well-known
      complication of solid organ and bone marrow transplantation. It is agreed that
      the main causes of PTLD are chronic infection with Epstein-Barr virus (EBV); the
      intensity, rather then the type, of immunosuppression used; and underlying
      recipient disease. Hepatitis C virus (HCV) and cytomegalovirus, as cofactors of
      EBV infection, have been suggested to increase the risk of PTLD. Use of
      calcineurin inhibitors, anti-CD3 monoclonal antibody (OKT3), and antithymocyte
      globulin may increase the risk of PTLD. On the other hand, mycophenolate mofetil,
      sirolimus, and the anti-interleukin-2 receptor monoclonal antibodies Daclizumab
      and basiliximab have not been demonstrated to increase the risk of PTLD. The
      incidence of PTLD after liver transplantation (LT) is estimated to be 1.5-3%, but
      a tonsillar location is extremely rare in adults. Thus, little is known about the
      best diagnostic tools for and treatment by LT recipients with tonsillar PTLD.
      Here, we report 2 cases of adult LT recipients with tonsillar PTLD. Tonsillectomy
      was used as a diagnostic tool and treatment option and resulted in complete
      remission for >2 years. Considering the high mortality and diagnostic
      difficulties of PTLD, together with the relatively low risks of tonsillectomy, we
      recommend tonsillectomy for treating tonsil enlargement of unknown cause and
      suspected PTLD in LT recipients. A larger series of patients and prospective
      studies comparing different treatment options will be needed to substantiate our
      recommendation.

PMID- 17539017
TI  - A case of less than meets the eye.

PMID- 17539019
TI  - Neutrophil depletion protects against murine acetaminophen hepatotoxicity:
      another perspective.

PMID- 17539021
TI  - Treatment of Wilms tumor relapsing after initial treatment with vincristine,
      actinomycin D, and doxorubicin. A report from the National Wilms Tumor Study
      Group.
AB  - OBJECTIVE: We evaluated the use of alternating cycles of
      cyclophosphamide/etoposide and carboplatin/etoposide in children entered on
      National Wilms Tumor Study (NWTS)-5 who were diagnosed between August 1, 1995 and
      May 31, 2002 and who relapsed after chemotherapy with vincristine, actinomycin D,
      and doxorubicin (VAD) and radiation therapy (DD-4A). PATIENTS AND METHODS: One
      hundred three patients who relapsed or had progressive disease after initial VAD
      chemotherapy and radiation therapy were registered on stratum C of the NWTS-5
      Relapse protocol. Twelve patients were not evaluable: five due to insufficient
      data, six due to major protocol violations, and one for refusal of therapy. Among
      the 91 remaining patients, 14 with stage V Wilms tumor (WT), 1 with contralateral
      relapse, and 16 who did not achieve a complete response (CR) to the initial three
      drug chemotherapy were not included in this analysis. Relapse treatment included
      alternating courses of the drug pairs cyclophosphamide/etoposide and
      carboplatin/etoposide, surgery, and radiation therapy. RESULTS: The outcomes of
      60 patients were analyzed. The lung was the only site of relapse for 33 patients;
      other sites of relapse included the operative bed, the abdomen, and liver. Four
      year event-free survival (EFS) and overall survival (OS) were 42.3 and 48.0%
      respectively for all patients and were 48.9 and 52.8% for those who relapsed in
      the lungs only. Thrombocytopenia was the most frequent toxicity. CONCLUSION:
      These results demonstrate that approximately one-half of children with unilateral
      WT who relapse after initial treatment with VAD and radiation therapy can be
      successfully retreated.

PMID- 17539022
TI  - A constitutional balanced t(3;8)(p14;q24.1) translocation results in disruption
      of the TRC8 gene and predisposition to clear cell renal cell carcinoma.
AB  - Studying the molecular basis of familial renal cell carcinoma (RCC) has allowed
      identification of novel RCC genes involved in the pathogenesis of both inherited
      and sporadic RCC. We describe a constitutional balanced t(3;8)(p14;q24.1)
      translocation found in a brother and sister with bilateral clear cell RCC (CC
      RCC) diagnosed in their forties. Consistent with a prior report, we demonstrated
      by RT-PCR of RNA from lymphoblastoid cells fusion mRNAs derived from the fragile
      histidine triad (FHIT) at 3p14 and TRC8 at 8q24.1 in both affected siblings.
      Cytogenetic analysis of a CC-RCC tumor from the affected sister from short-term
      tumor cell culture showed both diploid and pseudotetraploid populations
      containing the translocation and normal appearing chromosomes 3 and 8.
      Fluorescent in situ hybridization using bacterial artificial chromosomes
      containing sequences from the FHIT and TRC8 genes demonstrated normal FHIT
      signals and TRC8 signals on nontranslocated chromosomes in the constitutional
      blood sample, but the TRC8 signal was absent in a subset of diploid and
      pseudotetraploid cells from the tumor. The tumor also contained a heterozygous
      VHL frameshift somatic mutation. These results confirm that balanced
      translocations disrupting the TRC8 and FHIT genes result in an increased genetic
      susceptibility for bilateral CC-RCC. The presence of diploid and tetraploid tumor
      cells with and without TRC8 deletions on the nontranslocated chromosome suggest
      that loss of the remaining normal allele of TRC8 may contribute to tumor
      development at later stages.

PMID- 17539023
TI  - Impairment of microglial responses to facial nerve axotomy in cathepsin S
      deficient mice.
AB  - Cathepsin S (CS) is a lysosomal/endosomal cysteine protease especially expressed
      in cells of a mononuclear lineage including microglia. To better understand the
      role of CS in microglia, we investigated microglial responses after a facial
      nerve axotomy in CS-deficient (CS-/-) and wild-type mice. Microglia in both
      groups accumulated in the facial motor nucleus following axotomy. However, the
      mean number of microglia in CS-/- mice on the axotomized side was significantly
      smaller than that in wild-type mice. Microglia were found to adhere to injured
      motoneurons in wild-type mice, whereas microglia abutted on injured motoneurons
      without spreading on their surface in CS-/- mice. At the same time, the axotomy
      induced down-regulation of tenasin-R, an antiadhesive perineuronal net for
      microglia, was partially abrogated in CS-/- mice. Primary cultured microglia
      prepared from CS-/- mice showed that CS deficiency caused significant suppression
      of migration and transmigration of microglia. In CS-/- mice, impaired
      recruitments of circulating monocytes and T lymphocytes and reduced expression of
      the class II major compatibility complex on the axotomized side were observed.
      Interestingly, cathepsin B, a typical lysosomal cysteine protease, was markedly
      expressed on the axotomized side in CS-/- but not in wild-type microglia.
      Finally, we compared axotomy-induced neuronal death in the two groups and found
      that the percentage of motoneurons that survived in CS-/- mice was significantly
      smaller than that in wild-type mice. The present study strongly suggests that CS
      plays a role in the migration and activation of microglia to protect facial
      motoneurons against axotomy-induced injury.

PMID- 17539024
TI  - Hepatitis B x antigen up-regulates vascular endothelial growth factor receptor 3
      in hepatocarcinogenesis.
AB  - Hepatitis B x antigen (HBxAg) is a trans-activating protein that contributes to
      liver cancer, in part, by altering the expression of cellular genes. However, few
      natural effectors of HBxAg have been identified. Hence, HBxAg positive and
      negative HepG2 cells were prepared and analyzed by PCR select cDNA subtraction.
      The results identified elevated vascular endothelial growth factor receptor-3
      short form splice variant (VEGFR-3(S)) expression in HBxAg positive compared to
      negative cells. Normally, VEGFR-3 activates Akt signaling in lymphatic
      endothelial cells, resulting in lymphangiogenesis. In contrast, the results here
      show that the expression of VEGFR-3(S) is up-regulated in >75% of HBxAg positive
      hepatocellular carcinoma (HCC) nodules. VEGFR-3(S) up-regulation correlates with
      the expression of HBxAg, is associated with decreased survival in tumor bearing
      patients, and when over-expressed in HepG2 cells, strongly stimulated cell growth
      in culture, in soft agar, and accelerated tumor formation in a ligand independent
      manner. VEGFR-3(S) siRNA partially blocked the ability of HBxAg to promote
      hepatocellular growth. In conclusion, HBxAg may short circuit VEGFR-3(S)
      signaling in liver cancer. Blocking VEGFR-3(S) signaling may be effective in
      preventing tumor development and/or prolonging survival in tumor bearing
      patients.

PMID- 17539025
TI  - Hepatitis B viral load predicts survival of HCC patients undergoing systemic
      chemotherapy.
AB  - HCC is a common cause of morbidity and mortality. For patients who are not
      candidates for curative surgery, systemic chemotherapy is one of the standard
      treatments. In parts of China and the Far East, over 80% of HCC patients have
      chronic HBV infection. In this study, we aimed to assess the relationship between
      pre-chemotherapy HBV viral load and the survival of HCC patients. HBV infection
      status was determined prior to chemotherapy in 188 patients, 170 of whom had
      evidence of HBV chronic infection/exposure (160 hepatitis B surface antigen
      [HBsAg]-positive, 10 HBsAg-negative/hepatitis B core antibody-positive). Of
      these, 125 had pretreatment HBV DNA levels determined via real-time PCR.
      Virological data were analyzed using conventional clinical variables to identify
      factors that influenced survival. Multivariate analysis revealed that high total
      bilirubin (P = 0.0016; hazard ratio = 1.040 per 1 muM increase; 95% CI 1.015
      1.065), HCV infection (P = 0.0095; hazard ratio = 6.955; 95% CI 1.606-30.129),
      and high HBV DNA level (P = 0.0217; hazard ratio = 1.650; 95% CI 1.076-2.531)
      affected survival significantly. Exploratory analysis revealed that high levels
      of pretreatment HBV DNA had a significantly higher incidence of severe hepatitis
      during chemotherapy. CONCLUSION: For HCC patients with HBV chronic
      infection/exposure, a high viral load prior to treatment is an adverse factor for
      survival and may be associated with a higher incidence of severe hepatitis during
      chemotherapy. Future strategies to improve the prognosis of HCC patients
      undergoing chemotherapy should consider supportive therapy that incorporates
      antiviral therapies to reduce HBV viral load.

PMID- 17539026
TI  - Integrative database management for mouse development: systems and concepts.
AB  - Cells in the developing embryo must integrate complex signals from the genome and
      environment to make decisions about their behavior or fate. The ability to
      understand the fundamental biology of the decision-making process, and how these
      decisions may go awry during abnormal development, requires a systems biology
      paradigm. Presently, the ability to build models with predictive capability in
      birth defects research is constrained by an incomplete understanding of the
      fundamental parameters underlying embryonic susceptibility, sensitivity, and
      vulnerability. Key developmental milestones must be parameterized in terms of
      system structure and dynamics, the relevant control methods, and the overall
      design logic of metabolic and regulatory networks. High-content data from genome
      based studies provide some comprehensive coverage of these operational processes
      but a key research challenge is data integration. Analysis can be facilitated by
      data management resources and software to reveal the structure and function of
      bionetwork motifs potentially associated with an altered developmental phenotype.
      Borrowing from applied mathematics and artificial intelligence, we conceptualize
      a system that can help address the new challenges posed by the transformation of
      birth defects research into a data-driven science.

PMID- 17539027
TI  - Deviations in gait pattern in experimental models of hindlimb paresis shown by a
      novel pressure mapping system.
AB  - Injuries to the central and peripheral nervous system result in varying degrees
      of paresis and as such alter gait. We developed novel quantitative measures to
      assess compensatory patterns of gait in experimental models of unilateral and
      bilateral hindlimb paresis. We hypothesized that hindlimb paresis results in
      unique alterations in the gait cycle that reflect the symmetry of the initial
      lesion. To test this hypothesis, adult, male Sprague-Dawley rats were subjected
      to a unilateral sciatic nerve crush injury or a moderately severe spinal cord
      contusion injury at T8. Kinematic and timing parameters were captured
      simultaneously in all four limbs and alterations in gait were then compared to
      relevant sham controls. Gait analysis consisted of walking trials through a gait
      tunnel positioned over a Tekscan pressure sensor grid. After sciatic nerve
      injury, animals unweighted the injured limb by shifting their center of mass
      toward the contralateral forelimb and hindlimb. These changes in weight-bearing
      occurred simultaneously with an increase in stance time on the contralateral
      limbs. As might be expected spinal cord injured animals unweighted their
      hindlimbs, as shown by reduced hindlimb contact force and contact pressure. These
      adjustments coincided with a shortening of forelimb stance time and stride
      length. These findings show both alterations and compensatory changes in gait
      that reflect the symmetry of the initial injury.

PMID- 17539029
TI  - Ion- and atom-leaching mechanisms from palladium nanoparticles in cross-coupling
      reactions.
AB  - Leaching of palladium species from Pd nanoparticles under C--C coupling
      conditions was observed for both Heck and Suzuki reactions by using a special
      membrane reactor. The membrane allows the passage of palladium atoms and ions,
      but not of species larger than 5 nm. Three possible mechanistic scenarios for
      palladium leaching were investigated with the aim of identifying the true
      catalytic species. Firstly, we examined whether or not palladium(0) atoms could
      leach from clusters under non-oxidising conditions. By using our membrane
      reactor, we proved that this indeed happens. We then investigated whether or not
      small palladium(0) clusters could in fact be the active catalytic species by
      analysing the reaction composition and the palladium species that diffused
      through the membrane. Neither TEM nor ICP analysis supported this scenario.
      Finally, we tested whether or not palladium(II) ions could be leached in the
      presence of PhI by oxidative addition and the formation of [Pd(II)ArI] complexes.
      Using mass spectrometry, UV-visible spectroscopy and 13C NMR spectroscopy, we
      observed and monitored the formation and diffusion of these complexes, which
      showed that the first and the third mechanistic scenarios were both possible, and
      were likely to occur simultaneously. Based on these findings, we maintain that
      palladium nanoparticles are not the true catalysts in C--C coupling reactions.
      Instead, catalysis is carried out by either palladium(0) atoms or palladium(II)
      ions that leach into solution.

PMID- 17539030
TI  - The emitting state of tryptophan in proteins with highly blue-shifted
      fluorescence.

PMID- 17539031
TI  - Monovalent ion dependence of neomycin B binding to an RNA aptamer characterized
      by spectroscopic methods.
AB  - Understanding the interactions of small molecules like antibiotics with RNA is a
      prerequisite for the development of novel drugs. In this study we address
      structural and thermodynamic features of such interactions by using a simple
      model system: the binding of the highly charged antibiotic neomycin B to a short
      hairpin RNA molecule. Nucleotide A16, which acts as a flap over the neomycin B
      binding pocket, was substituted by the fluorescent adenine analogue 2-aminopurine
      (2-AP). Steady-state and time-resolved fluorescence measurements were
      complemented by UV-melting and circular dichroism studies. The binding of
      neomycin B at three sites was found to have a strong inverse correlation with
      Na(+) concentration. For the highest-affinity site, both fluorescence and UV
      absorption experiments were consistent with a model assuming at least three
      neomycin NH(3) (+) groups participating in addition to hydrogen bonds in
      electrostatic interactions with the RNA. The variation of fluorescence intensity
      and lifetime upon neomycin B binding indicated unstacking of 2-AP16 from
      neighbouring bases as it flipped over the binding pocket. RNA conformational
      changes upon binding of the antibiotic were confirmed by circular dichroism. The
      two weaker binding sites were characterized as unspecific binding to the aptamer,
      while the high-affinity binding event was shown to be highly specific even at
      high ionic concentration. In addition, 2-AP was confirmed to be a noninvasive
      fluorescent probe; it serves as a sensitive spectroscopic tool to investigate
      details of the interactions between small molecules and RNA.

PMID- 17539032
TI  - Organic electronic devices and their functional interfaces.
AB  - A most appealing feature of the development of (opto)electronic devices based on
      conjugated organic materials is the highly visible link between fundamental
      research and technological advances. Improved understanding of organic material
      properties can often instantly be implemented in novel device architectures,
      which results in rapid progress in the performance and functionality of devices.
      An essential ingredient for this success is the strong interdisciplinary nature
      of the field of organic electronics, which brings together experts in chemistry,
      physics, and engineering, thus softening or even removing traditional boundaries
      between the disciplines. Naturally, a thorough comprehension of all properties of
      organic insulators, semiconductors, and conductors is the goal of current
      efforts. Furthermore, interfaces between dissimilar materials-organic/organic and
      organic/inorganic-are inherent in organic electronic devices. It has been
      recognized that these interfaces are a key for device function and efficiency,
      and detailed investigations of interface physics and chemistry are at the focus
      of research. Ultimately, a comprehensive understanding of phenomena at interfaces
      with organic materials will improve the rational design of highly functional
      organic electronic devices.

PMID- 17539033
TI  - Progress in the understanding of drug-receptor interactions, part 2: experimental
      and theoretical electrostatic moments and interaction energies of an angiotensin
      II receptor antagonist (C30H30N6(O)3S).
AB  - A combined experimental and theoretical charge density study of an angiotensin II
      receptor antagonist (1) is presented focusing on electrostatic properties such as
      atomic charges, molecular electric moments up to the fourth rank and energies of
      the intermolecular interactions, to gain an insight into the physical nature of
      the drug-receptor interaction. Electrostatic properties were derived from both
      the experimental electron density (multipole refinement of X-ray data collected
      at T=17 K) and the ab initio wavefunction (single molecule and fully periodic
      calculations at the DFT level). The relevance of SO and SN intramolecular
      interactions on the activity of 1 is highlighted by using both the crystal and
      gas-phase geometries and their electrostatic nature is documented by means of
      QTAIM atomic charges. The derived electrostatic properties are consistent with a
      nearly spherical electron density distribution, characterised by an intermingling
      of electropositive and -negative zones rather than by a unique electrophilic
      region opposed to a nucleophilic area. This makes the first molecular moment
      scarcely significant and ill-determined, whereas the second moment is large,
      significant and highly reliable. A comparison between experimental and
      theoretical components of the third electric moment shows a few discrepancies,
      whereas the agreement for the fourth electric moment is excellent. The most
      favourable intermolecular bond is show to be an NHN hydrogen bond with an energy
      of about 50 kJ mol(-1). Key pharmacophoric features responsible for attractive
      electrostatic interactions include CHX hydrogen bonds. It is shown that methyl
      and methylene groups, known to be essential for the biological activity of the
      drug, provide a significant energetic contribution to the total binding energy.
      Dispersive interactions are important at the thiophene and at both the phenyl
      fragments. The experimental estimates of the electrostatic contribution to the
      intermolecular interaction energies of six molecular pairs, obtained by a new
      model proposed by Spackman, predict the correct relative electrostatic energies
      with no exceptions.

PMID- 17539034
TI  - Synthesis, characterization, and electrochemiluminescence of luminol-reduced gold
      nanoparticles and their application in a hydrogen peroxide sensor.
AB  - It was found that chloroauric acid (HAuCl(4)) could be directly reduced by the
      luminescent reagent luminol in aqueous solution to form gold nanoparticles
      (AuNPs), the size of which depended on the amount of luminol. The morphology and
      surface state of as-prepared AuNPs were characterized by transmission electron
      microscopy, UV/visible spectroscopy, X-ray photoelectron spectroscopy, FTIR
      spectroscopy, and thermogravimetric analysis. All results indicated that residual
      luminol and its oxidation product 3-aminophthalate coexisted on the surface of
      AuNPs through the weak covalent interaction between gold and nitrogen atoms in
      their amino groups. Subsequently, a luminol-capped AuNP-modified electrode was
      fabricated by the immobilization of AuNPs on a gold electrode by virtue of
      cysteine molecules and then immersion in a luminol solution. The modified
      electrode was characterized by cyclic voltammetry, electrochemical impedance
      spectroscopy, and scanning electron microscopy. The as-prepared modified
      electrode exhibited an electrochemiluminescence (ECL) response in alkaline
      aqueous solution under a double-step potential. H2O2 was found to enhance the
      ECL. On this basis, an ECL sensor for the detection of H2O2 was developed. The
      method is simple, fast, and reagent free. It is applicable to the determination
      of H2O2 in the range of 3x10(-7)-1x10(-3) mol L(-1) with a detection limit of
      1x10(-7) mol L(-1) (S/N=3).

PMID- 17539035
TI  - Cycloaddition of CO2 to epoxides catalyzed by polyaniline salts.
AB  - The catalytic activity of polyaniline-HX (X=I, Br, Cl) (PANI-HI, PANI-HBr, PANI
      HCl) for the cycloaddition of CO2 to propylene oxide (PO) to produce propylene
      carbonate (PC) was studied for the first time. It was shown that all the PANI
      salts were active for the reaction, and PANI-HI was most active and selective. On
      the basis of the preliminary results, the effect of the reaction conditions on
      the cycloadditions of CO2 to propylene oxide and epichlorohydrin was further
      investigated by using PANI-HI as the catalyst. The results indicated that the
      optimized temperature was around 115 degrees C. The maxima occurred in yield
      versus pressure curves at about 5 MPa for both substrates. Complete conversion
      was achieved in 3 h for epichlorohydrin and 6 h for propylene oxide at 115
      degrees C and 5 MPa. With propylene oxide as the substrate, the reusability of
      PANI-HI was evaluated and no loss of catalytic activity was detectable after the
      catalyst had been reused five times. The catalyst was characterized by
      thermogravimetric analysis (TGA) and scanning electron microscopy (SEM), which
      provided further evidence for the high stability of the catalyst. We believe that
      the catalyst has great potential for industrial applications because it has some
      unusual advantages, such as its easy preparation, high activity, selectivity,
      stability, low cost, and simple separation from products.

PMID- 17539036
TI  - Mechanisms for the dehydrogenation of alkanes on platinum: insights gained from
      the reactivity of gaseous cluster cations, Ptn + n=1-21.
AB  - Rates for the dihydrogen elimination of methane, ethane, and propane with
      cationic platinum clusters, Pt(n) (+) (1<or=n<or=21), were measured under binary
      collision conditions in a Fourier transform ion cyclotron resonance mass
      spectrometer (FTICR). The reaction rate for a given cluster, Ptn +, follows the
      trend k(CH4)<k (C2H6)<k(C3H8). Methane is particular in the sense that reactivity
      is highly variable; some clusters (n=1-3, 5-9, 11, 12, 15) are very reactive
      towards methane, while all other clusters react with low efficiency or not at
      all. For propane, all clusters react efficiently, while the reactivity of ethane
      lies in-between that of methane and propane. By necessity, dihydrogen elimination
      of methane occurs according to a 1,1-elimination mechanism. Ethane
      dehydrogenation takes place according to both a 1,1- and a 1,2-mechanism. The
      difference between the 1,1- and 1,2-mechanisms is well displayed in specifically
      increased rates for those clusters that were inefficient in the reaction with
      methane, as well as in the observed selectivity for H2, HD, and D2 elimination in
      the reaction with [D3]-1,1,1-ethane. Some twofold dihydrogen elimination is
      observed as well. The outcome of reactions with C2H6 in the presence of D(2)
      demonstrates exchange of all hydrogen atoms in [PtnC2H4]+ with deuterium atoms. A
      potential energy diagram with a high barrier for the second H2 elimination
      summarizes these observations. For propane twofold dihydrogen elimination is
      dominating, and for these reactions a far less regiospecific and more random loss
      of the hydrogens can be inferred, as was demonstrated by the reactions with [D6]
      1,1,1,3,3,3-propane.

PMID- 17539037
TI  - On the application of CZE to the study of protein denaturation.
AB  - Experimental mobilities obtained from CZE are used to study protein denaturation
      through a model based on known physicochemical theories. This model is able to
      provide additional information concerning the folded and unfolded protein states
      from mobility data. Its use comprises first the evaluation of relevant parameters
      of the protein microstates like the electrostatic free energy, apart from the
      classical conformational free energy, and second the expression of raw
      experimental data concerning the folding-unfolding transition into more specific
      physicochemical parameters like protein hydrodynamic radius, net charge number,
      and hydration. Spurious effects that are intrinsic to the experimental evaluation
      of the mobility of protein states, like BGE viscosity, pH, and ionic strength
      variations accompanying the changes of the denaturant agent intensity are
      eliminated. In order to illustrate the proposal of this work, two case studies
      are considered here. The first one concerns thermal and urea denaturations of
      horse heart ferricytochrome c and the second one involves thermal denaturation of
      hen egg-white lysozyme. Thus, relevant theoretical thermodynamic considerations
      of the folded-unfolded protein transition are presented, where the electrostatic
      free energy is included explicitly in the effective free energy. It is found that
      this transition involves sharp increases of hydrodynamic radius and protein
      hydration.

PMID- 17539038
TI  - Iron protoporphyrin-modified monolithic support for on-line preconcentration of
      angiotensin prior to CE analysis.
AB  - An on-line preconcentration method using a polymeric monolithic support is
      proposed for the retention of the decapeptide angiotensin I and its subsequent
      analysis by CZE. Monolithic capillary columns were prepared in fused-silica (FS)
      capillaries of 150 microm id by ionizing radiation-initiated in situ
      polymerization and cross-linking of diethylene glycol dimethacrylate and glycidyl
      methacrylate, and chemically modified with iron protoporphyrin IX (Fe-ProP).
      Monolithic microcolumns (8 mm long) were coupled on-line to the inlet of the
      separation capillary (FS capillary, 75 microm id x10 cm from the inlet to the
      microcolumn and 27 cm from the microcolumn to the detector). Angiotensin I was
      released from the sorbent by a 50 mM sodium phosphate, pH 2.5/ACN, 75:25 v/v
      solution and then analyzed by CZE with UV absorption detection at 214 nm. The
      concentration LOQ (CLOQ) was 0.5 ng/mL. The Fe-ProP-derivatized monolithic
      microcolumn coupled to the separation capillary exhibited a high retention
      capacity for peptide angiotensin I, and showed as much as 10,000-fold improvement
      in concentration sensitivity.

PMID- 17539039
TI  - Highly specific enrichment of phosphopeptides by zirconium dioxide nanoparticles
      for phosphoproteome analysis.
AB  - Large-scale characterization of phosphoproteins requires highly specific methods
      for the purification of phosphopeptides because of the low abundance of
      phosphoproteins and substoichiometry of phosphorylation. A phosphopeptide
      enrichment method using ZrO2 nanoparticles is presented. The high specificity of
      this approach was demonstrated by the isolation of phosphopeptides from the
      digests of model phosphoproteins. The strong affinity of ZrO2 nanoparticles to
      phosphopeptides enables the specific enrichment of phosphopeptides from a complex
      peptide mixture in which the abundance of phosphopeptides is two orders of
      magnitude lower than that of nonphosphopeptides. Superior selectivity of ZrO2
      nanoparticles for the enrichment of phosphorylated peptides than that of
      conventional immobilized metal affinity chromatography was observed. Femtomole
      phosphopeptides from digestion products could be enriched by ZrO2 nanoparticles
      and can be well detected by MALDI mass spectrometric analysis. ZrO2 nanoparticles
      were further applied to selectively isolate phosphopeptides from the tryptic
      digestion of mouse liver lysate for phosphoproteome analysis by nanoliter LC
      MS/MS (nano-LC-MS/MS) and MS/MS/MS. A total of 248 defining phosphorylation sites
      and 140 phosphorylated peptides were identified by manual validation using a
      series of rigid criteria.

PMID- 17539040
TI  - Reproducible protein analysis by CE using linear polyacrylamide-coated
      capillaries and hydrochloric acid rinsing.
AB  - Hydrochloric acid was investigated as a rinsing reagent to remove adsorbed
      proteins from linear polyacrylamide-coated capillaries for electrophoresis. Three
      model proteins were used, namely cytochrome c as a basic protein, beta
      lactoglobulin as an acidic protein, and beta-casein as a more easily denaturing
      protein. In order to regenerate capillary surfaces, they have been rinsed for 5
      min with 2 M hydrochloric acid, 5 min with water, and then 30 min with buffer
      after every tenth run. It was found important to perform this regeneration
      procedure on time. The obtained results show good repeatability of the apparent
      EOF mobility with percentage RSDs below 3% (n = 60) in various cases. These good
      results were mainly confirmed in long-term series with more than 200 runs each.
      Only very high concentrations (175 microM) of beta-lactoglobulin and beta-casein
      at pH 3.5 gave RSD% values above 5%. For these conditions, the further test of
      85% m/m phosphoric acid as rinsing reagent showed a good repeatability of the
      apparent EOF mobilities as well.

PMID- 17539041
TI  - Low-temperature facile template synthesis of crystalline inorganic composite
      hollow spheres.
AB  - This report presents a facile approach for the low-temperature synthesis of
      crystalline inorganic-oxide composite hollow spheres by employing the bulk
      controlled synthesis of inorganic-oxide nanocrystals with polymer spheres as
      templates. The sulfonated polystyrene gel layer can adsorb the target precursor
      and induce inorganic nanocrystals to grow on the template in situ. The
      crystalline phase and morphology of the composite shell is tunable. By simply
      adjusting the acidity of the titania sol, crystalline titania composite hollow
      spheres with tunable crystalline phases of anatase, rutile, or a mixture of both
      were achieved. The approach is general and has been extended to synthesize the
      representative perovskite oxide (barium and strontium titanate) composite hollow
      spheres. The traditional thermal treatment for crystallite transformation is not
      required, thus intact shells can be guaranteed. The combination of oxide
      properties such as high refractive index, high dielectric constant, and catalytic
      ability with the cavity of the hollow spheres is promising for applications such
      as opacifiers, photonic crystals, high-kappa-gate dielectrics, and
      photocatalysis.

PMID- 17539042
TI  - Regioselective borylation of porphyrins by C-H bond activation under iridium
      catalysis to afford useful building blocks for porphyrin assemblies.
AB  - Highly regioselective and efficient borylation of a variety of porphyrins has
      been achieved by reaction with bis(pinacolato)diboron through C-H bond activation
      under iridium catalysis on the basis of the synthetic protocol developed by
      Miyaura, Hartwig, and Smith. A boryl group can be selectively introduced at
      sterically uncongested positions in the peripheral aryl groups of porphyrin
      substrates whose peripheral beta-positions are sterically hindered. Curiously,
      beta substituents adjacent to the aryl group to be borylated have unexpectedly
      large effects on the regioselectivity, because the iridium catalyst can
      discriminate between subtle steric differences. Chemoselective borylation was
      also achieved for several functionalized porphyrins. This borylation protocol can
      be applied to various monomeric and oligomeric functional porphyrins, hence
      offering an efficient route to elaborate multiporphyrin-based molecular
      constructs.

PMID- 17539043
TI  - Improving fragmentation of poorly fragmenting peptides and phosphopeptides during
      collision-induced dissociation by malondialdehyde modification of arginine
      residues.
AB  - Despite significant technological and methodological advancements in peptide
      sequencing by mass spectrometry, analyzing peptides that exhibit only poor
      fragmentation upon collision-induced dissociation (CID) remains a challenge. A
      major cause for unfavorable fragmentation is insufficient proton 'mobility' due
      to charge localization at strongly basic sites, in particular, the guanidine
      group of arginine. We have recently demonstrated that the conversion of the
      guanidine group of the arginine side chain by malondialdehyde (MDA) is a
      convenient tool to reduce the basicity of arginine residues and can have
      beneficial effects for peptide fragmentation. In the present work, we have
      focused on peptides that typically yield incomplete sequence information in CID
      MS/MS experiments. Energy-resolved tandem MS experiments were carried out on
      angiotensins and arginine-containing phosphopeptides to study in detail the
      influence of the modification step on the fragmentation process. MDA modification
      dramatically improved the fragmentation behavior of peptides that exhibited only
      one or two dominant cleavages in their unmodified form. Neutral loss of
      phosphoric acid from phosphopeptides carrying phosphoserine and threonine
      residues was significantly reduced in favor of a higher abundance of fragment
      ions. Complementary experiments were carried out on three different instrumental
      platforms (triple-quadrupole, 3D ion trap, quadrupole-linear ion trap hybrid) to
      ascertain that the observation is a general effect.

PMID- 17539044
TI  - Sequential evaluation of a medical diagnostic test with binary outcomes.
AB  - In a study evaluating a medical diagnostic test, human samples are valuable and
      often costly, therefore prime concerns require termination of the study if the
      test is evidently inefficient (or efficient) in diagnosis of diseases in order to
      keep the number of samples as low as possible. In this paper, we propose
      sequential designs to evaluate the sensitivity and specificity of a diagnostic
      test. One method allows early stopping if the sensitivity and specificity of a
      new medical test are both within the level of tolerance. Another method
      terminates the study if either the sensitivity or the specificity is below the
      minimally acceptable level. The latter method minimizes the expected sample size
      when the test does not meet expectations on performance, and illustrates
      substantial advantage of having smaller expected sample sizes in various two
      stage designs compared to the sample sizes of single-stage designs when a
      diagnostic test is not promising.

PMID- 17539045
TI  - Vitamin D: deficiency or no deficiency?

PMID- 17539046
TI  - Phytophotodermatitis due to puncture from lime tree thorn.

PMID- 17539047
TI  - The difference between state public health veterinarians and state veterinarians.

PMID- 17539048
TI  - Current awareness on yeast.

PMID- 17539049
TI  - The effects of insurance on the medical profession.

PMID- 17539050
TI  - Dengue and dengue hemorrhagic fever.

PMID- 17539051
TI  - Trials and tribulations.

PMID- 17539052
TI  - Cancer vaccines on the horizon.

PMID- 17539054
TI  - An audience with... Darren Carroll. Interview by Joanna Owens.

PMID- 17539053
TI  - Where now for new drugs for atherosclerosis?

PMID- 17539055
TI  - Therapies for Alzheimer's disease.

PMID- 17539056
TI  - Lisdexamfetamine dimesylate.

PMID- 17539057
TI  - The evolution of life-sciences sales.

PMID- 17539058
TI  - Earth network.

PMID- 17539059
TI  - Time 100 scientists & thinkers. Paul Allen.

PMID- 17539060
TI  - Time 100 scientists & thinkers. Steven Nissen.

PMID- 17539061
TI  - Time 100 scientists & thinkers. Kari Stefannson.

PMID- 17539066
TI  - Look, Ma, cavities!

PMID- 17539067
TI  - Perspective on PCBs.

PMID- 17539068
TI  - Embryonic mortality and chromosomal alterations caused by aroclor 1254 in ring
      doves.

PMID- 17539069
TI  - Toxicology of PCBs for Mammals and for Birds.

PMID- 17539070
TI  - Epidemiologic study on Yusho, a Poisoning Caused by Ingestion of Rice Oil
      Contaminated with a Commercial Brand of Polychlorinated Biphenyls.

PMID- 17539071
TI  - Chlorinated aromatic hydrocarbon induced modifications of the hepatic endoplasmic
      reticulum: concentric membrane arrays.

PMID- 17539072
TI  - Biological effects of polychlorinated biphenyls in rats and quail.

PMID- 17539074
TI  - PCBs and Interactions with Insecticides.

PMID- 17539073
TI  - Photochemical Degradation of Chloro-biphenyls (PCBs).

PMID- 17539075
TI  - Polychlorinated biphenyl interactions with tissue culture cells.

PMID- 17539076
TI  - Toxicities of PCBs to Fish and Environmental Residues.

PMID- 17539077
TI  - The sensitivity of fish ATPases to polychlorinated biphenyls.

PMID- 17539078
TI  - Studies on the Mechanism of Toxicity of DDT and Polychlorinated Biphenyls:
      Disruption of Osmoregulation in Marine Fish.

PMID- 17539080
TI  - The PCB Situation in Germany.

PMID- 17539079
TI  - Polychlorinated Biphenyls (Aroclor 1242): Effects of Uptake on E. coli Growth.

PMID- 17539081
TI  - Comments on research needs.

PMID- 17539083
TI  - Some Chemical Aspects of Polychlorinated Biphenyls (PCBs).

PMID- 17539082
TI  - Rates and Routes of Transport of PCBs in the Environment.

PMID- 17539084
TI  - Accumulation of polychlorinated biphenyls in ecosystems.

PMID- 17539085
TI  - Contamination of the Bay of Fundy-Gulf of Maine area with Polychlorinated
      Biphenyls, Polychlorinated Terphenyls, Chlorinated Dibenzodioxins, and
      Dibenzofurans.

PMID- 17539086
TI  - Recent Fluctuations of Chlorobiphenyls (PCBs) in the Green Bay, Wisconsin,
      Region.

PMID- 17539087
TI  - Polychlorinated biphenyl residues in milk of environmentally and experimentally
      contaminated cows.

PMID- 17539088
TI  - Polychlorinated Biphenyls in Non-carbon Copy Paper.

PMID- 17539089
TI  - PCB and the Paper Industry-A Progress Report.

PMID- 17539090
TI  - Levels of polychlorinated biphenyls in foods in sweden.

PMID- 17539091
TI  - Occurrence of polychlorinated biphenyls in humans.

PMID- 17539092
TI  - Levels of polychlorinated biphenyls in adipose tissue of the general population
      of the nation.

PMID- 17539093
TI  - Polychlorinated biphenyls residues in the plasma and hair of refuse workers.

PMID- 17539094
TI  - Food exposures to polychlorinated biphenyls.

PMID- 17539095
TI  - Polychlorinated biphenyls: their effects on penned pheasants.

PMID- 17539096
TI  - Heavy metals in the environment: an overview.

PMID- 17539098
TI  - Perspective on low level lead toxicity.

PMID- 17539097
TI  - Perspective on CHLORINATED DIBENZODIOXINS And DIBENZOFURANS.

PMID- 17539099
TI  - Overview: conference on occupational and environmental reproductive hazards.

PMID- 17539100
TI  - Health effects of electric and magnetic fields: overview of research
      recommendations.
AB  - We developed a series of articles concerning epidemiologic research on potential
      health effects of electric and magnetic fields. Our goal was to identify
      methodological issues that have arisen through past studies of cancer,
      reproduction, and neurobehavioral outcomes in order to suggest strategies to
      extend knowledge. Following an overview of relevant physics and engineering
      principles, cancer epidemiology of electric and magnetic fields is discussed
      separately with a focus on epidemiologic methods and cancer biology,
      respectively. Reproductive health studies, many of which focus on exposure from
      video display terminals are then summarized, followed by an evaluation of the
      limited literature on neurobehavioral outcomes, including suicide and depression.
      Methodological issues in exposure assessment are discussed, focusing on the
      challenges in residential exposure assessment and interpretation of wire
      configuration codes. An overview offers recommendations for priorities across
      these topic areas, emphasizing the importance of resolving the question of wire
      codes and childhood cancer. Collectively, these articles provide an array of
      observations and suggestions regarding the epidemiologic literature, recognizing
      the potential benefits to science and public policy.

PMID- 17539101
TI  - Cell Proliferation and Chemical Carcinogenesis: summary and future directions.

PMID- 17539102
TI  - Cell proliferation: concluding remarks.

PMID- 17539104
TI  - Source for MCS Facts.

PMID- 17539103
TI  - Conclusion: challenges for the future.
AB  - The title "Challenges for the Future" implies the challenge to summarize a very
      complex meeting. Of necessity, I will present a personal impression. My interest
      is in risk assessment, which I define as a process for summarizing science in
      support of decision making. Risk assessment is sometimes regarded as arcane
      numerology, a rigid process of computing risk numbers in which much available
      science is unused. I am a strong advocate for the broader definition of risk
      assessment. It is encouraging to learn how much science is becoming available for
      use in risk assessment for gasoline, its components, and alternative fuels.

PMID- 17539105
TI  - Don'T ban chlorine-use it wisely.

PMID- 17539106
TI  - Litigation-related Research.

PMID- 17539107
TI  - Faulty conclusions.

PMID- 17539109
TI  - Radon risks.

PMID- 17539108
TI  - Statement from the Work Session on Environmentally induced Alterations in
      Development: A Focus on Wildlife.

PMID- 17539110
TI  - The right to know is for everyone.

PMID- 17539111
TI  - Exposure Now Sickness Later Early Exposure to PCBs and Dioxins May Increase Some
      Childhood Diseases.

PMID- 17539112
TI  - Home sick does living near a pesticide factory threaten the immune system?

PMID- 17539113
TI  - Smoking Gun Other Risk Factors Ruled Out for Women Exposed to ETS.

PMID- 17539114
TI  - Proportional mortality among vinyl chloride workers.
AB  - In a proportional mortality analysis of 161 deceased workers in two plants
      processing or producing vinyl chloride, a 50% excess of deaths due to all cancer
      was seen. Specific sites of cancer with the greatest excess included liver and
      biliary tract, lung and brain. The excess in fatal cancer was seen mainly in men
      who died before age 60. Also, there was a trend in time in the ratio of observed
      to expected deaths: since 1970 over twice as many cancer deaths as expected have
      occurred.

PMID- 17539115
TI  - Heavy metals in the environment. III: Overview.

PMID- 17539117
TI  - Remarks to opening session.

PMID- 17539116
TI  - Target organ toxicity: liver and kidney.

PMID- 17539118
TI  - Office of associate director for interagency programs: summary statement.

PMID- 17539119
TI  - Office of the associate director for extramural program: summary statement.

PMID- 17539120
TI  - Office of health hazard assessment: summary statement.

PMID- 17539122
TI  - Office of the scientific director: summary statement.

PMID- 17539121
TI  - Office of the associate director for genetics: summary statement.

PMID- 17539123
TI  - Laboratory of pharmacology: summary statement.

PMID- 17539124
TI  - Laboratory of environmental biophysics: summary statement.

PMID- 17539125
TI  - Environmental biophysics branch; summary statement.

PMID- 17539126
TI  - Laboratory of environmental mutagenesis: summary statement.

PMID- 17539127
TI  - Laboratory of environmental mutagenesis: summary statement.

PMID- 17539128
TI  - Laboratory of environmental toxicology: summary statement.

PMID- 17539129
TI  - Biometry branch: summary statement.

PMID- 17539130
TI  - Research services branch: summary statement.

PMID- 17539131
TI  - Environmental biology and chemistry branch: summary statement.

PMID- 17539133
TI  - Air pollution and cancer-risk assessment methodology and epidemiological
      evidence: A preface.

PMID- 17539134
TI  - Comparative female reproductive tract development and morphology.
AB  - A brief description of the basic pattern of mammalian organogenesis of the female
      reproductive tract is presented based on events as they occur in human beings.
      The emphasis is not on the details of this development, but rather its
      organization and timing. Tables of comparative development provide a comparison
      of similar events between man, rat, mouse, and chick.

PMID- 17539135
TI  - Induction of dominant mutations that cause skeletal malformations in mice.
AB  - A new approach for estimating genetic risk to humans from radiation is based upon
      an analysis of the frequency of induction of dominant mutations that cause
      skeletal abnormalities in mice. The main goal of this work is to improve
      estimates of the effect that an increase in the mutation frequency would have
      upon the incidence of serious genetic diseases in humans. The data obtained
      relate to dominant and irregularly inherited conditions in humans, which together
      constitute the great majority of human genetic diseases. The skeletal method
      could be used in chemical mutagenesis research in order to make a much more
      accurate risk-benefit analysis. A more likely application, however, is to provide
      a relatively quick and easy mammalian testing procedure for identifying mutagens.
      Dominant mutations at an unknown, but probably large, number of genetic loci
      could be detected. The relatively quick and easy procedure, which is described,
      has not yet been tested.

PMID- 17539136
TI  - Alteractions of germ cells leading to mutagenesis and their detection.
AB  - Germ cell risk is an essential component of estimating the deleterious results of
      environmental mutagens. The present set of in vivo model systems appears to have
      limited ability to measure germ cell risk from all types of genetic lesions. The
      assays most practical for use in genetic testing measure the induction of
      chromosome alterations but not specific locus gene mutations. Quantitative
      estimation of germ cell risk based on such available assays is difficult to make
      and may lead to incorrect assumptions of risk. Better assessment of germ cell
      genetic damage will require expansion of present procedures to increase
      sensitivity and the development of improved assay systems.

PMID- 17539137
TI  - Basic mechanisms of ovarian function: germ cells.
AB  - Recent work is reviewed on several molecular aspects of gene expression during
      oocyte maturation and early development. Several analyses have been carried out
      on protein synthesis patterns using the high resolution two-dimensional
      polyacrylamide gel electrophoresis technique. The protein pattern of some 400-500
      spots in sea urchin oocytes before and just after fertilization are quite
      similar. By gastrula, major stage specific protein changes have been noted. In a
      similar study major protein changes are noted during the meiotic maturation
      process in mammals. With the use of the single-copy DNA hybridization technique,
      the quantitative levels of rare mRNA sequence expression have been determined
      during oogenesis and early development in the sea urchin model. The mature oocyte
      sequence set of some 37 x 10(6) nucleotides of information (or potentially 18,500
      different proteins) is synthesized during oogenesis and slowly utilized during
      development. The sea urchin gastrula mRNA is predominantly synthesized by the
      embryo genome; however, essentially all those gastrula mRNA sequences can also be
      found in the mature oocyte (maternal) set. It is proposed by Hough-Evans et al.
      that this maternal sequence set, which is made during oogenesis and both utilized
      (translated in 10,000-20,000 proteins), and in part, continually synthesized by
      all stages of the embryo, plays a critical role in the morphogenic formation of a
      sea urchin embryo.

PMID- 17539138
TI  - Somatic cells as indicators of germinal mutations in the mouse.
AB  - In attempts to find a prescreen for mutagens that may induce heritable mutations
      in mammals, an in vivo somatic mutation test has been developed in the mouse that
      uses a localized gene product (hair pigment), is relatively fast and cheap, and
      gives results that have some predictive value for point mutation induction in
      spermatogonia. Embryos heterozygous at specific coat color loci are exposed to
      the presumptive mutagen, and 3 weeks later the fur is observed for spots of
      altered color. It is possible to distinguish spots resulting from expression of
      the recessive (RS's) from spots having various other causes.In tests with seven
      compounds, mutation rates per locus and unit dose have been calculated on the
      assumption that 175 cells are at risk per 10(1/4)-day embryo (a number derived
      from distribution of spot proportions). These rates are found to be roughly
      parallel to, but uniformly higher than spermatogonial point-mutation rates for
      the same seven compounds. The higher somatic rates are presumably due to the fact
      that RS's can result from several genetic mechanisms besides point mutations. The
      spot test, which has not to date given any false negatives, may thus be
      considered a useful in vivo prescreen for heritable germinal mutations in
      mammals.

PMID- 17539139
TI  - Factors influencing reproduction and genetic toxic effects on male gonads.
AB  - The objective of toxicological study of a target organ, such as the testis, is to
      elucidate the qualitative and quantitative toxic effects of a chemical on that
      organ. The ultimate objective is to assess the toxic effects of a chemical in
      laboratory animals and extrapolate the pertinent experimental data to man. To
      accomplish these objectives, one must consider the main factors which may
      influence and modulate the toxic effects of chemicals in the organ. In the male
      gonads, such modifying factors are the pharmacokinetic parameters governing the
      absorption, distribution, activation and detoxification of indirect carcinogens,
      covalent bindings to macromolecules, and DNA damage as well as DNA repair of
      damaged germ cells. All of these factors have been presently studied in our
      laboratory and are discussed in this paper with the exception of covalent
      bindings to macromolecules.The pharmacokinetic studies demonstrated that the
      functional blood-testis barrier (BTB) closely resembles the blood-brain barrier
      in transport characteristics: the permeability of nonelectrolytes and the acidic
      drugs with pK(a) values depend upon their molecular size and their partition
      coefficients, respectively. Thus, the functional BTB, restricts the permeability
      of many foreign compounds to male germ cells. Studies of mixed function oxidases
      and cytochrome P-450 system in male gonads demonstrated that the presence of AHH,
      EH, and GSH-ST implicate activation and detoxification of polycyclic
      hydrocarbons. Thus, active electrophiles may exert significant toxic effects
      locally within both interstitial and germ cell compartments. The presence of an
      efficient DNA repair system in premeiotic spermatogenic cells (and not in
      spermiogenic cells) can further modify both toxic and mutagenic events in the
      subsequent differentiation of germ cells to mature spermatozoa.

PMID- 17539140
TI  - Introduction.

PMID- 17539141
TI  - Chemistry of PCBs and PBBs.

PMID- 17539142
TI  - Metabolism and biochemical toxicity of PCBs and PBBs.

PMID- 17539143
TI  - Human exposure to polychorinated biphenyls and polybrominated biphenyls.

PMID- 17539144
TI  - Clinical infertility in women.
AB  - Fertility results from coordinate functioning of components of the hypothalamic
      pituitary-ovarian-genital axis. In normal women, ovarian sex steroid hormones act
      as the mediators of these interactions.Infertility is a clinical manifestation of
      the failure of one or more of the components to function appropriately.
      Determining the locus of dysfunction provides the basis for rational treatment.
      For these purposes, both direct measurement of serum hormone levels and
      assessments of target organ function are utilized.

PMID- 17539146
TI  - General recommendations.

PMID- 17539145
TI  - Animal toxicology.

PMID- 17539147
TI  - General summary and conslusions.

PMID- 17539148
TI  - Environmental fate of five radio-labeled coal conversion by-products evaluated in
      a laboratory model ecosystem.
AB  - Anthracene, fluorene, carbazole, dibenzofuran, and dibenzothiophene are five
      typical by-products of coal conversion which are likely to be environmental
      pollutants. These were radiolabeled to high specific activity and purity by
      simple tritium exchange and evaluated for environmental fate in laboratory model
      ecosystems. Anthracene and fluorene were biologically converted to hydroxy and
      keto analogs. Carbazole was N-methylated and N-acetylated. Dibenzothiophene was
      microsomally oxidized to the sulfoxide and sulfone. Dibenzofuran was relatively
      inert to biodegradation. The octanol/water partition coefficient for the parent
      compounds was well correlated with ecological magnification indicating the
      possibility of predicting environmental behavior from physicochemical parameters.

PMID- 17539149
TI  - Environmental health sciences center task force review on halogenated organics in
      drinking water.
AB  - The disinfection of drinking water by chlorination has in recent years come under
      closer scrutiny because of the potential hazards associated with the production
      of stable chlorinated organic chemicals. Organic chemical contaminants are common
      to all water supplies and it is now well-established that chlorinated by-products
      are obtained under conditions of disinfection, or during tertiary treatment of
      sewage whose products can ultimately find their way into drinking water supplies.
      Naturally occurring humic substances which are invariably present in drinking
      waters are probably the source of chloroform and other halogenated methanes, and
      chloroform has shown up in every water supply investigated thus far.The
      Environmental Protection Agency is charged with the responsibility of assessing
      the public health effects resulting from the consumption of contaminated drinking
      water. It has specifically undertaken the task of determining whether organic
      contaminants or their chlorinated derivatives have a special impact, and if so,
      what alternatives there are to protect the consumer against bacterial and viral
      diseases that are transmitted through infected drinking waters. The impetus to
      look at these chemicals is not entirely without some prima facie evidence of
      potential trouble. Epidemiological studies suggested a higher incidence of cancer
      along the lower Mississippi River where the contamination from organic chemicals
      is particularly high. The conclusions from these studies have, to be sure, not
      gone unchallenged.The task of assessing the effects of chemicals in the drinking
      water is a difficult one. It includes many variables, including differences in
      water supplies and the temporal relationship between contamination and
      consumption of the finished product. It must also take into account the relative
      importance of the effects from these chemicals in comparison to those from
      occupational exposure, ingestion of contaminated foods, inhalation of polluted
      air, and many others. The susceptibility of different age, genetic, and ethnic
      groups within the population must also be carefully considered. The present
      review discusses: the reasons for disinfection; the general occurrence of
      chlorinated organics in drinking water; the chemistry in the synthesis of
      chlorinated organics under aqueous conditions; and alternatives to chlorine for
      disinfection.

PMID- 17539150
TI  - Penetration of chemicals into the oocyte, uterine fluid, and preimplantation
      blastocyst.
AB  - Chemicals, including commonly used drugs (e.g., penicillin, meprobamate,
      pyridium, and mercaptomerin) penetrate and persist for some time in the ovarian
      follicular fluid at concentrations approximately similar to that of the serum.
      Information as to the penetration of chemicals into the granulosa cells and into
      the oocyte is scanty, although there are some indications that these structures
      are also permeable to foreign chemicals. Similarly, caffeine, nicotine,
      thiopental, salicylic acid, antipyrine, barbital, and isoniazid enter the uterine
      secretion and penetrate the preimplantation blastocyst of mice, rats and rabbits.
      The pattern of distribution of compounds among ovarian follicular fluid, uterine
      luminal fluid, blastocyst and plasma varies from compound to compound and appears
      to be related to the molecular weight and degree of ionization of the compound
      and differs in pregnant and nonpregnant animals. Thus, nicotine and DDT
      accumulate in the uterine luminal fluid of pregnant but not in that of
      nonpregnant rabbits.The penetration of foreign chemicals into the oocyte, uterine
      luminal fluid, and preimplantation blastocyst may exert adverse effects on
      fertilization, implantation, and/or further development of the conceptus. The
      possible toxicological importance of this process to eutherian reproduction is
      discussed.

PMID- 17539151
TI  - Effects of ionizing radiations on mammalian oogenesis: a model for chemical
      effects.
AB  - A synopsis of the available data on the radiosensitivity of female germ cells is
      provided, the reader being referred to recent comprehensive reviews for detailed
      information. The effects of ionizing radiations are considered in terms of age;
      germ cell stage and follicular development; type, quality, and physical factors
      of the exposure; and criterion chosen to assess the effect (cell killing,
      reproductive capacity, genetic effects, etc.). A number of conclusions are drawn
      which might have a bearing on studies in which the effects of chemicals and drugs
      on mammalian species are assessed.

PMID- 17539152
TI  - Test procedures to evaluate effects of chemical exposure on fertility and
      reproduction.
AB  - Various methods have been developed to assess the effects of chemical substances
      on reproduction. In some instances, the tests have been developed to define the
      effects of treatment on specific segments of the reproductive cycle. In other
      cases, studies are conducted to determine the cumulative effects of treatment
      during one or more generations. The structure, advantages, and disadvantages of
      three types of conventional reproduction studies are reviewed. An outline of the
      procedural sequences, observations, and record evaluation required in the three
      period reproduction study, the three-generation reproduction study, and the
      multigeneration reproduction study are presented.

PMID- 17539153
TI  - Developmental aspects of the male reproductive system.
AB  - THE DEVELOPMENT OF THE MAMMALIAN REPRODUCTIVE SYSTEM INVOLVES: (1) an indifferent
      or ambisexual stage, in which both the male (Wolffian) and female (Mullerian)
      duct systems are present; (2) sexual differentiation, in which the phenotypic sex
      is expressed by the enhancement of Mullerian structures in the female and
      Wolffian structures in the male and reciprocal suppression of the opposite duct
      system; (3) cytodifferentiation, in which the epithelial, stromal and muscular
      features are regionally established; and (4) actual response to endogenous
      hormones, especially in mammals, such as the human and guinea pig, in which the
      differentiated tissues respond according to their capability. Specifically in the
      male, the onset of sexual differentiation is signaled by the elaboration of an
      androgenlike material (possibly testosterone) and a Mullerian-inhibiting factor
      from the testis. In the absence of these two influences, or one of them, the
      reproductive tract remains essentially female in configuration, a normal
      situation in the female and in abnormal males in which the urogenital sinus and
      Wolffian structures are incapable of hormonal responses due to the lack of
      specific enzymes or receptors. Male differentiation in particular involves
      enlargement of the penis and its canalization by the urethra, scrotal development
      and descent of the testis, and the formation of accessory glandular structures
      from the urogenital sinus or Wolffian ducts (bulbourethral gland, seminal
      vesicles, ampulla, prostate). Remnants of the Mullerian system may persist at the
      upper pole of the testis and are normally present (uterus masculinus) in relation
      to the prostatic part of the urethra.The emergence of the characteristic parts of
      the male reproductive system in higher mammals in relation to phylogeny and the
      detailed origin of these in individual ontogeny are described. The use of the
      guinea pig as a model animal system for the study of transplacental effects of
      hormones (diethylstilbestrol, estradiol) and teratogens is briefly discussed.

PMID- 17539154
TI  - Basic mechanisms of ovarian endocrine function.
AB  - This review outlines the current understanding of ovarian endocrine development
      and regulation with both physiological and biochemical background to provide a
      framework applicable to problems concerning environmental agents and ovarian
      endocrine function. Two approaches are used. First, the endocrine regulation of
      follicle development and corpus luteum function is considered in the classical
      sense, i.e., viewing these structures as gonadotropin-responsive units undergoing
      a programmed sequence of development and differentiation. Secondly, a relatively
      new area of ovarian physiology concerned with intra-ovarian regulation is
      explored, since this area holds potential for exploration of the direct effects
      of toxicological or environmental agents upon gonadal endocrine cells.

PMID- 17539155
TI  - Methods for perfusing the male reproductive tract: models for studying drug and
      hormone metabolism.
AB  - Methods for perfusing rat testis and accessory sex organs in situ by
      recirculating artificial medium to the hemicorpus preparation are described. The
      advantages and limitations of this system for studying the male reproductive
      tract were examined. The preparation was then used to study the uptake of
      androgens into the nuclei of caput epididymis, ventral prostate, seminal vesicle
      and testis. The accumulation of dihydrotestosterone and accessory sex organ
      nuclei was saturable and inhibited by perfusion of excess testosterone or
      cyproterone acetate. By contrast, testosterone was the major nuclear androgen in
      the testis of mature hypophysectomized preparations perfused with testosterone.
      In all parts of the reproductive tract, (3)H-nuclear androgens were associated
      with 3S, salt-extractable macromolecules within the properties of androgen
      receptors.The hemicorpus preparation was extensively compared with two techniques
      (selective and isolated) for perfusing the testis directly. Of these two
      procedures, the isolated method was superior when only the testes were studied.
      However, the hemicorpus preparation offers the advantage of studying testes along
      with the remainder of the male reproductive tract. A variety of observations
      suggest that these perfusion procedures will be useful for the study of drug as
      well as hormone metabolism and mechanism of action.

PMID- 17539156
TI  - Drugs and the blood-testis barrier.
AB  - The functional and morphological evidence for the blood-testis barrier is
      discussed, together with evidence for the various processes (simple diffusion and
      facilitated diffusion) by which various substances enter the seminiferous tubule.
      Data are presented to show that methylmethane-sulfonate (MMS) and
      dimethylnitrosamine (DMNA) both enter the seminiferous tubules rapidly, although
      from the published rates of methylation of testicular DNA, by these two
      compounds, it might be expected that the entry of DMNA would be slower than that
      of MMS. It appears, however, that DMNA in blood is gradually converted to some
      nonpermeant compound. The possibility, as yet unsubstantiated, is discussed that
      a nontoxic permeant precursor may be converted into a nonpermeant toxic substance
      inside the tubules, thereby effectively concentrating the toxic compound inside
      the tubules.

PMID- 17539157
TI  - In vitro fertilization: a potential means for toxicity testing.
AB  - Uses and potential uses of in vitro fertilization are: (1) a research tool for
      investigating biochemistry of fertilization, (2) an assay for fertilizing
      ability, (3) a potentially useful clinical approach for certain cases of
      infertility, and (4) a potentially useful means for improving animal breeding. In
      vitro fertilization methodology is sufficiently advanced for gametes of several
      mammalian species, especially mouse, rabbit, and rat, for use in evaluating
      effects imposed by toxic agents of environmental or genetic origin. Alteration of
      the normal events of fertilization and/or embryonic development following
      transfer of in vitro fertilized embryos into surrogate dams can serve as end
      point(s) in applying this means for toxicity testing. In vitro fertilization of
      mouse and rat ova has been explored as an alternative to in vivo fertilization in
      male contraceptive development studies. Original observations on toxicity of
      abnormal O(2) concentrations for rabbit fertilization in vitro are reported here.
      Ova were fertilized under 0, 20, 48, and 95% O(2), but toxicity from the extreme
      conditions, 0 and 95% was apparent from comparison of proportions of fertilized
      ova reaching the 4-cell stage during the 24-hr incubation. Toxicity was further
      evidenced by inability of embryos fertilized under 0 and 95% O(2) tensions, in
      contrast to those fertilized under 20% O(2), to sustain normal gestation
      following their transfer into recipient does. Recent success in the fertilization
      of cow ova in vitro in this laboratory provides encouragement to develop a useful
      means for testing normalcy of gametes in this species. Such studies might lead to
      useful screening procedures for avoidance of human infertility resulting from
      hazardous environmental conditions.

PMID- 17539158
TI  - Assessment of testicular toxicity in laboratory animals.
AB  - The currently available methods of assessing testicular toxicity and fertility
      are discussed. Compounds inducing testicular atrophy mainly affect the
      seminiferous epithelium, with progressive loss of spermatozoa, spermatids,
      spermatocytes, and spermatogonia. Quantitative histometric analysis of
      spermatogenesis, together with hormone assays, could be used to advantage in
      defining the underlying mechanisms of toxicity.

PMID- 17539159
TI  - Semen analysis.
AB  - In view of the well known sensitivity of the seminiferous epithelium to various
      stress factors and to chemicals one would expect that semen analyses would be
      part of many screening programs to detect dangerous chemicals and environmental
      hazards. This is not the case, and our knowledge about the production and
      functional properties of human spermatozoa is mainly based on analyses of
      specimens from men with barren marriages. A more common use of semen analyses
      should enable us to better define the normal limits for many of the potentially
      relevant variables. Due consideration must, however, also be given the time for
      spermatogenesis and for transit through the epididymis as well as the influence
      of seminal plasma factors on many functional properties of the spermatozoa. From
      the scanty information available one can already now presume that careful
      analyses of motility and morphology of the spermatozoa under standardized
      conditions will be of help in the early detection of environmental hazards. A
      more common use of methods for the assessment of such functional properties of
      the spermatozoa as structural stability, membrane permeability, metabolism, and
      resistance to physical stress will give additional information about the effects
      of chemicals and other factors. To exploit these potential methods for the early
      detection of environmental hazards there is, however, also a need of a changed
      attitude towards semen analysis from the medical profession as well as from the
      public.

PMID- 17539161
TI  - International Commission for Protection against Environmental Mutagens and
      Carcinogens (ICPEMC).

PMID- 17539162
TI  - Discussion: session 4. New approaches to detecting low-dose effects.

PMID- 17539160
TI  - Chemical-biological reactions common to teratogenesis and mutagenesis.
AB  - Cytotoxic chemicals have in common the ability to act specifically on cells in
      cycle. Bacteria are more sensitive in the exponential growth phase than when
      growing slowly in media. Similar observations have been made on a variety of
      systems ranging from bacteria, yeast, higher plants and invertebrates to
      vertebrates including primates. The embryo and fetus are highly susceptible to
      cytotoxic agents because they have continuous groups of cells in the growth
      phase. Acutely toxic doses may cause cellular death and result in developmental
      defects or fetal death. Cytotoxic agents can be grouped as alkylating agents,
      electrophilic reactants, antimetabolites, intercalating agents, amino acid
      antagonists, spindle poisons, and an additional group of chemicals which
      covalently bind to DNA. These cytotoxic groups of chemicals may also be mutagenic
      by interacting with DNA to produce changes in sequences of nucleotides resulting
      in heritable defects either in a somatic cell line or in a germinal cell line.
      The mechanisms of chemical-induced teratogenicity and mutagenicity are similar.
      This commonality is further discussed in the text.

PMID- 17539164
TI  - Discussion: session 1. Detection of health effects of exposure to low doses of
      agents-scientific constraints.

PMID- 17539163
TI  - Discussion: session 5. Epidemiologic investigation of special groups.

PMID- 17539165
TI  - Discussion: session 2. Detection of health effects of exposure to low doses of
      agents-epidemiologic problems.

PMID- 17539166
TI  - Discussion: session 3. Policy issues in applying epidemiologic evidence.

PMID- 17539167
TI  - Cytembena: Condensation of the Carcinogenesis Bioassay Technical Report.

PMID- 17539168
TI  - Di(2-ethylhexyl) adipate: Condensation of the Carcinogenesis Bioassay Technical
      Report.

PMID- 17539169
TI  - FD&C Yellow No. 6. Condensation of the Carcinogenesis Bioassay Technical Report.

PMID- 17539170
TI  - Discussion: Session IV.

PMID- 17539171
TI  - Discussion: session v.

PMID- 17539172
TI  - Discussion: session I.

PMID- 17539174
TI  - Discussion: Session II.

PMID- 17539175
TI  - Discussion: Session III.

PMID- 17539176
TI  - Biological effects of fibers: Stanton's hypothesis revisited.

PMID- 17539177
TI  - Discussion summary: environmental health-an overview.

PMID- 17539178
TI  - Discussion summary: potential hazards related to indoor pollution.

PMID- 17539179
TI  - Discussion summary: potential hazards related to other nonoccupational exposures.

PMID- 17539180
TI  - Discussion summary: alternatives for continued progress.

PMID- 17539181
TI  - Summary of discussion session: EPA workshop on the SENCAR mouse in toxicological
      testing.

PMID- 17539182
TI  - The toxicity of methyl isocyanate: Where do we stand?

PMID- 17539183
TI  - Cage allocation designs for rodent carcinogenicity experiments.
AB  - Cage allocation designs for rodent carcinogenicity experiments are discussed and
      presented with the goal of avoiding dosage group biases related to cage location.
      Considerations in selecting a cage design are first discussed in general terms.
      Specific designs are presented for use in experiments involving three, four, and
      five dose groups and with one, four, and five rodents per cage. Priorities for
      balancing treatment groups include horizontal position on shelf and shelf of
      rack, nearest neighbor balance, and male-female balance. It is proposed that
      these balance criteria be considered together with practical issues, such as the
      ability to accurately conform to a design and to determine a sensible and
      efficient design for each experiment.

PMID- 17539184
TI  - Mutual mentoring in laparoscopic urology - a natural progression from
      laparoscopic fellowship.
AB  - INTRODUCTION: The objective of this study is to report a novel system of 'mutual
      mentoring' that overcomes the limited availability of laparoscopic mentors and
      allows progression from laboratory and fellowship experience into independent
      clinical practice. PATIENTS AND METHODS: A total of 88 laparoscopic cases were
      performed during the fellowship. In the first 2 years as consultants, we (AJ and
      MS) performed 151 cases with mutual mentoring (simple nephrectomy [n = 28],
      radical nephrectomy [n = 35], nephro-ureterectomy [n = 19], pyeloplasty [n = 31],
      pelvic LND [n = 21], others [n = 17]). RESULTS: Mutual mentoring has resulted in
      the successful introduction of laparoscopic services to two hospitals, allowing
      an exposure to an average of two cases a week. Complication rates are acceptable
      and objective measures such as conversion rates, operative time and blood loss
      appear to be improving. CONCLUSIONS: Mutual mentoring allows for a greater
      through-put of cases, a high level of assistance, advice with intra-operative
      decisions and the potential to 'share' cases, reducing fatigue and increasing
      experience. It provides significant moral support in the difficult early days of
      starting the service. Its disadvantages are that it is time consuming and is
      geographically restrictive. Mutual mentoring has allowed us to introduce a
      laparoscopic service at our respective hospitals with high case-load acceptable
      complication rates.

PMID- 17539185
TI  - Excision of metatarsal bone and metatarsophalangeal  (MTP) joint in neuropathic 
      diabetic foot ulcer.

PMID- 17539186
TI  - A new technique for reduction of paediatric  femoral fractures using elastic
      stable  intramedullary nails.

PMID- 17539187
TI  - A low-cost technique for measuring the intraabdominal  pressure in non
      industrialised countries.

PMID- 17539188
TI  - Using video-assisted thorascoscopy (VATS)  to aid the anterior mediastinotomy
      approach  to mediastinal masses.

PMID- 17539189
TI  - Accuracy of subacromial injections.

PMID- 17539190
TI  - What type of orthosis is most effective in treating chronic plantar fasciitis?

PMID- 17539191
TI  - Knee cartilage defects and factors affecting change.

PMID- 17539192
TI  - Highlights from: 5-Fluorouracil Drug Management Pharmacokinetics and
      Pharmacogenomics Workshop; Orlando, Florida; January 2007.

PMID- 17539193
TI  - Costs of community-acquired pediatric rotavirus gastroenteritis in 7 European
      countries: the REVEAL Study.
AB  - BACKGROUND: Morbidity and resource use due to rotavirus gastroenteritis (RVGE)
      are substantial in Europe, although comprehensive data on the economic impact of
      the disease are lacking. METHODS: A cost study was conducted to assess health
      care resource use data collected during a prospective epidemiologic study of
      acute gastroenteritis in children <5 years of age in selected areas of Belgium,
      France, Germany, Italy, Spain, Sweden, and the United Kingdom. We calculated the
      average cost (direct and indirect) per episode of confirmed RVGE in primary care,
      emergency department, and hospital settings. RESULTS: The total societal cost
      (including direct medical, direct nonmedical, and indirect costs) per episode of
      RVGE ranged from 166 euros to 473 euros in the primary care setting, from 334
      euros to 770 euros in the emergency department setting, and from 1525 euros to
      2101 euros in the hospital setting. The majority of hospital-related costs were
      reimbursed by national health care payers, but the percentage of reimbursed costs
      declined progressively in the emergency department and primary care settings. The
      mean number of workdays lost by parents and other relatives varied between study
      areas and settings, ranging from 2.3 to 7.5 days, and this represented the major
      cost not reimbursed by national health care payers. CONCLUSIONS: RVGE incurs
      considerable resource utilization in all health care settings and substantial
      costs for national health care payers, families of patients, and employers.
      Routine rotavirus vaccination in infants could significantly reduce the health
      and economic burden of pediatric RVGE.

PMID- 17539194
TI  - Heart Rhythm 2007. Abstracts of the 28th Annual Scientific Sessions of the Heart
      Rhythm Society, May 9-12, 2007, Denver, Colorado, USA.

PMID- 17539195
TI  - [Role of positron emission tomography in geriatric medicine].

PMID- 17539196
TI  - [Molecular mechanisms of neurodegeneration in polyglutamine diseases].

PMID- 17539197
TI  - Sleep 2007. Abstracts of the 21st Annual Meeting of the Associated Professional
      Sleep Societies, LLC, June 9-14, 2007, Minneapolis, Minnesota, USA.

PMID- 17539198
TI  - Galileo's tidal theory.
AB  - The aim of Galileo's tidal theory was to show that the tides were produced
      entirely by the earth's motion and thereby to demonstrate the physical truth of
      Copernicanism. However, in the Dialogue Concerning the Two Chief World Systems
      Galileo did not explain some of the most significant aspects of the theory
      completely. As a consequence, the way the theory works has long been disputed.
      Though there exist a number of interpretations in the literature, the most widely
      accepted are based on ideas that are not explicitly articulated by Galileo in the
      Dialogue. This essay attempts to understand the way the theory functions in terms
      of Galilean physics. It is an interpretation of the theory based solely on
      Galileo's arguments--and one that reveals it to have had some unrecognized
      consequences. This interpretation indicates that Galileo's theory would not have
      worked in the manner he described in the Dialogue.

PMID- 17539199
TI  - Becoming an expert practitioner: court experimentalism and the medical skills of
      Anna of Saxony (1532-1585).
AB  - This essay proposes that the well-documented interest in empirical and
      experimental practice at the early modern German courts was not limited to male
      practitioners. Just as princes evinced an interest in practical alchemy,
      mathematics, and astronomy, a large number of gentlewomen became expert medical
      practitioners. Using a case study of one noblewoman, Electress Anna of Saxony, I
      would like to expand the notion of "prince-practitioning" to a more general and
      inclusive "court experimentalism." Like the prince-practitioners, Anna engaged in
      a laborious attempt to learn the hands-on techniques involved in becoming an
      expert; she collaborated with both noblewomen and noblemen in her efforts; and
      she semantically linked her medicine to the alchemical skills (Kunste) practiced
      by her husband, Elector August. Although court experimentalism cannot be equated
      with experimentation in the modern sense, medicine is one area in which women
      actively shared in the early modern fascination with empirical knowledge.

PMID- 17539200
TI  - Neuroses of the stomach: eating, gender, and psychopathology in French medicine,
      1800-1870.
AB  - In the period 1800-1870, French physicians approached psychic illness (Philippe
      Pinel's "neurosis") within competing "cerebralist" and "visceralist" frameworks.
      Cerebralism, which dominated the specialty of mental medicine, sought the origins
      of psychic illness in lesions of the brain and central nervous system.
      "Visceralism," upheld by generalists, clung to the view of the ancients that
      psychic disorder was seated in the abdominal viscera. The distinction enjoyed
      credibility thanks to widespread acceptance of Xavier Bichat's "two lives"
      doctrine, which demarcated functions of the central and the "vegetative" nervous
      systems. Once the "two lives" conception was undercut after midcentury,
      cerebralists sought to draw disturbances of appetite, digestion, and eating
      within the domain of the central nervous system. This essay suggests that
      historical study of "hysterical anorexia" and related disease entities that
      displaced "neuroses of the stomach" has overemphasized sociocultural determinants
      to the neglect of the internal dynamics of biomedical science.

PMID- 17539201
TI  - Radiologic case study. Gout.
AB  - Characteristic imaging finding of chronic gout include eccentric soft-tissue
      abnormalities, sometimes calcified, that have overly well defined erosions with
      sclerotic margins and overhanging edges, and preservation of bone density. While
      the triad of acute monoarticular arthritis, hyperuricemia, and prompt response to
      drug therapy is highly suggestive of acute gouty arthritis, the radiographic
      findings during an acute attack are nonspecific.

PMID- 17539202
TI  - Improving orthopedic outcomes: focus on rehabilitation.

PMID- 17539203
TI  - Retrograde nailing of supracondylar periprosthetic femur fractures: a surgeon's
      guide to femoral component sizing.

PMID- 17539204
TI  - The slippage-proof knot: a new, nonstacking, arthroscopic, sliding locking knot
      with a lag bight.

PMID- 17539205
TI  - Range of motion after total hip resurfacing.

PMID- 17539206
TI  - Review of alcohol withdrawal in the hospitalized patient: diagnosis and
      assessment.

PMID- 17539207
TI  - Management of in-season anterior shoulder dislocation in the amateur athlete.

PMID- 17539208
TI  - ACL injuries in the skeletally immature patient.
AB  - Anterior cruciate ligament injuries in the pediatric and adolescent population
      are becoming more common with the trends of increased participation in
      competitive athletics in younger children. The natural history of this injury is
      similar to that of the adult and results in frequent reinjury, instability, and
      debilitation. Delayed reconstruction has proven to be a clinically effective
      treatment method but requires a prolonged restriction of competitive athletics.
      Reconstruction in the acute and subacute period has been shown by many authors to
      be a successful, reproducible treatment regimen. Nonetheless, the unique pitfalls
      of ACL reconstruction in a skeletally immature patient must not be overlooked. A
      thorough preoperative evaluation for leg-length discrepancy or subtle angular
      deformity is essential to identify the presence of an entity that might otherwise
      be attributed to surgical complication. For the patient nearing skeletal maturity
      with little growth remaining, we recommend the standard tunnel positioning and
      the use of soft-tissue graft. For younger patients who have significant growth
      remaining, alternative physeal "safe" procedures should be considered. No
      prospective, randomized studies compare the clinical success of graft type, graft
      placement, or graft fixation in this age group. Further follow-up of existing
      study groups and prospective research is warranted to fine-tune the result-based
      decision making for treatment of this injury.

PMID- 17539209
TI  - Total knee arthroplasty in patients with pre-existing fracture deformity.
AB  - Pre-existing femoral or tibial extra-articular fracture deformity may adversely
      affect the results of total knee arthroplasty (TKA). This deformity can be
      addressed with asymmetrical intra-articular resection or with correctional
      osteotomy performed prior to or at the time of primary TKA. Careful preoperative
      planning obviates many potential problems that can occur at the time of surgery
      with correction of many complex deformities.

PMID- 17539210
TI  - Outcomes assessment of pediatric both-bone forearm fractures treated operatively.
AB  - This study assessed the outcome of pediatric both-bone forearm fractures treated
      with operative intervention. A retrospective review was conducted of 31 patients
      treated over a 40-month period. Fifteen patients were treated with flexible
      intramedullary nailing and 16 treated with open reduction and internal fixation.
      Average patient age was 11 years (range: 3.8-17.9 years). Operative indications
      included 2 open fractures and 29 fractures with unacceptable reductions. The
      intramedullary nailing group had 14 excellent results and 1 good result. The open
      reduction internal fixation group had 15 excellent results and 1 good result.
      Overall, 29 (93.5%) of 31 patients had excellent results. Two minor complications
      occurred in the intramedullary nailing group and none in the open reduction
      internal fixation group. Although operative intervention in pediatric both-bone
      forearm fractures is rarely indicated, when necessary, good results can be
      expected.

PMID- 17539211
TI  - Proximal femoral replacement for metastatic bone disease.
AB  - Between 1994 and 2000, 13 patients (8 women and 5 men; 14 hips) underwent
      proximal femoral replacement secondary to metastatic disease. Average patient age
      was 62 years (range: 46-77 years). The most common diagnosis was renal cell
      carcinoma. Seven pathologic fractures were noted. Patients ambulated with full
      weight bearing postoperatively and wore an abduction brace for 3-4 months. Ten
      patients died of their diseases at 0.5-3.5 years postoperatively. No
      dislocations, infections, or reoperations occurred. Proximal femoral replacement
      provides excellent pain relief and good restoration of function when more simple
      reconstructive options are not feasible.

PMID- 17539212
TI  - Transforaminal lumbar interbody fusion: a retrospective study of long-term pain
      relief and fusion outcomes.
AB  - No long-term studies exist on the effectiveness of transforaminal lumbar
      interbody fusion. This study sought to determine postoperative pain, disability,
      and fusion status of transforaminal lumbar interbody fusion patients after > or =
      4 years to establish long-term outcomes. A retrospective analysis of 42 patients
      with minimum 4-year follow-up was conducted. Patients completed visual analog
      pain scale (VAS) and Oswestry functional capacity evaluation pre- and
      postoperatively. Statistically significant improvement was noted in VAS and
      Oswestry functional capacity evaluation scores. Transforaminal lumbar interbody
      fusion is effective in alleviating intractable back pain over an extended time
      period. Solid radiographic fusion is unnecessary for clinically successful
      outcomes.

PMID- 17539213
TI  - Remodeling of tibial fractures in children younger than 12 years.
AB  - Forty-eight children with an average age of 7.2 years (range: 3-12 years) were
      examined clinically and radiographically at an average 4-year follow-up (range: 2
      10 years), between 1989 and 2000 to analyze correction of deformities following
      tibial shaft fractures. An inconsistent alteration in the length of the fractured
      tibia was observed. Anterior angular deformity realigned maximally (52.7%)
      followed by varus (40.9%) and valgus (23.9%) deformities. Posterior deformity
      corrected the least (18.5%). In the sagittal plane, acceptable critical anterior
      and posterior angular deformities that corrected completely were 12 degrees and 6
      degrees respectively. In the coronal plane, acceptable critical angular
      deformities were 10 degrees varus and 8 degrees valgus.

PMID- 17539214
TI  - Incision stretching in primary TKA: what is the real length of our approach?
AB  - This article examines the extent of anterior knee soft-tissue stretching that
      occurs in patients undergoing primary total knee arthroplasty for 331 consecutive
      patients. At the time of surgery, an anterior knee incision was drawn on the
      knee. Measurements were taken of the length of the incision with the knee in
      maximum extension and 90 degrees degrees of flexion. Incision length was 5.7 cm
      longer in flexion than extension. The surgical incision site stretched an average
      of 23.6% in flexion compared to the resting extension length.

PMID- 17539215
TI  - Pseudoaneurysm from a traumatic osteochondroma leading to rapid neurological
      compromise.

PMID- 17539216
TI  - Bilateral THA in a patient with Waldenstrom's macroglobulinemia.

PMID- 17539217
TI  - Recurrence of chronic osteomyelitis in a regenerated fibula after 65 years.

PMID- 17539218
TI  - I teach special needs dentistry...

PMID- 17539219
TI  - Reduction in caries rate among patients with xerostomia using a power toothbrush.
AB  - The purpose of this study was to evaluate whether the use of a Sonicare
      toothbrush could be beneficial in reducing coronal and/or root caries among
      patients with medication-induced xerostomia. Eighty subjects with drug-induced
      xerostomia using either a Sonicare toothbrush (SC) or a manual toothbrush (MTB)
      were included in the study. Control subjects using a MTB were frequency-matched
      to 40 subjects using a SC, based on age, gender, number of teeth at baseline, and
      salivary flow rates. Subjects were individually matched according to the type of
      xerostomic medication they were taking. Caries were assessed at baseline, and
      subjects were instructed to have carious teeth restored. Summary statistics were
      assessed and computed by treatment group for incipient and frank coronal and root
      caries after one year. Statistical comparisons of the number of frank and
      incipient coronal and root caries between treatment groups were conducted using
      paired t-tests. After one year of use, the numbers of incipient and frank root
      caries were significantly lower among subjects using SC compared to subjects
      using MTB. Subjects using SC also exhibited somewhat lower incipient and frank
      coronal caries than subjects using MTB, although their differences were not
      statistically significant. The authors concluded that the Sonicare toothbrush may
      be beneficial in reducing root caries among older adults with medication-induced
      xerostomia.

PMID- 17539221
TI  - Severe gingival recession and early loss of teeth in a child with chronic graft
      versus host disease: a case report.
AB  - Graft versus host disease (GVHD) occurs after a hematopoietic stem cell
      transplantation (HSCT) when the donor's immune system rejects the recipient's
      body, leading to significant morbidity and mortality. Increased numbers of
      chronic GVHD (c-GVHD) patients are likely to be seen by dental professionals
      because of the advances made in transplantation. The oral cavity may be the
      primary or the only site of c-GVHD and may have persistent lesions after
      resolution has occurred in other areas. Approximately 80% of patients with
      extensive c-GVHD present some type of oral involvement, including xerostomia,
      oral pain and lesions. Dental and oral care can be challenging for these
      patients. This paper discusses the manifestations and treatment of oral c-GVHD
      and presents the case history of a 15-month-old girl who developed severe oral
      GVHD with an unusual periodontal presentation and early loss of primary teeth.

PMID- 17539220
TI  - Prevalence of oral diseases in Shwachman-Diamond syndrome.
AB  - The aim of this study was to determine the prevalence and severity of oral
      diseases in patients with ShwachmanDiamond syndrome (SDS). Thirty-five persons
      with SDS were compared to 20 healthy controls. A cross-sectional survey was
      carried out using self-reporting questionnaires and dental radiographs collected
      from the subjects and their dentists. Overall, oral diseases were more prevalent
      among subjects with SDS when compared to controls (p < 0.001). Persons with SDS
      also had more caries in both primary (p < 0.03) and permanent dentitions (p <
      0.01), and also had delayed dental development (p < 0.04). Oral soft tissue
      pathoses, such as recurrent oral ulcerations (p < 0.00) and gingival bleeding
      upon brushing (p < 0.00), were significantly more prevalent in subjects with SDS.
      Pain on eating was also more frequent amongst persons with SDS (p < 0.008) and
      was often associated with oral ulcerations (p < 0.002). In conclusion, based on
      self-completed subject and dentist questionnaires, diseases of oral hard and soft
      tissues were more prevalent and severe in persons with SDS when compared with
      healthy controls.

PMID- 17539222
TI  - The influence of valproic acid on salivary pH in children with cerebral palsy.
AB  - The purpose of this open-label, crossover study was to measure salivary pH after
      the oral administration of distilled water, a 10% sucrose solution, and valproic
      acid to a population of 10 children with cerebral palsy. Salivary pH was measured
      just prior to giving the solutions and then every five minutes for 60 minutes.
      The critical pH was defined at 5.5, below which dental demineralization occurs.
      In this population, valproic acid decreased salivary pH to below the critical pH
      for an extended period of time (mean = 4.32 at 20 minutes) when compared to mean
      salivary pH after administration of distilled water (7.11 at 20 minutes) and a
      10% sucrose solution (5.96 at 20 minutes). Recovery from this low pH to above the
      critical level did not occur until after 50 minutes and furthermore did not
      recover to baseline, neutral levels, for the duration of this study (60 minutes).
      Our results suggest that children with cerebral palsy, a population with a
      tendency toward reduced salivary function, have a compromised ability to buffer
      the oral administration of an exogenous acid. This can result in an increased
      susceptibility to demineralization and caries of the teeth.

PMID- 17539223
TI  - The prevalence and antibiotic sensitivity of oral Viridans streptococci in
      healthy children and children with disabilities in Kuwait.
AB  - The purpose of this study was to compare the antibiotic susceptibility profiles
      of Viridans streptococci (VS) isolated from the oral cavity of healthy children
      and children with disabilities in Kuwait. Plaque samples were collected from the
      tooth and tongue surfaces of 102 healthy children and 102 children who were
      intellectually disabled and institutionalized. The resistance to seven
      antibiotics (amoxicillin, cephalothin, clindamycin, erythromycin, penicillin G,
      tetracycline, and vancomycin) was tested. A total of 330 (44.5%) VS were isolated
      from the children who were healthy and 411 (55.5%) from children with
      disabilities. The most common isolates were S. salivarius (27.3%) in healthy
      children; S. sanguis (22.6%) was predominant among children who were disabled. S.
      mutans was found in 12.1% of the healthy children and in 16.5% of the children
      who were disabled. The combined percentage of resistant strains (healthy and
      disabled) was found to be highest with amoxicillin (43%) and lowest with
      vancomycin (12%). S. sanguis, S. mitis and S. oralis were more resistant in
      healthy children (45%, 56%, and 55% respectively) than in children with
      disabilities (40%, 47% and 47% respectively). S. mutans was the least resistant
      species to all antibiotics in both groups of children. About 56% of all
      streptococci isolated from both groups were resistant to at least one of the
      antibiotics tested. The data showed that there was a difference in the level of
      resistance of oral VS isolated from healthy children and children with
      disabilities to some antibiotics commonly used in dentistry.

PMID- 17539224
TI  - Occurrence of bruxism in a sample of Brazilian children with cerebral palsy.
AB  - Bruxism has been reported to exist in many children with cerebral palsy; however,
      only a few studies confirm this fact. The objective of this study was to
      determine the rate of bruxism in children with cerebral palsy and to relate its
      presence to the following factors: kind of cerebral palsy, gender, age,
      dentition, degree of malocclusion, oral mucous membrane trauma, trismus, and
      number of wear facets on specific teeth. The guardians of 121 children with
      cerebral palsy between the ages of 4 and 9 years were interviewed and the
      children were clinically examined. Bruxism was detected in 69.4% of the children
      and reported by 57% of the guardians. In 4- and 5-year-old children, the rate of
      wear facets was small. Children with athetosis and spastic tetraplegia had a
      higher rate of bruxism than all others.

PMID- 17539225
TI  - Tennessee ranks comparatively high in some health measures, but...
AB  - State ranking and proportion reports from the United Health Foundation and the
      Annie E. Casey Foundation on health and social conditions are used to demonstrate
      the difficulties faced by the State of Tennessee in its effort to provide for the
      needed services for its residents. The concerns faced by the dental profession,
      in its effort to provide needed oral health services, are a component of the
      complexities to improve the modest ranking of the state in a series of health and
      social attributes.

PMID- 17539226
TI  - Metastatic adenocarcinoma of the breast presenting as pulpal/periodontal disease.

PMID- 17539227
TI  - Accessing and restoring root caries: a case report.
AB  - Adequate access to root caries can be problematic. The inability to view,
      isolate, and access the entire lesion may result in residual caries, poor
      adaptation of the restoration, and defective margins. Minor periodontal
      procedures, ranging from a mini-flap involving only one tooth, to conventional
      flap surgery can provide increased visibility and access to these troublesome
      areas. Through utilization of this technique, excellent preparations and
      restorations can be achieved. Restorative materials with a high potential for
      fluoride release as well as uptake should be highly considered in cases of root
      caries. The selection of a conventional or resin-modified glass ionomer provides
      several advantages. Most notably are the ability of these restoratives to
      chemically bond to tooth structure, and to provide significant fluoride release
      and uptake. These properties are not present in amalgam, composites, or
      compomers. Additionally, the material itself is relatively easy to use and
      provides an effective zone of caries inhibition around the margins of the
      restoration. Glass ionomers are not as sensitive to moisture as conventional
      resin composites or compomers, and, as a result, may provide a better bond to
      tooth structure and margination in areas where moisture control is troublesome.
      Finally, the polymerization shrinkage of these materials is not as great as resin
      composites, which should also improve marginal integrity. Clinical studies have
      demonstrated longevity of ten years or greater as well as success in xerostomic
      patients. Management of xerostomic patients should be directed toward finding
      satisfactory methods to relieve dryness. Some prescription medications are
      available, but should only be recommended after consultation with the primary
      care physician. Oral moisturizers are also available as are saliva substitutes.
      Caution should be used when recommending saliva substitutes due to the fact that
      some commercial products have been demonstrated to have a pH below the
      demineralization point of enamel. Products of this nature should be avoided. In
      the last few decades, the age of the patient population has increased and
      individuals have a greater tendency to maintain their natural dentition
      throughout their entire life. Gingival recession and subsequent root exposure has
      become more prevalent in the adult population. Additionally, the use of
      prescription medications that impact the flow and consistency of saliva is
      widespread. As a result of these phenomena, it has been predicted that root
      caries will become more prevalent. When preventive measures prove to be
      ineffective and restorations must be placed, access, visibility, and appropriate
      material selection are paramount. A combined minor periodontal surgery and
      restorative procedure is relatively simple, and when done properly, can provide
      excellent and affordable dentistry in these problematic areas.

PMID- 17539228
TI  - What guides professional behavior of dentists?
AB  - The purpose of this paper is to explore the question of what guides professional
      behavior in the hope that those who read it will reflect on how they conduct
      their relationships with patients, business associates, and employees. I propose
      that the ADA Principles of Ethics and Code of Professional Conduct are only a
      portion of what guides dentists' ethical behavior. The Principles and Code are
      founded on basic personal ethics and societal standards, and in the U.S. they are
      in turn the foundation for the state dental practice acts.

PMID- 17539229
TI  - Healthcare reform: an uphill fight.

PMID- 17539230
TI  - Medicine is a blame game.

PMID- 17539231
TI  - Coding cues. Advance beneficiary notices.

PMID- 17539232
TI  - Dealing with an impaired colleague.

PMID- 17539233
TI  - Watch out for EHR audit pitfalls.

PMID- 17539234
TI  - Personnel files: documentation is key.

PMID- 17539235
TI  - I hug, I kiss, and I cry.

PMID- 17539236
TI  - How to pick a password.

PMID- 17539237
TI  - Religion in the exam room: does it belong?

PMID- 17539238
TI  - IgG antibody profile to c-terminal region of Plasmodium vivax merozoite surface
      protein-1 in Thai individuals exposed to malaria.
AB  - Naturally acquired immune response to C-terminal region of Plasmodium vivax
      merozoite surface protein1 (PvMSP1) in 200 individuals with recent clinical
      episodes of malaria from malaria endemic areas along Thai-Myanmar border in the
      west and Thai-Cambodia border in the east of Thailand was evaluated by enzyme
      linked immunosorbent assay (ELISA). The anti-PvMSP1-IgG antibody was observed in
      110 individuals (55%). Among IgG responders, IgG1 coexpressed with IgG3 were the
      predominant subclasses. The levels of anti-PvMSP1 total IgG, IgG1 and IgG3
      antibody response seem to be increased with age although no detectable
      significant correlation was found (r = 0.004, p = 0.484 for total IgG; r = 0.035,
      p = 0.386 for IgG1; r = -0.600, p = 0.142 for IgG2; r = 0.077, p = 0.227 for
      IgG3; r = 0.664, p = 0.051 for IgG4). However, the mean level of specific total
      IgG was highest in the age group of >40 years. These levels of either specific
      total IgG or each IgG isotype did not vary among individuals with different
      malaria episodes. A higher level of specific total IgG, IgG1 and IgG3 antibody
      response related with the lower of parasitemia density was observed although no
      significant correlation was found. Our data indicate that individuals exposed to
      vivax malaria in Thailand developed antibodies to the potential candidate vaccine
      antigen, PvMSP1 (C-terminal).

PMID- 17539239
TI  - Autochthonous visceral leishmaniasis: a report of a second case in Thailand.
AB  - Visceral leishmaniasis (VL) is a rare disease in Thailand. Only one previous case
      has been reported in which transmission was likely autochthonous. We conducted an
      investigation of a case of VL, which included serological and symptom surveys of
      people who lived near the case in Nan Province and Bangkok, serological surveys
      of domestic animals in his home village and sand fly surveys in his home village
      and in Bangkok. No humans interviewed met our case definition for possible VL.
      One hundred thirty-one villagers were seronegative for Leishmania antibodies. We
      found three cows and one cat that had positive direct agglutination tests for
      Leishmania spp, but we were unable to confirm current infection by PCR. Sand fly
      surveys showed that most of the flies were of the Sergentomyia genus, which has
      not previously been reported as a competent vector in Thailand. Nonetheless, we
      conclude, based on the patient's lack of travel outside Thailand and the presence
      of seropositive domestic animals in his home village, that he was most likely
      infected by the bite of a sand fly in Thailand. We believe this is the second
      case of autochthonously transmitted VL in Thailand.

PMID- 17539240
TI  - Intestinal protozoal infestation profile in persistent diarrhea in children below
      age 5 years in western Nepal.
AB  - Unlike acute diarrhea, the role of pathogens in persistent diarrhea in children
      in Nepal is unclear. Protozoal parasites are suspected to be a major cause. The
      study was carried out to find the association between protozoal agents and
      persistent diarrhea in children below age 5 years from western Nepal. Stool
      samples were collected from 253 children with persistent diarrhea, from 155
      children with acute diarrhea (disease controls) and from 100 healthy children
      from the community (normal controls). Of 253 children with persistent diarrhea,
      90 (35.5%) had protozoal infections, 63 (24.9%) helminthic infections, 32 (12.6%)
      had bacterial infections and 16 had mixed infections. Giardia lamblia was the
      most prevalent (67.7%), followed by Entamaeba histolytica (27.7%). HIV infection
      and severe malnutrition were associated with Cyclospora cayetanensis and
      Cryptosporidium spp causing persistent diarrhea. We conclude that stool
      microscopy should be routinely performed in children with persistent diarrhea
      since protozoal infections can be cured with effective treatment and control can
      be achieved by proper health education.

PMID- 17539241
TI  - Relationship between Enterobius vermicularis and the incidence of acute
      appendicitis.
AB  - The objective of this study was to evaluate the relationship between Enterobius
      vermicularis and the occurrence of acute appendicitis. Over a ten year period of
      time, all appendix specimens received by the department of pathology were
      reviewed for pathologic changes and the existence of E. vermicularis. Logistic
      regression was carried out to determine the odds ratio (OR) of the relationship
      between E. vermicularis and acute appendicitis. A total of 5048 specimens were
      reviewed. E. vermicularis was found in 144 (2.9%) cases. After separating by sex
      and adjusting for age logistic regression analysis showed the OR of E.
      vermicularis appendiceal infestation was 1.275 (95% CI = 0.42-3.9) for males and
      1.678 (95% CI = 0.61-4.65) for females. Age was an independent risk factor for
      acute appendicitis in males (OR = 1.01, 95% CI = 1.003-1.017) and females (OR =
      1.012, 95% CI = 1.005-1.02).

PMID- 17539242
TI  - Eosinophilic meningitis associated with angiostrongyliasis: clinical features,
      laboratory investigations and specific diagnostic IgG and IgG subclass antibodies
      in cerebrospinal fluid.
AB  - Eosinophilic meningitis (EOM) associated angiostrongyliasis mostly induced by the
      nematode Angiostrongylus cantonensis, is a common disease with worldwide
      prevalence. Heavy infections can lead to chronic disabling disease and even
      death. This study was conducted to shed light on the overall specific IgG
      antibody response as well as the specific IgG antibody subclass responses in
      cerebrospinal fluid (CSF) of patients with EOM. Fifteen patients with EOM
      associated with angiostrongyliasis were included in the study. Sera were screened
      by immunoblotting for the presence of IgG antibody to the 29 kDaA. cantonensis
      antigenic polypeptide. CSF was examined by ELISA for the presence of specific IgG
      and IgG subclass antibodies. Patients presented with headache (100%), neck
      stiffness (20%), fever (40%), nausea (87%), vomiting (73%), paresthesia (7%), and
      muscle weakness (7%). Seven of 15 (47%) patients showed peripheral blood
      eosinophilia and all patients presented with eosinophils in CSF. A sensitivity of
      80 % was obtained by combining the diagnostic values of immunoblotting in sera
      and IgG and IgG subclasses-based ELISA in CSF. The combination of a history of
      eating raw or semi-cooked infected foods, clinical features, complete blood
      count, differential cell counts, CSF profiles, and serum and CSF antibodies to A.
      cantonensis can be used to increase the sensitivity for the diagnosis of human
      angiostrongyliasis.

PMID- 17539243
TI  - Urinary tract pathology in Schistosoma haematobium infected rural Nigerians.
AB  - Parasitological investigation assessing the ova of Schistosoma haematobium in the
      urine of 138 volunteers in Ihieve-Ogben, Edo State, Nigeria revealed 43 positive
      results (31.2%). Children had a higher prevalence of urinary schistosomiasis 30
      (41.1%) than their adult counterparts 13 (20.0%) and this difference was
      statistically significant (t = 8.89, p > 0.01). More volunteers had light
      intensity of infection 27 (19.6%) than heavy infection 16 (11.6%) and this
      difference was statistically significant (chi2 = 22.90, p>0.05). Ultrasonographic
      investigations carried out on these 43 S. haematobium infected volunteers
      revealed ten pathological conditions, including abnormal wall thickness 24
      (55.8%), abnormal shape 30 (69.8%), irregular bladder wall 12 (27.9%), masses 10
      (23.3%), pseudopolyps 2 (4.7%), echogenic particles 30 (69.8%), residual volume
      12 (27.9%), calcifications 24 (55.8%), hydroureter 10 (23.3%) and hydronephrosis
      8 (18.6%) when compared to control subjects which lacked bladder and kidney
      abnormalities. These pathological conditions were slightly more common in the
      volunteers with heavy infection than those with light infection, but this
      difference was not statistically significant (t = -2.19, p < 0.02). More
      pathological conditions were found in children than in adults; this finding was
      statistically significant (t = 3.23, p > 0.03). Hydronephrosis and hydroureter
      were not found in the volunteers with light intensity of infection.

PMID- 17539244
TI  - Comparison between Musca domestica and Chrysomya megacephala as carriers of
      bacteria in northern Thailand.
AB  - A comparison between the common house fly, Musca domestica, and the Oriental
      latrine fly, Chrysomya megacephala, was assessed for their potential as carriers
      of bacteria in urban areas of Chiang Mai Province, northern Thailand. C.
      megacephala was significantly more likely to carry bacterial species than M.
      domestica; however, no significant difference was found between the number of
      positive male and female flies within the same species. A total of 42 bacterial
      species were isolated. The most common bacterium isolated from M. domestica was
      coagulase-negative staphylococci (n=57) followed by Escherichia coli (n=10) and
      Viridans streptococci (n=10), while that of C. megacephala was non-fermentative
      gram-negative bacilli (n=59) followed by coagulase-negative staphylococci (n=54).

PMID- 17539245
TI  - Hepatitis B virus sero-markers, hepatitis C virus antibody and risk behaviors
      among middle age and older Thai males.
AB  - A cross-sectional study of 1069 Thai males over 40 years of age was carried out
      to assess risk behaviors towards hepatitis B and C. All studied participants who
      voluntarily participated and signed informed consents were interviewed. One
      hundred eighty-seven volunteers participated in blood screening for hepatitis B
      virus (HBV) sero-markers and anti-hepatitis C virus (anti-HCV). The results
      reveal of 1069 subjects, 21.3% had tattoos, 18.4% had a history of regular
      alcohol consumption (drinking alcohol > or =5 days/week), and 16.4% had a history
      of extramarital sex without using condoms during the previous year. Results from
      blood screening showed 93.1% were positive for HBV sero-markers, 4.3% had a
      positive HBsAg, 58.8% had a positive anti-HBs, and 0.5% had a positive anti-HCV
      antibody. Nine subjects were positive for HBsAg or anti-HCV, most (7/9) had at
      least one risk behavior.

PMID- 17539246
TI  - Real-time PCR analysis of dog cerebrospinal fluid and saliva samples for ante
      mortem diagnosis of rabies.
AB  - The use of a 10-day observation to determine whether a dog is rabid is standard
      practice. This study was conducted in order to look for evidence of rabies vius
      in saliva and cerebrospinal fluid (CSF) of suspected live rabid dogs at the time
      of quarantine by using a SYBR Green real-time RT-PCR based assay for the
      detection of rabies virus RNA. Saliva and CSF of dogs were collected once on the
      day of admission for the 10-day quarantine. All test dogs were or became ill and
      died of rabies within the observation period. Thirteen of 15 dogs (87%) had
      saliva samples that were positive for rabies RNA. Two dogs with furious rabies
      had negative saliva samples. Positive CSF samples were found in 4 of 15 dogs
      (27%) whose saliva samples were positive. The time from sample collection to
      result was less than 5 hours. Because virus may be absent or present at very low
      level in both clinical fluids, samples taken for ante-mortem diagnosis cannot
      definitively rule out rabies.

PMID- 17539247
TI  - Human immunodeficiency virus (HIV) related cryptococcal meningitis in rural
      central Thailand--treatment difficulties and prevention strategies.
AB  - In 2000, cryptococcal meningitis was a common HIV related opportunistic infection
      in central Thailand requiring inpatient management but few patients suffering
      from it could afford a full course of treatment once infection had occurred.
      Since then, the production of generic fluconazole and highly active
      antiretroviral therapy (HAART) in Thailand (and national guidelines regarding
      their use) is reducing the incidence of this condition and such a strategy of
      prevention appears much more effective than treating established disease. There
      remains a continuing need for health education in the region and the removal of
      stigma associated with this disease so that earlier detection of HIV infection
      and the implementation of these national guidelines can have their greatest
      impact.

PMID- 17539248
TI  - Opportunistic infections and HIV clinical disease stage among patients presenting
      for care in Phnom Penh, Cambodia.
AB  - This prospective, cross-sectional study sought to assess the spectrum of HIV
      associated complications and disease stage among individuals presenting for first
      time care in Phnom Penh, Cambodia between November 2001 and September 2002. One
      hundred patients participated in this study. All study participants presented
      with advanced stages of HIV disease. Seventy-four percent of the subjects had CD4
      cell counts <50 cells/mm3. Tuberculosis was the most common AIDS-defining illness
      among participants, with a prevalence of 43%. A spectrum of other opportunistic
      infections, including cryptosporidiosis (13%), severe bacterial infections (12%),
      cryptococcosis (12%), and Pneumocystis jiroveci pneumonia (10%), was identified.
      These findings underscore the need for widespread HIV treatment and prevention in
      this setting. Increased screening for HIV and routine health maintenance for
      those infected are urgently needed in order to facilitate management of both
      opportunistic infections and the secondary prevention of HIV infection.

PMID- 17539249
TI  - Lipid profiles of Thai adult HIV-infected patients receiving protease inhibitors.
AB  - Dyslipidemia is a common metabolic complication among HIV-infected patients who
      receive protease inhibitor (PI)-based antiretroviral therapy (ART). In order to
      assess the prevalence of lipid abnormalities and related factors, a cross
      sectional analytic study of the lipid profiles of 170 Thai adult HIV-infected
      patients receiving PI-containing HAART who attended the HIV-clinic, King
      Chulalongkorn Memorial Hospital, Bangkok, Thailand between January and August
      2005 was conducted. Studied subjects had a median age of 40 years with a median
      duration of taking PIs of 22.1 months. The mean serum total cholesterol (TC),
      high density lipoprotein cholesterol (HDL-c), low density lipoprotein cholesterol
      (LDL-c), and triglyceride (TG) levels were 259.7, 43.7, 135.2, and 506.8 mg/dl,
      respectively, and the mean TC:HDL-c ratio = 6.4. According to the US National
      Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III)
      guidelines, high TC, low HDL-c, high TC:HDL-c ratio, high LDL-c, and high TG were
      found in 52.4, 36.5, 18.8, 44.1, and 42.9%, respectively. Seventy-five subjects
      (44.1%) were taking lipid-lowering drugs. Only 54 subjects (31.8%) had baseline
      serum lipid profiles tested before beginning PI. There was statistically
      significant association between group of PI with serum TC and TG. Subjects taking
      double boosted and single boosted PI had significantly higher serum TC and TG
      levels than unboosted PI. Males had significantly higher serum TG levels, while
      females had significantly higher serum HDL-c levels. Age was significantly
      associated with serum TC, LDL-c levels, and TC:HDL-c ratios. Serum TC and LDL-c
      levels were also significantly higher in subjects taking efavirenz.

PMID- 17539250
TI  - Methylene blue staining of gastric tissue for the identification of Helicobacter
      pylori.
AB  - This study compared Giemsa (GM) and methylene blue (MB) stains for the diagnosis
      of Helicobacter pylori. Gastric biopsy specimens obtained from January 2001 to
      December 2005 were reviewed. They were all stained with hematoxylin and eosin, GM
      and MB stains. The slides were examined on a blinded basis. Direct comparisons
      were made between the both stains. Two hundred thirty-six cases were studied with
      a concordance rate of 98.3% (Kappa value = 0.951, p < 0.05), showing good
      agreement. MB stain can be substituted for GM stain, and is preferred because it
      is cost-effective, less time-consuming, less complicated to perform, accurate and
      widely available. Useful hints to reduce false negativity with MB stain are
      discussed.

PMID- 17539251
TI  - Detection of Escherichia coli O157: H7 vt and rfb(O157) by multiplex polymerase
      chain reaction.
AB  - A rapid method for detection of Escherichia coli O157: H7 using multiplex PCR was
      developed. Two oligonucleotide primer pairs were used for simultaneously
      detection of vt encoding verotoxin genes for virulence factor and rfb(O157)
      encoding the O-antigen specific for E. coli O157: H7. Multiplex PCR generated two
      products of 215 bp and 420 bp for vt and rfb(O157), respectively. Multiplex PCR
      detected reference strain O157: H7 (NF-7777) with a sensitivity of 10(5) CFU per
      ml with no amplification of other 15 pathogenic bacteria. After incubation of
      10(2) CFU/25 gram raw meat in tryptic soy broth at 37 degrees C for 8 hours,
      multiplex PCR conducted with the addition of 100 mg bovine serum albumin produced
      the two specific PCR products for E. coli O157: H7. This modified multiplex PCR
      is a rapid, sensitive, and specific technique for detecting and differentiating
      E. coli O157: H7 and has the potential to be used as an alternative to
      conventional methods for the screening of O157: H7 strains isolated from raw
      meat.

PMID- 17539252
TI  - Patient and sample-related factors that effect the success of in vitro isolation
      of Orientia tsutsugamushi.
AB  - Orientia tsutsugamushi is the causative agent of scrub typhus infection, a major
      cause of human disease in rural areas of Southeast Asia. Twenty-six blood samples
      collected from patients with serologically proven scrub typhus during a six month
      period were sent to Bangkok (535 km from the clinical site) by road at ambient
      temperature (average daily temperature range: 27.1-29.1 degrees C) for attempted
      in vitro isolation in Vero cells. O. tsutsugamushi was isolated from 12 samples
      (sensitivity 46.7%) with the time to isolation ranging from 16 to 37 days [median
      27 days, inter-quartile range (IQR) 22.5-33.5 days]. Patient factors such as days
      of fever and O. tsutsugamushi IgM antibody titer, transport factors such as
      transit time, and isolate genotype (Karp and Gilliam/Kawasaki) were assessed to
      determine their influence on the outcome of in vitro isolation. None of the
      factors significantly influenced the isolation outcome. This study demonstrates
      that O. tsutsugamushi can often be isolated in vitro from the blood of scrub
      typhus patients when transported at ambient tropical temperatures for many days.

PMID- 17539253
TI  - Identification of clinical isolates of Leptospira spp by pulsed field gel
      electrophoresis and microscopic agglutination test.
AB  - Twenty-five clinical isolates of Leptospira spp were characterized by microscopic
      agglutination test (MAT) and pulsed field gel-electrophoresis (PFGE) in
      comparison with 23 reference Leptospira serovars and with the saprophytic L.
      biflexa serovar Patoc. PFGE DNA profiling was more specific and reliable than
      MAT.

PMID- 17539254
TI  - Study of drug resistant cases among new pulmonary tuberculosis patients attending
      a tuberculosis center, Yangon, Myanmar.
AB  - A cross-sectional descriptive study was carried out at a tuberculosis center,
      Yangon, Myanmar from October 2003 to July 2004 to analyze the drug susceptibility
      of new sputum smear positive pulmonary tuberculosis patients. A total of 202
      Mycobacterium tuberculosis isolates were tested for resistance to isoniazid,
      streptomycin, rifampicin and ethambutol. Resistance to at least one anti
      tuberculosis drug was documented in 32 (15.8%) isolates. Monoresistance
      (resistance to one drug) was noted in 15 (7.4%) isolates and poly-resistance
      (resistance to two or more drugs) was noted in 17 (9.4%) isolates, including 8
      (4.0%) multi-drug resistant isolates (resistance to at least isoniazid and
      rifampicin). Total resistance to individual anti-tuberculosis drugs were:
      isoniazid (29, 14.3%), streptomycin (11, 5.4%), rifampicin (10, 4.9%) and
      ethambutol (1, 0.5%). The demographic data and possible contributing factors of
      drug resistance were evaluated among the drug resistant patients. Poly-resistant
      cases had significantly longer intervals between symptom appearance and achieving
      effective anti-tuberculosis treatment than mono-resistant cases (p = 0.015).

PMID- 17539255
TI  - A simple method to differentiate between Mycobacterium tuberculosis and non
      tuberculous mycobacteria directly on clinical specimens.
AB  - We report the applicability of testing susceptibility to paranitrobenzoic acid
      (PNB) directly on clinical samples as a rapid screening assay, to detect M.
      tuberculosis and differentiate it from non-tuberculous mycobacteria (NTM). One
      hundred smear positive sputum samples from patients with pulmonary tuberculosis
      attending the Department of Respiratory Medicine at VP Chest Institute, Delhi,
      were cultured on Lowenstein Jensen medium with and without 0.5 mg/ml
      paranitrobenzoic acid. Serial concentrations of known cultures of H37Rv, M.
      fortuitum, M. scrofulaceum and M. avium were used as controls in the study. After
      3 weeks of incubation, growth was observed on all the drug free Lowenstein Jensen
      slants but none of the slants containing PNB, which inhibited the growth of M.
      tuberculosis. The cultures were further confirmed to be M. tuberculosis by
      niacin, nitrate and catalase tests. Direct susceptibility to PNB was thus found
      to be a simple, cheap and technically feasible method of preliminary
      identification of M. tuberculosis and its effective differentiation from NTM,
      which may be adapted for use at Level II laboratories, especially in developing
      countries.

PMID- 17539256
TI  - High mast cell density associated with granulomatous formation in tuberculous
      lymphadenitis.
AB  - Mast cells are one of the main inflammatory cells involved in the pathogenesis of
      tuberculosis. Previous reports revealed that mast cells participated in both
      acute and chronic states of infection with Mycobacterium tuberculosis through
      direct contact or indirect enhancement by releasing mediators. The authors
      evaluated mast cell density on tissue sections of tuberculous lymphadenitis
      stained with 0.1% toluidine blue from 45 cases, all of which were retrieved from
      the surgical pathology files of King Chulalongkorn Memorial Hospital from 1999 to
      2006. A number of mast cells were correlated semiquantitatively with granulomas
      which were formed by aggregation of epithelioid histiocytes, multinucleated giant
      cells, and caseous necrosis. We found that mast cell density was significantly
      increased in lymph nodes with greater granuloma involvement (p = 0.030) and
      multinucleated giant cell formation (p = 0.010). These findings indicate a
      significant correlation between mast cell density and the granulomatous formation
      responsible for M. tuberculosis.

PMID- 17539257
TI  - Malnutrition and infectious disease morbidity among children missed by the
      childhood immunization program in Indonesia.
AB  - Although it has been thought that child immunization programs may miss the
      children who are in greatest need, there are little published quantitative data
      to support this idea. We sought to characterize malnutrition and morbidity among
      children who are missed by the childhood immunization program in Indonesia.
      Vaccination and morbidity histories, anthropometry, and other data were collected
      for 286,500 children, aged 12-59 months, in rural Indonesia. Seventy-three point
      nine percent of children received complete immunizations (3 doses of diphtheria
      pertussis-tetanus, 3 doses of oral poliovirus, and measles), 16.8% had partial
      coverage (1-6 of 7 vaccine doses), and 9.3% received no vaccines. Of children
      with complete, partial, and no immunization coverage, respectively, the
      prevalence of severe underweight (weight-for-age Z score < -3) was 5.4, 9.9, and
      12.6%, severe stunting (height-for-age Z score < -3) was 10.2, 16.2, and 21.5%,
      and current diarrhea was 3.8, 7.3, and 8.6% (all p < 0.0001), respectively. In
      families where the child had complete, partial, and no immunizations, the history
      of infant mortality was 6.4, 11.4, and 16.5%, and under-five child mortality was
      7.3, 13.4, and 19.2% (both p < 0.0001). Expanded programmatic coverage is needed
      to reach children who are missed by childhood immunizations in rural Indonesia,
      as missed children are at higher risk of morbidity and mortality.

PMID- 17539258
TI  - Beriberi outbreak among commercial fishermen, Thailand 2005.
AB  - In April 2005, The Tahi Bureau of Epidemiology investigated a reported outbreak
      of beriberi among commercial fishermen in Maha Chai, a port city in the Gulf of
      Thailand. The objective of this study was to verify the diagnosis of beriberi in
      affected individuals, describe the possible outbreak, ascertain risk factors, and
      provide prevention and control measures. We interviewed ill persons and treating
      doctors, and reviewed medical records to conduct a descriptive study. A probable
      case was defined as a crewmember of Ship A with one of the following: leg edema
      scrotal edema or ascites, dyspnea, chest discomfort, chest pain, extremity
      numbness, or extremity weakness. Confirmed cases were those with clinical
      criteria and laboratory findings consistent with thiamine deficiency. The
      outbreak started in early March, 2005 and continued until March 31, 2005. Ship A
      had 28 crewmembers (four Thai, 24 Myanmar). Overall, there were 15 probable cases
      (attack rate 53.6%, with three confirmed and 12 probable cases). Only three were
      tested for Vitamin B1 deficiency. All cases were male, with a median age of 28
      years (range 20-45). Fourteen of the 15 cases were Myanmar and one Thai. Due to
      limited resources, the crew ate only seafood and polished rice for almost two
      months prior to symptoms. Symptoms included edema (60%), chest discomfort (54%),
      and dyspnea (27%). Two persons died while on board the ship (case fatality 13%).
      The total time at sea for Ship A was 18 months, including a five-month delay in
      docking due to licensing problems.

PMID- 17539259
TI  - Overexpression of p53 and neoplastic cell proliferation in undifferentiated
      nasopharyngeal carcinoma.
AB  - Abstract. The author investigated the p53 status in correlation with cellular
      proliferation in the undifferentiated subgroup, which is infrequently found in
      caucasians. The author evaluated formalin-fixed, paraffin embedded tissue blocks
      from sixty cases with undifferentiated carcinoma of the nasopharynx by p53 and
      Ki67 immunostaining. All samples were retrieved from the surgical pathology file
      at King Chulalongkorn Memorial Hospital from 2001-2005. The patients had a mean
      age of 47 years. Stage IV was the most common stage, found in 21 cases (35%).
      Forty-four tumors (73%) overexpressed p53 protein, which was significantly
      associated with high rate of tumor cell proliferation (r = 0.477, p < 0.001). The
      higher the amount of p53 stained, the higher the rate of tumor cell
      proliferation. However, there was no statistically significant association
      between p53 protein overexpression and clinical status, including tumor volume,
      nodal status, and metastatic condition. This observation may explain why some
      tumors are resistant to radiation and are poorly controlled when they recur in
      distant organs.

PMID- 17539260
TI  - Obstetric outcomes in nulliparous young adolescents.
AB  - The objective of this study was to determine whether pregnant young adolescents
      under 15 years of age developed more obstetric complications than adult women. A
      retrospective case control study was undertaken. The pregnancies of 121
      nulliparous women under age 15 delivered at Department of Obstetrics and
      Gynecology, Faculty of Medicine, Chulalongkorn University between January 1994
      and December 2004 were compared to 121 nulliparous controls age 20-29. Multiple
      gestations were excluded. Young adolescents were more likely to develop anemia,
      preterm delivery, preeclampsia and deliver low birth weight neonates. More cases
      in the young adolescent group did not have antenatal care. Cephalopelvic
      disproportion occurred less often in the young adolescent group. No differences
      were observed between the groups regarding the prevalence of premature rupture of
      membranes, cesarean section, low Apgar score and fetal demise. Adolescents under
      15 years of age experienced more obstetric complications than adult women.
      Development of appropriate education, pregnancy prevention and antenatal care
      programs is invaluable for adolescents. These programs should target young
      adolescents who are at increased risk for adverse pregnancy outcomes.

PMID- 17539261
TI  - Factors associated with alcohol consumption among upper secondary school
      students.
AB  - A cross-sectional study was conducted to explore factors associated with alcohol
      consumption among upper secondary school students in Nakhon Ratchasima Province.
      A multistage sampling technique was used for selecting 850 students from 6
      schools and subjects were classified into 2 groups according to hazardous alcohol
      drinking (yes=107, no=743) by the Alcohol Use Disorders Identification Test
      (AUDIT). Data were collected by questionnaire from August to September 2005.
      Descriptive statistics, the chi-square test and multiple logistic regression were
      used to analyze data. The results showed the percent of hazardous drinking was
      12.59. Most of the students were 5 < or =6 years old (51.41) and in the science
      program (52.68%). Univariate analysis revealed the socio-demographic factors of
      gender, grade point average (GPA), monthly expenditure, age, and educational
      level were significantly associated with alcohol drinking (p < 0.05). Sibling and
      peer alcohol intake were associated with hazardous alcohol consumption (p < 0
      .05). Multivariate analysis, after adjusting for age, educational level and
      gender, revealed only 3 factors associated with male alcohol consumption: peer
      usual alcohol intake (OR = 23.46, 95% CI= 7.29-75.43) and peer occasional alcohol
      intake (OR = 5.57, 95% CI = 2.02-15.31), GPA > 3.0 (OR = 0.29, 95% CI= 0.11
      0.73). Only 2 factors were associated with female alcohol drinking: peer usual
      alcohol intake (OR = 63.41, 95 CI= 9.24-435.31) and peer occasional alcohol
      intake (OR = 7.94, 95 CI= 1.89-33.43). As a result, peer groups and close friends
      should be considered carefully when attempting to reduce the risk of alcohol
      consumption.

PMID- 17539262
TI  - Sexual behaviors of alcohol drinkers and non-drinkers among adolescents and young
      adults in Nha Trang, Vietnam.
AB  - A cross-sectional quantitative survey was conducted during August to November
      2005 with 880 youths (16-24 years-old), including 412 males and 468 females in
      Nha Trang city, Vietnam. It aimed to examine the association between alcohol use
      and sexual behaviors by gender difference. The data revealed that the majority of
      respondents (65.9%) had consumed alcohol, 25.8% had sexual touching with boy/girl
      friends, and 10.1% of respondents had engaged in sexual experiences including
      vaginal sex, anal sex, and/or oral sex. Young men were significantly more likely
      to drink than young women were (p < 0.001), and alcohol use was significantly
      associated with engagement in sexual experiences (p < 0.001). There was a strong
      significant different between sexual touching and alcohol drinking among males (p
      < 0.001) and females (p < 0.001). Forty percent of young men who did not use
      condom in last sex and 45% of young men who had multiple sex partners were
      drinkers compared to 4.8% and 1.6% of non-drinkers, respectively. These
      significant findings will be baseline data for integrating and adapting into
      intervention programs for alcohol and HIV among Vietnamese youth.

PMID- 17539263
TI  - Traditional Bhutanese medicine (gSo-BA Rig-PA): an integrated part of the formal
      health care services.
AB  - Traditional medicine in Bhutan is known as gSo-ba Rig-pa and is one of the oldest
      surviving medical traditions in the world. Other medical systems, such as Chinese
      medicine, Indian Ayurvedic medicine, Unani medicine, Greco-Roman medicine and the
      country's rich cultures and traditions have greatly influenced the way
      traditional Bhutanese medicine evolved. However, Buddhist philosophy remains the
      mainstream of this medical system. gSo-ba Rig-pa's principles are based on the
      perception the human body is composed of three main elements: rLung ('Air'),
      mKhris-pa ('Bile') and Bad-kan ('Phlegm'). When these three elements are balanced
      in the body a person is said to be healthy. The pathophysiology is also different
      from other medical systems, and the close link to Buddhism is reflected in the
      spiritual dimensions and the perception that all suffering is caused by
      ignorance. The treatment of diseases includes behavioral modification,
      physiotherapy, herbal medicines, minor surgery and spiritual healing. This makes
      the traditional Bhutanese medicine a unique and holistic health care system. The
      traditional medicine is an integrated and recognized part of the formal health
      care services in Bhutan under the auspices of the Ministry of Health. The article
      highlights three main points which can be learned from the Bhutanese experience:
      (1) the strong tradition of herbal medicines within gSo-ba Rig-pa forms a unique
      opportunity to prospect for new leads for development of pharmaceuticals, (2) the
      availability of the traditional medicine along with biomedicine broadens the
      health care choices for patients, and (3) the experiences of integrating two
      conceptually very different health care systems within one ministry contains
      important managerial lessons to be learned.

PMID- 17539264
TI  - Health risk assessment of villagers who live near a lead mining area: a case
      study of Klity village, Kanchanaburi Province, Thailand.
AB  - This was a cross-sectional study aimed at assessing environmental lead exposure
      and its association with blood lead levels, teeth lead levels and IQ of the
      inhibitants who live near lead mining in Kanchanaburi Province, Thailand. Two
      hundred fifteen villagers from 6 villages participated in this study. Exposed and
      non-exposed villagers were asked to perform IQ tests based on Raven's Standard
      Progressive Matrices. Environmental, blood and tooth samples were collected and
      analyzed to determine an association with the IQ level. The results showed that
      soil, vegetables (mint, bitter gourd, Chinese watercress, basil and turmeric) and
      meat (fish and shellfish) had lead concentrations above the recommended standard.
      Each person in the exposed group had blood and tooth lead levels higher than 10
      microg/dl and 10 microg/g, respectively. The mean IQ of the exposed group was
      82.70 (p < 0.05). The blood and tooth levels in the non-exposed group were lower
      than 10 microg/dl and 10 microg/g, respectively. The mean IQ scores in the non
      exposed group was 96.14 (p < 0.05). The health risk in the low IQ score exposed
      group was 5.6 times more than the non-exposed group (p < 0.05). The IQ scores of
      the exposed group were significantly inversly associated with the blood lead and
      tooth lead levels (r = 0.397 and 0.129, respectively, p < 0.05). The children in
      this study who were exposed to environmental lead had an accumulation of lead in
      their bodies. This resulted in a great impact on intellectual development. The
      results reveal that blood lead levels are the best predictor of lead exposure,
      and the tooth lead levels may provide epidemiological evidence for chronic
      toxicity. Populations with blood lead or tooth lead levels higher than normal
      limit should be treated with chelation therapy and health education.

PMID- 17539265
TI  - The successes and challenges of the IMCI training course in Lao Pdr.
AB  - The purpose of this article is to explore whether the style and content of the
      IMCI algorithm and delivery of the training course match the needs and capacities
      of the Lao health workers. Unlike other IMCI studies that rely on external
      indicators, this study uses an open-ended qualitative approach to focus on the
      perspectives of the trainees through observation and trainee interviews. The
      findings showed that IMCI is a practical tool for health workers, and the
      interactive course is an effective way to teach it. Health workers responded that
      learning the algorithm was challenging due to the novel format and guidelines,
      but easy due to its clarity and straightforwardness. The main problems concerned
      the adaptability of guidelines and shortage of time. Incorporating in-depth
      clinical explanations and inviting facilitators with medical knowledge and
      experience using IMCI may be key to resolving such issues.

PMID- 17539266
TI  - Training of nurses in ear examination and hearing screening in the school
      setting.
AB  - The objectives of this study were to determine the agreement between the ear
      examination findings of the otorhinolaryngologist (trainer) and the elementary
      school nurse (trainee) after training with the use of a penlight and to determine
      the mean sound pressure level (SPL) produced by school nurses as a standard
      parameter for hearing screening using a 512 tuning fork after training on tuning
      fork testing by the otorhinolaryngologist. Training workshops in ear examination
      using a penlight and hearing screening using a 512 tuning fork were conducted for
      school nurses. Data for assessment of ear examination skills and production of
      SPL were collected by questionnaire and observation of performance. Kappa
      statistics were used to assess agreement between trainees' and trainer's
      responses. Mean and standard deviation were determined for the assessment of the
      SPL produced. Results showed an excellent agreement between the school nurses'
      and otorhinolaryngologist's observations on ear examination. These included
      observations of the ear canal, visualization of the tympanic membrane and
      identification of unusual findings such as wax and discharge. The majority of
      nurses responded positively in terms of the ease and confidence in performance of
      the procedure. Regarding tuning fork testing, the nurses were able to produce
      significant SPL. The mean SPL produced by the nurses using a 512 tuning fork was
      56.316 dB.

PMID- 17539267
TI  - Dengue infections and pregnancy: caution in interpreting high rates of premature
      deliveries and maternal mortality.

PMID- 17539268
TI  - Pharmacokinetics of mefloquine with dihydroartemisinin as 2-day regimens in
      patients with uncomplicated falciparum malaria.
AB  - The objective of this study was to investigate the pharmacokinetics of mefloquine
      (MQ) when given as 750 mg at two different times in combination regimens with
      dihydroartemisinin (DHA) in patients with acute uncomplicated falciparum malaria.
      A total of 12 Vietnamese patients (6 in each group) were randomized to receive
      two MQ-DHA regimens as follows: regimen-A: an initial oral dose of 300 mg DHA,
      followed by 750 mg MQ and 300 DHA 6 and 24 hours later; regimen-B: an initial
      dose of 300 mg DHA, followed by 300 mg DHA and 750 mg MQ at 24 hours. Both
      combination regimens were well tolerated. All patients responded well to
      treatment with no recrudescence during a 42 day follow-up period. The
      pharmacokinetics of MQ following both regimens were similar but pooled data from
      both groups suggest that the kinetics of MQ was different from that observed in
      Vietnamese healthy subjects reported in a previous study. The median (95% CI)
      time period for maintenance of whole blood MQ concentrations above 500 ng/ml was
      16 (0-24) days. It was concluded that since no pharmacokinetic drug interaction
      was observed, MQ dose given 24 hours after an initial dose of DHA is a preferable
      combination treatment regimen with regard to patient compliance.

PMID- 17539269
TI  - Evaluation by villagers of the malaria control project on Lombok and Sumbawa
      Islands, west Nusa Tenggara Province, Indonesia.
AB  - The cooperative malaria control project between Indonesian and Japanese
      institutions was conducted from 2001 to 2004 at small malaria endemic foci on
      Lombok and Sumbawa Islands. The aim of this research was to evaluate the effects
      of the project according to the opinions of the villagers. We conducted a KAP
      survey of a simple random sample of 300 householders on each island. The
      conclusion of the study was that the project reduced malaria incidence
      significantly on Lombok. However, the effects were not as clear on Sumbawa. Poor
      socio-economic status and lack of school education were important related
      factors. Therefore, health education, or behavioral change communication, was an
      essential component of malaria control.

PMID- 17539270
TI  - Immunohistochemical study of acute and chronic toxoplasmosis in experimentally
      infected mice.
AB  - Acute and chronic Toxoplasma infections were evaluated in mice using stage
      specific antibodies and immunocytochemistry. Mice with acute toxoplasmosis were
      less active, had erectile body hair and seldom took food or water resulting in
      weight loss. All mice died within 7 days post-inoculation. The
      immunohistochemical technique enhanced visualization of parasites allowing their
      distribution to be accurately followed. Following intraperitoneal infection,
      tachyzoites were initially identified on the surface of the liver and spleen.
      There was a rapid increase in the number of tachyzoites associated with invasion
      from the surrounding connective tissue into the organs with formation of
      inflammatory lesions in the liver. The focal inflammatory lesions showed
      increasing numbers of tachyzoites with the period post-inoculation. Similar
      increases in tachyzoites were observed for the spleen. In contrast, only a few
      individual tachyzoites were seen in the brain at the final time point. In chronic
      infections, the mice were asymptomatic but tissue cysts containing large numbers
      of bradyzoites were observed in all brains with the average number of 295 tissue
      cysts per half brain and the average cystic size of 46.02 +/- 5.08 microm. By
      histology and immunostaining, the tissue cysts were readily identifiable along
      with a mild inflammatory cell infiltration into the meninges and perivascular
      cuffing. Double immunocytochemical labelling confirmed the exclusive presence of
      tachyzoites during the acute phase and bradyzoites during the chronic phase.

PMID- 17539271
TI  - The potential usefulness of the modified Kato thick smear technique in the
      detection of intestinal sarcocystosis during field surveys.
AB  - A total of 479 stool specimens were collected from rural communities of Ubon
      Ratchathani Province, Thailand and examined by two techniques: the modified Kato
      thick smear and the direct smear. The prevalence of Opisthorchis viverrini
      (14.8%), hookworm (10.2%), Sarcocystis spp (4.6%), Taenia spp (2.9%),
      Strongyloides stercoralis (2.1%), Giardia lamblia (1.2%), Echinostoma spp (0.6%),
      Ascaris lumbricoides (0.4%), Entamoeba histolytica (0.2%), Chilomastix mesnili
      (0.2%) and Endolimax nana (0.2%) were determined. The morphology of the
      Sarcocystis spp sporocysts examined by both procedures looked similar and was
      found to be easily recognizable. Among these specimens, 22 cases (4.6%) were
      positive for Sarcocystis infection detected by the modified Kato technique,
      whereas only one case (0.2%) was detected by both techniques. These differences
      were found to be statistically significant (p < 0.05), indicating that the
      modified Kato technique was decidedly more sensitive than the direct smear
      procedure in identifying Sarcocystis infection. An epidemiological survey was
      conducted in Khon Kaen Province involving 1124 stool samples using the modified
      Kato technique. The greatest frequency was Opisthorchis viverrini at 32.0% while
      the second highest was Sarcocystis spp at 8.0%. The prevalences of hookworm,
      Echinostoma spp, Taenia spp, Trichuris trichiura and Enterobius vermicularis were
      2.7, 2.1, 1.0, 0.2 and 0.2%, respectively. Other than opisthorchiasis,
      northeastern Thailand may be an endemic area for sarcocystosis. This is the first
      report of the applicability and potential usefulness of the Kato thick smear
      technique for the diagnosis of Sarcocystis infection in a field survey.

PMID- 17539272
TI  - Syndrome of inappropriate secretion of antidiuretic hormone associated with
      strongyloidiasis.
AB  - We report a case of syndrome of inappropriate secretion of antidiuretic hormone
      (SIADH) with accompanying severe strongyloidiasis in a 52-year-old male. On
      admission, he showed drowsiness and emaciation with severe hyponatremia. We gave
      sodium (saline or salts) in an i.v. drip infusion and orally without improvement.
      A urinalysis and plasma osmotic pressure test indicated SIADH, therefore,
      treatment was changed to restrict his sodium intake. The hyponatremia gradually
      improved initially, but the appetite loss, nausea, and hyponatremia continued.
      Endoscopy revealed white patches on the stomach wall and histopathological
      examination revealed infestation of the mucosal epithelium with numerous
      Strongyloides stercoralis larvae. Ivermectin treatment was then initiated and the
      abdominal symptoms and hyponatremia gradually resolved. We carefully investigated
      the underlying cause of the SIADH, such as disease of the central nervous system,
      lung cancer, and other malignancies, but no abnormality or clear cause could be
      found. We concluded that the patient developed SIADH secondary to severe S.
      stercoralis infection.

PMID- 17539273
TI  - Canine parasitic zoonoses in Bangkok temples.
AB  - Fecal samples were collected from 204 humans and 229 dogs from 20 different
      temples in Bangkok, as well as communities in the surrounding temple ground
      areas. Human and dog stool samples were examined for intestinal parasites
      including Giardia using zinc sulfate flotation and microscopy. Hookworms were the
      most common parasite in dogs (58.1%) followed by Trichuris (20.5%), Isospora
      (10%), Giardia (7.9%), Toxocara (7.4%), Dipylidium caninum (4.4%) and Spirometra
      (3.1%). Blastocystis hominis (5.9%) was the most common parasite in humans
      followed by hookworms (3.4%), Giardia (2.5%), Strongyloides (2%) and
      Cryptosporidium (1.5%). All samples microscopy-positive for Giardia were
      genotyped. The majority of Giardia isolated from the dog population was placed in
      Assemblage A, followed by Assemblages D, B and C, respectively, while human
      isolates were placed in Assemblages A and B. Therefore, dogs in temple
      communities posed a potential zoonotic risk to humans for transmission of
      hookworms, Giardia (especially Assemblage A genotypes) and Toxocara canis.

PMID- 17539274
TI  - Comparative efficacy of Solanum xanthocarpum extracts alone and in combination
      with a synthetic pyrethroid, cypermethrin, against malaria vector, Anopheles
      stephensi.
AB  - With a goal of minimal application of environmentally hazardous chemical
      insecticides, the larvicidal activity of cypermethrin was studied alone and in
      combination with the root extract of Solanum xanthocarpum against anopheline
      larvae. Petroleum ether extract was observed to be the most toxic, with LC,, of
      1.41 and 0.93 ppm and LC90 of 16.94 and 8.48 ppm at 24 and 48 hours after
      application, respectively, followed by carbon tetrachloride and methanol
      extracts. The values for cypermethrin were an LC50 of 0.0369 ppm after 24 hours
      and 0.0096 ppm after 48 hours and LC90 of 0.0142 and 0.0091 ppm after 24 and 48
      hours, respectively. The ratios of cypermethrin and petroleum ether extracts
      tested were 1:1, 1:2 and 1:4. Of the various ratios tested, the cypermethrin and
      petroleum ether extract ratio of 1:1 was observed to be more efficient than the
      other combinations. From the individual efficacy of each constituent, synergism
      was noted. This is an ideal ecofriendly approach for the control of malaria
      vector, Anopheles stephensi.

PMID- 17539275
TI  - Efficacy of Bacillus thuringiensis israelensis, VectoBac WG and DT, formulations
      against dengue mosquito vectors in cement potable water jars in Cambodia.
AB  - This study reports the evaluation of Bacillus thuringiensis israelensis (Bti), a
      biological larvicide, in cement jars holding river, well and rain water. Two Bti
      formulations, VectoBac WG and VectoBac DT, were evaluated in a village in Phnom
      Penh. Thirty-one households with cement jars supporting the colonization of
      Ae.aegypti immatures were chosen. In each house 3 jars were aligned next to each
      another and filled with the same type of water. One of the 3 jars was treated
      with VectoBac WG at 0.4 g per 50 liters, a second jar was treated with VectoBac
      DT at 1 tablet per 50 liters, and a third jar was an untreated control (UTC). The
      jars were not covered, kept outdoors and not subjected to water exchange
      activity. The efficacy of VectoBac to control natural Ae.aegypti infestation was
      measured by Ae.aegypti pupae surveillance, conducted 3 days per week for 3 months
      post-treatment (June-September 2004). All pupae were removed, allowed to emerge
      in the Cambodia National Malaria Center insectarium and the emerged adults were
      identified and counted. The VectoBac treatments were more effective in river
      water, followed by well and rain water. The VectoBac treatments significantly
      reduced the pupae numbers for a minimum of 3 months in the river water and 2.5
      months in the well water (p < 0.05). In the rain water, the pupae densities in
      the VectoBac WG and DT treated jars were not significantly different from the
      untreated jars, although the treated jars yielded 2.0 to 5.2 fold less pupae,
      respectively, than in the untreated jars during the 3 months post-treatment. The
      efficacy of VectoBac WG to control Ae.aegypti was similar to the efficacy of
      VectoBac DT in the 3 water types (p > 0.05). It was also observed that VectoBac
      WG and DT were target specific, without any adverse effects on aquatic predatory
      insects common in well and rain water. VectoBac WG and DT were found to be easy
      to-use formulations, with no need to repackage them prior to use in the
      containers. The amounts of VectoBac WG and DT used were 12.5 fold less by weight
      than temephos (Abate 1.0% SG).

PMID- 17539276
TI  - Simulated field evaluation of the efficacy of two formulations of diflubenzuron,
      a chitin synthesis inhibitor against larvae of Aedes aegypti (L.) (Diptera:
      Culicidae) in water-storage containers.
AB  - Tablet (40 mg a.i./tablet) and granular (2% a.i.) formulations of diflubenzuron,
      a chitin synthesis inhibitor, insect growth regulator, were evaluated for
      larvicidal efficacy against the larvae of Aedes aegypti (L.) in water-storage
      containers under field conditions in Thailand. Each formulation was applied to
      200-1 clay jars at 5 different dosages (0.02, 0.05, 0.1, 0.5 and 1 mg/l a.i.).
      The jars were covered with solid celocrete sheets and placed in the shade under a
      roof. Another experiment was also carried out using 3 different dosages (0.1, 0.5
      and 1 mg/l) where half the water in each treated jar and the control was removed
      and refilled weekly. Each treatment was replicated four times. The treatments
      were challenged by adding 25 3rd instar larvae/jar weekly. Assessments were made
      of each treatment through emergence inhibition (%EI) by removing and counting
      pupal skins one week after larval addition. Using these assessment techniques, a
      high degree of larvicidal efficacy (96-100%EI) was achieved with 4 dosages (0.05,
      0.1, 0.5 and 1 mg/l) of both (tablet and granular) formulations for a period of
      23 weeks post-treatment. The efficacy of the lowest dosage (0.02 mg/l) of tablet
      and granular formulations lasted for 21 and 22 weeks post-treatment,
      respectively. Under the conditions of water removal and weekly refilling, a high
      degree of larvicidal efficacy (96-100%El) at the 3 dosages was obtained with the
      tablet formulation 18 to 21 weeks post-treatment, whereas the efficacy of the
      granular formulation persisted 15 to 23 weeks post-treatment depending on the
      dosage. This study clearly demonstrates a high level of residual activity with
      both formulations of diflubenzuron against larvae of Ae. aegypti in water-storage
      containers. Considering environmental factors and water-use conditions, it is
      likely that dosages of 0.05 to 0.1 mg a.i./l are effective dosages providing long
      lasting control for 3 to 4 months in the field.

PMID- 17539277
TI  - Seasonality and insecticide susceptibility of dengue vectors: an ovitrap based
      survey in a residential area of northern Sri Lanka.
AB  - With the backdrop of a high incidence of dengue in Jaffna District, Sri Lanka, an
      ovitrap based survey was carried out from May 2005 to April 2006 in a residential
      area to study the seasonality and insecticide susceptibility of Aedes aegypti and
      Ae. albopictus. Conventional ovitraps were placed inside and outside of 10
      randomly selected houses to collect indoor breeding and outdoor breeding Aedes
      mosquitoes; collections took place fortnightly. A total of 3075 Ae. aegypti and
      2665 Ae. albopictus were collected in outdoor ovitraps, whereas in indoor
      ovitraps a total of 2528 Ae. aegypti and 2002 Ae. albopictus were collected. The
      highest values for Aedes density and positive ovitrap percentage were recorded in
      January 2006. A seasonal shift was observed in the density of Ae. aegypti and Ae.
      albopictus. Ae aegypti density was high during and after the Northeast monsoon
      whilst Ae. albopictus was the dominant species during the onset of the Northeast
      monsoon. A significant association (p < 0.05) between Aedes density and rainfall
      was observed. The association of these two species to site, either indoors or
      outdoors, was not statistically significant (p > 0.05). Both the species were
      found to be highly resistant to 4% DDT and completely susceptible to 5%
      malathion. The high prevalence and the ability of both species to breed indoors
      and outdoors should be taken into account when formulating a dengue vector
      control program with community participation in the Jaffna District, Sri Lanka.

PMID- 17539278
TI  - A new densovirus isolated from the mosquito Toxorhynchites splendens (Wiedemann)
      (Diptera: Culicidae).
AB  - A new densovirus was isolated and characterized in laboratory strains of
      Toxorhynchites splendens. The virus was detected by polymerase chain reaction
      (PCR) from mosquitoes reared in our laboratory. PCR fragments from each mosquito
      were compared by single strand conformation polymorphism (SSCP) assay and found
      to be indistinguishable. Thus, it is likely the densoviruses from these
      mosquitoes contain homologous nucleotide sequences. The PCR fragment
      corresponding to a 451 bp densovirus structural gene segment from each of 5
      mosquitoes had 100% identical nucleotide sequences. Phylogenetic analysis of the
      structural gene sequence suggests the newly isolated densovirus is more closely
      related to Aedes aegypti densovirus (AaeDNV) than to Aedes albopictus densovirus
      (AalDNV). Analysis of offspring and predated larvae suggests that vertical and
      horizontal transmission are responsible for chronic infections in this laboratory
      strain of Toxorhynchites splendens. The virion DNA is 4.2 kb in size, is closely
      related to, but distinct from, known densoviruses in the genera Brevidensovirus
      and Contravirus. Thevirus is tentatively named Toxorhynchites splendens
      densovirus (TsDNV).

PMID- 17539279
TI  - Freshwater mollusks at designated areas in eleven provinces of Thailand according
      to the water resource development projects.
AB  - The study was conducted at 75 collecting loci in 15 districts of 11 provinces in
      Thailand during 1999-2004. A total of 12,079 live mollusks were collected, 11,874
      were snails and 205 were clams. The snails were comprised of 39 species and
      classified into 9 families: Ampullariidae, Bithyniidae, Buccinidae,
      Potamiopsidae, Stenothyridae, Thiaridae, Viviparidae, Planorbidae and Lymnaeidae.
      The clams were comprised of 14 species classified into 2 families: Amblemidae and
      Corbiculidae. Fifteen species were medically important snails: Pomacea
      canaliculata, Pila ampullacea, P. pesmei, P. polita, Bithynia (Digoniostoma)
      funiculata, B. (D.) siamensis goniomphalos, B. (D.) s. siamensis, Filopaludina
      (Siamopaludina) martensi martensi, F. (Filopaludina) sumatrensis polygramma,
      Melanoides tuberculata, Tarebia granifera, Helicorbis umbilicalis, Gyraulus
      convexiusculus, Indoplanorbis exustus and Radix rubiginosa. Of these 3 snail
      species harbored trematode cercariae. I. exustus harbored Echinostoma malayanum,
      Xiphidio and Schistosoma spindale, and R. rubiginosa and B. (D.) siamensis
      goniomphalos harbored Xiphidio and intestinal flukes, respectively.

PMID- 17539280
TI  - Studies on the morphology of cercariae obtained from freshwater snails at Erawan
      Waterfall, Erawan National Park, Thailand.
AB  - The morphology of cercariae of freshwater snails from Erawan Waterfall, Erawan
      National Park, Kanchanaburi Province was studied between December 2002 and August
      2003. The snail samples were collected by handpicking using a counts per unit of
      time sampling method. The cercariae, larva stage of a trematode, were
      investigated using the shedding method where they were categorized into three
      groups and six species. The first group, Pleurolophocercous cercariae, consists
      of Haplorchis pumillo (C1) and Stictodora tridactyla (C3). The second group,
      Furcocercous cercariae, consisted of Mesostephanus appendicalatus (C2),
      Transversotrema laruei (C6) and Cardicola alseae(C4). The third group, Xiphidio
      cercariae, has only one species which is Loxogenoides bicolor (C5). Out of 1163
      snails, only 62 were found to be infected by cercariae, equivalent to a 5.33%
      infection rate. The infections grouped by species of the cercariae are as
      follows: C, 22 (1.9%), C, 29 (2.5%), C2 1 (0.1%), C6 1 (0.1%), C4 6 (0.5%) and C5
      3 (0.3%). The freshwater snail samples consist of four species. From a total of
      1163 samples, there are 687 Melanoides jugicostis, 91 Tarebia granifera, 296
      Thiara scabra and 89 Melanoides tuberculata. Infections were found in 45 (6.5%),
      6 (6.6%), 1 (0.3%) and 10 (11.2%), respectively.

PMID- 17539281
TI  - HIV communication between husbands and wives: effects on husband HIV testing in
      northern Thailand.
AB  - In northern Thailand, where substantial male-to-female transmission of HIV has
      occurred in stable partnerships, the relationships between counseling,
      communication, and HIV-preventive behaviors in married couples have not been well
      studied. In a study of HIV incidence among women in northern Thailand, each
      participant was advised to learn her husband's HIV-infection status and was asked
      to bring him for an interview at the final 12-month follow-up visit. Of the 337
      men interviewed, 58% reported having ever had an HIV test. More men reported
      testing following their wives' enrollment: 12% in the year prior to enrollment vs
      22% during the 1-year study (p < 0.001). In the univariate analysis, men's HIV
      testing during the 6 months before being interviewed was associated with
      communication about HIV testing with their wife and extra marital sex with non
      FSW while married. Testing following their wife's request was the most common
      reason reported. Agreement between husband's and wife's reports was poor for most
      issues, such as whether HIV-related communication had occurred, but agreement as
      to whether the husband had ever been tested for HIV was relatively high (kappa =
      0.62). However, in the logistic regression analysis, only sex with non-FSW while
      married remained associated with HIV testing (p = 0.02). The results suggest a
      relationship between counseling, communication, and husband HIV testing. Better
      communication by couples may result in more effective use of HIV testing, which
      is already prevalent in this population, to prevent HIV transmission.

PMID- 17539282
TI  - Hard-to-reach populations in Japan.
AB  - The objective of this study was to assess the trends of sampling locations and
      methods of studying hard-to-reach populations conducted in Japan. We accessed a
      Japanese medical database on 30 September 2005 to review 5 study types of hard-to
      reach populations conducted in Japan: men who have sex with men, homeless, sex
      workers, undocumented migrants, and injecting drug users. We then categorized
      their sampling locations and methods. We found 298 articles on hard-to-reach
      populations published from 1983 to September 2005. Of the 285 studies sampled,
      approximately 92% were facility-based studies and the rest were community-based.
      This tendency was consistent in each subgroup; the majority of the studies were
      conducted among patients in medical facilities. Our study shows the majority of
      studies on hard-to-reach populations in Japan adopted a convenience sampling
      method and were facility-based. We suggest the utilization of comparatively valid
      techniques, such as time-location or respondent driven sampling to more clearly
      understand these populations.

PMID- 17539283
TI  - Program issues in delivering targeted STI services through the public sector in
      the Greater Mekong region.
AB  - This review discusses the delivery of targeted STI services for both female sex
      workers (FSWs) and other high-risk groups through the public sector in the
      Greater Mekong region. Vaginal discharge algorithms for the general population
      are also discussed. High STI rates that justify targeted interventions have been
      reported recently amongst FSW in Cambodia, Lao PDR and Vietnam. Such
      interventions need to take into account the different patterns of sex work in the
      three countries. In Cambodia, there are large numbers of brothel-based FSWs
      although this pattern is changing as more brothels are closed by the authorities.
      In Lao PDR, services targeted towards reducing the burden of HIV/STI in
      FSW/service women are probably best delivered through NGO-led clinics. In
      Vietnam, commune based district health centers appear to offer better services
      for FSW than STI clinics. Male clients of FSW are an important group to target,
      but reaching such a heterogeneous population is difficult. Provision of quality
      STI drugs to those places where men present with STI symptoms should be a
      priority. The optimal way to manage STIs in FSWs is still unclear in this region.
      Clinical and laboratory specialists are keen to promote laboratory tests for STIs
      but there is an over reliance on direct staining techniques. In areas with high
      STI prevalences, periodic presumptive treatment could offer an effective option
      to reduce STI levels in high-risk groups until syndromic management algorithms
      are evaluated for local use. Social patterns of sex work are changing continually
      and require close monitoring in the future so that services can be adapted to
      these changes.

PMID- 17539284
TI  - Intussusception in a private tertiary-care hospital, Bangkok, Thailand: a case
      series.
AB  - This was a retrospective case series study of patients with intussusception at a
      private tertiary-care hospital in Bangkok, Thailand. The computerized hospital
      records of all 94 children aged 0-14 years diagnosed with intussusception from
      2000 to 2005 were reviewed. About half (51.1%) were males, 23.4% were less than 1
      year old. Most (78.7%) were Thai nationals. The highest case frequency was in
      August (n=12, Poisson means = 7.8, 95% confidence interval 6.3-9.6). Of these,
      none had the classical triad of vomiting, colicky pain, and mucous bloody stools.
      Only 12.8% had fever; abdominal mass was detected in 4.3%, and 4.3% had increased
      bowel sounds, while 34.0% had no specific signs. The most frequent site of
      intussusception was the ileocolic (62.6%). Stool cultures for bacteria and stool
      for rotavirus antigen obtained in some cases revealed no significant findings. Of
      the cases, 10 (10.6%) had spontaneous reduction, 84 (89.4%) underwent barium
      enema intervention, 10 of the latter (11.9%) required further surgical
      intervention. There were no mortalities during the observation period. There were
      10 recurrent events in this series. The 7-day recurrence-free probability was
      84.9% (95% CI 49.2, 96.3%). This study provides baseline data regarding
      intussusception in Thailand which may be useful for future epidemiological and/or
      clinical studies.

PMID- 17539285
TI  - A comparative assessment of the antimicrobial effects of garlic (Allium sativum)
      and antibiotics on diarrheagenic organisms.
AB  - Antimicrobial sensitivity tests were carried out on Escherichia coli, Shigella
      sp, Salmonella sp, and Proteus mirabilis using standard procedures. Significant
      differences (p < 0.01) were seen in the effect of the antimicrobial agents
      (garlic, ciprofloxacin and ampicillin), and in the sensitivities of the microbial
      species (p < 0.01) to the antimicrobial agents were observed. The gram-negative
      diarrheagenic pathogens from the stool samples were highly sensitive to garlic,
      while ciprofloxacin (CPX) was most effective against E. coli. The differences
      were inferred to result from genetic differences among the organisms and
      differences in the modes of action of the antibiotics. No isolates were resistant
      to garlic, making it a promising antimicrobial agent. It appears that antibiotics
      that interfere with DNA and RNA syntheses, such as garlic does, could constitute
      an effective partner in the synergic effect of garlic currently being
      investigated worldwide.

PMID- 17539286
TI  - Detection of tdh and trh genes in Vibrio parahaemolyticus isolated from Corbicula
      moltkiana prime in West Sumatera, Indonesia.
AB  - The occurrence of Vibrio parahaemolyticus in raw Corbicula moltkiana Prime from
      Lake Singkarak and Pasar Raya Padang market and in cooked samples in West
      Sumatera, Indonesia, was studied. Thirteen raw and seven cooked bivalve samples
      were positive using CHROMAgar Vibrio medium. All 47 V parahaemolyticus isolates
      were positive for toxR gene but negative for trh. However, 36% (17/47) of V
      parahaemolyticus strains were positive for tdh gene. Antibiotic profiling showed
      that 76% and 38% of isolates from raw and cooked bivalves respectively were
      resistant to ampicillin. Using RAPD-PCR analysis, most of the strains were
      clustered according to their source of isolation but some of the strains from raw
      and cooked samples were clustered together. These results indicate that
      pathogenic V parahaemolyticus isolates are present in Corbicula moltkiana Prime
      in West Sumatera, Indonesia, suggesting that V parahaemolyticus may also be
      present in seafood in other regions of Indonesia.

PMID- 17539287
TI  - Helicobacter pylori cagA, vacA and iceA genotypes in northern Thai patients with
      gastric disease.
AB  - Helicobacterpylori, a common infectious bacterium, has been linked to chronic
      gastritis, peptic ulcer and gastric cancer. Gastric biopsy specimens were
      obtained from 58 northern Thai patients with gastritis, 28 with gastric ulcer, 45
      with duodenal ulcer and 4 with gastric cancer. cagA, vacA s1 and iceA gene was
      found in 88, 98, and 89% of the specimens, respectively. For vacA, the frequency
      of subtype s1a, s1c and combined sla and s1c was 40, 16, and 41%, respectively.
      The frequency of subtype s1a/m1 and s1a/s1c/m1 was 27 and 20%, respectively.
      Fifty-three patients (39%) were infected with multiple vacA genotypes but there
      was no association with clinical outcome. cagA positive and mixed vacA s1a and
      s1c strains were found in significantly more cases of duodenal ulcer than
      gastritis (p < 0.05). For iceA, subtype iceA1 reached a frequency of 60%, whereas
      subtype iceA2 was only 24%.

PMID- 17539288
TI  - Diagnostic utility of adenosine deaminase (ADA) activity in pleural fluid and
      serum of tuberculous and non-tuberculous respiratory disease patients.
AB  - Adenosine deaminase activity (ADA) was assayed in pleural fluid and serum of 42
      subjects with pleural effusion. Twenty-nine of them had TB pleural effusion and
      the remaining 13 had pleural effusion due to non-TB respiratory diseases. Serum
      adenosine deaminase activity were also measured in 32 pulmonary tuberculosis
      patients without pleural effusion and equal numbers of healthy controls without
      systemic diseases for comparative analysis. The patients attending the medicine
      out-patient department (MOPD) of the B. P. Koirala Institute of Health Sciences,
      Dharan, Nepal were taken as study subjects. Serum and pleural fluid ADA
      activities were assayed spectrophotometrically by the method of Guisti and
      Gallanti. The mean serum ADA activity was significantly increased in patients
      with tubercular pleural effusion (34.53 +/- 10.27 IU/l) compared to pulmonary
      tuberculosis patients without pleural effusion (26.54 +/- 4.76 IU/l), (p =
      0.004), those with non-TB respiratory disease (16.71 +/- 5.16 IU/l), (p = 0.0001)
      and healthy controls (15.53 +/- 4.4 IU/l) (p = 0.0001). The mean ADA in the
      pleural fluid of tubercular pleural effusion patients (90.29 +/- 54.80 IU/l) was
      significantly higher compared to those with non-TB respiratory disease (24.43 +/-
      9.28 IU/l) (p = 0.0001). Using the lowest cutoff value for enzyme activity in the
      serum of patients with TB pleural effusion (25 IU/l), a test sensitivity of
      72.41% and specificity of 81.53% were obtained. Using the lowest cutoff value for
      enzyme activity in pleural fluid of patients with TB pleural effusion (45 IU/l)
      the sensitivity and specificity for diagnosis were 76.10% and 100%, respectively.
      Therefore, the measurement of ADA in tubercular pleural effusion has a utility in
      the diagnosis of tuberculosis when other clinical and laboratory tests are
      negative.

PMID- 17539289
TI  - Cytokine production in NK and NKT cells from Mycobacterium tuberculosis infected
      patients.
AB  - Tuberculosis, a major health problem in developing countries, has re-emerged in
      recent years in many countries. While it is accepted that various lymphocyte
      subsets are important responses to mycobacterial infection, the roles of NK and
      NKT cells in producing cytokines are still unclear. Thus we have evaluated, in
      Mycobacterium tuberculosis infection, the frequency of cytokine producing cells
      by flow cytometry. Of 30 individuals examined, 17 had clinical evidence of
      pulmonary tuberculosis while the rest showed no evidence of infection. Patients
      had a significantly higher number of IFN-gamma and IL-4-producing T cells
      compared to control subjects, but the ratio of IFN-gamma to IL-4-producing T
      cells was similar in both groups. There were no differences between cytokine
      profiles of NK cells in patients and control subjects. A significant increase in
      the number of NKT cells was observed in patients. A striking finding was the
      higher frequency of IL-4-producing NKT cells compared to IFN-gamma-producing
      cells. Moreover, individual NKT cell produced both IFN-gamma and IL-4. The
      preferential type of Thl or Th2 cells is due to mycobacterial strain, type of
      antigen presenting cells and stage of disease, all of which can lead to different
      patterns of cytokine production by variety of lymphocyte subsets.

PMID- 17539290
TI  - Multiple mutations in katG and inhA identified in Thai isoniazid-resistant
      Mycobacterium tuberculosis isolates.
AB  - A total of 29 Thai multi-drug-resistant/isoniazid-resistant Mycobacterium
      tuberculosis isolates were analyzed for mutations in katG from codons 254 to 549,
      inhA promoter and inhA open reading frame by DNA sequencing and single strand
      conformation polymorphism. Twenty-five multi-drug resistant isolates exhibited
      single point mutations (17 isolates at Ser315Thr plus Arg463Leu, 1 at Thr308Pro
      plus Arg463Leu, 7 at either Ser315Thr or Arg463Leu) while the other 4 isoniazid
      resistant isolates had single point mutation only at Arg463Leu. Seven of 25 multi
      drug-resistant isolates [4 at C(-15)T, 1 at T(-8)C; 1 at C(-15)T plus Ser94Ala
      and 1 at Ile21Val] and 2 of 4 isoniazid-resistant isolates [1 at C(-15)T, 1 at C
      (-15)T plus Ile21Thr] had mutations in inhA promoter and open reading frame,
      while the other 20 isolates had no mutation at any position. No frame shift
      mutation was observed in any tested isolates. This is the first report of two
      mutations, Trp308Pro of katG and T (-8)C of inhA in Mycobacterium tuberculosis
      isolates.

PMID- 17539291
TI  - Random amplified polymorphic DNA typing and phylogeny of Pythium insidiosum
      clinical isolates in Thailand.
AB  - Forty-three Pythium insidiosum clinical isolates recovered from human pythiosis
      cases in Thailand were characterized by random amplified polymorphic DNA (RAPD)
      analysis. Three random oligonucleotide primers, OPW11, OPW12 and OPX13 generated
      39, 34 and 35 DNA patterns with high value of typeability (100%), reproducibility
      (98.5, 88.8 and 93.3%) and discriminatory power (0.83, 0.82 and 0.77),
      respectively. Using GelCompar software based on band similarity, the 43 clinical
      isolates of P. insidiosum could be arranged into 9, 13 and 11 clades using OPW11,
      OPW12 and OPX13, respectively and the combination of all three primers revealed
      36 RAPD patterns. Members in each RAPD pattern varied in both clinical forms
      and/or geographical locations. RAPD pattern 15 was found in 6 isolates, half of
      which were found in central region of Thailand. Isolates MCC15 and MCC16 isolated
      from different patients exhibited identical pattern with all three primers. Our
      results revealed high genetic heterogeneity among Pythium insidiosum isolates in
      Thailand. RAPD method should be appropriate for future epidemiological studies of
      P. insidiosum strains from patients and from natural habitats.

PMID- 17539292
TI  - Ethnic variations in paraoxonase1 polymorphism in the Malaysian population.
AB  - The role of high-density lipoprotein associated paraoxonase (PON) 1 in protection
      against oxidative stress associated with the development of complications in
      diabetes mellitus has been reported. Variations in the PON1 gene, 55LM and 192QR
      have been described in different populations. These variations are known to be
      risk factors for heart disease, especially the L and R alleles. We have
      investigated the prevalence of both polymorphisms in the Malaysian population
      comprising the three major ethnic groups: Malay, Chinese and Indian, using
      polymerase chain reaction followed by restriction endonuclease digestion. The
      results show the pooled frequencies of L and R alleles were 0.91 and 0.54,
      respectively, similar to those in the Asian region. The frequency of the M allele
      was higher in Indians (p < 0.05), whereas the R allele was higher in both the
      Chinese and Malays compared to Indians (p < 0.05), indicating ethnic group
      dependent genetic differences. The most common genotypic combination was LL/QR,
      followed by LL/RR. The genotype frequencies for the total Malaysian population
      showed a significant departure from Hardy-Weinberg equilibrium for the 55LM (p =
      0.013) but not the 192QR (p = 0.056) polymorphisms. A strong linkage
      disequilibrium between L/55 and R/192 alleles was also observed. In the Malaysian
      population as a whole, Malays and Chinese showed a higher frequency of the R
      allele which is a risk factor for cardiovascular diseases.

PMID- 17539293
TI  - The reliability and validity of the Malay version of the 18-item audit of
      Diabetes Dependent Quality of Life (the Malay ADDQOL) questionnaire.
AB  - The objective of this study was to examine the reliability and validity of the
      Malay version of the 18-item Audit of Diabetes Dependent Quality of Life (the
      Malay ADDQOL). Patients with type 2 diabetes mellitus who fulfilled the inclusion
      criteria were systematically selected. The Malay ADDQOL linguistically validated
      from the 18-item English version ADDQOL was self-administered twice at a 1-week
      interval. Two hundred eighty-eight respondents were included in the study.
      Analysis involved checking the feasibility, floor and ceiling effects, internal
      consistency, test-retest reliability and factor analysis. Item means and standard
      deviations fulfilled the Likert scale assumptions. The Cronbach's alpha was 0.943
      (lower bound of the 95% CI of 0.935) and the intraclass correlation coefficient
      was 0.81 (95% CI from 0.72 to 0.87). Exploratory one factor analysis showed
      factor loadings above 0.5 for all the 18 items. The Malay ADDQOL has acceptable
      linguistic validity. It is feasible, has excellent reliability, content,
      construct validity, and is recommended to be used among Malay-speaking diabetic
      patients.

PMID- 17539294
TI  - [Pathogen identification of leaf-spot and its biological characteristics on
      Gentiana spp].
AB  - OBJECTIVE: To clear the pathogen of leaf-spot on (Gentiana spp. in Gansu
      province, and to control the disease theoretically. METHODS: The symptoms were
      obsersed and described in the field. The pathogen was identified on the base of
      morphology. The factors influencing the colony growth, myceliuim gross and
      sporulation were studied by the suspension and solid meedia. RESULTS: The
      pathogen was identified as Septoria gentionae. PDA and PSA were benefitial for
      colony growth and sporolation. The optimum temperature for colony growth,
      sporulation and mycelium gross were 25 degrees C. 20 degrees C and 20 degrees C
      respectively. The optimum pH was 7 for the pathogen growing and sporulation. 12h
      light plus l2 h dark, 8 hours UV plus 16 h light were beneficial to colony
      growing and sporulation. All-dark, 8 hours UV plus 16 hours dark were good for
      mycelium gross. Among 11 carbon sources, xylose, sucrose and soluble starch were
      very good for colony growth. Sucrose was best for sporulation, while raffilose
      best for mycelium gross. Among nitrogen sources, colony growth and sporulation
      quality reached highest on alanine, urea and NANO2 were not utilized very well.
      NH4H2PO4 was the best for sporulation and mycelium gross.

PMID- 17539295
TI  - [Antibacterial activity of water soluble fraction from Scolopendra subspinipes
      mutilans].
AB  - The water soluble fraction (SWSF) of centipede Scolopendra subspinipes mautilans,
      injected with Escherichia coli K12 D31 for 3-4 days showed broad-spectrum
      antimicrobial activity against Gram-positive, Gram-negative bacteria and fungi.
      It showed strong antibacterial activity against E. coli K12D31 at different
      temperatures, pH and ionic strengths. It did not show any hemolytic and
      agglutination activities at the concentration below 600 microg/ml. After E. coli
      K12 D31 treated with SWSF, the ultrastructure showed that its outer cell wall was
      broken, surface collapsed and intracellular substances leaked out.

PMID- 17539296
TI  - [Study on the volatile oil by SFE-CO, from crude and processed Rhizoma
      Atractylodis by GC-MS].
AB  - OBJECTIVE: To analyze the chemical constituents of the volatile oil by SFE-CO2
      from Rhizoma Atractylodis and its roasted products. METHODS: The chemical
      constituents of the volatile oil extracted by SFE-CO2 were separated and
      identified by GC-MS. RESULTS: 33 kinds of constituents were identified from
      Atractylodes lancea (Thunb.) DC. and its roasted products. The relative contents
      of 12 kinds of constituents from the processing products were descended and 7
      kinds were ascended; 30 kinds of constituents were identified from Atractylodes
      chinensis (DC.) Koidz. and its roasted products. The relative contents of 10
      kinds of constituents from the roasted products were descended and 11 kinds were
      ascended. CONCLUSION: In the processed products, the relative contents of some
      low boiling point constituents are descended but some high are ascended.

PMID- 17539297
TI  - [Determination of monotropein in Radix Morindae from different processed products
      by HPLC].
AB  - OBJECTIVE: To determine the contents of monotropein in the different processed
      Products of Radix Morindae. METHODS:  CONDITIONS: Kromasil C18 (150 mm x 4. 6
      mm,5 micorm) column; The mobile phase was methol-0.4% phosphate solution (5:95-
      >28.8: 71.2, 15 min); The velocity of flow was 1 ml/min; The detection wavelength
      was at 210 nm; And column temperature was 25 degrees C RESULTS: There were
      obvious differences between the crude and kinds of different processed products
      of monotropein in the Radix Morindae, The contents of monotropein from the
      different processed products (crude drugs, removed from wood, processed with
      salt, prepared) were 13.92 mg/g,9.10 mg/g, 9.21 mg/g, 12.86 mg/g, respectively.
      CONCLUSION: The different processing methods can make the contents of monotropein
      in the Radix Morindae.

PMID- 17539298
TI  - [Study on HPEC fingerprint of cultured Cordyceps militaris].
AB  - OBJECTIVE: To investigate the High Performance Capillary Electrophoresis (HPCE)
      fingerprint of cultured Cordyceps militaris (L.) Link. METHODS: Separation was
      performed on a 50 cm x 75 microm uncoated capillary with 0.5 mmol/L borate
      solution (pH 9. 18) as HPEC buffer. The run voltage was 20 Kv, temperature 25
      degrees C and the DAD detection was set at 254nm. RESULTS: Fingerprint consisted
      of 11 common peaks. The validation of methods was satisfied with the requirements
      for SFDA's technical regulations. CONCLUSION: The method was accurate and simple
      and suitable to the quality control of cultured Cordyceps militaris (L.) Link.

PMID- 17539299
TI  - [Studies on the chemical constituents from Inula cappa (II)].
AB  - OBJECTIVE: To study the chemical constituents of the root of Inula cappa. METHOD:
      The compounds were isolated and purified by recrystallization and chromatography
      with silica gel column and Sephadex LH-20 column. Their structures were
      identified by physico-chemical properties and spectral analysis. RESULTS: Seven
      compounds were isolated as scopolin (I), octacosanoic acid (II), tritriacontane
      (III), (2S,3S,4R,8E)-2-[(2'R)-2'-hydroxydocosanosylamino]-octadecane-1,3,4
      triol(IV),(2S,3S,4R,8E)-2-[(2'R)-2'-hydroxytricosanosylamino]-octadecane-1,3,4
      triol(V), (2S,3S,4R,8E)-2-[(2'R)-2'-hydroxytetracosanosylamino]-octadecane-1,3,4
      triol(VI), (2S,3S,4R,8E)-2-[(2'R)-2'-hydroxypentacosanosylamino]-octadecane-1,3,4
      triol(VIII), (2S,3S,4R,8E)-2-[(2'R)-2'-hydroxyhexacosanosylamino]-octadecane
      1,3,4-triol(VIII). CONCLUSION: All compounds were isolated from Inula cappa for
      the first time.

PMID- 17539300
TI  - [Study on the active components of Nardostachys chinensis].
AB  - To study on the active components of Nardostachys chinensis Batal, the compounds
      were isolated and purified by chromatographic methods, with their structures
      identified by spectral analysis and comparison with published data. 9 compounds
      were obtained and their structures were identified as acaciin, ursolie acid,
      octacosanol, kanshone A, nardosinonediol, nardosinone, aristolen-9beta-ol,
      oleanolic acid and beta-sitosterol. Acaciin, ursolie acid and octacosanol were
      obtained from Nardostachys chinensis Batal. for the first time. Acaciin and
      ursolie are the active components of antihiotics and anti-inflammatory.

PMID- 17539301
TI  - [Studies on the chemical constituents of the aerial parts of Seseli mairei].
AB  - OBJECTIVE: To study the chemical constituents of the aerial parts of Seseli
      mairei Wolf. METHODS: The chemical constituents have been separated with manifold
      chromatography methods, and their structures were determined hy spectral
      analysis. RESULTS: Thirteen compounds were isolated and identified as sphondin
      (I), hergapten (II), isopimpinellin (III), umbelliferone (IV), chrysosptertin B
      (V), apiin (VI), rutin (VII), quercetin (VIII), ferulic acid (IX), falcarindiol
      (X), docosanol (XI), beta-sitosterol (XII), daucosterol (X III). CONCLUSION: All
      these compounds were isolated from the aerial parts of Seseli mairei Wolf. for
      the first time.

PMID- 17539302
TI  - [Studies on chemical components of Cirsium segestum].
AB  - Six chemical components were got from the alcohol extract of Cirsium segestum,
      their structures were identified by UV, IR, NMR, MS and EA. They were 5,7
      dihydroxyflavone, baicalin, oleanolic acid, cholesterol, methyl ursolate and
      rutin. The first to the fifth of which were got from Cirsium segestum for the
      first time.

PMID- 17539303
TI  - [Studies on the chemical constituents of Vaccinium iteophyllum].
AB  - 7 compounds were isolated from the ethyl-acetate extract of Vaccinium iteophyllum
      Hance by using repeated silical gel column chromatography. These 7 compounds were
      identified by means of physico-chemical propertic and spectroscopic analysis as
      beta-sitosterol (I), ursolic acid (II), taraxerol (III), taraxerone (IV),
      friedelin (V), friedelinol (VI), 19,24-dihydroxyurs-12-en-3-one-28-oic acid
      (VII). The chemical constituents from this plant were reported here for the first
      time.

PMID- 17539304
TI  - The study on the extraction method of indirubin from Indigo Naturalis.
AB  - OBJECTIVE: To discuss how to extract the indirubin of the higher purity from
      Indigo Naturalis. METHODS: After extracting the indirubin from Indigo Naturalis
      by acetic ether, compare the separation effect of the extract in Si gel column
      with that in alumina column. RESULTS: The indirubin in Indigo Naturalis by Si gel
      column chromatography is chosen. The purity of indirubin is 98.3% after Si gel
      column chromatography. CONCLUSION: The indiruhbin of the higher purity was
      attained by the simple experimental method.

PMID- 17539305
TI  - [A new method in determination of formononetin content in Trifolium pratense].
AB  - OBJECTIVE: A new method was established to determine the formononetin content in
      Trifoblium pratense L. METHODS: Effects of fluorescence intensity, as well as its
      precision, repetition and recovery efficency were studied. RESULTS: The linear
      relationship was y = 1440 x -0.263, r = 0.999, the detection limit was 1.50 x 10(
      9) mol/L, the relative deviation between this method and HPLC method was 1.65%.
      CONCLUSION: The study indicated that this method was viable, and could be used in
      both scientific research and industrial production.

PMID- 17539306
TI  - [Effect of kuijieling decoction on gene expression of TLR2, TLR4 in colonic
      mucosa of UC rats].
AB  - OBJECTIVE: To investigate the effect of Kuijieling Decoction (KD) on gene
      expression of Toll-like receptor (TLR) 2,4 in colonic mucosa of ulcerative
      colitis( UC) rats. METHODS: 48 rats were divided into six groups as follows:
      normal control (NC) group, model control (MC) group, Kuijieling low dose (KLD)
      group, Kuijieling medium dose (KMD) group, Kuijieling high dose (KHD) group and
      SASP group. TLR2/4 gene expression in colonic mucosa was measured by reverse
      transcription polymerase chain reaction (RT-PCR). RESULTS: Relative gene
      expression of TLR2/4 in MC group were significantly higher than that in NC group
      (P < 0.01). Relative gene expression of TLR2 in KMD and KHD group was
      significantly lower than that in MC group (P < 0.05). Relative gene expression of
      TLR4 in KHD group was significantly lower than that in MC group (P < 0.05).
      CONCLUSION: Up-regulation of TLR2 and TLR4 gene expression can be seen in colonic
      mucosa of UC rats. KD can inhibit the gene expression of TLR2 and TLR4. The
      inhibitory effects of KD on UC may be associated with the inhibition of TLR2 and
      TLR4 gene expression.

PMID- 17539307
TI  - [Study on the anticancer effects of extracts from roots of Livistona chinensis in
      vitro].
AB  - OBJECTIVE: To observe the effects of extracts from root of Livistona chinensis on
      the growth inhibition in seven carcinoma cell lines. METHODS: The growth
      inhibition was analyzed by MTT, cell colony and cell growth curve measuremen
      technique in the stomach carcinoma SGC7901, Lymphocytic leukemia L1210, Lymphoid
      neoplasm P388D1, tumor of cervix uteri Hela, hepar carcinoma hele 7404, melanoma
      B16 and mouse neuroblastomax rat glioma hybrid NG108-15 cells lines. RESULTS: The
      growth of all tumor cells were inhibited by ethyl acetate of alcohol extract from
      roots of Livistona chinensis. The growth of all tumor cells were not affected by
      low dose extracts (0.5 microg/ml). The growth of all tumor cells were obviously
      inhibited by higher dose extracts (5.0 microg/ml). The growth of all tumor cells
      were inhibited in growth curve measurement. CONCLUSION: The results show that
      ethyl acetate of alcohol extracts from roots Livistona chinensis possesses the
      role of antitumor in cell culture.

PMID- 17539308
TI  - [The extract of compound Radix Scutellariae on mRNA replication and IFN
      expression of influenza virus in mice].
AB  - OBJECTIVE: To study the extract of compound Radix Scutellariae on inhibiting the
      mRNA replication and inducing the INF expression of influenza virus in mice's
      vivo. METHODS: Influenza virus infected mice pneumono-adaption stock A/FM/1/47
      (H1N1) evoked mice pneumonia taken as animal model. RT-PCR was adopted to measure
      the content of influenza virus's mRNA and INF in mice to study the effect of the
      extract on mRNA replication and IFN expression. RESULTS: The extract of compound
      Radix Scutellariae could inhibit influenza virus' s mRNA replication (P < 0.01)
      and induce interferon expression in mice (P > 0.05). CONCLUSION: The extract of
      compound Radix Scutellariae can induce interferon and inhibit influenza virus
      replication in mice.

PMID- 17539309
TI  - [Effect of effective fractions and its compatibilities and proportions of xie-xin
      decoction on nitric oxide production in peritonea macrophages from rat].
AB  - OBJECTIVE: To observe the effect of effective fractions (Conjunct anthraquinone,
      free anthraquinone and total flavonoids) and its compatibilities and proportions
      of Xie-Xin decoction on NO production in peritonea macrophaes from rat. METHODS:
      Growth activity of macrophages cultured with different levels of active
      components were detected by MTT. NO concentrations in peritoneal macrophages
      induced by LPS were detected by Griess method. RESULTS: The NO production from
      macrophages induced by LPS was inhibited obviously by active components at the
      levels of 0.01-0.1 mg/ml. The best time of administration was 1 h induced by LPS.
      The inhibition of best proportions of compatibilities of Conjunct anthraquinone
      and total flavonoids, free anthraquinone and total flavonoids were stronger than
      effective fractions solo. CONCLUSION: The NO production is inhibited obviously by
      these effective fractions, especially by conjunct anthraquinone. Effective
      fractions can inhibit the function of activated macrophages.

PMID- 17539311
TI  - [Study on ultrasonic wave extraction of flavonoids from the bulb of Lilium
      lancifolium].
AB  - The extraction technology of flavonoids in the bulb of Lilium lancifolium Thunb.
      was studied by comparing the ultrasonic wave extraction technology with the
      traditional extraction technology. The results showed that the ultrasonic method
      was better. Also, the optimal procedure for the ultrasonic wave method were
      studied. Under the conditions of 1:30 of 80% ethanol to the bulb of Lilium
      lancifolium Thunb. weigh ratio, ultrasonic treatment for 40 min twice at the
      temperature of 70 degrees C, the average extraction rate of flavonoids was as
      high as 99.25%.

PMID- 17539310
TI  - [Optimization of preparation for matrine-loaded magnetic chitosan microspheres].
AB  - OBJECTIVE: To study the technique of preparation and optimization of magnetic
      chitosan microspheres. METHODS: Magnetic fluid was produced by co-precipitation
      method and magnetic chitosan microspheres were produced using a convenient method
      of ionic gelation. A global optimization algorithm was used to optimize the
      parameters. RESULTS: The formulated magenetic fluid and microspheres were
      characterized size and the size distribution. The average particle size of
      magnetic fluid and matrine-loaded chitosan magnetic microspheres were found to be
      152.2 nm and 682.4 nm. CONCLUSION: Global optimization algorithm is an efficient
      method to optimize the parameters.

PMID- 17539312
TI  - [Preparation and characterization of chitosan coated puerarin liposomes].
AB  - OBJECTIVE: To prepare chitosan coated puerarin liposomes and investigate their
      physicochemical properties. METHODS: Puerarin liposomes were prepared by reverse
      phase evaporation technique and then coated with chitosan. Using encapsulation
      efficiency as index of examination and designing an orthogonal experiment, the
      optimal formulation of liposomes was determined. The physicochemical properties
      of uncoatd and chitosan coated puerarin liposomes were investigated,
      respectively. RESULTS: Uncoated and chitosan coated puerarin liposomes were
      spherelike and smooth. The mean particles size of uncoated and coated liposomes
      were 217. 3nm and 632. 6nm, respectively. The Zeta potential were -14.44 mV and
      +35.61 mV, respectively. The encapsulating efficency was 50. 6% and 51.1%,
      respectively. CONCLUSION: Puerarin liposomes can be prepared by reverse phase
      evaporation technique successfully. The chitosan coated purarin liposomes ware
      spherelike and smooth.

PMID- 17539313
TI  - [Comparative study of extraction of corn stigma polysaccharide].
AB  - OBJECTIVE: To study enzyme treatment, transonic and a combination of the two
      processes for the extraction of corn stigma polysaccharide. METHODS: Enzyme and
      ultrasound-assisted extraction conditions were optimized respectively through
      orthogonal test. A combination of the two methods was investigated. RESULTS: The
      combined method was more efficient than the enzyme treatment and transonic
      individually. The enzyme-assisted process was in the medium level in compare of
      the other two. CONCLUSION: The combined method was the most favourable one.

PMID- 17539314
TI  - [Studies on optimal extraction conditions of flavonoid from the flowers of
      Edgeworthia chrysantha].
AB  - OBJECTIVE: To study the optimum extraction process of the total flavonoids from
      the flowers of Edgeworthia chrysantha Lindl. METHODS: The effect of the
      concentration of ethanol, extraction time and ratio of material to liquid on the
      total flavonoid contents were investigated by the orthonogal test with the
      content of tiliroside as the chemical reference. RESULTS: The optimum extraction
      condition was established as follows: the concentration of ethanol 75%,
      extraction time 1. 5 hours and the ratio of material to liquid 1:9. CONCLUSION:
      The method is simple and feasible, and is the optimum extraction process of the
      total flavonoids from flowers of Edgeworthia Chrysantha Lindl.

PMID- 17539315
TI  - [HPCE determination of matrine in matrine liposome].
AB  - OBJECTIVE: To establish an HPCE method for the determination of matrine in
      Matrine Liposome. METHODS: HPCE was used. The best condition was achieved with a
      fused silica capillary tube( 150 cm x 75 microm), 0.25 mol/L phosphate buffer (pH
      6.8), at constant voltage of 20 kV and temperature at 25 degrees C. The UV
      detection wavelength was 206 nm. RESULTS: The calibration curve was linear in the
      range of 0.3-6.025 mg/ml for matrine (0.9995). The average recovery of matrine
      was 97.3%. CONCLUSION: This methods is simple, quick, accurate and suitable for
      the quality control for Matrine Liposome.

PMID- 17539316
TI  - [Clinical research of isatis root eyedrops on the acute bacterial
      conjunctivitis].
AB  - OBJECTIVE: To evaluate the efficacy and safety of isatis root eyedrops on the
      acute bacterial conjunctivitis. METHODS: A randomized, double-blind and parallel
      study was conducted on 200 cases. Isatis root eyedrops and Hailun eyedrops
      (levofloxacin eyedrops), six times each day, were administered in test and
      control groups respectively. All patients have been observed for 7 days. The
      clinical effectiveness and reaction to drug after administration were assessed as
      the observation indexes. RESULTS: The efficacy rates in test and control group
      were 90% and 93%, repectively, the difference between the two groups had no
      statistic significance (P > 0.05). There have been two cases with side effects
      among the test and control groups respectively. CONCLUSION: Isatis root eyedrops
      have an excellent efficacy and safety on the acute bacterial conjunctivitis.

PMID- 17539317
TI  - [Prognostic factors of pregnancy in intrauterine insemination].
AB  - BACKGROUND: The artificial insemination is the introduction of spermatozoa in the
      feminine genital tract without carrying out sexual contact and with the purpose
      of obtaining the pregnancy. The insemination intrauterine has improved its rate
      of success thanks to the technological advances and the best knowledge of human
      reproductive physiology. OBJECTIVES: To evaluate the prognostic factors for the
      pregnancy success and calculate the cumulative rate per cycle in IUI
      (intrauterine insemination). PATIENTS AND METHODS: This study was descriptive,
      retrospective, analytic, and longitudinal. The cycles of IUI were analyzed from
      January 1st 2003 to December 31st 2005. Couples 24-41 years old with primary and
      secondary infertility were included. The following variables were studied: age of
      participant, type of infertility, length of infertility, aetiology,
      postcapacitation sperm density and motility, number of follicles, endometrial
      thickness, and the cycle number in which the IUI was performed. Patients carried
      out a protocol of ovarian stimulation and follicular follow up. The results were
      analyzed with 11.0 SPSS, continuous variables were analyzed and reported as means
      +/- SD with univariate logistic regression to determine statistic significance.
      Categoric variables were reported in frequencies and percentages. ROC curves were
      calculated to determine optimal cutting points. RESULTS: 668 cycles were analyzed
      in 391 couples. The pregnancy rate per cycle and couple was of 13.0 and 21.7%
      respectively. Means +/- SD patient age was 33.5 +/- 3.4 years old. The three
      variables with p < 0.05 were: the infertility duration, sperm motility and the
      cycle number in which IUI was performed. No statistical significance was found in
      the remaining variables. CONCLUSIONS: The greatest success in IUI will be
      achieved with infertility of 4 years or less, with sperm motility of 77.6% and in
      the first two cycles of treatment.

PMID- 17539318
TI  - [Perinatal results in pregnancies obtained with embryo transfer in vitro
      fertilization: a case-control study].
AB  - BACKGROUND: In 1978 the first successfull birth by in vitro fertilization took
      place and this assisted reproduction technique became alternative of treatment in
      the couples with infertility that had not obtained pregnancy with conventional
      treatments. The conditions of clinical treatment and laboratory improved, which
      were in greater number of pregnancies. In 1985 the first study was published that
      showed adverse perinatal results in pregnancies obtained with fertilization in
      vitro. Some researchers attributed these results to the increase in the number of
      multiple pregnancies, pregnant patients older than 35 years, and to the
      antecedents of infertility. OBJECTIVE: To compare the perinatal outcomes of
      pregnancies obtained by in vitro IVFET vs spontaneous pregnancies. PATIENTS AND
      METHODS: A retrospective, case-control study. All pregnancies obtained after IVF
      ET from October 1st 1999 to November 30th 2004 were compared with a control group
      of naturally conceived pregnancies and matched by maternal age and the number of
      fetus. Data concerning obstetric complications and perinatal outcomes were
      recorded and matched with their control. RESULTS: We analyzed 26 vs 52 singleton,
      10 vs 20 twins, 5 vs 5 triplet pregnancies, there were no controls for the
      quadruplet and quintuplet pregnancies. The mean gestational age at delivery and
      Capurro score in the singleton pregnancies were 37.8 vs 38.8 y 38.2 vs 39.4 weeks
      for the study and control groups respectively (p < 0.05), the female sex was more
      frequent in singleton pregnancies obtained by FIVTE (p < 0.05). There were no
      statistically significant difference in the premature rupture of membranes,
      preterm labor, preeclampsia, gestational diabetes, placenta accreta, preterm
      delivery and low birth weight. The mean birth weight of the pregnancies obtained
      by IVF were of 2,962.8, 2,100 and 1,532 g for singleton, twin, and triplet
      respectively. A higher incidence of preterm delivery was found in twin
      pregnancies but it was not statistically significant. CONCLUSIONS: The rates of
      adverse perinatal outcomes of the pregnancies after IVF were not higher than
      pregnancies conceived spontaneously. Twin pregnancies have a greater risk to
      cause preterm delivery not related to the IVFET procedure.

PMID- 17539319
TI  - [Early severe restriction of intrauterine growth: a therapeutic alternative].
AB  - It is presented the case of the second pregnancy of a 36 year-old patient with
      antecedent of preeclampsia that was solved, at full-term, with a Caesarean
      operation by means of which was obtained a healthy new born. The patient began
      her prenatal control at 29th week. Ultrasound made at her admittance showed a
      fetus with an approximated weight of 451 grams. The patient was hospitalized
      until completing protocol of study for restriction of severe fetal growth. At
      34.5 weeks, an ultrasonographical control showed an alteration in venous duct;
      for that reason it was decided to interrupt pregnancy abdominally. There were no
      surgical complications and was obtained a phenotypically normal new born, male,
      weight of 820 grams and size of 33 cm, who was referred to the Instituto Nacional
      de Perinatologia. At 43.3 weeks he was discharged from hospital with a weight of
      1,840 grams. At the present he's fed with fortified milk.

PMID- 17539320
TI  - [Diagnostic and frequency of fetal heart disease by echocardiography in
      pregnancies with high-risk factors].
AB  - BACKGROUND: Fetal heart diseases are increasingly frequent. These are part of
      birth defects and, therefore, appear in early phases of the gestation. Diagnosis
      or early detection of functional and structural abnormalities of the heart allows
      to the obstetrician and the pediatric cardiologist to plan, in a timely manner,
      the treatment and prenatal and postnatal monitoring with the purpose of
      preventing complications. OBJECTIVE: To determine the types and frequencies of
      heart diseases in pregnancies with high-risk factors. PATIENTS AND METHOD: It was
      analized an observational, descriptive and retrospective series of cases. From
      January 2003 to June 2006, fetal echocardiograms were made in women with
      pregnancies longer than 15 weeks and with high-risk factors. At childbirth was
      made a cardiovascular evaluation. Analysis was carried out through descriptive
      statistics. RESULTS: maternal age average was of 27.3 +/- 6.8 years; gestational
      age was of 31 +/- 5 weeks. In total, there were carried out 275 fetal
      echocardiograms (FE) in 208 patients; in 56 of them, was made one fetal
      ecocardiogram, two in 37 and three in 15. Risk factors of reference to the
      specialized medical unit were: abnormalities detected through obstetrical
      ultrasound (35.1%), tachycardia-bradycardia-arrhythmia (29.8%), probable
      chromosomic anomalies (13.9%), oligohydramnios or polyhydramnios (4.8%), familiar
      antecedents of congenital heart diseases (3.8%), others (12.6%). Heart disease
      was diagnosed by fetal echocardiogram in 55 patient (26.4%): unique ventricle (n
      = 5), hypoplastic right ventricle (n = 3), hypoplastic left ventricle (n = 4),
      congenital complete heart block (n = 1), Ebstein and dysplasia of the mitral and
      tricuspid valves (n = 12), tumor (n = 5), ectopia cordis (n = 2),
      auriculoventricular channel (= 1), supraventricular tachycardia (n = 4),
      supraventricular extrasystole (n = 3) and other. Diagnosis was confirmed at
      childbirth in 99.5% of the cases. The treatment was initiated in uterus for
      arrhythmia and cardiac insufficiency in 19 patients. The patients with high-risk
      cardiopathy (at birth) were evaluated at beginning through specialized
      cardiological treatment and then they were transferred to the service of
      pediatric cardiology. CONCLUSIONS: Frequency of fetal heart diseases in patients
      with high-risk factors is of 25.4%. In these patients, the fetal echocardiogram
      (prenatal and postnatal) allows planning the optimal cardiological and obstetric
      treatment as well as to inform to the relatives.

PMID- 17539321
TI  - [Development and validation of an in vitro culture model for the study of the
      differentiation of human trophoblast].
AB  - OBJECTIVES: To develop a method to isolate cells of human citotrophoblast and to
      assess its invading and differentiation capacity. TYPE OF STUDY: Experimental
      biomedical. MATERIALS AND METHOD: Citotrophoblasts of healthy placentas of full
      term pregnancies were isolated by digestion with dispase and purification in a
      density gradient. The purity by immunoreactivity to citokeratin 7 and the
      invasiveness of the cells of citotrophoblast in Matrigel were evaluated. The
      enzymatic activity was determined through zimography and hCG secreted was
      quantified by means of ELISA. The expression of alpha 1 and alpha 5 integrins was
      evaluated by immunohistochemistry. RESULTS: Citotrophoblasts with a purity of 97%
      were obtained; they differentiated themselves, in a spontaneous way, to a
      syncytium after four days. There was a growing production of hCG. Maximum
      invasiveness of citotrophoblasts ocurred the first two days, when their phenotype
      was mononuclear and coincided with the secretion of pro-MMP-9, and then it
      diminished according with the culture time. Immunoreactivity to the alpha 1 and
      alpha 5 integrins was observed in citotrophoblast cells with mononuclear
      phenotype. This immunoreactivity was lower in cells with phenotype of syncytium.
      CONCLUSIONS: It was created an in vitro model that replicates events of the early
      development of the placenta. These events resemble the invasion and
      differentiation phase of the citotrophoblast. This model has potential utility in
      the study of the mechanisms of damage in preeclampsia.

PMID- 17539322
TI  - [Assessment of a microarray of solid-phase antibodies to the study of chemokines
      secreted by the chorioamniotic membrane].
AB  - OBJECTIVE: At the end of pregnancy, a complex signaling network of cytokines,
      chemokines and proteic effector molecules is started. Due to such complexity,
      this network is very difficult to analyze. The aim of the present study was to
      evaluate the effectiveness of an antibody-based proteomic analysis method to
      distinguish the simultaneous presence of different molecules in biological
      samples. MATERIAL AND METHOD: Amniochorion explants were obtained from women at
      term with spontaneous labor (n = 4) and subjected to cesarean section without
      labor (n = 4). Explants were cultured for 24 h and then homogenated in their own
      culture media to obtain cell free extracts. Chemokines were identified in these
      extracts using a commercial array for chemokines that included: eotaxin, eotaxin
      2, 1-309, IL-8, IP-10, MCP-1, MCP-2, MIG, MIP-1alpha, MIP-1beta, MIP-1delta and
      RANTES. RESULTS: All the included chemokines were found in amniochorion extracts,
      being IL-8 the most abundant. However, once labor is present, all chemokines tend
      to appear in greater concentrations than those from non-in-labor tissues, except
      for RANTES, which disappeared when labor began. CONCLUSION: This methodological
      approach shows that amniochorion from term pregnancies secrete chemokines with a
      characteristic qualitative profile during labor. This approach would allow the
      fast evaluation of potential markers of this phenomenon in physiologic or
      pathologic conditions.

PMID- 17539323
TI  - [Identification of extracellular matrix metalloprotease 3 in the fetal membrane
      of the rat and its possible implication in the rupture of chorioamniotic
      membranes].
AB  - OBJECTIVE: Human corioamniotic membranes, or their equivalent in the rat,
      function as selective barrier during gestation and their rupture is part of the
      mechanisms implied in the labor. Molecular mechanisms carried out in this process
      are unknown. TYPE OF STUDY: Experimental animal model. MATERIAL AND METHODS:
      Corioamniotic membranes (obtained at the beginning of the labor) of rats with
      programmed and synchronous pregnancies were analized. The coexistence and
      distribution of metalloproteinase of extracellular-3 matrix (estromelisine) in
      these tissues were determined. RESULTS: Secretion and tissue location of
      metalloproteinase of extracellular-3 matrix in fetal membranes were identified
      for the first time. Metalloproteinase of extracellular-3 matrix was immunolocated
      in the compact layer of the amnion and its secretion (by the membranes) was
      confirmed through electrophoresis, zimography and Western blot. By confocal
      microscopy it was verified that metalloproteinase of extracellular-3 matrix is
      located in the same places of that of extracellular-9 matrix. CONCLUSIONS:
      Rupture of corioamniotic membranes relates to the expression and local activity
      of the metalloproteinases of extracellular matrix. The coexistence of
      metalloproteinase of extracellular-3 matrix in the amnion of the rat has been
      identified; this element is added to the biochemical process of rupture, since
      metalloproteinase of extracelular-3 matrix is an activator of that of
      extracellular-9 matrix. It is possible that the physiological function of this
      enzyme is implied, of a main way, in the process of rupture of corioamniotic
      membranes during the childbirth.

PMID- 17539324
TI  - [Surgery in vaginal delivery. 1951].

PMID- 17539328
TI  - Health funding needs reform.

PMID- 17539329
TI  - Health at the crossroads. Who will lead the way?

PMID- 17539330
TI  - Sudan experience will help shape future practice.

PMID- 17539331
TI  - Family orientated delivery of routine nursing care in hospital.

PMID- 17539332
TI  - Eight essential factors for successful nurse-led services.

PMID- 17539333
TI  - Project to improve pregnancy outcomes.

PMID- 17539335
TI  - Nurses and community engagement.

PMID- 17539336
TI  - Nurses lead the way in prostate cancer care.

PMID- 17539337
TI  - Major change for nursing.

PMID- 17539338
TI  - Computerised cognitive behavioural therapy (CCBT) in Singapore--a nursing anti
      depression mental health promotion initiative.

PMID- 17539339
TI  - No substitute for family--but nurses a close second.

PMID- 17539340
TI  - [40th anniversary of the Central Research Institute of Gastroenterology].

PMID- 17539341
TI  - [Development of enterology in the Central Research Institute of
      Gastroenterology].

PMID- 17539342
TI  - [40th anniversary of the X-ray Department in the Central Research Institute of
      Gastroenterology].

PMID- 17539343
TI  - [Helicobacter pylori infection in studies conducted by the Central Research
      Institute of Gastroenterology].

PMID- 17539344
TI  - [Chronic viral hepatitis: achievements and prospects].

PMID- 17539345
TI  - [Intravital morphological examination of the liver].

PMID- 17539346
TI  - [Major achievements of biliary science for 40 years].
AB  - The review presents data on major achievements in the field of biliary pathology
      studies for the past 40 years. The article consists of several sections:
      choleresis and biliary excretion, pathogenesis, clinical picture, diagnostics and
      treatment. The article also discloses major achievements in biliary pathology
      studies of both foreign and native researchers including the contribution made by
      researchers from the Central Research Institute of Gastroenterology. In vitro
      study of the acid neutralizing effect of antiacid drugs.

PMID- 17539347
TI  - [Hepatolenticular degeneration: yesterday, today, tomorrow].

PMID- 17539348
TI  - [Barrett's esophagus and esophageal adenocarcinoma].

PMID- 17539349
TI  - [Chronic ischemic disease of the digestive system: clinical course variants,
      diagnostics, and treatment].

PMID- 17539350
TI  - [Ulcerative colitis: major components of diagnostics and treatment].

PMID- 17539351
TI  - [Experimental gastric and duodenal ulcer models: their potential and
      restrictions].

PMID- 17539352
TI  - [Diagnostic and prognostic value of humoral immune status indices for alimentary
      system diseases].
AB  - The paper describes the results of studying the immune status of 1,960 patients
      with stomach, pancreas, liver, gall bladder, small and large intestine disorders,
      who were treated in the Central Research Institute of Gastroenterology. The
      results of the study demonstrate that alimentary system diseases are concomitant
      with changes in the functional activity of the immune system and development of
      the systemic immune response aimed at the neutralization and elimination of
      pathogenic agents. Impaired regulatory and efferent lymphocyte capacities,
      increased synthesis of cytokines, immunoglobulins, heterologous (anti-viral, anti
      bacterial or antigliadin), autologous (to parietal cells, microsome mitochondria,
      tissue transglutaminase) antibodies, formation of immune complexes, autoimmune
      reactions and secondary immunodeficiency are specific immune mechanisms of the
      pathological process development, its synchronization and progression in patients
      with alimentary system diseases. Changes in the immunological status indices are
      expressed in varying degree depending on the organ involved, etiological factor,
      clinical course and stage of the disease, as well as treatment used. The
      immunological status indices have maximal values in cases of chronic hepatitis,
      hepatic cirrhosis, peptic or duodenal ulcer, cholelithiasis, chronic
      pancreatitis, gluten-sensitive enteropathy and minimal values in cases of chronic
      gastritis, gastroesophageal disease, steatohepatitis and irritable bowel
      syndrome. These data are sufficient for developing an algorithm of immune
      diagnostics for a number of alimentary system diseases. The study of immune
      status indices is of great diagnostic and prognostic value as it defines the
      etiological factor, intensity of inflammatory, infectious and autoimmune
      processes as well as disease stage and activity, its forecast and the efficacy of
      treatment of alimentary system diseases.

PMID- 17539353
TI  - [Thirteen months at Ege University: up-to-date medical technologies in ancient
      Izmir].

PMID- 17539354
TI  - [Modern strategy in the treatment of chronic hepatitis B: progress and
      prospects].

PMID- 17539355
TI  - [Algorithm for diagnostics of iatrogenic liver lesions and their management
      tactics].

PMID- 17539356
TI  - [Assessment of the efficacy of mebeverine in the complex therapy of chronic
      noncalculolis cholecystitis and biliary dysfunction].

PMID- 17539357
TI  - [Using neosmectin in the complex therapy of patients with acute intestinal
      infections].

PMID- 17539358
TI  - [Nutritive support using special mixtures for enteral nutrition in the intensive
      therapy of patients with peritonitis].

PMID- 17539359
TI  - [Role of Helicobacter and lamblia infections in the diagnostics and treatment of
      chronic hives].
AB  - Chronic recurrent urticaria is a pluricausal disease observed not only by
      allergologists but also by gastroenterologists and general practitioners in their
      practice. Two concomitant pathological processes--urticaria and chronic
      inflammatory diseases of the gastrointestinal tract, especially in cases of
      helminthic infections--are examined in full measure. This article also describes
      the concomitant effect of Helicobacter pylori and G. lamblia infections as the
      most frequent factor inducing the development of chronic urticaria. These
      particular features of its etiology served as the basis for introducing up-to
      date high-technology diagnostics methods and developing corresponding approaches
      to the treatment of patients suffering from this disease.

PMID- 17539360
TI  - Young Netherlands Twin Register (Y-NTR): a longitudinal multiple informant study
      of problem behavior.
AB  - The Netherlands Twin Register (NTR) was established around 1987 at the Vrije
      Universiteit in Amsterdam, the Netherlands. The current article summarizes the
      longitudinal genetic analyses of maternal and paternal ratings of twins' behavior
      as a function of the sex of the children for the traits of aggression (AGG),
      attention problems (AP), anxious/depression (ANX), internalizing behavior (INT)
      and externalizing behavior (EXT). We found that genetic influences are the most
      important factor in explaining individual differences in these traits. For most
      phenotypes, influences of genetic factors fluctuate throughout development, with
      the exception of AP, for which genetic influences remain of similar magnitude.
      Changes in genetic influences parallel those in shared environmental influences,
      while nonshared environmental influences remain relatively constant. Around 10%
      to 20% of the variance is accounted for by parent-specific shared environment,
      which includes rater bias. For all phenotypes, stability throughout childhood is
      accounted for by genetic and shared environmental factors, while nonshared
      environmental influences are mainly age/measurement specific. About 15% of the
      phenotypic stability is accounted for by rater-specific shared environmental
      influences, which include rater bias. In conclusion, between ages 3 and 12
      genetic factors are the most important cause of individual differences in
      emotional and behavioral problems.

PMID- 17539361
TI  - The Cardiff Study of all Wales and North West of England Twins (CaStANET): a
      longitudinal research program of child and adolescent development.
AB  - The study of twins and their families provides a highly useful tool for
      disentangling the genetic and environmental origins of traits. The Cardiff Study
      of All Wales and North West of England Twins (CaStANET) has followed children and
      adolescents over time into early adulthood, assessing a wide range of aspects of
      behavior and psychopathology using self-, parent and teacher reports. Four main
      waves of data collection have taken place to date, which have provided a wealth
      of information on the contributions of genetic and environmental risk factors to
      the psychological health of young people. This article first describes the
      CaStANET register and subsequently presents some of the findings that have
      emerged from this resource, with a focus on depression and anxiety, chronic
      fatigue, attention-deficit/hyperactivity disorder, conduct problems and prosocial
      behavior. We describe in somewhat more detail the 4th wave of data collection,
      which has recently been completed and has provided us with extensive information
      on substance use and problem use as well as associated risk factors in the twins
      and their families, including longitudinal data on conduct problems and the
      relations between family members. Because of the wealth of data already collected
      and the opportunity for genetically informative analyses over time, CaStANET
      provides a valuable resource for understanding the complexities of the
      psychological development of young people.

PMID- 17539362
TI  - Personality at ages 16 and 17 and drinking problems at ages 18 and 25: genetic
      analyses of data from Finn Twin16-25.
AB  - We enrolled more than 3500 same-sex twinsfrom 5 consecutive Finnish birth cohorts
      into a longitudinal study as each cohort reached age 16. Twins completed the
      Psychopathic Deviate (Pd) Scale of the Minnesota Multiphasic Personality
      Inventory at baseline, Sensation Seeking Scale items as each cohort reached age
      17, and later, at average ages 18.5 and 25, the Rutgers Alcohol Problem Index
      (RAPI). Using raw maximum likelihood estimation, we fit a Cholesky model to the 4
      variables assessed at 4 ages across the 4 twin types; we estimated genetic and
      environmental influences on the stability of alcohol problems across development
      and the genetic and environmental contributions to predictive correlations
      between adolescent personality and later alcohol-related behavior problems. With
      one exception, the phenotypic, genetic, and environmental correlations were very
      similar for males and females. The exception was that the lagged associations of
      Pd and RAPI reflect a higher genetic correlation among males than females and a
      higher environmental correlation among females than males. Our analyses suggest
      that developmental changes underlying variation in alcohol problems from late
      adolescence to early adulthood differ for males and females. In males, the main
      change is decreased variation due to shared environmental effects; the magnitude
      of genetic effects is stable over time, and the high genetic correlation, .95,
      suggests that the same genetic influences are important at both ages. Among
      females, in contrast, genetic influences decline in magnitude from age 18 to 25,
      and at least part of the genetic effect evident at age 25 differs from the
      genetic effect evident at age 18.

PMID- 17539363
TI  - Early childhood temperament and the covariation between internalizing and
      externalizing behavior in school-aged children.
AB  - There is significant covariation between internalizing and externalizing
      behavior, although there is also evidence that internalizing behavior is a
      protective factor against externalizing behavior. Several researchers have
      posited that the examination of the relationship between temperament or
      personality and behavior problems may help explain these seemingly contradictory
      results. Specifically, negative emotionality or neuroticism has been cited as a
      temperament characteristic that internalizing and externalizing behavior share in
      common, whereas behavioral inhibition may be related only to internalizing
      behavior. We examined the degree to which the covariation between internalizing
      and externalizing behavior assessed from age 4 to 12 years can be explained by
      temperament characteristics assessed from age 14 to 36 months. Additionally, we
      assessed the extent to which this relationship is due to genetic or environmental
      factors, analyzing data from 225 monozygotic and 185 dizygotic twin pairs
      assessed by the Colorado Longitudinal Twin Study. In males, a portion of the
      covariation between internalizing and externalizing behavior was explained by
      shared environmental influences in common with emotionality and shared
      environmental influences in common with shyness. In females, most of the
      covariation between internalizing and externalizing behavior was explained by
      shared environmental influences in common with emotionality. A possible
      limitation of this study is that the covariation between temperament and behavior
      problems may be due to shared measurement variance, as parent ratings were used
      to assess both temperament and behavior problems.

PMID- 17539364
TI  - Early onset problem behavior, young adult psychopathology, and contextual risk.
AB  - A prospective study of 692 male twins was undertaken to investigate the
      relationships among early adolescent problem behavior, contextual risk, and
      disinhibitory psychopathology. Early adolescent problem behavior was assessed by
      the number of the following behaviors engaged in by the time of the age-14
      assessment: (1) tobacco use, (2) alcohol use, (3) marijuana use, (4) other
      illicit drug use, (5) sexual intercourse, and (6) police contact. Contextual risk
      was assessed as a composite of measures of peer models, parent-offspring
      conflict, and academic engagement from the age-14 assessment. Disinhibitory
      psychopathology was assessed by symptoms of nicotine dependence, alcohol
      dependence, drug dependence, and adult antisocial behavior at the age-18
      assessment. Early adolescent problem behavior and contextual risk were strongly
      correlated (r = .53) and both were strongly and independently associated with
      symptoms of disinhibitory psychopathology (r from .35 to .60). The association of
      early adolescent problem behavior with both contextual risk and disinhibitory
      psychopathology was mediated entirely by genetic factors while the association
      between contextual risk and disinhibitory psychopathology was mediated by both
      genetic and nonshared environmental factors. The results are discussed in the
      context of emerging research on the prognostic significance of early adolescent
      problem behavior for risk of adult psychopathology.

PMID- 17539365
TI  - Longitudinal genetic analysis of internalizing and externalizing problem behavior
      in adopted biologically related and unrelated sibling pairs.
AB  - To obtain a better understanding of how genetic and environmental processes are
      involved in the stability and change in problem behavior from early adolescence
      into adulthood, studies with genetically informative samples are important. The
      present study used parent-reported data on internalizing and externalizing
      problem behavior of adoptees at mean ages 12.4, 15.5 and 26.3. In this adoption
      study adopted biologically related sibling pairs shared on average 50% of their
      genes and were brought up in the same family environment, whereas adopted
      biologically unrelated sibling pairs only shared their family environment. The
      resemblance between these adopted biologically related (N = 106) and unrelated
      sibling pairs (N=230) was compared and examined over time. We aimed to
      investigate (1) to what extent are internalizing and externalizing problem
      behavior stable from early adolescence into adulthood, and (2) whether the same
      or different genetic and environmental factors affect these problem behaviors at
      the 3 assessments. Our results show that both internalizing (rs ranging from .34
      to .58) and externalizing behavior (rs ranging from .47 to .69) were rather
      stable over time. For internalizing and externalizing problem behavior it was
      found that both genetic and shared environmental influences could be modeled by
      an underlying common factor, which explained variance in problem behavior from
      early adolescence into adulthood and accounted for stability over time. The
      nonshared environmental influences were best modeled by a Cholesky decomposition
      for internalizing behavior, whereas a time-specific influence of the nonshared
      environment was included in the final model of externalizing behavior.

PMID- 17539366
TI  - The Swedish Twin study of CHild and Adolescent Development: the TCHAD-study.
AB  - The Swedish Twin study of CHild and Adolescent Development (TCHAD) is a
      longitudinal study of how genes and environments contribute to development of
      health and behavioral problems from childhood to adulthood. The study includes
      1480 twin pairs followed since 1994, when the twins were 8 to 9 years old. The
      last data collection was in 2005 when the twins were 19 to 20 years old. Both
      parents and twins have provided data. In this article we describe the sample,
      data collections, and measures used. In addition, we provide some key findings
      from the study, focusing on antisocial behavior, criminality, and psychopathic
      personality.

PMID- 17539367
TI  - The Nonshared Environment in Adolescent Development (NEAD) project: a
      longitudinal family study of twins and siblings from adolescence to young
      adulthood.
AB  - The Nonshared Environment in Adolescent Development (NEAD) project is a
      longitudinal study of twins/siblings and parents that has been assessed 3 times:
      middle adolescence, late adolescence and young adulthood (N=720 families at Time
      1). Siblings varied in degree of genetic relatedness including identical twins,
      fraternal twins, full siblings, half siblings and genetically unrelated (or step)
      siblings. There were also two family types: nondivorced and step. A multimeasure,
      multirater approach was taken in NEAD, with data collected from all participants
      (2 twins or siblings, mother and father) as well as from coded videotaped
      observations of family interactions. Detailed assessments of family
      relationships, adolescent adjustment and competence were collected at all 3
      times. The original aim of NEAD was to identify systematic sources of nonshared
      environmental influences that contribute to differences among family members.
      Although systematic sources of nonshared environmental influences were not found
      in NEAD, three major sets of findings emerged: (1) genetic influences on family
      relationships and on associations between family relationships and adolescent
      adjustment; (2) genetic and environmental influences on adolescent adjustment,
      comorbidity and stability and change in adolescent adjustment from middle to late
      adolescence; and (3) genetic influences on relationships outside the family.

PMID- 17539368
TI  - The early growth and development study: a prospective adoption design.
AB  - The Early Growth and Development Study is a prospective adoption study of birth
      parents, adoptive parents, and adopted children (N=359 triads) that was initiated
      in 2003. The primary study aims are to examine how family processes mediate or
      moderate the expression of genetic influences in order to aid in the
      identification of specific family processes that could serve as malleable targets
      for intervention. Participants in the study are recruited through adoption
      agencies located throughout the United States, following the birth of a child.
      Assessments occur at 6-month intervals until the child reaches 3 years of age.
      Data collection includes the following primary constructs: infant and toddler
      temperament, social behavior, and health; birth and adoptive parent personality
      characteristics, psychopathology, competence, stress, and substance use; adoptive
      parenting and marital relations; and prenatal exposure to drugs and maternal
      stress. Preliminary analyses suggest the representativeness of the sample and
      minimal confounding effects of current trends in adoption practices, including
      openness and selective placement. Future plans are described.

PMID- 17539369
TI  - Twins' Early Development Study (TEDS): a multivariate, longitudinal genetic
      investigation of language, cognition and behavior problems from childhood through
      adolescence.
AB  - The Twins' Early Development Study (TEDS) is a large-scale longitudinal study of
      twins from early childhood through adolescence. Since its conception, TEDS has
      had as its focus the study of problematic development within the context of
      normal variation, mainly in the development of language, cognitive and academic
      abilities and behavior problems from multivariate quantitative and molecular
      genetic perspectives. TEDS twins have been assessed at 2, 3, 4, 7, 9, 10 and
      (currently) 12 years of age, and DNA collected from more than 12,000 children.
      Identified from birth records of twins born in the United Kingdom between 1994
      and 1996, more than 15,000 pairs of twins originally enrolled in TEDS, and well
      over 13,000 pairs--representative of the U.K. population--remain involved in the
      study to date. Similar to many other twin and adoption studies, TEDS data
      indicate that both genetic and environmental influences are important in nearly
      all areas of behavioral development. Multivariate genetic analyses allow
      researchers to go beyond this basic nature-nurture question, and TEDS results
      suggest that, especially in the area of learning abilities and disabilities,
      genes are generalists and environments are specialists. That is, genes largely
      contribute to similarity in performance within and between learning abilities and
      disabilities and across age, whereas the environment contributes to differences
      in performance. Quantitative genetic findings such as these chart the course for
      molecular genetic research. The TEDS dataset is proving valuable in genome-wide
      association research that tries to identify some of the many genes responsible
      for the ubiquitous heritability of behavior.

PMID- 17539370
TI  - Developmental origins of low mathematics performance and normal variation in
      twins from 7 to 9 years.
AB  - A previous publication reported the etiology of mathematics performance in 7-year
      old twins (Oliver et al., 2004). As part of the same longitudinal study we
      investigated low mathematics performance and normal variation in a representative
      United Kingdom sample of 1713 same-sex 9-year-old twins based on teacher-assessed
      National Curriculum standards. Univariate individual differences and DeFries
      Fulker extremes analyses were performed. Similar to our results at 7 years, all
      mathematics scores at 9 years showed high heritability (.62-.75) and low shared
      environmental estimates (.00-.11) for both the low performance group and the full
      sample. Longitudinal analyses were performed from 7 to 9 years. These
      longitudinal analyses indicated strong genetic continuity from 7 to 9 years for
      both low performance and mathematics in the normal range. We conclude that,
      despite the considerable differences in mathematics curricula from 7 to 9 years,
      the same genetic effects largely operate at the two ages.

PMID- 17539371
TI  - Longitudinal analyses of affect, temperament, and childhood psychopathology.
AB  - The Wisconsin Twin Panel utilizes the resources of state birth records to study
      the etiology and developmental course of early emotions, temperament, childhood
      anxiety and impulsivity, the autism spectrum, and related psychobiological and
      behavioral phenotypes. The panel currently supports 5 active research studies
      which involve twins from birth to early adolescence. A range of research methods
      are employed, including questionnaires and structured interviews with caregivers,
      home and laboratory-based behavioral batteries, observer ratings, child self
      report, psychophysiology, neuroendocrine measures, birth records, genotyping, and
      cognitive testing. The panel is in the early stages of generating longitudinal
      findings.

PMID- 17539372
TI  - A longitudinal genetic study of plasma lipids in adolescent twins.
AB  - Plasma lipids such as high-density lipoprotein (HDL), low-density lipoprotein
      (LDL), total cholesterol and triglyceride levels contribute to variation in the
      risk of cardiovascular disease. The early stages of atherosclerosis in childhood
      have also been associated with changes in triglycerides, LDL and HDL.
      Heritability estimates for lipids and lipoproteins for adolescents are in the
      range .71 to .82, but little is known about changes of genetic and environmental
      influences over time in adolescence. We have investigated the contribution of
      genetic and environmental influences to variation in lipids in adolescent twins
      and their nontwin siblings using longitudinal twin and family data. Plasma HDL
      and LDL cholesterol, total cholesterol and triglycerides data from 965 twin pairs
      at 12, 14 and 16 years of age and their siblings have been analyzed. Longitudinal
      genetic models that included effects of age, sex and their interaction were
      fitted to assess whether the same or different genes influence each trait at
      different ages. Results suggested that more than one genetic factor influences
      HDL, LDL, total cholesterol and triglycerides over time at ages 12, 14 and 16
      years. There was no evidence of shared environmental effects except for HDL and
      little evidence of long-term nonshared environmental effects was found. Our study
      suggested that there are developmental changes in the genes affecting plasma
      lipid concentrations across adolescence.

PMID- 17539373
TI  - Genetic and cultural transmission of antisocial behavior: an extended twin parent
      model.
AB  - Considerable evidence from twin and adoption studies indicates that both genetic
      and shared environmental factors play a substantial role in the liability to
      antisocial behavior. Although twin and adoption designs can resolve genetic and
      environmental influences, they do not provide information about assortative
      mating, parent-offspring transmission, or the contribution of these factors to
      trait variation. We examined the role of genetic and environmental factors for
      conduct disorder (CD) using a twin-parent design. This design allows the
      simultaneous estimation of additive genetic, shared and individual-specific
      environmental effects, as well as sex differences in the expression of genes and
      environment in the presence of assortative mating and combined genetic and
      cultural transmission. A retrospective measure of CD was obtained from twins and
      their parents or guardians in the Virginia Twin Study of Adolescent Behavior
      Development and its Young Adult Follow up sample. Both genetic and environmental
      factors play a significant role in the liability to CD. Major influences on
      individual differences appeared to be additive genetic (38%-40%) and unique
      environmental (39%-42%) effects, with smaller contributions from the shared
      environment (18%-23%), assortative mating (-2%), cultural transmission
      (approximately 2%) and resulting genotype-environment covariance. This study
      showed significant heritability, which is slightly increased by assortative
      mating, and significant effects of primarily nonparental shared environment on
      CD.

PMID- 17539374
TI  - Stability of genetic and environmental effects from adolescence to young
      adulthood: results of Croatian longitudinal twin study of personality.
AB  - The primary aim of this study was to conduct a bivariate genetic analysis
      investigating the extent to which genetic and environmental factors contribute to
      stability and change in personality factors in the period from adolescence to
      young adulthood on a sample of Croatian twins. The sample used in this research
      was formed in 1992 based on a register of citizens of Zagreb and data was
      collected for 160 twin pairs (75 monozygotic and 85 dizygotic twin pairs). Twins
      were tested twice, 4 years apart with the Eysenck Personality Questionnaire (mean
      age at first time point was 17 years). Univariate analyses indicate that the best
      fitting model for extraversion, neuroticism, psychoticism and lie scale at both
      time points includes additive genetic (A) and nonshared environmental (E)
      influences, with heritability estimates in the .40 to .50 range. Longitudinal
      analyses using AE correlated factors model indicate that genetic factors
      contribute mainly to stability, while environmental factors contribute mainly to
      change in personality during that 4-year period of transition from adolescence to
      young adulthood.

PMID- 17539375
TI  - Statistical power to detect genetic and environmental influences in the presence
      of data missing at random.
AB  - We study the situation in which a cheap measure (X) is observed in a large,
      representative twin sample, and a more expensive measure (Y) is observed in a
      selected subsample. The aim of this study is to investigate the optimal selection
      design in terms of the statistical power to detect genetic and environmental
      influences on the variance of Y and on the covariance of X and Y. Data were
      simulated for 4000 dizygotic and 2000 monozygotic twins. Missingness (87% vs.
      97%) was then introduced in accordance with 7 selection designs: (i) concordant
      low + individual high design; (ii) extreme concordant design; (iii) extreme
      concordant and discordant design (EDAC); (iv) extreme discordant design; (v)
      individual score selection design; (vi) selection of an optimal number of MZ and
      DZ twins; and (vii) missing completely at random. The statistical power to detect
      the influence of additive and dominant genetic and shared environmental effects
      on the variance of Y and on the covariance between X and Y was investigated. The
      best selection design is the individual score selection design. The power to
      detect additive genetic effects is high irrespective of the percentage of
      missingness or selection design. The power to detect shared environmental effects
      is acceptable when the percentage of missingness is 87%, but is low when the
      percentage of missingness is 97%, except for the individual score selection
      design, in which the power remains acceptable. The power to detect D is low,
      irrespective of selection design or percentage of missingness. The individual
      score selection design is therefore the best design for detecting genetic and
      environmental influences on the variance of Y and on the covariance of X and Y.
      However, the EDAC design may be preferred when an additional purpose of a study
      is to detect quantitative trait loci effects.

PMID- 17539376
TI  - A more accurate estimate of heritability.
AB  - All psychological and psychophysiological traits vary, often widely, about their
      stable set-point values, due to transitory environmental influences. Because it
      is this stable set-point that embodies the genetically determined component of
      the trait, twin and family data based on one-time trait measurements must
      underestimate true trait heritability. The means of multiple measurements, taken
      months or years apart, then correlated within pairs of monozygotic twins, would
      yield an accurate estimate of the broad heritability of the set-point value, but
      such data are rare and expensive. Given just two measurements sufficiently far
      apart, the cross-twin cross-time correlation (R(CT)), divided by the retest or
      within-twin cross-time correlation (R(WT)), provides a valid estimate of set
      point heritability. This article examines data from young and middle-aged twins
      who were tested twice, 3 or more years apart, on heart rate and blood pressure,
      personality traits, self-rating items, occupational and recreational interests,
      as well as on Wechsler Intelligence Scales. In every case, the disattenuated
      R(CT) revealed substantially higher heritability than indicated by correlations
      based on single measurements.

PMID- 17539377
TI  - Genetic and environmental contributions to pathological gambling symptoms in a 10
      year follow-up.
AB  - Problem (P) and pathological gambling (PG) symptoms wax and wane. Past symptoms
      are a risk for future symptoms even after controlling for familial influences. To
      address the genetic architecture of lifetime PG and current PG symptoms, we
      tested for common and unique genetic factors to lifetime PG symptoms at baseline
      and past year PG symptoms at 10-year follow-up. Diagnostic and Statistical Manual
      of Mental Disorders (3rd ed., Rev.; DSM-III-R; American Psychiatric Association,
      1987) lifetime criteria of one or more PG symptoms were derived in 1992 and past
      year PG symptoms in 2002 from 1675 individual twins from the Vietnam Era Twin
      Registry. Cholesky decomposition models were fit to baseline and past year PG
      symptoms. Under the best fitting model we observed that 49% of the risk for one
      or more baseline PG symptoms in 1992 was due to a genetic factor and 51% of the
      risk was due to a unique environmental factor. All of the genetic variance
      (57.5%) in risk to past year PG symptoms in 2002 was common with baseline PG
      symptoms. Unique environment accounted for the remaining variance in past year PG
      symptoms with 13% common to baseline and 30% specific to past year PG symptoms.
      The genetic contributions to lifetime and past year gambling symptoms 10 years
      later are similar. There is no evidence for genetic contributions unique to past
      year PG symptoms. However, most of the unique environmental influences to past
      year PG are not shared with lifetime PG. This may reflect the changed social
      cultural environment between 1992 and 2002, characterized by increasing access to
      legalized gambling.

PMID- 17539378
TI  - Covariance of isometric and dynamic arm contractions: multivariate genetic
      analysis.
AB  - The purpose of the present study was to examine genetic and environmental
      contributions to individual differences in maximal isometric, concentric and
      eccentric muscle strength and muscle cross-sectional area (MCSA) of the elbow
      flexors. A generality versus specificity hypothesis was explored to test whether
      the 4 strength variables share a genetic component or common factors in the
      environment or whether the genetic/environmental factors are specific for each
      strength variable. The 4 variables under study were measured in 25 monozygotic
      and 16 dizygotic male Caucasian twin pairs (22.4 +/- 3.7 years). The multivariate
      genetic analyses showed that all 4 variables shared a genetic and environmental
      component, which accounted for 43% and 6% in MCSA (h2 = 81%), 47% and 20% in
      eccentric (h2 = 65%), 58% and 4% in isometric (h2 = 70%) and 32% and 1% in
      concentric strength (h2 = 32%) respectively. The remaining variation was
      accounted for by contraction type specific and muscle cross-sectional area
      specific genetic and environmental effects, which accounted for 38% and 14% in
      MCSA, 18% and 15% in eccentric, 12% and 26% in isometric and 0% and 67% in
      concentric strength respectively. This exploratory multivariate study suggests
      shared pleiotropic gene action for MCSA, eccentric, isometric and concentric
      strength, with a moderate to high genetic contribution to the variability of
      these characteristics.

PMID- 17539379
TI  - The role of gene-environment interaction in determining bone mineral density in a
      twin population.

PMID- 17539380
TI  - Prenatal sonographic prediction of twin growth discordance.

PMID- 17539381
TI  - Vanishing twin: a possible cause of cerebral impairment.
AB  - Fetal death in a twin conception during second and third trimester is associated
      with increased risk of cerebral injury in the surviving twin. The aim of this
      study is to test the hypothesis that even early fetal losses as a 'vanishing'
      twin may be associated with an increased risk of cerebral impairment in the
      surviving twin. The study population comprised 362 pregnant women attending
      Liverpool Women's Hospital recruited between 1999 and 2001. Women were classified
      according to the first ultrasound scan into 3 groups: vanishing twin, twin and
      singleton. The vanishing twin group was further subdivided into 'definite' and
      'probable'. Children from these pregnancies were assessed at 1 year of age for
      their development and neurological function using the Griffiths Mental and
      Developmental Scales and Optimality score. Children from 229 pregnancies (63.2%)
      attended the assessment. Information on children from a further 21 (5.8%)
      pregnancies was obtained through a review of hospital records. Cerebral
      impairment was found in 2 children from the vanishing twin group, 2 from the twin
      group and none from the singleton group. When cases with definite vanishing twin
      are considered there is a significant difference between the vanishing twin and
      singleton group (relative risk 6.1; 95% confidence interval 1.5-8.3; p = .03). An
      additional study with an increased sample size would enable a more robust
      conclusion.

PMID- 17539382
TI  - Comparative development of surviving co-twins of vanishing twin conceptions,
      twins and singletons.
AB  - Early loss of one fetus in a multiple gestation as a 'vanishing' twin is a well
      recognized phenomenon. It is uncertain whether this has an impact on the
      development of the surviving co-twin. The aim of this study is to compare the
      development of singletons, twins and the surviving co-twins of a vanishing twin.
      The 324 children born to 229 women who were recruited into the study between 1999
      and 2001 formed the study population. Children were assessed at 1 year of age
      with Griffiths Mental and Developmental Scales. A neurological examination was
      performed using an optimality score to exclude those with severe neurodisability.
      Three hundred and five children (92 singletons, 180 twins and 33 survivors with a
      vanishing twin) were included. The sub- and general quotient scores in singletons
      and surviving co-twins of a vanishing twin did not differ significantly. Twins
      had significantly lower scores than singletons in all areas of development and
      were more likely to be born early with lower birthweights. Following adjustment
      for gestation and birthweight, the difference between the two groups was
      nullified suggesting that the slower development of twins is related to their
      prematurity and lower birthweight.

PMID- 17539383
TI  - Ultrasound to identify cord knotting in monoamniotic monochorionic twins.
AB  - This case report demonstrates the use of ultrasound and doppler flow in the
      management of mono-amniotic monochorionic (M/M) twins. M/M twinning is a rare but
      significant event. It is associated with high rates of fetal mortality, most
      commonly cited at anywhere from between 30% and 70%. A common cause of death is
      cord entanglement. The case presented is that of a 19-year-old gravida 1 at 30
      weeks with M/M twins in which multiple cord knots were found by ultrasound color
      doppler flow after variable fetal heart rate decelerations occurred. This
      prompted a decision for immediate cesarean delivery with normal fetal outcomes.
      Improvements in perinatal imaging systems are therefore beneficial in the
      management of M/M twins.

PMID- 17539384
TI  - Pattern of twin placentation in Ghana.

PMID- 17539385
TI  - Community foundations set for pilots, but names under wraps.

PMID- 17539386
TI  - Family planning. Cash-strapped contraceptive services plead for a target.

PMID- 17539387
TI  - The great PBC debate.

PMID- 17539388
TI  - Just the end of the beginning for Monitor. Interview by Neil Goodwin.

PMID- 17539389
TI  - Barometer. Mental health April 2007.

PMID- 17539390
TI  - Northern Ireland. A different kind of revolution.
AB  - Northern Ireland's public sector has been slimmed down in line with similar moves
      around the UK. A study into future spending needs for health and social care
      found performance measurement lacking. Elements of the English NHS reforms are
      being taken on board--but still require the vote of the Assembly.

PMID- 17539391
TI  - Public health. Sex on the brain.

PMID- 17539392
TI  - Commissioning. Training for the times.

PMID- 17539394
TI  - A hidden heritage.

PMID- 17539395
TI  - Beating the bug.

PMID- 17539396
TI  - Tipped for the top.

PMID- 17539397
TI  - Springboard to success.

PMID- 17539398
TI  - Ten steps to carrying out a SWOT analysis.

PMID- 17539399
TI  - Clinical data standards and nursing.

PMID- 17539400
TI  - Comparing roles: senior nurses and modern matrons.

PMID- 17539401
TI  - Have your say.

PMID- 17539402
TI  - Parasite-induced alteration of diurnal rhythms in a freshwater snail.
AB  - The trematode Microphallus sp. alters the behavior of its snail intermediate
      host, Potamopyrgus antipodarum, in ways that seem to increase transmission to its
      final host, e.g., waterfowl, and decrease the probability of being eaten by other
      predators, e.g., fish. The parasite seems to cause the snail to move from the top
      to the bottom of rocks at about 0900 hr. Waterfowl feed predominantly before 0900
      hr, and fish feed predominantly after 0900 hr. In the present study, we tested
      the hypothesis that Microphallus sp.-infected snails exhibit a change in behavior
      at around 0900 hr by examining their response to light and vertical orientation
      before and after 0900 hr. Results demonstrated that uninfected snails generally
      move toward light, oriented downward, and move a greater distance in the light
      compared with the dark at all times of day. Microphallus sp.-infected snails
      behaved differently from uninfected snails in the early morning but similarly to
      uninfected snails in the late morning with regard to downward orientation and
      distance moved in response to light. Snails infected with parasites other than
      Microphallus sp. behaved similarly to uninfected snails during both time periods.
      These results suggest that Microphallus sp. manipulates the behavior of
      Potamopyrgus sp. by altering rates of movement in response to light and vertical
      orientation in a manner consistent with the hypothesized 0900-hr shift.

PMID- 17539403
TI  - Early stages of development of the Taenia solium metacestode in pigs.
AB  - In order to identify the early stages of Taenia solium metacestodes, 12 pigs were
      each fed 100,000 viable eggs and later killed and necropsied at different times
      after infection. Hematoxylin-eosin (HE) and immunohistochemical techniques (IHCs)
      were used to identify onchospheres and cysticerci in different tissues. At 2 days
      postinfection (dpi) structures compatible with onchospheres were found in the
      lumen of the small intestine, and in the mesenteric blood vessels and lymph
      nodes. At 4 dpi, these same structures were observed in the small intestine, the
      liver, and skeletal muscles. Between 6 and 39 dpi, they were found only in
      skeletal muscles. Between 2 and 6 dpi the postonchospheres were circular and oval
      shaped and measured between 6 and 34 x 27 microm. From 14 to 39 dpi, well
      developed metacestodes 550 x 750 microm were observed. IHCs support the
      identification of early stages of T. solium.

PMID- 17539404
TI  - The crowding effect and morphometric variability in Echinostoma caproni (Digenea:
      Echinostomatidae) from ICR mice.
AB  - Population density, or crowding, was examined to determine its effect on the
      morphometric variability of Echinostoma caproni (Digenea) in ICR mice. Six mice
      were infected with 25 and 100 metacercariae, and a single mouse was infected with
      300 metacercariae. All mice were infected at necropsy 22 days postinfection with
      recoveries of 77%, 69%, and 7.3%, respectively. Whole mounts were prepared, and
      31 characters were evaluated (25 direct measurements and 6 ratios). Univariate
      and multivariate statistical analysis revealed significant differences between
      adult worms from all 3 groups. Twenty-seven of 31 characters showed significant
      within-group differences, with the primary differences between worms from 25/100
      versus 300 metacercariae infections. Discriminant function analysis yielded a
      100% correct classification based on infection size, which is consistent with
      studies on distinct species of Echinostoma. The low recovery from the mouse
      infected with 300 metacercariae suggests inflammatory expulsion of juvenile worms
      and the possibility of immunity as a factor in the crowding effect. These results
      suggest that external factors may affect morphometric variability of digenetic
      trematodes to a larger degree than previously recognized.

PMID- 17539405
TI  - Haemodipsus brachylagi n. sp. (Phthiraptera: Anoplura: Polyplacidae), a new
      sucking louse from the pygmy rabbit in Nevada.
AB  - The male and female of Haemodipsis brachylagi n. sp. (Phthiraptera: Anoplura) are
      described from specimens collected from a pygmy rabbit, Brachylagus idahoensis
      (Merriam) (Lagomorpha: Leporidae), from Nevada. Morphological features that
      differentiate the new species from other known species of Haemodipsus are
      elucidated, and an identification key to both sexes of the 3 species now known
      from this genus in North America is included. Geographical distributions of the
      other 4 species of Haemodipsus known from other parts of the world are
      highlighted.

PMID- 17539406
TI  - Dispersal of Udonella australis (Monogenea: Udonellidae) between caligid copepods
      Caligus rogercresseyi and Lepeophtheirus mugiloidis on Chilean rock cod.
AB  - Udonella australis is a platyhelminth that lives on the surface of the
      ectoparasite copepods Caligus rogercresseyi and Lepeophtheirus mugiloidis, which
      coexist on the Chilean rock cod Eleginops maclovinus. The absence of a planktonic
      oncomiracidium stage in the life cycle of udonellids may limit their dispersal
      ability. However, the high prevalence and intensity of U. australis on C.
      rogercresseyi suggest they have developed dispersal strategies to compensate for
      the lack of a free-living larval stage. The goals of this study were to determine
      the main dispersal mechanisms of U. australis in 1 copepod species and to compare
      the dispersal ability of U. australis between 2 different copepod species.
      Chilean rock cods were infected with female (without udonellids) and male (with
      and without udonellids) C. rogercresseyi. Other fishes were also infected with
      this copepod (with U. australis) and with L. mugiloidis (without U. australis).
      The dispersal of udonellids among copepods occurs through both intraspecific and
      interspecific processes. The main dispersal mechanism appears to be copepod
      mating; contact between same-sex individuals is less important. Intraspecific
      dispersal seems to be more dependent on the number of udonellids per fish than on
      copepod abundance, as observed for interspecific dispersal.

PMID- 17539407
TI  - Activity periods and questing behavior of the seabird tick Ixodes uriae (Acari:
      Ixodidae) on Gull Island, Newfoundland: the role of puffin chicks.
AB  - Questing behavior of Ixodes uriae and their associated seasonal, host-feeding
      patterns are crucial to our understanding of tick life history strategies and the
      ecology of diseases that they transmit. Consequently, we quantified questing
      behavior of nymphs and adult female I. uriae ticks at Gull Island, a seabird
      colony in Newfoundland, Canada, to examine seasonal variation of off-host and on
      host tick activity. We sampled a total of 133 adult Atlantic puffins (Fratercula
      arctica), 152 puffin chicks, and 145 herring gull (Larus argentatus) chicks for
      ticks during the breeding seasons of 2004 and 2005. Questing ticks were sampled
      by dragging a white flannel cloth across the grassy breeding areas during the mo
      of May, June, July, and August. Nymph questing activity reached a peak during mid
      July (79 and 110 individuals/hr in 2004 and 2005, respectively). The prevalence
      of nymphs and adult female ticks on different seabird hosts varied between years
      and during the seasons. Puffin chicks had the highest prevalence (above 70% in
      July) of nymphs in both years and this was correlated with questing activity.
      Female ticks rarely fed on puffin chicks, but were prevalent on adult puffins and
      gulls, although prevalence and questing of ticks were not correlated in these
      hosts. These patterns of off-host and on-host tick activity suggests that I.
      uriae ticks likely use a combination of questing and passive waiting, e.g., in
      puffin burrows, to detect hosts, depending on the tick stage and the host
      species.

PMID- 17539408
TI  - Associations between shorebird abundance and parasites in the sand crab, Emerita
      analoga, along the California coast.
AB  - I investigated spatial variation in the prevalence and abundance of 4 species of
      parasites in the sand crab, Emerita analoga, on 8 sandy beaches along 800 km of
      the California coast, to assess the importance of bird abundance for the
      distribution of parasites among sand crab populations. I collected sand crabs and
      counted shorebirds and gulls at each beach during June and November 1994. Sand
      crabs served as intermediate hosts for 4 species of parasites, including a
      trematode, Spelotrema nicolli (Cable and Hunnienen, 1938); an acanthocephalan,
      Polymorphus kenti (Van Cleave, 1947); a nematode, Proleptus sp., and an
      unidentified trypanorhynch tapeworm. Among sand crab populations, there was
      substantial spatial variation in the prevalence and abundance of each parasite
      species. No latitudinal pattern was apparent for any of the 4 species observed.
      Temporally, parasite prevalence and abundance was significantly different between
      dates for all 4 parasites. Specifically, sand crab populations experienced higher
      trematode, nematode, and trypanorhynch prevalence and abundance in November than
      in June. In contrast, prevalence and abundance of acanthocephalans were higher in
      June than in November. There were strong positive associations between bird
      abundance and prevalence of parasitic infection for trematodes and
      acanthocephalans for some dates but not for nematodes or trypanorhynchs, which
      use elasmobranchs as definitive hosts. The spatial variation in prevalence and
      abundance of trematodes and acanthocephalans observed among sand crab populations
      may be attributed to the distribution and abundance of shorebirds and gulls that
      serve as definitive hosts.

PMID- 17539409
TI  - Pterygodermatites (Paucipectines) jagerskioldi (Nematoda: Rictulariidae) from
      Gracilinanus agilis and G. microtarsus (Marsupialia: Didelphidae) in Brazilian
      pantanal and Atlantic forest by light and scanning electron microscopy.
AB  - Pterygodermatites (Paucipectines) jagerskioldi Lent and Freitas, 1935, a
      parasitic nematode of the small intestine of the marsupial Gracilinanus agilis
      (Mammalia: Didelphidae) from the Pantanal of Mato Grosso do Sul state, and G.
      microtarsus from Atlantic Forest of Rio de Janeiro state, Brazil, were analyzed
      by light and scanning electron microscopy. Details of the surface topography such
      as the oral aperture, cephalic papillae, 2 papillae in posterior end, and
      longitudinal cuticular elements represented by combs and spines are presented
      along with measurements, adding new taxonomic characters to the previous
      diagnostic feature of P. (P.) jagerskioldi based on light microscopy. In
      addition, two new hosts records and two new geographical distributions for this
      nematode are reported.

PMID- 17539410
TI  - Experimental test for premunition in a lizard malaria parasite (Plasmodium
      mexicanum).
AB  - Premunition in Plasmodium spp. is the prevention of superinfection by novel
      genotypes entering an already established infection in a vertebrate host.
      Evidence for premunition was sought for the lizard malaria parasite, P.
      mexicanum, in its natural host, the fence lizard, Sceloporus occidentalis. Clonal
      diversity (= alleles for the haploid parasite) was determined with the use of 3
      microsatellite markers. Both naturally infected lizards (N = 25) and previously
      noninfected lizards (N = 78) were inoculated intraperitoneally (IP) with blood
      from donor infections and followed over a 3-mo period. Compared to the success of
      clonal establishment in all the naive lizards (78/78 successful), clones entering
      preexisting infections had a significant disadvantage (9/25 successful). The
      number of preexisting clones (1-2 vs. 3-4) within recipient infections had no
      effect on the success of superinfection. Infections that excluded entering novel
      clones did not have higher initial asexual parasitemia, but had a higher initial
      density of gametocytes, suggesting they were older. Infections allowing
      superinfection experienced a higher final parasitemia.

PMID- 17539411
TI  - Life cycle of Hepatozoon canis (Apicomplexa: Adeleorina: Hepatozoidae) in the
      tick Rhipicephalus sanguineus and domestic dog (Canis familiaris).
AB  - The life cycle of the apicomplexan protozoon Hepatozoon canis in its natural
      hosts Rhipicephalus sanguineus (tick) and Canis familiaris (domestic dog) was
      studied in an experimental infection. Tick nymphs were fed on a naturally
      infected dog, or they were infected by percutaneous injection of blood. Dogs were
      inoculated by ingestion of adult ticks containing mature oocysts. Gamonts were in
      syzygy 24 hr after percutaneous injection of ticks. Early oocysts were detected
      96 hr after nymph repletion, and mature oocysts in adult ticks were infective to
      dogs 40 days postmolt. Merogony was detected in dog bone marrow from 13 days
      postinoculation (PI) and included meronts containing 20-30 micromerozoites, and a
      second type with 2-4 macromerozoites. Monozoic cysts were observed in the spleen
      in conjunction with merogony. Gamontogony with infection of leukocytes by
      micromerozoites occurred from 26 days PI, and gamont parasitemia, which completed
      the life cycle, was detected 28 days PI. The length of the life cycle from
      nymphal attachment to parasitemia in dogs was 81 days. Increased body
      temperatures were evident from 16 to 27 days PI and paralleled the time of
      intensive bone marrow merogony. Skeletal pain and recumbency were manifested in 2
      dogs. This study further elucidates the life cycle of H. canis and provides a
      sequential morphologic description of H. canis merogony, gamontogony, and
      sporogony.

PMID- 17539412
TI  - Small frogs get their worms first: the role of nonodonate arthropods in the
      recruitment of Haematoloechus coloradensis and Haematoloechus complexus in newly
      metamorphosed northern leopard frogs, Rana pipiens, and woodhouse's toads, Bufo
      woodhousii.
AB  - Studies on the life cycles and epizootiology of North American frog lung flukes
      indicate that most species utilize odonates as second intermediate hosts; adult
      frogs become infected by ingesting odonate intermediate hosts. Newly
      metamorphosed frogs are rarely infected with these parasites, predominantly
      because they are gape-limited predators that cannot feed on large intermediate
      hosts such as dragonflies. We examined the role of the frog diet and potential
      intermediate hosts in the recruitment of the frog lung fluke, Haematoloechus
      coloradensis, to metamorphosed northern leopard frogs (Rana pipiens), Woodhouse's
      toads (Bufo woodhousii), and bullfrogs (Rana catesbeiana) from western Nebraska.
      Because of the uncertain validity of H. coloradensis as a distinct species from
      Haematoloechus complexus, morphological characters of both species were
      reevaluated and the life cycles of both species were completed in the laboratory.
      The morphological data on H. coloradensis and H. coimplexus indicate that they
      differ in their oral sucker to pharynx ratio, uterine loop distribution, and
      placement of vitelline follicles. However, in terms of their life cycles, both
      species are quite similar in their use of physid snails as first intermediate
      hosts, a wide range of nonodonate and odonate arthropods as second intermediate
      hosts, and leopard frogs and toads as definitive hosts. These results indicate
      that H. coloradensis and H. complexus are generalists at the second intermediate
      host level and might be able to infect newly metamorphosed leopard frogs and
      toads by using small nonodonate arthropods more commonly than other frog lung
      fluke species. Comparisons of population structure of adult flukes in newly
      metamorphosed leopard frogs indicate that the generalist nature of H.
      coloradensis metacercariae enables it to colonize young of the year leopard frogs
      more commonly than other Haematoloechus spp. that only use odonates as second
      intermediate hosts. In this respect, the generalist nature of H. coloradensis and
      H. complexus at the second intermediate host level is an avenue for the
      colonization of young of year frogs.

PMID- 17539413
TI  - Parasites of juvenile brook trout (Salvelinus fontinalis) from Hunt Creek,
      Michigan.
AB  - Four parasite species (Crepidostomum cooperi, Cystidicoloides ephemeridarum,
      Acanthocephalus dirus, Salmincola edwardsii) infected 215 juvenile brook trout
      (105 young-of-year; 110, 1-yr-old) from Hunt Creek, Michigan, in 2003, 2004, and
      2005. Prevalences of these species in 2004 (main study year) varied from 29 to
      37%. Crepidostomnum cooperi had the highest mean intensity and mean abundance,
      followed by C. ephemeridarum. The number of fish infected with each parasite
      species was significantly higher in 1-yr-old fish than in young-of-year fish.
      Also, the mean intensities and mean abundances of C. cooperi and C. ephemeridarum
      and the mean abundance of A. dirus were significantly higher in older fish. The
      mean intensity of C. cooperi and prevalence of A. dirus were significantly higher
      in fish between creek sections. Fish length had a significant positive effect on
      the abundances of C. cooperi and C. ephemeridarum; parasite species richness, on
      the abundances of A. dirus and S. edwardsii; and parasite species richness in the
      2003 and 2004 trout cohorts, respectively. Crepidostomum cooperi, C.
      ephemeridarum, A. dirus, and S. edwardsii commonly infect Michigan brook trout.
      The small number of parasite species infecting Hunt Creek brook trout is similar
      to the number of parasite species of brook trout from other Michigan creeks.

PMID- 17539414
TI  - Clarification of Cercaria sevillana (Digenea: Microphallidae) life cycle using
      morphological and molecular data.
AB  - Cercaria sevillana is the cercaria larval stage that infects the gonads and the
      digestive gland of its first intermediate host, Nassarius reticulatus. In this
      study the decapodous crustacean Carcinus maenas was used to determine if it would
      serve as second intermediate host in the parasite's life cycle. The latter
      hypothesis was based on the knowledge that C. maenas is the second intermediate
      host of several other digenean species. After dissection, it was possible to
      observe encysted metacercariae in the antennal glands of the green crab. After
      biochemical excystment, the metacercariae were processed for light and scanning
      electron microscopy. The morphological features observed led us to conclude that
      this species was a microphallid fluke, and it was identified as Gynaecotyla
      longiintestinata. To establish a possible relationship between C. sevillana and
      this metacercariae, the ITS1 region was analyzed. Thus, DNA was extracted from C.
      sevillana and from the cysts isolated from the antennal glands. The ITS1 region
      was amplified and sequenced, and the alignment clearly demonstrated that the
      cercaria and the metacercariae belonged to the same species, G. longiintestinata.

PMID- 17539415
TI  - Echinostomatid larval stages in Lymnaea viatrix (Gastropoda: Pulmonata) from
      southwest Patagonia, Argentina.
AB  - The partial life cycle of an echinostomatid found in Lymnaea viatrix from
      Patagonia, Argentina, was experimentally clarified. Emerging cercariae were
      exposed to laboratory-reared specimens of Biomphalaria sp. Metacercariae obtained
      from both naturally and experimentally infected snails were force-fed to chicks.
      Specimens recovered from the chicks belong to Echinoparyphium sp. on the basis of
      morphological features. The studied species possesses 43 collar spines arranged
      in 4-4-27-4-4 at all stages, a cercariae with over 100 small corpuscles in the
      excretory system, a cercariae tail without finfolds, and a metacercariae with a
      thin cyst wall. The present species cannot be assigned to Echinoparyphium
      megacirrus despite their morphological similarity because of differences in the
      habitats of L. viatrix and the intermediate hosts of E. megacirrus, namely
      Chilina dombeiana, Diplodon chilensis, and Temnocephala chilensis. More
      information on some life cycle stages and on the ecology of the intermediate
      hosts is needed to clarify the taxonomic status of the parasite. This study
      represents the first detailed description of parasites other than Fasciola
      hepatica in L. viatrix from Argentina.

PMID- 17539416
TI  - Expression of flotillin-1 on Eimeria tenella sporozoites and its role in host
      cell invasion.
AB  - Lipid rafts are detergent-resistant, liquid-ordered microdomains in plasma
      membranes that are enriched in cholesterol and sphingolipids and involved in
      intracellular signal transduction, membrane trafficking, and molecular sorting.
      In this study, we investigated the possibility that lipid rafts on Eimeria
      tenella sporozoites may act as platforms for host cell invasion. Flotillin-1, a
      resident protein of lipid rafts, was identified on E. tenella sporozoites and was
      prominently expressed at the apex of the cells, a region mediating host cell
      invasion. Pretreatment of sporozoites with antibody against flotillin-1 blocked
      parasite invasion. Furthermore, the anticoccidial drug, monensin, disrupted the
      localization of flotillin-1 within raft structures resulting in loss of invasion.
      We conclude that Eimeria sporozoites utilize lipid rafts containing flotillin-1
      for internalization into host cells.

PMID- 17539417
TI  - Serine protease activity in developmental stages of Eimeria tenella.
AB  - A number of complex processes are involved in Eimeria spp. survival, including
      control of sporulation, intracellular invasion, evasion of host immune responses,
      successful reproduction, and nutrition. Proteases have been implicated in many of
      these processes, but the occurrence and functions of serine proteases have not
      been characterized. Bioinformatic analysis suggests that the Eimeria tenella
      genome contains several serine proteases that lack homology to trypsin. Using RT
      PCR, a gene encoding a subtilisin-like and a rhomboid protease-like serine
      protease was shown to be developmentally regulated, both being poorly expressed
      in sporozoites (SZ) and merozoites (MZ). Casein substrate gel electrophoresis of
      oocyst extracts during sporulation demonstrated bands of proteolytic activity
      with relative molecular weights (Mr) of 18, 25, and 45 kDa that were eliminated
      by coincubation with serine protease inhibitors. A protease with Mr of 25 kDa was
      purified from extracts of unsporulated oocysts by a combination of affinity and
      anion exchange chromatography. Extracts of SZ contained only a single band of
      inhibitor-sensitive proteolytic activity at 25 kDa, while the pattern of
      proteases from extracts of MZ was similar to that of oocysts except for the
      occurrence of a 90 kDa protease, resistant to protease inhibitors. Excretory
      secretory products (ESP) from MZ contained AEBSF (4-[2-Aminoethyl]
      benzenesulphonyl fluoride)-sensitive protease activity with a specific activity
      about 10 times greater than that observed in MZ extracts. No protease activity
      was observed in the ESP from SZ. Pretreatment of SZ with AEBSF significantly
      reduced SZ invasion and the release of the microneme protein, MIC2. The current
      results suggest that serine proteases are present in all the developmental stages
      examined.

PMID- 17539418
TI  - Frequency and severity of musculoskeletal symptoms in humans during an outbreak
      of trichinellosis caused by Trichinella britovi.
AB  - Musculoskeletal symptoms such as myalgia are well-known features in the course of
      trichinellosis; however, the characteristics of musculoskeletal findings have
      been described in detail in only 1 study. The present study was aimed to
      determine the joint and muscle symptoms in subjects diagnosed with acute
      trichinellosis at our rheumatology unit during a Trichinella britovi outbreak
      that occurred in Izmir, Turkey, in 2004. In total, 98 patients (55 females, 43
      males; mean age 32.3 +/- 10.9 yr) were included in the study. A detailed history
      and full musculoskeletal examination were obtained in each patient. A self
      administered questionnaire developed for recording the musculoskeletal symptoms
      was completed monthly until all the symptoms were resolved. Pain at the joints,
      restriction of movements (in shoulders, elbows, wrists, knees, ankles, and
      temporomandibular joints), myalgia, and muscle weakness (neck and shoulder
      girdle, muscles of the upper and forearm, back, thigh, and calf muscles) were
      assessed in every patient. Eosinophil counts, serum levels of creatine kinase,
      and lactate dehydrogenase also were analyzed. The most frequent musculoskeletal
      symptoms were muscle pain (86 cases [87.8%]), joint pain (83 [84.7%]), subjective
      muscle weakness (75 [76.5%]), and restriction of joint movements (63 [64.3%]).
      Calves, upper arm, neck and shoulder girdle, and forearms were the most affected
      muscle groups. Muscle pain was reported more frequently in the upper than in the
      lower extremities and during activity. The most frequent painful joints were
      shoulders, knees, wrists, and ankles. Upper extremity joints were affected more
      frequently than the lower extremity joints (77.6 vs. 70.4%). Joint pain occurred
      more frequently at rest. Both muscle weakness and restriction of joint movements
      were reported in and around the most frequently affected regions. No evidence of
      arthritis and objective muscle weakness was noted on physical examination in any
      patient. Musculoskeletal symptoms in the course of T. britovi infection are
      frequent but with an excellent prognosis. Joint pain in people suffering from
      acute trichinellosis may occur more frequently than reported previously.

PMID- 17539419
TI  - Cystoisospora canis Nemeseri, 1959 (syn. Isospora canis), infections in dogs:
      clinical signs, pathogenesis, and reproducible clinical disease in beagle dogs
      fed oocysts.
AB  - Canine intestinal coccidiosis is a cause of diarrhea in young dogs and dogs that
      are immunocompromised. Reports in the literature indicate that experimental
      reproduction of clinical coccidiosis with Cystoisospora canis (syn. Isospora
      canis) is difficult, and few studies have been done with C. canis. Experimental
      oral infections were attempted in 22, 6- to 8-wk-old female beagles with 5 x
      10(4) (n = 2) or 1 x 10(5) (n = 20) sporulated C. canis oocysts. Diarrhea was
      observed in all inoculated dogs. Diarrhea began 2-3 days before oocyst excretion.
      Five of the 22 dogs were given an anticoccidial (sulfadimethoxine) because of
      their clinical signs. The mean prepatent period was 9.8 days (range, 9-11 days, n
      = 22 dogs), and the patent period was 8.9 days (range, 7-18 days, n = 20 dogs).
      Two dogs exhibiting clinical coccidiosis were examined at necropsy 10 days after
      infection. Developmental stages of C. canis were present in cells in the lamina
      propria throughout the entire small intestine in both dogs. Microscopic lesions
      observed in both of these dogs were villous atrophy, dilation of lacteals, and
      hyperplasia of lymph nodes in Peyer's patches. Results of bacterial and viral
      examinations of these 2 dogs were negative, indicating that intestinal
      coccidiosis was the cause of the diarrhea. Our study indicates that C. canis can
      be a primary cause of diarrhea in young dogs.

PMID- 17539420
TI  - New species of Moravecia (Nematoda: Dracunculoidea) from body cavity of marine
      perciform fish Percophis brasiliensis in Argentina.
AB  - A new species of dracunculoid nematode, Moravecia argentinensis n. sp.
      (Guyanemidae), is described from the blood vessels and body cavity of Brazilian
      flathead, Percophis brasiliensis Quoy et Gaimard (Perciformes: Percophidae), from
      off the coast of Argentina. The new species differs from the only other
      congeneric species, Moravecia australiensis Ribu et Lester, 2004, mainly in the
      number (14) of cephalic papillae, the length ratio of the muscular and glandular
      portions of esophagus (1:1-2), more numerous (3-5 pairs) genital papillae in the
      male, and the presence of a sclerotized copulatory plate. This is the second
      known species of Moravecia Ribu et Lester, 2004 and the first species of this
      genus reported from South American waters.

PMID- 17539421
TI  - Seven new Yorkeria species (Cestoda: Tetraphyllidea) from Borneo and Australia
      and their implications for identification of Chiloscyllium (Elasmobranchii:
      Orectolobiformes) species.
AB  - New material of Yorkeria Southwell, 1927, collected from Chiloscyllium Muller &
      Henle species, i.e., bamboo sharks, from Malaysian Borneo and eastern Australia
      was found to include specimens that appear to be consistent with, and thus allow
      redescription of, the poorly characterized type of the genus, Yorkeria parva
      Southwell, 1927, as well as 7 new species of tetraphyllidean cestodes from the
      genus Yorkeria. Discovered in Borneo were Y. parva and Yorkeria teeveeyi n. sp.
      from Chiloscyllium indicum (Gmelin), Yorkeria garneri n. sp. from Chiloscyllium
      hasselti Bleeker, Yorkeria pusillulus n. sp., Yorkeria saliputium n. sp., and
      Yorkeria yubodohensis n. sp. from Chiloscyllium punctatum Miller & Henle. In
      Australia, a shark species tentatively identified as Chiloscyllium cf. punctatum
      was found to host Yorkeria izardi n. sp. and Yorkeria longstaffae n. sp. Three of
      the new species resemble Yorkeria kelleyae Caira & Tracy, 2002, described from
      sharks identified as C. punctatum in Thailand, in their possession of medial and
      lateral hooks that are approximately equal in length. All 3 can be distinguished
      from Y. kelleyae, however, in their possession of vitelline follicles that are
      not interrupted at the level of the ovary; they differ from one another in that 1
      is hyperapolytic (Y. saliputium n. sp.), and the other 2 possess round (Y.
      pusillulus n. sp.) versus tapered (Y. longstaffae n. sp.) bothridia. Among
      species with medial and lateral hooks that are conspicuously unequal in length,
      only Y. izardi n. sp. possesses bothridia that taper posteriorly and almost
      completely overlap the cephalic peduncle, stopping just short of its posterior
      margin. Yorkeria garneri n. sp. is distinctive in its possession of mature
      proglottids that are only slightly longer than wide, rather than distinctly
      longer than wide. Particularly notable is Y. teeveeyi n. sp., which bears a
      stobila on which 2-3 of the subterminal proglottids are consistently more mature
      than the terminal proglottid. Yorkeria yubodohensis n. sp. most closely resembles
      Y. parva, differing in the pattern of microtriches seen on its scolex, and also
      in its possession of relatively fewer proglottids. This brings the total number
      of Yorkeria species described worldwide to 12. The host associations of these
      cestodes raise questions about the conspecificity of bamboo shark specimens
      identified as C. punctatum in Thailand, Borneo, and Australia, since individuals
      in each of these 3 regions appear to host distinctive, nonoverlapping Yorkeria
      faunas. A key to the 12 known species of Yorkeria is provided.

PMID- 17539422
TI  - A new Huffmanela species (Nematoda: Trichosomoididae) parasitizing atherinid
      fishes in north Patagonian Gulfs, Argentina.
AB  - Huffmanela moraveci n. sp. (Nematode: Trichosomoididae) is described from the
      skin of fins and gills of the silversides Odontesthes smitti Lahille, 1949, and
      Odontesthes nigricans Richardson, 1848 (Pisces: Atheriniformes), from
      southwestern Atlantic coast, on the basis of the morphology of adults and eggs
      found in the host tissues. Huffmanela moraveci n. sp. can be distinguished from
      Huffmanela carcharini, H. banningi, H. japonica, H. mexicana, H. paronai, H.
      schouteni, H. shikokuensis, H. branchialis, H. filamentosa, H. ossicola, and H.
      lata by the size and shape of the eggs. The adult stage of H. moraveci n. sp. can
      be differentiated from H. hufmani and H. canadensis by the position of the nerve
      ring and by the total esophagus length/body length ratio. Huffmanela moraveci n.
      sp. also differs from H. huffmani by the presence of bacillary bands and by the
      body length. This is the first report of a species of Huffmanela in South
      America, the first report of a species of Huffmanela with Odontesthes spp. as
      host, and the third known adult form in the genus.

PMID- 17539423
TI  - A new species of Syphacia (Nematoda: Oxyuridae) from Akodon azarae (Rodentia:
      Cricetidae) in Argentina.
AB  - Eight species of Syphacia (Nematoda: Oxyuridae) have been reported from South
      America in rodents of the Sigmodontinae, only 1 of which has been recorded in
      Argentina. Syphacia (Syphacia) carlitosi n. sp. is described from the ceca of
      Akodon azarae bibianae and Akodon azarae hunteri (Sigmodontinae: Akodontini)
      captured in 3 provinces in the northeast region of Argentina. The new species is
      differentiated principally by the shape of the cephalic plate; distribution of
      submedian papillae and amphids; presence, extent, and shape of cervical alae in
      females; absence of lateral alae; absence of deirids; spicular and gubernaculum
      length; shape and structure of accessory hook of gubernaculum; and distance of
      mamelons, excretory pore, and vulva from the anterior extremity. This is the
      second record of Syphacia parasitizing rodents of the tribe Akodontini.

PMID- 17539424
TI  - Acanthocephala in amphibians (Anura) and reptiles (Squamata) from Brazil and
      Paraguay with description of a new species.
AB  - In a survey of 1,732 amphibians and reptiles collected across Sao Paulo Province,
      Brazil, and 7 provinces in Paraguay, 26 species were found infected with
      acanthocephalans. Of 1,510 anurans, 14 anurans, representing 11 species, were
      infected with cystacanths of Centrorhynchus spp. and 1 anuran with cystacanths of
      Oligacanthorhynchus sp. Of 107 lizards, 1 lizard was infected with cystacanths of
      Centrorhynchus sp. and 1 lizard with cystacanths of Oligacanthorhynchus sp.
      Acanthocephalus caspanensis was found in 3 anurans (3 species) and
      Acanthocephalus lutzi in 3 anurans (2 species) and 2 snakes (2 species). The
      systematic position of A. lutzi cannot be resolved using presently available
      morphological data. Acanthocephalus saopaulensis n. sp. was found in a single
      individual of Bufo ictericus. The new species can be differentiated from all its
      congeners except A. caspanensis in having a sigmoid-shaped male posterior end and
      from A. caspanensis in having a proboscis armature of 16 rows of 5-7 hooks rather
      than 18-19 rows of 6-7 hooks and larger eggs. The status of Acanthocephalus and
      Pseudoacanthocephalus continues to be problematic.

PMID- 17539425
TI  - Neosychnocotyle maggiae, n. gen., n. sp. (Platyhelminthes: Aspidogastrea) from
      freshwater turtles in northern Australia.
AB  - Neosychnocotyle maggiae, n. gen., n. sp., (Aspidogastrea) is described from the
      pig-nosed turtle, Carettochelys insculpta, and reported from the Victoria River
      red-faced turtle, Emydura victoriae, all from the Daly River, Northern Territory,
      Australia. Neosychnocotyle n. gen. is differentiated from all aspidogastrean
      genera but one by the absence of a cirrus sac. The similar Sychnocotyle also
      lacks a cirrus sac, but Neosychnocotyle n. gen. differs from the former genus by
      possessing a narrow, tapered anterior end, a ventral disk that covers the
      posterior end of the body, a genital pore that is displaced anteriorly, and a vas
      deferens that is less convoluted and less robust. Analysis of ribosomal DNA
      sequences demonstrates substantial sequence variability between representatives
      of Sychnocotyle and Neosychnocotyle maggiae, n. gen., n. sp. It is possible that
      this new parasite may reach sexual maturity only in C. insculpta. This is only
      the second aspidogastrean species reported from Australian freshwater turtles.

PMID- 17539426
TI  - Aptorchis megacetabulus n. sp. (Platyhelminthes: Digenea) from the northern long
      necked turtle, Chelodina rugosa (Pleurodira: Chelidae), in Australia.
AB  - Aptorchis megacetabulus n. sp. is described from the intestine of the northern
      long-necked turtle, Chelodina rugosa (Pleurodira: Chelidae), in Northern
      Territory, Australia. This is the first helminth species reported from C. rugosa.
      This plagiorchioidean digenean differs from the 3 previously known species of
      Aptorchis in the relative size of the ventral sucker, overall body proportions,
      nature of the cirrus sac, and egg size. Comparison of approximately 2,700 bases
      of ribosomal DNA obtained from all known Aptorchis species strongly supports the
      status of Aptorchis megacetabulus n. sp. as a new species.

PMID- 17539427
TI  - Development of an enzyme-linked immunoelectrotransfer blot (EITB) assay using two
      baculovirus expressed recombinant antigens for diagnosis of Taenia solium
      taeniasis.
AB  - Taeniasis diagnosis is an important step in the control and elimination of both
      cysticercosis and taeniasis. We report the development of 2 serological taeniasis
      diagnostic tests using recombinant antigens rES33 and rES38 expressed by
      baculovirus in insect cells in an EITB format. In laboratory testing with defined
      sera from nonendemic areas, rES33 has a sensitivity of 98% (n = 167) and a
      specificity of 99% (n = 310) (J index: 0.97); rES38 has a sensitivity of 99% (n =
      146) and a specificity of 97% (n = 275) (J index: 0.96). Independent field
      testing in Peru showed 97% (n = 203) of the taeniasis sera were positive with
      rES33, and 100% of the nontaeniasis sera (n = 272) were negative with rES33; 98%
      (n = 198) of taeniasis sera were positive with rES38, and 91% (n = 274) of the
      nontaeniasis sera were negative with rES38. Among the Peruvian sera tested, 17 of
      26 Peruvian Taenia saginata sera were false positive with rES38 test. Both tests
      were also examined with cysticercosis sera, with a positive rate ranging from 21%
      to 46%. rES33 and rES38 tests offer sensitive and specific diagnosis of taeniasis
      and easy sample collection through finger sticks that can be used in large-scale
      studies. They are currently being used in cysticercosis elimination programs in
      Peru.

PMID- 17539428
TI  - Infection of Myxobolus galaxii (Myxozoa) in Galaxias maculatus (Osmeriformes:
      Galaxiidae) from northwestern Patagonian Andean lakes (Argentina).
AB  - The infection of Myxobolus galaxii Szidat, 1953, from the musculature and
      abdominal organs of northwestern Patagonian Galaxias maculatus is described.
      Plasmodia are histozoic and intercellular. Spores are pyriform in valvar view and
      biconvex in sutural view, with 4-9 edge notches in the sutural line, varying in
      shape within the same plasmodium. Myxobolus galaxii was detected in fish from 7
      of 17 Andean Patagonian lakes, with prevalences ranging between 2 and 17%. A
      repeating pattern of summer increment in prevalence was observed, which could be
      explained by the ontogenetic migratory movements of the fish in Lake Gutierrez.
      Also, accumulation of plasmodia through the life span of fish was detected.

PMID- 17539429
TI  - Paleoparasitological analysis of a raptor pellet from southern Patagonia.
AB  - Organic remains attributable to one regurgitated pellet were examined. The
      pellet, belonging to a bird of prey and collected from a cave of Southern
      Patagonia, was dated at 6,540 +/- 110 yr. With standard paleoparasitological
      procedures, eggs of Capillaria sp. and a mite, Demodex sp., were found. The
      parasites found in the pellet belong to a rodent ingested by the bird. The
      present report constitutes the first paleoparasitological study of a regurgitated
      pellet.

PMID- 17539430
TI  - Comparison of a manual and an automated method to estimate the number of uterine
      eggs in anisakid nematodes: to Coulter or not to Coulter. Is that the question?
AB  - Studies reporting numbers of eggs in vagina and utero in nematodes often give
      little information of the technique used for the estimations. This situation
      hampers comparison among studies, because, so far, differences in estimations
      provided by different techniques have not been assessed. This note examines
      whether a manual method based on visual counts in aliquots and an automated
      method using a Coulter counter yield equivalent estimations of egg numbers in
      vagina and utero of 3 anisakid nematode species (Anisakis simplex,
      Pseudoterranova decipiens, and Contracaecum osculatum). The number of eggs from
      50 females per nematode species was estimated using both techniques. The
      automated and manual methods yielded similar egg counts (correlation coefficients
      >0.9 in the 3 species), but the methods were not always statistically equivalent.
      The automated method was more precise and seemed less dependent on egg density,
      whereas the manual method was less time-consuming (contrary to previous
      perceptions) and less expensive. Despite the higher precision of automated
      counts, the manual technique seemed to produce similar estimates; thus, it may be
      particularly useful in developing countries where nematode parasitism is
      prevalent in humans and domestic animals, but scientific resources are limited.

PMID- 17539431
TI  - A novel Giardia duodenalis assemblage A subtype in fallow deer.
AB  - The molecular identification of species and genotypes of Giardia spp. infecting
      wild mammals represents the most reliable tool to understand the role played by
      these animals as reservoirs of cysts infectious for human and other animals. Of
      139 fecal samples collected from fallow deer (Dama dama L.) hunted in a Natural
      Reserve of northern Italy, the prevalence of Giardia sp. was 11.5% (16 of 139
      animals), and it was higher in fawns than in older animals. Fragments of the
      betagiardin and triose phosphate isomerase (tpi) genes were successfully
      polymerase chain reaction amplified and sequenced from 8 isolates. No sequence
      variation was observed between isolates at the 2 genetic loci. Sequence and
      phylogenetic analyses identified a Giardia duodenalis subtype that clusters with
      assemblage A isolates and that shows homologies of 98 and 97% at the beta-giardin
      and tpi loci, respectively, compared with the A1 subtype. Because the G.
      duodenalis subtype found in fecal samples of fallow deer has never been detected
      previously, its role as a pathogen for humans and domestic animals is unknown,
      but, considering its genetic distinctiveness, it is likely to be low.

PMID- 17539432
TI  - Immunomodulation of the response to excretory/secretory antigens of Fasciola
      hepatica by Anapsos in Balb/C mice and rat alveolar macrophages.
AB  - It is known that excretory/secretory antigens of Fasciola hepatica (ESFh) trigger
      a Th2-like immune response. Anapsos (A) is an aqueous hydrosoluble extract
      obtained from the rhizomes of the fern Polypodium leucotomos that has shown
      immunomodulator effects in some parasitic infections and immunological disorders.
      In this work we assess the effect of Anapsos and ESFh and Quillaja saponaria
      extract (Qs) on BALB/c mice and rat alveolar macrophages. Anapsos modulates the
      response of mice immunized with ESFh, decreasing IgG antibodies in A+ESFh- and
      A+Qs+ESFh-treated mice and triggering high levels of gammaIFN in spleen cell
      culture in comparison with ESFh- and Qs + ESFh--treated groups. Moreover, Anapsos
      showed statistically significant inhibitory effects on the nitrite production by
      rat alveolar macrophages prestimulated with lipopolysaccharide (LPS) as well as
      ESFh antigen in comparison with macrophages stimulated only with LPS. The
      application of ESFh and Anapsos combined avoids this inhibitory effect. Thus,
      Anapsos modulates the immune response against ESFh in naive mice and on the
      nitrite production in prestimulated rat aveolar macrophages.

PMID- 17539433
TI  - Experimental infection of Dirofilaria immitis in raccoon dogs.
AB  - Canine heartworm (Dirofilaria immitis) is a nematode that naturally parasitizes
      in the pulmonary arteries and the right ventricle of domestic dogs (Canis
      familiaris) as final hosts. Japanese raccoon dogs (Nyctereutes procyonoides
      viverrinus) also are known to be susceptible to infection by the parasite.
      However, prevalence of this infection among free-ranging raccoon dogs is low and
      so is the worm burden. To examine the susceptibility of the raccoon dog to D.
      immitis infection, 3 raccoon dogs and 2 beagles were inoculated 4 times with 25
      third-stage larvae (L3s) of D. immitis at 3-wk intervals. Worms were recovered
      from 2 raccoon dogs and both domestic dogs. The average percentage of recovery
      (2.3%) of the raccoon dogs was almost 10 times lower (24.5%) than that of the
      domestic dogs, but there was no significant difference in the body length of
      worms recovered from 2 types of hosts. To examine microfilaremia, 2 raccoon dogs
      were infected with 100 L3s. Microfilaremia was observed for 180 days
      postinoculation (PI) but disappeared at about 300 days PI. The raccoon dog was
      mildly susceptible to infection with D. immitis, but surviving worms developed
      and matured normally.

PMID- 17539434
TI  - A rapid method for producing highly purified Cryptosporidium parvum oocysts.
AB  - Most procedures that have been described for purifying Cryptosporidium parvum
      oocysts are designed to either identify the parasites in clinical specimens or
      isolate oocysts from a small volume of feces from infected animals. The present
      study describes a rapid method for purifying high numbers of C. parvum oocysts
      from feces of infected calves that contains minimal contaminating fecal material
      and bacteria. The isolation method is based on differential flotation of C.
      parvum oocysts in NaCl, followed by ether extraction to solubilize lipids in calf
      feces. This procedure regularly yields > 10(9) purified C. parvum oocysts within
      1-2 days of feces collection.

PMID- 17539435
TI  - Infection dynamics of Centrocestus armatus cercariae (Digenea: Heterophyidae) to
      second intermediate fish hosts.
AB  - The infection dynamics of Centrocestus armatus cercariae with respect to second
      intermediate fish hosts were investigated using cercariae collected from
      naturally infected Semisulcospira libertina. Cercariae survival and infectivity
      were recorded at 2-hr intervals. Survival remained constant but decreased
      abruptly at 30 hr of age. An age-dependent model presented the best-fit curve for
      the survival data (r2 0.936), implying that cercariae tended to allocate
      resources equally among themselves and then died once those resources were
      depleted. Cercariae infectivity remained constant over the first 10 hr of life
      and then declined; an age-dependent model also provided a better fit (r2 =
      0.956). The transmission rate of C. armatus cercariae to the fish host was
      relatively low near the time of emergence from the snail host but peaked at 85%
      after 1 hr and then maintained a plateau period until 5 hr of exposure to fish.
      The pattern of transmission was also investigated initially at varying densities
      of cercariae and then by maintaining a constant cercariae density but varying the
      total number. Results revealed that the pattern of transmission was frequency
      dependent.

PMID- 17539436
TI  - Giardia sp. and Cryptosporidium sp. infections in primates in fragmented and
      undisturbed forest in western Uganda.
AB  - In June 2005, we collected 115 fecal samples from wild primates in western Uganda
      and examined them for Cryptosporidium sp. and Giardia sp. with the use of
      immunofluorescent antibody (IFA) detection. We sampled primates from an
      undisturbed forest in Kibale National Park and from 3 highly disturbed forest
      fragments outside the park. Of disturbed forest samples, red colobus (Pilocolobus
      tephrosceles) and red-tailed guenons (Cercopithecus ascanius) harbored species of
      Cryptosporidium or Giardia, but black-and-white colobus (Colobus guereza) did
      not. All primate samples from undisturbed forest were negative for both
      parasites. Seven of 35 (20%) red colobus and 1 of 20 red-tailed guenons (5%) from
      forest fragments were infected with either Cryptosporidium sp. or Giardia sp. The
      presence of Cryptosporidium and Giardia species in primates living in forest
      fragments, but not in primates in undisturbed forest, suggests that habitat
      disturbance may play a role in transmission or persistence of these pathogens.

PMID- 17539437
TI  - Human pseudoterranovosis, an emerging infection in Chile.
AB  - Fifteen cases of human pseudoterranovosis are reported for Chile, representing an
      emerging parasitic infection in this country caused by larvae of the nematode
      Pseudoterranova sp. Our observations also included an outbreak of
      pseudoterranovosis in 3 of 4 individuals who shared the same raw fish dish
      (cebiche). Most of the cases occurred in adult patients. The main source of
      infection was from consumption raw or fried marine fish, including hakes
      (Merluccius australis or Merlucciuts gayi), pomfret (Brama australis), Inca scad
      (Trachurus murphvi), and corvina (Cilus gilberti). Seasonal distribution showed
      most of the cases to occur in fall and spring. Parasite larvae were isolated from
      the mouths of most of the patients after they reported a pharyngeal tickling
      sensation, coughing, vomiting, or a foreign body in the mouth or throat.

PMID- 17539438
TI  - Concurrent exercise and muscle protein synthesis: implications for exercise
      countermeasures in space.
AB  - INTRODUCTION: Exercise countermeasures for long duration space crews incorporate
      aerobic and resistance exercise (i.e., concurrent training). Microgravity
      simulation studies show that resistance exercise alone can be completely
      effective at preventing muscle loss, yet crews return from missions with reduced
      muscle mass and function. Some Earth-based studies show human skeletal muscle
      size and strength increases typically noted with resistance training are blunted
      when aerobic and resistance training are performed concurrently. The purpose of
      this study was to determine if the addition of aerobic exercise prior to
      performing resistance exercise blunts the acute anabolic response to resistance
      exercise. METHODS: Myofibrillar protein synthesis rates were determined in 12
      individuals (6 men, 6 women, 26 +/- 2 yr) by measuring the incorporation of
      [2H5]phenylalanine into vastus lateralis muscle protein following resistance
      exercise (4 sets of 10 repetitions of both leg press and leg extension) and
      following resistance exercise that had been preceded by 90 min of strenuous
      aerobic cycling exercise. RESULTS: Myofibrillar protein synthesis following
      resistance exercise (0.092 +/- 0.006% x h(-1)) was not suppressed (p > 0.05)
      compared with following concurrent exercise (0.100 +/- 0.007% x h(-1)).
      DISCUSSION: It appears the anabolic response to resistance exercise cannot
      explain the attenuated muscle mass and strength gains imposed by chronic
      concurrent aerobic and resistance training, nor the response of space crews to in
      flight concurrent countermeasures. These findings have important implications for
      future optimization of the concurrent aerobic and resistance exercise
      countermeasures for long duration space crews.

PMID- 17539439
TI  - Head rotation during upright tilt increases cardiovagal baroreflex sensitivity.
AB  - INTRODUCTION: Vestibular activation of semicircular canals has been linked to
      increased activity of parasympathetic neurons and has been proposed as a
      contributing factor to orthostatic intolerance. However, the functional
      consequences of head yaw rotation during orthostasis on human autonomic function
      have not been documented. The purpose of this study was to determine the effects
      of voluntary head rotation on autonomic function during upright tilt. METHODS:
      ECG, beat-by-beat finger arterial pressure, respiratory rate, PetCO2, and
      cerebral blood flow velocity were recorded in 10 healthy subjects. Subjects were
      studied supine and during two separate 5-min periods of upright tilt to 70
      degrees with and without continuous head yaw rotation (180 degrees at 0.25 Hz).
      Breathing frequency was controlled strictly at 0.25 Hz during each trial and data
      were analyzed in both time and frequency domains. Cross-spectral techniques
      (transfer functions) were used to assess cardiovagal baroreflex sensitivity and
      dynamic cerebral autoregulation. RESULTS: Head rotation during upright tilt
      increased transfer function magnitude between systolic pressure and R-R interval
      at the low frequency (0.04-0.15 Hz) from 8.1 +/- 2.3 to 10.4 +/- 1.6 ms x mmHg(
      1) (p = 0.04), but did not affect estimates of vagal-cardiac efferent activity or
      cerebral blood flow velocity, hemodynamic oscillations, or dynamic cerebral
      autoregulation. CONCLUSIONS: Increased cardiovagal baroreflex sensitivity in
      conjunction with preserved cerebral autoregulation suggests that head rotation
      during upright tilt is unlikely to trigger orthostatic instability in normal,
      healthy humans.

PMID- 17539440
TI  - Simulator-induced spatial disorientation: effects of age, sleep deprivation, and
      type of conflict.
AB  - INTRODUCTION: Spatial disorientation mishaps are greater at night and with
      greater time on task, and sleep deprivation is known to decrease cognitive and
      overall flight performance. However, the ability to perceive and to be influenced
      by physiologically appropriate simulated SD conflicts has not previously been
      studied in an automated simulator flight profile. METHODS: A set of 10 flight
      profiles were flown by 10 U.S. Air Force (USAF) pilots over a period of 28 h in a
      specially designed flight simulator for spatial disorientation research and
      training. Of the 10 flights, 4 had a total of 7 spatial disorientation (SD)
      conflicts inserted into each of them, 5 simulating motion illusions and 2
      involving visual illusions. The percentage of conflict reports was measured along
      with the effects of four conflicts on flight performance. RESULTS: The results
      showed that, with one exception, all motion conflicts were reported over 60% of
      the time, whereas the two visual illusions were reported on average only 25% of
      the time, although they both significantly affected flight performance. Pilots
      older than 35 yr of age were more likely to report conflicts than were those
      under 30 yr of age (63% vs. 38%), whereas fatigue had little effect overall on
      either recognized or unrecognized SD. DISCUSSION: The overall effects of these
      conflicts on perception and performance were generally not altered by sleep
      deprivation, despite clear indications of fatigue in our pilots.

PMID- 17539441
TI  - Neck exercises compared to muscle activation during aerial combat maneuvers.
AB  - INTRODUCTION: Performing specific neck strengthening exercises has been proposed
      to decrease the incidence of neck injury and pain in high performance combat
      pilots. However, there is little known about these exercises in comparison to the
      demands on the neck musculature in flight. METHODS: Eight male non-pilots
      performed specific neck exercises using two different modalities (elastic band
      and resistance machine) at six different intensities in flexion, extension, and
      lateral bending. Six Royal Australian Air Force Hawk pilots flew a sortie that
      included combinations of three +Gz levels and four head positions. Surface
      electromyography (EMG) from selected neck and shoulder muscles was recorded in
      both activities. RESULTS: Muscle activation levels recorded during the three
      elastic band exercises were similar to in-flight EMG collected at +1 Gz (15%
      MVIC). EMG levels elicited during the 50% resistance machine exercises were
      between the +3 Gz (9-40% MVIC) and +5 Gz (16-53% MVIC) ranges of muscle
      activations in most muscles. EMG recorded during 70% and 90% resistance machine
      exercises were generally higher than in-flight EMG at +5 Gz. DISCUSSION: Elastic
      band exercises could possibly be useful to pilots who fly low +Gz missions while
      50% resistance machine mimicked neck loads experienced by combat pilots flying
      high +Gz ACM. The 70% and 90% resistance machine intensities are known to
      optimize maximal strength but should be administered with care because of the
      unknown spinal loads and diminished muscle force generating capacity after
      exercise.

PMID- 17539442
TI  - Discontinuous growth modeling of adaptation to sleep setting changes: individual
      differences and age.
AB  - INTRODUCTION: Biomedical devices allow investigators to collect long-term
      repeated measures data to study adaptation. We examined 26 d of actigraph sleep
      data and tested for individual differences in sleep patterns prior to, during,
      and after a transition of sleeping in garrison to sleeping in a field exercise
      setting. In addition, we examined whether the individual difference variable of
      participant age (a continuous variable ranging from 19-29 yr) was related to
      sleep patterns. METHODS: Actigraph data was obtained from 77 cadets participating
      in a month-long military training program. At day 17, participants transitioned
      from sleeping in garrison to sleeping in a field exercise setting. A
      discontinuous growth model tested for individual differences in 1) overall sleep
      time, 2) garrison sleep slope, 3) the transition, and 4) the sleep slope during
      the field exercise setting. RESULTS: Individuals varied significantly in their
      overall sleep time, pattern of sleep in garrison, and the degree to which sleep
      decreased at the transition. The decline in sleep at the transition was related
      to participant age such that increases in age were associated with larger
      declines in sleep minutes. DISCUSSION: Individuals display significant
      variability in sleep patterns that can be detected using discontinuous growth
      models. The individual difference variable of participant age explains some of
      this variability. Much of the variability, however, remains unexplained. Future
      work will benefit from using discontinuous growth models to identify and model
      individual difference variables such as age when examining response patterns and
      transitions in data collected in applied field settings.

PMID- 17539443
TI  - Risk factors for venous gas emboli after decompression from prolonged hyperbaric
      exposures.
AB  - INTRODUCTION: The physical forces governing gas phase nucleation and growth in a
      liquid would predict less variation in the development of decompression sickness
      (DCS) than is known to occur in people. METHODS: In order to gain insight into
      the causes of biological susceptibility to DCS, we analyzed a dataset containing
      250 human steady-state hyperbaric exposures using multivariate ordinal and linear
      regression analysis for relationships between venous gas emboli (VGE) and
      exposure parameters and subject characteristics. RESULTS: In both previously
      published data and new chamber exposure data, we found that the strongest
      predictor of VGE magnitude after decompression was the duration and depth of the
      hyperbaric exposure, as predicted. Of the subject factors, only age was
      significantly associated with VGE; body mass index (BMI) and gender were not. The
      relationship between age and VGE strengthened with decompression magnitude.
      DISCUSSION: These results suggest that the physiology of aging interacts with the
      mechanism of VGE generation, altering the risk of DCS after decompression.

PMID- 17539444
TI  - Echocardiography in military oxygen divers.
AB  - BACKGROUND: Oxygen divers undergo environmental stressors such as immersion,
      ventilation with scuba, cold exposure, and increased ambient pressure. All of
      these stressors may be responsible for acute hemodynamic modifications. We
      hypothesized that repeated hyperbaric hyperoxia exposure induces long-term
      cardiovascular modifications. METHODS: A Doppler echocardiography was conducted
      on 20 military oxygen divers (average 12 yr diving experience) and compared with
      22 controls. Parameters known to be modified by acute hyperoxic exposure, such as
      left ventricular (LV) function (systolic and diastolic) and arterial compliance,
      were analyzed. RESULTS: Controls and divers were matched appropriately for age
      and height, although the divers had a higher body mass index and aerobic
      capacity. Left atrial and left ventricular diameters did not differ between the
      two groups. On the other hand, left ventricular mass was significantly higher in
      the elite military divers (209 +/- 43 g) in comparison with the control group
      (172 +/- 48 g), even when LV mass was indexed to body surface area. Left
      ventricular systolic and diastolic function indices, stroke volume, cardiac
      index, peripheral vascular resistance, and systemic compliance were comparable
      between the two groups. CONCLUSION: A greater LV mass was observed in oxygen
      military divers. The echocardiographic differences between divers and controls
      could be attributed to the high level physical training undertaken by the
      military divers. Some stressors, such as cold water immersion, repeated hyperoxic
      exposures, scuba breathing, and long distance swimming, could have participated
      to the echocardiographic findings in oxygen divers.

PMID- 17539445
TI  - Hyperventilation in a motion sickness desensitization program.
AB  - INTRODUCTION: In motion sickness desensitization programs, the motion sickness
      provocative stimulus is often a forward bending of the trunk on a rotating chair,
      inducing Coriolis effects. Since respiratory relaxation techniques are applied
      successfully in these courses, we investigated whether these repetitive trunk
      movements by themselves may induce hyperventilation and consequently add to the
      motion sickness. METHODS: There were 12 healthy subjects who participated in our
      study. In the Baseline condition, subjects sat relaxed on the stationary chair.
      In the Hypervent condition, subjects performed voluntary hyperventilation (the
      level was prescribed). In two other conditions subjects rhythmically bent their
      trunk on a stationary chair (Tilt-Stat condition) and on a rotating chair (Tilt
      Rot condition). In all conditions we measured respiratory and cardiovascular
      activity (heart frequency, tidal volume, end-tidal CO2, and respiration
      frequency). RESULTS: Of the 12 subjects, 9 had to stop prematurely in the Tilt
      Rot condition because of moderate nausea. Except for heart rate in the Tilt-Rot
      condition, the measured physiological parameters in these subjects in the Tilt
      Stat and Tilt-Rot conditions were not statistically different from the Baseline
      condition. Only in the Hypervent condition were significant differences observed,
      but no nausea. DISCUSSION: The findings show that hyperventilation is not the
      main cause of nausea during the Coriolis effects. We conclude that during the
      pilot desensitization program with Coriolis stimuli, measurement of
      cardiovascular and respiratory parameters is not necessary; however, in those
      cases that do not respond to the intervention, we recommend paying attention to
      respiratory parameters because hyperventilation does occur on an individual
      basis.

PMID- 17539446
TI  - Alcohol violations and aviation accidents: findings from the U.S. mandatory
      alcohol testing program.
AB  - INTRODUCTION: Mandatory alcohol testing has been implemented in the U.S. aviation
      industry since 1995. This study documents the prevalence of alcohol violations
      and the association between alcohol violations and aviation accidents among
      aviation employees with safety-sensitive functions. METHODS: Data from the random
      alcohol testing and post-accident alcohol testing programs reported by major
      airlines to the Federal Aviation Administration for the years 1995 through 2002
      were analyzed. A violation was defined as an alcohol level of > or = 0.04% or a
      refusal to submit to testing. Relative and attributable risks of accident
      involvement associated with alcohol violations were estimated using the case
      control method. RESULTS: During the study period, random alcohol testing yielded
      a total of 440 violations, with an overall prevalence rate of 0.09% and a
      prevalence rate of 0.03% for flight crews. Alcohol violations were associated
      with an increased yet not statistically significant risk of accident involvement
      (odds ratio 2.56, 95% confidence interval 0.81-7.08) and were attributed to 0.13%
      of aviation accidents. DISCUSSION: Alcohol violations among U.S. major airline
      employees with safety-sensitive functions are rare and play a negligible role in
      aviation accidents.

PMID- 17539447
TI  - First-generation H1 antihistamines found in pilot fatalities of civil aviation
      accidents, 1990-2005.
AB  - INTRODUCTION: First-generation H1-receptor antagonists are popularly used for
      alleviating allergy and cold symptoms, but these antihistaminics cause drowsiness
      and sedation. Such side effects could impair performance and, thus, could be the
      cause or a factor in accidents. Therefore, the prevalence of these antagonists
      was evaluated in aviation accident pilot fatalities. METHODS: The Civil Aerospace
      Medical Institute's (CAMI's) Toxicology Database was examined for the presence of
      the first-generation antihistamines in pilot fatalities of civil aircraft
      accidents that occurred during a 16-yr (1990-2005) period. RESULTS: Of 5383 fatal
      aviation accidents from which CAMI received specimens, there were 338 accidents
      wherein pilot fatalities (cases) were found to contain brompheniramine,
      chlorpheniramine, diphenhydramine, doxylamine, pheniramine, phenyltoloxamine,
      promethazine, and triprolidine. Of the 338 accidents, 304 were general aviation
      accidents, and 175 of the 338 pilots held private pilot airman certificates.
      Antihistamines were detected alone in 103 fatalities (1 antihistamine in 94 and 2
      antihistamines in 9), while other drug(s) and/or ethanol were also present in an
      additional 235 fatalities. The antihistamines were found in approximately 4 and
      11% of the fatalities/accidents in 1990 and in 2004, respectively. The use of
      antihistamine(s) was determined by the National Transportation Safety Board to be
      the cause of 13 and a factor in 50 of the 338 accidents. CONCLUSIONS: There was
      an overall increasing trend in the use of antihistamines by aviators during the
      16-yr span. Blood levels of the antihistaminics were in the sub-therapeutic to
      toxic range. Findings from this study will be useful in investigating future
      accidents involving antihistamines.

PMID- 17539448
TI  - Cold injury to a diver's hand after a 90-min dive in 6 degrees C water.
AB  - We present here a case of non-freezing cold injury (NFCI) in a sport scuba diver.
      There are similarities between the presenting symptoms of NFCI and decompression
      sickness, e.g., pain and/or altered sensation in an extremity, often reported as
      numbness. In both conditions patients have been known to describe their lower
      limbs or feet as feeling woolly. Both conditions are the result of environmental
      exposure. Additionally, there are no good (high sensitivity and specificity)
      diagnostic tests for either condition. Diagnosis is made based on patient
      history, clinical presentation, and examination. NFCI is most frequently seen in
      military personnel, explorers, and the homeless. When affecting the feet of
      soldiers it is often referred to as "trench foot." Historically, NFCI has been
      and continues to be of critical importance in infantry warfare in cold and wet
      environments. A high priority should be given to prevention of NFCI during
      military operational planning. With the advent of so-called "technical diving"
      characterized by going deeper for longer (often in cold water) and adventure
      tourism, this extremely painful condition is likely to increase in prevalence.
      NFCI is treated symptomatically.

PMID- 17539449
TI  - Personality influences on a two-man Arctic expedition, impact on spouse, and the
      return home.
AB  - INTRODUCTION: Two men engaged in a kayak/sled Arctic expedition and their wives
      were evaluated. This report focuses on personality factors and decisions on the
      ice, psychosocial effects on those left behind, and the family re-integration
      process. METHOD: Pre-expedition measures included the Multidimensional
      Personality Inventory (MPQ) and the Personal Assessment of Intimacy in
      Relationships (PAIR). Semi-structured interviews were conducted post-expedition
      and at a 4-mo follow-up. The PAIR was re-administered at the 4-mo follow-up.
      RESULTS: Significant tension and lack of communication between the two
      expeditioners was reported in response to the leader's decision to terminate the
      expedition because of weather conditions and poor progress. The incompatibility
      of the personality traits and goals of the two expeditioners contributed to this
      tension. The wives provided positive social support to each other, although the
      support and concern of their community became stressful. For each couple, both
      positive and negative changes in partner relationship intimacy were evident at
      the 4-mo follow-up. There was little consistency between each spouse on the types
      of changes that occurred. DISCUSSION: Greater attention to and planning for the
      re-integration process is suggested, with application for the return from other
      types of challenging endeavors.

PMID- 17539450
TI  - Migraine headaches and cerebrovascular accident secondary to patent foramen
      ovale.
AB  - Atrial septal defects are a frequent finding in young persons with strokes. New
      research now suggests migraines with aura may also be associated with these types
      of cardiac defects and that surgical treatment may result in a decrease or
      resolution of migraines. This case emphasizes the importance of a thorough
      evaluation of airmen with migraines, particularly migraines with aura.

PMID- 17539451
TI  - You're the flight surgeon: Henoch-Schoenlein purpura.

PMID- 17539452
TI  - Open source software in research.

PMID- 17539453
TI  - Commercial human spaceflight: the new challenge for aerospace medicine.

PMID- 17539454
TI  - HSI for dummies.

PMID- 17539455
TI  - Public, payers focus on home health, nursing home care. Current projects aim to
      improve care, quality of life.

PMID- 17539456
TI  - Important first chance.

PMID- 17539457
TI  - Medical student section.

PMID- 17539458
TI  - Silver bullets and shotguns in lymphedema therapy.

PMID- 17539459
TI  - Integrated management of filarial lymphedema for rural communities.
AB  - The Global Alliance for the Elimination of Lymphatic Filariasis (GAELF) has
      recommended exploring local health traditions of skin care and a low cost
      treatment paradigm for rural communities has been proposed by Vaqas and Ryan. Our
      case study incorporates these promising treatments for use in treating filariasis
      in rural communities. Patients having lymphedema of one or both lower limbs
      (skin: normal, thickened or with trophic/warty changes) received treatment
      components from ayurveda, yoga and biomedicine simultaneously: including soap
      wash, phanta soaking, Indian manual lymph drainage (IMLD), pre- and post-IMLD
      yoga exercises, and compression using bandages for 194 days, along with diet
      restrictions and oral herbal medicines indicated for "elephantiasis" in Ayurveda.
      Entry points when infected were treated with biomedical drugs. The study was
      conducted in the reverse pharmacology design. 112 patients and 149 lower limbs
      completed 194 days of treatment during 2003-2006. Significant improvements were
      observed in the limb circumference measurements and the frequency of acute
      dermatolymphangioadenitis, use of preventive antibiotics, and reduction in the
      number of entry points were also improved. The objective to obtain significant
      benefit for a common problem using locally available, sustainable and affordable
      means has been achieved. It has not been our purpose to show that the regimen
      employed is better than another but the results do pose the question--"Are there
      components of Ayurvedic medicine that deserve further study?" It is important to
      understand that the regimen has been delivered mostly at home and that
      participants we have treated, representing a population suffering from a common
      problem, have not had access to effective conservative therapy that is culturally
      acceptable, safe, and efficacious.

PMID- 17539460
TI  - Culture of smooth muscle cells from guinea pig mesenteric lymphatic vessels.
AB  - The in vitro culture of lymphatic smooth muscle cells (SMCs) is a crucial step in
      studying their function and involvement in disease. Yet there is no efficient
      approach available so far because of the difficulties posed by the small size of
      most lymphatic vessels. We present a simple yet efficient method for isolating
      and culturing SMCs of collecting lymphatic vessels from guinea pig mesenteric
      tissue. In our approach, thin lymphatic vessels were digested twice from
      adventitia to media to release SMCs, which were then cultured by traditional
      methods. The lymphatic SMCs we cultured did not exhibit contact inhibition and
      demonstrated typical SMCs characteristics under light microscope, electron
      microscope and by immunohistochemical studies. This method is applicable to the
      culturing of lymphatic SMCs from other organs and provides useful materials for
      physiological and pathological lymphatic studies.

PMID- 17539461
TI  - Functional magnetic resonance evidence of cortical alterations in a case of
      reversible congenital lymphedema of the lower limb: a pilot study.
AB  - We report the first application of brain functional Magnetic Resonance Imaging
      (fMRI) to congenital peripheral lymphedema patients before and after
      microsurgical treatment. Our aim was to evaluate the effects of limb shape change
      on cortical organization of the motor system and how the cortical sensorimotor
      network restructures after microsurgical therapy. We acquired fMRI during active
      motor and motor imagery tasks before surgery and six months after surgery in a
      patient with congenital lymphedema of the left leg. fMRI data revealed activation
      differences in primary and secondary motor areas between the two scanning
      sessions for both tasks and also between the patient's and a healthy volunteer's
      activations. We suggest that these alterations could be related to changes in
      body schema representation due to the congenital lymphedema.

PMID- 17539462
TI  - Reliability and limits of agreement of circumferential, water displacement, and
      optoelectronic volumetry in the measurement of upper limb lymphedema.
AB  - We conducted a reliability comparison study to determine the intrarater and inter
      rater reliability and the limits of agreement of the volume estimated by
      circumferential measurements using the frustum sign method and the disk model
      method, by water displacement volumetry, and by infrared optoelectronic volumetry
      in the assessment of upper limb lymphedema. Thirty women with lymphedema
      following axillary lymph node dissection surgery for breast cancer surgery were
      enrolled. In each patient, the volumes of the upper limbs were estimated by three
      physical therapists using circumference measurements, water displacement and
      optoelectronic volumetry. One of the physical therapists performed each measure
      twice. Intraclass correlation coefficients (ICCs), relative differences, and
      limits of agreement were determined. Intrarater and interrater reliability ICCs
      ranged from 0.94 to 1. Intrarater relative differences were 1.9% for the disk
      model method, 3.2% for the frustum sign model method, 2.9% for water displacement
      volumetry, and 1.5% for optoelectronic volumetry. Intrarater reliability was
      always better than interrater, except for the optoelectronic method. Intrarater
      and interrater limits of agreement were calculated for each technique. The disk
      model method and optoelectronic volumetry had better reliability than the frustum
      sign method and water displacement volumetry, which is usually considered to be
      the gold standard. In terms of low-cost, simplicity, and reliability, we
      recommend the disk model method as the method of choice in clinical practice.
      Since intrarater reliability was always better than interrater reliability
      (except for optoelectronic volumetry), patients should therefore, ideally, always
      be evaluated by the same therapist. Additionally, the limits of agreement must be
      taken into account when determining the response of a patient to treatment.

PMID- 17539463
TI  - Comparison of upper limb volume measurement techniques and arm symptoms between
      healthy volunteers and individuals with known lymphedema.
AB  - Lymphedema is a problem for breast cancer survivors. The proliferation of limb
      measurement techniques makes it difficult to know how best to measure an at-risk
      limb. Using a sample of healthy volunteers and individuals with lymphedema, this
      study: 1) examined the relationship between more commonly used circumferential
      limb measurement methods and newer measurement methods of infrared laser
      perometry and bioelectrical impedance; 2) compared self-reported arm symptoms in
      healthy volunteers and breast cancer survivors with known lymphedema; and 3)
      explored the relationships among self-reported arm symptoms and circumferential
      tape measurement, infrared laser (perometry), and single and multi-frequency
      bioelectrical impedance. Lymphedema index ratios were calculated to allow
      comparison among measurement methods. Measurement methods correlated strongly
      with each other. Fourteen symptoms were reported by one or more participants in
      the lymphedema group while participants in the healthy volunteer group reported
      only eight symptoms over the same time frames. Using p < 0.001, all measurement
      methods correlated with self-reported arm swelling in the past year, while only
      circumferential and impedance measurements correlated with firmness. Future
      research needs to include serial arm measurements to explore arm volume variation
      in healthy and lymphedema volunteers and to further investigate possible
      lymphedema index ratios cut points as lymphedema diagnostic criteria.

PMID- 17539464
TI  - Lymph nodo-venous shunt in the treatment of protein losing enteropathy and
      lymphedema of leg and scrotum.
AB  - Protein Losing Enteropathy (PLE) is a syndrome associated with several diseases
      affecting the gastrointestinal system. Recent comprehensive reviews can be found
      in eMedicine and Gastroenterology. Treatment by surgery, lympho-venous
      anastomosis, excision of lymphangiectatic small bowel and gastrectomy and
      transplantation of the small intestine, depending upon the cause, have all been
      reported. We obtained a successful result for PLE associated with peripheral
      lymphedema by combining several sequential operative approaches including lymph
      nodo- venous shunt in the groin and reduction surgery for edema of the left leg
      and scrotum.

PMID- 17539465
TI  - Cosmetic neurology and cosmetic surgery: parallels, predictions, and challenges.

PMID- 17539466
TI  - Perspectives on memory manipulation: using beta-blockers to cure post-traumatic
      stress disorder.

PMID- 17539467
TI  - Pediatric neuroimaging ethics.

PMID- 17539468
TI  - Severe brain injury: recognizing the limits of treatment and exploring the
      frontiers of research.

PMID- 17539469
TI  - Policy implications of the new neuroscience.

PMID- 17539470
TI  - Internet marketing of neuroproducts: new practices and healthcare policy
      challenges.

PMID- 17539471
TI  - Chimera research and stem cell therapies for human neurodegenerative disorders.

PMID- 17539472
TI  - Gene maps, brain scans, and psychiatric nosology.

PMID- 17539473
TI  - Anthropological challenges raised by neuroscience: some ethical reflections.

PMID- 17539474
TI  - CQ sources/bibliography.

PMID- 17539475
TI  - The bodily incorporation of mechanical devices: ethical and religious issues
      (part 1).

PMID- 17539476
TI  - Probability potentiality.

PMID- 17539477
TI  - Plasma, red blood cells phospholipids and clinical evaluation after long chain
      omega-3 supplementation in children with attention deficit hyperactivity disorder
      (ADHD).
AB  - Omega-3 and omega-6 long-chain polyunsaturated fatty acids (LCPUFAs), are crucial
      to brain development and function. Increasing evidence indicates that
      deficiencies or metabolic imbalances of these fatty acids might be associated
      with childhood developmental and psychiatric disorders including attention
      deficit/hyperactivity disorder (ADHD). Omega-3 are often lacking on modern diets.
      Moreover preliminary evidences suggest that supplementation with omega-3 LCPUFAs,
      might help in the management of the ADHD linked behavioural and learning
      difficulties. However, few studies published to date have involved different
      populations, study designs, treatments and outcome results. Thus, further
      researches are required to assess the durability of the treatment effects, to
      determine optimal composition and dosages of the supplement and to develop
      reliable ways to identify patients that might have some benefits from this kind
      of treatment, also because the study of LCPUFAs and their metabolism might offer
      new approaches to the early identification and management of ADHD. In this paper,
      we provide new insight on the lipid pattern in plasma and red blood cells (RBC)
      phospholipids, together with evaluation of the arachidonic acid
      (AA)/eicosapentaenoic acid (EPA) ratio which seems to correlate with the
      improvement of the patients both from a biochemical and clinical point of view.

PMID- 17539478
TI  - Attenuation of restraint-induced behavioral deficits and serotonergic responses
      by stabilized rice bran in rats.
AB  - This study examined the effects of stabilized-rice bran (SRB) rich diet on
      responses to stress in rats. Standard rodent diet mixed with SRB in the ratio of
      2:1 and 1:1 (w/w) was given for 6 weeks to test rats. Results showed that weekly
      cumulative food intakes smaller in SRB rich diet treated animals were normalized
      at the end of the treatment. Body weights decreased and exploratory activity in
      an open field increased in SRB rich diet treated animals. Learning and espatial
      memory monitored in the Morris water test was enhanced. An episode of 2 h
      restraint stress decreased food intake of SRB as well as normal diet treated
      animals. Deficits were smaller in SRB diet than normal diet treated animals.
      Exposure to 2 h restraint stress increased brain serotonin (5-hydroxytryptamine,
      5-HT) metabolism. The increases were smaller in SRB rich than normal diet treated
      animals. A potential use of SRB in health and disease is discussed in the context
      of its antioxidant and serotonergic effect.

PMID- 17539479
TI  - Early undernourishment interferes with the maternal aggressive response triggered
      by an intruder entering the homing cage.
AB  - The maternal aggressive response (MAR) against intruders is temporarily expressed
      during lactation in association with the rearing and protection of offspring to
      promote their survival and growth in the nest. This normal component of maternal
      behaviour requires both the hormonal changes occurring at the end of pregnancy
      and the presence of pups for its establishment. Because early food restriction in
      the rat results in long-term maternal deficiencies, we analysed in Wistar rats
      the effects of perinatal undernutrition on the MAR to an intruder at days 1, 4,
      and 8 postpartum. The data showed that undernourished dams exhibited significant
      reductions of sniffing frequency on days 4 and 8 and significant increases of
      biting on day 4 and of lateral attacks on postpartum days 4 and 8. The finding of
      an altered MAR during the lactating period may be relevant for the survival and
      long-term behavioural development of the progeny.

PMID- 17539480
TI  - Early postnatal protein malnutrition causes resistance to the anxiolytic effects
      of diazepam as assessed by the fear-potentiated startle test.
AB  - Given that protein malnutrition induces structural, neurochemical and functional
      changes in the CNS, the present study aimed to investigate the effects of
      different early periods of protein malnutrition on the behavior and reactivity to
      diazepam (DZ) in a model of anxiety: the fear-potentiated startle (FPS). Male
      Wistar rats (n = 110) from well-nourished (16 %-protein) or malnourished (6%
      protein) litters were distributed in five different groups: W (well-nourished),
      M7 (malnourished for 7-days, since day 0), M14 (14-days), M21 (21-days) and M28
      (28-days). The results obtained in FPS revealed that malnourished-animals
      acquired the startle response, irrespective of the time they were exposed to the
      diet. Besides, DZ reduced the startle amplitude in the noise-alone and light
      noise trials. The data concerning the total freezing time showed that the
      expression of this response was affected by malnutrition and varied in accordance
      with the findings of previous studies in which malnutrition procedures was
      imposed for long periods (more than 50 days). Therefore, we suggest that early
      protein malnutrition: (a) did not produce deficits in the associative learning
      process of these animals in the FPS, and (b) decreased freezing time in the FPS
      and produce hyporeactivity to the effects of DZ in rats malnourished for 21 days
      or more, indicating alterations in the GABAergic neurotransmitter system.

PMID- 17539481
TI  - High dietary cholesterol facilitates classical conditioning of the rabbit's
      nictitating membrane response.
AB  - Studies have shown that modifying dietary cholesterol may improve learning and
      that serum cholesterol levels can be positively correlated with cognitive
      performance. Rabbits fed a 0, 0.5, 1 or 2% cholesterol diet for eight weeks and
      0.12 ppm copper added to their drinking water received trace and then delay
      classical conditioning pairing tone with corneal air puff during which movement
      of the nictitating membrane (NM) across the eye was monitored. We found that the
      level of classical conditioning and conditioning-specific reflex modification
      (CRM) as well as the number of beta amyloid-labeled neurons in the cortex and
      hippocampus were a function of the concentration of cholesterol in the diet. The
      data provide support for the idea that dietary cholesterol may facilitate
      learning and memory.

PMID- 17539482
TI  - Expression of endocannabinoid synthetic enzyme mRnas is correlated with
      cannabinoid 1 receptor mRNA in the mouse brain.
AB  - The two principal endocannabinoids, N-arachidonoyl-ethanolamine (anandamide) and
      2-arachidonoyl-glycerol (2-AG), are synthesized from arachidonic acid (AA) and AA
      is released as they are degraded. Therefore, the function of endocannabinoids is
      closely linked to AA, but the exact relationships have not been clarified,
      especially with respect to endocannabinoid metabolism. In the present study, oil
      rich in AA was administered (0, 100, 200 and 300 microl) orally to male mice for
      7 days. Phospholipase D (PLD), fatty acid amide hydrolase (FAAH), diacyl-glycerol
      lipase (DAGL), monoacyl-glycerol lipase (MAGL) and cannabinoid 1 (CB1) receptor
      mRNA expressions were determined in the whole brain. No changes in the expression
      of any gene investigated were detected following AA treatment. However, it was
      demonstrated that the expression of the CB1 receptor was positively correlated
      with PLD, FAAH and DAGL expression. This suggests that expression of the CB1
      receptor is closely coordinated with that of the enzymes which synthesize its
      ligands.

PMID- 17539483
TI  - Serum concentrations of antioxidant vitamins and carotenoids are low in
      individuals with a history of attempted suicide.
AB  - PRIMARY OBJECTIVE: Low consumption of fruits and vegetable has been reported in
      individuals with psychiatric disorders. We tested the hypothesis that antioxidant
      vitamins and carotenoids rich in fruits and vegetable may be consequently low
      among attempters. DESIGN AND METHODS: As a part of the Third National Health and
      Nutrition Examination Survey (NHANES III), 1988-1994, serum vitamins and
      carotenoids were measured in 6680 adults aged 17-39 years, who also completed a
      mental disorder diagnostic interview. Serum levels below gender-specific 1st
      quartile of the population were defined as low, otherwise as normal. RESULTS:
      Compared with non-attempters, prevalence ratios (PRs) of low alpha-carotene, beta
      cryptoxanthin in attempters were 1.45 (95% CI = 1.06-1.98) and 2.12 (1.47-3.08),
      respectively, the mean differences (nonattempter-attempter) of vitamin C,
      lutein/zeaxanthin and lycopene were 6.071 mmol/1 (SE = 1.948, p < 0.005), 0.041
      micromol/l (0.015, p < 0.005) and 0.045 micromol/l (0.015, p < 0.005)
      respectively. Total carotenoid was significantly lower (PR = 2.34 (1.56-3.49) and
      mean difference = 0.142 (0.058) micromol/l). These differences were reduced by
      adjustment for fruit/vegetables consumption, vitamin supplementation and serum
      cotinine, but remain significant for beta-cryptoxanthin, lycopene and total
      carotenoids. CONCLUSION: A history of attempted suicide is associated with low
      levels of antioxidant vitamins and carotenoids. Clinical importance of low
      antioxidants in attempters and interventional opportunity warrant further
      examination.

PMID- 17539484
TI  - Diverse physiological consequences of long-term sucrose consumption in female
      rats.
AB  - Although a considerable amount of work has addressed the short-term consequences
      of sucrose ingestion on a variety of morphological, physiological and
      hematological measures, relatively few studies have investigated these parameters
      following long-term sucrose intake. Results of the present experiments indicated
      that female rats given ad libitum access to a 10% sucrose solution for 9 months
      were conspicuously larger and had significantly heavier thyroid and spleen
      weights compared to rats offered either a restricted (20 min) daily sucrose
      option or control rats given only water. Rats given free access to sucrose also
      displayed abnormal serum levels of creatinine, sodium, phosphorus, alkaline
      phosphatase, alanine aminotransferase, uric acid and cholesterol which could
      indicate dysfunction in many organs including the kidney and liver. In the brain,
      however, chronic sucrose access was not associated with any discernable changes
      in neuronal or glial cell density within selected brain regions, but brain weight
      was found to be highly negatively correlated (r = - 0.97) with total sucrose
      intake. Finally, we report that high doses of estradiol can significantly
      attenuate the intake of sucrose in female rats. Together these findings
      demonstrate that free access to a sucrose solution for long periods can induce
      profound effects on rat physiology and may have important implications for the
      management of diet in humans.

PMID- 17539485
TI  - Postnatal dietary supplementation with either gangliosides or choline: effects on
      spatial short-term memory in artificially-reared rats.
AB  - This study addressed the hypothesis that dietary supplementation with either
      gangliosides or choline during the brain growth spurt would enhance short-term
      spatial memory. Male Long-Evans rats were reared artificially from postnatal days
      (PD) 5-18 and were fed diets containing either (i) choline chloride 1250 mg/l
      (CHL), (ii) choline chloride 250 mg/l and GD3 24 mg/l (GNG) or (iii) choline
      chloride 250 mg/l (STD). A fourth group (SCK) was reared normally. Rats were
      weaned onto AIN 93G diet and on PD 35 were trained on a cued delayed- matching-to
      place version of the Morris water maze. All groups learned to swim to the beacon
      that indicated the platform position on the first trial; similarly, on the second
      un-cued trial, the distance swam to reach the platform decreased to the same
      extent in all groups over the five days of training. The groups also responded in
      the same way to an increase in delay between the first and second trial from 1
      min to 1 h, showing an increase in the distance swam, accompanied by a decrease
      in the number of direct swims to the platform. Thus, all rats were equally
      proficient at using spatial short-term memory, regardless of the choline or
      ganglioside content of the preweaning diet.

PMID- 17539486
TI  - Protein restriction during lactation alters the autonomic nervous system control
      on glucose-induced insulin secretion in adult rats.
AB  - Involvement of autonomic nervous system (ANS) neurotransmitters on insulin
      secretion in rats submitted to protein malnutrition during lactation was studied.
      During the first 2/3 of lactation, mothers received a 4% protein diet (LP).
      Control group received normal diet (23% protein) (NP). After protein restriction,
      mothers received normal diets. At 81 days rats were submitted to intravenous
      glucose tolerance tests (ivGTT). Plasma glucose and insulin concentration (PIC)
      were measured. Glucose-induced insulin secretion (GIIS) was tested in pancreatic
      islets. Fasting normoglycemia and hypoinsulinemia were observed in LP rats.
      Glucose intolerance and low PIC in LP group were detected during ivGTT.
      Acetylcholine (Ach) or blockage of alpha-adrenoceptors induced high PIC increment
      in LP rats; atropine or stimulation of alpha-adrenoceptors did not change PIC.
      Insulin secretion of LP rat islets showed low glucose and carbachol responses.
      Epinephrine-inhibited GIIS in both islet groups. Hypoinsulinemia observed in
      lactation-malnourished rats might be caused by alterations in GIIS regulation,
      including ANS modulation.

PMID- 17539487
TI  - Iron regulation in C57BLI6 and DBA/2 mice subjected to iron overload.
AB  - Many genes are likely involved in the control of iron metabolism in brain and in
      peripheral tissues, and genetically-defined murine strains present the
      opportunity to investigate genetic variations in iron metabolism. Weanling
      C57BL/6 (B6) and DBA/2 (D2) mice were divided into two treatment groups receiving
      distilled water with or without 5000 ppm ferric chloride ad libitum as their sole
      fluid source for 100 days. Iron overload increased liver, spleen and plasma iron
      levels in male and female B6 and female D2 mice. In D2 males, liver iron was
      increased relative to control, but spleen and plasma iron remained unaffected.
      Brain iron content was not different between control and iron-treated mice in
      ventral midbrain, caudate, pons or hippocampus, but D2 iron overloaded mice
      displayed lower iron levels in nucleus accumbens and prefrontal cortex. We
      conclude that genetic background influences the accumulation of excess iron in
      the periphery and iron regulation in the central nervous system.

PMID- 17539488
TI  - Effects of intragastric administration of predigested nutrients on food intake,
      body weight and taste acceptability: potential relevance of the cephalic/neural
      phase of digestion.
AB  - In this study we analyzed the effect of the intragastric administration of
      partially digested and natural nutrients on subsequent food intake, body weight
      and flavor acceptability in rats. The results showed that enterally administered
      natural nutrients reduced the subsequent ingestion of food to a greater degree
      compared with the same nutrients in partially digested form. This greater
      reduction does not appear to be due to a higher nutritional effect of the former,
      because the body weight of both groups of animals was similar. Animals
      intragastrically administered with partially digested nutrients developed an
      acceptance response to a previously paired flavored stimulus, in contrast to
      animals receiving natural nutrients under the same conditions. These results are
      interpreted in terms of the cephalic phase of digestion and may be relevant to
      the treatment of clinical symptoms associated with enteral feeding.

PMID- 17539489
TI  - ECG of the month. Reversal of the arm leads or situs inversus with mirror-image
      dextrocardia? Reversal of the limb leads and of the precordial leads.

PMID- 17539490
TI  - Radiology case of the month. Knee pain and swelling in a man. Osteochondral
      defect.

PMID- 17539491
TI  - The Medical Education Commission report 2005 and 2006: Katrina kinetics change
      Graduate Medical Education.
AB  - The destructive and disruptive force of Hurricane Katrina was an enormous
      challenge to Graduate Medical Education (GME) in Louisiana. Before Katrina hit,
      GME was successful, prospering, steady, and productive in the state professional
      workforce, provision of clinical care, and economic development. That GME
      survived as well as it did, especially in the hardest hit institutions in New
      Orleans, is indeed remarkable, and greatly assisted by all other GME institutions
      in LA and across the U.S. As documented in this report, hits taken resulted in
      some loss and redistribution. The last two matches are compared, 2005 to 2006,
      and although both filled after the scramble, '06 is smaller. The year before
      Katrina (2004 to 2005) data on GME are included, and 2005 to 2006 will be posted
      when available. The approximate loss (16%) and redistribution scenarios are
      presented. National trends are also noted, as primary care specialties are less
      in the national match, even as a national response is begun to increase the short
      supply of physicians.

PMID- 17539492
TI  - Ochsner Health System Department of Anesthesiology: the first thirty years.
AB  - The Department of Anesthesiology at Ochsner Clinic Foundation was founded in 1947
      at the original Ochsner Hospital at Camp Plauche in New Orleans. An
      anesthesiology residency training program was accredited in 1953, making Ochsner
      one of the early and leading producers of anesthesiologists for the Gulf South
      region. Staff members over the years have held prominent national leadership
      positions, including two American Society of Anesthesiology presidents, the
      founder of the Society of Cardiovascular Anesthesiology, and the president of the
      Society for Obstetric Anesthesiology and Perinatology.

PMID- 17539493
TI  - Embolus-in-transit.
AB  - Embolus-in-transit leading to a paradoxical embolus or a pulmonary embolus is an
      uncommon phenomenon that requires a high degree of suspicion to make a clinical
      diagnosis. We present three interesting cases that have been encountered in our
      practice and describe the surgical treatment undertaken to correct the problem.

PMID- 17539494
TI  - An update on Salmonella in Louisiana.

PMID- 17539495
TI  - Coral reef canary.

PMID- 17539496
TI  - Mercury from underground estuary.

PMID- 17539497
TI  - Another toxin for the Baltic Sea?

PMID- 17539498
TI  - Scaling up microbial fuel cells.

PMID- 17539499
TI  - Taking out nitrates with a self-sufficient MFC.

PMID- 17539500
TI  - Models reveal pesticide exposure routes.

PMID- 17539501
TI  - High-efficiency solar cells come down to earth.

PMID- 17539502
TI  - The roles of State and Federal mobile-source emissions standards.

PMID- 17539503
TI  - Information flow and its significance in coherently integrated policymaking for
      promoting energy efficiency.
AB  - Why do negative, unexpected outcomes occur in sustainable development policies?
      What can we learn from them? Studies have shown clearly that, to be effective,
      sustainable development policies must be as coherent and integrated as possible;
      however, policy integration should not evolve into a tool that restricts
      creativity and undermines the relevance of local policy initiatives. The
      Coherently Integrated Policymaking frameworks, based on the precept that
      information flow is pivotal to the success of policymaking, are proposed and then
      applied to design an integrated energy efficiency policy that coaddresses a set
      of indicators. These indicators are energy and greenhouse gas reduction,
      improvement of public's health, increase in material efficiency, enhancementof
      energy equity, provision of employment and education opportunities, improvement
      of workers' health, improvement of local economy, and reduction in derived costs
      for the business community. Our framework also provides guidance for the
      magnitude of change a policy should introduce at one time, guided by five
      distinct types of feedback loops that link the different stakeholders involved in
      the design, implementation, and monitoring of integrated policies.

PMID- 17539504
TI  - Latitudinal gradient of airborne polyfluorinated alkyl substances in the marine
      atmosphere between Germany and South Africa (53 degrees N-33 degrees S).
AB  - Neutral, volatile polyfluorinated alkyl substances (PFAS) were determined in high
      volume air samples collected onboard the German research vessel Polarstern during
      cruise ANTXXIII-1 between Bremerhaven, Germany (53 degrees N) and Capetown,
      Republic of South Africa (33 degrees S) in fall 2005. An optimized and validated
      analytical protocol was used for the determination of several fluorotelomer
      alcohols (FTOHs) as well as N-alkylated fluorooctane sulfonamides and
      sulfonamidoethanols (FOSAs/FOSEs). Quantitative analyses were done by gas
      chromatography-mass spectrometry. This study provides the first concentration
      data of airborne PFAS from the Southern Hemisphere. Results indicate a strongly
      decreasing concentration gradient from the European continent toward less
      industrialized regions. The study confirms that airborne PFAS are mainly
      restricted to the Northern Hemisphere with a maximum concentration of 190 pg/m3
      (8:2 FTOH) in the first sample collected in the channel between the European
      mainland and the UK. However, south of the equator, trace amounts of several
      FTOHs and FOSAs with a maximum of 14 pg/m3 (8:2 FTOH) could still be detected.
      Furthermore, a selection of ionic PFAS including perfluorooctane sulfonate (PFOS)
      and perfluorooctanoate (PFOA) were determined in the particulate phase of high
      volume air samples by liquid chromatography-mass spectrometry. Levels of ionic
      PFAS were almost 2 orders of magnitude lower than those of neutral PFAS, with
      maximum concentrations in the first sample of 2.5 pg/m3 (PFOS) and 2.0 pg/m3
      (PFOA).

PMID- 17539505
TI  - Long-term fate of a pulse arsenic input to a eutrophic lake.
AB  - The long-term fate of a 30-year-old pulse arsenic input to a eutrophic lake was
      studied to determine if As has become effectively trapped in sediments or remains
      in active exchange with the water column. Legacy As was readily mobilized from
      sediments of Spy Pond (Arlington, MA), a eutrophic kettle-hole lake that was
      treated with 1000s kg As in the 1960s to manage excessive aquatic macrophyte
      growth. Arsenic was mobilized from hypolimnetic sediments during bottom-water
      anoxia in spring, summer, and fall, and As accumulated to maximum concentrations
      of 2100 nM. Mobilization of As from epilimnetic sediments was the largest source
      of As to the water column on a mass basis (145 mol), despite the fact that the
      epilimnion remains oxic year-round. Sediment cores revealed that surficial
      sediments contained As at 30-50 times background levels and suggested that there
      is contemporary As loading to hypolimnetic sediments (590 mol y(-1)). Mass
      balance estimates indicate that <5% of the contemporary As load comes from
      external inputs and that the remainder can be explained by mobilization and
      redistribution of legacy As, both through the water column and by vertical
      migration of dissolved As within sediments. These findings demonstrate that,
      decades after As inputs cease, As in contaminated sediments may remain labile and
      be mobilized to both anoxic and oxic water columns and accumulate to levels near
      the sediment surface and in the water column that may pose ongoing risks to
      ecological health.

PMID- 17539506
TI  - Brominated dibenzo-p-dioxins: a new class of marine toxins?
AB  - Levels of polybrominated dibenzo-p-dioxins (PBDDs) were measured in marine fish,
      mussels, and shellfish. PBDDs were nondetectable in samples from freshwater
      environments, and their levels were successively higher in samples from the
      marine environments of the Bothnian Bay and Bothnian Sea, the West Coast of
      Sweden, and the Baltic Proper. In Baltic Proper littoral fish the levels of PBDDs
      generally exceeded those of their chlorinated analogues (PCDDs). This is alarming
      as some Baltic fish species already are contaminated by chlorinated dioxins to
      such an extent that they cannot be sold on the European market. By comparing
      spatial trends in PBDD and PCDD distributions, and PBDD patterns in fish,
      mussels, and algae, we show that the PBDDs are probably produced naturally, and
      we propose a route for their biosynthesis. We further show that the levels of
      PBDDs are high (ng/g wet weight) in mussels, and that the levels increase over
      time. Finally, we discuss the possibility that the PBDDs have adverse biological
      effects, and that the levels are increasing as a result of global warming and
      eutrophication.

PMID- 17539507
TI  - Prestige oil spill. III. Fate of a heavy oil in the marine environment.
AB  - More than 200 oil samples were collected along the Northern Spanish coast, from
      December 2002 to December 2003, as part of the extensive monitoring program
      carried out by the Spanish Marine Safety Agency after the Prestige heavy oil
      spill (November 13, 2002). The GC FPD/ FID and comprehensive GC x GC/TOFMS sample
      profiles revealed the main characteristics of the oil residues. Chemical
      fingerprinting of the aliphatic and aromatic fractions by GC/ MS was performed to
      determine the source of the oil as well as to follow its weathering at sea. The
      (n-C13 + n-C14)/(n-C25 + n-C26), n-C18/phytane, and methylnaphthalene [(N +
      N1)/N2] ratios were found to be useful for assessing the evaporation,
      biodegradation, and dissolution processes, respectively. Other indicators of more
      advanced degradation processes, including photo-oxidation, were unaltered,
      showing the low incidence of natural weathering processes on the spilled heavy
      oil 1 year after the accident. The survey also demonstrated the occurrence of
      continued discharges of ballast waters at sea and the need for a more stringent
      surveillance of the area, beyond accidental oil spills.

PMID- 17539508
TI  - Lipid reserve dynamics and magnification of persistent organic pollutants in
      spawning sockeye salmon (Oncorhynchus nerka) from the Fraser River, British
      Columbia.
AB  - Pacific sockeye salmon (Oncorhynchus nerka) can travel several hundred kilometers
      to reach native spawning grounds and fulfill semelparous reproduction. The
      dramatic changes in lipid reserves during upstream migration can greatly affect
      internal toxicokinetics of persistent organic pollutants (POPs) such as PCBs,
      PCDDs, and PCDFs. We measured lipid content changes and contaminant
      concentrations in tissues (liver, muscle, roe/gonads) and biomarker responses
      (ethoxyresorufin O-deethylase or EROD activity and CYP1A levels) in two Pacific
      sockeye salmon stocks sampled at several locations along their spawning migration
      in the Fraser River, British Columbia. Muscle lipid contents declined
      significantly with increasing upstream migration distance and corresponded to
      elevated lipid normalized concentrations of PCBs and PCDD/Fs in spawning sockeye.
      Post-migration magnification factors (MFs) in spawning sockeye ranged between 3
      and 12 and were comparable to model-predicted MFs. sigmaPCBs(150-500 ng x g(-1)
      lipid), sigmaPCDD/Fs (1-1000 pg x g(-1) lipid) and 2,3,7,8-TCDD toxic equivalent
      or TEQ levels (0.1-15 pg x g(-1) lipid) in spawning sockeye were relatively low
      and did not affect hepatic EROD activity/CYP1A induction. Despite a 3-fold
      magnification, TEQ levels in eggs of spawning Fraser River sockeye did not exceed
      0.3 pg x g(-1) wet wt, a threshold level associated with 30% egg mortality in
      salmonids. PCBs in Fraser River sockeye are comparable to previous levels in
      Pacific sockeye. In contrast to Pacific sockeye from more remote coastal
      locations, PCDDs and PCDFs in Fraser River sockeye were generally minor
      components (<25%) of TEQ levels, compared to dioxin like PCB contributions
      (>75%). The data suggest that (i) the Fraser River is not a major contamination
      source of PCBs or PCDD/Fs and (ii) marine contaminant distribution, food-chain
      dynamics, and ocean-migration pathway are likely important factors controlling
      levels and patterns of POPs in returning Pacific sockeye. We estimate an annual
      chemical flux entering the Fraser River of up to 150 g for sigmaPCBs and 40 mg
      for sigmaPCDD/ Fs via returning sockeye. The results indicate that historical
      concentrations of PCBs and PCDD/Fs remain a potential threat to organism and
      ecosystem health on the west coast of Canada.

PMID- 17539509
TI  - Has submarine groundwater discharge been overlooked as a source of mercury to
      coastal waters?
AB  - We measured the mercury (Hg) in groundwater, aquifer sediments, and surface water
      in Waquoit Bay (Massachusetts) and found that this toxic metal (range: <3.2-262
      pM) was being released within the subterranean estuary, with similarly high
      levels (range: 18-256 pM) found in the surface waters of the bay. None of the
      dissolved species (DOC, chloride, and Fe) normally observed to influence Hg
      partitioning correlated well with the observed Hg concentrations. It was
      hypothesized that this was in part due to the variable loading in time and space
      of Hg onto the aquifer sands in combination with the seasonality of groundwater
      flow through the aquifer. Aquifer sediment samples from the study site ranged
      from <1 to 12.5 pmol of Hg/g of sediment, suggesting log Kd values on the order
      of 1. We hypothesize that this was due to the low organic carbon content typical
      of the aquifer sediments. Last, itwas estimated that submarine groundwater
      discharge supplied 0.47-1.9 nmol of Hg m(-2) day(-1) to the bay, which is an
      order of magnitude higher than the atmospheric deposition rate for the
      northeastern U.S.

PMID- 17539510
TI  - Composition of dioxin-like PCBs in fish: an application for risk assessment.
AB  - It is widely accepted that a congener-specific analysis of polychlorinated
      biphenyls (PCBs), rather than traditional Aroclor equivalent total PCB analysis,
      is required for risk assessment. This is based on the fact that environmental
      processes alter the original distribution of PCB congeners in Aroclors and that
      toxicity varies considerably among the congeners with dioxin-like PCBs (dl-PCBs)
      generally being among the most toxic. Using the largest known dl-PCB fish
      dataset, here we present a likely composition of dl-PCBs in fish. In contrast to
      common perception, we found that the dl-PCB composition is relatively constant
      (within approximately a factor of 2) regardless of fish species and total PCB
      level. The abundance of dl-PCBs expressed as a percentage of total PCB (25-75
      quartile range) in fish is generally in the order of PCB-118 (3.0-6.2%) > PCB-105
      (1.1-2.4%) > PCB-156 (0.39-0.75%) > PCB-167 (0.20-0.43%) > PCB-123 (0.11-0.26%) >
      PCB-157 (0.09-0.19%) = PCB-114 (0.08-0.18%) > PCB-189 (0.045-0.094%) > PCB-77
      (0.018-0.093%) > PCB-126 (0.015-0.036%) > PCB-81 (0.002-0.007%) = PCB-169 (0.001
      0.006%). The most toxic dl-PCB congeners PCB-126 and -169 contribute on average
      only 0.027 and 0.004% of total PCB, respectively. The statistically significant
      relationships presented between individual di-PCB and total-PCB concentrations
      can be used as a practical tool to estimate dl-PCBs for risk assessment purposes.
      A comparison of the dl-PCB pattern presented here with other studies suggests
      that this dl-PCB composition is applicable to fish from North America and perhaps
      from other geographical regions throughout the world.

PMID- 17539511
TI  - Diffusion of PAH in potato and carrot slices and application for a potato model.
AB  - A method for quantifying the effect of medium composition on the diffusive mass
      transfer of hydrophobic organic chemicals through thin layers was applied to
      plant tissue. The method employs two silicone disks, one serving as source and
      one as sink for a series of PAHs diffusing through thin layers of water, potato
      tissue, and carrot tissue. Naphthalene, phenanthrene, anthracene, and
      fluoranthene served as model substances. Their transfer from source to sink disk
      was measured by HPLC to determine a velocity rate constant proportional to the
      diffusive conductivity. The diffusive flux through the plant tissue was modeled
      using Fick's first law of diffusion. Both the experimental results and the model
      suggest that mass transfer through plant tissue occurs predominantly through pore
      water and that, therefore, the mass transfer ratio between plant tissue and water
      is independent of the hydrophobicity of the chemical. The findings of this study
      provide a convenient method to estimate the diffusion of nonvolatile organic
      chemicals through various plant materials. The application to a radial diffusion
      model suggests that "growth dilution" rendersthe concentration of highly
      hydrophobic chemicals in potatoes below their equilibrium partitioning level.
      This is in agreement with field results for the bioconcentration of PAHs in
      potatoes.

PMID- 17539512
TI  - Trophic dilution of polycyclic aromatic hydrocarbons (PAHs) in a marine food web
      from Bohai Bay, north China.
AB  - Trophic transfer of polycyclic aromatic hydrocarbons (PAHs) in aquatic ecosystems
      is an important criterion for assessing their ecological risk. This study
      analyzed 18 PAHs in phytoplankton/seston, zooplankton, five invertebrate species,
      five fish species, and one seabird species collected from Bohai Bay, and trophic
      transfer of the PAHs was determined in the food web, of which the length was
      approximately 4 on the basis of stable nitrogen isotope values. The
      concentrations of PAHs (2-64.5 ng/g wet weight) in the marine ecosystem were
      moderate compared with other marine organisms worldwide, and the PAH compositions
      exhibited species-specific profiles that were related to trophic levels in some
      organisms. Significant negative relationships were also found between trophic
      levels and lipid-normalized concentrations for 10 PAH compounds (acenaphthylene,
      anthracene, fluoranthene, pyrene, chrysene, benz[a]anthracene,
      benzo[b]fluoranthene + benzo[k]fluoranthene, benzo[e]pyrene, benzo[a]pyrene, and
      perylene), and their trophic magnification factors (TMFs) ranged from 0.11 for
      fluoranthene to 0.45 for acenaphthylene. These results confirm that PAHs undergo
      trophic dilution in the marine food web, which is likely to be the combined
      results of low assimilation efficiencies and efficient metabolic transformation
      at higher trophic levels.

PMID- 17539513
TI  - Aircraft measurement of organic aerosols over China.
AB  - Lower to middle (0.5-3.0 km altitude) tropospheric aerosols (PM2.5) collected by
      aircraft over inland and east coastal China were, for the first time,
      characterized for organic molecular compositions to understand anthropogenic,
      natural, and photochemical contribution to the air quality. n-Alkanes, fatty
      acids, sugars, polyacids are detected as major compound classes, whereas lignin
      and resin products, sterols, polycyclic aromatic hydrocarbons, and phthalic acids
      are minor species. Average concentrations of all the identified compounds
      excluding malic acid correspond to 40-50% of those reported on the ground sites.
      Relative abundances of secondary organic aerosol (SOA) components such as malic
      acid are much higher in the aircraft samples, suggesting an enhanced
      photochemical production over China. Organic carbon (OC) concentrations in summer
      (average, 24.3 microg m(-3)) were equivalent to those reported on the ground
      sites. Higher OC/EC (elemental carbon) ratios in the summer aircraft samples also
      support a significant production of SOA over China. High loadings of organic
      aerosols in the Chinese troposphere may be responsible to an intercontinental
      transport of the pollutants and potential impact on the regional and global
      climate changes.

PMID- 17539514
TI  - Daily and peak 1 h indoor air pollution and driving factors in a rural Chinese
      village.
AB  - We investigate wintertime indoor air quality and personal exposures to carbon
      monoxide (CO) in a rural village in Jilin province, where relatively homogeneous
      climatic and sociocultural factors facilitate investigation of household
      structural, fuel-related, and behavioral determinants of air pollution as well as
      relationships between different measures of air quality. Our time-resolved
      wintertime measurements of carbon monoxide and respirable particles (RSP) enable
      exploration of peak pollution periods in a village in Jilin Province, China,
      characterized by household use of both coal and biomass, as well as several
      "improved" (gas or electric) fuels. Our data indicate a 6-fold increase in peak 1
      h PM (1.9 mg/m3) concentrations relative to 24 h mean PM (0.31 mg/m3). Peak 1 h
      CO concentrations (20.5 ppm) routinely approached and often (27%) exceeded the
      World Health Organization's 1 h guideline of 26 ppm, although the vast majority
      (95%) of kitchens were within China's residential indoor air quality guideline
      for CO on a 24 h basis. Choice of heating fuel and household smoking status were
      significant predictors of indoor air quality. Whether solid or "improved" (gas or
      electric) fuel was used for cooking had an even stronger effect, but in the
      opposite direction from expected, on both peak and daily average measures of air
      pollution. Peak pollution period concentrations of CO and PM were strongly
      correlated to daily concentrations of CO and RSP, respectively. Our results
      suggestthat due to the primary role of heating as a determinant of wintertime
      indoor air quality in northern Chinese villages, health-oriented interventions
      limited to provision of improved cooking fuel are insufficient. Our results
      illustrate that peak pollution periods may routinely exceed exposure regulations
      and evacuation limits, although this and previous studies document typical 24 h
      CO concentrations in rural Chinese kitchens to be within guidelines. Within a
      given village and for a given pollutant, daily pollutant concentrations may be
      strong predictors of peak pollution period concentrations.

PMID- 17539515
TI  - Occurrence of 2,4-dichlorophenol and of 2,4-dichloro-6-nitrophenol in the Rhone
      River Delta (Southern France).
AB  - The compounds 2,4-dichlorophenol (2,4-DCP) and 2,4-dichloro-6-nitrophenol (6
      nitro-2,4-DCP) have been detected at microg L(-1) levels (10(-9)-10(-8) M) during
      the summer season 2005 in the water of the Rhone river delta. Compound 2,4-DCP
      would mainly derive from the transformation of the herbicide dichlorprop, heavily
      used in flooded rice farming (1400 kg in the delta region in 2005), in addition
      to being an impurity of the commercial herbicide. Field data show a fast
      concentration decrease of 2,4-DCP in the period June 21st to July 5th,
      accompanied by a corresponding increase of 6-nitro-2,4-DCP. This could imply a
      possible nitration process of 2,4-DCP into 6-nitro-2,4-DCP, with quite elevated
      yield (33%). Nitration of 2,4-DCP can be induced by photoproduced *NO2, the
      reaction kinetics (calculated in the presence of Fe(III) + nitrite under
      irradiation as model system) being d[6-nitro-2,4-DCP]/dt = 650 [2,4-DCP] [*NO2].
      Interestingly, the yield of the process (38%) is similar to that suggested by
      field data. An indirect assessment of [*NO2] in surface water in different sites
      of the Rhone delta indicated that 2,4-DCP could be transformed into 6-nitro-2,4
      DCP in a couple of weeks or less in the shallow water (10 cm depth) of the rice
      fields, a time scale that is compatible with field data. Photonitration of 2,4
      DCP is thus a possible process to account for the occurrence of 6-nitro-2,4-DCP
      in the Rhone delta.

PMID- 17539516
TI  - Chemical speciation and association of plutonium with bacteria, kaolinite clay,
      and their mixture.
AB  - We investigated the interactions of Pu(VI) with Bacillus subtilis, kaolinite
      clay, and a mixture of the two to determine and delineate the role of the
      microbes in regulating the environmental mobility of Pu. The bacteria, the
      kaolinite, and their mixture were exposed to a 4 x 10(-4) M Pu(VI) solution at pH
      5.0. The amount of Pu sorbed by B. subtilis increased with time, but had not
      reached equilibrium in 48 h, whereas equilibrium was attained in kaolinite within
      8 h. After 48 h, the oxidation state of Pu in the solutions exposed to B.
      subtilis and the mixture had changed to Pu-(V), whereas the oxidation state of Pu
      associated with B. subtilis and the mixture was Pu(IV). Exudates released from B.
      subtilis reduced Pu(VI) to Pu(V). In contrast, there was no change in the
      oxidation state of Pu in the solution or on kaolinite after exposure to Pu(VI).
      Scanning electron microscopy-energy dispersive spectrometry analysis indicated
      that most of the Pu in the mixture was associated with B. subtilis. These results
      suggest that Pu-(IV) is preferably sorbed to bacterial cells in the mixture and
      that Pu(VI) is reduced to Pu(V) and Pu(IV).

PMID- 17539517
TI  - Characterizing dissolved Cu and Cd uptake in terms of the biotic ligand and
      biodynamics using enriched stable isotopes.
AB  - The biotic ligand model considers the biological and geochemical complexities
      that affect metal exposure. It relates toxicity to the fraction of physiological
      active sites impacted by reactive metal species. The biodynamic model is a
      complementary construct that predicts bioaccumulation and assumes that toxicity
      occurs when influx rates exceed rates of loss and detoxification. In this paper
      we presume that metal influx rates are mechanistically the resulting processes
      that characterize transmembrane transport. We use enriched stable isotopes to
      characterize, both in terms of the biotic ligand and biodynamics, dissolved metal
      uptake by a freshwater snail at water hardness varying up to 180-fold. Upon 24 h
      exposure, metal uptake was linear over a range encompassing most environmental
      concentrations; although saturation kinetics were observed at higher
      concentrations. Cadmium influx rates correlate with changes in the affinity of
      the biotic ligand, whereas those of Cu correlate with changes in both site
      affinity and capacity. A relationship between metal influx rate and ligand
      character asks whether toxicity is the result of accumulation at the biotic
      ligand or the rate at which metal is transported by that ligand.

PMID- 17539518
TI  - Interactions between elevated CO2 and warming could amplify DOC exports from
      peatland catchments.
AB  - Peatlands export more dissolved organic carbon (DOC) than any other biome,
      contributing 20% of all terrestrial DOC exported to the oceans. Both warming and
      elevated atmospheric CO2 (eCO2) can increase DOC exports, but their interaction
      is poorly understood. Peat monoliths were, therefore, exposed to eCO2, warming
      and eCO2 + warming (combined). The combined treatment produced a synergistic
      (i.e., significant interaction) rise in DOC concentrations available for export
      (119% higher than the control, interaction P < 0.05) and enriched this pool with
      phenolic compounds (284%). We attribute this to increased plant inputs, coupled
      with impaired microbial degradation induced by competition with the vegetation
      for nutrients and inhibitory phenolics. Root biomass showed a synergistic
      increase (407% relative to the control, P < 0.1 only), while exudate inputs
      increased additively. Phenol oxidase was suppressed synergistically (58%,
      interaction P < 0.1 only) and beta-glucosidase (27%) additively, while microbial
      nutritional stress increased (51%) additively. Such results suggest intensified
      carbon exports from peatlands, with potentially widespread ramifications for
      aquatic processes in the receiving waters.

PMID- 17539519
TI  - Spectroscopic investigation of ciprofloxacin speciation at the goethite-water
      interface.
AB  - We investigated ciprofloxacin (a fluoroquinolone antibiotic) speciation as a
      function of pH in aqueous solution and in the presence of dissolved ferric ions
      and goethite using ATR-FTIR and UV-vis spectroscopy. The presence of dissolved
      and surface bound ferric species induced the deprotonation of the ciprofloxacin
      carboxylic acid group at pH < pKa1. The resultant ciprofloxacin zwitterions
      appeared to interact via both carboxylate oxygens to form bidentate chelate and
      bridging bidentate complexes within colloidal iron oxide-ciprofloxacin
      precipitates and bidentate chelates on the goethite surface. However, the
      structure of the aqueous ferric-ciprofloxacin complexes remains unclear. Our
      evidence for bidentate chelates (involving only the carboxylate oxygens) on the
      goethite surface was distinct from previous IR studies of fluoroquinolone
      sorption to metal oxides that have proposed surface complexes involving both the
      keto and the carboxylate groups. We find that the distinct ciprofloxacin surface
      complex proposed at the goethite-water interface may be a result of differences
      in metal oxide mineralogy or assignment of the carboxylate antisymmetric stretch
      in the metal oxide-fluoroquinolone spectra.

PMID- 17539520
TI  - Reactivity of ferric oxides toward H2S at low pH.
AB  - Goethite (gt), 2-line (21fh), 6-line ferrihydrite (61fh), and schwertmannite
      (shm) were reacted with H2S under steady-state conditions at pH 2.5-5 using a
      novel setup that consisted of an electrochemical sulfide generator transporting
      H2S into a suspension of oxides in a fluidized bed-reactor. The reactants were
      stoichiometrically converted into Fe2+ and So. Sulfate significantly inhibited
      the rates. Surface area normalized rates increased with pH. They depended on the
      mineral type following the order gt > 21fh > 61fh, contrasting previous
      observations at circumneutral pH with an inverse order. The rate of shm
      dissolution was highest probably due to direct reduction of dissolved ferric iron
      by H2S. A linear relationship between the observed rate and the surface species
      of H2S was derived from a surface complexation approach that allowed for the
      estimation of intrinsic rate constants kintr for the various oxides (38 min(-1),
      1.4 min(-1), 0.29 min(-1) for gt, 21fh, and 61fh, respectively). kint decreased
      with increasing deltaGf for the reactions and seems to depend on the reduction
      potential of the solution. From this observation we derived the hypothesis that
      kint is determined by the flat-band potential of the mineral/solute interface at
      low pH while being affected by surface interactions at higher pH.

PMID- 17539521
TI  - Phenanthrene sorption to soil humic acid and different humin fractions.
AB  - This study was undertaken to provide an insight into the effect of heterogeneous
      soil organic matter (SOM) on the sorption of phenanthrene. Humic acid (HA) and
      humin were extracted from a peat soil. Humin was further fractionated into bound
      humic acid (BHA), lipid, and insoluble residue (IR) fractions. Heterogeneous
      natures of these fractions were characterized by elemental analysis, ultraviolet
      visible spectroscopy, Fourier transform infrared spectroscopy, and solid-state
      13C NMR. Aliphaticity of the fractions followed the order lipid >BHA > HA > IR,
      while the polarity order was IR > BHA> HA > lipid. Sorption of phenanthrene on
      these fractions fitted the Freundlich equation, suggesting that phenanthrene
      sorption isotherms of lipid were almost linear (N = 0.993), while those of HA,
      BHA, and IR were nonlinear, with N values ranging from 0.723 to 0.910. The N
      values followed the order lipid > HA > BHA > IR and were significantly correlated
      inversely with their polarities (p < 0.05). Organic carbon-normalized sorption
      coefficients (K(FOC)) were independent of aliphatic or aromatic contents of the
      SOM fractions. The results suggested that SOM, especially for the humin
      fractions, was highly heterogeneous in terms of elemental composition, structure,
      and polarity. Such heterogeneity was considered to be responsible forthe
      nonlinear sorption of phenanthrene.

PMID- 17539522
TI  - Environmental factors influencing sorption of heterocyclic aromatic compounds to
      soil.
AB  - Heterocyclic organic compounds containing nitrogen, sulfur, or oxygen (NSOs) are
      an important class of groundwater contaminants related to the production and use
      of manufactured gas, heavy oils, and coal tar. Surprisingly little is known about
      the processes that control sorption and transport of NSOs in the subsurface. In
      this study, the effects of various environmental factors including temperature,
      ionic strength, and dissolved/sorbed ion composition on the sorption of NSOs have
      been investigated by means of a soil column chromatography approach. For the
      investigated compounds, increased temperature normally decreases their sorption
      to soil. The enthalpy change of the sorption process corroborates earlier
      findings that van der Waals forces dominate the sorption of S- and O-heterocyclic
      compounds such as thiophene, benzothiophene, benzofuran, and 2-methylbenzofuran.
      Ionic strength and ion composition (Ca2+ vs K+ at given ionic strength) of the
      aqueous phase show no significant effects on the sorption of these compounds.
      Previous studies demonstrated that for N-heterocyclic compounds, cation exchange
      and surface complex formation rather than partitioning into soil organic matter
      control their overall sorption. In contrast to S- and O-heterocyclic compounds,
      increasing ionic strength reduced the sorption of ionizable N-heterocyclic
      compounds (pyridine, 2-methylpyridine, quinoline, 2-methylquinoline, and
      isoquinoline), due to increased electrostatic competition by cations. At given
      ionic strength, an increase of the K+/Ca2+ ratio in the mobile phase enhanced the
      sorption of N-heterocyclic compounds, consistent with cation exchange of the
      protonated organic species as the dominating sorption process. Among the
      investigated N-heterocyclic compounds sorption of benzotriazole showed a peculiar
      feature in that ternary surface complexation with Ca2+ appears to be the dominant
      sorption mechanism.

PMID- 17539523
TI  - In situ measurements of metal complex exchange kinetics in freshwater.
AB  - Trace metals were measured in situ in a freshwater river draining a peat
      catchment (DOC = 15 mg L(-1)) using diffusive gradients in thin-films (DGT)
      devices with a range of gel layer thicknesses (0.16-2.0 mm). The reciprocal of
      the accumulated mass of each metal varied linearly with the thickness of the
      diffusive layer. These plots allowed calculation of the thickness of an apparent
      diffusive boundary layer (ADBL). A constant value was obtained from the plots of
      Cd, Pb, and Zn. The observed increase in the ADBL for the other metals
      (Mn<Co<Ni<Cu<AI<Fe) was consistent with increasing kinetic limitation of metal
      supplied from complexes with humic substances. The results could be presented as
      a kinetic signature, which reflects the nature of the binding ligands available
      in the water. A theoretical basis for deriving kinetic constants from the DGT
      measurements was developed. The derived association rate constants for Ni, Mn,
      and Cu were consistent with values calculated by assuming that the Eigen
      mechanism holds and that the mean stability constants of the complexes are
      related to the binding constants of each metal with fulvic acid. These first in
      situ measurements of dissociation rate constants provided larger values than
      those obtained by different techniques in the laboratory, suggesting that trace
      metal complexes in natural waters may be more labile than previously thought.

PMID- 17539524
TI  - Incorporation of Eu(III) into hydrotalcite: a TRLFS and EXAFS study.
AB  - The behavior of radionuclides in the environment (geo-, hydro-, and biosphere) is
      determined by interface reactions like adsorption, ion exchange, and
      incorporation processes. Presently, operational gross parameters for the
      distribution between solution and minerals are available. For predictive modeling
      of the radionuclide mobility in such systems, however, individual reactions and
      processes need to be localized, characterized, and quantified. A prerequisite for
      localization and clarification of the concerned processes is the use of modern
      advanced analytical and speciation methods, especially spectroscopy. In this
      study, Eu(III) was chosen as an analogue for trivalent actinides to identify the
      different species that occur by the Ln(III)/hydrotalcite interaction. Therefore,
      Eu(III) doped Mg-Al-Cl-hydrotalcite was synthesized and investigated by TRLFS,
      EXAFS, and XRD measurements. Two different Eu/hydrotalcite species were obtained.
      The minor part of the lanthanide is found to be inner-sphere sorbed onto the
      mineral surface, while the dominating Eu/hydrotalcite species consists of Eu(III)
      that is incorporated into the hydrotalcite lattice. Both Eu/hydrotalcite species
      have been characterized by their fluorescence emission spectra and lifetimes.
      Structural parameters of the incorporated Eu(III) species determined by EXAFS
      indicate a coordination number of 6.6 +/- 1.3 and distances of 2.41 +/- 0.02 A
      for the first Eu-OH shell.

PMID- 17539525
TI  - Nonlinear sorption of three alcohol ethoxylates to marine sediment: a combined
      Langmuir and linear sorption process?
AB  - Alcohol ethoxylates (AE) are nonionic surfactants mainly used in laundry cleaning
      products. The relation between particle bound and freely dissolved concentrations
      is an important entity in risk assessment. The mechanistic understanding of AE
      sorption is still poor, hampering extrapolations from laboratory studies to the
      field. We studied the sorption of three AE with 8 EO units but with increasing
      alkyl chains (C10, C12, and C14) to a marine sediment. Solid-phase
      microextraction, using polyacrylate as the extraction phase, was applied to
      measure freely dissolved concentrations in pore water. A model that combines a
      Langmuir and a linear sorption term fitted the nonlinear sorption data to
      sediment well. At low aqueous concentrations, adsorption dominates over
      absorption leading to higher distribution coefficients for AE at low field
      concentrations. This dual-mode model offers the possibility to extrapolate to
      other AE homologues and other marine sediments and also from high to low field
      concentrations.

PMID- 17539526
TI  - In situ colloid mobilization in Hanford sediments under unsaturated transient
      flow conditions: effect of irrigation pattern.
AB  - Colloid transport may facilitate off-site transport of radioactive wastes at the
      Hanford site, Washington State. In this study, column experiments were conducted
      to examine the effect of irrigation schedule on releases of in situ colloids from
      two Hanford sediments during saturated and unsaturated transientflow and its
      dependence on solution ionic strength, irrigation rate, and sediment texture.
      Results show that transient flow mobilized more colloids than steady-state flow.
      The number of short-term hydrological pulses was more important than total
      irrigation volume for increasing the amount of mobilized colloids. This effect
      increased with decreasing ionic strength. At an irrigation rate equal to 5% of
      the saturated hydraulic conductivity, a transient multipulse flow in 100 mM NaNO3
      was equivalent to a 50-fold reduction of ionic strength (from 100 mM to 2 mM)
      with a single-pulse flow in terms of their positive effects on colloid
      mobilization. Irrigation rate was more important for the initial release of
      colloids. In addition to water velocity, mechanical straining of colloids was
      partly responsible for the smaller colloid mobilization in the fine than in the
      coarse sands, although the fine sand contained much larger concentrations of
      colloids than the coarse sand.

PMID- 17539527
TI  - Superoxide mediated reduction of organically complexed iron(III): comparison of
      non-dissociative and dissociative reduction pathways.
AB  - We have investigated the mechanism of reduction of organically complexed
      iron(III) in the presence of superoxide, the one-electron reduced form of
      dioxygen that is produced in natural waters by thermal, photochemical, and
      biological pathways. Experimental results show that reduction of organically
      complexed iron(III) by superoxide may occur by either (or, in some instances,
      both) reaction of superoxide with inorganic iron(III) after its dissociation from
      the complex (dissociative reduction) or by direct reaction of superoxide with the
      complex (non-dissociative reduction). In the presence of low concentrations of
      ligands such as citrate and sulfosalicylate that bind iron(III) relatively weakly
      and result in complexes with high dissociation rate constants (kd > 1 x 10(-4) s(
      1)), a dissociative reduction pathway dominates. However, in the presence of
      strong ligands or high concentrations of weak ligands, only non-dissociative
      reduction of complexed iron(III) occurs. The relative contribution of each
      pathway has major implications for the lability and hence potential
      bioavailablity of iron in natural waters. The simple kinetic model developed here
      can be used to correctly predict the superoxide-mediated formation rates of
      iron(II) in natural systems.

PMID- 17539528
TI  - A case study of urban particle acidity and its influence on secondary organic
      aerosol.
AB  - Size-resolved indicators of aerosol acidity, including H+ ion concentrations
      (H+Aer) and the ratio of stoichiometric neutralization are evaluated in
      submicrometer aerosols using highly time-resolved aerosol mass spectrometer (AMS)
      data from Pittsburgh. The pH and ionic strength within the aqueous particle phase
      are also estimated using the Aerosol Inorganics Model (AIM). Different mechanisms
      that contribute to the presence of acidic particles in Pittsburgh are discussed.
      The largest H+Aer loadings and lowest levels of stoichiometric neutralization
      were detected when PM1 loadings were high and dominated by SO4(2-). The average
      size distribution of H+Aer loading shows an accumulation mode at Dva
      approximately 600 nm and an enhanced smaller mode that centers at Dva
      approximately 200 nm and tails into smaller sizes. The acidity in the
      accumulation mode particles suggests that there is generally not enough gas-phase
      NH3 available on a regional scale to completely neutralize sulfate in Pittsburgh.
      The lack of stoichiometric neutralization in the 200 nm mode particles is likely
      caused by the relatively slow mixing of gas-phase NH3 into SO2-rich plumes
      containing younger particles. We examined the influence of particle acidity on
      secondary organic aerosol (SOA) formation by comparing the mass concentrations
      and size distributions of oxygenated organic aerosol (00A--surrogate for SOA in
      Pittsburgh) during periods when particles are, on average, acidic to those when
      particles are bulk neutralized. The average mass concentration of ODA during the
      acidic periods (3.1 +/- 1.7 microg m(-3)) is higher than that during the
      neutralized periods (2.5 +/- 1.3 microg m(-3)). Possible reasons for this
      enhancement include increased condensation of SOA species, acid-catalyzed SOA
      formation, and/or differences in air mass transport and history. However, even if
      the entire enhancement (approximately 0.6 microg m(-3)) can be attributed to acid
      catalysis, the upperbound increase of SOA mass in acidic particles is
      approximately 25%, an enhancement that is much more moderate than the multifold
      increases in SOA mass observed during some lab studies and inferred in SO2-rich
      industrial plumes. In addition, the mass spectra of OOA from these two periods
      are almost identical with no discernible increase in relative signal intensity at
      larger m/z's (>200 amu), suggesting that the chemical nature of SOA is similar
      during acidic and neutralized periods and that there is no significant
      enhancement of SOA oligomer formation during acidic particle periods in
      Pittsburgh.

PMID- 17539529
TI  - Relative reactivity of amino acids with chlorine in mixtures.
AB  - The relative reactivity of chlorine with amino acids is an important determinant
      of the resulting chlorination products in systems where chlorine is the limiting
      reagent, for example, in the human gastrointestinal tract after consumption of
      chlorine-containing water, or during food preparation with chlorinated water.
      Since few direct determinations of the initial reactivity of chlorine with amino
      acids have been made, 17 amino acids were compared in this study using
      competitive kinetic principles. The experimental results showed that (1) most
      amino acids have similar initial reactivities at neutral pH; (2) amino acids with
      thiol groups such as methionine and cysteine are exceptionally reactive and
      produce sulfoxides; (3) amino acids without thiol groups primarily undergo
      monochlorination of the amino nitrogen; and (4) glycine and proline are the least
      reactive. Dichlorination was estimated to occur with approximately 26% of the
      amino acid groups when the total amino acid: chlorine concentrations were equal.

PMID- 17539530
TI  - Modeling energy use and emissions from North American shipping: application of
      the ship traffic, energy, and environment model.
AB  - The waterway network ship traffic, energy, and environment model (STEEM) is
      applied to geographically characterize energy use and emissions for interport
      ship movement for North America, including the United States, Canada, and Mexico.
      STEEM advances existing approaches by (i) estimating emissions for large regions
      on the basis of nearly complete data describing historical ship movements,
      attributes, and operating profiles of individual ships, (ii) solving distances on
      an empirical waterway network for each pair of ports considering ship draft and
      width constraints, and (iii) allocating emissions on the basis of the most
      probable routes. We estimate that the 172 000 ship voyages to and from North
      American ports in 2002 consumed about 47 million metric tonnes of heavy fuel oil
      and emitted about 2.4 million metric tonnes of SO2. Comparison with port and
      regional studies shows good agreement in total estimates and better spatial
      precision than current top-down methods. In quantifying limitations of top-down
      approaches that assume existing proxies for ship traffic density are spatially
      representative across larger domains, we find that International Comprehensive
      Ocean-Atmosphere Data Set (ICOADS) proxy data are spatially biased, especially at
      small scales. Emissions estimated by STEEM for ships within 200 nautical miles of
      the coastal areas of the United States are about 5 times the emissions estimated
      in previous studies using cargo as a proxy.

PMID- 17539531
TI  - Merging models and biomonitoring data to characterize sources and pathways of
      human exposure to organophosphorus pesticides in the Salinas Valley of
      California.
AB  - We characterize cumulative intakes of organophosphorus (OP) pesticides in an
      agricultural region of California by drawing on human biomonitoring data,
      California pesticide use reporting (PUR) data, and limited environmental samples
      together with outputs from the CalTOX multimedia, multipathway, source-to-dose
      model. The study population is the CHAMACOS cohort of almost 600 pregnant Latina
      women in the Salinas Valley region. We use model estimates of OP intake and
      urinary dialkylphosphate (DAP) metabolite excretion to develop premises about
      relative contributions from different exposure sources and pathways. We evaluate
      these premises by comparing the magnitude and variation of DAPs in the CHAMACOS
      cohort with those of the whole U.S. population using data from the National
      Health and Nutrition Examination Survey (NHANES). This comparison supports the
      premise that diet is the common and dominant exposure pathway in both
      populations. Biomarker comparisons and model results support the observation
      that, relative to NHANES, the CHAMACOS population has a statistically significant
      (p < 0.001) added intake of OP pesticides with low inter-individual variability.
      We attribute the magnitude and small variance of this intake to residential
      nondietary exposures from local agricultural OP uses. These results show that
      mass-balance models can estimate exposures for OP pesticides within the range
      measured by biological monitoring.

PMID- 17539532
TI  - Indoor vapor intrusion with oxygen-limited biodegradation for a subsurface
      gasoline source.
AB  - Development and results are presented for a subsurface soil to indoor air
      chemical vapor intrusion model that includes oxygen-limited biodegradation. The
      algebraic model incorporates a steady-state subsurface gasoline vapor source,
      diffusion-dominated soil vapor transport in a homogeneous subsurface soil layer,
      and mixing within a building enclosure. The soil is divided into a shallow
      aerobic layer including biodegradation and a deeper anaerobic layer in which
      biodegradation is neglected. Biodegradation of multiple chemicals is included,
      with aerobic first-order reaction kinetics estimated from measured data. Oxygen
      is supplied at the soil surface below the building foundation. Oxygen demand is
      attributed to a sum of multiple biodegrading chemicals and to baseline
      respiration of native soil organic matter. The model is solved by iteratively
      varying the aerobic depth to match oxygen demand to oxygen supply. Model results
      are calculated for ranges of source concentrations, unsaturated soil
      characteristics, and building parameters. Results indicate vapor intrusion of
      petroleum hydrocarbons can be significantly less than indicated by estimates that
      neglect biodegradation.

PMID- 17539533
TI  - The origin and significance of short-term variability of semivolatile
      contaminants in air.
AB  - Persistent semivolatile contaminants such as polychlorinated biphenyls (PCBs)
      cycle between air and surface media in the environment. At different locations
      and times, PCB concentrations in air over a diel (24-hour) period have been
      observed to have maxima either during the day or at night. These observations
      have been interpreted as evidence of temperature-mediated air-surface exchange
      and of degrading reactions with hydroxyl radicals in the atmosphere. However, a
      general explanation of the processes responsible for the observed diel
      variability in concentrations has not been provided. Here, we interpret diel
      monitoring data using a multimedia mass balance model parametrized with local
      data on temperature, wind speed, atmospheric mixing height, and hydroxyl radical
      concentrations. We demonstrate that four factors are sufficient to account for
      the variability of PCB concentrations in air over a diel period; temperature,
      local atmospheric stability, hydroxyl radical concentration, and source type. We
      apply the model to re-interpret past diel monitoring studies and find that the
      observed patterns of concentrations can be rationalized by consideration of these
      factors. Using insights from this study, future diel monitoring campaigns can be
      targeted to observe the influence of specific fate and transport processes. Such
      studies will contribute to more accurate understanding of the processes
      controlling the short-term local, and long-term global fate of persistent
      semivolatile contaminants.

PMID- 17539534
TI  - Modeling sorption of anionic surfactants onto sediment materials: an a priori
      approach for perfluoroalkyl surfactants and linear alkylbenzene sulfonates.
AB  - A mechanistically derived model predicting the sorption of anionic surfactants to
      sediments was developed and evaluated for three classes of surfactants:
      perfluoroalkyl carboxylates, perfluoroalkyl sulfonates, and linear alkylbenzene
      sulfonates. The model includes both hydrophobic and electrostatic components and
      estimates the contribution of each to the sediment-water distribution coefficient
      (Kd) using Gibbs free energy terms. The hydrophobic free energy term was
      calculated from the aqueous solubilities of non-charged alkylbenzene or
      perfluoroalkane analogs and prior observations of increases in Kd values with
      increasing chain lengths. The electrostatic term was calculated from aqueous
      solution measurements using the non-ideal competitive adsorption Donnan (NICA
      Donnan) model. The NICA-Donnan calculations were performed using parameters
      previously derived for generic humic acids. These two terms were coupled by
      multiplying by the fraction of organic carbon in the sediment, foc, and a single
      fitting parameter, Faccess, the volumetric fraction of organic carbon accessible
      to the sorbing surfactant. The combined model accurately predicted the sediment
      water distribution coefficients for all three classes of anionic surfactants. In
      its current formulation, the model was unable to capture the slight degree of
      isotherm nonlinearity observed for these surfactants.

PMID- 17539535
TI  - Transport of methane and noble gases during gas push-pull tests in dry porous
      media.
AB  - A field method called the gas push-pull test (GPPT) was previously developed and
      tested for the in situ quantification of aerobic methane (CH4) oxidation by soil
      microorganisms. The GPPT consists of an injection followed by extraction of
      reactant and tracer gases into and out of the soil. Quantification of microbial
      activities from GPPTs requires insight in the transport of reactant and tracer
      gases under diverse field conditions. We investigated how the transport of
      differenttracer gases (He, Ne, and Ar) compares to that of the reactant gas CH4
      during GPPTs conducted in a well-defined, dry porous media that mimicked an open
      system. Transport of gaseous components during GPPT is mainly driven by advection
      resulting from injection and extraction and diffusion driven by concentration
      gradients. Regardless of the advective component (selected injection/ extraction,
      flow rates 0.2-0.8 L min(-1)), diffusion was the dominant transport mechanism for
      gaseous components. This resulted in dissimilar transport of CH4 and the tracers
      He and Ne. Numerical simulations of GPPTs showed that similar transport of these
      components is only achieved at very high injection/extraction rates that, in
      practice, are not feasible since they would imply extremely short duration times
      of GPPTs to allow for consumption of a measurable amount of reactant(s) by soil
      microorganisms. However, Ar transport was similar to that of CH4. Hence, Ar may
      be a good tracer provided that it is injected at high concentrations (e.g., >25%
      [v/v]) to overcome its background concentration in soil air. Using moderate
      injection/ extraction rates (e.g., 0.6 L min(-1)) with injected volumes of 10-30
      L will result in GPPT durations of 1-3 h, which would suffice to attain a
      measurable consumption of reactant(s) in soils having relatively high (e.g.,
      first-order rate constants >0.3 h(-1)) microbial activities.

PMID- 17539536
TI  - Determination of xenobiotic intrinsic clearance in freshly isolated hepatocytes
      from rainbow trout (Oncorhynchus mykiss) and rat and its application in
      bioaccumulation assessment.
AB  - Bioaccumulation in fish depends on the dynamics of various processes that involve
      fish uptake, storage, and elimination of xenobiotics. Elimination via fish
      biotransformation is a primary process that can be evaluated in an in vitro
      system to improve the performance of the prediction of xenobiotic bioaccumulation
      potentials. In this study, values of intrinsic clearance (CLint) of seven
      reference compounds (atrazine, molinate, 4,4-bis(dimethylamino)-benzophenone, 4
      nonylphenol, 2,4-di-tert-butylphenol, trifluralin, benzo(a)pyrene) in hepatocytes
      freshly isolated from rainbow trout and rat were determined using a substrate
      depletion approach. Atrazine was metabolized in rat hepatocytes with a CLint
      value of 3.81 +/- 1.96 mL/h/ 10(6) cells, whereas in trout hepatocytes, the
      clearance was not significant until very high cell concentration was used and the
      rate was estimated to be approximately 0.002 mL/h/10(6) cells. Intrinsic
      clearance values for all other compounds were 5.5-78.5-fold lower in trout
      hepatocytes than those in rat hepatocytes. Trout hepatic clearance (CL(H)) values
      were extrapolated from the CLint values using a "well-stirred" liver model.
      Biotransformation rate constants (kMET) of the compounds in trout were
      subsequently estimated and used as inputs to a kinetic model for the prediction
      of bioconcentration factors (BCF) in fish. Compared to the BCF values predicted
      without consideration of fish biotransformation, the inclusion of estimated kMET
      values significantly improved fish BCF predictions for the reference compounds.
      This study demonstrates a framework for future bioaccumulation assessment of
      xenobiotics using combined information of the physical-chemical properties of the
      compounds and the biotransformation potentials of the compounds in fish.

PMID- 17539537
TI  - Mitochondrial multiplex real-time PCR as a source tracking method in fecal
      contaminated effluents.
AB  - Multiplex real-time PCR amplifying fecal mitochondrial DNA (mtDNA) combined with
      rapid, crude DNA preparations are promising additions to surface water source
      tracking methods. Amplification of eukaryotic mitochondrial DNA identifies the
      fecal source directly and can be used in conjunction with other intestinal
      microbial methods to characterize effluents. Species-specific primers and dual
      labeled probes for human, swine, and bovine NADH dehydrogenase subunit 5 (ND5)
      genes were created for multiplex real-time PCR in feces and effluent slurries.
      The linear range of the multiplex assay was 10(2)-10(7) mtDNA copies for human,
      bovine, and swine effluent in combination (equal volumes). PCR amplification
      efficiencies for bovine, human, and swine mtDNA when assayed in combination were
      93, 107, and 92% respectively. Linear regression correlation coefficients (r2)
      were 0.99 for all standard curves except for human mtDNA in combination (r2 =
      0.95). Multiplex amplification of bovine, human, and swine mtDNA (ND5) exhibited
      no cross-reactions between the effluents from three species of interest. Also, no
      cross-reactions were observed with effluents of other vertebrates: sheep, goat,
      horse, dog, cat, Canada goose, broiler, layer, turkey, and tilapia. Performed as
      a blind test, the PCR operator was able to correctly identify all but two
      effluent challenge samples (10/12 or 83% correct) with no false positives (22/22
      or 100% correct). The multiplex assay had a tendency to detect the species of
      highest mtDNA concentration only. Better detection of all three species in a
      combination of human, bovine, and swine effluents was accomplished by running
      each real-time PCR primer/ probe set singly. Real-time PCR detection limit was
      calculated as 2.0 x 10(6) mitochondrial copies or 0.2 g of human feces per 100 mL
      effluent. Some carry-over mtDNA PCR signal from consumed beef, but not pork, was
      found in feces of human volunteers.

PMID- 17539538
TI  - Selenium and arsenic speciation in fly ash from full-scale coal-burning utility
      plants.
AB  - X-ray absorption fine structure spectroscopy has been used to determine directly
      the oxidation states and speciation of selenium and arsenic in 10 fly ash samples
      collected from full-scale utility plants. Such information is needed to assess
      the health risk posed by these elements in fly ash and to understand their
      behavior during combustion and in fly ash disposal options, such as sequestration
      in tailings ponds. Selenium is found predominantly as Se(IV) in selenite (SeO3(2
      )) species, whereas arsenic is found predominantly as As(V) in arsenate (AsO4(3
      )) species. Two distinct types of selenite and arsenate spectra were observed
      depending upon whether the fly ash was derived from eastern U.S. bituminous (Fe
      rich) coals or from western subbituminous or lignite (Ca-rich) coals. Similar
      spectral details were observed for both arsenic and selenium in the two different
      types of fly ash, suggesting that the postcombustion behavior and capture of both
      of these elements are likely controlled by the same dominant element or phase in
      each type of fly ash.

PMID- 17539539
TI  - RBS characterization of arsenic(III) partitioning from aqueous phase into the
      active layers of thin-film composite NF/RO membranes.
AB  - The main objective of this study was to apply Rutherford backscattering
      spectrometry (RBS) for characterizing the partitioning of arsenic(III) from
      aqueous phase into the active layer of NF/RO membranes. NF/RO membranes with
      active layer materials including polyamide (PA), PA-polyvinyl alcohol derivative
      (PVA), and sulfonated-polyethersulfone (SPES) were investigated. The partition
      coefficient was found to be constant in the investigated As-(III) concentration
      range of 0.005-0.02 M at each pH investigated. The partitioning of As(III) when
      predominantly present as H3AsO3 (pH 3.5-8.0) was not affected by pH. In contrast,
      the partition coefficient of As(III) at pH 10.5, when it was predominantly
      present as H2AsO3-, was found to be approximately 33-49% lower than that of
      H3AsO3. The partition coefficients of H3AsO3 and H2AsO3- for membranes containing
      PA in their active layers were within the respective ranges of 6.2-8.1 and 3.6
      5.4, while the corresponding values (4.8 and 3.0, respectively) for the membrane
      with SPES active layer were approximately 30% lower than the average values for
      the PA membranes.

PMID- 17539540
TI  - Phosphorus removal mechanisms in active slag filters treating waste stabilization
      pond effluent.
AB  - Phosphorus (P) removal mechanisms from waste stabilization pond effluent by a
      melter slag filter were investigated. The studied filter had treated pond
      effluent for a decade, but lost its P removal efficiency after 5 years. The P
      distribution in the slag was examined by scanning electron microscopy (SEM),
      electron dispersive spectrometry (EDS), X-ray fluorescence (XRF), X-ray
      diffraction (XRD), and chemical fractionation. The results showed the slag to be
      covered by a film comprising metal oxides/oxyhydroxides, organic resin, and Fe
      phosphate precipitates. The slag porous matrix beneath this film hosted lower P
      concentrations and consisted of metal oxides/oxyhydroxides and calcmagnesium
      silicates. The study revealed the following mechanisms for P removal from
      effluent by the melter slag: (1) P adsorption onto metal oxides/oxyhydroxides
      which are ubiquitous throughout the porous slag matrix and its surface film; (2)
      P precipitation, mainly as Fe-phosphates (determined by SEM/EDS) on the surface
      film, derived from the release of metal ions into the solution phase; and (3) P
      sequestration by an amorphous organic resin that comprises a substantial
      proportion of the surface film, which was deduced by SEM/EDS and XRF. Results of
      chemical extractions performed on the slag demonstrated that 1 M HCl, which has
      been used to determine Ca-associated P in previous studies, is an unreliable Ca-P
      marker. By contrast, the citrate-dithionite reagent was shown to be a good
      indicator of Fe/Al-associated P and revealed that adsorption onto metal
      oxides/oxyhydroxides, in the porous matrix as well as its surface film, is the
      most significant P removal mechanism achieved by the slag filter.

PMID- 17539541
TI  - Reduction of point contamination sources of pesticide from a vineyard farm.
AB  - Although plant protection products are already regulated in Europe under
      Directive 91/414/EEC, there is increasing concern about the pollution of ground
      and surface water caused by point sources of pesticides, such as tank filling,
      spillages, faulty equipment, washing, waste disposal, and direct contamination.
      One tool for the reduction of pesticide point source contamination is a
      biological system where chemicals are bound and biologically degraded. This paper
      presents an offset lined system where wastewaters containing pesticide residues
      leach through a biomix. A pump system is provided to pump the water onto the
      surface of the biomix and allow it to drain under gravity, keeping the biomix
      wet. The analysis of residues of nine pesticides in the water, biomix, and
      sediment inside the tank showed the biobed to function well, with a water
      decontamination greater than 90%. The use of this system mitigated the potential
      for pollution (pesticide concentrations higher than 0.1 microg/L) of 1 km of the
      river system surrounding the farm.

PMID- 17539542
TI  - Characterization of disinfection byproduct precursors based on hydrophobicity and
      molecular size.
AB  - Natural organic matter (NOM) from five water sources was fractionated using XAD
      resins and ultrafiltration membranes into different groups based on
      hydrophobicity and molecular weight (MW), respectively. The disinfection
      byproduct formation from each fraction during chlorination and chloramination was
      studied. In tests using chlorination, hydrophobic and high MW (e.g., >0.5 kDa)
      precursors produced more unknown total organic halogen (UTOX) than corresponding
      hydrophilic and low MW (e.g., <0.5 kDa) precursors. Trihaloacetic acid (THAA)
      precursors were more hydrophobic than trihalomethane (THM) precursors. The
      formation of THM and THAA was similar among different fractions for a water with
      low humic content. Hydrophilic and low MW (<0.5 kDa) NOM fractions gave the
      highest dihaloacetic acid (DHAA) yields. No significant difference was found for
      DHAA formation among different NOM fractions during chloramination. Increasing pH
      from 6 to 9 led to lower TOX formation for hydrophobic and high MW NOM fractions
      but had little impact on TOX yields from hydrophilic and low MW fractions.
      Bromine and iodine were more reactive with hydrophilic and low MW precursors as
      measured by THM or HAA formation than their corresponding hydrophobic and high MW
      precursors. However, hydrophobic and high MW precursors produced more UTOX when
      reacting with bromine and iodine.

PMID- 17539543
TI  - The primary aerobic biodegradation of gasoline hydrocarbons.
AB  - We describe the primary aerobic biodegradation of an unleaded, unoxygenated,
      regular gasoline by inocula from unacclimated fresh and sea water, and from a
      domestic sewage treatment plant. Biodegradation was rapid and complete in all
      inocula, with an overall median "half-life", at approximately 70 ppm gasoline and
      low levels of inorganic nutrients, of 5 days. The biodegradation of 131
      individual hydrocarbons in the gasoline followed a relatively consistent pattern.
      The larger n-alkanes and iso-alkanes, and simple and alkylated aromatic compounds
      were the most readily degraded compounds, followed by the smaller n-alkanes and
      isoalkanes and the naphthenes. The last compounds to be degraded were butane, iso
      butane, and 2,2-dimethylbutane, but even these disappeared with an apparent half
      life of <30 days. The fact that the aqueous concentration of many of the
      individual components was in the sub ppb level is a remarkable demonstration of
      the ability of unadapted indigenous aerobic microorganisms to respond to and
      effectively biodegrade gasoline range hydrocarbons.

PMID- 17539544
TI  - Hydrous ferric oxide incorporated diatomite for remediation of arsenic
      contaminated groundwater.
AB  - Two reactive media [zerovalent iron (ZVI, Fisher Fe0) and amorphous hydrous
      ferric oxide (HFO)-incorporated porous, naturally occurring aluminum silicate
      diatomite [designated as Fe (25%)-diatomite]], were tested for batch kinetic, pH
      controlled differential column batch reactors (DCBRs), in small- and large-scale
      column tests (about 50 and 900 mL of bed volume) with groundwater from a
      hazardous waste site containing high concentrations of arsenic (both organic and
      inorganic species), as well as other toxic or carcinogenic volatile and
      semivolatile organic compounds (VOC/SVOCs). Granular activated carbon (GAC) was
      also included as a reactive media since a permeable reactive barrier (PRB) at the
      subject site would need to address the hazardous VOC/SVOC contamination as well
      as arsenic. The groundwater contained an extremely high arsenic concentration
      (341 mg L(-1)) and the results of ion chromatography and inductively coupled
      plasma mass spectrometry (IC-ICP-MS) analysis showed that the dominant arsenic
      species were arsenite (45.1%) and monomethyl arsenic acid (MMAA, 22.7%), while
      dimethyl arsenic acid (DMAA) and arsenate were only 2.4 and 1.3%, respectively.
      Based on these proportions of arsenic species and the initial As-to-Fe molar
      ratio (0.15 molAs mole(-1)), batch kinetic tests revealed that the sorption
      density (0.076 molAs molFe(-1)) for Fe (25%)-diatomite seems to be less than the
      expected value (0.086 molAs molFe(-1) calculated from the sorption density data
      reported by Lafferty and Loeppert (Environ. Sci. Technol. 2005, 39, 2120-2127),
      implying that natural organic matters (NOMs) might play a significant role in
      reducing arsenic removal efficiency. The results of pH-controlled DCBR tests
      using different synthetic species of arsenic solution showed that the humic acid
      inhibited the MMAA removal of Fe (25%)-diatomite more than arsenite. The mixed
      system of GAC and Fe (25%)-diatomite increased the arsenic sorption speed to more
      than that of either individual media alone. This increase might be deduced by the
      fact that the addition of GAC could enhance arsenic removal performance of Fe
      (25%)-diatomite through removing comparably high portions of NOMs. Small- and
      large-scale column studies demonstrated that the empty bed contact time (EBCT)
      significantly affected sorpton capacities at breakthrough (C = 0.5 C0) forthe
      Fe0/sand (50/50, w/w) mixture, but notfor GAC preloaded Fe (25%)-diatomite. In
      the large-scale column tests with actual groundwater conditions, the GAC
      preloaded Fe (25%)-diatomite effectively reduced arsenic to below 50 microg L(-1)
      for 44 days; additionally, most species of VOC/SVOCs were also simultaneously
      attenuated to levels below detection.

PMID- 17539545
TI  - Efficient approach for Cd2+ and Ni2+ removal and recovery using mesoporous
      adsorbent with tunable selectivity.
AB  - Cadmium pollution from the manufacture and disposal of NiCd batteries remains an
      important problem in developing countries. Among the available remedial
      technologies, adsorption is popular because of its low cost and simplicity. The
      mesoporous NH2-MCM-41 displays good adsorption capacities for cadmium and nickel
      ions. This work demonstrated for the first time the use of the competition
      between complexant and sorbentto create high adsorption selectivity. The
      selectivity was manipulated by the judicious use of a chelating agent, thus
      achieving on-demand 100% selectivity for either Cd2+ or Ni2+ adsorption. Single
      and binary components adsorption studies, carried out with different metals and
      EDTA concentrations, solution compositions and pH, showed that NH2-MCM-41 adsorbs
      only cadmium with a capacity of 0.56 mmol g(-1) from binary mixtures at
      [EDTA]/[M2+] = 0.5 and pH 5. The NH2-MCM-41 displays 100% selectivityfor nickel
      adsorption at [EDTA]/[M2+] = 0.5 and pH 2 with a measured adsorption capacity of
      0.50 mmol g(-1). Pure Cd2+ and Ni2+ solutions were recovered by a simple acid
      wash, and the regenerated adsorbent could be reused without lost of performance
      (i.e., adsorption capacity and selectivity).

PMID- 17539546
TI  - Oxidation on zerovalent iron promoted by polyoxometalate as an electron shuttle.
AB  - Most studies on zerovalent iron (ZVI) were mainly focused on the reductive
      transformation of halo- or nitrocompounds. Oxidation reactions occurring on ZVI
      have been recently recognized. In this study, we demonstrate that the oxidation
      pathways on ZVI can be accelerated by the presence of polyoxometalate (POM:
      nanosized metaloxygen cluster anion) serving as an electron shuttle. The ions,
      SiW12O40(4-) and PW12O40(3-), can mediate the electron transfer from the Fe0
      surface to 02 while enhancing the production of H2O2, which subsequently
      initiates the OH radical-mediated oxidation through a Fenton-type reaction. The
      oxidation reaction was completely quenched by adding methanol as an OH radical
      scavenger. On the other hand, PMo12O40(3-) completely inhibited the oxidative
      degradation by irreversibly scavenging an electron and holding it. We
      systematically investigated the effects of iron loading, the concentration of
      POM, and pH on the oxidative degradation kinetics of 4-chlorophenol in the POM
      mediated ZVI system. The POM-mediated oxidations on ZVI were additionally tested
      for 12 organic contaminants and the rates were compared. Their oxidative
      degradation on ZVI was mostly enhanced in the presence of POM (SiW12O40(4-)). The
      present study provides a good model system upon which the ZVI-based oxidation
      technologies can be successfully enhanced and modified for further developments.

PMID- 17539547
TI  - Graphite fiber brush anodes for increased power production in air-cathode
      microbial fuel cells.
AB  - To efficiently generate electricity using bacteria in microbial fuel cells
      (MFCs), highly conductive noncorrosive materials are needed that have a high
      specific surface area (surface area per volume) and an open structure to avoid
      biofouling. Graphite brush anodes, consisting of graphite fibers wound around a
      conductive, but noncorrosive metal core, were examined for power production in
      cube (C-MFC) and bottle (B-MFC) air-cathode MFCs. Power production in C-MFCs
      containing brush electrodes at 9600 m2/m3 reactor volume reached a maximum power
      density of 2400 mW/m2 (normalized to the cathode projected surface area), or 73
      W/m3 based on liquid volume, with a maximum Coulombic efficiency (CE) of 60%.
      This power density, normalized by cathode projected area, is the highest value
      yet achieved by an air-cathode system. The increased power resulted from a
      reduction in internal resistance from 31 to 8 Q. Brush electrodes (4200 m2/m3)
      were also tested in B-MFCs, consisting of a laboratory media bottle modified to
      have a single side arm with a cathode clamped to its end. B-MFCs inoculated with
      wastewater produced up to 1430 mW/m2 (2.3 W/m3, CE = 23%) with brush electrodes,
      versus 600 mW/m2 with a plain carbon paper electrode. These findings show that
      brush anodes that have high surface areas and a porous structure can produce high
      power densities, and therefore have qualities that make them ideal for scaling up
      MFC systems.

PMID- 17539548
TI  - Tubular membrane cathodes for scalable power generation in microbial fuel cells.
AB  - One of the greatest challenges for using microbial fuel cells (MFCs) for
      wastewater treatment is creating a scalable architecture that provides large
      surface areas for oxygen reduction at the cathode and bacteria growth on the
      anode. We demonstrate here a scalable cathode concept by showing that a tubular
      ultrafiltration membrane with a conductive graphite coating and a nonprecious
      metal catalyst (CoTMPP) can be used to produce power in an MFC. Using a carbon
      paper anode (surface area Aan = 7 cm2, surface area per reactor volume Aan,s = 25
      m2/m3), an MFC with two 3-cm tube cathodes (Acat = 27 cm2, Acat,s = 84 m2/m3)
      generated up to 8.8 W/m3 (403 mW/m2) using glucose [0.8 g/L in a 50 mM phosphate
      buffer solution (PBS)], which was only slightly less than that produced using a
      carbon paper cathode with a Pt catalyst (9.9 W/m3, 394 mW/m2; Acat= 7 cm2,
      Acat,s= 25 m2/m3). Coulombic efficiencies (CEs) with carbon paper anodes were 25
      40% with tube cathodes (CoTMPP), compared to 7-19% with a carbon paper cathode.
      When a high-surface-area graphite brush anode was used (Aan = 2235 cm2, Aan,s =
      7700 m2/m3) with two tube cathodes placed inside the reactor (Acat = 27 cm2,
      Acas, = 93 m2/m3), the MFC produced 17.7 W/m3 with a CE = 70-74% (200 mM PBS).
      Further increases in the surface area of the tube cathodes to 54 cm2 (120 m2/m3)
      increased the total power output (from 0.51 to 0.83 mW), but the increase in
      volume resulted in a constant volumetric power density (approximately 18 W/m3).
      These results demonstrate that an MFC design using tubular cathodes coated with
      nonprecious metal catalysts, and brush anodes, is a promising architecture that
      is intrinsically scalable for creating larger systems. Further increases in power
      output will be possible through the development of cathodes with lower internal
      resistances.

PMID- 17539549
TI  - Biological denitrification in microbial fuel cells.
AB  - Microbial fuel cells (MFCs) that remove carbon as well as nitrogen compounds out
      of wastewater are of special interest for practice. We developed a MFC in which
      microorganisms in the cathode performed a complete denitrification by using
      electrons supplied by microorganisms oxidizing acetate in the anode. The MFC with
      a cation exchange membrane was designed as a tubular reactor with an internal
      cathode and was able to remove up to 0.146 kg NO(3-)-N m(-3) net cathodic
      compartment (NCC) d(-1) (0.080 kg NO(3-)-N m(-3) total cathodic compartment d(-1)
      (TCC)) at a current of 58 A m(-3) NCC (32 A m(-3) TCC) and a cell voltage of
      0.075 V. The highest power output in the denitrification system was 8 W m(-3) NCC
      (4 W m(-3) TCC) with a cell voltage of 0.214 V and a current of 35 A m(-3) NCC.
      The denitrification rate and the power production was limited bythe cathodic
      microorganisms, which only denitrified significantly at a cathodic electrode
      potential below 0 V versus standard hydrogen electrode (SHE). This is, to our
      knowledge, the first study in which a MFC has both a biological anode and cathode
      performing simultaneous removal of an organic substrate, power production, and
      complete denitrification without relying on H2-formation or external added power.

PMID- 17539550
TI  - Effects of genotype and transpiration rate on the uptake and accumulation of
      perchlorate (ClO4-) in lettuce.
AB  - Although evidence of perchlorate accumulation in plants exists, there is a
      scarcity of information concerning the key factors and mechanisms involved. To
      ascertain whether genotypic variation in perchlorate accumulation occurs within
      lettuce, hydroponic plant uptake experiments were conducted with five types of
      lettuce (Lactuca sativa L.), which were grown to market size atthree perchlorate
      (ClO4-) concentrations (1, 5, or 10 microg/L). Perchlorate accumulated in the
      leafy tissues to varying amounts, ranging from 4 to 192 microg/kg fresh weight
      (FW), and the ranking of perchlorate accumulation was crisphead > butter head >
      romaine > red leaf > green leaf. The effect of transpiration rate on perchlorate
      accumulation was further examined using crisphead, butter head, and green leaf
      lettuce. By growing lettuce in controlled-environment chambers with two climatic
      regimes, "cloudy, humid, cool" (80% RH, 18/15 degrees C, 250 micromol/m2s
      photosynthetic photon flux density (PPFD)) and "sunny, dry, warm" (approximately
      50% RH, 28/18 degrees C, 500 micromol/m2s PPFD), up to 2.7-fold differences in
      transpiration rates were achieved. Across all three genotypes, the plants that
      transpired more water accumulated more perchlorate on a whole-head basis;
      however, the effect of transpiration rate on perchlorate accumulation was not as
      great as expected. Despite 2.0-2.7-fold differences in transpiration rate, there
      were only 1.2-2.0-fold differences in perchlorate accumulation. In addition to
      whole-head analysis, plants were sectioned into inner, middle, and outer leaves
      and processed separately. Overall, the ranking of perchlorate accumulation was
      outer leaves > middle leaves > inner leaves. Transpiration rate has a clear
      effect on perchlorate accumulation in lettuce, but other factors are influential
      and deserve exploration.

PMID- 17539551
TI  - Functional associations between two estrogen receptors, environmental estrogens,
      and sexual disruption in the roach (Rutilus rutilus).
AB  - Wild male roach (Rutilus rutilus) living in U.K. rivers contaminated with
      estrogenic effluents from wastewater treatment works show feminized responses and
      have a reduced reproductive capability, but the chemical causation of sexual
      disruption in the roach has not been established. Feminized responses were
      induced in male roach exposed to environmentally relevant concentrations of the
      pharmaceutical estrogen 17alpha-ethinylestradiol, EE2 (up to 4 ng/ L), during
      early life (from fertilization to 84 days posthatch, dph), and these effects were
      signaled by altered patterns of expression of two cloned roach estrogen receptor
      (ER) subtypes, ERalpha. and ERbeta, in the brain and gonad/ liver.
      Transactivation assays were developed for both roach ER subtypes and the
      estrogenic potencies of steroidal estrogens differed markedly at the different ER
      subtypes. EE2 was by far the most potent chemical, and estrone (E1, the most
      prevalent environmental steroid in wastewater discharges) was equipotent with
      estradiol (E2) in activating the ERs. Comparison of the EC50 values for the
      compounds tested showed that ERbeta was 3-21-fold more sensitive to natural
      steroidal estrogens and 54-fold more sensitive to EE2 as compared to ERalpha.
      These findings add substantial support to the hypothesis that steroidal estrogens
      play a significant role in the induction of intersex in roach populations in U.K.
      rivers and that the molecular approach described could be usefully applied to
      understand interspecies sensitivity to xenoestrogens.

PMID- 17539552
TI  - Direct sampling of organisms from the field and knowledge of their phenotype: key
      recommendations for environmental metabolomics.
AB  - Critical questions must be addressed to evaluate the potential of metabolomics
      for studying free-living wildlife. First, can metabolomics identify stress
      induced phenotypes in animals experiencing a highly variable environment or must
      animals be stabilized in a controlled laboratory prior to sampling? Second, is
      knowledge of species and phenotype (gender and age) required to interpret
      metabolomics data? To address these questions, we characterized the metabolic
      variability of the mussel and determined if inherent variability masked the
      metabolic response to an environmental stressor, hypoxia. Specifically, we
      compared metabolic fingerprints of adductor muscle and mantle from four groups of
      Mytilus galloprovincialis: animals sampled directly from the field with and
      without hypoxia and those stabilized in a laboratory for 60 h, also with and
      without hypoxia. Contrary to expectation, laboratory stabilization increased
      metabolic variability in adductor muscle, thereby completely masking the response
      to hypoxia. The principal source of metabolic variability in mantle was shown to
      be gender-based, highlighting the importance of phenotypic anchoring of samples
      to known life history traits. We conclude that direct field sampling is
      recommended for environmental metabolomics since it minimizes metabolic
      variability and enables stress-induced phenotypic changes to be observed.
      Furthermore, we recommend that species and phenotype of the study organism must
      be known for meaningful interpretation of metabolomics data.

PMID- 17539553
TI  - Characterization of a radiation-induced stress response communicated in vivo
      between zebrafish.
AB  - Radiation-induced communication of stress signals between rainbow trout
      (Oncorhynchus mykiss W) have recently been described by this group and linked to
      the bystander effect. This paper addresses the question of whether another
      totally unrelated fish species (Danio rerio L) can demonstrate the effect and
      also looks at attenuation of both the bystander signal, from irradiated fish, and
      the bystander effect, in naive fish. The data show that zebrafish produce
      bystander signals, and that, as with rainbow trout these can affect naive (i.e.,
      non-irradiated) fish placed in water with X-rayed fish or in water previously
      occupied by X-rayed fish. Skin explants from directly X-rayed fish still reduce
      HPV-G reporter cell growth 6 h after X-ray, but the bystander signal to naive
      fish is lost. Twelve h after X-ray the signal is lost in X-rayed fish. The
      bystander effect is also attenuated if induction was by placing naive fish in
      water which previously held the X-rayed fish. However, the effect is retained if
      induction was by placing X-rayed and naive fish together. This suggests the
      signal is not retained by water for long periods of time. Individual fish data
      reveal unique responses by bystander fish which could indicate varying levels of
      sensitivity to signal strength among individuals.

PMID- 17539554
TI  - Comment on "Misinterpretation of drinking water quality monitoring data with
      implications for risk management".

PMID- 17539555
TI  - Comment on "Partitioning and bioaccumulation of PBDEs and PCBs in lake Michigan".

PMID- 17539556
TI  - Special report: quality of care survey. Doctors say many obstacles block paths to
      patient safety.

PMID- 17539557
TI  - Special report: quality of care survey. Challenges in patient safety and quality:
      replacing discouragement with hope.

PMID- 17539558
TI  - The reality of the hospital: physician leaders in harm's way.

PMID- 17539559
TI  - Special report: quality of care survey. Quality models: selecting the best model
      to deliver results.

PMID- 17539560
TI  - Special report: quality of care survey. Improving patient flow.

PMID- 17539561
TI  - Increasing physician engagement. Using norms of physician culture to improve
      relationships with medical staff.
AB  - Comments on the 2004 survey identified that physicians thought it was too early
      to judge whether the new structure itself was successful. This year, the survey
      will be repeated to measure the effectiveness of the new structure and to help
      administrators set goals to further improve physician engagement levels.
      Meanwhile, Mercy & Unity is using the tenets of the physician compact, elements
      of physician culture, and elements of administrative culture to inform new
      process-improvement activities. More study is needed to identify whether Mercy &
      Unity's techniques of reorganization contributed to the higher rates of physician
      satisfaction and engagement, but it is our belief that incorporating physician
      cultural norms into the process helped prevent the change process from turning
      the horse into the proverbial camel.

PMID- 17539562
TI  - Dilemmas of cooperation for physician leaders.

PMID- 17539563
TI  - How to make innovation happen--Part 2.

PMID- 17539564
TI  - Effectively integrating your EMR initiative.

PMID- 17539565
TI  - Strategic planning: it's what's for dinner.

PMID- 17539566
TI  - Nanotechnology: science fiction? Or next challenge for the ethics committee?

PMID- 17539567
TI  - People persons--and the job interview.

PMID- 17539568
TI  - The broadening horizon for physician executives: the six constituencies of health
      care.

PMID- 17539569
TI  - Peer review immunity? Think again: recent developments in federal and state law.

PMID- 17539570
TI  - Organizational success = "4 + 2".

PMID- 17539571
TI  - Health literacy: how are your patients reading you?
AB  - Health literacy is much more than the basic ability to read and understand
      medical instructions. True health literacy is a vital component of patient
      centered care-care that is responsive to patients' needs and values.

PMID- 17539572
TI  - What makes a great board chair?
AB  - The chair creates the climate of the board--and great ones can make virtually
      every aspect of their organization better.

PMID- 17539573
TI  - Care with compassion. The case for palliative care.
AB  - As the population ages, and complex, chronic conditions become more prevalent in
      the patient mix, hospitals need to take a sharper look at the advantages--and
      common sense--of palliative care.

PMID- 17539574
TI  - Better governance begins with greater board diversity.

PMID- 17539575
TI  - How to make a board retreat pay dividends.
AB  - Board retreats offer trustees and senior management an exceptional environment
      for fostering both relationships and insights.

PMID- 17539576
TI  - What's in a brand?
AB  - Strategic Planning: When your hospital's name is synonymous with your highest
      goals, you may have achieved "branding" success.

PMID- 17539577
TI  - What boards need to know about regulatory issues.
AB  - EMTALA: The first in a gatefold series explaining what boards need to know about
      regulatory issues.

PMID- 17539578
TI  - A robotic testing facility for the measurement of the mechanics of spinal joints.
AB  - A robotic testing facility for the measurement of joint mechanics was used to
      determine the significance of tears in the intervertebral disc on the mechanics
      of the spinal joint. Ten lumbar joints of sheep were dynamically loaded and
      manipulated. Comparisons were made between the behaviour of the intervertebral
      disc in flexion and extension at two test speeds. The influence of the posterior
      elements and of rim lesions was assessed by testing the joint immediately before
      and after removal of the posterior elements and after the creation of a 4 mm x 10
      mm rim lesion in the disc. Stiffness of the spinal joint dropped significantly
      upon removal of the posterior elements, from 0.81 to 0.23 N m/deg for flexion and
      from 0.65 to 0.40 N m/deg for extension. Maximum moments dropped 37 per cent for
      flexion and 63 per cent for extension. The rim lesion caused a further
      significant stiffness reduction to 0.21 and 0.31 N m/deg respectively. Maximum
      moments reduced a further 12 per cent and 16 per cent respectively. A higher test
      speed (2 deg/s instead of 0.5 deg/s) usually did not change these results
      significantly. The novel six-degrees-of-freedom robotic testing facility used in
      this study was demonstrated to be an effective system for studying the mechanics
      of complex biological joints.

PMID- 17539579
TI  - Increase of load-carrying capacity under follower load generated by trunk muscles
      in lumbar spine.
AB  - The load-carrying capacity of the spine has been experimentally shown to increase
      substantially when the resultant force of all loads applied on the spine is
      directed in accordance to its curvature, which is called a 'follower load (FL)'.
      However, there have been few studies to investigate the muscle forces producing
      the FL owing to the difficulty of the relevant experimental measurements. This
      study investigated whether trunk muscle activations could be found for
      transmitting an external load within a range of FL direction. A two-dimensional
      finite element model of a lumbar spine and 117 pairs of trunk muscles was
      developed in the sagittal plane. An optimization technique was utilized to
      estimate the muscle forces generating the FL and the corresponding responses of
      the lumbar spine under two loading cases: the upright neutral standing posture
      and the posture holding 200 N in the hands. For each loading case, the muscle
      forces required to generate the FL could be found and the corresponding responses
      of the lumbar spine validated that the FL could increase the load-carrying
      capacity. The results showed that the FL could be produced in vivo by trunk
      muscles to increase the load-carrying capacity.

PMID- 17539580
TI  - Concentric and eccentric shoulder rehabilitation biomechanics.
AB  - The use of an impulse-momentum (IM) exercise technique was investigated for end
      stage shoulder rehabilitation. The objectives of this study were to: (a) quantify
      the net shoulder joint forces and moments while using an IM system and (b) test
      the influence of gender and muscle loading type (concentric or eccentric) on
      kinetic and kinematic parameters. Fourteen healthy adults (eight males, six
      females) performed a repeated measures experiment on an instrumented device
      utilizing a cabled shuttle system. While maintaining 90 degrees of shoulder
      abduction and 90 degrees of elbow flexion, the subjects externally rotated their
      upper arm from 0 degrees to 90 degrees (concentric acceleration) and then
      internally rotated their upper arm back from 90 degrees to the 0 degrees position
      (eccentric deceleration). Shoulder joint forces and moments as well as rotational
      work and power were calculated using inverse dynamics (free-body forces and
      moments calculated at intersegmental joint centres). Overall concentric peak
      forces and moments were greater than eccentric peak forces and moments (P <
      0.0001). Joint forces and moments reached a maximum during the initial phase of
      concentric loading (0 degrees to 45 degrees) compared with any other rotational
      position in the loading cycle (concentric 45 degrees to 90 degrees or eccentric
      90 degrees to 0 degrees). The results also indicate that males experienced higher
      (P < 0.0001) average resultant peak joint forces (concentric 0 degrees to 45
      degrees = 108.0 N and eccentric 90 degrees to 45 degrees = 87.2 N) than females
      (concentric 0 degrees to 45 degrees = 74.7 N and eccentric 45 degrees to 0
      degrees = 56.0 N). In addition, males experienced higher (P < 0.0001) average
      resultant peak joint moments (concentric 0 degrees to 45 degrees = 30.4 N m and
      eccentric 45 degrees to 0 degrees = 21.0 N m) than females (concentric 0 degrees
      to 45 degrees = 19.7 N m and eccentric 45 degrees to 0 degrees = 12.8 N m).

PMID- 17539581
TI  - Ultrasonic characterization of the mechanical properties and polymerization
      reaction of acrylic-based bone cements.
AB  - In this investigation the pulse-echo technique was validated as a method that
      could be used to monitor the complete polymerization of acrylic bone cement in a
      surgical theatre. Currently, orthopaedic surgeons have no objective method to
      quantify the state of cure of bone cement as it progresses through its
      polymerization cycle. Clear benefits of the pulse-echo technique are that it is
      easy to use, non-invasive, and non-destructive. Furthermore, the test results
      were found to be highly reproducible with minor deviations. Three proprietary
      cements were used to confirm the validity of the technique; CMW Endurance,
      Palacos R and Simplex P. The results showed that the acoustic properties of bone
      cement clearly demonstrated a relationship with the different stages of
      polymerization, and in particular with the transitions between the waiting,
      dough, and setting phases. Additionally, the cure time of the poly(methyl
      methacrylate) cements consistently correlated with the attainment of 75 per cent
      of the average maximum velocity of sound value. The measured cure times concurred
      with the ISO and ASTM standards. Moreover, measurements of the final sound
      velocity and broadband ultrasonic attenuation correlated strongly with the
      density and mechanical properties of the cured bone cement samples.

PMID- 17539582
TI  - Investigation of the friction and surface degradation of innovative chondroplasty
      materials against articular cartilage.
AB  - Understanding the wear of the biomaterial-cartilage interface is vital for the
      development of innovative chondroplasty. The aim of this study was to investigate
      a number of biphasic materials as potential chondroplasty biomaterials. Simple
      geometry friction and wear studies were conducted using bovine articular
      cartilage pins loaded against a range of single-phase and biphasic materials. The
      frictions of each biomaterial was compared within simple and protein-containing
      lubricants. Longer-term continuous sliding tests within a protein containing
      lubricant were also conducted at various loading conditions to evaluate the
      friction and degradation for each surface. All single-phase materials showed a
      steady rise in friction, which was dependent on the loss of interstitial fluid
      load support from the opposing cartilage pin. All biphasic materials demonstrated
      a marked reduction in friction when compared with the single-phase materials. It
      is postulated that the biphasic nature of each material allowed an element of
      fluid load support to be maintained by fluid rehydration and expulsion. In the
      longer-term study, significant differences in the articular cartilage pin
      (surface damage) between the positive control (stainless steel) and the negative
      control (articular cartilage) was found. The potential biphasic chondroplasty
      materials produced a reduction in articular cartilage pin damage when compared
      with the single-phase materials. The changes in surface topography of the
      cartilage pin were associated with increased levels of friction achieved during
      the continuous wear test. The study illustrated the importance of the biphasic
      properties of potential chondroplasty materials, and future work will focus on
      the optimization of biphasic properties as well as long-term durability, such
      that materials will more closely mimic the biotribology of natural articular
      cartilage.

PMID- 17539583
TI  - The wear properties of CFR-PEEK-OPTIMA articulating against ceramic assessed on a
      multidirectional pin-on-plate machine.
AB  - In an attempt to prolong the lives of rubbing implantable devices, several 'new'
      materials have been examined to determine their suitability as joint couplings.
      Tests were performed on a multidirectional pin-on-plate machine to determine the
      wear of both pitch and PAN (polyacrylonitrile)-based carbon fibre reinforced
      polyetheretherketone (CFR-PEEK-OPTIMA) pins articulating against both BioLox
      Delta and BioLox Forte plates (ceramic materials). Both reciprocation and
      rotational motion were applied to the samples. The tests were conducted using
      24.5 per cent bovine serum as the lubricant (protein concentration 15 g/l).
      Although all four material combinations gave similar low wear with no
      statistically significant difference (p > 0.25), the lowest average total wear of
      these pin-on-plate tests was provided by CFR-PEEK-OPTIMA pitch pins versus BioLox
      Forte plates. This was much lower than the wear produced by conventional joint
      materials (metal-on-polyethylene) and metal-on-metal combinations when tested on
      the pin-on-plate machine. This therefore indicates optimism that these PEEK
      OPTIMA-based material combinations may perform well in joint applications.

PMID- 17539584
TI  - An analysis of the in vivo deterioration of Co-Cr-Mo implants through wear and
      corrosion.
AB  - The degradation of Co-Cr-Mo ASTM F75-92 hip implants after a harvesting period of
      81 months in sheep was investigated. Hip prostheses and tissue samples were
      obtained from a medical study involving total hip arthroplasty of the cemented
      type in 12 sheep. Upon euthanasia, the explants were retrieved for analyses of
      the surfaces and evidence of degradation, while tissue samples from the interface
      regions were harvested for chemical analysis and evidence of Co, Cr, and Mo
      contents. Clear evidence of wear and corrosion was detected. Results also
      indicated that the modes of metal transport through the poly(methyl methacrylate)
      bone cement play an important role as the surface degradation mechanisms of the
      metal. The results are being discussed in terms of electrochemical and
      triboelectrochemical behaviour of the Co-Cr-Mo alloy.

PMID- 17539585
TI  - The influence of femoral condylar lift-off on the wear of artificial knee joints.
AB  - In vivo fluoroscopic studies of patients with total knee replacements (TKRs) have
      shown lift-off of the femoral condyles from the tibial insert. This study
      investigated the influence of femoral condylar lift-off on the ultra-high
      molecular weight polyethylene (UHMWPE) wear of fixed bearing (FB) and rotating
      platform mobile bearing (RP MB) total knee replacements, using a physiological
      knee joint simulator. In the absence of lift-off, the RP MB knees exhibited a
      lower wear rate of 5.2 +/- 2.2 mm3 per million cycles (mm3/MC) compared with 8.8
      +/- 4.8 mm3/MC for the FB knees. The presence of femoral condylar lift-off was
      found to accelerate the wear of the FB and RP MB knees tested in this study to
      16.4 +/- 2.9 and 16.9 +/- 2.9 mm3/MC respectively. For the RP MB knees the
      increase in wear rate was more marked, resulting in a similar wear rate for both
      designs of knee under lift-off conditions. In both cases the medial condyle
      displayed more wear damage. This study has shown that a small amount of
      abduction/adduction lift-off and medial-lateral shift increases wear and that the
      increase in wear is design dependent. In this simulator test, lift-off was
      simulated on every cycle, whereas the amount of wear and effect of lift-off
      clinically would depend on the frequency of occurrence of lift-off in vivo.

PMID- 17539586
TI  - Experimental validation of a finite element model of a composite tibia.
AB  - Composite bones are synthetic models made to simulate the mechanical behaviour of
      human bones. Finite element (FE) models of composite bone can be used to evaluate
      new and modified designs of joint prostheses and fixation devices. The aim of the
      current study was to create an FE model of a composite tibia and to validate it
      against results obtained from a comprehensive set of experiments. For this, 17
      strain rosettes were attached to a composite tibia (model 3101, Pacific Research
      Laboratories, Vashon, Washington, USA). Surface strains and displacements were
      measured under 13 loading conditions. Two FE models were created on the basis of
      computed tomography scans. The models differed from each other in the mesh and
      material properties assigned. The experiments were simulated on them and the
      results compared with experimental results. The more accurate model was selected
      on the basis of regression analysis. In general, experimental strain measurements
      were highly repeatable and compared well with published results. The more
      accurate model, in which the inner elements representing the foam were assigned
      isotropic material properties and the elements representing the epoxy layer were
      assigned transversely isotropic material properties, was able to simulate the
      mechanical behaviour of the tibia with acceptable accuracy. The regression line
      for all axial loads combined had a slope of 0.999, an intercept of -6.24
      microstrain, and an R2 value of 0.962. The root mean square error as a percentage
      was 5 per cent.

PMID- 17539587
TI  - Assuming exponential decay by incorporating viscous damping improves the
      prediction of the coefficient of friction in pendulum tests of whole articular
      joints.
AB  - A pendulum test with a whole articular joint serving as the fulcrum is commonly
      used to measure the bulk coefficient of friction (COF). In such tests it is
      universally assumed that energy loss is due to frictional damping only, and
      accordingly the decay of pendulum amplitude is linear with time. The purpose of
      this work was to determine whether the measurement of the COF is improved when
      viscous damping and exponential decay of pendulum amplitude are incorporated into
      a lumped-parameter model. Various pendulum models with a range of values for COF
      and for viscous damping were constructed. The resulting decay was fitted with an
      exponential function (including both frictional and viscous damping) and with a
      linear decay function (frictional damping only). The values predicted from the
      fit of each function were then compared to the known values. It was found that
      the exponential decay function was able to predict the COF values within 2 per
      cent error. This error increased for models in which the damping coefficient was
      relatively small and the COF was relatively large. On the other hand, the linear
      decay function resulted in large errors in the prediction of the COF, even for
      small values of viscous damping. The exponential decay function including both
      frictional and constant viscous damping presented herein dramatically increased
      the accuracy of measuring the COF in a pendulum test of modelled whole articular
      joints.

PMID- 17539588
TI  - [Suicides in East Berlin from 1980 to 1989].
AB  - In the analysed period from 1980 to 1989, 3.480 suicides (= 34.6%) were among the
      10.064 corpses admitted to the Institute of Legal Medicine of the Humboldt
      University in Berlin. The share of men who committed suicide was higher than the
      share of women with the average ratio being 1.4:1. The preferred suicide method
      in men was hanging and in women drug intoxication. The decrease of the formerly
      common carbon monoxide poisoning is attributable to the switch from town gas to
      natural gas. Autopsies showed that only about one third of the individuals who
      had committed suicide had been under the influence of alcohol at the time of
      death. In most cases the suicides were committed in the suicides' own flat. It
      also turned out that there was a seasonal peak of suicides in spring.

PMID- 17539589
TI  - [Fatal chest injury from a shotgun slug: homicide, accident or suicide?].
AB  - A 78-year-old hunter was found dead beside his raised hide with a gunshot wound
      to his chest. In the present case, the reconstruction of the shooting event
      revealed an accident. Disregarding all safety rules, the hunter had placed his
      superposed rifle-shotgun on the chair and pulled the barrels of the cocked gun
      towards his body. One of the triggers interlocked with the button of a camping
      chair's cushion and a shot was fired. Furthermore the morphology of wounds from
      shotgun slugs is discussed on the basis of the autopsy findngs.

PMID- 17539590
TI  - [Analysis of mitochondrial SNPs in addition to conventional STR-typing in a case
      of aggravated theft].
AB  - In the field of forensic DNA typing, the analysis of Short Tandem Repeats (STRs)
      can fail in cases of degraded DNA. The typing of coding region Single Nucleotide
      Polymorphisms (SNPs) of the mitochondrial genome provides an approach to acquire
      additional information. In the examined case of aggravated theft, both suspects
      could be excluded of having left the analyzed hair on the crime scene by SNP
      typing. This conclusion was not possible subsequent to STR typing. SNP typing of
      the trace on the torch light left on the crime scene increased the likelihood for
      suspect no. 2 to be the origin of this trace. This finding was already indicated
      by STR analysis. Suspect no. 1 was excluded for being the origin of this trace by
      SNP typing which was also indicated by STR analysis. A limiting factor for the
      analysis of SNPs is the maternal inheritance of mitochondrial DNA.
      Individualisation is not possible. In conclusion, it can be said that in the case
      of traces which cause problems with conventional STR typing the supplementary
      analysis of coding region SNPs from the mitochondrial genome is very reasonable
      and greatly contributes to the refinement of analysis methods in the field of
      forensic genetics.

PMID- 17539591
TI  - [Fictitious ambush following an attempted "extended" suicide].
AB  - An unusual case of a 31-year-old-woman who was found near a forest road with self
      inflicted injuries and burns is reported. The woman claimed to have been attacked
      by a man with a knife who then tried to burn her in her car. While she managed to
      escape, her cat died in the car. The examination of the wounds showed multiple
      superficial cuts in body regions easily accessible to her own hand. Gas
      chromatography of skin samples from the cat proved that it had been in in contact
      with a fire accelerant. On the basis of the examination findings, differential
      diagnostic aspects with regard to the motivation of the woman for simulating an
      offence are discussed. In all probability, the woman intended to commit suicide
      together with the cat through self-immolation, but did not complete the plan.

PMID- 17539592
TI  - [Suicide with acetylsalicylic acid].
AB  - The authors report on a suicide of a 41-year-old man with acetylsalicylic acid.
      According to his own statement the man had taken about 200 tablets of Aspirin (65
      g acetylsalicylic acid) and initially showed no symptoms of intoxication. 4-5
      hours after ingestion he vomited twice, but clear intoxication symptoms like
      convulsions and cardiac arrhythmia occurred not earlier than 11 hours after
      ingestion. Resuscitation by the emergency physician was not successful. The
      chemical-toxicological analysis (HPLC-DAD) of blood samples taken in the hospital
      approximately 12 h after ingestion showed salicylate in concentrations of 475
      mg/L to 557 mg/L. The post-mortem concentrations of salicylate were within the
      lethal-toxic range, i.e. 762 mg/L in heart blood and 215 mg/L in femoral blood.
      All tested organs contained equally lethal salicylate levels (e.g. 503 mg/L in
      the liver and 251 mg/L in the brain).

PMID- 17539593
TI  - [Suicidal gunshot to the head while driving a car].
AB  - A severe traffic accident occurred on the German autobahn. According to eye
      witnesses, the car had changed from the left to the right lane at 160 km/h before
      crashing into a thicket at full speed. In the car, a sports pistol was found in
      the footwell of the driver's side. The emergency doctor who performed the
      external examination of the victim's body found a gunshot wound in the region of
      the driver's right lower jaw. As the prosecutor released the body without further
      examination, the family of the suicide asked for an autopsy, which demonstrated a
      lethal suicidal gunshot to the head; toxicological tests proved a previous
      consumption of cocaine.

PMID- 17539594
TI  - Pattern recognition in retrosynthetic analysis: snapshots in total synthesis.
AB  - In this Perspective, the value of small molecule natural products (SMNPs) in the
      discovery of active biological agents is discussed. The usefulness of the natural
      products-based method of potential pharma discovery is much augmented by the
      capacities of chemical synthesis. The great advances in synthetic methodology
      allow for major editing of the natural product in the hopes of optimizing potency
      and therapeutic index. As a consequence of the enormous increase in the power of
      multistep chemical synthesis, one can now approach structures of previously
      impractical complexity. In constructing a plan for a multistep synthesis, two
      complementary thought styles are often encountered. One is the traditional and
      extremely powerful concept of prioritized strategic bond disconnections. The
      other, which we term "pattern recognition," involves the identification of
      moieties within the target, which are associated with reliable chemistry, and can
      serve to facilitate progress to the target. Recognition of such targets may
      require substantial recasting of the target structure to connect it to well
      established types of transformations. Some of our older ventures, where ideas
      about pattern recognition were first being fashioned and used productively, are
      revisited. In addition, we provide snapshots of recently achieved total syntheses
      of SMNPs of novel biological potential. These vignettes serve to harmonize
      insights occasioned by pattern recognition, in concert with transformations
      enabled by the enormous growth in the power of synthesis.

PMID- 17539595
TI  - Studies on aminoisonucleoside modified siRNAs: stability and silencing activity.
AB  - A novel class of aminoisonucleoside was synthesized and incorporated into a
      luciferase gene-targeting siRNA. Structural and functional analyses of such a
      kind of siRNAs indicated that sense strand modifications with aminoisonucleoside
      at the 3' or 5' terminal, such as ssIso-1 and ssIso-2, have less effect on RNA
      duplex thermal and serum stabilities, and their functional activities are also
      comparable to their native siRNAs. In contrast, antisense strand modifications
      with aminoisonucleoside at the corresponding positions, such as asIso-2 or asIso
      1, bring a striking negative effect on RNA duplex stability but still maintain
      around 40-50% of gene knockdown.

PMID- 17539596
TI  - A database of historically-observed chemical replacements.
AB  - A systematic analysis of one-to-one chemical replacements occurring in a set of
      50,000 druglike molecules was performed. The frequency of occurrence, as well as
      the average change in measured and calculated properties, was computed for each
      observed substitution. The experimental properties considered were solubility,
      protein binding, and logD. The calculated properties were logP, molecular weight,
      number of hydrogen bond donors and acceptors, and polar surface area. During this
      analysis, in which 9000 different functional groups were considered, 0.7 million
      substitutions were identified and stored in a database. As an application, we
      present a web interface from which users can identify historically observed
      replacements of any functional group on their query molecule. The server returns
      a list of side-chains, as well as the historically observed shift in experimental
      properties.

PMID- 17539597
TI  - Structural study of the DNA dipalmitoylphosphatidylcholine complex at the air
      water interface.
AB  - We present here results that demonstrate the formation of a complex of DNA with
      zwitterionic dipalmitoylphosphatidylcholine (DPPC) monolayer at the air-water
      interface in the presence of Ca2+ ions; in particular, we show that the presence
      of Ca2+ cations is essential for the formation of the complex of DPPC with DNA.
      We characterize the resulting structure by X-ray reflectivity and by null
      ellipsometry. We show that DNA maintains its native double helix form when
      attached to the zwitterionic lipid monolayer, at difference with the case of
      ammine containing monolayers. Our findings are discussed in view of other works
      that recently appeared on the interaction of DNA with zwitterionic phospholipids,
      emphasizing the role of DPPC as a potential vector for transfer of genetic
      material into mammalian cells by nonviral gene therapy and also suggesting
      Langmuir/Blodgett layers of zwitterionic phospoholipids as a method for
      nonconventional DNA immobilization.

PMID- 17539598
TI  - Bioluminescent indicator for determining protein-protein interactions using
      intramolecular complementation of split click beetle luciferase.
AB  - Click beetle luciferase (CBLuc) is insensitive to pH, temperature, and heavy
      metals, and emits a stable, highly tissue-transparent red light with luciferin in
      physiological circumstances. Thus, the luminescence signal is optimal for a
      bioanalytical index reporting the magnitude of a signal transduction of interest.
      Here, we validated a single-molecule-format complementation system of split CBLuc
      to study signal-controlled protein-protein (peptide) interactions. First, we
      generated 10 pairs of N- and C-terminal fragments of CBLuc to examine
      respectively whether a significant recovery of the activity occurs through the
      intramolecular complementation. The ligand binding domain of androgen receptor
      (AR LBD) was connected to a functional peptide sequence through a flexible
      linker. The fusion protein was then sandwiched between the dissected N- and C
      terminal fragments of CBLuc. Androgen induces the association between AR LBD and
      a functional peptide and the subsequent complementation of N- and C-terminal
      fragments of split CBLuc inside the single-molecule-format probe, which restores
      the activities of CBLuc. The examination about the dissection sites of CBLuc
      revealed that the dissection positions next to the amino acids D412 and I439
      admit a stable recovery of CBLuc activity through an intramolecular
      complementation. The ligand sensitivity and kinetics of the single molecular
      probe with split CBLuc were discussed in various cell lines and in different
      protein-peptide binding models. The probe is applicable to developing
      biotherapeutic agents on the AR signaling and for screening adverse chemicals
      that possibly influence the signal transduction of proteins in living cells or
      animals.

PMID- 17539599
TI  - Open-tubular capillary electrochromatography coupled with electrospray ionization
      mass spectrometry for peptide analysis.
AB  - In this study, the open-tubular electrochromatographic (OT-CEC) migration
      behavior of various peptides has been characterized using etched and chemically
      (n-octadecyl- and cholesterol-) modified capillaries, interfaced to an
      electrospray ionization mass spectrometer through a sheath liquid configuration.
      The stationary phases were fabricated by etching the inner wall of the fused
      silica capillary and then chemically modifying the new surface through a
      silanization/hydrosilation reaction. Unlike some other OT-CEC stationary-phase
      preparation methods, leaching of the immobilized stationary phase and subsequent
      contamination of the electrospray ion source was largely avoided with this novel
      surface modification technology. The influence of the immobilized organic phases
      and those of the buffer electrolytes (pH, the type and content of organic
      solvent) on the retention and separation of the selected peptides was
      investigated. Significant peptide retention was found even at very low pH with
      both types of stationary phases, under conditions whereby the electrophoretic
      migration dominated the separation process. Due to the effective coverage of the
      etched surface by a silanization/hydrosilation reaction, adverse adsorption of
      charged analytes onto the capillary wall was minimized. As a result, very
      efficient and highly reproducible peptide separations were achieved over a broad
      pH range. Moreover, peptide-specific multizoning effects were observed. The
      origin of this novel phenomenon was explored. Compared to capillary
      electrophoresis electrospray ionization mass spectrometry system, much higher
      detection sensitivity could be obtained, since a larger amount of sample could be
      injected and stacked at the head of the open-tubular capillary column without
      deteriorating the separation performance. On the basis of these observations,
      these procedures have been adapted to allow the analysis of tryptic peptides
      generated from proteins.

PMID- 17539600
TI  - Analysis of acrylamide in water using a coevaporation preparative step and
      isotope dilution liquid chromatography tandem mass spectrometry.
AB  - Acrylamide is a probable human carcinogen, and the drinking water quality
      guideline for this compound is 0.5 mg/L. However, analysis of this compound in
      water is difficult because of its very high water solubility, which limits the
      efficiency of sample preconcentration prior to analysis. We developed a robust
      and sensitive analytical method for the determination of trace quantities of
      acrylamide in samples of water using a novel preparative technique and isotope
      dilution liquid chromatography tandem mass spectrometry with atmospheric pressure
      chemical ionization as the ion source (LC-APCI-MS/MS). The preparative method
      involves coevaporation of acrylamide with water at pH 10 using a rotary
      evaporator, followed by acidification to pH 3.0 and concentration of the sample
      prior to analysis by LC-APCI-MS/MS. To compensate for the loss of the analyte
      during sample preparation and signal suppression due to interference from the
      sample matrix, isotope dilution with acrylamide-d3 was used for quantitation.
      Using this method, analyte recoveries ranged from 74 to 103% for acrylamide
      spiked into water at a concentration of 0.4 ng/mL. The limit of detection and
      limit of quantification (LOQ) for acrylamide in water were 0.02 and 0.06 ng/mL,
      respectively. This method was successfully applied to determine trace levels of
      acrylamide in samples of river water and in runoff from an agricultural field to
      which municipal biosolids (i.e., sludge) had been applied. Concentrations of
      acrylamide in these samples ranged from <LOQ to 0.16 microg/L.

PMID- 17539601
TI  - Scanning electrochemical microscopy as a readout tool for protein
      electrophoresis.
AB  - Scanning electrochemical microscopy (SECM) was used to image silver-stained
      proteins on a poly(vinylidene difluoride) membrane. The method is based on
      measuring the current at a scanning microelectrode in the feedback mode. The
      electrochemical feedback is caused by the redox-mediated etching of the isolated
      5 - 10-nm-diameter silver nanoparticles formed during the staining process.
      Several parameters, such as the redox mediator and the staining protocol, were
      optimized to ensure a high resolution and a low detection limit, i.e., 0.5 ng of
      bovine serum albumin (4 x 10(-14) mol) distributed on an area of 1 mm(2) (4 x 10(
      16) mol x cm(-2)). Images of beta-lactoglobulin A and myoglobin bands after gel
      electrophoretic separation and electroblotting were obtained in order to
      demonstrate that SECM can be employed as a sensitive and quantitative readout
      method for detection of proteins after gel electrophoresis. An additional
      advantage is that the silver staining can be removed, allowing further downstream
      mass spectrometry analysis.

PMID- 17539602
TI  - Magnetically immobilized beds for capillary electrochromatography.
AB  - Fritless packed beds comprised of magnetically responsive octadecylsilane bonded
      silica particles have been constructed for reversed-phase electrochromatography.
      The magnetic particles were immobilized in the capillary by applying an external
      magnetic field transverse to the direction of electroosmotic flow. Being
      subjected to the interplay of fluid dragging and magnetic forces, the initial
      loosely packed particle assembly was compacted into a uniform packing structure.
      The magnetically immobilized beds obtained were used as stationary phases for
      separation of neutral compounds, with retention behavior and column efficiency
      similar to those of slurry-packed columns. The results suggest that the magnetic
      attraction approach to fritless column packing may be used for construction of
      advanced chip-based chromatography, especially in complex architectures
      comprising curved and intersecting channels.

PMID- 17539603
TI  - Development of an on-line flow injection Sr/matrix separation method for
      accurate, high-throughput determination of Sr isotope ratios by multiple
      collector-inductively coupled plasma-mass spectrometry.
AB  - This work introduces a newly developed on-line flow injection (FI) Sr/Rb
      separation method as an alternative to the common, manual Sr/matrix batch
      separation procedure, since total analysis time is often limited by sample
      preparation despite the fast rate of data acquisition possible by inductively
      coupled plasma-mass spectrometers (ICPMS). Separation columns containing
      approximately 100 muL of Sr-specific resin were used for on-line FI Sr/matrix
      separation with subsequent determination of (87)Sr/(86)Sr isotope ratios by
      multiple collector ICPMS. The occurrence of memory effects exhibited by the Sr
      specific resin, a major restriction to the repetitive use of this costly
      material, could successfully be overcome. The method was fully validated by means
      of certified reference materials. A set of two biological and six geological Sr-
      and Rb-bearing samples was successfully characterized for its (87)Sr/(86)Sr
      isotope ratios with precisions of 0.01-0.04% 2 RSD (n = 5-10). Based on our
      measurements we suggest (87)Sr/(86)Sr isotope ratios of 0.713 15 +/- 0.000 16 (2
      SD) and 0.709 31 +/- 0.000 06 (2 SD) for the NIST SRM 1400 bone ash and the NIST
      SRM 1486 bone meal, respectively. Measured (87)Sr/(86)Sr isotope ratios for five
      basalt samples are in excellent agreement with published data with deviations
      from the published value ranging from 0 to 0.03%. A mica sample with a Rb/Sr
      ratio of approximately 1 was successfully characterized for its (87)Sr/(86)Sr
      isotope signature to be 0.718 24 +/- 0.000 29 (2 SD) by the proposed method.
      Synthetic samples with Rb/Sr ratios of up to 10/1 could successfully be measured
      without significant interferences on mass 87, which would otherwise bias the
      accuracy and uncertainty of the obtained data.

PMID- 17539604
TI  - Mass + retention time = structure: a strategy for the analysis of N-glycans by
      carbon LC-ESI-MS and its application to fibrin N-glycans.
AB  - Analysis of the numerous possible, often isobaric structures of protein-bound
      oligosaccharides calls for a high-performance two-dimensional method that
      combines liquid chromatography's ability to separate isomers and mass
      spectrometry's ability to determine glycan composition. Here we investigate the
      usefulness of porous graphitic carbon columns coupled to ESI-MS for the
      separation of N-glycans with two or more sialic acids. Internal standards helped
      to rectify retention time fluctuations and thus allowed elution times to play an
      essential role in the structural assignment of peaks. For generation of a
      retention time library, standards representing the possible isomers of
      diantennary non-, mono-, and disialylated N-glycans, differing in the linkage of
      galactose and sialic acids as well as isobaric hybrid-type N-glycans, were
      produced using recombinant glycosyltransferases. Once the retention times library
      was established, isomers could be identified by LC-ESI-MS in the positive mode
      without additional MS/MS experiments. The method was applied for the detailed
      structural analysis of fibrin(ogen) N-glycans from various species (human, cow,
      pig, mouse, rat, cat, dog, Chinese hamster, horse, sheep, and chicken). All
      fibrins contained diantennary N-glycans. They differed in the occurrence of
      beta1,3-linked galactose, alpha2,3-linked sialic acids, and N-glycolylneuraminic
      acid, in the mono/diantennary glycan ratio, and in the O-acetylation of
      neuraminic acids. The separation system's potential for analyzing tri- and
      tetrasialylated N-glycans was demonstrated.

PMID- 17539605
TI  - Parts-per-billion mass measurement accuracy achieved through the combination of
      multiple linear regression and automatic gain control in a Fourier transform ion
      cyclotron resonance mass spectrometer.
AB  - Fourier transform ion cyclotron resonance mass spectrometry has the ability to
      achieve unprecedented mass measurement accuracy (MMA); MMA is one of the most
      significant attributes of mass spectrometric measurements as it affords
      extraordinary molecular specificity. However, due to space-charge effects, the
      achievable MMA significantly depends on the total number of ions trapped in the
      ion cyclotron resonance (ICR) cell for a particular measurement. Even through the
      use of automatic gain control (AGC), the total ion population is not constant
      between spectra. Multiple linear regression calibration in conjunction with AGC
      is utilized in these experiments to formally account for the differences in total
      ion population in the ICR cell between the external calibration spectra and
      experimental spectra. This ability allows for the extension of dynamic range of
      the instrument and for the mean MMA values to remain less than 1 part-per-million
      (ppm). In addition, multiple linear regression calibration is used to account for
      both differences in total ion population in the ICR cell as well as relative ion
      abundance of a given species, which also affords mean MMA values at the parts-per
      billion (ppb) level.

PMID- 17539606
TI  - Human telomere quadruplex: refolding and selection of individual conformers via
      RNA/DNA chimeric editing.
AB  - The conformation of the guanine quadruplex formed by the human telomere (HT)
      repeat in solutions containing physiological concentrations of K+ ions has been a
      topic of intensive investigation during the past several years. Of particular
      interest are the directionality of the overall folding pattern, i.e., parallel,
      antiparallel, or a combination of these two modes, and the alternation, if any,
      of the glycosidic bond conformation between syn and anti. An additional issue
      involves resolving mixtures of conformations when more than one species is
      present. We approach these questions using selective substitution of
      riboguanosine, rG, for deoxyriboguanosine, dG. Using a combination of circular
      dichroism, gel electrophoresis, equilibrium ultracentrifugation, and imino proton
      NMR, we are able to show that these modifications can yield sequences which fold
      into parallel or antiparallel conformations consisting of one or two strands. We
      also demonstrate that chimeric editing of the HT sequence permits isolating one
      of two conformational isomers existing in solution in the presence of KCl. The
      ability to engineer and control quadruplex folding motifs illustrated here with
      HT may prove useful more generally for a variety of quadruplex-forming sequences.

PMID- 17539607
TI  - Probing the promiscuous active site of myo-inositol dehydrogenase using synthetic
      substrates, homology modeling, and active site modification.
AB  - The active site of myo-inositol dehydrogenase (IDH, EC 1.1.1.18) from Bacillus
      subtilis recognizes a variety of mono- and disaccharides, as well as 1l-4-O
      substituted inositol derivatives. It catalyzes the NAD+-dependent oxidation of
      the axial alcohol of these substrates with comparable kinetic constants. We have
      found that 4-O-p-toluenesulfonyl-myo-inositol does not act as a substrate for
      IDH, in contrast to structurally similar compounds such as those bearing
      substituted benzyl substituents in the same position. X-ray crystallographic
      analysis of 4-O-p-toluenesulfonyl-myo-inositol and 4-O-(2-naphthyl)methyl-myo
      inositol, which is a substrate for IDH, shows a distinct difference in the
      preferred conformation of the aryl substituent. Conformational analysis of known
      substrates of IDH suggests that this conformational difference may account for
      the difference in reactivity of 4-O-p-toluenesulfonyl-myo-inositol in the
      presence of IDH. A sequence alignment of IDH with the homologous glucose-fructose
      oxidoreductase allowed the construction of an homology model of inositol
      dehydrogenase, to which NADH and 4-O-benzyl-scyllo-inosose were docked and the
      active site energy minimized. The active site model is consistent with all
      experimental results and suggests that a conserved tyrosine-glycine-tyrosine
      motif forms the hydrophobic pocket adjoining the site of inositol recognition.
      Y233F and Y235F retain activity, while Y233R and Y235R do not. A histidine
      aspartate pair, H176 and D172, are proposed to act as a dyad in which H176 is the
      active site acid/base. The enzyme is inactivated by diethyl pyrocarbonate, and
      the mutants H176A and D172N show a marked loss of activity. Kinetic isotope
      effect experiments with D172N indicate that chemistry is rate-determining for
      this mutant.

PMID- 17539609
TI  - Entropy effects in the fragmentation of 1,1-dimethylhydrazine ions.
AB  - The 1,1-dimethylhydrazine ion ((CH3)2NNH2+*) has two low-energy dissociation
      channels, the loss of a hydrogen atom to form the fragment ion m/z 59,
      (CH3)(CH2)NNH2+, and the loss of a methyl radical to form the fragment ion m/z
      45, the methylhydrazyl cation, CH3NNH2+. The dissociation of the 1,1
      dimethylhydrazine ion has been investigated using threshold photoelectron
      photoion coincidence (TPEPICO) spectroscopy, in the photon energy range 8.25-31
      eV, and tandem mass spectrometry. Theoretical breakdown curves have been obtained
      from a variational transition state theory (VTST) modeling of the two reaction
      channels and compared to those obtained from experiment. Seven transition states
      have been found at the B3-LYP/6-31+G(d) level of theory for the methyl radical
      loss channel in the internal energy range of 2.32-3.56 eV. The methyl loss
      channel transition states are found at R(N-C) = 4.265, 4.065, 3.965, 3.165,
      2.765, 2.665, and 2.565 A over this internal energy range. Three transition
      states have been found for the hydrogen atom loss channel: R(H-C) = 2.298, 2.198,
      and 2.098 A. The DeltaS++(45) value, at an internal energy of 2.32 eV and a bond
      distance of R(N-C) = 4.265 A, is 65 J K-1 mol-1. As the internal energy increases
      to 3.56 eV the variational transition state moves to lower R value so that at R(N
      C) = 2.565 A, the DeltaS++ decreases to 29 J K-1 mol-1. For the hydrogen atom
      loss channel the variation in DeltaS++ is less than that for the methyl loss
      channel. To obtain agreement with the experimental breakdown curves, DeltaS++(59)
      = 26-16 J K-1 mol-1 over the studied internal energy range. The 0 K enthalpies of
      formation (DeltafH0) for the two fragment ions m/z 45 and m/z 59 have been
      calculated from the 0 K activation energies (E0) obtained from the fitting
      procedure: DeltafH0[CH3NNH2+] = 906 +/- 6 kJ mol-1 and DeltafH0[(CH3)(CH2)NNH2+]
      = 822 +/- 7 kJ mol-1. The calculated G3 values are DeltafH0[CH3NNH2+] = 911 kJ
      mol-1 and DeltafH0[(CH3)(CH2)NNH2+] = 825 kJ mol-1. In addition to the two low
      energy dissociation products, 21 other fragment ions have been observed in the
      dissociation of the 1,1-dimethylhydrazine ion as the photon energy was increased.
      Their appearance energies are reported.

PMID- 17539608
TI  - Multiple-frequency EPR spectra of two aqueous Gd3+ polyamino polypyridine
      carboxylate complexes: a study of high field effects.
AB  - In the search for highly efficient magnetic resonance imaging contrast agents,
      polyamino polypyridine carboxylate complexes of Gd3+ have shown unusual
      properties with both very rapid and very slow electron spin relaxation in
      solution observed by electron paramagnetic resonance. Since the relationship
      between the molecular structure and the electron spin properties remains quite
      obscure at this point, detailed studies of such complexes may offer useful clues
      for the design of Gd3+ compounds with tailored electronic features. Furthermore,
      the availability of very high-frequency EPR spectrometers based on quasi-optical
      components provides us with an opportunity to test the existing relaxation
      theories at increasingly high magnetic fields and observation frequencies. We
      present a detailed EPR study of two gadolinium polyamino polypyridine carboxylate
      complexes, [Gd(tpaen)]- and [Gd(bpatcn)(H2O)], in liquid aqueous solutions at
      multiple temperatures and frequencies between 9.5 and 325 GHz. We analyze the
      results using the model of random zero-field splitting modulations through
      Brownian rotation and molecular deformations. We consider the effect of
      concentration on the line width, as well as the possible existence of an
      additional g-tensor modulation relaxation mechanism and its possible impact on
      future experiments. We use (17)O NMR to characterize the water exchange rate on
      [Gd(bpatcn)(H2O)] and find it to be slow (approximately 0.6 x 10(6) s-1).

PMID- 17539610
TI  - Ab initio chemical kinetics for the OH+HNCN reaction.
AB  - The kinetics and mechanism of the reaction of the cyanomidyl radical (HNCN) with
      the hydroxyl radical (OH) have been investigated by ab initio calculations with
      rate constants prediction. The single and triplet potential energy surfaces of
      this reaction have been calculated by single-point calculations at the CCSD(T)/6
      311+G(3df,2p) level based on geometries optimized at the B3LYP/6-311+G(3df,2p)
      and CCSD/6-311++G(d,p) levels. The rate constants for various product channels in
      the temperature range of 300-3000 K are predicted by variational transition-state
      and Rice-Ramsperger-Kassel-Marcus (RRKM) theories. The predicted total rate
      constants can be represented by the expressions ktotal=2.66 x 10(+2)xT-4.50 exp(
      239/T) in which T=300-1000 K and 1.38x10(-20)xT2.78 exp(1578/T) cm3 molecule(-1)
      s(-1) where T=1000-3000 K. The branching ratios of primary channels are
      predicted: k1 for forming singlet HON(H)CN accounts for 0.32-0.28, and k4 for
      forming singlet HONCNH accounts for 0.68-0.17 in the temperature range of 300-800
      K. k2+k7 for producing H2O+NCN accounts for 0.55-0.99 in the high-temperature
      range of 800-3000 K. The branching ratios of k3 for producing HCN+HNO, k6 for
      producing H2N+NCO, k8 for forming 3HN(OH)CN, k9 for producing CNOH+3NH, and
      k5+k10 for producing NH2+NCO are negligible. The rate constants for key
      individual product channels are provided in a table for different temperature and
      pressure conditions.

PMID- 17539611
TI  - "Effective" negative surface tension: a property of coated nanoaerosols relevant
      to the atmosphere.
AB  - Atmospheric aerosols play a very important role in atmospheric processes and have
      a major influence on the global climate. In this paper, we report results of a
      molecular dynamics study on the unique properties of organic-coated water
      droplets. In particular, we find that, for particles preferring an inverted
      micelle structure, the lower chain-chain interaction, with increasing radial
      distance from the water-organic interface, results in a negative internal radial
      pressure profile for the organic layer. As a result, a coated particle behaves as
      though the surface tension is "negative" and implies that such a particle will
      inherently have an inverse Kelvin vapor pressure effect, resulting in increased
      water condensation.

PMID- 17539612
TI  - Vibrational corrections to magneto-optical rotation: a computational study.
AB  - Vibrational corrections to the Verdet constants of nine molecules (H2, N2, CO,
      H2O, CH4, benzene, toluene, p-xylene, and o-xylene) were calculated with pure
      density functional theory (DFT), hybrid DFT, and an approximate coupled-cluster
      theory. Comparisons are made for the accuracy of the vibrational averages among
      different methods and with respect to experimental data where available. It is
      found that vibrational corrections to magneto-optical rotation can be as large as
      10% of the equilibrium value. Hybrid DFT with the B3LYP hybrid functional offers
      reasonable accuracy at a relatively inexpensive computational cost for accurate
      calculations of vibrationally averaged Verdet constants.

PMID- 17539613
TI  - Tautomerism phenomenon of pyrazolo[3,4-b]quinoline: spectroscopic and quantum
      mechanical studies.
AB  - Tautomerism of pyrazolo[3,4-b]quinoline (PQ) was studied using electronic
      absorption and emission spectroscopies in various polar and nonpolar solvents.
      The absorption spectra of the tautomers were modeled, and the respective bands
      were assigned using ab initio quantum mechanical calculations. Temperature
      dependent absorption spectra showed the dynamic equilibrium of the two species,
      which were observed only in aliphatic solvents. The anomalous relative
      populations of the tautomers were explained by the stabilizing effect of the
      specific PQ-hydrocarbon interactions. Excited-state intramolecular proton
      transfer (ESIPT) was proposed to explain the measured fluorescence spectra.
      Hydrogen bonds that are formed in methanol and benzene were shown to strongly
      influence the nature of both the absorption and emission spectra.

PMID- 17539614
TI  - Vibrational overtone spectroscopy of three-membered rings.
AB  - We have recorded vapor-phase photoacoustic spectra of cyclopropane, ethylene
      oxide, and ethylene sulfide in the third, fourth, and fifth CH-stretching
      overtone regions. We have used a harmonically coupled anharmonic oscillator local
      mode model to facilitate analysis of the spectra. Fermi resonance between the CH
      stretching and HCH-bending vibrations is essential to explain the observed wide
      and multistructured CH-stretching overtone bands. A number of weak combination
      bands can account for the remaining experimental features observed to the blue of
      the CH-stretching regions. We have reassigned the fundamental spectra of these
      three-membered rings.

PMID- 17539615
TI  - Nucleophilicity of indole derivatives: activating and deactivating effects based
      on proton affinities and electron density properties.
AB  - Activating and deactivating abilities of several substituents (-CH3, -F, -NH2, 
      NO2) in indole have been theoretically studied using a series of electron density
      based reactivity indices. Calculations have been performed at the B3LYP/6
      311++G(2d,2p) level. An energetic criterion based on the proton affinities (PAs)
      has been employed to check the validity of these reactivity indices. Relative PAs
      reflect the ortho and para orientation ability of -CH3, -F, and -NH2 groups,
      whereas the large deactivating effect of -NO2 is mainly observed at these
      positions. Also, substitutions in carbons 2 and 6 (IUPAC nomenclature)
      activate/deactivate carbons 6 and 2, respectively. Inductive effects are also
      reflected on the values of the relative PAs. The -CH3 group is shown to have
      inductive electron-withdrawing character instead of electron-releasing with its
      activating ability being due to a small mesomeric electron-releasing character.
      pi atomic electron populations and the zz component of the atomic quadrupole
      electric tensor qualitatively explain the order of PAs. Fukui indices
      approximately predict the results obtained by the previous properties, whereas no
      correlation is found between the values of the (triangle down)2rho(r) at the
      secondary charge concentrations and the PA scale.

PMID- 17539616
TI  - Complexes with N-H(+)-P hydrogen bonds: structures, binding energies, and spin
      spin coupling constants.
AB  - Ab-initio MP2/aug'-cc-pVTZ calculations have been performed to determine the
      structures and binding energies of proton-bound complexes stabilized by N-H+-P
      hydrogen bonds and to investigate the nature of the proton-transfer coordinate in
      these systems. Double minima are found only when the difference between the
      protonation energies of the N and P bases is less than about 4 kcal/mol. The
      isomer in which the protonated nitrogen base is the donor lies lower on the
      potential surface and also has a greater binding energy relative to the
      corresponding isolated monomers. Equation-of-motion coupled cluster singles and
      doubles (EOM-CCSD) calculations have been employed to obtain one- and two-bond
      spin-spin coupling constants across these hydrogen bonds. Two-bond coupling
      constants (2h)J(N-P) correlate with N-P distances, irrespective of whether the
      donor ion is N-H+ or P-H+. One-bond coupling constants (1)J(N-H) and (1h)J(H-P)
      for complexes stabilized by N-H+...P hydrogen bonds correlate with corresponding
      distances, but similar correlations are not found for (1)J(P-H) and (1h)J(H-N)
      for complexes with P-H+...N hydrogen bonds. Negative values of (1h)K(H-N) and
      (1h)K(H-P) indicate that the hydrogen bonds in these complexes are traditional.
      Comparisons are made with complexes stabilized by N-H+-N and P-H+-P hydrogen
      bonds.

PMID- 17539617
TI  - A two transition state model for radical-molecule reactions: applications to
      isomeric branching in the OH-isoprene reaction.
AB  - A two transition state model is applied to the prediction of the isomeric
      branching in the addition of hydroxyl radical to isoprene. The outer transition
      state is treated with phase space theory fitted to long-range transition state
      theory calculations on an electrostatic potential energy surface. High-level
      quantum chemical estimates are applied to the treatment of the inner transition
      state. A one-dimensional master equation based on an analytic reduction from two
      dimensions for a particular statistical assumption about the rotational part of
      the energy transfer kernel is employed in the calculation of the pressure
      dependence of the addition process. We find that an accurate treatment of the two
      separate transition state regions, at the energy and angular momentum resolved
      level, is essential to the prediction of the temperature dependence of the
      addition rate. The transition from a dominant outer transition state to a
      dominant inner transition state is shown to occur at about 275 K, with
      significant effects from both transition states over the 30-500 K temperature
      range. Modest adjustments in the ab initio predicted inner saddle point energies
      yield predictions that are in quantitative agreement with the available high
      pressure limit experimental observations and qualitative agreement with those in
      the falloff regime. The theoretically predicted capture rate is reproduced to
      within 10% by the expression [1.71 x 10(-10)(T/298)(-2.58) exp(-608.6/RT) + 5.47
      x 10(-11)(T/298)-1.78 exp(-97.3/RT); with R = 1.987 and T in K] cm3 molecule(-1)
      s(-1) over the 30-500 K range. A 300 K branching ratio of 0.67:0.02:0.02:0.29 was
      determined for formation of the four possible OH-isoprene adduct isomers 1, 2, 3,
      and 4, respectively, and was found to be relatively insensitive to temperature.
      An Arrhenius activation energy of -0.77 kcal/mol was determined for the high
      pressure addition rate constants around 300 K.

PMID- 17539618
TI  - Density functional studies on the effects of hydrogen bonding on the formation of
      a charge-transfer complex between p-benzoquinone and 2,6-dimethoxyphenol.
AB  - The ability to form a ground-state charge-transfer (CT) complex between an
      electron acceptor, p-benzoquinone (BQ) and an electron donor, 2,6-dimethoxyphenol
      (DMOPh) was found to be enhanced by H-bonding of BQ to a hydrogen-bond donor,
      trifluoroacetic acid (TFA) and H-bonding DMOPh to a hydrogen-bond acceptor, 4
      (N,N-dimethylamino)pyridine (DMAPy) [Chem. Phys. Lett. 2005, 401, 200]. Here is
      reported density functional theory (DFT) calculations to study the effect of H
      bonding to electron donor and electron acceptor moieties on the ground-state CT
      complex formation ability between the aforementioned electron donor/acceptor
      pair. DFT calculations using B3LYP with the 6-311G(d,p) basis set show that the
      HOMO and LUMO energies of BQ drop on H-bonding to TFA through its C=O groups and
      the HOMO and LUMO energies of DMOPh increase on H-bonding to DMAPy via its O-H
      group. BQ molecules hydrogen-bonded as 1:1 and 1:2 complexes to TFA act as
      stronger acceptors than the bare molecule, while 1:1 complexes of DMOPh and DMAPy
      act as better donors. Vertical excitation energies for electronic transitions
      from the ground state to the first few excited states of BQ, DMOPh, DMAPy, and
      their different complexes have been investigated in the framework of time
      dependent density functional theory (TD-DFT) to simulate and interpret
      experimental ultraviolet absorption spectra. Good agreement between experimental
      and calculated spectra is established. The enhancement of the CT complex
      formation ability between the BQ and DMOPh pair is favored by the strong H
      bonding interaction of BQ with TFA as well as by the H-bonding interaction of
      DMOPh with DMAPy.

PMID- 17539619
TI  - Theoretical investigation of the excited states of coumarin dyes for dye
      sensitized solar cells.
AB  - Using time-dependent density functional theory (TD-DFT), configuration
      interaction single (CIS) method, and approximate coupled cluster singles and
      doubles (CC2) method, we investigated the absorption spectra of coumarin
      derivative dyes (C343, NKX-2388, NKX-2311, NKX-2586, and NKX-2677), which have
      been synthesized for efficient dye-sensitized solar cells. The CC2 calculations
      are found in good agreement with the experimental results except for the smallest
      coumarin dye (C343). TD-DFT underestimates the vertical excitation energy of the
      larger coumarin dyes (NKX-2586 and -2677). Solvents (methanol) are found to
      induce a red shift of the vertical excitation energies, and their effects on the
      molecular geometry and the electronic structure are examined in detail. The
      deprotonated form of coumarin is also investigated, where a blue shift of the
      vertical excitation energies is observed.

PMID- 17539620
TI  - Novel ergopeptides as dual ligands for adenosine and dopamine receptors.
AB  - Multivalent ligands are promising pharmacological tools that may be more
      efficacious for several diseases than highly selective single-target drugs. A
      combined therapy using dopaminergic agonists and adenosinergic antagonists is
      currently being evaluated for the treatment of Parkinson's disease. [(a) Kanda,
      T.; et al. Exp. Neurol. 2000, 162, 321-327. (b) Jenner, P. Expert Opin. Invest.
      Drugs 2005, 14, 729-738. (c) Kase, H.; et al. Neurology 2003, 61 (Suppl 6), S97
      S100.] Here we prepared dual ligands acting on adenosine and dopamine receptors
      by applying a combinatorial approach based on the ergolene privileged structure.
      The potency and efficacy of these novel compounds were determined by radioligand
      binding studies and intracellular cAMP production assays in cells expressing
      adenosine and dopamine receptors. Selected compounds displayed dual dopamine
      agonist and adenosine antagonist activity. Molecules with this pharmacological
      profile are potentially useful for studying dopamine-adenosine cross-talk in the
      central nervous system and for testing the therapeutic potential of multivalent
      drugs for Parkinson's disease.

PMID- 17539621
TI  - Synthesis of stable and potent delta/mu opioid peptides: analogues of H-Tyr-c[D
      Cys-Gly-Phe-D-Cys]-OH by ring-closing metathesis.
AB  - Ring-closing metathesis has emerged as a powerful tool in organic synthesis for
      generating cyclic structures via C-C double bond formation. Recently, it has been
      successfully used in peptide chemistry for obtaining cyclic molecules bridged
      through an olefin unit in place of the usual disulfide bond. Here, we describe
      this approach for obtaining cyclic olefin bridged analogues of H-Tyr-c[D-Cys-Gly
      Phe-Cys]-OH. The synthesis of the new ligands was performed using the second
      generation Grubbs' catalyst. The resulting cis-8 (cDADAE) and trans-9 (tDADAE)
      were fully characterized and tested at delta, mu, and kappa opioid receptors.
      Also the linear precursor 13 (lDADAE) and the hydrogenated derivative 11 (rDADAE)
      also were tested. All the cyclic products containing a olefinic bond are slightly
      selective but highly active and potent for the delta and mu opioid receptors.
      Activity toward the kappa opioid receptors was absent or very low.

PMID- 17539622
TI  - Novel C-6 fluorinated acyclic side chain pyrimidine derivatives: synthesis, (1)H
      and (13)C NMR conformational studies, and antiviral and cytostatic evaluations.
AB  - The synthetic route for introduction of a fluoroalkyl (7-12, 14), fluoroalkenyl
      (15 and 16), fluorophenylalkyl (17, 19, 20, and 22), and fluorophenylalkenyl (18,
      21) side chain at C-6 of the pyrimidine involved the lithiation of the pyrimidine
      derivatives 3 and 3a and subsequent nucleophilic addition or substitution
      reactions of the organolithium intermediate thus obtained with various
      electrophiles. Conformational properties of the novel fluorinated pyrimidine
      derivatives were assessed by the use of 1D difference NOE enhancements and C-F
      coupling constants. Compounds 4-22 were evaluated for their antiviral and
      cytostatic activities. Of all compounds evaluated, the 5-bromopyrimidine
      derivatives 5 and 6 showed the highest inhibitory activities. Among the series of
      fluoroalkylated pyrimidines, which is generally more active than the series of
      fluorophenylalkylated pyrimidines, compounds 8 and 14 displayed moderate
      cytostatic activities against the tested tumor cell lines. Moreover, compound 8
      containing a 2-fluoromethylpropyl side chain expressed some but not highly
      specific activity against varicella-zoster virus (VZV). From C-6
      fluorophenylalkylated pyrimidine derivatives, 17a and 21 showed a slight activity
      against cytomegalovirus (CMV), VZV, and Coxsackie B4 virus, respectively.
      Besides, compounds 17a and 21 showed no cytotoxic effect.

PMID- 17539623
TI  - Functional differences in epigenetic modulators-superiority of mercaptoacetamide
      based histone deacetylase inhibitors relative to hydroxamates in cortical neuron
      neuroprotection studies.
AB  - We compare the ability of two structurally different classes of epigenetic
      modulators, namely, histone deacetylase (HDAC) inhibitors containing either a
      hydroxamate or a mercaptoacetamide as the zinc binding group, to protect cortical
      neurons in culture from oxidative stress-induced death. This study reveals that
      some of the mercaptoacetamide-based HDAC inhibitors are fully protective, whereas
      the hydroxamates show toxicity at higher concentrations. Our present results
      appear to be consistent with the possibility that the mercaptoacetamide-based
      HDAC inhibitors interact with a different subset of the HDAC isozymes [less
      activity at HDAC1 and 2 correlates with less inhibitor toxicity], or
      alternatively, are interacting selectively with only the cytoplasmic HDACs that
      are crucial for protection from oxidative stress.

PMID- 17539624
TI  - Exploring peptide-likeness of active molecules using 2D fingerprint methods.
AB  - Similarity searching for peptide-like small molecules is a difficult task because
      the amide backbone shared by these molecules tends to mask features that
      determine biological activity. We have investigated 2D fingerprints for their
      ability to differentiate between peptide-like molecules having different activity
      or to facilitate a peptidomimetic transition from molecules with strong peptide
      character to compounds having little or none. For these purposes, different
      compound activity classes were assembled consisting of molecules having strong,
      moderate, and weak peptide character. For the quantification of peptide
      character, a "peptide flavor" index was introduced. In systematic search
      calculations, an encouraging finding has been that most of the investigated 2D
      fingerprints were capable of distinguishing between peptide-like molecules having
      different activities. However, only two fingerprints of different design also
      displayed a strong tendency to detect molecules with decreasing peptide
      character. One of these search tools is a recently introduced property descriptor
      based fingerprint that showed two additional advantages: its flexible design
      could be adjusted to increasingly recover molecules with little peptide-likeness,
      and in addition, its search performance was not affected by differences in
      molecular size.

PMID- 17539626
TI  - Electronic ground state and the d-d transitions in bis(biuretato)cobaltate(III)
      ions.
AB  - The electronic structure of a class of compounds based on the
      bis(biuretato)cobaltate(III) ion has been investigated by spectroscopic methods
      (UV-vis, CD, MCD), magnetic susceptibility, and ligand field theory. The concept
      of molecules in molecules has been introduced to account for the conjugated pi
      system of the whole ligand entity and its perturbation of the metal ion 3d
      orbitals. The Slater-Condon-Racah scheme was fully exploited; in particular,
      differences in occupation numbers of the spin orbitals have been used in the
      spectral assignments of the d-d transitions. The energy calculations used one
      sigma parameter, two pi parameters, and two Racah parameters. The pi parameters,
      which were derived from Orgel orbitals of chi and psi type, were found to be
      positive. The observed charge-transfer transitions are metal <-- ligand. The
      results of our calculations are in agreement with available experimental data,
      including the spin triplet ground state and the position of the lower d-d
      transitions. The approach is general and, for example, applicable to heme
      iron(II).

PMID- 17539627
TI  - Synthesis and antimicrobial activities of isomers of N(4),N(11)-dimethyl
      3,5,7,7,10,12,14,14-octamethyl-1,4,8,11-tetraazacyclotetradecane and their
      nickel(II) complexes.
AB  - The reactions of two isomers of 3,5,7,7,10,12,14,14-octamethyl-1,4,8,11
      tetraazacyclotetradecane (differing in the orientation of the methyl groups on
      the chiral carbon atoms), designated as L(B) and L(C), with CH(3)I in the ratio
      of 1:4 resulted in the substitution of the N(4) and N(11) protons by CH(3)
      groups, forming the dimethyl derivatives L(BZ) and L(CZ), respectively. These
      ligands, on interaction with nickel(II) acetate tetrahydrate and subsequent
      addition of lithium perchlorate, produce square-planar yellow
      [NiL(BZ)][ClO(4)](2) and orange [NiL(C'Z)][ClO(4)](2). These nickel complexes
      undergo axial ligand addition reactions with NCS(-), Cl(-), Br(-), and I(-) as X(
      ) to form six-coordinate trans-diisothiocyanato, -dichloro, -dibromo, and -diiodo
      complexes of formula [NiLX(2)], where L = L(BZ) or L(C'Z), and X = SCN, Cl, Br,
      or I. All these compounds have been characterized on the basis of analytical,
      spectroscopic, conductometric, and magnetochemical data. The structures of L(BZ)
      and two variants of [Ni"L(BZ)"][ClO(4)](2) (crystallizing in the space group
      P2(1)/n and Pn, respectively; "L(BZ)" symbolizes partially methylated ligand)
      have been determined by single-crystal X-ray analyses. The antifungal and
      antibacterial activities of these compounds have been studied against some
      phytopathogenic fungi and bacteria.

PMID- 17539628
TI  - Phenolate- and acetate (both mu(2)-1,1 and mu(2)-1,3 mode)-bridged face-shared
      trioctahedral linear Ni(II)(3), Ni(II)(2)M(II) (M = Mn, Co) complexes: ferro- and
      antiferromagnetic coupling.
AB  - The complexes [(L)(2)Ni(II)(2)M(II)(mu(2)-1,3-OAc)(2)(mu(2)-1,1-OAc)(2)(S)(2)] x
      xMeOH [HL = N-methyl-N-(2-hydroxybenzyl)-2-aminoethyl-2-pyridine; M = Ni, S =
      MeOH, x = 6 (1); M = Mn, S = H(2)O, x = 0 (2); M = Co, S = MeOH, x = 6 (3)] have
      been synthesized. Crystal structures reveal that three octahedral MII ions form a
      linear array with two terminal moieties {(L)Ni(II)(mu(2)-1,3-OAc)(mu(2)-1,1
      OAc)(MeOH/H(2)O)}(-) in a facial donor set and a central MII ion which is
      connected to the terminal ions via bridging phenolate and two types of bridging
      acetates. Magnetic measurements reveal that the Ni(II)(3) and Ni(II)(2)Co(II)
      centers are ferromagnetically and Ni(II)(2)Mn(II) center is antiferromagnetically
      coupled. An attempt has been made to rationalize the observed magneto-structural
      behavior.

PMID- 17539629
TI  - Synthesis and structural studies of NCN diimine palladium pincer complexes
      bearing m-terphenyl scaffolds.
AB  - The reaction of 2,6-[2-{RN=C(H)}C(6)H(4)](2)C(6)H(3)I [R = Ph (4), Cy (5), 2,6
      Me(2)C(6)H(3) (6), 2,4,6-Me(3)C(6)H(2) (7), (S)-alpha-methylbenzyl (8)] with
      Pd(2)(dba)(3) afforded the NCN diimine pincer palladium complexes [2,6-[2
      {RN=C(H)}C(6)H(4)](2)C(6)H(3)PdI] (9-13) by oxidative addition of the C-I bonds
      of the ligand precursors. Single-crystal X-ray diffraction analyses of complexes
      9-13 reveal formal C(2)-symmetric environments. Variable-temperature NMR studies
      of complexes 11 and 12 show hindered rotation about the N-Ar bonds and also
      suggest that atropisomers of complexes 9-13 do not interconvert on the NMR time
      scale. Consistent with this proposal, isolation of the two possible isomers of 13
      (13a and 13b) was possible, and their structures and NMR properties have been
      examined in detail.

PMID- 17539630
TI  - Structural characterization and NMR study of NaNbWO(6) and its proton-exchanged
      derivatives.
AB  - The structural characterization of NaNbWO(6), prepared by the ceramic route, has
      been performed. Electron diffraction has shown the presence of two related phases
      in a 1:1 ratio, whose lattice parameters correspond to those of the well-known
      tetragonal tungsten bronzes (TTB) and those of a monoclinically distorted phase.
      In addition to basic unit cells, the morphology of the two phases has been found
      to be similar, but they present a slight difference in the W/Nb ratio. (1)H and
      (23)Na magic-angle spinning nuclear magnetic resonance (MAS-NMR) spectra of
      NaNbWO(6) and its proton-exchanged derivatives have been interpreted on the basis
      of the ideal TTB structure. The average structure and the morphology remain
      unchanged in Na(1-x)H(x)NbWO(6) derivatives. (1)H and (23)Na MAS-NMR
      spectroscopies have been used to monitor changes produced during exchange
      processes. It has been shown that the exchange of Na ions is mainly produced, but
      not exclusively, at tetragonal channels. However, a large amount of Na ions at
      the pentagonal channels do not exchange with protons, suggesting that these ions
      are needed to stabilize the TTB-like structure. A tentative distribution of
      sodium ions in the most-exchanged oxide, deduced from NMR results, approximately
      (Na(0.46))(p)(Na(0.08))(s)H(0.46)NbWO(6), has been proposed. NMR spectra of Na(1
      x)H(x)NbWO(6) indicate that two different OH groups are formed upon exchanging.
      The study of samples hydrated with D(2)O allowed us to conclude that deuterons of
      adsorbed water exchange with protons of the two OH groups. The proton-deuteron
      exchange is slow at room temperature but is strongly enhanced at 90 degrees C.
      This observation relates to the proton conductivity displayed by exchanged
      products under a humid atmosphere.

PMID- 17539631
TI  - Synthesis and characterization of four metal-organophosphonates with one-, two-,
      and three-dimensional structures.
AB  - A series of metal-organic hybrid compounds were synthesized using two new
      phosphonic acids, pyridyl-4-phosphonic acid and p-xylylenediphosphonic acid
      (H(2)O(3)PCH(2)C(6)H(4)CH(2)PO(3)H(2)). The phosphonic acid ligands have been
      synthesized from their corresponding bromides following two different types of
      reactions. The reaction of pyridyl-4-phosphonic acid with three different
      divalent metal salts results in the formation of molecular structures of
      different dimensionality. The reaction of Cu(II) with the phosphonic acid under
      hydrothermal conditions yields a three-dimensional (3D) open framework structure
      having the molecular formula [Cu(4)(NC(5)H(4)-PO(3))(4)(H(2)O)(10)] (1). The
      reactions with Mn(II) and Zn(II) salts with the same phosphonic acid resulted in
      a two-dimensional layered and a dinuclear compound with molecular formulas
      [Mn(3)(NC(5)H(4)-PO(3))(4)(H(2)O)(6)(ClO(4))(2)] (2) and [Zn(2)(NHC(5)H(4)
      PO(3)H)(2)Cl(4)] (3), respectively. Compound 1 crystallizes in the triclinic
      crystal system having space group P with structural parameters a = 7.4564(15)
      Angstrom, b = 9.1845(19) Angstrom, c = 11.582(2) Angstrom, alpha = 100.842(3)
      degrees, beta = 104.303(3) degrees, gamma = 94.774(3) degrees, and Z = 1.
      Compound 2 crystallizes in the triclinic crystal system, space group P, with
      structural parameters a = 7.6871(14) Angstrom, b = 10.576(2) Angstrom, c =
      14.470(3)Angstrom, alpha = 81.340(3) degrees, beta = 81.561(3) degrees, gamma =
      68.757(3) degrees, and Z = 2, whereas compound 3 crystallizes in a monoclinic
      crystal system with space group P2(1)/n. The structural parameters are as
      follows: a = 8.4969 (5) Angstrom, b = 9.3911 (5) Angstrom, c = 12.3779 (6)
      Angstrom, beta = 90.860(17) degrees, and Z = 4. The pyridylphosphonate ligand
      shows different ligation behavior toward the three divalent metal ions. On the
      other hand, p-xylylenediphosphonic acid on reaction with Co(II) formed a 3D
      compound [Co(2)(O(3)PCH(2)C(6)H(4)CH(2)PO(3))(2)(H(2)O)(2)] (4) with a layered
      and pillared structure. Compound 4 crystallizes in an orthorhombic crystal system
      with space group Pnma. The structural parameters are a = 21.744(4) Angstrom, b =
      5.6744(10) Angstrom, c = 4.7927(9) Angstrom, and Z = 4.

PMID- 17539633
TI  - Table salt and other alkali metal chloride oligomers: structure, stability, and
      bonding.
AB  - We have investigated table salt and other alkali metal chloride monomers, ClM,
      and (distorted) cubic tetramers, (ClM)(4), with M = Li, Na, K, and Rb, using
      density functional theory (DFT) at the BP86/TZ2P level. Our objectives are to
      determine how the structure and thermochemistry (e.g., Cl-M bond lengths and
      strengths, oligomerization energies, etc.) of alkali metal chlorides depend on
      the metal atom and to understand the emerging trends in terms of quantitative
      Kohn-Sham molecular orbital (KS-MO) theory. The analyses confirm the high
      polarity of the Cl-M bond (dipole moment, VDD, and Hirshfeld atomic charges).
      They also reveal that bond overlap derived stabilization (approximately -26, -20,
      and -8 kcal/mol), although clearly larger than in the corresponding F-M bonds,
      contributes relatively little to the (trend in) bond strengths (-105, -90, and 
      94 kcal/mol) along M = Li, Na, and K. Thus, the Cl-M bonding mechanism resembles
      more closely that of the even more ionic F-M bond than that of the more covalent
      C-M or H-M bonds. Tetramerization causes the Cl-M bond to expand, and it reduces
      its polarity.

PMID- 17539632
TI  - Potentiometric and relaxometric properties of a gadolinium-based MRI contrast
      agent for sensing tissue pH.
AB  - The pH-sensitive contrast agent, GdDOTA-4AmP (Gd1) has been successfully used to
      map tissue pH by MRI. Further studies now demonstrate that two distinct chemical
      forms of the complex can be prepared depending upon the pH at which Gd(3+) is
      mixed with ligand 1. The desired pH-sensitive form of this complex, referred to
      here as a Type II complex, is obtained as the exclusive product only when the
      complexation reaction is performed above pH 8. At lower pH values, a second
      complex is formed that, by analogy with an intermediate formed during the
      preparation of GdDOTA, we tentatively assign to a Type I complex where the Gd(3+)
      is coordinated only by the appended side-chain arms of 1. The proportion of Type
      I complex formed is largely determined by the pH of the complexation reaction.
      The magnitude of the pH-dependent change in the relaxivity of Gd1 was found to be
      less than earlier reported (Zhang, S.; Wu, K.; Sherry, A. D. Angew. Chem., Int.
      Ed. 1999, 38, 3192), likely due to contamination of the earlier sample by an
      unknown amount of Type I complex. Examination of the nuclear magnetic relaxation
      dispersion and relaxivity temperature profiles, coupled with information from
      potentiometric titrations, shows that the amphoteric character of the phosphonate
      side chains enables rapid prototropic exchange between the single bound water of
      the complex with the bulk water thereby giving Gd1 a unique pH-dependent
      relaxivity that is quite useful for the pH mapping of tissues by MRI.

PMID- 17539634
TI  - Preparation and characterization of lithium imidoalanate complexes
      Li(2)[(RN)(4)(AlH(2))(6)] (R = Me or (t)()Bu): first examples of aluminum-rich
      imidoalanes with an adamantoid structure.
AB  - Whereas methylammonium chloride, [MeNH(3)]Cl, reacts with LiGaH(4) in an ether
      solution to give, according to the conditions, either the adduct MeH(2)N x GaH(3)
      or the cationic derivative [(MeH(2)N)(2)GaH(2)](+)Cl(-), the corresponding
      reaction of [MeNH(3)]Cl or [(t)BuNH(3)]Cl with LiAlH(4) proceeds mainly, with
      H(2) elimination, to the imidoalane Li(2)[(RN)(4)(AlH(2))(6)] (R = Me, 1, or
      (t)Bu, 2). The crystal structure of 1 x 2Et(2)O reveals, for the first time,
      anionic units with an adamantane-like Al(6)N(4) skeleton. The Li cations exist at
      two distinct sites, each linked via Li(mu-H)Al bridges to two
      [(MeN)(4)(AlH(2))(6)](2-) cages. Despite disordering of the tBu groups, the
      crystal structure of 2 evidently includes analogous anionic units. By contrast,
      the main product of the reaction between [(i)PrNH(3)]Cl and LiAlH(4) under
      similar conditions is the known neutral, hexameric imidoalane [(i)PrNAlH](6), 3,
      the crystal structure of which has been redetermined.

PMID- 17539635
TI  - Vibrational spectroscopy reveals electrostatic and electrochemical doping in
      organic thin film transistors gated with a polymer electrolyte dielectric.
AB  - We apply attenuated total internal reflection Fourier transform infrared (ATR
      FTIR) spectroscopy to directly probe active layers in organic thin film
      transistors (OTFTs). The OTFT studied uses the n-type organic semiconductor N-N'
      dioctyl-3,4,9,10-perylene tetracarboxylic diimide (PTCDI-C8) and a polymer
      electrolyte gate dielectric made from poly(ethylene oxide) and LiClO4. FTIR
      spectroscopy of the device shows signatures of anionic PTCDI-C8 species and broad
      polaron bands when the organic semiconductor layer is doped under positive gate
      bias (VG). There are two distinctive doping regions: a reversible and
      electrostatic doping region for VG <or= 2 V and an irreversible and
      electrochemical doping regime for VG>2 V. On the basis of intensity loss of
      vibrational peaks attributed to neutral PTCDI-C8, we obtain a charge carrier
      density of 2.9 x 10(14)/cm2 at VG=2 V; this charge injection density corresponds
      to the conversion of slightly more than one monolayer of PTCDI-C8 molecules into
      anions. At higher gate bias voltage, electrochemical doping involving the
      intercalation of Li+ into the organic semiconductor film can convert all PTCDI-C8
      molecules in a 30-nm film into anionic species. For comparison, when a
      conventional gate dielectric (polystyrene) is used, the maximum charge carrier
      density achievable at VG=200 V is approximately 4.5 x 10(13)/cm2, which
      corresponds to the conversion of 18% of a monolayer of PTCDI-C8 molecules into
      anions.

PMID- 17539636
TI  - Inhibitor fingerprinting of matrix metalloproteases using a combinatorial peptide
      hydroxamate library.
AB  - We report the inhibitor fingerprints of seven matrix metalloproteases,
      representing all five established families of this important class of enzymes,
      against a highly diversified small-molecule library. A total of 1400 peptide
      hydroxamates were individually prepared by systematically permuting both natural
      and unnatural amino acids across the P1', P2', and P3' positions, thereby
      generating an inhibitor library with three-pronged structural diversity. High
      throughput screenings were efficiently conducted in microtiter plate format,
      providing a rapid and quantitative determination of inhibitor potency across the
      panel of enzymes. Despite similarities in substrate preferences and structural
      homologies within this class of enzymes, our findings revealed distinct patterns
      of inhibition for each MMP against varied chemical scaffolds. The resulting
      inhibitor fingerprints readily facilitated the identification of inhibitors with
      good potency as well as desirable selectivity, potentially minimizing adverse
      effects when developing such leads into candidate drugs. The strategy also offers
      a novel method for the functional classification of matrix metalloproteases, on
      the basis of the characteristic profiles obtained using the diverse set of
      inhibitors. This approach thus paves the way forward in lead identification by
      providing a rapid and quantitative method for selectivity screening at the outset
      of the drug discovery process.

PMID- 17539637
TI  - Highly regio-, diastereo-, and enantioselective Pd-catalyzed allylic alkylation
      of acyclic ketone enolates with monosubstituted allyl substrates.

PMID- 17539638
TI  - Determining the helical tilt angle of a transmembrane helix in mechanically
      aligned lipid bilayers using EPR spectroscopy.

PMID- 17539639
TI  - Reversible interconversion of homochiral triangular macrocycles and helical
      coordination polymers.

PMID- 17539641
TI  - Ruthenium-catalyzed [2 + 2 + 2] cocyclization of diene-yne.

PMID- 17539640
TI  - Characterization of NcsB2 as a promiscuous naphthoic acid/coenzyme A ligase
      integral to the biosynthesis of the enediyne antitumor antibiotic
      neocarzinostatin.

PMID- 17539642
TI  - Mesoporous carbon single-crystals from organic-organic self-assembly.

PMID- 17539643
TI  - Remarkable loop flexibility in avian influenza N1 and its implications for
      antiviral drug design.

PMID- 17539644
TI  - Photochemically induced autocatalysis in the chlorate ion-iodine system.

PMID- 17539645
TI  - Chemically patterned microspheres for controlled nanoparticle assembly in the
      construction of SERS hot spots.

PMID- 17539646
TI  - Direct palladium-catalyzed alkynylation of N-fused heterocycles.

PMID- 17539647
TI  - Synthesis of pyrrolo-isoquinolines related to the lamellarins using silver
      catalyzed cycloisomerization/dipolar cycloaddition.

PMID- 17539650
TI  - Rearrangement of propargylic esters: metal-based stereospecific synthesis of (E)-
      and (Z)-knoevenagel derivatives.

PMID- 17539649
TI  - Palladium-catalyzed direct functionalization of imidazolinone: synthesis of
      dibromophakellstatin.

PMID- 17539652
TI  - Lactol-directed osmylation. Stereodivergent synthesis of four C-19,20 apoptolidin
      diols from a single allylic hemiacetal.
AB  - A synthetic approach to prepare four Apoptolidin C-19,20 diastereomeric diol
      derivatives was developed. Two diastereomers were obtained from the (Z)-form,
      which is converted to the (E)-form, followed by dihydroxylation to deliver two
      more diastereomers. The (E)-allylic hemiacetal and methoxyacetal showed opposite
      diastereoselectivity.

PMID- 17539653
TI  - An efficient method to depolymerize polyamide plastics: a new use of ionic
      liquids.
AB  - Treatment of polyamides in an ionic liquid at 300 degrees C resulted in the
      efficient depolymerization of polyamides to give corresponding monomeric lactam
      in good yields. The recovered monomer was collected by direct distillation of the
      reaction mixture. PP13 TFSI furnished the best results for the depolymerization.
      The ionic liquid could be recycled five times in the present reaction.

PMID- 17539654
TI  - Daphlongeranines A and B, two novel alkaloids possessing unprecedented skeletons
      from Daphniphyllum longeracemosum.
AB  - Two novel alkaloids, daphlongeranines A (1) and B (2), with an unprecedented ring
      system, were isolated from the fruits of Daphniphyllum longeracemosum. Their
      unique structures and relative stereochemistries were established on the basis of
      spectroscopic and single-crystal diffraction analysis. The proposed biosynthetic
      pathway was also discussed. Compounds 1 and 2 showed weak inhibition on platelet
      aggregation.

PMID- 17539655
TI  - Enantioselective total synthesis of isishippuric acid B via intramolecular
      Michael reaction.
AB  - The first enantioselective total synthesis of isishippuric acid B bearing a novel
      4,5-seco-6-norquadrane skeleton was accomplished from (R)-citronellal with use of
      a Diels-Alder cycloaddition and an intramolecular Michael addition as the ring
      forming steps. Comparison of the optical rotation of the synthetic material with
      that of the natural product confirmed the absolute configuration of isishippuric
      acid B to be 1R, 2R, 8R, and 11R.

PMID- 17539656
TI  - N-heterocyclic carbene-initiated alpha-acylvinyl anion reactivity: additions of
      alpha-hydroxypropargylsilanes to aldehydes.
AB  - Highly substituted alpha,beta-unsaturated ketones are prepared by the N
      heterocyclic carbene-initiated addition of alpha-hydroxypropargylsilanes to
      aldehydes. This strategy serves as a highly efficient alternative to the standard
      Morita-Baylis-Hillman (MBH) approaches for these types of compounds. In contrast
      to the MBH reaction, different substitution in the beta-position of the product
      (R1) can be accommodated in moderate to excellent yields with a high degree of
      control over the resulting alkene.

PMID- 17539657
TI  - Light-induced changes in an aqueous beta-carotene system stored under halogen and
      fluorescent lamps, affected by two oxygen partial pressures.
AB  - The aim of this work was to investigate the reaction kinetics of beta-carotene in
      an aqueous medium as a function of exposure to commercial lights (halogen and
      fluorescent sources) and oxygen partial pressures. The evolution of the pigment
      concentration, the changes in color, and the accumulation of a volatile compound
      (beta-ionone) were monitored during storage. The kinetics of degradation were
      mathematically modeled to compare the effects of lighting conditions and oxygen
      partial pressures. Lighting was also a critical variable in the presence of a low
      oxygen partial pressure (5 kPa), and in these conditions, the beta-carotene
      degraded completely during storage, even if more slowly than at 20 kPa of O2. The
      pigment degradation was correlated to illuminance and UVA irradiance values, but
      the different decay rates of the fluorescent lamps were explained by the
      differences in the blue region of the energy emission spectra. A halogen lamp
      gave minor negative effects on beta-carotene degradation.

PMID- 17539658
TI  - Tea polyphenol (-)-epigallocatechin 3-gallate suppresses heregulin-beta1-induced
      fatty acid synthase expression in human breast cancer cells by inhibiting
      phosphatidylinositol 3-kinase/Akt and mitogen-activated protein kinase cascade
      signaling.
AB  - Tumor-associated fatty acid synthase (FAS) is implicated in tumorigenesis and
      connected to HER2 (human epidermal growth factor receptor 2) by systemic
      analyses. Suppression of FAS in cancer cells may lead to growth inhibition and
      cell apoptosis. Our previous study demonstrated that (-)-epigallocatechin 3
      gallate (EGCG), the green tea catechin, could down-regulate FAS expression by
      suppressing EGFR (epidermal growth factor receptor) signaling and downstream
      phosphatidylinositol 3-kinase (PI3K)/Akt activation in the MCF-7 breast cancer
      cell line. Herein, we examined the effects of EGCG on FAS expression modulated by
      another member of the erbB family, that is, HER2 or HER3. We identified that
      heregulin-beta1 (HRG-beta1), a HER3 ligand, stimulated dose-dependent FAS
      expression in breast cancer cell lines MCF-7 and AU565, but not MDA-MB-453. The
      time-dependent increase in FAS expression after HRG-beta1 stimulation was also
      observed in MCF-7 cells, and this up-regulation was de novo RNA synthesis
      dependent. Treatment of MCF-7 cells with EGCG markedly inhibited HRG-beta1
      dependent induction of mRNA and protein of FAS. EGCG also decreased the
      phosphorylation of Akt and extracellular signal-regulated kinase 1/2 that were
      demonstrated as selected downstream HRG-beta1-responsive kinases required for FAS
      expression using dominant-negative Akt, PI3K inhibitors (LY294002 and
      wortmannin), or MEK inhibitor (PD98059). FAS induction by HRG-beta1 was also
      blocked by AG825, a selective HER2 inhibitor, and by genistein, a selective
      tyrosine kinase inhibitor, indicating the formation of a heterodimer between HER2
      and HER3, and their tyrosine kinase activities are essential for HRG-beta1
      mediated elevation of FAS. Additionally, growth inhibition of HRG-beta1-treated
      cells was parallel to suppression of FAS by EGCG. Taken together, these findings
      extend our previous study to indicate that EGCG may be useful in the
      chemoprevention of breast carcinoma in which FAS overexpression results from HER2
      or/and HER3 signaling.

PMID- 17539659
TI  - Prediction of molar extinction coefficients of proteins and peptides using UV
      absorption of the constituent amino acids at 214 nm to enable quantitative
      reverse phase high-performance liquid chromatography-mass spectrometry analysis.
AB  - The molar extinction coefficients of 20 amino acids and the peptide bond were
      measured at 214 nm in the presence of acetonitrile and formic acid to enable
      quantitative comparison of peptides eluting from reversed-phase high-performance
      liquid chromatography, once identified with mass spectrometry (RP-HPLC-MS). The
      peptide bond has a molar extinction coefficient of 923 M(-1) cm(-1). Tryptophan
      has a molar extinction coefficient that is approximately 30 times higher than
      that of the peptide bond, whereas the molar extinction coefficients of
      phenylalanine, tyrosine, and histidine are approximately six times higher than
      that of the peptide bond. Proline, as an individual amino acid, has a negligible
      molar extinction coefficient. However, when present in the peptide chain (except
      at the N terminus), it absorbs approximately three times more than a peptide
      bond. Methionine has a similar molar extinction coefficient as the peptide bond,
      while all other amino acids have much lower molar extinction coefficients. The
      predictability of the molar extinction coefficients of proteins and peptides,
      calculated by the amino acid composition and the number of peptide bonds present,
      was validated using several proteins and peptides. Most of the measured and
      calculated molar extinction coefficients were in good agreement, which shows that
      it is possible to compare peptides analyzed by RP-HPLC-MS in a quantitative way.
      This method enables a quantitative analysis of all peptides present in
      hydrolysates once identified with RP-HPLC-MS.

PMID- 17539660
TI  - Antioxidant activity of flavonoids isolated from young green barley leaves toward
      biological lipid samples.
AB  - Natural plant flavonoids, saponarin/lutonarin=4.5/1, isolated from young green
      barley leaves were examined for their antioxidant activity using cod liver oil,
      omega-3 fatty acids, phospholipids, and blood plasma. The saponarin/lutonarin
      (S/L) mixture inhibited malonaldehyde (MA) formation from cod liver oil by
      76.47+/-0.11% at a level of 1 micromol and 85.88+/-0.12% at a level of 8
      micromol. The S/L mixture inhibited MA formation from the omega-3 fatty acids
      eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) by 45.60+/-1.08 and
      69.24+/-0.24%, respectively, at a level of 8 micromol. The S/L mixture inhibited
      MA formation from the phospholipids lecithin I and II by 43.08+/-0.72 and 69.16+/
      2.92%, respectively, at a level of 8 micromol. It also inhibited MA formation
      from blood plasma by 62.20+/-0.11% at a level of 8 micromol. The antioxidant
      activities obtained from the S/L mixture were comparable to those obtained from
      alpha-tocopherol and butylated hydroxy toluene (BHT) in all lipids tested.

PMID- 17539661
TI  - A computational model for the prediction of aqueous solubility that includes
      crystal packing, intrinsic solubility, and ionization effects.
AB  - The optimization of aqueous solubility is an important step along the route to
      bringing a new therapeutic to market. We describe the development of an empirical
      computational model to rank the pH-dependent aqueous solubility of drug
      candidates. The model consists of three core components to describe aqueous
      solubility. The first is a multivariate QSAR model for the prediction of the
      intrinsic solubility of the neutral solute. The second facet of the approach is
      the consideration of ionization using a predicted pKa and the Henderson
      Hasselbalch equation. The third aspect of the model is a novel method for
      assessing the effects of crystal packing on solubility through a series of short
      molecular dynamics simulations of an actual or hypothetical small molecule
      crystal structure at escalating temperatures. The model also includes a Monte
      Carlo error function that considers the variability of each of the underlying
      components of the model to estimate the 90% confidence interval of estimation.

PMID- 17539662
TI  - Spontaneous formation of asymmetric lipid bilayers by adsorption of vesicles.
AB  - We have investigated the adsorption of phospholipid mixtures using neutron
      reflection. Small sonicated unilamellar vesicles (SUV) composed of DOPC and d(62)
      DPPC were incubated at 50 degrees C in contact with a silica surface using a
      method commonly employed to form supported model membranes. The composition of
      the mixed supported bilayer was found to be substantially different from that of
      the bulk vesicles in a direction indicating a higher affinity of DPPC for the
      silica surface. Formation of an asymmetric bilayer arrangement was also
      discovered in all the cases studied. DPPC tended to dominate the composition of
      the leaflet next to silica, while the outer leaflet was generally closer to the
      bulk composition. The supported bilayers also exhibited increasing interfacial
      roughness in the outer membrane leaflet in the region of the DOPC-DPPC gel-liquid
      immiscibility region. To our knowledge, this is the first time that both the
      structure and the absolute composition of a mixed-lipid supported bilayer have
      been resolved, and the results raise a number of questions regarding the
      adsorption of vesicles and the properties of supported bilayers, which are
      discussed in terms of the bulk phase diagram of DOPC and DPPC.

PMID- 17539663
TI  - Alkyl-thiol Langmuir films on the surface of liquid mercury.
AB  - The coverage dependent phase behavior of monolayers of alkyl thiols (CH3(CH2)(n
      1)SH, denoted as CnSH) on mercury was studied for chain lengths 9 <or= n <or= 22,
      using surface tensiometry and surface-specific X-ray scattering methods. At low
      coverage, a disordered single layer of surface-parallel molecules is found for
      all n. At high coverage, a monolayer of standing-up molecules is formed,
      exhibiting well-ordered phases, the structure of which is n- and coverage
      dependent. The molecular chains pack in a centered rectangular unit cell, with an
      approximately 27 degrees tilt from the surface normal toward nearest neighbors.
      The strong sulfur-mercury bond induces a noncentered unit cell for the
      headgroups, incorporating one mercury atom per two thiol molecules. The small but
      significant differences in structure of these films on gold and on mercury are
      discussed and assigned to the different structure of the subphase: long-range
      ordered crystal for gold and short-range-ordered liquid for mercury.

PMID- 17539664
TI  - Anisotropic wettability on imprinted hierarchical structures.
AB  - A series of two-level hierarchical structures on polystyrene (PS) and poly(methyl
      methacrylate) (PMMA) were fabricated using sequential nanoimprinting lithography
      (NIL). The hierarchical structures consist of micrometer and sub-micrometer scale
      grating imprinted with varying orientations. Through water contact angle
      measurements, these surface hierarchical structures showed a wide range of
      anisotropic wettabilities on PMMA and PS, with PMMA having an anisotropic
      wettability from 6 degrees to 54 degrees and PS having an anisotropic wettability
      from 8 degrees to 32 degrees. At the same time, the water contact angle of PMMA
      and PS can be tuned to nearly 120 degrees without modifying the surface
      chemistry. A tunable anisotropic wettability is beneficial for applications where
      controlling the direction of liquid flow is important, such as in microfluidic
      devices.

PMID- 17539665
TI  - Dielectric behavior of lipid vesicles: the case of L-alpha
      dipalmitoylphosphatidylcholine vesicles as a function of size and temperature.
AB  - We present an extensive set of radio wave dielectric relaxation spectroscopy
      measurements of aqueous suspensions of different size unilamellar L-alpha
      dipalmitoylphosphatidylcholine (DPPC) vesicles, in a temperature range between 15
      and 55 C, where the lipidic bilayer experiences structural transitions from the
      gel to the rippled phase (at the pretransition temperature) and from the rippled
      to the liquid phase (at the main transition temperature). The dielectric spectra
      have been analyzed in the light of the Cole-Cole relaxation function, and the
      main dielectric parameters-the dielectric increment Deltaepsilon and the mean
      relaxation frequency omega(0)--have been evaluated as a function of temperature.
      These parameters display a very complex phenomenology, depending on the
      structural arrangement of the lipid-water interface. The structural parameters
      that govern the dielectric behavior of these systems associated with the lipid
      bilayer have been recognized within a recent dynamic mean-field model we have
      proposed, aimed to predict the dipolar relaxation of an array of strongly
      interacting dipoles anchored to a flat or corrugated surface. They are the
      prefactor A(T) of the distance-dependent part of the effective dipolar
      interaction energy, the term Gamma(vis), that takes into account the damping of
      the dipolar motion, the average dipolar distance related to the area a(0) per
      polar head, and the bilayer thickness. The present analysis furnishes, from a
      phenomenological point of view, the dependence of these parameters on the
      temperature and on the vesicle size.

PMID- 17539666
TI  - Novel polymerizable surfactants from 1:1 mixtures of alkylcarboxylic acids and
      norbornene methylenamine.
AB  - A new family of polymerizable surfactants was synthesized starting from a 1:1
      mixture of alkylcarboxylic acids (C(10) to C(16)) and norbornene methyleneamine.
      The ion-paired surfactants exhibited cloud temperatures, surface activity, and
      critical aggregation concentrations that differed according to the chain length,
      with a variation indicating a strongly associated ion pair. Light-scattering
      measurements and electron microscopy observations confirmed the spontaneous
      formation of stable vesicles (90 nm < d < 370 nm). Also, NMR experiments showed
      the enclosing of the norbornene part inside the vesicle membrane. Moreover, the
      addition of sodium chloride allowed the formation of a tubular structure leading
      to a viscous or gel-like solution. Finally, a preliminary vinylic polymerization
      test proved the polymerizable character of these ion-paired surfactants by an
      organometallic catalysis, leading to partially polymerized vesicles.

PMID- 17539667
TI  - Preorientation of olefins toward a single photodimer: cucurbituril-mediated
      photodimerization of protonated azastilbenes in water.
AB  - With the view to establishing the generality of cucurbit[8]uril as a template,
      the photodimerization of hydrochloride salts of eight azastilbenes has been
      investigated in an aqueous medium. Whereas in solution upon excitation all of
      these olefins yield products of geometric isomerization, cyclization, and
      hydration, in the presence of cucurbit[8]uril the predominant product is that of
      dimerization. Such a change in product distribution is attributed to the
      localization of the olefins by the host cucurbit[8]uril. Most importantly,
      instead of a mixture of dimers, predominantly a single dimer was obtained in each
      case. The nature of the dimer that was formed could be rationalized on the basis
      of the principles of "best fit" and "minimization of electrostatic repulsion".
      The superior ability of cucurbit[8]uril compared to micelles to act as a
      templating agent is attributed to its ability to provide a reaction cavity that
      is tight and time-independent.

PMID- 17539668
TI  - Probing chitosan and phospholipid interactions using Langmuir and Langmuir
      Blodgett films as cell membrane models.
AB  - The interaction between chitosan and Langmuir and Langmuir-Blodgett (LB) films of
      dimyristoyl phosphatidic acid (DMPA) is investigated, with the films serving as
      simplified cell membrane models. At the air-water interface, chitosan modulates
      the structural properties of DMPA monolayers, causing expansion and decreasing
      the monolayer elasticity. As the surface pressure increased, some chitosan
      molecules remained at the interface, but others were expelled. Chitosan could be
      transferred onto solid supports alongside DMPA using the LB technique, as
      confirmed by infrared spectroscopy and quartz crystal microbalance measurements.
      The analysis of sum-frequency vibration spectroscopy data for the LB films
      combined with surface potential measurements for the monolayers pointed to
      chitosan inducing the ordering of the DMPA alkyl chains. Furthermore, the
      morphology of DMPA LB films, studied with atomic force microscopy, was affected
      significantly by the incorporation of chitosan, with the mixed chitosan-DMPA
      films displaying considerably higher thickness and roughness, in addition to
      chitosan aggregates. Because chitosan affected DMPA films even at pressures
      characteristic of cell membranes, we believe this study may help elucidate the
      role of chitosan in biological systems.

PMID- 17539669
TI  - Modeling of the adsorption and desorption of CO2 on Cu/ZrO2 and ZrO2 catalysts.
AB  - The interaction between carbon dioxide and two zirconia catalysts-a Cu/ZrO2
      catalyst containing 34% copper and a pure ZrO2 catalyst-was studied by pulse
      adsorption and temperature-programmed desorption methods. Kinetic modeling by
      nonlinear regression was applied to acquire information on the adsorption and
      desorption of CO2 relevant in the synthesis of methanol from carbon dioxide. A
      model that included three types of adsorption sites described well the
      experimental data for both Cu/ZrO2 and ZrO2. The model assumed first-order
      kinetics and a Freundlich-type logarithmic dependence of adsorption enthalpy on
      surface coverage. The parameters of the model were well identified and were in
      the physically meaningful range. The results indicate that, at 30 degrees C, on
      both catalysts, carbon dioxide adsorbs reversibly on one type of site and
      irreversibly on two other types of sites.

PMID- 17539670
TI  - A metabonomic investigation on the biochemical perturbation in liver failure
      patients caused by hepatitis B virus.
AB  - A metabonomic study was performed to investigate the biochemical perturbation of
      the serum samples from liver failure patients induced by hepatitis B virus (HBV;
      n=24) and control normal subjects (n=23). The serum metabonome was detected using
      gas chromatography-mass spectrometry (GC-MS) technique integrated with a
      commercial mass spectral library for the peak identification. After peak
      deconvolution, identification, and matching, the acquired GC-MS data were
      normalized and processed by principal component analysis (PCA) and canonical
      discriminant analysis (CDA). Specific changes in the metabolic composition of
      serum samples from patients including amino acids (AAs) and glucose were shown in
      GC-MS total ion current (TIC) chromatograms. The distinctive biochemical
      difference between the healthy subjects and liver failure patients was displayed
      by the pattern recognition methods. We also found that the liver failure patients
      with different degree of severity categorized as MELD (model for end-stage of
      liver diseases) could be clearly classified by the corresponding metabonomic
      data. In comparison, the current routine clinical indices cannot characterize the
      global phenotyping of liver failure. The result demonstrated that the GC-MS
      technique is an alternative tool for the characterization of the metabolic
      perturbation and the metabonomic study promises to provide an integrative
      criterion to evaluate the severity and the prognosis of liver diseases.

PMID- 17539671
TI  - Biomarker discovery from uveal melanoma secretomes: identification of gp100 and
      cathepsin D in patient serum.
AB  - There is a necessity to better characterize uveal melanoma (UM) tumors according
      to their metastasis potential at an early stage. In this study we report the
      identification of potential biomarkers by a combination of proteomics-related
      approaches: the characterization of UM cell secretomes, the analysis of UM
      autoantibodies, and the differential depleted serum proteome analysis. We
      describe a possible role of cathepsin D, syntenin, and gp100 in UM as potential
      biomarkers.

PMID- 17539672
TI  - A beta-galactosidase-based bacterial two-hybrid system to assess protein-protein
      interactions in the correct cellular environment.
AB  - The vast majority of proteins functions in complex with one or more of the same
      or other proteins, indicating that protein-protein interactions play crucial
      roles in biology. Here, we present a beta-galactosidase reconstitution-based
      bacterial two-hybrid system in which two proteins of interest are fused to two
      non-functional but complementing beta-galactosidase truncations (Delta alpha and
      Delta omega). The level of complemented beta-galactosidase activity, driven by
      the protein-protein recognition between both non-beta-galactosidase parts of the
      chimeras, reflects whether or not the proteins of interest interact. Our approach
      was validated by reconfirming some well-established Escherichia coli cytoplasmic
      and membranous interactions, including well-chosen mutants, and providing the
      first in vivo evidence for the transient periplasmic interaction between
      Rhodobacter capsulatus cytochrome c2 and cytochrome c peroxidase. We demonstrated
      the major advantages of this in vivo two-hybrid technique: i) analyses of
      interactions are not limited to particular cellular compartments, ii) the
      potential of using the system in mutation-driven structure-function studies, and
      iii) the possibility of its application to transiently interacting proteins.
      These benefits demonstrate the relevance of the method as a powerful new tool in
      the broad spectrum of interaction assessment methods.

PMID- 17539673
TI  - Proteomic analysis of human cervical-vaginal fluids.
AB  - The pathophysiology of vaginal conditions is still ill-defined at a molecular
      level. Because the proteome of the human cervical-vaginal fluid (CVF) has not
      been reported to date, we undertook the identification of proteins present in the
      cell-free fraction of these fluids. Proteins were separated bidimensionally (2-D)
      by isoelectrofocusing (pH 3-11) followed by SDS-polyacrylamide electrophoresis.
      The proteins of 147 spots were identified by matrix-assisted laser desorption/
      ionization-time-of-flight-mass spectrometry (MALDI-TOF/TOF). This approach was
      supplemented by immunoassays for markers of neutrophils (myeloperoxidase, MPO;
      neutrophil gelatinase-associated lipocalin, NGAL/HNL) and eosinophils (eosinophil
      cationic protein: ECP) and by immunoblotting (lactoferrin, calgranulins A and B
      and annexins A1 and A3. Nearly half of the proteins (69/147) and protein
      fragments detected were found to be plasma components, on the basis of which the
      human CVF can be broadly considered a plasma transudate. Although the pattern of
      protein spots was very similar for all fluids analyzed, a relative overabundance
      of major plasma proteins such as albumin, transferrin, immunoglobulins,
      apolipoproteins, alpha-1-acid glycoprotein 1, and calgranulins was associated
      with the presence of a high number of polymorphonuclear leukocytes in the lavages
      from which those cell-free fluids had been obtained. Instead, fluids from women
      experiencing vulvovaginal candidiasis did not show differences in the protein
      maps compared with asymptomatic individuals. Neutrophil and eosinophil granule
      secretion proteins were also detected in variable amounts in the lavage fluids by
      both immunoassay and immunoblotting, indicating polymorphonuclear cell
      activation.

PMID- 17539674
TI  - The influence of the molecular dipole on the electronic structure of isomeric
      icosahedral dicarbadodecaborane and phosphacarbadodecaborane molecular films.
AB  - We compare the molecular films of three different isomers of closo
      dicarbadodecaborane (orthocarborane (1,2-C2B10H12), metacarborane (1,7-C2B10H12),
      paracarborane (1,12-C2B10H12)) and two related icosahedral cage molecules, 1
      phospha-2-carbadodecaborane (1,2-PCB10H11) and 1-phospha-7-carbadodecaborane (1,7
      PCB10H11) adsorbed on a variety of substrates. While the experimental electronic
      structure from combined photoemission and inverse photoemission studies of the
      molecular films are in good agreement with semiempirical calculations for the
      isolated molecule, there is a shift in the chemical potential for each molecule.
      The experimental position of the molecular chemical potential implicates an
      influence of both interface and adsorbate dipole.

PMID- 17539675
TI  - Photophysical properties of ruthenium bipyridine (4-carboxylic acid-4'-methyl
      2,2'-bipyridine) complexes and their acid-base chemistry.
AB  - Photophysical properties such as absorption and emission spectra, lifetimes, and
      redox potentials of eight ruthenium complexes, Ru(LL)2(MebpyCOOH)2+, where LL
      represents bpy, phen, Me2bpy, Me4bpy, (MeO)2bpy, (EtO)2bpy, Cl2bpy, and NO2phen,
      have been measured. The acid dissociation constants of ground and excited states
      have been determined. The ground-state pKa values were obtained from the pH
      dependence of the complex absorbance changes. The excited-state pKa* values were
      extracted from the emission titration curve and corrected for the excited-state
      lifetime of both protonated and deprotonated species. The largest DeltapKa, pKa*
      pKa, found for Ru(Me2bpy)2(MebpyCOOH)2+ and Ru(Me4bpy)2(MebpyCOOH)2+ of 1.7
      indicate that MebpyCOOH gains most of the MLCT excited-state electron. The big
      negative DeltapKa found for Ru(Cl2bpy)2(MebpyCOOH)2+, -4.2, clearly indicates the
      metal-to-ligand charge transfer to the Cl2bpy ligands.

PMID- 17539676
TI  - Conformational analysis of the electron-transfer kinetics across oligoproline
      peptides using N,N-dimethyl-1,4-benzenediamine donors and pyrene-1-sulfonyl
      acceptors.
AB  - Photoinduced intramolecular charge separation across proline-bridged donor
      acceptor complexes of the type Pyr-(Pro)n-DMPD (where Pyr=pyrene-1-sulfonyl and
      DMPD=N,N-dimethyl-1,4-phenylenediamine) was studied. The steady-state emission
      spectrum for n=0, 1, 2, 3 showed an increase in emission intensity with the
      number of proline residues. Time-dependent emission measured by streak camera
      showed increasing emission signal amplitude with increasing n, along with a
      decrease in decay rate. In all these studies, Pyr-Pro was used as a control
      complex for the decay of the excited pyrene acceptor moiety without the donor
      DMPD. Detailed photon counting experiments carried out in DMF/water, DMF, and
      toluene showed single-exponential kinetics for n=0, 1 and multiexponential
      kinetics for n=2, 3. Rate constants observed in DMF are for n=0, k=approximately
      5x10(10) s(-1); n=1, k=9.70x10(8) s(-1); n=2, k=35.9x10(8) s(-1) (70%) and
      5.58x10(8) s(-1) (30%); and n=3, k=16.6x10(8) s(-1) (55%) and 3.87x10(8) s(-1)
      (45%). These results show that a significant percentage of the n=2 and n=3
      molecules undergo faster electron transfer than for the n=1 case. Conformational
      analysis for Pyr-(Pro)n-DMPD molecules in water showed that whereas only one
      conformation is possible for n=1, eight are possible for n=2, and 32 are possible
      for n=3. Calculation of the free energy and electronic coupling for these
      conformers in water showed that only a few of these conformations have the
      appropriate energy and electronic coupling to be observed in the experimental
      time window from 20 ps to 20 ns. Assignment of the conformers undergoing electron
      transfer in Pyr-(Pro)n-DMPD for n=2 and 3 was based on the values for the n=1
      case, for which the measured rate constant is approximately 10(9) s(-1) and the
      calculated electronic coupling matrix element Hda is 297 cm(-1). The similarity
      in ground state energy between the cis and trans conformers for n=2 and 3, their
      use in aqueous-organic and organic solvents, and the nature of the Pyr and DMPD
      acceptor and donor groups could be contributing causes for the multiexponential
      kinetics, which was not observed for the metal ion derivatives of proline
      peptides studied earlier in aqueous solution.

PMID- 17539677
TI  - Structural and thermodynamic aspects of ionic solvation in concentrated aqueous
      poly(ethylene glycol).
AB  - Solvation of ions in concentrated aqueous poly(ethylene glycol) (PEG) has been
      studied from thermodynamic and structural viewpoints using ion-transfer
      voltammetry at the interface between aqueous and nitrobenzene phases and X-ray
      absorption fine structure (XAFS). Systematic changes in the ion-transfer
      potential from water to aqueous PEG have been confirmed for several ions relative
      to the corresponding potential of tetraethylammonium ion (Et4N+), which is almost
      independent of PEG concentration. The results obtained for alkali cations
      strongly suggest the involvement of their complexation with PEG even in
      relatively diluted PEG solutions. It has been implied that the solvation
      circumstances of Br- and ClO4- are drastically altered when the PEG concentration
      becomes higher than particular critical values (e.g., 30-50% PEG200), where free
      water molecules are diminished because of the hydration of PEG. XAFS measurements
      have also been performed for K+ and Br- to get direct evidence for these
      findings. Although the spectra at the K K-edge clearly indicate the presence of a
      PEG complex of K+ in relatively diluted PEG solutions ( approximately 33%
      PEG200), an obvious increase in its ion-transfer potential has been detected at
      lower PEG concentrations, indicating that complexes formed at the interface
      rather than in bulk solution are transferred into an organic phase. Br- is fully
      hydrated in 0-50% PEG solutions, whereas some water molecules are replaced by PEG
      when the PEG concentration increases. Increasing the PEG concentration causes
      decreases in the coordination number from 6 in water to 2-3 in neat PEG. Thus,
      the present approach not only has elucidated the structural and thermodynamic
      aspects of ionic solvation in aqueous PEG but also has provided the information
      of the hydration of PEG.

PMID- 17539678
TI  - Quasi-isochoric superheating of nanoparticles embedded in rigid matrixes.
AB  - A thermodynamic model for pressure-induced quasi-isochoric superheating of
      nanoparticles embedded in rigid matrixes was established quantitatively by
      introducing the size dependence of melting enthalpy. The accuracy of the
      developed model was verified with the reported experimental data of Sn and Pb
      nanoparticles encapsulated in fullerene-like graphitic shells (FGS) as well as Ge
      nanoparticles embedded in SiO2. The mechanism behind the smaller superheating for
      Al nanoparticles embedded in Al2O3 was also studied. It was found that the extent
      of the superheating is determined by the pressure, which is in turn related to
      the confinement effect and to the size of the nanoparticles. Through the
      knowledge obtained in this study, it can be concluded that the extreme
      superheating of nanoparticles can be achieved on the proviso that they are
      encased in a sufficiently rigid matrix, while the size of nanoparticles is small
      enough.

PMID- 17539679
TI  - Thermodynamics of ethyl p-tert-butylcalix[5]arene pentanoate and its cation
      complexes in nonaqueous media.
AB  - The solution behavior of ethyl p-tert-butylcalix[5]arene pentanoate, EtCalix(5),
      in various protic and aprotic solvents has been assessed from the standard Gibbs
      energies of transfer of this ligand from acetonitrile to other solvents. These
      data were derived from solubility measurements of EtCalix(5) in different media.
      It is concluded that in solvents in which metal cation salts are predominant as
      ionic species in solution (within a low concentration range), the solvation of
      the ligand will not contribute significantly to the thermodynamics of cation
      complexation as a result of the medium effect. Various analytical techniques were
      used to identify the sites of ligand-cation interaction (1H NMR) and the
      composition (conductance and calorimetric measurements) of the metal-ion
      complexes in the various solvents. Titration calorimetry (direct and competitive)
      was used to thermodynamically characterize the cation binding ability of
      EtCalix(5) and gain quantitative information on the complex stability and the
      factors controlling it. Given the large bulk of data reported in the literature
      wrongly placed under the thermodynamic umbrella, particular emphasis is made
      about the need of identifying the process taking place in solution prior to
      proceeding with its thermodynamic characterization. The results are compared with
      those for the ethyl ester derivative of the cyclic tetramer, EtCalix(4). It is
      concluded that in moving from EtCalix(4) to EtCalix(5), (i) the selectivity of
      the latter for cations is swallowed toward the larger cations and (ii) although
      the number of binding sites increases, these are not able to exert the efficient
      control upon the ligand-cation binding ability as that found for the tetramer
      ester and these cations in these solvents.

PMID- 17539680
TI  - Photoinduced electron transfer in arylacridinium conjugates in a solid glass
      matrix.
AB  - The photophysical properties of a series of 9-arylacridinium conjugates in solid
      glass matrices composed of sucrose octaacetate have been determined. The
      fluorescence of the charge-shift states is significantly enhanced because of the
      retardation of nonradiative pathways for back-electron transfer. Changes of more
      than 3 orders of magnitude in back-electron-transfer rates (sucrose octaacetate
      glass vs conventional solvents at room temperature) were observed. Transient
      spectra displayed long-lived charge-shift species in the microsecond time regime
      for thianthrene acridinium conjugates. The rate retardation is associated with
      slow solvation times for surrounding solvent layers in the solid matrix. The red
      edge effect (excitation wavelength-dependent fluorescence) for the arylacridinium
      ions in solid glass confirms the microheterogeneity of the sucrose octaacetate
      medium.

PMID- 17539682
TI  - Unexpected reactivity of the burgess reagent with thiols: synthesis of
      symmetrical disulfides.
AB  - Reaction of the Burgess reagent with a series of aliphatic and aromatic thiols
      led to the corresponding symmetrical disulfides in high yields. No olefins were
      detected in the reactions of aliphatic thiols.

PMID- 17539683
TI  - Mechanistic studies on the stereoselective formation of beta-mannosides from
      mannosyl iodides using alpha-deuterium kinetic isotope effects.
AB  - Stereoselective synthesis of beta-mannosides is one of the most challenging
      linkages to achieve in carbohydrate chemistry. Both the anomeric effect and the
      C2 axial substituent favor the formation of the axial glycoside (alpha-product).
      Herein, we describe mechanistic studies on the beta-selective glycosidation of
      trimethylene oxide (TMO) using mannosyl iodides. Density functional calculations
      (at the B3LYP/6-31+G(d,p):LANL2DZ level) suggest that formation of both alpha-
      and beta-mannosides involve loose S(N)2-like transition-state structures with
      significant oxacarbenium character, although the transition structure for
      formation of the alpha-mannoside is significantly looser. alpha-Deuterium kinetic
      isotope effects (alpha-DKIEs) based upon these computed transition state
      geometries match reasonably well with the experimentally measured values: 1.16 +/
      0.02 for the beta-linkage (computed to be 1.15) and 1.19 +/- 0.05, see table 2
      for the alpha-analogue (computed to be 1.26). Since it was unclear if beta
      selectivity resulted from a conformational constraint induced by the anomeric
      iodide, a 4,6-O-benzylidine acetal was used to lock the iodide into a chairlike
      conformation. Both experiments and calculations on this analogue suggest that it
      does not mirror the behavior of mannosyl iodides lacking bridging acetal
      protecting groups.

PMID- 17539684
TI  - Diverse functionalization of thiazolo ring-fused 2-pyridones.
AB  - Thiazolo ring-fused 2-pyridones have proven to be highly interesting scaffolds
      for the development of biologically active compounds. Many methods are today
      available to introduce a variety of substituents in the 2-pyridone part of the
      heterocycle. Herein we disclose how a diverse set of substituents can be
      introduced in the thiazolo ring, with possibilities to vary also the spatial
      arrangement of the substituents. A key intermediate is the oxidized framework 9
      for which an effective synthesis is described. The thiazolo part of this system
      can be substituted either via conjugate additions, resulting in trans
      selectivity, or via microwave-assisted Heck couplings that result in unsaturated
      aryl-substituted analogues. The scaffold can also be lithiated followed by the
      addition of various electrophiles, which increases the diversification potential
      substantially, as exemplified with the introduction of halogens, alkyl, acyl, and
      amide substituents.

PMID- 17539685
TI  - N-methyl-N-nosyl-beta(3)-amino acids.
AB  - N-Methyl-beta(3)-amino acids are important building blocks in the synthesis of
      biologically active molecules. A very simple and efficient approach to transform
      natural alpha-amino acids into their corresponding N-methyl-beta(3)-amino acids
      is here presented. In the method, the key intermediates N-methyl-N-nosyl-alpha
      aminoacyldiazomethanes are prepared in only one step, by a simple treatment of
      the corresponding N-nosyl-alpha-aminoacyl chlorides with diazomethane. The
      synthetic route takes advantage from the use of the nosyl group. This N-masking
      moiety activates the NH function, and the N-methylation can directly occur during
      the acylation step of diazomethane, rendering useless a second step that instead
      is shown to be necessary in all the classical procedures already reported for the
      preparation of N-methyl-beta(3)-amino acids. The Wolff rearrangement of N-methyl
      N-nosyl-alpha-aminoacyldiazomethanes provides the corresponding N-methyl-N-nosyl
      beta(3)-amino acids with total retention of the chiral configuration of the
      starting alpha-amino acids. No epimerization of the chiral carbon atom is
      observed also when N-methyl-N-nosyl-beta(3)-amino acids are transformed into
      chlorides and coupled with alpha-amino acid methyl esters to achieve model
      scaffolds for biologically important modified peptides.

PMID- 17539686
TI  - Synthesis of photostable amine-reactive fluorescent dyes by postsynthetic
      conversion of bromide dithienothiophene derivatives.
AB  - The synthesis, purification, and spectral properties of new dithienothiophene
      based fluorescent dyes with a terminal alkyl bromide group are described. The
      bromides were easily converted to isothiocyanates and N-succinimidyl esters by
      appropriate chemical transformations with sodium thiocyanate or N
      hydroxysuccinimide. The new fluorophores exhibited intense fluorescence emission
      and high photostability. Their suitability for bioanalytical applications was
      evaluated through conjugation with amine-reactive polystyrene microspheres and
      IgG anti-CD3 monoclonal antibody.

PMID- 17539687
TI  - Improved plasmalogen synthesis using organobarium intermediates.
AB  - An improved synthesis of plasmalogen type lipids is described. Transmetalation of
      lithioalkoxy allyl intermediates with BaI(2) and subsequent alkylation with 1
      iodoalkanes enables the stereoselective formation of O-(Z)-alkenyl ether as
      precursors for the synthesis of plasmenyl- and bisplasmenylcholines. This method
      provides a simple and adaptable approach for the stereocontrolled synthesis of
      plasmenyl derivatives with variations at the sn-1, sn-2, and sn-3 positions of
      the glycerol backbone.

PMID- 17539688
TI  - Dipolar cycloaddition of ethyl isocyanoacetate to 3-chloro-2-(methylthio)/2
      (methylsulfonyl)quinoxalines: highly regio- and chemoselective synthesis of
      substituted imidazo[1,5-a]quinoxaline-3-carboxylates.
AB  - An efficient route for regio- and chemoselective synthesis of substituted 3
      (carboethoxy)imidazo[1,5-a]quinoxalines and novel diimidazo[1,5-a:5',1'
      c]quinoxalines via base-induced cycloaddition of ethyl isocyanoacetate to
      unsymmetrically substituted 3-chloro-2-(methylthio)/2
      (methylsulfonyl)quinoxalines has been reported.

PMID- 17539689
TI  - Application of a 6pi-1-azatriene electrocyclization strategy to the total
      synthesis of the marine sponge metabolite ageladine A and biological evaluation
      of synthetic analogues.
AB  - A 12-step synthesis of the angiogenesis inhibitory marine metabolite ageladine A
      is reported. The key steps include a 6pi-1-azatriene electrocyclization for
      formation of the pyridine ring and a Suzuki-Miyaura coupling of N-Boc-pyrrole-2
      boronic acid with a chloroimidazopyridine. In addition, an assessment of the
      biological activity of a variety of synthetic analogues of ageladine A prepared
      during this synthesis is described.

PMID- 17539690
TI  - Facile S(N)2' coupling reactions of wittig reagents with dimethyl
      bromomethylfumarate: synthesis of enes, dienes, and related natural products.
AB  - A new simple and efficient synthetic protocol with an ample scope has been
      demonstrated, by employing S(N)2' coupling reactions of a variety of Wittig
      reagents with dimethyl bromomethylfumarate to obtain the corresponding enes,
      dienes, and related natural and unnatural products.

PMID- 17539691
TI  - Controlled deposition of gold nanowires on semiconducting and nonconducting
      surfaces.
AB  - One of the pressing problems in advancing nanoelectronic applications and systems
      is to develop a simple means of freely connecting at a nanometric level
      electronic components under ambient conditions without the need for vacuum or
      electron or ion beam operational steps. Such environments may have detrimental
      effects on the molecular or biomolecular constituents of molecular electronic
      circuits. Although there has been defined progress in connecting structures that
      are of nanometric dimension, new methods in this area of nanotechnology with
      general applicability add to the arsenal of tools for addressing this standing
      problem. This paper addresses freely placing under ambient conditions, with
      fountain pen nanolithography, a 120 nm dimension line of gold nanocolloids
      deposited with precise registration in a 100 nm gap between two 250 nm wide
      conducting electrodes patterned by electron beam lithography.

PMID- 17539693
TI  - Increasing global burden of cardiovascular disease in general populations and
      patients with schizophrenia.
AB  - Cardiovascular disease (CVD), which includes coronary heart, cerebrovascular, and
      peripheral vascular disease, is the leading cause of death in the United States
      and most developed countries, accounting for about 50% of all deaths. The major
      risk factors include obesity and its consequences, dyslipidemia, hypertension,
      insulin resistance leading to diabetes, and cigarette smoking. In developing
      countries, CVD will become the leading cause of death due to alarming increases
      in obesity, sedentary lifestyles, cigarette smoking, and improvements in
      prevention and treatment of malnutrition and infection. Compared with
      nonschizophrenics, patients with schizophrenia have a 20% shorter life expectancy
      (i.e., from 76 to 61 years). In general populations, about 1% die from suicide
      compared with about 10% among patients with schizophrenia (relative risk = 10).
      For CVD, the corresponding figures are 50% and about 75% (relative risk = 1.5).
      In patients with schizophrenia, however, CVD occurs more frequently and accounts
      for more premature deaths than suicide. Patients with schizophrenia have
      alarmingly higher rates of obesity, dyslipidemia, hypertension, diabetes, and
      cigarette smoking than nonschizophrenic individuals in the general population.
      Compounding these data, patients with schizophrenia have less access to medical
      care, consume less medical care, and are less compliant. Primary prevention
      strategies should include the choice of antipsychotic drug regimens that do not
      adversely affect the major risk factors for CVD.

PMID- 17539694
TI  - Antipsychotic medications: metabolic and cardiovascular risk.
AB  - Individuals with serious mental illness experience excess morbidity and
      mortality, including an increased prevalence of diabetes mellitus and
      cardiovascular disease. Cardiovascular disease is the leading cause of death in
      persons with serious mental illness, and the elevated prevalence of obesity in
      this population is of particular concern. Obesity is an independent
      cardiometabolic risk factor that impacts morbidity and mortality and contributes
      to the development of other cardiometabolic risk factors, such as dyslipidemia
      and hypertension. In addition, obesity is a major risk factor for type 2
      diabetes, with the relative risk of diabetes increasing with body mass index.
      Increased abdominal fat is strongly associated with insulin resistance, which can
      lead to impaired glucose regulation. Abdominal obesity, hyperglycemia,
      hypertension, and dyslipidemia are key components of the metabolic syndrome, a
      constellation of cardiometabolic risk factors linked by their common association
      with insulin resistance. Evidence from large clinical samples indicates a high
      prevalence of metabolic syndrome and all of its components in persons with
      serious mental illness, particularly in patients with schizophrenia. In addition,
      psychotropic agents, including some antipsychotic medications, are associated
      with substantial weight gain, as well as with adiposity-dependent and possibly
      adiposity-independent changes in insulin sensitivity and lipid metabolism, which
      increase the risk of diabetes and cardiovascular disease. Among the second
      generation antipsychotics, clozapine and olanzapine are associated with the
      highest risk of substantial weight gain, similar to the weight gain potential
      associated with low-potency first-generation antipsychotics such as thioridazine
      or chlorpromazine, as well as with an increased risk of diabetes and
      dyslipidemia. Various strategies for monitoring cardiometabolic risk factors in
      patients with mental illness are discussed in this review.

PMID- 17539695
TI  - Implementation of monitoring and management guidelines for second-generation
      antipsychotics.
AB  - It has long been known that psychiatric patients experience increased morbidity
      and mortality associated with a range of physical disorders. Lifestyle,
      inadequate health care, and a variety of other factors all contribute to the poor
      physical health of people with severe mental illness. Second-generation
      antipsychotics have gained widespread acceptance for the management of patients
      with schizophrenia and other forms of severe mental illness. While demonstrating
      several advantages over first-generation antipsychotics, second-generation
      antipsychotics have been found to cause or exacerbate several metabolic
      disorders, including diabetes, obesity, dyslipidemia, and metabolic syndrome.
      These disorders are closely linked and consistently associated with the
      development of cardiovascular disease, with varying prevalence rates depending on
      the second-generation antipsychotic used. As a result, several authoritative
      guidelines have been developed for the monitoring and management of metabolic
      disturbances in schizophrenia and other forms of severe mental illness.
      Specifically, the guidelines and recommendations generated from the Mount Sinai
      Conference on Medical Monitoring and the American Diabetes Association/American
      Psychiatric Association Consensus Development Conference on Antipsychotic Drugs
      and Obesity and Diabetes call for a more integrated and cooperative approach
      between primary care physicians and mental health care providers to improve the
      quality of health care for people with severe mental illness. By routinely
      performing physical health monitoring, referrals, and/or treatment for patients
      with schizophrenia and other forms of severe mental illness, mental health care
      providers can take a lead role in transforming the current system of fragmented
      mental and physical health services into a system focused on early intervention,
      wellness, and recovery.

PMID- 17539696
TI  - Behavioral therapy for weight loss in patients with schizophrenia.
AB  - Compared with the general population, individuals with schizophrenia demonstrate
      an increased prevalence of obesity. While most antipsychotics are associated with
      weight gain, certain second-generation antipsychotics (SGAs) appear to be
      especially problematic. Weight gain and obesity are highly distressing to these
      patients, can reduce treatment adherence, and may increase the relative risk of
      serious medical conditions and all-cause premature mortality. The selection of an
      antipsychotic on the basis of its effectiveness and relative side effect profile
      is recognized as an important initial consideration in the treatment of
      schizophrenia. However, less is known regarding the efficacy of dietary,
      pharmacologic, and behavioral therapy in reducing antipsychotic-related weight
      gain and obesity. Behavioral therapy, in particular, is understudied, and there
      are relatively few controlled trials of its effectiveness in reducing SGA-induced
      weight gain. Although weight loss resulting from behavioral therapy has been
      observed mostly as a result of effective short-term interventions, controlled
      behavioral studies do exist to suggest that weight can be controlled long term.
      In addition, a small pilot study in patients with schizophrenia or
      schizoaffective disorder recently demonstrated that behavioral therapy that
      utilizes stepped interventions, involving body weight self-monitoring, diet, and
      exercise, can prevent weight gain in patients initiating treatment with SGAs.
      Additional studies of behavioral therapy for long-term weight control in patients
      with schizophrenia and other forms of severe mental illness are warranted.

PMID- 17539697
TI  - Bridging the gap between mental and physical health: a multidisciplinary
      approach.
AB  - People with serious mental illnesses have higher rates of morbidity and premature
      mortality compared with the general population. This population loses from 13 to
      over 20 years of life compared with their nonpsychiatric cohorts. A multitude of
      factors contribute to this silent tragedy. A major problem is that multiple
      barriers exist, making it difficult for individuals with serious mental illness
      to access quality health care. Additionally, compared with the average American,
      people with serious mental illness are more likely to engage in unhealthy
      lifestyle practices, such as lack of regular physical activity, poor nutrition
      and overeating, smoking and other substance abuse, irregular and inadequate
      sleep, and failure to visit health care practitioners regularly. These unhealthy
      behaviors and the added burden of anti-psychotic medication side effects increase
      the risk for cardiac and metabolic diseases. However, best-practice models exist
      that provide the knowledge and tools to assist people with serious mental illness
      in making informed decisions about healthier lifestyle behaviors, including
      addressing tobacco use and excess weight. The challenge is how to integrate these
      practices effectively into routine behavioral health care. The growing problem of
      premature death calls for urgent public action to transform the current mental
      health care system into a more integrated system of care. Because of their
      holistic training and approach to care, nurses are well prepared to work
      collaboratively with both mental and physical health care providers and systems.
      In the new mental health care system, both psychiatric and physical health care
      providers will need to broaden their treatment paradigm to address the whole
      person. An integral part of behavioral health services will be to ensure that the
      health status of all individuals is assessed, that there are medical monitoring
      protocols in place for people taking antipsychotic medication, that each
      individual has a primary care provider, and that there is an effective mechanism
      in place for communication between behavioral health and primary care providers.
      A transformation of the existing mental health care system toward a system that
      utilizes a coordinated, multi-disciplinary, holistic approach not only may
      effectively bridge the existing gap between mental and physical health, but also
      may ultimately save lives.

PMID- 17539698
TI  - Switching antipsychotics as a treatment strategy for antipsychotic-induced weight
      gain and dyslipidemia.
AB  - Patients taking antipsychotic medications for psychiatric disorders also have
      many risk factors for medical comorbidities and early death. While these risk
      factors were present before the arrival of the newer antipsychotic medications,
      the overall risk factor burden is exacerbated for those high-risk patients whose
      antipsychotic therapy causes or aggravates obesity or dyslipidemia. Therefore,
      there is an urgent need for effective interventions to address problems related
      to the additional iatrogenic burden from weight gain and dyslipidemias caused by
      antipsychotic medications. For patients with schizophrenia, complete
      discontinuation of antipsychotic therapy is not advisable and, therefore,
      pharmacologic options are narrowed to dose adjustments, adding adjunctive agents
      to induce weight loss, discontinuation of other adjunctive agents associated with
      weight gain, or changing the antipsychotic medication ("switching"). This article
      reviews the evidence showing that relative to other possible treatment options,
      switching to an antipsychotic with a lower propensity to induce weight gain or
      dyslipidemia can be effective for reversing the weight gain and dyslipidemia
      caused by previous antipsychotic treatment.

PMID- 17539699
TI  - Improving medical care for persons with serious mental illness: challenges and
      solutions.
AB  - A critical step in addressing excess medical morbidity and mortality in persons
      with serious mental illness is to better understand and seek to improve the
      medical care that they receive. Medical quality deficits for persons with serious
      mental illness include problems related to overuse of certain medical services,
      such as emergency room care; underuse of some evidence-based general medical
      services; and misuse, or medical error. The origins of poor quality care for
      persons with mental disorders are rooted in interrelated contributory factors
      from patients, providers, and the medical and mental health care systems. At a
      system level, at least 4 types of separation between mental and medical health
      care may exacerbate the problems for persons with serious mental illnesses: (1)
      geographic (lack of co-located medical and mental health services), (2) financial
      (separate funding streams for medical and mental health services), (3)
      organizational (difficulty in sharing information and expertise across these
      systems), and (4) cultural (providers' focus on particular symptoms or disorders,
      rather than on the patients with those problems). Research studies and
      demonstration programs for improving medical care in this population have spanned
      a continuum of medical provider involvement from psychiatrist and patient
      training to on-site consultation by medical staff, multidisciplinary
      collaborative care approaches, and facilitated linkages between community and
      mental health and medical providers. Ultimately, it will be important to develop,
      test, and implement a range of models for improving the medical care of persons
      with serious mental disorders that are tailored to patients' needs, mental health
      system capacities, and local community resources.

PMID- 17539700
TI  - Implementing practice guidelines: lessons from public mental health settings.
AB  - There is evidence that state-of-the-art psychiatric treatments are not being
      translated into community settings, resulting in the de facto denial of up-to
      date psychiatric care for many Americans with mental illness. Although multiple
      models of evidence-based care exist, little is known about how to disseminate
      information regarding these models to clinicians in real-world practice.
      Suggested solutions have included the use of published practice guidelines, such
      as the American Psychiatric Association Practice Guidelines and the Expert
      Consensus Guidelines, or algorithm-based programs, such as the Texas Medication
      Algorithm Project. Unfortunately, the real-world utility of practice guidelines
      tends to be limited, because their implementation depends entirely on
      practitioner self-motivation. Similarly, the use of algorithm-based programs may
      be limited by their pervasive high specificity, practitioner resistance, and
      various patient misperceptions. Another solution is the implementation of
      evidence-based practices (EBPs), such as the Substance Abuse and Mental Health
      Services Administration (SAMHSA) EBPs. However, states' use of the SAMHSA EBPs
      has been hampered by misalignment of the funding structure, lack of information
      regarding EBPs, high costs to train and supervise staff, staff turnover, and a
      lack of resources. As a result, federal and clinical/professional agencies have
      called for a change in the nation's mental health care delivery system, supplying
      persuasive arguments for the economic and clinical superiority of integrated care
      models. One such model, the Missouri Medical Risk Management (MRM) Program for
      Medicaid Recipients with Schizophrenia, currently assists patients identified as
      being at high risk for adverse medical and behavioral outcomes. Preliminary
      results from the Missouri MRM Program are described.

PMID- 17539701
TI  - Integrating general health care in private community psychiatry practice.
AB  - Persons with serious mental illness represent a special at-risk population, with
      elevated medical comorbidity and mortality rates, mainly due to cardiovascular
      disease. For this reason, the treatment plan for patients with mental illness
      must include the assessment of medical risk factors, beginning at the time of the
      initial psychiatric evaluation. Follow-up assessments should proceed as
      recommended by the Expert Consensus Development Panel convened by the American
      Diabetes Association, the American Psychiatric Association, and other relevant
      specialty organizations. Because the various second-generation antipsychotics
      (SGAs) have unique side effect profiles with respect to cardiometabolic risk
      factors, such as weight gain and dyslipidemia, the selection of an SGA always
      should weigh efficacy versus potential risks. Prior to initiating antipsychotic
      therapy, the psychiatrist should not only explain to the patient the risks of the
      medication and alternative treatments, but also address preventive strategies and
      the importance of monitoring. To help evaluate the patient's response and manage
      SGA-related adverse effects, the psychiatrist should spend considerable time in
      contact with the patient, the patient's family and/or caregivers (as
      appropriate), and the patient's primary care physician. To enhance overall
      patient care, the psychiatrist in private practice should implement procedures to
      ensure adequate patient education and address overall health monitoring.
      Furthermore, the psychiatrist must serve as a patient advocate, actively working
      to foster communication with medical colleagues, especially primary care
      practitioners, and identify resources in the community that facilitate preventive
      health care.

PMID- 17539702
TI  - Understanding neuronal pathways: novel targets for the management of insomnia.

PMID- 17539703
TI  - Mechanisms of sleep induction by GABA(A) receptor agonists.
AB  - Gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the
      mammalian central nervous system. GABA(A) receptors are pentameric complexes that
      function as ligand-gated chloride ion channels. Two types of inhibitory
      neurotransmission are mediated via GABA(A) receptors. Phasic inhibition results
      from the activation of receptors at the synapse by intermittent release of high
      concentrations of GABA from presynaptic terminals. Tonic inhibition, in contrast,
      is mediated by the continuous activation of receptors located outside the
      synaptic cleft by low concentrations of ambient GABA. These "extrasynaptic"
      receptors have a higher affinity for GABA and slower rates of desensitization and
      deactivation than do the classical "synaptic" receptors. A variety of subunit
      families make up GABA(A) receptors; a total of 19 distinct subunits have been
      cloned. This diversity in subunit composition results in substantial anatomical,
      functional, and pharmacologic heterogeneity. Receptors containing the alpha1,
      alpha2, or alpha3 subunits with gamma2 are usually found at synapses and are
      sensitive to benzodiazepines and zolpidem, whereas alpha4 and alpha6 subunits are
      often found with delta and play a role in extrasynaptic receptors (in thalamus
      and dentate), as does the alpha5 subunit (in CA1). The alpha4betadelta receptors
      are insensitive to benzodiazepines and zolpidem, but show high sensitivity to
      other sedative-hypnotic drugs, including ethanol and the novel hypnotic drug
      gaboxadol (THIP). This review will examine the role of heterogeneity of GABA(A)
      receptors, and recent research demonstrating subunit-dependent modulation of
      receptors by novel pharmacologic agents will be discussed.

PMID- 17539704
TI  - A physiologic basis for the evolution of pharmacotherapy for insomnia.
AB  - Insomnia is a highly prevalent disorder with consequences for the patient's
      physical and mental health, daily function, and job performance. Although the
      exact pathophysiology of insomnia is unknown, recent research has demonstrated
      that normal sleep and wakefulness are controlled by reciprocal inhibition by
      different brain regions. This sleep-wake control system offers multiple
      therapeutic targets for the treatment of insomnia; currently, most research and
      available hypnotic agents target gamma-aminobutyric acid (GABA) on the sleep side
      of the switch. Historically, drugs have evolved from benzodiazepine receptor
      agonists to nonbenzodiazepines to, most recently, selective extrasynaptic GABA(A)
      receptor agonists. However, these drugs have a differential impact on
      characteristics of sleep. Among the compounds that modulate the benzodiazepine
      sensitive GABA(A) receptors, benzodiazepines suppress stage 3-4 sleep, whereas
      nonbenzodiazepines have no substantial effect on these stages of sleep. Recently,
      work on GABA agonists indicates that they increase stage 3-4 sleep. This has been
      demonstrated via sleep-stage scoring as well as with spectral analysis. Further,
      this increase in stage 3-4 sleep is associated with a decrease in stage 1 sleep
      and arousals from sleep. Thus, the GABA agonists may not simply promote sleep,
      but consolidate it as well. The clinical utility of the increase in slow-wave
      sleep and the sleep consolidation it produces warrants further investigation.

PMID- 17539705
TI  - Combining pharmacologic and nonpharmacologic therapies for insomnia.
AB  - Although both clinical experience and formal studies confirm the efficacy of
      cognitive-behavioral therapy (CBT) and hypnotic medications as treatments for
      insomnia, the interaction of the 2 treatments when combined has not been fully
      clarified. In principle, they could potentiate each other, not interact at all
      (in which case the benefits would be the sum of the 2 treatments alone), or
      inhibit each other. In this review, I suggest that the weight of available
      evidence indicates that the 2 treatments have a beneficial interaction, but that
      the paucity of data should prevent excessive generalization. It would be
      desirable for future studies to employ newer hypnotics with a range of doses in
      both nightly and p.r.n. administration and to examine comorbid as well as primary
      insomnias. The manner in which the medication is presented to the patient and the
      caregiver's conviction regarding the effectiveness of therapy need to be
      carefully controlled. Studies that consider these issues will need to be
      performed before firmer conclusions can be reached.

PMID- 17539707
TI  - Antimicrobial photodynamic therapy in the non-surgical treatment of aggressive
      periodontitis: a preliminary randomized controlled clinical study.
AB  - BACKGROUND: The treatment of aggressive periodontitis has always presented a
      challenge for clinicians, but there are no established protocols and guidelines
      for the efficient control of the disease. METHODS: Ten patients with a clinical
      diagnosis of aggressive periodontitis were treated in a split-mouth design study
      to either photodynamic therapy (PDT) using a laser source with a wavelength of
      690 nm associated with a phenothiazine photosensitizer or scaling and root
      planing (SRP) with hand instruments. Clinical assessment of plaque index (PI),
      gingival index (GI), bleeding on probing (BOP), probing depth (PD), gingival
      recession (GR), and relative clinical attachment level (RCAL) were made at
      baseline and 3 months after treatment with an automated periodontal probe.
      RESULTS: Initially, the PI was 1.0 +/- 0.5 in both groups. At the 3-month
      evaluation, the plaque scores were reduced and remained low throughout the study.
      A significant reduction of GI and BOP occurred in both groups after 3 months (P
      <0.05). The mean PD decreased in the PDT group from 4.92 +/- 1.61 mm at baseline
      to 3.49 +/- 0.98 mm after 3 months (P <0.05) and in SRP group from 4.92 +/- 1.14
      mm at baseline to 3.98 +/- 1.76 mm after 3 months (P <0.05). The mean RCAL
      decreased in the PDT group from 9.93 +/- 2.10 mm at baseline to 8.74 +/- 2.12 mm
      after 3 months (P <0.05), and in the SRP group, from 10.53 +/- 2.30 mm at
      baseline to 9.01 +/- 3.05 mm after 3 months. CONCLUSION: PDT and SRP showed
      similar clinical results in the non-surgical treatment of aggressive
      periodontitis.

PMID- 17539708
TI  - Clinical field trial examining an implant with a sand-blasted, acid-etched
      surface.
AB  - BACKGROUND: Conventionally, endosseous dental implants have required 3 to 6
      months of uninterrupted healing based on observations for dental implants that
      were characterized by a relatively smooth machined surface. Many studies have
      since demonstrated that implants with a roughened surface resulted in greater
      bone apposition, earlier bone contact, and a stronger bond between the implant
      and the bone, suggesting that implants with roughened surfaces could be loaded
      earlier than 3 to 6 months. Formal clinical studies confirmed that implants with
      rough surfaces can have abutments placed and be loaded occlusally as early as 6
      weeks postplacement. The purpose of this prospective, human clinical
      investigation was to evaluate a large number of implants with a specific rough
      surface (sand-blasted acid-etched [SLA]) placed in everyday practice under
      routine private-practice conditions. METHODS: A prospective, multicenter, human
      clinical observational study was initiated with the goal of recruiting a minimum
      of 500 patients and 800 implants. The implants were to be placed and restored in
      predominantly private-practice settings around the world. Ninety-two
      practitioners in 16 countries agreed to participate, and 86 followed the study
      design. Patients had to be in good health, have sufficient bone to encase the
      implant, and agree to return for recall appointments. Exclusion criteria included
      heavy smoking (>10 cigarettes a day) and bone augmentation procedures at the
      implant site. All implants were two-piece (an abutment was to be placed after 6
      weeks of healing) and were characterized by the presence of a transmucosal
      polished collar. Each implant had an SLA surface. All implants were positioned
      using a non-submerged (single-stage) surgical technique. Survival and success
      rates were calculated by life-table analyses. RESULTS: A total of 706 patients
      were enrolled and 1,406 implants were placed. In the final analyses, 590 patients
      with 990 implants (70.4% of those enrolled) met all inclusion criteria, including
      placement of an abutment and provisional restoration within 63 days of surgical
      placement. The majority of implants were 10 and 12 mm long (78.7%) and were
      placed in type II and III bone (87%). Seventy-three percent of the implants were
      placed in the mandible, and 27% were placed in the maxilla. The cumulative
      survival rate was 99.56% at 3 years and 99.26% at 5 years. The overall success
      rate was 99.12% at 3 years and 97.38% after 5 years. CONCLUSIONS: Under private
      practice conditions, implants with an SLA surface could be placed and restored
      predictably within 6 to 8 weeks. Data from this prospective, multicenter, human
      observational study reinforced the results of more formal clinical studies and
      demonstrated that implants with the SLA surface can be restored in patients in
      approximately half of the time of conventional healing periods.

PMID- 17539709
TI  - Effect of platelet-rich plasma on the healing of intrabony defects treated with
      an anorganic bovine bone mineral and expanded polytetrafluoroethylene membranes.
AB  - BACKGROUND: Regenerative periodontal therapy with a combination of platelet-rich
      plasma (PRP) + an anorganic bovine bone mineral (ABBM) + guided tissue
      regeneration (GTR) has been shown to result in significantly higher probing depth
      reductions and clinical attachment level gains compared to treatment with open
      flap debridement (OFD) alone, ABBM alone, or GTR alone. However, there are no
      data evaluating to what extent the use of PRP may additionally enhance the
      clinical outcome of the therapy compared to treatment with ABBM + GTR. This study
      aimed to clinically evaluate the effect of PRP on the healing of deep intrabony
      defects treated with ABBM and GTR by means of a non-resorbable expanded
      polytetrafluoroethylene (ePTFE) membrane. METHODS: Twenty-four patients with
      advanced chronic periodontal disease and displaying one intrabony defect were
      randomly treated with a combination of either PRP + ABBM + GTR or ABBM + GTR. The
      following clinical parameters were evaluated at baseline and at 1 year after
      treatment: plaque index (PI), gingival index (GI), bleeding on probing (BOP),
      probing depth (PD), gingival recession (GR), and clinical attachment level (CAL).
      The primary outcome variable was CAL. RESULTS: No differences in any of the
      studied parameters were observed at baseline between the two groups. Healing was
      uneventful in all patients. At 1 year after therapy, the sites treated with PRP +
      ABBM + GTR showed a reduction in mean PD from 8.6 +/- 1.7 mm to 3.1 +/- 1.3 mm (P
      <0.001) and a change in mean CAL from 10.3 +/- 1.4 mm to 5.7 +/- 1.6 mm (P
      <0.001). In the group treated with ABBM + GTR, mean PD was reduced from 8.8 +/-
      1.7 mm to 3.1 +/- 1.0 mm (P <0.001), and the mean CAL changed from 10.4 +/- 2.6
      mm to 5.9 +/- 1.8 mm (P <0.001). In both groups, all sites gained > or =3 mm of
      CAL. CAL gains > or =4 mm were measured in 83% (i.e., in 10 of 12 defects) of the
      cases treated with PRP + ABBM + GTR and in 92% (i.e., in 11 of 12 defects)
      treated with ABBM + GTR. No statistically significant differences in any of the
      studied parameters were observed between the two groups at 1-year reevaluation.
      CONCLUSION: Within its limits, the present study has shown that, at 1 year after
      regenerative therapy in periodontal intrabony defects, optimal clinical results
      were obtained with ABBM + GTR with a non-resorbable barrier, with or without the
      addition of PRP.

PMID- 17539710
TI  - Inter-implant bone height changes in anterior maxillary immediate and non
      immediate adjacent dental implants.
AB  - BACKGROUND: The purpose of this study was to evaluate inter-implant bone crest
      height changes between immediate and non-immediate dental implants placed in the
      anterior maxillary region. METHODS: A retrospective study was conducted on
      consecutively treated patients requiring at least two adjacent implants in the
      anterior maxillary region that were placed in the same operation during 1994 to
      2004. Files of 45 healthy patients reporting 200 implants were reviewed. Age,
      gender, smoking status, and implant characteristics (coating and dimensions) were
      recorded. Inter-implant bone measurements were taken on two panoramic radiographs
      from each patient: one after implant placement and the other at the last follow
      up. The distance between adjacent implants was measured at the implant-abutment
      interface (implant platform). RESULTS: Overall, 130 inter-implant gaps were
      found. Follow-up ranged from 8 to 146 months. Two-tailed Pearson correlation
      tests revealed a negative correlation between inter-implant distance and bone
      loss (P = 0.036). Mean peak-crest bone loss for immediate implants was higher
      than for delayed implants (P = 0.026). There was more bone loss when
      hydroxyapatite (HA)-coated implants were used, although no statistical
      significance was observed. No statistically significant difference was found
      between the different locations in the anterior maxilla. No correlation was found
      between patient's age, smoking habits, and bone loss or between follow-up time
      and bone loss. CONCLUSIONS: A negative correlation was found between inter
      implant distance and bone loss at the inter-implant bone crest in the anterior
      maxillary region. Bone loss was small in this study cohort.

PMID- 17539711
TI  - Evaluation of the effect of subgingival placement of chlorhexidine chips as an
      adjunct to scaling and root planing.
AB  - BACKGROUND: The purpose of this 9-month study was to compare the effect of
      scaling and root planing alone (control) to that of scaling and root planing plus
      application of chlorhexidine chips (test). METHODS: Twenty-six subjects having
      two non-adjacent sites in non-molar teeth with probing depth > or =5 mm and
      bleeding on probing participated in this split-mouth trial. At baseline, the
      patients received full-mouth scaling and root planing followed by placement of
      chlorhexidine chips secured by cyanoacrylate at test sites and placement of
      cyanoacrylate alone at control sites. Test sites still > or =5 mm deep at 3 and 6
      months were retreated with renewed chlorhexidine chip application. Recordings of
      bleeding on probing, probing depths, and clinical attachment levels were
      performed at baseline, after 6 weeks, and after 3, 6, and 9 months. RESULTS:
      Improvements of bleeding scores, probing depths and clinical attachment levels
      were observed for both test and control sites at 6 weeks compared to baseline.
      Subsequently, all three measurements remained comparatively stable throughout the
      study. No differences in improvements were found comparing test and control
      sites. CONCLUSION: This study failed to observe any adjunctive effect of
      subgingival placement of chlorhexidine chips after scaling and root planing.

PMID- 17539712
TI  - Subgingival debridement efficacy of glycine powder air polishing.
AB  - BACKGROUND: Glycine powder air polishing (GPAP) has been shown to be
      significantly more effective in reducing the subgingival cultivable microflora in
      shallow periodontal pockets compared to curets and is safe when applied directly
      to root surfaces. The purpose of this study was to assess the subgingival
      debridement efficacy of GPAP in periodontal pockets with various depths. METHODS:
      In each of 60 patients with severe periodontitis, one tooth with a probing depth
      (PD) > or =6 mm was randomly assigned to one of the following interventions: GPAP
      performed in teeth instrumented 3 months earlier (I); GPAP performed in
      previously non-instrumented teeth (NI); or no treatment (control). GPAP was
      performed for 5 seconds per surface. After extraction, teeth were stained with
      0.5% toluidine blue, and subgingival debridement efficacy was assessed. RESULTS:
      Overall, median debridement depth was 2.00 mm in I teeth and 1.86 mm in NI teeth,
      and the median debrided root surface was 49.24% and 45.64%, respectively. In
      anatomic PDs (APDs) of 2 to 3 mm, relative debridement depth (debridement
      depth/APD) ranged from 65% to 80% and 60% to 75% in I and NI teeth, respectively;
      the corresponding values for debrided root surface were 60% to 70% and 50% to
      60%. In control teeth, virtually all subgingival root surfaces were stained.
      Clinical PD measurements were a median of 1.05 mm deeper than APD. CONCLUSION:
      GPAP for 5 seconds per surface is effective in removing most of the subgingival
      biofilm in periodontal pockets with an APD < or =3 mm.

PMID- 17539713
TI  - The additional effect of a dentifrice on the instant efficacy of toothbrushing: a
      crossover study.
AB  - BACKGROUND: Inconclusive evidence exists in the literature with regard to the
      additional (beneficial) mechanical effect of a dentifrice on plaque removal. A
      previous split-mouth study found that a dentifrice did not contribute to plaque
      removal. Because of limitations of the split-mouth model, a crossover design was
      used to evaluate whether a commercially available dentifrice had an additional
      effect on mechanical plaque removal during manual toothbrushing. METHODS: Thirty
      six subjects were given a manual toothbrush and a standard dentifrice. After a 48
      hour plaque accumulation, subjects brushed under supervision with or without a
      dentifrice (total time of 2 minutes) in a 2 x 2 crossover design. RESULTS: Plaque
      reductions were 50% with and 56% without the use of dentifrice. This 6%
      difference was statistically significant (P = 0.034). Explorative analysis showed
      that brushing without a dentifrice was more effective in removing plaque on the
      approximal surfaces. CONCLUSIONS: The use of a dentifrice did not contribute to
      mechanical plaque removal during manual toothbrushing. It seemed that the
      mechanical action provided by the toothbrush was the main factor in the plaque
      removing process.

PMID- 17539714
TI  - Root coverage in isolated gingival recessions using autograft versus allograft: a
      pilot study.
AB  - BACKGROUND: Different surgical techniques have been used to treat gingival
      recessions. This preliminary study compared clinical findings for the treatment
      of isolated gingival defects using a coronally positioned flap associated with a
      subepithelial connective tissue graft or an acellular dermal matrix graft.
      METHODS: Ten subjects with bilateral and comparable Miller Class I or II defects
      were selected. The defects were > or =3.0 mm deep and were assigned randomly to
      the test group, which was treated with a coronally positioned flap associated
      with an acellular dermal matrix, or to the control group, which was treated with
      a coronally positioned flap associated with a subepithelial connective tissue
      graft. Probing depth (PD), clinical attachment level (CAL), gingival recession
      depth (GRD), and width (KT) and thickness (GT) of the keratinized tissue were
      assessed at baseline and 6 months after the surgery. RESULTS: Mean root coverage
      was 50% in the test group (representing a gingival margin shift of 2.1 +/- 0.99
      mm) and 79.5% in the control group (representing a gingival margin shift of 3.5
      +/- 1.20 mm). These results were statistically different on intra- and intergroup
      comparisons (P <0.05). Between-group comparisons revealed statistically
      significantly greater gains in CAL, GRD, and GT in the control group (P < or
      =0.05); no differences were found for PD or KT (P > or =0.05). CONCLUSIONS: The
      coronally positioned flap associated with a subepithelial connective tissue graft
      or an acellular dermal matrix graft was effective in root coverage. However, the
      coronally positioned flap associated with a connective tissue graft provided a
      more favorable clinical outcome. More expanded studies are needed to confirm the
      present findings.

PMID- 17539715
TI  - Clinical evaluation of the supraosseous gingivae before and after crown
      lengthening.
AB  - BACKGROUND: Despite the broad use of crown-lengthening surgery (CLS), there is no
      complete agreement as to the desired amount of exposed sound tooth structure
      needed to accommodate both the restorative needs and the reformation of the
      supraosseous gingiva (SOG). Classically, it has been proposed that approximately
      3 mm of SOG, the amount considered by most to be present before surgery, will be
      reformed after CLS. The purpose of this study was to test the viability of
      transsulcular probing (TSP) and to determine whether the SOG that forms after CLS
      is the same as that measured preoperatively. METHODS: Nineteen patients underwent
      CLS with the surgical tooth acting both as the control and the test site. The SOG
      dimension was measured by TSP before and 6 months after surgery. Stents were used
      as fixed reference points. Intraclass correlations were calculated to test for
      the reliability of TSP measurements versus direct-bone-level (DBL) measurements.
      A Wilcoxon signed-rank test was used to compare the means for the mean buccal,
      mean lingual, and overall mean SOG dimensions at baseline to corresponding
      measurements at 6 months. RESULTS: Intraclass correlation coefficients for TSP
      measures of SOG to DBL measures of SOG ranged from 83.4% agreement to 91.9%
      agreement, with all correlations being highly significant (P <0.001), indicating
      a high degree of agreement between TSP and DBL. The differences in SOG
      dimensions, 6 months after surgery compared to baseline, were as follows: mean
      buccal, 0.51 mm; mean lingual/palatal, 0.61 mm; overall mean, 0.56 mm. These
      differences were significant for all three comparisons (P <0.001, P <0.004, and P
      <0.001, respectively). CONCLUSIONS: TSP is an accurate alternative method to DBL
      in clinically determining SOG dimensions. Six months after CLS, the SOG dimension
      was reduced by 0.51 to 0.61 mm compared to the presurgical measurement, with
      these mean differences being statistically significant.

PMID- 17539716
TI  - Current oral contraceptive status and periodontitis in young adults.
AB  - BACKGROUND: The aim of this study was to investigate the influence of current
      hormonal contraceptive medication on periodontal health in young females.
      METHODS: Fifty women aged 20 to 35 years (mean +/- SD: 29.7 +/- 4.7 years) had a
      comprehensive periodontal examination. Current and previous contraceptive pill
      use was assessed by a questionnaire. Periodontal assessment included plaque
      index, gingival index, probing depth, and attachment level at six sites per
      tooth. The periodontal health of current pill users was compared to that of women
      not taking the pill. RESULTS: Forty-two percent of subjects were taking the
      contraceptive pill at the time of periodontal examination. Current pill users had
      deeper mean probing depths compared to non-users (3.3 mm versus 2.7 mm; P =
      0.006) and more severe attachment loss (2.6 mm versus 1.7 mm; P = 0.015). Pill
      users had more sites with bleeding on probing (44.0% versus 31.1%; P = 0.017).
      CONCLUSION: Current users of oral contraceptives had poorer periodontal health.

PMID- 17539717
TI  - Interviewing self-reported highly anxious patients during periodontal treatment.
AB  - BACKGROUND: Little information exists on highly anxious patients referred for
      periodontal therapy. METHODS: All patients referred for periodontal therapy
      between November 1, 2002 and April 1, 2004 were included in this study. Patients
      who perceived themselves as extremely anxious were interviewed further, and their
      anxiety levels were observed during the various stages of periodontal therapy.
      RESULTS: Twenty-one (19 females and two males, average age, 49.76 years) of 176
      patients (12.1%) reported extreme anticipatory anxiety. The main reasons for
      their anxiety were fear of pain and previous bad experience(s). CONCLUSIONS:
      Average anxiety levels decreased with the progress of the periodontal therapy.
      However, individual responses varied greatly and were unpredictable.

PMID- 17539718
TI  - Serum antibody levels in smoker and non-smoker saudi subjects with chronic
      periodontitis.
AB  - BACKGROUND: Cigarette smoking is a significant risk factor for the initiation and
      progression of periodontal disease. Studies have shown altered serum and gingival
      crevicular fluid inflammatory cytokine profiles, immune cell function, and
      altered proteolytic regulation in smokers. The observations are not consistent,
      and to date, there is no clear mechanism to explain how smoking may affect
      periodontal disease. Hence, the present study was undertaken to assess the
      alterations of serum immunoglobulin levels in smokers with periodontitis and its
      potential role as a risk indicator of the disease process. METHODS: In this
      study, 30 patients who smoked and 30 patients who did not smoke with chronic
      periodontitis and 30 healthy subjects were enrolled. Serum immunoglobulin (Ig) G,
      IgA, and IgM levels were estimated with immunoturbidimetric assay. The IgG
      subclass (IgG1, IgG2, IgG3, and IgG4) levels were performed using single radial
      immunodiffusion assay. RESULTS: Levels of serum IgG and IgA were significantly
      lower in smokers compared to non-smokers and healthy controls (P <0.001).
      Although IgM levels were low in smokers, it was not significant. Of the four
      subclasses of IgG studied, the IgG2 was found to be significantly lower among
      smokers with periodontitis. CONCLUSIONS: Current observations indicate that
      cigarette smoking may be associated with the suppression of B-cell function and
      immunoglobulin production. The alteration of antibody levels further explains the
      potential mechanism by which smoking exacerbates periodontal disease. Further
      studies at the molecular level may highlight the specific mechanism by which
      tobacco can interact with cells of the immune system and its impact on
      periodontal disease process.

PMID- 17539719
TI  - Bacterial species in subgingival plaque and oral bone loss in postmenopausal
      women.
AB  - BACKGROUND: Oral bacteria are widely recognized in the etiology of periodontal
      disease. We investigated the prevalence of subgingival bacterial infection with
      eight species, tested associations between infection and oral bone loss, and
      assessed potential confounding factors and effect modifiers of those associations
      in a large community-based cohort of postmenopausal women. METHODS: A cross
      sectional study of oral health and osteoporosis in 1,256 postmenopausal women
      recruited from the Buffalo, New York Women's Health Initiative Observational
      Study was conducted. Standardized dental radiographs were used to measure
      alveolar crestal height (ACH). Subgingival plaque samples were taken, and the
      presence of eight bacterial species was assessed by indirect immunofluorescent
      microscopy in each participant. RESULTS: The most prevalent infection was
      Streptococcus sanguis (59.5%), followed by Prevotella intermedia (43.4%),
      Tannerella forsythensis (37.9%), Capnocytophaga sp. (36.9%), Eubacterium
      saburreum (32.7%), Campylobacter rectus (17.4%), Porphyromonas gingivalis
      (15.1%), and Fusobacterium nucleatum (14.2%). Infections with P. gingivalis, T.
      forsythensis, P. intermedia, and C. rectus were associated with an increased
      likelihood of having oral bone loss as measured by ACH, even after adjustment for
      age, smoking, and income. The body mass index (BMI) was a modifier of this
      association. Overweight women with T. forsythensis infection were more likely to
      have oral bone loss (OR = 3.37; 95% confidence interval [CI]: 2.08 to 5.46) than
      normal weight (OR = 1.27; 95% CI: 0.82 to 1.98) or obese (OR = 1.26, 95% CI: 0.72
      to 2.20) women with T. forsythensis infection. CONCLUSIONS: The prevalence of
      specific bacterial infections was determined for a large group of postmenopausal
      women. Those with infection were more likely to have oral bone loss. Further
      studies should investigate potential modifying effects of BMI and/or inflammatory
      factors.

PMID- 17539720
TI  - RANKL upregulation associated with periodontitis and Porphyromonas gingivalis.
AB  - BACKGROUND: Receptor activator of nuclear factor-kappa B (NF-kappaB) ligand
      (RANKL) and osteoprotegerin (OPG) are critical for homeostatic control of
      osteoclast activity, suggesting their vital roles in the progression of bone loss
      in periodontitis. In this study, the expression of RANKL and OPG mRNA and the
      relationship between these factors and periodontopathic bacteria in periodontal
      tissue were studied. METHODS: Gingival tissue and subgingival plaque samples were
      collected from 15 patients with chronic periodontitis and 15 periodontally
      healthy subjects. RNA was extracted from the tissue and subjected to reverse
      transcription-polymerase chain reaction (RT-PCR) using primers specific for RANKL
      or OPG. Beta-actin was amplified as a control to ensure equal loading. The
      intensity of RT-PCR products was analyzed by a densitometer in proportion to the
      intensity of beta-actin. The numbers of Porphyromonas gingivalis and
      Actinobacillus actinomycetemcomitans were determined by quantitative real-time
      PCR. RESULTS: Our results showed increased levels of RANKL mRNA in chronic
      periodontitis tissues. The RANKL/OPG expression ratio was significantly higher in
      the periodontitis group compared to the healthy control group (P = 0.001).
      Interestingly, the expression of RANKL (r = 0.64; P <0.001), but not OPG (r = 
      0.24; P = 0.20), was significantly correlated with increased numbers of P.
      gingivalis. A. actinomycetemcomitans was detected in only 6.7% of all sites.
      CONCLUSIONS: Chronic periodontitis was associated with RANKL mRNA upregulation
      and increased RANKL/OPG mRNA expression ratio. In addition, our data showed for
      the first time to our knowledge an association between upregulated RANKL levels
      and the number of P. gingivalis in clinically obtained periodontal tissues.

PMID- 17539721
TI  - Radiographic study of ethnic variation in alveolar bone height among New Zealand
      dental students.
AB  - BACKGROUND: The aim of this study was to determine anatomical variations in the
      radiographic distance between the cemento-enamel junction and the alveolar crest
      with respect to ethnic heritage and gender in New Zealand dental students.
      METHODS: Digitized bitewing films of 123 second-year New Zealand dental students
      were examined with a computer imaging program on a desktop computer screen. The
      race of parents and grandparents was obtained by questionnaire. RESULTS: The mean
      distance from the cemento-enamel junction to the alveolar crest across the sample
      was 0.97 mm. Eighteen (14.6%) of the participants had measurements >2 mm, of whom
      17 were Asians. Asians had a significantly larger mean distance than did non
      Asians (1.10 mm compared to 0.83 mm; P <0.001). Gender was not a significant
      variable. CONCLUSIONS: Students of Asian origin had a significantly greater
      distance between the cemento-enamel junction and the alveolar crest. It remains
      to be determined whether this is anatomical or disease related.

PMID- 17539722
TI  - Periodontal tissue response to coverage of root cavities restored with resin
      materials: a histomorphometric study in dogs.
AB  - BACKGROUND: The purpose of this study was to histomorphometrically evaluate the
      response of periodontal tissues covering Class V resin restorations in dogs.
      METHODS: After raising a mucoperiosteal flap, bony defects measuring 5 x 5 mm
      were created on the buccal aspect of the canines of five dogs followed by cavity
      preparations on the root surface measuring 3 x 3 x 1 mm. Before repositioning the
      flap to cover the bone defect, the cavities were restored with composite resin
      (CR) or resin-modified glass ionomer cement (RMGIC) or were left unrestored as
      control (C). The dogs were euthanized 90 days after surgery. Specimens comprising
      the tooth and periodontal tissues were removed, processed routinely, cut into
      longitudinal serial sections in the buccolingual direction, and stained with
      hematoxylin and eosin (H&E) or Masson's trichrome. The most central sections were
      selected for histomorphometric analysis. RESULTS: Histomorphometric analysis
      revealed apical migration of epithelial tissue onto the restorative materials
      (RMGIC and CR). The C group presented significantly longer connective tissue
      attachment (P <0.05) than the RMGIC and CR groups and significantly higher bone
      regeneration (P <0.05) compared to the RMGIC group. Histologically, the cervical
      third (CT) of all groups had the most marked chronic inflammatory infiltrate.
      CONCLUSIONS: Within the limits of this study, it can be concluded that the
      restorative materials used exhibit biocompatibility; however, both materials
      interfered with the development of new bone and the connective tissue attachment
      process.

PMID- 17539723
TI  - Interleukin-17: a new paradigm in inflammation, autoimmunity, and therapy.
AB  - Chronic diseases, such as periodontal disease (PD) and rheumatoid arthritis (RA),
      are characterized by a robust immune response resulting in unresolved
      inflammation. Inflammation is mediated by proinflammatory cytokines; recently, a
      novel subset of T-helper (Th) cells was identified that plays a crucial role in
      inflammation and autoimmune disease. This population secretes several
      proinflammatory cytokines, including the novel cytokine interleukin (IL)-17, and,
      hence, has been termed "Th17." Inflammatory cytokines are implicated in the
      progression of localized chronic infections, such as PD, and in serious systemic
      pathologies, such as diabetes, chronic obstructive pulmonary disease, and
      cardiovascular disease. IL-17 mediates inflammation through a receptor (IL-17R)
      composed of two subunits, IL-17RA and IL-17RC. Drugs that antagonize inflammatory
      cytokines are used therapeutically to downregulate immune-mediated pathology in
      conditions such as RA, although not all patients respond well to this approach.
      Therefore, identification of potential novel therapeutic targets, such as the IL
      17 signaling complex, may be clinically relevant for mitigating inflammatory
      pathology. However, the manner in which such a therapeutic may influence the
      onset and progression of PD is poorly understood. Therapeutics that antagonize
      inflammatory cytokines ameliorate inflammation and bone loss and may have broader
      implications for individuals with systemic diseases in which inflammation and
      autoimmunity predominate.

PMID- 17539724
TI  - Melatonin: potential functions in the oral cavity.
AB  - BACKGROUND: Melatonin is synthesized and secreted by the pineal gland and other
      organs. The pattern of melatonin secretion is controlled by an endogenous
      circadian timing system and conveys information about the light-dark cycle to the
      organism, thereby organizing its seasonal and circadian rhythms. Melatonin has
      powerful antioxidant effects, functions in an immunomodulatory role, may protect
      against certain cancers, delays some age-related processes, stimulates the
      synthesis of type I collagen fibers, and promotes bone formation. METHODS: An
      extensive review was made (e.g., using PubMed, Science Direct, and Web of
      Knowledge) of the literature. RESULTS: Melatonin, which is released into the
      saliva, may have important implications for dental disorders, especially in
      periodontal disease. Diseases of the periodontium are known to be aggravated by
      free radicals and by alterations in the immune response to microorganisms that
      are present in plaque. In response to periodontal inflammation, the blood and
      salivary levels of melatonin may increase. CONCLUSION: Melatonin may play a role
      in protecting the oral cavity from tissue damage that is due to oxidative stress,
      and it may contribute to the regeneration of alveolar bone through the
      stimulation of type I collagen fiber production and the modulation of
      osteoblastic and osteoclastic activity.

PMID- 17539725
TI  - Influence of sampling strategy on microbiologic results before and after
      periodontal treatment.
AB  - BACKGROUND: The aim of this study was to test whether different sampling
      strategies would influence the microbiologic outcomes by assessing the bacterial
      load and composition of the subgingival microbiota by means of anaerobic
      culturing before and after periodontal treatment. METHODS: The first study (1
      versus 4 [1vs4]) included 33 patients with generalized chronic periodontitis. Two
      sampling strategies were compared, sampling one site from the deepest pocket in
      the mouth (M1) versus a pooled sample of four sites from the deepest pockets in
      each quadrant (M4). The second study (2 versus 4 [2vs4]) included 20 patients
      with generalized chronic periodontitis. The strategy M4 was compared to a pooled
      sample of two non-adjacent sites in the same quadrant (M2). All samples were
      processed identically by means of anaerobic culturing. In both studies, a
      pretreatment sampling was taken. However, in the second study (2vs4), subgingival
      samples were also taken at 1, 3, and 6 months after periodontal therapy.
      Quantitative data were compared between strategies by means of t test and signed
      rank test; qualitative data were compared by means of 2 x 2 contingency tables.
      RESULTS: Pretreatment samples showed that total anaerobic counts were
      significantly higher for M4 compared to M1 (P <0.001) and M2 (P = 0.025).
      However, there were no significant differences in regard to percentage of
      microbiota and counts for each pathogen. Most of the qualitative differences
      between strategies were caused by false negatives in M1 and M2. Post-treatment
      samples showed a reduction in total counts and a limited impact in the frequency
      of detection of periodontal pathogens. M2 detected a significant decrease in the
      frequency of detection of Porphyromonas gingivalis, which was not confirmed by
      the M4 strategy. CONCLUSION: The criteria of selection and the number of sites
      selected when sampling the subgingival biofilm in patients with generalized
      chronic periodontitis may influence the detection and quantitation of periodontal
      pathogens when evaluated by culture especially after treatment.

PMID- 17539726
TI  - Mechanical stress induces osteopontin expression in human periodontal ligament
      cells through rho kinase.
AB  - BACKGROUND: Mechanical stress such as orthodontic forces can produce mechanical
      damage and inflammatory reaction in the periodontium. Osteopontin (OPN) is a
      multifunctional cytokine that has been correlated with periodontal disease
      progression. Because the periodontal ligament (PDL) can be affected by stress and
      PDL cells are involved in periodontal destruction and remodeling, we aimed to
      study the influence of mechanical stress on the expression and regulation of OPN
      in human PDL (HPDL) cells. METHODS: The mechanical stress was generated by
      continuous compressive force, and the expression of OPN was examined by reverse
      transcription-polymerase chain reaction and Western analysis. The application of
      inhibitors was used to examine the mechanism involved. RESULTS: Both mRNA and
      protein expression of OPN significantly increased in a force-dependent manner.
      Increase of receptor activator of nuclear factor-kappa B ligand (RANKL) was also
      observed. Interestingly, application of indomethacin could abolish the induction
      of RANKL but not that of OPN, suggesting the cyclooxygenase-independent mechanism
      for stress-induced OPN expression. In addition, the upregulation of OPN was
      diminished by Rho kinase inhibitor but not by cytochalasin B. CONCLUSIONS:
      Mechanical stress affects OPN expression in HPDL cells through the Rho kinase
      pathway. Because OPN participates in bone resorption and remodeling induced by
      mechanical and biologic signals, these results suggest the significance of stress
      induced OPN in HPDL cells in alveolar bone resorption and remodeling.

PMID- 17539727
TI  - Morphometric, histomorphometric, and microcomputed tomographic analysis of
      periodontal inflammatory lesions in a murine model.
AB  - BACKGROUND: Porphyromonas gingivalis is recognized as one of the major
      periodontal pathogens in chronic periodontitis, a common infectious disease
      characterized by inflammation and destruction of periodontal tissues. Several
      animal models with P. gingivalis have been used in periodontitis studies.
      Additionally, multiple approaches have also been applied to measuring alveolar
      bone loss in periodontitis models, including histomorphometry, morphometry, and
      radiography. The aims of this study were to assess periodontal inflammatory
      lesions after P. gingivalis-induced periodontitis and use this model to compare
      three approaches for assessing alveolar bone loss. METHODS: Twelve-week-old male
      C57BL/6 mice were divided into two groups: 48 P. gingivalis-infected and 52
      untreated control mice. Periodontitis was induced by wrapping P. gingivalis
      soaked ligatures around the left maxillary second molar and changing the
      ligatures every other day. Mice were euthanized on days 0, 3, 7, and 10 after
      ligature placement, for a total of 12 experimental and 13 control mice per time
      point. Epithelial downgrowth, inflammation, and osteoclast activity were
      evaluated; alveolar bone loss was determined by histomorphometry, morphometry,
      and microcomputed tomography. RESULTS: The P. gingivalis-infected group showed
      significantly increased epithelial downgrowth (P <0.05), inflammation (P <0.05),
      alveolar bone loss (P <0.05), and osteoclast activity (P <0.05) throughout the
      experimental period compared to the controls. All three methods yielded efficient
      evaluation of alveolar bone loss. CONCLUSIONS: Our results show evidence that the
      P. gingivalis-soaked ligature-induced murine model mounts an adequate
      inflammatory response and exhibits periodontal tissue breakdown compatible with
      other models of periodontal disease. In addition, alveolar bone loss can
      accurately be quantified using any of the three alveolar bone analyses presented
      in this article.

PMID- 17539728
TI  - The expression of vascular endothelial growth factor in a rat model at
      destruction and healing stages of periodontal disease.
AB  - BACKGROUND: The major role of vascular endothelial growth factor (VEGF), an
      angiogenic mediator, in promoting the progression or the healing of periodontal
      disease is still unclear. The aim of this study was to evaluate the VEGF
      expression in the destruction and healing stages of periodontal disease and to
      investigate the association between VEGF expression and vascularization with
      regard to the number and diameters of blood vessels. METHODS: Thirty rats were
      distributed equally into two test groups and a control group. Experimental
      periodontal disease was induced in the test groups by silk ligatures, which were
      kept in position for 40 days. On the 40th day, ligatures were removed from the
      healing group, whereas ligatures were left in position in the destruction group.
      On the 60th day, rats were sacrificed; histomorphometric and biochemical analyses
      were carried out to determine the number and diameters of blood vessels and the
      assessment of VEGF concentration by enzyme-linked immunosorbent assay,
      respectively. RESULTS: There was a statistically significant increase in the
      number of blood vessels in the healing group and in the diameters of blood
      vessels in the destruction group compared to the control group (P <0.001). In
      vivo VEGF expressions were highest in the healing group (P <0.001) and correlated
      significantly with the number of blood vessels (r(2) = 0.814; P = 0.001).
      CONCLUSION: VEGF expression may be related more to the healing stage of
      periodontal disease than to the destruction stage of the lesion.

PMID- 17539729
TI  - Lysophosphatidic acid modulates the healing responses of human periodontal
      ligament fibroblasts and enhances the actions of platelet-derived growth factor.
AB  - BACKGROUND: Platelet-derived growth factor (PDGF) has been used to promote
      healing in many in vitro and in vivo models of periodontal regeneration. PDGF
      interacts extensively with lysophosphatidic acid (LPA). We recently showed that
      LPA modulates the responses of human gingival fibroblasts to PDGF. The objectives
      of this study were as follows: 1) to evaluate the basic interactions of LPA with
      primary human periodontal ligament fibroblasts (PDLFs) alone and with PDGF-BB for
      promoting PDLF growth and migration; 2) to determine the effects in an in vitro
      oral wound-healing model; and 3) to identify the LPA receptors (LPARs) expressed
      by PDLF. METHODS: PDLF regenerative responses were measured using 1 and 10 microM
      LPA in the absence or presence of 1 or 10 ng/ml PDGF. Cell proliferation was
      determined by 5-bromo-2'-deoxyuridine (BrdU) immunohistochemistry and by cell
      counting. Migration responses were measured using a microchemotaxis chamber.
      PDLFs were grown to confluence on glass slides, a 3-mm-wide wound was
      mechanically inflicted, and wound fill on days 4, 6, and 9 was reported. PDLF
      LPAR expression was determined using Western blotting. RESULTS: PDLFs exhibited
      proliferative and chemotactic responses to LPA; these responses were enhanced
      when LPA and PDGF were present together. LPA plus PDGF elicited complete wound
      fill. PDLFs express the LPARs LPA(1), LPA(2), and LPA(3). CONCLUSIONS: To our
      knowledge, this study provides the first evidence that LPA stimulates human PDLF
      wound healing responses and interacts positively with PDGF to regulate these
      actions. These results suggest that LPA and its receptors play important
      modulatory roles in PDLF regenerative biology.

PMID- 17539730
TI  - Periodontal surgery and glass ionomer restoration in the treatment of gingival
      recession associated with a non-carious cervical lesion: report of three cases.
AB  - BACKGROUND: Buccal gingival recession is a prevalent problem in populations with
      a high standard of oral hygiene and is very often associated with a non-carious
      cervical lesion, complicating treatment. The purpose of this report is to show
      three cases treated by an integrated periodontal and restorative dentistry
      approach. METHODS: Three patients with Miller Class I gingival recessions
      associated with non-carious cervical lesions were enrolled for treatment. One
      patient received a coronally positioned flap and a resin-modified glass ionomer
      restoration, and two patients were treated with a coronally positioned flap,
      resin-modified glass ionomer restoration, and connective tissue graft. Probing
      depth (PD), relative gingival recession (RGR), and clinical attachment level
      (CAL) were measured at baseline and at 6 and 8 months after surgery. RESULTS:
      After the healing period, all patients showed CAL gain and reduction in RGR. No
      difference was observed on PDs compared to baseline. No signs of gingival
      inflammation or bleeding on probing were seen. The patients were satisfied with
      the final esthetics and had no more dentin hypersensitivity. CONCLUSION: This
      report indicates that teeth with Miller Class I gingival recessions associated
      with non-carious cervical lesions can be successfully treated by an integrated
      periodontal and restorative dentistry approach; however, longitudinal randomized
      controlled clinical trials must be performed to support this approach.

PMID- 17539731
TI  - Excessive gingival bleeding in two patients with Glanzmann thrombasthenia.
AB  - BACKGROUND: Glanzmann thrombasthenia (GT) is an exceedingly rare but well-defined
      inherited disorder of platelet function caused by a defect in the glycoprotein
      IIb/IIIa complex. The association of GT with consanguinity has been noted,
      especially in geographic regions in which intermarriage is common. In most
      patients, GT is diagnosed during early infancy or before the age of 5 years.
      Common manifestations of this disorder are gingival hemorrhage, purpura,
      epistaxis, petechiae, and menorrhagia. Chronic, prolonged, untreated, or
      unsuccessfully treated bleeding may be life threatening. METHODS: We report two
      female patients with GT who were referred by our hematology clinic to our
      periodontology department for the treatment of excessive gingival bleeding. The
      first patient was treated with a platelet transfusion and underwent periodontal
      therapy (scaling and root planing and dental polishing). The second patient,
      whose GT was undiagnosed at the time of her referral to our department, applied
      to our emergency service because of uncontrolled gingival bleeding that developed
      after scaling and root planing was performed by her dentist. Both patients had
      been called for regular dental visits. RESULTS: All treated sites healed without
      complications. The first patient was monitored for 2 years, during which she
      practiced proper oral hygiene and experienced no periodontal complications. The
      other patient did not participate in follow-up. CONCLUSIONS: Gingival bleeding is
      usually the first sign of most hematologic disorders, and dentists must be alert
      for the signs of unusual gingival bleeding. In such cases, collaboration with a
      hematologist is essential. Under the proper circumstances, periodontal treatment
      can be performed with an acceptable outcome. With proper oral hygiene, we believe
      that there will be no complications and no gingival bleeding.

PMID- 17539732
TI  - Treatment of gingival overgrowth in a child with Bardet-Biedl syndrome.
AB  - BACKGROUND: Bardet-Biedl syndrome (BBS) is a rare, heterogeneous, autosomal
      recessive condition, primarily characterized by polydactyly, obesity, mental
      retardation, hypogonadism, retinopathy, and renal failure. Dental anomalies,
      regarded as secondary manifestations, include hypodontia, microdontia, short
      roots, and deep palate. Few reports in the literature have described the oral
      manifestations of BBS. This article reports a case of BBS in a boy who presented
      some typical oral manifestations added to a generalized gingival overgrowth, an
      anomaly that had not been reported previously in patients with this syndrome.
      METHODS: A 12-year-old white male presented with a diagnosis of BBS and chief
      complaint of gingival enlargement in the anterior segment of both arcades. The
      treatment plan included surgical removal of the overgrown gingiva followed by
      orthodontic therapy. The excised tissues were submitted to histologic analysis.
      RESULTS: There was no sign of recurrence 1 year after gingivectomy.
      Histopathology revealed a dense connective tissue with a mild inflammatory
      infiltrate, irregularly arranged fiber bundles, and epithelial acanthosis, which
      is characteristic of gingival overgrowth. CONCLUSIONS: The gingival overgrowth
      was treated successfully by gingivectomy. The periodontal surgery minimized the
      functional, social, and emotional consequences of the oral manifestation
      associated with the syndrome.

PMID- 17539733
TI  - Hypoplasminogenemia with ligneous periodontitis: a failed local therapeutic
      approach.
AB  - BACKGROUND: Hypoplasminogenemia is a rare condition that is associated with
      ligneous conjunctivitis, a form of chronic conjunctivitis characterized by firm,
      fibrin-rich, pseudomembranous lesions on the tarsal conjunctivae and oral
      lesions. Pseudomembranes may develop on the gingivae, and there may be
      periodontal involvement. METHODS: Several therapeutic approaches have been
      developed to treat such patients, but they have had limited effect. We used
      gingivectomies, topical heparin, and corticosteroids to treat periodontal lesions
      in an 18-year-old girl. RESULTS: This approach had no benefit. CONCLUSION: The
      question remains about how best to manage patients with hypoplasminogenemia.

PMID- 17539734
TI  - Potential of heterotopic fibroblasts as autologous transplanted cells for
      tracheal epithelial regeneration.
AB  - The tracheal epithelium maintains the health of the respiratory tract through
      mucociliary clearance and regulation of ion and water balance. When the trachea
      is surgically removed, artificial grafts have been clinically used by our group
      to regenerate the trachea. In such cases, the tracheal epithelium needs 2 months
      for functional regeneration. Previous study has shown that fibroblasts facilitate
      tracheal epithelial regeneration. In this study, heterotopic fibroblasts
      originating from the dermis, nasal, and gingival mucosa were cocultured with
      tracheal epithelial cells to evaluate their potential as autologous transplanted
      cells for tracheal epithelial regeneration. The epithelia induced by the
      heterotopic fibroblasts showed differences in structure, cilia development, mucin
      secretion, and expression of ion and water channels. These results indicated that
      nasal fibroblasts could not induce mature tracheal epithelium and that dermal
      fibroblasts induced epidermis-like epithelium. Only the gingival fibroblasts
      (GFBs) could induce morphologically and functionally normalized tracheal
      epithelium comparable to the epithelium induced by tracheal fibroblasts.
      Epithelial cell proliferation and migration were also upregulated by GFBs. These
      results indicate that GFBs are useful as autologous transplant cells for tracheal
      epithelial regeneration.

PMID- 17539735
TI  - Recovery from skeletal fluorosis.

PMID- 17539736
TI  - Urokinase plasminogen activator receptor affects bone homeostasis by regulating
      osteoblast and osteoclast function.
AB  - The uPAR and its ligand uPA are expressed by both osteoblasts and osteoclasts.
      Their function in bone remodeling is unknown. We report that uPAR-lacking mice
      display increased BMD, increased osteogenic potential of osteoblasts, decreased
      osteoclasts formation, and altered cytoskeletal reorganization in mature
      osteoclasts. INTRODUCTION: Urokinase receptor (uPAR) is actively involved in the
      regulation of important cell functions, such as proliferation, adhesion, and
      migration. It was previously shown that the major players in bone remodeling,
      osteoblasts and osteoclasts, express uPAR and produce urokinase (uPA). The
      purpose of this study was to investigate the role of uPAR in bone remodeling.
      MATERIALS AND METHODS: In vivo studies were performed in uPAR knockout (KO) and
      wildtype (WT) mice on a C57Bl6/SV129 (75:25) background. Bone mass was analyzed
      by pQCT. Excised tibias were subjected to mechanical tests. UPAR KO calvaria
      osteoblasts were characterized by proliferation assays, RT-PCR for important
      proteins secreted during differentiation, and immunoblot for activator protein 1
      (AP-1) family members. In vitro osteoclast formation was tested with uPAR KO bone
      marrow monocytes in the presence of macrophage-colony stimulating factor (M-CSF)
      and RANKL. Phalloidin staining in osteoclasts served to study actin ring and
      podosome formation. RESULTS: pQCT revealed increased bone mass in uPAR-null mice.
      Mechanical tests showed reduced load-sustaining capability in uPAR KO tibias.
      uPAR KO osteoblasts showed a proliferative advantage with no difference in
      apoptosis, higher matrix mineralization, and earlier appearance of alkaline
      phosphatase (ALP). Surface RANKL expression at different stages of
      differentiation was not altered. AP-1 components, such as JunB and Fra-1, were
      upregulated in uPAR KO osteoblasts, along with other osteoblasts markers. On the
      resorptive side, the number of osteoclasts formed in vitro from uPAR KO monocytes
      was decreased. Podosome imaging in uPAR KO osteoclasts revealed a defect in actin
      ring formation. CONCLUSIONS: The defective proliferation and differentiation of
      bone cells, coincident with both aberrant expression of transcription factors and
      cytoskeletal organization, are typical uPAR-dependent molecular phenotypes, and
      we have now shown their function in osteoblasts and osteoclasts function in vivo.

PMID- 17539737
TI  - IGF-I receptor is required for the anabolic actions of parathyroid hormone on
      bone.
AB  - We showed that the IGF-IR-null mutation in mature osteoblasts leads to less bone
      and decreased periosteal bone formation and impaired the stimulatory effects of
      PTH on osteoprogenitor cell proliferation and differentiation. INTRODUCTION: This
      study was carried out to examine the role of IGF-I signaling in mediating the
      actions of PTH on bone. MATERIALS AND METHODS: Three-month-old mice with an
      osteoblast-specific IGF-I receptor null mutation (IGF-IR OBKO) and their normal
      littermates were treated with vehicle or PTH (80 microg/kg body weight/d for 2
      wk). Structural measurements of the proximal and midshaft of the tibia were made
      by microCT. Trabecular and cortical bone formation was measured by bone
      histomorphometry. Bone marrow stromal cells (BMSCs) were obtained to assess the
      effects of PTH on osteoprogenitor number and differentiation. RESULTS: The fat
      free weight of bone normalized to body weight (FFW/BW), bone volume (BV/TV), and
      cortical thickness (C.Th) in both proximal tibia and shaft were all less in the
      IGF-IR OBKO mice compared with controls. PTH decreased FFW/BW of the proximal
      tibia more substantially in controls than in IGF-IR OBKO mice. The increase in
      C.Th after PTH in the proximal tibia was comparable in both control and IGF-IR
      OBKO mice. Although trabecular and periosteal bone formation was markedly lower
      in the IGF-IR OBKO mice than in the control mice, endosteal bone formation was
      comparable in control and IGF-IR OBKO mice. PTH stimulated endosteal bone
      formation only in the control animals. Compared with BMSCs from control mice,
      BMSCs from IGF-IR OBKO mice showed equal alkaline phosphatase (ALP)(+) colonies
      on day 14, but fewer mineralized nodules on day 28. Administration of PTH
      increased the number of ALP(+) colonies and mineralized nodules on days 14 and 28
      in BMSCs from control mice, but not in BMSCs from IGF-IR OBKO mice. CONCLUSIONS:
      Our results indicate that the IGF-IR null mutation in mature osteoblasts leads to
      less bone and decreased bone formation, in part because of the requirement for
      the IGF-IR in mature osteoblasts to enable PTH to stimulate osteoprogenitor cell
      proliferation and differentiation.

PMID- 17539738
TI  - Contribution of in vivo structural measurements and load/strength ratios to the
      determination of forearm fracture risk in postmenopausal women.
AB  - Bone structure, strength and load-strength ratios contribute to forearm fracture
      risk independently of areal BMD. INTRODUCTION: Technological and conceptual
      advances provide new opportunities for evaluating the contribution of bone
      density, structure, and strength to the pathogenesis of distal forearm fractures.
      MATERIALS AND METHODS: From an age-sratified random sample of Rochester, MN,
      women, we compared 18 with a distal forearm fracture (cases) to 18 age-matched
      women with no osteoporotic fracture (controls). High-resolution pQCT was used to
      assess volumetric BMD (vBMD), geometry, and microstructure at the ultradistal
      radius, the site of Colles' fractures. Failure loads in the radius were estimated
      from microfinite element (microFE) models derived from pQCT. Differences between
      case and control women were assessed, and the risk of fracture associated with
      each variable was estimated by logistic regression analysis. RESULTS: Given
      similar heights, estimated loading in a fall on the outstretched arm was the same
      in cases and control. However, women with forearm fractures had inferior vBMD,
      geometry, microstructure, and estimated bone strength. Relative risks for the
      strongest determinant of fracture in each of the five main variable categories
      were as follows: BMD (total vBMD: OR per SD change, 4.2; 95% CI, 1.4-12),
      geometry (cortical thickness: OR, 4.0; 95% CI, 1.4-11), microstructure
      (trabecular number: OR, 2.3; 95% CI, 1.02-5.1), and strength (axial rigidity: OR,
      3.8; 95% CI, 1.4-10); the factor-of-risk (fall load/microFE failure load) was 24
      % greater (worse) in cases (OR, 3.0; 95% CI, 1.2-7.5). Areas under ROC curves
      ranged from 0.72 to 0.82 for these parameters. CONCLUSIONS: Bone geometry,
      microstructure, and strength contribute to forearm fractures, as does BMD, and
      these additional determinants of risk promise greater insights into fracture
      pathogenesis.

PMID- 17539739
TI  - Novel mouse model of autosomal semidominant adult hypophosphatasia has a splice
      site mutation in the tissue nonspecific alkaline phosphatase gene Akp2.
AB  - Deactivating mutations in the TNSALP gene cause HPP. Akp2(-/-) mice model severe
      infantile HPP, but there is no model for the relatively mild adult form. Here we
      report on mice with an induced mutation in Akp2 that affects splicing. The
      phenotype of homozygotes mirror aspects of the adult form of HPP. INTRODUCTION:
      Hypophosphatasia (HPP) is a clinically varied skeletal disorder resulting from
      deficiency of tissue nonspecific alkaline phosphatase (TNSALP). Mice lacking Akp2
      model infantile HPP characterized by skeletal hypomineralization, impaired
      growth, seizures, and perinatal mortality. No animal model exists to study the
      less severe forms of the disease that typically present in later life. MATERIALS
      AND METHODS: N-ethyl-N-nitrosourea (ENU) mutagenesis was used to generate mouse
      models of human disease. A mouse with low plasma alkaline phosphatase (ALP)
      activity was identified by our clinical chemistry screen. Its offspring were used
      for inheritance studies and subjected to biochemical, histological, and
      radiological phenotyping. DNA was extracted for mapping and osteoblasts harvested
      for functional studies. RESULTS: We showed semidominant inheritance of the low
      ALP phenotype and mapped the underlying point mutation to Akp2. Affected
      offspring bear the splice site mutation 862 + 5G>A-a hypomorphic allele named
      Akp2(Hpp). The same mutation has been reported in a patient. Akp2(Hpp/+) mice
      have approximately 50% of normal plasma ALP but display no other biochemical or
      skeletal abnormalities. Unlike Akp2(-/-) mice, Akp2(Hpp/Hpp) mice have normal
      initial skeletal development and growth, a normal lifespan and do not have
      seizures. TNSALP is low but detectable in Akp2(Hpp/Hpp) plasma. Osteoblasts
      display approximately 10% of normal ALP activity and reduced intracellular
      inorganic phosphate levels, yet are capable of normal mineralization in vitro.
      TNSALP substrates are significantly elevated in urine (inorganic pyrophosphate
      and phosphoethanolamine) and plasma (pyridoxal 5'-phosphate), whereas plasma
      inorganic pyrophosphate levels are normal. Akp2(Hpp/Hpp) mice develop late-onset
      skeletal disease, notably defective endochondral ossification and bone
      mineralization that leads to arthropathies of knees and shoulders. CONCLUSIONS:
      Akp2(Hpp/Hpp) mice mirror a number of clinical features of the human adult form
      of HPP. These mice provide for the first time an animal model of late onset HPP
      that will be valuable in future mechanistic studies and for the evaluation of
      therapies such as those aimed at HPP.

PMID- 17539740
TI  - The impact of advancing age on P-glycoprotein expression and activity: current
      knowledge and future directions.
AB  - With the progressive ageing of the population, an increasing number of elderly
      patients are being exposed to multiple drugs because of co-existing morbidity
      states requiring pharmacological management. However, the knowledge of the
      effects of ageing on the pharmacokinetics and pharmacodynamics of individual
      drugs is far from being optimal as very few elderly subjects are studied in Phase
      I and II premarketing trials. The efflux transporter P-glycoprotein has recently
      emerged as a major determinant of drug disposition in humans. This review
      discusses the current knowledge about the effects of advancing age on P
      glycoprotein expression and activity. A critical appraisal of the published
      literature and an overview on future research directions are also provided.

PMID- 17539741
TI  - In vitro approaches to investigate mechanism-based inactivation of CYP enzymes.
AB  - Mechanism-based inactivation (MBI) of human drug-metabolising CYP enzymes is an
      important consideration in the preclinical ADME evaluation of new drug
      candidates. In this report, the in vitro approaches used to investigate MBI of
      CYP enzymes are described, with an emphasis on the characterisation required to
      assess potential drug-drug interactions. Recent disparities in MBI data between
      in vitro test systems are also reviewed, highlighting the limitations of
      Escherichia coli-expressed human recombinant CYP in the prediction of drug-drug
      interactions that arise via MBI.

PMID- 17539742
TI  - The fate and effects of xenobiotics in human placenta.
AB  - During past decades, knowledge on placental drug metabolism and mechanisms of
      placental transfer has increased significantly. Most pharmaceutical drugs
      administered during pregnancy cross the placenta to some extent. The important
      properties determining the placental transfer by passive diffusion are molecular
      weight, pK(a), lipid solubility and protein binding. In addition to passive
      diffusion, compounds may cross the placenta via active transfer, facilitated
      diffusion, phagocytosis and pinocytosis. This review gives an update of efflux
      transporter proteins and xenobiotic-metabolizing enzymes that modify the fate and
      effects of drugs in the placenta.

PMID- 17539743
TI  - Indinavir/ritonavir remains an important component of HAART for the treatment of
      HIV/AIDS, particularly in resource-limited settings.
AB  - For over a decade, indinavir has been approved for the treatment of HIV/AIDS;
      however, following the introduction of new protease inhibitors (PIs) with
      improved safety and pharmacologic profiles, its use in developed countries has
      become almost obsolete. In contrast, in resource-limited settings where the
      majority of people living with HIV/AIDS reside, indinavir is part of the most
      affordable PI-based highly active antiretroviral treatment regimen. A major
      drawback of indinavir use is renal toxicity, but low-dose indinavir plus
      ritonavir (400/100 mg) twice daily is both efficacious and tolerable. Similar low
      dosing levels in children have also proven successful, but data in pregnant women
      remains limited. Due to its low cost and proven efficacy indinavir remains a key
      component of HIV/AIDS treatment in resource-limited settings.

PMID- 17539744
TI  - Molecular mechanisms of drug resistance in acute myeloid leukaemia.
AB  - Resistance to chemotherapy in acute myeloid leukaemia is a major obstacle to a
      successful outcome for many patients. Often, there is resistance against a broad
      range of drugs due to multiple, simultaneously active processes. These mechanisms
      include effects on drug influx and efflux, drug activation/inactivation, DNA
      repair mechanisms, altered response of end targets, an altered haematopoietic
      microenvironment and dysfunctional apoptotic pathways. This article reviews the
      factors that determine leukaemic cell chemosensitivity and discusses the
      potential for rationally guided therapy.

PMID- 17539745
TI  - Improving metabolic stability of cancer chemoprotective polyphenols.
AB  - Dietary flavonoids and other polyphenols have the potential to be developed as
      effective food supplements as well as drugs for the prevention, as well as
      treatment of, cancer and other disease conditions. However, their very poor oral
      bioavailability, mainly due to extensive conjugation by glucuronidation and
      sulfation, is a severe limiting factor. First, this review shows the use of a
      simple, commercially available model system, the human hepatic S9 fraction, by
      which metabolic stability can be assessed effectively and accurately. Second,
      permethylation of the polyphenols effectively blocks the metabolic conjugation
      reactions, thereby dramatically increasing both metabolic stability and
      intestinal absorption, while maintaining or even increasing the biologic
      activities. Thus, permethylated polyphenols may have a future as chemoprotective
      agents.

PMID- 17539747
TI  - Drug metabolite profiling and elucidation of drug-induced hepatotoxicity.
AB  - Drug metabolism studies, together with pathologic and histologic evaluation,
      provide critical data sets to help understand mechanisms underlying drug-related
      hepatotoxicity. A common practice is to trace morphologic changes resulting from
      liver injury back to perturbation of biochemical processes and to identify drug
      metabolites that affect those processes as possible culprits. This strategy can
      be illustrated in efforts of elucidating the cause of acetaminophen-,
      troglitazone- and valproic acid-induced hepatic necrosis, microvesicular
      steatosis and cholestasis with the aid of information from qualitative and
      quantitative analysis of metabolites. From a pharmaceutical research perspective,
      metabolite profiling represents an important function because a structure
      activity relationship is essential to rational drug design. In addition, drugs
      are known to induce idiosyncratic hepatotoxicity, which usually escapes the
      detection by preclinical safety assessment and clinical trials. This issue is
      addressed, at present, by eliminating those molecules that are prone to metabolic
      bioactivation, based on the concept that formation of electrophilic metabolites
      triggers covalent protein modification and subsequent organ toxicity. Although
      pragmatic, such an approach has its limitations as a linear correlation does not
      exist between toxicity and the extent of bioactivation. It may be possible in the
      future that the advance of proteomics, metabonomics and genomics would pave the
      way leading to personalized medication in which beneficial effect of a drug is
      maximized, whereas toxicity risk is minimized.

PMID- 17539748
TI  - The use of glutathione transferase-knockout mice as pharmacological and
      toxicological models.
AB  - ADME/Tox studies are of increasing importance because of the necessity to
      eliminate poor drug candidates early in the development pipeline. The glutathione
      S-transferases (GSTs) are a family of phase II enzymes that have been shown to
      play a significant role in the disposition of a wide range of drugs and other
      xenobiotics. Several GST-knockout mice strains have been developed that can
      potentially be used in ADME/Tox studies. So far, mice have been generated with
      deficiencies of mGSTP1/2, mGSTA4-4, mGSTZ1-1, mGSTM1-1, mGSTO1-1 and mGSTS1-1,
      but studies of drug metabolism in these strains have been limited. As there are
      21 recognised GST genes in mice there is potential for many more strains to be
      made. However, a review of the available data suggests that because of
      differences in the evolution of the GST gene family between rodents and humans,
      only some knockout strains can provide insights relevant to human drug
      metabolism. It is concluded that, of the strains generated so far, only those
      deficient in mGSTP1-1, mGSTA4-4, mGSTO1-1 and mGSTZ1-1 have direct human
      orthologues and can be considered as human models. In contrast, there may not be
      appropriate orthologues of some enzymes, such as hGSTM1-1, that are known to be
      of relevance in drug metabolism.

PMID- 17539746
TI  - Natural polyphenol disposition via coupled metabolic pathways.
AB  - A major challenge associated with the development of chemopreventive polyphenols
      is the lack of bioavailability in vivo, which are primarily the result of coupled
      metabolic activities of conjugating enzymes and efflux transporters. These
      coupling processes are present in disposition tissues and organs in mammals and
      are efficient for the purposes of drug metabolism, elimination and
      detoxification. Therefore, it was expected that these coupling processes
      represent a significant barrier to the oral bioavailabilities of polyphenols. In
      various studies of this coupling process, it was identified that various
      conjugating enzymes such as uridine 5'-diphosphate-glucuronosyltransferase and
      sulfotransferase are capable of producing very hydrophilic metabolites of
      polyphenols, which cannot diffuse out of the cells and needs the action of efflux
      transporters to pump them out of the cells. Additional studies have shown that
      efflux transporters, such as multi-drug resistance-associated protein 2, breast
      cancer-resistant protein and the organic anion transporters, appear to serve as
      the gate keeper when there is an excess capacity to metabolise the compounds.
      These efflux transporters may also act as the facilitator of metabolism when
      there is a product/metabolite inhibition. For polyphenols, these coupled
      processes enable a duo recycling scheme of enteric and enterohepatic recycling,
      which allows the polyphenols to be reabsorbed and results in longer than expected
      apparent plasma half-lifes for these compounds and their conjugates. Because the
      vast majority of polyphenols in plasma are hydrophilic conjugates, more research
      is needed to determine if the metabolites are active or reactive, which will help
      explain their mechanism of actions.

PMID- 17539749
TI  - Transdermal oxybutynin: a review.
AB  - Overactive bladder is a common and disabling problem. The mainstay of
      pharmacological treatment is with oral anticholinergic drugs. Anticholinergic
      side effects are common and include dry mouth and constipation. Compliance is
      limited by these side effects. Transdermal administration of oxybutynin has been
      shown to be as effective as oral treatment while minimising the anticholinergic
      side effects. Skin reactions occur frequently, necessitating changes of
      application site. Despite this, the preparation is a useful element in the
      armamentarium to treat overactive bladder. It is likely to be particularly useful
      in those in whom side effects of oral medication are intolerable or in whom oral
      administration of drug is not possible. Here, the pharmacokinetics,
      pharmacodynamics, efficacy and safety of transdermal oxybutynin are reviewed.

PMID- 17539750
TI  - Ezetimibe: an update on the mechanism of action, pharmacokinetics and recent
      clinical trials.
AB  - Elevated serum cholesterol is a known risk factor for the development of coronary
      artery disease. Circulating cholesterol is a product of both cholesterol
      absorption from the gut and cellular cholesterol production. Ezetimibe is a novel
      cholesterol-lowering drug that acts at the brush border of the small intestine.
      Recent studies have further identified the molecular target as the Niemann-Pick
      C1-like transporter. Ezetimibe blocks the absorption of dietary and biliary
      cholesterol and plant sterols resulting in intracellular cholesterol depletion.
      Clinical studies have demonstrated beneficial improvements in the lipid profile
      with ezetimibe as monotherapy, but dramatic effects are seen when ezetimibe is
      combined with other lipid-lowering drugs, particularly 3-hydroxy-3-methylglutaryl
      coenzyme A reductase inhibitors (statins). Combination studies of ezetimibe with
      statins, bile acid sequestrants, fenofibrate and niacin all demonstrate
      significant total and low density lipoprotein cholesterol lowering. An excellent
      safety and tolerability profile combined with once-daily dosing make this
      attractive adjunct therapy for the treatment of hypercholesterolemia.

PMID- 17539751
TI  - Chronic sildenafil in men with diabetes and erectile dysfunction.
AB  - Erectile dysfunction frequently represents a neurovascular complication of
      diabetes mellitus, and it has been calculated that almost 50% of diabetic men
      will have erectile dysfunction within 6 years after diagnosis. Penile endothelial
      and smooth muscle cell dysfunction are due to molecular pathway abnormalities
      (i.e., activation of PKC, increased oxidative stress and overproduction of
      advanced-glycosylation end products). The response rate to oral drug therapies,
      such as sildenafil, is lower than in most other groups. Because therapeutic
      alternatives (i.e., intracavernous injections with vasoactive agents) are not
      curative, clinical trials aimed to demonstrate rehabilitative effects with daily
      phosphodiesterase type-5 inhibitors are ongoing. If this approach proves
      successful, it will determine many advantages over the intracavernosal treatment
      and potentially induce sexual rehabilitation.

PMID- 17539752
TI  - Structure and mechanism of cadherins and catenins in cell-cell contacts.
AB  - Cadherins are Ca(2+)-dependent cell adhesion molecules found in several kinds of
      cell-cell contact, including adherens junctions and desmosomes. In the presence
      of Ca(2+), cells expressing the same type of cadherin form stable contacts with
      one another, a phenomenon designated homophilic, or homotypic, adhesion. Most
      cadherins are single-pass transmembrane proteins whose extracellular regions
      mediate specific cell-cell interactions. The intracellular faces of these
      contacts are associated with the actin cytoskeleton in adherens junctions or the
      intermediate-filament system in desmosomes. The close coordination of the
      transmembrane adhesion molecules with the cytoskeleton is believed to be
      essential in coordinating morphogenetic movements of tissues during development
      and in conferring the appropriate mechanical properties to cell-cell contacts.
      Structural, biochemical, and biophysical analysis of the molecules that comprise
      these contacts has provided unique mechanistic insights into the specificity of
      homophilic adhesion, the functional connection to the underlying cytoskeleton,
      and the dynamics of junction formation.

PMID- 17539753
TI  - Semaphorin regulation of cellular morphology.
AB  - Semaphorin proteins, although initially characterized as repulsive neuronal
      guidance cues, are now appreciated as major contributors to morphogenesis and
      homeostasis for a wide range of tissue types. Semaphorin-mediated long- and short
      range repulsive, and attractive, guidance has profound influences on cellular
      morphology. The diversity of semaphorin receptor complexes utilized by various
      semaphorin ligands, the ability of semaphorins themselves to serve as receptors,
      and the myriad of intracellular signaling components that comprise semaphorin
      signaling cascades all contribute to cell-type-specific responses to semaphorins.
      Analysis of the molecular and cellular mechanisms underlying semaphorin function
      in neural and vascular systems provides insight into principles governing how
      this large protein family contributes to organogenesis, function, and disease.

PMID- 17539755
TI  - Orthopaedic Surgery Chief Resident - Grand Rounds Presentations.

PMID- 17539754
TI  - Embryonic patterning in Arabidopsis thaliana.
AB  - Early embryonic development in the flowering plant Arabidopsis thaliana follows a
      predictable sequence of cell divisions. Anatomical hallmarks and the expression
      of marker genes in dynamic patterns indicate that new cell fates are established
      with virtually every round of mitosis. Although some of the factors regulating
      these early patterning events have been identified, the overall process remains
      relatively poorly understood. Starting at the globular stage, when the embryo has
      approximately 100 cells, the organization of development appears to be taken over
      by programs that regulate postembryonic patterning throughout the life cycle.

PMID- 17539756
TI  - Surgical approaches in total hip arthroplasty: a review of the mini-incision and
      MIS literature.
AB  - Modern advances in total hip arthroplasty have included improved biomaterials,
      alternative bearings, so-called fourth-generation cement techniques, and enhanced
      in-growth prostheses. Recently, much attention has been focused on improving the
      surgical technique for total hip arthroplasty. This endeavor has included the
      development of mini-incision arthroplasty and has now progressed to minimally
      invasive procedures. Minimally invasive techniques are modified versions of the
      classic approaches to the hip, with the goal of decreasing soft tissue dissection
      and trauma. While these new surgical exposures may result in improved short-term
      outcomes, their long-term results have yet to be proven. In addition, they are
      technically demanding, may require specialized training, and can be associated
      with a difficult learning curve. Only the future will determine if mini-incision
      and minimally invasive arthroplasty are as successful as the well-proven standard
      surgical approaches used for the last three to four decades.

PMID- 17539757
TI  - Decision making in the treatment of hallux valgus.
AB  - The surgeon must determine the pathologic elements that need correction. Close
      observation for an increased HV angle, increased IM angle, pronation of the first
      toe, increased DMAA, enlarged medial eminence, and subluxation of the sesamoids
      must be performed. While there are a large number of procedures available for the
      management of HV, no one method sufficiently corrects all HV deformities. The
      upper limits of deformity correction for each procedure vary with the surgeon and
      their familiarity with each procedure. Ultimately, the surgeon must attempt to
      maintain a flexible first MTP joint and preserve the normal weightbearing pattern
      of the forefoot. Patient education also can be assistive in avoiding aggravating
      activities and making better choices in shoe wear. Tracings of the weightbearing
      foot and the shoe can be used to demonstrate to patients the size differences
      between the natural size and shape of the foot and that of the shoe, both pre-
      and postoperatively.

PMID- 17539758
TI  - The stiff elbow.
AB  - Etiologies of elbow contractures can be classified into intrinsic versus
      extrinsic causes. Posttraumatic elbow stiffness is the most common intrinsic
      cause and HO formation is the most common extrinsic cause of elbow contractures.
      Patients who sustain significant elbow trauma and have one or more risk factors
      for HO formation should be given prophylaxis against HO formation in the form of
      either indomethacin or radiation therapy. Early excision of HO has been shown to
      be safe and effective. Nonoperative measures are most effective if used within 6
      months of contracture onset. These measures include physical therapy and an
      aggressive splinting program. If nonoperative measures are unsuccessful and the
      patient has functionally limiting elbow ROM, then surgical intervention should be
      considered. Careful preoperative assessment of the ulnar nerve is mandatory, as
      it may need to be transposed. Satisfactory results have been reported with
      arthroscopic elbow contracture releases. However, this procedure is technically
      challenging, with the potential for serious neurovascular complications.
      Satisfactory results have been published for open procedures as well. The
      direction of the greatest limitation of motion, the presence of ulnar nerve
      dysfunction, and the location of osteophytes all help to dictate which surgical
      approach should be selected.

PMID- 17539759
TI  - Adjacent segment degeneration following spinal fusion for degenerative disc
      disease.

PMID- 17539760
TI  - Orthopaedic manifestations of Gaucher disease.
AB  - Gaucher disease is a rare, hereditary disease caused by lack of a lysosomal
      enzyme. This results in the accumulation of glucocerebroside in the cells of the
      reticuloendothelial system, including the bone marrow. The orthopaedic
      manifestations of this disease are important for the orthopaedic surgeon to
      recognize and understand. Patients with Gaucher disease are at risk for
      pathologic fracture, abnormal bony remodeling and delayed healing, increased
      intraoperative bleeding, and infection. Osteomyelitis and avascular necrosis, two
      common sequelae of the disease, can present in very similar fashions and warrant
      careful and accurate diagnosis to ensure proper treatment. The impact of Gaucher
      disease on the musculoskeletal system is reviewed with emphasis on the importance
      of understanding these effects for the treating orthopaedic surgeon.

PMID- 17539761
TI  - Elbow arthroscopy.

PMID- 17539762
TI  - Articular cartilage restoration of the knee.
AB  - Articular cartilage defects are common and play a significant role in
      degenerative joint disease. Cartilage is unable to regenerate, secondary to an
      inherent lack of vascular supply, thus, various techniques have been described in
      an attempt to treat and potentially restore these defects. Treatment decisions
      should be based on appropriate evaluation and classification of the pathology.
      Only then can the surgeon choose to perform a repair or a restoration of the
      articular surface. Current literature and techniques for the treatment of
      articular cartilage defects are reviewed, with an algorithm developed for the
      management of articular cartilage defects by orthopaedic surgeons.

PMID- 17539763
TI  - Elbow arthritis.
AB  - Patients with elbow arthritis typically present with complaints of pain and
      stiffness. Rheumatoid arthritis is the most common cause of elbow arthritis,
      followed by posttraumatic arthritis and primary osteoarthritis. Nonoperative
      management consisting of oral analgesics, intra-articular steroid injections,
      physical therapy, and splinting may provide symptomatic relief in the majority of
      patients. If these modalities fail, operative treatment is guided by the severity
      of disease as well as several patient-related factors such as age, activity
      level, and expectations. Total elbow arthroplasty can provide satisfactory
      results in the majority of patients with significant degeneration of the elbow.
      However, due to issues regarding prosthesis longevity, this procedure is
      generally avoided in young active patients. Other operative treatment options for
      such patients include arthroscopic or open synovectomy, debridement arthroplasty,
      and interpositional arthroplasty. As all of these operations may provide a
      satisfactory outcome for the appropriate patient, a thorough preoperative
      evaluation is essential in choosing the suitable surgical procedure for each
      individual patient.

PMID- 17539764
TI  - High-altitude illness and muscle physiology.
AB  - High-altitude illness is a growing concern in sports medicine that affects
      persons shortly after they have climbed to a new high-altitude level to which
      their body is not acclimatized. With the increasing popularity of extreme sports,
      such as high-altitude mountaineering, skiing, and snowboarding, the incidence of
      complications arising from sports activities at high altitudes is increasing.
      High-altitude pulmonary edema and high-altitude cerebral edema are potentially
      fatal conditions. The study of high-altitude muscle physiology has broad
      ramifications in creating training programs for elite endurance athletes. A
      thorough understanding of the pathophysiology, presentation, treatment, and
      prevention of high-altitude illness is necessary for the treatment of these
      patients.

PMID- 17539765
TI  - Newest advances in the operative treatment of basal joint arthritis.
AB  - Osteoarthritis of the basal joint of the thumb is common, particularly in
      postmenopausal females, and can cause considerable pain and disability.
      Incompetence of the volar beak ligament is thought to be the inciting event that
      eventually leads to joint degeneration in a predictable pattern. The clinical
      history and examination can reliably lead to the diagnosis. Radiographs are used
      to stage the severity of the arthritis. Conservative treatment can be effective
      in early disease. Operative treatment has been shown to be successful in
      relieving pain and restoring thumb function in advanced disease. The majority of
      reconstructive procedures include partial or complete trapeziectomy with beak
      ligament reconstruction and tendon interposition. Secondary metacarpophalangeal
      joint hyperextension and associated carpal tunnel syndrome must be diagnosed and
      addressed to prevent poor outcomes.

PMID- 17539767
TI  - Information for Subscribers and Advertisers.

PMID- 17539766
TI  - Sagittal and coronal biomechanics of the knee: a rationale for corrective
      measures.

PMID- 17539772
TI  - Recent advances into the understanding of mesenchymal stem cell trafficking.
AB  - The use of adult stem cells to regenerate damaged tissue circumvents the moral
      and technical issues associated with the use of those from an embryonic source.
      Mesenchymal stem cells (MSC) can be isolated from a variety of tissues, most
      commonly from the bone marrow, and, although they represent a very small
      percentage of these cells, are easily expandable. Recently, the use of MSC has
      provided clinical benefit to patients with osteogenesis imperfecta, graft-versus
      host disease and myocardial infarction. The cellular cues that enabled the MSC to
      be directed to the sites of tissue damage and the mechanisms by which MSC then
      exert their therapeutic effect are becoming clearer. This review discusses the
      relative therapeutic importance of the ability of MSC to differentiate into
      multiple cell lineages or stimulate resident or attracted cells via a paracrine
      mode of action. It also reviews recent findings that MSC home to damaged tissues
      in a similar, but somewhat distinct, manner to that of leucocytes via the
      utilisation of adhesion molecules, such as selectins and integrins, and
      chemokines and their receptors in a manner reminiscent of leucocytes trafficking
      from the blood stream to inflammatory sites.

PMID- 17539773
TI  - MicroRNAs and haematology: small molecules, big function.
AB  - MicroRNAs are a recently discovered class of small ( approximately 22nt)
      endogenously expressed translational-repressor RNAs that play key roles in many
      cellular pathways and whose aberrant expression appears to be a common feature of
      malignancy. MicroRNAs are expressed in specific haematological cell types and
      play important regulatory roles in early haematopoietic differentiation,
      erythropoiesis, granulocytosis, megakaryocytosis and lymphoid development.
      Additionally, there is an emerging body of research to suggest that microRNAs
      play an important role in the pathology of haematological malignancies. MicroRNAs
      have been found to act as both tumour suppressor molecules [e.g. MIRN15A (miR
      15a), MIRN16-1 (miR-16-1)] in leukaemias and have oncogenic properties [e.g.
      MIRN155 (miR-155) and MIRN17-92 (miR-17-miR-92) cluster] in lymphomas. This
      review discusses the rapidly accumulating research that points to the major role
      microRNAs play in both haematopoiesis and haematological malignancy.

PMID- 17539774
TI  - Advances in the understanding of susceptibility to treatment-related acute
      myeloid leukaemia.
AB  - Treatment-related acute myeloid leukaemia (t-AML) is a devastating complication
      following exposure to the cytotoxic and genotoxic agents used to treat a primary
      malignancy. Whilst the incidence of t-AML is rising, it still only occurs in a
      minority of patients who have received chemotherapy and/or radiotherapy treatment
      and hence it is important to identify factors that may confer susceptibility to
      the development of the condition. This paper reviews the literature and discusses
      the advances and limitations in our understanding of susceptibility factors to t
      AML. In particular, it concentrates upon genetic polymorphisms in detoxification
      genes and in genes belonging to the major DNA repair pathways. This review also
      considers more novel susceptibility factors, such as those proposed to determine
      stem cell number. Increased understanding of t-AML susceptibility may enable
      steps to be taken to prevent its development and increase the effectiveness of
      treatment of the disease.

PMID- 17539775
TI  - Leukaemia-related gene expression in bone marrow cells from patients with the
      preleukaemic disorder Shwachman-Diamond syndrome.
AB  - Shwachman-Diamond syndrome (SDS) is an inherited bone marrow failure disorder
      with cytopenia and a high propensity for myelodysplastic syndrome (MDS) and
      leukaemia, particularly acute myeloid leukaemia. The mechanism of leukaemogenesis
      in SDS is unknown. In accordance to the multi-hit theory of carcinogenesis, it is
      likely that several molecular and cellular hits occur before MDS/leukaemia become
      apparent. This study used oligonucleotide microarray to identify gene expression
      patterns, which were shown to be associated with leukaemogenesis, in marrow
      mononuclear cells of nine SDS patients without overt transformation compared to
      healthy controls. Among 154 known leukaemia-related genes, several oncogenes were
      found to be upregulated, including LARG, TAL1 and MLL, and of several tumour
      suppressor genes were downregulated, including DLEU1, RUNX1, FANCD2 and DKC1.
      Real time polymerase chain reaction confirmed statistically higher expression of
      LARG and TAL1 in SDS marrows. We conclude that SDS marrow mononuclear cells
      exhibit abnormal gene expression patterns, which might result in continuous
      stimulation favouring evolution or progression of malignant clones. Additional
      molecular and cytogenetic events are probably necessary for the malignant process
      to be irreversible and complete.

PMID- 17539776
TI  - High serum levels of B-lymphocyte stimulator are associated with clinical
      pathological features and outcome in classical Hodgkin lymphoma.
AB  - B-lymphocyte stimulator (BLyS) acts as survival factor for B lymphocytes. As
      Hodgkin and Reed-Sternberg (HRS) cells express receptors through which BLyS
      promotes their growth and chemotherapy resistance, we investgated whether this
      molecule was increased in sera from patients with classical Hodgkin lymphoma
      (cHL) and whether it correlates with clinical-pathological features and outcomes.
      Enzyme-linked immunosorbent assay was used to measure soluble BLyS (sBLyS) in
      sera from 87 patients and 33 donors; higher levels were detected in patients
      (mean +/- standard error 4493.9 +/- 264.9 pg/ml vs. 2687.0 +/- 200.9 pg/ml; P <
      0.0001). Levels above the median value (4242.0 pg/ml) were associated with age >
      or = 45 years (P = 0.042), advanced stages of disease (P = 0.005), systemic
      symptoms (P = 0.014) and extranodal involvement (P = 0.009). Five-year failure
      free survival (FFS) of patients with sBLyS below or equal to median levels was
      88.6% as compared to 65.1% of those with levels above the median (P = 0.009).
      Statistical analyses confirmed the prognostic significance of sBLyS (P = 0.046).
      When patients were analysed according to variables associated with high levels,
      sBLyS showed an independent predictive power in terms of FFS. Our findings
      support the involvement of BLyS in cHL pathogenesis. The association between high
      serum levels and an inferior FFS indicates that sBLyS is a possible prognostic
      predictor with a potential significance as a therapeutic target.

PMID- 17539777
TI  - A familial platelet function disorder associated with abnormal signalling through
      the glycoprotein VI pathway.
AB  - The platelet collagen receptor, glycoprotein (GP)VI, of the immunoreceptor family
      forms a complex with the von Willebrand factor (VWF) receptor, GPIb-IX-V,
      critical for initiating thrombus formation. GPVI is co-associated with Fc
      receptor gamma-chain (FcRgamma), which contains a cytoplasmic immunoreceptor
      tyrosine-based activation motif domain, involved in activation of Syk, and a
      signalling cascade leading to (i) activation of alpha(IIb)beta(3), which binds
      VWF and fibrinogen and mediates platelet aggregation, and (ii) metalloproteinase
      mediated shedding of the GPVI ectodomain (blocked by Syk inhibitors), a key
      mechanism for regulating GPVI surface expression. In this study, we report a
      familial case of abnormal platelet aggregation with dysfunctional signalling
      through GPVI that uniquely demonstrates divergent alpha(IIb)beta(3)-activating
      and GPVI-shedding pathways. The patient is a 60-year-old female with a history of
      immune disorders, excessive bleeding from childhood and a life-threatening
      haemorrhage post-trauma. Platelet aggregation to ADP, thrombin receptor-agonist
      peptide or ristocetin/VWF was normal (indicating normal expression and function
      of alpha(IIb)beta(3)), but platelet aggregation to GPVI agonists, collagen,
      collagen-related peptide, or convulxin, was defective. Both GPVI/FcRgamma
      expression and ligand-induced GPVI ectodomain shedding were normal, confirming
      expression of functional GPVI/FcRgamma, but suggesting a signalling defect
      downstream of Syk. A genetic defect in GPVI/Fcgamma signalling compromising
      platelet function is hypothesised in this family.

PMID- 17539778
TI  - Ophthalmology and trends in medical education.

PMID- 17539779
TI  - How might we halve the risk of endophthalmitis?

PMID- 17539780
TI  - Changes in eye care utilization following an eye health promotion campaign.
AB  - BACKGROUND: The Vision Initiative is a public health campaign that promotes the
      early detection of the main causes of vision loss through regular eye
      examinations. Target groups are people over 50 years, with diabetes, a family
      history of glaucoma or age-related macular degeneration and those who have noted
      a change in vision. METHODS: In 2005, a range of initiatives promoted the main
      campaign messages using metropolitan and regional television, radio and
      newspapers. Campaign outcomes such as last visits to an eye specialist were
      evaluated comparing pre- and post-campaign data. Participation was volunteer
      based from randomly selected Melbourne suburbs. Recruitment was by mail.
      Participants were between 70 and 79 years of age. A questionnaire collected
      information about demographics, utilization of eye care services, general health
      and lifestyle. Key features of the five main eye diseases that cause vision loss
      in Australia were assessed. RESULTS: The percentage of people that reported to
      have visited an eye specialist within the last year increased significantly from
      61% to 70% (P<0.001). Also the percentage of people with diabetes that reported
      to have a dilated fundus examination within the last 2 years increased
      significantly from 52% to 70% (P<0.001) and the percentage of people reporting to
      always wear sunglasses when going out in the sun increased significantly from 33%
      to 39% (P<0.001). CONCLUSIONS: Following the campaign, there was an improvement
      in the utilization of eye care services, especially by people with diabetes.
      However, other Australian public campaigns may contribute to the increased
      awareness of the effect of diabetes on eye health.

PMID- 17539781
TI  - Teaching of ophthalmology in undergraduate curricula: a survey of Australasian
      and Asian medical schools.
AB  - BACKGROUND: Despite established international guidelines on preferred teaching
      components for ophthalmology in undergraduate curricula, with increasingly less
      specialty-based undergraduate teaching within curricula, teaching of core
      ophthalmology knowledge and skills may become marginalized. This survey aims to
      evaluate the current state of undergraduate ophthalmology teaching in Australasia
      and proximate Asian medical schools. METHODS: A questionnaire was developed to
      determine the content and extent of ophthalmology teaching in the undergraduate
      medical curriculum. The questionnaire was sent to 25 medical schools throughout
      Australasia and Asia. RESULTS: Nineteen of the 25 questionnaires were returned
      (76% response rate). Ophthalmology teaching programmes ranged from 2 to 20 days:
      five (26%) medical schools having one ophthalmology attachment; six schools (32%)
      two attachments; and the remainder three or more. Only seven of the schools
      taught all 13 ophthalmology topics recommended in current curriculum guidelines.
      Ocular examination (100%), lens and cataract (95%) and ocular manifestations of
      systemic disease (95%) were the most commonly taught topics, with intraocular
      tumours only covered by 10 schools (53%). Students in 14 schools (74%) attended
      ophthalmology operating theatre, but only two schools (11%) offered attendance at
      optometry clinics. Ten schools (53%) required a pass in ophthalmology to complete
      the academic year. CONCLUSION: Ophthalmology may increasingly be a small, or even
      absent, component of undergraduate medical curricula. Despite established
      international ophthalmology curriculum guidelines, this survey highlights
      significant lack of uniformity in their implementation.

PMID- 17539782
TI  - Differences in practice and personal profiles between male and female
      ophthalmologists.
AB  - PURPOSE: To assess practice profiles and attitudes towards career and family
      among ophthalmologists in Australia and New Zealand, with an emphasis on
      identifying gender differences. METHODS: A 43-part confidential survey addressing
      professional and personal issues was sent to all female ophthalmologists and to
      randomly selected age-matched male ophthalmologists, registered with the Royal
      Australian and New Zealand College of Ophthalmologists in 2005. RESULTS: A total
      of 254 (75%) of the surveys were returned, with no significant difference in
      response rate between genders. Differences in practice profiles were identified:
      females preferentially practise in the city (89.6% vs. 76.1%, P<0.001), work
      fewer hours (70% of males working 40 hours per week, compared with 41% of
      females, P<0.0001) and work part time (57.5% vs. 13.6%, P<0.0001). Female
      ophthalmologists earn less (average income being NZ/Aus$37,913 [95% confidence
      interval 25,600-50,226] less, P<0.0001); the difference remained significant
      (P<0.0001) even when adjusted for hours worked. Up to 93.3% of male
      ophthalmologists are married or in a stable relationship, compared with 75.6% of
      females (P=0.0003), and males are more likely to have children (P=0.0007). There
      was no significant difference in overall career satisfaction between male and
      female ophthalmologists; however, females expressed greater frustration with
      managing professional and family commitments, and unequal career advancement
      opportunities. CONCLUSION: Significant differences exist in practice profiles and
      personal circumstances between male and female ophthalmologists. Females appear
      to balance work and personal responsibilities by working fewer hours, and for
      lower income. Despite this, they are less likely to be in a stable relationship,
      or to have children. However, there is no difference between the two groups in
      overall career satisfaction.

PMID- 17539783
TI  - Outcomes of combined penetrating keratoplasty and cataract extraction compared
      with penetrating keratoplasty alone.
AB  - PURPOSE: To compare the rejection rates, graft failure rates, mean visual,
      keratometric and refractive outcomes of combined penetrating keratoplasty and
      cataract extraction with penetrating keratoplasty alone. METHODS: A retrospective
      study of all patients who had combined keratoplasty and cataract
      extraction/intraocular lens insertion (49 eyes; mean age 65.3 years; mean follow
      up 17 months) compared with all patients who had keratoplasty only (58 eyes; mean
      age 64.0 years; mean follow up 14 months). RESULTS: One hundred and seven eyes in
      99 patients had keratoplasty in the period and were included in the study. The
      most common indication for keratoplasty in patients who had triple procedures was
      Fuchs' endothelial dystrophy (24.5%). During the study seven (6.5%) grafts failed
      and four (3.7%) had allogenic rejection without failure during this period. There
      was no statistical difference between the graft survival rates of the two study
      groups. The mean postoperative logMAR visual acuity (VA) was 0.42 and
      postoperative VA of 6/12 or better was seen in 71% of patients. Mean
      postoperative corneal curvature was 44.6 dioptres (D), mean corneal astigmatism
      was -4.0 D and was >or=5 D in 38%. Mean double-angle Cartesian coordinates for
      corneal astigmatism were x-0.87 D and y-0.29 D. Mean best sphere of postoperative
      refractions was -0.61 D and mean absolute refractive error was 2.2 D. There was
      no statistically significant difference in VA, keratometric or refractive outcome
      measures between the two study groups. CONCLUSION: Over a short follow up,
      keratoplasty combined with cataract extraction/intraocular lens insertion showed
      a similar risk of graft failure or allogenic graft rejection when compared with
      keratoplasty alone and we recommend the triple procedure for quicker visual
      recovery and less operative procedures.

PMID- 17539784
TI  - Factors influencing poor visual outcome in patients treated with photodynamic
      therapy for choroidal neovascularization secondary to age-related macular
      degeneration.
AB  - BACKGROUND: This study evaluated patients with choroidal neovascular membranes
      secondary to age-related macular degeneration for factors that may predict the
      visual outcome after photodynamic therapy. METHODS: A retrospective review of 172
      eyes of 172 consecutive patients who received photodynamic therapy for
      predominantly classic with and without occult, minimally classic and occult
      choroidal neovascular membranes secondary to macular degeneration in private
      practice from June 2000 to September 2004 was undertaken. All eyes had a baseline
      vision of 6/12 to 6/60. Classification of lesion composition, retreatment and
      follow up adhered to published photodynamic therapy guidelines. The primary
      outcomes measured were effects of patient age, baseline visual acuity, lesion
      composition and lesion size on final visual acuity and loss of less than 15
      letters of logMAR at 12 months. RESULTS: All eyes were followed up for 12 months.
      Baseline mean logMAR visual acuity was logMAR 0.64. Using multivariate logistic
      regression, loss of logMAR vision at 12 months was independently associated with
      increasing age (P=0.004), better baseline vision (P=0.009) and increasing lesion
      size (P=0.035). However, there was no association with lesion composition
      (P=0.16). At 12 months the loss of 15 letters or less was found in 101 (59.7%;
      95% confidence interval: 51.0-66.2%) of all patients. CONCLUSIONS: This study
      found no statistically significant association between lesion composition defined
      on fluorescein angiography and loss of visual acuity compared with previous
      studies. Factors associated with an increased rate of loss of 15 letters were
      increasing age of the patient, increasing lesion size and better baseline logMAR
      vision.

PMID- 17539785
TI  - Comparison of the rebound tonometer with the Goldmann applanation tonometer in
      glaucoma patients.
AB  - PURPOSE: To determine the agreement between the measurement of intraocular
      pressure (IOP) by the rebound tonometer (RBT) and by the Goldmann applanation
      tonometer (GAT) and to find out the effect of central corneal thickness (CCT)
      values on IOP measurements in glaucoma patients. METHODS: IOP was measured with
      the RBT and GAT, respectively, in 61 eyes of 61 glaucoma patients. CCT was
      measured using an ultrasonic pachymeter after all IOP determinations had been
      made. The mean IOP measurement by the RBT was compared with the measurement by
      the GAT, by Student's t-test. Bland-Altman analysis was performed to assess the
      clinical agreement between the two methods. The effect of CCT on measured IOP was
      explored by linear regression analysis. RESULTS: The mean patient age was 56.7+/
      21.1 years (range: 30-80 years). There were 32 (52.46%) women and 29 (47.54%) men
      in the study group. The mean IOP readings were 18.70+/-4.76 mmHg using the RBT,
      and 18.27+/-3.49 mmHg using the GAT. The difference was not statistically
      significant (mean difference 0.43+/-2.55, P=0.2). A frequency distribution of the
      differences demonstrated that in more than 80% of cases the IOP readings differed
      by <2.3 mmHg between the RBT and GAT. There was a strong correlation between the
      RBT and GAT readings (r=0.852, P<0.0001). The IOP measurements with the two
      methods were correlated with CCT (r=0.40, P=0.02 for the RBT and r=0.48, P<0.0001
      for the GAT). The IOP increased 1.1 mmHg and 8 mmHg for every 100-microm increase
      in CCT for the GAT and RBT, respectively. CONCLUSION: The RBT slightly
      overestimated the IOP value by 0.43 mmHg on average when compared with the GAT.
      Nevertheless, the RBT readings appeared to be more affected by the various
      thicknesses of different corneas when compared with those obtained using the GAT.

PMID- 17539786
TI  - Non-penetrating glaucoma surgery augmented with mitomycin C or 5-fluorouracil in
      eyes at high risk of failure of filtration surgery: long-term results.
AB  - PURPOSE: To investigate the long-term efficacy and safety of non-penetrating
      glaucoma surgery (NPGS) augmented with mitomycin C (MMC) or 5-fluorouracil (5FU)
      in eyes at high risk of failure of glaucoma filtration surgery. METHODS:
      Prospective study of all eyes, undergoing NPGS with 0.04% MMC (1 to 2 min topical
      or 0.04 mL subconjunctival injection into the superior fornix) or 5FU (25 mg/mL
      topically for 5 min). Complete success was an intraocular pressure (IOP)<or=21
      mmHg on no medication and qualified success an IOP<or=21 mmHg with topical
      medication. An additional criterion for success was a >or=20% drop in IOP or a
      reduction of at least two medications. RESULTS: Twenty-three eyes of 22 patients
      with a mean follow up of 41.4 months were reviewed. Fifteen eyes had failed
      trabeculectomy and seven had uveitic glaucoma. Mean preoperative IOP reduced from
      25.8+/-7.8 to 15.4+/-4.9 mmHg at final visit, a mean change of 41%. Median number
      of preoperative medications decreased from 3 to 0 postoperatively. Cumulative
      probability of success was 100% at 2 years, 94% at 3 years and 85% at 4 years. No
      patient developed any long-term complications. Complete success was achieved in
      11 eyes and qualified success in 10 eyes. Two eyes failed and required further
      surgery. CONCLUSION: NPGS augmented with small-volume MMC/5FU provides good long
      term IOP control in eyes at high risk of failure with a lower incidence of
      complications compared with augmented trabeculectomy and eliminates the need for
      postoperative bleb or suture manipulation.

PMID- 17539787
TI  - Nanophthalmos in a Melanesian population.
AB  - PURPOSE: To characterize the ophthalmic features and causes of visual loss in a
      cohort of Melanesians living in New Caledonia with nanophthalmos. METHODS: In
      this observational study, axial length, visual acuity (VA), cycloplegic
      autorefraction were assessed and dilated fundus examination was performed. Visual
      impairment was defined as VA<6/12 in the better eye, hypermetropia as >+1.0
      dioptre (D), astigmatism as >or=1.0 D and anisometropia as >or=1.0 D difference
      between both eyes. Unilateral amblyopia was defined as at least a two-line
      difference in VA between both eyes and bilateral amblyopia as VA<6/12 in both
      eyes which was not adequately explained by refractive error and macular folds.
      RESULTS: Seventeen community-dwelling participants (aged 1.1-45.3 years) with
      short axial length (range from 16.1 to 21.6 mm) were identified. Of the 17
      subjects, 14 were found to have crowded optic discs, three with papillomacular
      folds, three with a papillomacular band and three with macular radial folds.
      Further, all subjects demonstrated bilateral hypermetropia (range from +1.3 D to
      +15.1 D). A high proportion of subjects had astigmatism (12) and anisometropia
      (nine) in at least one eye. Visual impairment was found in nine subjects: five
      bilateral and four unilateral. Causes of visual impairment included amblyopia
      (seven), ametropia (seven) and macular folds (two). Amblyopia was attributed to
      several factors, including hypermetropia, anisometropia, astigmatism and
      esotropia. CONCLUSIONS: In this sample of Melanesians with nanophthalmos, a
      spectrum of ophthalmic features that was consistent with intraocular crowding was
      found. Over half of the subjects were visually impaired, mostly due to amblyopia
      and ametropia. Further characterization of the underlying genetic cause of
      nanophthalmos in this cohort will be the focus of future studies.

PMID- 17539788
TI  - Aberration and contrast sensitivity comparison of aspherical and monofocal and
      multifocal intraocular lens eyes.
AB  - BACKGROUND: Higher-order aberrations and contrast sensitivity were evaluated in
      patients who underwent phacoemulsification cataract extraction followed by
      implantation of aspherical, monofocal or multifocal intraocular lens (IOL)
      replacements. METHODS: In this comparative trial, 124 patients with an average
      age of 66.8+/-5.2 years and their 124 eyes were randomly divided into three
      surgical implantation groups to receive one of three types of IOLs in replacement
      of cataract lenses. The patients of group 1 were given an aspherical IOL Z9001
      (AMO, Santa Ana, CA, USA) replacement, and group 2 was implanted a monofocal IOL
      SA60AT (Alcon, Fort Worth, TX, USA) and group 3 the multifocal IOL SA40N (AMO).
      Post-surgical best-corrected visual acuity, corneal aberrations, total ocular
      aberrations, pupil diameters, capsulorhexsis sizes and contrast sensitivity were
      measured and compared. RESULTS: There was no statistical difference for mean best
      corrected visual acuity, pupil diameter, curvilinear capsulorhexis size and
      corneal aberration among the three groups. For the spherical aberration, fourth
      order higher-order aberration and total ocular higher-order aberration, the SA40N
      group was higher than the SA60AT group and the SA60AT group was higher than the
      Z9001 group, and the differences between the three groups were statistically
      significant for these measurements. Contrast sensitivity was higher for the Z9001
      group than the SA60AT group and the SA60AT group was higher than the SA40N group,
      and the difference was statistically significant in all the spatial frequencies
      of 3, 6, 12 and 18. CONCLUSIONS: Although the multifocal IOL can provide near
      vision, it can increase higher-order aberration and negatively influence contrast
      sensitivity. However, the aspherical IOL can reduce aberration and improve
      contrast sensitivity as compared with the monofocal IOL.

PMID- 17539789
TI  - Manifestation of Coats' disease by age in Taiwan.
AB  - BACKGROUND: To compare the differences in clinical manifestation of Coats'
      disease between younger and older patients in the Far East. METHODS: Coats'
      disease cases diagnosed at one Taiwanese hospital from July 1986 to June 2004
      were retrospectively reviewed (n=30; 32 eyes). Patients were stratified into
      groups according to the initial diagnosis of Coats' disease at the age of <20
      years (Group Y) or >or=20 years (Group O). The clinical manifestations of Coats'
      disease in Group Y (19 eyes) and Group O (13 eyes) were compared. RESULTS: A
      higher proportion of female patients was noted in Group O (P=0.046). Diseases
      were generally limited geographically, with 14 eyes (73.7%) manifesting
      involvement greater than 6 clock hours in Group Y and four eyes (30.8%) in Group
      O. The involved area including retinal telangiectasia and exudates was smaller in
      Group O (P=0.016). Patients without posterior pole involvement were associated
      with better visual outcome (adjusted odds ratio, 6.5; 95% confidence interval,
      1.1-40.1, P=0.044). CONCLUSION: Coats' disease manifestation was different
      between different age groups. Treatment is important to prevent disease
      progression. Visual prognosis is associated with posterior pole involvement.

PMID- 17539790
TI  - Late-onset post-traumatic Phaeoacremonium parasiticum endophthalmitis.
AB  - This is the first documented case of Phaeoacremonium parasiticum endophthalmitis
      to the authors' knowledge. P. parasiticum has been described in the literature
      causing various skin, subcutaneous and joint infections and one case of infective
      endocarditis, but has never been documented as an ocular infectious agent. The
      most likely source of inoculation in this case was a penetrating injury caused by
      a stick 5 years prior to the presentation. An enucleation was avoided through
      treatment with intravitreal antibiotics and amphotericin and oral voriconazole,
      and the patient's vision stabilized at 6/18. Microbiological studies were delayed
      but confirmed the mould's sensitivity to amphotericin B and voriconazole.

PMID- 17539791
TI  - Bilateral spontaneous idiopathic extraocular muscle haematoma.
AB  - The authors present a case of bilateral sequential extraocular muscle haematoma,
      for which no apparent cause has been identified despite extensive investigation,
      and which resolved without persisting morbidity. As far as the authors are aware,
      this is the first bilateral case to be reported.

PMID- 17539792
TI  - Mozart and smallpox.
AB  - In 1767 at 11 years of age, composer Wolfgang Amadeus Mozart contracted smallpox,
      allegedly causing him temporary blindness. Although now eradicated, smallpox in
      those days had a high mortality rate, and the history of classical music would
      have been very different if Mozart had become permanently blind, or died, as a
      result of the disease.

PMID- 17539793
TI  - Primary angle closure glaucoma: a developing world perspective.
AB  - Primary angle closure glaucoma (PACG) is estimated to affect a significant
      proportion of the population worldwide. Of those affected, the majority reside in
      developing countries. In the developing world, more than 80% of the people
      afflicted with glaucoma are unaware that they have the disease, and visual
      impairment from PACG is more severe than from primary open-angle glaucoma.
      Considering the paucity of resources and competing opportunity costs, it is
      imperative that the developing world extrapolates current literature and exiting
      data sensibly, and develops cost-effective strategies for the detection and
      management of angle closure glaucoma. The number needed to treat (NNT) was used
      to extrapolate the trials for an individual patient. To extrapolate to the
      overall population (where applicable) the authors used the population
      attributable risk percentage (PAR%). For individual patient care, treatment of a
      primary angle closure suspect (PACS) has an NNT of 6 over 5 years to prevent one
      patient progressing to primary angle closure (PAC). The NNT for PAC to prevent
      PACG over 5 years is 5. The 'effective' PAR% for PACS is 56.4% and the
      'effective' PAR% for PAC is 65%. This suggests both PACS and PAC are important
      health burdens but because of the absence of a good screening test and the
      opportunity costs involved, population-based screening will probably be
      unfeasible in developing countries.

PMID- 17539794
TI  - Optical coherence tomography evidence of rapid progression from vitreomacular
      traction to full thickness macular hole.
AB  - The authors present a case of a patient with idiopathic vitreomacular traction
      who subsequently developed a full thickness macular hole 3 weeks following the
      onset of metamorphopsia. Vitreomacular traction is a well described phenomenon
      and has been known to resolve spontaneously and in this patient the conservative
      approach was adopted initially. However, she progressed rapidly to a full
      thickness macular hole and therefore, the authors recommend close monitoring of
      such patients with a view to early vitrectomy to prevent progressive morbidity.

PMID- 17539795
TI  - Corneal perforation and intraocular lens prolapse in Serratia marcescens
      endophthalmitis.
AB  - A 72-year-old lady was referred with bacterial endophthalmitis secondary to
      complicated left cataract extraction. The organism was identified as Serratia
      marcescens. Despite aggressive treatment the eye continued to deteriorate with
      corneal perforation and prolapse of the intraocular contents.

PMID- 17539796
TI  - Intravitreal voriconazole for the treatment of endogenous endophthalmitis caused
      by Scedosporium apiospermum.
AB  - Scedosporium apiospermum is an increasingly recognized cause of endogenous fungal
      endophthalmitis in immunocompromised patients. The authors describe two patients
      with endogenous S. apiospermum endophthalmitis treated with intravitreal and
      systemic voriconazole. Despite a prolonged course of systemic antifungal
      treatment, both patients subsequently required enucleation for intractable ocular
      pain due to secondary scleritis. Histological examination of the globes
      demonstrated the presence of fungal hyphae. Endogenous S. apiospermum
      endophthalmitis need to be considered in the differential diagnosis of
      necrotizing retinitis. Despite its efficacy in suppressing disseminated S.
      apiospermum infection, voriconazole may be ineffective in the treatment of
      endogenous S. apiospermum endophthalmitis especially if treatment is delayed.

PMID- 17539797
TI  - Late intraocular pressure rise following intravitreal triamcinolone injection.
AB  - Most ophthalmologists are aware of the risk of elevated intraocular pressure
      developing 1 or 2 months after an intravitreal injection of triamcinolone.
      However, the two cases reported here demonstrate that such a rise can occur
      significantly later than this. All patients who have had intravitreal steroid
      injection should therefore have prolonged intraocular pressure monitoring.

PMID- 17539798
TI  - Sight-threatening orbital emphysema treated with needle decompression.
AB  - Orbital emphysema is rare in the absence of trauma, and is unlikely to result in
      visual loss. The authors describe a patient with no prior trauma who presented
      with decreased vision and increased intraocular pressure due to severe orbital
      emphysema after a sneeze. Computed tomography revealed subcutaneous emphysema of
      the lid and extraconal air in the orbit. Emergency needle decompression resulted
      in improvement in vision and intraocular pressure.

PMID- 17539799
TI  - Binocular membranous cataract associated with binocular retinal detachment.
AB  - A 36-year-old man with a history of consanguineous marriage between his parents
      presented with bilateral membranous cataract that was complicated by bilateral
      rhegmatogenous retinal detachment (RRD). Biomicroscopy revealed an absence of the
      crystalline lens bilaterally, a single piece of integrated fibrotic membrane in
      the right eye, and a membrane with a central cleft at the level of the ciliary
      process in the left eye. A small amount of residual cortex was revealed in the
      peripheral part of the membranes bilaterally when the pupils were dilated.
      Funduscopic examination showed that the vitreous liquefied and retina detached
      bilaterally. The successful retinal reattachment by vitrectomy and the finding of
      a retinal tear proved that the RD was rhegmatogenous. This case investigates
      bilateral membranous cataract with bilateral RRD as a new syndrome, or whether
      RRD may be a new complication of membrane cataract.

PMID- 17539800
TI  - Latanoprost-related transient incontinence.
AB  - Latanoprost has increasingly become the first choice in topical anti-glaucoma
      therapy. Local adverse events like hypertrichosis and increased iris pigmentation
      are common whereas systemic adverse events have been rare and mild in intensity.
      The authors would like to report a case of transient urge incontinence after
      initiation of latanoprost therapy confirmed by challenge-rechallenge tests and
      speculate on the causal relationship.

PMID- 17539802
TI  - Cataract surgery practice and endophthalmitis prevention by Australian and New
      Zealand ophthalmologists--comment.

PMID- 17539803
TI  - Recycled donated spectacles: experiences of eye care personnel in the Pacific.

PMID- 17539804
TI  - An assessment of recycled spectacles donated to a developing country--comment.

PMID- 17539807
TI  - An eye health strategy for Timor-Leste: the result of INGDO-government
      partnership and a consultative process.

PMID- 17539808
TI  - Hold on, first check that target!

PMID- 17539809
TI  - Basic clinical training in ophthalmology: correct misfires quickly!

PMID- 17539811
TI  - Pterygium excision with conjunctival autograft: consultant versus trainee.

PMID- 17539813
TI  - Spur cells and acanthocytes in liver diseases.

PMID- 17539814
TI  - Possible inhibitory effect of oral zinc supplementation on hepatic fibrosis
      through downregulation of TIMP-1: A pilot study.
AB  - AIM: To investigate the effect of oral zinc supplementation (polaprezinc) for 24
      weeks (34 mg/day zinc) on liver fibrosis in patients with advanced chronic liver
      disease. METHODS: Various markers of liver fibrosis, and fibrogenic and
      fibrolytic enzyme activities were measured before and after zinc supplementation
      in 17 patients with early cirrhosis. RESULTS: Serum zinc levels were decreased in
      the patients as compared with healthy controls. No side-effect was noted in any
      of the patients who received zinc supplementation. Serum levels of zinc increased
      by up to 156% over baseline levels in the group of patients who took oral zinc
      for 24 weeks. In patients whose serum zinc levels increased, the serum levels of
      type IV collagen and the activity of tissue inhibitors of metalloproteinase-1
      (TIMP-1) were significantly reduced, but no such change was observed in the other
      groups of patients, and no other serum markers changed. CONCLUSION: These results
      suggest that oral zinc supplement therapy with polaprezinc is safe and may be a
      novel and useful strategy for antifibrosis therapy in patients with early liver
      cirrhosis.

PMID- 17539815
TI  - A prospective study of acute drug-induced liver injury in patients suffering from
      non-alcoholic fatty liver disease.
AB  - AIM: Liver damage due to facultative hepatotoxins is scarcely foreseeable. We
      evaluated the prevalence of acute drug-induced liver injury (DILI) in a specific
      setting, assessing eventual interactions with pre-existing hepatic illnesses.
      METHODS: The research was carried out in an Italian tertiary care hospital, by
      analyzing 248 patients with non-advanced liver disease, divided into two well
      matched groups: 174 patients (median age 53, 94 females) with hepatitis C virus
      related chronic hepatitis; and 74 (median age 55, 39 females) with non-alcoholic
      fatty liver disease (NAFLD). RESULTS: Six patients (2.4% of the whole population)
      belonging to the NAFLD group (chi(2)-test, P = 0.004) suffered from acute
      hepatoxicity related to the following drugs, that is antihypertensive, acting on
      platelet aggregation, antimicrobial, non-steroidal anti-inflammatory and proton
      pump inhibitor. The NAFLD presence was an independent risk factor in determining
      drug-related acute hepatitis, with an odds ratio of 3.95 (95% confidence
      intervals: 11.48-1.35). Central obesity was relevant in every patient with acute
      toxicity. Alcohol consumption and drug association did not influence the acute
      drug-induced liver damage. CONCLUSION: NAFLD conveys a nearly fourfold increase
      of DILI risk in obese middle-aged patients. NAFLD, characterized by mitochondrial
      dysfunction, could predispose to drug-induced hepatotoxicity that probably shares
      the same pathophysiological mechanism.

PMID- 17539816
TI  - Hepatoprotective action of prostaglandin A(2) analogs under CCl(4)-induced liver
      injury in vitro.
AB  - AIM: The cytoprotective effects of six novel synthetic prostaglandin A(2) analogs
      against carbon tetrachloride (CCl(4)) as a toxic agent were studied with isolated
      rat liver hepatocytes in vitro. RESULTS: It was found that hepatocytes treatment
      with CCl(4) induced: (i) a significant increase of lactic dehydrogenase (LDH)
      release from cytoplasm; (ii) leakage of glutamate dehydrogenase (GDH) and acid
      phosphatase from mitochondria and lysosomes, respectively; (iii) 10-fold increase
      of trien conjugates formation; and (iv) a reduction of free SH-groups by 50%.
      Prostanoids U-26, U-9 and U-34 decreased cytotoxic index of CCl(4) on average by
      1.5-2.0 times and were more effective than PGI(2), the well-known hepatoprotector
      of prostanoids type. The protective action of the prostanoids was not a cAMP- or
      Ca(2+)-dependent process. However, prostanoids U-26, U-9 and U-34 normalized
      intracellular content of SH-groups, reduced trien conjugates formation by 60-80%
      and strongly prevented enzyme leakage through cellular membranes. They were also
      able to inhibit CCl(4) effects via decreasing cytochrome P(450)2E1 activity.
      CONCLUSION: The results obtained demonstrate that prostanoids provide
      cytoprotective effects on liver hepatocytes through the prevention of lipid
      peroxidation of the plasma and the cellular membranes and maintenance of their
      barrier function.

PMID- 17539817
TI  - Fusion protein containing SH3 domain of c-Abl induces hepatocarcinoma cells to
      apoptosis.
AB  - AIM: Through a preliminary test on a novel protein containing an HIV1-TAT domain
      and a SH3 domain of oncoprotein P210(BCR-ABL) (we named it after PTD-BCR/ABL
      SH3), we found that this protein shows inhibition activity of hepatocarcinoma
      cell HepG-2. The purpose of the present study is to explore the biological
      behavior of PTD-BCR/ABL SH3 fusion protein in hepatocarcinoma cells in vitro and
      in vivo. METHODS: HepG-2 cells were cocultured with the fusion protein for the
      indicated time and studied in vitro by immunocytochemistry staining to
      demonstrate the localization of the protein, light and electron microscope
      observation in morphology research, MTT assay to draw a growth curve and to
      analyze inhibition ratio, DNA ladder and TUNEL staining to study apoptosis. Nude
      mice bearing HepG-2 tumors were used to test the antitumor activity of the fusion
      protein. RESULTS: PTD-BCR/ABL SH3 fusion protein successfully entered into HepG-2
      cells and localized in the nucleus. The protein had shown high cytotoxity through
      inducing HepG-2 cells to apoptosis, and in vivo. The growth speed of tumors in
      the treatment group was distinctly slower than those in the control group, and
      the survival time of mice in the treatment group was longer than those in the
      control group. The growth of the tumors had been inhibited in the treatment
      group, while other tissues, such as heart, liver, lung and kidney displayed
      normal morphology. CONCLUSION: PTD-BCR/ABL SH3 fusion protein displays
      significant inhibitory activity of inducing hepatocarcinoma HepG-2 cells to
      apoptosis in vitro. It also showed therapeutic effects in vivo.

PMID- 17539818
TI  - Parametric imaging of contrast ultrasound for the evaluation of
      neovascularization in liver tumors.
AB  - AIM: To assess the efficacy of parametric imaging for the diagnosis of
      neovascularization in liver tumors. METHODS: The subjects were 17 rabbits (five
      with normal liver and 12 with VX2 tumor implanted in the liver). The contrast
      agents used were SonoVue (Bracco, Milan, Italy). A diagnostic ultrasound system
      was used with a programmable replenishment sequence. The images obtained between
      the initial frame after the high mechanical index (MI) scan, which diminishes
      microbubbles in the scan volume, and the current frame were coded in color
      according to the arrival and peak times. After the experiment, the tumors were
      excised and sectioned. Sections were prepared for light microscopy with
      hematoxylin-eosin (HE) staining and CD31 staining to evaluate vascular density.
      RESULTS: Arrival time imaging (ATI) delineated the fine blood vessels (100-200
      mum in diameter) in all of the rabbits. Tortuous and meandering tumor vessels
      were visualized in the VX2 tumors. Differences of perfusion velocity between
      tumor tissue and tumor-free areas were shown in peak time imaging (PTI).
      Vascularity evaluated on the ATI and perfusion speed recognized on the ATI and
      PTI were related to the vascular density measured by pathological investigation.
      CONCLUSION: Parametric imaging is a promising new method for the visualization of
      perfusion and the estimation of tumor blood vessels.

PMID- 17539819
TI  - Early upsurge in anti-HBs titer possibly caused by the immunomodulative, not by
      the mutagenetic effect of interferon and ribavirin.
AB  - A patient with chronic hepatitis B and C undergoing treatment with interferon and
      ribavirin showed an upsurge in hepatitis B virus surface antibody (anti-HBs)
      titer, accompanied by a decrease in hepatitis B virus surface antigen (HBsAg)
      during the early treatment phase. Simultaneously, elevation of alanine
      aminotransferase (ALT) was observed. Subsequently, the hepatitis B virus (HBV)
      DNA titer decreased and HBV e antigen (HBeAg) to anti-HBe seroconversion
      occurred. The anti-HBs titer gradually returned to the pretreatment level after
      cessation of ribavirin treatment and HBV-DNA became undetectable. We found no
      nucleotide mutations in HBV-DNA that could explain the sudden elevation in anti
      HBs titer. The appearance of anti-HBs was considered to be a break in immune
      tolerance against some epitopes in HBsAg, possibly the r epitope, stimulated by
      interferon/ribavirin treatment. The immunomodulatory effect of ribavirin might
      have caused this unexpected early immune response to HBsAg that preceded
      seroconversion to anti-HBe.

PMID- 17539820
TI  - Spur cell anemia associated with a cirrhotic non-alcoholic steatohepatitis
      patient.
AB  - Spur cell anemia is an acquired hemolytic anemia, which may occur in patients
      with severe liver dysfunction, especially in those with alcoholic cirrhosis.
      Recently, non-alcoholic steatohepatitis (NASH) has been highlighted as one of the
      causes of chronic liver diseases, which could progress to cirrhosis. Histological
      features of NASH are indistinguishable from those of alcoholic hepatitis. We
      report on a cirrhotic NASH patient who developed progressive indirect dominant
      jaundice and intractable hemolytic anemia during his follow-up. This report shows
      the first case of a cirrhotic NASH patient who died as a result of spur cell
      anemia.

PMID- 17539821
TI  - Conformational transition in the aminoacyl t-RNA site of the bacterial ribosome
      both in the presence and absence of an aminoglycoside antibiotic.
AB  - Peptide bonds are made at the ribosomal decoding site. Structural information
      reveals that two bases in the RNA that constitute the decoding site, A1492 and
      A1493, can have both intrahelical and extrahelical conformations. Aminoglycoside
      antibiotics bind to the decoding site, and the structural information reveals the
      two bases in the extrahelical positions. We have shown by explicit-solvent
      molecular dynamics simulations and free-energy calculations that ribosomal RNA
      bases A1492 and A1493 are inherently prone to sampling conformational states that
      include both intrahelical and extrahelical positions. The simulations reveal that
      base flipping occurs through the minor groove of the double helix. Furthermore,
      free-energy calculations for the conformational change of the bases to the
      extrahelical positions in both processes are exergonic and highly favorable. It
      is likely that the correct codon-anticodon recognition by mRNA and tRNA arrests
      the bases in extrahelical conformations in the course of normal translation. In
      contrast, the sequestration of the aminoglycoside antibiotic at the decoding site
      facilitates the conformational change of the bases to the extrahelical position.
      Once the antibiotic is bound, the extrahelical positions for the bases are highly
      favored based on contributions by both electrostatic and entropic components of
      the free energy for the process.

PMID- 17539822
TI  - Design of mutation-resistant HIV protease inhibitors with the substrate envelope
      hypothesis.
AB  - There is a clinical need for HIV protease inhibitors that can evade resistance
      mutations. One possible approach to designing such inhibitors relies upon the
      crystallographic observation that the substrates of HIV protease occupy a rather
      constant region within the binding site. In particular, it has been hypothesized
      that inhibitors which lie within this region will tend to resist clinically
      relevant mutations. The present study offers the first prospective evaluation of
      this hypothesis, via computational design of inhibitors predicted to conform to
      the substrate envelope, followed by synthesis and evaluation against wild-type
      and mutant proteases, as well as structural studies of complexes of the designed
      inhibitors with HIV protease. The results support the utility of the substrate
      envelope hypothesis as a guide to the design of robust protease inhibitors.

PMID- 17539823
TI  - Detection of sulfur mustard adducts in human callus by phage antibodies.
AB  - As part of a research program to develop novel methods for diagnosis of sulfur
      mustard exposure in the human skin the suitability of phage display was explored.
      Phage display is a relative new method that enables researchers to quickly
      evaluate a huge range of potentially useful antibodies, thereby bypassing the
      more costly and time-consuming hybridoma technique. The Tomlinson I and J phage
      libraries were used to select phage antibodies exhibiting affinity for sulfur
      mustard adducts on keratins, isolated from human callus. Two kinds of phage
      antibodies were obtained: antibodies recognizing keratin and antibodies
      recognizing keratin which was exposed to sulfur mustard. These phage antibodies
      retained activity after repeated culturing and culturing in larger volumes. For
      the first time antibody phage display was successfully applied for
      immunodiagnostics of a chemical warfare agent.

PMID- 17539824
TI  - Natural products active in aberrant c-Kit signaling.
AB  - Development of modulators of constitutively active, kinase domain mutants of c
      Kit has proved to be very difficult. Therefore, a high-throughput differential
      cytotoxicity assay was developed to screen for compounds that preferentially kill
      cells expressing constitutively active c-Kit. The cells used in the assay, murine
      IC2 mast cells, express either the D814Y activating mutation (functionally
      equivalent to human D816Y) or wild type protein. This assay is robust and highly
      reproducible. When applied to libraries of natural product extracts (followed by
      assay-guided fractionation), two differentially active compounds were identified.
      To assess possible mechanisms of action, the active compounds were tested for
      inhibitory activity against a panel of signaling enzymes (including wild type and
      mutant c-Kit). Neither of the compounds significantly affected any of the 73
      enzymes tested. The effects of commercially available modulators of known
      signaling components were also assessed using the screening assay. None of these
      inhibitors reproduced the differential activity seen with the natural products.
      Finally, both compounds were found to affect mitochondrial potential in cells
      expressing c-Kit(D814Y). These results suggest that the newly identified natural
      products may provide new avenues for intervention in aberrant c-Kit signaling
      pathways.

PMID- 17539825
TI  - 1H-1,2,4-triazol-3-yl-anilines: novel potent inhibitors of vascular endothelial
      growth factor receptors 1 and 2.
AB  - Novel derivatives of 1,2,4-triazoles are described as potent ATP-competitive
      inhibitors of vascular endothelial growth factor receptors I and II (VEGFR-1/2).
      A number of compounds display VEGFR-2 inhibitory activity comparable to that of
      Vatalanib and Vandetanib in both homogenous time-resolved fluorescence enzymatic
      and cellular assays. Several active molecules feature high intrinsic permeability
      (>30 x 10(-5) cm/min) across Caco-2 cell monolayer.

PMID- 17539826
TI  - Structure-activity relationships of melanocortin agonists containing the
      benzimidazole scaffold.
AB  - The melanocortin system has been implicated in regulating various physiological
      processes including pigmentation, energy homeostasis, obesity, steroidogenesis
      cardiovascular, and exocrine gland function. The five melanocortin receptors that
      belong to the super family of G protein-coupled receptors are stimulated by
      naturally occurring agonists. The aim of this research was focused on the design,
      synthesis, and pharmacological characterization of melanocortin ligands that
      contain the 1,2,5-trisubstituted benzimidazole scaffold. A series of
      benzimidazole analogues, with three points of diversity at positions 1, 2, and 5,
      were designed, synthesized, pharmacologically assayed at the mouse melanocortin
      receptors MC1R, MC3R, MC4R, and MC5R and resulted in ligands possessing a range
      of agonist activity from nm to no stimulation at up to 100 microM concentrations.
      This study demonstrates that the benzimidazole structure template can be appended
      with key melanocortin agonist amino acids for the design melanocortin receptor
      agonist ligands.

PMID- 17539827
TI  - Potent and selective peptide agonists of alpha-melanocyte stimulating hormone
      (alphaMSH) action at human melanocortin receptor 5; their synthesis and
      biological evaluation in vitro.
AB  - Melanocortin receptors (MC1-5R) and their endogenous ligands (melanocyte
      stimulating hormones and adrenocorticotropic hormone) are involved in many
      physiological processes in humans. Of those receptors, the actions of MC5R are
      the least understood despite its broad presence in the numerous peripheral
      tissues and brain. In this study, we describe synthesis and pharmacological
      properties in vitro (receptor-binding affinity and agonist activity) of several
      cyclic analogs of alphaMSH which are potent agonists at hMC5R (EC(50) below 1 nM)
      and of enhanced receptor subtype selectivity (more than 2000-fold versus hMC1b,3R
      and about 70- to 200-fold versus hMC4R). These compounds are analogs of Ac-Nle(4)
      cyclo[Asp(5)-His(6)-D-Nal(2')(7)-Pip(8)-Trp(9)-Lys(10)]-NH(2) (Pip: pipecolic
      acid) in which His(6) has been replaced with sterically hindered amino acids.
      They may be useful tools in the elucidation of the MC5R role in skin disorders
      and in immunomodulatory and in anti-inflammatory actions of alphaMSH.

PMID- 17539828
TI  - Development of aggregation inhibitors for amyloid-beta peptides and their
      evaluation by quartz-crystal microbalance.
AB  - A series of amyloid-beta aggregation inhibitors composed of a molecular
      recognition element (KLVFF) and an aggregation-disrupting part (having an
      electrostatic and hydrophilic nature) based on amino acid analogs have been
      synthesized. A quartz-crystal microbalance (QCM) method was applied and found to
      be very successful in evaluating the inhibitory activity of the Abeta
      aggregation, which was observed when the frequency was increased. The QCM can
      detect a mass change with differences in frequency that correspond to a 1 Hz
      frequency decrease per 30 pg mass increase on a 4.9 mm(2) electrode. Furthermore,
      bioassay results showed no toxicity of the inhibitor itself against IMR-32
      neuroblastoma cells, and remarkably reduced cytotoxicities of both Abeta1-40 and
      Abeta1-42 were exhibited in the presence of these inhibitors. The KLVFF-(EEX)3
      derivative was the most efficient Abeta aggregation among the inhibitors examined
      here.

PMID- 17539829
TI  - QSAR studies on the anesthetic action of some polyhalogenated ethers.
AB  - There has been an on-going debate about the mode of action of general anesthetics
      and until now, many sites have been postulated as target site for action of these
      compounds. Here, some quantum chemical-based quantitative structure-activity
      relationship (QSAR) models were developed for a set of polyhalogenated ethers in
      order to investigate the aspects of their anesthetic action, which is not
      completely defined yet, although some hypotheses have been suggested. A data set
      including 25 polyhalogenated methyl ethyl ethers were selected, and different
      descriptors were calculated for each molecule using density functional theory
      calculations, and subsequently some multilinear QSAR models were built by using
      different sets of the calculated molecular descriptors. The result showed that
      polar (polarizability) and non-polar (log P) parameters have mixed role on the
      anesthetic activity i.e. models with high statistical quality were obtained in
      combination with these two parameters. Also a good model between anesthetic
      action and electrostatic potentials was obtained, which may imply the important
      role of electronic interactions in the anesthetic activity of the compounds.
      Finally, a four-parametric QSAR model containing log P, molecular polarizability,
      most positive charge and an electrostatic potential parameters was obtained,
      which indicated that the anesthetic action of the polyhaloganted ethers may be
      proceeded through lipophilic, steric and columbic interactions.

PMID- 17539830
TI  - Inimitable elements of innovative drug discovery: quest for reverence and truth,
      and good works.

PMID- 17539832
TI  - It's time for an aetiology-based definition of chronic obstructive pulmonary
      disease.

PMID- 17539833
TI  - Non-small cell lung cancer: adjuvant and neo-adjuvant chemotherapy.
AB  - Of all cancers, non-small cell lung cancer is one of the most commonly diagnosed
      and is the deadliest. With a dismissal survival rate even in the early stages of
      disease, investigations of adjuvant and neo-adjuvant therapy have not had much
      impact until the 21st century. Starting in 2004, several randomized trials have
      shown significant improvements in survival treating patients with stage II and
      III disease. Adjuvant chemotherapy remains controversial in patients with stage I
      disease, in which most trials have not demonstrated a survival advantage.
      Investigators are studying molecular and genetic factors, which may predict who
      might benefit most from adjuvant therapy. While adjuvant therapy is now standard,
      neo-adjuvant therapy either with chemotherapy alone or with concurrent
      chemotherapy and radiation has shown promise, but has yet to become a clear
      standard of care. Data are presented to support the standard use of adjuvant
      therapy in patients with stage II and III disease, as well as data supporting the
      use of neo-adjuvant therapy in selected patients with non-small cell lung cancer.

PMID- 17539834
TI  - Lung cancer: new surgical approaches.
AB  - Over the past two decades, many surgical specialties have seen a dramatic shift
      from large, open operations with wide incisions towards more-minimal incisions
      and less-invasive procedures. Surgical techniques for lung cancer are no
      exception, and today, video-assisted thoracic surgical lobectomies are being
      performed with increasing frequency in large-volume thoracic practices. Despite
      these new surgical techniques, however, the most substantial innovations that
      have changed surgical outcomes occurred away from the operative theatre. In lung
      cancer, in particular, the last 20 years have witnessed the clinical debut of
      more sophisticated, more elegant and more accurate imaging modalities for
      improved screening, diagnostic and staging, such as the spiral CT scan, PET scan,
      PET/CT and the endobronchial ultrasound machine. This technology has been
      complimented by more targeted chemotherapeutic regimens, novel methods of
      administering more accurate and more concentrated doses of radiation therapy, and
      innovative local excisional methods, such as the Cyberknife and radiofrequency
      ablation. The result has been that surgical excision, although remaining the most
      effective local therapeutic modality in early-stage lung cancer, is no longer the
      'lone ranger' treatment, but rather is part of a complex mosaic of multimodality
      therapy. As scientific advances continue to be translated into the clinic, this
      trend will inexorably continue with the advent of a molecular staging system
      using molecular markers and tumour profiling, which ultimately could enhance our
      ability to predict tumour chemosensitivity. In this brave new world, however,
      complete surgical resection of the lung cancer will continue to be critical.

PMID- 17539835
TI  - Evaluation of a new inflammatory molecule (triggering receptor expressed on
      myeloid cells-1) in the diagnosis of pleural effusion.
AB  - BACKGROUND AND OBJECTIVE: The triggering receptor expressed on myeloid cell-1
      (TREM-1) is a newly discovered molecule that is associated with the inflammatory
      response to microorganisms. We investigated the role of surface and soluble TREM
      1 in differentiating different disease entities in pleural effusion formation.
      METHODS: Sixty-seven patients with pleural effusion due to transudate (14),
      malignancy (15), tuberculous pleuritis (16), para-pneumonic effusion (10) and
      empyaema (12) were included in this study. Surface TREM-1 was measured by flow
      cytometry and was expressed as mean fluorescence intensity and soluble TREM-1 was
      measured by ELISA and expressed as pg/mL. Results are given as mean levels +/-
      SEM. RESULTS: Surface TREM-1 was measured in 24 patients and the levels were
      highest in para-pneumonic effusion (30.0 +/- 8.4) and lowest in malignant pleural
      effusion (5.2 +/- 1.1) and tuberculous pleuritis (5.2 +/- 2.4). Soluble TREM-1
      was highest in effusions of infectious aetiology (para-pneumonic effusion (979.4
      +/- 229.6) and empyaema (1712.6 +/- 299.5)) and lowest in non-infectious
      effusions (transudate (81.2 +/- 4.5 pg/mL) and malignancy (111.3 +/- 20.7). At a
      cut-off value of 114 pg/mL, soluble TREM-1 yielded a sensitivity of 87.5% and a
      specificity of 89.7% in differentiating non-infectious effusion from tuberculous
      pleuritis. At a cut-off value of 374 pg/mL, sTREM-1 yielded a sensitivity of
      93.8% and a specificity of 90.9 in differentiating tuberculous pleuritis from
      bacterial pleural effusion. CONCLUSION: Soluble and surface TREM-1 are valuable
      markers in establishing the aetiology of pleural effusions.

PMID- 17539836
TI  - Elevated alpha-defensin levels in plasma of patients with pulmonary sarcoidosis.
AB  - BACKGROUND AND OBJECTIVES: Pathogens such as mycobacteria and proprionibacterium
      have been implicated in the pathogenesis of sarcoidosis. alpha-Defensins (DF) are
      naturally occurring antimicrobial peptides. The aim of the present study was to
      assess whether DF are increased in the airway and/or systemic circulation in
      patients with pulmonary sarcoidosis and whether DF levels are related to
      sarcoidosis disease activity. METHODS: DF levels in plasma and BAL fluid (BALF)
      were measured in 30 patients with pulmonary sarcoidosis and in 10 controls.
      Plasma and BALF DF levels were compared according to disease activity. Molecular
      forms were analysed using reverse-phase (RP) HPLC to confirm plasma and BALF DF
      kinetics in pulmonary sarcoidosis. RESULTS: DF concentrations in plasma and BALF
      were higher in patients with pulmonary sarcoidosis than in the controls. Plasma
      DF levels correlated with lysozyme but not with angiotensin-converting enzyme.
      These levels were high in patients in whom more organs were involved, whereas
      BALF DF levels were higher in patients at stage II or III than with those at
      sarcoidosis I. RP-HPLC showed high plasma levels of pro-defensins, DF precursors
      from the bone marrow, in sarcoidosis, although DF in peripheral neutrophils and
      BALF were the mature type. CONCLUSIONS: High plasma DF concentrations resulted
      from bone marrow stimulation and seemed to be associated with disease activity,
      whereas BALF DF were released from accumulated neutrophils in the lungs and may
      contribute to parenchymal involvement in sarcoidosis.

PMID- 17539837
TI  - Mycobacterial heat shock protein-induced blood T lymphocytes subsets and cytokine
      pattern: comparison of sarcoidosis with tuberculosis and healthy controls.
AB  - BACKGROUND AND OBJECTIVE: Sarcoidosis (SA) is a disorder of unknown aetiology.
      Mycobacterium tuberculosis heat shock proteins (Mtb-hsp) have been considered as
      causative agents of SA. The role of Mtb-hsp in the immune response in SA has not
      been investigated. METHODS: Mtb-hsp-stimulated T-cell subsets and Th1/Th2
      cytokine patterns in the supernatant from peripheral blood mononuclear cell
      cultures from 22 SA patients, 20 tuberculosis (TB) patients and 20 healthy
      volunteers were compared using flow cytometry. RESULTS: In unstimulated cultures,
      a significantly higher percentage of CD8(+)alphabeta(+)T-cells were present in SA
      versus controls. Similarly there was a significantly increased IL-6 and decreased
      IL-4 level in SA and significantly lower INF-gamma, IL-2, IL-4, IL-10 production
      in TB versus controls. After Mtb-hsp stimulation, there was a significantly
      increased TNF-alpha, IL-6, IL-10 and decreased INF-gamma, IL-2, IL-4 production
      in SA and significantly increased TNF-alpha, IL-6 concentrations in TB versus
      controls. CD8(+)gammadelta(+)IL-4(+)T-cells were detected significantly less
      often in Mtb-hsp-induced cultures in SA versus controls. Comparing SA versus TB,
      CD4(+)gammadelta(+)TCR-cells were significantly increased in Mtb-hsp-induced
      cultures in TB versus controls and SA. Before stimulation, significantly
      increased IL-6, IL-10 and decreased IL-4 level in SA versus TB was revealed,
      whereas Mtb-hsp stimulation caused significantly increased IL-10 and decreased IL
      4 concentrations in SA. CONCLUSIONS: After Mtb-hsp stimulation, increased levels
      of pro-inflammatory cytokines, TNF-alpha and IL-6 were found in sera from SA and
      TB patients in comparison with healthy controls; SA patients demonstrated the
      lowest levels of IL-4 and the highest levels of IL-10.

PMID- 17539838
TI  - Sarcoidosis in Singapore: epidemiology, clinical presentation and ethnic
      differences.
AB  - BACKGROUND AND OBJECTIVES: The aim of this study is to better understand the
      epidemiological and clinical features of patients with sarcoidosis in Singapore
      and to ascertain if ethnic differences exist. METHODS: A review of hospital
      medical records from June 1998 to May 2004 to identify patients with sarcoidosis.
      RESULTS: There were 59 patients with sarcoidosis identified (19 Chinese, 29 Asian
      Indian and 11 Malay). The estimated annual incidence of sarcoidosis in Singapore
      was 0.56 per 100,000. There was a significant difference between the observed and
      expected disease frequency in Chinese (32.2% vs 78.7%) and Indians (49.2% vs
      6.0%, P < 0.005). A bimodal distribution of age at diagnosis was seen with peaks
      in the 30-39 years and 50-59 years age groups; 38.9% of cases were over the age
      of 50. Chinese patients were more likely to be asymptomatic (57.9%, P = 0.015)
      and less likely to have impaired spirometry (P = 0.013). Pulmonary sarcoid
      presented largely as stage 0 or stage 1 disease (74.4%). Overall mean spirometry
      was unimpaired and prognosis was good with 79.2% showing no radiological
      deterioration. There were no significant differences in organ involvement or
      treatment between ethnic groups. CONCLUSION: Sarcoidosis in Singapore is rare and
      the incidence differs between ethnic groups. Chinese appear to have a lower
      incidence and a less symptomatic presentation; Indians have a higher incidence
      and poorer clinical course.

PMID- 17539839
TI  - Arm span as an independent predictor of pulmonary function parameters: validation
      and reference values.
AB  - BACKGROUND AND OBJECTIVES: To determine if arm span can be used as a measure of
      body length in developing prediction equations for lung function and to compare
      these equations with height-derived equations. METHODS: Standing height and arm
      span were measured for all study subjects. Spirometry measurements included FVC,
      FEV(1), FEV(1)/FVC ratio, PEFR, FEF(25), FEF(50), FEF(75) and FEF(25-75). These
      data were used to develop prediction equations using multiple regression analysis
      based on age, gender and arm span. An independent group (225 subjects) was used
      to evaluate the accuracy of the equations. Predicted values for each parameter
      were calculated separately for arm span and height and compared with the measured
      values. RESULTS: Study subjects comprised 1865 healthy non-smoking Persian
      volunteers. Arm span-based equations accurately predicted all of the spirometric
      parameters. The standard errors of the estimate for prediction equations based on
      arm span were slightly smaller than those based on standing height. Average
      predicted values based on height predicted from arm span did not consistently
      agree with the measured values. CONCLUSIONS: Predicting pulmonary parameters
      using equations based on arm span is as reliable as using equations based on
      standing height and are more accurate for patients in whom height cannot be
      measured reliably.

PMID- 17539840
TI  - Pulmonary function testing in New Zealand: the use and importance of reference
      ranges.
AB  - BACKGROUND AND OBJECTIVES: The diagnosis, assessment and management of a wide
      range of respiratory diseases rely on accurate interpretation of lung function
      tests through the use of reference equations to generate predicted values. This
      paper ascertains the suitability of reference equations currently used in New
      Zealand through comparison with newly derived equations from the Wellington
      Respiratory Survey, and discusses the relevance of the findings to the Asia
      Pacific region. METHODS: A survey of lung function testing facilities determined
      the reference equations in common usage. Pulmonary function test results from
      healthy, lifelong non-smoking subjects (n = 180) were expressed as percentage
      predicted values, with comparisons made between the currently used and Wellington
      Respiratory Survey reference equations. Differences in disease severity
      classification in subjects with COPD (n = 46) and asthma (n = 61) were
      determined, using the different reference equations. RESULTS: Currently used
      equations significantly underpredict measured values for FEV(1), PEF, TLC and RV
      by up to 20%. Severity classification of COPD and asthma based on per cent
      predicted FEV(1) was substantially altered by the choice of reference equation.
      CONCLUSION: Many reference equations in current usage in New Zealand are no
      longer suitable for use. The applicability of reference equations used in other
      populations and countries within the Asia Pacific region requires further
      investigation. We recommend that up-to-date reference equations are derived and
      implemented if those currently used are shown to be unsatisfactory.

PMID- 17539841
TI  - Snoring and breathing pauses during sleep in the Malaysian population.
AB  - OBJECTIVE: The aim of this study was to determine the prevalence of snoring and
      breathing pauses during sleep, and to assess associated factors, including
      morbidity and the impact on daytime functioning, in an adult Malaysian
      population. METHODS: A cross-sectional survey of community-dwelling adults aged
      30-70 years was conducted. Daytime sleepiness was assessed using the Epworth
      Sleepiness Scale. Physical examinations were limited to measurements of body
      habitus and blood pressure. RESULTS: The sample consisted of 1611 adults (52.9%
      male). The prevalence of habitual snoring, breathing pauses and excessive daytime
      sleepiness were 47.3%, 15.2% and 14.8%, respectively. Seven per cent of
      respondents (8.8% male, 5.1% female) were clinically suspected to have
      obstructive sleep apnoea syndrome (OSAS). The independent predictors of habitual
      snoring were older age, Chinese or Indian ethnicity (compared with Malays),
      smoking, obesity and use of sedatives. Clinically suspected OSAS and habitual
      snoring were significantly associated with difficulty in getting up in the
      morning, morning headache, driving and workplace accidents, hypertension, and
      ischaemic heart disease. CONCLUSIONS: The prevalence of habitual snoring is high
      in the Malaysian population. Sleep-related breathing disorders in Malaysian
      adults are associated with significant morbidity.

PMID- 17539842
TI  - Effects of high-intensity exercise training in a pulmonary rehabilitation
      programme for patients with chronic obstructive pulmonary disease.
AB  - BACKGROUND AND OBJECTIVES: The benefits of pulmonary rehabilitation for patients
      with COPD depend on the intensity of training. Traditional pulmonary
      rehabilitation programmes (PRPs) do not consistently achieve high-intensity
      training and have variable training effects. This study examined the effects of
      high-intensity exercise training on cardiac and pulmonary function in COPD
      patients. METHODS: Patients with COPD participated in a 6-week, cardiopulmonary
      exercise test-based PRP. Spirometry, 6-min walking distance and cardiopulmonary
      exercise test were used to evaluate cardiopulmonary function, respiratory muscle
      strength and endurance at rest, during exercise and before and after the
      programme. Patients were encouraged to complete high-intensity exercise with a
      targeted training intensity of at least 75% maximum oxygen uptake (VO(2)).
      RESULTS: Thirty-four COPD patients were enrolled into the study; 16 completed the
      high-intensity training, 18 did not. At the end of the 12-session PRP, submaximal
      exercise capacity (6-min walking distance, 461.8 +/- 77.2-502.7 +/- 66.9 m, P <
      0.001) improved in both the patients who completed high-intensity training and
      those who did not. Only the patients who completed high-intensity training had
      significant improvements in FVC (2.47 +/- 0.70-2.70 +/- 0.62 L, P = 0.024) at
      rest, maximal exercise capacity (peak VO(2), 1001.6 +/- 286.4-1116.1 +/- 320.4
      mL/min, P = 0.020) and work efficiency (7.3 +/- 1.4-8.4 +/- 1.8 mL/min/watt, P =
      0.026). There was no statistically significant difference between the two groups
      in the change in the physiological parameters before and after exercise.
      CONCLUSIONS: Exercise training in a PRP improved submaximal exercise capacity.
      Only patients who completed high-intensity exercise training showed improvements
      in maximal exercise capacity, FVC and work efficiency.

PMID- 17539843
TI  - Effect of a simple educational intervention on the hospital management of
      community-acquired pneumonia.
AB  - BACKGROUND AND OBJECTIVES: Both the speed of commencement and the appropriateness
      of i.v. antibiotic administration influence outcomes in patients hospitalized
      with community-acquired pneumonia (CAP). While quality improvement projects have
      been linked to better CAP management and outcomes, there are limited data
      evaluating simple and achievable interventions. METHODS: A simple educational
      programme targeting rapid and appropriate antibiotic administration for the
      inpatient treatment of CAP was evaluated using a retrospective chart review of
      all patients admitted through the emergency department with CAP during 'pre
      intervention' and 'post-intervention' periods. RESULTS: There were 108 pre
      intervention patients (56 women, median age 63 years) and 88 post-intervention
      patients (43 women, median age 61 years) included in the evaluation. Comparison
      of indicators of care in the post-intervention period with those in the pre
      intervention period showed there were significant changes in: median time to
      antibiotic administration (2.5 h vs 3.5 h, 95% CI: 0-1.25, P = 0.01); subjects
      not prescribed macrolide antibiotics (2.3% vs 10.2%, 95% CI for OR 1.02-46.19, P
      = 0.04); hospital length of stay (3.5 vs 6 days, 95% CI: 1-3, P < 0.001) and
      mortality (0% vs 6.5%, 95% CI for OR 1.13 to infinity, P = 0.02). CONCLUSION: A
      simple, inexpensive educational intervention was associated with significant
      improvements in the hospital management of CAP. The widespread introduction of
      similar programmes has the potential to effect substantial improvements in
      management, and possibly patient outcomes, and requires prospective confirmation
      in a larger, randomized sample.

PMID- 17539844
TI  - Pulmonary nocardiosis: risk factors and outcomes.
AB  - BACKGROUND AND OBJECTIVES: Pulmonary nocardiosis (PN) is an infrequent but severe
      infection caused by Nocardia spp., which can behave either as opportunistic or
      primary pathogens. The present study identifies the risk factors for PN, clinical
      symptoms and radiographic features and the factors that affect its prognosis.
      METHODS: An observational study of all the patients diagnosed with PN over a 13
      year period at the authors' institution. RESULTS: Thirty-one adult patients were
      identified with PN, 11 of whom had disseminated nocardiosis. The predisposing
      conditions were COPD (23%), transplantation (29%), HIV infection (19%),
      alcoholism (6.5%) and treatment with steroids (64.5%). Respiratory tract sampling
      using non-invasive techniques had a diagnostic yield of 77%, while specimens from
      invasive methods had a yield of 47%. Mean time to diagnosis was 42 days.
      Dissemination to the central nervous system was related to alcoholism. The
      mortality rates were 41% for PN and 64% for disseminated nocardiosis; when
      Nocardia disseminated to the central nervous system, the mortality was 100%.
      CONCLUSION: Specific risk factors were found in 94% of patients, with the most
      common being corticosteroid treatment and immunosuppressive therapy. The time to
      reach diagnosis and to prescribe specific treatment was considerable and
      mandatory assessment for nocardia in high-risk patients is required. The
      mortality rate of PN is high and early diagnosis and treatment are needed.
      Medications other than co-trimoxazole may be required.

PMID- 17539845
TI  - Clinical characteristics of tuberculosis in patients with liver cirrhosis.
AB  - BACKGROUND AND OBJECTIVES: Patients with liver cirrhosis are likely to be
      susceptible to tuberculosis (TB) because of immune system dysfunction. The aim of
      this study was to elucidate the clinical characteristics and treatment responses
      in TB patients with cirrhosis. METHODS: Cases were patients with TB detected
      during their follow up for liver cirrhosis over a 4-year period. Controls were
      randomly selected patients with TB but no liver disease, matched to cases by age
      and gender in a 3:1 ratio. RESULTS: Thirty-six cases and 108 controls were
      enrolled. Extrapulmonary TB was more common in cases than controls (31% vs 12%, P
      = 0.02). Clinical and radiographic manifestations and response to treatment did
      not differ between the two groups. The frequency of hepatotoxicity was higher in
      the cases than in the controls who were treated with a regimen containing
      rifampicin and isoniazid, although the difference was not statistically
      significant (27% vs 10%, P = 0.079). CONCLUSIONS: TB patients with liver
      cirrhosis show extrapulmonary involvement more frequently. Patients with
      pulmonary TB and cirrhosis usually respond well to anti-TB treatment although
      appear to present more frequently with treatment-related hepatotoxicity.

PMID- 17539846
TI  - Prognostic factors in pulmonary tuberculosis requiring mechanical ventilation for
      acute respiratory failure.
AB  - BACKGROUND AND OBJECTIVE: The prognosis in patients with pulmonary tuberculosis
      and acute respiratory failure requiring mechanical ventilation is believed to be
      poor. The aim of this study was to identify factors contributing to in-hospital
      mortality in these patients. METHODS: The medical records of 32 patients with
      active pulmonary tuberculosis as a primary cause of acute respiratory failure
      requiring mechanical ventilation in the medical intensive care unit (ICU) of a
      tertiary referral hospital over a 10-year period were reviewed retrospectively,
      and predictors of mortality were assessed. RESULTS: The patients' median age was
      69 years (range 25-88 years). The median length of intensive care unit stay was
      11 days (range 2-88 days), and the median duration of mechanical ventilation was
      9 days (range 2-86 days). Overall in-hospital mortality was 59% (19/32).
      Independent predictive factors of in-hospital mortality included tuberculous
      destroyed lungs (hazard ratio 6.61, 95% CI: 1.21-36.04, P = 0.029), Acute
      Physiology and Chronic Health Evaluation II scores > or =20 (hazard ratio 4.90,
      95% CI: 1.43-16.80, P = 0.012) and sepsis (hazard ratio 5.84, 95% CI: 1.63-20.95,
      P = 0.007). CONCLUSION: Acute respiratory failure caused by pulmonary
      tuberculosis necessitating mechanical ventilation has a high mortality rate and
      poor prognosis, particularly in patients with tuberculous-destroyed lungs, high
      Acute Physiology and Chronic Health Evaluation II scores and sepsis.

PMID- 17539847
TI  - Routine culture for Mycobacterium tuberculosis from bronchoscopy in Taiwan.
AB  - BACKGROUND AND OBJECTIVE: The value of routine culture for mycobacterium from
      bronchoscopic washings and the cost-effectiveness is still uncertain in countries
      where tuberculosis is endemic. This study examined the epidemiology of positive
      cultures for M. tuberculosis obtained by bronchoscopy to determine the health
      benefit and cost of a policy of routine culture and smear. METHODS: All positive
      cultures for Mycobacterium tuberculosis in bronchial washings and the
      corresponding CXR features were analysed. RESULTS: The incidence of tuberculosis
      in routine bronchoscopy was 3.71%, and in patients who presented with typical
      tuberculosis features on CXR was 6.5%. Up to 10.6% of culture-proven pulmonary
      tuberculosis relied on bronchoscopy for diagnosis. The total cost of routine
      mycobacterium culture and acid-fast bacillus smear during the 2-year period was
      approximately US $24,800. CONCLUSION: Routine mycobacterium culture and acid-fast
      staining from bronchoscopic specimens appears to be valuable in countries where
      tuberculosis is prevalent.

PMID- 17539848
TI  - Pneumoconiosis and liver cirrhosis are not risk factors for tuberculosis in
      patients with pulmonary infection.
AB  - BACKGROUND AND OBJECTIVE: It is unclear whether patients with liver cirrhosis and
      coal miners with pneumoconiosis are at increased risk of developing pulmonary
      tuberculosis (TB). Furthermore, little is known of the likelihood of pneumonia in
      patients with bronchiectasis, haemodialysis, diabetes mellitus or advanced lung
      cancer being due to TB. To answer these questions, patients with these clinical
      comorbidities were analysed. METHODS: The study was retrospective and included
      264 TB patients, 478 non-TB pneumonia patients, and as negative controls, 438
      subjects without pneumonia. The parameters analysed were age, gender and the
      presence of pneumoconiosis, bronchiectasis, liver cirrhosis, haemodialysis,
      diabetes mellitus and advanced lung cancer. RESULTS: Male gender was the only
      significant factor increasing the risk of pulmonary TB. When compared with non-TB
      pneumonia and control patients, the odds ratios were 1.862 and 2.182,
      respectively. Patients with liver cirrhosis did not show an increased risk of
      pulmonary TB after regression analysis. Pneumoconiosis resulted in a 2.260 (P =
      0.003) odds ratio for pulmonary TB, compared with the controls. However, there
      was no difference in pneumoconiosis between TB and non-TB pneumonia patients.
      Patients with bronchiectasis, lung cancer and those receiving haemodialysis had a
      lower risk for pulmonary TB in lower respiratory tract infection, with odds
      ratios of 0.342, 0.311 and 0.182, respectively. CONCLUSION: Physicians should
      first consider non-TB bacterial infection rather than Mycobacterium tuberculosis
      infection in pneumonia in patients with bronchiectasis, lung cancer or those
      receiving haemodialysis.

PMID- 17539849
TI  - Evaluation of the relationship between radiological abnormalities and both
      pulmonary function and pulmonary hypertension in coal workers' pneumoconiosis.
AB  - OBJECTIVE: The aim of this study was to investigate the effect of the
      radiological evidence of emphysema, and the extent of interstitial involvement,
      on lung function and pulmonary arterial pressure (PAP) in patients with coal
      workers' pneumoconiosis (CWP). METHODS: The records of 48 patients with suspected
      CWP were evaluated retrospectively. Pulmonary function tests, arterial blood gas
      analyses and right heart catheterization were evaluated in all patients.
      Radiological scoring was according to International Labour Organization criteria,
      and emphysema was scored by CT scanning. Patients were grouped according to the
      mean PAP (> or =20 mm Hg or < or =19 mm Hg). RESULTS: All patients showed a mild
      decrease in FEV(1)/FVC and a mild increase in FRC. Forty-four per cent of
      patients developed mild to moderate pulmonary hypertension. Emphysema scores
      correlated significantly with airflow rates, including FEV(1)%, FEV(1)/FVC and
      FEF(25-75%), and with carbon monoxide diffusing capacity (DLCO)% predicted as
      well as FRC% predicted and the ratio RV/TLC, which are indices of air trapping.
      Additionally, profusion and global profusion scores showed significant
      correlation with FEV(1)/FVC, DLCO% predicted, specific airway conductance and
      smoking. Mean PAP showed a significant negative correlation with FEF(50%)
      predicted, DLCO% predicted and profusion score. CONCLUSIONS: The impairment of
      pulmonary function (mainly disturbance in airflow rates and air trapping) and
      pulmonary hypertension may be present, even in a simple form of CWP. The
      pulmonary function impairment in patients with CWP is likely to be attributable
      to the occurrence of emphysema. However, pulmonary hypertension was directly
      related to the profusion of pneumoconiotic nodules, which may result in
      obliteration of the vascular bed.

PMID- 17539850
TI  - Gender-associated differences in dyspnoea and health-related quality of life in
      patients with chronic obstructive pulmonary disease.
AB  - BACKGROUND AND OBJECTIVES: Recent studies have reported several gender-associated
      differences among patients with COPD, but gender-associated differences in health
      related quality of life (HRQoL) in patients with COPD have not yet been
      clarified. This study evaluated gender differences in dyspnoea and HRQoL in
      patients with COPD. METHODS: Study participants were 156 patients with COPD (men
      117, women 39); men were individually matched to women by age and FEV(1)%
      predicted to give a ratio of 3:1 (male : female). Study participants were
      evaluated for dyspnoea and completed HRQoL questionnaires. An oxygen cost diagram
      (OCD) was used to assess the degree of dyspnoea and Morale Scale was used to
      assess subjective well-being. St. George's Respiratory Questionnaire (SGRQ) and
      SF-36 were used for HRQoL evaluation. The findings in the male and female groups
      were compared. RESULTS: The OCD and Morale Scale showed significantly lower
      values for female patients with COPD. Disease-specific HRQoL assessed by SGRQ was
      significantly worse, except for symptoms, in female patients with COPD. Generic
      HRQoL assessed by SF-36 was also significantly worse, except for general health
      and social functioning. Stepwise multiple regression showed OCD, Morale Scale and
      6-min walking distance to be significantly associated with total SGRQ score in
      the male group, and Morale Scale and 6-min walking distance were significant
      associations in the female group. CONCLUSIONS: Gender differences exist in
      dyspnoea and HRQoL in patients with COPD. These need to be considered when
      designing treatment strategies for COPD patients.

PMID- 17539851
TI  - Cost of hospitalizing asthma patients in a regional hospital in Thailand.
AB  - BACKGROUND AND OBJECTIVE: The hospitalization of asthma patients accounts for
      substantial costs in any health-care system. However, the utilization of medical
      resources and the cost of hospitalizing asthma patients in Thailand have never
      been evaluated. This study aimed to evaluate the utilization of health-care
      resources and itemize the cost of hospitalizing asthma patients in a regional
      hospital in north-east Thailand. METHODS: A cross-sectional, retrospective study
      was conducted at Surin Hospital, a 697-bed, regional hospital in north-east
      Thailand. The study included 183 adults (> or =15 years of age) who were admitted
      with acute asthma. Demographic data, resource-utilization parameters and itemized
      costs were recorded. RESULTS: The average hospital cost was 5,809.3 +/- 6,587.4
      Thai Baht (US $134.5 +/- 152.5) per patient (range, 740-57,980 Thai Baht or US
      $17.1-1,342.1). Medications were the primary hospital expense (47.2%), followed
      by hospital charges (13.5%), nursing care (13.0%) and respiratory therapy
      (12.2%). Fifteen per cent of patients accounted for 45% of total hospital costs.
      Significant predictors of increased total hospital cost were: (i) age > or =60
      years; (ii) presence of comorbid conditions; (iii) admission to the intensive
      care unit; and/or (iv) prolonged hospital stay. CONCLUSION: Despite the low unit
      costs for inpatient care in Thailand, the cost of hospitalizing asthma patients
      (especially the elderly) constitutes a substantial burden to the health-care
      system.

PMID- 17539852
TI  - Lipid peroxides in stable asthmatics receiving inhaled steroids and long-acting
      beta2 -agonists.
AB  - BACKGROUND AND OBJECTIVE: The effect of inhaled steroids on oxidative stress in
      asthmatics is unclear. The levels of lipid peroxides in the serum of asthmatic
      patients, whose symptoms were controlled with inhaled corticosteroids and long
      acting beta(2)-agonists, were measured in this study. METHODS: Twenty asthmatic
      patients and 17 matched, healthy controls were recruited. Oxidative stress levels
      were quantified by measuring thiobarbituric acid reactive substances. RESULTS:
      After 3 months of treatment, the mean lipid peroxide concentrations were
      significantly higher in asthmatic patients than in the healthy controls (4.2 +/-
      0.13 micromol/mL vs. 3.6 +/- 0.07 micromol/mL, respectively). CONCLUSION: The
      level of lipid peroxides is higher in patients with asthma than in healthy
      controls, even when the asthma is well controlled after 3 months of treatment. A
      longer period of therapy may be required before lipid peroxidation normalizes.

PMID- 17539853
TI  - Video-assisted thoracic surgery for spontaneous haemopneumothorax.
AB  - BACKGROUND AND OBJECTIVE: The aim of this study was to review the treatment
      options for spontaneous haemopneumothorax (SHP) by video-assisted thoracoscopic
      surgery (VATS). METHODS: Records from 16 patients (14 male, age 16-38 years, mean
      age 26.1 years) with prominent SHP (blood loss over 400 cc in the first 24 h)
      undergoing VATS from July 1994 to December 2005 and treated by one thoracic
      surgeon in four medical centres or community hospitals of North and Mid-Taiwan
      were reviewed retrospectively. RESULTS: Thirteen patients (81.3%) were identified
      to have a prominent bleeding source intraoperatively. Torn engorged vessels from
      the parietal pleura to adjacent bullae were found in nine patients, and bleeders
      adjacent or over the parietal part of the adhered pleura were found in the other
      four. Ruptured bullae/blebs or air leakage were found in 14 (87.5%). All
      underwent removal of intrapleural blood clot, control of bleeders and their
      bullae/blebs were resected through three-port VATS (n = 13, 81.2%) or mini
      thoracotomy and VATS (n = 3, because of unstable vital signs or conversion
      because of dense adhesion). Mechanical or chemical pleurodesis was carried out in
      all patients. The mean operative time was 53.8 +/- 21.7 min. There was no
      postoperative mortality. However, recurrent bleeding requiring reoperation
      occurred in one patient, and one other patient had a prolonged air leakage (>7
      days) postoperatively and recovered spontaneously. The mean duration of chest
      tube drainage was 3.8 days and the median follow-up period was 3.2 years.
      CONCLUSION: SHP complicated by severe bleeding is a surgical emergency. VATS is a
      reasonable treatment for patients with SHP.

PMID- 17539854
TI  - Recent discovery of an old disease: malignant pleural mesothelioma in a village
      in south-east Turkey.
AB  - BACKGROUND AND OBJECTIVE: Environmental asbestos exposure is reportedly common in
      some districts of Turkey. The aim of this study was to investigate the presence
      and effect of environmental asbestos exposure in a village in Gaziantep, Turkey,
      with reported cases of mesothelioma. METHODS: All villagers > or =14 years old
      were subject to an interview rediagnosis and a detailed questionnaire. Chest
      microfilms were performed in all cases, and additional standard CXRs were
      obtained when necessary. Samples collected from the natural mantle, and whitewash
      from the houses were analysed for the presence of asbestos. RESULTS: In total,
      269 villagers took part in the study. The incidence of histopathologically
      diagnosed malignant pleural mesothelioma was 0.32% relative to the total village
      population in the year 2000. The verbal autopsy revealed eight possible cases of
      malignant pleural mesothelioma, all of whom had died within the past 12 years. Of
      these eight, there was a first-degree kinship between three, and additionally,
      these patients had a third-degree relationship with a biopsy proven case.
      Radiological evaluation showed pleural calcification and/or thickness in 3.3%,
      and pleural effusion in 0.4% of patients undergoing CXR. All houses in the
      village were constructed using adobe soil, and the interior whitewash was made
      from soil containing asbestos. Analysis of soil samples revealed tremolite and/or
      actinolyte asbestos. CONCLUSION: The current findings suggest that environmental
      asbestos exposure continue to be a serious health concern in the Gaziantep region
      of Turkey.

PMID- 17539855
TI  - Peripheral T-cell lymphoma with diffuse pulmonary infiltration and an increase in
      serum KL-6 level.
AB  - Peripheral T-cell lymphoma is a subtype of non-Hodgkin's lymphoma. A case of
      peripheral T-cell lymphoma showing diffuse pulmonary involvement together with a
      marked increase in the level of serum KL-6 is presented. CXR and CT revealed
      reticular and ground-glass opacities, which mimicked interstitial pneumonia.
      Immunopathological findings and an analysis of T-cell receptor gene
      rearrangements of the lung biopsy specimen led to a definite diagnosis of
      peripheral T-cell lymphoma. In addition, the extensive proliferation of type II
      pneumocytes, which stained strongly positive for anti-KL-6 antibody suggested
      that the pneumocytes were the source of serum KL-6.

PMID- 17539856
TI  - Inflammatory lesions of the lung, submandibular gland, bile duct and prostate in
      a patient with IgG4-associated multifocal systemic fibrosclerosis.
AB  - Multifocal systemic fibrosclerosis (MSF) is a multisystem disease, which often
      mimics malignancy. A 70-year-old asymptomatic man with lesions in the lung,
      prostate, submandibular glands and bile ducts appeared to have malignancy. Biopsy
      of a lung nodule showed IgG4-positive plasma cell infiltration and the serum IgG4
      was elevated. A diagnosis of MSF was made and the patient treated with oral
      prednisolone at 1 mg/kg/day. Sclerosing cholangitis, retroperitoneal fibrosis,
      Riedel's thyroiditis, fibrotic pseudotumor of the orbit and fibrosis of the
      salivary glands have all been reported to be part of this disease. It is now
      necessary for MSF to be considered in patients with pulmonary lesions mimicking
      lung cancer.

PMID- 17539857
TI  - Radiological findings of alveolar hydatid disease of the lung caused by
      Echinococcus multilocularis.
AB  - Alveolar hydatid disease is a highly malignant form of echinococcosis caused by
      the larvae of the cestode Echinococcus multilocularis. Alveolar hydatid disease
      always affects the liver and can metastasise to the lungs and brain. The case
      reports describe the radiological features of alveolar hydatid disease of the
      lung caused by E. multilocularis. Multiple nodules which varied in size and shape
      were seen on CXR, CT showed most nodules to be lobulated, well circumscribed and
      of varying shape. Multiple lobulated lesions located between two segments of the
      lung and of varying shape appear to be characteristic of pulmonary alveolar
      hydatid disease caused by E. multilocularis.

PMID- 17539858
TI  - Hydatid cyst presenting as an eosinophilic pleural effusion.
AB  - A 61-year-old woman presented with an eosinophilic pleural effusion, secondary to
      transdiaphragmatic intrapleural spread of an hepatic hydatid cyst. Right
      posterolateral thoracotomy and frenotomy revealed a loculated pleural effusion
      associated with a 10 x 8 cm hydatid cyst in the posterior segment of the liver.
      Hydatid disease should be included in the differential diagnosis of eosinophilic
      pleural effusions in endemic regions.

PMID- 17539863
TI  - A new method of energy prescription to improve weight loss.
AB  - Clinical outcome audit was carried out on two groups of obese out-patients for a
      3-month follow-up period. In the first audit group of 35 patients (A1), energy
      intake was prescribed by diet history, whereas in the second audit group of 27
      patients (A2) energy intake was prescribed from an estimate of individual energy
      requirements based on age, sex, and activity. There was no significant difference
      in age or initial BMI between the two groups and the failure-to-attend rate was
      the same in each group. Patients in Group A2 received a significantly higher
      energy prescription (P<0.001) than Group A1, but this was still significantly
      more restricted than the recommended 500 kcal energy deficit from energy
      expenditure (P<0.05). Weight loss was significant in both groups, but was greater
      in Group A2 than in Group A1. There was no significant correlation between weight
      loss and energy deficit. In a selected group of patients from Group A2 who were
      prescribed energy intake close to the recommended deficit of 500 kcal, weight
      loss was found to be significantly greater (P<0.05) when compared to the weight
      loss in Group A1. Results suggest that a diet prescription with an energy deficit
      below the estimated energy requirements does not lead to greater weight loss and
      probably reduces compliance. Estimating individual energy requirements rather
      than using dietary assessment may improve weight loss.

PMID- 17539864
TI  - Commentary on Frost, G., Masters, K., King, C., Kelly, M., Hasan, U., Heavens,
      P., White, R. & Stanford, J. (1991) A new method of energy prescription to
      improve weight loss. Journal of Human Nutrition and Dietetics; 4, 369-373.

PMID- 17539865
TI  - Nutrition knowledge, attitudes and fat intake: application of the theory of
      reasoned action.
AB  - Validated questionnaires eliciting information on nutrition knowledge and
      attitudes, related to fat intake from meat, meat products, dairy products and
      fried foods, were completed by 538 subjects. There were high correlations
      (ranging from 0.40 to 0.77) between the sums of belief-evaluations, attitudes,
      intention and self-reported behaviour, with similar correlations for a subgroup
      of males aged 35-54 years. Nutrition knowledge, showed some statistically
      significant (but small) negative correlations with components of attitudes.
      Females had higher nutrition knowledge scores and more negative views of the
      foods than did males. Fat intake, measured using 3 day weighed intakes,
      correlated with self-reported behaviour (r = 0.55, p<0.01) in a subsample of 30
      males, aged 35-54 years. Thus, nutrition knowledge seems less clearly related to
      consumption of these foods than are more specific beliefs and attitudes.

PMID- 17539866
TI  - Commentary on Shepherd, R. & Towler, G. (1992) Nutrition knowledge, attitudes and
      fat intake: application of the theory of reasoned action. Journal of Human
      Nutrition and Dietetics; 5, 387-397.

PMID- 17539867
TI  - Sugars consumption by 379 11-12-year-old English children in 1990 compared with
      results in 1980.
AB  - The amount of sugars consumed by young adolescents was assessed in 1990 using the
      same methods as those employed in a similar survey in 1980. The children were the
      same age (mean 11 years 6 months) and from the same seven schools in both survey.
      In 1980, 405 children completed the study and 379 in 1990. Information was
      collected using two 3-day dietary diaries, each child being interviewed by a
      dietitian upon completion of a diary. The dietitian in this study was calibrated
      closely with the dietitian who undertook the 1980 study so as to ensure
      comparable diet evaluation methods. Total sugars consumption was unchanged (117
      g/day in 1980, 118 g/day in 1990) but consumption of non-milk extrinsic sugars
      increased (83 g/day in 1980, 90 g/day in 1990) and milk and intrinsic sugars
      decreased (34 g/day in 1980, 28 g/day in 1990) between the two surveys. In 1990,
      non-milk extrinsic sugars contributed 17% to total dietary energy intake, while
      milk and intrinsic sugars contributed 5%. There was little difference in percent
      contributions between the sexes, but some social-class trends were apparent.
      Confectionery provided 33% and soft drinks provided 27% of non-milk extrinsic
      sugars, these two dietary sources providing 60% of non-milk extrinsic or 46% of
      total sugars intake. These levels of consumption are considerably higher than
      those currently recommended in the UK.

PMID- 17539868
TI  - Commentary on Rugg-Gunn A.J., Adamson A.J., Appleton D.R., Butler T.J. & Hackett
      A.F. (1993) Sugars consumption by 379 11-12-year-old English children in 1990
      compared with results in 1980. Journal of Human Nutrition and Dietetics; 6, 419
      431.

PMID- 17539869
TI  - Dietary fat and appetite: similarities and differences in the satiating effect of
      meals supplemented with either fat or carbohydrate.
AB  - In experiment 1, normal weight male subjects were provided with three types of
      breakfast consumed in the Human Appetite Research Unit on separate experimental
      days 1 week apart. The intensity of hunger, fullness and other subjective
      feelings were tracked by means of visual analogue rating scales at intervals
      during the day. Energy and nutrient intakes were measured directly from ad
      libitum test meals consumed at lunch and dinner. During the rest of the day and
      until after breakfast the following day, food intake was measured indirectly
      through weighted food records. The test breakfasts comprised a basic meal 184 1
      kJ (440 kcal) and the same meal supplemented with similar amounts of either fat
      (1515 kJ, 362 kcal) or carbohydrate (1527 kJ, 365 kcal). No differences were
      detected between the effects of the basic breakfast compared with the fat
      supplemented breakfast. The carbohydrate supplement suppressed hunger ratings
      during a limited period after consumption (the post-ingestive window coinciding
      with the expected metabolism of carbohydrate. In experiment 2, a direct test of
      consumption during this post-ingestive window confirmed that the carbohydrate
      supplemented breakfast suppressed intake but the fat supplement did not. These
      results demonstrate that carbohydrate and fat can produce quiet different effects
      on satiety. Under these experimental conditions the supplement of fat produced no
      detectable effect on the expression of appetite and illustrates how dietary fat
      could lead to passive over-consumption of energy. However this effect may be
      modified by the particular pattern of food consumption during the course of a
      day.

PMID- 17539870
TI  - Commentary on Cotton, J. R., Burley, V. J., Westrate, J. A. & Blundell, J. E.
      (1994) Dietary fat and appetite: similarities and differences in the satiating
      effect of meals supplemented with either fat or carbohydrate. Journal of Human
      Nutrition and Dietetics; 7, 11-24.

PMID- 17539871
TI  - Nutritionists in industry can play a key role in helping to achieve Health of the
      Nation targets for nutrition.
AB  - Nutritionists working in food manufacturing and retailing are potentially in a
      more powerful position than any other professional group to contribute towards
      achieving the national targets for nutrition and the reduction of nutrition
      related diseases, set out in The Health of the Nation (DoH, 1992) and in
      Scotland's Health, A Challenge to Us All (Scottish Office, 1993). The present
      paper sets out the details of this argument. First, a review is given of the
      functions and types of activities carried out by nutritionists in industry. Then
      a number of key practical ways in which nutritionists, through their activities
      and functions, can help towards achieving national targets for nutrition and
      nutrition-related diseases are described. Finally, suggestions are made about the
      knowledge, skills, and personal attributes needed by nutritionists who intend
      making successful careers in industry and who wish, at the same time, to
      contribute towards improving the health of the nation.

PMID- 17539872
TI  - Commentary on Kirk, T. R., De Looy, A., Fletcher, R. & Ruxton, C. H. (1994)
      Nutritionists in industry can play a key role in helping to achieve Health of the
      Nation targets for nutrition. Journal of Human Nutrition and Dietetics; 7, 295
      300.

PMID- 17539873
TI  - The format for the National Food Guide: performance and preference studies.
AB  - This paper gives the main findings of research designed to inform decisions about
      the format of a food selection guide, subsequently published as the National Food
      Guide. The research involved 2074 members of the public and 230 professionals
      involved in nutrition education. Different formats for the guide were assessed
      for performance (how well the information was understood and recalled) and
      preference with a quota sample of C2 and D socioeconomic groups. Preferences were
      also assessed with a sample of various professionals involved in nutrition
      education. The investigations involved different versions of the guide which
      varied in shape, background colour, presentational style (whether the foods
      depicted were many or few, photographic or drawn) and in the wording of the food
      group headings. The key findings were that exposure to a guide can have a
      significant effect on people's understanding of guide concepts and that some
      aspects of the design enhanced that effect. In particular, guides which were in
      the shape of a tilted plate were better at conveying nutritional concepts than
      those which were pyramid-shaped. Members of the public and nutrition educators
      both preferred a plate shape but, whereas the public preferred a tilted plate to
      a flat plate, the nutrition educators thought that a flat plate would be more
      appealing to their clients than a tilted plate.

PMID- 17539874
TI  - Commentary on Hunt, P., Gatenby, S. and Rayner, M. (1995) The format for the
      National Food Guide: performance and preference studies. Journal of Human
      Nutrition and Dietetics; 8, 335-351.

PMID- 17539875
TI  - Are diets high in non-milk extrinsic sugars conducive to obesity? An analysis
      from the Dietary and Nutritional Survey of British Adults.
AB  - Restriction of dietary sugars is often advocated for weight control, alongside a
      reduced fat and energy intake. This project examined data from the Dietary and
      Nutritional Survey of British Adults (Gregory et al, 1990) to evaluate the
      associations between non-milk extrinsic (NME) sugars (as a percentage of food
      energy) and body mass index (BMI), energy intake and percentage energy from fat.
      The influence of dieting and potential under reporting on these relationships was
      also explored. BMI was inversely associated with percentage energy from NME
      sugars. The relationship was weak, but did not appear to be a mere artifact of
      dieting and/or under reporting. The well-recognized reciprocal relationship
      between sugars energy and fat energy was also seen with saturated,
      monounsaturated and polyunsaturated fatty acids, but not with trans fatty acids.
      As a result of the sugar : fat see saw effect, only 2% of men and women met the
      current dietary targets for both fat and NME sugars, suggesting that these may be
      incompatible on a practical level. These analyses suggest that high (NME) sugar
      diets appear to be weakly related to leanness rather than obesity, although the
      relationship is weaker than the inverse association between sugars and fat. It is
      hypothesized that overweight and diet-restrained individuals often choose to
      restrict NME sugars: a strategy which can result in a higher (proportional) fat
      diet and weight gain. Emphasis on reducing NME sugars intakes may be
      counterproductive to attempts to reduce proportional fat intake and body weight.

PMID- 17539876
TI  - Commentary on Gibson S. A. (1996) Are diets high in non-milk extrinsic sugars
      conducive to obesity? An analysis from the Dietary and Nutritional Survey of
      British Adults. Journal of Human Nutrition and Dietetics; 9, 283-292.

PMID- 17539877
TI  - Three consecutive (1993, 1995, 1997) surveys of food intake, nutritional
      attitudes and knowledge, and lifestyle in 1000 French children, aged 9-11 years.
AB  - BACKGROUND & AIMS: the lifestyle of children in developed societies is
      susceptible to rapid changes and these may affect the nutritional status of
      children. Reduced physical activity and changes in diet have been proposed as
      contributing factors to the growth in childhood overweight and obesity. The aim
      of this study was to assess trends in the food-related behaviour and markers of
      activity/inactivity in French 9-11 year old children. METHODS: Three successive
      surveys (1993, 1995, 1997) were carried out in samples of 1,000 French children,
      aged 9-11 years. Socio-demographic, anthropometric and food-related parameters
      were obtained for each child, using standardized questionnaire administered by
      trained interviewers. RESULTS: previous-day reports of food intake by the child
      revealed a strong persistence of the traditional French meal structure. Breakfast
      was eaten by 97% of children. Over the three surveys, an increasing percentage of
      reported breakfasts contained at least one dairy food, one cereal food, and one
      fruit or juice (from 11% to 17%). Almost all children had lunch, which occurred
      at the school cafeteria for one-third of the subjects. The afternoon snack, a
      traditional meal for French children, was consumed by 86-88% of the samples.
      Almost all children had dinner (99%), most often at home and in the company of
      all family members (73-87%). Lunches and dinners were composed of several courses
      presented in succession, as is usual in France. The foods most preferred by the
      children were often rich in sugar and/or fat (fried potatoes, ice cream, nut
      spread, chocolate, cake, etc). The children could list 'healthy
      foods'competently. They also demonstrated knowledge of terms used in nutrition
      (e.g. calories, fats) and were aware of possible links between intake of certain
      substances and disease. In families of higher socio-economic strata (income,
      education of parents) more time was devoted to sports by the children. Over the
      three surveys, linear trends indicated more exercise time per week and less
      television viewing. A high risk of obesity was likely in very sedentary children
      whose proportion (33%) was stable over the 1993-1997 period. CONCLUSIONS: In
      general the traditional French pattern of eating persisted among these children.
      Although there were signs of movement towards a more complete breakfast, less
      television and more exercise in active children, a substantial proportion of
      children engaged in no sports activity outside school hours. Maintaining
      appropriate weight is therefore difficult in view of the plentiful supply of food
      available to children. Inactive children are at high risk of obesity and should
      be encouraged to adopt a more active lifestyle.

PMID- 17539878
TI  - Commentary on Bellisle, F., Rolland-Cachera, M.F. and the Kellogg Scientific
      Advisory Committee 'Child and Nutrition' (2000) Three consecutive (1993, 1995,
      1997) surveys of food intake, nutritional attitudes and knowledge, and lifestyle
      in 1000 French children, aged 9-11 years. Journal of Human Nutrition and
      Dietetics; 13, 101-111.

PMID- 17539879
TI  - Diet in a group of 18-month-old children in South West England, and comparison
      with the results of a national survey.
AB  - OBJECTIVE: To investigate the normal range of nutrient intakes and food
      consumption patterns in 18 month old children. SUBJECTS: 1,026 children resident
      in South West England, forming part of the Children in Focus (CIF) research
      cohort. METHODS: Diet was assessed using a 3 day unweighed dietary record.
      Nutrient and food intakes were compared with the dietary reference values and
      with the results of a British survey of preschool children -- the National Diet
      and Nutrition Survey (NDNS). RESULTS: Intakes of energy and nearly all nutrients
      were significantly higher in boys than in girls. Intakes of energy were slightly
      above the estimated average requirements. For most nutrients the mean and median
      intakes were well above the Reference Nutrient Intakes (RNI). The exceptions were
      vitamin D, iron and zinc. Nutrient intakes in CIF were very similar to those in
      the NDNS except for carotene, calcium, vitamin D and iodine, where intakes were
      considerably higher in CIF, and sugar intake which was lower in CIF. Intakes of
      most foods were similar in the two surveys. However, consumption of milk, yoghurt
      and fromage frais and baby foods was higher in CIF, intakes of most fruit and
      vegetables was somewhat higher, and intakes of savoury snacks and sugar
      confectionery were lower. In addition, there were differences between the two
      groups in the types of meat and meat products consumed. CONCLUSIONS: These
      children are unlikely to be deficient in any nutrients, with the possible
      exceptions of iron, zinc, and vitamin D. The use of vitamin D supplements and the
      inclusion of iron- and zinc-rich foods in the diets of preschool children should
      be encouraged. These data will be important in assessing the influence of early
      diet on subsequent health and development.

PMID- 17539880
TI  - Commentary on Cowin, I., Emmett, P. and the ALSPAC study team (2000) Diet in a
      group of 18-month-old children in South West England, and comparison with the
      results of a national survey. Journal of Human Nutrition and Dietetics; 13, 87
      100.

PMID- 17539881
TI  - Controlled clinical trial of two weight reducing diets in a NHS hospital dietetic
      outpatient clinic: a pilot study.
AB  - BACKGROUND: Outpatient dietary weight reduction for obesity is unsatisfactory.
      The objective of this study was to compare the efficacy of an energy prescription
      diet with usual care (a healthy eating diet) in adult overweight patients
      referred to a NHS hospital dietetic outpatient clinic, in terms of weight change
      over 12 weeks. METHODS: Controlled clinical trial (systematic allocation).
      RESULTS: Of the 53 patients who attended their first appointment, 27 completed
      the trial. Mean weight loss (kg) after 12 weeks was 4.2 (sd 3.8) on the energy
      prescription diet (n = 16) and 6.0 (sd 2.8) on the healthy eating diet (n = 11).
      CONCLUSIONS: Patients on a weight reducing diet based on energy prescription or
      healthy eating lost, on average, clinically significant amounts of body weight by
      12 weeks. Mean weight loss was greater by about 50% in the healthy eating group
      and supports the development of a larger trial to estimate true effect.

PMID- 17539882
TI  - Commentary on Taylor F. C., Irons L. J., Finn P. & Summerbell C. D. (2003)
      Controlled clinical trial of two weight reducing diets in a NHS hospital dietetic
      outpatient clinic - a pilot study. Journal of Human Nutrition and Dietetics; 16,
      85-87.

PMID- 17539883
TI  - The health benefits of omega-3 polyunsaturated fatty acids: a review of the
      evidence.
AB  - The UK dietary guidelines for cardiovascular disease acknowledge the importance
      of long-chain omega-3 polyunsaturated fatty acids (PUFA) - a component of fish
      oils - in reducing heart disease risk. At the time, it was recommended that the
      average n-3 PUFA intake should be increased from 0.1 to 0.2 g day(-1). However,
      since the publication of these guidelines, a plethora of evidence relating to the
      beneficial effects of n-3 PUFAs, in areas other than heart disease, has emerged.
      The majority of intervention studies, which found associations between various
      conditions and the intake of fish oils or their derivatives, used n-3 intakes
      well above the 0.2 g day(-1) recommended by Committee on Medical Aspects of Food
      Policy (COMA). Furthermore, in 2004, the Food Standards Agency changed its advice
      on oil-rich fish creating a discrepancy between the levels of n-3 PUFA implied by
      the new advice and the 1994 COMA guideline. This review will examine published
      evidence from observational and intervention studies relating to the health
      effects of n-3 PUFAs, and discuss whether the current UK recommendation for long
      chain n-3 PUFA needs to be revisited.

PMID- 17539884
TI  - Commentary on Ruxton, C. H. S., Reed, S. C., Simpson, M. J. A. & Millington, K.
      J. (2004) The health benefits of omega-3 polyunsaturated fatty acids: a review of
      the evidence. Journal of Human Nutrition and Dietetics; 17, 449-459.

PMID- 17539885
TI  - Does birth spacing affect maternal or child nutritional status? A systematic
      literature review.
AB  - This review addresses the question of whether a short birth interval is
      associated with adverse nutritional outcomes for the mother or the child. Indices
      of anthropometric status (maternal weight or body mass index; child growth) and
      micronutrient status (e.g. iron or vitamin A) were included as outcomes. A
      computerized search of all relevant papers published since 1966 was completed,
      and the 'snowball' method was used to identify additional relevant published or
      unpublished papers. In total, 57 papers were found to contain data regarding the
      relationship between birth spacing and nutritional outcomes (35 for child
      nutrition, 11 for maternal anthropometric status, and 11 for maternal anaemia or
      micronutrient status). Of these, 23 papers were excluded from further
      consideration because they did not include any multivariate analysis, leaving 34
      papers that met the criteria for the review (22 for child nutrition, eight for
      maternal anthropometric status, and four for maternal anaemia or micronutrient
      status). The studies on child nutrition outcomes indicate that a longer birth
      interval is associated with a lower risk of malnutrition in some populations, but
      not all. In those countries in which the relationship was significant, the
      reduction in stunting associated with a previous birth interval >or=36 months
      ranged from approximately 10% to 50%. Some of this reduction may be due to
      residual confounding, i.e. to factors not included in the analysis (such as
      breastfeeding and maternal height). The studies on maternal anthropometric
      outcomes yielded mixed results. Because the nutritional burden on the mother
      between pregnancies depends on the extent of breastfeeding, the interpregnancy
      interval is not the best measure of whether the mother has had a chance to
      recover from the pregnancy, in terms of repleting her nutritional status.
      Therefore, some studies examined the 'recuperative interval' (duration of the non
      pregnant, non-lactating interval) instead. Taken as a whole, the studies do not
      provide clear evidence of a link between interpregnancy or recuperative interval
      and maternal anthropometric status. This may be due, in part, to changes in the
      hormonal regulation of nutrient partitioning between the mother and the fetus
      when a mother is malnourished. Only four papers were identified that related to
      micronutrient status, three of which examined maternal anaemia. One study showed
      an increased risk for maternal anaemia when the interpregnancy interval was <6
      months, but the analysis did not control for iron supplementation during
      pregnancy. The other two studies did not show a significant association between
      interpregnancy interval and maternal anaemia. One study of micronutrient status
      indicated no significant relationship between interpregnancy interval and
      maternal serum zinc, copper, magnesium, ferritin, folate or thyroid-stimulating
      hormone. Important methodological limitations were apparent in most of the
      studies. Thus, further research with more comprehensive control of potentially
      confounding variables is needed.

PMID- 17539886
TI  - Preterm delivery but not intrauterine growth retardation is associated with young
      maternal age among primiparae in rural Nepal.
AB  - Pregnancy during adolescence is associated with adverse birth outcomes, including
      preterm delivery and low birthweight. The nutrient availability to the fetus may
      be limited if the mother is still growing. This research aims to study the
      effects of pregnancy during adolescence in a nutritionally poor environment in
      rural Nepal. This study utilized data from a randomized controlled trial of
      micronutrient supplementation during pregnancy in south-eastern Nepal. Women of
      parity 0 or 1 and of age <or= 25 years who gave birth to a singleton liveborn
      infant who was measured within 72 h of delivery were included (n = 1393). There
      was no difference in the risk of low birthweight (OR = 0.96; 95% CI = 0.90-1.02)
      or small for gestational age (OR = 1.01; 95% CI = 0.94-1.08) per year of
      increasing maternal age among primiparae. Young maternal age did not affect the
      anthropometry or gestational age of the offspring of parity 1 women. Each year of
      increasing maternal age among primiparae was associated with increases in birth
      length (0.07 cm; 95% CI = -0.01 to 0.16), head (0.05 cm; 95% CI = 0.01-0.09) and
      chest circumference (0.07 cm; 95% CI = 0.01-0.12), but not weight (9.0 g; 95% CI
      = -2.1 to 21.8) of their offspring. Young maternal age was associated with an
      increased risk of preterm delivery among primiparae (OR = 2.07; 95% CI = 1.26
      3.38) that occurred at an age cut-off of <or=18 years relative to those 19-25
      years. Thus, we conclude that young maternal age (<or=18 years) increased the
      risk of preterm delivery, but not intrauterine growth retardation, for the first
      but not second liveborn infant.

PMID- 17539887
TI  - Predictors of delayed onset of lactation.
AB  - The objective of this study was to identify biomedical and hospital-related
      factors associated with the delayed onset of lactation (>72 h postpartum) in a
      population of Australian women. Subjects were 453 women participating in the
      second Perth Infant Feeding Study. Information on mothers' perception of the
      timing of the onset of lactation and associated explanatory factors was collected
      in a questionnaire completed by women prior to or shortly after discharge from
      hospital. Multivariate logistic regression was used to identify those factors
      independently associated with delayed lactation. Risk factors for delayed
      lactation were being primiparous (adjusted OR 3.16, 95% CI 1.58-6.33) and having
      delivered by caesarean section (adjusted OR 2.40, 95% CI 1.28-4.51). We failed to
      find a negative association with maternal body mass index reported in previous
      studies. While a greater proportion of women who experienced delayed lactation
      were overweight or obese compared with those who did not experience delayed
      lactation (40.8% vs. 32.1%), this difference was not statistically significant.

PMID- 17539888
TI  - Breastfeeding Best Start study: training midwives in a 'hands off' positioning
      and attachment intervention.
AB  - The most common reasons cited by women for giving up breastfeeding early can be
      attributed to ineffective positioning and attachment and are therefore
      preventable. This study aimed to determine whether a 4-h training programme in
      'hands off' positioning and attachment support increases midwives' knowledge and
      problem-solving skills. Using an unrelated comparison group and a pre- and post
      intervention design, 108 midwives (experimental group) completed a 4-h standard
      breastfeeding training workshop focusing on effective positioning and attachment
      and the use of hands-off teaching methods. Knowledge and problem-solving skills
      were assessed using a modified form of the previously validated Breastfeeding
      Support Skills Tool. Pre- and post-training scores were compared with those of 27
      student midwives (control group) who undertook the same assessments but without
      the breastfeeding training. Baseline knowledge scores of the midwives and the
      student midwives did not differ significantly (average difference 0.7 points to
      qualified midwives' advantage, 95% CI = -3.4 to 1.9). Following training, the
      qualified midwives' total scores increased significantly (7.2 points, 95% CI =
      6.2-8.2). Minimal changes (1.4 points, 95% CI = -0.15 to 2.9) in students' scores
      were found. The additional increase owing to training above that which might be
      expected due to practice (i.e. the average difference in change scores between
      the two groups) was 5.8 points (95% CI = 3.75-7.96), representing a large effect
      size for the training (d = 0.95). There is a large variation in the breastfeeding
      knowledge of midwives working in post-natal care and, on average, they are no
      more skilled than senior student midwives. The study has shown that a 4-h
      workshop in a positioning and attachment intervention, using a 'hands-off'
      approach, can increase midwives' knowledge of breastfeeding support relevant to
      the immediate post-natal period. It is applicable to all midwives, and could be a
      cost-effective way of improving the ability of mothers to begin and continue to
      breastfeed successfully.

PMID- 17539889
TI  - A large-scale operational study of home-based therapy with ready-to-use
      therapeutic food in childhood malnutrition in Malawi.
AB  - Home-based therapy with ready-to-use therapeutic food (RUTF) for the treatment of
      malnutrition has better outcomes in the research setting than standard therapy.
      This study examined outcomes of malnourished children aged 6-60 months enrolled
      in operational home-based therapy with RUTF. Children enrolled in 12 rural
      centres in southern Malawi were diagnosed with moderate or severe malnutrition
      according to the World Health Organization guidelines. They were treated with 733
      kJ kg(-1) day(-1) of RUTF and followed fortnightly for up to 8 weeks. Staff at
      each centre followed one of three models: medical professionals administered
      treatment (5 centres), patients were referred by medical professionals and
      treated by community health aids (4 centres), or community health aids
      administered treatment (3 centres). The primary outcome of the study was clinical
      status, defined as recovered, failed, died or dropped out. Regression modelling
      was conducted to determine what aspects of the centre (formal training of staff,
      location along a main road) contributed to the outcome. Of 2131 severely
      malnourished children and 806 moderately malnourished, 89% and 85% recovered,
      respectively. Thirty-four (4%) of the moderately malnourished children failed,
      with 20 (2%) deaths, and 61 (3%) of the severely malnourished children failed,
      with 29 (1%) deaths. Centre location along a road was associated with a poor
      outcome. Outcomes for severely malnourished children were acceptable with respect
      to both the Sphere guidelines and the Prudhon case fatality index. Home-based
      therapy with RUTF yields acceptable results without requiring formally medically
      trained personnel; further implementation in comparable settings should be
      considered.

PMID- 17539890
TI  - Stunting, underweight and wasting among Integrated Child Development Services
      (ICDS) scheme children aged 3-5 years of Chapra, Nadia District, West Bengal,
      India.
AB  - This study investigated age and sex variations in height and weight, levels of
      stunting, underweight and wasting among 533 (254 boys; 279 girls) 3- to 5-year
      old rural children of Bengalee ethnicity at 11 Integrated Child Development
      Services centres of Nadia District, West Bengal, India. Height-for-age, weight
      for-age and weight-for-height < -2 z-scores were used to evaluate stunting,
      underweight and wasting, respectively, following the National Center for Health
      Statistics (NCHS) Guidelines. Results revealed that boys were significantly
      heavier than girls at age 3 years. Significant age differences existed in mean
      height and weight in both sexes. Mean z-scores of height-for-age, weight-for-age
      and weight-for-height were lower than those of NCHS for both sexes at all ages.
      The overall (age and sex combined) rates of stunting, underweight and wasting
      were 23.9%, 31.0% and 9.4%, respectively. The rate of underweight and wasting was
      higher among girls (underweight = 35.1%, wasting = 12.2%) compared with boys
      (underweight = 26.5%, wasting = 6.3%). In general, the frequency of stunting
      increased with increasing age in both sexes. Based on the World Health
      Organization classification of severity of malnutrition, the overall prevalence
      of underweight was very high (>or=30%). The prevalence rates of stunting (20-29%)
      and wasting (5-9%) were medium. In conclusion, the nutritional status of the
      subjects is unsatisfactory. There is scope for improvement in the form of
      enhanced supplementary nutrition.

PMID- 17539891
TI  - Corticotropin-releasing factor receptor 1-deficient mice show decreased anxiety
      and colonic sensitivity.
AB  - Corticotropin releasing factor (CRF) is an important mediator in the stress
      response. Previous studies in rodent models demonstrated that stress-induced
      colonic hypersensitivity was inhibited by CRF1 receptor antagonism. As CRF(1)R
      deficient mice have (+/+), CRF(1)R (+/-) and CRF(1)R (-/-) mice colonic
      sensitivity was assessed via a visceromotor behavioural response (VMR) induced by
      colorectal distension (CRD, 0-60 mmHg). In the CRF(1)R (+/+) mice there was a
      pressure-dependent increase in the VMR to CRD that was moderately attenuated in
      the CRF1R (+/-) mice. However in the CRF(1)R (-/-) mice a VMR to CRD was only
      observed at the highest distension pressure (60 mmHg). A CRF(1)R antagonist, NBI
      30775 (30 mg kg(-1) i.p.) significantly decreased the VMR to CRD in CRF(1)R +/+
      mice. An identical inhibitory effect of NBI 30775 was observed in 43% of the
      CRF(1)R +/- mice. This study provides pharmacological and genetic evidence for
      the importance of CRF(1)R in colonic sensitivity and suggests a link between
      stress and visceral perception.

PMID- 17539892
TI  - Activation of the cannabinoid 2 (CB2) receptor inhibits murine mesenteric
      afferent nerve activity.
AB  - Abstract Cannabinoid 2 (CB2) receptors have both antinociceptive and
      antihypersensitivity effects, although the precise mechanisms of action are still
      unclear. In this study, the modulatory role of CB2 receptors on the mesenteric
      afferent response to the endogenous immunogenic agent bradykinin (BK) was
      investigated. Mesenteric afferent recordings were obtained from anaesthetized
      wild-type and CB2(-/-) mice using conventional extracellular recording
      techniques. Control responses to BK were obtained in all experiments prior to
      administration of either CB2 receptor agonist AM1241, or AM1241 plus the CB2
      receptor antagonist AM630. Bradykinin consistently evoked activation of
      mesenteric afferents (n = 32). AM1241 inhibited the BK response in a dose
      dependent manner. In the presence of AM630 (10 mg kg(-1)), however, AM1241 (10 mg
      kg(-)1) had no significant effect on the BK response. Moreover, AM1241 had also
      no significant effect on the BK response in CB2(-/-) mice. Activation of the CB2
      receptor inhibits the BK response in mesenteric afferents, demonstrating that the
      CB2 receptor is an important regulator of neuroimmune function. This may be a
      mechanism of action for the antinociceptive and antihypersensitive effects of CB2
      receptor agonists.

PMID- 17539893
TI  - TRPV1 in colitis: is it a good or a bad receptor?--a viewpoint.
AB  - The role of the transient receptor potential vanilloid-1 (TRPV1) has been
      repeatedly investigated in animal models of inflammation. The present issue of
      Neurogastroenterology and Motility includes another report on this issue and, not
      unexpectedly, many questions on the precise role of TRPV1 receptors in
      inflammation remain unanswered. This Editorial Viewpoint discusses the present
      knowledge on TRPV1 receptor involvement in intestinal inflammation and discusses
      the question whether the TRPV1 has to be regarded as the good or the bad receptor
      in this context. Since TRPV1 activation turns out being a valuable approach,
      translation of this knowledge to human disease is highly recommended.

PMID- 17539894
TI  - Does co-administration of a non-selective opiate antagonist enhance acceleration
      of transit by a 5-HT4 agonist in constipation-predominant irritable bowel
      syndrome? A randomized controlled trial.
AB  - Opioid neurons exhibit tonic restraint on intestinal motility; opioid antagonists
      stimulate peristalsis and increase transit. In vitro, 5-hydroxytryptamine (5-HT4)
      agonists combined with selective opioid antagonists significantly increased
      colonic propulsion relative to a 5-HT4 agonist alone. We hypothesized that the
      combination of 5-HT4 agonist and non-selective opioid antagonist enhances
      intestinal transit more than either treatment alone in female constipation
      predominant irritable bowel syndrome (C-IBS) patients. Our aim was to examine the
      effect of tegaserod 6 mg b.i.d. alone and combined with naltrexone 50 mg on
      intestinal transit and stool characteristics in females with C-IBS. Forty-eight
      patients were randomized to tegaserod alone, naltrexone alone or in combination
      with tegaserod or placebo for 6 days. Small bowel, ascending colon half-life (in
      pharmacokinetics) (t1/2), and colonic geometric centre (8, 24, 48 h) were
      assessed by scintigraphy. Tegaserod increased small bowel (P < 0.01) and colon
      transit (P < 0.01). Naltrexone did not accelerate colonic transit relative to
      placebo. Combination treatment did not significantly accelerate transit relative
      to tegaserod alone. Tegaserod and tegaserod with naltrexone resulted in looser
      stool form (P < 0.01). In female C-IBS patients, tegaserod accelerates small
      bowel and colon transit and contributed to looser stool consistency. Use of
      naltrexone, 50 mg, does not support the hypothesis that combination of 5-HT4
      agonist and non-selective opioid antagonist enhances intestinal transit.

PMID- 17539895
TI  - Sigmoid-colonic motility in health and irritable bowel syndrome: a role for 5
      hydroxytryptamine.
AB  - Abstract Evidence suggests that sigmoid-colonic motility is increased in patients
      with irritable bowel syndrome (IBS). 5-Hydroxytryptamine (5-HT) plays a role in
      the control of motility, but its involvement in the dysmotility seen in IBS
      remains unclear. To investigate the relationship between platelet depleted plasma
      5-HT (PDP 5-HT) concentration and sigmoid-colonic motility in patients with IBS
      and healthy volunteers. Pre- and postprandial PDP 5-HT concentrations were
      assessed while recording sigmoid-colonic motility in 35 IBS patients (aged 19-53
      years, eight male) and 16 healthy volunteers (aged 18-39 years, six male).
      Motility was recorded using a five-channel solid-state catheter introduced to a
      depth of 35 cm into an unprepared bowel. 5-Hydroxytryptamine concentration was
      measured by reverse-phase HPLC with fluorimetric detection. Irritable bowel
      syndrome patients had elevated concentrations of PDP 5-HT under fasting (P <
      0.004) and fed (P = 0.079) conditions compared with controls. Likewise, they
      exhibited increased sigmoid-colonic motility under fasting (activity index: P <
      0.02) and fed (P < 0.05) conditions compared with controls. Platelet depleted
      plasma 5-HT concentration positively correlated with colonic activity index under
      both fasting (r = 0.402; P = 0.003) and fed (r = 0.439; P = 0.001) conditions.
      These data show a possible relationship between endogenous concentrations of 5-HT
      and sigmoid-colonic motility recorded in both IBS and healthy subjects.

PMID- 17539896
TI  - Effects of NMDA receptor antagonists on visceromotor reflexes and on intestinal
      motility, in vivo.
AB  - Antagonists of NMDA receptors can inhibit both the transmission of pain signals
      from the intestine and enteric reflexes. However, it is unknown whether doses of
      the NMDA antagonist, ketamine, that are used in anaesthetic mixtures suppress
      motility reflexes and visceromotor responses (VMRs). In fact, whether intestinal
      motility is affected by NMDA receptor blockers in vivo has been little
      investigated. We studied the effects of ketamine and memantine, administered
      intravenously or intrathecally. Rats were maintained under alpha-chloralose plus
      xylazine or pentobarbitone anaesthesia; VMR and jejunal motility were measured.
      Under alpha-chloralose/xylazine anaesthesia, i.v. ketamine inhibited VMRs at 6 mg
      kg h(-1), but not at 3 mg kg h(-1). It did not inhibit propulsive reflexes in the
      jejunum at 10 mg kg h(-1), but reduced them by 30% at 20 mg kg h(-1). Under alpha
      chloralose/pentobarbitone anaesthesia, i.v. ketamine reduced propulsive reflexes
      at 40 mg kg h(-1) and VMR at 10 mg kg h(-1). Memantine inhibited VMRs at 20 mg kg
      h(-1) and propulsion at 2 mg kg h(-1). Ketamine and memantine, intrathecally,
      prevented VMRs, but not jejunal propulsion. We conclude that peripherally
      administered ketamine reduces both VMR and motility reflexes, but not at doses
      used in anaesthetic mixes (1.8-2.4 mg kg h(-1)). Effects on motility reflexes are
      likely to be due to non-NMDA receptor actions, possibly on nicotinic receptors.

PMID- 17539897
TI  - Constitutive deficiency in DNA mismatch repair.
AB  - Mutations in the DNA mismatch repair (MMR) genes are associated with the
      inheritance of hereditary non-polyposis colorectal cancer, also known as Lynch
      syndrome, a cancer syndrome with an average age at onset of 44. Individuals
      presenting with colorectal cancer are diagnosed with Lynch I, whereas individuals
      who present with extra-colonic tumors (such as endometrial, stomach, etc.) are
      identified as patients with Lynch syndrome II. Recently, 30 families have been
      reported with inheritance of biallelic mutations in the MMR genes. Here we
      summarize the phenotype of individuals with inheritance of homozygous or compound
      heterozygous mutations in the MMR genes that result in a complete lack of protein
      or greatly compromised protein function. In contrast to individuals with Lynch
      syndrome I and II, individuals with no MMR function present with childhood onset
      of hematological and brain malignancies, whereas residual MMR function can also
      result in gastrointestinal cancers and an age of onset in the second to fourth
      decade. Individuals with biallelic MMR mutations often present with cafe-au-lait
      spots, regardless of the level of MMR function remaining. Thus, the inheritance
      of two MMR gene mutations is a separate entity from Lynch I or II or the subtypes
      Turcot and Muir-Torre.

PMID- 17539898
TI  - Constitutive deficiency in DNA mismatch repair: is it time for Lynch III?
AB  - Hereditary non-polyposis colorectal cancer (HNPCC), also known as Lynch syndrome
      types I and II, and the related subtypes Turcot and Muir-Torre syndrome, have all
      been associated with inheritance of germ line mutations in the DNA mismatch
      repair (MMR) genes. Fifty individuals have recently been identified with an early
      onset of a different spectrum of cancers associated with inheritance of two MMR
      mutations--resulting either in a constitutive loss of MMR function, or greatly
      impaired MMR function. In contrast to Lynch I and II individuals, individuals
      with inheritance of homozygous or compound heterozygous mutations in the MMR
      genes that result in a complete lack of protein, present with hematological and
      brain malignancies in the first decade of life. Biallelic mutations with
      compromised but residual protein function present with a broader spectrum of
      cancers (brain, hematological or gastrointestinal) in the second to fourth
      decades of life. We propose that inheritance of two MMR mutations in an
      individual and the unique tumor spectrum that occurs with an early onset should
      be defined separately from Lynch syndrome I and II, or the subtypes Turcot and
      Muir-Torre. We suggest Lynch III as an appropriate name for identifying
      individuals with constitutively compromised MMR associated with biallelic
      mutations.

PMID- 17539899
TI  - Genetic testing for heart disease susceptibility: potential impact on motivation
      to quit smoking.
AB  - As genetic tests for common gene variants and multifactorial, lifestyle-related
      conditions become available, it will be increasingly important to determine the
      psychological and behavioral impact of this emerging class of genetic tests. Our
      aim was to examine the potential impact of genetic testing for heart disease
      susceptibility on psychological predictors of smoking cessation. Two hundred and
      sixty-one smokers were asked to imagine that they had undergone a test for heart
      disease risk. They were randomly assigned to a genetic test scenario (low- or
      high-risk result) or an oxidative test scenario (high-risk result). Smokers in
      the genetic test-high risk group reported greater intention to quit smoking than
      smokers in the oxidative test-high risk group (p = 0.009); 30% of this was
      mediated by their holding stronger beliefs that quitting would reduce their heart
      disease risk (outcome expectations) (p = 0.011). The effect of genetic test-high
      risk feedback on outcome expectations was greatest amongst smokers with no heart
      disease family history (p = 0.038). The results suggest that genetic testing for
      heart disease risk may enhance interventions designed to improve health via
      increasing smoking cessation rates. Whether the findings hold true in studies
      that use real rather than hypothetical genetic tests remains to be seen.

PMID- 17539900
TI  - Abnormal brain structure in adults with Van der Woude syndrome.
AB  - Van der Woude syndrome (VWS) is an autosomal dominant disorder manifested in
      cleft lip and/or palate and lip pits. Isolated clefts of the lip and/or palate
      (ICLP) have both genotype and phenotype overlap with VWS. Subjects with ICLP have
      abnormalities in brain structure and function. Given the similarities between VWS
      and ICLP, the current study was designed to evaluate the pattern of brain
      structure of adults with VWS. Fourteen adults with VWS were compared to age- and
      gender-matched healthy controls. Brain structure was evaluated using magnetic
      resonance imaging. All subjects with VWS had enlarged volumes of the anterior
      regions of the cerebrum. Men with VWS had reduced volumes of the posterior
      cerebrum. Anterior cerebrum volume was negatively correlated with intelligent
      quotient in the subjects with VWS indicating that the enlargement of this brain
      region was 'pathologic.' The pattern of brain structure in VWS is nearly
      identical to those seen in ICLP. In addition, men are affected more severely.
      Pathologic enlargement of the tissue and a gender effect with men affected more
      severely are common features of neurodevelopmental disorders supporting the
      notion that the brain structure of VWS and ICLP may be because of abnormal brain
      development.

PMID- 17539901
TI  - A genome-wide linkage scan for iron phenotype quantitative trait loci: the HEIRS
      Family Study.
AB  - Iron overload phenotypes in persons with and without hemochromatosis are
      variable. To investigate this further, probands with hemochromatosis or evidence
      of elevated iron stores and their family members were recruited for a genome-wide
      linkage scan to identify potential quantitative trait loci (QTL) that contribute
      to variation in transferrin saturation (TS), unsaturated iron-binding capacity
      (UIBC), and serum ferritin (SF). Genotyping utilized 402 microsatellite markers
      with average spacing of 9 cM. A total of 943 individuals, 64% Caucasian, were
      evaluated from 174 families. After adjusting for age, gender, and race/ethnicity,
      there was evidence for linkage of UIBC to chromosome 4q logarithm of the odds
      (LOD) = 2.08, p = 0.001) and of UIBC (LOD = 9.52), TS (LOD = 4.78), and SF (LOD =
      2.75) to the chromosome 6p region containing HFE (each p < 0.0001). After
      adjustments for HFE genotype and other covariates, there was evidence of linkage
      of SF to chromosome 16p (LOD = 2.63, p = 0.0007) and of UIBC to chromosome 5q
      (LOD = 2.12, p = 0.002) and to chromosome 17q (LOD = 2.19, p = 0.002). We
      conclude that these regions should be considered for fine mapping studies to
      identify QTL that contribute to variation in SF and UIBC.

PMID- 17539902
TI  - Spectrum of mutations and variants/haplotypes of CFTR and genotype-phenotype
      correlation in idiopathic chronic pancreatitis and controls in Chinese by
      complete analysis.
AB  - Mutations in cystic fibrosis transmembrane conductance regulator (CFTR) gene have
      been reported in patients with chronic pancreatitis. The authors examine whether
      the mutations and haplotypes of CFTR will increase the risk of developing
      idiopathic chronic pancreatitis (ICP) in Chinese and their genotype and phenotype
      correlations. Seventy-eight patients with ICP and 200 geographically and
      ethnically matched controls in Taiwan were analyzed. The entire 27 coding and
      intronic regions of the CFTR gene were identified using heteroduplex analytical
      techniques and confirmed by sequencing analysis. The presence of 125G/C,
      1001+10C>T, IVSTn(TG)m, 1540A>G, c2694T>G, and c4521G>A were determined by
      directing sequencing. Abnormal CFTR allele was found to be thrice as frequent in
      ICP patients as in controls (22/156 vs 19/400, p < 0.0001). T5 allele was
      associated with early onset of ICP. In six-loci haplotype analysis, 13 common
      haplotypes were assembled in the 278 individuals tested. The
      125G/1001+11C/TG12/470M/2694T/4521G haplotype was associated with risk of ICP
      (odds ratio 11.3; 95% confidence interval 2.3-54.6, p = 0.008) in Chinese. The
      mutation spectrum is different from other ethnic groups. A population-specific
      panel of CFTR changes should be recommended for targeted populations including
      ICP in Chinese. It is important to design suitable screening programs for
      different populations.

PMID- 17539903
TI  - Gender, genotype, and phenotype differences in Smith-Magenis syndrome: a meta
      analysis of 105 cases.
AB  - Smith-Magenis syndrome (SMS) is a multisystem disorder characterized by
      developmental delay and mental retardation, a distinctive behavioral phenotype,
      and sleep disturbance. We undertook a comprehensive meta-analysis to identify
      genotype-phenotype relationships to further understand the clinical variability
      and genetic factors involved in SMS. Clinical and molecular information on 105
      patients with SMS was obtained through research protocols and a review of the
      literature and analyzed using Fisher's exact test with two-tailed p values.
      Several differences in these groups of patients were identified based on genotype
      and gender. Patients with RAI1 mutation were more likely to exhibit overeating,
      obesity, polyembolokoilamania, self-hugging, muscle cramping, and dry skin and
      less likely to have short stature, hearing loss, frequent ear infections, and
      heart defects when compared with patients with deletion, while a subset of small
      deletion cases with deletions spanning from TNFRSF13B to MFAP4 was less likely to
      exhibit brachycephaly, dental anomalies, iris abnormalities, head-banging, and
      hyperactivity. Significant differences between genders were also identified, with
      females more likely to have myopia, eating/appetite problems, cold hands and
      feet, and frustration with communication when compared with males. These results
      confirm previous findings and identify new genotype-phenotype associations
      including differences in the frequency of short stature, hearing loss, ear
      infections, obesity, overeating, heart defects, self-injury, self-hugging, dry
      skin, seizures, and hyperactivity among others based on genotype. Additional
      studies are required to further explore the relationships between genotype and
      phenotype and any potential discrepancies in health care and parental attitudes
      toward males and females with SMS.

PMID- 17539904
TI  - Glucose metabolism and insulin secretion in a patient with ABCC8 mutation and
      Fanconi-Bickel syndrome caused by maternal isodisomy of chromosome 3.
AB  - Fanconi-Bickel syndrome (FBS) is a rare disorder of glucose transport caused by
      autosomal recessive mutations in GLUT2. Clinically, FBS results in growth
      failure, hepatomegaly, renal Fanconi syndrome, and abnormal glucose homeostasis.
      We report a 23 month old female with FBS characterized by more severe and
      refractory hypoglycemia than typically seen in this disorder. Although previous
      reports indicate that FBS patients have diminished insulin secretion, our patient
      showed evidence of hyperinsulinism (HI). Sequence analysis showed that the
      patient was homozygous for a known null mutation in GLUT2, confirming the
      clinical diagnosis of FBS. Parental genotyping showed that the mother was
      heterozygous for the GLUT2 mutation, while the father was wild type. Tandem
      repeat marker analysis showed that the patient inherited the GLUT2 mutation via
      maternal isodisomy of chromosome 3. Further molecular testing showed that the
      patient was heterozygous for a mutation in ABCC8, a known cause of congenital HI.
      We discuss the patient's biochemical responses in light of the molecular
      findings.

PMID- 17539905
TI  - Aplasia cutis congenita, congenital heart lesions, and frontonasal cysts in four
      successive generations.
AB  - We report a family with four known generations of individuals in the maternal
      family tree with aplasia cutis congenita (ACC) of the scalp, congenital heart
      lesions, brachydactyly, and frontonasal cysts. This is the first reported finding
      of craniofacial, digital, and cardiac abnormalities associated with ACC, likely
      representing a new variant of the autosomal dominant hidrotic ectodermal
      dysplasia subtype. These rare disorders are characterized by common anomalies of
      at least two elements of the ectoderm and its appendages, namely the skin, teeth,
      hair, nails, and sweat glands. These patients also frequently have chronic dental
      problems with early loss of teeth, and recurrent lung, ear, and nose infections
      secondary to a defect in mucous membrane function. The clinical findings in these
      patients are delineated and compared to patients with other forms of ectodermal
      dysplasia in the literature.

PMID- 17539906
TI  - Multiplex ARMS analysis to detect 13 common mutations in familial
      hypercholesterolaemia.
AB  - DNA analysis and mutation identification is useful for the diagnosis of familial
      hypercholesterolaemia (FH), particularly in the young and in other situations
      where clinical diagnosis may be difficult, and enables unambiguous identification
      of at-risk relatives. Mutation screening of the whole of the three FH-causing
      genes is costly and time consuming. We have tested the specificity and
      sensitivity of a recently developed multiplex amplification refractory mutation
      system assay of 11 low-density lipoprotein receptor gene (LDLR) mutations, one
      APOB (p.R3527Q) and one PCSK9 (p.D374Y) mutation in 400 patients attending 10 UK
      lipid clinics. The kit detected a mutation in 54 (14%) patients, and a complete
      screen of the LDLR gene using single-stranded conformation
      polymorphism/denaturing high performance liquid chromatography identified 59
      different mutations (11 novel) in an additional 87 patients, for an overall
      detection rate of 35%. The kit correctly identified 38% of all detected mutations
      by the full screen, with no false-positive or false-negative results. In the
      patients with a clinical diagnosis of definite FH, the overall detection rate was
      higher (54/110 = 49%), with the kit detecting 52% of the full-screen mutations.
      Results can be obtained within a week of sample receipt, and the high detection
      rate and good specificity make this a useful initial DNA diagnostic test for UK
      patients.

PMID- 17539907
TI  - Assessment of the prevalence of the 985A>G MCAD mutation in the French-Canadian
      population using allele-specific PCR.
AB  - Inherited deficiency of medium-chain acyl-CoA dehydrogenase (MCAD) is a severe,
      sometimes fatal disorder. A single mutation in the MCAD gene, 985A>G, is involved
      in approximately 90% of cases. To evaluate the relevance of implementing a
      systematic population-based screening program in the province of Quebec using a
      biochemical test, we measured the prevalence of this mutation in a set of
      anonymous newborn samples from the Quebec City area, a region where the majority
      of its inhabitants are French-Canadians. An allele-specific polymerase chain
      reaction assay was designed and used to detect the mutation in 7143 DNA samples
      obtained from consecutive anonymous newborns. Pools of eight DNA samples were
      genotyped in parallel for the same mutation to validate this pooling strategy.
      The allelic frequency of the MCAD 985A>G mutation was found to be 0.71% and the
      carrier frequency 1:71 (95% confidence interval 1:55 to 1:98). This estimate
      predicts a homozygous frequency of 1:19,837. Ninety-nine heterozygous carriers
      and one homozygous individual were identified out of 7143 samples. There was 100%
      concordance between the individual and pooled analyses, and the pooling strategy
      reduced the total genotyping costs by approximately 70%. The carrier frequency
      estimated for this population is similar to other northwestern European
      populations and would support implementation of systematic newborn screening
      (such as tandem mass spectrometry screening) for this disease. Pooling DNA
      samples followed by genotyping appears to be cost-effective for estimating
      prevalence of rare mutations.

PMID- 17539908
TI  - Imiglucerase (Cerezyme) improves quality of life in patients with skeletal
      manifestations of Gaucher disease.
AB  - Health-related quality of life (HRQOL) can be diminished in patients with type 1
      Gaucher disease (GD) owing to the debilitating clinical manifestations of this
      chronic disease. This study investigates the impact of imiglucerase treatment on
      HRQOL of patients with type 1 GD and bone involvement. Thirty-two previously
      untreated type 1 GD patients with skeletal manifestations including bone pain,
      medullary infarctions, avascular necrosis, and lytic lesions received biweekly
      imiglucerase (at 60 U/kg). The Short Form-36 Health Survey (SF-36) was
      administered at regular intervals to assess HRQOL. Mean baseline SF-36 physical
      component summary (PCS) scores were diminished relative to US general population
      norms. Low PCS scores were more common in patients with medullary infarction,
      lytic lesions, and higher bone pain severity scores. Statistically significant
      improvements were observed for all eight SF-36 subscales after 2 years of
      treatment. Mean PCS and mental component summary (MCS) scores increased to within
      the normal range after 2 years of treatment and were maintained through year 4.
      Large HRQOL gains were observed even in patients with the most advanced disease
      and lowest baseline PCS scores. Imiglucerase treatment has a significant positive
      impact on HRQOL of type 1 GD patients with skeletal disease, including those with
      bone infarctions, lytic lesions, and avascular necrosis.

PMID- 17539909
TI  - The presence of germ line mosaicism in cleidocranial dysplasia.
AB  - Cleidocranial dysplasia (CCD) is typically an autosomal dominant condition. The
      possibility of alternative causes, such as an autosomal recessive form or germ
      line mosaicism, have been suggested in some families with CCD, but not proven. We
      present a family consisting of a mother having three sons affected with CCD. One
      of the affected boys is a half brother to the other two affected children. The
      diagnosis of CCD was confirmed by DNA analysis of the RUNX2 gene in all three of
      the boys in blood; however, initial DNA testing in the mother's blood did not
      detect the presence of a RUNX2 mutation in the mother. Further testing through
      heteroduplex analysis applying high-resolution melting analysis followed by
      subcloning detected low-level mosaicism in DNA isolated from maternal blood and
      buccal swab, confirming low-level mosaicism in somatic cells. We present the
      first case of confirmed germ line mosaicism in CCD.

PMID- 17539910
TI  - The position of the mutation within the LMNA gene determines the type and extent
      of tissue involvement in laminopathies.

PMID- 17539912
TI  - Isolated cystinuria (OMIM 238200) is not a separate entity but is caused by a
      mutation in the cystinuria gene SLC7A9.

PMID- 17539913
TI  - Schizophrenia in a patient with subtelomeric duplication of chromosome 22q.

PMID- 17539914
TI  - Advances in salivary gland pathology.
AB  - This review summarizes the new findings on salivary gland pathology under the
      following categories: immunohistochemistry; molecular genetics; newly recognized
      tumour types; known tumour entities with new findings; and progression of
      salivary gland tumours. In the application of immunohistochemistry, CD117 can aid
      in highlighting the luminal cell component of various salivary gland tumours,
      whereas p63 or maspin can aid in highlighting the abluminal cell component. A
      high Ki67 index remains the most useful marker to predict adverse outcome in
      salivary gland carcinoma. Specific chromosomal translocations are recognized in
      pleomorphic adenoma (with translocation involving PLGA1 or HMGA2 gene) and
      mucoepidermoid carcinoma (with MECT1-MAML2 gene fusion). Newly recognized
      entities include: sclerosing polycystic adenosis (with recent molecular evidence
      supporting its neoplastic nature), sclerosing mucoepidermoid carcinoma with
      eosinophilia, keratocystoma, adenoma with additional stromal component
      (lymphadenoma, lipoadenoma and adenofibroma), cribriform adenocarcinoma of the
      tongue and signet ring adenocarcinoma of minor salivary gland. Known tumour
      entities with new findings include: salivary duct carcinoma (with newly
      recognized mucinous, micropapillary and sarcomatoid variants), intraductal
      carcinoma (with controversies in terminology), mucoepidermoid carcinoma (with
      newly proposed grading parameters and oncocytic variant), epithelial
      myoepithelial carcinoma (with newly recognized morphological variants), small
      cell carcinoma (with most cases being related to Merkel cell carcinoma),
      extranodal marginal zone B-cell lymphoma (with specific chromosomal
      translocation) and chronic sclerosing sialadenitis (being a component of IgG4
      related sclerosing disease). Progression of salivary gland tumours can take the
      form of malignant transformation of a benign tumour, progression from low-grade
      to high-grade carcinoma, dedifferentiation, or stromal invasion of an in situ
      carcinoma.

PMID- 17539915
TI  - Unfavourable prognostic significance of S100P expression in ovarian cancers.

PMID- 17539916
TI  - Localized gastric crystal-storing histiocytosis.

PMID- 17539917
TI  - COX-2 oxidative metabolite of endocannabinoid 2-AG enhances excitatory
      glutamatergic synaptic transmission and induces neurotoxicity.
AB  - Neuroinflammation has been implicated in the pathogenesis of neurodegenerative
      diseases. Cyclooxygenase-2 (COX-2), an inducible enzyme converting arachidonic
      acid (AA) to prostaglandins, is the key player in neuroinflammation. It has been
      long thought that the COX-2-mediated neuronal injury/degeneration is attributed
      to the increased production of AA-derived prostaglandins. Recent studies show
      that endogenous cannabinoid 2-arachidonoylglycerol (2-AG) is a natural substrate
      for COX-2, and it can be oxygenated by COX-2 to form prostaglandin glyceryl
      esters. In this study, we demonstrate that prostaglandin E(2) glyceryl ester
      (PGE(2)-G), a major COX-2 oxidative metabolite of 2-arachidonoylglycerol,
      enhanced hippocampal glutamatergic synaptic transmission indicated by the
      increased frequency of miniature excitatory post-synaptic currents, and induced
      neuronal injury/death revealed by the terminal transferase dUTP nick end labeling
      staining and caspase 3 activation. The actions of PGE(2)-G are not mediated via a
      cannabinoid receptor 1, but mediated through ERK, p38 mitogen-activated protein
      kinase, IP(3), and NF-kappaB signal transduction pathways. In addition, the
      PGE(2)-G-induced neurotoxicity is attenuated by blockade of the NMDA receptors.
      Our results suggest that the COX-2 oxidative metabolism of endocannabinoids is an
      important mechanism contributing to the inflammation-induced neurodegeneration.

PMID- 17539918
TI  - An in vitro model of aneurysmal subarachnoid hemorrhage: oxidation of
      unconjugated bilirubin by cytochrome oxidase.
AB  - Aneurysmal subarachnoid hemorrhage is a stroke subtype with high rates of
      mortality and morbidity. Cerebral vasospasm can lead to ischemic injury or death
      and is a common complication of aneurysmal subarachnoid hemorrhage, usually
      occurring 3-9 days afterwards. The cause of vasospasm is not known. Recently,
      there has been strong evidence that vasoactive oxidation products of bilirubin
      may be involved. Currently, the factors that lead to bilirubin oxidation are
      poorly characterized. In this study, we have designed an in vitro model of
      hemorrhagic stroke in order to investigate conditions that promote the oxidation
      of bilirubin to form vasoactive compounds. Using our model, we created a basic
      hematoma system of blood, CSF, and hemeoxygenase-1. We manipulated this system in
      various ways, incubated it and determined the concentration of vasoactive
      bilirubin oxidation products that resulted. Conditions where cytochrome oxidase
      was stimulated caused an increase bilirubin oxidation products (292.6 +/- 39.9
      micromol/L respectively, vs. 79.3 +/- 1.3 micromol/L for the basic reaction, p <
      0.05), which was attenuated by cyanide. Our data suggest that bilirubin oxidation
      products may be produced by oxidation(s) requiring an oxygen-utilizing enzyme
      like cytochrome oxidase.

PMID- 17539919
TI  - Influence of human tryptophan hydroxylase 2 N- and C-terminus on enzymatic
      activity and oligomerization.
AB  - Tryptophan hydroxylase (TPH) catalyses the first and rate limiting step in the
      biosynthesis of the neurotransmitter serotonin. There are two TPH isoenzymes in
      humans, encoded by two different genes: TPH1 and the recently described TPH2. We
      have expressed both human enzymes and various deletion mutants of TPH2 (DeltaN44,
      DeltaC17, DeltaC19, DeltaC51) in COS7 cells. TPH1 and 2 displayed different
      kinetic properties with a lower K(m) value of TPH1. Removal of 44 amino acids
      from the N-terminus of TPH2 resulted in a 3-4-fold increased V(max), which
      indicates a strong inhibitory function of this part on the enzymes activity. TPH1
      and 2 were able to form homooligomers and also heterooligomers with each other.
      The different deletion mutants (DeltaC17, DeltaC19 and DeltaC51), which lack the
      putative C-terminal leucine zipper tetramerization domain, existed as monomeric
      enzymes. While short deletions (DeltaC17 and DeltaC19) hardly changed V(max)
      values, the DeltaC51 mutant lost 99% of TPH activity. These data identify a
      region between the C-terminal oligomerization domain and the catalytic domain,
      which is indispensable for TPH2 activity.

PMID- 17539920
TI  - Potassium- and capsaicin-induced release of agmatine from spinal nerve terminals.
AB  - Agmatine (decarboxylated arginine) was originally identified in the CNS as an
      imidazoline receptor ligand. Further studies demonstrated that agmatine
      antagonizes NMDA receptors and inhibits nitric oxide synthase. Intrathecally
      administered agmatine inhibits opioid tolerance and hyperalgesia evoked by
      inflammation, nerve injury, and intrathecally administered NMDA. These actions
      suggest an anti-glutamatergic role for agmatine in the spinal cord. We have
      previously reported that radiolabeled agmatine is transported into spinal
      synaptosomes in an energy- and temperature-dependent manner. In the present
      study, we demonstrate that agmatine is releasable from purified spinal nerve
      terminals upon depolarization. When exposed to either elevated potassium or
      capsaicin, tritiated agmatine (but not its precursor L-arginine or its metabolite
      putrescine) is released in a calcium-dependent manner. Control experiments
      confirmed that the observed release was specific to depolarization and not due to
      permeabilization of or degradation of synaptosomes. That capsaicin-evoked
      stimulation results in agmatine release implicates the participation of primary
      afferent nerve terminals. Radiolabeled agmatine also accumulates in purified
      spinal synaptosomal vesicles in a temperature-dependent manner, suggesting that
      the source of releasable agmatine may be vesicular in origin. These results
      support the proposal that agmatine may serve as a spinal neuromodulator involved
      in pain processing.

PMID- 17539921
TI  - Effects of caffeine on anticipatory control processes: evidence from a cued task
      switch paradigm.
AB  - Effects of caffeine on task switching were studied using ERPs in a cued task
      switch paradigm. The need for advance preparation was manipulated by varying the
      number of task-set aspects that required switching. In a double-blind, within
      subjects experiment, caffeine reduced shift costs compared to placebo. ERPs
      revealed a negative deflection developing within the preparatory interval, which
      was larger for shift than for repeat trials. Caffeine increased this shift
      induced difference. Furthermore, shift costs increased as a function of the
      number of task-set features to be switched, but this pattern was not modulated by
      caffeine. The results suggest that caffeine improves task-switching performance
      by increasing general effects on task switching, related to task-nonspecific
      (rather than task-specific) anticipatory processes. Caffeine's actions may be
      mediated by dopaminergic changes in the striatum or anterior cingulate cortex.

PMID- 17539922
TI  - Delayed recovery of conjugate eye deviation and head version.

PMID- 17539924
TI  - Relapsing neuromyelitis optica responsive to glatiramer acetate treatment.

PMID- 17539925
TI  - Comments on published article by F. Deisenhammer et al.

PMID- 17539927
TI  - 16q-linked autosomal dominant cerebellar ataxia in a Korean family.

PMID- 17539928
TI  - PANDAS in siblings: a common risk?

PMID- 17539929
TI  - MRI scans of cervical cord provide evidence of anterior horn lesion in a patient
      with tick-borne encephalomyeloradiculitis.

PMID- 17539930
TI  - Comments on the report of the EFNS task force on IFN-beta antibodies in multiple
      sclerosis.

PMID- 17539931
TI  - Guidelines on use of anti-IFN-B antibody measurements in multiple sclerosis:
      report of an EFNS Task Force on IFN-B antibodies in multiple sclerosis.

PMID- 17539932
TI  - Acute stroke units are effective, also in eastern Europe.

PMID- 17539933
TI  - Resource allocation to brain research in Europe.

PMID- 17539934
TI  - Remission of progressive multifocal leukoencephalopathy and primary central
      nervous system lymphoma in an HIV-infected patient.
AB  - The coexistence of progressive multifocal leukoencephalopathy (PML) and primary
      central nervous system lymphoma (PCNSL) is a rare event, usually associated with
      a fatal outcome. We report the case of a human immunodeficiency virus (HIV)
      infected individual presenting with both PML and PCNSL who made a remarkable
      recovery after highly active anti retroviral therapy (HAART) and radiation
      therapy, and discuss diagnostic and therapeutic aspects of both conditions.

PMID- 17539935
TI  - Hospital-referred polyneuropathies--causes, prevalences, clinical- and
      neurophysiological findings.
AB  - The aim of this study was to evaluate the causes, prevalences, clinical
      manifestations of hospital-referred polyneuropathies, and evaluate
      neurophysiological findings in idiopathic polyneuropathy. From 2000 to 2005, 226
      patients with polyneuropathy were examined. Polyneuropathy was diagnosed when
      symptoms, clinical- and neurophysiological findings were compatible with
      affection of at least two peripheral nerves. They were classified in symptomatic
      and idiopathic polyneuropathy after investigation. Clinical manifestations were
      evaluated for diabetes- (DPN), inflammatory- (INPN), hereditary- (HPN) and
      idiopathic polyneuropathy (IDPN). Neurophysiological findings were investigated
      in IDPN. 72% had a symptomatic polyneuropathy. Most frequent causes were diabetes
      mellitus (18%), inflammation, (16%) and hereditary (14%). Most common prevalences
      per 100,000 were as follows: IDPN, 21; DPN, 13 and HPN, 11. Predominating
      clinical manifestations were: sensory and motor in INPN, HPN and IPN; sensory in
      DPN. Pain was more present in IDPN and DPN than in others. In IDPN axonal
      demyelinating affection was present in 20%. Symptomatic polyneuropathy was common
      and diabetes mellitus, inflammation and hereditary were frequent causes. In IDPN,
      DPN, HPN and INPN different clinical patterns were found. Additionally, in IDPN
      axonal demyelinating affection was more frequent than previously reported.

PMID- 17539936
TI  - Prevalence and cognitive performances of vascular cognitive impairment no
      dementia in Japan: the Osaki-Tajiri Project.
AB  - Prevalence, magnetic resonance imaging (MRI) findings, cognitive function and
      depression are four major aspects of vascular cognitive impairment no dementia
      (vascular CIND). We performed a community-based study to examine these using 497
      community-residents aged 65 years or older. Vascular CIND was defined as a
      clinical dementia rating (CDR) 0.5 with cerebrovascular disease. Several
      neuropsychological tests were performed, including MMSE, Geriatric Depression
      Scale (GDS), and Trail Making Test (TMT). Cerebrovascular disease and white
      matter lesions were visually assessed using MRI. Prevalence of vascular CIND,
      localization of cerebrovascular disease, and the relationships amongst MRI
      findings, white matter lesions, cognitive impairment and depression were
      analyzed. The prevalence of vascular CIND was 8.5% amongst the total population,
      corresponding to the rate being 37.2% amongst the CDR 0.5 participants. Compared
      with the CDR 0, the CDR 0.5 group had more subjects with strategic
      cerebrovascular disease in the thalamus, etc. No effects of cerebrovascular
      disease on MMSE and GDS scores were found, but the CDR 0.5/strategic
      cerebrovascular disease group showed impaired TMT-B scores. In the CDR 0 group,
      only anterior periventricular hyperintensity was associated with TMT-A score
      independent of cerebrovascular disease. A vascular CIND population was
      identified, and executive dysfunction in this population is probably based on an
      impaired fronto-subcortical circuit.

PMID- 17539937
TI  - Myasthenia gravis patients with ryanodine receptor antibodies have distinctive
      clinical features.
AB  - Myasthenia gravis (MG) is an autoimmune disease caused in 85% of the patients by
      acetylcholine receptor (AChR) antibodies. Non-AChR muscle antibodies, against
      titin and ryanodine receptor (RyR) are mainly found in sera of patients with
      thymoma or late-onset MG. The occurrence of RyR antibodies increases the risk for
      severe MG and should lead to active immunomodulating treatment already at MG
      onset. The aim in this study was to describe the association between symptoms at
      MG onset and antibody profile in 152 patients. Patients with RyR antibodies had
      the highest rate of bulbar, respiratory and neck involvement at MG onset. They
      also had the highest frequency of non-limb MG symptoms. Neck weakness occurred in
      40%. Respiratory difficulties at MG onset occurred in patients with titin
      antibodies, with and without RyR antibodies. Patients with RyR antibodies have a
      distinctive non-limb MG symptom profile, with bulbar, ocular, neck, and
      respiratory symptoms. These features, identified as early as at the first
      examination by a neurologist, characterize the RyR antibody positive subgroup at
      MG onset.

PMID- 17539938
TI  - Polymorphisms at codons 129 and 219 of the prion protein gene (PRNP) are not
      associated with sporadic Alzheimer's disease in the Korean population.
AB  - Polymorphisms of prion protein gene (PRNP) at codons 129 and 219 play an
      important role in the susceptibility to Creutzfeldt-Jakob disease (CJD).
      Alzheimer's disease (AD) and prion diseases, such as CJD, are both characterized
      by the accumulation of abnormally folded proteins in the brain. An association
      between sporadic AD and the PRNP polymorphism at codon 129 has been reported in
      several studies, but other studies have failed to confirm an association. To
      investigate whether PRNP polymorphisms are associated with an increased risk for
      developing sporadic AD in the Korean population, we compared the genotype,
      allele, and haplotype frequencies of PRNP polymorphisms in 271 sporadic AD
      patients with those in 236 healthy Koreans. Our study does not show a significant
      difference in PRNP genotype, allele, and haplotype frequency at codons 129 and
      219 between sporadic AD and normal controls. Analyses stratifying by age at
      disease onset, and gender also failed to reveal any association between these
      polymorphisms and sporadic AD. These results indicate that these PRNP
      polymorphisms have no direct influence on the susceptibility to sporadic AD in
      the Korean population.

PMID- 17539939
TI  - Reduction of optic nerve fiber layer thickness in CADASIL.
AB  - Our study aims to assess nerve fiber layer (NFL) thickness in patients affected
      by cerebral autosomal dominant arteriopathy with subcortical infarcts and
      leucoencephalopathy (CADASIL). Six CADASIL patients (mean age 42 +/- 16 years,
      best corrected visual acuity >20/20 with refractive error between +/-3 diopters,
      intraocular pressure <18 mmHg) were enrolled. They were compared with 16 age
      matched controls. In all subjects enrolled, NFL thickness was measured by optical
      coherence tomography (OCT). Three different measurements were taken in each
      quadrant (superior, inferior, nasal, and temporal) and averaged. The data from
      all quadrants (12 values averaged) were identified as NFL overall. In CADASIL
      eyes there was a reduction of NFL thickness in each quadrant and in the NFL
      overall evaluation compared with the values observed in control eyes. Our results
      suggest that in CADASIL patients there is a reduction of NFL thickness evaluated
      by OCT. This morphological abnormality could be ascribed to an impairment of the
      retinal vascular supply leading to a global neuroretinal involvement. These
      anatomical changes may precede the onset of the neurological clinical
      manifestations.

PMID- 17539940
TI  - Action and object naming in Parkinson's disease without dementia.
AB  - The present study aimed to assess the ability in objects and actions naming in
      Parkinson's disease (PD) patients. Further, we wished to assess the effect of a
      particular conceptual dimension, i.e. manipulability, on the naming of object and
      actions. Patients were recruited from the Department of Neurology, University of
      Brescia. Thirty-two were diagnosed as PD, according to published criteria, and 15
      healthy volunteers matched in age and education to patients' sample. All patients
      underwent a detailed clinical and neurological evaluation. The stimuli used in
      the action-object picture naming task were taken from the Center for Research in
      Language-International Picture Naming Project corpus. To assess the effect of
      manipulability (or the involvement of fine hand movements) the noun-verb stimuli
      were re-categorized into manipulable and non-manipulable items (i.e. objects
      which can or cannot be manipulated and actions which do or do not involve fine
      hand movements). Patients showed a deficit both in action and object naming,
      compared with controls. In addition, patients with PD but not controls were
      significantly more impaired in action than in object naming. The current study
      supports the view that action naming is affected in patients with PD, possibly
      reflecting the presence of prefrontal dysfunction.

PMID- 17539941
TI  - A comparative study of chronic inflammatory demyelinating polyradiculoneuropathy
      with and without diabetes mellitus.
AB  - Diabetes mellitus (DM) is occasionally associated with chronic inflammatory
      demyelinating polyradiculoneuropathy (CIDP) raising the question of coexistence
      or etiological link. The study compares, neurophysiological and outcome of CIDP
      patients with and without DM. Consecutive CIDP patients were subjected to
      detailed clinical evaluation, haematology, serum chemistry, vasculitis profile,
      paraproteins, myeloma screening and cerebrospinal fluid (CSF) examination.
      Electrodiagnostic (EDx) tests included motor and sensory conduction and F-wave
      studies. The patients were treated with oral prednisolone 1 mg/kg/day with or
      without azathioprine 1-2 mg/kg and followed up for 6 months. The clinical and EDx
      finding in CIDP with and without DM were compared. Thirty-five CIDP patients were
      included and nine had DM. CIDP with diabetes (CIDP-D) had higher frequency of
      autonomic dysfunction. In CIDP-D, motor (38.9% vs. 16.7%) and sensory (40.7% vs.
      14.1%) nerve conductions were more frequently unrecordable or had reduced
      compound muscle action potential (CMAP) amplitude. F-waves were also more
      frequently unrecordable in CIDP-D (28.8% vs. 12.8%) compared with idiopathic CIDP
      (I-CIDP). The degree of conduction block was more in I-CIDP. At 6-month follow
      up, I-CIDP patients improved better than CIDP-D. CIDP-D patients present with
      higher frequency of autonomic dysfunction, electrophysiological evidences of
      associated axonal loss and had a poorer outcome at 6 months compared with I-CIDP.

PMID- 17539942
TI  - Awareness of potential valvulopathy risk with pergolide and changes in clinical
      practice after label change: a survey among European neurologists.
AB  - In response to concern about the reported frequency of ergot-associated
      valvulopathy in patients with Parkinson's disease (PD), Eli Lilly and Company
      updated the Risk Minimization Program for pergolide, changing the Summary of
      Product Characteristics (SmPC) and distributing a Dear Doctor Letter (DDL)
      highlighting the new label changes. A survey was conducted subsequently to assess
      neurologists' awareness of the revised SmPC and their resulting changes in
      practice. A random sample of 20.3% of neurologists (n = 4056) from 12 eligible EU
      countries were invited to participate. Of the target population of 247
      neurologists who treated patients with PD, used pergolide in 2005, and were
      willing to participate, 244 (99%) responded. Overall awareness of the DDL and the
      SmPC changes was 94.2%. Over half (58.3%) of neurologists indicated that they
      prescribe pergolide exclusively as second-line treatment, although some (21.9%)
      used pergolide exclusively as first-line treatment. In response to the DDL, most
      neurologists perform echocardiograms before treatment (67.5%) and during
      treatment (76.7%), and over half (55%) avoid prescribing doses >5 mg/day.
      Overall, use of a DDL to communicate an SmPC change was effective in increasing
      the awareness of pergolide-associated valvulopathy and in modifying neurologists'
      clinical practice to minimize this risk.

PMID- 17539943
TI  - Antigen-specific oligoclonal bands in cerebrospinal fluid and serum from patients
      with anti-amphiphysin- and anti-CV2/CRMP5 associated paraneoplastic neurological
      syndromes.
AB  - Using isoelectric focusing and affinity blotting employing paraneoplastic
      recombinant antigens, we investigated cerebrospinal fluid (CSF) and sera from
      three patients with positive anti-CV2/CRMP5- and one patient with positive anti
      amphiphysin serology. CSF and sera were previously adjusted to total IgG
      concentrations of 20 mg/l. All patients suffered from paraneoplastic neurological
      syndromes (PNS) with predominant involvement of the central nervous system (CNS).
      Using affinity blot preloaded with paraneoplastic antigen, we detected in three
      of four patients more or stronger specific oligoclonal bands (OCB) in the CSF
      than in the corresponding serum, providing qualitative evidence of antigen
      specific intrathecal antibody synthesis. These results are in line with previous
      studies demonstrating specific OCB predominantly in CSF from patients with anti
      Hu-, anti-Yo- and anti-Ri-associated PNS, supporting the hypothesis of
      autoimmunity in the pathogenesis of PNS. One patient harboured extensive anti
      amphiphysin specific OCB, although OCB of total IgG could not be detected,
      indicating a higher sensitivity for detection of intrathecal antibody synthesis
      of the affinity blot preloaded with the paraneoplastic antigen, compared with
      investigation of total IgG OCB. These results could have implications concerning
      pathophysiological autoimmune aspects in other inflammatory diseases of CNS
      associated with total IgG OCB, provided that the target antigen is known.

PMID- 17539944
TI  - Paresthesia as a favorable predictor of migraine prophylaxis using topiramate.
AB  - Migraineurs treated with topiramate often experience adverse effects, such as
      paresthesia, fatigue, memory difficulty, or taste perversion. To investigate
      correlations between side effects and drug efficacy, we analyzed for these in 133
      migraineurs treated with topiramate (100 mg/day). A 4-week baseline screening
      phase preceded a 4-week titration period and a 20-week maintenance phase. A total
      of 118 patients were evaluated at 3 months and 89 patients at 6 months. Patients
      who developed paresthesia (n = 73) showed lower headache days than those who did
      not (n = 60) (P = 0.026 at 3 months, P = 0.002 at 6 months), and had a higher
      responder rate (3 months, 57.5% and 6 months, 65.8%) than those who did not
      develop paresthesia (3 months, 38.3% and 6 months, 41.7%). Moreover,
      retrospective analysis of patients that dropped out showed no survival bias
      between paresthesia and headache improvement. Other adverse effects were not
      found to correlate with drug efficacy. This study suggests that the development
      of paresthesia predicts a favorable response to topiramate in migraine
      prophylaxis.

PMID- 17539945
TI  - Clinical characteristics of carriers of a GAG deletion in the DYT1 gene amongst
      Polish patients with primary dystonia.
AB  - DYT1 primary torsion dystonia is an autosomal dominant disorder caused by
      deletion of a GAG triplet in exon 5 of the DYT1 gene. A significant proportion of
      individuals with early-onset generalized dystonia is believed to be DYT1 mutation
      carriers. We assessed the frequency of the GAG deletion in the DYT1 gene in a
      group of 61 Polish probands with clinical diagnosis of primary dystonia. The
      deletion was identified in four probands presenting with early-onset generalized
      disease (7%). Further studies in probands' families revealed two symptomatic and
      nine asymptomatic mutation carriers. We tested all mutation-positive individuals
      for the presence of some common polymorphisms within the DYT1 gene. Two of the 15
      mutation-positive individuals additionally carried polymorphisms in 3'-UTR of the
      gene. Early onset in a limb and progression toward a generalized form, but not
      family history of dystonia, are indicative of DYT1 dystonia in Polish dystonic
      individuals.

PMID- 17539946
TI  - Double-blind crossover trial of gabapentin in SPG4-linked hereditary spastic
      paraplegia.
AB  - Patients with hereditary spastic paraplegia (HSP) are often treated with
      antispastic drugs to relieve symptoms but documentation is lacking. In this
      study, gabapentin was tested in a double-blind crossover trial on a group of
      patients with HSP and linkage to the SPG4 locus. There was no difference between
      periods with gabapentin and placebo treatment in clinical assessment, self
      reported parameters or paired transcranial magnetic stimulation evaluation of
      motor cortical excitability.

PMID- 17539947
TI  - Resource allocation to brain research in Denmark: an example for other European
      countries.
AB  - This study represents a first attempt at estimating Danish resource allocation to
      brain research including both public and private spending. It appears that
      private spending is at a reasonable level because a highly developed Danish
      pharmaceutical industry invests significantly in this branch of science. However,
      public spending is at a low level compared with several other European countries
      with a similar economic status. As for other European countries the funding is
      very low compared with the USA. Dedicated national investigations of the resource
      allocation to different branches of biomedical research are warranted. Brain
      research should of course be an important part of such studies. The USA and the
      European Union have selected brain research as one of their priority areas within
      health-related research. The present figures indicate that this is highly
      justified and should be copied in Denmark and in all other European countries.

PMID- 17539948
TI  - Timing of stenting of symptomatic carotid stenosis is predictive of 30-day
      outcome.
AB  - For patients with symptomatic carotid stenosis, benefit from carotid artery
      stenting (CAS) highly depends on the 30-day stroke and death rates.
      Identification of predictors of unfavourable outcome would help guide the patient
      selection. We analysed the influence of clinical and angiographic factors on the
      30-day outcomes of 77 consecutive patients who underwent CAS for > or = 60%
      symptomatic carotid stenosis within 180 days of transient ischaemic attack or
      moderate stroke (modified Rankin Scale score < or = 3). The 30-day composite end
      point for stroke (7.8%) and death of any cause (1.3%) was 9.1%. Patients with
      complicated CAS were older than patients with uncomplicated CAS (mean age 75.1 +/
      8.2 vs. 65.9 +/- 9.5 years, P = 0.015) and underwent stenting significantly
      earlier after the qualifying event: median delay 1.5 weeks (range: 0.2-3.0) vs.
      3.2 weeks (range: 0.5-26), P = 0.004. In multivariate logistic regression
      analyses, age [odds ratio (OR) = 1.148; 95% confidence interval (CI): 1.011-1.304
      and P = 0.033] and delay of treatment < 2 weeks (OR = 22.399; 95% CI: 2.245
      223.445 and P = 0.008) remained the only variables significantly associated with
      30-day outcome. CAS carries a considerable risk in old patients and when
      performed early (< 2 weeks) after the qualifying event. Future reports should
      address the timing of CAS.

PMID- 17539949
TI  - What is the relationship among atherosclerosis markers, apolipoprotein E
      polymorphism and dementia?
AB  - Evidence suggests the important role of vascular factors both in vascular
      dementia (VaD) and Alzheimer disease (AD) pathogenesis. However, the relationship
      between apolipoprotein E (APOE) polymorphism and markers of atherosclerosis is
      still controversial. The aim of the study was to investigate the interplay
      between APOE polymorphisms and atherosclerosis in patients with AD and VaD. In
      this cross-sectional study, 101 demented (68 AD and 33 VaD) patients underwent
      APOE genotyping and neck vessel ultrasound to evaluate carotid artery disease
      [intima-media thickness (IMT) and plaques]. Patients with AD carrying epsilon4
      allele presented increased IMT values with respect to non-epsilon4 carriers and
      VaD patients, whereas no relation was found between APOE polymorphisms and the
      presence or grade of carotid plaques both in AD and VaD patients. The epsilon4
      APOE allele may promote intima-media thickening, interacting with other factors
      contributing to AD development.

PMID- 17539950
TI  - Cardioembolic stroke secondary to non-bacterial endocarditis in Wegener disease.
AB  - Wegener granulomatosis is a systemic vasculitis that mainly affects the upper and
      lower respiratory tract and the kidneys. The presence of an ischemic stroke in
      this disease is very rare. A 40-year-old man, smoker with cavitated lesions in
      both lungs, and inflammation in the nasal mucosa and vocal cords developed an
      ischemic stroke in the left middle cerebral artery, with the etiological study
      showing non-bacterial endocarditis. Non-bacterial endocarditis can appear in
      patients with Wegener granulomatosis, with this being the first case of this
      cardioembolism reported in this disease.

PMID- 17539951
TI  - Cladribine in aggressive forms of multiple sclerosis.
AB  - Cladribine (2-chlorodeoxyadenosine) is an immunosuppressant drug previously
      evaluated in multiple sclerosis (MS) with variable results. We report six
      patients with aggressive relapsing MS who despite a poor response to other
      therapies had a favourable clinical evolution after cladribine. Four women and
      two men with a rapid increase in the number and severity of relapses leading to
      increasing disability [mean Expanded Disability Status Scale (EDSS) 6.42,
      standard deviation +/- 0.58, mean relapse rate per year in the 2 years prior to
      study entry 2.67 +/- 0.75] were retrospectively evaluated. Brain magnetic
      resonance imaging (MRI) performed in five patients showed active disease with
      gadolinium-enhancing lesions. Cladribine was given at 0.07 mg/kg/day for five
      consecutive days once monthly with a total of 2- to 4-monthly courses. After 6
      months, mean EDSS decreased to 3.75 +/- 1.64 and MRIs showed a decrease or
      suppression in the number of gadolinium-enhancing lesions. After 1 year from
      first dose, cladribine dosage was repeated in four patients because of recurrence
      of relapses with subsequent similar positive clinical results. In the follow-up
      period (49.33 +/- 39.66 months), the mean relapse rate decreased to 0.71 +/- 0.55
      and no unexpected or serious adverse events were observed.

PMID- 17539952
TI  - Imaging of acetylcholine esterase activity in brainstem nuclei involved in
      regulation of sleep and wakefulness.
AB  - Positron emission tomography with 11C-N-methyl-4-piperidyl-acetate (MP4A) was
      applied in eight healthy volunteers and two patients with mild Alzheimer's
      disease (AD) to assess acetylcholine esterase (AChE) activity in magnetic
      resonance imaging-identified brainstem nuclei. Uptake ratios in lateral dorsal
      tegmental and pedunculopontine nuclei relative to cerebellum yielded reproducible
      values for the AChE activity in controls and reduced values in AD, more marked in
      a patient with complaints of disturbed sleep. Cortical AChE activity was related
      to the extent of cognitive impairment which was more severe in the AD patient
      without sleep disturbance. This preliminary observational study demonstrates the
      feasibility to image and assess AChE activity in small nuclei of the brain stem.
      This approach may be helpful to investigate the interaction of various nuclei in
      the complex network regulating sleep and wakefulness in representative patient
      groups with documented sleep disturbance.

PMID- 17539953
TI  - The use of gabapentin in chronic cluster headache patients refractory to first
      line therapy.
AB  - Chronic cluster headache (CCH) is a rare but challenging condition. About 20% of
      CCH patients get refractory to treatment. Gabapentin has recently been reported
      to be efficacious in the treatment of CCH. To test the potential of gabapentin as
      second-line drug, we prospectively studied the efficacy of gabapentin as add-on
      drug in eight patients suffering from CCH refractory to first-line treatment. Six
      of eight CCH patients responded to treatment. After the end of the study phase,
      the patients' clinical course was further followed up until January 2006. The
      longest period of being continuously pain-free under gabapentin treatment was 18
      months. In some individuals, increasing doses were needed with time. We conclude
      that gabapentin may be offered as treatment trial in patients refractory to first
      line treatment. However, patients may fail to respond to treatment and drug
      tolerance may occur with time.

PMID- 17539954
TI  - Anterior opercular syndrome in frontotemporal lobar degeneration with ubiquitin
      only immunoreactive neuronal changes.
AB  - This paper presents for the first time an anterior opercular syndrome in
      association with a gait disorder, dropped head syndrome, dysphagia, and
      sialorrhea in a neuropathologically proven case of frontotemporal lobar
      degeneration with ubiquitin inclusions.

PMID- 17539955
TI  - Efficacy of lisinopril in migraine prophylaxis--an open label study.
AB  - The ACE-inhibitor lisinopril has previously been shown to be effective in
      migraine prophylaxis at a daily dose of 20 mg. To test the effect of a low dose
      of lisinopril (5 mg daily) in migraine prevention, we performed an open label
      study in 21 migraineurs. The primary outcome measure was frequency of migraine
      attacks. Secondary efficacy measures were migraine hours, intake of acute
      migraine drugs, pain intensity and responder rate. Compared with baseline
      conditions, the attack frequency of migraine attacks was significantly reduced (P
      < 0.0005). The number of acute migraine drugs dropped significantly (P = 0.002).
      Three patients dropped out because of intolerable cough. Our study suggests that
      even low doses of lisinopril may be effective in migraine treatment. However, its
      use may be limited by intolerable side-effects.

PMID- 17539956
TI  - Carotidynia: a new case for an old controversy.
AB  - Whereas International Headache society (IHS) criteria of carotidynia were defined
      in 1988, its validity as a distinct nosological entity has recently been
      questioned, leading this entity to be removed from the second IHS classification
      in 2004. We report the case of a 30-year-old woman who developed a pain located
      at the left carotid bulb, associated with typical findings on ultrasonography and
      MRI. We discuss new criteria and denomination of this clinical entity.

PMID- 17539957
TI  - Association study of a functional variant in intron 8 of the dopamine transporter
      gene and migraine susceptibility.
AB  - Migraine is a common, genetically influenced neurovascular disorder. The dopamine
      transporter gene is a candidate for migraine association studies. This study
      tested a functionally linked variable number tandem repeat (VNTR) in intron 8 of
      the dopamine transporter gene (DAT(Int8)) in 550 migraine cases (401 with aura,
      149 without aura) and 550 non-migraine controls. Chi-squared analysis of the
      DAT(Int8) revealed that the allele and genotype frequency distributions for
      migraine cases (including subtype analysis) and controls were not different (P >
      0.1). These findings offer no evidence for an association of the DAT(Int8) with
      migraine with and without aura and therefore do not implicate the dopamine
      transporter gene as a modifier of migraine risk.

PMID- 17539958
TI  - Brain research has high returns but Europe is lagging behind.
AB  - We have shown that brain disorders cost Europe almost 400 billion euros annually,
      whereas the funding for brain research is only 1% of that amount. There is a
      growing understanding of the ability of research to improve prevention, treatment
      and rehabilitation of brain disease and thereby reduce the burden on the affected
      individuals and on society. New studies have shown that brain research is highly
      profitable, with conservatively measured annual returns of 50% or more. However,
      funding of brain research in Europe, particularly public funding, is lagging
      behind when compared with the US. We argue that increased public investment in
      brain research in Europe is critical and will most likely be highly cost
      effective to European society. If Europe wants to remain competitive in the field
      of brain research, public investments must be increased several fold over today's
      investment.

PMID- 17539960
TI  - Clinicopathological and molecular characteristics of gastric and colorectal
      carcinomas in the elderly.
AB  - The occurrence of malignant neoplasms increases with advancing age. Although
      aging and carcinogenesis are basically different processes, there are phenomena
      common to each such as accumulation of DNA damage and abnormal proteins. Gastric
      and colorectal carcinomas are representative tumors in which the prevalence and
      the number of patients increase significantly with age. Compared with gastric and
      colorectal cancers occurring in younger patients, those occurring in older
      patients have clinicopathological differences in tumor location, gender
      distribution, histological type, histological diversity, multiplicity, incidence
      of lymph node metastasis, and prognosis. In the elderly there are peculiar types
      of carcinoma such as medullary-type poorly differentiated colorectal
      adenocarcinoma and solid-type poorly differentiated gastric adenocarcinoma, both
      of which occur in older women. Methylation, apoptosis, and telomere dysfunction
      play important roles in the development of gastric and colorectal cancers in the
      elderly.

PMID- 17539961
TI  - Two distinct pathways of tumorigenesis of adenocarcinomas of the esophagogastric
      junction, related or unrelated to intestinal metaplasia.
AB  - It is still uncertain whether intestinal metaplasia (IM) of the esophagogastric
      junction (EGJ) plays a role in the development of adenocarcinoma of the
      esophagogastric junction (AEGJ). The purpose of the present study was to clarify
      the relationship between AEGJ and IM in Japanese patients. Forty-eight AEGJ, <3
      cm and centered within 1 cm of the EGJ, were investigated. The frequency of IM
      around AEGJ and the correlation between IM and clinicopathological features were
      examined. IM was present in the surrounding mucosa in 22 of 48 cases (46%), and
      was seen more frequently in older patients (P = 0.008). Lymph node metastasis was
      observed only in cases in which the tumors were not associated with IM (P =
      0.017). The gastric phenotype was seen almost exclusively in the group without
      IM, while the intestinal phenotype was predominant in the group with IM (P =
      0.003). The present study found a lower incidence of associated IM than Western
      studies, and there were significant differences in clinicopathological features
      between AEGJ with and without IM. It is suggested that AEGJ may develop via two
      distinct pathways in Japanese patients: IM-related and IM-unrelated.

PMID- 17539962
TI  - Characteristics of vulvar squamous cell carcinoma in Japanese women.
AB  - Although the presence of racial differences in vulvar squamous cell carcinomas
      has been suggested, fully analyzed data concerning such tumors in Japanese women
      have not been reported. A total of 21 vulvar squamous cell carcinomas of Japanese
      women who lived in north-east Japan, were studied with respect to histological
      subtype, HPV, p53 and p16(INK4a). The majority of tumors consisted of
      keratinizing and non-keratinizing types (16/21, 76%), all of which were negative
      for HPV. The remaining five tumors of basaloid, warty or verrucous types were
      positive for HPV. HPV-negative tumors showed a trend of greater accumulation of
      gene abnormalities, including p53 gene mutation, than HPV-positive ones.
      p16(INK4a) overexpression was shown to not always be a marker for vulvar squamous
      cell carcinoma in Japanese women with activated high-risk HPV.

PMID- 17539963
TI  - Association of p16INK4A hypermethylation with hepatitis B virus X protein
      expression in the early stage of HBV-associated hepatocarcinogenesis.
AB  - The aim of the present study was to explore the relationship between methylation
      status of the p16(INK4A) promoter and some HBV-related factors, and the role of
      these factors in p16(INK4A) hypermethylation and hepatocellular carcinoma (HCC)
      progression. Twenty-three cases of surgically resected HBV-associated HCC and 25
      fine-needle aspiration biopsy cases of chronic hepatitis B (CHB) were studied.
      The methylation status of the p16(INK4A) promoter was determined by methylation
      specific polymerase chain reaction (PCR). Two-step immunohistochemical staining
      showed the expression of viral antigens in situ. Tissue HBV-DNA levels were
      determined by fluorescence quantitative real-time PCR. PCR and the direct
      sequencing method were used for mutation analysis. In peritumoral tissues (P =
      0.025) and CHB samples (P = 0.029), the expression of hepatitis B virus X protein
      (HBx) was higher in methylated groups of p16(INK4A) promoter than in unmethylated
      groups. Other HBV factors including hepatitis B surface antigen and hepatitis B
      core antigen, tissue HBV-DNA levels and HBV x gene mutations had no relation to
      the methylation status of p16(INK4A) promoter. The data indicate that p16(INK4A)
      promoter hypermethylation correlated closely with higher HBx expression in the
      precancerous lesions, suggesting that HBx may play an important role in the early
      stage of HBV-associated hepatocarcinogenesis via induction of hypermethylation of
      p16(INK4A) promoter.

PMID- 17539964
TI  - Factor XIIIa-positive dermal dendritic cells in keloids and hypertrophic and
      mature scars.
AB  - Keloids and hypertrophic scars have several common features. Both are reddish,
      firm, slightly protruding lesions that consist of proliferative fibroblastic
      cells and collagenous tissues. The aim of the present study was to evaluate the
      contribution of factor XIIIa (FXIIIa)-positive dermal dendritic cells to
      formation of keloids and hypertrophic scars. The numbers of FXIIIa-positive cells
      were counted in the keloid, hypertrophic scar and mature scar, each of which was
      divided into fibrocollagenous area and superficial dermal area overlying the
      nodular lesion. The features of the FXIIIa-positive cells were examined using
      immunohistochemical and immunoelectron microscopic techniques. More FXIIIa
      positive cells were present in the overlying dermal area than in the
      fibrocollagenous area, commonly in three types of dermal lesion. The number of
      FXIIIa-positive dendritic cells was significantly greater in the overlying dermal
      area of keloids than in the corresponding area of hypertrophic or mature scar.
      Immunoelectron microscopic examination showed that the immunoreactivity for
      FXIIIa was seen mainly at the periphery of the cytoplasm of dermal dendritic
      cells. These results suggest that FXIIIa-positive dendritic cells in the
      overlying dermal area play active roles in formation of keloids and may
      contribute to dermal-epidermal interactions in keloids.

PMID- 17539965
TI  - Immunohistochemical and immunochemical study of amyloid in liver affected by
      systemic Alambda amyloidosis with antibodies against three different regions of
      immunoglobulin lambda light chain.
AB  - The purpose of the present paper was to investigate the heterogeneous nature of
      amyloid deposits in the liver, by immunohistochemical and immunochemical
      examination of liver samples from cases of immunoglobulin lambda light chain
      amyloidosis (Alambda amyloidosis) with antibodies generated against the peptides
      corresponding to the three different regions of the lambda light chain. Amyloid
      deposits in the hepatic artery tended to react better with anti-lambda(118-134)
      than with anti-lambda(159-175). Amyloid deposits in the space of Disse tended to
      react weakly or partially with anti-lambda(118-134) but well with anti-lambda(159
      175). Amyloid deposits in the portal vein reacted relatively well with both
      antibodies. By western blotting of water-extracted amyloid in which amyloid
      deposits were not stained with anti-lambda(118-134) immunohistochemically, the
      three antibodies detected 27 kDa bands consistent with the full-length Ig lambda
      chain and some smaller bands. These findings indicate that amyloid deposits may
      not be homogeneous in the liver of AL amyloidosis, and that molecular
      heterogeneity of amyloid fibril protein or a difference in the mode of deposition
      results in the histopathological heterogeneity of AL amyloid deposits even within
      a single patient.

PMID- 17539966
TI  - Activation of the lectin complement pathway in post-streptococcal acute
      glomerulonephritis.
AB  - The aim of the present study was to elucidate the correlation between complement
      pathways and clinicopathological findings in post-streptococcal acute
      glomerulonephritis (PSAGN). Immunohistological staining was performed on renal
      specimens obtained from 18 patients with PSAGN and 20 controls, using antibodies
      against IgG, IgA, IgM, C1q, C3c, C4, fibrinogen, factor B, C4-binding protein (C4
      bp), C5b-9, CD59, mannose-binding lectin (MBL) and MBL-associated serine protease
      1 (MASP-1). Controls showed no deposition of any antibody. In seven patients,
      glomerular deposits of C3c, C4, factor B, C4-bp, C5b-9, CD59, MBL and MASP-1 were
      found. In the remaining 11 patients, glomerular deposits of neither C4 nor
      MBL/MASP-1 were found, and glomerular deposits of C3c, factor B, C5b-9 and CD59
      were evident. C4-bp was detected in seven of these 11 patients. Glomerular
      deposits of fibrinogen were detected in five of seven patients with MBL/MASP-1
      deposits and in only two of 11 patients without MBL/MASP-1 deposits. Hematuria
      was prolonged in three of seven patients with MBL/MASP-1 deposits through follow
      up, whereas urinalysis was normal in all patients without MBL/MASP-1 deposits.
      However, the histological indicators were not different between the two groups.
      To the authors' knowledge this is the first report to show that complement
      activation through both the alternative and lectin pathways is evident in some
      patients with PSAGN. Complement activation is promoted in situ in the glomerulus.

PMID- 17539967
TI  - Distribution of nestin and other stem cell-related molecules in developing and
      diseased human spinal cord.
AB  - In mammalian spinal cords, no neurogenesis has been observed after initial
      development. However developed mammalian spinal cords seemingly contain neural
      stem cells (NSC), which can give rise to neurons and glial cells when they are
      placed in appropriate environments. The purpose of the present paper was to
      investigate the developing, developed, and diseased human spinal cord to see
      which cell types have an immunophenotype similar to NSC. In 12 specimens from
      preterm neonates and term infants up to 14 months old, nestin was expressed in
      cells that extended fibrous processes and were located around the midline in the
      ependymal layer. In all the preterm neonates, Musashi-1 and glial fibrillary
      acidic protein (GFAP) were also expressed in this subpopulation, whereas Lewis X
      was detected in a less restricted subpopulation. Nestin expression by these cells
      was not detected in most adult spinal cords, but was observed in three spinal
      cords from 13 amyotrophic lateral sclerosis patients and eight of 14 spinal cords
      involved by the tumor. The present observations suggest that during gestation a
      subpopulation of cells in the ependymal layer remains undifferentiated as
      potential NSC/neural progenitor cells, and becomes unidentifiable in early
      infancy. These cells, however, appear in response to disease conditions,
      especially tumor involvement.

PMID- 17539968
TI  - Quantitative image analysis in adipose tissue using an automated image analysis
      system: differential effects of peroxisome proliferator-activated receptor-alpha
      and -gamma agonist on white and brown adipose tissue morphology in AKR obese and
      db/db diabetic mice.
AB  - Morphometric analysis of adipocytes is widely used to demonstrate the effects of
      antiobesity drugs or anti-diabetic drugs on adipose tissues. However, adipocyte
      morphometry has been quantitatively performed by manual object extraction using
      conventional image analysis systems. The authors have developed an automated
      quantitative image analysis method for adipose tissues using an innovative object
      based quantitative image analysis system (eCognition). Using this system, it has
      been shown quantitatively that morphological features of adipose tissues of mice
      treated with peroxisome proliferator-activated receptor (PPAR) agonists differ
      dramatically depending on the type of PPAR agonist. Marked alteration of
      morphological characteristics of brown adipose tissue (BAT) treated with
      GI259578A, a PPAR-alpha agonist, was observed in AKR/J (AKR) obese mice.
      Furthermore, there was a 22.8% decrease in the mean size of adipocytes in white
      adipose tissue (WAT) compared with vehicle. In diabetic db/db mice, the PPAR
      gamma agonist GW347845X decreased the mean size of adipocytes in WAT by 15.4%
      compared with vehicle. In contrast to changes in WAT, GW347845X increased the
      mean size of adipocytes in BAT greatly by 96.1% compared with vehicle. These
      findings suggest that GI259578A may activate fatty acid oxidation in BAT and that
      GW347845X may cause adipocyte differentiation in WAT and enhancement of lipid
      storage in BAT.

PMID- 17539969
TI  - Histopathological bone marrow changes after reduced-intensity hematopoietic stem
      cell transplantation for follicular lymphoma involving bone marrow.
AB  - Allogeneic stem cell transplantation (allo-SCT) is used as curative therapy for
      malignant lymphoma, and reduced-intensity hematopoietic stem cell transplantation
      (RIST) is sometimes performed to avoid the toxicity and mortality associated with
      myeloablative allo-SCT. RIST is generally preferred for elderly patients with
      malignant lymphoma. A 62-year-old woman with follicular lymphoma (FL) involving
      bone marrow (BM) suffered relapse after autologous SCT. RIST was performed; cells
      were from an unrelated, fully human leukocyte antigen-matched donor. To study the
      hematopoietic reconstitution, BM biopsy specimens that were obtained at different
      times after RIST, were evaluated. Engraftment of donor cells was observed on days
      19 and 48 after RIST, and residual FL in BM had completely disappeared by day 73
      after RIST. This is the first report to document histological BM regeneration
      after RIST and disappearance of FL involving the BM.

PMID- 17539970
TI  - Pulmonary tumor thrombotic microangiopathy resulting from metastatic signet ring
      cell carcinoma of the stomach.
AB  - Pulmonary tumor thrombotic microangiopathy is an unusual malignancy-related
      respiratory complication characterized by multiple microthrombi and intimal
      myofibroblast proliferation. Its clinical manifestation is subacute respiratory
      failure with pulmonary hypertension. Herein is reported a case of pulmonary tumor
      thrombotic microangiopathy associated with gastric signet ring cell carcinoma. A
      51-year-old woman with gastric cancer died of subacute respiratory failure.
      Autopsy showed gastric signet ring cell carcinoma with diffuse metastasis of
      pulmonary lymphatics and pleurae; every organ examined lacked a space-occupying
      tumor mass. Histologically, proliferated intimal myofibroblasts obliterated most
      of the pulmonary vascular lumen, and a few stenosed vascular lumina contained
      cancer cells. In addition, pulmonary vasculature associated with intimal
      proliferation contained microthrombi. Most cancer cells in the stomach and
      pulmonary lymphatics were typical signet ring cells, whereas those in vascular
      lesions were cells of poorly differentiated adenocarcinoma without mucous
      production. Consistent with a previous report, the latter expressed vascular
      endothelial growth factor (VEGF) and tissue factor (TF). The proliferated intimal
      myofibroblasts also expressed type 2A serotonin receptor (5-HT(2A)). These
      findings suggest that local expression of VEGF, TF, and 5-HT(2A) may be linked to
      the pathogenesis of this unusual pulmonary complication.

PMID- 17539971
TI  - Exposure to a high total dosage of glucocorticoids produces non-alcoholic
      steatohepatits.

PMID- 17539972
TI  - Differential gene expression of aldolase C (ALDOC) and hypoxic adaptation in
      chickens.
AB  - Two sequence variants of the aldolase C (ALDOC) gene were discovered based on
      comparison of the sequences from an altiplano chicken breed (Tibetan chicken) and
      two lowland breeds (White Leghorn and ShouGuang). Gel-shift results indicated
      that one of these variants, L25375:c.310-258G>A, was able to bind hypoxia-induced
      factor-l (HIF1A), therefore, functioning as a hypoxia response element (HRE). The
      combined activity of the HRE and HIF1A could increase under the influence of a
      hypoxic stimulus. Hypoxia leads to increased death rates of chicken embryos,
      while the L25375:c.310-258G>A described herein is prevalent in healthy embryos
      grown under hypoxic conditions. Fluorescence quantitative real-time PCR results
      revealed that HIF1A upregulated the transcript level of the glycolytic enzyme
      ALDOC in the brain and skeletal muscle of animals subjected to hypoxia. Thus, a
      large amount of ATP is produced by increased glycolysis, allowing the organism to
      meet energy metabolism demands. As such, we believe this sequence variant is an
      adaptation to external anoxic environment.

PMID- 17539973
TI  - Analysis of mtDNA sequences shows Japanese native chickens have multiple origins.
AB  - In this study, we analysed the mitochondrial DNA D-loop region of Japanese native
      chickens to clarify their phylogenetic relationships, possible maternal origin
      and routes of introduction into Japan. Seven haplogroups (Types A-G) were
      identified. Types A-C were observed in Jidori, Shokoku and related breeds.
      However, Type C was absent in Shokoku, which was introduced from China, while
      most Indonesian native chickens were included in the Type C haplogroup. Types D-G
      were observed in Shamo and related breeds. Type E had a close genetic
      relationship with Chinese native chickens. Our results indicate that some breeds
      were not introduced into Japan as suggested in conventional literature, based on
      low nucleotide diversity of certain chicken breeds. Sequences originating from
      China and Korea could be clearly distinguished from those originating from
      Southeast Asia. In each group, domestic chickens were divided into the Jidori
      Shokoku and Shamo groups. These results indicate that Chinese and Korean chickens
      were derived from Southeast Asia. Following the domestication of red junglefowl,
      a non-game type chicken was developed, and it spread to China. A game type
      chicken was developed in each area. Both non-game and game chickens formed the
      foundation of Japanese native chickens.

PMID- 17539974
TI  - Evaluation of Compass as a comparative mapping tool for ESTs using horse
      radiation hybrid maps.
AB  - Loci for 9322 equine expressed sequence tags (ESTs) were predicted using the
      Comparative Mapping by Annotation and Sequence Similarity (Compass) strategy in
      order to evaluate the programme's ability to make accurate locus predictions in
      species with comparative gene maps. Using human genome sequence information from
      Build 35 (May 2004) and published marker information from the radiation hybrid
      (RH) maps for equine chromosomes (ECA) 17 and X, 162 ESTs were predicted to
      locations on ECA17 and 328 ESTs to locations on ECAX by selection of the 'top
      blast hit'. The locations of 30 ESTs were assessed experimentally by RH mapping
      analysis to evaluate the accuracy of the Compass predictions. The data revealed
      that 53% (16 of 30) of the ESTs predicted on ECA17 and ECAX mapped to those
      chromosomes. Analysis of the results suggested the need to identify expressed
      orthologous sequences in order to generate more accurate predictions for ESTs.
      Locus predictions were reassessed with three modifications to the Compass
      strategy's orthologue selection parameters. Selection of the 'top gene hit'
      improved accuracy to 72% (21 of 29), while selection of the 'top expressed gene
      hit' improved accuracy to 86% (24 of 28). Using the default Compass parameters
      with the UniGene database improved prediction accuracy to 96% (22 of 23);
      however, this level of accuracy came with a substantial decrease in the total
      number of predictions. When used with optimized prediction parameters, the
      Compass strategy can be a practical in silico map location prediction tool for
      large EST sample sets from unsequenced animal genomes.

PMID- 17539975
TI  - FISH mapping of 57 BAC clones reveals strong conservation of synteny between
      Galliformes and Anseriformes.
AB  - Karyotypes of chicken (Gallus gallus domesticus; 2n = 78) and mallard duck (Anas
      platyrhynchos; 2n = 80) share the typical organization of avian karyotypes
      including a few macrochromosome pairs, numerous indistinguishable
      microchromosomes, and Z and W sex chromosomes. Previous banding studies revealed
      great similarities between chickens and ducks, but it was not possible to use
      comparative banding for the microchromosomes. In order to establish precise
      chromosome correspondences between these two species, particularly for
      microchromosomes, we hybridized 57 BAC clones previously assigned to the chicken
      genome to duck metaphase spreads. Although most of the clones showed similar
      localizations, we found a few intrachromosomal rearrangements of the
      macrochromosomes and an additional microchromosome pair in ducks. BAC clones
      specific for chicken microchromosomes were localized to separate duck
      microchromosomes and clones mapping to the same chicken microchromosome
      hybridized to the same duck microchromosome, demonstrating a high conservation of
      synteny. These results demonstrate that the evolution of karyotypes in avian
      species is the result of fusion and/or fission processes and not translocations.

PMID- 17539976
TI  - Review article: the role of surgery in gastro-oesophageal reflux disease.
AB  - BACKGROUND: Rates for laparoscopic fundoplication are declining in the United
      States and there is no consensus on the indications for referral to surgery in
      gastro-oesophageal reflux disease. AIM: To highlight recent studies on the
      outcomes of laparoscopic fundoplication in adults that cast doubt on the
      traditional indications for surgery in reflux disease. RESULTS: Patients who are
      well maintained on medical therapy have more to lose with surgical intervention
      than to gain, and should not be offered surgery. Likewise, the notion that
      surgery prevents oesophageal cancer is a hypothesis that is not supported by
      current evidence, therefore surgical intervention should not be offered to these
      patients. The only clear-cut candidates for surgery include: patients with
      anatomic abnormalities such as a large hiatus hernia, or those with persistent
      regurgitation that causes troublesome symptoms despite medical therapy; and
      carefully selected patients with extra-oesophageal disorders who have symptoms of
      reflux disease such as heartburn and regurgitation, an incomplete response to
      medical therapy and persistent plus demonstrable reflux on pH or impedance
      testing that is associated with their symptoms. Patients should be aware of the
      high likelihood of needing continued acid inhibitory therapy following surgery
      and the possibility of side-effects. CONCLUSION: Only a few carefully selected
      patients should undergo fundoplication for reflux disease.

PMID- 17539977
TI  - Review article: the diagnosis and management of Crohn's disease in populations
      with high-risk rates for tuberculosis.
AB  - BACKGROUND: Distinguishing Crohn's disease from intestinal tuberculosis in
      endemic areas is challenging as both conditions have overlapping clinical,
      radiological, endoscopic and histological characteristics. Furthermore, high
      rates of latent tuberculosis confer a considerable risk of reactivation once
      therapy for established Crohn's disease is started. AIM: To review current
      strategies in differentiating these two conditions, and in managing Crohn's
      disease, in populations with high rates of tuberculosis. METHODS: Literature
      review and clinical experience. RESULTS: While various clinical, radiological,
      endoscopic and histological parameters may aid in differentiating Crohn's disease
      from intestinal tuberculosis, these remain imperfect and as treatment options
      differ misdiagnosis has grave consequences. We propose a diagnostic algorithm,
      based on currently available evidence and experience, to aid in this dilemma. We
      also discuss approaches to the management of Crohn's disease, including agents
      targeting tumour necrosis factor-alpha, in patients at risk of developing
      tuberculosis. CONCLUSIONS: A diagnosis of Crohn's disease in individuals at risk
      for tuberculosis should only be made after careful interpretation of clinical
      signs, abdominal imaging and systematic endoscopic and histological assessment.
      Newer techniques for the diagnosis of latent tuberculosis still need to be
      validated in this environment, and guidelines on the treatment of latent
      tuberculosis in this setting require clarification.

PMID- 17539978
TI  - Systematic review: the potential influence of mesalazine formulation on
      maintenance of remission in Crohn's disease.
AB  - AIM: To evaluate the effectiveness of pH 6-/pH 7-dependent and controlled-release
      mesalazines in maintaining medically and surgically induced Crohn's disease
      remission. METHODS: A systematic search identified 13 randomized controlled
      trials (RCTs). The rate of symptomatic relapse (Crohn's disease activity index
      >150, or an increase in baseline by at least 60-100 points) was extracted from
      each randomized controlled trial. Pooled odds ratios (OR), the number needed to
      treat (NNT), and percentage therapeutic benefit (absolute risk reduction) were
      calculated. RESULTS: Treatment with pH 7-dependent mesalazine significantly
      reduced the risk of relapse in patients with either surgically [OR 0.28; 95%
      confidence interval (CI) 0.12-0.65; P = 0.0032] or medically induced remission
      (OR 0.38; 95% CI 0.17-0.85; P = 0.0113). However, treatment with controlled
      release mesalazine and pH 6-dependent mesalazine failed to show any significant
      advantage over placebo. The NNT to maintain surgically or medically induced
      remission was lowest for pH 7-dependent mesalazine (NNT = 4 and 5, respectively;
      NNT = 15 and 16 for controlled-release mesalazine and NNT = 11 and 23 for pH 6
      dependent mesalazine). Therapeutic benefit was highest for pH 7-dependent
      mesalazine (surgical = 30.6%, medical = 22.8%). This compared with 6.9%
      (surgical) and 6.4% (medical) for controlled-release mesalazine, and 9.8% and
      4.4%, respectively, for pH 6-dependent mesalazine. CONCLUSION: Further trials of
      pH 7-dependent mesalazine formulations are warranted in the maintenance of
      remission in Crohn's disease.

PMID- 17539979
TI  - Risk of acute liver injury associated with the use of drugs: a multicentre
      population survey.
AB  - BACKGROUND: Acute liver injury of uncertain aetiology is often drug related and
      quantitative information about the associated risk is scarce. AIM: To estimate
      the risk of acute liver injury associated with the use of drugs. METHODS: In a
      population survey study, 126 cases of acute liver injury were prospectively
      assembled from January 1993 to December 1999, in patients over 15 years of age,
      in 12 hospitals in Barcelona (Spain). We estimated the relative risk for each
      drug as the ratio between the incidence of acute liver injury among the exposed
      population to the drug and the incidence of acute liver injury among those not
      exposed to it. Drug consumption data were used to estimate the exposed
      population. RESULTS: Isoniazid, pyrazinamide, rifampicin, amoxicillin with
      clavulanic acid, erythromicin, chlorpromazine, nimesulide, and ticlopidine
      presented the highest risk (point relative risk > 25). Amoxicillin,
      metoclopramide, captopril and enalapril, furosemide, hydrochlorothiazide,
      fluoxetine, paroxetine, diazepam, alprazolam, lorazepam, metamizole, low-dose
      acetylsalicylic acid and salbutamol showed the lowest risk (point relative risk <
      5). CONCLUSIONS: This study provides a risk estimation of serious liver disease
      for various drugs that will be useful in its diagnosis and management, and when
      comparing with the drug therapeutic benefit in each indication. Some observed
      associations would be worth specific studies.

PMID- 17539980
TI  - The impact of eosinophilia and hepatic necrosis on prognosis in patients with
      drug-induced liver injury.
AB  - BACKGROUND: Drug-induced liver injury may be immunologically mediated or
      metabolically induced. Peripheral eosinophilia and liver eosinophilia in
      suspected drug-induced liver injury generally supports the role of drug
      aetiology. AIM: To assess the importance of eosinophilia and hepatic necrosis on
      outcome in patients with suspected drug-induced liver injury. METHODS: We
      performed search of MEDLINE for case reports on drug-induced liver injury
      associated with: amoxicillin/clavulanic acid, carbamazepine, diclofenac,
      disulfiram, erythromycin, flucloxacillin, halothane, isoniazid, phenytoin,
      sulindac and trimethoprim/sulfametoxazol. RESULTS: A total of 570 case reports
      were retrieved. Mortality/transplantation occurred in 112 (20%). Eosinophilia in
      peripheral blood was reported in 34% of cases, eosinophilia in liver biopsies in
      40%, and hepatic necrosis in 41%. Bilirubin levels were lower in patients with
      peripheral eosinophilia [5.5 x upper limit of normal (interquartile range 2.9-10)
      vs. 7.7 (4-17); P = 0.02] and patients with liver eosinophilia [5 x upper limit
      of normal (2.7-10) vs. 10 (5.4-20); P = 0.003] as compared with those without
      eosinophilia. Eosinophilia in peripheral blood and eosinophilia in liver biopsies
      were more common in patients who recovered (37% vs. 15.6%; P = 0.0001 and 48% vs.
      18.8%; P < 0.0001, respectively). Hepatic necrosis was present in 24% in the
      survivors vs. 84% in non-survivors (P < 0.0001). CONCLUSIONS: In drug-induced
      liver injury, a favourable outcome was related to the occurrence of eosinophilia,
      whereas hepatic necrosis was associated with a poor prognosis.

PMID- 17539981
TI  - Decreasing prevalence combined with increasing eradication of Helicobacter pylori
      infection in the United States has not resulted in fewer hospital admissions for
      peptic ulcer disease-related complications.
AB  - BACKGROUND: Helicobacter pylori infection is a major cause of peptic ulcer
      disease, but the prevalence of this infection has been decreasing steadily.
      Additionally, eradication of H. pylori decreases ulcer recurrence and prevents
      ulcer complications such as bleeding. AIM: To examine whether the decreased
      prevalence of H. pylori and increased use of eradication regimens have affected
      the prevalence of peptic ulcer disease-related hospitalizations. METHODS: We
      chose to study a period between 1996 and 2005. The number of gastric and duodenal
      ulcers as primary or secondary hospital discharge diagnoses per year for the 10
      year span was collected from five large US hospitals. Collected data were
      analysed using Spearman correlation. RESULTS: No statistically significant trend
      was observed in the number of gastric or duodenal ulcers listed as primary or
      secondary discharge diagnoses at any of the five healthcare centres. CONCLUSIONS:
      Despite a decreasing prevalence of H. pylori and the increasing use of successful
      H. pylori eradication regimens, the prevalence of peptic ulcer disease and its
      complications has not changed. In the US other aetiologies, including non
      steroidal anti-inflammatory drugs, may be playing a larger role than once
      thought.

PMID- 17539982
TI  - Primary antibiotic resistance in Helicobacter pylori strains isolated in northern
      and central Italy.
AB  - BACKGROUND: Helicobacter pylori resistance to antibiotics is increasing
      worldwide, and it reduces the efficacy of therapy. AIM: To assess current primary
      antibiotic resistance in H. pylori strains isolated in Italy. METHODS: Between
      June 2004 and June 2006, H. pylori strains were isolated consecutively in the two
      participating centres (Bologna, northern Italy; Rome, central Italy) from
      patients never previously treated for the infection. Isolated strains were tested
      for primary clarithromycin, metronidazole and levofloxacin resistance using as
      break point the minimal inhibitory concentration >/=1, >/=8 and >/=1 mg/L for the
      three antibiotics, respectively. RESULTS: Overall, 255 H. pylori strains were
      evaluated. The resistance rate was 16.9% for clarithromycin, 29.4% for
      metronidazole and 19.1% for levofloxacin. Clarithromycin resistance was
      significantly higher in non-ulcer dyspepsia than in peptic ulcer patients (19.1%
      vs. 0%, P = 0.02), metronidazole resistance was higher in foreign than Italian
      patients (50% vs. 22.9%, P = 0.0004) and levofloxacin resistance was higher in
      old than younger patients (28.4% vs. 14.4%, P = 0.048). Levofloxacin resistance
      was also more frequent in those strains with either clarithromycin or
      metronidazole resistance. CONCLUSION: A very high rate of primary resistance
      towards the tested antibiotics was detected in our study.

PMID- 17539983
TI  - Age at onset of inflammatory bowel disease and the risk of surgery for non
      neoplastic bowel disease.
AB  - BACKGROUND: There is conflicting data regarding the response to medical and
      surgical therapy for inflammatory bowel disease with respect to age at disease
      onset. AIM: To determine if the age at onset of Crohn's disease and ulcerative
      colitis is a risk factor for surgery for non-neoplastic bowel disease. METHODS:
      This was a case-control study of patients evaluated between 1998 and 2001. Cases
      had undergone an initial operation for bowel disease. Controls were matched 1:1
      for gender, disease subtype, date of first visit (+/-2 years), time from
      diagnosis prior to first visit (+/-3 years) and duration of follow-up.
      Association with age, disease extent, smoking history, medication use and co
      morbidities vs. case/control status was assessed using multiple variable
      conditional logistic regression to estimate the odds ratio (OR) and 95%
      confidence intervals (CI) for undergoing surgery. RESULTS: Among 132 Crohn's
      patients, older patients had lower odds for surgery (OR per 5 years, 0.86; 95%
      CI: 0.75-0.98). The rate of surgery for non-neoplastic bowel disease was not
      significantly associated with disease distribution, co-morbidities or cigarette
      smoking. Among 234 ulcerative colitis patients, the rate of surgery was unrelated
      to age, disease extent, co-morbidities or cigarette smoking, CONCLUSIONS: For
      Crohn's disease, but not ulcerative colitis, the risk of surgery for non
      neoplastic bowel disease decreases with increasing age at diagnosis, irrespective
      of disease distribution and history of cigarette smoking.

PMID- 17539984
TI  - Mesalazine downregulates c-Myc in human colon cancer cells. A key to its
      chemopreventive action?
AB  - BACKGROUND: Dysplasia and malignant transformation of colonocytes in ulcerative
      colitis are associated with overexpression of c-Myc and genes regulating cell
      survival. 5-Aminosalicylates such as mesalazine may reduce the development of
      colorectal cancer in ulcerative colitis, but the mechanisms of its
      chemopreventive action are not clear. AIMS: To examine whether mesalazine affects
      the expression of c-Myc in human colon cancer cell lines. METHODS: Human colon
      cancer cells were treated with vehicle or mesalazine (4 mm or 40 mm). We
      examined: (i) mRNA expression by gene array, (ii) protein expression by Western
      blotting and immunohistochemistry and (iii) apoptosis by Annexin V labelling.
      RESULTS: Mesalazine significantly reduced expression of c-Myc mRNA and protein.
      CONCLUSIONS: Mesalazine downregulates gene and protein expression of c-Myc. The
      apoptotic and growth inhibitory effects of mesalazine are dose-dependent.
      Expression of c-Myc is significantly reduced by mesalazine 40 mm.

PMID- 17539985
TI  - The gastro-oesophageal reflux disease impact scale: a patient management tool for
      primary care.
AB  - BACKGROUND: Symptoms of gastro-oesophageal reflux disease have a substantial
      impact on patients' everyday lives. AIM: To develop and test a short
      questionnaire to aid patient-doctor communication. METHODS: The Gastro
      oesophageal Reflux Disease Impact Scale was developed from a systematic
      literature review, focus groups of patients and primary care physicians, and
      patient cognitive interviews. A psychometric validation study was conducted based
      on two consultations in new (n = 100) or chronic (n = 105) gastro-oesophageal
      reflux disease patients. RESULTS: The Gastro-oesophageal Reflux Disease Impact
      Scale demonstrated internal consistency (Cronbach's alpha ranged from 0.68 to
      0.82), reproducibility (intraclass correlation coefficient in stable patients
      ranged from 0.61 to 0.72) and construct validity (Spearman correlations with
      Quality of Life in Reflux and Dyspepsia instrument and Reflux Disease
      Questionnaire: 0.5-0.8 in both patient groups). Effect sizes in new and chronic
      gastro-oesophageal reflux disease patients ranged from 0.9 to 1.5 and 0.32 to
      0.42, respectively. Doctors reported altering their treatment decision based on
      information provided by the Gastro-oesophageal Reflux Disease Impact Scale in 35%
      of patients, and 77% of doctors found it to be useful. CONCLUSIONS: The Gastro
      oesophageal Reflux Disease Impact Scale demonstrated good psychometric properties
      in newly diagnosed gastro-oesophageal reflux disease patients and those already
      receiving treatment. This simple communication tool is a useful aid for managing
      primary care patients with gastro-oesophageal reflux disease.

PMID- 17539986
TI  - A clinical trial comparing pantoprazole and esomeprazole to explore the concept
      of achieving 'complete remission' in gastro-oesophageal reflux disease.
AB  - BACKGROUND AND AIM: The outcome of gastro-oesophageal reflux disease treatment is
      traditionally assessed by measuring endoscopically confirmed healing and symptom
      relief separately. Both terms together, indicating complete remission, are
      intuitively a more realistic clinical endpoint but are assessed less often. AIM:
      To explore this concept, we formally compared the efficacy of the proton pump
      inhibitors (PPIs) pantoprazole and esomeprazole using rates of complete remission
      judged against rates of healing and symptom relief separately. METHODS: Five
      hundred and eighty-two patients with erosive gastro-oesophageal reflux disease
      were randomized to treatment for 4, 8, or 12 weeks with either pantoprazole or
      esomeprazole 40 mg daily. Symptom relief was assessed with the validated
      ReQuesttrade mark-GI subscale. RESULTS: Approximately 75% of patients were free
      of symptoms or had no oesophageal lesions after 4 weeks' treatment, rising to
      about 93% and 96%, respectively, at 12 weeks. Complete remission rates were,
      however, lower at these time points; approximately 60% and about 90%,
      respectively. Both PPIs had similar efficacy. CONCLUSIONS: Endoscopically
      confirmed healing and symptom relief assessed separately over-estimated the
      benefits of both drugs. In contrast, complete remission indicates that patients
      may be treated inadequately when given the standard 4- to 8-week treatment. We
      suggest that complete remission is a more reliable and clinically relevant
      endpoint of treatment.

PMID- 17539989
TI  - Is long-term interferon monotherapy welcome news for older patients with chronic
      hepatitis C genotype 1?

PMID- 17539987
TI  - Oral mucosa of coeliac disease patients produces antiendomysial and
      antitransglutaminase antibodies: the diagnostic usefulness of an in vitro culture
      system.
AB  - BACKGROUND: Antiendomysial (EmA) and antitransglutaminase (anti-tTG) antibodies
      are the most specific indirect marker of coeliac disease (CD). It is not known
      whether the oral mucosa of patients with CD is able to produce these antibodies
      or not. AIMS: To evaluate the ability of the oral mucosa of patients with CD to
      produce antibodies in an in vitro culture system. PATIENTS AND METHODS: Twenty
      eight patients with new diagnosis of CD (15 adults and 13 children) and 14 adult
      subjects with other diseases (controls) were studied. All underwent oral mucosa
      biopsy and subsequent EmA and anti-tTG assays on the mucosa culture medium.
      RESULTS: Sensitivity and specificity of EmA and anti-tTG assayed in the oral
      mucosa culture medium for CD diagnosis were 54% and 100% and 57% and 100%,
      respectively. The CD clinical presentation, such as the presence of oral mucosa
      lesions, did not influence the results of the EmA and anti-tTG assays in the oral
      mucosa culture medium. There was an association between positivity of antibodies
      and greater severity of the oral mucosa lymphocyte infiltration. CONCLUSION: This
      study demonstrates that the oral mucosa contributes to EmA and anti-tTG
      production in untreated patients with CD.

PMID- 17539990
TI  - Efficacy of low dose long-term interferon monotherapy in aged patients with
      chronic hepatitis C genotype 1 and its relation to alpha-fetoprotein: A pilot
      study.
AB  - AIM: The objective of this study was to examine the efficacy and safety of low
      dose long-term interferon (IFN) therapy in aged patients with chronic hepatitis C
      genotype 1. METHODS: The IFN therapy was performed in Shin-Kokura Hospital on 44
      patients aged 60 or older with chronic hepatitis C. All patients had high viral
      loads of genotype 1. Three million units of natural IFN-alpha was administered
      intramuscularly or intrasubcutaneously, three times a week for three years. A
      control group of 44 subjects not treated with IFN, matched for age, gender and
      hepatic histology, was formed. RESULTS: Two of the 44 patients showed a sustained
      virological response. Alanine aminotransferase was below the upper limit of
      normal in 59% (23/39) of the patients and alpha-fetoprotein was less than 40
      ng/mL in 97% (38/39) on the completion of treatment. Sustained biochemical
      response was observed in 53% (19/36) of the patients. In the liver cirrhosis
      group, serum albumin values and platelet counts increased in 38% (6/16) and 33%
      (6/18) of patients, respectively. Hepatocellular carcinoma (HCC) appeared in
      three patients by 13 months after the start of treatment, but no cases were
      reported thereafter. The cumulative non-carcinogenesis rate of HCC in the liver
      cirrhosis group was significantly higher in the IFN treatment group compared to
      the control group (log-rank test, P = 0.046). CONCLUSION: Low dose long-term
      interferon monotherapy to prevent carcinogenesis of HCC was considered useful in
      aged patients for whom peg-interferon and ribavirin combination therapy is
      difficult.

PMID- 17539991
TI  - The rate of hepatitis B and C virus infections and the importance of HBV
      vaccination in children with acute lymphoblastic leukemia.
AB  - AIM: The aim of the study was to evaluate the rate of hepatitis B and C virus
      infection and emphasize the importance of hepatitis B virus (HBV) vaccination in
      leukemic children. METHODS: One hundred and sixty children who were treated for
      acute lymphoblastic leukemia (ALL) at Hacettepe University Faculty of Medicine,
      Pediatric Hematology Unit were included in the study. They were 71 (44.4%) girls
      and 89 (55.6%) boys with a mean age of 6.45 +/- 3.87 years. RESULTS: Of these 160
      children, 22 (13.8%) were anti-HBs-positive and 138 (86.2%) were anti-HBs
      negative at the diagnosis of ALL. Among the 138 anti-HBs-negative children, 67
      (41.9%) were vaccinated for HBV during maintenance chemotherapy, and 71 (44.3%)
      could not be vaccinated. Two (2.9%) vaccinated and 22 (30.9%) unvaccinated
      children developed HBV infection during the follow-up period (P < 0.001). Among
      160 children treated for ALL, 24 (15.0%) had HBV, three (1.9%) had hepatitis C
      virus (HCV) infections, and 29 (18.1%) had toxic hepatitis. The majority of
      patients with HBV or HCV infections had high risk (HR) protocol, whereas most of
      the patients with toxic hepatitis had low risk (LR) protocol, especially St Jude
      Total XIII LR protocol. CONCLUSION: Viral hepatitis and toxic hepatitis were
      observed more commonly in the HR and LR group, respectively, of ALL patients.
      This could be explained by intensive chemotherapy and more heavy blood product
      administration in the HR group and the chemotherapeutic agents of methotrexate
      and 6-mercaptopurine, basic drugs used in the LR group. In respect to protection
      from these complications, periodical liver function tests, serological tests for
      HBV and HCV, and vaccination for HBV should be performed for all children with
      ALL.

PMID- 17539992
TI  - Lamivudine treatment-related morphological changes of esophageal varices in
      patients with liver cirrhosis.
AB  - AIM: Many studies have reported the therapeutic effects of lamivudine on
      cirrhotic patients with hepatitis B; however, no study has investigated the
      morphological changes of esophageal varices after lamivudine treatment. METHOD:
      The morphological changes of esophageal varices in patients with cirrhosis were
      retrospectively compared between 12 patients treated with lamivudine and six
      historical untreated patients. RESULTS: In the treated group, the HBV DNA and
      hyaluronic acid (HA) levels in the serum were significantly lower than those in
      the untreated group (P = 0.013 and P = 0.009, respectively) at the end of follow
      up, with a significant improvement in the Child-Pugh-Turcotte score (P = 0.022).
      In the treated group, the disappearance or reduction of esophageal varices was
      observed in six (50%) of the 12 patients. In three (25%) of the 12 patients,
      esophageal varices worsened. In the remaining three patients (25%), there were no
      changes in esophageal varices. In the untreated group, all patients showed the
      worsening of esophageal varices during the follow-up period, with a significant
      difference between this group and the treated group (P = 0.009). The serum HA
      level decreased in the nine treated patients without worsening of esophageal
      varices. However, in the three patients with worsening, the HA level
      significantly increased. CONCLUSION: Lamivudine treatment for patients with
      cirrhosis improves not only liver function but also esophageal varices.

PMID- 17539993
TI  - The effect of supplementation with branched-chain amino acids in patients with
      liver cirrhosis.
AB  - AIM: We investigated the effect of supplementation with branched-chain amino
      acids (BCAA) in patients with liver cirrhosis on the change of energy metabolism
      as well as glucose tolerance. METHODS: Thirty liver cirrhosis patients underwent
      nutrient supervision by a dietician for one week. They were then prescribed oral
      supplementation with three packs of a BCAA nutrient (Livact 4.15 g/pack;
      Ajinomoto Pharma, Tokyo, Japan), taken three times a day: after breakfast, dinner
      and before sleep. The change in energy metabolism and glucose tolerance was
      examined using an indirect calorimeter and 75 g oral glucose tolerance test (75 g
      OGTT). RESULTS: Non-protein respiratory quotient (npRQ) as well as branched-chain
      amino acid/tyrosine ratio (BTR) showed significant improvement, especially in
      patients with a creatinine height index (CHI) greater than 80. There was also a
      significant correlation between npRQ after one week of BCAA supplementation and
      the CHI. The patients with CHI greater than 80 and those with borderline pattern
      assessed by 75 g OGTT showed significant improvement in impaired glucose
      tolerance. CONCLUSION: Liver cirrhosis patients with CHI greater than 80 are the
      first candidates for BCAA supplementation. These patients showed improvement not
      only in energy metabolism and BTR, but also glucose tolerance.

PMID- 17539994
TI  - Diabetes mellitus increases the risk of hepatocarcinogenesis in patients with
      alcoholic cirrhosis: A preliminary report.
AB  - AIM: Diabetes mellitus (DM) has been reported to increase the risk of
      hepatocellular carcinogenesis in chronic liver diseases. This study aims to
      elucidate whether DM is an independent risk factor for the appearance of
      hepatocellular carcinoma (HCC) in patients with alcoholic cirrhosis. METHODS:
      Forty-seven patients with alcoholic cirrhosis were retrospectively observed for a
      median of 6.8 years. The patients showed a history of heavy alcohol intake of 500
      kg or more until the diagnosis of cirrhosis, and no patients had hepatitis B
      surface antigen, hepatitis B virus DNA measured by nested polymerase chain
      reaction, or antihepatitis C virus. RESULTS: During the observation period, HCC
      developed in nine patients (19.1%). Cumulative appearance rates of HCC were
      10.5%, 23.8% and 33.3% at the end of the fifth, 10th and 15th years,
      respectively. When they were divided into two groups according to the association
      of diabetes, carcinogenesis rates in patients with (n = 11) and without (n = 36)
      DM, cumulative carcinogenesis rates were 32.7% and 3.2% at the end of fifth year,
      32.7% and 20.2% at the tenth year, and 66.3% and 20.2% at the 15th year,
      respectively. Crude carcinogenesis rate in the patient with DM was significantly
      higher than that of patients without DM (P = 0.0034). Multivariate analysis
      disclosed a higher age (hazard ratio 28.1, P = 0.007), and association of DM
      (hazard ratio 21.7, P = 0.006) significantly affected future carcinogenesis rate.
      CONCLUSION: DM seemed to be an independent risk factor for hepatocarcinogenesis
      in the cohort study of patients with alcoholic cirrhosis.

PMID- 17539995
TI  - Inhibition of nuclear factor-kappa B induces inflammatory cell migration and
      exacerbates severe liver injury in hepatitis B virus transgenic mice.
AB  - AIM: Nuclear factor-kappa B (NF-kappaB) has a central role in co-ordinating the
      expression of a wide variety of genes that control the immune response and it is
      also recognized as an antiapoptotic transcription factor. In this study, we
      focused on the role of the NF-kappaB signaling pathway in liver injury induced in
      hepatitis B virus (HBV) transgenic mice. METHODS: A fulminant hepatitis model was
      created in mice by the adoptive transfer of antigen-specific cytotoxic T
      lymphocytes (CTLs) into HBV transgenic mice. We used an adenovirus expressing a
      mutant form of the IkappaB super-repressor (Ad5IkappaB), an NF-kappaB inhibitor,
      to inhibit the NF-kappaB signaling pathway. RESULTS: We observed that
      pretreatment with Ad5IkappaB increased the migration of inflammatory cells into
      the liver 6-24 h after a single intravenous injection of antigen-specific CTLs,
      in comparison to pretreatment with a control adenovirus. We also demonstrated
      that the presence of the NF-kappaB inhibitor exacerbated severe liver injury and
      hepatocellular apoptosis 24 h after the injection of the antigen-specific CTLs.
      CONCLUSION: These results suggest that the inhibition of NF-kappaB activity
      induces severe fulminant hepatitis in HBV transgenic mice.

PMID- 17539996
TI  - In vivo transfection of C/EBP-alpha gene could ameliorate CCL(4)-induced hepatic
      fibrosis in mice.
AB  - AIM: Hepatic stellate cells (HSCs) play a key role in liver fibrosis.
      CCAAT/enhancer-binding proteins-alpha (C/EBP-alpha) can inhibit HSCs activation
      in vitro, as described in our previous study. However, little is known about the
      in vivo effect of C/EBP-alpha gene in hepatic fibrosis. METHODS: Male BALB/c mice
      were injected by hydrodynamic protocol with pIRES2-EGFP-C/EBPalpha expression
      vector from the first to the fourth week (early intervention) or from the ninth
      to the 12th week (late intervention) after CCl(4) injection, respectively.
      Successful transfection of vector and the expression of C/EBP-alpha were
      confirmed with the appearance of green fluorescence in liver cells,
      immunohistochemical staining and the western blot. RESULTS: High expression of
      C/EBP-alpha gene in liver cells, especially in non-parenchymal cells, could
      reduce the content of collagens by 82.5% and 72.3% (Sirius red staining + image
      analysis) and the content of hydroxyproline by 56.3% and 51.6%, respectively, in
      the early and late intervention experiments. CONCLUSION: It is evident that
      exogenous C/EBP-alpha gene has an early and late intervention role in mice liver
      fibrosis.

PMID- 17539997
TI  - Cirrhosis and endotoxin decrease urea synthesis in rats.
AB  - AIM: In patients with cirrhosis, endotoxemia is frequent and the vitally
      important capacity for urea synthesis is impaired. The patients' mortality of
      infection is markedly increased, which could be related to adverse metabolic
      effects of endotoxins. The effects of endotoxins on in vivo urea synthesis and on
      urea cycle genes during cirrhosis are unknown. METHODS: We examined the effects
      of a low dose of 0.5 mg/kg ip lipopolysaccharide (LPS) on the basal urea nitrogen
      synthesis rate (UNSR), the capacity of urea nitrogen synthesis (CUNS), liver
      tissue mRNA levels of urea cycle enzyme genes, and on the metabolic liver
      function measured by the galactose elimination capacity (GEC) in rats with
      cirrhosis induced by bile duct ligation and in control animals. RESULTS: LPS and
      cirrhosis + LPS decreased UNSR by 40% (P < 0.05). Cirrhosis and LPS each tended
      to decrease CUNS and cirrhosis + LPS decreased CUNS by 40% (P < 0.05). Cirrhosis
      and LPS each decreased the mRNA level of the gene for the flux-generating urea
      cycle enzyme carbamoyl phosphate synthetase (CPS) and the mRNA for the rate
      limiting urea cycle enzyme arginine succinate synthetase (ASS) (P < 0.05).
      Cirrhosis + LPS left the mRNA level of CPS unchanged and decreased that of ASS (P
      < 0.05). The GEC did not differ among the study groups. CONCLUSION: Endotoxemia
      in rats with experimental cirrhosis markedly impaired the ability of the animals'
      livers to synthesize urea, suggesting a pathophysiological mechanism underlying
      the severe consequences of endotoxemia in human cirrhosis.

PMID- 17539998
TI  - Bezafibrate induces multidrug-resistance P-Glycoprotein 3 expression in cultured
      human hepatocytes and humanized livers of chimeric mice.
AB  - AIM AND METHODS: A decreased function of multidrug-resistance 3 P-glycoprotein
      (MDR3), limiting the rate of biliary phospholipid secretion, predisposes
      individuals to cholestasis and/or cholangitis. Fibrates induce the expression of
      mdr2 (homolog of human MDR3) in rodents. To investigate the effects of
      bezafibrate (BF) on the expression levels of MDR3 in cultured human hepatocytes
      and human livers, the amount of protein and subcellular localization of MDR3 was
      assessed in HepG2 cells treated with BF and humanized livers of BF-treated
      chimeric mice. RESULTS: In HepG2 cells, while treatment with BF did not increase
      the protein levels of MDR3, the treatment caused a redistribution of MDR3 in the
      bile canaliculi. In humanized livers of chimeric mice, oral administration of BF
      induced a large increase in the protein amount of MDR3 and its redistribution in
      the bile canaliculi. Moreover, the modulatory effects of BF on key factors
      involved in hepatic cholesterol and bile acid metabolism in human subjects were
      traced in the humanized livers of BF-treated chimeric mice. CONCLUSION: BF causes
      an induction of MDR3 expression in human livers. This provides a rationale for
      the beneficial role of BF in improving cholestasis and/or cholangitis associated
      with defective MDR3 expression and function in various types of cholestatic
      hepatobiliary diseases.

PMID- 17539999
TI  - Alpha-fetoprotein-specific transfer factors downregulate alpha-fetoprotein
      expression and specifically induce apoptosis in Bel7402 alpha-fetoprotein
      positive hepatocarcinoma cells.
AB  - AIM: To investigate the mechanisms of AFP-specific transfer factors (AFP-TF) in
      induced Bel7402 cells apoptosis. Further, we investigate the interaction between
      AFP-TF and AFP in the apoptosis. METHODS: Bel7402 and HepG2 AFP-positive
      hepatocarcinoma cell lines, SK-Hep-1 AFP-negative hepatocarcinoma cell line and
      Changliver normal liver cell line are used. Cell viability is evaluated by MTT
      assay and apoptosis is measured by Hoechst33342 staining and TUNEL assay. FACS is
      used to analyze the cell cycle. AFP expression is examined by RT-PCR, Western
      blotting and immunocytochemistry. The interaction between AFP-TF and AFP in the
      apoptosis is investigated by addition of AFP in cultures or AFP transfection in
      Bel7402 cells prior to AFP-TF treatment. Mitochondrial membrane potential
      (DeltaPsi(m)) and intracellular Ca2+ concentration are respectively measured by
      Rhodamine123 and Fluo-3 AM Ester. Western blotting detects the involvement of
      several apoptosis-related proteins. Finally, caspase-3 and Caspase-9 activity are
      respectively examined. RESULTS: AFP-TF can induce apoptosis in Bel7402 and HepG2
      AFP-positive hepatocarcinoma cells, but not SK-Hep-1 and Changliver cells. AFP
      mRNA level changes little in apoptotic Bel7402 cells; while AFP expression is
      downregulated and uniformly dispersed throughout the whole cell. Addition of
      exogenous AFP or overexpression of intracellular AFP can reduce such apoptotic
      effect. Besides, apoptotic Bel7402 cells show a disruption of DeltaPsi(m), an
      immediate elevation of Ca2+ concentration, a prominently decreased ratio of bcl-2
      to bax, a release of cytochrome c from mitochondria to cytosol, and ultimately an
      activation of caspase-9 and caspase-3. CONCLUSION: AFP-TF induced Bel7402 cells
      apoptosis is mitochondrial-dependent and is mediated by the interaction of AFP-TF
      with intracellular AFP.

PMID- 17540000
TI  - Associated benign liver tumors in idiopathic granulomatous hepatitis: A case
      report.
AB  - We report a unique association of ruptured hepatocellular adenoma, focal nodular
      hyperplasia and granulomatous hepatitis in a young woman taking oral
      contraceptives. Diffuse granulomatous hepatitis was found in the liver
      parenchyma, which was associated with a large granulomatous mass of the left lobe
      and loco-regional granulomatous lymphadenitis. We cannot give a full explanation
      of the situation, which represented a challenge in the diagnosis and in the
      treatment of this patient.

PMID- 17540001
TI  - Spontaneous ruptured primary hepatic angiosarcoma coincident with Schistosoma
      Japonica liver fibrosis.
AB  - AIM: We report herein a case of spontaneous ruptured primary hepatic angiosarcoma
      coincident with Schistosoma Japonica liver fibrosis and review the correlative
      literature. METHODS: The resected specimen was examined by histopathological and
      immunohistochemical evaluation. RESULTS: The final diagnosis was spontaneous
      ruptured primary hepatic angiosarcoma coincident with Schistosoma Japonica liver
      fibrosis Conclusion: Considering the nature of primary hepatic angiosarcoma, in
      particular the ruptured hepatic angiosarcoma, it is obviously desirable to avoid
      any unnecessary delay or definitive surgical treatment. It is presumed that
      angiosarcoma in the liver has a possible association with S. japonicum and the
      deposition of ovae in liver.

PMID- 17540002
TI  - Passive-active immunoprophylaxis for all infants born from HBeAG-negative chronic
      HBV-infected mothers: Is it a cost-effective strategy?

PMID- 17540003
TI  - Acidic extracellular pH increases calcium influx-triggered phospholipase D
      activity along with acidic sphingomyelinase activation to induce matrix
      metalloproteinase-9 expression in mouse metastatic melanoma.
AB  - Acidic extracellular pH is a common feature of tumor tissues. We have reported
      that culturing cells at acidic pH (5.4-6.5) induced matrix metalloproteinase-9
      expression through phospholipase D, extracellular signal regulated kinase 1/2 and
      p38 mitogen-activated protein kinases and nuclear factor-kappaB. Here, we show
      that acidic extracellular pH signaling involves both pathways of phospholipase D
      triggered by Ca2+ influx and acidic sphingomyelinase in mouse B16 melanoma cells.
      We found that BAPTA-AM [1,2-bis(2-aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid
      tetrakis (acetoxymethyl) ester], a chelator of intracellular free calcium, and
      the voltage dependent Ca2+ channel blockers, mibefradil (for T-type) and
      nimodipine (for L-type), dose-dependently inhibited acidic extracellular pH
      induced matrix metalloproteinase-9 expression. Intracellular free calcium
      concentration ([Ca2+]i) was transiently elevated by acidic extracellular pH, and
      this [Ca2+]i elevation was repressed by EGTA and the voltage dependent Ca2+
      channel blockers but not by phospholipase C inhibitor, suggesting that acidic
      extracellular pH increased [Ca2+]i through voltage dependent Ca2+ channel. In
      contrast, SR33557, an L-type voltage dependent Ca2+ channel blocker and acidic
      sphingomyelinase inhibitor, attenuated matrix metalloproteinase-9 induction but
      did not affect calcium influx. We found that acidic sphingomyelinase activity was
      induced by acidic extracellular pH and that the specific acidic sphingomyelinase
      inhibitors (perhexiline and desipramine) and siRNA targeting aSMase/smpd1 could
      inhibit acidic extracellular pH-induced matrix metalloproteinase-9 expression.
      BAPTA-AM reduced acidic extracellular pH-induced phospholipase D but not acidic
      sphingomyelinase acitivity. The acidic sphingomyelinase inhibitors did not affect
      the phosphorylation of extracellular signal regulated kinase 1/2 and p38, but
      they suppressed nuclear factor-kappaB activity. These data suggest that the
      calcium influx-triggered phospholipase D and acidic sphingomyelinase pathways of
      acidic extracellular pH induced matrix metalloproteinase-9 expression, at least
      in part, through nuclear factor-kappaB activation.

PMID- 17540004
TI  - The autophagic response to nutrient deprivation in the hl-1 cardiac myocyte is
      modulated by Bcl-2 and sarco/endoplasmic reticulum calcium stores.
AB  - Macroautophagy is a vital process in the cardiac myocyte: it plays a protective
      role in the response to ischemic injury, and chronic perturbation is causative in
      heart disease. Recent findings evidence a link between the apoptotic and
      autophagic pathways through the interaction of the antiapoptotic proteins Bcl-2
      and Bcl-XL with Beclin 1. However, the nature of the interaction, either in
      promoting or blocking autophagy, remains unclear. Here, using a highly sensitive,
      macroautophagy-specific flux assay allowing for the distinction between enhanced
      autophagosome production and suppressed autophagosome degradation, we
      investigated the control of Beclin 1 and Bcl-2 on nutrient deprivation-activated
      macroautophagy. We found that in HL-1 cardiac myocytes the relationship between
      Beclin 1 and Bcl-2 is subtle: Beclin 1 mutant lacking the Bcl-2-binding domain
      significantly reduced autophagic activity, indicating that Beclin 1-mediated
      autophagy required an interaction with Bcl-2. Overexpression of Bcl-2 had no
      effect on the autophagic response to nutrient deprivation; however, targeting Bcl
      2 to the sarco/endoplasmic reticulum (S/ER) significantly suppressed autophagy.
      The suppressive effect of S/ER-targeted Bcl-2 was in part due to the depletion of
      S/ER calcium stores. Intracellular scavenging of calcium by BAPTA-AM
      significantly blocked autophagy, and thapsigargin, an inhibitor of
      sarco/endoplasmic reticulum calcium ATPase, reduced autophagic activity by
      approximately 50%. In cells expressing Bcl-2-ER, thapsigargin maximally reduced
      autophagic flux. Thus, our results demonstrate that Bcl-2 negatively regulated
      the autophagic response at the level of S/ER calcium content rather than via
      direct interaction with Beclin 1. Moreover, we identify calcium homeostasis as an
      essential component of the autophagic response to nutrient deprivation.

PMID- 17540006
TI  - Chemotherapy for recurrent, metastatic, or persistent cervical cancer: a
      systematic review.
AB  - To determine the front-line chemotherapeutic options for women with recurrent,
      metastatic, or persistent cervical cancer. The Medline, Embase, and Cochrane
      Library databases were searched for randomized controlled trials (RCTs) comparing
      chemotherapy regimens for patients with recurrent, metastatic, or persistent
      cervical cancer. Studies were included if response rate, survival, toxicity, or
      quality of life data were reported. Fifteen RCTs were identified. The proportion
      of patients with prior chemoradiotherapy ranged from 0% to 57%. Four of the 15
      RCTs detected significant improvements in overall response with combination
      cisplatin-based chemotherapy when compared with single-agent cisplatin. One of
      the 15 RCTs reported a significant median survival advantage with topotecan and
      cisplatin when compared with single-agent cisplatin (9.4 vs 6.5 months, P =
      0.017); 57% of patients in this trial had previous chemoradiotherapy. Significant
      increases in grade 3 and 4 adverse events, especially severe hematologic
      toxicities, were detected among patients treated with that combination of
      chemotherapy. Thus, we conclude that cisplatin and topotecan should be discussed
      as a reasonable treatment option for appropriate patients who may wish to
      maximize the response and survival benefits associated with combination
      chemotherapy. Patients should understand that prior chemoradiotherapy with
      cisplatin may moderate the benefits observed, and that the relative benefits in
      response and survival outcomes come at the expense of increased toxicity. The
      improvement in median survival of 2.9 months represents a novel survival benefit
      in this difficult-to-treat patient population. Further randomized trials are
      needed to inform the role of single-agent or combination chemotherapy regimens,
      particularly in patients with prior chemoradiotherapy.

PMID- 17540007
TI  - Agonist selective modulation of tyrosine hydroxylase expression by cannabinoid
      ligands in a murine neuroblastoma cell line.
AB  - Functional interactions between catecholamines and cannabinoid transmission
      systems could explain the influence of Delta(9)-tetrahydrocannabinol on several
      central activities. Hence, the presence of cannabinoid CB(1) receptors in
      tyrosine hydroxylase (TH) containing cells has been suggested, providing clue for
      a direct control of catecholamines synthesis. In the present study, we evidenced
      the constitutive expression of functional cannabinoid CB(1) receptors in N1E-115
      neuroblastoma and reported on the use of this model to examine the influence of
      diverse cannabinoid ligands on TH expression. Exposure of the cells to the high
      affinity agonist HU 210 (5 h) resulted in a significant decrease in TH content
      (pEC(50): 6.40). In contrast, no change was observed after a similar treatment
      with the structurally unrelated agonist CP 55,940. Besides, the use of a
      luciferase reporter assay revealed that these two agonists showed opposite
      influences on TH gene promoter activity. Thus, in cells expressing pTH-luc
      constructs, inhibition and induction of luciferase activity were respectively
      observed with HU 210 (pEC(50): 8.95) and CP 55,940 (pEC(50): 9.09).
      Pharmacological characterisation revealed that these reciprocal responses were
      both related to the specific activation of cannabinoid CB(1) receptor, suggesting
      an agonist-dependent modulation of distinct signalling pathways. While these data
      points out the possible pharmacological manipulation of TH expression by
      cannabinoid ligands, such approach should take into account the existence of
      agonist selective trafficking of cannabinoid CB(1) receptor signalling.

PMID- 17540008
TI  - Hsp70/Hsc70 regulates the effect phosphorylation has on stabilizing ataxin-1.
AB  - Spinocerebellar ataxia type 1 (SCA1) is an inherited neurodegenerative disorder.
      The mutation causing SCA1 is an expansion in the polyglutamine tract of the ATXN1
      protein. Previous work demonstrated that phosphorylation of mutant ATXN1 at
      serine 776 (S776), a putative Akt phosphorylation site, is critical for
      pathogenesis. To examine this pathway further, we utilized a cell-transfection
      system that allowed the targeting of Akt to either the cytoplasm or the nucleus.
      In contrast to HeLa cells, we found that Akt targeted to the cytoplasm increased
      the degradation of ATXN1 in Chinese hamster ovary cells. However, Akt targeted to
      the cytoplasm failed to destabilize ATXN1 if Hsp70/Hsc70 was present. Thus,
      Hsp70/Hsc70 can regulate ATXN1 levels in concert with phosphorylation of ATXN1 at
      S776.

PMID- 17540009
TI  - Cholesterol supports the retinoic acid-induced synaptic vesicle formation in
      differentiating human SH-SY5Y neuroblastoma cells.
AB  - Synaptic vesicle formation, vesicle activation and exo/endocytosis in the pre
      synaptic area are central steps in neuronal communication. The formation and
      localization of synaptic vesicles in human SH-SY5Y neuroblastoma cells,
      differentiated with 12-o-tetradecanoyl-phorbol-13-acetate, dibutyryl cyclic AMP,
      all-trans-retinoic acid (RA) and cholesterol, was studied by fluorescence
      microscopy and immunocytochemical methods. RA alone or together with cholesterol,
      produced significant neurite extension and formation of cell-to-cell contacts.
      Synaptic vesicle formation was followed by anti-synaptophysin (SypI) and AM1-43
      staining. SypI was only weakly detected, mainly in cell somata, before 7 days in
      vitro, after which it was found in neurites. Depolarization of the differentiated
      cells with high potassium solution increased the number of fluorescent puncta, as
      well as SypI and AM1-43 co-localization. In addition to increase in the number of
      synaptic vesicles, RA and cholesterol also increased the number and distribution
      of lysosome-associated membrane protein 2 labeled lysosomes. RA-induced Golgi
      apparatus fragmentation was partly avoided by co-treatment with cholesterol. The
      SH-SY5Y neuroblastoma cell line, differentiated by RA and cholesterol and with
      good viability in culture, is a valuable tool for basic studies of neuronal
      metabolism, specifically as a model for dopaminergic neurons.

PMID- 17540010
TI  - Amyloid precursor protein knockdown by siRNA impairs spontaneous alternation in
      adult mice.
AB  - The cleavage-product of amyloid precursor protein (APP) constitutes the core
      component of plaques found in the brains of Alzheimer's disease (AD) patients.
      APP is ubiquitously expressed and its precise physiological functions remain
      unclear. This protein has been proposed to regulate synaptic function and
      processes underlying learning and memory. While APP knockout mice show behavioral
      impairments, these may occur due to early changes during development and/or due
      to abolition of APP function in adult. To investigate the acute effects of APP
      knockdown without involving developmental processes, APP expression was reduced
      using RNA interference in adult mouse brain. Small interfering RNAs (siRNAs) that
      down-regulated mouse APP protein levels (APP-siRNA) were identified using an APP
      plasmid-siRNA co-transfection assay in mouse NIH/3T3 fibroblast cells. Infusion
      of APP-siRNAs into the ventricular system for 2 weeks also down-regulated APP
      mRNA in mouse brain. Highest knockdown of APP mRNA levels was found in the CA2
      CA3 regions of the hippocampus. Mice treated with the most active APP-siRNA
      showed a significant reduction in spontaneous alternation rate in the Y-maze,
      without effects on forelimb grip strength or locomotor activity. These data
      suggest that acute knockdown of APP in adult mouse brain impairs hippocampus
      dependent spatial working memory.

PMID- 17540011
TI  - Hippocampal gene expression profiling reveals the possible involvement of Homer1
      and GABA(B) receptors in scopolamine-induced amnesia.
AB  - Scopolamine-treated rats are commonly used as a psychopharmacological model of
      memory dysfunction and have been extensively studied to establish the
      effectiveness of acetylcholinesterase inhibitors in the treatment of Alzheimer's
      disease. Scopolamine is a muscarinic acetylcholine receptor antagonist that
      induces memory deficits in young subjects similar to those occurring during
      aging. The amnesic effect of scopolamine is well established but the molecular
      and cellular mechanisms that sustain its neuropharmacological action are still
      unclear. The present genome wide study investigates hippocampal gene expression
      profiling in scopolamine-treated adult rats following stimulation in a spatial
      memory task. Using microarray and quantitative real-time RT-PCR approaches, we
      identified several genes previously known to be associated with memory processes
      (Homer1, GABA(B) receptor, early growth response 1, prodynorphin, VGF nerve
      growth factor inducible) and multiple novel candidate genes possibly involved in
      cognition (including calcium/calmodulin-dependent protein kinase kinase 2, dual
      specificity phosphatase 5 and 6, glycophorin C) that were altered following
      scopolamine treatment. Moreover, we found that stable over-expression of
      glutamatergic components Homer1a and 1c in the hippocampus of adult rats induced
      by recombinant adeno-associated virus vector abolished memory improvement
      produced by the GABA(B) receptor antagonist SGS742 in scopolamine-treated rats.
      Taken together, these results reveal novel genes and mechanisms involved in
      scopolamine-induced amnesia, and demonstrate the involvement of both GABA and
      glutamate neurotransmission in this animal model of cognitive dysfunctions.

PMID- 17540012
TI  - Nicotinic receptor activation by epibatidine induces heme oxygenase-1 and
      protects chromaffin cells against oxidative stress.
AB  - Activation of neuronal nicotinic acetylcholine receptors (nAChR) provides
      neuroprotection against different toxic stimuli that often lead to overproduction
      of reactive oxygen species (ROS) and cell death. ROS production has been related
      with disease progression in several neurodegenerative pathologies such as
      Alzheimer's or Parkinson's diseases. In this context, we investigated here if the
      exposure of bovine chromaffin cells to the potent nAChR agonist epibatidine
      protected against rotenone (30 micromol/L) plus oligomycin (10 micromol/L)
      (rot/oligo) toxicity, an in vitro model of mitochondrial ROS production.
      Epibatidine induced a concentration- and time-dependent protection, which was
      maximal at 3 mumol/L after 24 h. Pre-incubation with dantrolene (100 micromol/L)
      (a blocker of the ryanodine receptor channel), chelerythrine (1 micromol/L) (a
      protein kinase C inhibitor), or PD98059 (50 micromol/L) (a MEK inhibitor),
      aborted epibatidine-elicited cytoprotection. Mitochondrial depolarization, ROS,
      and caspase 3 active produced by rot/oligo were also prevented by epibatidine.
      Epibatidine doubled the amount of heme oxygenase-1 (HO-1), a critical cell
      defence enzyme against oxidative stress. Furthermore, the HO-1 inhibitor Sn(IV)
      protoporphyrin IX dichloride reversed the epibatidine protecting effects and HO-1
      inducer Co (III) protoporphyrin IX dichloride exhibited neuroprotective effects
      by itself. The results of this study point to HO-1 as the cytoprotective target
      of nAChR activation through the following pathway: endoplasmic reticulum Ca(2+)
      induced Ca(2+)-release activates the protein kinase C/extracellular regulated
      kinase/HO-1 axis to mitigate mitochondrial depolarization and ROS production.
      This study provides a mechanistic insight on how nAChR activation translates into
      an antioxidant and antiapoptotic signal through up-regulation of HO-1.

PMID- 17540013
TI  - Patients with persistent medically unexplained symptoms in general practice:
      characteristics and quality of care.
AB  - BACKGROUND: Medically unexplained physical symptoms (MUPS) are common in general
      practice (GP), and are even more problematic as they become persistent. The
      present study examines the relationship between persistent MUPS in general
      practice on the one hand and quality of life, social conditions, and coping on
      the other hand. Additionally, it is examined how patients with persistent MUPS
      evaluate the quality of GP-care. METHODS: Data were used from a representative
      survey of morbidity in Dutch general practice, in which data from the electronic
      medical records were extracted. A random sample of patients participated in an
      extensive health interview and completed self-reported measures on social
      isolation, coping and the quality of GP-care. Patients with persistent MUPS (N =
      192) were compared with general practice patients not meeting the criteria for
      persistent MUPS (N = 7.314), and with a group of patients that visited the GP in
      comparable rates for medical diagnoses (N = 2.265). Multiple logistic regression
      analyses were used to control for relevant socio-demographic variables and
      chronic diseases. RESULTS: After adjustment for demographics and chronic
      diseases, patients with persistent MUPS reported more psychological distress,
      more functional impairment, more social isolation, and they evaluated the quality
      of GP-care less positive than the other two patient groups. Although the majority
      of MUPS patients were positive about the quality of GP-care, they more often felt
      that they were not taken seriously or not involved in treatment decisions, and
      more often reported that the GP did not take sufficient time. The three groups
      did not differ with respect to the statement that the GP unnecessarily explains
      physical problems as psychological ones. CONCLUSION: Strengthening MUPS patients'
      social network and encouraging social activities may be a meaningful intervention
      in which the GP may play a stimulating role. To further improve MUPS patients'
      satisfaction with GP-care, GPs may pay extra attention to taking sufficient time
      when treating MUPS patients, taking the problems seriously, and involving them in
      treatment decisions.

PMID- 17540014
TI  - RNAstrand: reading direction of structured RNAs in multiple sequence alignments.
AB  - MOTIVATION: Genome-wide screens for structured ncRNA genes in mammals,
      urochordates, and nematodes have predicted thousands of putative ncRNA genes and
      other structured RNA motifs. A prerequisite for their functional annotation is to
      determine the reading direction with high precision. RESULTS: While folding
      energies of an RNA and its reverse complement are similar, the differences are
      sufficient at least in conjunction with substitution patterns to discriminate
      between structured RNAs and their complements. We present here a support vector
      machine that reliably classifies the reading direction of a structured RNA from a
      multiple sequence alignment and provides a considerable improvement in
      classification accuracy over previous approaches. SOFTWARE: RNAstrand is freely
      available as a stand-alone tool from http://www.bioinf.uni
      leipzig.de/Software/RNAstrand and is also included in the latest release of RNAz,
      a part of the Vienna RNA Package.

PMID- 17540015
TI  - The functioning of the Cuban home hospitalization programme: a descriptive
      analysis.
AB  - BACKGROUND: Over the last decades hospital at home (HaH) programmes have been set
      up in many, mainly European, countries. The Cuban HaH programme is not hospital
      driven, but the responsibility of the first line health services, and family
      doctors play a pivotal role. METHODS: We analyse the structure and functioning of
      the Cuban programme. In this descriptive study, information was prospectively
      collected on HaH patients admitted between July 1st 2001 and June 30th 2002.
      RESULTS: Admission rates varied between areas from 0.014 to 0.035 per person per
      year (ppy). The < 1 y and 1-4 y age groups had the highest admission rates. In
      one area the follow-up of pregnancy problems led to high 15-24 y and 25-49 y
      female admission rates (0,070 and 0,058 respectively). Respiratory affections
      were the most frequent reason for admission (32,6%), followed by early hospital
      discharge (16,0%) and gynaeco-obstetrical problems (10.8%). The median length of
      stay varied from 5 to 7 days between regions and from 5 days (early discharge) to
      7 days (gynaeco-obstetrical problems) in function of the reason for admission. On
      average an HaH episode entailed 1.4 and 1.6 contacts per patient-day with the
      family doctor and nurse respectively. CONCLUSION: Difference in admission
      criteria in function of geography, distance to the hospital, transport
      facilities, and staff factors, as well as differences in hospital policy on early
      discharge explain the observed variability. The programme plays an important role
      in the integrated approach to quality care in the Cuban health system, but could
      benefit from more uniform admission criteria.

PMID- 17540016
TI  - Unexpected species diversity of Malagasy primates (Lepilemur spp.) in the same
      biogeographical zone: a morphological and molecular approach with the description
      of two new species.
AB  - BACKGROUND: The lemurs of Madagascar provide an excellent mammalian radiation to
      explore mechanisms and processes favouring species diversity and evolution.
      Species diversity, in particular of nocturnal species, increased considerably
      during the last decade. However, the factors contributing to this high diversity
      are not well understood. We tested predictions derived from two existing
      biogeographic models by exploring the genetic and morphological divergence among
      populations of a widely distributed lemur genus, the sportive lemur (Lepilemur
      ssp.) along a 560 km long transect from western to northern Madagascar. RESULTS:
      By using the phylogenetic analyses of mtDNA sequence data, molecular diagnostic
      sites and phenotypic morphometric traits, we uncovered two previously undetected
      species whose distributions contradict the two existing biogeographic models.
      Brief species descriptions are provided and a new biogeographic model is proposed
      (the "large river model"). CONCLUSION: According to the "large river model",
      large rivers in north and northwestern Madagascar acted as geographical barriers
      for gene flow and facilitated speciation events on a much smaller spatial scale
      than previously thought. Thereby, this study does not only show that species
      diversity in nocturnal Malagasy primates is continuously underestimated but aims
      to emphasize the need for conservation actions if those species with small ranges
      shall not face extinction in the near future.

PMID- 17540017
TI  - Validation of reference genes for quantitative RT-PCR studies in porcine oocytes
      and preimplantation embryos.
AB  - BACKGROUND: In the developing embryo, total RNA abundance fluctuates caused by
      functional RNA degradation and zygotic genome activation. These variations in the
      transcriptome in early development complicate the choice of good reference genes
      for gene expression studies by quantitative real time polymerase chain reaction.
      RESULTS: In order to identify stably expressed genes for normalisation of
      quantitative data, within early stages of development, transcription levels were
      examined of 7 frequently used reference genes (B2M, BACT, GAPDH, H2A, PGK1, SI8,
      and UBC) at different stages of early porcine embryonic development (germinal
      vesicle, metaphase-2, 2-cell, 4-cell, early blastocyst, expanded blastocyst).
      Analysis of transcription profiling by geNorm software revealed that GAPDH, PGK1,
      S18, and UBC showed high stability in early porcine embryonic development, while
      transcription levels of B2M, BACT, and H2A were highly regulated. CONCLUSION:
      Good reference genes that reflect total RNA content were identified in early
      embryonic development from oocyte to blastocyst. A selection of either GAPDH or
      PGK1, together with ribosomal protein S18 (S18), and UBC is proposed as reference
      genes, but the use of B2M, BACT, or H2A is discouraged.

PMID- 17540018
TI  - Inactivation properties of sodium channel Nav1.8 maintain action potential
      amplitude in small DRG neurons in the context of depolarization.
AB  - BACKGROUND: Small neurons of the dorsal root ganglion (DRG) express five of the
      nine known voltage-gated sodium channels. Each channel has unique biophysical
      characteristics which determine how it contributes to the generation of action
      potentials (AP). To better understand how AP amplitude is maintained in
      nociceptive DRG neurons and their centrally projecting axons, which are subjected
      to depolarization within the dorsal horn, we investigated the dependence of AP
      amplitude on membrane potential, and how that dependence is altered by the
      presence or absence of sodium channel Nav1.8. RESULTS: In small neurons cultured
      from wild type (WT) adult mouse DRG, AP amplitude decreases as the membrane
      potential is depolarized from -90 mV to -30 mV. The decrease in amplitude is best
      fit by two Boltzmann equations, having V1/2 values of -73 and -37 mV. These
      values are similar to the V1/2 values for steady-state fast inactivation of
      tetrodotoxin-sensitive (TTX-s) sodium channels, and the tetrodotoxin-resistant
      (TTX-r) Nav1.8 sodium channel, respectively. Addition of TTX eliminates the more
      hyperpolarized V1/2 component and leads to increasing AP amplitude for holding
      potentials of -90 to -60 mV. This increase is substantially reduced by the
      addition of potassium channel blockers. In neurons from Nav1.8(-/-) mice, the
      voltage-dependent decrease in AP amplitude is characterized by a single Boltzmann
      equation with a V1/2 value of -55 mV, suggesting a shift in the steady-state fast
      inactivation properties of TTX-s sodium channels. Transfection of Nav1.8(-/-) DRG
      neurons with DNA encoding Nav1.8 results in a membrane potential-dependent
      decrease in AP amplitude that recapitulates WT properties. CONCLUSION: We
      conclude that the presence of Nav1.8 allows AP amplitude to be maintained in DRG
      neurons and their centrally projecting axons even when depolarized within the
      dorsal horn.

PMID- 17540019
TI  - The stochastic behavior of a molecular switching circuit with feedback.
AB  - BACKGROUND: Using a statistical physics approach, we study the stochastic
      switching behavior of a model circuit of multisite phosphorylation and
      dephosphorylation with feedback. The circuit consists of a kinase and phosphatase
      acting on multiple sites of a substrate that, contingent on its modification
      state, catalyzes its own phosphorylation and, in a symmetric scenario,
      dephosphorylation. The symmetric case is viewed as a cartoon of conflicting
      feedback that could result from antagonistic pathways impinging on the state of a
      shared component. RESULTS: Multisite phosphorylation is sufficient for bistable
      behavior under feedback even when catalysis is linear in substrate concentration,
      which is the case we consider. We compute the phase diagram, fluctuation spectrum
      and large-deviation properties related to switch memory within a statistical
      mechanics framework. Bistability occurs as either a first-order or second-order
      non-equilibrium phase transition, depending on the network symmetries and the
      ratio of phosphatase to kinase numbers. In the second-order case, the circuit
      never leaves the bistable regime upon increasing the number of substrate
      molecules at constant kinase to phosphatase ratio. CONCLUSION: The number of
      substrate molecules is a key parameter controlling both the onset of the bistable
      regime, fluctuation intensity, and the residence time in a switched state. The
      relevance of the concept of memory depends on the degree of switch symmetry, as
      memory presupposes information to be remembered, which is highest for equal
      residence times in the switched states.

PMID- 17540020
TI  - A perturbation-based balance training program for older adults: study protocol
      for a randomised controlled trial.
AB  - BACKGROUND: Previous research investigating exercise as a means of falls
      prevention in older adults has shown mixed results. Lack of specificity of the
      intervention may be an important factor contributing to negative results. Change
      in-support (CIS) balance reactions, which involve very rapid stepping or grasping
      movements of the limbs, play a critical role in preventing falls; hence, a
      training program that improves ability to execute effective CIS reactions could
      potentially have a profound effect in reducing risk of falling. This paper
      describes: 1) the development of a perturbation-based balance training program
      that targets specific previously-reported age-related impairments in CIS
      reactions, and 2) a study protocol to evaluate the efficacy of this new training
      program. METHODS/DESIGN: The training program involves use of unpredictable,
      multi-directional moving-platform perturbations to evoke stepping and grasping
      reactions. Perturbation magnitude is gradually increased over the course of the 6
      week program, and concurrent cognitive and movement tasks are included during
      later sessions. The program was developed in accordance with well-established
      principles of motor learning, such as individualisation, specificity, overload,
      adaptation-progression and variability. Specific goals are to reduce the
      frequency of multiple-step responses, reduce the frequency of collisions between
      the stepping foot and stance leg, and increase the speed of grasping reactions. A
      randomised control trial will be performed to evaluate the efficacy of the
      training program. A total of 30 community-dwelling older adults (age 64-80) with
      a recent history of instability or falling will be assigned to either the
      perturbation-based training or a control group (flexibility/relaxation training),
      using a stratified randomisation that controls for gender, age and baseline
      stepping/grasping performance. CIS reactions will be tested immediately before
      and after the six weeks of training, using platform perturbations as well as a
      distinctly different method of perturbation (waist pulls) in order to evaluate
      the generalisability of the training effects. DISCUSSION: This study will
      determine whether perturbation-based balance training can help to reverse
      specific age-related impairments in balance-recovery reactions. These results
      will help to guide the development of more effective falls prevention programs,
      which may ultimately lead to reduced health-care costs and enhanced mobility,
      independence and quality of life.

PMID- 17540021
TI  - BDNF promotes target innervation of Xenopus mandibular trigeminal axons in vivo.
AB  - BACKGROUND: Trigeminal nerves consist of ophthalmic, maxillary, and mandibular
      branches that project to distinct regions of the facial epidermis. In Xenopus
      embryos, the mandibular branch of the trigeminal nerve extends toward and
      innervates the cement gland in the anterior facial epithelium. The cement gland
      has previously been proposed to provide a short-range chemoattractive signal to
      promote target innervation by mandibular trigeminal axons. Brain derived
      neurotrophic factor, BDNF is known to stimulate axon outgrowth and branching. The
      goal of this study is to determine whether BDNF functions as the proposed target
      recognition signal in the Xenopus cement gland. RESULTS: We found that the cement
      gland is enriched in BDNF mRNA transcripts compared to the other neurotrophins
      NT3 and NT4 during mandibular trigeminal nerve innervation. BDNF knockdown in
      Xenopus embryos or specifically in cement glands resulted in the failure of
      mandibular trigeminal axons to arborise or grow into the cement gland. BDNF
      expressed ectodermal grafts, when positioned in place of the cement gland,
      promoted local trigeminal axon arborisation in vivo. CONCLUSION: BDNF is
      necessary locally to promote end stage target innervation of trigeminal axons in
      vivo, suggesting that BDNF functions as a short-range signal that stimulates
      mandibular trigeminal axon arborisation and growth into the cement gland.

PMID- 17540022
TI  - Psychometric properties of a prostate cancer radiation late toxicity
      questionnaire.
AB  - BACKGROUND: To construct a short prostate cancer radiation late toxicity (PCRT)
      questionnaire with health-related quality-of-life (HRQoL) domains. METHODS: The
      PCRT was developed by item generation, questionnaire construction (n = 7 experts,
      n = 8 focus group patients), pilot testing (n = 37), item reduction (n = 100),
      reliability testing (n = 237), and validity testing (n = 274). RESULTS:
      Reliability of the three item-reduced subscales demonstrated intraclass
      correlation coefficients (CC) of 0.811 (GU), 0.842 (GI), and 0.740 (sexual).
      Discriminant validity demonstrated Pearson CC of 0.449 (GU-GI), 0.200 (sexual
      GU), and 0.09 (sexual-GI). Content validity correlations between PCRT-PCQoL were
      0.35-0.78, PCRT-FACT-G(c) were 0.19-0.39, and PCRT-SF-36(R) were 0.03-0.34.
      CONCLUSION: We successfully generated a PCRT HRQoL questionnaire including
      subscales with very good psychometric properties.

PMID- 17540023
TI  - Oral pirfenidone in patients with chronic fibrosis resulting from radiotherapy: a
      pilot study.
AB  - BACKGROUND: Fibrosis is a common side effect after treatment with ionizing
      radiation. Several methods to ameliorate debilitating fibrosis have been employed
      but without consistent results. The goal of this pilot study is to determine if
      Pirfenidone, a novel regulator of cytokine gene expression, has the potential to
      ameliorate established radiation-induced fibrosis. METHODS: Open label,
      prospective pilot study of 800 mg three times/day, orally administered
      Pirfenidone was administered to enrolled patients who were had completed
      radiation therapy and who had established radiation-induced fibrosis. Range of
      motion (ROM) was assessed using standard measures, and subjective measures of
      pain, fatigue, disability and global health were measured every three months.
      RESULTS: Seven patients were enrolled of whom 3 had ROM assessments of 1 site and
      2 had ROM assessments of 2 sites. Of these assessments, 6 revealed increased ROM
      during drug intervention while 1 revealed a decreased ROM. There was an overall
      improvement in the mental composite score of the SF36 while physical composite
      score was decreased and the vitality score was unchanged. Two patients were
      removed from the study because of syncopal episodes. CONCLUSION: Several patients
      experienced improved function of at least 25% and reported subjective
      improvement. Pirfenidone may benefit patients with radiation-induced fibrosis and
      is worthy of a larger well controlled trial.

PMID- 17540024
TI  - Do citizens have minimum medical knowledge? A survey.
AB  - BACKGROUND: Experts defined a "minimum medical knowledge" (MMK) that people need
      for understanding typical signs and/or risk factors of four relevant clinical
      conditions: myocardial infarction, stroke, chronic obstructive pulmonary disease
      and HIV/AIDS. We tested to what degree Swiss adult citizens satisfy this
      criterion for MMK and whether people with medical experience have acquired better
      knowledge than those without. METHODS: Questionnaire interview in a Swiss urban
      area with 185 Swiss citizens (median age 29 years, interquartile range 23 to 49,
      52% male). We obtained context information on age, gender, highest educational
      level, (para)medical background and specific health experience with one of the
      conditions in the social surrounding. We calculated the proportion of MMK and
      examined whether citizens with medical background (personal or professional)
      would perform better compared to other groups. RESULTS: No single citizen reached
      the full MMK (100%). The mean MMK was as low as 32% and the range was 0-72%.
      Surprisingly, multivariable analysis showed that participants with a university
      degree (n = 84; beta (95% CI) +3.7% MMK (0.4-7.1) p = 0.03), (para)medical
      background (n = 34; +6.2% MMK (2.0-10.4), p = 0.004) and personal illness
      experience (n = 96; +4.9% MMK (1.5-8.2), p = 0.004) had only a moderately higher
      MMK than those without, while age and sex had no effect on the level of MMK.
      Interaction between university degree and clinical experience (personal or
      professional) showed no effect suggesting that higher education lacks synergistic
      effect. CONCLUSION: This sample of Swiss citizens did not know more than a third
      of the MMK. We found little difference within groups with medical experience
      (personal or professional), suggesting that there is a consistent and dramatic
      lack of knowledge in the general public about the typical signs and risk factors
      of relevant clinical conditions.

PMID- 17540025
TI  - Promoting contraceptive use among unmarried female migrants in one factory in
      Shanghai: a pilot workplace intervention.
AB  - BACKGROUND: In urban China, more single women are becoming pregnant and resorting
      to induced abortion, despite the wide availability of temporary methods of
      contraception. We developed and piloted a workplace-based intervention to promote
      contraceptive use in unmarried female migrants working in privately owned
      factories. METHODS: Quasi-experimental design. In consultation with clients, we
      developed a workplace based intervention to promote contraception use in
      unmarried female migrants in a privately owned factory. We then implemented this
      in one factory, using a controlled before-and-after design. The intervention
      included lectures, bespoke information leaflets, and support to the factory
      doctors in providing a contraceptive service. RESULTS: 598 women participated:
      most were under 25, migrants to the city, with high school education. Twenty
      percent were lost when staff were made redundant, and implementation was
      logistically complicated. All women attended the initial lecture, and just over
      half the second lecture. Most reported reading the educational material provided
      (73%), but very few women reported using the free family planning services
      offered at the factory clinic (5%) or the Family Planning Institute (3%). At
      baseline, 90% (N = 539) stated that contraceptives were required if having sex
      before marriage; of those reporting sex in the last three months, the majority
      reporting using contraceptives (78%, 62/79) but condom use was low (44%, 35/79).
      Qualitative data showed that the reading material seemed to be popular and young
      women expressed a need for more specific reproductive health information,
      particularly on HIV/AIDS. Women wanted services with some privacy and anonymity,
      and views on the factory service were mixed. CONCLUSION: Implementing a complex
      intervention with a hard to reach population through a factory in China, using a
      quasi-experimental design, is not easy. Further research should focus on the
      specific needs and service preferences of this population and these should be
      considered in any policy reform so that contraceptive use may be encouraged among
      young urban migrant workers.

PMID- 17540026
TI  - On the origin of the translation system and the genetic code in the RNA world by
      means of natural selection, exaptation, and subfunctionalization.
AB  - BACKGROUND: The origin of the translation system is, arguably, the central and
      the hardest problem in the study of the origin of life, and one of the hardest in
      all evolutionary biology. The problem has a clear catch-22 aspect: high
      translation fidelity hardly can be achieved without a complex, highly evolved set
      of RNAs and proteins but an elaborate protein machinery could not evolve without
      an accurate translation system. The origin of the genetic code and whether it
      evolved on the basis of a stereochemical correspondence between amino acids and
      their cognate codons (or anticodons), through selectional optimization of the
      code vocabulary, as a "frozen accident" or via a combination of all these routes
      is another wide open problem despite extensive theoretical and experimental
      studies. Here we combine the results of comparative genomics of translation
      system components, data on interaction of amino acids with their cognate codons
      and anticodons, and data on catalytic activities of ribozymes to develop
      conceptual models for the origins of the translation system and the genetic code.
      RESULTS: Our main guide in constructing the models is the Darwinian Continuity
      Principle whereby a scenario for the evolution of a complex system must consist
      of plausible elementary steps, each conferring a distinct advantage on the
      evolving ensemble of genetic elements. Evolution of the translation system is
      envisaged to occur in a compartmentalized ensemble of replicating, co-selected
      RNA segments, i.e., in a RNA World containing ribozymes with versatile
      activities. Since evolution has no foresight, the translation system could not
      evolve in the RNA World as the result of selection for protein synthesis and must
      have been a by-product of evolution drive by selection for another function,
      i.e., the translation system evolved via the exaptation route. It is proposed
      that the evolutionary process that eventually led to the emergence of translation
      started with the selection for ribozymes binding abiogenic amino acids that
      stimulated ribozyme-catalyzed reactions. The proposed scenario for the evolution
      of translation consists of the following steps: binding of amino acids to a
      ribozyme resulting in an enhancement of its catalytic activity; evolution of the
      amino-acid-stimulated ribozyme into a peptide ligase (predecessor of the large
      ribosomal subunit) yielding, initially, a unique peptide activating the original
      ribozyme and, possibly, other ribozymes in the ensemble; evolution of self
      charging proto-tRNAs that were selected, initially, for accumulation of amino
      acids, and subsequently, for delivery of amino acids to the peptide ligase;
      joining of the peptide ligase with a distinct RNA molecule (predecessor of the
      small ribosomal subunit) carrying a built-in template for more efficient,
      complementary binding of charged proto-tRNAs; evolution of the ability of the
      peptide ligase to assemble peptides using exogenous RNAs as template for
      complementary binding of charged proteo-tRNAs, yielding peptides with the
      potential to activate different ribozymes; evolution of the translocation
      function of the protoribosome leading to the production of increasingly longer
      peptides (the first proteins), i.e., the origin of translation. The specifics of
      the recognition of amino acids by proto-tRNAs and the origin of the genetic code
      depend on whether or not there is a physical affinity between amino acids and
      their cognate codons or anticodons, a problem that remains unresolved.
      CONCLUSION: We describe a stepwise model for the origin of the translation system
      in the ancient RNA world such that each step confers a distinct advantage onto an
      ensemble of co-evolving genetic elements. Under this scenario, the primary cause
      for the emergence of translation was the ability of amino acids and peptides to
      stimulate reactions catalyzed by ribozymes. Thus, the translation system might
      have evolved as the result of selection for ribozymes capable of, initially,
      efficient amino acid binding, and subsequently, synthesis of increasingly
      versatile peptides. Several aspects of this scenario are amenable to experimental
      testing.

PMID- 17540027
TI  - The cosmological model of eternal inflation and the transition from chance to
      biological evolution in the history of life.
AB  - BACKGROUND: Recent developments in cosmology radically change the conception of
      the universe as well as the very notions of "probable" and "possible". The model
      of eternal inflation implies that all macroscopic histories permitted by laws of
      physics are repeated an infinite number of times in the infinite multiverse. In
      contrast to the traditional cosmological models of a single, finite universe,
      this worldview provides for the origin of an infinite number of complex systems
      by chance, even as the probability of complexity emerging in any given region of
      the multiverse is extremely low. This change in perspective has profound
      implications for the history of any phenomenon, and life on earth cannot be an
      exception. HYPOTHESIS: Origin of life is a chicken and egg problem: for
      biological evolution that is governed, primarily, by natural selection, to take
      off, efficient systems for replication and translation are required, but even
      barebones cores of these systems appear to be products of extensive selection.
      The currently favored (partial) solution is an RNA world without proteins in
      which replication is catalyzed by ribozymes and which serves as the cradle for
      the translation system. However, the RNA world faces its own hard problems as
      ribozyme-catalyzed RNA replication remains a hypothesis and the selective
      pressures behind the origin of translation remain mysterious. Eternal inflation
      offers a viable alternative that is untenable in a finite universe, i.e., that a
      coupled system of translation and replication emerged by chance, and became the
      breakthrough stage from which biological evolution, centered around Darwinian
      selection, took off. A corollary of this hypothesis is that an RNA world, as a
      diverse population of replicating RNA molecules, might have never existed. In
      this model, the stage for Darwinian selection is set by anthropic selection of
      complex systems that rarely but inevitably emerge by chance in the infinite
      universe (multiverse). CONCLUSION: The plausibility of different models for the
      origin of life on earth directly depends on the adopted cosmological scenario. In
      an infinite universe (multiverse), emergence of highly complex systems by chance
      is inevitable. Therefore, under this cosmology, an entity as complex as a coupled
      translation-replication system should be considered a viable breakthrough stage
      for the onset of biological evolution. REVIEWERS: This article was reviewed by
      Eric Bapteste, David Krakauer, Sergei Maslov, and Itai Yanai.

PMID- 17540028
TI  - Functioning in individuals with chronic fatigue syndrome: increased impairment
      with co-occurring multiple chemical sensitivity and fibromyalgia.
AB  - BACKGROUND: Chronic fatigue syndrome (CFS), multiple chemical sensitivity (MCS),
      and fibromyalgia (FM) commonly co-occur. Some propose that CFS, MCS, and FM are
      manifestations of the same illness based on high rates of co-occurrence and
      overlapping diagnostic criteria. This study seeks to differentiate these
      diagnoses by comparing individuals with one or more illness on functioning,
      psychiatric comorbidity, coping style, and in vivo physical measures. METHODS:
      Participants included 114 men and women who met criteria for CFS. FM was
      diagnosed during a physical examination, and MCS was assessed using a
      questionnaire. Participants were divided into four groups: CFS alone, CFS-MCS,
      CFS-FM, and CFS-MCS-FM. Self-report measures, a psychiatric interview, and in
      vivo physical measures were given. RESULTS: 43.9% met criteria for CFS alone,
      23.7% met criteria for CFS-MCS, 15.8% met criteria for CFS-FM, and 16.7% met
      criteria for CFS-MCS-FM. The CFS-MCS-FM group was more disabled than the CFS
      alone group on measures of physical functioning, general health, and bodily pain.
      In vivo measures did not differ, but the CFS-MCS-FM group rated exertion higher
      than the CFS alone group. CONCLUSION: Individuals with CFS alone were the highest
      functioning group across several domains, such as disability, depression, and
      severity of symptoms. Participants with three diagnoses experienced the greatest
      amount of disability. While substantial co-occurrence of these illnesses was
      found, this study provides evidence that having more than one illness exacerbates
      one's disability beyond CFS alone.

PMID- 17540029
TI  - NGF-mediated transcriptional targets of p53 in PC12 neuronal differentiation.
AB  - BACKGROUND: p53 is recognized as a critical regulator of the cell cycle and
      apoptosis. Mounting evidence also suggests a role for p53 in differentiation of
      cells including neuronal precursors. We studied the transcriptional role of p53
      during nerve growth factor-induced differentiation of the PC12 line into neuron
      like cells. We hypothesized that p53 contributed to PC12 differentiation through
      the regulation of gene targets distinct from its known transcriptional targets
      for apoptosis or DNA repair. RESULTS: Using a genome-wide chromatin
      immunoprecipitation cloning technique, we identified and validated 14 novel p53
      regulated genes following NGF treatment. The data show p53 protein was
      transcriptionally activated and contributed to NGF-mediated neurite outgrowth
      during differentiation of PC12 cells. Furthermore, we describe stimulus-specific
      regulation of a subset of these target genes by p53. The most salient
      differentiation-relevant target genes included wnt7b involved in dendritic
      extension and the tfcp2l4/grhl3 grainyhead homolog implicated in ectodermal
      development. Additional targets included brk, sdk2, sesn3, txnl2, dusp5, pon3,
      lect1, pkcbpb15 and other genes. CONCLUSION: Within the PC12 neuronal context,
      putative p53-occupied genomic loci spanned the entire Rattus norvegicus genome
      upon NGF treatment. We conclude that receptor-mediated p53 transcriptional
      activity is involved in PC12 differentiation and may suggest a contributory role
      for p53 in neuronal development.

PMID- 17540030
TI  - Incidence and characteristics of distal radius fractures in a southern Swedish
      region.
AB  - BACKGROUND: The incidence of distal radius fracture has increased substantially
      during the last 50 years according to several studies that estimated the overall
      incidence in various general populations. The incidence of fracture classified
      according to severity has not been well documented. The aim of this population
      based study was to estimate the overall and type-specific incidence rates of
      distal radius fracture in a representative population in southern Sweden.
      METHODS: During 2001, all persons older than 18 years with acute distal radius
      fracture in the southern Swedish region of Northeastern Scania were prospectively
      recorded. A radiologist classified the fractures according to the AO system and
      measured volar tilt and ulnar variance. A fracture with volar tilt outside a
      range of -5 degrees to 20 degrees and/or ulnar variance of 2 mm or greater was
      defined as displaced. RESULTS: 335 persons with acute distal radius fracture were
      recorded during the 1-year period. The overall incidence rate was 26 (95%
      confidence interval 23-29) per 10,000 person-years. Among women the incidence
      rate increased rapidly from the age of 50 and reached a peak of 119 per 10,000
      person-years in women 80 years and older. The incidence rate among women 50 to 79
      years old (56 per 10,000 person-years) was lower than that reported in previous
      studies of similar populations. Among men the incidence rate was low until the
      age of 80 years and older when it increased to 28 per 10,000 person-years.
      Fractures classified as AO type A comprised about 80% of the fractures in women
      and 64% in men. Almost two-thirds of all fractures were displaced and among men
      and women 80 years and older more than 80% of the fractures were displaced.
      CONCLUSION: The incidence rate of distal radius fracture in women 50 to 79 years
      old was lower than previously reported, which may indicate declining incidence in
      this group. In both sexes, the incidence was highest in the age group of 80 years
      and older. With a growing number of elderly in the general population, the impact
      of distal radius fracture in the future may be considerable.

PMID- 17540031
TI  - M. tuberculosis genotypic diversity and drug susceptibility pattern in HIV
      infected and non-HIV-infected patients in northern Tanzania.
AB  - BACKGROUND: Tuberculosis (TB) is a major health problem and HIV is the major
      cause of the increase in TB. Sub-Saharan Africa is endemic for both TB and HIV
      infection. Determination of the prevalence of M. tuberculosis strains and their
      drug susceptibility is important for TB control.TB positive culture, BAL fluid or
      sputum samples from 130 patients were collected and genotyped. The spoligotypes
      were correlated with anti-tuberculous drug susceptibility in HIV-infected and non
      HIV patients from Tanzania. RESULTS: One-third of patients were TB/HIV co
      infected. Forty-seven spoligotypes were identified. Fourteen isolates (10.8%) had
      new and unique spoligotypes while 116 isolates (89.2%) belonged to 33 known
      spoligotypes. The major spoligotypes contained nine clusters: CAS1-Kili 30.0%,
      LAM11- ZWE 14.6%, ND 9.2%, EAI 6.2%, Beijing 5.4%, T-undefined 4.6%, CAS1-Delhi
      3.8%, T1 3.8% and LAM9 3.8%. Twelve (10.8%) of the 111 phenotypically tested
      strains were resistant to anti-TB drugs. Eight (7.2%) were monoresistant strains:
      7 to isoniazid (INH) and one to streptomycin. Four strains (3.5%) were resistant
      to multiple drugs: one (0.9%) was resistant to INH and streptomycin and the other
      three (2.7%) were MDR strains: one was resistant to INH, rifampicin and
      ethambutol and two were resistant to all four anti-TB drugs. Mutation in the katG
      gene codon 315 and the rpoB hotspot region showed a low and high sensitivity,
      respectively, as predictor of phenotypic drug resistance. CONCLUSION: CAS1-Kili
      and LAM11-ZWE were the most common families. Strains of the Beijing family and
      CAS1-Kili were not or least often associated with resistance, respectively. HIV
      status was not associated with spoligotypes, resistance or previous TB treatment.

PMID- 17540033
TI  - nuID: a universal naming scheme of oligonucleotides for illumina, affymetrix, and
      other microarrays.
AB  - BACKGROUND: Oligonucleotide probes that are sequence identical may have different
      identifiers between manufacturers and even between different versions of the same
      company's microarray; and sometimes the same identifier is reused and represents
      a completely different oligonucleotide, resulting in ambiguity and potentially
      mis-identification of the genes hybridizing to that probe. RESULTS: We have
      devised a unique, non-degenerate encoding scheme that can be used as a universal
      representation to identify an oligonucleotide across manufacturers. We have named
      the encoded representation 'nuID', for nucleotide universal identifier. Inspired
      by the fact that the raw sequence of the oligonucleotide is the true definition
      of identity for a probe, the encoding algorithm uniquely and non-degenerately
      transforms the sequence itself into a compact identifier (a lossless
      compression). In addition, we added a redundancy check (checksum) to validate the
      integrity of the identifier. These two steps, encoding plus checksum, result in
      an nuID, which is a unique, non-degenerate, permanent, robust and efficient
      representation of the probe sequence. For commercial applications that require
      the sequence identity to be confidential, we have an encryption schema for nuID.
      We demonstrate the utility of nuIDs for the annotation of Illumina microarrays,
      and we believe it has universal applicability as a source-independent naming
      convention for oligomers. REVIEWERS: This article was reviewed by Itai Yanai,
      Rong Chen (nominated by Mark Gerstein), and Gregory Schuler (nominated by David
      Lipman).

PMID- 17540032
TI  - Precursors and preinvasive lesions of the breast: the role of molecular
      prognostic markers in the diagnostic and therapeutic dilemma.
AB  - Precursors and preinvasive lesions of the breast include atypical ductal
      hyperplasia (ADH), ductal carcinoma in situ (DCIS), and lobular neoplasia (LN).
      There is a significant debate regarding the classification, diagnosis, prognosis
      and management of these lesions. This review article describes the current
      theories regarding the pathogenesis and molecular evolution of these lesions. It
      reviews the implication of a variety of molecules in the continuum of breast
      lesions: estrogen receptors (ER-alpha and ER-beta), c-erb-B2 (Her2/neu), p53, Ki
      67, bcl-2, E-cadherin, transforming growth factor-beta (TGF-beta), p27 (Kip1),
      p16 (INK4a), p21 (Waf1), vascular endothelial growth factor (VEGF). With respect
      to the aforementioned molecules, this article reviews their pathophysiological
      importance, and puts the stress on whether they confer additional risk for
      invasive breast cancer or not. This knowledge has the potential to be of
      importance in the therapeutic decisions presenting in the common clinical
      practice.

PMID- 17540034
TI  - sIR: siRNA Information Resource, a web-based tool for siRNA sequence design and
      analysis and an open access siRNA database.
AB  - BACKGROUND: RNA interference has revolutionized our ability to study the effects
      of altering the expression of single genes in mammalian (and other) cells through
      targeted knockdown of gene expression. In this report we describe a web-based
      computational tool, siRNA Information Resource (sIR), which consists of a new
      open source database that contains validation information about published siRNA
      sequences and also provides a user-friendly interface to design and analyze siRNA
      sequences against a chosen target sequence. RESULTS: The siRNA design tool
      described in this paper employs empirically determined rules derived from a meta
      analysis of the published data; it uses a weighted scoring system that determines
      the optimal sequence within a target mRNA and thus aids in the rational selection
      of siRNA sequences. This scoring system shows a non-linear correlation with the
      knockdown efficiency of siRNAs. sIR provides a fast, customized BLAST output for
      all selected siRNA sequences against a variety of databases so that the user can
      verify the uniqueness of the design. We have pre-designed siRNAs for all the
      known human genes (24,502) in the Refseq database. These siRNAs were pre-BLASTed
      against the human Unigene database to estimate the target specificity and all
      results are available online. CONCLUSION: Although most of the rules for this
      scoring system were influenced by previously published rules, the weighted
      scoring system provides better flexibility in designing an appropriate siRNA when
      compared to the un-weighted scoring system. sIR is not only a comprehensive tool
      used to design siRNA sequences and lookup pre-designed siRNAs, but it is also a
      platform where researchers can share information on siRNA design and use.

PMID- 17540035
TI  - Nasal septal teratoma in a child.
AB  - BACKGROUND: Teratoma is a rare developmental neoplasm that arises from
      totipotential tumor stem cells. Head and neck teratomas constitute about 10% of
      all cases. Only two cases of mature teratoma of the nasal septum have previously
      been documented in the world literature. CASE PRESENTATION: We present a case of
      histologically confirmed mature teratoma arising from the nasal septum in an
      eighteen month old Nigerian female who presented with a history of noisy
      breathing associated with recurrent rhinorrhea since birth. Physical examination
      revealed obstruction of the right nasal cavity by a pale fleshy mass. She
      underwent a total surgical excision and to date, after thirty one months follow
      up, she is free from recurrence. CONCLUSION: The prognosis for benign teratoma of
      the nasal septum is good following total surgical excision.

PMID- 17540036
TI  - Hook2 contributes to aggresome formation.
AB  - BACKGROUND: Aggresomes are pericentrosomal accumulations of misfolded proteins,
      chaperones and proteasomes. Their positioning near the centrosome, like that of
      other organelles, requires active, microtubule-dependent transport. Linker
      proteins that can associate with the motor protein dynein, organelles, and
      microtubules are thought to contribute to the active maintenance of the
      juxtanuclear localization of many membrane bound organelles and aggresomes. Hook
      proteins have been proposed to serve as adaptors for the association of cargos
      with dynein for transport on microtubules. Hook2 was shown to localize to the
      centrosome, bind centriolin, and contribute to centrosomal function. RESULTS:
      Here we show that overexpression of hook2 promotes the accumulation of the cystic
      fibrosis transmembrane regulator in aggresomes without altering its biochemical
      properties or its steady state level. A dominant negatively acting form of hook2
      that lacks the centriolin binding C-terminal inhibits aggresome formation.
      CONCLUSION: We propose that hook2 contributes to the establishment and
      maintenance of the pericentrosomal localization of aggresomes by promoting the
      microtubule-based delivery of protein aggregates to pericentriolar aggresomes.

PMID- 17540037
TI  - An assessment of serum leptin levels in patients with chronic viral hepatitis: a
      prospective study.
AB  - BACKGROUND: The role of leptin in the course of liver disease due to chronic
      viral hepatitis (CVH) remains controversial. Our aims were to investigate the
      relationship between serum leptin concentrations and the severity of liver
      disease in a cohort of subjects with HBeAg negative chronic hepatitis B (CHB) and
      C (CHC) and to analyze the effect of body composition, the leptin system and
      insulin resistance together with viral factors on virologic response to antiviral
      treatment. METHODS: We studied 50 (36 men) consecutive patients suffering from
      biopsy-proven CVH due to HBV (n = 25) or HCV (n = 25) infection. Thirty-two (17
      men) healthy volunteers served as controls. Levels of serum leptin and insulin
      were determined by immunoassays at baseline and at the end of the treatment.
      RESULTS: A significant association between serum leptin levels and the stage of
      hepatic fibrosis was noted; patients with cirrhosis presented higher serum leptin
      levels compared to those with lower fibrosis stage [CHB patients (17436 pg/ml vs
      6028.5 pg/ml, p = 0.03), CHC patients (18014 pg/ml vs 4385 pg/ml, p = 0.05]. An
      inverse correlation between lower leptin levels and response to lamivudine
      monotherapy was noted in patients with CHB; those with a virologic response
      presented lower serum leptin levels (5334 vs 13111.5 pg/ml; p-value = 0.003) than
      non-responders. In genotype 1 CHC patients, insulin resistance played a
      significant role in the response to antiviral therapy. CONCLUSION: Our data
      clearly suggest that cirrhosis due to CHB or CHC is associated with higher leptin
      levels. Increased serum leptin levels represent a negative prognostic factor for
      response to lamivudine monotherapy in patients with CHB. In CHC patients insulin
      resistance strongly influences the response to antiviral treatment in patients
      infected with genotype 1.

PMID- 17540038
TI  - A rare case of concomitant huge exophytic gastrointestinal stromal tumor of the
      stomach and Kasabach-Merritt phenomenon.
AB  - BACKGROUND: We report an extremely rare case of concomitant huge exophytic GIST
      of the stomach and Kasabach-Merritt phenomenon (KMP). CASE PRESENTATION: The
      patient was a 67-year-old man experiencing abdominal distension since September
      2006. A physical examination revealed a 25 x 30 cm hard mass that was palpable in
      the middle and lower left abdomen minimal intrinsic mobility and massive ascites.
      Since the admitted patient was diagnosed with DIC, surgery could not be
      performed. The patient received a platelet transfusion and the DIC was treated.
      Due to this treatment, the platelet count recovered to 7.0 x 10(4); tumor
      resection was performed at 16 days after admission. Laparotomy revealed a huge
      extraluminal tumor arising from the greater curvature of the stomach that
      measured 25 x 30 cm and had not ruptured into the peritoneal cavity or
      infiltrated other organs. Partial gastric resection was performed. The resected
      mass measured 25 x 25 x 20 cm. In cross section, the tumor appeared hard and
      homogenous with a small polycystic area. Histopathology of the resected specimen
      showed large spindle cell GIST with >5/50 HPF (high-power field) mitotic
      activity. The postoperative course was uneventful, and the coagulopathy improved
      rapidly. CONCLUSION: Since the characteristic of tumor in this case was
      hypervascularity with bleeding and necrotic lesions, coagulopathy was thought to
      be caused by the trapping of platelets within a large vasculized tumor mass.

PMID- 17540039
TI  - A set of stage-specific gene transcripts identified in EK stage X and HH stage 3
      chick embryos.
AB  - BACKGROUND: The embryonic developmental process in avian species is quite
      different from that in mammals. The first cleavage begins 4 h after
      fertilization, but the first differentiation does not occur until laying of the
      egg (Eyal-Giladi and Kochav (EK) stage X). After 12 to 13 h of incubation
      (Hamburger and Hamilton (HH) stage 3), the three germ layers form and germ cell
      segregation in the early chick embryo are completed. Thus, to identify genes
      associated with early embryonic development, we compared transcript expression
      patterns between undifferentiated (stage X) and differentiated (HH stage 3)
      embryos. RESULTS: Microarray analysis primarily showed 40 genes indicating the
      significant changes in expression levels between stage X and HH stage 3, and 80%
      of the genes (32/40) were differentially expressed with more than a twofold
      change. Among those, 72% (23/32) were relatively up-regulated at stage X compared
      to HH stage 3, while 28% (9/32) were relatively up-regulated at HH stage 3
      compared to stage X. Verification and gene expression profiling of these GeneChip
      expression data were performed using quantitative RT-PCR for 32 genes at
      developmental four points; stage X (0 h), HH stage 3 (12 h), HH stage 6 (24 h),
      and HH stage 9 (30 h). Additionally, we further analyzed four genes with less
      than twofold expression increase at HH stage 3. As a result, we identified a set
      of stage-specific genes during the early chick embryo development; 21 genes were
      relatively up-regulated in the stage X embryo and 12 genes were relatively up
      regulated in the HH stage 3 embryo based on both results of microarray and
      quantitative RT-PCR. CONCLUSION: We identified a set of genes with stage-specific
      expression from microarray Genechip and quantitative RT-PCR. Discovering stage
      specific genes will aid in uncovering the molecular mechanisms involved the
      formation of the three germ layers and germ cell segregation in the early chick
      embryos.

PMID- 17540040
TI  - Selection of DDX5 as a novel internal control for Q-RT-PCR from microarray data
      using a block bootstrap re-sampling scheme.
AB  - BACKGROUND: The development of microarrays permits us to monitor transcriptomes
      on a genome-wide scale. To validate microarray measurements, quantitative-real
      time-reverse transcription PCR (Q-RT-PCR) is one of the most robust and commonly
      used approaches. The new challenge in gene quantification analysis is how to
      explicitly incorporate statistical estimation in such studies. In the realm of
      statistical analysis, the various available methods of the probe level
      normalization for microarray analysis may result in distinctly different target
      selections and variation in the scores for the correlation between microarray and
      Q-RT-PCR. Moreover, it remains a major challenge to identify a proper internal
      control for Q-RT-PCR when confirming microarray measurements. RESULTS: Sixty-six
      Affymetrix microarray slides using lung adenocarcinoma tissue RNAs were analyzed
      by a statistical re-sampling method in order to detect genes with minimal
      variation in gene expression. By this approach, we identified DDX5 as a novel
      internal control for Q-RT-PCR. Twenty-three genes, which were differentially
      expressed between adjacent normal and tumor samples, were selected and analyzed
      using 24 paired lung adenocarcinoma samples by Q-RT-PCR using two internal
      controls, DDX5 and GAPDH. The percentage correlation between Q-RT-PCR and
      microarray were 70% and 48% by using DDX5 and GAPDH as internal controls,
      respectively. CONCLUSION: Together, these quantification strategies for Q-RT-PCR
      data processing procedure, which focused on minimal variation, ought to
      significantly facilitate internal control evaluation and selection for Q-RT-PCR
      when corroborating microarray data.

PMID- 17540041
TI  - The evolutionary conservation of the core components necessary for the extrinsic
      apoptotic signaling pathway, in Medaka fish.
AB  - BACKGROUND: Death receptors on the cell surface and the interacting cytosolic
      molecules, adaptors and initiator caspases, are essential as core components of
      the extrinsic apoptotic signaling pathway. While the apoptotic machinery
      governing the extrinsic signaling pathway is well characterized in mammals, it is
      not fully understood in fish. RESULTS: We identified and characterized orthologs
      of mammalian Fas, FADD and caspase-8 that correspond to the death receptor,
      adaptor and initiator caspase, from the Medaka fish (Oryzias latipes). Medaka
      Fas, caspase-8 and FADD exhibited protein structures similar to that of their
      mammalian counterparts, containing a death domain (DD), a death effector domain
      (DED) or both. Functional analyses indicated that these molecules possess killing
      activity in mammalian cell lines upon overexpression or following activation by
      apoptotic stimuli, suggesting similar pro-apoptotic functions in the extrinsic
      pathway as those in mammals. Genomic sequence analysis revealed that the Medaka
      fas (tnfrsf6), fadd and caspase-8 (casp8) genes are organized in a similar
      genomic structure as the mammalian genes. Database search and phylogenetic
      analysis revealed that the fas gene, but not the fadd and casp8 genes, appear to
      be present only in vertebrates. CONCLUSION: Our results indicate that the core
      components necessary for the extrinsic apoptotic pathway are evolutionarily
      conserved in function and structure across vertebrate species. Based on these
      results, we presume the mechanism of apoptosis induction via death receptors was
      evolutionarily established during the appearance of vertebrates.

PMID- 17540042
TI  - The association of RANTES polymorphism with severe acute respiratory syndrome in
      Hong Kong and Beijing Chinese.
AB  - BACKGROUND: Chemokines play important roles in inflammation and antiviral action.
      We examined whether polymorphisms of RANTES, IP-10 and Mig affect the
      susceptibility to and outcome of severe acute respiratory syndrome (SARS).
      METHODS: We tested the polymorphisms of RANTES, IP-10 and Mig for their
      associations with SARS in 495 Hong Kong Chinese SARS patients and 578 controls.
      Then we tried to confirm the results in 356 Beijing Chinese SARS patients and 367
      controls. RESULTS: RANTES -28 G allele was associated with SARS susceptibility in
      Hong Kong Chinese (P < 0.0001, OR = 2.80, 95%CI:2.11-3.71). Individuals with
      RANTES -28 CG and GG genotypes had a 3.28-fold (95%CI:2.32-4.64) and 3.06-fold
      (95%CI:1.47-6.39) increased risk of developing SARS respectively (P < 0.0001).
      This -28 G allele conferred risk of death in a gene-dosage dependent manner (P =
      0.014) with CG and GG individuals having a 2.12-fold (95% CI: 1.11-4.06) and 4.01
      fold (95% CI: 1.30-12.4) increased risk. For the replication of RANTES data in
      Beijing Chinese, the -28 G allele was not associated with susceptibility to SARS.
      However, -28 CG (OR = 4.27, 95%CI:1.64-11.1) and GG (OR = 3.34, 95%CI:0.37-30.7)
      were associated with admission to intensive care units or death due to SARS (P =
      0.011). CONCLUSION: RANTES -28 G allele plays a role in the pathogenesis of SARS.

PMID- 17540043
TI  - The twisted pharynx phenotype in C. elegans.
AB  - BACKGROUND: The pharynx of C. elegans is an epithelial tube whose development has
      been compared to that of the embryonic heart and the kidney and hence serves as
      an interesting model for organ development. Several C. elegans mutants have been
      reported to exhibit a twisted pharynx phenotype but no careful studies have been
      made to directly address this phenomenon. In this study, the twisting mutants dig
      1, mig-4, mnm-4 and unc-61 are examined in detail and the nature of the twist is
      investigated. RESULTS: We find that the twisting phenotype worsens throughout
      larval development, that in most mutants the pharynx retains its twist when
      dissected away from the worm body, and that double mutants between mnm-4 and
      mutants with thickened pharyngeal domains (pha-2 and sma-1) have less twisting in
      these regions. We also describe the ultrastructure of pharyngeal tendinous organs
      that connect the pharyngeal basal lamina to that of the body wall, and show that
      these are pulled into a spiral orientation by twisted pharynges. Within twisted
      pharynges, actin filaments also show twisting and are longer than in controls. In
      a mini screen of adhesionmolecule mutants, we also identified one more twisting
      pharynx mutant, sax-7. CONCLUSION: Defects in pharyngeal cytoskeleton length or
      its anchor points to the extracellular matrix are proposed as the actual source
      of the twisting force. The twisted pharynx is a useful and easy-to-score
      phenotype for genes required in extracellular adhesion or organ attachment, and
      perhaps forgenes required for cytoskeleton regulation.

PMID- 17540044
TI  - Osteoblastic flare in a patient with advanced gastric cancer after treatment with
      pemetrexed and oxaliplatin: implications for response assessment with RECIST
      criteria.
AB  - BACKGROUND: The RECIST guidelines are commonly used in phase II and III clinical
      trials. The correct definition of response can be controversial in some
      situations, as in the case we describe. CASE PRESENTATION: A 43 year-old man with
      advanced gastric cancer was enrolled in a phase II trial where he was treated
      with pemetrexed 500 mg/m2 plus oxaliplatin 120 mg/m2 every 3 weeks. At baseline,
      the target lesions were lymph-nodes, and the non-target lesions were small
      pulmonary nodules. At first re-evaluation, the target lesions showed partial
      response and the non-target lesions showed complete response, but new diffuse
      osteoblastic lesions appeared. The investigator decided to continue treatment
      until the second re-evaluation. CT scan confirmed the response of the target and
      non-target lesions, while the osteoblastic lesions did not change. CONCLUSION:
      The appearance of osteoblastic lesions after an active antitumor treatment, a
      phenomenon known as flare, can complicate the definition of the best overall
      response using RECIST criteria. This possibility should be considered by
      oncologists involved in clinical trials.

PMID- 17540045
TI  - Engineering of PA-IIL lectin from Pseudomonas aeruginosa - Unravelling the role
      of the specificity loop for sugar preference.
AB  - BACKGROUND: Lectins are proteins of non-immune origin capable of binding
      saccharide structures with high specificity and affinity. Considering the high
      encoding capacity of oligosaccharides, this makes lectins important for adhesion
      and recognition. The present study is devoted to the PA-IIL lectin from
      Pseudomonas aeruginosa, an opportunistic human pathogen capable of causing lethal
      complications in cystic fibrosis patients. The lectin may play an important role
      in the process of virulence, recognizing specific saccharide structures and
      subsequently allowing the bacteria to adhere to the host cells. It displays high
      values of affinity towards monosaccharides, especially fucose--a feature caused
      by unusual binding mode, where two calcium ions participate in the interaction
      with saccharide. Investigating and understanding the nature of lectin-saccharide
      interactions holds a great potential of use in the field of drug design, namely
      the targeting and delivery of active compounds to the proper site of action.
      RESULTS: In vitro site-directed mutagenesis of the PA-IIL lectin yielded three
      single point mutants that were investigated both structurally (by X-ray
      crystallography) and functionally (by isothermal titration calorimetry). The
      mutated amino acids (22-23-24 triad) belong to the so-called specificity binding
      loop responsible for the monosaccharide specificity of the lectin. The mutation
      of the amino acids resulted in changes to the thermodynamic behaviour of the
      mutants and subsequently in their relative preference towards monosaccharides.
      Correlation of the measured data with X-ray structures provided the molecular
      basis for rationalizing the affinity changes. The mutations either prevent
      certain interactions to be formed or allow formation of new interactions--both of
      afore mentioned have strong effects on the saccharide preferences. CONCLUSION:
      Mutagenesis of amino acids forming the specificity binding loop allowed
      identification of one amino acid that is crucial for definition of the lectin
      sugar preference. Altering specificity loop amino acids causes changes in
      saccharide-binding preferences of lectins derived from PA-IIL, via creation or
      blocking possible binding interactions. This finding opens a gate towards protein
      engineering and subsequent protein design to refine the desired binding
      properties and preferences, an approach that could have strong potential for drug
      design.

PMID- 17540046
TI  - Levels of oxidative stress biomarkers in seminal plasma and their relationship
      with seminal parameters.
AB  - BACKGROUND: There is growing evidence that damage to spermatozoa by reactive
      oxygen species (ROS) play a key role in male infertility. The aim of the present
      study was to assess seminal plasma levels of total antioxidant capacity (TAC),
      free 8-Isoprostane and activities of catalase and superoxide dismutase (SOD) in
      men with asthenozoospermia, asthenoteratozoospermia and
      oligoasthenoteratozoospermia compared with normozoospermic males. METHODS: The
      patients consisted of 46 men with seminal parameters abnormalities. The patients
      were grouped into asthenozoospermic (n = 15), asthenoteratozoospermic (n = 16)
      and oligoasthenoteratozoospermic (n = 15). The control group consisted of 16
      healthy males with normozoospermia. Catalase activity was measured by Aebi
      spectrophotometeric method. Levels of TAC and SOD were measured by commercially
      available colorimetric assays. Level of free 8-Isoprostane was assessed by
      commercially available enzyme immunoassay (EIA) method. Differences between
      groups were assessed using Mann-Whitney U test and Kruskal-Wallis test.
      Coefficients of correlation were calculated using Spearman's correlation
      analysis. All hypothesis tests were two-tailed with statistical significance
      assessed at the p value < 0.05 level with 95% confidence intervals. RESULTS:
      Levels of catalase and TAC were significantly lower in patients than the control
      group. No significant changes were seen in SOD activities. Levels of free 8
      Isoprostane were significantly higher in patients than the control group.
      Furthermore, asthenozoospermic, asthenoteratozoospermic and
      oligoasthenoteratozoospermic groups had significantly lower values of catalase
      activity and TAC when compared to normozoospermic males. Levels of free 8
      Isoprostane were significantly higher in all patients subgroups than the control
      group. Levels of catalase and TAC were positively correlated with sperm motility
      and morphology. Free 8-Isoprostane levels showed an inverse correlation with
      sperm motility and morphology. CONCLUSION: Decreasing seminal plasma antioxidants
      levels, especially catalase and TAC, could have significant role in etiology of
      impaired sperm function. Measurement of 8-Isoprostane may be used as a specific
      biomarker for assessing oxidative stress on sperm.

PMID- 17540047
TI  - Aspects of early arthritis. Biological therapy in early arthritis--overtreatment
      or the way to go?
AB  - The availability of newer, and more expensive, therapies for patients with
      rheumatoid arthritis has changed treatment beyond recognition. Disease remission
      is the goal for all new patients. Studies have shown that a combination of tumour
      necrosis factor (TNF)-blocking drugs and methotrexate produces superior outcomes
      over monotherapy alone; however, use is limited by cost and potential side
      effects. Currently, anti-TNF therapy is normally reserved for patients who have
      failed traditional disease-modifying anti-rheumatic drugs. The question that
      remains is whether TNF-blocking drugs are better used if given early; the high
      direct costs are countered by both direct and indirect savings in healthcare
      costs from optimal control of disease, and the benefits of early control outweigh
      the increased risk of infection and malignancy.

PMID- 17540048
TI  - A rational route to probing membrane proteins.
AB  - A recent report describes the design of short peptides that bind specifically to
      transmembrane regions of integrins, providing an exciting tool for probing the
      biology of membrane proteins.

PMID- 17540049
TI  - Human breast cancer stem cell markers CD44 and CD24: enriching for cells with
      functional properties in mice or in man?
AB  - Identification of breast cancer stem cells as the cells within breast tumors that
      have the ability to give rise to cells that make up the bulk of the tumor mass
      has shifted the focus of cancer research. However, there is still much debate
      concerning the unique nature of the markers that distinguish cancer stem cells in
      the breast. As such, understanding whether CD44+/CD24- breast cancer cells are
      merely more successful in overcoming an engraftment incompatibility that exists
      when injecting human cells into the mouse adipose tissue or are indeed bona fide
      cancer stem cells is of great importance.

PMID- 17540051
TI  - Modelling the control strategies against dengue in Singapore.
AB  - Notified cases of dengue infections in Singapore reached historical highs in 2004
      (9459 cases) and 2005 (13,817 cases) and the reason for such an increase is still
      to be established. We apply a mathematical model for dengue infection that takes
      into account the seasonal variation in incidence, characteristic of dengue fever,
      and which mimics the 2004-2005 epidemics in Singapore. We simulated a set of
      possible control strategies and confirmed the intuitive belief that killing adult
      mosquitoes is the most effective strategy to control an ongoing epidemic. On the
      other hand, the control of immature forms was very efficient in preventing the
      resurgence of dengue epidemics. Since the control of immature forms allows the
      reduction of adulticide, it seems that the best strategy is to combine both
      adulticide and larvicide control measures during an outbreak, followed by the
      maintenance of larvicide methods after the epidemic has subsided. In addition,
      the model showed that the mixed strategy of adulticide and larvicide methods
      introduced by the government seems to be very effective in reducing the number of
      cases in the first weeks after the start of control.

PMID- 17540052
TI  - The dynamic nature of group A streptococcal epidemiology in tropical communities
      with high rates of rheumatic heart disease.
AB  - Prospective surveillance was conducted in three remote Aboriginal communities
      with high rates of rheumatic heart disease in order to investigate the
      epidemiology of group A beta-haemolytic streptococci (GAS). At each household
      visit, participants were asked about sore throat. Swabs were taken from all
      throats and any skin sores. GAS isolates were emm sequence and pattern-typed
      using standard laboratory methods. There were 531 household visits; 43 different
      emm types and subtypes (emmST) were recovered. Four epidemiological patterns were
      observed. Multiple emmST were present in the population at any one time and
      household acquisition rates were high. Household acquisition was most commonly
      via 5- to 9-year-olds. Following acquisition, there was a 1 in 5 chance of
      secondary detection in the household. Throat detection of emmST was brief,
      usually <2 months. The epidemiology of GAS in these remote Aboriginal communities
      is a highly dynamic process characterized by emmST diversity and turnover.

PMID- 17540053
TI  - Excision of the tricuspid valve in a baby with Candida endocarditis.
AB  - We report on the management of Candida endocarditis in a 5-month old infant. The
      orifice of the tricuspid valve was totally obstructed, and the tension apparatus
      of the valve destroyed. Excision of the valve led to severe failure of the right
      heart. The combined use of anti-failure treatment, and reduction of right
      ventricular afterload with oxygen, nitric oxide and sildenafil, proved
      successful.

PMID- 17540054
TI  - A 4-dimensional model of the alveolar structure.
AB  - The alveolar structure, a space-filling branching duct system with alveolar
      openings, is one of the most complicated structures in the living body. Although
      its deformation during ventilation is the basic knowledge for lung physiology,
      there has been no consensus on it because of technical difficulties of dynamic 3
      dimensional observation in vivo. It is known that the alveolar duct wall (primary
      septa) in the fetal lung is deformed so as to obtain the largest inner space and
      the widest surface area, and that the secondary septa grow just before birth and
      their free ridges form the alveolar entrance rings (mouths) containing abundant
      elastin fibers. We have constructed a 4-dimensional alveolar model according to
      this morphogenetic process, where the alveolar deformation is modeled by a
      combination of springs and hinges, corresponding to elastin fibers at alveolar
      mouths and junctions of alveolar septa, respectively. The model includes a
      hypothesis that alveolar mouths are closed at minimum volume and that closed
      alveoli are stabilized by the alveolar lining liquid film containing a
      surfactant. Morphometric characteristics of the model were consistent with
      previous reports. Furthermore, the model explained how the alveolar number and
      size could change during ventilation. Using in vivo microscopy, we validated our
      model by an analysis of the dynamic inflation and deflation of subpleural
      alveoli. Our model, including the alveolar mouth-closure hypothesis, can explain
      the origin of phase IV in a single breath nitrogen washout curve (closing volume)
      and mechanism of alveolar recruitment/derecruitment.

PMID- 17540055
TI  - No association between coding polymorphism within Exon 4 of the human surfactant
      protein B gene and pulmonary function in healthy men.
AB  - The coding polymorphism (rs1130866) within the surfactant protein B gene is known
      to associate with certain respiratory abnormalities. We investigated, using
      spirometry and fluorescence-based PCR, whether this variant influenced pulmonary
      function in healthy, nonsmoking men. We found no association of pulmonary
      function with genotype at the rs1130866 locus.

PMID- 17540056
TI  - Effect of temperature on development and survival of the parasitoid Pnigalio
      pectinicornis (Hymenoptera: Eulophidae) reared on Phyllocnistis citrella
      (Lepidoptera: Gracillariidae).
AB  - Laboratory studies were conducted to assess the effect of temperature on the
      development and survival of the indigenous parasitoid Pnigalio pectinicornis L.
      on the citrus leaf miner Phyllocnistis citrella Stainton as host, fed on leaves
      of Citrus sinensis L. Osbck cultivar Washington navel and Citrus reticulata
      Blanco cultivar Clementine. Experiments were conducted at five constant
      temperatures ranging from 15 to 32.5 degrees C, with 60 +/- 10% RH and a
      photoperiod of 14:10 (L:D) h. The relationship between the developmental rate and
      temperature was determined using both linear and nonlinear (Lactin's formula)
      models. Developmental time of immature stages tended to be shorter as the
      temperature increased the range from 15 to 30 degrees C. Mortality was greater at
      the temperatures extreme tested. Both linear and nonlinear models provided a
      reliable fit of developmental rates versus temperature for all immature stages.
      Developmental thresholds that were estimated by the linear model for eggs were
      higher than those estimated by the nonlinear model. However, higher values of the
      low developmental threshold for larva and pupa stage of P. pectinicornis were
      estimated by the Lactin-2 model than that by the linear model. The potential of
      these models to predict the phenology of this parasitoid and its biological
      characteristics found in this study are discussed for its proper use as a
      biological control agent.

PMID- 17540057
TI  - Trend of temephos resistance in Aedes (Stegomyia) mosquitoes in Thailand during
      2003-2005.
AB  - The diagnostic dose for temephos susceptibility test was established based on
      Aedes aegypti, the susceptible Bora (French Polynesia) strain, for practical and
      routine use. The diagnostic dose was subsequently used to evaluate the
      susceptibility/resistance status in F1 progenies of field-collected samples from
      Bangkok and various parts of Thailand. It appeared that Ae. aegypti mosquitoes of
      one collection site each in Bangkok, Nakhon Sawan (northcentral), and Nakhon
      Ratchasrima (northeast) were resistant to temephos, with mortality ranging from
      50.5 to 71.4%. Moreover, there was a trend of resistance to temephos among Ae.
      aegypti populations of all studied districts of Nakorn Ratchasima and most areas
      of Nakhon Sawan, of which those in one area were susceptible. However, various
      levels of temephos susceptibility were found in Bangkok populations, including
      resistance and incipient resistance. In Chonburi Province (eastern), all
      mosquitoes were susceptible to temephos with an indication of tolerance in one
      sample. Additionally, mosquitoes from Songkhla (south), Chiang Rai (north),
      Kanchanaburi (west), and Chanthaburi (east) remained susceptible to temephos
      during the sample collecting period. Bioassay tests on Aedes albopictus
      populations collected in this study from Nakhon Sawan, Nakorn Ratchasima,
      Songkhla, and Kanchanaburi revealed high susceptibility to temephos. Although the
      use of temephos seems to be potentially effective in many areas of the country, a
      noticeable trend of resistance indicated that alternative vector control methods
      should be periodically applied.

PMID- 17540058
TI  - Influence of soil texture, moisture, and surface cracks on the performance of a
      root-feeding flea beetle, Longitarsus bethae (Coleoptera: Chrysomelidae), a
      biological control agent for Lantana camara (Verbenaceae).
AB  - Laboratory studies were conducted to determine the influence of soil texture,
      moisture and surface cracks on adult preference and survival of the root-feeding
      flea beetle, Longitarsus bethae Savini and Escalona (Coleoptera: Chrysomelidae),
      a natural enemy of the weed, Lantana camara L. (Verbenaceae). Adult feeding,
      oviposition preference, and survival of the immature stages of L. bethae were
      examined at four soil textures (clayey, silty loam, sandy loam, and sandy soil),
      three soil moisture levels (low, moderate, and high), and two soil surface
      conditions (with or without surface cracks). Both soil texture and moisture had
      no influence on leaf feeding and colonization by adult L. bethae. Soil texture
      had a significant influence on oviposition, with adults preferring to lay on
      clayey and sandy soils to silty or sandy loam soils. However, survival to
      adulthood was significantly higher in clayey soils than in other soil textures.
      There was a tendency for females to deposit more eggs at greater depth in both
      clayey and sandy soils than in other soil textures. Although oviposition
      preference and depth of oviposition were not influenced by soil moisture,
      survival in moderately moist soils was significantly higher than in other
      moisture levels. Development of immature stages in high soil moisture levels was
      significantly slower than in other soil moisture levels. There were no variations
      in the body size of beetles that emerged from different soil textures and
      moisture levels. Females laid almost three times more eggs on cracked than on
      noncracked soils. It is predicted that clayey and moderately moist soils will
      favor the survival of L. bethae, and under these conditions, damage to the roots
      is likely to be high. This information will aid in the selection of suitable
      release sites where L. bethae would be most likely to become established.

PMID- 17540059
TI  - Life history traits of Pseudasphondylia rokuharensis (Diptera: Cecidomyiidae)
      affecting emergence of adults and synchronization with host plant phenology.
AB  - To identify adaptive strategies of gall-inducing cecidomyiids, we studied the
      life history traits of Pseudasphondylia rokuharensis (Diptera: Cecidomyiidae), a
      univoltine species inducing fruit galls on a deciduous shrub, Viburnum dilatatum.
      Although univoltine gall midges that are associated with trees or shrubs are
      usually difficult to rear from immature stages under artificial conditions, we
      successfully reared P. rokuharensis from first instar to adult. Mature larvae
      entered diapause in autumn, and the diapause terminated after low temperature
      treatment (4 mo of incubation at 5 degrees C). The adults emerged within a
      shorter period of time than those without low temperature treatment. Thus, the
      diapause provides better synchronization of adult emergence in the spring.
      Because adults live for only a few days, this synchronization improves the
      chances of adults finding a mate. This is the first report on the mechanism of
      larval diapause termination for univoltine and tree- or shrub-associated gall
      midges. The numbers of days needed for adults to emerge under laboratory
      conditions after low temperature incubation were significantly different between
      two different localities. This result might suggest the possible existence of
      ecoclines in their life history parameters.

PMID- 17540060
TI  - Physiology complements population structure of two endemic log-dwelling beetles.
AB  - Given rapid, global land modification and the likelihood of major global climate
      changes, it is becoming increasingly important to understand the physiological
      limits and capabilities of species to allow more accurate prediction of species'
      distributions under different scenarios of climate and landscape management. We
      studied whether the different habitat requirements of two species of tenebrionid
      beetles in temperate eucalypt forest could explain their patterns of dispersal
      and gene flow by applying flow-through respirometry to analysis of their
      physiological responses to different, ecologically relevant temperatures. Both
      Adelium calosomoides and Apasis puncticeps showed sensitivity to increasing
      temperatures (in terms of water loss), but Ap. puncticeps lost more water per
      unit of CO2 produced than did Ad. calosomoides. Recovery time from chill coma was
      also significantly longer for Ap. puncticeps than Ad. calosomoides. This
      supported prior qualitative assessment that Ap. puncticeps is more of a habitat
      specialist than Ad. calosomoides, at least concerning the critical factor of
      moisture requirements, and is consistent with stronger population genetic
      patterning and inferred low mobility of Ap. puncticeps. Despite its relatively
      lower mobility as deduced from population genetic structure, Ap. puncticeps
      walked four times faster than Ad. calosomoides in a laboratory assay, indicating
      that, for these species, mobility and gene flow are influenced more by
      physiological limitations than by speed.

PMID- 17540061
TI  - Diapause in the leaf beetle Diorhabda elongata (Coleoptera: Chrysomelidae), a
      biological control agent for tamarisk (Tamarix spp.).
AB  - The tamarisk leaf beetle, Diorhabda elongata Brulle deserticola Chen, was
      collected in northwestern China and has been released in the western United
      States to control tamarisk (Tamarix spp.). Characteristics of diapause and
      reproductive development in D. elongata were examined to improve management as a
      biocontrol agent. Under long days, 16:8 (L:D) h, males began to emit aggregation
      pheromone within 2-3 d of adult emergence, mating occurred, and females
      oviposited within 7 d of adult emergence. Under short days, 12:12 (L:D) h, males
      did not emit pheromone, mating did not occur, and both males and females entered
      reproductive diapause marked by inconspicuous gonads and hypertrophied fat body.
      Ovaries of diapausing females lacked vitellogenic oocytes, and the ovarioles were
      clear and narrow, whereas reproductive females had enlarged ovaries with two to
      three yellow oocytes per ovariole. Diapausing males had thin, transparent
      accessory glands and ejaculatory ducts, whereas reproductive males had thick
      white accessory glands and white opaque ejaculatory ducts. Sensitivity to
      diapause-inducing photoperiods extended into the adult stage. Reproductive
      females ceased oviposition, resorbed oocytes, and entered diapause when switched
      from long to short days. Diapause-destined insects ceased feeding and entered the
      leaf litter 10-20 d after adult emergence, whereas reproductive insects remained
      on the plants and fed for at least 30 d. Reproductive insects exhibited dispersal
      behaviors, such as attempted flights, whereas diapause-destined insects did not
      show dispersal behaviors. Information gained from these studies will be used to
      better manage populations in the field and to improve rearing and storage in the
      laboratory.

PMID- 17540062
TI  - Decline of soybean aphid (Homoptera: Aphididae) egg populations from autumn to
      spring on the primary host, Rhamnus cathartica.
AB  - Soybean aphid, Aphis glycines Matsumura (Homoptera: Aphididae), is a severe pest
      of soybeans in North America. Soybean aphid populations cycle between a secondary
      summer host, where populations reproduce parthenogenetically and a primary host,
      where populations overwinter as eggs. In North America, the secondary host is
      soybean, and the primary hosts are Rhamnus cathartica L. (Rhamnaceae) and R.
      alnifolia L'Her. A location with abundant populations of soybean aphid on R.
      cathartica was identified near Guelph, Ontario, Canada, in October 2004, and eggs
      on trees were counted at multiple sites within that location each autumn and
      spring over the next 2 yr. Dynamics of naturally occurring soybean aphid
      populations on the primary host were assessed with respect to (1) decline of
      overwintering eggs from autumn to spring, (2) development of spring populations
      on R. cathartica, and (3) development of soybean aphid populations on soybean
      immediately adjacent to overwintering sites. Counts of aphid eggs declined by
      approximately 70% between autumn and spring sampling periods in 2004-2005.
      Significant differences in counts of aphid eggs relative to sampling height were
      observed in the canopy of R. cathartica. No edge effects were observed in the
      development of soybean aphid populations in soybeans adjacent to overwintering
      sites in this study. Very few eggs were collected at the same study location in
      the autumn of 2005, and no aphid eggs were collected from samples taken in the
      spring of 2006. Egg counts taken in the autumn of 2006 were intermediate in
      number relative to counts taken in the autumn of 2004 and 2005.

PMID- 17540063
TI  - Resurgence and persistence of Dorymyrmex flavus after reduction of Solenopsis
      invicta buren with a broadcast bait.
AB  - The effects of bait treatment(s) on population dynamics of Solenopsis invicta and
      Dorymyrmex flavus were studied, and various factors underlying the resurgence and
      persistence of D. flavus to reinvasion by S. invicta were studied in more detail.
      Pitfall traps, bait vials, transect sampling, and direct inspections were used to
      monitor densities of these two species, and inspections of D. flavus midden
      contents, video monitoring of D. flavus colonies, and studies of the fate of
      marked S. invicta were used to further clarify interactions of these two species,
      D. flavus abundance increased after the reduction of S. invicta with baits. D.
      flavus was also observed to sustain higher densities for an extended period (2
      yr) after cessation of bait treatment and to exhibit antagonistic behaviors
      toward S. invicta, showing an ability to resist reinvasion of the treated area by
      S. invicta. Given these findings, D. flavus may retard domination of the ant
      assemblage by S. invicta. Additional studies are justified regarding how to
      enhance the role of this species in affected ecosystems.

PMID- 17540064
TI  - Importance of dung incorporation activity by three species of coprophagous beetle
      (Coleoptera: Scarabaeidae: Scarabaeinae) macrofauna in pastureland on "La
      Michilia" biosphere reserve in Durango, Mexico.
AB  - The dung incorporation activity of three species of coprophagous beetle
      macrofauna (Coleoptera: Scarabaeidae: Scarabaeinae), Dichotomius colonicus (Say),
      Phanaeus quadridens (Say), and Copris klugi sierrensis Matthews, was studied on a
      hectare of pastureland on "La Michilia" Biosphere Reserve. In total, 223
      specimens of the three species were recorded. On the basis of abundance, the
      dominant species was D. colonicus. A substantial percentage (31% in September and
      51% in October) of dung pats remained on the surface, untouched by beetles. Most
      of the specimens observed (92%) were found amassing dung in galleries. The dung
      accumulation capacity of D. colonicus varied from 5 to 135 g of dung (dry
      weight)/pair, whereas C. klugi sierrensis amassed an average of 24.3 +/- 8.5
      g/pair and P. quadridens amassed an average of 12 +/- 2.5 g/pair. Based on dung
      burying efficiency, D. colonicus was considered the most beneficial of the three
      species in the study area. It dug deeper, wider galleries and incorporated the
      largest amount of dung into the soil.

PMID- 17540065
TI  - Diversity of Carabidae (Insecta, Coleoptera) in epiphytic Bromeliaceae in central
      Veracruz, Mexico.
AB  - This paper documents the existence of carabid assemblages associated with
      bromeliads on the Cofre de Perote, Veracruz, Mexico. Based on bromeliads sampled
      over three altitudinal ranges, the assemblages included at least 26 species with
      an arboreal lifestyle and another 11 species that are not strictly arboreal.
      Seven species are new to science, urging us to pay attention to the arboreal
      fauna in forest conservation studies. Composition of carabid assemblages
      associated with bromeliads changes with altitude. In lowlands, it is comprised
      almost entirely of species of Lebiini, with the Platynini dominating assemblages
      found in bromeliads >1,000 m above sea level. Our data suggest that carabids use
      bromeliads to reduce stresses associated with drought periods, the exact timing
      of which depends on altitude. The unexpected low diversity of the carabid fauna
      associated with bromeliads at middle altitude is explained in terms of
      anthropogenic conversion of the original forest to pastureland. Given the
      importance of arboreal elements, further fragmentation of subtropical and
      tropical mountain forest significantly threatens overall carabid diversity.

PMID- 17540066
TI  - Initial impacts and field validation of host range for Boreioglycaspis melaleucae
      Moore (Hemiptera: Psyllidae), a biological control agent of the invasive tree
      Melaleuca quinquenervia (Cav.) Blake (Myrtales: Myrtaceae: Leptospermoideae).
AB  - Invasion of south Florida wetlands by the Australian paperbark tree, Melaleuca
      quinquenervia (Cav.) S.T. Blake (melaleuca), has caused adverse economic and
      environmental impacts. The tree's biological attributes and favorable ambient
      biophysical conditions combine to complicate efforts to restore and maintain
      south Florida ecosystems. Management requires an integrated strategy that deploys
      multiple biological control agents to forestall reinvasion and to supplement
      other control methods, thereby lessening recruitment and regeneration after
      removal of existing trees. This biological control program began during 1997 when
      an Australian weevil, Oxyops vitiosa (Pascoe), was released. A second Australian
      insect, the melaleuca psyllid (Boreioglycaspis melaleucae Moore), first
      introduced during 2002, has also widely established. After inoculation of the
      psyllid in a field study, only 40% of seedlings survived herbivory treatments
      compared with 95% survival in controls. The resultant defoliation also reduced
      growth of the surviving seedlings. A weevil-induced decline at a site comprised
      mainly of coppicing stumps had slowed after a 70% reduction. Psyllids colonized
      the site, and 37% of the remaining coppices succumbed within 10 mo. The realized
      ecological host range of B. melaleucae was restricted to M. quinquenervia; 18
      other nontarget plant species predicted to be suboptimal or nonhosts during
      laboratory host range testing were unaffected when interspersed with psyllid
      infested melaleuca trees in a common garden study. Evaluations are ongoing, but
      B. melaleucae is clearly reducing seedling recruitment and stump regrowth without
      adversely impacting other plant species. Manifestation of impacts on mature trees
      will require more time, but initial indications suggest that the psyllid will be
      an effective supplement to the weevil.

PMID- 17540067
TI  - Oviposition response of green lacewings (Neuroptera: Chrysopidae) to aphids
      (Hemiptera: Aphididae) and potential attractants on pecan.
AB  - Pecan foliage is attacked by three species of aphids [Monellia caryella (Fitch),
      Melanocallis caryaefoliae (Davis), and Monelliopsis pecanis Bissell], resulting
      in damage that can reduce tree nut yield. In this study, we assayed the
      ovipositional response of the green lacewing Chrysoperla rufilabris (Burmeister)
      to M. caryella and M. caryaefoliae at high and low aphid densities and the
      development of C. rufilabris larvae when fed solely on each of the three pecan
      aphid species. During 2004 and 2005, combinations of attractants and food sprays
      were applied to pecan trees in an orchard to monitor green lacewing ovipositional
      response. We found that C. rufilabris laid more eggs on seedling trees infested
      with the M. caryella (at both high and low densities) than on seedlings infested
      with M. caryaefoliae. Development of C. rufilabris was unaffected by aphid
      species. At least one attractant/food spray treatment applied to trees in an
      orchard significantly increased green lacewing oviposition for three of the five
      treatment dates over both years. These results show that larvae of C. rufilabris
      will consume all aphid species attacking pecan, even though female ovipositional
      response can differ for aphid species. It is likely that combinations of
      attractants and food sprays can be used to enhance green lacewing populations in
      orchards.

PMID- 17540068
TI  - Sticky traps for monitoring Pseudacteon parasitoids of Solenopsis fire ants.
AB  - A newly developed method for passively trapping adult Pseudacteon phorid flies,
      which parasitize workers of Solenopsis saevissima complex fire ants, is
      described. Adult flies responding to deployed Solenopsis invicta midden were
      captured when they landed on a Tanglefoot-coated perch, which is part of the
      trap. This sampling method provided a uniform, repeatable, and verifiable sample
      that allowed continuous and simultaneous sampling among locations, which can only
      be accomplished with other techniques by substantially increasing the number of
      observers. A field test showed the superior operational efficiency and
      effectiveness of this method relative to other techniques. These traps have been
      shown effective in various phorid habitats in Texas and Florida. We expect this
      trap to also be effective in detecting/monitoring phorid flies in other
      locations.

PMID- 17540069
TI  - Optimization of sampling methods for within-tree populations of red oak borer,
      Enaphalodes rufulus (Haldeman) (Coleoptera: Cerambycidae).
AB  - In the Ozark Mountains of northern Arkansas and southern Missouri, an oak decline
      event, coupled with epidemic populations of red oak borer (Enaphalodes rufulus
      Haldeman), has resulted in extensive red oak (Quercus spp., section Lobatae)
      mortality. Twenty-four northern red oak trees, Quercus rubra L., infested with
      red oak borer, were felled in the Ozark National Forest between March 2002 and
      June 2003. Infested tree boles were cut into 0.5-m sample bolts, and the
      following red oak borer population variables were measured: current generation
      galleries, live red oak borer, emergence holes, and previous generation
      galleries. Population density estimates from sampling plans using varying numbers
      of samples taken randomly and systematically were compared with total census
      measurements for the entire infested tree bole. Systematic sampling consistently
      yielded lower percent root mean square error (%RMSE) than random sampling.
      Systematic sampling of one half of the tree (every other 0.5-m sample along the
      tree bole) yielded the lowest values. Estimates from plans systematically
      sampling one half the tree and systematic proportional sampling using seven or
      nine samples did not differ significantly from each other and were within 25%
      RMSE of the "true" mean. Thus, we recommend systematically removing and
      dissecting seven 0.5-m samples from infested trees as an optimal sampling plan
      for monitoring red oak borer within-tree population densities. This optimal
      sampling plan should allow for collection of acceptably accurate within-tree
      population density data for this native wood-boring insect and reducing labor and
      costs of dissecting whole trees.

PMID- 17540070
TI  - Effects of induced water stress on leaf trichome density and foliar nutrients of
      three elm (Ulmus) species: implications for resistance to the elm leaf beetle.
AB  - Seedlings of three elm species with variable susceptibility to the elm leaf
      beetle (Pyrrhalta luteola Muller) (Coleoptera: Chrysomelidae) were subjected to
      three water stress treatments (no stress, low stress, and high stress) in a
      greenhouse experiment. The species tested were Ulmus pumila L. (Siberian elm =
      highly susceptible), U. parvifolia Jacq. (Chinese elm = resistant), and U.
      americana L. (American elm = intermediate). The seedlings were analyzed for
      changes in the levels of selected host traits (trichome density, foliar
      concentration of nitrogen [N], phosphorus [P], potassium [K], calcium [Ca],
      magnesium [Mg], iron [Fe], and manganese [Mn]), some of which had previously been
      implicated in resistance to the elm leaf beetle. Density of leaf abaxial surface
      trichomes (simple, bulbous, and total trichomes) and foliar Fe and Mg
      concentrations increased significantly in the highly susceptible Siberian elms
      under water stress. In contrast, stress reduced trichome density in the
      moderately susceptible American elms, but it had no effect on levels of foliar
      mineral nutrients. The stress treatments had no influence on host traits in the
      resistant Chinese elms. The results suggest that environmental stress can alter
      plant traits that are likely involved in determining resistance of elms to the
      elm leaf beetle.

PMID- 17540071
TI  - Photosynthetic responses of wheat, Triticum aestivum L., to defoliation patterns
      on individual leaves.
AB  - The impact of defoliation by fall armyworm, Spodoptera frugiperda (J. E. Smith),
      on the photosynthetic rates of injured, individual wheat, Triticum aestivum L.,
      leaves and the impact of different spatial patterns of artificial insect
      defoliation on photosynthesis of remaining leaf tissue of injured, individual
      wheat leaves were evaluated in this study. Photosynthesis, stomatal conductance,
      transpiration, and chlorophyll a fluorescence were recorded in the flag-leaves of
      wheat plants 1 and 24 h after defoliation in 2003 and at 1 h, 24 h, 7 d, and 14 d
      after defoliation in 2004. Photosynthesis of injured leaves was not significantly
      affected by any defoliation treatment (i.e., control, natural, and artificial).
      Similarly, we did not observe interactions between defoliation treatments and
      time after defoliation. Stomatal conductance was significantly affected by time
      after defoliation and by the interaction between defoliation treatment and time
      after defoliation. However, in general, our results showed that wheat responded
      similarly to insect defoliation and artificial defoliation, which, therefore, may
      be used to simulate leaf mass consumption. Spatial defoliation patterns had a
      significant effect on photosynthetic parameters of injured leaves, but responses
      were dependent on plant developmental stages. The chlorophyll a fluorescence data
      revealed no significant effects from any defoliation pattern on the photochemical
      efficiency of the injured leaf. No significant interactions between defoliation
      patterns and time after defoliation were observed. Our findings reveal that the
      spatial pattern of defoliation in wheat affects photosynthetic and other gas
      exchange responses, which suggests that when simulating insect defoliation in
      wheat, researchers need to be cognizant of the defoliation pattern to adequately
      simulate insect defoliation.

PMID- 17540072
TI  - Foliage of oaks grown under elevated CO2 reduces performance of Antheraea
      polyphemus (Lepidoptera: Saturniidae).
AB  - To understand how the increase in atmospheric CO2 from human activity may affect
      leaf damage by forest insects, we examined host plant preference and larval
      performance of a generalist herbivore, Antheraea polyphemus Cram., that consumed
      foliage developed under ambient or elevated CO2. Larvae were fed leaves from
      Quercus alba L. and Quercus velutina Lam. grown under ambient or plus 200
      microl/liter CO2 using free air carbon dioxide enrichment (FACE). Lower
      digestibility of foliage, greater protein precipitation capacity in frass, and
      lower nitrogen concentration of larvae indicate that growth under elevated CO2
      reduced the food quality of oak leaves for caterpillars. Consuming leaves of
      either oak species grown under elevated CO2 slowed the rate of development of A.
      polyphemus larvae. When given a choice, A. polyphemus larvae preferred Q.
      velutina leaves grown under ambient CO2; feeding on foliage of this species grown
      under elevated CO2 led to reduced consumption, slower growth, and greater
      mortality. Larvae compensated for the lower digestibility of Q. alba leaves grown
      under elevated CO2 by increasing the efficiency of conversion of ingested food
      into larval mass. Despite equivalent consumption rates, larvae grew larger when
      they consumed Q. alba leaves grown under elevated compared with ambient CO2.
      Reduced consumption, slower growth rates, and increased mortality of insect
      larvae may explain lower total leaf damage observed previously in plots in this
      forest exposed to elevated CO2. By subtly altering aspects of leaf chemistry, the
      ever-increasing concentration of CO2 in the atmosphere will change the trophic
      dynamics in forest ecosystems.

PMID- 17540073
TI  - Willow regrowth after galling increases bud production through increased shoot
      survival.
AB  - Insect herbivory can negatively or positively affect plant performance. We
      examined how a stem gall midge Rabdophaga rigidae affects the survival, growth,
      and bud production of current year shoots of the willow Salix eriocarpa. In mid
      May, the gall midge initiates stem galls on the apical regions of shoots. The
      following spring, galled shoots had thicker basal diameters and more lateral
      shoots than ungalled shoots. Although galled shoots were on average 1.6 times
      longer than ungalled shoots, there were no significant differences in shoot
      length or in the numbers of reproductive, vegetative, and dormant buds per shoot.
      However, the subsequent survival of galled shoots was significantly higher than
      that of ungalled shoots, probably because of the thicker basal diameter. This
      increased shoot survival resulted in approximately two times greater
      reproductive, vegetative, and dormant bud production on galled shoots compared
      with ungalled shoots in the following spring. These results suggest that the
      willow regrowth induced by galling can lead to an increase in bud production
      through increased shoot survival.

PMID- 17540074
TI  - Friend or foe?: a plant's induced response to an omnivore.
AB  - Omnivorous natural enemies of herbivores consume plant-based resources and may
      elicit induced resistance in their host plant. A greater induction threshold for
      damage produced by omnivorous predators than for strict herbivores might be
      expected if omnivore performance is enhanced on noninduced plants, allowing them
      to reduce future levels of herbivory. Currently, it is not known if a plant
      responds to feeding by omnivorous predators and by herbivores similarly. To
      examine this question, we chose herbivore and omnivore species that produce the
      same kind of quantifiable damage to cotton leaves, enabling us to control
      statistically for the intensity of plant damage, and ask whether plant responses
      differed depending on the identity of the damaging species. We first compared
      changes in plant peroxidase activity, gossypol gland number and density, and leaf
      area in response to feeding by the spider mite Tetranychus turkestani (Ugarov and
      Nikolski) (an herbivore) and by one of the mite's principal natural enemies, the
      western flower thrips Frankliniella occidentalis (Pergande) (an omnivore). Both
      species increased the activity of peroxidase, but when we controlled for the
      amount of damage, the peroxidase activity of mite-damaged plants was higher than
      that of thrips-damaged plants. We also found that thrips, but not spider mites,
      increased the density of gossypol glands in the second true leaf. In a second
      experiment we included an additional herbivore, the bean thrips Caliothrips
      fasciatus (Pergande), to see if the different responses of cotton to thrips and
      mite herbivory we first observed were attributable to differences in trophic
      function (herbivore versus omnivore) or to other differences in feeding generated
      by thrips versus mites. Cotton plants exhibited the same pattern of induced
      responses (elevated peroxidase, increased number of glands, reduced leaf area) to
      herbivory generated by the bean thrips (an herbivore) and western flower thrips
      (an omnivore), suggesting that trophic function was not a key determinant of
      plant response. Thrips-damaged plants again showed a significantly higher density
      of gossypol glands than did mite-damaged plants. Overall, our results suggest
      that (1) an omnivorous predator systemically induces resistance traits in cotton
      and (2) whereas there is evidence of taxonomic specificity (thrips versus mites),
      there is little support for trophic specificity (herbivorous thrips versus
      omnivorous thrips) in the elicitation of induced responses.

PMID- 17540075
TI  - Monarch butterfly oviposition on swallow-worts (Vincetoxicum spp.).
AB  - As black swallow-wort, Vincetoxicum nigrum L. Moench, and pale swallow-wort, V.
      rossicum (Kleopow) Barbar., spread throughout the northeastern United States and
      southern Canada, there is concern about the impact of these invasive plants on
      populations of the native North American monarch butterfly Danaus plexippus L.
      Recent laboratory studies in New York and Ontario, Canada, have found little or
      no oviposition by monarch butterflies on the two Vincetoxicum species. In Rhode
      Island, we found 10.5-21.7% oviposition on Vincetoxicum species relative to
      common milkweed Asclepias syriaca L. in choice tests and 11.9-20.3% in no-choice
      tests in 2 yr of laboratory testing. These results were supported by field cage
      trials where monarchs given a choice between V. nigrum and A. syriaca laid 24.5%
      of their eggs on V. nigrum. In surveys of three pasture fields in Rhode Island
      where relative coverage of A. syriaca exceeded that of V. nigrum by a 0.77:0.23
      ratio, 15.4% of monarch eggs were found on V. nigrum plants. In V. nigrum stands
      with very little A. syriaca (6.25 stems/ha), monarch egg density on V. nigrum was
      found to be over five times greater than in the three mixed pasture fields. In
      none of our laboratory or field evaluations was there any survival of monarch
      larvae on Vincetoxicum species. It seems that in Rhode Island, Vincetoxicum
      species serve as an oviposition sink for monarch butterflies. These findings
      suggest that East Coast butterflies may differ in host selection from those in
      central New York and southern Ontario, Canada.

PMID- 17540076
TI  - Genetic diversity in laboratory colonies of western corn rootworm (Coleoptera:
      Chrysomelidae), including a nondiapause colony.
AB  - Laboratory-reared western corn rootworms, Diabrotica virgifera virgifera, from
      colonies maintained at the North Central Agricultural Research Laboratory (NCARL)
      in Brookings, SD, are used extensively by many researchers in studies of the
      biology, ecology, behavior, and genetics of this major insect pest. A nondiapause
      colony developed through artificial selection in the early 1970s is particularly
      attractive for many studies because its generation time is much shorter than that
      of typical diapause colonies. However, the nondiapause colony has been in culture
      for approximately 190 generations without out-crossing. We compared variation at
      six microsatellite loci among individuals from the NCARL nondiapause colony
      (approximately 190 generations), main diapause colony (approximately 22
      generations), four regional diapause colonies (3-8 generations), and four wild
      populations. Genetic diversity was very similar among the diapause laboratory
      colonies and wild populations. However, the nondiapause colony showed
      approximately 15-39% loss of diversity depending on the measure. Pairwise
      estimates of F(ST) were very low, revealing little genetic differentiation among
      laboratory colonies and natural populations. The nondiapause colony showed the
      greatest genetic differentiation with an average pairwise F(ST) of 0.153. There
      was little evidence that the laboratory colonies had undergone genetic
      bottlenecks except for the nondiapause colony. The nondiapause colony has
      suffered a moderate loss in genetic diversity and is somewhat differentiated from
      wild populations. This was not unexpected given its history of artificial
      selection for the nondiapause trait, and the large number of generations in
      culture. In contrast, the results indicate that the diapause colonies maintained
      at NCARL are genetically similar to wild populations.

PMID- 17540077
TI  - Arthropod abundance and diversity in Bt and non-Bt rice fields.
AB  - In a field experiment, possible effects of transgenic Bt rice on arthropod
      communities under paddy field conditions were assessed for 3 yr in terms of
      arthropod guild dominance, family composition, dominance distribution of each
      guild, individuals of each guild, and community indices (including Shannon-Weaver
      diversity index and dominant concentration index). Our results overall suggested
      no significant differences between the Bt and control rice plots in these
      arthropod community-specific parameters. The similarity of arthropod communities
      in the Bt and control rice plots was apparently high. Based on our findings, we
      conclude that Bt rice generally exerts no marked negative effects on the
      arthropod community in paddy fields.

PMID- 17540080
TI  - Cervical cancer in developing countries: how can we reduce the burden? Awareness
      raising, screening, treatment and palliation.
AB  - Cervical cancer is an important health problem in developing countries. Most
      women present with advanced disease, resulting in low cure rates. Screening by
      Visual Inspection with the Aid of Acetic Acid and optionally HPV DNA detection as
      a second test is technically feasible. However, the majority of women appear to
      be reluctant to attend a screening clinic. This is probably due to lack of
      knowledge and a low priority of women's health in local communities. There is an
      obvious need to obtain more knowledge on communities' perceptions and
      understanding of cervical cancer. Furthermore, we need more information on what
      issues should be addressed in order to perform cervical cancer screening in an
      acceptable manner. Treatment of cervical cancer in developing countries is highly
      dependent on the resources and skills available. Efforts to provide adequate
      palliation should be enhanced as relief of troublesome symptoms can often be
      achieved by relatively simple and low-cost measures.

PMID- 17540081
TI  - The use of ultrasonography in obstetrics in developing countries.
AB  - Ultrasonography in pregnancy is one of the most important advances in antenatal
      and obstetric emergency care. The benefits of diagnostic ultrasound in a resource
      poor setting are well known and undisputed. Routine ultrasound can provide real
      benefit to patients when it is included in antenatal care programmes designed to
      improve maternal and neonatal health, and it should become a standard procedure
      in developing countries. Proper training of the antenatal ultrasound imager is
      very important. This should include training in ethics, use and misuse of
      ultrasonography as well as good technique and understanding of implications for
      clinical care to improve sensitivity. Training should be aimed not only at
      doctors but also at midwives who conduct most of the antenatal care and skilled
      deliveries in developing countries. Communication with patients and information
      about the limitations and benefits of ultrasound are essential to alleviate fear
      and to discourage irrational expectation and demand. Finally, routine antenatal
      ultrasound should be monitored closely for possible misuse, such as sex screening
      and selective abortion of normal female fetuses, and non-indicated overuse by
      health-care professionals for their own financial benefits.

PMID- 17540082
TI  - Downstaging for cervical cancer: a community-based study in the rural areas of
      Udupi district, Karnataka, India.
AB  - The objective of this study is to determine the feasibility of utilizing trained
      auxiliary nurse midwives (ANMs) in downstaging for cancer cervix in a rural area.
      The study population included all married women in the age group of 35-59 years
      in two villages of the field practice area. It was a cross-sectional study. Two
      ANMs were trained in history taking, visual inspection of the cervix, using of
      speculum and collecting Papanicolaou smears. After training, they made home
      visits and identified women with gynaecological symptoms suggestive of cervical
      cancer. These women were asked to report to Rural Maternity and Child Welfare
      whom homes where the ANMs did a visual inspection of the cervix and made a
      cervical smear. A total of 1402 women were registered of the ANMs could identify
      368 women (26%) with symptoms. Only 192 (52.2%) of these women reported for
      examination. Chronic cervicitis accounted for the largest proportion of the cases
      (44.8%). In all, three cases were diagnosed as suspected cases of cancer cervix.
      On cytology, three cases (1.5%) turned out to be malignant. When clinical
      findings of the ANM were compared with results of cytological examination, a high
      degree of sensitivity (78.4%) and positive predictive value (97.1%) were observed
      in diagnosing abnormal cytological findings. However, the sensitivity for
      detecting specific conditions was generally low. Sensitivity for detecting
      erosion was 45%, for chronic cervicitis 30%, and malignancies were totally
      missed. In conclusion, this study clearly shows that ANMs, if trained, would be
      capable of identifying symptomatic women, differentiating a normal cervix from an
      abnormal one and taking an adequate smear for cytological examination.

PMID- 17540083
TI  - Care takers' recall of Integrated Management of Childhood Illness counselling
      messages in Benin.
AB  - A key goal of the Integrated Management of Childhood Illness (IMCI) strategy is
      to improve the management of childhood illness at health facilities.
      IMCIguidelines contain many counselling messages, and as it is not known how well
      caretakers recall these messages, we studied caretakers' recall of IMCI messages
      when given under ideal conditions. At a clinic in Benin, a study clinician
      performed counselling and confirmed caretakers'comprehension of all messages.
      Caretakers were randomly assigned to be interviewed either immediately after the
      consultation or a day later. Recall was assessed with general and focused open
      ended questions. Recall was assessed for 55 caretakers, 29.1% of whom were
      literate. Caretakers received 3-75 messages (mean = 38.7). The mean percentage of
      messages recalled was 89.7% immediately after the consultation and 81.9% one day
      later. These results support IMCI's recommendation that health workers should
      verify caretakers' comprehension by asking caretakers to repeat counselling
      messages during consultations.

PMID- 17540084
TI  - Obstetric complications, intervention rates and maternofetal outcome in teenage
      nullipara in Benin City, Nigeria.
AB  - An audit to determine the incidence of births to teenage nullipara, pregnancy
      complications, obstetric intervention rates, maternal and fetal outcomes in 114
      teenage nullipara compared with 700 randomly selected older nullipara (age 20-29
      years), was undertaken in a tertiary Institution. Births to teenage nullipara
      contributed 1.7% of all deliveries. Teenagers were significantly more likely to
      be unbooked for antenatal care (P < 0.0001), book late (P < 0.0001) and be single
      mothers (P < 0.0001). Teenagers were also significantly more likely to have
      primary education (P < 0.0001), secondary education (P < 0.001) or be apprentices
      (P < 0.0001). Teenagers had a significantly higher incidence of caesarean
      sections (P = 0.0002). There were no significant differences in the incidence of
      pregnancy complications, induction or augmentation of labour, preterm delivery,
      instrumental deliveries and fetal outcome. The maternal mortality ratio for
      teenagers was 1835 per 100,000 live births. There were no deaths among the older
      nullipara. It is concluded that the differences in obstetric intervention rates
      and maternal outcome are due to poor utilization of antenatal care and other
      social disparity.

PMID- 17540085
TI  - Maternal mortality in a Nigerian teaching hospital - a continuing tragedy.
AB  - The aim of this review is to determine the maternal mortality ratio (MMR) in a
      Nigerian tertiary health institution (University of Ilorin Teaching Hospital,
      Ilorin, Nigeria). The review was done through a retrospective analysis of
      maternal mortality records. The MMR for the 6-year period (1997-2002) was 825 per
      100,000 live births. The common causes of maternal mortality included severe pre
      eclampsia/eclampsia, 30 (27.8%); haemorrhage, 22 (20.4%) and complications of
      unsafe abortion 16 (14.8%). Grandmultiparous and patients aged 40 years and above
      were at the highest risk. This hospital-based MMR is very high and when compared
      with previous reports showed a 150% increase. Most of the maternal deaths are,
      however, preventable. Increased efforts at educating women, improvement of the
      socioeconomic conditions of the populace and strong political commitment in
      making emergency obstetric care available in rural and district hospitals are
      some of the measures that need to be adopted to reduce this avoidable tragedy.

PMID- 17540086
TI  - Teenage pregnancies and their obstetric outcomes.
AB  - This study was conducted to evaluate the obstetric performance of teenage women
      in India. In total, 13,210 women were included in the study, of whom 840 were
      teenagers (<19 years) and 12,370 were > or =20 years. Antepartum, intrapartum and
      postpartum events were recorded and comparative analysis was done. We found that
      teenage women were at a significantly higher risk for development of severe
      anaemia (relative risk [RR] 1.61, P value <0.02), eclampsia (RR 1.95, P value
      <0.05), preterm labour (RR 1.25, P value <0.001), intrauterine growth retardation
      (RR 2.29, P value <0.001) and low birth weight (RR 1.24, P value <0.001).
      Assisted delivery (11.78% versus 2.23%, P value <0.001) was significantly more
      common and caesarean delivery (9.64% versus 17.18%, P value <0.001) was
      significantly less common in teenagers. Moderate anaemia, mild pregnancy-induced
      hypertension, preeclampsia, premature rupture of membranes, antepartum
      haemorrhage and post dates were all significantly higher in > or =20 years group.
      To conclude, we found that teenage women are a high-risk group, which is
      aggravated by social and cultural factors. Special attention is required to
      educate these women for more positive outcomes.

PMID- 17540087
TI  - A simple method of assessing toilet construction and hygiene behaviour.

PMID- 17540088
TI  - Reasons for gynaecological consultations in children in Calabar, South Eastern
      Nigeria.
AB  - Childhood gynaecological disorders as seen in the University of Calabar Teaching
      hospital (UCTH), Calabar, Nigeria, over a 10-year period were studied. The aim
      was to establish the incidence and pattern of presentation of these disorders.
      Childhood gynaecological disorders constituted 3.1% of gynaecological admissions
      in UCTH. Vaginal laceration following rape was the most common disorder
      accounting for 54.8% of the cases. This was most common in the 8 to 11-year age
      group (52.2%). Vaginal bleeding was the most common presenting symptom (63.1%)
      and repair of vaginal laceration the most common procedure performed (54.8%).

PMID- 17540089
TI  - Tubal factor infertility in Benin City, Nigeria - sociodemographics of patients
      and aetiopathogenic factors.
AB  - In Africa, infertility constitutes a major gynaecological complaint and causes
      enormous socio-psychological stress to the patients. This study examined
      retrospective data at the University of Benin Teaching Hospital, Benin City,
      Nigeria, over a 5-year period to determine the factors associated with tubal
      infertility. Tubal infertility was confirmed in 13.5% of the 1181 new cases of
      infertility over the study period. The mean age of the patients was 33.2+/-9.5
      years. Over 65% were nulliparous and all socioeconomic classes were affected.
      Major associated factors included infections such as post-abortal sepsis,
      puerperal sepsis and pelvic inflammatory disease (PID). Infertility is largely
      preventable. Attention should be focused on reducing the incidence of unsafe
      abortion and its consequences, providing clean and safe delivery as well as
      reducing the incidence of and ensuring proper treatment of any cases of PID.
      Infertility is largely preventable. Attention should be focused on reducing the
      incidence of unsafe abortion and its consequences, providing clean and safe
      delivery as well as reducing the incidence of and ensuring proper treatment of
      any cases of PID.

PMID- 17540090
TI  - Perceived determinants of the utilization of maternal health-care services by
      rural women in Kogi State, Nigeria.

PMID- 17540091
TI  - Missing maternal deaths: lessons from Souro Sanou University Hospital in Bobo
      Dioulasso, Burkina Faso.
AB  - We investigated the location of maternal deaths in the Souro Sanou University
      Hospital of Bobo-Dioulasso, Burkina Faso. In all, the deaths of 585 women of
      reproductive age (12-49 years) were reviewed, and 132 (22.6%) were found to be
      maternal. Of these132, 43 (33.6%) occurred outside of the maternity unit. Some
      direct causes of death (eclampsia and sepsis) and indirect causes of death
      (cardiac illness and HIV/AIDS) would be omitted if only cases occurring on the
      maternity ward are investigated. Alarmingly, 93 (70%) of the 132 maternal deaths
      would have been missed in this hospital if we had used a narrow search process
      (excluding non-maternity wards) and narrow definition (excluding indirect
      causes). In conclusion, the results of this study demonstrate the potential for
      seriously underestimating the magnitude of maternal mortality within facilities
      and for neglecting pregnant or recently pregnant women dying in non-maternity
      wards and from indirect complications.

PMID- 17540092
TI  - Fetal sex-determination in Delhi: a population-based investigation.
AB  - A population-based cross-sectional inquiry was carried out in Delhi to assess the
      practice of fetal sex determination, sex-selective abortions and awareness about
      the related law. A total of 1514 respondents, selected through multistage cluster
      sampling from all across Delhi, were interviewed using a pretested,
      semistructured questionnaire. Legal awareness (73.6%) was significantly better
      among the male and urban respondents. Only 39 (2.6%) of the respondents had ever
      gone for fetal sex determination. In 17 (43.6%) of them, it was done in spite of
      being aware of its unlawfulness, and in 33 (84.6%), the couple had one or more
      living male children. Frequency of fetal sex determination was comparable for
      slum and urban areas. Fifty-six additional cases of fetal sex determination,
      occurring in the neighbourhood of the respondents, were also reported. A total of
      28 cases of female feticide were reported. Awareness about the illegality of
      fetal sex determination has improved, compared with the 1997-1998 data collected
      from East Delhi (55.3-73.6%). However, this comparison also shows a marginal
      increase in the practice of fetal sex determination (2.1-2.6%). In all cases of
      feticide, a qualified doctor was involved. A number of couples abandoned the
      abortion plan midway, even after detecting that the fetus was female, and there
      were occasional cases where the doctor refused to abort the female fetus.

PMID- 17540093
TI  - Increasing trends in seroprevalence of human hydatidosis in North India: a
      hospital-based study.
AB  - A retrospective analysis of laboratory data of 3290 clinically suspected and/or
      radiologically confirmed cases of hydatidosis revealed that 495 (15%) were
      positive for specific antibody response. Casoni's test was positive in 481/1938
      (24.82%) patients. A significant increase (P<0.001) in seropositivity was
      observed during the last 5 years (23.12%, 1999-2003) as compared with previous
      years (10.97%, 1984-1998), and a similar increase (P<0.001) in positive Casoni's
      test was also observed (33.83%, 1999-2003 versus 21.38%, 1984-1998) during the
      same time period.

PMID- 17540094
TI  - Influence of acute renal failure in patients with cerebral malaria - a hospital
      based study from India.
AB  - We analysed 110 adult patients with cerebral malaria, 38 of whom had serum
      creatinine above 3 mg%, to study the effect of acute renal failure (ARF) on
      survival. Patients with cerebral malaria had an increased risk of death (39.5%
      versus 13.9%) when also suffering from ARF. For each one log unit increase of
      creatinine at admission, odds of death increased by a factor of 10.8 (95%
      confidence interval 3.0-39.4).

PMID- 17540095
TI  - Conceptual model for the prevention of maternal mortality in Nigeria.
AB  - Maternal mortality rates are much higher in developing countries than in the
      developed countries. In Nigeria, rates between 500 and 1500 per 100,000 are
      common. Questionnaires were administered to 30 primary health centres in Edo
      central senatorial district of Nigeria in order to find out the staffing, 24 h
      staff coverage of the primary health centre and difficulties encountered in
      referring patients. It was found that most of the primary health centres had no
      doctor coverage. The average number of midwives per centre was two, and transport
      was not usually available for transfers especially at night. It was concluded
      that lack of commitment on the part of all tiers of government was the reason
      behind the high mortality rates, and a conceptual model of one resident doctor
      per centre, with a 24 h coverage by midwives and a central ambulance centre for
      each local government area, was proposed for the reduction of maternal mortality,
      using the available resources in Nigeria.

PMID- 17540096
TI  - A challenge for monitoring iodine deficiency disorders in rural Nepal.
AB  - Developing a strategy for monitoring iodine deficiency disorders (IDD) remains a
      big challenge in rural Nepal where great variations could exist in IDD status. To
      explore the possibility of variation in urinary iodine excretion (UIE) level in
      rural settings, we carried out a detailed study of UIE among 586 school children
      of 20 schools in five villages. Our data revealed statisitically significant
      differences in UIE values among rural villages and schools in the same villages.
      The policy-makers should keep such variations in mind for a successful monitoring
      of IDD in Nepal and other countries where such variations may exist.

PMID- 17540097
TI  - Critical care management of gynaecological patients in Enugu, Nigeria.
AB  - A retrospective study of the management of gynaecological patients admitted to
      the general intensive care unit (ICU) of the University of Nigeria Teaching
      Hospital (UNTH), Enugu, Nigeria, over a 6-year span was carried out. Out of a
      total of 816 patients admitted to the ICU during the study period, 21 (2.6%) were
      gynaecological patients with the following diagnoses: generalized sepsis,
      postoperative respiratory distress, hypovolaemic shock, preoperative anaemia and
      mennorhagia, and major surgery with potential for major complications. The
      mortality rate was 28.6% with six deaths, sepsis being the major cause of death
      (four fatalities).

PMID- 17540098
TI  - Caesarean myomectomy in Aba, south-eastern Nigeria.

PMID- 17540099
TI  - Injuries from cow gore in adults among Fulani.
AB  - A retrospective study of 32 patients managed for cow gore injuries. The abdomen
      was involved in 16 (50%) patients, scrotum in six (18.9%), neck in three (9.3%)
      and other sites in seven (22.8%). All injuries were penetrating in nature and
      laparotomy was done on 17 (53%) patients.

PMID- 17540100
TI  - Aspergilloma in a hydatid cavity.

PMID- 17540101
TI  - Paediatric burns: management problems in a teaching hospital in north western
      Nigeria.
AB  - The records of 168 children managed for burns in a teaching hospital in
      northwestern Nigeria, between April 1998 and March 2003, were assessed to
      determine the factors that are responsible for high rates of morbidity and
      mortality in paediatric burns. The causes of burns were hot water in 86 cases
      (51.2%), flame in 45 (26.8%), hot soup in 32 (19%) and electricity in five (3%).
      The main complications were wound infections in 109 (64.9%) patients, anaemia in
      68 (40.5%), malnutrition in 54 (32.1%), contracture in 50 (29.8%), persistent
      hypothermia in 27 (16.1%), tetanus in 14 (8.3%) and one case (0.6%) of massive
      upper gastrointestinal bleeding, possibly as a result of Curling's ulcer.

PMID- 17540102
TI  - Genital TB: an unusual threat to reproductive health in the tropics.

PMID- 17540103
TI  - Features of childhood leukaemia in Tanzania.

PMID- 17540104
TI  - Mothers' perception of the use of nasogastric feeding tubes on their children.

PMID- 17540105
TI  - Prevalence of HIV infection among patients undergoing surgery in a mission
      hospital in a semi-urban community in Nigeria.

PMID- 17540106
TI  - Prevalence of hyperlipidaemia among insulin-dependent and non-insulin-dependent
      diabetes mellitus patients in Delta State, Nigeria.

PMID- 17540107
TI  - Louse-borne relapsing fever and malaria co-infection in Ethiopia.

PMID- 17540108
TI  - Why people think they should care for the elderly in Nigeria.

PMID- 17540109
TI  - The prevalence of intestinal parasite infections among schoolchildren of Van
      province, Turkey.

PMID- 17540110
TI  - Effectiveness of the oral polio vaccine and prospects for global eradication of
      polio.

PMID- 17540111
TI  - The clean catch technique for urine collection in infants and young children.

PMID- 17540112
TI  - Malaria awareness of village health workers from Sundargarh in Orissa - the state
      contributing half of the malaria-related deaths in India.

PMID- 17540113
TI  - Characterization of surface microphase structures of poly(urethane urea)
      biomaterials by nanoscale indentation with AFM.
AB  - Atomic force microscopy utilizing both tapping mode and force mode imaging is
      used to visualize the separated microphases in poly(urethane urea) films under
      ambient and aqueous conditions. The topography of the PUU surface changed upon
      hydration with the formation of nanometer-sized features on the surface. The
      surface becomes enriched in hard domains with hydration time and this enrichment
      is irreversible after dehydration. Force mode measurements were used to quantify
      mechanical properties as both indentation and modulus measurements. Analysis of
      the modulus during indentation reveals the three-dimensional nature of the
      structures, with the surface being covered by a 2-20-nm-thick soft segment
      overlayer under ambient conditions, while hydration leads to the loss of this
      overlayer. The force measurements also reveal the presence of regions having
      modulus values between those of the hard and soft phases and located spatially
      near the interface between the hard and soft domains. However, such regions with
      intermediate modulus were only rarely seen following hydration. Calculation of
      the Young's modulus from the compression data shows that hydration increases the
      modulus of the PUU surface by both enrichment of the amount of hard domain
      present and increasing the modulus of the individual hard and soft phases
      themselves. Direct visualization of the distribution of these different domains
      on the surface by nanoscale measurements provides an important path to
      characterizing the relationships between the surface properties of these
      materials and subsequent performance in biomedical applications.

PMID- 17540114
TI  - Surface modification of biodegradable electrospun nanofiber scaffolds and their
      interaction with fibroblasts.
AB  - Biodegradable polymers, such as poly(glycolic acid) (PGA), poly(L-lactic acid)
      (PLLA) and poly(lactic-co-glycolic acid) (PLGA), were dissolved individually in
      the proper solvents and then subjected to electrospinning process to make
      nanofibrous scaffolds. Their surfaces were then chemically modified using oxygen
      plasma treatment and in situ grafting of hydrophilic acrylic acid (AA). The fiber
      thickness, pore size and porosity were estimated to 200-800 nm, 2-30 microm and
      94-96%, respectively, and these properties were insignificant in the PGA, PLLA
      and PLGA nanofibrous scaffolds. The ultimate tensile strength of PGA was about
      2.5 MPa on average and that of PLGA and PLLA was less than 2 MPa. The elongation
      at-break was 100-130% for the three nanofibrous scaffolds. When the surface
      properties of AA-grafted scaffolds were examined, higher ratios of oxygen to
      carbon, lower contact angles and the presence of carboxylic (-COOH) groups were
      identified. The properties were significantly different from those of the
      unmodified nanofibrous scaffolds. Fibroblasts once seeded on the scaffolds were
      spreading over large surface area on the AA-grafted surface as compared to the
      unmodified PGA, PLLA and PLGA nanofibrous scaffolds. Cultured for up to 6 days,
      the fibroblast proliferation was found to be much better on the surface-modified
      nanofibrous scaffolds. The present study showed that, with the use of plasma
      treatment and AA grafting, the hydrophilic functional groups could be
      successfully adapted on the surface of electrospun nanofibrous scaffolds. Those
      surface-modified scaffolds made significant improvement on cell attachment and
      proliferation in vitro.

PMID- 17540115
TI  - Measurement of composite shrinkage using a fibre optic Bragg grating sensor.
AB  - Fibre Bragg grating is used to determine resin-based composite shrinkage. Two
      composite resins (Freedom from SDI and Z100 from 3M) were tested to determine the
      polymerization contraction behaviour. Each sample of resin was prepared with an
      embedded fibre Bragg grating. A LED activation unit with wavelength from 430 nm
      to 470 nm (Dabi Atlante) was used for resin polymerization. The wavelength
      position of the peak in the optical reflection spectra of the sensor was
      measured. The wavelength shift was related to the shrinkage deformation of the
      samples. Temperature and strain evolution during the curing phase of the material
      was monitored. The shrinkage in the longitudinal direction was 0.15 +/- 0.02% for
      resin Z100 (3M) and 0.06+/-0.01% for Freedom (SDI); two-thirds of shrinkage
      occurred after the first 50 s of illumination.

PMID- 17540116
TI  - Three-dimensional porous hydroxyapatite/collagen composite with rubber-like
      elasticity.
AB  - A three-dimensional porous hydroxyapatite/collagen (HAp/Col) composite with a
      random pore structure was fabricated using freeze-drying processes; the self
      organized HAp/Col nanocomposite with a weight ratio of 80.5:19.5, freeze-dried,
      was kneaded in 100 mM sodium phosphate buffer, frozen at -20 degrees C and freeze
      dried. The cross-linkage of Col molecules was introduced dehydrothermally at 140
      degrees C in vacuo. The porous composite had a porosity of 94.7% with pore sizes
      between 200 and 500 microm. The compressive stress for the wet porous composite
      in phosphate buffer saline (PBS) was gradually decreased during 20 days
      incubation with a small amount of weight loss. The cyclic and time-course
      compression tests showed good repeatability of stress and well-recovery of its
      height, and caused no collapse of the porous composite. The implantation of the
      porous composite in rat bone holes showed the biodegradable property and new bone
      formation occurred in the pores without inflammatory response. The porous
      composite fabricated has good flexibility and rubber-like elasticity, and is a
      promising bone regenerative material.

PMID- 17540117
TI  - Synthesis and characterization of functional elastomeric poly(ester amide) co
      polymers.
AB  - A new family of random co-poly(ester amides)s (co-PEAs) having reactive pendant
      functional carboxylic acid groups were synthesized by co-polycondensation of di-p
      toluenesulfonic acid salts of bis-(L-alpha-amino acid (L-leucine and/or L
      phenylalanine)) alpha,omega-alkylene diesters with active diesters of
      dicarboxylic acids using di-p-toluenesulfonic acid salt of L-lysine benzyl ester
      as a co-monomer. The lateral benzyl ester groups in the L-lysine segment of co
      PEAs were subsequently transformed into free COOH groups by catalytic
      hydrogenolysis using Pd black as a catalyst. The co-PEA-based polyacids obtained,
      as well as the original co-PEA having lateral benzyl ester groups were
      characterized by standard methods. In vitro biodegradation studies in the
      presence of hydrolases like alpha-chymotrypsin and lipase showed significant
      enzymatic-catalyzed biodegradation of these co-PEAs. These co-PEA-based polyacids
      were used for covalent attachment of iminoxyl radicals (4-amino-TEMPO) and in
      vitro biodegradation of 4-aminoTEMPO attached polymer was studied along with
      releasing kinetic of iminoxyl radical.

PMID- 17540118
TI  - Effect of surface modification of polymer beads on the mechanical properties of
      acrylic bone cement.
AB  - The effect of surface modification of polymer filler on the static mechanical
      properties of acrylic bone cement was studied. The surface of polymer beads was
      modified with carboxylic and amino groups by photochemical reaction with azide
      compounds. Monomer modifiers (maleic anhydride, methacrylic acid and p
      aminostyrene) are attached to the functionalized surface of polymer beads.
      Functional allyl groups, which are capable of the graft polymerisation reaction,
      are attached to the surface via photochemical reaction with N-(2-nitro-4
      azidophenyl)-N-(-propen) amine. This approach to bone cement provides the
      additional covalent bonds between the polymer beads and the inter-bead matrix.
      The static mechanical properties of bone cements containing modified polymer
      beads were investigated and compared with the static mechanical properties of
      unmodified cements. The absolute values of compressive strength for the modified
      and unmodified cements were found to be similar. An increase in flexural strength
      for the modified cements (dry and after water storage) was observed. The
      structure of the surface functional groups affects the methyl methacrylate
      grafting resulting in a higher value of flexural strength for the maleic
      anhydride- and p-aminostyrene-modified cements. The scanning electron microscopy
      examination of the fracture surface of the cement samples showed an improvement
      of the adhesion between the beads and the matrix after modification.

PMID- 17540119
TI  - UV surface modification of a new nanocomposite polymer to improve
      cytocompatibility.
AB  - A novel modified nanocomposite was studied for the adhesion and proliferation of
      the human umbilical vein endothelial cell (HUVEC) line EA.hy926. The
      nanocomposite under investigation was poly(carbonate-urea)urethane with
      silsesquioxane nano-cages, here in the form of a mixture of two polyhedral
      oligomeric silsesquioxanes. The nanocomposite surfaces were exposed to
      ultraviolet (UV) light of a Xe(*)(2)-excimer lamp at a wavelength of 172 nm in an
      ammonia atmosphere. The effects of the irradiation were characterized by atomic
      force and scanning electron microscopy (AFM, SEM), X-ray photo-electron
      spectroscopy (XPS), Fourier-transform infrared spectroscopy (FT-IR) using an
      attenuated total reflection (ATR) device and measurements of advancing water
      contact angle (CA). The irradiation resulted in the introduction of new
      hydrophilic N- and O-containing groups into the surface, which was initially
      amphiphilic, while surface morphology remained mainly unchanged. Slight chemical
      changes were also observed for the silsesquioxane nano-cages at the surface. Onto
      the untreated and irradiated samples HUVECs were seeded and grown for various
      durations in culture. Standard tissue-culture polystyrene (PS) was employed as a
      positive control to check the efficiency of the cell-culture methods. Viability
      and proliferation of the cells were then assessed using a non-radioactive assay.
      Compared to the untreated nanocomposite polymer, irradiation times of at least 5
      min resulted in a significantly increased cell proliferation between 3 and 8 days
      after seeding with the HUVEC line EA.hy926.

PMID- 17540120
TI  - Attachment, spreading and short-term proliferation of human osteoblastic cells
      cultured on chitosan films with different degrees of acetylation.
AB  - Chitosan (Ch) is being actively investigated as a non-protein template for the
      growth of an increasing number of anchorage-dependent cells, including
      chondrocytes and bone cells. In the present work, Ch films with degrees of N
      acetylation (DAs) in the range of 4 to 49% were evaluated with respect to the
      attachment, spreading and short-term proliferation of osteoblasts, using human
      osteoblastic MG-63 cells. The films were characterized in terms of surface
      morphology and surface charge by atomic force microscopy and streaming potential
      measurements, respectively. Cell attachment was assessed after 3 and 24 h of cell
      culture. After 24 h of incubation, cell attachment was found to be dependent on
      the DA, lower DAs favouring cell adhesion. With time, cell spreading and
      cytoskeleton organization were only attained for DAs <or= 13%. Regarding cell
      proliferation, cells grown on films with the lowest DA (4%) revealed a higher
      specific growth rate as compared to those grown on films with higher DAs. Films
      with a DA of 49% failed to sustain cell proliferation. In addition, a longer lag
      phase was observed on Ch, as compared to TCPS, in accordance to an observed delay
      of cell spreading. The present findings revealed that differences in the DA as
      small as 9% may be critical in terms of the osteoblast response to two
      dimensional Ch-based matrices.

PMID- 17540122
TI  - Floppy eyelid syndrome.
AB  - In this review, we define characteristics of floppy eyelid syndrome, as well as
      related syndromes, such as lax eyelid syndrome. Presenting symptoms, ocular
      signs, and important clinical examination techniques are described, and
      associated ocular and systemic conditions, as well as corresponding
      pathophysiology are discussed. Significant new histopathologic findings in floppy
      eyelid syndrome and recent surgical developments are summarized. This review
      provides a critical update of floppy eyelid syndrome and aids the ophthalmologist
      in new methods of assessment and management.

PMID- 17540123
TI  - Optic neuritis.
AB  - The term optic neuritis denotes primary inflammation of the optic nerve. When the
      clinical history and examination suggest optic neuritis and the optic disk
      appears normal, the term retrobulbar optic neuritis is used. Critical elements in
      establishing the diagnosis are a detailed history and an accurate examination.
      For this reason, the ophthalmologist must be familiar with the clinical profile
      of optic neuritis.

PMID- 17540125
TI  - LASIK and dry eye.
AB  - Dry eye is one of the most common complications after laser-assisted in situ
      keratomileusis (LASIK). The clinical signs of post-LASIK dry eye include positive
      vital staining of ocular surface, decreased tear film breakup time and Schirmer
      test, reduced corneal sensitivity, and decreased functional visual acuity. The
      symptoms and signs last at least 1 month after LASIK. Although the mechanisms for
      developing post-LASIK dry eye are not completely understood, loss of corneal
      innervation by flap-making may affect the reflex loops of the corneal-lacrimal
      gland, corneal-blinking, and blinking-meibomian gland, and blinking-meibomian
      gland, resulting in decreased aqueous and lipid tear secretion and mucin
      expression. As LASIK enhancement by flap-lifting induces less dry eye symptoms
      and signs than first surgery, it is suggested that other factors rather than loss
      of neurotrophic effect may be involved in the mechanisms of post-LASIK dry eye.
      The treatments of dry eye include artificial tears, topical cyclosporine, hot
      compress, punctal plugs, and autologous serum eye drops. For patients with severe
      preoperative dry eye, a combination of punctal plugs and serum eye drops is
      required to be used before surgery.

PMID- 17540127
TI  - Transient monocular visual loss.
AB  - Transient monocular visual loss may be caused by a variety of ophthalmic and
      systemic conditions. Management depends on identifying the cause. Embolic
      occlusions of arteries supplying the eye are a most important cause. Such emboli
      often arise from the heart, aorta, and internal carotid arteries. The most common
      embolic substances are white platelet-fibrin and red erythrocyte-fibrin thrombi,
      cholesterol crystals, and calcific particles. Retinal vasoconstriction is another
      important cause of transient monocular visual loss. The conditions that cause
      anterior ischemic optic neuropathy may occasionally cause transient visual loss.
      Transient monocular visual loss may also be related to conditions that cause
      papilledema and some conditions intrinsic to the eye, such as optic disk drusen
      and colobomas.

PMID- 17540132
TI  - Million women study report on ovarian cancer meets more criticism.

PMID- 17540133
TI  - Oral bisphosphonates and osteonecrosis of the jaw: are the MHRA recommendations
      appropriate?

PMID- 17540134
TI  - Bisphosphonate-associated osteonecrosis of the jaw.
AB  - The term 'osteonecrosis of the jaw' is typically used to describe the exposure of
      bone within the oral cavity. These lesions are often painful and can result in
      pathological fracture and disfigurement in severe cases. Infection and dental
      extractions commonly precede presentation, although lesions can occur
      spontaneously. There are no clear effective management strategies; surgery often
      makes the situation worse. The aetiology is far from clear. Historically, it was
      mainly associated with exposure to 'white phosphorus' contained in safety
      matches. More recently, it has presented as a complication of head and neck radio
      therapy. The vast majority of contemporary reports refer to high-dose intravenous
      bisphosphonates used in the oncological setting. However, oral bisphosphonates,
      for the common indication of postmenopausal osteoporosis, have also been
      implicated, although the number of cases is minuscule considering the number of
      worldwide prescriptions. Osteonecrosis of the jaw poses a significant problem in
      oncology, but whether this worry is transferable to metabolic bone disease only
      time will tell. Certainly, further research into its pathophysiology and
      management is merited. With regard to management of postmenopausal osteoporosis,
      practice should not necessarily be altered at this early stage; however, pre
      treatment worries regarding dental health should perhaps instigate a
      precautionary dental review.

PMID- 17540135
TI  - Skin ageing.
AB  - Cutaneous ageing manifests itself as a progressive reduction in maximum function
      and reserve capacity of skin tissue. It is not a unique and uniform biological
      event. Skin comprises three layers: epidermis, dermis and subcutaneous tissue.
      Collagen atrophy is a major factor in skin ageing. There is a strong correlation
      between skin collagen loss and estrogen deficiency due to the menopause. Skin
      ageing, especially in the face, is associated with a progressive increase in
      extensibility and a reduction in elasticity. With increasing age, the skin also
      becomes more fragile and susceptible to trauma, leading to more lacerations and
      bruising. Furthermore, wound healing is impaired in older women. Estrogen use
      after the menopause increases collagen content, dermal thickness and elasticity,
      and it decreases the likelihood of senile dry skin. Large-scale clinical trials
      are necessary to help make informed recommendations regarding postmenopausal
      estrogen use and its role in the prevention of skin ageing.

PMID- 17540136
TI  - Systemic lupus erythematosus and hormone replacement therapy.
AB  - The indications for hormone replacement therapy (HRT) in postmenopausal women is
      the treatment of climacteric symptoms and the prevention of osteoporosis. Women
      with systemic lupus erythematosus (SLE) are more likely to have a premature
      menopause, osteoporosis and cardiovascular disease. HRT can induce SLE flares and
      cardiovascular or venous thromboembolic events. Therefore it should not be used
      in women with active disease or those with antiphospholipid (aPL) antibodies. In
      general, it should be used only for patients without active disease, a history of
      thrombosis or aPL antibodies. Non-oral administration of estrogen is recommended
      because of its lesser effect on coagulation. With regard to the progestogen,
      progesterone or pregnane derivatives are preferred. Otherwise, non-estrogen-based
      strategies should be used.

PMID- 17540137
TI  - Improving quality of life after breast cancer: prevention of other diseases.
AB  - Many women with breast cancer will be diagnosed at an early stage through
      screening programmes. Furthermore, most women affected by breast cancer will not
      die from it but from other diseases, owing to recent improvements in treatment.
      This article assesses whether breast cancer survivors suffer more frequently from
      other diseases. Specifically, it examines whether they have a higher incidence of
      other cancers, cardiovascular events and osteoporotic fractures. Women with
      breast cancer and three or more co-morbid conditions have a 20-fold higher rate
      of mortality from causes other than breast cancer and a 4-fold higher rate of all
      cause mortality when compared with patients who have none. Breast cancer
      survivors are at increased risk of other cancers, such as stomach, colorectal and
      lung. Radiotherapy, trastuzumab and aromatase inhibitors increase the risk of
      cardiovascular disease. However, tamoxifen does not, although it is associated
      with an increased risk of venous thromboembolism. Aromatase inhibitors, but not
      tamoxifen, increase the risk of osteoporotoic fracture and bisphosphonate therapy
      should be considered.

PMID- 17540138
TI  - Dehydroepiandrosterone (DHEA) and the menopause: an update.
AB  - Since we last reviewed this topic in 2001, considerably more information about
      dehydroepiandrosterone (DHEA) has accrued, but this has not necessarily left us
      any wiser about the use of this steroid in postmenopausal women. There is no
      further evidence that DHEA supplementation is likely to be useful in the
      prevention of cardiovascular disease or cognitive impairment, or in the promotion
      of wellbeing. Evidence has, however, accumulated for beneficial effects of DHEA
      on osteoporosis, both in postmenopausal women and in patients receiving long-term
      glucocorticoid therapy. What is also emerging is a link between low DHEA levels
      and cardiovascular risk, and between high DHEA levels and breast cancer risk. In
      fact, the benefits and adverse effects of DHEA administration in postmenopausal
      women increasingly resemble those of conventional hormone replacement therapy.
      Overall, we conclude that DHEA is not currently to be recommended for therapeutic
      use in the majority of postmenopausal women. However, DHEA supplementation may be
      of benefit in two specific groups of women: those with the lowest circulating
      levels of DHEA; and those for whom osteoporosis is a particular problem.

PMID- 17540139
TI  - Women's attitudes to hormone replacement therapy, alternative therapy and sexual
      health: a web-based survey.
AB  - OBJECTIVE: To survey women's views on hormone replacement therapy (HRT),
      alternative therapies and sexual health using the Internet. Study design and main
      outcome measures. Three questionnaires were offered on a UK, patient-tailored,
      independent, clinician-led dedicated menopause website. They covered HRT,
      alternative therapies and sexual health. The anonymous responses of the users of
      the website were analysed. RESULTS: There were 1026, 1072 and 1002 responses for
      the HRT, alternative therapies and sexual health questionnaires, respectively. On
      the first, 75% of respondents were in favour of HRT; 36% felt media reports of
      the risks of HRT had been exaggerated and 73% of women did not know enough about
      HRT to make informed choices. In relation to alternative therapies, 85% of
      respondents felt they did not know enough to make informed choices, 71% received
      no advice before starting an alternative therapy and 69% were unaware of possible
      interactions. Ninety-five per cent would try alternative therapies before HRT in
      the belief that they were more natural and 68% were prepared to pay more than
      pound10 a month for such therapies. On the questionnaire on sexual health, 88% of
      respondents indicated that they believed an active sex life was important. Fifty
      three per cent recorded that they experienced dyspareunia, but 51% of women hid
      their symptoms and 31% made excuses to avoid intercourse; 54% felt their
      confidence had been adversely affected. Only 20% had discussed their symptoms
      with health professionals and only 12% were using prescribed treatment.
      CONCLUSIONS: Online questionnaires are a useful means to obtain data. Our surveys
      raised several issues, including the observations that the majority of women said
      they did not know enough about HRT and alternative therapies to make informed
      choices. There appeared to be many women with vaginal symptoms who had not spoken
      with a health professional and therefore were untreated.

PMID- 17540140
TI  - Home care needs of extremely obese elderly European women.
AB  - OBJECTIVE: To examine the health and needs of extremely obese women aged over 65
      years receiving home care in Europe. STUDY DESIGN: A cross-sectional assessment
      study based on the Aged in Home Care (AdHOC) project recruited 2974 women aged 65
      or over who were receiving home care at 11 sites in European countries. Extreme
      obesity was defined as 'Obesity of such a degree as to interfere with normal
      activities, including respiration'. MAIN OUTCOME MEASURES: Resident Assessment
      Instrument for Home Care (RAI-HC version 2.0); Activity of Daily Living Scale;
      Instrumental Activity of Daily Living Scale; the Minimum Data Set Cognitive
      Performance Scale; and a health profile. RESULTS: One hundred and twenty women
      (4.0%) were extremely obese. They were younger than their thinner counterparts,
      with a median age of 78.3 versus 83.3 years, and they more often had multiple
      health complaints and needed more help with mobility outside the home. The
      extremely obese had received home care longer than the non-extremely obese
      (median 28.7 versus 36.6 months). Extremely obese women also needed more help
      with personal care than the other group and, due to lower age, they were less
      cognitively impaired. CONCLUSIONS: Extreme obesity is a problem that increasingly
      affects home care of elderly women.

PMID- 17540141
TI  - Exercise-related menstrual dysfunction: implications for menopausal health.
AB  - Physical activity is a well recognized approach to the enhancement of general
      health and wellbeing in both healthy and diseased populations. However, excessive
      activity can result in exercise-related menstrual dysfunction (ERMD), which can
      adversely affect bone health and increase the risk of infertility and
      cardiovascular events in later life. Physicians should maintain a high awareness
      of EMRD in assessing health risks in the menopausal woman.

PMID- 17540142
TI  - [A comparative study of patients with methicillin susceptible versus methicillin
      resistant Staphylococcus aureus bacteremia: epidemiology and prognostic factors].
AB  - BACKGROUND AND OBJECTIVE: The influence of methicillin resistance in
      Staphylococcus aureus bacteremia (SAB) continues to be controversial. The aim of
      this study was to evaluate risk factors and mortality predictors in patients with
      SAB and the influence of methicillin resistance in mortality (SAMSB vs SAMRB).
      PATIENTS AND METHOD: Prospective study including 213 in-patients with SAB.
      RESULTS: Of 213 episodes of SAB, 131 (61.5%) were due to SAMS and 82 (38.5%) to
      SAMR. Risk factors associated with SAMRB were: nosocomial infection, presence of
      an ultimately or rapidly fatal underlying disease, diabetes mellitus, intravenous
      catheters, previous ICU hospitalization and therapy with broad-spectrum
      antibiotics. Severity and complications were more frequent in patients with
      SAMRB. Mortality was 42.6% in SAMRB cases vs 16% in SAMSB cases (p < 0.05).
      Multivariate analysis showed as independent predictors of mortality in patients
      with SAB: presence of an ultimately or rapidly fatal underlying disease, acute
      severity of illness at onset and inappropriate empirical therapy; methicillin
      resistance was not an independent predictor of mortality. CONCLUSIONS:
      Methicillin resistance was not an independent predictor of mortality in patients
      with SAB. Presence of a fatal underlying disease, acute severity of illness at
      onset and inappropriate therapy were the main prognosis factors in patients with
      SAB.

PMID- 17540143
TI  - [Validity of the questionnaire MOS-SSS of social support in neoplastic patients].
AB  - BACKGROUND AND OBJECTIVE: Previous studies have pointed out how the perception of
      social support benefits the wellbeing of patients. The main objective in this
      study is to adapt and validate the MOS-SSS (Medical Outcomes Study-Social Support
      Survey) questionnaire to measure social support. PATIENTS AND METHOD: In a sample
      of 400 oncology out-patients, in order to validate the MOS-SSS questionnaire, we
      have applied a exploratory factorial analysis. The factors were extracted by
      principal components and varimax rotation. Then, we compared the dimensions of
      the questionnaire with other variables as size of social network, sex and age.
      RESULTS: We have observed a high reliability of the MOS-SSS questionnaire, with
      the alpha coefficient around 0.94 . By a factorial analysis, we have extracted 3
      factors: emotional/informational support, affective support and instrumental
      support. The fourth dimension included in the original questionnaire, positive
      social interaction, was included in the emotional/informational support
      dimension. Comparing the mean scores of the 3 dimensions with other variables
      (number of members in the family and friends, sex and age), we have observed that
      a high number of relatives and friends were related with a higher perception of
      social support. However, the men received more instrumental and
      emotional/informational support than women; and the age was not related with the
      perception of social support in patients with cancer. CONCLUSIONS: The MOS-SSS
      questionnaire is a valid instrument to assess the multidimensionality of the
      perception of social support in Spanish cancer patients.

PMID- 17540144
TI  - [Quality of life in long-term oral cancer survivors and comparison with reference
      values of Spanish people].
AB  - BACKGROUND AND OBJECTIVE: Health-related quality of life data are becoming an
      important supplement to information pertaining to treatment outcome for cancer
      patients. The purpose of this study was to evaluate the health-related quality of
      life of patients undergoing primary surgery for oral squamous cell carcinoma 5
      years or more after treatment compared with Spanish general populations norms.
      PATIENTS AND METHOD: Twenty-three oral cancer patients with cancer-free survival
      after surgery of > 5 years were enrolled. Health-related quality of life was
      assessed with one standardized questionnaire: the SF-36 Health Survey (Short Form
      36). Altogether 23 oral cancer patients (mean age: 55.3 years; 82% male) were
      included 5 years after surgery. RESULTS: The oral cancer patients' SF-36 scores
      did not differ significantly from those of an age- and sex-matched sample from
      the Spanish normative population, except role-mental and social functioning
      domains. The patients had better significant results than population norms
      (Wilcoxon test, p < 0.05) in vitality and health perceptions domains.
      CONCLUSIONS: These results provided patient-reported evidence that oral cancer
      survivors lived with a similar health-related quality of life compared with the
      general Spanish population. Recruitment is ongoing and a larger cohort in the
      future will allow further analysis of the trends demonstrated in this cohort.

PMID- 17540145
TI  - [Staphylococcus aureus bacteremia. Mortality and resistance to methicillin].

PMID- 17540146
TI  - [Primary prevention of type 2 diabetes using lifestyle intervention on high risk
      subjects in Catalonia, Spain].

PMID- 17540147
TI  - [Importance of the study of renal function in cardiology].
AB  - Main cardiopathies, heart failure and ischaemic heart disease, share common risk
      factors with renal insufficiency and these clinical entities are often present in
      the same patient. This association has important implications in primary
      prevention as well as in cardiological patients and this is why the prevention,
      diagnosis and treatment of renal insufficiency and common risk factors are a
      relevant strategy in current cardiologic practise.

PMID- 17540148
TI  - [Research opportunities and organizational aspects in Primary Health Care].

PMID- 17540149
TI  - [Radioiodine therapy in multinodular goiters].

PMID- 17540150
TI  - [Usefulness of prognostic scores of morbidity and mortality].

PMID- 17540151
TI  - [Evolution of causes of death in HIV patients: have they changed in the HAART
      era?].

PMID- 17540152
TI  - [Diagnosis, therapy and follow-up gastrointestinal stromal tumors].

PMID- 17540153
TI  - [Behcet's disease in Spain].

PMID- 17540154
TI  - [Primary liver lymphoma in a patient with hepatitis C].

PMID- 17540155
TI  - [Dermatitis due to zinc deficiency].

PMID- 17540156
TI  - The bacterial flora in the teat duct of ewes can protect against and can cause
      mastitis.
AB  - We studied the possible effects of bacterial populations within the teat duct, in
      the pathogenesis of ovine mastitis. In experiment I, 32 ewes were allocated into
      group A (ewes from which we isolated (+++ growth) coagulase-negative
      staphylococci), B (ewes from whose duct we isolated (+ growth) coagulase-negative
      staphylococci) or C (ewes from which we isolated Bacillus spp.) and subdivided
      into A1, B1, C1 (n=4; challenged by deposition of 1.250 cfu of Mannheimia
      haemolytica into the teat duct) or A2, B2, C2 (n=4; used as uninoculated
      controls); group D (n=8) contained ewes with no bacteria in their teat ducts and
      were challenged as above. There were less bacteriological isolations of flora (P
      = 0.018) and challenge (P<0.05) organisms from A1 than from A2 and D ewes; the
      severity of pathological findings in A1 (summed up score: 27) ewes was smaller
      than in D (summed up score: 36) ewes (P = 0.038). No such findings were evident
      with B1 or C1 ewes (P>0.4). In experiment II, ewes (groups E and F, n=6) from
      whose duct we isolated coagulase-negative staphylococci (+ growth) were used; in
      group G (n=6) ewes with no bacteria in their teat ducts were included. Teat
      chapping was applied in E and G ewes. All E ewes developed acute clinical
      mastitis within 24 h after teat chapping, although we had carried out no
      challenge; there were more bacteriological isolations of flora organisms from E
      than from F and G ewes (P < 0.001); the severity of pathological findings in E
      (score: 28) was greater than in F (score: 3) or G (score: 14) ewes. In experiment
      III, eight ewes with no bacteria in their teat ducts were allocated into group H
      or I (n=4) and challenged into the teat (group H) or into the gland (group I)
      with 10(6) cfu of a Staphylococcus simulans recovered from the teat duct of a
      group E ewe. Group H ewes developed transiently clinical followed by subclinical
      mastitis (based on bacteriological and cytological evidence), whilst group I ewes
      developed severe clinical disease. We conclude that staphylococcal flora present
      in high numbers within the teat duct of ewes can afford some protection against
      invading microorganisms. However with impeded defence mechanisms of the teat, the
      same flora may invade the mammary parenchyma and cause clinical mastitis.

PMID- 17540157
TI  - Splenic immune responses during canine visceral leishmaniasis.
AB  - Dogs are the main reservoir host for zoonotic visceral leishmaniasis caused by
      Leishmania infantum. In this study we investigated the immune response in spleens
      of L. infantum-infected dogs by measuring the mRNA expression levels for a wide
      panel of cytokines, transcription factors and chemokines. mRNA levels and
      parasite load were followed during 7 months of experimental infection and 14
      months post-treatment, and were compared to naturally-infected (NI) dogs.
      Similarly, serum anti-Leishmania IgG and IgG subclass levels were measured during
      experimental infection. An increase in IFN-gamma, T-bet, IP-10 and RANTES was
      found in the experimentally and NI dogs, implicating a substantial type-1 immune
      response during canine visceral leishmaniasis. IL-4, a type-2 associated
      cytokine, increased as early as one month after experimental infection, while IL
      5 was high at later stages. Interestingly, the expression levels of the Treg
      associated cytokines, IL-10 and TGF-beta, did not change during the infection.
      Total anti-Leishmania IgG and IgG subclasses increased during the experimental
      infection. However, no association with specific cytokine patterns was observed.
      Parasite load in the spleens increased as early as one month post-infection and
      remained high until treatment. The load was higher in the polysymptomatic NI dogs
      than in the experimentally-infected dogs. This study indicates that both type-1
      and type-2 immune responses occur in the spleen during canine L. infantum
      infection, and suggests that the early elevation of IL-4 might have a role in the
      persistence of parasites in the presence of high IFN-gamma expression.

PMID- 17540158
TI  - Identification of a novel foot-and-mouth disease virus specific T-cell epitope
      with immunodominant characteristics in cattle with MHC serotype A31.
AB  - To identify foot-and-mouth disease virus (FMDV) specific T-cell epitopes within
      the entire polyprotein sequence of the virus, 442 overlapping pentadecapeptides
      were tested in proliferation assays using lymphocytes from cattle experimentally
      infected with FMDV. Four months post-infection cells from all investigated
      animals (n = 4) responded by proliferation and interferon-gamma production to a
      peptide located on the structural protein 1D (VP1), amino acid residues 66-80.
      Major histocompatibility complex (MHC) serotyping of the investigated cattle
      indicated that all animals shared the MHC serotype A31 which comprises the class
      II allele DRB3 0701. This may explain the common recognition of this newly
      discovered epitope. Responses to other peptides could only be observed in one
      animal and rapidly declined during the time course of the study. These
      observations point to an immunodominant role of this epitope located on the
      protein 1D in cattle with MHC serotype A31.

PMID- 17540159
TI  - Avirulent viable but non culturable cells of Listeria monocytogenes need the
      presence of an embryo to be recovered in egg yolk and regain virulence after
      recovery.
AB  - The aim of this study was to assess the efficiency of the embryonated egg model
      to recover Viable But Non Culturable (VBNC) cells of Listeria monocytogenes. L.
      monocytogenes cells were incubated in filtered sterilised distilled water. The
      VBNC state was obtained after a 25 to 47 days incubation period (concentration of
      culturable cells less than 1 cfu/mL). Fifteen days after the VBNC state was
      reached, non culturability was checked in various media. One milliliter of each
      VBNC suspension that contained 10(4) metabolically active cells (i.e. Direct
      Viable Count + cells) was inoculated into the vitellus fluid of embryonated and
      non-embryonated eggs. Culturable cells were detected in a large proportion of the
      embryonated eggs (18/32), but not in the non-embryonated eggs (1/32). The
      recovery rate was higher after culture of the vitellus fluid plus embryo (18/32)
      than after culture of the vitellus fluid alone (6/32). The results indicate that
      the embryo likely plays a prominent part in the recovery process. The virulence
      of recovered cells was assessed by the ability to form plaques in HT-29 cell
      monolayers and by the ability to colonise mouse spleens. Although the cells were
      classified as avirulent when in the VBNC state, the virulence was recovered after
      resuscitation.

PMID- 17540160
TI  - A spatial hazard model for cluster detection on continuous indicators of disease:
      application to somatic cell score.
AB  - Methods for spatial cluster detection dealing with diseases quantified by
      continuous variables are few, whereas several diseases are better approached by
      continuous indicators. For example, subclinical mastitis of the dairy cow is
      evaluated using a continuous marker of udder inflammation, the somatic cell score
      (SCS). Consequently, this study proposed to analyze spatialized risk and cluster
      components of herd SCS through a new method based on a spatial hazard model. The
      dataset included annual SCS for 34 142 French dairy herds for the year 2000, and
      important SCS risk factors: mean parity, percentage of winter and spring
      calvings, and herd size. The model allowed the simultaneous estimation of the
      effects of known risk factors and of potential spatial clusters on SCS, and the
      mapping of the estimated clusters and their range. Mean parity and winter and
      spring calvings were significantly associated with subclinical mastitis risk. The
      model with the presence of 3 clusters was highly significant, and the 3 clusters
      were attractive, i.e. closeness to cluster center increased the occurrence of
      high SCS. The three localizations were the following: close to the city of Troyes
      in the northeast of France; around the city of Limoges in the center-west; and in
      the southwest close to the city of Tarbes. The semi-parametric method based on
      spatial hazard modeling applies to continuous variables, and takes account of
      both risk factors and potential heterogeneity of the background population. This
      tool allows a quantitative detection but assumes a spatially specified form for
      clusters.

PMID- 17540161
TI  - Opening up the Ivory Tower.
AB  - Big pharma is increasingly looking to academia for new drug leads and
      technologies; meanwhile universities are being forced to look beyond the National
      Institutes of Health (NIH) for funding. This mutual attraction-out-of-necessity
      is helping to forge new bonds between industry and academia.

PMID- 17540162
TI  - Turning back the clock on neurodegeneration.
AB  - Does neuronal loss associated with dementia necessarily impair the ability to
      learn new information and recall old memories? In a recent report in Nature,
      Fischer et al. (2007) show that the ability to learn and remember can be
      reestablished in a mouse model of dementia through either environmental
      enrichment or chronic treatment with an inhibitor of histone deacetylase.

PMID- 17540163
TI  - Chronic lymphocytic leukemia: keeping cell death at bay.
AB  - Chronic lymphocytic leukemia (CLL) is a common adult leukemia caused by abnormal
      accumulation of B cells. Raval et al. (2007) now implicate dowregulation of the
      expression of the kinase DAPK1 both genetically and epigenetically in familial
      and sporadic CLL.

PMID- 17540164
TI  - Stopping ras in its tracks.
AB  - Ras interacts with many downstream effectors that regulate complex cytoplasmic
      signaling networks. In this issue, Gupta et al. (2007) use mouse models of Ras
      mediated tumorigenesis to show that the interaction of Ras with a single isoform
      of phosphatidylinositol 3-kinase (PI3K), called p110alpha (PIK3CA), is critical
      for tumor formation. This result will stimulate re-evaluation of pharmacological
      approaches to target Ras for cancer treatment.

PMID- 17540165
TI  - After hours keeps clock researchers CRYing Overtime.
AB  - Three recent reports, including one in this issue of Cell, reveal that the
      circadian regulator CRY is targeted for degradation by the F box E3 ubiquitin
      ligase FBXL3 (Siepka et al., 2007; Busino et al., 2007; Godinho et al., 2007).
      These studies confirm the importance of targeted protein degradation as a key
      design feature of the mammalian circadian clock.

PMID- 17540166
TI  - Oriented cell divisions and muscle satellite cell heterogeneity.
AB  - Satellite cells are crucial for maintaining muscle homeostasis and for
      regeneration following injury. In this issue, Kuang et al. (2007) reveal that
      muscle satellite cells are a heterogeneous mixture of stem cells and committed
      myogenic progenitors. They show that asymmetric division of stem cells in the
      satellite cell niche is a mechanism for generating these two populations.

PMID- 17540167
TI  - Filling a GAP(DH) in caspase-independent cell death.
AB  - Mitochondrial outer-membrane permeabilization can lead to cell death even without
      activation of caspases. In this issue of Cell, Colell et al. (2007) identify the
      glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase as a potent inhibitor
      of caspase-independent cell death that may allow metabolically active cells to
      survive mitochondrial insult.

PMID- 17540168
TI  - GEFs and GAPs: critical elements in the control of small G proteins.
AB  - Guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs)
      regulate the activity of small guanine nucleotide-binding (G) proteins to control
      cellular functions. In general, GEFs turn on signaling by catalyzing the exchange
      from G-protein-bound GDP to GTP, whereas GAPs terminate signaling by inducing GTP
      hydrolysis. GEFs and GAPs are multidomain proteins that are regulated by
      extracellular signals and localized cues that control cellular events in time and
      space. Recent evidence suggests that these proteins may be potential therapeutic
      targets for developing drugs to treat various diseases, including cancer.

PMID- 17540170
TI  - Extending the host range of Listeria monocytogenes by rational protein design.
AB  - In causing disease, pathogens outmaneuver host defenses through a dedicated
      arsenal of virulence determinants that specifically bind or modify individual
      host molecules. This dedication limits the intruder to a defined range of hosts.
      Newly emerging diseases mostly involve existing pathogens whose arsenal has been
      altered to allow them to infect previously inaccessible hosts. We have emulated
      this chance occurrence by extending the host range accessible to the human
      pathogen Listeria monocytogenes by the intestinal route to include the mouse.
      Analyzing the recognition complex of the listerial invasion protein InlA and its
      human receptor E-cadherin, we postulated and verified amino acid substitutions in
      InlA to increase its affinity for E-cadherin. Two single substitutions increase
      binding affinity by four orders of magnitude and extend binding specificity to
      include formerly incompatible murine E-cadherin. By rationally adapting a single
      protein, we thus create a versatile murine model of human listeriosis.

PMID- 17540169
TI  - Downregulation of death-associated protein kinase 1 (DAPK1) in chronic
      lymphocytic leukemia.
AB  - The heritability of B cell chronic lymphocytic leukemia (CLL) is relatively high;
      however, no predisposing mutation has been convincingly identified. We show that
      loss or reduced expression of death-associated protein kinase 1 (DAPK1) underlies
      cases of heritable predisposition to CLL and the majority of sporadic CLL.
      Epigenetic silencing of DAPK1 by promoter methylation occurs in almost all
      sporadic CLL cases. Furthermore, we defined a disease haplotype, which segregates
      with the CLL phenotype in a large family. DAPK1 expression of the CLL allele is
      downregulated by 75% in germline cells due to increased HOXB7 binding. In the
      blood cells from affected family members, promoter methylation results in
      additional loss of DAPK1 expression. Thus, reduced expression of DAPK1 can result
      from germline predisposition, as well as epigenetic or somatic events causing or
      contributing to the CLL phenotype.

PMID- 17540171
TI  - Proinflammatory stimuli induce IKKalpha-mediated phosphorylation of PIAS1 to
      restrict inflammation and immunity.
AB  - How inflammatory stimuli signal to the nucleus to restrict inflammation is poorly
      understood. Protein inhibitor of activated STAT1 (PIAS1), a transcriptional
      regulator that possesses small ubiquitin-related modifier (SUMO) E3 ligase
      activity, inhibits immune responses by selectively blocking the binding of NF
      kappaB and STAT1 to gene promoters. We report here that PIAS1 becomes rapidly
      phosphorylated on Ser90 residue in response to various inflammatory stimuli.
      Mutational studies indicate that Ser90 phosphorylation is required for PIAS1 to
      repress transcription. Upon TNF treatment, wild-type PIAS1, but not the Ser90A
      mutant, becomes rapidly associated with the promoters of NF-kappaB target genes.
      Furthermore, IKKalpha, but not IKKbeta, interacts with PIAS1 in vivo and mediates
      PIAS1 Ser90 phosphorylation, a process that requires the SUMO ligase activity of
      PIAS1. Our results identify a signaling pathway in which proinflammatory stimuli
      activate the IKKalpha-mediated sumoylation-dependent phosphorylation of PIAS1 for
      the immediate repression of inflammatory gene activation.

PMID- 17540172
TI  - L3MBTL1, a histone-methylation-dependent chromatin lock.
AB  - Distinct histone lysine methylation marks are involved in transcriptional
      repression linked to the formation and maintenance of facultative
      heterochromatin, although the underlying mechanisms remain unclear. We
      demonstrate that the malignant-brain-tumor (MBT) protein L3MBTL1 is in a complex
      with core histones, histone H1b, HP1gamma, and Rb. The MBT domain is structurally
      related to protein domains that directly bind methylated histone residues.
      Consistent with this, we found that the L3MBTL1 MBT domains compact nucleosomal
      arrays dependent on mono- and dimethylation of histone H4 lysine 20 and of
      histone H1b lysine 26. The MBT domains bind at least two nucleosomes
      simultaneously, linking repression of transcription to recognition of different
      histone marks by L3MBTL1. Consistently, L3MBTL1 was found to negatively regulate
      the expression of a subset of genes regulated by E2F, a factor that interacts
      with Rb.

PMID- 17540173
TI  - RF3 induces ribosomal conformational changes responsible for dissociation of
      class I release factors.
AB  - During translation termination, class II release factor RF3 binds to the ribosome
      to promote rapid dissociation of a class I release factor (RF) in a GTP-dependent
      manner. We present the crystal structure of E. coli RF3*GDP, which has a three
      domain architecture strikingly similar to the structure of EF-Tu*GTP. Biochemical
      data on RF3 mutants show that a surface region involving domains II and III is
      important for distinct steps in the action cycle of RF3. Furthermore, we present
      a cryo-electron microscopy (cryo-EM) structure of the posttermination ribosome
      bound with RF3 in the GTP form. Our data show that RF3*GTP binding induces large
      conformational changes in the ribosome, which break the interactions of the class
      I RF with both the decoding center and the GTPase-associated center of the
      ribosome, apparently leading to the release of the class I RF.

PMID- 17540174
TI  - Real-time fluorescence detection of ERAD substrate retrotranslocation in a
      mammalian in vitro system.
AB  - Secretory proteins unable to assemble into their native states in the endoplasmic
      reticulum (ER) are transported back or "retrotranslocated" into the cytosol for
      ER-associated degradation (ERAD). To examine the roles of different components in
      ERAD, one fluorescence-labeled ERAD substrate was encapsulated with selected
      lumenal factors inside mammalian microsomes. After mixing microsomes with
      fluorescence-quenching agents and selected cytosolic proteins, the rate of
      substrate efflux was monitored continuously in real time by the decrease in
      fluorescence intensity as cytosolic quenchers contacted dye-labeled substrates.
      The retrotranslocation kinetics of nonglycosylated pro-alpha factor were not
      significantly altered by replacing all lumenal proteins with only protein
      disulfide isomerase or all cytosolic proteins with only PA700, the 19S regulatory
      particle of the 26S proteasome. Retrotranslocation was blocked by antibodies
      against a putative retrotranslocation channel protein, derlin-1, but not
      Sec61alpha. In addition, pro-alpha factor photocrosslinked derlin-1, but not
      Sec61alpha. Thus, derlin-1 appears to be involved in pro-alpha factor
      retrotranslocation.

PMID- 17540175
TI  - Binding of ras to phosphoinositide 3-kinase p110alpha is required for ras-driven
      tumorigenesis in mice.
AB  - Ras proteins signal through direct interaction with a number of effector enzymes,
      including type I phosphoinositide (PI) 3-kinases. Although the ability of Ras to
      control PI 3-kinase has been well established in manipulated cell culture models,
      evidence for a role of the interaction of endogenous Ras with PI 3-kinase in
      normal and malignant cell growth in vivo has been lacking. Here we generate mice
      with mutations in the Pi3kca gene encoding the catalytic p110alpha isoform that
      block its interaction with Ras. Cells from these mice show proliferative defects
      and selective disruption of signaling from growth factors to PI 3-kinase. The
      mice display defective development of the lymphatic vasculature, resulting in
      perinatal appearance of chylous ascites. Most importantly, they are highly
      resistant to endogenous Ras oncogene-induced tumorigenesis. The interaction of
      Ras with p110alpha is thus required in vivo for certain normal growth factor
      signaling and for Ras-driven tumor formation.

PMID- 17540176
TI  - The tumor suppressor PP2A Abeta regulates the RalA GTPase.
AB  - The serine-threonine protein phosphatase 2A (PP2A) is a heterotrimeric enzyme
      family that regulates numerous signaling pathways. Biallelic mutations of the
      structural PP2A Abeta subunit occur in several types of human tumors; however,
      the functional consequences of these cancer-associated PP2A Abeta mutations in
      cell transformation remain undefined. Here we show that suppression of PP2A Abeta
      expression permits immortalized human cells to achieve a tumorigenic state.
      Cancer-associated Abeta mutants fail to reverse tumorigenic phenotype induced by
      PP2A Abeta suppression, indicating that these mutants function as null alleles.
      Wild-type PP2A Abeta but not cancer-derived Abeta mutants form a complex with the
      small GTPase RalA. PP2A Abeta-containing complexes dephosphorylate RalA at Ser183
      and Ser194, inactivating RalA and abolishing its transforming function. These
      observations identify PP2A Abeta as a tumor suppressor gene that transforms
      immortalized human cells by regulating the function of RalA.

PMID- 17540177
TI  - GAPDH and autophagy preserve survival after apoptotic cytochrome c release in the
      absence of caspase activation.
AB  - In cells undergoing apoptosis, mitochondrial outer-membrane permeabilization
      (MOMP) is followed by caspase activation promoted by released cytochrome c.
      Although caspases mediate the apoptotic phenotype, caspase inhibition is
      generally not sufficient for survival following MOMP; instead cells undergo a
      "caspase-independent cell death" (CICD). Thus, MOMP may represent a point of
      commitment to cell death. Here, we identify glyceraldehyde-3-phosphate
      dehydrogenase (GAPDH) as a critical regulator of CICD. GAPDH-expressing cells
      preserved their clonogenic potential following MOMP, provided that caspase
      activation was blocked. GAPDH-mediated protection of cells from CICD involved an
      elevation in glycolysis and a nuclear function that correlated with and was
      replaced by an increase in Atg12 expression. Consistent with this, protection
      from CICD reflected an increase in and a dependence upon autophagy, associated
      with a transient decrease in mitochondrial mass. Therefore, GAPDH mediates an
      elevation in glycolysis and enhanced autophagy that cooperate to protect cells
      from CICD.

PMID- 17540178
TI  - Asymmetric self-renewal and commitment of satellite stem cells in muscle.
AB  - Satellite cells play a central role in mediating the growth and regeneration of
      skeletal muscle. However, whether satellite cells are stem cells, committed
      progenitors, or dedifferentiated myoblasts has remained unclear. Using Myf5-Cre
      and ROSA26-YFP Cre-reporter alleles, we observed that in vivo 10% of sublaminar
      Pax7-expressing satellite cells have never expressed Myf5. Moreover, we found
      that Pax7(+)/Myf5(-) satellite cells gave rise to Pax7(+)/Myf5(+) satellite cells
      through apical-basal oriented divisions that asymmetrically generated a basal
      Pax7(+)/Myf5(-) and an apical Pax7(+)/Myf5(+) cells. Prospective isolation and
      transplantation into muscle revealed that whereas Pax7(+)/Myf5(+) cells exhibited
      precocious differentiation, Pax7(+)/Myf5(-) cells extensively contributed to the
      satellite cell reservoir throughout the injected muscle. Therefore, we conclude
      that satellite cells are a heterogeneous population composed of stem cells and
      committed progenitors. These results provide critical insights into satellite
      cell biology and open new avenues for therapeutic treatment of neuromuscular
      diseases.

PMID- 17540179
TI  - SnapShot: Pattern-recognition receptors.

PMID- 17540180
TI  - The MISSION! program.

PMID- 17540182
TI  - Beta-blockers do not always reduce perioperative events: check catecholamines
      levels postoperatively.

PMID- 17540184
TI  - May granulocyte colony-stimulating factor induce hypercoagulable state?

PMID- 17540185
TI  - Mortality associated with nesiritide.

PMID- 17540187
TI  - The value of approved therapies for pulmonary arterial hypertension.

PMID- 17540188
TI  - Current concepts in the mechanisms and management of drug-induced QT prolongation
      and torsade de pointes.
AB  - Drug-induced long QT syndrome is characterized by a prolonged corrected QT
      interval (QTc) and increased risk of a polymorphic ventricular tachycardia known
      as torsade de pointes (TdP). We review mechanisms, predispositions, culprit
      agents, and management of this potentially fatal phenomenon. Virtually all drugs
      that prolong QTc block the rapid component of the delayed rectifier current
      (I(kr)). Some drugs prolong QTc in a dose-dependent manner, others do so at any
      dose. Most patients that develop drug-induced TdP have underlying risk factors.
      Female sex is the most common. Implicated drugs include class 1A and III
      antiarrhythmics, macrolide antibiotics, pentamidine, antimalarials,
      antipsychotics, arsenic trioxide, and methadone. Treatment for TdP includes
      immediate defibrillation for hemodynamic instability and intravenous magnesium
      sulfate. Potassium levels should be maintained in the high normal range, and all
      QT prolonging agents must be promptly discontinued.

PMID- 17540189
TI  - Beyond the platelet count: heparin antibodies as independent risk predictors.
AB  - A major potential side effect of heparin is immunogenicity, eliciting antibody
      development to a protein complex comprised of platelet factor 4 and heparin.
      Nevertheless, the clinical implications of heparin antibody positive patients
      remain broad, ranging from no apparent clinical consequences to life-threatening
      arterial and venous thromboemboli. The "Iceberg Model" has been proposed to
      depict this spectrum, with a relatively large population of antibody-positive
      patients forming the base of the iceberg, a smaller population of
      thrombocytopenic patients in the middle and a limited number of patients with
      thrombocytopenia and thrombosis comprising the apex. An underlying assumption of
      this model is that thrombosis occurs only in settings of relative or absolute
      thrombocytopenia. However, several recent studies suggest that antibody formation
      to platelet factor 4/heparin complexes, even in the absence of thrombocytopenia,
      may be associated with thrombotic events. In this review, we summarize these
      data, consider potential mechanisms for thrombosis, and suggest recommendations
      for testing and management of antibody-positive patients.

PMID- 17540190
TI  - Human epicardial adipose tissue: a review.
AB  - We discuss the anatomy, physiology, and pathophysiology of epicardial adipose
      tissue and its relationship to coronary atherosclerosis. Epicardial fat stores
      triglyceride to supply free fatty acids for myocardial energy production and
      produces adipokines. It shares a common embryological origin with mesenteric and
      omental fat. Like visceral abdominal fat, epicardial fat thickness, measured by
      echocardiography, is increased in obesity. Epicardial fat could influence
      coronary atherogenesis and myocardial function because there is no fibrous
      fascial layer to impede diffusion of free fatty acids and adipokines between it
      and the underlying vessel wall as well as the myocardium. Segments of coronary
      arteries lacking epicardial fat or separated from it by a bridge of myocardial
      tissue are protected against the development of atherosclerosis in those
      segments. However, when epicardial fat is totally absent in congenital
      generalized lipodystrophy, coronary atherosclerosis can still occur. Macrophages
      are more numerous and densely packed in the periadventitial fat of human
      atherosclerotic coronary arteries with lipid cores than in that of fibrocalcific
      or nonatherosclerotic coronary arteries. In obese patients with multiple
      cardiovascular risk factors, epicardial fat around atheromatous coronaries
      secretes several proinflammatory cytokines and is infiltrated by macrophages,
      lymphocytes, and basophils. Epicardial adipokine expression in obesity without
      coronary atherosclerosis has not been determined. In nonobese patients,
      epicardial fat around atheromatous coronary arteries expresses proinflammatory
      cytokines but produces either less adiponectin, a vasoprotective adipokine, than
      fat around nonatheromatous coronaries or a similar amount compared with thoracic
      subcutaneous fat. Further studies should be done to test the hypothesis that
      adipokines produced by and released from human epicardial adipose tissue might
      contribute locally to the pathogenesis of coronary atherosclerosis.

PMID- 17540192
TI  - Rationale, design, and baseline characteristics of a randomized trial to assess
      the effect of cholesterol lowering on the progression of aortic stenosis: the
      Aortic Stenosis Progression Observation: Measuring Effects of Rosuvastatin
      (ASTRONOMER) trial.
AB  - BACKGROUND: Aortic stenosis (AS) is a common health problem in the western world.
      Recent studies have suggested that cholesterol lowering may have a salutary
      effect on the progression of AS. The primary objective of the ASTRONOMER study is
      to determine whether patients with AS randomized to rosuvastatin will experience
      less progression in AS severity as measured by aortic transvalvular gradients and
      valve areas. The secondary objectives are to determine the effect of rosuvastatin
      on the rate of cardiac death and aortic valve replacement and to assess the time
      to outcome during a follow-up of 3 to 5 years. METHOD: This is a double-blind
      placebo-controlled study. Patients with mild to moderate AS are randomized to
      receive 40 mg/d of rosuvastatin or placebo. Patients with any clinical indication
      for the use of cholesterol-lowering agents according to the 2000 Canadian
      guidelines are excluded. RESULTS: Recruitment of 272 patients from 23 Canadian
      sites was completed in December 2005. Compared with patients with AS in published
      trials, the patients in the ASTRONOMER study are younger (58.1 +/- 13.6 years),
      have less severe AS (AS jet velocity 3.2 +/- 0.4 m/s), and are composed of a
      great proportion (48.9%) of patients with bicuspid aortic valve. CONCLUSIONS:
      Prevention of the development of severe AS needs to be tested in large randomized
      studies. Recruitment for the ASTRONOMER trial has been completed and results will
      be available at the end of 2008.

PMID- 17540191
TI  - Hypertension Intervention Nurse Telemedicine Study (HINTS): testing a
      multifactorial tailored behavioral/educational and a medication management
      intervention for blood pressure control.
AB  - BACKGROUND: Only 31% of Americans with hypertension have their blood pressure
      (BP) under effective control. We describe a study that tests 3 different
      interventions in a randomized controlled trial using home BP telemedicine
      monitoring. METHODS: A sample of hypertensive patients with poor BP control at
      baseline (N = 600) are randomized to 1 of 4 arms: (1) control group--a group of
      hypertensive patients who receive usual care; (2) nurse-administered tailored
      behavioral intervention; (3) nurse-administered medication management according
      to a hypertension decision support system; (4) combination of the 2
      interventions. The interventions are triggered based on home BP values
      transmitted via telemonitoring devices over standard telephone lines. The
      tailored behavioral intervention involves promoting adherence with medication and
      health behaviors. Patients randomized to the medication management or the
      combined arm have their hypertension regimen changed by the study team using a
      validated hypertension decision support system based on evidence-based
      hypertension treatment guidelines and individualized to patients' comorbid
      illnesses. The primary outcome is BP control: < or = 140/90 mm Hg (nondiabetic)
      and < or = 130/80 mm Hg (diabetics) measured at 6-month intervals over 18 months
      (4 total measurements). CONCLUSIONS: Given the increasing prevalence of
      hypertension and our inability to achieve adequate BP control using traditional
      models of care, testing novel interventions in patients' homes may improve
      access, quality, and outcomes.

PMID- 17540193
TI  - Rationale, design, and methods for the Transplant-Eligible MAnagement of
      Congestive Heart Failure (TMAC) trial: a multicenter clinical outcomes trial
      using nesiritide for TMAC.
AB  - BACKGROUND: Urgent heart transplant candidates classified as United Network for
      Organ Sharing status 1B who require continuous infusions of inotropic agents for
      hemodynamic stability often have hemodynamic, electrical, or multisystem
      decompensation. This multicenter trial will study both traditional safety and
      efficacy parameters and the physiologic mechanisms of benefit of the addition to
      conventional therapy of nesiritide, a recombinant analog of brain-type
      natriuretic peptide, in this population. METHODS: TMAC is a prospective,
      randomized, parallel, multicenter, double-blind, placebo-controlled study in
      patients awaiting heart transplantation who meet United Network for Organ Sharing
      status 1B criteria (N = 120) and receive continuous dobutamine or milrinone
      through a double-lumen central catheter for at least 3 consecutive days before
      randomization. Patients will receive standard care and continuous intravenous
      inotrope therapy plus a 28-day continuous infusion of nesiritide or placebo.
      There will be up to 6 months of follow-up. Primary efficacy end point will be
      days alive after treatment without renal, hemodynamic, or electrical worsening at
      completion. Secondary analyses will evaluate effects on hemodynamics,
      echocardiographic parameters, endogenous brain-type natriuretic peptide levels,
      modification of diet in renal disease-calculated glomerular filtration rate, and
      all-cause and cardiovascular mortality. Two mechanistic substudies will evaluate
      the effect on iohexol-determined glomerular filtration rate and assess changes in
      lung mechanics. CONCLUSION: This investigation will provide key data for clinical
      profiles of heart transplant candidates bound to inotropic support. It will
      investigate the efficacy and safety (especially renal) of nesiritide and provide
      mechanistic insight into benefits of its use for the relief of breathlessness.

PMID- 17540194
TI  - Preventing tomorrow's sudden cardiac death today: part I: Current data on risk
      stratification for sudden cardiac death.
AB  - Accurate and timely prediction of sudden cardiac death (SCD) is a necessary
      prerequisite for effective prevention and therapy. Although the largest number of
      SCD events occurs in patients without overt heart disease, there are currently no
      tests that are of proven predictive value in this population. Efforts in risk
      stratification for SCD have focused primarily on predicting SCD in patients with
      known structural heart disease. Despite the ubiquity of tests that have been
      purported to predict SCD vulnerability in such patients, there is little
      consensus on which test, in addition to the left ventricular ejection fraction,
      should be used to determine which patients will benefit from an implantable
      cardioverter defibrillator. On July 20 and 21, 2006, a group of experts
      representing clinical cardiology, cardiac electrophysiology, biostatistics,
      economics, and health policy were joined by representatives of the US Food and
      Drug administration, Centers for Medicare Services, Agency for Health Research
      and Quality, the Heart Rhythm Society, and the device and pharmaceutical industry
      for a round table meeting to review current data on strategies of risk
      stratification for SCD, to explore methods to translate these strategies into
      practice and policy, and to identify areas that need to be addressed by future
      research studies. The meeting was organized by the Duke Center for the Prevention
      of SCD at the Duke Clinical Research Institute and was funded by industry
      participants. This article summarizes the presentations and discussions that
      occurred at that meeting.

PMID- 17540195
TI  - Preventing tomorrow's sudden cardiac death today: part II: Translating sudden
      cardiac death risk assessment strategies into practice and policy.
AB  - Although current evidence supporting a more precise strategy for identifying
      patients at highest risk for sudden cardiac death (SCD) is sparse, strategies for
      translating existing and future evidence into clinical practice and policy are
      needed today. A great many unanswered questions exist. Examples include the
      following: At what level of risk for SCD should we pursue further testing or
      therapy? How should clinical strategies ethically and economically balance
      alternative outcomes? How can we best translate optimal strategies into clinical
      practice so as to prevent tomorrow's SCDs? On July 20 and 21, 2006, a group of
      individuals with expertise in clinical cardiovascular medicine, biostatistics,
      economics, and health policy was joined by government (Food and Drug
      Administration; Centers for Medicare and Medicaid Services; National Heart, Lung,
      and Blood Institute; Agency for Healthcare Research and Quality), professional
      societies (Heart Rhythm Society), and industry to discuss strategies for risk
      assessment and prevention of SCD. The meeting was organized by the Duke Center
      for the Prevention of Sudden Cardiac Death and the Duke Clinical Research
      Institute. This article, the second of 2 documents, summarizes the policy
      discussions of that meeting, discusses an analytic framework for evaluating the
      risks and benefits associated with SCD prevention and risk stratification, and
      addresses the translation of SCD risk assessment strategies into practice and
      policy.

PMID- 17540196
TI  - Interactions between heparins, glycoprotein IIb/IIIa antagonists, and coronary
      intervention. The Global Registry of Acute Coronary Events (GRACE).
AB  - OBJECTIVES: The purpose of this study is to evaluate hospital mortality and major
      bleeding rates among patients receiving low molecular weight heparin (LMWH),
      unfractionated heparin (UFH), or both, and to investigate whether concomitant
      glycoprotein (GP) IIb/IIIa antagonists and coronary intervention affect patterns
      of use and outcomes with different heparins. BACKGROUND: With widespread use of
      glycoprotein (GP) IIb/IIIa inhibitors and invasive treatments, patients with high
      risk acute coronary syndrome (ACS) may have a greater bleeding risk and may not
      gain additional benefit from LMWHs. The purpose of this study is to evaluate
      hospital mortality and major bleeding rates among patients receiving LMWH, UFH,
      or both, and to investigate whether concomitant GP IIb/IIIa antagonists and
      coronary intervention affect patterns of use and outcomes with different
      heparins. METHODS: Data were analyzed from 28,445 patients with ACS; 21,287 had
      non-ST-segment elevation myocardial infarction or unstable angina and received
      LMWH or UFH. RESULTS: Fifty-one percent of patients received LMWH, 32% UFH, and
      17% both. The lowest inhospital mortality and bleeding rates occurred with LMWH
      (2.7% and 1.8% vs UFH, 4.1% and 2.7%; all P < .0001). After multivariable
      analysis, LMWH was associated with lower inhospital mortality rates in patients
      not treated with GP IIb/IIIa antagonists, irrespective of whether they had a
      percutaneous coronary intervention (PCI) (odds ratio 0.77, 95% confidence
      interval 0.63-0.94 without PCI vs odds ratio 0.45, 95% confidence interval 0.21
      0.98 with PCI). Excess bleeding occurred with PCI in LMWH-treated patients.
      Patients older than 75 years who received GP IIb/IIIa antagonists and any
      antithrombotic but not PCI had an increased risk of major bleeding (LMWH 14%, UFH
      8.3%). CONCLUSIONS: In patients with non-ST-elevation ACS without GP IIb/IIIa
      antagonists, LMWH was associated with a lower mortality rate and more bleeding
      episodes in PCI-treated patients than UFH; no differences occurred with GP
      IIb/IIIa antagonists. Elderly patients managed medically with GP IIb/IIIa
      antagonists and either heparin had a very high major bleeding risk.

PMID- 17540197
TI  - Sex-specific effects of diabetes on adverse outcomes after percutaneous coronary
      intervention: trends over time.
AB  - BACKGROUND: Diabetes is a stronger risk factor for coronary heart disease in
      women than in men. Whether diabetes also poses greater risks to women after
      percutaneous coronary intervention (PCI) has not been examined. METHODS: We
      examined 20586 PCI procedures at Emory University Hospitals (Atlanta, GA) between
      1990 and 2003. Hazard ratios (HRs) for 1-year major adverse cardiac events were
      calculated comparing diabetic with nondiabetic patients by sex and study year.
      Data were adjusted for demographic and clinical factors using Cox proportional
      hazards models. RESULTS: Despite increasing patient age and comorbidity burden,
      diabetic and nondiabetic men had a significant improvement in PCI outcomes
      between 1990 and 2003 (P < .001). Diabetic women also tended to have improved PCI
      outcomes over time (P = .073), but not nondiabetic women (P = .206). Overall,
      diabetes had a stronger association with adverse outcomes in women (HR 1.93, 95%
      CI 1.55-2.40) than in men (HR 1.26, 95% CI 1.09-1.47) (P = .002 for the
      interaction between sex and diabetes). The excess risk associated with diabetes
      in women, however, was largely driven by early study years (1990-1993). This
      excess risk associated with diabetes in women declined over time, and diabetes
      had a similar effect on outcomes in both women and men in more recent years (P =
      .010 for the interaction between sex, diabetes, and time). CONCLUSIONS:
      Percutaneous coronary intervention outcomes of diabetic and nondiabetic men have
      improved in recent years. However, among women, diabetic patients had greater
      improvements in outcomes after PCI compared with nondiabetic patients. As a
      result, diabetes is no longer a stronger risk factor for adverse outcomes after
      PCI in women than in men.

PMID- 17540198
TI  - Randomized comparison of dexamethasone-eluting stents with bare metal stent
      implantation in patients with acute coronary syndrome: serial angiographic and
      sonographic analysis.
AB  - AIMS: The aim of this study is to compare the anti-inflammatory effect of the
      dexamethasone preloaded stent (Dexamet, Abbott, Galway, Ireland) with the bare
      metal stent (BMS; BiodivYsio, Biocompatibles Cardiovascular LTD, Galway, Ireland)
      in patients with acute coronary syndrome (ACS) assessed by angiographic (QCA) and
      intracoronary ultrasound (ICUS). METHODS AND RESULTS: One hundred twenty patients
      with ACS were randomly assigned to revascularization using the Dexamet stent (n =
      60) or BMS (n = 60). Serial QCA analysis and ICUS analysis were performed during
      long-term follow-up (2.9 F; 20 MHz transducer; Volcano Corp, Brussels, Belgium).
      Power calculations were performed for QCA-derived differences of lumen loss. In
      addition, statistical analysis was performed (SPSS for Windows 12.0.1). The
      target lesion revascularization rate was lower in the Dexamet group (10 [16.67%]
      vs 20 [33.33%] patients; P = .031). The QCA revealed improved lumen restoration
      in the Dexamet stent group (lumen loss, 0.55 +/- 0.65 vs 1.07 +/- 0.92 mm [P =
      .001]; loss index, 0.20 +/- 0.23 vs 0.46 +/- 0.42 [P < .001]). The ICUS revealed
      greater neointimal proliferation in the BMS versus the Dexamet stent group (3.36
      +/- 1.03 vs 3.05 +/- 1.38 mm2; P < .001). Death (n = 1) and the number of total
      occlusions of the stent segment (n = 1) were identical in both groups.
      CONCLUSION: Dexamet stents, in comparison with the BMS stents, reduced the target
      lesion revascularization rate in patients with ACS and lead to better lumen
      restoration during long-term follow-up.

PMID- 17540199
TI  - Secondary prevention outcomes among black and white cardiac rehabilitation
      patients.
AB  - BACKGROUND: Disparities in coronary heart disease and related risk factors
      persist. It is unknown if cardiac rehabilitation (CR) narrows the gap in risk
      factor control between black and white patients. Thus, we compared baseline
      characteristics and secondary prevention outcomes between black and white CR
      patients. METHODS: Data from patient records (n = 616, mean age 62 +/- 10 years,
      29% women, 25% black) collected between January 1996 and June 2006 were examined.
      Comparisons were made between Blacks and Whites for baseline characteristics,
      changes in secondary prevention measures during CR, and the proportion of
      patients at treatment goals before and after CR. General linear regression
      modeling was used to determine the effect of race/ethnicity on outcomes. RESULTS:
      At baseline, Blacks had more hypertension and diabetes and more adverse measures
      for blood pressure, low-density lipoprotein and non-high-density lipoprotein
      cholesterol (non-HDL-C), hemoglobin A1c, 6-minute walk distance, and Short-Form
      Health Survey (SF-36) physical component score. At CR completion, improvement (P
      < .05) was achieved among whites in all measures except for HDL-C and systolic
      blood pressure. Among Blacks, improvement did not reach significance for HDL-C,
      body mass index, waist circumference, and hemoglobin A1c (when diabetes was
      present). When adjusting for age, gender, number of sessions attended, and
      baseline measure, Whites improved more than Blacks in 6-minute walk distance,
      self-reported physical activity, body mass index, waist circumference, low
      density lipoprotein cholesterol, and hemoglobin A1c (all P < .05). CONCLUSION:
      Blacks entered CR with more adverse risk factor measures compared with Whites.
      Although both groups gained secondary prevention benefits, the degree of
      improvement was less for Blacks than Whites, and this was especially evident
      among black women.

PMID- 17540200
TI  - Elevated vascular endothelial growth factor levels are associated with
      aortopulmonary collateral vessels in patients before and after the Fontan
      procedure.
AB  - BACKGROUND: Aortopulmonary collaterals (APCs) are frequently observed before and
      after the Fontan procedure. However, the mechanism of the development of APCs is
      unknown. We hypothesized that one or several antiangiogenic and/or angiogenic
      growth factors might play a role in the development of APCs. METHODS: Eighty-five
      patients were enrolled and divided into 3 groups (Fontan group: 30 patients after
      the Fontan procedure, cyanotic group: 29 patients with cyanotic heart disease,
      and control group: 26 patients with cyanotic heart disease after biventricular
      repair). We measured basic fibroblast growth factor, vascular endothelial growth
      factor (VEGF), hepatocyte growth factor, and endostatin at catheterization.
      Angiographic evaluation for the presence of APCs using a 4-point scale (grade 1:
      absent APCs, > or = grade 2: significantly present APCs) was performed, and the
      relation of the serum levels of these factors to the presence of APCs was
      assessed. RESULTS: The grade of APCs significantly increased in the Fontan group,
      but it decreased in the control group. The serum VEGF levels were higher in the
      Fontan group (280 +/- 174 pg/mL) and the cyanotic group (302 +/- 245 pg/mL) than
      in the control group (111 +/- 91 pg/mL) (P = .0004), and they were higher in
      patients with APCs (383 +/- 204 pg/mL) than in those without APCs (115 +/- 65
      pg/mL) (P < .0001). There was no significant difference in the serum basic
      fibroblast growth factor, hepatocyte growth factor, and endostatin levels between
      the 3 groups. CONCLUSIONS: Aortopulmonary collaterals increase after the Fontan
      procedure. Serum VEGF levels are associated with the presence of APCs. Vascular
      endothelial growth factor may play a role in the development of APCs in patients
      with cyanotic heart disease and after the Fontan procedure.

PMID- 17540201
TI  - Long-term patency of internal thoracic artery grafts for coronary artery stenosis
      due to Kawasaki disease: comparison of early with recent results in small
      children.
AB  - BACKGROUND: The results of coronary artery bypass grafting using the internal
      thoracic artery (ITA) had been reported less satisfactory in patients < 12 years
      old with coronary artery lesions caused by Kawasaki disease. METHODS: Since 1983,
      67 patients have undergone this operation in our hospital; their age at operation
      ranged from 1 to 59 years (median 11 years), and the total number of ITA grafts
      was 95. The interval from operation to latest graft patency as confirmed by
      angiogram or echocardiogram ranged from 4 months to 23 years (median 8 years).
      For analysis of graft patency rates, patients were divided into 4 groups based on
      year of coronary artery bypass grafting and age when grafted. The groups based on
      year were from 1983 to 1993 (early) and from 1994 to 2006 (later), whereas the
      age groups were age at operation < 12 years and age at operation > or = 12 years.
      From 1999, percutaneous transluminal balloon angioplasty was performed for
      postoperative anastomotic stenosis. RESULTS: Percutaneous transluminal balloon
      angioplasty for anastomotic stenosis in ITA graft was performed in 6 patients.
      When the age at operation was < 12 years, the 10-year patency rate in the later
      period was 94.4% (n = 18), significantly > the 70.0% (n = 30) seen in the earlier
      period (P < .05). CONCLUSION: Recent results of ITA grafts in patients < 12 years
      old have improved through the application of appropriate indications and
      percutaneous transluminal balloon angioplasty for anastomotic stenosis. Once good
      flow in the ITA 1 year after surgery is confirmed, graft patency will persist >
      20 years.

PMID- 17540202
TI  - Association between cardiorespiratory fitness and prevalence of carotid
      atherosclerosis among men with hypertension.
AB  - BACKGROUND: Carotid atherosclerosis is a risk factor for cardiovascular mortality
      and may represent hypertension-related target organ damage. Cardiorespiratory
      fitness is inversely associated with cardiovascular mortality in hypertensive
      men. We tested the hypothesis that higher levels of cardiorespiratory fitness are
      inversely associated with the prevalence of carotid atherosclerosis in a cross
      sectional study of 2532 (53.2 +/- 8.5 years old) hypertensive men. METHODS: Men
      with hypertension (defined as systolic over diastolic blood pressure of > or =
      140/90 mm Hg or self-reported use of antihypertensive medication) underwent
      maximal exercise treadmill testing with expired gas analysis. Carotid
      atherosclerosis was defined as stenosis of > 25% and/or intima-media thickness of
      > 1.2 mm using B-mode ultrasonography. RESULTS: The overall prevalence of carotid
      atherosclerosis was 13.4%. The prevalence of carotid atherosclerosis was
      inversely associated with cardiorespiratory fitness category (low 22.5%, moderate
      10.9%, and high 8.7%; P < .001 for trend). After adjusting for established risk
      factors, high and moderate fitness were associated with lower odds ratios for
      having carotid atherosclerosis, 0.63 (95% CI 0.47-0.85) and 0.62 (95% CI 0.41
      0.92), respectively, compared with low fitness. Each metabolic equivalent
      increment higher peak oxygen uptake was associated with 11% (odds ratio 0.89, 95%
      CI 0.82-0.97) lower prevalence of carotid atherosclerosis. CONCLUSIONS: These
      results suggest that higher levels of cardiorespiratory fitness are inversely
      associated with the prevalence of carotid atherosclerosis in hypertensive men.

PMID- 17540203
TI  - Guideline-adherent antithrombotic treatment is associated with improved outcomes
      compared with undertreatment in high-risk patients with atrial fibrillation. The
      Euro Heart Survey on Atrial Fibrillation.
AB  - BACKGROUND: The Euro Heart Survey showed that antithrombotic treatment in
      patients with atrial fibrillation (AF) was moderately tailored to the 2001
      American College of Cardiology, American Heart Association, and European Society
      of Cardiology (ACC/AHA/ESC) guidelines for the management of AF. What
      consequences does guideline-deviant antithrombotic treatment have in daily
      practice? METHODS: In the Euro Heart Survey on AF (2003-2004), an observational
      study on AF care in European cardiology practices, information was available on
      baseline stroke risk profile and antithrombotic drug treatment and on
      cardiovascular events during 1-year follow-up. Antithrombotic guideline adherence
      is assessed according to the 2001 ACC/AHA/ESC guidelines. Multivariable logistic
      regression was performed to assess the association of guideline deviance with
      adverse outcome. RESULTS: The effect of antithrombotic guideline deviance was
      analyzed exclusively in 3634 high-risk patients with AF because these composed
      the majority (89%) and because few cardiovascular events occurred in low-risk
      patients. Among high-risk patients, antithrombotic treatment was in agreement
      with the guidelines in 61% of patients, whereas 28% were undertreated and 11%
      overtreated. Compared to guideline adherence, undertreatment was associated with
      a higher chance of thromboembolism (odds ratio [OR], 1.97; 95% CI, 1.29-3.01; P =
      .004) and the combined end point of cardiovascular death, thromboembolism, or
      major bleeding (OR, 1.54; 95% CI, 1.14-2.10; P = .024). This increased risk was
      nonsignificant for the end point of stroke alone (OR, 1.42; 95% CI, 0.82-2.46; P
      = .170). Overtreatment was nonsignificantly associated with a higher risk for
      major bleeding (OR, 1.52; 95% CI, 0.76-3.02; P = .405). CONCLUSIONS:
      Antithrombotic undertreatment of high-risk patients with AF was associated with a
      worse cardiovascular prognosis during 1 year, whereas overtreatment was not
      associated with a higher chance for major bleeding.

PMID- 17540204
TI  - Prognostic role of transesophageal echocardiography in acute type A aortic
      dissection.
AB  - BACKGROUND: Acute type A aortic dissection (AAD) remains a highly lethal entity
      for which emergent surgical correction is standard care. Prior studies have
      identified specific clinical findings as being predictive of outcome. The
      prognostic significance of specific findings on imaging studies is less well
      described. We sought to identify the prognostic value of transesophageal
      echocardiography (TEE) in medically and surgically treated patients with AAD.
      METHODS: We studied 522 AAD patients enrolled over 6 years in the International
      Registry of Acute Aortic Dissection who underwent TEE. Multivariate analysis
      identified independent associations of inhospital mortality, first using clinical
      variables (model 1), after which TEE data were added to build a final model
      (model 2). RESULTS: Inhospital mortality was 28.7%. Transesophageal
      echocardiographic evidences of pericardial effusion (P = .04), tamponade (P <
      .01), periaortic hematoma (P = .02), and patent false lumen (P = .08) were more
      frequent in nonsurvivors. Dilated ascending aorta (P = .03), dissection localized
      to the ascending aorta (P = .02), and thrombosed false lumen (P = .08) were less
      common in nonsurvivors. Model 1 identified age > or = 70 years, any pulse
      deficit, renal failure, and hypotension/shock as independent predictors of death.
      Model 2 identified dissection flap confined to ascending aorta (odds ratio 0.2,
      95% CI 0.1-0.6) and complete thrombosis of false lumen (odds ratio 0.15, 95% CI
      0.03-0.86) as protective. In the medically treated group, mortality was 31% for
      subjects with a partially or completely thrombosed false lumen versus 66% in the
      presence of a patent false lumen. CONCLUSIONS: Transesophageal echocardiography
      provides prognostic information in AAD beyond that provided by clinical risk
      variables.

PMID- 17540205
TI  - Temporal trends in clinical characteristics, treatments, and outcomes for heart
      failure hospitalizations, 2002 to 2004: findings from Acute Decompensated Heart
      Failure National Registry (ADHERE).
AB  - BACKGROUND: The purpose of this study was to assess temporal trends in clinical
      characteristics, treatments, quality indicators, and outcomes for heart failure
      (HF) hospitalizations. METHODS: Characteristics, treatments, quality measures,
      and inhospital outcomes were measured over 12 consecutive quarters (January 2002
      to December 2004) using data from 159,168 enrollments from 285 ADHERE hospitals.
      RESULTS: Baseline characteristics were similar or showed only modest changes, and
      severity of illness by logistic regression was unchanged over all 12 quarters.
      Inhospital treatment changed significantly over time with inotrope use decreasing
      from 14.7% to 7.9% (P < .0001). Discharge instructions increased 133%; smoking
      counseling, 132%; left ventricular function measurement, 8%; and beta-blocker
      use, 29% (all P < .0001). Clinical outcomes improved over time, including need
      for mechanical ventilation, which decreased 5.3% to 3.4% (relative risk 0.64, P <
      .0001); length of stay (mean), 6.3 to 5.5 days; and mortality, 4.5% to 3.2%
      (relative risk 0.71, P < .0001). CONCLUSIONS: Over a 3-year period, demographics
      and clinical characteristics were relatively similar, but significant changes in
      intravenous therapy, enhancements in conformity to quality-of-care measures,
      increased administration of evidence-based HF medications, and substantial
      improvements in inhospital morbidity and mortality were observed during
      hospitalization for HF.

PMID- 17540206
TI  - Beta-blocker dosing in community-based treatment of heart failure.
AB  - BACKGROUND: Community patients with heart failure (HF) are older, less often
      treated by HF specialists, and have more comorbidity than those in randomized
      clinical trials. These differences might affect beta-blocker prescribing in HF.
      METHODS: To explore patterns of beta-blocker prescribing for HF in the community
      and their association with outcomes, we determined carvedilol doses at end
      titration in 4113 patients from a community-based beta-blocker HF registry
      according to physician and patient characteristics, HF severity, and rates of
      hospitalization and death. RESULTS: Female sex, age > or = 65 years, and left
      ventricular ejection fraction > or = 35% were associated with lower beta-blocker
      doses. Average daily dose of beta-blocker was lower with worse baseline New York
      Heart Association class. More patients of cardiologists achieved carvedilol doses
      > or = 25 mg twice daily, whereas in those of noncardiologists lower doses were
      more common. Relative risk of HF hospitalizations or all-cause death was
      significantly lower with higher doses of beta-blocker. CONCLUSIONS: Beta-blocker
      dosing in community HF appears lower than in randomized clinical trials,
      especially when prescribed by noncardiologists. At all doses, patients taking the
      beta-blocker carvedilol have a lower incidence of death and HF hospitalization
      than those discontinuing it, regardless of physician type in the community
      setting.

PMID- 17540207
TI  - A meta-analysis of trials of pulmonary hypertension: a clinical condition looking
      for drugs and research methodology.
AB  - BACKGROUND: Various innovative pharmacologic strategies for the treatment of
      patients with pulmonary hypertension have been tested in recent years. Neither
      their comparative efficacy on surrogate end points nor the overall impact on
      mortality have been formally reviewed. METHODS: We did a systematic overview of
      all randomized trials on the therapeutic yield of prostacyclin and analogues,
      endothelin receptor antagonists, and phosphodiesterase type 5 inhibitors in
      patients with pulmonary hypertension searched in EMBASE, MEDLINE, and CINAHL
      databases from January 1985 to December 2005. RESULTS: Sixteen trials involving
      1962 patients met the inclusion criteria. Up to 80% of the patients were in
      functional class III/IV with a median walking distance of 330 m at baseline.
      Overall, experimental treatments were associated with (1) a nonsignificant
      reduction in all-cause mortality (relative risk 0.70, 95% CI 0.41-1.22), (2) a
      minor but statistically significant improvement in exercise capacity of 42.8 m
      (95% CI 27.8-57.8), and (3) an improved dyspnea status by at least one functional
      class (relative risk 1.83, 95% CI 1.26-2.66). Changes in exercise capacity were
      not found to be predictive of a survival benefit. CONCLUSIONS: Although
      confirming the limited benefits in clinical end points documented by each trial,
      the overview fails to support a significant survival advantage and does not
      support the predictive power of surrogate end points.

PMID- 17540208
TI  - Relationship of high-sensitivity C-reactive protein to prognosis and other
      prognostic markers in outpatients with heart failure.
AB  - BACKGROUND: Inflammatory markers are increased in chronic heart failure (CHF),
      including high-sensitivity C-reactive protein (hsCRP), but there is little
      information on its relationship to prognosis or other prognostic markers. We
      aimed to investigate the relationship between hsCRP and prognosis in patients
      with CHF and left ventricular systolic dysfunction (LVSD). METHODS: Patients with
      CHF and LVSD (n = 957), but without infection or inflammatory disease, were
      identified. Patients had their medical history taken, underwent physical
      examination, had electrocardiographic and echocardiographic assessment, and had a
      6-minute corridor walk test (6MWT) and blood tests, including hsCRP and N
      terminal pro-B natriuretic peptide (NT-pro-BNP). RESULTS: Patients with worse New
      York Heart Association class (P = .02), shorter 6-minute corridor walk test
      distance (P < .001), higher NT-pro-BNP levels (P < .001), anemia (P < .001), and
      renal dysfunction (P < .001), but not lower LV ejection fraction, had higher
      plasma concentrations of hsCRP. Patients with a CRP of >11.0 pg/mL had a hazard
      ratio for death of 3.0 compared with those with a CRP of <2.8 pg/mL (P < .001).
      Of 402 patients who had a second sample taken for hsCRP at 1 year, 46% showed a
      substantial change from baseline levels. Marked increases in hsCRP were
      associated with a fall in hemoglobin level. NT-pro-BNP was noted to be a more
      accurate prognostic marker than hsCRP (area under the curve of 0.74 compared with
      0.67 for hsCRP, P < .05). CONCLUSION: Patients with CHF and LVSD have increased
      serum concentrations of hsCRP that are related to functional limitation and
      prognosis but not to the severity of LV ejection fraction.

PMID- 17540209
TI  - Long-term effect of atorvastatin on neurohumoral activation and cardiac function
      in patients with chronic heart failure: a prospective randomized controlled
      study.
AB  - BACKGROUND: Statins have pleiotropic effects, such as improvement in endothelial
      function and antiinflammatory, antiproliferative, and antioxidative effects, that
      should be beneficial for patients with chronic heart failure (CHF). The aim of
      this study was to investigate the long-term effect of statins on neurohumoral
      activation and cardiac function in patients with CHF. METHODS: We enrolled 38
      outpatients with mild to moderate CHF and radionuclide left ventricular ejection
      fraction (LVEF) <40%. These patients were randomly assigned to receive
      atorvastatin (10 mg/d) or conventional treatment for heart failure and were
      prospectively followed up for at least 3 years. At entry, we measured plasma
      concentrations of brain natriuretic peptides (BNPs) and left ventricular end
      diastolic dimension and LVEF by echocardiography; thereafter, these measurements
      were repeated at least every 6 months. The primary end point was defined as the
      improvement in cardiac function and BNP. RESULTS: There were no significant
      differences in age, sex, New York Heart Association class, left ventricular end
      diastolic dimension, LVEF, and serum cholesterol level at entry between patients
      with (n = 19) and without atorvastatin (control, n = 19). After a follow-up
      period of 31 +/- 14 months, BNP (median [25th, 75th percentile]) significantly
      decreased in the atorvastatin group (84 [36, 186] to 55 [37, 91] pg/mL, P = .02)
      but not in the control group. Left ventricular end-diastolic dimension
      significantly decreased (67.1 [59.9, 70.8] to 61.1 [58, 63.9] mm, P = .02), and
      LVEF also significantly increased in the atorvastatin group (33.3% +/- 7.4% to
      39.1% +/- 12.1%, P = .01) but not in the control group. CONCLUSION: Long-term
      atorvastatin therapy decreases neurohumoral activation and improves cardiac
      function in patients with mild to moderate CHF.

PMID- 17540210
TI  - Effects of exercise training on heart rate recovery in patients with chronic
      heart failure.
AB  - BACKGROUND: Heart rate recovery (HRR) is a marker of vagal tone that is
      associated with survival, but little is known about the effects of exercise
      training on HRR in patients with heart failure (HF). METHODS: Twenty-four
      patients with HF were randomized to a 2-month residential rehabilitation program
      or to usual care. Symptom-limited exercise testing was performed at baseline and
      at discharge from the program. Heart rate recovery was expressed as the decline
      in heart rate from peak exercise through 6 minutes into recovery. In addition,
      HRR recovery curves were normalized to a range of 1 at peak heart rate and 0 at 6
      minutes and adjusted for differences in heart rate reserve, facilitating the
      comparison of recovery curve shapes between groups. RESULTS: Mean peak oxygen
      uptake and oxygen uptake at the lactate threshold increased 26% (P < .05) and 39%
      (P < .001), respectively, in the exercise group, whereas neither of these
      responses changed significantly among controls. Heart rate recovery was
      significantly more rapid in the exercise group after training (main effect 12.6
      vs 2.6 beat/min in the trained and control groups, respectively, P = .005). The
      normalized curves showed that the largest improvement in recovery curve shape
      occurred in the exercise group, but most of the HRR improvement was accounted for
      by a widening of the difference between peak and resting heart rate. CONCLUSION:
      Exercise training results in a faster HRR in patients with HF. Heart rate
      recovery, as a simple marker of autonomic function, is an easily acquired
      response that may be useful for evaluating patient outcomes in cardiac
      rehabilitation.

PMID- 17540211
TI  - Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in
      patients with congestive heart failure and chronic kidney disease.
AB  - BACKGROUND: Patients with coexistent heart failure and chronic kidney disease
      (CKD) have a poor prognosis, possibly related to the underuse of standard medical
      therapies--angiotensin-converting enzyme inhibitors (ACE-I) and angiotensin
      receptor blockers (ARB). METHODS: We performed a retrospective analysis of the
      Minnesota Heart Survey, identifying patients hospitalized in 2000 in the
      Minneapolis-St Paul metropolitan area with heart failure. The main outcome
      measure was the association of ACE-I and ARB use on 30-day and 1-year mortality,
      stratified by glomerular filtration rate (GFR). RESULTS: Compared to patients
      with heart failure with preserved renal function (GFR > or = 90 mL/min), patients
      with severely impaired renal function (GFR <15 mL/min) were far less likely to
      receive ACE-I or ARB during hospitalization (52.0% vs 69.5%, P < .0001) or at
      discharge (50.5% vs 65.1%, P < .0001). Worsening renal function was associated
      with increased mortality, both at 30 days and at 1 year. The inhospital use of
      either an ACE-I or ARB was associated with significantly reduced 30-day mortality
      (OR 0.45, 95% CI 0.28-0.59) after adjusting for multiple risk factors. Similarly,
      the discharge prescription of either an ACE-I or ARB was associated with a
      significant reduction in adjusted 1-year mortality (OR 0.72, 95% CI 0.58-0.91).
      However, among patients on dialysis, there was no benefit of ACE-I or ARB on
      either 30-day or 1-year mortality. CONCLUSIONS: Angiotensin-converting enzyme
      inhibitors and ARB are underused in patients with heart failure with chronic
      kidney disease. Given the reduction in 30-day and 1-year mortality, these
      medications should be considered in most patients with heart failure, independent
      of underlying renal function. Among patients on hemodialysis, further
      investigation is warranted.

PMID- 17540212
TI  - Relation of sex to morbidity and mortality in patients with heart failure and
      reduced or preserved left ventricular ejection fraction.
AB  - BACKGROUND: Previous studies indicate a survival advantage for women over men
      with chronic heart failure associated with reduced or preserved ejection
      fraction. Whether women with chronic heart failure are at less risk for
      hospitalization for worsening heart failure has not been well investigated.
      METHODS: Using data from the DIG trial, the relationship between sex and adverse
      outcomes, especially the risk of hospitalization for various causes, was
      evaluated in patients with reduced or preserved left ventricular ejection
      fraction. RESULTS: Survival was worse for men than women with either reduced (HR
      1.48, 95% CI 1.33-1.65, P < .001) or preserved ejection fraction (HR 1.60, 95% CI
      1.20-2.13, P = .001), with P =.406 for sex interaction. In contrast, the risk of
      hospitalization for heart failure was greater in men than women when ejection
      fraction was reduced (HR 1.19, 95% CI 1.07-1.33, P = .001) but not preserved (HR
      0.90, 95% CI 0.67-1.22, P = .494), with P = .003 for sex interaction. The
      relative risk of hospitalization for worsening failure between reduced and
      preserved ejection fraction was greater in men than women (HR 5.97, 95% CI 1.40
      25.56, P = .001 in men vs HR 2.65, 95% CI 0.68-10.31, P = .159 in women).
      CONCLUSION: A survival advantage for women was seen in heart failure with reduced
      or preserved ejection fraction. In contrast, women appeared to be at lower risk
      for hospitalization for heart failure only when left ventricular systolic
      dysfunction was present.

PMID- 17540213
TI  - Relation of early improvement in coronary flow reserve to late recovery of left
      ventricular function after beta-blocker therapy in patients with idiopathic
      dilated cardiomyopathy.
AB  - BACKGROUND: Beta-blocker therapy reverses left ventricular (LV) remodeling in
      patients with idiopathic dilated cardiomyopathy (IDC). Improvement in coronary
      circulation by beta-blocker could play a role in these circumstances. This study
      investigated the relationship between change in coronary flow reserve (CFR), as a
      marker of coronary circulation, and subsequent improvement in LV ejection
      fraction (LVEF) at follow-up during carvedilol therapy in patients with IDC.
      METHODS: Eighteen patients with IDC underwent CFR measurements by transthoracic
      Doppler echocardiography at baseline and after 1 month of treatment with
      carvedilol. A follow-up echocardiographic assessment of LVEF was done at 12 +/- 6
      months of treatment. The patients were classified by the degree of improvement in
      LVEF in the follow-up study, as group A (LVEF change > or = 10%) and group B
      (LVEF change < 10%). RESULTS: Although there was no significant difference in CFR
      between the 2 groups at baseline, CFR was significantly higher in group A than in
      group B at 1 month of therapy (3.7 +/- 0.5 vs 2.5 +/- 0.9; P < .01). Coronary
      flow reserve change after 1 month was significantly greater in group A than in
      group B (1.3 +/- 0.6 vs 0.4 +/- 0.5; P < .01). Logistic regression analysis
      revealed that CFR change predicted a significant improvement in LVEF at follow-up
      (P < .05). Furthermore, a significant correlation was found between the change in
      CFR after 1 month and that in LVEF on follow-up (r = 0.65, P < .01). CONCLUSIONS:
      This study demonstrated that early change in CFR is associated with subsequent
      improvement in LVEF, suggesting the potential predictive value of coronary
      circulation for subsequent LV reverse remodeling after beta-blocker therapy in
      patients with IDC.

PMID- 17540214
TI  - Coronary endothelial dysfunction and hyperlipidemia are independently associated
      with diastolic dysfunction in humans.
AB  - BACKGROUND: Coronary endothelial dysfunction (CED) and DHF are both associated
      with myocardial ischemia and CAD risk factors. The objective of the this study
      was to determine if CED and CAD factors are associated with diastolic dysfunction
      before the development of occlusive CAD or clinical heart failure. METHODS:
      Patients with normal ejection fraction and nonocclusive CAD who underwent
      coronary endothelial function studies were identified. Left ventricular
      relaxation was assessed by tissue Doppler assessment of early diastolic ascent of
      the septal mitral annulus (Ea). Multiple linear regression was used to
      investigate whether coronary risk factors influenced diastolic function after
      adjusting for the presence of CED. RESULTS: A total of 160 patients had adequate
      assessment of diastolic relaxation. With multiple linear regression models,
      %deltaCBF (P = .018) was associated with a higher Ea; in contrast, older age (P <
      .001), female sex (P = .028), higher left ventricular mass index (P = .016), and
      higher nonhigh-density lipoprotein cholesterol (P = .022) were associated with a
      lower Ea. CONCLUSION: Coronary endothelial dysfunction and hyperlipidemia are
      independently associated with impaired relaxation in patients with normal
      ejection fraction in the absence of occlusive CAD and heart failure. The current
      study suggests a new potential mechanism for the development of endothelial and
      diastolic dysfunction in humans.

PMID- 17540215
TI  - Impaired peripheral endothelial function in severe idiopathic pulmonary
      hypertension correlates with the pulmonary vascular response to inhaled iloprost.
AB  - BACKGROUND: Pulmonary endothelial function is known to be impaired in subjects
      with idiopathic pulmonary arterial hypertension (IPAH), but peripheral
      endothelial dysfunction and its predictive value for pulmonary vasoreactivity
      have not been previously investigated. METHODS: Measurements of peripheral
      endothelium-dependent and endothelium-independent vasoreactivity using flow
      mediated dilation (FMD) and nitroglycerin-mediated dilation of the brachial
      artery were performed in 18 patients with severe IPAH (15 women; mean age 50
      years [95% confidence interval 46-55 years], mean pulmonary artery pressure [PAP]
      51 mm Hg [43-59 mm Hg], pulmonary vascular resistance [PVR] 1239 dyn s cm(-5)
      [861-1618 dyn s cm(-5)] at baseline) and in 36 age- and sex-matched controls. In
      patients with IPAH, acute pulmonary vasoreactivity was measured as pulmonary
      vascular response to inhaled iloprost (PVRII) during pulmonary catheterization.
      RESULTS: Compared to controls, patients with IPAH demonstrated impaired
      peripheral endothelial function (FMD, 0.19 [0.07-0.31] vs 0.38 [0.30-0.44] mm
      among controls; P =.002). No such impairment was observed for nitroglycerin
      mediated dilation (0.34 [0.23-0.46] vs 0.36 [0.20-0.51] mm among controls; P =
      .679). Among patients with IPAH, iloprost lowered mean PAP by 8.2 mm Hg (2.0-14.5
      mm Hg) (P = .001) and PVR by 395 dyn s cm(-5) (109-680 dyn s cm(-5)) (P < .001).
      Subsequent analysis of the association between peripheral endothelial function
      and PVRII disclosed a correlation of FMD with the percent decrease in mean PAP (r
      = .65, P = .003) and PVR (r = 0.67, P = .002), in which patients with IPAH with
      the greatest PVRII also exhibited the highest FMD values. CONCLUSIONS: Idiopathic
      pulmonary arterial hypertension is associated with peripheral endothelial
      dysfunction. Peripheral endothelium-dependent vasoreactivity correlates with the
      PVRII. It remains to be established if FMD has the potential as a clinical tool
      for noninvasive estimation of pulmonary vasoreactivity in IPAH.

PMID- 17540216
TI  - Where patients with mild to moderate heart failure die: results from the Sudden
      Cardiac Death in Heart Failure Trial (SCD-HeFT).
AB  - BACKGROUND: Common locations of death in patients with congestive heart failure
      (CHF) are unknown. In the SCD-HeFT, mortality of patients with CHF was assessed
      after randomization to an implantable cardioverter/defibrillator (ICD),
      amiodarone, or placebo. The aim of this study was to evaluate the location of
      deaths in SCD-HeFT. METHODS: Among SCD-HeFT patients whose location of death was
      identified, we used logistic regression to assess the relationship of randomized
      treatment arm and other baseline predictors with the location of death. Cause of
      death was adjudicated by a therapy-blinded events committee. RESULTS: In SCD
      HeFT, 666 (26%) of 2521 patients died. Of the 604 (91%) for whom location of
      death was known, 58% died in hospital and 29% died at home. Patients randomized
      to receive an ICD were less likely to die at home than patients randomized to
      placebo (P = .002). Fewer patients randomized to ICDs died; even fewer randomized
      to ICDs died at home. Age, sex, etiology of heart failure, left ventricular
      ejection fraction, and New York Heart Association functional class were not
      associated with location of death. Sudden cardiac death represented 52% of all
      out-of-hospital deaths but in hospital deaths exceeded out-of-hospital deaths.
      CONCLUSION: Deaths in SCD-HeFT, a well-treated CHF population, were most often in
      hospital. ICDs were associated with lower total and sudden death rates at home
      and in hospital. Development of methods to identify which patients will not
      respond to optimal treatment, including an ICD, remain a challenge.

PMID- 17540217
TI  - Type-D personality, depression, and cardiac prognosis: cortisol dysregulation as
      a mediating mechanism.

PMID- 17540218
TI  - Changes in mood predict disease activity and quality of life in patients with
      psoriasis following emotional disclosure.
AB  - OBJECTIVE: The present study examined the effects of emotional disclosure (ED)
      intervention on both disease severity and quality of life in patients with
      psoriasis. METHODS: Fifty-nine patients were recruited (mean age, 50 years; 32
      men and 27 women; mean length of diagnosis, 22 years). Individuals were randomly
      assigned to receive ED intervention or standard control writing intervention.
      Disease severity, quality of life, and mood were assessed at baseline and at 2,
      8, and 12 weeks postintervention. RESULTS: Disease severity and quality of life
      improved in both groups over the follow-up period. Preliminary analysis suggested
      no differences in the magnitude of improvement between the groups. However,
      predictors of improvement were found to differ. Disease severity on Week 12 was
      predicted by changes in mood in intervention patients and seasonal variation in
      control patients. In contrast, quality of life on Week 12 was predicted by
      baseline quality of life in intervention patients, while seasonal variation
      approached significance for control patients. CONCLUSIONS: Changes in mood
      following ED predicted improvements in disease severity in patients with
      psoriasis. However, the degree of improvement did not differ between intervention
      and control patients.

PMID- 17540219
TI  - The process of symptom appraisal: cognitive and emotional responses to detecting
      potentially malignant oral symptoms.
AB  - OBJECTIVE: Following the self-discovery of symptoms of oral cancer, approximately
      30% of patients wait for more than 3 months before seeking attention from a
      health care professional. Although symptom appraisal is known to be an important
      stage in the decision to seek help, little is known about the process of symptom
      appraisal. The aims of the current study were to produce a theory-guided
      investigation of the specific cognitive interpretations and emotional reactions
      to the self-discovery of potentially malignant oral symptoms and to gain
      understanding as to why these may change prior to help seeking. METHODS: In-depth
      semi-structured interviews were conducted with 57 consecutive patients who had
      been referred with potentially malignant oral symptoms. Participants were asked
      about symptom detection, initial and subsequent beliefs about symptoms, and
      emotional responses prior to their first visit to a health care professional. The
      tape-recorded interviews were transcribed verbatim and analyzed using "framework
      analysis." RESULTS: Patients often attributed the symptoms to transient, minor
      conditions such as mouth ulcers, physical trauma, or dental problems and, in turn
      were unconcerned about their presence. Patients infrequently attributed their
      symptoms to cancer. Origins of specific interpretations included previous
      experiences, specific symptomatology, logical associations with the perceived
      cause, and information from medical literature. Stimuli for reinterpretation
      included receipt of new information, symptom development, and persistence of
      symptoms. CONCLUSION: This study has documented the process of symptom appraisal
      and indicates that an individual's interpretation of potentially malignant oral
      symptoms is often misguided.

PMID- 17540220
TI  - Emotional reactions following exposure to idealized bodies predict unhealthy body
      change attitudes and behaviors in women and men.
AB  - OBJECTIVE: We explored the extent to which changes in emotional states following
      exposure to images of idealized bodies predict unhealthy body change attitudes
      and behaviors in women and men, and whether particular psychological traits
      mediate these effects. METHOD: One hundred thirty-three women and 93 men were
      assessed for unhealthy attitudes and behaviors related to body weight and muscles
      using the Eating Disorder Inventory-2 (EDI-2), the Obligatory Exercise
      Questionnaire, and the strategies to increase muscles subscale of the Body Change
      Inventory. Psychological traits assessed included body dissatisfaction (EDI-2),
      internalization of the thin/athletic ideal (Sociocultural Attitudes Towards
      Appearance Questionnaire-3), body comparison (Body Comparison Scale), self-esteem
      (Rosenberg Self-Esteem Inventory), depression (Beck Depression Inventory-II), and
      identity confusion (Self-Concept Clarity Scale). Participants were then exposed
      to photographs of thin female models and muscular male models, and visual
      analogue scales were used to measure changes in postexposure state body
      dissatisfaction, anger, anxiety, and depression. RESULTS: Postexposure increases
      in state anger, anxiety, depression, and body dissatisfaction correlated with
      drive for thinness and disordered eating symptomatology in women, while
      postexposure increases in state body dissatisfaction correlated with muscle
      development in men. Analyses revealed that internalization and body comparison
      mediated these relationships, with trait body dissatisfaction, trait depression,
      self-esteem, and self-concept/identity confusion serving as mediators for women
      only. CONCLUSION: These results are indicative of gender differences in: (a)
      reactions to idealized bodies; (b) psychological traits that predispose
      individuals to experience these reactions; and (c) types of body change behavior
      that are associated with these reactions.

PMID- 17540221
TI  - An evaluation of the absolute and relative stability of alexithymia in women with
      breast cancer.
AB  - OBJECTIVES: In the controversy for alexithymia as a state or a trait dimension,
      recent studies showed that, whereas absolute changes (i.e., extent of alexithymia
      scores change over time) were observed, alexithymia was relatively stable (i.e.,
      extent to which relative differences among individuals remain the same over
      time). The present study extended this question by investigating a disease with
      highly threatening outcomes (breast cancer), by looking at changes in depression
      and anxiety, and by examining stability for total and factor alexithymia scores.
      METHODS: One hundred twenty-two women in treatment for a first instance of breast
      cancer were assessed for alexithymia (TAS-20), depression, and anxiety (HADS) the
      day before surgery (T1) and six months later (T2). RESULTS: Alexithymia scores
      changed from baseline to follow-up (lack of absolute stability). Strong evidence
      of relative stability was also demonstrated, as alexithymia scores at baseline
      correlated significantly with alexithymia scores at follow-up and were also a
      significant predictor of follow-up alexithymia scores, after partialling the
      effects of depression and anxiety severity. Changes in alexithymia were explained
      only to a small extent by changes in depression and anxiety from T1 to T2.
      Results at the factor level revealed that "difficulty identifying feelings"
      follow-up and change score accounted for the highest variations in depression and
      anxiety, and "externally oriented thinking" for the lowest ones. CONCLUSIONS: The
      finding of relative stability of alexithymia supports the view that this
      construct is a stable personality trait rather than a state-dependent phenomenon,
      even in a context of high threat for physical and psychological integrity.

PMID- 17540222
TI  - Regulation of emotions during experimental stress in alexithymia.
AB  - OBJECTIVE: The aim of this study was to examine whether deficits in emotion
      regulation manifest as a relative lack of congruence between subjective reports
      of emotion and autonomic activity when confronted with stressors. METHODS: A pool
      of 830 university students was screened using the Toronto Alexithymia Scale
      Revised for deficits in emotion regulation associated with alexithymia. Those
      meeting a criterion floor cutoff and other inclusion criteria composed the
      experimental group and were matched on age, gender, and race to those in the
      control group. A final sample size of 94 students (47 in each group) was
      presented with experimental stressor tasks (the Stroop task and a conversation
      task) in counterbalanced order while autonomic activity data (heart rate and skin
      conductance) and subjective reports of negative affect were continuously
      collected during baseline, stressor exposure, and recovery periods. Data were
      analyzed to determine relative differences in congruence between the autonomic
      and subjective measures. RESULTS: Data suggested that participants high in
      emotion regulation deficits reported consistently higher subjective negative
      affect relative to those without such deficits throughout baseline, stressor
      exposure, and recovery periods. However, autonomic activity remained nearly
      identical in both groups across phases. Explicit tests of group differences in
      congruence between autonomic and subjective emotion measures also partly
      supported evidence of subjective hyperarousal. CONCLUSIONS: Deficits in emotion
      regulation, as evidenced in those with high levels of the alexithymic trait,
      appear to manifest as chronically elevated subjective negative affect relative to
      autonomic activity regardless of the level of environmental demands. Theoretical
      and clinical implications of these findings are discussed.

PMID- 17540223
TI  - Alexithymia and occupational burnout are strongly associated in working
      population.
AB  - OBJECTIVE: The relationship between alexithymia and occupational burnout has not
      previously been studied. We investigated the association between alexithymia and
      occupational burnout in a representative nationwide population health study.
      METHODS: This study was a part of the Finnish Health 2000 Study. The nationally
      representative sample comprised 3322 employees aged 30-64 years. Alexithymia was
      measured with the 20-item Toronto Alexithymia Scale (TAS-20) and occupational
      burnout with the Maslach Burnout Inventory-General Survey. Sociodemographic and
      health-related variables including depression were treated as confounders in the
      logistic regression analyses, which were performed alternately with TAS-20 total
      score and the scores of the three TAS-20 factor scales as alexithymia variables.
      RESULTS: Alexithymia and its three facets were significantly associated with
      occupational burnout even when controlled for confounding factors. CONCLUSIONS:
      Even though both alexithymia and depression are associated with burnout,
      alexithymia may be an independent risk factor for occupational burnout.

PMID- 17540225
TI  - Personality disorders in somatization disorder patients: a controlled study in
      Spain.
AB  - OBJECTIVE: The aim of this paper is to assess personality disorder (PD)
      comorbidity in somatization disorder (SD) patients compared with psychiatric
      controls in a Spanish sample. METHODS: This is a case-control study. Selection of
      70 consecutive SD patients was made, and an age-, sex-, and ethnic-group-matched
      control group of 70 mood and/or anxiety disorder patients recruited in
      psychiatric outpatient clinics was selected. PDs were measured using the
      International Personality Disorder Examination, and Diagnostic and Statistical
      Manual of Mental Disorders, Fourth Edition Axis I morbidity was measured by means
      of the Standardized Polyvalent Psychiatric Interview. RESULTS: PD comorbidity in
      SD patients was 62.9%, compared to 28.2% in controls [odds ratio (OR)=3.7; 95%
      confidence interval (95% CI)=1.8-7.6]. The highest ORs of PD in SD patients,
      compared with controls, were for paranoid (OR=9.2; 95% CI=1.9-43), obsessive
      compulsive (OR=6.2; 95% CI=1.2-53.6), and histrionic (OR=3.6; 95% CI=0.9-13.9)
      PDs. CONCLUSIONS: This is a controlled study with the largest sample of SD
      patients. The prevalence of PD comorbidity is similar to that of a previously
      published controlled study but is different from those of the most frequent PD
      subtypes.

PMID- 17540224
TI  - Alexithymia and 7.5-year incidence of compensated low back pain in 1207 urban
      public transit operators.
AB  - OBJECTIVE: Alexithymia, a lack of emotional awareness, was positively associated
      with self-reported low back pain (LBP) in cross-sectional studies. We assessed
      the association of alexithymia with 7.5-year incidence of LBP prospectively in a
      cohort study of 1207 San Francisco transit operators. METHODS: Alexithymia was
      measured by the 20-item Toronto Alexithymia Scale (TAS-20). LBP was assessed by
      physician-confirmed diagnoses from administrative workers' compensation data. Cox
      proportional hazards analyses controlled for demographic, behavioral, and
      physical and psychosocial job factors measured by questionnaire and interview.
      RESULTS: Of all drivers, 27.7% (n=334) filed compensated claims for LBP injuries
      with workers' compensation insurance during the 7.5-year observation time. The
      hazard ratios from the fully adjusted model were 0.73 (0.56-0.96) for the TAS-20
      scale and 0.82 (0.69-0.98) for the subscale "difficulty describing feelings."
      Alexithymia scores did not predict the duration of compensated work disability.
      CONCLUSION: In contrast to previous cross-sectional positive associations between
      alexithymia and LBP, alexithymia is negatively associated with compensated LBP
      claims. We hypothesize that shame and reporting behavior may explain these
      inconsistent results.

PMID- 17540226
TI  - Prevalence of eating disorders among adolescent and young adult scholastic
      population in the region of Madrid (Spain).
AB  - OBJECTIVE: The prevalence of eating disorders (EDs) in a representative
      scholastic sample was evaluated, and the demographic factors associated with ED
      were assessed. METHOD: The study used a two-stage epidemiological design. The
      study population was a randomly selected sample of 1545 students (12- to 21-year
      old males and females) in the region of Madrid (Spain). RESULTS: ED prevalence
      was 3.43%. Prevalence estimations were as follows: 5.34% for females: 2.72% for
      eating disorders not otherwise specified (EDNOS), 2.29% for bulimia nervosa (BN),
      and 0.33% for anorexia nervosa (AN); and 0.64% for males: 0.48% for EDNOS, 0.16%
      for BN, and 0.00% for AN. Some demographic factors that were shown to be
      associated with ED included the following: sex, age, single child, single-parent
      families, and father or mother's death. DISCUSSION: Despite the methodological
      improvements over previous epidemiological studies developed in Spain, there were
      no significant differences in the prevalence estimations.

PMID- 17540227
TI  - Long-term weight loss maintenance after inpatient psychotherapy of severely obese
      patients based on a randomized study: predictors and maintaining factors of
      health behavior.
AB  - OBJECTIVE: The objective of this study was to identify predictors of long-term
      weight loss after inpatient psychodynamic or behavioral psychotherapy of severely
      obese patients. METHODS: In a longitudinal study, obese patients [body mass index
      (BMI)>or=35 kg/m(2)] were randomly assigned to behavioral or psychodynamic
      inpatient treatment. The average treatment duration was 7 weeks. Two hundred
      sixty-seven obese patients, mostly female (85%), with psychiatric and somatic
      comorbidity (age, 20-64 years; BMI=35-74 kg/m(2)) were examined with standardized
      self-report scales at intake, discharge, 1-year follow-up, and 3-year follow-up.
      RESULTS: Overall, 3 years after inpatient psychotherapy, irrespective of
      treatment setting, we found an average weight loss of about 1 BMI unit (2% or 3
      kg). Effect size for weight loss was small (ES=0.26); changes in body image were
      stronger (ES=0.56). About 32% of patients achieved a long-term weight loss of
      >5%. In multiple regressions, weight loss was predicted by the attribution of
      overweight to eating habits, low dominance (Inventory of Interpersonal Problems),
      low life satisfaction, higher initial weight loss, and higher self-efficacy.
      Weight loss maintenance was predicted by cognitive control and current physical
      activity on follow-up. CONCLUSION: In the long run, one third of patients could
      maintain or improve weight loss by inpatient psychotherapy. Lasting beneficial
      changes in body image and distress could also be found. The predictors of weight
      loss and weight loss maintenance identified in this study may be helpful for
      future modifications of psychotherapeutic intervention strategies.

PMID- 17540228
TI  - Laughter elevates the levels of breast-milk melatonin.
AB  - OBJECTIVE: Patients with atopic eczema (AE) often complain of sleep disturbance.
      Melatonin is involved in sleep, and the levels of blood melatonin in patients
      with AE are decreased in comparison to healthy subjects. However, the levels of
      breast-milk melatonin had only been reported in healthy subjects. Laughter
      increased natural killer cell activity in blood and free radical-scavenging
      capacity in saliva in healthy subjects. Thus, the effect of laughter on the
      levels of breast-milk melatonin was studied in mothers with AE. Moreover, the
      effect of feeding with breast milk after laughter on allergic responses in
      infants was studied. METHODS: Forty-eight infants aged 5-6 months were enrolled.
      All of the infants had AE and were allergic to latex and house dust mite (HDM).
      Half (n=24) of the mothers of these infants were patients with AE, while another
      24 mothers were healthy subjects. The mothers viewed either an 87-min humorous
      DVD (Modern Times, featuring Charlie Chaplin) or an 87-min nonhumorous weather
      information DVD at 2000 h. After viewing, breast milk was collected sequentially
      from 2200, 2400, 0200, 0400 to 0600 h. The levels of breast-milk melatonin were
      measured. In addition, skin wheal responses to HDM and histamine were studied in
      infants. RESULTS: Laughter caused by viewing a humorous DVD increased the levels
      of breast-milk melatonin in both mothers with AE and healthy mothers. In
      addition, allergic responses to latex and HDM of infants were reduced by feeding
      with breast milk after laughter of mothers with AE or of healthy mothers.
      CONCLUSION: Laughter increased the levels of breast-milk melatonin in both
      mothers with AE and healthy mothers, and feeding infants with increased levels of
      melatonin-containing milk reduced allergic responses in infants. Thus, laughter
      of mothers may be helpful in the treatment of infants with AE.

PMID- 17540229
TI  - Laughter modulates prorenin receptor gene expression in patients with type 2
      diabetes.
AB  - OBJECTIVE: The purpose of this study was to assess whether laughter influences
      the expression of the receptor gene for prorenin that participates in the
      progression of diabetic nephropathy. METHODS: Sixteen normal subjects and 23
      patients with type 2 diabetes [12 nephropathy (-) and 11 nephropathy (+)] were
      recruited to examine the effects of laughter on the modulation of prorenin
      receptor gene expression. After watching a comedy show, laughter-induced changes
      in the levels of blood prorenin and the expression of prorenin receptor gene were
      analyzed by an antibody-activating direct enzyme kinetic assay and by reverse
      transcriptase polymerase chain reaction, respectively. RESULTS: In diabetic
      patients, laughter decreased the level of blood prorenin [93.4-60.4 ng/l in
      nephropathy (-) patients, 196.6-166.7 ng/l in nephropathy (+) patients] and up
      regulated the prorenin receptor gene [1.49-fold in nephropathy (-) patients, 1.46
      fold in nephropathy (+) patients]. No significant changes in the expression of
      this gene were recognized in normal subjects. CONCLUSION: The beneficial effects
      of laughter on preventing the exacerbation of diabetic nephropathy are strongly
      suggested in terms of normalizing the expression of the prorenin receptor gene
      followed by reducing the level of blood prorenin.

PMID- 17540230
TI  - Factor analysis of the Massachusetts General Hospital Hairpulling Scale.
AB  - OBJECTIVE: We explored the factor structure of the Massachusetts General Hospital
      Hairpulling Scale (MGH-HPS), a self-report measure for trichotillomania (TTM).
      METHODS: Self-reported hairpullers who responded to an Internet-based survey
      (N=990) completed the MGH-HPS, demographic items, and other survey instruments.
      Principal axis exploratory factor analysis with Promax rotation of scores was
      conducted. RESULTS: A two-factor solution was revealed, with "Severity" and
      "Resistance and Control" as separate factors. CONCLUSION: The MGH-HPS consists of
      two separate factors. Factor scores can be utilized to track naturalistic TTM
      symptom changes, improve patient characterization and treatment matching, and
      clarify the timing and mechanism of action for different treatment modalities.

PMID- 17540232
TI  - The Lowbury Lecture. The United States approach to strategies in the battle
      against healthcare-associated infections, 2006: transitioning from benchmarking
      to zero tolerance and clinician accountability.
AB  - Approximately 2,000,000 healthcare-associated infections (HAIs) annually occur in
      US healthcare facilities and lead to approximately 60,000 90,000 deaths and cost
      $17 29 billion dollars. Such HAIs are an equal, if not more common problem,
      worldwide. Many evidence-based HAI prevention guidelines exist. However, despite
      knowing what to do, the challenge remains of getting clinicians to comply with
      these recommendations. In the USA, a variety of forces, including the public and
      legislators, are demanding HAI prevention. This is illustrated by the Consumers
      Union's effort to get legislation in every state for public HAI rate reporting.
      In addition, a number of profit-making and non-profit-making organizations have
      initiated major HAI prevention interventions. At least three common themes for
      these interventions exist. First, no single intervention prevents any HAI; rather
      a "bundle" approach, using a package of multiple interventions based on evidence
      provided by the infection control community and implemented by a
      multidisciplinary team is the model for successful HAI prevention. Second,
      benchmarking is inadequate and a culture of zero tolerance is required. Third, a
      culture of accountability and administrative support is required. Such
      interventions have illustrated that much greater levels of HAI prevention can be
      accomplished than ever estimated in the past. Implementation of evidence-based
      HAI prevention interventions should be a high priority for all healthcare
      facilities to reduce preventable HAIs to the greatest extent possible.

PMID- 17540233
TI  - Avian influenza and the threat of the next human pandemic.

PMID- 17540234
TI  - Halting the spread of human prion disease--exceptional measures for an
      exceptional problem.

PMID- 17540235
TI  - Potential bio-terror agents.

PMID- 17540236
TI  - Confronting infection in the English National Health Service.

PMID- 17540237
TI  - An overview of the UK Department of Health's Rapid Review Panel.

PMID- 17540238
TI  - Prevention of central venous catheter-related infections: what works other than
      impregnated or coated catheters?
AB  - Catheter-related bloodstream infections (CRBSI) are a significant cause of
      morbidity and excess hospital cost. Data from prospective, randomized trials
      demonstrate that the risk of these infections can be minimized by simple
      interventions. Changing the behaviour of healthcare workers who insert and care
      for intravascular catheters is imperative. Creating a culture of patient safety
      and assuring easy access to the products necessary to maintain strict asepsis
      during catheter insertion, dressing changes, and when manipulating catheter hubs,
      will enhance adherence to optimal practice and will reduce the risk posed to the
      millions of patients in need of such devices.

PMID- 17540239
TI  - An update on antimicrobial central venous catheters.
AB  - Antimicrobial central venous catheters make use of a variety of antimicrobial
      mechanisms. Although they are currently infrequently used and their role in
      preventing infection is still being defined, they have a clear application in
      certain situations.

PMID- 17540240
TI  - Prevention of infection in neurosurgery: role of "antimicrobial" catheters.

PMID- 17540241
TI  - Hospital and community acquired infection and the built environment--design and
      testing of infection control rooms.
AB  - Negative-pressure isolation rooms are required to house patients infected with
      agents transmissible by the aerosol route in order to minimise exposure of
      healthcare workers and other patients. Housing patients in a separate room
      provides a barrier which minimises any physical contact with other patients. An
      isolation room held at negative pressure to reduce aerosol escape and a high air
      change rate to allow rapid removal of aerosols can eliminate transmission of
      infectious aerosols to those outside the room. However, badly designed and/or
      incorrectly operating isolation rooms have been shown to place healthcare workers
      and other patients at risk from airborne diseases such as tuberculosis. Few
      standards are available for the design of isolation rooms and no pressure
      differential or air-change rates are specified. Techniques such as aerosol
      particle tracer sampling and computational fluid dynamics can be applied to study
      the performance of negative-pressure rooms and to assess how design variables can
      affect their performance. This should allow cost-effective designs for isolation
      rooms to be developed. Healthcare staff should be trained to understand how these
      rooms operate and there should be systems in place to ensure they are functioning
      correctly.

PMID- 17540242
TI  - Environmental contamination makes an important contribution to hospital
      infection.
AB  - Meticillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant
      enterococci (VRE) are capable of surviving for days to weeks on environmental
      surfaces in healthcare facilities. Environmental surfaces frequently touched by
      healthcare workers are commonly contaminated in the rooms of patients colonized
      or infected with MRSA or VRE. A number of studies have documented that healthcare
      workers may contaminate their hands or gloves by touching contaminated
      environmental surfaces, and that hands or gloves become contaminated with numbers
      of organisms that are likely to result in transmission to patients. Pathogens may
      also be transferred directly from contaminated surfaces to susceptible patients.
      There is an increasing body of evidence that cleaning or disinfection of the
      environment can reduce transmission of healthcare-associated pathogens. Because
      routine cleaning of equipment items and other high-touch surfaces does not always
      remove pathogens from contaminated surfaces, improved methods of disinfecting the
      hospital environment are needed. Preliminary studies suggest that hydrogen
      peroxide vapour technology deserves further evaluation as a method for
      decontamination of the environment in healthcare settings.

PMID- 17540243
TI  - Importance of environmental decontamination--a critical view.
AB  - The level of evidence supporting different disinfection and cleaning procedures
      performed in healthcare settings worldwide is low. With respect to environmental
      surfaces, the final assessment of whether use of disinfectants rather than
      detergents alone reduces nosocomial infection rates in different clinical
      settings still awaits conclusive study. It must be kept in mind that the effect
      of surface disinfection is only transient microbial contamination will have
      reached its former level within a few hours. While resistance to biocides is
      generally not judged to be as critical as antibiotic resistance, scientific data
      support the need for proper use, i.e. avoidance of widespread application,
      especially in low concentrations and in consumer products. The decontamination
      ability of the substances used; prevention of resistance; and safety for
      patients, personnel and the environment; are the cornerstones that interact with
      each other. Future work should focus on this complex background. Targeted
      disinfection of environmental surfaces (those frequently touched) is an
      established component of infection control activities to prevent the spread of
      nosocomial (multi-resistant) pathogens, but of lesser importance than proper hand
      hygiene. However, since the use of disinfectants may pose a danger to staff,
      patients and the environment, prudent use combined with the application of proven
      safety precautions is important. Since emerging resistant pathogens will
      challenge healthcare facilities in future even more than today, well-designed
      studies addressing the role of disinfection in the healthcare-setting are needed.

PMID- 17540244
TI  - Decontamination of the environment.

PMID- 17540245
TI  - Bacterial resistance to biocides in the healthcare environment: should it be of
      genuine concern?
AB  - The emergence of bacterial resistance following exposure in healthcare facilities
      has been a recurrent topic of interest over the last 10 years. The overwhelming
      and increasing body of evidence from studies in vitro showed that bacteria have
      an immense capacity to respond to chemical stress brought upon by biocides.
      Empirically two major types of mechanisms have been described: intrinsic and
      acquired. However, the increasing documented response from bacteria exposed to
      biocide in conditions close to those found in practice suggests that intrinsic
      resistance does not adequately describe bacterial survival mechanisms, and that
      other terms such as biofilm resistance and environmental resistance would be
      therefore more appropriate. In addition, such terms are more relevant when
      describing in-situ conditions. The lack of evidence of bacterial resistance in
      practice and the inability to correlate emerging bacterial resistance from in
      vitro experiments with practical situations is a major drawback when attempting
      to ascertain whether emerging bacterial resistance in healthcare facilities is of
      genuine concern. Microbial resistance to high or in-use concentration of biocides
      has been described in practice, although it remains uncommon. The efficacy of
      biocides in eliminating bacterial contaminants within healthcare facilities has
      to be questioned with the widespread and increasing use of products containing
      low concentrations of biocide or possessing low bactericidal activity, as is the
      selection of less susceptible bacteria following such exposure.

PMID- 17540246
TI  - The role of microbiology and pharmacy departments in the stewardship of
      antibiotic prescribing in European hospitals.
AB  - This observational, cross-sectional study describes the role played by clinical
      microbiology and pharmacy departments in the stewardship of antibiotic
      prescribing in European hospitals. A total of 170 acute care hospitals from 32
      European countries returned a questionnaire on antibiotic policies and practices
      implemented in 2001. Data on antibiotic use, expressed as Defined Daily Doses per
      100 occupied bed-days (DDD/100 BD) were provided by 139 hospitals from 30
      countries. A total of 124 hospitals provided both datasets. 121 (71%) of Clinical
      Microbiology departments and 66 (41%) of Pharmacy departments provided out of
      hours clinical advice. 70 (41%) of microbiology/infectious disease specialists
      and 28 (16%) of pharmacists visited wards on a daily basis. The majority of
      laboratories provided monitoring of blood cultures more than once per day and
      summary data of antibiotic susceptibility testing (AST) for empiric prescribing
      (86% and 73% respectively). Most of the key laboratory and pharmacy-led
      initiatives examined did not vary significantly by geographical location.
      Hospitals from the North and West of Europe were more likely to examine blood
      cultures more than once daily compared with other regions (p < 0.01). Hospitals
      in the North were least likely routinely to report susceptibility results for
      restricted antibiotics compared to those in the South-East and Central/Eastern
      Europe (p < 0.01). Hospital wards in the North were more likely to hold
      antibiotic stocks (100%) compared with hospitals in the South-East which were
      least likely (39%) (p < 0.001). Conversely, hospital pharmacies in the North were
      least likely to dispense antibiotics on an individual patient basis (16%)
      compared with hospital pharmacies from Southern Europe (60%) (p = 0.01).
      Hospitals that routinely reported susceptibility results for restricted
      antibiotics had significantly lower median total antibiotic use in 2001 (p <
      0.01). Hospitals that provided prescribing advice outside normal working hours
      had significantly higher antibiotic use compared with institutions that did not
      provide this service (p = 0.01). A wide range of antibiotic stewardship measures
      was practised in the participating hospitals in 2001, although there remains
      great scope for expansion of those overseen by pharmacy departments. Most
      hospitals had active antibiotic stewardship programmes led by specialists in
      infection, although there is no evidence that these were associated with reduced
      antibiotic consumption. There was also no evidence that pharmacy services reduced
      the amount of antibiotics prescribed.

PMID- 17540247
TI  - Achieving prudence in the prescribing of antimicrobials--using clinical
      pharmacists in English acute hospitals.

PMID- 17540248
TI  - Introducing the ORION Statement, a CONSORT equivalent for infection control
      studies.

PMID- 17540249
TI  - Confronting models with data.
AB  - Until now, most of the mathematical modelling work on nosocomial infections has
      used simple models that have permitted qualitative, but not reliable quantitative
      predictions about the likely effect of different interventions. Increasingly,
      researchers would like to use models to provide reliable quantitative answers to
      both scientific and policy questions. This requires confronting models with data.
      Here, we discuss the importance of this confrontation with data with reference to
      previous modelling work, and outline the standard methods for doing this. We then
      describe a powerful new set of tools that promises to allow us to provide better
      answers to such questions, making far greater use than current methods of the
      information content of highly detailed hospital infection datasets. These tools
      should allow us to address questions that would have been impossible to answer
      using previous analytical techniques.

PMID- 17540250
TI  - Meticillin-resistant Staphylococcus aureus (MRSA) in hospitals and the community:
      model predictions based on the UK situation.
AB  - Theoretical modelling has shown that patient movements in and out of hospitals
      are likely to affect nosocomial transmission dynamics considerably. The community
      acts as a "reservoir" and readmission of individuals colonised during previous
      admissions can result in sporadic transmission episodes within hospitals. We
      investigated patient movement patterns and frequency of readmissions using seven
      years of complete data from the University Hospitals of Leicester NHS Trust.
      Sufficient information is held on individual patients to study the heterogeneity
      in readmission. Overall, we found that an infected person has a 44.2% chance of
      being readmitted to the Trust while still infected. This value is far higher than
      previous estimates (3.7% [Cooper et al., Health Technol Assess 2003;7(39)]),
      highlighting the potential importance of transmission driven by hospital
      admissions. For this reason we believe consideration of readmissions from the
      community population to be critical to the success of hospital acquired infection
      control.

PMID- 17540251
TI  - Control of meticillin-resistant Staphylococcus aureus (MRSA) and the value of
      rapid tests.
AB  - The cornerstones of infection control are the identification of patients who are
      contagious for others, and taking appropriate control measures. Microbiological
      detection of pathogens can take from several minutes or hours (microscopy) up to
      several days (culture-dependent detection). Currently, meticillin-resistant
      Staphylococcus aureus (MRSA) is one of the most important pathogens in nosocomial
      infection control, and detection using culture will take 1 5 days. This delay in
      the result of culture leads to a suboptimal control strategy. In low endemic
      settings like The Netherlands, patients who are considered at increased risk of
      MRSA carriage are treated in isolation until the results of culture have
      confirmed the absence of MRSA. On average this will take 4 to 5 days. As
      approximately 95% of these patients will not carry MRSA, this leads to a high
      number of unnecessary isolation days. This could be reduced by a rapid diagnostic
      test. In high endemic settings, admission screening and isolation until proven
      negative reduces the incidence of MRSA in high-risk units of the hospital. This
      has been predicted in a mathematical model and has been confirmed in intervention
      studies. Such a strategy can be implemented much more efficiently when a rapid
      diagnostic test is available. Recently, a real-time polymerase chain reaction
      test has become available that can detect MRSA directly from patient samples and
      takes less than 2 hours. The first results have been encouraging, although there
      are strains that are not detected. This test is not primarily intended to be used
      as a diagnostic device but rather as a screening tool for infection control. Many
      other screening tests are under development which may prove useful tools for the
      optimization of infection control in the near future.

PMID- 17540252
TI  - Virulence determinants in community and hospital meticillin-resistant
      Staphylococcus aureus.
AB  - Staphylococcus aureus produces many virulence factors, most of which act in a
      synergistic and coordinated fashion. Some appear to be specifically associated
      with certain severe infections and are produced by meticillin-resistant
      Staphylococcus aureus (MRSA) clones distributed worldwide. Superantigenic
      exotoxins appear to be major virulence factors in hospital MRSA clones (HA-MRSA),
      and staphylococcal enterotoxin A (SEA) may be involved in the physiopathology of
      septic shock. Panton Valentine Leucocidin (PVL) has emerged as a major virulence
      factor in community-acquired Staphylococcus aureus (CA-MRSA) infections. In
      particular, the leukotoxic action of PVL is responsible for the high mortality
      rate associated with necrotizing pneumonia. CA-MRSA can also harbour the toxic
      shock toxin 1 (TSST-1) and rarely the exfoliative toxin.

PMID- 17540253
TI  - Defining common infections in children and neonates.

PMID- 17540254
TI  - The First Global Patient Safety Challenge "Clean Care is Safer Care": from launch
      to current progress and achievements.
AB  - Healthcare-associated infection is a major safety issue affecting the quality of
      care of hundreds of millions of patients every year in both developed and
      developing countries. To meet the goal of ensuring patient safety across
      healthcare settings around the globe, the World Health Organization launched the
      World Alliance for Patient Safety in October 2004. Healthcare-associated
      infections were identified as a fundamental work priority and selected as the
      topic of the First Global Patient Safety Challenge launched by the Alliance.
      Under the banner "Clean Care is Safer Care", the Challenge aims at implementing
      several actions to reduce healthcare-associated infections worldwide, regardless
      of the level of development of healthcare systems and the availability of
      resources. Implementation strategies include the integration of multiple
      interventions in the areas of blood safety, injection safety, clinical procedure
      safety, and water, sanitation and waste management, with the promotion of hand
      hygiene in healthcare as the cornerstone. Several initiatives have been
      undertaken to raise global awareness and to obtain country commitment to support
      action on this issue. The new Guidelines on Hand Hygiene in Health Care,
      including the most consistent scientific evidence available, have been issued in
      an advanced draft form. An implementation strategy is proposed therein to provide
      solutions to overcome obstacles to improvement in compliance with hand hygiene
      practices, together with a range of practical tools for use in healthcare
      settings. The latter are currently undergoing testing in several pilot sites to
      evaluate feasibility, acceptability and sustainability.

PMID- 17540255
TI  - Putting educational theory into clinical practice.

PMID- 17540256
TI  - Infection control education: how to make an impact--tools for the job.
AB  - Infection control education is difficult and time consuming, but there is
      persuasive evidence to demonstrate its effectiveness. When Infection Control
      practitioners are educating and influencing healthcare workers, compliance with
      the well-established guidance on implementation of health service research is
      advisable, and thus educative efforts must be repeated and administered as part
      of a concerted and multifaceted approach. Infection Control education must be
      specifically designed for and targeted at the groups of staff concerned, and
      medical staff pose especial problems. Recruitment of clinical champions from peer
      groups, and direct approaches from medical members of the Infection Control team
      are usually needed. Familiarity with only a limited range of published evidence
      is needed to answer the majority of clinicians who challenge Infection Control
      practices, and referral to higher medical and managerial authority is required
      very infrequently and as a last resort. Some recent initiatives in the NHS in
      England may make Infection Control education more difficult, and these are
      reviewed. New sanctions have been made available to hospitals and Infection
      control teams in the UK with the passing of the Health Act in 2006, and the
      effects of these allied to educative interventions on benchmarks such as
      hospitals' MRSA bacteraemia rates will be observed with interest.

PMID- 17540257
TI  - Public health and healthcare-associated infections in the Netherlands.

PMID- 17540258
TI  - Hospital infection control in the Netherlands.
AB  - In this paper, the organization of infection control in Dutch hospitals will be
      described generally. Local organization of infection control departments can of
      course differ due to special needs, special expertise or interests of the members
      of a department.

PMID- 17540259
TI  - Supporting evidence-based infection prevention and control practice in the
      National Health Service in England. The NHS/TVU/Intuition Approach.
AB  - All successful strategies for preventing healthcare-associated infections require
      a multifaceted evidence-based approach that includes providing practitioners with
      the best evidence for clinically effective practice and then supporting them to
      understand and use this evidence to minimise infection risks and increase patient
      safety. This paper describes how national evidence-based guidelines from the
      Department of Health and the National Institute for Health and Clinical
      Excellence in England form the foundations for ensuring the availability of best
      evidence to practitioners, and how the development of an associated e
      learning/blended learning programme is now supporting all NHS staff to
      effectively use this evidence to protect patients from the risk of preventable
      infections during care.

PMID- 17540260
TI  - Infection control in countries with limited resources.

PMID- 17540261
TI  - Simple measures save lives: an approach to infection control in countries with
      limited resources.

PMID- 17540262
TI  - Quality of information: a European challenge.
AB  - Since the end of the 1970s, many countries have started to set up programmes to
      control healthcare-associated infections (HAIs) and to achieve a safe and
      sustainable development of their healthcare facilities that minimises the risk of
      infection. Surveillance is a usual component of any organised programme to
      address the problem either at national, regional or local level. So a
      considerable effort has been made by the national Public Health Authorities of EU
      Member States to foster and extend the surveillance of HAI via the production of
      increasingly standardised indicators. This information is used by Infection
      Control teams to implement preventive strategies, to evaluate the magnitude of
      the problem and to understand variations in the risks of HAI. At the same time,
      Public Health authorities and healthcare financing agencies in several countries
      have attempted to generalise the production of such indicators at an official
      level and use them as a global approach for hospital quality assessment,
      accreditation, continuous quality improvement and communication with patients and
      the general population.

PMID- 17540263
TI  - European perspective on surveillance.
AB  - International comparisons yield interesting insights regarding quality of care,
      beyond the field of healthcare-associated infection (HAI) prevention. Therefore,
      the exchange of experiences of national surveillance systems should be
      encouraged. However, the interpretation of differences of HAI rates should be
      made very carefully. Differences in healthcare systems, legal and cultural
      aspects, as well as differences in the methods of the surveillance systems, may
      have an enormous influence. One of the most crucial aspects of surveillance data
      is their validity, therefore it would be very helpful to combine the experience
      of all European validation studies performed in order to develop a protocol for a
      meaningful and cost-effective method for performing validation studies. Meanwhile
      some national surveillance systems have shown their effectiveness with reductions
      of 24 57% for surgical site infections (SSIs) and 20 29% for HAI in ICUs. Today,
      mandatory public reporting is probably the most demanding problem for the
      national HAI surveillance systems in Europe. The exchange of experience between
      the European surveillance networks in this respect in particular--remains a
      cornerstone and will motivate further activities in the individual countries.

PMID- 17540264
TI  - Hospitals in Europe Link for Infection Control through Surveillance (HELICS).
      Inter-country comparison of rates of surgical site infection--opportunities and
      limitations.
AB  - Many countries in Europe have created national systems for the surveillance of
      healthcare associated infections (HCAI). The Hospitals in Europe Link for
      Infection Control through Surveillance (HELICS) has provided a standardised
      approach to surveillance of HCAI and formed a 'network of networks' to enable
      data from hospitals contributing to national networks also to be submitted to the
      HELICS database. This paper describes the set of surgical site infection
      surveillance data collected in 2004. It includes 111,361 operations in six
      categories of surgical procedure from 14 countries. The analysis demonstrates
      that incidence density provides a better measure for comparison than cumulative
      incidence as it takes some account of difference in length of post-operative stay
      and post-discharge surveillance. Comparisons should also take account of
      differences in mix of procedures, variation in risk factors and sensitivity of
      case finding. This rich dataset provides a unique opportunity to explore
      variation in rates of SSI and improve understanding of factors that impact on
      inter-country comparisons.

PMID- 17540265
TI  - European surveillance of ICU-acquired infections (HELICS-ICU): methods and main
      results.

PMID- 17540266
TI  - Surveillance of hospital-acquired infections in Australia--One Nation, Many
      States.
AB  - Surveillance programmes for hospital-acquired infections differ amongst the
      Australian states. Victoria, New South Wales, Queensland and South Australia have
      recent substantial initiatives in development of statewide programmes. Whilst the
      definitions for surgical site infections (SSIs) and bloodstream infections (BSI)
      developed by the Australian Infection Control Association (AICA) do not differ
      from the US National Nosocomial Infection Surveillance (NNIS) programme
      definitions for SSI and intensive care unit (ICU) acquired central line
      associated BSI, only two states use NNIS risk adjustment methods in reporting
      infection rates. Differences exist in the surgical procedures under surveillance,
      ICU surveillance, hospital-wide BSI surveillance, staff health immunization
      surveillance, process measures such us surgical antibiotic prophylaxis and small
      hospital programmes. Only in the area of antibiotic use surveillance has national
      consensus been reached. In Victoria, NNIS risk adjustment had limited usefulness
      in predicting SSIs, especially after coronary artery bypass graft (CABG) surgery.
      Ventilator-associated pneumonia (VAP) surveillance had limited acceptance, and is
      not undertaken in other states. Regular reporting of surgical antibiotic
      prophylaxis data has been followed by improvement in choice of antibiotic in some
      procedures. The South Australian programme for the surveillance of multiresistant
      organisms (MROs) has documented substantial improvement in meticillin-resistant
      Staphylococcus aureus (MRSA) morbidity over time coincident with the introduction
      of hand hygiene programmes and other measures. In Queensland, statewide
      monitoring of needlestick injuries is established. In Victoria, the small
      hospital programme concentrated on process measures, and in Queensland with a
      standardized investigation pathways for "signal" events. Data quality presented
      substantial challenges in small Victorian hospitals. Whilst state-based
      programmes have facilitated communication between hospitals and their
      coordinating centre, Australia still lacks national coordination and a national
      database on hospital infections. The differing approaches of the states
      illustrate many of the fundamental questions facing hospital infection
      surveillance today.

PMID- 17540267
TI  - Mandatory public reporting in the USA: an example to follow?
AB  - Increasingly states in the USA are enacting laws mandating reporting and
      disclosure of hospital-acquired infections (HAIs). The rapid development of
      legislation has occurred in response to increased coverage of HAIs in the
      mainstream media coupled with active involvement of consumer advocacy
      organizations. The transformation of healthcare in the USA into a commodity has
      fostered a strong role for consumer advocacy to which state legislative bodies
      have shown willingness to respond.

PMID- 17540268
TI  - Public reporting in the UK of hospital infections.

PMID- 17540269
TI  - Can organisational change reduce hospital acquired infections?

PMID- 17540270
TI  - Diagnosis of suspicious breast lesions using an empirical mathematical model for
      dynamic contrast-enhanced MRI.
AB  - The purpose of this study was to test whether an empirical mathematical model
      (EMM) of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) can
      distinguish between benign and malignant breast lesions. A modified clinical
      protocol was used to improve the sampling of contrast medium uptake and washout.
      T(1)-weighted DCE magnetic resonance images were acquired at 1.5 T for 22
      patients before and after injection of Gd-DTPA. Contrast medium concentration as
      a function of time was calculated over a small region of interest containing the
      most rapidly enhancing pixels. Then the curves were fitted with the EMM, which
      accurately described contrast agent uptake and washout. Results demonstrate that
      benign lesions had uptake (P<2.0 x 10(-5)) and washout (P<.01) rates of contrast
      agent significantly slower than those of malignant lesions. In addition,
      secondary diagnostic parameters, such as time to peak of enhancement, enhancement
      slope at the peak and curvature at the peak of enhancement, were derived
      mathematically from the EMM and expressed in terms of primary parameters. These
      diagnostic parameters also effectively differentiated benign from malignant
      lesions (P<.03). Conventional analysis of contrast medium dynamics, using a
      subjective classification of contrast medium kinetics in lesions as "washout,"
      "plateau" or "persistent" (sensitivity=83%, specificity=50% and diagnostic
      accuracy=72%), was less effective than the EMM (sensitivity=100%, specificity=83%
      and diagnostic accuracy=94%) for the separation of benign and malignant lesions.
      In summary, the present research suggests that the EMM is a promising alternative
      method for evaluating DCE-MRI data with improved diagnostic accuracy.

PMID- 17540271
TI  - Pixel-by-pixel analysis of DCE MRI curve patterns and an illustration of its
      application to the imaging of the musculoskeletal system.
AB  - Dynamic contrast enhanced (DCE) MRI is a widespread method that has found broad
      application in the imaging of the musculoskeletal (MSK) system. A common way of
      analyzing DCE MRI images is to look at the shape of the time-intensity curve
      (TIC) in pixels selected after drawing an ROI in a highly enhanced area. Although
      often applied to a number of MSK affections, shape analysis has so far not led to
      a unanimous correlation between these TIC patterns and pathology. We hypothesize
      that this might be a result of the subjective ROI approach. To overcome the
      shortcomings of the ROI approach (sampling error and interuser variability, among
      others), we created a method for a fast and simple classification of DCE MRI
      where time-curve enhancement shapes are classified pixel by pixel according to
      their shape. The result of the analysis is rendered in multislice, 2D color-coded
      images. With this approach, we show not only that differences on a short distance
      range of the TIC patterns are significant and cannot be appreciated with a
      conventional ROI analysis but also that the information that shape maps and
      conventional standard DCE MRI parameter maps convey are substantially different.

PMID- 17540272
TI  - Partial volume effect compensation for improved reliability of quantitative blood
      brain barrier permeability.
AB  - INTRODUCTION: Blood-brain barrier (BBB) plays an important role in the
      pathophysiology of many central nervous system disorders. In the past, a number
      of laboratory techniques have been proposed to quantify permeability coefficient,
      k(i), an important index of barrier function. Recently, MRI has been used to
      estimate k(i) based on the unidirectional tracer kinetics model in one
      compartment as proposed by Patlak et al. and has been found to be in good
      agreement with the gold standard quantitative autoradiography technique. Rapid
      data acquisition, a prerequisite of this MRI-based technique, causes a compromise
      in spatial resolution resulting in partial volume (PV) averaging, an effect that
      is seldom explicitly compensated for in quantitative neuroimaging studies. This
      may have profound effect on the reliability of estimates obtained using
      quantitative methods. Existing PV compensation techniques that use complex
      statistical algorithms perform corrections on stationary images. In this proof-of
      principle study, the effect of PV averaging on BBB permeability coefficient has
      been evaluated using a simulation model, and a postprocessing technique that
      makes use of dynamic information has been proposed for PV compensation in order
      to improve the reliability of this quantitative method. MATERIALS AND METHODS: A
      computer simulation model is presented, which evaluates the effect of PV
      averaging on permeability coefficient estimates. Beginning with a known k(i), a
      PV compensation technique is proposed, which aims at correcting calculated k(i)
      to obtain the original estimate. The application of the PV compensation technique
      is demonstrated in a rat stroke brain model. Magnetic resonance imaging
      experiments were performed in Wistar rats (n=2) on a 4.7-T scanner. After
      acquiring localizer, T2-weighted and diffusion-weighted images, a rapid T1
      mapping protocol was implemented to acquire one pre-gadolinium
      diethylenetriaminepentaacetic acid baseline data set followed by a series of
      postinjection data sets. The data were postprocessed without and with application
      of PV compensation technique to obtain a k(i) estimate. RESULTS AND DISCUSSION:
      The issue of PV averaging as a result of limited spatial resolution is often not
      addressed in quantitative MRI studies. In this work, simulation experiments have
      provided useful insight into the PV effects on permeability coefficient estimate.
      The findings of the simulation experiments agree well with the results obtained
      from MR experiments. Results from the MR experiments suggest that it may be
      important to perform PV compensation in order to improve the reliability of
      permeability coefficient estimates. Future work involves classification of tissue
      component into gray and white matter and CSF to improve the accuracy of the
      compensation technique and to investigate repeatability of the technique in a
      larger group of animals.

PMID- 17540273
TI  - Magnetic resonance microscopic imaging based on high-order intermolecular
      multiple-quantum coherences.
AB  - Most imaging studies using intermolecular multiple-quantum coherences (iMQCs)
      have focused on the two-spin dipolar interactions--zero and double quantum
      coherences. Here, we report the results of various experimental studies to assess
      the feasibility of magnetic resonance microscopy with high-order iMQCs in model
      systems at 7 and 14 T. Experimental results demonstrated that the iMQC
      microscopic images with high coherence orders are readily observable at high
      field and have unique contrast depending on the sample microstructure and
      coherence order.

PMID- 17540274
TI  - Reproducibility of GABA measurements using 2D J-resolved magnetic resonance
      spectroscopy.
AB  - We determined the reproducibility of GABA (gamma-aminobutyric acid) measurements
      using 2D J-resolved magnetic resonance spectroscopy (MRS) on a clinical 1.5-T MR
      imaging scanner. Two-dimensional J-resolved spectra were acquired in vitro across
      five GABA concentrations using a volume head coil and a 5-in. surface coil.
      Additional spectra using a sixth GABA phantom with a very low concentration and
      from a healthy volunteer were recorded in the 5-in. surface coil only. In each
      case, the 3.01-ppm GABA resonance was quantified; for comparison, the peak
      integrals of choline (3.2 ppm) and creatine (3.03 ppm) were recorded. At a
      physiological concentration (1.2 mM), in vitro GABA measurement was significantly
      more reproducible in the surface coil than in the volume coil (P=.005), with
      coefficients of variation (CVs) being less than 16% with the surface coil and up
      to 68% with the volume head coil. At the smallest concentration of in vivo GABA
      reported using other spectroscopy techniques (0.8 mM) and detected only using the
      surface coil, the CV for GABA was 23% and was less than 10% for choline and
      creatine, which compare favorably with results from published studies. In vivo,
      the CV for GABA measurement was 26%, suggesting that 2D J-resolved MRS would be
      suitable for detecting physiological changes in GABA, similar to those reported
      using other methods.

PMID- 17540275
TI  - Equilibrium signal intensity mapping, an MRI method for fast mapping of
      longitudinal relaxation rates and for image enhancement.
AB  - INTRODUCTION: Inhomogeneity of magnetic fields, both B(0) and B(1), has been a
      major challenge in magnetic resonance imaging (MRI). Field inhomogeneity leads to
      image artifacts and unreliability of signal intensity (SI) measurements. This
      work proposes and shows the feasibility of generating equilibrium signal
      intensity (SI(Eq)) maps that can be utilized either to speed up relaxation-rate
      measurement or to enhance image quality and relaxation-rate-based weighting in
      various applications. METHODS: A 1.5-T MRI scanner was used. In canines (n=4),
      myocardial infarction was induced, and 48 h after the administration of 0.05 mmol
      kg(-1) Gd(ABE-DTTA), a contrast agent with slow tissue kinetics, in vivo R(1)
      mapping was carried out using an inversion recovery (IR)-prepared, fast gradient
      echo sequence with varying inversion times (TIs). To test the SI(Eq) mapping
      method without the confounding effects of motion and blood flow, we carried out
      ex vivo R(1) mapping after the administration of 0.2 mmol kg(-1) Gd(DTPA) using
      an IR-prepared, fast spin-echo sequence in another group of dogs (n=2). R(1,full)
      maps and SI(Eq) maps were generated from the data from both sequences by three
      parameter nonlinear curve fitting of the SI versus TI dependence. R(1,full) maps
      served as the reference standard. Raw IR images were then divided by the SI(Eq)
      maps, yielding corrected SI maps (COSIMs). Additionally, R(1) values were
      calculated from each single-TI image separately, using the SI(Eq) value and a one
      parameter curve-fitting procedure (R(1,single)). Voxelwise correlation analysis
      was carried out for the COSIMs and the R(1,single) maps, both versus the standard
      R(1,full) maps. Deviations of R(1,single) from R(1,full) were statistically
      evaluated. RESULTS: In vivo, COSIM versus R(1,full) showed significantly (P<.05)
      better correlation [correlation coefficient (CC)=0.95] than SI versus R(1,full)
      with a TI=700-800 ms, which is 200-300 ms longer than the tau(null) (500 ms) of
      viable myocardium. With such TIs, SI versus R(1,full) yielded CCs of 0.86-0.88.
      R(1,single) versus R(1,full) yielded a peak CC of 0.96 at TI=700-900 ms. Mean
      deviations of R(1,single) from R(1,full) were below 5% for TIs between 500 and
      1000 ms. Ex vivo, where tau(null) was 300 ms, the advantage of correction with
      SI(Eq) was not in the improvement of linear correlation but more in the reduction
      of scatter. Peak CCs for SI versus R(1,full) and COSIM versus R(1,full) at TI=500
      ms were 0.96 for both. The ex vivo CC for R(1,single) versus R(1,full) at TI=500
      ms was 0.98. Mean deviations of R(1,single) from R(1,full) were below 5% for TIs
      between 400 and 700 ms. CONCLUSIONS: Once the corresponding SI(Eq) map is
      obtained from a control stack, R(1) can be obtained accurately, using only a
      single IR image and without the need for a stack of TI-varied images. This
      approach could be applied in various dynamic MRI studies where short measurement
      time, once the dynamics has started, is of essence. When using this method with
      IR-prepared T(1)-weighted images, it is essential that the single TI be chosen
      such that the longitudinal relaxation in all voxels of interest would have passed
      tau(null). SI(Eq) maps are also useful in eliminating confounders from MR images
      to allow obtaining SI values that reflect more faithfully the relaxation
      parameter (R(1)) sought.

PMID- 17540276
TI  - Manganese-enhanced auditory tract-tracing MRI with cochlear injection.
AB  - Recent studies have demonstrated the use of manganese ion (Mn2+)) as an in vivo
      neuronal tract tracer. In contrast to histological approaches, manganese tracing
      can be performed repeatedly on the same living animal. In this study, we describe
      the neuroaxonal tracing of the auditory pathway in the living guinea pig, relying
      on the fact that Mn2+ ion enters excitable cells through voltage-gated calcium
      channels and is an excellent MRI paramagnetic tract-tracing agent. Small focal
      injections of Mn2+ ion into the cochlea produced significant contrast enhancement
      along the known neuronal circuitry. This in vivo approach, allowing repeated
      measures, is expected to open new vistas to study auditory physiology and to
      provide new insights on in vivo axonal transport and neuronal activity in the
      central auditory system.

PMID- 17540277
TI  - Longitudinal magnetic resonance imaging of spinal cord injury in mouse: changes
      in signal patterns associated with the inflammatory response.
AB  - Contusion-type spinal cord injury (SCI) in mice was followed longitudinally using
      in vivo magnetic resonance (MR) imaging along with neurobehavioral tests
      performed on postinjury Days 1, 7, 14 and 28. Magnetic resonance images were
      acquired from seven injured wild-type mice using a 9.4-T scanner and presented in
      sagittal and axial views to reflect the current state of the injured cord
      neuropathology on each day. The data were analyzed individually to gain more
      insights on the neuroinflammatory response unique to the mouse, to characterize
      the spatiotemporal evolution of the lesion and to quantify the changes in lesion
      volume and length with time. The MR intensity patterns on Day 1 showed acute
      injuries as focal in one group of three mice and as diffuse in the remaining
      group of four mice. The focal injuries appeared as a region of hypointensity with
      well-defined boundaries. These injuries first enlarged on Day 7, but then shrunk
      slightly by Days 14 and 28. In contrast, the diffuse injuries were initially
      obscure on Day 1, mainly because of loss of contrast between gray and white
      matters. On Day 7, lesions expanded asymptotically in both rostral and caudal
      directions with respect to the epicenter, and maintained its size on Days 14 and
      28. Previous studies based on postmortem histological analysis have reported
      lesions behaving more like in the focal group. However, this new injury with
      diffuse characteristics may have important implications for SCI research carried
      out with mice. Unique experiments on genetically engineered mice with altered
      neuroinflammatory response should help clarify the origin of these differences in
      the lesion formation.

PMID- 17540278
TI  - Single-shot fast spin-echo diffusion tensor imaging of the lumbar spine at 1.5
      and 3 T.
AB  - Diffusion tensor imaging (DTI) of the lumbar spine could improve diagnostic
      specificity. The purpose of this work was to determine the feasibility of and to
      validate DTI with single-shot fast spin-echo (SSFSE) for lumbar intervertebral
      discs at 1.5 and 3 T. Six normal volunteers were scanned with DTI-SSFSE using an
      eight- and a three-b-value protocol at 1.5 and 3 T, respectively. Apparent
      diffusion coefficient (ADC) values were computed and validated based on those
      obtained at 1.5 T from corresponding diffusion tensor scans using line scan
      diffusion imaging (LSDI), a technique that has been previously validated for use
      in the spine. Pearson correlation coefficients for LSDI and DTI-SSFSE ADC values
      were .88 and .89 for 1.5 and 3 T, respectively, with good quantitative agreement
      according to the Bland-Altman method. Results indicate that DTI-SSFSE is a
      candidate as a clinical sequence for obtaining diffusion tensor images of the
      lumbar intervertebral discs with scan times shorter than 4 min.

PMID- 17540279
TI  - Optimal coil array design: the two-coil case.
AB  - The optimization problem for coil arrays is largely unsolved, even for the case
      of a two-coil system. This paper reports a systematic computer simulation to
      investigate the maximal achievable signal-to-noise ratio (SNR) with a two-coil
      receiver system where, using cancellation circuitry, mutual inductance is made
      zero. Both symmetrical and asymmetrical solutions with respect to two-coil
      geometry are considered. SNR is measured at a single point at a certain depth and
      also along a longitudinal or transverse line at the same depth. The conducting
      medium containing these regions of interest is assumed to be an infinite half
      space, an infinite cylinder or a finite sphere. The previous coil array design
      using a "magical" overlap only approximates the optimal solution for the infinite
      half space. For the infinite cylinder and the finite sphere, optimal solutions
      can be quite different from the "magical" overlap.

PMID- 17540280
TI  - Parallel imaging for first-pass myocardial perfusion.
AB  - Two parallel imaging methods used for first-pass myocardial perfusion imaging
      were compared in terms of signal-to-noise ratio (SNR), contrast-to-noise ratio
      (CNR) and image artifacts. One used adaptive Time-adaptive SENSitivity Encoding
      (TSENSE) and the other used GeneRalized Autocalibrating Partially Parallel
      Acquisition (GRAPPA), which are both applied to a gradient-echo sequence. Both
      methods were tested on 12 patients with coronary artery disease. The order of
      perfusion sequences was inverted in every other patient. Image acquisition was
      started during the administration of a contrast bolus followed by a 20-ml saline
      flush (3 ml/s), and the next perfusion was started at least 15 min thereafter
      using an identical bolus. An acceleration rate of 2 was used in both methods, and
      acquisition was performed during breath-holding. Significantly higher SNR, CNR
      and image quality were obtained with GRAPPA images than with TSENSE images.
      GRAPPA, however, did not yield a higher CNR when applied after the second bolus.
      GRAPPA perfusion imaging produced larger differences between subjects than did
      TSENSE. Compared to TSENSE, GRAPPA produced significantly better CNR on the first
      bolus. More consistent SNR and CNR were obtained from TSENSE images than from
      GRAPPA images, indicating that the diagnostic value of TSENSE may be better.

PMID- 17540281
TI  - Performance of blind source separation algorithms for fMRI analysis using a group
      ICA method.
AB  - Independent component analysis (ICA) is a popular blind source separation
      technique that has proven to be promising for the analysis of functional magnetic
      resonance imaging (fMRI) data. A number of ICA approaches have been used for fMRI
      data analysis, and even more ICA algorithms exist; however, the impact of using
      different algorithms on the results is largely unexplored. In this paper, we
      study the performance of four major classes of algorithms for spatial ICA,
      namely, information maximization, maximization of non-Gaussianity, joint
      diagonalization of cross-cumulant matrices and second-order correlation-based
      methods, when they are applied to fMRI data from subjects performing a visuo
      motor task. We use a group ICA method to study variability among different ICA
      algorithms, and we propose several analysis techniques to evaluate their
      performance. We compare how different ICA algorithms estimate activations in
      expected neuronal areas. The results demonstrate that the ICA algorithms using
      higher-order statistical information prove to be quite consistent for fMRI data
      analysis. Infomax, FastICA and joint approximate diagonalization of eigenmatrices
      (JADE) all yield reliable results, with each having its strengths in specific
      areas. Eigenvalue decomposition (EVD), an algorithm using second-order
      statistics, does not perform reliably for fMRI data. Additionally, for iterative
      ICA algorithms, it is important to investigate the variability of estimates from
      different runs. We test the consistency of the iterative algorithms Infomax and
      FastICA by running the algorithm a number of times with different
      initializations, and we note that they yield consistent results over these
      multiple runs. Our results greatly improve our confidence in the consistency of
      ICA for fMRI data analysis.

PMID- 17540282
TI  - Evaluation of optimal density weighting for regridding.
AB  - Density weighting is a necessary component of the regridding algorithm for
      interpolating nonuniformly sampled data points onto a regular grid. Differing
      concepts of optimality for the density weighting have been proposed previously.
      The present study reviews some of these concepts and evaluates the accuracy of
      different techniques by comparison with the image obtained by a computationally
      intensive least squares minimization. A variant on one of the techniques is
      proposed that yields the highest accuracy of those studied.

PMID- 17540283
TI  - Methods for quantitative image quality evaluation of MRI parallel
      reconstructions: detection and perceptual difference model.
AB  - Many reconstruction algorithms are being proposed for parallel magnetic resonance
      imaging (MRI), which uses multiple coils and subsampled k-space data, and a
      quantitative method for comparison of algorithms is sorely needed. On such
      images, we compared three methods for quantitative image quality evaluation:
      human detection, computer detection model and a computer perceptual difference
      model (PDM). One-quarter sampling and three different reconstruction methods were
      investigated: a regularization method developed by Ying et al., a simplified
      regularization method and an iterative method proposed by Pruessmann et al.
      Images obtained from a full complement of k-space data were also included as
      reference images. Detection studies were performed using a simulated dark tumor
      added on MR images of fresh bovine liver. Human detection depended strongly on
      reconstruction methods used, with the two regularization methods achieving better
      performance than the iterative method. Images were also evaluated using detection
      by a channelized Hotelling observer model and by PDM scores. Both predicted the
      same trends as observed from human detection. We are encouraged that PDM gives
      trends similar to that for human detection studies. Its ease of use and
      applicability to a variety of MRI situations make it attractive for evaluating
      image quality in a variety of MR studies.

PMID- 17540284
TI  - An evaluation of reconstructed ACL impingement on PCL using MRI.
AB  - Using magnetic resonance imaging (MRI), we evaluated 42 reconstructed anterior
      cruciate ligaments (ACLs) for impingement on corresponding posterior cruciate
      ligaments (PCLs) in the knee-extended position. Thirty-one single-bundle ACL
      reconstructions and 11 double-bundle ACL reconstructions were performed. MR
      examinations were performed at 3 and 12 months after arthroscopic ACL
      reconstructions. Using oblique axial MRIs of reconstructed ACLs, we evaluated the
      shape of the PCL and divided them into two groups: an impingement-positive group
      and an impingement-negative group. Using sagittal images, we measured the PCL
      index (Liu's method) and examined the correlation between the degree of
      impingement and the index. At 3 months after surgery, 14 of 31 single-bundle ACL
      reconstructions and 5 of 11 double-bundle ACL reconstructions were regarded as
      positive impingement on PCLs. At 12 months after surgery, 17 of 31 single-bundle
      ACL reconstructions and 5 of 11 double-bundle ACL reconstructions were regarded
      as positive impingement on PCLs. At 3 months in single-bundle reconstructions and
      at 3 and 12 months in all reconstructions, the PCL index of the impingement
      positive group was significantly lower than that of the negative group. This
      study indicated that reconstructed ACLs in the impingement-positive group pressed
      the PCLs more posteriorly than did the impingement-negative group.

PMID- 17540285
TI  - Texture analysis of MR image for predicting the firmness of Huanghua pears (Pyrus
      pyrifolia Nakai, cv. Huanghua) during storage using an artificial neural network.
AB  - Firmness, a main index of quality changes, is important for the quality
      evaluation of fruits. In the present study, texture analysis (TA) of magnetic
      resonance images was applied to predict the firmness of Huanghua pears (Pyrus
      pyrifolia Nakai, cv. Huanghua) during storage using an artificial neural network
      (ANN). Seven co-occurrence matrix-derived TA parameters and one run-length matrix
      TA parameter significantly correlated with firmness were considered as inputs to
      the ANN. Several ANN models were evaluated when developing the optimal topology.
      The optimal ANN model consisted of one hidden layer with 17 neurons in the hidden
      layer. This model was able to predict the firmness of the pears with a mean
      absolute error (MAE) of 0.539 N and R=0.969. Our data showed the potential of TA
      parameters of MR images combined with ANN for investigating the internal quality
      characteristics of fruits during storage.

PMID- 17540286
TI  - Determination of blood longitudinal relaxation time (T1) at high magnetic field
      strengths.
AB  - In this study, a circulation system was used to measure T(1) values of bovine
      blood under physiological conditions at field strengths of 4.7, 7 and 9.4 T.
      Results show that T(1) increases linearly with magnetic field B(0) and can be
      described with the equation T(1)=129 ms/T B(0)+1167 ms for magnetic field
      strengths between 1.5 and 9.4 T.

PMID- 17540287
TI  - Renal subcapsular pseudocyst: findings on MRI.
AB  - Pancreatic pseudocysts are common complications of pancreatitis. They may occur
      in unusual places as a result of spread along the path of least resistance.
      Penetration of Gerota's fascia and spread into the renal subcapsular space are
      uncommon. Their appearance on magnetic resonance imaging has not been previously
      documented. Given the increased use of magnetic resonance
      cholangiopancreatography for the investigation of patients with pancreatitis, the
      recognition that a complicated renal cyst in this clinical context could
      represent a benign condition is important.

PMID- 17540288
TI  - Visual target processing in high- and low-performing older subjects indexed by P3
      component.
AB  - AIM: To explore the possible changes in the parameters of the P3 event-related
      potential (ERP) component among groups of young and older healthy subjects
      characterized as either high- or low-performers in a visual attention task.
      METHODS: Both conventional and single-trial analyses of the visual P3 component
      were performed on each group of subjects. RESULTS: P3 component significantly
      increased in latency as a function of age. The high-performing older subjects
      showed the posterior predominance of P3, as in young subjects. However, the low
      performing older subjects showed a significant P3 amplitude reduction at
      posterior locations and topographically more widespread activity. Furthermore,
      single-trial analysis showed that low-performing older subjects presented higher
      intertrial variability in P3 latency, few trials with P3 generation, and a
      reduced P3 amplitude in these trials in whom P3 was generated. CONCLUSION: These
      data suggest a specific decline in visual target processing in the low-performing
      older subjects, which would imply a reduction in these attentional brain
      resources that are allocated to correctly select the relevant stimuli. The
      implications of this finding for the actual compensation versus dedifferentiation
      debate in normal aging are discussed.

PMID- 17540289
TI  - Right frontal event related EEG coherence (ERCoh) differentiates good from bad
      performers of the Wisconsin Card Sorting Test (WCST).
AB  - AIM: To investigate changes in Event-Related Coherence (ERCoh) associated to good
      and bad resolution of the Wisconsin Card Sorting Test (WCST). METHODS: Event
      Related Potentials (ERPs) were recorded from a sample of 30 university students
      while they performed a computerized version of the WCST. ERCoh was calculated for
      frontal and parietal electrodes for two specific moments: immediately before the
      response and after the feedback cues. RESULTS: Bad performers presented
      significantly reduced ERCoh at the right frontal region (in alpha, beta-1 and
      beta-2 bands), while no consistent group differences emerged for parietal ERCoh.
      Furthermore, the strength of functional coupling (ERCoh) between midfrontal and
      right-frontal electrodes was a good predictor of WCST behavioural parameters,
      such as the percentage of perseverative errors or the number of categories
      achieved. CONCLUSIONS: The results suggest that the right prefrontal cortex is
      specifically involved in executive functions, such as planning and foresight,
      tapped by the WCST. Although the specificity of the WCST to explore frontal
      lesions has been recently questioned, the present findings support that
      prefrontal areas are specifically involved in the successful resolution of the
      test by healthy subjects.

PMID- 17540290
TI  - Impaired fronto-temporal processing of emotion in schizophrenia.
AB  - AIMS: Abnormal emotion processing in schizophrenia affects social and functional
      outcome. Spatiotemporal brain mechanisms underlying this deficit are unclear.
      MATERIALS AND METHODS: Event-related potential (ERP) responses to emotional and
      neutral face processing during an implicit (gender detection) and an explicit
      (expression detection) task were compared between a group of healthy volunteers
      (n=10) and a group of patients with schizophrenia (n=10). RESULTS: Whereas
      patients had normal primary visual cortex responses, the early modulation of
      occipital, temporal, and frontal responses by emotional expression observed in
      controls was absent in patients. The occipito-temporal N170 amplitude was reduced
      in patients relative to controls during expression detection, but not during
      gender detection. Frontal activity within 180-250ms was reduced in patients
      compared to controls. As opposed to controls, no significant difference was seen
      in patients at the right temporal electrode (T6) between amplitudes of long
      latency ERPs elicited by distinct emotions during the expression detection task.
      CONCLUSION: In patients with schizophrenia, abnormal early extraction of
      expression-related information in the occipito-temporal cortex (before 170ms)
      impairs structural encoding of facial expressions (N170) and may disrupt
      motivation- and task-dependent context processing (180-250ms time window) of
      expression-related facial features. Moreover, top-down neuromodulation from
      frontal and limbic structures to visual occipito-temporal cortex may not be
      sufficient to optimize the extraction of expression-specific face features.

PMID- 17540291
TI  - Mismatch negativity in paranoid, schizotypal, and antisocial personality
      disorders.
AB  - AIMS: The mismatch negativity (MMN) to frequency deviant tones has yielded
      conflicting results in patients with schizophrenia. This might be because Axis I
      schizophrenia overlaps with Axis II diagnoses such as paranoid or schizotypal
      personality disorders. This study was designed to address this issue. METHODS: We
      evaluated the auditory MMN to frequency deviance in 17 patients with paranoid, 15
      schizotypal, and 16 antisocial personality disorders. These were compared to 25
      healthy subjects. RESULTS: N1 to both deviant and standard tones was shorter in
      the paranoid group when compared to healthy controls. MMN latencies were shorter
      at Fz, Cz, and Pz in the paranoid group when compared to healthy controls,
      schizotypal, and antisocial groups. MMN amplitudes were higher at Fz and Cz in
      the schizotypal and antisocial groups when compared to healthy controls and the
      paranoid group. CONCLUSIONS: Patients with paranoid personality disorder had
      faster automatic detection of auditory stimuli and of their change, but normal
      inhibition of irrelevant stimuli. By contrast, patients with schizotypal and
      antisocial personality disorders had normal discrimination of the auditory
      stimuli, but might have a deficit in inhibition on irrelevant stimuli. Our
      results might help differentiate these personality types, and clarify some MMN
      findings in schizophrenia.

PMID- 17540292
TI  - Spatial localization of EEG electrodes.
AB  - AIM OF THE STUDY: An important goal for EEG-based functional brain studies is to
      estimate the location of brain sources that produce the scalp-recorded signals.
      Such source localization requires locating precisely the position of the EEG
      sensors. This review describes and compares different methods that are used for
      localizing EEG sensors. RESULTS: Five different methods have been described in
      literature. Manual methods consist in manual measurements to calculate the 3D
      coordinates of the sensors. Electromagnetic and ultrasound digitization permit
      localization by using trade devices. The photogrammetry system consists in taking
      pictures of the patient's head with the sensors. The last method consists in
      directly localizing the EEG sensors in the MRI volume. DISCUSSION AND
      CONCLUSIONS: The spatial localization of EEG sensors is an important step in
      performing source localization. This method should be accurate, fast,
      reproducible, and cheap. Currently, electromagnetic digitization is the most
      currently used method but MRI localization could be an interesting way because no
      additional method or device needs to be used to locate the EEG sensors.

PMID- 17540293
TI  - Managing oral mucositis in patients with haematological malignancies: the
      progress in European centres.

PMID- 17540294
TI  - Ensuring accurate oral mucositis assessment in the European Group for Blood and
      Marrow Transplantation Prospective Oral Mucositis Audit.
AB  - Oral mucositis (OM) has substantial negative clinical, quality-of-life, and
      economic consequences for patients with haematologic malignancies who require
      myeloablative chemotherapy or radiotherapy. Uniform training in OM assessment is
      infrequent in clinical practice, so the true incidence and duration of OM are
      unknown. Nurses and physicians from the European Group for Blood and Marrow
      Transplantation recently undertook an audit of 214 patients (197 evaluable
      patients) treated at 25 centres, the Prospective Oral Mucositis Audit (POMA), to
      determine the incidence, severity, and duration of OM. To standardise the
      assessment of OM severity, the World Health Organization (WHO) Oral Toxicity
      Scale was used across centres. This article focuses on the quality control
      analyses that were conducted to ensure that OM was accurately assessed across all
      25 centres. Twenty-two trainers, who received comprehensive training about POMA
      study design, pathobiology of OM, and endpoint assessment, educated staff at the
      25 transplantation centres about OM assessment. The trained staff collected data
      by completing daily worksheets for each patient. Three quality control analyses,
      of 82, 1949, and 4111 worksheets respectively, showed a nurse assessment accuracy
      rate of 74%, 90%, and 90%. The most common errors were in assigning WHO grade 0
      or 1. This analysis shows that training of nursing staff had a positive effect on
      assessment of OM severity, which should ultimately lead to improvement in the
      quality of supportive care.

PMID- 17540295
TI  - Palifermin for patients with haematological malignancies: shifting nursing
      practice from symptom relief to prevention of oral mucositis.
AB  - Oral mucositis (OM) is an extremely debilitating side effect of certain high-dose
      chemotherapy and radiotherapy regimens. It is especially prevalent in patients
      with haematological malignancies who undergo myeloablative therapy and autologous
      haematopoietic stem cell transplantation (HSCT). Severe erosion of the lining of
      the oral cavity can make patients' everyday activities, including eating,
      drinking, swallowing, and talking, difficult or even impossible. Palifermin
      (Kepivance) was approved in Europe in 2005 for both prevention and treatment of
      this painful condition. It works at the epithelial level to help protect cells in
      the mouth and throat from the damage caused by chemotherapy and radiation, and to
      stimulate growth and development of new epithelial cells to build up the mucosal
      barrier. In the pivotal clinical trial, palifermin reduced the incidence,
      severity, and duration of severe OM. Palifermin was also well-tolerated; common
      adverse reactions reported included rash, pruritus, erythema, edema, pain, fever,
      arthralgia, mouth or tongue disorders, and taste alteration. In this article,
      nurses who are skilled in caring for patients undergoing HSCT review their
      clinical experience with palifermin, sharing practical advice about its
      reconstitution, dosing, and administration. By familiarising themselves with the
      use of palifermin, nurses can influence a shift in clinical practice away from OM
      symptom management to the more satisfactory situation of protecting patients
      against severe OM.

PMID- 17540296
TI  - Management of oral mucositis at European transplantation centres.
AB  - Oral mucositis (OM), which occurs in many patients with hematologic malignancies
      treated with high-dose therapy and stem cell transplantation, is associated with
      substantial clinical, economic, and quality-of-life (QOL) consequences. It has
      been associated with an increased need for total parenteral nutrition and opioid
      analgesics, prolonged hospital stays, and increased risk of infection. The
      research subgroup of the European Group for Blood and Marrow Transplantation
      Nurses Group surveyed nurses at transplantation centres for their thoughts about
      the clinical, QOL, and economic consequences of OM; tools for assessing OM;
      strategies for preventing and treating OM; and the need for the development and
      implementation of treatment guidelines. The responses from 46 centres, in 16
      countries, indicated that most nurses (91%) believe OM has a large effect on
      patients' QOL. Nurses are not highly satisfied with current treatments for OM,
      but they believe the discomfort is reduced with oral care protocols and
      mouthwashes. Oral mucositis is routinely and frequently assessed, however there
      are inconsistencies in how it is managed. Most centres used unpublished, centre
      specific guidelines, and the survey found that most nurses agreed that published
      national guidelines would be valuable for standardising the assessment and
      management of OM.

PMID- 17540297
TI  - Is modern technology increasing our risk of cancer?

PMID- 17540298
TI  - Developmental biology, self-renewal, and cancer.

PMID- 17540299
TI  - The maturation of medical oncology.

PMID- 17540300
TI  - MRC RT01: an important trial.

PMID- 17540301
TI  - Angiogenesis and lung cancer: implications for prognosis and treatment.

PMID- 17540302
TI  - Chemotherapy for advanced NSCLC: any light at the end of the tunnel?

PMID- 17540303
TI  - Opportunities for improving the therapeutic ratio for patients with sarcoma.
AB  - Sarcomas are mesenchymal cancers, which, in many cases, have distinctive
      molecular features. Limb-sparing surgery delivered at specialised sarcoma centres
      as part of a multidisciplinary approach has become the standard treatment for
      most patients and usually provides excellent local control. Preoperative
      treatment with chemotherapy is most common for patients with bone sarcomas. The
      ideal sequence of surgery and radiation for local management of soft-tissue
      sarcoma remains controversial on the basis of early versus late treatment
      complications, although preoperative radiation can provide the best results for
      improved long-term function. New methods for radiation delivery and tumour
      sensitisation might provide further improvements. However, metastatic disease is
      common, and conventional chemotherapy provides for only a narrow therapeutic
      window outside of a few responsive pathological subtypes. Targeting underlying
      molecular events in specific sarcomas can provide for dramatic benefits, as has
      been seen with imatinib treatment for gastrointestinal stromal tumours and
      dermatofibrosarcoma protuberans. Trials of agents targeting the cell cycle and
      angiogenesis in soft-tissue sarcomas, and of those targeting osteoclasts in bone
      sarcomas, are currently underway. Biological data and preclinical studies support
      trials using inhibitors of hedgehog signalling in chondrosarcoma, inhibitors of
      wnt/beta-catenin in osteosarcoma and aggressive fibromatosis, and inhibitors of
      histone deacetylases in synovial sarcoma and Ewing sarcoma. Pharmacogenetic
      approaches will be needed to identify individual determinants of response and
      outcome in order to maximise the benefits of targeting specific molecular events
      and keep side-effects to a minimum. Research in stem-cell biology and
      nanotechnology holds promise for additional novel treatment options in the
      future.

PMID- 17540304
TI  - Abdominal MRI advances in the detection of liver tumours and characterisation.
AB  - With recent technical advances in hardware, software, and intravenous contrast
      agents, MRI has evolved into a clinically useful procedure to detect and
      characterise liver tumours. The combination of MRI systems with larger gradients,
      improved surface coils, and parallel imaging techniques have produced substantial
      improvements in MRI quality and speed of image acquisition. Images that
      previously needed several minutes to acquire can now be obtained in several
      seconds. The notably faster imaging capabilities of new MRI scanners are ideally
      suited for dynamic contrast-enhanced liver imaging in which early arterial-phase
      imaging is best for detecting hepatocellular carcinomas and hypervascular liver
      metastases. The inherent excellent soft-tissue contrast of MRI can be further
      improved by non-specific extracellular contrast agents and by liver-specific
      contrast agents. These contrast agents are now routinely used for liver imaging
      and improve the sensitivity and specificity of hepatobiliary MRI.

PMID- 17540305
TI  - Conflicting priorities in surgical intervention for cancer in pregnancy.
AB  - Cancer in pregnancy is uncommon, with an incidence of about one to two cases in
      every 1000 pregnancies. There are no randomised trials on any aspect of the
      management of cancer in pregnancy. Stage for stage cancer outcomes are similar in
      women who are pregnant compared with those who are not. Misdiagnosis and delayed
      diagnosis are common where the index of suspicion by the mother and health carers
      is low. Surgical interventions pose some risk to the fetus, especially laparotomy
      for abdominal tumours and procedures undertaken during the first trimester.
      Chemotherapy is teratogenic in the early stages, but seems to be safe in later
      pregnancy, and radiotherapy can be used for localised tumours remote from the
      uterus, such as head and neck or limb neoplasms. Suspicious symptoms should be
      appropriately investigated during pregnancy, and recent advances in non-ionising
      radiation staging techniques, such as MRI and ultrasound, are especially helpful.
      Surgical interventions can be safely undertaken with minimum risk, although there
      is almost always some element of maternal-fetal conflict.

PMID- 17540306
TI  - Therapeutic strategies in oesophageal carcinoma: role of surgery and other
      modalities.
AB  - Traditionally, surgery is considered the best treatment for oesophageal cancer in
      terms of locoregional control and long-term survival. However, survival 5 years
      after surgery alone is about 25%, and, therefore, a multidisciplinary approach
      that includes surgery, radiotherapy, and chemotherapy, alone or in combination,
      could prove necessary. The role of each of these treatments in the management of
      oesophageal cancer is under intensive research to define optimum therapeutic
      strategies. In this report we provide an update on treatment strategies for
      resectable oesophageal cancers on the basis of recent published work. Results of
      the latest randomised trials allow us to propose the following guidelines:
      surgery is the standard treatment, to be used alone for stages I and IIa, or
      possibly with neoadjuvant chemotherapy or chemoradiotherapy for stage IIb
      disease. For locally advanced cancers (stage III), neoadjuvant chemotherapy or
      chemoradiotherapy followed by surgery is appropriate for adenocarcinomas.
      Chemoradiotherapy alone should only be considered in patients with squamous-cell
      carcinomas who show a morphological response to chemoradiotherapy, and produces a
      similar overall survival to chemoradiotherapy followed by surgery, but with less
      post-treatment morbidity. Although the addition of surgery to chemotherapy or
      chemoradiotherapy could result in improved local control and survival, surgery
      should be done in experienced hospitals where operative mortality and morbidity
      are low. Moreover, surgery should be kept in mind as salvage treatment in
      patients with no morphological response or persistent tumour after definitive
      chemoradiotherapy.

PMID- 17540307
TI  - TNM staging system for renal-cell carcinoma: current status and future
      perspectives.
AB  - The Tumour, Nodes, and Metastasis (TNM) staging system is a method of stratifying
      patients with cancer and is based on data obtained from large multicentre studies
      that involved large numbers of patients, and have a good level of evidence.
      However, despite continual revisions to the methodology to incorporate evidence
      from new clinical studies, the optimum stratification of patients with renal-cell
      carcinoma (RCC) using the TNM staging system remains controversial and further
      revisions, in our opinion, are needed. Revision of the TNM staging system for
      renal-cell cancer could also result in the simultaneous update of the integrated
      prognostic systems that are currently used along side this traditional method of
      staging. These integrated systems could become key instruments for guiding
      patient counselling, for appropriate follow up strategies, for patient selection
      for clinical trials, and for appropriate assessment of results if the perception
      that they are complex is overcome. This perception is driven by the presence of
      more than one system, the heterogeneity of clinical and pathological variables
      included in the methodology, and the need for robust comparative studies between
      the various systems. Therefore, in everyday clinical practice, the TNM system is
      regarded as a more reliable method of staging. In this Essay, we aim to highlight
      the problems associated with the current version of the TNM staging system and
      highlight areas in which this grading instrument can be improved in future to
      become a more refined and standardised method of communication between all
      clinicians involved in clinical management of RCC.

PMID- 17540308
TI  - EGFR-mutant lung adenocarcinoma in a patient with Li-Fraumeni syndrome.

PMID- 17540309
TI  - [Which optimal antihypertensive bitherapy for kidney patients?].
AB  - In this editorial review on the optimal antihypertensive treatment for chronic
      kidney disease (CKD) patients, we start with the controversy triggered by Casas
      et al., for proposing a bitherapy optimal not only for nephroprotection, but also
      for global cardiovascular protection. The incidence of cardiovascular
      complications are indeed much greater than the occurrence of end stage renal
      disease (ESRD) in these patients, so that their prevention has at least the same
      priority. We explain the huge amount of discordant papers, on the basis of
      methodology deficiencies in the studies aiming at evidencing the truth of 2
      antinomic concepts underlying this controversy: 1) "The correction by
      antihypertensive drugs of the cardiovascular risk excess in hypertensive patients
      is exclusively related to their blood pressure lowering effect, the optimal blood
      pressure (BP) level being defined by epidemiologists at 115/75 mmHg"; 2)
      "Independently of BP lowering effect, antihypertensive drugs may have intrinsic,
      protective or deleterious, renal and cardiovascular effects which may be variable
      according to the target organ". We think that truth is conciliating and that both
      mechanisms should not be exclusive. However more rigorous studies are still
      needed to evidence it. Meanwhile we propose the optimal therapy by hypokaliemic
      diuretics (thiazides+/-loop diuretics according to glomerular filtration
      decline)+inhibitors of the angiotensin AT1-receptor (ACE inhibitors or AT1RB), in
      preference to the association of dihydropyridines with diuretics. This
      recommendation is strong however, only for CKD patients with macroproteinuria.
      The priority that we give to diuretic therapy is based on the evidence that this
      class confers good prevention against both heart failure and strokes, which is
      not the case for all AT1-inhibitors and dihydropyridines. Furthermore the
      diuretics are the drugs with the longest antihypertensive effect (many weeks) and
      their efficiency in CKD patients is proportional to the sodium depletion they
      initially induce and therefore to the dose (specially of the loop diuretics).
      Indeed volemia control is an incontrovertible factor for optimal BP control in
      renal insufficiency. As regards the use of betablockers, they should no more be
      considered as first drug for hypertension because they have the strongest
      diabetogenic effect. They should be used selectively for their specific
      cardiologic indications such as angina, heart failure, arythmia and as substitute
      for ACEI or AT1RB when general anesthesia is considered. Regarding the choice
      between ACEI and AT(1)RB, on the basis of indirect comparisons, we think that the
      latter may grant a comparable cardiac protection while giving a better cerebral
      protection. We shall have to wait the results of ONTARGET study to have or not
      the evidence for this preference. Finally, we want to stress the necessity to
      individualize the treatment by taking into account coexistence of cardiovascular
      complications and of other diseases, as well as the tolerance of the treatment
      (which may be influenced by seasons, in particular the canicula one), and the
      cost of the drugs.

PMID- 17540310
TI  - [Iatrogenic angioedema: the role of angiotensin converting enzyme inhibitor and
      angiotensin II receptor blockers].
AB  - Nephrologists should be aware the fact that the angioedema is a common side
      effect not only under angiotensin-converting enzyme (ACE) inhibitors treatment
      but also under sartans therapy. The frequency of angioedema under ACE inhibitors
      is estimated at 1 to 7 per thousand. The physiopathology of ACE angioedema
      implicates the lack of degradation of kinines due to the inhibition of multiple
      enzymes activity including ACE. Angioedema under sartans seems less frequent than
      this observed under ACE inhibitors. Its mechanism remains poorly defined, but
      implicates the increase of kinine production via the stimulation of angiotensin
      receptor type II, and/or the lack of degradation of kinines via multiple enzymes
      other than ACE. The frequency of the apparition of angioedema under sartans in
      patients who had have angioedema under ACE inhibitors is inconsistent and varied
      from 7.7% to 50%. Reports indicated that angioedema under ACE or sartans could
      have a spontaneous regression. However, the relapse of angioedema under these
      drugs should lead to the diagnosis of iatrogenic etiology, and to the drugs
      withdrawal. ACE inhibitors/Sartans-associated angioedema episodes need to be
      reported to the French Adverse Event Reporting System database to evaluate their
      frequency and to avoid severe consequences.

PMID- 17540311
TI  - [Cost of dialysis in France].
AB  - The provision of care for patients with end-stage chronic renal failure is an
      important medical and economic challenge for the Health Insurance. Previous
      studies have shown a lower cost for home dialysis. More recently, studies have
      confirmed identical short-term survival rates between haemodialysis and
      peritoneal dialysis. Notwithstanding, home dialysis techniques utilization
      remains weak in France. This work aims at: determining the average annual cost of
      dialysis, per patient and per technique of dialysis, and assessing the global
      annual cost of dialysis in France, from the Health Insurance perspective.
      Methodologically, this article provides a static estimation of the cost of
      dialysis. Costs related to co-morbidities of end-stage chronic renal failure have
      not been considered. Standard patient care schemes have been outlined by a
      multidisciplinary expert committee, for each dialysis technique, and have been
      valorised using publicly available data and tariffs recorded in 2005. Our result
      show that home dialysis techniques are the less costly, with an average annual
      cost per patient of 49.9, 49.7 and 50.0 k euro respectively for home
      haemodialysis, automated peritoneal dialysis, and continuous ambulatory
      peritoneal dialysis. Autodialysis, autonomous in-center haemodialysis and in
      center haemodialysis respectively cost 59.5, 62.3 and 81.5 k euro per patient and
      per annum. The total 2005 cost of dialysis for the Health Insurance is estimated
      at 2.1 billion euro. Therefore, the development of alternative techniques to in
      center haemodialysis, such as home dialysis or autonomous in-center
      haemodialysis, autodialysis being already well developed, could generate savings
      for the Health Insurance. From the patient's perspective, it could also allow the
      enlightened choice of the best customized technique, less guided by local offer
      than by medical or social criteria, as well as by the patient's own opinion.

PMID- 17540312
TI  - [A rare cause of peripheral edema: exudative lymphocytic gastritis induced
      hypoprotidemia].
AB  - Diagnosis of edema secondary to hypoprotidemia but without nutritional, renal,
      hepatic or cardiac cause, must consider exudative digestive disease, of which the
      lymphocytic gastritis, as the authors report here a new observation diagnosed in
      a 73 year-old woman. Gastroscopy reveals varioliform gastritis and biopsy
      demonstrates diffuse infiltration of the gastric epithelium by lymphocytes,
      making of it a real histopathologic entity among the gastropathies. Etiology and
      pathogeny remain still unknown but proton pump gastric inhibitors are an
      effective treatment.

PMID- 17540313
TI  - [Alport syndrome or progressive hereditary nephritis with hearing loss].
AB  - Alport syndrome is an inherited disorder characterized by progressive hematuric
      nephritis with structural defects of the glomerular basement membrane, and
      sensorineural deafness. Ocular abnormalities are frequently associated. The
      incidence is approximatively 1/5000. The renal disease is severe in male patients
      and should be responsible for 2% of end-stage renal failure. Alport syndrome is
      heterogeneous at the clinical and genetic levels. It occurs as a consequence of
      structural abnormalities in type IV collagen, the major constituent of basement
      membranes. Six genetically distinct chains of type IV collagen have been
      identified. Mutations in the COL4A5 gene located at Xq22, and encoding the alpha
      5(IV) chain are responsible for X-linked Alport syndrome whereas COL4A3 or COL4A4
      located "head to head" on chromosome 2 are involved in the rarer autosomal forms
      of the disease.

PMID- 17540314
TI  - We've come a long way baby... or have we?

PMID- 17540315
TI  - Jordanian nurses' job satisfaction and intent to stay: comparing teaching and non
      teaching hospitals.
AB  - The aims of this study were to identify variables of Jordanian nurses' job
      satisfaction and intent to stay, compare the phenomena of interest in teaching
      and non-teaching hospitals, and correlate the two concepts of nurses' job
      satisfaction and intent to stay. A convenience sample of 433 nurses was obtained
      from three teaching hospitals and two non-teaching hospitals. Nurses were
      "neither satisfied nor dissatisfied" and were "neutral" in reporting their intent
      to stay at their current jobs. Nurses who were working in non-teaching hospitals
      reported higher job satisfaction and intent to stay rates than those working in
      teaching hospitals. Nurses' job satisfaction and intent to stay were at the
      borderlines, which require the immediate attention of nursing and hospital
      administrators. Nurses' job satisfaction and intent to stay, particularly in
      teaching hospitals, have to be promoted; thus, interventions have to be
      effectively initiated and maintained at the unit and organizational levels.

PMID- 17540316
TI  - Advanced health assessment in nurse practitioner programs: follow-up study.
AB  - The increase in advanced practice graduate programs and the inclusion of content
      and skills related to advanced health assessment as a core competency for
      practice served as the impetus for a 5-year follow-up study to track the changes,
      methodologies, and integration of technology into practitioner programs. The
      questionnaire was mailed to the faculty/schools listed as current members in the
      National Health Service Corps Nurse Practitioner Faculty Advocate Network. The
      number of responding schools was 135 (44%). The family nurse practitioner program
      continues to be the most offered advanced practice nursing program. Nearly all
      institutions offer a post-master's program and an advanced health assessment
      course to their clinical graduate students. Health assessment is usually taught
      concurrently or as a prerequisite for clinical experiences; there continues to be
      a strong emphasis on the physical examination component. Ethnic and cultural
      assessment and gerontological assessment content increased since the original
      study. Both class and laboratory class sizes decreased. Qualitative data that
      centered on differences in graduate versus undergraduate health assessment
      revealed a shift in focus in several areas: differential diagnoses, abnormals,
      and the inclusion of advanced skills. There was an emergence of more creative
      strategies: the use of standardized patients, online coursework, videotaping,
      "live" patients, and simulations.

PMID- 17540317
TI  - Predicting early academic achievement in a baccalaureate nursing program.
AB  - Baccalaureate nursing programs are under increased pressure to graduate greater
      numbers of students to meet the demands of the nurse workforce of the future.
      Schools of nursing are admitting larger cohorts of students, but early academic
      achievement in the nursing major and retention are problematic. Historical
      predictors of early academic achievement, such as scholastic aptitude, may not be
      the best for identifying students at risk of early academic failure.
      Increasingly, baccalaureate nursing programs are relying on standardized nursing
      aptitude tests to evaluate the readiness of applicants for the nursing major.
      However, reliable predictors of early academic achievement have yet to be
      identified. The purpose of this study was to explore whether scholastic aptitude
      and nursing aptitude are predictive of early academic achievement in a
      baccalaureate nursing program. Using an exploratory descriptive design, data from
      164 sophomore nursing students were examined. The data indicated that scholastic
      aptitude and nursing aptitude together predicted 20.2% of the variance in early
      academic achievement, with scholastic aptitude accounting for 15.4% of the
      variance.

PMID- 17540318
TI  - Use of the innovation-decision process teaching strategy to promote evidence
      based practice.
AB  - The purpose of this article is to describe the innovation-decision process
      teaching strategy (I-DPTS) based on the model of diffusion of innovations
      [Rogers, E. M. (2003). Diffusion of innovations (5th ed.). New York: Free Press].
      A goal of baccalaureate nursing education is to develop competencies required for
      evidence-based practice. Such practice merges clinician expertise, patient
      preferences, and critical evaluation of the literature to improve patient
      outcomes and reduce health care costs [Melnyk, B. M. (2005). A primer on evidence
      based practice. Paper presented at the Purdue School of Nursing Seventh Annual
      Helen R. Johnson Leadership Conference, West Lafayette, IN]. Several strategies
      to promote evidence-based practice have appeared in the literature. However, when
      they are examined in light of the innovation-decision process (Rogers, 2003),
      they do not address all the essential steps for adoption to occur. The I-DPTS
      allows students to achieve competencies necessary to overcome barriers associated
      with implementing best practices. This strategy was successfully implemented in a
      senior-level introductory nursing research class. Community representatives
      identified practice issues that could be addressed by student groups. After
      conducting a search of the literature, students analyzed the evidence, determined
      best practice based on the evidence, and developed a policy for implementation in
      clinical settings. At course end, representatives were invited to attend oral and
      poster presentations. Use of the I-DPTS better prepares students to implement
      best practice as they embark on their professional careers.

PMID- 17540319
TI  - Conflict management styles in the health professions.
AB  - The purpose of the study was to determine prevalent conflict management styles
      chosen by students in nursing and to contrast these styles with those chosen by
      students in allied health professions. The associations among the level of
      professional health care education and the style chosen were also determined. A
      convenience sample of 126 students in a comprehensive university completed the
      Thomas-Kilmann Conflict Mode Instrument (TKI), which requires respondents to
      choose behaviors most characteristic of their response to conflict and classifies
      these behaviors as one of five styles. There was no significant difference
      between the prevalent conflict management styles chosen by graduate and
      undergraduate nursing students and those in allied health. Some of the students
      were already licensed in their discipline; others had not yet taken a licensing
      exam. Licensure and educational level were not associated with choice of styles.
      Women and men had similar preferences. The prevalent style for nursing students
      was compromise, followed by avoidance. In contrast, avoidance, followed by
      compromise and accommodation, was the prevalent style for allied health students.
      When compared to the TKI norms, slightly more than one half of all participants
      chose two or more conflict management styles, commonly avoidance and
      accommodation at the 75th percentile or above. Only 9.8% of the participants
      chose collaboration at that level. Implications for nurse educators, researchers,
      and administrators are discussed.

PMID- 17540320
TI  - There really is a difference: nurses' experiences with transitioning from RNs to
      BSNs.
AB  - The purpose of this phenomenological study was to explore and describe the
      experience that associate degree and diploma nursing graduates have when
      transitioning from RN to BSN. Twelve nurses with a variety of clinical
      backgrounds and completion of different RN-BSN programs were interviewed to
      elicit the lived experience of transitioning from RN to BSN. Eight theme clusters
      emerged when the formulated meanings were organized into categories: (1) Varied
      Expectations, (2) Tentative Beginnings, (3) Cornerstone Courses, (4) Translating
      Knowledge Into Empowerment, (5) Becoming Assertive Leader and Advocate, (6)
      Confronting and Conquering Challenges, (7) Envisioning the Whole, and (8)
      Recreating Everyday Practice. Findings indicate that both the quality of patient
      care and nurses' practice were enhanced as a result of BSN completion programs.

PMID- 17540321
TI  - The humanities interface of nursing and medicine.
AB  - In the 1970s, the field of medical humanities developed and included ethics,
      literature, history, integrative medicine, and other topics, most often described
      from a physician's perspective. During this same period of revolutionary changes
      in health care, nursing curricula did not seek to emphasize content in
      humanities, perhaps because stereotypical views of nursing as the "caring
      profession" made such coursework seem redundant. In 2001, as a result of the
      Institute of Medicine's call for all health professionals to be educated in
      interdisciplinary teams, there was a new focus on the importance of
      interdisciplinary education. Collaborative experiences in the humanities can
      foster professional relationships that lead to professional growth, promote
      collaboration, and enhance patient-centered care. The purpose of this article is
      to describe the relevance of humanities to the interdisciplinary education and
      practice of health care providers. This article extends the thinking about the
      value of interdisciplinary education beyond the traditional dimensions of
      evidence-based practice, quality improvement, and informatics to humanities. Ways
      to provide nurses and physicians with interdisciplinary humanistic experiences
      are illustrated through an overview of projects jointly developed by the School
      of Nursing and the College of Medicine at The Pennsylvania State University.

PMID- 17540322
TI  - Promoting collaboration in nursing education: the development of a regional
      simulation laboratory.
AB  - This article describes a collaboratively developed plan for a regional patient
      simulation laboratory for nursing education. The Western North Carolina Regional
      Simulation Laboratory will be located at the Enka Campus of the Asheville
      Buncombe Technical Community College at the Department of Nursing of Western
      Carolina University (Candler, NC). A proactive collaborative consortium has been
      established to help meet the demand for nursing education in the 13 most rural
      mountain counties of western North Carolina. Through a 2-year process with
      regional networking, the nursing administration of Western Carolina University,
      Mission Hospitals, Asheville-Buncombe Technical Community College, and affiliated
      community colleges, consortium hospitals, and emergency care services developed a
      vision and a proposal for an innovative program for the nursing education of the
      future. The consortium proposed the establishment of a 3-year integrated
      educational program utilizing state-of-the-art simulation manikin technology.
      Financial resources were obtained from a charitable grant from The Duke Endowment
      (Charlotte, NC). Sustainability of funding will be ensured through university,
      hospital, and community college collaboration.

PMID- 17540323
TI  - Quantitative predictive modelling of ultrafiltration processes: colloidal science
      approaches.
AB  - Membrane ultrafiltration is a separation process of considerable industrial
      importance. The specification and optimisation of such processes require the
      development of good predictive methods. This article reviews the development of a
      range of such methods based on fundamental descriptions of colloidal interactions
      and hydrodynamics, especially those close to the membrane surface. Particle
      particle interactions may be efficiently calculated using a cell-model
      description of electrostatic interactions coupled with appropriate quantification
      of London-van der Waals forces and the entropic pressure. The overall
      interactions may be described in terms of osmotic pressures, which further
      facilitate calculation of the corresponding gradient diffusion coefficients.
      Methods for the calculation of the local solution viscosity are also described.
      Excellent agreement with experimental data is obtained when these calculated
      properties are incorporated in mathematical models describing either frontal
      ultrafiltration of cross-flow ultrafiltration. The predictive calculations may be
      used in a number of different ways, depending on the level of knowledge of the
      colloidal properties available. For example, at the most fundamental level the
      pressure dependence of the rate of cross-flow ultrafiltration of a protein may be
      calculated from a knowledge of the protein sequence.

PMID- 17540324
TI  - Intraocular pressure and foveal thickness after phacoemulsification.
AB  - PURPOSE: To evaluate the natural course of intraocular pressure (IOP) and foveal
      thickness during the postoperative period, and the correlation between them.
      DESIGN: Prospective observational case series. METHODS: This institutional study
      comprised 30 eyes of 30 cataract patients scheduled for phacoemulsification. IOP
      and foveal thickness by optical coherence tomography (OCT) were measured
      preoperatively and three, six, nine, 12, 15, 18, 21, 24 hours, five days, one
      month, and two months postoperatively. RESULTS: The IOP was 4.7 +/- 2.4 mm Hg at
      three hours postoperatively. The IOP increased to 23.4 +/- 8.1 mm Hg at six hours
      and 23.5 +/- 7.3 mm Hg at nine hours postoperatively. The IOP was 1.9 mm Hg lower
      at one month or two months postoperatively than preoperatively. The foveal
      thickness was 202.1 +/- 19.2 microm and significantly higher at three hours
      postoperatively, and was 182.3 +/- 20.5 microm, 183.2 +/- 22.3 microm, and
      significantly lower at nine and 12 hours postoperatively than preoperatively. The
      correlation between mean IOP and mean foveal thickness is statistically
      significant. Fovea thickness (microns) = 207.0476 - 1.019759 x IOP (mm Hg), P
      value < .0001, adjusted R(2) = .8699. CONCLUSIONS: We found initial hypotony, an
      IOP spike during six to nine hours, and a decrease of IOP at one month and two
      months postoperatively. An initial increase of the foveal thickness, a
      significant reduction at nine hours and 12 hours, and an equivocal increase at
      one month or two months postoperatively were also noted. A significant negative
      correlation between IOP and foveal thickness was shown.

PMID- 17540325
TI  - A multienzyme bioluminescent time-resolved pyrophosphate assay.
AB  - We have developed a high-sensitivity assay for measurement of inorganic
      pyrophosphate (PPi) in adenosine 5'-triphosphate (ATP)-contaminated samples. The
      assay is based on time-resolved measurements of the luminescence kinetics and
      implements multiple enzymes to convert PPi to ATP that is, in turn, utilized to
      produce light and to hydrolyze PPi for measurement of the steady state background
      luminescence. A theoretical model for describing luminescence kinetics and
      optimizing composition of the assay detection mixture is presented. We found that
      the model is in excellent agreement with the experimental results. We have
      developed and evaluated two algorithms for PPi measurement from luminescence
      kinetics acquired from ATP-contaminated samples. The first algorithm is
      considered to be the method of choice for analysis of long, i.e., 3-5 min,
      kinetics. The activity of enzymes is controlled during the experiment; the
      sensitivity of PPi detection is about 7 pg/ml or 15 pM of PPi in ATP-contaminated
      samples. The second algorithm is designed for analysis of short, i.e., less than
      1-min, luminescence kinetics. It has about 20 pM PPi detection sensitivity and
      may be the better choice for assays in microplate format, where a short
      measurement time is required. The PPi assay is primarily developed for RNA
      expression analysis, but it also can be used in various applications that require
      high-sensitivity PPi detection in ATP-contaminated samples.

PMID- 17540326
TI  - Increase in bioluminescence intensity of firefly luciferase using genetic
      modification.
AB  - Firefly luciferase is widely used for enzymatic measurement of ATP, and its gene
      is used as a reporter for gene expression experiments. From our mutant library,
      we selected novel mutations in Photinus pyralis luciferase with higher
      luminescence intensity. These included mutations at Ile423, Asp436, and Leu530.
      Luciferase is structurally composed of a large N-terminal active site domain
      (residues 1-436), a flexible linker (residues 436-440) peptide, and a small C
      terminal domain (residues 440-550) facing the N domain. Thus, the mutations are
      located at the junction of the N-terminal domain and the flexible linker, in the
      flexible linker peptide, and in the tip of the C-terminal domain, respectively.
      Substitution of Asp436 with a nonbulky amino acid such as Gly remarkably
      increased the substrate affinity for ATP and d-luciferin. Substitution of Ile423
      with a hydrophobic amino acid such as Leu and that of Leu530 with a positively
      charged amino acid such as Arg increased the substrate affinity and the turnover
      rate. Combining these mutations, we obtained luciferases that generate more than
      10-fold higher luminescence intensity than the wild-type enzyme.

PMID- 17540327
TI  - Elimination of vertical streaking in polyacrylamide gel electrophoresis.

PMID- 17540328
TI  - Production of bioactive peptides in an in vitro system.
AB  - An in vitro system for the preparation of bioactive peptides is described. This
      system couples three different posttranslational modification enzymes, prohormone
      convertases (PCs), carboxypeptidase E, and peptidyl alpha-amidating enzyme, to
      transform recombinant precursors into bioactive peptides. Three different
      precursors, mouse proopiomelanocortin (mPOMC), rat proenkephalin (rPE), and human
      proghrelin, were used as model systems. The conversion of mPOMC and rPE to
      smaller peptide products was measured by radioimmunoassay. After optimization of
      the system, excellent efficiency was obtained: about 85% of starting mPOMC was
      converted to des-acetyl alpha-melanocyte-stimulating hormone (alpha-MSH). For
      proenkephalin, 75 and 96% yields were obtained for the opioid peptides Met-RGL
      and Met-enk, respectively. Cell-based assays demonstrated that in-vitro-generated
      des-acetyl alpha-MSH successfully activated the melanocortin 4 receptor.
      Proghrelin digestion was used to screen the specificity of PC cleavage and to
      confirm the cleavage site by mass spectroscopy. Mature ghrelin was produced by
      human furin, mouse prohormone convertase 1, and human prohormone convertase 7 but
      not by mouse prohormone convertase 2. These results demonstrate that our in vitro
      system (1) can produce peptides in quantities sufficient to carry out functional
      analyses, (2) can be used to determine the specificity of proprotein convertases
      on recombinant precursors, and (3) has the potential to identify novel peptide
      functions on both known and orphan G-protein-coupled receptors.

PMID- 17540329
TI  - Peptide analysis: solid phase extraction-elution on diamond combined with
      atmospheric pressure matrix-assisted laser desorption/ionization-Fourier
      transform ion cyclotron resonance mass spectrometry.
AB  - Electrospray ionization (ESI) has been an indispensable ion generation technique
      for mass spectrometric analysis of biopolymers such as intact proteins and
      protein digests operated at atmospheric pressure. Since its advent in 1998,
      atmospheric pressure matrix-assisted laser desorption/ionization (AP-MALDI)
      quickly became a popular alternative for the analysis of peptides. Although AP
      MALDI sources typically share the same vacuum interface and ion transmission
      hardware with ESI, it is generally found that ESI is superior in detection
      sensitivity. Here we present a method based on solid phase extraction and elution
      with surface-functionalized diamond nanocrystals (which we previously referred to
      as "SPEED") that not only streamlines AP-MALDI mass spectrometric analyses of
      peptides and other small biomolecules under typical operational conditions but
      also outruns ESI in ultimate detectable concentration by at least one order of
      magnitude.

PMID- 17540330
TI  - Detection of insulin-releasing cells using in situ immunoblotting.
AB  - Embryonic stem (ES) cells hold promise as a source for cell transplantation
      treatment of diseases such as type I diabetes. Further, cells releasing bioactive
      substances from ES cell progeny may be concentrated and purified for clinical
      applications. Although ES cell lines that express reporter genes have been
      established to isolate cells releasing bioactive substances, other difficulties
      must be overcome before these genetically modified cells can be used for gene
      therapy in human patients. Fluorescence- or magnetic-activated cell sorters are
      commonly used to isolate specific cells using antibodies against cell surface
      antigens. However, for some cells, such as insulin-producing beta cells, specific
      surface antigens have not yet been identified. In this study, we developed a
      simple and efficient method to identify and purify insulin- and alpha-fetoprotein
      producing cells. A nitrocellulose membrane treated with anti-insulin or anti
      alpha-fetoprotein antibodies was placed on a cell layer to trap insulin or alpha
      fetoprotein released from the cells. The location of specific substance-producing
      cells was identified by immunostaining the membrane. The insulin-releasing cells
      were selectively collected from the culture dish using a cloning ring and
      transferred to another culture plate.

PMID- 17540331
TI  - Subcellular proteomics of mice gastrocnemius and soleus muscles.
AB  - A proteomics characterization of mice soleus and gastrocnemius white portion
      skeletal muscles was performed using nuclear, mitochondrial/membrane, and
      cytosolic subcellular fractions. The proposed methodology allowed the elimination
      of the cytoskeleton proteins from the cytosolic fraction and of basic proteins
      from the nuclear fraction. The subsequent protein separation by two-dimensional
      gel electrophoresis prior to mass spectrometry analysis allowed the detection of
      more than 600 spots in each muscle. In the gastrocnemius muscle fractions, it was
      possible to identify 178 protein spots corresponding to 108 different proteins.
      In the soleus muscle fractions, 103 different proteins were identified from 253
      positive spot identifications. A bulk of cytoskeleton proteins such as actin,
      myosin light chains, and troponin were identified in the nuclear fraction,
      whereas mainly metabolic enzymes were detected in the cytosolic fraction.
      Transcription factors and proteins associated with protein biosynthesis were
      identified in skeletal muscles for the first time by proteomics. In addition,
      proteins involved in the mitochondrial redox system, as well as stress proteins,
      were identified. Results confirm the potential of this methodology to study the
      differential expressions of contractile proteins and metabolic enzymes, essential
      for generating functional diversity of muscles and muscle fiber types.

PMID- 17540332
TI  - Development of dual-enzyme-based simultaneous immunoassay for measurement of
      progesterone and human chorionic gonadotropin.
AB  - The development of a simultaneous multianalyte immunoassay for the detection of
      progesterone and human chorionic gonadotropin (hCG) in serum is described. In
      this simultaneous multianalyte assay, two different enzymes, viz. horse radish
      peroxidase (HRP) and alkaline phosphatase (ALP), were used as markers. To the
      simultaneous immobilized progesterone and hCG antibody microwells, 50 microL of
      different concentrations of combined standards or serum samples was added in
      duplicate and then 100 microL of combined conjugate reagent, composed of 17-alpha
      OH-P-ALP and hCG-biotin was added to all the wells and incubated for 1h at 37
      degrees C. After incubation, the contents of the wells were decanted and washed
      thoroughly with running tap water. After washing, 100 microL alkaline phosphatase
      substrate along with streptavidin-horseradish peroxidase was added to all the
      wells and incubated for 0.5 h at 37 degrees C. After incubation, the developed
      color was measured at 405 nm. The absorbency at this stage provides the result
      for the progesterone assay. The contents of the wells were decanted and washed.
      In the next step, 100 microL of tetramethylbenzidene/H2O2 reagent was added to
      all the wells. After 15 min of incubation, 100 microL of 0.5 M H2SO4 was added to
      all the wells and the color was read at 450 nm. The absorbency at this stage
      provides the result for the hCG assay. Sensitivity of the progesterone and hCG
      assays were 0.118 ng/ml and 0.124 IU/ml respectively. Intra- and inter assay
      percentage coefficients of variation ranged from 1.8 to 7.1 and 9.1 to 11.5 for
      progesterone and from 2.1 to 10.4 and 7.2 to 11.3 for hCG. There was good
      correlation between the discrete and the simultaneous assays. For progesterone
      assay, R2 was 0.99 and for hCG R2 was also 0.99. The developed dual assay for
      progesterone and hCG may be useful for the diagnosis of abnormal pregnancies such
      as miscarriages and ectopic pregnancies.

PMID- 17540333
TI  - Characterization of weak protein dimerization by direct analysis of sedimentation
      equilibrium distributions: the INVEQ approach.
AB  - Closer scrutiny has been accorded a recently reported procedure for
      characterizing weak protein dimerization by sedimentation equilibrium (INVEQ) in
      which the equilibrium distribution is analyzed as a dependence of radial distance
      on solute concentration rather than of solute concentration on radial distance.
      By demonstrating theoretically that the fundamental parameter derived from the
      analysis is simply the difference between the dimerization constant and the
      osmotic second virial coefficient for monomer-monomer interaction, this
      investigation refutes the original claim that independent estimates of these two
      parameters can be obtained by nonlinear curve fitting of the sedimentation
      equilibrium distribution. This criticism also applies to conventional analyses of
      sedimentation distributions by the commonly employed Beckman Origin and NONLIN
      software. Numerically simulated distributions are then analyzed to demonstrate
      limitations of the procedure and also to indicate a means of improving the
      reliability of the returned estimate of the dimerization constant. These features
      are illustrated by applying the original and revised analytical procedures to a
      sedimentation equilibrium distribution for alpha-chymotrypsin (pH 4.0, I 0.05 M).

PMID- 17540334
TI  - Using high-performance liquid chromatography to measure the effects of protein
      stabilizing cosolvents on a model protein and fluorescent probes.
AB  - The effect of cosolvents on the fluorescence of solutes was measured manually and
      in an automated high-performance liquid chromatography (HPLC) system that
      eliminates fluorescent contaminants on-line. The HPLC system was used to show
      that the effect of cosolvents on the fluorescence spectrum of heated chymotrypsin
      (a measure of unfolding) correlates with the effect of the solutes on the heat
      stabilization of catalytic activity; r2=0.73 with 12 example cosolvents. Changes
      in the fluorescence of model probes showed that known counteracting solutes
      slightly decrease the polarity of the solvent. Different cosolvents affect the
      proton transfer indicator, 2-naphthol (a model for tyrosinyl residues)
      differently, polyhydric alcohols enhance the protonated naphthol emission whereas
      zwitterionic solutes enhance naphthoxide fluorescence. The results with the
      automated system are consistent with the known stabilizing effects of the
      cosolvents and validate it as a tool to explore the development of novel
      cosolvents and their effects on multiple biological systems.

PMID- 17540335
TI  - Prolactinoma and estrogens: pregnancy, contraception and hormonal replacement
      therapy.
AB  - The stimulatory role of estrogen on prolactin secretion and on proliferation of
      lactotropic cells is well established in terms of physiology but could this
      phenomenon be extended to include harmful effects of estrogens on prolactinoma?
      The aim of this review is to provide an up-to-date assessment of this subject
      with regard to pregnancy, use of contraceptive pills and postmenopausal hormone
      replacement therapy. Dopamine agonists allow women presenting prolactinoma to
      recover their ovulation cycles and become pregnant. There is no adverse data
      concerning the safety of dopamine agonists such as bromocriptine, if the woman is
      treated during the first trimester of pregnancy but there is little information
      regarding the most recent treatments such as cabergoline or quinagolide. In women
      with microadenomas, pregnancy generally has little impact on their adenoma,
      delivery is normal and breast-feeding is allowed. Concerning macroprolactinomas,
      tumor progression during pregnancy is possible and endocrine follow-up remains
      necessary. Contraceptive pills containing estrogen and progestins are currently
      the best-tolerated and the most effective contraception. This type of
      contraceptive has long been avoided in patients presenting prolactinoma. While
      the literature has little to say on this subject and provides no adverse
      information, professional experience suggests that this attitude should be
      amended and that women presenting microprolactinoma should be allowed to use
      current contraceptive pills (containing 30 microg or less of ethinyl estradiol).
      The most important problem to overcome with this type of prescription, which
      masks the clinical consequences of hyperprolactinemia, is the possibility of
      overlooking hypophyseal disease that could result from this approach. The problem
      of macroprolactinoma is different; the possibility of prescribing contraceptive
      pills must be evaluated on a case-by-case basis and the impact of the drug on the
      adenoma must be very closely monitored. Estrogen replacement therapy in patients
      presenting hypogonadism should be attempted in patients with a history of
      prolactinoma and standard-monitoring precautions should be taken. In menopausal
      women, when replacement therapy is desirable, the presence of a microprolactinoma
      should not by itself avoid this prescription.

PMID- 17540336
TI  - Structural insight into the altered substrate specificity of human cytochrome
      P450 2A6 mutants.
AB  - Human P450 2A6 displays a small active site that is well adapted for the
      oxidation of small planar substrates. Mutagenesis of CYP2A6 resulted in an
      increased catalytic efficiency for indole biotransformation to pigments and
      conferred a capacity to oxidize substituted indoles (Wu, Z.-L., Podust, L.M.,
      Guengerich, F.P. J. Biol. Chem. 49 (2005) 41090-41100.). Here, we describe the
      structural basis that underlies the altered metabolic profile of three mutant
      enzymes, P450 2A6 N297Q, L240C/N297Q and N297Q/I300V. The Asn297 substitution
      abolishes a potential hydrogen bonding interaction with substrates in the active
      site, and replaces a structural water molecule between the helix B'-C region and
      helix I while maintaining structural hydrogen bonding interactions. The
      structures of the P450 2A6 N297Q/L240C and N297Q/I300V mutants provide clues as
      to how the protein can adapt to fit the larger substituted indoles in the active
      site, and enable a comparison with other P450 family 2 enzymes for which the
      residue at the equivalent position was seen to function in isozyme specificity,
      structural integrity and protein flexibility.

PMID- 17540337
TI  - The phosphatase activity of the plasma membrane Ca2+ pump. Activation by acidic
      lipids in the absence of Ca2+ increases the apparent affinity for Mg2+.
AB  - The purified PMCA supplemented with phosphatidylcholine was able to hydrolyze
      pNPP in a reaction media containing only Mg(2+) and K(+). Micromolar
      concentrations of Ca(2+) inhibited about 75% of the pNPPase activity while the
      inhibition of the remainder 25% required higher Ca(2+) concentrations. Acidic
      lipids increased 5-10 fold the pNPPase activity either in the presence or in the
      absence of Ca(2+). The activation by acidic lipids took place without a
      significant change in the apparent affinities for pNPP or K(+) but the apparent
      affinity of the enzyme for Mg(2+) increased about 10 fold. Thus, the stimulation
      of the pNPPase activity of the PMCA by acidic lipids was maximal at low
      concentrations of Mg(2+). Although with differing apparent affinities vanadate,
      phosphate, ATP and ADP were all inhibitors of the pNPPase activity and their
      effects were not significantly affected by acidic lipids. These results indicate
      that (a) the phosphatase function of the PMCA is optimal when the enzyme is in
      its activated Ca(2+) free conformation (E2) and (b) the PMCA can be activated by
      acidic lipids in the absence of Ca(2+) and the activation improves the
      interaction of the enzyme with Mg(2+).

PMID- 17540338
TI  - Cardiac-specific activation of Cre expression at late fetal development.
AB  - In a first step towards dissecting molecular mechanisms that contribute to the
      development of cardiac diseases, we have generated transgenic mice that express a
      Cre-GFP fusion protein under the transcriptional control of a 4.3kb murine
      cardiac Troponin I gene (cTnI) promoter. Cre-GFP expression, similar in three
      transgenic lines, is described in one line. In mouse embryos, transgenic for the
      Cre-GFP and ROSA lacZ reporter allele, first Cre-mediated recombination appeared
      at 16.5 dpc selectively at the heart. Like the endogenous cTnI gene, transgenic
      Cre expression showed a slow rise through fetal development that increased
      neonatally. Bitransgenic hearts, stained at 30 days of age, showed intense
      signals in ventricular and atrial myocytes while no recombination occurred in
      other tissues. The delayed onset of Cre activity in cTnI-Cre mice could provide a
      useful genetic tool to evaluate the function of loxP targeted cardiac genes
      without interference of recombination during early heart development.

PMID- 17540339
TI  - The isolated polycystin-1 COOH-terminal can activate or block polycystin-1
      signaling.
AB  - Much of what is known of the activities of polycystin-1 has been inferred from
      the effects of the isolated cytoplasmic COOH-terminal domain, but it is not clear
      whether the truncation acts like polycystin-1, as a dominant negative, or in
      unrelated pathways. To address this question, we have examined functional
      interactions between the intact and truncated forms of polycystin-1 in one cell
      system. In cells expressing only native polycystin-1, introduction of the
      truncation replicated the activity of the full-length protein. Conversely, when
      background levels of polycystin-1 were modestly elevated, the truncation acted as
      a dominant negative. Hence, the truncation acts in the polycystin pathway, but
      with effects that depend upon the background level of polycystin-1 expression.
      Our data raise the possibility that the cytoplasmic carboxyl terminus, either
      through cleavage products or intramolecular interactions, might feed back to
      modulate the activity of parent or intact polycystin-1.

PMID- 17540340
TI  - Reduced secretion and expression of gelatinase profile in Toxoplasma gondii
      infected human monocytic cells.
AB  - The apicomplexan Toxoplasma gondii, an obligate intracellular parasite, can
      infect humans and a wide range of vertebrates. Following oral infection, the
      parasite invades tissues by crossing non-permissive biological barriers such as
      the placenta or the blood-brain barrier. But the molecular mechanisms underlying
      migration of T. gondii remain poorly characterized. The crossing of various basal
      membranes and infiltration into the extracellular matrix by T. gondii could
      involve matrix metalloproteinases (MMPs). We demonstrated a decrease in proMMP-2
      and proMMP-9 secretion by THP-1 cells at 24 and 48h post invasion with regulation
      at the mRNA level throughout infection. This down regulation was associated with
      a decrease in TIMP-2 secretion and an inhibition of its expression. Moreover,
      results showed an activation of MT1-MMP; its expression was regulated after 6,
      24, and 48h.

PMID- 17540342
TI  - Bidirectional membrane molecule transfer between dendritic and T cells.
AB  - The acquisition of dendritic cell (DC) molecules by T cells has been previously
      reported. However, it remains unclear whether the transfer is only mono- or
      bidirectional. In this study, we incubated CMFDA-labeled ovalbumin (OVA)-pulsed
      DC2.4 (DC2.4(OVA)) cells with Dil-labeled OT II CD4(+) T cells and analyzed the
      potential bidirectional molecule transfer. We also assessed the distribution of
      internalized membrane using two engineered DC2.4/Ia(b)GFP and MF4/TCRCFP DC
      lines. Our findings showed that membrane molecule transfer is bidirectional.
      CD4(+) T cells acquired Ia(b), CD11c, CD40, and CD80 from DC2.4(OVA) cells, and
      conversely DC2.4(OVA) cells took up CD4, CD25, CD69, and T cell receptor from T
      cells. The internalized molecules acquired by T cells and DCs mostly localized in
      endosomes and lysosomes, respectively. Taken together, this study demonstrated a
      novel phenomenon of bidirectional membrane molecule transfer between DCs and T
      cells.

PMID- 17540341
TI  - NADPH binding to beta-subunit regulates inactivation of voltage-gated K(+)
      channels.
AB  - Ancillary beta-subunits regulate the voltage-dependence and the kinetics of Kv
      currents. The Kvbeta proteins bind pyridine nucleotides with high affinity but
      the role of cofactor binding in regulating Kv currents remains unclear. We found
      that recombinant rat Kvbeta 1.3 binds NADPH (K(d)=1.8+/-0.02 microM) and NADP(+)
      (K(d)=5.5+/-0.9 microM). Site-specific modifications at Tyr-307 and Arg-316
      decreased NADPH binding; whereas, K(d) NADPH was unaffected by the R241L
      mutation. COS-7 cells transfected with Kv1.5 cDNA displayed non-inactivating
      currents. Co-transfection with Kvbeta1.3 accelerated Kv activation and
      inactivation and induced a hyperpolarizing shift in voltage-dependence of
      activation. Kvbeta-mediated inactivation of Kv currents was prevented by the
      Y307F and R316E mutations but not by the R241L substitution. Additionally, the
      R316E mutation weakened Kvalpha-beta interaction. Inactivation of Kv currents by
      Kvbeta:R316E was restored when excess NADPH was included in the patch pipette.
      These observations suggest that NADPH binding is essential for optimal
      interaction between Kvalpha and beta subunits and for Kvbeta-induced inactivation
      of Kv currents.

PMID- 17540343
TI  - Inhibition of gut pacemaker cell formation from mouse ES cells by the c-kit
      inhibitor.
AB  - Using an embryoid body (EB) culture system, we developed a functional organ-like
      cluster, a "gut", from mouse embryonic stem (ES) cells (ES gut). Each ES gut
      exhibited various types of spontaneous movements. In these spontaneously
      contracting ES guts, dense distributions of interstitial cells of Cajal (ICC) (c
      kit, a transmembrane receptor that has tyrosine kinase activity, positive cells;
      gut pacemaker cells) and smooth muscle cells were discernibly identified. By
      adding Glivec 10(-5)M, a tyrosine kinase receptor c-kit inhibitor, only during EB
      formation, we for the first time succeeded in suppressing in vitro formation of
      ICC in the ES gut. The ES gut without ICC did not exhibit any movements. However,
      it appeared that Glivec 10(-6)-10(-7)M rather increased number of ES guts with
      spontaneous movements associated with increase of intracellular Ca(2+)
      concentration ([Ca(2+)](i)). These results suggest ICC is critical for in vitro
      formation of ES guts with spontaneous movements.

PMID- 17540344
TI  - Relevance of extracellular and intracellular interactions of camptothecins as
      determinants of antitumor activity.
AB  - Camptothecins are potent antitumor agents that stabilize the covalent binding of
      topoisomerase I to DNA forming a reversible ternary complex which, following
      collision with the replication forks, converts the single-strand breaks into
      lethal double-strand breaks. This cytotoxic mechanism has been originally
      ascribed to the closed lactone form, because opening of the lactone ring resulted
      in loss of antitumor activity. Since the lipophilic lactone favours passive
      diffusion into the cancer cells, the stability of the closed form is expected to
      be predictive for activity. Thus, the in vivo pharmacological behavior of
      camptothecins, which is dependent on the pH-dependent dynamics, is likely a
      critical determinant of their antitumor efficacy and therapeutic index. The
      physicochemical properties could influence a number of cellular and in vivo
      interactions, including stability of the ternary DNA-enzyme-drug complex, binding
      to serum proteins, recognition by transport systems. These interactions are also
      implicated in the processes responsible of toxic side effects and drug resistance
      which are major limitations of the efficacy of camptothecin-based therapy. A
      number of strategies have been developed to overcome the limitations associated
      with the peculiar in vivo reactivity and the reversibility of drug-target
      interaction. Modifications with hydrophilic or lipophilic substituents at
      specific positions may have a variable (and somewhat opposite) influence on
      interaction with the intracellular target and plasma proteins and on recognition
      by membrane transporters. Here, we highlight the interactions of camptothecins
      which could be exploited to optimize therapeutic efficacy.

PMID- 17540345
TI  - Irreversible binding of a novel phenylisothiocyanate tropane analog to monoamine
      transporters in rat brain.
AB  - Irreversible tropane analogs have been useful in identifying binding sites of
      cocaine on biogenic amine transporters, including transporters for dopamine
      (DAT), serotonin (SERT) and norepinephrine (NET). The present study characterizes
      the properties of the novel phenylisothiocyanate tropane HD-205, synthesized from
      the highly potent 2-napthyl tropane analog WF-23. In radioligand binding studies
      in brain membranes, direct IC(50) values of HD-205 were 4.1, 14 and 280nM at DAT,
      SERT and NET, respectively. Wash-resistant binding was characterized by
      preincubation of HD-205 with brain membranes, followed by extensive washing
      before performing transporter radioligand binding. Results for HD-205 showed wash
      resistant IC(50) values of 191, 230 and 840nM at DAT, SERT and NET, respectively.
      Saturation binding studies with [(125)I]RTI-55 in membranes pretreated with 100nM
      HD-205 showed that HD-205 significantly decreased the B(max) but not K(D) of DAT
      and SERT binding. To further characterize its irreversible binding, an iodinated
      analog of HD-205, HD-244, was prepared from a trimethylsilyl precursor. The
      direct IC(50) of HD-244 at DAT was 20nM. [(125)I]HD-244 was synthesized with
      chloramine-T, purified on HPLC, reacted with rat striatal membranes, and proteins
      were separated by SDS-PAGE. Results showed several non-specific labeled bands,
      but only a single specific band of radioactivity co-migrating with an
      immunoreactive DAT band at approx. 80 kilodaltons was detected, suggesting that
      [(125)I]HD-244 covalently labeled DAT protein in striatal membranes. These
      results demonstrate that phenylisothiocyanate analogs of WF-23 can be used as
      potential ligands to map distinct binding sites of cocaine analogs at DAT.

PMID- 17540346
TI  - Roles of peripheral terminals of transient receptor potential vanilloid-1
      containing sensory fibers in spinal cord stimulation-induced peripheral
      vasodilation.
AB  - BACKGROUND: Spinal cord stimulation (SCS) is used to relieve ischemic pain and
      improve peripheral blood flow in selected patients with peripheral arterial
      diseases. Our previous studies show that antidromic activation of transient
      receptor potential vanilloid-1 (TRPV1) containing sensory fibers importantly
      contributes to SCS-induced vasodilation. OBJECTIVES: To determine whether
      peripheral terminals of TRPV1 containing sensory fibers produces vasodilation
      that depends upon the release of calcitonin gene-related peptide (CGRP) and
      nitric oxide (NO) during SCS. METHODS: A unipolar ball electrode was placed on
      the left dorsal column at lumbar spinal cord segments 2-3 in sodium pentobarbital
      anesthetized, paralyzed and ventilated rats. Cutaneous blood flow from left and
      right hindpaws was recorded with laser Doppler flow perfusion monitors. SCS was
      applied through a ball electrode at 30%, 60%, 90% and 300% of motor threshold.
      Resiniferatoxin (RTX; 2 microg/ml, 100 microl), an ultra potent analog of
      capsaicin, was injected locally into the left hindpaw to functionally inactivate
      TRPV-1 containing sensory terminals. In another set of experiments, CGRP(8-37),
      an antagonist of the CGRP-1 receptor, was injected at 0.06, 0.12 or 0.6 mg/100
      microl into the left hindpaw to block CGRP responses; N-omega-nitro-l-arginine
      methyl ester (L-NAME), a nonselective nitric-oxide synthase (NOS) inhibitor, was
      injected at 0.02 or 0.2 mg/100 microl into the left hindpaw to block nitric oxide
      synthesis; (4S)-N-(4-Amino-5[aminoethyl]aminopentyl)-N'-nitroguanidine, TFA, a
      neuronal NOS inhibitor, was injected at 0.02 or 0.1 mg/100 microl into the left
      hindpaw to block neuronal nitric oxide synthesis. RESULTS: SCS at all intensities
      produced vasodilation in the left hindpaw, but not in the right. RTX
      administration attenuated SCS-induced vasodilation at all intensities in the left
      hindpaw (P<0.05, n=7) compared with responses before RTX. CGRP(8-37)
      administration attenuated SCS-induced vasodilation in the left hindpaw in a dose
      dependent manner (linear regression, P<0.05) compared with responses before
      CGRP(8-37). In addition, L-NAME at a high dose, but not (4S)-N-(4-Amino
      5[aminoethyl]aminopentyl)-N'-nitroguanidine, TFA, decreased SCS-induced
      vasodilation (P<0.05, n=5). CONCLUSION: While TRPV1, CGRP and NO are known to be
      localized in the same nerve terminals, our data indicate that SCS-induced
      vasodilation depends on CGRP release, but not NO release. NO, released from
      endothelial cells, may be associated with vascular smooth muscle relaxation and
      peripheral blood flow increase in response to SCS.

PMID- 17540347
TI  - Prenatal stress generates deficits in rat social behavior: Reversal by oxytocin.
AB  - Neurodevelopmental changes induced by environmental stress exposure play a
      significant but poorly defined role in the etiology of schizophrenia. Exposure of
      pregnant female rats to a series of unpredictable stresses during the final week
      of pregnancy generates behavioral deficits and molecular changes in the offspring
      similar to those observed in schizophrenic individuals. We used this rat prenatal
      stress preparation to investigate social withdrawal behaviors that may have
      relevance to the negative symptoms of schizophrenia. The cumulative time adult
      male offspring of stress-exposed pregnant female rats actively interacted with a
      weight-matched, same-sex peer was decreased approximately 76% relative to non
      stress exposed control rats. Prenatal stress exposure also diminished the quality
      of the social interaction behavior indicative of reduced social drive. Analysis
      of the oxytocinergic system in the prenatally stressed male rats revealed
      significantly less oxytocin mRNA in the paraventricular nucleus and increased
      oxytocin receptor binding in the central amygdala. Moreover, oxytocin, but not
      vasopressin, administration into the central amygdala reversed the social
      incompetence of the prenatally stressed rats without increasing behavior in non
      stressed control animals. In addition, cross-fostering pups from prenatally
      stressed mothers to non-stressed mothers failed to improve the social deficit of
      the prenatally stressed male offspring. Two behavioral assays designed to measure
      anxiety did not differentiate the prenatally stressed rats from non-stressed
      controls. These data indicate that prenatal stress may be an etiologically
      appropriate animal model for some aspects of schizophrenic social withdrawal.
      Furthermore, unpredictable prenatal stress exposure selectively degrades social
      interaction behaviors without increasing anxiety measures.

PMID- 17540348
TI  - Phase-dependent roles of reactive microglia and astrocytes in nervous system
      injury as delineated by imaging of peripheral benzodiazepine receptor.
AB  - Elevated levels of peripheral benzodiazepine receptor (PBR) in glia have been
      documented in diverse nervous system injuries, while the identity and
      spatiotemporal characteristics of the cells showing upregulation of PBR remain
      elusive. We examined the astrocytic and microglial expressions of PBR in rat
      brains during the duration of ethanol-induced neuronal insults in order to
      clarify the significance of PBR as a biomarker capable of detecting a distinctive
      subpopulation of these glial cells involved in the impairment and protection of
      neurons. The levels of PBR, as determined by autoradiographic analysis using a
      specific radioligand, [11C]DAA1106, began to significantly increase at 3 days
      after intrastriatal injection of ethanol, and peaked at 7 days. This was
      consistent with the results of double immunofluorescence staining and high
      resolution emulsion autoradiography, which revealed upregulation of PBR in both
      microglia and astrocytes proliferating in nonoverlapping compartments of the
      injury site. Notably, increased expression of PBR in astrocytes was transiently
      observed in a manner parallel to the centripetal migration of these cells to the
      inflammatory lesion, which may be a response indispensable to the protection of
      intact tissue. Thereafter, astrocytic PBR was barely detectable, despite the
      presence of numerous glial fibrillary acidic protein-immunoreactive astrocytes
      forming glial scarring. By contrast, intense PBR signals were persistently
      present in microglia localized to the injury epicenter up to 90 days,
      notwithstanding a gradual reduction in the number of ionized calcium binding
      adapter molecule-1-positive amoeboid microglia between 7 and 90 days. The long
      lasting PBR expression in microglia was finally supported by in vivo positron
      emission tomography imaging, and suggests that inflammatory tissue damage is
      potentially expandable unless it is tightly sealed by astrocytic scar. The
      present findings collectively support the utility of PBR in identifying a unique
      temporal pattern of astrocytic and microglial activation that conventional glial
      markers hardly pursue.

PMID- 17540349
TI  - Interactions between higher and lower visual areas improve shape selectivity of
      higher level neurons-explaining crowding phenomena.
AB  - Recent theories of visual perception propose that feedforward cortical processing
      enables rapid and automatic object categorizations, yet incorporates a limited
      amount of detail. Subsequent feedback processing highlights high-resolution
      representations in early visual areas and provides spatial detail. To verify this
      hypothesis, we separate the contributions of feedforward and feedback signals to
      the selectivity of cortical neurons in a neural network simulation that is
      modeled after the hierarchical feedforward-feedback organization of cortical
      areas. We find that in such a network the responses of high-level neurons can
      initially distinguish between low-resolution aspects of objects but are 'blind'
      to differences in detail. After several feedback-feedforward cycles of
      processing, however, they can also distinguish between objects that differ in
      detail. Moreover, we find that our model captures recent paradoxical results of
      crowding phenomena, showing that spatial detail that is lost in visual crowding
      is nevertheless able to evoke specific adaptation effects. Our results thus
      provide an existence proof of the feasibility of novel theoretical models and
      provide a mechanism to explain various psychophysical and physiological results.

PMID- 17540350
TI  - A histologically derived stereotaxic atlas and substance P immunohistochemistry
      in the brain of the least shrew (Cryptotis parva) support its role as a model
      organism for behavioral and pharmacological research.
AB  - Chemotherapy is an effective treatment but difficult to tolerate due to side
      effects like vomiting. Studies on the etiology of chemotherapy-related emesis
      have implicated brainstem nuclei and the neurotransmitter substance P, among
      other substrates. Since rodents do not vomit, other species have been necessary
      as alternative models of chemotherapy-induced emesis. Of these, the least shrew
      (Cryptotis parva) has proven valuable due to its small size, hardiness, and close
      phylogenetic relationship with primates. However, very little neuroanatomical
      data on C. parva exist. We used histological and immunohistochemical techniques
      to provide neuroanatomical data to help validate C. parva as a model organism,
      especially for emesis research. Brains were sectioned and stained for Nissl
      substance or myelin, or immunofluorescently labeled for substance P. Sections
      were photographed, traced, and reconstructed with standardized zero points, and
      these data used to create a stereotaxic atlas. The brain of C. parva was similar
      to but smaller than other mammalian brains, with the cerebellum and hippocampus
      demonstrating the biggest differences. Differences appeared to be related to the
      small size of the brain and the metabolic compromises required of such a small
      mammal. Substance P-like immunoreactivity (SPL-IR) was semiquantitatively mapped,
      and correlated very well with SPL-IR observed in other species. Dense SPL-IR
      areas included the periaqueductal grey, trigeminal nuclei, dorsal raphe, and
      emesis-related brainstem nuclei including the area postrema and solitary tract
      nucleus. These data demonstrate that the anatomical differences between C. parva
      and other mammals will not preclude its use as a model organism.

PMID- 17540351
TI  - Simultaneous observation of superficial cortical and intracerebral microvessels
      in vivo during reperfusion after transient forebrain ischemia in rats using
      synchrotron radiation.
AB  - Using a newly developed angiography system that combines monochromatic
      synchrotron radiation (MSR) as an X-ray source with a high-definition camera or
      video system, we observed superficial cortical and intracerebral microvessels
      simultaneously in vivo during reperfusion after transient forebrain ischemia.
      Transient brain ischemia was induced by 10-min four-vessel occlusion in rats
      under general anesthesia. Angiographic images were then sequentially obtained at
      3 frames/s. The detector features a 7-microm equivalent pixel size projected onto
      the input area and a 7 mmx7 mm input field. Changes in the cerebral microvessels
      were observed before and 1, 5, 10, 15, 20 and 30 min after transient cerebral
      ischemia using the MSR angiography system. The calibers of the internal carotid
      artery (ICA), middle cerebral artery (MCA), and striate artery (SA) significantly
      increased 1 min after reperfusion, while the pial arteriole (PA) caliber
      significantly decreased (76% of base line). The MCA, PA and SA were significantly
      dilated 5 and 10 min after reperfusion. Although the caliber of the ICA
      significantly decreased after 30 min reperfusion compared with the basal value,
      the calibers of the other three vessels remained larger than the basal values
      throughout the experiment. Early venous filling was observed at 5 and 10 min
      after reperfusion. The MSR angiography system is useful for investigating
      morphological changes in both cortical and central branches of cerebral vessels
      in rats during reperfusion after cerebral ischemia.

PMID- 17540352
TI  - Sphingolipids with neuritogenic activity from Euphorbia sororia.
AB  - Two groups of sphingolipids 1 and 2 were isolated from the aerial parts of
      Euphorbia sororia. On the basis of spectroscopic data, chemical methods and GC-MS
      analysis, the structures of 1 and 2 were characterized as 1-O-beta-D
      glucopyranosyl-(2S,3S,4R,8Z)-2-[(2'R)-2'-hydroxydocosanoyl approximately
      hexacosanoyl, octacosanoyl amino]-1,3,4-octadecanetriol-8-ene and (2S,3S,4R,8E)-2
      [(2'R)-2'-hydroxyeicosanoyl approximately hexacosanoyl amino]-1,3,4
      octadecanetriol-8-ene, respectively. Both of them exhibited marked neuritogenic
      activity on the rat pheochromocytoma PC12 cell line.

PMID- 17540353
TI  - Intrinsic frames of reference and egocentric viewpoints in scene recognition.
AB  - Three experiments investigated the roles of intrinsic directions of a scene and
      observer's viewing direction in recognizing the scene. Participants learned the
      locations of seven objects along an intrinsic direction that was different from
      their viewing direction and then recognized spatial arrangements of three or six
      of these objects from different viewpoints. The results showed that triplets with
      two objects along the intrinsic direction (intrinsic triplets) were easier to
      recognize than triplets with two objects along the study viewing direction (non
      intrinsic triplets), even when the intrinsic triplets were presented at a novel
      test viewpoint and the non-intrinsic triplets were presented at the familiar test
      viewpoint. The results also showed that configurations with the same three or six
      objects were easier to recognize at the familiar test viewpoint than other
      viewpoints. These results support and develop the model of spatial memory and
      navigation proposed by Mou, McNamara, Valiquette, and Rump [Mou, W., McNamara, T.
      P., Valiquiette C. M., & Rump, B. (2004). Allocentric and egocentric updating of
      spatial memories. Journal of Experimental Psychology: Learning, Memory, and
      Cognition, 30, 142-157].

PMID- 17540354
TI  - Older, not younger, children learn more false facts from stories.
AB  - Early school-aged children listened to stories that contained correct and
      incorrect facts. All ages answered more questions correctly after having heard
      the correct fact in the story. Only the older children, however, produced story
      errors on a later general knowledge test. Source errors did not drive the
      increased suggestibility in older children, as they were better at remembering
      source than were the younger children. Instead, different processes are involved
      in learning correct and incorrect facts from fictional sources. All ages
      benefited from hearing correct answers because they activated a pre-existing
      semantic network. Older children, however, were better able to form memories of
      the misinformation and thus showed greater suggestibility on the general
      knowledge test.

PMID- 17540355
TI  - Simultaneous presentation of soft tissue and bone tissue in computed tomography
      with combined window.
AB  - OBJECTIVES: To examine whether in computed tomography (CT) soft tissue and bone
      tissue can be simultaneously presented with a combined window without loss of
      diagnostic information compared to the separate presentations with soft tissue
      and bone tissue windows. MATERIALS AND METHODS: Forty-seven CT examinations from
      different patients with pathological changes at the soft tissue or bone tissue
      after an accident or due to malignant tumour were evaluated. The CT data were
      transformed into grey level data with three different windows: (1) soft tissue
      window; (2) bone tissue window to show spongiosa and bone cortex; and (3) special
      window to show ethmoidal sinus and mastoidal cells. The images were then weighted
      with a weighting factor of 2, 3 and 1, respectively, resulting in one image with
      combined window. This image was compared with the conventional soft tissue and
      bone tissue images. RESULTS: All diagnostic information could be obtained and
      anatomical details be recognized on the image with combined window. In some cases
      soft tissue structures could be delineated from each other or from adjacent bone
      better on this image than on the soft tissue image. CONCLUSIONS: Combined window
      could enable a reduction of film consumption or digital storage because soft
      tissue and bone tissue are presented on the same image and not separately. The
      risk for overlooking important pathological changes might be reduced as both
      tissues are always presented.

PMID- 17540356
TI  - Neural induction in the absence of organizer in salamanders is mediated by MAPK.
AB  - Research on the mechanisms of embryonic induction had a great setback in the
      1940s when Barth discovered and Holtfreter confirmed that ectoderm of Ambystoma
      maculatum salamander embryos could form brain tissue when cultured in a simple
      saline solution. We have revisited this classical experiment and found that when
      cultured animal cap ectoderm attaches to a glass substratum, it can self-organize
      to form complex organs such as brain vesicles, eyes, lens and olfactory placodes.
      Only anterior neural organs were generated. Under these culture conditions ERK
      became diphosphorylated, indicating a sustained activation of the Ras/MAPK
      pathway. Using sand particles as an example of a heterologous neural inducer
      similar results were obtained. Addition of U0126, a specific antagonist of MEK,
      the enzyme that phosphorylates ERK/MAPK, inhibited neural differentiation. The
      closely related control compound U0124 had no effect. We conclude that neural
      induction in the absence of organizer in A. maculatum requires Ras/MAPK
      activation. These findings provide a molecular explanation for the activity of
      heterologous neural inducers that dominated thinking in amphibian experimental
      embryology for many decades.

PMID- 17540357
TI  - Sequential expression and redundancy of Pitx2 and Pitx3 genes during muscle
      development.
AB  - The myogenic program is controlled by different groups of transcription factors
      acting during muscle development, including bHLH muscle regulatory factors
      (MRFs), the paired factors Pax3 and Pax7 and the homeobox factors Six1 and Six4.
      This program is critically dependent on MRFs that target downstream muscle
      specific genes. We now report the expression of Pitx2 and Pitx3 transcription
      factors throughout muscle development. Pitx2 is first expressed in muscle
      progenitor cells of the dermomyotome and myotome. The onset of myoblast
      differentiation is concomitant with expression of Pitx3; its expression is
      maintained in all skeletal muscles while Pitx2 expression decreases thereafter.
      We have generated Pitx3 mutant mice and this deficiency does not significantly
      perturb muscle development but it is completely compensated by the maintenance of
      Pitx2 expression in all skeletal muscles. These experiments suggest that Pitx
      genes are important for myogenesis and that Pitx2 and Pitx3 may have partly
      redundant roles.

PMID- 17540358
TI  - Cell type-autonomous and non-autonomous requirements for Dmrt1 in postnatal
      testis differentiation.
AB  - Genes containing the DM domain, a conserved DNA binding motif first found in
      Doublesex of Drosophila and mab-3 of Caenorhabditis elegans, regulate sexual
      differentiation in multiple phyla. The DM domain gene Dmrt1 is essential for
      testicular differentiation in vertebrates. In the mouse, Dmrt1 is expressed in
      pre-meiotic germ cells and in Sertoli cells, which provide essential support for
      spermatogenesis. Dmrt1 null mutant mice have severely dysgenic testes in which
      Sertoli cells and germ cells both fail to differentiate properly after birth.
      Here we use conditional gene targeting to identify the functions of Dmrt1 in each
      cell type. We find that Dmrt1 is required in Sertoli cells for their postnatal
      differentiation, and for germ line maintenance and for meiotic progression. Dmrt1
      is required in germ cells for their radial migration to the periphery of the
      seminiferous tubule where the spermatogenic niche will form, for mitotic
      reactivation and for survival beyond the first postnatal week. Thus Dmrt1
      activity is required autonomously in the Sertoli and germ cell lineages, and
      Dmrt1 activity in Sertoli cells is also required non-autonomously to maintain the
      germ line. These results demonstrate that Dmrt1 plays multiple roles in
      controlling the remodeling and differentiation of the juvenile testis.

PMID- 17540360
TI  - EAST and Chromator control the destruction and remodeling of muscles during
      Drosophila metamorphosis.
AB  - Metamorphosis involves the destruction of larval, the formation of adult and the
      transformation of larval into adult tissues. In this study, we demonstrate the
      role of the Drosophila nuclear proteins EAST and Chromator in tissue destruction
      and remodeling. To better understand the function of east, we performed a yeast
      two-hybrid screen and identified the euchromatin associated protein Chromator as
      a candidate interactor. To analyze the functional significance of our two-hybrid
      data, we generated a set of novel pupal lethal Chro alleles by P-element
      excision. The pupal lethal Chro mutants resemble lethal east alleles as
      homozygous mutants develop into pharates with normal looking body parts, but fail
      to eclose. The eclosion defect of the Chro alleles is rescued in an east
      heterozygous background, indicating antagonistic genetic interactions between the
      two genes. Live cell imaging was applied to study muscle development during
      metamorphosis. Consistent with the eclosion defects, mutant pharates of both
      genes show loss and abnormal differentiation of adult eclosion muscles. The two
      genes have opposite effects on the destruction of larval muscles in
      metamorphosis. While Chro mutants show incomplete histolysis, muscles degenerate
      prematurely in east mutants. Moreover east mutants affect the remodeling of
      abdominal larval muscles into adult eclosion muscles. During this process, loss
      of east interferes with the spatial coordination of thinning of the larval
      muscles. Overexpression of EAST-GFP can prevent the disintegration of polytene
      chromosomes during programmed cell death. We propose that Chro activates and east
      inhibits processes and genes involved in tissue destruction and remodeling.

PMID- 17540359
TI  - Identification and characterization of a novel Schwann and outflow tract
      endocardial cushion lineage-restricted periostin enhancer.
AB  - Periostin is a fasciclin-containing adhesive glycoprotein that facilitates the
      migration and differentiation of cells that have undergone epithelial-mesenchymal
      transformation during embryogenesis and in pathological conditions. Despite the
      importance of post-transformational differentiation as a general developmental
      mechanism, little is known how periostin's embryonic expression is regulated. To
      help resolve this deficiency, a 3.9-kb periostin proximal promoter was isolated
      and shown to drive tissue-specific expression in the neural crest-derived Schwann
      cell lineage and in a subpopulation of periostin-expressing cells in the cardiac
      outflow tract endocardial cushions. In order to identify the enhancer and
      associated DNA binding factor(s) responsible, in vitro promoter dissection was
      undertaken in a Schwannoma line. Ultimately a 304-bp(peri) enhancer was
      identified and shown to be capable of recapitulating 3.9 kb(peri-lacZ)in vivo
      spatiotemporal patterns. Further mutational and EMSA analysis helped identify a
      minimal 37-bp region that is bound by the YY1 transcription factor. The 37-bp
      enhancer was subsequently shown to be essential for in vivo 3.9 kb(peri-lacZ)
      promoter activity. Taken together, these studies identify an evolutionary
      conserved YY1-binding 37-bp region within a 304-bp periostin core enhancer that
      is capable of regulating simultaneous novel tissue-specific periostin expression
      in the cardiac outflow-tract cushion mesenchyme and Schwann cell lineages.

PMID- 17540361
TI  - A switch in the cellular basis of skeletogenesis in late-stage sea urchin larvae.
AB  - Primary mesenchyme cells (PMCs) are solely responsible for the skeletogenesis
      during early larval development of the sea urchin, but the cells responsible for
      late larval and adult skeletal formation are not clear. To investigate the origin
      of larval and adult skeletogenic cells, I first performed transplantation
      experiments in Pseudocentrotus depressus and Hemicentrotus pulcherrimus, which
      have different skeletal phenotypes. When P. depressus PMCs were transplanted into
      H. pulcherrimus embryos, the donor phenotype was observed only in the early
      larval stage, whereas when secondary mesenchyme cells (SMCs) were transplanted,
      the donor phenotype was observed in late and metamorphic larvae. Second, a
      reporter construct driven by the spicule matrix protein 50 (SM50) promoter was
      introduced into fertilized eggs and their PMCs/SMCs were transplanted. In the
      resultant 6-armed pluteus, green fluorescent protein (GFP) expression was
      observed in both PMC and SMC transplantations, suggesting SMC participation in
      late skeletogenesis. Third, transplanted PMCs or SMCs tagged with GFP were
      analyzed by PCR in the transgenic chimeras. As a result, SMCs were detected in
      both larval and adult stages, but GFP from PMCs was undetectable after
      metamorphosis. Thus, it appears that SMCs participate in skeletogenesis in late
      development and that PMCs disappear in the adult sea urchin, suggesting that the
      skeletogenesis may pass from PMCs to SMCs during the late larval stage.

PMID- 17540362
TI  - PTEN modulates GDNF/RET mediated chemotaxis and branching morphogenesis in the
      developing kidney.
AB  - The RET receptor tyrosine kinase is activated by GDNF and controls outgrowth and
      invasion of the ureteric bud epithelia in the developing kidney. In renal
      epithelial cells and in enteric neuronal precursor cells, activation of RET
      results in chemotaxis as Ret expressing cells invade the surrounding GDNF
      expressing tissue. One potential downstream signaling pathway governing RET
      mediated chemotaxis may require phosphatidylinositol 3-kinase (PI3K), which
      generates PI(3,4,5) triphosphate. The PTEN tumor suppressor gene encodes a
      protein and lipid phosphatase that regulates cell growth, apoptosis and many
      other cellular processes. PTEN helps regulate cellular chemotaxis by antagonizing
      the PI3K signaling pathway through dephosphorylation of phosphotidylinositol
      triphosphates. In this report, we show that PTEN suppresses RET mediated cell
      migration and chemotaxis in cell culture assays, that RET activation results in
      asymmetric localization of inositol triphosphates and that loss of PTEN affects
      the pattern of branching morphogenesis in developing mouse kidneys. These data
      suggest a critical role for the PI3K/PTEN axis in shaping the pattern of
      epithelial branches in response to RET activation.

PMID- 17540363
TI  - Analysis of large scale expression sequenced tags (ESTs) from the anural
      ascidian, Molgula tectiformis.
AB  - Anural ascidians show embryogenesis during which tail formation does not take
      place. This mode of development is a derived character acquired several times
      independently in ascidian evolution. We identified approximately 20,000 each ESTs
      (i. e. 10,000 clones each were sequenced from both 5' and 3' ends) of adult
      gonads, cleaving-embryos, gastrulae/neurulae, embryos before hatching, and
      hatched larvae of the anural ascidian Molgula tectiformis, in order to
      comprehensively investigate the molecular mechanism of tailless evolution.
      Analyses of these ESTs showed that in this species, (1) the expression of
      embryonic/larval muscle structural genes which are expressed abundantly during
      embryogenesis of the urodele ascidian Ciona intestinalis, is suppressed; (2)
      genes that encode proteins with no similarity to known proteins of other
      organisms are abundantly expressed; (3) genes that show similarity with those up
      regulated at metamorphosis in urodele ascidians are up-regulated within several
      hours after hatching; and (4) 15 of 35 putative orthologues of the downstream
      components of Brachyury, a key transcription factor for ascidian notochord
      formation, were found in the ESTs, even though differentiation of notochord is
      suppressed in this species. We discuss these remarkable results that allow
      insight into the molecular mechanism(s) responsible for the anural mode of
      ascidian development.

PMID- 17540364
TI  - The regulation of Sox9 gene expression by the GATA4/FOG2 transcriptional complex
      in dominant XX sex reversal mouse models.
AB  - We have previously established an in vivo requirement for GATA4 and FOG2
      transcription factors in sexual differentiation. Fog2 null mouse fetuses or
      fetuses homozygous for a targeted mutation in Gata4 (Gata4(ki)), which cripples
      the GATA4-FOG2 interaction, exhibit a profound and early block in testis
      differentiation in both sexes. Others have shown that XX mice with the Ods
      transgenic insertion or the Wt1-Sox9 YAC transgene overexpress the testis
      differentiation gene, Sox9. Thus, these XX animals undergo dominant sex reversal
      by developing into phenotypically normal, but sterile, males. Now we have
      determined that Fog2 haploinsufficiency prevents (suppresses) this dominant sex
      reversal and Fog2+/-Wt1-Sox9 or Ods XX animals develop normally--as fertile
      females. The suppression of sex reversal in Fog2 heterozygous females results
      from approximately 50% downregulation of the expression from the transgene
      associated allele of Sox9. The GATA4/FOG2-dependent sex reversal observed in the
      transgenic XX gonads has to rely on gene targets other than the Y chromosome
      linked Sry gene. Importantly, Fog2 null or Gata4(ki/ki) embryos (either XX or XY)
      fail to express detectable levels of Sox9 despite carrying the Ods mutation or
      Wt1-Sox9 transgene. Fog2 haploinsufficiency leads to a decreased amount of SOX9
      positive cells in XY gonads. We conclude that FOG2 is a limiting factor in the
      formation of a functional GATA4/FOG2 transcription complex that is required for
      Sox9 expression during gonadogenesis.

PMID- 17540365
TI  - Pulmonary endothelium dependent vasodilation emerges after birth in mice.
AB  - At birth, with the first breath, pulmonary vessels undergo profound adaptive
      processes. A failure in the ability of pulmonary vessels to adapt at birth
      results in persistent pulmonary hypertension of the new born. The mechanisms
      regulating pulmonary adaptation at birth are still unclear. Progress in this area
      is slow, not least because genetically modified mice have not yet been used to
      address questions in this area of research, principally because pulmonary vessels
      in new born mice are very small making the study of dilator response in vitro
      difficult. In the current study we have used precision cut lung slices to
      characterise the functional vasomotor changes in lung vessels of new born mice (1
      4 days old), 8-15 day old mice or adult mice. The internal luminal area of
      pulmonary artery and airways was measured digitally. Vasoconstriction and
      vasodilatation were expressed as the percentage change in internal luminal area
      compared with the control area. The thromboxane A(2) mimetic U-46619 (3x10(-7) M)
      caused a significant vasoconstriction in vessels of all groups. However,
      acetylcholine (3x10(-5) M) induced arterial dilation only in the 8-15 days, and
      adult groups. By contrast, sodium nitroprusside, which acts independently of the
      endothelium, was an effective vasodilator in lung vessels from neonates. These
      data are the first to characterise the development of endothelium dependent
      vasodilatation in lung after birth in mice. This approach can be used with
      genetically modified mice, which is important to further our understanding of the
      physiology in this area.

PMID- 17540366
TI  - Emodin, an anthraquinone derivative from Rheum officinale Baill, enhances
      cutaneous wound healing in rats.
AB  - Emodin (1, 3, 8-trihydroxy-6-methyl-anthraquinone) is an anthraquinone derivative
      from the roots of Rheum officinale Baill, a Chinese herb widely and traditionally
      used for wound healing. Our objective was to determine whether topically applied
      emodin enhanced repair of rats' excisional wounds and its possible mechanism.
      Wounds were treated with either topical emodin (100, 200 and 400 microg/ml),
      recombinant human epidermal growth factor (rhEGF, 10 microg/ml), or vehicle for 7
      or 14 days consecutively. At day 5 postinjury, wounds receiving emodin (400
      microg/ml) were significantly smaller than those treated with vehicle. Emodin
      treatments had markedly more hydroxyproline content in day 7 wounds and tensile
      strength in day 14 wounds than that of vehicle control. The level of transforming
      growth factor- beta(1) (TGF-beta(1)) in wound tissues assessed by
      immunohistochemistry and reverse transcription polymerase chain reaction (RT
      PCR), showed a dose-dependent increase in emodin-treated wounds compared with
      vehicle. Western immunoblotting analysis of wound tissues for Smad 2, 3, 4, 7
      protein expression showed increase in Smad 2, 3 in the emodin-treated wounds
      compared with vehicle. In contrast, a reduction of Smad 7 was observed in emodin
      treated wounds compared with vehicle and no change of Smad 4. In summary, our
      results showed that emodin promoted repair of rats' excisional wounds via a
      complex mechanism involving stimulation of tissue regeneration and regulating
      Smads-mediated TGF-beta(1) signaling pathway.

PMID- 17540367
TI  - Methylation-dependent silencing of CST6 in primary human breast tumors and
      metastatic lesions.
AB  - CST6 is a breast tumor suppressor gene that is expressed in normal breast
      epithelium, but is epigenetically silenced as a consequence of promoter
      hypermethylation in metastatic breast cancer cell lines. In the current study, we
      investigated the expression and methylation status of CST6 in primary breast
      tumors and lymph node metastases. 25/45 (56%) primary tumors and 17/20 (85%)
      lymph node metastases expressed significantly lower levels of cystatin M compared
      to normal breast tissue. Bisulfite sequencing demonstrated CST6 promoter
      hypermethylation in 11/23 (48%) neoplastic lesions analyzed, including 3/11 (27%)
      primary tumors and 8/12 (67%) lymph node metastases. In most cases (12/23, 52%),
      the expression of cystatin M directly reflected CST6 promoter methylation status.
      In remaining lesions (8/23, 35%) loss of cystatin M was not associated with CST6
      promoter hypermethylation, indicating that other mechanisms can account for loss
      of CST6 expression. These results show that methylation-dependent silencing of
      CST6 occurs in a subset of primary breast cancers, but more frequently in
      metastatic lesions, possibly reflecting progression-related genomic events. To
      examine this possibility, primary breast tumors and matched lymph node metastases
      were analyzed. In 2/3 (67%) patients, primary tumors were positive for cystatin M
      and negative for CST6 promoter methylation, and matched metastatic lesions lacked
      cystatin M expression and CST6 was hypermethylated. This observation suggests
      that progression-related epigenetic alterations in CST6 gene expression can
      accompany metastatic spread from a primary tumor site. Overall, the results of
      the current investigation suggest that methylation-dependent epigenetic silencing
      of CST6 represents an important mechanism for loss of CST6 during breast
      tumorigenesis and/or progression to metastasis.

PMID- 17540368
TI  - Matrix metalloproteinase-3 (stromelysin-1) in acute inflammatory tissue injury.
AB  - Mice lacking matrix metalloproteinase-3 (MMP-3; stromelysin-1) demonstrated
      significantly less injury than their normal counterparts following the formation
      of IgG-containing immune complexes in the alveolar wall or in the wall of the
      peritoneum. Likewise, mice lacking MMP-3 demonstrated less lung injury following
      intra-tracheal instillation of the chemotactic cytokine macrophage inhibitory
      protein-2 (MIP-2) than did mice with MMP-3. There was a relationship between
      tissue injury (evidenced histologically) and accumulation of anti-laminin 111
      immunoreactive material in the bronchoalveolar lavage (BAL) or peritoneal lavage
      (PL) fluid. There was also a relationship between tissue injury and influx of
      neutrophils into the BAL or PL fluid. Taken together, these data demonstrate an
      important role for MMP-3 in acute inflammatory tissue injury.

PMID- 17540370
TI  - Sex-specific mediation of foraging in the shore crab, Carcinus maenas.
AB  - Experiments were conducted to investigate the sex-specific differences to feeding
      responses of the shore crab Carcinus maenas throughout the year. Results
      demonstrate that female shore crabs exhibit stronger feeding responses than males
      throughout the year with a significantly reduced feeding response in males during
      the summer months' reproductive season. We also studied the possible function(s)
      of the moulting hormone, 20-hydroxyecdysone (Crustecdysone) that has been
      described as a potential female-produced sex pheromone to initiate male
      reproductive behaviour in a number of crustaceans. We recently presented evidence
      that for shore crabs this is not the case and now show that the steroid is
      instead functioning as a sex-specific feeding deterrent protecting the moulting
      'soft' female crabs. Whilst male shore crabs were deterred from prey (Mytilus
      edulis) and synthetic feeding stimulants glycine and taurine when these feeding
      stimulants were spiked with crustecdysone, intermoult female crabs were
      significantly less affected and rarely deterred from feeding. This sex
      specificity of the moulting hormone, in combination with the female sex
      pheromone, which has no anti-feeding properties, ensures that male crabs mate
      with soft-shelled, moulted females rather than engage in cannibalism, such as
      found frequently in cases when soft-shelled females are exposed to intermoult
      females.

PMID- 17540369
TI  - Increased chondroitin sulfate proteoglycan expression in denervated brainstem
      targets following spinal cord injury creates a barrier to axonal regeneration
      overcome by chondroitinase ABC and neurotrophin-3.
AB  - Increased chondroitin sulfate proteoglycan (CSPG) expression in the vicinity of a
      spinal cord injury (SCI) is a primary participant in axonal regeneration failure.
      However, the presence of similar increases of CSPG expression in denervated
      synaptic targets well away from the primary lesion and the subsequent impact on
      regenerating axons attempting to approach deafferented neurons have not been
      studied. Constitutively expressed CSPGs within the extracellular matrix and
      perineuronal nets of the adult rat dorsal column nuclei (DCN) were characterized
      using real-time PCR, Western blot analysis and immunohistochemistry. We show for
      the first time that by 2 days and through 3 weeks following SCI, the levels of
      NG2, neurocan and brevican associated with reactive glia throughout the DCN were
      dramatically increased throughout the DCN despite being well beyond areas of
      trauma-induced blood brain barrier breakdown. Importantly, regenerating axons
      from adult sensory neurons microtransplanted 2 weeks following SCI between the
      injury site and the DCN were able to regenerate rapidly within white matter (as
      shown previously by Davies et al. [Davies, S.J., Goucher, D.R., Doller, C.,
      Silver, J., 1999. Robust regeneration of adult sensory axons in degenerating
      white matter of the adult rat spinal cord. J. Neurosci. 19, 5810-5822]) but were
      unable to enter the denervated DCN. Application of chondroitinase ABC or
      neurotrophin-3-expressing lentivirus in the DCN partially overcame this
      inhibition. When the treatments were combined, entrance by regenerating axons
      into the DCN was significantly augmented. These results demonstrate both an
      additional challenge and potential treatment strategy for successful functional
      pathway reconstruction after SCI.

PMID- 17540371
TI  - CRF type 1 receptors in the dorsal periaqueductal gray modulate anxiety-induced
      defensive behaviors.
AB  - The dorsal periaqueductal gray (dPAG) is involved in defensive coping reactions
      to threatening stimuli. Corticotropin releasing factor (CRF) is substantially
      implicated as a direct modulator of physiological, endocrine and behavioral
      responses to a stressor. Previous findings demonstrate a direct role of the
      central CRF system in dPAG-mediated defensive reactions toward a threatening
      stimulus. These include anxiogenic behaviors in the elevated plus maze (EPM) in
      rats and defensive reactions in both the mouse defense test battery (MDTB) and
      rat exposure test (RET) paradigms in mice. Furthermore, CRF was shown to directly
      and dose-dependently excite PAG neurons in vitro. The aim of the present series
      of experiments was to directly evaluate the role of the CRF1 receptor (CRF1) in
      dPAG-induced defensive behaviors in the MDTB and the RET paradigms. For this
      purpose, cortagine, a novel CRF1-selective agonist, was directly infused into the
      dPAG. In the RET the high dose of cortagine (100 ng) significantly affected
      spatial avoidance measures and robustly increased burying behavior, an
      established avoidance activity, while having no effects on behaviors in the MDTB.
      Collectively, these results implicate CRF1 in the dPAG as a mediator of
      temporally and spatially dependent avoidance in response to controllable and
      constant stimuli.

PMID- 17540372
TI  - Bleeding retroperitoneal sarcoma after blunt abdominal trauma.

PMID- 17540373
TI  - Basal skull fractures delay coagulation.

PMID- 17540374
TI  - Intramedullary nailing for non-union of the humeral diaphysis: a review.

PMID- 17540375
TI  - Decreased navigated drilling time using an external guide stabilising device.
AB  - INTRODUCTION: Computer navigation in orthopaedic procedures can improve accuracy
      and decrease radiation time compared to traditional fluoroscopy. Many different
      applications are now available, and drilling is commonly used amongst them. Aside
      from additional set up time required, the drilling procedure itself may take a
      significant amount of time. We hypothesised that using an external stabilising
      guide which can be set anywhere in space can decrease then time necessary for
      navigated drilling. METHODS: Foam blocks, 80 mm in length and a density similar
      to cancellous bone, were obtained. Small discs were placed on one end as drilling
      targets. Using an Iso-C 3D navigation system, 20 navigated drilling trials were
      performed under each of two conditions: freehand, and with the use of a drill
      stabilising guide attached to an operating table. The time and accuracy of the
      two methods were compared. RESULTS: The time required for the entire navigation
      procedure was significantly less using the stabilising arm compared to drilling
      freehand with navigation (4.5 min versus 5.8 min, p=0.009). There was no
      significant difference in accuracy between the two methods. CONCLUSION: Using a
      guide which attaches to the table and allows the surgeon to fix the drill sleeve
      when the desired vector is chosen allows for faster navigated drilling. This was
      easy to set up and attach to the table, and did not diminish accuracy of drilling
      an intended target.

PMID- 17540376
TI  - Sliding trochanteric osteotomy in acetabular fractures: a review of 30 cases.
AB  - OBJECTIVE: To assess the results of using sliding trochanteric osteotomy as an
      adjunct procedure for acetabular fractures. DESIGN: Retrospective review.
      SETTING: Level 1 trauma centre. METHODS: Thirty patients (19 men, 11 women, mean
      age 40 years, range 23-80 years) having fracture of acetabulum underwent sliding
      trochanteric osteotomy for a better exposure of the fracture involving the dome
      of acetabulum during the period January 1999-January 2004. MAIN OUTCOME
      MEASUREMENTS: Clinical evaluation was based on modified Merle d' Aubigne and
      Postel scoring. Motor strength of the abductors was evaluated according to the
      Medical Research Council (MRC) grading system. Radiographic evaluation of the
      joint was also documented. RESULTS: All the osteotomies healed within 12 weeks
      without any proximal migration except for one patient with infection in whom
      nonunion occurred. Two patients underwent removal of implants from greater
      trochanter because of irritation. The strength of the abductors was of Grade 2/5
      in one patient, Grade 3/5 in one patient, Grade 4/5 in six patients and Grade 5/5
      in the rest. Clinical scoring was excellent to good in 77%. Heterotopic
      ossification occurred in six patients and was of modified Brooker's classes 1 and
      2. CONCLUSIONS: This technique can be relied upon to provide an adequate exposure
      of the dome of acetabulum without the associated complications like malunion, non
      union, etc., known to occur with standard oblique osteotomy.

PMID- 17540377
TI  - Anterior or posterior obliquity of the lag screw in the lateral view--does it
      affect the sliding characteristics on unstable trochanteric fractures?
AB  - We investigated the sliding pattern characteristics of proximal fragment in 16
      proximal femur models of 31-A2.1 type trochanteric fractures fixed with dynamic
      hip screw system under load. In eight models, the lag screw was inserted with an
      anterior-to-posterior vector within the neck and the head of femur (group 1). The
      other eight had a posterior-to-anterior vector (group 2). A force of 500 N (30
      cycles) was applied to the fracture fragment-plate complex using the Instron
      6022. No significant difference was noted in the sliding distance between the two
      groups (p=0.17). However, the mean angle of rotation of the proximal fragment was
      twice as great in group 1 (16+/-3.7 degrees ) than that in group 2 (8.1+/-1.5
      degrees ) (p<0.001). In group 1, early eccentric contact in the anterior aspect
      of the intertrochanteric area caused internal rotation of the proximal fragment.
      Breakage of the anterior cortex of the lateral wall was noted in five out of the
      eight cases in group 1 and no case in group 2 (p=0.026). Fracture of the anterior
      cortices significantly threatened the integrity of the lateral wall in group 1.

PMID- 17540378
TI  - Estimating femoral nail length in bilateral comminuted fractures using fibular
      and femoral head referencing.
AB  - OBJECTIVE: Femoral nail length can be estimated preoperatively by several
      methods, but this usually requires an intact contralateral femur. The aim of this
      study was to determine an alternative method using fibula and femoral head as
      references. MATERIALS AND METHODS: Digital radiographic views of the lower limbs
      of 102 healthy volunteers were used to compare femoral medullary length with the
      sum of fibular length and transverse head diameter. RESULTS: Femoral medullary
      length and the estimated length were highly correlated (r=0.942, p<0.0001).
      Paired samples t-testing has produced a high significance (p<0.002). CONCLUSION:
      The formula provides a simple and accurate estimation of femoral medullary
      length, and may be used in nailing, particularly of bilateral comminuted femoral
      fractures.

PMID- 17540379
TI  - Old people receiving municipal care, their experiences of what constitutes a good
      life in the last phase of life: a qualitative study.
AB  - BACKGROUND: Old people's life situation when receiving municipal help and care in
      their last period of life is sparsely investigated from their own perspective.
      OBJECTIVE: The aim of this study was to investigate the experiences of aspects
      that bring about a good life in the last phase of life among people (75+ years)
      receiving municipal care. PARTICIPANTS: Older people living in a municipality in
      Southern Sweden being 75 years or older, receiving help and/or care from the
      municipality, and having a life-threatening disease and/or receiving palliative
      care were asked to participate. In all 17 people, 10 women and 7 men, aged 78-100
      years were included. METHODS: Qualitative interviews, with the emphasis on their
      present life situation especially what brought about a good life, were performed.
      The interviews were analysed using qualitative content analysis. RESULTS: The
      experience was interpreted to be Turning inwards to come to peace with the past,
      the present and approaching death while being trapped by health complaints. Six
      categories embraced the experience of aspects that constitute a good life in the
      last phase of life: Maintaining dignity, Enjoying small things, Feelings of
      "being at home", Being in the hands of others, trying to adjust, Still being
      important for other people and Completing life while facing death. CONCLUSION:
      This study confirm theories suggesting that the last phase of life in old age
      meant focusing inwards, reflecting on the entire life as a way of completing it
      as well as enjoying small things and also viewing oneself in the perspective of
      contributing to the future. It also indicated that this phase of life meant being
      trapped by health complaints and functional limitations. The struggle to
      maintaining dignity as opposed to being in the hands of others implies that the
      concept of palliative care may be useful as a framework for providing nursing
      care to very old people, especially at the end of life.

PMID- 17540380
TI  - The secondary structure of the unusually long 18S ribosomal RNA of the myxozoan
      Sphaerospora truttae and structural evolutionary trends in the Myxozoa.
AB  - The nearly complete 18S rRNA sequence of the myxozoan parasite Sphaerospora
      truttae shows an extraordinary length (2,552bp) in comparison with other
      myxozoans and with metazoans in general (average 1,800-1,900bp). The sequence
      shows nucleotide insertions in most variable regions of the 18S rRNA (V2, V4, V5
      and V7), with especially large expansion segments in V4 and V7. In the myxozoans,
      nucleotide insertions and specific secondary structures in these regions of the
      gene were found to be strongly related to large scale phylogenetic clustering and
      thus with the invertebrate host type. Whereas expansion segments were generally
      found to be absent in the malacasporeans and the clade of primary marine myxozoan
      species, they occur in all taxa of the clade containing freshwater species, where
      they showed a consistent secondary structure throughout. The longest expansion
      segments occur in S. truttae, Sphaerospora elegans and Leptotheca ranae, which
      represent a clade that has emerged after the malacosporeans and before the
      radiation of all other myxozoan genera. These three species demonstrate
      structural links to the malacosporeans as well as other unique features. A
      smaller number of nucleotide insertions in different subhelices and specific
      secondary structures appear to have evolved independently in two marine genera,
      i.e. Ceratomyxa and Parvicapsula. The secondary structural elements of V4 and V7
      of the myxozoan 18S rRNAs were found to be highly informative and revealed
      evolutionary trends of various regions of the gene hitherto unknown, since
      previous analyses have been based on primary sequence data excluding these
      regions. Furthermore, the unique features of the V4 region in S. truttae allowed
      for the design of a highly specific PCR assay for this species.

PMID- 17540382
TI  - Elevated serum soluble endoglin (sCD105) decreased during extracorporeal
      elimination therapy for familial hypercholesterolemia.
AB  - Extracorporeal elimination is a method of LDL-lowering therapy that is used in
      severe familial hypercholesterolemia (FH) after other therapeutic approaches have
      failed. There are currently no universally accepted biomarkers that would allow
      determining necessary intensity of therapy and frequency of future therapeutic
      interventions. An ideal tool for immediate evaluation would be a readily
      measurable serum marker. We hypothesized that soluble endoglin (sCD105), a
      recently described indicator of endothelial dysfunction, may represent such a
      tool. Eleven patients with FH (three homozygous, eight heterozygous; Fredrickson
      type IIa, IIb) that have been monitored for 4.5+/-2.8 years were treated; eight
      by LDL-apheresis and three by hemorheopheresis. 40 sCD105 measurements were done,
      before and after two consecutive elimination procedures. Baseline serum sCD105
      levels were significantly higher in the patients (5.74+/-1.47 microg/l in series
      I, 6.85+/-1.85 microg/l in series II) than in the control group (3.85+/-1.25
      microg/l). They decreased to normal after LDL-elimination (p=0.0003) in all
      except for one patient. This return to normal was not due to a non-specific
      capture of endoglin in adsorption or filtration columns as demonstrated by
      measurement of sCD105 before and after passage through the elimination media. We
      conclude that the soluble endoglin levels in patients with severe FH remain
      elevated despite long-term intensive therapy and that they decrease after
      extracorporeal elimination. Endoglin can therefore serve as a marker for
      evaluation of the treatment efficacy and of the decreased atherosclerotic
      activity in patients with FH treated by extracorporeal LDL-cholesterol
      elimination.

PMID- 17540383
TI  - A novel hollow-fibre microporous membrane liquid-liquid extraction for
      determination of free 4-isobutylacetophenone concentration at ultra trace level
      in environmental aqueous samples.
AB  - In this study, a method was developed for determination of the free concentration
      of 4-isobutylacetophenone, a toxic degradation product of ibuprofen, in river and
      sewage water samples from Sweden. Sample preparation and analysis were performed
      by a hollow-fibre microporous membrane liquid-liquid extraction (HF-MMLLE) set-up
      and gas chromatography-mass spectrometry (GC-MS), respectively. In this novel
      approach, only the liquid in the membrane pores is utilised for non-depleting
      extraction. Several parameters were studied, including: type of organic solvent,
      sample pH, and salt and humic acid content. The optimised method allowed the
      determination of the analyte at the ng L(-1) level in river and sewage water. A
      linear plot gave a correlation coefficient better than 0.992 and resulted in a
      limit of detection of 7 and 14 ng L(-1) for river and sewage water, respectively.
      The enrichment factor was over 2000 in the fibre and over 300 after dilution. The
      repeatability and reproducibility were better than 5% and 10%, respectively. For
      the first time, 4-isobutylacetophenone was found at free concentrations of 40 ng
      L(-1) or below in sewage waters, while it could not be quantified in a river
      downstream from a municipal sewage treatment plant.

PMID- 17540384
TI  - Analytical method for the determination of sterigmatocystin in grains using high
      performance liquid chromatography-tandem mass spectrometry with electrospray
      positive ionization.
AB  - A sensitive LC-electrospray positive ionization (ESI+) MS/MS method was developed
      and validated for the determination of the Aspergillus mycotoxin,
      sterigmatocystin, in grains at levels down to less than 0.5 microg/kg. Recovery
      was found to be greater than 97% for wheat grains.

PMID- 17540385
TI  - Amino acid profiling in urine by capillary zone electrophoresis - mass
      spectrometry.
AB  - Analysis of amino acid profiles in urine and plasma is an essential part of
      modern clinical diagnostic routine. Here we present an approach for the analysis
      of amino acids in urine by capillary electrophoresis/time-of-flight (TOF) mass
      spectrometry. At first a method combining improved separation, high dynamic
      range, and high sensitivity is presented. Detection limits in the mid nM-range
      are achieved through the use of pH-mediated stacking injection in combination
      with modern TOF detection technology. The method can be easily applied to detect
      differences in the amino acid profile in urine in a clinical context. Moreover,
      beside amino acids low molecular weight amines, peptides and related metabolites
      can be profiled. As a proof of concept, urine samples from patients suffering
      from osteoarthritis have been analyzed. Finally, the introduction of multivariate
      data analysis in the work flow was evaluated on spiked urine samples and real
      clinical material.

PMID- 17540386
TI  - Simultaneous determination of nine intense sweeteners in foodstuffs by high
      performance liquid chromatography and evaporative light scattering detection-
      development and single-laboratory validation.
AB  - A high performance liquid chromatographic method with evaporative light
      scattering detection (HPLC-ELSD) has been developed for the simultaneous
      determination of multiple sweeteners, i.e., acesulfame-K, alitame, aspartame,
      cyclamic acid, dulcin, neotame, neohesperidine dihydrochalcone, saccharin and
      sucralose in carbonated and non-carbonated soft drinks, canned or bottled fruits
      and yoghurt. The procedure involves an extraction of the nine sweeteners with a
      buffer solution, sample clean-up using solid-phase extraction cartridges followed
      by an HPLC-ELSD analysis. The trueness of the method was satisfactory with
      recoveries ranging from 93 to 109% for concentration levels around the maximum
      usable dosages for authorised sweeteners and from 100 to 112% for unauthorised
      compounds at concentration levels close to the limit of quantification (LOQs).
      Precision measures showed mean repeatability values of <4% (expressed as relative
      standard deviation) for highly concentrated samples and <5% at concentration
      levels close to the LOQs. Intermediate precision was in most cases <8%. The
      limits of detection (LODs) were below 15 microg g(-1) and the LOQs below 30
      microg g(-1) in all three matrices. Only dulcin showed slightly higher values,
      i.e., LODs around 30 microg g(-1) and LOQs around 50 microg g(-1)

PMID- 17540387
TI  - Column temperature as an active variable in the isocratic, normal-phase high
      performance liquid chromatography separation of lipophilic metabolites of
      nonylphenol ethoxylates.
AB  - Normal-phase separation of technical grade nonylphenol (t-NP, about 90% 4
      nonylphenol), 4-nonylphenol mono-ethoxylate (4-NP1EO) and 4-nonylphenol di
      ethoxylate (4-NP2EO) was assessed, with the inclusion of column temperature as an
      active variable. The compound 2,4,6-trimethylphenol was evaluated for use as
      internal standard. Isocratic elution with 2-propanol/hexanes mixtures from an
      amino-silica column and spectrometric UV detection at 277 nm were employed.
      Technical nonylphenol presented a significant contribution from unknown
      substances that eluted with retention times similar to that of 4-NP1EO. GC-MS
      analysis of the unknowns allowed to identify them as isomers of 2-NP. The
      response of the system to joint variations in flow rate, eluent composition and
      column temperature was investigated by means of Doehlert statistical experimental
      design. A model for retention of the analytes as a function of the experimental
      variables was proposed, and separation selectivity was studied. Selection of the
      optimal working zone was made through desirability function (D) calculations.
      Potential co-elution of 2-NP isomers with 4-NP1EO was considered when optimizing
      the separation. The occurrence of a restricted region of the experimental space
      where baseline resolution of analytes, associated impurities and internal
      standard results feasible (D not equal to 0) is apparent.

PMID- 17540388
TI  - Proceedings of the 30th International Symposium on High Performance Liquid Phase
      Separations and Related Techniques. June 17-23, 2006. San Francisco, California,
      USA.

PMID- 17540389
TI  - Application of pressurized fluid extraction technique in the gas chromatography
      mass spectrometry determination of sterols from marine sediment samples.
AB  - In order to determine steroid compounds in GC/MS an analytical method using
      pressurized fluid extraction (PFE) was developed. While extracting in-house
      reference material (coastal sediment) typical recovery in PFE ranged from 80 to
      120% (+/-2.5-14.5) and the average extraction yield in PFE in comparison to
      conventional soxhlet extraction was 115%. In particular, the PFE showed higher
      extraction efficiency for C29 and dien sterols. Optimizing parameters such as
      temperature and pressure is critical in achieving this efficiency. Sterols in the
      sediment were derivatized with silyl reagent BSTFA in acetone for the final
      determination. A short column florisil cleanup offered the best separation of the
      GC/MS sensitive derivatives from co-contaminants. Thirty-three coastal sediment
      samples were analyzed using PFE and Soxhlet extraction methods. The results on
      extraction efficiency, silyl derivatization kinetics and purification efficiency
      demonstrated that PFE is far superior in extracting sterols from sediment
      samples. It is simple, fast, efficient and amenable for automation.

PMID- 17540390
TI  - Influence of the methacrylate monolith structure on genomic DNA mechanical
      degradation, enzymes activity and clogging.
AB  - The chromatography of mechanically sensitive macromolecules still represents a
      challenge. While larger pores can reduce the mechanically induced cleavage of
      large macromolecules and column clogging, the column performance inevitably
      decreases. To investigate the effect of pore size on the mechanical degradation
      of DNA, column permeability and enzyme biological activity, methacrylate
      monoliths with different pore sizes were tested. Monolith with a 143 nm pore
      radius mechanically damaged the DNA and was clogged at flow rates above 0.5 ml
      min(-1) (26 cm h(-1)). For monoliths with a pore radius of 634 nm and 2900 nm, no
      mechanical degradation of DNA was observed up to 5 ml min(-1) (265 cm h(-1))
      above which the HPLC itself became the main source of damage. A decrease of a
      permeability appeared at flow rate 1.8 ml min(-1) (95 cm h(-1)) and 2.3 ml min(
      1) (122 cm h(-1)), respectively. The effect of the pore size on enzyme biological
      activity was tested with immobilized DNase and trypsin on all three monoliths.
      Although the highest amount of enzyme was immobilized on the monolith with the
      smallest pores, monolith with the pore radius 634 nm exhibited the highest DNase
      biological activity probably due to restricted access for DNA molecules into the
      small pores. Interestingly, specific biological activity was increasing with a
      pore size decrease. This was attributed to higher number of contacts between a
      substrate and immobilized ligand.

PMID- 17540391
TI  - High-performance liquid chromatography and non-destructive three-dimensional
      fluorescence analysis of early synthetic dyes.
AB  - Chromatographic and spectroscopic techniques are evaluated for the analysis of
      early synthetic dyes. The research focuses on the analysis of dyestuffs that were
      developed and used in the period 1850-1900, which has not been well investigated
      so far. The aim of this study was to develop and evaluate techniques that can be
      applied in the field of culture and art. A selection of 65 synthetic dyestuffs
      was chosen to investigate the usefulness of the analytical techniques applied. As
      a case study three embroideries, designed by the well-known 19th century French
      painter Emile Bernard, were investigated to obtain more information about the use
      and behaviour of synthetic dyes.

PMID- 17540392
TI  - Supervised pattern recognition in food analysis.
AB  - Data analysis has become a fundamental task in analytical chemistry due to the
      great quantity of analytical information provided by modern analytical
      instruments. Supervised pattern recognition aims to establish a classification
      model based on experimental data in order to assign unknown samples to a
      previously defined sample class based on its pattern of measured features. The
      basis of the supervised pattern recognition techniques mostly used in food
      analysis are reviewed, making special emphasis on the practical requirements of
      the measured data and discussing common misconceptions and errors that might
      arise. Applications of supervised pattern recognition in the field of food
      chemistry appearing in bibliography in the last two years are also reviewed.

PMID- 17540393
TI  - Comparative study of an estradiol enzyme-linked immunosorbent assay kit, liquid
      chromatography-tandem mass spectrometry, and ultra performance liquid
      chromatography-quadrupole time of flight mass spectrometry for part-per-trillion
      analysis of estrogens in water samples.
AB  - Estrogens have been often identified as the major contributors to the endocrine
      disrupting activity observed in environmental waters. However, their analysis in
      these, sometimes very complex, matrices is still challenging due to the very low
      detection limits and the selectivity required for their reliable determination at
      the very low concentrations at which they are physiologically active. In this
      work, a polyclonal enzyme-linked immunosorbent assay (ELISA) kit for 17-beta
      estradiol analysis, high-performance liquid chromatography-tandem mass
      spectrometry (HPLC-MS/MS) based on triple-quadrupole analyzer (QqQ), and a newly
      developed method based on ultra performance liquid chromatography-quadrupole time
      of flight mass spectrometry (UPLC-Q-TOF-MS) have been evaluated in terms of
      performance for the rapid screening, quantitative analysis, and unequivocal
      identification of some selected, environmentally relevant estrogens in different
      water matrices, including urban wastewater, river water, and ground water, after
      solid phase extraction. Compounds quantified and/or identified included the
      estrogens 17-beta-estradiol, estrone, 17-alpha-ethynyl estradiol and estriol, and
      the isoflavones daidzein, genistein, and biochanin A. Except for a moderate
      overestimation using the ELISA kit, especially in the analysis of complex
      wastewater samples, results obtained by all the investigated techniques were in
      very good, general agreement. The instrumental sensitivity achieved increased in
      the order: UPLC-Q-TOF-MS < polyclonal ELISA kit < HPLC-MS/MS (QqQ). Direct
      analysis of water samples by using the ELISA kit permitted to reach a limit of
      detection of 2.5 ng L(-1). However, using an appropriated sample pretreatment
      method detection limits at nanogram to picogram per liter levels can be obtained
      with all techniques and the risk for matrix effects is minimized. In terms of
      selectivity, both HPLC-MS/MS (QqQ) and UPLC-Q-TOF-MS show outstanding
      performance, but the latter allows, in addition, shorter analysis times (16 min
      vs. 45 min) and the identification of non-target, unknown compounds. The
      identification of unknown compounds is based on the accurate mass measurements
      for the precursor and product ions, that permit the elemental compositions
      calculation and the chemical structures to be identified searching against
      different databases.

PMID- 17540394
TI  - Dielectric analysis of the APG/n-butanol/cyclohexane/water nonionic
      microemulsions.
AB  - The nonionic APG/n-butanol/cyclohexane/water microemulsions with different
      microstructure, which is induced by the variation of water contents, are
      investigated by the dielectric spectroscopy. An appropriate dielectric theory,
      Hanai theory and the corresponding analytical method are applied to obtain the
      internal properties of the constituent phases of microemulsions, such as the
      relative permittivity and conductivity of continuous and dispersed phases and the
      volume fraction of dispersed phase. Using these parameters, the distribution of n
      butanol in constituent phases, which is of important in the study field of the
      microstructure of microemulsion, is obtained quantitatively. It is found that the
      n-butanol molecules not only distribute in the interfacial APG layer but also in
      the continuous and dispersed phases. In addition, the percolation threshold is
      interpreted by using the dynamic percolation model. The structural and dynamic
      information are obtained, for instance, the critical volume fraction of water
      when percolation occurs and the characteristic time for the rearrangement of
      clusters. These parameters are intimately related to the properties of
      microemulsions, especially the characteristics of the interfacial layer.

PMID- 17540395
TI  - The emulsion flocculation stability of protein-carbohydrate diblock copolymers.
AB  - The effect of the steric layer thickness on the flocculation stability of beta
      lactoglobulin-carbohydrate diblock copolymers was assessed. The diblock
      copolymers were created by conjugating beta-lactoglobulin to maltose or a series
      of different M(n) maltodextrins using the Maillard reaction. The thickness and
      spatial arrangement of the interfacial layers were assessed via latex adsorption
      and selective enzymatic digestion studies. An increase in the molecular weight of
      the maltodextrin (900, 1900 and 3800 Da) increased the interfacial thickness
      (1.1, 2.5 and 7.3 nm, respectively). No detectable change to interfacial
      thickness was observed upon the attachment of maltose. The increase in the
      interfacial layer thickness scaled with the hydrodynamic size of the
      carbohydrate. The beta-lactoglobulin-maltodextrin conjugates were found to have a
      diblock architecture, with the protein anchored at the surface and the
      carbohydrate protruding into the aqueous continuous phase. The stability of oil
      in-water emulsions formed using the conjugates was assessed by exposing them to
      salt (150 mM NaCl or 0-20 mM CaCl(2)), heat alone or heat in the presence of 150
      mM NaCl. Conjugation of a 900 Da maltodextrin provided sufficient steric
      stabilization to prevent flocculation in high salt environments. The effect of
      the (number) density of the steric layer was also assessed by controlling the
      average number of maltodextrins attached per beta-lactoglobulin molecule. The
      steric layer density at which emulsions became unstable was a function of
      carbohydrate M(n). Emulsions made from the 900 Da maltodextrin conjugate became
      unstable below a steric layer density of one tail per 7.5 nm(2), whilst emulsions
      made from the 1900 Da maltodextrin were unstable below a steric layer density of
      one tail per 9.5 nm(2). This trend was expected and can be explained by the
      stronger van der Waals attraction that arises from the closer interdroplet
      separations that are permissible with the shorter maltodextrins. The excellent
      flocculation stability of Maillard conjugate emulsions is thought to arise from
      the combined effects of weak electrostatic repulsion from the screened protein
      surface charge and steric repulsion from the attached carbohydrate layer. This
      means that attachment of a relatively thin steric layer is enough to stabilize
      the emulsions against flocculation. These findings have important implications
      for the development of commercial processes to manufacture protein-carbohydrate
      Maillard conjugate emulsifiers. Furthermore the work provides a greater empirical
      understanding of the relationship between interfacial architecture and colloidal
      stability, and may provide the means for greater theoretical understanding of
      biopolymer stabilization of interfaces.

PMID- 17540396
TI  - Mixed Langmuir monolayers of gramicidin A and fluorinated alcohols.
AB  - Mixed monolayers of gramicidin A (GA) and three alcohols, differing in the degree
      of fluorination, namely C18OH, F18OH, and F8H10OH have been investigated by means
      of: surface manometry (pi-A isotherms) and Brewster angle microscopy (BAM) aiming
      at finding appropriate molecules for incorporating gramicidin A for a biosensor
      design. Our results proved that only the semifluorinated alcohol is appropriate
      material for this purpose since it forms miscible and homogeneous monolayers with
      GA within the whole concentration range. The experimental results have been
      supported by the calculations of van der Waals energy profiles using the Insight
      II program. Both the hydrogenated and perfluorinated alcohols were found to
      aggregate at higher surface pressures, which exclude their application for
      gramicidin-based biosensor construction.

PMID- 17540397
TI  - Biomolecule induced nanoparticle aggregation: effect of particle size on
      interparticle coupling.
AB  - Gold nanoparticles of variable sizes have been prepared by reducing HAuCl(4) with
      trisodium citrate by Frens' method. It has been found that the gold particles
      under consideration produce well-ordered aggregates upon interaction with a
      biomolecule, glutathione in variable acidic pH condition and exhibit pronounced
      changes in their optical properties arising due to electromagnetic interaction in
      the close-packed assembly. The effect of nanoparticle size on the nature of
      aggregation as well as the variation in the optical response due to variable
      degree of interparticle coupling effects amongst the gold particles have been
      investigated. The optical properties of the gold aggregates have been accounted
      in the light of Maxwell-Garnett effective medium theory considering the changes
      in the filling factor in different aggregates produced by variable sizes of gold
      colloids. The aggregates have been characterized by UV-vis spectroscopy, FTIR,
      Raman, XRD and TEM studies. It has been observed that a new peak appearing at a
      longer wavelength intensifies and shifts further to the red from the original
      peak position depends on the particle size, concentration of glutathione and pH
      of the solution. On the basis of the first appearance of a clearly defined new
      peak at longer wavelength, a higher sensitivity of glutathione detection has been
      achieved with gold nanoparticles of larger dimension.

PMID- 17540398
TI  - Viscoelastic behavior of surfactants worm-like micellar solution in the presence
      of alkanolamide.
AB  - A study of the phase and rheological behavior of anionic surfactant sodium
      dodecyl trioxyethylene sulfate (SDES) and nonionic polyoxyethylene sorbitan
      monooleate (Tween-80) with alkanoyl-N-methylethanolamide (C(12), NMEA-12; and
      C(16), NMEA-16) in aqueous system is presented. Upon addition of NMEA to the semi
      dilute solution of SDES or Tween-80, induces micellar growth leading to the
      formation of a gel-like highly viscoelastic solution in the maximum viscosity
      region. These solutions obey the Maxwell model of a viscoelastic fluid. It was
      observed from rheological measurements that NMEA-16 is more effective than NMEA
      12 to induce the micellar growth of surfactants. The relationship between the
      marked changes in viscosity with surfactant-cosurfactant mixing ratio based on
      the experimental observations is discussed.

PMID- 17540399
TI  - Size-controlled gold nanocolloids on polymer microsphere-stabilizer via
      interaction between functional groups and gold nanocolloids.
AB  - Gold nanocolloids with the controlled diameter ranging from 5.2 to 10.7 nm were
      in situ prepared by reduction of gold chloride trihydrate with sodium borohydride
      as reductant via the interaction between the gold naocolloids and the functional
      groups on the surface of polymer microsphere-stabilizer. The nature of such
      interaction was studied in detail by X-ray photoelectron spectroscopy (XPS). The
      effect of the functional groups on the catalytic activity of the gold
      nanocolloids was preliminarily investigated with the reduction of 4-nitrophenol
      to 4-aminophenol in the presence of sodium borohydride as reductant.

PMID- 17540400
TI  - Development of a modified microtiter plate with a concave portion in the center.
AB  - We have developed a modified microtiter plate which has following advantageous
      features and functions to both conventional microtiter plate and protein array,
      such as 1) use of conventional microtiter plate reader and washer, and 2)
      allowance of simultaneous reaction in the same liquid for all wells. Four
      proteins of human serum albumin, human C-reactive protein (CRP), human
      plasminogen and human MIP-1alpha as sample proteins, were measured with the
      modified microtiter plate. Although the reaction liquid of each wells on the
      modified microtiter plate shares through concave portion, its antigen/antibody in
      each well is independent. The independence of the reaction is supported by the
      result that the above four proteins produced dose-response curves simultaneously.
      Unlike a conventional protein array, our plate does not need the drying process
      for antibody adhesion to the plate, preventing inactivation of the antibody. And
      one can detect the antigen/antibody reaction using the enzymatic amplification
      reaction (for example utilizing the biotin-streptavidine interaction) like a
      conventional plate. In addition to these features, our microtiter plate also has
      the merit of eliminating the so-called "edge effect".

PMID- 17540401
TI  - A multimarker real-time RT-PCR for MAGE-A gene expression allows sensitive
      detection and quantification of the minimal systemic tumor load in patients with
      localized cancer.
AB  - INTRODUCTION: Distant metastases of solid tumors are usually associated with
      fatal outcome. Disseminated cancer cells are considered early indicators of
      metastasis. Their sensitive detection and quantification would be a valuable tool
      for staging of disease and as guidance for therapeutic decisions. EXPERIMENTAL
      DESIGN: We established a highly sensitive and quantitative multimarker real-time
      RT-PCR assay for amplification of cancer-related genes MAGE-A1, -A2, -A3/6, -A4, 
      A10 and -A12 using SYBR green I to detect one single tumor cell in 2 mL of blood
      or bone marrow. The feasibility of the assay was tested in a large cohort of 177
      patients with locally confined prostate carcinoma. RESULTS: Analysis revealed
      frequent MAGE expression in venous blood and bilateral bone marrow samples (25.5%
      of all cases) and yielded the first quantitative profile of MAGE expression with
      a broad range of transcript concentrations for individual markers in the minimal
      systemic tumor load of patients with localized cancer. CONCLUSIONS: Rare
      transcripts of different MAGE-A genes can be quantified in clinical samples of
      cancer patients by a sensitive multimarker real-time RT-PCR. Because of frequent
      expression of MAGE genes in various types of cancer the multimarker MAGE real
      time RT-PCR may be generally useful for detection, quantification and
      characterization of the individual disseminated tumor load in cancer patients.

PMID- 17540402
TI  - Anti-predator defence mechanisms in sawfly larvae of Arge (Hymenoptera, Argidae).
AB  - Larvae of the sawfly Arge (Hymenoptera, Argidae) are exposed to predators such as
      ants. Their defence mechanisms, which have been almost unstudied, were
      investigated by behavioural observations coupled to a morphological approach and
      by testing the bioactivity of several body parts. Arge larvae raised their
      abdomen when contacted by Myrmica rubra workers. The ants rarely bit a larva and
      generally retreated immediately, sometimes without contacting it. Most of those
      few ants that bit a larva then showed an uncoordinated walk. Crude hemolymph from
      a common species, A. pagana, was a feeding deterrent towards ants. Hemolymph
      extracts remained active up to a concentration of 0.8 microg DW extract per
      microlitre solution, and were more active than integument and gut extracts. We
      also observed ants paralysed by extracts, especially from the gut. It is likely
      that this toxicity is due to a polypeptide, lophyrotomin, which is known to occur
      in A. pullata. Six or seven non-eversible ventro-abdominal glands occurred in all
      species studied (A. fuscipes, A. nigripes, A. ochropus, A. pagana, A. pullata, A.
      ustulata). These glands contain volatiles. We consider both types of chemicals to
      be important in defence, and we propose that the paralysing effect is a common
      feature among Arge species.

PMID- 17540403
TI  - Carbacyclin induces carnitine palmitoyltransferase-1 in cardiomyocytes via
      peroxisome proliferator-activated receptor (PPAR) delta independent of the IP
      receptor signaling pathway.
AB  - Prostacyclin (PGI2) and its analogues exert cardioprotective effects via the
      rhodopsin type membrane PGI2 receptor, IP. Peroxisome proliferator-activated
      receptor (PPAR) delta is a nuclear receptor abundantly expressed in
      cardiomyocytes and plays a pivotal role in maintaining constitutive mitochondrial
      fatty acid beta-oxidation (FAO). Recently, a novel signaling pathway of PGI2 via
      PPARdelta has been demonstrated in non-cardiac tissues. We therefore examined
      whether carbacyclin (cPGI2), a PGI2 analogue, up-regulates transcriptional
      expression of carnitine palmitoyltransferase-1 (CPT-1), the rate-limiting enzyme
      in mitochondrial FAO, via PPARdelta in cardiomyocytes. Intraperitoneal injection
      of cPGI2 increased CPT-1 mRNA expression in murine hearts. Transcriptional
      activity was evaluated by PPAR responsive element (PPRE)-luciferase reporter gene
      assay in cultured neonatal rat cardiomyocytes. CPT-1 mRNA expression and PPRE
      promoter activity were significantly increased by cPGI2 in a concentration
      dependent manner, where PPRE has been mapped to the promoter region of the CPT-1
      gene. Moreover, the elevation of CPT-1 mRNA expression and PPRE promoter activity
      by cPGI2 was not abolished by H-89, a potent protein kinase A inhibitor, but was
      significantly inhibited in cardiomyocytes over-expressing a dominant-negative
      type of PPARdelta. Furthermore, electrophoretic mobility shift assays
      demonstrated that binding of PPARdelta to PPRE in the CPT-1 gene promoter is
      enhanced in response to cPGI2 stimulation. In addition, down-regulation of CPT-1
      mRNA expression in cardiomyocytes subjected to hypoxia was attenuated by cPGI2.
      These results indicate that cPGI2 induces CPT-1 mRNA expression through
      PPARdelta, independent of the IP receptor signaling pathway, suggesting a
      possibility that cPGI2 modulates cardiac energy metabolism by activating FAO via
      PPARdelta.

PMID- 17540404
TI  - A comparison of adenovirally delivered molecular methods to inhibit Na+/Ca2+
      exchange.
AB  - The ability to use molecular biology tools to down-regulate Na+/Ca2+ exchanger
      (NCX) expression will allow us to better understand the regulation of Ca(i)2+ and
      contractility in heart. Three different techniques to deplete NCX expression were
      compared: short hairpin RNA (shRNA), antisense RNA and exchanger inhibitory
      peptide expression via adenoviral transfection. Our results demonstrate that the
      most efficient method to deplete NCX expression and activity from cardiomyocytes
      is shRNA. It is also possible to replace the endogenous NCX with alternative
      isoforms or mutant forms of the NCX. Adenovirally delivered shRNA is an efficient
      tool for the study of the NCX and could be adapted for many other cardiac
      proteins.

PMID- 17540405
TI  - Uncoating the herpes simplex virus genome.
AB  - Initiation of infection by herpes simplex virus (HSV-1) involves a step in which
      the parental virus capsid docks at a nuclear pore and injects its DNA into the
      nucleus. Once "uncoated" in this way, the virus DNA can be transcribed and
      replicated. In an effort to clarify the mechanism of DNA injection, we examined
      DNA release as it occurs in purified capsids incubated in vitro. DNA ejection was
      observed following two different treatments, trypsin digestion of capsids in
      solution, and heating of capsids after attachment to a solid surface. In both
      cases, electron microscopic analysis revealed that DNA was ejected as a single
      double helix with ejection occurring at one vertex presumed to be the portal. In
      the case of trypsin-treated capsids, DNA release was found to correlate with
      cleavage of a small proportion of the portal protein, UL6, suggesting that UL6
      cleavage may be involved in making the capsid permissive for DNA ejection. In
      capsids bound to a solid surface, DNA ejection was observed only when capsids
      were warmed above 4 degrees C. The proportion of capsids releasing their DNA
      increased as a function of incubation temperature with nearly all capsids
      ejecting their DNA when incubation was at 37 degrees C. The results demonstrate
      heterogeneity among HSV-1 capsids with respect to their sensitivity to heat
      induced DNA ejection. Such heterogeneity may indicate a similar heterogeneity in
      the ease with which capsids are able to deliver DNA to the infected cell nucleus.

PMID- 17540406
TI  - Cyclin box structure of the P-TEFb subunit cyclin T1 derived from a fusion
      complex with EIAV tat.
AB  - The positive transcription elongation factor b (P-TEFb) is an essential regulator
      of viral gene expression during the life cycle of human immunodeficiency virus
      type 1 (HIV-1). Its cyclin T1 subunit forms a ternary complex with the viral
      transcriptional transactivator (Tat) protein and the transactivation response
      (TAR) RNA element thereby activating cyclin dependent kinase 9 (Cdk9), which
      stimulates transcription at the level of chain elongation. We report the
      structure of the cyclin box domain of human cyclin T1 at a resolution of 2.67 A.
      The structure was obtained by crystallographic analysis of a fusion protein
      composed of cyclin T1 linked to the transactivator protein Tat from equine
      infectious anemia virus (EIAV), which is functionally and structurally related to
      HIV-1 Tat. The conserved cyclin box domain of cyclin T1 exhibits structural
      features for interaction with physiological binding partners such as Cdk9. A
      recognition site for Cdk/Cyclin substrates is partly covered by a cyclin T
      specific insert, suggesting specific interactions with regulatory factors. The
      previously identified Tat/TAR recognition motif (TRM) forms a C-terminal helix
      that is partly occluded in the cyclin box repeat interface, while cysteine 261 is
      accessible to form an intermolecular zinc finger with Tat. Residues of the TRM
      contribute to a positively charged groove that may directly attract RNA
      molecules. The EIAV Tat protein instead appeared undefined from the electron
      density map suggesting that it is highly disordered. Functional experiments
      confirmed the TAR binding properties of the fusion protein and suggested residues
      on the second cyclin box repeat to contribute to Tat stimulated transcription.

PMID- 17540408
TI  - Brain perfusion and VEP reactivity in occipital and parietal areas are associated
      to recovery from hypoxic vegetative state.
AB  - Patients in a vegetative state (VS) show a spontaneous wake-sleep-cycle but no
      evidence of awareness, of interaction with the environment, voluntary action, and
      language comprehension. The neuropathological conditions underlying VS are still
      not fully understood. In this retrospective study we focused on VS due to hypoxia
      and used SPECT, VEP and event related potentials (N100, N200, MMN, and P300) to
      assess differences between a group of patients moving into a permanent VS (n=13)
      and a group recovering from VS (n=8). The two groups were matched for age,
      gender, duration of illness, and on the coma remission scale at admission. The
      patient groups differed in global uptake of (99m)Tc-ethylencysteine dimer (being
      reduced in non-recovered VS patients to 2/3 of the recovered group), and in
      presence of VEP and N100 (recovered patients always had a present VEP and N100).
      Moreover, analysis of uptake in specific brain areas showed that the recovered
      group had a higher perfusion in the visual cortex and in the precuneus, whereas
      no differences were found in the frontal pole and more ventral parts of the
      brain. Statistical testing revealed a strong association between occipital and
      parietal perfusion and the presence of a VEP, but no specific results for the
      N100. We conclude that occipital and parietal lobe perfusion and rudimentary
      vision may be critical characteristics distinguishing between VS and patients
      recovered from VS. Although this may just reflect haemodynamics during hypoxia
      leading to differences in severity of VS, it also may be regarded as a functional
      precondition for orientation towards stimuli and therefore for conscious actions
      in general.

PMID- 17540407
TI  - A decrease in N-acetylaspartate and an increase in myoinositol in the anterior
      cingulate gyrus are associated with behavioral and psychological symptoms in
      Alzheimer's disease.
AB  - BACKGROUND AND PURPOSE: The cognitive decline in Alzheimer's disease (AD)
      patients has been reported to involve alterations in the medial temporal lobe and
      the posterior cingulate gyrus. On the other hand, the neurochemical pathologies
      of the behavioral and psychological symptoms of dementia (BPSD) have not been
      sufficiently discussed. The aim of this study was to clarify the pathologies of
      BPSD in AD patients. METHODS: Thirty patients with probable AD were included and
      underwent the following assessments: Mini Mental State Examination (MMSE), Clock
      Drawing Test (CDT), Story Recall Test (SRT), Behavioral pathology in Alzheimer's
      disease (BEHAVE-AD) and proton MRS ((1)H-MRS). None of them had been medicated
      for BPSD. RESULTS: The MRS study revealed that MMSE, CDT, and SRT scores were
      positively related to N-acetyl-aspartate (NAA)/creatine(Cr) and negatively
      related to myoinositol (mI)/Cr in the posterior cingulate gyrus, but not in the
      anterior cingulate gyrus. On the other hand, the scores obtained in two
      categories of BEHAVE-AD (delusional thought/ activity disturbances) were
      negatively related with NAA/Cr and positively related with mI/Cr in the anterior
      cingulate gyrus, but not in the posterior cingulate gyrus. CONCLUSION: We
      conclude that BPSD and the decline in cognitive function in AD might have
      separate pathologies.

PMID- 17540409
TI  - The community structure of human cellular signaling network.
AB  - Living cell is highly responsive to specific chemicals in its environment, such
      as hormones and molecules in food or aromas. The reason is ascribed to the
      existence of widespread and diverse signal transduction pathways, between which
      crosstalks usually exist, thus constitute a complex signaling network. Evidently,
      knowledge of topology characteristic of this network could contribute a lot to
      the understanding of diverse cellular behaviors and life phenomena thus come into
      being. In this presentation, signal transduction data is extracted from KEGG to
      construct a cellular signaling network of Homo sapiens, which has 931 nodes and
      6798 links in total. Computing the degree distribution, we find it is not a
      random network, but a scale-free network following a power-law of P(K)
      approximately K(-gamma), with gamma approximately equal to 2.2. Among three graph
      partition algorithms, the Guimera's simulated annealing method is chosen to study
      the details of topology structure and other properties of this cellular signaling
      network, as it shows the best performance. To reveal the underlying biological
      implications, further investigation is conducted on ad hoc community and sketch
      map of individual community is drawn accordingly. The involved experiment data
      can be found in the supplementary material.

PMID- 17540410
TI  - Emergent heterogeneity in declining tuberculosis epidemics.
AB  - Tuberculosis is a disease of global importance: over 2 million deaths are
      attributed to this infectious disease each year. Even in areas where tuberculosis
      is in decline, there are sporadic outbreaks which are often attributed either to
      increased host susceptibility or increased strain transmissibility and virulence.
      Using two mathematical models, we explore the role of the contact structure of
      the population, and find that in declining epidemics, localized outbreaks may
      occur as a result of contact heterogeneity even in the absence of host or strain
      variability. We discuss the implications of this finding for tuberculosis control
      in low incidence settings.

PMID- 17540411
TI  - Phosphorylation of Ser166 in RGS5 by protein kinase C causes loss of RGS
      function.
AB  - RGS5 is a member of regulators of G protein signaling (RGS) proteins that
      attenuate heterotrimeric G protein signaling by functioning as GTPase-activating
      proteins (GAPs). We investigated phosphorylation of RGS5 and the resulting change
      of its function. In 293T cells, transiently expressed RGS5 was phosphorylated by
      endogenous protein kinases in the basal state. The phosphorylation was enhanced
      by phorbol 12-myristate 13-acetate (PMA) and endothelin-1 (ET-1), and suppressed
      by protein kinase C (PKC) inhibitors, H7, calphostin C and staurosporine. These
      results suggest involvement of PKC in phosphorylation of RGS5. In in vitro
      experiments, PKC phosphorylated recombinant RGS5 protein at serine residues. RGS5
      protein phosphorylated by PKC showed much lower binding capacity for and GAP
      activity toward Galpha subunits than did the unphosphorylated RGS5. In cells
      expressing RGS5, the inhibitory effect of RGS5 on ET-1-induced Ca(2+) responses
      was enhanced by staurosporine. Mass spectrometric analysis of the phosphorylated
      RGS5 revealed that Ser166 was one of the predominant phosphorylation sites.
      Substitution of Ser166 by aspartic acid abolished the binding capacity to Galpha
      subunits and the GAP activity, and markedly reduced the inhibitory effect on ET-1
      induced Ca(2+) responses. These results indicate that phosphorylation at Ser166
      of RGS5 by PKC causes loss of the function of RGS5 in G protein signaling. Since
      this serine residue is conserved in RGS domains of many RGS proteins, the
      phosphorylation at Ser166 by PKC might act as a molecular switch and have
      functional significance.

PMID- 17540412
TI  - Statistical properties of ion channel records. Part I: relationship to the
      macroscopic current.
AB  - Macroscopic ion channel current can be derived by summation of the stochastic
      records of individual channel currents. In this paper, we present two probability
      density functions of single channel records that can uniquely determine the
      macroscopic current regardless of other statistical properties of records or the
      stochastic model of channel gating (presented often with stationary Markov
      models). We show that H(t), probability density function of channel opening
      events (introduced explicitly in this paper), and D(t), probability density
      function of the open duration (sometimes has named dwell time distribution as
      well), determine the normalized macroscopic current, G(t), through G(t) = P(t) -
      H(t) * Q(t) where P(t) is the cumulative density function of H(t), Q(t) is the
      cumulative density function of D(t), * is the symbol of convolution integral and
      G(t) is the macroscopic current divided by the amplitude of single channel
      current and the number of single channel sweeps. Compared to other equations for
      the macroscopic current, here the macroscopic current is expressed only in terms
      of the statistical properties of single channel current and not the stochastic
      model of ion channel gating or a conditioned form of macroscopic current. Single
      channel currents of an inactivating BK channel were used to validate this
      relationship experimentally too. In this paper, we used median filters as they
      can remove the unwanted noise without smoothing the transitions between open and
      closed states (compare to low pass filters). This filtering leads to more
      accurate measurement of transition times and less amount of missed events.

PMID- 17540413
TI  - Functional mechanisms of myocardial microcirculation in left ventricular
      hypertrophy: a hypothetical model of capillary remodeling post myocardial
      infarction.
AB  - OBJECTIVES: Left ventricular (LV) remodeling after myocardial infarction (MI) is
      characterized by myocyte hypertrophy and a disproportional capillary growth. We
      developed a hypothetical model of capillary remodeling mechanisms based on
      quantitative data of microcirculation determined by magnetic resonance (MR)
      imaging techniques and histology. METHODS: Perfusion and regional capillary blood
      volume (RBV) were quantified 8 and 16 weeks after MI (mean 27.0+/-2.9% of the
      left ventricle 16 weeks post MI) or sham operation in rats using MR imaging and
      were correlated with morphometric data. RESULTS: Maximum perfusion (ml/(g min))
      in the remote area decreased from 5.69+/-0.63 to 3.48+/-0.48 compared to sham
      animals (5.33+/-0.31, p</=0.01) and showed a close inverse relation to
      hypertrophy. In contrast, maximum RBV in the remote area was similar to that of
      sham animals (16.79+/-0.42% and 16.52+/-0.33%, respectively) and did not change
      over time. Thus, mean transit time (MTT) was longer in remote than in sham
      myocardium. Morphology revealed that hypertrophy was inversely related to
      capillary density which was associated with an increase in capillary cross
      sections. CONCLUSIONS: Perfusion data in synopsis with histological observations
      demonstrate that the functional capillary length increases during hypertrophy
      post MI which is consistent with the increase of the mean transit time. Despite a
      relative decrease in capillary density, RBV may be restored by an increase in the
      cross-sections. In the light of almost maximum oxygen extraction under normal
      conditions, this hypertrophy related remodeling may be deleterious for tissue
      supply.

PMID- 17540414
TI  - Habitual high and low consumers of artificially-sweetened beverages: effects of
      sweet taste and energy on short-term appetite.
AB  - This study investigated the effects of sweet taste and energy on subsequent short
      term appetite in female habitual high and low consumers of artificially-sweetened
      beverages. The study was based on the proposal that effects of sweet taste on
      appetite may differ as a result of the habitual experience of sweetness with or
      without energy. Following a repeated measures design, 10 female habitual high and
      10 female habitual low consumers of artificially-sweetened beverages consumed a
      non-sweet/low-energy, sweet/low-energy, and sweet/high-energy preload, and
      cumulative test meal intake (gram, kJ.), cumulative total intake (gram, kJ.), and
      subjective perceptions of appetite were subsequently assessed. Different effects
      of sweet taste were found in habitual high and low consumers of artificially
      sweetened beverages. Low consumers of artificially-sweetened beverages
      demonstrated an increase in appetite in response to sweet taste, whereas high
      consumers did not. Effects of energy on appetite did not differ between
      consumers. The effects of energy are unsurprising. The effects of sweet taste,
      however, are of interest. The lack of response to sweet taste in high consumers
      of artificially-sweetened beverages can be explained as a result of the repeated
      experience of sweetness without energy by these consumers. This lack of response
      suggests an adaptation to sweet taste as a result of the habitual dietary pattern
      of these consumers.

PMID- 17540415
TI  - Hyper-homeostatic learning of anticipatory hunger in rats.
AB  - Anticipatory hunger is a learnt increase in intake of food having a flavour or
      texture that predicts a long fast. This learning was studied in rats trained on a
      single food or a choice between protein-rich and carbohydrate-rich foods,
      presented for 1.5 h after 3 h without maintenance food at the start of the dark
      phase. Eight training cycles provided a pseudo-random sequence of 3 h and 10 h
      post-prandial fasts with a day on maintenance food between each training fast.
      The measure of anticipatory hunger is the difference over one 4-day cycle between
      the intake of test food having an odour predictive of the longer fast (TL) and
      intake of food with an odour cuing to the shorter fast (TS). Previous experiments
      showed that conditioning of preference for the odour before the shorter fast
      competes with learning to avoid hunger during the longer fast (anticipatory
      hunger), generating a cubic or quartic contrast. TL minus TS showed a strong
      cubic trend over 8 training cycles with both single and choice meals. There was a
      switch from preference for the short-fast odour at cycle 2 (TL-TS=-0.86 g) to a
      peak of anticipatory hunger at cycle 6 (TL-TS=1.57 g). We conclude that
      anticipatory hunger is learnt when a choice is given between protein-rich and
      carbohydrate-rich foods as well as on a single food. In addition, since
      anticipatory hunger extinguishes itself, such learning improves on negative
      feedback homeostasis with a feed-forward "hyper-homeostatic" mechanism.

PMID- 17540416
TI  - Measuring in vivo elasticities of Calvin cycle enzymes: network structure and
      patterns of modulations.
AB  - To measure the kinetics of enzymes, the proteins are usually assayed in vitro
      after isolation from their parent organisms. We make an attempt to show how one
      might determine enzyme elasticities in an intact system by a multiple modulation
      approach. Certain target enzymes are modulated in their activities and the
      changes in metabolite concentrations and flux rates upon the modulations are used
      to calculate the enzyme elasticities. Central to this approach is that the
      modulations must be independent of each other, and an algorithm is developed for
      finding all independent modulations that allow determining the elasticities of a
      given enzyme. This approach is applied to a mass-action model of the Calvin
      cycle. The goal is to determine the elasticities of as many enzymes as possible
      by modulating the activities of as few of them as possible. It is shown that the
      elasticities of 20 (out of 22) Calvin cycle enzymes can be determined by
      modulating just five reactions. Moreover, visualization of independence of
      modulations may be used to decompose the Calvin cycle into several sections that
      are independent of each other regarding flow of matter and information.

PMID- 17540417
TI  - An unusual C6-C6" linked flavonoid from Miconia cabucu (Melastomataceae).
AB  - Chromatographic fractionation of the methanolic extract from the leaves of
      Miconia cabucu Hoehne (Melastomataceae) afforded the first example of a C(6)
      C(6") linked flavone dimer, 5-hydroxy-4',7-dimethoxyflavone-(6-C-6'')-5''-hydroxy
      3''',4''',7''-trimethoxyflavone as well as the known compounds, quercetin-3-O
      alpha-l-rhamnopyranosyl-(2-->1)-O-beta-D-xylopyranoside, quercetin-3-O-alpha-l
      rhamnopyranoside, myricetin-3-O-alpha-l-rhamnopyranoside, quercetin-3-O-beta-D
      glucopyranoside, kaempferol-3-O-beta-D-(6''-coumaroyl)-glucopyranoside and gallic
      acid. Their chemical identities were established by application of NMR
      spectroscopic methods including 2D-NMR, as well as UV and ESI-MS analyses.

PMID- 17540418
TI  - In vivo 13C NMR determines metabolic fluxes and steady state in linseed embryos.
AB  - The dynamics of developing linseed embryo metabolism was investigated using (13)C
      labelling experiments where the real-time kinetics of label incorporation into
      metabolites was monitored in situ using in vivo NMR. The approach took advantage
      of the occurrence in this plant tissue of large metabolite pools - such as
      sucrose or lipids - to provide direct and quantitative measurement of the
      evolution of the labelling state within central metabolism. As a pre-requisite
      for the use of steady state flux measurements it was shown that isotopic steady
      state was reached within 3 h at the level of central intermediates whereas it
      took a further 6h for the sucrose pool. Complete isotopic and metabolic steady
      state took 18 h to be reached. The data collected during the transient state
      where label was equilibrated but the metabolic steady state was incomplete,
      enabled the rates of lipid and sucrose synthesis to be measured in situ on the
      same sample. This approach is suitable to get a direct assessment of metabolic
      time-scales within living plant tissues and provides a valuable complement to
      steady state flux determinations.

PMID- 17540419
TI  - Isoflavanones from Uraria picta and their antimicrobial activity.
AB  - Two isoflavanones, 5,7-dihydroxy-2'-methoxy-3',4'-methylenedioxyisoflavanone (2)
      and 4',5-dihydroxy-2',3'-dimethoxy-7-(5- hydroxyoxychromen-7yl)-isoflavanone (4)
      along with six known compounds including isoflavanones, triterpenes and steroids
      were isolated from the roots of Uraria picta. The structures of these compounds
      were established unambiguously by UV, IR, MS and a series of 1D and 2D NMR
      analyses. The minimum inhibitory concentrations (MIC) for these compounds were
      found to be in the range of 12.5-200 microg/ml against bacteria (both Gram
      positive and Gram negative) and fungi.

PMID- 17540420
TI  - The response to the trench diseases in World War I: a triumph of public health
      science.
AB  - The recent 90-year anniversary of the Battle of the Somme presents an opportunity
      to examine the public health response to the trench diseases, new conditions
      which arose in the trenches of World War I. Throughout history, there have been
      two views of epidemic disease: the configurationist and contagionist
      perspectives. Most doctors responding to the trench diseases, 'contingent
      contagionists', combined these two conceptions of disease. Because of the
      difficulty of finding a causative organism and the absence of effective
      treatment, the majority view became that these conditions were a product of the
      trench environment. Configurationism, with its emphasis on environmental and
      social determinants, seemed to provide the most obvious approaches for tackling
      the trench diseases. The diseases were effectively controlled using the tools of
      public health science: sanitary discipline and a battery of measures, such as
      improving trench construction, improving the diet, providing protective kit,
      regular bathing and treating lice infestation. The response demonstrates the
      triumph of public health science over new medical technologies. It also
      illustrates the importance of considering all the many determinants of health and
      of close surveillance, discipline and partnership working to counter ill-health.
      Although technology, training, doctrine and health beliefs change over time, the
      interaction between disease and environment remains the core challenge to public
      health practitioners.

PMID- 17540421
TI  - Experience in tuberculosis treatment through directly observed therapy short
      course in health centres and communities in Cambodia.

PMID- 17540422
TI  - Developing public health nursing: barriers perceived by community nurses.
AB  - OBJECTIVES: To understand the key issues for field nursing in developing their
      public health role within five primary care trusts (PCTs) in Merseyside, in the
      North West of England. DESIGN: Qualitative study. METHODS: Fourteen school nurses
      and 30 health visitors participated in 11 focus groups consisting of others from
      their profession working within the same PCT, and 24 practitioners responded to a
      questionnaire. RESULTS: The findings suggest that there are a number of shared
      obstacles that need to be overcome before the public health approach can be fully
      developed within community nursing. These include: the need for facilitation to
      deal with organisational change, lack of clarity around the public health role,
      inadequate administrative support, general practitioner attachment problems, poor
      interprofessional partnerships, competing priorities and resistance to change.
      CONCLUSIONS: The development of public health nursing in England envisaged in
      current government policy will not occur in full unless the kind of issues
      identified in this study are adequately addressed. This will require
      participative, interprofessional approaches to redesigning services by all
      relevant public health practitioners.

PMID- 17540423
TI  - Risk factors for surgically treated benign prostatic hyperplasia in Western
      Australia.
AB  - OBJECTIVE: To determine the relationship between personal, hormonal and lifestyle
      risk factors and surgically treated benign prostatic hyperplasia (BPH). MATERIALS
      AND METHODS: A population-based case-control study was conducted in Western
      Australia (WA) on men aged 40-75 years who were surgically treated at public and
      private hospitals for BPH during 2001-2002. Controls were recruited from the WA
      electoral roll. Cases and controls were compared with regard to demographic and
      lifestyle factors and proxy measures of hormonal status using logistic
      regression. Data were available for 398 cases and 471 controls. RESULTS: No
      associations with BPH were found for family history of prostate cancer in father
      or brother, serving in the military in a combat area, pattern of baldness,
      smoking status, obesity, alcohol intake and occupational physical activity. The
      only inverse relationship was observed with heavy alcohol drinking (>30g/day),
      however, this was not statistically significant. An increased risk of BPH, not
      statistically significant, was observed for British-born men compared to
      Australian born and for history of vasectomy. The analysis was repeated after
      excluding 28% of controls with moderate and severe symptoms of BPH and 7% of
      cases with mild symptoms prior to surgery, and our results remained essentially
      unchanged. CONCLUSIONS: The results suggest that there are few risk factors for
      BPH although perhaps country of birth, vasectomy and heavy alcohol consumption
      may be considered further.

PMID- 17540424
TI  - [Continuing medical education, assessing professional practice, accreditation.
      "What kind of validation can we claim?"].

PMID- 17540425
TI  - Treatment of common mental disorders in primary care in low- and middle-income
      countries.
AB  - Common mental disorders are responsible for up to 10% of the total global disease
      burden. The growing evidence base for the efficacy and cost-effectiveness of
      treatments for these disorders raises the possibility of delivering huge health
      and economic benefits. However, delivering these treatments in resource
      constrained settings is challenging. At least one-third of all patients seen in
      primary care in low- and middle-income countries present with common mental
      disorders. The majority are not recognised or are ineffectively treated. To
      address this problem, WHO advocates integrating mental health in primary care.
      However, the limited evidence base has impeded efforts to develop such services.

PMID- 17540426
TI  - Activation of p38 mitogen-activated protein kinase by celecoxib oppositely
      regulates survivin and gamma-H2AX in human colorectal cancer cells.
AB  - Cancer cells express survivin that facilitates tumorigenesis. Celecoxib has been
      shown to reduce human colorectal cancers. However, the role and regulation of
      survivin by celecoxib in colorectal carcinoma cells remain unclear. Treatment
      with 40-80 muM celecoxib for 24 h induced cytotoxicity and proliferation
      inhibition via a concentration-dependent manner in RKO colorectal carcinoma
      cells. Celecoxib blocked the survivin protein expression and increased the
      phosphorylation of H2AX at serine-193 (gamma-H2AX). The survivin gene knockdown
      by transfection with a survivin siRNA revealed that the loss of survivin
      correlated with the expression of gamma-H2AX. Meanwhile, celecoxib increased
      caspase-3 activation and apoptosis. Celecoxib activated the phosphorylation of
      p38 mitogen-activated protein (MAP) kinase. The phosphorylated proteins of p38
      MAP kinase and gamma-H2AX were observed in the apoptotic cells. SB203580, a
      specific p38 MAP kinase inhibitor, protected the survivin protein expression and
      decreased the levels of gamma-H2AX and apoptosis in the celecoxib-exposed cells.
      The blockade of survivin expression increased the celecoxib-induced cytotoxicity;
      conversely, overexpression of survivin by transfection with a survivin-expressing
      vector raised the cancer cell proliferation and resisted the celecoxib-induced
      cell death. Our results provide for the first time that p38 MAP kinase
      participates in the down-regulation of survivin and subsequently induces the
      activation of gamma-H2AX for mediating apoptosis following treatment with
      celecoxib in human colorectal cancer cells.

PMID- 17540427
TI  - Acrylamide effects on kinesin-related proteins of the mitotic/meiotic spindle.
AB  - The microtubule (MT) motor protein kinesin is a vital component of cells and
      organs expressing acrylamide (ACR) toxicity. As a mechanism of its potential
      carcinogenicity, we determined whether kinesins involved in cell division are
      inhibited by ACR similar to neuronal kinesin [Sickles, D.W., Brady, S.T.,
      Testino, A.R., Friedman, M.A., and Wrenn, R.A. (1996). Direct effect of the
      neurotoxicant acrylamide on kinesin-based microtubule motility. Journal of
      Neuroscience Research 46, 7-17.] Kinesin-related genes were isolated from rat
      testes [Navolanic, P.M., and Sperry, A.O. (2000). Identification of isoforms of a
      mitotic motor in mammalian spermatogenesis. Biology of Reproduction 62, 1360
      1369.], their kinesin-like proteins expressed in bacteria using recombinant DNA
      techniques and the effects of ACR, glycidamide (GLY) and propionamide (a non
      neurotoxic metabolite) on the function of two of the identified kinesin motors
      were tested. KIFC5A MT bundling activity, required for mitotic spindle formation,
      was measured in an MT-binding assay. Both ACR and GLY caused a similar
      concentration-dependent reduction in the binding of MT; concentrations of 100
      microM ACR or GLY reduced its activity by 60%. KRP2 MT disassembling activity was
      assayed using the quantity of tubulin disassembled from taxol-stabilized MT. Both
      ACR and GLY inhibited KRP2-induced MT disassembly. GLY was substantially more
      potent; significant reductions of 60% were achieved by 500 microM, a comparable
      inhibition by ACR required a 5 mM concentration. Propionamide had no significant
      effect on either kinesin, except KRP2 at 10 mM. This is the first report of ACR
      inhibition of a mitotic/meiotic motor protein. ACR (or GLY) inhibition of kinesin
      may be an alternative mechanism to DNA adduction in the production of cell
      division defects and potential carcinogenicity. We conclude that ACR may act on
      multiple kinesin family members and produce toxicities in organs highly dependent
      on microtubule-based functions.

PMID- 17540428
TI  - Identification and characterization of DTX-5c and 7-hydroxymethyl-2-methylene
      octa-4,7-dienyl okadaate from Prorocentrum belizeanum cultures by LC-MS.
AB  - The main toxins produced by the dinoflagellate Prorocentrum belizeanum, DTX5c and
      7-hydroxymethyl-2methylene-octa-4,7 dienyl okadaate, were studied by liquid
      chromatography-coupled with ion trap mass spectrometry (LC-MS/MS). Their
      retention times (RTs) and fragmentation patterns were established, in particular
      those of DTX5c, as there is a lack of data about these water soluble OA sulphated
      derivatives. As an application of the LC-MS methodology, a sample of the toxic P.
      belizeanum culture was analysed for these metabolites. Both metabolites were
      detected in cells as majority compounds, whereas levels of these compounds in the
      culture media were undetectable.

PMID- 17540429
TI  - Fuzzy auto-tuning PID control of multiple joint robot driven by ultrasonic
      motors.
AB  - A three-joint robot is directly driven by ultrasonic motors with advantage of
      high torque at low speed. The speed of the ultrasonic motors is actually
      controlled by regulating their operating frequencies. The kinematic and kinetic
      analyses of the robot have been carried out using Adams. Due to the lack of
      accurate control model of ultrasonic motors and the time-varying motor
      parameters, a fuzzy auto-tuning proportional integral derivative (PID) controller
      for the robot is experimented, in which a simple method to tune parameters of the
      PID type fuzzy controller on-line is developed and a new position-speed feedback
      strategy is proposed and implemented. The effectiveness of the proposed control
      strategy and fuzzy logic controller is verified by experimental investigation.

PMID- 17540430
TI  - The genome sequence of the multinucleocapsid nucleopolyhedrovirus of the Chinese
      oak silkworm Antheraea pernyi.
AB  - The complete genome sequence of the Liaoning isolate of the Antheraea pernyi
      multinucleocapsid nucleopolyhedrovirus (AnpeMNPV) was determined. The viral
      genome size is 126,246 bp, relatively GC-rich (53.5% G+C), with 145 predicted
      open reading frames (ORFs) of more than 50 amino acids, accounting for more than
      97% of the genome. 97% of the ORFs have predicted functions or homologues in
      other baculoviruses. There are six homologous repeat regions (hrs) and two bro
      homologues, which are associated with regions of genome instability. The virus
      lacks the p35 homologue but encodes two members of the inhibitors of apoptosis
      (iap) gene family. The presence of a gp64 homologue in the AnpeMNPV genome and
      results from gene parity plot and phylogenetic analysis using the 29 core
      baculovirus genes clearly classify AnpeMNPV as a group I NPV. The divergence of
      genome sequences in two geographical NPV isolates suggests of great genetic
      heterogeneity of baculovirus populations in nature.

PMID- 17540431
TI  - Identification of pets and raccoons as sources of bacterial contamination of
      urban storm sewers using a sequence-based bacterial source tracking method.
AB  - In urbanized areas, contaminated storm sewers can feed high bacterial levels into
      free-flowing streams and rivers. Although illicit connections sometimes cause
      contamination, urban wildlife and free-roaming domesticated or feral pets may be
      another source. After eliminating illicit connections as sources of high levels
      of Escherichia coli in two storm sewers tributary to the Huron River in southeast
      Michigan, the roles of urban wildlife, pets, humans, and birds were investigated
      using a sequence-based bacterial source tracking technology. After enumeration,
      E. coli were isolated from water samples collected during spring to fall, 2005.
      Sequences in the gene beta-glucuronidase of each isolate were compared to
      sequences of reference strains from humans, raccoons, pets (cats and dogs), and
      birds. The highest percentage source for six of ten events was pets (ANOVA,
      p=0.005). Among isolates attributed to pets, strains from cats occurred more
      frequently on seven of nine events in which pets had a non-zero probability. High
      raccoon percentages (up to 60%) occurred in late summer and fall, and varied
      significantly more than in the spring (F-test), possibly reflecting urban raccoon
      den-site mobility. The sequence-based bacterial source tracking method suggests
      that feces from pets and raccoons are important contributors to urban storm
      sewers.

PMID- 17540432
TI  - Freeze/thaw and pH effects on freshwater dissolved organic matter fluorescence
      and absorbance properties from a number of UK locations.
AB  - The UV-visible and fluorescence excitation-emission matrix spectrophotometric
      properties of dissolved organic matter (DOM) were compared for the effects of
      both pH and freeze/thaw on a wide range of freshwater DOM samples from the United
      Kingdom. It was observed that the spectrophotometric properties of our freshwater
      samples were sensitive to pH and that the recorded change varies with
      fluorescence and absorbance intensity, DOC concentration and the wavelength
      observed. Large and variable responses to pH were particularly severe at extremes
      of pH, but within the natural levels typically observed in freshwaters the
      response to pH was limited. For the same sample set large and variable responses
      were observed when subjected to freeze/thaw. From our data, knowledge of the
      original properties cannot be used to determine the amount of change that will
      occur with freezing and subsequent thawing. It is therefore recommended that in
      future research, to maintain the natural signal of the DOM, analysis is conducted
      at natural pH and without freezing to facilitate ease of comparison between
      studies. Our results also have implications for studies that utilise
      spectrophotometric techniques to investigate long-term trends in dissolved
      organic carbon in rivers. Spectrophotometric parameters from upland derived
      samples show varied responses of samples to pH and there is clear potential to
      complicate trends in the interpretation of long-term water colour data if pH is
      changing over time in a system or if samples are treated with different storage
      protocols with respect to acidification and freezing.

PMID- 17540433
TI  - Particle size distribution from a GTL engine.
AB  - Measurements of exhaust particle number concentration and size distribution from
      an engine fueled with GTL at different engine loads and speeds were carried out
      by using a two-stage dilution system. The results for GTL were compared with
      those from the original engine fueled with diesel. The fuel composition and
      engine operation condition had significant effects on the exhaust particle size
      distribution, the total exhaust particle number and volume concentrations. For
      both fuels, the load had no significant influence on the total exhaust particle
      number concentration at middle speed, while the total exhaust particle number
      concentration increased with the increase of the load at high speed. At 1400 rpm
      and 2200 rpm, the total exhaust particle volume concentration increased as the
      load increased for both fuels. GTL was found to be a "cleaner" fuel. Compared
      with diesel, under the same operation conditions, the total exhaust particle
      number concentrations decreased 18-92%, and the total exhaust particle volume
      concentrations for GTL decreased 21-59%.

PMID- 17540434
TI  - Variations in amounts and potential sources of volatile organic chemicals in new
      cars.
AB  - This study examines inter-brand, intra-brand and intra-model variations in
      volatile organic chemical (VOC) levels inside new cars. The effect of temperature
      on interior VOC levels was examined using model automobiles with and without the
      air-conditioning running. Potential sources of VOC were assessed by comparing VOC
      levels with two interior trims (leather and fabric) and by analyzing VOC
      emissions from various interior components. Five brands of new car, both domestic
      and imported, were tested. Twelve targeted VOCs were collected on solid sorbents
      and analyzed using thermal desorption and GC/FID. VOCs from interior parts and
      adhesives were identified using solid phase micro-extraction (SPME) coupled with
      GC/MS. The VOC concentrations varied markedly among brands and within models, and
      individual VOC levels ranged from below the detection limit (a few mug per cubic
      meter) to thousands of mug per cubic meter. The intra-model variability (mean,
      47%) in the VOC levels was approximately 50% that within each brand (mean, 95%).
      Although interior trim levels affected VOC levels, the effects differed among
      brands. Reduction of the cabin temperature reduced most VOC levels, but the
      impact was not statistically significant. Screening tests for VOCs from interior
      parts revealed that butylated hydroxytoluene (BHT), a common anti-oxidant, was
      the most common chemical. Long-chain aliphatic hydrocarbons, particularly C14
      C17, were identified in most grease (lubricant) samples, and toluene and xylenes
      were ubiquitously present in adhesive samples. Process-related compounds, such as
      plasticizer, were also identified in interior parts. In-cabin VOC levels varied
      significantly among makes/models and interior trims. Concerned consumers should
      purchase older new cars from manufacturers since VOC levels inside car cabins
      normally declines over time. Improved processes or materials with lower VOC
      emission potential should be used to minimize in-cabin VOC sources for new cars.

PMID- 17540435
TI  - Comparison of the Revised Air Quality Index with the PSI and AQI indices.
AB  - Air pollution indices are commonly used to indicate the level of severity of air
      pollution to the public. The Pollution Standards Index (PSI) was initially
      established in response to a dramatic increase in the number of people suffering
      respiratory irritation due to the deteriorating air quality. The PSI was
      subsequently revised and implemented by the USEPA in 1999, and became known as
      the Air Quality Index (AQI) that includes data relating to particle suspension,
      PM2.5, and a selective options of either 8-hour or 1-hour ozone concentration
      during increased O3 periods. Yet, the costs of launching a network of PM2.5
      monitoring stations are prohibitively high for many countries to implement the
      AQI from the PSI system in the foreseeable future. Therefore, the purpose of this
      research is to discuss the optimal method of assessing air quality using the
      latest developed Revised AQI (RAQI), a system that serves as an alternative to
      the PSI and AQI systems. The feasibility, effectiveness, and the differences
      between RAQI, AQI, and PSI in their applications to several air pollution
      conditions are also studied in this research. The results show that southern
      Taiwan's suspended particulates have significantly greater impact on PM2.5/PM10
      ratios than in central and northern metropolitan areas, and that the ratios are
      higher in Taiwan as a whole compared to many other countries. We also found that
      the RAQI shows more significant results compared to the PSI and AQI as it has a
      wider coverage of the range of pollutant concentration levels.

PMID- 17540436
TI  - Expression level of Wilms tumor 1 (WT1) protein has limited prognostic value in
      epithelial ovarian cancer: from the Danish "MALOVA" ovarian cancer study.
AB  - OBJECTIVES: To determine the WT1 expression level in tumor tissues from 774 women
      with an epithelial ovarian tumor. Secondly, to evaluate whether WT1 tissue
      expression levels correlate with clinico-pathological parameters and finally to
      investigate the prognostic value of WT1 expression levels in ovarian cancer (OC)
      patients. METHODS: Using tissue array we analyzed the WT1 expression level in
      tissues from 186 women with Low Malignant Potential tumors (LMP) (160 stage I, 5
      stage II and 21 stage III) and 560 OC patients (160 stage I, 60 stage II, 289
      stage III and 51 stage IV). RESULTS: Using 10% as cut-off level for WT1
      overexpression an overall of 19% LMPs and 17% carcinomas, respectively, were
      found positive. For both, a higher proportion of positive tumors was found in the
      serous subtype compared to other histological subtypes (p<0.0001). Kaplan-Meier
      survival analysis stratified by FIGO stage performed on cases using a 10% cut-off
      showed a shorter disease specific survival in patients with a positive WT1
      expression in the tumor tissue. In a Cox survival analysis including 559 stage I
      to IV OC prognostic factors included FIGO stage (II vs. I: HR=2.74, 95% CI: 1.42
      5.29; III vs. II: HR=2.23, 95% CI: 1.49-3.36; IV vs. III: HR=1.75, 95% CI: 1.25
      2.44), residual tumor after primary surgery (HR=2.82, 95% CI: 1.87-4.26), age at
      diagnosis (HR=1.02, 95% CI: 1.01-1.03), histological grade 3 of tumor versus
      grade 1 (grade 2 vs. grade 1: HR=1.31, 95% CI: 0.95-1.81; grade 3 vs. grade 1:
      HR=1.51, 95% CI: 1.08-2.09) and other histological tumor types vs. serous
      (mucinous vs. serous: HR=0.91, 95% CI: 0.53-1.56; endometrioid vs. serous:
      HR=1.02, 95% CI: 0.69-1.50; other histological types vs. serous: HR=1.40, 95% CI:
      1.01-1.95). WT1 expression (HR=1.22, 95% CI: 0.94-1.59) had statistically no
      significant independent impact on survival. CONCLUSION: In conclusion, based on
      our analyses we found that WT1 expression in clinical settings may be of limited
      prognostic value in Danish OC patients.

PMID- 17540437
TI  - Overexpression of epidermal growth factor type-1 receptor (EGF-R1) in cervical
      cancer: implications for Cetuximab-mediated therapy in recurrent/metastatic
      disease.
AB  - OBJECTIVES: To evaluate and compare epidermal growth factor type-1 receptor (EGF
      R1) expression in short term and established cervical cancer cell lines generated
      from primary and metastatic/recurrent sites of disease. To evaluate the
      sensitivity of cervical cancer cell lines to treatment with a chimeric MAb
      against EGFR-1 (Cetuximab). METHODS: EGFR-1 expression was evaluated by flow
      cytometry on 22 cervical cancer cell lines including 14 primary cervical cancer
      cell lines obtained from cervical biopsies (11 patients) and recurrent sites of
      disease (three patients) as well as eight established cell lines. Tumor cell
      lines were tested for sensitivity to Cetuximab-mediated complement-dependent
      cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC) in 51Cr
      release assays. Finally, Cetuximab-mediated inhibition of cell proliferation was
      also tested. RESULTS: Fourteen out of fourteen (100%) primary tumors and seven
      out of eight (87.5%) established cervical cancer cell lines expressed EGFR-1 by
      flow cytometry. Cell lines from recurrent/metastatic sites of disease expressed
      higher levels of EGFR-1 when compared to those obtained from primary sites
      (p>0.05). Minimal CDC was detected in the majority of cervical cancer cell lines
      exposed to complement+/-Cetuximab in the absence of peripheral blood lymphocytes
      (PBL). In contrast, cervical tumor cell lines were found highly sensitive to
      Cetuximab-mediated ADCC when challenged with PBL from either healthy donors or
      cervical cancer patients. Importantly, ADCC was further increased in the presence
      of complement. Finally, tumor proliferation was significantly inhibited by
      Cetuximab in all cervical tumors tested. CONCLUSIONS: EGFR-1 is highly expressed
      in primary and recurrent cervical tumors. Cetuximab might be a novel and
      attractive therapeutic strategy in patients harboring chemotherapy-resistant,
      recurrent, or metastatic cervical cancer.

PMID- 17540438
TI  - Gynecologic Oncology Group risk groups for vulvar carcinoma: improvement in
      survival in the modern era.
AB  - OBJECTIVE: Patients with vulvar cancer were stratified into risk groups for
      survival based on surgicopathologic findings from a prospective study conducted
      by the Gynecologic Oncology Group from 1977-1984. The purpose of this study is to
      reassess these risk groups in patients treated in an era of contemporary
      management. METHODS: Patients with vulvar carcinoma were identified from 1990
      2005 for retrospective analysis. Charts were abstracted for clinical,
      histopathologic and surgical data, and patients stratified into four risk groups
      for survival based on the clinical size of tumor and extent of lymph node
      metastasis. Univariate and multivariate characteristics were evaluated and 5-year
      survival determined by Kaplan-Meier method. RESULTS: 175 patients were identified
      that underwent surgical management with a median age at diagnosis of 59.9 years.
      Stage distribution included: I (n=89, 51%), II (n=53, 30%), III (n=29, 17%), and
      IV (n=4, 2%). Stratification into risk groups included: minimal (n=89, 51%), low
      (n=69, 40%), intermediate (n=11, 6%), and high (n=6; 3%). The survival rate was
      100%, 97%, 82% and 100%, respectively, at median follow-up of 54.5 months.
      Comparatively, the survival rates for historic groups were 97.9%, 87.4%, 74.8%
      and 29.0%. Using multivariate analysis, age (p=0.04) and lymph node metastasis
      (p=0.009) were predictive of survival. CONCLUSIONS: Survival among the minimal
      and low risk groups is preserved in spite of less radical surgery. 5-year
      survival rate for intermediate and high risk patients also appears to be
      improved. This is likely a result of advancement in adjuvant chemo-radiation and
      a younger patient population that presents with less advanced disease.

PMID- 17540439
TI  - Lobular endocervical glandular hyperplasia as a presumed precursor of cervical
      adenocarcinoma independent of human papillomavirus infection.
AB  - OBJECTIVES: The aim of this study was to investigate differences in the process
      of carcinogenesis between adenocarcinoma coexistent with LEGH and conventional
      adenocarcinoma. And we intend to describe appropriate treatment plans for LEGH in
      this study. METHODS: Using the surgical pathology files of patients who visited
      the University of Yamanashi Hospital, Yamanashi Central Hospital and Kofu
      Municipal Hospital between 1996 and 2005, pathological diagnoses were reevaluated
      based on criteria for the diagnosis of LEGH by Nucci et al. As for the cases
      including adenocarcinoma with LEGH: (a) we created a map showing position of the
      LEGH component and adenocarcinoma component and squamo-columnar junction (SCJ) in
      HE-stained specimens, (b) immunohistochemical staining was performed using
      antibodies to CEA, HIK1083 and p53, and (c) detection of HPV DNA was performed
      using PCR and in situ hybridization (ISH). RESULTS: Endocervical adenocarcinoma
      was observed coexistent with LEGH in 5 cases (19.2%). (a) LEGH was located in a
      remote place from the SCJ. Sizes of lesions in the 5 cases ranged from 18 to 35
      mm in width and 7 to 16 mm in depth. (b) HIK1083 was diffusely immunopositive in
      the cytoplasm of LEGH component and focal immunopositive in 4 cases with
      adenocarcinoma component. Immunopositivity for CEA was seen in the cytoplasm of
      adenocarcinoma component in 4 cases. Immunopositivity for p53 was seen in
      adenocarcinoma component nuclei in 2 cases. (c) HPV DNA was not detected using
      PCR and ISH in either LEGH or adenocarcinoma components. CONCLUSIONS: The present
      study suggests that clear differences exist in the process of carcinogenesis
      between adenocarcinoma associated with LEGH and conventional adenocarcinoma. LEGH
      may represent a precursor of cervical adenocarcinoma independent of HPV
      infection. As LEGH displays characteristics of precancerous mucinous
      adenocarcinoma, surgical treatment should be considered for LEGH growing beyond a
      certain size.

PMID- 17540440
TI  - The 5-HT3 receptor partial agonist MD-354 (meta-chlorophenylguanidine) enhances
      the discriminative stimulus actions of (+)amphetamine in rats.
AB  - The effect of the 5-HT3 receptor partial agonist MD-354 (meta
      chlorophenylguanidine) was examined on the discriminative stimulus produced by
      (+)amphetamine. Using male Sprague-Dawley rats trained to discriminate 1.0 mg/kg
      (i.p.) of (+)amphetamine from saline vehicle (VI 15-s schedule of reinforcement)
      in a two-lever operant procedure for appetitive reward, tests of stimulus
      generalization (substitution) and antagonism showed that MD-354 neither
      substituted for, nor antagonized, the amphetamine stimulus at the doses
      evaluated. Administration of (+)amphetamine doses in combination with a fixed
      (i.e., 1.0 mg/kg) dose of MD-354 shifted the (+)amphetamine dose-response curve
      to the left such that, following 0.3 mg/kg of (+)amphetamine, stimulus
      generalization occurred. Furthermore, MD-354 doses of 0.1, 0.3 and 1.0 mg/kg, but
      not doses of 0.01, 0.5, 1.5 or 3.0 mg/kg (i.p.), administered in combination with
      the ED(50) dose (0.33 mg/kg) of (+)amphetamine resulted in stimulus
      generalization (i.e., >80% drug-appropriate responding). It is concluded that
      even though MD-354 lacks amphetamine-like central stimulant actions of its own it
      can modulate the discriminative stimulus effects of (+)amphetamine in rats.

PMID- 17540441
TI  - Effect of antioxidant supplementation on semen quality and reactive oxygen
      species of frozen-thawed canine spermatozoa.
AB  - The objective of this study was to evaluate post-thaw quality of frozen dog semen
      processed with diluents containing different antioxidants. Ejaculates were
      collected, pooled and evaluated for concentration, motility, rapid steady forward
      movement (RSF movement), viability, acrosomal integrity and by the hypo-osmotic
      swelling test. Also, superoxide production, hydroxyl radicals and total reactive
      oxygen species (tROS) were determined. The pool was divided in seven aliquots,
      for control and test conditions, which were processed for cryopreservation. The
      sperm pellets were diluted to a final concentration of 200x10(6)sperm/ml with
      TRIS-glucose-egg yolk extender containing one of the following supplements:
      vitamin C (1.5mM), NAC (N-acetyl-l-cysteine; 1.5mM), taurine (0.6mM), catalase
      (300U/ml), vitamin E (0.3mM) and B16 [5-(4-dimethylamino-phenyl)-2-phenyl-penta
      2,4-dienoic acid; 0.3mM]. Post-thaw semen evaluation showed that mean (+/-S.E.M.)
      motility was increased (p<0.001) after addition of catalase (49.75+/-3.63 versus
      39.00+/-2.90 in controls), whereas more spermatozoa with RSF movement were
      observed (p<0.001) after the catalase, NAC and vitamin E treatments (31.75+/
      3.46, 28.00+/-3.27, 26.75+/-3.15, respectively, versus 17.00+/-2.26 in controls).
      Viability was increased (p<0.001) after addition of catalase, taurine, NAC and
      tocopherol (66.00+/-3.03, 61.90+/-2.48, 60.60+/-1.93 and 60.50+/-4.12,
      respectively, versus 51.70+/-2.81 in controls). The percentage of swollen
      spermatozoa was increased after addition of catalase and taurine (61.75+/-1.61
      and 61.25+/-1.49, respectively, versus 55.65+/-1.64 in controls). Acrosomal
      integrity was not influenced in any case. B16 addition had adverse effects on all
      parameters evaluated. None of the reactive oxygen species were significantly
      reduced post-thaw in antioxidant treated semen. The results suggest that catalase
      had the most pronounced effect in improving post-thaw quality of canine
      spermatozoa.

PMID- 17540442
TI  - Intra-ovarian regulation of follicular development and oocyte competence in farm
      animals.
AB  - In both mono-ovulatory species, such as cattle, and poly-ovulatory species, such
      as pigs, the interactions among extra-ovarian gonadotropins, metabolic hormones
      and intra-ovarian growth factors determine the continued development of
      follicles, the number of follicles that ovulate and the developmental competence
      of the ovulated oocyte. FSH and then subsequently LH are the main hormones
      regulating antral follicle growth in both mono- and poly-ovular species. However,
      a range of intra-ovarian growth factors, such as insulin-like growth factors
      (IGFs) and bone morphogenetic proteins (BMPs), are expressed throughout follicle
      and oocyte development and interact with gonadotropins to control follicle
      maturation. In addition, environmental factors such as nutrition, including both
      the amount and composition of the diet consumed prior to ovulation, can influence
      follicle development and the quality of the oocyte. Recent progress in our
      understanding has resulted in the development of diets that enhance oocyte
      quality and improve pregnancy rate in both pigs and cattle. In conclusion,
      despite some species-specific differences, similar interacting mechanisms control
      follicular development and influence oocyte quality.

PMID- 17540443
TI  - Spatial and temporal changes in infaunal communities inhabiting soft-bottoms
      affected by brine discharge.
AB  - The discharge of an effluent of high salinity from reverse osmosis desalination
      plants has a strong impact on marine communities. The aim of this study was to
      examine the effect of brine discharge over soft bottom communities along the
      Alicante coast (Southeast Spain) over a two year period. Changes in the infaunal
      assemblage were analysed using univariate and multivariate techniques. Each year
      we sampled along three transects at three depths (4, 10 and 15m) during winter
      and summer. We observed a substitution of a community characterized by the
      presence of Polychaeta, Crustacea and Mollusca, for another dominated by
      nematodes (up to 98%), in the stations closer to the discharge where salinity
      values exceed 39 psu.

PMID- 17540444
TI  - Isoelectric profiles of human erythropoietin are different in serum and urine.
AB  - By adding a step of immunoaffinity to the method we had previously developed for
      analysing erythropoietin (EPO) in urine, we were able to study the isoelectric
      profiles of this hormone in human serum samples. This method was sensitive enough
      to investigate samples presenting physiological levels of this hormone.
      Comparison with the corresponding profiles in urine showed that natural EPO was
      systematically more acidic in urine. The acidification process, which was not
      patent in the non-human primate Cynomolgus macaque, clearly also affected
      recombinant EPO when injected into humans. This process was unrelated to any
      enzymatic activity in urine since the incubation of natural or recombinant EPO in
      urine induced no transformation of their isoelectric profiles. The nature and
      mechanism of the structural modifications occurring during the renal handling of
      this hormone remain to be investigated.

PMID- 17540445
TI  - A critical review of the effects of gold cyanide-bearing tailings solutions on
      wildlife.
AB  - Wildlife deaths associated with cyanide-bearing mine waste solutions have plagued
      the gold mining industries for many years, yet there is little published data
      showing the relationship between wildlife mortality and cyanide toxicity. A gap
      of knowledge exists in monitoring, understanding the causal relationships and
      managing risks to wildlife from cyanide-bearing waste solutions and tailings.
      There is a need for the gold industry to address this issue and to meet the
      International Cyanide Management Code (ICMC) guidelines. The perceived extent of
      the issue varies, with one study finding the issue inadequately monitored and
      wildlife deaths grossly underestimated. In Nevada, USA during 1990 and 1991, 9512
      carcasses were reported of over 100 species, although there was underestimation
      due to reporting being voluntary. Of these, birds comprised 80-91% of vertebrate
      carcasses reported annually. At Northparkes, Australia in 1995, it was initially
      estimated that 100 bird carcasses were present by mine staff following a tailings
      incident; when a thorough count was conducted, 1583 bird carcasses were recorded.
      Eventually, 2700 bird deaths were documented over a four-month period. It is
      identified that avian deaths are usually undetected and significantly
      underestimated, leading to a perception that a risk does not exist. Few
      guidelines and information are available to manage the risks of cyanide to
      wildlife, although detoxification, habitat modification and denying wildlife
      access have been used effectively. Hazing techniques have proven ineffective.
      Apparently no literature exists that documents accurate wildlife monitoring
      protocols on potentially toxic cyanide-bearing mine waste solutions or any
      understanding on the analysis of any derived dataset. This places the onus on
      mining operations to document that no risk to wildlife exists. Cyanide-bearing
      tailings storage facilities are environmental control structures to contain
      tailings, a standard practice in the mining industry. Cyanide concentrations
      below 50 mg/L weak-acid-dissociable (WAD) are deemed safe to wildlife but are
      considered an interim benchmark for discharge into tailings storage facilities
      (TSFs). Cyanide is a fast acting poison, and its toxicity is related to the types
      of cyanide complexes that are present. Cyanide in biota binds to iron, copper and
      sulfur-containing enzymes and proteins required for oxygen transportation to
      cells. The accurate determination of cyanide concentrations in the field is
      difficult to achieve due to sampling techniques and analytical error associated
      with loss and interferences following collection. The main WAD cyanide complexes
      in gold mine tailings are stable in the TSF environment but can release cyanide
      ions under varying environmental conditions including ingestion and absorption by
      wildlife. Therefore distinction between free, WAD and total cyanide forms in
      tailings water for regulatory purposes is justified. From an environmental
      perspective, there is a distinction between ore bodies on the basis of their
      copper content. For example, wildlife deaths are more likely to occur at mines
      possessing copper-gold ores due to the formation of copper-cyanide complexes
      which is toxic to birds and bats. The formation of copper-cyanide complex occurs
      preferentially to gold cyanide complex indicating the relative importance of
      economic vs. environmental considerations in the tailings water. Management of
      cyanide to a perceived threshold has inherent risks since cyanide has a steep
      toxicity response curve; is difficult to accurately measure in the field; and is
      likely to vary due to variable copper content of ore bodies and ore blending.
      Consequently, wildlife interaction needs to be limited to further reduce the
      risks. A gap in knowledge exists to design or manage cyanide-bearing mine waste
      solutions to render such facilities unattractive to at-risk wildlife species.
      This gap may be overcome by understanding the wildlife behaviour and habitat
      usage of cyanide-bearing solutions.

PMID- 17540446
TI  - Omega-3 fatty acids and the benefits of fish consumption: is all that glitters
      gold?
AB  - In recent years, a number of studies have clearly remarked the nutritional
      benefits of fish consumption: proteins, vitamins, minerals, and especially omega
      3 polyunsaturated fatty acids (PUFAs), which may protect against several adverse
      health effects, including coronary heart disease mortality and stroke. However,
      some concerns about potential health risks derived from the environmental
      contaminants found in fish have been also raised. Therefore, balancing adequately
      the risks and benefits of fish consumption is currently a
      nutritional/environmental health key issue. In this paper, the most recent
      available scientific information concerning this issue is reviewed. It is
      concluded that although it seems evident that fish must be an important part of a
      balanced diet, to choose the most suitable species in terms of levels of PUFAs
      and pollutants, the frequency of consumption, and the meal size are essential
      aspects to balance benefits and risks of a regular consumption.

PMID- 17540447
TI  - Retinal vessel caliber and microvascular and macrovascular disease in type 2
      diabetes: XXI: the Wisconsin Epidemiologic Study of Diabetic Retinopathy.
AB  - OBJECTIVE: To describe the relationship of retinal arteriolar and venular
      calibers to the long-term incidence of microvascular and macrovascular
      complications in people with type 2 diabetes. DESIGN: Population-based
      prospective study. PARTICIPANTS: One thousand three hundred seventy persons
      diagnosed to have diabetes at > or =30 years of age in south central Wisconsin
      participated in the baseline examination from 1980 to 1982, 987 in the 4-year
      follow-up, and 533 in the 10-year follow-up. METHODS: Computer-assisted grading
      was used to determine the average caliber of retinal arterioles (central retinal
      arteriolar equivalent [CRAE]) and retinal venules (central retinal venular
      equivalent [CRVE]) at all examinations. MAIN OUTCOME MEASURES: Incidence and
      progression of diabetic retinopathy; incidence of proliferative diabetic
      retinopathy and macular edema; incidence of nephropathy, neuropathy, and lower
      extremity amputation; and ischemic heart disease, stroke, and overall mortality.
      RESULTS: While adjusting for other factors, smaller CRAE was associated with the
      14-year cumulative incidence of lower extremity amputation (odds ratio [OR],
      first vs. second to fourth quartiles, 2.20; 95% confidence interval [CI], 1.14
      4.24; P = 0.02), 22-year all-cause mortality (hazard ratio [HR], 1.18; 95% CI,
      1.02-1.38; P = 0.03), and 22-year stroke mortality (HR, 1.47; 95% CI, 1.04-2.07;
      P = 0.03) but not with the other end points. Larger CRVE was associated with the
      14-year incidence of diabetic nephropathy (OR, fourth vs. first to third
      quartiles, 2.08; 95% CI, 1.47-2.94; P<0.001) and 22-year stroke mortality (HR,
      1.71; 95% CI, 1.20-2.44; P = 0.003) but with none of the other end points.
      CONCLUSIONS: Retinal vessel caliber is independently associated with risk of
      incident nephropathy, lower extremity amputation, and stroke mortality in persons
      with type 2 diabetes. Measurement of retinal vessel caliber from photographs may
      provide additional information for the prediction of these events.

PMID- 17540448
TI  - Selective guanosine binding and cytotoxicity of a benzimidazole derived dinickel
      complex.
AB  - A water-soluble dinickel(II) complex of ethylene glycol-bis(beta-aminoethyl
      ether) N,N,N',N'-tetrakis(2-benzimidazoyl) (EGTB) was synthesized and fully
      characterized. The complex crystallizes in a monoclinic system with space group
      P2(1)/c, a=10.125(1)A, b=28.393(3)A, c=11.026(1)A, and beta=98.966(2) degrees.
      The hexa-coordinated nickel(II) centers in the centrosymmetric complex adopt a
      distorted octahedron geometry. The complex binds to purine nucleotides covalently
      and shows a clear preference for guanosine-5'-monophosphate (5'-GMP) over
      adenosine-5'-monophosphate (5'-AMP). Its binding to calf thymus DNA (CT-DNA)
      induces a remarkable conformational variation. The cytotoxic activity of the
      complex was tested against diverse cell lines including human leukemic cell line
      U937, macrophage cell line Raw 264.7, human cervical cancer cell line Hela, and
      human hepatocytes cell line L02. The complex shows a significant inhibition
      against U937 and Raw 264.7 but little inhibition against Hela and L02.

PMID- 17540449
TI  - Probing phospholipid dynamics by electrospray ionisation mass spectrometry.
AB  - Recent advances in electrospray ionisation mass spectrometry (ESI-MS) have
      greatly facilitated the analysis of phospholipid molecular species in a growing
      diversity of biological and clinical settings. The combination of ESI-MS and
      metabolic labelling employing substrates labelled with stable isotopes is
      especially exciting, permitting studies of phospholipid synthesis and turnover in
      vivo. This review will first describe the methodology involved and will then
      detail dynamic lipidomic studies that have applied the stable isotope
      incorporation approach. Finally, it will summarise the increasing number of
      studies that have used ESI-MS to characterise structural and signalling
      phospholipid molecular species in development and disease.

PMID- 17540450
TI  - A high pressure liquid chromatography-based assay for glutathione-S-transferase
      class distinction assay.
AB  - In order to expedite the process of classification of the members of the family
      of glutathione-S-transferases (GSTs) high performance liquid chromatography with
      photodiode array detection (HPLC-PDA) was used as a means for measuring enzymatic
      activity. The GST chosen for the development of the HPLC-PDA technique was from
      equine liver (E-GST). The characterizing substrates, ethacrynic acid (EA) and
      bromosulfophthalein (BSP), along with previously gathered characterization data
      allowed for the distinction of alpha, mu or pi-class enzymes. In an initial
      characterization of the previously unclassified E-GST it was determined that the
      enzyme was of the pi-class with specific activities of 0.062, +/-0.0015 micromol
      min(-1) mg(-1) and 0.0019, +/-0.00064 micromol min(-1) mg(-1) for EA and BSP,
      respectively. Finally, the activity of the E-GST with the EA and BSP substrates,
      was measured by HPLC-PDA, and was found to be 0.027, +/-0.003 micromol min(-1)
      mg(-1) and 0.002, +/-0.0005 micromol min(-1) mg(-1), respectively. While the HPLC
      PDA data do not mirror the spectrophotometric results quantitatively the overall
      response by the E-GST was the same. In general, the E-GSTs were shown to belong
      to the pi-class when characterized by HPLC-PDA due to an EA specific activity
      greater than 0.01 micromol min(-1) mg(-1) and a negligible BSP activity (</=0.002
      micromol min(-1) mg(-1)).

PMID- 17540451
TI  - An intron-based real-time PCR method for measuring vasopressin gene
      transcription.
AB  - The hypothalamus contains distinct neuronal populations that express
      distinguishing neuropeptides. The supraoptic nucleus contains magnocellular
      neurons that predominantly express either vasopressin or oxytocin.
      Transcriptional activators of vasopressin and other neuropeptides have been the
      subject of much research. Here we present a method of measuring neuropeptide
      transcription by tailoring one-step quantitative real-time PCR (qRT-PCR) for the
      analysis of processed and pre-mRNA (heteronuclear RNA). Using moderate and strong
      hyperosmotic stimuli to induce transcription, we report an increase in
      vasopressin transcription (pre-mRNA) of 141% and 406% over control levels in
      response to a 2% injection of 900 mOsm saline or a 1% body weight i.p. injection
      of 2 M NaCl, respectively. These results agree with a host of studies employing
      the more labor-intensive method of in situ hybridization histochemistry by which
      investigators also measured intron-containing heteronuclear RNAs. Furthermore,
      these results confirm that qRT-PCR with intron-specific primers can be used to
      rapidly analyze transcription, and suggest an important further benefit of a real
      time PCR analysis, such as the ability of measuring transcription of multiple
      neuropeptides along with other genes from a single sample.

PMID- 17540452
TI  - A CMOS-based microelectrode array for interaction with neuronal cultures.
AB  - We report on the system integration of a CMOS chip that is capable of
      bidirectionally communicating (stimulation and recording) with electrogenic cells
      such as neurons or cardiomyocytes and that is targeted at investigating
      electrical signal propagation within cellular networks in vitro. The overall
      system consists of three major subunits: first, the core component is a 6.5 mm x
      6.5 mm CMOS chip, on top of which the cells are cultured. It features 128
      bidirectional electrodes, each equipped with dedicated analog filters and
      amplification stages and a stimulation buffer. The electrodes are sampled at 20
      kHz with 8-bit resolution. The measured input-referred circuitry noise is 5.9
      microV root mean square (10 Hz to 100 kHz), which allows to reliably detect the
      cell signals ranging from 1 mVpp down to 40 microVpp. Additionally, temperature
      sensors, a digital-to-analog converter for stimulation, and a digital interface
      for data transmission are integrated. Second, there is a reconfigurable logic
      device, which provides chip control, event detection, data buffering and an USB
      interface, capable of processing the 2.56 million samples per second. The third
      element includes software that is running on a standard PC performing data
      capturing, processing, and visualization. Experiments involving the stimulation
      of neurons with two different spatio-temporal patterns and the recording of the
      triggered spiking activity have been carried out. The response patterns have been
      successfully classified (83% correct) with respect to the different stimulation
      patterns. The advantages over current microelectrode arrays, as has been
      demonstrated in the experiments, include the capability to stimulate (voltage
      stimulation, 8 bit, 60 kHz) spatio-temporal patterns on arbitrary sets of
      electrodes and the fast stimulation reset mechanism that allows to record
      neuronal signals on a stimulating electrode 5 ms after stimulation
      (instantaneously on all other electrodes). Other advantages of the overall system
      include the small number of needed electrical connections due to the digital
      interface and the short latency time that allows to initiate a stimulation less
      than 2 ms after the detection of an action potential in closed-loop
      configurations.

PMID- 17540453
TI  - Alterations in the hemodynamic response function in cognitively impaired HIV/AIDS
      subjects.
AB  - Functional magnetic resonance imaging (fMRI) has revealed much about altered CNS
      function in HIV/AIDS. In this study, we compared the blood oxygen level dependent
      hemodynamic response function (BOLD HRF) signal in HIV/AIDS and control subjects
      as a necessary pre-condition for fMRI studies of higher level cognitive function.
      Using event-related fMRI, subjects performed a simple sensory-motor activity
      allowing the measurement of the BOLD HRF in the precentral gyrus. There were no
      significant differences in the HRF when viewed as a function of age, hemisphere,
      or HIV serostatus. However, significant results were found after dividing the
      subjects by NIMH impairment classifications. There were 16 control subjects, 19
      Normal/Asymptomatic Neuropsychological Impairment (ANI), and 11 Minor
      Neurocognitive Disorder (MNCD)/HIV-Associated Dementia (HAD) subjects. The HRF of
      MNCD/HAD subjects did not return to baseline after 16s, suggesting subtle
      alterations in neuronal function, which may affect event-related fMRI studies.

PMID- 17540454
TI  - GDNF in Parkinson's disease: the perils of post-hoc power.
AB  - The practice of performing post-hoc power calculations for studies that do not
      demonstrate statistically significant results has been widely recognized in the
      scientific literature as being unhelpful and potentially misleading. However,
      this practice continues to cause confusion in the interpretation of results from
      clinical trials and other studies. Here, we examine the re-interpretation of a
      recent randomized, double-blind, placebo-controlled study of intraputamenally
      administered GDNF in late-stage Parkinson's disease patients [Hutchinson M,
      Gurney S, Newson R. GDNF in Parkinson disease: an object lesson in the tyranny of
      type II. J Neurosci Methods 2007;163:190-2]. Their main criticism is that the
      study was not large enough to detect clinically worthwhile effects and that the
      observed non-significant result does not contradict the promising results
      observed in two previous, small, open-label studies. We have carefully assessed
      the re-analysis of the data performed by Hutchinson et al. and found their
      conclusions to be flawed, in part because they are based on post-hoc power
      calculations. We have reaffirmed that the confidence interval for the treatment
      effect in the placebo-controlled study of GDNF shows that the trial is capable of
      excluding effects of GDNF of the magnitudes that were observed in the open-label
      studies and that the conclusions drawn in the original paper remain
      scientifically sound.

PMID- 17540456
TI  - Common genetic liability to major depression and posttraumatic stress disorder in
      men.
AB  - BACKGROUND: Major depression (MD) and posttraumatic stress disorder (PTSD) are
      highly comorbid. The degree to which a common genetic liability explains the
      etiology of the MD-PTSD association has not been quantified and has important
      implications for research and prevention. METHODS: This paper presents an
      analysis of data from 6744 members of the Vietnam Era Twin Registry. MD and PTSD
      were assessed using the Diagnostic Interview Schedule-III-R in 1991-92. Bivariate
      twin modeling was conducted to determine the genetic and environmental etiology
      of the MD-PTSD association. RESULTS: The best-fitting model for the MD-PTSD
      association included a substantial genetic correlation (r=.77; 95% CI, .50-1.00)
      and a modest individual-specific environmental correlation (r=.34; 95% CI, .19
      .48). Common genetic liability explained 62.5% of MD-PTSD comorbidity. Genetic
      influences common to MD explained 15% of the total variance in risk for PTSD and
      58% of the genetic variance in PTSD. Individual-specific environmental influences
      common to MD explained only 11% of the individual-specific environmental variance
      in PTSD. LIMITATIONS: Our participants were male Vietnam era veterans and our
      findings may not generalize to civilians, females or other cohorts. CONCLUSIONS:
      MD-PTSD comorbidity is largely explained by common genetic influences.
      Substantial genetic overlap between MD and PTSD implies that genes implicated in
      the etiology of MD are strong candidates for PTSD and vice versa. Environmental
      influences on MD and PTSD explain less of their covariation and appear to be
      largely disorder-specific. Research is needed to identify environmental factors
      that influence the development of MD versus PTSD in the context of common genetic
      liability.

PMID- 17540457
TI  - Dietary L-carnitine supplementation enhances the lipopolysaccharide-induced acute
      phase protein response in broiler chickens.
AB  - The objective of the present study was to evaluate the potential effects of
      dietary L-carnitine supplementation on acute phase protein response upon a
      lipopolysaccharide (LPS) challenge of male broiler chickens receiving a
      commercial broiler diet supplemented with 15 or 100 mg L-carnitine/kg or an
      unsupplemented (control) diet from 14 days of age onwards. At 28 days of age,
      eight chickens per dietary treatment were weighed and subcutaneously injected
      with 300 microg LPS from E. coli (100 microg LPS/ml saline) or 3 ml saline
      (unsupplemented group only). During the next 10 days, blood samples were taken
      repeatedly and analysed for their hemopexin (HX) and alpha-1 acid glycoprotein
      (AGP) levels. Extra dietary L-carnitine did not affect broiler performance. At
      day 1 postinjection, plasma HX and AGP levels were significantly increased in all
      treatment groups. However, the elevations in circulating HX and AGP levels were
      more pronounced in the L-carnitine supplemented chickens, especially in the 100mg
      L-carnitine group. It is concluded that extra L-carnitine in the diet of broiler
      chickens enhances or advances the acute phase protein response. The exact mode of
      action needs to be elucidated but seems to be consistent with a glucocorticoid
      mimicking effect.

PMID- 17540458
TI  - Vibratory source, vocal quality and fundamental frequency following pediatric
      laryngotracheal reconstruction.
AB  - OBJECTIVE: Surgeons who perform pediatric laryngotracheal reconstruction (LTR)
      have traditionally measured outcomes based on successful airway restoration.
      Additional information regarding post-surgical vocal function may help guide
      outcomes toward optimal voice. This investigation documented the relationship
      between the site of vocal tract vibratory source (glottic versus supraglottic
      versus mixed) and vocal function in children following LTR. METHODS: Endoscopic
      evaluation of voice source was completed in 16 participants who had LTR as
      children. Three judges rated vocal quality using the Consensus Auditory
      Perceptual Evaluation of Voice (CAPE-V). Acoustic analysis was completed to
      obtain fundamental frequency and determine the periodicity of the vibratory
      signal. RESULTS: Seven participants were identified to have glottic vibration and
      nine had supraglottic or mixed-source vibration for voice. All participants were
      rated as having some degree of voice disorder. Those who used primarily
      supraglottic/mixed phonation exhibited significantly worse overall severity,
      roughness, and pitch deviance ratings than did those who used primarily glottic
      phonation. Significant differences in strain were also noted; however, poor inter
      rater reliability rating of strain confounded this result. No significant
      differences in breathiness or loudness ratings were exhibited. Periodic vibration
      was observed in 10 of 16 participants (5 of 7 in the glottic group and 5 of 9 in
      the supraglottic/mixed group). Three of the five participants who had periodic
      supraglottic phonation had fundamental frequency measures (F(0)) that were below
      normative ranges, 1 approximated normal, and 1 was above normal range. Two of the
      five participants who had periodic glottic phonation had lower than expected
      F(0)s, 1 was within normal range, and 2 were high. CONCLUSIONS: As observed in
      earlier studies, voices produced with supraglottic phonation were generally less
      acceptable than those with glottic phonation. However, phonation with
      supraglottic structures yielded highly variable voice that may be amenable to
      change. Some children achieved periodic vibration with alternate structures,
      suggesting inherent flexibility and adaptability in the tissues used to make
      sound.

PMID- 17540459
TI  - Excision of nasal dermoids with intracranial extension - anterior small window
      craniotomy approach.
AB  - OBJECTIVE: Dermoid cysts are the most common midline congenital nasal masses and
      may extend intracranially. They commonly become infected, may distort nasal
      growth, and are cosmetically unacceptable. The treatment of nasal dermoids is
      complete surgical excision. Removal of any intracranial extension traditionally
      required a bicoronal incision and frontal craniotomy, with significant associated
      morbidity. This retrospective study describes a new minimally invasive approach
      for excision of the intracranial component of the dermoid. METHODS: We present
      three cases where a brow incision was used. The intracranial part was removed by
      cutting a small window in the frontal bone directly over the dermoid, minimizing
      complications of formal craniotomy. RESULTS: Good access allowing complete
      excision of the dermoid and very low morbidity was achieved in all patients. The
      dura was breached in one patient at operation but this was easily repaired with a
      periosteal patch. All patients recovered quickly and hospital stay was short. The
      resultant scar was cosmetically acceptable. CONCLUSION: The use of a brow
      incision and small window craniotomy is a successful low morbidity technique for
      excision of nasal dermoids with intracranial extension.

PMID- 17540460
TI  - Dimensions of internal jugular veins in Turkish children aged between 0 and 6
      years in resting state and during Valsalva maneuver.
AB  - OBJECTIVE: We aimed to establish the values of the internal jugular vein (IJV)
      sizes in Turkish children aged between 0 and 6 years. METHODS: Ninety-four normal
      children included in this study. All of the children were imaged by
      ultrasonography (USG) at the level of the cricoid cartilage. The maximal antero
      posterior (AP) and transverse (T) diameters of the IJV were measured during
      regular breathing and Valsalva maneuver. RESULTS: The mean transverse diameter of
      the right and left IJV were 8.11+/-3.01 and 7.64+/-2.68 mm in resting state.
      These values changed to 12.57+/-4.34 and 10.82+/-3.80 mm in Valsalva state,
      respectively. The AP diameters were found to be 5.43+/-2.07 for the right and
      5.86+/-4.53 mm for the left IJV at rest. During VM, these values changed to
      8.70+/-2.40 and 8.30+/-2.90 mm for the right and left IJV, respectively. There
      was no significant difference on the evaluation of the relationship between the
      right and left diameters of the IJV. While there were significant differences in
      sizes between the resting and Valsalva states. Also, the T diameter of the right
      IJV during Valsalva state was greater than those of the left. There were
      significant correlations between the diameters of the IJV and the age, weight and
      height of the children. CONCLUSION: The results we obtained in this study may be
      important in an attempt of intravascular intervention to IJV. These values may
      also be important for the comparison with the IJV sizes of the patients who have
      phlebectasia.

PMID- 17540461
TI  - A rapid DNA hybridization assay for the evaluation of antiviral compounds against
      Epstein-Barr virus.
AB  - There is a need for additional therapies for Epstein-Barr virus (EBV) infections,
      but the routine screening of large numbers of potential inhibitors has been
      difficult due to the laborious nature of traditional assays. A new rapid assay
      was developed to evaluate compounds for antiviral activity against this virus
      that is both rapid and robust. Test compounds are added to cultures of Akata
      cells in 96-well plates that have been induced to undergo a lytic infection.
      Viral DNA produced during the infection is transferred to a membrane and
      quantified using a non-radioactive DNA hybridization assay. This assay was
      validated using a set of compounds with known activity against EBV and results
      compared favorably to an established real-time PCR assay. Subsequent experience
      with this assay has confirmed that it offers improved efficiency and robustness
      compared to other assays used routinely to evaluate candidate compounds for
      antiviral activity against EBV.

PMID- 17540462
TI  - Enhanced protective efficacy and reduced viral load of foot-and-mouth disease DNA
      vaccine with co-stimulatory molecules as the molecular adjuvants.
AB  - To improve efficacy of DNA vaccination, various approaches have been developed,
      including the use of plasmid expressing co-stimulatory molecules as molecular
      adjuvants. In this study, we investigated whether co-inoculation of a construct
      expressing either 4-1BBL or OX40L as the molecular adjuvant with FMDV DNA
      vaccine, pcD-VP1, can increase immune responses and protective efficacies.
      Compared to the group immunized with pcD-VP1 alone, the co-inoculation of either
      molecular adjuvant induced a higher ratio of IgG2a/IgG1, higher levels of
      expression of IFN-gamma in CD4(+) and CD8(+) T cells and antigen-specific CTL
      responses, and more importantly provided an enhanced protection against the live
      FMDV challenge in animals. Concurrently, 4-1BBL as the molecular adjuvant
      dramatically reduced the viral loads of FMDV in vivo after the challenge.
      Together, the results demonstrate that co-stimulatory molecules 4-1BBL and OX40L
      can enhance the antigen-specific cell-mediated responses elicited by VP1 DNA
      vaccine and provide an enhanced protective efficacy with the reduced viral loads.

PMID- 17540463
TI  - Involvement of NK1 receptors in metabolic stress markers after the central
      administration of substance P.
AB  - Substance P (SP) is involved in the pathophysiology of several psychiatric
      disorders and is considered a central stress neurotransmitter. Endogenous SP does
      not inhibit the initial extent of the HPA axis response to restraint stress, but
      reduces the duration of the stress suggesting that SP plays an important role in
      the transition between acute and chronic stress. Stress hormones can alter
      metabolic functions in white adipose tissue and liver. The HPA axis is the
      endocrine pathway that promotes lipolysis elevating free fatty acid levels (FFA)
      in blood, besides indirectly causing hyperglycemia. In the present study, changes
      in the blood levels of stress markers in the anxiogenic-like effects of SP, as
      evaluated on the elevated plus-maze (EPM), were studied in adult male rats. Serum
      corticosterone was used as the traditional stress marker, while the plasma FFA
      and glucose were used as alternative anxiety/stress markers. Our findings show:
      (a) elevated corticosterone levels, confirming the aversive situation induced by
      SP (behaviorally assessed in the EPM) and indicating SP as a "chemical" stressor;
      (b) elevated levels of FFA and glucose, indicators of stress-induced mobilization
      of energy substrates, confirming the stressor effect of SP; (c) FFA levels can be
      used as an accurate, sensitive and reliable index of acute stress situations,
      including in the anxiogenic-like effect of SP, with the FFA response being as
      good as corticosterone as a stress marker in this case; (d) NK1 receptors
      involvement in the underlying mechanisms of the behavioral and metabolic effects
      of SP. Finally, our study indicates that some of these physiological variables
      are positively related to the stressor intensity.

PMID- 17540464
TI  - Partial purification and characterization of DNA polymerase beta-like enzyme from
      Plasmodium falciparum.
AB  - DNA polymerases play crucial roles, not only in DNA replication, transcription
      and recombination, but also in DNA repair to maintain the integrity of the cell's
      genome. In Plasmodium falciparum, only three types of DNA polymerases-alpha,
      gamma, and delta have previously been characterized, whereas DNA polymerase beta,
      the major enzyme operating during base excision repair in eukaryotes, has yet to
      be isolated and characterized. In this study, DNA polymerase beta-like activity
      was detected in crude extract of P. falciparum trophozoites. P. falciparum DNA
      polymerase beta-like enzyme was partially purified using fast protein liquid
      chromatography, with a yield of 2.8% and 825-fold purification. The partially
      purified enzyme was highly resistant to aphidicolin and N-ethylmaleimide, as in
      other eukaryotic enzymes, but was also resistant to 2',3'-dideoxythymidine-5'
      triphosphate and to other synthetic nucleoside analogs. The parasite enzyme
      showed low processivity. Using UG mismatch substrate to investigate base excision
      repair, the P. falciparum DNA polymerase beta-like enzyme could repair a patch
      size of 3-5 nucleotides, indicative of involvement in a long patch repair
      pathway, the first evidence of such a property in the DNA polymerase of a malaria
      parasite.

PMID- 17540465
TI  - Genetic exchange and sub-structuring in Theileria annulata populations.
AB  - Tropical theileriosis, caused by the tick-transmitted protozoan Theileria
      annulata, is a major disease of cattle in many regions of the developing world.
      Development and deployment of current and novel control strategies should take
      into account the potential diversity of parasite populations and therefore it is
      important that the nature and basis for this genetic variation is investigated
      and quantified. The recently completed genome sequence of T. annulata provided an
      opportunity to develop a panel of genetic markers for population studies.
      Bioinformatic screening of the genome sequence identified micro- and mini
      satellite loci, which were PCR amplified from a series of diverse parasite stocks
      in order to characterise their polymorphism and determine their species
      specificity. A panel of 10 polymorphic markers was then selected for population
      genetic studies and used to genotype both cloned and uncloned isolates maintained
      as cell lines of T. annulata isolated from different countries. Uncloned isolates
      comprised a multiplicity of genotypes, while cloned isolates showed evidence of a
      single haploid genome. Population genetic analysis revealed a high level of
      genotypic diversity both between and within countries, as measured by the number
      of distinct multilocus genotypes. Based on measures of genetic differentiation
      (F(ST) and Nei's genetic distance), the parasite populations are geographically
      sub-structured and these measurements positively correlate with geographical
      distance. To investigate whether genetic exchange occurs at random and the
      populations are panmictic, the level of linkage disequilibrium was measured using
      the index of association across all loci. Linkage disequilibrium was observed
      when isolates from all countries were treated as a single population but when the
      isolates from Tunisia were analysed separately, linkage equilibrium was observed.

PMID- 17540466
TI  - Bombesin attenuates pre-mRNA splicing of glucocorticoid receptor by regulating
      the expression of serine-arginine protein p30c (SRp30c) in prostate cancer cells.
AB  - Although glucocorticoids are frequently administered to patients with hormone
      refractory prostate cancer, their therapeutic effectiveness is limited by the
      development of glucocorticoid resistance. The molecular mechanisms of
      glucocorticoid resistance are unknown but are believed to involve neuropeptide
      growth factors and cytokines. We examined the functional interaction between
      bombesin and dexamethasone in PC-3 cells and found that bombesin could act as a
      survival factor by interfering with dexamethasone-mediated growth inhibition.
      Because glucocorticoids exert their effects through glucocorticoid receptors
      (GRs), we measured the expression of GR alpha and GR beta isoforms in the
      presence of bombesin. Western blotting and real time PCR revealed bombesin
      induced expression of GR beta, but not GR alpha. Because GR isoforms are
      generated by alternative splicing of a common GR gene, we examined the expression
      of serine-arginine (SR) proteins involved in alternative splicing, and found that
      the expression of SRp30 was induced by bombesin in PC-3 cells. To characterize
      the role of SRp30 in splicing of GR isoforms, siRNAs specific to various SRp30
      isoforms were transfected into PC-3 cells. We found that suppression of SRp30c
      expression by siRNA specifically antagonized bombesin's effect on glucocorticoid
      mediated inhibition of PC cells, suggesting that bombesin-induced expression of
      SRp30c affects GR pre-mRNA splicing, leading to increased GR beta expression and
      contributing to glucocorticoid resistance in PC cells.

PMID- 17540467
TI  - Exploring microbial diversity in volcanic environments: a review of methods in
      DNA extraction.
AB  - The last decade has been marked by a large number of studies focused on
      understanding the distribution of microorganisms in volcanic environments. These
      studies are motivated by the desire to elucidate how the geochemically extreme
      conditions of such environments can influence microbial diversity both on the
      surface and in the subsurface of the Earth. The exploration of microbial
      community diversity has generally not relied on culture-dependent methods, but
      has been carried out using environmental DNA extraction. Because of the large
      diversity of chemically and physically complex samples, extracting DNA from
      volcanic environments is technically challenging. In view of the emerging
      literature, and our own experience in the optimisation of methods for DNA
      extraction from volcanic materials, it is timely to provide a methodological
      comparison. This review highlights and discusses new insights and methods
      published on DNA extraction methods from volcanic samples, considering the
      different volcanic environments. A description of a recent method for DNA
      extraction from basalt and obsidian glass rock samples from Iceland is included.
      Finally, we discuss these approaches in the wider context of modern work to
      understand the microbial diversity of volcanic environments.

PMID- 17540468
TI  - Sensing radiosensitivity of human epidermal stem cells.
AB  - PURPOSE: Radiosensitivity of stem cells is a matter of debate. For mouse somatic
      stem cells, both radiosensitive and radioresistant stem cells have been
      described. By contrast, the response of human stem cells to radiation has been
      poorly studied. As epidermis is a radiosensitive tissue, we evaluated in the
      present work the radiosensitivity of cell populations enriched for epithelial
      stem cells of human epidermis. METHODS AND MATERIALS: The total keratinocyte
      population was enzymatically isolated from normal human skin. We used flow
      cytometry and antibodies against cell surface markers to isolate basal cell
      populations from human foreskin. Cell survival was measured after a dose of 2Gy
      with the XTT assay at 72h after exposure and with a clonogenic assay at 2 weeks.
      Transcriptome analysis using oligonucleotide microarrays was performed to assess
      the genomic cell responses to radiation. RESULTS: Cell sorting based on two
      membrane proteins, alpha6 integrin and the transferrin receptor CD71, allowed
      isolation of keratinocyte populations enriched for the two types of cells found
      in the basal layer of epidermis: stem cells and progenitors. Both the XTT assay
      and the clonogenic assay showed that the stem cells were radioresistant whereas
      the progenitors were radiosensitive. We made the hypothesis that upstream DNA
      damage signalling might be different in the stem cells and used microarray
      technology to test this hypothesis. The stem cells exhibited a much more reduced
      gene response to a dose of 2Gy than the progenitors, as we found that 6% of the
      spotted genes were regulated in the stem cells and 20% in the progenitors. Using
      Ingenuity Pathway Analysis software, we found that radiation exposure induced
      very specific pathways in the stem cells. The most striking responses were the
      repression of a network of genes involved in apoptosis and the induction of a
      network of cytokines and growth factors. CONCLUSION: These results show for the
      first time that keratinocyte populations enriched for stem cells from human
      epidermis are radioresistant. Based on both repressed and induced genes, we found
      that the major response of the irradiated stem cell population was the regulation
      of genes functionally related to cell death, cell survival and apoptosis.

PMID- 17540469
TI  - Language selection in bilinguals: a spatio-temporal analysis of electric brain
      activity.
AB  - Language selection refers to the cognitive mechanism that allows bilinguals to
      communicate in one language or the other and to switch between languages
      depending on the listener. Previous studies suggested that various brain areas
      might be involved in this process. However, the question remains whether language
      selection is achieved through a language-specific mechanism or through a general
      cognitive control process. To address this question, we compared event-related
      potentials (ERPs) induced by language selection and task selection processes
      during image naming. ERPs were collected from bilingual subjects while tested in
      two different contexts: a monolingual task selection context (TSc) where a post
      stimulus cue instructed subjects either to name the image or generate a
      corresponding verb in their first language (L1), and a bilingual language
      selection context (LSc) where the cue indicated to name the image either in the
      first or the second language. By comparing the ERPs induced by the same L1 naming
      as a function of context, we assumed that if the selection processes varied
      across contexts, then electric brain responses should differ rapidly after the
      cue presentation. Our analysis indicated that the first ERP differences
      accounting for the diverging processes involved appeared between approximately
      220 and 300 ms after the cue. The estimation by source localisation of brain
      regions accounting for these differences pointed to an increased activation
      during LSc in the left middle frontal-precentral gyri, supramarginal and angular
      gyri. Our results suggest that language selection is achieved through a neural
      network involving areas implicated in both general cognitive processes and
      language processing.

PMID- 17540470
TI  - Autonomic characteristics of defensive hostility: reactivity and recovery to
      active and passive stressors.
AB  - The autonomic characteristics of hostility and defensiveness were assessed in 55
      male undergraduates based on composite Cook Medley Hostility (Chost) and Marlowe
      Crowne Social Desirability (MC) scores to create 4 groups: Defensive Hostile (DH;
      high MC, high Chost), High Hostile (HH; low MC, high Chost), Defensive (Def; high
      MC, low Chost) and Low Hostile (LH; low MC, low Chost). All subjects engaged in a
      video game (VG) and hand cold pressor (CP) task. Cardiovascular responses in DH
      subjects were predicted to show enhanced sympathetic alpha and beta-adrenergic
      activity and the least vagal control compared to others across tasks. DH and LH
      men showed significant heart rate reactivity to the CP task compared to HH men.
      LH men showed significant reductions in high frequency power (vagal assessment)
      to the tasks compared to HH men. Future studies may employ harassment techniques
      and include the factors of gender and ethnicity in their assessments.

PMID- 17540471
TI  - The relationship between post-prandial plasma glucose and post-challenge plasma
      glucose in Japanese population.
AB  - The relationship between post-prandial plasma glucose (PPG) and post-challenge
      plasma glucose (PCG) within individuals was investigated in Japanese population.
      The oral glucose tolerance test (OGTT) and measurements of PPG 2h after ingestion
      of a standardized rice-based meal (PPG2h), were performed in 4471 middle-aged
      Japanese subjects (2774 men and 1697 women, 50.7+/-8.5 years). There was a loose
      correlation between PPG2h and PCG2h (r=0.327, p<0.001). The diabetes group
      (n=170) showed the highest PPG2h, followed by the IGT group (n=786) and the NGT
      group (n=3414) (p<0.05). At the cutoff point of 140 mg/dl (7.8 mmol/l) for PPG2h,
      specificities were 94.9% for IGT plus diabetes and 92.9% for diabetes, but
      sensitivities were as low as 23.2% for IGT plus diabetes and 44.7% for diabetes.
      The correlation of PPG2h with PCG2h was stronger in the obese group (BMI>or=25
      kg/m2) than in the lean group (BMI<20 kg/m2). We conclude that the correlation
      between PPG2h and PCG2h was significant but not very tight. In evaluating PPG2h,
      if the cutoff point of 140 mg/dl (7.8 mmol/l) for PCG2h is extrapolated, the
      majority of subjects with dysglycemia could be overlooked.

PMID- 17540472
TI  - 'Where is the public health sector?' Public and private sector healthcare
      provision in Madhya Pradesh, India.
AB  - OBJECTIVE: This paper aims to empirically demonstrate the size and composition of
      the private health care sector in one of India's largest provinces, Madhya
      Pradesh. METHODOLOGY: It is based on a field survey of all health care providers
      in Madhya Pradesh (60.4 million in 52,117 villages and 394 towns). Seventy-five
      percent of the population is rural and 37% live below poverty line. This survey
      was done as part of the development of a health management information system.
      FINDINGS: The distribution of health care providers in the province with regard
      to sector of work (public/private), rural-urban location, qualification,
      commercial orientation and institutional set-up are described. Of the 24,807
      qualified doctors mapped in the survey, 18,757 (75.6%) work in the private
      sector. Fifteen thousand one hundred forty-two (80%) of these private physicians
      work in urban areas. The 72.1% (67793) of all qualified paramedical staff work in
      the private sector, mostly in rural areas. CONCLUSION: The paper empirically
      demonstrates the dominant heterogeneous private health sector and the overall the
      disparity in healthcare provision in rural and urban areas. It argues for a new
      role for the public health sector, one of constructive oversight over the entire
      health sector (public and private) balanced with direct provision of services
      where necessary. It emphasizes the need to build strong public private
      partnerships to ensure equitable access to healthcare for all.

PMID- 17540473
TI  - Polymer carriers for drug delivery in tissue engineering.
AB  - Growing demand for tissues and organs for transplantation and the inability to
      meet this need using by autogeneic (from the host) or allogeneic (from the same
      species) sources has led to the rapid development of tissue engineering as an
      alternative. Tissue engineering aims to replace or facilitate the regrowth of
      damaged or diseased tissue by applying a combination of biomaterials, cells and
      bioactive molecules. This review focuses on synthetic polymers that have been
      used for tissue growth scaffold fabrication and their applications in both cell
      and extracellular matrix support and controlling the release of cell growth and
      differentiation supporting drugs.

PMID- 17540474
TI  - Using a smaller plate did not reduce energy intake at meals.
AB  - In three cross-over experiments, we examined the effect on energy intake of
      changing the size of the plate used at a meal. On separate days, adults were
      served the same lunch menu but were given a different-sized plate. In the first
      study, 45 participants used each of three plate sizes (17, 22, or 26 cm) and
      served the main course from a large dish. In the second study, 30 participants
      received an equal amount of food presented on each of the two larger plates. In
      the third study, 44 participants used each of the three plates and selected from
      a buffet of five foods matched for energy density. Results showed that plate size
      had no significant effect on energy intake. The mean differences in intake using
      the smallest and largest plates in the three studies were 21+/-13 g, 11+/-13 g,
      and 4+/-18 g, respectively, equivalent to <142 kJ (34 kcal) and not significantly
      different from zero. Participants in the third study made significantly more
      trips to the buffet when they were given the smallest plate. These findings show
      that using a smaller plate did not lead to a reduction in food intake at meals
      eaten in the laboratory.

PMID- 17540475
TI  - Comparison of the cleaning and disinfecting efficacy of four washer-disinfectors
      for flexible endoscopes.
AB  - Four washer-disinfectors (AdaptaScope, ETD-2Plus, Innova-E3, LS-2000) were
      compared. The cleaning and process efficacies of the washer-disinfectors were
      determined by visible examination and by microbial reduction factor (RF) using
      the German test method (EN ISO/TS 15883-5). Test pieces were contaminated with
      blood and Enterococcus faecium. Three cleaners (Cidezyme GI, ETD Cleaner, Liquid
      52) and three disinfectants (Cidex OPA-C, ETD Disinfectant, Liquid 44) were used.
      The cleaning efficacy was also tested with water alone. Effectiveness of Cidezyme
      GI in the AdaptaScope was determined with an RF of 7.0, in the LS-2000 with an RF
      of 8.4; Liquid 52 obtained in the LS-2000 an RF of 7.0. The cleaning efficacies
      with water for the AdaptaScope (RF 2.1) and the LS-2000 (RF 1.2) were
      significantly different. Microbiological effectiveness of overall processes
      obtained in the AdaptaScope with Cidezyme GI/Cidex OPA-C (RF 8.4) and in the LS
      2000 with Liquid 52/Liquid 44 (RF 9.2) were also significantly different. The
      test pieces remained contaminated at the end of overall processes in the Innova
      E3 and an RF could not be established. In the ETD-2Plus the RFs after the total
      processes were low (3.7-7.5 and 1.8). The AdaptaScope and LS-2000 consistently
      produced a microbial reduction, although differences in the efficacy of the
      overall processes were observed. Processing endoscopes with artificially blocked
      channels in the AdaptaScope and LS-2000 incurred error messages and the processes
      stopped whereas the ETD-2Plus and Innova-E3 did not display error messages.

PMID- 17540476
TI  - Hepatitis B virus DNA in serum of 'anti-HBc only'-positive healthy Lebanese blood
      donors: significance and possible implications.
AB  - Transmission of HBV infection through transfusion of HBsAg-negative blood has
      been documented. It is evident that low levels of HBV-DNA remain detectable in
      serum and liver tissue of some patients who clear HbsAg, and that the detection
      rate is highest in individuals who are 'anti-HBc positive alone'. This study was
      designed to assess the frequency and clinical significance of 'anti-HBc alone' in
      Lebanese blood donors. A total of 5511 blood donor samples from three major
      hospitals representing most regions of the country were tested for anti-HBc,
      amongst other screening tests. Samples positive for 'anti-HBc alone' were then
      tested for HBV-DNA and any positive for HBV-DNA were then genotyped and
      investigated for hepatitis B viral load. The study showed that 203 (3.7%) of
      randomly selected Lebanese blood donors were confirmed as 'anti-HBc alone'. Of
      these, 11 (5.4%) were HBV-DNA positive as detected by nested PCR. All samples had
      HBV-DNA levels below 400 copies/ml and all were genotype D. It can be concluded
      that HBV was present, although the circulating amount of virus was below the
      detectable limit for the assay used. Therefore, routine screening for anti-HBc
      may be required in Lebanese blood donation centres as an additional preventive
      measure for controlling transmission of HBV via blood transfusion.

PMID- 17540477
TI  - Impact of a six-year control programme on surgical site infections in France:
      results of the INCISO surveillance.
AB  - Surgical site infections (SSI) are a key target of nosocomial infection control
      policy. We evaluated the impact of a six-year surveillance system based on data
      from INCISO, a network of volunteer surgical wards from hospitals in Northern
      France. Each year surgical patients were enrolled consecutively and surveyed
      during their in- and out-hospital stay until 30 days following surgery. A
      standardised form was completed for each patient including SSI diagnosis
      according to standard criteria and several risk factors such as wound class,
      American Society of Anesthesiologists score, operation duration,
      elective/emergency, videoscopy and type of surgery. A dashboard was displayed at
      the end of each annual survey, so that participants could compare with other
      surgery adjusted for National Nosocomial Infections Surveillance system (NNIS)
      risk index and standardised incidence ratio (SIR). Over the six years, 3661 SSI
      were identified in 150 440 surgical patients (crude incidence: 2.4%) from 548
      surgery wards. The crude SSI incidence decreased from 3.8 to 1.7% (P for trend
      <0.0001, relative reduction: -55%) and the NNIS-0 adjusted SSI incidence from 2.0
      to 1% (P for trend <0.0001; relative reduction: -50%). An active surveillance
      system striving for benchmark through a network is an effective strategy to
      reduce SSI incidence. Sustaining control efforts have to be made to maintain low
      SSI level beyond the three primer years.

PMID- 17540482
TI  - Synthesis of some novel 2,4-disubstituted thiazoles as possible antimicrobial
      agents.
AB  - A series of novel 4-aryl/chloroalkyl-2-(2,3,5-trichlorophenyl)-1,3-thiazoles (5a
      g and 7a-e) were synthesized by condensing 2,3,5-trichlorobenzenecarbothioamide
      with phenacyl bromide/dichloroacetone. 2,3,5-Trichlorobenzaldehyde
      thiosemicarbazone on treatment with phenacyl bromide afforded 4-aryl-2-(2,3,5
      trichlorophenylidenehydrazino)-1,3-thiazoles (10a-g) in good yield. The newly
      synthesized compounds are characterized by IR, (1)H NMR and mass spectral
      studies. These compounds were also screened for their antibacterial and
      antifungal activities. Preliminary results reveal that some of the synthesized
      compounds are showing promising antimicrobial activity.

PMID- 17540480
TI  - Adipokines and the blood-brain barrier.
AB  - Just as the blood-brain barrier (BBB) is not a static barrier, the adipocytes are
      not inert storage depots. Adipokines are peptides or polypeptides produced by
      white adipose tissue; they play important roles in normal physiology as well as
      in the metabolic syndrome. Adipokines secreted into the circulation can interact
      with the BBB and exert potent CNS effects. The specific transport systems for two
      important adipokines, leptin and tumor necrosis factor alpha, have been
      characterized during the past decade. By contrast, transforming growth factor
      beta-1 and adiponectin do not show specific permeation across the BBB, but
      modulate endothelial functions. Still others, like interleukin-6, may reach the
      brain but are rapidly degraded. This review summarizes current knowledge and
      recent findings of the rapidly growing family of adipokines and their
      interactions with the BBB.

PMID- 17540481
TI  - C-reactive protein and rate of dementia in carriers and non carriers of
      Apolipoprotein APOE4 genotype.
AB  - BACKGROUND: Those with an Apolipoprotein APOE4 allele (APOE4) have lower C
      reactive protein (CRP) than those without APOE4. Whether APOE4 modifies the
      effects of CRP on rate of all cause dementia, cognitive impairment or Alzheimer's
      disease (AD) is not established. METHODS: All cause dementia and cognitive
      impairment without dementia (CIND) was determined over five follow up visits from
      1998 to 2006 in an ongoing cohort of older Latinos. The association between high
      sensitivity CRP and dementia/CIND, all cause dementia and Alzheimer's disease by
      APOE4 status was examined in semi-parametric survival models with covariate
      adjustments. RESULTS: CRP was significantly lower among those with APOE4 than in
      those without. Among those with APOE4, CRP was associated with lower rates of
      combined dementia/CIND (HR: 0.60, 95% CL: 0.20-0.91, p=0.03) from a fully
      adjusted model. Among those with no APOE4, there was no effect of CRP on
      dementia/CIND rates (HR: 0.94, 95% CL: 0.67-1.33). CONCLUSIONS: Lower CRP in
      those with APOE4 may reflect immune effects of the APOE4 genotype. Higher CRP in
      those with APOE4 may be a marker of better immune function, leading to lower rate
      of dementia and AD.

PMID- 17540483
TI  - Cloning of full length genome of varicella-zoster virus vaccine strain into a
      bacterial artificial chromosome and reconstitution of infectious virus.
AB  - The complete genome of the varicella-zoster virus (VZV) Oka vaccine strain (vOka)
      has been cloned into a bacterial artificial chromosome (BAC), and several BAC
      clones with the vOka genome have been obtained. Infectious viruses were
      reconstituted in MRC-5 cells transfected with the vOka-BAC DNA clones. The clones
      were distributed into two groups based on differences in amino acids found in ORF
      62/71 region among the vOka-BAC clones. The recombinant vOka (rvOka) grew slower
      than recombinant Oka parental virus (rpOka), pOka and vOka. This is the first
      report that the vOka genome was cloned into BAC vector. The rvOka-BAC system
      would be useful as a vector for construction of recombinant live vaccines.

PMID- 17540484
TI  - Progressive vaccinia as an adverse event following exposure to vaccinia virus:
      case definition and guidelines of data collection, analysis, and presentation of
      immunization safety data.

PMID- 17540485
TI  - Abscess at injection site: case definition and guidelines for collection,
      analysis, and presentation of immunization safety data.

PMID- 17540486
TI  - Nickel sulfate induces numerous defects in Caenorhabditis elegans that can also
      be transferred to progeny.
AB  - Whether the multiple biological toxicities from nickel exposure could be
      transferred to progeny has not been clarified. In this report, we explored the
      Caenorhabditis elegans to analyze the multiple toxicities of nickel and their
      possibly transferable properties. The nickel toxicity caused multiple biological
      defects in a concentration-dependent manner. Moreover, most of these toxicities
      could be transferred and could be only partially rescued in progeny. Some
      specific phenotypes in progeny were also found to exhibit no obvious rescue
      phenotypes or to show even more severe defects than their parents. The defects
      caused by nickel exposure could be classified into four groups according to their
      transferring properties. That is, the defects caused by nickel exposure could be
      largely, or partially, or unable to be rescued, or became even more severe in
      progeny animals. Therefore, most of the nickel exposure-caused defects can be
      transferred from parents to their progeny to different degrees in C. elegans.

PMID- 17540487
TI  - Use of principal component analysis to profile temporal and spatial variations of
      chlorinated solvent concentration in groundwater.
AB  - This work aims at evaluating spatial distribution patterns of concentration
      variations for chlorinated solvents in groundwater, based on principal component
      analysis and geographic information system (GIS) tools. The study investigates
      long-time series of chlorinated solvent concentrations in groundwater measured
      for 18 contaminated industrial sites. The characterization of contaminant plumes
      and delineation of pollutant sources are essential for choosing appropriate
      monitoring and remediation strategies, as contaminated groundwaters are
      characterized by complex patterns of spatial and temporal concentration
      variability, with wide unpredictable fluctuations over time. The present work
      describes the results of a new exploratory statistical method called the
      Variability Index Method (VIM) applied to environmental data to assess the
      performance of using concentration variations as molecular tracers to reveal
      aquifer dynamics, industrial impacts, and point sources for contamination plumes.
      The application of this method provides a useful assessment of controls over
      contaminant concentration variations as well as support for remediation
      techniques.

PMID- 17540488
TI  - Children's health and the social theory of risk: insights from the British
      measles, mumps and rubella (MMR) controversy.
AB  - Recent debates in the United Kingdom about the measles, mumps and rubella (MMR)
      vaccine and its alleged link with autism have centred on contested notions of
      risk. This paper presents findings from 87 parents' focus group and interview
      discussions of their decision-making about the vaccine in light of three streams
      of theoretical literature on risk (cultural theory, risk society, psychometric
      models of risk perception) and models of vaccination acceptance and resistance.
      In addition to the risks of infectious disease and autism, parents balanced other
      risk concerns-both biological and social-in making their decisions. Such
      decisions, made on behalf of children unable to choose for themselves, and in the
      midst of contradictory information and uncertainty, symbolised what it means to
      be a 'good parent'. To cope with uncertainty, parents sought explanations for why
      some children seem to be more vulnerable to adverse outcomes than others. Debates
      about children's risks may need special theoretical consideration beyond that
      offered by the current risk literature. Specific aspects of the MMR debate,
      namely, selecting between potentially competing risks, making risk judgements on
      behalf of dependent others, and tensions between private and public good, provide
      a platform for exploring how social theories of risk might be adapted for
      children's health controversies.

PMID- 17540489
TI  - Response preparation with static versus moving hands.
AB  - This research tested the response inhibition account of the hand-advantage found
      in the finger pre-cuing task. According to this account, the advantage of
      preparing two fingers on one hand (represented in one hemisphere) as opposed to
      preparing two fingers on two hands (represented in two hemispheres) is due, in
      part, to a response inhibition process that operates more efficiently within than
      between hemispheres. In this view, supplying extra activation to both hemispheres
      by moving the hands should decrease the within-hemisphere inhibition advantage.
      Twelve participants performed the finger pre-cuing task with static and moving
      hands. As predicted by the response inhibition account, the hand-advantage,
      present with the hands at rest, decreased with the hands moving.

PMID- 17540490
TI  - Poisoning by mad honey: a brief review.
AB  - Several plants of the Ericaceae family produce grayanotoxins which can poison
      humans. The best-known of these intoxications involves the eating of 'mad honey
      (deli bal in Turkish)' contaminated by Rhododendron nectar grayanotoxins.
      Accounts of mad honey intoxication date back to 401 BC. It is still one of the
      common food intoxications encountered for humans and livestock in Turkey. Mad
      honey intoxication's symptoms are dose-related. In mild form, dizziness,
      weakness, excessive perspiration, hypersalivation, nausea, vomiting and
      paresthesias are present and close follow-up is enough. However, severe
      intoxication may lead to life threatening cardiac complications such as complete
      atrioventricular block that can be treated intravenously. In this review,
      properties and sources of grayanotoxins, their detection methods and mad honey
      intoxication are discussed.

PMID- 17540491
TI  - Effect of milk on the 7,12-dimethylbenz[a]-anthracene-induced mammary tumor model
      in rat.
AB  - Milk may be one of the risk factors in the development of breast cancer from
      epidemiological investigations. Our study investigated the hormones and main
      ingredients in milk and assessed the effects of milk on the development of 7,12
      dimethylbenz(a)anthracene (DMBA)-induced mammary tumors in rats by comparing
      differences among three groups: commercial milk (C), traditional milk (T) or
      water (W). During the 20-weeks experiment the C and T groups showed higher
      incidences of mammary tumors than the W group. After excluding potential
      confounding factors including fat and calcium, the C group was found to score
      higher than the T group in the indices of tumorigenesis. These findings suggested
      that DMBA-induced mammary tumors are more prevalent in milk-fed groups due in
      part to the contribution of estrogen and progesterone in milk.

PMID- 17540492
TI  - Onium salt improves the polymerization kinetics in an experimental dental
      adhesive resin.
AB  - The aim of this study was to evaluate the influence of an onium salt in the
      polymerization kinetics of a dental adhesive model resin. A monomer mixture,
      based on Bis-GMA, TEGDMA and HEMA, was used as a model dental adhesive resin,
      which was polymerized using camphorquinone (CQ) as a photo-initiator in addition
      to either binary or ternary photo-initiator systems. The binary systems were
      formulated with different concentrations of diphenyliodonium hexafluorphosphate
      or ethyl 4-dimethylaminobenzoate in relation to the monomer and 1mol% of CQ. The
      ternary system was a blend of 1mol% of CQ, 2mol% of ethyl 4-dimethylamino
      benzoate and 0.25, 0.5, 1, 2 or 4mol% of onium salt. Real time Fourier Transform
      infrared spectroscopy was used to investigate the polymerization reaction over
      the photo-activation time. When CQ was used as photo-initiator, a slow
      polymerization reaction was observed and a lower monomer conversion. The addition
      of a second component (onium salt or amine) increases the polymerization rate and
      conversion independent on the co-initiator concentration. Ternary photo-initiator
      system showed an improvement on the polymerization rate of the dental adhesive
      model resin leading to high conversion in short photo-activation time. Also, a
      mechanism for initiating polymerization using an amine or onium salt as a co
      initiator component is proposed.

PMID- 17540493
TI  - Accuracy of the LifeShirt (Vivometrics) in the detection of cardiac rhythms.
AB  - The use of heart rate measures in research requires accurate detection and timing
      of beat-to-beat values. Numerous technologies are available to researchers;
      however, benchmarking of a specific apparatus is seldom conducted. Since heart
      rate variability provides a portal to the neural regulation of the heart,
      accurate detection and timing of beat-to-beat values is essential to both basic
      physiological research and the clinical application of heart rate variability
      measures. The current study evaluated the accuracy of an ambulatory system, the
      LifeShirt (Vivometrics), relative to a standard laboratory-based heart rate
      monitoring equipment (Biopac), during baseline and exercise conditions. LifeShirt
      performed equivalently to the Biopac during both conditions, experienced few
      errors of detection, generated similar times between sequential heart periods,
      and produced similar summary indices of heart rate and heart rate variability.

PMID- 17540494
TI  - Twenty-minute pad test: comparison of infusion of 250 ml of water with strong
      desire amount in the bladder in women with stress urinary incontinence.
AB  - OBJECTIVE: The objective was to compare the sensitivity of the 20-min pad test by
      infusion of 250 ml of water with the strong-desire amount in the bladder in women
      with stress urinary incontinence (SUI). STUDY DESIGN: Eighty-three women with SUI
      were enrolled between November 2005 and January 2006. The 20-min pad test by
      infusion of 250 ml of water was performed before urodynamic study (UDS). The
      strong-desire amount pad test was done after UDS. The results were analyzed by
      Pearson's chi(2) and Wilcoxon's signed-rank tests. RESULTS: The sensitivity by
      infusion of the strong-desire amount was better than infusion of 250 ml of water
      in the 20-min pad test (P<0.001). In the quantitative study, the two pad tests
      had fair agreement and the pad weight results of the infusion of the strong
      desire amount were statistically higher than the infusion of 250 ml of water
      (P=0.0004). CONCLUSIONS: The infusion of the strong-desire amount had better
      sensitivity measured by the 20-min pad test in women with SUI compared with
      infusion of 250 ml of water in the bladder.

PMID- 17540495
TI  - How safe is germinal vesicle stage oocyte rescue? Aneuploidy analysis of in vitro
      matured oocytes.
AB  - OBJECTIVE: To evaluate the rate and type of aneuploidies of chromosomes 13, 16,
      18, 21 and 22, with respect to the length of in vitro maturation (IVM) period,
      and to compare the results to previously published studies on aneuploidy rates of
      unfertilized, uninseminated mature oocytes and first polar bodies. STUDY DESIGN:
      Two hundred and twelve immature germinal vesicle stage oocytes were assigned to
      two groups. After successful IVM, depending on their maturational period of 24h
      (Group A) or 36h (Group B), chromosomal analysis was performed by five color
      fluorescence in situ hybridization (FISH). In Groups A and B the rates of
      aneuploid oocytes were calculated and compared by chi-square test. Also the rates
      of hyperhaploidy, hypohaploidy, disomy and nullisomy were determined and compared
      by chi-square test. The difference was considered statistically significant at p
      value of <0.05. RESULTS: The prolonged IVM did not significantly affect the
      aneuploidy rate compared to the shorter maturation period (48.1% and 45.0%,
      respectively). Regarding the unbalanced premature chromatid separation, no
      statistically significant difference was found between hyperhaploidy and
      hypohaploidy (14.8% versus 8.3%). For chromosome nondisjunction, higher frequency
      of disomy than nullisomy was observed (30.6% versus 14.8%; p<0.05). The estimated
      global aneuploidy rate was between 42% and 63%. CONCLUSIONS: The aneuploidy rate
      of IVM GV-oocytes is comparable to the aneuploidy rate of in vivo matured oocytes
      and first polar bodies, regardless of the length of maturation period. This
      suggests that the immature oocytes can be used in infertility treatment after
      they complete maturation.

PMID- 17540496
TI  - Complex-type-dependent scoring functions in protein-protein docking.
AB  - A major challenge in the field of protein-protein docking is to discriminate
      between the many wrong and few near-native conformations, i.e. scoring. Here, we
      introduce combinatorial complex-type-dependent scoring functions for different
      types of protein-protein complexes, protease/inhibitor, antibody/antigen,
      enzyme/inhibitor and others. The scoring functions incorporate both physical and
      knowledge-based potentials, i.e. atomic contact energy (ACE), the residue pair
      potential (RP), electrostatic and van der Waals' interactions. For different type
      complexes, the weights of the scoring functions were optimized by the multiple
      linear regression method, in which only top 300 structures with ligand root mean
      square deviation (L_RMSD) less than 20 A from the bound (co-crystallized) docking
      of 57 complexes were used to construct a training set. We employed the bound
      docking studies to examine the quality of the scoring function, and also extend
      to the unbound (separately crystallized) docking studies and extra 8 protein
      protein complexes. In bound docking of the 57 cases, the first hits of
      protease/inhibitor cases are all ranked in the top 5. For the cases of
      antibody/antigen, enzyme/inhibitor and others, there are 17/19, 5/6 and 13/15
      cases with the first hits ranked in the top 10, respectively. In unbound docking
      studies, the first hits of 9/17 protease/inhibitor, 6/19 antibody/antigen, 1/6
      enzyme/inhibitor and 6/15 others' complexes are ranked in the top 10.
      Additionally, for the extra 8 cases, the first hits of the two protease/inhibitor
      cases are ranked in the top for the bound and unbound test. For the two
      enzyme/inhibitor cases, the first hits are ranked 1st for bound test, and the
      119th and 17th for the unbound test. For the others, the ranks of the first hits
      are the 1st for the bound test and the 12th for the 1WQ1 unbound test. To some
      extent, the results validated our divide-and-conquer strategy in the docking
      study, which might hopefully shed light on the prediction of protein-protein
      interactions.

PMID- 17540497
TI  - Ca2+ and Mg2+ bind tetracycline with distinct stoichiometries and linked
      deprotonation.
AB  - Tetracycline depends on divalent metal ions for its biological function, but its
      multiple ionization states, conformations, and tautomers at varying solution
      conditions complicate its ion-binding equilibria, and the stoichiometry of the
      biologically relevant Ca2+ or Mg2+ complexes has not been clear. Isothermal
      titration calorimetry was used in the present work to study Ca2+ and Mg2+ binding
      to tetracycline. The two metal ions bind with distinct stoichiometries, one Ca2+
      per tetracycline and one Mg2+ per two tetracyclines, and with differing
      dependence on solution conditions, indicating that these two ions bind TC
      differently. An endothermic process accompanies ion binding that is proposed to
      reflect conformational changes in tetracycline. The results identify conditions
      that limit the distribution of species and may facilitate structural study.

PMID- 17540498
TI  - Dialogue and causality: global description from local observations and vague
      communications.
AB  - We propose a dialogue-based society model which explains how the transitive law
      of the causality is originated. Causality is, in general, formalized by using
      axiomatic approaches. Instead of using axiomatic methods, we, however, compose a
      model consisting of agents who have knowledge about causal relations among
      objects. The model society can reveal the transitive law through interactional
      dialogues among themselves. The agents are reciprocally influenced, if they have
      either completely same opinions, or a particular pattern of opinions, that are
      regarded as the extension of such exact accordance. In addition, we add some
      vagueness to the dialogue, which is closer to a real communication than the
      former model. A set of knowledge of each agent is expressed as a directed graph,
      hence the every model can be construed as mere transformations of directed graphs
      through the interactions among directed graphs themselves. Following this
      perspective, the models are the systems that connect local logic with global one,
      while the union of the directed graphs is regarded as the global.

PMID- 17540499
TI  - Photocatalytic degradation of Azure and Sudan dyes using nano TiO2.
AB  - The present study investigates the dependence of photocatalytic rate on molecular
      structure of the substrate that is degraded. The photocatalytic degradation of
      Azure (A and B) and Sudan (III and IV) dyes, having similar structure, but
      different functional groups, were investigated with two catalysts. The
      photocatalytic activity of solution combustion synthesized TiO(2) (CS TiO(2)) was
      compared with that of Degussa P-25 for degrading these dyes. The effect of
      solvents and mixed-solvent system on photodegradation of Sudan III was
      investigated. The photodegradation rate was found to be higher in solvents with
      higher polarity. The effect of pH and the presence of metal ions in the form of
      chloride and nitrate salt, on degradation rate of Azure A was also investigated.
      The metal ions significantly reduced the photocatalysis rates. A detailed
      Langmuir-Hinshelwood kinetic model has been developed to explain the effect of
      metal ions on degradation rate of the substrate. This model elucidates the
      contribution of holes and electrons towards degradation of the dye.

PMID- 17540500
TI  - Dicofol application resulted in high DDTs residue in cotton fields from northern
      Jiangsu province, China.
AB  - Dicofol with high impurity of DDT compounds is still widely used in agricultural
      practice such as cotton cultivation and becomes an important source of DDT
      pollution in China. In this study, investigations on the DDT residues in cotton
      fields from northern Jiangsu province, China were conducted. The results showed
      that DDTs in cotton soil were much higher than other mode of land use. The DDTs
      levels ranged from 4.2 to 678.6 ngg(-1), with a mean concentration of 190.4 ngg(
      1), of which the most abundant compounds were p,p'-DDE (mean of 129.38 ngg(-1)),
      p,p'-DDT (mean of 26.57 ngg(-1)) and o,p'-DDT (mean of 16.92 ngg(-1)). The
      concentrations of o,p'-DDT and o,p'-DDE were significantly higher (p<0.05) in
      topsoil (0-10 cm) than in subsoil (10-20 cm), while other DDT compounds were not.
      Source apportionment showed that dicofol-type DDT accounted for up to 80% of the
      DDTs residue. All the results indicated that dicofol applications resulted in
      serious DDT pollution in cotton fields. Our work provided implications for
      reasons why there was no apparent decrease of DDT level in China.

PMID- 17540501
TI  - High temperature ablation of kaolinite layered silicate/phenolic resin/asbestos
      cloth nanocomposite.
AB  - The successful return of re-entry space vehicle, which is subjected to severe
      aerodynamic heating, is largely accompanied by some provisions to reduce the heat
      transfer to the structure. Heat shield is the best protection means which
      undergoes physical, chemical, and mostly endothermal transformations. The
      objective of this work is to investigate the ablating, charring, and thermal
      degradation behaviour of heat shield resol-type phenolic resin/kaolinite/asbestos
      cloth nanocomposite by oxyacetylene flame test with an external heat flux of 8 x
      10(9)W/m(2) and 3000 K hot gas temperature and thermal analyzer techniques.
      Kinetic parameters of thermal degradation and temperature distribution at the
      back surface of the nanocomposite heat shield were determined and compared with
      that of composite counterpart.

PMID- 17540502
TI  - Photoinduced hydroxyl radical and photocatalytic activity of samarium-doped
      TiO(2) nanocrystalline.
AB  - Sm(3+)-doped TiO(2) nanocrystalline has been prepared by sol-gel auto-combustion
      technique and characterized by X-ray diffraction (XRD), Brunauer-Emmett-Teller
      (BET) method, and also UV-vis diffuse reflectance spectroscopy (DRS). These
      Sm(3+)-doped TiO(2) samples were tested for methylene blue (MB) decomposition and
      *OH radical formation. The analysis of *OH radical formation on the sample
      surface under UV irradiation was performed by fluorescence technique with using
      terephthalic acid, which readily reacted with *OH radical to produce highly
      fluorescent product, 2-hydroxyterephthalic acid. It was observed that the
      presence of Sm(3+) ion as a dopant significantly enhanced the photocatalytic
      activity for MB degradation under UV light irradiation because both the larger
      specific surface area and the greater the formation rate of *OH radical were
      simultaneously obtained for Sm(3+)-doped TiO(2) nanocrystalline. The adsorption
      experimental demonstrated that Sm(3+)-TiO(2) had a higher MB adsorption capacity
      than undoped TiO(2) and the adsorption capacity of MB increased with the increase
      of samarium ion content. The results also indicated that the greater the
      formation rate of *OH radical was, the higher photocatalytic activity was
      achieved. In this study, the optimum amount of Sm(3+) doping was 0.5 mol%, at
      which the recombination of photo-induced electrons and holes could be effectively
      inhibited, the highest formation rate of *OH radicals was, and thereby the
      highest photocatalytic activity was achieved.

PMID- 17540503
TI  - Thermodynamic analysis of the selective carbothermic reduction of electric arc
      furnace dust.
AB  - Electric arc furnace (EAF) dust, which is produced as a result of the melting of
      automobile scrap in an electric arc furnace, contains considerable amounts of
      zinc and lead, which are of significant economic value. Typically, the other
      major components are iron oxide and calcium oxide with minor amounts of other
      metal oxides. In this research, a detailed thermodynamic study of the
      pyrometallurgical processing of the dust, using carbon as a reducing agent was
      performed. The SOLGASMIX solver of Outokumpu HSC Chemistry((R)) 5.1 was used to
      calculate the equilibrium composition under reducing conditions. The control
      input dust composition was as follows (in mass percent): 8.100% CaO, 8.250%
      2CaO.SiO(2), 11.200% CaCO(3), 8.830% CaO.Fe(2)O(3), 7.840% Fe(3)O(4), 3.770% PbO,
      38.150% ZnFe(2)O(4) and 13.860% ZnO. Selective reduction and separation of both
      the zinc and the lead as metallic vapours, from the iron, in oxide form, was
      examined. The separation of the zinc or the lead from the iron, was defined
      quantitatively in terms of the selectivity factor (logbeta) as follows. Equation
      [see the text] where the subscript symbols refer to the metal being present in
      gaseous (g), metallic solid (m), solid oxide (o) or metallic liquid (l) form,
      respectively. The standard calculations were performed for one hundred grams of
      dust at atmospheric pressure. The variables investigated were as follows;
      temperature in the range of 1273-1873K, reactant ratio (i.e. moles of carbon per
      gram of dust), dust composition, addition of inert gas and reduced total
      pressure. The calculated values were in reasonable agreement with those from
      previously published studies and also industrial results.

PMID- 17540504
TI  - Sulfamethoxazole abatement by photo-Fenton toxicity, inhibition and
      biodegradability assessment of intermediates.
AB  - The objective of this work was to study the abatement of 200mgL(-1)
      sulfamethoxazole (SMX) solution by means of photo-Fenton process.
      Biodegradability of the treated solutions was followed by the ratio biochemical
      oxygen demand at five days/chemical oxygen demand (BOD(5)/COD) and toxicity by
      Microtox and inhibition tests. Experiments with different initial concentration
      of H(2)O(2) were carried out. The initial amount of Fe(2+) and pH of the solution
      were set at 10mgL(-1) and 2.8 respectively. The temperature of the reactor was
      kept constant in all the experiments (25+/-0.8 degrees C). Photo-Fenton process
      is thought to be a successful treatment step to improve the biodegradability of
      wastewater containing SMX. The complete antibiotic removal was achieved for a
      H(2)O(2) dose over 300mgL(-1). Biodegradability (BOD(5)/COD) rose from zero (SMX
      solution) to values higher than 0.3 (treated solutions). Toxicity and inhibition
      tests pointed out in the same direction: oxidized intermediates for initial
      H(2)O(2) dose over 300mgL(-1) showed no toxicity effects on pure bacteria and no
      inhibition on activated sludge activity.

PMID- 17540505
TI  - Mice lacking L1 have reduced CGRP fibre in-growth into spinal transection
      lesions.
AB  - Repair strategies for spinal cord injury often focus on promoting regeneration of
      injured axons and stimulating subsequent functional recovery. Although many of
      these strategies have proven their merits, less is known about potential unwanted
      side-effects, such as sprouting of nociceptive CGRP immunoreactive axons, which
      may bring about pain-related behavior. Sprouting of CGRP axons into lesion sites
      spontaneously occurs after spinal cord injury (SCI). Using L1-deficient mice we
      show a reduction of such CGRP growth response. This reduction was specific for
      CGRP axons since the overall neurofilament positive fibre in-growth into the
      spinal lesion site was not affected. Our results may have important implications
      on the development and assessment of repair strategies that should not only
      stimulate functional recovery, but also prevent the development of pain or
      autonomic dysreflexia.

PMID- 17540506
TI  - A rapid inhibition of NMDA receptor current by corticosterone in cultured
      hippocampal neurons.
AB  - The stress level of corticosterone (CORT) may enhance the vulnerability of
      neurons to insult by increasing N-methyl-D-aspartate (NMDA) receptor activity. In
      this study, we present data showing that CORT could exert an inhibitory effect on
      NMDA currents in cultured neonatal hippocampal neurons. Extracellular application
      of 0.1,1,10 and 100 microM CORT significantly reduced the inward current evoked
      by co-application of NMDA (100 microM). Extracellular application of a membrane
      impermeable CORT-BSA (10 microM) maintained the CORT effect. RU38486 (10 microM)
      failed to block the CORT (1 microM) inhibitory effect. Additionally,
      intracellular application of CORT (10 microM) showing the lack of effectiveness
      indicated that a non-genomic mechanism mediated the CORT suppression on NMDA
      receptors in hippocampal neurons. Furthermore, to elevate the activity of protein
      kinase A by intracellular 8-Br-cAMP maintained the suppressive effect of CORT on
      NMDA current. Intracellular blockade of protein kinase A by Rp-cAMP (10 microM)
      or staurosporine (50 nM) reduced NMDA currents and abolished CORT depression of
      NMDA currents. These data indicated that NMDA current itself is dependent on
      protein kinase A (PKA) activity and CORT depression of the current could be PKA
      dependent at the same time. The rapid inhibitory effect of the stress level CORT
      on NMDA current might suggest a protective mechanism for neurons exposed to a
      transient increase in glucocorticoids.

PMID- 17540507
TI  - Reorganization of receptive fields following hearing loss in inferior colliculus
      neurons.
AB  - We explored frequency and intensity encoding in the inferior colliculus (IC) of
      the C57 mouse model of sensorineural hearing loss. Consistent with plasticity
      reported in the IC of other models of hearing loss, frequency response areas
      (FRAs) in hearing-impaired (HI) mice were broader with fewer high-frequency units
      than normal-hearing (NH) mice. The broad FRAs recorded from HI mice had lower
      cutoffs on the low frequency edge of the FRA. Characteristic frequency (CF) and
      sharpness of tuning (Q10) calculated from the FRA were used to divide the sample
      into four categories: low-CF sharp-FRA, low-CF broad-FRA, high-CF sharp-FRA, and
      high-CF broad-FRA units. Rate-intensity functions (RIFs) for CF tones and noise
      were used to determine the minimum and maximum response counts as well as the
      sound pressure levels resulting in 10%, 50%, and 90% of the maximum spike count.
      Tone RIFs of broad FRA units were shifted to the right of tone RIFs of sharp FRA
      units in both NH and HI mouse IC, regardless of the unit CF. The main effects of
      hearing loss were seen in the noise RIFs. The low-CF broad-FRA units in HI mice
      had elevated responses to noise, and the high-CF sharp-FRA units in HI mice had
      lower maximum rates, as compared with the units recorded from NH mice. These
      results suggest that, as the IC responds to peripheral hearing loss with changes
      in the representation of frequency, an altered balance between inhibitory and
      excitatory inputs to the neurons recorded from the HI mice alters aspects of the
      units' intensity encoding. This altered balance likely occurs, at least in part,
      outside of the IC.

PMID- 17540509
TI  - Histological diversity of reactive and atypical proliferative lymph node lesions
      in systemic lupus erythematosus patients.
AB  - Localized or generalized lymphadenopathy, which may be associated with systemic
      symptoms such as fever, is frequently found in patients with systemic lupus
      erythematosus (SLE). Histologically, the lymph node lesion is characterized by
      varying degrees of coagulative necrosis with hematoxylin bodies or reactive
      follicular hyperplasia. The former histology is unique to SLE, but is rarely seen
      in biopsied specimens. In this review, we describe a histologic variation of SLE
      lymphadenopathy based on the findings of our own cases, and discuss several
      problems related to the differential diagnosis of various benign and malignant
      lymphoproliferative disorders (LPDs). Among 33 cases we encountered, 17 (51%)
      cases exhibited atypical LPDs: (i) reactive follicular hyperplasia with giant
      follicles (RFHGFs), 3 cases; (ii) histologic findings of Castleman's disease
      (CD), 5 cases ; (iii) atypical paracortical hyperplasia with lymphoid follicles
      (APHLFs), 7 cases; and (iv) atypical lymphoplasmacytic and immunoblastic
      proliferation (ALPIBP), 2 cases. This finding indicates that atypical LPDs
      frequently appear in SLE. Moreover, the majority of patients with atypical LPDs
      exhibited follicular hyperplasia (RFHGF, 3 cases; histologic findings of CD, 5
      cases; and APHLF, 7 cases). Previously, follicular hyperplasia was usually
      considered a non-specific change and therefore has received little attention in
      the literature. However, the present review indicates that reactive follicular
      hyperplasia in lymph nodes from SLE occasionally poses serious problems in the
      differential diagnosis of various benign and malignant LPDs. The presence of
      numerous copies of Epstein-Barr virus was determined by in situ hybridization
      studies in only two (8%) of the 26 cases examined. As previously suggested, the
      absence of EBV, as determined by ISH studies, in the majority of LPDs associated
      with SLE indicates that EBV is not related to the lymphoproliferative process,
      and suggests that the underlying cause of the patient's lymphadenopathy may
      reside in the immune deficit of SLE in the majority of reactive and atypical LPDs
      associated with SLE.

PMID- 17540508
TI  - Morphine preferentially activates the periaqueductal gray-rostral ventromedial
      medullary pathway in the male rat: a potential mechanism for sex differences in
      antinociception.
AB  - The midbrain periaqueductal gray (PAG), and its descending projections to the
      rostral ventromedial medulla (RVM), provide an essential neural circuit for
      opioid-produced antinociception. Recent anatomical studies have reported that the
      projections from the PAG to the RVM are sexually dimorphic and that systemic
      administration of morphine significantly suppresses pain-induced activation of
      the PAG in male but not female rats. Given that morphine antinociception is
      produced in part by disinhibition of PAG output neurons, it is hypothesized that
      a differential activation of PAG output neurons mediates the sexually dimorphic
      actions of morphine. The present study examined systemic morphine-induced
      activation of PAG-RVM neurons in the absence of pain. The retrograde tracer
      Fluorogold (FG) was injected into the RVM to label PAG-RVM output neurons.
      Activation of PAG neurons was determined by quantifying the number of Fos
      positive neurons 1 h following systemic morphine administration (4.5 mg/kg).
      Morphine produced comparable activation of the PAG in both male and female rats,
      with no significant differences in either the quantitative or qualitative
      distribution of Fos. While microinjection of FG into the RVM labeled
      significantly more PAG output neurons in female rats than male rats, very few of
      these neurons (20%) were activated by systemic morphine administration in
      comparison to males (50%). The absolute number of PAG-RVM neurons activated by
      morphine was also greater in males. These data demonstrate widespread
      disinhibition of PAG neurons following morphine administration. The greater
      morphine-induced activation of PAG output neurons in male compared with female
      rats is consistent with the greater morphine-induced antinociception observed in
      males.

PMID- 17540510
TI  - Disease-specific expression patterns of proteases in synovial tissues.
AB  - To assess whether protease expression patterns can be discriminated according to
      matrix degradation mechanisms in aseptic prosthesis loosening (APL), rheumatoid
      arthritis (RA), and osteoarthritis (OA), we immunohistochemically examined the
      expressions of matrix metalloproteinase-1 and cathepsins B, D, and L in
      periprosthetic synovial-like interface tissues from 32 patients with failed
      prosthetic hips, from 29 RA-patients with hip synovial membranes, and from 35
      patients with primary OA. Numerical values, calculated for the positivity of each
      protease, were used to rank the staining patterns, and a multivariate analysis
      was carried out to examine the discriminant probabilities. As a result of
      stepwise linear discriminant analyses, the three groups were successfully
      discriminated with probabilities of 100%, 62.1%, and 77.1%, respectively.
      Cathepsin L was significantly related to the discrimination of APL from RA and
      primary OA. Disease-specific protease activation pathways might exist, and
      cathepsin L can be a key enzyme for APL pathogenesis. LEVEL OF EVIDENCE:
      Prognostic study, level III (retrospective study).

PMID- 17540511
TI  - [Polycystic ovary syndrome (PCOS)].
AB  - Polycystic ovaries syndrome (PCOS) is one of the most common female hormonal
      disorders. Its multiple components--reproductive, metabolic, neoplasic and
      cardiovascular--have a major impact on the public health. Androgen excess and
      resistance to insulin, probably from genetic origin, are responsible for most of
      the clinical symptomatology. Resistance to insulin seems to be accompanied by a
      greater risk of glucose intolerance, type 2 diabetes, lipidic anomalies and can
      involve the development of cardiovascular diseases. In addition, sleep apnea
      syndrome is more progressively described in PCOS. Infertility, menses disorders
      and hirsutism often push these patients to consult their physician. A better
      understanding of the physiopathological mechanisms led to the emergence of new
      therapeutic options increasing the sensitivity to insulin. Besides the pregnancy
      wishes, cares aim to attenuate the marks of the hyper-androgenism (hormonal
      treatment and cosmetic) and to correct cardiovascular, respiratory and
      gynaecological risk factors. In case of infertility by anovulation, cares must be
      performed by trained experts to minimize the risk of ovarian hyper-stimulation
      syndrome and multiple pregnancies. A gradation from loose weight to clomiphene
      citrate ovulation induction, ovarian drilling, low dose gonadotropin, in vitro
      fertilisation, or in vitro maturation of oocytes should bring back good
      reproduction potential.

PMID- 17540512
TI  - [Surgical treatment for female stress urinary incontinence by transobturator tape
      (outside in). Study of 70 cases].
AB  - OBJECTIVES: To evaluate the feasibility, the efficacy and the innocuousness of
      suburethral transobturator support using multifilament polypropylene
      transobturator tape (TOT) inside out for stress urinary incontinence in women.
      MATERIALS AND METHODS: The study concerns 70 patients representing our team's
      first experience of this technique. The inclusion criterion was persistent SUI
      despite perineal rehabilitation. There were no exclusion criteria. Among the 70
      patients, 22 (31%) presented with associated genital prolapse. Mean parity was
      2.6 (extremes ranging from 0 to 6). Thirty-five patients were menopaused (50%),
      of whom 12 (34%) were under hormone replacement therapy. We retained five
      judgement criteria to evaluate this surgical act: duration of surgery and
      hospitalisation, per- and postoperative complications and functional results on
      SUI (via a telephone questionnaire). RESULTS: The rate of positive results
      (healing or improvement) was 84% with a mean follow-up of 14.5 months. The rate
      of peroperative complications was very low: 1.4% (only one case of bladder
      injury). The mean duration of surgery was 23 minutes. The mean duration of
      hospitalisation in the case of isolated TOT was 1.25 days. CONCLUSION: The
      transobturator approach is a feasible, safe and efficient short-term surgical
      technique. Results inferior to those observed in the literature are probably due
      to the learning curve in a university hospital unit. None of the preoperative
      data (age, parity, body mass index, history of SUI treatment or hysterectomy,
      hormonal status, associated prolapse, mean urethral closure pressure, clinical
      vesical hyperactivity syndrome) appears to influence results; however, the study
      strength is poor due to the small study population.

PMID- 17540513
TI  - Learned helplessness: effects of response requirement and interval between
      treatment and testing.
AB  - Three experiments investigated learned helplessness in rats manipulating response
      requirements, shock duration, and intervals between treatment and testing. In
      Experiment 1, rats previously exposed to uncontrollable or no shocks were tested
      under one of four different contingencies of negative reinforcement: FR 1 or FR 2
      escape contingency for running, and FR1 escape contingency for jumping (differing
      for the maximum shock duration of 10s or 30s). The results showed that the
      uncontrollable shocks produced a clear operant learning deficit (learned
      helplessness effect) only when the animals were tested under the jumping FR 1
      escape contingency with 10-s max shock duration. Experiment 2 isolated of the
      effects of uncontrollability from shock exposure per se and showed that the
      escape deficit observed using the FR 1 escape jumping response (10-s shock
      duration) was produced by the uncontrollability of shock. Experiment 3 showed
      that using the FR 1 jumping escape contingency in the test, the learned
      helplessness effect was observed one, 14 or 28 days after treatment. These
      results suggest that running may not be an appropriate test for learned
      helplessness, and that many diverging results found in the literature might be
      accounted for by the confounding effects of respondent and operant contingencies
      present when running is required of rats.

PMID- 17540514
TI  - A model of globin evolution.
AB  - Putative globins have been identified in 426 bacterial, 32 Archaeal and 67
      eukaryote genomes. Among these sequences are the hitherto unsuspected presence of
      single domain sensor globins within Bacteria, Fungi, and a Euryarchaeote.
      Bayesian phylogenetic trees suggest that their occurrence in the latter two
      groups could be the result of lateral gene transfer from Bacteria. Iterated
      psiblast searches based on groups of globin sequences indicate that bacterial
      flavohemoglobins are closer to metazoan globins than to the other two lineages,
      the 2-over-2 globins and the globin-coupled sensors. Since Bacteria is the only
      kingdom to have all the subgroups of the three globin lineages, we propose a
      working model of globin evolution based on the assumption that all three lineages
      originated and evolved only in Bacteria. Although the 2-over-2 globins and the
      globin-coupled sensors recognize flavohemoglobins, there is little recognition
      between them. Thus, in the first stage of globin evolution, we favor a
      flavohemoglobin-like single domain protein as the ancestral globin. The next
      stage comprised the splitting off to single domain 2-over-2 and sensor-like
      globins, followed by the covalent addition of C-terminal domains resulting in the
      chimeric flavohemoglobins and globin-coupled sensors. The last stage encompassed
      the lateral gene transfers of some members of the three globin lineages to
      specific groups of Archaea and Eukaryotes.

PMID- 17540515
TI  - Gene regulation in the marine diatom Thalassiosira pseudonana upon exposure to
      polycyclic aromatic hydrocarbons (PAHs).
AB  - Diatoms are eukaryotic algae, which can be found worldwide in oceans and
      freshwaters. These organisms are ecologically relevant due to their key role in
      the global carbon cycle, contributing to about 25% to the global primary
      production [Falciatore, A., Bowler, C., 2002. Revealing the molecular secrets of
      marine diatoms. Annu. Rev. Plant Biol. 53, 109-130]. We investigated the effects
      of three polycyclic aromatic hydrocarbons (PAHs, pyrene, fluoranthene, and
      benzo[a]pyrene), either as single compound or as mixture, at molecular level.
      Dose-response curves for growth inhibition were determined and four
      concentrations eliciting from "no effect" up to a severe growth inhibition were
      chosen for further investigation to detect alterations at gene expression level
      by Real-Time PCR. Among the eight selected genes, two were strongly influenced by
      the PAH treatment. lacsA, which is involved in the fatty acid metabolism, was
      found to be strongly up-regulated by all single PAHs, as well as by the mixture.
      sil3, involved in the formation of the silica shell, was repressed by a factor up
      to three even at low PAH concentrations not eliciting any growth inhibition. For
      other genes, involved e.g. in photosynthesis, a slight down-regulation was
      detected. Based on the effects at gene expression level it can be assumed that
      PAHs impair the fatty acid metabolism and silica shell formation.

PMID- 17540516
TI  - Plant hemoglobins: what we know six decades after their discovery.
AB  - This review describes contributions to the study of plant hemoglobins (Hbs) from
      a historical perspective with emphasis on non-symbiotic Hbs (nsHbs). Plant Hbs
      were first identified in soybean root nodules, are known as leghemoglobins (Lbs)
      and have been characterized in detail. It is widely accepted that a function of
      Lbs in nodules is to facilitate the diffusion of O(2) to bacteroids. For many
      years Hbs could not be identified in plants other than N(2)-fixing legumes,
      however in the 1980s a Hb was isolated from the nodules of the non-legume dicot
      plant Parasponia, a hb gene was cloned from the non-nodulating Trema, and Hbs
      were detected in nodules of actinorhizal plants. Gene expression analysis showed
      that Trema Hb transcripts exist in non-symbiotic roots. In the 1990s nsHb
      sequences were also identified in monocot and primitive (bryophyte) plants. In
      addition to Lbs and nsHbs, Hb sequences that are similar to microbial truncated
      (2/2) Hbs were also detected in plants. Plant nsHbs have been characterized in
      detail. These proteins have very high O(2)-affinities because of an extremely low
      O(2)-dissociation constant. Analysis of rice Hb1 showed that distal His
      coordinates heme Fe and stabilizes bound O(2); this means that O(2) is not
      released easily from oxygenated nsHbs. Non-symbiotic hb genes are expressed in
      specific plant tissues, and overexpress in organs of stressed plants. These
      observations suggest that nsHbs have functions additional to O(2)-transport, such
      as to modulate levels of ATP and NO.

PMID- 17540517
TI  - Campylobacter-induced interleukin-8 responses in human intestinal epithelial
      cells and primary intestinal chick cells.
AB  - Campylobacter (C.) jejuni and C. coli can cause gastrointestinal disorders in
      humans characterized by acute inflammation. Inflammatory signals are initiated
      during interaction between these pathogens and human intestinal cells, but
      nothing is known about the stimulation of avian intestinal cells by
      Campylobacter. Interleukin-8 (IL-8) as a proinflammatory chemokine plays an
      important role in mobilizing cellular defence mechanism. IL-8 mRNA expression in
      both human intestinal cells (INT 407) and primary intestinal chick cells (PIC)
      was determined by quantitative real-time RT-PCR. The secretion of IL-8 protein by
      INT407 was measured using ELISA. Although C. jejuni and C. coli are considered to
      be harmless commensals in the gut of birds, the avian Campylobacter isolates
      investigated were able to induce the proinflammatory IL-8 in PIC as well as in
      INT407. In an in vitro system, C. jejuni as well as C. coli were able to induce
      IL-8 mRNA in PIC. Relation between the virulence properties like toxin
      production, the ability to invade and to survive in Caco-2 cells and the level of
      IL-8 mRNA produced by INT 407 and PIC after infection with Campylobacter strains
      was also investigated.

PMID- 17540518
TI  - Relatedness of cytotoxins from geographically diverse isolates of Moraxella
      bovis.
AB  - To determine whether amino acid sequence variation exists in the Moraxella bovis
      (M. bovis) cytotoxin (MbxA) from geographically diverse M. bovis isolated in the
      United States, mbxA was amplified and sequenced. The MbxA deduced amino acid
      sequence from M. bovis originally isolated in California, Washington, North
      Carolina, and Georgia, as well as reference strains of M. bovis isolated at the
      National Animal Disease Laboratory, Ames, IA, USA, all encoded a nearly identical
      927 amino acid protein. MbxA from two of the four California isolates (SFS 9a and
      SFS 100a) differed from all other isolates at two sites at which the polar amino
      acids glutamine (position 666) and asparagine (position 823) were replaced by
      ionized amino acids glutamic acid and aspartic acid, respectively. Rabbit
      antiserum to the expressed carboxy terminus (amino acids 590-927) of MbxA from M.
      bovis (Tifton I) neutralized the hemolytic activity of SFS 9a and SFS 100a. The
      M. bovis cytotoxin appears to be conserved amongst geographically diverse
      isolates of M. bovis from the USA. Antiserum against the carboxy terminus of MbxA
      common to the majority of isolates neutralized the hemolytic activity of two
      strains with a divergent MbxA deduced amino acid sequence. Vaccines against IBK
      that incorporate MbxA as antigen may offer protection against geographically
      diverse strains of M. bovis.

PMID- 17540519
TI  - Analytical applications of Fourier transform-infrared (FT-IR) spectroscopy in
      microbiology and prion research.
AB  - A genuine biophysical method, Fourier transform-infrared (FT-IR) spectroscopy has
      become a versatile research tool in biochemistry and biomedicine. Topical
      applications in microbiology and prion research are impressive illustrations of
      the vigorous evolution of the technique. FT-IR spectroscopy has established
      itself as a powerful method for the rapid differentiation and identification of
      microorganisms, thereby contributing to both clinical medicine and the prevention
      of bioterrorism. It has also led to considerable progress in various other fields
      of basic research, not least in prion sciences. In this field, FT-IR spectroscopy
      has been increasingly applied as a tool for elucidating structural features of
      the pathological prion protein, and also to study the molecular changes induced
      by prions in neuronal tissue and blood. This article sets out to give a review of
      current examples of the analytical potential of FT-IR spectroscopy in
      microbiology and prion research.

PMID- 17540520
TI  - Comparison of the antibacterial activity of honey from different provenance
      against bacteria usually isolated from skin wounds.
AB  - The antibacterial activity of honey samples provided by apiarists and honey
      packers was tested against microorganisms usually isolated from skin wounds. The
      antibacterial activity was tested using the well-agar diffusion assay. The honey
      samples were tested without dilution, and at 75, 50, 30, and 10% (w/v) dilution.
      Most of the undiluted honey samples inhibited the growth of Staphylococcus aureus
      and Staphylococcus epidermidis. Some honey samples provided by apiarists also
      inhibited the growth of S. aureus even at 50% dilution. Undiluted honey samples
      also inhibited the growth of Staphylococcus uberis, Pseudomonas aeruginosa,
      Escherichia coli, and Klebsiella pneumoniae, although to a lesser extent. No
      inhibition of Micrococcus luteus and Enterococcus faecalis growth was detected.
      The diameters of the inhibition zones generated by honey samples provided by
      apiarists were larger than those generated by honey samples provided by honey
      packers. This observation may be explained by considering the provenance of the
      honey samples.

PMID- 17540521
TI  - Transcription factor Nrf2 activation by deltamethrin in PC12 cells: Involvement
      of ROS.
AB  - Activation of transcription factor NF-E2-related factor 2 (Nrf2) is a key
      initiation step in the cellular protection against a broad range of chemical
      oxidative stresses. To gain insights into dopaminergic cell responses to
      pesticides, the present study was conducted to examine the effects of
      deltamethrin (DM), a prototype of widely used pyrithroid pesticides, on the
      activation and expression of Nrf2 in PC12 rat adrenal pheochromocytoma cells as a
      dopaminergic cell model. We found, for the first time, that DM enhanced cellular
      expression of Nrf2 at the transcriptional and protein levels and activated
      expression of Nrf2-regulated genes in these cells. In addition, DM exposure
      caused nuclear accumulation of Nrf2 in association with downstream activation of
      Nrf2-mediated oxidative response genes, such as heme oxygenase-l (HO-1) and gamma
      glutamylcysteine synthetase catalytic heavy subunit (GCSh). Furthermore, when
      cells were pretreated with N-acetyl cysteine (NAC), a scavenger of reactive
      oxygen species (ROS), DM-induced Nrf2 signaling was suppressed. These results
      indicate that ROS is the mediator of nuclear Nrf2 accumulation. Taken together,
      these data clearly show that DM increases Nrf2 expression and activity and that
      ROS is one of the mediators of this process.

PMID- 17540522
TI  - Neutralization of snake venom phospholipase A2 toxins by aqueous extract of
      Casearia sylvestris (Flacourtiaceae) in mouse neuromuscular preparation.
AB  - Aqueous extract of Casearia sylvestris (Flacourtiaceae) has been shown to inhibit
      enzymatic and biological properties of some Bothrops and Crotalus venoms and
      their purified phospholipase A(2) (PLA(2)) toxins. In this work we evaluated the
      influence of C. sylvestris aqueous extract upon neuromuscular blocking and muscle
      damaging activities of some PLA(2)s (crotoxin from C. durissus terrificus,
      bothropstoxin-I from B. jararacussu, piratoxin-I from B. pirajai and myotoxin-II
      from B. moojeni) in mouse phrenic-diaphragm preparations. Crotoxin (0.5 microM)
      and all other PLA(2) toxins (1.0 microM) induced irreversible and time-dependent
      blockade of twitches. Except for crotoxin, all PLA(2) toxins induced significant
      muscle damage indices, assessed by microscopic analysis. Preincubation of
      bothropstoxin-I, piratoxin-I or myotoxin-II with C. sylvestris extract (1:5
      (w/w), 30 min, 37 degrees C) significantly prevented the neuromuscular blockade
      of preparations exposed to the mixtures for 90 min; the extent of protection
      ranged from 93% to 97%. The vegetal extract also neutralized the muscle damage
      (protection of 80-95%). Higher concentration of the C. sylvestris extract (1:10,
      w/w) was necessary to neutralize by 90% the neuromuscular blockade induced by
      crotoxin. These findings expanded the spectrum of C. sylvestris antivenom
      activities, evidencing that it may be a good source of potentially useful PLA(2)
      inhibitors.

PMID- 17540523
TI  - Flavonoids with anti-inflammatory and antinociceptive activity from Cistus
      laurifolius L. leaves through bioassay-guided procedures.
AB  - Extracts obtained from the leaves and branches of various Cistus species have
      been used worldwide as folk remedy for the treatment of various inflammatory
      ailments including rheumatism and renal inflammations. Effects of the extracts
      and fractions from the leaves with non-woody branches of Cistus laurifolius L.
      (Cistaceae) were studied using two in vivo models of inflammation in mice. Model
      one was based on observed potent inhibitory activity against carrageenan-induced
      hind paw oedema and the second model used was acetic acid-induced, increased
      vascular permeability model. Through bioassay-guided fractionation and isolation
      procedures three flavonoids; 3-O-methylquercetin (1), 3,7-O-dimethylquercetin (2)
      and 3,7-O-dimethylkaempferol (3) were isolated as the main active ingredients
      from the ethanol extract. Later on, these flavonoids were shown to possess potent
      antinociceptive activity, which was assessed through inhibition of p-benzoquinone
      induced writhing reflex. Results of the present study have clearly supported the
      utilization of Cistus laurifolius in Turkish traditional medicine. Subsequently,
      three flavonoids were shown to have strong antinociceptive and anti-inflammatory
      activities, per os without inducing any apparent acute toxicity as well as
      gastric damage.

PMID- 17540524
TI  - Dental age in Central Poland.
AB  - Precise evaluation of the developmental stage of a child is an integral part of
      both diagnosis and treatment of pediatric patients; it is also essential in
      forensic medicine and dentistry. Among radiological methods for dental age
      estimation in children the Demirjian's method is widely used, however original
      standards elaborated for the French-Canadian population are mostly not suitable
      for other populations. The aim of the study was to compare the dental age of
      children from the region of Mazovia (Central Poland) with the developmental
      standards presented by Demirjian, to analyse sexual dimorphism of dental age in
      the studied group and to estimate validity of the Demirjian's standards for the
      studied Polish population. The material consisted of clinical files and panoramic
      X-ray images of 994 children aged from 6 to 16 in good general health, without
      development impairments. Chronological ages of the patients were established.
      Next dental ages were estimated by means of the Demirjian method based on
      developmental maturity of seven left mandibular permanent teeth. It was found
      that the standards were significantly different from the chronological ages in
      the studied population, which means that dental development was considerably
      accelerated. The most significant acceleration was observed in girls aged 11 and
      12, as well as in 13-year-old boys; in both groups a considerable acceleration of
      the dental age was seen in 6-year-olds. No statistically significant differences
      between dental ages of girls and boys were observed in particular age groups.
      There were devised gender-specific equations allowing for adaptation of original
      Demirjian's scores for estimation of dental age in the population of Mazovia
      (Central Poland). In conclusion, the developmental standards used by Demirjian
      are not suitable in the case of the population of children of Central Poland.
      Therefore, it is necessary to establish new tables for this population.

PMID- 17540526
TI  - Improvement of lung abnormality detection in computed radiography using multi
      objective frequency processing: Evaluation by receiver operating characteristics
      (ROC) analysis.
AB  - Computed radiography (CR) has been shown to have relatively low sensitivity for
      detection of pulmonary nodules. This poor sensitivity precludes its use as a
      screening modality despite the low cost, low dose and wide distribution of
      devices. The purpose of this study was to apply multi-objective frequency
      processing (MFP) to CR images and to evaluate its usefulness for diagnosing
      subtle lung abnormalities. Fifty CR images with simulated subtle lung
      abnormalities were obtained from 50 volunteers. Each image was processed with
      MFP. We cut chest images. The chest image was divided into two rights and left. A
      total of 200 half-chest images (100 MFP-processed images and 100 MFP-unprocessed
      images) were prepared. Five radiologists participated in this study. ROC analyses
      demonstrated that the detection rate of simulated subtle lung abnormalities on
      the CR images was significantly better with MFP (Az=0.8508) than without MFP
      (Az=0.7925). The CR images processed with MFP could be useful for diagnosing
      subtle lung abnormalities. In conclusion, MFP appears to be useful for increasing
      the sensitivity and specificity in the detection of pulmonary nodules, ground
      glass opacity (GGO) and reticular shadow.

PMID- 17540525
TI  - Effects of life-long caloric restriction and voluntary exercise on age-related
      changes in levels of catecholamine biosynthetic enzymes and angiotensin II
      receptors in the rat adrenal medulla and hypothalamus.
AB  - We examined if life-long mild caloric restriction (CR) alone or with voluntary
      exercise prevents the age-related changes in catecholamine biosynthetic enzyme
      levels in the adrenal medulla and hypothalamus. Ten-week-old Fisher-344 rats were
      assigned to: sedentary; sedentary+8% CR; or 8% CR+wheel running. Rats were
      euthanized at 6 or 24 months of age. Tyrosine hydroxylase (TH) mRNA expression
      was 4.4-fold higher in the adrenal medullae and 60% lower in the hypothalamus of
      old sedentary rats compared to young (p<0.01). Life-long CR reduced the age
      related increase in adrenomedullary TH by 50% (p<0.05), and completely reversed
      the changes in hypothalamic TH. Voluntary exercise, however, had no additional
      effect over CR. Since angiotensin II is involved in the regulation of
      catecholamine biosynthesis, we examined the expressions of angiotensin II
      receptor subtypes in the adrenal medulla. AT(1) protein levels were 2.8-fold
      higher in the old animals compared to young (p<0.01), and while AT(1) levels were
      unaffected by CR alone, CR+wheel running decreased AT(1) levels by 50% (p<0.01).
      AT(2) levels did not change with age, however CR+wheel running increased its
      level by 42% (p<0.05). These data indicate that a small decrease in daily food
      intake can avert age-related changes in catecholamine biosynthetic enzyme levels
      in the adrenal medulla and hypothalamus, possibly through affecting angiotensin
      II signaling.

PMID- 17540527
TI  - Is HPLC assay for drug substance a useful quality control attribute?
AB  - HPLC is a generally accepted method for assay of drug substances. However, recent
      claims cast doubts on the utility of HPLC assay methods for characterizing
      quality [S. Gorog, J. Pharm. Biomed. Anal. 36 (2005) 931-937]. This study
      examines the utility of the traditional drug substance HPLC assay as a quality
      control parameter. HPLC assay data from more than 100 batches for each of eight
      drug substances were compared to results from a mass balance approach (100
      impurities%). Estimates of the variability of HPLC assays from our data and from
      the literature ranged from 0.6 to 1.1% R.S.D. This variability is an appreciable
      portion of a typical acceptance range (e.g., 98.0-102.0%) and frequently exceeds
      the variability of the manufacturing process. Therefore, the results of the HPLC
      assay are questionable at best to determine the acceptability of the drug
      substance batch. The high variability also can generate a significant percentage
      of false out-of-specification (OOS) results, even when the "true" purity is 99.0
      100.0%. Each false OOS leads to inefficiencies because of unwarranted
      investigations for a root cause and/or implementation of countermeasures for a
      problem that does not exist. Lastly, low precision makes it nearly impossible to
      detect significant changes in the process mean and/or degradation during a
      stability study. The use of a mass balance approach for assay retains essentially
      the same average results as the HPLC assay but gives standard deviations that are
      up to 10 times less. Monitoring the assay by mass balance allows for more precise
      process and stability monitoring and facilitates more rapid and accurate
      identification of process changes.

PMID- 17540528
TI  - Gas chromatographic-mass spectrometric analysis of d-limonene in human plasma.
AB  - d-Limonene shows carminative and cholagogue effects and is used in treatment of
      gallstone, cholecystitis and angiocholitis. A simple method was developed to
      determine the concentration of d-limonene in human plasma. d-Limonene and
      internal standard (naphthalane, C(10)H(18)) were extracted with n-hexane and then
      injected to GC-MS. Calibration curves were linear (r=0.9990, n=6) in the range of
      2-500 ng/ml for d-limonene in human plasma. Limit of detection and quantification
      were 0.5 and 2 ng/ml, respectively. This rapid and specific method was applied to
      the clinical pharmacokinetic investigation of d-limonene.

PMID- 17540529
TI  - Validation of an isocratic LC method for determination of quercetin and
      methylquercetin in topical nanoemulsions.
AB  - The aim of this study was to validate an isocratic LC method for the
      quantification of either quercetin (Q) or methylquercetin (MQ) incorporated in
      topical nanoemulsions. The analyses were performed at room temperature on a
      reversed-phase C(18) column using a mobile phase composed of methanol/water
      (70:30, v/v) and trifluoracetic acid 0.1% at 0.8 mL min(-1). The detection was
      carried out on a UV detector at 368 or 354 nm for Q and MQ, respectively. The
      linearity, in the range of 0.15-1.5 microg/mL, presented a determination
      coefficient (r(2)) higher than 0.99, calculated by the least square method for
      both flavonoids. No interferences from the excipients (egg-lecithin or
      octyldodecanol) were detected. The R.S.D. values for intra- and inter-day
      precision experiments were lower than 2% for both flavonoids. The recovery ranged
      from 98.9% to 103.46% for Q and from 98.9% to 102.92% for MQ.

PMID- 17540530
TI  - Beyond content analysis and non-verbal behaviour - what about atmosphere? A
      phenomenological approach.
AB  - OBJECTIVE: Basic research and careful observation of clinical practice have
      yielded a vast amount of empirical data on communication in health care. This
      research has been guided by the assumption that good communication will be better
      understood and easier to teach when its single constituents are identified. This
      paper points to the limitation of this approach. METHODS: Based upon the
      terminology of phenomenological thinking grounded in neo-phenomenology (Hermann
      Schmitz) contradictory findings from the literature on patient-centred
      communication in Internal Medicine and Oncology are used as a starting point to
      elucidate different paradigms in conducting research in clinical communication.
      RESULTS: The phenomenological approach of the German philosopher Hermann Schmitz
      (*1928) is briefly presented. It is based upon experiences that 'on the average
      everybody can vividly access or retrieve from his memory'. Empirical research
      does not provide unequivocal advice how to communicate with an individual
      patient. Likewise, researchers note unexpected reactions from real patients-they
      do not behave as the expert would assume. The inclusion of the phenomenon of a
      certain atmosphere is proposed referring to the impression of 'something in the
      air' that sometimes can be identified during communication or upon entering a
      room. Even though it can be sensed with high evidence, it cannot be deduced from
      particular observations. Instead, the atmosphere is part of a situation in which
      meaning is dissolved in chaotic manifoldness. Sensing an atmosphere is a function
      of the lived body (Leib) as opposed to phenomena that are mediated by the senses.
      CONCLUSION: Current research and teaching models cover only part of the
      phenomenology of professional communication. How research and education might
      profit from the addition of Schmitz' philosophical approach will be outlined in
      this article. PRACTICE IMPLICATIONS: Including perceptions of the lived body
      (Leib) should improve research in clinical communication and teaching courses.

PMID- 17540531
TI  - Online on-the-spot searching increases use of evidence during consultations in
      family practice.
AB  - OBJECTIVE: The project aimed to search for online evidence in a structured way in
      consultation with the patient, to investigate whether the evidence discovered
      changed decisions. METHODS: We developed the "Online on-the-spot" method (OOS) as
      a part of a quality improvement program. Within a general practice consultation
      three physicians and two trainees searched in a fixed pattern and sequence the
      national guidelines of general practitioners developed by the Dutch College of
      General Practitioners, Clinical Evidence, Trip-database and the British Medical
      Journal. All GPs who performed this quality improvement program were in favor of
      the project. RESULTS: During 3 months five GPs registered 365 searches out of
      2920 patient-doctor contacts. For each eight patient-doctor contacts there was
      one online search. Patients were actively involved in 53% of the searches
      (95%C.I.: 48-57%). On average, two databases were consulted. An answer to the
      question was found in 87% of cases and in almost half of cases it was relevant
      new information for the doctor. The GP changed his decision due to the problem in
      26% (95%C.I.: 21-29) of cases. At the end of the OOS project, the number of
      searches within 5 min were significantly higher than at the start: 51% (95% C.I.:
      44-59) to 33% (95% C.I.: 24-43), respectively. CONCLUSIONS: The OOS project is a
      timely answer to the doctors' educational needs in attending to the patient.
      PRACTICE IMPLICATIONS: OOS could connect the patient, the doctor and the
      evidence.

PMID- 17540532
TI  - Physical activity, walking exercise, and calf skeletal muscle characteristics in
      patients with peripheral arterial disease.
AB  - OBJECTIVE: This cross-sectional study was set in an academic medical center and
      conducted to identify associations of physical activity level and walking
      exercise frequency with calf skeletal muscle characteristics in individuals with
      lower extremity peripheral arterial disease (PAD). METHODS: Calf muscle
      characteristics in 439 men and women with PAD were measured with computed
      tomography at 66.67% of the distance between the distal and proximal tibia.
      Physical activity was measured continuously during 7 days with a vertical
      accelerometer. Patient report was used to determine the number of blocks walked
      during the past week and walking exercise frequency. Results were adjusted for
      age, sex, race, comorbidities, ankle-brachial index, body mass index, smoking,
      and other confounders. RESULTS: For both objective and subjective measures, more
      physically active PAD participants had higher calf muscle area and muscle
      density. Calf muscle area across tertiles of accelerometer-measured physical
      activity were first activity tertile, 5071 mm(2); second activity tertile: 5612
      mm(2); and third activity tertile, 5869 mm(2) (P < .001). Calf muscle density
      across tertiles of patient-reported blocks walked during the past week were first
      activity tertile, 31.4 mg/cm(3); second activity tertile, 33.0 mg/cm(3); and
      third activity tertile, 33.8 mg/cm(3) (P < .001). No significant associations
      were found between walking exercise frequency and calf muscle characteristics.
      CONCLUSION: Among participants with PAD, higher physical activity levels,
      measured by accelerometer and by patient-reported blocks walked per week, were
      associated with more favorable calf muscle characteristics. In contrast, more
      frequent patient-reported walking exercise was not associated with more or less
      favorable calf muscle characteristics. Results suggest that clinicians should
      encourage their patients to increase their walking activity during daily life.

PMID- 17540533
TI  - Optimizing compliance, efficiency, and safety during surveillance of small
      abdominal aortic aneurysms.
AB  - BACKGROUND: Outcome data documenting safety for observation of small abdominal
      aortic aneurysms (AAA 4.0 to 5.4 cm) are lacking outside of large clinical trials
      but requires near perfect patient compliance. This study describes a clinical
      pathway for AAA surveillance using a prospective database utilizing a nurse
      practitioner oversight to provide efficient use of clinic visits while
      maintaining a high level of patent participation. METHODS: Over a 7-year period
      (June 1999 through June 2006), 334 patients were enrolled in an AAA surveillance
      pathway at our academic veterans hospital. To minimize patient travel, clinic
      visitation was reserved for an initial examination with patient education and for
      discussion of intervention options in patients demonstrating AAA growth (>5.4 cm
      or expansion >1 cm/yr) during follow-up. Biannual ultrasound or CT imaging was
      scheduled and results discussed (after physician review) via telephone or "same
      day" direct patient contact. An electronic database was used to update patient
      information and plan follow-up. RESULTS: Compliance with the AAA surveillance
      pathway was achieved in 98.5% of patients, with only three patients (0.9%) lost
      to follow-up and two others (0.6%) choosing early repair at civilian
      institutions. At a mean interval of 29 months (+/-20 mo), surgical repair was
      performed in 225 (67%) patients by open (n = 143) or endovascular (n = 82)
      techniques for AAA growth to >5.4 cm (n = 219) or expansion by >1cm/yr (n = 6).
      One hundred six patients currently remain in surveillance. A single AAA rupture
      resulting in death occurred during surveillance (0.3%) and perioperative
      mortality (<60 days) was 0.9% in patients needing intervention for AAA growth.
      Cumulative aneurysm-related mortality was 0.9% for patients compliant with the
      AAA surveillance pathway. CONCLUSIONS: Use of a prospectively-maintained
      surveillance database managed by a non-physician provider with a reliance on
      telephone contact resulted in a high degree of patient compliance, reduced
      unnecessary patient travel, and provided practical clinic use. Limited additional
      resources were needed to implement our pathway and a similar approach may prove
      useful for large volume hospital, clinic, or practice systems.

PMID- 17540534
TI  - Exercise performance in patients with peripheral arterial disease who have
      different types of exertional leg pain.
AB  - OBJECTIVE: This study compared the exercise performance of patients with
      peripheral arterial disease (PAD) who have different types of exertional leg
      pain. METHODS: Patients with PAD were classified into one of four groups
      according to the San Diego Claudication Questionnaire: intermittent claudication
      (n = 406), atypical exertional leg pain causing patients to stop (n = 125),
      atypical exertional leg pain in which patients were able to continue walking (n =
      81), and leg pain on exertion and rest (n = 103). Patients were assessed on the
      primary outcome measures of ankle-brachial index (ABI), treadmill exercise
      measures, and ischemic window. RESULTS: All patients experienced leg pain
      consistent with intermittent claudication during a standardized treadmill test.
      The mean (+/- SD) initial claudication distance (ICD) was similar (P = .642)
      among patients with intermittent claudication (168 +/- 160 meters), atypical
      exertional leg pain causing patients to stop (157 +/- 130 meters), atypical
      exertional leg pain in which patients were able to continue walking (180 +/- 149
      meters), and leg pain on exertion and rest (151 +/- 136 meters). The absolute
      claudication distance (ACD) was similar (P = .648) in the four respective groups
      (382 +/- 232, 378 +/- 237, 400 +/- 245, and 369 +/- 236 meters). Similarly, the
      ischemic window, expressed as the area under the curve (AUC) after treadmill
      exercise, was similar (P = .863) in these groups (189 +/- 137, 208 +/- 183, 193
      +/- 143, and 199 +/- 119 AUC). CONCLUSION: PAD patients with different types of
      exertional leg pain, all limited by intermittent claudication during a
      standardized treadmill test, were remarkably similar in ICD, ACD, and ischemic
      window. Thus, the presence of ambulatory symptoms should be of primary clinical
      concern in evaluating PAD patients regardless of whether they are consistent with
      classic intermittent claudication.

PMID- 17540535
TI  - Criteria for defining significant central vein stenosis with duplex ultrasound.
AB  - OBJECTIVE: To determine criteria for a clinically significant vein stenosis with
      duplex ultrasound (DU) in patients with signs and symptoms of central venous
      outflow obstruction. METHODS: Patients referred with swelling with or without
      pain to the vascular laboratory to detect vein obstruction were evaluated. These
      were mostly patients who had liver transplant, dialysis access, and tumors. All
      patients had DU prior to any other imaging. Only patients who subsequently
      underwent phlebography with intention to treat the vein stenosis were included in
      the study. A phlebogram with two views, pressure measurements across the
      stenosis, and intravascular ultrasound in selected cases were performed in all
      patients with suspected stenosis on DU. Adjacent ipsilateral normal vein segments
      were utilized as controls. The invasive tests were performed within 2 weeks of
      the DU. Follow-up was performed with DU at discharge and within 6 months of the
      procedure. A pressure gradient of =3 mm Hg across the stenosis was used to define
      a >50% diameter reduction, which was also determined by phlebographic
      measurement. RESULTS: Thirty-seven patients, 20 males and 17 females, mean age 54
      years, range 27 to 79, were evaluated. Forty-one stenotic venous sites were
      detected with DU; inferior vena cava 14, superior vena cava 2, portal 2, iliac
      11, common femoral 3, brachiocephalic 3, subclavian 5, and axillary vein 1.
      Phlebography identified 37 of these stenoses and demonstrated two more not seen
      by DU. Pressure measurements confirmed 39 of those detected by DU. The best
      criterion by DU to detect a >50% stenosis was a poststenotic to pre-stenotic peak
      vein velocity ratio of 2.5. The presence of poststenotic turbulence and
      planimetric calculations of the diameter reduction increased the diagnostic
      confidence but not the accuracy. Using the pressure gradient of >/=3 mm Hg as a
      reference test, there were two false positive and two false negative exams with
      DU, while phlebography had two false negative exams. The overall agreement of DU
      alone was 90% of phlebography >95% and when combined 100%. Intravascular
      ultrasound identified correctly all 11 lesions in 11 patients. After angioplasty
      and stenting, there was a dramatic reduction in the edema in most patients
      particularly in those that had a caval stenosis. Restenosis was identified by DU
      in 5/29 (17%) patients at 6 months that were confirmed by phlebography and
      pressure measurements. Reintervention was performed in four and it was successful
      in three. CONCLUSIONS: DU is a sensitive method to identify a clinically
      significant vein stenosis. A peak vein velocity ratio of >2.5 across the stenosis
      is the best criterion to use for the presence of a pressure gradient of =3 mm Hg.
      DU can be used to select patients for intervention and also to monitor the
      success of the treatment during follow-up.

PMID- 17540536
TI  - [Non-HFE-related hereditary iron overload].
AB  - Hereditary iron overload is mainly due to mutations of the HFE gene, implicated
      in most cases of hereditary hemochromatosis. Non-HFE-related hereditary iron
      overload is rare. It includes hereditary hemochromatosis related to mutations of
      other genes, ferroportin disease (also known as hemochromatosis type 4), and
      entities associated with specific clinical manifestations. Four genes have been
      implicated in hereditary hemochromatosis: HFE and TFR2 (which codes for the
      second transferrin receptor), both involved in adult forms of hereditary
      hemochromatosis, and HAMP and HJV, which code for hepcidin and hemojuvelin,
      respectively, and are responsible for juvenile hemochromatosis. All types of
      hereditary hemochromatosis share common clinical and biological characteristics,
      including an autosomal recessive inheritance pattern, elevation of transferrin
      saturation as the initial manifestation, hepatic parenchymal iron overload, and
      sensitivity to therapeutic phlebotomy. They are due to hyperabsorption of dietary
      iron and are linked to a deficit of hepcidin, the principal iron regulator in the
      body. Ferroportin disease is a special dominantly inherited clinical form of iron
      overload due to mutations of the SLC40A1 gene. Its expression differs
      significantly from that of hereditary hemochromatosis, and its mechanism is
      related to impairment of iron release from reticuloendothelial cells. Other
      causes of non-HFE-related hereditary iron overload are usually associated with
      recognizable clinical manifestations, such as anemia or neurological disorders.

PMID- 17540537
TI  - Reciprocal inhibition of Cd and Ca uptake in isolated head kidney cells of
      rainbow trout (Oncorhynchus mykiss).
AB  - Some environmental pollutants, including cadmium (Cd) and zinc (Zn), can act as
      endocrine disruptors in fish, either in vivo or through a direct action on
      steroidogenic cells, as has been demonstrated in vitro. We have previously
      characterized Cd uptake in head kidney (homologue of mammalian adrenal) cells of
      rainbow trout (Oncorhynchus mykiss) and have provided evidence for a Cd/Ca
      interaction. Here, we pursued our investigation of metal competition for uptake.
      Our results show that inorganic speciation conditions favour Cd uptake with
      optimal level of accumulation for Cd2+ compared to chlorocomplexes (CdCl(n)(2
      n)). Calcium uptake was studied for the first time in the fish head kidney cells
      and Ca was found to be less efficiently accumulated compared to Cd. A specific
      saturable mechanism of transport was characterized for Ca uptake but voltage
      gated or La-sensitive cationic channels are unlikely to contribute appreciably. A
      concentration-dependent reciprocal inhibition was observed between Ca and Cd,
      whereas, Zn proved to inhibit Cd uptake exclusively. Additive inhibitory effect
      on Cd uptake was obtained with co-exposure to Ca and Zn. We conclude that Cd, but
      not Zn, may decrease Ca availability to the head kidney tissue. Also, Zn may
      partially protect against Cd toxicity but Zn would not protect against Cd-induced
      perturbation of Ca homeostasis.

PMID- 17540538
TI  - The influence of aetiology and blame on prejudice towards survivors of brain
      injury.
AB  - The purpose of the present work was to investigate if a hierarchy of aetiology
      exists which would influence attitudes towards survivors of brain injury. An
      independent groups design utilised four independent variables; aetiology
      (measured at five levels: 'Road Traffic Accident' (RTA), 'Alcohol', 'Drug Use',
      'Aneurysm' and 'Recreation'), blame (blame and no-blame), group (psychology
      students and members of the public) and gender to explore attitudes towards
      survivors of brain injury. The dependent variables were measured using the
      Prejudicial Evaluation Scale (PES) and Social Interaction Scale (SIS). Three
      hundred and twenty-five participants (173 students and 152 members of the public)
      were randomly allocated to 1 of 10 possible conditions. Among individuals who
      contributed to receiving their injury greater prejudice was displayed towards
      those in the 'Drugs' condition followed by 'Recreation', 'RTA', 'Alcohol' and
      'Aneurysm'. Findings suggest that a hierarchy of aetiology exists, which results
      in prejudicial attitudes, and is influenced by issues of blame.

PMID- 17540539
TI  - P2X7 receptor-mediated phosphatidic acid production delays ATP-induced pore
      opening and cytolysis of RAW 264.7 macrophages.
AB  - In macrophages, extracellular ATP (ATPe) stimulation of P2X7 receptors (P2X7R)
      results in cation channel opening, non-specific pore formation, secretion of
      cytokines, killing of intracellular bacteria and cytolysis. Signaling pathways
      controlling these diverse responses are currently under investigation. Among
      these pathways, phospholipase D (PLD) has been implicated in P2X7R-activated
      macrophages killing of intracellular pathogenic bacteria. Here we present
      evidence that early P2X7R-mediated PLD activation reduces pore opening and delays
      cytolysis of RAW 267.4 macrophages induced by ATPe. Use of inhibitors of PA
      metabolic enzymes suggests that PA, and not one of its metabolites, is the
      bioactive lipid. This is strengthened by the observation that addition of
      exogenous PA also reduces pore formation and cytolysis of RAW 264.7 macrophages.
      However, the beneficial effects of PA are only transient, due to its conversion
      into diacylglycerol through PA phosphatase-1 activity during prolonged P2X7R
      stimulation. Revealing that the PLD/PA pathway mediates survival of macrophages
      provides a potent strategy to inhibit P2X7R-mediated cytolysis by controlling PA
      metabolism. This will be important in the case of P2X7R-induced killing of
      intracellular bacteria which is lately associated with macrophage death, limiting
      the potency of ATPe to eliminate pathogenic bacteria.

PMID- 17540540
TI  - Omega-3 fatty acids and sudden cardiac death in schizophrenia: if not a friend,
      at least a great colleague.

PMID- 17540541
TI  - Reduction of synapsin III in the prefrontal cortex of individuals with
      schizophrenia.
AB  - We analyzed the expression of a presynaptic protein, synapsin III, in individuals
      with schizophrenia. Since levels of synapsin III were previously found to be
      significantly reduced in the hippocampus of individuals with schizophrenia, we
      examined another brain region believed to be a major locus of dysfunction in
      schizophrenia, the dorsolateral prefrontal cortex (DLPFC). Western blot analyses
      using tissue obtained from the Stanley Foundation Neuropathology Consortium
      revealed that synapsin III levels were significantly decreased in the DLPFC of
      individuals with schizophrenia compared to controls. These findings are
      consistent with growing evidence of presynaptic abnormalities and prefrontal
      cortical dysfunction in schizophrenia.

PMID- 17540542
TI  - Nationwide surveillance of Streptococcus pneumoniae in Greece: patterns of
      resistance and serotype epidemiology.
AB  - This nationwide study assessed the antimicrobial susceptibility and
      seroprevalence of Streptococcus pneumoniae in paediatric carriage isolates and in
      clinical isolates from adult pneumococcal disease in Greece during the years 2004
      2006. Among 780 isolates recovered from the nasopharynx of children <6 years old
      attending day-care centres, non-susceptibility rates to penicillin, cefuroxime,
      ceftriaxone, erythromycin, tetracycline and trimethoprim/sulfamethoxazole were
      34.7%, 25.1%, 1.0%, 33.5%, 26.4% and 44.2%, respectively. Among 89 adult clinical
      isolates, the respective rates were 48.3%, 46.1%, 5.6%, 48.3%, 32.6% and 40.4%.
      High-level resistance to penicillin, cefuroxime and ceftriaxone was recorded for
      14.4%, 23.3% and 0.1% of paediatric carriage isolates, whereas for clinical adult
      isolates the respective rates were 25.8%, 38.2% and 2.2%. No resistance to
      levofloxacin and moxifloxacin was recorded, although 3.5% of paediatric carriage
      isolates and 23.2% of adult clinical isolates had minimum inhibitory
      concentrations of ciprofloxacin >2mg/L. Serotypes 19F, 14, 23F and 6B were the
      most prevalent among carriage and clinical isolates. The 7-valent pneumococcal
      conjugate vaccine was estimated to provide coverage against 71.7% of paediatric
      carriage isolates and 51.3% of adult clinical isolates. Resistance rates among
      clinical isolates from adult sources were higher than those recorded among
      paediatric carriage S. pneumoniae isolates and displayed an increasingly
      resistant profile compared with previous reports from our country, warranting
      continuous vigilance.

PMID- 17540543
TI  - Improved blood compatibility of rapamycin-eluting stent by incorporating
      curcumin.
AB  - This paper dealt with improving the blood compatibility of the rapamycin-eluting
      stent by incorporating curcumin. The rapamycin- and rapamycin/curcumin-loaded
      PLGA (poly(d,l-lactic acid-co-glycolic acid)) coatings were fabricated onto the
      surface of the stainless steel stents using an ultrasonic atomization spray
      method. The structure of the coating films was characterized by Fourier transform
      infrared spectroscopy (FTIR). The optical microscopy and scanning electron
      microscopy (SEM) images of the drug-eluting stents indicated that the surface of
      all drug-eluting stents was very smooth and uniform, and there were not webbings
      and "bridges" between struts. There were not any cracks and delaminations on
      stent surface after expanded by the angioplasty balloon. The in vitro platelet
      adhesion and activation were investigated by static platelet adhesion test and
      GMP140 (P-selection), respectively. The clotting time was examined by activated
      partially prothromplastin time (APTT) test. The fibrinogen adsorption on the drug
      loaded PLGA films was evaluated by enzyme-linked immunosorbent assay (ELISA). All
      obtained data showed that incorporating curcumin in rapamycin-loaded PLGA coating
      can significantly decrease platelet adhesion and activation, prolong APTT
      clotting time as well as decrease the fibrinogen adsorption. All results
      indicated that incorporating curcumin in rapamycin-eluting coating obviously
      improve the blood compatibility of rapamycin-eluting stents. It was suggested
      that it may be possible to develop a drug-eluting stent which had the
      characteristics of not only good anti-proliferation but also improved
      anticoagulation.

PMID- 17540544
TI  - A simulation study with statistical evaluation for the determination of non
      isothermal kinetics conditions in drugs stability.
AB  - Non-isothermal degradations were applied to carry out simulation studies to
      analyse the influence of some factors on the accuracy and precision of stability
      parameters of drugs, to establish the best work conditions in experimental
      studies of stability using non-isothermal methodology. These factors were: random
      error added, sampling frequency, heating model, extent of drug degradation,
      amplitude of temperature range and mean temperature. Simulation studies were
      realized for a first-order degradation process. A weighted non-linear regression
      was used to determine the stability parameters which were statistically
      evaluated. An ANOVA analysis and post hoc comparisons tests were made to
      determine the statistical significance of the influence of each factor studied on
      the central value and on the precision of stability parameters of drugs.
      Univariant general linear model allowed to establish quantitatively the effect of
      the variability of the factors studied on the variability on the precision of the
      kinetic parameters. It was found that the influence of the studied factors was
      not statistically significant (p>0.05) on the activation energy (E(a)) and shelf
      life (t(90)) values. Nevertheless, four of the six analysed factors influenced
      with statistical significance on the precision of the shelf-life according the
      following decreasing order of importance: random error added, extent of drug
      degradation, amplitude of temperature range and heating model.

PMID- 17540545
TI  - Comparison between immobilized artificial membrane (IAM) HPLC data and
      lipophilicity in n-octanol for quinolone antibacterial agents.
AB  - The membrane phospholipid affinity of ten quinolone antibacterial agents,
      including both acidic and zwitterionic compounds, was measured by HPLC on two
      different immobilized artificial membrane (IAM) stationary phases, namely
      IAM.PC.MG and IAM.PC.DD2; it is expressed as the logarithm of the retention
      factor measured with (or extrapolated to) 100% aqueous eluent at pH 7.0,
      logk(w)(IAM). Quinolones are a class of highly potent, orally active, broad
      spectrum antibacterial agents. For these compounds, lipophilicity values in n
      octanol found in the literature, either calculated or measured, are not
      consistent with each other and are too low to be compatible with their
      pharmacokinetic properties. The logk(w)(IAM) values obtained in this study showed
      no relation with any of the lipophilicity values in the literature (clogP(a),
      clogP(b), MLP, logD(7.4)). In contrast, they were collinear with a new
      lipophilicity scale we had previously obtained by an original ion-pair reversed
      phase HPLC method set up to estimate the lipophilicity of the neutral forms,
      logP(N). Moreover, when comparing the retention of quinolones on IAM to the
      retention of structurally unrelated neutral compounds, we observed that they
      interact with phospholipids with the same affinity as neutral isolipophilic
      compounds. The use of an eluent at pH 5.5, instead of pH 7.0, increased the
      retention on IAM not only for acidic, but also for zwitterionic congeners,
      indicating that phospholipid affinity is enhanced in the experimental conditions
      that depress the ionization of the acidic function, even when the ionization of
      the amino function increases simultaneously. To gain an insight into the
      mechanism of quinolones/serum-protein interactions, we investigated about
      possible relationships between quinolones affinity data for serum proteins and
      IAM data. Quinolone affinity for both HSA and AGP was already demonstrated poorly
      related to n-octanol lipophilicity values, probably due to the occurrence of
      electrostatic interactions. Only poor relationships were found between IAM and
      HSA affinity data, whereas quite good relationships were found with AGP affinity
      data. However, IAM.PC.DD2 data correlated better than those on IAM.PC.MG with
      quinolone affinity for both serum-proteins, mainly due to the fact that IAM.PC.MG
      phase is scarcely discriminative for the compounds with the highest retention
      values. The results suggest that IAM retention can produce a lipophilicity scale
      that, unlike solvent/water partition coefficients, is consistent with the
      pharmacokinetic behaviour of zwitterionic quinolones.

PMID- 17540546
TI  - A sugar cane native dextran as an innovative functional excipient for the
      development of pharmaceutical tablets.
AB  - We reported the physical chemical characterization of a new series of native
      dextran (B110-1-2). The chemical structure of the polymer was characterized by
      IR, (1)H and (13)C NMR spectroscopy and compared with that of a commercial native
      dextran B512-F obtained from Sigma Company. Molecular weights of the product and
      different commercial dextran fractions of Leuconostoc mesenteroides from 43000 to
      170000 average molecular weight (M(w)) were established by the analysis of
      intrinsic viscosity in aqueous solutions and compared with those obtained by gel
      permeation chromatography (GPC). The critical overlap concentration around 9g/L
      was obtained. No interactions of powder mixtures with different commercial
      excipients (lactose, cetyl alcohol, HPMC) and drugs (propranolol hydrochloride,
      acetyl salicyclic acid, isosorbide dinitrate, lobenzarit disodium, and
      nifedipine) were demonstrated by differential scanning calorimetry (DSC)
      analysis. Tablets obtained by direct compression showed good physical-mechanical
      and technological properties. Dextran B110-1-2 has similar physical chemical
      properties as commercial Sigma B512-F. Water uptake, erosion and dissolution
      profile studies for dextran tablets established that glucose polymer with
      molecular weight M(w) > or = 2x10(6) is suitable for the development of
      controlled release solid dosage forms (soluble drugs). Fraction of dextran (M(w)
      40000-170000) could be more useful for immediate release tablets.

PMID- 17540547
TI  - Thermochemical analysis of the dissolution process of Griseofulvin.
AB  - Very often poor water solubility limits the therapeutic use of drug molecules. In
      order to develop strategies to overcome this handicap a basic understanding of
      this phenomenon is needed. In this paper Griseofulvin is used as a model
      substance. According to the Hess theorem the direct dissolution of Griseofulvin
      is replaced by a series of alternative processes which in their combination have
      the same starting point as well as the same endpoint as the direct dissolution.
      The energies associated with these alternative processes however can be
      determined more exactly than the dissolution energy. In cases where the
      measurement of an energy is impossible, e.g. the transfer energy of single
      molecules from the vapor phase into water, this energy is calculated by quantum
      chemical methods. In addition these alternative processes allow for a better
      understanding of the elementary steps involved in the dissolution process. The
      energies determined for the various alternative processes are compared with the
      dissolution energies as calculated by means of AMSOL. An excellent agreement can
      be observed.

PMID- 17540548
TI  - Oral low molecular weight heparin delivery by microparticles from complex
      coacervation.
AB  - As low molecular weight heparins exhibit limited oral absorption they usually
      have to be administered parenterally. Their strong negative charge appears to be
      one of the biggest hurdles to overcome in order to increase oral absorption.
      Complex coacervation has been proposed as a microencapsulation technique for
      increased oral drug absorption on the basis of charge compensation. Optimized
      tinzaparin/acacia gum mixture were coacervated with either gelatin A or B leading
      to microparticles with monodispersed size distribution, good fluidity and high
      encapsulation rates (>90%), while mean particle size varied between 5 and 20
      microm, respectively, depending on the gelatin type. Tinzaparin was homogeneously
      distributed throughout the particle matrix and anti-Xa activity was maintained
      during preparation and storage. Drug release occurred in dependency of the pH
      triggering the dissociation between tinzaparin/acacia and gelatin. Cell binding
      experiments on Caco-2 led to slightly increased adhesion of gelatin A
      microparticles compared to gelatin B (A: 3.5+/-0.3%; B: 2.5+/-0.3%; solution:
      1.9+/-0.1%), while drug transport did not differ from free tinzaparin solution.
      In-vivo results demonstrated an oral bioavailability of about 4.2+/-2.9% with
      gelatin B particles while gelatin A led to no absorption of tinzaparin. In
      conclusion, tinzaparin microparticles exhibited excellent particle properties in
      vitro and demonstrate potential for a formulation increasing the oral
      bioavailability of low molecular weight heparins.

PMID- 17540549
TI  - Biphasic release of indomethacin from HPMC/pectin/calcium matrix tablet: I.
      Characterization and mechanistic study.
AB  - Calcium-induced crosslinking of pectin acts as the dominating factor controlling
      drug release from pectin-based matrices. The same interaction was employed to
      modify indomethacin release from HPMC/pectin/calcium matrix in this study. The
      aim was to characterize the release profiles, and to study the formulation
      variables and the underlying mechanisms. The matrix tablet was made up of pectin
      HM 70, calcium chloride and HPMC K4M, and prepared by the wet granulation method.
      In vitro release was performed in water and characterized by the power law.
      Matrix erosion was evaluated by studying the weight loss and pectin release.
      Biphasic release of indomethacin from the HPMC/pectin/calcium matrix tablet was
      observed, and extraordinary power law exponent n values of over 1.0 were
      observed. Increase in calcium amount led to more significant retardation on drug
      release. The two power law parameters, n and K, correlated to the amount of
      calcium in the matrix. A lag time of over 4 h can be achieved at
      HPMC/pectin/calcium chloride amount of 100 mg/100 mg/100 mg. Both matrix weight
      loss and pectin release were linearly correlated to indomethacin release,
      indicating erosion-controlled drug release mechanisms. The hybrid matrix showed
      retarded erosion and hydration rate, which served as the basis for retarded
      indomethacin release. It is concluded that the pectin/calcium interaction can be
      employed to modify drug release from HPMC/pectin/calcium matrix tablet with
      biphasic release patterns for potential timed or site-specific drug delivery.

PMID- 17540550
TI  - Effect of excipients on the encapsulation efficiency and release of human growth
      hormone from dextran microspheres.
AB  - The possibility was investigated to modulate the encapsulation efficiency and
      release of human growth hormone (hGH) from hydroxyl ethyl methacrylated dextran
      (dex-HEMA) hydrogel microspheres by using excipients. Microspheres were prepared
      by polymerization of dex-HEMA in an aqueous two-phase system of this polymer and
      PEG with or without excipients (Tween 80, pluronic F68, sucrose, NaCl, urea or
      methionine). High hGH encapsulation efficiencies (50-70%) were obtained for
      microspheres prepared without excipients and with Tween 80, NaCl or methionine.
      Substantially lower encapsulation efficiencies (27% and 19%, respectively) were
      obtained for microspheres prepared in the presence of sucrose and urea, which was
      attributed to the more favoured partitioning of hGH over the PEG-phase due to
      higher hydrophobicity of the (partly) denatured hGH. Likely, differences in
      precipitate size of the encapsulated hGH resulted in different release profiles
      between microspheres prepared without excipients (biphasic release: 2 days delay
      time followed by 6 days release) and the release profile for microspheres
      prepared with Tween 80, pluronic F68, sucrose, NaCl and urea (release over a
      period of 6-8 days (without a delay time)). Microspheres prepared with methionine
      showed a concentration-dependent delay time varying from 0 to 2 days followed by
      almost zero-order release over 6 days, attributed to the effect of methionine on
      the polymerization of dex-HEMA. Especially, Tween 80 and methionine are
      attractive excipients since hGH was encapsulated in high yield (60-70%) and the
      protein was released from the microspheres mainly in its monomeric form without a
      delay time and with an almost zero-order release over 6-8 days.

PMID- 17540551
TI  - Enhancement of the dissolution of indomethacin in interactive mixtures using
      added fine lactose.
AB  - The objective of the study was to investigate the effect of fine lactose on the
      in vitro dissolution of indomethacin in interactive mixtures containing spray
      dried lactose and lactose monohydrate (106-250 microm). Dissolution of the
      indomethacin was measured using an automated dissolution apparatus following the
      USP paddle method at 100 rpm. The particle size distributions of indomethacin
      mixtures were measured using a Mastersizer S under non-sink conditions. Data
      fitted bi-exponential or tri-exponential dissolution models, representing
      dissolution from dispersed and agglomerated particle distributions. The addition
      of fine lactose (VMD 3.8+/-0.4 microm) to 20% indomethacin-coarse lactose
      mixtures resulted in significantly increased rates of dissolution caused by
      increases in the estimated dissolution rate constants for dispersed particles
      (Kd) and by de-agglomeration. Agglomerates in the mixture showed little tendency
      to comminute under shear pressure. De-agglomeration in the dissolution medium was
      attributed to increased porosity of agglomerates, caused by dissolution of water
      soluble fine lactose in the agglomerate structure. The median particle size (D50)
      of the dispersed particle distribution decreased with increasing concentrations
      of added fine lactose, indicating increasing extents of de-agglomeration, and a
      good correlation between Kd and (D50)2 resulted for the coarse lactose-based
      mixtures (R2>0.984).

PMID- 17540552
TI  - Liposomes for drug delivery to the lungs by nebulization.
AB  - Preparation of drug-loaded freeze-dried (FD) liposomes, designed for delivery to
      lungs after rehydration/nebulization was investigated. Rifampicin (RIF)
      incorporating multilamelar (MLV) and dried rehydrated vesicles (DRV); composed of
      phosphatidylcholine (PC), dipalmitoyloglycero-PC (DPPC) or distearoyloglycero-PC
      (DSPC), containing or not Cholesterol (Chol), were prepared. Vesicles were
      characterized for encapsulation efficiency (EE%), size distribution, zeta
      potential, stability during freeze drying (FD) and nebulization (nebulization
      efficiency (NE%) and retention of RIF after nebulization (NER%)). Mucoadhesion
      and toxicity in A549 cells was measured. RIF EE% was not affected by liposome
      type but lipid composition was important; Synthetic lipid vesicles (DPPC and
      DSPC) had higher EE% compared to PC. As Chol increased EE% decreased. Freeze
      drying (FD) had no effect on EE%, however trehalose decreased EE% possibly due to
      RIF displacement. NER% was highly affected by lipid composition. Results of NE%
      and NER% for RIF-loaded liposomes show that DSPC/Chol (2:1) is the best
      composition for RIF delivery in vesicular form to lungs, by nebulization.
      Mucoadhesion and A549 cell toxicity studies were in line with this conclusion,
      however if mucoadhesion is required, improvement may be needed.

PMID- 17540553
TI  - Why do patients decline to take part in a research project involving pulmonary
      rehabilitation?
AB  - BACKGROUND: It is important that those taking part in research trials are as
      representative as possible of those with the disease being studied. In a study of
      those with chronic obstructive pulmonary disease involving pulmonary
      rehabilitation, 120 of 297 suitable patients responded that they did not wish to
      take part in the trial. We were keen to know why these patients declined to take
      part in the study. METHODS: A total of 120 patients who had responded that they
      did not wish to take part in the main trial were approached to ask if they would
      be willing to undertake a semi-structured face-to-face interview in their own
      home or by telephone. Those who were willing (n=39) underwent tape-recorded
      interviews and data analysis was performed using the framework method. RESULTS:
      This was a qualitative study which revealed that several themes influenced
      patients' willingness or otherwise to take part in a research project involving
      pulmonary rehabilitation. Travelling to the hospital and location of the
      rehabilitation, along with competing commitments, and a variable perception of
      the benefits to the patient were clearly major factors and some had previous
      negative experiences of either the hospital, healthcare or research. While there
      was an element of negativity or impaired understanding regarding the research
      itself, the other factors appeared to be of greater importance. CONCLUSION:
      Recruitment to pulmonary rehabilitation courses or recruitment to research
      involving pulmonary rehabilitation may be more successful if the location of the
      rehabilitation can be made as near to the patient's home as possible, and if the
      patient is given as much information as possible about what is involved.

PMID- 17540554
TI  - Binding site characteristics of 17beta-estradiol imprinted polymers.
AB  - The variety of applications utilizing molecularly imprinted polymers (MIPs)
      requires synthetic strategies yielding different MIP formats including films,
      irregular particles, or spheres, along with precise knowledge on the specific
      material characteristics, such as binding capacity and binding efficiency of
      these materials. In response to this demand, MIPs are prepared in different
      formats by variation of the polymerization methodology. It is commonly agreed
      that micro- and sub-microspheres are particularly advantageous MIP formats, due
      to their monodispersity and facile synthesis procedures in contrast to
      conventional imprinted polymers prepared by bulk polymerization. However, the
      differences in actual rebinding characteristics of different MIP formats based on
      molecular interactions under a variety of binding/rebinding conditions have not
      been studied in detail to date. Consequently, the present work details an
      analytical strategy generically applicable to MIP systems for rebinding studies
      including equilibrium binding, non-equilibrium binding, and release experiments
      enabling more profound understanding on the molecular interactions between the
      imprinted materials and the template molecules. In this study, three MIP formats
      were considered for the same template molecule, 17beta-estradiol: irregularly
      shaped particulate polymers prepared by bulk polymerization and grinding,
      microspheres, and sub-microspheres. The latter two formats were synthesized via
      precipitation polymerization using different processing strategies. The
      morphologies and porosities of the resulting imprinted materials were
      characterized by scanning electron microscopy (SEM) and Brunauer-Emmett-Teller
      (BET) analysis, respectively. The obtained results indicate that microspheres
      prepared by precipitation polymerization provide superior rebinding properties
      during equilibrium binding in contrast to bulk polymers and sub-microspheres, and
      that the rebinding properties are different during equilibrium binding versus non
      equilibrium binding. The median binding affinity constant determined during non
      equilibrium rebinding is higher than the values obtained from equilibrium
      rebinding. Furthermore, the binding site distribution appears more homogeneous
      thief derived from non-equilibrium rebinding, as reflected in a heterogeneity
      index of m=0.725. Moreover, it is hypothesized that the specific interactions
      between template and monomers are related to the porosity of the imprinted
      polymers, which implies that the amount of binding sites and the pore sized
      distribution of the imprinted materials are a critical factor in achieving the
      desired MIP performance in various analytical applications. The BET results
      indicate that particles prepared with lower cross-linker-to-template ratio have a
      reduced surface area. Furthermore, it can be expected that there are less
      specific binding sites available at particles with reduced surface area and pore
      volume given similar distribution of the binding sites, as confirmed by the
      equilibrium binding isotherm studies. The pore size distribution results reveal
      that control of the pore size in the range of 100-180 A is essential to obtain
      the desired retention properties and Gaussian peak shape during HPLC analysis of
      small molecules.

PMID- 17540555
TI  - Does solar exposure, as indicated by the non-melanoma skin cancers, protect from
      solid cancers: vitamin D as a possible explanation.
AB  - BACKGROUND: Skin cancers are known to be associated with sun exposure, whereas
      sunlight through the production of vitamin D may protect against some cancers.
      The aim of this study was to assess whether patients with skin cancer have an
      altered risk of developing other cancers. METHODS: The study cohort consisted of
      416,134 cases of skin cancer and 3,776,501 cases of non-skin cancer as a first
      cancer extracted from 13 cancer registries. 10,886 melanoma and 35,620 non
      melanoma skin cancer cases had second cancers. The observed numbers (O) of 46
      types of second primary cancer after skin melanoma, basal cell carcinoma or non
      basal cell carcinoma, and of skin cancers following non-skin cancers were
      compared to the expected numbers (E) derived from the age, sex and calendar
      period specific cancer incidence rates in each of the cancer registries (O/E=SIR,
      standardised incidence ratios). Rates from cancer registries classified to sunny
      countries (Australia, Singapore and Spain) and less sunny countries (Canada,
      Denmark, Finland, Iceland, Norway, Scotland, Slovenia and Sweden) were compared
      to each other. RESULTS: SIR of all second solid primary cancers (except skin and
      lip) after skin melanoma were significantly lower for the sunny countries
      (SIR(S)=1.03; 95% CI 0.99-1.08) than in the less sunny countries (SIR(L)=1.14;
      95%CI 1.11-1.17). The difference was more obvious after non-melanoma skin
      cancers: after basal cell carcinoma SIR(S)/SIR(L)=0.65 (95%CI=0.58-0.72); after
      non-basal cell carcinoma SIR(S)/SIR(L)=0.58 (95%CI=0.50-0.67). In sunny
      countries, the risk of second primary cancer after non-melanoma skin cancers was
      lower for most of the cancers except for lip, mouth and non-Hodgkin lymphoma.
      CONCLUSIONS: Vitamin D production in the skin seems to decrease the risk of
      several solid cancers (especially stomach, colorectal, liver and gallbladder,
      pancreas, lung, female breast, prostate, bladder and kidney cancers). The
      apparently protective effect of sun exposure against second primary cancer is
      more pronounced after non-melanoma skin cancers than melanoma, which is
      consistent with earlier reports that non-melanoma skin cancers reflect cumulative
      sun exposure, whereas melanoma is more related to sunburn.

PMID- 17540556
TI  - Heavy metals (Cd, Pb, Zn, Ni, Cu and Cr(III)) removal from water in Malaysia:
      post treatment by high quality limestone.
AB  - This paper presents the results of research on heavy metals removal from water by
      filtration using low cost coarse media which could be used as an alternative
      approach to remove heavy metals from water or selected wastewater. A series of
      batch studies were conducted using different particle media (particle size 2.36
      4.75 mm) shaken with different heavy metal solutions at various pH values to see
      the removal behaviour for each metal. Each solution of cadmium (Cd), lead (Pb),
      zinc (Zn), nickel (Ni), copper (Cu) and chromium (Cr(III)) with a concentration
      of 2 mg/L was shaken with the media. At a final pH of 8.5, limestone has
      significantly removed more than 90% of most metals followed by 80% and 65%
      removals using crushed bricks and gravel, respectively. The removal by aeration
      and settlement methods without solid media was less than 30%. Results indicated
      that the removal of heavy metals was influenced by the media and not directly by
      the pH. Investigations on the removal behaviour of these metals indicated that
      rough solid media with the presence of carbonate were beneficial for the removal
      process. Adsorption and precipitation as metals oxide and probably as metals
      carbonate were among the two mechanisms that contributed to the removal of metals
      from solution.

PMID- 17540557
TI  - Disassembly of lignin and chemical recovery in supercritical water and p-cresol
      mixture. Studies on lignin model compounds.
AB  - The aim of the study was to gain insight into the role of the each unit of lignin
      in the formation of products. Glycerol, guaiacol, the mixture of glycerol and
      guaiacol (Gly&Gua), and guaiacylglycerol-beta-guaiacyl ether (GGGE) were used as
      lignin model compounds to study fragmentation of lignin in an excess of water and
      p-cresol at 400 degrees C. The products have been analyzed employing gas
      chromatography (GC)-mass spectrometer (MS) and gas chromatography-frame
      ionization detector for qualitative and quantitative analysis. GC-MS analysis
      indicated that phenol, o-cresol, methyl-anisole, di-methyl-phenol, ethyl-methyl
      phenol, 2-(hydroxy-benzyl)-4-methyl-phenol (BMP) and 2-(2-hydroxy-5-methyl
      benzyl)-4-methyl-phenol were formed. The products were similar to the products by
      the fragmentation of lignin. The products, except o-cresol, were primarily
      derived from glycerol and/or guaiacol. We also found that the amount of BMP
      derived from GGGE, which has glycerol unit and guaiacol unit in its structure, is
      much more than that derived from Gly&Gua. The increase of the BMP yield by
      reaction with GGGE compared with (glycerol and/or guaiacol) indicates that
      guaiacylglycerol unit with linkage of Gly&Gua plays an important role in the
      formation of BMP and also it is suggested that the BMP formation from GGGE has
      pathways other than that from Gly&Gua.

PMID- 17540558
TI  - Structural and physicochemical characterization of crude biosurfactant produced
      by Pseudomonas aeruginosa SP4 isolated from petroleum-contaminated soil.
AB  - Pseudomonas aeruginosa strain SP4, isolated from petroleum-contaminated soil in
      Thailand, was used to produce a biosurfactant from a nutrient broth with palm oil
      as the carbon source. The key components of the crude biosurfactant were
      fractionated by using HPLC-ELSD technique. With the use of ATR-FTIR spectroscopy,
      in combination with (1)H NMR and MS analyses, chemical structures of the
      fractionated components of the crude biosurfactant were identified as rhamnolipid
      species. When compared to synthetic surfactants, including Pluronic F-68, which
      is a triblock nonionic surfactant containing poly(ethylene oxide) and
      poly(propylene oxide), and sodium dodecyl sulfate, the crude biosurfactant showed
      comparable physicochemical properties, in terms of the surface activities. The
      crude biosurfactant reduced the surface tension of pure water to 29.0 mN/m with a
      critical micelle concentration of approximately 200 mg/l, and it exhibited good
      thermal and pH stability. The crude biosurfactant also formed stable water-in-oil
      microemulsions with crude oil and various types of vegetable oils, but not with
      short-chain hydrocarbons.

PMID- 17540559
TI  - Pectin-rich fruit wastes as biosorbents for heavy metal removal: equilibrium and
      kinetics.
AB  - Biosorption can be used as a cost effective and efficient technique for the
      removal of toxic heavy metals from wastewater. Waste materials from industries
      such as food processing and agriculture may act as biosorbents. This study
      investigates the removal of cadmium by fruit wastes (derived from several citrus
      fruits, apples and grapes). Citrus peels were identified as the most promising
      biosorbent due to high metal uptake in conjunction with physical stability.
      Uptake was rapid with equilibrium reached after 30-80 min depending on the
      particle size (0.18-0.9 mm). Sorption kinetics followed a second-order model.
      Sorption equilibrium isotherms could be described by the Langmuir model in some
      cases, whereas in others an S-shaped isotherm was observed, that did not follow
      the Langmuir isotherm model. The metal uptake increased with pH, with uptake
      capacities ranging between 0.5 and 0.9 meq/g of dry peel. Due to their low cost,
      good uptake capacity, and rapid kinetics, citrus peels are a promising biosorbent
      material warranting further study.

PMID- 17540560
TI  - Structure-based design, synthesis, and study of pyrazolo[1,5-a][1,3,5]triazine
      derivatives as potent inhibitors of protein kinase CK2.
AB  - The structure-based design, synthesis, and anticancer activity of novel
      inhibitors of protein kinase CK2 are described. Using pyrazolo[1,5
      a][1,3,5]triazine as the core scaffold, a structure-guided series of
      modifications provided pM inhibitors with microM-level cytotoxic activity in cell
      based assays with prostate and colon cancer cell lines.

PMID- 17540561
TI  - Carbonic anhydrase activators: activation of the human isoforms VII (cytosolic)
      and XIV (transmembrane) with amino acids and amines.
AB  - An activation study of the human carbonic anhydrase (hCA, EC 4.2.1.1) isozymes
      VII and XIV using a small library of natural/non-natural amino acids and
      aromatic/heterocyclic amines is reported. hCA VII was efficiently activated by L
      /D-His, dopamine and serotonin (K(A)s of 0.71-0.93 microM). The best hCA XIV
      activators were histamine (K(A) of 10 nM), L-Phe, L-/D-His and 4-amino-L-Phe
      (K(A)s of 0.24-2.90 microM). In view of the significant expression levels of CA
      VII and CA XIV in the brain, selective activation of these isoforms may be useful
      when developing pharmacologic agents for the management of major disorders such
      as epilepsy and Alzheimer's disease.

PMID- 17540562
TI  - Synthesis and structure-activity relationship of imidazo(1,2-a)thieno(3,2
      e)pyrazines as IKK-beta inhibitors.
AB  - The identification of a potent series of IKK-beta selective inhibitors based on
      an imidazothienopyrazine template and the oral efficacy of one such analog (22j)
      in the LPS-induced TNF-alpha release mouse model are described.

PMID- 17540563
TI  - Carbonic anhydrase inhibitors: inhibition of human, bacterial, and archaeal
      isozymes with benzene-1,3-disulfonamides--solution and crystallographic studies.
AB  - Three benzene-1,3-disulfonamide derivatives were investigated for their
      interaction with 12 mammalian alpha-carbonic anhydrases (CAs, EC 4.2.1.1), and
      three bacterial/archaeal CAs belonging to the alpha-, beta-, and gamma-CA class,
      respectively. X-ray crystal structure of the three inhibitors in complex with the
      dominant human isozyme CA II revealed a particular binding mode within the
      cavity. The sulfonamide group in meta-position to the Zn(2+)-coordinated
      SO(2)NH(2) moiety was oriented toward the hydrophilic side of the active site
      cleft, establishing hydrogen bonds with His64, Asn67, Gln92, and Thr200. The
      plane of the phenyl moiety of the inhibitors was rotated by 45 degrees and tilted
      by 10 degrees with respect to its most recurrent orientation in other CA II
      sulfonamide complexes.

PMID- 17540564
TI  - WITHDRAWN: A qualitative study looking at the psychosocial implications of
      bilateral prophylactic mastectomy.
AB  - The publisher regrets that this is an accidental duplication of an article that
      has already been published in The Breast, 12 (2003) 1-9, doi:10.1016/S0960
      9776(02)00135-2. The duplicate article has therefore been withdrawn.

PMID- 17540565
TI  - WITHDRAWN: Predicting multidrug resistance-related protein and P-glycoprotein
      expression with technetium-99m tetrofosmin mammoscintigraphy.
AB  - The publisher regrets that this is an accidental duplication of an article that
      has already been published in The Breast, 12 (2003) 58-62, doi:10.1016/S0960
      9776(02)00136-4. The duplicate article has therefore been withdrawn.

PMID- 17540566
TI  - WITHDRAWN: Combined epirubicin and vinorelbine as first-line therapy in
      metastatic breast cancer: a pilot study performed by the Danish Breast Cancer
      Cooperative Group.
AB  - The publisher regrets that this is an accidental duplication of an article that
      has already been published in The Breast, 12 (2003) 42-50, doi:10.1016/S0960
      9776(02)00180-7. The duplicate article has therefore been withdrawn.

PMID- 17540567
TI  - WITHDRAWN: Significance of serum vascular endothelial growth factor, insulin-like
      growth factor-I levels and nitric oxide activity in breast cancer patients.
AB  - The publisher regrets that this is an accidental duplication of an article that
      has already been published in The Breast, 12 (2003) 1-9, doi:10.1016/S0960
      9776(02)00214-X. The duplicate article has therefore been withdrawn.

PMID- 17540568
TI  - Transcriptional rewiring of fungal galactose-metabolism circuitry.
AB  - BACKGROUND: The Leloir-pathway genes encode the enzymatic machinery involved in
      the metabolism of galactose. RESULTS: In the distantly related fungi
      Saccharomyces cerevisiae and Candida albicans, the genes encoding these enzymes
      are syntenically arranged, but the upstream regulatory regions are highly
      divergent. In S. cerevisiae, the Leloir-pathway genes are positively regulated by
      Gal4p acting through the UAS(G) sequence CGG(N(11))CCG. However, in C. albicans,
      the Gal4p and UAS(G) combination is found to regulate genes unrelated to
      galactose metabolism. We identified a palindromic sequence that acts to control
      GAL10 expression in C. albicans in the presence of galactose. This palindrome is
      found upstream of other Leloir-pathway genes in C. albicans, and in the absence
      of other regulatory sequences, activation of expression through this sequence in
      the presence of galactose requires Cph1p, the homolog of the Ste12p transcription
      factor of S. cerevisiae. CONCLUSIONS: Although the cellular process of galactose
      induction of the Leloir pathway is conserved between the two organisms, the
      regulatory circuits achieving the cellular process are completely distinct.

PMID- 17540569
TI  - FT protein acts as a long-range signal in Arabidopsis.
AB  - Plants are sessile organisms and must respond to changes in environmental
      conditions. Flowering time is a key developmental switch that is affected by both
      day length and temperature. Environmental cues are sensed by the leaves while the
      responses occur at the apex, requiring long-range communication within the plant.
      For many years it has been known that leaves exposed to light can trigger the
      floral transition of a darkened shoot, and grafting experiments demonstrated that
      the floral stimulus travels long distances. This mobile signal was later termed
      "florigen," but its nature has been unclear. The gene FLOWERING LOCUS T (FT) is a
      major output of both the photoperiod and the vernalization pathways controlling
      the floral transition. FT protein acts at the shoot apex of the plant in concert
      with a transcription factor, FLOWERING LOCUS D (FD). A fundamental question is
      how FT transcription in the leaves leads to active FT protein at the apex. We
      have uncoupled FT protein movement from its biological function to show that FT
      protein is the mobile signal that travels from the leaves to the apex. To our
      knowledge, FT is the only known protein that serves as a long-range developmental
      signal in plants.

PMID- 17540570
TI  - Export of FT protein from phloem companion cells is sufficient for floral
      induction in Arabidopsis.
AB  - Several endogenous and environmental factors need to be integrated to time the
      onset of flowering. Genetic and molecular analyses, primarily in Arabidopsis
      thaliana and rice, have shown that CONSTANS (CO) and FLOWERING LOCUS T (FT) play
      central roles in photoperiod-dependent flowering. The overall picture is that CO
      acts in the phloem companion cells of leaves and that its main effect is to
      induce FT mRNA in these cells. Surprisingly, FT, a small globular protein of 20
      kDa, interacts at the shoot apex with the bZIP transcription factor FLOWERING
      LOCUS D (FD) to induce downstream targets. Given that green fluorescent protein
      (GFP), which as a monomer is 27 kDa, can be easily exported to sink tissue
      including flowers when expressed in phloem companion cells, the latter finding
      strongly implied that FT protein is the mobile floral-inductive signal. In
      agreement with this hypothesis, an FT-GFP fusion, just like GFP, can be exported
      from the phloem of both rice and Arabidopsis. It has been unknown, however,
      whether mobile FT protein is sufficient for transmitting the flowering signal.
      Here we show that FT mRNA is required in phloem companion cells where it acts
      partially redundant with its paralog TWIN SISTER OF FT (TSF) to induce flowering.
      Furthermore, we have devised a method that uncouples FT mRNA and protein effects
      in vivo. We demonstrate that export of FT protein from phloem companion cells is
      sufficient to induce flowering.

PMID- 17540571
TI  - Aminophospholipid translocase TAT-1 promotes phosphatidylserine exposure during
      C. elegans apoptosis.
AB  - Phospholipids are distributed asymmetrically across the plasma-membrane bilayer
      of eukaryotic cells: Phosphatidylserine (PS), phosphatidylethanolamine, and
      phosphoinositides are predominantly restricted to the inner leaflet, whereas
      phophatidylcholine and sphingolipids are enriched on the outer leaflet [1, 2].
      Exposure of PS on the cell surface is a conserved feature of apoptosis and plays
      an important role in promoting the clearance of apoptotic cells by phagocytosis
      [3]. However, the molecular mechanism that drives PS exposure remains mysterious.
      To address this issue, we studied cell-surface changes during apoptosis in the
      nematode C. elegans. Here, we show that PS exposure can readily be detected on
      apoptotic C. elegans cells. We generated a transgenic strain expressing a
      GFP::Annexin V reporter to screen for genes required for this process. Although
      none of the known engulfment genes was required, RNAi knockdown of the putative
      aminophospholipid transporter gene tat-1 abrogated PS exposure on apoptotic
      cells. tat-1(RNAi) also reduced the efficiency of cell-corpse clearance,
      suggesting that PS exposure acts as an "eat-me" signal in worms. We propose that
      tat-1 homologs might also play an important role in PS exposure in mammals.

PMID- 17540572
TI  - Responses to lightness variations in early human visual cortex.
AB  - Lightness is the apparent reflectance of a surface, and it depends not only on
      the actual luminance of the surface but also on the context in which the surface
      is viewed [1-10]. The cortical mechanisms of lightness processing are largely
      unknown, and the role of early cortical areas is still a matter of debate [11
      17]. We studied the cortical responses to lightness variations in early stages of
      the human visual system with functional magnetic resonance imaging (fMRI) while
      observers were performing a demanding fixation task. The set of dynamically
      presented visual stimuli included the rectangular version of the classic Craik
      O'Brien stimulus [3, 18, 19] and a variant that led to a weaker lightness effect,
      as well as a pattern with actual luminance variations. We found that the cortical
      activity in retinotopic areas, including the primary visual cortex (V1), is
      correlated with context-dependent lightness variations.

PMID- 17540573
TI  - A receptor-like kinase mediates the response of Arabidopsis cells to the
      inhibition of cellulose synthesis.
AB  - BACKGROUND: A major challenge is to understand how the walls of expanding plant
      cells are correctly assembled and remodeled, often in the presence of wall
      degrading micro-organisms. Plant cells, like yeast, react to cell-wall
      perturbations as shown by changes in gene expression, accumulation of ectopic
      lignin, and growth arrest caused by the inhibition of cellulose synthesis.
      RESULTS: We have identified a plasma-membrane-bound receptor-like kinase
      (THESEUS1), which is present in elongating cells. Mutations in THE1 and
      overexpression of a functional THE1-GFP fusion protein did not affect wild-type
      (WT) plants but respectively attenuated and enhanced growth inhibition and
      ectopic lignification in seedlings mutated in cellulose synthase CESA6 without
      influencing the cellulose deficiency. A T-DNA insertion mutant for THE1 also
      attenuated the growth defect and ectopic-lignin production in other but not all
      cellulose-deficient mutants. The deregulation of a small number of genes in cesA6
      mutants depended on the presence of THE1. Some of these genes are involved in
      pathogen defense, in wall crosslinking, or in protecting the cell against
      reactive oxygen species. CONCLUSIONS: The results show that THE1 mediates the
      response of growing plant cells to the perturbation of cellulose synthesis and
      may act as a cell-wall-integrity sensor.

PMID- 17540574
TI  - Learning from practice--reflections on a critical incident.
AB  - Reflective practice is considered not only as a valuable tool for providing
      appropriate levels of care but also as an important prerequisite for the
      provision of professional nursing. Indeed, there appears to be consensus in the
      literature that reflections have the potential to assist practitioners to tap
      into knowledge gained from experience and connect theory to practice. However,
      evidence suggests that nurses, including emergency nurses, neglect reflective
      techniques. This paper outlines how the processes of reflection led to one
      emergency nurse developing new insights and understandings on nursing practice.

PMID- 17540575
TI  - Analysis of crucial structural requirements of 2-substituted pyrimido[4,5
      b][1,5]oxazocines as NK(1) receptor antagonist by axially chiral derivatives.
AB  - This study aimed to identify the crucial structural features of 2-substituted 8
      methylpyrimido[4,5-b][1,5]oxazocine derivatives. Axially chiral 8
      methylpyrimido[4,5-b][1,5]oxazocines bearing a substituent at the C-2 position
      were synthesized and evaluated as NK(1) antagonists. The results revealed that
      (aR, 8S)-stereochemistry and the substituent at the C-2 position are important
      for NK(1) receptor recognition.

PMID- 17540576
TI  - Structure and analysis of FCHo2 F-BAR domain: a dimerizing and membrane
      recruitment module that effects membrane curvature.
AB  - A spectrum of membrane curvatures exists within cells, and proteins have evolved
      different modules to detect, create, and maintain these curvatures. Here we
      present the crystal structure of one such module found within human FCHo2. This F
      BAR (extended FCH) module consists of two F-BAR domains, forming an intrinsically
      curved all-helical antiparallel dimer with a Kd of 2.5 microM. The module binds
      liposomes via a concave face, deforming them into tubules with variable diameters
      of up to 130 nm. Pulse EPR studies showed the membrane-bound dimer is the same as
      the crystal dimer, although the N-terminal helix changed conformation on membrane
      binding. Mutation of a phenylalanine on this helix partially attenuated narrow
      tubule formation, and resulted in a gain of curvature sensitivity. This structure
      shows a distant relationship to curvature-sensing BAR modules, and suggests how
      similar coiled-coil architectures in the BAR superfamily have evolved to expand
      the repertoire of membrane-sculpting possibilities.

PMID- 17540577
TI  - Targeting mTOR signaling in lung cancer.
AB  - Lung cancer is the leading cause of cancer-related mortality in the world, with
      more than 1 million deaths per year. Over the past years, lung cancer treatment
      has been based on cytotoxic agents and an improvement in the outcome and quality
      of life for patients has been observed. However, it has become clear that
      additional therapeutic strategies are urgently required in order to provide an
      improved survival benefit for patients. Two major intracellular signaling
      pathways, the Ras/Raf/extracellular signal-regulated kinase (Erk) and the
      phosphoinositide 3-kinase (PI3K)/Akt pathways have been extensively studied in
      neoplasia, including lung cancer. Furthermore, the study of constitutively
      activated receptor tyrosine kinases (RTKs) and their downstream signaling
      mediators has opened a promising new field of investigation for lung cancer
      treatment. Since both the Ras/Raf/Erk and the PI3K/Akt pathways are downstream of
      a plethora of activated RTKs, they have been extensively studied for the
      development of novel anti-tumor agents. Moreover, the mammalian target of
      rapamycin (mTOR) has been identified as a downstream target of the PI3K/Akt
      pathway. Rapamycin and its derivatives are highly selective and very potent
      inhibitors of mTOR and initial pre-clinical and clinical studies have reported
      encouraging results for different tumor types. Nevertheless for lung cancer, this
      approach has not been successful yet. Here we will review the molecular basis of
      PI3K/Akt/mTOR signaling in lung cancer and further discuss the therapeutic
      potential of multi-targeted strategies involving mTOR inhibitors.

PMID- 17540578
TI  - Upregulation of tumor necrosis factor-alpha expression by trans10-cis12
      conjugated linoleic acid enhances phagocytosis of RAW macrophages via a
      peroxisome proliferator-activated receptor gamma-dependent pathway.
AB  - The aim of this study was to examine whether tumor necrosis factor (TNF)-alpha
      expression in the phagocytic activity of RAW macrophages by trans10-cis12 (10t
      12c) conjugated linoleic acid (CLA) is associated with peroxisome proliferator
      activated receptor gamma (PPARgamma) activation. 10t-12c CLA induced the TNF
      alpha expression in RAW macrophages. Phagocytic activity of naive RAW macrophages
      was increased either by recombinant mouse (rm) TNF-alpha or by culture
      supernatant from 10t-12c CLA-treated RAW macrophages. This phagocytic activity
      was inhibited by addition of anti-rmTNF-alpha polyclonal antibody (pAb). 10t-12c
      CLA also increased the level of PPARgamma protein and mRNA in RAW macrophages.
      When naive RAW macrophages were incubated with the culture supernatant from RAW
      macrophages treated with 10t-12c CLA plus GW 9662, a PPARgamma antagonist, their
      phagocytic activity was significantly inhibited. In addition, GW 9662 antagonized
      the effect of 10t-12c CLA in stimulating TNF-alpha expression. These results
      suggest that 10t-12c CLA modulates the phagocytic activity of RAW macrophages by
      upregulating TNF-alpha expression via a PPARgamma-dependent pathway.

PMID- 17540579
TI  - A mutation in human VAP-B--MSP domain, present in ALS patients, affects the
      interaction with other cellular proteins.
AB  - Amyotrophic Lateral Sclerosis (ALS) is the most common adult-onset Motor Neuron
      Disease (MND), characterized by motor neurons death in the cortex, brainstem and
      spinal cord. Ten loci linked to Familial ALS have been mapped. ALS8 is caused by
      a substitution of a proline by a serine in the Vesicle-Associated Membrane
      Protein-Associated protein-B/C (VAP-B/C). VAP-B belongs to a highly conserved
      family of proteins implicated in Endoplasmic Reticulum-Golgi and intra-Golgi
      transport and microtubules stabilization. Previous studies demonstrated that the
      P56S mutation disrupts the subcellular localization of VAP-B and that this
      position would be essential for Unfolded Protein Response (UPR) induced by VAP-B.
      In the present work we expressed and purified recombinant wild-type and P56S
      mutant VAP-B-MSP domain for the analysis of its interactions with other cellular
      proteins. Our findings suggest that the P56S mutation may lead to a less stable
      interaction of this endoplasmic reticulum protein with at least two other
      proteins: tubulin and GAPDH. These two proteins have been previously related to
      other forms of neurodegenerative diseases and are potential key points to
      understand ALS8 pathogenesis and other forms of MND. Understanding the role of
      these protein interactions may help the treatment of this devastating disease in
      the future.

PMID- 17540580
TI  - Cloning and structural analysis of Mycobacterium leprae serine
      hydroxymethyltransferase.
AB  - Serine hydroxymethyltransferase (SHMT) plays a key role in cell physiology as it
      participates in the different interconversion pathway of folate coenzymes,
      provides almost exclusively folate one carbon fragments for the biosynthesis of a
      variety of end products. For the first time, Mycobacterium leprae glyA gene,
      encodes the enzyme serine hydroxymethyltransferase, has been cloned in
      Escherichia coli, over-expressed and purified the protein product (mlSHMT) for
      folding and stability studies under various denaturating conditions. The
      recombinant mlSHMT exists as homo-dimer of molecular mass about 90 kDa under
      physiological conditions . The studies on catalytic properties of mlSHMT show
      that the enzyme catalyzes the H(4)-folate dependent retro-aldol cleavage of L
      serine, however, D-alanine dependent transaminase activity was absent in the
      enzyme. Further analysis of the enzyme kinetics for hydroxymethyltransferase
      reaction for mlSHMT demonstrates a comparable K(m) value for L-serine to SHMTs
      from other sources but significantly lower catalytic efficiency (k(cat)/K(m)).
      The mlSHMT is resistant to alkaline denaturation and exist as apo-dimer up to pH
      10.5. Urea and guanidinium chloride induces dissociation of mlSHMT dimer into
      monomer at low denaturant concentrations, and leads to loss of enzymatic
      activity.

PMID- 17540581
TI  - Episodic future thought and its relation to remembering: evidence from ratings of
      subjective experience.
AB  - The goal of the present study was to examine the hypothesis that the ability to
      construct vivid mental images of the future involves sampling the contents of
      memory. In two experiments, participants envisioned future scenarios occurring in
      contextual settings that were represented in memory in varying degrees of
      perceptual detail. In both experiments, detailed contextual settings were
      associated with more detailed images of the future and a stronger subjective
      experience. Our findings suggest that the contents of memory are routinely
      sampled during the construction of personal future scenarios.

PMID- 17540582
TI  - One-trial conditioning of aerial respiratory behaviour in Lymnaea stagnalis.
AB  - Repeated spaced training sessions of contingent tactile stimulation to the
      pneumostome as it opens are required to cause long-term memory (LTM) formation of
      aerial respiratory behaviour making if difficult to determine exactly when memory
      forms. We have devised a single-trial aversive operant conditioning training
      procedure in Lymnaea to be better able to elucidate the causal mechanisms of LTM
      formation. Observations of baseline breathing behaviour in hypoxia were first
      made. Twenty-four hours later the snails were trained using the single trial
      procedure, by placing them in a small Petri dish containing 4 ml of 25 mM KCl for
      30-35s as soon as the first pneumostome opening in hypoxia was attempted. LTM was
      present if (1) breathing behaviour following training was significantly less than
      before; and (2) breathing behaviour post-training was significantly less in
      experimental groups than in yoked control groups. LTM persisted for 24 h but not
      48 h. Yoked controls that received an aversive stimulus not contingent with
      pneumostome opening had no evidence of memory. Cooling directly after, but not at
      any other time, blocks LTM formation. LTM formation was also prevented by removal
      of the cell body of the neuron RPeD1 before training.

PMID- 17540583
TI  - Distinct ventral and dorsal hippocampus AP5 anxiolytic effects revealed in the
      elevated plus-maze task in rats.
AB  - The hippocampal formation (HPC) mediates processes associated with learning,
      memory, anxiety and fear. The glutamate N-methyl-d-aspartate (NMDA)-receptor
      subtype is involved in many HPC functional processes related to learning and
      memory. Although not tested for the HPC, NMDA-receptor antagonists reduced fear
      and anxiety related responses when applied to other brain regions mediating
      defensive behaviour. Consequently, this study evaluated the effects of ventral or
      dorsal HPC application of the NMDA-receptor antagonist, AP5, in rats submitted to
      the Trial 1/Trial 2 elevated plus-maze (EPM) task. Ventral, but not dorsal,
      infusions of AP5 (6 and 24 nmol) before EPM Trial 1 increased open arms
      exploration and reduced risk assessment behavior, suggesting an anxiolytic-like
      effect. Furthermore, no interference in the avoidance responses was detected
      during EPM Trial 2 after AP5 infusion into the ventral or dorsal HPC before Trial
      1, post-trial 1, or before Trial 2. These data support the notion of differential
      involvement of ventral HPC, but not dorsal, in mechanisms associated with anxiety
      and suggest the participation of the glutamatergic transmission, through NMDA
      receptor, into the ventral HPC in the mediation of defensive behavior.

PMID- 17540584
TI  - Basolateral amygdala noradrenergic activity is involved in the acquisition of
      conditioned odor aversion in the rat.
AB  - Conditioned odor aversion (COA) is the avoidance of an odorized-tasteless
      solution (the conditioned stimulus, CS), the ingestion of which precedes
      toxicosis. Previous works have shown that the basolateral nucleus of the amygdala
      (BLA) is involved in the acquisition, and more precisely, the control of the CS
      memory trace, of COA. Since catecholamine depletion of the amygdala induced a
      deficit in the potentiated version of COA, this study investigated the role of
      the adrenergic system in the BLA during COA. Male Wistar rats bilaterally
      implanted with cannulae aimed at the BLA were microinjected with the beta
      adrenergic antagonist propranolol (1 microg/0.2 microl) during the acquisition (5
      min before the CS presentation, pre-CS, or immediately after, post-CS) or during
      the retrieval test (5 min before test, pre-test). Results showed that pre-CS, but
      neither post-CS nor pre-test, infusions of propranolol impaired COA, suggesting
      that beta-adrenergic system activity in the BLA is involved in the acquisition
      but not the expression of COA. Moreover, the fact that pre-CS, but not post-CS,
      treatment disrupted COA suggests that beta-adrenergic system in the BLA is
      involved in the initiation but not the maintenance of the CS memory trace during
      COA acquisition.

PMID- 17540585
TI  - Acquisition of murine NK cell cytotoxicity requires the translation of a pre
      existing pool of granzyme B and perforin mRNAs.
AB  - Although activated murine NK cells can use the granule exocytosis pathway to kill
      target cells immediately upon recognition, resting murine NK cells are minimally
      cytotoxic for unknown reasons. Here, we showed that resting NK cells contained
      abundant granzyme A, but little granzyme B or perforin; in contrast, the mRNAs
      for all three genes were abundant. Cytokine-induced in vitro activation of NK
      cells resulted in potent cytotoxicity associated with a dramatic increase in
      granzyme B and perforin, but only minimal changes in mRNA abundance for these
      genes. The same pattern of regulation was found in vivo with murine
      cytomegalovirus infection as a physiologic model of NK cell activation. These
      data suggest that resting murine NK cells are minimally cytotoxic because of a
      block in perforin and granzyme B mRNA translation that is released by NK cell
      activation.

PMID- 17540586
TI  - Co-adhesion and biofilm formation by Fusobacterium nucleatum in response to
      growth pH.
AB  - Fusobacterium nucleatum is a Gram-negative anaerobic organism considered to play
      an important role in the progression of periodontal disease and is commonly found
      in clinical infections of other body sites. Apart from its metabolic versatility,
      its cell-surface properties enable it to attach to epithelial cells, collagen,
      gingival epithelial cells and other bacterial genera, but not with other
      Fusobacteria. The development of periodontitis is associated with a rise in pH in
      the gingival sulcus to around 8.5, and this is thought to occur by the catabolism
      of proteins supplied by gingival crevicular fluid. F. nucleatum is commonly
      isolated from diseased sites and has also been shown to survive in root canal
      systems at pH 9.0 after Ca(OH)(2) treatment. In order to survive hostile
      environmental conditions, such as nutrient deprivation and fluctuating
      temperature and pH, bacteria form biofilms, which are usually made up of multi
      species co-aggregates. We have grown F. nucleatum in a chemostat at a growth rate
      consistent with that of oral bacteria in vivo and report that, at a growth pH of
      8.2, F. nucleatum co-adheres and forms a homogeneous biofilm. Cell-surface
      hydrophobicity was determined in planktonic and co-adhering cells to characterise
      the interfacial interactions associated with the response to pH. Cell-surface
      hydrophobicity was found to increase at pH 8.2 and this was also associated with
      a decrease in the levels of intracellular polyglucose (IP) and an observed change
      in the bacterial cell morphology. To our knowledge, these results represent the
      first study in which F. nucleatum has been shown to co-adhere and form a biofilm,
      which may be important in the organism's persistence during the transition from
      health to disease in vivo.

PMID- 17540587
TI  - Induction and transcription of VSH-1, a prophage-like gene transfer agent of
      Brachyspira hyodysenteriae.
AB  - The anaerobic spirochete Brachyspira hyodysenteriae is host to a bacteriophage
      like agent known as VSH-1. VSH-1 is a novel gene transfer mechanism which does
      not self-propagate and transfers random 7.5kb fragments of host DNA between B.
      hyodysenteriae cells. In these investigations early events during VSH-1 induction
      by mitomycin C were examined. Quantitative PCR analysis revealed that VSH-1 hvp38
      and hvp53 genes did not detectably increase in copy numbers during induction.
      Based on Northern blot hybridization assays, transcription of VSH-1 genes hvp38,
      hvp53, hvp45, hvp101, and lys increased fivefold to tenfold between 2 and 4h
      after induction whereas mRNA levels for B. hyodysenteriae flaA1 declined over the
      same time period. Chloramphenicol prevented the mitomycin C-induced increases in
      VSH-1 gene transcription. Hydrogen peroxide (300muM) substituted for mitomycin C
      as an inducer of VSH-1 gene transcription and is a possible 'natural' inducer of
      VSH-1 production in vivo. Northern blot hybridization, RT PCR, and primer
      extension analyses showed that VSH-1 genes are co-transcribed at an initiation
      site upstream of the VSH-1 gene operon. Two direct heptanucleotide repeats
      (ACTTATA) were identified between the putative -35 and -10 positions of the VSH-1
      gene operon and are likely to represent a binding site for transcription
      proteins. These findings indicate VSH-1 virion production does not require genome
      replication, consistent with the inability of VSH-1 to self-propagate. Early
      events in VSH-1 induction include de novo synthesis of protein(s) essential for
      transcription of VSH-1 genes as polycistronic mRNA initiating upstream of the
      hvp45 gene.

PMID- 17540588
TI  - Medical management of abdominal aortic aneurysm.
AB  - Medical management of patients with abdominal aortic aneurysm (AAA) is required
      for several different reasons. Since these patients have an increased risk of
      cardiovascular death therapy to reduce cardiovascular events is essential.
      Treatment is in line with the medical management of coronary artery disease
      including smoking cessation, statins and anti-platelet therapy. Some of these
      therapies also will slow aneurysm growth. Currently there is no proven focused
      therapy that reduces aneurysm growth, but the emerging strategies are discussed.
      Medical management also is required to reduce peri-operative risks and stabilise
      endovascular aneurysm repair. Whilst some of the therapies targeting
      cardiovascular risk reduction may be helpful, other emerging strategies are
      discussed.

PMID- 17540589
TI  - Iron storage disease: facts, fiction and progress.
AB  - There are many forms of iron storage disease, some hereditary and some acquired.
      The most common of the hereditary forms is HFE-associated hemochromatosis, and it
      is this disorder that is the main focus of this presentation. The body iron
      content is regulated by controlling absorption, and studies in the past decade
      have clarified, in part, how this regulation functions. A 25-amino-acid peptide
      hepcidin is up-regulated by iron and by inflammation, and it inhibits iron
      absorption and traps iron in macrophages by binding to and causing degradation of
      the iron transport protein ferroportin. Most forms of hemochromatosis results
      from dysregulation of hepcidin or defects of hepcidin or ferroportin themselves.
      Hereditary hemochromatosis was once considered to be very rare, but in the 1970s
      and 1980s, with the introduction of better diagnostic tests, it was considered
      the most common disease among Europeans. Controlled epidemiologic studies carried
      out in the last decade have shown, however, the disease itself actually is rare,
      and only its genotype and associated biochemical changes that are common. We do
      not understand why only a few homozygotes develop severe disease. It now seems
      unlikely that there are important modifying genes, and although alcohol is known
      to have some effect, excess drinking probably plays only a modest role in
      determining the hemochromatosis phenotype. Hereditary hemochromatosis is readily
      treated by phlebotomy. Secondary forms of the disease require chelation therapy,
      and the recent introduction of effective oral chelating agents is an important
      step forward in treating patients with disorders in which iron overload often
      proves to be fatal, such as thalassemia, myelodysplastic anemias, and
      dyserythropoietic anemias. While much has been learned about the regulation of
      iron homeostasis in the past decade, many mysteries remain and represent
      challenges that will keep us occupied for years to come.

PMID- 17540590
TI  - Alpha fetoprotein is increasing with age in ataxia-telangiectasia.
AB  - The elevated serum alpha fetoprotein (AFP) concentration in ataxia-telangiectasia
      (A-T) patients has been known for decades, but the individual variation of AFP
      levels over time has not been studied. We have followed 12 patients (five girls
      and seven boys) for 1-12 years (mean 5.5 years) measuring in each patient AFP 2-8
      (mean 4) times. Serum AFP levels were increased in all patients, mean 168.7
      (range 40-373) kU/L, and without significant differences between the patients.
      There was a significant age related difference in the serum AFP level. A positive
      linear relationship (r=0.61, p=0.04) could be found between AFP level and age.
      Albumin levels were within normal range and did not change with age. Four
      patients had slightly increased aspartate aminotransferase (AST) levels. None of
      the patients had serological evidence of infectious hepatitis, and none had
      increased levels of carcinoembryonic antigen. Repeated standardized observations
      of gait function revealed no major difference in neurological deterioration
      between our patients. All had classical A-T disease and mainly truncating
      mutations; 21 out of 24 possible mutations were either frameshift or nonsense.
      Four were homozygous for the Norwegian ATM founder mutation. No correlation
      between serum AFP levels and the different ATM genotypes could be found. We
      conclude that serum AFP is not only elevated, but also is continuously increasing
      with age in patients with classical A-T disease.

PMID- 17540591
TI  - A theoretical study on protonation of some halogen substituted pyridine
      derivatives.
AB  - The geometries of 12 multi-halogenated pyridine derivatives were optimized using
      theoretical methods. The Hartree-Fock (HF) method with the 6-31G(d) and B3LYP
      method with 6-31G(d) basis sets were found to be adequate in calculation of
      absolute acidity constants, pK(a) values. A perfect correlation between the
      computed and experimentally obtained acidity constants, pK(a) values, was
      observed.

PMID- 17540592
TI  - Expression of the small heat shock protein gene, hsp30, in Rana catesbeiana
      fibroblasts.
AB  - In the present study, we examined the expression of the Rana catesbeiana small
      heat shock protein gene, hsp30, in an FT fibroblast cell line. Northern and
      western blot analyses revealed that hsp30 mRNA or HSP30 protein was not present
      constitutively but was strongly induced at a heat shock temperature of 35 degrees
      C. However, treatment of FT cells with sodium arsenite at concentrations that
      induced hsp gene expression in other amphibian systems caused cell death. Non
      lethal concentrations of sodium arsenite (10 microM) induced only minimal
      accumulation of hsp30 mRNA or protein after 12 h. Immunocytochemical analyses
      employing laser scanning confocal microscopy detected the presence of heat
      inducible HSP30, in a granular or punctate pattern. HSP30 was enriched in the
      nucleus with more diffuse localization in the cytoplasm. The nuclear localization
      of HSP30 was more prominent with continuous heat shock. These heat treatments did
      not alter FT cell shape or disrupt actin cytoskeletal organization. Also, HSP30
      did not co-localize with the actin cytoskeleton.

PMID- 17540593
TI  - Acute toxicity of ammonia and its effects on the haemolymph osmolality, ammonia
      N, pH and ionic composition of early juvenile mud crabs, Scylla serrata
      (Forskal).
AB  - The current study was conducted to determine the LC(50) value of ammonia-N as
      well as the effects of acute exposure to elevated ammonia on the haemolymph
      osmolality, ionic composition, ammonia-N and pH levels of early juvenile mud
      crabs, Scylla serrata. The results show that early S. serrata juveniles have a
      high 96-h LC(50) value of 95.35 mg/L ammonia-N (6.81 mg/L NH(3)-N) or 6.80 mmol/L
      total ammonia-N (0.486 mmol/L NH(3)-N). Following a 96-h exposure, the haemolymph
      osmolality and K(+) levels of the surviving crabs remained unaltered (p>0.05) at
      all ammonia-N concentrations, while the haemolymph Na(+) and Ca(2+) were
      significantly lower (p<0.05) for the crabs exposed to 5.710 and 7.138 mmol/L
      ammonia-N. While the haemolymph ammonia-N levels of the crabs significantly
      increased (p<0.01) with increasing external ammonia-N concentrations, the
      haemolymph ammonia-N of the crabs remained below the external ammonia-N
      concentrations. The haemolymph pH of the crabs significantly increased between
      0.714 and 4.283 mmol/L total ammonia-N. However, at 5.710 mmol/L total ammonia-N
      the haemolymph pH dropped and was not significantly different (p>0.05) from that
      of the control crabs which coincided with significantly lower (p<0.05) haemolymph
      Na(+) and Ca(2+) levels. These physiological responses may explain the high
      ammonia tolerance of early S. serrata juveniles.

PMID- 17540594
TI  - IGF-I, IGFBP-3 and ALS generation test in Turner syndrome.
AB  - OBJECTIVES: The pathophysiology of the short stature in girls with Turner
      syndrome (TS) is not well understood. The "IGF-I generation test" is used to
      assess the sensitivity to growth hormone. We compared the biochemical response to
      four days of growth hormone of TS and controls. STUDY DESIGN: Pre-pubertal TS
      were recruited to participate in the study. Their siblings served as controls.
      IGF-I, IGFBP-3 and ALS were measured before and 5 days after using hGH
      (0.05mg/kg/day). Student-t test was used to compare the differences in their
      responses. RESULTS: Eleven TS (mean age of 8.5+/-2.4) and 11 siblings (6 females
      and 5 males) (mean age of 7.0+/-2.0) participated in the study. The basal serum
      levels of IGF-I, IGFBP-3 and ALS were normal and not different between groups
      (p=0.62 for IGF-I, p=0.91 for IGFBP-3 and p=0.51 for ALS). The IGF-I generation
      test was positive in all controls and in 10/11 TS. The IGFBP-3 generation test
      was positive in 6/11 controls and 4/11 TS. After hGH the mean IGFBP-3 was lower
      in TS than in controls (p=0.08). The ALS response to hGH was not uniform between
      groups. CONCLUSIONS: The IGF-I and ALS generation test results were not different
      between controls and TS. The IGFBP-3 results were higher in the control group but
      more than 50% of tested children did not pass. The IGF-I/IGFBP-3 generation
      tests, as presently done, did not help in the understanding of the short stature
      in TS. The use of different GH dosages and number of doses need to be
      investigated.

PMID- 17540595
TI  - Equine biochemical multiple acyl-CoA dehydrogenase deficiency (MADD) as a cause
      of rhabdomyolysis.
AB  - Two horses (a 7-year-old Groninger warmblood gelding and a six-month-old
      Trakehner mare) with pathologically confirmed rhabdomyolysis were diagnosed as
      suffering from multiple acyl-CoA dehydrogenase deficiency (MADD). This disorder
      has not been recognised in animals before. Clinical signs of both horses were a
      stiff, insecure gait, myoglobinuria, and finally recumbency. Urine, plasma, and
      muscle tissues were investigated. Analysis of plasma showed hyperglycemia, lactic
      acidemia, increased activity of muscle enzymes (ASAT, LDH, CK), and impaired
      kidney function (increased urea and creatinine). The most remarkable findings of
      organic acids in urine of both horses were increased lactic acid, ethylmalonic
      acid (EMA), 2-methylsuccinic acid, butyrylglycine (iso)valerylglycine, and
      hexanoylglycine. EMA was also increased in plasma of both animals. Furthermore,
      the profile of acylcarnitines in plasma from both animals showed a substantial
      elevation of C4-, C5-, C6-, C8-, and C5-DC-carnitine. Concentrations of
      acylcarnitines in urine of both animals revealed increased excretions of C2-, C3
      , C4-, C5-, C6-, C5-OH-, C8-, C10:1-, C10-, and C5-DC-carnitine. In addition,
      concentrations of free carnitine were also increased. Quantitative biochemical
      measurement of enzyme activities in muscle tissue showed deficiencies of short
      chain acyl-CoA dehydrogenase (SCAD), medium-chain acyl-CoA dehydrogenase (MCAD),
      and isovaleryl-CoA dehydrogenase (IVD) also indicating MADD. Histology revealed
      extensive rhabdomyolysis with microvesicular lipidosis predominantly in type 1
      muscle fibers and mitochondrial damage. However, the ETF and ETF-QO activities
      were within normal limits indicating the metabolic disorder to be acquired rather
      than inherited. To our knowledge, these are the first cases of biochemical MADD
      reported in equine medicine.

PMID- 17540596
TI  - Chemical chaperone rescue of mutant human cystathionine beta-synthase.
AB  - Missense mutations in the cystathionine beta-synthase (CBS) gene, such as I278T,
      are responsible for CBS deficiency, the most common inherited disorder in sulfur
      metabolism. Expression of human mutant CBS proteins in Saccharomyces cerevisiae
      reveals that most disease causing mutations severely inhibit enzyme activity and
      cannot support growth of yeast on cysteine-free media. Here, we show that the
      osmolyte chemical chaperones glycerol, trimethylamine-N-oxide, dimethylsulfoxide,
      proline or sorbitol, when added to yeast media, allows growth on cysteine-free
      media and causes increased enzyme activity from I278T and three other mutant CBS
      proteins. Rescuable mutants are ones that are predicted to cause a decrease in
      solvent accessible surface area. The increase in enzyme activity is associated
      with stabilization of the tetramer form of the enzyme. This effect is not
      specific to yeast, as addition of the chaperone glycerol resulted in increased
      I278T activity when the enzyme is produced either in Escherichia coli or in a
      coupled in vitro transcription/translation reaction. However, no stimulation of
      specific activity was observed when chaperones were added directly to purified
      I278T indicating that the presence of chemical chaperones is required during
      translation. We also found that by mixing different chaperones we could achieve
      rescue at significantly lower chaperone concentrations. Taken together, our data
      show that chemical chaperones present during the initial folding process can
      facilitate proper folding of several mutant CBS proteins and suggest it may be
      possible to treat some inborn errors of metabolism with agents that enhance
      proper protein folding.

PMID- 17540597
TI  - Muscular glycogen storage diseases without increased glycogen content on
      histopathological examination.
AB  - Histopathological findings of muscle biopsies from five patients with two
      different muscular glycogen storage diseases (mGSD) were presented. From these
      investigations it emerged that the yield of histopathology in mGSD is low. In
      only one of five patients histopathological findings gave a clue towards
      diagnosis. It can be concluded that non-specific findings or even normal
      appearance of a muscle biopsy does not exclude mGSD.

PMID- 17540598
TI  - Transcriptional activation of miR-34a contributes to p53-mediated apoptosis.
AB  - p53 is a potent tumor suppressor, whose biological effects are largely due to its
      function as a transcriptional regulator. Here we report that, in addition to
      regulating the expression of hundreds of protein-coding genes, p53 also modulates
      the levels of microRNAs (miRNAs). Specifically, p53 can induce expression of
      microRNA-34a (miR-34a) in cultured cells as well as in irradiated mice, by
      binding to a perfect p53 binding site located within the gene that gives rise to
      miR-34a. Processing of the primary transcript into mature miR-34a involves the
      excision of a 30 kb intron. Notably, inactivation of miR-34a strongly attenuates
      p53-mediated apoptosis in cells exposed to genotoxic stress, whereas
      overexpression of miR-34a mildly increases apoptosis. Hence, miR-34a is a direct
      proapoptotic transcriptional target of p53 that can mediate some of p53's
      biological effects. Perturbation of miR-34a expression, as occurs in some human
      cancers, may thus contribute to tumorigenesis by attenuating p53-dependent
      apoptosis.

PMID- 17540600
TI  - An aberrant high prevalence of hepatitis B infection among Afghans residing in
      one of the Bushehr refugee camps (Dalaki camp) in the southwest of Iran.

PMID- 17540599
TI  - Transactivation of miR-34a by p53 broadly influences gene expression and promotes
      apoptosis.
AB  - The p53 tumor suppressor protein is a critical regulator of the cellular response
      to cancer-initiating insults such as genotoxic stress. In this report, we
      demonstrate that microRNAs (miRNAs) are important components of the p53
      transcriptional network. Global miRNA expression analyses identified a cohort of
      miRNAs that exhibit p53-dependent upregulation following DNA damage. One such
      miRNA, miR-34a, is commonly deleted in human cancers and, as shown here,
      frequently absent in pancreatic cancer cells. Characterization of the miR-34a
      primary transcript and promoter demonstrates that this miRNA is directly
      transactivated by p53. Expression of miR-34a causes dramatic reprogramming of
      gene expression and promotes apoptosis. Much like the known set of p53-regulated
      genes, miR-34a-responsive genes are highly enriched for those that regulate cell
      cycle progression, apoptosis, DNA repair, and angiogenesis. Therefore, it is
      likely that an important function of miR-34a is the modulation and fine-tuning of
      the gene expression program initiated by p53.

PMID- 17540601
TI  - Influenza and the Hajj: defining influenza-like illness clinically.

PMID- 17540602
TI  - Manufacture of plasma-derived products in France and measures to prevent the risk
      of vCJD transmission: precautionary measures and efficacy of manufacturing
      processes in prion removal.
AB  - The emergence of the variant Creutzfeldt-Jakob disease in the mid 1990s soon
      raised concerns about its possible transmission through the use of blood and
      plasma-derived medicinal products. A risk analysis approach was initiated by
      health authorities, based on updated scientific knowledge and precautionary
      measures were implemented in France and other countries for the management of
      this new possible risk. Assessment of the vCJD risk is based on epidemiology and
      estimates of the number of potential cases in the future, on blood infectivity
      data from models of transmissible spongiform encephalopathies and on data from
      studies of the capacity of manufacturing processes to remove the agent, should it
      be present in the plasma of infected donors. The transmission of vCJD by non
      leukocyte-depleted labile blood components has recently been confirmed. There
      have been no reports of cases associated with the use of plasma-derived products
      and the scientific data, and risk analyses for those plasma products, which are
      of the greatest therapeutic interest, support their safety with respect to this
      transmission risk. The precautionary measures applied in France and the data
      contributing to the risk assessment of plasma products are reviewed and updated
      in the present paper. The uncertainties, which remain, are also addressed and
      discussed, as well as the ongoing research and developments in this area.

PMID- 17540603
TI  - Intranasal immunisation with recombinant Lactococcus lactis displaying either
      anchored or secreted forms of Proteus mirabilis MrpA fimbrial protein confers
      specific immune response and induces a significant reduction of kidney bacterial
      colonisation in mice.
AB  - Proteus mirabilis, a common cause of urinary tract infections in humans, can
      express different fimbriae. MR/P fimbriae may contribute to bacterial
      colonisation, and its structural protein MrpA represents a promising candidate
      antigen for mucosal vaccination. Commercial complex vaccines have limited, short
      lived protection and are incapable of eliciting mucosal responses against
      putative antigens related to virulence. The development of mucosal live vaccines
      using food-grade lactic acid bacterium Lactococcus lactis as antigen vehicle is
      an attractive alternative and a safe vaccination strategy against P. mirabilis
      infection. Here, we report the construction of L. lactis strains modified to
      produce MrpA via two cellular locations, cell wall-anchored and secreted.
      Protection assays against P. mirabilis infection and evaluation of the immune
      response generated after immunisation were conducted in a mouse model. MrpA
      protein was efficiently expressed by L. lactis strain and caused a significant
      induction of specific serum IgG and IgA in the animals immunised with L. lactis
      pSEC:mrpA and L. lactis pCWA:mrpA respectively. A significant reduction of renal
      bacterial colonisation was observed in both groups of mice (P<0.05) after P.
      mirabilis challenge. This is the first example of a P. mirabilis fimbrial antigen
      expressed in a food-grade live strain with promising applications in vaccine
      design.

PMID- 17540604
TI  - [Nicotine substitutes during pregnancy].

PMID- 17540605
TI  - [Is cerebral palsy preventable?].

PMID- 17540606
TI  - [Power Doppler Index for preoperative ovarian tumors discrimination].
AB  - OBJECTIVE: To assess the performance of a power doppler vascularity index in the
      preoperative diagnosis of ovarian malignancy. PATIENTS AND METHODS: Two
      successive series of adnexal masses (N=101 and N=82) were examined prospectively
      with power Doppler before surgical treatment. A vascularity index, called Power
      Doppler Index (PDI), based on the number of colored pixels, was estimated on
      selected frames (defined region of interest covering the entire tumor) of the
      tumors using an in house color-quantifying program. The first study was
      monocentric to test the inter- and intraobserver reproducibilities and the
      availability of the parameter. The second was multicentric to validate the first
      results. The sensitivity and specificity of PDI, resistance index (RI) and
      subjective visual scoring were compared using receiver operating characteristic
      (ROC) curves. RESULTS: Histology identified 23 malignant and 78 benign lesions in
      the first study and 34 malignant and 48 benign tumors in the second. PDI was
      considerably higher in malignant than in benign lesions (0.34+/-0.04 vs 0.12+/
      0.06 (P<0.001)). Intra-observer and interobserver variability of PDI was low
      (intraclass correlation coefficients estimated at 0.99 and 0.98, respectively).
      The PDI cut-off value for differential diagnosis was set at 0.265 (26.5% of the
      tumor is colored) in the first study and 0.107 in the second. Sensitivity and
      specificity were 100% (95% CI [87.8; 100.0]) and 97.4% (95% CI [91.0; 99.7]),
      respectively, for PDI in the first study compared to 75% (95% CI [72.9; 90.7])
      and 60% (95% CI [56.3; 92.5]) in the second study. Using logistic regression,
      visual Doppler scoring performed best. DISCUSSION AND CONCLUSION: The Power
      Doppler Index obtained using our color quantifying software has discriminating
      power for adnexal masses but visual Doppler scoring performs best.

PMID- 17540607
TI  - [The opinion of the French Comite technique des vaccinations and Conseil
      superieur d'hygiene publique (9th March 2007) concerning vaccination against HPV
      strains 6, 11, 16 and 18].

PMID- 17540608
TI  - Lrrk2-associated parkinsonism is a major cause of disease in Northern Spain.
AB  - Herein we describe a comparative clinical and genetic study of Lrrk2-associated
      parkinsonism in Northern Spain. In our sample from the Basque region, Lrrk2
      R1441G and G2019S account for 15 out of 50 kindreds (30%) with familial
      Parkinson's disease. We observe common founder haplotypes for both R1441G and
      G2019S carriers. Our findings highlight the importance of Lrrk2 parkinsonism in
      this population and may have important consequences for its extended Diaspora in
      North, Central and South Americas.

PMID- 17540609
TI  - Oxidative DNA damage and augmentation of poly(ADP-ribose) polymerase/nuclear
      factor-kappa B signaling in patients with type 2 diabetes and microangiopathy.
AB  - Although oxidative stress and the subsequent DNA damage is one of the obligatory
      signals for poly(ADP-ribose) polymerase (PARP) activation and nuclear factor
      kappa B (NFkappaB) alterations, these molecular aspects have not been
      collectively examined in epidemiological and clinical settings. Therefore, this
      study attempts to assess the oxidative DNA damage and its downstream effector
      signals in peripheral blood lymphocytes from Type 2 diabetes subjects without and
      with microangiopathy along with age-matched non-diabetic subjects. The basal DNA
      damage, lipid peroxidation and protein carbonyl content were significantly
      (p<0.05) higher in patients with and without microangiopathy compared to control
      subjects. Formamido Pyrimidine Glycosylase (FPG)-sensitive DNA strand breaks
      which represents reliable indicator of oxidative DNA damage were also
      significantly (p<0.001) higher in diabetic patients with (19.41+/-2.5) and
      without microangiopathy (16.53+/-2.0) compared to control subjects (1.38+/-0.85).
      Oxidative DNA damage was significantly correlated to poor glycemic control. PARP
      mRNA expression and PARP activity were significantly (p<0.05) increased in cells
      from diabetic patients with (0.31+/-0.03 densitometry units; 0.22+/
      0.02PARPunits/mgprotein, respectively) and without (0.35+/-0.02; 0.42+/-0.05)
      microangiopathy compared to control (0.19+/-0.02; 0.11+/-0.02) subjects. Diabetic
      subjects with and without microangiopathy exhibited a significantly (p<0.05)
      higher (80%) NFkappaB binding activity compared to control subjects. In diabetic
      patients, FPG-sensitive DNA strand breaks correlated positively with PARP gene
      expression, PARP activity and NFkappaB binding activity. This study provides a
      comprehensive molecular evidence for increased oxidative stress and genomic
      instability in Type 2 diabetic subjects even prior to vascular pathology and
      hence reveals a window of opportunity for early therapeutic intervention.

PMID- 17540610
TI  - Pharmacogenomics of Type I interferon therapy: a survey of response-modifying
      genes.
AB  - Interferon-beta (IFN-beta) is routinely prescribed as an immunomodulatory
      treatment for multiple sclerosis (MS), but is associated with variable clinical
      efficacy. Ideally an early predictor of response status would allow more rational
      provision of this therapy. Both pharmacogenomic and expression analysis have
      highlighted IFN-beta regulated genes which may influence treatment efficacy. In
      this review we have summarized and discussed the main genes identified by these
      studies in MS patients, and supplemented this with data from similar studies of
      Type I IFN treatment in hepatitis.

PMID- 17540611
TI  - Fellowship of the BCLA case report.

PMID- 17540612
TI  - 2,4-Dichlorophenoxyacetic acid: effects on Syrian hamster embryo (SHE) cell
      transformation, c-Myc expression, DNA damage and apoptosis.
AB  - 2,4-Dichlorophenoxyacetic acid (2,4-D) is a selective, systemic auxin-type
      herbicide extensively used throughout the world. The present research was aimed
      at studying effects of low and non-cytotoxic concentrations of 2,4-D on SHE cells
      in relation with carcinogenicity. Effects were studied on Syrian hamster
      morphological cell transformation, c-Myc expression - both at the gene and
      protein level - DNA damage and apoptosis. 2,4-D significantly induced cell
      transformation at 11.5 microM and 23 microM (i.e. 2.5 microg/mL and 5 microg/mL).
      An increase in the expression of the transcription factor c-Myc, measured by use
      of RT-PCR with respect to mRNA level and by Western blotting for protein level
      was registered at these concentrations, as well as genotoxic effects evaluated
      with the single-cell gel electrophoresis (Comet) assay. Consequences for
      apoptosis of 2,4-D treatment were also investigated. The fluorochrome acridine
      orange was used to study DNA fragmentation as a marker of apoptosis. No effect on
      apoptosis was found at 2,4-D concentrations that induced cell transformation.
      This was confirmed by the unchanged expression of Bcl-2 and Bax, two regulator
      genes of the mitochondrial pathway of apoptosis. Our results demonstrate the
      transforming and genotoxic effects of low concentrations of 2,4-D in mammalian
      cells. This information contributes to a better understanding of the mechanism of
      2,4-D toxicity in mammalian cells and demonstrates that 2,4-D should be
      considered as potentially hazardous to humans.

PMID- 17540613
TI  - The luminescence response of diamine-liganded europium complexes upon resonant
      and pre-resonant excitation.
AB  - The luminescence of four europium thenoyltrifluoroacetonate complexes containing
      diamine ligands is studied in solutions. The compounds are resonantly excited in
      the ligand absorption band by means of high-power nanosecond UV laser pulses.
      Additionally, a continuous light source is also used for resonant, as well as pre
      resonant excitation of the complexes. The luminescence response characterizes the
      synthesized europium coordination complexes as emissive compounds suitable for
      fluorometric applications. Related to the possible usefulness of the diamine
      liganded Eu complexes as luminescent labels for sensing and imaging of biological
      molecules, the luminescence response of these compounds upon UV excitation was
      probed also in aqueous media.

PMID- 17540614
TI  - Solvent effect on absorption and fluorescence spectra of coumarin laser dyes:
      evaluation of ground and excited state dipole moments.
AB  - The effect of solvents on absorption and fluorescence spectra and dipole moments
      of coumarin 307 (C307) and coumarin 522B (C522B) have been studied extensively in
      various solvents, viz., general solvents, alcohols and binary mixtures
      (acetonitrile-benzene) at 298K. The bathchromic shift observed in absorption and
      fluorescence spectra of C307 and C522B with increasing solvent polarity indicates
      that transition involved are pi-->pi*. Solvatochromic correlations were used to
      obtain the ground and excited state dipole moments. The excited state dipole
      moments are observed to be greater than their ground state counterparts in all
      the solvents studied. Further, the experimentally obtained Deltamu were compared
      with those using normalized polarity terms E(T)(N) from Reichardt equation.

PMID- 17540615
TI  - Molecular structure, IR and NMR spectra of 2,6 distyrylpyridine by density
      functional theory and ab initio Hartree-Fock calculations.
AB  - Vibrational frequencies and gauge including atomic orbital (GIAO) 13C NMR and 1H
      NMR chemical shift values of 2,6 distyrylpyridine (C21H17N) in the ground state
      have been calculated by using the Hartree-Fock (HF) and density functional method
      (B3LYP) with 6-31G(d) basis set. These methods are proposed as a tool to be
      applied in the structural characterization of 2,6 distyrylpyridine (C21H17N). The
      title compound has C2v point group, thus providing useful support in the
      interpretation of experimental IR data. In addition, obtained results were
      related to the linear correlation plot of experimental 13C NMR, 1H NMR chemical
      shifts values and IR data.

PMID- 17540616
TI  - Molecular interactions in alcohol-ethyl methacrylate mixtures.
AB  - Molecular interaction between alcohols (1-propanol, 1-butanol, s-butanol, t
      butanol, 1-pentanol, 1-heptanol, 1-octanol and 1-decanol) with ethyl methacrylate
      has been studied in n-heptane, CCl(4) and benzene at 298K using FTIR
      spectroscopic and dielectric methods. The result obtained from both the methods
      indicates only the existence of most likely 1:1 complex formation between the
      alcohol and ethyl methacrylate in these systems. The alkyl chain length of
      alcohol and the solvent used play a significant role in the strength of hydrogen
      bond (O-H:O=C) determined on the basis of spectral and dielectric parameters.

PMID- 17540617
TI  - Dynamics of 103K/N and 184M/V HIV-1 drug resistant populations: relative
      comparison in plasma virus RNA versus CD45RO+T cell proviral DNA.
AB  - BACKGROUND: Viral populations defined by 103K/N and 184M/V as linked or single
      mutations in the HIV-1 reverse transcriptase gene were investigated in plasma
      samples and compared with previous findings in the CD45RO(+)T cell compartment.
      OBJECTIVE: To develop an ARMS assay for plasma virions and to investigate the
      expression of resistance mutations (103N and 184V) and dynamic interactions
      between proviral DNA and plasma virions. STUDY DESIGN: A clinical cross-sectional
      study, including 11 patients on lamivudine efavirenz and/or nevirapine therapy.
      The viral populations were determined by an assay based on real-time PCR and
      amplification refractory mutation system (ARMS). RESULTS: The 103N and 184V
      mutations were not detected in patients with stable low viremia. Patients
      previously exposed to mono or dual therapy often carried minor viral populations
      of either one or both mutations in plasma. The viral population with linked
      mutations (103N and 184V) was detected in two patients after more than 2 years of
      non-NNRTI HAART. CONCLUSION: The ARMS assay is useful for detecting viral quasi
      species containing efavirenz and lamivudine resistant mutations in plasma virions
      and in proviral DNA. Data suggest an unequal distribution of linked-mutation
      populations in plasma and CD45RO(+)T cells. Furthermore, the linked 103N-184V
      mutation may be more fit than the single 184V mutation and this linked population
      emerges rapidly under inadequate drug pressure.

PMID- 17540618
TI  - Oxidation of chylomicron remnant-like particles inhibits their uptake by THP-1
      macrophages by apolipoprotein E-dependent processes.
AB  - The influence of the oxidative state of chylomicron remnants (CMR) on the
      mechanisms of their uptake and induction of lipid accumulation by macrophages
      derived from the human monocyte cell line, THP-1, during foam cell formation was
      investigated using chylomicron-remnant-like particles (CRLPs) at 3 different
      levels of oxidation. The oxidative state of CRLPs was varied by exposure to
      CuSO(4) (oxCRLPs) or incorporation of the antioxidant, probucol (pCRLPs) into the
      particles. oxCRLPs caused significantly less accumulation of triacylglycerol in
      the macrophages than CRLPs, and their rate of uptake was lower, while pCRLPs
      caused more lipid accumulation and were taken up faster. Uptake of all 3 types of
      particles was inhibited to a similar extent when entry via the low density
      lipoprotein (LDL) receptor related protein (80-90%), LDL receptor (-30-40%), CD36
      (-40%) and phagocytosis (-35-40%) was blocked using lactoferrin, excess LDL, anti
      CD36 and cytochalasin D, respectively, but blocking scavenger receptors-A or -B1
      using poly inosinic acid or excess HDL had no effect. These findings show that
      oxidation of CRLPs lowers their rate of uptake and induction of lipid
      accumulation in macrophages. However, oxidation does not change the main pathways
      of internalisation of CRLPs into THP-1 macrophages, which occur mainly via the
      LRP with some contribution from the LDLr, while CD36 and phagocytosis have only a
      minor role, regardless of the oxidative state of the particles. Thus, the effects
      of CMR oxidation on foam cell formation contrast sharply with those of LDL
      oxidation and this may be important in the role of dietary oxidized lipids and
      antioxidants in modulating atherosclerosis.

PMID- 17540619
TI  - Presentation of HCV antigens to naive CD8+T cells: why the where, when, what and
      how are important for virus control and infection outcome.
AB  - T cell-mediated protection against HCV depends on constantly activated effector
      CD8(+)T cells that control emergence, spread and expansion of the virus. Why
      these cells fail to contain HCV replication in 70-80% of the individuals who
      develop persistent viremia is not clear. Although many reviews have focused on
      HCV's ability to interfere with the process of antigen presentation by dendritic
      cells (DC), only few have discussed the mechanisms whereby HCV-derived antigens
      become available for presentation to naive CD8(+)T cells. The importance of these
      mechanisms has been recently brought to light by new insight into DC biology,
      antigen processing, HCV replication and the immune system's functional anatomy.
      This review explores the different immunological scenarios in which CD8(+)T cell
      responses against HCV may be initiated. It describes the critical factors
      limiting antigen sensing and capture by APC and antigen recognition by T cells,
      and discusses how these factors may favor chronicity of HCV infection. Despite
      the lack of critical detail and hard experimental proof, this review proposes a
      model whereby liver seclusion, unproductive infection of professional antigen
      presenting cells and lack of direct tissue damage hamper the launch of a virus
      specific CD8(+)T cell response. The implications for vaccine development are also
      discussed.

PMID- 17540620
TI  - Immunogenicity of singlet oxygen modified human DNA: implications for anti-DNA
      antibodies in systemic lupus erythematosus.
AB  - Reactive oxygen species (ROS)-modified DNA has been shown to be a better and more
      discriminating immunogen than native DNA (nDNA) for the production of anti-DNA
      autoantibodies in SLE (systemic lupus erythematosus). Among ROS, the role of
      hydroxyl radical (.OH) in the induction of damage and modification of nDNA has
      been extensively studied while such documentation implicating singlet oxygen
      ((1)O(2)) in inducing immunogenicity in nDNA leading to the production of anti
      double-stranded (ds) DNA autoantibodies in SLE is not yet available. This
      prospective study was undertaken to evaluate the immunogenicity of healthy human
      dsDNA modified with (1)O(2) generated by methylene blue plus radiant light.
      Female rabbits were immunized with (1)O(2)-modified human dsDNA to raise anti
      dsDNA antibodies. (1)O(2)-modified anti-dsDNA rabbit immune sera and the (1)O(2)
      modified anti-dsDNA rabbit purified immunoglobulin G (IgG) were tested against a
      variety of dsDNA antigenic substrates through direct enzyme-linked immunosorbent
      assay (ELISA). The immunogenicity of (1)O(2)-modified human dsDNA was further
      evaluated by studying its immunoreactivity with SLE patients' sera and SLE
      patients' purified anti-dsDNA IgG. As compared to healthy human sera, (1)O(2)
      modified anti-dsDNA rabbit immune sera as well as the (1)O(2)-modified anti-dsDNA
      rabbit purified IgG demonstrated a strong affinity towards (1)O(2)-modified human
      dsDNA(.)(1)O(2)-modified human dsDNA proved to be potentially more immunogenic
      against SLE patients' whole sera and SLE patients' purified IgG as compared to
      healthy human sera. Our findings suggest that (1)O(2) may also be inducing
      immunogenicity in native dsDNA resulting in the production of anti-dsDNA
      autoantibodies as seen in SLE patients.

PMID- 17540621
TI  - Genotyping of Hepatitis C virus (HCV) in infected patients from South India.
AB  - Hepatitis C virus shows substantial nucleotide sequence diversity distributed
      throughout the viral genome. In the present study genotyping for Hepatitis C
      virus (HCV) infected patients was based on RFLP analysis of 5' UTR and using type
      specific primers of NS5B regions. It was observed that 60% of the patients (30
      patients with chronic hepatitis) were infected with variants of genotype 1 and
      40% of the patients (4 chronic hepatitis patients, 12 patients with chronic renal
      failure and 4 cirrhosis) were infected with variants of type 3 of HCV. None of
      the cirrhotic patients and patients with chronic renal failure, in the present
      study, were infected with type 1 of HCV. While PCR-RFLP, typing was rapid in
      conjunction with the primers used for RT-PCR, NS5 typing was helpful in
      determining the subtype. There was good correlation between the two typing
      methods and this method can be used as a cost-effective method for studying large
      number of samples. The study shows that predominant genotypes of HCV in South
      India include type 1 and 3. Type 3 seems to be transmitted nosocomially as
      suggested by the results in patients with chronic renal failure, as these
      patients are exposed to multiple medical interventions.

PMID- 17540622
TI  - Gene-specific nucleotide excision repair is impaired in human cells expressing
      elevated levels of high mobility group A1 nonhistone proteins.
AB  - Previous work has established that stably transfected human MCF7 cells over
      expressing high mobility group A1 proteins (HMGA1) are deficient in global
      genomic repair (GGR) following exposure to either UV light or cisplatin. To
      investigate whether HMGA1 over-expression also interferes with gene-specific
      repair, we employed a rapid and convenient quantitative polymerase chain reaction
      assay for measuring repair in unique DNA sequences. Efficiency of UV-induced
      lesion removal was assessed for two genes in MCF7 cells either induced, or not,
      to over-express transgenic HMGA1 proteins: the constitutively active HPRT gene
      and the transcriptionally silent beta-globin gene. As controls, similar
      experiments were also performed in non-transgenic MCF7 cells that do not express
      detectable levels of HMGA1 and in normal human embryonic fibroblasts that
      naturally over-express HMGA1 proteins. Our results indicate that exposure of
      cells to a UV dose of 20 J/m2 produced an average of 0.21+/-0.03 and 0.19+/-0.02
      lesions/kb in the HPRT and beta-globin genes, respectively, with no significant
      difference between HMGA1 over-expressing cells and non-expressing cells. On the
      other hand, analysis of repair following UV exposure revealed that, compared to
      controls, HMGA1 over-expressing cells take considerably longer to repair photo
      lesions in both the active HPRT and the silent beta-globin loci, with non
      expressing cells repairing 50% of lesions in HPRT 3-4 h faster than HMGA1 over
      expressing cells. Interestingly, the delay in repair is even more prolonged in
      the silent beta-globin locus in HMGA1 over-expressing cells compared to control
      cells. To our knowledge, this is the first report of HMGA1 proteins inhibiting
      nucleotide excision repair (NER) within specific genes located in either
      transcriptionally active "open", or inactive "closed", chromatin domains.
      Furthermore, taken together with previous findings, these results suggest that
      HMGA1 over-expression interferes with repair processes common to both the GGR and
      transcription-coupled repair pathways.

PMID- 17540623
TI  - Liquid chromatography-tandem mass spectrometric determination of a new
      antibacterial agent (AVE6971) in human white blood cells.
AB  - An LC-MS/MS assay for the quantitative determination of a new antibacterial agent
      (AVE6971) has been developed and validated in human white blood cells (WBC). The
      assay involved a lysing procedure of white blood cells and ultra centrifugation
      of the extracts. Chromatography was performed on a Supelcosil ABZ+ C(18) (2.1 mm
      x 50 mm, 5 microm) column using a mobile phase consisting of
      methanol/acetonitrile/10mM ammonium formate mixture (10:30:60, v/v/v) at a flow
      rate of 0.2 ml/min. The linearity was within the range of 10-10000 ng/ml of
      extracts, corresponding to 0.5-500 ng of AVE6971 in WBC pellets tubes. The
      validated lower limit of quantification was 10 ng/ml. The inter- and intra-run
      coefficients of variation (CV) for the assay were <12.9% and the accuracy were
      from -9.0 to -1.2%. AVE6971 was stable in WBC for at least 1 month at -75 degrees
      C. This assay proved to be suitable for the determination of AVE6971 in WBC from
      clinical studies.

PMID- 17540624
TI  - Sugar microanalysis by HPLC with benzoylation: improvement via introduction of a
      C-8 cartridge and a high efficiency ODS column.
AB  - An HPLC protocol for sugar microanalysis based on the formation of ultraviolet
      absorbing benzoyl chloride derivatives was improved. Here, samples were prepared
      with a C-8 cartridge and analyzed with a high efficiency ODS column, in which
      porous spherical silica particles 3 microm in diameter were packed. These devices
      allowed us to simultaneously quantify multiple sugars and sugar alcohols up to 10
      ng/ml and to provide satisfactory separations of some sugars, such as fructose
      and myo-inositol and sorbitol and mannitol. This protocol, which does not require
      special apparatuses, should become a powerful tool in sugar research.

PMID- 17540625
TI  - Radical peroxidation of palmitoyl-lineloyl-glycerophosphocholine liposomes:
      Identification of long-chain oxidised products by liquid chromatography-tandem
      mass spectrometry.
AB  - Liquid chromatography coupled with electrospray tandem mass spectrometry (LC
      MS/MS) was used to identify palmitoyl-lineloyl-glycerophosphatidylcholine
      oxidation products (PL(O(1-6))PC). Structural and positional isomers of keto,
      hydroxy and/or epoxy, and hydroperoxide derivatives of PLPC were identified based
      on MS/MS data, namely product ions attributed to lyso-phosphatidylcholines,
      product ions formed by loss of nH(2)O and H(2)O(2) from [MH](+) ions groups, and
      product ions involving the hydroxy groups, providing information about the
      position of these groups and of the double bonds along the carbon chain of
      lineloyl moiety.

PMID- 17540626
TI  - Usefulness of multi-parameter opiates-amphetamines-cocainics analysis in hair of
      drug users for the evaluation of an abuse profile by means of LC-APCI-MS-MS.
AB  - The report presents a segmental hair analysis for the retrospective multi
      parameter evaluation of drugs of abuse including opioids, cocainics and
      amphetamines. The analysis was carried out with the use of liquid chromatography
      atmospheric pressure chemical ionization tandem mass spectrometry (LC-APCI-MS
      MS). The authors have evaluated the differences in the contents of particular
      opiates in the hair as related to the origin of a sample taken from Polish drug
      users taking "Polish heroin", and also from heroin abusers from Western European
      countries taking "Western heroin". The results indicate distinct differences in
      the 6-MAM concentration values in the Polish and foreigners, suggesting that the
      foreigners take products containing high concentrations of heroin and the Polish
      take the poppy product "compote" characterized by its variable and low heroin
      content. An additional argument for a different abuse profile in the Polish and
      Western drug users is found in the presence of cocaine detected in hair samples
      originating from the latter, while cocaine is much less frequently detected in
      Polish drug users.

PMID- 17540627
TI  - Surface-dependent fibrinopeptide A accessibility to thrombin.
AB  - Fibrinogen adsorption and more recently fibrin formation at interfaces has been
      reported to depend on surface properties of the underlying substrate. To provide
      insight into the surface-dependent mechanism of fibrinopeptide A (FpA) release
      and fibrin formation, the accessibility and susceptibility of FpA to thrombin
      catalyzed fibrinopeptide cleavage were examined using polyclonal anti-FpA IgG
      binding and surface plasmon resonance (SPR). The amount of accessible FpA on
      adsorbed fibrinogen was significantly influenced by surface properties of the
      underlying substrate (methyl- and carboxyl-terminated self-assembled monolayers).
      Roughly 2.7 times more FpA was available on fibrinogen adsorbed at the
      hydrophobic vs. negatively charged surface. Upon exposure of adsorbed fibrinogen
      to thrombin, 100% of the available FpA was enzymatically cleaved at both
      surfaces, indicating that the extent of FpA release and fibrin formation is a
      function of the surface-dependent FpA availability. The results presented herein
      suggest negatively charged surfaces impair FpA accessibility, and therefore lead
      to reduced FpA release and subsequent fibrin formation. As such, negatively
      charged surfaces may be useful in minimizing surface-induced thrombosis initiated
      via fibrin formation thereby aiding in the development of more biocompatible
      blood-contacting devices.

PMID- 17540628
TI  - Biomechanics and biophysics of cancer cells.
AB  - The past decade has seen substantial growth in research into how changes in the
      biomechanical and biophysical properties of cells and subcellular structures
      influence, and are influenced by, the onset and progression of human diseases.
      This paper presents an overview of the rapidly expanding, nascent field of
      research that deals with the biomechanics and biophysics of cancer cells. The
      review begins with some key observations on the biology of cancer cells and on
      the role of actin microfilaments, intermediate filaments and microtubule
      biopolymer cytoskeletal components in influencing cell mechanics, locomotion,
      differentiation and neoplastic transformation. In order to set the scene for
      mechanistic discussions of the connections among alterations to subcellular
      structures, attendant changes in cell deformability, cytoadherence, migration,
      invasion and tumor metastasis, a survey is presented of the various quantitative
      mechanical and physical assays to extract the elastic and viscoelastic
      deformability of cancer cells. Results available in the literature on cell
      mechanics for different types of cancer are then reviewed. Representative case
      studies are presented next to illustrate how chemically induced cytoskeletal
      changes, biomechanical responses and signals from the intracellular regions act
      in concert with the chemomechanical environment of the extracellular matrix and
      the molecular tumorigenic signaling pathways to effect malignant transformations.
      Results are presented to illustrate how changes to cytoskeletal architecture
      induced by cancer drugs and chemotherapy regimens can significantly influence
      cell mechanics and disease state. It is reasoned through experimental evidence
      that greater understanding of the mechanics of cancer cell deformability and its
      interactions with the extracellular physical, chemical and biological
      environments offers enormous potential for significant new developments in
      disease diagnostics, prophylactics, therapeutics and drug efficacy assays.

PMID- 17540629
TI  - A DNA microarray analysis of chemokine and receptor genes in the rat dental
      follicle--role of secreted frizzled-related protein-1 in osteoclastogenesis.
AB  - The dental follicle, a loose connective tissue sac that surrounds the unerupted
      tooth, appears to regulate the osteoclastogenesis needed for eruption; i.e., bone
      resorption to form an eruption pathway. Thus, DNA microarray studies were
      conducted to determine which chemokines and their receptors were expressed
      chronologically in the dental follicle, chemokines that might attract osteoclast
      precursors. In the rat first mandibular molar, a major burst of
      osteoclastogenesis occurs at day 3 with a minor burst at day 10. The results of
      the microarray confirmed our previous studies showing the gene expression of
      molecules such as CSF-1 and MCP-1 in the dental follicle cells. Other new genes
      also were detected, including secreted frizzled-related protein-1 (SFRP-1), which
      was found to be downregulated at days 3 and 9. Using rat bone marrow cultures to
      conduct in vitro osteoclastogenic assays, it was demonstrated that SFRP-1
      inhibited osteoclast formation in a concentration-dependent fashion. However,
      with increasing concentrations of SFRP-1, the number of TRAP-positive mononuclear
      cells increased suggesting that SFRP-1 inhibits osteoclast formation by
      inhibiting the fusion of mononuclear cells (osteoclast precursors). Co-culturing
      bone marrow mononuclear cells and dental follicle cells demonstrated that the
      dental follicle cells were secreting a product(s) that inhibited
      osteoclastogenesis, as measured by counting of TRAP-positive osteoclasts. Adding
      an antibody either to SFRP-1 or OPG partially restored osteoclastogenesis. Adding
      both anti-SFRP-1 and anti-OPG fully negated the inhibitory effect of the follicle
      cells upon osteoclastogenesis. These results strongly suggest that SFRP-1 and
      OPG, both secreted by the dental follicle cells, use different pathways to exert
      their inhibitory effect on osteoclastogenesis. Based on these in vitro studies of
      osteoclastogenesis, it is likely that the downregulation of SFRP-1 gene
      expression in the dental follicle at days 3 and 9 is a contributory factor in
      allowing the major and minor bursts of osteoclastogenesis to occur. Thus,
      inhibition of SFRP-1 gene expression in combination with inhibition of OPG gene
      expression likely are critical events in enabling alveolar bone resorption to
      occur such that teeth will erupt.

PMID- 17540631
TI  - When and how to perform allergy tests in children and adults with atopic
      dermatitis.

PMID- 17540630
TI  - Effects of long-term estrogen replacement therapy on the prevalence and area of
      periarticular tibial osteophytes in surgically postmenopausal cynomolgus monkeys.
AB  - Osteoarthritis (OA) occurs naturally in cynomolgus macaques. The purposes of the
      present study were to: 1) develop histological measurement schemes to measure the
      cross-sectional area of axial and abaxial osteophytes in the proximal tibia; 2)
      determine the effects of long-term estrogen replacement therapy (ERT) on
      osteophyte prevalence and area; and 3) assess relationships between osteophyte
      size and risk factors of OA (age and body weight) and concurrent bone and
      cartilage lesions. Adult female cynomolgus macaques (n=180) were bilaterally
      ovariectomized (OVX) and were treated for 3 years with ERT, soy phytoestrogens
      (SPE), or no hormones (OVX controls). At necropsy, the prevalence and cross
      sectional area of periarticular tibial osteophytes were evaluated histologically.
      Treatment effects on osteophyte prevalence and area were evaluated using Chi
      square analyses and Kruskal-Wallis test, respectively; other comparisons were
      evaluated using regression analyses. The prevalence of abaxial osteophytes in the
      medial tibial plateau was not significantly affected by treatment group; however,
      the prevalence of abaxial osteophytes in the lateral tibial plateau was
      significantly lower in ERT group than SPE group (p<0.01). The total number of
      abaxial osteophytes (sum of lateral and medial) was significantly lower in ERT
      group compared to OVX and SPE groups. Neither the prevalence of axial osteophytes
      nor the sum of lateral and medial axial osteophytes was significantly affected by
      treatment in either tibial plateau. There were no significant treatment effects
      on axial or abaxial osteophyte cross-sectional area in either tibial plateau.
      There was a significant positive correlation between abaxial osteophyte area and
      SCB thickness in the medial tibial plateau (p=0.048); however, there were no
      significant correlations between abaxial osteophyte area (medial or lateral) and
      age or body weight. In this model of naturally occurring OA, long-term ERT does
      not consistently reduce the prevalence, and has no significant effects on cross
      sectional area, of periarticular tibial osteophytes.

PMID- 17540632
TI  - Getting more and more complex: the pathophysiology of atopic eczema.
AB  - Atopic eczema (AE) is a multifactorial chronic inflammatory skin disease
      characterized by pruritic, typically distributed eczematous skin lesions.
      Deficiencies in innate and adaptive immunity based on a genetic predisposition
      result in skin barrier dysfunction with hyperreactivity to environmental stimuli
      and susceptibility to skin infections which influence the course and severity of
      AE. In this review, we provide an overview of the complex pathophysiology of AE
      with a focus on recent advances published in this field.

PMID- 17540633
TI  - Is there a role for topically delivered eicosapentaenoic acid in the treatment of
      psoriasis?
AB  - The n-3 fatty acids have demonstrable biological activities and have been
      associated with many health improvements from child brain development to
      arthritis. In this review we sought to pull together the works that have examined
      the potential use of n-3 fatty acids in psoriasis. The rationale of using EPA
      and/or its metabolites is supported by findings which suggest that it has anti
      inflammatory properties and plays an important role in the resolution phase of
      inflammation. EPA use in psoriasis has also been demonstrated in trials using
      oral, intravenous, and topical preparations, with generally positive outcomes.
      Depth profile analysis revealed that EPA and its metabolite, 15-HEPE are
      deposited in the epidermis, particularly in the metabolically active basal layer.
      This is considered advantageous in psoriasis therapy. Currently there are many
      unknowns about psoriasis aetiology and the effects of blocking different
      cytokines have on the disease progression. Furthermore not enough is known about
      EPA effects on cellular immunity other than via prostaglandin and leukotriene
      synthesis to fully understand the mode of action of EPA. However, evidence so far
      suggests EPA does have a potential role in the treatment of psoriasis, in
      particular for topical treatments either as an active anti-inflammatory agent by
      itself, or as a dual action permeation enhancer for other anti-psoriatic
      treatments. The challenges include optimising the delivery of EPA to the skin and
      determining the derivatives of EPA which would give maximal effects, and
      overcoming pharmacokinetic and formulation problems to optimally deliver EPA to
      its intended target cells.

PMID- 17540634
TI  - Multiple endocrine neoplasia type 2b associated with lichen nitidus.
AB  - Multiple endocrine neoplasia (MEN) type 2B syndrome is an autosomal dominantly
      inherited endocrine disorder with rare skin manifestations. We report the case of
      a 19-year-old Turkish girl who presented with skin-colored flat papules scattered
      all over the trunk and extremities. Additionally, she had marfanoid habitus,
      thick lips, and multiple flesh-colored papules over the inner eyelids and oral
      mucosa. Histopathological examination of one of the trunk lesions was consistent
      with lichen nitidus. Her past medical history was significant for medullary
      thyroid carcinoma. Genetic testing showed a point mutation in exon 16 at codon
      918 (M918T) in the RET proto-oncogene. Based on all these findings, MEN type 2B
      was diagnosed. To the best of our knowledge we report the first case of MEN type
      2B associated with lichen nitidus.

PMID- 17540635
TI  - Tissue prognostic markers for adoptive immunotherapy in melanoma.
AB  - Adoptive immunotherapy for melanoma appears to be a promising approach. The aim
      of our study was to discuss the role of "tumour tissue" immunogenicity in
      response to adoptive immunotherapy. We thus studied the potential correlation
      between the expression of some melanocyte differentiation antigens, adhesion
      molecules and cytokines expressed by the tumour cells and the survival of
      patients receiving an adoptive immunotherapy with autologous Tumour Infiltrating
      Lymphocytes (TIL). An immunohistochemical study was performed on the lymph node
      samples obtained from 38 patients who received autologous TIL plus interleukin-2.
      Frozen sections were immunostained for melanocyte differentiation antigens (Melan
      A and gp100), MHC molecules (Class I and II), adhesion molecules (ICAM-1, LFA-3)
      and suppressive cytokines (IL-10, TGF-beta and alpha-MSH). Expression levels of
      each marker were evaluated using a semi-quantitative visual scale. Using a
      multivariate analysis, a low expression level of TGF-beta by tumour cells was
      significantly associated with a prolonged relapse-free survival. A low expression
      level of TGF-beta, IL-10, ICAM-1 and alpha-MSH by tumour cells was significantly
      associated with a longer overall survival. This work suggests that a weak
      expression of immunosuppressive cytokines (IL-10, TGF-beta and alpha-MSH) could
      be a favourable prognostic marker for patients receiving autologous TIL.

PMID- 17540636
TI  - Isolation and characterization of putative epidermal stem cells derived from
      Cashmere goat fetus.
AB  - This study was undertaken to select putative epidermal stem cells from cultured
      keratinocytes in Cashmere goat fetus and to characterize them in stem cell
      nature. The keratinocytes were separated enzymatically from fetuses of 12-16
      weeks of gestation and co-cultured with mitotically inactivated fetal skin
      fibroblasts. Putative epidermal stem cells were selected by rapid adherence on
      collagen type IV substrate and maintained in three different medium conditions:
      high Ca(2+) concentration, low Ca(2+) concentration, and low Ca(2+) concentration
      with 50% conditioned medium. The results indicated that epidermal basal cells
      grew clonally on the feeder layer and were maintained for approximately 48
      population doublings without showing signs of replicative senescence. Clonal
      analysis revealed the presence of three clonal types: holoclones, meroclones and
      paraclones. Selected keratinocytes on collagen IV substrate could be propagated
      serially in three medium conditions and the population showed high colony
      formation efficiency, the same morphology with a high nuclear to cytoplasmic
      ratio and positive expression of p63, Keratin 19, Keratin 15 and CD71, which are
      believed to be possible specific markers for keratinocyte stem cells. This study
      reports a method to isolate a selected keratinocyte population with the
      characteristics of stem cells.

PMID- 17540637
TI  - Bioadhesive film for dermal and transdermal drug delivery.
AB  - This paper describes an innovative transdermal drug delivery system, a
      monolaminated bioadhesive film in which the usual constituents of transdermal
      patches (backing, drug and adhesive) have been condensed in one single layer,
      denominated Patch-non-Patch. The main characteristics of the film is that it is
      not self-adhesive in the dry state but becomes adhesive only when applied on wet
      skin. This characteristic is due to the presence of a small amount of adhesive,
      unable to make the system self-adhesive, but capable of restoring the
      adhesiveness in contact with a small amount of water. From the results obtained
      to date, it appears that the technology Patch-non-Patch has the potentiality to
      be successfully applied to the pharmaceutical and cosmetic market. On the skin
      the film is flexible, invisible and adapts to all skin irregularities. The system
      has been shown to be highly efficient, releasing a high percentage of the active
      included in most cases. Additionally, the inclusion of other excipients can
      modulate drug delivery, thus improving the versatility of the product. Finally,
      the second generation Patch-non-Patch, made occlusive on the skin surface, can
      further broaden the potential application.

PMID- 17540638
TI  - Is metronidazole 0.75% gel effective in the treatment of seborrhoeic dermatitis?
      A double-blind, placebo controlled study.
AB  - The study aimed to evaluate the effectiveness of metronidazole 0.75% gel in
      patients with mild and moderate seborrhoeic dermatitis. Sixty-seven patients with
      seborrhoeic dermatitis were enrolled. Cases were randomly treated with
      metronidazole 0.75% gel or placebo for four weeks and were additionally followed
      up for another four weeks. Patients were evaluated by scoring before the
      treatment, once a week during the treatment and twice after the cessation of the
      treatment within a 15-day interval. Furthermore, patient satisfaction and doctor
      global evaluation were done at the end of the treatment and of the study as well.
      In the metronidazole group 33 patients (median age: 26, total severity score:
      15.0 +/- 11.0 (median +/- interquartile range) and in the placebo group 34
      patients (median age: 26, total severity score: 13.0 +/- 7.5) were enrolled in
      the study. Three patients from the metronidazole group and four patients from the
      placebo group did not attend to follow-up visits. Erythema, scales, papule,
      pruritus and the total severity scores in both group decreased significantly
      during the treatment when compared with the basal levels (p < 0.05). There was no
      difference between the two groups in terms of efficacy (p > 0.05). Total severity
      scores were found as 7.33 +/- 1.08 and 6.43 +/- 0.93 in the metronidazole and
      placebo groups at the end of the treatment, respectively. After the cessation of
      the treatment, all scores had increased rapidly. Total severity scores were 10.40
      +/- 1.54 and 11.20 +/- 1.53 in the metronidazole and placebo groups one month
      after the cessation of the treatment, respectively. Both metronidazole 0.75% gel
      and the placebo were well tolerated by the patients. In conclusion, in the
      treatment of seborrhoeic dermatitis, administration of metronidazole 0.75% gel is
      well tolerated but it is only as effective as placebo and the disease severity
      quickly returns to the basal levels after the cessation of treatment.

PMID- 17540639
TI  - Perioperative management of patients on anti-platelets and anti-coagulants
      presenting for dermatological surgical procedures. A UK survey.
AB  - There are an increasing number of our patients on antiplatelet and anticoagulant
      medications. In the absence of clear guidelines for the perioperative management
      of these patients presenting for operative dermatological procedures, we
      undertook a pilot survey of the current practices of dermatologists in the United
      Kingdom. The aims of our study were to determine whether there was uniformity of
      practice and whether the modes of practice differed from those outlined in the
      literature for other related specialities, and to debate whether there is a need
      for national guidelines with this regard. A postal survey of 185 dermatologists
      was conducted. The response rate was 50%. Overall, most respondents (61%) stated
      that their practice was primarily based on personal preference and only 30%
      stated that it was based on the local Unit policy. Only 34% of the Consultants
      based their practice on evidence-based medicine. There appeared to be significant
      variations in current practice amongst dermatologists. Some aspects of practice
      were found to vary from those recommended in the literature. The findings of this
      study emphasise the importance of national guidelines for the use of anti
      platelet and anti-coagulant medications in cutaneous surgery specifically and in
      surgery in general.

PMID- 17540640
TI  - Quantification of female pattern hair loss: a study in a Turkish population.
AB  - Studies dealing with the relationship between the clinical staging of female
      pattern hair loss (FPHL) and quantitative measurements of hair parameters are
      limited. This study was performed to quantify Turkish women's hair
      characteristics in FPHL, to assess the relationship between clinical
      presentations of FPHL with hair density and anagen hair ratio and to compare the
      differences in hair parameters between FPHL and normal women, using
      epiluminescence microscopy combined with digital image analysis (Trichoscan).
      Hair density and anagen hair ratio measurements of 39 patients with FPHL were
      evaluated according to clinical stages and compared with those of 31 healthy
      volunteers. The results of digital image analysis were compared with the results
      of visual counting using the photomacrographs of the same images. Mid-scalp hair
      density and anagen ratio of the patients were detected to be significantly lower
      than those of the controls. The visual counting detected significant differences
      among the hair densities of all groups including controls, Ludwig I, and Ludwig
      II/III groups, while digital image analysis revealed a significant difference
      only between controls and Ludwig II/III groups. Thus digital image analysis was
      found to underestimate hair density, and the amount of underestimation
      demonstrated a positive correlation with hair density. In conclusion, diminished
      hair density seems to be the main sign in the clinical diagnosis of hair loss,
      although digital image analysis was found to be less competent than visual
      counting in detecting hair density. Thus, the increase in hair density in the
      assessment of various treatment modality effects may be underestimated by digital
      image analysis.

PMID- 17540641
TI  - Management of adult patients with cutaneous melanoma without distant metastasis.
      2005 update of the French Standards, Options and Recommendations guidelines.
      Summary report.

PMID- 17540642
TI  - Flushing and increase of serum tryptase after mechanical irritation of a solitary
      mastocytoma.
AB  - Solitary mastocytomas are infiltrates of mast cells in the upper corium,
      appearing at any side of the body as brownish-reddish plaques in the first months
      of life. Their course is benign with a spontaneous regression in most cases. A 5
      month-old boy presented a 5 x 3 cm sized brownish-yellow plaque on the back of
      his right hand. His parents reported repeated episodes of swelling and blistering
      of the skin lesion as well as recurrent systemic flush-reactions. General
      laboratory parameters were without pathological findings including a normal serum
      tryptase (5.5 microg/L). A few minutes after rubbing, the lesion became
      urticarially swollen and the infant developed a general flush reaction
      accompanied by a bilateral miosis and asthma-like symptoms which disappeared
      completely after oral administration of 7 drops of dimentinden. Assessment of the
      serum tryptase two hours after the provocation revealed a more than 5-fold
      increase (29.3 microg/L) compared to the basic value. We conclude that
      uncontrolled stroking of mastocytomas should be avoided in patients with a
      systemic reaction in their history, since this case demonstrates that despite its
      limited size, mechanical irritation of a solitary mastocytoma may induce strong
      systemic symptoms as witnessed by transient increase of the serum tryptase, which
      to our knowledge has not been described in the literature before.

PMID- 17540643
TI  - Pigment synthesizing (animal type) melanoma with satellite metastasis.

PMID- 17540644
TI  - Alkaptonuric ochronosis.

PMID- 17540645
TI  - Lymphoedema: a rare complication of inflammatory rheumatism. Successful treatment
      with etanercept.

PMID- 17540646
TI  - Cicatricial pemphigoid with prominent alopecia.

PMID- 17540647
TI  - Localized linear IgA disease showing contact dermatitis-like eruption.

PMID- 17540648
TI  - Occupational allergic contact dermatitis to cresyl glycidyl ether (CGE).

PMID- 17540649
TI  - Development of multiple basal cell carcinomas in mycosis fungoides treated with
      oral bexarotene.

PMID- 17540650
TI  - Two unusual cases of median raphe penile cysts.

PMID- 17540651
TI  - Mycosis fungoides showing incomplete response to topical 5-aminolaevulinic acid
      phototherapy.

PMID- 17540652
TI  - Cutaneous deep necrosis with dermatomyositis: correlation with interstitial
      pneumonia.

PMID- 17540653
TI  - Early development of disseminated nocardiosis during immunosuppressive treatment
      for pemphigus vulgaris.

PMID- 17540654
TI  - Poliosis developing in a melanocytic nevus.

PMID- 17540655
TI  - Scrofuloderma. Presentation as a thoracic tumour.

PMID- 17540656
TI  - Kissing venous malformation of the lips.

PMID- 17540657
TI  - Intractable leg ulcers associated with antiphospholipid syndrome with stasis
      dermatitis: treatment with allogeneic cultured dermal substitute.

PMID- 17540658
TI  - Lipedema and lipedematous alopecia: report of 10 new cases.

PMID- 17540659
TI  - Faint innate hypomelanotic spotting in black skin.

PMID- 17540660
TI  - Enhanced apoptosis in psoriatic plaques after treatment with propylthiouracil.

PMID- 17540661
TI  - Rhesus monkeys correctly read the goal-relevant gestures of a human agent.
AB  - When humans point, they reveal to others their underlying intent to communicate
      about some distant goal. A controversy has recently emerged based on a broad set
      of comparative and phylogenetically relevant data. In particular, whereas
      chimpanzees (Pan troglodytes) have difficulty in using human-generated
      communicative gestures and actions such as pointing and placing symbolic markers
      to find hidden rewards, domesticated dogs (Canis familiaris) and silver foxes
      (Urocyon cinereoargenteus) readily use such gestures and markers. These
      comparative data have led to the hypothesis that the capacity to infer
      communicative intent in dogs and foxes has evolved as a result of human
      domestication. Though this hypothesis has met with challenges, due in part to
      studies of non-domesticated, non-primate animals, there remains the fundamental
      question of why our closest living relatives, the chimpanzees, together with
      other non-human primates, generally fail to make inferences about a target goal
      of an agent's communicative intent. Here, we add an important wrinkle to this
      phylogenetic pattern by showing that free-ranging rhesus monkeys (Macaca mulatta)
      draw correct inferences about the goals of a human agent, using a suite of
      communicative gestures to locate previously concealed food. Though domestication
      and human enculturation may play a significant role in tuning up the capacity to
      infer intentions from communicative gestures, these factors are not necessary.

PMID- 17540662
TI  - Implantation of cardiac resynchronization therapy systems in the CARE-HF trial:
      procedural success rate and safety.
AB  - AIMS: To assess procedural characteristics and adjudicated procedure-related
      (<or=30 days) major adverse events among patients who underwent cardiac
      resynchronization therapy (CRT) implantation in the CARE-HF study. The CARE-HF
      study shows that CRT improves symptoms and reduces morbidity and mortality in New
      York Heart Association (NYHA) class III/IV chronic heart failure (CHF) patients.
      However, safe and proper implantation of pacing systems remains key to effective
      CRT delivery. METHODS AND RESULTS: Generalized linear modeling was used to
      examine the relationships between first implant success/failure and: NYHA class;
      beta-adrenergic blocker use; underlying ischemic vs. non-ischemic heart disease;
      history of coronary artery bypass graft or valve surgery; left ventricular (LV)
      end-diastolic volume<or=vs. >300 cm(3); and, influence of the participating study
      centres. Implantation was attempted in 404/409 patients assigned to CRT, and in
      65/404 patients assigned to medical therapy. Among these 469 patients, 450
      (95.9%) received a successfully implanted and activated device. Complications
      occurred within 24 h in 47 patients (10.0%), mainly lead dislodgments (n = 10,
      2.1%) and coronary sinus dissection/perforation (n = 10, 2.1%), and between 24 h
      and 30 days in 26 patients (5.5%), mainly lead dislodgment (n = 13, 2.8%). Mean
      LV lead stimulation threshold was significantly higher than at the right atrium
      or right ventricle, though remained stable, delivering effective, and reliable
      CRT. Implanting experience was the only predictor of procedural outcome.
      CONCLUSION: Transvenous CRT system implantation, using a CS lead designed for
      long-term LV pacing, was safe and reliable. As implanting centres become more
      experienced, this success rate is expected to increase further.

PMID- 17540663
TI  - Abrupt changes in fibrillatory wave characteristics at the termination of
      paroxysmal atrial fibrillation in humans.
AB  - AIMS: We investigated the process of spontaneous termination of atrial
      fibrillation (AF) to determine its time course from the surface ECG. METHODS AND
      RESULTS: We studied fibrillatory waves in Holter recordings of paroxysmal and
      sustained AF. Following QRS-T cancellation dominant frequencies (DFs) were
      computed and the relationship of DF to termination was scrutinized. For 57
      episodes of paroxysmal AF (PAF) in 24 patients, DF ranged from 4.4 to 6.5 Hz (5.2
      +/- 0.4 Hz) compared to 5.8 to 7.4 Hz (6.6 +/- 0.6 Hz) for sustained AF
      recordings. Comparison of the atrial frequency of the ultimate to the penultimate
      second demonstrated a drop in frequency in 51 of 57 episodes, P < 0.00001. No
      comparable change was seen at longer time periods. Moments of comparably low
      frequency without termination were only occasionally seen in patients with PAF
      but not in patients with sustained AF. CONCLUSION: Low frequency fibrillation was
      found to be much more likely to terminate. Frequency changes preceding
      spontaneous termination were abrupt, in contrast to the gradual frequency drop
      reported with drug-induced termination. The analysis of fibrillatory wave
      characteristics and their change over time might be used to target specific
      moments for pacing therapy in patients with AF.

PMID- 17540664
TI  - Clinical predictors of atrial fibrillation in Brugada syndrome.
AB  - AIMS: Atrial arrhythmias have been reported in patients with Brugada syndrome.
      The aim of this study was to evaluate clinical predictors of atrial fibrillation
      (AF) in Brugada syndrome. METHODS AND RESULTS: Patients diagnosed with Brugada
      ECG pattern were enrolled in the study. Type 1, 2, and 3 Brugada ECG pattern was
      found in 28, 56, and 31 patients, respectively. A total of 85 healthy age and
      gender-matched subjects were selected as a control group. Mean age, maximum P
      wave duration (P(max)), P-wave dispersion (P(disp)), and left atrial dimension
      were not significantly different between patients and controls. There were no
      differences between P(max), P(disp), and left atrial dimension of the type 1, 2,
      and 3 Brugada patients. Spontaneous paroxysmal AF was detected in 15 of 28 type 1
      Brugada patients (53%) and none of the type 2 and 3 Brugada patients. All 15
      patients with AF had at least one episode of paroxysmal AF and none of the
      patients showed persistent or chronic AF. All 15 patients who had paroxysmal AF
      had previous life threatening cardiac events. In contrast, paroxysmal AF did not
      occur in type 1 Brugada patients without previous life threatening cardiac
      events. In multiple regression analysis, only the occurrence of previous life
      threatening cardiac events was a risk factor for paroxysmal AF (P = 0.0001).
      CONCLUSION: It is concluded that the most important predictor of AF in Brugada
      syndrome is the occurrence of previous life threatening cardiac events.

PMID- 17540665
TI  - Dispersion of P wave duration and P wave vector in patients with atrial septal
      aneurysm.
AB  - AIMS: Atrial septal aneurysm (ASA) may be involved in the genesis of atrial
      arrhythmias as a consequence of disturbances in the propagation of
      depolarization, which may be easily assessed by P wave dispersion measurement.
      The aim of this study is to assess the dispersion of P wave duration and P wave
      vector in patients with ASA and to determine the effect of associated interatrial
      shunt on the magnitude of P wave dispersion. METHODS AND RESULTS: The study
      population consisted of 23 healthy volunteers and 88 patients with ASA base more
      than 15 mm and protrusion more than 7.5 mm. The size of aneurysms and atria was
      determined by echocardiography and P wave dispersion was measured on the surface
      ECG. In ASA patients, dispersion of P wave duration was significantly increased
      when compared with healthy controls (7.8 +/- 12.1 vs. 3.7 +/- 3.5 ms; P < 0.01).
      Dispersion of P wave vector was also significantly increased (8.5 +/- 10.1
      degrees vs. 4.6 +/- 3.6 degrees ; P < 0.005). In healthy volunteers, the mean
      values of both parameters were below the cutoff points. CONCLUSION: In patients
      with ASA, there was a significant dispersion of P wave duration and P wave
      vector. Variation in P wave duration was significantly correlated with the
      dispersion of P wave vector and age of these patients. Dispersion of P wave
      vector was significantly decreased in ASA patients with interatrial shunt. P wave
      dispersion in ASA patients may predispose to the development of atrial
      arrhythmias.

PMID- 17540666
TI  - Allelic estrogen receptor 1 (ESR1) gene variants predict the outcome of ovarian
      stimulation in in vitro fertilization.
AB  - The outcome of in vitro fertilization (IVF) depends substantially on the
      effectiveness of controlled ovarian hyperstimulation (COH) induced by
      administration of follicle-stimulating hormone (FSH). In COH, endogenously
      produced estrogens extend the action of FSH in stimulating folliculogenesis. We
      determined the associations between genetic variations in estrogen receptor ESR1
      and ESR2 genes and etiology of female infertility, and analysed the influence of
      these variations on COH outcome-the quantity and quality of oocytes retrieved.
      ESR1 PvuII T/C (rs2234693) and XbaI A/G (rs9340799) single-nucleotide
      polymorphisms (SNPs) and (TA)n microsatellite polymorphism, as well as ESR2 RsaI
      G/A (rs1256049) SNP and (CA)n microsatellite polymorphism were genotyped in 159
      IVF patients. The ovarian response to FSH was diminished in patients with
      endometriosis when compared to tubal factor infertility. ESR1 PvuII and XbaI as
      well as ESR2 RsaI SNPs were associated with the microsatellite length of the
      respective genes. Shorter ESR1 (TA)n was linked with a higher risk for
      unexplained infertility, whereas longer ESR1 (TA)n associated with PvuII*C allele
      were predictive of a better COH, but not clinical pregnancy outcome in an age
      independent manner. These data suggest the variations in ESR1 gene, in addition
      to the age of a woman, may predict the COH outcome in IVF.

PMID- 17540667
TI  - Single-dose aprepitant vs ondansetron for the prevention of postoperative nausea
      and vomiting: a randomized, double-blind phase III trial in patients undergoing
      open abdominal surgery.
AB  - BACKGROUND: The neurokinin(1) antagonist aprepitant is effective for prevention
      of chemotherapy-induced nausea and vomiting. We compared aprepitant with
      ondansetron for prevention of postoperative nausea and vomiting. METHODS: Nine
      hundred and twenty-two patients receiving general anaesthesia for major abdominal
      surgery were assigned to receive a single preoperative dose of oral aprepitant 40
      mg, oral aprepitant 125 mg, or i.v. ondansetron 4 mg in a randomized, double
      blind trial. Vomiting episodes, use of rescue therapy, and nausea severity
      (verbal rating scale) were documented for 48 h after surgery. Primary efficacy
      endpoints were complete response (no vomiting and no use of rescue therapy) 0-24
      h after surgery and no vomiting 0-24 h after surgery. The secondary endpoint was
      no vomiting 0-48 h after surgery. RESULTS: Aprepitant at both doses was non
      inferior to ondansetron for complete response 0-24 h after surgery (64% for
      aprepitant 40 mg, 63% for aprepitant 125 mg, and 55% for ondansetron, lower bound
      of 1-sided 95% CI > 0.65), superior to ondansetron for no vomiting 0-24 h after
      surgery (84% for aprepitant 40 mg, 86% for aprepitant 125 mg, and 71% for
      ondansetron; P < 0.001), and superior for no vomiting 0-48 h after surgery (82%
      for aprepitant, 40 mg, 85% for aprepitant, 125 mg, and 66% for ondansetron; P <
      0.001). The distribution of peak nausea scores was lower in both aprepitant
      groups vs ondansetron (P < 0.05). CONCLUSIONS: Aprepitant was non-inferior to
      ondansetron in achieving complete response for 24 h after surgery. Aprepitant was
      significantly more effective than ondansetron for preventing vomiting at 24 and
      48 h after surgery, and in reducing nausea severity in the first 48 h after
      surgery. Aprepitant was generally well tolerated.

PMID- 17540668
TI  - Acinetobacter baumannii meningitis in post-neurosurgical patients: clinical
      outcome and impact of carbapenem resistance.

PMID- 17540669
TI  - Decreased affinity of mosaic-structure recombinant penicillin-binding protein 2
      for oral cephalosporins in Neisseria gonorrhoeae.
AB  - OBJECTIVES: In Neisseria gonorrhoeae, the mosaic structure of penicillin-binding
      protein 2 (PBP 2), composed of fragments of PBP 2 from Neisseria cinerea and
      Neisseria perflava, was significantly associated with decreased susceptibility to
      cephalosporins, particularly oral cephalosporins. The aim of this study was to
      determine the affinity of mosaic PBP 2 for cephalosporins in N. gonorrhoeae.
      METHODS: Two types of non-mosaic PBP 2 from the type strain of N. gonorrhoeae
      (ATCC 19424) and a clinical strain (GU01-29), as well as the mosaic PBP 2 from a
      clinical strain (GU01-89), were expressed in insect cells, and recombinant PBP 2s
      were purified. ATCC 19424 and GU01-29 were susceptible to cephalosporins. GU01-89
      showed decreased susceptibility to cephalosporins. Bindings of fluorescent
      penicillin to PBP 2 were characterized by the Scatchard plot analysis. The
      affinity of the recombinant PBP 2s for cefdinir, cefixime and ceftriaxone was
      determined by PBP 2 competition assays with fluorescent penicillin. RESULTS: The
      K(d) value of mosaic PBP 2 for fluorescent penicillin was higher than that of non
      mosaic PBP 2s. The affinity of mosaic PBP 2 for cefdinir or cefixime was lower
      than that of the non-mosaic PBP 2s. The affinity of the mosaic PBP 2 for
      ceftriaxone was not changed, compared with that of the non-mosaic PBP 2s.
      CONCLUSIONS: Other mechanisms may be involved in clinical isolates with decreased
      susceptibility to cephalosporins, but this study suggests that the decreased
      affinity of mosaic-structure recombinant PBP 2 for oral cephalosporins may
      contribute to decreased susceptibility to these antibiotics in N. gonorrhoeae.

PMID- 17540670
TI  - Evaluation of daptomycin treatment of Staphylococcus aureus bacterial
      endocarditis: an in vitro and in vivo simulation using historical and current
      dosing strategies.
AB  - OBJECTIVES: A failure to daptomycin therapy and subsequent emergence of a
      daptomycin non-susceptible isolate occurred during the 1990 clinical
      investigation of daptomycin for the treatment of Staphylococcus aureus
      bacteraemia and endocarditis. We attempted to determine if this occurrence was
      reproducible in vitro and if it could be prevented by various daptomycin dosing
      strategies. METHODS: The daptomycin susceptible parent strain (SA-675) and the
      subsequent non-susceptible derivative (SA-684) were evaluated. In the rabbit
      endocarditis model, daptomycin 3 mg/kg every 8 h for 4 days was administered to
      simulate the study patient's pharmacokinetic exposure. Daptomycin doses of 1.5
      and 3 mg/kg every 12 h and 6 and 10 mg/kg every 24 and 48 h were simulated in the
      in vitro model with simulated endocardial vegetations (SEVs). RESULTS: Daptomycin
      significantly reduced bacterial counts of SA-675 in rabbits, but one in 10(5)
      10(6) organisms from vegetations of one animal had an 8-fold increase in MIC.
      Daptomycin 1.5 mg/kg every 12 h in the in vitro model demonstrated no activity
      against either strain; reduced susceptibility emerged in SA-675 (4-fold increase
      in MIC). Bactericidal activity was noted with 6 and 10 mg/kg dosing against SA
      675 with no resistance detected. The activity of the 6 mg/kg regimen was reduced
      against SA-684 but significantly improved activity was noted with 10 mg/kg daily.
      CONCLUSIONS: The emergence of resistance was successfully recreated at suboptimal
      dosing regimens while the current recommended regimen of 6 mg/kg/day prevented
      the emergence of non-susceptible mutants. Daptomycin 10 mg/kg/day demonstrated
      even more enhanced killing. Further investigation with daptomycin 10 mg/kg is
      warranted.

PMID- 17540671
TI  - In vitro effect of minocycline and colistin combinations on imipenem-resistant
      Acinetobacter baumannii clinical isolates.
AB  - OBJECTIVES: The study investigated the effect of colistin and minocycline when
      tested singly and in combination against Acinetobacter baumannii. METHODS:
      Thirteen unrelated imipenem-resistant A. baumannii clinical isolates were
      included in the study. MICs of colistin sulphate and minocycline were determined
      by broth macrodilution and Etest. Organisms were also tested against the two
      antibiotics singly and in combination using time-kill methods and an Etest-based
      method. RESULTS: Neither colistin nor minocycline when tested alone demonstrated
      bactericidal activity. However, the combination of colistin and minocycline
      demonstrated bactericidal activity against most of the isolates tested. At 24 h,
      the combination of antibiotics demonstrated synergy in 12 of the 13 isolates by
      time-kill methods. None of the isolates demonstrated synergy by Etest methods.
      CONCLUSIONS: The combination of colistin and minocycline was found to be
      bactericidal and synergistic against A. baumannii by time-kill methods. There was
      no agreement between time-kill and Etest methods for synergy testing.

PMID- 17540672
TI  - In vitro activities of carbapenem/sulbactam combination, colistin,
      colistin/rifampicin combination and tigecycline against carbapenem-resistant
      Acinetobacter baumannii.
AB  - OBJECTIVES: To determine the in vitro activities and interactions of imipenem,
      colistin and tigecycline with old antibacterial agents against carbapenem
      resistant Acinetobacter baumannii. METHODS: Forty-three carbapenem-resistant A.
      baumannii isolates from the intensive care unit of a university hospital were
      collected and their MICs of imipenem, colistin and tigecycline were determined.
      With eight randomly selected carbapenem-resistant isolates, an in vitro time-kill
      study was performed for the evaluation of antibacterial activity of colistin,
      tigecycline, imipenem/sulbactam and colistin/rifampicin. RESULTS: The time-kill
      study of colistin demonstrated bactericidal activity against A. baumannii at
      concentrations of 4xMIC and 8xMIC, whereas tigecycline showed bacteriostatic
      activity at all concentrations. The combination regimens of imipenem/sulbactam
      and colistin/rifampicin were synergistic and bactericidal at 1xMIC. CONCLUSIONS:
      Imipenem/sulbactam combination, colistin and tigecycline showed good in vitro
      activities against carbapenem-resistant A. baumannii isolates. Even though
      colistin is bactericidal against carbapenem-resistant A. baumannii, the
      colistin/rifampicin combination is more warranted in order to be certain.

PMID- 17540673
TI  - Efficacy of ertapenem in the treatment of early ventilator-associated pneumonia
      caused by extended-spectrum beta-lactamase-producing organisms in an intensive
      care unit.
AB  - OBJECTIVES: Ventilator-associated pneumonia (VAP) is a frequent complication of
      patients admitted to intensive care units (ICUs). Ertapenem is a newer carbapenem
      with good in vitro activity against extended-spectrum beta-lactamase (ESBL)
      producing organisms. However, there are no clinical data to support the use of
      ertapenem in VAP. Our purpose is to evaluate the usefulness and safety of
      ertapenem in the treatment of VAP caused by susceptible ESBL strains. METHODS:
      Ertapenem 1 g daily intravenously was given to adult patients with signs and
      symptoms of VAP beginning within 7 days of mechanical ventilation and caused by
      ESBL-producing Gram-negative organisms. RESULTS: From June 2005 to June 2006, we
      enrolled 20 adult patients hospitalized in an ICU and diagnosed with VAP due to
      Gram-negative ESBL strains. Causative organisms identified as ESBL producers
      susceptible to ertapenem were Klebsiella pneumoniae (alone in 10 cases and with
      methicillin-resistant Staphylococcus aureus in 4 cases), Enterobacter cloacae
      (2), Proteus mirabilis (2) and Citrobacter freundii (2). Clinical success was
      achieved in 16/20 (80%) of the clinically evaluable patients and in 15/20 (75%)
      of the microbiologically evaluable patients. The drug was well-tolerated; one
      patient presented a transient increase in liver enzymes. CONCLUSIONS: We believe
      this is one of the first reports to demonstrate that ertapenem has clinical
      utility in treating serious infections caused by ESBL-producing organisms.
      Ertapenem appears to be suitable for ESBL VAP therapy. This pilot study suggests
      subsequent controlled randomized trials in this indication.

PMID- 17540674
TI  - Characterization of the IncA/C plasmid pCC416 encoding VIM-4 and CMY-4 beta
      lactamases.
AB  - OBJECTIVES: To characterize the antibiotic resistance regions of pCC416, a VIM-4-
      and CMY-4-encoding plasmid from clinical enterobacteria, and to elucidate its
      relation with the CMY-encoding plasmids widely diffused in Salmonella. METHODS:
      The enterobacterial multiresistant plasmid pCC416 was derived from an Escherichia
      coli transconjugant and characterized. Conventional and long-range PCR assays
      were performed using primers specific for VIM-4- and CMY-4-encoding segments of
      pCC416. Amplicons were characterized by sequencing. blaVIM-4, blaCMY-4 and IntI1
      specific probes were prepared from PCR products and used for the identification
      of various pCC416 clones. VIM- and CMY-positive BamHI and Sau3AI fragments of
      pCC416 were cloned into pACYC184 and their sequences were determined by gene
      walking. RESULTS: The pCC416 plasmid contained two distinct resistant loci
      carrying beta-lactamase genes. The blaVIM-4 gene was part of an integron located
      in a complex, multidrug-resistant region of novel structure, interspersed with
      mobile elements or remnants thereof and being similar to various regions of other
      resistance plasmids. Nevertheless, a region in the 3' end of this structure
      resembled the respective region found in a CMY-2-encoding plasmid from
      Salmonella. The blaCMY-4 gene was identified within an 11.3 kb region also
      related to the CMY-2-encoding plasmids. CONCLUSIONS: pCC416 probably evolved from
      an IncA/C2, CMY-encoding plasmid through acquisition of a VIM-encoding In4-type
      integron providing an example of accretion of resistance determinants in a single
      replicon.

PMID- 17540675
TI  - Prior antibiotics and risk of antibiotic-resistant community-acquired urinary
      tract infection: a case-control study.
AB  - BACKGROUND: To assess the effect of previous antibiotic use on the risk of a
      resistant Escherichia coli urinary tract infection (UTI), we undertook a case
      control study with prospective measurement of outcomes in 10 general practices in
      the UK. METHODS: Urinary samples from all patients with symptoms suggestive of
      UTIs were sought, and those with a laboratory-proven E. coli infection were
      interviewed and their medical records examined. Case patients were those with
      ampicillin- or trimethoprim-resistant infections and control patients had
      infections that were susceptible to antibiotics, including ampicillin and
      trimethoprim. RESULTS: Risk of ampicillin-resistant E. coli infection in 903
      patients was associated with amoxicillin prescriptions of >or=7 days duration in
      the previous 1 month [odds ratio (OR)=3.91, 95% CI 1.64-9.34] and previous 2-3
      months (2.29, 1.12-4.70) before illness onset. For prescriptions <7 days
      duration, there was no statistically significant association. Higher doses of
      amoxicillin were associated with lower risk of ampicillin resistance. For
      trimethoprim-resistant E. coli infections, the OR was 8.44 (3.12-22.86) for
      prescriptions of trimethoprim of >or=7 days in the previous month and 13.91 (3.32
      58.31) for the previous 2-3 months. For trimethoprim prescriptions of <7 days,
      the OR was 4.03 (1.69-9.59) for the previous month but prescribing in earlier
      periods was not significantly associated with resistance. CONCLUSIONS: Within the
      community setting, exposure to antibiotics is a strong risk factor for a
      resistant E. coli UTI. High-dose, shorter-duration antibiotic regimens may reduce
      the pressure on the emergence of antibiotic resistance.

PMID- 17540676
TI  - Rapid decrease in the prevalence of macrolide-resistant group A streptococci due
      to the appearance of two epidemic clones in Cantabria (Spain).

PMID- 17540677
TI  - Total ancestry measure: quantifying the similarity in tree-like classification,
      with genomic applications.
AB  - MOTIVATION: Many classifications of protein function such as Gene Ontology (GO)
      are organized in directed acyclic graph (DAG) structures. In these
      classifications, the proteins are terminal leaf nodes; the categories 'above'
      them are functional annotations at various levels of specialization and the
      computation of a numerical measure of relatedness between two arbitrary proteins
      is an important proteomics problem. Moreover, analogous problems are important in
      other contexts in large-scale information organization--e.g. the Wikipedia online
      encyclopedia and the Yahoo and DMOZ web page classification schemes. RESULTS:
      Here we develop a simple probabilistic approach for computing this relatedness
      quantity, which we call the total ancestry method. Our measure is based on
      counting the number of leaf nodes that share exactly the same set of 'higher up'
      category nodes in comparison to the total number of classified pairs (i.e. the
      chance for the same total ancestry). We show such a measure is associated with a
      power-law distribution, allowing for the quick assessment of the statistical
      significance of shared functional annotations. We formally compare it with other
      quantitative functional similarity measures (such as, shortest path within a DAG,
      lowest common ancestor shared and Azuaje's information-theoretic similarity) and
      provide concrete metrics to assess differences. Finally, we provide a practical
      implementation for our total ancestry measure for GO and the MIPS functional
      catalog and give two applications of it in specific functional genomics contexts.
      AVAILABILITY: The implementations and results are available through our
      supplementary website at: http://gersteinlab.org/proj/funcsim. SUPPLEMENTARY
      INFORMATION: Supplementary data are available at Bioinformatics online.

PMID- 17540678
TI  - VISDA: an open-source caBIG analytical tool for data clustering and beyond.
AB  - SUMMARY: VISDA (Visual Statistical Data Analyzer) is a caBIG analytical tool for
      cluster modeling, visualization and discovery that has met silver-level
      compatibility under the caBIG initiative. Being statistically principled and
      visually interfaced, VISDA exploits both hierarchical statistics modeling and
      human gift for pattern recognition to allow a progressive yet interactive
      discovery of hidden clusters within high dimensional and complex biomedical
      datasets. The distinctive features of VISDA are particularly useful for users
      across the cancer research and broader research communities to analyze complex
      biological data. AVAILABILITY: http://gforge.nci.nih.gov/projects/visda/

PMID- 17540679
TI  - Statistical assessment of functional categories of genes deregulated in
      pathological conditions by using microarray data.
AB  - MOTIVATION: A major challenge in current biomedical research is the
      identification of cellular processes deregulated in a given pathology through the
      analysis of gene expression profiles. To this end, predefined lists of genes,
      coding specific functions, are compared with a list of genes ordered according to
      their values of differential expression measured by suitable univariate
      statistics. RESULTS: We propose a statistically well-founded method for measuring
      the relevance of predefined lists of genes and for assessing their statistical
      significance starting from their raw expression levels as recorded on the
      microarray. We use prediction accuracy as a measure of relevance of the list. The
      rationale is that a functional category, coded through a list of genes, is
      perturbed in a given pathology if it is possible to correctly predict the
      occurrence of the disease in new subjects on the basis of the expression levels
      of the genes belonging to the list only. The accuracy is estimated with multiple
      random validation strategy and its statistical significance is assessed against a
      couple of null hypothesis, by using two independent permutation tests. The
      utility of the proposed methodology is illustrated by analyzing the relevance of
      Gene Ontology terms belonging to biological process category in colon and
      prostate cancer, by using three different microarray data sets and by comparing
      it with current approaches. AVAILABILITY: Source code for the algorithms is
      available from author upon request. SUPPLEMENTARY INFORMATION: Colon cancer data
      set and a complete description of experimental results are available at:
      ftp://bioftp:76bioftpxxx@marx.ba.issia.cnr.it/supp-info.htm.

PMID- 17540680
TI  - Logistic regression for disease classification using microarray data: model
      selection in a large p and small n case.
AB  - MOTIVATION: Logistic regression is a standard method for building prediction
      models for a binary outcome and has been extended for disease classification with
      microarray data by many authors. A feature (gene) selection step, however, must
      be added to penalized logistic modeling due to a large number of genes and a
      small number of subjects. Model selection for this two-step approach requires new
      statistical tools because prediction error estimation ignoring the feature
      selection step can be severely downward biased. Generic methods such as cross
      validation and non-parametric bootstrap can be very ineffective due to the big
      variability in the prediction error estimate. RESULTS: We propose a parametric
      bootstrap model for more accurate estimation of the prediction error that is
      tailored to the microarray data by borrowing from the extensive research in
      identifying differentially expressed genes, especially the local false discovery
      rate. The proposed method provides guidance on the two critical issues in model
      selection: the number of genes to include in the model and the optimal shrinkage
      for the penalized logistic regression. We show that selecting more than 20 genes
      usually helps little in further reducing the prediction error. Application to
      Golub's leukemia data and our own cervical cancer data leads to highly accurate
      prediction models. AVAILABILITY: R library GeneLogit at
      http://geocities.com/jg_liao

PMID- 17540681
TI  - Tree Gibbs Sampler: identifying conserved motifs without aligning orthologous
      sequences.
AB  - SUMMARY: Tree Gibbs Sampler is a software for identifying motifs by
      simultaneously using the motif overrepresentation property and the motif
      evolutionary conservation property. It identifies motifs without depending on pre
      aligned orthologous sequences, which makes it useful for the extraction of
      regulatory elements in multiple genomes of both closely related and distant
      species. AVAILABILITY: The Tree Gibbs Sampler software is freely downloadable at
      https://compbio.iupui.edu/xiaomanli/LiSoftware/retrieve.php?ID=tgs

PMID- 17540682
TI  - Bayesian modelling of shared gene function.
AB  - MOTIVATION: Biological assays are often carried out on tissues that contain many
      cell lineages and active pathways. Microarray data produced using such material
      therefore reflect superimpositions of biological processes. Analysing such data
      for shared gene function by means of well-matched assays may help to provide a
      better focus on specific cell types and processes. The identification of genes
      that behave similarly in different biological systems also has the potential to
      reveal new insights into preserved biological mechanisms. RESULTS: In this
      article, we propose a hierarchical Bayesian model allowing integrated analysis of
      several microarray data sets for shared gene function. Each gene is associated
      with an indicator variable that selects whether binary class labels are predicted
      from expression values or by a classifier which is common to all genes. Each
      indicator selects the component models for all involved data sets simultaneously.
      A quantitative measure of shared gene function is obtained by inferring a
      probability measure over these indicators. Through experiments on synthetic data,
      we illustrate potential advantages of this Bayesian approach over a standard
      method. A shared analysis of matched microarray experiments covering (a) a cycle
      of mouse mammary gland development and (b) the process of in vitro endothelial
      cell apoptosis is proposed as a biological gold standard. Several useful sanity
      checks are introduced during data analysis, and we confirm the prior biological
      belief that shared apoptosis events occur in both systems. We conclude that a
      Bayesian analysis for shared gene function has the potential to reveal new
      biological insights, unobtainable by other means. AVAILABILITY: An online
      supplement and MatLab code are available at
      http://www.sykacek.net/research.html#mcabf

PMID- 17540683
TI  - Simple and fast alignment of metabolic pathways by exploiting local diversity.
AB  - MOTIVATION: An important tool for analyzing biological networks is the ability to
      perform homology searches, i.e. given a pattern network one would like to be able
      to search for occurrences of similar (sub)networks within a set of host networks.
      In the context of metabolic pathways, Pinter et al. [Bioinformatics, 2005]
      proposed to solve this computationally hard problem by restricting it to the case
      where both the pattern and host networks are trees. This restriction, however,
      severely limits the applicability of their algorithm. RESULTS: We propose a very
      fast and simple algorithm for the alignment of metabolic pathways that does not
      restrict the topology of the host or pattern network in any way; instead, our
      algorithm exploits a natural property of metabolic networks that we call 'local
      diversity property'. Experiments on a test bed of metabolic pathways from the
      BioCyc database indicate that our algorithm is much faster than the restricted
      algorithm of Pinter et al.-the metabolic pathways of two organisms can be aligned
      in mere seconds-and yet has a wider range of applicability and yields new
      biological insights. Our ideas can likely be extended to work for the alignment
      of various types of biological networks other than metabolic pathways.
      AVAILABILITY: Our algorithm has been implemented in C++ as a user-friendly
      metabolic pathway alignment tool called METAPAT. The tool runs under Linux or
      Windows and can be downloaded at http://theinf1.informatik.uni-jena.de/metapat/

PMID- 17540684
TI  - Trends in secondary prevention of ischaemic heart disease in the UK 1994 2005:
      use of individual and combination treatment.
AB  - BACKGROUND: Statins, antiplatelet drugs, beta-blockers and ACE inhibitors may
      produce marked benefits in secondary prevention of ischaemic heart disease (IHD),
      especially in combination. OBJECTIVE: To examine trends in treatment and factors
      associated with treatment using a population-based general practice database.
      DESIGN: Analysis of routinely collected computerised data from 201 general
      practices using iSOFT software contributing to the DIN-LINK database. SETTING AND
      PATIENTS: Subjects aged >or=35 years and registered with the practices; on
      average, 30 000 men and 21 000 women with IHD each year. MAIN OUTCOME MEASURE:
      Percentage of subjects with IHD receiving individual drugs and combined treatment
      in any given year. RESULTS: Between 1994 and 2005 use of drugs for secondary
      prevention increased markedly. By 2005, 80% of men and 70% of women were
      receiving a statin, 75% and 74% were receiving antiplatelet drugs, 55% and 48%
      were receiving beta-blockers and 57% and 51% were receiving an ACE inhibitor; 55%
      of men and 46% of women were receiving a statin, antiplatelet drug and either
      beta-blocker or ACE inhibitor, of whom just under half were receiving all four
      classes of drug. Gender differences were largely explained by more severe disease
      in men. In 2005, subjects less likely to receive combination therapy were older,
      had not had a myocardial infarction or revascularisation, and lacked
      comorbidities such as diabetes or hypertension. CONCLUSIONS: Despite high levels
      of statin and antiplatelet prescribing, opportunities exist for increasing the
      benefits of secondary prevention, especially through the wider use of combined
      treatments. Future targets could usefully include combination therapy.

PMID- 17540685
TI  - Psychological morbidity and illness appraisals of patients with cardiac and non
      cardiac chest pain attending a rapid access chest pain clinic: a longitudinal
      cohort study.
AB  - OBJECTIVES: To assess the psychological morbidity and illness beliefs in newly
      referred patients with chest pain, and to compare the psychological morbidity of
      patients with pain of cardiac origin with that of patients with pain of non
      cardiac origin. DESIGN: Longitudinal cohort study. SETTING: Rapid Access Chest
      Pain Clinic in a tertiary referral centre in Leicester, United Kingdom.
      PARTICIPANTS: 246 patients with acute, undifferentiated, chest pain followed up 1
      week and 2 months subsequent to clinic attendance. MAIN OUTCOME MEASURES: Levels
      of affective disturbance, health anxiety and illness perception. RESULTS: Levels
      of anxiety before clinic attendance exceeded community norms but did not
      differentiate the two groups. However, after clinic attendance levels of anxiety
      for those with a non-cardiac diagnosis significantly exceeded those of patients
      whose pain was of cardiac origin and remained above community norms 2 months
      hence. Non-cardiac patients viewed their condition as significantly less
      controllable and less understandable than those whose pain was cardiac in origin.
      Levels of depression for those with cardiac pain also significantly increased to
      above community norms after clinic attendance. CONCLUSIONS: Clinical levels of
      psychological morbidity are evident in the immediate and long-term aftermath of a
      visit to a Rapid Access Chest Pain Clinic, despite early access and provision of
      reassurance. More structured interventions appear necessary to deal with both
      distress and illness beliefs that may influence future healthcare use.

PMID- 17540686
TI  - Troponin-I concentration 72 h after myocardial infarction correlates with infarct
      size and presence of microvascular obstruction.
AB  - OBJECTIVES: The aim of this study was to use late gadolinium hyper-enhancement
      cardiac magnetic resonance (LGE-CMR) imaging to determine if a 72-h troponin-I
      measurement would provide a more accurate estimation of infarct size and
      microvascular obstruction (MVO) than serial creatine kinase (CK) or early
      troponin-I values. METHODS: LGE-CMR was performed 3.7+/-1.4 days after medical
      treatment for acute ST elevation or non-ST elevation myocardial infarction.
      Infarct size and MVO were measured and correlated with serum troponin-I
      concentrations, which were sampled 12 h and 72 h after admission, in addition to
      serial CK levels. RESULTS: Ninety-three patients, of whom 71 had received
      thrombolysis for ST elevation myocardial infarction, completed the CMR study.
      Peak CK, 12-h troponin-I, and 72-h troponin-I were related to infarct size by LGE
      CMR (r = 0.75, p<0.0001; r = 0.56, p = 0.0003; r = 0.62, p<0.0001 respectively).
      Serum biomarkers demonstrated higher values in the group with MVO compared with
      those without MVO (Peak CK 3085+/-1531 vs 1471+/-1135, p<0.001; 12-h troponin-I
      58.3+/-46.9 vs 33.4+/-40.0, p = 0.13; 72-h troponin-I 11.5+/-9.9 vs 5.5+/-4.6,
      p<0.005). The correlation between the extent of MVO and 12-h troponin-I was not
      significant (r = 0.16), in contrast to the other serum biomarkers (peak CK r =
      0.44, p<0.0001; 72-h troponin-I r = 0.46, p = 0.0002). CONCLUSION: A single
      measurement of 72-h troponin-I is similar to serial CK measurements in the
      estimation of both myocardial infarct size and extent of MVO, and is superior to
      12-h troponin-I measurements.

PMID- 17540687
TI  - Gender influence on the diagnostic accuracy of 64-slice multislice computed
      tomography coronary angiography for detection of obstructive coronary artery
      disease.
AB  - OBJECTIVE: To compare the diagnostic accuracy of 64-slice multislice computed
      tomography (MSCT) coronary angiography between female and male patients using
      conventional coronary angiography as the reference standard. DESIGN: Diagnostic
      accuracy study. SETTING: University hospital. PATIENTS: 103 consecutive patients
      (51 men, 52 women, mean (SD) age 60 (10) years) with known and suspected coronary
      artery disease underwent 64-slice MSCT. MAIN OUTCOME MEASURES: Diagnostic
      accuracy of 64-slice MSCT to detect obstructive (>or=50% luminal narrowing)
      stenoses in men and women. RESULTS: One male and two female patients were
      excluded from the analysis owing to non-diagnostic MSCT scans as a result of
      increased heart rate and breathing during the scan. Accordingly, on segmental
      level, 728/762 coronary segments were of sufficient quality in women (96% (95% CI
      95% to 97%)) and 704/723 segments were interpretable in men (97% (95% CI 96% to
      98%)). In the remaining 100 patients included in the further analyses, the
      sensitivity and specificity on a segmental level in women and men were 85% (95%
      CI 75% to 95%) vs 85% (95% CI 78% to 92%) and 99% (95% CI 98% to 100%) vs 99%
      (95% CI 98% to 100%), respectively. On a patient level, the sensitivity in women
      and men was 95% (95% CI 87% to 100%) vs 100%, specificity 93% (95% CI 83% to
      100%) vs 89% (95% CI 74% to 100%), positive predictive value 91% (95% CI 79% to
      100%) vs 94% (95% CI 86% to 100%), and negative predictive value 96% (95% CI 89%
      to 100%) vs 100%, respectively. CONCLUSION: The findings confirm the high
      diagnostic accuracy of 64-slice MSCT coronary angiography in both male and female
      patients.

PMID- 17540688
TI  - Arterial haemodynamics in patients after repair of tetralogy of Fallot: influence
      on left ventricular after load and aortic dilatation.
AB  - BACKGROUND: Recent histological studies of the aortic wall of patients with
      tetralogy of Fallot (TOF) have shown massive degeneration of the tunica media of
      the aorta. Such changes in arterial wall structure may significantly alter
      arterial wall mechanical properties, and thus cause abnormal arterial
      haemodynamics. OBJECTIVE: To test the hypothesis that after repair of TOF, there
      are abnormal arterial haemodynamics which are associated with aortic dilatation
      and which increased after load on the left ventricle. METHODS AND RESULTS: The
      subjects comprised 38 patients who had undergone complete repair of TOF, and 55
      control subjects. Systemic arterial haemodynamics were investigated by measuring
      aortic input impedance during cardiac catheterisation. The patients with TOF had
      significantly higher characteristic impedance (158 (43) dyne x s x cm(-5) x m(2)
      vs 105 (49) dyne x s x cm(-5) x m(2)) and pulse wave velocity (561 (139) cm/s vs
      417 (91) cm/s) and significantly lower total peripheral arterial compliance (0.93
      (0.39) ml/mm Hg/m(2) vs 1.24 (0.58) ml/mm Hg/m(2)) than the controls (for all
      three variables, p<0.01 vs controls), suggesting that central and peripheral
      arterial wall stiffness are increased after TOF repair. Additionally, patients
      with TOF had significantly higher arterial wave reflection than the controls
      (reflection coefficient: 0.21 (0.12) vs 0.16 (0.06)). These abnormalities in
      patients with TOF increased the pulsatile load on the left ventricle and
      significantly contributed to decreased cardiac output, even when right
      ventricular function was taken into account by multivariate regression analysis.
      The increase in aortic wall stiffness was closely associated with the increase in
      aortic root diameter. CONCLUSION: These results indicating abnormal arterial
      haemodynamics after TOF repair highlight the importance of regular monitoring of
      the systemic arterial bed and potentially relevant cardiovascular events in long
      term follow-up of TOF.

PMID- 17540689
TI  - Adverse prognosis associated with the metabolic syndrome in established coronary
      artery disease: data from the EUROPA trial.
AB  - OBJECTIVE: To assess the prevalence of metabolic syndrome, and its effect on
      cardiovascular morbidity and mortality in patients with established coronary
      disease and to explore the inter-relationships between metabolic syndrome,
      diabetes, obesity and cardiovascular risk. METHODS: The presence of metabolic
      syndrome was determined in 8397 patients with stable coronary disease from the
      European Trial on Reduction of Cardiac Events with Perindopril in Stable Coronary
      Artery Disease, with mean follow-up of 4.2 years. Metabolic syndrome was defined
      using a modified version of the National Cholesterol Education Programme
      criteria. RESULTS: Metabolic syndrome was present in 1964/8397 (23.4%) of the
      population and significantly predicted outcome; relative risk (RR) of
      cardiovascular mortality = 1.82 (95% CI 1.40 to 2.39); and fatal and non-fatal
      myocardial infarction RR = 1.50 (95% CI 1.24 to 1.80). The association with
      adverse outcomes remained significant after adjustment, RR of cardiovascular
      mortality after adjustment for conventional risks and diabetes = 1.39 (95% CI
      1.03 to 1.86). In comparison with normal weight subjects without diabetes or
      metabolic syndrome, normal weight dysmetabolic subjects (with either diabetes or
      metabolic syndrome) were at substantially increased risk of cardiovascular death
      (RR = 4.05 (95% CI 2.38 to 6.89)). The relative risks of cardiovascular death for
      overweight and obese patients with dysmetabolic status were nominally lower (RR =
      3.01 (95% CI 1.94 to 4.69) and RR = 2.35 (95% CI 1.50 to 3.68), respectively).
      CONCLUSIONS: Metabolic syndrome is associated with adverse cardiovascular
      outcome, independently of its associations with diabetes and obesity. A metabolic
      profile should form part of the risk assessment in all patients with coronary
      disease, not just those who are obese.

PMID- 17540690
TI  - The obstacles to maximising the impact of public access defibrillation: an
      assessment of the dispatch mechanism for out-of-hospital cardiac arrest.
AB  - OBJECTIVES: To determine the diagnostic accuracy of advanced medical priority
      dispatch system (AMPDS) software used to dispatch public access defibrillation
      first responders to out-of-hospital cardiac arrests (OHCA). DESIGN: All true OHCA
      events in North and West Belfast in 2004 were prospectively collated. This was
      achieved by a comprehensive search of all manually completed Patient Report Forms
      compiled by paramedics, together with autopsy reports, death certificates and
      medical records. The dispatch coding of all emergency calls by AMPDS software was
      also obtained for the same time period and region, and a comparison was made
      between these two datasets. SETTING: A single urban ambulance control centre in
      Northern Ireland. POPULATION: All 238 individuals with a presumed or actual OHCA
      in the North and West Belfast Health and Social Services Trust population of 138
      591 (2001 Census), as defined by the Utstein Criteria. MAIN OUTCOME MEASURES: The
      accurate dispatch of an emergency ambulance to a true OHCA. RESULTS: The
      sensitivity of the dispatch mechanism for detecting OHCA was 68.9% (115/167, 95%
      confidence interval (CI) 61.3% to 75.8%). However, the sensitivity for arrests
      with ventricular fibrillation (VF) was 44.4% (12/27) with sensitivity for
      witnessed VF of 47.1% (8/17). The positive predictive value was 63.5% (115/181,
      95% CI 56.1% to 70.6%). CONCLUSIONS: The sensitivity of this dispatch process for
      cardiac arrest is moderate and will constrain the effectiveness of Public Access
      Defibrillation (PAD) schemes which utilise it. TRIAL REGISTRATION: controlled
      trials.com ISRCTN07286796.

PMID- 17540691
TI  - In situ, chemical and macromolecular study of the composition of Arabidopsis
      thaliana seed coat mucilage.
AB  - A comprehensive analysis was carried out of the composition of seed coat mucilage
      from Arabidopsis thaliana using the Columbia-0 accession. Pectinaceous mucilage
      is released from myxospermous seeds upon imbibition, and in Arabidopsis consists
      of a water-soluble, outer layer and an adherent, inner layer. Analysis of
      monosaccharide composition in conjunction with digestion with pectolytic enzymes
      conclusively demonstrated that the principal pectic domain of both layers was
      rhamnogalacturonan I, and that in the outer layer this was unbranched. The
      macromolecular characteristics of the water-soluble mucilage indicated that the
      rhamnogalacturonan molecules in the outer layer were in a slightly expanded
      random-coil conformation. The inner, adherent layer remained attached to the
      seed, even after extraction with acid and alkali, suggesting that its integrity
      was maintained by covalent bonds. Confocal microscopy and monosaccharide
      composition analyses showed that the inner layer can be separated into two
      domains. The internal domain contained cellulose microfibrils, which could form a
      matrix with RGI and bind it to the seed. In effect, in the mum5-1 mutant where
      most of the inner and outer mucilage layers were water soluble, cellulose
      remained attached to the seed coat. Immunolabeling with anti-pectin antibodies
      indicated the presence of galactan and arabinan in the inner layer, with the
      latter only present in the non-cellulose-containing external domain. In addition,
      JIM5 and JIM7 antibodies labeled different domains of the inner layer, suggesting
      the presence of stretches of homogalacturonan with different levels of methyl
      esterification.

PMID- 17540692
TI  - Genetic linkages of the circadian clock-associated genes, TOC1, CCA1 and LHY, in
      the photoperiodic control of flowering time in Arabidopsis thaliana.
AB  - In Arabidopsis thaliana, the flowering time is regulated through the circadian
      clock that measures day-length and modulates the photoperiodic CO-FT output
      pathway in accordance with the external coincidence model. Nevertheless, the
      genetic linkages between the major clock-associated TOC1, CCA1 and LHY genes and
      the canonical CO-FT flowering pathway are less clear. By employing a set of
      mutants including an extremely early flowering toc1 cca1 lhy triple mutant, here
      we showed that CCA1 and LHY act redundantly as negative regulators of the
      photoperiodic flowering pathway. The partly redundant CCA1/LHY functions are
      largely, but not absolutely, dependent on the upstream TOC1 gene that serves as
      an activator. The results of examination with reference to the expression
      profiles of CO and FT in the mutants indicated that this clock circuitry is
      indeed linked to the CO-FT output pathway, if not exclusively. For this linkage,
      the phase control of certain flowering-associated genes, GI, CDF1 and FKF1,
      appears to be crucial. Furthermore, the genetic linkage between TOC1 and CCA1/LHY
      is compatible with the negative and positive feedback loop, which is currently
      believed to be a core of the circadian clock. The results of this study suggested
      that the circadian clock might open an exit for a photoperiodic output pathway
      during the daytime. In the context of the current clock model, these results will
      be discussed in connection with the previous finding that the same clock might
      open an exit for the early photomorphogenic output pathway during the night-time.

PMID- 17540693
TI  - Early rheumatoid arthritis.
AB  - BACKGROUND: This review outlines current knowledge of diagnosis, assessment,
      treatment and risk factors for early rheumatoid arthritis (RA). METHODS:
      Selective review of current literature was obtained by searching the terms
      'rheumatoid arthritis' and 'early'. RESULTS: Three issues dominate the current
      views on early RA. First, its recognition may be difficult. Many experts consider
      that early inflammatory arthritis should only be classified as RA after several
      months' of observation. Secondly, there is emphasis on early intensive treatment
      with conventional disease-modifying drugs or biologics, especially tumour
      necrosis factor inhibitors. Thirdly, there is a debate on the risk factors with
      evidence of genetic risks and environmental factors like smoking that may trigger
      RA. Developing citrullinated proteins followed by anti-cyclic citrullinated
      peptide antibodies, specific for RA, appears to be a crucial pathogenetic step.
      DISCUSSION: Early RA needs immediate specialist assessment and review. Early
      intensive therapy is effective but needs to be focussed on patients mostly at
      risk of severe progressive disease.

PMID- 17540694
TI  - Time trends and geographical variation in cataract surgery rates in England:
      study of surgical workload.
AB  - BACKGROUND: Phacoemulsification, day case surgery and Action on Cataracts have
      increased the national capacity for cataract surgery in England. AIMS: To examine
      time trends and geographical variation in rates of cataract surgery, and to
      determine whether there is evidence of overcapacity in current levels of surgical
      provision. METHODS: Hospital episode statistics (HES), the hospital inpatient
      enquiry (HIPE) and the Oxford record linkage study (ORLS) were analysed for
      cataract admissions between the 1960s and 2003. RESULTS: Annual rates of
      admission for cataract surgery in England rose 10-fold from 1968 to 2003: from 62
      episodes per 100,000 population in 1968, through 173 in 1989, to 637 in 2004. The
      overall increase in cataract surgery was reflected by increases in every age
      group for both men and women. Geographical analysis showed that there was wide
      variation across local authority areas in annual rates of cataract surgery, from
      172 to 548 people per 100,000 population in 1998-2003. The rate of surgery by
      local authority was positively correlated with the index of multiple deprivation
      (r(2) = 0.24). CONCLUSION: The huge increase in cataract surgery over time and
      the wide geographical variation in rates, raise the question of whether there is
      now overcapacity for cataract surgery. High levels of social deprivation are
      associated with high rates of cataract surgery; this may be due to an increased
      prevalence of cataract or differences in referral patterns.

PMID- 17540695
TI  - The nucleus tractus solitarius: an integrative centre with 'task-matching'
      capabilities.

PMID- 17540696
TI  - Variety is the spice of life: searching for the substrates of regional myocardial
      electrical properties.

PMID- 17540697
TI  - Exercise improves phosphatidylinositol-3,4,5-trisphosphate responsiveness of
      atypical protein kinase C and interacts with insulin signalling to peptide
      elongation in human skeletal muscle.
AB  - We investigated if acute endurance-type exercise interacts with insulin
      stimulated activation of atypical protein kinase C (aPKC) and insulin signalling
      to peptide chain elongation in human skeletal muscle. Four hours after acute one
      legged exercise, insulin-induced glucose uptake was approximately 80% higher (N =
      12, P < 0.05) in previously exercised muscle, measured during a euglycaemic
      hyperinsulinaemic clamp (100 microU ml(-1)). Insulin increased (P < 0.05) both
      insulin receptor substrate (IRS)-1 and IRS-2 associated phosphatidylinositol (PI)
      3 kinase activity and led to increased (P < 0.001) phosphorylation of Akt on
      Ser(473) and Thr(308) in skeletal muscle. Interestingly, in response to prior
      exercise IRS-2-associated PI-3 kinase activity was higher (P < 0.05) both at
      basal and during insulin stimulation. This coincided with correspondingly altered
      phosphorylation of the extracellular-regulated protein kinase 1/2 (ERK 1/2),
      p70S6 kinase (P70S6K), eukaryotic elongation factor 2 (eEF2) kinase and eEF2.
      aPKC was similarly activated by insulin in rested and exercised muscle, without
      detectable changes in aPKC Thr(410) phosphorylation. However, when adding
      phosphatidylinositol-3,4,5-triphosphate (PIP3), the signalling product of PI-3
      kinase, to basal muscle homogenates, aPKC was more potently activated (P = 0.01)
      in previously exercised muscle. Collectively, this study shows that endurance
      type exercise interacts with insulin signalling to peptide chain elongation.
      Although protein turnover was not evaluated, this suggests that capacity for
      protein synthesis after acute endurance-type exercise may be improved.
      Furthermore, endurance exercise increased the responsiveness of aPKC to PIP3
      providing a possible link to improved insulin-stimulated glucose uptake after
      exercise.

PMID- 17540698
TI  - Ageing and vascular adrenoceptor desensitization: too little, too late?

PMID- 17540699
TI  - Properties of single two-pore domain TREK-2 channels expressed in mammalian
      cells.
AB  - TREK-2 (K2P10.1), a member of the two-pore domain K+ (K2P) channel family,
      provides the background K+ conductance in many cell types, and is a target of
      neurotransmitters that act on receptors coupled to Gs and Gq. We report here that
      TREK-2 exhibits small (TREK-2S) and large (TREK-2L) conductance phenotypes when
      expressed in mammalian cell lines (COS-7, HEK293, HeLa) and in Xenopus oocytes.
      TREK-2S phenotype shows a noisy open state with a mean conductance of 54 pS (+40
      mV). TREK-2L phenotype shows a full open state (202 pS) with several short-lived
      sub-conductance levels. Both phenotypes were strongly activated by arachidonic
      acid, membrane stretch (-40 mmHg) and intracellular acidification (pH 6.4).
      Phosphorylation of TREK-2 produced by treatment of cells with activators of
      protein kinases A and C, and okadaic acid (a serine/threonine phosphatase
      inhibitor) decreased the current contributed by TREK-2S and TREK-2L, and caused
      partial switching of conductance levels from those of TREK-2S and TREK-2L to more
      intermediate values. Under this condition, TREK-2 exhibited six conducting levels
      and one closed level. TREK-2 mutants in which putative protein kinases A and C
      phosphorylation sites were mutated to alanines (S326A, S359A, S326A/S359A)
      displayed mostly TREK-2S and TREK-2L phenotypes. However, S326D and S359D mutants
      (as well as the double mutants) that mimic the phosphorylated state showed all
      six conducting levels and low channel activity. The S326A and S359A mutants did
      not significantly affect the intrinsic voltage dependence of TREK-2 in Mg2+-free
      solution. Phenotypes resembling TREK-2S and TREK-2L were also observed in
      cerebellar granule neurons that express TREK-2 mRNA. These results show that TREK
      2 exhibits two primary modes of gating that give rise to two channel phenotypes
      under dephosphorylated conditions, and that its phosphorylation shifts the gating
      mode to include intermediate conducting levels. This represents a novel mechanism
      by which receptor agonists modulate the function of a K+ channel to alter cell
      excitability.

PMID- 17540700
TI  - PPARdelta agonism induces a change in fuel metabolism and activation of an
      atrophy programme, but does not impair mitochondrial function in rat skeletal
      muscle.
AB  - PPARalpha agonism impairs mitochondrial function, but the effect of PPARdelta
      agonism on mitochondrial function is equivocal. Furthermore, PPARalpha and delta
      agonism increases muscle fatty acid oxidation, potentially via activation of
      FOXO1 signalling and PDK4 transcription. Since FOXO1 activation has also been
      suggested to increase transcription of MAFbx and MuRF-1, and thereby the
      activation of ubiquitin-proteasome mediated muscle proteolysis, this raises the
      possibility that muscle fuel selection and the induction of a muscle atrophy
      programme could be regulated by a single common signalling pathway. We therefore
      investigated the effect of PPARdelta (delta) agonist, GW610742, administration on
      muscle mitochondrial function, fuel regulation, and atrophy and growth related
      signalling pathways in vivo. Twenty-four male Wistar rats received vehicle or
      GW610742 (5 and 100 mg per kg body mass (bm)) orally for 6 days. Soleus muscle
      was used to determine maximal rates of ATP production (MRATP) in isolated
      mitochondria, gene and protein expression, and enzyme activities. MRATP were
      unchanged by GW610742. Muscle PDK2 and PDK4 mRNA expression increased with
      GW610742 (100 mg (kg bm)(-1)) compared to vehicle (P<0.05), and was paralleled by
      a twofold increase in PDK4 protein expression (P<0.05). The activity of beta
      hydroxyacyl-CoA dehydrogenase increased with GW610742 (P<0.05). Muscle MuRF1 and
      MAFbx mRNA expression was increased by GW610742 (100 mg (kg bm)(-1)) compared to
      vehicle (P<0.05), and was matched by increased protein expression (P<0.001),
      whilst Akt1 protein declined (P<0.05). There was no effect of GW610742 on 20S
      proteasome activity and mRNA expression, or the muscle DNA: protein ratio.
      GW610742 switched muscle fuel metabolism towards decreased carbohydrate use and
      enhanced lipid utilization, but did not induce mitochondrial dysfunction.
      Furthermore, GW610742 initiated a muscle atrophy programme, possibly via changes
      in the Akt1/FOXO/MAFbx and MuRF1 signalling pathway.

PMID- 17540701
TI  - Cardiac angiotensin II type I and type II receptors are increased in rats
      submitted to experimental hypothyroidism.
AB  - This study assessed the behaviour of angiotensin II (Ang II) receptors in an
      experimental hypothyroidism model in male Wistar rats. Animals were subjected to
      thyroidectomy and resting for 14 days. The alteration of cardiac mass was
      evaluated by total heart weight (HW), right ventricle weight (RVW), left
      ventricle weight (LVW), ratio of HW, RVW and LVW to body weight (BW) and atrial
      natriuretic factor (ANF) expression. Cardiac and plasma Ang II levels and serum
      T3 and T4 were determined. The mRNA and protein levels of Ang II receptors were
      investigated by RT-PCR and Western blotting, respectively. Functional analyses
      were performed using binding assays. T3 and T4 levels and the haemodynamic
      parameters confirmed the hypothyroid state. HW/BW, RVW/BW and LVW/BW ratios and
      the ANF expression were lower than those of control animals. No change was
      observed in cardiac or plasma Ang II levels. Both AT1/AT2 mRNA and protein levels
      were increased in the heart of hypothyroid animals due to a significant increase
      of these receptors in the RV. Experiments performed in cardiomyocytes showed a
      direct effect promoted by low thyroid hormone levels upon AT1 and AT2 receptors,
      discarding possible influence of haemodynamic parameters. Functional assays
      showed that both receptors are able to bind Ang II. Herein, we have identified,
      for the first time, a close and direct relation of elevated Ang II receptor
      levels in hypothyroidism. Whether the increase in these receptors in
      hypothyroidism is an alternative mechanism to compensate the atrophic state of
      heart or whether it may represent a potential means to the progression of heart
      failure remains unknown.

PMID- 17540702
TI  - Ca2+-stimulated adenylyl cyclase isoform AC1 is preferentially expressed in
      guinea-pig sino-atrial node cells and modulates the I(f) pacemaker current.
AB  - Ca(2+)-stimulated adenylyl cyclases (AC) are known to play important roles in
      neurons but have not previously been reported in the heart. Here we present the
      first evidence for selective expression of Ca(2+)-stimulated AC in the sino
      atrial node (SAN) but not in ventricular muscle of the guinea-pig heart. The AC1
      isoform of Ca(2+)-stimulated AC was shown to be present in SAN, both as mRNA
      using RT-PCR and as protein using immuno-blotting with a specific antibody.
      Confocal immuno-fluorescence studies detected membrane localization of AC1 in SAN
      cells, but no AC1 in ventricular muscle. Ca(2+)-stimulated AC8 may also be
      present in SAN. The functional importance of AC activity was investigated by
      monitoring activation of I(f) (gated by hyperpolarization and regulated by cAMP,
      which shifts activation to more depolarized voltages). Basal activity of AC in
      isolated SAN myocytes was demonstrated by the observations that an inhibitor of
      AC activity (MDL 12330A, 10 microm) shifted activation in the hyperpolarizing
      direction, while inhibition of phosphodiesterases (IBMX, 100 microm) shifted I(f)
      activation in the depolarizing direction. Buffering cytosolic Ca(2+) with the
      Ca(2+) chelator BAPTA (by exposure to BAPTA-AM) shifted activation of I(f) in the
      hyperpolarizing direction, and under these conditions the AC inhibitor MDL had
      little or no further effect. The actions of BAPTA were overcome by exposure to
      forskolin (10 microm), a direct stimulator of all AC isoforms, to restore cAMP
      levels. These effects are consistent with the functional importance of Ca(2+)
      stimulated AC, which is expected to be fundamental to initiation and regulation
      of the heartbeat.

PMID- 17540703
TI  - Rate, extent and concentration dependence of histamine-evoked Weibel-Palade body
      exocytosis determined from individual fusion events in human endothelial cells.
AB  - The rate, concentration dependence and extent of histamine-evoked Weibel-Palade
      body (WPB) exocytosis were investigated with time-resolved fluorescence
      microscopy in cultured human umbilical vein endothelial cells expressing WPB
      targeted chimeras of enhanced green fluorescent protein (EGFP). Exocytosis of
      single WPBs was characterized by an increase in EGFP fluorescence, morphological
      changes and release of WPB contents. The fluorescence increase was due to a rise
      of intra-WPB pH from resting levels, estimated as pH 5.45+/-0.26 (s.d., n=144),
      to pH 7.40. It coincided with uptake of extracellular Alexa-647, indicating the
      formation of a fusion pore, prior to loss of fluorescent contents. Delays between
      the increase in intracellular free calcium ion concentration evoked by histamine
      and the first fusion event were 10.0+/-4.42 s (n=9 cells) at 0.3 microM histamine
      and 1.57+/-0.21 s (n=15 cells) at 100 microM histamine, indicating the existence
      of a slow process or processes in histamine-evoked WPB exocytosis. The maximum
      rates of exocytosis were 1.20+/-0.16 WPB s(-1) (n=9) at 0.3 microM and 3.66+/
      0.45 WPB s(-1) at 100 microM histamine (n=15). These occurred 2-5 s after
      histamine addition and declined to lower rates with continued stimulation. The
      initial delays and maximal rate of exocytosis were unaffected by removal of
      external Ca2+ indicating that the initial burst of secretion is driven by Ca2+
      release from internal stores, but sustained exocytosis required external Ca2+.
      Data were compared to exocytosis evoked by a maximal concentration of the strong
      secretagogue ionomycin (1 microM), for which there was a delay between calcium
      elevation and secretion of 1.67+/-0.24 s (n=6), and a peak fusion rate of
      approximately 10 WPB s(-1).

PMID- 17540704
TI  - Dual control of cardiac Na+ Ca2+ exchange by PIP(2): analysis of the surface
      membrane fraction by extracellular cysteine PEGylation.
AB  - We describe a new assay to determine the fraction of cardiac Na(+)-Ca(2+)
      exchangers (NCX1) in the surface membrane of cells (F(surf)). An extracellular
      NCX1 disulphide bond is rapidly reduced by tris(2-carboxyethyl)phosphine
      hydrochloride (TCEP), cysteines are 'PEGylated' by alkylation with an impermeable
      conjugate of maleimide and a 5000 MW polyethylene glycol (MPEG), and F(surf) is
      quantified from Western blots as the fraction of NCX1 that migrates at a higher
      molecular weight. F(surf) remains less than 0.1 when NCX1 is expressed via
      transient transfections. Values of 0.15-0.4 are obtained for cell lines with
      stable NCX1 expression, 0.3 for neonatal myocytes and 0.6-0.8 for adult hearts.
      To validate the assay, we analysed an intervention that promotes clathrin
      independent endocytosis in fibroblasts. Using BHK cells, removal of extracellular
      potassium (K(+)) caused yellow fluorescent protein (YFP)-tagged NCX1 to
      redistribute diffusely into the cytoplasm within 30 min, F(surf) decreased by
      35%, and whole-cell exchange currents decreased by > 50%. In both HEK 293 and BHK
      cell lines, expression of human hPIP5Ibeta kinase significantly decreases
      F(surf). In BHK cells expressing M1 receptors, a muscarinic agonist (carbachol)
      causes a 40% decrease of F(surf) in normal media. This decrease is blocked by a
      high wortmannin concentration (3 mum), suggesting that type III
      phosphatidylinositol-4-kinase (PI4K) activity is required. As predicted from
      functional studies, carbachol increases F(surf) when cytoplasmic Ca(2) is
      increased by removing extracellular Na(+). Phorbol esters are without effect in
      BHK cells. In intact hearts, interventions that change contractility have no
      effect within 15 min, but we have identified two long-term changes. First, we
      analysed the diurnal dependence of F(surf) because messages for cardiac
      phosphatidylinositol-4-phosphate (PIP) 5-kinases increase during the light phase
      in entrained mice (i.e. during sleep). Cardiac phosphatidylinositol-(4,5)-bis
      phosphate (PIP(2)) levels increase during the light phase and F(surf) decreases
      in parallel. Second, we analysed effects of aortic banding because NCX1 currents
      do not mirror the increases of NCX1 message and protein that occur in this model.
      F(surf) decreases significantly within 10 days, and cardiac PIP and PIP(2) levels
      are significantly increased. In summary, multiple experimental approaches suggest
      that PIP(2) synthesis favours NCX1 internalization, that NCX1 internalization is
      probably clathrin-independent, and that significant changes of NCX1 surface
      expression occur physiologically and pathologically in intact myocardium.

PMID- 17540705
TI  - Dual control of cardiac Na+ Ca2+ exchange by PIP(2): electrophysiological
      analysis of direct and indirect mechanisms.
AB  - Cardiac Na(+)-Ca(2+) exchange (NCX1) inactivates in excised membrane patches when
      cytoplasmic Ca(2+) is removed or cytoplasmic Na(+) is increased. Exogenous
      phosphatidylinositol-4,5-bis-phosphate (PIP(2)) can ablate both inactivation
      mechanisms, while it has no effect on inward exchange current in the absence of
      cytoplasmic Na(+). To probe PIP(2) effects in intact cells, we manipulated PIP(2)
      metabolism by several means. First, we used cell lines with M1 (muscarinic)
      receptors that couple to phospholipase C's (PLCs). As expected, outward NCX1
      current (i.e. Ca(2+) influx) can be strongly inhibited when M1 agonists induce
      PIP(2) depletion. However, inward currents (i.e. Ca(2+) extrusion) without
      cytoplasmic Na(+) can be increased markedly in parallel with an increase of cell
      capacitance (i.e. membrane area). Similar effects are incurred by cytoplasmic
      perfusion of GTPgammaS or the actin cytoskeleton disruptor latrunculin, even in
      the presence of non-hydrolysable ATP (AMP-PNP). Thus, G-protein signalling may
      increase NCX1 currents by destabilizing membrane cytoskeleton-PIP(2)
      interactions. Second, to increase PIP(2) we directly perfused PIP(2) into cells.
      Outward NCX1 currents increase as expected. But over minutes currents decline
      substantially, and cell capacitance usually decreases in parallel. Third, using
      BHK cells with stable NCX1 expression, we increased PIP(2) by transient
      expression of a phosphatidylinositol-4-phosphate-5-kinase (hPIP5KIbeta) and a PI4
      kinase (PI4KIIalpha). NCX1 current densities were decreased by > 80 and 40%,
      respectively. Fourth, we generated transgenic mice with 10-fold cardiac-specific
      overexpression of PI4KIIalpha. This wortmannin-insensitive PI4KIIalpha was chosen
      because basal cardiac phosphoinositides are nearly insensitive to wortmannin, and
      surface membrane PI4-kinase activity, defined functionally in excised patches, is
      not blocked by wortmannin. Both phosphatidylinositol-4-phosphate (PIP) and PIP(2)
      were increased significantly, while NCX1 current densities were decreased by 78%
      with no loss of NCX1 expression. Most mice developed cardiac hypertrophy, and
      immunohistochemical analysis suggests that NCX1 is redistributed away from the
      outer sarcolemma. Cholera toxin uptake was increased 3-fold, suggesting that
      clathrin-independent endocytosis is enhanced. We conclude that direct effects of
      PIP(2) to activate NCX1 can be strongly modulated by opposing mechanisms in
      intact cells that probably involve membrane cytoskeleton remodelling and membrane
      trafficking.

PMID- 17540706
TI  - Expression of collagen and related growth factors in rat tendon and skeletal
      muscle in response to specific contraction types.
AB  - Acute exercise induces collagen synthesis in both tendon and muscle, indicating
      an adaptive response in the connective tissue of the muscle-tendon unit. However,
      the mechanisms of this adaptation, potentially involving collagen-inducing growth
      factors (such as transforming growth factor-beta-1 (TGF-beta-1)), as well as
      enzymes related to collagen processing, are not clear. Furthermore, possible
      differential effects of specific contraction types on collagen regulation have
      not been investigated. Female Sprague-Dawley rats were subjected to 4 days of
      concentric, eccentric or isometric training (n = 7-9 per group) of the medial
      gastrocnemius, by stimulation of the sciatic nerve. RNA was extracted from medial
      gastrocnemius and Achilles tendon tissue 24 h after the last training bout, and
      mRNA levels for collagens I and III, TGF-beta-1, connective tissue growth factor
      (CTGF), lysyl oxidase (LOX), metalloproteinases (MMP-2 and -9) and their
      inhibitors (TIMP-1 and 2) were measured by Northern blotting and/or real-time
      PCR. In tendon, expression of TGF-beta-1 and collagens I and III (but not CTGF)
      increased in response to all types of training. Similarly, enzymes/factors
      involved in collagen processing were induced in tendon, especially LOX (up to 37
      fold), which could indicate a loading-induced increase in cross-linking of tendon
      collagen. In skeletal muscle, a similar regulation of gene expression was
      observed, but in contrast to the tendon response, the effect of eccentric
      training was significantly greater than the effect of concentric training on the
      expression of several transcripts. In conclusion, the study supports an
      involvement of TGF-beta-1 in loading-induced collagen synthesis in the muscle
      tendon unit and importantly, it indicates that muscle tissue is more sensitive
      than tendon to the specific mechanical stimulus.

PMID- 17540707
TI  - Effect of silibinin on the pharmacokinetics of pyrazinamide and pyrazinoic acid
      in rats.
AB  - Pyrazinamide (PZA) is widely used in combination with other drugs in chemotherapy
      for tuberculosis. However, the dose-related liver injury is the main adverse
      effect of PZA and its metabolite [pyrazinoic acid (PA)]. Silibinin is the main
      flavonoid extracted from milk thistle (Silybum marianum), and it displays
      hepatoprotective properties. This study investigates the pharmacokinetics of PZA
      and PA and their interaction with silibinin in rats. The parallel study design
      was divided into six groups: PZA alone, PZA + long-term silibinin exposure, PZA +
      concomitant short-term silibinin exposure, PA alone, PA + long-term silibinin
      exposure, and PA + concomitant short-term silibinin exposure groups. The results
      indicate that the distribution ratio of PZA from bile to blood [area under the
      curve (AUC)(bile)/AUC(blood)] in the PZA + long-term silibinin exposure and PZA +
      concomitant short-term silibinin exposure groups was also not significantly
      different when compared with the PZA alone group. However, the bile-to-blood
      distribution ratio of PA was significantly decreased in the PA + long-term
      silibinin exposure and the PA + concomitant short-term silibinin exposure groups.
      On PZA administration, the blood, but not bile, levels of PA were markedly
      increased in the PZA + long-term silibinin exposure and PZA + concomitant short
      term silibinin exposure groups, but the bile-to-blood ratio of PA was decreased.
      These results suggest that the excretion pathway of PA may be blocked by
      silibinin through xanthine oxidase and hepatobiliary excretion.

PMID- 17540708
TI  - In vitro metabolic study of temsirolimus: preparation, isolation, and
      identification of the metabolites.
AB  - The in vitro metabolism of temsirolimus, (rapamycin-42-[2,2-bis-(hydroxymethyl)]
      propionate), an antineoplastic agent, was studied using human liver microsomes as
      well as recombinant human cytochrome P450s, namely CYP3A4, 1A2, 2A6, 2C8, 2C9,
      2C19, and 2E1. Fifteen metabolites were detected by liquid chromatography (LC)
      tandem mass spectrometry (MS/MS or MS/MS/MS). CYP3A4 was identified as the main
      enzyme responsible for the metabolism of the compound. Incubation of temsirolimus
      with recombinant CYP3A4 produced most of the metabolites detected from incubation
      with human liver microsomes, which was used for large-scale preparation of the
      metabolites. By silica gel chromatography followed by semipreparative reverse
      phase high-performance liquid chromatography, individual metabolites were
      separated and purified for structural elucidation and bioactivity studies. The
      minor metabolites (peaks 1-7) were identified as hydroxylated or desmethylated
      macrolide ring-opened temsirolimus derivatives by both positive and negative mass
      spectrometry (MS) and MS/MS spectroscopic methods. Because these compounds were
      unstable and only present in trace amounts, no further investigations were
      conducted. Six major metabolites were identified as 36-hydroxyl temsirolimus
      (M8), 35-hydroxyl temsirolimus (M9), 11-hydroxyl temsirolimus with an opened
      hemiketal ring (M10 and M11), N- oxide temsirolimus (M12), and 32-O-desmethyl
      temsirolimus (M13) using combined LC-MS, MS/MS, MS/MS/MS, and NMR techniques.
      Compared with the parent compound, these metabolites showed dramatically
      decreased activity against LNCaP cellular proliferation.

PMID- 17540709
TI  - Analysis of expressed sequence tags from the fungus Aspergillus oryzae cultured
      under different conditions.
AB  - We performed random sequencing of cDNAs from nine biologically or industrially
      important cultures of the industrially valuable fungus Aspergillus oryzae to
      obtain expressed sequence tags (ESTs). Consequently, 21 446 raw ESTs were
      accumulated and subsequently assembled to 7589 non-redundant consensus sequences
      (contigs). Among all contigs, 5491 (72.4%) were derived from only a particular
      culture. These included 4735 (62.4%) singletons, i.e. lone ESTs overlapping with
      no others. These data showed that consideration of culture grown under various
      conditions as cDNA sources enabled efficient collection of ESTs. BLAST searches
      against the public databases showed that 2953 (38.9%) of the EST contigs showed
      significant similarities to deposited sequences with known functions, 793 (10.5%)
      were similar to hypothetical proteins, and the remaining 3843 (50.6%) showed no
      significant similarity to sequences in the databases. Culture-specific contigs
      were extracted on the basis of the EST frequency normalized by the total number
      for each culture condition. In addition, contig sequences were compared with
      sequence sets in eukaryotic orthologous groups (KOGs), and classified into the
      KOG functional categories.

PMID- 17540710
TI  - Human hair follicles are an extrarenal source and a nonhematopoietic target of
      erythropoietin.
AB  - Erythropoietin primarily serves as an essential growth factor for erythrocyte
      precursor cells. However, there is increasing evidence that erythropoietin
      (EPO)/EPO receptor (EPO-R) signaling operates as a potential tissue-protective
      system outside the bone marrow. Arguing that growing hair follicles (HF) are
      among the most rapidly proliferating tissues, we have here explored whether human
      HFs are sources of EPO and targets of EPO-R-mediated signaling. Human scalp skin
      and microdissected HFs were assessed for EPO and EPO-R expression, and the
      effects of EPO on organ-cultured HFs were assessed in the presence/absence of a
      classical apoptosis-inducing chemotherapeutic agent. Here, we show that human
      scalp HFs express EPO on the mRNA and protein level in situ, up-regulate EPO
      transcription under hypoxic conditions, and express transcripts for EPO-R and the
      EPO-stimulatory transcriptional cofactor hypoxia-inducible factor-1alpha.
      Although EPO does not significantly alter human hair growth in vitro, it
      significantly down-regulates chemotherapy-induced intrafollicular apoptosis and
      changes the gene expression program of the HFs. The current study points to
      intriguing targets of EPO beyond the erythropoietic system: human HFs are an
      extrarenal site of EPO production and an extrahematopoietic site of EPO-R
      expression. They may recruit EPO/EPO-R signaling e.g., for modulating HF
      apoptosis under conditions of hypoxia and chemotherapy-induced stress.

PMID- 17540714
TI  - The freedom to innovate: a privilege or a right?

PMID- 17540715
TI  - FLOWERING LOCUS T protein may act as the long-distance florigenic signal in the
      cucurbits.
AB  - Cucurbita moschata, a cucurbit species responsive to inductive short-day (SD)
      photoperiods, and Zucchini yellow mosaic virus (ZYMV) were used to test whether
      long-distance movement of FLOWERING LOCUS T (FT) mRNA or FT is required for
      floral induction. Ectopic expression of FT by ZYMV was highly effective in
      mediating floral induction of long-day (LD)-treated plants. Moreover, the
      infection zone of ZYMV was far removed from floral meristems, suggesting that FT
      transcripts do not function as the florigenic signal in this system.
      Heterografting demonstrated efficient transmission of a florigenic signal from
      flowering Cucurbita maxima stocks to LD-grown C. moschata scions. Real-time RT
      PCR performed on phloem sap collected from C. maxima stocks detected no FT
      transcripts, whereas mass spectrometry of phloem sap proteins revealed the
      presence of Cm-FTL1 and Cm-FTL2. Importantly, studies on LD- and SD-treated C.
      moschata plants established that Cmo-FTL1 and Cmo-FTL2 are regulated by
      photoperiod at the level of movement into the phloem and not by transcription.
      Finally, mass spectrometry of florally induced heterografted C. moschata scions
      revealed that C. maxima FT, but not FT mRNA, crossed the graft union in the
      phloem translocation stream. Collectively, these studies are consistent with FT
      functioning as a component of the florigenic signaling system in the cucurbits.

PMID- 17540716
TI  - The Arabidopsis ATNRT2.7 nitrate transporter controls nitrate content in seeds.
AB  - In higher plants, nitrate is taken up by root cells where Arabidopsis thaliana
      NITRATE TRANSPORTER2.1 (ATNRT2.1) chiefly acts as the high-affinity nitrate
      uptake system. Nitrate taken up by the roots can then be translocated from the
      root to the leaves and the seeds. In this work, the function of the ATNRT2.7
      gene, one of the seven members of the NRT2 family in Arabidopsis, was
      investigated. High expression of the gene was detected in reproductive organs and
      peaked in dry seeds. beta-Glucuronidase or green fluorescent protein reporter
      gene expression driven by the ATNRT2.7 promoter confirmed this organ specificity.
      We assessed the capacity of ATNRT2.7 to transport nitrate in Xenopus laevis
      oocytes or when it is expressed ectopically in mutant plants deficient in nitrate
      transport. We measured the impact of an ATNRT2.7 mutation and found no difference
      from the wild type during vegetative development. By contrast, seed nitrate
      content was affected by overexpression of ATNRT2.7 or a mutation in the gene.
      Finally, we showed that this nitrate transporter protein was localized to the
      vacuolar membrane. Our results demonstrate that ATNRT2.7 plays a specific role in
      nitrate accumulation in the seed.

PMID- 17540717
TI  - Localization of the mouse 5-hydroxytryptamine(1A) receptor in lipid microdomains
      depends on its palmitoylation and is involved in receptor-mediated signaling.
AB  - In the present study, we have used wild-type and palmitoylation-deficient mouse 5
      hydroxytryptamine(1A) receptor (5-HT1A) receptors fused to the yellow fluorescent
      protein- and the cyan fluorescent protein (CFP)-tagged alpha(i3) subunit of
      heterotrimeric G-protein to study spatiotemporal distribution of the 5-HT1A
      mediated signaling in living cells. We also addressed the question on the
      molecular mechanisms by which receptor palmitoylation may regulate communication
      between receptors and G(i)-proteins. Our data demonstrate that activation of the
      5-HT1A receptor caused a partial release of Galpha(i) protein into the cytoplasm
      and that this translocation is accompanied by a significant increase of the
      intracellular Ca(2+) concentration. In contrast, acylation-deficient 5-HT1A
      mutants failed to reproduce both Galpha(i3)-CFP relocation and changes in
      [Ca(2+)](i) upon agonist stimulation. By using gradient centrifugation and
      copatching assays, we also demonstrate that a significant fraction of the 5-HT1A
      receptor resides in membrane rafts, whereas the yield of the palmitoylation
      deficient receptor in these membrane microdomains is reduced considerably. Our
      results suggest that receptor palmitoylation serves as a targeting signal
      responsible for the retention of the 5-HT1A receptor in membrane rafts. More
      importantly, the raft localization of the 5-HT1A receptor seems to be involved in
      receptor-mediated signaling.

PMID- 17540718
TI  - The ovine sexually dimorphic nucleus of the medial preoptic area is organized
      prenatally by testosterone.
AB  - A sexually dimorphic nucleus that can be identified in adult sheep by its
      characteristic pattern of cytochrome P450 aromatase mRNA exists in the
      preoptic/anterior hypothalamic area and is called the ovine sexually dimorphic
      nucleus (oSDN). In other species, male-typical sexually dimorphic preoptic nuclei
      develop under the influence of gonadal testosterone exposure. Thus, we
      hypothesized that the oSDN develops before birth in the sheep and is organized by
      exposure to testosterone. To test this, we determined whether an identifiable
      oSDN is present in the fetal lamb brain at d 130-140 gestation (term
      approximately 150 d). In situ hybridization for aromatase mRNA revealed a cell
      group in the caudal preoptic area that corresponded to the oSDN in adults.
      Quantitative analysis showed that the mean volume of the oSDN in late-gestation
      fetuses was significantly larger in male than in female lamb fetuses. We next
      treated a group of pregnant ewes with testosterone propionate (TP) from d 30-90
      gestation and measured oSDN volumes in TP-exposed and control fetuses on d 135
      gestation. The mean volume of the oSDN in female fetuses exposed to TP was
      significantly larger than in control females and also larger than in control and
      TP-exposed males. Taken together, these data demonstrate that testosterone acts
      during a prenatal critical period to organize the development of aromatase
      expressing neurons into the male-typical oSDN in sheep.

PMID- 17540719
TI  - A splicing variant of the androgen receptor detected in a metastatic prostate
      cancer exhibits exclusively cytoplasmic actions.
AB  - The androgen receptor (AR) is a ligand-activated transcription factor that
      displays genomic actions characterized by binding to androgen-response elements
      in the promoter of target genes as well as nongenomic actions that do not require
      nuclear translocation and DNA binding. In this study, we report exclusive
      cytoplasmic actions of a splicing variant of the AR detected in a metastatic
      prostate cancer. This AR variant, named AR23, results from an aberrant splicing
      of intron 2, wherein the last 69 nucleotides of the intronic sequence are
      retained, leading to the insertion of 23 amino acids between the two zinc fingers
      in the DNA-binding domain. We show that the nuclear entry of AR23 upon
      dihydrotestosterone (DHT) stimulation is impaired. Alternatively, DHT-activated
      AR23 forms cytoplasmic and perinuclear aggregates that partially colocalize with
      the endoplasmic reticulum and are devoid of genomic actions. However, in LNCaP
      cells, this cytoplasmic DHT-activated AR23 remains partially active as evidenced
      by the activation of transcription from androgen-responsive promoters, the
      stimulation of NF-kappaB transcriptional activity and by the decrease of AP-1
      transcriptional activity. Our data reveal novel cytoplasmic actions for this
      splicing AR variant, suggesting a contribution in prostate cancer progression.

PMID- 17540720
TI  - Evidence that ghrelin is as potent as growth hormone (GH)-releasing hormone
      (GHRH) in releasing GH from primary pituitary cell cultures of a nonhuman primate
      (Papio anubis), acting through intracellular signaling pathways distinct from
      GHRH.
AB  - Ghrelin is more effective than GHRH in stimulating GH release in normal adult
      humans and monkeys in vivo. This robust effect of ghrelin has been largely
      attributed to regulation of hypothalamic input, whereas the direct effect of
      ghrelin on pituitary GH release has been minimized by the observation that
      ghrelin has only a modest impact on GH release, compared with GHRH, in cultures
      prepared from human fetal pituitaries and GH-producing adenomas, as well as
      pituitaries from nonprimate species. However, comparable in vitro studies have
      not been performed to test the direct effect of ghrelin on normal adult primates.
      Therefore, in the present study, primary pituitary cell cultures from female
      baboons (Papio anubis) were used as a model system to test the direct effects of
      ghrelin on primate somatotrope function. In this model, both ghrelin and GHRH
      increased GH release in a dose-dependent fashion. Surprisingly, at maximal
      concentrations (10 nM), both ghrelin and GHRH elicited a robust increase in GH
      release (4 and 24 h, respectively), and both up-regulated GH secretagogue
      receptor and GHRH-receptor mRNA levels (24 h). Combined treatment with ghrelin
      and GHRH resulted in an additive effect on GH release, suggesting that distinct
      intracellular signaling pathways are activated by each ligand, as confirmed by
      the use of specific inhibitors of intracellular signaling. Together, these
      results present the first evidence that a direct effect of ghrelin on somatotrope
      function may play a major role in stimulating GH release in primates.

PMID- 17540721
TI  - Mice overexpressing the mitochondrial phospholipid hydroperoxide glutathione
      peroxidase in male germ cells show abnormal spermatogenesis and reduced
      fertility.
AB  - To investigate the physiological effects of mitochondrial phospholipid
      hydroperoxide glutathione peroxidase (mPHGPx) overexpression during early male
      germ cell differentiation, we have generated transgenic mice bearing the rat
      mPhgpx coding sequence driven by the mouse synaptonemal complex protein 1
      promoter, allowing the transgene to be specifically activated in the testis from
      the zygotene to diplotene stages of the first meiotic division. Northern/Western
      blotting and immunocytochemical analyses of endogenous mPHGPx expression during
      spermatogenesis showed a low enzyme level in middle-late pachytene spermatocytes,
      but not in earlier meiotic stages, and a significant increase in mPHGPx content
      in round spermatids. The histological and terminal deoxynucleotidyl transferase
      mediated dUTP nick-end labeling analysis of transgenic testes revealed a number
      of spermatogenetic defects, including primary spermatocyte apoptosis, haploid
      cell loss, and seminiferous epithelium disorganization. In line with these
      features, adult transgenic male mice also displayed a reduction in fertility.
      Results obtained in this study suggest that mPHGPx expression is tightly
      regulated in pachytene spermatocytes, with any spatial-temporal increase in
      mPHGPx expression resulting in damage to spermatogenesis and eventual loss of
      haploid cells. Present findings in the mouse may be of interest to human male
      fertility.

PMID- 17540722
TI  - Hyperglycemia enhances adipogenic induction of lipid accumulation: involvement of
      extracellular signal-regulated protein kinase 1/2, phosphoinositide 3-kinase/Akt,
      and peroxisome proliferator-activated receptor gamma signaling.
AB  - The molecular events of hyperglycemia-triggered increase in adipogenic induction
      of lipid accumulation remain unclear. We examined the effects of hyperglycemia on
      adipogenic induction of lipid accumulation and its involved signaling molecules,
      such as phosphoinositide 3-kinase (PI3K), ERKs, and peroxisome proliferator
      activated receptor gamma (PPAR gamma). Bone marrow-derived mesenchymal stem cells
      (MSCs) isolated from FVB/N mice were capable of differentiating into adipocytes
      in adipogenic medium. The effects of high glucose (HG) (25.5 mm) were assessed in
      vitro by RT-PCR, ELISA, flow cytometry, immunostaining, and immunoblotting. The
      in vivo effect of hyperglycemia was further studied in streptozotocin (STZ)
      induced diabetic FVB/N mice. Exposure of MSCs to HG enhanced adipogenic induction
      of lipid accumulation as compared with 5.5 mm glucose. HG increased PPAR gamma
      expression and PI3K activity and its downstream effector Akt phosphorylation
      during adipogenesis. Inhibition of PI3K/Akt activity with PI3K inhibitor LY294002
      or by expressing the dominant negative p85 or Akt prevented the HG-enhanced PPAR
      gamma-dependent adipogenic induction of lipid accumulation. Moreover, HG
      increased the phosphorylation of ERK1/2 during adipogenesis. MAPK/ERK inhibitor
      PD98059 inhibited the PI3K activity, Akt phosphorylation, and lipid accumulation
      triggered by HG. PI3K inhibitor LY294002 did not affect the HG-increased ERK1/2
      phosphorylation during adipogenesis. We next observed that adipogenic induction
      of lipid accumulation of MSCs isolated from STZ-induced diabetic mice is
      enhanced. Moreover, triglyceride, PPAR gamma expression, phosphorylated Akt and
      ERK1/2, and marrow fat in bones of STZ-diabetic mice were also increased. These
      results suggest that hyperglycemia enhances the adipogenic induction of lipid
      accumulation through an ERK1/2-activated PI3K/Akt-regulated PPAR gamma pathway.

PMID- 17540723
TI  - Cox-2 promotes chromogranin A expression and bioactivity: evidence for a
      prostaglandin E2-dependent mechanism and the involvement of a proximal cyclic
      adenosine 5'-monophosphate-responsive element.
AB  - The prostanoid biosynthetic enzyme cyclooxygenase-2 (Cox-2) is up-regulated in
      several neuroendocrine tumors. The aim of the current study was to employ a
      neuroendocrine cell (PC12) model of Cox-2 overexpression to identify gene
      products that might be implicated in the oncogenic and/or inflammatory actions of
      this enzyme in the setting of neuroendocrine neoplasia. Expression array and real
      time PCR analysis demonstrated that levels of the neuroendocrine marker
      chromogranin A (CGA) were 2- and 3.2-fold higher, respectively, in Cox-2
      overexpressing cells (PCXII) vs. their control (PCMT) counterparts.
      Immunocytochemical and immunoblotting analyses confirmed that both intracellular
      and secreted levels of CGA were elevated in response to Cox-2 induction.
      Moreover, exogenous addition of prostaglandin E(2) (1 microm) mimicked this
      effect in PCMT cells, whereas treatment of PCXII cells with the Cox-2 selective
      inhibitor NS-398 (100 nm) reduced CGA expression levels, thereby confirming the
      biospecificity of this finding. Levels of neuron-specific enolase were similar in
      the two cell lines, suggesting that the effect of Cox-2 on CGA expression was
      specific and not due to a global enhancement of neuroendocrine marker
      expression/differentiation. Cox-2-dependent CGA up-regulation was associated with
      significantly increased chromaffin granule number and intracellular and secreted
      levels of dopamine. CGA promoter-driven reporter gene expression studies provided
      evidence that prostaglandin E(2)-dependent up-regulation required a proximal cAMP
      responsive element (-71 to -64 bp). This study is the first to demonstrate that
      Cox-2 up-regulates both CGA expression and bioactivity in a neuroendocrine cell
      line and has major implications for the role of this polypeptide in the
      pathogenesis of neuroendocrine cancers in which Cox-2 is up-regulated.

PMID- 17540724
TI  - Glial cell line-derived neurotrophic factor: an intraovarian factor that enhances
      oocyte developmental competence in vitro.
AB  - The success of early embryonic development depends on oocyte nuclear and
      cytoplasmic maturation. We have investigated whether glial cell line-derived
      neurotrophic factor (GDNF) affects the in vitro maturation (IVM) of porcine
      oocytes and their subsequent ability to sustain preimplantation embryo
      development. GDNF and both its coreceptors, GDNF family receptor alpha-1 (GFR
      alpha-1) and the rearranged during transformation (RET) receptor, were expressed
      in oocytes and their surrounding cumulus cells derived from small and large
      follicles. When included in IVM medium, GDNF significantly enhanced cumulus cell
      expansion of both small and large cumulus-oocyte complexes and increased the
      percentage of small follicle-derived oocytes maturing to the metaphase II stage,
      although nuclear maturation of large oocytes was not significantly affected.
      Examination of cyclin B1 protein expression as a measure of cytoplasmic
      maturation revealed that in the presence of GDNF, cyclin B1 levels were
      significantly increased in large follicle-derived oocytes, as well as in oocytes
      from small follicles to a level comparable to the untreated large group. After
      activation, a significantly higher percentage of both small and large oocytes
      that were matured in the presence of GDNF developed to the blastocyst stage
      compared with untreated controls. Indeed, GDNF enhanced the blastocyst rate of
      small oocytes to levels comparable to those obtained for large oocytes matured
      without GDNF. The effect of GDNF was specific; this was evident because its
      enhancement of nuclear maturation and embryo developmental potential was blocked
      by an antibody against GFR alpha-1. Our study provides the first functional
      evidence that GDNF affects oocyte maturation and preimplantation embryo
      developmental competence in a follicular stage-dependent manner. This finding may
      provide insights for improving the formulation of IVM culture systems, especially
      for oocytes from small follicles.

PMID- 17540725
TI  - Involvement of glyceraldehyde-3-phosphate dehydrogenase in tumor necrosis factor
      related apoptosis-inducing ligand-mediated death of thyroid cancer cells.
AB  - TNF-related apoptosis-inducing ligand (TRAIL) is cytotoxic to most thyroid cancer
      cell lines, including those originating from anaplastic carcinomas, implying
      TRAIL as a promising therapeutic agent against thyroid cancers. However, signal
      transduction in TRAIL-mediated apoptosis is not clearly understood. In addition
      to its well-known glycolytic functions, glyceraldehyde-3-phosphate dehydrogenase
      (GAPDH) is a multifunctional protein, including its surprising role as a mediator
      for cell death. In this study we explored the involvement of GAPDH in TRAIL
      mediated thyroid cancer cell death. In follicular undifferentiated thyroid cells,
      S-nitrosylation and nuclear translocation of GAPDH appear to mediate TRAIL
      induced cell death at least partially, as evidenced by pretreatment with N-nitro
      L-arginine methyl ester, a competitive nitric oxide synthase inhibitor that
      partially but significantly attenuated TRAIL-induced apoptosis through the
      reduction of S-nitrosylation and nuclear translocation of GAPDH. In addition,
      GAPDH small interfering RNA partially prevented the apoptotic effect of TRAIL,
      although TRAIL-induced nitric oxide synthase stimulation and production of nitric
      oxide were not attenuated. Furthermore, nuclear localization of GAPDH was
      observed in another thyroid cancer cell line, KTC2, which is also sensitive to
      TRAIL, but not in those TRAIL insensitive cell lines: ARO, KTC1, and KTC3. These
      data indicate that nitric oxide-mediated S-nitrosylation of GAPDH and subsequent
      nuclear translocation of GAPDH might function as a mediator of TRAIL-induced cell
      death in thyroid cancer cells.

PMID- 17540726
TI  - Temporal dynamics of type 2 deiodinase expression after melatonin injections in
      Syrian hamsters.
AB  - In many species living in temperate zones, reproduction is controlled by the
      photoperiod. Recent findings have clarified that type 2 iodothyronine deiodinase
      (Dio2) plays a significant role in the photoperiodic response of gonads in the
      mediobasal hypothalamus, converting the prohormone T(4) into bioactive T(3). In
      mammals, Dio2 expression is suppressed by long-term melatonin injections,
      although the signal transduction pathways that link the melatonin signal to Dio2
      expression are unknown. As a first step to approach the problem, we have here
      investigated the temporal dynamics of the melatonin effect on Dio2 expression
      using male Syrian hamsters. Dio2 mRNA levels were found to show diurnal rhythms
      under long-day conditions in an area adjacent to the tuberoinfundibular sulcus
      and in the ependymal cell layer lining the ventrobasal walls of the third
      ventricle. Daily sc melatonin injections given in the late afternoon under long
      day condition suppressed the Dio2 mRNA levels already at the first day after the
      onset of the treatment in the ependymal cell layer lining the ventrobasal walls
      of the third ventricle, and 1 d later in an area adjacent to the
      tuberoinfundibular sulcus. These suppressive effects were sustained for at least
      2 d after a single injection. Furthermore, we examined the temporal changes of
      the Dio2 expression after the onset of the treatment, showing that the
      suppression did not occur until midday of the next day. These data suggest that
      melatonin is involved in the signal transduction mechanisms controlling the
      photoperiodic response of gonads by acting on Dio2 expression rather rapidly
      through indirect pathways.

PMID- 17540727
TI  - Rising follicle-stimulating hormone levels with age accelerate female
      reproductive failure.
AB  - Rising serum FSH levels is one of the earliest signs of human female reproductive
      aging. Whether or not elevated FSH remains a passive reflection of a diminishing
      ovarian follicle pool or actively contributes to declining female fertility with
      age has not been established. We therefore investigated female reproduction in
      mice expressing progressively rising serum levels of transgenic human FSH (Tg
      FSH, 2.5-10 IU/liter) independently of follicle depletion. We show that serum LH
      and estradiol levels and uterine size remained normal in Tg-FSH females, whereas
      ovarian weight and corpora lutea number were significantly increased up to 1.3-
      and 5-fold, respectively. Furthermore, the monotrophic FSH rise produced a
      striking biphasic effect on female fertility. Tg-FSH females less than 22 wk old
      delivered increased litter sizes, then beyond 23 wk, litter sizes decreased
      rapidly culminating in premature infertility despite continued ovary follicle
      development, and increased ovulation and uterine embryo implantation sites as
      well as normal serum levels of anti-Mullerian hormone, a marker of ovarian
      follicle reserve. We found that rising circulating Tg-FSH produced premature
      infertility by increasing embryo-fetal resorption and parturition failure with
      age. Thus, our Tg-FSH mice present a novel paradigm to investigate selective
      contributions of elevated FSH to age-related female infertility, which revealed
      that rising FSH levels, despite no exhaustion of ovarian reserve, actively
      accelerates female reproductive aging primarily by postimplantation reduction of
      embryo-fetal survival.

PMID- 17540728
TI  - Kinetics and thermodynamics of amyloid formation from direct measurements of
      fluctuations in fibril mass.
AB  - Aggregation of proteins and peptides is a widespread and much-studied problem,
      with serious implications in contexts ranging from biotechnology to human
      disease. An understanding of the proliferation of such aggregates under specific
      conditions requires a quantitative knowledge of the kinetics and thermodynamics
      of their formation; measurements that to date have remained elusive. Here, we
      show that precise determination of the growth rates of ordered protein aggregates
      such as amyloid fibrils can be achieved through real-time monitoring, using a
      quartz crystal oscillator, of the changes in the numbers of molecules in the
      fibrils from variations in their masses. We show further that this approach
      allows the effect of other molecular species on fibril growth to be characterized
      quantitatively. This method is widely applicable, and we illustrate its power by
      exploring the free-energy landscape associated with the conversion of the protein
      insulin to its amyloid form and elucidate the role of a chemical chaperone and a
      small heat shock protein in inhibiting the aggregation reaction.

PMID- 17540729
TI  - Extensively cross-reactive anti-HIV-1 neutralizing antibodies induced by gp140
      immunization.
AB  - An immunization regimen was evaluated in rabbits consisting of the soluble,
      oligomeric form of envelope glycoprotein of HIV-1, strain R2 (gp140(R2)), or the
      surface component of the same envelope (Env), gp120(R2), in the adjuvant AS02A.
      The gp140(R2) was selected based on its unusual CD4-independent phenotype and the
      exceptionally broad neutralizing response in the infected donor. The gp140(R2)
      immunogen induced antibodies that achieved 50% neutralization of 48/48, and 80%
      neutralization of 43/46 primary strains of diverse HIV-1 subtypes tested. The
      strains tested included members of standard panels of subtype B and C strains,
      and other diverse strains known to be neutralization resistant. The gp120(R2)
      induced antibodies that neutralized 9/48 of the same strains. Neutralization was
      IgG-mediated and HIV-1-specific. These results demonstrate that induction of
      truly broad spectrum neutralizing antibodies is an achievable goal in HIV-1
      vaccine development.

PMID- 17540730
TI  - The selection of acceptable protein mutations.
AB  - We have determined the general constraints that govern sequence divergence in
      proteins that retain entirely, or very largely, the same structure and function.
      To do this we collected data from three different groups of orthologous
      sequences: those found in humans and mice, in humans and chickens, and in
      Escherichia coli and Salmonella enterica. In total, these organisms have 21,738
      suitable pairs of orthologs, and these contain nearly 2 million mutations. The
      three groups differ greatly in the taxa from which they come and/or in the time
      that separates them from their last common ancestor. Nevertheless, the results we
      obtain from the three different groups are strikingly similar. For each group,
      the orthologous sequence pairs were assigned to six different divergence
      categories on the basis of their sequence identities. For categories with the
      same divergence, common accepted mutations have similar frequencies and rank
      orders in the three groups. With divergence, the width of the range of common
      mutations grows in the same manner in each group. We examined the distribution of
      mutations in protein structures. With increasing divergence, mutations increase
      at different rates in the buried, intermediate, and exposed regions of protein
      structures in a manner that explains the exponential relationship between the
      divergence of structure and sequence. This work implies that commonly allowed
      mutations are selected by a set of general constraints that are well defined and
      whose nature varies with divergence.

PMID- 17540731
TI  - EXECUTER1- and EXECUTER2-dependent transfer of stress-related signals from the
      plastid to the nucleus of Arabidopsis thaliana.
AB  - Shortly after the release of singlet oxygen ((1)O2), drastic changes in nuclear
      gene expression occur in the conditional flu mutant of Arabidopsis that reveal a
      rapid transfer of signals from the plastid to the nucleus. In contrast to
      retrograde control of nuclear gene expression by plastid signals described
      earlier, the primary effect of (1)O2 generation in the flu mutant is not the
      control of chloroplast biogenesis but the activation of a broad range of
      signaling pathways known to be involved in biotic and abiotic stress responses.
      This activity of a plastid-derived signal suggests a new function of the
      chloroplast, namely that of a sensor of environmental changes that activates a
      broad range of stress responses. Inactivation of the plastid protein EXECUTER1
      attenuates the extent of (1)O2-induced up-regulation of nuclear gene expression,
      but it does not fully eliminate these changes. A second related nuclear-encoded
      protein, dubbed EXECUTER2, has been identified that is also implicated with the
      signaling of (1)O2-dependent nuclear gene expression changes. Like EXECUTER1,
      EXECUTER2 is confined to the plastid. Inactivation of both EXECUTER proteins in
      the ex1/ex2/flu triple mutant is sufficient to suppress the up-regulation of
      almost all (1)O2-responsive genes. Retrograde control of (1)O2-responsive genes
      requires the concerted action of both EXECUTER proteins within the plastid
      compartment.

PMID- 17540733
TI  - Differential regulation of CD11b on gammadelta T cells and monocytes in response
      to unripe apple polyphenols.
AB  - Leukocyte adhesion and migration are mediated partially by CD11b/CD18 (membrane
      activated complex-1, CR3). Earlier studies have demonstrated a role for green tea
      polyphenols in down-regulating CD11b on CD8(+) T cells and monocytes. We have
      shown recently a stimulatory effect of unripe apple polyphenols (APP) on
      gammadelta T cells. Thus, we compared the effect of APP on bovine gammadelta T
      cell and monocyte CD11b expression. Purified bovine monocytes and monocyte
      depleted PBLs were cultured with APP. CD11b levels decreased on monocytes in
      response to APP. In contrast, a gammadelta T cell subset responded to APP by up
      regulating CD11b. The CD11b regulation was not seen on gammadelta T cells or
      monocytes treated with APP fractions depleted of tannins. The APP-induced down
      regulation of CD11b on monocytes was inhibited by an anti-CD11b mAb, consistent
      with previous studies showing that polyphenols bind CD11b. As expected, the anti
      CD11b mAb had no effect on the APP response in resting gammadelta T cells, as
      these cells lacked CD11b. Consistent with the changes in surface CD11b
      expression, APP-treated gammadelta T cells showed increased adherence to plastic,
      whereas monocyte adhesion was reduced. APP also induced cytokine gene expression
      in gammadelta T cells. Some polyphenols are thought of as anti-inflammatory
      agents; however, these data, as well as other ongoing studies, indicate they have
      a proinflammatory effect on gammadelta T cells. In vivo, plant polyphenols may
      enhance gammadelta T cell migration and function at sites of inflammation, where
      they could induce rapid, immune-regulatory and innate-like immune responses.

PMID- 17540734
TI  - Toll-like receptor 4 (TLR4)-dependent proinflammatory and immunomodulatory
      properties of the glycoinositolphospholipid (GIPL) from Trypanosoma cruzi.
AB  - We have demonstrated recently that the glycoinositolphospholipid (GIPL) molecule
      from the protozoan Trypanosoma cruzi is a TLR4 agonist with proinflammatory
      effects. Here, we show that GIPL-induced neutrophil recruitment into the
      peritoneal cavity is mediated by at least two pathways: one, where IL-1beta acts
      downstream of TNF-alpha, and a second, which is IL-1beta- and TNFRI-independent.
      Moreover, NKT cells participate in this proinflammatory cascade, as in GIPL
      treated CD1d(-/-) mice, TNF-alpha and MIP-2 levels are reduced significantly. As
      a consequence of this inflammatory response, spleen and lymph nodes of GIPL
      treated mice have an increase in the percentage of T and B cells expressing the
      CD69 activation marker. Cell-transfer experiments demonstrate that T and B cell
      activation by GIPL is an indirect effect, which relies on the expression of TLR4
      by other cell types. Moreover, although signaling through TNFRI contributes to
      the activation of B and gammadelta+ T cells, it is not required for increasing
      CD69 expression on alphabeta+ T lymphocytes. It is interesting that T cells are
      also functionally affected by GIPL treatment, as spleen cells from GIPL-injected
      mice show enhanced production of IL-4 following in vitro stimulation by anti-CD3.
      Together, these results contribute to the understanding of the inflammatory
      properties of the GIPL molecule, pointing to its potential role as a parasite
      derived modulator of the immune response during T. cruzi infection.

PMID- 17540735
TI  - Preferential chemotaxis of activated human CD4+ T cells by extracellular
      cyclophilin A.
AB  - The recruitment and trafficking of leukocytes are essential aspects of the
      inflammatory process. Although chemokines are thought to be the main regulators
      of cell trafficking, extracellular cyclophilins have been shown recently to have
      potent chemoattracting properties for human leukocytes. Cyclophilins are secreted
      by a variety of cell types and are detected at high levels in tissues with
      ongoing inflammation. CD147 has been identified as the main signaling receptor
      for cyclophilin A (CypA) on human leukocytes. It is interesting that the
      expression of CD147 is elevated on leukocytes from inflamed tissue, suggesting a
      correlation among the presence of extracellular cyclophilins, CD147 expression,
      and inflammatory responses. Thus, cyclophilin-CD147 interactions may contribute
      directly to the recruitment of leukocytes into inflamed tissues. In the current
      studies, we show that activated human T lymphocytes express elevated levels of
      CD147, compared with resting T cells and that these activated T cells migrate
      more readily to CypA than resting cells. Furthermore, we show that unlike resting
      CD4+ T cells, the cyclophilin-mediated migration of activated T cells does not
      require interaction with heparan sulfate receptors but instead, is dependent on
      CD147 interaction alone. Such findings suggest that cyclophilin-CD147
      interactions will be most potent when leukocytes are in an activated state, for
      example, during inflammatory responses. Thus, targeting cyclophilin-CD147
      interactions may provide a novel approach for alleviating tissue inflammation.

PMID- 17540736
TI  - The value of routine screening of staff for MRSA.

PMID- 17540737
TI  - Orthopaedic metals and their potential toxicity in the arthroplasty patient: A
      review of current knowledge and future strategies.
AB  - The long-term effects of metal-on-metal arthroplasty are currently under scrutiny
      because of the potential biological effects of metal wear debris. This review
      summarises data describing the release, dissemination, uptake, biological
      activity, and potential toxicity of metal wear debris released from alloys
      currently used in modern orthopaedics. The introduction of risk assessment for
      the evaluation of metal alloys and their use in arthroplasty patients is
      discussed and this should include potential harmful effects on immunity,
      reproduction, the kidney, developmental toxicity, the nervous system and
      carcinogenesis.

PMID- 17540738
TI  - Bone allografts: What they can offer and what they cannot.
AB  - Bone allografts can be used in any kind of surgery involving bone from minor
      defects to major bone loss after tumour resection. This review describes the
      various types of bone grafts and the current knowledge on bone allografts, from
      procurement and preparation to implantation. The surgical conditions for
      optimising the incorporation of bone are outlined, and surgeon expectations from
      a bone allograft discussed.

PMID- 17540739
TI  - Irrigation of the wounds in open fractures.
AB  - Modern principles for the treatment of open fractures include stabilisation of
      the bone and management of the soft tissues. Wound debridement and irrigation is
      thought to be the mainstay in reducing the incidence of infection. Although
      numerous studies on animals and humans have focused on the type of irrigation
      performed, little is known of the factors which influence irrigation. This paper
      evaluates the evidence, particularly with regard to additives and the mode of
      delivery of irrigation fluid. Normal saline should be used and although many
      antiseptics and antibiotics have been employed, no consensus has been reached as
      to the ideal additive. Despite the advocates of high-pressure methods
      highlighting the improved dilutional ability of such techniques, the results are
      inconclusive and these irrigation systems are not without complications. New
      systems for debridement are currently being investigated, and an ideal method has
      yet to be determined.

PMID- 17540740
TI  - Metal ion levels after metal-on-metal Ring total hip replacement: a 30-year
      follow-up study.
AB  - Metal-on-metal bearings for total hip replacement (THR) are becoming increasingly
      popular. Improved wear characteristics mean that these articulations are being
      inserted into younger patients in the form of THR and resurfacing procedures.
      This has led to concerns regarding potential carcinogenicity because of the
      increased exposure to metal ions that the procedure brings. We have studied the
      serum cobalt and chromium concentrations in patients who had primary, well-fixed
      Ring metal-on-metal THRs for more than 30 years. The levels of cobalt and
      chromium were elevated by five and three times, respectively compared with those
      in our reference groups. Metal-on-metal articulations appear to be the source of
      metal ions throughout the life of the prosthesis. In three patients who had
      undergone revision of a previous metal-on-metal THR to a metal-on-polyethylene
      replacement the levels of metal ions were within the normal range. The elevations
      of cobalt and chromium ions seen in our study were comparable with those in
      patients with modern metal-on-metal THRs.

PMID- 17540741
TI  - Isolated acetabular liner exchange compared with complete acetabular component
      revision in revision of primary uncemented acetabular components: a study of 1649
      revisions from the Norwegian Arthroplasty Register.
AB  - We analysed the results of different strategies in the revision of primary
      uncemented acetabular components reported to the Norwegian Arthroplasty Register.
      The aim was to compare the risk of further acetabular revision after isolated
      liner exchange and complete component revision. The results of exchanging well
      fixed components were also compared with those of exchanging loose acetabular
      components. The period studied was between September 1987 and April 2005. The
      following groups were compared: group 1, exchange of liner only in 318 hips;
      group 2, exchange of well-fixed components in 398; and group 3, exchange of loose
      components in 933. We found that the risk of a further cup revision was lower
      after revision of well-fixed components (relative risk from a Cox model (RR) =
      0.56, 95% confidence interval 0.37% to 0.87%) and loose components (RR = 0.56,
      95% confidence interval 0.39% to 0.80%), compared with exchange of the liner in
      isolation. The most frequent reason for a further acetabular revision was
      dislocation, accounting for 61 (28%) of the re-revisions. Other reasons for
      further revision included pain in 27 (12%), loosening in 24 (11%) and infection
      in 20 (9%). Re-revisions because of pain were less frequent when complete
      component (fixed or loose) revision was undertaken compared with isolated
      exchange of the liner (RR = 0.20 (95% confidence interval 0.06% to 0.65%) and RR
      = 0.10 (95% confidence interval 0.03% to 0.30%), respectively). The risk of
      further acetabular revision for infection, however, did not differ between the
      groups. In this study, exchange of the liner only had a higher risk of further
      cup revision than revision of the complete acetabular component. Our results
      suggest that the threshold for revising well-fixed components in the case of
      liner wear and osteolysis should be lowered.

PMID- 17540742
TI  - Treatment of failed arthroscopic acetabular labral debridement by femoral chondro
      osteoplasty: a case series of five patients.
AB  - Femoroacetabular impingement is recognised as being a cause of labral tears and
      chondral damage. We report a series of five patients who presented with
      persistent pain in the hip after arthroscopy for isolated labral debridement. All
      five had a bony abnormality consistent with cam-type femoroacetabular
      impingement. They had a further operation to correct the abnormality by chondro
      osteoplasty of the femoral head-neck junction. At a mean follow-up of 16.3 months
      (12 to 24) all had symptomatic improvement.

PMID- 17540743
TI  - Increased long-term mortality in patients less than 55 years old who have
      undergone knee replacement for osteoarthritis: results from the Swedish Knee
      Arthroplasty Register.
AB  - Patients with osteoarthritis undergoing knee replacement have been reported to
      have an overall reduced mortality compared with that of the general population.
      This has been attributed to the selection of healthier patients for surgery.
      However, previous studies have had a maximum follow-up time of ten years. We have
      used information from the Swedish Knee Arthroplasty Register to study the
      mortality of a large national series of patients with total knee replacement for
      up to 28 years after surgery and compared their mortality with that of the normal
      population. In addition, for a subgroup of patients operated on between 1980 and
      2002 we analysed their registered causes of death to determine if they differed
      from those expected. We found a reduced overall mortality during the first 12
      post-operative years after which it increased and became significantly higher
      than that of the general population. Age-specific analysis indicated an inverse
      correlation between age and mortality, where the younger the patients were, the
      higher their mortality. The shift at 12 years was caused by a relative over
      representation of younger patients with a longer follow-up. Analysis of specific
      causes of death showed a higher mortality for cardiovascular, gastrointestinal
      and urogenital diseases. The observation that early onset of osteoarthritis of
      the knee which has been treated by total knee replacement is linked to an
      increased mortality should be a reason for increased general awareness of health
      problems in these patients.

PMID- 17540744
TI  - Correlation of maximum flexion with clinical outcome after total knee replacement
      in Asian patients.
AB  - This study aimed to determine the correlation between the amount of maximum
      flexion and the clinical outcome in 207 Koreans (333 knees) undergoing total knee
      replacement. The association of maximum flexion with clinical outcome was
      evaluated one year postoperatively using three scoring systems; the American Knee
      Society score, Western Ontario McMaster Universities Osteoarthritis index and the
      Short Form-36. The mean maximum flexion decreased post-operatively at 12 months
      from 140.1 degrees (60 degrees to 160 degrees ) to 133.0 degrees (105 degrees to
      150 degrees ). Only the social function score of the Short Form-36 correlated
      significantly with maximum flexion (correlation coefficient = 0.180, p = 0.039).
      In comparative analyses of subgroups divided by a maximum flexion of 120 degrees
      , we found no significant differences in any parameters except the social
      function score of the Short Form-36 (41.9 vs 47.3, p = 0.031). Knees with a
      maximum flexion of more than 135 degrees had a better functional Western Ontario
      McMasters Universities Osteoarthritis index score than knees with maximum flexion
      of 135 degrees or less (17.5 vs 14.3, p = 0.031). We found only weak correlation
      between the postoperative maximum flexion and the clinical parameters for pain
      relief, function and quality of life, even in Korean patients. Efforts to
      increase post-operative maximum flexion should be exercised with caution until
      concerns relating to high-flexion activities are sufficiently resolved.

PMID- 17540745
TI  - A comparison of survival of moulded monoblock and modular tibial components of
      751 AGC total knee replacements in the treatment of rheumatoid arthritis.
AB  - We evaluated the survival of moulded monoblock and modular tibial components of
      the AGC total knee replacement in patients with rheumatoid arthritis. Between
      1985 and 1995, 751 knees with this diagnosis were replaced at our institution. A
      total of 256 tibial components were of the moulded design and 495 of the modular
      design. The mean follow-up of the moulded subgroup was 9.6 years (0.5 to 14.7),
      and that of the modular group 7.0 years (0.1 to 14.7). The groups differed
      significantly from each other in Larsen grade, cementing of components and
      patellar resurfacing, but no statistically significant difference between the
      survival of the components was found (Log rank test, p = 0.91). The cumulative
      success rate of the moulded group was 96.8% (95% confidence interval 93.6% to
      98.4%) at five years and 94.4% (95% confidence interval 90.4% to 96.7%) at ten
      years, and of the modular group 96.2% (95% confidence interval 94% to 97.6%) and
      93.6% (95% confidence interval 89.7% to 96%), respectively. Revision was required
      in 37 total knee replacements, the main causes were infection, pain, loosening of
      the tibial component and patellar problems. Survival rates for both components
      were satisfactory.

PMID- 17540746
TI  - Arthrodesis of the ankle in the presence of a large deformity in the coronal
      plane.
AB  - A consecutive series of 23 patients (25 ankles) with osteoarthritis of the ankle
      and severe varus or valgus deformity were treated by open arthrodesis using
      compression screws. Primary union was achieved in 24 ankles one required further
      surgery to obtain a solid fusion. The high level of satisfaction in this group of
      patients reinforces the view that open arthrodesis, as opposed to ankle
      replacement or arthroscopic arthrodesis, continues to be the treatment of choice
      when there is severe varus or valgus deformity associated with the arthritis.

PMID- 17540747
TI  - Improvement in abduction of the shoulder after reconstructive soft-tissue
      procedures in obstetric brachial plexus palsy.
AB  - Residual muscle weakness in obstetric brachial plexus palsy results in soft
      tissue contractures which limit the functional range of movement and lead to
      progressive glenoid dysplasia and joint instability. We describe the results of
      surgical treatment in 98 patients (mean age 2.5 years, 0.5 to 9.0) for the
      correction of active abduction of the shoulder. The patients underwent transfer
      of the latissimus dorsi and teres major muscles, release of contractures of
      subscapularis pectoralis major and minor, and axillary nerve decompression and
      neurolysis (the modified Quad procedure). The transferred muscles were sutured to
      the teres minor muscle, not to a point of bony insertion. The mean pre-operative
      active abduction was 45 degrees (20 degrees to 90 degrees ). At a mean follow-up
      of 4.8 years (2.0 to 8.7), the mean active abduction was 162 degrees (100 degrees
      to 180 degrees ) while 77 (78.6%) of the patients had active abduction of 160
      degrees or more. No decline in abduction was noted among the 29 patients (29.6%)
      followed up for six years or more. This procedure involving release of the
      contracted internal rotators of the shoulder combined with decompression and
      neurolysis of the axillary nerve greatly improves active abduction in young
      patients with muscle imbalance secondary to obstetric brachial plexus palsy.

PMID- 17540748
TI  - The factors affecting outcome after non-vascular bone grafting and internal
      fixation for nonunion of the scaphoid.
AB  - This study identified variables which influence the outcome of surgical
      management on 126 ununited scaphoid fractures managed by internal fixation and
      non-vascular bone grafting. The site of fracture was defined by a new method: the
      ratio of the length of the proximal fragment to the sum of the lengths of both
      fragments, calculated using specific views in the plain radiographs. Bone healing
      occurred in 71% (89) of cases. Only the site of nonunion (p = 1 x 10(-6)) and the
      delay to surgery (p = 0.001) remained significant on multivariate analysis. The
      effect of surgical delay on the probability of union increased as the fracture
      site moved proximally. A prediction model was produced by stepwise logistic
      regression analysis, enabling the surgeon to predict the success of surgery where
      the site of the nonunion and delay to surgery is known.

PMID- 17540749
TI  - In vivo measurement of tissue metabolism in tendons of the rotator cuff:
      implications for surgical management.
AB  - We have undertaken an in vivo assessment of the tissue metabolism and cellular
      activity in torn tendons of the rotator cuff. Cellular oxygen consumption was
      measured in 13 patients undergoing mini-open repair of small, medium, large and
      massive full-thickness tears. Measurements were also taken from three control
      patients who were undergoing open stabilisation of the shoulder with grossly
      normal tendons. The level of oxygen and nitrous oxide was measured
      amperometrically using silver needle microelectrodes at the apex of the tear and
      1.5 cm from its edge. With nitrous oxide indicating the degree of perfusion,
      oxygen consumption was calculated at each location to reflect cellular activity.
      All of the torn tendons had lower levels of cellular activity than the control
      group. This activity was lower still in the tissue nearest to the edge of the
      tear with the larger tears showing the lowest activity. This indicated reduced
      levels of tissue metabolism and infers a reduction in tendon viability. Our
      findings suggest that surgical repair of torn tendons of the rotator-cuff should
      include the more proximal, viable tissue, and may help to explain the high rate
      of re-rupture seen in larger tears.

PMID- 17540750
TI  - Alternating cervical laminoplasty for cervical spondylotic myelopathy.
AB  - We present a novel method of performing an 'open-door' cervical laminoplasty. The
      complete laminotomy is sited on alternate sides at successive levels, thereby
      allowing the posterior arch to be elevated to alternate sides. Foraminotomies can
      be carried out on either side to relieve root compression. The midline structures
      are preserved. We undertook this procedure in 23 elderly patients with a
      spondylotic myelopathy. Each was assessed clinically and radiologically before
      and after their operation. Follow-up was for a minimum of three years (mean 4.5
      years; 3 to 7). Using the modified Japanese Orthopaedic Association scoring
      system, the mean pre-operative score was 8.1 (6 to 10), which improved post
      operatively to a mean of 12.7 (11 to 14). The mean percentage improvement was 61%
      (50% to 85.7%) after three years. The canal/vertebral body ratio improved from a
      mean of 0.65 (0.33 to 0.73) pre-operatively to 0.94 (0.5 to 1.07)
      postoperatively. Alternating cervical laminoplasty can be performed safely in
      elderly patients with minimal morbidity and good results.

PMID- 17540751
TI  - Transmission of methicillin-resistant Staphylococcus aureus among hospital staff
      in a German trauma centre: a problem without a current solution?
AB  - Between October 2001 and February 2002, 324 healthcare workers were screened for
      methicillin-resistant Staphylococcus aureus (MRSA) by nose and throat swabs. A
      positive finding led to activation of a standardised control programme for the
      affected person who was immediately excluded from work. Family members of those
      who were MRSA-positive were offered screening free of charge. An eradication
      programme was carried out in the permanent carriers. MRSA was found in 17 (5.3%)
      healthcare workers, 11 of whom proved to be permanent carriers, and six
      temporarily colonised. Three children of a positive healthcare worker showed
      nasopharyngeal MRSA, the acquisition of which occurred within the hospital. The
      standardised eradication programme for carriers was successful in most cases but
      failed in two individuals, whereupon systemic antibiotics were used successfully.
      The decolonised carriers, observed for more than one year, remained MRSA
      negative. Isolation precautions in hospitals do not always prevent hospital staff
      and their families from acquiring MRSA. The identification of affected employees
      is difficult because in most cases only asymptomatic colonisation occurs.
      Screening and eradication can be complicated and costly, and for the affected
      employees the occupational consequences can be far-reaching as they have no
      guaranteed legal protection.

PMID- 17540752
TI  - Treatment of displaced supracondylar fractures of the humerus in children by a
      pin leverage technique.
AB  - This study aimed to evaluate the use of pin leverage in the reduction of Gartland
      type III supracondylar fractures of the humerus in children. The study comprised
      95 children, who were split into three groups according to the type of method of
      reduction used. Group 1, had an open reduction, group 2, had closed reduction and
      percutaneous pin fixation and group 3, the pin leverage technique. Each group was
      analysed according to the time to surgery, the duration of the procedure, the
      incidence of complications, and the clinical and radiological outcome. The mean
      duration of the operative procedure in groups 1, 2 and 3 was 119 minutes (80 to
      235), 57 minutes (20 to 110) and 68 minutes (30 to 90), respectively. At a mean
      follow-up of 30 months (12 to 63) the clinical results were declared excellent or
      good in all children and the radiological results intermediate in five patients
      in group 2. The results of the closed reduction using the pin leverage technique
      was classified as failure in two children. Our findings lead us to believe that
      the pin leverage method of reduction gives good results in the treatment of
      Gartland type III fractures.

PMID- 17540753
TI  - Crescent fracture-dislocation of the sacroiliac joint: a functional
      classification.
AB  - Crescent fracture dislocations are a well-recognised subset of pelvic ring
      injuries which result from a lateral compression force. They are characterised by
      disruption of the sacroiliac joint and extend proximally as a fracture of the
      posterior iliac wing. We describe a classification with three distinct types.
      Type I is characterised by a large crescent fragment and the dislocation
      comprises no more than one-third of the sacroiliac joint, which is typically
      inferior. Type II fractures are associated with an intermediate-size crescent
      fragment and the dislocation comprises between one- and two-thirds of the joint.
      Type III fractures are associated with a small crescent fragment where the
      dislocation comprises most, but not all of the joint. The principal goals of
      surgical intervention are the accurate and stable reduction of the sacroiliac
      joint. This classification proves useful in the selection of both the surgical
      approach and the reduction technique. A total of 16 patients were managed
      according to this classification and achieved good functional results
      approximately two years from the time of the index injury. Confounding factors
      compromise the summary short-form-36 and musculoskeletal functional assessment
      instrument scores, which is a well-recognised phenomenon when reporting the
      outcome of high-energy trauma.

PMID- 17540754
TI  - Construct validity of the Enneking score for measuring function in patients with
      malignant or aggressive benign tumours of the upper limb.
AB  - We evaluated the construct validity of the Musculoskeletal Tumour Society rating
      scale (Enneking score) as a functional measure for patients with sarcoma
      involving the upper limb. We compared the Enneking score by examining the
      correlation between two patient-derived outcome measures, the Disability of the
      Arm, Shoulder, and Hand (DASH) questionnaire and the Medical Outcomes Study Short
      Form-36 (SF-36) as indicators of functional status in 40 patients with malignant
      or aggressive benign bone and soft-tissue tumours of the upper limb who had
      undergone surgical treatment. The frequency distributions were similar among the
      three scoring systems. As for the validity, Spearman's rank correlation
      coefficient of the Enneking score to the DASH questionnaire was -0.79 and that of
      the Enneking to the SF-36 subscales ranged from 0.38 to 0.60. Despite being a
      measure from the surgeon's perspective, the Enneking score was shown to be a
      valid indicator of physical disability in patients with malignant or aggressive
      benign tumours of the upper limb and reflected their opinion.

PMID- 17540755
TI  - Tuberculous arthritis of the knee with Staphylococcus superinfection.
AB  - We describe a case of septic arthritis of the knee in which the diagnosis of
      tuberculosis was masked by an initial culture growth of Staphylococcus aureus.
      This led to a delay in diagnosis and an adverse outcome. In the appropriate
      clinical setting, we suggest that the index of suspicion for skeletal
      tuberculosis be raised in developed countries in order to avoid diagnostic delay,
      by requesting cultures for acid-fast bacilli and synovial biopsies at
      arthroscopy. Moreover, antituberculosis therapy should be started whilst awaiting
      the results of culture if the clinical history and biopsies are strongly
      suggestive of the diagnosis.

PMID- 17540756
TI  - A history of osteomyelitis from the Journal of Bone and Joint Surgery: 1948 TO
      2006.
AB  - Osteomyelitis is one of the oldest diseases known. It took many years before the
      acute infection could be brought under control with antibiotics and chronic
      osteomyelitis remains difficult to manage. The modern history of the disease is
      reflected in the pages of the Journal of Bone and Joint Surgery.

PMID- 17540757
TI  - Genetic modification of chondrocytes with insulin-like growth factor-1 enhances
      cartilage healing in an equine model.
AB  - Gene therapy with insulin-like growth factor-1 (IGF-1) increases matrix
      production and enhances chondrocyte proliferation and survival in vitro. The
      purpose of this study was to determine whether arthroscopically-grafted
      chondrocytes genetically modified by an adenovirus vector encoding equine IGF-1
      (AdIGF-1) would have a beneficial effect on cartilage healing in an equine
      femoropatellar joint model. A total of 16 horses underwent arthroscopic repair of
      a single 15 mm cartilage defect in each femoropatellar joint. One joint received
      2 x 10(7) AdIGF-1 modified chondrocytes and the contralateral joint received 2 x
      10(7) naive (unmodified) chondrocytes. Repairs were analysed at four weeks, nine
      weeks and eight months after surgery. Morphological and histological appearance,
      IGF-1 and collagen type II gene expression (polymerase chain reaction, in situ
      hybridisation and immunohistochemistry), collagen type II content (cyanogen
      bromide and sodium dodecyl sulphate-polyacrylamide gel electrophoresis),
      proteoglycan content (dimethylmethylene blue assay), and gene expression for
      collagen type I, matrix metalloproteinase (MMP)-1, MMP-3, MMP-13, aggrecanase-1,
      tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) and TIMP-3 were
      evaluated. Genetic modification of chondrocytes significantly increased IGF-1
      mRNA and ligand production in repair tissue for up to nine weeks following
      transplantation. The gross and histological appearance of IGF-1 modified repair
      tissue was improved over control defects. Gross filling of defects was
      significantly improved at four weeks, and a more hyaline-like tissue covered the
      lesions at eight months. Histological outcome at four and nine weeks post
      transplantation revealed greater tissue filling of defects transplanted with
      genetically modified chondrocytes, whereas repair tissue in control defects was
      thin and irregular and more fibrous. Collagen type II expression in IGF-1 gene
      transduced defects was increased 100-fold at four weeks and correlated with
      increased collagen type II immunoreaction up to eight months. Genetic
      modification of chondrocytes with AdIGF-1 prior to transplantation improved early
      (four to nine weeks), and to a lesser degree long-term, cartilage healing in the
      equine model. The equine model of cartilage healing closely resembles human
      clinical cartilage repair. The results of this study suggest that cartilage
      healing can be enhanced through genetic modification of chondrocytes prior to
      transplantation.

PMID- 17540758
TI  - Vibration-assisted bone-graft compaction in impaction bone grafting of the femur.
AB  - The complications of impaction bone grafting in revision hip replacement includes
      fracture of the femur and subsidence of the prosthesis. In this in vitro study we
      aimed to investigate whether the use of vibration, combined with a perforated
      tamp during the compaction of morsellised allograft would reduce peak loads and
      hoop strains in the femur as a surrogate marker of the risk of fracture and
      whether it would also improve graft compaction and prosthetic stability. We found
      that the peak loads and hoop strains transmitted to the femoral cortex during
      graft compaction and subsidence of the stem in subsequent mechanical testing were
      reduced. This innovative technique has the potential to reduce the risk of intra
      operative fracture and to improve graft compaction and therefore prosthetic
      stability.

PMID- 17540759
TI  - Healing of full-thickness defects of the articular cartilage in rabbits using
      fibroblast growth factor-2 and a fibrin sealant.
AB  - We have investigated in vitro the release kinetics and bioactivity of fibroblast
      growth factor-2 (FGF-2) released from a carrier of fibrin sealant. In order to
      evaluate the effects of the FGF-2 delivery mechanism on the repair of articular
      cartilage, full-thickness cylindrical defects, 5 mm in diameter and 4 mm in
      depth, which were too large to undergo spontaneous repair, were created in the
      femoral trochlea of rabbit knees. These defects were then filled with the
      sealant. Approximately 50% of the FGF-2 was released from the sealant within 24
      hours while its original bioactivity was maintained. The implantation of the
      fibrin sealant incorporating FGF-2 successfully induced healing of the surface
      with hyaline cartilage and concomitant repair of the subchondral bone at eight
      weeks after the creation of the defect. Our findings suggest that this delivery
      method for FGF-2 may be useful for promoting regenerative repair of full
      thickness defects of articular cartilage in humans.

PMID- 17540760
TI  - Factors affecting the stability of screws in human cortical osteoporotic bone: a
      cadaver study.
AB  - We investigated several factors which affect the stability of cortical screws in
      osteoporotic bone using 18 femora from cadavers of women aged between 45 and 96
      years (mean 76). We performed bone densitometry to measure the bone mineral
      density of the cortical and cancellous bone of the shaft and head of the femur,
      respectively. The thickness and overall bone mass of the cortical layer of the
      shaft of the femur were measured using a microCT scanner. The force required to
      pull-out a 3.5 mm titanium cortical bone screw was determined after standardised
      insertion into specimens of the cortex of the femoral shaft. A significant
      correlation was found between the pull-out strength and the overall bone mass of
      the cortical layer (r(2) = 0.867, p < 0.01) and also between its thickness (r(2)
      = 0.826, p < 0.01) and bone mineral density (r(2) = 0.861, p < 0.01). There was
      no statistically significant correlation between the age of the donor and the
      pull-out force (p = 0.246), the cortical thickness (p = 0.199), the bone mineral
      density (p = 0.697) or the level of osteoporosis (p = 0.378). We conclude that
      the overall bone mass, the thickness and the bone mineral density of the cortical
      layer, are the main factors which affect the stability of a screw in human female
      osteoporotic cortical bone.

PMID- 17540761
TI  - Re: The floating shoulder.

PMID- 17540762
TI  - ABCA3 is critical for lamellar body biogenesis in vivo.
AB  - Mutations in ATP-binding cassette transporter A3 (human ABCA3) protein are
      associated with fatal respiratory distress syndrome in newborns. We therefore
      characterized mice with targeted disruption of the ABCA3 gene. Homozygous Abca3-/
      knock-out mice died soon after birth, whereas most of the wild type, Abca3+/+,
      and heterozygous, Abca3+/-, neonates survived. The lungs from E18.5 and E19.5
      Abca3-/- mice were less mature than wild type. Alveolar type 2 cells from Abca3-/
      embryos contained no lamellar bodies, and expression of mature SP-B protein was
      disrupted when compared with the normal lung surfactant system of wild type
      embryos. Small structural and functional differences in the surfactant system
      were seen in adult Abca3+/- compared with Abca3+/+ mice. The heterozygotes had
      fewer lamellar bodies, and the incorporation of radiolabeled substrates into
      newly synthesized disaturated phosphatidylcholine, phosphatidylglycerol,
      phosphatidylethanolamine, and phosphatidylserine in both lamellar bodies and
      surfactant was lower than in Abca3+/+ mouse lungs. In addition, since the
      fraction of near term Abca3-/- embryos was significantly lower than expected from
      Mendelian inheritance ABCA3 probably plays roles in development unrelated to
      surfactant. Collectively, these findings strongly suggest that ABCA3 is necessary
      for lamellar body biogenesis, surfactant protein-B processing, and lung
      development late in gestation.

PMID- 17540763
TI  - Ca2+-dependent activator protein for secretion 1 is critical for constitutive and
      regulated exocytosis but not for loading of transmitters into dense core
      vesicles.
AB  - Although CAPS1 was originally identified as a soluble factor that reconstitutes
      Ca(2+)-dependent secretion from permeabilized neuroendocrine cells, its exact
      function in intact mammalian cells remains controversial. Here we investigate the
      role for CAPS1 by generating stable cell lines in which CAPS1 is strongly down
      regulated. In these cells, Ca(2+)-dependent secretion was strongly reduced not
      only of catecholamine but also of a transfected neuropeptide. These secretion
      defects were rescued by infusion of CAPS1-containing brain cytosol or by
      transfection-mediated expression of CAPS1. Whole cell patch clamp recording
      revealed significant reductions in slow burst and sustained release components of
      exocytosis in the knockdown cells. Unexpectedly, they also accumulated higher
      amounts of endogenous and exogenous transmitters, which were attributable to
      reductions in constitutive secretion. Electron microscopy did not reveal
      abnormalities in the number or docking of dense core vesicles. Our results
      indicate that CAPS1 plays critical roles not only in Ca(2+)-dependent, regulated
      exocytosis but also in constitutive exocytosis downstream of vesicle docking.
      However, they do not support the role for CAPS1 in loading transmitters into
      dense core vesicles.

PMID- 17540764
TI  - Selective desensitization of growth factor signaling by cell adhesion to
      fibronectin.
AB  - Cell adhesion to the extracellular matrix is required to execute growth factor
      (GF)-mediated cell behaviors, such as proliferation. A major underlying mechanism
      is that cell adhesion enhances GF-mediated intracellular signals, such as
      extracellular signal-regulated kinase (Erk). However, because GFs use distinct
      mechanisms to activate Ras-Erk signaling, it is unclear whether adhesion-mediated
      enhancement of Erk signaling is universal to all GFs. We examined this issue by
      quantifying the dynamics of Erk signaling induced by epidermal growth factor,
      basic fibroblast growth factor (bFGF), and platelet-derived growth factor (PDGF)
      in NIH-3T3 fibroblasts. Adhesion to fibronectin-coated surfaces enhances Erk
      signaling elicited by epidermal growth factor but not by bFGF or PDGF.
      Unexpectedly, adhesion is not always a positive influence on GF-mediated
      signaling. At critical subsaturating doses of PDGF or bFGF, cell adhesion ablates
      Erk signaling; that is, adhesion desensitizes the cell to GF stimulation,
      rendering the signaling pathway unresponsive to GF. Interestingly, the timing of
      growth factor stimulation proved critical to the desensitization process. Erk
      activation significantly improved only when pre-exposure to adhesion was
      completely eliminated; thus, concurrent stimulation by GF and adhesion was able
      to partially rescue adhesion-mediated desensitization of PDGF- and bFGF-mediated
      Erk and Akt signaling. These findings suggest that adhesion-mediated
      desensitization occurs with rapid kinetics and targets a regulatory point
      upstream of Ras and proximal to GF receptor activation. Thus, adhesion-dependent
      Erk signaling is not universal to all GFs but, rather, is GF-specific with
      quantitative features that depend strongly on the dose and timing of GF exposure.

PMID- 17540765
TI  - Phospholipase D1 production of phosphatidic acid at the plasma membrane promotes
      exocytosis of large dense-core granules at a late stage.
AB  - Substantial efforts have recently been made to demonstrate the importance of
      lipids and lipid-modifying enzymes in various membrane trafficking processes,
      including calcium-regulated exocytosis of hormones and neurotransmitters. Among
      bioactive lipids, phosphatidic acid (PA) is an attractive candidate to promote
      membrane fusion through its ability to change membrane topology. To date,
      however, the biosynthetic pathway, the dynamic location, and actual function of
      PA in secretory cells remain unknown. Using a short interference RNA strategy on
      chromaffin and PC12 cells, we demonstrate here that phospholipase D1 is activated
      in secretagogue-stimulated cells and that it produces PA at the plasma membrane
      at the secretory granule docking sites. We show that phospholipase D1 activation
      and PA production represent key events in the exocytotic progression. Membrane
      capacitance measurements indicate that reduction of endogenous PA impairs the
      formation of fusion-competent granules. Finally, we show that the PLD1 short
      interference RNA-mediated inhibition of exocytosis can be rescued by exogenous
      provision of a lipid that favors the transition of opposed bi-layer membranes to
      hemifused membranes having the outer leaflets fused. Our findings demonstrate
      that PA synthesis is required during exocytosis to facilitate a late event in the
      granule fusion pathway. We propose that the underlying mechanism is related to
      the ability of PA to alter membrane curvature and promote hemi-fusion.

PMID- 17540766
TI  - Sequential opening of mitochondrial ion channels as a function of glutathione
      redox thiol status.
AB  - Mitochondrial membrane potential (DeltaPsi(m)) depolarization contributes to cell
      death and electrical and contractile dysfunction in the post-ischemic heart. An
      imbalance between mitochondrial reactive oxygen species production and scavenging
      was previously implicated in the activation of an inner membrane anion channel
      (IMAC), distinct from the permeability transition pore (PTP), as the first
      response to metabolic stress in cardiomyocytes. The glutathione redox couple,
      GSH/GSSG, oscillated in parallel with DeltaPsi(m) and the NADH/NAD(+) redox
      state. Here we show that depletion of reduced glutathione is an alternative
      trigger of synchronized mitochondrial oscillation in cardiomyocytes and that
      intermediate GSH/GSSG ratios cause reversible DeltaPsi(m) depolarization,
      although irreversible PTP activation is induced by extensive thiol oxidation.
      Mitochondrial dysfunction in response to diamide occurred in stages, progressing
      from oscillations in DeltaPsi(m) to sustained depolarization, in association with
      depletion of GSH. Mitochondrial oscillations were abrogated by 4'-chlorodiazepam,
      an IMAC inhibitor, whereas cyclosporin A was ineffective. In saponin
      permeabilized cardiomyocytes, the thiol redox status was systematically clamped
      at GSH/GSSG ratios ranging from 300:1 to 20:1. At ratios of 150:1-100:1,
      DeltaPsi(m) depolarized reversibly, and a matrix-localized fluorescent marker was
      retained; however, decreasing the GSH/GSSG to 50:1 irreversibly depolarized
      DeltaPsi(m) and induced maximal rates of reactive oxygen species production,
      NAD(P)H oxidation, and loss of matrix constituents. Mitochondrial GSH sensitivity
      was altered by inhibiting either GSH uptake, the NADPH-dependent glutathione
      reductase, or the NADH/NADPH transhydrogenase, indicating that matrix GSH
      regeneration or replenishment was crucial. The results indicate that GSH/GSSG
      redox status governs the sequential opening of mitochondrial ion channels (IMAC
      before PTP) triggered by thiol oxidation in cardiomyocytes.

PMID- 17540767
TI  - Retinoic acid-inducible gene-I and interferon-beta promoter stimulator-1 augment
      proapoptotic responses following mammalian reovirus infection via interferon
      regulatory factor-3.
AB  - During viral infection, cells initiate antiviral responses to contain replication
      and inhibit virus spread. One protective mechanism involves activation of
      transcription factors interferon regulatory factor-3 (IRF-3) and NF-kappaB,
      resulting in secretion of the antiviral cytokine, interferon-beta. Another is
      induction of apoptosis, killing the host cell before virus disseminates.
      Mammalian reovirus induces both interferon-beta and apoptosis, raising the
      possibility that both pathways are initiated by a common cellular sensor. We show
      here that reovirus activates IRF-3 with kinetics that parallel the activation of
      NF-kappaB, a known mediator of reovirus-induced apoptosis. Activation of IRF-3
      requires functional retinoic acid inducible gene-I and interferon-beta promoter
      stimulator-1, but these intracellular sensors are dispensable for activation of
      NF-kappaB. Interferon-beta promoter stimulator-1 and IRF-3 are required for
      efficient apoptosis following reovirus infection, suggesting a common mechanism
      of antiviral cytokine induction and activation of the cell death response.

PMID- 17540768
TI  - Mitochondrial reactive oxygen species signal hepatocyte steatosis by regulating
      the phosphatidylinositol 3-kinase cell survival pathway.
AB  - Abnormal dietary intake of macronutrients is implicated in the development of
      obesity and fatty liver disease. Steatosis develops in cultured hepatocytes
      exposed to medium containing either a high concentration of long chain free fatty
      acids (HFFA) or medium deficient in methionine and choline (MCD). This study
      examined the mitochondrial reactive oxygen species (ROS)-dependent regulation of
      the phosphoinositol (PI) 3-kinase pathway in steatosis induced by exposure of AML
      12 mouse hepatocytes to MCD or HFFA medium. Exposure to either MCD or HFFA medium
      resulted in increased production of superoxide anions and H(2)O(2), transduction
      of the PI 3-kinase pathway and steatosis. Inhibition of PI 3-kinase with LY294002
      prevented steatosis. Pharmacologically inhibiting electron transport chain
      complex III production of ROS prevented activation of PI 3-kinase during
      macronutrient perturbation, whereas pharmacologically promoting electron
      transport chain complex III ROS production activated PI 3-kinase independent of
      nutrient input. The data suggest that H(2)O(2) is the ROS species involved in
      signal transduction; promoting the rapid conversion of superoxide to H(2)O(2)
      does not inhibit PI 3-kinase pathway activation during nutrient perturbation, and
      exogenous H(2)O(2) activates it independent of nutrient input. In addition to
      transducing PI 3-kinase, the ROS-dependent signal cascade amplifies the PI 3
      kinase signal by maintaining phosphatase and tensin homolog in its inactive
      phosphorylated state. Knockdown of phosphatase and tensin homolog by small
      interfering RNA independently activated the PI 3-kinase pathway. Our findings
      suggest a common path for response to altered nutrition involving mitochondrial
      ROS-dependent PI 3-kinase pathway regulation, leading to steatosis.

PMID- 17540769
TI  - Structural mechanism for substrate inhibition of the adenosine 5'-phosphosulfate
      kinase domain of human 3'-phosphoadenosine 5'-phosphosulfate synthetase 1 and its
      ramifications for enzyme regulation.
AB  - In mammals, the universal sulfuryl group donor molecule 3'-phosphoadenosine 5'
      phosphosulfate (PAPS) is synthesized in two steps by a bifunctional enzyme called
      PAPS synthetase. The APS kinase domain of PAPS synthetase catalyzes the second
      step in which APS, the product of the ATP-sulfurylase domain, is phosphorylated
      on its 3'-hydroxyl group to yield PAPS. The substrate APS acts as a strong
      uncompetitive inhibitor of the APS kinase reaction. We generated truncated and
      point mutants of the APS kinase domain that are active but devoid of substrate
      inhibition. Structural analysis of these mutant enzymes reveals the intrasubunit
      rearrangements that occur upon substrate binding. We also observe intersubunit
      rearrangements in this dimeric enzyme that result in asymmetry between the two
      monomers. Our work elucidates the structural elements required for the ability of
      the substrate APS to inhibit the reaction at micromolar concentrations. Because
      the ATP-sulfurylase domain of PAPS synthetase influences these elements in the
      APS kinase domain, we propose that this could be a communication mechanism
      between the two domains of the bifunctional enzyme.

PMID- 17540770
TI  - Heparan sulfate degradation products can associate with oxidized proteins and
      proteasomes.
AB  - The S-nitrosylated proteoglycan glypican-1 recycles via endosomes where its
      heparan sulfate chains are degraded into anhydromannose-containing saccharides by
      NO-catalyzed deaminative cleavage. Because heparan sulfate chains can be
      associated with intracellular protein aggregates, glypican-1 autoprocessing may
      be involved in the clearance of misfolded recycling proteins. Here we have
      arrested and then reactivated NO-catalyzed cleavage in the absence or presence of
      proteasome inhibitors and analyzed the products present in endosomes or co
      precipitating with proteasomes using metabolic radiolabeling and immunomagnet
      isolation as well as by confocal immunofluorescence microscopy. Upon reactivation
      of deaminative cleavage in T24 carcinoma cells, [(35)S]sulfate-labeled
      degradation products appeared in Rab7-positive vesicles and co-precipitated with
      a 20 S proteasome subunit. Simultaneous inhibition of proteasome activity
      resulted in a sustained accumulation of degradation products. We also
      demonstrated that the anhydromannose-containing heparan sulfate degradation
      products are detected by a hydrazide-based method that also identifies oxidized,
      i.e. carbonylated, proteins that are normally degraded in proteasomes. Upon
      inhibition of proteasome activity, pronounced colocalization between carbonyl
      staining, anhydro-mannose-containing degradation products, and proteasomes was
      observed in both T24 carcinoma and N2a neuroblastoma cells. The deaminatively
      generated products that co-precipitated with the proteasomal subunit contained
      heparan sulfate but were larger than heparan sulfate oligosaccharides and
      resistant to both acid and alkali. However, proteolytic degradation released
      heparan sulfate oligosaccharides. In Niemann-Pick C-1 fibroblasts, where
      deaminative degradation of heparan sulfate is defective, carbonylated proteins
      were abundant. Moreover, when glypican-1 expression was silenced in normal
      fibroblasts, the level of carbonylated proteins increased raising the possibility
      that deaminative heparan sulfate degradation is involved in the clearance of
      misfolded proteins.

PMID- 17540771
TI  - Hyaluronan export by the ABC transporter MRP5 and its modulation by intracellular
      cGMP.
AB  - Hyaluronan must be exported from its site of synthesis, the inner side of plasma
      membrane, to the extracellular matrix. Here, we identified the multidrug
      associated protein MRP5 as the principle hyaluronan exporter from fibroblasts.
      The expression of the MRP5 (ABC-C5) transporter was silenced in fibroblasts using
      RNA interference, and a dose-dependent inhibition of hyaluronan export was
      observed. Hyaluronan oligosaccharides introduced into the cytosol competed with
      the export of endogenously labeled hyaluronan and the MRP5 substrate fluorescein.
      Because cGMP is a physiological substrate of MRP5, the intracellular
      concentrations of cGMP were modulated by the drugs 3-isobutyl-1-methylxanthin,
      propentofyllin, L-NAME, zaprinast, and bromo-cGMP, and the effects on hyaluronan
      export were analyzed. Increasing the cGMP levels inhibited hyaluronan export and
      decreasing it afforded higher concentrations of zaprinast to inhibit the export.
      Thus, cGMP may be a physiological regulator of hyaluronan export at the level of
      the export MRP5.

PMID- 17540772
TI  - Evidence that the heme regulatory motifs in heme oxygenase-2 serve as a
      thiol/disulfide redox switch regulating heme binding.
AB  - Heme oxygenase (HO) catalyzes the O(2)- and NADPH-dependent conversion of heme to
      biliverdin, CO, and iron. The two forms of HO (HO-1 and HO-2) share similar
      physical properties but are differentially regulated and exhibit dissimilar
      physiological roles and tissue distributions. Unlike HO-1, HO-2 contains heme
      regulatory motifs (HRMs) (McCoubrey, W. K., Jr., Huang, T. J., and Maines, M. D.
      (1997) J. Biol. Chem. 272, 12568-12574). Here we describe UV-visible, EPR, and
      differential scanning calorimetry experiments on human HO-2 variants containing
      single, double, and triple mutations in the HRMs. Oxidized HO-2, which contains
      an intramolecular disulfide bond linking Cys(265) of HRM1 and Cys(282) of HRM2,
      binds heme tightly. Reduction of the disulfide bond increases the K(d) for ferric
      heme from 0.03 to 0.3 microm, which is much higher than the concentration of the
      free heme pool in cells. Although the HRMs markedly affect the K(d) for heme,
      they do not alter the k(cat) for heme degradation and do not bind additional
      hemes. Because HO-2 plays a key role in CO generation and heme homeostasis,
      reduction of the disulfide bond would be expected to increase intracellular free
      heme and decrease CO concentrations. Thus, we propose that the HRMs in HO-2
      constitute a thiol/disulfide redox switch that regulates the myriad physiological
      functions of HO-2, including its involvement in the hypoxic response in the
      carotid body, which involves interactions with a Ca(2+)-activated potassium
      channel.

PMID- 17540773
TI  - The interaction of endoglin with beta-arrestin2 regulates transforming growth
      factor-beta-mediated ERK activation and migration in endothelial cells.
AB  - In endothelial cells, transforming growth factor beta (TGF-beta) signals through
      two distinct pathways to regulate endothelial cell proliferation and migration,
      the ALK-1/Smads 1/5/8 pathway and the ALK-5/Smads 2/3 pathway. TGF-beta signaling
      through these pathways is further regulated in endothelial cells by the
      endothelial specific TGF-beta superfamily co-receptor, endoglin. The importance
      of endoglin, ALK-1, and ALK-5 in endothelial biology is underscored by the
      embryonic lethal phenotypes of knock-outs in mice due to defects in angiogenesis,
      and by the presence of disease-causing mutations in these genes in human vascular
      diseases. However, the mechanism of action of endoglin is not well defined. Here
      we define a novel interaction between endoglin and the scaffolding protein beta
      arrestin2. Both co-immunoprecipitation and fluorescence confocal studies
      demonstrate the specific interaction between endoglin and beta-arrestin2 in
      endothelial cells, enhanced by ALK-1 and to a lesser extent by the type II TGF
      beta receptor. The endoglin/beta-arrestin2 interaction results in endoglin
      internalization and co-accumulation of endoglin and beta-arrestin2 in endocytic
      vesicles. Whereas endoglin did not have a direct impact on either Smad 2/3 or
      Smad 1/5/8 activation, endoglin antagonized TGF-beta-mediated ERK signaling,
      altered the subcellular distribution of activated ERK, and inhibited endothelial
      cell migration in a manner dependent on the ability of endoglin to interact with
      beta-arrestin2. Reciprocally, small interfering RNA-mediated silencing of
      endogenous beta-arrestin2 expression restored TGF-beta-mediated ERK activation
      and increased endothelial cell migration in an endoglin-dependent manner. These
      studies define a novel function for endoglin, and further expand the roles
      mediated by the ubiquitous scaffolding protein beta-arrestin2.

PMID- 17540774
TI  - CCAAT enhancer-binding protein beta regulates constitutive gene expression during
      late stages of monocyte to macrophage differentiation.
AB  - Human monocyte to macrophage differentiation is accompanied by pronounced
      phenotypical changes and generally proceeds in the absence of proliferation. The
      molecular events governing this process are poorly understood. Here, we studied
      the regulation of the macrophage-specific chitotriosidase (CHIT1) gene promoter
      to gain insights into the mechanisms of transcriptional control during the
      differentiation of human blood monocytes into macrophages. We used transient
      transfections to define a cell type-specific minimal promoter that was mainly
      dependent on a proximal C/EBP motif that bound multiple C/EBP factors in gel
      shift assays. In depth analysis of occupied promoter elements using in vivo
      footprinting and chromatin immunoprecipitation analyses demonstrated the
      differentiation-associated recruitment of C/EBPbeta and PU.1 at the proximal
      promoter in parallel with CHIT1 mRNA induction. Notably, the induction of
      C/EBPbeta promoter binding strongly correlated with increased nuclear levels of
      Thr-235-phosphorylated C/EBPbeta protein during the differentiation process,
      whereas C/EBPbeta mRNA and total protein expression remained relatively stable.
      Our data suggest an important constitutive gene regulatory function for C/EBPbeta
      in differentiated macrophages but not in human blood monocytes.

PMID- 17540775
TI  - Plasminogen activator inhibitor-1 is an inhibitor of factor VII-activating
      protease in patients with acute respiratory distress syndrome.
AB  - Factor VII-activating protease (FSAP) is a novel plasma-derived serine protease
      structurally homologous to tissue-type and urokinase-type plasminogen activators.
      We demonstrate that plasminogen activator inhibitor-1 (PAI-1), the predominant
      inhibitor of tissue-type and urokinase-type plasminogen activators in plasma and
      tissues, is an inhibitor of FSAP as well. We detected PAI-1.FSAP complexes in
      addition to high levels of extracellular RNA, an important FSAP cofactor, in
      bronchoalveolar lavage fluids from patients with acute respiratory distress
      syndrome. Hydrolytic activity of FSAP was inhibited by PAI-1 with a second-order
      inhibition rate constant (K(a)) of 3.38 +/- 1.12 x 10(5) m(-1).s(-1). Residue
      Arg(346) was a critical recognition element on PAI-1 for interaction with FSAP.
      RNA, but not DNA, fragments (>400 nucleotides in length) dramatically enhanced
      the reactivity of PAI-1 with FSAP, and 4 microg.ml(-1) RNA increased the K(a) to
      1.61 +/- 0.94 x 10(6) m(-1).s(-1). RNA also stabilized the active conformation of
      PAI-1, increasing the half-life for spontaneous conversion of active to latent
      PAI-1 from 48.4 +/- 8 min to 114.6 +/- 5 min. In contrast, little effect of DNA
      on PAI-1 stability was apparent. Residues Arg(76) and Lys(80) in PAI-1 were key
      elements mediating binding of nucleic acids to PAI-1. FSAP-driven inhibition of
      vascular smooth muscle cell proliferation was antagonized by PAI-1, suggesting
      functional consequences for the FSAP-PAI-1 interaction. These data indicate that
      extracellular RNA and PAI-1 can regulate FSAP activity, thereby playing a
      potentially important role in hemostasis and cell functions under various
      pathophysiological conditions, such as acute respiratory distress syndrome.

PMID- 17540776
TI  - Synapse specificity of calcium release probed by chemical two-photon uncaging of
      inositol 1,4,5-trisphosphate.
AB  - Biological messengers can be "caged" by adding a single photosensitive group that
      can be photolyzed by a light flash to achieve spatially and temporally precise
      biochemical control. Here we report that photolysis of a double-caged form of the
      second messenger inositol 1,4,5-trisphosphate (IP3) triggers focal calcium
      release in Purkinje cell somata, dendrites, and spines as measured by two-photon
      microscopy. In calbindin knock-out Purkinje cells, peak calcium increased with
      flash energy with higher cooperativity for double-caged IP3 than for conventional
      single-caged IP3, consistent with a chemical two-photon effect. Spine photolysis
      of double-caged IP3 led to local calcium release. Uncaging of glycerophosphoryl
      myo-inositol 4,5-bisphosphate (gPIP2), a poorly metabolizable IP3 analog, led to
      less well localized release. Thus, IP3 breakdown is necessary for spine
      specificity. IP3- and gPIP2-evoked signals declined from peak with similar, slow
      time courses, indicating that release lasts hundreds of milliseconds and is
      terminated not by IP3 degradation but by intrinsic receptor dynamics. Based on
      measurements of spine-dendrite coupling, IP3-evoked calcium signals are expected
      to be at least 2.4-fold larger in their spine of origin than in nearby spines,
      allowing IP3 to act as a synapse-specific second messenger. Unexpectedly, single
      caged IP3 led to less release in somata and was ineffective in dendrites and
      spines. Calcium release using caged gPIP2 was inhibited by the addition of single
      caged IP3, suggesting that single-caged IP3 is an antagonist of calcium release.
      Caging at multiple sites may be an effective general approach to reducing
      residual receptor interaction.

PMID- 17540777
TI  - alphavbeta5 integrin sustains growth of human pre-B cells through an RGD
      independent interaction with a basic domain of the CD23 protein.
AB  - CD23 is a type II transmembrane glycoprotein synthesized by hematopoietic cells
      that has biological activity in both membrane-bound and freely soluble forms,
      acting via a number of receptors, including integrins. We demonstrate here that
      soluble CD23 (sCD23) sustains growth of human B cell precursors via an RGD
      independent interaction with the alphavbeta5 integrin. The integrin recognizes a
      tripeptide motif in a small disulfide-bonded loop at the N terminus of the lectin
      head region of CD23, centered around Arg(172), Lys(173), and Cys(174) (RKC). This
      RKC motif is present in all forms of sCD23 with cytokine-like activity, and
      cytokine activity is independent of the lectin head, an "inverse RGD" motif, and
      the CD21 and IgE binding sites. RKC-containing peptides derived from this region
      of CD23 bind alphavbeta5 and are biologically active. The binding and activity of
      these peptides is unaffected by inclusion of a short peptide containing the
      classic RGD sequence recognized by integrins, and, in far-Western analyses, RKC
      containing peptides bind to the beta subunit of the alphavbeta5 integrin. The
      interaction between alphavbeta5 and sCD23 indicates that integrins deliver to
      cells important signals initiated by soluble ligands without the requirement for
      interactions with RGD motifs in their common ligands. This mode of integrin
      signaling may not be restricted to alphavbeta5.

PMID- 17540778
TI  - Different T cell receptor affinity thresholds and CD8 coreceptor dependence
      govern cytotoxic T lymphocyte activation and tetramer binding properties.
AB  - T cells have evolved a unique system of ligand recognition involving an antigen T
      cell receptor (TCR) and a coreceptor that integrate stimuli provided by the
      engagement of peptide-major histocompatibility complex (pMHC) antigens. Here, we
      use altered pMHC class I (pMHCI) molecules with impaired CD8 binding (CD8-null)
      to quantify the contribution of coreceptor extracellular binding to (i) the
      engagement of soluble tetrameric pMHCI molecules, (ii) the kinetics of TCR/pMHCI
      interactions on live cytotoxic T lymphocytes (CTLs), and (iii) the activation of
      CTLs by cell-surface antigenic determinants. Our data indicate that the CD8
      coreceptor substantially enhances binding efficiency at suboptimal TCR/pMHCI
      affinities through effects on both association and dissociation rates.
      Interestingly, coreceptor requirements for efficient tetramer labeling of CTLs or
      for CTL activation by determinants displayed on the cell surface operated in
      different TCR/pMHCI affinity ranges. Wild-type and CD8-null pMHCI tetramers
      required monomeric affinities for cognate TCRs of KD < approximately 80 microM
      and approximately 35 microM, respectively, to label human CTLs at 37 degrees C.
      In contrast, activation by cellular pMHCI molecules was strictly dependent on CD8
      binding only for TCR/pMHCI interactions with KD values >200 microM. Altogether,
      our data provide information on the binding interplay between CD8 and the TCR and
      support a model of CTL activation in which the extent of coreceptor dependence is
      inversely correlated to TCR/pMHCI affinity. In addition, the results reported
      here define the range of TCR/pMHCI affinities required for the detection of
      antigen-specific CTLs by flow cytometry.

PMID- 17540779
TI  - Bcl10 mediates LPS-induced activation of NF-kappaB and IL-8 in human intestinal
      epithelial cells.
AB  - Lipopolysaccharide (LPS) is recognized as an inducer of the inflammatory response
      associated with gram-negative sepsis and systemic inflammatory response syndrome.
      LPS induction proceeds through Toll-like receptor (TLR) in immune cells and
      intestinal epithelial cells (IEC). This report presents the first identification
      of Bcl10 (B-cell CLL/lymphoma 10) as a mediator of the LPS-induced activation of
      IL-8 in human IEC. Bcl10 is a caspase-recruitment domain-containing protein,
      associated with constitutive activation of NF-kappaB in MALT (mucosa-associated
      lymphoid tissue) lymphomas. The normal human IEC line NCM460, normal primary
      human colonocytes, and ex vivo human colonic tissue were exposed to 10 ng/ml of
      LPS for 2-6 h. Effects on Bcl10, phospho-IkappaBalpha, NF-kappaB, and IL-8 were
      determined by Western blot, ELISA, immunohistochemistry, and confocal microscopy.
      Effects of Bcl10 silencing by small-interfering RNA (siRNA), TLR4 blocking
      antibody, TLR4 silencing by siRNA, and an IL-1 receptor-associated kinase (IRAK)
      1/4 inhibitor on LPS-induced activation were examined. Following Bcl10 silencing,
      LPS-induced increases in NF-kappaB, IkappaBalpha, and IL-8 were significantly
      reduced (P < 0.001). Increasing concentrations of LPS were associated with higher
      concentrations of Bcl10 protein when quantified by ELISA, and the association
      between LPS exposure and increased Bcl10 was also demonstrated by Western blot,
      immunohistochemistry, and confocal microscopy. Exposure to TLR4 antibody, TLR4
      siRNA, or an IRAK-1/4 inhibitor eliminated the LPS-induced increases in Bcl10, NF
      kappaB, and IL-8. Identification of Bcl10 as a mediator of LPS-induced activation
      of NF-kappaB and IL-8 in normal human IEC provides new insight into mechanisms of
      epithelial inflammation and new opportunities for therapeutic intervention.

PMID- 17540780
TI  - Involvement of Sp1 and Sp3 in differential regulation of human NHE3 promoter
      activity by sodium butyrate and IFN-gamma/TNF-alpha.
AB  - Previously, we reported that IFN-gamma and TNF-alpha downregulate the expression
      of the human Na(+)/H(+) exchanger (NHE)3 gene by modulating Sp1/Sp3 transcription
      factors in C2BBe1 cells. It is reported that butyrate inhibits IFN-gamma and TNF
      alpha signaling pathways. In this study, we have investigated the effect of
      sodium butyrate (NaB) and IFN-gamma/TNF-alpha on human NHE3 promoter activity. In
      transient transfection studies, NaB (5 mM) led to 10-fold stimulation of NHE3
      promoter activity after incubation for 24 h. With 5'-deletion analysis, the NaB
      responsive region was mapped to the NHE3 core promoter, bp -95 to + 5, which we
      had shown previously to confer responsiveness to IFN-gamma/TNF-alpha. The
      stimulatory effect of NaB on the NHE3 promoter was reduced by 60% in the presence
      of IFN-gamma/TNF-alpha. Mutually, the repressive effect of these cytokines was
      attenuated by NaB. Knockdown of Sp1 and Sp3 expression with small interfering RNA
      (siRNA) resulted in a significant resistance to NaB effects. NaB treatment showed
      no effect on Sp1 and Sp3 protein expression as assessed by Western blot analyses.
      Gel mobility shift assays with nuclear proteins from NaB-treated cells showed
      enhanced binding of Sp1 and Sp3 to the NHE3 promoter. The phosphatase inhibitor
      okadaic acid (200 nM) blocked the stimulatory effect of NaB on the NHE3 promoter.
      NaB effects on the NHE3 promoter were significantly attenuated by protein
      phosphatase (PP)1alpha- and PP2Aalpha-specific siRNA transfection. Our data
      suggest that the differential regulation of NHE3 gene expression by NaB and IFN
      gamma/TNF-alpha is mediated through alternative pathways that converge on
      Sp1/Sp3.

PMID- 17540781
TI  - A novel view of the transcriptome revealed from gene trapping in mouse embryonic
      stem cells.
AB  - Embryonic stem (ES) cells are pluripotent cell lines with the capacity of self
      renewal and the ability to differentiate into specific cell types. We performed
      the first genome-wide analysis of the mouse ES cell transcriptome using
      approximately 250,000 gene trap sequence tags deposited in public databases. We
      unveiled >8000 novel transcripts, mostly non-coding, and >1000 novel alternative
      and often tissue-specific exons of known genes. Experimental verification of the
      expression of these genes and exons by RT-PCR yielded a 70% validation rate. A
      novel non-coding transcript within the set studied showed a highly specific
      pattern of expression by in situ hybridization. Our analysis also shows that the
      genome presents gene trapping hotspots, which correspond to 383 known and 87
      novel genes. These "hypertrapped" genes show minimal overlap with previously
      published expression profiles of ES cells; however, we prove by real-time PCR
      that they are highly expressed in this cell type, thus potentially contributing
      to the phenotype of ES cells. Although gene trapping was initially devised as an
      insertional mutagenesis technique, our study demonstrates its impact on the
      discovery of a substantial and unprecedented portion of the transcriptome.

PMID- 17540782
TI  - Sleep apnoea screening in heart failure? Not until benefit is proven!

PMID- 17540783
TI  - Computed tomography and monitoring of emphysema.

PMID- 17540784
TI  - Rational monitoring of COPD: where do current clinical guidelines stand?

PMID- 17540785
TI  - Exacerbations of chronic obstructive pulmonary disease.
AB  - Exacerbations of chronic obstructive pulmonary disease are of major importance in
      terms of their prolonged detrimental effects on patients, the acceleration in
      disease progression and high healthcare costs. There is still debate about how
      exacerbations should be defined and graded, and their mechanisms are poorly
      understood. The major causal agents are either bacteria or viral infections, or a
      combination of the two. Noninfective causes include air pollution and pulmonary
      embolus but, in some patients, no cause is identified. Exacerbations represent an
      increase in the inflammation that is present in the stable state, with increased
      numbers of inflammatory cells (particularly neutrophils), cytokines, chemokines
      and proteases in the airways, and increased concentrations of certain cytokines
      and C-reactive protein in the blood. There are presently no reliable biomarkers
      with which to predict exacerbations. Exacerbations have a long-lasting adverse
      influence on health status. High doses of bronchodilators are the mainstay of
      treatment and systemic corticosteroids have some benefit. The routine use of
      antibiotics remains controversial but they are of benefit with exacerbations of a
      bacterial origin. Noninvasive ventilation is beneficial in preventing the need
      for intubation and its important complications but it is not certain whether its
      use in stable patients prevents exacerbations. Although important advances have
      been made, more effective treatments are needed in the future for prevention and
      treatment of exacerbations.

PMID- 17540786
TI  - Pharmacogenetics and asthma: false hope or new dawn?
AB  - Pharmacogenetic approaches provide the opportunity to improve prescribing for
      asthmatic patients in order to optimise efficacy and prevent side-effects.
      Currently, there are comprehensive data available on the extent of genetic
      variation in the human genome that will further this area of research. However,
      less is known about the functional consequences of many of the identified
      polymorphisms in genes whose products may predict drug efficacy. In addition,
      there is a shortage of well-designed, adequately powered clinical studies in this
      area. This series summarises the current state of knowledge and identifies areas
      for further research.

PMID- 17540787
TI  - T-cell co-stimulatory molecules: their role in allergic immune reactions.
AB  - The development of allergic diseases, such as allergic asthma, depends upon the
      initiation and maintenance of T-helper cell type-2-skewed allergen-specific
      immune reactions. Although it is clear that susceptibility to this process is
      under genetic and environmental control, the fine-tuning and regulation of the
      type-2 T-helper cell immune response is not yet fully understood. In this second
      article in the present series, current understanding regarding the involvement of
      T-cells and antigen-presenting cells is summarised, with emphasis on the
      interaction between these two types of immune regulatory cells by means of co
      stimulatory molecules.

PMID- 17540788
TI  - ERS guidelines on the assessment of cough.

PMID- 17540789
TI  - Hepatopulmonary syndrome following portopulmonary hypertension.
AB  - Portopulmonary hypertension (PPHTN) and hepatopulmonary syndrome (HPS) are
      distinct clinical entities that may accompany liver disease. While PPHTN and HPS
      have been infrequently described as occurring in the same patient, to the present
      authors' knowledge, the order of occurrence has always been the initial onset of
      HPS, with pulmonary hypertension developing either concurrently or subsequently.
      In some instances, liver transplantation has been undertaken for HPS, followed by
      resolution of the HPS and subsequent development of pulmonary hypertension. The
      current case study presents a patient with hepatitis C-related cirrhosis in whom
      PPTHN developed initially, followed 2 yrs later by the development of the HPS.
      The current authors speculate that progressive imbalance in favour of endogenous
      vasodilators over vasoconstrictive factors led to normalisation of the pulmonary
      artery pressures.

PMID- 17540790
TI  - Therapeutic bronchoscopy with immediate effect revisited: "tissue is the issue".

PMID- 17540791
TI  - Evidence for boosting Mycobacterium tuberculosis-specific IFN-gamma responses at
      6 weeks following tuberculin skin testing.

PMID- 17540792
TI  - Macrolides and bronchiolitis in infants.

PMID- 17540793
TI  - Antibiotics in RSV bronchiolitis: still no evidence of effect.

PMID- 17540795
TI  - Ensuring the future of family planning: the move toward excellence in
      contraceptive research.

PMID- 17540796
TI  - We are the champions (of women's health).

PMID- 17540797
TI  - Initiation of oral contraceptives using a quick start compared with a
      conventional start: a randomized controlled trial.
AB  - OBJECTIVE: To estimate whether young women taking the first pill on the day of
      prescription had higher continuation rates and lower pregnancy rates than women
      who waited until menses to start the oral contraceptive pill (OCP). METHODS: We
      recruited 1,716 women aged younger than 25 years seeking to initiate the oral
      contraceptive at three publicly funded family planning clinics, and randomly
      assigned them to conventional initiation of the pill (conventional start) or
      immediate, directly observed ingestion of the first pill (quick start) during the
      clinic visit. Women underwent follow-up interviews at 3 and 6 months. RESULTS:
      Sixty percent of participants discontinued the pill, and 8% became pregnant
      during follow-up. Women who took the first pill in the clinic were more likely to
      continue to the second OCP pack (odds ratio 1.5, 95% confidence interval 1.0
      2.1.); however, the Quick Start approach did not improve OCP continuation rates
      at 3 and 6 months. Those assigned to Quick Start were slightly less likely to
      become pregnant within 6 months from the time they started the pill (hazard ratio
      0.90, 95% confidence interval 0.64-1.25). Eighty-one percent of women rated the
      Quick Start approach as acceptable or preferable to waiting. Rates of serious
      adverse events were low and similar in the two groups. CONCLUSION: Protocols that
      require a woman to wait until the next menses to start hormonal contraceptives
      are an obstacle to contraceptive initiation. Directly observed, immediate
      initiation of the pill improves short-term continuation. CLINICAL TRIAL
      REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00068848

PMID- 17540798
TI  - Oral contraceptive tolerance: does the type of pill matter?
AB  - OBJECTIVE: To examine the frequencies of reported symptoms by oral contraceptive
      pill (OCP) composition among French women. METHODS: A population-based cohort of
      2,863 women studied between 2000 and 2004 was used to compare the frequency of
      reported symptoms (weight gain, nausea, breast tenderness, lower frequency of
      menstrual periods, breakthrough bleeding, painful and heavy periods, swollen
      legs) by type of OCPs (classified by estrogen dosage, progestin component, and
      sequence of administration). RESULTS: Results show little variation in the
      frequency of symptoms by type of OCPs, with the exception of progestin-only pills
      being associated with higher frequencies of breakthrough bleeding and lower
      frequencies of menstrual periods. We found no decrease in the reporting of
      symptoms with the reduction of estrogen dosage, nor with the use of third
      generation OCPs compared with second-generation OCPs. Likewise, we found little
      variation by sequence of administration of OCPs (monophasic versus triphasic).
      CONCLUSION: In the absence of sufficient evidence-based data to support the
      existence of differences in the tolerance profile of low-dose combined OCPs,
      future well-designed randomized trials are needed to guide providers in their
      choice of OCPs. However, research should also assess the effectiveness of
      counseling on the tolerance of OCPs, an intervention that may prove to be more
      rewarding than basing the choice of OCPs on their theoretical properties.

PMID- 17540799
TI  - Contraceptive effectiveness of immediate compared with delayed insertion of
      intrauterine devices after abortion: a decision analysis.
AB  - OBJECTIVE: To model rates of pregnancy and repeat abortion among women choosing
      intrauterine contraception after an abortion when the intrauterine device (IUD)
      is inserted immediately after the procedure or at a follow-up visit. METHODS: We
      created an evidence-based decision model of women desiring to avoid pregnancy for
      the 12 months after an abortion. Base case assumptions were pregnancy rates of
      0.5% with an IUD and 20% without an IUD, 1-year IUD continuation rate of 80%, an
      additional 5% risk of IUD expulsion with immediate insertion, and a 35% risk of
      not returning for a follow-up visit for IUD insertion. Sensitivity analyses and
      Monte Carlo simulation were performed. RESULTS: Immediate IUD insertion after
      abortion prevented 52 pregnancies over the following year for every 1,000 women
      modeled by using base case assumptions. Sensitivity analyses show the model to be
      most dependent on the rate of expulsion in the immediate-insertion group and the
      proportion not returning in the delayed-insertion group. Monte Carlo analysis
      showed that immediate insertion resulted in fewer pregnancies than delayed
      insertion in 91% of scenarios, with an absolute mean difference of 28 pregnancies
      per 1,000 women in the initial year after abortion. If 20% of U.S. women
      undergoing abortion opted for immediate insertion, an estimated 20,000 repeat
      abortions would be prevented in the first year. CONCLUSION: Women who have an IUD
      inserted immediately after an abortion are expected to have fewer pregnancies and
      repeat abortions than women scheduled for insertion of an IUD at a follow-up
      visit.

PMID- 17540800
TI  - Recurrent obstetric management mistakes identified by simulation.
AB  - OBJECTIVE: To develop a simulation-based curricular unit for labor and delivery
      teams involved in obstetric emergencies to detect and address common mistakes.
      METHODS: A simulation-based curricular unit for hands-on training of four
      obstetric emergency scenarios was developed using high-tech mannequins and low
      tech simulators. The scenarios were eclamptic seizure, postpartum hemorrhage,
      shoulder dystocia, and breech extraction. The obstetric teams consisted of at
      least one resident and two midwives. Checklists of actions expected from the
      teams were handed out to the course's tutors who observed the "event." All
      sessions were videotaped and then reviewed and analyzed by the trainees
      themselves, who were guided by two experienced tutors. We identified the most
      commonly occurring mistakes by summing up checklists and by watching the recorded
      sessions. RESULTS: Between February 2004 and April 2006, 60 residents in
      obstetrics and gynecology and 88 midwives underwent the simulation-based course.
      Forty-two labor and delivery teams completed all four sessions. The most common
      management errors were delay in transporting the bleeding patient to the
      operating room (82%), unfamiliarity with prostaglandin administration to reverse
      uterine atony (82%), poor cardiopulmonary resuscitation techniques (80%),
      inadequate documentation of shoulder dystocia (80%), delayed administration of
      blood products to reverse consumption coagulopathy (66%), and inappropriate
      avoidance of episiotomy in shoulder dystocia and breech extraction (32%).
      Eighteen trainees were invited for repeated sessions at least 6 months after the
      first training day, and their scores were significantly higher in the latter
      sessions (79.4+/-4.3 versus 70+/-5.3 for the second and first simulated eclampsia
      sessions). CONCLUSION: A curricular unit based on simulation of obstetric
      emergencies can identify pitfalls of management in labor and delivery rooms that
      need to be addressed.

PMID- 17540801
TI  - Late stillbirths and long-term mortality of mothers.
AB  - OBJECTIVE: To assess whether women who experienced stillbirths have an excess
      risk of long-term mortality. METHODS: We conducted a cohort study in the setting
      of the Jerusalem Perinatal Study, a population-based database of all births to
      West Jerusalem residents. Through data linkage with the Israeli Population
      Registry, we followed mothers who gave birth at least twice between 1964 and 1976
      and compared the survival of women who had at least one stillbirth (n=595) with
      that of women who had only live births (n=24,523), using Cox proportional hazards
      models. RESULTS: During the study period, 78 (13.1%) mothers with stillbirths
      died, compared with 1,518 (6.2%) women without stillbirth (crude hazard ratio
      2.08, 95% confidence interval [CI] 1.65-2.61). The mortality risk remained
      significantly increased after adjustments for sociodemographic variables,
      maternal diseases at pregnancy, placental abruption, and preeclampsia (hazard
      ratio 1.40, 95% CI 1.11-1.77). Stillbirth was associated with an increased risk
      of death from coronary heart disease (adjusted hazard ratio 2.00, 95% CI 1.02
      3.93), all circulatory (adjusted hazard ratio 1.70, 95% CI 1.02-2.84) and renal
      (adjusted hazard ratio 4.70, 95% CI 1.47-15.0) causes. Stratifying by country of
      origin, an increased risk was evident particularly among women of North African
      origin (all-cause mortality, adjusted hazard ratio 2.47, 95% CI 1.69-3.63).
      CONCLUSION: Stillbirth may be a risk marker for premature mortality among parous
      women.

PMID- 17540802
TI  - Association between maternal weight gain and birth weight.
AB  - OBJECTIVE: To investigate the association between maternal weight gain and birth
      weight less than 3,000 g and greater than or equal to 4,000 g in underweight
      (body mass index [BMI] less than 19.8 kg/m(2)), normal weight (BMI 19.8-26.0
      kg/m(2)), overweight (BMI 26.1-29.0 kg/m(2)), and obese (BMI greater than 29.0
      kg/m(2)) women, with emphasis on the use of the American Institute of Medicine
      (IOM) recommendations in Denmark. METHODS: We analyzed data from 2,248 women with
      singleton, term pregnancies. The relationship between weight gain and risk of
      birth weight less than 3,000 g and greater than or equal to 4,000 g was examined
      in the four BMI groups, and use of IOM recommendations was tested by logistic
      regression analyses. RESULTS: We found an inverse relationship between maternal
      weight gain and the proportion of infants with a birth weight less than 3,000 g.
      Birth weight greater than or equal to 4,000 g increased with an increasing weight
      gain in underweight and normal-weight women, but the association was less
      apparent in overweight and obese women. Underweight women seemed to benefit from
      gaining more weight than recommended by the IOM, because the odds ratio (OR) of
      birth weight less than 3,000 g was 0.3 (95% confidence interval [CI] 0.1-0.9) and
      the OR was 1.7 for birthweight greater than or equal to 4,000 g (95% CI 0.8-3.6).
      The normal-weight women had an increased risk of birth weight less than 3,000 g
      (OR 2.4, 95% CI 1.5-3.7) if weight gain was below the recommended range, and the
      OR of birth weight greater than or equal to 4,000 g was 1.9 (95% CI 1.5-2.5) when
      the women gained more than recommended. CONCLUSION: The IOM recommendations may
      provide a basis for Danish recommendations to pregnant women, although the upper
      recommended limit for underweight women may have to be increased.

PMID- 17540803
TI  - Circulating angiogenic factors in early pregnancy and the risk of preeclampsia,
      intrauterine growth restriction, spontaneous preterm birth, and stillbirth.
AB  - OBJECTIVE: To estimate the relationship between maternal serum levels of
      placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) in
      early pregnancy with the risk of subsequent adverse outcome. METHODS: A nested,
      case-control study was performed within a prospective cohort study of Down
      syndrome screening. Maternal serum levels of sFlt-1 and PlGF at 10-14 weeks of
      gestation were compared between 939 women with complicated pregnancies and 937
      controls. Associations were quantified as the odds ratio for a one decile
      increase in the corrected level of the analyte. RESULTS: Higher levels of sFlt-1
      were not associated with the risk of preeclampsia but were associated with a
      reduced risk of delivery of a small for gestational age infant (odds ratio [OR]
      0.92, 95% confidence interval [CI] 0.88-0.96), extreme (24-32 weeks) spontaneous
      preterm birth (OR 0.90, 95% CI 0.83-0.99), moderate (33-36 weeks) spontaneous
      preterm birth (OR 0.93, 95% CI 0.88-0.98), and stillbirth associated with
      abruption or growth restriction (OR 0.77, 95% CI 0.61-0.95). Higher levels of
      PlGF were associated with a reduced risk of preeclampsia (OR 0.95, 95% CI 0.90
      0.99) and delivery of a small for gestational age infant (OR 0.95, 95% CI 0.91
      0.99). Associations were minimally affected by adjustment for maternal
      characteristics. CONCLUSION: Higher early pregnancy levels of sFlt-1 and PlGF
      were associated with a decreased risk of adverse perinatal outcome.

PMID- 17540804
TI  - Risk of precancer and follow-up management strategies for women with human
      papillomavirus-negative atypical squamous cells of undetermined significance.
AB  - OBJECTIVE: To investigate the relative performances of follow-up cytology and
      carcinogenic human papillomavirus (HPV) DNA testing among carcinogenic HPV
      negative women with atypical squamous cells of undetermined significance (ASCUS),
      for detection of cervical precancer. METHODS: Twelve-month follow-up management
      strategies to detect cervical intraepithelial neoplasia grade 3 (CIN3) or worse
      using cytology or HPV testing or both were compared among women with HPV-negative
      ASCUS in the Atypical Squamous Cells of Undetermined Significance-Low-Grade
      Squamous Intraepithelial Lesion (ASCUS-LSIL) Triage Study. RESULTS: Overall only
      22 of 1,559 (1.4%) HPV-negative ASCUS women developed CIN grade 3 or worse during
      follow-up compared with 269 of 1,767 (15.2%) HPV-positive ASCUS women (P<.001).
      Because of the low risk of disease among HPV-negative ASCUS women, only 7 cases
      of CIN3 were diagnosed between 12 and 24 months of follow-up, limiting power to
      distinguish meaningful differences in sensitivity among 12-month testing
      strategies. The specificity of HPV testing (84%) was significantly higher than
      cytology using an ASCUS threshold (71%) (P<.001). Cotesting with cytology and HPV
      testing at 12 months resulted in even lower specificity (61%). Because cases were
      uncommon, the positive predictive value for subsequent CIN3 or worse was low for
      cytology (2.6%), Hybrid Capture 2 (3.8%), and cotesting with cytology and HPV
      testing (2.2%). The negative predictive value for all three management strategies
      was very high (99.70%, 99.82%, and 100.0% for HPV testing, cytology, or
      cotesting, respectively.) CONCLUSION: Women with HPV-negative ASCUS have very low
      absolute risk of subsequently detected CIN3 or worse in the subsequent 2 years,
      similar to women with a negative cytology in the absence of HPV testing. The
      results suggest that women with HPV-negative ASCUS should return to routine
      screening intervals which may be longer than 1 year depending on age and
      screening history. However, if increased surveillance is chosen, a single HPV
      test for carcinogenic types at 12 months has significantly higher specificity and
      lower referrals than cytology.

PMID- 17540805
TI  - Adherence to recommendations for follow-up to abnormal Pap tests.
AB  - OBJECTIVE: To evaluate whether timely adherence rates differ by race among women
      with abnormal Pap tests participating in a cost-free or reduced-cost program.
      METHODS: Eligible subjects included women aged 47-64 years who received a
      referral for follow-up care after an abnormal Pap test from 1999 to 2002 in South
      Carolina (n=330). Adherence was measured as days to receipt of follow-up care
      after an abnormal Pap test. Cox proportional hazards modeling was used to
      estimate risk factors associated with time to adherence within 60 and 365 days by
      race. RESULTS: African-American and non-Hispanic white women had similar
      adherence to follow-up. Among white women, those with high-grade lesions were
      less likely to adhere in a timely manner relative to those with low-grade lesions
      (hazard ratio 0.6, 95% confidence interval [CI] 0.4-1.0). For African-American
      women, rural residence (hazard ratio: 0.5, 95% CI 0.2-0.9) and history of
      abnormal Pap tests (hazard ratio 0.6, 95% CI 0.3-1.0) were associated with
      decreased adherence, whereas less education (hazard ratio 2.3, 95% CI 1.3-3.9)
      was associated with increased adherence. CONCLUSION: Adherence rates do not
      differ by race. However, risk factors for adherence within race are variable.
      Interventions tailored to the differential needs of racial and ethnic groups may
      prove effective toward increasing timely adherence rates. LEVEL OF EVIDENCE: II.

PMID- 17540806
TI  - Influence of the gynecologic oncologist on the survival of ovarian cancer
      patients.
AB  - OBJECTIVE: To estimate the influence of gynecologic oncologists on the treatment
      and outcome of patients with ovarian cancer. METHODS: Data were obtained from
      California Cancer Registry from 1994 to 1996. Kaplan-Meier and Cox proportional
      hazard methods were used for analyses. RESULTS: Of 1,491 patients, the median age
      was 65 years (range: 13-100). Only 34.1% received care by gynecologic oncologists
      (group A) while 65.9% were treated by others (group B). Women in group A were
      more affluent (P<.001), were more educated (P=.036), were classified as white
      collar employees (P=.128), and lived in urban regions (P<.001) compared with
      group B. Patients who saw gynecologic oncologists were more likely to have
      surgery as their initial treatment (91.9% versus 69.1%; P<.001), present with
      advanced (stage III-IV) cancers (78.2% versus 70.5%; P<.001), have more grade 3
      tumors (61.7% versus 39.9%; P=.048), and receive chemotherapy (90.0% versus
      70.1%; P<.001). Women in group B had a fourfold higher risk of having unstaged
      cancers (8.0% versus 2.1%; P<.001). The 5-year disease-specific survival of group
      A patients was 38.6% compared with 30.3% in group B (P<.001). On multivariable
      analysis, early stage, lower grade, and treatment by gynecologic oncologists were
      independent prognostic factors for improved survival. After adjusting for surgery
      and chemotherapy, there was no improvement in survival associated with care by
      gynecologic oncologists (hazard ratio=0.90, 95% confidence interval 0.78-1.03;
      P=.133). CONCLUSION: In this study of 1,491 women, those who were treated by
      gynecologic oncologists were more likely to undergo primary staging surgery and
      receive chemotherapy. Stage, grade of disease, and treatment by gynecologic
      oncologists were important prognosticators.

PMID- 17540807
TI  - Risk factors for cesarean delivery among Puerto Rican women.
AB  - OBJECTIVE: The rate of primary cesarean delivery in Puerto Rico in 2002 was 52%
      higher than in 1996 and 85% higher than among Puerto Rican women delivering on
      the U.S. mainland. Reasons for these differences were explored using birth
      certificate data. METHODS: Distributions of mothers' age, education, parity,
      level of prenatal care, pregnancy weight gain, medical risk factors, labor
      induction, labor or delivery complications, and infant birth weight among births
      in Puerto Rico in 2002 (n=40,489) were compared with births in Puerto Rico in
      1996 (n=51,357) and births to Puerto Rican women delivering on the mainland in
      2002 (n=47,800). Multivariable log-linear regression models were used to estimate
      relative risks for primary cesarean delivery by year, place of delivery, and
      selected risk factors. RESULTS: Risk for cesarean delivery was higher in Puerto
      Rico in 2002 than in both 1996 (relative risk 2.1, 95% confidence interval 2.0,
      2.3) and on the mainland in 2002 (relative risk 2.4, 95% confidence interval 2.2,
      2.6). This translates into one additional cesarean delivery in Puerto Rico in
      2002 for every 4.2 live births, controlled for examined risk factors. Higher
      rates of cesarean delivery in Puerto Rico in 2002 could not be explained by
      examined risk factors. CONCLUSION: Until further research reveals ways to safely
      reduce the rate of cesarean delivery in Puerto Rico, physicians, public health
      practitioners, and other stakeholders may want to focus their efforts on reducing
      rates among low-risk women and those with no labor complications. LEVEL OF
      EVIDENCE: II.

PMID- 17540808
TI  - Management of human immunodeficiency virus-infected pregnant women at Latin
      American and Caribbean sites.
AB  - OBJECTIVE: To describe the management of a population of human immunodeficiency
      virus (HIV)-infected pregnant women in Latin America and the Caribbean, and to
      assess factors associated with maternal viral load of 1,000 copies/mL or more and
      with infant HIV-1 infection. METHODS: Eligibility criteria were enrollment in the
      prospective cohort study as of March 2006; delivery of a liveborn, singleton
      infant; and completion of the 6-month postpartum or postnatal visit. RESULTS: Of
      955 women enrolled in Argentina, the Bahamas, Brazil, and Mexico, 770 mother
      infant pairs were eligible. At enrollment, most women were relatively healthy
      (87% asymptomatic, 59% with viral load less than 1,000 copies/mL, 62% with
      CD4(+)% of 25% or more). Most (99%) received antiretrovirals during pregnancy
      (56% prophylaxis, 44% treatment), and 38% delivered by cesarean before labor and
      before ruptured membranes. Only 18% of women had a viral load of 1,000 copies/mL
      or more after delivery (associated in adjusted analyses with receipt of
      antiretrovirals at conception, CD4(+)% [lower], viral load [higher], and country
      at enrollment, enrollment late in pregnancy, and inversely related to
      antiretroviral regimen [two nucleoside or nucleotide analogue reverse
      transcriptase inhibitors plus one nonnucleoside reverse transcriptase inhibitor]
      during pregnancy). None of the infants breastfed, and all received antiretroviral
      prophylaxis. Seven infants became infected (0.91%; 95% confidence interval 0.37
      1.86). Low birth weight infants and those whose mothers had a low CD4(+)% at
      hospital discharge after delivery and were not receiving antiretrovirals at
      enrollment were at higher risk of HIV infection. CONCLUSION: Only a minority of
      women had a viral load of 1,000 copies/mL or more around delivery, and mother-to
      child transmission of HIV occurred rarely (1%).

PMID- 17540809
TI  - Placental growth factor and soluble FMS-like tyrosine kinase-1 in early-onset and
      late-onset preeclampsia.
AB  - OBJECTIVE: To estimate whether alterations in plasma levels of the proangiogenic
      proteins placental growth factor (PlGF) and vascular endothelial growth factor-A
      (VEGF-A), and the antiangiogenic protein soluble fms-like tyrosine kinase-1
      (sFlt1) were more pronounced in early-onset than in late-onset preeclampsia.
      METHODS: A cross-sectional study was conducted to estimate the levels of sFlt1,
      PlGF, and VEGF-A in plasma in a control group of nonpregnant women, in an early
      control group of women at 24-32 weeks of gestation, in a late control group of
      women at 36-42 weeks of gestation, and in cases of women with early-onset (before
      32 weeks of gestation) and late-onset (after 35 weeks of gestation) preeclampsia.
      RESULTS: Women with early-onset preeclampsia had a 43 times higher median plasma
      sFlt1 level than early controls (P<.001). Women with late-onset preeclampsia had
      a three times higher median plasma sFlt1 level than late controls (P<.001). Women
      with early-onset preeclampsia had a 21 times lower median plasma PlGF level than
      early controls (P<.001). Women with late-onset preeclampsia had a five times
      lower median plasma PlGF level than late controls (P=.01). The median level of
      VEGF-A in plasma was less than 15 pg/mL in all groups of pregnant women.
      CONCLUSION: Both early- and late-onset preeclampsia are associated with altered
      plasma levels of sFlt1 and PlGF. The alterations are more pronounced in early
      onset rather than in late-onset disease.

PMID- 17540810
TI  - Tubal anastomosis by robotic compared with outpatient minilaparotomy.
AB  - OBJECTIVE: To compare tubal anastomosis by robotic system compared with
      outpatient minilaparotomy. METHODS: In this retrospective case-control study,
      women were identified by current procedural terminology code for tubal
      anastomosis. We included all cases of tubal anastomosis for reversal of a prior
      tubal ligation by either outpatient minilaparotomy or robotic system technique.
      Cases performed by laparoscopy without aid of the robot were excluded.
      Comparisons were based on Fisher's exact, chi(2), and Wilcoxon rank sum tests.
      RESULTS: There were 26 cases of tubal anastomosis performed with the robot and 41
      cases performed by outpatient minilaparotomy. The two groups were comparable in
      age, body mass index, and parity. Anesthesia time for the robotic technique
      (median with interquartile range) was 283 (267-290) minutes compared with 205
      (170-230) minutes with outpatient minilaparotomy (P<.001). Surgical times for the
      robot and minilaparotomy were 229 (205-252) minutes and 181 (154-202) minutes
      respectively (P=.001). Hospitalization times, pregnancy, and ectopic pregnancy
      rates were not significantly different. The robotic technique was more costly.
      The median difference in costs of the procedures was $1,446 (95% confidence
      interval $1,112-1,812) (P<.001). The time to return to work was significantly
      shorter in the robotic system group by approximately 1 week (P=.013). CONCLUSION:
      Robotic surgery for tubal anastomosis was successfully accomplished without
      conversion to laparotomy. The robotic technique for tubal anastomosis required
      significantly prolonged surgical and anesthesia times over outpatient
      minilaparotomy (P<or=.001). Costs were higher with the robotic technique. Return
      to normal activity was shorter with the robotic technique.

PMID- 17540811
TI  - Global endometrial ablation for menorrhagia in women with bleeding disorders.
AB  - OBJECTIVE: To evaluate the efficacy of global endometrial ablation in women with
      bleeding disorders who presented with menorrhagia. METHODS: A records-linkage
      system was used to construct a retrospective cohort of 41 women with bleeding
      disorders (coagulopathy) and a reference group of 111 randomly selected women
      without bleeding disorders from a pool of 943 women who underwent global
      endometrial ablation (with thermal balloon ablation technology or bipolar
      radiofrequency ablation technology) for menorrhagia at Mayo Clinic (Rochester,
      Minnesota) from January 1995 through December 2005. Demographic data, type of
      global endometrial ablation therapy and reablation, and hysterectomy data were
      extracted from the database. RESULTS: There was no significant difference in
      baseline age, parity, body mass index, uterine size, type of global endometrial
      ablation therapy, or duration of follow-up between the groups. Two women (5%) in
      the coagulopathy group had hysterectomy or reablation, compared with 8 (7%) in
      the reference group (Fisher exact test, P=.728). A Kaplan-Meier plot showed no
      difference in the time to treatment failure between the groups (log-rank test,
      P=.534). Procedural-related complications were generally minor and infrequent (9
      of 152 [6%]). Complications were equally distributed in the coagulopathy (4 of
      41) and reference groups (6 of 111) (Fisher exact test, P=.267). CONCLUSION:
      Global endometrial ablation is an effective treatment choice for women with
      coagulopathy presenting with menorrhagia.

PMID- 17540812
TI  - Cost-effectiveness analysis of strategies for the surgical management of grade 1
      endometrial adenocarcinoma.
AB  - OBJECTIVE: To estimate the costs and outcomes of various strategies used for the
      management of grade 1 endometrial cancer. METHODS: A cost-effectiveness analysis
      compared three strategies for the management of grade 1 endometrial cancer: 1)
      surgical staging in all patients (including hysterectomy and lymphadenectomy); 2)
      frozen section following hysterectomy with surgical staging based on the results
      of tumor grade and depth of myometrial invasion; and 3) hysterectomy without
      surgical staging (no staging). Surgical probabilities and recurrence rates were
      estimated from published data. Actual payer costs of surgery, radiation therapy,
      and chemotherapy were estimated for each strategy. Cost-effectiveness ratios were
      estimated for each strategy. Sensitivity analyses evaluated the costs of
      radiation and survival estimates used in the model. RESULTS: For the estimated
      10,000 women diagnosed annually with grade 1 endometrial cancer in the United
      States, the annual cost of surgical staging is $240.4 million, compared with
      $252.4 million for frozen section and $255.8 million for no staging. Five-year
      disease-free survival for surgical staging is 87.9%, compared with 87.3% for
      frozen section and 86.7% for no staging. This translates into a lower cost
      effectiveness ratio for surgical staging ($27,337) compared with frozen section
      ($28,913) or no staging ($29,513). Surgical staging yielded 64 additional disease
      free patients per 10,000 patients compared with frozen section and 126 additional
      disease-free patients compared with no staging. Use of adjuvant radiation therapy
      was the lowest in the surgical staging strategy (13%). CONCLUSION: Surgical
      staging of all patients with grade 1 endometrial cancer is the most cost
      effective strategy and decreases the use of radiation therapy without negatively
      impacting survival.

PMID- 17540813
TI  - Symptomatic pelvic organ prolapse: prevalence and risk factors in a population
      based, racially diverse cohort.
AB  - OBJECTIVE: To estimate the prevalence of and identify risk factors associated
      with symptomatic pelvic organ prolapse and level of distress in racially diverse
      women aged older than 40 years. METHODS: The Reproductive Risks for Incontinence
      Study at Kaiser is a population-based study of 2,001 randomly selected women.
      Symptomatic prolapse was determined by self-report of a feeling of bulge,
      pressure, or protrusion or a visible bulge from the vagina. Risk factors were
      assessed by self-report, interview, physical examination, and record review.
      Distress was assessed by self-report. Multivariable logistic regression analysis
      was used to identify independent risk factors. RESULTS: Symptomatic prolapse was
      reported by 118 (6%) women. Almost 50% of these women reported moderate or great
      distress, and 35% reported that the symptoms affected at least one physical,
      social or sexual activity. In multivariable analysis, the risk of prolapse was
      significantly increased in women with one (odds ratio [OR] 2.8, 95% confidence
      interval [CI] 1.1-7.2), two (OR 4.1, 95% CI 1.8-9.5), and three or more (OR 5.3,
      95% CI 2.3-12.3) vaginal deliveries compared with nulliparous women. Irritable
      bowel syndrome, constipation, and self-reported fair or poor health status were
      strongly associated with prolapse, with ORs of 2.8 (95% CI 1.7-4.6), 2.5 (95% CI
      1.7-3.7), and 2.3 (95% CI 1.1-4.9), respectively. African-American women were
      significantly less likely to report symptomatic prolapse compared with white
      women (OR 0.4, 95% CI 0.2-0.8). CONCLUSION: Symptomatic prolapse is less common
      among African-American women and more common among women with a prior vaginal
      delivery, poor health status, constipation, or irritable bowel syndrome. Nearly
      one half of women with symptomatic prolapse are substantially bothered by their
      symptoms.

PMID- 17540814
TI  - Age-specific levels for basal follicle-stimulating hormone assessment of ovarian
      function.
AB  - OBJECTIVE: Traditionally, the most important measurement in the assessment of
      ovarian function has been age-independent baseline follicle-stimulating hormone
      (FSH) levels. The objective of this study was to characterize the continuum of
      ovarian function based on age-specific categories of baseline FSH. METHODS: In a
      cross-sectional historical cohort study we evaluated records of 434 patients with
      baseline FSH levels of less than 12 milli international units/mL that underwent
      ovulation induction for in vitro fertilization (IVF) with long gonadotropin
      releasing hormone (GnRH) antagonist or GnRH agonist suppression and modal
      gonadotropin stimulation of 300 units of gonadotropins per day. In these patients
      with apparent normal ovarian function by current baseline FSH criteria and with
      routine ovarian stimulation, we assessed IVF cycle outcomes, including oocyte
      yields, based on age-specific baseline FSH levels, defined as levels less than or
      equal to the 95% confidence interval for each age group. RESULTS: Age-specific
      baseline FSH levels predicted the retrieval of fewer than or equal to four
      oocytes, with a positive predictive value of 19.5% and a negative predictive
      value of 88%. The Mantel-Haenszel common odds ratio for fewer than or equal to 4
      oocyte production in the presence of premature ovarian aging was 2.8 (95%
      confidence interval 1.52-5.17; P<.001). CONCLUSION: These results suggest that,
      within generally accepted normal baseline FSH values, women with baseline FSH
      above the 95% confidence limits for age produce fewer oocytes in response to
      normal ovulation induction protocols compared with other women their age.

PMID- 17540815
TI  - Patterns of and risk factors for recurrence in women with ovarian endometriomas.
AB  - OBJECTIVE: To identify risk factors for and the patterns of recurrence of
      endometrioma and of dysmenorrhea in women with ovarian endometrioma. METHODS: We
      evaluated 710 consecutive patients operated on for ovarian endometriomas who were
      followed up for an average of 22.4 months. Twenty factors were examined to assess
      their effect on risk of recurrence of endometrioma and of dysmenorrhea using
      survival analysis. Hazard rate also was estimated to examine recurrence patterns.
      RESULTS: For recurrence of endometrioma, the revised American Fertility Society
      (rAFS) score, younger age at surgery, and previous medical treatment of
      endometriosis were identified to be risk factors. For recurrence of dysmenorrhea,
      rAFS score was the only risk factor. For both recurrences, there was a constant
      hazard rate in the first 28-30 months after surgery, indicating that the
      recurrence in that period is completely random. After that period, the hazard
      rate increased dramatically. CONCLUSION: The total rAFS score, but not rAFS
      stage, is a risk factor for recurrence of both endometrioma and dysmenorrhea,
      indicating that the rAFS stage has little prognostic value. The existence of a
      completely random recurrence period may be a universal phenomenon, with its
      duration and the magnitude of recurrence risk determined by patient
      characteristics and quality of care. The second phase of much higher recurrence
      risk may reflect successful reseeding, reimplantation, and regrowth of ectopic
      endometrium. Therefore, the identification of risk factors as well as patterns of
      recurrence should shed better light on possible causes for recurrence, which is
      now poorly understood.

PMID- 17540816
TI  - Aromatase inhibitors in the treatment of severe endometriosis.
AB  - BACKGROUND: Endometriosis-associated chronic pelvic pain unresponsive to surgical
      menopause is a difficult clinical problem. CASE: A middle-aged woman presented
      with endometriosis and severe pelvic pain after hysterectomy and bilateral
      salpingo-oopherectomy. She was first treated with exemestane without improvement
      of symptoms. However, another aromatase inhibitor, letrozole, relieved her pain,
      and concomitant treatment with estrogen relieved hot flushes without pain
      reactivation. CONCLUSION: Letrozole was superior to exemestane in relieving the
      endometriosis-associated pain in this postmenopausal woman. This suggests that
      patients may respond variably to different aromatase inhibitors.

PMID- 17540817
TI  - Heterogeneity in anatomic outcome of sacrospinous ligament fixation for prolapse:
      a systematic review.
AB  - OBJECTIVE: To explore why failure rates vary so much between published reports of
      sacrospinous ligament fixation to correct pelvic organ prolapse and what the
      potential sources of heterogeneity may be. DATA SOURCES: MEDLINE was queried for
      studies between 1966 and 2005 that included the term "sacrospinous." METHODS OF
      STUDY SELECTION: One-hundred eighty-seven studies were reviewed. Studies were
      selected if they 1) involved a surgical procedure performed unilaterally with a
      posterior or apical vaginal incision and approach to the ligament; 2) reported
      objective outcomes with a classification system (Baden-Walker, pelvic organ
      prolapse quantification) over a defined follow-up period; and 3) were published
      in English, French, or German. Random effects meta-analyses were conducted for
      both objective and subjective measures of failure. TABULATION, INTEGRATION, AND
      RESULTS: Seventeen cohorts met the selection criteria, and the Baden-Walker
      vaginal profile or a close variation suitable for meta-analysis was used in 10 of
      them. Variability in failure rates was observed depending on site of and grade of
      vaginal support (P<.05). The anterior compartment was the most common site of
      failure for any given grade. This was most striking when the criterion for
      failure was grade 1 (40.1% anterior, 11.0% apical, 18.2% posterior) or grade 2
      prolapse (21.3% anterior, 7.2% apical, 6.3% posterior). Areas of vaginal support
      were more equally affected when the criterion for failure was grade 3 prolapse
      (3.7% anterior, 2.7% apical, 2.3% posterior). Among cohorts using grade 2
      prolapse as the criterion for objective failure, the pooled measure of failure to
      relieve symptoms was 10.3% (95% confidence interval 4.4-16.2%) and to provide
      patient satisfaction was 13.0% (95% confidence interval 7.4-18.6%). CONCLUSION:
      The variation in published failure rates after sacrospinous ligament fixation is,
      in part, accounted for by differences in how anatomical outcomes are evaluated
      and which compartment of vaginal support is being considered. Failure rates are
      highest in the anterior compartment.

PMID- 17540818
TI  - Reducing publication bias through trial registration.
AB  - Publication bias is the systematic, preferential publication of studies with
      statistically significant positive results over indeterminate studies
      (frequently, researchers inappropriately term these "negative" studies), or
      studies that show a statistically significant negative outcome. Over time, this
      practice distorts the medical literature, potentially compromising the validity
      of systematic reviews. Publication bias primarily stems from investigators, but
      data suppression can occur by pharmaceutical companies, universities, and
      regulatory agencies. Registration at inception of all clinical trials in a
      centralized, searchable database can reduce publication bias by enabling
      researchers to identify all studies related to a particular intervention. Prior
      attempts to encourage voluntary trial registration have been largely
      unsuccessful. Hence, the International Committee of Medical Journal Editors
      recently adopted a policy of mandatory clinical trial registration before
      consideration of manuscripts for publication. Trial registration and the
      development of comprehensive, computerized databases will promote transparency in
      research and help reduce publication bias.

PMID- 17540819
TI  - When a pregnancy seems like an ectopic... but isn't.

PMID- 17540820
TI  - S.O.S! I'm short of breath!
AB  - BACKGROUND: There are various causes of shortness of breath in a young, pregnant
      woman. The importance of entertaining a broad differential diagnosis is
      highlighted in this case. CASE: A young, pregnant African-American woman
      presented in her third trimester with acute onset of shortness of breath. A team
      approach by different medical specialties and systematic workup eventually helped
      us reach the diagnosis and provide optimal management. CONCLUSION: This case
      raises intriguing questions about diagnosis and management of a common symptom in
      a pregnant woman.

PMID- 17540821
TI  - A postoperative complication causing physician consternation.
AB  - BACKGROUND: Postoperative ileus and urinary retention are relatively common
      complications after obstetric and gynecologic procedures. This case highlights an
      unusual cause of these common postoperative patient reports. CASE: A 71-year-old
      woman underwent an uncomplicated total vaginal hysterectomy and pelvic
      reconstruction for stage III pelvic organ prolapse. She subsequently presented
      with and was hospitalized for labile blood pressures, ileus, urinary retention,
      and subjective sensory and motor complaints. The cause of the patient's reports
      was not clear until her disease became relatively severe. CONCLUSION: When a
      postoperative patient has multiple symptoms that do not respond to standard
      intervention, rare causes outside of one's specialty should be considered.

PMID- 17540822
TI  - College blues and hues.
AB  - BACKGROUND: Vulvar ulcerations are an entity that practicing gynecologists
      frequently encounter in daily practice. CASE: A 21-year-old nulliparous college
      student presented with a 3-day history of itching to the genital area with
      associated tenderness and sore bumps. She was initially treated for vulvovaginal
      candidiasis and instructed to return several days later for follow-up. Repeat
      examination revealed multiple coalescent and necrotic-appearing ulcerations
      confined to the labia minora, vagina, and posterior fourchette. All of the
      lesions eventually resolved. CONCLUSION: This case reminds us to broaden our
      differential diagnosis when considering causes of genital tract ulcerations in
      reproductive-aged females.

PMID- 17540823
TI  - Looks can be deceiving.
AB  - BACKGROUND: A thorough history, physical examination, and comprehensive work-up
      is important to differentiate the etiology of a cervical mass in unusual cases.
      CASE: A 36-year-old white female presented with heavy vaginal bleeding, pelvic
      pain, and an exophytic cervical mass extending to the anterior vaginal wall. She
      underwent cold knife cone with biopsies of the vagina. Pathology revealed
      dysgerminoma. Computed tomography of the abdomen and pelvis demonstrated pelvic
      lymphadenopathy, an enlarged uterus, and a 4 cm complex ovarian mass. The final
      pathology helped establish the true diagnosis. CONCLUSION: The accurate diagnosis
      of rare tumors requires a broad differential diagnosis and careful review of the
      pathologic findings and clinical scenario.

PMID- 17540825
TI  - Nuchal translucency and the risk of congenital heart disease.

PMID- 17540826
TI  - Menopausal hormone therapy: calculating risks and benefits.

PMID- 17540827
TI  - Menopausal hormone therapy: calculating risks and benefits.

PMID- 17540828
TI  - Effects of teamwork training on adverse outcomes and process of care in labor and
      delivery: a randomized controlled trial.

PMID- 17540829
TI  - Effects of teamwork training on adverse outcomes and process of care in labor and
      delivery: a randomized controlled trial.

PMID- 17540830
TI  - Human uterus retrieval from a multiorgan donor.

PMID- 17540835
TI  - ACCP evidence-based guideline development: a successful and transparent approach
      addressing conflict of interest, funding, and patient-centered recommendations.
AB  - Evidence-based clinical practice guidelines (EBGs) can provide an invaluable
      distillation of knowledge regarding best practices based on the available
      evidence. EBGs, providing accurate and useful guidance to best clinical
      practices, require a rigorous development process. The American College of Chest
      Physicians (ACCP) has developed a process that embodies transparency,
      thoroughness, and timeliness, and effective conflict-of-interest management, and
      it continues to evolve. This process employs a quantitative and rigorous grading
      of the strength of recommendations and of the quality of evidence that
      incorporates sensitivity to health-care resource utilization and patient values
      and preferences. A review of this process is provided to inform the ACCP
      membership and those wishing to embark on EBG development.

PMID- 17540836
TI  - Effects of prior very-heavy intensity exercise on indices of aerobic function and
      high-intensity exercise tolerance.
AB  - A recent bout of high-intensity exercise can alter the balance of aerobic and
      anaerobic energy provision during subsequent exercise above the lactate threshold
      (theta(L)). However, it remains uncertain whether such "priming" influences the
      tolerable duration of subsequent exercise through changes in the parameters of
      aerobic function [e.g., theta(L), maximum oxygen uptake (Vo(2max))] and/or the
      hyperbolic power-duration (P-t) relationship [critical power (CP) and the
      curvature constant (W')]. We therefore studied six men performing cycle ergometry
      to the limit of tolerance; gas exchange was measured breath-by-breath and
      arterialized capillary blood [lactate] was measured at designated intervals. On
      different days, each subject completed 1) an incremental test (15 W/min) for
      estimation of theta(L) and measurement of the functional gain
      (DeltaVo(2)/DeltaWR) and Vo(2peak) and 2) four constant-load tests at different
      work rates (WR) for estimation of CP, W', and Vo(2max). All tests were
      subsequently repeated with a preceding 6-min supra-CP priming bout and an
      intervening 2-min 20-W recovery. The hyperbolicity of the P-t relationship was
      retained postpriming, with no significant difference in CP (241 +/- 39 vs. 242 +/
      36 W, post- vs. prepriming), Vo(2max) (3.97 +/- 0.34 vs. 3.93 +/- 0.38 l/min),
      DeltaVo(2)/DeltaWR (10.7 +/- 0.3 vs. 11.1 +/- 0.4 ml.min(-1).W(-1)), or the
      fundamental Vo(2) time constant (25.6 +/- 3.5 vs. 28.3 +/- 5.4 s). W' (10.61 +/-
      2.07 vs. 16.13 +/- 2.33 kJ) and the tolerable duration of supra-CP exercise (-33
      +/- 11%) were each significantly reduced, despite a less-prominent Vo(2) slow
      component. These results suggest that, following supra-CP priming, there is
      either a reduced depletable energy resource or a residual fatigue-metabolite
      level that leads to the tolerable limit before this resource is fully depleted.

PMID- 17540837
TI  - The role of the large airways on smooth muscle contraction in asthma.

PMID- 17540838
TI  - Virtual conductance, real hypotension: what happens when we stand up too fast?

PMID- 17540839
TI  - Differential effects of static and cyclic stretching during elastase digestion on
      the mechanical properties of extracellular matrices.
AB  - Enzyme activity plays an essential role in many physiological processes and
      diseases such as pulmonary emphysema. While the lung is constantly exposed to
      cyclic stretching, the effects of stretch on the mechanical properties of the
      extracellular matrix (ECM) during digestion have not been determined. We measured
      the mechanical and failure properties of elastin-rich ECM sheets loaded with
      static or cyclic uniaxial stretch (40% peak strain) during elastase digestion.
      Quasistatic stress-strain measurements were taken during 30 min of digestion. The
      incremental stiffness of the sheets decreased exponentially with time during
      digestion. However, digestion in the presence of static stretch resulted in an
      accelerated stiffness decrease, with a time constant that was nearly 3 x smaller
      (7.1 min) than during digestion alone (18.4 min). These results were supported by
      simulations that used a nonlinear spring network model. The reduction in
      stiffness was larger during static than cyclic stretch, and the latter also
      depended on the frequency. Stretching at 20 cycles/min decreased stiffness less
      than stretching at 5 cycles/min, suggesting a rate-dependent coupling between
      mechanical forces and enzyme activity. Furthermore, pure digestion reduced the
      failure stress of the sheets from 88 +/- 21 kPa in control to 29 +/- 15 kPa (P <
      0.05), while static and cyclic stretch resulted in a failure stress of 7 +/- 5
      kPa (P < 0.05). We conclude that not only the presence but the dynamic nature of
      mechanical forces have a significant impact on enzyme activity, hence the
      deterioration of the functional properties of the ECM during exposure to enzymes.

PMID- 17540840
TI  - Endogenous platelet factor 4 stimulates activated protein C generation in vivo
      and improves survival after thrombin or lipopolysaccharide challenge.
AB  - Pharmacologic infusion of activated protein C (APC) improves survival in severe
      sepsis, and platelet factor 4 (PF4) accelerates APC generation in a primate
      thrombin-infusion model. We now tested whether endogenous platelet PF4 content
      affects APC generation. Mice completely deficient in PF4 (mPF4(-/-)) had impaired
      APC generation and survival after thrombin infusion, similar to the impairment
      seen in heterozygote protein C-deficient (PC(+/-)) mice. Transgenic mice
      overexpressing human PF4 (hPF4(+)) had increased plasma APC generation.
      Overexpression of platelet PF4 compensated for the defect seen in PC(+/-) mice.
      In both a thrombin and a lipopolysaccharide (LPS) survival model, hPF4(+) and
      PC(+/-)/hPF4(+) mice had improved survival. Further, infusion of hPF4(+)
      platelets improved survival of wild-type mice after an LPS challenge. These
      studies suggest that endogenous PF4 release may have biologic consequences for
      APC generation and survival in clinical sepsis. Infusions of PF4-rich platelets
      may be an effective strategy to improve outcome in this setting.

PMID- 17540841
TI  - Iron transferrin regulates hepcidin synthesis in primary hepatocyte culture
      through hemojuvelin and BMP2/4.
AB  - The peptide hormone hepcidin is the principal regulator of systemic iron
      homeostasis. We examined the pathway by which iron stimulates the production of
      hepcidin. In humans who ingested 65 mg of iron, the increase in transferrin
      saturation preceded by hours the increase in urinary hepcidin excretion.
      Increases in urinary hepcidin concentrations were proportional to the increment
      in transferrin saturation. Paradoxically, in previous studies in primary
      hepatocytes and cell lines, hepcidin response to iron or iron transferrin was not
      observed. We now report that freshly isolated murine primary hepatocytes
      responded to holotransferrin but not apotransferrin by increasing hepcidin mRNA.
      Hepcidin increase was not due to contamination of the transferrin preparations by
      endotoxin, a potent pathologic stimulus of hepcidin synthesis. Using this culture
      system, we showed that holotransferrin concentrations regulate hepcidin mRNA
      concentrations through a hemojuvelin/BMP2/4-dependent pathway. Although BMP9 is
      known to be expressed in the liver and potently increased the basal
      concentrations of hepcidin mRNA, it did not interact with hemojuvelin, and
      interference with its signaling pathway did not affect iron regulation. Fresh
      primary hepatocytes constitute a sufficient system for the regulation of hepcidin
      by physiologic iron stimuli and will greatly facilitate studies of major
      disorders of iron homeostasis.

PMID- 17540842
TI  - The cooperative activity between the carboxyl-terminal TSP1 repeats and the CUB
      domains of ADAMTS13 is crucial for recognition of von Willebrand factor under
      flow.
AB  - ADAMTS13 cleaves von Willebrand factor (VWF) between Tyr(1605) and Met(1606)
      residues at the central A2 subunit. The amino-terminus of ADAMTS13 protease
      appears to be sufficient to bind and cleave VWF under static and denatured
      condition. However, the role of the carboxyl-terminus of ADAMTS13 in substrate
      recognition remains controversial. Present study demonstrates that ADAMTS13
      cleaves VWF in a rotation speed- and protease concentration-dependent manner on a
      mini vortexer. Removal of the CUB domains (delCUB) or truncation after the spacer
      domain (MDTCS) significantly impairs its ability to cleave VWF under the same
      condition. ADAMTS13 and delCUB (but not MDTCS) bind VWF under flow with
      dissociation constants (K(D)) of about 50 nM and about 274 nM, respectively. The
      isolated CUB domains are neither sufficient to bind VWF detectably nor capable of
      inhibiting proteolytic cleavage of VWF by ADAMTS13 under flow. Addition of the
      TSP1 5-8 (T5-8CUB) or TSP1 2-8 repeats (T2-8CUB) to the CUB domains restores the
      binding affinity toward VWF and the inhibitory effect on cleavage of VWF by
      ADAMTS13 under flow. These data demonstrate directly and quantitatively that the
      cooperative activity between the middle carboxyl-terminal TSP1 repeats and the
      distal carboxyl-terminal CUB domains may be crucial for recognition and cleavage
      of VWF under flow.

PMID- 17540844
TI  - Revisions to the staging and classification of mycosis fungoides and Sezary
      syndrome: a proposal of the International Society for Cutaneous Lymphomas (ISCL)
      and the cutaneous lymphoma task force of the European Organization of Research
      and Treatment of Cancer (EORTC).
AB  - The ISCL/EORTC recommends revisions to the Mycosis Fungoides Cooperative Group
      classification and staging system for cutaneous T-cell lymphoma (CTCL). These
      revisions are made to incorporate advances related to tumor cell biology and
      diagnostic techniques as pertains to mycosis fungoides (MF) and Sezary syndrome
      (SS) since the 1979 publication of the original guidelines, to clarify certain
      variables that currently impede effective interinstitution and interinvestigator
      communication and/or the development of standardized clinical trials in MF and
      SS, and to provide a platform for tracking other variables of potential
      prognostic significance. Moreover, given the difference in prognosis and clinical
      characteristics of the non-MF/non-SS subtypes of cutaneous lymphoma, this
      revision pertains specifically to MF and SS. The evidence supporting the
      revisions is discussed as well as recommendations for evaluation and staging
      procedures based on these revisions.

PMID- 17540843
TI  - MEK1/2 inhibitors potentiate UCN-01 lethality in human multiple myeloma cells
      through a Bim-dependent mechanism.
AB  - The role of Bim in synergistic interactions between UCN-01 and MEK1/2 inhibitors
      in human multiple myeloma cells was investigated. Exposure of U266 or RPMI8226
      cells to UCN-01 resulted in ERK1/2 activation-associated Bim(EL)
      phosphorylation/down-regulation, events abrogated by MEK1/2 inhibitors. Enforced
      activation of ERK1/2 by transfection with constitutively active MEK1 diminished
      the capacity of PD98059 but not PD184352 to block UCN-01-mediated Bim(EL)
      phosphorylation and to potentiate apoptosis. Cotreatment with MEK1/2 inhibitors
      increased the association of Bim(EL) with both Bcl-2 and Bcl-x(L) in UCN-01
      treated cells, leading to Bax/Bak conformational change and Bax mitochondrial
      translocation. Down-regulation of Bim(EL) by shRNA substantially diminished UCN
      01/MEK inhibitor-mediated Bax/Bak activation and apoptosis. Furthermore,
      transfection of cells with S65A Bim, a mutant resistant to UCN-01-mediated
      phosphorylation, significantly sensitized cells to UCN-01 lethality. Conversely,
      ectopic expression of either Bcl-2 or Bcl-x(L) did not alter UCN-01/MEK1/2
      inhibitor-mediated modifications in Bim(EL) phosphorylation but largely prevented
      cell death. Finally, IL-6 or IGF-1 failed to prevent MEK1/2 inhibitors from
      blocking UCN-01-induced Bim(EL) phosphorylation/degradation or cell death.
      Collectively, these findings argue that UCN-01-mediated ERK1/2 activation leads
      to Bim(EL) phosphorylation/inactivation, resulting in cytoprotection, and that
      interference with these events by MEK1/2 inhibitors plays a critical role in
      synergistic induction of apoptosis by these agents.

PMID- 17540845
TI  - Critical role of FLT3 ligand in IL-7 receptor independent T lymphopoiesis and
      regulation of lymphoid-primed multipotent progenitors.
AB  - The molecular pathways regulating lymphoid priming, fate, and development of
      multipotent bone marrow (BM) stem/progenitor cells that continuously replace
      thymic progenitors remain largely unknown. Herein, we show that fms-like tyrosine
      kinase 3 (Flt3) ligand (Fl)-deficient mice have distinct reductions in the
      earliest thymic progenitors in fetal, postnatal, and adult thymus. A critical
      role of FL in thymopoiesis was particularly evident in the absence of interleukin
      7 receptor alpha (IL-7Ralpha) signaling. Fl-/-Il-7r-/- mice have extensive
      reductions in fetal and postnatal thymic progenitors that result in a loss of
      active thymopoiesis in adult mice, demonstrating an indispensable role of FL in
      IL-7Ralpha-independent fetal and adult T lymphopoiesis. Moreover, we establish a
      unique and critical role of FL, distinct from that of IL-7Ralpha, in regulation
      of the earliest lineage-negative (Lin(-)) Lin(-)SCA1+KIT+ (LSK) FLT3(hi) lymphoid
      primed multipotent progenitors in BM, demonstrating a key role of FLT3 signaling
      in regulating the very earliest stages of lymphoid progenitors.

PMID- 17540846
TI  - Negative regulation of the SH2-homology containing protein-tyrosine phosphatase-1
      (SHP-1) P2 promoter by the HTLV-1 Tax oncoprotein.
AB  - Expression of SH(2)-homology-containing protein-tyrosine phosphatase-1 (SHP-1), a
      candidate tumor suppressor, is repressed in human T-cell leukemia virus type-1
      (HTLV-1)-transformed lymphocyte cell lines, adult T-cell leukemia (ATL) cells,
      and in other hematologic malignancies. However, the mechanisms underlying
      regulation and repression of SHP-1 remain unclear. Herein, we cloned the putative
      full-length, hematopoietic cell-specific SHP-1 P2 promoter and identified the
      "core" promoter regions. HTLV-1 Tax profoundly represses P2 promoter activity and
      histone deacetylase-1 (HDAC1) potentiates such inhibition. NF-kappaB was
      implicated as both a rate-limiting factor for basal P2 promoter activity and
      important for Tax-induced promoter silencing (TIPS). Chromatin
      immunoprecipitation studies demonstrated that NF-kappaB dissociates from the SHP
      1 P2 promoter following the binding of Tax and HDAC1. This is in agreement with
      coimmunoprecipitation studies where NF-kappaB competed with HDAC1 for association
      with Tax protein. We propose that in TIPS, Tax recruits HDAC1 to the SHP-1 P2
      promoter and forms an inhibitory complex that results in deacetylation and
      dissociation of NF-kappaB from the promoter and attenuation of SHP-1 expression.
      TIPS provides a possible first step toward HTLV-1 leukemogenesis through its down
      modulation of this key immediate early negative regulator of IL-2 signaling.

PMID- 17540847
TI  - Chemokine-idiotype fusion DNA vaccines are potentiated by bivalency and
      xenogeneic sequences.
AB  - V regions of monoclonal Ig express an exquisite B-cell tumor-specific antigen
      called idiotype (Id). Id is a weak antigen and it is important to improve
      immunogenicity of Id vaccines. Chemokine receptors are expressed on antigen
      presenting cells (APCs) and are promising targets for Id vaccines. Here we
      compare monomeric and dimeric forms of MIP-1alpha and RANTES that target Id to
      APCs in a mouse B lymphoma (A20) and a multiple myeloma model (MOPC315). MIP
      1alpha was more potent than RANTES. The dimeric proteins were more potent than
      monomeric equivalents in short-term assays. When delivered in vivo by
      intramuscular injection of plasmids followed by electroporation, dimeric proteins
      efficiently primed APCs in draining lymph nodes for activation and proliferation
      of Id-specific CD4(+) T cells. Good anti-Id antibody responses were obtained, and
      mice immunized only once were 60% to 80% protected in both tumor models. CD8(+) T
      cells contributed to the protection. Antibody responses and tumor protection were
      reduced when the human Ig hinge = C(H)3 dimerization motif was replaced with
      syngeneic mouse counterparts, indicating that tumor-protective responses were
      dependent on xenogeneic sequences. The results suggest that bivalency and foreign
      sequences combine to increase the efficiency of chemokine-Id DNA vaccines.

PMID- 17540848
TI  - Predictors and treatment response with cardiac resynchronization therapy in
      patients with heart failure characterized by dyssynchrony: a pre-defined analysis
      from the CARE-HF trial.
AB  - AIMS: The cardiac resynchronization therapy in heart failure trial (CARE-HF)
      demonstrated that cardiac resynchronization therapy (CRT) reduces morbidity and
      mortality in patients with heart failure and cardiac dyssynchrony. The aim of
      this study was to develop a prognostic model to evaluate the relationship between
      prospectively defined patient characteristics and treatment on the trial primary
      outcome of death from any cause or unplanned hospitalization for a major
      cardiovascular event. METHODS AND RESULTS: A total of 813 patients were enrolled
      in the CARE-HF study and were followed for a mean of 29.4 months. A Cox
      Proportional Hazards Model was fitted to identify predictors of the primary
      outcome and any predictors that modified the effect of CRT. Ischaemic aetiology,
      more severe mitral regurgitation and increased N-terminal pro-brain natriuretic
      peptide, were associated with an increased risk of death or unplanned
      cardiovascular hospitalization irrespective of cardiac resynchronization [Hazard
      ratio (HR) 1.89, 95% CI 1.45-2.46, HR 1.71, 95% CI 1.38-2.12 and HR 1.31, 95% CI
      1.17-1.47, respectively] and increasing systolic blood pressure with a decreasing
      risk of an event (HR 0.99, 95% CI 0.98-1.00). The benefits of cardiac
      resynchronization were modified by systolic blood pressure and interventricular
      mechanical delay (IVMD). Patients with increasing systolic blood pressure appear
      to receive reduced benefit from CRT (HR 1.02, 95% CI 1.00-1.03), whereas those
      patients with more severe IVMD appear to benefit more from treatment (HR 0.99,
      95% CI 0.98-1.00). CONCLUSION: Patients with echocardiographic evidence of more
      severe cardiac dyssynchrony and low systolic blood pressure obtain greater
      benefit from CRT, although benefits were substantial across the range of subjects
      included in the trial.

PMID- 17540849
TI  - Effect of the polymer-based, paclitaxel-eluting TAXUS Express stent on vascular
      tissue responses: a volumetric intravascular ultrasound integrated analysis from
      the TAXUS IV, V, and VI trials.
AB  - AIMS: The TAXUS Express stent has been shown to reduce angiographic restenosis,
      repeat revascularizations, and neointimal hyperplasia when compared with bare
      metal stent (BMS) control (TAXUS IV, V, and VI) in individual TAXUS trials. Since
      intravascular ultrasound (IVUS) methodology and core laboratory were consistent
      among all three TAXUS trials, an integrated analysis of 956 patients across all
      IVUS cohorts can be performed providing superior power. METHODS AND RESULTS: In
      the TAXUS randomized trials, patients received an Express BMS or paclitaxel
      eluting TAXUS Express stent. Volumetric analysis was performed on a selected
      subgroup at implantation and 9 months. Compared with BMS control, TAXUS increased
      9-month lumen volumes (144 +/- 79 vs. 179 +/- 95 mm(3); P < 0.0001) due to
      reduced neointimal volume (66 +/- 49 vs. 27 +/- 30 mm(3); P < 0.0001). This
      corresponded to a 61% decrease in net lumen volume obstruction (31 +/- 15 vs. 12
      +/- 12 mm(3); P < 0.0001). Lumen loss was similar between groups for the proximal
      5 mm outside the stent but was reduced in TAXUS at the distal edge (P = 0.0056).
      Neointimal hyperplasia was significantly reduced in the double-strut region of
      overlapping TAXUS vs. BMS control and in high-risk patients with diabetes, long
      lesions, multiple stents, and multiple overlapping stents. Late-acquired
      incomplete stent apposition (ISA) was more common with moderate-release TAXUS
      stents. Importantly, there were no major adverse cardiac events or stent
      thromboses in any late-acquired ISA patient through 2 years. Univariate and
      multivariable analyses revealed that longer lesion length and previous myocardial
      infarction are risk factors for late-acquired ISA. CONCLUSION: Integrated
      analysis of the TAXUS trials shows that the paclitaxel-eluting TAXUS Express
      stent effectively inhibits in-stent neointimal proliferation, even in high-risk
      and overlapping stent patients.

PMID- 17540850
TI  - Intravascular ultrasound assessment of remodelling and reference segment plaque
      burden in type-2 diabetic patients.
AB  - AIMS: Intravascular ultrasound (IVUS) assesses arterial remodelling by comparing
      the lesion external elastic membrane (EEM) with the reference segments; however,
      reference segments are rarely disease-free. The aim was to assess lesion and
      reference segment remodelling and plaque burden in patients with type-2 diabetes
      mellitus. METHODS AND RESULTS: We used pre-intervention IVUS to study 62 de novo
      lesions in 43 patients with type-2 diabetes mellitus. The lesion site was the
      image slice with the smallest lumen cross-sectional area (CSA). The proximal and
      distal reference segments were the most normal-looking segments within 5 mm
      proximal and distal to the lesion. Plaque burden was measured as plaque CSA/EEM
      CSA. The remodelling index was defined as lesion EEM CSA/mean reference EEM CSA.
      Reference segment plaque burden measured 0.54 +/- 0.09. The majority of lesions
      (83.9%) had negative remodelling (lesion EEM < reference). Similarly, the slope
      of the regression line relating EEM to plaque CSA within the lesion was less than
      the reference substantiating negative remodelling. The reference segment plaque
      burden correlated inversely with the difference between IVUS lumen and
      quantitative coronary angiographic artery size [slope = -0.12 (95% CI -0.17 to 
      0.07); P < 0.001] in all patients with type-2 diabetes mellitus. CONCLUSION:
      Lesions in type-2 diabetic patients are different from previous reports in non
      diabetics. Lesions in type-2 diabetics are characterized by a large reference
      segment plaque burden and negative lesion site remodelling. These IVUS findings
      may explain the angiographic appearance of small arteries in diabetic patients.

PMID- 17540851
TI  - Non-invasive coronary computed tomographic angiography for patients with
      suspected coronary artery disease: the Coronary Angiography by Computed
      Tomography with the Use of a Submillimeter resolution (CACTUS) trial.
AB  - BACKGROUND: Non-invasive coronary angiography by multislice spiral computed
      tomography (MSCT) is a promising method for the diagnosis of coronary artery
      disease (CAD). However, the clinical role of this method has not been established
      for specific patient cohorts. Therefore, the objective of the current
      prospective, blinded study was to investigate the diagnostic value of coronary
      MSCT angiography in patients with an intermediate pre-test probability for having
      CAD when compared with invasive angiography. METHODS AND RESULTS: A total of 243
      patients with an intermediate pre-test probability for having CAD were asked to
      undergo coronary 16- or 64-slice CT angiography before planned invasive
      angiography from 12 September 2003 to 13 July 2005. The primary end point was
      defined as the diagnostic accuracy in the detection of significant coronary
      stenosis (> or =50% lumen diameter reduction) on a per-patient and an 'intention
      to-diagnose'-based analysis. Secondary end points comprised per-artery and per
      segment-based analyses as well as the comparison of diagnostic accuracy of 16-
      vs. 64-slice MSCT angiography. Of 243 enrolled patients, 129 and 114 patients
      were studied by 16- and 64-slice CT angiography, respectively. The overall
      sensitivity, negative predictive value, and specificity for CAD detection by MSCT
      were 99% (95% CI, 94-99%), 99% (95% CI, 94-99%), and 75% (95% CI, 67-82%),
      respectively. On a per-segment basis, the use of 64-slice CT was associated with
      significantly less inconclusive segments (7.4 vs. 11.3%, P < 0.01), resulting in
      a trend to an improved specificity (92 vs. 88%, P = 0.09). CONCLUSION: In
      patients with an intermediate pre-test probability for having CAD this large,
      prospective trial demonstrates that non-invasive coronary CT angiography is a
      very sensitive method for CAD detection. Furthermore, this method allows ruling
      out CAD very reliably and safely. Finally, 64-slice CT appears to be superior for
      CAD detection when compared with 16-slice CT.

PMID- 17540852
TI  - Extending Jak2V617F and MplW515 mutation analysis to single hematopoietic
      colonies and B and T lymphocytes.
AB  - JAK2V617F and MPLW515L/K are myeloproliferative disorder (MPD)-associated
      mutations. We genotyped 552 individual hematopoietic colonies obtained by CD34+
      cell culture from 16 affected patients (13 JAK2V617F and 3 MPLW515L/K) to
      determine (a) the proportion of colonies harboring a particular mutation in the
      presence or absence of cytokines, (b) the lineage distribution of endogenous
      colonies for each mutation, and (c) the differences (if any) in the pattern of
      mutation among the various MPDs, as established by genotyping of individual
      colonies. Genotyping analysis revealed cohabitation of mutation-negative and
      mutation-positive endogenous colonies in polycythemia vera as well as other MPDs.
      Culture of progenitor cells harboring MPLW515L/K yielded virtually no endogenous
      erythroid colonies in contrast to JAK2V617F-harboring progenitor cells. The
      mutation pattern (i.e., relative distribution of homozygous, heterozygous, or
      wild-type colonies) was not a distinguishing feature among the MPDs, and MPLW515
      mutations were detected in B and/or T lymphocytes in all three patients tested.
      These observations suggest that clonal myelopoiesis antedates acquisition of
      JAK2V617F or MPLW515L/K mutations and that the latter is acquired in a lympho
      myeloid progenitor cell.

PMID- 17540853
TI  - Differentiation in vivo of cardiac committed human embryonic stem cells in
      postmyocardial infarcted rats.
AB  - Human embryonic stem (HES) cells can give rise to cardiomyocytes in vitro.
      However, whether undifferentiated HES cells also feature a myocardial
      regenerative capacity after in vivo engraftment has not been established yet. We
      compared two HES cell lines (HUES-1 and I6) that were specified toward a cardiac
      lineage by exposure to bone morphogenetic protein-2 (BMP2) and SU5402, a
      fibroblast growth factor receptor inhibitor. Real-time polymerase chain reaction
      (PCR) revealed that the cardiogenic inductive factor turned on expression of
      mesodermal and cardiac genes (Tbx6, Isl1, FoxH1, Nkx2.5, Mef2c, and alpha-actin).
      Thirty immunosuppressed rats underwent coronary artery ligation and, 2 weeks
      later, were randomized and received in-scar injections of either culture medium
      (controls) or BMP2 (+/-SU5402)-treated HES cells. After 2 months, human cells
      were detected by anti-human lamin immunostaining, and their cardiomyocytic
      differentiation was evidenced by their expression of cardiac markers by reverse
      transcription-PCR and immunofluorescence using an anti-beta myosin antibody. No
      teratoma was observed in hearts or any other organ of the body. The ability of
      cardiac-specified HES cells to differentiate along the cardiomyogenic pathway
      following transplantation into infarcted myocardium raises the hope that these
      cells might become effective candidates for myocardial regeneration.

PMID- 17540854
TI  - Tissue engineering with chondrogenically differentiated human embryonic stem
      cells.
AB  - This study describes the development and application of a novel strategy to
      tissue engineer musculoskeletal cartilages with human embryonic stem cells
      (hESCs). This work expands the presently limited understanding of how to
      chondrogenically differentiate hESCs through the use of chondrogenic medium alone
      (CM) or CM with two growth factor regimens: transforming growth factor (TGF)
      beta3 followed by TGF-beta1 plus insulin-like growth factor (IGF)-I or TGF-beta3
      followed by bone morphogenic protein (BMP)-2. It also extends the use of the
      resulting chondrogenically differentiated cells for cartilage tissue engineering
      through a scaffoldless approach called self-assembly, which was conducted in two
      modes: with (a) embryoid bodies (EBs) or (b) a suspension of cells enzymatically
      dissociated from the EBs. Cells from two of the differentiation conditions (CM
      alone and TGF-beta3 followed by BMP-2) produced fibrocartilage-like constructs
      with high collagen I content, low collagen II content, relatively high total
      collagen content (up to 24% by dry weight), low sulfated glycosaminoglycan
      content (approximately 4% by dry weight), and tensile properties on the order of
      megapascals. In contrast, hESCs treated with TGF-beta3 followed by TGF-beta1 +
      IGF-I produced constructs with no collagen I. Results demonstrated significant
      differences among the differentiation conditions in terms of other biochemical
      and biomechanical properties of the self-assembled constructs, suggesting that
      distinct growth factor regimens differentially modulate the potential of the
      cells to produce cartilage. Furthermore, this work shows that self-assembly of
      cells obtained by enzymatic dissociation of EBs is superior to self-assembly of
      EBs. Overall, the results of this study raise the possibility of manipulating the
      characteristics of hESC-generated tissue toward specific musculoskeletal
      cartilage applications.

PMID- 17540855
TI  - Stem cell therapy for human liver cirrhosis: a cautious analysis of the results.
AB  - End-stage liver disease, and in particular human liver cirrhosis, represents a
      worldwide health problem. Currently, liver transplant is the only effective
      treatment, but it is affected by many problems, including relative lack of
      donors, operative damage, risk of rejection, and high costs. Stem cell therapy is
      very attractive in this setting because it has the potential to help tissue
      regeneration while providing minimally invasive procedures and few complications.
      Only a few clinical studies on the administration of bone marrow-derived stem
      cells to cirrhotic patients have been published up to now. Although preliminary
      results seem to be encouraging, the number of treated patients is too small and
      the study design not completely appropriate to demonstrate safety and efficacy of
      stem cell therapy in liver cirrhosis. Well designed, randomized, controlled
      studies are needed to confirm preliminary results and eventually clear doubts.

PMID- 17540856
TI  - New GABAergic interneurons supported by myelin-specific T cells are formed in
      intact adult spinal cord.
AB  - Neural stem/progenitor cells are known to exist in the intact spinal cord, but
      the presence of newly formed neurons during adulthood has not been documented
      there to date. Here, we report the appearance of newly formed neurons under
      normal physiological conditions. These neurons are immature, express a GABAergic
      phenotype, and are primarily located in the dorsal part of the spinal cord. This
      localization appeared to be mediated by stromal-derived factor-1/CXC-chemokine
      receptor-4 signaling in the dorsal region. The extent of spinal cord neurogenesis
      was found to be greatly influenced by immune system integrity and in particular
      by myelin-specific T cells. These observations provide evidence for in vivo
      spinal cord neurogenesis under nonpathological conditions and introduce novel
      mechanisms regulating adult spinal cord plasticity.

PMID- 17540858
TI  - Pharmacological properties of 3-amino-5,6,7,8-tetrahydro-2-[4-[4-(quinolin-2
      yl)piperazin-1-yl]butyl]quinazolin-4(3H)-one (TZB-30878), a novel therapeutic
      agent for diarrhea-predominant irritable bowel syndrome (IBS) and its effects on
      an experimental IBS model.
AB  - 3-Amino-5,6,7,8-tetrahydro-2-[4-[4-(quinolin-2-yl)piperazin-1-yl]butyl]quinazolin
      4(3H)-one (TZB-30878) is a novel compound with both 5-hydroxytryptamine (5
      HT)(1A) agonism and 5-HT(3) antagonism effects. We hypothesized that TZB-30878
      might have benefits from these dual effects as a medication for diarrhea
      predominant irritable bowel syndrome (d-IBS), and these studies were designed to
      confirm the pharmacological properties of TZB-30878 and its efficacy in an IBS
      like animal model. The binding assays demonstrated that [(3)H]TZB-30878
      selectively binds to human 5-HT(1A) and 5-HT(3) receptors, with K(d) values of
      0.68 +/- 0.03 and 8.90 +/- 1.73 nM, respectively. Systemic administration of TZB
      30878 inhibited 5-HT-induced bradycardia in a dose-dependent manner in rats. In
      behavioral assays TZB-30878 produced signs of 5-HT syndrome in rats. These
      results suggest that TZB-30878 has dual effects as a 5-HT(1A) receptor agonist
      and a 5-HT(3) receptor antagonist. Finally, we evaluated the effects of TZB-30878
      on wrap restraint stress-induced defecation in an IBS-like model in rats. TZB
      30878 (1-10 mg/kg p.o.) normalized stress-induced defecation in a dose-dependent
      manner, whereas the 5-HT(1A) agonist tandospirone (30 and 100 mg/kg p.o.) and the
      5-HT(3) antagonist alosetron (1-10 mg/kg p.o.) did not show such effects.
      Furthermore, this efficacy of TZB-30878 was partly antagonized by a 5-HT(1A)
      antagonist, [O-methyl-3H]-N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2
      pyridinyl)cyclohexanecarboxamide trihydrochloride (WAY-100635). These results
      suggest that 5-HT(1A) receptor agonism and 5-HT(3) receptor antagonism contribute
      to the efficacy of TZB-30878 in the IBS-like model. The efficacy of TZB-30878
      supports the concept that the presence of both actions, namely 5-HT(1A) receptor
      agonism and 5-HT(3) receptor antagonism, could be an important mechanism in the
      treatment of d-IBS.

PMID- 17540857
TI  - Angiogenic effects of human multipotent stromal cell conditioned medium activate
      the PI3K-Akt pathway in hypoxic endothelial cells to inhibit apoptosis, increase
      survival, and stimulate angiogenesis.
AB  - Recent reports indicated that vascular remodeling and angiogenesis are promoted
      by conditioned medium from the cells referred to as multipotent stromal cells
      (MSCs). However, the molecular events triggered by MSC-conditioned medium (CdM)
      were not defined. We examined the effects of CdM from human MSCs on cultures of
      primary human aortic endothelial cells (HAECs). The CdM inhibited hypoxia-induced
      apoptosis and cell death of HAECs. It also promoted tube formation by HAECs in an
      assay in vitro. Conditioned medium from multipotent stromal cells incubated under
      hypoxic conditions in serum-free endothelial basal medium for 2 days (CdM(Hyp))
      from hypoxic culture of MSCs was more effective than conditioned medium from MSCs
      incubated under normoxic conditions in serum-free endothelial basal medium for 2
      days from normoxic cultures of MSCs, an observation in part explained by its
      higher content of antiapoptotic and angiogenic factors, such as interleukin (IL)
      6, vascular endothelial growth factor (VEGF), and monocyte chemoattractant
      protein (MCP)-1. The effects of CdM(Hyp) on hypoxic HAECs were partially
      duplicated by the addition of IL-6 in a dose-dependent manner; however, anti-IL
      6, anti-MCP-1, and anti-VEGF blocking antibodies added independently did not
      attenuate the effects. Also, addition of CdM(Hyp) activated the PI3K-Akt pathway;
      the levels of p-Akt and several of its downstream targets were increased by
      CdM(Hyp), and both the increase in p-Akt and the increase in angiogenesis were
      blocked by an inhibitor of PI3K-Akt or by expression of a dominant negative gene
      for PI3K. CdM(Hyp) also increased the levels of p-extracellular signal-regulated
      kinase (ERK), but there was a minimal effect on p-signal transducer and activator
      of transcription-3, and an inhibitor of the ERK1/2 pathway had no effect on
      hypoxia-induced apoptosis of the HAECs. The results are consistent with
      suggestions that administration of MSCs or factors secreted by MSCs may provide a
      therapeutic method of decreasing apoptosis and enhancing angiogenesis.

PMID- 17540859
TI  - Cysteine pairs in the third intracellular loop of the muscarinic m1 acetylcholine
      receptor play a role in agonist-induced internalization.
AB  - We determined the functional role of a small domain in the third intracellular
      loop of the human muscarinic M(1) (hM(1)) receptor. Using site-directed
      mutagenesis, several mutant hM(1) receptors were made possessing either a
      deletion or point mutations within the third intracellular loop domain
      (252)PETPPGRCCRCC(263). Wild-type and mutant hM(1) receptors were transiently
      expressed in Chinese hamster ovary cells, and the effects of each mutation on
      radioligand binding, agonist-mediated phosphoinositide hydrolysis, and agonist
      induced internalization were determined. The mutant receptors exhibited a modest
      reduction in affinity for [(3)H]N-methylscopolamine (pK(D) = approximately 9.0)
      and a moderately increased binding capacity relative to the wild-type receptor.
      This moderate increase in binding capacity was associated with small increases in
      the maximal response and potency of carbachol for eliciting phosphoinositide
      hydrolysis through the mutant receptors (pEC(50) = approximately 5.5) relative to
      wild-type (pEC(50) = 5.35 +/- 0.05). In contrast, carbachol-induced
      internalization of mutant hM(1) receptors possessing either C259A/C260A or
      C262A/C263A or both double point mutations was significantly reduced compared to
      the wild-type hM(1) receptor. Of the hM(1) receptor mutants tested, those
      possessing a C262D/C263D double point mutation had the least carbachol-induced
      internalization. The desensitization and down-regulation of receptors possessing
      either Cys/Ala or Cys/Asp double point mutations were similar to those observed
      for the wild-type hM(1) receptor. Collectively, these observations suggest that
      Cys pairs Cys259/Cys260 and Cys262/Cys263 play an important role in the agonist
      induced internalization of hM(1) receptors.

PMID- 17540860
TI  - Imaging the surface of Altair.
AB  - Spatially resolving the surfaces of nearby stars promises to advance our
      knowledge of stellar physics. Using optical long-baseline interferometry, we
      constructed a near-infrared image of the rapidly rotating hot star Altair with a
      resolution of <1 milliarcsecond. The image clearly reveals the strong effect of
      gravity darkening on the highly distorted stellar photosphere. Standard models
      for a uniformly rotating star cannot explain our findings, which appear to result
      from differential rotation, alternative gravity-darkening laws, or both.

PMID- 17540861
TI  - Sponge paleogenomics reveals an ancient role for carbonic anhydrase in
      skeletogenesis.
AB  - Sponges (phylum Porifera) were prolific reef-building organisms during the
      Paleozoic and Mesozoic approximately 542 to 65 million years ago. These ancient
      animals inherited components of the first multicellular skeletogenic toolkit from
      the last common ancestor of the Metazoa. Using a paleogenomics approach,
      including gene- and protein-expression techniques and phylogenetic
      reconstruction, we show that a molecular component of this toolkit was the
      precursor to the alpha-carbonic anhydrases (alpha-CAs), a gene family used by
      extant animals in a variety of fundamental physiological processes. We used the
      coralline demosponge Astrosclera willeyana, a "living fossil" that has survived
      from the Mesozoic, to provide insight into the evolution of the ability to
      biocalcify, and show that the alpha-CA family expanded from a single ancestral
      gene through several independent gene-duplication events in sponges and
      eumetazoans.

PMID- 17540862
TI  - Genome-wide mapping of in vivo protein-DNA interactions.
AB  - In vivo protein-DNA interactions connect each transcription factor with its
      direct targets to form a gene network scaffold. To map these protein-DNA
      interactions comprehensively across entire mammalian genomes, we developed a
      large-scale chromatin immunoprecipitation assay (ChIPSeq) based on direct
      ultrahigh-throughput DNA sequencing. This sequence census method was then used to
      map in vivo binding of the neuron-restrictive silencer factor (NRSF; also known
      as REST, for repressor element-1 silencing transcription factor) to 1946
      locations in the human genome. The data display sharp resolution of binding
      position [+/-50 base pairs (bp)], which facilitated our finding motifs and
      allowed us to identify noncanonical NRSF-binding motifs. These ChIPSeq data also
      have high sensitivity and specificity [ROC (receiver operator characteristic)
      area >/= 0.96] and statistical confidence (P <10(-4)), properties that were
      important for inferring new candidate interactions. These include key
      transcription factors in the gene network that regulates pancreatic islet cell
      development.

PMID- 17540863
TI  - How much more rain will global warming bring?
AB  - Climate models and satellite observations both indicate that the total amount of
      water in the atmosphere will increase at a rate of 7% per kelvin of surface
      warming. However, the climate models predict that global precipitation will
      increase at a much slower rate of 1 to 3% per kelvin. A recent analysis of
      satellite observations does not support this prediction of a muted response of
      precipitation to global warming. Rather, the observations suggest that
      precipitation and total atmospheric water have increased at about the same rate
      over the past two decades.

PMID- 17540864
TI  - Changes in innovation ecology.

PMID- 17540865
TI  - Paleontology. Mammoth-killer impact gets mixed reception from Earth scientists.

PMID- 17540866
TI  - Animal studies. NIH to end chimp breeding for research.

PMID- 17540867
TI  - Program evaluation. Researchers fault U.S. report critiquing education programs.

PMID- 17540868
TI  - Scientific workforce. U.S. immigration bill would extend warmer welcome to highly
      skilled.

PMID- 17540869
TI  - Space science. Stern looks for way out of NASA's budget squeeze.

PMID- 17540870
TI  - Higher education. Australian university is latest to pull up stakes in Singapore.

PMID- 17540871
TI  - Preparing teachers. A new twist on training teachers.

PMID- 17540872
TI  - Preparing teachers. BYU takes team approach led by a master teacher.

PMID- 17540873
TI  - Preparing teachers. Prime mover: Robert Clark.

PMID- 17540874
TI  - Preparing teachers. Junior high means a senior commitment.

PMID- 17540875
TI  - Preparing teachers. UTeach makes Marshall Hester a lifer.

PMID- 17540876
TI  - Preparing teachers. UTexas tells science majors: we want U (to) teach.

PMID- 17540877
TI  - Preparing teachers. Prime mover: Mary Ann Rankin.

PMID- 17540879
TI  - Preparing teachers. Prime mover: Richard McCray.

PMID- 17540878
TI  - Preparing teachers. Colorado also seeks impact on campus.

PMID- 17540880
TI  - Preparing teachers. Teaching for a living or for life.

PMID- 17540881
TI  - Preparing teachers. California heads down many roads in search of best training
      model.

PMID- 17540882
TI  - Biodiversity loss in the ocean: how bad is it?

PMID- 17540883
TI  - Problems of searching in Web databases.

PMID- 17540884
TI  - Comment on "Impacts of biodiversity loss on ocean ecosystem services".
AB  - Worm et al. (Research Articles, 3 November 2006, p. 787) used a power relation to
      predict a global collapse of fisheries by the year 2048. However, a linear
      regression of the data for the past 40 years yields an excellent fit, with a
      predicted date of collapse of 2114. Thus, long-term projections of fisheries
      collapse are highly dependent on the specific statistical model used.

PMID- 17540885
TI  - Comment on "Impacts of biodiversity loss on ocean ecosystem services".
AB  - Worm et al. (Research Articles, 3 November 2006, p. 787) reported an increasing
      proportion of fisheries in a "collapsed" state. We show that this may be an
      artifact of their definition of collapse as a fixed percentage of the maximum and
      that an increase in the number of managed fisheries could produce similar
      patterns as an increase in fisheries with catches below 10% of the maximum.

PMID- 17540886
TI  - Comment on "Impacts of biodiversity loss on ocean ecosystem services".
AB  - Worm et al. (Research Articles, 3 November 2006, p. 787) investigated the
      importance of biodiversity to marine ecosystem services across temporal and
      spatial scales. In projecting the extent of future fisheries collapse, we argue
      that the authors inappropriately extrapolated beyond their available observations
      and used data on marine reserves and fishery closures that are not representative
      of global fisheries.

PMID- 17540887
TI  - International security. Energy security for North Korea.

PMID- 17540888
TI  - Physics. Watching electrons break up.

PMID- 17540889
TI  - Immunology. The cutting edge of T cell selection.

PMID- 17540890
TI  - Anthropology. Walking on trees.

PMID- 17540891
TI  - Ocean science. Burial at sea.

PMID- 17540892
TI  - Atmospheric science. The monsoon's past.

PMID- 17540893
TI  - Plant science. Infectious heresy.

PMID- 17540894
TI  - Large-scale spatial-transmission models of infectious disease.
AB  - During transmission of seasonal endemic diseases such as measles and influenza,
      spatial waves of infection have been observed between large distant populations.
      Also, during the initial stages of an outbreak of a new or reemerging pathogen,
      disease incidence tends to occur in spatial clusters, which makes containment
      possible if you can predict the subsequent spread of disease. Spatial models are
      being used with increasing frequency to help characterize these large-scale
      patterns and to evaluate the impact of interventions. Here, I review several
      recent studies on four diseases that show the benefits of different
      methodologies: measles (patch models), foot-and-mouth disease (distance
      transmission models), pandemic influenza (multigroup models), and smallpox
      (network models). This review highlights the importance of the household in
      spatial studies of human diseases, such as smallpox and influenza. It also
      demonstrates the need to develop a simple model of household demographics, so
      that these large-scale models can be extended to the investigation of long-time
      scale human pathogens, such as tuberculosis and HIV.

PMID- 17540895
TI  - Seawater chemistry and early carbonate biomineralization.
AB  - The first appearances of aragonite and calcite skeletons in 18 animal clades that
      independently evolved mineralization during the late Ediacaran through the
      Ordovician (approximately 550 to 444 million years ago) correspond to intervals
      when seawater chemistry favored aragonite and calcite precipitation,
      respectively. Skeletal mineralogies rarely changed once skeletons evolved,
      despite subsequent changes in seawater chemistry. Thus, the selection of
      carbonate skeletal minerals appears to have been dictated by seawater chemistry
      at the time a clade first acquired its mineralized skeleton.

PMID- 17540896
TI  - 155,000 years of West African monsoon and ocean thermal evolution.
AB  - A detailed reconstruction of West African monsoon hydrology over the past 155,000
      years suggests a close linkage to northern high-latitude climate oscillations.
      Ba/Ca ratio and oxygen isotope composition of planktonic foraminifera in a marine
      sediment core from the Gulf of Guinea, in the eastern equatorial Atlantic (EEA),
      reveal centennial-scale variations of riverine freshwater input that are
      synchronous with northern high-latitude stadials and interstadials of the
      penultimate interglacial and the last deglaciation. EEA Mg/Ca-based sea surface
      temperatures (SSTs) were decoupled from northern high-latitude millennial-scale
      fluctuation and primarily responded to changes in atmospheric greenhouse gases
      and low-latitude solar insolation. The onset of enhanced monsoon precipitation
      lags behind the changes in EEA SSTs by up to 7000 years during glacial
      interglacial transitions. This study demonstrates that the stadial-interstadial
      and deglacial climate instability of the northern high latitudes exerts dominant
      control on the West African monsoon dynamics through an atmospheric linkage.

PMID- 17540897
TI  - Legumes symbioses: absence of Nod genes in photosynthetic bradyrhizobia.
AB  - Leguminous plants (such as peas and soybeans) and rhizobial soil bacteria are
      symbiotic partners that communicate through molecular signaling pathways,
      resulting in the formation of nodules on legume roots and occasionally stems that
      house nitrogen-fixing bacteria. Nodule formation has been assumed to be
      exclusively initiated by the binding of bacterial, host-specific lipochito
      oligosaccharidic Nod factors, encoded by the nodABC genes, to kinase-like
      receptors of the plant. Here we show by complete genome sequencing of two
      symbiotic, photosynthetic, Bradyrhizobium strains, BTAi1 and ORS278, that
      canonical nodABC genes and typical lipochito-oligosaccharidic Nod factors are not
      required for symbiosis in some legumes. Mutational analyses indicated that these
      unique rhizobia use an alternative pathway to initiate symbioses, where a purine
      derivative may play a key role in triggering nodule formation.

PMID- 17540898
TI  - Quantum register based on individual electronic and nuclear spin qubits in
      diamond.
AB  - The key challenge in experimental quantum information science is to identify
      isolated quantum mechanical systems with long coherence times that can be
      manipulated and coupled together in a scalable fashion. We describe the coherent
      manipulation of an individual electron spin and nearby individual nuclear spins
      to create a controllable quantum register. Using optical and microwave radiation
      to control an electron spin associated with the nitrogen vacancy (NV) color
      center in diamond, we demonstrated robust initialization of electron and nuclear
      spin quantum bits (qubits) and transfer of arbitrary quantum states between them
      at room temperature. Moreover, nuclear spin qubits could be well isolated from
      the electron spin, even during optical polarization and measurement of the
      electronic state. Finally, coherent interactions between individual nuclear spin
      qubits were observed and their excellent coherence properties were demonstrated.
      These registers can be used as a basis for scalable, optically coupled quantum
      information systems.

PMID- 17540899
TI  - Anisotropic violation of the Wiedemann-Franz law at a quantum critical point.
AB  - A quantum critical point transforms the behavior of electrons so strongly that
      new phases of matter can emerge. The interactions at play are known to fall
      outside the scope of the standard model of metals, but a fundamental question
      remains: Is the basic concept of a quasiparticle-a fermion with renormalized mass
      still valid in such systems? The Wiedemann-Franz law, which states that the ratio
      of heat and charge conductivities in a metal is a universal constant in the limit
      of zero temperature, is a robust consequence of Fermi-Dirac statistics. We report
      a violation of this law in the heavy-fermion metal CeCoIn5 when tuned to its
      quantum critical point, depending on the direction of electron motion relative to
      the crystal lattice, which points to an anisotropic destruction of the Fermi
      surface.

PMID- 17540900
TI  - Mars: a new core-crystallization regime.
AB  - The evolution of the martian core is widely assumed to mirror the characteristics
      observed for Earth's core. Data from experiments performed on iron-sulfur and
      iron-nickel-sulfur systems at pressures corresponding to the center of Mars
      indicate that its core is presently completely liquid and that it will not form
      an outwardly crystallizing iron-rich inner core, as does Earth. Instead,
      planetary cooling will lead to core crystallization following either a "snowing
      core" model, whereby iron-rich solids nucleate in the outer portions of the core
      and sink toward the center, or a "sulfide inner-core" model, where an iron
      sulfide phase crystallizes to form a solid inner core.

PMID- 17540901
TI  - Physical model for the decay and preservation of marine organic carbon.
AB  - Degradation of marine organic carbon provides a major source of atmospheric
      carbon dioxide, whereas preservation in sediments results in accumulation of
      oxygen. These processes involve the slow decay of chemically recalcitrant
      compounds and physical protection. To assess the importance of physical
      protection, we constructed a reaction-diffusion model in which organic matter
      differs only in its accessibility to microbial degradation but not its intrinsic
      reactivity. The model predicts that organic matter decays logarithmically with
      time t and that decay rates decrease approximately as 0.2 x t(-1) until burial.
      Analyses of sediment-core data are consistent with these predictions.

PMID- 17540902
TI  - Origin of human bipedalism as an adaptation for locomotion on flexible branches.
AB  - Human bipedalism is commonly thought to have evolved from a quadrupedal
      terrestrial precursor, yet some recent paleontological evidence suggests that
      adaptations for bipedalism arose in an arboreal context. However, the adaptive
      benefit of arboreal bipedalism has been unknown. Here we show that it allows the
      most arboreal great ape, the orangutan, to access supports too flexible to be
      negotiated otherwise. Orangutans react to branch flexibility like humans running
      on springy tracks, by increasing knee and hip extension, whereas all other
      primatesdothe reverse. Human bipedalism is thus less an innovation than an
      exploitation of a locomotor behavior retained from the common great ape ancestor.

PMID- 17540903
TI  - Complex I binding by a virally encoded RNA regulates mitochondria-induced cell
      death.
AB  - Human cytomegalovirus infection perturbs multiple cellular processes that could
      promote the release of proapoptotic stimuli. Consequently, it encodes mechanisms
      to prevent cell death during infection. Using rotenone, a potent inhibitor of the
      mitochondrial enzyme complex I (reduced nicotinamide adenine dinucleotide
      ubiquinone oxido-reductase), we found that human cytomegalovirus infection
      protected cells from rotenone-induced apoptosis, a protection mediated by a 2.7
      kilobase virally encoded RNA (beta2.7). During infection, beta2.7 RNA interacted
      with complex I and prevented the relocalization of the essential subunit genes
      associated with retinoid/interferon-induced mortality-19, in response to
      apoptotic stimuli. This interaction, which is important for stabilizing the
      mitochondrial membrane potential, resulted in continued adenosine triphosphate
      production, which is critical for the successful completion of the virus' life
      cycle. Complex I targeting by a viral RNA represents a refined strategy to
      modulate the metabolic viability of the infected host cell.

PMID- 17540904
TI  - Regulation of CD8+ T cell development by thymus-specific proteasomes.
AB  - Proteasomes are responsible for generating peptides presented by the class I
      major histocompatibility complex (MHC) molecules of the immune system. Here, we
      report the identification of a previously unrecognized catalytic subunit called
      beta5t. beta5t is expressed exclusively in cortical thymic epithelial cells,
      which are responsible for the positive selection of developing thymocytes.
      Although the chymotrypsin-like activity of proteasomes is considered to be
      important for the production of peptides with high affinities for MHC class I
      clefts, incorporation of beta5t into proteasomes in place of beta5 or beta5i
      selectively reduces this activity. We also found that beta5t-deficient mice
      displayed defective development of CD8(+) T cells in the thymus. Our results
      suggest a key role for beta5t in generating the MHC class I-restricted CD8(+) T
      cell repertoire during thymic selection.

PMID- 17540905
TI  - Pharmacological treatment of the overweight patient.

PMID- 17540906
TI  - Nonclassic endogenous novel [corrected] regulators of angiogenesis.
AB  - Angiogenesis, the process through which new blood vessels arise from preexisting
      ones, is regulated by several "classic" factors, among which the most studied are
      vascular endothelial growth factor (VEGF) and fibroblast growth factor-2 (FGF-2).
      In recent years, investigations showed that, in addition to the classic factors,
      numerous endogenous peptides play a relevant regulatory role in angiogenesis.
      Such regulatory peptides, each of which exerts well-known specific biological
      activities, are present, along with their receptors, in the blood vessels and may
      take part in the control of the "angiogenic switch." An in vivo and in vitro
      proangiogenic effect has been demonstrated for erythropoietin, angiotensin II
      (ANG-II), endothelins (ETs), adrenomedullin (AM), proadrenomedullin N-terminal 20
      peptide (PAMP), urotensin-II, leptin, adiponectin, resistin, neuropeptide-Y,
      vasoactive intestinal peptide (VIP), pituitary adenylate cyclase-activating
      polypeptide (PACAP), and substance P. There is evidence that the angiogenic
      action of some of these peptides is at least partly mediated by their stimulating
      effect on VEGF (ANG-II, ETs, PAMP, resistin, VIP and PACAP) and/or FGF-2 systems
      (PAMP and leptin). AM raises the expression of VEGF in endothelial cells, but
      VEGF blockade does not affect the proangiogenic action of AM. Other endogenous
      peptides have been reported to exert an in vivo and in vitro antiangiogenic
      action. These include somatostatin and natriuretic peptides, which suppress the
      VEGF system, and ghrelin, that antagonizes FGF-2 effects. Investigations on
      "nonclassic" regulators of angiogenesis could open new perspectives in the
      therapy of diseases coupled to dysregulation of angiogenesis.

PMID- 17540908
TI  - Two decision aids for mode of delivery among women with previous caesarean
      section: randomised controlled trial.
AB  - OBJECTIVES: To determine the effects of two computer based decision aids on
      decisional conflict and mode of delivery among pregnant women with a previous
      caesarean section. DESIGN: Randomised trial, conducted from May 2004 to August
      2006. SETTING: Four maternity units in south west England, and Scotland.
      PARTICIPANTS: 742 pregnant women with one previous lower segment caesarean
      section and delivery expected at >or=37 weeks. Non-English speakers were
      excluded. INTERVENTIONS: Usual care: standard care given by obstetric and
      midwifery staff. Information programme: women navigated through descriptions and
      probabilities of clinical outcomes for mother and baby associated with planned
      vaginal birth, elective caesarean section, and emergency caesarean section.
      Decision analysis: mode of delivery was recommended based on utility assessments
      performed by the woman combined with probabilities of clinical outcomes within a
      concealed decision tree. Both interventions were delivered via a laptop computer
      after brief instructions from a researcher. MAIN OUTCOME MEASURES: Total score on
      decisional conflict scale, and mode of delivery. RESULTS: Women in the
      information programme (adjusted difference -6.2, 95% confidence interval -8.7 to 
      3.7) and the decision analysis (-4.0, -6.5 to -1.5) groups had reduced decisional
      conflict compared with women in the usual care group. The rate of vaginal birth
      was higher for women in the decision analysis group compared with the usual care
      group (37% v 30%, adjusted odds ratio 1.42, 0.94 to 2.14), but the rates were
      similar in the information programme and usual care groups. CONCLUSIONS: Decision
      aids can help women who have had a previous caesarean section to decide on mode
      of delivery in a subsequent pregnancy. The decision analysis approach might
      substantially affect national rates of caesarean section. Trial Registration
      Current Controlled Trials ISRCTN84367722.

PMID- 17540909
TI  - Interventions to promote walking: systematic review.
AB  - OBJECTIVE: To assess the effects of interventions to promote walking in
      individuals and populations. DESIGN: Systematic review. DATA SOURCES: Published
      and unpublished reports in any language identified by searching 25 electronic
      databases, by searching websites, reference lists, and existing systematic
      reviews, and by contacting experts. REVIEW METHODS: Systematic search for and
      appraisal of controlled before and after studies of the effects of any type of
      intervention on how much people walk, the distribution of effects on walking
      between social groups, and any associated effects on overall physical activity,
      fitness, risk factors for disease, health, and wellbeing. RESULTS: We included 19
      randomised controlled trials and 29 non-randomised controlled studies.
      Interventions tailored to people's needs, targeted at the most sedentary or at
      those most motivated to change, and delivered either at the level of the
      individual (brief advice, supported use of pedometers, telecommunications) or
      household (individualised marketing) or through groups, can encourage people to
      walk more, although the sustainability, generalisability, and clinical benefits
      of many of these approaches are uncertain. Evidence for the effectiveness of
      interventions applied to workplaces, schools, communities, or areas typically
      depends on isolated studies or subgroup analysis. CONCLUSIONS: The most
      successful interventions could increase walking among targeted participants by up
      to 30-60 minutes a week on average, at least in the short term. From a
      perspective of improving population health, much of the research currently
      provides evidence of efficacy rather than effectiveness. Nevertheless,
      interventions to promote walking could contribute substantially towards
      increasing the activity levels of the most sedentary.

PMID- 17540910
TI  - Mental health consequences of long term conflict.

PMID- 17540911
TI  - Evaluation of HIV programmes.

PMID- 17540912
TI  - Drug resistant HIV.

PMID- 17540913
TI  - Improving health for the world's poor.

PMID- 17540914
TI  - Thromboprophylaxis for adults in hospital: Concern over guidelines.

PMID- 17540915
TI  - Thromboprophylaxis for adults in hospital: A mess for medical patients.

PMID- 17540916
TI  - Thromboprophylaxis for adults in hospital: Prophylaxis for medical inpatients is
      not entirely proven.

PMID- 17540917
TI  - Political illiteracy: Many, but not all.

PMID- 17540918
TI  - Multimorbidity's many challenges: A research priority in the UK.

PMID- 17540919
TI  - Thromboprophylaxis for adults in hospital: Improving use.

PMID- 17540920
TI  - Thromboprophylaxis for adults in hospital: Effective implementation of
      thromboprophylaxis strategies.

PMID- 17540922
TI  - Police look abroad for expert to advise on case of alleged salt poisoning.

PMID- 17540923
TI  - Out of hours GP services are criticised after death of patient.

PMID- 17540924
TI  - Assembly gets into wrangle over wording of junk food warning.

PMID- 17540925
TI  - Head of Red Cross pleads for medical missions not to be attacked.

PMID- 17540926
TI  - Undertakers offer cash incentive for organ donation.

PMID- 17540927
TI  - NHS hearing aid services vary unacceptably in quality, MPs say.

PMID- 17540928
TI  - UK will lose clinical trials if electronic records system is delayed, ABPI warns.

PMID- 17540929
TI  - AIDS expert doubts vaccine will be found in near future.

PMID- 17540930
TI  - People with AIDS are dying because of inadequate staffing, says MSF.

PMID- 17540932
TI  - World Health Assembly debates sharing of bird flu viruses for vaccines.

PMID- 17540933
TI  - Number of HIV infections is still rising despite prevention and treatment
      efforts, UN says.

PMID- 17540934
TI  - Gender disorder specialist is found guilty of serious professional misconduct.

PMID- 17540940
TI  - Independence day?

PMID- 17540941
TI  - Standing up for justice.

PMID- 17540942
TI  - Europe on the rocks.

PMID- 17540943
TI  - Monitoring and evaluation of programmes to prevent mother to child transmission
      of HIV in Africa.

PMID- 17540944
TI  - Rape and sexual assault.

PMID- 17540945
TI  - Skin biopsy: a new tool for diagnosing peripheral neuropathy.

PMID- 17540946
TI  - Assessment and initial management of feverish illness in children younger than 5
      years: summary of NICE guidance.

PMID- 17540947
TI  - 10-minute consultation: sinusitis.

PMID- 17540953
TI  - Islet surface heparinization prevents the instant blood-mediated inflammatory
      reaction in islet transplantation.
AB  - OBJECTIVE: In clinical islet transplantation, the instant blood-mediated
      inflammatory reaction (IBMIR) is a major factor contributing to the poor initial
      engraftment of the islets. This reaction is triggered by tissue factor and
      monocyte chemoattractant protein (MCP)-1, expressed by the transplanted
      pancreatic islets when the islets come in contact with blood in the portal vein.
      All currently identified systemic inhibitors of the IBMIR are associated with a
      significantly increased risk of bleeding or other side effects. To avoid systemic
      treatment, the aim of the present study was to render the islet graft blood
      biocompatible by applying a continuous heparin coating to the islet surface.
      RESEARCH DESIGN AND METHODS: A biotin/avidin technique was used to conjugate
      preformed heparin complexes to the surface of pancreatic islets. This endothelial
      like coating was achieved by conjugating barely 40 IU heparin per full-size
      clinical islet transplant. RESULTS: Both in an in vitro loop model and in an
      allogeneic porcine model of clinical islet transplantation, this heparin coating
      provided protection against the IBMIR. Culturing heparinized islets for 24 h did
      not affect insulin release after glucose challenge, and heparin-coated islets
      cured diabetic mice in a manner similar to untreated islets. CONCLUSIONS: This
      novel pretreatment procedure prevents intraportal thrombosis and efficiently
      inhibits the IBMIR without increasing the bleeding risk and, unlike other
      pretreatment procedures (e.g., gene therapy), without inducing acute or chronic
      toxicity in the islets.

PMID- 17540954
TI  - Variation of the transcription factor 7-like 2 (TCF7L2) gene predicts impaired
      fasting glucose in healthy young adults: the Cardiovascular Risk in Young Finns
      Study.

PMID- 17540955
TI  - Continuing stability of center differences in pediatric diabetes care: do
      advances in diabetes treatment improve outcome? The Hvidoere Study Group on
      Childhood Diabetes.
AB  - OBJECTIVE: To reevaluate the persistence and stability of previously observed
      differences between pediatric diabetes centers and to investigate the influence
      of demography, language communication problems, and changes in insulin regimens
      on metabolic outcome, hypoglycemia, and ketoacidosis. RESEARCH DESIGN AND
      METHODS: This was an observational cross-sectional international study in 21
      centers, with clinical data obtained from all participants and A1C levels assayed
      in one central laboratory. All individuals with diabetes aged 11-18 years (49.4%
      female), with duration of diabetes of at least 1 year, were invited to
      participate. Fourteen of the centers participated in previous Hvidoere Studies,
      allowing direct comparison of glycemic control across centers between 1998 and
      2005. RESULTS: Mean A1C was 8.2 +/- 1.4%, with substantial variation between
      centers (mean A1C range 7.4-9.2%; P < 0.001). There were no significant
      differences between centers in rates of severe hypoglycemia or diabetic
      ketoacidosis. Language difficulties had a significant negative impact on
      metabolic outcome (A1C 8.5 +/- 2.0% vs. 8.2 +/- 1.4% for those with language
      difficulties vs. those without, respectively; P < 0.05). After adjustement for
      significant confounders of age, sex, duration of diabetes, insulin regimen,
      insulin dose, BMI, and language difficulties, the center differences persisted,
      and the effect size for center was not reduced. Relative center ranking since
      1998 has remained stable, with no significant change in A1C. CONCLUSIONS: Despite
      many changes in diabetes management, major differences in metabolic outcome
      between 21 international pediatric diabetes centers persist. Different
      application between centers in the implementation of insulin treatment appears to
      be of more importance and needs further exploration.

PMID- 17540956
TI  - Diabetes and deafness: is it sufficient to screen for the mitochondrial 3243A>G
      mutation alone?

PMID- 17540957
TI  - Improved metabolic risk markers following two 6-month physical activity programs
      among socioeconomic marginalized women of Native American ancestry in Lima, Peru.

PMID- 17540958
TI  - Can fMRI measures of brain motor activation add significantly to other variables
      in the prediction of treatment response?

PMID- 17540959
TI  - CT/NIHSS mismatch for detection of salvageable brain in acute stroke triage
      beyond the 3-hour time window: overrated or undervalued?

PMID- 17540960
TI  - Community stroke education using mass media: past results and future
      implications.

PMID- 17540961
TI  - Do women have worse outcome after stroke caused by intracranial arterial
      stenosis?

PMID- 17540962
TI  - Motor and functional recovery after stroke: a comparison between 4 European
      rehabilitation centers.

PMID- 17540963
TI  - Explicit priority setting in clinical guidelines: the next frontier?

PMID- 17540964
TI  - Intravenous or intra-arterial thrombolysis?: it's time to find the right approach
      for the right patient.

PMID- 17540965
TI  - The EXCITE trial: a major step forward for restorative therapies in stroke.

PMID- 17540966
TI  - Predicting functional gains in a stroke trial.
AB  - BACKGROUND AND PURPOSE: A number of therapies in development for patients with
      central nervous system injury aim to reduce disability by improving function of
      surviving brain elements rather than by salvaging tissue. The current study
      tested the hypothesis that, after adjusting for a number of clinical assessments,
      a measure of brain function at baseline would improve prediction of behavioral
      gains after treatment. METHODS: Twenty-four patients with chronic stroke
      underwent baseline clinical and functional MRI assessments, received 6 weeks of
      rehabilitation therapy with or without investigational motor cortex stimulation,
      and then had repeat assessments. Thirteen baseline clinical/radiological measures
      were evaluated for ability to predict subsequent trial-related gains. RESULTS:
      Across all patients, bivariate analyses found that greater trial-related
      functional gains were predicted by (1) smaller infarct volume, (2) greater
      baseline clinical status, and (3) lower degree of activation in stroke-affected
      motor cortex on baseline functional MRI. When these 3 variables were further
      assessed using multivariate linear regression modeling, only lower motor cortex
      activation and greater clinical status at baseline remained significant
      predictors. Note that lower baseline motor cortex activation was also associated
      with larger increases in motor cortex activation after treatment. CONCLUSIONS:
      Lower motor cortex activity at baseline predicted greater behavioral gains after
      therapy, even after controlling for a number of clinical assessments. The boosts
      in cortical activity that paralleled behavioral gains suggest that in some
      patients, low baseline cortical activity represents underuse of surviving
      cortical resources. A measure of brain function might be important for optimal
      clinical decision-making in the context of a restorative intervention.

PMID- 17540967
TI  - Can mass media influence emergency department visits for stroke?
AB  - BACKGROUND AND PURPOSE: Television advertising has been associated with
      significant increases in the knowledge of the warning signs of stroke among
      Ontarians aged 45 and older. However, to date there has been little data on the
      relationship between knowledge of the warning signs of stroke and behavior.
      METHODS: Data on presentation to regional and enhanced district stroke center
      emergency departments were obtained from the Registry of the Canadian Stroke
      Network for a 31-month period between mid 2003 and the beginning of 2006. Public
      opinion polling was used to track knowledge of the warning signs of stroke among
      Ontarians aged 45 and older. RESULTS: The public's awareness of the warning signs
      of stroke increased during 2003 to 2005, decreasing in 2006 after a 5-month
      advertising blackout. There was a significant increase in the mean number of
      emergency department visits for stroke over the study period. A campaign effect
      independent of year was observed for total presentations, presentation within 5
      hours of last seen normal, and presentation within 2.5 hours. For TIAs there was
      a strong campaign effect but no change in the number of presentations by year.
      CONCLUSIONS: Continuous advertising may be required to build and sustain public
      awareness of the warning signs of stroke. There are many factors that may
      influence presentation for stroke and awareness of the warning signs may be only
      one. However, results of this study suggest there may be an important correlation
      between the advertising and emergency department presentations with stroke,
      particularly for TIAs.

PMID- 17540968
TI  - Motor and functional recovery after stroke: a comparison of 4 European
      rehabilitation centers.
AB  - BACKGROUND AND PURPOSE: Outcome after first stroke varies significantly across
      Europe. This study was designed to compare motor and functional recovery after
      stroke between four European rehabilitation centers. METHODS: Consecutive stroke
      patients (532 patients) were recruited. They were assessed on admission and at 2,
      4, and 6 months after stroke with the Barthel Index, Rivermead Motor Assessment
      of Gross Function, Rivermead Motor Assessment of Leg/Trunk, Rivermead Motor
      Assessment of Arm, and Nottingham Extended Activities of Daily Living (except on
      admission). Data were analyzed using random effects ordinal logistic models
      adjusting for case-mix and multiple testing. RESULTS: Patients in the UK center
      were more likely to stay in lower Rivermead Motor Assessment of Gross Function
      classes compared with patients in the German center (DeltaOR, 2.4; 95% CI, 1.3 to
      4.3). In the Swiss center, patients were less likely to stay in lower Nottingham
      Extended Activities of Daily Living classes compared with patients in the UK
      center (DeltaOR, 0.7; 95% CI, 0.5 to 0.9). The latter were less likely to stay in
      lower Barthel Index classes compared with the patients in the German center
      (DeltaOR, 0.6; 95%CI, 0.4 to 0.8). Recovery patterns of Rivermead Motor
      Assessment of Leg/Trunk and Rivermead Motor Assessment of Arm were not
      significantly different between centers. CONCLUSIONS: Gross motor and functional
      recovery were better in the German and Swiss centers compared with the UK center,
      respectively. Personal self-care recovery was better in the UK compared with the
      German center. Previous studies in the same centers indicated that German and
      Swiss patients received more therapy per day. This was not the result of more
      staff but of a more efficient use of human resources. This study indicates
      potential for improving rehabilitation outcomes in the UK and Belgian centers.

PMID- 17540969
TI  - Gender differences in outcomes among patients with symptomatic intracranial
      arterial stenosis.
AB  - BACKGROUND AND PURPOSE: There are limited and conflicting data on gender
      differences in clinical outcomes among patients with symptomatic intracranial
      arterial stenosis. This study examined gender differences in patients enrolled in
      the Warfarin-Aspirin Symptomatic Intracranial Disease (WASID) Study. METHODS:
      Participants were 569 men and women with symptomatic intracranial arterial
      stenosis. They were followed-up for the occurrence of ischemic stroke and the
      combined end point of stroke or vascular death from February 1999 through July
      2003 (mean follow-up, 1.8 years). RESULTS: Two-year rates of the primary end
      point were 28.4% and 16.6% for women and men, respectively. Cumulative
      probabilities of the outcomes over time were estimated by the Kaplan-Meier
      product-limit method and were compared between men and women with the use of the
      log-rank test. Cox proportional hazards regression analyses were used to estimate
      the hazard ratio of gender (women to men) for ischemic stroke and for the primary
      end point. The probabilities of ischemic stroke (P=0.005) and of the combined end
      point of stroke or vascular death (P=0.017) over time were significantly higher
      in women than men. Women had a greater multivariate-adjusted risk for ischemic
      stroke (HR, 1.85; 95% CI, 1.14 to 3.01; P=0.013) and for the combined end point
      of stroke or vascular death (HR, 1.58; 95% CI, 1.01 to 2.48; P=0.045).
      CONCLUSIONS: Women with symptomatic intracranial arterial stenosis are at
      significantly greater risk for ischemic stroke and for the combined end point of
      stroke or vascular death. These findings suggest the need for vigorous screening
      of risk factors and for aggressive management of risk factors and stroke in
      women. They also suggest the need to ensure adequate numbers of women in clinical
      trials designed to explore new and promising therapies for intracranial arterial
      stenosis.

PMID- 17540970
TI  - Beyond conventional stroke guidelines: setting priorities.
AB  - BACKGROUND AND PURPOSE: Priorities in the care of stroke patients are often
      intuitive. An open and translucent priority-setting procedure would benefit
      patients, professionals, and decision-makers. Prioritization is an innovative
      part of the new Swedish national stroke guidelines. METHODS: Working groups
      identified diagnostic procedures, interventions and therapies in stroke care,
      assessed each one according to severity (needs), effect of action, level of
      scientific evidence and cost-effectiveness. The items were then ranked into
      priority groups from 1 (highest) to 10 (lowest). Procedures lacking evidence for
      routine clinical use were also identified (and entered a do-not-do list), as well
      as procedures in research and development. Resource allocations resulting from
      the priority-setting process were identified. RESULTS: Of 102 core procedures
      identified, 50 were assigned to high-priority groups (1-3), 29 to moderate
      priority groups (4-7) and 23 to low priority groups (8-10). Almost a quarter were
      graded 8 to 10, indicating that they may not necessarily be applied if resources
      are scarce. Twenty-eight procedures were assigned to the do-not-do list and 16 to
      the research and development list. CONCLUSIONS: In stroke services, it is
      possible to identify not only diagnostic procedures and interventions with high
      priority, but also a considerable number of items used today that have low
      priority or should not be used at all. Strict adherence to the guidelines would
      result in a substantial reallocation of resources from low-priority to high
      priority areas.

PMID- 17540971
TI  - CT-NIHSS mismatch does not correlate with MRI diffusion-perfusion mismatch.
AB  - BACKGROUND AND PURPOSE: MRI diffusion-perfusion mismatch may identify patients
      for thrombolysis beyond 3 hours. However, MRI has limited availability in many
      hospitals. We investigated whether mismatch between the Alberta Stroke Program
      Early CT Score (ASPECTS) and the NIH Stroke Scale (NIHSS) correlates with MRI
      diffusion-perfusion mismatch. METHODS: We retrospectively analyzed a cohort of
      consecutive acute ischemic stroke patients who underwent MRI and CT at admission.
      NIHSS was performed by the admitting physician. MRI and CT were reviewed by 2
      blinded expert raters. Degree of MRI mismatch was defined as present (> 25%) or
      absent (<25%). Univariate and multivariate analyses were performed to determine
      characteristics associated with MRI mismatch. Probability of MRI mismatch was
      calculated for all combinations of ASPECTS and NIHSS cutoff scores. RESULTS:
      Included in the analysis were 143 patients. Median NIHSS on admission was 4 (IQR,
      2 to 10); median ASPECTS was 10 (IQR, 9 to 10). Median time to completion of MRI
      and CT was 4.5 (2.5 to 13.9) hours after onset. CT and MRI were separated by a
      median of 35 (IQR, 29 to 44) minutes. MRI mismatch was present in 41% of
      patients. In multivariate analysis, only shorter time-to-scan (OR, 0.96 per hour;
      95% CI, 0.92 to 1.0; P=0.043) was associated with MRI mismatch. There was no
      combination of NIHSS and ASPECTS thresholds that was significantly associated
      with MRI mismatch. CONCLUSIONS: ASPECTS-NIHSS mismatch did not correlate with MRI
      diffusion-perfusion mismatch in this clinical cohort. MRI mismatch was associated
      with decreasing time from stroke onset to scan.

PMID- 17540972
TI  - The metabolic syndrome and stroke: potential treatment approaches.

PMID- 17540973
TI  - Debunking 7 myths that hamper the realization of randomized controlled trials on
      intra-arterial thrombolysis for acute ischemic stroke.
AB  - BACKGROUND AND PURPOSE: Although intravenous (IV) thrombolysis is the standard
      treatment for patients with ischemic stroke occurring within 3 hours from symptom
      onset, a few interventional neuroradiologists have been treating this category of
      patients by an intra-arterial (IA) route for >25 years. However, evidence is
      still required to support the clinical feeling that IA treatment, which needs
      longer time and greater complexity, leads to a better outcome. Therefore, the
      objective of the present review was to analyze beliefs and myths underlying the
      selection of patients for IA thrombolysis. METHODS: We identified and debunked
      the following myths on IA thrombolysis: (1) IA thrombolysis works better than IV
      because it achieves higher recanalization rates; (2) IA thrombolysis works better
      than IV after the 3-hour window; (3) IA thrombolysis works better than IV in
      vertebrobasilar stroke; (4) carotid duplex, transcranial doppler, CT angiography,
      or MRA should be used to screen for major vessel occlusion treatable with IA
      thrombolysis; (5) to be treated with IA thrombolysis, patients should be selected
      with diffusion/perfusion MRI; (6) IA thrombolysis should be used as a "rescue"
      therapy for IV thrombolysis; and (7) the efficacy of IA thrombolysis depends on
      the thrombolytic agent or the device used. CONCLUSIONS: Evidence on acute stroke
      management with IA thrombolysis is scant. Therefore, neither clinicians nor
      patients have enough information to make truly informed decisions about the most
      appropriate treatment. Only randomized controlled trials can clear uncertainties
      about the possible superiority of IA over IV thrombolysis. Regretfully, case
      series on IA treatment have limited the organization of such trials and have only
      favored the spread of myths.

PMID- 17540974
TI  - Role of Dicer and Drosha for endothelial microRNA expression and angiogenesis.
AB  - MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression by
      binding to the cellular transcript leading to translational repression or
      degradation of the target mRNA. Dicer and Drosha are the miRNA processing enzymes
      that are required for the maturation of miRNAs. Here, we investigated the role of
      Dicer and Drosha for angiogenesis. Endothelial cells were transfected with siRNA
      against Dicer and Drosha to inhibit miRNA biogenesis. Genetic silencing of Dicer
      and Drosha significantly reduced capillary sprouting of endothelial cells and
      tube forming activity. Migration of endothelial cells was significantly decreased
      in Dicer siRNA-transfected cells, whereas Drosha siRNA had no effect. Silencing
      of Dicer but not of Drosha reduced angiogenesis in vivo. Next, we attempted to
      identify miRNAs expressed in endothelial cells. A screening analysis of 168 human
      miRNAs using real-time PCR revealed that members of the let-7 family, mir-21, mir
      126, mir-221, and mir-222 are highly expressed in endothelial cells. Dicer and
      Drosha siRNA reduced lef-7f and mir-27b expression. Inhibitors against let-7f and
      mir-27b also reduced sprout formation indicating that let-7f and mir-27b promote
      angiogenesis by targeting antiangiogenic genes. In silico analysis of predicted
      targets for let-7 cluster identified the endogenous angiogenesis inhibitor
      thrombospondin-1. Indeed, Dicer and Drosha siRNA significantly increased the
      expression of thrombospondin-1. Taken together, transient reduction of the miRNA
      regulating enzyme Dicer impairs angiogenesis in vitro and in vivo, whereas Drosha
      siRNA induced a minor antiangiogenic effect in vitro and was not effective in
      vivo. The let-7 family and mir-27b appear to be attractive targets for modulating
      angiogenesis.

PMID- 17540975
TI  - Organization of ventricular fibrillation in the human heart.
AB  - Sudden cardiac death is a major cause of death in the industrialized world,
      claiming approximately 300,000 victims annually in the United States alone. In
      most cases, sudden cardiac death is caused by ventricular fibrillation (VF).
      Experimental studies in large animal hearts have shown that the uncoordinated
      contractions during VF are caused by large numbers of chaotically wandering
      reentrant waves of electrical activity. However, recent clinical data on VF in
      the human heart seem to suggest that human VF may have a markedly different
      organization. Here, we use a detailed model of the human ventricles, including a
      detailed description of cell electrophysiology, ventricular anatomy, and fiber
      direction anisotropy, to study the organization of human VF. We show that
      characteristics of our simulated VF are qualitatively similar to the clinical
      data. Furthermore, we find that human VF is driven by only approximately 10
      reentrant sources and thus is much more organized than VF in animal hearts of
      comparable size, where VF is driven by approximately 50 sources. We investigate
      the influence of anisotropy ratio, tissue excitability, and restitution
      properties on the number of reentrant sources driving VF. We find that the number
      of rotors depends strongest on minimum action potential duration, a property that
      differs significantly between human and large animal hearts. Based on these
      findings, we suggest that the simpler spatial organization of human VF relative
      to VF in large animal hearts may be caused by differences in minimum action
      potential duration. Both the simpler spatial organization of human VF and its
      suggested cause may have important implications for treating and preventing this
      dangerous arrhythmia in humans.

PMID- 17540976
TI  - Stage-specific role of endogenous Smad2 activation in cardiomyogenesis of
      embryonic stem cells.
AB  - The role of Smads and their specific ligands during cardiomyogenesis in ES cells
      was examined. Smad2 was activated bimodally in the early and late phases of
      cardiac differentiation, whereas Smad1 was activated after the middle phase.
      Nodal and Cripto were expressed in the early stage and then downregulated,
      whereas transforming growth factor-beta and activin were expressed only in the
      late phase. Suppression of early Smad2 activation by SB-431542 produced complete
      inhibition of endodermal and mesodermal induction but augmented neuroectodermal
      differentiation, followed by poor cardiomyogenesis, whereas inhibition during the
      late phase alone promoted cardiomyogenesis. Inhibitory effect of Smad2 on
      cardiomyogenesis in the late phase was mainly mediated by transforming growth
      factor-beta, and inhibition of transforming growth factor-beta-mediated Smad2
      activation resulted in a greater replicative potential in differentiated cardiac
      myocytes and enhanced differentiation of nonmyocytes into cardiac myocytes. Thus,
      endogenous Smad2 activation is indispensable for endodermal and mesodermal
      induction in the early phase. In the late phase, endogenous transforming growth
      factor-beta negatively regulates cardiomyogenesis through Smad2 activation by
      modulating proliferation and differentiation of cardiac myocytes.

PMID- 17540977
TI  - Angiopoietin-2 impairs revascularization after limb ischemia.
AB  - Angiopoietins play important roles in the formation of neovessels and complex
      vascular networks. Angiopoietin (Ang)-1 and Ang-2 belong to a family of growth
      factors that display opposing effects on the activation of Tie2 (tyrosine kinase
      with immunoglobulin and epidermal growth factor homology domain 2). Endothelial
      Ang-2 expression is associated with vessel destabilization and regulates a
      balance between vascular regression and growth. To elucidate, in particular, the
      role of Ang-2 after arterial artery occlusion in the mouse limb, we applied a
      transgenic animal model with targeted Ang-2 expression in endothelial cells. We
      show here that restoration of blood flow in Ang-2:Tie1 transgenic mice is
      dramatically impaired when Ang-2 expression is induced in the vasculature. The
      defective restoration of perfusion in Ang-2 transgenic mice is evidenced by
      reduced collateral artery growth, which typically occurs to compensate for flow
      deficits after occlusion of the large conductance artery. Furthermore, reduced
      movement capacities and higher incidents of necrosis are consequently observed in
      the transgenic limbs as compared with controls. Mechanistically, the observed
      effects are attributed to defective smooth muscle cell recruitment in Ang-2
      transgenic mice. Moreover, distinct Ang-2 levels in the genetically modified
      animals clearly correlated with the magnitude of reduced perfusion. In
      conclusion, our studies define Ang-2 as an important molecule for the progression
      of collateral artery growth and angiogenesis during ischemia and suggest precise
      Ang-2 dosage activities to accomplish blood vessel growth.

PMID- 17540978
TI  - Liver X receptor activation potentiates the lipopolysaccharide response in human
      macrophages.
AB  - Macrophages play a central role in host defense against pathogen microbes by
      recognizing bacterial components, resulting in the activation of an arsenal of
      anti-microbial effectors. Toll-like receptor (TLR)-4 mediates the recognition of
      lipopolysaccharide, a pathogen-associated molecular pattern from gram-negative
      bacteria. Activation of the TLR-4 signaling pathway by lipopolysaccharide
      increases antibacterial effects by inducing secretion of cytokines that activate
      an immune inflammatory response and by generating bactericidal reactive oxygen
      species via the NADPH oxidase system. Liver X Receptors (LXRs) are nuclear
      receptors controlling cholesterol homeostasis and inflammation in macrophages. In
      addition, LXRs are critical for macrophage survival and play a role in the innate
      immune response in the mouse. In this study, we investigated whether LXR
      activation also regulates host defense mechanisms in human macrophages. In
      primary human macrophages, oxidized LDL and synthetic LXR ligands increased TLR-4
      gene expression. Transient transfection assays, gel shift and chromatin
      immunoprecipitation analysis indicated that LXRs induce human TLR-4 promoter
      activity by binding to a DR4-type LXR response element. LXR induction of TLR-4
      mRNA was followed by an induction of TLR-4 protein expression. Moreover, although
      short-term pretreatment with LXR agonists significantly reduced the inflammatory
      response induced by lipopolysaccharide, pretreatment of macrophages for 48 hours
      with LXR agonists resulted in an enhanced lipopolysaccharide response. Finally,
      LXR activation increased reactive oxygen species generation by enhancing the
      expression of NADPH oxidase subunits. These data provide evidence for an
      immunomodulatory function of LXRs in human macrophages via mechanisms distinct
      from those previously identified in mouse macrophages.

PMID- 17540979
TI  - Differential ventilation with spontaneous respiration for bilateral emphysema.
AB  - In patients with bilateral bullous disease and empyema in one lung, controlled
      ventilation may be hazardous and result in severe hypoxia. A 50-year-old man with
      bullous disease and thoracic empyema on the left side was operated on under
      general anesthesia with spontaneous respiration using differential lung
      ventilation.

PMID- 17540980
TI  - Stanford type A aortic dissection with Child B liver cirrhosis.
AB  - Cardiac surgery using cardiopulmonary bypass in patients with advanced liver
      cirrhosis has been infrequently performed, and reported to be too risky. Aortic
      dissection accompanied with liver cirrhosis is extremely rare. A 61-year-old
      woman who had aortic dissection and Child B liver cirrhosis underwent ascending
      aorta replacement. Liver protection during cardiopulmonary bypass was
      successfully accomplished by moderate hypothermia and use of an aortic occlusion
      balloon to maintain sufficient hepatic blood flow.

PMID- 17540981
TI  - Strategy for adult aortic coarctation complicated by coronary artery disease.
AB  - Aortic coarctation in adults is sometimes associated with a fragile aortic wall
      and may be complicated by coronary artery disease and ascending aortic dilation.
      Successful management of aortic coarctation in a 45-year-old man with coronary
      artery disease is described. Tube graft replacement was carried out without cross
      clamping, under circulatory arrest with axillary artery and graft inflow.

PMID- 17540982
TI  - Safe treatment of post thoracotomy seroma.
AB  - Postoperative seroma is a common complication after muscle-sparing lateral
      thoracotomy. The main cause is considered to be the result of subcutaneous flap
      mobilization. We present a case of seroma which occurred following a
      pneumonectomy owing to subcutaneous flooding with pleural fluid, which was
      successfully treated by subclavian catheter insertion. The technical aspect of
      the procedure is described.

PMID- 17540983
TI  - New strategy for cardiac repair: genetically modified skeletal myoblasts.

PMID- 17540984
TI  - Proteomics of ascending aortic aneurysm with bicuspid or tricuspid aortic valve.
AB  - Bicuspid aortic valve is often associated with lesions of the ascending aorta,
      which differ histologically from those in tricuspid valve patients. We undertook
      proteomic analyses to assess differences at the proteome level. Aortic samples
      were collected from 20 patients undergoing aortic valve and/or ascending aortic
      replacement; 9 had a bicuspid valve: 5 with aortic aneurysm (diameter > 50 mm)
      and 4 without dilation; 11 had a tricuspid valve: 6 with aortic aneurysm and 5
      without dilation. Patients with histologically proven connective tissue disorders
      were excluded. Samples were dissected, solubilized, and subjected to 2
      dimensional gel electrophoresis. Gel patterns showed an average of 580 protein
      spots in samples from bicuspid valve patients, and 564 spots in those with
      tricuspid valves. Comparative analysis revealed a correlation coefficient of 0.93
      for protein expression in the bicuspid valve group compared to the tricuspid
      group. Three protein spots were significantly over-expressed and 4 were
      significantly down-regulated in the bicuspid group compared to the tricuspid
      group. The lowest correlation in protein expression was between non-dilated
      aortic tissues. These differences between aortic tissues of bicuspid and
      tricuspid valve patients suggest that mechanisms of aortic dilation might differ,
      at least in part, between such patients.

PMID- 17540985
TI  - Peratrial closure of atrial septal defects without cardiopulmonary bypass.
AB  - The objective of this study was to introduce a new technique for occlusion of an
      atrial septal defect without cardiopulmonary bypass, using a modified Amplatzer
      device. Between October 2004 and November 2005, 96 secundum atrial septal defects
      in 83 patients were occluded by this method. A 3-cm incision in the right 4(th)
      intercostal space and a minithoracotomy were performed. Via this incision, the
      right atrium was exposed and the septal closure device was deployed under
      transesophageal echocardiographic guidance. The sizes of the defects ranged from
      10 to 39 mm. The mean device size was 34.1 +/- 9 mm (12-46 mm). There was no
      operative mortality and no major morbidity on follow-up of 3-15 months. This new
      minimally invasive method of secundum atrial septal defect closure is safe and
      cosmetically superior to conventional surgery. Avoidance of cardiopulmonary
      bypass can reduce recovery time and complications. The indications are more
      extensive than percutaneous transcatheter closure, and the results are
      encouraging.

PMID- 17540986
TI  - Near-infrared spectroscopy monitoring of brain oxygen in infant cardiac surgery.
AB  - The use of near-infrared spectroscopy for monitoring cerebral oxygenation during
      different types of cardiopulmonary bypass was evaluated in 24 patients aged 5 to
      13 months. They underwent open-heart surgery under cardiopulmonary bypass with
      moderate hypothermia, deep hypothermia with low flow, or deep hypothermia with
      circulatory arrest. Near-infrared spectroscopy data were compared with
      electroencephalography and biochemical indicators (neuron-specific enolase,
      lactate). Near-infrared spectroscopy data showed no correlation with biochemical
      indicators in patients undergoing cardiopulmonary bypass with moderate
      hypothermia or deep hypothermia with low flow. In the deep hypothermia with
      circulatory arrest group, the oxygenated hemoglobin signal declined to a nadir
      during circulatory arrest. The period from reaching the nadir until reperfusion
      and the minimum values of oxygenated hemoglobin correlated closely with increases
      in neuron-specific enolase and lactate. All patients with an oxygenated
      hemoglobin-signal nadir time < 35 min were free from behavioral evidence of brain
      injury. The oxygenated hemoglobin-signal nadir time may be useful in predicting
      the safe duration of circulatory arrest.

PMID- 17540987
TI  - Omental transposition: the final solution for major sternal wound infection.
AB  - Sternal osteomyelitis after median sternotomy for cardiac surgery is associated
      with considerable morbidity and mortality. The ideal reconstruction after sternal
      debridement is still debated. From 2000 to 2004, we treated 15 patients for
      sternal osteomyelitis (type IIIB, IVA, IVB) after median sternotomy for cardiac
      surgery. Total or partial resection of the sternum and extensive debridement were
      performed in all cases. The defect was covered by omental transposition. In 11
      cases, a single-stage operation took place, and a two-stage procedure was
      employed in 4. All patients had antibiotics postoperatively. There were 3 (20%)
      deaths due to cardiac failure. Hospital stay ranged from 21 to 45 days. Transient
      paradoxical movement of the anterior chest wall disappeared within one month. No
      recurrence was observed during 6 to 24 months of follow-up. Radical debridement
      along with omental flap transposition provides definitive control of the
      infection in cases of failure of other semi-conservative or surgical
      interventions. Prognosis depends on the general condition of the patient.

PMID- 17540988
TI  - Nicorandil attenuates reperfusion injury after long cardioplegic arrest.
AB  - The cardioprotective efficacy of nicorandil in cardiac surgery was determined
      using a surgically relevant 4-hr cardioplegic arrest model. Each isolated rabbit
      heart was parabiotically blood-perfused using a modified Langendorff column. The
      magnitude of left ventricular developed pressure and rate of change of developed
      pressure over time were measured before (baseline) and after ischemia. Nicorandil
      was administered either pre-ischemia, post-ischemia, pre/post-ischemia, or
      continuously (before, during, and after ischemia). The endothelium of the
      coronary artery was observed by scanning electron microscopy. Serum
      myeloperoxidase activities were also measured. Although pretreatment with
      nicorandil did not affect recovery of developed pressure, administration of
      nicorandil after ischemia, or before and after ischemia, enhanced the recovery of
      developed pressure. Serum myeloperoxidase activity was decreased in the pre/post
      ischemia and continuous groups. Endothelial reperfusion injury decreased in all
      nicorandil-treated groups. Administration of nicorandil attenuated ischemia
      reperfusion injury of the myocardium and coronary endothelium while ameliorating
      leukocyte activation. In the event of unexpected prolonged cardioplegic arrest,
      administration of nicorandil, even just after declamping, may improve cardiac
      function. However, pre-ischemia administration alone was not helpful in the heart
      subjected to prolonged cardioplegic arrest.

PMID- 17540989
TI  - Mitral valve repair for extended commissural prolapse involving complex prolapse.
AB  - We reviewed our experience of mitral valve repair techniques for extended
      commissural prolapse involving complex prolapse of either or both leaflets, due
      to chordal rupture or elongation. Between June 1991 and January 2005, 21 of 210
      patients who underwent mitral valve repair for mitral regurgitation had extended
      commissural prolapse involving either or both of the anterior and posterior
      leaflets. There were 17 (81%) patients with degenerative and 4 (19%) with
      infective endocarditis. The distribution of diseased mitral commissural lesions
      was: posteromedial commissure in 14 (67%) patients, anterolateral in 6 (29%), and
      bilateral in 1 (5%). Reconstructive techniques included leaflet folding plasty in
      10, resection-suture in 6, the sliding technique in 2, commissuroplasty in 2, and
      chordal shortening in 1. There were no perioperative deaths; postoperative mitral
      regurgitation was none or trivial in 19 patients and mild in 2. The mean follow
      up period was 54 months (range, 2-155 months), and no patient required re
      operation. There was one late death from a noncardiac cause at 103 months. Mitral
      valve repair for extended commissural prolapse is satisfactory. We consider
      leaflet folding plasty and its modification to be effective in patients who
      require extensive leaflet resection in the commissural area.

PMID- 17540990
TI  - Interleukin-4 C-590T polymorphism has no role in coronary artery bypass surgery.
AB  - Interleukin-4 exerts anti-inflammatory effects through decreased macrophage
      production of tumor necrosis factor-alpha and interleukin-1 beta. We investigated
      genetic predisposition in the interleukin-4 response to coronary
      revascularization and studied the association between C-590T polymorphism,
      interleukin-4 levels, and outcome of surgery. DNA was obtained from 96
      consecutive patients undergoing elective coronary revascularization. Patients
      were genotyped for interleukin-4 C-590T polymorphism using a sequence-specific
      primer polymerase chain reaction. Interleukin-4 levels were measured using an
      enzyme-linked immunosorbent assay in serum samples taken 3 hr postoperatively.
      The frequency of interleukin-4 C-590T genotypes CC, CT, and TT was 33.3%, 27.1%,
      and 39.6%, respectively. Patients with the TT genotype had significantly higher
      circulating levels of interleukin-4 (3.4 +/- 4.6 pg x mL(-1)) postoperatively
      compared to CC (2.5 +/- 0.1 pg x mL(-1)) and CT (2.7 +/- 0.5 pg x mL(-1))
      genotypes. Interleukin-4 C-590T polymorphism is the main determinant of
      postoperative interleukin-4 levels. The TT genotype is the highest producer of
      interleukin-4. Neither the genotype nor the serum levels seem to play any role in
      recovery from coronary artery bypass surgery.

PMID- 17540991
TI  - Pharmacological prevention of the deleterious effects of cardiopulmonary bypass.
AB  - Indomethacin is a known immune modulator that inhibits cyclooxygenase. Studies
      indicate that ketoconazole, a selective lipoxygenase and thromboxane A(2)
      synthetase inhibitor, can prevent activation of the inflammatory cascade by
      inhibition of proinflammatory mediators. This study was designed to determine if
      ketoconazole or indomethacin could reduce the adverse effects of extracorporeal
      circulation. As a double-blind prospective study, 76 patients were randomized
      into 3 groups according to preoperative medication: indomethacin, ketoconazole,
      and placebo groups, with 25, 26, and 25 patients, respectively. Four types of
      parameters were evaluated preoperatively and up to 24 hr after cardiac surgery in
      all patients: inflammatory (complement C3 and C4, C-reactive protein,
      immunoglobulins); hematologic; coagulation; and physiologic (blood loss, fluid
      and blood components received, weight gain, and duration of ventilation).
      Statistical analyses showed similar patient profiles in each group. Complement C4
      decreased in all groups postoperatively, but significantly less in the
      indomethacin group ( p < 0.01). Ketoconazole reduced postoperative bleeding ( p <
      0.0001) as well as the incidence of re-operation for bleeding ( p = 0.05). It was
      concluded that indomethacin decreases complement (specifically C4) consumption
      during cardiopulmonary bypass, and ketoconazole may reduce postoperative bleeding
      by limiting coagulation abnormalities in cardiac surgery patients.

PMID- 17540992
TI  - Minimally invasive aortic valve replacement in left ventricular dysfunction.
AB  - The safety and benefit of minimally invasive aortic valve replacement in patients
      with left ventricular dysfunction has not been well investigated. We conducted a
      retrospective review of 140 patients with ejection fraction <or= 40% who
      underwent isolated aortic valve replacement between July 1996 and March 2005.
      Aortic valve replacement was performed via an upper hemisternotomy in 73 patients
      and via a full sternotomy in 67. Two matched cohorts of 41 patients each were
      constructed using propensity score analysis, and the outcomes were compared.
      There was no significant difference in operative mortality (hemisternotomy, 2.4%
      vs 4.8% for full sternotomy), incidence of postoperative complications, blood
      transfusion requirement, length of hospital stay, or discharge to home rates.
      Aortic valve replacement via an upper hemisternotomy can be performed safely,
      even in patients with left ventricular dysfunction, with morbidity and mortality
      outcomes similar to those of a full sternotomy.

PMID- 17540993
TI  - Thromboendarterectomy for severe chronic thromboembolic pulmonary hypertension.
AB  - Pulmonary thromboendarterectomy is a curative surgical procedure for chronic
      thromboembolic pulmonary hypertension. The aim of this study was to clarify
      whether severe hemodynamic compromise affects surgical outcome. We studied 19
      patients who underwent pulmonary thromboendarterectomy and compared 11 with
      pulmonary vascular resistance < 1,000 dyne x s x cm(-5) (group 1) and 8 with
      pulmonary vascular resistance > 1,000 dyne x s x cm(-5) (group 2). Mean pulmonary
      artery pressure and pulmonary vascular resistance decreased significantly after
      surgery in both groups. The incidence of postoperative complications did not
      differ between groups; however, one patient in group 2 died of multiorgan
      failure. The overall mortality rate was 5.3%, and the rate in group 2 was 13%.
      Our results indicate that preoperative hemodynamic compromise does not affect
      surgical outcome. Patients with high pulmonary vascular resistance can be treated
      effectively by thromboendarterectomy, with acceptable morbidity and mortality.

PMID- 17540994
TI  - Endothoracic papaverine application for internal thoracic artery harvest.
AB  - This study compared the effects of different methods of papaverine application on
      free blood flow and harvesting time of the internal thoracic artery for coronary
      bypass grafting. Patients were randomly divided into 3 groups of 25 each: group 1
      had papaverine injected into the endothoracic tissue around the internal thoracic
      artery before dissection, group 2 had papaverine injected into the periarterial
      tissues of the internal thoracic artery pedicle, and group 3 had intraluminal
      papaverine applied retrogradely into the internal thoracic artery. Mean blood
      flow was 56.3 +/- 21.3, 21.1 +/- 13.2, and 20.9 +/- 9.1 mL x min(-1) in groups 1,
      2, and 3, respectively, immediately after harvesting. Flow in group 1 was
      significantly better than that in groups 2 and 3. Immediately before anastomosis,
      mean flow was 89.8 +/- 19.1, 97.6 +/- 35.4, and 95.9 +/- 19.9 mL x min(-1) in
      groups 1, 2, and 3, respectively, with no significant difference among groups.
      Internal thoracic artery harvesting times were shorter in group 1 than in groups
      2 and 3. Administering papaverine into the endothoracic fascia of the internal
      thoracic artery bed prior to dissection is a reliable method that facilitates
      rapid harvesting of the graft without causing trauma and consequent spasm.

PMID- 17540995
TI  - Definitive management of advanced empyema by two-window video-assisted surgery.
AB  - We describe how 2-window video-assisted thoracoscopic decortication and lung
      mobilization can provide definitive management of stage III empyema. This
      technique was used in 52 patients with stage III empyema. None required
      additional ports or a thoracotomy. Three patients (6%) needed computed tomography
      guided drainage of persistent large loculi, but none required further surgery.
      Chest radiographs at 6 weeks after surgery confirmed full lung expansion and
      resolution of pleural collection in the other 49 patients (94%).

PMID- 17540996
TI  - Repair of anomalous origin of left coronary artery from the pulmonary artery.
AB  - Patients with anomalous origin of the left coronary artery from the pulmonary
      artery often have mitral valve regurgitation. Although establishing dual coronary
      circulation is the procedure of choice, there remains controversy as to how the
      mitral valve is handled. Between April 1999 and August 2005, 8 patients underwent
      surgical correction at our institution. There were 4 males and 4 females, aged
      from 9 months to 13 years (mean, 6.4 years). Six patients underwent direct aortic
      reimplantation and 2 had a Takeuchi procedure. Simultaneous mitral annuloplasty
      was performed in 7 patients with moderate or severe mitral regurgitation. There
      were no deaths or postoperative complications. Follow-up ranged from 4 to 80
      months (mean, 34 +/- 26 months). Left ventricular function improved significantly
      from a preoperative fractional shortening of 0.21 +/- 0.09 to 0.35 +/- 0.06.
      Mitral regurgitation decreased on follow-up in the 7 patients who had mitral
      annuloplasty. We recommend performing mitral annuloplasty at the time of
      operation in patients with moderate or severe mitral regurgitation and anomalous
      origin of the left coronary artery from the pulmonary artery.

PMID- 17540997
TI  - Successful mechanical circulatory support as a bridge to transplantation.
AB  - With the progression of congestive heart failure, therapeutic options become
      fewer, and cardiac transplantation is the final option. The use of a left
      ventricular assist device improves the survival rate and quality of life in
      patients on the waiting list for transplantation. A 64-year-old man was
      successfully maintained on mechanical circulatory support with a left ventricular
      assist device for 502 days, as a bridge to transplantation.

PMID- 17540998
TI  - Lupus anticoagulant and off-pump coronary bypass: dilemma of anticoagulation.
AB  - Confronted with a persistently elevated activated partial thromboplastin time due
      to circulating lupus anticoagulant in a patient undergoing emergency off-pump
      coronary artery bypass surgery, the dilemma of providing adequate anticoagulation
      for a short cardiac surgical procedure is highlighted.

PMID- 17540999
TI  - Diaphragmatic laceration, partial liver herniation and catamenial pneumothorax.
AB  - Catamenial pneumothorax is a recurrent pneumothorax temporally associated with
      menstruation. Pathogenesis remains debated however pleural endometriosis or
      diaphragmatic abnormalities are almost always present. We report the case of a 35
      year-old woman with recurrent right catamenial pneumothorax. At thoracoscopy a
      large laceration of the diaphragm with partial intrathoracic liver herniation was
      seen. Treatment involved repair of the diaphragmatic lacerations, and
      pleurodesis. This report shows that large diaphragmatic defects may be observed
      in patients with catamenial pneumothorax.

PMID- 17541000
TI  - High-risk repair of ascending aortic aneurysm due to giant cell aortitis.
AB  - Giant cell arteritis increases the risk of developing a thoracic aortic aneurysm.
      Thoracic aortic aneurysm repair in octogenarians carries a profound increase in
      postoperative morbidity and mortality. We report the successful repair of an
      ascending aortic aneurysm in an 83-year-old woman with a history of treatment for
      temporal arteritis and pathologic evidence of giant cell aortitis.

PMID- 17541001
TI  - Coincidence of spinal canal stenosis and thoracoabdominal aortic aneurysm.
AB  - We report a case in which a thoracoabdominal aneurysm was present in association
      with previously unknown critical spinal canal stenosis. In spite of using left
      heart bypass, systemic hypothermia, and controlled cerebrospinal fluid drainage
      for spinal cord protection, the patient developed paraplegia following aortic
      aneurysm repair. Computed tomography scan revealed critical stenosis of the
      spinal canal that was thought to be sufficient to produce spinal cord compression
      syndromes including paraplegia.

PMID- 17541002
TI  - Mitral valve repair in infants and children.
AB  - A number of children are born with myxomatous deformity of the mitral valve,
      causing mitral regurgitation. Traditional techniques of repair may be daunting in
      these children because apart from their small size, their valves appear grossly
      deformed and the tissues are friable. Techniques to circumvent these problems and
      ensure a predictable and satisfactory outcome are described.

PMID- 17541003
TI  - Modified sandwich technique for acute aortic dissection.
AB  - We describe a new method for aortic anastomosis in the repair of acute type A
      aortic dissection. The anastomosis site is prepared with the adventitial
      inversion technique, which converts a dissected aorta into a conduit lined with
      tough adventitia. The end is reinforced with felt strip outside and anastomosed
      with interrupted everting mattress and running sutures, resulting in complete
      hemostasis. This modified sandwich technique will likely be useful for the
      surgical treatment of acute aortic dissection.

PMID- 17541004
TI  - Myocardial revascularization: surgery or stenting?
AB  - There is current debate regarding the relative merits and roles of surgical
      revascularization and percutaneous revascularization for patients with
      obstructive coronary artery disease. This article reviews the current literature
      relating to this subject.

PMID- 17541005
TI  - Coarctation of aorta with intercostal artery aneurysm and patent ductus
      arteriosus.

PMID- 17541006
TI  - Giant localized fibrous tumor of the pleura.

PMID- 17541007
TI  - Intracardiac migration of a Kirschner wire from the right clavicle.

PMID- 17541008
TI  - Multi-slice scanner in transdiaphragmatic coronary and abdominal aortic surgery.

PMID- 17541009
TI  - Molecular multitasking in the airspace: alpha1-antitrypsin takes on thrombin and
      plasmin.

PMID- 17541010
TI  - Post-infection A77-1726 blocks pathophysiologic sequelae of respiratory syncytial
      virus infection.
AB  - Despite respiratory syncytial virus (RSV) bronchiolitis remaining the most common
      cause of lower respiratory tract disease in infants worldwide, treatment has
      progressed little in the past 30 years. The aim of our study was to determine
      whether post-infection administration of de novo pyrimidine synthesis inhibitors
      could prevent the reduction in alveolar fluid clearance (AFC) and hypoxemia that
      occurs at Day 2 after intranasal infection of BALB/c mice with RSV. BALB/c mice
      were infected intranasally with RSV strain A2. AFC was measured in anesthetized,
      ventilated mice after instillation of 5% bovine serum albumin into the dependent
      lung. Post-infection systemic treatment with leflunomide has no effect on AFC.
      However, when added to the AFC instillate, leflunomide's active metabolite, A77
      1726, blocks RSV-mediated inhibition of AFC at Day 2. This block is reversed by
      uridine (which allows pyrimidine synthesis via the scavenger pathway) and not
      recapitulated by genistein (which mimics the tyrosine kinase inhibitor effects of
      A77-1726), indicating that the effect is specific for the de novo pyrimidine
      synthesis pathway. More importantly, when administered intranasally at Day 1, A77
      1726, but not its vehicle dimethyl sulfoxide, maintains its beneficial effect on
      AFC and lung water content until Day 2. Intranasal instillation of A77-1726 at
      Day 1 also reduces bronchoalveolar lavage nucleotide levels, lung inflammation,
      and hypoxemia at Day 2 without impairing viral replication at Day 2 or viral
      clearance at Day 8. Post-infection intranasal or aerosolized treatment with
      pyrimidine synthesis inhibitors may provide symptomatic relief from the
      pathophysiologic sequelae of impaired AFC in children with RSV bronchiolitis.

PMID- 17541011
TI  - IL-13 regulates cilia loss and foxj1 expression in human airway epithelium.
AB  - Mucociliary clearance is essential to the defense mechanisms of the respiratory
      system. Loss of normal mucociliary clearance contributes to the pathogenesis of
      genetic and acquired lung diseases. Treatment of cultured differentiated human
      airway epithelial tissue with IL-13 resulted in a loss of ciliated epithelial
      cells and an increase in mucus-secreting cells. The loss of ciliated cells was
      characterized by mislocation of basal bodies and loss of ezrin from the apical
      cell compartment. In addition to the loss of ciliated cells and increase in
      mucous cells after IL-13 treatment, cells with characteristics of both ciliated
      and mucous cells were observed in the airway epithelium. In association with the
      decrease in ciliated cells after IL-13 treatment, there was noted a decrease in
      foxj1 expression in the airway epithelium, characterized by a decrease in the
      number of foxj1-expressing cells. Within the foxj1 promoter, a STAT-binding
      element was identified and inhibition of foxj1 expression by STAT-6 and IL-13 was
      demonstrated. These findings suggest molecular and cellular mechanisms for cilia
      loss in pulmonary disease. Inhibition of foxj1 expression results in loss of
      apical localization of ezrin and basal bodies with subsequent loss of axonemal
      structures. These findings have important implications for the pathogenesis and
      treatment of airway diseases.

PMID- 17541012
TI  - Embryonic essential myosin light chain regulates fetal lung development in rats.
AB  - Congenital diaphragmatic hernia (CDH) is currently the most life-threatening
      congenital anomaly the major finding of which is lung hypoplasia. Lung hypoplasia
      pathophysiology involves early developmental molecular insult in branching
      morphogenesis and a late mechanical insult by abdominal herniation in maturation
      and differentiation processes. Since early determinants of lung hypoplasia might
      appear as promising targets for prenatal therapy, proteomics analysis of normal
      and nitrofen-induced hypoplastic lungs was performed at 17.5 days after
      conception. The major differentially expressed protein was identified by mass
      spectrometry as myosin light chain 1a (MLC1a). Embryonic essential MLC1a and
      regulatory myosin light chain 2 (MLC2) were characterized throughout normal and
      abnormal lung development by immunohistochemistry and Western blot. Disruption of
      MLC1a expression was assessed in normal lung explant cultures by antisense
      oligodeoxynucleotides. Since early stages of normal lung development, MLC1a was
      expressed in vascular smooth muscle (VSM) cells of pulmonary artery, and MLC2 was
      present in parabronchial smooth muscle and VSM cells of pulmonary vessels. In
      addition, early smooth muscle differentiation delay was observed by
      immunohistochemistry of alpha-smooth muscle actin and transforming growth factor
      beta1. Disruption of MLC1a expression during normal pulmonary development led to
      significant growth and branching impairment, suggesting a role in branching
      morphogenesis. Both MLC1a and MLC2 were absent from hypoplastic fetal lungs
      during pseudoglandular stage of lung development, whereas their expression
      partially recovered by prenatal treatment with vitamin A. Thus, a deficiency in
      contractile proteins MLC1a and MLC2 might have a role among the early molecular
      determinants of lung hypoplasia in the rat model of nitrofen-induced CDH.

PMID- 17541013
TI  - Akt-mediated activation of HIF-1 in pulmonary vascular endothelial cells by S
      nitrosoglutathione.
AB  - S-nitrosoglutathione (GSNO) stabilizes the alpha-subunit of hypoxia inducible
      factor-1 (HIF-1) in normoxic cells, but not in the presence of PI3K inhibitors.
      In this report, the biochemical pathway by which GSNO alters PI3K/Akt activity to
      modify HIF-1 expression was characterized in Cos cells and primary pulmonary
      vascular endothelial cells. GSNO increased Akt kinase activity--and downstream
      HIF-1alpha protein accumulation and DNA-binding activity--in a dose- and time
      dependent manner. The PI3K inhibitors, wortmannin and LY294002, blocked these
      responses. Neither glutathione nor 8-bromo-cyclic GMP mimicked the GSNO-induced
      increases in Akt kinase activity. GSNO-induced Akt kinase activity and downstream
      HIF-1alpha stabilization were blocked by acivicin, an inhibitor of gamma-glutamyl
      transpeptidase (gammaGT), a transmembrane protein that can translate
      extracellular GSNO to intracellular S-nitrosocysteinylglycine. Dithiothreitol
      blocked GSNO-induced Akt kinase activity and HIF-1alpha stabilization. Moreover,
      the 3'-phosphatase of phosphoinositides, PTEN (phosphatase and tensin homolog
      deleted on chromosome ten) was S-nitrosylated by GSNO in pulmonary arterial
      endothelial cells, which was reversed by dithiothreitol and ultraviolet light.
      Interestingly, the abundance of S-nitrosylated PTEN also correlated inversely
      with PTEN activity. Taken together, these results suggest that GSNO induction of
      Akt appears to be mediated by S-nitrosylation chemistry rather than classic NO
      signaling through guanylate cyclase/cGMP. We speculate that gammaGT-dependent
      activation of Akt and subsequent activation of HIF-1 in vascular beds may be
      relevant to the regulation of HIF-1-dependent gene expression in conditions
      associated with oxyhemoglobin deoxygenation, as opposed to profoundly low Po(2),
      in the pulmonary vasculature.

PMID- 17541014
TI  - Restoration of W1282X CFTR activity by enhanced expression.
AB  - Cystic fibrosis results from mutations in the cystic fibrosis transmembrane
      conductance regulator (CFTR) gene. Premature termination codons represent a
      common minority of CFTR mutations, and are caused by base pair substitutions that
      produce abnormal stop codons in the coding sequence. Select aminoglycosides
      induce "translational readthrough" of premature stop codons and have been shown
      to restore full-length functional protein in a number of preclinical and clinical
      settings. We studied two well-described premature termination codons found in the
      distal open reading frame of CFTR, W1282X and R1162X, expressed in polarizing and
      nonpolarizing cells. Our findings indicate that W1282X CFTR-expressing cells
      demonstrate significantly greater CFTR activity when overexpressed compared with
      R1162X CFTR cells, even when truncated protein is the predominant form. In
      addition, our results show that the combination of stimulated expression and stop
      codon suppression produces additive effects on CFTR-mediated ion transport. These
      findings provide evidence that W1282X CFTR exhibits membrane localization and
      retained chloride channel function after enhanced expression, and suggest that
      patients harboring this mutation may be more susceptible to CFTR rescue.

PMID- 17541015
TI  - Bronchiolitis obliterans syndrome in chemical workers producing diacetyl for food
      flavorings.
AB  - RATIONALE: Workers in microwave popcorn plants are at risk of developing
      bronchiolitis obliterans associated with exposure to butter flavoring volatiles,
      including diacetyl. OBJECTIVES: To investigate the risk of bronchiolitis
      obliterans for chemical workers producing diacetyl, with exposure to less complex
      mixtures of chemicals. METHODS: We interviewed and conducted spirometry on 175 of
      196 workers from a chemical production plant that produced diacetyl between 1960
      and 2003. We used all available historical exposure data to classify all workers
      into three exposure groups with varying exposure profiles to diacetyl, based on
      frequency and level of exposure. MEASUREMENTS AND MAIN RESULTS: Workers with
      fixed airway obstruction underwent further pulmonary function testing (including
      diffusing capacity and lung volumes) and paired inspiratory and expiratory high
      resolution computed tomography studies. We identified three cases consistent with
      bronchiolitis obliterans syndrome with air trapping on high-resolution computed
      tomography of the lungs, in the highest exposure group of 102 process operators.
      Two of these cases were lifelong nonsmokers. Potential exposures included
      acetoin, diacetyl, acetaldehyde, and acetic acid, with diacetyl exposures in the
      range previously reported to be associated with fixed airway obstruction in the
      microwave popcorn industry. CONCLUSIONS: Exposure to an agent during diacetyl
      production appears to be responsible for causing bronchiolitis obliterans
      syndrome in chemical process operators, consistent with the suspected role of
      diacetyl in downstream food production.

PMID- 17541016
TI  - Plasminogen is an important regulator in the pathogenesis of a murine model of
      asthma.
AB  - RATIONALE: Asthma is a syndrome whose common pathogenic expression is
      inflammation of the airways. Plasminogen plays an important role in cell
      migration and is also implicated in tissue remodeling, but its role in asthma has
      not been defined. OBJECTIVES: To test whether plasminogen is a critical component
      in the development of asthma. METHODS: We used a mouse model of ovalbumin-induced
      pulmonary inflammation in Plg(+/+), Plg(+/-), and Plg(-/-) mice. MEASUREMENTS AND
      MAIN RESULTS: The host responses measured included lung morphometry, and
      inflammatory mediators and cell counts were assessed in bronchoalveolar lavage
      fluid. Bronchoalveolar lavage demonstrated a marked increase in eosinophils and
      lymphocytes in ovalbumin-treated Plg(+/+) mice, which were reduced to phosphate
      buffered saline-treated control levels in Plg(+/-) or Plg(-/-) mice. Lung
      histology revealed peribronchial and perivascular leukocytosis, mucus production,
      and increased collagen deposition in ovalbumin-treated Plg(+/+) but not in Plg(+/
      ) or Plg(-/-) mice. IL-5, tumor necrosis factor-alpha, and gelatinases, known
      mediators of asthma, were detected in bronchoalveolar lavage fluid of ovalbumin
      treated Plg(+/+) mice, yet were reduced in Plg(-/-) mice. Administration of the
      plasminogen inhibitor, tranexamic acid, reduced eosinophil and lymphocyte
      numbers, mucus production, and collagen deposition in the lungs of ovalbumin
      treated Plg(+/+) mice. CONCLUSIONS: The decreased inflammation in the lungs of
      Plg(-/-) mice and its blockade with a plasminogen inhibitor indicate that
      plasminogen plays an important role in orchestrating the asthmatic response and
      suggests that plasminogen may be a therapeutic target for the treatment of
      asthma.

PMID- 17541017
TI  - Association between metabolic syndrome and sleep-disordered breathing in
      adolescents.
AB  - RATIONALE: Metabolic syndrome (MetS) affects 4 to 10% of adolescents. Risk
      factors include overweight, male sex, and Hispanic ethnicity. Although sleep
      disordered breathing (SDB) has been implicated as a risk factor for MetS in
      adults, its association with SDB in adolescents is unknown. OBJECTIVES: To define
      the association of SDB with MetS in adolescents. METHODS: Standardized
      measurements of SDB, anthropometry and bioassays, were made in 270 adolescents,
      aged 13.6 +/- 0.7 years. MetS was identified if threshold levels were exceeded in
      three of five areas: waist circumference, blood pressure, triglyceride level,
      high-density lipoprotein cholesterol level, and glucose levels. MEASUREMENTS AND
      MAIN RESULTS: Although 70% of children with SDB (apnea-hypopnea index >or= 5)
      were overweight and 59% had MetS, 16% of children without SDB had MetS. Twenty
      five percent of those with MetS had SDB. After adjusting for age, race, sex, and
      preterm status, children with SDB had a 6.49 (95% confidence interval, 2.52,
      16.70) increased odds of MetS compared with children without SDB. Indices of SDB
      stress associated with MetS included respiratory event frequency, degree of
      oxygen desaturation, and sleep efficiency. Analyses of individual metabolic
      parameters showed that, after adjustment for body mass index, SDB was associated
      with systolic and diastolic blood pressure, low-density lipoprotein cholesterol,
      and fasting insulin levels. CONCLUSIONS: A majority of adolescents with SDB are
      overweight and meet criteria for MetS. The close association between MetS and SDB
      and their putative interacting pathophysiologies suggests a need to develop
      screening, prevention, and treatment strategies for both disorders in high-risk,
      overweight adolescents.

PMID- 17541018
TI  - Regulatory T cells depress immune responses to protective antigens in active
      tuberculosis.
AB  - RATIONALE: Tuberculosis (TB) remains a leading cause of death, and the role of T
      cell responses to control Mycobacterium tuberculosis infections is well
      recognized. Patients with latent TB infection develop strong IFN-gamma responses
      to the protective antigen heparin-binding hemagglutinin (HBHA), whereas patients
      with active TB do not. OBJECTIVES: We investigated the mechanism of this
      difference and evaluated the possible involvement of regulatory T (Treg) cells
      and/or cytokines in the low HBHA T-cell responses of patients with active TB.
      METHODS: The impact of anti-transforming growth factor (TGF)-beta and anti-IL-10
      antibodies and of Treg cell depletion on the HBHA-induced IFN-gamma secretion was
      analyzed, and the Treg cell phenotype was characterized by flow cytometry.
      MEASUREMENTS AND MAIN RESULTS: Although the addition of anti-TGF-beta or anti-IL
      10 antibodies had no effect on the HBHA-induced IFN-gamma secretion in patients
      with active TB, depletion of CD4(+)CD25(high)FOXP3(+) T lymphocytes resulted in
      the induction by HBHA of IFN-gamma concentrations that reached levels similar to
      those obtained for latent TB infection. No effect was noted on the early-secreted
      antigen target-6 or candidin T-cell responses. CONCLUSIONS: Specific
      CD4(+)CD25(high)FOXP3(+) T cells depress the T-cell-mediated immune responses to
      the protective mycobacterial antigen HBHA during active TB in humans.

PMID- 17541019
TI  - Mechanical stretch simulates proliferation of venous smooth muscle cells through
      activation of the insulin-like growth factor-1 receptor.
AB  - OBJECTIVE: Activation and proliferation of vascular smooth muscle cells (VSMCs)
      occur in the venous neointima of vein grafts. VSMCs in a grafted vein are
      subjected to mechanical stretch; our goal is to understand the essential
      mechanical stretch-regulated signals that influence VSMCs during neointimal
      formation in vein grafts. METHODS AND RESULTS: In cultured vein VSMCs, mechanical
      stretch induces proliferation and upregulation of both IGF-1 and IGF-1R. Stretch
      of VSMCs sustained tyrosine phosphorylation of both IGF-1R and its substrate, IRS
      1; these responses were related to mechanical stretch-induced activation of Src
      and autocrine IGF-1 production. Mechanical stretch-activated IGF-1R is functional
      because there is a prolonged activation of IRS-1-associated phosphatidylinositol
      3 kinase (PI3K). When we knocked out IGF-1R, the mechanical stretch-induced
      increase in VSMC proliferation was blocked. To link mechanical stretch-activated
      IGF-1R cell signaling to venous VSMC proliferation in vivo, we also studied a
      vein graft model. Tamoxifen-inducible null deletion of IGF-1R in mice reduced the
      formation of neointima in the vein graft. CONCLUSIONS: Our results demonstrate
      for the first time that mechanical stretch activates IGF-1/IGF-1R signals in
      venous VSMCs, and we have uncovered a signaling pathway that leads to neointima
      formation in vivo.

PMID- 17541020
TI  - In vivo reverse cholesterol transport from macrophages lacking ABCA1 expression
      is impaired.
AB  - BACKGROUND: ATP-binding cassette transporter A1 (ABCA1) is a key mediator of
      cholesterol efflux to apoA-I in cholesterol loaded macrophages, a first step of
      reverse cholesterol transport (RCT) in vivo. Macrophage specific abca1
      inactivation or overexpression, respectively, accelerated or suppressed the
      development of atherosclerosis in mouse models. However, it is yet to be
      established that the ABCA1 effect is related to specific changes in RCT from the
      macrophages in vivo. METHODS AND RESULTS: one marrow-derived macrophages from
      abca1-/- or abca1+/- mice were labeled with 3H-cholesterol-AcLDL or 3H
      cholesterol-LDL and injected into abca1+/+ abca1+/- or abca1-/- mice. When
      injected into abca1+/+ mice, return of 3H-cholesterol from labeled abca1-/-
      macrophages to serum, liver, bile, and feces was reduced by 50% (P=0.01) compared
      with control. When labeled wild-type macrophages were injected into abca1-/-
      mice, as compared with wild-type mice, the return of 3H-cholesterol to serum,
      liver, bile, and feces was also reduced. CONCLUSIONS: ABCA1 expression in
      macrophages contributes significantly to in vivo macrophage RCT. The important
      residual RCT observed from abca1-/- macrophages highlight the functionality of
      transporters that efflux to HDL.

PMID- 17541021
TI  - Relationship between a systemic inflammatory marker, plaque inflammation, and
      plaque characteristics determined by intravascular optical coherence tomography.
AB  - OBJECTIVE: The purpose of this study was to evaluate the relationships between
      the peripheral white blood cell (WBC) count, local plaque fibrous cap macrophage
      density, and the morphological features and presence of thin-cap fibroatheromas
      (TCFA) identified by optical coherence tomography (OCT). METHODS AND RESULTS: OCT
      was performed in patients undergoing catheterization. Images were analyzed using
      validated criteria for plaque characteristics. Baseline WBC count correlated with
      macrophage density (r=0.483, P<0.001). Both parameters were associated with lipid
      rich plaque and correlated inversely with plaque fibrous cap thickness (r=-0.547
      for macrophage density and -0.423 for WBC count, P<0.015). Plaques classified as
      TCFA had a higher median macrophage density than non-TCFA plaques (7.4 versus
      4.99, P<0.001). Patients with TCFA had a higher WBC count compared with those
      without TCFA (11.0 versus 7.9, P=0.007). Receiver operator curves for WBC count,
      macrophage density, and these combined parameters for prediction of TCFA showed
      the area under the curves were 0.88, 0.91, and 0.97 (P<0.001), respectively.
      CONCLUSION: This study provides the first in vivo data linking the peripheral WBC
      count, plaque fibrous cap macrophage density, and the characteristics and
      presence of TCFA. Macrophage density correlated with the WBC count, and both
      parameters independently and particularly in combination predict the presence of
      TCFA.

PMID- 17541022
TI  - Oxidized phospholipids, lipoprotein(a), lipoprotein-associated phospholipase A2
      activity, and 10-year cardiovascular outcomes: prospective results from the
      Bruneck study.
AB  - BACKGROUND: Oxidized phospholipids (OxPL) circulate on apolipoprotein B-100
      particles (OxPL/apoB), and primarily on Lp(a) lipoprotein (a) [Lp(a)]. The
      relationship of OxPL/apoB levels to future cardiovascular events is not known.
      METHODS AND RESULTS: The Bruneck study is a prospective population-based survey
      of 40- to 79-year-old men and women recruited in 1990. Plasma levels of OxPL/apoB
      and lipoprotein (a) [Lp(a)] were measured in 765 subjects in 1995 and incident
      cardiovascular disease (CVD), defined as cardiovascular death, myocardial
      infarction, stroke, and transient ischemic attack, was assessed from 1995 to
      2005. During the follow-up period, 82 subjects developed CVD. In multivariable
      analysis, which included traditional risk factors, high sensitivity C-reactive
      protein (hsCRP), and lipoprotein-associated phospholipase A2 (Lp-PLA2) activity,
      subjects in the highest tertile of OxPL/apoB had a significantly higher risk of
      cardiovascular events than those in the lowest tertile (hazard ratio[95% CI]
      2.4[1.3 to 4.3], P=0.004). The strength of the association between OxPL/apoB and
      CVD risk was amplified with increasing Lp-PLA2 activity (P=0.018 for
      interaction). Moreover, OxPL/apoB levels predicted future cardiovascular events
      beyond the information provided by the Framingham Risk Score (FRS). The effects
      of OxPL/apoB and Lp(a) were not independent of each other but they were
      independent of all other measured risk factors. CONCLUSIONS: This study
      demonstrates that OxPL/apoB levels predict 10-year CVD event rates independently
      of traditional risk factors, hsCRP, and FRS. Increasing Lp-PLA2 activity further
      amplifies the risk of CVD mediated by OxPL/apoB.

PMID- 17541023
TI  - Age moderates the short-term effects of transdermal 17beta-estradiol on
      endothelium-dependent vascular function in postmenopausal women.
AB  - OBJECTIVE: We evaluated age and coronary heart disease (CHD) as potential
      moderators of the effects of 17beta-estradiol on vascular endothelial function in
      postmenopausal women. METHODS AND RESULTS: In a double-blind crossover design,
      100 postmenopausal women aged 50 to 80 years were randomized to each of 3
      transdermal patches, releasing 17beta-estradiol (0.05 mg/d), 17beta-estradiol
      (0.05 mg/d) + norethindrone acetate (NETA, 0.14 mg/d), and placebo. Flow-mediated
      dilation (FMD) and response to 400 microg sublingual glyceryl trinitrate (GTN-D)
      were assessed approximately 18 hours after patch placement. Age, but not CHD,
      moderated the FMD response to treatment (P=0.01). For women in their fifties, the
      estradiol patch was associated with improved FMD (7.69+/-4.79%) compared with
      placebo (4.81+/-5.97%, P<0.05), but the estradiol+norethindrone patch response
      (5.81+/-4.85%) was not significantly different from placebo. Women in their
      sixties and seventies showed no alterations in FMD response to either active
      patch. GTN-D response declined with advancing age (P<0.01), with women in their
      seventies exhibiting blunted GTN-D response compared with younger women.
      CONCLUSIONS: The cardiovascular benefits of natural estrogen supplementation on
      vascular endothelial function may be dependent on postmenopausal age, with
      improved vascular function evident only in the early postmenopausal years. Short
      term FMD response to estradiol might help stratify individual differences in
      risks versus benefits of HRT.

PMID- 17541024
TI  - Peripheral circadian clocks in the vasculature.
AB  - Living organisms have adapted to the daily rotation of the earth and regular
      changes in the light environment. Life forms anticipate environmental
      transitions, adapt their own physiology, and perform activities at behaviorally
      advantageous times during the day. This is achieved by means of endogenous
      circadian clocks that can be synchronized to the daily changes in external cues,
      most notably light and temperature. For many years it was thought that neurons of
      the suprachiasmatic nucleus (SCN) uniquely controlled circadian rhythmicity of
      peripheral tissues via neural and humoral signals. The cloning and
      characterization of mammalian clock genes revealed that they are expressed in a
      circadian manner throughout the body. It is now accepted that peripheral cells,
      including those of the cardiovascular system, contain a circadian clock similar
      to that in the SCN. Many aspects of cardiovascular physiology are subject to
      diurnal variation, and serious adverse cardiovascular events including myocardial
      infarction, sudden cardiac death, and stroke occur with a frequency conditioned
      by time of day. This has raised the possibility that biological responses under
      the control of the molecular clock might interact with environmental cues to
      influence the phenotype of human cardiovascular disease.

PMID- 17541025
TI  - Heme oxygenase-1: a novel key player in the development of tolerance in response
      to organic nitrates.
AB  - OBJECTIVE: Nitrate tolerance is likely attributable to an increased production of
      reactive oxygen species (ROS) leading to an inhibition of the mitochondrial
      aldehyde dehydrogenase (ALDH-2), representing the nitroglycerin (GTN) and
      pentaerythrityl tetranitrate (PETN) bioactivating enzyme, and to impaired nitric
      oxide bioactivity and signaling. We tested whether differences in their capacity
      to induce heme oxygenase-1 (HO-1) might explain why PETN and not GTN therapy is
      devoid of nitrate and cross-tolerance. METHODS AND RESULTS: Wistar rats were
      treated with PETN or GTN (10.5 or 6.6 microg/kg/min for 4 days). In contrast to
      GTN, PETN did not induce nitrate tolerance or cross-tolerance as assessed by
      isometric tension recordings in isolated aortic rings. Vascular protein and mRNA
      expression of HO-1 and ferritin were increased in response to PETN but not GTN.
      In contrast to GTN therapy, NO signaling, ROS formation, and the activity of ALDH
      2 (as assessed by an high-performance liquid chromatography-based method) were
      not significantly influenced by PETN. Inhibition of HO-1 expression by apigenin
      induced "tolerance" to PETN whereas HO-1 gene induction by hemin prevented
      tolerance in GTN treated rats. CONCLUSIONS: HO-1 expression and activity appear
      to play a key role in the development of nitrate tolerance and might represent an
      intrinsic antioxidative mechanism of therapeutic interest.

PMID- 17541026
TI  - Nitric oxide in the pulmonary vasculature.
AB  - Homeostasis in the pulmonary vasculature is maintained by the actions of
      vasoactive compounds, including nitric oxide (NO). NO is critical for normal
      development of the pulmonary vasculature and continues to mediate normal
      vasoregulation in adulthood. Loss of NO bioavailability is one component of the
      endothelial dysfunction and vascular pathology found in pulmonary hypertension
      (PH). A broad research effort continues to expand our understanding of the
      control of NO production and NO signaling and has generated novel theories on the
      importance of pulmonary NO production in the control of the systemic vasculature.
      This understanding has led to exciting developments in our ability to treat PH,
      including inhaled NO and phosphodiesterase inhibitors, and to several promising
      directions for future therapies using nitric oxide-donor compounds, stimulators
      of soluble guanylate cyclase, progenitor cells expressing NO synthase (NOS), and
      NOS gene manipulation.

PMID- 17541027
TI  - Mouse models for atherosclerosis and pharmaceutical modifiers.
AB  - Atherosclerosis is a multifactorial highly-complex disease with numerous
      etiologies that work synergistically to promote lesion development. The ability
      to develop preventive and ameliorative treatments will depend on animal models
      that mimic the human subject metabolically and pathophysiologically and will
      develop lesions comparable to those in humans. The mouse is the most useful,
      economic, and valid model for studying atherosclerosis and exploring effective
      therapeutic approaches. Among the most widely used mouse models for
      atherosclerosis are apolipoprotein E-deficient (ApoE-/-) and LDL receptor
      deficient (LDLr-/-) mice. An up-and-coming model is the ApoE*3Leiden (E3L)
      transgenic mouse. Here, we review studies that have explored how and to what
      extent these mice respond to compounds directed at treatment of the risk factors
      hypercholesterolemia, hypertriglyceridemia, hypertension, and inflammation. An
      important outcome of this survey is that the different models used may differ
      markedly from one another in their response to a specific experimental
      manipulation. The choice of a model is therefore of critical importance and
      should take into account the risk factor to be studied and the working spectrum
      of the compounds tested.

PMID- 17541028
TI  - Nox1 mediates basic fibroblast growth factor-induced migration of vascular smooth
      muscle cells.
AB  - OBJECTIVE: Basic fibroblast growth factor (bFGF) stimulates vascular smooth
      muscle cell (SMC) migration. We determined whether bFGF increases SMC reactive
      oxygen-species (ROS) and studied the role of ROS for SMC migration. METHODS AND
      RESULTS: bFGF rapidly increased rat SMC ROS formation and migration through
      pathways sensitive to inhibition of NADPH oxidases, PI3-kinase, protein kinase C,
      and Rac-1. SiRNA directed against the NADPH oxidase Nox4 impaired basal but not
      bFGF-induced ROS formation and did not affect migration. In contrast, siRNA
      against Nox1 blocked the agonist-induced ROS generation as well as the bFGF
      induced migration. Agonist-induced migration was also attenuated in SMC derived
      from Nox1 y/- mice and transduction of Nox1 restored normal migration. Likewise,
      SMC outgrowth in response to bFGF was attenuated in aortic segments from Nox1 y/-
      mice as compared with Nox1 y/+ mice. bFGF activated JNK but not Src in a Nox1
      dependent manner. Consequently, phosphorylation of the adaptor protein paxillin,
      which is central for migration and secretion of matrix-metalloproteinases, were
      dependent on Nox1 as well as JNK but not Src. CONCLUSIONS: These data demonstrate
      that bFGF activates the Nox1-containing NADPH oxidase and that bFGF through a
      pathway involving ROS and JNK stimulates SMC migration.

PMID- 17541029
TI  - Vascular remodeling: hemodynamic and biochemical mechanisms underlying Glagov's
      phenomenon.
AB  - An important concept for vascular remodeling, termed Glagov's phenomenon, is that
      arteries remodel to maintain constant flow despite increases in atherosclerotic
      lesion mass. Although Glagov's phenomenon was originally described only for the
      case of arterial remodeling in response to growth of atherosclerotic plaques,
      experimental and clinical observations indicate that blood flow properties
      influence remodeling after angioplasty, hypertension, and flow diversion as well
      as atherosclerotic plaque progression. This review attempts to define Glagov's
      observation in terms of the physical parameters of blood in conduit arteries that
      must determine the remodeling response. Next we review experiments that have
      begun to identify specific molecules that influence vascular remodeling and
      therefore may serve as mediators for the phenomena. More comprehensive analyses
      of the specific molecular pathways in the vessels that determine constant flow
      may provide new therapeutic approaches to regulate vascular remodeling.

PMID- 17541030
TI  - Can untrained laypersons use a defibrillator with dispatcher assistance?
AB  - OBJECTIVES: Automated external defibrillators (AEDs) provide an opportunity to
      improve survival in out-of-hospital cardiac arrest by enabling laypersons not
      trained in rhythm recognition to deliver lifesaving therapy. This study was
      performed to examine whether untrained laypersons could safely and effectively
      use these AEDs with telephone-guided instructions and if this action would
      compromise the performance of cardiopulmonary resuscitation (CPR) during a
      simulated ventricular fibrillation out-of-hospital cardiac arrest. METHODS: Fifty
      four conscripts without previous medical education were recruited from the
      Western Command in Finland. For this study, the participants were divided at
      random to form teams of two persons. The teams were randomized to dispatcher
      assisted CPR with or without AED operation during a simulated ventricular
      fibrillation out-of-hospital cardiac arrest. The time interval from collapse to
      first shock, hands-off time, and the quality of CPR were compared between the two
      groups. RESULTS: The quality of CPR was poor in both groups. The use of an AED
      did not increase the hands-off time or the time interval to the first
      compression. Sixty-four percent of the teams in the AED group managed to give the
      first defibrillatory shock within 5 minutes. CONCLUSIONS: The quality of
      dispatcher-assisted CPR is poor. Dispatcher assistance in defibrillation by a
      layperson not trained to use an AED seems feasible and does not compromise the
      performance of CPR.

PMID- 17541031
TI  - Epithelial to mesenchymal transition predicts gefitinib resistance in cell lines
      of head and neck squamous cell carcinoma and non-small cell lung carcinoma.
AB  - The modest response of patients with head and neck squamous cell carcinoma
      (HNSCC) and non-small cell lung carcinoma (NSCLC) to epithelial growth factor
      receptor tyrosine kinase inhibitors such as gefitinib and erlotinib indicates the
      need for the development of biomarkers to predict response. We determined
      gefitinib sensitivity in a panel of HNSCC cell lines by a 5-day 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and confirmed these
      responses with analysis of downstream signaling by immunoblotting and cell cycle
      arrest. Basal gene expression profiles were then determined by microarray
      analysis and correlated with gefitinib response. These data were combined with
      previously reported NSCLC microarray results to generate a broader predictive
      index. Common markers of resistance between the two tumor types included genes
      associated with the epithelial to mesenchymal transition. We confirmed that
      increased protein expression of vimentin combined with the loss of E-cadherin,
      claudin 4, and claudin 7 by immunoblotting was associated with gefitinib
      resistance in both HNSCC and NSCLC cell lines. In addition, the loss of the
      Ca(2+)-independent cell-cell adhesion molecules EpCAM and TROP2 in resistant
      lines was confirmed by immunofluorescence. Tumor xenografts derived from the
      gefitinib-sensitive UM-SCC-2 were growth-delayed by gefitinib, whereas the
      gefitinib-resistant 1483 xenografts were unaffected. These data support a role
      for epithelial to mesenchymal transition in establishing gefitinib resistance for
      both HNSCC and NSCLC, and indicate that clinical trials should address whether
      these biomarkers will be useful for patient selection.

PMID- 17541032
TI  - Detection of myeloma in skeleton of mice by whole-body optical fluorescence
      imaging.
AB  - Development of new therapies for myeloma has been hindered by the lack of
      suitable preclinical animal models of the disease in which widespread tumor foci
      in the skeleton can be detected reliably. Traditional means of detecting skeletal
      tumor infiltration such as histopathology are cumbersome and labor-intensive and
      do not allow temporal monitoring of tumor progression or regression in response
      to therapy. To resolve this problem, we modified the Radl 5TGM1 model of myeloma
      bone disease such that fluorescent myeloma tumors can be optically imaged in
      situ. Here, we show that murine myeloma 5TGM1 tumor cells, engineered to express
      enhanced green fluorescent protein (eGFP; 5TGM1-eGFP cells), can be imaged in a
      temporal fashion using a fluorescence illuminator and a charge-coupled device
      camera in skeletons of live C57BL/KaLwRij mice. High-resolution, whole-body
      images of tumor-bearing mice revealed that myeloma cells homed almost exclusively
      to the skeleton, with multiple focal tumor foci in the axial skeleton, consistent
      with myeloma tumor distribution in humans. Finally, the tested antitumor
      treatment effect of Velcade (bortezomib), a proteasome inhibitor used clinically
      in myeloma, was readily detected by GFP imaging, suggesting the power of the
      technique in combination with the Radl 5TGM1-eGFP model for rapid preclinical
      assessment and sensitive monitoring of novel and potential therapeutics. Whole
      body GFP imaging is practical, convenient, inexpensive, and rapid, and these
      advantages should enable a high throughput when evaluating in vivo efficacy of
      new potential antimyeloma therapeutics and assessing response to treatment.

PMID- 17541033
TI  - A novel treatment strategy targeting Aurora kinases in acute myelogenous
      leukemia.
AB  - The Aurora kinases play an important role in chromosome alignment, segregation,
      and cytokinesis during mitosis. Aberrant expression of these kinases occurs in
      solid tumors and is associated with aneuploidy and carcinogenesis. We found in
      this study that Aurora kinase A and B were aberrantly expressed in a variety of
      types of human leukemia cell lines (n = 15, e.g., PALL-1, PALL-2, HL-60, NB4, MV4
      11, etc.), as well as freshly isolated leukemia cells from individuals with acute
      myelogenous leukemia (n = 44) compared with bone marrow mononuclear cells from
      healthy volunteers (n = 11), as measured by real-time PCR. ZM447439 is a novel
      selective Aurora kinase inhibitor. The compound induced growth inhibition, caused
      accumulation of cells with 4N/8N DNA content, and mediated apoptosis of human
      leukemia cells as measured by thymidine uptake, cell cycle analysis, and annexin
      V staining, respectively. Especially profound growth inhibition occurred with the
      PALL-1 and PALL-2 cells, which possess wild-type p53 gene. In contrast, ZM447439
      did not inhibit clonogenic growth of myeloid committed stem cells harvested from
      healthy normal volunteers. Taken together, inhibition of Aurora kinases may be a
      promising treatment strategy for individuals with leukemia.

PMID- 17541034
TI  - Suppression of pancreatic tumor growth by combination chemotherapy with sulindac
      and LC-1 is associated with cyclin D1 inhibition in vivo.
AB  - The design of novel targeted or combination therapies may improve treatment
      options for pancreatic cancer. Two targets of recent interest are nuclear factor
      kappaB (NF-kappaB) and cyclooxygenase (COX), known to be activated or
      overexpressed, respectively, in pancreatic cancer. We have previously shown that
      parthenolide, a proapoptotic drug associated with NF-kappaB inhibition, enhanced
      the growth suppression of pancreatic cancer cells by the COX inhibitor sulindac
      in vitro. In the present study, a bioavailable analogue of parthenolide, LC-1,
      and sulindac were evaluated in vivo using a xenograft model of human pancreatic
      cancer. Treatment groups included placebo, low-dose/high-dose LC-1 (20 and 40
      mg/kg), low-dose/high-dose sulindac (20 and 60 mg/kg), and low-dose combination
      LC-1/sulindac (20 mg/kg each). In MiaPaCa-2 xenografts, tumor growth was
      inhibited by either high-dose sulindac or LC-1. In BxPC-3 xenografts, tumor size
      was significantly reduced by treatment with the low-dose LC-1/sulindac
      combination or high-dose sulindac alone (P < 0.05). Immunohistochemistry of BxPC
      3 tumors revealed a significant decrease in Ki-67 and CD31 staining by high-dose
      sulindac, with no significant changes in COX-1/COX-2 levels or activity in any of
      the treatment groups. NF-kappaB DNA-binding activity was significantly decreased
      by high-dose LC-1. Cyclin D1 protein levels were reduced by the low-dose LC
      1/sulindac combination or high-dose sulindac alone, correlating with BxPC-3 tumor
      suppression. These results suggest that LC-1 and sulindac may mediate their
      antitumor effects, in part, by altering cyclin D1 levels. Furthermore, this study
      provides preclinical evidence for the therapeutic efficacy of these agents.

PMID- 17541035
TI  - The peroxisome proliferator-activated receptor-gamma agonist troglitazone
      inhibits transforming growth factor-beta-mediated glioma cell migration and brain
      invasion.
AB  - Gliomas are the most common primary tumors of the central nervous system, with
      glioblastomas as the most malignant entity. Rapid proliferation and diffuse brain
      invasion of these tumors are likely to determine the unfavorable prognosis.
      Considering its promigratory properties, the transforming growth factor-beta (TGF
      beta) signaling pathway has become a major therapeutic target. Analyses of
      resected glioma tissues revealed an intriguing correlation between tumor grade
      and the expression of TGF-beta(1-3) as well as their receptors I and II. Here, we
      analyzed the effects of peroxisome proliferator-activated receptor gamma (PPAR
      gamma) agonists on glioma proliferation, migration, and brain invasion. Using an
      organotypic glioma invasion model, we show that micromolar doses of the PPAR
      gamma activator troglitazone blocked glioma progression without neurotoxic damage
      to the organotypic neuronal environment observed. This intriguing antiglioma
      property of troglitazone seems to be only partially based on its moderate
      cytostatic effects. We identified troglitazone as a potent inhibitor of glioma
      cell migration and brain invasion, which occurred in a PPAR-gamma-independent
      manner. The antimigratory property of troglitazone was in concordance with the
      transcriptional repression of TGF-beta(1-3) and their receptors I and II and
      associated with reduced TGF-beta release. Due to its capacity to counteract TGF
      beta release and glioma cell motility and invasiveness already at low micromolar
      doses, troglitazone represents a promising drug for adjuvant therapy of glioma
      and other highly migratory tumor entities.

PMID- 17541036
TI  - Suppression of lung cancer tumor growth in a nude mouse model by the Ras
      inhibitor salirasib (farnesylthiosalicylic acid).
AB  - Aberrant Ras pathway functions contribute to the malignant phenotype of lung
      cancers. Inhibitors of Ras might therefore be considered as potential drugs for
      lung cancer therapy. Here, we show that the Ras inhibitor farnesylthiosalicylic
      acid (salirasib) inhibits proliferation of human lung cancer cells harboring a
      mutated K-ras gene (A549, H23, or HTB54) or overexpressing a growth factor
      receptor (H1299 or HTB58) and enhances the cytotoxic effect of the
      chemotherapeutic drug gemcitabine. Salirasib inhibited active K-Ras in A549
      cells, reversed their transformed morphology, and inhibited their anchorage
      independent growth in vitro. Tumor growth in A549 and HTB58 cell nude mouse
      models was inhibited by i.p. administration of salirasib. P.o. formulated
      salirasib also inhibited A549 cell tumor growth. Our results suggest that p.o.
      salirasib may be considered as a potential treatment for lung cancer therapy.

PMID- 17541037
TI  - The FDA pediatric advisories and changes in diagnosis and treatment of pediatric
      depression.

PMID- 17541038
TI  - Depression in the older adult: the challenge of medical comorbidity.

PMID- 17541039
TI  - Gene-environment interactions with cognition in late life and compression of
      morbidity.

PMID- 17541040
TI  - Do all roads lead to Rome? New findings on borderline personality disorder.

PMID- 17541041
TI  - Why does the worldwide prevalence of childhood attention deficit hyperactivity
      disorder matter?

PMID- 17541042
TI  - Issues for DSM-V: clinical staging: a heuristic pathway to valid nosology and
      safer, more effective treatment in psychiatry.

PMID- 17541043
TI  - The homocysteine hypothesis of depression.
AB  - High levels of homocysteine are associated with cerebrovascular disease,
      monoamine neurotransmitters, and depression of mood. A plausible hypothesis for
      these associations is that high homocysteine levels cause cerebral vascular
      disease and neurotransmitter deficiency, which cause depression of mood. The
      homocysteine depression hypothesis, if true, would mandate inclusions of imaging
      studies for cerebrovascular disease and measures of homocysteine, folate, and B12
      and B6 vitamins in the clinical evaluation of older depressed patients.
      Longitudinal studies and clinical trials should be designed to challenge the
      hypothesis.

PMID- 17541044
TI  - Neuroleptic malignant syndrome.

PMID- 17541045
TI  - Treatment of psychiatric symptoms associated with a frontal lobe tumor through
      surgical resection.

PMID- 17541046
TI  - From asylum to hospital to psychiatric health care system.

PMID- 17541047
TI  - Decline in treatment of pediatric depression after FDA advisory on risk of
      suicidality with SSRIs.
AB  - OBJECTIVE: In October 2003, the U.S. Food and Drug Administration (FDA) issued a
      public health advisory about the risk of suicidality in pediatric patients taking
      selective serotonin reuptake inhibitors (SSRIs) for depression. This study used
      data from a large national pediatric cohort to examine patterns of diagnosis of
      depression, prescription of antidepressants, prescription of pharmacological
      alternatives to antidepressants, and use of psychosocial care before and after
      the FDA advisory was issued. METHOD: A large pediatric cohort with newly
      diagnosed episodes of depression was created from a national integrated claims
      database of managed care plans from October 1998 to September 2005 (N=65,349).
      Time-series models were used to compare diagnosing and prescribing trends during
      the 2 years after the FDA advisory and the expected trends based on data from the
      5-year period preceding the advisory. RESULTS: From 1999 to 2004, pediatric
      diagnoses of depression increased from 3 to 5 per 1,000. After the FDA advisory
      was issued, the national rate decreased to 1999 levels, a significant deviation
      from the historical trend. Pediatricians and nonpediatrician primary care
      physicians accounted for the largest reductions in new diagnoses. Among patients
      with depression, the proportion receiving no antidepressant increased to three
      times the rate predicted by the preadvisory trend, and SSRI prescription fills
      were 58% lower than predicted by the trend. There was no evidence of a
      significant increase in use of treatment alternatives (psychotherapy, atypical
      antipsychotics, and anxiolytics). CONCLUSIONS: The FDA advisory was associated
      with significant reductions in aggregate rates of diagnosis and treatment of
      pediatric depression.

PMID- 17541048
TI  - Recovery from major depression in older adults receiving augmentation of
      antidepressant pharmacotherapy.
AB  - OBJECTIVE: Few data are available concerning the utility of augmentation in late
      life depression treatment. The authors examined likelihood, speed, and predictors
      of recovery in older adults receiving augmentation pharmacotherapy after
      inadequate response to standardized treatment with paroxetine plus interpersonal
      psychotherapy. METHOD: Depression levels were monitored during open treatment in
      195 adults age 70 or older. Patients were grouped by whether they required
      augmentation (bupropion, nortriptyline, or lithium) and compared on likelihood,
      time, and predictors of recovery. RESULTS: Augmentation was required for 105
      patients (53.8%) because of inadequate treatment response (N=77) or response
      followed by relapse (N=28). Of these patients, 69 received augmentation and 36
      did not (primarily because of consent withdrawal or comorbid medical conditions).
      Patients receiving augmentation showed lower recovery rates than patients never
      requiring augmentation: recovery occurred in 50.0% of patients receiving it
      because of inadequate response, 66.7% of those receiving it after early relapse,
      and 86.7% of patients never requiring augmentation. Patients receiving
      augmentation because of inadequate response recovered more slowly, with modestly
      more side effects than other patients. Greater medical burden and anxiety
      predicted slower recovery. CONCLUSIONS: Despite a lower likelihood of recovery in
      elderly people receiving augmentation, the recovery by over one-half of such
      patients suggests the value of augmentation for those able to tolerate it. Need
      for augmentation presages slower recovery in patients showing initial inadequate
      response; those requiring it after early relapse recovered more quickly.
      Strategies to further improve the likelihood and speed of recovery after initial
      treatment failure are needed.

PMID- 17541049
TI  - Efficacy of duloxetine on cognition, depression, and pain in elderly patients
      with major depressive disorder: an 8-week, double-blind, placebo-controlled
      trial.
AB  - OBJECTIVE: This study compared the effects of duloxetine, 60 mg/day, versus
      placebo on cognition, depression, and pain in elderly patients with recurrent
      major depressive disorder. METHOD: Patients were randomly assigned (2:1) to
      duloxetine, 60 mg/day (N=207), or placebo (N=104) for 8 weeks in a double-blind
      study. The primary outcome measure was a prespecified composite cognitive score
      composed of four individual tests. Secondary measures included the Geriatric
      Depression Scale, the Hamilton Depression Rating Scale, the Visual Analogue Scale
      assessing pain, and standard safety and tolerability assessments. RESULTS:
      Patients had a median age of 72 years (range=65-90). Duloxetine demonstrated
      significantly greater improvement in the composite cognitive score versus placebo
      (least-squares mean change from baseline to endpoint: 1.95 versus 0.76), driven
      by improved verbal learning and memory. Duloxetine treatment showed significantly
      greater baseline-to-endpoint reductions in both Hamilton depression scale (-6.49
      versus -3.72) and Geriatric Depression Scale (-4.07 versus -1.34) total scores
      compared with placebo. Hamilton depression scale response (37.3% versus 18.6%)
      and remission (27.4% versus 14.7%) rates at endpoint were significantly higher
      for duloxetine than for placebo. Duloxetine significantly improved Visual
      Analogue Scale scores for back pain and time in pain while awake versus placebo.
      Significantly fewer patients receiving duloxetine withdrew from the study because
      of lack of efficacy (2.9% versus 9.6%); the incidences of discontinuation due to
      adverse events were similar for duloxetine and placebo (9.7% versus 8.7%).
      CONCLUSIONS: Duloxetine improved cognition, depression, and some pain measures
      and was safe and well tolerated in elderly patients with recurrent major
      depressive disorder.

PMID- 17541050
TI  - Nursing home placement, day care use, and cognitive decline in Alzheimer's
      disease.
AB  - OBJECTIVE: People with Alzheimer's disease are often placed in a nursing home,
      sometimes after using adult day care services. How affected persons function
      during this potentially difficult transition is not well understood. The aim of
      this study was to examine the associations of day care use and nursing home
      placement with the rate of cognitive decline in Alzheimer's disease. METHOD: The
      participants were 432 older persons with Alzheimer's disease who were recruited
      from health care settings in the Chicago area. At baseline, they lived in the
      community and were using day care services a mean 1.7 days per week. At 6-month
      intervals for up to 4 years, they completed nine cognitive tests from which a
      composite measure of global cognition was derived. RESULTS: On average, cognition
      declined at a gradually increasing rate during the study period. Nursing home
      placement was associated with a decrease in the level of cognition and an
      acceleration in the rate of cognitive decline. Day care use at baseline was not
      related to cognitive decline in initial analyses, but it interacted with nursing
      home placement such that higher level of day care use substantially reduced
      association of placement with accelerated cognitive decline. Education interacted
      with placement such that more schooling was associated with a greater increase in
      cognitive decline upon nursing home placement, but prior day care use also
      attenuated this association. CONCLUSIONS: Nursing home placement is associated
      with accelerated short-term cognitive decline in Alzheimer's disease. Prior
      experience in adult day care may lessen this association.

PMID- 17541051
TI  - Correlations between apolipoprotein E epsilon4 gene dose and whole brain atrophy
      rates.
AB  - OBJECTIVE: The purpose of this study was to characterize the relationship between
      whole brain atrophy rates and three levels of genetic risk for Alzheimer's
      disease in cognitively normal persons. The authors previously found accelerated
      whole brain atrophy rates in patients with probable Alzheimer's disease by
      computing changes in brain volume from sequential magnetic resonance images
      (MRIs). METHODS: The authors assessed 36 late-middle-aged persons from three
      genetic groups: those with two, one, and no copies of the apolipoprotein E (APOE)
      epsilon4 allele, a common Alzheimer's disease susceptibility gene. The
      participants had clinical ratings, neuropsychological tests, and volumetric T1
      weighted MRIs during a baseline visit and again approximately 2 years later. Two
      different image-analysis techniques, brain boundary shift integration and
      iterative principal component analysis, were used to compute whole brain atrophy
      rates. RESULTS: While there were no baseline, follow-up, or between-visit
      differences in the clinical ratings or neuropsychological test scores among the
      three subject groups, whole brain atrophy rates were significantly greater in the
      epsilon4 homozygote group than in noncarriers and were significantly correlated
      with epsilon4 gene dose (i.e., the number of epsilon4 alleles in a person's APOE
      genotype). CONCLUSION: Since APOE epsilon4 gene dose is associated with an
      increased risk of Alzheimer's disease and a younger median age at dementia onset,
      this study suggests an association between the risk of Alzheimer's disease and
      accelerated brain atrophy rates before the onset of cognitive impairment.

PMID- 17541052
TI  - Evaluating three treatments for borderline personality disorder: a multiwave
      study.
AB  - OBJECTIVE: The authors examined three yearlong outpatient treatments for
      borderline personality disorder: dialectical behavior therapy, transference
      focused psychotherapy, and a dynamic supportive treatment. METHOD: Ninety
      patients who were diagnosed with borderline personality disorder were randomly
      assigned to transference-focused psychotherapy, dialectical behavior therapy, or
      supportive treatment and received medication when indicated. Prior to treatment
      and at 4-month intervals during a 1-year period, blind raters assessed the
      domains of suicidal behavior, aggression, impulsivity, anxiety, depression, and
      social adjustment in a multiwave study design. RESULTS: Individual growth curve
      analysis revealed that patients in all three treatment groups showed significant
      positive change in depression, anxiety, global functioning, and social adjustment
      across 1 year of treatment. Both transference-focused psychotherapy and
      dialectical behavior therapy were significantly associated with improvement in
      suicidality. Only transference-focused psychotherapy and supportive treatment
      were associated with improvement in anger. Transference-focused psychotherapy and
      supportive treatment were each associated with improvement in facets of
      impulsivity. Only transference-focused psychotherapy was significantly predictive
      of change in irritability and verbal and direct assault. CONCLUSIONS: Patients
      with borderline personality disorder respond to structured treatments in an
      outpatient setting with change in multiple domains of outcome. A structured
      dynamic treatment, transference-focused psychotherapy was associated with change
      in multiple constructs across six domains; dialectical behavior therapy and
      supportive treatment were associated with fewer changes. Future research is
      needed to examine the specific mechanisms of change in these treatments beyond
      common structures.

PMID- 17541053
TI  - The subsyndromal phenomenology of borderline personality disorder: a 10-year
      follow-up study.
AB  - OBJECTIVE: The purpose of this study was to characterize the course of 24
      symptoms of borderline personality disorder in terms of time to remission.
      METHOD: The borderline psychopathology of 362 patients with personality
      disorders, all recruited during inpatient stays, was assessed using two
      semistructured interviews of proven reliability. Of these, 290 patients met DSM
      III-R criteria as well as Revised Diagnostic Interview for Borderlines criteria
      for borderline personality disorder, and 72 met DSM-III-R criteria for another
      axis II disorder. Over 85% of the patients were reinterviewed at five distinct 2
      year follow-up waves by interviewers blind to all previously collected
      information. RESULTS: Among borderline patients, 12 of the 24 symptoms studied
      showed patterns of sharp decline over time and were reported at 10-year follow-up
      by less than 15% of the patients who reported them at baseline. The other 12
      symptoms showed patterns of substantial but less dramatic decline over the follow
      up period. Symptoms reflecting core areas of impulsivity (e.g., self-mutilation
      and suicide efforts) and active attempts to manage interpersonal difficulties
      (e.g., problems with demandingness/entitlement and serious treatment regressions)
      seemed to resolve the most quickly. In contrast, affective symptoms reflecting
      areas of chronic dysphoria (e.g., anger and loneliness/emptiness) and
      interpersonal symptoms reflecting abandonment and dependency issues (e.g.,
      intolerance of aloneness and counterdependency problems) seemed to be the most
      stable. CONCLUSIONS: The results suggest that borderline personality disorder may
      consist of both symptoms that are manifestations of acute illness and symptoms
      that represent more enduring aspects of the disorder.

PMID- 17541054
TI  - Therapist affect focus and patient outcomes in psychodynamic psychotherapy: a
      meta-analysis.
AB  - OBJECTIVE: The authors systematically examined the relationship between therapist
      facilitation of patient emotional experience/expression and outcome in
      psychodynamic psychotherapy. METHOD: Computer and manual searches were conducted
      for relevant publications, and 10 independent samples of short-term dynamic
      psychotherapy were included in a meta-analysis. Data analysis included
      calculation of an overall effect size of the relationship between therapist
      affect focus and outcome, statistical significance, and test for homogeneity. In
      addition, moderator analyses were conducted to examine the potential impact of
      type of outcome construct used and the methodological quality of individual
      studies. RESULTS: The overall average weighted effect size across all outcome
      types was statistically significant (r=0.30), and the homogeneity statistic was
      nonsignificant. Moderator analyses indicated a statistically significant
      relationship between therapist facilitation of patient emotional
      experience/expression and outcome when more than one outcome construct was
      included but not when either a single or an unclear outcome construct was used.
      There were no significant relationships between methodological quality and the
      size of the effects, although use of audio- or videotaping for supervision
      demonstrated a moderate effect. CONCLUSIONS: These data indicate that therapist
      facilitation of patient affective experience/expression is associated with
      patient improvement over the course of psychodynamic psychotherapy. Although the
      size of this relationship was not significantly related to methodological
      quality, results suggest the importance of close supervision of actual techniques
      through the use of audio- or videotapes. Additionally, results highlight the
      importance of defining outcome in a multidimensional way to properly assess
      theoretically relevant effects.

PMID- 17541055
TI  - The worldwide prevalence of ADHD: a systematic review and metaregression
      analysis.
AB  - OBJECTIVE: The worldwide prevalence estimates of attention deficit hyperactivity
      disorder (ADHD)/hyperkinetic disorder (HD) are highly heterogeneous. Presently,
      the reasons for this discrepancy remain poorly understood. The purpose of this
      study was to determine the possible causes of the varied worldwide estimates of
      the disorder and to compute its worldwide-pooled prevalence. METHOD: The authors
      searched MEDLINE and PsycINFO databases from January 1978 to December 2005 and
      reviewed textbooks and reference lists of the studies selected. Authors of
      relevant articles from North America, South America, Europe, Africa, Asia,
      Oceania, and the Middle East and ADHD/HD experts were contacted. Surveys were
      included if they reported point prevalence of ADHD/HD for subjects 18 years of
      age or younger from the general population or schools according to DSM or ICD
      criteria. RESULTS: The literature search generated 9,105 records, and 303 full
      text articles were reviewed. One hundred and two studies comprising 171,756
      subjects from all world regions were included. The ADHD/HD worldwide-pooled
      prevalence was 5.29%. This estimate was associated with significant variability.
      In the multivariate metaregression model, diagnostic criteria, source of
      information, requirement of impairment for diagnosis, and geographic origin of
      the studies were significantly associated with ADHD/HD prevalence rates.
      Geographic location was associated with significant variability only between
      estimates from North America and both Africa and the Middle East. No significant
      differences were found between Europe and North America. CONCLUSIONS: Our
      findings suggest that geographic location plays a limited role in the reasons for
      the large variability of ADHD/HD prevalence estimates worldwide. Instead, this
      variability seems to be explained primarily by the methodological characteristics
      of studies.

PMID- 17541056
TI  - Childhood sibling relationships as a predictor of major depression in adulthood:
      a 30-year prospective study.
AB  - OBJECTIVE: The authors examined the quality of sibling relationships in childhood
      as a predictor of major depression in adulthood. METHOD: Study subjects were 229
      men selected for mental and physical health and followed from ages 20 through 50
      and beyond as part of a study of adult psychosocial development. Data were
      obtained from interviews with participants and their parents at intake and from
      follow-up interviews and self-report questionnaires completed by participants at
      regular intervals. These data were used to rate the quality of relationships with
      siblings, the quality of parenting received in childhood, and family history of
      depression as well as the occurrence, by age 50, of major depression, alcoholism,
      and use of mood-altering drugs (tranquilizers, sleeping pills, and stimulants).
      RESULTS: Poorer relationships with siblings prior to age 20 and a family history
      of depression independently predicted both the occurrence of major depression and
      the frequency of use of mood-altering drugs by age 50, even after adjustment for
      the quality of childhood relationships with parents. Poor relationships with
      parents in childhood did not predict the occurrence of depression by age 50 when
      family history of depression and the quality of relationships with siblings were
      taken into account. Quality of sibling relationships and family history of
      depression did not predict later alcohol abuse or dependence. CONCLUSIONS: Poor
      sibling relationships in childhood may be an important and specific predictor of
      major depression in adulthood. Further study of links between childhood sibling
      relationships and adult depression is warranted.

PMID- 17541057
TI  - A developmental fMRI study of self-regulatory control in Tourette's syndrome.
AB  - OBJECTIVE: Disturbances in the maturation of neural systems that mediate self
      regulatory processes may contribute to the development of Tourette's syndrome by
      releasing motor and vocal tics from regulatory control. The purpose of this study
      was to examine the age correlates of functional activity in neural circuits that
      subserve self-regulatory control in children and adults with Tourette's syndrome.
      METHOD: The participants were 136 children and adults, which included 66
      Tourette's syndrome patients and 70 healthy comparison subjects. During
      performance of the Stroop interference task, the authors compared the functional
      magnetic resonance imaging (fMRI) blood-oxygen-level dependent response in
      patients with Tourette's syndrome with that of healthy comparison subjects.
      General linear modeling of Stroop-related activations was used to compare the
      differential effects of age and behavioral performance on changes in self
      regulatory control between the two diagnostic groups. RESULTS: Although the
      correlations of age with behavioral performance on the Stroop task were similar
      between patients with Tourette's syndrome and healthy comparison subjects, the
      two groups differed significantly in their correlations of age with the magnitude
      of regional brain activation during the task. Interactions of age with diagnosis
      were detected in the ventral prefrontal (Brodmann's areas 10 and 24) and
      posterior cingulate cortices (Brodmann's area 31), and post hoc analyses
      indicated that subjects with Tourette's syndrome deactivated these regions less
      with advancing age. Greater activation of bilateral frontostriatal regions
      (Brodmann's areas 9/46, 45/46; lenticular nucleus; and thalamus) accompanied
      poorer performance in the patient group, which-in the presence of normal
      behavioral performance on the Stroop task-suggests that greater activation of the
      frontostriatal systems helps to maintain task performance in individuals with
      Tourette's syndrome. CONCLUSIONS: Normative developmental correlates of activity
      in frontostriatal circuits that subserve self-regulatory control are disturbed in
      persons with Tourette's syndrome. These aberrant developmental correlates are
      likely a consequence of greater anatomical and functional disturbances in these
      circuits in adults with Tourette's syndrome, which leads to impaired regulation
      of tic behaviors. Reduced default-mode processing in ventral prefrontal and
      posterior cingulate cortices in adults with Tourette's syndrome suggests the
      presence of greater difficulty in engaging mental processes that become active
      when freed from the demands of more challenging cognitive tasks. However,
      individuals with Tourette's syndrome appear to co-opt normal developmental
      processes in circuits that subserve age-related improvement in self-regulatory
      control while presumably struggling to maintain adequate task performance.

PMID- 17541058
TI  - Preventive effect of beta-adrenoceptor blockade on glucocorticoid-induced memory
      retrieval deficits.
AB  - OBJECTIVE: Elevated glucocorticoid levels impair retrieval of emotional
      information, and animal studies indicate that this effect depends on concurrent
      emotional arousal-induced increases in noradrenergic transmission within the
      brain. The authors investigated whether the beta-adrenoceptor antagonist
      propranolol blocks glucocorticoid-induced memory retrieval impairments in human
      subjects. METHOD: In a double-blind, placebo-controlled study, 42 healthy
      volunteers were presented a set of words with variable emotionality and asked to
      learn them for recall. A day later, cortisone (25 mg), propranolol (40 mg), or
      both drugs were administered orally 1 hour before a free-recall test. RESULTS:
      Cortisone selectively impaired the recall of emotionally arousing words by 42%.
      This impairment was blocked by the concurrent administration of propranolol.
      Propranolol alone did not affect recall of either emotional or neutral words.
      CONCLUSIONS: A pharmacological blockade of beta-adrenoceptors prevents
      glucocorticoid-induced memory retrieval deficits in human subjects. This finding
      may have important implications for the treatment of memory deficits in
      hypercortisolemic states, such as stress and depression.

PMID- 17541060
TI  - Symptoms of ADHD or marijuana use?

PMID- 17541059
TI  - Does percent body fat predict outcome in anorexia nervosa?
AB  - OBJECTIVE: The goal of this study was to investigate the relationship of body
      composition and neuroendocrine levels with clinical outcome in women with
      anorexia nervosa in a relapse-prevention trial. METHOD: Body composition and
      fasting cortisol and leptin levels were assessed before random assignment in 32
      weight-recovered subjects with anorexia nervosa from the New York site of the
      Fluoxetine to Prevent Relapse in Women With Anorexia Nervosa trial. Clinical
      outcome at the end of study participation was defined using modified Morgan
      Russell criteria (full, good, fair, poor), then dichotomized into treatment
      "success" or "failure." RESULTS: In a binary logistic regression model examining
      the effect of percent body fat, body mass index, anorexia nervosa subtype, waist
      to-hip ratio, and serum cortisol and leptin levels on treatment outcome, only
      percent body fat was significantly associated with outcome. CONCLUSIONS: In
      recently weight-restored women with anorexia nervosa, lower percent body fat was
      associated with poor long-term outcome.

PMID- 17541061
TI  - Do nonspecific factors influence psychotherapy outcome?

PMID- 17541062
TI  - Can traumatized children report revenge fantasies?

PMID- 17541063
TI  - Evolving treatments for panic disorder.

PMID- 17541064
TI  - BKca channel in autism and mental retardation.

PMID- 17541065
TI  - Abacavir sulfate and mania in HIV.

PMID- 17541066
TI  - Buprenorphine for postoperative pain following general surgery in a buprenorphine
      maintained patient.

PMID- 17541067
TI  - Membrane-type 1 matrix metalloproteinase stimulates cell migration through
      epidermal growth factor receptor transactivation.
AB  - Proteolysis of extracellular matrix proteins by membrane-type 1 matrix
      metalloproteinase (MT1-MMP) plays a pivotal role in tumor and endothelial cell
      migration. In addition to its proteolytic activity, several studies indicate that
      the proinvasive properties of MT1-MMP also involve its short cytoplasmic domain,
      but the specific mechanisms mediating this function have yet to be fully
      elucidated. Having previously shown that the serum factor sphingosine 1-phosphate
      stimulates MT1-MMP promigratory function through a process that involves its
      cytoplasmic domain, we now extend these findings to show that this cooperative
      interaction is permissive to cellular migration through MT1-MMP-dependent
      transactivation of the epidermal growth factor receptor (EGFR). In the presence
      of sphingosine 1-phosphate, MT1-MMP stimulates EGFR transactivation through a
      process that is dependent upon the cytoplasmic domain of the enzyme but not its
      catalytic activity. The MT1-MMP-induced EGFR transactivation also involves G(i)
      protein signaling and Src activities and leads to enhanced cellular migration
      through downstream extracellular signal-regulated kinase activation. The present
      study, thus, elucidates a novel role of MT1-MMP in signaling events mediating
      EGFR transactivation and provides the first evidence of a crucial role of this
      receptor activity in MT1-MMP promigratory function. Taken together, our results
      suggest that the inhibition of EGFR may represent a novel target to inhibit MT1
      MMP-dependent processes associated with tumor cell invasion and angiogenesis.

PMID- 17541068
TI  - Enhancing ventilatory strategies for the critically ill--proportional assist
      ventilation.

PMID- 17541069
TI  - Strategies to attenuate the catabolic response to surgery and improve
      perioperative outcomes.

PMID- 17541070
TI  - Tracheal pressure regulated volume assist ventilation in acute respiratory
      failure.
AB  - PURPOSE: Proportional assist ventilation (PAV) uses volume assist (VAV) and flow
      assist ventilation (FAV) to reduce elastic and resistive effort, respectively.
      Proportional assist ventilation may be difficult to apply clinically,
      particularly due to FAV related considerations. It was hypothesized that
      regulating tracheal (Ptr) rather than airway opening pressure (Pao), to overcome
      endotracheal tube related resistive effort, during VAV would provide an effective
      alternative method of ventilation. We therefore compared the effects of Pao and
      Ptr regulated VAV on breathing pattern and inspiratory effort. METHODS: In seven
      intubated patients, flow, volume, Pao, Ptr, esophageal and transdiaphragmatic
      pressure were measured during VAV (0-80% respiratory system elastance) using Pao
      vs Ptr to regulate ventilator applied pressure. Breathing pattern and the
      pressure-time integral of the inspiratory muscles (integralP(mus) . dt) and
      diaphragm (integralP(di) . dt) were determined. RESULTS: Compared to spontaneous
      breathing, the respiratory rate to tidal volume ratio, or rapid shallow breathing
      index (RSBI), improved progressively with increasing VAV (130 +/- 64 vs 70 +/-
      35, VAV 0 vs 80%; P < 0.05) while inspiratory effort fell (integralP(mus) . dt =
      39.6 +/- 7.5 vs 28.5 +/- 7.2 cm H(2)O.sec.L(-1), integralP(di) . dt, = 35.4 +/-
      7.8 vs 24.2 +/- 5.9 cm H(2)O.sec.L(-1), VAV 0 vs 80%; P < 0.05) due to a decrease
      in elastic related effort. At any given level of support, there was further
      reduction in RSBI, integralP(mus) . dt, and integralP(di) . dt (which averaged
      23.6 +/- 2.7, 33.7 +/- 4.4, and 38.5 +/- 5.1%, respectively; P < 0.05) for Ptr
      compared to Pao regulated VAV due to a decrease in resistive effort. CONCLUSIONS:
      Tracheal pressure regulated VAV can be a simple and effective method of partial
      ventilatory support in acute respiratory failure. Further work will be needed to
      determine its efficacy and potential benefit relative to PAV and other modes of
      ventilation in routine clinical practice.

PMID- 17541071
TI  - Bymixer system can measure O2 uptake and CO2 elimination in the anesthesia circle
      circuit.
AB  - BACKGROUND: The ability to measure carbon dioxide elimination (Vco(2)), oxygen
      uptake (Vo(2)), and R (respiratory exchange ratio, Vco(2)/Vo(2)) during
      anesthesia may help the non-invasive detection of critical events (e.g., abrupt
      decrease in cardiac output) and metabolic upset (e.g., onset of anaerobic
      metabolism). METHODS: We have developed a new clinical bymixer (inline mixing
      chamber) that can measure mixed inspired and expired gas fractions in the
      anesthesia circle circuit. The addition of a standard anesthesia gas analyzer and
      flowmeter, and a new airway temperature and humidity sensor, allow determinations
      of Vco(2) and Vo(2) at the airway opening of the circle circuit. Over a range of
      tidal volume and frequency, Vco(2) and Vo(2) were compared to reference values
      generated by the combustion of metered liquid ethanol in a new metabolic lung
      simulator. RESULTS: By linear regression, bymixer-flow measurements of Vco(2)
      (slope = 1.02, Y-intercept = -5.31, coefficient of determination, R(2) = 0.998)
      and Vo(2) (slope = 1.05, Y-intercept = -4.34, R(2) = 0.993) correlated closely to
      the reference values generated by the metabolic lung simulator. Limits of
      agreement analysis generated percent errors (mean +/- 1.96 SD) of -1.2 +/- 7.2%
      for Vco(2) and 2.5 +/- 9.8% for Vo(2). CONCLUSIONS: The new clinical bymixer is
      compact, lightweight, disposable, inexpensive, and has a fast and adjustable
      response time (time constant about 14 sec). Anesthesia circle circuit integrity
      is maintained. Bymixer-flow measurements of Vco(2) and Vo(2) are accurate and may
      add to clinical monitoring under anesthesia and surgery.

PMID- 17541072
TI  - Cervical spine motion: a fluoroscopic comparison of Shikani Optical Stylet vs
      Macintosh laryngoscope.
AB  - PURPOSE: The optimal technique to manage the airway in patients presenting with a
      potential or documented cervical spine (C-spine) injury remains unresolved. Using
      fluoroscopic video assessment, C-spine motion during laryngoscopy with a Shikani
      Optical Stylet (SOS) was compared to C-spine motion during intubation using a
      Macintosh blade. METHODS: Twenty-four healthy surgical patients gave written
      consent to participate in a crossover randomized controlled trial; all patients
      were subjected to both Macintosh and Shikani laryngoscopy with manual inline
      stabilization following induction of anesthesia. The C-spine motion was examined
      at four areas: the occiput-C1 junction, C1-C2 junction, C2-C5 motion segment, and
      C5-thoracic motion segment. The time required for laryngoscopy was also measured
      (duration > 120 sec was deemed a failure of the laryngoscopy technique). RESULTS:
      On average, C-spine motion was 52% less (P < 0.02) at three of the motion
      segments studied, occiput-C1, C2-C5, and C5-thoracic when comparing SOS vs
      Macintosh laryngoscopy. There was no difference between techniques at the C1-C2
      segment. Laryngoscopy with SOS (28 +/- 17 sec) took longer than with Macintosh
      blade (17 +/- 7 sec), P < 0.01. There were two failures out of 23 using the SOS,
      vs none with the Macintosh blade. CONCLUSION: For patients in whom C-spine
      movement is undesirable, use of the SOS may limit neck movement, while modestly
      increasing the time required to intubate, and/or the risk of procedure failure.

PMID- 17541073
TI  - Efficacy of preoxygenation using tidal volume and deep breathing techniques with
      and without prior maximal exhalation.
AB  - PURPOSE: We evaluated the influence of prior maximal exhalation on preoxygenation
      in 15 adult volunteers using tidal volume breathing (TVB) for five minutes and
      deep breathing (DB) for two minutes with and without prior maximal exhalation.
      METHODS: Inspired and end-tidal oxygen, nitrogen and carbon dioxide were
      monitored continuously and recorded during room air breathing and at 30-sec
      intervals during 100% oxygen TVB or DB (rate of 8 breaths.min(-1)). RESULTS:
      Tidal volume breathing with prior maximal exhalation resulted in an end-tidal
      oxygen concentration (ETO(2)) slightly higher (P = 0.028) at 0.5 and 1.0 min as
      compared with TVB without prior maximal exhalation at the same time periods.
      Regardless of whether TVB was preceded by maximal exhalation or not, 2.5 min was
      required to reach a mean ETO(2) value of 90% or higher. With DB, there were no
      differences in ETO(2) values at any time period and 1.5 min was required to reach
      an ETO(2) of 90% or greater, with or without prior maximal exhalation.
      CONCLUSIONS: Maximal exhalation prior to TVB slightly steepens the initial rise
      in ETO(2) during the first minute, but confers no real benefit if maximal
      preoxygenation is the goal. Maximal exhalation prior to DB has no added value in
      enhancing preoxygenation.

PMID- 17541074
TI  - Inhibitory effect of tramadol on vasorelaxation mediated by ATP-sensitive K+
      channels in rat aorta.
AB  - PURPOSE: Tramadol produces a conduction block similar to lidocaine by exerting a
      local anesthetic-like effect. The aims of this in vitro study were to determine
      the effects of tramadol on the vasorelaxant response induced by the adenosine
      triphosphate-sensitive K(+) (K(ATP)) channel opener, levcromakalim, in an
      endothelium-denuded rat aorta, and to determine whether this effect of tramadol
      is stereoselective. METHODS: The effects of tramadol (racemic, R(-) and S(+): 10(
      6), 10(-5), 5 x 10(-5) M), and glibenclamide on the levcromakalim dose-response
      curve were assessed in aortic rings that had been pre-contracted with
      phenylephrine. In the rings pretreated independently with naloxone, and
      glibenclamide, the levcromakalim dose-response curves were generated in the
      presence or absence of tramadol. The effect of tramadol on the dose-response
      curve of diltiazem was assessed. RESULTS: Racemic, R(-) and S(+) tramadol (10(
      5), 5 x 10(-5) M) attenuated (P < 0.0001) levcromakalim-induced relaxation in the
      ring with or without naloxone in a dose-dependent manner. The magnitude of the R(
      )-tramadol-induced attenuation of vasorelaxant response induced by levcromakalim
      was greater (P < 0.05) than that induced by S(+)-tramadol. Glibenclamide almost
      abolished the levcromakalim-induced relaxation. Tramadol, 5 x 10(-5) M, did not
      significantly alter the diltiazem-induced relaxation. CONCLUSION: These results
      suggest that a supraclinical dose (10(-5) M) of tramadol [racemic, R(-) and S(+)]
      attenuates the vasorelaxation mediated by the K(ATP) channels in the rat aorta.
      The R(-) tramadol-induced attenuation of vasorelaxation induced by levcromaklim
      was more potent than that induced by S(+) tramadol. This attenuation is
      independent of opioid receptor activation.

PMID- 17541075
TI  - Case report: management of immediate post-cardiopulmonary bypass massive intra
      cardiac thrombosis.
AB  - PURPOSE: To describe the management of severe acute intracardiac thrombosis in a
      patient who underwent redo multiple valve replacement and valvular repair. The
      diagnostic features, associated risk factors, and anesthetic management are
      reviewed. CLINICAL FEATURES: A 67-yr-old woman undergoing redo mitral and aortic
      mechanical valve replacement and tricuspid annuloplasty under aprotinin
      prophylaxis exhibited severe refractory hypotension that began immediately after
      protamine reversal of intraoperative heparin anticoagulation following separation
      from cardiopulmonary bypass. Intraoperative transesophageal echocardiography
      revealed severe thrombosis in the right atrium, right ventricle and pulmonary
      artery. The patient was managed by immediate reheparinization and return to
      cardiopulmonary bypass (CPB), surgical thrombectomy, and intraoperative
      administration of recombinant tissue-plasminogen activator. After removal of the
      thrombi, and separation from CPB, no further protamine was given. One hundred
      units of blood products and two surgical re-explorations were required to manage
      subsequent massive postoperative bleeding. Acute heparin-induced thrombocytopenia
      (HIT) was ruled out using sensitive assays for HIT antibodies. After 16 days in
      the intensive care unit and 30 more days in hospital, the patient was
      subsequently transferred to a chronic care facility and succumbed several weeks
      later. CONCLUSION: Acute intraoperative thrombosis is a rare and potentially
      fatal complication of cardiac surgery. Intraoperative transesophageal
      echocardiography was essential for rapid diagnosis in this case. Multiple
      interacting prothrombotic factors (e.g., aprotinin use, acquired antithrombin
      deficiency, long pump time, post-protamine status, transfusion of blood
      components) were likely contributing factors related to this rare complication.

PMID- 17541076
TI  - Case report: Successful labour epidural analgesia in a patient with
      spinocerebellar ataxia.
AB  - PURPOSE: To report the favourable outcome associated with epidural analgesia in a
      parturient with spinocerebellar ataxia (SCA). CLINICAL FEATURES: A 34-yr-old
      patient, G2 P0, presented at term with a history of SCA since the age of 22
      characterized by slurred speech, balance and gait disturbances, diplopia and
      nystagmus. A magnetic resonance imaging of the brain at the age of 27 showed
      cerebellar degeneration. Neurological examination revealed an unsteady, wide
      based gait, nystagmus, mild dysarthria, moderate finger to nose ataxia, absent
      reflexes in all upper and lower limbs, sensory loss to vibration and temperature
      discrimination up to the level of both knees, and normal motor strength. The
      patient presented for induction of labour at 40 weeks and requested epidural
      analgesia, which was performed in the usual manner. Following a negative test
      dose of 3 mL of 2% lidocaine, a loading dose of 10 mL of 0.125% bupivacaine was
      administered, and maintenance of analgesia was achieved with a mixture of
      bupivacaine 0.0625% and fentanyl 2 microg.mL(-1). The patient required standard
      doses of the epidural mixture, and experienced effective analgesia for labour and
      delivery. Her recovery was uneventful and no subsequent neurological deficit was
      detected up to two years after delivery. CONCLUSIONS: Neurological disorders may
      contraindicate regional anesthesia, and the decision to proceed with a regional
      technique should be based on the pathophysiology and severity of each particular
      case. Uneventful epidural analgesia was provided to a parturient with SCA, with
      no long term effects detected up to two years after delivery.

PMID- 17541077
TI  - Case report: anesthetic management for sequential Cesarean delivery and
      laminectomy.
AB  - PURPOSE: To describe the anesthetic considerations for a near-term parturient
      with progressive cauda equina syndrome who required Cesarean delivery followed
      immediately by decompression lumbar discectomy and laminectomy in the prone
      position. CLINICAL FEATURES: A 33-yr-old woman presented at 35 weeks gestation
      with severe L5-S1 disc herniation causing motor and sensory neuronal dysfunction
      in the lower limbs accompanied by bowel and bladder dysfunction. After urgent
      multidisciplinary consultations, a decision was made to proceed with general
      anesthesia for Cesarean delivery in the supine position with left uterine
      displacement, followed immediately thereafter by L5-S1 discectomy and laminectomy
      in the prone position. Anesthesia concerns included the risks of hemorrhage from
      the combined surgeries and upper airway edema from the prone position, and the
      physiologic changes of pregnancy. The surgeries proceeded without complication,
      and both mother and baby recovered uneventfully. CONCLUSION: With a
      multidisciplinary approach, two surgeries in two different positions with unique
      anesthetic considerations were performed safely under general anesthesia in
      advanced pregnancy in a parturient with cauda equina syndrome.

PMID- 17541078
TI  - Cadaveric ultrasound imaging for training in ultrasound-guided peripheral nerve
      blocks: lower extremity.

PMID- 17541079
TI  - Non-opioid strategies for acute pain management.
AB  - Subscribers to the Canadian Journal of Anesthesia are invited to read the
      following article to introduce them to a number of key articles cited in the
      bibliography. Reading at least the articles preceded by an asterisk (*) allows
      adequate preparation for the Self-Assessment Program, which can be completed by
      accessing the Continuing Medical Education (CME) link on the Journal site
      (http://www.cja-jca.org). Completion of the Self-Assessment Program will entitle
      subscribers to claim up to ten hours of Continuing Professional Development (CPD)
      under section 3 of CPD options, for a total of up to 20 Maintenance of
      Certification credits (note that section 3 hours are not limited to a maximum
      number of credits per five-year period). Obtaining CME credits for this module is
      not based upon attaining a specific score: the goal of participating is to define
      potential areas for improvement.

PMID- 17541080
TI  - Critical arrhythmia associated with pulmonary artery catheterization in a
      parturient with severe pulmonary hypertension.

PMID- 17541081
TI  - Angled or curved stylet for intubation with the GlideScope?

PMID- 17541082
TI  - Airway management for intra-oral surgery--airway first!

PMID- 17541083
TI  - Endotracheal intubation through a laryngeal mask/supraglottic airway.

PMID- 17541084
TI  - The Esophageal-Tracheal Combitube and esophageal injuries.

PMID- 17541085
TI  - A combined rigid videolaryngoscopy-flexible fibrescopy intubation technique under
      general anesthesia.

PMID- 17541087
TI  - Myths of MTAS and MMC.

PMID- 17541088
TI  - Changing disease patterns in South Asians in the UK.

PMID- 17541089
TI  - Population growth and the MDGs.

PMID- 17541090
TI  - Taking the lead against Reed Elsevier.

PMID- 17541091
TI  - The miracle at St Alfege's: seventy years on.

PMID- 17541092
TI  - Ankle brachial pressure index.

PMID- 17541093
TI  - Striving to recruit: the difficulties of conducting clinical research on elderly
      care home residents.

PMID- 17541094
TI  - Folter Arzt: interrogation of prisoners in Austria in 1773.

PMID- 17541095
TI  - Interrogation of prisoners after 2003: the role of health professionals.

PMID- 17541096
TI  - Bufale spotting, part three: assessing editorials.

PMID- 17541097
TI  - Sex and the nose: human pheromonal responses.
AB  - The chemosensory functions of the human nose are underappreciated. Traditional
      teaching is that the sense of smell detects volatile compounds, which may then
      allow the identification of substances that may be beneficial or harmful--such as
      good versus putrefied food. However, increasing evidence from research in other
      animals suggests that olfaction may serve another and more important purpose,
      that of mate selection in sexual reproduction; indeed, olfaction may be an
      essential impetus for evolution.

PMID- 17541098
TI  - Diabetes prevalence, process of care and outcomes in relation to practice size,
      caseload and deprivation: national cross-sectional study in primary care.
AB  - OBJECTIVE: To examine the association between practice list size, deprivation and
      the quality of care of patients with diabetes. DESIGN: Population-based cross
      sectional study using Quality and Outcomes Framework data. SETTING: England and
      Scotland. PARTICIPANTS: 55,522,778 patients and 8970 general practices with
      1,852,762 people with diabetes. INTERVENTIONS: None. MAIN OUTCOME MEASURES:
      Seventeen process and surrogate outcome measures of diabetes care. RESULTS: The
      prevalence of diabetes was 3.3%. Prevalence differed with practice list size and
      deprivation: smaller and more deprived practices had a higher mean prevalence
      than larger and more affluent practices (3.8% versus 2.8%). Practices with large
      patient list sizes had the highest quality of care scores, even after stratifying
      for deprivation. However, with the exception of retinal screening, peripheral
      pulses and neuropathy testing, differences in achievement between small and large
      practices were modest (<5%). Small practices performed nearly as well as the
      largest practices in achievement of intermediate outcome targets for HbA1c, blood
      pressure and cholesterol (smallest versus largest practices: 57.4% versus 58.7%;
      70.7% versus 70.7%; and 69.5% versus 72.7%, respectively). Deprivation had a
      negative effect on the achieved scores and this was more pronounced for smaller
      practices. CONCLUSION: Our study provides some evidence of a volume-outcome
      association in the management of diabetes in primary care; this appears most
      pronounced in deprived areas.

PMID- 17541099
TI  - A pain in the foot and a serious complication.

PMID- 17541101
TI  - AIDS: cures? Crisis!

PMID- 17541100
TI  - Joseph Asbury Bell and the birth of randomized trials.

PMID- 17541102
TI  - Disgust and psychiatric illness: have we remembered?
AB  - It has been argued that disgust has been forgotten by psychiatry. An overview of
      recent research on disgust is provided. Findings suggest that disgust is a
      predictor of the development of specific psychiatric conditions.

PMID- 17541103
TI  - Effects of antidepressant treatment following myocardial infarction.
AB  - BACKGROUND: Depression following myocardial infarction is associated with poor
      cardiac prognosis. It is unclear whether antidepressant treatment improves long
      term depression status and cardiac prognosis. AIMS: To evaluate the effects of
      antidepressant treatment compared with usual care in an effectiveness study.
      METHOD: In a multicentre randomised controlled trial, 2177 myocardial infarction
      patients were evaluated for ICD-10 depression and randomised to intervention
      (n=209) or care as usual (n=122). Both arms were evaluated at 18 months post
      myocardial infarction for long-term depression status and new cardiac events.
      RESULTS: No differences were observed between intervention and control groups in
      mean scores on the Beck Depression Inventory (11.0, s.d.=7.5 v.10.2, s.d.=5.1,
      P=0.45) or presence of ICD-10 depression (30.5 v. 32.1%, P=0.68). The cardiac
      event rate was 14% among the intervention group and 13% among controls (OR=1.07,
      95% CI 0.57-2.00). CONCLUSIONS: Antidepressant treatment did not alter long-term
      depression post-myocardial infarction status or improve cardiac prognosis.

PMID- 17541104
TI  - Does treating depression improve survival after acute coronary syndrome? Invited
      commentary on... Effects of antidepressant treatment following myocardial
      infarction.
AB  - Both the MIND-IT and the ENRICHD studies failed to show that medical outcomes of
      acute myocardial infarction can be improved by treating depression. However,
      neither study had sufficient statistical power to convincingly test this
      hypothesis. More effective treatments for depression will have to be developed if
      this hypothesis is to be tested with sufficient power in attainable samples.

PMID- 17541105
TI  - Length of gestation and depressive symptoms at age 60 years.
AB  - BACKGROUND: A non-optimal foetal environment, reflected in smaller birth size and
      shorter duration of gestation, is a risk factor for compromised health later in
      life. AIMS: To examine whether smaller birth size and shorter gestation predict
      depressive symptoms. METHOD: A total of 1371 members of a cohort born between
      1934 and 1944 at term (259-294 days'gestation) in Helsinki, Finland, completed
      the Beck Depression Inventory (BDI) and the Center for Epidemiological Studies
      Depression scale (CES-D) at an average age of 61.5 years (BDI) and 63.4 years
      (BDI and CES-D). RESULTS: Gestational length predicted depressive symptoms
      linearly and independently of gender and birth weight: per day decrease in
      gestational length, depressive symptoms scores increased by 0.8-0.9% (95% CI 0.2
      1.4, P<0.009). Weight, length and head circumference at birth showed no linear
      association with depression, adjusted for gender and gestational length. The
      results did not change when further controlled for socio-economic characteristics
      at birth and in adulthood, age and body mass index in adulthood. CONCLUSIONS:
      Susceptibility to depressive symptoms may relate to shorter length of gestation.

PMID- 17541106
TI  - Anxiety, post-traumatic stress disorder and depression in Korean War veterans 50
      years after the war.
AB  - BACKGROUND: There has been no comprehensive investigation of psychological health
      in Australia's Korean War veteran population, and few researchers are
      investigating the health of coalition Korean War veterans into old age. AIMS: To
      investigate the association between war service, anxiety, post-traumatic stress
      disorder (PTSD) and depression in Australia's 7525 surviving male Korean War
      veterans and a community comparison group. METHOD: A survey was conducted using a
      self-report postal questionnaire which included the PTSD Checklist, the Hospital
      Anxiety and Depression scale and the Combat Exposure Scale. RESULTS: Post
      traumatic stress disorder (OR 6.63, P<0.001), anxiety (OR 5.74, P<0.001) and
      depression (OR 5.45, P<0.001) were more prevalent in veterans than in the
      comparison group. These disorders were strongly associated with heavy combat and
      low rank. CONCLUSIONS: Effective intervention is necessary to reduce the
      considerable psychological morbidity experienced by Korean War veterans.
      Attention to risk factors and early intervention will be necessary to prevent
      similar long-term psychological morbidity in veterans of more recent conflicts.

PMID- 17541107
TI  - Explanations for the increase in mental health problems in UK reserve forces who
      have served in Iraq.
AB  - BACKGROUND: Deployment to the 2003 Iraq War was associated with ill health in
      reserve armed forces personnel. AIMS: To investigate reasons for the excess of
      ill health in reservists. METHOD: UK personnel who were deployed to the 2003 Iraq
      War completed a health survey about experiences on deployment to Iraq. Health
      status was measured using self-report of common mental disorders, post-traumatic
      stress disorder (PTSD), fatigue, physical symptoms and well-being. RESULTS:
      Reservists were older and of higher rank than the regular forces. They reported
      higher exposure to traumatic experiences, lower unit cohesion, more problems
      adjusting to homecoming and lower marital satisfaction. Most health outcomes
      could be explained by role, experience of traumatic events or unit cohesion in
      theatre. PTSD symptoms were the one exception and were paradoxically most
      powerfully affected by differences in problems at home rather than events in
      Iraq. CONCLUSIONS: The increased ill-health of reservists appears to be due to
      experiences on deployment and difficulties with homecoming.

PMID- 17541108
TI  - Genetic, environmental and gender influences on attachment disorder behaviours.
AB  - BACKGROUND: Despite current interest in attachment disorder, there is concern
      about its discrimination from other disorders and an unproven assumption of an
      environmental aetiology. AIMS: To test whether behaviours suggestive of
      attachment disorder are distinct from other childhood behavioural and emotional
      problems and are solely environmentally determined. METHOD: In a community sample
      of 13,472 twins, we carried out factor analysis of questionnaire items
      encompassing behaviours indicative of attachment disorder, conduct problems,
      hyperactivity and emotional difficulties. We used behavioural genetic model
      fitting analysis to explore the contribution of genes and environment. RESULTS:
      Factor analysis showed clear discrimination between behaviours suggestive of
      attachment disorder, conduct problems, hyperactivity and emotional problems.
      Behavioural genetics analysis suggested a strong genetic influence to attachment
      disorder behaviour, with males showing higher heritability. CONCLUSIONS:
      Behaviours suggestive of attachment disorder can be differentiated from common
      childhood emotional and behavioural problems and appear to be strongly
      genetically influenced, particularly in boys.

PMID- 17541109
TI  - Randomised controlled trial of interpersonal psychotherapy and cognitive
      behavioural therapy for depression.
AB  - BACKGROUND: Interpersonal psychotherapy and cognitive-behavioural therapy (CBT)
      are established as effective treatments for major depression. Controversy remains
      regarding their effectiveness for severe and melancholic depression. AIMS: To
      compare the efficacy of interpersonal psychotherapy and CBT in people receiving
      out-patient treatment for depression and to explore response in severe depression
      (Montgomery-Asberg Depression Rating Scale (MADRS) score above 30), and in
      melancholic depression. METHOD: Randomised clinical trial of 177 patients with a
      principal Axis I diagnosis of major depressive disorder receiving 16 weeks of
      therapy comprising 8-19 sessions. Primary outcome was improvement in MADRS score
      from baseline to end of treatment. RESULTS: There was no difference between the
      two psychotherapies in the sample as a whole, but CBT was more effective than
      interpersonal psychotherapy in severe depression, and the response was comparable
      with that for mild and moder-ate depression. Melancholia did not predict poor
      response to either psychotherapy. CONCLUSIONS: Both therapies are equally
      effective for depression but CBT may be preferred in severe depression.

PMID- 17541110
TI  - Temperament, character and personality disorders as predictors of response to
      interpersonal psychotherapy and cognitive-behavioural therapy for depression.
AB  - BACKGROUND: Interpersonal psychotherapy and cognitive-behavioural therapy are
      widely accepted as effective treatments for major depression. There is little
      evidence on how personality disorder or personality traits affect treatment
      response. AIMS: To determine whether personality disorder or traits have an
      adverse impact on treatment response to interpersonal psychotherapy or cognitive
      behavioural therapy in people receiving out-patient treatment for depression.
      METHOD: The study was a randomised trial in a university-based clinical research
      unit for out-patients with depression. RESULTS: Personality disorder did not
      adversely affect treatment response for patients with depression randomised to
      cognitive-behavioural therapy. Conversely, personality disorder did adversely
      affect treatment response for patients randomised to interpersonal psychotherapy.
      CONCLUSIONS: Despite the two therapies having comparable efficacy in patients
      with depression, response to interpersonal psychotherapy (but not cognitive
      behavioural therapy) is affected by personality traits. This could suggest the
      two therapies are indicated for different patients or that they work by different
      mechanisms.

PMID- 17541111
TI  - Comparison of outcomes following after-care from forensic and general adult
      psychiatric services.
AB  - BACKGROUND: Forensic psychiatry services are expanding in England and Wales but
      require support from general services for patient after-care. AIMS: To compare
      outcomes following community after-care from forensic or general adult psychiatry
      services. METHOD: An observational comparison was made of case management
      following discharge from medium security in seven pre-reorganisation health
      regions of England and Wales, by forensic services (n=409) and general adult
      services (n=652). Criminal convictions, hospital readmissions and deaths were
      compared over a mean follow-up period of 6.2 years, adjusting for difference in
      case mix. RESULTS: Forensic services did not supervise more high-risk patients in
      the community. Neither service was superior in outcome. More patients managed by
      general services died from natural causes. CONCLUSIONS: Neither service was
      superior on measures of subsequent offending or hospitalisation. Specialist
      forensic after-care conveyed no added benefit. Case management may have been the
      same in both services.

PMID- 17541112
TI  - Substance use in a population-based clinic sample of people with first-episode
      psychosis.
AB  - BACKGROUND: Substance use is implicated in the cause and course of psychosis.
      AIMS: To characterise substance and alcohol use in an epidemiologically
      representative treatment sample of people experiencing a first psychotic episode
      in south Cambridgeshire. METHOD: Current and lifetime substance use was recorded
      for 123 consecutive referrals to a specialist early intervention service.
      Substance use was compared with general population prevalence estimates from the
      British Crime Survey. RESULTS: Substance use among people with first-episode
      psychosis was twice that of the general population and was more common in men
      than women. Cannabis abuse was reported in 51% of patients (n=62) and alcohol
      abuse in 43% (n=53). More than half (n=68, 55%) had used Class A drugs, and 38%
      (n=43) reported polysubstance abuse. Age at first use of cannabis, cocaine,
      ecstasy and amphetamine was significantly associated with age at first psychotic
      symptom. CONCLUSIONS: Substance misuse is present in the majority of people with
      first-episode psychosis and has major implications for management. The
      association between age at first substance use and first psychotic symptoms has
      public health implications.

PMID- 17541113
TI  - Psychiatric disorders in Mexico: lifetime prevalence in a nationally
      representative sample.
AB  - BACKGROUND: No national data on lifetime prevalence and risk factors for DSM-IV
      psychiatric disorders are available in Mexico. AIMS: To present data on lifetime
      prevalence and projected lifetime risk, age at onset and demographic correlates
      of DSM-IV psychiatric disorders assessed in the Mexican National Comorbidity
      Survey. METHOD: The survey was based on a multistage area probability sample of
      non-institutionalised people aged 18-65 years in urban Mexico. The World Mental
      Health Survey version of the Composite International Diagnostic Interview was
      administered by lay interviewers. RESULTS: Of those surveyed, 26.1% had
      experienced at least one psychiatric disorder in their life and 36.4% of Mexicans
      will eventually experience one of these disorders. Half of the population who
      present with a psychiatric disorder do so by the age of 21 and younger cohorts
      are at greater risk for most disorders. CONCLUSIONS: Our results suggest an
      urgent need to re-evaluate the resources allocated for the detection and
      treatment of psychiatric illnesses in Mexico.

PMID- 17541114
TI  - Neurocognitive basis of insight in schizophrenia.
AB  - People with schizophrenia have been categorised into three groups: those with
      full insight (aware, correct attributers); those aware of being unwell, but who
      misattributed their symptoms (aware, incorrect attributers); and those unaware of
      being ill (unaware). Cluster analysis of 'awareness of illness'and 'relabelling
      of symptoms'scores on the Schedule for the Assessment of Insight confirmed three
      distinct subgroups. The unaware group were impaired on executive and memory
      tests, whereas those in the aware, misattributing group were cognitively intact.
      Findings support an association between unawareness of illness and executive
      dysfunction, and highlight the separation of symptom misattribution from
      unawareness of illness.

PMID- 17541115
TI  - Short-term antidepressant treatment and facial processing. Functional magnetic
      resonance imaging study.
AB  - We used functional magnetic resonance imaging to investigate the effects of short
      term treatment with reboxetine, a selective noradrenaline reuptake inhibitor, on
      emotional facial processing in healthy volunteers. Reboxetine was associated with
      a reduced amygdala response to fearful faces and increased activation to happy v.
      neutral facial expressions in the right fusiform gyrus, relative to placebo
      treatment and in the absence of changes in mood. Our results show that reboxetine
      modulates the neural substrates of emotional processing, highlighting a mechanism
      by which drug treatment could normalise negative bias in depression and anxiety.

PMID- 17541116
TI  - Adjunctive fast repetitive transcranial magnetic stimulation in depression.
AB  - The place of repetitive transcranial magnetic stimulation (rTMS) in the treatment
      of depression remains unclear. In this sham-controlled study we determined the
      efficacy and acceptability offast, left frontal rTMS given three times a week
      over 4-6 weeks to 29 patients with depression (79% treatment-resistant). The
      procedure was generally well tolerated and more effective than sham treatment (55
      v.77% responding, P<0.05), with improvement maintained to 12 weeks. This therapy
      could be a useful addition to available treatments but further research is needed
      to determine the optimum treatment parameters.

PMID- 17541117
TI  - Perceived stigma and depression among caregivers of patients with bipolar
      disorder.
AB  - This study investigates the associations between perceived stigma, depressive
      symptoms and coping among caregivers of people with bipolar disorder. Caregivers
      of 500 people with DSM-IV bipolar disorder responded to measures of these
      constructs at study entry. Patients' clinical and functional status were
      evaluated within 30 days of the caregiver assessment. Perceived stigma was
      positively associated with caregiver depressive symptoms, controlling for patient
      status and socio-demographic factors. Social support and avoidance coping
      accounted for 63% of the relationship between caregiver stigma and depression.
      Results suggest that caregivers' perceptions of stigma may negatively affect
      their mental health by reducing their coping effectiveness.

PMID- 17541118
TI  - Intensive case management: targeted population as important as case-load size.

PMID- 17541120
TI  - Problems in diagnosing bipolar disorder.

PMID- 17541122
TI  - Comparison of nonuniform strut distribution between two drug-eluting stent
      platforms.
AB  - OBJECTIVE: To compare the difference of strut distribution between two clinically
      available drug-eluting stent platforms (Bx Velocity and Express II stents) using
      intravascular ultrasound (IVUS). BACKGROUND: Nonuniform strut distribution (NSD)
      has been shown to be associated with increased intimal hyperplasia after drug
      eluting stent implantation. METHODS: IVUS imaging was performed on Bx Velocity (n
      = 6) and Express II stents (n = 6) after inflation pressures of 10, 16, and 26
      atm in a bench test model. Percent NSD was defined as the length of segments with
      NSD (interstrut angle > 90 degrees) divided by stent length. NSD was also
      assessed in postprocedure IVUS images in 53 clinical cases (32 Cypher, 21 Taxus)
      using 3-dimensional IVUS analysis. RESULTS: Frequency of NSD segment and %NSD
      were lower in Bx Velocity stents than in Express II stents at the inflation
      pressures of 16 and 26 atm (%NSD: 16 atm, 0% vs. 13.8 +/- 9.4%; p < 0.005; 26
      atm, 1.1 +/- 2.6% vs. 19.9 +/- 6.9% p < 0.0001). In postprocedural images from
      clinical cases, the frequency of NSD segment and %NSD were lower in Cypher stents
      than in Taxus stents (%NSD: 0.5 +/- 1.6 vs. 6.8 +/- 7.2; p < 0.0001). CONCLUSION:
      NSD segment was observed less in Bx Velocity stents than in Express II stents.

PMID- 17541123
TI  - Feasibility study of percutaneous transvalvular endomyocardial cryoablation for
      the treatment of hypertrophic obstructive cardiomyopathy.
AB  - BACKGROUND: Left ventricular outflow tract (LVOT) obstruction in the setting of
      hypertrophic cardiomyopathy (HCM) confers negative adverse outcomes. Current
      nonpharmacologic treatment options include surgical myectomy and percutaneous
      transcoronary ablation of septal hypertrophy (TASH). While TASH negates a more
      invasive procedure, concern remains with particular regard to the arrhythmogenic
      potential of the resultant myocardial scar. Percutaneous transvalvular
      endomyocardial septal cryoablation (PTESC) may circumvent some of these potential
      limitations and offer a novel treatment strategy. OBJECTIVES: The purpose of this
      study was to report our early experience and outcomes with percutaneous
      endomyocardial cryoablation of the interventricular septum in obstructive HCM.
      METHODS AND RESULTS: Between March 2005 and May 2006, 3 patients (2 male, 1
      female) with symptomatic obstructive HCM underwent PTESC. Basal LVOT gradients
      measured during left heart catheterization were 70, 126 and 100 mmHg for Patients
      1, 2 and 3, respectively. Using 7 Fr and 9 Fr 8 mm tip CryoCath Freezor catheters
      (CryoCath Technologies, Inc., Montreal, Quebec, Canada), cryothermal energy was
      applied to the interventricular septum under fluoroscopic guidance. A total of 20
      to 32 applications of cryothermal energy were delivered, with the mean nadir
      temperature sustained during cryoablation being -88 degrees Celcius. Two of the 3
      patients had an immediate reduction in the LVOT gradient. However, at 6 months,
      only 1 patient had a significant sustained reduction in LVOT gradient. No adverse
      events relating to the procedure were experienced. CONCLUSION: PTESC is feasible,
      but did not result in a significant, sustained reduction in LVOT gradient in 2 of
      the 3 patients in this small series of obstructive HCM patients. The technique
      warrants further study to improve the consistency and duration of reduction in
      outflow gradient.

PMID- 17541124
TI  - Analysis of left and right ventricular Doppler tissue imaging in patients
      undergoing percutaneous closure of patent foramen ovale.
AB  - Percutaneous patent foramen ovale (PFO) closure is performed for the prevention
      of paradoxical emboli. Doppler tissue imaging (DTI) was performed before and
      following transcatheter PFO closure in patients with an otherwise structurally
      normal heart to detect alterations in regional myocardial motion. The analysis
      revealed a mild, but statistically significant, reduction in the systolic motion
      of the basal interventricular septum. Other DTI parameters, including diastolic
      motion of the basal interventricular septum, systolic and diastolic motion of the
      left ventricular free-wall mitral annulus junction and the right ventricular free
      wall tricuspid annulus junction, and the left ventricular cardiac performance
      (Tei) index remained unchanged. We found, thus, that transcatheter PFO closure
      does not cause major alteration in regional myocardial motion or cardiac
      performance.

PMID- 17541125
TI  - Cardiac function after percutaneous closure of patent foramen ovale.

PMID- 17541126
TI  - Interatrial septal defect closure for prevention of cerebrovascular accidents:
      impact on recurrence and frequency of migraine headaches.
AB  - BACKGROUND: Recent data suggest that percutaneous closure of interatrial septal
      defect (IASD) is associated with a reduction in the intensity, frequency and
      duration of migraine headaches. In this study we review our own data to determine
      if we can reproduce the relationship between IASD closure in patients with a
      history of a central nervous system event (stroke or a transient ischemic attack
      [TIA]) and migraine headaches (HA). METHODS: Fifty-eight consecutive patients
      with a history of unexplainable stroke or TIA with the exception of the presence
      of an IASD were included in this retrospective study. Multiple variables were
      collected including age, gender, history of smoking, hypertension, diabetes,
      hypercholesterolemia, ejection fraction, anticoagulant use pre- and
      postprocedure, shunt grade across the IASD pre- and postprocedure, defect size
      and right-sided filling pressures. All patients with a history of migraine HA
      answered the Migraine Disability Assessment Test (MIDAS), a standardized migraine
      questionnaire. Descriptive analysis was performed on all variables and compared
      among migraine and nonmigraine HA patients. Pre and post closure intensity and
      frequency of migraine HA were compared. RESULTS: Of 58 patients, 14 (24.14%) had
      migraine HAs prior to percutaneous closure. There were no significant differences
      among the migraine and nonmigraine HA groups except that the migraine HA
      sufferers were younger (p = 0.016). One patient with migraine HA died on follow
      up from complications of cardiomyopathy. Only 5 (38.5%) of 13 patients reported
      still having migraine HA post closure of IASD. The frequency (41.6 +/- 36.4 vs.
      9.3 +/- 24.8; p = 0.005) and intensity (8.0 +/- 1.9 vs. 2.1 +/- 3.2; p = 0.001)
      of the migraine HAs were markedly reduced post closure at 759 +/- 545.6 days
      (range 89 to 1,433 days). There was no relationship between the shunt grade and
      the frequency or intensity of migraine HA. CONCLUSION: We conclude that IASD
      closure in patients with history of migraine HA and stroke or TIA have a marked
      improvement in the frequency and intensity of their HA. Migraine HA resolved in
      61.54% patients post closure. Larger randomized studies are needed to confirm
      these findings, which could have significant implications for sufferers of
      migraine HA.

PMID- 17541127
TI  - Recurrent in-stent restenosis is not associated with the angiotensin-converting
      enzyme D/I, angiotensinogen Thr174Met and Met235Thr, and the angiotensin-II
      receptor 1 A1166C polymorphism.
AB  - Although great progress has been made in reducing renarrowing of the lumen after
      stenting of coronary arteries, a considerable number of patients develop
      recurrent in-stent stenosis. Several studies suggest that neointimal
      proliferation is the crucial pathophysiological process underlying restenosis
      after stenting. The renin-angiotensin-aldosterone system (RAS) has been
      implicated in the development of neointimal hyperplasia. We tested the hypothesis
      that polymorphisms of the RAS genes are associated with recurrent in-stent
      restenosis (ISR). Coronary stent implantation was performed in 272 patients with
      clinical symptoms or objective signs of ischemia. At follow-up angiography 6
      months after stenting, 81 patients (29.8%) revealed in-stent restenosis. These
      patients underwent balloon angioplasty and were scheduled for a further 6 months
      of follow up. One year after initial stenting of the coronary artery, 39 patients
      displayed no significant angiographic ISR, whereas 42 patients developed
      recurrent in-stent restenosis (RISR). The survey of specific functional
      polymorphisms of the RAS, namely the angiotensin-I converting enzyme (ACE) D/I,
      the angiotensinogen (AGT) T174M and M235T, and A1166C of the angiotensin-II
      receptor 1 (AGTR1), revealed that the incidence RISR in the high-risk cohort was
      not associated with any of the polymorphisms examined in this study.

PMID- 17541128
TI  - Persistent sex difference in hospital outcome following percutaneous coronary
      intervention: results from the New York State reporting system.
AB  - BACKGROUND: Although sex-related differences in early outcomes have been observed
      in young women following acute myocardial infarction (AMI) and coronary bypass
      surgery, evidence for similar differences following percutaneous coronary
      intervention (PCI) is lacking. METHODS: Using the 1999 to 2002 New York State PCI
      reporting system, we identified 11,162 men and 2,561 women aged 50 years or
      younger undergoing a first PCI procedure. In-hospital outcomes were compared by
      gender after multivariable adjustment for baseline, clinical and procedural
      characteristics. RESULTS: Young women undergoing an initial PCI procedure were
      more likely to belong to racial or ethnic minorities and exhibit more
      comorbidities than young men. However, they had better ejection fraction (52.9%
      +/- 11.3 vs. 51.9 +/- 11; p = 0.0002) and presented more often with single-vessel
      disease (75% vs. 67%; p < 0.0001). Despite women receiving glycoprotein IIb/IIIa
      inhibitors (58.6% vs. 65.1%; p < 0.0001) and stents (92.5% vs. 94.9%; p < 0.0001)
      less often, procedural success was achieved equally (97% vs. 96%). Young women
      experienced higher rates of in-hospital mortality (0.70% vs. 0.22%; p < 0.0001),
      and vascular damage (0.82% vs. 0.24%; p < 0.0001) compared to men. In
      multivariable analysis, female sex independently predicted in-hospital mortality
      (OR 4.0, 95% CI: 1.9 to 8.1) after adjustment for urgency of PCI, clinical and
      procedural characteristics. CONCLUSION: A gender-based difference in early
      survival exists in young women undergoing a first PCI procedure. Further
      investigation into the mechanism of this higher risk is warranted.

PMID- 17541129
TI  - Platelet-derived growth factor receptor antagonist STI571 (imatinib mesylate)
      inhibits human vascular smooth muscle proliferation and migration in vitro but
      not in vivo.
AB  - BACKGROUND: Cell-specific inhibition of vascular smooth muscle cells, the primary
      constituent of neointima following arterial injury, without deleterious effects
      on vascular endothelial cell function may be a critical requirement for drug
      eluting stents that are not prone to excess late thrombosis. We hypothesized that
      imatinib mesylate (Gleevec, Glivec, formerly known as STI571), a relatively
      selective inhibitor of protein tyrosine kinases including platelet-derived growth
      factor receptor (PDGFR), would inhibit hCASMC proliferation and migration in
      vitro with little effect on endothelial cell proliferation and prevent restenosis
      in a swine balloon injury model. METHODS: Proliferation and migration of
      stimulated human vascular smooth muscle and endothelial cells were quantified in
      cell culture in the presence of imatinib (0.001 to 10 M). Imatinib-loaded drug
      eluting stents were implanted in swine coronary arteries after predilatation with
      an oversized balloon, and neointimal proliferation was measured by quantitative
      angiography and histopathology. RESULTS: Increasing doses of imatinib-inhibited
      autophosphorylation of the PDGFR and its downstream effects of proliferation and
      migration of human CASMC in a dose-responsive manner, yet had no effect on
      stimulated human aortic endothelial cells. However, imatinib-eluting stents had
      no effect on neointimal proliferation and restenosis in a standard porcine in
      stent restenosis model compared to bare-metal or unloaded polymer-coated stents.
      CONCLUSION: We conclude that imatinib is a potent inhibitor of proliferation and
      migration of human vascular smooth muscle cells in vitro, but has no effect on
      human vascular endothelial cell proliferation. However, the lack of an in vivo
      effect on neointimal proliferation in a standard porcine coronary overstretch
      model does not support the use of imatinib mesylate for localized drug delivery
      in the prevention of in-stent restenosis.

PMID- 17541130
TI  - Carotid artery in-stent restenosis in a patient with contralateral total
      occlusion, resolved with drug-eluting stenting.
AB  - A 70-year-old male patient with 90% stenosis of the right carotid artery and
      total occlusion of the left carotid artery underwent right carotid stenting. Two
      weeks after the procedure, the patient experienced grand mal seizures, and had
      angioplasty after 6 and 11 months, respectively, for recurrent in-stent
      restenosis. During drug-eluting stent deployment, the patient developed acute
      stent thrombosis, but he recovered quickly and completely after local
      thrombolysis and balloon angioplasty. For the 1 year of follow up to date, the
      patient has been symptom-free and without restenosis. At 6 months from the last
      mentioned study, the patient was admitted for intermittent claudication,
      fatigability and severe hypertension. A Doppler study of the carotid stent showed
      normal velocities, and the the neurological exam was similar to the previous one.
      Angiography confirmed bilateral ostial stenosis of the renal arteries and we
      performed bilateral renal stenting at that time.

PMID- 17541131
TI  - Spontaneous right coronary artery dissection: evaluation by 64-slice
      multidetector computed tomographic angiography.

PMID- 17541132
TI  - Aneurysm of the Vieussens' arterial ring.

PMID- 17541134
TI  - Trifurcating coronary artery disease: expanding the frontier of interventional
      cardiology.

PMID- 17541135
TI  - The Pronto catheter: distal embolization of any remaining thrombus fragments may
      be a risk of creating and then removing negative pressure.

PMID- 17541136
TI  - Successful crossing of an angulated lesion using a new deflectable-tip guidewire
      (Steer-IT).
AB  - Tortuous or highly angulated vessels can sometimes be a hindrance to successful
      percutaneous coronary intervention while conferring an increased risk of major
      adverse events compared to lesions in nonangulated vessels. We present a case
      demonstrating the benefit of a recently available deflecting tip 0.014 inch
      guidewire to help negotiate an acute-angled takeoff of the left anterior
      descending artery from the left main coronary artery. This novel device proved
      successful, and as such, can complement the armamentarium of the modern-day
      interventionalist.

PMID- 17541137
TI  - Subclavian-vertebral artery bifurcation stenting using drug-eluting stents: a
      report of two cases using different techniques.
AB  - Endovascular treatment of vertebral artery stenosis and subclavian artery
      stenosis are low-risk procedures, but there are few reports of the best approach
      for subclavian-vertebral artery stenoses where there is an ostial stenosis of a
      vertebral artery that arises from a stenosed segment of the subclavian artery.
      This is a report of two cases with subclavian-vertebral artery stenosis that were
      treated with two different techniques. One-year follow up demonstrated widely
      patent stents. Also, to our knowledge, this is the first report of the use of the
      crush-stenting technique using drug-eluting stents in subclavian-vertebral artery
      bifurcation lesions.

PMID- 17541138
TI  - Old technique, new use: novel use of a buddy wire to deploy a detached stent.
AB  - Stent dislodgement or loss in a coronary artery carries significant risks of
      infarction, thrombosis and requirement for emergency bypass surgery. Even with
      the advent of premounted stents, stent loss can occasionally occur, especially
      when performing intervention in calcified and tortuous anatomy. Multiple stent
      retrieval/stent exclusion techniques have been described to overcome this dreaded
      complication. We describe the first case of deploying a dislodged stent using a
      buddy wire technique with both wires through the center of the dislodged stent,
      and subsequent use of the small balloon technique to successfully deploy a
      dislodged stent in a heavily calcified and tortuous circumflex artery.

PMID- 17541139
TI  - Thrombosis and acute myocardial infarction as consequences of very late stent
      malapposition after implantation of a drug-eluting stent.
AB  - The use of drug-eluting stents (DES) provides early and late benefits
      demonstrated by angiographic and clinical outcomes. Here we report a case of late
      stent thrombosis and acute myocardial infarction caused by late stent
      malapposition (LSM) of a DES at 16 months after the procedure. We successfully
      treated the patient with balloon angioplasty after intravenous thrombolytic
      therapy. This case illustrates that a LSM can develop at any time after DES
      implantation and can result in acute coronary syndrome. Therefore, clinicians
      should be aware of the possibility of late cardiac events after implantation of
      DES.

PMID- 17541140
TI  - Spontaneous coronary artery dissection in a woman with depression without
      coronary atherosclerotic risk factors.

PMID- 17541141
TI  - Transcatheter closure of ruptured sinus of Valsalva aneurysm using the Amplatzer
      duct occluder in a critically ill post-CABG patient.
AB  - Ruptured sinus of Valsalva aneurysm is a rare but well recognized clinical
      entity. These patients develop congestive heart failure due to biventricular
      increases in volume as a result of sudden aortocardiac shunting. Traditionally,
      surgical repair has been the mainstay of therapy. We report a case of a ruptured
      sinus of Valsalva aneurysm that was successfully closed percutaneously using the
      Amplatzer duct occluder in a critically ill patient operated on previously for
      coronary artery disease and presenting with acute congestive heart failure.

PMID- 17541142
TI  - The use of both peripheral and coronary techniques to treat a diseased saphenous
      vein graft.
AB  - This report describes the simultaneous use of both peripheral and coronary distal
      protection techniques to prevent no-reflow phenomena in a large sequential
      saphenous vein graft. The use of a large peripheral stent allowed for
      simultaneous distal protection while advancing the larger-lumen stent over both
      wires, resulting in safe deployment.

PMID- 17541143
TI  - Spontaneous coronary artery dissection related to menstruation.
AB  - We present the case of a young woman who developed an acute onset of classic
      cardiac symptoms, but because of her age and lack of risk factors, had a
      significant delay in transfer for cardiac catheterization. She was found to have
      spontaneous dissection of the left coronary system, eventually requiring emergent
      bypass surgery. The patient had recently began her menstrual period, and we
      speculate that hormonal fluctuations contributed to this process. The role of
      hormonal influences on the coronary vasculature is not entirely understood, but
      the incidence of spontaneous coronary dissection is higher in women, and is
      usually related to changes in hormones such as pregnancy and oral contraceptive
      use. We review the literature on spontaneous coronary dissection, the influence
      of hormones on the vasculature, as well as diagnosis and treatment options.

PMID- 17541144
TI  - [Chronic obstructive lung disease: the hidden epidemic].

PMID- 17541145
TI  - [Social insurance certificate for medication].

PMID- 17541146
TI  - [Prevalence of COPD in Iceland--the BOLD study].
AB  - OBJECTIVE: To investigate the prevalence of chronic obstructive pulmonary disease
      (COPD) in Iceland and possible risk factors. MATERIALS AND METHODS: This
      Icelandic survey is a part of an international study (www.BOLDCOPD.org). The
      target population consisted of a simple random sample taken among all non
      institutionalized Icelanders 40 years and older living in Reykjavik and adjacent
      suburbs (n=938). Participants were subjected to a structured interview based on
      questionnaires on respiratory diseases, symptoms, life style and possible risk
      factors. They also underwent a spirometry that was repeated after inhalation of a
      bronchodilating agent. COPD stage I, or higher, was defined according to the GOLD
      staging (www.goldcopd.org) based on chronic airflow limitation (FEV1/FVC 70%)
      persisting after inhaled bronchodilator. RESULTS: Full participation was by 755
      (80.5%). Altogether 18.0 % of the participants fulfilled criteria for COPD, GOLD
      stage I or higher and 9.0 % for GOLD stage II or higher. There were
      proportionally more young females (40-49 years) than males diagnosed with COPD
      GOLD stage I or higher (8.1% compared to 4.8%), even though there was no
      difference in total prevalence between males and females. The prevalence of COPD
      increased with increasing age and the amount of tobacco smoked. Only a part of
      those fulfilling criteria for COPD had been diagnosed by doctors. CONCLUSION: Our
      results show a high prevalence of COPD among Icelanders 40 years and older when
      internationally accepted criteria and methods are used. These results are useful
      for heath authorities when planning and giving priority in our future health care
      system.

PMID- 17541147
TI  - [Actinomycosis in a 70 year old woman with a forgotten intrauterine contraceptive
      device].
AB  - Actinomycosis is an infectious disease that has been known since the late
      nineteenth century. In the pre-antibiotic era it was thought to be rather common
      but with increased use of antimicrobial agents its incidence has decreased
      significantly. The causative agent, most commonly Actinomyces israelii, is part
      of the commensal bacterial flora. It can infect any tissue, respects no tissue
      boundaries and can spread throughout the body. The clinical presentation of this
      illness can be similar to malignant disease and definite diagnosis is sometimes
      not apparent until after surgery and histologic examination. We report the case
      of a 71 year old woman who suffered from actinomycosis of the uterus and ovaries
      due to a forgotten intrauterine contraceptive device that had been in place for
      over four decades. The disease presentation was consistent with malignant disease
      and tumor markers, CA 125, CA 19-9 and CEA, measured in blood were elevated. She
      was treated successfully with total hysterectomy and bilateral salphingo
      oophorectomy, as well as penicillin for six months.

PMID- 17541148
TI  - [Spontaneous intracranial hypotension--a case report and discussion].
AB  - Thirty-three year old woman came to the emergency room with 3 days' history of
      worsening headache which was relieved by lying down. Examination was normal.
      Magnetic Resonance Imaging (MRI) of the head showed an enhancement of the
      meninges. No pressure could be measured during lumbar puncture and cerebrospinal
      fluid (CSF) was obtained by elevating the patient's head. There was an elevation
      of protein in the CSF without signs of infection or inflammation. Computerised
      tomography (CT) myelogram showed a prominent leak from the 2nd right cervical
      nerve sheath. A blood patch was done at this level with some improvement of
      symptoms. The patient was readmitted four days later as the headache had
      worsened. A blood patch was repeated at the same level with limited results.
      Therefore a fibrinogen patch was done at the same level, of which the effect
      lasted only 24 hours. A repeated CT myelogram showed a leak from the left 8th
      cervical and 1st thoracic nerve sheets, but not from the 2nd right cervical nerve
      sheath. Blood and fibrinogen patches were done at these levels repeatedly with
      limited results. Therefore, a MRI of cervical-thoracic spine was done which
      showed signs of previous blood patch at the 1st left thoracic nerve sheath but no
      sign of a patch over the 8th left cervical nerve sheath. A fibrinogen patch was
      done at this level. The patient became symptom free and was finally discharged
      home. We present a case of complicated spontaneous intracranial hypotension and
      review of the literature.

PMID- 17541149
TI  - Exploring unique structures: flexibility is a significant factor in biological
      activity.
AB  - The effect of molecular flexibility on biological activity was described for soft
      (e.g. hGH peptides) and hard molecules (e.g. biscoclaurine-type alkaloids). These
      molecules had a macrocyclic structure during molecular mechanics analysis, and
      the minimum essential unit, which affects insulin-involved fatty acid synthesis,
      was observed. The flexibility of the molecular center is concerning with
      biological activity through the diversification of structural feature, and
      compared with two types of molecules which have a rigid (haloacetylcarbamoyl-2
      nitroimidazole analogs: chiral-TXs) or flexible (bis-quaternary ammonium
      compounds: bis-QACs) molecular center. Center flexibility reflected the
      conformation occurrence in TXs and bis-QACs. A parameter (solvation-free energy:
      dGW), which reflects structural hydrophobicity, was shown, and applied to the
      molecular design of brefeldin A analog. This hydrophobic index was very useful,
      and was used for conformational analysis of chiral-TXs and bis-QACs. In molecular
      dynamics analysis of cholesterol-dependent cytolysin (e.g. streptolysin O) and 
      independent cytolysin (e.g. intermedilysin), whole molecules moved like a bow and
      different conformations were shown in every moment. In such situations, the
      membrane-associated 11mer region in these cytolysins were flexible and could
      always interact with extramolecular factors (e.g. membrane constitution).

PMID- 17541150
TI  - Anti-inflammatory effect of oyaksungisan in peripheral blood mononuclear cells
      from cerebral infarction patients.
AB  - Oyaksungisan, the herbal prescription composed of eleven herbs, has been widely
      used in treatment of cerebral infarct in Oriental Medicine. However, the
      mechanisms by which the herbal formula affects on the production of pro- and anti
      inflammatory cytokines in cerebral infarction patients remain unknown yet. The
      secretory levels of pro-inflammatory cytokines, including tumor necrosis factor
      (TNF)-alpha, interleukin (IL)-1beta, and IL-6, and IL-10 were significantly
      increased in both LPS and PHA-stimulated peripheral blood mononuclear cells
      (PBMCs) from cerebral infarction patients. However, pretreatment with
      oyaksungisan significantly inhibited the secretion of pro- and anti-inflammatory
      in PBMCs. Also, oyaksungisan induced a significant increase of transforming
      growth factor (TGF)-beta1 in PBMCs. Thus, these data indicate that oyaksungisan
      may be beneficial in the cessation of inflammatory processes of cerebral infarct
      through suppression of TNF-alpha, IL-1beta, IL-6, and IL-10 and induction of TGF
      beta1.

PMID- 17541151
TI  - Effects of keishibukuryogan on vascular function in adjuvant-induced arthritis
      rats.
AB  - It is known that rheumatoid arthritis (RA) accelerates atherosclerosis. Further,
      the soluble form of vascular adhesion molecule-1 (VCAM-1) is known as a
      predictive marker of atherosclerosis in RA patients. We reported that
      keishibukuryogan, one of the Kampo formulas, improved articular symptoms and
      decreased soluble VCAM-1 in patients with RA. In adjuvant-induced arthritis (AIA)
      rats, an animal model of RA, it is known that endothelial function is injured by
      inflammation. So, we investigated the effect of keishibukuryogan on endothelial
      function in AIA rats. Lewis rats were divided into control, AIA control, and AIA
      with keishibukuryogan groups. The AIA with keishibukuryogan group was fed 3%
      keishibukuryogan contained in normal chow. On day 25 after injection of
      Mycobacterium butyricum, endothelium-dependent relaxation by acetylcholine in the
      AIA control group was suppressed, but it was improved in the AIA with
      keishibukuryogan group. The contractions by xanthine/xanthine oxidase in both AIA
      rats increased, but that in keishibukuryogan decreased compared to the AIA
      control group. Plasma levels of lipid peroxide increased in the AIA control
      group, but keishibukuryogan decreased these levels. Plasma levels of nitric oxide
      (NO) increased in both AIA groups. The expressions of endothelial NO synthase,
      inducible NO synthase and VCAM-1 of thoracic aorta were investigated by western
      blotting. These expressions increased in the AIA control group, but were
      restricted in the AIA with keishibukuryogan group. We considered that
      keishibukuryogan protected the endothelial function of AIA rats mainly by its
      anti-oxidative effect.

PMID- 17541152
TI  - In vivo effects of oral contraceptives on paraoxonase, catalase and carbonic
      anhydrase enzyme activities on mouse.
AB  - Many effects that oestrogens and progestrogens used in oral contraceptive (OC)
      have on enzyme physiology are of importance on homeostasis. This study was
      carried out in order to determine the in vivo effect of three oral contraceptives
      containing ethinyl estradiol in combination with desogestrel and levonorgestrel
      on the paraoxonase (PON), catalase (CAT) and carbonic anhydrase (CA) activities
      in mice, which are model organisms for humans. Serum and liver paraoxonase
      activities were determined spectrophotometrically by using paraoxan as a
      substrate according to the methods of Gan et al. and Gil et al., respectively.
      Catalase and carbonic anhydrase activities were determined from erythrocytes used
      Aebi and Maren methods, respectively. For these studies, a group of ten mice
      (25+/-2 g) was selected for oral administration for 21 d of each drug (0.15 mg
      desogestrel+0.03 mg ethinylestradiol (A); 0.15 mg levanogestrel+0.03 mg
      ethinylestradiol (B) and 0.15 mg desogestrel+0.02 mg ethinylestradiol (C)). A
      group of ten mice was included in the study for a control group, which were not
      subject to drug administration. For each drug, a mean of the serum and liver
      paraoxonase activity and erythrocytes catalase and carbonic anhydrase activities
      were determined and compared to the control groups. While mouse liver PON
      activity showed a statistically significant decrease for all three drugs, serum
      PON activity increased. Erythrocytes catalase activity was significantly
      decreased by all contraceptives used. On the other hand, these contraceptives did
      not change the erythrocytes carbonic anhydrase activity.

PMID- 17541153
TI  - Antimelanogenic and antioxidant properties of gallic acid.
AB  - To find novel skin-whitening agents, the melanogenesis inhibitory action of
      gallic acid (GA) was investigated. In this current study, the effects of GA on
      mushroom tyrosinase, tyrosinase inhibitory activity, and melanin content were
      assessed in B16 melanoma cells (B16 cells). Results indicated that GA has a
      strong antityrosinase activity (IC50=3.59x10(-6) M). Furthermore, data on murine
      tyrosinase activity and melanin biosynthesis revealed that GA effectively
      suppressed murine tyrosinase action and the amount of melanin. To investigate the
      relation between GA's inhibition of melanogenesis and antioxidant activity, the
      effect of GA on reactive species (RS) generation and the reduced glutathione
      (GSH)/oxidized glutathione (GSSG) ratio in were determined in B16 cells. Results
      indicated that GA effectively down-regulated the RS generation and enhanced the
      GSH/GSSG ratio. Based on these results, I propose that GA exerts antimelanogenic
      activity coupled with antioxidant properties by suppressing RS generation and
      maintaining a higher GSH/GSSG ratio.

PMID- 17541154
TI  - Characterization and identification of a steroid receptor-binding protein, SRB
      RGS.
AB  - We cloned the cDNA of a novel steroid receptor-binding protein, SRB-RGS, which
      suppressed the estrogen receptor (ER)alpha-mediated and other promoter-driven
      transcriptional activities. This study revealed the interaction between the full
      length SRB-RGS and full-length ERalpha or ERbeta by a coimmunoprecipitation
      assay. The full-length SRB-RGS and full-length ERalpha interacted in COS-7 cell
      by a mammalian two-hybrid system. The interaction between intrinsic SRB-RGS and
      ERs in the nuclear ER extract from the rat uteri was observed by the gel-shift
      assay. These results strongly suggested that SRB-RGS interacts with ERs bound to
      DNA (estrogen response element) in the nuclei of the cells. SRB-RGS suppressed
      very efficiently the ERalpha-, ERbeta-, and ERalpha+ERbeta-mediated
      transcriptional activities. Green fluorescence of enhanced green fluorescence
      protein (EGFP)-tagged SRB-RGS was localized both in the nucleus and in the
      cytoplasm. Intrinsic SRB-RGS was immunostained in the nucleus and the cytoplasm
      of HeLa cells. The putative SRB-RGS deduced from cDNA sequence was identified by
      the immunostaining and Western blotting by using the anti-SRB-RGS antibody.
      Overexpression of SRB-RGS induced the cell death in the HeLa cells. The
      nucleotide sequence of SRB-RGS cDNA that we cloned previously is identical with
      that of the newly isolated RGS3 cDNA. SRB-RGS could interact with ERs bound DNA
      in the nuclei of the cells and suppressed the ERs-mediated transcriptional
      activities.

PMID- 17541155
TI  - Knock-down of sorcin induces up-regulation of MDR1 in HeLa cells.
AB  - In our previous study, the MDR1/Pglycoprotein-overexpressing multidrug resistant
      subline, Hvr100-6, was established from the human cervical carcinoma cell line
      HeLa-Ohio (HeLa) by stepwise exposure to an anti-microtubule agent, vinblastine
      sulfate, a typical substrate of MDR1. Their gene and protein expression profiles
      were analyzed herein, and 148 genes were identified to be differentially
      expressed by cDNA microarray analysis. The up-regulation of sorcin, a soluble
      resistance-related calcium-binding protein of 22 kDa, was confirmed in Hvr100-6
      cells by the proteome analysis. To clarify the relationship between MDR1 and
      sorcin, HeLa cells were treated with small interfering RNAs (siRNAs) targeted for
      theirs mRNAs. The siRNA for MDR1 mRNA resulted in its decrease by 86% and 61% on
      the days 1 and 2 after the treatment, whereas the expression level of sorcin mRNA
      was not changed. On the other hand, the siRNA for sorcin mRNA suppressed its
      expression by 80-90% on days 1-3 after the treatment. Interestingly; suppression
      of sorcin induced a more than 3-fold increase in the expression level for MDR1
      mRNA. An efflux function of MDR1 evaluated with using rhodamine 123 as a probe
      showed a tendency to be increased in HeLa cells treated with siRNA for sorcin,
      compared with that in the cells treated with scramble siRNA. The activity and the
      expression of caspase-3 in the sorcin knock-down HeLa cells were relatively
      higher than those in the cells treated with scramble siRNA. Thus, we demonstrated
      that sorcin might be a partial suppressor of MDR1 expression. Furthermore, the
      present study suggested that sorcin repressed apoptosis via dysfunction of
      caspase-3.

PMID- 17541156
TI  - The chemopreventive effect of taxifolin is exerted through ARE-dependent gene
      regulation.
AB  - Phase II detoxification enzymes are responsible for the detoxification and
      elimination of activated carcinogens, and thus act as important biomarkers for
      chemoprevention. In this study, we tested the chemopreventive activity of
      taxifolin, a flavanon compound purified from a mongolian medicinal plant, by
      measuring quinone reductase (QR) activity in HCT 116 cells. Taxifolin induced
      significant QR activity, but displayed relatively low cytotoxicity in cells
      (chemoprevention index=5.75). To identify the target genes regulated by
      taxifolin, DNA microarray was performed with a 3K human cancer chip containing
      3096 human genes associated with carcinogenesis. Significant analysis of
      microarray (SAM) revealed 428 differentially expressed (DE) genes as
      statistically significant, with a false discovery rate (FDR) of 57.2%
      (delta=0.3366). Sixty-five genes, including a few detoxification enzymes (NQO1,
      GSTM1) and an antioxidant enzyme (TXNRD1), were up-regulated and 363 genes were
      down-regulated in the presence of 60 microM taxifolin. In view of the finding
      that selected genes of interest contained antioxidant response element (ARE), we
      hypothesize that taxifolin modulates chemopreventive genes through activation of
      the ARE. Transient transfection experiments using the ARE QR-CAT construct
      demonstrate that taxifolin significantly activates ARE, but not xenobiotic
      response element (XRE). In conclusion, taxifolin acts as a potential
      chemopreventive agent by regulating genes via an ARE-dependent mechanism.

PMID- 17541157
TI  - WRN functions in a RAD18-dependent damage avoidance pathway.
AB  - Werner syndrome (WS), caused by mutations in a gene (WRN) that encodes a RecQ DNA
      helicase, is characterized by premature aging and cancer predisposition. Cells
      derived from WS patients show sensitivity to several DNA damaging agents.
      Previous studies revealed that the WRN protein plays roles in DNA repair or
      damage tolerance, although it was not yet assigned to a specific pathway. Here we
      examined the relationship between WRN and the post-replication repair protein
      RAD18 by generating deletion derivatives in chicken DT40 cells. The frequency of
      spontaneous sister chromatid exchange in WRN(-/-)/RAD18(-/-) double mutant cells
      was slightly increased compared to that of either single mutant. However, the
      sensitivity of WRN(-/-)/RAD18(-/-) cells to 4-nitroquinoline 1-oxide and methyl
      methanesulfonate was almost the same as that of RAD18(-/-) cells. Moreover, the
      cisplatin sensitivity of RAD18(-/-) cells was slightly suppressed by disruption
      of WRN. These data suggest that WRN functions in a pathway involving RAD18 under
      damage-inducing conditions.

PMID- 17541158
TI  - B-type natriuretic peptide enhances mild hypoxia-induced apoptotic cell death in
      cardiomyocytes.
AB  - In the case of left ventricle remodeling after myocardial infarction,
      cardiomyocyte apoptosis is attributed to increased cardiac workload by the
      stimulus such as chronic hypoxia. B-Type natriuretic peptide, being known as a
      reliable prognostic of cardiovascular pathology, plays an important role in the
      myocardial infarction. However, the action of B-type natriuretic peptide on
      cardiomyocytes undergoing apoptosis is unclear. In the present study, B-type
      natriuretic peptide have exhibited the enhancive effects on the mild hypoxia
      induced cardiomyocyte apoptosis with the manifestation of facilitating
      phosphatidylserine evagination and increasing typical fragmented nuclei. In
      addition, B-type natriuretic peptide aggravated the dissipation of delta psi(m),
      the depletion of intracellular ATP and the increase of caspase-3 activity. 8
      Bromo-cGMP, which increased cGMP independent of B-type natriuretic peptide, could
      mimic B-type natriuretic peptide's effects; whereas cGMP-dependent protein kinase
      inhibitor, Rp-8-br-cGMP inhibited that. Further study revealed the enhancive
      effect of BNP on down-regulation of Bcl-2 mRNA expression in the presence of mild
      hypoxia. In conclusion, the present study demonstrated that B-type natriuretic
      peptide aggravated the cardiomyocyte apoptosis by influencing hypoxia-induced
      mitochondrial death pathway, which is true at least in this oxygen deprivation
      model; and this effect was partially realized through intracellular cGMP.

PMID- 17541159
TI  - Effects of epigallocatechin gallate on diethyldithiocarbamate-induced pancreatic
      fibrosis in rats.
AB  - Epigallocatechin gallate (EGCG), a major component of green tea extracts, is
      known to have anti-fibrotic properties in many organs. The aim of present study
      was to investigate effects of EGCG on rat pancreatic fibrosis induced by
      diethyldithiocarbamate (DDC). Oral gavages of different dose of EGCG (50, 100 and
      200 mg/kg daily for 8 weeks) ameliorated histological changes and significantly
      suppressed collagen deposition in a dose-dependent manner. Meanwhile,
      administration of EGCG inhibited overexpression of TGF-beta1 and alpha-smooth
      muscle actin (a symbol of activation of pancreatic stellate cells). Moreover,
      EGCG has a potent influence on expression of Smads (downstream transcription
      factor of TGF-beta1). EGCG suppressed the expression of Smad3 and enhanced the
      expression of Smad7. In conclusion, our results demonstrated that EGCG attenuated
      rat pancreatic fibrosis induced by DDC and therefore may be an anti-fibrogenic
      candidate in the pancreatic fibrosis.

PMID- 17541160
TI  - 4-Hydroxykobusin inhibits the induction of nitric oxide synthase by inhibiting NF
      kappaB and AP-1 activation.
AB  - We recently isolated a novel lignan, 4-hydroxykobusin from Geranium thunbergii
      (Liu et al., Arch. Pharm. Res., 29, 1109-1113, 2006). Here, we studied its effect
      on the expression of inducible nitric oxide synthase (iNOS) gene in RAW264.7
      cells. 4-Hydroxykobusin inhibited nitric oxide (NO) production in a concentration
      dependent manner and blocked the lipopolysaccharide (LPS)-induced expression of
      inducible nitric oxide synthase (iNOS). To identify the mechanistic basis for its
      inhibition of iNOS induction, we examined the effect of 4-hydroxykobusin on the
      transactivation of iNOS gene by luciferase reporter activity using -1.59 kb
      flanking region. The lignan suppressed the reporter gene activity and the LPS
      induced reporter activations of nuclear factor-kappaB (NF-kappaB) and activator
      protein-1 (AP-1) were also significantly blocked by 4-hydroxykobusin. These
      findings suggest that the inhibition of LPS-induced NO formation by 4
      hydroxykobusin is due to its inhibition of NF-kappaB and AP-1 activation.

PMID- 17541161
TI  - The role of nitric oxide in radiation damage.
AB  - This study investigated the role of nitric oxide in radiation-induced damage by
      examining changes in mouse serum nitrate concentrations after irradiation. In
      addition, the contribution of S-2-aminoethylisothiourea 2HBr (AET) to the
      mechanisms of radiation damage protection was also clarified. The serum nitrate
      concentration increased as soon as 1.5 h after irradiation, and after 2.5 to 3.0
      h the concentrations were significantly higher compared with normal levels.
      Normal levels were re-established after 12 h. Post-irradiation serum nitrate
      concentrations increased dose-dependently with irradiation dose (19.6-31.5 Gy).
      AET suppressed increases in the serum nitrate concentration following irradiation
      while 2-mercaptoethylamine HCl (MEA) did not. AET has an inhibitory effect on
      inducible nitric oxide synthase (iNOS); therefore, the increase in nitric oxide
      after irradiation may be produced by iNOS. Combined administration of irradiation
      and lipopolysaccharide (LPS) induced a significant increase in serum nitrate
      concentration, and a significant decrease in survival rate, compared with
      irradiation alone. The administration of AET or aminoguanidine increased survival
      rate following irradiation. In contrast to findings after LPS administration, IL
      1beta and IFN-gamma were not determined in serum following irradiation. Existing
      iNOS is activated by irradiation, and nitric oxide production appears to increase
      without iNOS induction. Thus, the irradiation-induced increase in nitric oxide
      may be related to lethal injury.

PMID- 17541162
TI  - Schisandrin B decreases the sensitivity of mitochondria to calcium ion-induced
      permeability transition and protects against carbon tetrachloride toxicity in
      mouse livers.
AB  - Schisandrin B (Sch B), a dibenzocyclooctadiene derivative isolated from the fruit
      of Schisandra chinensis, has been shown to protect against carbon tetrachloride
      (CCl4) hepatotoxicity in mice. In order to elucidate the molecular mechanism
      underlying the hepatoprotection afforded by Sch B, the effect of Sch B treatment
      on the sensitivity of mitochondria to Ca2+-stimulated permeability transition
      (PT) was investigated in mouse livers under normal and CCl4-intoxicated
      conditions. CCl4 hepatotoxicity caused an increase in the sensitivity of
      mitochondria to Ca2+-stimulated PT in vitro. The enhanced sensitivity to
      mitochondrial PT was associated with increases in mitochondrial Ca2+ content as
      well as the extent of reactive oxidant species (ROS) production and cytochrome c
      release. The hepatoprotection afforded by Sch B pretreatment against CCl4
      toxicity was paralleled by the decrease in the sensitivity of hepatic
      mitochondria to Ca2+-stimulated PT as well as the attenuations of mitochondrial
      Ca2+ loading, ROS production and cytochrome c release under CCl4-intoxicated
      condition. In conclusion, the results suggest that the hepatoprotection afforded
      by Sch B pretreatment against CCl4 toxicity may be related to the increase in the
      resistance of hepatic mitochondria to Ca2+-stimulated PT.

PMID- 17541163
TI  - Apoptosis-inducing activity of new pyrazole emodin derivatives in human
      hepatocellular carcinoma HepG2 cells.
AB  - A series of new pyrazole derivatives from emodin synthesized in our lab have been
      shown to have much stronger cytotoxicity than emodin against various tumor cell
      lines. This study was to examine the apoptosis-inducing activity of these new
      emodin derivatives in human hepatocellular carcinoma HepG2 cell culture for a
      better understanding of their cytotoxic effects on the cancer cells. Several
      major events in the induction of cell apoptosis, nuclear chromatin condensation,
      DNA fragmentation, caspase-3 activation and poly ADP-ribose polymerase (PARP)
      cleavage were detected in the cells after treatment with the compounds at various
      concentrations. Of the seven emodin derivatives tested at a dose of 10 microM and
      within a treatment period of 24 h, only compounds 1 and 3 effectively induced all
      these apoptotic events in the cancer cells. The apoptosis-inducing activity of
      the compounds showed a positive correlation to their cytotoxic activity,
      suggesting a close connection between the growth inhibition and apoptosis
      induction of the cancer cells by these pyrazole emodin derivatives.

PMID- 17541164
TI  - Anchoring cationic amphiphiles for nucleotide delivery: significance of DNA
      release from cationic liposomes for transfection.
AB  - We have designed and synthesized lithocholic acid-based cationic amphiphile
      molecules as components of cationic liposomes for gene transfection
      (lipofection). To study the relationship between the molecular structures of
      those amphiphilic molecules, particularly the extended hydrophobic appendant
      (anchor) at the 3-hydroxyl group, and transfection efficiency, we synthesized
      several lithocholic and isolithocholic acid derivatives, and examined their
      transfection efficiency. We also compared the physico-chemical properties of
      cationic liposomes prepared from these derivatives. We found that isolithocholic
      acid derivatives exhibit higher transfection efficiency than the corresponding
      lithocholic acid derivatives. This result indicates that the orientation and
      extension of hydrophobic regions influence the gene transfection process.
      Isolithocholic acid derivatives showed a high ability to encapsulate DNA in a
      compact liposome-DNA complex and to protect it from enzymatic degradation.
      Isolithocholic acid derivatives also facilitated the release of DNA from the
      liposome-DNA complex, which is a crucial step for DNA entry into the nucleus. Our
      results show that the transfection efficiency is directly influenced by the
      ability of the liposome complex to release DNA, rather than by the DNA
      encapsulating ability. Molecular modeling revealed that isolithocholic acid
      derivatives take relatively extended conformations, while the lithocholic acid
      derivatives take folded structures. Thus, the efficiency of release of DNA from
      cationic liposomes in the cytoplasm, which contributes to high transfection
      efficiency, appears to be dependent upon the molecular shape of the cationic
      amphiphiles.

PMID- 17541165
TI  - Antihyperglycemic effect of Cephalotaxus sinensis leaves and GLUT-4 translocation
      facilitating activity of its flavonoid constituents.
AB  - The objectives of this study were to investigate the antihyperglycemic effect of
      Cephalotaxus sinensis leaves and to identify the active components. The
      antihyperglycemic effect of various fractions (FA, FB, FC, FD) of the 80% ethanol
      extract of the leaves was evaluated in streptozotocin (STZ)-induced diabetic
      rats. Among the tested fractions, FC was the most active. FC (0.48 g/kg) given
      orally for 10 d reduced significantly (p<0.001) the blood glucose of STZ-induced
      diabetic rats. The food and water intakes of FC (0.48 g/kg)-treated diabetic rats
      were reduced significantly (p<0.001) when compared to the 0.5% carboxymethyl
      cellulose (CMC)-treated diabetic rats. The activity-guided fractionation of the
      ethanol extract of C. sinensis leaves furnished three flavonoid compounds,
      apigenin-5-O-[alpha-L-rhamnopyranosyl-(1-->4)-6-O-beta-D-acetylglucopyranoside]
      (1), apigenin (2), and apigenin-5-O-[alpha-L-rhamnopyranosyl-(1-->4)-6-O-beta-D
      glucopyranoside] (3). The elevation of GLUT-4 protein level in membrane
      preparations from mice adipocytes was detected by Western blot analysis after
      adipocytes were pre-incubated with FC (0.1, 1, 10 mg/ml), apigenin (0.1, 2 mg/ml)
      and apigenin-5-O-[alpha-L-rhamnopyranosyl-(1-->4)-6-O-beta-D
      acetylglucopyranoside] (0.1, 2 mg/ml), respectively. Phytochemical investigation
      and HPLC-DAD analysis of FC indicated that the flavonoids were the major
      constituents in this fraction. These results suggest that the fraction from C.
      sinensis leaves is a promising drug for the treatment of diabetes, and that the
      flavonoids from this plant are the active constituents.

PMID- 17541166
TI  - Resveratrol oligomers from Vitis amurensis attenuate beta-amyloid-induced
      oxidative stress in PC12 cells.
AB  - Oxidative damage induced by beta-amyloid (Abeta) is closely associated with the
      hallmark pathologies of Alzheimer's disease (AD) and may play a critical role in
      the development of AD. In this study, the protective effects of vitisin A and
      heyneanol A, resveratrol oligomers isolated from Vitis amurensis Rupr.
      (Vitaceae), against Abeta-induced oxidative cell death were investigated using
      rat pheochromocytoma (PC12) cells. Exposure of PC12 cells to the Abeta (20
      microM) for 24 h resulted in neuronal cell death, whereas pretreatment with
      vitisin A or heyneanol A at the concentration range of 5-50 microM reduced Abeta
      induced cell death. In addition, Abeta-induced elevation of reactive oxygen
      species generation, the primary cause of Abeta-induced oxidative stress, was
      attenuated by treatment of vitisin A or heyneanol A (10, 25, 50 microM). Abeta
      treated cells also displayed characteristic features of apoptosis such as
      induction of DNA fragmentation and caspase-3 activation, but vitisin A and
      heyneanol A (10, 50 microM) significantly suppressed these events. These results
      suggest that vitisin A and heyneanol A prevent Abeta-induced neurotoxicity
      through attenuating oxidative stress induced by Abeta, and may be useful as
      potential preventive or therapeutic agents for AD.

PMID- 17541167
TI  - Inhibitory effect of p-hydroxybenzyl alcohol on tyrosinase activity and
      melanogenesis.
AB  - Tyrosinase is a key enzyme catalyzing the rate-limiting step for the biosynthesis
      pathway of melanin pigment, which is the most important determinant of the color
      of skin. Inhibiting tyrosinase and repressing melanocyte metabolism can reduce
      melanin production. Among the possible melanin reducing compounds, tyrosinase
      inhibitors are most promising for treating pigmentation and are used as skin
      whitening agents in the cosmetic industry. In our investigation, some new
      tyrosinase inhibitors from plants have been identified to have high tyrosinase
      inhibitory activity. Specifically, p-hydroxybenzyl alcohol (4HBA) was found to
      inhibit the monophenolase activity of mushroom tyrosinase. When 4HBA binds with
      the enzyme, conformation of the enzyme is altered and its activity decreases. The
      inhibitory effect of 4HBA on melanogenesis has been studied using cultured mouse
      melanoma cells. Melanin synthesis in cell culture with 4HBA at 1.0 mM was
      decreased to 45% of control and below 1.0 mM there was no effect on cell growth.
      The inhibitory effects of 4HBA on melanogenesis are due to the direct inhibition
      of melanosomal tyrosinase activity, rather than to the suppression of tyrosinase
      gene. These results showed that 4HBA is a promising and safe agent for skin
      whitening.

PMID- 17541168
TI  - Dihydrotestosterone inhibits tumor necrosis factor alpha induced interleukin
      1alpha mRNA expression in rheumatoid fibroblast-like synovial cells.
AB  - Rheumatoid arthritis (RA) is a chronic inflammatory disease that affects multiple
      synovial joints. Proinflammatory cytokines, such as interleukin-1 (IL-1) and
      tumor necrosis factor (TNF)alpha play important roles as principle inflammatory
      and destructive components of the disease. RA is known to be associated with
      significant gender differences in its prevalence and clinical features. We found
      that a potent androgen, 5alpha-dihydrotestosterone (DHT) inhibits IL-1alpha mRNA
      expression induced by TNFalpha and the DHT effect was inhibited by an androgen
      receptor antagonist, hydroxyflutamide (OHF). DHT inhibited the NF-kappaB
      activation induced by TNFalpha in a manner dependent on the androgen receptor
      (AR). These results suggest that DHT inhibits the TNFalpha-induced IL-1alpha mRNA
      expression by inhibiting NF-kappaB activation, and contributes to the gender
      differences of the disease.

PMID- 17541169
TI  - Correlation of induction of ATP binding cassette transporter A5 (ABCA5) and ABCB1
      mRNAs with differentiation state of human colon tumor.
AB  - The ATP binding cassette transporter subtype A5 (ABCA5)-like transporters ABCA5,
      ABCA6, ABCA8, ABCA9 and ABCA10 form a unique gene cluster within the ABC
      transporter superfamily, though their function is still poorly understood. The
      purpose of this study is to examine whether ABCA5-like transporters may play a
      role in tumor development by measuring their mRNA levels in human tissues and
      tumors. Intense mRNA expression of human ABCA5-like transporters was detected in
      the brain. ABCA5 and ABCA8 mRNAs were detected in spleen, testis and ovary. ABCA5
      mRNA was also detected in liver and pancreas. ABCA6 mRNA was detected in lung and
      liver, and ABCA8 was detected in lung. ABCA6, ABCA7 and ABCA8 mRNAs were not
      detected in any tumors, but weak mRNA expression of ABCA10 was detected in all
      tumors examined. ABCA5 mRNA was detected in poorly differentiated colon
      adenocarcinoma (GI-112) and undifferentiated ovarian carcinoma (GI-102), but not
      in normal colon. ABCB1 mRNA was also detected in GI-112, while ABCC1 and ABCA2
      mRNAs were not. In contrast, ABCC1 and ABCA2 mRNAs, but not ABCA5 or ABCB1 mRNA,
      were detected in well differentiated colon adenocarcinoma (CX-1). Thus, induction
      of ABCA5, together with ABCB1, appears to be correlated with the differentiation
      state of human colon tumors, and may have a role in tumor development.

PMID- 17541170
TI  - Antimicrobial activity of oleanolic acid from Salvia officinalis and related
      compounds on vancomycin-resistant enterococci (VRE).
AB  - An extract from Salvia officinalis (Sage) leaves showed antimicrobial activity
      against vancomycin-resistant enterococci (VRE). We isolated the effective
      compound and identified it as oleanolic acid, a triterpenoid. We also tested
      antimicrobial activity of similar triterpenoids, ursolic acid, uvaol, betulinic
      acid and betulin. We found that ursolic acid also showed antimicrobial activity
      against VRE. The minimum inhibitory concentrations (MICs) of oleanolic acid and
      ursolic acid were 8 and 4 microg/ml, respectively. These two compounds also
      showed antimicrobial activity against Streptococcus pneumoniae and methicillin
      resistant Staphylococcus aureus (MRSA). These compounds showed bactericidal
      activity against VRE at least for 48 h when added at concentrations that were two
      times higher than their MICs.

PMID- 17541171
TI  - Platelet-activating factor (PAF) receptor binding antagonist activity of the
      methanol extracts and isolated flavonoids from Chromolaena odorata (L.) King and
      Robinson.
AB  - The leaf, stem and root extracts of Chromolaena odorata were evaluated for their
      effect on platelet-activating factor (PAF) receptor binding on rabbit platelets
      using 3H-PAF as a ligand. The leaf extract demonstrated high PAF receptor binding
      inhibitory activity of 79.2+/-2.1% at 18.2 microg/ml. A total of eleven
      flavonoids were subsequently isolated from the active leaf extract and evaluated
      for their effects on PAF receptor binding. Eight of the flavonoids exhibited >50%
      inhibition on the binding activity at 18.2 microg/ml. These flavonoids were
      identified as eriodictyol 7,4'-dimethyl ether, quercetin 7,4'-methyl ether,
      naringenin 4'-methyl ether, kaempferol 4'-methyl ether, kaempferol 3-O
      rutinoside, taxifolin 4'-methyl ether, taxifolin 7-methyl ether and quercetin 4'
      methyl ether. Their IC50 values ranged from 19.5 to 62.1 microM.

PMID- 17541172
TI  - Inhibitory effect of schizandrin on passive cutaneous anaphylaxis reaction and
      scratching behaviors in mice.
AB  - To evaluate the antiallergic effect of the fruit of Schizandra chinensis Baill
      (Family Magnoliaceae), which inhibited the mouse passive cutaneous anaphylaxis
      (PCA) reaction in a preliminary experiment, its main constituent, schizandrin,
      was isolated and its antiallergic effect investigated. Schizandrin inhibited the
      PCA reaction induced by the IgE-antigen complex, the scratching behaviors induced
      by compound 48/80 and the serum IgE production induced by ovalbumin. Schizandrin
      also inhibited the in vitro degranulation of compound 48/80-induced rat
      peritoneal mast cells and IgE-induced RBL 2H3 cells. Schizandrin reduced the
      protein expressions of TNF-alpha and IL-4 in IgE-induced RBL 2H3 cells. These
      findings suggest that schizandrin can improve IgE-induced anaphylaxis and
      scratching behaviors.

PMID- 17541173
TI  - Magnoflorine from Coptidis Rhizoma protects high density lipoprotein during
      oxidant stress.
AB  - The objective of the present study was to investigate the beneficial properties
      of magnoflorine, an alkaloid isolated from coptidis rhizoma, on protecting human
      high density lipoprotein (HDL) against lipid peroxidation. Magnoflorine exerts an
      inhibitory effect against Cu2+-induced lipid peroxidation of HDL, as showed by
      prolongation of lag time from 62 to 123 min at the concentration of 3.0 microM.
      It also inhibits the generation of thiobarbituric acid reactive substances
      (TBARS) in the dose-dependent manners with IC50 values of 2.3+/-0.2 microM and
      6.2+/-0.5 microM since HDL oxidation mediated by either catalytic Cu2+ or thermo
      labile radical initiator (AAPH), respectively. Separately, Cu2+ oxidized HDL lost
      the antioxidant action but the inclusion of magnoflorine/Cu2+ oxidized HDL can
      protect LDL oxidation according to increasing magnoflorine concentration. The
      results suggest that magnoflorine may have a role to play in preventing the HDL
      oxidation.

PMID- 17541174
TI  - Cloning and expression of calmodulin gene in Scoparia dulcis.
AB  - A homology-based cloning strategy yielded a cDNA clone, designated Sd-cam,
      encoding calmodulin protein from Scoparia dulcis. The restriction digests of
      genomic DNA of S. dulcis showed a single hybridized signal when probed with the
      fragment of this gene in Southern blot analyses, suggesting that Sd-cam occurs as
      a sole gene encoding calmodulin in the plant. The reverse-transcription
      polymerase chain reaction analysis revealed that Sd-cam was appreciably expressed
      in leaf, root and stem tissues. It appeared that transcription of this gene
      increased transiently when the leaf cultures of S. dulcis were treated with
      methyl jasmonate and calcium ionophore A23187. These results suggest that
      transcriptional activation of Sd-cam is one of the early cellular events of the
      methyl jasmonate-induced responses of S. dulcis.

PMID- 17541175
TI  - Vasorelaxant effects of Acer nikoense extract and isolated coumarinolignans on
      rat aortic rings.
AB  - The organic extract of the heartwood of Acer nikoense Maxim. (Aceraceae) showed
      vasorelaxant activity on rat aorta with or without endothelium. Coumarin
      [scopoletin (1)] and coumarinolignans [cleomiscosin A (2) and aquillochin (3)]
      were isolated as major constituents from the organic extract of the heartwood of
      A. nikoense. Compounds 1-3 exhibited moderate vasorelaxant effects on rat aorta,
      while 2 and 3 showed vasorelaxant effects in the norepinephrine-stimulated and
      also in high K+-depolarized preparations.

PMID- 17541176
TI  - Relationship between amount of drug delivered to lungs and amount released from
      Diskhaler by inhalation with tapping.
AB  - It is well known that drug residue remains in a fluticasone propionate Diskhaler
      (FP-DH) following a single inhalation. Thus, the inspiratory ability of the
      patient has an influence on the effects of the drug. In a previous study, we
      reported that the amount of drug remaining in an FP-DH was decreased by tapping
      the device after the first inhalation. In the present study, we investigated the
      relationship between the amount of drug delivered to the lungs and amount of drug
      released from the FP-DH by inhalation along with tapping using an in vitro model.
      We measured the amounts delivered to the throat, stage 1, and stage 2 of a twin
      impinger device by HPLC-UV, following inhalation and tapping of 100 microg of FP
      DH at various inspiratory flow rates, which ranged from 11.5 to 73.6 l/min for 2
      s. A positive linear correlation between the amount of drug released from the FP
      DH and that deposited in stage 2 was observed. Amounts deposited in stage 2
      following tapping were estimated to be 6.0 microg at an inspiratory flow rate of
      20 l/min and 10.6 microg at 60 l/min, while those without tapping were 2.0 microg
      and 10.2 microg, respectively. Notably, at an inspiratory flow rate of 20 l/min,
      the amount of drug deposited in stage 2 by tapping was increased about 3-fold in
      comparison to that without tapping. Our results indicate that the amount of drug
      deposited in stage 2, i.e., the lung in our model, is increased by tapping of the
      device, which would be particularly helpful for patients with a lower level of
      inspiratory ability.

PMID- 17541177
TI  - Preparation, characterization and evaluation of coenzyme Q10 binary solid
      dispersions for enhanced solubility and dissolution.
AB  - Phase solubility behavior of coenzyme Q10 (CoQ10) at 25 degrees C in various
      molar solutions of poloxamer 188 (P188) in water was observed and their binary
      solid dispersions (BSD) at different weight ratios were prepared by a simple,
      rapid, cost effective, uncomplicated and potentially scalable low temperature
      melting method. BSDs were characterized by scanning electron microscopy (SEM) and
      differential scanning calorimetry (DSC), and evaluated for improved solubility at
      25 degrees C and 37 degrees C and in-vitro release of CoQ10 at 37 degrees C in
      distilled water. Solubility of CoQ10 increased with increasing concentrations of
      P188 in water. Gibbs free energy (deltaG(o)tr) values were all negative
      indicating the spontaneous nature of CoQ10 solubilization and decreased with
      increasing concentration of P188 demonstrating that the reaction conditions
      became more favorable as the concentration of P188 increased. DSC and SEM
      analysis indicated that the homogeneity of dispersion was not at the molecular
      level. However, BSDs exhibited a remarkably improved aqueous solubility and
      dissolution of CoQ10.

PMID- 17541178
TI  - Comparative study of circadian variation in numbers of peripheral blood cells
      among mouse strains: unique feature of C3H/HeN mice.
AB  - We examined strain differences in numbers of blood cells and their circadian
      rhythms in male Jcl:ICR, BALB/cA, C57BL/6J and C3H/HeN mice. The total numbers of
      circulating white blood cells (WBCs) were increased during subjective day and
      night, and the peaks in the active period were common to all strains. However,
      the number of WBCs in C3H/HeN mice remained lower and plasma levels of
      corticosterone (CS) were slightly higher throughout the day compared with the
      other strains. The numbers of circulating red blood cells (RBC) also differed
      according to strain. The numbers of RBCs, hematocrit (HCT) and hemoglobin (HGB)
      were considerably lower in C3H/HeN mice compared with the other strains, although
      mean corpuscular hemoglobin (MCH) and mean corpuscular volume (MCV) were highest
      among the tested strains. We found that serum erythropoietin (EPO) levels were
      considerably higher in C3H/HeN mice than in the other three strains. The high EPO
      level might be related to the unique features of RBCs in C3H/HeN mice. The
      present observations provide basic information about the numbers of peripheral
      blood cells and their circadian rhythm in mouse models and also demonstrate a
      unique feature of C3H/HeN mice.

PMID- 17541179
TI  - Absolute quantification of four isoforms of the class I phosphoinositide-3-kinase
      catalytic subunit by real-time RT-PCR.
AB  - Class I phosphoinositide-3-kinase (PI3K) consists of four isoforms of the
      catalytic subunit, p110alpha, -beta, -delta and -gamma, generated from the genes
      PIK3CA, -B, -D and -G, respectively. These isoforms show different tissue
      distribution and some specific and indispensable functions in various biological
      pathways such as development, inflammation, autoimmunity and malignancy. In human
      cancers, frequent genomic amplification and gain-of-function mutations of PIK3CA
      were reported, which suggests an oncogenic potential. However, the role played by
      the other three isoforms in human cancer remains to be determined. We wanted to
      investigate the relationship between all the isoforms in human cancers. Here, we
      have established a system for the simultaneous absolute-quantification of all
      four isoforms by real-time reverse transcription polymerase chain reaction (RT
      PCR). The reliability of this system was confirmed using three main criteria: (i)
      good correlation of each standard curve, (ii) high specificity of the PCR
      reactions and (iii) excellent reproducibility. Using this system, we investigated
      human monocytic leukemia cells (U937) to analyze expression of all four isoforms.
      The biological implications of the expression level of the four isoforms of class
      I PI3K catalytic subunit are discussed.

PMID- 17541180
TI  - Study on the cell wall skeleton derived from Mycobacterium bovis BCG Tokyo 172
      (SMP-105): establishment of preparation and analytical methods.
AB  - Mycobacterial cell walls have diverse adjuvant activities, and in particular,
      cell wall skeleton (CWS) of Mycobacterium bovis BCG has been expected as a drug
      for tumor immunotherapy. However, its molecular structure-biological activity
      relationship has not been fully elucidated despite more than 30 years of
      intensive research. Since it is important to secure purified CWS for such
      investigation, we established a preparation method of CWS from M. bovis BCG Tokyo
      172 (SMP-105) and developed accurate, precise, and reliable analytical methods,
      based on previous reports. Furthermore, we confirmed that SMP-105 is composed of
      mycolic acids; arabinogalactan consisting of arabinose, galactose, and rhamnose;
      and peptidoglycan consisting of alanine, glutamic acid, diaminopimeric acid,
      muramic acid, glucosamine, and galactosamine. We also determined the levels of
      potential impurities that might be contaminated in the original bacterium or
      arise during the manufacturing process, such as glucose, mannose, non-constituted
      amino acids, as well as nucleic acid, trehaolse di-mycolate, and bacterial
      endotoxins. These results demonstrated that the prepared SMP-105 was of
      sufficient quality for research into the chemistry, bioactivity, and structure
      activity relationship of CWS.

PMID- 17541181
TI  - Structures and DNA-binding and cleavage properties of ternary copper(II)
      complexes of glycine with phenanthroline, bipyridine, and bipyridylamine.
AB  - The crystal structures of the series of three complexes, [Cu(Gly)(bpy)Cl].2H2O
      (1) (Gly=glycine; bpy=2,2'-bipyridine), [Cu(Gly)(phen)Cl]2.7H2O (2) (phen=1,10
      phenanthroline), and [Cu(Gly)(bpa)(H2O)Cl] (3) (bpa=2,2'-bipyridylamine) were
      determined, and the coordination modes of Cu(II) ternary complexes were compared.
      The central Cu(II) atoms of complexes 1 and 3 have a similar distorted octahedral
      coordination geometry, while the Cu(II) atom of complex 2 has a distorted square
      pyramidal coordination. In all complexes, the aromatic heterocyclic compounds
      bpy, phen, and bpa, behave as a bidentate N,N' ligand, and Gly behaves as a
      bidentate N,O ligand. DNA-binding properties of the complexes to calf thymus (CT)
      DNA were studied by using the fluorescence method. Each of the complexes showed
      binding propensity to CT DNA with the relative order 2>3> or =1. DNA cleavage
      studies indicate that each of the complexes, especially 2, can cleave plasmid
      supercoiled pBR322 DNA in the presence of H2O2 and ascorbic acid with cleavage
      efficiency in the order 2>3 approximately 1. The degradation of the conformation
      of CT DNA by the complexes was also reflected in the decrease in the intensities
      of the characteristic CD bands with the relative order 2>3 approximately 1.

PMID- 17541182
TI  - Deprotection of a silyl group with mesoporous silica.
AB  - The triethylsilyl (TES) group of silyl ethers of several types is selectively and
      easily removed in the presence of a t-butyldimethylsilyl (TBDMS) group with a
      mesoporous silica MCM-41/MeOH heterogeneous system. Comparison of the efficiency
      was carried out among several solvents, and among such promoters as common
      zeolites and ion-exchange resins. Furthermore, FSM-16, another mesoporous silica,
      was examined for the possibility of recycling by re-calcination at 400 degrees C
      after the reaction.

PMID- 17541183
TI  - Simultaneous spectrophotometric determination of levodopa and carbidopa in
      pharmaceutical formulations and water samples by using mean centering of ratio
      spectra and H-point standard addition methods.
AB  - Two spectrophotometric methods are described for the simultaneous determination
      of binary mixtures of carbidopa and levodopa in pharmaceutical formulations,
      without prior separation steps, using the mean centering of ratio spectra and H
      point standard addition methods (HPSAM). The methods are based on the difference
      in the absorption spectra for the products of the reaction of carbidopa and
      levodopa with 4-aminobenzoic acid in the presence of periodate ion at pH 4.0. The
      methods allow rapid and accurate determination of carbidopa and levodopa. The
      results showed that the methods were capable to simultaneous determination of
      0.30-10.00 microg ml(-1) and 0.50-10.00 microg ml(-1) each of carbidopa and
      levodopa. The proposed methods were successfully applied to the simultaneous
      determination of carbidopa and levodopa in pharmaceutical samples.

PMID- 17541184
TI  - Studies on the interaction of cinnamic acid with bovine serum albumin.
AB  - The interaction between cinnamic acid and bovine serum albumin (BSA) have been
      studied at three temperatures, 296, 303 and 310 K. Fluorescence quenching spectra
      in combination with Fourier transform infrared (FT-IR) spectroscopy and circular
      dichroism (CD) spectroscopy was used to investigate the drug-binding mode, the
      binding constant and the protein structure changes in the presence of cinnamic
      acid in aqueous solution at pH 7.40. The fluorescence quenching constant K(q),
      K(sv) and the binding constant K were calculated according to Stern-Volmer
      equation based on the quenching of the fluorescence of BSA in the presence of
      cinnamic acid. The thermodynamic parameters, the enthalpy (DeltaH) and the
      entropy change (DeltaS) were estimated to be -16.457 kJ mol(-1) and 38.028 J mol(
      1) K(-1) according to the van't Hoff equation. The displacement experiment shows
      that cinnamic acid can bind to the subdomain IIA (corresponding to Sudlow's drug
      binding site I). The distance between the tryptophan residues in BSA and cinnamic
      acid bound to site I was estimated to be 1.63 nm using Foster's equation on the
      basis of fluorescence energy transfer. The decreased binding constant in the
      presence of common ions indicates that common ions have effect on drug-BSA
      system.

PMID- 17541185
TI  - Neolemnane-type sesquiterpenoids from a formosan soft coral Paralemnalia
      thyrsoides.
AB  - Six new sesquiterpenoids, paralemnolins D-I (1-6), have been isolated from the
      EtOAc extract of the soft coral Paralemnalia thyrsoides. The structures of these
      metabolites were determined by extensive spectroscopic analysis and by comparison
      of their spectral data with those of related metabolites. The absolute
      stereochemistry of these metabolites was established by application of the
      Mosher's method on 1 and on the basis of the absolute structures of other related
      compounds previously isolated from the soft corals of the genera Paralemnalia and
      Lemnalia. Cytotoxicity of these metabolites toward a limited panel of cancer cell
      lines also is reported.

PMID- 17541186
TI  - Discovery of novel 2-anilinopyrazolo[1,5-a]pyrimidine derivatives as c-Src kinase
      inhibitors for the treatment of acute ischemic stroke.
AB  - We synthesized a series of novel 2-anilinopyrazolo[1,5-a]pyrimidine derivatives
      and evaluated their ability to inhibit c-Src kinase; 7-(2-amino-2
      methylpropylamino)-5-cyclopropyl-2-(3,5-dimethoxyphenylamino)pyrazolo[1,5
      a]pyrimidine-3-carboxamide 7o and 7-(2-amino-2-methylpropylamino)-2-(3,5
      dimethoxyphenylamino)-5-methylpyrazolo[1,5-a]pyrimidine-3-carboxamide 7f showed
      potent inhibitory activity. Compound 7f inhibited c-Src selectively and exhibited
      satisfactory central nervous system (CNS) penetration. Furthermore, 7f.HCl
      reduced the infarct volume in vivo in a rat middle cerebral artery (MCA)
      occlusion model when administrated intraperitoneally.

PMID- 17541187
TI  - Prenylbicyclogermacrane diterpenoids from the formosan soft coral Nephthea
      elongata.
AB  - Seven new prenylbicyclogermacrane diterpenoids, pacificins K--Q (1--7), were
      isolated from the methylene chloride solubles of the Formosan soft coral Nephthea
      elongata. Their structures were elucidated by extensive spectroscopic analysis
      and their cytotoxicity against selected cancer cells was measured in vitro.

PMID- 17541188
TI  - Synthesis and antibacterial activity of new N-[2-(thiophen-3-yl)ethyl]
      piperazinyl quinolones.
AB  - As a part of continuing search for potential antibacterial agents in the
      quinolones field, we have synthesized novel quinolone agents bearing N-[2
      (thiophen-3-yl)ethyl] piperazinyl moiety in the 7-position of the quinolone ring.
      In vitro antibacterial evaluation of the target compounds showed that N-[2
      (thiophen-3-yl)ethyl] group attached to piperazine ring served as promising C-7
      substituent for piperazinyl quinolone antibacterials. Among these derivatives,
      ciprofloxacin analogues, containing N-[2-(thiophen-3-yl)-2-hydroxyiminoethyl] or
      N-[2-(thiophen-3-yl)-2-methoxyiminoethyl] residue provided a high inhibition
      against all the tested Gram-positive organisms including methicillin-resistant
      Staphylococcus aureus comparable or superior with respect to the reference drugs
      norfloxacin and ciprofloxacin.

PMID- 17541189
TI  - Facile discrimination of aldose enantiomers by reversed-phase HPLC.
AB  - One-pot reactions of aldoses with L-cysteine methyl ester and o-tolyl
      isothiocyanate yielded methyl 2-(polyhydroxyalkyl)-3-(o-tolylthiocarbamoyl)
      thiazolidine-4(R)-carboxylates. Direct HPLC analysis of the reaction mixture and
      UV detection at 250 nm discriminated D- and L-enantiomers of aldoses. The
      reaction was applied to the determination of absolute configuration the sugar
      residues of an aroma precursor.

PMID- 17541190
TI  - Three new limonoids from Cipadessa cinerascens.
AB  - Three new limonoids, cipadesins D--F (1--3), together with 8,15-dihydroxy-13E
      labdane, beta-sitosterol and beta-daucosterol, were isolated from the leaves and
      bark of Cipadessa cinerascens. Their structures were elucidated by spectral
      evidence. X-Ray crystallographic analysis confirmed the structure of 1.

PMID- 17541191
TI  - Two new sesquiterpenes from Alisma orientalis.
AB  - Two new sesquiterpenoids named alismorientols A (1) and B (2) were isolated from
      the rhizomes of Alisma orientalis collected in Sichuan province, People's
      Republic of China. Their structures were elucidated based on spectroscopic
      analyses (1D and 2D NMR data including HSQC, HMBC, COSY, and ROESY) and X-ray
      crystallographic analysis. Anti-hepatitis B virus (HBV) bioassay revealed that
      compound 1 showed moderate anti-HBV activity in vitro with IC50 for HBsAg: 1.1
      microM, for HBeAg: 14.7 microM.

PMID- 17541192
TI  - Lanostane-type triterpenoids from Diospyros discolor.
AB  - Four new lanostane-type triterpenes, 24-ethyl-3beta-methoxylanost-9(11)-en-25-ol
      (1), 3beta-methoxy-24-methylenelanost-9(11)-en-25-ol (2), 3beta-methoxy-25-methyl
      24-methylenelanost-9(11)-en-21-ol (3) and 3beta-methoxy-24-methyllanosta-9(11),25
      dien-24-ol (4) together with three known triterpenes, betulinaldehyde, betulinic
      acid methyl ester, and ursaldehyde have been isolated from the methanol extract
      of the twigs of Diospyros discolor. The structures of those new compounds were
      elucidated by spectroscopic methods.

PMID- 17541193
TI  - Steroidal alkaloids from Holarrhena antidysenterica (L.) WALL.
AB  - Chemical investigations on the stem bark of Holarrhena antidysenterica resulted
      in the isolation of a new steroidal alkaloid designated as holadysenterine (1),
      together with three known steroidal alkaloids, conessine (2), isoconessimine (3)
      and kurchessine (4). Their structures were elucidated on the basis of 1D- and 2D
      NMR techniques and high-resolution mass spectrometry.

PMID- 17541194
TI  - One-pot synthesis of highly conjugated benzofuran derivatives based on
      electrochemical oxidation of benzenediols in the presence of dibenzoylmethane.
AB  - Electrochemical oxidation of benzenediols (1--4) has been studied in the presence
      of dibenzoylmethane (5) as a nucleophile using cyclic voltammetry and controlled
      potential coulometry. The results indicate that the electrochemically generated
      quinones participate in Michael addition reaction with 5 via various mechanisms
      to produce new benzofuran derivatives. We derived various products based on
      electrochemical oxidation in the controlled potential condition, at carbon
      electrode without toxic reagents in an undivided cell and ambient condition.

PMID- 17541195
TI  - New C18-diterpenoid alkaloids from Delphinium anthriscifolium var. savatieri.
AB  - Five new C18-diterpenoid alkaloids, anthriscifolcines A (1), B (2), C (3), D (4),
      and E (5), together with a known C19-diterpenoid alkaloid delcorine (6), were
      isolated from the whole herb of Delphinium anthriscifolium var. savatieri. The
      structures of these new alkaloids were established on the basis of spectral data
      (1D- and 2D-NMR, HR-ESI-MS).

PMID- 17541196
TI  - Convenient synthetic method for 3-(3-substituted indol-2-yl)quinoxalin-2-ones as
      VEGF inhibitor.
AB  - It has already been reported that 3-(indol-2-yl)quinoxalin-2-ones have a potent
      inhibitory effect on the growth of tumor cells based on anti-angiogenesis
      activity. We have also carried out a structure-activity relationship (SAR) study
      of 3-(indol-2-yl)quinoxalin-2-ones, which showed a potent inhibitory activity
      toward the vascular endothelial growth factor (VEGF)-induced proliferation of
      human mesangial cells and the VEGF-induced auto-phosphorylation of human
      umbilical vein endothelial cells. Moreover, one of these compounds has a potent
      medicinal effect based on anti-angiogenic action, by oral administration (Chart
      1, 9). However, since the existing synthetic methods for the preparation of 3
      (indol-2-yl)quinoxalin-2-ones consist of multiple steps some of which require
      strict anhydrous conditions, a convenient and simple synthetic method in place of
      the existing method is desirable. As a result of the investigations into the
      synthetic procedures, 3-(3-substituted indol-2-yl)quinoxalin-2-ones can be easily
      prepared by the condensation of 3-substituted indoles with quinoxalin-2-ones in
      the presence of trifluoroacetic acid (TFA). Herein, we report the examination of
      these reaction conditions and the application of this new synthetic method to the
      synthesis of the derivatives as VEGF inhibitors.

PMID- 17541197
TI  - Chemical constituents of Nepalese propolis (II).
AB  - A novel flavanonol (1), three new isoflavones (2-4) and a new flavan-3-ol (5)
      were isolated along with ten other known flavonoids (6-15) from the methanolic
      extract of propolis collected from Chitwan, Nepal. Their structures were
      determined on the basis of spectral analysis.

PMID- 17541198
TI  - Synthesis of bioreductive esters from fungal compounds.
AB  - Four new bioreductive esters (7-10) have been synthesized. Their structures
      composed of trimethyl lock containing quinone propionic acid with an ester
      linkage to the fungal cytotoxic compounds; preussomerin G (1), preussomerin I
      (2), phaseolinone (3) and phomenone (4). The synthesized esters are aimed to act
      via reductive activation specifically at the cancer cells, resulting from hypoxia
      and overexpression of reductases. Hence, the toxicity will be lessened during
      distribution across the normal cells. The anticancer activity was determined in
      cancer cell lines with reported reductase i.e., BC-1 cells and NCI-H187 as well
      as in non-reductase containing cancer cells; KB cells. When considering each cell
      lines, result showed that structure modification giving to 7-10 led to less
      cytotoxicity than their parent compounds (1-4). Both 7 and 8 were strongly
      cytotoxic (IC50 < or = 5 microg/ml) to NCI-H187, whereas 9 and 10 were moderately
      cytotoxic (IC50 = 6-10 microg/ml) to BC-1 cells. Additional study of stability of
      represented phenolic ester (8) and an alcoholic ester (9) were performed. Result
      illustrated that both 8 and 9 were stable in the presence of esterase. Therefore,
      the cytotoxicity of the synthesized compounds (8-10) might be due to partial
      bioreductive activation in the cancer cells.

PMID- 17541199
TI  - Statistical optimization of tamsulosin hydrochloride controlled release pellets
      coated with the blend of HPMCP and HPMC.
AB  - The objective of the present study was to evaluate three coating parameters for
      the application of a blend of HPMCP and HPMC in ethylcellulose aqueous
      dispersions (Surelease) in order to obtain controlled release of tamsulosin
      hydrochloride. The selected independent variables, HPMCP content (X1), HPMC
      content (X2) and coating level (X(3)), were optimized with a three-factor, three
      level Box-Behnken design. The selected dependent variables were the cumulative
      percentage values of tamsulosin hydrochloride that had dissolved after 2, 3 and 5
      h. Various dissolution profiles of the drug from controlled release pellets were
      obtained. Optimization was performed for X1, X2 and X3 using the following target
      ranges; 15% < or = Y1 < or= 30%; 50% < or = Y2 < or = 65%; 80% < or = Y3 < or =
      95%. Results of the optimization procedure indicated that the optimized levels of
      HPMCP content (X1), HPMC content (X2) and coating level (X3) were 30%, 15% and
      25%, respectively. Controlled release pellets coated with the optimized
      formulation provided a release profile that was close to predicted values. In
      addition, the dissolution profiles of the controlled release pellets coated with
      the optimized formulation were similar to those of the commercial product Harunal
      capsule (f1 = 4.6, f2 = 78.7).

PMID- 17541200
TI  - New sesquiterpenes and calebin derivatives from Curcuma longa.
AB  - One novel sesquiterpene with new skeleton, (6S)-2-methyl-6-(4-hydroxyphenyl-3
      methyl)-2-hepten-4-one (1), two new bisabolane sesquiterpenes, (6S)-2-methyl-6-(4
      hydroxyphenyl)-2-hepten-4-one (2), (6S)-2-methyl-6-(4-formylphenyl)-2-hepten-4
      one (3), and two calebin derivatives, 4''-(4'''-hydroxyphenyl-3'''-methoxy)-2''
      oxo-3''-butenyl-3-(4'-hydroxyphenyl)-propenoate (4) and 4''-(4'''-hydroxyphenyl)
      2''-oxo-3''-butenyl-3-(4'-hydroxyphenyl-3'-methoxy)-propenoate (5) were isolated
      along with five known bisabolane sesquiterpenes from Curcuma longa. 1-4 were new
      compounds and 5 was a new natural product. Their structures were established by
      spectral methods.

PMID- 17541201
TI  - Development of tubulin-polymerization inhibitors based on the thalidomide
      skeleton.
AB  - We synthesized a series of compounds based on the potent tubulin-polymerization
      inhibitor 5-hydroxy-2-(2,6-diisopropylphenyl)-1H-isoindole-1,3-dione [5HPP-33
      (3)], which is structurally derived from thalidomide (1), and investigated their
      inhibitory effects on tubulin polymerization. Direct interaction between 5HPP-33
      (3) and alpha,beta-tubulin heterodimer protein was demonstrated by means of a
      surface plasmon resonance study.

PMID- 17541202
TI  - Two new xanthones isolated from the stem bark of Garcinia lancilimba.
AB  - Two new xanthones, 1,5,6-trihydroxy-6',6'-dimethyl-2H-pyrano(2',3':3,4)-2-(3
      methylbut-2-enyl)xanthone (1) and 1,6,7-trihydroxy-6',6'-dimethyl-2H
      pyrano(2',3':3,2)-4-(3-methylbut-2-enyl)xanthone (2), have been isolated from the
      stem bark of Garcinia lancilimba (Guttiferae), together with six known xanthones.
      Their structures were identified on the basis of extensive spectral evidence
      including detailed 2D NMR and HR-MS data. Two new compounds showed moderate
      inhibitory effect on human breast cancer MDA-MB-435S cell line.

PMID- 17541203
TI  - (3R,4aR,5S,6R)-6-Hydroxy-5-methylramulosin: a new ramulosin derivative from a
      marine-derived sterile mycelium.
AB  - (3R,4aR,5S,6R)-6-Hydroxy-5-methylramulosin (1) was isolated from a culture of a
      sterile mycelium, which was derived from the green alga, Codium fragile, along
      with (-)-5-methylmellein (2), (-)-5-hydroxymethylmellein (3), and (-)-(3R,4R)-cis
      4-hydroxy-5-methylmellein (4). The absolute configuration of 1 was determined by
      the NMR data along with the lactone sector rule by circular dichroism (CD).
      Compound 1 exhibited moderate cytotoxic activity against HeLa cells.

PMID- 17541204
TI  - Development of novel hemilabile Segphos P-P=O ligands.
AB  - Development of novel chiral hemilabile Segphos P-P=O ligands is described. The
      ligands are examined for enantioselective Pd-catalyzed allylic alkylation of
      cyclic allylic acetates.

PMID- 17541205
TI  - Cellulose sulfuric acid catalyzed one-pot three-component synthesis of
      imidazoazines.
AB  - Imidazoazines have been synthesized by a one-pot three-component condensation
      reaction of an aldehyde, a 2-aminoazine and an isocyanide in the presence of the
      cellulose sulfuric acid, as an effective bio-supported catalyst in excellent
      yields. The reaction work-up is simple and the catalyst can be easily separated
      from the product and reused in several times.

PMID- 17541206
TI  - Specific serotonin reuptake inhibition in major depressive disorder adversely
      affects novel markers of cardiac risk.
AB  - There exists a growing body of evidence linking depression with cardiovascular
      events, although the mechanisms responsible remain unknown. We investigated the
      role of the autonomic nervous system and inflammation in the link between
      coronary heart disease and major depressive disorder (MDD), and examined the
      cardiac risk modification following pharmacological treatment of depression. We
      measured cardiac baroreflex function, heart rate variability, pulse pressure and
      high sensitivity C-reactive protein (hsCRP), all of which have an impact on
      cardiac risk, pre- and post-treatment in 25 patients with MDD, with no history of
      coronary heart disease, and in 15 healthy subjects. Treatment consisted of
      selective serotonin reuptake inhibitors for approximately 12 weeks. No
      significant differences were observed between untreated MDD patients and healthy
      subjects in blood pressure, heart rate, baroreflex sensitivity or heart rate
      variability. Pulse pressure and hsCRP, however, were significantly elevated in
      patients with MDD prior to treatment (p=0.023 and p=0.025, respectively).
      Moreover, while pharmacotherapy was effective in alleviating depression,
      surprisingly, each of cardiac baroreflex function, heart rate variability, pulse
      pressure and hsCRP was modified (p<0.05) in a manner likely to increase cardiac
      risk. In conclusion, this study demonstrated higher pulse pressure and hsCRP
      plasma levels in patients with MDD, which might contribute to increased cardiac
      risk. Following treatment vagal activity was reduced, as indicated by reductions
      in baroreflex sensitivity and heart rate variability, accompanied by increases in
      pulse pressure and plasma hsCRP levels. Mechanisms potentially responsible for
      generating cardiac risk in patients treated with selective serotonin reuptake
      inhibitors may need to be therapeutically targeted to reduce the incidence of
      coronary heart disease in this population.

PMID- 17541207
TI  - Improvement of blood pressure control in hypertensive patients with renal
      diseases.
AB  - For hypertensive patients with renal diseases (RD), strict blood pressure (BP)
      control has been recommended in recent hypertension guidelines, such as JNC VI,
      JNC 7, WHO/ISH 1999 and ESH-ESC 2003. We assessed the current status of BP
      control and the changes of BP control before and after the publication of these
      guidelines in 489 hypertensive patients with or without RD (age, 19-89 years,
      mean 59+/-13 years) who visited the hypertension and kidney outpatient clinic at
      Kyushu University Hospital. The clinical characteristics of RD and non-RD
      patients were assessed (RD patients: age, 20-89 years, mean 60+/-13 years, n=311;
      non-RD patients: age, 19-86 years, mean 58+/-13 years, n=178). In addition, we
      compared the BP control status in 2003 to that in 1996. In 2003, the BP in RD
      patients was 134+/-16/78+/-10 mmHg and that in non-RD patients was 138+/-12/83+/
      9 mmHg. When strict BP control was defined as <130/80 mmHg, the frequency of
      strict BP control in RD patients was 28.9% in 2003. In addition, the BP levels of
      RD patients in 2003 were significantly lower than those in 1996 (134+/-16/78+/-10
      mmHg vs. 141+/-17/85+/-10 mmHg, p<0.05 for both systolic blood pressure [SBP] and
      diastolic blood pressure [DBP]), and the frequency of strict BP control in RD
      patients was higher in 2003 than in 1996 (28.9% vs. 11.8%, p<0.01). The BP levels
      of non-RD patients in 2003 tended to be lower than those in 1996 (138+/-12/83+/-9
      mmHg vs. 141+/-13/85+/-9 mmHg, n.s.). In 2003, angiotensin II receptor blockers
      (ARBs) were more frequently prescribed to RD patients than to non-RD patients.
      Furthermore, the use of ARBs was markedly increased in 2003 compared with 1996.
      In conclusion, in our outpatient clinic, BP levels in hypertensive patients with
      RD have improved in recent years, and were lower than those in hypertensive
      patients without RD, which may in part reflect the physicians' awareness of the
      importance of strict BP control in RD patients, as suggested by several recent
      hypertension guidelines.

PMID- 17541208
TI  - Usefulness of the alpha1-blocker doxazosin as a third-line antihypertensive drug.
AB  - It has been reported that a substantial majority of hypertensives receive
      insufficient blood pressure (BP) control. As combination therapy for the
      treatment of hypertension, Ca channel blockers (CCBs), angiotensin II (AII)
      receptor blockers (ARBs), and/or AII-converting enzyme (ACE) inhibitors are
      mainly prescribed, while the efficacy of alpha(1)-blockers in such combination
      therapy remains unknown. The aim of this study was to investigate the efficacy of
      a low dose of an alpha(1)-blocker added to combination therapy with CCBs and
      either ARBs or ACE inhibitors for the treatment of hypertension. Subjects were 41
      hypertensive patients (23 women and 18 men, mean age 66+/-12 years) who had been
      followed at the National Kyushu Medical Center. All patients showed poor BP
      control despite haven taken a combination of CCBs and ARBs or ACE inhibitors for
      more than 3 months. Doxazosin at a dose of 1 to 2 mg was added to each treatment
      regimen. The changes in various clinical parameters, including BP and blood
      chemistry, following the addition of doxazosin were then evaluated. The mean
      follow-up period was 170 days. BP decreased from 152+/-14/81+/-12 mmHg to 135+/
      14/70+/-11 mmHg after the addition of doxazosin at a mean dose of 1.5 mg/day
      (p<0.001). When good systolic blood pressure (SBP) control was defined as <140
      mmHg, the prevalence of patients with good SBP control increased from 24% to 61%
      (p<0.01). Similarly, the prevalence of patients with good diastolic blood
      pressure (DBP) control (<90 mmHg) increased from 78% to 98% (p<0.01). Patients
      whose SBP decreased more than 10 mmHg (n=25) showed significantly higher baseline
      SBP, serum total cholesterol and low-density lipoprotein (LDL) cholesterol levels
      compared to those who showed less SBP reduction (<10 mmHg) (n=16, p<0.01).
      Comparable BP reductions were obtained between obese (body mass index [BMI] > or
      =25, DeltaBP at 3 months: -15+/-15/-12+/-9 mmHg, n=18) and non-obese (BMI<25,
      DeltaBP: -14+/-19/-7+/-8 mmHg, n=23) patients. The results suggest that addition
      of a low dose of the alpha(1)-blocker doxazosin effectively reduces BP in
      patients taking CCBs and ARBs or ACE inhibitors. Thus, doxazosin seems to be
      useful as a third-line antihypertensive drug.

PMID- 17541209
TI  - Reduction of QTc dispersion by the angiotensin II receptor blocker valsartan may
      be related to its anti-oxidative stress effect in patients with essential
      hypertension.
AB  - QT dispersion has been reported to increase in patients with essential
      hypertension, and abnormal QT dispersion is associated with arrythmias and sudden
      cardiac death. However, whether change in QT dispersion is related to oxidative
      stress is unclear. We examined the effect of the angiotensin II receptor blocker
      valsartan on QT dispersion and the relationship between oxidative stress and QT
      dispersion in patients with essential hypertension. Hypertensive patients whose
      systolic blood pressure (SBP) was more than 140 mmHg and/or diastolic blood
      pressure (DBP) was more than 90 mmHg were treated with valsartan. Blood pressure
      was measured once a month for 6 months. The difference between the maximal and
      minimal QT intervals within a 12-lead surface ECG was measured and QT dispersion
      and QTc dispersion corrected by heart rate were obtained before and 6 months
      after treatment. Left ventricular mass (LVM) assessed by echocardiography was
      obtained at baseline and 6 months after treatment. Venous blood samples were
      obtained at baseline and 6 months after treatment to measure serum levels of
      lipoperoxidation (LPO) and type I and III procollagen. Treatment with valsartan
      significantly decreased SBP and DBP. QTc dispersion decreased significantly 6
      months after treatment with valsartan as compared to the baseline values.
      Valsartan treatment did not affect the LVM. Valsartan significantly decreased the
      abnormally high LPO levels. The changes in QTc dispersion were positively
      correlated with changes in the serum levels of LPO and with changes in DBP. The
      correlation between changes in LPO and QTc dispersion was more close than that
      between changes in DBP and QTc dispersion. In conclusion, antihypertensive
      therapy with valsartan reduces QTc dispersion and this may be related to the
      ability of valsartan to reduce oxidative stress in patients with essential
      hypertension.

PMID- 17541210
TI  - Visceral obesity in Japanese patients with metabolic syndrome: reappraisal of
      diagnostic criteria by CT scan.
AB  - To reappraise the cutoff level of abdominal circumference (AC) for diagnosis of
      visceral obesity in Japanese, we examined the association of visceral fat
      deposition with other constituents of metabolic syndrome and atherosclerotic
      cardiovascular disease (ASCD). CT was used for determination of visceral-fat area
      (VFA), subcutaneous-fat area (SFA) and AC on CT (AC(CT)) in 420 Japanese patients
      with (n=180) or without ASCD (n=240). VFA cutoff levels were calculated by
      receiver operating characteristic (ROC) analysis. AC(CT) correlated with VFA
      (r=0.828), SFA (r=0.795), and AC measured with an anthropometric tape (AC(M),
      r=0.96). The VFA cutoff levels yielding the maximum sensitivity and specificity
      to predict two or more components of metabolic syndrome were 92 cm(2) in males
      and 63 cm(2) in females, which correspond to AC(M) values of 83 cm and 78 cm,
      respectively. The male AC(M) cutoff level was similar to the AC in current
      Japanese criteria (85 cm), but the female AC(M) cutoff level was considerably
      smaller than the criteria, and this change in cutoff level increased the
      prevalence of metabolic syndrome in females three-fold. The cutoff levels of VFA
      for predicting presence of ASCD were 98 cm(2) in males and 75 cm(2) in females,
      corresponding to AC(M) values of 84 cm and 80 cm, respectively. The present
      results obtained by CT support the validity of the current Japanese criteria for
      visceral obesity in males but not in females. AC(M) of 78 cm appears to be a
      cutoff level suitable for diagnosing visceral obesity in Japanese females, though
      further confirmation is needed.

PMID- 17541211
TI  - Effects of monotherapy of temocapril or candesartan with dose increments or
      combination therapy with both drugs on the suppression of diabetic nephropathy.
AB  - We examined the effects of increasing the recommended initial doses of
      angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers
      (ARBs), or of switching to combination therapy with both drugs, on diabetic
      nephropathy. Hypertensive type 2 diabetic patients with urinary albumin excretion
      (ACR) between 100 and 300 mg/g creatinine (Cre) were assigned to the following
      five groups in which an antihypertensive drug was administered at a recommended
      initial dose for 48 weeks, and then either the dose was doubled or an additional
      drugs was added to regimen for the following 48 weeks: N, nifedipine-CR (N) 20
      mg/day (initial dose); T, ACEI temocapril (T) 2 mg/day; C, ARB candesartan (C) 4
      mg/day; T+C, T first and then addition of C; C+T, C first and then addition of C.
      ACR decreased in the T (n=34), C (n=40), T+C (n=37) and C+T (n=35) groups, but
      not in the N group (n=18). However, the anti-proteinuric effect was less in the T
      than in the C, T+C or C+T groups, while no differences existed among the latter
      three. In each group, there were significant linear relationships between
      attained BP and ACR; however, the regression lines were shifted toward lower ACR
      level in the renin-angiotensin system-inhibition groups compared with the N
      group. These results indicate that an ACEI and/or ARB is superior to a CCB in
      retarding diabetic nephropathy, while the combination of low doses of ACEI and
      ARB has effects similar to those of high-dose ARB. Even among patients treated
      with an ACEI and/or ARB, lowering BP is important.

PMID- 17541212
TI  - Relationship between cardio-ankle vascular index (CAVI) and carotid
      atherosclerosis in patients with essential hypertension.
AB  - Aortic stiffness measured by aorta-iliac or carotid-femoral pulse wave velocity
      (PWV) predicts all-cause and cardiovascular mortality. Brachial-ankle PWV (baPWV)
      has been developed as a more convenient assessment of arterial stiffness.
      However, the problem with clinical use of baPWV is that the index itself is
      closely dependent on blood pressure. Recently, a new method, termed the cardio
      ankle vascular index (CAVI), has been proposed in Japan to overcome the
      disadvantages associated with measuring PWV. However, its clinical usefulness has
      not yet been fully clarified. In the present study, we compared the usefulness of
      CAVI with that of ultrasound for evaluating atherosclerosis in patients with
      essential hypertension. CAVI was measured in 70 hypertensive patients. The intima
      media thickness (IMT), cross-sectional distensibility coefficient (CSDC),
      stiffness parameter beta, and mean diastolic (V(d)) and systolic (V(s)) flow
      velocities were evaluated by carotid ultrasound. The V(d)/V(s) ratio, an index of
      peripheral arterial resistance, was also calculated. CAVI was positively
      correlated with IMT (r=0.360, p=0.0022) and stiffness beta (r=0.270, p=0.0239)
      and negatively correlated with V(d)/V(s) (r=-0.471, p<0.0001) and CSDC (r=-0.315,
      p=0.0079). Stepwise regression analysis revealed that age (r=0.475, p<0.0001) and
      pulse pressure (r=0.492, r<0.0001) were independent determinants of CAVI. These
      results suggest that CAVI is a useful clinical marker for evaluating
      atherosclerosis and arteriolosclerosis in patients with essential hypertension.

PMID- 17541213
TI  - Reduced expression of heme oxygenase-1 in patients with coronary atherosclerosis.
AB  - Heme oxigenase-1 (HO-1) is known to be an inducible cytoprotective enzyme that
      copes with oxidative stress. However, changes in HO-1 expression and their
      association with human diseases have not been studied. To test the hypothesis
      that the capacity to upregulate HO-1 in response to oxidative stress is an
      intrinsic marker for susceptibility to coronary atherosclerosis, we assessed
      stimulation-induced change in HO-1 expression in blood cells in 110 patients who
      underwent coronary angiography, comparing the results with the extent of coronary
      atherosclerosis and (GT)(n) repeat polymorphism in the HO-1 gene promoter region,
      which is believed to affect the gene expression level. The extent of coronary
      atherosclerosis was assessed by coronary score. Mononuclear cells were incubated
      with 10 micromol/l hemin or vehicle for 4 h to maximally stimulate HO-1
      expression, then the HO-1 expression level was determined by real-time polymerase
      chain reaction (PCR). The difference between the HO-1 mRNA levels of hemin- and
      vehicle-treated cells (DeltaHO-1 mRNA) was taken as an index of the capacity to
      upregulate HO-1 mRNA. The coefficient of variance of DeltaHO-1 mRNA was 7.2%.
      Consistent with previous studies, DeltaHO-1 mRNA was significantly lower in
      patients carrying a long (GT)(n) repeat. DeltaHO-1 mRNA negatively and
      significantly correlated with the coronary score (r(2)=0.50, p<0.01). In
      conclusion, the capacity to upregulate HO-1 expression may be determined, at
      least in part, by genetics, and reduced ability to induce HO-1 may be involved in
      the mechanism of coronary atherosclerosis.

PMID- 17541214
TI  - The significance of chymase in the progression of abdominal aortic aneurysms in
      dogs.
AB  - In this study, we investigated the effect of a specific chymase inhibitor,
      NK3201, in the progression of abdominal aortic aneurysm in a dog experimental
      model. Abdominal aortic aneurysms were induced in dogs by injecting elastase into
      the abdominal aorta. NK3201 (1 mg/kg per day, p.o.) or a placebo was started 3
      days before elastase injection and continued for 8 weeks after the injection. On
      abdominal ultrasound, the aortic diameter was seen to gradually expand in the
      placebo-treated group, but not in the NK3201-treated group. Eight weeks after
      elastase injection, the ratio of the medial area to the total area in the placebo
      treated group was significantly smaller than that in the normal group, but it was
      significantly larger than that in the NK3201-treated group. In addition to
      chymase activity, angiotensin II-forming and matrix metalloproteinase-9
      activities were significantly higher in the placebo-treated group than in the
      normal group; in the NK3201-treated group, all of these activities were
      significantly decreased. On immunohistochemical analyses, there was a
      significantly greater number of chymase-positive cells in the placebo-treated
      group than in the normal group, but the number was significantly smaller in the
      NK3201-treated group than in the placebo-treated group. Thus, chymase inhibition
      may become a useful strategy for preventing abdominal aortic aneurysms.

PMID- 17541215
TI  - Azelnidipine attenuates cardiovascular and sympathetic responses to air-jet
      stress in genetically hypertensive rats.
AB  - Azelnidipine is a new dihydropyridine calcium channel blocker that causes minimal
      stimulation of the sympathetic nervous system despite its significant depressor
      effect. In the present study, we examined the effects of oral or intravenous
      administration of azelnidipine on cardiovascular and renal sympathetic nerve
      activity (RSNA) responses to air-jet stress in conscious, unrestrained stroke
      prone spontaneously hypertensive rats. Oral administration of high-dose
      azelnidipine (10 mg/kg per day) or nicardipine (150 mg/kg per day) for 10 days
      caused a significant and comparable decrease in blood pressure, but low-dose
      azelnidipine (3 mg/kg per day) did not. Air-jet stress increased mean arterial
      pressure (MAP), heart rate (HR) and RSNA. High-dose azelnidipine significantly
      attenuated the increases in MAP, HR and RSNA in response to air-jet stress while
      nicardipine did not. Low-dose azelnidipine significantly attenuated the pressor
      response with a trend of decrease in RSNA. Intravenous injection of azelnidipine
      induced a slowly developing depressor effect. To obtain a similar time course of
      decrease in MAP by azelnidipine, nicardipine was continuously infused at adjusted
      doses. Both drugs increased HR and RSNA significantly, while the change in RSNA
      was smaller in the azelnidipine group. In addition, intravenous administration of
      azelnidipine attenuated the responses of MAP, HR, and RSNA to air-jet stress; by
      comparison, the inhibitory actions of nicardipine were weak. In conclusion, oral
      or intravenous administration of azelnidipine inhibited cardiovascular and
      sympathetic responses to air-jet stress. This action of azelnidipine may be
      mediated at least in part by the inhibition of the sympathetic nervous system.

PMID- 17541216
TI  - Primary aldosteronism caused by a unilateral adrenal adenoma accompanied by
      autonomous cortisol secretion.
AB  - A 35-year-old Japanese woman was referred for further examination of persistent
      hypertension with hypokalemia. Her serum aldosterone levels were high and her
      plasma renin activity markedly suppressed. Radiological examinations revealed the
      presence of a 3-cm diameter left adrenal tumor. (131)I-adosterol was specifically
      accumulated in the left adrenal tumor, whereas the accumulation in the right
      adrenal was completely suppressed. Low-dose dexamethasone failed to suppress
      cortisol secretion although the serum cortisol levels were within the normal
      range. Urinary excretion of 17-hydroxycorticosteroids but not 17-ketosteroids was
      increased. Levels of plasma adrenocorticotropin (ACTH) and serum
      dehydroepiandrosterone sulfate (DHEAS) were decreased. Upon diagnosis of left
      aldosteronoma with autonomous secretion of cortisol, left adrenalectomy was
      performed by laparoscopy. In the resected adenoma tissues, clear cells expressed
      P450c17 protein and the ratio of CYP17/CYP11B2 mRNA evaluated by quantitative
      real-time polymerase chain reaction (PCR) was apparently higher than that of
      typical aldosteronomas. Based on the corticotropin-releasing hormone (CRH)
      loading tests, the contra-lateral adrenal functions were restored 3 months after
      surgery. These results indicate that evaluation for autonomy of cortisol
      secretion and contra-lateral adrenal function is clinically important to avoid
      the risk of adrenal failure after surgery for primary aldosteronism.

PMID- 17541217
TI  - Electrolyte disturbances in patients with hyponatremia.
AB  - OBJECT: Electrolyte abnormalities are frequently observed in patients with
      hyponatremia. The aim of this study was to determine the incidence of various
      electrolyte abnormalities encountered in hyponatremic patients admitted to an
      internal medicine clinic, as well as to investigate the possible pathogenetic
      mechanisms responsible for these abnormalities. PATIENTS AND METHODS: We
      prospectively studied 204 adult patients who either on admission to our clinic or
      during their hospitalization were found to have hyponatremia. RESULTS: Ninety-two
      patients (45.5%) had at least one additional electrolyte abnormality.
      Hypophosphatemia was the most frequent electrolyte disorder observed (35
      patients, 17%). Hypokalemia was seen in 32 patients (15.8%), hypomagnesemia in 31
      patients (15.2%) and hyperkalemia in 12 patients (5.9%). Moreover, 5 patients
      (2.5%) had hyperphosphatemia, 4 patients (1.9%) exhibited hypermagnesemia, 3
      patients (1.4%) had hypercalcemia, and 6 patients (2.9%) had true hypocalcemia.
      There were no statistically significant differences regarding the incidence of
      these electrolyte abnormalities (as a whole) between the main subgroups of
      hyponatremic patients (diuretic-induced, syndrome of inappropriate antidiuretic
      hormone, hypovolemia-induced and edematous state-related). However, hypokalemia
      and hypomagnesemia were more frequently observed in patients with diuretic
      induced hyponatremia, while hyperkalemia was more frequently seen in edematous
      state-related hyponatremia. CONCLUSIONS: Additional electrolyte abnormalities are
      frequently encountered in patients with hyponatremia of any origin admitted to an
      internal medicine clinic.

PMID- 17541218
TI  - Significance of serum uric acid in patients with chronic respiratory failure
      treated with non-invasive positive pressure ventilation.
AB  - PURPOSE: The aim of the study was to evaluate serum uric acid (UA) levels before
      and after non-invasive positive pressure ventilation (NPPV) to assess the utility
      of serum UA as an indicator of acute exacerbation of chronic respiratory failure
      (CRF) in patients treated with NPPV. METHODS: We analyzed change in the serum UA
      level in 29 patients with CRF due to restrictive thoracic disease and treated
      with NPPV. RESULTS: After NPPV therapy, PaO2 was significantly increased and
      PaCO2 was significantly decreased in all patients. Sixty-two percent of patients
      (18 of 29) showed a decreased serum UA/creatinine (Cr) ratio after NPPV therapy,
      but, overall, there was no significant change in serum UA/Cr (P=0.0688). The
      change in serum UA/Cr was not correlated with the changes in PaO2 and PaCO2 after
      NPPV. When we compared patients in whom serum UA/Cr decreased (n=18) with
      patients in whom serum UA/Cr did not decrease (n=11), there were significantly
      fewer patients who suffered CRF exacerbation in the group with a decrease
      (P=0.0021). Furthermore, the cumulative proportion (Kaplan-Meier) of patients who
      did not suffer exacerbation of CRF was significantly higher in the group in which
      serum UA/Cr decreased (P=0.0003). CONCLUSIONS: Our data suggest that serum UA may
      be a useful clinical indicator of CRF exacerbation in patients treated by NPPV.

PMID- 17541219
TI  - Neutrophil elastase as a predicting factor for development of acute lung injury.
AB  - OBJECTIVE: To determine whether the development of acute lung injury (ALI) and
      acute respiratory distress syndrome (ARDS) associated with systemic inflammatory
      response syndrome (SIRS) can be predicted by the plasma neutrophil elastase
      level. PATIENTS AND METHODS: Patients were sequentially enrolled after obtaining
      informed consent. Twenty-three adult patients with SIRS were classified into the
      following groups; SIRS alone (5 patients), Group A of ALI/ARDS with SIRS (9
      patients) that did not require mechanical ventilation, and Group B of ALI/ARDS
      with SIRS (9 patients) that required mechanical ventilation. Blood samples were
      obtained after the diagnosis of SIRS, and the sequential sampling was performed.
      RESULTS: The plasma neutrophil elastase level was significantly elevated in all
      patient groups as compared with healthy controls (43.7+/-5.4 ng/ml). The elastase
      levels in SIRS alone, Group A of ALI/ARDS, and Group B of ALI/ARDS were 126.9+/
      11.0 ng/ml, 316.2+/-68.9 ng/ml, and 458.4+/-132.8 ng/ml, respectively. The
      elastase level in ALI/ARDS with SIRS was significantly greater than that in SIRS
      alone. The maximal level in 13 of 18 patients with ALI/ARDS with SIRS was more
      than 220 ng/ml. The level in all patients with SIRS alone was consistently less
      than 220 ng/ml over the study period. The serum levels of inflammatory cytokines
      were elevated in these patients, but no statistical significance was detected
      among the groups. CONCLUSION: The critical level of plasma neutrophil elastase is
      220 ng/ml, and the SIRS patients with more than 220 ng/ml neutrophil elastase are
      highly likely to develop ALI/ARDS.

PMID- 17541220
TI  - Small intestinal follicular lymphoma with multiple tumor formations diagnosed by
      double-balloon enteroscopy.
AB  - Follicular lymphoma of the small intestine remains relatively rare, especially in
      its early stage. Recently, double-balloon endoscopy has enabled observation of
      the entire small intestine. We describe a case of follicular lymphoma with
      multiple lesions in the small intestine detected by double-balloon endoscopy. The
      patient showed multiple whitish granules in descending portion of the duodenum on
      screening esophagogastroduodenoscopy, which were subsequently diagnosed as
      follicular lymphoma by immunohistochemistry. Endoscopic examination of the entire
      small intestine revealed multiple follicular lymphoma tumors in inferior portion
      of the duodenum and in the proximal jejunum. Double-balloon endoscopy is useful
      for evaluating tumor distribution of follicular lymphoma.

PMID- 17541221
TI  - Hepatocellular carcinoma with peritoneal dissemination which was regressed during
      vitamin K2 and vitamin E administration.
AB  - A 65-year-old man with positive anti-hepatitis C antibody and chronic renal
      failure was diagnosed as having a ruptured hepatocellular carcinoma (HCC) based
      on computed tomography (CT). The patient underwent transcatheter arterial
      embolization (TAE) for the HCC. After one more session of TAE, the patient
      underwent surgery. But HCC seeding peritoneally was pointed out. Vitamin K2 and
      vitamin E were administered as a conservative treatment. Six months after
      starting vitamins K2 and E, the primary tumor did not increase in size and
      intraperitoneal dissemination disappeared on CT with a significant decrease of
      alpha-fetoprotein. Even though this is only one case, combination therapy of
      vitamin K2 and E may induce growth suppression of HCC.

PMID- 17541222
TI  - Rescue therapy with tacrolimus for a patient with severe ulcerative colitis
      refractory to combination leukocytapheresis and high-dose corticosteroid therapy.
AB  - A19-year-old man complaining of severe diarrhea and hematochezia was admitted to
      our hospital. Endoscopic findings and laboratory data revealed that he had
      ulcerative colitis (UC). Despite combination therapy with high-dose
      corticosteroids and intensive granulocytapheresis, his condition did not improve.
      Therefore, we initiated tacrolimus therapy. Intravenous administration of
      tacrolimus with a trough level of 10 to 15 ng/ml relieved his abdominal symptoms
      within 1 week. The patient experienced no UC relapse 1 year after treatment with
      oral tacrolimus. Tacrolimus is a promising therapy for patients with UC
      refractory to the combination of high-dose corticosteroids and leukocytapheresis.

PMID- 17541223
TI  - Pulmonary capillary bleeding in a patient with severe left ventricular failure
      after acute myocardial infarction under anti-thrombotic therapy.
AB  - A 52-year-old man who was admitted for cardiogenic shock after acute myocardial
      infarction developed severe left ventricular dysfunction despite reperfusion
      therapy with coronary stents. After the 40th hospital day, he started to have
      cough and pulmonary infiltrates. Antimicrobial therapies and subsequent
      prednisolone for bronchiolitis obliterans organizing pneumonia were ineffective.
      Bronchoscopic examination revealed diffuse pulmonary bleeding and exudation of
      hemosiderin-containing macrophages in bronchial lavage fluid. Pulmonary capillary
      bleeding has been reported in the terminal stage of patients with mitral stenosis
      in the pre-cardiac surgery era. This complication reemerges in patients with
      severe heart failure receiving intensive anti-coagulation therapy after
      implanting a sirolimus-eluting coronary stent.

PMID- 17541224
TI  - Subcutaneous injection of heparin calcium controls chronic disseminated
      intravascular coagulation associated with inoperable dissecting aortic aneurysm
      in an outpatient clinic.
AB  - BACKGROUND: Chronic disseminated intravascular coagulation (DIC) is a rare but
      critical complication of aortic aneurysm, and can represent a difficult long-term
      management problem. Although surgical correction is the treatment of choice,
      alternative therapy is required for inoperable patients. RESULTS: We report
      herein a case of acute exacerbation of chronic DIC with inoperable dissecting
      aortic aneurysm, which was recurrent and resistant to regular treatment.
      Intermittent subcutaneous self-injection of heparin calcium 15,000 units per day
      achieved stabilization of coagulation and fibrinolytic parameters and relief of
      the bleeding tendency. CONCLUSION: Subcutaneous heparin injection can be an
      alternative treatment for long-term management of chronic DIC associated with
      inoperable aortic dissection, beneficial for providing good symptomatic control
      on an outpatient basis.

PMID- 17541225
TI  - Rapid formation of Aspergillus mycetoma in a patient receiving corticosteroid
      treatment. Serial radiographic observation over two months.
AB  - This study presents the case of rapidly progressing pulmonary aspergillosis in a
      47-year-old woman who had healed cavitations of pulmonary tuberculosis in the
      right upper lobe. She had been treated for pulmonary tuberculosis seven years
      prior to admission. The initial manifestations of the disease on admission
      included cough, dyspnea, hemoptysis, pulmonary infiltrate, and renal failure. As
      anti-myeloperoxidase anti-neutrophil cytoplasmic antibodies (MPO-ANCA) were
      positive, she was diagnosed with ANCA-associated vasculitis and treated with
      corticosteroids. This treatment resulted in remission of the vasculitis. However,
      she developed new pulmonary symptoms and an enlarged cavitary lesion associated
      with the rapid formation of a fungal, ball-shaped shadow that was serially
      observed by radiological analysis. Pulmonary resection was finally performed
      because of acute progressive respiratory failure due to massive recurrent
      hemoptysis. A subsequent pathological analysis revealed a mass of hyphae with
      acute-angle branching, features consistent with Aspergillus, within the cavitary
      lesion, and she was diagnosed with pulmonary aspergillosis. The rapid development
      of pulmonary aspergillosis associated with the formation of an Aspergillus
      mycetoma should be attributed to the loss of normal immune mechanisms due to
      immunosuppressive treatment.

PMID- 17541226
TI  - Angioimmunoblastic T-cell lymphoma developed with lymphocytic pleural effusion.
AB  - Angioimmunoblastic T-cell lymphoma (AILT) is a rare variant of nodal and
      aggressive lymphoma. It is sometimes difficult to distinguish AILT from reactive
      lymphoid hyperplasia from the histopathological aspect. We report a case of AILT
      which developed with bilateral pleural effusion. The effusion consisted
      predominately of small lymphoid cells. Analyses of the effusion showed trisomy 3,
      and rearranged bands of TCR beta gene. Flow cytometry showed a very small amount
      of CD10-positive cells. Although we could not further identify the tumor cells in
      this case, analysis of pleural effusion cells will increase our understanding of
      the pathogenesis and the pathophysiology of AILT.

PMID- 17541227
TI  - Dropped head sign as the only symptom of myasthenia gravis.
AB  - Neck extensor muscle weakness and the dropped head sign are associated with
      various neuromuscular disorders. However, these symptoms are comparatively rare
      in myasthenia gravis (MG). We report a MG case that presented with dropped head
      sign as the main symptom. A 55-year-old man developed subacute weakness of the
      neck extensor muscle and presented with dropped head. We established a diagnosis
      of MG based on the results of an edrophonium test and a voluntary single fiber
      electromyogram (vSFEMG), and a high serum antiacetylcholine receptor antibody
      level. This patient was treated with pyridostigmine and his neurological symptoms
      improved. There are reported cases of dropped head sign as the first symptom of
      MG, however, in those cases, other muscles showed weakness during the first few
      months after onset. In the present case, throughout the clinical course no other
      symptoms outside of dropped head sign were seen.

PMID- 17541228
TI  - Myasthenia gravis with concomitant severe paraspinal muscle degeneration and
      mitochondrial DNA4977 deletion.
AB  - Recent reports have discussed the many causes of dropped head syndrome and bent
      spine syndrome. We described a case of myasthenia gravis with concomitant severe
      degeneration of spinal muscle, mitochondrial DNA4977 deletion and sensorineural
      deafness. These associations were thought to be independent, however this is an
      important case to consider the etiology of bent spine syndrome.

PMID- 17541229
TI  - Two cases of spinocerebellar ataxia accompanied by involvement of the skeletal
      motor neuron system and bulbar palsy.
AB  - We report two patients with spinocerebellar ataxia (SCA) with cranial and spinal
      motor neuron involvement. They initially presented with cerebellar ataxia,
      followed by bulbar palsy and limb motor neuron sign. One of the patients had a
      brother with allied disorder. SCA type 1 (SCA1), SCA3 and SCA6 have been reported
      to involve the motor neuron system, but they were excluded by DNA analyses in the
      present two patients. These two patients may form a distinct disease entity among
      SCAs.

PMID- 17541230
TI  - LAMP-2 positive vacuolar myopathy with dilated cardiomyopathy.
AB  - We report a 46-year-old male patient with late-onset vacuolar myopathy and
      dilated cardiomyopathy. Acid maltase activity of the muscle was normal, but the
      biopsied muscle specimen stained for lysosome-associated membrane protein-2 (LAMP
      2), which has recently been reported to be deficient in muscles of patients with
      Danon disease. The clinical features of the patient are distinct from X-linked
      myopathy with excessive autophagy, infantile autophagic vacuolar myopathy and
      autophagic vacuolar myopathy with late-onset and multiorgan involvement (Kaneda).

PMID- 17541231
TI  - Herpes simplex virus type-1 meningoencephalitis showing disseminated cortical
      lesions.
AB  - We report a 41-year-old man with meningoencephalitis associated with herpes
      simplex virus type 1 (HSV-1). The patient developed fever, headache and dysuria
      followed by generalized convulsion and neck stiffness, and the CSF showed
      pleocytosis. The titers of enzyme-linked immunosorbent assay against HSV measured
      6 days after onset showed a significant rise; IgG antibody 4.89 (<0.2) and IgM
      antibody 1.45 (<0.8) in CSF, IgG antibody 46.1 (<2.0) and IgM antibody 1.76
      (<0.8) in the serum. The antibody index for IgG was 0.50, and that for IgM was
      4.2. CFS neutralization test showed HSV-1 antibody of x16 and HSV-2 antibody of
      <x4. MRI showed atypical features: disseminated cortical lesions without massive
      hemispheric involvement. All of the cortical lesions were small and appeared to
      be located in the gray matter. The patient recovered with acyclovir. This report
      demonstrates that disseminated encephalitis can be a feature of acute HSV-1
      infection.

PMID- 17541232
TI  - C4B deficiency associated with membranoproliferative glomerulonephritis.
AB  - A 10-year-old girl was noted to have microscopic hematuria and proteinuria in
      1986. As her urinary abnormalities were persistent, she underwent a renal biopsy
      on 4 occasions until 2003. Although the appearances of the renal biopsies were
      strongly suspicious of systemic lupus erythematosus, she never exhibited specific
      autoantibodies or distinctive symptoms. She received corticosteroid therapy and
      the urinary findings responded. The 4th component of complement remained low
      during the period of the observation. Both genotyping and allotyping analysis
      revealed complete C4B deficiency. Some case reports have mentioned renal disease
      associated with C4B deficiency and we consider the nephropathy in this case to be
      related to the C4B deficiency.

PMID- 17541233
TI  - Anti-interleukin-6 receptor antibody (tocilizumab) treatment of multicentric
      Castleman's disease.
AB  - We report three cases of multicentric Castleman's disease (MCD) successfully
      treated with anti-interleukin-6 receptor antibody (tocilizumab). Tocilizumab was
      administered intravenously at a dose of 8 mg/kg every 2 weeks. In each case,
      tocilizumab alleviated symptoms, including generalized fatigue, pyrexia, and
      alleviated biochemical abnormalities, including anemia, hypoalbuminemia,
      hypergammaglobulinemia, and increased C-reactive protein (CRP). Side effects
      included hypercholesterolemia, acute pyelonephritis, mild inflammation of the
      parotid glands, and upper respiratory system inflammation. Other severe side
      effects were not observed. These results indicate that tocilizumab is effective
      for the treatment of MCD. This is the first report on tocilizumab efficacy for
      Castleman's disease after approval for use for Castleman's disease.

PMID- 17541234
TI  - Invasive pulmonary aspergillosis with hematological malignancy caused by
      Aspergillus terreus and in vitro susceptibility of A. terreus isolate to
      micafungin.
AB  - A 35-year-old man developed invasive pulmonary aspergillosis (IPA) with severe
      neutropenia after umbilical cord stem cell transplantation for chronic
      myelogenous leukemia. Filamentous fungus isolated from his sputum was identified
      as Aspergillus terreus. Despite systemic amphotericin B (AMPH) administration,
      IPA progressed. However, intravenous administration of micafungin (MCFG) and oral
      itraconazole improved clinical data and symptoms, although he later died of
      massive hemoptysis. Examination of the in vitro susceptibility of this A. terreus
      isolate to MCFG revealed a good minimum inhibitory concentration and good time
      kill assay results compared to AMPH. Thus, MCFG might be useful for IPA caused by
      A. terreus.

PMID- 17541235
TI  - Adenocarcinoma arising in a mediastinal enteric cyst.
AB  - A 39 year-old male was admitted to our hospital because of relapsing episodes of
      pneumonia. His chest roentgenogram showed a consolidated shadow and cavity
      formation in the left lower lobe. During a left lower lobectomy an enteric cyst
      in the posterior mediastinum involving lung was found. This cyst in the lung
      contained normal gastric parietal cells and pancreatic tissue, and was surrounded
      by adenocarcinoma characteristic of gastric cancer. This is a rare case in which
      an adenocarcinoma arise from an enteric cyst in the mediastinum.

PMID- 17541236
TI  - Thrombotic microangiopathy due to malignant hypertension following corticosteroid
      therapy for microscopic polyangitis.
AB  - A 78-year-old woman was treated with 40 mg of prednisolone for microscopic
      polyangitis, and favorable effects were observed. However, her blood pressure
      increased and she developed severe thrombocytopenia. Thrombotic microangiopathy
      (TMA) due to malignant hypertension was suspected and she was treated with an
      angiotensin-converting enzyme inhibitor; her platelet count then rose. She showed
      a close temporal relationship between initiation of corticosteroid therapy and
      the onset of TMA. Corticosteroid therapy should be used with caution in patients
      with underlying vascular endothelial damage.

PMID- 17541237
TI  - Serum level of macrophage migration inhibitory factor in Helicobacter pylori
      infected patients.

PMID- 17541238
TI  - Are subjective memory complaints mandatory for the diagnosis of mild cognitive
      impairment?

PMID- 17541239
TI  - Spontaneous hemorrhage from renal angiomyolipoma presenting with fever of unknown
      origin.

PMID- 17541241
TI  - [Appropriate usage of antibiotics by therapeutic drug monitoring].
AB  - Aminoglycosides are mainly distributed in the extracellular fluid, so when they
      are given to neonates who have a large amount of extracellular fluid, their
      distribution is increased. In our data, the volume of distribution (Vd) of
      Arbekacin in the neonates was twice that of the adults, 0.54 l/kg. Therefore, the
      dose per weight of aminoglycosides to the neonates should be increased more than
      to the adults. In the renal function of the neonates, differentiation of the
      nephron is completed within 36 weeks after conception, but it is functionally
      immature. In our data, renal drug excretion increased rapidly in the post
      conceptional ages (PCAs) of 34-35 weeks. Consequently, we based the Arbekacin
      administration schedule for the neonates on the PCAs. There is excellent
      correlation between serum level of vancomicin (VCM) and dose x serum creatinine
      (Scr)/weight in the haemodialysis patients, suggesting that we can use weight and
      Scr to set the VCM administration schedule for these patients. We also
      established on administration schedule of Teicoplanin for the haemodialysis
      patients. In this article, we present the TDM analysis result of the antibiotics
      in our hospital.

PMID- 17541242
TI  - [PK/PD analysis and proper dosage of antimicrobial agents for effective and safe
      treatment of infectious diseases].
AB  - The dosage of antimicrobial agents from PK/PD analysis is now considered
      important for using these agents effectively and safely. In this paper, I will
      discuss the proper dosage of antimicrobial agents from the point of PK/PD
      analysis. I will also discuss the correlation between the safety profile and
      pharmacokinetic parameters of the agents. It is my hope that all pharmacists will
      understand the proper use of antimicrobial agents and thus will assure the
      effective and safe treatment of patients with infectious diseases.

PMID- 17541244
TI  - [Pharmaceutical Common Achievement Test: computer-based testing (CBT)].
AB  - A six-year course of pharmaceutical education including long-term on-site
      practical training (pharmacy clerkship) started in the 2006 academic year in
      Japan. To develop good pharmacists in response to social needs, all university
      education programs are conducted in accordance with the Model Core Curriculum for
      Pharmaceutical Education in Japan and the Model Core Curriculum for Pharmacy
      Practical Experience. In addition to the two core curricula, each university also
      implements the Pharmaceutical Common Achievement Test, which is a combination of
      computer-based testing (CBT) and objective structured clinical examination
      (OSCE). The CBT is primarily used to evaluate the student's knowledge, with the
      student answering 310 questions chosen randomly from a pool on the computer,
      essentially based on the contents of the model core curriculum. On the other
      hand, the OSCE is used to evaluate the skills and attitudes of the student. Only
      students who pass the Common Achievement Test can move on to a pharmacy clerkship
      in a clinical setting. We review the history and present status of CBT
      preparation and outline the CBT. Upon examining the present situation of the CBT,
      it is required for the pharmaceutical scientists concerned to prepare high
      quality problems based on the model core curriculum education system.

PMID- 17541245
TI  - [Major challenge in preparation for Practical On-site Training--creation of
      evaluation program].
AB  - The Conference for Studying the Pharmacopedical Curriculum was inaugurated in
      2001, sponsored by the Pharmaceutical Society of Japan. In April 2002, the draft
      of a new model curriculum was presented to all pharmaceutical schools and key
      organizations. Finally, the conference drafted the Model Core Curriculum for
      Pharmaceutical Education and the Practical On-site Training and Graduation
      Training Curriculum. The Model Core Curriculum for Practical On-site Training was
      drafted in 2003. The Committee for the Educational Guidance System in Practical
      On-site Training, established in 2004 by the Pharmaceutical Society of Japan, is
      a committee for the development of the guidance system for practical on-site
      training. This committee held two workshops to create an evaluation program for
      specific behavioral objectives in the Model Core Curriculum for Practical On-site
      Training. The evaluation program has not yet been proposed. Evaluation programs
      for eight units presented in the Model Core Curriculum for Practical On-site
      Training have been proposed. A verification trial has already been performed in
      several schools/colleges/universities. The evaluation program of the remaining
      units is scheduled. This symposium introduces the development of the evaluation
      program and proposes the performance of verification trials.

PMID- 17541246
TI  - [Accreditation of pharmacy education in Japan].
AB  - The need of society for professional pharmacists has been growing. In response to
      social needs, the six-year pharmacy education system, which is mandatory for
      registration for the examination to become a licensed pharmacist, was established
      under the Pharmacists Law and the Fundamentals of Education Act in academic year
      2006. In accordance with the amendment of the Fundamentals of Education Act, it
      is obligatory to develop an accreditation system for six-year pharmacy education
      in Japan. The Committee for the Accreditation System for Pharmacy Education in
      Japan was set up under the Committee of Pharmacy Education Reform of the
      Pharmaceutical Society of Japan to investigate the accreditation system and to
      draw up a draft of the evaluation standard. The draft was distributed at the end
      of January 2007 to request feedback from each pharmaceutical university and will
      be revised within the next few years simultaneously with trials for
      accreditation.

PMID- 17541247
TI  - [Perspectives on educational reform of pharmaceutical science].
AB  - The six-year system of pharmaceutical education in Japan has started this fiscal
      year, based on the amendment to the two related laws, namely "The Pharmacist Law"
      and "The Fundamental Law of Education". This new system is expected to produce
      future pharmacists who will be able to contribute to raising the level of
      pharmaceutical care in the national medical care system. The practical training
      for pharmaceutical care that future pharmacists will have is an important safety
      measure for pharmaceuticals in the medical care system, so that producing
      qualified pharmacists would be supported by the people. For this purpose we will
      help to improve the training system, and the circumstances where future
      pharmacists will be able to realize their ideal pharmaceutical care.

PMID- 17541248
TI  - [S-adenosyl-L-homocysteine hydrolase as an attractive target for antimicrobial
      drugs].
AB  - S-Adenosyl-L-homocysteine (SAH) hydrolase catalyzes breakdown of SAH, which
      arises after S-adenosylmethionine-dependent methylation, into adenosine and
      homocysteine. The enzyme activity is required for both metabolic pathway of
      sulfur-containing amino acids and a variety of biological methylations. Because
      of the essential roles of SAH hydrolase for living cells, inhibitors of SAH
      hydrolase are expected to be antimicrobial drugs, especially for viruses and
      malaria parasite. Our research focused on the development of new antimalarials
      based on the SAH hydrolase inhibition. Malaria parasite employs SAH hydrolase of
      itself for coping with the toxicity of SAH, so that the target offers
      opportunities for chemotherapy if structural differences are exploited between
      the parasite and human enzymes. In vitro screens of nucleoside analogs resulted
      in moderate but selective inhibition for recombinant SAH hydrolase of malaria
      parasite, Plasmodium falciparum, by 2-position substituted adenosine analogs.
      Similar selectivity was observed in the growth inhibition assay of cultured
      cells. Following crystal structure analysis of the parasite SAH hydrolase
      discovered an additional space, which is located near the 2-position of the
      adenine-ring, in the substrate binding pocket. Mutagenic analysis of the amino
      acid residue forming the additional space confirmed that the inhibition
      selectivity is due to the difference of only one amino acid residue, between
      Cys59 in P. falciparum and Thr60 in human. For developing antimalarial drugs, it
      might be suitable to select target from pathways that are present in the parasite
      but absent from humans; nevertheless, even if the target was common in parasite
      and host, slight structural difference such as single amino acid variation is
      likely to be available for improving inhibitor selectivity.

PMID- 17541249
TI  - [Targeted molecular strategies for cancer therapy based on the blockage of
      oncogenic pathways in human tumor cells].
AB  - Constitutive activation of the extracellular signal-regulated kinase (ERK) and/or
      phosphatidylinositol-3 kinase (PI3K)/Akt signaling pathways is associated with
      neoplastic transformation of a variety of human tumor cells. Treatment of such
      tumor cells with agents that specifically inhibit the activity of mitogen
      activated protein kinase/ERK kinase (MEK) or PI3K completely suppresses their
      proliferation. However, treatment of cells with these inhibitors leads to only a
      modest increase in apoptotic cell death. Efficient induction of apoptosis is
      essential for the development of effective cancer chemotherapy. Therefore, we
      have examined whether specific blockade of these two signaling pathways affects
      the efficacy of the induction of apoptosis by various anti-cancer agents in tumor
      cells. We found that MEK inhibitors markedly enhance the efficacy of histone
      deacetylase inhibitors to induce the generation of reactive oxygen species and
      apoptosis. This effect was only observed in tumor cells in which the ERK pathway
      was constitutively activated. Furthermore, we found that PI3K inhibitors
      selectively and markedly enhanced the efficacy of the induction of apoptosis by
      doxorubicin. This latter effect was only detected in tumor cells in which the
      PI3K/Akt pathway was constitutively activated and in which the p53 pathway was
      functional. These combination treatments provide an efficient chemotherapeutic
      strategy for the treatment of tumor cells in which the ERK pathway or PI3K/Akt
      pathway is constitutively activated. This review gives an overview of the
      development of new targeted molecular strategies for cancer therapy based on the
      suppression of the activity of oncogenic pathways involved in the proliferation
      or survival of tumor cells.

PMID- 17541250
TI  - Determination of tetraconazole and diniconazole fungicide residues in tomatoes
      and green beans by capillary gas chromatography.
AB  - A sensitive gas chromatographic method using an electron-capture detector (ECD)
      has been developed for the determination of tetraconazole and diniconazole
      fungicide residues in tomatoes and green beans. The developed method consists of
      extraction with methanol, partition with methylene chloride, and column
      chromatographic clean-up, followed by capillary gas chromatographic
      determination. The recoveries of both fungicides were greater than 90% for both
      plant samples. The limits of determination of the method were 0.001 ppm for both
      fungicides. The method was applied to determine residues and the rate of
      disappearance of tetraconazole and diniconazole from tomatoes and green beans
      [open field treatment, 50 cc of Domark 10% EC (emulsifiable concentrate), and 35
      cc of Sumi-eight 5% EC; both for 100 l of water]. The fungicides incorporated
      into the plants decreased rapidly with a half-life around 3 days for diniconazole
      and from 4.5 to 6.5 days for tetraconazole. No residues could be detected in the
      plants during the period of study of 21 days after field application. Hence, the
      plants could be used safely after that period of time.

PMID- 17541251
TI  - Preventive effects of low-dose dexamethasone for delayed adverse events induced
      by carboplatin-based combination chemotherapy.
AB  - We performed a retrospective study to examine the protective effect of low-dose
      dexamethasone (DEX) on delayed adverse events induced by carboplatin (CBDCA)
      based combination chemotherapy in patients with thoracic tumors. Low-dose DEX (4
      8 mg/day) was administered on day 1 and after, in addition to a serotonin 5-HT3
      receptor antagonist. The acute adverse events (day 1) were well controlled in the
      patients with or without co-treatment of DEX. On the other hand, the delayed
      nausea, emesis, anorexia, and fatigue after day 2 failed to be controlled by 5
      HT3 antagonist alone. Co-treatment with DEX significantly suppressed the grade of
      the delayed adverse events during days 2-10. The mean ratio of complete
      protection during days 2-10 were significantly higher in the DEX-treated group
      compared with the non-DEX-treated group. These results reveal that low-dose DEX
      is a clinically effective treatment for the prevention of delayed adverse events
      induced by CBDCA-based combination chemotherapy.

PMID- 17541252
TI  - Quantification of cibenzoline by enzyme-linked immunosorbent assay.
AB  - We have developed an enzyme-linked immunosorbent assay (ELISA) suitable for
      routine monitoring of serum levels of cibenzoline. Anti-cibenzoline antibody was
      obtained by immunizing rabbits with cibenzoline conjugated with bovine serum
      albumin using N-(4-maleimidobutyryloxy)succinimide as a heterobifunctional
      coupling agent. An enzyme marker was prepared by coupling 2,2-diphenylethylamine
      with beta-D-galactosidase using glutaraldehyde. The detection limit of
      cibenzoline by ELISA was approximately 640 pg/ml with 50-microl samples. Cross
      reactivity data showed that the antibody well recognizes both the diphenyl and
      cyclopropyl moieties, and is thus specific enough to the structure of
      cibenzoline. The values for the cibenzoline concentrations detected using this
      assay were comparable with those detected using HPLC. There was a good
      correlation between the values determined by the two methods. Moreover, ELISA was
      about 15-fold more sensitive in detecting cibenzoline at lower concentrations.
      Using this assay, drug levels were easily measured in the serum of rabbits after
      oral administration of cibenzoline at a single dose of 3 mg/kg.

PMID- 17541253
TI  - Possible involvement of insulin, endogenous opioids and calcitonin gene-related
      peptide in remote ischaemic preconditioning of the brain.
AB  - The present study has been designed to investigate the role of insulin,
      endogenous opioids and calcitonin gene related peptide (CGRP) on remote
      mesenteric ischaemic preconditioning induced reversal of global cerebral
      ischaemia-reperfusion injury in mice. Bilateral carotid artery occlusion of 10
      min followed by reperfusion for 24 hour was employed in present study to produce
      ischaemia and reperfusion induced cerebral injury in mice. Cerebral infarct size
      was measured using triphenyltetrazolium chloride staining. Short-term memory was
      evaluated using elevated plus maze. Inclined beam walking and resistance to
      lateral push response, tests were employed to assess motor incoordination.
      Bilateral carotid artery occlusion followed by reperfusion produced cerebral
      infarction and impaired short-term memory, motor co-ordination and lateral push
      response. A preceding episode of mesenteric artery occlusion for 15 min and
      reperfusion of 15 min (remote mesenteric ischaemic preconditioning) prevented
      markedly, ischaemia-reperfusion-induced cerebral injury measured in terms of
      infarct size, loss of short-term memory, motor coordination and lateral push
      response. Anti-insulin serum, naloxone (an opioid receptor antagonist) and alpha
      CGRP (8-37) (a selective CGRP receptor blocker) attenuated the neuroprotective
      effect of remote mesenteric ischaemic preconditioning. It may be concluded that
      neuroprotective effect of remote mesenteric ischaemic preconditioning probably is
      mediated through insulin, endogenous opioids and CGRP released as a consequence
      of mesenteric ischaemia and reperfusion in mice.

PMID- 17541254
TI  - Contributions of pharmacists through the promotion of proper drug use.
AB  - The contents of pharmacist interventions, which were carried out by the ward
      pharmacists in their routine pharmacy service activities, were sorted and
      analyzed to evaluate the contributions of pharmacists. In the ward where
      pharmacists were stationed, there were a total of 196 cases of pharmacist
      intervention. The prescription was changed in 170 cases, giving a rate of
      prescription change of 86.7%. The breakdown of the pharmacist intervention was as
      follows: "efficacy/safety", 106 cases, followed by "dosage regimen" (48 cases)
      and "compliance" (10 cases). Cost savings achieved during the investigation
      period were calculated to be 440,639 yen, and cost avoidance was valued at
      1,941,847-3,883,695 yen using the Diagnosis Procedure Combination (DPC). The
      results of the present investigation showed that pharmacists contribute to
      through not only their pharmacy services, but also through the promotion of
      proper drug use and risk management, thereby contributing to hospital management
      through cost savings and avoidance.

PMID- 17541255
TI  - [Monitoring sheet covering long-term chemotherapy to predict individual adverse
      reaction patterns for patients with gynecologic chemotherapy].
AB  - Monitoring the adverse reaction patterns specific to individual patients is
      important to avoid subsequent reactions. Gynecologic cancer chemotherapy is often
      implemented repeatedly with an altered protocol during prolonged terms. The
      purpose of this study was to develop and assess the efficacy of a worksheet that
      pharmacists can use to analyze adverse reaction patterns in individual patients
      with gynecologic chemotherapy. The worksheet which we developed consisted of
      multiple sections. One section is for necessary drug information for the proper
      use of antineoplastic agents. Another section is for the following items recorded
      by the pharmacists: a) patients' basic information such as stage of disease and
      protocol, b) state of implementation and break of chemotherapy and supportive
      therapy on calendar, and c) laboratory data and symptoms. We arranged the last
      item below the calendar and enabled pharmacists to easily assess individual
      adverse reactions coupled with the treatment course. Reviews of the developed
      worksheet indicated that the worksheet led to the convenient detection of
      individual adverse reaction patterns and effective prevention of additional
      adverse reactions. This monitoring sheet covering long-term chemotherapy which
      was designed to predict individual adverse reaction patterns will improve the
      individualization and safety of gynecologic chemotherapy.

PMID- 17541256
TI  - Subpopulations of somatotropes with differing intracellular calcium concentration
      responses to secretagogues.
AB  - Multiple secretagogues stimulate the release of growth hormone (GH). The present
      studies examined the ability of chicken somatotropes to respond to GH
      secretagogues with increased intracellular calcium concentrations ([Ca2+]i). It
      was hypothesized that there are subsets of the somatotrope population with
      different responsiveness to the various secretagogues. Somatotropes were
      identified and distinguished from other adenohypophyseal cells, by their unique
      ability to respond to GH-releasing hormone with increased [Ca2+]i with
      immunocytochemistry used as a post-hoc confirmatory test. Large increases in
      [Ca2+]i (222 +/- 16 nM) were evoked by thyrotropin-releasing hormone in only 73%
      of the somatotropes. Similarly, [Ca2+]i was increased by perifusion with
      pituitary adenylate cyclase-activating peptide in 85% and by leptin but only in
      51% of somatotropes. Ghrelin acutely increased [Ca2+]i in only 21% of
      somatotropes. Perfusion with gonadotropin-releasing hormone elevated [Ca2+]i, but
      in only 40% of somatotropes. The kinetics of calcium transients and the magnitude
      of the response differed from those observed in the presumptive gonadotropes. It
      is concluded that there are subsets of the somatotrope population in the anterior
      pituitary gland with differences in their ability to respond to various
      secretagogues.

PMID- 17541257
TI  - Effective treatment of locally advanced endocrine tumors of the pancreas with
      chemoradiotherapy.
AB  - BACKGROUND/AIMS: The use of chemoradiation in the management of locally advanced
      pancreatic endocrine tumors has not been reported in the medical literature.
      Patients with unresectable tumors are often included in trials of systemic
      chemotherapy, and use of external beam radiation has been only described in few
      case reports. Given the sensitivity of pancreatic endocrine tumors to cytotoxic
      agents including streptozocin, doxorubicin and 5-FU, we have hypothesized that
      the combination of concurrent and sequential chemotherapy and radiation will
      yield higher response rates than acheivable with chemotherapy alone. METHODS: Six
      patients with locally advanced pancreatic endocrine tumors were treated with a
      protocol consisting of radiation concurrent with infusional 5-FU (or
      capecitabine) along with induction and consolidation chemotherapy (streptozocin
      and doxorubicin). We retrospectively determined the objective radiographic
      response rate. RESULTS: The objective response rate was 80%. With a median follow
      up of 29 months, all six patients in the study have had continued reduction in
      tumor size from the time of the first posttreatment scan to the most recent scan.
      None of the patients have experienced local or metastatic disease progression.
      Treatment was well tolerated with minimal toxicity. CONCLUSION: The combination
      of concurrent and sequential chemoradiotherapy appears to be a highly effective
      treatment for locally advanced pancreatic endocrine tumors.

PMID- 17541258
TI  - Glucocorticoid resistance following herpes simplex-1 infection: role of
      hippocampal glucocorticoid receptors.
AB  - Herpes simplex-1 (HSV-1) is a sporadic cause of viral encephalitis. We have
      previously demonstrated that corneal HSV inoculation markedly activates the
      hypothalamo-pituitary-adrenal (HPA) axis. This activation depends on host derived
      brain interleukine-1 and was resistant to pretreatment with dexamethasone (dex),
      possibly because immune factors such as pro-inflammatory cytokines can modify the
      binding capacity of glucocorticoids in the hippocampus. In the present study, we
      examined whether resistance of the HPA axis activation following intracerebral
      HSV-1 infection to dex-induced suppression is associated with modifications in
      hippocampal or pituitary glucocorticoids (GC) receptors or GC receptors in
      cultured astrocytes. Male rats were injected intracerebroventricularly with
      purified HSV-1 or vehicle. 48 h later, dex or vehicle was injected
      intraperitoneally. Rats were sacrificed 3.5 h later. ACTH and corticosterone (CS)
      were measured in the serum. Specific binding of 3H-dex was measured in the
      cytosolic fraction of the hippocampus and the pituitary. Dex failed to reduce
      ACTH and CS responses to HSV-1 infection. In contrast, dex significantly reduced
      ACTH and CS responses to acoustic neural stimuli. Infection with HSV-1 markedly
      reduced the hippocampal maximal specific binding of dex with no effect on the
      dissociation constant (Kd) values. HSV-1 had no effect on the binding of dex in
      the pituitary. Infection of cultured astrocytes with HSV-1 also reduced the
      maximal specific binding of dex, but increased the Kd value. The results suggest
      that HSV-1 induced GC resistance may be mediated by downregulation of GC
      receptors in hippocampal tissue. These results may clarify a mechanism
      responsible for GC resistance following immune challenges.

PMID- 17541259
TI  - Effect of an increase in brain serotonin on the osmoregulatory response to a hypo
      or hyperosmotic load in Wistar and vasopressin-deficient Brattleboro rats.
AB  - Serotonin and its receptor agonists stimulate the release of arginine vasopressin
      (AVP) into peripheral blood under intraventricular injection. To test the
      hypothesis that brain serotonin can modulate the development of natural
      osmoregulatory responses, the effect of an increase in endogenous brain serotonin
      on the response to an intragastric hypo- or hyperosmotic loading was studied in
      Wistar and AVP-deficient Brattleboro rats. 5-Hydroxytryptophan (5-HTP), the rate
      limiting serotonin biosynthesis precursor known to increase the brain level of
      serotonin, was injected intraperitoneally (5 mg/100 g body weight). The renal
      functional parameters (glomerular filtration rate [GFR], free water reabsorption,
      and urine flow rate) were monitored during the 4 h after intragastric infusion of
      water or a 2% NaCl solution (5% of body weight). Plasma AVP was measured by
      radioimmunoassay. In Wistar rats, intraperitoneal injection of 5-HTP at the same
      time as water loading prevented the development of the renal diuretic response:
      there was no increase in urine flow rate and GFR, and free water reabsorption
      remained at the high level. In AVP-deficient Brattleboro rats, unlike Wistar
      rats, 5-HTP treatment was without effect on the renal function parameters. In
      Wistar rats, injection of 5-HTP at the peak of water diuresis produced an
      abrogation of the diuretic response to water loading due to the increase in free
      water reabsorption. Plasma AVP increased from 1.2 +/- 0.4 to 4.2 +/- 1.6 pg/ml (n
      = 8 in each group, p < 0.01). Hyperosmotic treatment of Wistar rats with a 2%
      NaCl solution stimulated AVP secretion compared to baseline (from 3.2 +/- 0.1, n
      = 7 to 5.6 +/- 0.9, n = 7, p < 0.01), and the saluretic response developed on the
      background of high free water reabsorption. When injected concomitantly with NaCl
      solution, 5-HTP revealed no additive effect on plasma AVP and on free water
      reabsorption. We conclude that the 5-HTP-caused increase in brain serotonin
      contributed significantly to the dynamics of changes in the osmoregulatory
      response to the hypo-osmotic challenge due to stimulation of AVP secretion. 5-HTP
      had no additive effect on the osmoregulatory response to hyperosmotic loading.
      Peripherally injected 5-HTP had no effect on the renal function, being absent in
      AVP-deficient Brattleboro rats.

PMID- 17541260
TI  - Proliferative activity, apoptosis, and histogenesis in the early stages of rat
      tooth extraction wound healing.
AB  - We examined the proliferative activity, apoptosis, and histogenesis in the early
      stages of the rat healing socket from just after extraction until new bone
      formation occurs. Thirty 11-week-old male Wistar rats underwent bilateral
      maxillary first molar tooth extraction. Five craniomaxillary tissue specimens
      were dissected at the following time points: at 12 h, days 1, 3, 5, 7 and 10
      after surgery. The immunohistochemical expression of both proliferating cell
      nuclear antigen (PCNA) and the Ki67 counterpart of rodent (MIB5) for
      proliferative activity and both the TUNEL reaction and the immunohistochemical
      expression of single-strand DNA for apoptosis were evaluated using 6-mum-thick
      serial paraffin sections, which were prepared in the coronal plane. The positive
      cell counts in the socket were converted into the cell numbers per mm(2) as
      either the proliferative index (PI) or the apoptotic index (AI). The PI and the
      AI showed maximum levels at 5 days and 12 h after extraction, respectively. The
      proliferative activity in the early stages of extraction wound healing is
      initially distributed in the remaining periodontium with load-induced apoptosis,
      next in the proliferative fibrous tissue, and then around the trabeculae of the
      new bone marking its peak.

PMID- 17541261
TI  - Bronchoscopic measurement of collateral ventilation in a sheep model of
      emphysema.
AB  - BACKGROUND: The development of bronchoscopic therapies for emphysema has renewed
      interest in collateral ventilation. The success or failure of bronchoscopically
      placed valves or biologic glues may be determined by collateral ventilation,
      which is exaggerated in emphysema. Furthermore, the validity of various animal
      models of emphysema for testing such techniques must be understood in the context
      of their species-specific collateral ventilation. OBJECTIVES: To quantify
      collateral ventilation in a sheep model of emphysema using a simple in vivo
      bronchoscopic method. METHODS: Collateral ventilation was measured in 8
      anesthetized sheep using a simple method which measured pressure and flow through
      the working channel of a bronchoscope wedged in a segmental lung orifice. Animals
      then underwent nebulized papain treatments to generate emphysema, followed by
      repeat bronchoscopic measurements. RESULTS: There was a 33% decrease in
      resistance to collateral ventilation following papain treatment. Changes in
      collateral resistance were closely correlated with disease severity as measured
      by changes in segmental compliance, which increased 267%. CONCLUSIONS: Collateral
      ventilation is significantly increased in sheep following nebulized papain.
      Bronchoscopic measurement of collateral ventilation may be useful for evaluating
      other animal models of emphysema and for predicting the response to bronchoscopic
      therapies in human emphysema patients.

PMID- 17541262
TI  - Titration efficacy of two auto-adjustable continuous positive airway pressure
      devices using different flow limitation-based algorithms.
AB  - BACKGROUND: Auto-adjustable continuous positive airway pressure devices are
      widely used in titration procedures to determine therapeutic pressure levels in
      obstructive sleep apnea patients. However, differences in operational
      characteristics may influence the effect on the apnea-hypopnea index (AHI).
      OBJECTIVES: We compared the titration performance of two devices based on
      detection of inspiratory flow limitation, i.e. the Respironics REMstar Auto (RR)
      and the ResMed Spirit (RS). METHODS: Fifty obstructive sleep apnea patients were
      recruited for a double-blind randomized crossover trial. Both devices were
      employed overnight by means of split-night polysomnography. The primary outcome
      was the AHI. Secondary outcome measures were the snoring index, pressure profiles
      and subjective appraisal of sleep quality assessed the morning after the sleep
      study. The Wilcoxon signed rank test for matched pairs was applied to assess
      differences between treatment conditions. RESULTS: No significant differences
      were found in sleep parameters, subjective sleep quality and snoring index. The
      use of the RR was associated with a significantly lower AHI in comparison with
      the RS [mean (SD) 6.9 (11.6)/h vs. 9.4 (9.2)/h, p = 0.004]. This result was
      obtained at significantly lower pressure levels [P95 9.2 (2.3) cm H(2)O vs. 10.2
      (1.5) cm H(2)O, p = 0.001]. CONCLUSION: While the RR provided a lower AHI than
      the RS at lower pressure levels, it could not be assessed whether this difference
      was relevant for clinical outcomes. However, this face-to-face comparison of Auto
      adjustable continuous positive airway pressure devices seems useful for the
      assessment of titration efficacy.

PMID- 17541263
TI  - Cigarette smoking and incident chronic kidney disease: a systematic review.
AB  - BACKGROUND: Several studies have examined the role of cigarette smoking in the
      development of renal disease in human populations. However, there have been no
      systematic reviews on the evidence linking smoking with incident renal disease.
      METHODS: We performed an evidence-based evaluation of peer-reviewed research
      published during 1966-2005, from a search of five databases, including Ovid
      MEDLINE and EMBASE. RESULTS: Of the 28 studies that were reviewed, 11 were
      excluded from the final analysis due to poor methodological quality (n = 6), no
      reported risk estimate for the association between smoking and kidney disease (n
      = 3), inability to find a Japanese translator (n = 1), and duplicate cohort (n =
      1). Seventeen studies were included in the final analysis; seven studies found an
      overall significant association between smoking and incident chronic kidney
      disease, and three studies found a significantly increased risk of chronic kidney
      disease in current smokers that was gender and/or dose related. An increased risk
      of developing chronic kidney disease among smokers was significantly associated
      with male gender (relative risk 2.4, 95% confidence interval 1.2-4.5), >20
      cigarettes smoked/day (odds ratio 1.51, 95% confidence interval 1.06-2.15, and
      relative risk 2.3, 95% confidence interval 1.2-4.3), and smoking >40 years (odds
      ratio 1.45, 95% confidence interval 1.00-2.09). A pooled estimate of the relative
      risk (meta-analysis) was deemed inappropriate due to the heterogeneity in
      methodologies utilized by the different studies. CONCLUSIONS: This comprehensive
      review reveals overall evidence for current cigarette smoking as a risk factor
      for incident chronic kidney disease. Further investigation is needed to more
      carefully examine the strength of the association between cigarette smoking and
      incident kidney disease.

PMID- 17541264
TI  - The prevalence of resistant bacterial colonization in chronic hemodialysis
      patients.
AB  - BACKGROUND: Hospitalized dialysis patients are at increased risk for colonization
      and infection with resistant bacterial strains. METHODS: We performed a cross
      sectional analysis of the prevalence of methicillin-resistant Staphylococcus
      aureus (MRSA) and vancomycin-resistant Enterococcus (VRE) colonization in 198
      hemodialysis outpatients, 75 of whom had longitudinal screening data from prior
      hospitalization. Nasal specimens for MRSA, perirectal specimens for VRE, and
      permanent catheter exit site specimens were collected. RESULTS: MRSA colonization
      was present in 5.6% and VRE colonization in 3.14%. Univariate analyses revealed
      that prior exposure (defined as infection/colonization) with MRSA,
      hospitalization, and low serum albumin were associated with MRSA colonization.
      VRE colonization was associated with hospitalization, prior VRE or MRSA exposure,
      low serum albumin, and low ferritin. Multivariate analyses revealed MRSA
      colonization was predicted by prior MRSA exposure and VRE colonization was
      predicted by prior VRE exposure and number of hospitalizations. Among the 75
      participants with longitudinal screening data, MRSA colonization was associated
      with prior MRSA history, and VRE colonization was associated with prior MRSA or
      VRE. CONCLUSIONS: Generally low rates of MRSA and VRE colonization were observed
      in hemodialysis outpatients. Prior hospital screening was predictive of future
      outpatient colonization and may be useful in risk assessment.

PMID- 17541265
TI  - Changes in plasma amino Acid levels do not predict satiety and weight loss on
      diets with modified macronutrient composition.
AB  - OBJECTIVE: Serotonin mediates satiety in the central nervous system. Brain
      serotonin content depends on the plasma ratio of tryptophan (Trp) to large
      neutral amino acids (LNAA) and may be affected by diet composition. We examined
      whether high-carbohydrate or high-protein diets induce satiety and weight loss by
      altering plasma concentrations of these amino acids. METHODS: In study 1 (n = 16,
      BMI = 27.0 +/- 2.3), we compared plasma Trp and LNAA concentrations averaged over
      24 h after 2 weeks of consuming isocaloric diets containing either 45 or 65% of
      total energy as carbohydrate. In study 2 (n = 19, BMI = 26.2 +/- 2.1), we made
      the same measurements following diets containing either 15 or 30% of total energy
      as protein. To assess satiety in both studies, we recorded caloric intake and
      weight changes during a subsequent 12-week period of ad libitum consumption of
      the experimental diets. RESULTS: Ad libitum caloric intake fell by 222 +/- 81
      kcal/day with a 3.7 +/- 0.6 kg weight loss at 12 weeks in study 1. Ad libitum
      caloric intake fell by 441 +/- 63 kcal/ day with a 4.9 +/- 0.5 kg weight loss at
      12 weeks in study 2. The 24-hour averaged plasma concentration of Trp and the
      Trp:LNAA ratio were unaffected by the isocaloric increase in carbohydrate or
      protein consumption that preceded the ad libitum administration of the 2 diets.
      CONCLUSION: An increase in either carbohydrate or protein intake increases
      satiety and leads to significant weight loss, however, these effects are not
      mediated by an increase in plasma concentration of Trp or the Trp:LNAA ratio.

PMID- 17541266
TI  - Effect of zinc supplementation on thyroid hormone function. A case study of two
      college females.
AB  - BACKGROUND/AIMS: Zinc is crucial for proper thyroid hormone metabolism; zinc
      deficiency may result in decreased thyroid hormone levels and resting metabolic
      rate (RMR). The purpose of this investigation was to assess the effects of zinc
      supplementation on plasma zinc, serum ferritin, plasma total triiodothyronine
      (T(3)) and thyroxine (T(4)), serum free T(3) and T(4), and thyroid-stimulating
      hormone concentrations, and RMR in zinc-deficient, physically active women.
      METHODS: Two zinc-deficient female college students (ZD1 and ZD2) were
      supplemented with 26.4 mg/day of zinc (as zinc gluconate), and the above
      parameters were analyzed at 0, 2 and 4 months. RESULTS: Zinc deficiency was
      clinically corrected in both subjects, while serum ferritin concentration
      declined to classify both subjects as borderline iron deficient (ZD1 = 15.3 and
      ZD2 = 15.3 ng/ml at 4 months). At 4 months, total T(3) concentrations increased
      in ZD1, while all thyroid hormone concentrations increased in ZD2. RMR increased
      in both subjects by 4 months. CONCLUSION: Zinc supplementation appeared to be
      directly responsible for the increase in plasma zinc and decline in serum
      ferritin concentrations in both subjects. Zinc supplementation appeared to have a
      favorable effect on thyroid hormone levels, particularly total T(3), and RMR.

PMID- 17541267
TI  - Three successive cases of enteric anisakiasis.
AB  - Enteric anisakiasis is relatively rare, and the preoperative diagnosis is
      difficult. We report 3 cases of enteric anisakiasis: 1 was confirmed by
      operation, and the other 2 cases were suspected by the patient history. The 1st
      patient was a 48-year-old female presenting with abdominal pain. An abdominal
      computed tomography scan showed a dilated small intestine and accumulation of
      ascites. We performed partial resection of the small intestine, and an Anisakis
      nematode was found on the wall of the resected bowel. After surgery, the detailed
      history revealed that the patient consumed a raw sardine with vinegar and miso,
      fermented soybean paste. Three days after her operation, 2 men presenting with
      abdominal pain visited the hospital, and computed tomography scans of the
      patients showed dilated small intestines and accumulation of ascites. By taking
      patient histories, we found that both of them consumed sardines with vinegar and
      miso, and both were given conservative treatment with fasting and transfusion. By
      the experience of the 1st case, we could diagnose the following 2 cases as having
      enteric anisakiasis. In conclusion, the possibility of anisakiasis should be
      considered in patients with abdominal pain after ingesting raw fish, especially
      when intestinal obstruction is suspected.

PMID- 17541268
TI  - Inflammatory fibroid polyp or Vanek's tumour.
AB  - We report a case of a 65-year-old woman who presented with recurrent episodes of
      severe, postprandial abdominal pain followed by projectile vomiting. Gastroscopy
      revealed a large polyp in the prepyloric region. During peristalsis, the polyp
      was repeatedly 'passing' through the pylorus into the duodenal bulb, hence
      obstructing the lumen. The polyp was eventually removed in a piecemeal fashion.
      Histopathologic examination revealed an inflammatory fibroid polyp (known also as
      Vanek's tumour). A brief review on inflammatory fibroid polyps follows.

PMID- 17541270
TI  - Recent advances in eosinophil biology.
AB  - Eosinophils are pleiotropic multi-functional leukocytes involved in initiation
      and propagation of diverse inflammatory responses. Recent studies examining
      eosinophil biology have focused on delineating the molecular basis of
      FIP1L1/PDGRFalpha-fusion gene induced HES, the molecular steps involved in
      eosinophil recruitment in tumor-associated eosinophilia and EGID, and the role of
      eosinophils in asthma. In this review, these studies are summarized, focusing on
      the implications of these findings in the understanding the role of eosinophils
      in diseases.

PMID- 17541271
TI  - Anti- and proinflammatory effects of 15-deoxy-delta-prostaglandin J2(15d-PGJ2) on
      human eosinophil functions.
AB  - The cyclopentenone prostaglandin 15-deoxy-Delta(12,14)-prostaglandin J(2) (15d
      PGJ(2)) is recognized as a potent lipid mediator that is derived from PGD(2),
      which is produced abundantly in allergic inflammatory sites. It is now
      established that 15d-PGJ(2) negatively regulates cellular functions through its
      intracellular targets such as peroxisome proliferator-activated receptor-gamma
      (PPARgamma). However, recent studies revealed that 15d-PGJ(2) appears to possess
      not only anti-inflammatory activities but also a proinflammatory potential
      depending on its concentration and the activation state of the target cell. For
      instance, at low concentrations, 15d-PGJ(2) enhances eotaxin-induced chemotaxis,
      shape change, and actin reorganization in eosinophils through its ligation with
      PPARgamma. Moreover, 15d-PGJ(2) itself is a potent chemoattractant, and it
      induces calcium mobilization, and up-regulates CD11b expression through its
      membrane receptor--chemoattractant receptor-homologous molecule expressed on Th2
      cells (CRTH2). Conversely, at high concentrations, 15d-PGJ(2) inhibits eosinophil
      survival by inducing apoptosis in a PPARgamma-independent manner. Here, we
      discuss the pathophysiological roles of 15d-PGJ(2) that could act as a paracrine,
      autocrine, and intracrine substance to regulate eosinophil functions.

PMID- 17541272
TI  - Possible novel receptor for PGD2 on human bronchial epithelial cells.
AB  - Prostaglandin D(2) (PGD(2)), a major prostanoid produced by activated mast cells,
      has long been implicated in allergic diseases. Recent studies have shown that
      PGD(2) exerts its effects through two different G-protein-coupled receptors
      (GPCRs), the D-prostanoid receptor (DP) and the chemoattractant receptor
      homologous molecule expressed on T helper type-2 cells (CRTH2), expressed in
      various human tissues. The PGD(2)/CRTH2 system mediates the chemotaxis of
      eosinophils, basophils, and Th2 cells, which are involved in the induction of
      allergic inflammation. We have reported that normal human bronchial epithelial
      cells (NHBE) and epithelial cell lines (NCI-H(292)) expressed CRTH2, and PGD(2)
      induces production of IL-8 and GM-CSF. This review discusses the role of CRTH2/DP
      on epithelial cells and mentions a possible novel receptor for PGD(2).

PMID- 17541273
TI  - Mechanism for the differentiation of EoL-1 cells into eosinophils by histone
      deacetylase inhibitors.
AB  - BACKGROUND: EoL-1 cells have a FIP1L1-PDGFRA fusion gene which causes the
      transformation of eosinophilic precursor cells into leukemia cells. Recently, we
      suggested that the induction of differentiation of EoL-1 cells into eosinophils
      by the HDAC inhibitors apicidin and n-butyrate is due to the continuous
      inhibition of HDACs. However, neither apicidin nor n-butyrate inhibited the
      expression of FIP1L1-PDGFRA mRNA, although both these inhibitors suppressed cell
      proliferation. Therefore, in this study, we analyzed whether the levels of FIP1L1
      PDGFRalpha protein and phosphorylated-Stat5 involved in the signaling for the
      proliferation of EoL-1 cells are attenuated by HDAC inhibitors. METHODS: EoL-1
      cells were incubated in the presence of apicidin, TSA or n-butyrate. FIP1L1
      PDGFRalpha and phosphorylated-Stat5 were detected by Western blotting. RESULTS:
      Treatment of EoL-1 cells with apicidin at 100 nM or n-butyrate at 500 microM
      decreased the levels of FIP1L1-PDGFRalpha protein and phosphorylated-Stat5, while
      that with trichostatin A at 30 nM did not. CONCLUSIONS: The decrease in the level
      of FIP1L1-PDGFRalpha protein caused by apicidin and n-butyrate might be one of
      the mechanisms by which EoL-1 cells are induced to differentiate into eosinophils
      by these HDAC inhibitors.

PMID- 17541274
TI  - Effect of interleukin-13 or tumor necrosis factor-alpha on eosinophil adhesion to
      endothelial cells under physiological flow conditions.
AB  - RATIONALE: We examined the mechanisms used by eosinophils to accumulate on IL-13-
      or TNF-alpha-stimulated human umbilical vein endothelial cells (HUVECs) under
      flow conditions. METHODS: HUVECs were treated for 1, 3, 6, 18 and 24 h with IL-13
      or TNF-alpha (1-100 ng/ml). Human eosinophils were infused at physiologic flow
      rates (0.5 dyn/cm(2)) for 10 min, and attached eosinophils were counted. RESULTS:
      Under these flow conditions, eosinophils accumulated efficiently on IL-13
      stimulated (109 +/- 18 cells/field) or TNF-alpha-stimulated (96 +/- 27
      cells/field) HUVECs in a concentration-dependent manner. Eosinophil accumulation
      on IL-13-activated HUVECs was first observed at 3 h and reached a maximum at 24
      h. On the other hand, the levels of eosinophils accumulating on TNF-alpha
      activated HUVECs were the same at all time points (1, 3, 6, 18 and 24 h). Anti
      alpha4 integrin mAb inhibited eosinophil accumulation on both IL-13- and TNF
      alpha-activated HUVECs. CONCLUSIONS: Eosinophil accumulation on HUVECs under
      physiologic flow conditions is differentially regulated by IL-13 and TNF-alpha.

PMID- 17541275
TI  - Eosinophils do not enhance the trans-basement-membrane migration of neutrophils.
AB  - BACKGROUND: There is increasing evidence that both neutrophilic and eosinophilic
      inflammation persist in the airways of patients with severe asthma. We have
      reported a positive relationship between the concentrations of eosinophils and
      neutrophils in sputum from severe asthmatics, suggesting a possible role of
      eosinophils in regulating neutrophilic inflammation. The aim of this study was to
      investigate whether activated eosinophils modify the trans-basement membrane
      migration (TBM) of neutrophils. METHODS: Eosinophils and neutrophils were
      isolated from peripheral blood drawn from healthy donors. The TBM of neutrophils
      in response to a variety of chemoattractants was evaluated in the presence or
      absence of eosinophils by using the chambers with a Matrigel-coated Transwell
      insert. RESULTS: As expected, eotaxin (10 nM) and RANTES (10 nM), but not IL-8
      (10 nM), induced the TBM of eosinophils. On the contrary, only IL-8 induced the
      TBM of neutrophils. When eosinophils were coincubated with neutrophils and
      stimulated with IL-8, the TBM of eosinophils was significantly augmented. On the
      other hand, when neutrophils were coincubated with eosinophils and stimulated
      with eotaxin or RANTES, the TBM of neutrophils was not modified. CONCLUSIONS:
      Neutrophils migrated by IL-8 may lead eosinophils to accumulate in the airways of
      patients with severe asthma. On the other hand, it is unlikely that eosinophils
      migrated by chemoattractants such as CC chemokines regulate neutrophilic
      inflammation.

PMID- 17541276
TI  - Theophylline attenuates the neutrophil-dependent augmentation of eosinophil trans
      basement membrane migration.
AB  - BACKGROUND: Recent evidence suggests that both neutrophilic and eosinophilic
      inflammation persist in the airways of patients with severe asthma. Neutrophils
      can secrete a variety of mediators which may augment the migration of
      eosinophils. We have reported that activated neutrophils augment the trans
      basement membrane migration (TBM) of eosinophils in vitro. Theophylline has been
      shown to modulate some functions of both neutrophils and eosinophils. The
      objective of this study was to evaluate whether theophylline modulates the
      neutrophil-dependent augmentation of eosinophil TBM. METHODS: Eosinophils and
      neutrophils were isolated from peripheral blood collected from healthy donors and
      were then preincubated with either 0.1 mM theophylline or the medium control. The
      TBM of eosinophils in response to IL-8 was evaluated in the presence or absence
      of neutrophils by using the chambers with a Matrigel-coated Transwell insert. The
      generation of O(2)(-) was evaluated by the cytochrome c reduction assay. RESULTS:
      As previously reported, IL-8-stimulated neutrophils significantly augmented the
      TBM of eosinophils. Theophylline significantly attenuated the neutrophil
      dependent augmentation of eosinophil TBM (p < 0.001) and did not directly modify
      the TBM of neutrophils in response to IL-8 or LTB4. Similarly, the LTB4-induced
      TBM of eosinophils was not modified by theophylline. Finally, theophylline
      attenuated the superoxide anion generation from IL-8-stimulated neutrophils on
      the Matrigel-coated plates. CONCLUSIONS: Our results show that theophylline can
      attenuate the neutrophil-dependent augmentation of eosinophil TBM. This effect is
      possibly attributable to the suppression of neutrophil activation provoked by the
      combination of basement membrane and IL-8.

PMID- 17541277
TI  - B and T lymphocyte attenuator inhibits antigen-induced eosinophil recruitment
      into the airways.
AB  - BACKGROUND: Signaling through CD28 family co-receptors regulates activation of
      CD4(+) T cells positively and negatively. It has been shown that stimulatory co
      receptors such as CD28 and ICOS play critical roles in the induction of allergic
      airway inflammation. However, the role of B and T lymphocyte attenuator (BTLA),
      an inhibitory co-receptor expressed preferentially in Th1 cells, in the
      regulation of allergic airway inflammation remains to be determined. METHODS: We
      examined antigen-induced eosinophil recruitment and cytokine production in the
      airways in antigen-sensitized BTLA-deficient (BTLA-/-) mice. We also examined
      antigen-induced cytokine production and cell proliferation of splenic T cells in
      antigen-sensitized BTLA-/- mice. RESULTS: Antigen-induced eosinophil recruitment
      and IL-5 production in the airways was enhanced in antigen-sensitized BTLA-/-
      mice. On the other hand, antigen-induced Th1 and Th2 cytokine production as well
      as T cell proliferation of splenocytes was normal in BTLA-/-mice. CONCLUSION:
      BTLA inhibits antigen-induced eosinophil recruitment into the airways by
      preventing IL-5 production from Th2 cells.

PMID- 17541278
TI  - IgE- and FcepsilonRI-mediated enhancement of surface CD69 expression in
      basophils: role of low-level stimulation.
AB  - Surface-expressed CD69 is a recently recognized activation marker for basophils
      and is reported to be strongly induced in vitro by IL-3. In this study, we
      investigated whether IgE- and high-affinity receptor for IgE (FcepsilonRI)
      dependent stimuli can affect basophil CD69 expression. Highly purified basophils
      were cultured for 24 h in the presence of anti-FcepsilonRI alpha-chain mAb, CRA-1
      and IL-3, and surface CD69 expression was analyzed by flow cytometry. CRA-1 mAb
      at 1 ng/ml or lower concentrations, levels too low to provoke direct histamine
      release, dose-dependently enhanced surface CD69 expression in the presence of IL
      3, although low-dose CRA-1 mAb failed to induce CD69 expression in the absence of
      IL-3. Recombinant Der f 2 at 10 to 100 pg/ml enhanced CD69 levels in the presence
      of IL-3 in basophils from mite-sensitive subjects. These results suggest that
      allergens may influence basophil CD69 expression even when the levels of the
      antigens are too low to trigger direct degranulation. Upregulated CD69 expression
      on locally accumulated basophils in bronchial asthma may be attributed at least
      in part to a combination of local cytokines, especially IL-3, plus exposure to
      low levels of IgE-crosslinking allergens.

PMID- 17541279
TI  - Rapid and strong induction of apoptosis in human eosinophils by anti-CD30 mAb
      coated microspheres and phagocytosis by macrophages.
AB  - BACKGROUND: Eosinophils represent a potential therapeutic target in allergic
      diseases. We previously reported that two clones of anti-CD30 mAbs (HRS-4 and Ber
      H8) induced extremely rapid and intense apoptosis in human eosinophils in vitro,
      but only when the mAbs were immobilized on plates [Matsumoto K, J Immunol
      2004;172:2186]. As the initial step towards clinical application of these anti
      CD30 mAbs in the treatment of allergic diseases, we made an attempt to clarify
      two issues; first, whether or not anti-CD30 mAb-coated microspheres can
      efficiently induce apoptosis in human eosinophils, and second, whether or not
      these apoptotic eosinophils can be phagocytosed by macrophages without the
      release of granular proteins. METHODS: Purified human eosinophils were treated
      with anti-CD30 mAb-coated polystyrene microspheres (diameter, 1.44 mum).
      Apoptosis was determined by annexin V-binding. For the phagocytosis assay,
      eosinophils were co-cultured with monocyte-derived human macrophages or PMA
      pretreated U-937 cells. Phagocytosis was determined by light microscopy and by
      the eosinophil-derived neurotoxin (EDN) concentration in the supernatant.
      RESULTS: Anti-CD30 mAb-coated, but not control IgG1-coated microspheres
      significantly reduced eosinophil survival in a dose-dependent manner. Marked
      phagocytosis of the apoptotic eosinophils by macrophages was also observed when
      the eosinophils were treated with anti-CD30 mAb-coated microspheres. The
      apoptotic eosinophils released large amounts of EDN in the absence of
      macrophages; however, the EDN levels were significantly decreased when the
      eosinophils were co-cultured with macrophages. CONCLUSIONS: Anti-CD30 mAb-coated
      microspheres are capable of inducing rapid and strong apoptosis in human
      eosinophils. Furthermore, the apoptotic eosinophils were also phagocytosed by
      macrophages with minimal release of the granular proteins.

PMID- 17541280
TI  - IL-4 gene transcription in human T cells is suppressed by T-bet.
AB  - T-bet is crucially implicated in Th1 differentiation due to its strong promoting
      activity for IFN-gamma gene transcription. However, the regulatory role of T-bet
      in Th2 cytokines is not fully delineated. METHODS: The effect of T-bet on mRNA
      expression as well as the promoter activity of IL-4 in human T cells was
      investigated by employing quantitative RT-PCR and fluorescence-based promoter
      reporter assay procedures. RESULTS: IL-4 mRNA expression as well as the
      transcriptional activity of 5'-flanking region in the IL-4 gene encompassing 
      1105 to +4 in Jurkat cells was clearly upregulated upon stimulation. The
      inducible mRNA expression and the promoter activity of IL-4 were significantly
      diminished by ectopic expression of T-bet. CONCLUSION: IL-4 gene transcription is
      inhibited by T-bet via the suppression of its promoter activity, independently of
      IFN-gamma. T-bet facilitates Th1 differentiation through not only upregulation of
      IFN-gamma, but also downregulation of IL-4 gene transcription.

PMID- 17541281
TI  - IL-2-induced IL-9 production by allergen-specific human helper T-cell clones.
AB  - BACKGROUND: IL-9 is an important cytokine in allergic diseases such as asthma,
      atopic dermatitis, etc. T helper (Th) cells seem to be the main source of IL-9.
      Cellular and molecular mechanisms of IL-9 production by human Th cells have been
      poorly understood. METHODS: Dermatophagoides farinae(Der f)-specific Th clones
      were established from peripheral blood lymphocytes of atopic asthmatics, and
      cytokine synthesis in response to various stimuli was determined by specific
      ELISAs. RESULTS: IL-9 was produced by 14 of 27 human Th clones upon T cell
      receptor (TCR) stimulation, immobilized anti-CD3 antibody (Ab). IL-9 production
      was significantly enhanced by the addition of anti-CD28 Ab into the culture,
      indicating the role of costimulatory signal on IL-9 synthesis. Pharmacologically,
      IL-9 production was induced by ionomycin (IOM) alone, and enhanced by phorbol 12
      myristate 13-acetate (PMA). rIL-2 induced IL-9 production by 8 out of 19 Th
      clones. IL-9 production by Th clones stimulated with immobilized anti-CD3 Ab was
      significantly suppressed by the addition of anti-IL-2 neutralizing Ab into the
      culture. CONCLUSION: Approximately half of the Der f-specific Th clones derived
      from atopic asthmatics produced IL-9 upon TCR stimulation. Ca(2+) signal, CD28
      signal, and IL-2 receptor signal seem to play important roles in IL-9 production
      by human Th cells. Moreover, synthesis of IL-9, a Th2 cytokine, is dependent on
      IL-2, a Th1 cytokine, which is produced by Th cells themselves.

PMID- 17541282
TI  - IL-9 production by peripheral blood mononuclear cells of atopic asthmatics.
AB  - BACKGROUND: IL-9 might play a critical role in pathogenesis and development of
      atopic asthma, but there are few reports on allergen-specific IL-9 production by
      peripheral blood mononuclear cells (PBMCs) obtained from adult asthmatics.
      METHODS: PBMCs were obtained from adult atopic asthmatics and incubated with
      Dermatophagoides farinae(Der f) extract for the designated time periods. The
      resulting supernatants were assayed for IL-9 by specific sandwich ELISA. RESULTS:
      IL-9 production was detectable on day 2 and reached maximum on day 6 after
      stimulation of PBMCs with Der f extract. IL-9 production in response to Der f
      extract increased in a dose-dependent manner. CD2- or CD4-bearing cell depletion
      completely abolished IL-9 production by PBMCs, while CD8-bearing cell depletion
      did not affect it. CONCLUSION: CD4+ lymphocytes are the principal source of IL-9
      produced by PBMCs of adult atopic asthmatics.

PMID- 17541283
TI  - Role of RIG-I, MDA-5, and PKR on the expression of inflammatory chemokines
      induced by synthetic dsRNA in airway epithelial cells.
AB  - BACKGROUND: We hypothesized that synthetic double-stranded (ds)RNA may mimic
      viral infection and reported that dsRNA stimulates expression of inflammatory
      chemokines through a receptor of dsRNA Toll-like receptor (TLR) 3 in airway
      epithelial cells. In this study, we focused our study on the role of other
      receptors for dsRNA, such as retinoic acid-inducible gene I (RIG-I), melanoma
      differentiation-associated gene 5 (MDA-5), and double-stranded RNA-dependent
      protein kinase (PKR). METHODS: Airway epithelial cell BEAS-2B was cultured in
      vitro. Expression of target RNA and protein were analyzed by PCR and ELISA. To
      analyze the role of receptors for dsRNA, knockdown of theses genes was performed
      with short interfering RNA (siRNA). RESULTS: We first investigated the effects of
      chloroquine, an inhibitor of lysosomal acidification, on the expression of
      chemokines. Preincubation with 100 microM chloroquine significantly inhibited the
      expression of mRNA for RANTES, IP-10, and IL-8, stimulated by poly I:C,
      indicating that poly I:C may react with a receptor expressed inside the cells.
      RIG-I, MDA-5, and PKR are supposed to be expressed inside the airway epithelial
      cells. However, the expression of chemokines stimulated with poly I:C was not
      significantly inhibited for these putative receptors in the cells which were
      transfected with siRNA. CONCLUSIONS: Synthetic dsRNA poly I:C stimulates the
      expression of inflammatory chemokines in airway epithelial cells, but the
      putative receptors for dsRNA such as RIG-I, MDA-5, or PKR may not play pivotal
      roles in this process. TLR3 may play a major role as reported previously.

PMID- 17541285
TI  - Expression of interleukin-17F in a mouse model of allergic asthma.
AB  - BACKGROUND: Interleukin (IL)-17F is a recently discovered cytokine and is derived
      from a panel of limited cell types, such as activated CD4+ T cells, basophils,
      and mast cells. IL-17F is known to induce several cytokines and chemokines.
      However, its involvement in airway inflammation has not been well understood. To
      this end, the expression of IL-17F and the inhibitory effects of glucocorticoids
      on its expression in a mouse model of asthma were examined. METHODS: Five-week
      old BALB/c male mice were sensitized by intraperitoneal injection (i.p.) of
      ovalbumin (OVA) with alum, and challenged by daily inhalation of aerosolized 1%
      OVA. 24 h after last challenge (OVA/OVA), the expression of IL-17F was examined
      in lung tissues by immunohistochemistry and reverse-transcription polymerase
      chain reaction. Control mice were sensitized and challenged with saline
      (Sham/Sham). In addition, a group OF OVA-sensitized mice received i.p. injection
      of water-soluble dexamethasone (DEX) in saline 1 h before ova challenge
      (OVA/DEX). RESULTS: In sham-challenged mice, IL-17F was not expressed in the
      lungs, while, in contrast, IL-17F was predominantly expressed in bronchial
      epithelial cells in addition to the infiltrating inflammatory cells in OVA/OVA
      mice. Further, the expression of IL-17 F was significantly attenuated by the
      treatment of mice with DEX. CONCLUSION: These results suggest that bronchial
      epithelium-derived IL-17F may represent a new pharmacological target for
      glucocorticoids and may play a role in allergic asthma.

PMID- 17541284
TI  - Differential regulation of chemokine expression by Th1 and Th2 cytokines and
      mechanisms of eotaxin/CCL-11 expression in human airway smooth muscle cells.
AB  - BACKGROUND: Airway smooth muscle (ASM) cells may contribute to the pathogenesis
      of asthma including airway inflammation and remodeling. We focused our study on
      the regulation of chemokine expression by cytokines and analyzed the mechanisms
      of eotaxin/CCL-11 expression in ASM cells. METHODS: Human ASM cells were cultured
      in vitro and treated with IL-4, interferon-gamma (IFNgamma), and tumor necrosis
      factor-alpha (TNFalpha). Secretion of chemokines into the culture medium was
      analyzed by ELISA. Expression of eotaxin mRNA was analyzed by reverse
      transcription-polymerase chain reaction (RT-PCR). Binding of transcription factor
      signal transducer activator of transcription (STAT) 6 to the eotaxin promoter
      derived DNA was analyzed by pull-down Western blot. To assess transcriptional
      regulation of eotaxin, cells were transfected with eotaxin promoter-luciferase
      reporter plasmids, and activity was determined by dual luciferase assay. RESULTS:
      The Th2 cytokine IL-4 preferentially stimulated the expression of the CC
      chemokine receptor (CCR) 3-ligand chemokines eotaxin, eotaxin-3, and MCP-4. The
      Th1 cytokine IFNgamma stimulated the expression of chemokines IP-10 and RANTES.
      IL-4 stimulated nuclear translocation of signal transducer activator of
      transcription 6 (STAT6) and its binding to the eotaxin promoter region. IL-4
      activated the eotaxin promoter and its activity was inhibited by mutation of the
      binding site for STAT6 in the promoter. CONCLUSIONS: The Th2 cytokine IL-4
      preferentially stimulated the expression of CCR3 ligand chemokines including
      eotaxin in ASM cells. The transcription factor STAT6 may play a pivotal role in
      the activation of eotaxin transcription in response to IL-4.

PMID- 17541286
TI  - Involvement of galectin-9 in guinea pig allergic airway inflammation.
AB  - BACKGROUND: There is little information about the involvement of galectin-9 (Gal
      9) in allergic inflammation. Thus, we investigated the role of Gal-9 in asthma
      model guinea pigs. METHODS: Airway resistance (R(aw)) was measured using a double
      flow plethysmograph system. Gal-9 expression in the lung was assessed by Western
      blot and immunohistochemistry. Eosinophil chemotactic activity was evaluated in a
      chamber containing a polyvinylpyrolidone-free membrane. Cell apoptosis was
      analyzed on a flowcytometry with propidium iodide. RESULTS: In cloning guinea pig
      Gal-9 we identified three isoforms that differ only in the length of their linker
      peptides, just as with human Gal-9. Guinea pig Gal-9 was found to be a
      chemoattractant for eosinophils and to promote induction of apoptosis in
      sensitized but not non-sensitized T lymphocytes. In allergic airway
      hypersensitivity model, a low level of Gal-9 expression was observed in the
      nonsensitized/nonchallenged group, but upregulation was detected at 7 h after
      challenge and sustained up to 24 h. Such upregulation correlated with elevation
      of eosinophil peroxidase activity but not with increased R(aw). CONCLUSIONS: The
      present results provide evidence that Gal-9 is not involved in airway
      hypersensitivity, but is partly involved in prolonged eosinophil accumulation in
      the lung.

PMID- 17541287
TI  - Effect of formoterol on allergen-induced cytokine synthesis by atopic asthmatics.
AB  - BACKGROUND: Effect of formoterol, long-acting beta(2 )agonists, on T cell
      cytokine synthesis was examined. METHODS: Human peripheral blood mononuclear
      cells were obtained from atopic asthmatics, and stimulated with
      Dermatophagoidesfarinae extract. Various concentrations of formoterol were added
      from the start of some cultures. Cytokine production and cell proliferation were
      analyzed. RESULTS: Allergen-induced IL-5, IL-13, and IFN-gamma production of PBMC
      were significantly suppressed by formoterol in a dose-dependent manner, whereas
      the proliferation response was not suppressed. CONCLUSION: Formoterol
      downregulates T cell functions of atopic asthmatics in vitro.

PMID- 17541288
TI  - T cells survey the stability of the self: a testable hypothesis on the
      homeostatic role of TCR-MHC interactions.
AB  - In the lifetime of an individual, every single gene will have undergone mutation
      on about 10(10) separate occasions. Nevertheless, cancer occurs mainly with
      advancing age. Here, we hypothesize that the evolutionary pressure driving the
      creation of the T cell receptor (TCR) repertoire was primarily the homeostatic
      surveillance of the genome. The subtly variable T cells may in fact constitute an
      evolutionary link between the invariable innate and hypervariable B cell systems.
      The new model is based on the homeostatic role of T cells, suggesting that
      molecular complementarity between the positively selected TCR and the self
      peptide-presenting major histocompatibility complex molecules establishes and
      regulates homeostasis, strictly limiting variations of its components.
      Notwithstanding, the 'homeostatic role of T cells' model offers a more realistic
      explanation as to how a naive clonal immune system can cope with the much faster
      replicating pathogens, despite a limited repertoire that is capable of facing
      only a small fraction of the vast antigenic universe at a time.

PMID- 17541289
TI  - Biomarkers of cardiovascular damage.
AB  - Acute coronary syndromes (ACS) are due to the rupture or erosion of atheromatous
      plaques. This produces, depending on plaque size, vascular anatomy and degree of
      collateral circulation, progressive tissue ischaemia which may progress to
      cardiomyocyte necrosis. This may then result in cardiac remodelling. Serum
      biomarkers are available which can be used for diagnosis of all of these stages.
      Markers to detect myocardial ischaemia at the pre-infarction stage are
      potentially the most interesting but also the most challenging. An ischaemia
      marker offers the opportunity to intervene to prevent progression to infarction.
      The problems with potential ischaemia markers are specificity and the reference
      diagnostic standard against which they can be judged. To date, only one,
      ischaemia-modified albumin(R), has reached the point where clinical studies can
      be performed. The measurement of the cardiac troponins, cardiac troponin T and
      cardiac troponin I, have become recognised as the diagnostic reference standard
      for myocardial necrosis. The sensitive nature of these tests has also revealed
      that myocardial necrosis is also found in a range of other clinical situations,
      highlighting the need to use all clinical information for diagnosis of acute
      myocardial infarction. The measurement of B-type natriuretic peptides can be
      shown to be diagnostic and prognostic in both ACS and detecting the sequelae of
      post-infarction myocardial insufficiency. The role of the B-type natriuretic
      peptides in detection of cardiac failure, both acute and chronic, is well defined
      but remains the subject of further studies, in ACS.

PMID- 17541290
TI  - Consanguineous marriages and their effects on common adult diseases: studies from
      an endogamous population.
AB  - OBJECTIVES: The aim of the study was to determine the extent and nature of
      consanguinity in the Qatari population and its effects on common adult diseases.
      SUBJECTS AND METHODS: The study was conducted in urban and semi-urban areas of
      Qatar between October 2004 and May 2005. The total sample of 1,050 married Qatari
      females 15 years of age and over were approached for study. The degree of
      consanguinity between each female and her spouse and the degree of consanguinity
      between their parents were recorded. RESULTS: Of 1,050 married Qatari females who
      were approached, 876 agreed to participate in the study, giving an 83.4%
      response. The rate of consanguinity in the present generation was 51% (95%
      confidence interval = 47.7-54.4) with a coefficient of inbreeding of 0.023724.
      The consanguinity rate and coefficient of inbreeding in the current generation
      were significantly higher than the maternal rate (51.0 vs. 40.3%; p < 0.001;
      0.023724 vs. 0.016410 maternal). All types of consanguineous marriages were
      higher in this generation, particularly first cousins (26.7 vs. 21.4% paternal
      and 23.1% maternal) and double first cousins (4.3 vs. 2.9% paternal and 0.8%
      maternal). The current generation of consanguineous parents had a slightly higher
      risk for most diseases: cancer, mental disorders, heart diseases, gastro
      intestinal disorders, hypertension, hearing deficit and diabetes mellitus. All
      reported diseases were more frequent in consanguineous marriages. CONCLUSION: The
      study showed that in a population with a high rate of consanguinity, there is a
      significant increase in the prevalence of common adult diseases like cancer,
      mental disorders, heart diseases, gastro-intestinal disorders, hypertension and
      hearing deficit.

PMID- 17541291
TI  - Detection and monitoring of cytomegalovirus infection in renal transplant
      patients by quantitative real-time PCR.
AB  - OBJECTIVES: To establish a sensitive and specific real-time PCR for quantitation
      of cytomegalovirus (CMV) DNA in clinical specimens. SUBJECTS AND METHODS: In a
      prospective study, CMV DNA was quantified in blood samples of 255 kidney
      recipients with and without CMV-related symptoms between the years 2000 and 2005
      in Kuwait. In a selected group of patients, the effect of anti-CMV chemotherapy
      was monitored by quantitative real-time PCR (qRT-PCR). RESULTS: The established
      qRT-PCR assay had a sensitivity to detect 30 CMV DNA copies. CMV DNA was detected
      in 54/255 (24%) patients; of these, 17 (31.5%) were asymptomatic, and 37 patients
      (68.5%) had symptomatic CMV infection. Sequential blood specimens were collected
      from all CMV-positive patients and tested by CMV pp65 antigenemia and qRT-PCR
      assays. There was a moderate positive correlation between the two assays
      (Pearson's correlation = 0.52). The median CMV viral load measured by qRT-PCR was
      higher in symptomatic (6.5 x 10(4) copies/ml) than in asymptomatic (185copies/ml)
      patients (p = 0.001). The estimated cut-off value of CMV DNA for CMV
      symptoms/disease was > or =800 copies/ml of blood. Testing of sequential samples
      from patients treated with symptomatic CMV infection showed that the viral load
      was significantly reduced after 3 weeks of anti-CMV chemotherapy (p = 0.001).
      CONCLUSION: The reported qRT-PCR is a sensitive method for quantitation of CMV
      DNA in the blood of kidney recipients and can be useful in monitoring the
      efficacy of anti-CMV therapy.

PMID- 17541292
TI  - Kuwaiti parents' knowledge of first-aid measures of avulsion and replantation of
      teeth.
AB  - OBJECTIVE: The aim of this study was to assess the knowledge level of emergency
      measures for tooth avulsion among Kuwaiti parents. SUBJECTS AND METHODS: Sixty
      three parents completed an Arabic language questionnaire about their first-aid
      knowledge. The following fields of knowledge were assessed: general body injury
      treatment principles, tooth avulsion and replantation principles, avulsed
      permanent/primary teeth, cleaning of an avulsed tooth before replantation, extra
      alveolar time and storage media. For each category, a score ranging from 0 to 3
      was possible. RESULTS: Experience of first-aid information or training was seen
      in 12 (19%) except for dental injuries, which had not been included in such first
      aid information. Knowledge was demonstrated in 52 (82%) about first aid of minor
      body injuries, yet the knowledge of how to manage avulsed teeth was poor, as 50
      54 (79-86%) parents had no knowledge of how to manage an avulsed tooth in the
      specific modes of treatment measured. There was no difference in knowledge
      between mothers and fathers, young or old, nor was knowledge greater in parents
      with an academic education. CONCLUSION: First-aid knowledge in Kuwaiti parents is
      lacking for avulsion and replantation of teeth despite a high level of knowledge
      of how to manage simple body injuries. Knowledge of first-aid measures regarding
      avulsion and replantation of teeth should be increased by intervention programs.

PMID- 17541293
TI  - Oral health among 35- to 44-year-old Iranians.
AB  - OBJECTIVE: To investigate the oral health status of 35- to 44-year-old Iranians
      in relation to gender, place of residence and education. SUBJECTS AND METHODS: In
      2002, data (n = 8,301) were collected as part of a national survey using WHO
      criteria for sampling and clinical diagnoses across 28 provinces by 33 calibrated
      examiners who performed examinations under a dental light with a WHO probe. The
      study sample was 8,301; male: 3,625 and female: 4,676; urban: 4,854 and rural:
      3,447. Oral health status was assessed by number of decayed (DT), filled (FT) and
      missing (MT) teeth and by DMFT and need for periodontal treatment [community
      periodontal index for treatment needs (CPITN)] indices. Gender, age, place of
      residence and level of education served as socio-demographic information.
      Estimates were adjusted for the 35- to 44-year-old provincial population. ANOVA,
      chi(2) test and logistic regression analysis with odds ratios (OR) and their 95%
      confidence intervals (CI) were the methods of statistical evaluation used.
      RESULTS: The mean number of teeth was 21.5 +/- 6.2, with DMFT: 11.0 +/- 6.4, DT:
      2.6 +/- 2.7, and FT: 1.8 +/- 3.2. DT existed in 6,080 (73%) of the subjects and
      FT in 3,209 (41%). The mean number of FT was greater (p < 0.001) among urban
      residents, women and those with a higher level of education. Only 1% had a CPITN
      of 0; 6% exhibited bleeding, 40% had calculus, 43% shallow and 10% deep pockets.
      Illiterate subjects were more likely to have DT (OR = 1.6, 95% CI = 1.4-1.8) and
      calculus or periodontal pockets (OR = 6.3, 95% CI = 5.1-7.8). CONCLUSION: The
      findings indicate an impaired oral health status in Iranian adults, particularly
      those of low social status and educational level.

PMID- 17541294
TI  - Hemoglobin F concentration as a function of age in Kuwaiti sickle cell disease
      patients.
AB  - OBJECTIVE: This study aimed to document the transition of hemoglobin (Hb) F
      levels from early childhood to adulthood in Kuwaiti sickle cell disease patients,
      investigating its relationship to sex, Hb genotype and coexistence of alpha
      thalassemia trait. SUBJECTS AND METHODS: The following parameters were extracted
      from the patients' records: age, sex, Hb, mean corpuscular volume, mean
      corpuscular Hb, red blood cell count, Hb F, Hb S, Hb A(2) and alpha-globin
      genotype. Hb quantitation was performed with cation exchange HPLC, while alpha
      globin genotype was determined by PCR. RESULTS: Records were available for 149
      patients, made up of 94 SS and 55 Sbeta(0)thal; 83 males and 66 females, aged 3
      months to 60 years (mean 10.5 +/- 1.8). The mean Hb F level in the whole
      population was 21.5 +/- 8.1% and was not significantly different between males
      and females, and SS or Sbeta(0)thal. When the age groups were analyzed, the Hb F
      level was highest (28.9 +/- 10.9%) in those below 5 years. Indeed, patients < or
      =2 years had a mean level of 31.9 +/- 13.0%. There was no significant difference
      in the Hb F levels in SS patients with or without coexistent alpha-thal trait.
      CONCLUSIONS: Kuwaiti sickle cell disease patients below 5 years of age have close
      to 30% Hb F and this is probably a major reason why they usually do not present
      before this age, unlike patients elsewhere who present within the first year of
      life.

PMID- 17541295
TI  - Weight loss attempts among Kuwaiti adults attending the Central Medical Nutrition
      Clinic.
AB  - OBJECTIVES: To investigate the reasons for attempting to lose weight and identify
      weight loss perception and characteristics. METHODS: A cross-sectional survey of
      a sample of 526 Kuwaiti adults was carried out at the Central Medical Nutrition
      Clinic, Kuwait, from August to December 2003. Heights and weights were measured
      and body mass index (BMI) was calculated and classified according to WHO grades
      of obesity. A structured questionnaire used for collecting data was analyzed
      using SPSS version 12.0. RESULTS: Of the 526 subjects, the most commonly cited
      reasons for attempting to lose weight were to avoid health problems (n = 248,
      47.1%) followed by improving personal appearance (n = 141, 26.8%). The weight
      loss perceptions of 263 (50%) of the subjects were within the accepted range (2-5
      kg/month); 321 (61.0%)had previously attempted to lose weight, among them 147
      (45.8%) followed the advice of doctors and dieticians. The major reason mentioned
      for stopping the previous dietary regime was inability to resist sweets and
      traditional foods (n = 99, 31.0%) followed by dissatisfaction with the dietary
      outcome (n = 79, 24.8%). CONCLUSION: The study confirms an awareness of the
      health risks of obesity,but an inability among the dieters to maintain a weight
      loss program. Hence, behavioral management techniques may be necessary to develop
      nutritional education approaches and effective weight management strategies.

PMID- 17541296
TI  - Experimental comparison of bovine-derived xenograft, xenograft-autologous bone
      marrow and autogenous bone graft for the treatment of bony defects in the rabbit
      ulna.
AB  - OBJECTIVES: The purpose of this study was to determine whether bone marrow
      grafted percutaneously has an effect on the healing of bony defects filled with
      bone-derived xenografts. MATERIALS AND METHODS: Eighty New Zealand albino rabbits
      with an average age of approximately 1 year were divided into 4 groups, each
      consisting of 20 animals. Bony defect was induced in the ulnas of all rabbits by
      excising a 1-cm-long bone segment from the 3-cm proximal segment of the right
      distal radioulnar joint. Bone defects were treated simultaneously with bovine
      derived xenograft, a combination of xenograft and bone marrow or on the 5th day
      following the filling of the segment with the xenograft and autogenous bone
      graft. Treatment results obtained for each application type were compared with
      each other with regard to the radiological, biochemical and histological
      criteria. RESULTS: No significant statistical differences were determined between
      the groups in their 15th-day radiographs. The group treated with only xenograft
      from the first month onwards presented with the worst results and was
      significantly different from the other groups with respect to all evaluation
      criteria. No statistically significant difference was determined between rabbits
      treated with xenograft and bone marrow combination and with autogenous bone
      graft. CONCLUSIONS: This study revealed that when xenografts are combined with
      autologous bone marrow, their incorporation into the host bed accelerates
      significantly.

PMID- 17541297
TI  - Assessment of anti-HBs antigen in 6- to 9-year-old children routinely vaccinated
      via vaccination program in Iran.
AB  - OBJECTIVE: To determine persisting antibody levels to hepatitis B virus (HBV)
      antigen in healthy children, aged 6-9 years, vaccinated at birth. METHODS: Blood
      samples were collected from 374 vaccinated children (178 girls and 196 boys) and
      57 unvaccinated children, attending Shiraz Primary School, Shiraz, Iran from
      September 2002 to April 2003. An HBV surface antibody (anti-HBs) was determined
      using enzyme-linked immunosorbent assay. RESULTS: The anti-HBs titer was detected
      in 17% of the 8-year-old children, 7.7% of the 7-year-old children and 46.6% of
      the 6-year-old children. The decrease was greatest in the 9-year-old children;
      more than half (54.3%) had a titer of less than 10 IU/ml, indicating a decrease
      in antibody levels with increasing age/time. Conversely, more than 35% of the 6
      year-old children had a titer greater than 150 IU/ml compared with 24, 12 and 7%
      of children at the age of 7, 8 and 9, respectively, whose antibody titer was less
      than 150 IU/ml. CONCLUSION: Antibody titer declined with time. In comparison with
      other countries, the antibody titer in Iranian children was much lower.

PMID- 17541298
TI  - Impact of viral hepatitis on apo- and lipoprotein status in blood.
AB  - OBJECTIVES: To investigate the effect of viral hepatitis on serum levels of apo-
      and lipoproteins in different forms of liver diseases. MATERIALS AND METHODS: One
      hundred and thirty adult patients and 100 healthy age- and gender-matched control
      individuals participated in this study. Patients were grouped according to four
      types of liver disease: acute viral hepatitis, chronic active hepatitis (CAH),
      cirrhosis of the liver and fulminant hepatic failure. RESULTS: Hepatitis B virus,
      C virus and E virus (HEV) infections were recorded in different combinations in
      these patients, but viral infections of hepatitis A and D were not seen in any of
      the patient groups. The results of lipo- and apoprotein analysis showed different
      patterns. The low-density lipoprotein value was high in the CAH group. In the
      other three groups, low-density lipoprotein level was comparable to the control
      value. The high-density lipoprotein level (p = 0.02) was significantly low in all
      groups except in the cirrhosis group. Apo-A was significantly reduced in the
      acute viral hepatitis and fulminant hepatic failure groups, whereas Apo-B level
      was low in the CAH and cirrhosis groups. The lipoprotein (a) level in these
      groups was low, compared to control. CONCLUSION: No apparent relationship was
      observed between etiological viruses and ensuing changes in lipid/lipoprotein
      profile..

PMID- 17541299
TI  - Supravalvular and valvular aortic stenosis in heterozygous familial
      hypercholesterolemia.
AB  - OBJECTIVES: To report calcified aortic stenosis due to hypercholesterolemia in
      two siblings. CASE PRESENTATION AND INTERVENTION: A 13-year-old boy with a
      history of dyspnea on exertion and a systolic murmur of aortic stenosis was
      referred to our center. Echocardiography showed combined valvular and
      supravalvular aortic stenoses with a good left ventricle systolic function and
      severe left ventricular hypertrophy. Two years later his 17-year-old sister was
      referred to the clinic with similar symptoms. Severe valvular aortic stenosis was
      detected by echocardiography. Selective coronary angiography showed significant
      involvement. The father had a history of hypercholesterolemia and confirmed
      coronary artery disease involving 3 vessels. Angiography showed anterioapical and
      inferiobasal hypokinesis with preserved left ventricle systolic function. The
      mother and the other two siblings did not have hyperlipidemia, thereby indicating
      heterozygous familial hypercholesterolemia in the two affected siblings. The
      siblings were managed with atrovastatin and nicotinic acid and cholestyramine was
      added stepwise. The father was treated with lovostatin. CONCLUSION: This report
      shows that severe hyperlipidemia in very young patients may be a risk factor for
      valvulopathy.

PMID- 17541300
TI  - Chromosome 22q11.2 deletion presenting with immune-mediated cytopenias,
      macrothrombocytopenia and platelet dysfunction.
AB  - OBJECTIVE: To report a case of chromosome 22q11.2 deletion presenting with large
      platelets, platelet dysfunction, immune-mediated thrombocytopenia and
      neutropenia, in addition to other features of the disease. CASE PRESENTATION AND
      INTERVENTION: The patient presented in the neonatal period with tetralogy of
      Fallot, subtle dysmorphic features and thrombocytopenia. Fluorescent in situ
      hybridization analysis confirmed the diagnosis of chromosome 22q11.2 deletion.
      Further investigations showed immune thrombocytopenia and neutropenia in addition
      to reduced expression of platelet GPIb and abnormal platelet aggregation studies.
      CD4:CD8 ratio was reversed. His cardiac abnormality was successfully corrected
      surgically. He had mild recurrent bacterial infections. Recurrent epistaxis was
      becoming increasingly more severe, and he had cognitive developmental and speech
      delay. His serum calcium, phosphorus and parathormone have remained normal.
      CONCLUSIONS: Immune thrombocytopenia can coexist with macrothrombocytopenia and
      platelet dysfunction in chromosome 22q11.2 deletion and may present with
      significant bleeding episodes.

PMID- 17541301
TI  - Inferior vena cava filter as a preventive device for recurrent pulmonary embolism
      in a patient with nephrotic syndrome.
AB  - OBJECTIVE: This study describes a patient with nephrotic syndrome who experienced
      recurrent pulmonary emboli as renal disease relapsed frequently. CLINICAL
      PRESENTATION: A 30-year-old male, who was diagnosed as having nephrotic syndrome
      at 12, presented with general edema, ascites and hypoalbuminemia. Although the
      patient responded well to steroid therapy, a common cold frequently caused flare
      up of nephrotic syndrome. Histopathological examination of renal tissue revealed
      minimal disease change. At 17, the patient had a first pulmonary embolism attack
      with concurrent upper respiratory tract infection. Full-blown manifestations of
      nephrotic syndrome with low antithrombin III levels were identified at that time.
      Anticoagulant therapy was administered to treat the pulmonary embolism. Since the
      first attack, several episodes of pulmonary emboli occurred, which, combined with
      kidney disease, triggered refractory nephrotic syndrome. The nephrotic syndrome
      did not remit, and a secondary renal biopsy identified glomerular pathological
      changes similar to previous biopsy results. To prevent recurrent pulmonary
      emboli, a Greenfield inferior vena cava filter was implanted in April 2002. No
      further pulmonary embolism events occurred after interventional filter
      deployment. CONCLUSION: The results of this study suggest that inferior vena cava
      filter implantation can be effective for preventing recurrent pulmonary embolism
      complicating refractory nephrotic syndrome.

PMID- 17541302
TI  - Thrombotic thrombocytopenic purpura in a patient with Brucella infection is
      highly responsive to combined plasma infusion and antimicrobial therapy.
AB  - OBJECTIVE: To report a case of brucella infection presenting with thrombotic
      thrombocytopenic purpura (TTP) that responded well to plasma and antimicrobial
      treatment infusion. CASE PRESENTATION AND INTERVENTION: A 51-year-old man with
      moderate confusion, depressed mood and dysarthria was admitted. He was
      chronically ill, with fever (38.5 degrees C), anemia, jaundice and petechial
      purpuric skin lesions. Neurological examination revealed diminished consciousness
      with a Glasgow coma scale score of 7 and +1 neck rigidity. The hemoglobin and
      platelet counts were decreased and reticulocyte index, erythrocyte sedimentation
      rate, as well as serum lactate dehydrogenase and renal dysfunction were elevated.
      TTP was a possible diagnosis and the patient responded well to plasma infusion
      and antimicrobial treatment. CONCLUSION: This report shows that therapy of
      underlying infection together with plasma infusion may be a successful treatment
      option for brucellosis-induced TTP.

PMID- 17541303
TI  - 'You're heading in the right direction'. An interview with Dr. Fred Gorelick.
      Interview by Martin E. Fernandez-Zapico.
AB  - In the current interview, the internationally renowned pancreatologist Fred
      Gorelick highlights the key importance of mentorship and gives us a hint of his
      experience in pancreatic research. Dr. Gorelick's discoveries on zymogen
      activation on the pancreatic acinar cell lead the way on the understanding of the
      mechanisms underlying cell damage during pancreatitis. This work opened a new
      field of study and has served as the foundation for subsequent work for a large
      number of laboratories around the world.

PMID- 17541304
TI  - EZH2 polycomb transcriptional repressor expression correlates with methylation of
      the APAF-1 gene in superficial transitional cell carcinoma of the bladder.
AB  - The EZH2 gene controls methylation of various EZH2 target promoters. The APAF-1,
      DAPK-1 und IGFBP-3 genes are frequently methylated in bladder cancer, and
      methylation of these genes is found in more aggressive tumor types. The aim of
      our study was to investigate a potential link between EZH2 mRNA expression and
      the extent of APAF-1, DAPK-1 and IGFBP-3 methylation in urothelial transitional
      cell carcinoma (TCC) and to correlate the data with histopathological parameters
      and follow-up data. EZH2 mRNA expression was measured by real-time reverse
      transcription polymerase chain reaction, and the methylation analysis was
      performed using methylation-specific real-time polymerase chain reaction. Tissue
      specimens were obtained from 35 patients with TCC. EZH2 mRNA expression was
      detected in all tumor specimens investigated. The EZH2 expression levels
      correlated well with the differentiation grade of the tumor specimens (p = 0.03),
      and the APAF-1 methylation correlated with tumor stage (p = 0.0001) and grade (p
      = 0.004). Matched pair analysis demonstrated a statistically significant
      correlation between elevated EZH2 mRNA expression and higher methylation levels
      of APAF-1 in superficial (p = 0.024) and well- differentiated (p = 0.04) TCC. In
      patients with recurrent TCC, APAF-1 and IGFBP-3 methylation levels were
      significantly higher (p = 0.03 and p = 0.01, respectively), which was not
      observed when EZH2 mRNA expression or DAPK-1 methylation levels were related to
      the clinical outcome. In conclusion, our data show that EZH2 expression and APAF
      1 methylation are related to tumor progression and invasiveness. Moreover, these
      data present first evidence that APAF-1 methylation is related to transcriptional
      activity of EZH2 expression in early-stage tumor disease of the bladder.

PMID- 17541305
TI  - Microenvironment effects on promoting upregulation of matrix metalloproteinases
      in Bcl-2-overexpressing renal cell carcinoma as a response to doxorubicin
      treatment inducing the production of metastasis.
AB  - Dysfunction in apoptosis has been suggested to play an important role in the
      development of a distant metastasis. The Bcl-2 gene plays a key role in the
      response to chemotherapeutic agents, and its upregulation protects the cells from
      apoptosis by inactivating the Bax proteins through heterodimerization of Bcl
      2/Bax. However, there is no direct evidence showing that the upregulation of Bcl
      2 increases the antiapoptotic effects against chemotherapeutic agents and is
      associated with the production of a distant metastasis. In this study, the role
      of Bcl-2 in the production of distant metastasis was investigated by examining
      the activity of caspase-3 and the expression of matrix metalloproteinases (MMPs)
      after transfecting the Bcl-2 gene into human renal cell carcinoma cells (SN12C).
      In addition, the production of a distant metastasis was examined in an orthotopic
      animal model. In vitro, the SN12C/smb2 cells were more resistant to doxorubicin
      (DXR) than the untreated parental cells. The IC50 of the SN12C/smb2 was 50%
      higher than that of the parental cells. In addition, the caspase-3 activity of
      the SN12C/smb2 cells was lower than that of the parental cells after the DXR
      treatment. On the other hand, there was no difference in the expression of MMP-2
      and MMP-9 between the SN12C and SN12C/smb2 cell lines. However, the SN12C/smb2
      cells had a higher metastatic potential than the parental cells in the orthotopic
      animal model. Unlike the results from the in vitro analysis, the expression of
      MMP-2 and MMP-9 in the kidney tumors produced by the SN12C/smb2 cells was higher
      than in the kidney tumors produced by the SN12C/vector. These results show that
      the upregulation of Bcl-2 in human renal cell carcinoma cells induces drug
      resistance to DXR. Moreover, Bcl-2 induced the expression of MMP in tumors grown
      in the orthotopic sites even though no appreciable effects were observed in the
      in vitro condition. When the in vitro and in vivo data were combined, it appears
      that the Bcl-2 gene initially affects the response to DXR. The cells that survive
      the DXR treatment then have a chance to become metastatic by increasing the
      levels of MMP in an orthotopic environment.

PMID- 17541306
TI  - Effect of chronic sustained-release dipyridamole on myocardial blood flow and
      left ventricular function in patients with ischemic cardiomyopathy.
AB  - Dipyridamole increases adenosine levels and augments coronary collateralization
      in patients with coronary ischemia. This pilot study tested whether a 6-month
      course of sustained-release dipyridamole/aspirin improves coronary flow reserve
      and left ventricular systolic function in patients with ischemic cardiomyopathy.
      Six outpatients with coronary artery disease and left ventricular ejection
      fraction (LVEF) <40% were treated with sustained-release dipyridamole 200
      mg/aspirin 25 mg twice daily for 6 months. Myocardial function and perfusion,
      including coronary sinus flow at rest and during intravenous dipyridamole-induced
      hyperemia, were measured using velocity-encoded cine magnetic resonance stress
      perfusion studies at baseline, 3 months, and 6 months. There was no change in
      heart failure or angina class at 6 months. LVEF increased by 39%+/-64% (31.0%+/
      13.3% at baseline vs 38.3%+/-10.7% at 6 months; P=.01), hyperemic coronary sinus
      flow increased more than 2-fold (219.6+/-121.3 mL/min vs 509.4+/-349.3 mL/min;
      P=.01), and stress-induced relative myocardial perfusion increased by 35%+/-13%
      (9.4%+/-3.4% vs 13.9%+/-8.5%; P=.004). Sustained-release dipyridamole improved
      hyperemic myocardial blood flow and left ventricular systolic function in
      patients with ischemic cardiomyopathy.

PMID- 17541307
TI  - "I am not alone": the feasibility and acceptability of interactive voice response
      facilitated telephone peer support among older adults with heart failure.
AB  - Patient self-management is a critical determinant of heart failure (HF) outcomes,
      yet patients with HF are often frail and socially isolated, factors that may
      limit their ability to manage self-care and access clinic-based services.
      Mobilizing peer support among HF patients is a promising strategy to improve self
      management support. In this pilot, the authors evaluated the feasibility and
      acceptability of an interactive voice response (IVR)-based platform to facilitate
      telephone peer support among older adults with HF. Participants completed a
      baseline survey, were offered a 3-hour training session in peer communication
      skills, and were paired with another patient who had HF. Participants were asked
      to contact their partner weekly using a toll-free IVR phone system that protected
      their anonymity and provided automated reminders if contacts were not made. Times
      and duration of participants' telephone contacts were monitored and recorded.
      After the 7-week intervention, participants completed surveys and brief face-to
      face interviews. The authors found high levels of use and satisfaction and
      improvements in depressive symptoms among the 20 pilot study participants. An IVR
      peer-support intervention is feasible, is acceptable to patients, and may have
      positive effects on patients' HF social support and health outcomes, in
      conjunction with structured health system support, that warrant more rigorous
      evaluation in a randomized trial.

PMID- 17541308
TI  - Factors determining extreme brain natriuretic peptide elevation.
AB  - Brain natriuretic peptide (BNP) level is elevated in heart failure and reflects
      its severity. It is unknown why some patients have extremely high BNP levels. The
      authors retrospectively reviewed data on 179 consecutive patients whose BNP
      levels fell within one of several predetermined ranges: mild elevation, 500 to
      1000 pg/mL (n=82); moderate elevation, 2000 to 3000 pg/mL (n=48); and high
      elevation, 4000 to 20,000 pg/mL (n=49). The statistical analysis was conducted
      with the unpaired t test and Pearson's correlation coefficient. Adjustments were
      made for age, sex, and serum creatinine level. Patients with moderate BNP
      elevation were more symptomatic and had more advanced structural and hemodynamic
      changes than did patients with lower BNP elevation. Characteristics of the high
      BNP level group did not differ from those of the moderate BNP level group. Serum
      creatinine level correlated with BNP level, but neither age nor sex did. High BNP
      level (4000-20,000 pg/mL) is determined more by renal dysfunction than by the
      severity of heart failure.

PMID- 17541309
TI  - Elevated serum cardiac markers predict coronary artery disease in patients with a
      history of heart failure who present with chest pain: insights from the i*trACS
      registry.
AB  - The significance of a history of heart failure (HF) in patients presenting with
      acute coronary syndromes and elevated cardiac markers is unclear. The authors
      performed an analysis of patients enrolled in the Internet Tracking Registry of
      Acute Coronary Syndromes (i*trACS). Cardiac marker measurement and cardiac
      catheterization were performed in 1174 patients. Of these, 116 (9.9%) had heart
      failure (HF). Coronary artery disease (CAD) was found in 61 (52.6%) patients in
      the HF group and 581 (54.9%) in the group without HF. In the non-HF cohort,
      positive markers occurred in 306 patients, in whom 217 (70.9%) had CAD at
      catheterization. In the HF subset, 24 patients had positive biomarkers and 15
      (62.5%) had CAD. A history of HF did not lessen the likelihood of CAD as
      evidenced by angiography and does not diminish the utility of cardiac markers in
      diagnosing acute coronary syndromes.

PMID- 17541310
TI  - Clinical findings, natriuretic peptides, and echocardiography: integrating tools
      to optimize heart failure management.
AB  - The hemodynamic profile of heart failure (HF) patients may be critical to their
      clinical outcome, whereby congestion emerges as a particularly important aspect
      to define therapeutic goals, optimize HF treatment, and determine prognosis.
      Accordingly, individualized HF management must include several strategies to
      detect congestion, which might easily be underestimated in chronic HF patients.
      Therefore, it is important to recognize the true reliability of traditional HF
      signs and symptoms. The contemporary understanding of HF has brought new value to
      some aspects of physical examination. Natriuretic peptides have emerged as
      potential new tools in the diagnosis of congestion in patients with HF, and
      echocardiography has gained renewed importance in HF management when it is used
      to investigate hemodynamic profile. The aim of this article is to review and
      integrate these 3 ways of assessing and monitoring HF patients: clinical
      findings, natriuretic peptides, and echocardiography.

PMID- 17541311
TI  - Right ventricular failure in patients with preserved ejection fraction and
      diastolic dysfunction: an underrecognized clinical entity.
AB  - It is well recognized that patients with severe left ventricular (LV) systolic
      dysfunction develop pulmonary venous hypertension or postcapillary pulmonary
      hypertension, which leads to an increase in pulmonary vascular resistance (PVR)
      and right ventricular (RV) systolic failure. It is often underrecognized,
      however, that patients with heart failure with preserved LV ejection fraction and
      diastolic dysfunction may also develop postcapillary pulmonary hypertension with
      elevated PVR leading to RV systolic failure. This form of biventricular failure
      is a result of diastolic failure on the left in patients with preserved LV
      ejection fraction and systolic failure on the right. At this time, there are no
      randomized trials or guidelines addressing the management of patients with
      diastolic heart failure with and without resultant RV failure. The authors review
      the pathophysiology, clinical presentation, and suggested treatment of this
      underrecognized clinical entity.

PMID- 17541312
TI  - Novel strategies: challenge loop diuretics and sodium management in heart failure
      -part II.
AB  - The conflicting results of diuretic treatments in heart failure (HF) and the
      importance of Na management in the context of the cardiorenal syndrome and
      neurohormonal activation in HF have suggested novel and counterintuitive
      strategies, focused primarily on the use of vasopressin antagonists and
      hypertonic saline solution with high doses of loop diuretics and their
      neurohormonal interference. The emerging novel therapies involving direct
      inhibition of vasopressin receptors appear to show promising results. The use of
      hypertonic saline solution mixed with a high dose of loop diuretics produces,
      probably by indirect mechanisms, a reduction or inhibition of the activated
      neurohormonal systems in HF patients. This treatment opens a new window on the
      role of sodium management in these patients and on the relation between sodium
      and the kidney's role and function in heart failure. The authors review the
      current evidence for these therapies and suggest hypothetical bases for their
      efficacy.

PMID- 17541313
TI  - The obesity paradox and discrepancy between peak oxygen consumption and heart
      failure prognosis--it's all in the fat.
AB  - The authors present the case of an obese patient with advanced heart failure that
      demonstrates the paradox between obesity and heart failure prognosis. In
      addition, the authors discuss the rationale for the correction of cardiopulmonary
      stress data (used as predictors of survival and listing for cardiac
      transplantation) for lean weight (as opposed to total body weight), a
      consideration that may be particularly important in obese patients with a high
      percentage of body fat.

PMID- 17541314
TI  - History of heart failure.

PMID- 17541315
TI  - Development and testing of the Survey of Illness Beliefs in Heart Failure tool.
AB  - This study establishes reliability and construct validity of the Survey of
      Illness Beliefs in Heart Failure (HF) tool, which measures the accuracy and
      certainty of illness beliefs people have about HF. Factor analysis produced a 2
      component structure of 14 items that revealed accurate and inaccurate illness
      beliefs (alpha=0.87 and 0.71, respectively). Construct validity was supported
      with significantly greater accuracy in illness belief scores in patients
      evaluated or listed for heart transplantation or enrolled in an HF research study
      (P=.008 and .02, respectively). The reliability and validity of the tool is
      sufficient to support its use in clinical research.

PMID- 17541316
TI  - Physical function and quality of life in older women with diastolic heart
      failure: effects of a progressive walking program on sleep patterns.
AB  - This preliminary study tested the effects of a home-based walking intervention on
      total sleep time (TST), nocturnal awakenings, depressive symptoms, physical
      function, and quality of life (QOL) in older women with diastolic heart failure
      (DHF). Twenty-three women (mean age, 68+/-11 years) with New York Heart
      Association class II or III DHF were randomized to either a 12-week home-based
      walking intervention (n=13) or education-only program (control, n=10). No between
      group differences were found in women in the intervention and control groups on
      any of the outcome variables. When outcomes were compared within each group at
      baseline and 12 weeks, intervention-group patients had improvement in TST (P<.01)
      and heart failure-related QOL (P<.05) and a trend for decreased depressive
      symptoms (P<.07). Women randomized to the control group had no change in any
      outcomes. These preliminary findings suggest that a progressive walking program
      may improve TST and QOL in older women with DHF. Findings from this study support
      the need for larger studies to evaluate the long-term benefits of a walking
      program on sleep patterns, QOL, and psychologic function in this population.

PMID- 17541317
TI  - Usefulness of RISKO Heart Hazard Appraisal to Quantify CAD risk factor burden on
      the preoperative functioning of coronary artery bypass graft surgery patients.
AB  - The preoperative status of coronary artery bypass graft (CABG) surgical patients
      is often evaluated as a means to assess operative risk for mortality and
      morbidity and to inform how preoperative status influences or predicts outcomes
      following CABG surgery. The purpose of this study was to examine the influence of
      coronary artery disease (CAD) risk factor burden on CABG patients' preoperative
      functioning (functional status and functional capacity). A convenience sample of
      152 subjects, 65 years and older, who had been consecutively enrolled in a larger
      randomized clinical trial, was evaluated. The RISKO Heart Hazard Appraisal was
      used to quantify CAD risk factor burden of the subjects. There were significant
      differences by CAD risk factor burden group, with subjects in the highest CAD
      risk factor burden group having poorer general health functioning (F2,147=3.45;
      P<.05) and functional capacity (F2,147=5.43; P<.01). These findings elucidate the
      potential usefulness of evaluating CABG patients' preoperative CAD risk factor
      burden status.

PMID- 17541318
TI  - Cardiac rehabilitation: a comprehensive program for the management of heart
      failure.
AB  - Heart failure is one of the major health problems found in the United States
      today. Medical and interventional therapies play an important role in the
      treatment of this chronic condition, but they create a huge economic burden on
      the health care system. Nonpharmacologic interventions need further exploration.
      This article reviews research that examined the relationship between exercise and
      heart failure. A variety of exercise modalities measured outcomes of functional
      capacity and quality of life in both supervised and nonsupervised settings. Many
      investigators found exercise training to be safe and to confer benefits,
      especially on functional capacity, quality of life, and survival. The most
      favorable outcomes were observed in supervised settings. Cardiac rehabilitation
      provides an ideal environment for safe exercise and management of the health care
      needs of patients with heart failure. The multidisciplinary staff is adept at
      providing a paced approach to activity based on individualized exercise
      prescriptions, education, and management of this population's many comorbidities.

PMID- 17541319
TI  - Sleep disturbances in caregivers of patients with end-stage congestive heart
      failure: Part II--assess and intervene.
AB  - Sleep disturbances in caregivers of patients with congestive heart failure is
      common. The consequences of sleep disturbances are dire and have potential to
      seriously impact caregiver health and patient outcomes. Therefore, it is
      imperative that the health care team, especially nurses, assess and intervene.
      Basic assessment of caregiver sleep disturbance can be quick and simple and can
      be performed while assessing the congestive heart failure patient's health. If a
      more complex sleep disorder is suspected, other assessments can be conducted if
      time and money permit. The benefits to properly assessing sleep disturbance and
      subsequent treatment far outweigh the minimal time spent by the health care team
      or caregiver.

PMID- 17541320
TI  - Update on the interaction of rifampin and warfarin.
AB  - A 79-year-old man with a history of deep vein thrombosis and pulmonary embolism
      received anticoagulation therapy with warfarin 5 mg daily for 8 months. He was
      diagnosed with osteomyelitis and underwent partial metatarsal resection of his
      right foot. After surgery, antibiotics were initiated, including ertapenem sodium
      1 g intravenously every 24 hours, vancomycin 1400 mg intravenously every 24
      hours, and rifampin 300 mg by mouth twice daily. Achieving a therapeutic level of
      anticoagulation was difficult despite escalating doses of warfarin, because of
      the interaction with rifampin. A 5- to 6-fold increase in warfarin dose was
      prescribed to reach therapeutic international normalized ratios (INRs), but even
      these increases were insufficient to maintain his INR in the therapeutic range.
      After rifampin was discontinued, warfarin doses were gradually reduced over the
      next 2 months. When concurrent warfarin-rifampin therapy is necessary, vigilant
      monitoring is imperative and significant increases in warfarin doses are likely.

PMID- 17541321
TI  - Cardiac cachexia at a glance.

PMID- 17541322
TI  - Pharmacogenomics and the potential for personalized therapeutics in
      cardiovascular disease.

PMID- 17541323
TI  - Why do we need to prevent right ventricular pacing?

PMID- 17541324
TI  - The many faces of heart failure.

PMID- 17541325
TI  - ACE inhibitors and ARBs: are they better than other agents to slow nephropathy
      progression?

PMID- 17541326
TI  - Patient and provider perceptions of hypertension treatment: do they agree?
AB  - The objective of our study was to explore physician and patient attitudes
      regarding hypertension management. One hundred forty-five primary care providers
      and 189 patients with hypertension at 6 Veterans Administration clinics completed
      a hypertension survey. Fifty-one percent of patients were at their blood pressure
      goal, 58% were on guideline-concordant therapy, and 31% achieved both. Patients
      and providers agreed that physicians were a "very/extremely" useful source of
      information but differed in perceived value of pharmacists, educational material,
      advertising, and the Internet. They also agreed on the value of preventing
      cardiovascular events but differed in their perceptions of the importance of
      medication costs, side effects, and national guidelines. Blood pressure control
      and guideline-concordant therapy was higher than most prior reports, but with
      opportunity for improvement. Patients and providers differed in perceived value
      of various aspects of hypertension management; this information may help to
      determine trial design and quality improvement strategies in the future.

PMID- 17541327
TI  - Prehypertension and insulin resistance in a nationally representative adult
      population.
AB  - Prehypertension is associated with increased risk of cardiovascular disease and
      progression to hypertension. Insulin resistance (IR) is also related to
      cardiovascular risk. It is unknown whether individuals with prehypertension also
      have higher IR. The purpose of this study was to examine the association between
      prehypertension and IR. The National Health and Nutrition Examination Survey 1999
      2002 was used to determine odds of IR by fasting insulin level >12.2 microU/mL or
      homeostasis model assessment (HOMA) > or = 2.6 among nondiabetic adults aged 20
      to 80 years across blood pressure categories. Compared with normotensives, odds
      of IR were over 60% higher for prehypertensive individuals by both IR measures:
      fasting insulin (odds ratio [OR], 1.67; 95% confidence interval [CI], 1.12-2.48)
      and HOMA (OR, 1.67; 95% CI, 1.22-2.30). After stratifying by sex, IR was
      associated with prehypertension in only men for both IR measures. In conclusion,
      prehypertension is associated with higher IR in men, which may confer additional
      cardiovascular disease risk.

PMID- 17541328
TI  - Effects of candesartan and lisinopril on the fibrinolytic system in hypertensive
      patients.
AB  - The effects of the angiotensin II receptor blocker candesartan and the
      angiotensin-converting enzyme inhibitor lisinopril on the fibrinolytic system
      were investigated in a double-blinded, prospective, randomized study. Seventy
      seven hypertensive patients taking candesartan (n=41) and lisinopril (n=36) with
      a systolic blood pressure >130 mm Hg and/or a diastolic blood pressure >80 mm Hg
      obtained by 24-hour ambulatory blood pressure measurement were included in the
      study. Blood pressure, plasminogen activator inhibitor 1 (PAI-1), tissue
      plasminogen activator (tPA), and the molar ratio of PAI-1/tPA were determined
      before treatment and 6 weeks later. Blood pressure decreased in both groups
      (candesartan, 155/85 mm Hg to 140/84 mm Hg; P<.05; lisinopril, 152/85 mm Hg to
      138/83 mm Hg; P<.05). The fibrinolytic balance was significantly different
      between treatment groups (molar ratio of PAI-1/tPA: candesartan, 3.66 [2.2;]
      lisinopril, 5.44 [2.6;] P<.05). In contrast to lisinopril, the balance between
      coagulation and fibrinolytic activity shifted toward fibrinolysis during
      candesartan treatment.

PMID- 17541329
TI  - Coronary heart disease events preventable by control of blood pressure and lipids
      in US adults with hypertension.
AB  - Hypertension (HTN) and dyslipidemia are major risk factors for coronary heart
      disease (CHD). In 676 (projected to 26.1 million) US persons from the National
      Health and Nutrition Examination Survey (NHANES) 2001-2002 with HTN, the authors
      estimated the preventable CHD events from statistical control of blood pressure
      (BP) and lipid levels. Using Framingham algorithms, the authors projected the CHD
      events that could be prevented from statistical control of BP, low-density
      lipoprotein cholesterol, and high-density lipoprotein cholesterol. If BP was
      controlled to nominal levels, the authors projected 19% of CHD events (37% if
      controlled to optimal) would be prevented. Improving lipid levels to nominal
      levels was estimated to prevent 27% of CHD events (62% if controlled to optimal).
      Combined control of BP and lipid levels to nominal levels was projected to
      prevent 38% of CHD events (76% if controlled to optimal). The authors' results
      demonstrate that combined control of BP and lipid levels may prevent the majority
      of CHD events in Americans with HTN.

PMID- 17541330
TI  - Blood pressure management in acute ischemic stroke.
AB  - Data from the Project for Improvement of Stroke Care Management in Minnesota were
      used to characterize provider practice in the management of hypertension in
      hospitalized acute ischemic stroke patients in relation to guidelines from the
      American Stroke Association (ASA) and the European Stroke Initiative (EUSI).
      Among 1181 patients, 129 received as-needed medication in direct response to
      elevated blood pressure in the first 24 hours after admission. Of these 129, 56%
      were overtreated according to ASA guidelines and 24% by EUSI guidelines. Of the
      1052 patients not treated, 16% were undertreated by ASA guidelines and 3% by EUSI
      guidelines. In contrast, discharge hypertension was well treated, with 93% (424
      of 454) of patients likely to have chronic hypertension appropriately treated
      with antihypertensive medication on discharge. These findings support the need
      for more research to fill identified gaps in evidence, improve treatment
      guidelines, and reduce variability in patient management.

PMID- 17541331
TI  - The pathophysiologic role of the brain renin-angiotensin system in stroke
      protection: clinical implications.
AB  - The brain possesses the same renin-angiotensin system (RAS) as the systemic
      circulation. Recent experimental studies have shown that the brain RAS plays an
      important role in stroke and neuronal protection through its effector peptide
      angiotensin (Ang) II. Ang II exerts its stroke-protective effects through
      stimulation of Ang II type 2 (AT2) receptors. Angiotensin receptor blockers
      (ARBs) exert a dual influence, which is important in their stroke protective
      effects. They selectively block the Ang II type 1 (AT1) receptors, decreasing
      local vasoconstriction, and allow free Ang II to stimulate the unoccupied AT2
      receptor and increase local vasodilation, resulting in the alleviation of local
      brain ischemia and limiting the volume and extent of brain loss. In contrast,
      angiotensin-converting enzyme (ACE) inhibitors, by decreasing the amount of Ang
      II production, may diminish the stroke-protective effects of Ang II. This perhaps
      could be a reason for the inferior stroke-protective effect of ACE inhibitors
      compared with ARBs, which has been demonstrated in several clinical trials. The
      evidence for this effect of ARBs compared with ACE inhibitors, however, is only
      indirect. Ongoing clinical trials with head-to-head comparisons of ARBs and ACE
      inhibitors will hopefully provide the needed information.

PMID- 17541332
TI  - Statins and blood pressure: is there an effect or not?
AB  - In addition to the lipid-lowering effects of statins, several basic and clinical
      studies in recent years have examined the effects of these agents on other
      cardiovascular parameters. Some of these studies investigated the general impact
      of a statin on blood pressure (BP) among various other factors, while others were
      specifically designed to determine this effect. Data from animal studies are
      conflicting but the majority of human studies in the field report a beneficial
      effect, and most available statin compounds are reported to lower BP levels.
      Recent clinical studies using ambulatory BP measurements support these findings.
      Although the exact actions of statins involved in this effect are unknown,
      several possible mechanisms can be hypothesized. This review summarizes existing
      data on the effect of statins on BP, aiming to give an overview of the current
      knowledge and to provide perspectives for future research in the field.

PMID- 17541333
TI  - Primary hyperaldosteronism: returning to the limelight?

PMID- 17541335
TI  - Screening by anti-endomysium antibodies for celiac disease in Tunisian children
      with type 1 diabetes mellitus.
AB  - AIM: Celiac disease (CD) and type 1 diabetes mellitus (DM1) can frequently
      coexist, presumably due to a common genetic predisposition. The present study was
      designed to evaluate the frequency of CD among Tunisian children with DM1.
      PATIENTS AND METHODS: A total of 205 diabetic children (92 girls, 113 boys, age
      range 6 months-15 years, median 11 years) were screened for CD by determination
      of IgA anti-endomysium antibodies (EMA). RESULTS: EMA were positive in 17 out of
      205 (8.3%) children with DM1. The median age of DM1 at onset was significantly
      lower in patients with EMA than those without EMA (P<10(-7)). In 13 of 17 EMA
      positive patients, duodenal biopsy could be performed and a destructive type of
      CD was confirmed in 11 of them: 8 patients showed total villous atrophy, 3
      patients showed a partial villous atrophy. The other two patients showed a normal
      histological picture with normal number of intraepithelial lymphocytes. Parents
      of the remaining EMA-positive children refused endoscopy. Thus the prevalence of
      biopsy-proven CD was 5.3% (11/205). It was 7.6% (7/92) in girls and 3.5% (4/113)
      in boys but the difference was not statistically significant. Seventy three
      percent of patients with CD were asymptomatic. CONCLUSIONS: The prevalence of
      clinically unrecognized CD, found by EMA screening, is high in Tunisian children
      with DM1. We suggest that children with diabetes should be screened for CD.

PMID- 17541336
TI  - [Intestinal transplantation].
AB  - Even though surgical techniques for isolated intestine, liver-intestine, and
      multivisceral transplantations were developed in the 1960's, very few patients
      were transplanted before 1990 because initial immunosuppression regimens were
      insufficient, making intestine transplantation impossible. Intestine
      transplantation resulted in death in most patients within days or months. The
      discouraging results of the first clinical trials were due to technical
      complications, sepsis, and the failure of conventional immunosuppression to
      control rejection. By 1990 the development of tacrolimus-based immunosuppression
      and improved surgical techniques, the increased array of potent immunosuppressive
      medications, infection prophylaxis, and suitable patient selection helped improve
      actuarial graft and patient survival rates for all types of intestine
      transplantation. The aims of this review are to describe the current status of
      intestine transplantation including the underlying diseases and conditions that
      may be indications for intestine transplantation, to identify patient populations
      for this indication, to provide key steps for patient evaluation, to summarize
      current recommendations for immunosuppression, to list the most common
      postoperative complications, and to discuss the international experience of small
      bowel transplantation compiled and analyzed by the International Intestine
      Transplant Registry since 1985.

PMID- 17541338
TI  - Hepatitis C awareness among adolescents in the Alpes-Maritimes area of France.
AB  - OBJECTIVES: Certain practices with a potential risk of hepatitis C virus (HCV)
      transmission begin early, during adolescence. In 2004, primary prevention
      interventions targeting adolescents aged 13-17 years attending school in the
      Alpes-Maritimes region of France were conducted by the "Reseau Hepatite C Ville
      Hopital Cote d'Azur". The aim of this study was to assess the adolescents'
      knowledge about HCV and to evaluate the impact of such interventions. METHODS: A
      random sample of secondary state schools in the Alpes-Maritimes was invited to
      participate in the study. Before and after presenting a slide show about HCV in
      the selected classrooms, the investigators asked the students to complete an
      anonymous self-administered questionnaire designed to assess their knowledge
      about HCV infection. RESULTS: The intervention concerned a study population of
      2,946 students, mean age 14.4 +/- 2.5 years. Before the interventions, 21% had
      good knowledge of HCV infection and 24% had good know-ledge of disease contagion.
      These percentages increased significantly after the interventions to 95% and 84%
      respectively. Knowledge improvement was more significant among high school
      students and among students whose parents had an employment. CONCLUSIONS:
      Adolescents are poorly informed about HCV infection. The present intervention
      enabled significant improvement in their knowledge about the infection and
      disease contagion, independently of gender, age and geographical area.

PMID- 17541337
TI  - Routine practice HCV infection screening with saliva samples: multicentric study
      in an intravenous drug user population.
AB  - OBJECTIVE: The purpose of this randomized multicentric study was to evaluate the
      diagnostic contribution of screening for HCV infection on saliva samples in day
      to-day practice in the intravenous drug-user (IVDU) population. METHODS: Between
      January and May 2004, 274 presumably HCV-negative IVDU were screened for HCV
      infection in 15 centers in France (median age 29 years). After centralized
      randomization, screening tests were performed on blood samples (arm A) or saliva
      samples (arm B). Screening tests were performed in 78 subjects (28%) had never
      been screened before and in 196 subjects (72%) who had had a negative HCV
      screening test on average 12 months prior to the beginning of the study. In the
      event of a positive saliva test for anti-HCV Ab, a serum test for anti-HCV Ab was
      performed. In the event of a positive serum test for anti-HCV Ab, PCR was
      performed on serum to measure HCV-RNA. RESULTS: Fourteen individuals were
      positive for HCV RNA (7 in each arm). Six of these cases had not been detected
      before. In eight cases, the median time between the last negative screening test
      and study inclusion was 11 months (range 6-94 months). CONCLUSIONS: Viremia tests
      were positive in 5% percent of the target population, although one-third of the
      individuals in arm A (blood samples) were not tested. The saliva test may be a
      useful alternative in the event of refusal of a blood test or when poor venous
      conditions compromise venous puncture. A confirmatory blood test still remains
      difficult to obtain in nearly half of patients.

PMID- 17541339
TI  - Appendectomy, smoking habits and the risk of developing ulcerative colitis: a
      case control study in private practice setting.
AB  - OBJECTIVES: The strongest environmental factors identified for ulcerative colitis
      (UC) are cigarette smoking and appendectomy. However, most studies have been
      performed using case-controls from hospital-based populations. The purpose of
      this study was to compare the history of previous appendectomy and smoking habits
      in a group of patients with UC and a control group, followed by
      gastroenterologists in private practice. METHODS: We performed a case control
      study in which 100 physicians recruited UC-patients and age and sex matched
      controls. Data were collected during a single visit. Based on a standardized
      questionnaire, UC patients and controls were divided into never, former or
      current smokers, and into subjects with or without a previous history of
      appendectomy. RESULTS: One hundred and ninety eight age- and sex-matched pairs of
      UC patients and controls were included. The prevalence of appendectomy in the UC
      patients and control group was 12% and 46%, respectively. The pairwise-matched OR
      of ulcerative colitis for previous appendectomy was 0.10 (95% CI, 0.05-0.21)
      (P<0.0001). The OR for former and never smokers versus current smokers was 2.40
      (95% CI 1.31-4.38) (P=0.004). In UC-patients, the OR of family history of UC
      compared with controls was 2.80 (95% CI, 1.01-7.77) (P=0.048). CONCLUSIONS: This
      case-control study confirmed a strong negative correlation between both
      appendectomy and tobacco smoking, and ulcerative colitis in patients followed-up
      by gastroenterological practitioners.

PMID- 17541341
TI  - [Why and how to evaluate liver fibrosis in 2007].

PMID- 17541342
TI  - Guidelines for the diagnosis of uncomplicated cirrhosis.

PMID- 17541343
TI  - [Characteristics and interpretation of blood tests for liver fibrosis].

PMID- 17541344
TI  - [Use of elastometry (FibroScan) for the non-invasive staging of liver fibrosis].

PMID- 17541346
TI  - [Establishment of the intestinal microflora in neonates].
AB  - The intestinal microbiota is a complex ecosystem harbouring about 10(14) micro
      organisms composed of nearly 400 hundred species. It plays various important
      functions in the gut, including metabolic, flora, barrier and stimulation of the
      intestinal immune system. Most studies have been based on culture, but more
      recent molecular biology techniques have provided complementary information. The
      formation of this ecosystem begins rapidly in the newborn; it is sterile at birth
      and is based on contact with the maternal flora and the surrounding environment.
      Although little is known about the factors leading to the development of
      bacteria, numerous external factors will affect the microbial succession: mode of
      delivery, environmental conditions, type of feeding, gestational age, and
      antibiotics. Recent data report a delay in intestinal colonization especially of
      enteric maternal bacteria. Which may be due to strict hygiene measures during
      birth. The clinical impact of these variations is not known but they could lead
      to lack of barrier flora or poor immune system stimulation in the gut. Modulation
      of gut microbiota in neonates with infant formulas containing either probiotics,
      prebiotics or non viable bacterias and their metabolites, or nucleotides is
      discussed.

PMID- 17541347
TI  - [Acinar cell carcinoma of the pancreas with predominant intraductal growth:
      report of a case].
AB  - Acinar cell carcinoma (ACC) of the pancreas accounts for approximately 1% of all
      exocrine pancreatic tumours. We report a rare form of ACC in a 66-year-old man.
      This tumour was revealed by epigastric pain and weight loss. Abdominal computed
      tomography showed a hypodense, well-demarcated, heterogeneous lesion, in the head
      of the pancreas, measuring 4.2 cm in diameter. There was a marked dilatation of
      the main pancreatic duct upstream, with tumour spreading within this duct. The
      diagnosis of ACC was made on the fine needle aspiration cytology performed during
      endoscopic ultrasound examination. On the pancreaticoduodenectomy specimen, the
      dilated main pancreatic duct (2.5 cm in diameter) was filled by an exophytic
      tumour. Histological examination showed an ACC, with predominant intraductal
      growth (main and accessory pancreatic ducts), with pancreatic parenchymal and
      duodenal invasion. Neuroendocrine markers were negative. To our knowledge, this
      is the second report of an ACC with predominant intraductal spread. These rare
      forms of ACC can be confused with intraductal papillary-mucinous neoplasms. In
      our report, fine needle aspiration cytology performed during endoscopic
      ultrasound examination was a valuable tool in the diagnostic assessment.

PMID- 17541348
TI  - [Suspected malignant cancer of the pancreas associated with pseudo-invasive
      duodenal hamartomas in a patient with Peutz-Jeghers syndrome].
AB  - A 29-year-old man with a previously known Peutz-Jeghers syndrome (PJS) was
      admitted for epigastric pain, emesis and weight loss due to both intestinal
      intussusception causing bowel obstruction and obstructive pancreatitis. The
      patient had cholestasis with an enlarged common bile duct on imaging. Because
      duodenal and/or pancreatic cancer was suspected due to weight loss, the
      pancreatic and bile duct obstruction, and the increased risk of small intestine
      and pancreatic adenocarcinoma in patients with PSJ, a pancreatoduodenectomy was
      performed. Pathological examination revealed a duodenal polyp with epithelial
      misplacement invading the ampulla and compressing the main bile duct. Twenty
      months after surgery, there was no relapse of symptoms or cholestasis. This is
      the first case showing a direct role of pseudo-invasive duodenal harmatomas in
      the development of biliary obstruction and chronic obstructive pancreatitis.

PMID- 17541349
TI  - [Ewing sarcoma of the mesocolon].
AB  - This case-report studies the clinical, radiological, anatomopatholo-gical and
      therapeutic aspects of peripheral primitive neuroectodermal tumours (PNET). PNET
      are neoplasms with a similar histology to tumours in the Ewing family. Diagnosis
      requires histopathology, immunohistochemistry and cytogenetic studies. To our
      knowledge, this rare tumour has never been reported in the mesocolon (our case).
      The treatment, which is usually similar to that for Ewing's sarcoma is complex
      and has not yet been codified, which is another difficult aspect of this disease
      with a poor prognosis.

PMID- 17541350
TI  - [Symptomatic hepatic angiomyolipoma].

PMID- 17541353
TI  - [Elastography: an old concept for a new tool].

PMID- 17541354
TI  - [Increasing role of MRI for detection and staging of breast cancer].

PMID- 17541355
TI  - [Testicular adrenal rests: the role of imaging].
AB  - Testicular adrenal rests are encountered in ACTH hypersecretion syndromes, most
      often in congenital adrenal hyperplasia attributable to a deficit in 21
      hydroxylase. They are discovered clinically or on systematic sonography,
      generally in the young adult. On sonography, they appear as confluent
      hypoechogenic masses, often bilateral, that have developed in the region of the
      testicular hilum. At a late stage, they take on a highly suggestive attenuating
      aspect. In color Doppler, they have a regular vascular architecture. They
      generally regress or stabilize with replacement glucocorticosteroid treatment.
      They can sometimes progress, which then poses the problem of the type of lesion.
      Biopsy or spermatic vein samples are not reliable. MRI contributes very little
      more than sonography. Diagnosis comes with follow-up or, as a last resort,
      orchidectomy.

PMID- 17541356
TI  - [Radiological management of vascular lesions secondary to pelvic injuries].
AB  - Pelvic injuries are serious, with mortality higher than 40% if the patient is in
      shock upon arrival at the hospital. These injuries are generally secondary to
      traffic accidents with violent kinetics, which explains the frequency of the
      associated extrapelvic lesions. With the vital prognosis at stake, management of
      these patients is a true challenge from both the radiographic and emergency care
      points of view. The objectives of this review are to present the epidemiological
      and physiological issues involved in pelvic injuries and the place of imaging
      today, necessarily integrated within a multidisciplinary team associating
      emergency physicians, surgeons, radiologists, and biologists.

PMID- 17541357
TI  - [Imaging spinal cord cystic lesions in adults].
AB  - Intrarachidian cystic lesions are frequent, with highly varied causes. They can
      be classified according to their location into intramedullary cystic lesions and
      extramedullary cystic lesions. In these two categories, they can then be
      regrouped according to the tissue from which they develop. MRI is the first
      choice examination for the study of the intracanal contents and the differential
      diagnosis between the various lesions.

PMID- 17541358
TI  - [Elastography of the breast: a prospective study of 122 lesions].
AB  - OBJECTIVE: To evaluate elastography in the characterization of breast nodules.
      MATERIAL AND METHODS: Elastography (Hitachi, 7.5- to 13-MHz probe; Ueno
      classification, scores 1-3=benign, 4-5=malignant) was evaluated in 125
      subclinical lesions in 114 patients. The results were compared to those of the
      ACR's BI-RADS sonography categories (benign=2 and 3, malignant=4 and 5) and to
      the results of the percutaneous samples taken and/or surgery (122 lesions
      evaluated, 59%<10 mm, 61 cancers, 61 benign lesions). RESULTS: There were three
      technical failures (2.4%). The elastography was in agreement with histology for
      101 lesions, with 13 false-negative results and eight false-positive results
      (sensitivity, 78.7%; specificity, 86.9%; PPV, 85.7%; NPV, 80.3%); versus
      agreement with the BI-RADS classification for 98 lesions with one false-negative
      result and 23 false-positive results (sensitivity, 98.4%; specificity, 47.5%;
      PPV, 65.2%; NPV, 96.7%). CONCLUSION: Elastography is a simple and rapid
      complementary method that can improve the specificity and the PPV of
      morphological imaging studies of breast nodules with a low level of suspicion (BI
      RADS categories 3 and 4a), which should decrease the rate of unnecessary benign
      biopsies.

PMID- 17541359
TI  - [Myositis ossificans circumscripta: the contribution of imaging].
AB  - OBJECTIVES: Illustrate the specific and nonspecific aspects of myositis
      ossificans circumscripta (MOC) in standard imaging, cross-sectional imaging
      (sonography, CT, and MRI), and bone scintigraphy. PATIENTS AND METHODS: Eight
      patients presenting with MOC (three men and five women) were explored using
      standard radiography (eight cases), sonography (seven cases), scintigraphy (four
      cases), CT (six cases), and MRI (four cases). RESULTS: Standard x-rays and
      sonography of the soft tissue showed a well-defined mass containing
      calcifications in 75% of the cases. The CT scan diagnosed MOC in four cases,
      showing calcified masses separated from the adjacent bone by a clear
      radiotransparent border or afferent peripheral tumoral calcifications highly
      suggestive of MOC. MRI was nonspecific. Bone scintigraphy showed hyperfixation in
      the four cases imaged. CONCLUSION: Standard x-rays were useful to demonstrate the
      calcifications of MOC and to identify their relation with the subjacent bone.
      Sonography and bone scintigraphy were interesting in monitoring the lesion's
      maturation. In addition to early detection of calcifications, CT can precisely
      localize the lesion before surgical ablation. MRI is a very sensitive technique
      in detecting small lesions at an early stage, but it is nonspecific and does not
      remove the necessity of biopsy to eliminate the possibility of a malignant
      disease.

PMID- 17541360
TI  - [The first campaign to evaluate interns in radiodiagnosis in 2005: national
      results].
AB  - Teaching cannot exist without evaluation for three main reasons: it is
      indispensable to know interns' skills in radiodiagnosis and medical imaging
      during their training; it is useful to encourage excellence in interns to
      stimulate their learning; and finally, it is indispensable to provide feedback to
      teaching personnel so as to modify or correct teaching techniques, modalities,
      and programs. In September 2005, 260 interns in training participated voluntarily
      in the first national evaluation campaign. We will attempt to delineate the main
      lines of this initial experience as well as its limitations.

PMID- 17541361
TI  - [Imaging of serious visceral forms of mucormycosis in five immunodepressed
      patients].
AB  - OBJECTIVES: Show the contribution of imaging to the diagnosis and follow-up of
      serious mucormycosis in immunodepressed patients. MATERIALS AND METHODS:
      Retrospective analysis of the 5-year radiological data in serious forms of
      mucormycosis occurring in patients with bone marrow allografts who are in
      refractory chronic graft-versus-host disease after bone marrow transplantation
      from 2002 to 2005. The positive diagnosis was bacteriologically and
      pathologically positive in all cases. RESULTS: This study involved three patients
      with isolated pulmonary involvement and two cases of disseminated mucormycosis.
      Areas of pulmonary condensations were found in all cases, one of whom had a low
      attenuation zone and parenchymal nodules. The kidney, liver, and spleen lesions
      were clearly limited, hypoechogenic, hypodense, and homogenous with no peripheral
      contrast material uptake. There was thyroid involvement in the form of
      hypoechogenic nodules. Rapid growth of the lesions was observed on follow-up CT
      (n=3) and despite surgical treatment (n=2) and intensive medical management, all
      cases ended in death. CONCLUSION: Mucormycosis is an integral part of the
      differential diagnosis of infectious syndromes in immunodepressed patients during
      the period after bone marrow transplantation. Imaging can assist in the diagnosis
      but pathological confirmation remains indispensable.

PMID- 17541362
TI  - [Bilateral orbital extension of breast cancer metastasis].

PMID- 17541363
TI  - [Portal dissection during TIPS placement].

PMID- 17541364
TI  - [CT-enteroclysis diagnosis of the cause of small-bowel hemorrhage].

PMID- 17541365
TI  - [An unusual cause of acute abdomen in a child: spontaneous rupture of a
      choledochal cyst].

PMID- 17541366
TI  - [How I perform a breast MRI].

PMID- 17541367
TI  - [Answer to April e-Quid].

PMID- 17541370
TI  - [Imaging of traumatic injuries of the shoulder].
AB  - The goals of this article are: 1) to review the different radiographic
      projections commonly used at the time of initial imaging evaluation of patients
      presenting with traumatic injuries of the shoulder; 2) to review the indications
      and findings of cross-sectional imaging modalities in the assessment of shoulder
      trauma; 3) to recognize the main anatomical lesions secondary to traumatic
      injuries of the shoulder.

PMID- 17541371
TI  - [Imaging of traumatic injuries of the elbow].
AB  - Traumatic injuries to the elbow may result in dislocations and/or fractures of
      the distal humerus or proximal radius or ulna. Multiple and associated lesions
      are common. Plain radiographs usually allow accurate diagnosis. These lesions may
      lead to joint stiffness with poor functional prognosis.

PMID- 17541372
TI  - [The diagnosis of recent scaphoid fractures: review of the literature].
AB  - Fractures of the scaphoid are the most common carpal fractures. A review of the
      literature indicates that the prevalence of the fracture in the case of clinical
      suspicion is less than 50%. A quality X-ray examination remains essential as an
      initial diagnostic tool in the evaluation of scaphoid fractures. Its sensitivity
      varies from 59 to 79%. Patients with negative X-rays present with about 18.7% of
      scaphoid fractures; 5% of bruised scaphoid; 13% of radius fractures and 7% of
      miscellaneous bone lesions. If not treated promptly, a scaphoid fracture may be
      compounded by non-union with associated risk factors such as avascular necrosis
      and osteoarthritis. Considering these risks, patients with suspected scaphoid
      fracture with normal X-rays, routinely undergo wrist immobilization until imaging
      confirms or denies the presence of fracture. Consequently, more than half of the
      patients undergo wrist immobilization needlessly. This may have a negative impact
      on their professional life and personal activities while representing a high
      medical cost. MRI is the imaging technique of choice for suspicious or negatice X
      rays. MDCT is less costly than MRI or bone scan, readily available and highly
      effective for trauma patients but is lacks accuracy and should be used with
      caution in this indication.

PMID- 17541373
TI  - [Imaging of traumatic injuries of the hip].
AB  - Traumatic injuries of the hip, mostly fractures of the proximal femur, are in
      constant progression. Though morbidity has decreased due to improved surgical and
      anesthesiologic techniques and postsurgical rehabilitation, mortality from hip
      fractures remains significant. Radiographs of the hip remain helpful, but MDCT
      and MRI have become indispensable tools. Findings on imaging studies must be well
      characterized to ensure rapid and cost-effective management. Difficult or cases
      with imaging features that are difficult to interpret or misleading will be
      presented to avoid incorrect interpretations that could lead to inadequate
      management of patients.

PMID- 17541374
TI  - [Imaging of traumatic injuries of the knee].
AB  - Traumatic injuries to the knee are frequent (road or sports related accidents,
      falls in elderly people). The Ottawa knee rules are applied and dictate the need
      for additional evaluation. Some fractures are adequately assessed on plain
      radiographs alone whereas other fractures (tibial plateau fracture) require
      additional evaluation with CT. Some fractures may be occult: the significance of
      lipohemarthrosis (indirect sign of intra-articular fracture on the lateral
      radiograph with horizontal beam) must be known. Benign appearing avulsion
      fractures suggest the presence of underlying capsuloligamentous injuries
      requiring further evaluation with MRI. The imaging work-up of sprains is usually
      negative. MRI may show areas of bone contusion that further the understanding of
      the mechanism of injury, predict and confirm the presence of capsuloligamentous
      injuries. Angiography is performed to detect popliteal artery injuries after knee
      dislocation which is associated with a risk of ischemia.

PMID- 17541375
TI  - [Imaging of traumatic injuries of the foot and ankle].
AB  - Traumatic injuries of the foot and ankle are frequent and constitute a true
      public health problem with over 6000 daily cases in France. The complex anatomy
      of this area and its association to other injuries in polytraumatized patients
      can lead to delayed diagnosis with worsened functional prognosis. Accurate
      diagnosis relies on good knowledge of osseous and ligamentous lesions and their
      associations and sometimes requires the use of additional imaging techniques
      including US and CT.

PMID- 17541376
TI  - [How to read radiography of the traumatic spine?].
AB  - In this paper, the imaging features of traumatic injuries of the spine in an
      emergency department will be reviewed. Three themes are discussed. 1) Review of
      current indications for additional imaging work-up. Conventional radiographs are
      not always mandatory, especially at the cervical level since validated criteria
      are available from the literature. The low sensitivity of conventional
      radiographs often requires additional imaging by CT (bone lesions) or MRI (disk
      and ligamentous lesions). The degree of urgency in scheduling these different
      examinations will be defined by the clinical setting and risk level
      (low/intermediate/high) of the injury. 2) Review of imaging features associated
      with stable and unstable lesions. The analysis of conventional radiographs is
      based on biomechanical concepts. The features of the main lesions will be
      illustrated by clinical cases and diagrams. 3) Review of key points that must
      urgently be transmitted to clinicians. The preliminary radiology report is an
      essential document for the management of patients with traumatic injury to the
      spine. It will have an impact on the type of immediate management (medical,
      orthopedic or surgical). A final report validating the initial interpretation
      should, of course, soon follow.

PMID- 17541377
TI  - Sitagliptin/metformin (Janumet) for type 2 diabetes.

PMID- 17541379
TI  - MoviPrep: a new bowel prep for colonoscopy.

PMID- 17541381
TI  - Report from london.

PMID- 17541383
TI  - Metabolic syndrome and ambulatory arterial stiffness index in non-diabetic
      patients with primary hypertension.
AB  - Increased arterial stiffness and the presence of metabolic syndrome (MS) have
      been shown to predict cardiovascular events in patients with primary
      hypertension. We investigated the relationship between a recently proposed index
      of arterial stiffness derived from ambulatory blood pressure (BP) monitoring and
      MS in 156 untreated, non-diabetic patients with primary hypertension. Ambulatory
      arterial stiffness index (AASI) was defined as 1 minus the regression slope of
      diastolic over systolic BP readings obtained from 24-h recordings. A modified
      National Cholesterol Education Program definition for MS was used, with body mass
      index replacing waist circumference. The prevalence of MS was 23%. Patients with
      MS were more frequently male (0.0291) and had increased serum uric acid
      (P=0.0005), high-sensitivity C-reactive protein (P=0.0259), as well as total and
      low-density lipoprotein (LDL)-cholesterol (P=0.0374 and P=0.0350, respectively)
      as compared to those without MS. After adjusting for these confounders, the
      association between AASI and the presence of MS was statistically significant
      (P=0.0257). Moreover, the prevalence of increased AASI (upper tertile, that is
      >or=0.550) was greater in patients with MS (P=0.0156). After adjusting for age
      and 24-h mean BP, the presence of MS entailed a more than twofold greater risk
      for increased AASI (0.0280). MS is associated with increased AASI in non-diabetic
      patients with primary hypertension. These data support the role of this new index
      of arterial stiffness as a marker of risk and help to explain the high
      cardiovascular morbidity and mortality that is observed in hypertensive patients
      with MS.

PMID- 17541384
TI  - Serum uric acid, the endothelium and hypertension: an association revisited.

PMID- 17541385
TI  - Metabolic syndrome in subjects with white-coat hypertension: impact on left
      ventricular structure and function.
AB  - Some reports have suggested that white-coat hypertension (WCH) is associated with
      some features of the metabolic syndrome (MetS). These metabolic disturbances,
      instead of WCH per se, may potentially explain the greater extent of end-organ
      damage sometimes observed in WCH subjects (WCHs) when compared to normotensive
      individuals (NTs). The aim of the present cross-sectional study was to compare
      left ventricular (LV) structure and function in three groups of subjects: WCHs
      with MetS, WCHs without MetS and NTs. A total of 145 WCHs, 35% of whom had MetS,
      were enrolled. As controls, 35 NTs were also studied. In all subjects, routine
      blood chemistry, echocardiographic examination and 24-h ambulatory blood pressure
      monitoring were performed. When compared with WCHs without MetS, those with MetS
      showed higher LV mass indexed by height elevated by a power of 2.7 (LVMH(2.7))
      (49.6+/-14.8 vs 38.9+/-9.8 g/m(2.7); P<0.0001). The same parameter was greater in
      WCHs without MetS than in NTs (32+/-8 g/m(2.7); P=0.004). Moreover, the E-wave
      deceleration time was longer in WCHs with MetS than in those without it (236.2+/
      66.4 vs 200.5+/-30.8 ms; P<0.0001). The relationship of MetS with LVMH(2.7) was
      confirmed in multivariate regression models. Our results seem to suggest that
      MetS may have a deleterious influence on LV structure and function in WCH.
      However, WCH, being associated with an increased LV mass, also in subjects
      without MetS, may not be considered as an innocuous phenomenon.

PMID- 17541386
TI  - Biofeedback treatment of prehypertension: analyses of efficacy, heart rate
      variability and EEG approximate entropy.

PMID- 17541387
TI  - Pulse pressure determines left atrial enlargement in non-dipper patients with
      never-treated essential hypertension.

PMID- 17541388
TI  - War veterans of Nepal and their blood pressure status: a population-based
      comparative study.

PMID- 17541389
TI  - Renin inhibition: the holy grail of renin-angiotensin system blockade?

PMID- 17541390
TI  - A comparison of the tolerability of the direct renin inhibitor aliskiren and
      lisinopril in patients with severe hypertension.
AB  - Patients with severe hypertension (>180/110 mm Hg) require large blood pressure
      (BP) reductions to reach recommended treatment goals (<140/90 mm Hg) and usually
      require combination therapy to do so. This 8-week, multicenter, randomized,
      double-blind, parallel-group study compared the tolerability and antihypertensive
      efficacy of the novel direct renin inhibitor aliskiren with the angiotensin
      converting enzyme inhibitor lisinopril in patients with severe hypertension (mean
      sitting diastolic blood pressure (msDBP)>or=105 mm Hg and <120 mm Hg). In all,
      183 patients were randomized (2:1) to aliskiren 150 mg (n=125) or lisinopril 20
      mg (n=58) with dose titration (to aliskiren 300 mg or lisinopril 40 mg) and
      subsequent addition of hydrochlorothiazide (HCTZ) if additional BP control was
      required. Aliskiren-based treatment (ALI) was similar to lisinopril-based
      treatment (LIS) with respect to the proportion of patients reporting an adverse
      event (AE; ALI 32.8%; LIS 29.3%) or discontinuing treatment due to AEs (ALI 3.2%;
      LIS 3.4%). The most frequently reported AEs in both groups were headache,
      nasopharyngitis and dizziness. At end point, ALI showed similar mean reductions
      from baseline to LIS in msDBP (ALI -18.5 mm Hg vs LIS -20.1 mm Hg; mean treatment
      difference 1.7 mm Hg (95% confidence interval (CI) -1.0, 4.4)) and mean sitting
      systolic blood pressure (ALI -20.0 mm Hg vs LIS -22.3 mm Hg; mean treatment
      difference 2.8 mm Hg (95% CI -1.7, 7.4)). Responder rates (msDBP<90 mm Hg and/or
      reduction from baseline>or=10 mm Hg) were 81.5% with ALI and 87.9% with LIS.
      Approximately half of patients required the addition of HCTZ to achieve BP
      control (ALI 53.6%; LIS 44.8%). In conclusion, ALI alone, or in combination with
      HCTZ, exhibits similar tolerability and antihypertensive efficacy to LIS alone,
      or in combination with HCTZ, in patients with severe hypertension.

PMID- 17541391
TI  - Serum uric acid is associated with microvascular function in hypertensive
      individuals.
AB  - We investigated the relationship of serum uric acid (UA) with resting forearm
      blood flow (FBF), reactive hyperaemia (RH) and flow-mediated dilation (FMD) of
      the brachial artery in hypertensive adults (n=506, mean age 62 years, 59% women).
      UA was measured by a colorimetric method. FBF, RH and FMD were measured by
      brachial artery ultrasound. Regression analyses were used to assess whether UA
      was associated with FBF, RH and FMD before and after adjustment for age, sex,
      systolic BP, diabetes, total and high-density lipoprotein cholesterol, smoking,
      body mass index (BMI), C-reactive protein (CRP), serum creatinine, alcohol
      intake, statin and diuretic use and brachial artery diameter (BAD). UA was
      significantly associated with FBF (P<0.0001) and RH (P=0.0001) but not with FMD
      (P=0.43). After adjustment for the covariates listed above, higher UA level
      remained independently associated with a higher FBF (P=0.012) and lower RH
      (P=0.004). The independent predictors were as follows: (a) higher FBF: lower age,
      higher BMI, history of smoking, statin use, higher CRP, higher BAD and higher UA
      levels; (b) lower RH: higher BMI, diabetes and higher UA levels; (c) lower FMD:
      greater age, male sex, higher BMI, history of smoking, statin use and higher BAD.
      We conclude that in hypertensive individuals, higher UA levels are associated
      with higher resting FBF and lower RH, markers of microvascular function, but not
      with brachial artery FMD.

PMID- 17541392
TI  - Polymorphisms in the DNA ligase IV gene might influence the risk of acute
      lymphoblastic leukemia in children.

PMID- 17541393
TI  - Human erythroleukemia: is the two-hit model of mouse leukemogenesis valid in
      human disease?

PMID- 17541394
TI  - Transplantation of mesenchymal stem cells to enhance engraftment of hematopoietic
      stem cells.
AB  - Seven patients underwent treatment with mesenchymal stem cells (MSCs), together
      with allogeneic hematopoietic stem cell transplantation (HSCT). MSCs were given
      to three patients for graft failure and four patients were included in a pilot
      study. HSCT donors were three human leukocyte antigen (HLA)-identical siblings,
      three unrelated donors and one cord blood unit. The conditioning was
      myeloablative in four patients and reduced in three patients. MSC donors were HLA
      identical siblings in three cases and haploidentical in four cases. Neutrophil
      counts >0.5 x 10(9)/l was reached at a median of 12 (range 10-28) days. Platelet
      counts >30 x 10(9)/l was achieved at a median of 12 (8-36) days. Acute graft
      versus-host disease (GVHD) grade 0-I was seen in five patients. Two patients
      developed grade II, which in one patient evolved into chronic GVHD. One severe
      combined immunodeficiency (SCID) patient died of aspergillosis, the others are
      alive and well. One patient, diagnosed with aplastic anemia had graft failure
      after her first transplantation and severe Henoch-Schonlein Purpura (HSP). After
      retransplantation of MSCs and HSCs, she recovered from both the HSP and aplasia.
      Thus, co-transplantation of MSC resulted in fast engraftment of absolute
      neutrophil count (ANC) and platelets and 100% donor chimerism, even in three
      patients regrafted for graft failure/rejection.

PMID- 17541395
TI  - A new partner gene fused to ABL1 in a t(1;9)(q24;q34)-associated B-cell acute
      lymphoblastic leukemia.

PMID- 17541396
TI  - BCR-ABL(T315I) transcript disappearance in an imatinib-resistant CML patient
      treated with homoharringtonine: a new therapeutic challenge?

PMID- 17541397
TI  - The hunt for cancer-initiating cells: a history stemming from leukemia.
AB  - Conventional cancer therapies are plagued by disease relapses due to incomplete
      eradication of cancer-initiating cells. Evidence for cancer-initiating cells
      originally arose from studies in hematology and leukemia. Lessons learned from
      hematopoietic stem cells laid the bedrock for understanding how leukemic cells
      self-renew and remain in immature states. Decades later, leukemia-initiating cell
      techniques are now being applied to the field of solid tumors such as brain,
      breast, bone, colon, pancreas, lung and prostate cancer, with several cancer
      initiating cell efforts led by hematologists. Different isolation techniques
      enriching for primitive cancer-initiating cells have been developed and are
      described in this review. Although the concept of cancer-initiating cells arose
      from studies in normal tissue stem cells, differences exist between neoplastic
      initiating clones and their normal counterparts. Several efforts have uncovered
      aberrant molecular pathways and niche interactions unique to cancer-initiating
      cells. Efforts to exploit these pathways and interactions could ultimately lead
      to complete eradication of cancers.

PMID- 17541398
TI  - Chromosomal translocations independently predict treatment failure, treatment
      free survival and overall survival in B-cell chronic lymphocytic leukemia
      patients treated with cladribine.
AB  - Chromosomal translocations represent an important prognostic indicator in B-cell
      chronic lymphocytic leukemia (B-CLL). However, their value had been neither
      determined in homogeneously treated patients nor compared to that of IgV(H)
      mutational status. Sixty-five B-CLL patients were investigated using
      cytogenetics, interphase fluorescence in situ hybridization (FISH), analysis of
      IgV(H) and of TP53 mutational status before treatment with 2-chloro-2'
      deoxyadenosine (CdA). Translocations (n=45) were detected in 42% of the patients,
      including both balanced (n=12) and unbalanced (n=33) types. IgV(H) was mutated in
      43% of the patients. Patients with translocations were more heavily pretreated
      (P=0.05), presented with more complex karyotypes (P<0.001), 17p abnormalities and
      TP53 mutations, and had a higher failure rate (59 vs 21% in patients without
      translocations, P=0.004). Patients with unbalanced translocations displayed a
      shorter median treatment-free survival (TFS, 6.9 vs 35.9 months, log rank 22.72,
      P<0.001) and overall survival (OS, 13.0 vs 68.0 months, log rank 16.51, P<0.001),
      as compared to patients without translocation. In multivariate analysis,
      unbalanced translocations were independently associated with therapeutic failure,
      short TFS and short OS. IgV(H) mutational status was independently associated
      with risk of failure and TFS, but not OS. In B-CLL patients treated with CdA,
      translocations are strong predictors of outcome.

PMID- 17541399
TI  - Donor-derived mucosal epithelial cells after human hematopoietic cell
      transplantation are not derived from the CD34-positive fraction of the graft.

PMID- 17541400
TI  - EBV-positive lymphoproliferative disease with medullary, splenic and hepatic
      infiltration after imatinib mesylate therapy for chronic myeloid leukemia.

PMID- 17541401
TI  - Identification of two distinct MYC breakpoint clusters and their association with
      various IGH breakpoint regions in the t(8;14) translocations in sporadic Burkitt
      lymphoma.
AB  - The chromosomal translocation t(8;14) is the hallmark of Burkitt's-lymphoma (BL)
      and fuses the proto-oncogene c-MYC to the IGH locus. We analyzed the genomic
      structure of MYC/IGH fusions derived from a large series of 78 patients with
      t(8;14) and asked (i) whether distinct breakpoint clusters exist within the MYC
      gene and (ii) whether any pairwise association between particular IGH and MYC
      breakpoints exist. Identification of such associations will help elucidate the
      etiology of the breaks on the MYC locus. Scan statistic analyses revealed two
      distinct, but large clusters within c-MYC containing 60/78 (77%) of the
      breakpoints. Clusters 1 and 2 were 560 and 779 bp in length within a 4555 bp
      breakpoint cluster region. Breaks within IGH switch mu and joining region did not
      differ with respect to their corresponding MYC breakpoints. However, there was a
      highly significant correlation between breakpoints 5' of MYC cluster 1 and
      fusions to IGH switch gamma region and breakpoints downstream of MYC cluster 2
      and fusions to IGH switch alpha region (chi(2)-test: P<0.005). Chromatin changes
      governing choice of IGH-Fc region recombination may parallel changes in the MYC
      gene 5' region chromatin leading to some degree of coordinated ontological
      specificity in breakpoint location.

PMID- 17541402
TI  - TG101209, a small molecule JAK2-selective kinase inhibitor potently inhibits
      myeloproliferative disorder-associated JAK2V617F and MPLW515L/K mutations.
AB  - JAK2V617F and MPLW515L/K represent recently identified mutations in
      myeloproliferative disorders (MPD) that cause dysregulated JAK-STAT signaling,
      which is implicated in MPD pathogenesis. We developed TG101209, an orally
      bioavailable small molecule that potently inhibits JAK2 (IC(50)=6 nM), FLT3
      (IC(50)=25 nM) and RET (IC(50)=17 nM) kinases, with significantly less activity
      against other tyrosine kinases including JAK3 (IC(50)=169 nM). TG101209 inhibited
      growth of Ba/F3 cells expressing JAK2V617F or MPLW515L mutations with an IC(50)
      of approximately 200 nM. In a human JAK2V617F-expressing acute myeloid leukemia
      cell line, TG101209-induced cell cycle arrest and apoptosis, and inhibited
      phosphorylation of JAK2V617F, STAT5 and STAT3. Therapeutic efficacy of TG101209
      was demonstrated in a nude mouse model. Furthermore, TG101209 suppressed growth
      of hematopoietic colonies from primary progenitor cells harboring JAK2V617F or
      MPL515 mutations.

PMID- 17541403
TI  - Truncations of amphiphysin I by calpain inhibit vesicle endocytosis during neural
      hyperexcitation.
AB  - Under normal physiological conditions, synaptic vesicle endocytosis is regulated
      by phosphorylation and Ca(2+)-dependent dephosphorylation of endocytic proteins
      such as amphiphysin and dynamin. To investigate the regulatory mechanisms that
      may occur under the conditions of excessive presynaptic Ca(2+) influx observed
      preceding neural hyperexcitation, we examined hippocampal slices following high
      potassium or high-frequency electrical stimulation (HFS). In both cases, three
      truncated forms of amphiphysin I resulted from cleavage by the protease calpain.
      In vitro, the binding of truncated amphiphysin I to dynamin I and
      copolymerization into rings with dynamin I were inhibited, but its interaction
      with liposomes was not affected. Moreover, overexpression of the truncated form
      of amphiphysin I inhibited endocytosis of transferrin and synaptic vesicles.
      Inhibiting calpain prevented HFS-induced depression of presynaptic transmission.
      Finally, calpain-dependent amphiphysin I cleavage attenuated kainate-induced
      seizures. These results suggest that calpain-dependent cleavage of amphiphysin I
      inhibits synaptic vesicle endocytosis during neural hyperexcitation and
      demonstrate a novel post-translational regulation of endocytosis.

PMID- 17541404
TI  - Interactions between human BRCA2 protein and the meiosis-specific recombinase
      DMC1.
AB  - Germline mutations in BRCA2 predispose to hereditary breast cancers. BRCA2
      protein regulates recombinational repair by interaction with RAD51 via a series
      of degenerate BRC repeat motifs encoded by exon 11 (BRCA2(996-2113)), and an
      unrelated C-terminal domain (BRCA2(3265-3330)). BRCA2 is also required for
      meiotic recombination. Here, we show that human BRCA2 binds the meiosis-specific
      recombinase DMC1 and define the primary DMC1 interaction site to a 26 amino-acid
      region (BRCA2(2386-2411)). This region is highly conserved in BRCA2 proteins from
      a variety of mammalian species, but is absent in BRCA2 from Arabidopsis thaliana,
      Caenorhabditis elegans, and other eukaryotes. We demonstrate the critical
      importance of Phe2406, Pro2408, and Pro2409 at the conserved motif
      (2404)KVFVPPFK(2411). This interaction domain, defined as the PhePP motif,
      promotes specific interactions between BRCA2 and DMC1, but not with RAD51. Thus,
      the RAD51 and DMC1 interaction domains on BRCA2 are distinct from each other,
      allowing coordinated interactions of the two recombinases with BRCA2 at meiosis.
      These results lead us to suggest that BRCA2 is a universal regulator of
      RAD51/DMC1 recombinase actions.

PMID- 17541405
TI  - Increased tumor cell dissemination and cellular senescence in the absence of
      beta1-integrin function.
AB  - Integrins are transmembrane receptors that bind extracellular matrix proteins and
      enable cell adhesion and cytoskeletal organization, as well as transduction of
      signals into cells, to promote various aspects of cellular behavior, such as
      proliferation or survival. Integrins participate in many aspects of tumor
      biology. Here, we have employed the Rip1Tag2 transgenic mouse model of pancreatic
      beta cell carcinogenesis to investigate the role of beta(1)-integrin in tumor
      progression. Specific ablation of beta(1)-integrin function in pancreatic beta
      cells resulted in a defect in sorting between insulin-expressing beta cells and
      glucagon-expressing alpha cells in islets of Langerhans. Ablation of beta(1)
      integrin in beta tumor cells of Rip1Tag2 mice led to the dissemination of tumor
      cell emboli into lymphatic blood vessels in the absence of ongoing
      lymphangiogenesis. Yet, disseminating beta(1)-integrin-deficient beta tumor cells
      did not elicit metastasis. Rather, primary tumor growth was significantly
      impaired by reduced tumor cell proliferation and the acquisition of cellular
      senescence by beta(1)-integrin-deficient beta tumor cells. The results indicate a
      critical role of beta(1)-integrin function in mediating metastatic dissemination
      and preventing tumor cell senescence.

PMID- 17541406
TI  - Profilin2 contributes to synaptic vesicle exocytosis, neuronal excitability, and
      novelty-seeking behavior.
AB  - Profilins are actin binding proteins essential for regulating cytoskeletal
      dynamics, however, their function in the mammalian nervous system is unknown.
      Here, we provide evidence that in mouse brain profilin1 and profilin2 have
      distinct roles in regulating synaptic actin polymerization with profilin2
      preferring a WAVE-complex-mediated pathway. Mice lacking profilin2 show a block
      in synaptic actin polymerization in response to depolarization, which is
      accompanied by increased synaptic excitability of glutamatergic neurons due to
      higher vesicle exocytosis. These alterations in neurotransmitter release
      correlate with a hyperactivation of the striatum and enhanced novelty-seeking
      behavior in profilin2 mutant mice. Our results highlight a novel, profilin2
      dependent pathway, regulating synaptic physiology, neuronal excitability, and
      complex behavior.

PMID- 17541407
TI  - POU-V factors antagonize maternal VegT activity and beta-Catenin signaling in
      Xenopus embryos.
AB  - VegT and beta-Catenin are key players in the hierarchy of factors that are
      required for induction and patterning of mesendoderm in Xenopus embryogenesis. By
      descending the genetic cascades, cells lose their pluripotent status and are
      determined to differentiate into distinct tissues. Mammalian Oct-3/4, a POU
      factor of subclass V (POU-V), is required for the maintenance of pluripotency of
      embryonic stem cells. However, its molecular function within the early embryo is
      yet poorly understood. We here show that the two maternal Xenopus POU-V factors,
      Oct-60 and Oct-25, inhibit transcription of genes activated by VegT and beta
      Catenin. Maternal POU-V factors and maternal VegT show an opposite distribution
      along the animal/vegetal axis. Oct-25, VegT and Tcf3 interact with each other and
      form repression complexes on promoters of VegT and beta-Catenin target genes. We
      suggest that POU-V factors antagonize primary inducers to allow germ layer
      specification in a temporally and spatially coordinated manner.

PMID- 17541408
TI  - Ferroxidase activity is required for the stability of cell surface ferroportin in
      cells expressing GPI-ceruloplasmin.
AB  - Ferroportin (Fpn), a ferrous iron Fe(II) transporter responsible for the entry of
      iron into plasma, is regulated post-translationally through internalization and
      degradation following binding of the hormone hepcidin. Cellular iron export is
      impaired in mice and humans with aceruloplasminemia, an iron overload disease due
      to mutations in the ferroxidase ceruloplasmin (Cp). In the absence of Cp Fpn is
      rapidly internalized and degraded. Depletion of extracellular Fe(II) by the yeast
      ferroxidase Fet3p or iron chelators can maintain cell surface Fpn in the absence
      of Cp. Iron remains bound to Fpn in the absence of multicopper oxidases. Fpn with
      bound iron is recognized by a ubiquitin ligase, which ubiquitinates Fpn on lysine
      253. Mutation of lysine 253 to alanine prevents ubiquitination and maintains Fpn
      iron on cell surface in the absence of ferroxidase activity. The requirement for
      a ferroxidase to maintain iron transport activity represents a new mechanism of
      regulating cellular iron export, a new function for Cp and an explanation for
      brain iron overload in patients with aceruloplasminemia.

PMID- 17541409
TI  - Rice OsHKT2;1 transporter mediates large Na+ influx component into K+-starved
      roots for growth.
AB  - Excessive accumulation of sodium in plants causes toxicity. No mutation that
      greatly diminishes sodium (Na+) influx into plant roots has been isolated. The
      OsHKT2;1 (previously named OsHKT1) transporter from rice functions as a
      relatively Na+-selective transporter in heterologous expression systems, but the
      in vivo function of OsHKT2;1 remains unknown. Here, we analyzed transposon
      insertion rice lines disrupted in OsHKT2;1. Interestingly, three independent
      oshkt2;1-null alleles exhibited significantly reduced growth compared with wild
      type plants under low Na+ and K+ starvation conditions. The mutant alleles
      accumulated less Na+, but not less K+, in roots and shoots. OsHKT2;1 was mainly
      expressed in the cortex and endodermis of roots. (22)Na+ tracer influx
      experiments revealed that Na+ influx into oshkt2;1-null roots was dramatically
      reduced compared with wild-type plants. A rapid repression of OsHKT2;1-mediated
      Na+ influx and mRNA reduction were found when wild-type plants were exposed to 30
      mM NaCl. These analyses demonstrate that Na+ can enhance growth of rice under K+
      starvation conditions, and that OsHKT2;1 is the central transporter for
      nutritional Na+ uptake into K+-starved rice roots.

PMID- 17541410
TI  - Biologistes sans frontieres.
AB  - Junior researchers are encouraged to gain experience abroad, and for senior
      scientists, sabbaticals remain popular. France has taken the next step in
      fostering international exchange, by supporting long-term collaborations with
      foreign laboratories and by creating research units abroad.

PMID- 17541412
TI  - PA promoted to manager.

PMID- 17541413
TI  - Coding RNAs: separating the grain from the chaff.

PMID- 17541414
TI  - Anchoring microtubules at the spindle poles.

PMID- 17541415
TI  - Caspase-14 and epidermis maturation.

PMID- 17541416
TI  - Who, where, how many?

PMID- 17541417
TI  - Interfering with disease: a progress report on siRNA-based therapeutics.
AB  - RNA interference (RNAi) quietly crept into biological research in the 1990s when
      unexpected gene-silencing phenomena in plants and flatworms first perplexed
      scientists. Following the demonstration of RNAi in mammalian cells in 2001, it
      was quickly realized that this highly specific mechanism of sequence-specific
      gene silencing might be harnessed to develop a new class of drugs that interfere
      with disease-causing or disease-promoting genes. Here we discuss the
      considerations that go into developing RNAi-based therapeutics starting from in
      vitro lead design and identification, to in vivo pre-clinical drug delivery and
      testing. We conclude by reviewing the latest clinical experience with RNAi
      therapeutics.

PMID- 17541418
TI  - Microenvironmental regulation of biomacromolecular therapies.
AB  - There is currently great interest in molecular therapies to treat various
      diseases, and this has prompted extensive efforts to achieve target-specific and
      controlled delivery of bioactive macromolecules (for example, proteins,
      antibodies, DNA and small interfering RNA) through the design of smart drug
      carriers. By contrast, the influence of the microenvironment in which the target
      cell resides and the effect it might have on the success of biomacromolecular
      therapies has been under-appreciated. The extracellular matrix (ECM) component of
      the cellular niche may be particularly important, as many diseases and injury
      disrupt the normal ECM architecture, the cell adhesion to ECM, and the subsequent
      cellular activities. This Review will discuss the importance of the ECM and the
      ECM-cell interactions on the cell response to bioactive macromolecules, and
      suggest how this information could lead to new criteria for the design of novel
      drug delivery systems.

PMID- 17541419
TI  - Untangling tau hyperphosphorylation in drug design for neurodegenerative
      diseases.
AB  - Aggregation of hyperphosphorylated tau is one of the characteristic
      neuropathological lesions of Alzheimer's disease and other neurodegenerative
      disorders. Pharmacological modulation of tau hyperphosphorylation might represent
      a valid and feasible therapeutic strategy for such disorders. Here, we consider
      recent evidence supporting the validity of the three most relevant kinases
      affecting tau hyperphosphorylation - GSK3beta, CDK5 and ERK2 - as drug targets
      and describe progress in the design of inhibitors for these kinases.

PMID- 17541420
TI  - Matrix metalloproteinase inhibitors as therapy for inflammatory and vascular
      diseases.
AB  - Matrix metalloproteinases (MMPs) have outgrown the field of extracellular-matrix
      biology and have progressed towards being important regulatory molecules in
      cancer and inflammation. This rise in status was accompanied by the development
      of various classes of inhibitors. Although clinical trials with synthetic
      inhibitors for the treatment of cancer were disappointing, recent data indicate
      that the use of selective inhibitors might lead to new therapies for acute and
      chronic inflammatory and vascular diseases. In this Review, we compare the major
      classes of MMP inhibitors and advocate that future drug discovery should be based
      on crucial insights into the differential roles of specific MMPs in
      pathophysiology obtained with animal models, including knockout studies.

PMID- 17541421
TI  - Radioresponsive tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)
      gene therapy for malignant brain tumors.
AB  - Patients with malignant gliomas have a very poor prognosis. To explore a novel
      and more effective approach for the treatment of malignant gliomas, a strategy
      that combined tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)
      gene therapy and radiation treatment (RT) was designed in this study. Plasmid pE4
      GFP was constructed by including the radioinducible early growth response gene 1
      (Egr-1) promoter, and it yielded the best response with fractionated RT. Plasmid
      pE4-TRAIL was constructed by including the Egr-1 promoter and evaluated using
      U251 and U87 glioma cells. In the assay of apoptosis and killing activities, pE4
      TRAIL exhibited radioresponse. pE4-TRAIL combined with RT is capable of inducing
      cell death synergistically. The expression of TRAIL death receptors was
      evaluated; which may be influenced by RT. Glioma cells with wild-type p53 showed
      upregulated expression of death receptors, and more synergistic effects on
      killing activities are expected. pE4-TRAIL was transfected into the subcutaneous
      U251 glioma cells in nude mice by the in vivo electroporation method. In the mice
      treated with pE4-TRAIL and RT, apoptotic cells were detected in pathological
      sections, and a significant difference of tumor volumes was observed when
      compared with the other groups (P<0.001). Our results indicate that
      radioresponsive gene therapy may have great potential as a novel therapy because
      this therapeutic system can be spatially or temporally controlled by exogenous RT
      and provides specificity and safety.

PMID- 17541422
TI  - RNAi-mediated knockdown of target genes: a promising strategy for pancreatic
      cancer research.
AB  - Pancreatic cancer is one of the most aggressive malignancies with a very poor
      prognosis, partially due to its very low accessibility to resection and
      resistance to chemoradiotherapy. As such, it is reasonable to find more
      effective, specific therapies and the related therapeutic targets. The
      identification of certain genes contributing to the tumorigenesis and poor
      prognosis provides the specific targets for efficient silencing by RNA
      interference (RNAi). As a powerful tool to suppress gene expression in mammalian
      cells, RNAi can be directed against pancreatic cancer through various pathways,
      including the inhibition of overexpressed oncogenes, suppression of tumor growth,
      metastasis and enhancement of apoptosis. In combination with chemoradiotherapy
      agents, RNAi can also attenuate the chemoradiation resistance of pancreatic
      cancer. In addition, RNAi has been used to define the 'loss of function' of
      endogenous genes in pancreatic cancer. This review provides a brief introduction
      to recent developments of RNAi applications in pancreatic cancer studies and
      suggestions for further exploration. It substantially demonstrates that RNAi
      holds a promising therapeutic potential as a future treatment for pancreatic
      cancer.

PMID- 17541423
TI  - Microglia used as vehicles for both inducible thymidine kinase gene therapy and
      MRI contrast agents for glioma therapy.
AB  - Microglia are phagocytic cells that are chemoattracted by brain tumors and can
      represent up to 70% of the tumor cell population. To get insight into gene
      therapy against glioma, we decided to take advantage of those microglia
      properties and to use those cells as vehicles to transport simultaneously a
      suicide gene (under the control of a heat-sensitive promoter) and contrast agents
      to localize them by magnetic resonance imaging before applying any therapeutic
      treatment. Thymidine kinase (TK) expression and its functionality after
      gancyclovir administration were investigated. After the heat shock (44 degrees C
      and 20 min), TK was expressed in 50% of the cells. However, after gancyclovir
      treatment, 90% of the cells died by apoptosis, showing an important bystander
      effect. Then, the cells were incubated with new lanthanide contrast agents to
      check both their potential toxicity and their MR properties. Results indicate
      that the nanoparticles did not induce any cell toxicity and yield a hypersignal
      on MR images at 4.7 T. These in vitro experiments indicate that microglia are
      good candidates as vectors in gene therapy against brain tumors. Finally,
      microglia containing gadolinium-grafted nanoparticles were injected in the close
      vicinity of C6 tumor, in a mouse. The hyperintensive signal obtained on in vivo
      images as well as its retention time show the potential of the novel contrast
      agents for cellular imaging.

PMID- 17541424
TI  - Proof concept for clinical justification of network mapping for personalized
      cancer therapeutics.
AB  - To identify signature targets associated with patient-specific cancer lesions
      based on tumor versus normal tissue differential protein and mRNA coexpression
      patterns for the purpose of synthesizing cancer-specific customized RNA
      interference knockdown therapeutics. Analysis of biopsied tissue involved two
      dimensional difference in-gel electrophoresis (2D-DIGE) analysis coupled with
      MALDI-TOF/TOF mass spectrometry for proteomic assessment. Standard microarray
      techniques were utilized for mRNA analysis. Priority was assigned to
      overexpressed protein targets with co-overexpressed genes with a high likelihood
      of functional nodal centrality in the cancer network as defined by the
      interactive databases BIND, HPRD and ResNet. HPLC-grade small interfering RNA
      (siRNA) duplexes were utilized to assess knockdown of target proteins in
      expressive cell lines as measured by western blot. Seven patients with metastatic
      cancer underwent biopsy. One patient (RW001) had biopsies from two disease sites
      10 months apart. Seven priority proteins were identified, one for each patient
      (RACK 1, Ras related nuclear protein, heat-shock 27 kDa protein 1, superoxide
      dismutase, enolase1, stathmin1 and cofilin1). Prioritized proteins in RW001 from
      the two disease sites over time were the same. We demonstrated >80% siRNA
      inhibition of RACK 1 and stathmin1 of inexpressive malignant cell lines with
      correlated cell kill. Identification of functionally relevant target gene
      fingerprints, unique to an individual's cancer, is feasible 'at the bedside' and
      can be utilized to synthesize siRNA knockdown therapeutics. Further animal safety
      testing followed by clinical study is recommended.

PMID- 17541425
TI  - Intracellular sortilin expression pattern regulates proNGF-induced naturally
      occurring cell death during development.

PMID- 17541426
TI  - NK cells at the interface between innate and adaptive immunity.
AB  - In recent years a novel concept has emerged indicating that the actual role of
      natural killer (NK) cells is not confined to the destruction of virus-infected
      cells or tumors. Indeed, different NK subsets exist that display major functional
      differences in their cytolytic activity, cytokine production and homing
      capabilities. In particular, CD56(high) CD16(-) NK cells that largely predominate
      in lymph nodes, have little cytolytic activity but release high levels of
      cytokines whereas CD56(low) CD16(+) NK cells that predominate in peripheral blood
      and inflamed tissues, display lower cytokine production, but potent cytotoxicity.
      The latter is characterized by granule polarization and exocytosis of various
      proteins including perforin and granzymes that mediate target cell killing. The
      recruitment of CD56(low) CD16(+) NK cells into inflamed peripheral tissues is
      orchestrated by various chemochines including the newly identified Chemerin. At
      these sites, NK cells, upon engagement of different triggering receptors become
      activated and upregulate their cytokine production and cytotoxicity after
      interaction with myeloid dendritic cells (DCs). Importantly, during this
      interaction NK cells also mediate the 'editing' of DCs undergoing maturation.
      This process appears to play a crucial role in shaping both innate and adaptive
      immune responses. Indeed, only DCs undergoing this NK-mediated quality control
      would become fully mature and capable of inducing priming of protective Th1
      responses.

PMID- 17541427
TI  - Mdm38 protein depletion causes loss of mitochondrial K+/H+ exchange activity,
      osmotic swelling and mitophagy.
AB  - Loss of the MDM38 gene product in yeast mitochondria results in a variety of
      phenotypic effects including reduced content of respiratory chain complexes,
      altered mitochondrial morphology and loss of mitochondrial K(+)/H(+) exchange
      activity resulting in osmotic swelling. By use of doxycycline-regulated shut-off
      of MDM38 gene expression, we show here that loss of K(+)/H(+) exchange activity
      and mitochondrial swelling are early events, associated with a reduction in
      membrane potential and fragmentation of the mitochondrial reticulum. Changes in
      the pattern of mitochondrially encoded proteins are likely to be secondary to the
      loss of K(+)/H(+) exchange activity. The use of a novel fluorescent biosensor
      directed to the mitochondrial matrix revealed that the loss of K(+)/H(+) exchange
      activity was immediately followed by morphological changes of mitochondria and
      vacuoles, the close association of these organelles and finally uptake of
      mitochondrial material by vacuoles. Nigericin, a K(+)/H(+) ionophore, fully
      prevented these effects of Mdm38p depletion. We conclude that osmotic swelling of
      mitochondria triggers selective mitochondrial autophagy or mitophagy.

PMID- 17541429
TI  - Positive regulation of ASK1-mediated c-Jun NH(2)-terminal kinase signaling
      pathway by the WD-repeat protein Gemin5.
AB  - Gemin5 is a 170-kDa WD-repeat-containing protein that was initially identified as
      a component of the survival of motor neurons (SMN) complex. We now show that
      Gemin5 facilitates the activation of apoptosis signal-regulating kinase 1 (ASK1)
      and downstream signaling. Gemin5 physically interacted with ASK1 as well as with
      the downstream kinases SEK1 and c-Jun NH(2)-terminal kinase (JNK1), and it
      potentiated the H(2)O(2)-induced activation of each of these kinases in intact
      cells. Moreover, Gemin5 promoted the binding of ASK1 to SEK1 and to JNK1, as well
      as the ASK1-induced activation of JNK1. In comparison, Gemin5 did not physically
      associate with MKK7, MKK3, MKK6, or p38. Furthermore, depletion of endogenous
      Gemin5 by RNA interference (RNAi) revealed that Gemin5 contributes to the
      activation of ASK1 and JNK1, and to apoptosis induced by H(2)O(2) and tumor
      necrosis factor-alpha (TNFalpha) in HeLa cells. Together, our results suggest
      that Gemin5 functions as a scaffold protein for the ASK1-JNK1 signaling module
      and thereby potentiates ASK1-mediated signaling events.

PMID- 17541428
TI  - Therapeutic window for melanoma treatment provided by selective effects of the
      proteasome on Bcl-2 proteins.
AB  - Melanoma cells depend on sustained proteasomal function for survival. However,
      bortezomib, the first proteasome inhibitor in clinical use, is not sufficient to
      improve the poor prognosis of metastatic melanoma patients. Since the proteasome
      is also expressed in all normal cell compartments, it is unclear how to enhance
      the efficacy of bortezomib without exacerbating secondary toxicities. Here, we
      present pharmacological and genetic analyses of mechanisms of resistance to
      proteasome inhibition. We focused on Bcl-2, Bcl-x(L) and Mcl-1 as main
      antiapoptotic factors associated with melanoma progression. Despite an efficient
      blockage of the proteasome, bortezomib could not counteract the intrinsically
      high levels of Bcl-2 and Bcl-x(L) in melanoma cells. Moreover, Mcl-1 was only
      downregulated at late time points after treatment. Based on these results, a
      combination treatment including (-)-gossypol, an inhibitor of Mcl-1/Bcl-2/Bcl
      x(L), was designed and proven effective in vivo. Using a specific RNA
      interference approach, the survival of bortezomib-treated melanoma cells was
      found to rely primarily on Mcl-1, and to a lesser extent on Bcl-x(L) (but not on
      Bcl-2). Importantly, neither Mcl-1 nor Bcl-x(L) inactivation affected the
      viability of normal melanocytes. This hierarchical requirement of Bcl-2 family
      members for the maintenance of normal and malignant cells offers a therapeutic
      window to overcome melanoma chemoresistance in a tumor cell-selective manner.

PMID- 17541431
TI  - A new era for French science?

PMID- 17541433
TI  - Plastic electronics: Remotely powered by printing.

PMID- 17541434
TI  - Biomimetic synthesis: Double-walled silica nanotubes.

PMID- 17541435
TI  - Spintronics: A nanomagnet oscillator.

PMID- 17541437
TI  - Material witness: Feel the force.

PMID- 17541436
TI  - Polyelectrolyte gels: Ionic partners split up.

PMID- 17541438
TI  - Ferromagnetic semiconductors: Ruled by a magnetic-rich minority.

PMID- 17541439
TI  - Nanoscale compositional mapping with gentle forces.
AB  - Microscopists have always pursued the development of an instrument that combines
      topography and materials properties analyses at the highest resolution. The
      measurement of the tiny amount of energy dissipated by a vibrating tip in the
      proximity of the sample surface has provided atomic force microscopes with a
      robust and versatile method to determine the morphology and the compositional
      variations of surfaces in their natural environment. Applications in biology,
      polymer science and microelectronics illustrate the potential of phase-imaging
      force microscopy for nanoscale analysis.

PMID- 17541440
TI  - Correlation of Helicobacter pylori virulence genotypes vacA and cagA with
      histological parameters of gastritis and patient's age.
AB  - The histological parameters of Helicobacter pylori (H. pylori) gastritis are
      dependent on the virulence factor profile of the microbe, which includes the
      cytotoxins vacA (vacuolating cytotoxin A) and cagA (cytotoxin-associated gene A)
      as well as the duration of infection. The virulence factor genotypes vacA and
      cagA were assessed by the line probe reverse hybridization assay INNO-LiPA and
      correlated with the histological parameters of H. pylori infection, in particular
      intestinal metaplasia (IM) as well as with the patient's age. A total of 120
      patients were analyzed; 47 patients with IM in the antrum and 73 control patients
      without this alteration. The vacA s1 cagA+ genotype (high virulence) correlated
      with the presence of antral IM, a more intense acute inflammation in both antrum
      and corpus and the formation of ulcer. The vacA m1 genotype (high virulence)
      correlated with a more intense acute inflammation in only the corpus as well as
      more prominent Russell bodies in the antrum. H. pylori strains with the vacA s2
      m2 cagA- genotype (low virulence) were rarely found in these conditions (all P
      <0.05). No correlation with the virulence status was found for the type and
      extent of IM, the intensity of chronic inflammation, the formation of lymphoid
      follicles and the microbial density. Furthermore, patients with IM were 7 years
      older than their counterparts without (P<0.05). Finally, there was a trend for
      more virulent vacA s1 m1 cagA+ strains to be found in younger individuals
      (P>0.05). The virulence genotype of the microbe is an important determinant for
      the severity of the gastritis and the formation of antral IM. Age is an
      additional factor for the development of IM.

PMID- 17541441
TI  - Predominance of the basal type and HER-2/neu type in brain metastasis from breast
      cancer.
AB  - Although breast cancer is the second most common cause of central nervous system
      (CNS) metastases with a notable increase of incidence, only few studies on brain
      metastasizing breast cancer are available. In this immunohistochemical and
      fluorescence in situ hybridization (FISH) study, metastases to the CNS (n=85) and
      primary breast cancers, with known involvement of the CNS (n=44) including paired
      primary and metastasized tumours (n=23), were investigated retrospectively for
      the expression of oestrogen- (ER) and progesterone- (PR) hormone receptors, Her
      2/neu, epidermal growth factor receptor (EGFR), Ki-67, and cytokeratins (CKs)
      5/14. The majority of brain metastases were steroid hormone receptor negative (ER
      66%, PR 82%) corresponding to the findings in primary tumours with known
      involvement of the CNS (68% ER-negative, 75% PR-negative). The frequency of HER
      2/neu-overexpressing or -amplified cancers was increased in both groups (34 and
      32%, respectively). EGFR expression was more frequent in metastases (41%) than in
      primary tumours (16%). The proportions of cases with a basal phenotype were 26
      and 30%, respectively. In paired primary tumours and metastases to the CNS,
      constancy of Her-2/neu status was observed in 87% of cases with only one sample
      turning Her-2/neu-negative and two samples acquiring overexpression/amplification
      in brain metastases. In contrast, steroid hormone receptors exhibited more
      frequently a loss of expression (17%) than a gain (9%) with 74% revealing a
      constant phenotype. We conclude that brain-metastasizing breast cancer belongs
      predominantly to the basal type or Her-2/neu type. Primary and metastatic tumours
      differ from each other only in a minority of cases, leading rather to a loss of
      steroid hormone receptors and to a gain of EGFR and Her-2/neu.

PMID- 17541442
TI  - Lymphoepithelioma-like carcinoma of the urinary tract: a clinicopathological
      study of 30 pure and mixed cases.
AB  - We studied 28 cases of lymphoepithelioma-like carcinoma of the bladder, one case
      in the renal pelvis, and one in the urethra. The mean age of the patients was
      67.6 years with 21 (70%) males. Seventeen cases (56.7%) were pure with the
      remaining mixed with other patterns of carcinoma, including invasive urothelial
      carcinoma (n=10), invasive adenocarcinoma (n=3), and squamous cell carcinoma
      (n=2). The surface demonstrated carcinoma in situ (CIS) in six cases, noninvasive
      high-grade papillary urothelial carcinoma in three cases, and in situ
      adenocarcinoma in one case. In 19/30 (66%) cases, there was a heavy lymphocytic
      infiltrate and in the remaining 11/30 (34%) cases a mixed inflammatory
      infiltrate. None of the 26 cases labeled for EBV-encoded RNA by in situ
      hybridization. Tumor stages at presentation were: seven cases T1 (23%); 14 cases
      T2 (47%); seven cases T3 (23%); and two cases T4 (7%). Treatment consisted of
      radical cystectomy in 13/30 cases (43%); partial cystectomy in 4/30 cases (13%);
      nephrectomy in one case (3%), and transurethral resection often followed by
      radiation or chemotherapy in 12/30 (40%) cases. The mean follow up for patients
      without progression was 31 months. Eight of 27 cases with follow-up (30%) cases
      had tumor recurrence, with seven patients having metastases. In cases treated
      with cystectomy, the 5-year actuarial recurrence-free risk was 59% (62 and 57%,
      for pure and mixed cases, respectively). Lymphoepithelioma-like carcinoma,
      whether in pure or mixed form, has a similar prognosis to ordinary urothelial
      carcinoma when treated by cystectomy. Of the three pure cases treated by
      chemotherapy, two were free of disease at 4 and 65 months and the third had
      recurrent disease at 17 months. Given the association of lymphoepithelioma-like
      carcinoma with urothelial carcinoma in 47% of our cases and its propensity for
      multifocality, partial cystectomy would typically be ill advised for
      lymphoepithelioma-like carcinoma.

PMID- 17541443
TI  - Moving ahead or falling behind?

PMID- 17541444
TI  - Do physicians follow evidence-based guidelines in the diagnostic work-up of IBS?

PMID- 17541445
TI  - Autoimmune pancreatitis.
AB  - Autoimmune pancreatitis is a rare systemic fibrotic inflammatory disorder that
      can affect organs such as the bile ducts, salivary glands, and retroperitoneal
      lymph nodes, in addition to the pancreas. Morphological characteristics of
      autoimmune pancreatitis include a diffusely enlarged 'sausage-shaped' pancreas
      and an irregularly narrowed duct of Wirsung. According to the revised Japan
      Pancreas Society criteria, the diagnosis of autoimmune pancreatitis requires that
      one or more secondary serologic or histologic criteria are also met: the presence
      of autoantibodies, elevated levels of gamma-globulins, IgG or IgG(4), a
      lymphoplasmacytic infiltrate, or pancreatic fibrosis. The presence in any
      affected organ of a lymphoplasmacytic inflammatory infiltrate containing greater
      than 10 IgG(4)-positive cells per high-power field is pathognomonic for
      autoimmune pancreatitis. Precise data on the incidence and prevalence of
      autoimmune pancreatitis are currently not available because most reports involve
      either limited patient series or resection specimen cohorts. New diagnostic tools
      and further studies of the underlying pathophysiology and prognosis of autoimmune
      pancreatitis are needed for adequate and effective treatment strategies to be
      developed. The most crucial issue when caring for patients with suspected
      autoimmune pancreatitis is to differentiate autoimmune pancreatitis from
      pancreatic carcinoma, because pancreatic carcinoma requires surgery, whereas
      autoimmune pancreatitis responds well to steroid treatment.

PMID- 17541446
TI  - Surgery insight: minimally invasive surgery for IBD.
AB  - The most frequently described laparoscopic operations for the management of
      patients with IBD are restorative proctocolectomy for ulcerative colitis and
      ileocolic resection for Crohn's disease. For patients with Crohn's disease, there
      is level 1b evidence that, in experienced hands, laparoscopic ileocolic resection
      enhances recovery and leads to a shorter hospital stay compared with conventional
      ileocolic resection. The demonstrated advantages of laparoscopic ileocolic
      resection with regard to cost and cosmesis, and the acceptable long-term results
      achieved (which are at least comparable to those achieved by conventional
      ileocolic resection) favor the use of laparoscopic ileocolic resection over
      conventional ileocolic resection in patients with ileocolic Crohn's disease. For
      patients with ulcerative colitis, the expected advantages of laparoscopic
      restorative proctocolectomy over conventional restorative proctocolectomy have
      yet to be clearly shown. Although there is a trend towards a reduced hospital
      stay (of only 1.6 days) when laparoscopic restorative proctocolectomy is
      performed, operating times are disproportionably prolonged. The most important
      argument for offering patients with IBD the chance to undergo a laparoscopic
      procedure, rather than conventional open surgery, is (particularly for women) the
      long-term superior cosmesis and body image it confers.

PMID- 17541447
TI  - Mechanisms of disease: the pathological basis of gastroparesis--a review of
      experimental and clinical studies.
AB  - The pathogenesis of gastroparesis is complicated and poorly understood. This lack
      of understanding remains a major impediment to the development of effective
      therapies for this condition. Most of the scientific information available on the
      pathogenesis of gastroparesis has been derived from experimental studies of
      diabetes in animals. These studies suggest that the disease process can affect
      nerves (particularly those producing nitric oxide, but also the vagus nerve),
      interstitial cells of Cajal and smooth muscle. By contrast, human data are
      sparse, outdated and generally inadequate for the validation of data obtained
      from experimental models. The available data do, however, suggest that multiple
      cellular targets are involved. In practice, though, symptoms seldom correlate
      with objective measures of gastric function and there is still a lot to learn
      about the pathophysiology of gastroparesis. Future studies should focus on
      understanding the molecular pathways that lead to gastric dysfunction, in animal
      models and in humans, and pave the way for the development of rational therapies.

PMID- 17541448
TI  - Granulomatous ileitis in a patient with ankylosing spondylitis.
AB  - BACKGROUND: A 21-year-old white male with a 3-year history of back pain presented
      with a 6-month history of weight loss (without significant gastrointestinal
      symptoms), lethargy and left hip pain, and diarrhea that had lasted 4 days.
      INVESTIGATIONS: Barium follow-through, upper and lower gastrointestinal endoscopy
      and biopsies, capsule enteroscopy, CT of the chest and abdomen, measurement of
      the concentration of fecal calprotectin, intestinal absorption permeability test
      and wireless capsule endoscopy. DIAGNOSIS: Ankylosing spondylitis associated with
      ileitis of spondylarthropathy. MANAGEMENT: Sulfasalazine and elemental diet,
      steroids, physiotherapy and bilateral hip replacement.

PMID- 17541450
TI  - Programmed Ribosomal Frameshifting Goes Beyond Viruses: Organisms from all three
      kingdoms use frameshifting to regulate gene expression, perhaps signaling a
      paradigm shift.

PMID- 17541449
TI  - Children's dietary reporting accuracy over multiple 24-hour recalls varies by
      body mass index category.
AB  - This secondary analysis investigated the influence of body mass index (BMI)
      category and sex on reporting accuracy during multiple 24-hour dietary recalls.
      On three occasions, each of 79 children (40 girls) was observed eating school
      meals and interviewed the next morning about the previous day's intake, with >=
      25 days between any two consecutive occasions for a child. Using age/sex BMI
      percentiles, we categorized 48 children as healthy weight (>= 5(th) percentile
      <85(th)), 14 as at risk of overweight (>= 85(th) percentile <95(th)), and 17 as
      overweight (>=95(th) percentile). A repeated-measures analysis was conducted for
      each of five outcomes (number of items observed eaten, number of items reported
      eaten, omission rate, intrusion rate, total inaccuracy). For items observed, BMI
      category x trial was marginally significant (P=0.079); over trials, this outcome
      was stable for healthy-weight children, decreased and stabilized for at-risk-of
      overweight children, and was stable and decreased for overweight children. This
      outcome was greatest for overweight children and least for healthy-weight
      children (P=0.015). For items reported, no significant effects were found. For
      omission rate (P=0.028) and intrusion rate (P=0.083), BMI category x trial was
      significant and marginally significant; over trials, both decreased for healthy
      weight children, decreased and stabilized for at-risk-of-overweight children, and
      increased and stabilized for overweight children. Total inaccuracy decreased
      slightly over trials (P=0.076); this outcome was greater for boys than for girls
      (P=0.049). Results suggest that children's dietary reporting accuracy over
      multiple recalls varies by BMI category. Validation studies with adequate samples
      for each BMI category, sex, and race are needed.

PMID- 17541451
TI  - Processing MALDI Mass Spectra to Improve Mass Spectral Direct Tissue Analysis.
AB  - Profiling and imaging biological specimens using MALDI mass spectrometry has
      significant potential to contribute to our understanding and diagnosis of
      disease. The technique is efficient and high-throughput providing a wealth of
      data about the biological state of the sample from a very simple and direct
      experiment. However, in order for these techniques to be put to use for clinical
      purposes, the approaches used to process and analyze the data must improve. This
      study examines some of the existing tools to baseline subtract, normalize, align,
      and remove spectral noise for MALDI data, comparing the advantages of each. A
      preferred workflow is presented that can be easily implemented for data in ASCII
      format. The advantages of using such an approach are discussed for both molecular
      profiling and imaging mass spectrometry.

PMID- 17541452
TI  - panhandling repertoires and routines for overcoming the nonperson treatment.
AB  - In this article, I present panhandling as a dynamic undertaking that requires
      conscious actions and purposeful modifications of self, performances, and
      emotions to gain the attention and interest of passersby. I show that describing
      and theorizing panhandling in terms of dramaturgical routines is useful in
      understanding the interactions and exchanges that constitute panhandling. In
      addition, repertoires rightly portray panhandlers as agents engaging the social
      world rather than as passive social types. From this perspective, sidewalks serve
      as stages on which panhandlers confront and overcome various forms of the
      nonperson treatment. The research is based on a street ethnography of homeless
      panhandlers living in Washington, DC.

PMID- 17541453
TI  - STRONGER THAN DIRT: Public Humiliation and Status Enhancement among Panhandlers.
AB  - Panhandlers or street beggars are a highly stigmatized collection of individuals.
      In addition to publicly displaying their homeless status, panhandlers suffer
      numerous other indignities while begging passersby for spare change. Despite
      these humiliations, many panhandlers enhance their self-regard and status by
      developing relationships with givers who become regular sources of support. These
      ongoing relationships are advanced by panhandlers who learn to present themselves
      favorably by managing emotions and stigmatized identities. This study is based on
      a street ethnography of homeless panhandlers living in Washington, D.C.

PMID- 17541454
TI  - Birth, simply.
AB  - In this column, a mother describes the home birth of her fourth child, which
      included the supportive presence of her husband, young children, and other family
      members, along with the help of a midwife. The mother's experience demonstrates
      the advantages of normal birth and its benefits to the entire family.

PMID- 17541455
TI  - Creating a global initiative.
AB  - In this guest editorial, the author describes the burgeoning efforts of an
      international collaboration to create the MotherBaby-Friendly Initiative. The
      initiative will work to improve maternity care for the women, babies, and
      families of the world.

PMID- 17541456
TI  - The lived experience of knowing in childbirth.
AB  - Research on knowing in childbirth has largely been a quantitative process. The
      purpose of this study was to understand the ways first-time mothers learn about
      birth. A phenomenological approach, using a feminist view, was used to analyze
      two in-depth interviews and journals to understand nine first-time expectant
      mothers' experiences of knowing in childbirth. The findings demonstrated a range
      of knowledge that contributed to issues of control and conflict. The participants
      also described an increased dependency on their mothers and a lack of their own
      intuition contiguous to the birth process. These findings contribute
      understanding to how expectant mothers know birth, suggesting that their knowing
      does not diminish conflict surrounding the event and may even exacerbate it when
      not combined with learning skills to manage conflict. Childbirth educators may
      want to include instruction on negotiating power differential in relationships
      encountered during childbirth in order to strengthen a first-time mother's
      ability to receive the care she wants. Educators may also want to assess the
      expectant mother's view of birth and her expectations for birth. Schools of
      nursing should consider the inclusion of women-centered care curricula at both
      the undergraduate and graduate levels. The mothers' responses in this study
      clearly reveal that the politics surrounding birthing remain in place and must be
      removed in order to provide a supportive environment for normal birth.

PMID- 17541457
TI  - Doulas as community health workers: lessons learned from a volunteer program.
AB  - Doulas, women who primarily provide social support during childbirth, have been
      associated with a number of positive health outcomes. Because the primary model
      of practice for doulas is a fee-for-service model in which families privately
      hire a doula, many expectant women who could benefit from doula support are
      unable to access the service. The Doulas Care program, located in Ann Arbor,
      Michigan, represents one model in which doulas provide services without charge.
      As a result of their extended role in the community, doulas who work with the
      Doulas Care program have unique educational needs. Through the use of focus
      groups with the program's volunteer doulas, educational needs related to
      overcoming barriers to being a doula working in the community were identified.
      Recommendations for education and training are made to improve the support doulas
      offer as community health outreach workers.

PMID- 17541458
TI  - Continuing education module: postpartum maternal health care in the United
      States: a critical review.
AB  - Postpartum maternal health care is a neglected aspect of women's health care.
      This neglect is evident in the limited national health objectives and data
      related to maternal health. Missed opportunities for enhancing the health care of
      postpartum women occur in the scope of routine postpartum care. Differing
      perceptions of maternal needs between nurses and new mothers also contribute to
      inadequate health care. Therefore, collecting national data on postpartum
      maternal morbidity, reforming postpartum care policies, providing holistic and
      flexible maternal health care, encouraging family support and involvement in
      support groups, and initiating educational programs are recommended. Further
      research is needed on issues related to postpartum maternal health.

PMID- 17541459
TI  - Home birth: the wave of the future?
AB  - A childbirth educator expresses frustration with a medical system that does not
      work for women or for many maternity care providers. She suggests out-of-hospital
      birth as an alternative. This column explores the safety of home birth, women's
      experiences of home birth, and the issues related to home birth once again being
      the standard. Childbirth educators are encouraged to present home birth as a
      viable choice.

PMID- 17541460
TI  - Using the official lamaze guide in childbirth education classes.
AB  - Normal birth has long been promoted by Lamaze International in its mission and
      vision statements and by the Lamaze Institute for Normal Birth. The Official
      Lamaze Guide: Giving Birth with Confidence, a book by Judith Lothian and
      Charlotte DeVries, can be used by birth educators to alter the focus from
      learning what to expect when one fears the worst to empowering women to
      understand that birth is usually a healthy, normal process. In this column, the
      author suggests ways in which childbirth educators can use The Official Lamaze
      Guide in their classes.

PMID- 17541461
TI  - Breastfeeding problems following anesthetic administration.
AB  - Research literature supports the notion that maternal comfort should be
      considered a priority and that mothers should receive adequate information
      regarding any drug prior to receiving that drug. Some studies indicate that
      difficulties with breastfeeding may be related to the amount of the anesthetic or
      analgesic that is administered to the mother. Thus, it seems wise to administer
      the lowest possible dose to the mother in order to minimize the amount of drug
      (or metabolite) exposure to the nursing infant. Infant exposure can be further
      reduced if breastfeeding is avoided during the times when the mother receives
      high doses of anesthetics and analgesics. However, because relatively small
      amounts of the drug are excreted into the breast milk, some mothers may opt to
      continue nursing after weighing the benefits of breastfeeding against the
      potential risk to the infant. Others may choose to "pump and dump" breast milk
      while they receive anesthetic or analgesic agents. Any concerns in this regard
      should be discussed with the anesthesia provider, preferably prior to labor or to
      any surgeries while breastfeeding.

PMID- 17541462
TI  - Research summaries for normal birth.
AB  - In this column, the author presents summaries of four research studies that
      further support the benefits of normal birth. The topics of the studies address
      cord clamping of term infants, the association of multiple cesareans and
      placental abnormalities, induction of labor at 41 weeks, and the World Health
      Organization's recently released pediatric growth charts.

PMID- 17541463
TI  - Goals.
AB  - In this column, a childbirth educator takes a humorous look at teaching methods
      and goal setting.

PMID- 17541464
TI  - High titers of Chlamydia trachomatis antibodies in Brazilian women with tubal
      occlusion or previous ectopic pregnancy.
AB  - OBJECTIVE: To evaluate serum chlamydia antibody titers (CATs) in tubal occlusion
      or previous ectopic pregnancy and the associated risk factors. METHODS: The study
      population consisted of 55 women wih tubal damage and 55 parous women. CAT was
      measured using the whole-cell inclusion immunofluorescence test and cervical
      chlamydial DNA detected by PCR. Odds ratios were calculated to assess variables
      associated with C. trachomatis infection. RESULTS: The prevalence of chlamydial
      antibodies and antibody titers in women with tubal occlusion or previous ectopic
      pregnancy was significantly higher (P < .01) than in parous women. Stepwise
      logistic regression analysis showed that chlamydia IgG antibodies were associated
      with tubal damage and with a larger number of lifetime sexual partners.
      CONCLUSIONS: Chlamydia antibody titers were associated with tubal occlusion,
      prior ectopic pregnancy, and with sexual behavior, suggesting that a chlamydia
      infection was the major contributor to the tubal damage in these women.

PMID- 17541465
TI  - Postmenopausal tuberculosis endometritis.
AB  - Tuberculosis remains a global health problem, primarily in developing countries
      with inadequate health services. A significant portion of tuberculosis in these
      settings is extrapulmonary, including tuberculosis of the genitourinary tract.
      Patients with genital tuberculosis are usually young women detected during work
      up for infertility. After menopause, tuberculosis of the endometrium is a rare
      possibility probably because of the decreased vascularity of the tissues. We
      present a case of endometrial tuberculosis with postmenopausal vaginal bleeding.

PMID- 17541467
TI  - Role of p53 and CDKN2A inactivation in human squamous cell carcinomas.
AB  - p53 tumor suppressor gene is the most commonly mutated gene in human and mouse
      cancers. Disruption of the p53 and Rb pathways is a fundamental trend of most
      human cancer cells. Inactivation of CDKN2A can lead to deregulation of these two
      pathways. Genetic abnormalities in CDKN2A gene have been well documented in human
      melanoma but their involvement in human nonmelanoma skin cancer (NMSC) and in
      particular in squamous cell carcinoma (SCC) is less clear. Several studies have
      shown that human SCCs harbour unique mutations in the p53 gene as well as
      inactivation of the CDKN2A gene. While mutations in the p53 gene are induced by
      UV radiation and represent tumor initiating events, the majority of alterations
      detected in the CDKN2A gene do not appear to be UV-dependent. In conclusion, in
      addition to p53 mutations, silencing of the CDKN2A gene might play a significant
      role in SCC development.

PMID- 17541466
TI  - The many facets of SDF-1alpha, CXCR4 agonists and antagonists on hematopoietic
      progenitor cells.
AB  - Stromal cell-derived factor-1alpha (SDF-1alpha) has pleiotropic effects on
      hematopoietic progenitor cells (HPCs). We have monitored podia formation,
      migration, proliferation, and cell-cell adhesion of human HPC under the influence
      of SDF-1alpha, a peptide agonist of CXCR4 (CTCE-0214), a peptide antagonist (CTCE
      9908), and a nonpeptide antagonist (AMD3100). Whereas SDF-1alpha induced
      migration of CD34(+) cells in a dose-dependent manner, CTCE-0214, CTCE-9908, and
      AMD3100 did not induce chemotaxis in this concentration range albeit the peptides
      CTCE-0214 and CTCE-9908 increased podia formation. Cell-cell adhesion of HPC to
      human mesenchymal stromal cells was impaired by the addition of SDF-1alpha, CTCE
      0214, and AMD3100. Proliferation was not affected by SDF-1alpha or its analogs.
      Surface antigen detection of CXCR4 was reduced upon treatment with SDF-1alpha or
      AMD3100 and it was enhanced by CTCE-9908. Despite the fact that all these
      molecules target the same CXCR4 receptor, CXCR4 agonists and antagonists have
      selective effects on different functions of the natural molecule.

PMID- 17541468
TI  - CD40-CD40L interaction in immunity against protozoan infections.
AB  - Activation of the immune system against protozoan infections relies particularly
      on two specific signals provided by cognate interaction of T cells with antigen
      presenting cells (APCs). The first signal is attributed to binding of the T-cell
      receptor (TCR) to peptide/MHC complexes on the surface of APCs, whereas the
      second signal is triggered through binding of several costimulatory molecules on
      the surface of APCs with their corresponding receptors on T cells. Among these
      costimulatory signallings, CD40/CD40L interactions have been particularly
      investigated in protozoan infection models with regard to their potential to
      amplify cell-mediated immunity against intracellular parasites. This article
      reviews current studies of the potential role of CD40/CD40L interaction in the
      modulation of immune responses against some protozoan parasites and highlights
      recent developments regarding manipulation of this interaction for promoting
      control of parasite infections.

PMID- 17541469
TI  - Tetrasomy 15q11-q13 diagnosed by FISH in a patient with autistic disorder.
AB  - We report the case of a Moroccan boy with mental retardation, hyperactivity,
      epilepsy, developmental problems and behavioural disorders. Cytogenetic analysis
      showed the presence of a supernumerary marker chromosome. Molecular cytogenetics
      allowed us to determine the marker as an inverted duplication of chromosome 15.
      It is the first case of a Moroccan patient with tetrasomy 15q in which
      fluorescence in situ hybridization (FISH) enabled us to specify the diagnosis.
      Interestingly, this patient has an infantile autism with cytogenetic
      abnormalities on chromosomal region 15q11-q13 as reported in patients with
      Autistic Disorder.

PMID- 17541470
TI  - Regulation of defense responses against protozoan infection by interleukin-27 and
      related cytokines.
AB  - Cytokine-mediated immunity is crucial in the defense against pathogens. Recently,
      IL-23 and IL-27 were identified, which along with IL-12 belong to the IL-12
      cytokine family. IL-27 is pivotal for the induction of helper T cell (Th) 1
      responses while IL-23 is important for the proliferation of memory type Th1
      cells. Recent studies revealed that IL-27 also has an anti-inflammatory property.
      In some protozoan infection, various proinflammatory cytokines were over produced
      causing lethal inflammatory responses in IL-27 receptor-deficient mice. The anti
      inflammatory effect of IL-27 depends, at least partly, on inhibition of the
      development of Th17 cells, a newly identified Th population that is induced by IL
      23 and is characterized by the production of the inflammatogenic cytokine, IL-17.
      IL-27 thus has a double identity as an initiator and as an attenuator of immune
      responses and inflammation. With the discoveries of the new IL-12-related
      cytokines and Th17 cells, Th development is facing a new paradigm.

PMID- 17541471
TI  - High-risk cutaneous squamous cell carcinoma of the head and neck.
AB  - Nonmelanoma skin cancers (squamous cell and basal cell carcinomas) occur at an
      epidemic rate in many countries with the worldwide incidence increasing. The sun
      exposed head and neck are the most frequent sites for these cancers to arise and
      in most patients diagnosed with a cutaneous squamous cell carcinoma, local
      treatment is usually curative. However, a subset is diagnosed with a high-risk
      cutaneous squamous cell carcinoma. High-risk factors include size (>2 cm),
      thickness/depth of invasion (>4 mm), recurrent lesions, the presence of
      perineural invasion, location near the parotid gland, and immunosuppression.
      These patients have a higher risk (>10-20%) of developing metastases to regional
      lymph nodes (often parotid nodes), and in some cases also of experiencing local
      morbidity (perineural invasion), based on unfavourable primary lesion and patient
      factors. Despite treatment, many patients developing metastatic cutaneous
      squamous cell carcinoma experience mortality and morbidity usually as a
      consequence of uncontrolled metastatic nodal disease. It is therefore important
      that clinicians treating nonmelanoma skin cancers have an understanding and
      awareness of these high-risk patients. The aim of this article is to discuss the
      factors that define a high-risk patient and to present some of the issues
      pertinent to their management.

PMID- 17541472
TI  - Stem cell fate analysis revisited: interpretation of individual clone dynamics in
      the light of a new paradigm of stem cell organization.
AB  - Many experimental findings on heterogeneity, flexibility, and plasticity of
      tissue stem cells are currently challenging stem cell concepts that assume a cell
      intrinsically predefined, unidirectional differentiation program. In contrast to
      these classical concepts, nonhierarchical self-organizing systems provide an
      elegant and comprehensive alternative to explain the experimental data. Here we
      present the application of such a self-organizing concept to quantitatively
      describe the hematopoietic stem cell system. Focusing on the analysis of
      individual-stem-cell fates and clonal dynamics, we particularly discuss
      implications of the theoretical results on the interpretation of experimental
      findings. We demonstrate that it is possible to understand hematopoietic stem
      cell organization without assumptions on unidirectional developmental
      hierarchies, preprogrammed asymmetric division events or other assumptions
      implying the existence of a predetermined stem cell entity. The proposed
      perspective, therefore, changes the general paradigm of thinking about stem
      cells.

PMID- 17541473
TI  - EGFR activation and ultraviolet light-induced skin carcinogenesis.
AB  - The epidermal growth factor receptor (EGFR) regulates the proliferation of
      keratinocytes through multiple mechanisms that differ depending on the
      localization of the cell within the skin. Ultraviolet (UV) irradiation, the main
      etiologic factor in the development of skin cancer, also activates the receptor.
      In this review, we discuss how the UV-induced activation of EGFR regulates the
      response of the skin to UV. UV-induced EGFR activation increases keratinocyte
      proliferation, suppresses apoptosis, and augments and accelerates epidermal
      hyperplasia in response to UV. Pharmacological inhibition of the UV-induced
      activation of EGFR in a genetically initiated mouse skin tumorigenesis model
      suppresses tumorigenesis and the activation of mitogen-activated protein (MAP)
      kinases and phosphatidyl inositol-3-kinase (PI3K)/AKT signaling pathways. EGFR
      has pleiotropic, complex, and cell-type-specific functions in cutaneous
      keratinocytes; suggesting that the receptor is an appropriate target for the
      development of molecularly targeted therapies for skin cancer and other
      pathologies.

PMID- 17541474
TI  - Inhibitory effect of inflexinol on nitric oxide generation and iNOS expression
      via inhibition of NF-kappaB activation.
AB  - Inflexinol, an ent-kaurane diterpenoid, was isolated from the leaves of Isodon
      excisus. Many diterpenoids isolated from the genus Isodon (Labiatae) have
      antitumor and antiinflammatory activities. We investigated the antiinflammatory
      effect of inflexinol in RAW 264.7 cells and astrocytes. As a result, we found
      that inflexinol (1, 5, 10 microM) suppressed the expression of inducible nitric
      oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) as well as the production of
      nitric oxide (NO) in LPS-stimulated RAW 264.7 cells and astrocytes. Consistent
      with the inhibitory effect on iNOS and COX-2 expression, inflexinol also
      inhibited transcriptional and DNA binding activity of NF-kappaB via inhibition of
      IkappaB degradation as well as p50 and p65 translocation into nucleus. These
      results suggest that inflexinol inhibits iNOS and COX-2 expression through
      inhibition of NF-kappaB activation, thereby inhibits generation of inflammatory
      mediators in RAW 264.7 cells and astrocytes, and may be useful for treatment of
      inflammatory diseases.

PMID- 17541480
TI  - Co(III) and Ni(II) complexes containing bioactive ligands: synthesis, DNA
      binding, and photocleavage studies.
AB  - DNA binding and photocleavage characteristics of a series of mixed ligand
      complexes of the type [M(bpy)(2)qbdp](PF(6))(n).xH(2)O (where M = Co(III) or
      Ni(II), bpy = 2.2'-bipryidine, qbdp = Quinolino[3,2-b]benzodiazepine, n = 3 or 2
      and x = 5 or 2) have been investigated. The DNA binding property of the complexes
      with calf thymus DNA has been investigated by using absorption spectra, viscosity
      measurements, as well as thermal denaturation studies. Intrinsic binding constant
      (K(b)) has been estimated under similar set of experimental conditions.
      Absorption spectral studies indicate that the Co(III) and Ni(II) complexes
      intercalate between the base pairs of the CT-DNA tightly with intrinsic DNA
      binding constant of 1.3 x 10(6) and 3.1 x 10(5) M(-1) in Tris-HCl buffer
      containing 50 mM NaCl, respectively. The proposed DNA binding mode supports the
      large enhancement in the relative viscosity of DNA on binding to quinolo[3,2
      b]benzodiazepine. The oxidative as well as photo-induced cleavage reactions were
      monitered by gel electrophoresis for both complexes. The photocleavage
      experiments showed that the cobalt(III) complex can cleave pUC19 DNA effectively
      in the absence of external additives as an effective inorganic nuclease.

PMID- 17541481
TI  - Platinum(II) and palladium(II) complexes of pyridine-2-carbaldehyde
      thiosemicarbazone as alternative antiherpes simplex virus agents.
AB  - The cytotoxicity and the antivirus activity of Pd(II) and Pt(II) complexes with
      pyridine-2-carbaldehyde thiosemicarbazone (HFoTsc) against HSV replication were
      evaluated on four HSV strains-two wt strains Victoria (HSV-1) and BJA (HSV-2) and
      two ACV(R) mutants with different tk gene mutations R-100 (TK(A), HSV-1) and PU
      (TK(N), HSV-2). The experiments were performed on continuous MDBK cells and four
      HSV 1 and HSV 2 strains were used, two sensitive to acyclovir and two resistant
      mutants. The five complexes of HFoTsc, [Pt(FoTsc)Cl],
      [Pt(FoTsc)(H(2)FoTsc)]Cl(2), [Pt(FoTsc)(2)], [Pd(FoTsc)(H(2)FoTsc)]Cl(2), and
      [Pd(FoTsc)(2)], were found to be effective inhibitors of HSV replication. The
      most promising, active, and selective anti-HSV agent was found to be complex
      [Pt(FoTsc)(H(2)FoTsc)]Cl(2). This complex could be useful in the treatment of HSV
      infections, since it is resistant to ACV mutants. PCR study of immediate early
      300 bp ReIV Us1 region reveals that the complex [Pt(FoTsc)(H(2)FoTsc)]Cl(2)
      specifically suppressed wt HSV-1 genome 2 hours after the infection, not inducing
      apoptosis/necrosis on the 8 hours after virus infection. The target was found to
      be most probably the viral, instead of the host cell DNA.

PMID- 17541483
TI  - Quantitative structure-activity relationships and mixture toxicity of substituted
      benzaldehydes to Photobacterium phosphoreum.

PMID- 17541484
TI  - Alkali and transition metals in macrophytes of a wetland system.

PMID- 17541485
TI  - Effect of daidzein in rats on cadmium excretion.

PMID- 17541486
TI  - Persistence of acetamiprid in soil.

PMID- 17541487
TI  - Dissolved organochlorine and PAH pollution profiles in Lithuanian and Swedish
      surface waters.
AB  - In recent decades, knowledge and concern regarding persistent organic pollutants
      and the environmental hazards they may pose have increased considerably, leading
      to international agreements such as the United Nations environment program
      Stockholm convention on persistent organic pollutants (POPs), to minimize further
      release of POPs into the environment (UNECE Protocol, 1979; UNEP Stockholm
      convention, 2001; UNECE Convention, 1998). National POP monitoring programs
      should be designed to identify, characterize and address the release of the POPs
      listed in the Stockholm convention. However, analyses of grab samples only
      provide crude snapshots of total concentrations at single points in space and
      time, which may be highly unrepresentative of average concentrations, and fail to
      account for differences in the POPs' bioavailability and various other relevant
      factors. To obtain a better understanding of the fate and availability of
      pollutants in the environment it is necessary to obtain data regarding their site
      specific and regional exposure levels. Exposure levels expressed in terms of
      total chemical concentrations do not reflect the actual exposure of organisms,
      and thus may not accurately reflect the true risks posed. Therefore,
      environmental monitoring programs would be improved by using reliable,
      integrative sampling methods that would not only allow time-weighted average
      concentrations of pollutants in the environment to be determined, but also
      facilitate assessments of the risks these chemicals pose to the environment.

PMID- 17541488
TI  - Influence of wheat ash on the MCPA immobilization in agricultural soils.

PMID- 17541489
TI  - Hotline update of clinical trials and registries presented at the German Cardiac
      Society Meeting 2007: 2L-Registry, Kardio-Pro, EVER, AFFECT, VTACH, ARTS II,
      OPTAMI, PEPCAD I, PEPCAD II, GERSHWIN, SPICE, FIX-CHF and CREDIT.
AB  - This article summarizes the results of a number of new clinical trials,
      registries and metaanalyses in the field of cardiovascular medicine. Key
      presentations made at the 73(rd) annual meeting of the German Cardiac Society,
      held in Mannheim, Germany, in April 2007 are reported. The data were presented by
      leading experts in the field with relevant positions in the trials, registries or
      metaanalyses. These comprehensive summaries should provide the readers with the
      most recent data on diagnostic and therapeutic developments in cardiovascular
      medicine.

PMID- 17541490
TI  - Characteristics and management of ruptured distal middle cerebral artery
      aneurysms.
AB  - OBJECTIVE: Distal middle cerebral artery (dMCA) aneurysms are very rare with a
      reported frequency of 2-6%. Typically, patients with ruptured distal MCA
      aneurysms have poor clinical outcomes because often there is both a subarachnoid
      haemorrhage (SAH) and an intracerebral haematoma (ICH). The goals of this study
      were to identify the characteristics of the distal MCA aneurysms and evaluate the
      optimal treatment for a good outcome. METHODS: The clinical, neuroradiological
      and operative records of 8 patients with a ruptured distal MCA aneurysm who
      underwent surgical management were reviewed retrospectively. The outcomes were
      presented according to the Glasgow Outcome Scale (GOS). RESULTS: The clinical
      characteristics of the patients with ruptured dMCA aneurysms included the
      following: (1) a fusiform appearance in five out of eight (63%) patients. (2)
      Mean aneurysm size of 9.4 mm (range 2-35 mm). (3) The location being M2 (insular
      segment) in three, M2-3 junction in three, and M3 (opercular segment) in two
      patients. (4) Brain CT images revealed both SAH and an ICH in six of eight (75%)
      patients with the mean size of the ICH being 10 cc (range 5-25 cc). (5) Re
      bleeding occurred in four out of eight (50%) of patients. All patients underwent
      early surgical treatment and the procedures used for surgical repair were,
      clipping in five patients, trapping in two, and trapping with end-to-end bypass
      surgery in one patient. Clinical outcomes were poor in two patients (death) due
      to severe brain swelling. CONCLUSIONS: In this study, dMCA aneurysms had a
      fusiform shape and a high re-bleeding rate; if ruptured, there was generally ICH
      and SAH. A good clinical outcome was associated with adequate control of brain
      swelling and early surgery to prevent re-bleeding.

PMID- 17541491
TI  - A calcified foreign body in the bladder after laparoscopic inguinal hernia
      repair.
AB  - In this paper, we report an exceedingly rare complication after laparoscopic
      inguinal hernioplasty. A 57-year-old man was submitted to transurethral resection
      of the prostate followed by laparoscopic "bikini mesh" hernia repair. One year
      later, he presented with miccional irritative symptoms. Ultrasonography showed a
      vesical intraluminal foreign body and computerized tomography revealed a
      calcified foreign body on the anterior bladder wall. On reoperation, it was noted
      that there occurred mesh transfixation of the bladder. The lateral segments were
      removed and the patient recovered uneventfully. This is a, thus far, unpublished
      complication of this technique.

PMID- 17541492
TI  - Amyand's hernia in premature neonates: report of two cases.
AB  - The finding of a normal or inflamed vermiform appendix within an inguinal hernia
      is termed Amyand's hernia. It is extremely rare in children, especially in
      infants and neonates. When it occurs, it is usually misdiagnosed as an
      irreducible or strangulated inguinal hernia, and the accurate diagnosis is made
      intraoperatively. We report two cases of Amyand's hernia in premature neonates.
      Both patients presented on admission with signs and symptoms indicating a
      strangulated right inguinal hernia, and the accurate diagnosis was made
      intraoperatively. One of them had progressed to local peritonitis. Appendicectomy
      and hernia repair were made at the same time through an inguinal transverse
      incision, and the postoperative course was uneventful in both. We point out the
      need to consider acute appendicitis in the differential diagnosis of strangulated
      right inguinal hernia.

PMID- 17541493
TI  - A survey of inguinal hernia repair in Wales with special emphasis on laparoscopic
      repair.
AB  - BACKGROUND: The National Institute of Clinical Excellence (NICE) recently
      published its guidance on the use of laparoscopic repair for inguinal hernias.
      This study aimed to assess the likely uptake of laparoscopic surgery for inguinal
      hernias in Wales. In addition the current practice with regards to day case
      surgery, use of local anaesthesia, antibiotic prophylaxis, thromboembolic
      prophylaxis and advice regarding convalescence was assessed. METHODS: A postal
      questionnaire survey of all consultant surgeons (n = 91) in Wales was performed.
      RESULTS: There was a 70% (n = 67) response to the questionnaire. Fifteen percent
      of surgeons (n = 9) perform laparoscopic inguinal hernia repair in Wales; 10% of
      surgeons in Wales agreed with the NICE guidance. Lichtenstein hernia repair was
      the most commonly used the technique to repair primary inguinal hernias in Wales
      (82%). No surgeon currently is using a laparoscopic repair as the technique of
      choice for repair of primary inguinal hernias. Eighteen percent of surgeons
      perform all the procedures as day cases; 15% of surgeons perform more than 90% of
      the procedures under local anaesthesia; 44% of surgeons do not use any form of
      thromboprophylaxis for elective inguinal hernia repair, while 78% of the surgeons
      used routine antibiotic prophylaxis. Post-operative advice regarding return to
      sedentary work and driving was highly variable (1-4 weeks), as was advice
      regarding heavy work and sport (2-12 weeks). CONCLUSIONS: The uptake of
      laparoscopic surgery for inguinal hernia repair in Wales is low. Only a minority
      of surgeons agree with the NICE guidance. Similarly the uptake of day case repair
      and the use of local anaesthesia are minimal. The use of antibiotic and
      thromboembolic prophylaxis is empirical and inconsistent. There is a need for
      evidence-based guidelines to standardise the antibiotic prophylaxis, TE
      prophylaxis and advice regarding post-operative advice.

PMID- 17541494
TI  - "Fatto il polipropilene": a tribute to Giulio Natta.

PMID- 17541495
TI  - Laparoscopic repair of direct inguinal hernia: a new technique that reduces the
      development of postoperative seroma.
AB  - BACKGROUND: Seroma are common early postoperative complications encountered in
      laparoscopic inguinal hernia repair. Previous anecdotal evidence from our
      surgical practice suggested a lower incidence of postoperative seroma formation
      with direct hernia repairs when the lax transversalis fascia (TF) is inverted by
      tacking to the pubic ramus. We undertook a study to investigate whether TF
      inversion in this way reduces the incidence of postoperative seroma. METHOD: A
      total of 216 patients undergoing transabdominal preperitoneal (TAPP) laparoscopic
      inguinal hernia repairs from August 2003 to December 2005 were included in this
      prospective non-randomised controlled study. Surgeon 1 would routinely invert the
      TF whereas surgeon 2 would not. At follow-up the presence of postoperative seroma
      and pain was recorded. RESULTS: Mann-Whitney U test demonstrated no significant
      difference in terms of age, sex and time to follow-up between the surgeons'
      patient groups (P > 0.05), and Chi-square test demonstrated significantly that
      inversion of the TF is associated with a lower incidence of postoperative seroma
      (P < 0.05). There was no significant difference in terms of postoperative pain at
      follow-up. CONCLUSION: Inversion of the TF is associated with a statistically
      lower incidence of postoperative seroma, without increasing postoperative pain
      despite the use of one or two additional tacks.

PMID- 17541496
TI  - Unusual manifestation of histoplasmosis in connective tissue diseases.
AB  - This report describes the coexistence of three patients with rheumatic diseases
      (systemic lupus erythematosus, rheumatoid arthritis, and dermatomyositis) and
      infections because of Histoplasma capsulatum. Connective tissue diseases and
      histoplasmosis share several clinical findings. Therefore, histoplasmosis could
      be misdiagnosed as connective tissue disease or a flare of these diseases. Such
      cases highlight the importance of awareness of histoplasmosis in
      immunocompromised patients, particularly in those originating from endemic areas.

PMID- 17541497
TI  - Use of complementary and alternative medicine by rheumatoid arthritis patients in
      Korea.
AB  - This study measured the prevalence of use of complementary and alternative
      medicine (CAM) in Korean patients with rheumatoid arthritis (RA). A trained nurse
      conducted 20-min questionnaire-based interviews at the hospitals when each
      patient visited as an outpatient. The questionnaire included questions on
      demographic information, clinical information, and the use of CAM. Of the 153
      respondents, 125 (82%) had used CAM; 37% of those who used CAM had started taking
      CAM products following suggestions from family members and other relatives. In
      users of CAM, 35% considered that it improved the symptoms of RA, and 14% felt it
      was effective in achieving psychological relaxation. We categorized treatment
      into six CAM categories used by the respondents: 84.0% of patients used
      traditional Oriental medical treatments, 70.4% used plant- and animal-derived
      over-the-counter health care products, and 13.6% used manual therapies. Most RA
      patients (64%) would like to try a new type of CAM. About half of the respondents
      (48%) expected to receive information about CAM from their general practitioner
      even if most (72%) did not discuss their use of CAM with their doctor. Most of
      the RA patients in this study used CAM, and half reported beneficial effects.
      Despite the presence of adverse side effects, patients tended to use CAM without
      discussing it with their main physicians, suggesting that physicians should be
      actively involved in the prescription and use of CAM.

PMID- 17541498
TI  - Soluble receptor activator of NFkappa B-ligand and osteoprotegerin in rheumatoid
      arthritis - relationship with bone mineral density, disease activity and bone
      turnover.
AB  - The aim of our study was to investigate determinants of bone mineral density
      (BMD) measured by dual X-ray absorptiometry at the lumbar spine (BMD-LS) and at
      the femoral neck (BMD-FN) in patients with rheumatoid arthritis (RA) with special
      respect to bone resorbing proinflammatory cytokines and their physiological
      antagonists. In 142 RA patients the following parameters were measured in
      parallel with BMD: serum levels of soluble receptor activator of nuclear factor
      kappa-B-ligand (sRANKL), osteoprotegerin (OPG), interleukin (IL)-6, soluble
      glycoprotein 130 (sgp130), 25-hydroxyvitamin D3 (25OHD(3)), 1,25-dihydroxyvitamin
      D3 (1,25[OH](2)D(3)), intact parathyroid hormone, osteocalcin, ionized calcium,
      renal excretion of pyridinolin and deoxypyridinolin, C-reactive protein, and
      erythrocyte sedimentation rate (ESR). No significant differences of sRANKL, OPG,
      IL-6, and spg130 were found between patients with osteoporosis (47.9% of
      patients), osteopenia (36.6%), and normal BMD (15.5%). However, total sRANKL was
      significantly higher in postmenopausal women with osteoporosis at FN than in
      those without (p < 0.05) and showed a negative correlation with BMD-LS in
      patients older than 60 years (p = 0.01). BMD-LS and BMD-FN (p < 0.001) and total
      sRANKL (p < 0.01) were negatively related with the age of the patients. Only IL-6
      (positive correlation, p < 0.001) and 1,25(OH)(2)D(3) (negative correlation, p <
      0.001) but not sRANKL, OPG, and sgp130 were related to disease activity. Using
      multiple linear regression analysis, menopause was identified as the crucial
      negative determinant of BMD-LS (R (2) = 0.94, p = 0.001), whereas cumulative
      glucocorticoid dose (beta = -0.80, p = 0.001) and ESR (beta = -0.44, p = 0.016)
      were the negative determinants of BMD-FN (R (2) = 0.86, p = 0.001). The results
      indicate that influences of age and gender must be considered in investigations
      on the relationship between BMD and sRANKL in RA and that high serum levels of
      sRANKL seems to be associated with osteoporosis only in subgroups of RA patients.

PMID- 17541499
TI  - Neurogenic osteoarthropathy in leprosy.
AB  - According to World Health Organization (WHO), the global registered prevalence of
      leprosy at the beginning of 2006 stood at 219,826 cases. Pockets of high
      endemicity still remain in some areas of Africa, India, and Brazil. One of the
      joint manifestations of leprosy are the signs of Charcot's disease. Charcot's
      disease of leprosy advanced in spite of the treatment. The different clinical
      types are sometimes a problem in diagnosis. We report herein two cases.

PMID- 17541500
TI  - Characterization of magnetic colloids by means of magnetooptics.
AB  - A new, efficient method for the characterization of magnetic colloids based on
      the Faraday effect is proposed. According to the main principles of this
      technique, it is possible to detect the stray magnetic field of the colloidal
      particles induced inside the magnetooptical layer. The magnetic properties of
      individual particles can be determined providing measurements in a wide range of
      magnetic fields. The magnetization curves of capped colloids and paramagnetic
      colloids were measured by means of the proposed approach. The registration of the
      magnetooptical signals from each colloidal particle in an ensemble permits the
      use of this technique for testing the magnetic monodispersity of colloidal
      suspensions.

PMID- 17541501
TI  - Theory of microphase separation on side-chain liquid-crystalline polymers with
      flexible spacers.
AB  - We model a melt of monodisperse side-chain liquid-crystalline polymers as a melt
      of comb copolymers in which the side groups are rod-coil diblock copolymers. We
      consider both excluded-volume and Maier-Saupe interactions. The first acts among
      any pair of segments while the latter acts only between rods. Using a free-energy
      functional calculated from this microscopic model, we study the spinodal
      stability of the isotropic phase against density and orientational fluctuations.
      The phase diagram obtained in this way predicts nematic and smectic instabilities
      as well as the existence of microphases or phases with modulated wave vector but
      without nematic ordering. Such microphases are the result of the competition
      between the incompatibility among the blocks and the connectivity constraints
      imposed by the spacer and the backbone. Also the effects of the polymerization
      degree and structural conformation of the monomeric units on the phase behavior
      of the side-chain liquid-crystalline polymers are studied.

PMID- 17541502
TI  - Effect of interfacial slippage in peel test: theoretical model.
AB  - Peel test is an efficient method to assess the performance and characteristics of
      materials such as adhesives and adhesive tapes. Recent experiments evidenced that
      the measured adhesive strength is closely related to the shear-induced
      interfacial slippage near the delamination front due to the concomitant Poisson
      contraction effect of the adhesive. Based on the experimental observations, a
      theoretical model is presented in this paper to examine the effect of the shear
      induced interfacial slippage in the peel test. The influence of the interfacial
      slippage, represented by the shear displacement in the cohesive zone, on the
      fracture energy of decohesive zone is analyzed. An implicit expansion method with
      a Gauss-Chebyshev quadrature scheme is used to derive the solution. It is found
      that the length of the slippage zone and the receding contact angle of adhesives
      are the two most significant contributors to the total fracture energy of the
      decohesive zone. These results demonstrate that the mechanism of interfacial
      slippage plays a significant role in the adhesion and peeling behaviors of
      adhesives.

PMID- 17541503
TI  - Improvement of the multiple-stress tolerance of an ethanologenic Saccharomyces
      cerevisiae strain by freeze-thaw treatment.
AB  - An effective, simple, and convenient method to improve yeast's multiple-stress
      tolerance, and ethanol production was developed. After an ethanologenic
      Saccharomyces cerevisiae strain SC521 was treated by nine cycles of freeze-thaw,
      a mutant FT9-11 strain with higher multiple-stress tolerance was isolated, whose
      viabilities under acetic acid, ethanol, freeze-thaw, H(2)O(2), and heat-shock
      stresses were, respectively, 23-, 26-, 10- and 7-fold more than the parent strain
      at an initial value 2 x 10(7) c.f.u. per ml. Ethanol production of FT9-11 was
      similar (91.5 g ethanol l(-1)) to SC521 at 30 degrees C with 200 g glucose l(-1),
      and was better than the parent strain at 37 degrees C (72.5 g ethanol l(-1)),
      with 300 (111 g ethanol l(-1)) or with 400 (85 g ethanol l(-1)) g glucose l(-1).

PMID- 17541504
TI  - Transport of heterologous proteins to the periplasmic space of Pseudomonas
      fluorescens using a variety of native signal sequences.
AB  - Bacterial expression of recombinant proteins containing disulfide bonds is
      facilitated by transport of the proteins to the periplasmic space. Several
      Pseudomonas fluorescens signal sequences have been identified that efficiently
      direct proteins to the periplasm and provide solubility and yield advantages over
      the production of proteins fused to the PelB signal sequence in E. coli. For a
      single chain antibody fragment, the final yield varied from about 1 g/l to 10 g/l
      when expression in P. fluorescens involved fusion to various P. fluorescens
      signal sequences.

PMID- 17541505
TI  - Production of D-lactic acid from sugarcane molasses, sugarcane juice and sugar
      beet juice by Lactobacillus delbrueckii.
AB  - Lactobacillus delbrueckii was grown on sugarcane molasses, sugarcane juice and
      sugar beet juice in batch fermentation at pH 6 and at 40 degrees C. After 72 h,
      the lactic acid from 13% (w/v) sugarcane molasses (119 g total sugar l(-1)) and
      sugarcane juice (133 g total sugar l(-1)) was 107 g l(-1) and 120 g l(-1),
      respectively. With 10% (w/v) sugar beet juice (105 g total sugar l(-1)), 84 g
      lactic acid l(-1) was produced. The optical purities of D: -lactic acid from the
      feedstocks ranged from 97.2 to 98.3%.

PMID- 17541506
TI  - Simplified soy molasses-based medium for reduced-cost production of sophorolipids
      by Candida bombicola.
AB  - A simplified medium containing only soy molasses and oleic acid as ingredients
      was developed for the production of sophorolipids (SLs) from Candida bombicola.
      We achieved a product yield of 53 +/- 3 g of purified sophorolipids per liter of
      starting culture volume, which is 71 +/- 4% of the yield obtained with growth
      medium that also additionally contains the costly yeast extract and urea as
      nitrogen source. The large majority of the SL components existed in the lactone
      form (87%), and the predominant component is SL containing (omega-1)-hydroxyoleic
      acid as the lipid moiety. The study demonstrated for the first time the
      usefulness of the low-value soy molasses as a combined nitrogen- and carbon
      source for SL production at a reduced cost.

PMID- 17541507
TI  - Effects of flavonoid on calcium content in femoral tissue culture and parathyroid
      hormone-stimulated osteoclastogenesis in bone marrow culture in vitro.
AB  - The effect of various flavonoids, which are present in food and plants, on bone
      calcium content and osteoclastogenesis were investigated to compare action of
      flavonoid on bone formation and bone resorption in vitro. Rat femoral-diaphyseal
      (cortical bone) and -metaphyseal (trabecular bone) tissues were cultured for 48 h
      in Dulbecco's modified Eagle's medium (high glucose) supplemented with
      antibiotics and bovine serum albumin. Amoung quercetin, myricetin, kaempferol,
      isorhamnetin, curcumin, hesperidin, or astaxanthin in the range of 10(-7)-10(
      5)M, culture with quercetin (10(-6) or 10(-5)M) caused a significant increase in
      diaphyseal calcium content. Such an effect was not seen in other compounds. Mouse
      bone marrow cells were cultured for 7 days in the presence of parathyroid hormone
      (PTH; 10(-7)M), a bone-resorbing factor, in vitro. Culture with PTH caused a
      significant increase in osteoclast-like cell formation. This increase was
      significantly inhibited in the presence of quercetin, myricetin, kaempferol,
      isorhamnetin, or curcumin in the range of 10(-8)-10(-6)M. Such an effect was not
      seen in the case of hesperidin or astaxanthin. In addition, culture with PTH (10(
      7)M) caused a significant decrease in diaphyseal calcium content. This decrease
      was completely prevented in the presence of quercetin, myricetin, kaempferal, or
      isorhamnetin of 10(-6)M. This study demonstrates that various flavonoids have a
      potent inhibitory effect on osteoclastogenesis and bone resorption rather than
      bone formation in vitro. Among various flavonoids, quercetin had a stimulatory
      effect on bone formation and an inhibitory effect on bone resorption in vitro.

PMID- 17541508
TI  - Effects of streptozotocin-induced diabetes on action potentials in the sinoatrial
      node compared with other regions of the rat heart.
AB  - In vivo biotelemetry studies have demonstrated that heart rate (HR) is
      progressively and rapidly reduced after administration of streptozotocin (STZ)
      and that the reduction in HR can be partially normalized with insulin
      replacement. Reductions in HR have also been reported in isolated perfused heart
      and superfused right atrial preparations suggesting that intrinsic defects in the
      heart are at least partly responsible for the bradycardia. The regional effects
      of STZ-induced diabetes mellitus (DM) on action potentials (APs) in the
      sinoatrial node (SAN), right and left atria and ventricles have been compared in
      the spontaneously beating Langendorff perfused rat heart 10-12 weeks after
      treatment. HR was significantly reduced in STZ-induced diabetic rat heart (174 +/
      9 BPM) compared to controls (241 +/- 12 BPM). The duration of AP repolarization
      at 50% and 70% from peak AP was significantly prolonged in SAN, right atrium and
      right ventricle from STZ-induced diabetic rat compared to age-matched controls.
      In the SAN AP duration (APD) at 50% and 70% were 51.7 +/- 2.2 and 59.5 +/- 2.3 ms
      in diabetic rat heart compared to 45.2 +/- 1.7 and 50.0 +/- 1.6 ms in controls,
      respectively. In contrast APD at 50% and 70% were not significantly altered in
      the left atrium and left ventricle. Regional defects in the expression and/or
      electrophysiology of SAN ion channels, and in particular those involved in AP
      repolarization, might underlie heart rhythm disturbances in the STZ-induced DM
      rat.

PMID- 17541509
TI  - Nitric oxide suppresses preadipocyte differentiation in 3T3-L1 culture.
AB  - Nitric oxide (NO) is an important chemical messenger controlling many
      physiological functions, involving cell proliferation, and differentiation. The
      purpose of this study was to investigate the effect of NO on adipocyte
      differentiation using a murine preadipocyte cell line, 3T3-L1. The treatment with
      a NO donor, 1-hydroxy-2-oxo-3,3-bis(2-aminoethyl)-1-triazene (NOC18), reduced
      some markers of adipocyte differentiation such as glycerol-3-phosphate
      dehydrogenase activity, and intracellular lipid accumulation. To examine whether
      these effects of NOC18 on adipocyte differentiation markers are due to its
      cytotoxity, lactate dehydrogenase (LDH) release from the cells were measured.
      NOC18 did not affect LDH release into the culture medium. Thus, the suppressive
      actions of NO donor were unlikely to result from its cytotoxicity. Peroxisome
      proliferator-activated receptor (PPAR) gamma is a critical transcription factor
      for adipocyte differentiation and adipocyte fatty acid binding protein (aP2) gene
      is one of its targets. Protein expression of PPARgamma was not diminished by
      NOC18 treatment, although mRNA expression of aP2 was reduced. Electrophoretic
      mobility shift assay showed that NOC18 interfered with the DNA binding activity
      of PPARgamma. Therefore, the present experiment suggest that NO suppresses
      adipocyte differentiation through suppressing the transcriptional activity of
      PPARgamma, without suppressing its expression level.

PMID- 17541510
TI  - [Abstracts of the 113th Congress of the German Society of Internal Medicine,
      2007].

PMID- 17541511
TI  - SVCT1 and SVCT2: key proteins for vitamin C uptake.
AB  - Vitamin C is accumulated in mammalian cells by two types of proteins: sodium
      ascorbate co-transporters (SVCTs) and hexose transporters (GLUTs); in particular,
      SVCTs actively import ascorbate, the reduced form of this vitamin. SVCTs are
      surface glycoproteins encoded by two different genes, very similar in structure.
      They show distinct tissue distribution and functional characteristics, which
      indicate different physiological roles. SVCT1 is involved in whole-body
      homeostasis of vitamin C, while SVCT2 protects metabolically active cells against
      oxidative stress. Regulation at mRNA or protein level may serve for preferential
      accumulation of ascorbic acid at sites where it is needed. This review will
      summarize the present knowledge on structure, function and regulation of the SVCT
      transporters. Understanding the physiological role of SVCT1 and SVCT2 may lead to
      develop new therapeutic strategies to control intracellular vitamin C content or
      to promote tissue-specific delivery of vitamin C-drug conjugates.

PMID- 17541512
TI  - Assessment of setup accuracy in patients receiving postmastectomy radiotherapy
      using electronic portal imaging.
AB  - PURPOSE: The aim of this study was to investigate the setup accuracy for patients
      undergoing postmastectomy radiotherapy using electronic portal imaging. MATERIALS
      AND METHODS: Ten patients undergoing radiotherapy via tangent (TG),
      supraclavicular-axillary (SA), and internal mammary (IM) fields were included. To
      explore the setup accuracy, distances between chosen landmarks were taken as
      reference parameters (RPs). The difference between measured RPs on simulation
      films and electronic portal images (EPIs) was calculated as the setup error.
      RESULTS: A total of 30 simulation films and 120 EPIs were evaluated. In the SA
      field, calculated RPs were lung length (LL), clavicle-field center perpendicular
      distance, and clavicle-field center transverse distance. The mean of the standard
      deviations (SDs) of the random errors (sigma) for these parameters were 4.7, 7.3,
      and 7.6; and the SDs of the systematic errors (Sigma) were 6.8, 4.4, and 13.5,
      respectively. In the TG fields, the calculated RPs were the central lung distance
      (CLD), maximum lung distance (MLD), and central soft-tissue distance (CSTD). In
      the medial TG field, the sigma values for these parameters were 3.4, 3.6, and
      4.1, respectively; and the sigma values were 6.6, 2.6, and 3.4, respectively. In
      the lateral TG field, Sigma values for the calculated RPs were 2.4, 3.2, and
      3.3l, respectively; and the Sigma values were 5.6, 3.6, and 4.8, respectively.
      CONCLUSION: CLD, MLD, and CSTD in TG fields and LL in SA fields are easily
      identifiable and are helpful for detecting setup errors using EPIs in patients
      undergoing postmastectomy radiotherapy.

PMID- 17541513
TI  - Explanation for the failure of neoadjuvant chemotherapy to improve outcomes after
      radiotherapy for locally advanced uterine cervical cancer from the standpoint of
      the tumor regression rate.
AB  - PURPOSE: Treatment outcomes for patients with locally advanced cervical cancer
      are no better with neoadjuvant chemotherapy (NAC) combined with radiotherapy (RT)
      than with RT alone. We investigated the reason for this failure from the
      standpoint of the tumor regression rate (RR). MATERIALS AND METHODS: A total of
      48 patients with clinical stage IIB-IVA cervical squamous cell carcinoma were
      treated clinically with cisplatin-based NAC plus RT (n = 15) or RT alone (n =
      33). The RR was defined as the slope of a tumor shrinkage curve derived with
      magnetic resonance images. The local control rate (LCR) and disease-free rate
      (DFR) were estimated by clinical stage (IIB vs. III-IVA), pretreatment volume (<
      or = median vs. > median), lymph node status (negative vs. positive), treatment
      type, overall treatment time (< or =8 weeks vs. >8 weeks), and RR (< or = median
      vs. > median) using univariate and multivariate analyses. RESULTS: RR during NAC
      or during NAC and RT (n = 15) was not significantly higher than RR by RT alone (n
      = 33). Low RR and positive nodal status were significantly powerful prognostic
      factors for both the LCR and DFR, whereas the others were not. CONCLUSION:
      Although effective in reducing tumor volume prior to RT, NAC showed no overall
      effect in increasing the RR, which was shown to be the most powerful prognostic
      factor.

PMID- 17541514
TI  - Revisit image control for pediatric chest radiography.
AB  - PURPOSE: The aim of this study was to analyze the fraction defectiveness and
      efficacy of the patient immobilization device (PID) for pediatric chest
      radiography. MATERIALS AND METHODS: We examined 840 plain chest radiographs in
      six hospitals, including four children's hospitals and two general hospitals. The
      mean age of the patients was 1.9 years (range 0-5 years). Two board-qualified
      pediatric radiologists rated (into three grades, by consensus) the degree of
      inspiration, rotation, lordosis, scoliosis, and cutoff or coning as well as the
      quality of the chest radiographs. RESULTS: The incidence of "poor" and "very
      poor" quality examinations was 2/140 and 3/140 in each of two children's
      hospitals using PID. The corresponding figures were 9/139 and 17/140 in the two
      children's hospitals that did not use PID. The general hospital using PID had
      14/140 "poor" and "very poor" examinations. The general hospital that did not use
      PID had 28/140 "poor" and "very poor" examinations. Thus, statistically better
      quality chest radiography was obtained with the use of PID (P < 0.001). Likewise,
      rotation, lordosis, and scoliosis were less frequently diagnosed as present when
      PID was used (P < 0.001, 0.001, 0.05). Cutoff or coning had no relation to the
      use of PID (P = 0.13). No significant difference was found between the degree of
      inspiration and the use of PID (P = 0.56). CONCLUSION: Fraction defectiveness in
      the general hospital that did not use PID was as much as 14 times higher than
      that of the children's hospitals that used PID. The patient immobilization device
      is recommended for hospitals with technologists not specifically trained for
      pediatric examination.

PMID- 17541515
TI  - Serial assessment of left ventricular function in various patient groups with Tl
      201 gated myocardial perfusion SPECT.
AB  - PURPOSE: The present study was performed to assess stress-related left
      ventricular (LV) function variations in various patient groups and to determine
      if they were affected by sex or the type of stress experienced. We used thallium
      (Tl)-201 gated myocardial perfusion single-photon emission computed tomography
      (SPECT) for the analysis. MATERIALS AND METHODS: A total of 270 patients were
      examined by electrocardiography-gated myocardial perfusion SPECT imaging to
      assess LV function. After injection of Tl-201 at a dose of 111 MBq at peak
      stress, SPECT scans were acquired at 10 min (after stress) and 3 h (rest) after
      injection on a three-headed camera. RESULTS: In the normal perfusion group, the
      mean LV ejection fraction (LVEF) was significantly higher, and both the end
      diastolic volume index (EDVI) and end-systolic volume index (ESVI) were
      significantly lower in women than in men (P < 0.05). Poststress stunning occurred
      in 29 of 98 patients (30.0%) in the ischemia group and in 42 of 90 patients
      (46.7%) in the fixed group. There was a significant difference in poststress
      stunning between bicycle ergometer stress and dipyridamole stress (P < 0.05).
      CONCLUSION: In patients with normal perfusion, LVEF, EDVI, and ESVI determined by
      gated Tl-201 SPECT should be corrected for sex. In addition, the influence of the
      type of stress should be considered when assessing stress-related LV function
      variations.

PMID- 17541516
TI  - Arteriovenous malformation of the gallbladder: CT and angiographic findings.
AB  - We encountered a case of arteriovenous malformation (AVM) of the gallbladder in a
      patient with hepatocellular carcinoma (HCC). Contrast-enhanced computed
      tomography (CT) showed serpentine vessels around and within the gallbladder wall.
      Angiography showed dilated and tortuous cystic arteries, a racemose vascular
      network, and early-filling cystic veins. Transcatheter arterial embolization of
      two cystic arteries feeding the AVM was performed with platinum microcoils prior
      to transcatheter arterial chemoembolization for HCC to prevent embolic particles
      from flowing into these arteries. Follow-up contrast-enhanced CT showed blood
      flow in the gallbladder AVM, which appeared to be fed by the arterial
      collaterals.

PMID- 17541517
TI  - Notes on the application of the Matsui-Kitamura stent-graft for endovascular
      repair of abdominal aortic aneurysm.
AB  - Abdominal aortic and left common iliac aneurysms in a 79-year-old man who had
      undergone Miles' operation for rectal carcinoma were treated with endovascular
      repair of an abdominal aortic aneurysm (EVAR), taking into consideration the age,
      surgical history, and wishes of the patient and his family. The Matsui-Kitamura
      stent-graft (MK-SG) was designed based on preoperative angiographic mapping. At
      EVAR, the right leg of the MK-SG was caught at the aortic bifurcation because of
      unexpected contraction of the MK-SG. To resolve the problem, the body of the MK
      SG was dilated with a balloon, slightly lifted while being gradually shortened,
      and eventually successfully connected to the leg of the MK-SG. Made of nitinol
      mesh, the MK-SG is stable and flexible enough to make it one of the best stent
      grafts for EVAR. A serious drawback, however, is the high contraction rate of the
      MK-SG itself. It is difficult to estimate the appropriate length of the stent
      graft owing to unpredictable contraction. It is important to understand its
      characteristics and to carefully design and acquire sufficient skills in
      manipulating MK-SG.

PMID- 17541518
TI  - Adnexal torsion of mature cystic teratoma with hemorrhagic infarction: helpful
      findings on successive plain abdominal radiographs.
AB  - Adnexal torsion is a relatively rare cause of lower abdominal pain in women, but
      in many cases it leads to a serious condition. We present a case of adnexal
      torsion of a mature cystic teratoma in which hemorrhagic infarction was reflected
      by progressive enlargement and wall thickening on successive plain abdominal
      radiographs. There has been no other report describing such changes of adnexal
      torsion on plain abdominal radiographs.

PMID- 17541519
TI  - Postmortem computed tomography and magnetic resonance imaging in a case of
      terminal-stage small cell lung cancer: an experience of autopsy imaging in tumor
      related death.
AB  - We report a case of terminal-stage small-cell lung cancer with multiple
      metastases in which postmortem computed tomography and magnetic resonance imaging
      (collectively called "autopsy imaging") were performed and correlated with
      conventional autopsy findings. In this case, autopsy imaging provided
      contemporaneous data that supported conventional autopsy findings. Autopsy
      imaging revealed the process of primary tumor growth, changes in metastatic
      lesions, and occurrences of new metastases in the terminal stage and made it
      easier to understand the clinical course of the patient. The usefulness of
      autopsy imaging after traumatic death, sudden death from natural causes, or
      congenital anomaly has been reported. Here, we attempted a preliminary study of
      its use in the detection of death due to tumor. Our results indicated that
      autopsy imaging provides useful information in cancer-related death and may be an
      alternative when conventional autopsy cannot be performed.

PMID- 17541520
TI  - Process engineering economics of bioethanol production.
AB  - This work presents a review of studies on the process economics of ethanol
      production from lignocellulosic materials published since 1996. Our objective was
      to identify the most costly process steps and the impact of various parameters on
      the final production cost, e.g. plant capacity, raw material cost, and overall
      product yield, as well as process configuration. The variation in estimated
      ethanol production cost is considerable, ranging from about 0.13 to 0.81 US$ per
      liter ethanol. This can be explained to a large extent by actual process
      differences and variations in the assumptions underlying the techno-economic
      evaluations. The most important parameters for the economic outcome are the
      feedstock cost, which varied between 30 and 90 US$ per metric ton in the papers
      studied, and the plant capacity, which influences the capital cost. To reduce the
      ethanol production cost it is necessary to reach high ethanol yields, as well as
      a high ethanol concentration during fermentation, to be able to decrease the
      energy required for distillation and other downstream process steps. Improved
      pretreatment methods, enhanced enzymatic hydrolysis with cheaper and more
      effective enzymes, as well as improved fermentation systems present major
      research challenges if we are to make lignocellulose-based ethanol production
      competitive with sugar- and starch-based ethanol. Process integration, either
      internally or externally with other types of plants, e.g. heat and power plants,
      also offers a way of reducing the final ethanol production cost.

PMID- 17541522
TI  - [Acute subglottic tracheal stenosis after resuscitation].
AB  - Following cardiac arrest a 41-year-old patient was resuscitated for 40 min and
      required mechanical ventilation for 27.5 h. Acute shortness of breath and
      inspiratory stridor developed 7 days after successful extubation. Bronchoscopy
      revealed a subtotal tracheal stenosis caused by extensive fibrinous membranes.
      Local ischaemia caused by cuff pressure seems to be a likely explanation with an
      additional component of general hypoperfusion and haemodynamic instability which
      led to gastric bleeding (classification according to Forrest IIc) from ischaemic
      ulcers.

PMID- 17541524
TI  - [Status of the automated external defibrillators in Germany. Implementation of
      the new guidelines for resuscitation].

PMID- 17541523
TI  - [Perioperative therapy with antiplatelet agents].
AB  - Antiplatelet therapy is used to prevent thromboembolic complications in patients
      with artherothrombotic disease. In clinical routine an assessment of the risk of
      perioperative bleeding must be weighed against the risk of thromboembolic
      complications in the event of discontinuation of antiplatelet agents. The
      indications as well as the timepoint for the termination of antiplatelet therapy
      are important issues to consider. The premature interruption of oral antiplatelet
      therapy with recovery of platelet function may lead to recurrence of
      thromboembolic events. Especially patients with intracoronary stents are at
      threat when the dual platelet therapy is interrupted before complete
      endothelialization of the stent.

PMID- 17541525
TI  - [Treatment of pneumothorax].
AB  - Pneumothorax is defined as air in the pleural space, i.e. between the lung and
      the chest wall. Primary pneumothoraces (PSP) arise in otherwise healthy people
      without any lung disease. Secondary pneumothoraces (SSP) arise in subjects with
      underlying lung disease. Observation alone is recommended only in patients with
      small primary or secondary pneumothoraces of less than 1 cm depth or isolated
      apical pneumothoraces in asymptomatic patients. In symptomatic patients
      observation alone is inappropriate and active intervention is required. Although
      simple aspiration may be an option for first-line treatment in clinically stable
      patients with PSP, intercostal tube drainage is strongly recommended in all
      primary and secondary pneumothoraces requiring intervention. There are two
      objectives in the surgical management of pneumothorax. The first widely accepted
      objective is resection of blebs or the suture of apical perforations to treat the
      underlying defect. The second objective is to create a pleural symphysis to
      prevent recurrence. While video-assisted thoracic surgery may be the preferred
      surgical procedure for young, fit people with complicated or recurrent primary
      pneumothoraces, it is less reliable in cases of secondary pneumothorax. For the
      latter, open thoracotomy and repair is still the recommended approach.

PMID- 17541526
TI  - ["Humane high performance medicine - medicine for the whole person." 113th
      Congress of the German Society for Internal Medicine, Wiesbaden 14-18 April
      2007].

PMID- 17541528
TI  - [Blood glucose control in type 2 diabetes. Basic requirements for reducing
      vascular complications].
AB  - Patients with type 2 diabetes are at high risk for the development of micro- and
      macrovascular complications. It is necessary to aim at an early, multifactorial
      intervention at different levels of metabolic syndrome. Epidemiological data have
      consistently shown that postprandial hyperglycaemia has strong proatherogenic
      effects, increasing overall cardiovascular risk. These findings indicate that
      intensive blood glucose control with the aim of maintaining near normal
      preprandial (<110 mg/dl) and postprandial levels (<140 mg/dl) is required to
      minimise the incidence of complications. Antidiabetic therapy should be selected
      individually by integrating therapeutic goals and the patient's possibilities for
      self-management. The fact that national recommendations for the treatment of
      patients with type 2 diabetes are not fully implemented in clinical practice
      emphasizes the importance of further activities to improve the quality of care.

PMID- 17541529
TI  - [New concepts in the treatment of type 2 diabetes].
AB  - The development of a variety of new substances will considerably expand the
      therapeutic choices in the treatment of type 2 diabetes. In 2006, the
      endocannabinoid receptor blocker Rimonabant has been approved for the treatment
      of type 2 diabetes in Germany. This compound has led to significant reductions of
      body weight along with improvements of HbA1c levels and lipid profiles, but the
      lack of health insurance coverage limits its large scale use in germany. In April
      2007, the first members of the GLP 1 analogues/incretin mimetics (exenatide,
      Byetta) and DPP 4 inhbitors (sitagliptin, Januvia) have become available for the
      treatment of type 2 diabetes in Germany. Both drugs have significantly lowered
      HbA1c levels in clinical studies. In addition, the incretin mimetics have caused
      a progressive reduction of body weight, while the DPP 4 inhibitors have been
      rather weight neutral. Sitagliptin can be administered orally, whereas exenatide
      has to be injected subcutaneously. Neither the DPP 4 inhibitors, nor the incretin
      mimetics have led to the development of hypoglycaemia, unless combined with
      sulfonylureas. Overall, the introduction of these new drug classes will certainly
      broaden our therapeutic choices in the management of type 2 diabetes. The long
      term effects of these drugs on the development of diabetic complications in long
      term trials remains to be awaited.

PMID- 17541530
TI  - [Gene-environment interactions in the pathogenesis and prevention of type 2
      diabetes mellitus].
AB  - Type 2 diabetes mellitus is a chronic progressive disease characterized by
      impaired insulin secretion of the beta cell and impaired insulin sensitivity of
      different tissues. The incidence of type 2 diabetes mellitus is increasing
      worldwide, and the disease has reached epidemic proportions. Lifestyle
      intervention programs are able to delay or possibly prevent the manifestation of
      type 2 diabetes mellitus. This review summarizes the genetic and environmental
      factors which influence the risk for type 2 diabetes and their interactions, and
      determine the success of prevention programs.

PMID- 17541531
TI  - [Acute febrile disease with splenomegaly and pancytopenia. A 66-year-old Greek
      patient with a prosthetic mitral valve].
AB  - We report on a 66-year-old patient originating from Greece and living in Germany
      with a prosthetic mitral valve because of a combined vitium following juvenile
      rheumatic fever. The patient fell ill with acute fever, splenomegaly, and
      pancytopenia. After unsuccessful antibiotic therapy because of presumed
      endocarditis or sepsis with unknown focus, visceral leishmaniasis was suspected
      because of recent travel to Greece. Subsequently, this diagnosis was confirmed by
      serology. Considering thrombocytopenia and concurrent anticoagulation after
      prosthetic mitral valve replacement, we avoided a bone marrow biopsy usually
      required for definite proof of leishmania infection. Instead, infection with
      Leishmania infantum was diagnosed by PCR of a peripheral blood sample. After
      treatment with liposomal amphotericin B the patient recovered fully.

PMID- 17541532
TI  - [Sepsis-like disease in an immunocompromised patient with a travel history to
      Mallorca].
AB  - In immunosuppressed patients, a high rate of complications due to opportunistic
      infection is known. We report the case of a 36 year old patient with ulcerative
      colitis and a septic complication with ongoing pancytopenia. Due to colonic
      perforation, colectomy had to be performed. Despite this intervention, the septic
      constellation persisted. The pancytopenia in peripheral blood counts also
      persisted with the necessity of repetitive transfusions. A bone marrow biopsy
      showed an infiltration with Leishmania bodies in macrophages. Tissue culture
      allowed for typing of the parasites as belonging to the L. donovani/infantum
      complex, DNA sequencing confirmed infection with L. infantum. This infection must
      have been contracted during a vacation on Mallorca about 1.5 years earlier.
      Administration of liposomal amphotericin B cured the patient. Surprisingly,
      histological examination of the resected colon reveiled the presence of an
      immunoblastic B-cell lymphoma. In this case, immunosuppression was a prerequisite
      for the manifestation of leishmaniosis.

PMID- 17541533
TI  - [Indications for an implantable cardioverter/defibrillator].
AB  - The implantable cardioverter/defibrillator (ICD), which uses antitachycardia
      pacing or shock, is the only adequate therapeutic option for life threatening
      ventricular tachyarrhythmias. The results of prospective, randomised ICD trials
      show that the indications for primary and secondary prevention of sudden cardiac
      death have changed in a relevant manner. After the identification of a patient at
      risk, the implantation of an ICD reduces cardiac and total mortality
      significantly. A clear diagnostic procedure and the parameters needed for the
      identification of this risk are essential. We report on the indications for the
      implantation of an ICD following current guidelines in order to enable the
      physician to provide his patients with an adequate ICD therapy in everyday
      practice.

PMID- 17541534
TI  - The immunity of splenic and peritoneal F4/80(+) resident macrophages in mouse
      mixed allogeneic chimeras.
AB  - Mixed allogeneic chimeras are emerging as a prospective approach to induce immune
      tolerance in clinics. However, the immunological function of macrophages in mixed
      chimeras has not been evaluated. Using a B6-->BALB/c mixed chimera model, we
      investigated the phenotype and function of F4/80(+) resident peritoneal exudate
      macrophage (PEMs) and splenic macrophages (SPMs) in vitro and in vivo. Recipient
      F4/80(+)PEMs and SPMs in mixed chimeras expressed significantly lower levels of
      MHC-II, CD54, and CD23 than those in non-chimeric mice before lipopolysaccharide
      stimulation. Recipient F4/80(+)PEMs and SPMs in mixed chimeras induced normal
      cell proliferation and delayed-type hypersensitivity of allo-T cells, but they
      induced more IFN-gamma and IL-2 products and less IL-10 and TGF-beta products of
      allo-T cells compared with those of non-chimeras. Furthermore, recipient
      F4/80(+)PEMs and SPMs had significantly higher phagocytotic capacity against
      chicken red blood cells or allo-T cells than those of controls while they had
      normal phagocytosis to Escherichia coli. Although some slight but significant
      alterations of recipient macrophages have been detected, these results provide
      direct evidences for the efficient immunity of recipient macrophages in mixed
      allogeneic chimeras. The present study also, for the first time, offered basic
      information for macrophages maturing in heterogeneous environments.

PMID- 17541535
TI  - Soil and preen waxes influence the expression of carotenoid-based plumage
      coloration.
AB  - The signaling function of carotenoid-based plumage is mainly determined by the
      concentration of pigments in feathers. For this reason, most studies of the
      proximate control of coloration focus on processes during and preceding moult. In
      great tits Parus major, past research demonstrates that carotenoid-based plumage
      coloration honestly indicates male quality and, thus, may be a sexually selected
      signal. In this study, we investigate how dirt and preen oil influence the
      coloration of carotenoid-based feathers in the great tit. We collected six
      feathers from each individual bird; three feathers served as controls while the
      remaining three feathers were washed with a chloroform/methanol mixture to remove
      soil and preen waxes. We assessed plumage coloration using digital photography.
      This cleaning procedure slightly enhanced ornamentation; the experimentally
      cleaned feathers expressed hues shifted towards shorter wavelengths and expressed
      brighter overall coloration than control feathers. This is the first experimental
      study conducted on wild birds demonstrating that, in addition to pigment
      concentration, the presence of preen waxes and soils on feathers may contribute
      to variation in coloration.

PMID- 17541536
TI  - Non-specific association between filamentous bacteria and fungus-growing ants.
AB  - Fungus-growing ants and their fungal cultivar form a highly evolved mutualism
      that is negatively affected by the specialized parasitic fungus Escovopsis.
      Filamentous Pseudonocardia bacteria occurring on the cuticle of attine ants have
      been proposed to form a mutualistic interaction with these ants in which they are
      vertically transmitted (i.e. from parent to offspring colonies). Given a strictly
      vertical transmission of Pseudonocardia, the evolutionary theory predicts a
      reduced genetic variability of symbionts among ant lineages. The aim of this
      study was to verify whether actinomycetes, which occur on Acromyrmex octospinosus
      leaf-cutting ants, meet this expectation by comparing their genotypic variability
      with restriction fragment length polymorphisms. Multiple actinomycete strains
      could be isolated from both individual ant workers and colonies (one to seven
      strains per colony). The colony specificity of actinomycete communities was high:
      Only 15% of all strains were isolated from more than one colony, and just 5% were
      present in both populations investigated. Partial sequencing of 16S ribosomal
      deoxyribonucleic acid of two of the isolated strains assigned both of them to the
      genus Streptomyces. Actinomycetes could also be isolated from workers of the two
      non-attine ant species Myrmica rugulosa and Lasius flavus. Sixty-two percent of
      the strains derived from attine ants and 80% of the strains isolated from non
      attine ants inhibited the growth of Escovopsis. Our data suggest that the
      association between attine ants and their actinomycete symbionts is less specific
      then previously thought. Soil-dwelling actinomycetes may have been dynamically
      recruited from the environment (horizontal transmission), probably reflecting an
      adaptation to a diverse community of microbial pathogens.

PMID- 17541537
TI  - The parthenogenetic Marmorkrebs (marbled crayfish) produces genetically uniform
      offspring.
AB  - Genetically identical animals are very much in demand as laboratory objects
      because they allow conclusions about environmental and epigenetic effects on
      development, structures, and behavior. Furthermore, questions about the relative
      fitness of various genotypes can be addressed. However, genetically identical
      animals are relatively rare, in particular, organisms that combine a high
      reproduction rate and a complex organization. Based on its exclusively
      parthenogenetic reproduction mode, it has been suggested that the Marmorkrebs
      (Crustacea, Decapoda, Astacida), a recently discovered crayfish, is an excellent
      candidate for research addressing the aforementioned questions. However, until
      now, a study using molecular markers that clearly proves the genetic uniformity
      of the offspring has been lacking. Here, with this first molecular study, we show
      that this crayfish indeed produces genetically uniform clones. We tested this
      with 19 related individuals of various generations of a Marmorkrebs population by
      means of six different microsatellite markers. We found that all examined
      specimens were identical in their allelic composition. Furthermore, half of the
      analyzed loci were heterozygous. These results and the absence of meioses in
      previous histological studies of the ovaries lead us to conclude the Marmorkrebs
      propagates apomictically. Thus, a genetically uniform organism with complex
      morphology, development, and behavior is now available for various laboratory
      studies.

PMID- 17541538
TI  - [Supratentorial tumors].
AB  - Magnetic resonance imaging is a routine diagnostic measure for a suspected
      intracerebral mass. Computed tomography is usually also indicated. Further
      diagnostic procedures as well as the interpretation of the findings vary
      depending on the tumor location. This contribution discusses the symptoms and
      diagnostics for supratentorial tumors separated in relation to their intra- or
      extracranial location. Supratentorial tumors include astrocytoma, differentiated
      by their circumscribed and diffuse growth, ganglioglioma, ependyoma, neurocytoma,
      primitive neuroectodermal tumors (PNET), oligodendroglioma, dysem-bryoplastic
      neuroepithelial tumors (DNET), meningoangiomatosis, pineal tumors, hamatoma,
      lymphoma, craniopharyngeoma and metastases. The supratentorial extracranial
      tumors include the choroid plexus, colloid cysts, meningeoma, infantile
      myofibromatosis and lipoma. The most common sub-forms, especially of astrocytoma,
      will also be presented.

PMID- 17541539
TI  - [Singular ileum interposition with bilateral implantation of the ureters after
      Wertheim-Meigs surgery].
AB  - Ileum or colon interpositions are qualified procedures for functional ureteral
      replacement in case of extended ureteric lesions. In most cases, a unilateral
      interposition is sufficient. Rarely, it is necessary to perform bilateral
      procedures. We report the case of a 41-year-old female patient with bilateral
      ureter implantation into a singular ileum segment.

PMID- 17541540
TI  - Meta-analysis of the effects of n-3 polyunsaturated fatty acids on lipoproteins
      and other emerging lipid cardiovascular risk markers in patients with type 2
      diabetes.
AB  - AIMS/HYPOTHESIS: To determine the effects of marine-derived n-3 polyunsaturated
      fatty acids (PUFA) on established and emerging lipid and lipoprotein
      cardiovascular risk markers in patients with type 2 diabetes. MATERIALS AND
      METHODS: We performed a systematic review and meta-analysis of randomised
      controlled trials comparing dietary or non-dietary intake of n-3 PUFA with
      placebo in patients with type 2 diabetes by searching databases from 1966 to
      December 2006. Changes in the following variables were recorded triacylglycerol;
      total cholesterol; HDL, LDL and VLDL and their subfractions; lipid ratios;
      apolipoproteins; and cholesterol particle sizes. RESULTS: There were 23 trials on
      non-dietary supplementation, involving 1,075 subjects with a mean treatment
      duration of 8.9 weeks, with sufficient data to permit pooling. Compared with
      placebo, n-3 PUFA had a statistically significant effect on four outcomes,
      reducing levels of (1) triacylglycerol (18 trials, 969 subjects) by 25% (mean
      0.45 mmol/l; 95% CI -0.58 to -0.32; p < 0.00001); (2) VLDL-cholesterol (7 trials,
      238 subjects) by 36% (0.07 mmol/l; 95% CI -0.13 to 0.00; p = 0.04); and (3) VLDL
      triacylglycerol (6 trials, 178 subjects) by 39.7% (0.44 mmol/l; 95% CI -0.83 to 
      0.05; p = 0.03); while slightly increasing LDL (16 trials, 565 subjects) by 5.7%
      (0.11 mmol/l; 95% CI 0.00 to 0.22; p = 0.05). There were no significant effects
      on total cholesterol, apolipoproteins, lipid subfractions or ratios.
      CONCLUSIONS/INTERPRETATION: In addition to recognised triacylglycerol-lowering
      effects, n-3 PUFA supplementation decreases VLDL-cholesterol and VLDL
      triacylglycerol, but may have an adverse effect on LDL-cholesterol. Larger and
      longer term clinical trials are required to conclusively establish the effect of
      n-3 PUFA on cardiovascular risk markers and outcomes in type 2 diabetic patients.

PMID- 17541541
TI  - [Irritation of the iliopsoas tendon after total hip arthroplasty].
AB  - Chronic irritation of the iliopsoas tendon is a rare cause of persistent pain
      after total joint replacement of the hip. In the majority of cases, pain results
      from a mechanical conflict between the iliopsoas tendon and the anterior edge of
      the acetabular cup after total hip arthroplasty. Pain can be reproduced by active
      flexion of the hip and by active raising of the straightened leg. In addition,
      painful leg raising against resistance and passive hyperextension are suggestive
      of an irritation of the iliopsoas tendon. Symptoms evolve from a mechanical
      irritation of the iliopsoas tendon and an oversized or retroverted acetabular
      cup, screws penetrating into the inner aspect of the ilium, or from bone cement
      protruding beyond the anterior acetabular rim. The diagnosis may be assumed on
      conventional radiographs and confirmed by CT scans. Fifteen patients with psoas
      irritation after total hip replacement are reported on. Eleven patients were
      treated surgically. The acetabular cup was revised and reoriented with more
      anteversion in six patients, isolated screws penetrating into the tendon were cut
      and leveled in three patients, and prominent bone cement in conflict with the
      tendon was resected once. A partial release of the iliopsoas tendon only was
      performed in another patient. Follow-up examination (range: 11-89 months)
      revealed that nine patients were free of pain and two patient had mild residual
      complaints. Psoas irritation in combination with total hip replacement can be
      prevented by a correct surgical technique, especially with proper selection of
      the cup size and insertion of the acetabular cup avoiding a rim position
      exceeding the level of the anterior acetabular rim.

PMID- 17541542
TI  - B-type natriuretic peptide as a marker for heart failure in patients with acute
      stroke.
AB  - OBJECTIVE: To determine whether serum N-terminal pro-B-type natriuretic peptide
      (N-BNP), a biomarker of myocardial wall stress, is specific to acute heart
      failure (HF) in patients hospitalized with stroke. DESIGN: Case-control study.
      SETTING: Tertiary hospital, Neurosciences Critical Care Unit and Stroke Unit.
      PATIENTS: Consecutive patients with acute ischemic or hemorrhagic stroke who were
      evaluated for HF. INTERVENTION: None. MEASUREMENTS AND RESULTS: Cases and
      controls were classified, respectively, as patients with or without HF, defined
      according to modified Framingham criteria. Seventy-two patients were evaluated,
      39 with ischemic stroke, 22 with aneurysmal subarachnoid hemorrhage (SAH), and 11
      with intracerebral hemorrhage (ICH). Thirty-four patients (47%) met criteria for
      HF, and 47 patients (65%) had systolic or diastolic left ventricular (LV)
      dysfunction on echocardiogram. Serum N-BNP was measured a median of 48 h
      following the onset of stroke and was increased (> 900 pg/ml) in 56 patients
      (78%), with higher levels in non-survivors (11898 +/- 12741 vs 4073 +/-5691; p =
      0.001). In a multiple regression model, N-BNP elevation was not independently
      associated with HF (OR 5.4, 95% CI 0.8-36.0, p = 0.084). At a cut-off of 900
      pg/ml, the sensitivity of N-BNP for HF was 94%, specificity 37%, positive
      predictive value (PPV) 57%, and negative predictive value (NPV) 88%. For systolic
      or diastolic LV dysfunction, the sensitivity of N-BNP was 89%, specificity 44%,
      PPV 75%, and NPV 69%. CONCLUSIONS: These results demonstrate that N-BNP elevation
      is not specific to HF or LV dysfunction in patients with acute ischemic stroke,
      SAH, and ICH.

PMID- 17541544
TI  - Not using data of patients who die before deferred informed consent potentially
      jeopardises emergency medical trials.

PMID- 17541545
TI  - Management of 350 aneurysmal subarachnoid hemorrhages in 22 Italian neurosurgical
      centers.
AB  - OBJECTIVE: To collect information on clinical practice and current management
      strategies in 22 Italian neurosurgical hospitals for patients with aneurysmal
      subarachnoid hemorrhage. DESIGN AND SETTING: Observational 6-month study for
      prospective data collection. PATIENTS: 350 cases of aneurysmal subarachnoid
      hemorrhage. MEASUREMENTS AND RESULTS: Each center enrolled from 4-36 patients.
      Neurological deterioration (24%) was more frequent in patients with higher Fisher
      classification, and with pretreatment rebleeding and it was associated with an
      unfavorable outcome (46%, 36/78, vs. 33%, 83/251). Aneurysms were mainly secured
      by clipping (55%, 191/350). An endovascular approach was utilized in 35%
      (121/350). The more frequent medical complications were fever, recorded in one
      half of cases, pneumonia (18%), sodium disturbances (hyponatremia 22%,
      hypernatremia 17%), cardiopulmonary events as neurogenic pulmonary edema (4%) and
      myocardial ischemia (5%). Intracranial hypertension was experienced in one-third
      of the patients, followed by hydrocephalus (29%) and vasospasm (30%). Cerebral
      ischemia was found in an about one-quarter of the cohort. To identify the
      independent predictors of outcome we developed a model in which the dichotomized
      Glasgow Outcome Scale was tested as function of extracranial and intracranial
      complications. Only high intracranial pressure and deterioration in neurological
      status were independent factors related to unfavorable outcome. CONCLUSIONS: Our
      data confirm that in every step of care there is extreme heterogeneity among
      centers. These patients are complex, with comorbidities, immediate risk of
      rebleeding, and delayed risk of intracranial and medical complications. Following
      SAH early treatment and careful intensive care management requires the careful
      coordination of the various clinical specialties.

PMID- 17541546
TI  - Adrenal response in children with septic shock.
AB  - OBJECTIVE: To describe the serum cortisol profile and evaluate the adrenal
      response in children with septic shock, and determine the influence of these
      factors on the outcome and mortality in this group. METHODS: Between May and
      November 2003, 22 children with septic shock admitted to two pediatric intensive
      care units in southern Brazil were followed. Adrenal function was evaluated based
      on the levels of cortisol measured on the occasion of the diagnosis of septic
      shock and on the response of serum cortisol 30 min after the administration of
      intravenous corticotrophin (0.5 microg/1.73m(2)). Adrenal insufficiency was
      defined as a baseline serum cortisol below 690 nmol/l and/or a cortisol response
      to corticotrophin less than 250 nmol/l. RESULTS: Adrenal insufficiency was
      detected in 17 patients (77.3%). All patients who died had baseline cortisol
      higher than 690 nmol/l. A cortisol response to corticotrophin less than 250
      nmol/l was associated with a 60% mortality (RR = 7.2, 1.03-50.28). Regression
      analysis showed that the combination of baseline cortisol higher than 690 nmol/l
      and a cortisol response to corticotrophin less than 250 nmol/l were associated
      with mortality after correction for gender and PRISM. CONCLUSIONS: Adrenal
      insufficiency is a frequent finding in children with septic shock. The low-dose
      corticotrophin stimulation test seems to be an important tool to distinguish
      between a normal cortisol response to stress and evidence of adrenal failure.
      Mortality was significantly higher in children that failed to respond to a
      corticotrophin stimulation test.

PMID- 17541547
TI  - ICUs: from performance appraisal to executive dashboard?

PMID- 17541548
TI  - Withdrawal symptoms in children after long-term administration of sedatives
      and/or analgesics: a literature review. "Assessment remains troublesome".
AB  - BACKGROUND: Prolonged administration of benzodiazepines and/or opioids to
      children in a pediatric intensive care unit (PICU) may induce physiological
      dependence and withdrawal symptoms. OBJECTIVE: We reviewed the literature for
      relevant contributions on the nature of these withdrawal symptoms and on
      availability of valid scoring systems to assess the extent of symptoms. METHODS:
      The databases PubMed, CINAHL, and Psychinfo (1980-June 2006) were searched using
      relevant key terms. RESULTS: Symptoms of benzodiazepine and opioid withdrawal can
      be classified in two groups: central nervous system effects and autonomic
      dysfunction. However, symptoms of the two types show a large overlap for
      benzodiazepine and opioid withdrawal. Symptoms of gastrointestinal dysfunction in
      the PICU population have been described for opioid withdrawal only. Six
      assessment tools for withdrawal symptoms are used in children. Four of these have
      been validated for neonates only. Two instruments are available to specifically
      determine withdrawal symptoms in the PICU: the Sedation Withdrawal Score (SWS)
      and the Opioid Benzodiazepine Withdrawal Scale (OBWS). The OBWS is the only
      available assessment tool with prospective validation; however, the sensitivity
      is low. CONCLUSIONS: Withdrawal symptoms for benzodiazepines and opioids largely
      overlap. A sufficiently sensitive instrument for assessing withdrawal symptoms in
      PICU patients needs to be developed.

PMID- 17541549
TI  - Increased mortality in septic shock with the 4G/4G genotype of plasminogen
      activator inhibitor 1 in patients of white descent.
AB  - OBJECTIVE: To evaluate the effect of the 4G/5G PAI-1 gene polymorphism on the
      development of organ failure and outcome in critically ill patients with septic
      syndromes. DESIGN AND SETTING: Prospective, observational study in a medical
      intensive care unit of a university hospital. PATIENTS: 224 consecutively
      admitted patients. INTERVENTIONS: Epidemiological data, severity scores, and the
      primary site of infection were recorded. DNA genotyping of the PAI-1, TNF-beta,
      and IL1-ra genes, and measurement of plasma PAI-1 antigen and D-dimer were
      carried out. MEASUREMENTS: The primary outcome variables were organ dysfunction
      and mortality. RESULTS: Eighty-eight subjects had septic shock at ICU entry or
      within 48 h from admission. Homozygotes for the 4G allele exhibited higher plasma
      concentrations of PAI-1 antigen and D-dimer than 4G/5G and 5G/5G subjects). ICU
      mortality was 44.0% in patients with 4G/4G, 23.4% in 4G/5G and 12.5% in 5G/5G,
      mainly due to multiorgan failure. After adjusting for SAPS II at admission the
      genotypes independently associated with ICU mortality in septic shock were TNF
      B2/B2 (OR 2.83, 1.04-7.67) and 4G/4G of PAI-1 (OR 2.23, 1.02-4.85). The PAI-1
      genotype did not determine susceptibility to infection or the outcome in
      nonseptic systemic inflammatory response syndrome, sepsis, severe sepsis, and
      nosocomial septic shock. CONCLUSIONS: Homozygosity for 4G of the PAI-1 gene
      confers an increase in the risk of mortality in adult patients with septic shock
      due to a greater organ failure.

PMID- 17541550
TI  - The importance of religious affiliation and culture on end-of-life decisions in
      European intensive care units.
AB  - OBJECTIVE: To determine the influence of religious affiliation and culture on end
      of-life decisions in European intensive care units (ICUs). DESIGN AND SETTING: A
      prospective, observational study of European ICUs was performed on consecutive
      patients with any limitation of therapy. Prospectively defined end-of-life
      practices in 37 ICUs in 17 European countries studied from 1 January 1999 to 30
      June 2000 were compared for frequencies, patterns, timing, and communication by
      religious affiliation of physicians and patients and regions. RESULTS: Of the
      31,417 patients 3,086 had limitations. Withholding occurred more often than
      withdrawing if the physician was Jewish (81%), Greek Orthodox (78%), or Moslem
      (63%). Withdrawing occurred more often for physicians who were Catholic (53%),
      Protestant (49%), or had no religious affiliation (47%). End-of-life decisions
      differed for physicians between regions and who had any religious affiliation vs.
      no religious affiliation in all three geographical regions. Median time from ICU
      admission to first limitation of therapy was 3.2 days but varied by religious
      affiliation; from 1.6 days for Protestant to 7.6 days for Greek Orthodox
      physicians. Median times from limitations to death also varied by physician's
      religious affiliation. Decisions were discussed with the families more often if
      the physician was Protestant (80%), Catholic (70%), had no religious affiliation
      (66%) or was Jewish (63%). CONCLUSIONS: Significant differences associated with
      religious affiliation and culture were observed for the type of end of life
      decision, the times to therapy limitation and death, and discussion of decisions
      with patient families.

PMID- 17541551
TI  - Comparison of lung injury after normal or small volume optimized resuscitation in
      a model of hemorrhagic shock.
AB  - OBJECTIVE: To compare lung injury induced by a hemorrhagic shock resuscitated
      with normal saline or with small volumes of a hypertonic/hyperoncotic solution.
      DESIGN AND SETTING: Randomized, controlled, laboratory study in an animal
      research laboratory. SUBJECTS: Nineteen pigs (43 +/- 4 kg). INTERVENTIONS: After
      anesthesia and mechanical ventilation animals were bled to induce a 2-h deep
      shock and resuscitated for 2 h using normal saline (NS, 2 ml/kg per minute, n =
      7) or the association of 7.2% NaCl with 6% hydroxyethylstarch 200/0.5 (HSHES, 4
      ml/kg in 10 min followed by 0.2 ml/kg per minute, n = 7) to reach cardiac index
      and mixed venous oxygen saturation goals. Lungs were removed 6[Symbol: see text]h
      after the initiation of hemorrhage. Five animals were used as controls without
      hemorrhage. MEASUREMENTS AND RESULTS: Resuscitation goals were achieved using 90
      +/- 17 ml/kg NS or 6.8 +/- 1.9 ml/kg HSHES. Lung injury was noted in both
      hemorrhage groups but was not influenced by the type of resuscitation.
      Extravascular lung water was measured at 9.6 +/- 1.8 ml/kg in the NS group, 9.2
      +/- 1.6 ml/kg in the HSHES, group and 6.4 +/- 1 m/kg in the control group. The
      degree of histological alveolar membrane focal thickening and interstitial
      neutrophil infiltration were significantly more pronounced in the hemorrhage
      groups with no difference between the two types of fluid loading. Finally,
      pulmonary levels of IL-8 were higher after hemorrhage regardless of the type of
      resuscitation. CONCLUSIONS: When included in an optimized and goal directed
      resuscitation, the use of normal saline or a small volume of
      hypertonic/hyperoncotic solution does not result in a different early hemorrhage
      induced lung injury.

PMID- 17541552
TI  - Variability in outcome and resource use in intensive care units.
AB  - OBJECTIVE: To examine variability in outcome and resource use between ICUs.
      Secondary aims: to assess whether outcome and resource use are related to ICU
      structure and process, to explore factors associated with efficient resource use.
      DESIGN AND SETTING: Cohort study, based on the SAPS 3 database in 275 ICUs
      worldwide. PATIENTS: 16,560 adults. MEASUREMENTS AND RESULTS: Outcome was defined
      by standardized mortality rate (SMR). Standardized resource use (SRU) was
      calculated based on length of stay in the ICU, adjusted for severity of acute
      illness. Each unit was assigned to one of four groups: "most efficient" (SMR and
      SRU < median); "least efficient" (SMR, SRU > median); "overachieving" (low SMR,
      high SRU), "underachieving" (high SMR, low SRU). Univariate analysis and stepwise
      logistic regression were used to test for factors separating "most" from "least
      efficient" units. Overall median SMR was 1.00 (IQR 0.77-1.28) and SRU 1.07 (0.76
      1.58). There were 91 "most efficient", 91 "least efficient", 47 "overachieving",
      and 46 "underachieving" ICUs. Number of physicians, of full-time specialists, and
      of nurses per bed, clinical rounds, availability of physicians, presence of
      emergency department, and geographical region were significant in univariate
      analysis. In multivariate analysis only interprofessional rounds, emergency
      department, and geographical region entered the model as significant.
      CONCLUSIONS: Despite considerable variability in outcome and resource use only
      few factors of ICU structure and process were associated with efficient use of
      ICU. This suggests that other confounding factors play an important role.

PMID- 17541553
TI  - Association of cell-free plasma DNA with hospital mortality and organ dysfunction
      in intensive care unit patients.
AB  - OBJECTIVE: To investigate the concentration of cell-free plasma DNA and its
      association with organ dysfunction and hospital mortality in intensive care unit
      patients. DESIGN AND SETTING: Prospective cohort study in a medical and two
      medical-surgical intensive care units in a university hospital. PATIENTS: 228
      critically ill patients admitted to the ICUs between January 2004 and July 2005.
      MEASUREMENTS AND RESULTS: Blood samples were collected as soon as possible after
      ICU admission, the following morning, and 48[Symbol: see text]h after the second
      sample. The cell-free plasma DNA was measured by real-time quantitative PCR assay
      for the beta-globin gene. Physiological and mortality data were collected to the
      clinical database. Hospital mortality rate and SOFA scores were primary outcome
      measures. The maximum plasma DNA concentrations were correlated significantly
      with APACHE II points and with maximum SOFA scores. Cell-free plasma DNA
      concentrations were higher in hospital non-survivors than in survivors (median
      9,366 vs. 6,506 GE/ml). Using logistic regression analysis, the maximum plasma
      DNA was an independent predictor of hospital mortality. CONCLUSIONS: The maximum
      plasma DNA concentration measured during the first 96[Symbol: see text]h of
      intensive care is associated with the degree of organ dysfunction and disease
      severity. Moreover, the maximum DNA concentration is independently associated
      with hospital mortality.

PMID- 17541554
TI  - A method for monitoring and improving patient: ventilator interaction.
AB  - OBJECTIVE: To evaluate a new approach for monitoring and improving patient
      ventilator interaction that utilizes a signal generated by the equation of
      motion, using improvised values for resistance and elastance obtained
      noninvasively. DESIGN AND SETTING: Observational study in intensive care units in
      five European centers. PATIENTS: We studied 21 stable patients instrumented with
      esophageal/gastric catheters for a previous study and ventilated alternately with
      pressure support (PSV) and proportional assist (PAV) ventilation with a Tyco 840
      ventilator. MEASUREMENTS AND RESULTS: Previously recorded digital files were
      analyzed in real-time by a prototype incorporating the new technology (PVI
      monitor, YRT, Winnipeg, Canada). Actual onsets (P(DI)-T(ONSET)) and ends (P(DI)
      T(END)) of inspiratory efforts, ineffective efforts, and patient respiratory rate
      were identified visually from transdiaphragmatic or calculated respiratory muscle
      pressure. Monitor-identified T(ONSET) occurred 0.107 +/- 0.074 s after P(DI)
      T(ONSET), substantially less than trigger delay observed with conventional
      triggering (0.326 +/- 0.086 s). End of effort was identified 0.097 +/- 0.096 s
      after P(DI)-T(END), significantly less than actual cycling-off delay during PSV
      (0.486 +/- 0.307 s) or PAV (0.277 +/- 0.084 s). The monitor detected 80% of
      ineffective efforts. There was excellent agreement between monitor-estimated
      respiratory rate and actual patient rate over a wide range (17-59/min) of patient
      rates (mean (+/- SD) of difference -0.2 +/- 1.9/min for pressure support and 0.2
      +/- 0.9/min for proportional assist) even when large discrepancies existed (>
      35/min) between patient and ventilator rates. CONCLUSIONS: The proposed approach
      should make it possible to improve patient-ventilator interaction and to obtain
      accurate estimates of true patient respiratory rate when there is nonsynchrony.

PMID- 17541555
TI  - Characterization of symbiotic and endophytic bacteria isolated from root nodules
      of herbaceous legumes grown in Qinghai-Tibet plateau and in other zones of China.
AB  - Qinghai-Tibet plateau is the highest place in the world and the environment in
      that plateau is hard for animals and plants, with low temperature, low
      concentration of oxygen and high solar radiation. In this study, 61 root nodule
      isolates from Vicia, Oxytropis, Medicago, Melilotus and Onobrychis species grown
      in Qinghai-Tibet plateau and in loess plateau were comparatively characterized.
      Based upon the results of numerical taxonomy, ARDRA, AFLP, DNA-DNA hybridization
      and 16S rDNA sequencing, the isolates were classified as Rhizobium leguminosarum,
      Sinorhizobium meliloti, Sinorhizobium fredii, Mesorhizobium sp., Phyllobacterium
      sp., Stenotrophomonas sp. and two non-symbiotic groups related to Agrobacterium
      and Enterobacteriaceae. The strains isolated from Qinghai-Tibet plateau and from
      the loess plateau were mixed in these species or groups. Oxytropis spp. and
      Medicago archiducis-nicolai grown in Qinghai-Tibet plateau were recorded as new
      hosts for R. leguminosarum, as well as Oxytropis glabra and Medicago lupulina for
      S. fredii. In addition, strains resistant to high alkaline (pH 11) and high
      concentration of NaCl (3-5%, w/v) were found in each of the rhizobial species.
      This was the first systematic study of rhizobia isolated from Qinghai-Tibet
      plateau.

PMID- 17541556
TI  - Cordycepin induced eryptosis in mouse erythrocytes through a Ca2+-dependent
      pathway without caspase-3 activation.
AB  - Cordyceps sinensis is a prized traditional Chinese medicine and its major
      component cordycepin is found to have anti-leukemia activities. However, its
      cytotoxicity in erythrocytes was unclear. To examine the effect of cordycepin on
      the induction of eryptosis (an apoptosis-like process in enucleated
      erythrocytes), flow cytometric assays based on membrane integrity and asymmetry
      were employed. For comparison, analyses were performed in parallel with two other
      anti-leukemia agents, indirubin 3'-monoxime (IDM) and As2O3. We found that at the
      IC50 against leukemia HL-60, cordycepin elicited eryptosis while IDM and As2O3
      showed no erythrotoxicity in mouse erythrocytes. Mechanistically, cordycepin
      increased the [Ca2+]i and activated mu-calpain protease in a dose-dependent
      manner. Yet, no caspase-3 activation was observed in the cordycepin-treated
      erythrocytes. When extracellular Ca2+ was depleted, both the cordycepin-induced
      eryptosis and mu-calpain cleavage were suppressed. Our study therefore
      demonstrated for the first time that cordycepin induces eryptosis through a
      calcium-dependent pathway in the absence of mitochondria and caspase-3
      activation.

PMID- 17541557
TI  - In patients chronically treated with metoprolol, the demand of inotropic
      catecholamine support after coronary artery bypass grafting is determined by the
      Arg389Gly-beta 1-adrenoceptor polymorphism.
AB  - In vitro, the Arg389Gly-beta(1)-adrenoceptor (AR) polymorphism exhibits decreased
      receptor signaling. In vivo, dobutamine infusion evoked smaller heart rate and/or
      contractility increases in subjects carrying Gly389Gly-beta(1)AR vs subjects
      carrying Arg389Arg-beta(1)AR. The aim of this study was to find out whether the
      Arg389Gly-beta(1)AR polymorphism might also determine demand of catecholamine
      induced inotropic support in patients with low cardiac index (CI) after coronary
      artery bypass grafting (CABG) surgery with cardiopulmonary bypass (CPB). For this
      purpose, we assessed in 82 patients, who were preoperatively chronically treated
      with metoprolol, after CABG surgery with CPB, the dose and duration of adrenaline
      induced inotropic support in relation to the Arg389Gly-beta(1)AR genotype.
      Patients homozygous for the Arg389-beta(1)AR variant (n = 45) required, in
      comparison to patients homozygous for the Gly389-beta(1)AR variant (n = 9), lower
      adrenaline doses (53 +/- 24 vs 164 +/- 39 ng/kg body weight/min, p < 0.05) to
      reach a stable and comparable hemodynamic status and a CI >or= 3.0 l/min/m(2).
      Moreover, the time necessary for inotropic support tended to be shorter in
      patients homozygous for the Arg389-beta(1)AR than in patients homozygous for the
      Gly389-beta(1)AR (10.5 +/- 6 vs 20.5 +/- 12 h). Values for patients heterozygous
      for the Arg389Gly-beta(1)AR (n = 28) were in between. We conclude that the
      Arg389Gly-beta(1)AR polymorphism appears to be a determinant of cardiac responses
      to catecholamine stimulation. Thus, by assessment of the Arg389Gly-beta(1)AR
      polymorphism, it might be possible to predict demand of and therapeutic responses
      to beta AR agonist treatment.

PMID- 17541559
TI  - Monitoring of the surface of paper samples exposed to UV light by ATR-FT-IR
      spectroscopy and use of multivariate control charts.
AB  - The effect of exposure of paper samples to UV light was monitored by use of ATR
      FT-IR spectroscopy and multivariate statistical tools. Three types of paper were
      tested: common laser-printer paper, news print, and thermal fax paper. The
      samples were first characterised by ATR-FT-IR spectroscopy to determine natural
      experimental variability. They were then exposed to UV light for 30 h and the
      effects of the exposure were monitored by use of the same spectroscopic
      technique. Finally, multivariate statistical tools were applied to the final
      dataset, coupled with construction of multivariate control charts, to identify
      the effects of UV light on the sample surfaces.

PMID- 17541558
TI  - Acute or subchronic clozapine treatment does not ameliorate prepulse inhibition
      (PPI) deficits in CPB-K mice with low levels of hippocampal NMDA receptor
      density.
AB  - INTRODUCTION: The hypo-glutamatergic hypothesis of schizophrenia is based on
      clinical similarities between schizophrenia and phencyclidine (PCP)-induced
      psychosis in mentally healthy humans. Sensorimotor gating, as measured by
      prepulse inhibition (PPI) of the acoustic startle response (ASR), is impaired in
      schizophrenic patients. In animals, noncompetitive N-methyl-D: -aspartate (NMDA)
      antagonists such as PCP disrupt PPI in a way that resembles the defect seen in
      schizophrenia. In a previous study with inbred mouse strains, low PPI levels have
      been demonstrated in CPB-K mice possessing low levels of hippocampal NMDA
      receptor densities. The present study was performed to test whether the low
      magnitude of PPI in CPB-K mice can be reversed by the atypical antipsychotic drug
      clozapine (CLZ). RESULTS: Before any treatment, CPB-K mice displayed a
      significant (p < 0.001) lower level in PPI and a significant (p < 0.001) higher
      ASR when compared to BALB/cJ mice known to have high hippocampal NMDA receptor
      densities. Acute and subchronic effects of a 2-week treatment with CLZ at daily
      doses of 5 and 10 mg/kg intraperitoneally, respectively, did not reveal any
      significant alteration of PPI levels in CPB-K mice. Nevertheless, the examination
      of motor behavior during nonstimulus trials provided a positive control for the
      drug's effectiveness. CONCLUSION: In summary, (1) this study confirmed our
      working hypothesis: Lower levels of hippocampal glutamatergic receptor densities
      correspond to lower sensorimotor gating in CPB-K mice, and (2) acute or
      subchronic treatment with CLZ did not elevate low PPI levels in CPB-K mice. Thus,
      further experiments will concentrate on other antipsychotic drugs to prove the
      predictive validity of this animal model.

PMID- 17541560
TI  - Multiwell fluorometric and colorimetric microassays for the evaluation of beta
      secretase (BACE-1) inhibitors.
AB  - The amyloid beta (Abeta) peptide is responsible for toxic amyloid plaque
      formation and is central to the aetiology of Alzheimer's disease (AD). It is
      generated by proteolytic processing of the amyloid precursor protein (APP) by
      beta-secretase (BACE-1) and gamma-secretase. Consequently, inhibition of BACE-1,
      a rate-limiting enzyme in the production of Abeta, is an attractive therapeutic
      approach to the treatment of Alzheimer's disease. This paper reports on improved
      microtiter plate-based fluorescence and colorimetric assays for the high
      throughput screening (HTS) of BACE-1 inhibitors achieved by employing, for the
      first time, casein fluorescein isothiocyanate (casein-FITC) and N-alpha-benzoyl
      D,L-arginine p-nitroanilide (BAPNA) as substrates, since they are known to be
      readily available and convenient substrates for proteases. The methods are based
      on the fluorescence enhancement following casein-FITC proteolysis and the visible
      absorbance of the p-nitroaniline (pNA) produced by BAPNA hydrolysis, with both
      reactions catalysed by BACE-1. Casein-FITC is a high-affinity substrate (K (m) =
      110 nM) for BACE-1, more so than the Swedish (SW) type peptide (a peptide
      containing the Swedish mutant of APP, a familiar mutation that enhances Abeta
      production). BACE-1 catalysis of casein-FITC proteolysis exhibited Michaelis
      Menten kinetic. Therefore, it was found that BACE-1 was saturable with casein
      FITC that was processed in a time- and pH-dependent manner with greater catalytic
      efficiency than observed for the SW peptide. The enantioselective hydrolysis of L
      BAPNA by BACE-1 was observed. L-BAPNA was hydrolysed ten times more efficiently
      by BACE-1 than the WT (wild-type peptide). The novel methods were validated using
      a FRET assay as an independent reference method. Therefore, in order to select
      new leads endowed with multifunctional activities, drugs for Alzheimer's disease
      (AD) - potent acetylcholinesterase (AChE) inhibitors - were tested for BACE-1
      inhibition using the proposed validated assays. Among these, donepezil, besides
      being an acetylcholinesterase inhibitor, was also found to be a BACE-1 inhibitor
      that displayed submicromolar potency (170 nM).

PMID- 17541561
TI  - Factorial-design optimization of gas chromatographic analysis of tetrabrominated
      to decabrominated diphenyl ethers. Application to domestic dust.
AB  - Gas chromatographic analysis of polybrominated diphenyl ethers (PBDEs) has been
      evaluated in an attempt to achieve better control of the separation process,
      especially for highly substituted congeners. Use of a narrow-bore capillary
      column enabled adequate determination of tetra, penta, hexa, hepta, octa, nona
      and decaBDE congeners in only one chromatographic run while maintaining
      resolution power similar to that of conventional columns. A micro electron
      capture detector (GC-microECD) was used. Chromatographic conditions were
      optimized by multifactorial experimental design, with the objective of obtaining
      not only high sensitivity but also good precision. In this way two different
      approaches to maximizing response and minimizing variability were tested, and are
      fully discussed. These optimum chromatographic conditions were then used to
      determine PBDEs extracted from domestic dust samples by microwave-assisted
      solvent extraction (MASE). Quantitative recovery (90-108%) was achieved for all
      the PBDEs and method precision (RSD < 13%) was satisfactory. Accuracy was tested
      by use of the standard reference material SRM 2585, and sub-ng g(-1) limits of
      detection were obtained for all compounds except BDE-209 (1.44 ng g(-1)).
      Finally, several samples of house dust were analysed by use of the proposed
      method and all the target PBDEs were detected in all the samples. BDE-209 was the
      predominant congener. Amounts varied from 58 to 1615 ng g(-1) and the average
      contribution to the total PBDE burden of 52%. The main congeners of the octaBDE
      mixture (BDE-183, BDE-197, BDE-207 and BDE-196) also made an important
      contribution (29%) to the total. These are the first data about the presence of
      these compounds in European house-dust samples. Finally, the sum of the main
      congeners in the pentaBDE commercial mixture (BDE-47, BDE-99, and BDE-100)
      contributed 14% to the total. Figure Polybrominated diphenyl ethers in House
      Dust.

PMID- 17541562
TI  - Determination of two phototransformation products of bentazone using quadrupole
      time-of-flight mass spectrometry.
AB  - The transformation products 2-(isopropylcarbamoyl)phenylsulfamic acid and 2-(1
      hydroxypropane-2-yl)-1,2-dihydroindazol-3-one could be determined during the
      photolysis of the herbicide bentazone. Degradation experiments were carried out
      with different types of water in a natural sunlight simulating system. Besides
      the anticipated hydroxylated bentazone, the second transformation product was
      identified by means of exact mass measurement using ultra-performance liquid
      chromatography/quadrupole time-of-flight mass spectrometry (UPLC/QqToF MS). Both
      phototransformation products occurred in all water types tested. The required
      irradiation time was matrix dependent. 2-(Isopropylcarbamoyl)phenylsulfamic acid
      was detected in a drainage channel in the Ebro river delta (Catalonia, Spain).

PMID- 17541563
TI  - Methods of sample preparation for determination of pesticide residues in food
      matrices by chromatography-mass spectrometry-based techniques: a review.
AB  - Much progress has been made in pesticide analysis over the past decade, during
      which time hyphenated techniques involving highly efficient separation and
      sensitive detection have become the techniques of choice. Among these, methods
      based on chromatographic separation with mass spectrometric detection have
      resulted in greater likelihood of identification and are acknowledged to be
      extremely useful and authoritative methods for determination of pesticide
      residues. Even with such powerful instrumental techniques, however, the risk of
      interference increases with the complexity of the matrix studied, so sample
      preparation before instrumental analysis is still mandatory in many applications,
      for example food analysis. This article summarizes the analytical characteristics
      of the different methods of sample-preparation for determination of pesticide
      residues in a variety of food matrices, and surveys their recent applications in
      combination with chromatographic mass spectrometric analysis. We discuss the
      advantages and the disadvantages of the different methods, address instrumental
      aspects, and summarize conclusions and perspectives for the future.

PMID- 17541564
TI  - A laser desorption ionization time-of-flight mass spectrometry investigation into
      triacylglycerols oxidation during thermal stressing of edible oils.
AB  - Laser desorption ionization time-of-flight mass spectrometry (LDI-TOF MS) was
      used to characterize olive and sunflower oils before and after thermally assisted
      oxidation in order to develop a rapid fingerprinting method for oil that contains
      unchanged and oxidized components. No matrix was used to assist laser desorption,
      and simplified mass spectra were obtained in the mass range of interest (m/z 500
      1000), where triacyl- and diacylglycerol ions were observed. Sample preparation
      was reduced to dissolving oil in chloroform saturated with NaCl. Sodiated
      triacylglycerols (TAGs), their epoxy/hydroxy and hydroperoxy derivatives, as well
      as TAGs with shortened chain fatty acids (beta-scission products) were clearly
      observed in the spectra. LDI-TOF MS rapidly provides semiquantitative information
      about the oxidation level of edible oil, and thus represents a very useful
      quality control tool.

PMID- 17541565
TI  - The NIH analytical methods and reference materials program for dietary
      supplements.
AB  - Quality of botanical products is a great uncertainty that consumers, clinicians,
      regulators, and researchers face. Definitions of quality abound, and include
      specifications for sanitation, adventitious agents (pesticides, metals, weeds),
      and content of natural chemicals. Because dietary supplements (DS) are often
      complex mixtures, they pose analytical challenges and method validation may be
      difficult. In response to product quality concerns and the need for validated and
      publicly available methods for DS analysis, the US Congress directed the Office
      of Dietary Supplements (ODS) at the National Institutes of Health (NIH) to
      accelerate an ongoing methods validation process, and the Dietary Supplements
      Methods and Reference Materials Program was created. The program was constructed
      from stakeholder input and incorporates several federal procurement and granting
      mechanisms in a coordinated and interlocking framework. The framework facilitates
      validation of analytical methods, analytical standards, and reference materials.

PMID- 17541566
TI  - Focus on sample handling.

PMID- 17541567
TI  - Combined use of total metal content and size fractionation of metal biomolecules
      to determine the provenance of pine nuts (Pinus pinea).
AB  - Four essential elements (Mn, Ni, Zn, and Cu) and their molecular-size
      distribution patterns have been determined, for twenty four samples of pine nuts
      from eight areas in Spain and Portugal (Huelva, Cadiz, Badajoz, Cataluna,
      Castilla, Madrid, Faro, and Coimbra), by size-exclusion liquid chromatography
      (SEC) coupled on-line to UV and inductively coupled plasma mass spectrometric
      (ICP-MS) detection. The variability observed in total element content and the
      size-exclusion profiles of elements in samples from distant areas were considered
      as chemical descriptors for characterization of geographic origin. A pattern
      recognition technique, the display method principal component analysis, was used
      as visualization technique to determine the provenance of the pine nuts
      collected. The results obtained confirmed that size fractionation profiles give
      more information for assessing the provenance of pine nuts than the total
      elements composition traditionally used for this purpose. Combination of these
      chemical descriptors was the most suitable choice for the samples studied. Figure
      This paper shows the application of an analytical approach based on total
      elements concentrations and the relative abundance of metal-biomolecules,
      estimated by the size-exclusion fractions, as chemical descriptors to determine
      the provenance of pine nuts. Principal component analysis (PCA) has been used as
      a visualization technique.

PMID- 17541568
TI  - Analysis of mismatched DNA by mismatch binding ligand (MBL)-Sepharose affinity
      chromatography.
AB  - Mismatch binding molecules (MBLs), strongly and selectively bound to the
      mismatched base pair in duplex DNA, were immobilized on Sepharose. Three MBL
      Sepharose columns were prepared with three MBLs, naphthyridine dimer (ND),
      naphthyridine-azaquinolone (NA), and aminonaphthyridine dimer (amND), which
      exhibited different binding profiles to the mismatched base pairs. These three
      MBL-Sepharose columns showed characteristic elution profiles for DNA duplexes
      containing mismatched base pairs. The ND-Sepharose column separated the G-G and G
      A mismatched DNA from fully matched duplexes. The NA-Sepharose column separated
      the A-A and G-A mismatched DNA from other DNA duplexes. The amND-Sepharose column
      separated the C-C mismatched DNA. These chromatographic profiles were very
      consistent with the binding preference of each MBL. By changing the elution
      conditions from sodium hydroxide to sodium chloride, MBL-Sepharose columns were
      also able to separate the mismatched DNA that weakly bound to the MBL from fully
      matched DNA duplex. Figure MBL-Sepharose affinity chromatography successfully
      separates the mismatched duplex DNA from fully matched duplex.

PMID- 17541569
TI  - Solution to the chemical uncertainty principle challenge.

PMID- 17541570
TI  - Measuring human-error probabilities in drug preparation: a pilot simulation
      study.
AB  - OBJECTIVES: Designing a safe medication process requires the ability to model its
      reliability using methods such as probabilistic risk assessment (PRA). However,
      lack of data, especially on human-error probabilities (HEPs), limits its use. To
      assess whether small-scale simulations could help generate HEP data, a pilot
      study was conducted among nurses and anaesthetists. It focused on two core
      activities, namely, the manual preparation of medications and the arithmetic
      necessary to prepare drugs. Its specific objectives were to evaluate whether HEPs
      could be high enough to be measurable and to determine whether these HEPs could
      be sensitive to individuals and task details. These would give some insight into
      the level of detail required by PRA analysis. METHODS: Thirty nurse and 28
      anaesthetist volunteers were involved in the experiment. Nurses and anaesthetists
      had to prepare medications for 20 patients and 22 syringes of various drugs,
      respectively. Both groups had to perform 22 calculations relating to the
      preparation of drugs. HEPs, distribution of HEPs and dependency of HEPs on
      individuals and task details were assessed. RESULTS: In the preparation tasks,
      overall HEP was 3.0% for nurses and 6.5% for anaesthetists. In the arithmetic
      tasks, overall HEP was 23.8% for nurses and 8.9% for anaesthetists. A
      statistically significant difference was noted between the two groups. In both
      preparation and arithmetic tasks, HEPs were dependent on individual nurses but
      not on individual anaesthetists. In every instance, HEPs were dependent on task
      details. CONCLUSION: Our study illustrates that small-scale simulations represent
      an interesting way of generating HEPs. HEPs are, indeed, in the range of 10(-2)
      and 10(-1). But in most cases, HEPs depend heavily on operators and task details.
      This dependency means that the influence of these parameters must be determined
      before advanced PRA analysis. There is therefore an urgent need to develop
      experimental research into assessing this influence by means of randomised
      controlled trials.

PMID- 17541571
TI  - Pharmacokinetics of morphine-6-glucuronide following oral administration in
      healthy volunteers.
AB  - AIM: After oral administration, morphine-6-glucuronide (M6G) displays an atypical
      absorption profile with two peak plasma concentrations. A proposed explanation is
      that M6G is hydrolysed to morphine in the colon, which is then absorbed and
      subsequently undergoes metabolism in the liver to morphine-3-glucuronide (M3G)
      and M6G. The aims of this study were to confirm and elucidate the biphasic
      absorption profile as well as clarify the conversion of M6G to morphine after a
      single oral administration of M6G in healthy volunteers. METHODS: The study was
      conducted accordingly to a nonblinded, randomised, balanced three-way crossover
      design in eight healthy male subjects. The subjects received 200 mg oral M6G, 50
      mg oral M6G and 30 mg oral morphine. Blood samples were collected until 72 h
      after M6G administration and until 9 h after morphine administration. Paracetamol
      and sulfasalazine were coadministered with M6G as markers for the gut contents
      reaching the duodenum and colon, respectively. RESULTS: The plasma concentration
      peaks of M6G were seen at 4.0 (2.0-6.0) and 18 (12.0-24.0) h after 200 mg M6G and
      at 3.5 (2.0-6.0) and 21.3 (10.0-23.3) h after 50 mg M6G, which was in agreement
      with previously published results. The K(M6G_abs)/K(M6G_M6G) ratio was found to
      be 10. CONCLUSION: The pharmacokinetic profile of M6G after oral administration
      was confirmed and with the presence of M3G and morphine in plasma after oral
      administration of M6G, proof seems to be found of the constant and prolonged
      absorption of M6G. The K(M6G_abs)/K(M6G_M6G) ratio of 10 indicates that the
      second absorption peak of M6G consists of approximately 10 times more absorbed
      M6G than reglucuronidated M6G. However, further studies are required to determine
      the precise kinetics of the second absorption peak.

PMID- 17541572
TI  - Urinary 8-hydroxydeoxyguanosine is elevated in patients with nephrolithiasis.
AB  - 8-hydroxydeoxyguanosine (8-OHdG) is an oxidatively modified guanosine, which has
      been widely used as an oxidative DNA damage marker in various diseases. The
      present study aimed to determine urinary 8-OHdG in nephrolithiasis patients and
      evaluate its clinical significance. Thirty-six nephrolithiasis patients and 30
      healthy subjects were recruited. Urine volume, creatinine, malondialdehyde, beta
      N-acetylglucosaminidase (NAG) activity and proteins were measured in 24 h urine
      samples. Urinary 8-OHdG was determined by competitive enzyme-linked immunosorbent
      assay. Mineral composition of stones was analyzed using Fourier-transformed
      infrared spectroscopy. Nephrolithiasis patients excreted urinary 8-OHdG
      significantly higher than healthy controls. Urinary 8-OHdG levels compared among
      patients with calcium oxalate, struvite and uric acid stones were insignificantly
      different. The urinary NAG activity correlated positively with urinary 8-OHdG.
      Multiple linear regression showed that urinary NAG activity was an independent
      predictor of urinary 8-OHdG level. Receiver operating characteristic analysis
      revealed that the urinary 8-OHdG test was adequate for diagnosing
      nephrolithiasis. At 10 mug/g creatinine cutoff, the 8-OHdG test imparted high
      specificity (96.67%) and a positive predictive value (91.67%). In conclusion,
      this is the first report of elevated urinary 8-OHdG excretion in nephrolithiasis
      patients indicating increased oxidative DNA damage. Increased renal tubular
      damage was independently associated with elevated urinary 8-OHdG. Elevated
      urinary 8-OHdG levels adjunct with metabolic profile may be useful for
      identifying people at risk of stone development.

PMID- 17541573
TI  - Perforation of the upper ureter: a rare complication of extracorporeal shock wave
      lithotripsy.
AB  - Perforation of the upper ureter is a rare but serious complication of
      extracorporeal shock wave lithotripsy (SWL). Ureteral perforation can cause a
      series of problems including the retroperitoneal urinoma, urosepsis, abscess
      formation, infection, and subsequent renal function impairment. We reported here
      a rare case of SWL-induced upper ureteral rupture resulting in an expanding
      retroperitoneal urinoma that required percutaneous drainage. Ureteral perforation
      was treated successfully without major surgical intervention by employing
      temporary percutaneous drainage and antibiotics. The present case indicates that
      potential ureter rupture may form in rare cases; especially in patients having
      infected stones and exposed to a high number of shock waves. This complication
      further emphasizes the importance of adequate pre-and post-operative evaluation
      and the precise identification of the cause of the persistent pain after SWL.

PMID- 17541574
TI  - Coronary magnetic resonance angiography and vessel wall imaging in children with
      Kawasaki disease.
AB  - BACKGROUND: In patients with Kawasaki disease (KD) serial evaluation of the
      distribution and size of coronary artery aneurysms (CAA) is necessary for risk
      stratification and therapeutic management. OBJECTIVE: To apply whole-heart
      coronary MR angiography (CMRA) and black-blood coronary vessel wall imaging in
      children with KD. MATERIALS AND METHODS: Six children (mean age 4.6 years, range
      2.5-7.8 years) with KD underwent CMRA using a free-breathing, T2-prepared, three
      dimensional steady-state free-precession (3D-SSFP), whole-heart approach with
      navigator gating and tracking. Vessel walls were imaged with an ECG-triggered and
      navigator-gated double inversion recovery (DIR) black-blood segmented turbo spin
      echo sequence. RESULTS: There was complete agreement between CMRA and
      conventional angiography (n=6) in the detection of CAA (n=15). Excellent
      agreement was found between the two techniques in determining the maximal
      diameter (mean difference 0.2+/-0.7 mm), length (mean difference 0.1+/-0.8 mm)
      and distance from the ostium (mean difference -0.8+/-2.1 mm) of the CAAs. In all
      subjects with a CAA, abnormally thickened vessel walls were found (2.5+/-0.5 mm).
      CONCLUSIONS: CMRA accurately defines CAA in free-breathing sedated children with
      KD using the whole-heart approach and detects abnormally thickened vessel walls.
      This technique may reduce the need for serial X-ray coronary angiography, and
      improve risk stratification and monitoring of therapy.

PMID- 17541575
TI  - Imaging features of gastrointestinal tract duplications in infants and children:
      from oesophagus to rectum.
AB  - Gastrointestinal tract duplications are uncommon congenital abnormalities arising
      anywhere along the alimentary tract. The most common modalities used to image
      duplications are US and contrast medium examinations. CT and MRI are less often
      used, but can be helpful in difficult cases that require a multiplanar approach.
      In this article, we discuss and illustrate a wide spectrum of gastrointestinal
      tract duplications from the oesophagus to the rectum, and illustrate the
      associated abnormalities of gastrointestinal tract duplications.

PMID- 17541576
TI  - Magnetic resonance in the solid state: applications to protein folding, amyloid
      fibrils and membrane proteins.
AB  - Solid-state nuclear magnetic resonance (ssNMR) represents a spectroscopic method
      to study non-crystalline molecules at atomic resolution. Advancements in
      spectroscopy and biochemistry provide increasing possibilities to study structure
      and dynamics of complex biomolecular systems by ssNMR. Here, methodological
      aspects and applications in the context of protein folding and aggregation are
      discussed. In addition, studies involving membrane proteins are considered.

PMID- 17541577
TI  - Distributions of single nucleotide polymorphisms in differential chromosome
      segments of congenic resistant strains that define minor histocompatibility
      antigens.
AB  - Minor histocompatibility antigens (MiHAs) stimulate the rejection of allografts
      when donors and recipients are matched at the major histocompatibility complex
      (MHC). The majority of identified autosomal MiHAs were generated by non
      synonymous (NS) substitutions that alter MHC class I-binding peptides. The mosaic
      distribution of single nucleotide polymorphisms (SNPs) that distinguish inbred
      mouse strains led us to hypothesize that MiHA genes defined by congenic strains
      on C57BL/6 and C57BL/10 backgrounds map to chromosomal regions with relatively
      high numbers of NS SNPs that distinguish C57 strains from other common inbred
      strains. To test this hypothesis, we mapped the ends of differential chromosome
      segments of congenic strains, which define 12 MiHAs, relative to microsatellites
      and SNPs. The lengths of differential segments ranged from 9.7 to 105.9 Mbp in
      congenic strains where no attempts were made to select recombinants within these
      segments. There was no apparent correlation between differential segment length
      and number of backcrosses, suggesting that factors other than the number of
      opportunities for recombination affected the differential segment lengths in
      these congenics. These differential segments included higher numbers of NS SNPs
      that distinguish C57BL/6J from A/J, DBA/2J, and 129S1/J than would be predicted
      if these SNPs were uniformly distributed along the chromosomes. The most extreme
      case was the H8 congenic that included 74% of the SNPs on chromosome 14 within
      its 9.7-11.1 Mbp differential segment. These results point toward a direct
      relationship between the level of genomic divergence, as indicated by numbers of
      NS SNPs, and numbers of MiHAs that collectively determine the magnitude of
      allograft rejection.

PMID- 17541578
TI  - Evolution of CC chemokines in teleost fish: a case study in gene duplication and
      implications for immune diversity.
AB  - Chemokines are a superfamily of cytokines responsible for regulating cell
      migration under both inflammatory and physiological conditions. CC chemokines are
      the largest subfamily of chemokines, with 28 members in humans. A subject of
      intense study in mammalian species, the known functional roles of CC chemokines
      ligands in both developmental and disease conditions continue to expand. They are
      also an important family for the study of gene copy number variation and tandem
      duplication in mammalian species. However, little is known regarding the
      evolutionary origin and status of these ligands in primitive vertebrates such as
      teleost fish. In this paper, we review the evolution of the teleost fish CC
      chemokine gene family, noting evidence of widespread tandem gene duplications and
      examining the implications of this phenomenon on immune diversity. Through
      extensive phylogenetic analysis of the CC chemokine sets of four teleost species,
      zebrafish, catfish, rainbow trout, and Atlantic salmon, we identified seven large
      groups of CC chemokines. It appeared that several major groups of CC chemokines
      are highly related including the CCL19/21/25 group, the CCL20 group, CCL27/28
      group, and the fish-specific group. In the three remaining groups that contained
      the largest number of members, the CCL17/22 group, the MIP group, and the MCP
      group, similarities among species members were obscured by rapid, tandem
      duplications that may contribute to immune diversity.

PMID- 17541579
TI  - Development of an efficient method for screening microorganisms by using
      symbiotic association between Nasutitermes takasagoensis and intestinal
      microorganisms.
AB  - Screening method of microorganisms that utilized the symbiotic association
      between insect (Nasutitermes takasagoensis: Nt) and intestinal microorganisms was
      developed. The existence of desired microorganisms that grew by degrading
      difficult-to-degrade materials in the gut was detected using survivability of Nt
      as an indicator. The desired microorganisms were isolated from the survived Nt.
      It was thought that guts of Nt behave as continuous culture systems whereby
      microorganisms that cannot degrade diet components are washed out, whereas those
      that can degrade it are retained and concentrated in the gut. About 60% of Nt fed
      with phenol artificial diet (PAD) died within 7 days, while 4% of termites
      survived for 9 days. The structure of intestinal microorganisms of the survived
      Nt fed with PAD differed from the bacterial communities obtained from enrichment
      culture (which contained phenol) of wood-feeding Nt. Relatively high colonies
      (650-times) were detected in the gut of Nt fed on phenol artificial diet compared
      with those obtained when Nt was fed on wood. Seven denaturing gradient gel
      electrophoresis (DGGE) bands were detected from gut of wood-feeding Nt, whereas
      11 DGGE-bands were detected from that of phenol-feeding Nt. Out of 11 DGGE-bands,
      5 of them were sequenced, and bacterial species including phenol-degrading
      bacteria were identified.

PMID- 17541580
TI  - Acid phosphatase production by recombinant Arxula adeninivorans.
AB  - Acid phosphatase production by recombinant Arxula adeninivorans was carried out
      in submerged fermentation. Using the Plackett-Burman design, three fermentation
      variables (pH, sucrose concentration, and peptone concentration) were identified
      to significantly affect acid phosphatase and biomass production, and these were
      optimized using response surface methodology of central composite design. The
      highest enzyme yields were attained in the medium with 3.9% sucrose and 1.6%
      peptone at pH 3.8. Because of optimization, 3.86- and 4.19-fold enhancement in
      enzyme production was achieved in shake flasks (17,054 U g(-1) DYB) and
      laboratory fermenter (18,465 U g(-1) DYB), respectively.

PMID- 17541581
TI  - Bioremediation and monitoring of aromatic-polluted habitats.
AB  - Bioremediation may restore contaminated soils through the broad biodegradative
      capabilities evolved by microorganisms towards undesirable organic compounds.
      Understanding bioremediation and its effectiveness is rapidly advancing, bringing
      available molecular approaches for examining the presence and expression of the
      key genes involved in microbial processes. These methods are continuously
      improving and require further development and validation of primer- and probe
      based analyses and expansion of databases for alternative microbial markers.
      Phylogenetic marker approaches provide tools to determine which organisms are
      present or generally active in a community; functional gene markers provide only
      information concerning the distribution or transcript levels (deoxyribonucleic
      acid [DNA]- or messenger ribonucleic acid [mRNA]-based approaches) of specific
      gene populations across environmental gradients. Stable isotope probing methods
      offer great potential to identify microorganisms that metabolize and assimilate
      specific substrates in environmental samples, incorporating usually a rare
      isotope (i.e., (13)C) into their DNA and RNA. DNA and RNA in situ
      characterization allows the determination of the species actually involved in the
      processes being measured. DNA microarrays may analyze the expression of thousands
      of genes in a soil simultaneously. A global analysis of which genes are being
      expressed under various conditions in contaminated soils will reveal the
      metabolic status of microorganisms and indicate environmental modifications
      accelerating bioremediation.

PMID- 17541582
TI  - Cloning and characterization of three epoxide hydrolases from a marine bacterium,
      Erythrobacter litoralis HTCC2594.
AB  - Previously, we reported that ten strains belonging to Erythrobacter showed
      epoxide hydrolase (EHase) activities toward various epoxide substrates. Three
      genes encoding putative EHases were identified by analyzing open reading frames
      of Erythrobacter litoralis HTCC2594. Despite low similarities to reported EHases,
      the phylogenetic analysis of the three genes showed that eeh1 was similar to
      microsomal EHase, while eeh2 and eeh3 could be grouped with soluble EHases. The
      three EHase genes were cloned, and the recombinant proteins (rEEH1, rEEH2, and
      rEEH3) were purified. The functionality of purified proteins was proved by
      hydrolytic activities toward styrene oxide. EEH1 preferentially hydrolyzed (R)
      styrene oxide, whereas EEH3 preferred to hydrolyze (S)-styrene oxide,
      representing enantioselective hydrolysis of styrene oxide. On the other hand,
      EEH2 could hydrolyze (R)- and (S)-styrene oxide at an equal rate. The optimal pH
      and temperature for the EHases occurred largely at neutral pHs and 40-55 degrees
      C. The substrate selectivity of rEEH1, rEEH2, and rEEH3 toward various epoxide
      substrates were also investigated. This is the first representation that a strict
      marine microorganism possessed three EHases with different enantioselectivity
      toward styrene oxide.

PMID- 17541583
TI  - Functional imaging of multidrug resistance in an orthotopic model of osteosarcoma
      using 99mTc-sestamibi.
AB  - PURPOSE: The purpose of this work was the development of an orthotopic model of
      osteosarcoma based on luciferase-expressing tumour cells for the in vivo imaging
      of multidrug resistance (MDR) with (99m)Tc-sestamibi. METHODS: Doxorubicin
      sensitive (143B-luc(+)) and resistant (MNNG/HOS-luc(+)) osteosarcoma cell lines
      expressing different levels of P-glycoprotein and carrying a luciferase reporter
      gene were inoculated into the tibia of nude mice. Local tumour growth was
      monitored weekly by bioluminescence imaging and X-ray. After tumour growth, a
      (99m)Tc-sestamibi dynamic study was performed. A subset of animals was pre
      treated with an MDR inhibitor (PSC833). Images were analysed for calculation of
      (99m)Tc-sestamibi washout half-life (t (1/2)), percentage washout rate (%WR) and
      tumour/non-tumour (T/NT) ratio. RESULTS: A progressively increasing
      bioluminescent signal was detected in the proximal tibia after 2 weeks. The t
      (1/2) of (99m)Tc-sestamibi was significantly shorter (p < 0.05) in drug-resistant
      MNNG/HOS-luc(+) tumours (t (1/2) = 87.3 +/- 15.7 min) than in drug-sensitive 143B
      luc(+) tumours (t (1/2) = 161.0 +/- 47.4 min) and decreased significantly with
      PSC833 (t (1/2) = 173.0 +/- 24.5 min, p < 0.05). No significant effects of PSC833
      were observed in 143B-luc(+) tumours. The T/NT ratio was significantly lower (p <
      0.05) in MNNG/HOS-luc(+) tumours than in 143B-luc(+) tumours at early (1.55 +/-
      0.22 vs 2.14 +/- 0.36) and delayed times (1.12 +/- 0.11 vs 1.62 +/- 0.33). PSC833
      had no significant effects on the T/NT ratios of either tumour. CONCLUSION: The
      orthotopic injection of tumour cells provides an animal model suitable for
      functional imaging of MDR. In vivo bioluminescence imaging allows the non
      invasive monitoring of tumour growth. The kinetic analysis of (99m)Tc-sestamibi
      washout provides information on the functional activity of MDR related to P
      glycoprotein expression and its pharmacological inhibition in osteosarcoma.

PMID- 17541584
TI  - Prognostic and diagnostic accuracy of [18F]FDG-PET/CT in 190 patients with
      carcinoma of unknown primary.
AB  - PURPOSE: The aim of the study was to determine the accuracy of
      [(18)F]fluorodeoxyglucose (FDG) PET/CT in the search for the primary and the
      presence of a malignancy. The prognostic value of FDG-PET/CT information was
      tested. METHODS: A total of 190 patients were retrospectively analysed: 82 with
      histologically proven metastases (HPM) and 108 with clinical suspicion of the
      presence of a malignancy (CSM). The sensitivity and specificity were determined.
      Overall survival was calculated to evaluate the prognostic value of the FDG
      PET/CT findings. RESULTS: In the search for the primary, the sensitivity and
      specificity were 62.0% and 81.9%, respectively. In the search for the presence of
      a malignancy, the sensitivity and specificity were 93.6% and 85.7%, respectively.
      Between the HPM and CSM groups, no significant difference in sensitivity and
      specificity was found either in the search for the primary or in the search for
      the presence of a malignancy. No significant difference in the sensitivity and
      specificity was found between 78 patients who were investigated by contrast
      enhanced FDG-PET/CT and the remaining patients. A significantly shorter overall
      survival was found among patients with positive FDG-PET/CT findings compared with
      patients with negative findings (p = 0.00001); no significant difference in
      survival was found between the HPM and the CSM group (p = 0.770). CONCLUSION: FDG
      PET/CT imaging is very helpful in the search for the presence of a malignancy in
      patients with carcinoma of unknown primary syndrome. FDG-PET/CT is less accurate
      in identifying exactly the site of a primary. Discovery of a hypermetabolic
      lesion was associated with the worst survival rate.

PMID- 17541585
TI  - Early assessment of therapy response in malignant lymphoma with the thymidine
      analogue [18F]FLT.
AB  - PURPOSE: The aim of this study was to determine whether the thymidine analogue 3'
      deoxy-3'-[(18)F]fluorothymidine ([(18)F]FLT) is adequate for early evaluation of
      the response of malignant lymphoma to antiproliferative treatment in a mouse
      xenotransplant model. METHODS: Immunodeficient mice bearing a follicular lymphoma
      xenotransplant were treated with high-dose chemotherapy (cyclophosphamide, n =
      10), immunotherapy (CD20 mAb, ibritumomab-tiuxetan, n = 10) or radioimmunotherapy
      ([(90)Y]CD20 mAb, Zevalin, n = 10). Forty-eight hours after treatment,
      antiproliferative effects were assessed with [(18)F]FLT. Ninety minutes after
      i.v. injection of 5-10 MBq [(18)F]FLT, mice were sacrificed and radioactivity
      within the tumour and normal organs was measured using a gamma counter and
      calculated as % ID/g. The proliferation fraction in tissue samples derived from
      treated and untreated tumours was evaluated by Ki-67 immunohistochemistry, which
      served as the reference for proliferative activity. RESULTS: In untreated
      lymphoma, the mean proliferation fraction was 83.6%. After chemotherapy, the mean
      proliferation fraction decreased to 39.3% (p = 0.0001), after immunotherapy to
      77.6% (p = 0.0078) and after radioimmunotherapy to 78.8% (p = 0.014). In none of
      the animals was a significant change in tumour size observed. In untreated
      lymphoma, tumoural [(18)F]FLT uptake was 5.4% ID/g, after chemotherapy it was
      1.5% (p = 0.0005), after immunotherapy, 3.9% (non-significant), and after
      radioimmunotherapy, 5.8% (non-significant). CONCLUSION: In a lymphoma
      xenotransplant model, [(18)F]FLT detects early antiproliferative drug activity
      before changes in tumour size are visible. These findings further support the use
      of [(18)F]FLT-PET for imaging early response to treatment in malignant lymphoma.

PMID- 17541586
TI  - PET imaging of acute and chronic inflammation in living mice.
AB  - PURPOSE: In this study, we evaluated the 12-O-tetradecanoyl-phorbol-13-acetate
      (TPA)-induced acute and chronic inflammation in living mice by PET imaging of TNF
      alpha and integrin alpha(v)beta(3) expression. METHODS: TPA was topically applied
      to the right ear of BALB/c mice every other day to create the inflammation model.
      (64)Cu-DOTA-etanercept and (64)Cu-DOTA-E{E[c(RGDyK)](2)}(2) were used for PET
      imaging of TNF-alpha and integrin alpha(v)beta(3) expression in both acute and
      chronic inflammation. Hematoxylin and eosin staining, ex vivo autoradiography,
      direct tissue sampling, and immunofluorescence staining were also performed to
      confirm the non-invasive PET imaging results. RESULTS: The ear thickness
      increased significantly and the TNF-alpha level more than tripled after a single
      TPA challenge. MicroPET imaging using (64)Cu-DOTA-etanercept revealed high
      activity accumulation in the inflamed ear, reaching 11.1 +/- 1.3, 13.0 +/- 2.0,
      10.9 +/- 1.4, 10.2 +/- 2.2%ID/g at 1, 4, 16, and 24 h post injection,
      respectively (n = 3). Repeated TPA challenges caused TPA-specific chronic
      inflammation and reduced (64)Cu-DOTA-etanercept uptake due to lowered TNF-alpha
      expression. (64)Cu-DOTA-E{E[c(RGDyK)](2)}(2) uptake in the chronically inflamed
      ears (after four and eight TPA challenges) was significantly higher than in the
      control ears and those after one TPA challenge. Immunofluorescence staining
      revealed increased integrin beta(3) expression, consistent with the non-invasive
      PET imaging results using (64)Cu-DOTA-E{E[c(RGDyK)](2)}(2) as an integrin
      alpha(v)beta(3)-specific radiotracer. Biodistribution and autoradiography studies
      further confirmed the quantification capability of microPET imaging. CONCLUSION:
      Successful PET imaging of TNF-alpha expression in acute inflammation and integrin
      alpha(v)beta(3) expression in chronic inflammation provides the rationale for
      multiple target evaluation over time to fully understand the inflammation
      processes.

PMID- 17541587
TI  - Rituximab in autoimmune pancytopenia: a case report and review of literature.

PMID- 17541588
TI  - Stable low IgG levels in relapsed non-Hodgkin's lymphomas.

PMID- 17541589
TI  - A phase II trial of transcatheter arterial infusion chemotherapy with an
      epirubicin-Lipiodol emulsion for advanced hepatocellular carcinoma refractory to
      transcatheter arterial embolization.
AB  - INTRODUCTION: Transcatheter arterial embolization (TAE) has been recognized as an
      effective palliative treatment option for advanced hepatocellular carcinoma
      (HCC). However, no effective alternative treatments for TAE-refractory HCC have
      yet been established. The aim of this study was to evaluate the antitumor
      activity and toxicity of transcatheter arterial infusion chemotherapy using an
      epirubicin-Lipiodol emulsion in patients with TAE-refractory HCC. METHODS:
      Patients with TAE-refractory HCC were enrolled. A dose of 60 mg/m(2) epirubicin
      emulsified in Lipiodol and contrast medium was administered from the feeding
      artery of the HCC. Treatment was repeated every 4 to 12 weeks if there was no
      evidence of tumor progression or unacceptable toxicity. RESULTS: Twenty patients
      were enrolled in this trial. The median number of treatment courses was 1 (range
      1-4). Among the enrolled patients, one (5%) achieved a partial response, and
      three (15%) showed a minor response. Five (25%) patients had no change and 11
      (55%) showed progressive disease. The median survival time, 1-year survival rate
      and median progression-free survival time for the patients as a whole were 12.4
      months, 52.6%, and 1.1 months, respectively. The main grade 3 and 4 toxicities
      were leukocytopenia (35%), neutropenia (65%), thrombocytopenia (30%), and
      elevations of the aspartate aminotransferase (45%) and alanine aminotransferase
      (35%) levels. These toxicities were generally brief and reversible. CONCLUSION:
      Transcatheter arterial infusion chemotherapy with an epirubicin-Lipiodol emulsion
      appears to have only modest activity with moderate toxicity for treatment of
      patients with TAE-refractory HCC. These findings do not support its use in
      practice, and further studies with the same regimen in patients with TAE
      refractory HCC are not recommended.

PMID- 17541590
TI  - Plasma and cerebrospinal fluid pharmacokinetics of valproic acid after oral
      administration in non-human primates.
AB  - PURPOSE: Valproic acid (VPA), a widely used antiepileptic, also inhibits histone
      deacetylase (HDAC), and is undergoing evaluation as an anti-cancer agent. We
      studied the pharmacokinetics of VPA in the plasma and cerebrospinal fluid (CSF)
      in a non-human primate model that is highly predictive of human CSF penetration
      to determine if levels of VPA required to inhibit HDAC in in vivo models can be
      attained. METHODS: Oral VPA, 75 mg/kg, was administered to four non-human
      primates. Serial samples of blood (n = 4) and CSF (n = 3) were obtained for
      pharmacokinetic studies of total and free VPA. Plasma and CSF VPA concentrations
      were measured using the commercially available Abbott AxSYM VPA assay reagent
      system (Abbott Laboratories, Abbott Park, IL, USA). The resultant plasma and CSF
      data were evaluated using pharmacokinetic modeling methods. RESULTS: At a dose of
      75 mg/kg, the maximum plasma concentration of VPA was 130.1 +/- 70.6 microg/ml
      (mean +/- standard deviation) for total drug and 53.3 +/- 44.4 microg/ml for free
      drug. The mean plasma area under the curve (AUC) for total drug was 680 +/- 233
      microg/ml h and for free drug 146 +/- 89 microg/ml hr. The maximum CSF
      concentration occurred 2-3 h after administration and was 28.2 +/- 18.6
      microg/ml. The CSF AUC for VPA was 108 +/- 52 microg/ml h. The CSF penetration of
      VPA was 12.9 +/- 5.1% for total drug and 57.0 +/- 8.7% for free drug.
      Disappearance from the plasma followed non-linear kinetics with a V (max) of
      321.2 +/- 65.6 microg/kg/min and a K (m) of 17.2 +/- 13.7 mg/l. CONCLUSION:
      Valproic acid deserves further study for the treatment of CNS tumors given its
      high CSF penetration after oral dosing coupled with the anti-tumor activity
      observed in preclinical studies.

PMID- 17541591
TI  - Evaluation of oral versus intravenous dose of vinorelbine to achieve equivalent
      blood exposures in patients with solid tumours.
AB  - Patient's preference is for oral chemotherapy when both oral and i.v. are
      available, provided that efficacy is equivalent. Reliable switch from oral to
      i.v. is possible if correspondence between respective doses has been established.
      Vinorelbine oral was developed as a line extension of VRL i.v. on the basis that
      similar AUCs result in similar activities. From a first crossover study on 24
      patients receiving VRL 25 mg/m2 i.v. and 80 mg/m2 oral data extrapolation
      concluded on AUCs bioequivalence between Vinorelbine 30 mg/m2 i.v. and 80 mg/m2
      oral. A new trial was performed to support this calculation. In a crossover
      design study on patients (PS 0-1) with advanced solid tumours (44% breast
      carcinoma), VRL was administered (30 mg/m2 i.v., 80 mg/m2 oral) with a standard
      meal and 5-HT3 antagonists, at 2 weeks interval. Pharmacokinetics was performed
      over 168 h and VRL was measured by LC-MS/MS. Statistics included bioequivalence
      tests. Forty-eight patients were evaluable for PK: median age 58 years (25-71),
      PS0/PS1: 20/28, M/F: 11/37. Mean AUCs were 1,230 +/- 290 and 1,216 +/- 521 ng/ml
      for i.v. and oral, respectively. The confidence interval of the AUC ratio (0.83
      1.03) was within the required regulatory range (0.8-1.25) and proved the
      bioequivalence between the two doses. The absolute bioavailability was 37.8 +/-
      16.0%, and close to the value from the first study (40%). Patient tolerability
      was globally comparable between both forms with no significant difference on
      either haematological or non-haematological toxicities (grade 3-4). This new
      study, conducted on a larger population, confirmed the reliable dose
      correspondence previously established between vinorelbine 80 mg/m2 oral and 30
      mg/m2 i.v.

PMID- 17541592
TI  - Preclinical antitumor activity of the oral platinum analog satraplatin.
AB  - PURPOSE: Satraplatin is an orally available platinum analog. The purpose of this
      study was to better characterize satraplatin's preclinical antitumor efficacy in
      a variety of sensitive and resistant human tumor cell lines and in a prostate
      cancer xenograft model and to evaluate the effect of satraplatin on PSA
      expression and/or secretion in a prostate cancer cell line. METHODS: Satraplatin
      and its primary metabolite JM-118 were preclinically tested for their cytotoxic
      activity in a range of cancer cells including: human prostate, those forming the
      NCI drug screening panel, and those resistant to anti-cancer drugs. Also, the
      antiproliferative efficacy of satraplatin was tested in vivo in a human prostate
      cancer model. The effect of satraplatin and JM-118 on PSA transcription was
      measured by quantitative real time PCR. RESULTS: Satraplatin and JM-118 inhibited
      in vitro and in vivo the growth of prostate cancer cells in a dose-dependent
      fashion. The IC50 cytotoxicity values for satraplatin ranged from 1 to 3 microM
      for androgen-insensitive cells and was 11 microM for the androgen-sensitive cell
      line. Interestingly, JM-118 was up to 16-fold more potent than satraplatin. Oral
      administration of satraplatin to nude mouse PC-3 xenograft models inhibited the
      growth of these human tumors. Satraplatin had no direct effect on PSA
      transcription and the observed decrease in secreted PSA correlated with a
      decrease in cell number. When evaluated in the NCI drug-screening panel,
      satraplatin was most active in leukemia and small cell lung cancer cell lines.
      Both satraplatin and JM-118 were tested on cells resistant to chemotherapeutic
      agents. Satraplatin and JM-118 were equally active in the cisplatin-resistant
      A129cp80 ovarian carcinoma cell line, with activity comparable to that observed
      in the parent line. Neither expression of MDR1, BCRP, MRP1, nor altered tubulin
      or topoisomerase I were found to mediate resistance to satraplatin or JM-118.
      Although these resistance mechanisms contribute to drug resistance for a number
      of chemotherapeutics, they do not appear to play a role in satraplatin
      resistance. CONCLUSIONS: These results demonstrate that satraplatin and JM-118
      have preclinical antitumor activity in human prostate cancer and other tumor
      types as well, including several cell lines displaying drug resistance to
      cisplatin, docetaxel and mitoxantrone. In addition, the results suggest that PSA
      should be further evaluated as a relevant marker of clinical response in patients
      with prostate cancer treated with satraplatin.

PMID- 17541593
TI  - Treatment parameters modulating regression of human melanoma xenografts by an
      antibody-drug conjugate (CR011-vcMMAE) targeting GPNMB.
AB  - PURPOSE: To investigate the pharmacological properties of the CR011-vcMMAE fully
      human antibody-drug conjugate (ADC), such as dose titrations, quantitation of the
      time (days) to complete regression, pharmacokinetics, and schedule dependency.
      Our prior study characterized a fully human antibody to GPNMB covalently linked
      to monomethylauristatin E, CR011-vcMMAE, and further demonstrated cell surface
      staining of melanoma lines susceptible to the immunoconjugate's cytotoxicity
      (Clin Cancer Res 2005; 12(4): 1373-1382). METHODS: The human SK-MEL-2 and SK-MEL
      5 melanoma xenografts were used in athymic mice to assess anti-tumor efficacy.
      After s.c. implantation, tumors became established (60-100 mg), and treatment
      commenced by i.v. injection of the immunoconjugate or vinblastine or paclitaxel.
      Short-term anti-tumor effects (inhibition of tumor growth) and long-term effects
      (complete regression) were observed. RESULTS: CR011-vcMMAE induced regression of
      established human SK-MEL-2 and SK-MEL-5 xenografts at doses from 1.25 to 80 mg/kg
      treatment when administered intravenously every 4 days (4 treatments);
      strikingly, regressions were not associated with re-growth during the observation
      period (200 days). The disappearance rate of implants was dose dependent (minimum
      time, 18.5 days). Detectable serum CR011-vcMMAE >or=1 microg/mL (approximately
      0.01 microM) was observed for >30 days post-dose; CR011-vcMMAE showed an
      elimination half-life of 10.3 days. A low volume of distribution suggested that
      CR011-vcMMAE was confined to blood and interstitial fluid. CR011-vcMMAE could be
      delivered by either a single bolus dose or by intermittent dosing (i.e., every 1,
      2, 4, 8, or 16 days) with no discernible differences in the proportion of tumor
      free survivors, indicating a lack of schedule dependency. The antibody-drug
      conjugate produced complete regressions, but the equivalent doses of free
      monomethylauristatin E or unconjugated antibody did not show anti-tumor effects.
      In addition, decreases in plasma tumor-derived human interleukin-8 coincided with
      tumor nodule disappearance. CONCLUSIONS: Short-term anti-tumor effects and long
      term effects (complete regression) were observed with CR011-vcMMAE, but not with
      the reference agents. These results suggest that CR011-vcMMAE may provide
      therapeutic benefit in malignant melanoma.

PMID- 17541594
TI  - Graph-theoretic methods for the analysis of chemical and biochemical networks. I.
      Multistability and oscillations in ordinary differential equation models.
AB  - A chemical mechanism is a model of a chemical reaction network consisting of a
      set of elementary reactions that express how molecules react with each other. In
      classical mass-action kinetics, a mechanism implies a set of ordinary
      differential equations (ODEs) which govern the time evolution of the
      concentrations. In this article, ODE models of chemical kinetics that have the
      potential for multiple positive equilibria or oscillations are studied. We begin
      by considering some methods of stability analysis based on the digraph of the
      Jacobian matrix. We then prove two theorems originally given by A. N. Ivanova
      which correlate the bifurcation structure of a mass-action model to the
      properties of a bipartite graph with nodes representing chemical species and
      reactions. We provide several examples of the application of these theorems.

PMID- 17541595
TI  - Graph-theoretic methods for the analysis of chemical and biochemical networks.
      II. Oscillations in networks with delays.
AB  - Delay-differential equations are commonly used to model genetic regulatory
      systems with the delays representing transcription and translation times.
      Equations with delayed terms can also be used to represent other types of
      chemical processes. Here we analyze delayed mass-action systems, i.e. systems in
      which the rates of reaction are given by mass-action kinetics, but where the
      appearance of products may be delayed. Necessary conditions for delay-induced
      instability are presented in terms both of a directed graph (digraph) constructed
      from the Jacobian matrix of the corresponding ODE model and of a species-reaction
      bipartite graph which directly represents a chemical mechanism. Methods based on
      the bipartite graph are particularly convenient and powerful. The condition for a
      delay-induced instability in this case is the existence of a subgraph of the
      bipartite graph containing an odd number of cycles of which an odd number are
      negative.

PMID- 17541596
TI  - Antiovarian antibodies in primary Sjogren's syndrome.
AB  - Our study aimed at screening patients with primary Sjogren's syndrome (pSs) for
      the presence of antiovarian antibodies (AOAs). Detection of AOAs in patients'
      sera was achieved by ELISA, using bovine ovarian extract for coating. Western
      blot analysis and immunohistochemistry were used to characterize the antibody
      targets in the extract and to determine their locus on the bovine ovary,
      respectively. Specific AOAs were detected in 27% of 37 patients (two with
      premature menopause) and in none of the controls. Immunoreactivity mainly resided
      in five proteins of the extract with molecular masses 42, 49, 55, 64 and 72 kDa,
      and it might be attributed to their carbohydrate components. The antibody targets
      were mainly located in the granulosa and theca interna cells of the follicle, and
      in the endothelial cells and fibroblasts of corpus luteum. The detection, for the
      first time, of AOAs in a significant percentage of patients with pSs may suggest
      autoimmune oophoritis, clinical or subclinical.

PMID- 17541597
TI  - Polymorphism of SFBB-gamma and its use for S genotyping in Japanese pear (Pyrus
      pyrifolia).
AB  - Japanese pear (Pyrus pyrifolia) exhibits the S-RNase-based gametophytic self
      incompatibility where the pollen-part determinant, pollen S, had long remained
      elusive. Recent identification of S locus F-box brothers (SFBB) in Japanese pear
      and apple suggested that the multiple F-box genes are the pollen S candidates as
      they exhibited pollen specific expression, S haplotype-specific polymorphisms and
      linkage to the S locus. In Japanese pear, three SFBBs were identified from a
      single S haplotype, and they were more homologous to other haplotype genes of the
      same group (i.e., alpha-, beta- and gamma-groups). In this study, we isolated new
      seven PpSFBB(-gamma) genes from different S genotypes of Japanese pear. These
      genes showed S haplotype-specific polymorphisms, however, sequence similarities
      among them were very high. Based on the sequence polymorphisms of the PpSFBB(
      gamma) genes, we developed a CAPS/dCAPS system for S genotyping of the Japanese
      pear cultivars. This new S genotyping system was found to not only be able to
      discriminate the S(1)-S(9), but also be suitable for identification of the mutant
      S(4sm) haplotype for the breeding of self-compatible cultivars, and detection of
      new S haplotypes such as S(k).

PMID- 17541598
TI  - Agrobacterium tumefaciens-mediated transformation of Narcissus tazzeta var.
      chinensis.
AB  - Phytoene synthase (PSY), as a key regulatory enzyme for carotene biosynthesis,
      plays an important role in regulating color formation in many species. In the
      present study, a protocol was developed for the transformation of Narcissus
      tazzeta var chinensis using Agrobacterium tumefaciens strain LBA4404 harboring a
      binary vector pCAMBIA1301 plasmid which contained an antisense phytoene synthase
      gene, a reporter beta-glucuronidase gene and a selectable marker hygromycin
      phosphotransferase gene. Effects of some factors on efficiency of transformation
      and regeneration were examined. Preculture of the explants for 6 days before
      inoculation enhanced the transient GUS expression. The addition of acetosyringone
      (AS) at 100 micromol l(-1) for inoculation and a period of 3 days co-cultivation
      yielded efficient transient GUS expression. Transformants were obtained through
      selection on MS medium containing 5 mg l(-1) 6-benzylaminopurine (BA), 0.1 mg l(
      1)alpha-naphthalene acetic acid (NAA) and 40 mg l(-1) hygromycin. The
      transformation frequency was 1.24% based on PCR analysis of gus gene. One or two
      copies of transgene were demonstrated in different transformations by Southern
      blotting analyses. Northern blotting results confirmed that the transcription of
      the endogenous psy gene in transgenic plants was inhibited or silenced. The
      method reported here provides new opportunities for improvement of quality traits
      of Narcissus tazzeta via genetic transformation.

PMID- 17541599
TI  - Characterization of an 18,166 EST dataset for cassava (Manihot esculenta Crantz)
      enriched for drought-responsive genes.
AB  - Cassava (Manihot esculenta Crantz) is a staple food for over 600 million people
      in the tropics and subtropics and is increasingly used as an industrial crop for
      starch production. Cassava has a high growth rate under optimal conditions but
      also performs well in drought-prone areas and on marginal soils. To increase the
      tools for understanding and manipulating drought tolerance in cassava, we
      generated expressed sequence tags (ESTs) from normalized cDNA libraries prepared
      from dehydration-stressed and control well-watered tissues. Analysis of a total
      of 18,166 ESTs resulted in the identification of 8,577 unique gene clusters
      (5,383 singletons and 3,194 clusters). Functional categories could be assigned to
      63% of the unigenes, while another approximately 11% were homologous to
      hypothetical genes with unclear functions. The remaining approximately 26% were
      not significantly homologous to sequences in public databases suggesting that
      some may be novel and putatively specific to cassava. The dehydration-stressed
      library uncovered numerous ESTs with recognized roles in drought-responses,
      including those that encode late-embryogenesis-abundant proteins thought to
      confer osmoprotective functions during water stress, transcription factors, heat
      shock proteins as well as proteins involved in signal transduction and oxidative
      stress. The unigene clusters were screened for short tandem repeats for further
      development as microsatellite markers. A total of 592 clusters contained 646
      repeats, representing 3.3% of the ESTs queried. The ESTs presented here are the
      first dehydration stress transcriptome of cassava and can be utilized for the
      development of microarrays and gene-derived molecular markers to further dissect
      the molecular basis of drought tolerance in cassava.

PMID- 17541600
TI  - The NF-kappaB/IL-6 pathway in metastatic androgen-independent prostate cancer:
      new therapeutic approaches?
AB  - The nuclear factor of kappa beta (NF-kappaB) transcription factor regulates the
      transcription of numerous genes including that of interleukin 6 (IL-6). The IL-6
      acts as an autocrine and paracrine growth factor of androgen-independent prostate
      cancer. An aberrant expression of the IL-6 gene and an increase in IL-6
      expression are detected in bone metastatic and hormone-refractory prostate
      cancer. IL-6 has been suggested to have a crucial role in the resistance to
      chemotherapy or hormonal therapy involving apoptotic cell death. The NF-kappaB/IL
      6 dependent pathways promote tumour-cell survival and in most situations protect
      cells against apoptotic stimuli. These data provide a rational framework for
      targeting NF-kappaB and IL-6 activity in novel biologically based therapies for
      aggressive and androgen independent prostate cancers.

PMID- 17541601
TI  - [Palliative radiotherapy for a retrobulbar metastasis from a urinary bladder
      carcinoma].
AB  - Retrobulbar metastases from transitional cell carcinoma of the urinary bladder
      are very rare. This is a case report of palliative radiotherapy successfully
      reducing acute clinical symptoms such as proptosis, dysfunction of the eye
      muscles and diplopia in a 50-year-old male patient with a retrobulbar metastasis
      from transitional cell carcinoma. Radiotherapy quickly ameliorated the proptosis
      and dysfunction of the eye muscles without side effects. The patient's quality of
      life was clearly improved.

PMID- 17541602
TI  - Developmental changes in ventricular myosin isoenzymes of the tammar wallaby.
AB  - Ventricular myosin in eutherian mammals undergoes a perinatal change in response
      to a sharp rise in thyroid hormone levels during development. In this
      investigation, changes in ventricular myosin heavy chains (MyHCs) of the tammar
      wallaby (Macropus eugenii) from early pouch life to adulthood were analysed using
      native gel electrophoresis, SDS-PAGE and western blotting. Adult wallaby
      ventricle showed three myosin isoenzymes, V(1), V(2) and V(3); western blots
      using specific anti-alpha-MyHC and anti-beta-MyHC antibodies showed their MyHC
      compositions to be alphaalpha, alphabeta and betabeta, respectively. Ventricular
      muscle in early pouch joeys expressed predominantly beta-MyHC. Up to 200 days,
      the time of initial pouch exit, alpha-MyHC content was around 5%. Thereafter,
      there was a sharp increase of alpha-MyHC expression to 35% by 242 days of age,
      eventually falling back to 23% in the adult. These changes correlate with known
      surges in plasma levels of thyroid hormones around pouch exit. The results
      suggest that ventricular myosins in a marsupial mammal also undergo a
      developmental change, and that marsupial ventricular myosins are thyroid
      responsive as in eutherians. The increased alpha-MyHC expression empowers the
      heart to meet the enhanced cardiovascular demands of out-of-pouch activity and
      the thermogenic action of thyroid hormones.

PMID- 17541603
TI  - Whitebellied sunbirds (Nectarinia talatala, Nectariniidae) do not prefer
      artificial nectar containing amino acids.
AB  - Amino acids are the most abundant class of compounds in nectar after sugars. Like
      its sugar concentration, the amino acid concentration of nectar has been linked
      to pollinator type, and it has been suggested that amino acid concentrations are
      high in the floral nectars of plant species pollinated by passerine birds
      compared to those pollinated by hummingbirds. We investigated the feeding
      response of whitebellied sunbirds (Nectarinia talatala) to the inclusion of amino
      acids in artificial nectar (0.63 M sucrose solution). The response to asparagine,
      glutamine, phenylalanine, proline, serine and valine, amino acids commonly found
      in floral nectars, was tested individually and using a mixture of all six amino
      acids, at two different concentrations (2 and 15 mM). Sunbirds showed no
      significant preference for amino acids in nectar, or avoided them, especially at
      the higher concentration. We discuss these findings in the light of the nitrogen
      requirements of nectarivorous birds and data on amino acids in floral nectars.

PMID- 17541604
TI  - Hemangiopericytoma of thoracic spine: a rare bony tumor.
AB  - CASE REPORT: We report the case of a 16-year-old girl who developed
      hemangiopericytoma of the thoracic spine; the main clinical symptoms were of
      spastic paraparesis with sensory involvement and uro-fecal incontinence. She was
      initially put on antitubercular treatment keeping in mind the endemicity of
      tuberculosis in the region. When she deteriorated on conservative management, she
      was operated upon, and the histopathological report was suggestive of
      hemangiopericytoma. MATERIALS AND METHODS: Additional immunocytochemistry was
      performed in the paraffin-embedded tumor sections. CONCLUSIONS: An extremely rare
      case of primary epidural malignant hemangiopericytoma of the thoracic spinal
      column is described. It is a rare tumor, which is locally aggressive, and a
      potentially malignant tumor. The tumor is more commonly found in the cranium, and
      spinal involvement is rare, and only few case reports could be retrieved from the
      literature. We discuss the clinical profile, management, and outcome of spinal
      hemangiopericytomas along with pertinent review of the literature.

PMID- 17541605
TI  - Endoscopic options in management of posterior third ventricular tumors.
AB  - OBJECTIVE: A spectrum of both radiosensitive and radio-resistant lesions occurs
      in the region of the posterior third ventricle (PTV). Most of these are
      associated with hydrocephalus requiring a cerebrospinal fluid diversion
      procedure. The present study aims to assess the effectiveness of endoscopic
      biopsy and third ventriculostomy (ETV) in these patients. MATERIALS AND METHODS:
      Twenty-four patients with PTV lesions with moderate to severe hydrocephalus were
      managed prospectively. All patients underwent ETV and biopsy of the lesion during
      the same procedure. The ETV could be performed in all patients, where as in 23, a
      successful biopsy could be obtained. The ETV was successful in 22 patients; it
      failed in 2 patients requiring shunt insertion. A positive biopsy was obtained in
      all the patients (pinealocytoma 4, pinealoblastoma 10, embryonal cell carcinoma
      1, germinoma 2, oligodendroglioma 1, astrocytoma 2, tuberculoma 4). All patients
      were subsequently managed with further surgery, radiation, and chemotherapy
      either alone or in combination depending on the pathology. One patient with a
      tumor bed hematoma required clot evacuation. The follow-up period ranged from 12
      to 36 months. Two patients died, one during hospital stay with a tumor bed
      hematoma and another at 6 months follow-up due to extensive leptomeningeal
      spread. CONCLUSIONS: The high yield of endoscopic biopsy (100%) and success of
      ETV (91%) emphasizes its role in management of the diverse group of PTV lesions
      in arriving at the optimal definitive management.

PMID- 17541606
TI  - Adolescent lumbar disc disease: findings and outcome.
AB  - BACKGROUND: Lumbar disc herniation is mainly a disease of elderly people as
      degenerative changes progress with age. RESULTS AND DISCUSSION: Present
      retrospective analysis was performed on 742 patients of lumbar disc disease
      operated over 11 years. Of 742 cases aged 20 years or less, 25 has been evaluated
      to see the clinical features, radiological features, operative findings, and
      outcome of lumbar disc surgery. The incidence of lumbar disc herniation in
      pediatric and adolescent populations was 3.5% (aged 20 years or less). All
      patients presented with low back pain with or without radiculopathy (n = 25).
      Diagnosis was easily made on magnetic resonance imaging. Gross degenerative
      changes in disc and end plates were uncommon (16%) in this population. The trauma
      may not be a predisposing factor in most of them. In 88% (n = 22) of the cases,
      only 1 level was affected; the commonest was L4-5 (n = 13). Disc herniation was
      centrolateral in 72% (n = 18) and central in 28% (n = 7). Disc was mostly soft,
      hydrated, and rubbery in 92% (n = 23). Disc herniation were subligamentous in 80%
      (n = 20) and extruded in 4% (n = 1). Sixteen percent (n = 4) of the patients had
      disc bulge with intact annulus. CONCLUSIONS: Operative intervention in the form
      of simple discectomy offers good result in 92% (n = 23) cases irrespective of
      approach and method. Longer follow-up is mandatory because the chances of
      recurrence or another level involvement cannot be denied.

PMID- 17541607
TI  - Abubakr Muhammad Ibn Zakaria Razi, Rhazes (865-925 AD: ).

PMID- 17541608
TI  - "Anal angina"--pelvic sepsis and streptococcal toxic shock syndrome after
      rectoscopy and mucosal biopsy.

PMID- 17541609
TI  - [Johann Lukas Schonlein (1793-1864). The degraded honorary citizen].

PMID- 17541610
TI  - WHO grade associated downregulation of MHC class I antigen-processing machinery
      components in human astrocytomas: does it reflect a potential immune escape
      mechanism?
AB  - Defects of major histocompatibility complex (MHC) class I antigen-processing
      machinery (APM) components have been shown to contribute to immune escape of
      malignant cells. We investigated the expression of APM components in astrocytomas
      without detectable defects in HLA class I antigen expression and correlated it
      with grade of malignancy. Quantitative immunohistochemical analysis of
      astrocytomas revealed reduced expression of the cytosolic proteasome subunit low
      molecular weight protein 2 (LMP2), the endoplasmatic reticulum (ER) transporter
      associated with antigen processing-1 (TAP1), and the ER chaperone beta2
      microglobulin (beta2m) in astrocytoma cells when compared to astrocytes from
      nonpathological brain. Among human WHO grade II-IV astrocytomas, downregulation
      of LMP2, TAP1 and beta2m correlated with grade of malignancy. Furthermore,
      astrocytoma cell lines (n = 12) expressed all APM components analyzed at levels
      comparable to dendritic cells (DC), which were used for comparative purposes.
      However, upregulation of beta2m after stimulation with inflammatory cytokines was
      significantly lower in astrocytoma cell lines than in control cells. Our results
      support the hypothesis that coordinated downregulation or impaired upregulation
      of certain HLA class I APM components may serve as a mechanism for astrocytoma
      cells to evade the host's immune response, even if HLA class I antigen surface
      expression is not altered.

PMID- 17541611
TI  - Intra-articular hip viscosupplementation with synthetic hyaluronic acid for
      osteoarthritis: efficacy, safety and relation to pre-injection radiographs.
AB  - OBJECTIVE: The aim of this study was to determine the efficacy and safety of
      viscosupplementation with synthetic hyaluronic acid to the hip joint and to
      determine if there was any relation to pre-injection radiographic changes of
      osteoarthritis (OA). METHODS: Three Suplasyn injections were performed each to 15
      hips with OA. Standing antero-posterior radiographs of the pelvis were performed
      prior to injection and scored according to Kelgren and Lawrence grades along with
      recordings of the minimum joint space width. Harris Hip Scores (HHS) which
      contain a component for pain, function, activities, absence of deformity and
      range of motion were recorded pre-injection and at 3 and 6 months. RESULTS: We
      established that at 3 months the HHS is significantly higher (P < 0.05). At 6
      months, four hips had been excluded as they has went on to total hip arthroplasty
      (these hips showed a lower HHS at 3 months). For the remaining hips the HHS was
      highly significantly increased (P < 0.001). No side effects or complications were
      observed. Analysis of the pre-injection radiographs showed a trend towards a
      bigger increase in HHS with less radiographic OA changes. CONCLUSIONS:
      Viscosupplementation performed under fluoroscopic guidance is an effective and
      safe method of treating hip OA and appears to be more efficacious in those with
      less radiographic changes of OA.

PMID- 17541612
TI  - Proximal oblique-domed osteotomy of the first metatarsal for the treatment of
      hallux valgus associate with flat foot: effect to the correction of the
      longitudinal arch of the foot.
AB  - INTRODUCTION: Flat foot and/or metatarsal primus varus are the major causes of
      hallux valgus, and it is important to correct these deformities in order to
      prevent the recurrence of this condition. We demonstrate the clinical and
      radiological assessment of the correction of hallux valgus, metatarsal primus
      varus, and flat foot after proximal oblique-domed osteotomy of the metatarsus
      with distal soft tissue reconstruction. MATERIALS AND METHODS: Twenty-seven feet
      of 22 patients with moderate or severe hallux valgus who had undergone proximal
      oblique-domed osteotomy were studied. After the adductor hallucis tendon was cut
      at the attachment of the proximal phalanx and at the sesamoid bone, the osteotomy
      was performed 3 cm dorsal-distal to the metatarsocuneiform joint to transfer
      distal fragment approximately 5 mm in the plantar direction, and rotated
      laterally decreasing the first-second intermetatarsal angle to 5 degrees.
      RESULTS: The mean AOFAS score was 54.1 +/- 2.8 points at pre-operation and 92.8
      +/- 4.8 points at the most recent follow-up (P < 0.0001). Significant improvement
      was seen between the hallux valgus angle (P < 0.0001), first-second
      intermetatarsal angle (P < 0.0001), first-fifth intermetatarsal angle (P <
      0.0001), talar pitch (P = 0.0032), and calcaneal plantar angle (P = 0.0327)
      before surgery and at one year after surgery. The average improvement of the
      talar pitch and calcaneal plantar angle was 2.6 +/- 1.4 and 2.4 +/- 1.5 degrees,
      respectively. CONCLUSION: This study suggest that proximal oblique-domed
      osteotomy of the metatarsal as a surgical procedure for the treatment of moderate
      or severe hallux valgus with flat foot can be recommended to correct the
      longitudinal arch of the foot and the first-second intermetatarsal angle.

PMID- 17541613
TI  - The clinical significance of impaction at the femoral neck fracture site in the
      elderly.
AB  - INTRODUCTION: Factors influencing clinical outcomes of osteosynthesis for elderly
      patients with Garden stage I and II femoral neck fractures are not well
      understood. MATERIALS AND METHODS: To determine the factors influencing the
      clinical outcomes of in situ osteosynthesis in non-displaced femoral neck
      fractures in the elderly, radiographs and clinical data of patients were
      retrospectively analyzed. The subjects were 49 patients with femoral neck
      fractures (Garden stages I and II), who underwent osteosynthesis, with correctly
      inserted screws and with more than 2 years of follow up. The relationships
      between preoperative anteroposterior X-ray parameters including Garden stage, the
      presence or absence of spikes, the Singh grade, the Garden alignment index, the
      degree of impaction at the fracture site (the capital impaction index) and
      postoperative outcomes were analyzed. RESULTS: Among the 49 cases, there were
      eight unsuccessfully treated patients, two with non-union and six with late
      segmental collapse. The "without spikes" fracture type (P < 0.05) and the degree
      of capital impaction when the capital impaction index (P < 0.0001) was greater
      than the mean plus the standard deviation, were significantly associated with
      unsuccessful outcomes. CONCLUSION: Excessive shortening at the fracture site on
      the anteroposterior radiograph in the femoral neck fracture of Garden stages I
      and II can be used to predict poor outcomes from in situ osteosynthesis.

PMID- 17541614
TI  - Tissue engineering of the anterior cruciate ligament: a new method using
      acellularized tendon allografts and autologous fibroblasts.
AB  - INTRODUCTION: The availability of autogenous tendons (middle part of patellar
      tendon, semitendinosus/gracilis, or quadriceps tendon) for cruciate ligament
      reconstructions is restricted and related to withdrawal morbidity. Allografts and
      synthetic ligament materials often show problems regarding long-term stability
      and immunological reactions. Therefore, the aim of this study was to develop and
      characterize a new scaffold based on acellular allografts seeded with autologous
      cells for tissue engineering of the anterior cruciate ligament (ACL). MATERIALS
      AND METHODS: Semitendinosus tendons of New Zealand White (NZW) rabbits were
      harvested and acellularized using the detergent sodium dodecyle sulfate (SDS) as
      the main ingredient. After that, cultured (37 degrees C, 5% CO(2), medium) dermal
      fibroblasts were injected into the tendons. These constructs were further
      cultivated for 4, 7, or 14 days under the same culture conditions. Native,
      acellular, and seeded tendons underwent biomechanical testing (ultimate load to
      failure [N], stiffness [N/mm], and elongation [%], each n = 9] and histological
      hematoxylin-eosin (H.E.) staining. Detailed immunohistochemical (collagen I, III,
      IV, VI, pro-collagen I, versican, and vimentin) analyses were conducted to detect
      changes in the composition and structure of the extracellular matrix (ECM) after
      acellularization. RESULTS: Histologically, a cell-free, crimped slack tendon
      structure after acellularization and a good integration of the cells after
      injection (4, 7, and 14 days) were seen. Metabolic activity of the seeded cells
      was demonstrated by positive immunohistochemical staining for pro-collagen I,
      which was negative in nonseeded constructs. Major differences in staining
      patterns of the various other ECM components were not observed. Biomechanically,
      the maximum load to failure of these tendons was comparable to native tendons (P
      = 0.429; native 134.5 +/- 12.9 N; acellular 118.5 +/- 7.3 N; seeded 132.3 +/- 5.6
      N). Stiffness and elongation were comparable between native and acellular
      tendons, but differed significantly after seeding (P < 0.001). CONCLUSION: The
      described method is suitable to make tendons completely cell free without
      changing their major biomechanical properties. Preservation of the ECM and of the
      collagen fiber structure by this method should give an ideal environment for
      autologous cell integration and metabolic activity in contrast to other
      approaches for tissue acellularization. The cell disruption and extraction of
      cell detritus should minimize adverse immunogenic reactions.

PMID- 17541615
TI  - Increased expression of 2'5'oligoadenylate synthetase and double-stranded RNA
      dependent protein kinase messenger RNAs on affected skin of systemic sclerosis
      patients.
AB  - Scleroderma or systemic sclerosis (SSc) is an autoimmune disorder of unknown
      aetiology characterized by excessive collagen synthesis and subsequent deposition
      on the skin and various internal organs. Interferons (IFNs) are well-known
      immunomodulators and inhibitors of collagen production. However, IFN therapy has
      been implicated in the development or exacerbation of several autoimmune
      diseases, including SSc. We analyzed the expression of several interferon
      stimulated genes (ISGs) in affected skin of SSc patients (skin tissue and
      cultured skin fibroblasts). A set of ISGs (PKR, 2'5'OAS, MxA, and 6-16) was
      analyzed by real-time PCR using RNA extracted from cultured skin fibroblasts and
      skin tissue of normal individuals and SSc patients. Both normal and SSc affected
      skin cultured fibroblasts were sensitive to the IFN treatment and presented
      similar levels of all ISGs tested. However, PKR and 2'5'OAS mRNA expression
      levels were significantly higher in the affected skin tissue of SSc patients when
      compared to normal controls. These data suggest that the IFN system plays a role
      in the pathogenesis of SSc.

PMID- 17541616
TI  - Triple synchronous primary cervical, endometrial and ovarian cancer with four
      different histologic patterns.
AB  - BACKGROUND: Double synchronous primary cancers of gynecological cancers is a
      common event. However, triple synchronous primary gynecological cancers is an
      extremely rare event. CASE: A 50-year-old woman, para 0-0-0-0 was admitted to the
      hospital with a complaint of menorrhagia for 2 months. The preoperative
      evaluation and diagnosis was myoma uteri with bilateral ovarian tumor. Subtotal
      hysterectomy with bilateral salpingo-oophorectomy, and omentectomy were
      performed. The postoperative and pathologic findings were adenosquamous carcinoma
      of the endocervix, adenocarcinoma of the endometrium, low malignant potential of
      the right ovary and mucinous cystadenocarcinoma of the left ovary. She received a
      complete course of whole pelvic radiation. Unfortunately, she died from pulmonary
      embolism. CONCLUSION: The occurrence of triple synchronous gynecological cancers
      is a rare and unique event deserving further studies.

PMID- 17541617
TI  - Clinicopathological evaluation of 59 cases of fetal death.
AB  - OBJECTIVE: The purpose of this study has been assessing the determinants of
      stillbirth among the newborns of the Verona University Obstetrics Department.
      MATERIALS AND METHODS: A total of 59 stillbirth cases, observed between January
      2000 and June 2006, were retrospectively studied. WHO definition for stillbirth
      was adopted as the inclusion criterion. Clinical files, feto-maternal laboratory
      data, feto-placental pathology findings as well as delivery mode and
      circumstances were all systematically reviewed. RESULTS: The 59 observed cases
      correspond to an incidence of 9.8 stillbirths/year, which, considering the
      institutional delivery rate, correspond to 5.4 cases per 1000 births. Frequent
      relevant conditions associated with stillbirth were intrauterine growth
      restriction (15.2%), congenital fetal anomalies (13.5%), various maternal
      diseases (21.0%); no cause of fetal demise could be found in 10/59 (17.0%) cases,
      which were classified as unexplained. Most deliveries were successfully induced
      with prostaglandins except 11 cases (19.0%) which required a C-section due to
      severe maternal conditions associated with the fetal loss. CONCLUSION: Thorough
      investigation of each individual stillbirth case, by means of an integrated study
      protocol, along with the Pathologist's close collaboration, allows identification
      of a likely cause in the majority of cases. Better knowledge of unexpected fetal
      loss is the premise for better parental counselling and for prevention of
      recurrences.

PMID- 17541618
TI  - Iron supplementation in pregnancy--does the preparation matter?
AB  - OBJECTIVE: To assess the use, side effects and discontinuation rates of iron
      preparations during pregnancy. DESIGN: Six hundred and twelve randomly selected
      postpartum women completed a questionnaire on iron supplement use in the second
      and third trimesters. RESULTS: Of the 517 women (84.5%) reported using iron
      supplements, 453 were eligible for the study. The most common preparation was
      ferrous fumarate (46.8%, P < 0.01), followed by ferrous sulfate (31.8%), ferric
      polymaltose (12.4%), and ferric bisglycinate (7.3%). Almost half the participants
      (45%) reported at least one adverse effect, especially constipation (27.4%, P <
      0.01), nausea (10.8%). Multivitamin preparations and ferric bisglycinate were
      associated with the fewest side effects (23.7, 21.2% respectively, P < 0.01), and
      ferrous fumarate and immediate-release ferrous sulfate with the most (56.3, 53.7%
      respectively). Eighty-three women discontinued their originally prescribed iron
      preparation, mainly (89%) due to side effects. Discontinuation rates were lowest
      for the multivitamin and ferric bisglycinate (10.5, 9.1%, respectively). In most
      cases, the specific preparation was recommended by the women's physician (76%).
      CONCLUSION: Ferrous fumarate-containing multivitamin preparations and ferric
      bisglycinate, although infrequently recommended as the first-line of iron
      supplementation, may be associated with less side effects and better compliance.

PMID- 17541619
TI  - Salmonella ovarian abscess following travel diarrhoea episode.
AB  - The case of a 36-year-old woman with a non-typhoidal Salmonella ovarian abscess
      is reported. Remarkably, pathological findings of the oophorectomy piece did not
      demonstrate any pre-existing ovarian abnormalities.

PMID- 17541620
TI  - Comparative analysis of the epithelium stroma interaction of acquired middle ear
      cholesteatoma in children and adults.
AB  - In the clinical setting, pediatric cholesteatomas frequently behave more
      aggressively than similar lesions in adults. The reason for the difference in
      behavior is still unclear. The purpose of the present study was to investigate
      the cell to cell and epithelial-stroma interaction of acquired cholesteatoma in
      adults and children and search for differences on the cellular level, which might
      explain the different behavior of these lesions. Operative specimens of 54
      patients [40 adults (average age of 39.7 years), 14 children (average age of 8.3
      years)] who underwent primary surgery for an acquired cholesteatoma of the middle
      ear were examined by histopathology and DNA-image cytometry (DNA-ICM).
      Immunohistochemical investigations included expression of proliferation markers
      (proliferation cell nuclear antigen and MIB-1) along with cell surface markers
      reflecting the cell-to-cell interaction (i.e. alpha1beta6-integrin, E-cadherin, I
      CAM = CD54), and the epithelial to stroma interaction (i.e. alphav and beta3
      intergin chains, V-CAM = CD106, CD44v6 and fibronectin). Pediatric cholesteatomas
      demonstrated higher incidence of acute inflammation and more extensive disease
      relative to those from the adults. Indices of DNA-ICM, however, revealed normal
      diploid DNA content in both groups. Higher proliferation scores occurred in the
      pediatric group compared to adult cholesteatoma. Cell surface markers and cell
      adhesion molecules were equally expressed in both groups except alpha1beta6
      integrin and fibronectin, which were over expressed in pediatric cholesteatomas.
      Statistically, however, these differences showed only a trend towards
      significance. According to the results of the present study, pediatric and adult
      cholesteatomas do not show any marked differences on the cellular level. Thus the
      observed clinical more aggressive behavior of pediatric cholesteatoma is likely
      due to other secondary factors such as more intense inflammation, disturbed
      middle ear ventilation or the diminished calcium salt content of pediatric bone.

PMID- 17541621
TI  - Prolongation of corneal allograft survival by CTLA4-FasL in a murine model.
AB  - BACKGROUND: To investigate the therapeutic effect of CTLA4-FasL-B7 costimulatory
      pathway blockage-on graft survival in a murine model of corneal transplantation.
      METHODS: Orthotopic penetrating keratoplasty was performed on BALB/c mice. The
      mice were randomized into four groups: the isograft group, untreated allograft
      group, cyclosporine A drug delivery system (CsA DDS)-anterior chamber implanted
      group, and 10 microg/mL CTLA4-FasL-treated group. Allografts were from C57BL/6
      mice. Survival time of corneal grafts was evaluated. Immunohistological method
      and TdT-mediated dUTP Nick End Labeling (TUNEL) were applied for the detection of
      CD4+ T cells and apoptotic cells in corneal transplants. To assess whether
      peripheral immune tolerance appeared after the treatment of CTLA4-FasL, CsA DDS
      implanted- and CTLA4-FasL-treated BALB/c mice with clear grafts received skin
      allografts at 4 weeks after keratoplasty, and the status of corneal transplants
      were observed when skin grafts were rejected. RESULTS: Allografts in the CTLA4
      FasL group (median survival time [MST] = 106 days, p = 0.0042) and the CsA DDS
      group (MST = 60 days, p = 0.0037) revealed extending survival time, compared with
      that in the untreated allograft group (MST = 14 days). There were significantly
      fewer CD4-positive T cells in both the isograft group and the CsA DDS group. In
      the untreated allograft group, the number of CD4+ T cells gradually increased
      from day 1 until the final day of observation (day 21). By contrast, it reached a
      peak on day 7 and then absolutely reduced in the CTLA4-FasL group. Many apoptotic
      cells were detected on day 7 in the CTLA4-FasL group, but very few were seen in
      the other groups. Within 30 days of skin-graft rejection, previously healthy and
      long-standing corneal grafts became rejected in the CsA DDS group but remained
      clear in the CTLA4-FasL group. CONCLUSIONS: CTLA4-FasL can prolong the survival
      time of corneal allografts in mice, exerting a negative regulation on T-cell
      activation simultaneously by blocking B7 costimulatory signals and inducing Fas
      FasL apoptotic pathway. Due to the adjunctive role of FasL, it also appears to be
      a potential activity of tolerance induction through T-cell apoptotic pathways.

PMID- 17541622
TI  - MUC5AC overexpression in tear film of neonates.
AB  - BACKGROUND: Full-term neonates produce tears normally, but neonatal tear film is
      modified to resist evaporation with a thick lipid layer that allows lower
      spontaneous blink rates. This adaptation presumably prevents drying of the ocular
      surface during long inter-blink periods. However, tear-film stability is not only
      based on the integrity of the lipid layer, but also reflects properties of the
      underlying mucus layer. Characteristics of the neonatal mucus tear-film layer
      have not yet been described. MATERIALS AND METHODS: Tear samples were obtained
      from eight full-term healthy neonates (four males, four females, mean age 1.7 +/-
      0.5 days) and eight healthy adult controls (four males, four females, mean age
      26.3 +/- 2.5 years). Characterization of tear samples' total proteins was
      obtained by spectrophotometry. Western blot for major secretory mucin MUC5AC was
      performed on the samples. Blink rate in the neonates and adults enrolled in the
      study was also observed and recorded. RESULTS: Using the same procedure, the
      amount of tears collected was significantly greater in adults than in neonates (p
      < .01). Western Blot performed on neonatal tear samples showed a significant
      76.8% increase in the expression of major secretory mucin MUC5AC as compared to
      healthy adult controls (p < .001). Mean blink rate recorded in neonates was
      significantly lower than in adults (p < .001), with a mean 1.6 +/- 0.5 blinks per
      minute and a mean interblink time of 33 +/- 9 seconds. DISCUSSION: As far as we
      are aware this is the first description of the mucus tear-film layer in neonates.
      The greater tear-film stability in neonates has been so far attributed to a
      thicker lipid layer. In our study, we show that a concomitant increase in MUC5AC
      protein expression in tears is present and may contribute to this greater
      stability; therefore, both mucus and lipid layer should be considered while
      evaluating tear film stability in neonates.

PMID- 17541623
TI  - CD4+CD25+Tregs express an increased LAG-3 and CTLA-4 in anterior chamber
      associated immune deviation.
AB  - BACKGROUND: Regulatory CD4(+)CD25(+) T cells have been proven to be essential for
      maintenance of peripheral tolerance and autoimmune diseases. ACAID is a model of
      immune privilege in the eye. Relatively little is known about the role and
      phenotype of these regulatory CD4(+)CD25(+) T cells in ACAID. METHODS: Injection
      of OVA into the anterior chamber of BALB/C mice was performed to induce ACAID.
      The frequencies of splenic CD4(+)CD25(+) Tregs and the expression of CTLA-4 and
      LAG-3 on these cells were determined by flow cytometry. Magnetic cell sorting was
      used to isolate CD4(+)CD25(+) and CD4(+)CD25(-)T cells. The function of
      CD4(+)CD25(+) T cells was detected by in vitro immunosuppression assays and in
      vivo adoptive transfer. RESULTS: ACAID was successfully induced following an i.c.
      injection of OVA. Frequencies of CD4(+)CD25(+) and Tregs were significantly
      increased in ACAID mice as compared to those in controls. The CD4(+)CD25(+) T
      cells stimulated with OVA in ACAID mice showed a stronger suppressive ability in
      vitro than those seen in non-ACAID mice. CD4(+)CD25(+) T cells from ACAID mice,
      but not from non-ACAID mice, were able to suppress DTH responses in an antigen
      specific manner following adoptive transfer. The frequencies of CTLA-4 or LAG-3
      on Tregs in ACAID mice were higher as compared with those in naive mice.
      CONCLUSION: Splenic CD4(+)CD25(+)Foxp3(+)T cells expressing CTLA4 and LAG3 play
      an important role in the induction of ACAID.

PMID- 17541624
TI  - Distribution of lactate dehydrogenase in healthy and degenerative canine stifle
      joint cartilage.
AB  - In dogs, degenerative joint diseases (DJD) have been shown to be associated with
      increased lactate dehydrogenase (LDH) activity in the synovial fluid. The goal of
      this study was to examine healthy and degenerative stifle joints in order to
      clarify the origin of LDH in synovial fluid. In order to assess the distribution
      of LDH, cartilage samples from healthy and degenerative knee joints were
      investigated by means of light and transmission electron microscopy in
      conjunction with immunolabeling and enzyme cytochemistry. Morphological analysis
      confirmed DJD. All techniques used corroborated the presence of LDH in
      chondrocytes and in the interterritorial matrix of healthy and degenerative
      stifle joints. Although enzymatic activity of LDH was clearly demonstrated in the
      territorial matrix by means of the tetrazolium-formazan reaction, immunolabeling
      for LDH was missing in this region. With respect to the distribution of LDH in
      the interterritorial matrix, a striking decrease from superficial to deeper
      layers was present in healthy dogs but was missing in affected joints. These
      results support the contention that LDH in synovial fluid of degenerative joints
      originates from cartilage. Therefore, we suggest that (1) LDH is transferred from
      chondrocytes to ECM in both healthy dogs and dogs with degenerative joint disease
      and that (2) in degenerative joints, LDH is released from chondrocytes and the
      ECM into synovial fluid through abrasion of cartilage as well as through enhanced
      diffusion as a result of increased water content and degradation of collagen.

PMID- 17541625
TI  - Acute effects on heart rate variability when exposed to hand transmitted
      vibration and noise.
AB  - OBJECTIVES: This study investigates possible acute effects on heart rate
      variability (HRV) when people are exposed to hand transmitted vibration and noise
      individually and simultaneously. METHODS: Ten male and 10 female subjects were
      recruited by advertisement. Subjects completed a questionnaire concerning their
      work environment, general health, medication, hearing, and physical activity
      level. The test started with the subject resting for 15 min while sitting down.
      After resting, they were exposed to one of four exposure conditions: (1) only
      vibration; (2) only noise; (3) both noise and vibration; or (4) a control
      condition of exposure to the static load only. All four exposures lasted 15 min
      and the resting time between the exposures was 30 min. A continuous
      electrocardiogram (ECG) signal was recorded and the following HRV parameters were
      calculated: total spectral power (P(TOT)); the spectral power of the very low
      frequency component (P(VLF)); the low frequency component (P(LF)); the high
      frequency component (P(HF)); and the ratio LF/HF. RESULTS: Exposure to only
      vibration resulted in a lower P(TOT) compared to static load, whereas exposure to
      only noise resulted in a higher P(TOT). The mean values of P(TOT), P(VLF), P(LF),
      and P(HF) were lowest during exposure to vibration and simultaneous exposure to
      vibration and noise. CONCLUSIONS: Exposure to vibration and/or noise acutely
      affects HRV compared to standing without these exposures. Being exposed to
      vibration only and being exposed to noise only seem to generate opposite effects.
      Compared to no exposure, P(TOT) was reduced during vibration exposure and
      increased during noise exposure.

PMID- 17541626
TI  - Trait anxiety and modeled exposure as determinants of self-reported annoyance to
      sound, air pollution and other environmental factors in the home.
AB  - OBJECTIVES: We examined to what degree annoyance ratings to noise, air pollution
      and other common environmental factors in the home environment could be
      considered to mirror personality disposition in terms of habitual anxiety level
      and, when appropriate, objectively modeled noise and nitrogen emission (NOx).
      METHODS: A trait anxiety scale was introduced in a cross-sectional public health
      survey with 2,856 respondents. Of these, 705 had self-reported asthma and the
      rest constituted gender-matched referents. Annoyance to ten specific factors in
      the residential environment, mainly focusing on source-specific noise and air
      pollution, was assessed on a six-point likert scale. A-weighted energy equivalent
      continuous sound pressure level during a full day (24 h; L (Aeq,24)) as well as
      annual average NOx levels (microg/m(3)) at the residential address were modeled
      with high resolution, using a road data base and a detailed emission data base
      for NOx. RESULTS: The two most prevalent complaints were annoyance to traffic
      noise and sounds from neighbors, which was reported by about 8% of the
      participants. Unadjusted logistic regression analyses using the continuous trait
      anxiety score as a predictor showed positive associations with ratings of
      annoyance from total traffic noise, sounds from neighbors, sound from
      ventilation, exhaust fumes from traffic, sounds from other installations, and
      vibrations from traffic (ORs between 1.37 and 2.14). Modeled noise and NOx
      exposure were positively related with annoyance to traffic noise and exhaust
      fumes, respectively. Adjustment of the trait anxiety scores for other individual
      characteristics and potential determinants did not change the overall pattern of
      results. CONCLUSION: Trait anxiety scores were often mirrored in ratings of
      annoyance, which suggests caution when using annoyance reports either as a
      surrogate measure for environmental exposure on the individual-level in
      epidemiologic studies or when studying the moderating effects of annoyance on
      health outcomes.

PMID- 17541627
TI  - The lipid connection-regulation of voltage-gated Ca(2+) channels by
      phosphoinositides.
AB  - Recent findings have revealed a pivotal role for phospholipids
      phosphatidylinositol -4,5-biphosphate (PIP(2)) and phosphatidylinositol -3,4,5
      trisphosphate (PIP(3)) in the regulation of high voltage-activated (HVA) Ca(2+)
      channels. PIP(2) exerts two opposing actions on HVA Ca(2+) channels: It
      stabilizes their activity but also produces a voltage-dependent inhibition that
      can be antagonized by protein kinase A (PKA) phosphorylation. PIP(2) depletion
      and arachidonic acid together mediate the slow, voltage-independent inhibition of
      HVA Ca(2+) channels by G( q/11 )-coupled receptors in neurons. A sufficient level
      of plasma membrane PIP(2) also appears to be necessary for G( betagamma )
      mediated inhibition. On the other hand, increased production of PIP(3) by PI-3
      kinases promotes trafficking of HVA Ca(2+) channels to the plasma membrane. This
      review discusses these findings and their implications.

PMID- 17541628
TI  - The citrus fruit proteome: insights into citrus fruit metabolism.
AB  - Fruit development and ripening are key processes in the production of the
      phytonutrients that are essential for a balanced diet and for disease prevention.
      The pathways involved in these processes are unique to plants and vary between
      species. Climacteric fruit ripening, especially in tomato, has been extensively
      studied; yet, ripening of non-climacteric fruit is poorly understood. Although
      the different species share common pathways; developmental programs,
      physiological, anatomical, biochemical composition and structural differences
      must contribute to the operation of unique pathways, genes and proteins. Citrus
      has a non-climacteric fruit ripening behavior and has a unique anatomical fruit
      structure. For the last few years a citrus genome-wide ESTs project has been
      initiated and consists of 222,911 clones corresponding to 19,854 contigs and
      37,138 singletons. Taking advantage of the citrus database we analyzed the citrus
      proteome. Using LC-MS/MS we analyzed soluble and enriched membrane fractions of
      mature citrus fruit to identify the proteome of fruit juice cells. We have
      identified ca. 1,400 proteins from these fractions by searching NCBI-nr (green
      plants) and citrus ESTs databases, classified these proteins according to their
      putative function and assigned function according to known biosynthetic pathways.

PMID- 17541629
TI  - Mitogen-activated protein kinase OsMPK6 negatively regulates rice disease
      resistance to bacterial pathogens.
AB  - Mitogen-activated protein kinase (MAPK) cascades play important roles in diverse
      developmental and physiological processes of plants, including pathogen-induced
      defense responses. Although at least 17 rice MAPKs have been identified and more
      than half of these MAPK genes have been shown to be pathogen or elicitor
      responsive, the exact role of most of the MAPKs in host-pathogen interaction is
      unknown. Here we report that OsMPK6 is an important regulator in rice disease
      resistance. Suppressing OsMPK6 or knocking out of OsMPK6 enhanced rice resistance
      to different races of Xanthomonas oryzae pv. oryzae, causing bacterial blight,
      one of the most devastating diseases of rice worldwide. The resistant plants
      showed increased expression of a subset of defense-responsive genes functioning
      in the NH1 (an Arabidopsis NPR1 orthologue)-involved defense signal transduction
      pathway. These results suggest that OsMPK6 functions as a repressor to regulate
      rice defense responses upon bacterial invasion.

PMID- 17541630
TI  - Characterization of 1-aminocyclopropane-1-carboxylate (ACC) deaminase containing
      Methylobacterium oryzae and interactions with auxins and ACC regulation of
      ethylene in canola (Brassica campestris).
AB  - The possible interaction of the plant hormones auxin and ethylene and the role of
      1-aminocyclopropane-1-carboxylate (ACC) deaminase containing bacteria on ethylene
      production in canola (Brassica campestris) in the presence of inhibitory
      concentrations of growth regulators were investigated. The effects of auxin
      (indole-3-acetic acid and 2,4-dichlorophenoxy acetic acid), auxin transport
      inhibitor 2-(p-chlorophenoxy)-2-methylpropionic acid, ethylene precursor 1
      aminocyclopropane-1-carboxylate and ethylene synthesis inhibitor L-alpha-(2
      aminoethoxyvinyl)glycine hydrochloride on root elongation were concentration
      dependent. Exogenous addition of growth regulators influences the enzyme
      activities of ethylene production and we have presented here evidences that
      support the hypothesis that inhibitory effects of auxin on root elongation are
      independent of ethylene. Additionally, we have proved that inoculation of ACC
      deaminase containing Methylobacterium oryzae sequester ACC exuded from roots and
      hydrolyze them lowering the concentration of ACC in root exudates. However, the
      inhibitory actions of exogenous additions of auxins could not be ameliorated by
      bacterial inoculation that reduces ethylene concentration in canola seedlings.

PMID- 17541631
TI  - Cloning and functional characterization of PpDBF1 gene encoding a DRE-binding
      transcription factor from Physcomitrella patens.
AB  - The dehydration-responsive element binding (DREB) transcription factors play
      central roles in regulating expression of stress-inducible genes under abiotic
      stresses. In the present work, PpDBF1 (Physcomitrella patens DRE-binding Factor1)
      containing a conserved AP2/ERF domain was isolated from the moss P. patens.
      Sequence comparison and phylogenetic analysis revealed that PpDBF1 belongs to the
      A-5 group of DREB transcription factor subfamily. The transcriptional activation
      activity and DNA-binding specificity of PpDBF1 were verified by yeast one-hybrid
      and electrophoretic mobility shift assay experiments, and its nuclear
      localization was demonstrated by particle biolisitics. PpDBF1 transcripts were
      accumulated under various abiotic stresses and phytohormones treatments in P.
      patens, and transgenic tobacco plants over-expressing PpDBF1 gained higher
      tolerance to salt, drought and cold stresses. These results suggest that PpDBF1
      may play a role in P. patens as a DREB transcription factor, implying that
      similar regulating systems are conserved in moss and higher plants.

PMID- 17541632
TI  - Identification and fine mapping of a thermo-sensitive chlorophyll deficient
      mutant in rice (Oryza sativa L.).
AB  - A thermo-sensitive chlorophyll deficient mutant was isolated from more than
      15,000 transgenic rice lines. The mutant displayed normal phenotype at 23 degrees
      C or lower temperature (permissive temperature). However, when grown at 26
      degrees C or higher (nonpermissive temperature) the plant exhibited an abnormal
      phenotype characterized by yellow green leaves. Genetic analysis revealed that a
      single nuclear-encoded recessive gene is responsible for the mutation, which is
      tentatively designed as cde1(t) (chlorophyll deficient 1, temporally). PCR
      analysis and hygromycin resistance assay indicated the mutation was not caused by
      T-DNA insertion. To isolate the cde1(t) gene, a map-based cloning strategy was
      employed and 15 new markers (five SSR and ten InDels markers) were developed. A
      high-resolution physical map of the chromosomal region around the cde1(t) gene
      was made using F(2) and F(3) population consisting of 1,858 mutant individuals.
      Finally, the cde1(t) gene was mapped in 7.5 kb region between marker ID10 and
      marker ID11 on chromosome 2. Sequence analysis revealed only one candidate gene,
      OsGluRS, in the 7.5 kb region. Cloning and sequencing of the target region from
      the cde1(t) mutant showed that a missense mutation occurred in the mutant. So the
      OsGluRS gene (TIGR locus Os02 g02860) which encode glutamyl-tRNA synthetase was
      identified as the Cde1(t) gene.

PMID- 17541634
TI  - Hepatic hematoma in a neonate with a high level of alpha-fetoprotein.
AB  - Hepatic hematomas in neonates are uncommon lesions. When they are large or
      subcapsular in location, they can rupture with clinical signs of hemoperitoneum.
      We report a case of subcapsular hepatic hematoma (SHH) associated with a high
      level of alpha-fetoprotein (AFP), for which diagnosis was made with conservative
      management, following up with the reduction in size at ultrasound examination and
      the reduction of the level of AFP.

PMID- 17541633
TI  - The threat of avian influenza A (H5N1). Part IV: Development of vaccines.
AB  - Among emerging and re-emerging infectious diseases, influenza constitutes one of
      the major threats to mankind. In this review series epidemiologic, virologic and
      pathologic concerns raised by infections of humans with avian influenza virus
      A/H5N1 are discussed. This fourth part focuses on vaccine development. Several
      phase I clinical studies with vaccines against H5 viruses have demonstrated
      limited efficacy compared to seasonal influenza vaccines. To induce protective
      immunity two immunisations with increased amounts of H5N1 vaccine were required.
      Novel vaccination strategies that are egg- and adjuvant-independent, broadly
      cross-reactive and long-lasting are highly desirable.

PMID- 17541635
TI  - Central precocious puberty due to hypothalamic hamartoma in a 7-month-old infant
      girl.
AB  - Hypothalamic hamartomas (HH) are rare congenital lesions of the tuber cinereum
      presenting with the classic triad of gelastic epilepsy, central precocious
      puberty (CPP) and developmental delay. In light of the important and diverse
      consequences of precocious puberty for affected children and their families, a
      correct diagnosis without delay is imperative. We present here a rare case of a 7
      month-old infant girl with CPP and HH who was successfully treated with depot
      gonadotropin-releasing hormone (GnRH) analogue is presented.

PMID- 17541636
TI  - WT1 gene mutations in three girls with nephrotic syndrome.
AB  - Denys-Drash syndrome and Frasier syndrome are two related conditions caused by
      mutations of the Wilms tumor gene, WT1. Both syndromes are characterized by male
      pseudohermaphrodism, a progressive glomerulopathy, and the development of
      genitourinary tumors. This study examines three girls with steroid-resistant
      nephrotic syndrome related to mutations in the WT1 gene, but with normal 46, XX
      karyotype and normal female phenotype. WT1 mutation analysis should be routinely
      done in females with steroid-resistant nephrotic syndrome.

PMID- 17541637
TI  - Distortion product otoacoustic emissions at 6 months in term infants after
      perinatal hypoxia-ischaemia or with a low Apgar score.
AB  - Distortion product otoacoustic emissions (DPOAEs) were analyzed at 6 months of
      age in term infants who had perinatal hypoxia-ischaemia (HI) and those who had a
      low Agar score alone to detect any abnormalities in cochlear function and any
      difference between the two groups of infants. The f2 primary tone was presented
      at ten frequencies (0.5-10 kHz). Both the left and right ears were tested.
      Compared to normal term controls, both the infants after perinatal HI and those
      with a low Apgar score alone showed lower DPOAE pass rates, mainly at 1-4 kHz at
      which the pass rates were decreased significantly (P < 0.05-0.01). The general
      pattern of DPOAE pass rates at different frequencies was similar in the two
      groups of infants. The pass rates at 1, 5 and 6 kHz tended to be lower in the
      infants after perinatal HI than those with a low Apgar score alone, although not
      statistically significant. Conclusions At 6 months of age, infants after
      perinatal HI or with a low Apgar score alone had a relatively poor cochlear
      function, mainly at 1-4 kHz. There are no major differences between the two
      groups of infants.

PMID- 17541638
TI  - Respiratory syncytial virus infection in infants admitted to paediatric intensive
      care units in London, and in their families.
AB  - We carried out a study in five London paediatric intensive care units (PICUs),
      with the objectives of describing a cohort of infants with respiratory syncytial
      virus (RSV) infection, comparing hospital diagnosis with PCR results and
      investigating the spread of RSV in families. Eligible infants were under 5 months
      old and admitted betweem November 1998 and October 1999 with respiratory failure,
      apnoea and/or bradycardia or acute life threatening episodes (ALTE). We diagnosed
      RSV by PCR analysis of nasopharyngeal aspirate, and in contacts by PCR of
      pernasal swabs. Of the 137 eligible infants, 66% (91/137) were recruited; of
      these, 82% (75/91) had RSV, with 47% (35/75) diagnosed by hospital laboratory
      tests and 93% (70/75) by PCR. The median duration of ventilation was 4.4 days,
      the length of stay on PICU, 8.6 days, and the length of stay in hospital, 15.9
      days. In most families (62%), the parents and siblings developed symptoms of RSV
      infection at the same time as the infant. When the index infant was a secondary
      case, primary cases occurred in both older siblings (16 families) and adults (11
      families). Silent RSV infection occurred frequently amongst children and adults.
      RSV is under-diagnosed in PICUs. PCR increases the rate of diagnosis of RSV
      compared to routine hospital diagnostic methods. Young infants are most often
      infected at the same time as or before their parents and siblings, indicating
      that the source may be outside the household; vaccinating family members may not
      prevent RSV infection in infants.

PMID- 17541639
TI  - Immunogenicity and safety of a tetravalent measles-mumps-rubella-varicella
      vaccine co-administered with a booster dose of a combined diphtheria-tetanus
      acellular pertussis-hepatitis B-inactivated poliovirus-Haemophilus influenzae
      type b conjugate vaccine in healthy children aged 12-23 months.
AB  - This study was undertaken to assess the co-administration of an experimental
      measles-mumps-rubella-varicella vaccine (MMRV, GlaxoSmithKline Biologicals) with
      a combined diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated
      poliovirus-Haemophilus influenzae type b conjugate (DTPa-HBV-IPV/Hib) vaccine in
      healthy children. Healthy children aged 12-23 months (N = 451) were randomised to
      one of three parallel groups to receive one dose of MMRV vaccine co-administered
      with a booster dose of DTPa-HBV-IPV/Hib vaccine (co-administration group), or one
      dose of MMRV vaccine alone (MMRV group), or a booster dose of DTPa-HBV-IPV/Hib
      vaccine alone (DTPa-HBV-IPV/Hib group). No differences in seroconversion rates
      for measles (>95%), mumps (>80%), rubella (>99%) and varicella (>98%) were seen
      between the co-administration group and the MMRV group. No differences in
      geometric mean titres (GMTs) were observed between the two groups with the
      exception of anti-measles titres, which were observed to be higher in the MMRV
      group than in the co-administration group (4,419.2 vs. 3,441.8 mIU/ml
      respectively). Immune response to the booster dose of DTPa-HBV-IPV/Hib vaccine
      was observed to be similar in the co-administration group and the DTPa-HBV
      IPV/Hib group. Co-administration of the MMRV vaccine with a booster dose of DTPa
      HBV-IPV/Hib vaccine was well-tolerated and did not exacerbate the reactogenicity
      profile of either vaccine. In summary, GlaxoSmithKline Biologicals' experimental
      MMRV vaccine was immunogenic and well-tolerated when administered with a booster
      dose of DTPa-HBV-IPV/Hib vaccine during the second year of life. The ability to
      co-administer the MMRV vaccine at the same time as other routine childhood
      immunisation vaccines could increase compliance with varicella vaccination in
      countries where this vaccine is already recommended and may facilitate
      implementation of varicella vaccination elsewhere.

PMID- 17541640
TI  - Prolonged follow up of seven patients affected by hepatosplenic granulomata due
      to cat-scratch disease.
AB  - This study is a retrospective analysis of seven patients with hypoechogenic
      lesions in the liver and/or spleen due to Bartonella henselae, who were followed
      from 1998 through to 2005 by the Department of Pediatrics, Turin University. In
      addition to showing constitutional symptoms, four children had skin lesions
      suggestive of injuries inflicted by cats, and one child had a history of exposure
      to cats. The origin of the infection remained undefined in the other two
      patients. Humoral tests enabled a precise diagnosis in all children. Treatment
      with macrolides or combinations of two active antibiotics for at least 2-3 weeks
      led to the definitive clearance of infection, although residual intraparenchymal
      lesions persisted in five patients for several months or years. Conclusion B.
      henselae serology allows an easy diagnosis of multiple hepatosplenic granulomata,
      a clinical picture that appears to be under-recognized. Macrolides or a
      combination of two active antibiotics for 2-3 weeks leads to a rapid clinical
      response and a definitive clearance of infection.

PMID- 17541641
TI  - A new species of Syphacia (Nematoda: Oxyuridae) from Oligoryzomys nigripes
      (Rodentia: Cricetidae) in Argentina.
AB  - The aim of this paper is to describe Syphacia kinsellai n. sp. (Nematoda:
      Oxyuridae) from the cecum of Oligoryzomys nigripes (Olfers 1818) (Sigmodontinae:
      Oryzomyini) captured in Misiones Province, Argentina. The new species can be
      differentiated from other species of the genus principally by the shape of the
      cephalic plate; distribution of submedian papillae and amphids; development of
      porous badge; presence of derids in females; absence of cervical and lateral
      alae; shape and structure of accessory hook of gubernaculum; and distance of
      excretory pore and vulva from the anterior extremity. Until the present, only two
      species of Syphacia had been reported from Argentina in sigmodontine rodents, the
      first one parasitizes an Oryzomyini host and the second one an Akodontini host.
      This new species is the second record of Syphacia from the tribe Oryzomyini in
      Argentina; however, we propose that the first record, S. oryzomae, should be
      treated as a nomen dubium.

PMID- 17541642
TI  - High-density single nucleotide polymorphism array analysis in patients with
      germline deletions of 22q11.2 and malignant rhabdoid tumor.
AB  - Malignant rhabdoid tumors are highly aggressive neoplasms found primarily in
      infants and young children. The majority of rhabdoid tumors arise as a result of
      homozygous inactivating deletions or mutations of the INI1 gene located in
      chromosome band 22q11.2. Germline mutations of INI1 predispose to the development
      of rhabdoid tumors of the brain, kidney and extra-renal tissues, consistent with
      its function as a tumor suppressor gene. We now describe five patients with
      germline deletions in chromosome band 22q11.2 that included the INI1 gene locus,
      leading to the development of rhabdoid tumors. Two patients had phenotypic
      findings that were suggestive but not diagnostic for DiGeorge/Velocardiofacial
      syndrome (DGS/VCFS). The other three infants had highly aggressive disease with
      multiple tumors at the time of presentation. The extent of the deletions was
      determined by fluorescence in situ hybridization and high-density oligonucleotide
      based single nucleotide polymorphism arrays. The deletions in the two patients
      with features of DGS/VCFS were distal to the region typically deleted in patients
      with this genetic disorder. The three infants with multiple primary tumors had
      smaller but overlapping deletions, primarily involving INI1. The data suggest
      that the mechanisms underlying the deletions in these patients may be similar to
      those that lead to DGS/VCFS, as they also appear to be mediated by related, low
      copy repeats (LCRs) in 22q11.2. These are the first reported cases in which an
      association has been established between recurrent, interstitial deletions
      mediated by LCRs in 22q11.2 and a predisposition to cancer.

PMID- 17541643
TI  - Immunohistological markers for staging neurogenesis in adult hippocampus.
AB  - Neurogenesis in the adult dentate gyrus (DG) of the hippocampus occurs
      constitutively throughout postnatal life, and the rate of neurogenesis within the
      DG can be altered under various physiological and pathophysiological conditions.
      Adult neurogenesis includes the process in which the division of a precursor cell
      takes place and the multi-step process (proliferation, differentiation,
      migration, targeting, and synaptic integration) that ends with the formation of a
      postmitotic functionally integrated new neuron. During specific time-frames of
      adult neurogenesis, various markers are expressed that correlate with the
      differentiation steps along the pathway from early progenitor cells to newly
      generated postmitotic neurons within the DG. Markers that are currently widely
      used for the investigation of adult hippocampal neurogenesis are: glial
      fibrillary acidic protein, nestin, Pax6, NeuroD, PSA-NCAM, doublecortin, TUC-4,
      Tuj-1, and calretinin. The discovery and development of specific markers that
      allow the time-course and fate of neurons to be followed during adult
      neurogenesis in a detailed and precise fashion are not only helpful for gaining
      further insights into the genesis of new neurons in the hippocampus, but also
      might be applicable to the development of strategies for therapeutic
      interventions.

PMID- 17541644
TI  - An experimental study of the effects of weed invasion on lizard phenotypes.
AB  - We examined how a weed affected the basking and activity of a diurnal lizard, and
      the potential cascading effects of these shifts for life history strategies and
      expression of morphology. Hatchlings of the diurnal lizard Lampropholis delicata
      were raised to maturity in outdoor enclosures that mimicked high, moderate and
      low invasion by a sprawling plant (blue periwinkle, Vinca major). Skinks depend
      on sunlight for growth and maintenance. Periwinkle differs from displaced
      grassland by being structurally complex and blocking sunlight. Lizards restricted
      to the enclosure floor achieved preferred body temperatures only when exposure to
      periwinkle was moderate or low. However, lizards in high invasion enclosures
      could reach preferred body temperatures by climbing plants and basking on exposed
      canopy. This shift in basking strategy resulted in lizards growing longer hind
      limbs compared with animals that rarely (moderate invasion) and never (low
      invasion) climbed plants. Consequently, lizards reared in high invasion
      enclosures sprinted faster than conspecifics reared in lower invasion
      environments. Throughout the study there was no significant variation among
      treatments in the tendency of animals to be moving when they were not hidden.
      However, lizards in high invasion treatments hid more often during the day, were
      lighter in body mass, and females had lighter clutch masses and offspring than
      did those from moderate and low invasion enclosures. Thus, microhabitat
      degradation can drive a cascade of changes to an animal's ecology.

PMID- 17541645
TI  - Scale-specific correlations between habitat heterogeneity and soil fauna
      diversity along a landscape structure gradient.
AB  - Habitat heterogeneity contributes to the maintenance of diversity, but the extent
      that landscape-scale rather than local-scale heterogeneity influences the
      diversity of soil invertebrates-species with small range sizes-is less clear.
      Using a Scottish habitat heterogeneity gradient we correlated Collembola and
      lumbricid worm species richness and abundance with different elements (forest
      cover, habitat richness and patchiness) and qualities (plant species richness,
      soil variables) of habitat heterogeneity, at landscape (1 km(2)) and local (up to
      200 m(2)) scales. Soil fauna assemblages showed considerable turnover in species
      composition along this habitat heterogeneity gradient. Soil fauna species
      richness and turnover was greatest in landscapes that were a mosaic of habitats.
      Soil fauna diversity was hump-shaped along a gradient of forest cover, peaking
      where there was a mixture of forest and open habitats in the landscape. Landscape
      scale habitat richness was positively correlated with lumbricid diversity, while
      Collembola and lumbricid abundances were negatively and positively related to
      landscape spatial patchiness. Furthermore, soil fauna diversity was positively
      correlated with plant diversity, which in turn peaked in the sites that were a
      mosaic of forest and open habitat patches. There was less evidence that local
      scale habitat variables (habitat richness, tree cover, plant species richness,
      litter cover, soil pH, depth of organic horizon) affected soil fauna diversity:
      Collembola diversity was independent of all these measures, while lumbricid
      diversity positively and negatively correlated with vascular plant species
      richness and tree canopy density. Landscape-scale habitat heterogeneity affects
      soil diversity regardless of taxon, while the influence of habitat heterogeneity
      at local scales is dependent on taxon identity, and hence ecological traits, e.g.
      body size. Landscape-scale habitat heterogeneity by providing different niches
      and refuges, together with passive dispersal and population patch dynamics,
      positively contributes to soil faunal diversity.

PMID- 17541646
TI  - Divergent compensatory growth responses within species: linked to contrasting
      migrations in salmon?
AB  - Animals often exhibit accelerated or "compensatory" growth (CG) after periods of
      environmentally induced growth depression, raising important questions about how
      they cope with environmental variability. We tested an underexplored hypothesis
      regarding the evolutionary consequences of CG; namely, that natural populations
      differ in CG responses. Common-garden experiments were used to compare subadult
      growth following food restriction between groups (control, treatment) of two
      Atlantic salmon (Salmo salar) populations and their first-generation (F(1))
      hybrids. The populations are found at similar latitudes but characterized by
      differences in migration distance. We predicted that long-distance migrants would
      better maintain growth trajectories following food restriction than short
      distance migrants because they: (1) require larger body sizes to offset energetic
      costs of migration and (2) face greater time constraints for growth as they must
      leave non-breeding areas earlier to return to breeding areas. Long-distance
      migrants grew faster, achieved quicker CG (relative to controls), and their
      overall body morphology was more streamlined (a trait known to improve swimming
      efficiency) than slower growing short-distance migrants. F(1) hybrids were
      generally intermediate in "normal" growth, CG, and body morphology. We concluded
      that CG responses may differ considerably among populations and that the
      conditions generating them are likely interconnected with selection on a suite of
      other traits.

PMID- 17541647
TI  - A clinico-genetic study of renal coloboma syndrome in children.
AB  - Renal coloboma syndrome (RCS) is an autosomal dominant disorder caused by PAX2
      gene mutations and characterized by renal hypoplasia and optic disc coloboma. The
      clinical findings were retrospectively reviewed, and all coding regions of the
      PAX2 gene were sequenced, in six children with RCS. A c.619_620insG mutation was
      detected in five patients, including two siblings, and a novel p.Arg104X mutation
      was detected in one patient. All the patients had progressive renal dysfunction
      and bilateral hypoplastic kidneys without vesicoureteral reflux (VUR), but the
      rate of progression to end-stage renal disease showed some diversity. The ocular
      manifestations showed wide variability, ranging from subtle optic disc anomalies
      to microphthalmia. In one family with two affected siblings, maternal germline
      mosaicism was suggested by an intragenic microsatellite marker study. In
      conclusion, there are variable renal and ocular manifestations in RCS without
      significant phenotype-genotype correlations. VUR is not a cardinal renal
      manifestation of RCS. The possibility of germline mosaicism should be considered
      during molecular diagnosis and genetic counseling for PAX2 mutations.

PMID- 17541648
TI  - Idiopathic hypercalciuria associated with urinary tract infection in children.
AB  - The aim of this study was to evaluate the association between idiopathic
      hypercalciuria (IH) and urinary tract infection (UTI) in children. This
      prospective clinical study included 75 patients with UTI (without urinary tract
      malformations and lithiasis) and a control group of 30 healthy children. Of the
      total number of patients with UTI, 21% (n = 16/75) had IH, but only 7% (n = 2/30)
      with IH were reported in the control group (p < 0.05). Recurrent UTI affected 33%
      (n = 25/75) of patients , and in 67% (n = 50/75) of patients, UTI was diagnosed
      for the first time. In the group of patients with recurrent UTI, 44% (n = 11/25)
      had IH, but only 10% (n = 5/50) were reported in the group of patients with first
      time UTI (p < 0.05). The results of multifactorial logistic regression analysis
      showed that clinical and laboratory parameters (recurrent UTI, dysuria, and
      microscopic hematuria) may predict the diagnosis of IH in 80% of patients and
      absence of IH in 87% of cases. In our opinion, IH is a major contributing factor
      to UTI, especially to recurrent UTI in children.

PMID- 17541649
TI  - Does feeding in infancy effect the development of IgA nephropathy?
AB  - Gut permeability to antigens is immature at birth, and while early administration
      of antigenic foods delays its maturation, breast-feeding accelerates it. We aimed
      to evaluate whether exposure to antigenic foods in early life is associated with
      a predisposition for immunoglobulin A nephropathy (IgAN). Three groups of
      children with IgAN (group 1), non-IgA glomerulopathies (group 2), and healthy
      controls (group 3) were formed. Parents filled out a questionnaire regarding
      gestational and postnatal ages, birth weight, and feeding by breast milk,
      formula, cow's milk, and complementary foods. All groups were similar for age,
      gender, birth weight, rate and duration of breast-feeding, and rate of formula
      feeding. Cow's milk consumption rate was higher in groups 1 and 2 than in group
      3. Whereas introduction of formula was earlier in groups 1 and 2 than in group 3,
      feeding by cow's milk and weaning were earlier in group 1 than in the other
      groups. The respective best cutoff ages were 3.5 [odds ratio (OR) 28)], 3.75 (OR
      5.7), and 5.5 (OR 10.5) months for formula, cow's milk, and complementary foods,
      respectively, for predicting the presence of IgAN. The results of this
      preliminary study indicate that early introduction of antigenic foods might
      increase the risk of future primary IgAN.

PMID- 17541651
TI  - [Pain and consciousness. Articles from the summer workshop held by the German
      Interdisciplinary Collaboration for Pain Therapy (DIVS) in 2005].
AB  - Six articles are presented which illustrate the activities at the summer workshop
      "Pain and awareness" held 27-28 May 2005 in Marienfeld by the German
      Interdisciplinary Collaboration for Pain Therapy (DIVS). One article on pain
      constructs in the mind explains the advantages of functional imaging methods:
      these enable characterization of partial aspects of pain processing in the brain
      and the mechanisms that lead to chronic states of pain syndromes. A further
      overview explains the influence of different drugs on pain perception and various
      conscious states. How back pain patients experience their illness was analyzed in
      a study using an explanatory model interview: somatic aspects were dominant, but
      in three-fourths of the patients psychological illness attributions also played a
      role. A summary from the perspective of religious history and theology explores
      how pain is interpreted and accepted in various religious communities. Another
      article addresses hypnosis as a complementary technique to anesthesia procedures
      in surgical medicine, for treating chronic pain and experimental acute pain. The
      last contribution deals with how people in different cultures experience pain:
      ethnocentric bias can lead to difficulties in communication and misjudgments when
      treating foreign-born patients. All in all the workshop highlighted important
      formative factors in pain processing in a condensed form and offered stimulating
      perspectives for this area of pain research and future treatment options.

PMID- 17541652
TI  - Drug combinations with the potential to interact among cancer patients.

PMID- 17541653
TI  - An extended maintenance dosing regimen of epoetin alfa 80,000 U every 3 weeks in
      anemic patients with cancer receiving chemotherapy.
AB  - BACKGROUND: The purpose of this study was to evaluate the safety and efficacy of
      epoetin alfa (EPO) at an initial dose of 60,000 Units (U) once weekly (QW)
      followed by extended dosing of 80,000 U every 3 weeks (Q3W) in patients with
      chemotherapy-induced anemia (CIA). MATERIALS AND METHODS: Anemic patients
      (hemoglobin [Hb] < or = 11 g/dl) receiving Q3W chemotherapy for nonmyeloid
      malignancy were enrolled in this prospective, open-label, single-arm study to
      receive EPO 60,000 U subcutaneously (SC) QW (initial dosing phase [IDP]) until a
      target Hb level of 12 g/dl was reached (maximum 12 weeks). Patients who achieved
      an Hb level of 12 g/dl at any point during the IDP then entered the extended
      dosing phase (EDP; EPO 80,000 U SC Q3W). Maximum study duration (IDP + EDP) was
      24 weeks. The primary endpoint was the proportion of patients achieving a
      hematopoietic response (Hb increase > or = 2 g/dl from baseline or Hb > or = 12
      g/dl) during the IDP. RESULTS: One hundred fifteen patients were enrolled. During
      the IDP, 76% (84/110) of patients achieved a hematopoietic response, and 15%
      (17/115) received red blood cell (RBC) transfusion. Sixty-three percent (73/115)
      of patients entered the EDP, and 88% (64/73) of these patients maintained a mean
      Hb level > 11.0 and < or =13.0 g/dl. Two of 73 patients received RBC transfusion
      during the EDP. Adverse events were consistent with the underlying disease and
      chemotherapy treatment. CONCLUSION: These results suggest that initiation of EPO
      60,000 U SC QW is effective in the treatment of CIA and that EPO 80,000 U SC Q3W
      can be an effective extended dosing option.

PMID- 17541654
TI  - High isolation rate of adenovirus serotype 7 from South Korean military recruits
      with mild acute respiratory disease.
AB  - Adenovirus is a major cause of acute respiratory disease (ARD) in military
      recruits. When South Korean military recruits with ARD were surveyed, adenovirus
      was identified in 122 (61.0%) of the 200 recruits studied. Moreover, all cases of
      ARD involving adenovirus were caused by serotype 7.

PMID- 17541655
TI  - Epidemiology and outcome of primary community-acquired bacteremia in adult
      patients.
AB  - We conducted this study to determine the associated factors and outcomes of
      community-acquired primary bacteremia (PB), to describe the most frequently
      isolated microorganisms, the antibiotic resistance pattern, and to guide the most
      appropriate antibiotic treatment. A total of 1,640 community-acquired bacteremia
      cases in nonneutropenic adults were consecutively enrolled from January 2003 to
      May 2006 and prospectively followed up. Nonconditional logistic regression
      methods were used with PB and death as dependent variables. Secondary bacteremia
      (SB) was present in 1,440 patients, and 200 (12%) cases were PB. The independent
      factors associated with PB were male sex (OR 1.69, 95%CI 1.27-2.25, P = 0.001)
      and an ultimately or rapidly fatal prognosis for an underlying disease (OR 2.48,
      95%CI 1.84-3.34, P = 0.001). The most frequently isolated microorganisms in PB
      were E. coli and other enterobacteria (26 and 22%, respectively) and S. aureus
      (15%). There were 28 and 37% ciprofloxacin-resistant E. coli strains in SB and
      PB, respectively (P = 0.2). Mortality was significantly higher in PB cases (13 vs
      8%, P = 0.04). The independent factors associated with mortality in PB were
      ultimately or rapidly fatal prognosis of underlying disease (OR 2.1, 95%CI 1.41
      3.13, P = 0.001), lack of fever at the moment of bacteremia (OR 2.38, 95%CI 1.18
      4.76, P = 0.02) and incorrect empirical antibiotic therapy (OR 2.01, 95%CI 1.22
      3.33, P = 0.006). The initial empiric antibiotic treatment was more frequently
      incorrect in PB than in SB, and this was a predictive factor for mortality in PB.
      The resistance pattern of E. coli, other enterobacteria and S. aureus in every
      setting should guide the most appropriate empirical treatment for PB.

PMID- 17541656
TI  - Evaluation of the IDI-MRSA assay on the SmartCycler real-time PCR platform for
      rapid detection of MRSA from screening specimens.
AB  - Rapid accurate detection is a prerequisite for the successful control of
      meticillin-resistant Staphylococcus aureus (MRSA). The IDI-MRSA real-time
      polymerase chain reaction (PCR) assay was designed to provide rapid results from
      nasal specimens collected in Stuart's liquid transport medium. This study has
      evaluated the IDI-MRSA kit for use in a clinical laboratory by investigating the
      following parameters: (1) limits of detection (LoD), (2) performance with Amies'
      gel-based transport medium, (3) ability to detect strains of MRSA in a collection
      representative of MRSA in Ireland since 1974 (n=113) and (4) performance in a
      clinical trial with swabs from nose, throat and groin/perineum sites from 202
      patients. LoDs (colony-forming units per ml) of the IDI-MRSA kit, direct culture
      on MRSA-Select chromogenic agar (CA) and salt-enrichment culture (with subculture
      onto CA) were 10(3), 10(3) and 10(2), respectively. LoDs with Stuart's and Amies'
      transport media were comparable. All except one of the 113 MRSA isolates were
      detected by the kit but, when six control strains carrying staphylococcal
      cassette chromosome mec (SCCmec) type IV element subtypes IVa-d and SCCmec types
      V and V(T) were tested, the kit failed to detect MRSA carrying SCCmec V. The
      sensitivity and specificity for detection of MRSA from nose, throat and
      groin/perineum specimens were comparable with slightly lower sensitivities from
      throat and groin/perineum specimens compared with nasal swabs (90%, 97%; 89%,
      99%; 88%, 99%, respectively). Overall sensitivity, specificity and positive and
      negative predictive values for specimens from all sites were 88%, 99%, 94% and
      97%, respectively. Further developments to improve the sensitivity of this highly
      worthwhile assay are required.

PMID- 17541657
TI  - Diabetic muscle infarction: a rare complication of advanced diabetes mellitus.
AB  - Diabetic muscle infarction is a rare complication of diabetes mellitus first
      described in 1965. It typically arises in patients with long-standing diabetes
      mellitus who have complications of the disease, including nephropathy,
      retinopathy, and neuropathy. It typically presents with acute onset of thigh pain
      with an associated palpable tender mass. Recurrent episodes in the same or
      opposite limb are common. Laboratory evaluation does not generally show any
      consistent abnormality except for poor glucose control. Histologic features of
      diabetic muscle infarction consist of large areas of muscle necrosis and edema.
      Magnetic resonance imaging (MRI) findings in patients without clinical evidence
      of infection may be typical enough to make tissue biopsy unnecessary. In the
      appropriate clinical setting, MRI may obviate invasive testing and is the
      preferred imaging modality. Treatment is supportive with analgesics, rest, and
      immobilization.

PMID- 17541658
TI  - Fatal methadone intoxication in a child.
AB  - Methadone is an opiate used as part of the treatment for heroin abuse; it can be
      ingested orally. We present the lethal outcome of a 22-month-old child
      intoxicated after methadone ingestion.

PMID- 17541659
TI  - Acute calcific periarthritis of the hand and wrist: a series and review of the
      literature.
AB  - This article presents three patients with acute calcific periarthritis (ACP) of
      the hand and wrist. ACP is an unusual, painful, monoarticular, periarticular
      inflammatory process associated with juxtaarticular deposits of amorphous calcium
      hydroxyapatite. ACP is a distinct clinical subset of hydroxyapatite deposition
      disease. ACP has a high rate of misdiagnosis because of its rare occurrence and
      its clinical resemblance to other entities. Clinical presentation may simulate
      infection, and the associated periarticular calcifications may be mistaken for
      gout, pseudogout, or other entities. One third of patients with ACP provide a
      history of antecedent trauma. Treatment is conservative. Patients typically will
      have a reduction in symptoms within 4-7 days after the acute onset of pain.
      Radiographically, the periarticular mineralization usually resolves or markedly
      decreases within 2-3 weeks, although on occasion, some calcifications may remain
      visible for months. Failure to recognize and correlate the typical clinical and
      radiographic presentation of this disease may lead to unnecessary diagnostic
      tests, invasive procedures, and inappropriate medication.

PMID- 17541660
TI  - Resolution of gallstone ileus with spontaneous evacuation of gallstone.
AB  - Gallstone ileus (GSI) is a rare cause of small bowel obstruction (SBO). Even more
      extraordinary is the spontaneous evacuation of a gallstone, which has caused SBO.
      A 69-year-old gentleman presented with symptoms and signs of SBO. His plain
      abdominal X-ray revealed dilated loops of the small bowel and opacity in the
      region of the terminal ileum consistent with a diagnosis of GSI. Because of
      severe cardiorespiratory co-morbidities, the patient was treated conservatively
      and improved within 24 h. A CT scan revealed that the stone had passed into the
      rectum and was spontaneously evacuated. If the gallstone is <2.5 cm on CT scan,
      spontaneous evacuation is a real possibility and initial conservative treatment
      in a high-risk surgical patient is a consideration.

PMID- 17541661
TI  - Sonographic measurement of the inferior vena cava as a predictor of shock in
      trauma patients.
AB  - Detecting and monitoring blood loss is always a challenging dilemma in emergency
      settings. The diameter of the inferior vena cava (IVC) in trauma patients may be
      useful in this way. This has been classically done with computed tomography (CT);
      however, doing it with ultrasound as a bedside easily available modality is a
      relatively novel approach. Between January 2006 and March 2006, 88 injured
      patients referred to our center were investigated. The patients were divided in
      to two groups: a shock group (n = 11, 12.5%) and a control group (n = 77, 87.5%)
      who were trauma patients with normal blood pressure. The maximum anteroposteroir
      diameter of IVC was measured ultrasonographically both in inspiration (i) and
      expiration (e) by M-mode in the subxyphoid area. The difference between the
      diameters of IVCe and IVCi was regarded as collapsibility, and collapsibility
      index was defined as IVCe - IVCi/IVCe. Statistical analysis included Mann-Whitney
      U test and correlation analysis. The average diameters of IVCe and IVCi in the
      shock group at arrival were significantly smaller than in the control group (5.6
      +/- 0.8 mm, 4.0 +/- 0.7 mm versus 11.9 +/- 2.2 mm, 9.6 +/- 2.0 mm; P < 0.0001).
      The maximum diameter of IVC in the shock group was in a 30-year-old male patient
      with an IVCe and IVCi of 7.0 and 5.3 mm, respectively. Correlation analysis
      revealed a negative correlation between the diameter of IVCe (r = 0.72) and IVCi
      (r = 0.73) and the presence of shock. Regarding the collapsibility index, the
      mean collapsibility index of IVC was significantly higher in the shock group
      compared to patients in the control group (27% versus 20%; P < 0.001). The
      diameter of IVC was found to correlate with shock in trauma patients. The
      measurement of the IVC may be an important addition to the ultrasonographic
      evaluation of trauma and other potentially volume-depleted patients and can be
      added to the focused assessment with sonography for trauma (FAST) of the trauma
      patient with minimum additional time.

PMID- 17541662
TI  - Within-session reproducibility of motion-onset VEPs: effect of
      adaptation/habituation or fatigue on N2 peak amplitude and latency.
AB  - We explored the effect of repeated visual stimulation on motion-onset visual
      evoked potentials (M-VEPs) during 25 min recording sessions in 10 subjects. The
      aim of the experiment was to determine influence of global motion adaptation
      (without motion-aftereffect) on intra-individual variability of M-VEPs and to
      suggest an optimal recording design for clinical examination. In addition to well
      described middle-time sensory adaptation, we also observed a long-time effect on
      motion specific N2 peak (155 ms). The N2 peak exhibited a strong relationship
      between its latency and inter-peak amplitude to the duration of recording in
      occipito-parietal derivations. In addition to the middle-term adaptation, N2 peak
      latency was prolonged by 10 ms and amplitude was attenuated by 30% with respect
      to the start of the experiment. An exponential model was employed to describe the
      dependency. The model can be used to reduce intra-individual variability during
      examination. Observed resemblance between the measured electrophysiological
      values and already published metabolic changes (glucose and oxygen utilization)
      during brain processing of visual information is discussed.

PMID- 17541663
TI  - Practice patterns of screening for sleep apnea in physicians treating PCOS
      patients.
AB  - Women with polycystic ovarian syndrome (PCOS) have been shown to have a very high
      prevalence of obstructive sleep apnea (OSA). Screening for OSA is recommended for
      PCOS patients. How far this is carried out in actual practice is unknown. To
      study practice patterns with regard to screening for OSA in physicians-both
      obstetrician/gynecologists (ObGyn) and endocrinologist-who manage PCOS. A
      secondary aim of this study was to identify practice differences, if any. Two
      hundred ObGyn and 140 endocrine academic institutions were contacted and mailed
      with questionnaires, if willing to participate. Responses were obtained from 50
      (29.4%) ObGyn physicians and 29 (26.4%) endocrine physicians. The questionnaire
      was closed-ended. Physicians reported a high occurrence of obesity-36.7% of the
      physicians reported that 75-100% of their patients had morbid obesity. However,
      reported prevalence of symptoms was low-86.1% of the physicians felt their
      patients snored infrequently (<25% of the time) and 74.7% felt that their
      patients had excess daytime sleepiness (EDS) infrequently. Of the physicians,
      92.4% ordered a sleep study <25% of the time. No significant difference in
      practice between the specialties was identified. Physicians who manage PCOS
      patients do not believe that these patients have significant symptoms nor warrant
      frequent testing for OSA. This may reflect lack of knowledge about the link or
      may imply that PCOS patients remain largely asymptomatic. Educating specialist
      physicians managing PCOS about OSA and improved tools for OSA screening may
      improve detection.

PMID- 17541664
TI  - Moving beyond empiric continuous positive airway pressure (CPAP) trials for
      central sleep apnea: a multi-modality titration study.
AB  - There is no universally accepted method to determine effective therapy for
      central sleep apnea (CSA). Continuous positive airway pressure (CPAP) applied
      acutely most often does not eliminate apneas and hypopneas. We hypothesized that
      the application of two or more therapeutic modalities after the diagnostic phase
      of polysomnography, a multi-modality titration study (MMTS), would identify a
      successful CSA treatment more often than a standard split-night study (SNS) and
      obviate the need for additional polysomnograms to determine a successful therapy.
      We retrospectively analyzed polysomnograms of patients diagnosed with CSA at our
      Sleep Disorders Center. We defined a therapy trial that resulted in an apnea
      hypopnea index < 10 with at least one treatment modality as a therapeutic
      success. One hundred fifteen patients with CSA were studied. Sixty-six patients
      (57.4%) underwent a SNS, and 49 patients (42.6%) underwent a MMTS. SNS yielded
      only 8/66 (12.1%) successes on the first night, whereas a MMTS yielded 19/49
      (38.8%) successes (p = 0.001, two-tailed Fishers exact). Patients who underwent a
      SNS eventually had similar rate of success as patients studied with MMTS (60.6 vs
      63.3%, NS), but required more testing. Adaptive servo-ventilation was the most
      successful modality tested, yielding 36/46 (78.3%) successes. Trials of
      additional modalities following a failed trial of CPAP often produce a successful
      option that may guide therapy in patients with CSA. This approach may lead to
      establishing the diagnosis and treatment plans faster, while reducing unnecessary
      testing.

PMID- 17541665
TI  - Using mental tasks transitions detection to improve spontaneous mental activity
      classification.
AB  - This paper presents an algorithm based on canonical variates transformation (CVT)
      and distance based discriminant analysis (DBDA) combined with a mental tasks
      transitions detector (MTTD) to classify spontaneous mental activities in order to
      operate a brain-computer interface working under an asynchronous protocol. The
      algorithm won the BCI Competition III--Data Set V: Multiclass Problem, Continuous
      EEG--achieving an averaged classification accuracy over three subjects of 68.65%
      (79.60, 70.31 and 56.02%, respectively) in a three-class problem.

PMID- 17541667
TI  - Analysis of intracranial pressure during acute intracranial hypertension using
      Lempel-Ziv complexity: further evidence.
AB  - We analyzed intracranial pressure (ICP) signals during periods of acute
      intracranial hypertension (ICH) using the Lempel-Ziv (LZ) complexity measure. Our
      results indicate the LZ complexity of ICP decreases during periods of ICH. The
      mean LZ complexity before ICH was 0.20+/-0.04, while the mean LZ complexity
      during ICH was 0.16+/-0.03 (p<0.05). The mean decrease of the LZ complexity
      values during the ICH episodes was 19.5%. Additionally, we present preliminary
      evidence suggesting that periods of ICH may be detectable from non-invasive
      signals coupled with ICP, such as pulse oximetry (SpO2).

PMID- 17541666
TI  - Unravelling the world of cis-regulatory elements.
AB  - Genome-wide comparisons indicate that only studying the coding regions will not
      be enough for explaining the biological complexity of an organism, while the
      genetic variants and the epigenetic differences of cis-regulatory elements are
      crucial to elucidate many complicated biological phenomena. Their various
      regulatory functions also play indispensable roles in forming organismal
      polymorphism. Recent studies showed that the cis-regulatory elements can regulate
      gene expression as nuclear organizers, and involve in functional noncoding
      transcription and produce regulatory noncoding RNA molecules. Novel high
      throughput strategies and in silico analysis make a great amount data of cis
      regulatory elements available. Particularly, the computational methods could help
      to combine reductionist studies with network biomedical investigations, and begin
      the era to understand organismal regulatory events at systems biology level.

PMID- 17541668
TI  - Do K-wires made from shape memory alloys increase pull-out forces? A preliminary
      experimental cadaver study in bovine bone.
AB  - After osteosynthesis of the proximal humerus by Kirschner wires (K-wire),
      loosening and secondary loss can occur. This study tested primary fixation of
      wires made from a shape memory alloy (SMA) Nitinol (NiTi), compared to
      conventional steel K-wires by pull-out tests. Blocks of cancellous bone were
      tested with three wire types: NiTi-K-wire with split apex geometry and
      conventional steel K-wires with and without threads. We found that NiTi-wires can
      be pulled out of bone more easily than steel wires (P=0.05), even though the
      former had rougher surfaces. The application of NiTi-wires through bone produced
      no better stability in comparison to normal steel K-wires, because of triggering
      the memory effect. Further studies are required to determine if NiTi wires of
      another appropriate design, surface and localization are superior to conventional
      wires in the context of this application.

PMID- 17541669
TI  - Implantable stimulator featuring multiple programs, adjustable stimulation
      amplitude and bi-directional communication for implantation in mice.
AB  - We describe an implantable stimulator with adjustable output amplitude and bi
      directional communication at a size of approximately 1 cm(3). The user selects
      from preset patterns of stimulation and adjusts the stimulation amplitude by
      sending coded flashes of light, and receives active confirmation of the chosen
      settings via a powerful LED in the device. These characteristics allow
      selectivity of motor nerve stimulation and minimize unwanted excitation of
      adjacent structures. For example, stimulation of dorsiflexors can be achieved in
      mice without stimulation of plantarflexors. The device can deliver constant
      frequency stimulation as well as burst-like stimulation patterns with adjustable
      ON/OFF times. A lifetime of at least 4 weeks of stimulation at an average
      frequency of 40 Hz can be achieved. The device was built from standard surface
      mount components and encapsulated with biocompatible silicone rubber. The use of
      modern microelectronics allowed us to develop a versatile and highly customizable
      miniature stimulator.

PMID- 17541670
TI  - Dielectric relaxation of a protein-water system in atherosclerotic artery wall.
AB  - Measurements of the dielectric properties of healthy and atherosclerotic human
      artery tissues were made in the frequency range of 100 Hz-100 kHz and
      temperatures from 22 to 260 degrees C. The temperature dependencies of the
      dielectric parameters for healthy tissues reveal distinctively the temperature
      ranges corresponding to the release of water up to 200 degrees C and the
      decomposition processes of elastin and collagen, above this temperature. The
      influence of atherosclerosis on the dielectric properties of artery tissues is
      significant in the whole temperature range. The relative permittivity for
      atherosclerotic tissues at the same temperature is much lower than for the
      healthy tissues. This suggests, that the polarization in atherosclerotic tissues
      due to protons hopping between a smaller number of sites than in healthy tissues,
      as a results of the thermal degradation of collagen-water. The data obtained
      above 200 degrees C indicate that the atherosclerosis induces the higher physico
      chemical changes in the collagen when compared to elastin.

PMID- 17541671
TI  - Effect of training on primary care residents' performance in brief alcohol
      intervention: a randomized controlled trial.
AB  - BACKGROUND: Brief alcohol interventions (BAI) reduce alcohol use and related
      problems in primary care patients with hazardous drinking behavior. The
      effectiveness of teaching BAI on the performance of primary care residents has
      not been fully evaluated. METHODS: A cluster randomized controlled trial was
      conducted with 26 primary care residents who were randomized to either an 8-hour,
      interactive BAI training workshop (intervention) or a lipid management workshop
      (control). During the 6-month period after training (i.e., from October 1, 2003
      to March 30, 2004), 506 hazardous drinkers were identified in primary care, 260
      of whom were included in the study. Patients were interviewed immediately and
      then 3 months after meeting with each resident to evaluate their perceptions of
      the BAI experience and to document drinking patterns. RESULTS: Patients reported
      that BAI trained residents: conducted more components of BAI than did controls
      (2.4 vs 1.5, p = .001); were more likely to explain safe drinking limits (27% vs
      10%, p = .001) and provide feedback on patients' alcohol use (33% vs 21%, p =
      .03); and more often sought patient opinions on drinking limits (19% vs 6%, p =
      .02). No between-group differences were observed in patient drinking patterns or
      in use of 9 of the 12 BAI components. CONCLUSIONS: The BAI-trained residents did
      not put a majority of BAI components into practice, thus it is difficult to
      evaluate the influence of BAI on the reduction of alcohol use among hazardous
      drinkers.

PMID- 17541674
TI  - The lens eyes of the box jellyfish Tripedalia cystophora and Chiropsalmus sp. are
      slow and color-blind.
AB  - Box jellyfish, or cubomedusae, possess an impressive total of 24 eyes of four
      morphologically different types. Compared to other cnidarians they also have an
      elaborate behavioral repertoire, which for a large part seems to be visually
      guided. Two of the four types of cubomedusean eyes, called the upper and the
      lower lens eye, are camera type eyes with spherical fish-like lenses. Here we
      explore the electroretinograms of the lens eyes of the Caribbean species,
      Tripedalia cystophora, and the Australian species, Chiropsalmus sp. using suction
      electrodes. We show that the photoreceptors of the lens eyes of both species have
      dynamic ranges of about 3 log units and slow responses. The spectral sensitivity
      curves for all eyes peak in the blue-green region, but the lower lens eye of T.
      cystophora has a small additional peak in the near UV range. All spectral
      sensitivity curves agree well with the theoretical absorbance curve of a single
      opsin, strongly suggesting color-blind vision in box jellyfish with a single
      receptor type. A single opsin is supported by selective adaptation experiments.

PMID- 17541676
TI  - Segregation and recombination of a multipartite mitochondrial DNA in populations
      of the potato cyst nematode Globodera pallida.
AB  - The discovery that the potato cyst nematode Globodera pallida has a multipartite
      mitochondrial DNA (mtDNA) composed, at least in part, of six small circular
      mtDNAs (scmtDNAs) raised a number of questions concerning the population-level
      processes that might act on such a complex genome. Here we report our
      observations on the distribution of some scmtDNAs among a sample of European and
      South American G. pallida populations. The occurrence of sequence variants of
      scmtDNA IV in population P4A from South America, and that particular sequence
      variants are common to the individuals within a single cyst, is described.
      Evidence for recombination of sequence variants of scmtDNA IV in P4A is also
      reported. The mosaic structure of P4A scmtDNA IV sequences was revealed using
      several detection methods and recombination breakpoints were independently
      detected by maximum likelihood and Bayesian MCMC methods.

PMID- 17541677
TI  - Assessing substitution variation across sites in grass chloroplast DNA.
AB  - We assess the similarity of base substitution processes, described by empirically
      derived 4 x 4 matrices, using chi-square homogeneity tests. Such significance
      analyses allow us to assess variation in sequence evolution across sites and we
      apply them to matrices derived from noncoding sites in different contexts in
      grass chloroplast DNA. We show that there is statistically significant variation
      in rates and patterns of mutation among noncoding sites in different contexts and
      then demonstrate a similar and significant influence of context on substitutions
      at fourfold degenerate sites of coding regions from grass chloroplast DNA. These
      results show that context has the same general effect on substitution bias in
      coding and noncoding DNA: the A+T content of flanking bases is correlated with
      rate of substitution, transition bias, and GC --> AT pressure, while the number
      of flanking pyrimidines on a single strand is correlated with a mutational bias,
      or skew, toward pyrimidines. Despite the similarity in general trends, however,
      when we compare coding and noncoding matrices we find that there is a
      statistically significant difference between them even when we control for
      context. Most noticeably, fourfold degenerate sites in coding sequences are
      undergoing substitution at a higher rate and there are also significant
      differences in the relationship between pyrimidines skew and the number of
      flanking pyrimidines. Possible reasons for the differences between coding and
      noncoding sites are discussed. Furthermore, our analysis illustrates a simple
      statistical way for comparing substitution processes across sites allowing us to
      better study variation in evolutionary processes across a genome.

PMID- 17541678
TI  - The mechanisms of codon reassignments in mitochondrial genetic codes.
AB  - Many cases of nonstandard genetic codes are known in mitochondrial genomes. We
      carry out analysis of phylogeny and codon usage of organisms for which the
      complete mitochondrial genome is available, and we determine the most likely
      mechanism for codon reassignment in each case. Reassignment events can be
      classified according to the gain-loss framework. The "gain" represents the
      appearance of a new tRNA for the reassigned codon or the change of an existing
      tRNA such that it gains the ability to pair with the codon. The "loss" represents
      the deletion of a tRNA or the change in a tRNA so that it no longer translates
      the codon. One possible mechanism is codon disappearance (CD), where the codon
      disappears from the genome prior to the gain and loss events. In the alternative
      mechanisms the codon does not disappear. In the unassigned codon mechanism, the
      loss occurs first, whereas in the ambiguous intermediate mechanism, the gain
      occurs first. Codon usage analysis gives clear evidence of cases where the codon
      disappeared at the point of the reassignment and also cases where it did not
      disappear. CD is the probable explanation for stop to sense reassignments and a
      small number of reassignments of sense codons. However, the majority of sense-to
      sense reassignments cannot be explained by CD. In the latter cases, by analysis
      of the presence or absence of tRNAs in the genome and of the changes in tRNA
      sequences, it is sometimes possible to distinguish between the unassigned codon
      and the ambiguous intermediate mechanisms. We emphasize that not all
      reassignments follow the same scenario and that it is necessary to consider the
      details of each case carefully.

PMID- 17541679
TI  - Inferring the timescale of dengue virus evolution under realistic models of DNA
      substitution.
AB  - Dengue virus (DENV) is the agent of the most widespread vector-borne viral
      disease of humans. To infer the timescale of DENV evolution with as much accuracy
      as possible, we compared, within a Bayesian Markov Chain Monte Carlo (MCMC)
      framework, estimates of phylogenetic tree length using both covarion and
      noncovarion models of molecular evolution, the latter also incorporating lineage
      specific rate variation through a "relaxed" molecular clock. Using a data set of
      32 complete genome sequences representing all four viral serotypes, we found
      evidence for covarion-like evolution at second codon positions in specific DENV
      genes, although rarely at the level of complete gene or genomes. Further, the
      covarion model had little effect on estimates of tree length and hence time to
      the Most Recent Common Ancestor (MRCA). We conclude that although covarion models
      can improve descriptions of the dynamics of amino acid substitution, they have
      little effect on estimates of the timescale of viral evolution, which in the case
      of DENV covers a period of no more than 2000 years.

PMID- 17541680
TI  - The effect of local nucleotides on synonymous codon usage in the honeybee (Apis
      mellifera L.) genome.
AB  - Using all currently predicted coding regions in the honeybee genome, a novel form
      of synonymous codon bias is presented that affects the usage of particular codons
      dependent on the surrounding nucleotides in the coding region. Nucleotides at the
      third codon site are correlated, dependent on their weak (adenine [A] or thyamine
      [T]) versus strong (guanine [G] or cytosine [C]) status, to nucleotides on the
      first codon site which are dependent on their purine (A/G) versus pyrimidine
      (C/T) status. In particular, for adjacent third and first site nucleotides, weak
      pyrimidine and strong-purine nucleotide combinations occur much more frequently
      than the underabundant weak-purine and strong-pyrimidine nucleotide combinations.
      Since a similar effect is also found in the noncoding regions, but is present for
      all adjacent nucleotides, this coding effect is most likely due to a genome-wide
      context-dependent mutation error correcting mechanism in combination with
      selective constraints on adjacent first and second nucleotide pairs within
      codons. The position-dependent relationship of synonymous codon usage is evidence
      for a novel form of codon position bias which utilizes the redundancy in the
      genetic code to minimize the effect of nucleotide mutations within coding
      regions.

PMID- 17541681
TI  - Selective pressures on Drosophila chemosensory receptor genes.
AB  - The evolution and patterns of selection of genes encoding 10 Drosophila odorant
      receptors (Or) and the sex pheromone receptor Gr68a were investigated by
      comparing orthologous sequences across five to eight ecologically diverse species
      of Drosophila. Using maximum likelihood estimates of dN/dS ratios we show that
      all 11 genes sampled are under purifying selection, indicating functional
      constraint. Four of these genes (Or33c, Or42a, Or85e, and Gr68a) may be under
      positive selection, and if so, there is good evidence that 12 specific amino acid
      sites may be under positive selection. All of these sites are predicted to be
      located either in loop regions or just inside membrane spanning regions, and
      interestingly one of the two sites in Gr68a is in a similar position to a
      previously described polymorphism in Gr5a that causes a shift in sensitivity to
      its ligand trehalose. For three Ors, possible evidence for positive selection was
      detected along a lineage. These include Or22a in the lineage leading to D.
      mauritiana and Or22b in the lineage leading to D. simulans. This is of interest
      in light of previous data showing a change in ligand response profile for these
      species in the sensory neuron (ab3A) which expresses both Or22a and Or22b in D.
      melanogaster. In summary, while the main chemosensory function and/or structural
      integrity of these 10 Or genes and Gr68a are evolutionarily preserved, positive
      selection appears to be acting on some of these genes, at specific sites and
      along certain lineages, and provides testable hypotheses for further functional
      experimentation.

PMID- 17541682
TI  - Unilateral adrenal hyperplasia.

PMID- 17541683
TI  - Idiopathic granulomatous mastitis: a heterogeneous disease with variable clinical
      presentation.
AB  - INTRODUCTION: Idiopathic granulomatous mastitis (IGM) is a rare benign
      inflammatory breast disease that presents with variable local manifestations. We
      describe here the different management protocols based on the clinical
      presentation of these patients. METHODS: A retrospective review of 20
      histopathologic confirmed cases of IGM seen over a period of 10 years was
      performed. RESULTS: The median age was 34 years (age range: 21-45 years). All
      were married, parous with history of breast feeding. Ill-defined mass mimicking
      carcinoma was the commonest presentation (70%); however, with the presence of
      signs of inflammation like pain (55%), redness (40%), and peau d'orange (40%), an
      inflammatory process appeared more likely. Axillary lymph node enlargement was
      infrequently seen (40%). Radiologic findings (mammography and ultrasound) were
      nonspecific. Histopathology showed the characteristic lobular distribution of
      granulomatous inflammation in all cases. Surgically, 7 patients had abscess
      drainage with open biopsy, and 7 patients had lumpectomy. Six patients with
      diffuse breast involvement were diagnosed by core needle biopsy only. Microbial
      cultures showed no growth. Antibiotics were given empirically when signs of
      inflammation where present. Two patients needed further abscess drainage followed
      by persistent sinus excision 3-6 weeks later. The median follow-up was 24 months
      (range: 15-42 months). Seventeen patients (85%) were recurrence-free, and 3
      patients (15%) were lost to follow-up. CONCLUSIONS: Management of IGM cases needs
      to be tailored according to the clinical presentation. Precise radiologic and
      pathologic data interpretation by a multidisciplinary breast team will facilitate
      diagnosis and minimize unnecessary intervention.

PMID- 17541684
TI  - Subtotal colectomy with antiperistaltic cecorectal anastomosis in the treatment
      of slow-transit constipation: long-term impact on quality of life.
AB  - BACKGROUND: The aim of the study was to evaluate the effectiveness of subtotal
      colectomy with cecorectal anastomosis (SCCA) in the treatment of slow-transit
      constipation, not just in terms of symptom resolution but also the overall impact
      on patients' quality of life. METHODS: Between 1991 and 2005, 43 patients
      underwent SCCA at our institution, 22 for slow-transit constipation (STC) and 21
      for other types of colic diffuse disease (non-slow-transit constipation: NSTC),
      the latter being considered controls. A total of 29 patients (17 affected by STC)
      were administered a 50-item telephonic questionnaire, including the
      Gastrointestinal Quality of Life Index (GIQLI), the Wexner constipation and
      incontinence scale (WC, WI), and individual willingness to repeat the procedure.
      Questionnaire data and other parameters such as age, sex, length of follow-up,
      complications, and length of hospital stay were analyzed and compared, in order
      to evaluate possible correlations between the parameters and their related impact
      on quality of life, procedural effectiveness in terms of symptomatic regression,
      qualitative differences related to pathology (constipation versus non
      constipation), and surgical approach (laparotomy versus video-laparo-assisted
      procedure). RESULTS: There were no procedure-related deaths in this series
      (mortality: 0%); however, we found two complications in the STC group (9.1%), one
      requiring reoperation. The GIQLI mean score for the STC group was 115.5 +/- 20.5
      (mean score for healthy people 125.8 +/- 13), and the WC mean score passed from a
      preoperative value of 20.3 to a postoperative value of 2.6. Regression analysis
      revealed a significant correlation between GIQLI and urgency and abdominal pain,
      and abdominal pain correlated significantly with pathology (STC). A high number
      of patients (88.2% in STC) expressed a willingness to repeat the procedure given
      the same preoperative conditions. CONCLUSIONS: Comparing our results to those of
      the most homogeneous literature data, SCCA does not appear to be inferior to
      subtotal colectomy with ileorectal anastomosis (IRA) in terms of therapeutic
      effectiveness, postoperative mortality and morbidity, or overall impact on
      quality of life.

PMID- 17541685
TI  - Fine mapping dissects pleiotropic growth quantitative trait locus into linked
      loci.
AB  - A recurring issue in studies of quantitative trait loci (QTLs) is whether QTLs
      that appear to have pleiotropic effects are indeed caused by pleiotropy at single
      loci or by linked QTLs. Previous work identified a QTL that affected tail length
      in mice and the lengths of various bones, including the humerus, ulna, femur,
      tibia, and mandible. The effect of this QTL on tail length has since been found
      to be due to multiple linked QTLs and so its apparently pleiotropic effects may
      have been due to linked QTLs with distinct effects. In the present study we
      examined a line of mice segregating only for a 0.94-Mb chromosomal region known
      to contain a subset of the QTLs influencing tail length. We measured a number of
      skeletal dimensions, including the lengths of the skull, mandible, humerus, ulna,
      femur, tibia, calcaneus, metatarsus, and a tail bone. The QTL region was found to
      have effects on the size of the mandible and length of the tail bone, with little
      or no effect on the other traits. Using a randomization approach, we rejected the
      null hypothesis that the QTL affected all traits equally, thereby demonstrating
      that the pleiotropic effects reported earlier were due to linked loci with
      distinct effects. This result underlines the possibility that seemingly
      pleiotropic effects of QTLs may frequently be due to linked loci and that high
      resolution mapping will often be required to distinguish between pleiotropy and
      linkage.

PMID- 17541686
TI  - Risks of oral sodium phosphate for pre-colonoscopy bowel preparation in children.

PMID- 17541688
TI  - Two percent formalin retention enemas for hemorrhagic radiation proctitis: a
      preliminary report.
AB  - PURPOSE: The short-term safety and efficacy of 2 percent formalin administered as
      a retention enema for hemorrhagic radiation proctitis was studied. METHODS: A
      group of 24 patients with hemorrhagic radiation proctitis who received radical
      radiotherapy were administered 2 percent formalin as a retention enema and the
      treatment was followed up from 1 to 29 (mean, 15.34) weeks. The enema was
      performed on an outpatient basis under sedation with pentazocine and promethazine
      with a retention time of two minutes. The symptoms and proctoscope findings were
      graded and converted into a numeric score, ranging from 1 to 4. The mean
      improvements in scores before treatment and after the last follow-up were
      analyzed for statistical significance by using the paired t-test. RESULTS: There
      was complete cessation of bleeding in 47.8 percent of patients and very
      negligible bleeding in 30.4 percent. A total of 78.2 percent responded positively
      to treatment with 2 percent formalin retention enema. More than one application
      was required in 34.7 percent of the patients. The procedure was well tolerated
      and most of the side effects were mild. Side effects were diarrhea in 23.5
      percent, abdominal pain and tenesmus in 8.8 percent, and fever with vomiting in
      2.9 percent of patients. There was a statistically significant reduction in
      bleeding and proctoscopy scores (P<0.01). None of the patients in this study
      required surgery to palliate their symptoms. CONCLUSIONS: Two percent formalin
      when given as a retention enema is a safe, inexpensive, and effective
      intervention for hemorrhagic radiation proctitis. Any trained health worker using
      simple precautions can perform this procedure. The long-term efficacy and safety
      of 2 percent formalin retention enemas need further assessment with randomized,
      controlled trials.

PMID- 17541690
TI  - Female sex pheromone of the Yunnan pine caterpillar moth Dendrolimus houi: first
      (E,Z)-isomers in pheromone components of Dendrolimus spp.
AB  - The Yunnan pine caterpillar Dendrolimus houi Lajonquiere is a serious defoliator
      of coniferous forests in southwestern China. Gas chromatography
      electroantennography (GC-EAG) analyses of extracts of female sex pheromone glands
      of D. houi moths revealed the presence of three compounds eliciting antennal
      responses. These were identified as (5E,7Z)-5,7-dodecadien-1-ol (E5,Z7-12:OH),
      (5E,7Z)-5,7-dodecadien-1-yl acetate (E5,Z7-12:OAc), and (5E,7Z)-5,7-dodecadienal
      (E5,Z7-12:Ald) by comparison of their GC retention indices, mass spectra, and EAG
      activities with those of synthetic standards. Average amounts of E5,Z7-12:OH,
      E5,Z7-12:OAc, and E5,Z7-12:Ald per calling virgin D. houi female were 14.7 +/-
      12.9 ng (+/- SD), 5.8 +/- 5.4 ng, and 0.8+1.4 ng, respectively, in a ratio of
      100:39.7:5.6. These three components were also collected from the headspace of
      calling virgin female moths by solid-phase microextraction (SPME). In addition,
      trace quantities of (Z)-5-dodecen-1-ol (Z5-12:OH), (5Z,7E)-5,7-dodecadien-1-ol
      (Z5,E7-12:OH), (5E,7E)-5, 7-dodecadien-1-ol (E5,E7-12:OH), (5Z,7E)-5,7-dodecadien
      1-yl acetate (Z5,E7-12:OAc), (5Z,7Z)-5,7-dodecadien-1-yl acetate (Z5,Z7-12:OAc),
      and (5E,7E)-5,7-dodecadien-1-yl acetate (E5,E7-12:OAc) were tentatively
      identified in female pheromone gland extracts by selected ion monitoring GC-MS.
      Field trapping experiments showed that E5,Z7-12:OH, E5,Z7-12:OAc, and E5,Z7
      12:Ald were essential for attraction of male D. houi moths. Traps baited with a
      20:1:1 blend (alcohol/acetate/aldehyde) loaded on gray rubber septa were as
      effective as traps baited with virgin female moths. The optimum ratio of acetate
      to aldehyde was 1:1, and this ratio was more critical than the ratio of either
      compound to the alcohol. This represents the first example of (E,Z)-isomers in
      pheromone blends of Dendrolimus species.

PMID- 17541691
TI  - Toxicity and outcomes associated with surgical cytoreduction and hyperthermic
      intraperitoneal chemotherapy (HIPEC) for patients with sarcomatosis.
AB  - BACKGROUND: Treatment of peritoneal recurrence following surgical resection of
      intra-abdominal sarcomas presents a significant challenge to clinicians.
      Historically, treatment with systemic chemotherapy has been ineffective and
      surgical resection alone has not been durable. We prospectively evaluated the
      feasibility of cytoreductive surgery followed by hyperthermic intraperitoneal
      chemotherapy (HIPEC) with cisplatin (CDDP) alone or in combination with
      mitoxantrone (MITOX) for the treatment of sarcomatosis. METHODS: Two phase I
      trials of HIPEC were conducted (1998-2003). Eligible patients with evidence of
      sarcomatosis underwent cytoreductive surgery followed by HIPEC. In the first
      trial, CDDP dosing was established as 90 mg/m2 with a perfusate time of 90
      minutes and temperature of 41 degrees C. In the second trial, MITOX (20 mg/m2)
      was instilled following perfusion with CDDP. Toxicity, efficacy, and quality of
      life (QOL) were evaluated. RESULTS: A total of 28 patients were enrolled in the
      two trials. We noted a higher overall toxicity score and complication rate with
      combination CDDP/MITOX versus CDDP alone and shorter overall survival duration
      (5.5 months vs 16.9 months, respectively). In addition, local recurrence rates
      were similar in both groups (CDDP 79% vs CDDP/MITOX 68%). As expected, QOL scores
      at 6-8 weeks following HIPEC were 15-25% lower than the baseline scores; however,
      they returned to baseline at 3-6 months. CONCLUSIONS: Although the HIPEC
      technique is feasible for patients with sarcomatosis, it is associated with
      significant toxicity and limited clinical benefit. Combination CDDP/MITOX failed
      to demonstrate any benefit over CDDP alone; moreover, there was an increase in
      toxicity.

PMID- 17541692
TI  - Prophylactic mastectomy in BRCA1/2 mutation carriers and women at risk of
      hereditary breast cancer: long-term experiences at the Rotterdam Family Cancer
      Clinic.
AB  - BACKGROUND: BRCA1/2 mutation carriers and women from a hereditary
      breast(/ovarian) cancer family have a highly increased risk of developing breast
      cancer (BC). Prophylactic mastectomy (PM) results in the greatest BC risk
      reduction. Long-term data on the efficacy and sequels of PM are scarce. METHODS:
      From 358 high-risk women (including 236 BRCA1/2 carriers) undergoing PM between
      1994 and 2004, relevant data on the occurrence of BC in relation to PM,
      complications in relation to breast reconstruction (BR), mutation status, age at
      PM and preoperative imaging examination results were extracted from the medical
      records, and analyzed separately for women without (unaffected, n = 177) and with
      a BC history (affected, n = 181). RESULTS: No primary BCs occurred after PM
      (median follow-up 4.5 years). In one previously unaffected woman, metastatic BC
      was detected almost 4 years after PM (primary BC not found). Median age at PM was
      younger in unaffected women (P < .001), affected women more frequently were 50%
      risk carriers (P < .001). Unexpected (pre)malignant changes at PM were found in
      3% of the patients (in 5 affected, and 5 unaffected women, respectively). In
      49.6% of the women opting for BR one or more complications were registered,
      totaling 215 complications, leading to 153 surgical interventions (71%).
      Complications were mainly related to cosmetic outcome (36%) and capsular
      formation (24%). CONCLUSIONS: The risk of developing a primary BC after PM
      remains low after longer follow-up. Preoperative imaging and careful histological
      examination is warranted because of potential unexpected (pre)malignant findings.
      The high complication rate after breast reconstruction mainly concerns cosmetic
      issues.

PMID- 17541693
TI  - Palliative resection of colorectal cancer: does it prolong survival?
AB  - BACKGROUND: It is still a matter of debate as to whether resective surgery of the
      primary tumor may prolong the survival of patients affected by incurable
      colorectal cancer (CRC). The main goal of this retrospective study, carried out
      on patients not undergoing any therapy other than surgery, was to quantify the
      benefit of primary tumor removal in patients with differently presenting
      incurable CRC. METHODS: One hundred and thirty consecutive patients were operated
      on for incurable CRC (83 undergoing resective and 47 non-resective procedures).
      With the purpose of comparing homogenous populations and of identifying patients
      who may benefit from primary tumor resection, the patients were classified
      according to classes of disease, based on the "metastatic pattern" and the
      "resectability of primary tumor." RESULTS: In patients with "resectable" primary
      tumors, resective procedures are associated with longer median survival than
      after non-resective ones (9 months vs 3). Only patients with distant spread
      without neoplastic ascites/carcinosis benefit from primary tumor removal (median
      survival: 9 months vs 3). Morbidity and mortality of resective procedures is not
      significantly different from that of non-resective surgery, either in the
      population studied or in any of the groups considered. CONCLUSIONS: Palliative
      resection of primary CRC should be pursued in patients with unresectable distant
      metastasis (without carcinomatosis), and, intraoperatively, whenever the primary
      tumor is technically resectable.

PMID- 17541694
TI  - Intraoperative ultrasound localization of nonpalpable breast cancers.
AB  - BACKGROUND: Preoperative localization of nonpalpable breast cancers requires good
      coordination between imaging and surgery departments, and insertion of a guide
      wire can be traumatic for the patient. This study was designed to evaluate the
      efficacy of intraoperative ultrasound localization of nonpalpable breast cancers
      directly by the surgeon. METHODS: This prospective study was conducted from June
      2006 to October 2006 in 70 patients who underwent surgery for nonpalpable
      invasive breast cancer. Ultrasound was performed in the operating room by the
      surgeon with the patient in the operative position. Tumor identification, the
      correlation with tumor diameter on preoperative ultrasound, analysis of resection
      margins, and the need to perform surgical re-excision were analyzed. RESULTS:
      Intraoperative ultrasound identified the target in 67 (95.7%) of 70 patients. Two
      of the three lesions not detected by intraoperative ultrasound were < or =5 mm in
      diameter in patients with a body mass index of > or =25 (normal range, 19-24).
      The correlation with diagnostic ultrasound for tumor dimensions was satisfactory
      (correlation coefficient r = .80). Resection margins free of invasive lesions
      were obtained in 66 cases (94.3%). Three patients (4.3%) required surgical re
      excision, one mastectomy due to multifocal cancer, and two lumpectomy due to
      positive resection margins. CONCLUSIONS: Intraoperative ultrasound localization
      of nonpalpable breast cancers is feasible and effective, with a sensitivity of
      98.3% for tumors >5 mm. It spares the patient the discomfort of a radiological
      and/or supplementary examination with insertion of a guide wire. It also saves
      time and money for hospital teams.

PMID- 17541695
TI  - High risk neurological gait syndrome and vascular dementia.
AB  - We defined a 'high-risk neurological gait' (HRNG) syndrome based on presence of
      any one of hemiparetic, frontal, and unsteady gaits, and examined its validity to
      predict vascular dementia (VD) over 3 and 5 years in 399 nondemented older
      adults, age 75 and over. Cox analysis was used to estimate hazard ratios (HR) for
      VD adjusted for potential confounders. At baseline, 54 subjects had HRNG. 14
      subjects developed VD over 3 years and 25 by 5 years. HRNG predicted risk of VD
      within the first three (HR 3.3, 95% CI 1.8-5.9) and five years (HR 2.7, 95% CI
      1.7-4.2). Including executive dysfunction (Digit symbol scores <16) improved
      validity; subjects with HRNG and executive dysfunction (HR 12.5, 95% CI 5.5-28.4)
      or either (HR 5.9, 95% CI 3.6-9.7) had higher risk of VD over five years.
      Diagnosing HRNG is a clinically relevant approach to identifying older adults at
      high risk of VD over short intervals.

PMID- 17541696
TI  - Acute S-ketamine application does not alter cerebral [18F]altanserin binding: a
      pilot PET study in humans.
AB  - Modeling short-term psychotic states with subanaesthetic doses of ketamine
      provides substantial experimental evidence in support of the glutamate hypothesis
      of schizophrenia. Ketamine exerts its pharmacological effects both directly via
      interactions with glutamate receptors and indirectly by stimulating presynaptic
      release of endogenous serotonin (5-HT). The aim of this feasibility study was to
      examine whether acute ketamine-induced 5-HT release interferes with the binding
      of the 5-HT(2A) receptor (5-HT(2A)R) radioligand [(18)F]altanserin and positron
      emission tomography (PET). Two subjects treated with ketamine and one subject
      treated with placebo underwent [(18)F]altanserin PET at distribution equilibrium
      conditions. Robust physiological, psychopathological and cognitive effects were
      present at ketamine plasma concentrations exceeding 100 microg/l during >70 min.
      Notwithstanding, we observed stable radioligand binding (changes +/-95% CI of 
      1.0 +/- 1.6% and +4.1 +/- 1.8% versus -1.2 +/- 2.6%) in large cortical regions
      presenting high basal uptake of both, [(18)F]altanserin and ketamine. Marginal
      decreases of 4% of radioligand binding were observed in the frontal lobe, and 8%
      in a posteriorily specified frontomesial subregion. This finding is not
      compatible with a specific radioligand displacement from 5-HT(2A)R which should
      occur proportionally throughout the whole brain. Instead, the spatial pattern of
      these minor reductions was congruent with ketamine-induced increases in cerebral
      blood flow observed in a previous study using [(15)O]butanol PET. This may caused
      by accelerated clearance of unspecifically bound [(18)F]altanserin from cerebral
      tissue with increased perfusion. In conclusion, this study suggests that
      [(18)F]altanserin PET is not sensitive to acute neurotransmitter fluctuations
      under ketamine. Advantageously, the stability of [(18)F]altanserin PET towards
      acute influences is a prerequisite for its future use to detect sub-acute and
      chronic effects of ketamine.

PMID- 17541697
TI  - An improved procedure for rapid determination of viral RNA sequences of avian RNA
      viruses.
AB  - A system for rapid determination of viral RNA sequences, RDV, was improved for
      detection of avian RNA virus in allantoic fluids. We detected avian paramyxovirus
      nucleotide sequences using RDV method ver 2.0.

PMID- 17541698
TI  - Even distribution of BK polyomavirus subtypes and subgroups in the Japanese
      Archipelago.
AB  - BK polyomavirus (BKV) is ubiquitous among humans, infecting children
      asymptomatically and then persisting in renal tissue. BKV has four subtypes (I
      IV) that can be identified by serological and genotyping methods. Subtypes I and
      IV are most prevalent in all countries examined to date. Based on nucleotide
      sequence variation, subtype I is further classified into four subgroups (Ia, Ib
      1, Ib-2 and Ic), each of which have a close relationship to a particular human
      population. To clarify the relationships between BKV and human populations, we
      investigated the distribution patterns of BKV subtypes and subgroups in the
      modern Japanese population, which was formed from two distinct ethnic groups.
      Urine samples were collected from immunocompetent elderly patients in six regions
      along the Japanese Archipelago. The 287-bp VP1 region of the viral genome from
      these samples was amplified using the polymerase chain reaction. The amplified
      VP1 regions were sequenced and a neighbor-joining phylogenetic tree was
      reconstructed to classify the BKV isolates. We observed a similar pattern of
      subtype distribution throughout the Japanese Archipelago, with subtype I always
      detected at high rates (67-75%), followed by subtype IV (19-31%), with rare or no
      detection of subtypes II and III. Based on phylogenetic and single nucleotide
      polymorphism analyses, the subtype I isolates were divided into subgroups; the
      percentage of the Ic subgroup was high in all geographic regions (88-100%). These
      results suggest that BKV subtypes and subgroups are evenly distributed in the
      Japanese Archipelago. We discuss the implications of these findings for the
      relationships between BKV and human populations.

PMID- 17541699
TI  - Demarcation of ilarviruses based on the phylogeny of RNA2-encoded RdRp and a
      generic ramped annealing RT-PCR.
AB  - In this study, a generic ramped-annealing (RAN) nested RT-PCR was developed,
      allowing the simultaneous detection and fast characterization of ilarviruses. The
      method involves a one-step RT-PCR in which a pair of degenerate primers amplifies
      a 381-bp part of the polymerase gene (RNA2), followed by a nested PCR
      amplification that increases detection sensitivity. The sensitivity and detection
      range of the method were further increased by applying a ramped annealing
      thermocycling step both in the first RT-PCR and in the subsequent nested PCR. The
      371-bp nested amplicons can be sequenced directly, without cloning, to obtain
      initial sequence information on ilarvirus genomes, or can undergo a restriction
      enzyme analysis for rapid identification of already known virus species.
      Phylogenetic relationships among different members of the family Bromoviridae
      were inferred with maximum likelihood and Bayesian analysis, using published
      homologous partial amino acid sequences corresponding to the nested amplicon and
      also to a longer residue data set (432-453 aa) comprising all possible positions
      of homology among the RNA2-encoded polymerases of members of the family
      Bromoviridae. The implications of these analyses on the taxonomy of ilarviruses
      are discussed. The specific partial polymerase sequence, corresponding to the
      polymerase core palm structure (motifs A-D), was verified as phylogenetically
      informative and can be used to separate ilarviruses from other members of the
      family Bromoviridae, providing initial information for ilarvirus species
      characterization. However, the phylogenetic signal of this region is not reliable
      for inferring relationships among distantly related ilarviruses.

PMID- 17541700
TI  - Using RRT-PCR analysis and virus isolation to determine the prevalence of avian
      influenza virus infections in ducks at Minto Flats State Game Refuge, Alaska,
      during August 2005.
AB  - This study describes surveillance for avian influenza viruses (AIV) in the Minto
      Flats State Game Refuge, high-density waterfowl breeding grounds in Alaska. Five
      hundred paired cloacal samples from dabbling ducks (Northern Pintail, Mallard,
      Green Wing Teal, and Widgeon) were placed into ethanol and viral transport medium
      (VTM). Additional ethanol-preserved samples were taken. Of the ethanol-preserved
      samples, 25.6% were AIV RNA-positive by real-time RT-PCR. The hemagglutinin (HA)
      and neuraminidase (NA) subtypes were determined for 38 of the first-passage
      isolates, and four first-passage isolates could not be definitively subtyped.
      Five influenza A virus HA-NA combinations were identified: H3N6, H3N8, H4N6,
      H8N4, and H12N5. Differences in the prevalence of AIV infections by sex and by
      age classes of Northern Pintail and Mallard ducks were detected, but the
      significance of these differences is undefined. In the 500 paired samples,
      molecular screening detected positive birds at a higher rate than viral isolation
      (chi(2) = 8.35, p = 0.0035, df = 1); however, 20 AIV isolates were recovered from
      PCR-negative ducks. Further research is warranted to compare the two screening
      protocols' potential for estimating true prevalence in wild birds. Our success
      during 2005 indicates Minto Flats will be a valuable study site for a
      longitudinal research project designed to gain further insight into the natural
      history, evolution, and ecology of AIV in wild birds.

PMID- 17541701
TI  - The Polysoft patch: prospective evaluation of feasibility, postoperative pain and
      recovery.
AB  - INTRODUCTION: The Polysoft patch was conceived to associate the advantages of
      placement of the patch in the preperitoneal space (PPS) and easiness of the
      inguinal incision. The aim of this study was to evaluate prospectively the
      feasibility and postoperative outcome of this method. METHODS: Two hundred
      Polysoft repairs were performed in 191 consecutive patients with Nyhus types III
      and IV hernias. The anesthesia was spinal in 146 patients (76.4%), local in 36
      (18.8%) and general in 9 (4.7%). The patch was placed in the PPS through the
      hernial orifice in the fascia in direct hernias and through the internal orifice
      in indirect ones. The technical points and postoperative course data were
      prospectively recorded and postoperative pain was assessed daily by visual
      analogue scale (VAS) in 25 patients. RESULTS: The method was achieved in all the
      cases. The type of the hernias was as follows: 59 direct, 129 indirect (including
      28 pantaloon and 16 sliding), 3 inguino-femoral and 9 recurrent. The size of the
      patch used was medium in 152 cases (76%) and large in 48 (24%). The large patch
      was used more in pantaloon, sliding and inguino-femoral hernias. In direct
      hernias the patch was not split; in indirect hernias the patch was split (so the
      wings recreate a new internal orifice around the spermatic cord) in 79 cases
      (61.2%) and not split (with the cord parietalized) in 50 cases (38.8%). The
      length of operation, postoperative hospital stay, return to daily activity, to
      work and analgesics consumption were [median +/- SD (extremes)]: 35 min +/- 9.1
      (20-60), 1 day +/- 0.4 (0-5), 3 days +/- 1.8 (0-8), 15 days +/- 9.7 (1-30) and 3
      days +/- 2.3 (0-10), respectively. The median number of analgesics units was 8 +/
      5.9 (0-32). The values of pain assessed daily by VAS (on 100) varied from 20.4
      +/- 19.7 (0-60) at day 0, 25.0 +/- 24.5 (0-80) at day 1 to 7.5 +/- 13.7 (0-50) at
      day 7; the mean value for the week was 16.7 +/- 16.7 (0-57). There were 14 (7%)
      benign postoperative complications. CONCLUSION: This study permitted the
      definition of some technical points and showed that the Polysoft patch can be
      used for all types of hernias with a weak posterior wall, including complex cases
      (big scrotal, pantaloon, sliding and recurrent), with a low risk of postoperative
      complications, a low level of postoperative pain and a short recovery time.

PMID- 17541702
TI  - A pragmatic approach to cutaneous nerve division during open inguinal hernia
      repair.
AB  - AIMS: Chronic pain following inguinal hernia repair may be related to the
      handling of cutaneous nerves. This study aims to investigate the frequency of
      cutaneous nerve division in routine practice and the effect that nerve division
      has on long-term pain outcomes. METHODS: The outcomes of 172 patients who
      underwent open inguinal hernia repair over a two-year period during the course of
      a clinical trial were recorded prospectively for 1 year. Pain scores for patients
      in whom one of the nerves was divided were compared with those of patients in
      whom all three were preserved. RESULT: All nerves were preserved in 95 cases
      (55.2%). The ilioinguinal, genital and iliohypogastric nerves were divided in 33
      (19.2%), 12 (7.0%) and 14 (8.1%) cases, respectively. There was no significant
      difference in pain scores between any of the nerve division groups compared to
      the group in which all three were preserved. There were three (1.7%) cases of
      significant chronic pain, two in which no nerves were divided. CONCLUSION: The
      division of cutaneous nerves during inguinal hernia repair has no significant
      effect on postoperative pain. However, there are very few adverse outcomes, and
      so, a pragmatic approach of dividing nerves when they would otherwise be damaged
      may be appropriate.

PMID- 17541703
TI  - Cerebral vascular disease as a cause of postpartum psychosis.

PMID- 17541704
TI  - Stable serum levels of relaxin throughout the menstrual cycle: a preliminary
      comparison of women with premenstrual dysphoria and controls.
AB  - Serum levels of relaxin in 25 women with premenstrual dysphoria and 25 age
      matched controls were determined at three time points during the menstrual cycle.
      At the same time, levels of estradiol, progesterone, 17-beta-OH-progesterone,
      free testosterone, total testosterone, sex hormone binding hormone,
      androstenedione, dehydroepiandrosterone sulphate, and 3-alpha-androstanediol
      glucuronide were determined. Detectable levels of relaxin were found in all women
      in both the follicular and luteal phase as well as around ovulation, the inter
      individual variations being larger than intra-individual differences. The levels
      of relaxin were not influenced by the fluctuation of the other reproductive
      hormones. A significant difference between the two groups of women was observed,
      subjects with premenstrual dysphoria displaying reduced levels of relaxin (p <
      0.05) compared to controls. Also, when analysed with respect to a variable number
      of tandem repeats polymorphism (CT repeats followed by GT repeats) in the
      promotor region of the relaxin H2 gene, women with premenstrual dysphoria (n =
      29) were found to display significantly longer GT repeats than controls (n = 35).

PMID- 17541705
TI  - Isolation of candidate genes for apomictic development in buffelgrass (Pennisetum
      ciliare).
AB  - Asexual reproduction through seeds, or apomixis, is a process that holds much
      promise for agricultural advances. However, the molecular mechanisms underlying
      apomixis are currently poorly understood. To identify genes related to female
      gametophyte development in apomictic ovaries of buffelgrass (Pennisetum ciliare
      (L.) Link), Suppression Subtractive Hybridization of ovary cDNA with leaf cDNA
      was performed. Through macroarray screening of subtracted cDNAs two genes were
      identified, Pca21 and Pca24, that showed differential expression between
      apomictic and sexual ovaries. Sequence analysis showed that both Pca21 and Pca24
      are novel genes not previously characterized in plants. Pca21 shows homology to
      two wheat genes that are also expressed during reproductive development. Pca24
      has similarity to coiled-coil-helix-coiled-coil-helix (CHCH) domain containing
      proteins from maize and sugarcane. Northern blot analysis revealed that both of
      these genes are expressed throughout female gametophyte development in apomictic
      ovaries. In situ hybridizations localized the transcript of these two genes to
      the developing embryo sacs in the apomictic ovaries. Based on the expression
      patterns it was concluded that Pca21 and Pca24 likely play a role during
      apomictic development in buffelgrass.

PMID- 17541706
TI  - AtCPK23 functions in Arabidopsis responses to drought and salt stresses.
AB  - Calcium-dependent protein kinases (CDPKs) are unique serine/threonine kinases in
      plants and there are 34 CDPKs in Arabidopsis genome alone. Although several CDPKs
      have been demonstrated to be critical calcium signaling mediators for plant
      responses to various environmental stresses, the biological functions of most
      CDPKs in stress signaling remain unclear. In this study, we provide the evidences
      to demonstrate that AtCPK23 plays important role in Arabidopsis responses to
      drought and salt stresses. The cpk23 mutant, a T-DNA insertion mutant for AtCPK23
      gene, showed greatly enhanced tolerance to drought and salt stresses, while the
      AtCPK23 overexpression lines became more sensitive to drought and salt stresses
      and the complementary line of the cpk23 mutant displayed similar phenotype as
      wild-type plants. The results of stomatal aperture measurement showed that the
      disruption of AtCPK23 expression reduced stomatal apertures, while overexpression
      of AtCPK23 increased stomatal apertures. The alteration of stomatal apertures by
      changes in AtCPK23 expression may account, at least in partial, for the modified
      Arabidopsis response to drought stress. In consistent with the enhanced salt
      tolerance by disruption of AtCPK23 expression, K(+) content in the cpk23 mutant
      was not reduced under high NaCl stress compared with wild-type plants, which
      indicates that the AtCPK23 may also regulate plant K(+)-uptake. The possible
      mechanisms by which AtCPK23 mediates drought and salt stresses signaling are
      discussed.

PMID- 17541707
TI  - Aerobic biodegradation of tert-butyl alcohol (TBA) by psychro- and thermo
      tolerant cultures derived from granular activated carbon (GAC).
AB  - Tert-butyl alcohol (TBA) is a metabolite of methyl tert-butyl ether and is itself
      possibly a fuel oxygenate. The goals of this study were to enrich and
      characterize TBA-degrading micro-organism(s) from a granular activated carbon
      (GAC) unit currently treating TBA. The results reported herein describe the first
      aerobic, TBA-degrading cultures derived from GAC. Strains KR1 and YZ1 were
      enriched from a GAC sample in a bicarbonate-buffered freshwater medium. TBA was
      degraded to 10% of the initial concentration (2-5 mM) within 5 days after initial
      inoculation and was continuously degraded within 1 day of each re-amendment.
      Resting cell suspensions mineralized 70 and 60% of the TBA within 24 h for KR1
      and YZ1, respectively. Performance optimization with resting cells was conducted
      to investigate kinetics and the extent of TBA degradation as influenced by
      oxygen, pH and temperature. The most favorable temperature was 37 degrees C;
      however, TBA was degraded from 4 to 60 degrees C, indicating that the culture
      will sufficiently treat groundwater without heating. This is also the first
      report of psychrotolerant or thermotolerant TBA biodegradation. The pH range for
      TBA degradation ran from 5.0 to 9.0. Phylogenetic data using a partial 16S rRNA
      gene sequence (570 bases) suggest that the primary members of KR1 and YZ1 include
      uncharacterized organisms within the genera Hydrogenophaga, Caulobacter, and
      Pannonibacter.

PMID- 17541708
TI  - Bioremediation of polycyclic aromatic hydrocarbons contaminated soil with
      Monilinia sp.: degradation and microbial community analysis.
AB  - Microcosms were set up with a PAHs-contaminated soil using biostimulation
      (addition of ground corn cob) and bioaugmentation (inoculated with Monilinia sp.
      W5-2). Degradation of polycyclic aromatic hydrocarbons and microbial community
      were examined at the end of incubation period. After 30 days, bioaugmented
      microcosms showed a 35+/-0% decrease in total PAHs, while biostimulated and
      control microcosms showed 16+/-9% and 3+/-0% decrease in total PAHs,
      respectively. Bioaugmented microcosms also revealed 70+/-8% and 72+/-2% decreases
      in benzo[a]pyrene and anthracene, respectively, while the values for
      biostimulated and control microcosms were much lower. Detoxification of soils in
      bioaugmented microcosms was confirmed by genetic toxicity assay, suggesting
      important role of fungal remediation. Molecular fingerprint profiles and
      selective enumeration showed biostimulation with ground corn cob increased both
      number and abundance of indigenous aromatic hydrocarbons degraders and changed
      microbial community composition in soil, which is beneficial to natural
      attenuation of PAHs. At the same time, bioaugmentation with Monilinia strain W5-2
      imposed negligible effect on indigenous microbial community. This study suggests
      that fungal remediation is promising in eliminating PAHs, especially the part of
      recalcitrant and highly toxic benzo[a]pyrene, in contaminated soil. It is also
      the first description of soil bioremediation with Monilinia sp.

PMID- 17541709
TI  - Breast cancer metastasis to bone: evaluation of bioluminescent imaging and
      microSPECT/CT for detecting bone metastasis in immunodeficient mice.
AB  - This study sought to determine if weekly X-ray exposure affected breast cancer
      cell metastasis to bone and to also evaluate the use of bioluminescent imaging
      (BLI) and microSPECT for detection of metastatic bone lesions. Five week old nude
      mice were randomly assigned to the CT exposed (n = 7) and no CT exposure (n = 6)
      treatment groups. Mice received an intracardiac injection of MDA-MB-435 human
      breast cancer cells transduced with luciferase, or a sham injection (saline). The
      CT exposed group of mice received CT irradiation once a week for 5 weeks. All
      mice underwent weekly BLI and select mice received Tc-99m-MDP followed by
      microSPECT imaging after 5 weeks. Pathological evaluation and histomorphometry
      were used to assess the affect of CT X-rays on bone metastasis and to evaluate
      BLI. BLI results found no significant difference in metastasis between animals
      that received CT and those that did not (P > 0.05); however, histomorphometry of
      the knee joints revealed a significant increase (P = 0.029) in tumor area of the
      leg bones in mice that received CT exposure (60% +/- 7%) compared to animals that
      did not receive CT scans (33% +/- 8%). Compared to histological analysis, BLI of
      the leg and spine was determined to have excellent sensitivity (100%), good
      specificity (80-90%) and accuracy (90-96%), a positive predictive value of 81-93%
      and a 100% negative predictive value. Thus, multi-modality imaging techniques can
      be very useful for monitoring bone metastasis, however microCT X-rays should be
      used judiciously in order to limit irradiation that may stimulate increased
      metastasis to specific regions of the skeleton. MicroSPECT imaging did not detect
      metastatic lesions in the legs of these young nude mice.

PMID- 17541710
TI  - An improved method to study NK-independent mechanisms of MTLn3 breast cancer lung
      metastasis.
AB  - To study the tumor cell autonomous processes of metastasis, an in vivo tumor
      metastasis model is required that excludes the involvement of the innate immune
      system. For this purpose we used the established syngeneic MTLn3 cell - Fischer
      344 tumor model. MTLn3 cells are efficiently eradicated by NK cells in vivo.
      Using isolated cell systems, we provide evidence for apoptosis-induction by IL-2
      activated NK cells, but not T-cells, despite the expression of MHC class I. This
      is largely mediated by the perforin/granzyme B pathway in MTLn3 cells in a
      caspase-dependent manner. Temporal in vivo depletion of NK cells by an antibody
      based method, dramatically improved colonization of the lungs by MTLn3 cells,
      from 5 metastases in the untreated animals to 130 metastases in the NK-depleted
      animals. Thus, we improved the syngeneic MTLn3-Fischer 344 tumor model by
      temporal depletion of NK cells of which the advantages over the use of
      immunodeficient animals are evident.

PMID- 17541711
TI  - Interstitial Cajal-like cells in human gallbladder.
AB  - We describe here an interstitial Cajal-like cell type (ICLC) in human
      gallbladder, resembling the archetypal enteric interstitial cells of Cajal.
      Gallbladder ICLC were demonstrated in fresh preparations (tissue cryosections)
      using methylene-blue, and fixed specimens in Epon semi-thin sections stained with
      toluidine blue or transmission electron microscopy (TEM). The positive diagnosis
      of gallbladder ICLC was further verified by immunohistochemistry: CD117/c-kit,
      CD34, and another 16 antigens: vimentin, desmin, nestin, alpha-smooth muscle
      actin, NK-1, S-100, PGP-9.5, tau protein, chromogranin A, NSE, GFAP, CD1a, CD62
      P, CD68, estrogen and progesterone receptors. Double immunostaining was performed
      for CD117, CD34 and CD117 and nestin, respectively. In fresh specimens, the
      spatial density of gallbladder ICLC was 100-110 cells/mm(2). ICLC mainly appeared
      beneath the epithelium and in muscularis (about 7%, and approximately 5%,
      respectively). In toto, ICLC represent in gallbladder approximately 5.5% of
      subepithelial cells. TEM showed that diagnostic criteria were fulfilled by ICLC.
      Moreover, TEM indicated that the main ultrastructural distinctive feature for
      ICLC, the cell processes, develop into the characteristic shape at a relatively
      early stage of development. It remains to be established if, in humans, ICLC are
      involved in gallbladder (dis)functions (e.g. pace-making, secretion (auto-, juxta
      and/or paracrine), intercellular signaling, or stone formation).

PMID- 17541712
TI  - Nucleotide-induced and actin-induced structural changes in SH1-SH2-modified
      myosin subfragment 1.
AB  - We compared the structural properties of myosin subfragment 1 (S1) modified at
      both reactive SH-groups, SH1 (Cys707) and SH2 (Cys697), with the properties of
      unmodified S1 and SH1-modified S1. It is shown using differential scanning
      calorimetry (DSC) that SH1 modification has no noticeable influence on the
      changes in S1 thermal unfolding induced by the formation of S1 ternary complexes
      with ADP and P(i) analogs (V(i), AlF(4)(-), and BeF(x)). These changes, however,
      normally expressed in a significant increase of S1 thermal stability, are almost
      fully prevented by modification of both SH1 and SH2. In contrast, SH2
      modification had no effect on the changes induced by the formation of the ternary
      complexes S1-ADP-V(i), S1-ADP-AlF(4)(-), and S1-ADP-BeF(x) in EPR spectra of S1
      spin-labeled at SH1 group. Interaction of S1 with F-actin substantially increased
      the thermal stability of S1; a similar effect was observed by DSC with both SH1-
      and SH1-SH2-modified S1. Overall, our results demonstrate that modification of
      both reactive SH-groups on S1 has no influence on the actin-induced changes of S1
      and on the local nucleotide-induced conformational changes in the SH1 group
      region, but strongly prevents the global nucleotide-induced structural changes in
      the entire S1 molecule. The results suggest that modification of SH1 and SH2
      impairs the spread of nucleotide-induced conformational changes from the ATPase
      site throughout the structure of the entire S1 molecule, thus disturbing a
      coupling between the motor and regulatory domains in the myosin head.

PMID- 17541713
TI  - Normality of upper and lower peripheral pulse transit time of normotensive and
      hypertensive children.
AB  - OBJECTIVES: The ankle-brachial index (ABI) is known to be indicative of sub
      clinical peripheral arterial diseases that are correlated with cardiovascular
      disease risk factors like atherosclerosis or ischemic extremity. Due to its
      occluding measurement nature, this may not be appealing to less cooperative
      patients when multiple prolonged screening is required. A simple and non
      intrusive approach termed pulse transit time ratio (PTTR) has recently shown to
      be potential surrogate marker for the prolonged ABI measurement. Other studies
      have also suggested that subjects with hypertension have stiffer arterial wall
      and thereby can confound transit time related parameters. Thus, it becomes
      important to understand the PTTR normality and difference of hypertensive
      children when compared to those measured from normotensive children. METHODS:
      About 55 normotensive (39 male; aged 8.4 +/- 2.3 yr) and 4 hypertensive (4 male;
      aged 5-10 yr) Caucasian children were recruited from the same geographical
      location. A customized device was used to compute pulse transit time related
      measurements. Since the PTTR approach produced a delta value that was similar to
      that of ABI, possible inter-subject physiologic differences had limited
      confounding effects on the derived PTTR parameter. RESULTS: The obtained transit
      time measurements from the hypertensive children had lower pulse transit time
      value when compared to their normotensive counterparts. However, the statistical
      analysis indicated that they had insignificant PTTR difference (p > 0.01) from
      those seen in the normotensive children. CONCLUSIONS: The findings herein suggest
      that stiffer arterial wall may have confounding effects on the derived transit
      time related measurements but it is limited on the PTTR parameter. Similar to the
      ABI approach, PTTR may be only confounded by abnormal local changes in either of
      the measured peripheral arterial wall. Hence, the PTTR technique shows promise to
      be an ABI marker from this perspective.

PMID- 17541714
TI  - Reliability of continuous pulse contour cardiac output measurement during
      hemodynamic instability.
AB  - OBJECTIVE: Arterial pulse contour analysis is gaining widespread acceptance as a
      monitor of continuous cardiac output (CO). While this type of CO measurement is
      thought to provide acceptable continuous measurements, only a few studies have
      tested its accuracy and repeatability under unstable hemodynamic conditions. We
      compared continuous CO measurement using the pulse contour method (PCCO) before
      and after calibration with intermittent transpulmonary thermodilution cardiac
      output (TpCO). METHOD: We compared the two methods of CO measurements in 15
      Landrace pigs weighing 20-25 kg in an experimental model of sepsis. Nine pigs
      were given an infusion of E. coli lipopolysacchride (LPS), and six pigs acted as
      controls. PCCO values before and after calibration (PCCO1 and PCCO2 respectively)
      were registered, and their errors relative to TpCO measurements were compared.
      RESULTS: The mean coefficient of variation for repeated PCCO measurements was
      6.85% for the control group, and 13.99% for the endotoxin group. The range of
      TpCO was 1.01-3.15 L/min. In the control group the bias +/-2SD was 0.11 +/- 0.53
      L/min (TpCO vs PCCO1) and -0.02 +/- 0.38 L/min (TpCO vs PCCO2). In the endotoxin
      group, the agreement was poor between TpCO and PCCO1, 0.08 +/- 1.02 L/min. This
      improved after calibration (TpCO vs PCCO2) to 0.01 +/- 0.31 L/min. CONCLUSIONS:
      In hemodynamically stable pigs, both pre- and post-calibration PCCO measurements
      agreed well with the intermittent transpulmonary thermodilution technique.
      However, during hemodynamic instability, and pre-calibration PCCO values had wide
      limits of agreement compared with TpCO. This was reflected by larger coefficients
      of variation for PCCO in hemodynamic instability. The error of PCCO measurement
      improved markedly after calibration, with bias and limits of agreement within
      clinically acceptable limits.

PMID- 17541715
TI  - Cardiac output derived from left ventricular pressure during conductance catheter
      evaluations: an extended Modelflow method.
AB  - OBJECTIVE: The Modelflow method computes cardiac output (CO) from arterial
      pressure (CO-MFao) by simulating a non-linear three-element Windkessel model of
      aortic input impedance. We present a novel technique to apply the Modelflow
      method to the left ventricular pressure (Plv) signal, to obtain an estimation of
      CO (CO-MFlv). METHODS: We extended the model by simulating the aortic valve as a
      resistance placed in series to the characteristic impedance. In our model the
      valve resistance is infinite in diastole, while it has a patient related value
      during systole. Twenty one patients with heart failure were studied with a
      combined pressure-conductance catheter positioned in the left ventricle and a
      micromanometer in the aorta. CO changes were induced during temporary sequential
      atrio-biventricular pacing with different atrio-ventricular and inter-ventricular
      intervals. After a single calibration we compared CO-MFlv with CO-MFao (516
      measurement series) and with CO estimated by the conductance catheter volume
      technique (CO-cond) (267 series). RESULTS: CO ranged from 2.42 to 7.59 l/min with
      an overall mean of 4.36 (1.38) l/min. Comparing the two Modelflow methods, the
      bias was -0.04 (0.36) l/min, with limits of agreement of -0.77 and 0.70 l/min,
      and a coefficient of variation of 8.4%. Of the 516 changes in CO from baseline
      values, 112 were greater than 0.5 l/min and 110 of these (98%) were scored in the
      same direction by both methods. For comparisons between CO-MFlv and CO-cond the
      bias was -0.10 (0.49), with limits of agreement of -1.12 and 0.90 l/min, and a
      coefficient of variation of 12.5%. CONCLUSIONS: Cardiac output estimates by the
      modelflow method from aortic pressure and left ventricular pressure are
      interchangeable in patients without mitral and aortic abnormalities. After an
      initial calibration, CO-MFlv presents near zero bias and an adequate precision.

PMID- 17541716
TI  - Transgenic embryos and mice produced from low titre lentiviral vectors.
AB  - Lentiviral vectors are now recognised as an efficient transgene delivery system
      which can result in greater than 90% of founder animals carrying the transgene.
      Vector injection into the perivitelline space has emerged as the standard
      delivery method but is limited by the need for high-titre lentivirus vector
      preparations. Based on a modified perivitelline injection method we demonstrate
      that transgenic animals can be generated from low-titre virus vector preparations
      further simplifying lentiviral transgenesis. Repeat injection of 10(7) TU/ml
      vector preparation resulted in 23% of embryos carrying the transgene compare to
      1% from a single injection. Embryos exposed to repeat injection of vector
      developed to blastocyst with the same efficiency as non-injected embryos and
      produced transgenic mice capable of transmitting the transgene through the
      germline.

PMID- 17541717
TI  - Excision of the Frt-flanked neo (R) cassette from the CD19cre knock-in transgene
      reduces Cre-mediated recombination.
AB  - Intercross of mice transgenic for Flp-recombinase with the CD19cre mouse strain
      leads to excision of the Frt-flanked neo (R) cassette from the CD19cre knock-in
      transgene. This significantly reduces the expression level of Cre by the CD19cre
      transgene and consequently decreases the extent of Cre-mediated recombination of
      loxP-flanked alleles, most likely due to the fact that this neo (R) cassette
      contains polyoma enhancer sequences. We wish to draw attention to this finding,
      since the Flp-deleter mouse strain is commonly used to remove Frt-flanked
      selection cassettes in vivo from conditional alleles. Therefore conditional
      alleles have to be separated from the Flp-deleter transgene by breeding before
      crosses with CD19cre mice are initiated. In addition our findings suggest that
      gene expression from the CD19 locus can be increased by the insertion of
      exogenous enhancer sequences, without compromising B cell specificity.

PMID- 17541718
TI  - Over expression of cytosolic copper/zinc superoxide dismutase from a mangrove
      plant Avicennia marina in indica rice var Pusa Basmati-1 confers abiotic stress
      tolerance.
AB  - Antioxidant enzymes play an important role in conferring abiotic stress
      tolerance. Superoxide dismutase (SOD) is the first enzyme in the enzymatic
      antioxidative pathway. Halophytic plants like mangroves have been reported to
      have a high level of SOD activity, which plays a major role in defending the
      mangrove species against severe abiotic stresses. We had previously reported the
      isolation of Sod1, a cDNA encoding a cytosolic copper zinc superoxide dismutase
      from the mangrove plant Avicennia marina and its mRNA expression pattern during
      various oxidative and abiotic stresses. The present study is an extension of the
      previous study in further characterizing the Sod1 cDNA by transforming it into
      rice and analysing the transgenic plants for abiotic stress tolerance. Southern
      hybridization of A. marina genomic DNA using Sod1, revealed that this gene in A.
      marina genome is present as a single copy. The cDNA was cloned into a binary
      vector (pCAMBIA 1300) and transformed into indica rice var Pusa Basmati-1.
      Southern hybridization analysis of transgenic rice plants revealed stable
      integration of the Sod1 transgene in the rice genome. The mRNA transcript of Sod1
      was detected by Northern hybridisation in the transgenic rice plants. SOD isozyme
      assay of the transgenic rice plants revealed the stable expression of the
      transgenic Sod1 protein. The transgenic plants were more tolerant to methyl
      viologen mediated oxidative stress in comparison to the untransformed control
      plants. The transgenic plants also withstood salinity stress of 150 mM of NaCl
      for a period of eight days while the untransformed control plants wilted at the
      end of the stress treatment in hydroponics. Pot grown transgenic plants could
      also tolerate salinity stress better than the untransformed control plants, when
      irrigated with saline water. The transgenic plants also revealed better tolerance
      to drought stress in comparison to untransformed control plants.

PMID- 17541719
TI  - Evaluation of CRE-mediated excision approaches in Arabidopsis thaliana.
AB  - The ability of the CRE recombinase to catalyze excision of a DNA fragment flanked
      by directly repeated lox sites has been exploited to modify gene expression and
      proved to function well in particular case studies. However, very often
      variability in CRE expression and differences in efficiency of CRE-mediated
      recombination are observed. Here, various approaches were investigated to
      reproducibly obtain optimal CRE activity. CRE recombination was analyzed either
      by transforming the CRE T-DNA into plants containing a lox-flanked fragment or by
      transforming a T-DNA harboring a lox-flanked fragment into plants producing the
      CRE recombinase. Although somatic CRE-mediated excision of a lox-flanked fragment
      was obtained in all transformants, a variable amount of germline-transmitted
      deletions was found among different independent transformants, irrespective of
      the orientation of transformation. Also, the efficiency of CRE-mediated excision
      correlated well with the CRE mRNA level. In addition, CRE-mediated fragment
      excision was compared after floral dip and after root tissue transformation when
      transforming in a CRE-expressing background. Importantly, less CRE activity was
      needed to excise the lox-flanked fragment from the transferred T-DNA after root
      tissue transformation than after floral dip transformation. We hypothesize that
      this is correlated with the lower T-DNA copy number inserted during root
      transformation as compared to floral dip transformation.

PMID- 17541720
TI  - Salt tolerance conferred by overexpression of Arabidopsis vacuolar Na(+)/H (+)
      antiporter gene AtNHX1 in common buckwheat (Fagopyrum esculentum).
AB  - Agriculture productivity is severely affected by soil salinity. One possible
      mechanism by which plants could survive salt stress is to compartmentalize sodium
      ions away from the cytosol. In the present work, transgenic buckwheat plants
      overexpressing AtNHX1, a vacuolar Na(+)/H(+) antiporter gene from Arabidopsis
      thaliana, were regenerated after transformation with Agrobacterium tumefaciens.
      These plants were able to grow, flower and accumulate more rutin in the presence
      of 200 mmol/l sodium chloride. Moreover, the content of important nutrients in
      buckwheat was not affected by the high salinity of the soil. These results
      demonstrated the potential value of these transgenic plants for agriculture use
      in saline soil.

PMID- 17541721
TI  - Pollen-mediated intraspecific gene flow from herbicide resistant oilseed rape
      (Brassica napus L.).
AB  - The cultivation of genetically modified (GM) herbicide resistant oilseed rape
      (Brassica napus) has increased over the past few years. The transfer of herbicide
      resistance genes via pollen (gene flow) from GM crops to non-GM crops is of
      relevance for the realisation of co-existence of different agricultural
      cultivation forms as well as for weed management. Therefore the likelihood of
      pollen-mediated gene flow has been investigated in numerous studies. Despite the
      difficulty to compare different experiments with varying levels of outcrossing,
      we performed a literature search for world-wide studies on cross-fertilisation in
      fully fertile oilseed rape. The occurrence and frequency of pollen-mediated
      intraspecific gene flow (outcrossing rate) can vary according to cultivar,
      experimental design, local topography and environmental conditions. The
      outcrossing rate from one field to another depends also on the size and
      arrangement of donor and recipient populations and on the ratio between donor and
      recipient plot size. The outcrossing levels specified in the presented studies
      are derived mostly from experiments where the recipient field is either
      surrounding the donor field (continuous design) or is located as a patch at
      different distances from the donor field (discontinuous design). Reports of gene
      flow in Brassica napus generally show that the amount of cross-fertilisation
      decreases as the distance from the pollen source increases. The evidence given in
      various studies reveals that the bulk of GM cross-fertilisation occurs within the
      first 10 m of the recipient field. The removal of the first 10 m of a non
      transgenic field facing a GM crop might therefore be more efficient for reducing
      the total level of cross-fertilisation in a recipient sink population than to
      recommend separation distances. Future experiments should investigate cross
      fertilisation with multiple adjacent donor fields at the landscape level under
      different spatial distributions of rapeseed cultivars and different cropping
      systems. The level of cross-fertilisation occurring over the whole field is
      mainly important for co-existence and has not been investigated in agricultural
      scale experiments until now. Potential problems with herbicide resistant oilseed
      rape volunteers arising from intraspecific gene flow can be largely solved by the
      choice of suitable cultivars and herbicides as well as by soil management.

PMID- 17541722
TI  - Can intravenous immunoglobulin and simvastatin solve the problem of sensitization
      in renal transplant candidates?
AB  - The value of intravenous immunoglobulin (IVIG) and simvastatin as potential
      modalities for the treatment of sensitized patients was evaluated by testing the
      efficacy of these agents on a relatively large cohort of adult hemodialysis
      patients (11) who were waiting for renal allotransplantation at our center. The
      patients had persistently positive crossmatches with their living related donors
      and a panel reactive antibody titer of more than 20%. All patients received IVIG
      (500 mg/kg per day on alternate days for a total of six doses); panel reactive
      antibody (PRA) titer and crossmatch testing were carried out after each dose and
      before each subsequent one. Two months after the last dose, eight patients
      received simvastatin (20 mg/day) for a period of 2 months; PRA titer and
      crossmatch testing were carried out every two weeks. Only four patients showed an
      insignificant reduction of PRA activity (P = 0.36); no patient attained a
      negative crossmatch. Simvastatin also resulted in an insignificant reduction of
      anti-human leukocyte antigen (HLA) antibodies in three patients (P = 0.32). We
      propose that IVIG or simvastatin alone can not effectively inhibit preformed anti
      HLA antibodies to allow successful renal transplantation. Further trials on the
      use of IVIG and simvastatin with other modalities of treatment to desensitize
      these patients may be warranted.

PMID- 17541723
TI  - Correlation of the myocardial performance index with plasma B-type natriuretic
      peptide levels in patients with mitral regurgitation.
AB  - OBJECTIVE: The Myocardial performance index (MPI) is an echocardiographic index
      of combined systolic and diastolic function, calculated as isovolumetric
      relaxation time plus isovolumetric contraction time divided by ejection time. The
      aim of this study was to define the correlation of the MPI with plasma B-type
      natriuretic peptide (BNP) levels and echocardiographic parameters in patients
      with chronic mitral regurgitation (MR). METHODS: About 33 patients with at least
      moderate MR of organic etiology were enrolled to the study. All patients
      undergone complete 2D and Doppler echocardiography. Plasma BNP levels were
      studied. RESULTS: BNP levels in NYHA classes I-III were 9.3 +/- 2.2 pg/ml, 61.3
      +/- 12.2 pg/ml, and 199.6 +/- 55.2 pg/ml, respectively (I vs. II P < 0.001, I vs.
      III P < 0.001 and II vs. III P = 0.004). Myocardial performance index were 0.42
      +/- 0.02, 0.49 +/- 0.02, and 0.52 +/- 0.03 in MR patients with NYHA I-III,
      respectively. MPI was significantly higher in patients with NYHA class III
      compared to NYHA I (P = 0.001) and NYHA II (P = 0.005). There were no
      correlations between MPI and left atrial diameter, MR jet area, MR index and
      systolic pulmonary artery pressure whereas left ventricle (LV) end-systolic
      volume (r = 0.38), LV end-diastolic volume (LVDV) (r = 0.40), LV ejection
      fraction (r = -0.59), NYHA class (r = 0.51) and plasma BNP levels (r = 0.67) were
      strongly correlated. Only independent variable affecting MPI was plasma BNP level
      (odds ratio [CI]: 2.18[0.002-0.098], P = 0.041). CONCLUSIONS: MPI is a powerful
      index in assessing the severity of left ventricular function and symptom severity
      in patients with MR. Plasma BNP is an independent predictor of MPI where both
      parameters assess combined systolic and diastolic LV function, effectively.

PMID- 17541724
TI  - Adenosine stress first pass perfusion for the detection of coronary artery
      disease in patients with aortic stenosis: a feasibility study.
AB  - PURPOSE: Detection of coronary artery disease (CAD) with magnetic resonance
      imaging (MRI) using adenosine stress first pass perfusion in patients with aortic
      stenosis in comparison with invasive angiography. Twenty-three consecutive
      patients (15 male, mean age 68 +/- 12 years) with relevant aortic stenosis
      (aortic valve area 0.90 +/- 0.41 cm(2)) were examined by MRI (1.5 T, Philips
      Intera CV). Contrast-enhanced first pass perfusion was performed with adenosine
      stress (140 microg/kg/min) and under rest conditions. The results were compared
      with invasive coronary angiography with regard to the presence of a relevant
      coronary artery stenosis (>70%). Three of 23 patients (13%) had contraindications
      for adenosine administration (one patient with atrioventricular block, two
      patients with mild claustrophobia). In the remaining 20 patients, adenosine
      stress perfusion could be performed without any complications. CAD was correctly
      detected in eight patients and correctly ruled out in 10 of 12 patients. False
      positive results were seen in two patients with severe myocardial hypertrophy.
      Sensitivity, specificity, positive predictive value, and negative predictive
      value were 100%, 80%, 83%, and 100%, respectively. Adenosine stress perfusion can
      be performed without complications even in patients with high grade aortic
      stenosis. MRI is helpful to detect and rule out significant CAD in these
      patients. Severe myocardial hypertrophy may lead to false-positive results. Our
      initial results indicate that due to a high negative predictive value pre
      operative invasive coronary angiography might probably be waived in patients
      without perfusion defects in stress MRI.

PMID- 17541725
TI  - Angiographic and 3D intravascular ultrasound assessment of overlapping bare metal
      stent and three different formulations of drug-eluting stents in patients with
      diabetes mellitus.
AB  - OBJECTIVES: The aim of this study was to examine the impact of overlapping bare
      metal stent (BMS) and three different formulations of drug-eluting stent (DES) on
      intimal hyperplasia (IH) response of patients with diabetes mellitus (DM).
      METHODS: Forty-nine DM patients treated with overlapping BMS (19 lesions),
      sirolimus-eluting stent (SES 12 lesions), paclitaxel-eluting stent (PES 8
      lesions) or tacrolimus-eluting stent (TES 10 lesions) were studied. Baseline and
      9-month follow-up volumetric intravascular vascular ultrasound (IVUS) and
      quantitative coronary angiography (QCA) analysis were performed in the entire
      stented segment and in the overlapped (OL) and non-overlapped (non-OL)
      subsegments. Clinical outcomes were evaluated at 1-year follow-up. RESULTS: Post
      procedure (PO-) QCA measurements were similar in all stent groups, and between OL
      and non-OL subsegments in each individual type of stents. Percent IH was lower in
      SES and PES vs. BMS (p < 0.05). Percent IH was significantly greater in OL
      subsegment compared with non-OL subsegment in BMS (p < 0.05), but not in all type
      of DES groups. SES showed significantly less %IH compared with PES and TES in OL
      and non-OL subsegments. Vessel area at the OL remained unchanged from PO to FU in
      all type of DES and BMS groups. There were no aneurysm formation and no stent
      thrombosis up to 1-year follow-up. CONCLUSIONS: Overlapping BMS is associated
      with enhanced IH response in diabetic patients, whereas overlapping DES,
      particularly SES and PES, appear effective to inhibit IH without detectable late
      vascular adverse effects.

PMID- 17541726
TI  - Focal macroscopic fat deposition within the right ventricular wall in
      asymptomatic patients undergoing screening EBCT coronary calcium scoring
      examinations.
AB  - PURPOSE: Macroscopic focal fat deposition within the wall of the right ventricle
      (RV) has been historically associated with arrhythmogenic right ventricular
      dysplasia (ARVD). We attempt to characterize the incidence of macroscopic RV fat
      detected as an incidental imaging finding on electron beam computer tomography
      (EBCT). METHODS: A total of 165 patients were imaged. Their electronic medical
      records and imaging studies were reviewed for age, gender, body-mass index, the
      presence of focal fat in the RV wall, and additional thoracic fatty
      proliferation. RESULTS: A set of 28 patients (17%) had macroscopic fat along the
      RV wall. The mean age of the patients with fatty deposition was 58.6 +/- 9.9,
      compared with 54.4 +/- 9.9 for patients without it. The difference in incidence
      of the finding by mean age was statistically significant (P-value = 0.045). When
      grouped according to their Body Mass Index (BMI), there was no statistical
      association between the BMI category and the presence of focal fat deposition (P
      = 0.23). CONCLUSION: Macroscopic fatty deposition of the RV wall is a common
      incidental imaging finding in up to 17% of patients that increases in prevalence
      as age advances.

PMID- 17541727
TI  - An integrated approach to determine left atrial volume, mass and function in
      hypertrophic cardiomyopathy by two-dimensional echocardiography.
AB  - METHODS: The study included 25 hypertrophic cardiomyopathy (HCM) patients (15 non
      obstructive and 10 obstructive) and 25 controls for assessment of left atrial
      (LA) volume, mass and function by two-dimensional echocardiography. Measurement
      included mean LA diameter (LAD), LA mass = {(mean LAD + anterior LA wall +
      posterior LA wall)3 - mean LAD3} x 0.8 + 0.6, LA volume = [(8/3 pi L . A1 . A2),
      where L is LA length, A1 and A2 are LA area in 4-chambers and 2-chambers,
      respectively] including maximum (V max), minimum (V min), and pre-atrial
      contraction (V pre-A), total atrial stroke volume (TA-SV), TA emptying fraction
      (TA-EF), active atrial SV (AA-SV), AA-EF, passive atrial SV (PA-SV), PA-EF,
      atrial expansion index (AEI), and LA kinetic energy (LA-KE) = (1/2) x AA-SV x P x
      V2. RESULTS: LAD, LA mass, V max, V min, and V pre-A were significantly higher in
      HCM than controls. TA-SV and TA-EF were comparable in both HCM subgroups and
      controls. AA-SV and LA-KE were significantly higher in both HCM subgroups than
      controls. LA-KE was significantly higher in obstructive HCM than non-obstructive
      (P < 0.001). PA-EF and AEI were significantly lower in obstructive HCM than
      controls (P < 0.05). CONCLUSION: HCM is associated with increased LA size and
      augmented LA pump function especially obstructive type. LA conduit and reservoir
      functions are impaired in obstructive HCM.

PMID- 17541728
TI  - Molecular cloning and characterization of Hearm caspase-1 from Helicoverpa
      armigera.
AB  - Members of the caspase family play a central and evolutionary role in programmed
      cell death (PCD), which removes unwanted, damaged and dangerous cells during
      development to maintain homeostasis. In this paper, we describe the cloning and
      characterization of a caspase from the cotton bollworm, Helicoverpa armigera,
      named Hearm caspase-1. The 1,350 bp full-length cDNA contains an 885 bp open
      reading frame (ORF) that encodes a Hearm caspase-1 proenzyme of 294 amino acids.
      The deduced protein is highly homologous to Spodoptera frugiperda Sf caspase-1
      and Drosophila melanogaster ICE and has the highly conserved pentapeptide QACQG,
      the recognized catalytic site of caspases, suggesting that it is an effector
      caspase of the cotton bollworm. Northern blot and RT-PCR analyses demonstrate
      that Hearm caspase-1 is expressed in embryos and the fat body, midgut and
      haemocytes of feeding and wandering larvae. Expression of Hearm caspase-1 in the
      haemocytes appears to be correlated with the pulse of ecdysone, and it is up
      regulated by ecdysone agonist RH-2485, implying that Hearm caspase-1 activation
      is regulated by ecdysone.

PMID- 17541729
TI  - Against happiness.

PMID- 17541730
TI  - An automated high-throughput screening method for the identification of high
      yield, soluble protein variants using cell-free expression and systematic
      truncation.
AB  - A highly automated method for rapidly identifying soluble protein variants with
      good expression yields has been developed. This method is based on a commercially
      available in vitro protein expression system. It consists of two polymerase chain
      reactions (PCR) followed by in vitro protein expression and protein
      quantification by dot blot. The PCR protocols have been improved and optimized to
      allow automation using commercial fluid handling devices. A PCR primer design
      program has also been implemented to streamline protein variant design. This
      automated protocol is highly reliable and has tremendously improved the
      throughput of expression screening as compared to conventional cell-based methods
      and manual in vitro methods. We have applied this method to 32 problematic
      targets from the TB Structural Genomics Consortium. Experimental results of these
      studies are reported.

PMID- 17541731
TI  - Influence of cryopreservation on human periodontal ligament cells in vitro.
AB  - Cryopreservation of teeth before autotransplantation may create new possibilities
      in dentistry. The purpose of this study was to examine the effect of a
      standardised cryopreservation procedure on human periodontal ligament (PDL) cell
      cultures. Human PDL fibroblasts obtained from immature third molars of 11
      patients were cultured and divided into two groups. The experimental group was
      cryopreserved and cultured after thawing. The control group was cultured without
      cryopreservation. A comparison was made between cryopreserved and control cells.
      To evaluate possible differences in the characteristics of the fibroblasts, the
      cells in both groups were tested for viability (membrane integrity), growth
      capacity and alkaline phosphatase (ALP) expression. The Wilcoxon test for paired
      comparison between cryopreserved and non-cryopreserved cells was performed for
      each characteristic. The results showed that membrane integrity of cells was not
      influenced by cryopreservation. There was no statistically significant difference
      in growth capacity between cryopreserved and control cells. Non-cryopreserved
      cells were slightly stronger positive for ALP, but the difference was not
      statistically significant. From these experiments it can be concluded that the
      observed parameters are not influenced by cryopreservation.

PMID- 17541732
TI  - The polymorphism of indomethacin: an analysis by density functional theory
      calculations.
AB  - PURPOSE: Indomethacin exhibits conformational polymorphism. Crystal structures of
      two polymorphs have been solved bearing different molecular conformations.
      Herein, the conformational variance in the crystals was examined by density
      functional theory (DFT) calculations in order to understand the mutual influence
      between electronic structures and crystal packing. METHODS: Electronic structures
      of the two polymorphs and the single molecule of indomethacin were calculated
      with quantum mechanical methods. Electronic properties based upon conceptual
      density functional theory were thereby analyzed. A potential energy surface was
      generated with regard to the conformational flexibility, which was identified by
      the electronic analysis. Lattice energies of the two polymorphs were further
      calculated with an empirically augmented DFT method. RESULTS: Electronic
      properties, including electronic and nuclear Fukui functions, provided a
      fundamental understanding of the energetic competition in the indomethacin
      molecule between delocalization of p-orbitals of two aromatic rings and steric
      repulsions. Two dihedral angles (the tau1 and tau2 in Fig. 1) were found playing
      a crucial role in affecting such competition and determining the variation of
      molecular conformations. The existing polymorphs, alpha- and gamma-forms, were
      located in local minima on the energy surface based on the two dihedral angles of
      their molecular conformations. Calculated lattice energies suggest the alpha-form
      is more stable than the gamma-form at the zero K. CONCLUSIONS: The polymorphism
      of indomethacin lies in various meta-stable conformations of the molecule that
      are results of different orientations between the two aromatic indole and phenyl
      rings. The analysis of electronic and nuclear Fukui functions permits the
      revelation of local energy barriers that determine the conformational diversity
      and, for the case of indomethacin, the conformational polymorphism.

PMID- 17541733
TI  - Cytosolic delivery of liposomally targeted proteins induced by photochemical
      internalization.
AB  - PURPOSE: The application of therapeutic proteins is often hampered by limited
      cell entrance and lysosomal degradation, as intracellular targets are not
      reached. By encapsulation of proteins into targeted liposomes, cellular uptake
      via endocytosis can be enhanced. To prevent subsequent lysosomal degradation and
      promote endosomal escape, photochemical internalization (PCI) was studied here as
      a tool to enhance endosomal escape. PCI makes use of photosensitising agents
      which localize in endocytic vesicles, inducing endosomal release upon light
      exposure. MATERIALS AND METHODS: The cytotoxic protein saporin was encapsulated
      in different types of targeted liposomes. Human ovarian carcinoma cells were
      incubated with the photosensitiser TPPS2a and liposomes. To achieve photochemical
      internalization, the cells were illuminated for various time periods. Cell
      viability was used as read-out. Illumination time and amount of encapsulated
      proteins were varied to investigate the influence of these parameters. RESULTS:
      The cytotoxic effect of liposomally targeted saporin was enhanced by applying
      PCI, likely due to enhanced endosomal escape. The cytotoxic effect was dependent
      on the amount of encapsulated saporin and the illumination time. CONCLUSION: PCI
      is a promising technique for promoting cytosolic delivery of liposomally targeted
      saporin. PCI may also be applicable to other liposomally targeted therapeutic
      proteins with intracellular targets.

PMID- 17541734
TI  - Allometric scaling of pharmacodynamic responses: application to 5-Ht1A receptor
      mediated responses from rat to man.
AB  - PURPOSE: The aim of the present study was to assess whether two widely used
      biomarkers for 5-HT(1A)-receptor mediated responses in the rat (hypothermia and
      corticosterone increase) could be scaled to man using allometric principles.
      MATERIALS AND METHODS: Mechanism-based pharmacokinetic-pharmacodynamic (PK-PD)
      models were developed and characterized in rats for the standard 5-HT(1A)
      receptor agonists, buspirone and flesinoxan. Allometric scaling was investigated
      on the basis of simulation taking into account the inter-individual variability
      and clinical study design. The model-predicted effects of both flesinoxan and
      buspirone were compared to those published in the literature. RESULTS: The main
      finding of this analysis was that for both hypothermia and cortisol increase, the
      model could predict the extent of the pharmacological response in man adequately.
      For the hypothermic response, the time course of the response was also predicted
      with a high degree of accuracy. In contrast, in the case of the cortisol
      response, the observed time lag was, despite the fact that it fell within the
      model uncertainty, not predicted. CONCLUSIONS: Based on these analyses, it is
      concluded that allometrically scaled mechanism based PK-PD models are promising
      as a means of predicting the pharmacodynamic responses in man. This approach
      provides for a novel way of interpreting and scaling pre-clinical pharmacological
      responses and ultimately facilitates the understanding and prediction of
      pharmacological responses in man.

PMID- 17541735
TI  - A protective allergy vaccine based on CpG- and protamine-containing PLGA
      microparticles.
AB  - PURPOSE: Allergen-specific immunotherapy (SIT) requires dozens of subcutaneous
      injections over 3 to 5 years in order to control IgE-mediated hypersensitivity,
      which is a T-helper 2 (Th2)-associated pathology. This study investigates the use
      of poly(lactide-co-glycolide) (PLGA) microparticles combined with
      immunostimulatory oligodeoxynucleotide (CpG), as well as protamine in SIT.
      MATERIALS AND METHODS: We prepared microparticle formulations with the major
      allergen of bee venom, phospholipase A2 (PLA2), and analyzed the effect of co
      encapsulated or admixed CpG in both naive and bee venom allergic mice. RESULTS:
      Mice immunized with microparticles containing only PLA2 induced weak antibody
      responses. In contrast, the combination with CpG resulted in strong PLA2-specific
      antibody responses. The presence of CpG was required for the induction of the Th1
      associated isotype IgG2a, and the titers of IgG2a in sensitized mice correlated
      with a better protection against an allergen challenge. The effect of CpG was
      further strengthened when protamine was co-encapsulated for complexation of CpG.
      CONCLUSIONS: This study shows that allergen-specific immunotherapy with a PLGA
      based allergen-delivery system in combination with CpG enhanced the induction of
      protective IgG2a immune responses. This may improve SIT compliance and shorten
      its duration.

PMID- 17541736
TI  - Myocardial ischaemia-reperfusion injury is attenuated by intact glucagon like
      peptide-1 (GLP-1) in the in vitro rat heart and may involve the p70s6K pathway.
AB  - BACKGROUND AND METHODS: Glucagon Like Peptide-1 (GLP-1), one of the most potent
      incretin hormones, has potential beneficial actions on the ischaemic and failing
      heart. This study sought to further identify the mechanisms of action of GLP-1 on
      the ischaemic heart using an in vitro isolated perfused rat heart model of
      ischaemic-reperfusion injury (measuring infarct size to area of risk (%))
      subjected to 35 min regional ischaemia and 2 h reperfusion. To examine the effect
      of intact GLP-1 we used an inhibitor of GLP-1 breakdown, Valine pyrrolidide (VP).
      The downstream target of phosphatidylinositol 3-kinase includes the mTOR/p70s6
      kinase pathway which was pharmacologically inhibited by rapamycin. RESULTS AND
      CONCLUSION: GLP-1 alone did not decrease myocardial infarction (54.4 +/- 3.1%).
      VP alone did not decrease myocardial infarction (52.5 +/- 4%). GLP-1 in the
      presence of VP produced significant reduction in myocardial infarction compared
      to control hearts (28.4 +/- 2.7% vs. 56.4 +/- 3.9% vs. P < 0.05). Inhibiting
      p70s6 Kinase with rapamycin completely abolished GLP-1 induced protection (57.1
      +/- 4.9% vs. 28.4 +/- 2.7% P < 0.05). There was no detectable increase in the
      phosphorylated p70s6k after either 5 or 10 min of treatment with GLP-1/VP or with
      VP alone in comparison to control blots. In conclusion we show for the first time
      that the protective effects of GLP-1 are mediated by intact GLP-1 and can be
      inhibited by blocking the p70s6 kinase.

PMID- 17541737
TI  - The familial clustering of age at menarche in extended twin families.
AB  - The timing of puberty is complex, possibly involving many genetic factors that
      may interact with environmental influences. Familial resemblance for age at
      menarche was studied in a sample of 4,995 female twins, 1,296 sisters, 2,946
      mothers and 635 female spouses of male twins. They had indicated their age at
      menarche as part of a larger longitudinal survey. We assessed assortative mating
      for age at menarche, gene-environment interaction effects and estimated the
      heritability of individual differences in pubertal timing. There was significant
      evidence of gene-environment interaction, accounting for 1.5% of the variance.
      There was no indication of consistent mate assortment on age at menarche.
      Individual differences in age at menarche are highly heritable, with additive
      genetic factors explaining at least 70% of the true variation. An additional 1.5%
      of the variation can be explained by a genotype-environment interaction effect
      where environmental factors are more important in individuals genetically
      predisposed for late menarche.

PMID- 17541738
TI  - Neuropathology of mitochondrial diseases.
AB  - The term "mitochondrial diseases" (MD) refers to a group of disorders related to
      respiratory chain dysfunction. Clinical features are usually extremely
      heterogeneous because MD may involve several tissues with different degrees of
      severity. Muscle and brain are mostly affected, probably because of their high
      dependence on oxidative metabolism. Muscle can be the only affected tissue or
      involved as a part of a multi-system disease; ragged red fibers, accumulation of
      structurally altered mitochondria and cytochrome-c-oxidase (COX) negative fibers
      are the main pathological features. In mitochondrial encephalopathies, central
      nervous system (CNS) structures are affected according to different patterns of
      distribution and severity. Characteristic lesions are neuronal loss, vasculo
      necrotic changes, gliosis, demyelination and spongy degeneration. In accordance
      with either grey matter or white matter involvement two main groups of diseases
      may be distinguished. Neuronal loss and vasculo-necrotic multifocal lesions are
      the common features of grey matter involvement; demyelination and spongy
      degeneration occur when white matter is affected, often associated with less
      severe lesions of the grey structures. Grey matter lesions are prevalent in
      MERRF, MELAS, Alpers and Leigh syndromes. White matter involvement is always seen
      in Kearns-Sayre syndrome and was recently described in mtDNA depletion syndrome
      linked to dGK mutations and in the rare conditions associated with complex I and
      II deficiency. In this review we describe the main histopathological features of
      muscle and CNS lesions in mitochondrial diseases.

PMID- 17541739
TI  - Melatonin, environmental light, and breast cancer.
AB  - Although many factors have been suggested as causes for breast cancer, the
      increased incidence of the disease seen in women working in night shifts led to
      the hypothesis that the suppression of melatonin by light or melatonin deficiency
      plays a major role in cancer development. Studies on the 7,12
      dimethylbenz[a]anthracene and N-methyl-N-nitrosourea experimental models of human
      breast cancer indicate that melatonin is effective in reducing cancer
      development. In vitro studies in MCF-7 human breast cancer cell line have shown
      that melatonin exerts its anticarcinogenic actions through a variety of
      mechanisms, and that it is most effective in estrogen receptor (ER) alpha
      positive breast cancer cells. Melatonin suppresses ER gene, modulates several
      estrogen dependent regulatory proteins and pro-oncogenes, inhibits cell
      proliferation, and impairs the metastatic capacity of MCF-7 human breast cancer
      cells. The anticarcinogenic action on MCF-7 cells has been demonstrated at the
      physiological concentrations of melatonin attained at night, suggesting thereby
      that melatonin acts like an endogenous antiestrogen. Melatonin also decreases the
      formation of estrogens from androgens via aromatase inhibition. Circulating
      melatonin levels are abnormally low in ER-positive breast cancer patients thereby
      supporting the melatonin hypothesis for breast cancer in shift working women. It
      has been postulated that enhanced endogenous melatonin secretion is responsible
      for the beneficial effects of meditation as a form of psychosocial intervention
      that helps breast cancer patients.

PMID- 17541740
TI  - Quantitative analysis of mitochondrial DNA 4977-bp deletion in sporadic breast
      cancer and benign breast diseases.
AB  - The mitochondrial DNA (mtDNA) 4977-bp deletion (DeltamtDNA(4977) mutation) is one
      of the most frequently observed mtDNA mutations in human tissues and may play a
      role in carcinogenesis. Only a few studies have evaluated DeltamtDNA(4977)
      mutation in breast cancer tissue, and the findings have been inconsistent, which
      may be due to methodological differences. In this study, we developed a
      quantitative real-time PCR assay to assess the level of the DeltamtDNA(4977)
      mutation in tumor tissue samples from 55 primary breast cancer patients and 21
      patients with benign breast disease (BBD). The DeltamtDNA(4977) mutation was
      detected in all of the samples with levels varying from 0.000149% to 7.0%. The
      DeltamtDNA(4977) mutation levels were lower in tumor tissues than in adjacent
      normal tissues in both breast cancer and BBD subjects. The differences, however,
      were not statistically significant. No significant difference between breast
      cancer and BBD patients was found in the DeltamtDNA(4977) mutation levels of
      tumor tissues and adjacent normal tissues. The DeltamtDNA(4977) mutation levels
      were not significantly associated with clinicopathological characteristics (age,
      histology, tumor stage, and ER/PR status) in breast cancer or BBD patients. These
      results do not support the notion that the mitochondrial DNA 4977-bp deletion
      plays a major role in breast carcinogenesis.

PMID- 17541741
TI  - Tamoxifen, hot flashes and recurrence in breast cancer.
AB  - We utilized data from the comparison group of the Women's Healthy Eating and
      Living randomized trial to investigate an "a priori" hypothesis suggested by
      CYP2D6 studies that hot flashes may be an independent predictor of tamoxifen
      efficacy. A total of 1551 women with early stage breast cancer were enrolled and
      randomized to the comparison group of the WHEL multi-institutional trial between
      1995 and 2000. Their primary breast cancer diagnoses were between 1991 and 2000.
      At study entry, 864 (56%) of these women were taking tamoxifen, and hot flashes
      were reported by 674 (78%). After 7.3 years of follow-up, 127 of those who took
      tamoxifen at baseline had a confirmed breast cancer recurrence. Women who
      reported hot flashes at baseline were less likely to develop recurrent breast
      cancer than those who did not report hot flashes (12.9% vs 21%, P = 0.01). Hot
      flashes were a stronger predictor of breast cancer specific outcome than age,
      hormone receptor status, or even the difference in the stage of the cancer at
      diagnosis (Stage I versus Stage II). These findings suggest an association
      between side effects, efficacy, and tamoxifen metabolism. The strength of this
      finding suggests that further study of the relationship between hot flashes and
      breast cancer progression is warranted. Additional work is warranted to clarify
      the mechanism of hot flashes in this setting.

PMID- 17541742
TI  - Germline TP53 mutations in BRCA1 and BRCA2 mutation-negative French Canadian
      breast cancer families.
AB  - About 40% of French Canadian breast and/or ovarian cancer families harbor
      germline BRCA1 or BRCA1 mutations where common mutations account for about 84% of
      all mutations identified in cancer families. Within a series of BRCA1 and BRCA2
      mutation-negative families, a germline TP53 13398 G>A (Arg213Gln) mutation was
      identified, which was selected for mutation analysis in this gene because of a
      family history consistent with Li-Fraumeni syndrome (LFS). Given the founder
      effects in this population, the 13398 G>A mutation was screened in series of 52
      BRCA1 and BRCA2 mutation-negative cancer families, and a mutation-positive family
      was identified. However, pedigree inspection and expansion of mutation-positive
      families with the same mutation revealed that they were closely related to each
      other. To further characterize the contribution of TP53 in cancer families,
      mutation analysis was performed in the remaining BRCA1 and BRCA2 mutation
      negative cancer families. Thirty sequence variants were identified, the majority
      of which occur in intronic sequences and are not predicted to affect the
      functionality of TP53. However, the 14538 G>A (Arg290His) mutation was identified
      in a family which did not exhibit features consistent with LFS or Li-Fraumeni
      like (LFL) syndrome. Neither of the TP53 mutations was detected in 381 French
      Canadian women with breast cancer diagnosed before 50 years of age not selected
      for family history of cancer. In all, germline TP53 mutations were identified in
      two of 52 (3.8%) cancer families, suggesting that TP53 is not a major contributor
      to BRCA1 and BRCA2 mutation-negative breast and/or ovarian cancer families of
      French Canadian descent.

PMID- 17541743
TI  - Shortage of lipid-radical cycles in membranes as a possible prime cause of
      energetic failure in aging and Alzheimer disease.
AB  - Polyunsaturated fatty acids (PUFA) and alpha-tocopherol (alpha-TOH) are the most
      oxygen-sensitive constituents of cells. alpha-TOH is a member of the vitamin E
      family that is considered the most important lipophilic antioxidant in cell
      membranes. Its importance is emphasized by the involvement of oxidative stress in
      injury to the central nervous system and neurodegenerative diseases. Currently,
      alpha-TOH transfer protein (TTP), is believed to play a significant role in
      maintaining the vitamin status but the presence of alpha-TOH in membranes is
      required but not sufficient to protect the membranes against lipid hydroperoxides
      (LOOH) formation. The lipid-radical theory presented in this review considers the
      role of two membrane factors--alpha-tocopherol and cytochrome b5; these factors
      secure the functioning of lipid-radical cycles and the participation of lipid
      radical reactions in the key membrane processes. The prominent intermembrane
      reaction realized via a protein-lipid interaction, during which electron
      transport from cytochrome b5--located in the outer membrane--to peroxyl radical
      (LOO*)--located in inner membrane--causes reduction of the peroxyl radical:
      cyt.b5red + LOO* --> cyt.b5ox + LOO(-). This secures an interaction of alpha-TOH
      with other intermediate, LOO(- )excepting the LOOH formation. The discussion will
      be focused on the consequences of ineffective electron transfer to LOO* and
      excessive oxidative pathway of metabolism of the PUFA (LOO* --> LOOH). Assuming
      the operation of cytochrome b5/alpha-tocopherol-controlled lipid-radical cycles
      and considering the role of the cycles in membrane bioenergetics we arrive at a
      model for effective function of adenine nucleotide translocator and ATP synthesis
      in mitochondria. This paper summarizes our experimental evidence that the
      oxidative and non-oxidative pathways of metabolism of PUFA via their respective
      intermediates occur in the cells. While this fact is not widely appreciated it
      may be relevant to elucidation of new mechanisms of neurodegenerative diseases.

PMID- 17541744
TI  - An application of the rational choice approach to the offending process of sex
      offenders: a closer look at the decision-making.
AB  - Although the study of both offense processes and implicit theories provides in
      depth knowledge about the decision-making of sex offenders, these studies focus
      solely on the internal psychological processes of the offender leading to the
      commission of a sexual assault. These studies neglect to look specifically at the
      offender's decision-making during the offense in interaction with the immediate
      situations encountered at the offense scene, such as the choices of behavior
      while interacting with the victim in a specific context. Based on a rational
      choice approach, this study investigates the decision-making involved in the
      offending process of 69 serial sexual offenders who have committed their crimes
      against stranger victims. Semi-structured interviews were conducted with
      offenders in order to identify the rationale behind their actions during the pre
      crime phase (premeditation of the crime, estimation of risk of apprehension by
      the offender, and forensic awareness of the offender), crime phase (use of a
      weapon, use of restraints, use of a vehicle, and level of force used), and the
      post-crime phase (event leading to the end of crime and victim release site
      location choice). Results show that sex offenders, even if traditionally
      described as "irrational" and impulsive individuals, are capable, up to a certain
      point, of an analysis of the costs/benefits related to their actions. Moreover,
      results emphasize the important role of situational factors, such as victim
      resistance, on the decision-making process of sex offenders. Implications of the
      results are briefly discussed in regard of clinical practice and crime
      prevention.

PMID- 17541745
TI  - Preventing homelessness among substance users in Europe.
AB  - Prior to the 1970s, neither homelessness nor drug addiction was seen as issues of
      major concern in Europe. At most, they were of local interest and of particular
      importance only in some larger metropolitan centres. Over the last three decades
      they have come much more into public prominence and risen up in local and
      national policy agendas. At the level of the European Union (EU), however, while
      the use and abuse of drugs has attracted substantial financial resources and
      institutional involvement, homelessness, in comparison, has been relatively
      neglected and remains predominantly the concern of non-government and voluntary
      organisations. At all three levels-local, national, and European-it is only in
      recent years that the link between homelessness and problematic substance use has
      come to the fore as an issue of singular concern. This paper examines the recent
      emergence of policies and programmes which seek to tackle and prevent
      homelessness among substance users. Our investigation suggests that although new
      initiatives at the EU level are limited, at the national and especially sub
      national level, effective programmes addressing both treatment and prevention are
      being designed and implemented.

PMID- 17541746
TI  - An electroporation microchip system for the transfection of zebrafish embryos
      using quantum dots and GFP genes for evaluation.
AB  - This study focuses on the design and experimental verification of an
      electroporation (EP) microchip system for the transfection of zebrafish (Danio
      rerio). For generating suitable pulses, a circuit is used to provide voltages
      between 0 and 700 V, with nearly 0-3,500 V/cm electric field. In addition, a
      proposed EP microchip, designed in a modular fashion, is fabricated using micro
      electromechanical system (MEMS) technology to allow for rapid and convenient
      replacement of each component. A numerical simulation is carried out to analyze
      the uniformity and strength of the EP electric fields generated in the microchip.
      Trypan blue dye, water-soluble quantum dots (MUA-QDs) and genes coding for green
      fluorescence protein (pEGFP-N1 plasmids) were employed to verify the successful
      delivery and transfection of zebrafish embryos. The experimental results show
      that the optimum delivery rate of trypan blue dyes and MUA-QDs were respectively
      up to 62 and 36% by using the proposed EP system. The successfully transfected
      embryos with the pEGFP-N1 plasmid used exhibit green fluorescence in the
      zebrafish embryos. The approach in the transfection of zebrafish embryos will
      provide many potential usages for cellular imaging areas, gene therapy research
      and medical applications.

PMID- 17541747
TI  - Cell loss in integrated microfluidic device.
AB  - Cell loss during sample transporting from macro-components to micro-components in
      integrated microfluidic devices can considerably deteriorate cell detection
      sensitivity. This intrinsic cell loss was studied and effectively minimized
      through (a) increasing the tubing diameter connecting the sample storage and the
      micro-device, (b) applying a hydrodynamic focusing approach for sample delivering
      to reduce cells contacting and adhesion on the walls of micro-channel and chip
      inlet; (c) optimizing the filter design with a zigzag arrangement of pillars (13
      microm in chamber depth and 0.8 microm in gap) to prolong the effective filter
      length, and iv) the use of diamond shaped pillar instead of normally used
      rectangular shape to reduce the gap length between any two given pillar (i.e.
      pressure drop) at the filter region. Cell trapping and immunofluorescent
      detection of 12 Giardia lamblia and 12 Cryptosporidium parvum cells in 150 microl
      solution and 50 MCF-7 breast cancer cells in 150 microl solution was completed
      within 15 min with trapping efficiencies improved from 79+/-11%, 50.8+/-5.5% and
      41.3+/-3.6% without hydrodynamic focusing, respectively, to 90.8+/-5.8%, 89.8+/
      16.6% and 77.0+/-9.2% with hydrodynamic focusing.

PMID- 17541748
TI  - Symptomatic pituitary metastases from renal cell carcinoma.
AB  - Symptomatic metastases to the pituitary (MP) from renal cell carcinoma (RCC) are
      rare. In this largest case series reported, we describe the clinical features,
      treatment and outcome of 5 patients. Over a 6-year period (2000-2006), we treated
      5 patients (3 males; mean age 61 years) with large sellar masses and RCC. Four
      patients had a history of RCC, while in one, RCC was diagnosed after surgery. RCC
      was diagnosed a median of 11 years prior to diagnosis of MP (range 0-27 years).
      Four patients had previously developed distant metastases. Clinical presentation
      included bitemporal hemianopia (3 patients), lethargy (3), headaches (2) and
      diabetes insipidus (DI) (2). Panhypopituitarism was present in 3 patients and the
      other two had deficiency of at least ACTH and gonadotropin axes. Elevated
      prolactin was seen in 3 patients. MRI showed an enhancing sellar mass with
      suprasellar extension and chiasmal compression in all; prominent vascular flow
      voids were seen in 2. Three patients underwent transsphenoidal surgery and
      radiation, while 2 underwent radiotherapy alone. Four patients are alive (follow
      up 6-46 months); 1 patient died due to systemic metastases at 12 months.
      Metastases to the pituitary from RCC cause more severe hypopituitarism and visual
      dysfunction compared to those from other primaries, whereas DI is less common.
      MRI shows contrast enhancement, stalk involvement, sclerosis and/or erosion of
      sella and presence of vascular flow voids. Combined treatment using decompressive
      surgery and stereotactic radiotherapy may result in better outcomes.

PMID- 17541749
TI  - Acromegaly caused by growth hormone-releasing hormone-producing tumors: long-term
      observational studies in three patients.
AB  - We report on three newly diagnosed patients with extracranial ectopic GHRH
      associated acromegaly with long-term follow-up after surgery of the primary
      tumor. One patient with a pancreatic tumor and two parathyroid adenomas was the
      index case of a large kindred of MEN-I syndrome. The other two patients had a
      large bronchial carcinoid. The first patient is still in remission now almost 22
      years after surgery. In the two other patients GHRH did not normalize completely
      after surgery and they are now treated with slow-release octreotide. IGF-I
      normalized in all patients. During medical treatment basal GH secretion remained
      (slightly) elevated and secretory regularity was decreased in 24 h blood sampling
      studies. We did not observe development of tachyphylaxis towards the drug or
      radiological evidence of (growing) metastases. We propose life-long suppressive
      therapy with somatostatin analogs in cases with persisting elevated serum GHRH
      concentrations after removal of the primary tumor. Independent parameters of
      residual disease are elevated basal (nonpulsatile) GH secretion and decreased GH
      secretory regularity.

PMID- 17541750
TI  - Mechanism of action of octreotide in acromegalic tumours in vivo using dynamic
      contrast-enhanced magnetic resonance imaging.
AB  - CONTEXT: Octreotide causes significant tumour shrinkage in patients with
      acromegaly but the exact mechanism of action is unclear in vivo. OBJECTIVE: To
      determine the mechanism of action of octreotide in vivo using dynamic contrast
      enhanced magnetic resonance imaging (DCE-MRI). DESIGN: Five patients with
      acromegaly were treated with octreotide as primary medical therapy. DCE-MRI was
      done at baseline and 24 weeks. Local ethical committee approval was granted.
      SETTING: Study was done in a tertiary care centre. PATIENTS: Five patients with
      newly diagnosed acromegaly were recruited. INTERVENTION: Patients were started on
      subcutaneous octreotide and DCE-MRI was done on 0 and 24 weeks. MAIN OUTCOME
      MEASURES: Amplitude of contrast intake, exchange rate and maximum enhancement
      index of tumour tissue was compared before and after treatment. RESULTS:
      Amplitude of contrast intake (9.87 +/- 3.52 vs. 4.97 +/- 1.96 P < or = 0.05) and
      exchange rate (6.27 +/- 1.57 vs. 1.63 +/- 0.76 P value < or = 0.01) were
      significantly higher at baseline in adenoma compared to normal pituitary tissue
      but was comparable to normal pituitary tissue after treatment. There was a
      significant decrease in amplitude of contrast intake and exchange rate which
      relates to functional vascularity of adenoma at 24 weeks compared to baseline (P
      values 0.026 and 0.002 respectively) but there were no significant changes in the
      normal pituitary tissue. CONCLUSION: DCE-MRI in acromegalic tumours treated with
      octreotide showed a significant reduction in functional vascularity after
      octreotide therapy compared to baseline in pituitary adenomas. This supports the
      antiangiogenic action of somatostatin analogue therapy in vitro, but it remains
      unclear if this mechanism is important clinically in analogue pre-treatment
      reducing the effect of radiotherapy on these pituitary tumours.

PMID- 17541751
TI  - Regulation of excitation by glycine receptors.
AB  - Our knowledge of glycine receptor (GlyR) regulation of excitation has advanced
      significantly in recent years. GlyRs are widespread in the CNS, are
      heterogeneous, and undergo developmental changes. Activation of GlyRs of immature
      neurons induces outflow of Cl( - ), membrane depolarization, neuronal excitation,
      calcium influx, and transmitter release, in contrast to the inhibitory effects
      these receptors have in mature neurons. Thus, GlyRs are important for neuronal
      excitability in both the developing and the mature CNS. This chapter is an
      overview of selective studies on the newly discovered roles of GlyRs in
      regulating neuronal excitation, and inhibition, particularly in the upper brain
      areas.

PMID- 17541752
TI  - Evidence-based guidelines for the prevention of ventilator-associated pneumonia:
      results of a knowledge test among intensive care nurses.
AB  - OBJECTIVE: To determine intensive care nurses' knowledge of evidence-based
      guidelines for the prevention of ventilator-associated pneumonia (VAP). DESIGN: A
      survey using a validated multiple-choice questionnaire, developed to evaluate
      nurses' knowledge of VAP prevention. The questionnaire was distributed and
      collected during the annual congress of the Flemish Society for Critical Care
      Nurses (Ghent, November 2005). Demographic data included were gender, years of
      intensive care experience, number of critical beds, and whether respondents hold
      a special degree in emergency and intensive care. MAIN RESULTS: We collected 638
      questionnaires (response rate 74.6%). Nineteen percent of the respondents
      recognized the oral route as the recommended way for intubation. It was known by
      49% of respondents that ventilator circuits should be changed for each new
      patient. Heat and moisture exchangers were checked as the recommended type of
      humidifier by 55% of respondents, but only 13% knew that it is recommended to
      change them once weekly. Closed suctioning systems were identified as recommended
      by 17% of respondents, and 20% knew that these must be changed for each new
      patient only. Sixty percent and 49%, respectively, recognized subglottic drainage
      and kinetic beds to reduce the incidence of VAP. Semi-recumbent positioning is
      well known to prevent VAP (90%). The average knowledge level was higher among
      more experienced nurses (> 1 year experience) and those holding a special degree
      in emergency and intensive care. CONCLUSION: Nurses lack knowledge regarding
      recommendations for VAP prevention. Nurses' schooling and continuing education
      should include support from current evidence-based guidelines.

PMID- 17541753
TI  - Tension-free vaginal tape: what it's made of can matter!
AB  - Urinary stress incontinence is a significant health concern affecting millions of
      women and is due to poor anatomical support of the urethra. Sub-urethral tapes
      aim to correct this lack of support to achieve continence. The simplicity and
      success rates of the tension-free vaginal tape (TVT) technique compare favourably
      with Burch colposuspension. The last 13 years have seen the introduction of new
      materials and approaches used for sub-urethral tapes to optimise the efficacy and
      reduce the complications of the procedure. We present a case series using a tape
      made of siliconised polyester (LIFT, Cousin(R)). Approximately half of the cases
      have presented with an array of symptoms suggestive of an intense inflammatory
      response, which resolved only on removal of the tape. A low yield on
      microbiological samples was evident. We suggest that the material is as important
      as the weave in deciding which mesh to use.

PMID- 17541754
TI  - Molecular and functional properties of the psychrophilic elongation factor G from
      the Antarctic Eubacterium Pseudoalteromonas haloplanktis TAC 125.
AB  - The molecular and functional properties of the elongation factor (EF) G from the
      psychrophilic Antarctic eubacterium Pseudoalteromonas haloplanktis (Ph) were
      studied. PhEF-G catalyzed protein synthesis in vitro that was inhibited by
      fusidic acid, an antibiotic specifically acting on EF-G. The EF interacted with
      GDP only in the presence of P. haloplanktis ribosome and fusidic acid with an
      affinity similar to that displayed by Escherichia coli EF-G. The psychrophilic
      translocase elicited a ribosome-dependent GTPase that was competitively inhibited
      by GDP, the slowly hydrolyzable GTP analog GppNHp, and the protein synthesis
      inhibitor ppGDP. The temperature dependence of the activity of PhEF-G reached its
      maximum at least 26 degrees C beyond the growth temperature of P. haloplanktis (4
      20 degrees C). The heat inactivation profile of the ribosome-dependent GTPase of
      PhEF-G gave a temperature for half inactivation (46 degrees C), significantly
      lower than that for half denaturation measured by either UV- (57 degrees C) or
      fluorescence-melting (62 degrees C). This finding was attributed to a different
      effect of the temperature on the catalytic domain with respect to that elicited
      on the other domains constituting the EF, thus confirming the differential
      molecular flexibility present in psychrophilic enzymes. A molecular model, based
      on the 3D coordinates of a thermophilic EF-G, showed differences only in
      connecting loops.

PMID- 17541755
TI  - Memory effect in isothermal crystallization of syndiotactic polypropylene - role
      of melt structure and dynamics?
AB  - The crystalline-memory effect on the crystallization of syndiotactic
      polypropylene is investigated by differential scanning calorimetry and solid
      state NMR spectroscopy. The influence of several parameters in the thermal (pre
      )treatment and the crystallization conditions is studied in detail. In agreement
      with previous reports, the power law behavior of the overall crystal growth rate
      is found to be remarkably different for melts with and without memory. This has
      previously been interpreted in terms of changes in the structure and/or the
      dynamics of the melt (disentangled state, local order), and a variety of NMR
      experiments is used to detect such potential changes. All our NMR results are
      identical for melts with and without memory, therefore excluding any large effect
      of the "memory" on melt structure or dynamics exceeding the percent level of the
      whole sample volume, and thus supporting more conventional interpretations in
      terms of persisting nuclei. Samples that were pre-crystallized at lower
      temperatures exhibit a larger memory effect, and the potential nuclei fraction is
      a non-equilibrium structure and is restricted to the 0.1% level if it is
      crystalline or highly ordered.

PMID- 17541756
TI  - Complete wetting of pits and grooves.
AB  - For one-component volatile fluids governed by dispersion forces an effective
      interface Hamiltonian, derived from a microscopic density functional theory, is
      used to study complete wetting of geometrically structured substrates. Also the
      long range of substrate potentials is explicitly taken into account. Four types
      of geometrical patterns are considered: i) one-dimensional periodic arrays of
      rectangular or parabolic grooves and ii) two-dimensional lattices of cylindrical
      or parabolic pits. We present numerical evidence that at the centers of the
      cavity regions the thicknesses of the adsorbed films obey precisely the same
      geometrical covariance relation, which has been recently reported for complete
      cone and wedge filling. However, this covariance does not hold for the laterally
      averaged wetting film thicknesses. For sufficiently deep cavities with vertical
      walls and close to liquid-gas phase coexistence in the bulk, the film thicknesses
      exhibit an effective planar scaling regime, which as a function of
      undersaturation is characterized by a power law with the common critical exponent
      -1/3 as for a flat substrate, but with the amplitude depending on the geometrical
      features.

PMID- 17541757
TI  - Fluctuation spectra of free and supported membrane pairs.
AB  - Fluctuation spectra of fluid compound membrane systems are calculated. The
      systems addressed contain two (or more) almost parallel membranes that are
      connected by harmonic tethers or by a continuous, harmonic confining potential.
      Additionally, such a compound system can be attached to a supporting substrate.
      We compare quasi-analytical results for tethers with analytical results for
      corresponding continuous models and investigate under what circumstances the
      discrete nature of the tethers actually influences the fluctuations. A tethered,
      supported membrane pair with similar bending rigidities and stiff tethers can
      possess a nonmonotonic fluctuation spectrum with a maximum. A nonmonotonic
      spectrum with a maximum and a minimum can occur for an either free or supported
      membrane pair of rather different bending rigidities and for stiff tethers.
      Typical membrane displacements are calculated for supported membrane pairs with
      discrete or continuous interacting potentials. Thereby an estimate of how close
      the constituent two membranes and the substrate typically approach each other is
      given. For a supported membrane pair with discrete or continuous interactions,
      the typical displacements of each membrane are altered with respect to a single
      supported membrane, where those of the membrane near the substrate are diminished
      and those of the membrane further away are enhanced.

PMID- 17541758
TI  - Vagal and sympathetic heart rate and blood pressure control in adult onset PHOX2B
      mutation-confirmed congenital central hypoventilation syndrome.
AB  - BACKGROUND: Children with Congenital Central Hypoventilation Syndrome (CCHS)
      typically present as newborns with alveolar hypoventilation. With the advent of
      genetic testing, parents of affected children and other unrelated adults, all
      heterozygous for the disease-defining PHOX2B polyalanine expansion mutation with
      the 20/25 genotype, are being identified in adulthood. Though children with
      PHOX2B mutation-confirmed CCHS demonstrate ANS dysregulation, including altered
      heart rate and blood pressure control, it is unknown if adults with CCHS have
      similarly affected autonomic function in blood pressure control. METHODS AND
      RESULTS: An autonomic profile of blood pressure control has been studied with
      recording of muscle sympathetic activity and spectral analysis of heart rate and
      blood pressure variability of one adult patient with alveolar hypoventilation and
      the 20/25 PHOX2B genotype. All parameters of heart rate variability were reduced.
      Cardiac baroreflex sensitivity was decreased. Sympathetic responses to Valsalva
      maneuver, hypoxemia, isometric exercise and cold pressor were blunted.
      CONCLUSION: In summary, we found a reduced cardiac baroreflex and a blunted
      sympathetic mediated response in the individual with adult-onset CCHS, possibly
      due to dysfunction in the afferent pathway. Our results confirm that PHOX2B
      affects the development of the autonomic nervous system, possibly causing absence
      of normal maturation of carotid body and visceral sensory ganglia and leading to
      autonomic dysfunction in adult-onset CCHS.

PMID- 17541759
TI  - Simple, rapid, high-purity preparation of recombinant human platelet-derived
      growth factor-BB.
AB  - Recombinant human platelet-derived growth factor-BB (rhPDGF-BB) is used to treat
      full-thickness diabetic ulcers and is being investigated for use in other chronic
      ulcers, non-healing wounds, and periodontal defects. A simple, novel method for
      expression and purification of rhPDGF-BB from Escherichia coli is now described.
      This method produces the dimeric protein in high yield (10-12 mg/g wet cell mass)
      and with a purity >95%. rhPDGF-BB was exclusively found in inclusion bodies (IBs)
      representing approx. 30% of the total cell proteins. The IBs were extracted and
      the monomer purified by RP-HPLC. The purified rhPDGF-B monomer was then refolded
      using Tris buffer and subsequently dimerized to produce biologically active
      rhPDGF-BB. This product was composed of two polypeptide chains, each approx. 12
      kDa. The final product exhibited specific activity in a fibroblast proliferation
      assay indistinguishable from that of the WHO reference standard.

PMID- 17541760
TI  - Optimization of covalent immobilization of pectinase on sodium alginate support.
AB  - Pectinase was immobilized on a sodium alginate support using glutaraldehyde and
      retained 66% activity. The optimal pH for activity shifted from 3.0 to 3.5 after
      immobilization; however, the optimum temperature remained unchanged at 40 degrees
      C. The immobilized enzyme also had a higher thermal stability and reusability
      than the free enzyme, and retained 80% of initial activity after 11 batch
      reactions.

PMID- 17541761
TI  - Determination of left ventricular filling pressure by new echocardiographic
      methods in patients with coronary artery disease.
AB  - AIM: The present study was designed to determine the reliability of the analysis
      of the time difference between onset of mitral inflow and onset of early
      diastolic mitral annulus velocity and mean systolic strain index, and comparing
      them with E/E' in the detection of increased left ventricular end-diastolic
      pressure (LVEDP) in patients with coronary artery disease. METHODS: Eighty
      patients (mean age: 57.2 +/- 11.5 years) referred for cardiac catheterization
      were studied. Patients were divided into 2 groups according to LVEDP (group 1:
      LVEDP > 20 mmHg, n = 39 patients; group 2: LVEDP < or = 20 mmHg, n = 41
      patients). From the mitral inflow, peak E velocity was calculated. With tissue
      Doppler echocardiography, early diastolic velocity (E') measured from the septal,
      lateral, inferior and lateral mitral annulus and mean value of E' and E/E' ratio
      were calculated. The time difference between onset of mitral inflow and onset of
      early diastolic mitral annulus velocity (T(E'-E)) was calculated. From the apical
      chambers, the peak systolic strain value of 16 left ventricular (LV) segments was
      measured and the mean of these 16 segments was calculated and referred to as mean
      systolic strain index. RESULTS: The patients with increased LVEDP (group 1) had a
      higher E/E' ratio (13.8 +/- 3.4 vs. 9.9 +/- 2.8, P < 0.001) and lower mean
      systolic strain index (11.8 +/- 3.4 % vs. 13.5 +/- 3.6 %, P = 0.038) than
      patients in group 2. The sensitivity of E/E' > 13.42 for identifying LVEDP > 20
      mmHg was 71%, with a specificity of 89%. The sensitivity of a mean systolic
      strain index < 10.57% for identifying LVEDP > 20 mmHg was 44%, with a specificity
      of 83%. T(E'-E )was not significantly different between the two groups.
      CONCLUSION: The decreased longitudinal function of the left ventricle is related
      to increased LVEDP. The E/E' ratio, which in recent years has been used for the
      prediction of LV filling pressures, was a better predictor for increased LVEDP
      than the mean systolic strain score index and the time difference between onset
      of mitral inflow and onset of early diastolic mitral annulus velocity in patients
      with coronary artery disease.

PMID- 17541762
TI  - Editorial. Hypertrophic Cardiomyopathy with ventricular tachycardia.

PMID- 17541763
TI  - Diagnostic value of D-dimer measurement in patients referred to the emergency
      department with suspected myocardial ischemia.
AB  - BACKGROUND: The accurate identification of patients with acute myocardial
      infarction (AMI) remains one of the most difficult challenges facing emergency
      physicians. The introduction of early and reliable biomarkers of AMI should hence
      be acknowledged, since they would increase the efficiency of the diagnostic
      process. METHODS: A total of 2,276 consecutive patients referred to the emergency
      department for clinical symptoms suggestive for AMI underwent cardiac troponin T
      (cTnT) and D-dimer testing between January and December 2006. Patients sample
      were eligible for inclusion in this investigation if they had been collected
      prior to medication or intervention and 12-24 h after the time of patient's
      arrival to the emergency department, when the diagnostic efficiency of cTnT is
      the highest. cTnT was assayed on the Elecsys 2010 and test results were
      stratified according to the decisional threshold corresponding to the lowest TnT
      concentration associated with a 10% total imprecision in the assay (>0.03
      microg/l). Plasma D-dimer was measured employing Vidas DD. RESULTS: The results
      of 741 patient's samples fulfilled the above criteria and were included in the
      study, 252 (34%) of whom had cTnT values>0.03 microg/l. The D-dimer value
      distribution (median and 95% C.I.) was significantly different in patients with
      cTnT values>0.03 microg/l than in those with cTnT values<0.03 microg/l (2,227
      microg/l, 431-10,000 microg/l versus 1,039 microg/l, 143-6,338 microg/l;
      P<0.001). The area under the receiver operating characteristic (ROC) curve, was
      0.734 (95% confidence interval: 0.715-0.753; P<0.001). At the 500 microg/l
      diagnostic threshold estimated by the ROC curve analysis, corresponding to the
      cut-off for the diagnosis of VTE, sensitivity and specificity of Vidas D-dimer
      were 95% and 27%, respectively. The positive and negative predictive values were
      estimated as 92% and 41%, respectively. In linear regression analysis, no
      significant association (r=0.090; P=0.077) was observed between D-dimer and cTnT
      in patients with cTnT levels exceeding the decisional threshold of the assay.
      CONCLUSIONS: Results of the present investigation on patients with AMI
      established by accepted diagnostic criteria (cTnT values above the decisional
      threshold of the assay associated with suggestive clinical symptoms), testify
      that D-dimer testing would not add clinically meaningful information to the sole
      determination of the cardiospecific troponins 12-24 h after patient's admission
      at the emergency department, when the cumulative data indicate that the
      diagnostic efficiency of cTnT is the highest.

PMID- 17541764
TI  - Ischemic infarction following an intra-cerebral hemorrhage in an adult sickle
      cell disease with angiographic Moyamoya.
AB  - A 43-year-old lady, known case of sickle cell disease (SCD) was admitted in
      sickle cell crises and developed a left frontal intracerebral hematoma. She
      worsened further neurologically and was found to have developed a large left
      middle cerebral artery (MCA) infarct. Angiogram showed Moyamoya pattern. The
      patient was managed conservatively with exchange transfusions and made good
      recovery. She is being maintained on monthly exchange transfusions and
      hydroxyurea. Such a presentation has been described infrequently, that too mostly
      in children. Only once, it has been reported with adult SCD. Diagnostic and
      management controversies are discussed in the light of available literature.

PMID- 17541765
TI  - Factors related to progression of middle cerebral artery stenosis determined
      using transcranial Doppler ultrasonograhy.
AB  - Atherosclerosis plays an important role in ischemic stroke. We conducted this
      prospective study to determine significant factors related to progression of
      middle cerebral artery (MCA) stenosis. We studied 103 patients with MCA stenosis
      using transcranial Doppler (TCD) and re-evaluated the TCD results at 6 months
      after the initial investigation and measured platelet aggregability for adenosine
      diphosphate (ADP) or arachidonic acid (AA). After 6 months, 13 (12.6%) patients
      showed worsening, whereas 90 were stationary or showed regression upon TCD
      examination. In a univariate analysis, the history of ischemic stroke (P=0.023),
      the presence of significant carotid stenosis (P=0.027), the prescription of
      aspirin only (P=0.046), the grade of stenosis in the MRA (P=0.0048), and the
      platelet aggregability for ADP (P=0.015) were significantly associated with the
      progression of MCA stenosis. After multiple logistic regression analysis, the
      grades of stenosis and platelet aggregability for ADP were independent factors
      related to the progression of MCA stenosis. In this study, the grade of MCA
      stenosis on angiography might be an important factor to predict the progression
      upon serial TCD examination. Also, the extent of inhibition of platelet
      activation could be a possible role to determine on the progression of MCA
      stenosis.

PMID- 17541766
TI  - Metal Cu(II) and Zn(II) bipyridyls as inhibitors of lactate dehydrogenase.
AB  - Metal complex-protein interaction is an evolving concept for determining cellular
      targets of metallodrugs. Lacatate dehydrogenase (LDH) is critically implicated in
      tumor growth and therefore, considered to be an important target protein for anti
      tumor metal complexes. Due to efficient biocompatibility of copper (Cu(2+)) and
      zinc (Zn(2+)), we synthesized CubpyAc(2) . H(2)O (Cu-bpy) and ZnbpyAc(2) . H(2)O
      (Zn-bpy; where bpy = 2,2' bipyridine, Ac = CH(3)COO(-)) complexes and evaluated
      their interaction with and modulation of LDH in mouse tissues. The increasing
      concentration of both the complexes showed a significant shift in UV-Vis spectra
      of LDH. The binding constant data (Kc = 1 x 10(3) M(-1) for Cu-bpy and 7 x 10(6)
      M(-1) for Zn-bpy) suggested that Zn-bpy-LDH interaction is stronger than that of
      Cu-bpy-LDH. LDH modulating potential of the complexes were monitored by perfusing
      the mice tissues with non-toxic doses of Cu-bpy and Zn-bpy followed by activity
      measurement and analysis of LDH isozymes on non-denaturing polyacrylamide gel
      electrophoresis (PAGE). As compared to the control sets, Cu-bpy caused a
      significant decline (P < 0.05-0.001) in the activity of LDH in all the tissues
      studied. However, Zn-bpy showed inhibition of LDH only in liver (P < 0.01),
      kidney (P < 0.001) and heart (P < 0.01), but with no effect in spleen, brain and
      skeletal muscle tissues. PAGE analysis suggested that all the five LDH isozymes
      are equally sensitive to both the complexes in the respective tissues. The
      results suggest that Cu- and Zn-bpy are able to interact with and inhibit LDH, a
      tumor growth supportive target protein at tissue level.

PMID- 17541767
TI  - Bacterial contamination and antibiotic resistance in fecal coliforms from glacial
      water runoff.

PMID- 17541768
TI  - Genetic diversity of plankton community as depicted by PCR-DGGE fingerprinting
      and its relation to morphological composition and environmental factors in Lake
      Donghu.
AB  - To collect information about the genetic diversity of the plankton community and
      to study how plankton respond to environmental conditions, plankton samples were
      collected from five stations representing different trophic levels in a shallow,
      eutrophic lake (Lake Donghu), and investigated by PCR-DGGE fingerprinting. A
      total of 100 bands (61 of 16S rDNA bands and 39 of 18S rDNA bands) were detected.
      The DGGE bands unique to any single station accounted for 38% of the total bands,
      whereas common bands detected at all five stations accounted for only 11%. Using
      UPGMA clustering and MDS ordination of DGGE fingerprints, stations I and II were
      found to initially group together into one cluster, which was later joined by
      station V. Stations III and IV were isolated into two separate groups of one
      station each. Some differences in grouping relationships were found when analysis
      was completed on the basis of chemical characteristics and morphological
      composition, with zooplankton composition showing the greatest variability.
      However, the most similar stations (I and II) were always initially grouped into
      one cluster. Moreover, stations that exhibited the same or similar trophic level
      (stations III and IV), but different concentrations of heavy metals, were further
      differentiated by the DGGE method. Results of the present study indicated that
      PCR-DGGE fingerprinting was more sensitive than the traditional methods, as other
      studies suggested. Additionally, PCR-DGGE appears to be more appropriate for
      diversity characterization of the plankton community, as it is more canonical,
      systematic, and effective. Most importantly, fingerprinting results are more
      convenient for the comparative analyses between different studies. Therefore, the
      use of the described fingerprinting analysis may provide an operable and
      sensitive biomonitoring approach to identify critical, and potentially negative,
      stress within an aquatic ecosystem.

PMID- 17541770
TI  - What is new in ventilation strategies for the neonate?
AB  - A large number of ventilation strategies are now available for the neonate. This
      review has focused on new information, that is, studies published since 2000 and
      the implication of their results for current clinical practice. Meta-analysis of
      randomised trials has demonstrated that assist control and synchronous
      intermittent mandatory ventilation (SIMV) shortens the duration of ventilation
      only if started in the recovery rather than the early stage of respiratory
      disease. A recent randomised trial demonstrated pressure-regulated volume control
      ventilation may also have no advantages if started early. Weaning by SIMV with
      pressure support is better (reducing oxygen dependency) than SIMV alone. Meta
      analysis of volume-targeted ventilation demonstrated significant reductions in
      the duration of ventilation and pneumothorax, but the trials were small and of
      different designs. Volume guarantee may provide more consistent blood gas
      control. The level of volume targeting appears to be crucial to the success of
      this technique. Meta-analysis of randomised trials of prophylactic high-frequency
      oscillation trials has shown a modest reduction in bronchopulmonary dysplasia.
      Randomised trials have failed to confirm the advantages of nasal continuous
      positive airway pressure (NCPAP) seen in various non-randomised studies; however,
      the randomised trials reported to date have been small. Inhaled nitric oxide (NO)
      does not improve the outcome of prematurely born infants with severe respiratory
      failure, but early low-dose prolonged iNO appears to have benefits that merit
      further testing. More randomised trials with long-term outcomes are required to
      identify the optimal ventilation strategy(ies) for the neonate.

PMID- 17541769
TI  - Ion channel gene expression in the inner ear.
AB  - The ion channel genome is still being defined despite numerous publications on
      the subject. The ion channel transcriptome is even more difficult to assess.
      Using high-throughput computational tools, we surveyed all available inner ear
      cDNA libraries to identify genes coding for ion channels. We mapped over 100,000
      expressed sequence tags (ESTs) derived from human cochlea, mouse organ of Corti,
      mouse and zebrafish inner ear, and rat vestibular end organs to Homo sapiens, Mus
      musculus, Danio rerio, and Rattus norvegicus genomes. A survey of EST data alone
      reveals that at least a third of the ion channel genome is expressed in the inner
      ear, with highest expression occurring in hair cell-enriched mouse organ of Corti
      and rat vestibule. Our data and comparisons with other experimental techniques
      that measure gene expression show that every method has its limitations and does
      not per se provide a complete coverage of the inner ear ion channelome. In
      addition, the data show that most genes produce alternative transcripts with the
      same spectrum across multiple organisms, no ion channel gene variants are unique
      to the inner ear, and many splice variants have yet to be annotated. Our high
      throughput approach offers a qualitative computational and experimental analysis
      of ion channel genes in inner ear cDNA collections. A lack of data and incomplete
      gene annotations prevent both rigorous statistical analyses and comparisons of
      entire ion channelomes derived from different tissues and organisms.

PMID- 17541771
TI  - Reliability of lymphatic mapping after wide local excision of cutaneous melanoma.
AB  - BACKGROUND: Since the advent of sentinel lymph node (SLN) biopsy, patients with
      cutaneous melanoma have been referred to surgeons for consideration for SLN
      biopsy, sometimes even after the wide local excision (WLE) of the primary
      melanoma has been performed. This has raised the question of the reliability and
      validity of a lymphoscintigram performed for lymphatic mapping of the SLN after
      there has been anatomic rearrangement of the skin following the WLE of this
      primary melanoma. METHODS: We conducted a prospective study of 20 consecutive
      patients with cutaneous melanomas with thickness less than 1.00 mm, who
      volunteered to undergo preoperative and postoperative lymphatic mapping to
      determine if there were any changes in the lymph nodes that were identified
      following the WLE of the primary melanoma. Each of the patients had a resection
      with a minimum of 1.0 cm margin, and closure of their wounds with either
      transposition flap or double advancement flaps. RESULTS: Lymphatic mapping was
      clearly identified in all 20 patients. One patient declined to undergo
      postoperative lymphatic mapping. Postoperative lymphatic mapping performed in the
      remaining 19 patients 2-4 weeks following WLE was identical to the preoperative
      mapping in 13 patients (68%), showed additional lymph nodes in 4-5 patients (21
      26%), and showed fewer lymph nodes in 1-2 patients (5-10%). CONCLUSIONS:
      Lymphatic mapping performed after a WLE of a primary cutaneous melanoma should be
      as reliable in identifying the SLN as a preoperative lymphatic mapping in 90% of
      the patients.

PMID- 17541772
TI  - Critical analysis of treatment failure after complete cytoreductive surgery and
      perioperative intraperitoneal chemotherapy for peritoneal dissemination from
      appendiceal mucinous neoplasms.
AB  - BACKGROUND: Cytoreductive surgery (CRS) combined with perioperative
      intraperitoneal chemotherapy (PIC) has been suggested as a treatment strategy for
      peritoneal carcinomatosis. The objective of this data analysis was to study
      treatment failure after complete cytoreduction for peritoneal dissemination from
      appendiceal mucinous neoplasms. METHODS: Before June 2006, a total of 402
      patients with peritoneal dissemination from appendiceal mucinous neoplasms
      underwent complete cytoreduction and PIC at the Washington Cancer Institute.
      Patient characteristics, pathologic features, and treatment-related data were
      obtained from a prospective database. Survival analyses were performed by the
      Kaplan-Meier method and the Cox regression model. RESULTS: After a median follow
      up of 66 months, the 5- and 10-year progression-free survival rates for these 402
      patients were 70% and 67%, respectively. Disease progression was the only
      independent risk factor for a reduced overall survival. One hundred eleven
      patients (28%) developed progressive disease. Of these, 98 patients underwent
      second-time and 26 patients third-time CRS and PIC. Complete cytoreduction after
      repeat surgery was the only independent prognostic factor for improved survival.
      The most common sites of treatment failure were on the small bowel and in the
      pelvis. CONCLUSIONS: The present study reported the patterns of treatment failure
      after complete cytoreduction and demonstrated that a disease-free state is
      important for long-term survival in peritoneal dissemination from appendiceal
      mucinous neoplasms. Repeat complete cytoreduction should be pursued when possible
      and is associated with improved overall survival in patients with recurrent
      disease.

PMID- 17541775
TI  - Knockout of crtB or crtI gene blocks the carotenoid biosynthetic pathway in
      Deinococcus radiodurans R1 and influences its resistance to oxidative DNA
      damaging agents due to change of free radicals scavenging ability.
AB  - Deinococcus radiodurans R1, a red-pigmented strain of the extremely
      radioresistant genus Deinococcus, contains a major carotenoid namely
      deinoxanthin. The high resistance of this organism against the lethal actions of
      DNA-damaging agents including ionizing radiation and ultraviolet light (UV) has
      been widely reported. However, the possible antioxidant role of carotenoids in
      this strain has not been completely elucidated. In this study, we constructed two
      colorless mutants by knockout of crtB and crtI genes, respectively. Comparative
      analysis of the two colorless mutants and the wild type showed that the two
      colorless mutants were more sensitive to ionizing radiation, UV, and hydrogen
      peroxide, but not to mitomycin-C (MMC). With electron spin resonance (ESR) and
      spin trapping techniques, we observed that hydroxyl radical signals occurred in
      the suspensions of UV irradiated Deinococcus radiodurans cells and the intensity
      of signals was influenced by carotenoids levels. We further showed that the
      carotenoid extract from the wild type could obviously scavenge superoxide anions
      generated by the irradiated riboflavin/EDTA system. These results suggest that
      carotenoids in D. radiodurans R1 function as free radical scavengers to protect
      this organism against the deleterious effects of oxidative DNA-damaging agents.

PMID- 17541776
TI  - Phosphate sensing in Synechocystis sp. PCC 6803: SphU and the SphS-SphR two
      component regulatory system.
AB  - The Pho regulon is controlled by the histidine kinase-response regulator pair
      SphS-SphR in many cyanobacteria and up-regulation of the Pho regulon can be
      monitored by measuring alkaline phosphatase activity. However, the mechanism
      regulating signal transduction between SphS and SphR has not been described. We
      have created a cyanobacterial strain allowing the introduction of mutations into
      the transmitter domain of SphS. Mutations at Thr-167, adjacent to the H motif of
      SphS, introduce elevated alkaline phosphatase activity in the presence of
      phosphate and an enhancement of alkaline phosphatase activity, when compared to
      the control strain, in phosphate-limiting media. SphU acts as a negative
      regulator of the SphS-SphR system in Synechocystis sp. PCC 6803 and we show that
      constitutive alkaline phosphatase activity in the absence of SphU requires signal
      transduction through SphS and SphR. However, constitutive activity in the absence
      of SphU is severely attenuated in the DeltaSphU:SphS-T167N mutant. Our data
      suggest that Thr-167 contributes to the mechanism underlying regulation by SphU.
      We have also assembled a deletion mutant system allowing the introduction of
      mutations into SphR and show that Gly-225 and Trp-236, which are both conserved
      in SphR from cyanobacteria, are essential for activation of the Pho regulon under
      phosphate-limiting conditions.

PMID- 17541777
TI  - Identification and characterization of two Streptomyces davawensis riboflavin
      biosynthesis gene clusters.
AB  - In Streptomyces davawensis roseoflavin is synthesized from GTP and ribulose-5
      phosphate through riboflavin. As a first step towards the molecular analysis of
      flavin metabolism in S. davawensis the genes involved in riboflavin biosynthesis
      were cloned by hybridization of heterologous probes to a genomic library on a
      high-density colony-array. The genes ribB (riboflavin synthase, alpha-chain; EC
      2.5.1.9), ribM (putative membrane protein), ribA (bifunctional GTP cyclohydrolase
      II/3,4-dihydroxy-2-butanone-4-phosphate synthase; EC 3.5.4.25) and ribH (lumazine
      synthase; EC 2.5.1.9) are organized in an operon-like cluster. Northern blot
      analysis of this cluster revealed two transcripts of 1.7 and 3.1 kb,
      respectively. The gene ribB was overexpressed in Escherichia coli. The specific
      riboflavin synthase activity in a cell-free extract of a recombinant strain was
      0.246 nmol mg(-1 )min(-1). Overexpression of ribM enhanced the transport of
      riboflavin in the corresponding recombinant E. coli strain. Furthermore,
      overexpression of ribM increased roseoflavin sensitivity of E. coli. On another
      subgenomic fragment a putative S. davawensis ribG gene coding for the missing
      pyrimidine deaminase/reductase (EC 3.5.4.26 and EC 1.1.1.193) of the riboflavin
      biosynthetic pathway and ribY coding for a second (monofunctional) GTP
      cyclohydrolase II were identified.

PMID- 17541778
TI  - Role of nitrite reductase in the ammonia-oxidizing pathway of Nitrosomonas
      europaea.
AB  - Metabolism of ammonia (NH(3)) and hydroxylamine (NH(2)OH) by wild-type and a
      nitrite reductase (nirK) deficient mutant of Nitrosomonas europaea was
      investigated to clarify the role of NirK in the NH(3) oxidation pathway. NirK
      deficient N. europaea grew more slowly, consumed less NH(3), had a lower rate of
      nitrite (NO(2) (-)) production, and a significantly higher rate of nitrous oxide
      (N(2)O) production than the wild-type when incubated with NH(3) under high O(2)
      tension. In incubations with NH(3) under low O(2) tension, NirK-deficient N.
      europaea grew more slowly, but had only modest differences in NH(3) oxidation and
      product formation rates relative to the wild-type. In contrast, the nirK mutant
      oxidized NH(2)OH to NO(2) (-) at consistently slower rates than the wild-type,
      especially under low O(2) tension, and lost a significant pool of NH(2)OH-N to
      products other than NO(2) (-) and N(2)O. The rate of N(2)O production by the nirK
      mutant was ca. three times higher than the wild-type during hydrazine-dependent
      NO(2) (-) reduction under both high and low O(2) tension. Together, the results
      indicate that NirK activity supports growth of N. europaea by supporting the
      oxidation of NH(3) to NO(2) (-) via NH(2)OH, and stimulation of hydrazine
      dependent NO(2) (-) reduction by NirK-deficient N. europaea indicated the
      presence of an alternative, enzymatic pathway for N(2)O production.

PMID- 17541779
TI  - Reciprocal effects of response contingent and noncontingent intravenous heroin on
      in vivo nucleus accumbens shell versus core dopamine in the rat: a repeated
      sampling microdialysis study.
AB  - RATIONALE: Although passive administration of heroin to drug-naive rats increases
      extracellular dopamine (DA) in the nucleus accumbens (NAc), its ability to do so
      also after active drug exposure (self-administration) is debated. OBJECTIVES:
      This study investigated by repeated microdialysis sampling the inter- and
      intrasession changes in the responsiveness of the NAc shell and core DA and the
      behavioral effects of active and passive heroin exposure in the intravenous self
      administration/yoked paradigm. MATERIALS AND METHODS: Rats were implanted with
      jugular catheters and bilateral intracerebral chronic guide cannulae. Nose poking
      in the active hole by master rats resulted in heroin administration to the same
      subjects and to their yoked mates. Concentric microdialysis probes were inserted
      daily in the guide cannulae, and changes in dialysate DA in response to heroin
      exposure (0.05 mg/kg) were monitored in the same subject for 90 min for 4 weeks.
      Behavior associated with heroin exposure, distinguished into nonstereotyped and
      stereotyped, was also recorded. RESULTS: Dialysate DA increased preferentially in
      the shell of master rats from the first session (+112%) and throughout the 4
      weeks of self-administration (+130-140%). In yoked rats, a preferential but
      lesser increase in DA in the shell was observed only on the first session (+60%),
      as the DA response in the NAc core increased progressively (+25-118%), so that
      within a week, the shell/core ratio was reversed, and this pattern was maintained
      for the following 2 weeks. Yoked rats showed a progressive and larger increase in
      stereotyped behaviors than master rats. CONCLUSIONS: Chronic heroin self
      administration increases extracellular DA preferentially in the NAc shell.
      Response-noncontingent heroin administration is particularly prone, compared to
      response-contingent administration, to induce behavioral and biochemical
      sensitization.

PMID- 17541780
TI  - MR imaging findings of eosinophilic cystitis in an 8-year-old girl.
AB  - Eosinophilic cystitis is a rare inflammatory condition of the urinary bladder of
      unknown aetiology and characterized by eosinophilic infiltration of the bladder
      wall. We report the unique MR findings of eosinophilic cystitis in an 8-year-old
      girl who presented with peripheral eosinophilia. MR imaging revealed smooth and
      nearly circumferential thickening of the bladder wall showing distinct low signal
      intensity on T2-weighted images, which may histologically represent high
      cellularity due to massive eosinophilic infiltration.

PMID- 17541781
TI  - Sleeve fracture at the superior pole of the patella.
AB  - We present a sleeve fracture at the superior pole of the patella in a 12-year-old
      boy. Sleeve fractures at the inferior pole of the patella have been well
      described in the orthopedic and radiologic literature. However, a similar injury
      at the superior pole of the patella is relatively rare. We hope that awareness of
      this unusual injury and its imaging findings will allow timely diagnosis and
      intervention.

PMID- 17541782
TI  - Enhanced production of epsilon-caprolactone by overexpression of NADPH
      regenerating glucose 6-phosphate dehydrogenase in recombinant Escherichia coli
      harboring cyclohexanone monooxygenase gene.
AB  - Whole-cell conversion of cyclohexanone to epsilon-caprolactone was attempted by
      recombinant Escherichia coli BL21(DE3) expressing cyclohexanone monooxygenase
      (CHMO) of Acinetobacter calcoaceticus NCIMB 9871. High concentrations of
      cyclohexanone and epsilon-caprolactone reduced CHMO-mediated bioconversion of
      cyclohexanone to epsilon-caprolactone in the resting recombinant E. coli cells.
      Metabolically active cells were employed by adopting a fed-batch culture to
      improve the production of epsilon-caprolactone from cyclohexanone. A glucose
      limited fed-batch Baeyer-Villiger oxidation where a cyclohexanone level was
      maintained less than 6 g/l resulted in a maximum epsilon-caprolactone
      concentration of 11.0 g/l. The maximum epsilon-caprolactone concentration was
      improved further to 15.3 g/l by coexpression of glucose-6-phosphate
      dehydrogenase, an NADPH-generating enzyme encoded by the zwf gene which
      corresponded to a 39% enhancement in epsilon-caprolactone concentration compared
      with the control experiment performed under the same conditions.

PMID- 17541783
TI  - Tuning posture to body load: decreases in load produce discrete sensory signals
      in the legs of freely standing cockroaches.
AB  - Decreases in load are important cues in the control of posture and walking. We
      recorded activities of the tibial campaniform sensilla, receptors that monitor
      forces as strains in the exoskeleton, in the middle legs of freely moving
      cockroaches. Small magnets were attached to the thorax and body load was changed
      by applying currents to a coil below the substrate. Body position was monitored
      by video recording. The tibial sensilla are organized into proximal and distal
      subgroups that have different response properties and reflex effects: proximal
      sensilla excite extensor motoneurons while distal receptors inhibit extensor
      firing. Sudden load decreases elicited bursts from distal sensilla, while
      increased load excited proximal receptors. The onset of sensory discharges
      closely approximated the time of peak velocity of body movement in both load
      decreases and increases. Firing of distal sensilla rapidly adapted to sustained
      unloading, while proximal sensilla discharged tonically to load increases. Load
      decreases of small amplitude or at low rates produced only inhibition of proximal
      activity while decrements of larger size or rate elicited distal firing. These
      response properties may provide discrete signals that either modulate excitatory
      extensor drive during small load variations or inhibit support prior to
      compensatory stepping or initiation of swing.

PMID- 17541784
TI  - Parallel manifestation of Crohn's disease and acute pericarditis: a report of two
      cases.
AB  - Pericarditis is an uncommon extraintestinal manifestation of inflammatory bowel
      disease (IBD), which may occur at any time during its natural course. Moreover,
      it may be associated with the medications used to treat IBD, especially
      mesalamine. We report on two patients with acute pericarditis who were
      subsequently diagnosed with Crohn's disease. It is likely that mild,
      longstanding, virtually asymptomatic intestinal disease preceded the onset of
      pericarditis in both cases.

PMID- 17541785
TI  - Frontotemporal lobar degeneration: recent progress in antemortem diagnosis.
AB  - Frontotemporal lobar degeneration (FTLD) is a neurodegenerative disorder
      characterized by changes in behaviour and language dysfunction. Two broad
      pathological subdivisions of FTLD are recognized in a recent classification
      scheme based on biochemical features: tau-positive pathology due to the
      accumulation of various forms of the microtubule-associated protein tau, such as
      FTLD with Pick bodies and corticobasal degeneration; and tau-negative pathology
      such as frontotemporal lobar degeneration with ubiquitin/TDP-43-immunoreactive
      inclusions. Etiologically based treatments aim to target the mechanisms
      underlying the accumulation of these abnormal proteins in these conditions. It is
      essential for us to develop biomarkers that support the accurate diagnosis of the
      specific diseases causing FTLD. These biomarkers also can be useful in assessing
      efficacy during treatment trials. This review summarizes the epidemiologic,
      clinical, neuropsychological, imaging and cerebrospinal fluid (CSF) biomarker
      features that can help identify these pathologically defined conditions during
      life.

PMID- 17541786
TI  - New method for height estimation of subjects represented in photograms taken from
      video surveillance systems.
AB  - The article describes a method developed and applied by the authors for the
      purpose of determining the height of subjects taped on video surveillance
      systems. The determination of height is obtained by developing a virtual
      telecamera having the same characteristics of the video surveillance system with
      which the images have been shot. The results demonstrate that height is a
      parameter that can be accurately estimated with the method proposed, in the
      experimental conditions described, and consequently, can be utilized in probatory
      inquiry.

PMID- 17541787
TI  - Hematological response and diving response during apnea and apnea with face
      immersion.
AB  - Increased hematocrit (Hct) attributable to splenic contraction accompanies human
      apneic diving or apnea with face immersion. Apnea also causes heart rate
      reduction and peripheral vasoconstriction, i.e., a cardiovascular diving
      response, which is augmented by face immersion. The aim was to study the role of
      apnea and facial immersion in the initiation of the hematological response and to
      relate this to the cardiovascular diving response and its oxygen conservation
      during repeated apneas. Seven male volunteers performed two series of five apneas
      of fixed near-maximal duration: one series in air (A) and the other with facial
      immersion in 10 degrees C water (FIA). Apneas were spaced by 2 min and series by
      20 min of rest. Venous blood samples, taken before and after each apnea, were
      analysed for Hct, hemoglobin concentration (Hb), lactic acid, blood gases and pH.
      Heart rate, skin capillary blood flow and arterial oxygen saturation were
      continuously measured non-invasively. A transient increase of Hct and Hb by
      approximately 4% developed progressively across both series. As no increase of
      the response resulted with face immersion, we concluded that the apnea, or its
      consequences, is the major stimulus evoking splenic contraction. An augmented
      cardiovascular diving response occurred during FIA compared to A. Arterial oxygen
      saturation remained higher, venous oxygen stores were more depleted and lactic
      acid accumulation was higher across the FIA series, indicating oxygen
      conservation with the more powerful diving response. This study shows that the
      hematological response is not involved in causing the difference in oxygen
      saturation between apnea and apnea with face immersion.

PMID- 17541788
TI  - The selectivity, voltage-dependence and acid sensitivity of the tandem pore
      potassium channel TASK-1: contributions of the pore domains.
AB  - We have investigated the contribution to ionic selectivity of residues in the
      selectivity filter and pore helices of the P1 and P2 domains in the acid
      sensitive potassium channel TASK-1. We used site directed mutagenesis and
      electrophysiological studies, assisted by structural models built through
      computational methods. We have measured selectivity in channels expressed in
      Xenopus oocytes, using voltage clamp to measure shifts in reversal potential and
      current amplitudes when Rb+ or Na+ replaced extracellular K+. Both P1 and P2
      contribute to selectivity, and most mutations, including mutation of residues in
      the triplets GYG and GFG in P1 and P2, made channels non-selective. We interpret
      the effects of these--and of other mutations--in terms of the way the pore is
      likely to be stabilised structurally. We show also that residues in the outer
      pore mouth contribute to selectivity in TASK-1. Mutations resulting in loss of
      selectivity (e.g. I94S, G95A) were associated with slowing of the response of
      channels to depolarisation. More important physiologically, pH sensitivity is
      also lost or altered by such mutations. Mutations that retained selectivity (e.g.
      I94L, I94V) also retained their response to acidification. It is likely that
      responses both to voltage and pH changes involve gating at the selectivity
      filter.

PMID- 17541789
TI  - Overexpression of glycerol-3-phosphate acyltransferase gene improves chilling
      tolerance in tomato.
AB  - A tomato (Lycopersicon esculentum Mill.) glycerol-3-phosphate acyltransferase
      gene (LeGPAT) was isolated. The deduced amino acid sequence revealed that LeGPAT
      contained four acyltransferase domains, showing high identities with GPAT in
      other plant species. A GFP fusion protein of LeGPAT was targeted to chloroplast
      in cowpea mesophyll protoplast. RNA gel blot showed that the mRNA accumulation of
      LeGPAT in the wild type (WT) was induced by chilling temperature. Higher
      expression levels were observed when tomato leaves were exposed to 4 degrees C
      for 4 h. RNA gel and western blot analysis confirmed that the sense gene LeGPAT
      was transferred into the tomato genome and overexpressed under the control of 35S
      CaMV. Although tomato is classified as a chilling-sensitive plant, LeGPAT
      exhibited selectivity to 18:1 over 16:0. Overexpression of LeGPAT increased total
      activity of LeGPAT and cis-unsaturated fatty acids in PG in thylakoid membrane.
      Chilling treatment induced less ion leakage from the transgenic plants than from
      the WT. The photosynthetic rate and the maximal photochemical efficiency of PS II
      (Fv/Fm) in transgenic plants decreased more slowly during chilling stress and
      recovered faster than in WT under optimal conditions. The oxidizable P700 in both
      WT and transgenic plants decreased obviously at chilling temperature under low
      irradiance, but the oxidizable P700 recovered faster in transgenic plants than in
      the WT. These results indicate that overexpression of LeGPAT increased the levels
      of PG cis-unsaturated fatty acids in thylakoid membrane, which was beneficial for
      the recovery of chilling-induced PS I photoinhibition in tomato.

PMID- 17541790
TI  - Hang on or run? Copepod mating versus predation risk in contrasting environments.
AB  - Mating durations of copepods were found to differ significantly between fishless
      high-altitude waters and lowland lakes containing fish. In lowland species the
      whole mating process was completed within a few minutes, but it averaged over an
      hour in high-altitude species. Alpine copepods showed a prolonged post-copulatory
      association between mates, during which the male clasped the female for an
      extended period after spermatophore transfer, while in lowland species males
      abandoned their partner immediately after copulation. Prolonged associations also
      occurred after transfer of spermatophores to heterospecific females with shorter
      conspecific mating duration, suggesting that male interests largely dictate the
      time spent in tandem. The differences observed may be adaptations to environments
      with different predation pressure, as pairs in tandem are more conspicuous and
      less reactive than single animals. We argue that differences in mating behavior
      and mating duration evolved under sexual versus natural selection, reflecting
      trade-offs between enhancement of fertilization success and reduction of
      vulnerability to visual predation. In fishless mountain lakes with high
      intrasexual competition, guarding males can reduce the risk of spermatophore
      displacement or the risk that the female will accept sperm from rival males
      without increased risk of being eaten, thereby maximizing paternity. Populations
      from fishless alpine lakes further differed from lowland species by exhibiting
      higher female/male size dimorphism and more intense pigmentation. While these
      traits vary between populations according to predation pressure, mating duration
      appears to be more species-specific.

PMID- 17541791
TI  - Hyperinsulinemia in pediatric patients with chronic kidney disease: the role of
      tumor necrosis factor-alpha.
AB  - We sought to determine the prevalence of hyperinsulinemia and insulin resistance
      in pediatric patients with chronic kidney disease (CKD) stages 2-4. Data were
      collected on 43 subjects, aged 6-21 years with mean glomerular filtration rate
      (GFR) = 47 ml/min per 1.73 m(2) body surface area. Patients were grouped by body
      mass index (BMI) as either non-lean (>85th percentile) or lean (<or=85th
      percentile). Fourteen (33%) subjects had hyperinsulinemia, and seven (16%) had
      elevated homeostasis model assessment of insulin resistance (HOMA-IR). Non-lean
      subjects had a higher serum insulin level (21.0 microU/ml vs 13.4 microU/ml, P <
      0.0001) and HOMA-IR (4.9 vs 3.2, P < 0.001) than lean subjects had. The
      prevalence of hyperinsulinemia was higher in non-lean patients (40%) than in lean
      patients (29%) but was not statistically significant. High HOMA-IR was present in
      six (40%) non-lean subjects and in one lean subject (P < 0.001). Correlation
      analysis demonstrated that serum insulin level was significantly associated with
      BMI, leptin and tumor necrosis factor (TNF)-alpha. Stepwise regression determined
      that increased BMI (P = 0.003) and TNF-alpha (P = 0.01) independently predicted
      higher insulin level in the whole cohort. Separate analysis for lean subjects
      showed no significant associations between serum insulin level and BMI; TNF-alpha
      was the only independent predictor of serum insulin (beta = 1.11, P = 0.01). We
      conclude that hyperinsulinemia and insulin resistance are frequent in pediatric
      CKD. In lean patients inflammation appears to be an important determinant of
      serum insulin level.

PMID- 17541792
TI  - Urinary tract infection caused by Haemophilus influenzae and Haemophilus
      parainfluenzae in children.
AB  - There are few reports on urinary tract infections caused by Haemophilus
      influenzae or Haemophilus parainfluenzae in children. The true incidence is not
      known, since bacteria of Haemophilus species do not grow in standard urine
      culture media. With the objective of investigating the occurrence and character
      of urinary tract infections (UTIs) caused by Haemophilus bacteria in children, we
      searched the files of our UTI clinic. Over a 24-year period 36 children with
      Haemophilus spp. bacteriuria were identified out of a total of more than 5,000
      UTI episodes. There was a significant gender difference in that Haemophilus
      influenzae dominated in girls and Haemophilus parainfluenzae in boys. With one
      exception, all children had important urinary tract abnormalities, such as
      malformation, gross reflux or bladder dysfunction. Permanent renal damage was
      seen in 25. We conclude that growth of Haemophilus bacteria in urine is
      associated with serious urinary tract abnormalities. The inability of bacteria of
      the Haemophilus species to grow in standard media commonly used for culture of
      uropathogens suggests that the true frequency of these strains as a cause of
      urinary tract infections is underestimated.

PMID- 17541793
TI  - Strontium oral load test in children with idiopathic hypercalciuria.
AB  - Increased intestinal calcium absorption may play an important role in the
      pathogenesis of idiopathic hypercalciuria in children. Calcium absorption was
      assessed by an oral strontium load test in 22 prepubertal children (13 male) with
      idiopathic hypercalciuria, urinary calcium excretion 6.48 +/- 0.60 mg/kg per day
      (range 4.12-13.40 mg/kg per day), and ten healthy, young, normocalciuric controls
      (six male). After administration of 2.65 mg/kg of strontium chloride (SrCl(2)),
      the serum concentrations of strontium at 30 min, 60 min, 120 min, 240 min, and
      the fraction of the absorbed dose (FAD%) at 30 min, 60 min and 240 min, were
      similar in both groups. FAD% at 120 min was lower (P < 0.05) in hypercalciuric
      children than in controls (11.84 +/- 0.96% vs 15.87 +/- 1.77%). Values of the
      area under the curve were not different between both groups. In children with
      idiopathic hypercalciuria, serum basal intact parathyroid hormone (PTH) (r = 
      0.59, P = 0.004) and the 1,25-dihydroxyvitamin D/PTH ratio (r = 0.65; P = 0.001)
      were correlated with the serum concentration of strontium at 60 min. The study
      reported here provides, for the first time, the results of a strontium oral load
      test in children with idiopathic hypercalciuria. With this method no major
      alterations of intestinal calcium absorption were found in this disorder.

PMID- 17541794
TI  - Ab initio and DFT study of the aromaticity of some Fulvalenes derived from
      Methylidenecyclopropabenzene.
AB  - Methylidencyclopropabenzene (MCPB) 1 and Fulvalenes 2-4 are molecules of special
      interest due to the relation between structure and aromaticity. The aim of this
      work was to analyze this relation and to quantify the aromaticity in 1-4 using
      different methods. Magnetic properties are directly related with aromaticity;
      here we studied the magnetic susceptibility and the anisotropy of the magnetic
      susceptibility. Nucleus indepedent chemical shift (NICS) and the anisotropy of
      the induced current density (ACID) were also employed. Tools of very different
      nature, geometric indexes HOMA and Bird, were determinated too for 1-4. All of
      these measures were found to be in agreement.

PMID- 17541795
TI  - Frequency spectrum and amplitude analysis of dark- and light-adapted oscillatory
      potentials in albino mouse, rat and rabbit.
AB  - We studied frequency spectrum, implicit time and amplitude of oscillatory
      potentials (OPs) in albino mice, rats, and rabbits. Oscillatory potentials were
      extracted digitally from dark- and light-adapted electroretinograms (ERGs)
      recorded with a protocol commonly used in our laboratory. The frequency spectra
      of OPs were analyzed by using Fast Fourier Transform (FFT). Oscillatory potential
      amplitudes were calculated via numerically integrating the power spectrum.
      Oscillatory potential frequency spectra vary among species and are light
      intensity dependent. In dark-adapted ERG, mouse and rat OPs have one major
      component with a frequency peak at approximately 100 Hz. Rabbits show multiple
      frequency peaks with a low frequency peak around 75 Hz. In all the three species,
      the implicit time of light-adapted OP is longer than that of the dark-adapted
      OPs. At a given intensity, mice have the highest OP responses. Our data suggest
      that the commonly used bandpass of 75 Hz (or even 100 Hz) to 300 Hz for OP
      extraction is insufficient in these animals. In order to acquire the complete OP
      responses from the ERG signals, it is necessary to determine the OP frequency
      spectrum. In this study, the lower end cutoff frequency was set at 40 Hz in mice,
      65 Hz in rats and rabbits.

PMID- 17541796
TI  - Selective COX-2 inhibitors, eicosanoid synthesis and clinical outcomes: a case
      study of system failure.
AB  - Elucidation of differences between the active sites of COX-1 and COX-2 allowed
      the targeted design of the selective COX-2 inhibitors known as coxibs. They were
      marketed as non-steroidal anti-inflammatory drugs (NSAIDs) that had improved
      upper gastrointestinal (GI) safety compared with older non-selective NSAIDs such
      as diclofenac and naproxen. Two GI safety studies conducted with arthritis
      patients demonstrated that in terms of upper GI safety, celecoxib was not
      superior to diclofenac (CLASS study) but rofecoxib was superior to naproxen
      (VIGOR study). However, the VIGOR study revealed also that rofecoxib had
      increased cardiovascular (CV) risk compared with naproxen. This clinical outcome
      was supported by the existence of plausible eicosanoid-based biological
      mechanisms whereby selective COX-2 inhibition could increase CV risk.
      Nevertheless, the existence of CV risk with rofecoxib was successfully discounted
      by its pharmaceutical company owner, Merck & Co, with the assistance of
      specialist opinion leaders and rofecoxib achieved widespread clinical use for 4-5
      years. Rofecoxib was withdrawn from the market when several clinical trials in
      colorectal cancer and post-operative pain revealed increased CV risk with not
      only rofecoxib, but also coxibs. The commercial success of rofecoxib provides a
      case-study of failure of the medical journal literature to guide drug usage.
      Attention to ethical issues may have provided a more useful guide for
      prescribers.

PMID- 17541797
TI  - Polar and neutral lipid composition in the pelagic tunicate Pyrosoma atlanticum.
AB  - Structure and functioning of colonial pyrosomes are largely undescribed and their
      lipid characteristics have received limited attention. The aim of this paper is
      to fill this gap on one of the dominant species Pyrosoma atlanticum. Lipid
      content is tightly coupled to size and weight. Lipid composition shows a large
      dominance of structural polar lipids. Neutral lipids were dominated by sterols
      with low levels of acylglycerols and free fatty acids. Phospholipids show a
      dominance of PC with intermediate percentages of PE and DPG. Other constituents
      (PS, PI, LPC, sphingolipids) were present at lower levels. Fatty acid composition
      of DAG and TAG showed a dominance of saturated acids (16:0, 14:0), DHA and
      intermediate levels of MUFA. Phospholipids were dominated by DHA with values
      exceeding 30% of total FA in all categories except for PI, where lower
      percentages occurred. Saturated acids were second in abundance with MUFA showing
      intermediate concentrations. Sterols were dominated by 24-methylcholesta-5,22E
      dien-3beta-ol with more than 22% of the total sterol. Cholesterol (cholest-5-en
      3beta-ol) represented only 12 % of the total while 24-methylcholesta-5,24(28)E
      dien-3beta-ol accounted for 11% of the total sterols. The low levels of
      triacylglycerols and free fatty acids, coupled with high concentrations of
      glycolipids and phytoplankton-derived degraded chloropigments, is evidence of a
      direct link with the digestive activity and substantiate the idea of a high
      physiological turnover as an alternative to large lipid accumulation. The fatty
      acid and sterol profiles are consistent with a diverse phytoplankton diet, and a
      strong contribution of phospholipid classes to energy needs, including
      locomotion.

PMID- 17541798
TI  - Uniform fatty acid mobilization from anatomically distinct fat depots in the
      sable (Martes zibellina).
AB  - The mobilization of fatty acids (FA) is a selective process in humans, rodents
      and the few previously studied carnivores. The FA composition of and mobilization
      from different fat depots reflect the functions of adipose tissues, e.g. in
      energy storage or insulation. Sixteen farm-raised sables (Martes zibellina), a
      terrestrial mustelid, were assigned into a fed control group or fasted for 4
      days. The FA composition of the sable was relatively similar to other previously
      studied mustelids. The masses of the different fat depots decreased by 28-55%
      during fasting. The subcutaneous (sc) and intraabdominal (iab) fats had a uniform
      FA composition and the sable could mobilize both sc and iab FA. 18:3n-3, 18:4n-3
      and 16:1n-7 were effectively mobilized, while long-chain saturated (SFA) and
      monounsaturated FA (MUFA) increased in proportion. Relative mobilization (RM)
      correlated inversely with the FA chain length and Delta9-desaturation increased
      RM of several MUFA compared to SFA. The results reinforce the hypothesis that the
      terrestrial sable can utilize sc and iab fat depots as energy reserves during
      nutritional scarcity. The natural history of the species is an important
      determinant of the FA composition and RM between anatomically different fat
      depots.

PMID- 17541799
TI  - Efficacy of preoperative combined 18-fluorodeoxyglucose positron emission
      tomography and computed tomography for assessing primary rectal cancer response
      to neoadjuvant therapy.
AB  - PURPOSE: Efficacy of F-18 fluorodeoxyglucose positron emission tomography
      combined with computed tomography (FDG-PET/CT) for determining neoadjuvant
      therapy response in rectal cancer is not well established. We sought to evaluate
      serial FDG-PET/CT for assessing tumor down-staging, percentage residual tumor,
      and complete response or microscopic disease with rectal cancer neoadjuvant
      therapy. METHODS: Patients with rectal cancer undergoing neoadjuvant therapy,
      definitive surgical resection, and FDG-PET/CT before and 4-6 weeks after
      neoadjuvant treatment were included. Tumors were evaluated pretreatment and on
      final pathology for size and stage. FDG-PET/CT parameters assessed were visual
      response score (VRS), standardized uptake value (SUV), PET-derived tumor volume
      (PETvol), CT-derived tumor volume (CTvol), and total lesion glycolysis (delta
      TLG). RESULTS: Twenty-one rectal cancer patients over 3 years underwent
      neoadjuvant treatment, serial FDG-PET/CT, and resection. Complete response or
      microscopic disease (n = 7, 33%) was associated with higher Delta CTvol (AUC =
      0.82, p = 0.004) and Delta SUV (AUC = 0.79, p = 0.01). Tumor down-staging (n =
      14, 67%) was associated with greater Delta PETvol (AUC = 0.82, p < 0.001) and
      Delta SUV (AUC = 0.82, p < 0.001). Pathologic lymph node disease (n = 7, 33%)
      correlated with Delta CTvol (AUC = 0.75, p = 0.03) and Delta PETvol (AUC = 0.70,
      p = 0.08). CONCLUSION: FDG-PET/CT parameters were best for assessing tumor down
      staging and percentage of residual tumor after neoadjuvant treatment of rectal
      cancer and can potentially assist in treatment planning.

PMID- 17541800
TI  - Psychometric properties of the Korean version of the effort-reward imbalance
      questionnaire: a study in a petrochemical company.
AB  - OBJECTIVE: To evaluate the criterion validity, factorial validity, and internal
      consistency of Korean version of effort-reward imbalance (ERI) for the scales of
      effort, reward, and overcommitment as well as to examine the effect of
      psychosocial factors on physical and mental illness among petroleum refinery
      workers in South Korea. METHODS: The Korean version of ERI questionnaire was
      constructed using the translation and back-translation technique, and its
      psychometric properties were explored among 908 male workers in a large petroleum
      refinery in South Korea in 2002. Cronbach's alpha coefficient was used to test
      internal consistency. An exploratory factor analysis was conducted on all items
      of the instrument. Confirmatory factor analyses were conducted on each dimension
      of effort, reward and overcommitment. Physical and mental health was measured by
      self-rated health (SF-8). The lowest tertiles of the scores were defined as
      illness. Multiple logistic regression models were used to test the effect of job
      stress on the physical and mental health (criterion validity of ERI scales).
      RESULTS: The Cronbach's alpha coefficients for effort, reward, and overcommitment
      were 0.71, 0.86, and 0.75, respectively, indicating satisfactory internal
      consistency. Exploratory factor analysis found three latent factors, which
      closely corresponded to the theoretical structure of the ERI model. Acceptable
      construct validity was shown using confirmatory factor analysis. The highest
      tertile of effort-reward ratio was significantly associated with physical illness
      (OR 2.4, 95% CI 1.7-3.6) and mental illness (OR 2.9, 95% CI 2.0-4.2), compared to
      lower tertiles. Overcommitment was significantly associated with mental illness,
      but not with physical illness. CONCLUSIONS: These findings contribute to the
      validity and reliability of the Korean ERI questionnaire. Importantly, in the
      context of a rapid change in the labour market, the lack of reciprocity between
      efforts and rewards at work is strongly associated with self-rated physical and
      mental health.

PMID- 17541801
TI  - Crystal structure of the ferritin from the hyperthermophilic archaeal anaerobe
      Pyrococcus furiosus.
AB  - The crystal structure of the ferritin from the archaeon, hyperthermophile and
      anaerobe Pyrococcus furiosus (PfFtn) is presented. While many ferritin structures
      from bacteria to mammals have been reported, until now only one was available
      from archaea, the ferritin from Archaeoglobus fulgidus (AfFtn). The PfFtn 24-mer
      exhibits the 432 point-group symmetry that is characteristic of most ferritins,
      which suggests that the 23 symmetry found in the previously reported AfFtn is not
      a common feature of archaeal ferritins. Consequently, the four large pores that
      were found in AfFtn are not present in PfFtn. The structure has been solved by
      molecular replacement and refined at 2.75-Angstrom resolution to R = 0.195 and
      R(free) = 0.247. The ferroxidase center of the aerobically crystallized ferritin
      contains one iron at site A and shows sites B and C only upon iron or zinc
      soaking. Electron paramagnetic resonance studies suggest this iron depletion of
      the native ferroxidase center to be a result of a complexation of iron by the
      crystallization salt. The extreme thermostability of PfFtn is compared with that
      of eight structurally similar ferritins and is proposed to originate mostly from
      the observed high number of intrasubunit hydrogen bonds. A preservation of the
      monomer fold, rather than the 24-mer assembly, appears to be the most important
      factor that protects the ferritin from inactivation by heat.

PMID- 17541811
TI  - Historical height loss, vertebral deformity, and health-related quality of life
      in Hiroshima cohort study.
AB  - Height loss and vertebral deformity had independent effects on health-related
      quality of life evaluated by the European quality-of-life five-domain
      questionnaire (EQ-5D) in a cohort of 2,021 elderly Japanese men and women. Height
      loss aggravated EQ-5D more strongly than vertebral deformity in all domains, with
      different patterns. INTRODUCTION: Vertebral deformity reduces the activities of
      daily living and quality of life, and elevates mortality. Height loss is taken to
      be a sign of vertebral deformity, although other factors could also cause height
      loss. In this study, we examined the difference in EQ-5D between elderly with
      height loss and with vertebral deformity. METHODS: The subjects were 2,021 men
      and women aged 57-101 years from the Hiroshima Cohort who underwent health
      examinations in 2002-03 and responded to the EQ-5D. Vertebral deformity was
      assessed semi-quantitative methods using lateral chest and spine radiographs.
      Height was measured during the routine biennial examinations, which have been
      conducted since 1958. We used linear regression analyses, ordered polytomous
      logistic regression analyses, and Bonferroni tests. RESULTS: Eighty three men and
      314 women had prevalent vertebral deformity. The mean height loss was 2.2 cm for
      men and 3.9 cm for women. Height loss > or =4 cm (P < 0.01) and vertebral
      deformity (P = 0.04) were independent risk factors for low EQ-5D scores, after
      adjustment for sex and age. CONCLUSIONS: The present study showed that height
      loss and vertebral deformity affected EQ-5D significantly and independently in
      the elderly.

PMID- 17541812
TI  - Clinical and epidemiological features of rheumatic diseases in patients attending
      the university hospital in Kinshasa.
AB  - The aim of the present retrospective and hospital-based study was to describe
      epidemiological and clinical features of rheumatic diseases in patients attending
      the University Hospital of Kinshasa (UHK). Rheumatic complaint was a reason for
      consultation in 12.1% of outpatients attending the Department of Internal
      Medicine of the UHK. Osteoarthritis was the most common rheumatic disease
      (59.2%), followed by soft tissue rheumatism (16.1%), gout (9.3%), and
      spondylarthropathies (7.5%). The cumulative frequency of autoimmune diseases
      (rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis,
      dermatomyositis, and mixed connective tissues disease) and the frequency of
      osteoporosis were 5.2 and 2.7%, respectively. Lumbar spine was the part of the
      skeleton mostly affected by osteoarthritis. Pathological fractures in
      osteoporosis, subcutaneous nodules, rheumatoid factor, and erosive bone lesions
      in rheumatoid arthritis were rarely found. Compared to the previous studies
      performed in the same hospital, our results disclose a threefold increase of
      rheumatic outpatients. The paucity of erosive arthritis and extra-articular
      manifestations suggest the less severity of rheumatoid arthritis in our patients.
      Likewise, the absence of femoral and wrist osteoporotic fractures and the
      scarcity of advanced vertebral crush fractures suggest the mildness of
      osteoporosis.

PMID- 17541813
TI  - Modeling thermotherapy in vocal cords novel laser endoscopic treatment.
AB  - Vocal cords pathologies can be classified in difficulty of movement, lesion
      formation, and difficulty or lack of mucosal wave movement. There are therapies
      for the first two cases, but the last one presents nowadays no efficient
      solution. In this paper, a novel laser endoscopic thermotherapy treatment is
      proposed to improve vocal cords vibration in sulcus vocalis or slight scars by
      increasing temperature around 8 degrees C. To predict the availability of this
      treatment, a complete model of laser-tissue interaction is shown. Optical
      propagation radiation transport theory model is solved with a Monte Carlo
      approach, spatial-temporal thermal distributions are obtained via a bioheat
      equation, and thermal damage uses an Arrhenius integral. Two widely used lasers,
      Nd:YAG (1,064 nm) and KTP (532 nm), with different source powers, exposition
      times, and distances to vocal cords are considered to investigate the
      availability of an efficient and safe laser treatment.

PMID- 17541814
TI  - Hepatocellular carcinoma-associated gene 2 interacts with MAD2L2.
AB  - HCCA2 (hepatocellular carcinoma-associated gene 2) was initially identified as a
      HCC (hepatocellular carcinoma)-specific protein and subsequently, a long splice
      variant of HCCA2 was identified as a co-activator of transcription factor YY1
      (Yin Yang 1). To investigate the role of HCCA2 in HCC genesis and progression, we
      screened a human fetal liver cDNA library and identified a novel HCCA2
      interacting protein, MAD2L2 (MAD2 mitotic arrest deficient-like 2 (yeast)). The
      interaction between HCCA2 and MAD2L2 was confirmed by in vitro and in vivo
      binding assays and the interaction domain was mapped to the N-terminus of HCCA2
      by sequential deletion. HCCA2 and MAD2L2 also colocalized in the nucleus of Hela
      cells. Furthermore, overexpression of HCCA2 led to cell cycle arrest at G0/G1
      phase and therefore inhibited cell proliferation. Our research suggests that
      HCCA2 may play a novel role in cell cycle regulation.

PMID- 17541815
TI  - Optimizing defibrillation waveforms for ICDs.
AB  - While no simple electrical descriptor provides a good measure of defibrillation
      efficacy, the waveform parameters that most directly influence defibrillation are
      voltage and duration. Voltage is a critical parameter for defibrillation because
      its spatial derivative defines the electrical field that interacts with the
      heart. Similarly, waveform duration is a critical parameter because the shock
      interacts with the heart for the duration of the waveform. Shock energy is the
      most often cited metric of shock strength and an ICD's capacity to defibrillate,
      but it is not a direct measure of shock effectiveness. Despite the physiological
      complexities of defibrillation, a simple approach in which the heart is modeled
      as passive resistor-capacitor (RC) network has proved useful for predicting
      efficient defibrillation waveforms. The model makes two assumptions: (1) The goal
      of both a monophasic shock and the first phase of a biphasic shock is to maximize
      the voltage change in the membrane at the end of the shock for a given stored
      energy. (2) The goal of the second phase of a biphasic shock is to discharge the
      membrane back to the zero potential, removing the charge deposited by the first
      phase. This model predicts that the optimal waveform rises in an exponential
      upward curve, but such an ascending waveform is difficult to generate
      efficiently. ICDs use electronically efficient capacitive-discharge waveforms,
      which require truncation for effective defibrillation. Even with optimal
      truncation, capacitive-discharge waveforms require more voltage and energy to
      achieve the same membrane voltage than do square waves and ascending waveforms.
      In ICDs, the value of the shock output capacitance is a key intermediary in
      establishing the relationship between stored energy-the key determinant of ICD
      size-and waveform voltage as a function of time, the key determinant of
      defibrillation efficacy. The RC model predicts that, for capacitive-discharge
      waveforms, stored energy is minimized when the ICD's system time constant taus
      equals the cell membrane time constant taum, where taus is the product of the
      output capacitance and the resistance of the defibrillation pathway. Since the
      goal of phase two is to reverse the membrane charging effect of phase one, there
      is no advantage to additional waveform phases. The voltages and capacitances used
      in commercial ICDs vary widely, resulting in substantial disparities in waveform
      parameters. The development of present biphasic waveforms in the 1990s resulted
      in marked improvements in defibrillation efficacy. It is unlikely that
      substantial improvement in defibrillation efficacy will be achieved without
      radical changes in waveform design.

PMID- 17541816
TI  - Religiosity/spirituality and behavioral medicine: investigations concerning the
      integration of spirit with body.
AB  - This article introduces the special section on Religiosity/Spirituality and
      Behavioral Medicine. After brief comments on the increase in interest in this
      topic and related definition concerns, each of the five articles that comprise
      the special section is presented.

PMID- 17541817
TI  - Exploring the relationship between spirituality, coping, and pain.
AB  - There is growing recognition that persistent pain is a complex and
      multidimensional experience stemming from the interrelationship among biological,
      psychological, social, and spiritual factors. Chronic pain patients use a number
      of cognitive and behavioral strategies to cope with their pain, including
      religious/spiritual forms of coping, such as prayer, and seeking spiritual
      support to manage their pain. This article will explore the relationship between
      the experience of pain and religion/spirituality with the aim of understanding
      not only why some people rely on their faith to cope with pain, but also how
      religion/spirituality may impact the experience of pain and help or hinder the
      coping process. We will also identify future research priorities that may provide
      fruitful research in illuminating the relationship between religion/spirituality
      and pain.

PMID- 17541818
TI  - Chondroitin sulfate and keratan sulfate are the major glycosaminoglycans present
      in the adult zebrafish Danio rerio (Chordata-Cyprinidae).
AB  - The zebrafish Danio rerio (Chordata-Cyprinidae) is a model organism frequently
      used to study the functions of proteoglycans and their glycosaminoglycan (GAG)
      chains. Although several studies clearly demonstrate the participation of these
      polymers in different biological and cellular events that take place during
      embryonic development, little is known about the GAGs in adult zebrafish. In the
      present study, the total GAGs were extracted from the whole fish by proteolytic
      digestion, purified by anion-exchange chromatography and characterized by
      electrophoresis after degradation with specific enzymes and/or by high
      performance liquid chromatography (HPLC) analysis of the disaccharides. Two GAGs
      were identified: a low-molecular-weight chondroitin sulfate (CS) and keratan
      sulfate (KS), corresponding to approximately 80% and 20% of the total GAGs,
      respectively. In the fish eye, KS represents approximately 80% of total GAGs.
      Surprisingly, no heparinoid was detected, but may be present in the fish at
      concentrations lower than the limit of the method used. HPLC of the disaccharides
      formed after chondroitin AC or ABC lyase degradation revealed that the zebrafish
      CS is composed by DeltaUA-1-->3-GalNAc(4SO4) (59.4%), DeltaUA-1-->3-GalNAc(6SO4)
      (23.1%), and DeltaUA-1-->3-GalNAc (17.5%) disaccharide units. No disulfated
      disaccharides were detected. Immunolocalization on sections from zebrafish retina
      using monoclonal antibodies against CS4- or 6-sulfate showed that in the retina
      these GAGs are restricted to the outer and inner plexiform layers. This is the
      first report showing the presence of KS in zebrafish eye, and the structural
      characterization of CS and its localization in the zebrafish retina. Detailed
      information about the structure and tissue localization of GAGs is important to
      understand the functions of these polymers in this model organism.

PMID- 17541819
TI  - Cardioprotection in stunned and hibernating myocardium.
AB  - Although myocardial ischemia was once thought to result in irreversible cellular
      damage, it is now demonstrated that in cardiac tissue, submitted to the stress of
      oxygen and substrate deprivation, endogenous mechanisms of cell survival may be
      activated. These molecular mechanisms result in physiological conditions of
      adaptation to ischemia, known as myocardial stunning and hibernation. These
      conditions result from a switch in gene and protein expression, which sustains
      cardiac cell survival in a context of oxygen deprivation and during the stress of
      reperfusion. The pattern of cell survival elicited by ischemia in myocardial
      stunning or hibernation results in the activation of cytoprotective mechanisms
      that will protect the heart against further ischemic damage, a condition referred
      to as ischemic preconditioning. The basic mechanisms underlying stunning and
      hibernation are still a matter of intense research, which includes the discovery
      and characterization of novel survival genes not described in the heart before,
      or the unraveling of new cellular processes, such as autophagy. Understanding how
      the molecular adaptation of the cardiac myocyte during stress sustains its
      survival in these conditions therefore might help defining novel mechanisms of
      endogenous myocardial salvage, in order to expand the conditions of maintained
      cellular viability and functional salvage of the ischemic myocardium.

PMID- 17541820
TI  - The late phase of preconditioning and its natural clinical application--gene
      therapy.
AB  - There is little doubt that the discovery of ischemic preconditioning (PC) has
      been one of the fundamental milestones in the field of ischemic biology in the
      past 20 years. The purpose of this article is to review the pathophysiology and
      molecular basis of the late phase of myocardial PC. The exploitation of late PC
      for the development of novel gene therapy strategies aimed at inducing a
      permanently preconditioned cardiac phenotype (prophylactic cardioprotection) will
      also be discussed. Deciphering the mechanism of late PC has not only conceptual
      interest but also a considerable therapeutic implications, since transfer of the
      genes that underlie late PC would be expected to replicate the salubrious effects
      of this response of the heart to stress.

PMID- 17541821
TI  - Myocardial protection in man--from research concept to clinical practice.
AB  - Myocardial protection aims at preventing myocardial tissue loss: (a) In the acute
      stage, i.e., during primary angioplasty in acute myocardial infarction. In this
      setup, the attenuation of reperfusion injury is the main target. As a
      "mechanical" means, post-conditioning has already been tried in man with
      encouraging results. Pharmacologic interventions that could be of promise are
      statins, insulin, peptide hormones, including erythropoietin, fibroblast growth
      factor, and many others. (b) The patient with chronic coronary artery disease
      offers another paradigm, with the target of avoidance of further myocyte loss
      through apoptosis and inflammation. Various pharmacologic agents may prove useful
      in this context, together with exercise and "mechanical" improvement of cardiac
      function with attenuation of myocardial stretch, which by itself is a noxious
      influence. A continuous effort toward acute and chronically preserving myocardial
      integrity is a concept concerning both the researcher and the clinician.

PMID- 17541823
TI  - Newer mechanical devices in the management of acute heart failure.
AB  - Heart Failure is the only cardiovascular disease diagnosis increasing in
      prevalence in the United States. Currently there are more than 5 million people
      diagnosed with heart failure in the United States and that population is
      increasing exponentially. Clinical trials in advanced pharmacological therapies
      have shown a significant value in reducing the morbidity and mortality of the
      disease process. Nevertheless, many patients who are optimally treated with drug
      therapy continue to progress from asymptomatic left ventricular dysfunction to
      symptomatic and then end-stage heart failure. Beyond drug therapy, devices have
      begun to make a significant impact on symptoms and clinical outcomes in patients,
      particularly those with more advanced forms of heart failure. New technologies
      being investigated include destination and bridge LV assist devices. Due to the
      invasive nature of these devices a new generation of "less invasive" percutaneous
      devices are now being studied. These new generation devices offer the promise of
      improved LV function and an enhanced neurohormonal profile for the failing
      ventricle, thus improving the quality of life in the ever-burgeoning heart
      failure population.

PMID- 17541822
TI  - Reperfusion injury salvage kinase signalling: taking a RISK for cardioprotection.
AB  - Following an acute myocardial infarction (AMI), early coronary artery reperfusion
      remains the most effective means of limiting the eventual infarct size. The
      resultant left ventricular systolic function is a critical determinant of the
      patient's clinical outcome. Despite current myocardial reperfusion strategies and
      ancillary antithrombotic and antiplatelet therapies, the morbidity and mortality
      of an AMI remain significant, with the number of patients developing cardiac
      failure increasing, necessitating the development of novel strategies for
      cardioprotection which can be applied at the time of myocardial reperfusion to
      reduce myocardial infarct size. In this regard, the Reperfusion Injury Salvage
      Kinase (RISK) Pathway, the term given to a group of pro-survival protein kinases
      (including Akt and Erk1/2), which confer powerful cardioprotection, when
      activated specifically at the time of myocardial reperfusion, provides an
      amenable pharmacological target for cardioprotection. Preclinical studies have
      demonstrated that an increasing number of agents including insulin,
      erythropoietin, adipocytokines, adenosine, volatile anesthetics natriuretic
      peptides and 'statins', when administered specifically at the time of myocardial
      reperfusion, reduce myocardial infarct size through the activation of the RISK
      pathway. This recruits various survival pathways that include the inhibition of
      mitochondrial permeability transition pore opening. Interestingly, the RISK
      pathway is also recruited by the cardioprotective phenomena of ischemic
      preconditioning (IPC) and postconditioning (IPost), enabling the use of
      pharmacological agents which target the RISK pathway, to be used at the time of
      myocardial reperfusion, as pharmacological mimetics of IPC and IPost. This
      article reviews the origins and evolution of the RISK pathway, as part of a
      potential common cardioprotective pathway, which can be activated by an ever
      expanding list of agents administered at the time of myocardial reperfusion, as
      well as by IPC and IPost. Preliminary clinical studies have demonstrated
      myocardial protection with several of these pharmacological activators of the
      RISK pathway in AMI patients undergoing PCI. Through the use of appropriately
      designed clinical trials, guided by the wealth of existing preclinical data, the
      administration of pharmacological agents which are known to activate the RISK
      pathway, when applied as adjuvant therapy to current myocardial reperfusion
      strategies for patients presenting with an AMI, should lead to improved clinical
      outcomes in this patient group.

PMID- 17541824
TI  - Mycorrhizal fungi and ectomycorrhiza associated bacteria isolated from an
      industrial desert soil protect pine seedlings against Cd(II) impact.
AB  - Effects of mycorrhization with Amanita rubescens or Hebeloma sinapizans and dual
      inoculation with the fungi and ectomycorrhiza associated bacteria (EMAB)
      Pseudomonas putida or Bacillus cereus on seedling growth and accumulation of
      Cd(II) in Pinus sylvestris were studied. Both fungal and bacterial species were
      isolated from roots of pines growing in an industrial area polluted with high
      concentrations of heavy metals. During mycorrhization, A. rubescens colonized
      higher number of pine seedlings than H. sinapizans, especially when EMAB were co
      inoculated. In addition, the seedling biometric characteristics (i.e. root and
      shoot lengths and biomass) were stimulated by treatment with the fungal species
      alone and dual inoculation with the fungi and EMAB. Amanita rubescens was more
      efficient in this stimulation than H. sinapizans. The increased growth of pine
      seedlings was especially seen for co-inoculation with P. putida. Furthermore,
      elevated accumulation of Cd(II), ranging from 56 microg g(-1) to 72 microg g(-1)
      dry weight, in underground parts of the inoculated seedlings was found. The
      seedlings treated with A. rubescens accumulated higher concentrations of the
      metal than those inoculated with H. sinapizans. Additional treatment of pine
      seedlings with P. putida resulted in the higher accumulation of Cd(II) in the
      roots as compared with those inoculated with B. cereus. The results suggest that
      the growth of pine seedlings in Cd(II)-polluted soil may depend on fungal species
      forming ectomycorrhizae, species-specific co-inoculation with EMAB and
      specificity of fungal-EMAB interactions.

PMID- 17541825
TI  - Physiology driven adaptivity for the numerical solution of the bidomain
      equations.
AB  - Previous work [Whiteley, J. P. IEEE Trans. Biomed. Eng. 53:2139-2147, 2006]
      derived a stable, semi-implicit numerical scheme for solving the bidomain
      equations. This scheme allows the timestep used when solving the bidomain
      equations numerically to be chosen by accuracy considerations rather than
      stability considerations. In this study we modify this scheme to allow an
      adaptive numerical solution in both time and space. The spatial mesh size is
      determined by the gradient of the transmembrane and extracellular potentials
      while the timestep is determined by the values of: (i) the fast sodium current;
      and (ii) the calcium release from junctional sarcoplasmic reticulum to myoplasm
      current. For two-dimensional simulations presented here, combining the numerical
      algorithm in the paper cited above with the adaptive algorithm presented here
      leads to an increase in computational efficiency by a factor of around 250 over
      previous work, together with significantly less computational memory being
      required. The speedup for three-dimensional simulations is likely to be more
      impressive.

PMID- 17541826
TI  - High-frequency oscillations detected in epileptic networks using swarmed neural
      network features.
AB  - Localizing epileptic networks is a central challenge in guiding epilepsy surgery,
      deploying antiepileptic devices, and elucidating mechanisms underlying seizure
      generation. Recent work from our group and others suggests that high-frequency
      epileptic oscillations (HFEOs) arise from brain regions constituting epileptic
      networks, and may be important to seizure generation. HFEOs are brief 50-500 Hz
      pathologic events measured in intracranial field and unit recordings in patients
      with refractory epilepsy. They are challenging to detect due to low signal to
      noise ratio, and because they occur in multiple channels with great frequency.
      Their morphology is also variable and changes with distance from intracranial
      electrode contacts, which are sparsely placed for patient safety. Thus reliable,
      automated methods to detect HFEOs are required to localize and track seizure
      generation in epileptic networks. We present a novel method for mapping the
      temporal evolution of these oscillations in human epileptic networks. The
      technique combines a particle swarm optimization algorithm with a neural network
      to create features that robustly detect and track HFEOs in human intracranial EEG
      (IEEG) recordings. We demonstrate the algorithm's performance on IEEG data from
      six patients, one pediatric and five adult, and compare it to an existing method
      for detecting high-frequency oscillations.

PMID- 17541827
TI  - Critical Time Intervention: an empirically supported model for preventing
      homelessness in high risk groups.
AB  - Critical Time Intervention (CTI) is designed to prevent recurrent homelessness
      among persons with severe mental illness by enhancing continuity of care during
      the transition from institutional to community living. After providing the
      background and rationale of CTI, we describe the elements of the model and
      summarize the status of existing research on its effectiveness. We then briefly
      illustrate how the CTI model has begun to be adapted and implemented by providing
      a case example of a homeless woman's transition from shelter to housing. Finally,
      we consider plans for the further adaptation, testing and dissemination of CTI in
      other populations and service delivery settings.

PMID- 17541828
TI  - Outcomes of a life skills intervention for homeless adults with mental illness.
AB  - A manualized life skills intervention based on empowerment theory and situated
      learning was tested on 51 homeless adults with mental illness living in emergency
      or single room occupancy housing. The intervention improved skills in food,
      money, room, and self-care management and safe community participation.
      Participation included baseline measures with intervention post-tests and three
      and six month follow up measures. Comparisons were made to examine effectiveness
      between modules. There were significant improvements over time for the room and
      self-care and safe community participation modules, whereas the other modules did
      not reach statistical significance. The results suggest that through intervention
      this population may develop and retain the life skills needed to maintain
      residential stability.

PMID- 17541829
TI  - Evidence for maternal inheritance of mitochondrial DNA in allotetraploid.
AB  - The complete mitochondrial DNA (mtDNA) sequences of the allotetraploid and red
      crucian carp were determined in this paper. We compared the complete mtDNA
      sequences between the allotetraploid and its female parent red crucian carp, and
      between the allotetraploid and its male parent common carp. The results indicated
      that the complete mtDNA nucleotide identity (99.7%) between the allotetraploid
      and its female parent red crucian carp was higher than that (89.0%) between the
      allotetraploid and its male parent common carp. Moreover, the analysis on the
      start and stop codons, overlaps and spacers, and phylogeny of the mt genomes
      indicated the genetic relationship between the allotetraploid and its female
      parent red crucian carp was closer than that between the allotetraploid and its
      male parent common carp. Our results indicated that the allotetraploid mt genome
      was strictly maternally inherited. Through maternal inheritance, the mt genome in
      the F(11) allotetraploid displayed extremely high similarity to that in the
      female parent red crucian carp after 11 generations (from F(1) to F(11) hybrids).
      Such results indicated that the F(11) allotetraploid possessed the stable
      inheritance characteristic. Thus the tetraploid stocks possessed the good base to
      form a new tetraploid species in the future. Since the establishment of the new
      tetraploid stocks has the great significance in analyzing evolutionary theory of
      vertebrate and in improving aquaculture industry, analysis of the mt genome and
      the elucidation of the variation of the mt genome in the allotetraploid and its
      parents proved that it was a useful genetic marker to monitor the variations in
      the progeny of the crosses.

PMID- 17541830
TI  - Molecular characterization, expression and mapping of porcine LMP2 and MECL-1
      genes.
AB  - Low molecular mass polypeptides 2 (LMP2) and Multicatalytic endopeptidase complex
      subunit (MECL-1) are two of three catalytic beta-type subunits of the 20s
      proteasome and upon interferon gamma-induction. LMP2 is critical for the
      production of major histocompatibility complex (MHC) class I ligand and T
      lymphocytes. The LMP2 gene is located in the MHC region, but MECL-1 is located
      outside the MHC region. They are involved in the antigen presentation and are
      important candidate genes for an initial exploration of relationships between the
      antigen processing genes and disease resistance. In this report, the porcine LMP2
      and MECL-1 cDNA were cloned and A 5099 bp LMP2 genomic DNA structure was
      identified, then two single nucleotide polymorphisms were detected in the exon2
      and exon5 of LMP2 gene in 367 individuals. The LMP2 and MECL-1 genes putative
      protein included 219,274 amino acids, respectively. Alignment and phylogenetic of
      predicted porcine LMP2 and MECL-1 amino acid sequence with their homologies were
      analyzed. Tissues expression of LMP2 and MECL-1 mRNA were observed by real time
      quantitative PCR (Q-PCR) method, the results revealed MECL-1 expressed widely in
      all tissues, but LMP2 was not detected in muscle. The porcine MECL-1 gene was
      mapped to chromosome 6, closely linked to microsatellite SW1108 (LOD = 4.09,
      84cR) by radiation hybrid panel.

PMID- 17541831
TI  - The cloning and sequencing of the UDP-galactose 4-epimerase gene (galE) from
      Avibacterium paragallinarum.
AB  - The putative uridine diphosphate (UDP)-galactose 4-epimerase encoding gene, galE,
      was isolated from Avibacterium paragallinarum with the use of degenerate primers,
      colony hybridization and inverse PCR. The data revealed an open reading frame of
      1017 bp encoding a protein of 338 amino acids with a molecular weight of 37 kDa
      and an isoelectric point of 5.5. High sequence homology was obtained with an 87,
      91 and 89% sequence identity on protein level towards the galE genes from
      Actinobacillus pleuropneumoniae, Haemophilus influenza and Pasteurella multocida,
      respectively. To verify that the cloned galE gene encodes for a UDP-galactose 4
      epimeras, this gene was cloned into the pYES-2 expression vector, followed by
      transformation in a Saccharomyces cerevisiae gal10 deletion strain.
      Complementation of the gal10 deletion mutant with the galE gene confirmed that
      this gene encodes a UDP-galactose 4-epimerase.

PMID- 17541832
TI  - Comprehensive analysis of prokaryotic mechanosensation genes: their
      characteristics in codon usage.
AB  - In the present study, we examined GC nucleotide composition, relative synonymous
      codon usage (RSCU), effective number of codons (ENC), codon adaptation index
      (CAI) and gene length for 308 prokaryotic mechanosensitive ion channel (MSC)
      genes from six evolutionary groups: Euryarchaeota, Actinobacteria,
      Alphaproteobacteria, Betaproteobacteria, Firmicutes, and Gammaproteobacteria.
      Results showed that: (1) a wide variation of overrepresentation of nucleotides
      exists in the MSC genes; (2) codon usage bias varies considerably among the MSC
      genes; (3) both nucleotide constraint and gene length play an important role in
      shaping codon usage of the bacterial MSC genes; and (4) synonymous codon usage of
      prokaryotic MSC genes is phylogenetically conserved. Knowledge of codon usage in
      prokaryotic MSC genes may benefit from the study of the MSC genes in eukaryotes
      in which few MSC genes have been identified and functionally analysed.

PMID- 17541833
TI  - Molecular cloning and expression pattern of myostatin gene in yellow catfish
      (Pelteobagrus fulvidraco).
AB  - Myostatin (Mstn), a member of transforming growth factor beta (TGF-beta)
      superfamily, plays crucial roles in negative regulation of muscle growth. Yellow
      catfish, Pelteobagrus fulvidraco Richardson, is one of the most important
      freshwater aquaculture species in China, but little is known about its genes
      relate to growth. Here we report molecular cloning and expression pattern of Mstn
      gene in yellow catfish. Our results reveal that yellow catfish Mstn comprises
      three exons encoding a protein of 393 amino acid residues. Protein sequence
      alignments show that the Mstn exhibits 94% amino acid identity with other catfish
      Mstn and 59.3% identity with cattle Mstn, respectively. Moreover, the predicted
      bioactive form of yellow catfish Mstn shares 100% identity with other catfish and
      87.1% identity with cattle Mstn respectively. Employing reverse transcription
      polymerase chain reaction (RT-PCR) analysis, we demonstrated that the yellow
      catfish Mstn gene is expressed in a variety of tissues with varied levels.

PMID- 17541834
TI  - Unusual organization associated to a tandem of IS231 may yield two peculiar
      cloverleaf secondary structures.
AB  - A 5.7-kb EcoRI fragment was cloned from plasmid DNA of Bacillus thuringiensis
      strain M15. It contains two insertion sequences (IS), IS231M2 and -M1 in the 5'
      3' order, arranged in tandem, in same orientation, separated by a 540-bp region.
      The primary structure is typical of a composite transposon, here of 3847 bp in
      length, for which the name Tn231M is proposed. Each IS is delimited by 18-bp
      inverted repeats (IR), and flanked by 11-bp direct repeats (DR). Both IS share
      99.3% nucleotide identities. IS231M1 has a single open reading frame (ORF) which
      encodes a putative 477-amino-acid transposase. IS231M2 has two smaller ORFs: ORF1
      and ORF2, which could code for polypeptides of 329 and 118 amino acids in length,
      respectively. Further analysis reveals that the regions upstream of IS231M2, and
      downstream of -M1, and the 540-bp region, contain additional pairs of IR and DR.
      Interestingly, potential annealing between all pairs of IR and DR could generate
      two unusual cloverleaf secondary structures.

PMID- 17541835
TI  - Complete mitochondrial genome of the rabbitfish Siganus fuscescens (Perciformes,
      Siganidae).
AB  - We determined the complete nucleotide sequence of the mitochondrial genome for
      the rabbitfish Siganus fuscescens (Perciformes, Siganidae). This mitochondrial
      genome, consisting of 16,491 base pairs (bp), included 13 protein-coding genes, 2
      ribosomal RNAs, 22 transfer RNAs, and a noncoding control region similar those
      found in other vertebrates; the gene order was identical to that of typical
      vertebrates. Most of the genes of S. fuscescens were encoded on the H-strand,
      while the ND6 and eight tRNA (Gln, Ala, Asn, Cys, Tyr, Ser [UCN], Glu, and Pro)
      genes were encoded on the L-strand. The reading frames of ATPase 8 and 6 and
      those of ND4L and ND4 overlapped by ten and seven nucleotides, respectively. All
      mitochondrial protein-coding genes began with an ATG start codon, except for CO1,
      which started with GTG. Open reading frames of S. fuscescens ended with TAA (ND1,
      CO1, ATPase 8, ND4L, ND5 and ND6), and the remainder had incomplete stop codons,
      either TA (ATPase 6 and CO3) or T (ND2, CO2, ND3, ND4, and Cytb). The origin of L
      strand replication in S. fuscescens was located in a cluster of five tRNA genes
      (WANCY) and was 34 nucleotides in length. A major noncoding region between the
      tRNA-Pro and tRNA-Phe genes (828 bp) was considered to be the control region (D
      loop). Within this sequence, we identified a conserved sequence block
      characteristic of this region. The rabbitfish was grouped with Siganus
      canaliculatus in most parsimony analyses, which showed 100% bootstrap support for
      their divergence. These findings are useful for inferring phylogenetic
      relationships and identification within the suborder Acanthuroidei.

PMID- 17541836
TI  - Molecular cloning and sequence analysis of lamB encoding outer membrane maltose
      inducible porin of Aeromonas hydrophila.
AB  - Aeromonas hydrophila is a significantly important pathogen causing major diseases
      in humans and fresh water fish. The outer membrane proteins (OMP) which are
      strong immunogens have been reported to act as adhesins aiding in the attachment
      of enteropathogenic bacteria. It is of interest to investigate the role of OMP in
      pathogenesis and their potential as vaccine candidates. In our laboratory, we
      cloned the gene encoding channel protein LamB porin of A. hydrophila. DNA
      sequence analysis revealed a full length gene of 1345 bp having a high level of
      homology with the lamB gene of different bacteria. Open reading frame of A.
      hydrophila lamB consists of a signal peptide of 25 amino acids, two protein
      translation start sites ATG present at the 31st and 37th base pairs, a
      translation termination codon, TAA at 1333rd base pair.

PMID- 17541837
TI  - Molecular cloning and characterization of Rab6 gene in duck.
AB  - Rab (ras-like in rat brain) proteins are small GTP-binding proteins that belong
      to largest subfamily in the small G protein, which are important for molecular
      modulation of membrane in the vesicular trafficking pathways. We have cloned and
      sequenced full length cDNA of Rab6 gene in duck. The cDNA sequence consists of
      761 nucleotides and contains a complete open reading frame (ORF) of 627
      nucleotides; the putative protein includes 208 amino acids. The CDS of duck Rab6
      gene shares 86.1-90.0% homology with house mouse, silurana tropicalis, dog, human
      and orangutan, which indicates the Rab6 gene is high evolutional conservation in
      above animals.

PMID- 17541838
TI  - Molecular cloning and characterization of a novel splice variant of human ZNF300
      gene, which expressed highly in testis.
AB  - Zinc finger protein, one of the most important transcription factors, plays an
      essential role in regulating gene expression. C(2)H(2) type zinc protein with
      KRAB domain contains two parts, one is C(2)H(2) zinc finger motif which is use to
      binding to the DNA, while the other is KRAB associated box which mostly performs
      as a transcription repressor. In this study, we report the cloning and
      characterization of a novel splice variant of the human ZNF300 gene (ZNF300-B).
      The ZNF300-B gene cDNA is 2293 bp in length, encoding a putative protein with 619
      amino acid residues. ZNF300-B gene is mapped to chromosome 5q32-5q33 with seven
      exons. Reverse transcription polymerase chain reaction (RT-PCR) analysis showed
      that ZNF300-B and ZNF-300 were expressed highly in human testis.

PMID- 17541839
TI  - Molecular cloning and characterization of Crmdr1, a novel MDR-type ABC
      transporter gene from Catharanthus roseus.
AB  - A novel gene encoding a MDR-like ABC transporter protein was cloned from
      Catharanthus roseus, a medicinal plant with more than 120 kinds of secondary
      metabolites, through rapid amplification of cDNA ends (RACE). This gene (named as
      Crmdr1; GenBank accession no.: DQ660356) had a total length of 4395 bp with an
      open reading frame of 3801 bp, and encoded a predicted polypeptide of 1266 amino
      acids with a molecular weight of 137.1 kDa. The CrMDR1 protein shared 59.8, 62.5,
      60.0 and 58.2% identity with other MDR proteins isolated from Arabidopsis
      thaliana (AAD31576), Coptis japonica (CjMDR), Gossypium hirsutum (GhMDR) and
      Triticum aestivum (TaMDR) at amino acid level, respectively. Southern blot
      analysis showed that Crmdr1 was a low-copy gene. Expression pattern analysis
      revealed that Crmdr1 constitutively expressed in the root, stem and leaf, but
      with lower expression in leaf. The domains analysis showed that CrMDR1 protein
      possessed two transmembrane domains (TMDs) and two nucleotide binding domains
      (NBDs) arranging in "TMD1-NBD1-TMD2-NBD2" direction, which is consistent with
      other MDR transporters. Within NBDs three characteristic motifs common to all ABC
      transporters, "Walker A", "Walker B" and C motif, were found. These results
      indicate that CrMDR1 is a MDR-like ABC transporter protein that may be involved
      in the transport and accumulation of secondary metabolites.

PMID- 17541840
TI  - Sustained-release self-dissolving micropiles for percutaneous absorption of
      insulin in mice.
AB  - Microparticles-adsorbed insulin and zinc insulin (PenfilN) were molded to self
      dissolving micropiles (SDMPs) with chondroitin sulfate as the base for the
      percutaneous administration of insulin. Porous silicon dioxide (Sylysia 320, 440
      and 730) and porous calcium silicate (FloriteRE) were used as microparticles. As
      a reference, insulin loaded SDMPs were prepared. SDMPs were percutaneously
      administered to mice at the insulin dose level of 2.5 IU/kg. After the insertion
      of SDMPs to mouse skin, blood samples were collected for 8 h and plasma glucose
      levels were measured. There were not significant differences on minimum plasma
      glucose levels between the test preparations. However, T(mins), the time when the
      minimum glucose level appeared were 1.5 +/- 0.2 h (Sylysia 320), 1.3 +/- 0.2 h
      (Sylysia 440), 1.6 +/- 0.4 h (Sylysia 730), 2.1 +/- 0.3 h (Florite) and 1.7 +/-
      0.3 h (zinc insulin) which were greater than insulin SDMP, 0.8 +/- 0.1 h. In
      addition, greater hypoglycemic effects were observed with SDMPs containing
      adsorbent-insulin and/or zinc insulin than insulin SDMP. The mean AACs (area
      above the plasma glucose level vs. time curve) of SDMPs containing adsorbent
      insulin and zinc insulin were 357.8% h for FloriteRE, 333.1% h for Sylysia 320,
      308.1% h for Sylysia 440, 328.1% h for Sylysia 730, and 374.7% h for zinc
      insulin, respectively, which were about two folds higher than that of insulin
      SDMN, 161.2% h. Those results suggest the usefulness of SDMPs composed of
      adsorbent-insulin as a long-acting percutaneous insulin preparation.

PMID- 17541841
TI  - Design and evaluation of a chitosan-aprotinin conjugate for the peroral delivery
      of therapeutic peptides and proteins susceptible to enzymatic degradation.
AB  - One main barrier for the peroral administration of therapeutic peptides and
      proteins is the enzymatic barrier, that is mediated by luminally secreted and
      membrane bound proteolytic enzymes. It was the aim of the study to synthesise,
      characterise and evaluate a novel polymer-inhibitor conjugate in order to improve
      the bioavailability of orally-administered peptides and proteins. The
      trypsin/chymotrypsin inhibitor aprotinin was covalently bound to chitosan. The
      percentage of the inhibitor in the polymer-inhibitor conjugate (m/m) was
      determined to be between 1.11 +/- 0.36 and 1.92 +/- 0.05%. In vitro enzyme assays
      clearly demonstrated the potential of the novel conjugate to inhibit trypsin and
      chymotrypsin. Moreover, studies in rats were performed to evaluate the efficacy
      of the conjugate in vivo. Eight hours after oral administration of tablets
      containing insulin and the novel chitosan-aprotinin conjugate, the mean blood
      glucose level decreased to 84 +/- 6%. In contrast, the mean blood glucose level
      in the control group increased to 121 +/- 8% of the initial measured blood
      glucose level. In conclusion it was demonstrated that chitosan-aprotinin
      conjugate represents a novel and promising tool for the oral administration of
      therapeutic peptides and proteins susceptible to enzymatic degradation caused by
      trypsin and chymotrypsin.

PMID- 17541842
TI  - Characteristics and anti-proliferative activity of azelaic acid and its
      derivatives entrapped in bilayer vesicles in cancer cell lines.
AB  - The hydrophilicity and lipophilicity of azelaic acid (AA) were modified to
      diethyl azelate (DA) which was synthesized by Fisher esterification reaction and
      identified by IR, MS and (1)H NMR and to azelaic acid-beta-cyclodextrin complex
      (AACD) which was prepared by inclusion complexation and identified by IR, DSC and
      XRD respectively. AA, DA and AACD were entrapped in liposomes and niosomes
      comprising of L-alpha-dipalmitoyl phosphatidylcholine (DPPC)/cholesterol at 7:3
      molar ratio and Tween61/cholesterol at 1:1 molar ratio, respectively, using a
      thin-film hydration method with sonication. The size and morphology of these
      bilayer vesicles were determined by optical and transmission electron microscopy.
      The particle size was found to be in the range of 90-190 nm. The entrapment
      efficiency of AA, DA and AACD in all vesicular formulations was more than 80%, as
      analyzed by HPLC for AA and AACD, and GC for DA. Anti-proliferative activity of
      AA and its derivatives (DA and AACD) both entrapped and not entrapped in bilayer
      vesicles, using MTT assay in three cancer cell lines (HeLa, KB and B(16)F(10))
      comparing with vincristine, were investigated. AACD showed the highest potency
      comparing to AA in HeLa, KB and B(16)F(10) of 1.48, 1.6 and 1.5 times,
      respectively. AA entrapped in liposomes was about 90 times more potent than the
      free AA, and about 1.5 times less potent than vincristine. When entrapped in
      bilayer vesicles, DA and AACD were more effective than AA in killing cancer
      cells. AACD entrapped in liposomes gave the highest anti-proliferation activity
      in HeLa cell lines with the IC(50) of 2.3 and 327 times more potent than
      vincristine and AA, respectively. DA in liposomes demonstrated the IC(50) of 0.03
      times less potent than vincristine in KB cell lines, while in B(16)F(10) AACD in
      niosomes showed the IC(50) of 0.05 times less potent than vincristine. This study
      has suggested that the modification of AA by derivatization and complexation as
      well as the entrapment in bilayer vesicles can enhance its therapeutic efficacy.

PMID- 17541843
TI  - Targeting of biotinylated oligonucleotides to prostate tumors with antibody-based
      delivery vehicles.
AB  - Specific delivery of therapeutic agents to tumor sites remains a problem and
      requires a nontoxic carrier able to bind a specific tumor cell marker. Although
      antibodies have been utilized as protein carriers for different types of drugs,
      they have not been employed for delivery of antisense oligonucleotides (ODNs). In
      this study, we modified monoclonal antibodies to target biotinylated ODNs to
      prostatic tumors which express prostate specific antigen (PSA) and prostate
      specific membrane antigen (PSMA). Modified antibodies retained immunoreactivity
      and demonstrated an ability to form complexes with ODNs. Biodistribution of (35)S
      oligonucleotide-antibody complexes was also examined in nude mice bearing human
      derived LNCaP prostatic tumors. Delivering ODNs with modified prostate specific
      antibodies produced greater tissue uptake and higher blood levels with both PSA
      and PSMA directed antibodies. While tumor uptake was not significantly improved
      after 24 h, the overall results of this study provide some additional insights
      into the complexity of the antibody-mediated delivery of ODNs in vivo. The
      strategies employed here for the selective delivery of ODNs warrant further
      investigation.

PMID- 17541844
TI  - In vivo transfection rat small intestine K-cell with pGIP/Ins plasmid by DOTAP
      liposome.
AB  - Gene therapies to produce insulin in diabetic patients have been considered for
      several years. Genetic engineering of ectopic insulin production and secretion in
      autologous non-beta-cells has been tested in different tissues. Recently, gut K
      cells have been shown to express glucokinase, the glucose sensor of pancreatic
      beta-cells. K-cells are responsible for the secretion of the glucose-dependent
      insulinotropic peptide (GIP). Transfection of K-cells by a specific plasmid to
      produce insulin correlated to glucose level is being considered. Cationic
      liposomes are non-viral gene delivery to lung, spleen, liver and intestinal
      cells. DOTAP-GIP/Ins plasmid complex was used for transfection of K-cells in
      vivo. RT-PCR assay of human insulin mRNA revealed that the transfection of
      insulin gene by DOTAP liposome is an efficient tool. The genetic engineering of
      ectopic insulin production and secretion in autologous non-beta-cells is an
      appropriate method. The potential of the transmission of a constructed plasmid,
      which contains human insulin gene under the control of GIP promoter, to gut K
      cells could be considered for treatment of diabetes.

PMID- 17541845
TI  - Effect of iNOS and NF-kappaB gene silencing on beta-cell survival and function.
AB  - PURPOSE: Type I diabetes results from beta-cell death and dysfunction, induced by
      infiltration of immune cells and local production of inflammatory cytokines.
      Therefore, we investigated the effect of iNOS and NF-kappaB gene silencing on
      beta-cell survival and function. METHODS: Rat insulinoma INS-1E cells were
      transfected with chemically synthesized siRNA after complex formation with
      Lipofectamine 2000. Cells were then treated with a cocktail of inflammatory
      cytokines (IL-1beta+ TNF-alpha+ IFN-alpha), and glucose stimulated-insulin
      response and viability were determined. iNOS and NF-kappaB gene expression was
      assessed at mRNA level by real time RT-PCR. The effect of gene silencing was also
      correlated with cytokine-induced NO production and apoptosis. RESULTS:
      Transfection of INS-1E cells with siRNAs silenced iNOS and NF-kappaB gene
      expression and reduced NO production in a sequence-specific manner without
      causing significant loss of cell viability and function. However, the abrogation
      of NO production did not prevent INS-1E cells from cytokine-induced apoptosis,
      suggesting that this event may not be totally dependent on NO production.
      CONCLUSION: The gene silencing approach presented here is capable of attenuating
      the effects of inflammatory cytokines, such as iNOS expression and NO production
      and it will help to identify new target genes to improve islet transplantation.

PMID- 17541846
TI  - Evaluation of effect of ephedrine on the transport of drugs from the nasal cavity
      to the systemic circulation and the central nervous system.
AB  - It has been shown that vasoconstrictive drugs such as ephedrine derivatives are
      able to decrease systemic absorption of drugs administered by mucosal surfaces.
      The present paper set out to evaluate in the rat model the effect of co
      administered nasal ephedrine on the absorption of GR138950 in a simple and in a
      pectin self-gelling formulation. It was hypothetised that a decrease in nasal
      systemic absorption would lead to an increase in direct nose-to-brain transport
      as demonstrated by the drug concentration in the olfactory lobes of the brain. It
      was found that ephedrine administered nasally with the drug in a simple aqueous
      solution resulted in a significant increase in nasal systemic absorption and also
      an increase in brain delivery; however, this trend was not observed with the
      pectin formulations. The pectin formulation with ephedrine resulted in lower
      systemic absorption of GR138950 and lower brain uptake compared to the simple
      solution formulation containing ephedrine.

PMID- 17541847
TI  - In memoriam: Harold I. Lief, MD.

PMID- 17541848
TI  - Silent killers of the night: an exploration of psychological health and
      suicidality among female street sex workers.
AB  - This article examines factors that relate to psychological health (as measured by
      the World Health Organization Quality of Life Instrument) as well as suicide
      attempts among female street sex workers (FSSWs) in Hong Kong. On average, our
      sampled FSSWs scored significantly lower on the psychological health domain in
      comparison to the general Hong Kong female population. Factors associated with
      the working environment in the sex industry were significantly associated with
      poor psychological health and suicidality. Greater attention is needed to examine
      the physical and emotional harm intrinsic to certain occupations and the role of
      financial needs in the experience of psychological stress.

PMID- 17541849
TI  - Masturbation in the United States.
AB  - Using data from the nationally representative National Health and Social Life
      Survey, this study queried the correlates of masturbation in the United States in
      1992. Among those aged 18-60, 38% (CI, 35-41) of women and 61% (CI, 57-65) of men
      reported any masturbation over the preceding year. The system of factors
      underlying masturbation was similar for both genders, consistent with a
      convergence in gender patterns of sexual expression in the United States. Among
      both women and men, masturbation responded to a stable sexualized personality
      pattern, catalyzed by early-life factors and manifested in current sexual traits.
      Strikingly, the masturbation-partnered sex linkage, often conceptualized either
      as compensating for unsatisfying sex or complementing a satisfactory sex life,
      appeared to be bimodal for both genders. For some, masturbation complemented an
      active and pleasurable sex life, while among others, it compensated for a lack of
      partnered sex or satisfaction in sex.

PMID- 17541850
TI  - Women's relationship quality is associated with specifically penile-vaginal
      intercourse orgasm and frequency.
AB  - A growing empirical literature demonstrates that the only sexual behavior
      consistently associated with indices of better physiological and psychological
      function is the one sexual behavior relevant to potential gene propagation. In
      the present study, 30 Portuguese women reported on their frequency of different
      sexual behaviors and corresponding orgasm rates and also completed the Perceived
      Relationship Quality Components (PRQC) Inventory. As hypothesized, frequency of
      penile-vaginal intercourse correlated positively with PRQC dimensions:
      Satisfaction, Intimacy, Trust, Passion, Love (all r >/= .40) and Global
      Relationship Quality (r = .55). Noncoital sexual behaviors with a partner were
      uncorrelated with the PRQC dimensions. Masturbation frequency was inversely
      associated with Love (r = -.38). Penile-vaginal orgasmic frequency correlated
      positively with PRQC dimensions: Satisfaction, Intimacy, Passion, Love (all r >/=
      .44) and Global Relationship Quality (r = .52). Penile-vaginal intercourse
      orgasmic consistency was inversely associated with masturbation frequency. Social
      desirability scores did not confound the associations. Results are discussed in
      terms of both evolutionary and psychoanalytic theories.

PMID- 17541851
TI  - Evaluating the quality of websites offering information on female hypoactive
      sexual desire disorder.
AB  - This study evaluates websites relevant to female hypoactive sexual desire
      disorder (HSDD). Its primary aim is to evaluate the quality of Internet HSDD
      information. One hundred and one websites, identified through simple Google
      searches, were scored using a tool incorporating expert consensus-derived quality
      criteria for HSDD. The tool included structural criteria such as currency,
      authorship, and disclosure of competing interests. It also included performance
      criteria, evaluating accuracy, and comprehensiveness, and was adapted from a
      published website evaluation tool for diabetes. For each website, a quality index
      score with a potential range from 1 to 5 (1 = poor, 5 = excellent) was
      calculated, and the websites were rank ordered using this score. Quality index
      scores ranged from 1.68 to 4.64, with 75% of websites scoring at or below 3.27.
      Test-retest reliability was moderate (n = 24, r = 0.6601, P = .0004). Rank
      ordering of the websites by quality index allowed identification of the top five
      highest quality websites. The majority of HSDD websites' quality scores fell in
      the score range from 1 to 3, indicating room for improvement in the quality of
      websites that address HSDD. Website evaluation tools utilizing both structural
      and performance quality criteria may help clinicians to assist their patients in
      assessing the quality of Internet health information.

PMID- 17541852
TI  - Links among paroxetine-induced sexual dysfunctions, gender, and CYP2D6 activity.
AB  - The aim of the study was to compare the distribution of therapeutic efficacy and
      sexual dysfunction during maintenance paroxetine treatment in 17 males and 38
      females genotyped and phenotyped to determine their CYP2D6 metabolic status.
      Clinical results were monitored on scales Clinical Global Impression-Severity of
      Illness Scale (CGIS) and Arizona Sexual Experience Scale (ASEX). The phenotype
      procedure showed 7 males and 12 females with extensive metabolic status (EM) and
      10 males and 26 females with poor metabolic status (PM). No variation in
      therapeutic efficacy between male and female subjects classified as PM and those
      marked as EM was found. A significantly higher rate of sexual dysfunction (p =
      0.01) was recorded among females with a PM phenotype.

PMID- 17541853
TI  - Normal and persistent genital arousal in women: new perspectives.
AB  - Interest in women's sexual functioning has increased in recent years although the
      primary emphasis has been on deficits in both genital and subjective sexual
      response. Female sexual psychophysiology research suggests that women are capable
      of greater sexual responsiveness than previously thought and can experience
      genital response in the absence of a subjective experience of sexual arousal.
      Women who report relatively persistent genital arousal, both with and without
      accompanying distress, provide case examples of the potential for dissociation
      between genital and psychological sexual response. In this article, we provide
      case illustrations of women reporting unprovoked genital arousal both with and
      without distress and suggest that what appears to be spontaneous genital arousal
      in some women may be the result of either subconscious processing of sexual
      stimuli in the environment - stimuli that are either consciously unacceptable or
      not noticed. Finally, we suggest that there may exist three types of genital
      arousal in women: 1) spontaneous sensations of genital arousal that are appraised
      as mildly pleasurable; 2) persistent feelings of genital arousal that are
      experienced as mildly distracting but not especially unwelcome or bothersome; and
      3) continuous, intense, and persistent genital arousal that is extremely
      distracting, distressing, and worrisome. A variety of psychological,
      pharmacological, vascular, and neurological factors may account for these
      differences in women's genital arousal responsiveness. However, a full
      understanding of the range and variation in women's sexual experience remains to
      be elucidated.

PMID- 17541854
TI  - Re: Birth order in transgendered males from Polynesia: a quantitative study of
      Samoan fa'afafine.

PMID- 17541858
TI  - The structure of a web-based HIV testing belief inventory (wHITBI) for college
      students: the evidence of construct validation.
AB  - The aim of this study is to develop a web-based HIV testing belief Inventory
      (wHITBI) and to examine the reliability and validity of the scores of the
      instrument. Steps for developing the item pool are described. Students from one
      major university in the south-eastern US were recruited. The sample (n = 440) was
      randomly split into equivalent halves for an exploratory factor analysis (EFA)
      and confirmatory factor analysis (CFA). The EFA showed that the wHITBI items were
      loaded in a way consistent with the four theoretical constructs: perceived
      benefits, concerns of HIV risk, perceived stigma, and availability/accessibility.
      CFA using LISREL 8.7 confirmed the structure of the inventory indicated by good
      model-fit indices (chi(2)/d.f. = 1.79; root mean square error of approximation =
      .06; non-normed fit index = .89; comparative fit index = .90; incremental fit
      index = .91; root mean square = .07), with all factors loaded significantly (p <
      .001). The composite reliability ranged from .67 to .76. The results also showed
      that these scales can distinguish well among HIV-tested and never-tested
      students. The validated wHITBI has implications on future applications for the
      development and evaluation of HIV prevention and education programs delivered via
      the Internet.

PMID- 17541859
TI  - Computational analysis of non-adherence and non-attendance using the text of
      narrative physician notes in the electronic medical record.
AB  - Non-adherence to physician recommendations is common and is thought to lead to
      poor clinical outcomes. However, no techniques exist for a large-scale assessment
      of this phenomenon. We evaluated a computational approach that quantifies patient
      non-adherence from an analysis of the text of physician notes. Index of non
      adherence (INA) was computed based on the number of non-adherence word tags
      detected in physician notes. INA was evaluated by comparing the results to a
      manual patient record review at the individual sentence and patient level. The
      relationship between INA and frequency of Emergency Department visits was
      determined. The positive predictive value of identification of individual non
      adherence word tags was 93.3%. The Pearson correlation coefficient between the
      INA and the number of documented instances of non-adherence identified by manual
      review was 0.62. The frequency of ED visits was more than twice as high for
      patients with INA in the highest quartile (least adherent) than for patients with
      INA in the lowest (most adherent) quartile (p < 0.0001). We have described the
      design and evaluation of a novel approach that allows quantification of patient
      non-adherence with physician recommendations through an analysis of physician
      notes. This approach has been validated at several levels and demonstrated to
      correlate with clinical outcomes.

PMID- 17541860
TI  - A cost-effective add-on-value card-assisted firewall over Taiwan's NHI VPN
      framework.
AB  - Besides the overall budget for building the infrastructure of a healthcare
      service-based virtual private network (VPN) in Taiwan, two issues were considered
      critical for its acceptance by the country's 17,000 plus medical institutions.
      One was who was to pay for the network (ADSL or modem) connection fee; the other
      was who was to pay for the firewall/anti-virus software. This paper addresses the
      second issue by proposing an efficient freeware firewall, named card-assisted
      firewall (CAF), for NHI VPN edge-hosts, which is also an add-on-value application
      of the National Healthcare IC card that every insurant and medical professional
      has. The innovative concept is that any NHI VPN site (edge-host) can establish
      diversified secure-authenticated connections with other sites only by an
      authentication mechanism, which requires a NHI Java card state machine and the
      Access Control List of the host. It is different from two-factor authentication
      cards in four ways: (1) a PIN code is not a must; (2) it requires authentication
      with the remote IC card Data Centre; (3) the NHI cards are already available, no
      modification is needed, and there is no further cost for the deployment of the
      cards; (4) although the cards are in the reader, the communication cannot start
      unless the cards are in the corresponding states; i.e. the states allow
      communication. An implementation, on a Microsoft Windows XP platform,
      demonstrated the system's feasibility over an emulation of the NHI VPN framework.
      It maintained a high line speed, the driver took up 39 KB of disk space,
      installation was simple, not requiring any extra hardware or software, and the
      average packet processing time of the CAF driver measured was 0.3084 ms. The
      average overhead in comparing the Access Control List predefined routing in card,
      in an FTP testing experiment, was 5.7 micros (receiving) and 8 micros (sending).

PMID- 17541861
TI  - The value of using verbs in Medline searches.
AB  - New findings are continuously identified thanks to novel diagnostic procedures,
      among others in medical imaging. It would be useful to retrieve these new
      findings from literature. The aim of this work is to investigate if using verbs
      in MEDLINE queries can improve the retrieval of findings. Verbs used in the field
      of findings were selected: 'to show' (an examination shows a finding) and 'to
      confirm' (a finding confirms a diagnosis). For each of these verbs, semantically
      close verbs were researched on the WordNet website. Then, the extent to which
      adding these verbs to a query about various radiological pathologies can improve
      findings retrieval in Medline citations was studied. This method has been tested
      on two sets of MEDLINE citations regarding the diagnostic imaging of musculo
      skeletal disorders. Using appropriate verbs in Medline queries enhances the
      precision from 53% to 61% and from 53% to 74%, respectively, in our first and
      second test set. A recall of 74% and 83% was reached in our two experiments.
      Using relevant verbs can be a rather simple way to improve the retrieval of
      findings related to diseases and diagnostic procedures from Medline citations.

PMID- 17541862
TI  - Web-based question-answering service of a family physician -- the characteristics
      of queries in a non-commercial open forum.
AB  - The use of the Internet is growing rapidly. Up to 70% of American Internet
      surfers use the Web for some kind of medical purpose. Only a few studies
      characterized the consulting population and their inquiries. The objective of
      this study was to define the content of queries and the characteristics of the
      consulting population in an open access 'Ask the family physician' non-commercial
      open forum. Data had been collected from the family medicine forum in
      www.doctors.co.il. This site has 10 - 15 new queries daily, and a physician reply
      is given on most occasions within 24 h. We analysed demographic characteristics
      and the content of the queries. In addition, we sent detailed questionnaires to
      200 randomly selected consulters. We analysed 1,002 consecutive queries. The
      average age of the consulters was 31.8 years, 63.4% women. Women applied more
      often for someone else, compared to men (13.7 versus 8%p = 0.01). 82.2% applied
      to the forum for a first opinion on the subject matter. The most frequent
      subjects were: infectious diseases (7.3%), deciphering blood chemical analysis
      results (3.2%), vitamin B(12) (3.2%), deciphering blood count analysis results
      (2.9%), Epstein - Barr virus and Cytomegalovirus (2.8%), and hypertension (2.4%).
      Only 10% (20/200) replied to our e-mail questionnaire. We described the
      characteristics of inquiries to a Web-based question answering service. Its
      consumers are mainly younger females who consult the virtual physician prior to
      consulting their own family physician. They mainly seek medical knowledge
      especially in interpreting laboratory tests and information about various medical
      conditions.

PMID- 17541863
TI  - Biomedical information retrieval across languages.
AB  - This work presents a new dictionary-based approach to biomedical cross-language
      information retrieval (CLIR) that addresses many of the general and domain
      specific challenges in current CLIR research. Our method is based on a
      multilingual lexicon that was generated partly manually and partly automatically,
      and currently covers six European languages. It contains morphologically
      meaningful word fragments, termed subwords. Using subwords instead of entire
      words significantly reduces the number of lexical entries necessary to
      sufficiently cover a specific language and domain. Mediation between queries and
      documents is based on these subwords as well as on lists of word-n-grams that are
      generated from large monolingual corpora and constitute possible translation
      units. The translations are then sent to a standard Internet search engine. This
      process makes our approach an effective tool for searching the biomedical content
      of the World Wide Web in different languages. We evaluate this approach using the
      OHSUMED corpus, a large medical document collection, within a cross-language
      retrieval setting.

PMID- 17541864
TI  - Use of computers and the Internet by residents in US family medicine programmes.
AB  - Computers, personal digital assistants (PDA), and the Internet are widely used as
      resources in medical education and clinical care. Educators who intend to
      incorporate these resources effectively into residency education programmes can
      benefit from understanding how residents currently use these tools, their skills,
      and their preferences. The researchers sent questionnaires to 306 US family
      medicine residency programmes for all of their residents to complete. Respondents
      were 1177 residents from 125 (41%) programmes. Access to a computer was reported
      by 95% of respondents. Of these, 97% of desktop and 89% of laptop computers could
      access the Internet. Residents accessed various educational and clinical
      resources. Half felt they had 'intermediate' skills at Web searches, 23% had
      'some skills,' and 27% were 'quite skilled.' Those under 30 years of age reported
      higher skill levels. Those who experienced a Web-based curriculum in medical
      school reported higher search skills and greater success in finding clinical
      information. Respondents preferred to use technology to supplement the didactic
      sessions offered in resident teaching conferences. Favourable conditions exist in
      family medicine residency programmes to implement a blend of traditional and
      technology-based learning experiences. These conditions include residents'
      experience, skills, and preferences.

PMID- 17541865
TI  - Completeness of medical records in emergency trauma care and an IT-based strategy
      for improvement.
AB  - The medical trauma record, produced in the Accident & Emergency Departments
      (AEDs) receives much attention from both health-care professionals and parties
      interested in quality of care. While it is an important data source for health
      care professionals in their everyday work, and for quality assessment by third
      parties, the (paper) medical record is usually negatively evaluated because of
      incompleteness. In this article, we show that completeness is relative to the
      purpose for which the record is used. We distinguish two contexts in which the
      trauma record is used: the primary-care process at the AED, and assessment and
      monitoring of trauma care. Incompleteness of the medical record is valued
      differently in these contexts. Especially with regard to the information demands
      of quality assessment, and more specifically the national trauma registry, the
      work processes in the AED have not evolved sufficiently as yet. Information
      technology has great power to improve completeness and to facilitate quality
      assessment, but it cannot solve the problem of incompleteness in itself. One
      solution we propose is to restructure the recording process by introducing a
      clerk. This clerk could also be a nurse or physician who is temporarily released
      from direct patient care.

PMID- 17541866
TI  - Effect of NSAID on muscle injury and oxidative stress.
AB  - Indirect markers of muscle damage and delayed onset muscle soreness were examined
      and correlated to changes in oxidative stress, plasma antioxidant potential, and
      use or nonuse of non-steroidal anti-inflammatory drugs in 60 ultra-marathoners
      following the Western States Endurance Run. Blood was collected prior to and
      immediately following the race and analyzed for muscle damage by creatine
      phosphokinase and oxidative stress by F (2)-isoprostanes, protein carbonyls, and
      lipid hydroperoxides and antioxidant potential by the ferric reducing ability of
      plasma. Subjects recorded delayed onset muscle soreness during the week following
      the race. Lipid hydroperoxide concentrations were unchanged, but F (2)
      isoprostanes, protein carbonyls, ferric reducing ability of plasma, creatine
      phosphokinase, and delayed onset muscle soreness increased significantly
      postrace. Protein carbonyls were significantly higher postrace in nonsteroidal
      anti-inflammatory drug users versus nonusers (p < 0.05). However, there was no
      difference between users and non-users for all other markers. Postrace creatine
      phosphokinase concentrations were not correlated with oxidative stress markers
      but were correlated with changes in delayed onset muscle soreness. Based upon
      these findings, caution should be used when consuming nonsteroidal anti
      inflammatory drugs during ultra distance events.

PMID- 17541867
TI  - [Renal and cardiac functions as prognostic factors after revascularization for
      myocardial infarction].
AB  - BACKGROUND AND OBJECTIVE: In the last few decades optimal treatment of myocardial
      infarction has been achieved by thrombolytic and interventional reperfusion as
      well as subsequent secondary pharmacological prevention. It remains a subject of
      debate what factors influence prognosis after such measures. PATIENTS AND
      METHODS: 939 patients who had sustained acute myocardial infarction (75.1% males,
      aged 62.5 10.1 years) were followed prospectively after revascularization, using
      a multicenter registry (PreSCD) registry. Date and site of infarction,
      reperfusion measures, cardiovascular risk factors, hemoglobin and creatinine, QRS
      duration, ventricular arrhythmias recorded by Holter ECG monitoring were
      recorded, as well as biplane left ventricular ejection fraction (LVEF).
      Multivariate logistic Cox regression analysis was used to determine the effect of
      these various factors on overall mortality, resuscitation outcome, ventricular
      tachycardia, re-infarction, syncope and interventional or surgical
      revascularization. RESULTS: Complete data were collected on 926 patients (98.6%).
      During the follow-up period of 578 47 days there were 39 deaths (4.2%), 29 of
      them due to cardiac reasons, predominantly sudden cardiac death (58.6%). The
      occurrence of left bundle branch block was associated overall with a sevenfold
      increase in the of death (hazard ratio [95% confidence interval, (CI) 6.940
      (2.912-16.539); p<0.0001), while an increase of serum creatinine by 1 mol/l
      raised the overall mortality by 0.7% (Hazard ratio (95% CI) 1.007 (1.03-1.012);
      p<0.001]. Improvement of LVEF by 1 % was associated with a 5% reduction in
      mortality risk (Hazard ratio [95% CI] 0.946 (0.918-0.975); p<0.0001].
      Conventional cardiovascular risk factors, previous revascularization measures,
      site of infarction and pharmacological treatment failed to show any significant
      influence on end-points. CONCLUSION: In patients who had revascularization
      measures after a myocardial infarction the mortality rate was less than 5%. The
      risk of death was determined by LVEF, occurrence of left bundle branch block and
      renal failure.

PMID- 17541868
TI  - [Acute pancreatitis and duodenobiliary fistula--a rare complication of Crohn's
      disease].
AB  - HISTORY: A 53-year-old man with long-standing Crohn's disease presented with
      recurrent abdominal pain and vomiting; lipase levels were elevated.
      INVESTIGATIONS AND DIAGNOSIS: At admission ultrasound demonstrated a swollen head
      of the pancreas, dilated pancreatic and intrahepatic bile ducts and
      peripancreatic fluid. At upper gastrointestinal endoscopy a 10 mm bleeding ulcer
      was identified, which histologically proved to be epitheloid cell-containing
      granulomas. A fistula connecting to the hepatocholedochal duct was identified at
      the floor of the ulcer. Helicobacter pylori was not demonstrated. TREATMENT AND
      COURSE: After sphincterotomy of the papilla of Vater concrements were extracted
      and a stent was implanted into the common bile duct. Ultimately a total of five
      stents were consecutively implanted via the major papilla, closing the fistula.
      After three years all stents were removed and pancreatitis did not recur.
      CONCLUSION: The differential diagnosis of abdominal pain in patients with Crohn's
      disease is often difficult and should include fistulas of the upper
      gastrointestinal tract which may be treated endoscopically.

PMID- 17541869
TI  - [Molecular pathogenesis of ocular vascular disease--anti-angiogenesis as a
      therapeutic concept].
AB  - Retinopathy of prematurity, diabetic retinopathy and age-related macular
      degeneration are the most common blinding disease in the western world during
      childhood, in adults, and in the elderly patient. All three diseases have a
      vascular damage in common that leads to a pathological angiogenesis. The basic
      mechanisms include complex interactions between endothelial cells, pericytes, and
      matrix molecules. We know the "vocabulary" and try to understand the regulation
      of physiological and pathological angiogenesis. Building upon this knowledge, we
      are now, with the advent of clinically available vascular endothelial growth
      factors, for the first time able to therapeutically modulate angiogenesis.

PMID- 17541870
TI  - [Secondary sclerosing cholangitis with gallstone (following longterm ventilation
      and treatment with catecholamines)].

PMID- 17541871
TI  - [Dual platelet aggregation inhibition in coronary artery stent implantation--what
      is evidence-based?].
AB  - Dual platelet inhibition (ASA and clopidogrel) is the generally accepted standard
      therapy to avoid stent thrombosis although clopidogrel is not approved for this
      indication in Germany. The duration of dual platelet inhibition depends on the
      complexity of the stenosis, plaque activity and the type of stent implanted.
      Recent analyses suggested that implantation of drug eluting stents is associated
      with a substantially higher rate of stent thrombosis when compared with bare
      metal stents. This in turn fueled an ongoing debate about the optimal duration of
      dual platelet inhibition after implantation drug eluting stents. Guideline
      rcommendations vary between between 3 months and lifelong therapy with updates
      and additional statements published on a monthly basis leaving cardiologists and
      primary care providers in a state of therapeutic uncertainty. Taking the most
      recent guidelines and professional statements into account the following duration
      of dual platelet inhibition can be recommended: dual platelet inhibition for 1
      month after implantation of bare metal stents, dual platelet inhibition for 9-12
      months after an acute coronary syndrome; dual platelet inhibition for at least 12
      months after implantation of drug eluting stents and brachytherapy in patients
      who are not at high risk for bleeding. Patients with previously implanted drug
      eluting stents who are currently taking dual antiplatelet therapy are at high
      risk for developing stent thrombosis when a situation arises that requires
      cessation or interruption of dual platelet inhibition. Therefore, the
      interventionalist is advised to carefully discuss risks and benefits of the
      selected stent and clearly document the decision process in an accepted consent
      form. When elective or urgent surgery is required the surgeon and practitioner
      must decide whether the procedure can be performed with reasonable safety without
      discontinuation of antiplatelet therapy posing a higher bleeding risk to the
      patient. Patients on chronic oral anticoaglation should be additionally treated
      with clopidogrel for 1 month after implantation of bare metal or 12 months after
      drug-eluting stents. Additional treatment with ASS is not generally recommended
      since the bleeding risk of this triple medication may overweigh the benefits of
      dual antiplatelet inhibition.

PMID- 17541872
TI  - [Adherence to therapy in bronchial asthma].
AB  - Asthma is a chronic disease requiring regular use of controller medication (e.g.
      inhaled corticosteroids at step 2 of treatment guidelines) to improve symptoms
      and prevent exacerbations. However, inadequate patient adherence/compliance to
      prescribed treatment regimens is a major cause of poor clinical outcome.
      Adherence rates in these patients are generally about 50%. Typically, adherence
      with reliever medication is better than with controller medications. Poor
      compliance most often results in infrequent and lower than prescribed taking of
      medication. While older age or female gender are fixed factors, some modifiable
      characteristics which can achieve better adherence include formal education,
      higher socioeconomic status, belief that asthma is a serious illness, fewer
      concerns about the side effects of their medication, shortened and simple
      treatment regimens (including the prescription of inhaled fixed-combination
      devices), patient-oriented devices for inhalation therapy, and good patient
      physician relationship. There is no gold standard for quantifying patient
      adherence. In general, direct measures of assessing patient behavior, such as
      direct observation or electronic inhaler monitoring, give a more accurate, valid
      indication than indirect methods such as patient diaries, self-reporting,
      weighting of inhaler devices or doctors' judgment. An understanding of the
      barriers that impede guideline adherence, described in this article, is necessary
      before programs are designed to initiate changes in the practices of the treating
      doctor.

PMID- 17541873
TI  - [Competitive anorexia. The nosological concept of anorexia must be broadened].

PMID- 17541874
TI  - [Introduction: patient volume and treatment results in neonatology and perinatal
      medicine].

PMID- 17541875
TI  - [The relationship between patient volume and neonatal outcome].

PMID- 17541876
TI  - [Perinatal medicine 2007 in Germany--anomie despite evidence?].

PMID- 17541877
TI  - [Minimum patient volume in care for very low birthweight infants: a review of the
      literature].
AB  - BACKGROUND: Following the introduction of the DRG system and the definition of
      structural requirements for neonatal intensive care units (NICUs) in Germany, the
      number of perinatal centres has increased dramatically. The question arises if
      the formation of a great number of small NICUs compromises the outcome of infants
      with less than 1 500 g birthweight (VLBW). MATERIAL AND METHODS: A systematic
      medline search was performed for publications on patient volume in relation to
      outcome of VLBW infants. Mortality and intraventricular hemorrhage were used as
      outcome criteria. 9 publications from North America, 7 from non-German Europe and
      5 from Germany were found. In 18 studies odds ratios and 95 % confidence
      intervals were reported for volume-outcome relations. RESULTS: For VLBW infants,
      mortality and intraventricular hemorrhage rates varied greatly between hospitals.
      In 20 of 21 publications, results were significantly less favourable in smaller
      hospitals. The threshold for obstetrics was 500-1000 deliveries per year and for
      neonatology 35-50 VLBW admissions per year. No significant relation of volume and
      outcome was found above 50 VLBW infants per year. DISCUSSION: The requirement of
      a minimum patient volume is a necessary, but not the only condition for good
      results in VLBW infants. CONCLUSIONS: In addition to fulfilling formal structural
      requirements, perinatal centres should be established in large delivery hospitals
      with at least 35 to 50 VLBW admissions per year.

PMID- 17541878
TI  - [Mortality among premature newborns below 32 weeks of gestational age depending
      on level of care and patient volume in Nordrhein-Westfalen/Germany].
AB  - BACKGROUND: It is an ongoing debate in Germany whether there is an association
      between the number of preterm infants admitted to a neonatal unit per year and
      neonatal mortality. Data from Germany on this topic are sparse and the
      generalizability of this data is questionable in face of a heterogeneous
      organization of perinatal care among federal states. METHODS: We used data from a
      state-wide quality assurance program in Nordrhein-Westfalen/Germany, encompassing
      3 930 newborns below 32 completed weeks gestation p. m. admitted during the years
      2004 and 2005. We hypothesized that there is an association between annually
      admitted premature infants below 32 completed weeks of gestation and mortality
      rates among these patients. RESULTS: Mortality below 28 completed weeks gestation
      was significantly lower in hospitals admitting more than 50 premature infants <
      32 completed weeks gestation per year compared to smaller hospitals (odds ratio
      0.55, 95 %-CI 0.41-0.74, p < 0.001). When lowering the critical threshold to
      hospitals admitting more than 40 premature infants < 32 weeks gestation, only in
      newborns < 25 completed weeks gestation a significant effect could be
      demonstrated. The level of care (level 1-3) was off less importance than patient
      volume. CONCLUSION: In Nordrhein-Westfalen/Germany, survival rate of immature
      infants is significantly higher if treated in larger neonatal intensive care
      units with a minimal annual volume of more than 40-50 premature infants < 32
      weeks GA. Patient volume seemed to be a better indicator of performance than
      formal level of care.

PMID- 17541879
TI  - [Annual patient volume and survival of very low birth weight infants (VLBWs) in
      Germany--a nationwide analysis based on administrative data].
AB  - BACKGROUND: Despite numerous international analyses addressing survival of very
      low birthweight infants (VLBWs) in relation to patient volume, only few regional
      analyses from Germany exist. Thus, the aim of this study was to perform analyses
      on a nationwide database relating to this topic. MATERIALS AND METHODS: We used
      nationwide hospital claims data according to data exchange processes designated
      in section sign 301 Social Security Code, of patients insured with the local
      healthcare insurance fund (AOK), with a hospital admission weight of 300-1 499 g,
      an age of less than 29 days, and a hospital discharge date between 1 Jan 2002 and
      30 June 2006. Mortality within 30 days of hospital admission was used as end
      point. Crude and risk adjusted analyses were performed using logistic regression.
      RESULTS: A comparison with federal statistics data showed that our dataset covers
      28 % of all VLBWs born in Germany during the study period. 9 487 VLBWs could be
      included in risk adjusted volume-outcome analyses. Significantly increased risk
      adjusted 30-day-mortality rates in smaller units were observed using different
      thresholds. The relationship was more pronounced in the most recent time period
      starting from 2004. CONCLUSION: Adoption of a minimum VLBW patient volume in
      addition to the structural requirements consented by the Federal Joint Committee
      (G-BA) seems reasonable, to maintain or improve the quality of VLBW health care
      provision in Germany.

PMID- 17541880
TI  - Anaerobic running capacity determined from a 3-parameter systems model:
      relationship with other anaerobic indices and with running performance in the 800
      m-run.
AB  - The purpose of this study was to compare anaerobic running capacity (ARC, i.e.,
      the distance that can be run using only stored energy sources in the muscle)
      determined from a 3-parameter systems model with other anaerobic indices and with
      running performance in the 800 m. Seventeen trained male subjects (.VO(2max) =
      66.54 +/- 7.29 ml . min (-1) . kg (-1)) performed an incremental test to
      exhaustion for the determination of .VO(2max) and peak treadmill velocity (PTV),
      five randomly ordered constant velocity tests at 95, 100, 105, 110, and 120 % of
      PTV to compute ARC and oxygen deficit (O(2)def, at 110 % of PTV), and a 800-m
      time trial to determine running performance (mean velocity over the distance, V
      (800 m)) and peak blood lactate concentration ([La (-)] (b, peak)). ARC (467 +/-
      123 m) was positively correlated with O(2)def (56.35 +/- 18.47 ml . kg (-1); r =
      0.57; p < 0.05), but not with [La (-)] (b, peak) (15.08 +/- 1.48 mmol . l (-1); r
      = - 0.16; p > 0.05). The O(2) equivalent of ARC (i.e., the product of ARC by the
      energy cost of running; 103.74 +/- 28.25 ml . kg (-1)), which is considered as an
      indirect estimation of O(2)def, was significantly higher than O(2)def (p < 0.01,
      effect size = 1.99). It was concluded that ARC is partially determined by
      anaerobic pathway, but that it probably does not provide an accurate measure of
      anaerobic capacity, if, however, O(2)def can be considered as a criterion measure
      for it.

PMID- 17541881
TI  - ent-Kaurane-type diterpenoids from a cell suspension culture of the liverwort
      Jungermannia subulata.
AB  - A cell suspension culture of the liverwort Jungermannia subulata was established
      from callus tissue induced by culturing spores. From the suspension culture,
      three new ent-kaurane-type diterpenoids were isolated together with three
      previously reported ent-kaurane-type diterpenoids. Five ent-kaurane-type
      diterpenoids were isolated from the intact J. subulata, two of which were new
      compounds. Their structures were determined by spectroscopic methods, chemical
      reaction, and X-ray crystallographic analysis.

PMID- 17541882
TI  - Ziprasidone outcome and tolerability: a practical clinical trial with plasma drug
      levels.
AB  - INTRODUCTION: The aim of this study was to evaluate clinical outcomes and the
      tolerability of ziprasidone in relation to its plasma levels. METHODS: Thirteen
      inpatients affected by schizophrenia were included in the study after an acute
      exacerbation phase. Ziprasidone monotherapy was administered for a period of
      eight weeks at a mean dose of 123.07+/-30.38 mg/day. Plasma concentrations were
      measured by high-performance liquid chromatography. RESULTS: Nine patients
      completed the study. A significant clinical improvement was observed, especially
      in negative symptoms ( P<0.05), and there was a significant improvement in
      extrapyramidal symptoms ( P<0.01). Clinical laboratory tests, such as ECG and
      weight, did not significantly change from baseline. Plasma ziprasidone levels
      ranged from 20 ng/mL to 160 ng/mL (mean: 75.8 ng/mL) and were significantly
      related to the improvement in negative symptoms. DISCUSSION: The study showed
      that ziprasidone was effective and tolerable, that use of ziprasidone was
      characterized by an absence of extrapyramidal symptoms and weight gain, and that
      no alterations in clinical laboratory tests occurred. The findings suggest a
      relationship between plasma levels and the clinical response to negative symptoms
      of schizophrenia.

PMID- 17541884
TI  - Atypical antipsychotics and seborrheic dermatitis: three case reports.
AB  - Seborrheic dermatitis (SD) has no diagnostic criteria and its etiology remains
      unknown. SD is distributed in the areas rich in sebaceous glands. Initially,
      MALASSEZIA FURFUR was thought to be the causing agent. Currently, SD is thought
      as not being proportional to the mean yeast count, but rather as an abnormal host
      immune response to the yeasts on the skin. There are a variety of topical and
      systemic antifungal agents available as a remedy. Corticosteroids and ultraviolet
      B are also used as treatment.

PMID- 17541883
TI  - A study of genetic (CYP2D6 and ABCB1) and environmental (drug inhibitors and
      inducers) variables that may influence plasma risperidone levels.
AB  - Risperidone (R) is metabolized to 9-hydroxyrisperidone (9-OHR) by cytochrome P450
      2D6 (CYP2D6). The main objective of this naturalistic study was to investigate
      the variables associated with two plasma ratios: the plasma R:9-OHR concentration
      ratio and the total concentration-to-dose (C:D) ratio. These ratios were studied
      as continuous measures by linear regression analyses and as three dichotomous
      variables in logistic regression analyses: R:9-OHR ratio >1 (indicative of lack
      of CYP2D6 activity), C:D ratio >14 (indicative of diminished R elimination), and
      C:D ratio <3.5 (indicative of increased R elimination). Plasma R levels;
      genotypes for CYP2D6, CYP3A5; and ABCB1 genes, and co-medication, including CYP
      inhibitors and CYP3A inducers, were studied in 277 patients. Almost all CYP2D6
      poor metabolizers (PMs) had an inverted R:9-OHR ratio (>1). Having a CYP2D6 PM
      phenotype was strongly associated with a C:D ratio >14 (OR=8.2; 95% confidence
      interval [CI]=2.0-32.7), indicating diminished R elimination. CYP2D6 ultrarapid
      metabolizers (UMs) did not exhibit an increased R elimination. Some ABCB1 (or
      MDR1) variants were significantly associated with increased R:9-OHR ratios and
      decreased C:D ratios, but the results were neither consistent nor robust. Taking
      CYP inhibitors was significantly associated with a C:D ratio >14 (OR=3.8; CI=1.7
      8.7) and with an inverted R:9-OHR ratio. Taking CYP3A inducers was significantly
      associated with a C:D ratio <3.5 (OR=41.8; CI=12.7-138), indicating increased R
      elimination. Female gender and old age appeared to be associated with a lower R
      elimination. Our study indicated that the CYP2D6 PM phenotype may have a major
      role in personalizing R doses, whereas the CYP3A5 PM phenotype probably has no
      role. CYP inducers and inhibitors appear to be relevant to R dosing. New studies
      are needed, particularly to further assess the role of the CYP2D6 UM phenotype
      and ABCB1 variants in R pharmacokinetics.

PMID- 17541885
TI  - Effects of comedication on the serum levels of aripiprazole: evidence from a
      routine therapeutic drug monitoring service.
AB  - INTRODUCTION: The objective of the study was to compare the serum concentrations
      of the atypical antipsychotic aripiprazole in monotherapy with the concentrations
      found during concomitant therapy with other drugs. METHODS: Samples analyzed for
      aripiprazole by a liquid chromatography-mass spectrometry method in a routine
      therapeutic drug monitoring setting were collected consecutively. RESULTS:
      Samples from 81 patients were included in the study. Comedication with the CYP3A4
      inducer carbamazepine lowered the dose-adjusted aripiprazole concentration by
      88%. Comedication with CYP2D6 inhibitors gave a mean concentration 44% higher
      than in the monotherapy group. Subjects comedicated with valproate had lower
      aripiprazole concentrations, while subjects comedicated with lamotrigine,
      citalopram/escitalopram and lithium had higher concentrations than the subjects
      in the monotherapy group. CONCLUSION: Although the study is small and the results
      should be interpreted very cautiously, it indicates that comedication with drugs
      inhibiting or inducing CYP2D6 or CYP3A4 affects the serum concentrations of
      aripiprazole. The other findings should be considered as preliminary and have to
      be replicated in a larger setting before firm conclusions can be drawn.

PMID- 17541886
TI  - The association between exposure to COX-2 inhibitors and schizophrenia
      deterioration. A nested case-control study.
AB  - BACKGROUND: COX-2 inhibitors (COX-2i) have been reported to have beneficial
      effects on schizophrenia. This observational study assesses the association
      between exposure to COX-2i or/and NSAIDs and schizophrenia deterioration.
      METHODS: We conducted a case-control study within a cohort (n=3,485) of
      antipsychotic users with a schizophrenia diagnosis (ICD-9=295.x) in IMS-Lifelink,
      a US claims database. Case events indicating exacerbation of schizophrenia were:
      switching antipsychotic medication, starting combination therapy, using
      parenteral antipsychotics or an increasing dose. For each case one control was
      selected. Exposure to COX-2i/NSAIDs (current/recent/none) and cumulative exposure
      in Defined Daily Doses 90 days before the index/event date were assessed. Age,
      sex and co-medication were evaluated as confounders. Logistic regression analysis
      was used to assess the association. RESULTS: 1,443 case events occurred. For
      current use, no benefit on schizophrenia case events from exposure to COX-2i was
      found (adjusted OR 1.16; 95% CI 0.83-1.62). Instead, recent COX2i use with a
      duration of 0 to 93 days was associated with an increased risk for schizophrenia
      deterioration (adjusted OR 2.56; 95% CI 1.35-4.87). This association was
      strongest in rofecoxib. No relation was found for NSAIDs. CONCLUSION: The use of
      COX-2i was not associated with a decreased risk for schizophrenia deterioration
      in this population.

PMID- 17541887
TI  - A one-day survey of characteristics of off-label hospital prescription of
      psychotropic drugs.
AB  - INTRODUCTION: The aim of this study was to explore the characteristics of off
      label prescriptions of psychotropic drugs among patients hospitalised in
      psychiatry. METHODS: A one-day cross-sectional study was used to explore off
      label prescribing in patients hospitalised in four wards of a state psychiatric
      hospital. Information regarding patients and treatment characteristics was
      collected from medical records. Off-label prescribing was defined according to
      the Summary of Product Characteristics. RESULTS: Seventy-five patients were
      included. Of the 261 prescriptions, more than one out of three (n=104, 39.8%)
      were off-label. Off-label prescribing was particularly high for anticonvulsants
      (97%), and to a lesser extent for mood stabilisers (33%) and anxiolytics (31%).
      The rate of off-label prescription was higher for 2nd compared to 1st generation
      antipsychotics. Most patients (84%) were prescribed at least one psychotropic
      drug outside of the licensed indication or recommended dosage. Patients with and
      without off-label prescription did not differ regarding history of prior
      admission, type of current admission (voluntary vs. compulsory) and diagnosis.
      CONCLUSION: In spite of its frequency in routine practice, off-label prescribing
      should not be trivialised. Prescribers should be better informed about the
      potential legal consequences of off-label prescribing.

PMID- 17541888
TI  - Value and actuality of the prescription information for therapeutic drug
      monitoring of psychopharmaceuticals: a comparison with the medico-scientific
      evidence.
AB  - Therapeutic drug monitoring (TDM) of psychopharmaceuticals, i.e., the assay of
      plasma concentrations, is a practical therapeutic application of pharmacokinetic
      principles in psychiatry. The prescription information (summary of product
      characteristics, SPC) is provided by pharmaceutical companies according to the
      requirements of regulatory authorities. The present study investigated the degree
      of agreement of German SPCs for 48 psychopharmaceuticals with the existing medico
      scientific evidence in the area of TDM. For this aim, an empirical summary score
      of SPC content related to TDM (SPCC (TDM)) was calculated and compared with the
      level of recommendation of TDM (LOR) of the AGNP-TDM expert group consensus
      guidelines. Considerable disagreement was found between the information on TDM in
      SPCs and existing medico-scientific evidence, e.g., in the case of antidepressant
      and antipsychotic drugs. Even for well studied compounds, such as amitriptyline
      and clozapine, insufficient information on TDM is included in German SPCs. Small
      differences existed in the TDM-related information in SPCs of generic drugs with,
      however, much variance between Germany, Austria and Switzerland. Generally, it
      must be concluded that deficits exist in the preparation of German SPCs for
      psychopharmaceutical drugs with respect to empirical pharmacokinetic data, i.e.,
      TDM-relevant information. It is recommended that SPCs of psychopharmaceuticals
      should be improved in terms of TDM-related information and that target plasma
      concentrations be adjusted according to the guidelines of the AGNP-TDM expert
      group. A higher level of good pharmacokinetic practice may be thus achieved.

PMID- 17541889
TI  - Isotretinoin, depression and suicide ideation in an adolescent boy.

PMID- 17541890
TI  - Successful mirtazapine treatment of an 81-year-old patient with syndrome of
      inappropriate antidiuretic hormone secretion.
AB  - Elderly patients are at a higher risk for inappropriate antidiuretic hormone
      secretion when treated with antidepressants. In response to severe depressive
      symptoms, we initiated treatment with citalopram of an 81-year-old female patient
      with slightly reduced sodium and chloride levels. The sodium and chloride levels
      decreased continuously during treatment with citalopram; six days after the
      citalopram was discontinued, sodium and chloride levels returned to normal. We
      then switched treatment to mirtazapine. Close monitoring revealed that the
      patient's sodium and chloride levels never decreased and the patient did not
      relapse for more than two months. This case study indicates that treatment with
      citalopram may worsen preexisting hyponatremia. Mirtazapine appears to be safe
      for use in high-risk, elderly patients.

PMID- 17541891
TI  - EPMS under antidepressive therapy with fluvoxamine and concomitant antibiotic
      therapy with clindamycin.

PMID- 17541893
TI  - Obsessive-compulsive disorders due to neuroacanthocytosis treated with
      citalopram.

PMID- 17541897
TI  - [Differentiation of benign paroxysmal positional vertigo subtypes].

PMID- 17541899
TI  - [Doctors' practice - hospital - doctors' clinic - day and night hospital -
      private clinic. A legal overview of medical terms].

PMID- 17541900
TI  - [Burning mouth syndrome].
AB  - Burning mouth syndrome (BMS) is characterized by oral dysesthesia, xerostomia and
      dysgeusia without visible alterations of oral mucosa. While secondary BMS results
      from an underlying general condition such as diabetes or iron deficiency, no
      causal disorder can be identified in primary BMS. The estimated prevalence is 1 -
      2%, postmenopausal women are substantially more frequently affected than men.
      Current etiologic concepts assume a focal peripheral and central neuropathy. Only
      few controlled drug trials have yet been conducted. Thioctic acid appears the
      medical treatment of choice due to its comparatively good evidence for efficacy
      and low incidence of adverse reaction. Gabapentin and pregabalin are modern GABA
      analogue anticonvulsants, which are also efficient in the treatment of peripheral
      neuropathies. Also conceptually appropriate for BMS treatment, current evidence
      for efficacy in BMS is insufficient. In two trials, local oral treatment with
      clonazepam has been beneficial in BMS. The efficacy of antidepressants is
      equivocal.

PMID- 17541901
TI  - [Structure in change--orthopedic and traumatic surgery--future structure of
      inpatient care ].

PMID- 17541902
TI  - [The basis of guidelines for growth and assessment].

PMID- 17541903
TI  - [Endoprosthesis: hip joint surface replacement--what do the patients say and what
      are the revision rates?].

PMID- 17541904
TI  - [Application experience with the modular valuation system (PUV) and critical
      comments].

PMID- 17541905
TI  - [Commentary to the diagnostic and therapeutic recommendations of Polish Lung
      Cancer Group (see page 88)].

PMID- 17541906
TI  - [COPD - diagnosed too rarely, not only at an early-stage (see page 40)].

PMID- 17541907
TI  - [Transbronchial needle aspiration as a diagnostic method in lung cancer and non
      malignant mediastinal adenopathy].
AB  - INTRODUCTION: The aim of the study was to assess the diagnostic yield of
      transbronchial needle aspiration (TBNA) in mediastinal or hilar adenopathy in:
      lung cancer, staging of NSCLC, sarcoidosis and other non-malignant diseases.
      MATERIAL AND METHODS: Transbronchial needle aspiration was performed in 347
      consecutive patients - 402 biopsies in groups of lymph nodes: subcarinal (7) -
      179, all paratracheal (2R, 2L, 4R, 4L) - 168 and hilar (10R, 10L) - 55, with no
      real-time imaging guidance, preceded by computed tomography (CT), using 22-gauge
      needles. All negative results in NSCLC patients were verified by transcervical
      extended bilateral mediastinal lymphadenectomy (TEMLA) and the remaining patients
      underwent mediastinoscopy or thoracotomy. RESULTS: TBNA technique was diagnostic
      in 67.1% of lung cancer patients and in 59.0% of patients with sarcoidosis. In
      the group of all lung cancer patients specificity was 100%, sensitivity 88.5%,
      accuracy 91.8% and negative predictive value 77.9% and in diagnosing of lymph
      nodes involvement in NSCLC was respectively 100%, 86.6%, 90.7% and 76.6%. The
      high diagnostic yield was comparable for all mediastinal groups. In 80% of NSCLC
      patients with false negative results of TBNA there was observed partial
      involvement of metastatic lymph nodes, confirmed by TEMLA. CONCLUSIONS: The
      diagnostic value of TBNA is very high in diagnostics of lung cancer, NSCLC
      staging and sarcoidosis but much lower in lymphomas, tuberculosis and other non
      malignant diseases.

PMID- 17541908
TI  - [Analysis of occurrence of DRB and DQ alleles in sarcoidosis and tuberculosis
      from Northern Poland].
AB  - INTRODUCTION: Sarcoidosis is a multisystem disorder of unknown etiolgy.
      Pathologic similarities between SA and tuberculosis (TB) suggest M. tuberculosis
      antigen(s) as causative agents. It seems likely that in the genetically different
      predisposed hosts, the same antigen(s) may cause the development of sarcoid or
      tuberculous immune response. AIM: The aim of this study was to compare the
      frequency of occurrence of HLA class II alleles in SA, TB and in the healthy
      individuals. MATERIAL AND METHODS: To test a difference in haplotypes associated
      with both diseases, we compared the distribution of DQA1 and DQB1 alleles in 45
      SA patients, 62 TB patients and in 143 healthy volunteers, using a PCR-SSP "low
      (DRB1, DQB1) and high (DQA1) resolution" method. RESULTS: Our results revealed
      that DRB1*03, DRB1*11, DQB1*02 i DQA1*0501 in Stage I of SA with Lofgrens syndrom
      (Ls) and DRB1*15, DQA1*0102, DQA1*0103 in Stage II of SA were more common,
      whereas DRB1*16, DRB1*04, DRB1*08, DQB1*02, DQB1*03, DQB1*05, DQA1*0102,
      DQA1*0301 in Ls and DQB1*02, DQB1*03, DQB1*05, DQA1*0102, DQA1*0301 in Stage II
      were less common than in the controls but after Bonferroni correction occurrence
      of DRB1*04, DQB1*02, DQB1*03, DQB1*05 and DQA1*0102, DQA1*0301, DQA1*0501 was
      significantly differ. In TB group, DRB1*16, DRB1*14, DQB1*05 i DQA1*0303 were
      more frequent and DRB1*11, DQB1*02, DQA1*0201, DQA1*0505 less frequently present
      as compared to the controls, but after correction DRB1*16, DQB1*02, DQB1*05,
      DQA1*0303, DQA1*0505 were significantly different. In SA, DRB1*11, DQB1*02 i
      DQA1*0201, DQA1*0501, DQA1*0505 in Ls and DRB1*15, DRB1*11, DQA1*0102 in Stage II
      were more common and DRB1*16, DRB1*04, DRB1*14, DQB1*03, DQB1*05, DQB1*06,
      DQA1*0301, DQA1*0302, DQA1*0303 in Ls and Stage II were less frequent than in the
      TB group. DQB1*02, DQA1*0501 (Ls) and DRB1*15 (Stage II) were more frequently
      present in SA than in TB, even after Bonferroni correction. CONCLUSIONS: In
      summary, we identified associations of HLA class II alleles in SA and TB with
      expression pattern specific and different for each group. In most cases, in SA
      patients frequency of HLA class II alleles occurrence is opposite to the
      frequency in TB patients.

PMID- 17541909
TI  - [The significance of spoligotyping method in epidemiological investigations of
      tuberculosis].
AB  - INTRODUCTION: The control of tuberculosis (TB) requires methods for rapid
      detection and tracing sources of infection, so that further transmission can be
      arrested. Recent developments in molecular biology have resulted in techniques
      that allow prompt identification and tracking specific strains of M. tuberculosis
      as they spread through the population. Most of these techniques take advantage of
      M. tuberculosis DNA polymorphism and are based on various repetitive DNA elements
      as genetic markers. Each method yields strain-specific genetic profiles
      (fingerprints). Strains showing identical fingerprints are referred to as
      clustered and are usually associated with recent transmission, whereas strains
      whose fingerprints are unique are presumed to represent remote transmission, a
      reactivation of infection acquired in the distant past. MATERIAL AND METHODS: In
      recent years, spoligotyping has become one of the most widely used genotyping
      method for epidemiological studies of TB. Spoligotyping is a PCR-based method
      allowing to analyze strain-dependent polymorphisms observed in spacer sequences
      present within the direct repeat (DR) genomic region of M. tuberculosis complex
      strains. Spoligotyping provides some important advantages over other genotyping
      techniques. These are simplicity, rapidity, high reproducibility and stability of
      the results, with the latter being expressed in a simple digital pattern, readily
      named and databased, and the ability to perform spoligotyping directly on
      clinical samples, without the need for prior culture. However, spoligotyping has
      relatively low discriminatory capacity, which makes it necessary to use secondary
      fingerprinting methods to prove clonality between isolates. RESULTS: The aim of
      this study was to evaluate the usefulness of spoligotyping in epidemiological
      investigations of TB by analyzing 16 isoniazid-resistant M. tuberculosis strains
      isolated from patients with pulmonary TB in the central region of Poland. A total
      of 11 distinct spoligopatterns were obtained. 9 isolates were represented by a
      unique pattern, whereas 7 were clustered in 2 groups of 5 and 2 isolates,
      respectively. When compared with an international spoligodatabase SpolDB4, 13
      isolates shared already described spoligotypes, whereas 3 did not match any
      existing spoligopattern in database and were defined as orphans. Spoligotyping
      overestimated the number of clustered isolates in one of its two clusters when
      compared to IS6110 Mtb1/ /Mtb2 PCR. Strains clustered using the latter method
      were assumed to be closely epidemiologically related. CONCLUSION: This report
      demonstrates the utility of spoligotyping as an initial screening technique, to
      be supplemented by another typing method of greater discriminatory power, such as
      the IS6110 Mtb1/Mtb2 PCR in order to better recognize the epidemiological links
      between TB patients.

PMID- 17541910
TI  - [Tuberculosis caused by XDR resistant Mycobacterium tuberculosis in Poland.
      Microbiological and molecular analysis].
AB  - INTRODUCTION: The retrospective analysis of frequency of drug resistant
      tuberculosis XDR (XDR = MDR + resistance to: fluoroquinolones + amikacin and/or
      capreomycin) in Poland have been tested. MATERIAL AND METHODS: Pattern of
      resistance to first, second and third line drugs has been tested among new and
      treated patients. The total number of 10 913 Mycobacterium tuberculosis strains
      isolated from the same number of the patients surveyed in 1997-2004 in WHO
      programme Drug resistance surveillance countrywide study. RESULTS: One HIV
      negative patient (43 years old men) was infected by XDR (0,4% among new and
      treated MDR cases). Molecular analysis of the XDR strain by spoligotyping has
      been shown the T11558 cluster. Three others tuberculosis patients living in the
      same region of Poland excreted the Mycobacterium tuberculosis strains belonged to
      the same T11558 cluster, but they had not pattern of XDR resistance. In the same
      T11558 molecular cluster 13/15 - 87% strains have been isolated from polish
      patients. CONCLUSIONS: In Poland Mycobacterium tuberculosis resistance to
      fluoroquinolones, capreomycin and amikacine among MDR strains has been observed
      very rarely.

PMID- 17541911
TI  - [Analysis of deaths caused by obstructive pulmonary diseases in Pomerania
      province in 2001-2004].
AB  - INTRODUCTION: Lung diseases, especially COPD, are one of the leading causes of
      death. The aim of the study was to assess mortality caused by COPD, asthma and
      cor pulmonale in the years 2001-2004 in the Pomerania province. MATERIAL AND
      METHODS: Death certificates of patients who died of asthma, COPD or cor pulmonale
      registered in Regional Health Centre were analyzed. RESULTS: The mortality rate
      for COPD was 14.02/100 000, asthma 2.04/100 000 and cor pulmonale 2.4/100 000
      inhabitants. Mortality rate from COPD increased from 12.5/100 000 found in 2001
      to 15.6/100 000 found in 2004 (p = 0.005). The number of deaths was higher in the
      winter time. The peak mortality was found in patients 65 years old. 71% of COPD
      and cor pulmonale patients died in the hospital, whereas 75% of asthma deaths
      occurred at home (p = 0.0001). CONCLUSIONS: The mortality rates from chronic
      respiratory diseases in the analyzed population are comparable to data found in
      other studies. The alarming result is the increase in the number of COPD deaths
      and high percentage of asthma patients who die at home.

PMID- 17541912
TI  - [Influence of treatment with continuous positive airway pressure on respiratory
      muscle function and physical fitness in patients with obstructive sleep apnoea
      and overlap syndrome].
AB  - INTRODUCTION: The aim of this study was to evaluate the effect of CPAP treatment
      on respiratory muscle strength and exercise tolerance in patients with
      obstructive sleep apnoea (OSA) and overlap syndrome (OS). MATERIAL AND METHODS: 9
      patients with OSA and 9 patients with OS were studied. Respiratory muscle
      assessment, 6 minute walking distance (6MWD) and cycloergometry exercise test
      were performed before and after six month period of CPAP treatment. RESULTS: In
      OSA group exercise tolerance did not change after the treatment. Mean 6MWD was
      571.8 +/- 76.6 m before and 554.0 +/- 125.5 m after treatment, mean W(max) was
      142 +/- 41 W before and 139 +/- 38 W after treatment. PI(max) in OSA group did
      not change significantly, 140.4 +/- 32.0 cm H(2)O before and 155.9 +/- 31.5 after
      treatment (p = 0.14). PE(max) improved from 170.5 +/- 49.2 cm H(2)O, to 199.9 +/-
      27.6 cm H(2)O (p = 0.067). Handgrip force in OSA group improved from 50.5 +/-
      16.5 kg to 61.0 +/- 17.0 kg (left hand) (p = 0.05) and from 53.3 +/- 14.2 to 58.9
      +/- 15.9 (right hand) (p < 0.05). In OS group exercise tolerance improved by 17%
      after CPAP treatment from W(max) = 81 +/- 33 W before to 95 +/- 38 W after. Mean
      6MWD was at the same level before (504 +/- 144 m) and after treatment (492 +/-
      108 m). PI(max) in OS group improved from 89.2 +/- 35.7 cm H(2)O to 106.3 +/-
      31.4 cm H(2)O (p < 0.05). PE(max) in OS group did not change significantly, 159.9
      +/- 45.8 cm H(2)O before and 184.2 +/- 45.0 cm H(2)O after treatment (NS).
      Handgrip force in OS group improved from 38.1 +/- 15.9 kg to 46.9 +/- 11.1 kg
      (left hand) (p < 0.05) and did not change in right hand (44.5 +/- 17.7 kg vs.
      47.9 +/- 10.4 kg) (NS). Data analysis of the whole group (18 pts) showed clear
      tendency to improve strength of respiratory muscles in patients treated with
      CPAP. Mean PI(max) improved from 123 to 133 cm H(2)O (p = 0.006) and PE(max)
      improved from 168.1 to 192 cm H(2)O (p = 0.02). CONCLUSIONS: CPAP treatment
      improved strentgh of respiratory and skeletal muscles in patients with OSA and OS
      and improved exercise tolerance in patients with OS.

PMID- 17541913
TI  - [A comparative evaluation of immunohistochemical markers for the differential
      diagnosis between malignant mesothelioma, non-small cell carcinoma involving the
      pleura, and benign reactive mesothelial cell proliferation].
AB  - INTRODUCTION: Histopathological diagnosis of malignant mesothelioma (MM) and
      differentiating it from tumors infiltrating the pleura is very difficult.
      Distinguishing benign reactive mesothelial cell proliferation from MM also
      presents problems. The objective of this study was to evaluate the significance
      of selected immunohistochemical stains in differentiating MM from non-small cell
      lung cancers infiltrating the pleura and from benign reactive mesothelial cell
      proliferation. MATERIAL AND METHODS: The material encompassed 86 cases of MM, 54
      cases of NSCLC infiltrating the pleura, and 43 cases of benign reactive
      mesothelial cell proliferation. The MM cases were reclassified according to the
      WHO criteria (2004): epithelioid, 61 cases (71%), including well-differentiated
      papillomatous, 3 cases; sarcomatous, 6 cases (6.8%); fibrous, 4 cases (4.7%);
      biphasic, 15 cases (17.5%). A panel of immunohistochemical stains was used in
      this study. It included broad-spectrum antibodies to cytokeratins (CKAE1/AE3,
      CKMNF116), vimentin, epithelial membrane antigen (EMA), mesothelial cells (HBME1,
      CK5/6, calretinin), adenocarcinoma cells (BerEp4, B72.3, CEA, TTF1), antibodies
      enabling the assessment of proliferation (Mib1) and cell-cycle regulating
      proteins (p53). RESULTS: Coexpression of cytokeratins and vimentin was found in
      63.9% of MM cases and cell-membrane reactions with EMA were seen in 58.9%.
      Positive staining for HBME1, CK5/6, calretinin, BerEp4, B72.3, CEA and p53 was
      obtained in 76.7%, 51.2%, 66.7%, 1.2%, 6.2%, 1.2% and 51% of the cases,
      respectively. None of the MM cases stained for TTF1. MM by WHO subgroups:
      Coexpression of cytokeratins and vimentin occurred in 55.7% cases of epithelioid
      MM, 93.3% of biphasic MM, 66.6% of sarcomatous MM, and in 100% of fibrous MM
      cases. Positive staining for HBME1, CK5/6, and calretinin was seen only in the
      epithelioid and mixed subtypes of MM; the respective percentages of positive
      reactions were: HBME1, 90.2% and 73.3%; CK5/6 58.2% and 53.3%; calretinin, 72%
      and 75%. Non-small cell lung cancers infiltrating the pleura: Coexpression of
      cytokeratin and vimentin was found in 17.6% of the cases, positive staining of
      membranes for EMA, in 13% cases. Positive staining for HBME1 was observed in
      22.6% of the cases, for CK5/6, in 9.3%, for calretinin, in 2%, for BerEp4, in
      72.2%, for B72.3, in 64.1%, for CEA, in 58.5%, and for TTF1, in 43.8%. Benign
      reactive mesothelial cell proliferation: Protein p53 was present in 9.3% of
      cases, whereas no positive staining for EMA was found. Differentiation of MM from
      non-small cell carcinomas: Among the antibodies used in the study, anti-HBME1 had
      the highest sensitivity (76.7%) but lowest specificity (77.4%). Staining for
      calretinin showed high specificity (99.8%), as did CEA and TTF1 (98.8% and 100%),
      with moderate sensitivity (66.7%, 58.5% and 43.8%, respectively). BerEp4 showed
      the highest sensitivity (72.2%) and specificity (98.8%). CONCLUSION: In
      diagnosing mesothelioma it is necessary to use a panel of immunohistochemical
      stains, which should contain antibodies to markers for adenocarcinoma and
      mesothelioma. Due to the high costs of such a study, a two-stage method is
      advantageous. The best combination of sensitivity and specificity was found for
      BerEp4, CEA, and TTF1 and for calretinin and HBME1. In the diagnosis of spindle
      cell pleural tumors and the fibrous form of MM and benign reactive mesothelial
      cell proliferation , markers of mesothelial cells are noncontributory.
      Immunohistochemical staining fails to identify a reactive process, but a diffuse,
      positive stain for EMA and the presence of protein p53 support the diagnosis of
      MM.

PMID- 17541914
TI  - [Quality of life of patients with asthma which has been well and poorly
      controlled].
AB  - INTRODUCTION: The aim of the study was to assess the quality of life of patients
      with asthma who were well and poorly controlled. MATERIAL AND METHODS: 70
      patients with diagnosed asthma, aged from 18 to 40, were included into the study
      between November 2005 and February 2006 at the Specialist Hospital in Chojnice
      and Allergy out-patient Clinic of Medical University of Gdansk. The diagnosis and
      stage of asthma, as well as the assessment of the control of disease was
      performed by the physician. Quality of life was assessed with the use of St.
      George Respiratory Questionnaire (SGRQ). Statistical analysis was made with the
      use of computer statistical program Statistica. RESULTS: According to GINA in 26
      patients mild asthma was diagnosed, in 31 - moderated and in 13 - severe disease.
      41 patients were assessed as well controlled and 29 - as poorly controlled. Older
      age and longer duration of the disease were related to severe asthma, p = 0.01
      and p = 0.003, respectively. In well controlled patients overall score for SGRQ
      was 48.86, whereas in poorly controlled was - 74.4. There was a significant
      difference between the overall quality of life in well and poorly controlled
      patients with asthma, p = 0.0001. This difference was found in all three domains:
      for symptoms, activity and impact on life, p = 0.014, p = 0.035 and p = 0.003,
      respectively. CONCLUSIONS: Quality of life is strongly dependent on the control
      of symptoms in asthmatic patients.

PMID- 17541915
TI  - [The epidemiology of lung cancer].
AB  - Lung cancer is currently most frequently diagnosed neoplasm in males and the
      fifth most frequent cancer in females. In developed countries only breast cancer
      is diagnosed more often in women. Worldwide, lung cancer is the most common cause
      of cancer mortality in males and females. In the Europe lung cancer accounts for
      21% of all cancer cases in males and 29% of all cancer deaths. The rapid increase
      in lung cancer incidence was observed the since beginning of the XX century till
      1990-1994. The incidence in males decreased recently, but still increases in
      females, especially in young women. The changes in frequency of various
      histological subtypes of lung cancer are observed too. Despite many clinical
      trials, modern diagnostic techniques and improved supportive care, the prognosis
      remains unfavourable and long-term survival almost did not change. In Poland the
      incidence of lung cancer in 2002 was 81.9/100 000 in males and 22.2/100 000 in
      females. In both genders 1-year and 5-year survivals time are one of the shortest
      in Europe.

PMID- 17541916
TI  - [Optoelectronic plethysmography -- a new technic to measure changes of chest wall
      volume].
AB  - Optoelectronic plethysmography (OEP) is a new, noninvasive diagnostic tool that
      allows to measure changes of chest wall volume and its three compartments.
      Mathematical basis of the method, elements of the system and possibilities of
      combining OEP with other recording techniques used in pneumonology were discussed
      in details. OEP applications, results of the latest investigations and
      development perspectives were briefly presented.

PMID- 17541917
TI  - [Small-cell lung cancer diagnostic and therapeutic recommendations of Polish Lung
      Cancer Group].
AB  - Small-cell lung cancer is characterized by an aggressive clinical course with
      high tendency for early dissemination. At presentation, patients are usually
      symptomatic and with hilar or mediastinal mass at radiography. Staging should be
      focused on identifying any evidence of distant spread. Chemotherapy including
      cisplatin and etoposide is a cornerstone of treatment for all patients. Limited
      stage disease should be managed by chemotherapy combined with concurrent chest
      irradiation. All patients who achieve complete response should be considered for
      elective cranial irradiation. Surgical treatment may be used in highly selected
      patients with TNM stage I disease, and surgery should always be combined with
      chemotherapy. Extensive-stage disease should be managed by multi-agent
      chemotherapy alone. Long-term survivors should undergo careful monitoring for
      development of a second primary tumour.

PMID- 17541918
TI  - [Unusual cause of right heart failure decompensation in 21-years old patient with
      idiopathic pulmonary arterial hypertension -- a case report].
AB  - The authors describe a case of 21-years old woman with idiopathic pulmonary
      arterial hypertension with atypical clinical consequences of massive internal
      bleeding. Despite significant hypovolemia clinical and laboratory presentation
      was one of RV failure with dilatation of right heart ventricle and increased
      plasma level of markers of myocardial stretch and injury (NT-proBNP and troponin,
      respectively). This is attributed to impaired right ventricular coronary
      perfusion and hypoxia. Intensive treatment restored baseline RV conditions and at
      15 months follow-up no persistent right heart impairment was observed. This case
      demonstrates that bleeding should be also considered in differential diagnosis of
      exacerbation of right ventricular failure in patients with pulmonary arterial
      hypertension.

PMID- 17541919
TI  - [Cardiac sarcoidosis -- own experiences].
AB  - Cardiac involvement in sarcoidosis may be incidentally discovered without any
      symptoms of the disease. When undiagnosed and untreated it is potentially fatal.
      Although there is no recommended strategy for the diagnosis, the introduction of
      newer technology is promising and may be useful for early diagnosis of sarcoid
      heart disease and for the evaluation of response to therapy. We present a case of
      53-years old woman, with asymptomatic cardiac arrhythmias and x-ray chest picture
      changes without any respiratory symptoms. Further assessment and the use of
      cardiac magnetic resonance imaging allowed a diagnosis of cardiac sarcoidosis to
      be made.

PMID- 17541921
TI  - [First Polish-French Pneumonological Conference, Poznan, 2nd December 2006].

PMID- 17541922
TI  - PLA nano- and microparticles for drug delivery: an overview of the methods of
      preparation.
AB  - The controlled release of medicaments remains the most convenient way of drug
      delivery. Therefore, a wide variety of reports can be found in the open
      literature dealing with drug delivery systems. In particular, the use of nano-
      and microparticles devices has received special attention during the past two
      decades. PLA and its copolymers with GA and/or PEG appear as the preferred
      substrates to fabricate these devices. The methods of fabrication of these
      particles will be reviewed in this article, describing in detail the experimental
      variables associated with each one with regard to the influence of them on the
      performance of the particles as drug carriers. An analysis of the relationship
      between the method of preparation and the kind of drug to encapsulate is also
      included. Furthermore, certain issues involved in the addition of other monomeric
      substrates than lactic acid to the particles formulation as well as novel
      devices, other than nano- and microparticles, will be discussed in the present
      work considering the published literature available.

PMID- 17541923
TI  - In situ micro-sized gel-forming injectable implant using biodegradable
      amphiphilic graft copolymer.
AB  - A synthesized graft polymer is used as a biodegradable polymer for an in situ gel
      forming injectable implant system. The amphiphilic character of the polymer in
      the graft structure lowered the viscosity of the polymer solution, which enabled
      easy injection. A micro-sized gel can be obtained with this system, which has not
      been found for previous in situ gel-forming systems with poly[(D,L-lactide)-co
      glycolide] copolymer. In addition, a protein particle embedded gel exhibits good
      in vitro drug release performance as a result of the enhanced stability and
      shorter diffusion length.

PMID- 17541924
TI  - Direct transfer of preformed patterned bio-nanocomposite films on polyelectrolyte
      multilayer templates.
AB  - Microarrays containing multiple, nanostructured layers of biological materials
      would enable high-throughput screening of drug candidates, investigation of
      protein-mediated cell adhesion, and fabrication of novel biosensors. In this
      paper, we have examined in detail an approach that allows high-quality
      microarrays of layered, bionanocomposite films to be deposited on virtually any
      substrate. The approach uses LBL self-assembly to pre-establish a multilayered
      structure on an elastomeric stamp, and then uses microCP to transfer the 3-D
      structure intact to the target surface. For examples, different 3-D patterns
      containing dendrimers, polyelectrolyte multilayers and two proteins, sADH and
      sDH, have been fabricated. For the first time, the approach was also extended to
      create overlaid bionanocomposite patterns and multiple proteins containing
      patterns. The approach overcomes a problem encountered when using microCP to
      establish a pattern on the target surface and then building sequential layers on
      the pattern via LBL self-assembly. Amphiphilic molecules such as proteins and
      dendrimers tend to adsorb both to the patterned features as well as the
      underlying substrate, resulting in low-quality patterns. By circumventing this
      problem, this research significantly extends the range of surfaces and layering
      constituents that can be used to fabricate 3-D, patterned, bionanocomposite
      structures. [image in text]

PMID- 17541925
TI  - Lipase-catalyzed synthesis and curing of high-molecular-weight polyricinoleate.
AB  - High-molecular-weight polyricinoleate, with an M(w) of 100,600, was enzymatically
      prepared by the polycondensation of methylricinoleate using immobilized lipase
      from Pseudomonas cepacia (IM-PC) in bulk in the presence of 4 A molecular sieves
      at 80 degrees C for 7 d. Polyricinoleate was a viscous liquid at room temperature
      with a glass transition temperature (T(g)) of -74.8 degrees C, showed no
      crystallinity and was biodegraded by activated sludge. Polyricinoleate was
      readily cured using a dicumyl peroxide at 170 degrees C for 30 min to produce a
      chloroform insoluble crosslinked polyricinoleate with a hardness of 50A using
      durometer A.

PMID- 17541926
TI  - Hydrogels prepared from unsubstituted cellulose in NaOH/urea aqueous solution.
AB  - Novel cellulose hydrogels were synthesized through a "one-step" method from
      cellulose, which was dissolved directly in NaOH/urea aqueous solution, by using
      epichlorohydrin as crosslinker. Structure and properties of the hydrogels were
      characterized by using SEM, NMR, and water absorption testing. The hydrogels are
      fully transparent and display macroporous inner structure. The equilibrium
      swelling ratios of the hydrogels in distilled water at 25 degrees C are in the
      range from 30 to 60 g H(2)O/g dry hydrogel. Moreover, the reswelling water uptake
      of the hydrogels could be achieved to more than 70% compared with their initial
      swelling states. This work provided a simple and fast method for preparing eco
      friendly hydrogels from unsubstituted cellulose.

PMID- 17541927
TI  - Mechanical properties of comonomer-compositionally fractionated poly[(3
      hydroxybutyrate)-co-(3-mercaptopropionate)] with low 3-mercaptopropionate unit
      content.
AB  - The mechanical properties, such as Young's modulus, yield strength, and the
      elongation at breakage, were investigated for several sulfur-containing
      biopolymers P(3HB-co-3MP). A series of P(3HB-co-3MP) samples with 3MP unit
      content ranging from 6.6 to 39.1 mol-% was biosynthesized by fermentation using
      the PHA-synthesizing bacteria Cupriavidus necator. For comparison, the
      bacterially synthesized P(3HB) and P(3HB-co-3HP) with the 3HP unit content
      ranging from 13.1 to 21.1 mol-% were also investigated. It was found that the
      sulfur-containing P(3HB-co-3MP) is much more durable to stretching. Notably,
      P(3HB-co-3MP) with the 3MP unit content of only 6.6 mol-% was found to show
      excellent mechanical properties.

PMID- 17541928
TI  - Melt spinning of bacterial aliphatic polyester using reactive extrusion for
      improvement of crystallization.
AB  - This paper reports on an attempt to use reactive extrusion with peroxide as a
      comfortable pathway for improvement of the crystallization of poly(3
      hydroxybutyrate) in a melt spinning process. At first, rheological and thermal
      properties of the modified melts are determined in order to assess the effect of
      nucleation. Then spinning tests are carried out. Molecular weights and molecular
      weight distributions of the spun fibers are determined by chromatographic
      methods. Average crystallite size is measured by wide angle X-ray scattering.
      Thermal and textile properties of the spun PHB fibers are also determined. An
      estimation of the improvement of the crystallization in the spinline and of the
      inhibition of the secondary crystallization in the fibers from the use of the
      described way of reactive extrusion is given.

PMID- 17541929
TI  - Enhanced stereocomplex formation of poly(L-lactic acid) and poly(D-lactic acid)
      in the presence of stereoblock poly(lactic acid).
AB  - Stereoblock poly(lactic acid) (sb-PLA) is incorporated into a 1:1 polymer blend
      system of poly(L-lactic acid) (PLLA) and poly(D-lactic acid) (PDLA) that has a
      high molecular weight to study its addition effect on the stereocomplex (sc)
      formation of PLLA and PDLA. The ternary polymer blend films are first prepared by
      casting polymer solutions of sb-PLA, PLLA, and PDLA with different compositions.
      Upon increasing the content of sb-PLA in the blend films the sc crystallization
      is driven to a higher degree, while the formation of homo-chiral (hc) crystals is
      decreased. Lowering the molecular weight of the incorporated sb-PLA effectively
      increases the sc formation. Consequently, it is revealed that sb-PLA can work as
      a compatibilizer to improve the poor sc formation in the polymer blend of PLLA
      and PDLA.

PMID- 17541930
TI  - Fluoropolymer based on a polyaspartamide containing 1,2,4-oxadiazole units: a
      potential artificial oxygen (O2) carrier.
AB  - In this preliminary work we have prepared a fluorinated polymer capable of
      solubilizing an appreciable amount of O(2) and, at the same time, maintaining a
      higher water solubility than perfluoroalkanes investigated as injectable O(2)
      carriers. In particular, we describe the synthesis and characterization of a new
      macromolecular conjugate obtained by derivatization of alpha,beta-poly(N-2
      hydroxyethyl)-DL-aspartamide (PHEA) with 5-pentafluorophenyl-3-perfluoroheptyl
      1,2,4-oxadiazole, called PHEA-F. This new water soluble fluoropolymer was
      prepared in high yield using a simple procedure. It was characterized by FT-IR
      and UV-vis spectrophotometry, (19)F-NMR and SEC measurements. O(2) solubility
      studies on PHEA-F aqueous solutions were carried out at 25 degrees C and 37
      degrees C at atmospheric pressure and showed that PHEA-F conjugate, despite its
      low degree of derivatization in fluorine containing groups (2.60 mol-%), is
      capable of dissolving 13-15% more O(2) than non-fluorinated PHEA. Moreover, O(2)
      release in simulated physiological conditions is faster for PHEA-F than for PHEA.
      The biocompatibility of this conjugate has been evaluated by performing an in
      vitro viability assay on human chronic myelogenous leukaemia cells (K-562) chosen
      as a model cell line and in vitro haemolysis experiments on human RBCs. All these
      properties suggest the potential use of PHEA-F as an artificial O(2) carrier.

PMID- 17541931
TI  - Variation in copolymer composition and molecular weight of polyhydroxyalkanoate
      generated by saturation mutagenesis of Aeromonas caviae PHA synthase.
AB  - Amino acid substitutions at two residues downstream from the active-site
      histidine of polyhydroxyalkanoate (PHA) synthases are effective for changing the
      composition and the molecular weight of PHA. In this study, saturation
      mutagenesis at the position Ala505 was applied to PHA synthase (PhaCAc) from
      Aeromonas caviae to investigate the effects on the composition and the molecular
      weight of PHA synthesized in Ralstonia eutropha. The copolymer composition and
      molecular weight of PHA were varied by association with amino acid substitutions.
      There was a strong relationship between copolymer composition and PHA synthase
      activity of the cells. This finding will serve as a rationale for producing
      tailor-made PHAs.

PMID- 17541932
TI  - Resveratrol and trimethylated resveratrol protect from acute liver damage induced
      by CCl4 in the rat.
AB  - The importance of hydroxyl groups in the antioxidant and hepatoprotective
      properties of resveratrol was investigated. To achieve this, resveratrol or its
      trimethylated analog were administered (10 mg kg(-1), p.o.) to male Wistar rats
      and liver damage was induced by acute administration of CCl4 (4 g kg(-1), p.o.);
      appropriate controls were performed. The animals were killed 24 h after CCl4
      intoxication. The amount of reduced glutathione (GSH) in the liver was not
      modified by any treatment; interestingly, the GSH/GSSG (oxidized glutathione)
      ratio decreased in the groups receiving CCl4 and resveratrol associated with an
      increase in GSSG. In blood GSH and the GSH/GSSG ratio were decreased by CCl4;
      both effects were completely prevented by any of the compounds tested. Lipid
      peroxidation and the activity of gamma-glutamyl transpeptidase were increased
      significantly after CCl4. Resveratrol partially prevented these increases and
      surprisingly, trimethylated resveratrol completely prevented the increase of
      these markers. Both compounds partially but significantly prevented the increase
      in the activity of alanine aminotransferase; this result agrees with observations
      in the histological analysis. Both tested compounds administered alone produced
      no effect. The results of the present study suggest that OH groups are important
      for the antioxidant and hepatoprotective properties of the molecule of
      resveratrol; nevertheless, these effects can be improved by replacing hydrogen by
      a methyl in these groups. The differences in the antioxidant and hepatoprotective
      effects of these compounds could be due to the possibility that the trimethylated
      resveratrol acts like a prodrug, prolonging, probably, the half-life of the
      original compound.

PMID- 17541933
TI  - Review of the 6th national meeting of the Italian Society of Virology, a joint
      meeting with Virus Group of the Society for General Microbiology (UK).

PMID- 17541934
TI  - Intranuclear mobility of estrogen receptor alpha and progesterone receptors in
      association with nuclear matrix dynamics.
AB  - We analyzed the intranuclear dynamics of estrogen receptor alpha (ER alpha) and
      progesterone receptor (PR)-A/B labeled with different spectral variants of green
      fluorescent protein (GFP) in living cells. The distribution of ER alpha and PR
      A/B were changed from a diffuse to discrete pattern after the addition of both
      ligands, but the extent of discrete cluster formation of PR-A/B was lower than
      that of ER alpha. The nuclear areas where PR-A/B were accumulated were
      colocalized with the cluster of ER alpha, suggesting that cross-talk in the
      transcriptional regulation occurred in the loci. Fluorescence recovery after
      photobleaching (FRAP) analysis revealed that the mobility of PR-A/B was hastened
      by the coexistence of ER alpha, while the mobility of ER alpha was not changed by
      the coexistence of PR-A/B. Cluster formation was correlated with the nuclear
      matrix binding, because nuclear matrix binding capacity was also lower in PR-A/B
      than ER alpha. By ATP-depletion from the cells, most of ER alpha and PR-A/B were
      bound to the nuclear matrix and their mobilities were extinguished both in the
      absence and presence of ligand. Fluorescent protein (FP) tagged nuclear matrix
      component protein (NuMA), which was colocalized with ER alpha and PR-A/B, showed
      ATP-dependent rapid exchange in the nucleus. These results indicate that the
      mobility of ER alpha and PR-A/B is associated with the dynamics of the nuclear
      matrix.

PMID- 17541935
TI  - Glucocorticoid induced expression of connective tissue growth factor contributes
      to lactogenic differentiation of mouse mammary epithelial cells.
AB  - The response of mammary epithelial cells to basement membrane and stroma induced
      signals contributes to the degree of differentiation in this tissue. The studies
      reported here indicate that connective tissue growth factor (CTGF) is highly
      elevated during lactogenic differentiation of the HC11 mouse mammary epithelial
      cell line. In addition, CTGF is expressed in the mouse mammary gland during
      pregnancy and lactation and it is expressed in primary mammary epithelial cell
      cultures established from pregnant mice. In HC11 cells CTGF is transcriptionally
      regulated by dexamethasone, but not by estrogen or progesterone, and CTGF
      expression is not dependent on TGFbeta. CTGF contributes to and is required for
      lactogenic differentiation of HC11 cells, as demonstrated by increased
      differentiation following expression of plasmid-encoded CTGF and decreased
      differentiation following depletion of endogenous CTGF with siRNA. Moreover, HC11
      mouse mammary epithelial cells infected with an adenoviral vector encoding CTGF
      exhibit increased lactogenic differentiation. Plasmid vector-induced elevation of
      CTGF levels also increased the level of beta1 integrin in HC11 cells. Because the
      production of stromal factors is an important component of differentiation in
      mammary epithelial cells, the regulation of CTGF by glucocorticoids may play a
      critical role in this aspect of the control of differentiation. The studies
      reported here provide important information on the role of CTGF in mammary
      epithelial cell differentiation.

PMID- 17541936
TI  - Primary angiosarcomas of the breast.
AB  - BACKGROUND: The purpose of the study was to describe the clinicopathologic
      characteristics and clinical outcomes of patients with primary breast
      angiosarcoma. METHODS: The institutional database was searched to identify breast
      angiosarcoma patients seen between 1965 and 2002. Survival outcomes were
      estimated by the Kaplan-Meier method. The log-rank test was used to compare
      groups. Cox proportional hazards models were used for multivariate analysis.
      RESULTS: In all, 69 patients were identified. Median follow-up was 40 months
      (range, 0-413 months). Median age was 46. Median tumor size at diagnosis was 5.5
      cm. Thirteen (18.8%) patients received prior radiation for invasive breast
      carcinoma. Most patients underwent total mastectomy with (41%) or without (45%)
      axillary dissection. Regional metastasis to axillary lymph nodes was rare. There
      were 38 recurrences and 27 deaths. The 5-year overall (OS) and recurrence-free
      survival (RFS) rates were 61% (95% confidence interval [CI], 49%-76%) and 44%
      (95% CI, 33%-58%) with estimated medians of 100 and 37 months, respectively. In
      Cox proportional hazards models, OS and RFS were significantly associated only
      with T size and not with patient age, prior radiation, or chemotherapy
      administration. Of 29 patients treated with chemotherapy at recurrence, there
      were 4 complete and 10 partial responses (48%) with an anthracycline-ifosfamide
      or gemcitabine-taxane combination. CONCLUSIONS: Breast angiosarcoma is frequently
      advanced at diagnosis and has a tendency for local-regional recurrence. A
      significant number of responses to chemotherapy was observed in the metastatic
      setting. These data suggest that a multidisciplinary therapeutic approach should
      be employed in high-risk patients with large primary tumors.

PMID- 17541937
TI  - Non-Hodgkin lymphoma of the breast.
AB  - BACKGROUND: Primary lymphoma of the breast has been reported to have a high local
      and central nervous system recurrence (CNS) rate, suggesting the need for
      consolidation radiotherapy and CNS prophylaxis. A retrospective study was done to
      evaluate the institutional experience in this patient population. METHODS: In
      all, 37 patients with lymphoma involving the breast at initial diagnosis and
      managed at Stanford University from 1981-2005 were included. Diagnostic tissue
      biopsies were obtained either from the breast mass or an involved lymph node.
      Treatment and response data, patterns of recurrence, and outcomes were reviewed.
      RESULTS: Diffuse large B cell lymphoma (DLBCL) was the most common histologic
      subtype seen in 18 of 37 (49%) patients. Follicular and marginal zone subtypes
      were seen in 38%. Most patients presented with an incidental breast mass in stage
      I(E) or II(E). Four (11%) patients presented with bilateral breast involvement,
      with only 1 patient presenting with CNS disease. DLBCL patients received
      doxorubicin-based chemotherapy, with 70% receiving involved field radiotherapy
      and a single patient receiving intrathecal therapy. No recurrences occurred in
      the involved breast and a single parenchymal CNS recurrence was recorded. Among
      the DLBCL patients, the 5-year progression-free survival (PFS) was 61%, with a
      median follow-up of 3.8 years (range, 5 months to 19 years) and the 5-year
      overall survival (OS) was estimated at 82%. Patients with indolent lymphoma had
      an estimated 5-year PFS of 76% and an OS of 92%. CONCLUSIONS: DLBCL of the breast
      was successfully treated with doxorubicin-based chemotherapy alone or with
      involved field radiotherapy in an estimated 61% of patients at 5 years. A single
      CNS recurrence was observed in our series of patients, most of whom presented
      with limited disease.

PMID- 17541938
TI  - In vitro generation of superoxide anion by the hemocytes of Macrobrachium
      rosenbergii: possible mechanism and pathways.
AB  - The hemocytes from the giant freshwater prawn Macrobrachium rosenbergii were
      examined for their ability to generate superoxide anion (O(2) (-)) in vitro upon
      exposure to various components derived from microbial cell wall components. Among
      the test molecules, laminarin (a polymer of beta-1, 3 glucans), mannan and LPS
      from five different bacterial species produced a differential response in terms
      of stimulated O(2) (-) production in prawn hemocytes, suggesting the ability of
      the hemocytes to differentiate non-self. This response was almost completely
      inhibited by superoxide dismutase (SOD) suggesting SOD-inhibitable O(2) (-)
      generation by prawn hemocytes. Phorbol 12-myristate 13-acetate (PMA) and Ca
      ionophore led to enhanced O(2) (-) generation by the hemocytes and this suggests
      the possible role of protein kinase C and Ca(2+) ions in such generation.
      Cytochemical analysis using nitroblue tetrazolium (NBT)-staining revealed the
      importance of granular hemocytes in O(2) (-) generation in these prawns.
      Inhibition of O(2) (-) generation by inhibitors of NADPH-oxidase and
      phenoloxidase pathways clearly reveal the involvement of two different pathways
      in non-self stimulated O(2) (-) generation by the prawn hemocytes. These findings
      demonstrate the importance of O(2) (-) generation and role of possible pathways
      in hemocyte mediated cellular immune response of a crustacean.

PMID- 17541939
TI  - LRRC4 inhibits glioblastoma cell proliferation, migration, and angiogenesis by
      downregulating pleiotropic cytokine expression and responses.
AB  - Leucine-rich repeat C4 (LRRC4) has been shown to inhibit glioma cell
      proliferation, however, little is known about the mechanism(s) underlying the
      action of LRRC4. Here, we show that two glioblstoma U251 cell clones stably
      expressing LRRC4 were established. LRRC4 expression significantly inhibited the
      expression of some cytokines and their receptors determined by microarray and
      Western blot assays, and dramatically reduced cytokine-induced AP-1, NF-kB, and
      CyclinD1 activation in glioma cells. Furthermore, LRRC4 expression in glioma
      cells significantly downregulated spontaneous and cytokine-induced expression of
      K-RAS and phosphorylation of c-Raf, ERK, AKT, NF-kBp65, p70S6K, and PKC,
      suggesting that LRRC4 inhibited receptor tyrosine kinase (RTK) signaling
      pathways. Moreover, treatment with bFGF, IGF1, or IGF2 stimulated LRRC4(-/-), but
      not the LRRC4(+), glioma cell proliferation, indicating that LRRC4 mitigated
      cytokine-stimulated proliferation in glioma cells. In addition, treatment of
      LRRC4(-/-) glioma cells with EGF, IGF2, or PDGF promoted long distance
      mobilization, but induced little migration in LRRC4(+) glioma cells, suggesting
      that LRRC4 retarded cytokine-promoted glioma cell migration in vitro. Finally,
      human vessel endothelial cells (ECV304) treated with VEGF grew, aligned and
      formed hollow tube-like structures in vitro. In contrast, LRRC4(+) ECV304 treated
      with VEGF failed to form vessel-tube structures. Collectively, LRRC4 expression
      inhibited the expression of some growth factors, cytokines and their receptors,
      and the capacity of glioma cells responding to cytokine stimulation, leading to
      inhibition of glioma cell proliferation. Conceivably, induction of LRRC4
      expression may provide new intervention for human glioma in the clinic.

PMID- 17541940
TI  - BMP-5 expression increases during chondrocyte differentiation in vivo and in
      vitro and promotes proliferation and cartilage matrix synthesis in primary
      chondrocyte cultures.
AB  - Bone morphogenetic proteins (BMPs) play pivotal roles in bone and cartilage
      growth and repair. Through phenotypes of short-ear (se) mice, which have BMP-5
      mutations, a role for BMP-5 in some specific aspects of skeletogenesis and
      cartilage growth is known. This report examines BMP-5 expression in the growth
      plate and in differentiating cultures of primary chondrocytes, and the effects of
      addition of BMP-5 or its inhibition by anti-BMP-5 antibody in chondrocyte
      cultures. By laser capture microdissection and immunohistochemistry, we found
      that BMP-5 is expressed in proliferating zone (PZ) chondrocytes and that the
      expression increases sharply with hypertrophic differentiation. A similar pattern
      was observed in differentiating cultures of primary chondrocytes, with BMP-5
      expression increasing as cells differentiated, in contrast to other BMPs. BMP-5
      added to cultures increased cell proliferation early in the culture period and
      also stimulated cartilage matrix synthesis. Also, BMP-5 addition to the cultures
      activated phosphorylation of Smad 1/5/8 and p38 MAP kinase and caused increased
      nuclear accumulation of phospho-Smads. Anti-BMP-5 antibody inhibited the
      endogenous BMP-5, reducing cell proliferation and phospho-Smad nuclear
      accumulation. Together, the results demonstrate that BMP-5 is normally an
      important regulator of chondrocyte proliferation and differentiation. Whether
      other BMPs may compensate in BMP-5 loss-of-function mutations is discussed.

PMID- 17541941
TI  - Co-inoculation of prostate cancer cells with U937 enhances tumor growth and
      angiogenesis in vivo.
AB  - Tumor-associated macrophages (TAMs) have been implicated in promoting tumor
      growth and development. Here we present evidence that demonstrates that co
      inoculation of male athymic nude mice with PC-3 prostate cancer cells and U937
      promonocytic cells enhances tumor growth and increases tumor angiogenesis. Male
      athymic nude mice were co-inoculated with PC-3 and U937 cells (control or IL-4
      stimulated) and tumor growth was monitored over time. Immunohistochemical
      analysis of tumor specimens was performed for proliferation markers (e.g., Ki67)
      and the effects of IL-4 stimulation on U937 cells were analyzed for chemokine
      expression. The presence of U937 cells increased the rate of tumor growth in vivo
      and stimulated increased microvascular density within the tumor bed. Stimulation
      of U937 cells with IL-4 resulted in a significant increase in several pro
      angiogenic and pro-tumor chemokines (e.g., CCL2). Co-inoculation increases
      prostate cancer growth via upregulation of chemokines that induce angiogenesis
      within the tumor.

PMID- 17541942
TI  - B220 analysis with the local lymph node assay: proposal for a more flexible
      prediction model.
AB  - The mouse local lymph node assay (LLNA) has been developed and validated for the
      identification of chemicals that have the potential to induce skin sensitisation.
      In common with other predictive test methods the accuracy of the LLNA is not
      absolute and experience has revealed that a few chemicals, including for instance
      a minority of skin irritants, may elicit false-positive reactions in the assay.
      To improve further the performance of the LLNA, and to eliminate or reduce false
      positives, there has been interest in an adjunct method in which the ability of
      chemicals to cause increases in the frequency of B220(+) lymphocytes in skin
      draining lymph nodes is measured. Previous studies suggest that the use of B220
      analyses aligned with the standard LLNA may serve to distinguish further between
      contact allergens and skin irritants. In the original predictive model, chemicals
      were regarded as being skin sensitisers if they were able to induce a 1.25-fold
      or greater increase in the percentage of B220(+) cells within lymph nodes
      compared with concurrent vehicle controls. Although this first prediction model
      has proven useful, in the light of more recent experience, and specifically as a
      consequence of some variability observed in the frequency of B220(+) lymphocytes
      in nodes taken from vehicle control-treated animals, it is timely now to
      reconsider and refine the model. As a result a new prediction model is proposed
      in which reliance on the use of absolute thresholds is reduced, and in which
      small changes in control values can be better accommodated.

PMID- 17541943
TI  - In vitro and in vivo antitumor effect of 5-FU combined with piplartine and
      piperine.
AB  - It has been reported that piplartine and piperine, alkaloid/amide compounds from
      Piper species, show antitumor activities. In the present paper, the effects of
      the combination of 5-fluorouracil (5-FU) with piplartine or piperine was
      determined using in vitro and in vivo experimental models. Hematological and
      biochemical analyses, as well as histopathological and morphological analyses of
      the tumor and the organs, including liver, spleen and kidney, were performed in
      order to evaluate the toxicological aspects associated with different treatments.
      The incubation of tumor cell lines with 5-FU in the presence of piplartine or
      piperine produced an increase in growth inhibition, as observed by lower IC50
      values for 5-FU. These effects were also observed in vivo, where the combination
      with piplartine but not piperine with 5-FU led to a higher tumor growth
      inhibition. The results indicated that either piplartine- or 5-FU-treated animals
      showed a low inhibition rate when they were used individually at low doses of
      28.67% and 47.71%, respectively, but when they were combined at the same dose,
      the inhibition rate increased significantly to 68.04%. The histopathological
      analysis showed that the livers and the kidneys of treated animals were only
      slightly and reversibly affected. Neither the enzymatic activity of transaminases
      nor the urea levels were significantly modified when compared with the control
      group. Hematological analysis showed leukopenia after 5-FU treatment, which was
      reversed by the combined use of piplartine and piperine. These findings indicate
      that piplartine may enhance the therapeutic effectiveness of chemotherapeutic
      drugs, and moreover, this combination could improve immunocompetence hampered by
      5-FU.

PMID- 17541944
TI  - Overlapping human leukocyte antigen class I/II binding peptide vaccine for the
      treatment of patients with stage IV melanoma: evidence of systemic immune
      dysfunction.
AB  - BACKGROUND: MPS160 (GRAMLGTHTMEVTV) is a glycoprotein 100-derived melanoma
      peptide that contains overlapping human leukemic antigen A2-, DR53-, and DQw6
      restricted T-cell epitopes. In preclinical testing, MPS160 demonstrated superior
      immunization and antitumor activity. In this report, the authors present the
      results from a clinical trial that evaluated the safety and immunologic efficacy
      of the MPS160 vaccine in patients with metastatic melanoma. METHODS: Patients
      with stage IV melanoma were randomized to 1 of 3 treatment arms: 1) MPS160 in
      incomplete Freund adjuvant (Montanide ISA-51); 2) MPS160 in Montanide ISA-51 with
      75 microg of granulocyte-macrophage-stimulating factor (GM-CSF); or 3) MPS160 in
      Montanide ISA-51 with 100 microg of GM-CSF. Vaccines were administered every 3
      weeks until patients developed disease progression or severe toxicity. Patients
      were aged >or=18 years with metastatic melanoma and a good performance status.
      Exclusion criteria included pregnancy/nursing, brain metastases, and ongoing
      chemotherapy. Immunologic efficacy was ascertained by using tetramer and
      functional analysis of peripheral blood lymphocytes. RESULTS: None of the 28
      patients exhibited objective tumor responses or severe toxicities. Four patients
      remained progression free for >or=100 days. Immunologic analysis was available
      for 21 patients. Laboratory data demonstrated 1) increased frequency of vaccine
      specific, nonfunctional cytotoxic T lymphocytes in 10 patients; 2) no differences
      in immunization efficacy among the treatment arms; and 3) evidence of systemic
      cytokine/immune dysfunction. CONCLUSIONS: Clinically, the MPS160 vaccine was
      ineffective. Phenotypic (tetramer) evidence of immunization was ineffective
      functionally and most likely was caused by global immune dysfunction, as
      illustrated by abnormal cytokine profiles in peripheral blood. In this report,
      the authors discuss possible implications of the current results on future cancer
      vaccine studies.

PMID- 17541945
TI  - High-dose chemotherapy with autologous stem cell rescue followed by posterior
      fossa irradiation for local medulloblastoma recurrence or progression after
      conventional chemotherapy.
AB  - BACKGROUND: The objective of the current study was to determine the outcome of
      children with local recurrence or progression of medulloblastoma in patients who
      received high-dose chemotherapy (HDC) and posterior fossa (PF) irradiation.
      METHODS: HDC consisted in busulfan at a dose of 600 mg/m(2) and thiotepa at a
      dose of 900 mg/m(2) followed by autologous stem cells transplantation (ASCT). PF
      radiotherapy was delivered at doses from 50 grays (Gy) to 55 Gy on Day +70 after
      ASCT. Twenty-seven patients developed local recurrence of an initially completely
      resected medulloblastoma. Twelve patients had local residual disease after
      surgery and were enrolled into the salvage protocol at the time of local disease
      progression under conventional chemotherapy. RESULTS: Acute toxicity consisted
      mainly in hepatic veno-occlusive disease (33% of patients) and bone marrow
      aplasia. Two toxic deaths (5%) from infections were reported. The 5-year overall
      survival rate after this salvage treatment (OS(5y)) for the 39 children who were
      treated was 68.8% (95% confidence interval [95% CI], 53-81.2%). In the group of
      patients who were treated for local recurrence, the OS(5y) was 77.2% (95% CI,
      58.3-89.1%). Patients with local residual disease who were treated at the time of
      disease progression had an OS(5y) after salvage treatment of only 50% (95% CI,
      25.4-74.6%; P = .09). CONCLUSIONS: The treatment strategy that was used in this
      study had manageable immediate toxicity and resulted in a high overall survival
      rate in the setting of young children with medulloblastoma who developed local
      recurrence or disease progression.

PMID- 17541946
TI  - Angiogenesis by transplantation of HIF-1 alpha modified EPCs into ischemic limbs.
AB  - Hypoxia inducible factor-1 alpha (HIF-1 alpha) is a key determinant of oxygen
      dependent gene regulation in angiogenesis. HIF-1 alpha overexpression may be
      beneficial in cell therapy of hypoxia-induced pathophysiological processes, such
      as ischemic heart disease. To address this issue, human peripheral blood
      mononuclear cells (PBMNCs) were induced to differentiate into endothelial
      progenitor cells (EPCs), and then were transfected with either an HIF-1 alpha
      expressing or a control vector and cultured under normoxia or hypoxia. Hypoxia
      induced HIF-1 alpha mRNA and protein expression was increased after HIF-1 alpha
      transfection. This was accompanied by VEGF mRNA induction and increased VEGF
      secretion. Hypoxia-stimulated VEGF mRNA induction was significantly abrogated by
      HIF-1 alpha-specific siRNA. Functional studies showed that HIF-1 alpha
      overexpression further promoted hypoxia-induced EPC differentiation,
      proliferation and migration. The expressions of endothelial cell markers CD31,
      VEGFR2 (Flk-1) and eNOS as well as VEGF and NO secretions were also increased.
      Furthermore, in an in vivo model of hindlimb ischemia, HIF-1 alpha-transfected
      EPCs homed to the site of ischemia. A higher revascularization potential was also
      demonstrated by increased capillary density at the injury site. Our results
      revealed that endothelial progenitor cells ex vivo modification by hypoxia
      inducible factor-1 alpha gene transfection is feasible and may offer significant
      advantages in terms of EPC expansion and treatment efficacy.

PMID- 17541947
TI  - Skeletal stem/osteoprogenitor cells: current concepts, alternate hypotheses, and
      relationship to the bone remodeling compartment.
AB  - Plastic adherent bone marrow stromal cells have become synonymous with skeletal
      stem cells, and perhaps rightfully so, as these cells have been extremely well
      characterized over the past four decades, since their original description by
      Friedenstein. However, although this cell population is useful as an experimental
      model of precursors for osteoblasts and other mesenchymal lineages, the precise
      role of bone marrow stromal cells in bone remodeling, fracture repair, or repair
      of non-skeletal tissues remains unclear. Moreover, there is a conceptual problem
      in terms of postulating that these cells are osteoblast precursors at sites of
      bone remodeling on trabecular surfaces adjacent to red marrow and yet having to
      posit potentially entirely different mechanisms for the origins of osteoblasts at
      sites of cortical bone remodeling distant from red marrow. Thus, the
      identification and characterization in recent years of non-adherent stem and
      osteoprogenitor cells in the bone marrow, of similar cells in the peripheral
      circulation, and of stem/osteoprogenitor cells arising either from the
      perivascular compartment (pericytes) or within the developing vascular wall
      itself, has suggested alternative candidate cell populations that may help to
      resolve the problem of postulating different mechanisms of remodeling in
      trabecular versus cortical bone. When coupled with our evolving understanding of
      the bone remodeling compartment (BRC), a closed cavity penetrated by capillaries
      which appears to be the site of remodeling in both trabecular and cortical bone,
      it is likely that our conceptual understanding of the fundamental mechanisms of
      bone remodeling will need to be modified.

PMID- 17541948
TI  - Yeast N(alpha)-terminal acetyltransferases are associated with ribosomes.
AB  - N-terminal acetylation is one of the most common modifications, occurring on the
      vast majority of eukaryotic proteins. Saccharomyces cerevisiae contains three
      major NATs, designated NatA, NatB, and NatC, with each having catalytic subunits
      Ard1p, Nat3p, and Mak3p, respectively. Gautschi et al. (Gautschi et al. [2003]
      Mol Cell Biol 23: 7403) previously demonstrated with peptide crosslinking
      experiments that NatA is bound to ribosomes. In our studies, biochemical
      fractionation in linear sucrose density gradients revealed that all of the NATs
      are associated with mono- and polyribosome fractions. However only a minor
      portion of Nat3p colocalized with the polyribosomes. Disruption of the
      polyribosomes did not cause dissociation of the NATs from ribosomal subparticles.
      The NAT auxiliary subunits, Nat1p and Mdm20p, apparently are required for
      efficient binding of the corresponding catalytic subunits to the ribosomes.
      Deletions of the genes corresponding to auxiliary subunits significantly diminish
      the protein levels of the catalytic subunits, especially Nat3p, while deletions
      of the catalytic subunits produced less effect on the stability of Nat1p and
      Mdm20p. Also two ribosomal proteins, Rpl25p and Rpl35p, were identified in a TAP
      affinity purified NatA sample. Moreover, Ard1p copurifies with Rpl35p-TAP. We
      suggest that these two ribosomal proteins, which are in close proximity to the
      ribosomal exit tunnel, may play a role in NatA attachment to the ribosome.

PMID- 17541949
TI  - Matrigel-induced acinar differentiation is followed by apoptosis in HSG cells.
AB  - It has been shown that a human salivary gland cell line (HSG) is capable of
      differentiation into gland-like structures, though little is known of how
      morphological features are formed or controlled. Here we investigated the changes
      in cell proliferation and apoptosis upon terminal differentiation of HSG cells in
      Matrigel, an extracellular matrix derivative. Changes in the expression of
      survivin, a prominent anti-apoptotic factor, and caspase-3, a key apoptotic
      factor were also measured. In order to better understand the involvement of key
      signal transduction pathways in this system we pharmacologically blocked the
      activity of tyrosine kinase, nuclear factor kappa B(NF kappa B), protein kinase C
      (PKC), phosphatidylinositol 3-kinase (PI3K) and matrix metalloproteases (MMP).
      Results of these studies demonstrate that cytodifferentiation of HSG cells to an
      acinar phenotype is accompanied first by a decrease of cell proliferation and
      then by a massive programmed cell death, affected by multiple signal transduction
      pathways. Thus, Matrigel alone is insufficient for the full maturation and long
      term survival of the newly formed acini: the presence of other factors is
      necessary to complete the acinar differentiation of HSG cells.

PMID- 17541950
TI  - Polymorphisms in the homeobox gene OTX2 may be a risk factor for bipolar
      disorder.
AB  - We investigated the possible involvement of OTX2, a homeobox gene crucial for
      forebrain development, in the pathogenesis of schizophrenia and bipolar disorder.
      The disruption of this gene results in cortical malformations and causes
      serotonergic and dopaminergic cells in the midbrain to be expressed in aberrant
      locations. Resequencing of DNA from OTX2 exons and surrounding introns from 60
      individuals (15 schizophrenia, 15 bipolar disorder, 15 depression, and 15
      control) revealed two intronic polymorphisms, rs2277499 (C/T) and rs28757218
      (G/T), but no other variations. The minor allele of rs2277499 (T) did not
      associate with clinical diagnosis. However, using a Taqman genotyping assay, we
      found the rs28757218 minor allele (T) in 30 out of 720 (4.2%) individuals with
      bipolar disorder but only in 6 out of 526 (1.1%) control individuals (odds ratio
      3.5, 95% confidence interval 1.4-10.4, P = 0.003). On the other hand, the
      rs28757218 minor allele was only found in 6 out of 458 (1.3%) individuals with
      schizophrenia. All individuals with the rs28757218 polymorphism were heterozygous
      for the allele. Based on this positive case-control association finding, we
      conclude that variations in OTX2 might confer risk for the development of bipolar
      disorder.

PMID- 17541951
TI  - PKC-zeta expression is lower in osteoblasts from arthritic patients: IL1-beta and
      TNF-alpha induce a similar decrease in non-arthritic human osteoblasts.
AB  - Protein kinase C (PKC) is a family of enzymes detected in a diverse range of cell
      types where they regulate various cellular functions such as proliferation,
      differentiation, cytoskeletal remodelling, cytokine production, and receptor
      mediated signal transduction. In this study we have analyzed the expression of 11
      PKC isoforms (-alpha, -beta(I), -beta(II), -gamma, -delta, -eta, -theta, 
      epsilon, -zeta, -iota/lambda, and -micro) in osteoblasts from patients with
      osteoarthritis (OA) and rheumatoid arthritis (RA) in comparison with osteoblasts
      from post-traumatic (PT) patients. By Western blotting analysis, nine isoforms, 
      alpha, -beta(I), -beta(II), -delta, -theta, - epsilon, -zeta, - iota/lambda, and 
      micro, were detected in osteoblasts. In RA and OA patients, PKC -theta and -micro
      were greater expressed whereas PKC-epsilon and -zeta decreased when compared with
      normal cells. The subcellular distribution and quantitative differences were
      confirmed by immuno-electron microscopy. Furthermore, we demonstrated that
      treatment with the proinflammatory cytokines, IL-1beta and TNF-alpha,
      significantly decreased PKC-zeta expression in PT osteoblasts. This suggests that
      proinflammatory cytokines can modulate the expression of this PKC isoform in
      osteoblasts in a way which is similar to changes detected in arthritic patients.

PMID- 17541952
TI  - Whey acidic protein (WAP) regulates the proliferation of mammary epithelial cells
      by preventing serine protease from degrading laminin.
AB  - Whey acidic protein (WAP) is a major whey protein in milk that has structural
      similarity to the family of serine protease inhibitors with WAP motif domains
      characterized by a four-disulfide core. We previously reported that enforced
      expression of the mouse WAP transgene in mammary epithelial cells inhibits their
      proliferation in vitro and in vivo by means of suppressing cyclin D1 expression
      (Nukumi et al., 2004, Dev Biol 274: 31-44). This study was conducted in order to
      clarify the molecular mechanism of the inhibitory function of WAP in HC11 cells,
      a mammary epithelial cell line. The assembly of laminin, a component in the
      extracellular matrix, was much more prominent around WAP-clonal HC11 cells that
      stably expressed the WAP transgene than around mock-clonal HC11 cells, and the
      proliferation of WAP-clonal HC11 cells was particularly inhibited in the presence
      of laminin. A laminin degradation assay demonstrated that WAP inhibited the
      activity of the pancreatic elastase-mediated cleavage of laminin B1 and the
      phosphorylation of ERK1/2. ERK1/2 phosphorylation was blocked by an inhibitor of
      the epidermal growth factor (EGF) receptor AG1478. Treatment with pancreatic
      elastase was found to enhance the proliferation of mock-clonal HC11 cells, but
      had no effect on that of WAP-clonal HC11 cells. The proliferation of WAP-clonal
      HC11 cells was recovered by the addition of exogenous EGF. We concluded that WAP
      plays some role in regulating the proliferation of mammary epithelial cells by
      preventing elastase-type serine protease from carrying out laminin degradation
      and thereby suppressing the MAP kinase signal pathway.

PMID- 17541953
TI  - The fast track day hospital maintaining clinical improvement in community
      setting.

PMID- 17541954
TI  - Sperm nucleosomes disassembly is a requirement for histones proteolysis during
      male pronucleus formation.
AB  - We had previously reported that a cysteine-protease catalyzes the sperm histones
      (SpH) degradation associated to male chromatin remodeling in sea urchins. We
      found that this protease selectively degraded the SpH leaving maternal cleavage
      stage (CS) histone variants unaffected, therefore we named it SpH-protease. It is
      yet unknown if the SpH-protease catalyzes the SpH degradation while these
      histones are organized as nucleosomes or if alternatively these histones should
      be released from DNA before their proteolysis. To investigate this issue we had
      performed an in vitro assay in which polynucleosomes were exposed to the active
      purified protease. As shown in this report, we found that sperm histones
      organized as nucleosomes remains unaffected after their incubation with the
      protease. In contrast the SpH unbound and free from DNA were readily degraded.
      Interestingly, we also found that free DNA inhibits SpH proteolysis in a dose
      dependent manner, further strengthening the requirement of SpH release from DNA
      before in order to be degraded by the SpH-protease. In this context, we have also
      investigated the presence of a sperm-nucleosome disassembly activity (SNDA) after
      fertilization. We found a SNDA associated to the nuclear extracts from zygotes
      that were harvested during the time of male chromatin remodeling. This SNDA was
      undetectable in the nuclear extracts from unfertilized eggs and in zygotes
      harvested after the fusion of both pronuclei. We postulate that this SNDA is
      responsible for the SpH release from DNA which is required for their degradation
      by the cysteine-protease associated to male chromatin remodeling after
      fertilization.

PMID- 17541955
TI  - Antibody-mediated cell labeling of peripheral T cells with micron-sized iron
      oxide particles (MPIOs) allows single cell detection by MRI.
AB  - Labeling cells with iron oxide is a useful tool for MRI based cellular imaging.
      Here it is demonstrated that peripheral rat T cells can be labeled in whole
      blood, in vitro, with streptavidin-coated micron-sized iron oxide particles
      (MPIOs), achieving iron concentrations as high as 60 pg iron per cell. This is 30
      times the amount of labeling reported with ultrasmall particles of iron oxide
      (USPIOs). Labeling was mediated by use of a biotinylated anti-CD5 antibody, which
      is specific for peripheral T cells. Such labeling allowed the in vitro detection
      of single lymphocytes by MRI, using conditions well suited for in vivo animal
      work. Electron microscopic analysis demonstrated that MPIOs remained largely
      extracellular after labeling, with some evidence of intracellular uptake. Cell
      viability and early and late cytokine release studies showed no significant
      differences between labeled and unlabeled cells. Therefore, the use of MPIOs for
      achieving high iron concentrations for cellular MRI is potentially an effective
      new modality for non-invasive imaging of lymphocytes.

PMID- 17541957
TI  - The participation of the Na+-Ca2+ exchanger in primary cardiac myofibroblast
      migration, contraction, and proliferation.
AB  - Cardiac ventricular myofibroblast motility, proliferation, and contraction
      contribute to post-myocardial infarct wound healing, infarct scar formation, and
      remodeling of the ventricle remote to the site of infarction. The Na+-Ca2+
      exchanger (NCX1) is involved in altered calcium handling in cardiac myocytes
      during cardiac remodeling associated with heart failure, however, its role in
      cardiac myofibroblast cell function is unexplored. In this study we investigated
      the involvement of NCX1 as well as the role of non-selective-cation channels
      (NSCC) in cardiac myofibroblast cell function in vitro. Immunofluorescence and
      Western blots revealed that P1 cells upregulate alpha-smooth muscle actin
      (alphaSMA) and embryonic smooth muscle myosin heavy chain (SMemb) expression.
      NCX1 mRNA and proteins as well as Ca(v)1.2a protein are also expressed in P1
      myofibroblasts. Myofibroblast motility in the presence of 50 ng/ml PDGF-BB was
      blocked with AG1296. Myofibroblast motility, contraction, and proliferation were
      sensitive to KB-R7943, a specific NCX1 reverse-mode inhibitor. In contrast, only
      proliferation and contraction, but not motility were sensitive to nifedipine,
      while gadolinium (NSCC blocker) was only associated with decreased motility. ML-7
      treatment was associated with inhibition of the chemotactic response and
      contraction. Thus cardiac myofibroblast chemotaxis, contraction, and
      proliferation were sensitive to different pharmacologic treatments suggesting
      that regulation of transplasmalemmal calcium movements may be important in growth
      factor receptor-mediated processes. NCX1 may represent an important moiety in
      suppression of myofibroblast functions.

PMID- 17541956
TI  - Estrogen-TGFbeta cross-talk in bone and other cell types: role of TIEG, Runx2,
      and other transcription factors.
AB  - It is well established that E(2) and TGFbeta have major biological effects in
      multiple tissues, including bone. The signaling pathways through which these two
      factors elicit their effects are well documented. However, the interaction
      between these two pathways and the potential consequences of cross-talk between
      E(2) and TGFbeta continue to be elucidated. In this prospectus, we present known
      and potential roles of TIEG, Runx2, and other transcription factors as important
      mediators of signaling between these two pathways.

PMID- 17541958
TI  - Impact of tobacco-smoke on key signaling pathways in the innate immune response
      in lung macrophages.
AB  - Many of the healthcare consequences of cigarette smoking could be due to its
      ability to compromise the immune system, and in respiratory diseases like chronic
      obstructive pulmonary disease (COPD), a constant low level of infection could be
      responsible for some of the symptoms/pathology. The aim was to assess the impact
      of cigarette smoke (CS) on the release of innate effector cytokines in THP-1
      cells and human lung macrophages, and to determine the molecular mechanism behind
      the altered response. Cells were exposed to CS with and without endotoxin
      stimulus, cytokines, glutathione, mitogen-activated protein kinase (MAPK)
      phosphorylation, IkappaB kinase-2 (IKK-2) activity, nuclear factor kappa B (NF
      kappaB), and activator protein-1 (AP-1) pathway activation was measured. Attempts
      were made to mimic or block the effect of CS by using nicotine, nitric oxide
      donors/inhibitors, prostanoid inhibitors, and anti-oxidants. Results showed that
      CS initially delayed the production of "innate" cytokines (e.g., IL-1beta and IL
      6) and reduced glutathione levels. This was associated with a reduction in NF
      kappaB pathway activation, which suggested a causative link. CS also increased
      the phosphorylation of MAPK's and the production of IL-8 but interestingly only
      in stimulated cells. Exogenous glutathione treatment reversed both these effects
      of CS, which suggests that this molecule may play a central role. In conclusion,
      this data provides a novel mechanistic explanation for why smokers have increased
      prevalence/severity of respiratory infections. In addition, the suppression of
      the innate response is accompanied by an increase in the neutrophil
      chemoattractant, IL-8, which may suggest a link to the pathogenesis of smoking
      related inflammatory disease.

PMID- 17541959
TI  - The role of androgen in determining differentiation and regulation of androgen
      receptor expression in the human prostatic epithelium transient amplifying
      population.
AB  - Abnormal differentiation in epithelial stem cells or their immediate
      proliferative progeny, the transiently amplifying population (TAP), may explain
      malignant pathogenesis in the human prostate. These models are of particular
      importance as differing sensitivities to androgen among epithelial cell
      subpopulations during differentiation are recognised and may account for
      progression to androgen independent prostate cancer. Androgens are crucial in
      driving terminal differentiation and their indirect effects via growth factors
      from adjacent androgen responsive stroma are becoming better characterised.
      However, direct effects of androgen on immature cells in the context of a
      prostate stem cell model have not been investigated in detail and are studied in
      this work. In alpha2beta1hi stem cell enriched basal cells, androgen analogue
      R1881 directly promoted differentiation by the induction of differentiation
      specific markers CK18, androgen receptor (AR), PSA and PAP. Furthermore,
      treatment with androgen down-regulated alpha2beta1 integrin expression, which is
      implicated in the maintenance of the immature basal cell phenotype. The
      alpha2beta1hi cells were previously demonstrated to lack AR expression and the
      direct effects of androgen were confirmed by inhibition using the anti-androgen
      bicalutamide. AR protein expression in alpha2beta1hi cells became detectable when
      its degradation was repressed by the proteosomal inhibitor MG132. Stratifying the
      alpha2beta1hi cells into stem (CD133(+)) and transient amplifying population
      (TAP) (CD133(-)) subpopulations, AR mRNA expression was found to be restricted to
      the CD133(-) (TAP) cells. The presence of a functional AR in the TAP, an androgen
      independent subpopulation for survival, may have particular clinical significance
      in hormone resistant prostate cancer, where both the selection of immature cells
      and functioning AR regulated pathways are involved.

PMID- 17541966
TI  - Iron withholding as an innate immune mechanism in the American alligator
      (Alligator mississippiensis).
AB  - Pathogenic microbes require Fe and Zn for growth and proliferation. Upon
      infection, microbes produce proteins, called sidephores, designed to strip serum
      divalent metals away from host proteins. Higher vertebrates respond to infection
      by increasing the expression of proteins that sequester serum iron away from
      bacteria. As a result, host plasma Fe levels decrease during the initial phases
      of infection. This study was conducted to determine if the American alligator, an
      ancient reptile, exhibits the same innate immune mechanism to protect against in
      vivo microbial proliferation. Intraperitoneal injection of juvenile captive
      alligators with bacterial lipopolysaccharide (LPS) resulted in a time-dependent
      decrease in plasma Fe, as determined by inductively coupled plasma emission
      spectroscopy. Plasma Fe levels decreased by 5.9, 10.6, and 18.6% relative to
      untreated control levels at 3, 6, and 12 hr post-injection, respectively, and
      remained decreased by 12.0% at 48 hr. Alligators injected with pyrogen-free
      saline did not exhibit statistically significant changes in plasma Fe
      concentrations at any time point observed. In contrast, serum Zn and Cu remained
      unchanged relative to untreated controls. To insure that the decreases in plasma
      Fe were not due to the repeated blood collections during the course of the
      kinetic study, another experiment was conducted in which plasma metals were
      measured at 24 hr post-injection. Once again, plasma Fe was reduced by 30.2%,
      whereas Zn and Cu did not exhibit appreciable changes. These results show that
      alligators exhibit low plasma Fe levels during an inflammatory response induced
      by bacterial lipopolysaccharide.

PMID- 17541967
TI  - Hox genes in the antarctic polyplacophoran Nuttallochiton mirandus.
AB  - Hox genes are conserved across all bilaterians and encode transcription factors
      involved in the formation of the anteroposterior axis during embryo development.
      Differences in homeotic gene evolution have been observed not only between
      deuterostomes and protostomes, but also between the two large protostome clades,
      Ecdysozoa and Lophotrochozoa.Among lophotrochozoans, the phylum Mollusca displays
      high diversity of body plans, ranging from the wormlike appearance of
      aplacophorans to the complex body plan of cephalopods. Using a PCR-based method,
      we were able to identify eight Hox genes in the polyplacophoran Nuttallochiton
      mirandus, two orthologous to the anterior class (lab, pb), four to the central
      class (Scr, Lox5, Antp, Lox2) and two to the posterior class (Post-1, Post-2).
      Comparison with the results obtained in other molluscs seems to confirm the
      conservation of Hox genes in this phylum in terms of both presence and
      characteristics.

PMID- 17541968
TI  - Metastatic bone disease: a 36-year single centre trend-analysis of patients
      admitted to a tertiary orthopaedic surgical department.
AB  - BACKGROUND AND OBJECTIVES: The treatment and outcome of primary malignant bone
      tumours has changed with the advances in diagnostic and treatment modalities. A
      trend-analysis on a large cohort of patients with metastatic bone disease was
      performed. METHODS: A retrospective chart review of all cases with metastatic
      bone disease admitted to a single tertiary orthopaedic referral centre,
      registered with the Vienna Bone and Soft Tissue Tumour Registry between 1968 and
      2003 was conducted. For trend-analysis of frequency, survival, primary site,
      treatment methods, and others, the 36-year study duration was divided into four
      periods. RESULTS: The study identified 601 females and 580 males (mean: 60 years)
      with metastatic bone disease. The most common metastases were secondary to breast
      cancer (n = 275; 23%) and renal cell carcinoma (n = 242; 21%) and the majority
      were located in the femur (n = 332; 28%) and spine (n = 348; 29%). Overall, the
      proportion of patients who underwent surgery decreased. At follow-up, 887 (75%)
      patients were verified to have died of their disease. CONCLUSIONS: Over the 36
      year period, the frequency of bone metastases has increased at our centre.
      Although survival increased over time, the difference was not significant; this
      was most likely attributable to the seriousness of cases referred to our tertiary
      care centre.

PMID- 17541969
TI  - Integration of wings and their eyespots in the speckled wood butterfly Pararge
      aegeria.
AB  - We investigated both the phenotypic and developmental integration of eyespots on
      the fore- and hindwings of speckled wood butterflies Pararge aegeria. Eyespots
      develop within a framework of wing veins, which may not only separate eyespots
      developmentally, but may at the same time also integrate them by virtue of being
      both signalling sources and barriers during eyespot development. We therefore
      specifically investigated the interaction between wing venation patterns and
      eyespot integration. Phenotypic covariation among eyespots was very high, but
      only eyespots in neighbouring wing cells and in homologous wing cells on
      different wing surfaces were developmentally integrated. This can be explained by
      the fact that the wing cells of these eyespots share one or more wing veins. The
      wing venation patterns of fore- and hindwings were highly integrated, both
      phenotypically and developmentally. This did not affect overall developmental
      integration of the eyespots. The adaptive significance of integration patterns is
      discussed and more specifically we stress the need to conduct studies on
      phenotypic plasticity of integration.

PMID- 17541970
TI  - Melanocytes in the testes of Eupemphix nattereri (Anura, Leiuperidae):
      histological, stereological, and ultrastructural aspects.
AB  - Ectothermic vertebrates have a well-developed system of melanin-containing cells,
      which localize in several organs and tissues and compose an extracutaneous
      pigmentary system. This research aimed at characterizing histological and
      ultrastructural patterns of pigmented cells in the testes of the anura Eupemphix
      nattereri (Steindachner, 1963), including the stereological and quantitative
      evaluation of this cell type in the gonads. Ten adult males were collected in
      Nova Itapirema, Sao Paulo, Brazil, and submitted to morphological studies with
      light and transmission electron microscopy. The testis presents a great number of
      large cells with many brown granules and long cytoplasmic processes. The
      pigmented cells found in the testis are structurally similar to melanocytes,
      characterized by large amounts of melanosomes. The cells may be in intimate
      contact with the same cell type, with myoid cells surrounded by a large amount of
      collagen fibers, Leydig cells, and next to fibroblasts. The distribution and
      amount of extracutaneous melanocytes is variable when other organs and membranes
      are analyzed, allowing the establishment of species-specific patterns for the
      extracutaneous pigmentary system.

PMID- 17541971
TI  - Mouse sperm rosette: assembling during epididymal transit, in vitro disassemble,
      and oligosaccharide participation in the linkage material.
AB  - In many mammals, sperm associations had been observed, but not in the mouse. In
      this work, mouse sperm rosettes are morphologically described inside the
      epididymis and during its dissolution in a culture medium. Also characterized are
      the saccharides present in the linking material. Sperm association and other
      epididymal actions are supported by sperm during epididymal transit and are
      verified at the caudal region, suggesting a relation between epididymal transit
      and sperm maturation. In drops of epididymal content obtained from distal
      (cauda), but not from proximal (caput and corpus) regions; dissolved in culture
      medium, rosettes appear to be 10 to 15 motile sperm joined by their heads. After
      3 min, sperm progressively detach, disassembling the rosette. These structures
      are studied by several techniques, including optic, electronic (scanning electron
      microscopy and transmission electron microscopy), and video microscopy. At the
      ultrastructural level, a dense network of electron-dense material was observed
      between sperm heads, joining them. Based on previous works in rat, several
      lectins were used to characterize the type of saccharides present in this linking
      material. To avoid the contact between sperm and epididymal fluid from distal
      region--that probably exerts an influence on sperm association--a ligature was
      placed between caput and corpus. This epididymal content isolated from caput did
      not display any rosettes after 28 days.

PMID- 17541972
TI  - Effect of prolactin and bromocriptine on the population of prostate
      neuroendocrine cells from intact and cyproterone acetate-treated rats:
      stereological and immunohistochemical study.
AB  - This work deals with the quantification of serotonin-immunoreactive prostate
      neuroendocrine cells (NECs) in rats exposed to prolactin in normal, cyproterone
      acetate-exposed, and bromocriptine-exposed animals to establish the possible
      influence of prolactin with or without androgenic blockade on this cell
      population. Thirty male peripubertal Sprague-Dawley rats were grouped as controls
      (CT) and those treated with cyproterone acetate (CA), cyproterone acetate plus
      prolactin, cyproterone acetate plus bromocriptine, prolactin (PL), and
      bromocriptine (BC). The volume of ductal epithelium (Vep) and total number (NSER)
      of the NECs serotonin-immunoreactive were measured. NECs were detected in the
      periurethral ducts. Compared to CT, Vep was increased in PL and BC and NSER was
      decreased in CA and increased in the prolactin or bromocriptine groups. The
      androgenic blockade decreases NSER in rat prostate; PL induces in normal and
      cyproterone acetate-treated rats the increase of NSER; and BC exerts a local
      effect over the prostate similar to that described for PL.

PMID- 17541973
TI  - The proteasome regulates the interaction between Cx43 and ZO-1.
AB  - Gap junction (GJ) intercellular communication (GJIC) is vital to ensure proper
      cell and tissue function. GJ are multimeric structures composed of proteins
      called connexins. Modifications on stability or subcellular distribution of
      connexins have a direct impact on the extent of GJIC. In this study we have
      investigated the role of the proteasome in regulation of connexin 43 (Cx43)
      internalization. Although the participation of both the proteasome and lysosome
      has long been suggested in Cx43 degradation, the molecular mechanisms whereby
      proteasome contributes to regulate Cx43 internalization and intercellular
      communication are still unclear. The results presented in this study envision a
      new mechanism whereby proteasome regulates GJIC by modulating interaction between
      Cx43 and ZO-1. Immunoprecipitation experiments, in the presence of proteasome
      inhibitors, together with immunofluorescence data indicate that the proteasome
      regulates interaction between Cx43 and ZO-1. Overexpression of the PDZ2 domain of
      ZO-1 and the expression of Cx-43 fused in frame with a V5/HIS tag, suggest that
      interaction between the two proteins occurs through the PDZ2 domain of ZO-1 and
      the C-terminus of Cx43. When interaction between Cx43 and ZO-1 is reduced, as in
      the presence of proteasome inhibitors, Cx43 accumulates, forming large GJ plaques
      at plasma membrane. Data presented in this article suggest a new pathway whereby
      alterations in proteasome activity may impact on GJIC as well as on non
      junctional communication with extracellular environment, contributing to cell and
      tissue dysfunction.

PMID- 17541974
TI  - Whole genome association studies: deciding when persistence becomes
      perseveration.

PMID- 17541975
TI  - The SCID PTSD module's trauma screen: validity with two samples in detecting
      trauma history.
AB  - We investigated the posttraumatic stress disorder (PTSD) module's trauma screen
      of the Structured Clinical Interview for DSM-IV (SCID), a single-item traumatic
      event history query. Compared to the Stressful Life Events Screening
      Questionnaire (SLESQ), the SCID trauma screen was 76% sensitive in identifying
      trauma histories in 199 medical patients (correctly ruling out 67%) but only 66%
      sensitive in 253 college students (ruling out 87%). A modified, more behaviorally
      specific SCID trauma screen (M-SCID) yielded poorer results in identifying trauma
      among 245 additional college students. Based on probable PTSD diagnoses (PTSD
      Symptom Scale), using the SCID screen instead of the SLESQ, 3% (M-SCID screen) to
      11-14% (standard SCID) of PTSD cases were missed due to not having a trauma
      history. Our results lend support to previous research establishing the SCID
      trauma screen as a useful screening device in settings where a more comprehensive
      trauma screen is not possible.

PMID- 17541976
TI  - Antibacterial activity of contact lenses bearing surface-immobilized layers of
      intact liposomes loaded with levofloxacin.
AB  - In vitro methods to evaluate antibacterial activity were used with contact lenses
      bearing levofloxacin-loaded liposomes developed for the prevention and treatment
      of bacterial ocular infections such as keratitis. Levofloxacin was incorporated
      into liposomes before these intact liposomes were immobilized onto the surfaces
      of soft contact lenses using a multilayer immobilization strategy. The release of
      levofloxacin from contact lenses bearing 2, 5, and 10 layers of liposomes into a
      saline buffer at 37 degrees C was monitored by fluorescence. The levofloxacin
      release, as a function of time, was described by a mechanism taking into account
      two independent first-order kinetic models. The total release of levofloxacin
      from the contact lenses was completed within 6 days. The release of levofloxacin
      from contact lenses bearing 10 layers of liposomes and subsequently soaked
      overnight in a levofloxacin solution was also studied and compare to that of
      dried contact lenses without any chemical modification rehydrated in a
      levofloxacin solution. The antibacterial activity of the liposome-coated contact
      lenses against Staphylococcus aureus was evaluated by measuring (i) the diameters
      of the inhibition zone on an agar plate and (ii) the optical density using a
      broth assay. The liposome-coated lenses showed an antibacterial activity both on
      agar and in broth following 24 h. When initial bacteria inocula were equal or
      below 10(6) CFU/mL, all the bacteria were inhibited within 2 h. When using
      initial bacteria inocula of 10(8) CFU/mL, an initial burst release provided by
      soaking the liposomal lenses was required for the first hours to inhibit bacteria
      growth.

PMID- 17541977
TI  - X-ray powder diffractometry of intact film coated tablets--an approach to monitor
      the physical form of the active pharmaceutical ingredient during processing and
      storage.
AB  - The antiviral compound, 2-amino-6-(4-methoxyphenylthio)-9-[2
      (phosphonomethoxy)ethyl]purine bis(2,2,2-trifluoroethyl)ester (MCC-478), can
      exist in several anhydrous polymorphic forms and also as a hemihydrate. The XRD
      patterns of the tablets, containing each form of the active pharmaceutical
      ingredient (API), revealed at least one peak unique to each form. A
      semiquantitative microdiffractometric method was developed to nondestructively
      characterize the physical form of the API in intact film-coated tablets. This was
      accomplished even though the weight fraction of the API was <0.2 and that of
      mannitol, a highly crystalline excipient, was approximately 0.6. The method was
      used to determine the effect of aqueous film-coating process on the physical form
      of the API. The final dosage form was also monitored following storage at 40
      degrees C/75% RH for 6 months. There was no phase transformation of the API
      either due to the film-coating process or following accelerated storage. This
      technique has potential utility not only for process control during manufacture,
      but also for the quality control of the final product.

PMID- 17541978
TI  - Anxiety disorders and risk for suicide attempts: findings from the Baltimore
      Epidemiologic Catchment area follow-up study.
AB  - Our objective was to determine whether the presence of an anxiety disorder was a
      risk factor for future suicide attempts. Data were drawn from the 13-year follow
      up Baltimore Epidemiological Catchment Area survey (n=1,920). Multiple logistic
      regression analysis was used to determine the association between baseline
      anxiety disorders (social phobia, simple phobia, obsessive-compulsive disorder,
      panic attacks, or agoraphobia) and subsequent onset suicide attempts. The
      presence of one or more anxiety disorders at baseline was significantly
      associated with subsequent onset suicide attempts (adjusted odds ratio 2.20, 95%
      confidence interval 1.04-4.64) after controlling for sociodemographic variables
      and all baseline mental disorders assessed in the survey. These findings suggest
      that anxiety disorders are independent risk factors for suicide attempts, and
      underscore the importance of anxiety disorders as a serious public health
      problem.

PMID- 17541979
TI  - Noncontact photo-acoustic defect detection in drug tablets.
AB  - Quality assurance monitoring is of great importance in the pharmaceutical
      industry for the reason that if defects such as coating layer irregularities,
      internal cracks, and delamination are present in a drug tablet, the desired dose
      delivery and bioavailability can be compromised. The U.S. Food and Drug
      Administration (FDA) established the Process Analytical Technology (PAT)
      initiative, in order to ensure efficient quality monitoring at each stage of the
      manufacturing process by the integration of analysis systems into the evaluation
      procedure. Improving consistency and predictability of tablet action by improving
      quality and uniformity of tablet coatings as well as ensuring core integrity is
      required. An ideal technique for quality monitoring would be noninvasive,
      nondestructive, have a short measurement time, intrinsically safe, and relatively
      inexpensive. In the proposed acoustic system, a pulsed laser is utilized to
      generate noncontact mechanical excitations and interferometric detection of
      transient vibrations of the drug tablets is employed for sensing. Two novel
      methods to excite vibrational modes in drug tablets are developed and employed:
      (i) a vibration plate excited by a pulsed-laser and (ii) pulsed laser-induced
      plasma generated shockwave expansion. Damage in coat and/or core of a tablet
      weakens its mechanical stiffness and, consequently, affects its acoustic response
      to an external dynamic force field. From the analysis of frequency spectra and
      the time-frequency spectrograms obtained under both mechanisms, it can be
      concluded that defective tablets can be effectively differentiated from the
      defect-free ones and the proposed proof-of-concept techniques have potential to
      provide a technology platform to be used in the greater PAT effort.

PMID- 17541980
TI  - Pristimerin induces apoptosis by targeting the proteasome in prostate cancer
      cells.
AB  - Pristimerin is a natural product derived from the Celastraceae and
      Hippocrateaceae families that were used as folk medicines for anti inflammation
      in ancient times. Although it has been shown that pristimerin induces apoptosis
      in breast cancer cells, the involved mechanism of action is unknown. The purpose
      of the current study is to investigate the primary target of pristimerin in human
      cancer cells, using prostate cancer cells as a working model. Nucleophilic
      susceptibility and in silico docking studies show that C6 of pristimerin is
      highly susceptible towards a nucleophilic attack by the hydroxyl group of N
      terminal threonine of the proteasomal chymotrypsin subunit. Consistently,
      pristimerin potently inhibits the chymotrypsin-like activity of a purified rabbit
      20S proteasome (IC50 2.2 micromol/L) and human prostate cancer 26S proteasome
      (IC50 3.0 micromol/L). The accumulation of ubiquitinated proteins and three
      proteasome target proteins, Bax, p27 and I kappa B-alpha, in androgen receptor
      (AR)-negative PC-3 prostate cancer cells supports the conclusion that proteasome
      inhibition by pristimerin is physiologically functional. This observed proteasome
      inhibition subsequently led to the induction of apoptotic cell death in a dose-
      and kinetic-dependent manner. Furthermore, in AR-positive, androgen-dependent
      LNCaP and AR-positive, androgen-independent C4-2B prostate cancer cells,
      proteasome inhibition by pristimerin results in suppression of AR protein prior
      to apoptosis. Our data demonstrate, for the first time, that the proteasome is a
      primary target of pristimerin in prostate cancer cells and inhibition of the
      proteasomal chymotrypsin-like activity by pristimerin is responsible for its
      cancer cell death-inducing property.

PMID- 17541981
TI  - Role of phospholipase D2 in anti-apoptotic signaling through increased
      expressions of Bcl-2 and Bcl-xL.
AB  - We have previously reported that Fas-resistant A20 cells (FasR) have
      phospholipase D (PLD) activity upregulated by endogenous PLD2 overexpression. In
      the present study, we investigated how overexpressed PLD2 in FasR could generate
      survival signals by regulating the protein levels of anti-apoptotic Bcl-2 and Bcl
      xL. To confirm the effect of PLD2 on Bcl-2 protein levels, we transfected PLD2
      into wild-type murine B lymphoma A20 cells. The transfected cells showed markedly
      the increases in Bcl-2 and Bcl-xL protein levels, and became resistant to Fas
      induced apoptosis, similar to FasR. Treatment of wild-type A20 cells with
      phosphatidic acid (PA), the metabolic end product of PLD2 derived from
      phosphatidylcholin, markedly increased levels of anti-apoptotic Bcl-2 and Bcl-xL
      proteins. Moreover, PA-induced expressions of Bcl-2 and Bcl-xL were enhanced by
      propranolol, an inhibitor of PA phospholydrolase (PAP), whereas completely
      blocked by mepacrine, an inhibitor of phospholipase A(2) (PLA(2)), suggesting
      that PLA(2) metabolite of PA is responsible for the increases in Bcl-2 and Bcl-xL
      protein levels. We further confirmed the involvement of arachidonic acid (AA) in
      PA-induced survival signals by showing that 1,2-dipalmitoyl-sn-glycero-3
      phosphate (DPPA), PA without AA, was unable to increase Bcl-2 and Bcl-xL
      proteins. Moreover, PA notably increased cyclooxygenase (COX)-2 protein
      expression, and PA-induced expression of both Bcl-2 and Bcl-xL was inhibited by
      NS-398, a specific inhibitor of COX-2. Taken together, these findings demonstrate
      that PA generated by PLD2 plays an important role in cell survival during Fas
      mediated apoptosis through the increased Bcl-2 and Bcl-xL protein levels which
      resulted from PLA(2) and AA-COX2 pathway.

PMID- 17541982
TI  - Cancer stem cells in leukemia, recent advances.
AB  - The history of stem cell research was started in the early 1900s in Europe where
      the researcher realized that various types of blood cells came from a particular
      "stem cells." However, it was not until 1963 that the first quantitative
      description of the self-renewal activities of transplanted mouse bone marrow
      cells were documented by Canadian scientist Ernest A McCulloch and James E Till
      in Toronto. The concept of cancer stem cells has been used over 50 years ago;
      whereas the strong evidence for the existence of a Cancer Stem Cells was obtained
      recently. Consequently, there is increasing attention in recent year about cancer
      stem cells. The findings from recent studies support the concept that stem cells
      are integral to the development of several forms of human cancer. Changes in stem
      cell behavior can contribute to tumor formation. Leukemia is a cancer of blood
      forming tissue, including the bone marrow and lymphatic system. Leukemic stem
      cells represent the cancer stem cells in the leukemia. In this review, we
      summarize the recent advance in the study of leukemic stem cells.

PMID- 17541983
TI  - Pulmonary lymphangioleiomyomatosis (LAM): progress and current challenges.
AB  - Lymphangioleiomyomatosis (LAM), a rare lung disease, is characterized by the
      progressive proliferation, migration, and differentiation of smooth muscle (SM)
      like LAM cells, which lead to the cystic destruction of the lung parenchyma,
      obstruction of airways and lymphatics, and loss of pulmonary function. LAM is a
      disease predominantly affecting women and is exacerbated by pregnancy; only a
      lung transplant can save the life of a patient. It has been discovered that in
      LAM, somatic or genetic mutations of tumor suppressor genes tuberous sclerosis
      complex 1 (TSC1) or TSC2 occur and the TSC1/TSC2 protein complex functions as a
      negative regulator of the mTOR/S6K1 signaling pathway. These two pivotal
      observations paved the way for the first rapamycin clinical trial for LAM. The
      recent discoveries that TSC1/TSC2 complex functions as an integrator of signaling
      networks regulated by growth factors, insulin, nutrients, and energy heightened
      the interest regarding this rare disease because the elucidation of disease
      relevant mechanisms of LAM will promote a better understanding of other metabolic
      diseases such as diabetes, cancer, and cardiovascular diseases. In this review,
      we will summarize the progress made in our understanding of TSC1/TSC2 cellular
      signaling and the molecular mechanisms of LAM; we will also highlight some of the
      lesser explored directions and challenges in LAM research.

PMID- 17541984
TI  - Possible association of the pro-melanin-concentrating hormone gene with a greater
      body mass index as a side effect of the antipsychotic olanzapine.
AB  - Following our report of a linkage at 12q24 with a phenotype of obesity under
      antipsychotics, we tested the pro-melanin-concentrating hormone (PMCH) candidate
      gene for a possible association in humans with the body mass index (BMI; kg/m2)
      in unrelated schizophrenic patients (SZ) receiving antipsychotics (N = 300) and
      in controls (CTL; N = 150). Subjects were classified in obese (OB) (BMI > or = 30
      kg/m2), overweight (25 < or = BMI < 30 kg/m2), and normal weight (BMI < 25 kg/m2)
      groups. Single nucleotide polymorphisms (SNP) rs7973796 and rs11111201, located
      5' at -4.5 kb and 3' at +1.8 kb, respectively, of PMCH were genotyped.
      Interaction effects of genotypes and antipsychotic treatment on BMI were tested
      in a covariance analysis with age and gender as covariates. Interaction effects
      on the prevalence of obesity were tested in a logistic regression analysis. For
      subjects under 50 years, the effect of the rs7973796 genotype on BMI differed
      between the SZ patients taking olanzapine and CTL group (interaction P = 0.025).
      Olanzapine-treated SZ patients carrying the ancestral homozygote genotype showed
      a higher BMI for rs7973796 (P = 0.016 with the LSMeans t-test) than the variant
      homozygotes. Accordingly, the ORs for obesity associated with rs7973796 genotypes
      differed in the SZ patients taking olanzapine compared to the CTL group
      (interaction P = 0.0094). The G allele was associated with an increase in the
      odds of obesity in SZ patients taking olanzapine. No association was observed for
      those over 50 years, or for rs11111201. These results suggest that the common
      allele of PMCH rs7973796 may be associated with a greater BMI in olanzapine
      treated SZ patients.

PMID- 17541985
TI  - Uptake behavior of embryonic chick liver cells.
AB  - The capacity of selective uptake by liver cells, focusing particularly on the
      parenchymal and perisinusoidal stellate cells during chick liver development (8
      18 days of incubation), was ultrastructurally examined after injection of 240-nm
      diameter lecithin (phosphatidylcholine) -coated or noncoated beads into the
      extraembryonic circulation. Cytoplasmic projections of both cells as well as
      extrasinusoidal macrophages reached into the sinusoid-like vascular spaces. The
      primitive perisinusoidal stellate cells were identified by immunocytochemistry as
      being rich in desmin-positive cytoplasmic intermediate filaments. The cells
      demonstrated selective uptake of noncoated beads by means of their cytoplasmic
      projections. These findings were significant in the early period of incubation,
      indicating that the phagocytic activity is a characteristic and transient
      phenomenon of developmental differentiation. Large numbers of coated and a few
      noncoated beads penetrated into the perivascular spaces. The parenchymal cells
      incorporated only the coated beads that passed through the endothelial lining,
      suggesting that these cells express selective but limited phagocytic capacity
      against large "foreign" substances even long before their maturation. The cell
      projections were not engaged in uptake function. Extrasinusoidal macrophages,
      Kupffer cells, and intraluminal primitive macrophages all took up both beads;
      however, lecithin coating of the beads clearly suppressed their uptake function.
      These data suggest that the uptake function of large "foreign" substances appears
      to be intrinsic to liver cells and lecithin coating would be useful for
      delivering large substances to parenchymal cells.

PMID- 17541986
TI  - Comparison of different methods of risk stratification in urgent and emergency
      surgery.
AB  - BACKGROUND: The aim was to compare a number of risk scoring systems prospectively
      in a cohort of patients who underwent non-elective surgery. METHODS: This was a
      cohort study of 2349 consecutive patients who had urgent or emergency surgery in
      a district general hospital in the UK. All patients were scored prospectively
      using the Revised Goldman Cardiac Risk Index (RGCRI), Portsmouth modification of
      the Physiological and Operative Severity Score for the enUmeration of Mortality
      and morbidity (P-POSSUM), Surgical Risk Score (SRS) and Biochemistry and
      Haematology Outcome Models (BHOM). Actual 30-day and 1-year survival rates were
      compared with the predicted outcomes using receiver-operator characteristic (ROC)
      curves and Hosmer-Lemeshow analysis. RESULTS: Some 141 patients (6.0 per cent)
      died within 30 days of operation. This increased to 254 (10.8 per cent) by 1
      year. The area under the ROC curve for death within 30 days was 0.90 for P
      POSSUM, 0.85 for SRS, 0.84 for BHOM and 0.73 for RGCRI. Only the first three risk
      scores were able to discriminate accurately within the groups (area under ROC
      curve over 0.8), with no significant variation between expected and observed
      mortality rates confirmed by Hosmer-Lemeshow analysis. Similar results were found
      for the ability of each score to predict outcome at 1 year. CONCLUSION: P-POSSUM,
      SRS and BHOM scoring systems were all able to predict outcome after emergency and
      urgent surgery, but the SRS had the advantage of ease of calculation. BHOM
      requires only the most commonly available blood test data and the computer
      holding these data can easily perform the calculation.

PMID- 17541987
TI  - Tumour cell dissemination following endoscopic stent insertion.
AB  - BACKGROUND: This study examined whether colonoscopy or endoscopic stent insertion
      increases levels of carcinoembryonic antigen (CEA) and/or cytokeratin (CK) 20
      mRNA expression in the peripheral circulation of patients with colorectal cancer.
      METHODS: Peripheral venous blood samples were obtained before and after
      colonoscopy (38 patients) or colonic stent insertion (20). Twenty patients
      undergoing colonoscopy for benign conditions served as controls. Expression of
      mRNA was quantified using real-time reverse transcriptase-polymerase chain
      reaction. RESULTS: Circulating CK20 mRNA was detected in 13 of 38 patients who
      had a colonoscopy and eight of 20 patients with stent insertion. CK20 mRNA
      expression was increased following stent insertion (P = 0.007) but not after
      staging colonoscopy (P = 0.454). CEA mRNA was detected in one patient who had
      colonoscopy and two who had a stent inserted. Neither CEA nor CK20 mRNA was found
      in blood samples from controls. CONCLUSION: Endoscopic insertion of colonic
      stents but not staging colonoscopy results in increased levels of CK20 mRNA in
      the peripheral circulation.

PMID- 17541988
TI  - Magnetic resonance at or below the earth's magnetic field.

PMID- 17541989
TI  - Lipid and fatty acid composition of diatoms revisited: rapid wound-activated
      change of food quality parameters influences herbivorous copepod reproductive
      success.
AB  - Lipid and fatty acid composition are considered to be key parameters that
      determine the nutritive quality of phytoplankton diets for zooplanktonic
      herbivores. The fitness, reproduction and physiology of the grazers are
      influenced by these factors. The trophic transfer of lipids and fatty acids from
      algal cells has been typically studied by using simple extraction and
      quantification approaches, which, as we argue here, do not reflect the actual
      situation in the plankton. We show that cell disruption, as it occurs during a
      predator's grazing on diatoms can drastically change the lipid and fatty acid
      content of the food. In some algae, a rapid depletion of polyunsaturated fatty
      acids (PUFAs) is observed within the first minutes after cell disruption. This
      fatty acid depletion is directly linked to the production of PUFA-derived
      polyunsaturated aldehydes (PUA); these are molecules that are thought to be
      involved in the chemical defence of the algae. PUA-releasing diatoms are even
      capable of transforming lipids from other sources if these are available in the
      vicinity of the wounded cells. Fluorescent staining reveals that the enzymes
      involved in lipid transformation are active in the foregut of copepods, and
      therefore link the depletion processes directly to food uptake. Incubation
      experiments with the calanoid copepod Temora longicornis showed that PUFA
      depletion in PUA-producing diatoms is correlated to reduced hatching success, and
      can be compensated for by externally added single fatty acids.

PMID- 17541990
TI  - Are MAP kinases drug targets? Yes, but difficult ones.
AB  - Pharmaceutical companies are facing an increasing interest in new target
      identification and validation. In particular, extensive efforts are being made in
      the field of protein kinase inhibitors research and development, and the past ten
      years of effort in this field have altered our perception of the potential of
      kinases as drug targets. Therefore, in the drug discovery process, the selection
      of relevant, susceptible protein kinase targets combined with searches for leads
      and candidates have become a crucial approach. The success of recent launches of
      protein kinase inhibitors (Gleevec, Imatinib, Sutent, Iressa, Nexavar, Sprycel)
      gave another push to this field. Numerous other kinase inhibitors are currently
      undergoing clinical trials or clinical development. Some questions are
      nevertheless unanswered, mostly related to the great number of known kinases in
      the human genome, to their similarity with each other, to the existence of
      functionally redundant kinases for specific pathways, and also because the
      connection between particular pathways and diseases is not always clear. The
      review is leading the reader through a panoramic view of protein kinase
      inhibition with a major focus on MAPK, successful examples and clinical
      candidates.

PMID- 17541991
TI  - Fragment-based synthesis and SAR of modified FKBP ligands: influence of different
      linking on binding affinity.
AB  - The viability of the fragment-based approach for lead discovery depends on
      reliable fragment-screening methods combined with straightforward fragment
      linking- or fragment-growing-chemistry. In the present study we sought a flexible
      synthetic approach that would allow efficient synthesis of a variety of linkers
      that can subsequently be tested for biological activity. We applied this approach
      to fragments known to bind to FKBP12 (FK506 binding protein), a peptidyl-prolyl
      isomerase involved in immunosuppression and neural functioning. In our set of
      linked FKBP ligands, ester and thioester linkages resulted in high-affinity
      ligands, whereas an amide linkage decreased affinity remarkably; oxime and
      triazole linkages were not tolerated by the target protein's binding pocket,
      rendering these ligands ineffective. By investigating corresponding derivatized
      non-linked fragments and docking studies of linked fragments, we were able to
      evaluate the effect of the linker region on ligand binding affinity.

PMID- 17541992
TI  - Highly potent and selective substrate analogue factor Xa inhibitors containing D
      homophenylalanine analogues as P3 residue: part 2.
AB  - A series of highly potent substrate-analogue factor Xa inhibitors containing D
      homophenylalanine analogues as the P3 residue has been identified by systematic
      optimization of a previously described inhibitor structure. An initial lead,
      benzylsulfonyl-D-hPhe-Gly-4-amidinobenzylamide (3), inhibits fXa with an
      inhibition constant of 6.0 nM. Most modifications of the P2 amino acid and P4
      benzylsulfonyl group did not improve the affinity and selectivity of the
      compounds as fXa inhibitors. In contrast, further variation at the P3 position
      led to inhibitors with significantly enhanced potency and selectivity. Inhibitor
      27, benzylsulfonyl-D-homo-2-pyridylalanyl(N-oxide)-Gly-4-amidinobenzylamide,
      inhibits fXa with a K(i) value of 0.32 nM. The inhibitor has strong anticoagulant
      activity in plasma and doubles the activated partial thromboplastin time and
      prothrombin time at concentrations of 280 nM and 170 nM, respectively. Compound
      27 inhibits the prothrombinase complex with an IC(50) value of 5 nM and is
      approximately 50 times more potent than the reference inhibitor DX-9065a in this
      assay.

PMID- 17541993
TI  - Oxime and oxime ether derivatives of 1,4-benzothiazine related to oxiconazole.
AB  - The synthesis, in vitro antifungal activity, and molecular docking experiments of
      some oxime and oxime ether derivatives of azole 1,4-benzothiazine are reported
      herein, with the aim of evaluating the influence of a partially constrained
      scaffold that is structurally related to Oxiconazole and bearing the 1,4
      benzothiazine moiety, on the inhibition of Candida albicans CYP51.

PMID- 17541994
TI  - SERS classification of highly related performance enhancers.

PMID- 17541995
TI  - The mechanism of C--X (X=F, Cl, Br, and I) bond activation in CX4 by a stabilized
      dialkylsilylene.
AB  - The potential-energy surfaces for the abstraction and insertion reactions of
      dialkylsilylene with carbon tetrahalides (CX4) have been characterized in detail
      using density functional theory (B3LYP), including zero-point corrections. Four
      CX4 species, CF4, CCl(4), CBr4, and CI(4), were chosen as model reactants. The
      theoretical investigations described herein suggest that of the three possible
      reaction paths, the one-halogen-atom abstraction (X abstraction), the one-CX3
      group abstraction (CX3 abstraction), and the insertion reaction, the X
      abstraction reaction is the most favorable, with a very low activation energy.
      However, the insertion reaction can lead to the thermodynamically stable
      products. Moreover, for a given stable dialkylsilylene, the chemical reactivity
      has been found to increase in the order CF4<<CCl(4)<CBr4<CI(4), that is, the
      heavier the halogen atom (X), the more facile is its reaction with a stable
      dialkylsilylene. In particular, halogen abstraction is always predicted to be
      much more favorable than abstraction of a CX3 group from both energetic and
      kinetic viewpoints. In brief, electronic as well as steric factors play a crucial
      role in determining the chemical reactivity of the haloalkane species,
      kinetically as well as thermodynamically. Our conclusions based on the results of
      our theoretical investigations are in accordance with available experimental
      observations. Furthermore, a configuration-mixing model based on the work of
      Pross and Shaik has been used to rationalize the computational results. The
      results obtained allow a number of predictions to be made.

PMID- 17541996
TI  - Evidence for a SN2-type pathway for phosphine exchange in phosphine-phosphenium
      cations, [R2P--PR'3]+.
AB  - Abstraction of a Cl(-) ion from the P-chlorophospholes, R4C4PCl (R=Me, Et),
      produced the P--P bonded cations [R4C4P--P(Cl)C4R4]+, which reacted with PPh3 to
      afford X-ray crystallographically characterised phosphine-phosphenium cations
      [R4C4P(PPh3)]+ (R=Me, Et). Examination of the 31P-{1H} NMR spectrum of a solution
      (CH2Cl(2)) of [Et4C4P-(PPh3)]+ and PPh3 revealed broadening of the resonances due
      to both free and coordinated PPh3, and importantly it proved possible to measure
      the rate of exchange between PPh3 and [Et4C4P-(PPh3)]+ by line shape analysis
      (gNMR programmes). The results established second-order kinetics with DeltaS( not
      equal)=(-106.3+/-6.7) J mol(-1) K(-1), DeltaH( not equal)=(14.9+/-1.6) kJ mol(-1)
      and DeltaG( not equal) (298.15 K)=(46.6+/-2.6) kJ mol(-1), values consistent with
      a SN2-type pathway for the exchange process. This result contrasts with the
      dominant dissociative (S(N)1-type) pathway reported for the analogous exchange
      reactions of the [ArNCH2CH2N(Ar)P(PMe3)]+ ion, and to understand in more detail
      the factors controlling these two different reaction pathways, we have analysed
      the potential energy surfaces using density functional theory (DFT). The
      calculations reveal that, whilst phosphine exchange in [Et4C4P(PPh3)]+ and
      [ArNCH2CH2N(Ar)P(PMe3)](+) is superficially similar, the two cations differ
      significantly in both their electronic and steric requirements. The high
      electrophilicity of the phosphorus center in [Et4C4P]+, combined with strong pi
      pi interactions between the ring and the incoming and outgoing phenyl groups of
      PPh3, favours the SN2-type over the SN1-type pathway in [Et4C4P(PPh3)]+.
      Effective pi-donation from the amide groups reduces the intrinsic
      electrophilicity of [ArNCH2CH2N(Ar)P]+, which, when combined with the steric bulk
      of the aryl groups, shifts the mechanism in favour of a dissociative SN1-type
      pathway.

PMID- 17541997
TI  - Using relative distributions to investigate the body mass index in England and
      Canada.
AB  - In this paper we use relative distributions to examine changes in the
      distribution of the body mass index (BMI) in England and Canada during the period
      1994/5-2000/1. The use of relative distributions allows us to describe changes in
      the whole distribution of the BMI in a non-parametric fashion. While statistics
      analogous to the Gini index can be constructed based on the relative
      distribution, important characteristics of changes in the distribution of the BMI
      such as changes in the proportions overweight and obese are more naturally
      handled using measures of relative polarization. Our results show that while BMI
      has increased in both countries, BMI in England has increased at a much faster
      rate than in Canada. Both groups show polarization over time towards both tails
      of the weight distribution, with the English polarizing towards the upper tail at
      a faster rate than Canadians.

PMID- 17541998
TI  - The role of corticosteroids in muscular dystrophy: a critical appraisal.
AB  - Over the years various steroid trials have been conducted in Duchenne muscular
      dystrophy (DMD). In children who are still able to walk as well as in those who
      are wheelchair-bound, corticosteroids have been found to stabilize muscle
      strength for a period of time. Controlled clinical observations have shown that
      some boys remain ambulatory for years longer than reported in natural history
      data. The two main steroids used are prednisone/prednisolone and deflazacort.
      They are probably equally effective in stabilizing muscle strength but may have
      different side-effect profiles; for instance, deflazacort causes less weight
      gain. The exact mechanism by which steroids slow the dystrophic process is under
      investigation. DMD children treated long term also seem to develop other
      complications of the condition less frequently. For instance, they develop
      respiratory insufficiency later and have fewer cardiac symptoms. The therapeutic
      value of corticosteroids is limited, but these drugs represent the best treatment
      option currently available.

PMID- 17541999
TI  - Acute vibration reduces Abeta nerve fiber sensitivity and alters gene expression
      in the ventral tail nerves of rats.
AB  - Long-term occupational exposure to hand-arm vibration can result in a permanent
      reduction in tactile sensitivity in exposed fingers and hands. Little is known
      about how vibration causes this reduction in sensitivity, and currently no
      testing procedures have been developed to monitor changes in sensory perception
      during ongoing exposures. We used a rat-tail model of hand-arm vibration syndrome
      (HAVS) to determine whether changes in sensory nerve function could be detected
      after acute exposure to vibration. Nerve function was assessed using the current
      perception threshold (CPT) method. We also determined whether changes in nerve
      function were associated with changes in gene transcription. Our results
      demonstrate that the CPT method can be used to assess sensory nerve function
      repeatedly in rats and can detect transient decreases in the sensitivity of Abeta
      nerve fibers caused by acute exposure to vibration. This decrease in Abeta fiber
      sensitivity was associated with a reduction in expression of nitric oxide
      synthase-1, and a modest increase in calcitonin gene-related peptide transcript
      levels in tail nerves 24 h after vibration exposure. These transient changes in
      sensory perception and transcript levels induced by acute vibration exposure may
      be indicators of more prolonged changes in peripheral nerve physiology.

PMID- 17542000
TI  - The value of combined-modality therapy in elderly patients with stage III
      nonsmall cell lung cancer.
AB  - BACKGROUND: The objective of this study was to assess the value of combined
      modality therapy in elderly patients by comparing the differences in outcome
      between patients who received radiotherapy (RT) alone and patients who received
      RT plus chemotherapy for stage III nonsmall cell lung cancer (NSCLC). METHODS:
      The North Central Cancer Treatment Group performed 2 recent Phase III trials for
      stage III NSCLC. The first trial, NCCTG 90-24-51, included 3 arms: once-daily RT
      (QDRT) alone, twice-daily RT (BIDRT) alone, and concurrent chemotherapy plus
      BIDRT. The second trial, NCCTG 94-24-52, included 2 arms and compared concurrent
      chemotherapy with either QDRT or BIDRT. The chemotherapy arms of both trials
      included etoposide and cisplatin administered concurrently with RT. Only the
      patients aged >/=65 years (elderly) who participated in those trials were
      included in this analysis. RESULTS: Of the 166 elderly patients who were included
      in this analysis, 37 patients received RT alone, and 129 patients received
      concurrent chemotherapy plus RT. The median and 5-year survival rates were 10.5
      months and 5.4% for the RT alone group compared with 13.7 months and 14.7% for
      the RT plus chemotherapy group (log-rank P = .05). Patients who received RT plus
      chemotherapy experienced significantly greater severe toxicity (grade >/=3)
      compared with patients who received RT alone (89.9% vs 32.4%; P < 0.01).
      CONCLUSIONS: Elderly patients who participated in these trials appeared to gain a
      survival advantage from RT and chemotherapy compared with RT alone. As is the
      case with younger patients, this benefit came at the cost of additional toxicity.

PMID- 17542001
TI  - On the structure of the inverse kinematics map of a fragment of protein backbone.
AB  - Loop closure in proteins requires computing the values of the inverse kinematics
      (IK) map for a backbone fragment with 2n > or = 6 torsional degrees of freedom
      (dofs). It occurs in a variety of contexts, e.g., structure determination from
      electron-density maps, loop insertion in homology-based structure prediction,
      backbone tweaking for protein energy minimization, and the study of protein
      mobility in folded states. The first part of this paper analyzes the global
      structure of the IK map for a fragment of protein backbone with 6 torsional dofs
      for a slightly idealized kinematic model, called the canonical model. This model,
      which assumes that every two consecutive torsional bonds C(alpha)--C and N-
      C(alpha) are exactly parallel, makes it possible to separately compute the
      inverse orientation map and the inverse position map. The singularities of both
      maps and their images, the critical sets, respectively, decompose SO(3) x R(3)
      into open regions where the number of IK solutions is constant. This
      decomposition leads to a constructive proof of the existence of a region in R(3)
      x SO(3) where the IK of the 6-dof fragment attains its theoretical maximum of 16
      solutions. The second part of this paper extends this analysis to study fragments
      with more than 6 torsional dofs. It describes an efficient recursive algorithm to
      sample IK solutions for such fragments, by identifying the feasible range of each
      successive torsional dof. A numerical homotopy algorithm is then used to deform
      the IK solutions for a canonical fragment into solutions for a noncanonical
      fragment. Computational results for fragments ranging from 8 to 30 dofs are
      presented.

PMID- 17542002
TI  - Parametric latent class joint model for a longitudinal biomarker and recurrent
      events.
AB  - A joint model for a longitudinal biomarker and recurrent events is proposed. This
      general model accommodates the effects of covariates on the biomarker and event
      processes, the effects of accumulating event occurrences, and effects caused by
      interventions after each event occurrence. Association between the biomarker and
      recurrent event processes is captured through a latent class structure, which
      also serves to handle an underlying heterogeneous population. We use the EM
      algorithm for maximum likelihood estimation of the model parameters and a
      penalized likelihood measure to determine the number of latent classes. This
      joint model is validated by simulation and illustrated with a data set from
      epileptic seizure study.

PMID- 17542003
TI  - Bending energetics of tablet-shaped micelles: a novel approach to rationalize
      micellar systems.
AB  - A novel approach to rationalize micellar systems is expounded in which the
      structural behavior of tablet-shaped micelles is theoretically investigated as a
      function of the three bending elasticity constants: spontaneous curvature (H0),
      bending rigidity (k(c)), and saddle-splay constant (k(c)). As a result,
      experimentally accessible micellar properties, such as aggregation number, length
      to-width ratio, and polydispersity, may be related to the different bending
      elasticity constants. It is demonstrated that discrete micelles or connected
      cylinders form when H0 > 1/4xi, where xi is the thickness of a surfactant
      monolayer, whereas various bilayer structures are expected to predominate when H0
      < 1/4xi. Our theory predicts, in agreement with experiments, a transition from
      discrete globular (tablet-shaped) micelles to a phase of ordered, or disordered,
      connected cylinders above a critical surfactant concentration. Moreover, a novel
      explanation for the mechanism of growth, from small globular to long rodlike or
      wormlike micelles, follows as a consequence from the theory. In accordance,
      polydisperse elongated micelles (large length-to-width ratio) form as the bending
      rigidity is lowered, approaching the critical point at k(c) = 0, whereas
      monodisperse globular micelles (small length-to-width ratio) are expected to be
      present at large k(c) values. The spontaneous curvature mainly determines the
      width of tablet-shaped or ribbonlike micelles, or the radius of disklike
      micelles, whereas the saddle-splay constant primarily influences the size but not
      the shape of the micelles.

PMID- 17542004
TI  - Preparation and characterization of hydroxyapatite/poly(ethylene glutarate)
      biomaterials.
AB  - Hydroxyapatite/poly(ethylene glutarate) (HAp/PEG) biomaterial composites were
      prepared by ring-opening polymerization (ROP) of cyclic oligo(ethylene glutarate)
      (C-PEG) in porous HAp scaffolds. The HAp/C-PEG precomposites were prepared by
      immersing the porous HAp scaffolds in the mixture solution of C-PEG and dibutyl
      tinoxide catalyst overnight and polymerizing at 200 degrees C for 24, 48, and 72
      h under vacuum. The successful ROP of C-PEG in the porous HAp scaffolds was
      corroborated by the signals of hydroxyl end-group of PEG shown in the (1)H NMR
      spectrum of the ROP-products extracted from the composites. PEG in the composites
      was present as a thin layer coating on the HAp grains and was evenly distributed
      throughout the samples. The PEG content was about 13-16 wt % and decreased with
      increasing polymerization time. Its molecular weight (M(w), weight average)
      measured by gel permeation chromatography was in the range of 4300-6800 g/mol.
      Compressive strength of the HAp/PEG composites was significantly increased from 3
      MPa of the porous HAp scaffold to 11-15 MPa, depending on the PEG content in the
      composites. In vitro bioactivity of the HAp/PEG composites was studied by soaking
      in simulated body fluid (SBF) at 36.5 degrees C for 7-28 days. After prolonged
      soaking, the HAp nanocrystals precipitated from the SBF solution and formed as a
      layer of globular aggregates, coated on the composite surfaces. This result
      suggested that the HAp/PEG composite was a bioactive material.

PMID- 17542005
TI  - Parental narratives on genetic testing for children with hearing loss: a
      qualitative inquiry.
AB  - Studies on parental attitudes towards genetic testing for hearing loss have
      surveyed parents of newborns with hearing loss as well as deaf and hearing
      adults. Although research indicates that most people have positive attitudes
      about genetic testing, few studies examine parental narratives about the personal
      implications of genetic hearing loss in their children. In this qualitative study
      we conducted semi-structured interviews with 24 parents whose children had been
      referred for, but had not yet undergone, genetic testing for hearing loss. The
      parents were recruited to represent a diverse range of racial, ethnic, and
      socioeconomic groups. Genetics and genetic testing for hearing loss were poorly
      understood topics. Beyond supporting or opposing genetic testing for hearing
      loss, parents' construction of meaning included struggles to locate
      responsibility (metaphysical attributions, ascription or alleviation of parental
      responsibility) as well as questions about the usefulness and implications of
      genetic testing for hearing loss in their child. Based on the themes that emerged
      from this study, we highlight the need for healthcare professionals to be aware
      and sensitized to parents' narratives, personal meanings and socio-cultural
      context when referring them for genetic testing for hearing loss. Listening
      attentively to parental narratives can help minimize prevailing misconceptions
      among parents and enable appropriate medical care and education.

PMID- 17542006
TI  - Assessing parental attitudes toward genetic testing for childhood hearing loss:
      before and after genetic consultation.
AB  - We report on the development of a Genetic Attitude Assessment Tool (GAAT) to
      measure parental attitudes in contemplating genetic testing for childhood hearing
      loss, and to examine the differences in assessments made before and after genetic
      counseling. The GAAT tool was administered to a convenient sample of 119 parents
      of children with bilateral sensorineural hearing loss. The respondents completed
      the survey either before (n = 77) or after (n = 42) genetic counseling.
      Exploratory Factor Analysis was applied to identify and quantify the underlying
      psychosocial structure. Our results showed the validated 54-item GAAT instrument
      contains six subscales: (1) "test intention," (2) "beliefs in non-genetic causes
      of hearing loss," (3) "deferral of decision to undergo genetic testing," (4)
      "appropriate use of genetic testing results," (5) "beliefs in the benefits," and
      (6) "concerns about stigma." The respondents who answered the survey after
      genetic counseling had higher "test intention" (P = 0.017) and endorsed to a
      greater extent "beliefs in the benefits" (P < 0.001). They believed to a lesser
      extent that childhood hearing loss was due to "non-genetic causes" (P < 0.001)
      and were less inclined to prefer "decision deferral" (P = 0.031). Respondents who
      themselves had a hearing loss expressed a significantly weaker belief in "non
      genetic causes" of hearing loss (P < 0.0001). In conclusion the validated GAAT
      instrument is responsive to changes in parental attitudes after genetic
      counseling. The GAAT may be used to monitor parental attitudes serially, to
      further understand how parental attitudes change from pre genetic counseling,
      post genetic counseling, to post test result disclosure.

PMID- 17542007
TI  - A case for genetics education: collaborating with speech-language pathologists
      and audiologists.
AB  - Because speech-language pathologists (SLPs) and audiologists (AUDs) are among the
      first referrals for parents of children exhibiting feeding, speech, language,
      hearing, and balance difficulties, it is important for SLP and AUD professionals
      to recognize genetic causes of and contributions to complex and Mendelian
      communication disorders. We review genetics in the curricula of speech-language
      pathology and audiology programs and obstacles to its integration throughout
      curricula. We present suggestions about how SLPs and AUDs can aid in diagnosis
      and contribute their clinical expertise in characterizing phenotypes, followed
      with a review of a new genetics-education website developed by the National
      Coalition for Health Professional Education in Genetics (NCHPEG), the University
      of Cincinnati, and the National Society of Genetic Counselors. The need to
      integrate genetics content into curricula and continuing education across
      disciplines is clear, as is the need for and benefit of multidisciplinary
      collaboration in patient care. The NCHPEG site for speech-language pathology and
      audiology begins to address those needs and may serve as a practical model for
      future multidisciplinary collaborations between genetics professionals and other
      health professions.

PMID- 17542008
TI  - Preliminary study of the safety and efficacy of donepezil hydrochloride in
      children with Down syndrome: a clinical report series.
AB  - There is growing evidence to support the use of early central cholinergic
      enhancement to improve cognitive functioning in individuals with Down syndrome
      (DS). This report summarizes preliminary safety and cognitive efficacy data for
      seven children (8-13 years) with DS who participated in a 22-week, open-label
      trial of donepezil hydrochloride. Donepezil was dosed once daily at 2.5 mg and,
      based on tolerability, increased to 5 mg/day. Safety assessments were conducted
      at Week 1 (baseline), Week 8 (2.5 mg donepezil), Week 16 (5 mg) and Week 22
      (after the donepezil had been discontinued). Measures of cognitive function were
      administered at each visit, encompassing the following domains: memory;
      attention; mood; and adaptive functioning. Donepezil was well tolerated at the
      2.5 and 5 mg doses. The side effects were mild, transient, and consistent with
      the adverse events noted with cholinesterase inhibitors. Some children showed
      improvement on measures of memory (NEPSY Memory for Names and Narrative Memory)
      and sustained attention to tasks (Conners' Parent Rating Scales), although
      increased irritability and/or assertiveness were noted in some patients. Overall,
      this clinical report series adds to our initial findings of language gains in
      children with DS treated with donepezil. It also supports the need for larger,
      double-blind studies of the safety and efficacy of donepezil and other
      cholinesterase inhibitors for children with DS.

PMID- 17542009
TI  - Characterization of deltoid, a chimeric protein containing the oligomerization
      site of hepatitis delta antigen.
AB  - Both forms of the hepatitis delta antigen (HDAg) encoded by hepatitis delta virus
      are active only as oligomers. Previous studies showed that quadrin, a synthetic
      50-residue peptide containing residues 12-60 from the N-terminus of HDAg,
      interferes with HDAg oligomerization, forms an alpha-helical coiled coil in
      solution, and forms a novel square octamer in the crystal consisting of four
      antiparallel coiled-coil dimers joined at the corners by hydrophobic binding of
      oligomerization sites located at each end of the dimers. We designed and
      synthesized deltoid (CH3CO-[Cys23]HDAg-(12-27)-seryl-tRNA synthetae-(59-65)
      [Cys42]HDAg-(34-60)-Tyr-NH2), a chimeric protein that structurally resembles one
      end of the quadrin dimer and contains a single oligomerization site. The 51
      residue chain of deltoid contains a seven-residue alpha-hairpin loop in place of
      the remainder of the quadrin dimer plus Cys12 and Cys31 for forming an intrachain
      disulfide bridge. Reduced, unbridged deltoid (Tm=61 degrees C, DeltaG(H2O)=-1.7
      kcal mol(-1)) was less stable to denaturation by heat or guanidine HCl than
      oxidized, intrachain disulfide-bridged deltoid (Tm>80 degrees C, DeltaG(H2O)=-2.6
      kcal mol(-1)). Each form is an alpha-helical dimer that reversibly dissociates
      into two monomers (Kd=80 microM).

PMID- 17542010
TI  - Kinetics of the helix/coil transition of the collagen-like peptide (Pro-Hyp
      Gly)10.
AB  - This article measures the rates of folding and unfolding of the collagen-like
      peptide (Pro-Hyp-Gly)(10) over overlapping concentration and temperature ranges.
      The data allow calculation of the orders of the folding and the unfolding
      reactions, the effective Arrhenius activation energies, and numerical solution of
      the differential equation controlling the helix/coil transition during
      temperature scanning. The resulting predictions of helicity closely followed DSC
      measurements of the peptide in both up- and down-scanning modes, confirming the
      validity of the theoretical equations governing the kinetics of the
      folding/unfolding process. In both up- and down-scanning, three regions were
      apparent: "quasistatic," "rate," and "mixed." At very low scanning rates, a
      quasistatic region revealed a broad, short endotherm that was independent of
      scanning rate, but dependent on concentration and equal to the equilibrium
      endotherm. At high up-scanning rates, the "rate region" endotherm was sharp and
      tall and T(max) increased with scanning rate. In down-scanning, the "rate peak"
      was very broad and very short and T(max) decreased with scanning rate. The "mixed
      region" showed nascent "rate" and nascent "quasistatic" peaks, which were evident
      in the same up-scan under certain conditions. Comparison of (Pro-Hyp-Gly)(10) and
      (Pro-Pro-Gly)(10) showed that the higher temperature stability of (Pro-Hyp
      Gly)(10) is due mainly to its slower rate of unfolding and higher activation
      energy.

PMID- 17542011
TI  - Clinical diagnostic criteria for dementia associated with Parkinson's disease.
AB  - Dementia has been increasingly more recognized to be a common feature in patients
      with Parkinson's disease (PD), especially in old age. Specific criteria for the
      clinical diagnosis of dementia associated with PD (PD-D), however, have been
      lacking. A Task Force, organized by the Movement Disorder Study, was charged with
      the development of clinical diagnostic criteria for PD-D. The Task Force members
      were assigned to sub-committees and performed a systematic review of the
      literature, based on pre-defined selection criteria, in order to identify the
      epidemiological, clinical, auxillary, and pathological features of PD-D. Clinical
      diagnostic criteria were then developed based on these findings and group
      consensus. The incidence of dementia in PD is increased up to six times, point
      prevelance is close to 30%, older age and akinetic-rigid form are associated with
      higher risk. PD-D is characterized by impairment in attention, memory, executive
      and visuo-spatial functions, behavioral symptoms such as affective changes,
      hallucinations, and apathy are frequent. There are no specific ancillary
      investigations for the diagnosis; the main pathological correlate is Lewy body
      type degeneration in cerebral cortex and limbic structures. Based on the
      characteristic features associated with this condition, clinical diagnostic
      criteria for probable and possible PD-D are proposed.

PMID- 17542012
TI  - Genome-level analysis of genetic regulation of liver gene expression networks.
AB  - The liver is the primary site for the metabolism of nutrients, drugs, and
      chemical agents. Although metabolic pathways are complex and tightly regulated,
      genetic variation among individuals, reflected in variations in gene expression
      levels, introduces complexity into research on liver disease. This study
      dissected genetic networks that control liver gene expression through the
      combination of large-scale quantitative mRNA expression analysis with genetic
      mapping in a reference population of BXD recombinant inbred mouse strains for
      which extensive single-nucleotide polymorphism, haplotype, and phenotypic data
      are publicly available. We profiled gene expression in livers of naive mice of
      both sexes from C57BL/6J, DBA/2J, B6D2F1, and 37 BXD strains using Agilent
      oligonucleotide microarrays. These data were used to map quantitative trait loci
      (QTLs) responsible for variations in the expression of about 19,000 transcripts.
      We identified polymorphic local and distant QTLs, including several loci that
      control the expression of large numbers of genes in liver, by comparing the
      physical transcript position with the location of the controlling QTL.
      CONCLUSION: The data are available through a public web-based resource
      (www.genenetwork.org) that allows custom data mining, identification of
      coregulated transcripts and correlated phenotypes, cross-tissue, and cross
      species comparisons, as well as testing of a broad array of hypotheses.

PMID- 17542013
TI  - Decreased drug penetration in inflamed tissue related to changed mucosal
      metabolism in experimental colitis.
AB  - Pathophysiologic changes in mucosal protein expression inflammatory bowel disease
      (IBD) may affect drug concentration in mucosal tissue making it highly relevant
      to drug dose at the site of action and subsequently for success of the therapy.
      Tissue samples from an experimental colitis rat model were mounted in Ussing
      chambers and intratissue concentrations of diverse compounds were quantified.
      Studies with healthy versus colitis tissue samples and respective microsomal
      fractions made it possible to assess the involvement of P-glycoprotein (P-gp) and
      cytochrome P450 3A (CYP3A) on tissue penetration behavior. P-gp-related efflux
      was slightly increased for colitis tissue. Metabolism studies exhibited higher
      tacrolimus and testosterone mucosal metabolism in inflamed tissue. However,
      similar metabolic activity was observed for healthy and colitis groups with
      equivalent CYP3A expression levels in respective microsome fractions. Severity of
      colitis as determined by myeloperoxidase activity was found to have linear
      correlation to changes in tacrolimus degradation (R2 = 0.8299). It is
      hypothesized that increased drug metabolism is dependent on the number of cells
      infiltrating inflamed tissue. A dominant contribution of immune-related cells to
      observed variations in mucosal drug metabolism has been determined. This observed
      pathophysiologic mechanism may have a significant influence on available drug
      concentrations at the inflammation site, thus modifying anti-inflammatory
      efficiency of the therapy.

PMID- 17542014
TI  - Sex-role reversal is reflected in the brain of African black coucals (Centropus
      grillii).
AB  - In most bird species males compete over access to females and have elevated
      circulating androgen levels when they establish and defend a breeding territory
      or guard a mate. Testosterone is involved in the regulation of territorial
      aggression and sexual display in males. In few bird species the traditional sex
      roles are reversed and females are highly aggressive and compete over access to
      males. Such species represent excellent models to study the hormonal modulation
      of aggressive behavior in females. Plasma sex steroid concentrations in sex-role
      reversed species follow the patterns of birds with "traditional" sex-roles. The
      neural mechanisms modulating endocrine secretion and hormone-behavior
      interactions in sex-role reversed birds are currently unknown. We investigated
      the sex differences in the mRNA expression of androgen receptors, estrogen
      receptor alpha, and aromatase in two brain nuclei involved in reproductive and
      aggressive behavior in the black coucal, the nucleus taeniae and the bed nucleus
      of the stria terminalis. In the bed nucleus there were no sex differences in the
      receptor or aromatase expression. In the nucleus taeniae, however, we show for
      the first time, that females have a higher mRNA expression of androgen receptors
      than males. These results suggest that the expression of agonistic and courtship
      behavior in females does not depend on elevated blood hormone levels, but may be
      regulated via increased steroid hormone sensitivity in particular target areas in
      the brain. Hence, aggression in females and males may indeed be modulated by the
      same hormones, but regulated at different levels of the neuroendocrine cascade.

PMID- 17542015
TI  - Roles of glutamate and GABA receptors in setting the developmental timing of
      spontaneous synchronized activity in the developing mouse cortex.
AB  - Spontaneous, synchronized electrical activity (SSA) plays important roles in
      nervous system development, but it is not clear what causes it to start and stop
      at the appropriate times. In previous work, we showed that when SSA in neonatal
      mouse cortex is blocked by TTX in cultured slices during its normal time of
      occurrence (E17-P3), it fails to stop at P3 as it does in control cultured
      slices, but instead persists through at least P10. This indicates that SSA is
      self-extinguishing. Here we use whole-cell recordings and [Ca2+]i imaging to
      compare control and TTX-treated slices to isolate the factors that normally
      extinguish SSA on schedule. In TTX-treated slices, SSA bursts average 4 s in
      duration, and have two components. The first, lasting about 1 s, is mediated by
      AMPA receptors; the second, which extends the burst to 4 s and is responsible for
      most of the action potential generation during the burst, is mediated by NMDA
      receptors. In later stage (P5-P9) control slices, after SSA has declined to about
      4% of its peak frequency, bursts lack this long NMDA component. Blocking this
      NMDA component in P5-P9 TTX-treated slices reduces SSA frequency, but not to the
      low values found in control slices, implying that additional factors help
      extinguish SSA. GABA(A) inhibitors restore SSA in control slices, indicating that
      the emergence of GABA(A)-mediated inhibition is another major factor that helps
      terminate SSA.

PMID- 17542016
TI  - Investigation of human pharmacoscintigraphic behavior of two tablets and a
      capsule formulation of a high dose, poorly water soluble/highly permeable drug
      (efavirenz).
AB  - Human pharmacoscintigraphic behavior of two tablets and a capsule formulation of
      a high dose, poorly water soluble, highly permeable, micronized drug (efavirenz)
      was investigated. The tablets and capsule, prepared with samarium oxide and
      neutron activated to produce radioactive samarium-153, were evaluated for their
      in vivo disintegration and gastrointestinal (GI) transit in healthy subjects
      under fasted condition. Scintigraphic images were acquired to coincide with blood
      sampling times to assess the plasma concentration-time profile in relation to in
      vivo disintegration and GI transit. The mean gastric emptying times were
      approximately the same for all three formulations. Although in vivo dosage form
      disintegration was faster for Tablet A as compared to Tablet B and was similar
      between Tablet A and the capsule, Tablet A showed a slower rate and extent of
      drug absorption than Tablet B and the capsule. The results of this study
      eliminated the initial hypothesis that the difference in in vivo performance
      between the two tablet formulations is due to a different rate of in vivo
      disintegration and suggest that for this drug the in vivo dissolution rate of the
      drug from its disintegrated dosage form was a more important factor affecting the
      rate and extent of drug absorption.

PMID- 17542017
TI  - High pressure differential scanning calorimetry investigations on the pressure
      dependence of the melting of paracetamol Polymorphs I and II.
AB  - A high pressure differential scanning calorimeter (HP-DSC) has been used to
      investigate the pressure dependence of the melting of the monoclinic (Form I) and
      orthorhombic (Form II) polymorphs of paracetamol (acetaminophen). DSC scans
      obtained at ambient pressure show that the stable monoclinic form melts at 442 K
      while the metastable orthorhombic form melts at 430 K. HP-DSC scans obtained for
      pressures up to about 450 MPa show that the melting temperatures of both Forms I
      and II increase with increasing pressure, but the latter more rapidly than the
      former. This results in a cross-over at about 250 MPa, where the two forms have
      approximately the same melting temperature, while at higher pressures Form II
      becomes the more stable phase. Although no solid-solid transitions have been
      observed, the coordinates of the I-II-liquid triple point have been found
      experimentally (p = 258.7 MPa and T = 489.6 K) for the first time, and confirm
      those predicted by Espeau et al. from a topological p-T diagram based on
      theoretical arguments and experimental data at ambient pressure.

PMID- 17542018
TI  - Grapefruit juice-drug interactions: Grapefruit juice and its components inhibit P
      glycoprotein (ABCB1) mediated transport of talinolol in Caco-2 cells.
AB  - To investigate the potential interaction between selected ingredients of
      grapefruit juice and, the transport of talinolol, a P-gp substrate, across Caco-2
      cells monolayers was determined in the absence and presence of distinct
      concentrations of grapefruit juice, bergamottin, 6',7'-dihydroxybergamottin,
      6',7'-epoxybergamottin, naringin, and naringenin. Talinolol permeability was
      selectively inhibited by grapefruit juice and its components. The furano
      coumarin, 6',7'-epoxybergamottin, was the most potent inhibitor (IC(50) = 0.7
      microM), followed by 6',7'-dihydroxybergamottin (IC(50) = 34 microM) and
      bergamottin that did not show any inhibition at concentrations up to 10 microM.
      The flavonoid aglycone naringenin was around 10-fold more potent than its
      glycoside naringin with IC(50) values of 236 and 2409 microM, respectively. The
      flavonoids and furanocoumarins tested in this study are in the same range of
      concentration they are present in the juice contributing, therefore, for the
      overall inhibitory effect of GFJ on P-gp activity. The in vitro data suggest that
      compounds present in grapefruit juice are able to inhibit the P-gp activity
      modifying the disposition of drugs that are P-gp substrates such as talinolol.

PMID- 17542019
TI  - In vitro assessment of cytochrome P450 inhibition: strategies for increasing
      LC/MS-based assay throughput using a one-point IC(50) method and multiplexing
      high-performance liquid chromatography.
AB  - A fast and robust LC/MS-based cytochrome P450 (CYP) inhibition assay, using human
      liver microsomes, has been fully developed and validated for the major human
      liver CYPs. Probe substrates were phenacetin, diclofenac, S-mephenytoin, and
      dextromethorphan for CYP1A2, CYP2C9, CYP2C19, and CYP2D6, respectively. Midazolam
      and testosterone were chosen for CYP3A4. Furafylline, sulfaphenazole,
      tranylcypromine, quinidine, and ketoconazole were identified as positive control
      inhibitors for CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4, respectively. To
      increase the throughput of the assay, a one-point method was developed, using
      data from CYP inhibition assays conducted at one concentration (i.e., 10 microM),
      to estimate the drug concentration at which the metabolism of the CYP probe
      substrate was reduced by 50% (IC(50)). The IC(50) values from the one-point assay
      were validated by correlating the results with IC(50) values that were obtained
      with a traditional eight-point concentration-response curve. Good correlation was
      achieved with the slopes of the trendlines between 0.95 and 1.02 and with R(2)
      between 0.77 and 1.0. Throughput was increased twofold by using a Cohesive
      multiplexing high-performance liquid chromatography system. The one-point IC(50)
      estimate is useful for initial compound screening, while the full concentration
      response IC(50) method provides detailed CYP inhibition data for later stages of
      drug development.

PMID- 17542020
TI  - Stabilization of proteins by recombinant human gelatins.
AB  - Porcine gelatins have been widely used as stabilizers of macromolecular based
      pharmaceuticals but the mechanism by which they stabilize has not been precisely
      established. Their variability and immunogenicity, however, make them less than
      ideal excipients. In this work, we take advantage of the availability of
      recombinant human gelatins (rhGs) to explore the mechanism by which they may
      stabilize proteins. Three model recombinant proteins, human serum albumin (HSA),
      bovine granulocyte colony stimulating factor (bGCSF), and human fibroblast growth
      factor-20 (FGF-20) that display a range of isoionic points have been selected for
      this study. The interaction of these model proteins with four different molecular
      weight rhGs and porcine gelatin was studied using a variety of biophysical
      techniques including fluorescence, CD and second derivative UV spectroscopy to
      monitor tertiary and secondary structure as a function of temperature. The 8.5,
      25, and 100 kDa rhGs had the greatest effect on conformational and colloidal
      stability of HSA. The 8.5, 25, and 50 kDa rhGs also increased the T(0) of
      aggregation of bGCSF and FGF-20. Experiments to probe the mechanism of
      interaction of model proteins with rhGs suggest that the rhGs might interact with
      the partially unfolded states of target proteins through a combination of
      electrostatic and other intermolecular mechanisms to inhibit aggregation.

PMID- 17542021
TI  - Influence of crystal structure on the tableting properties of n-alkyl 4
      hydroxybenzoate esters (parabens).
AB  - Certain crystallographic features, such as the existence of slip planes, can
      greatly facilitate the ability of crystals to deform plastically. An
      investigation of the relationship between the slip planes and the tableting
      performance of the crystals of methyl, ethyl, n-propyl, and n-butyl 4
      hydroxybenzoate (parabens) was conducted. The absence of slip planes in methyl
      paraben crystal structure results in significantly poorer tableting performance
      than the other three parabens. While slip planes are present in the crystal
      structures of ethyl, propyl, and butyl parabens, they exhibited different
      plasticity as confirmed by crystal free volume analysis, crystal nano-indentation
      hardness, and Heckel analysis. Sieved fraction, 150-250 microm, of each paraben
      powder was compressed into tablets under different conditions. Tablet tensile
      strength, porosity, and Indices of tableting performance (ITP) were obtained.
      Under the same compaction pressure, tablet tensile strength was higher for
      crystals with higher plasticity. Tableting performance, assessed using the ITP,
      also improved with increasing crystal plasticity. The results confirm that high
      levels of plasticity, which can result from the presence of slip planes in
      crystal lattice, plays a critical role in the formation of strong and intact
      tablets by means of powder compaction.

PMID- 17542022
TI  - Variability in Caco-2 and MDCK cell-based intestinal permeability assays.
AB  - Models predictive of intestinal drug absorption are important in drug development
      to identify compounds with promising biopharmaceutical properties. Since
      permeability is a factor affecting absorption, cell culture models (e.g., Caco-2,
      MDCK) have been developed to predict drug transport from the intestinal lumen
      into the bloodstream. The differences as to how the assays are performed, along
      with heterogeneity of the cell lines, have lead to different permeability values
      for the same drug. Transport and metabolic properties of cultured cells can vary
      due to culture conditions, seeding density, passage number, confluency, filter
      support, monolayer age, and stage of differentiation. During the transport
      experiment, cell absorption properties can change due to the composition and pH
      of the transport buffer, solute concentration and solubility, temperature,
      additives and/or cosolvents, agitation, sampling schedule, sink conditions, and
      analytical methods. Such variability within a laboratory can be avoided by
      characterizing a cell culture method and setting acceptance criteria in terms of
      monolayer integrity, passive transport, and active transport. The repeated
      evaluation of reference compounds will then facilitate intra-laboratory
      comparisons.

PMID- 17542023
TI  - Importance of divalent cations in nanolipoplex gene delivery.
AB  - Gene therapy is a promising therapeutic strategy to combat genetic or acquired
      diseases at their root cause rather than just treating symptoms. It is well
      recognised that there is an urgent need for non-toxic and efficient gene delivery
      vectors to fully exploit the current potential of gene therapy in molecular
      medicine. Cell-specific targeting of bioactive nucleotides is a prerequisite to
      attain the concentration of nucleic acids required for therapeutic efficacy in
      the target tissue. Many metal ions such as Mg2+, Mn2+, Ba2+ and, most
      importantly, Ca2+ have been demonstrated to have significant roles in gene
      delivery. These inorganic cations show low toxicity, good biocompatibility and
      promise for controlled delivery properties, thus presenting a new alternative to
      toxic and immunogenic carriers. Recently, inorganic nanoparticles alone, or in
      combination with a colloidal particulate system such as nanoliposome, an advanced
      approach to gene delivery, were found to exert a positive effect on gene
      transfer. In this report, the role of the divalent cations in nucleic acid
      delivery, particularly with respect to the potential improvement of transfection
      efficiency of nanolipoplexes, is reviewed.

PMID- 17542024
TI  - Micropapillary bladder cancer: a review of the University of Texas M. D. Anderson
      Cancer Center experience with 100 consecutive patients.
AB  - BACKGROUND: Micropapillary bladder carcinoma is a rare variant of urothelial
      carcinoma. To improve understanding of this disease, the authors performed a
      retrospective review of their experience. METHODS: The authors reviewed the
      records of 100 consecutive patients with micropapillary bladder cancer who were
      evaluated at The University of Texas M. D. Anderson Cancer Center. RESULTS: The
      mean age of the patients was 64.7 years, with a male:female ratio of 10:1. The
      TNM stage of disease at the time of presentation was Ta in 5 patients, carcinoma
      in situ (CIS) in 4 patients, T1 in 35 patients, T2 in 26 patients, T3 in 7
      patients, T4 in 6 patients; N+ in 9 patients, and M+ in 8 patients. Kaplan-Meier
      estimates of 5-year and 10-year overall survival (OS) rates were 51% and 24%,
      respectively. Bladder-sparing therapy with intravesical bacillus Calmette-Guerin
      therapy was attempted in 27 of 44 patients with nonmuscle-invasive disease; 67%
      (18 patients) developed disease progression (>or=cT2), including 22% who
      developed metastatic disease. Of 55 patients undergoing radical cystectomy for
      surgically resectable disease (<or=cT4a), 23 received neoadjuvant chemotherapy
      and 32 were treated with initial cystectomy, with no significant difference noted
      in stage distribution between the 2 groups. For the 23 patients treated with
      neoadjuvant chemotherapy, the median OS was 43.2 months with 32% of patients
      still alive at 5 years. For the 32 patients treated with initial cystectomy, the
      median survival had not been reached at the time of last follow-up, with 71%
      still alive at 5 years. CONCLUSIONS: Micropapillary bladder cancer is associated
      with a poor prognosis. Intravesical therapy appears to be ineffective in this
      disease and patients with surgically resectable disease should be offered early
      radical cystectomy.

PMID- 17542025
TI  - A statistical pattern recognition approach for determining cellular viability and
      lineage phenotype in cultured cells and murine bone marrow.
AB  - BACKGROUND: Cellular binding of annexin V and membrane permeability to 7
      aminoactinomycin D (7AAD) are important tools for studying apoptosis and cell
      death by flow cytometry. Combining viability markers with cell surface marker
      expression is routinely used to study various cell lineages. Current
      classification methods using strict thresholds, or "gates," on the fluorescent
      intensity of these markers are subjective in nature and may not fully describe
      the phenotypes of interest. We have developed objective criteria for phenotypic
      boundary recognition through the application of statistical pattern recognition.
      This task was achieved using artificial neural networks (ANNs) that were trained
      to recognize subsets of cells with known phenotypes, and then used to determine
      decision boundaries based on statistical measures of similarity. This approach
      was then used to test the hypothesis that erythropoietin (EPO) inhibits apoptosis
      and cell death in erythroid precursor cells in murine bone marrow. METHODS: Our
      method was developed for classification of viability using an in vitro cell
      system and then applied to an ex vivo analysis of murine late-stage erythroid
      progenitors. To induce apoptosis and cell death in vitro, an EPO-dependent human
      leukemic cell line, UT-7(EPO) cells were incubated without recombinant human
      erythropoietin (rhEPO) for 72 h. Five different ANNs were trained to recognize
      live, apoptotic, and dead cells using a "known" subset of the data for training,
      and a K-fold cross validation procedure for error estimation. The ANNs developed
      with the in vitro system were then applied to classify cells from an ex vivo
      study of rhEPO treated mice. Tg197 (human tumor necrosis-alpha transgenic mice, a
      model of anemia of chronic disease) received a single s.c. dose of 10,000 U/kg
      rhEPO and femoral bone marrow was collected 1, 2, 4, and 8 days after dosing.
      Femoral bone marrow cells were stained with TER-119 PE, CD71 APC enable
      identification of erythroid precursors, and annexin V FITC and 7AAD to identify
      the apoptotic and dead cells. During classification forward and side angle light
      scatter were also input to all pattern recognition systems. RESULTS: Similar
      decision boundaries between live, apoptotic, and dead cells were consistently
      identified by the neural networks. The best performing network was a radial basis
      function multi-perceptron that produced an estimated average error rate of 4.5%
      +/- 0.9%. Using these boundaries, the following results were reached: depriving
      UT-7(EPO) cells of rhEPO induced apoptosis and cell death while the addition of
      rhEPO rescued the cells in a dose-dependent manner. In vivo, treatment with rhEPO
      resulted in an increase of live erythroid cells in the bone marrow to 119.8% +/-
      9.8% of control at the 8 day time point. However, a statistically significant
      transient increase in TER-119(+) CD71(+) 7AAD(+) dead erythroid precursors was
      observed at the 1 and 2 day time points with a corresponding decrease in TER
      119(+) CD71(+) 7AAD(-) Annexin V(-) live erythroid precursors, and no change in
      the number of TER-119(+) CD71(+) annexin V(+) 7AAD(-) apoptotic erythroid
      precursors in the bone marrow. CONCLUSIONS: A statistical pattern recognition
      approach to viability classification provides an objective rationale for setting
      decision boundaries between "positive" and "negative" intensity measures in
      cytometric data. Using this approach we have confirmed that rhEPO inhibits
      apoptosis and cell death in an EPO dependent cell line in vitro, but failed to do
      so in vivo, suggesting EPO may not act as a simple antiapoptotic agent in the
      bone marrow. Rather, homeostatic mechanisms may regulate the pharmacodynamic
      response to rhEPO.

PMID- 17542026
TI  - Flow sorting from organ material by intracellular markers.
AB  - BACKGROUND: Fluorescence-activated cell sorting (FACS) is an attractive technique
      for gene or protein expression studies in rare cell populations. For cell types
      where specific surface markers are not known, intracellular markers can be used.
      However, this approach is currently held to be difficult, as the required
      fixation and permeabilization may cause protein modification and RNA degradation.
      METHODS AND RESULTS: Using the rat thyroid gland as model, rare (parafollicular)
      and frequent (follicular) endocrine cell types were sorted based on
      immunostaining for intracellular calcitonin peptide and thyroglobulin protein
      expression. The sorted cells were compatible with Western blot analysis of
      proteins, immunoassay detection of calcitonin peptide hormone and RT-PCR.
      CONCLUSION: We developed a robust FACS protocol that allows flow sorting of rare
      cells from dissociated organ material, based on intracellular markers. Our FACS
      protocol is compatible with downstream analysis of proteins, peptides, and mRNA
      in the sorted cells.

PMID- 17542027
TI  - High-throughput screening and characterization of clones selected from phage
      display libraries.
AB  - BACKGROUND: Clones from phage display libraries are generally selected by a
      number of rounds of panning and regrowth, followed by primary screening to
      identify hits and secondary characterization to identify clones with optimal
      affinity and specificity. Because functional screening for binding or other
      activity can be material-, time-, and labor-intensive, sequencing is often used
      to identify the emergence of a consensus sequence prior functional
      characterization. However, the consensus sequence is not always the optimal one
      because factors such as phage growth rates, nonspecific binding, and other
      selection pressures can bias the selection process. METHODS: To improve function
      based phage display library screening and characterization, we developed a
      multiplexed approach employing optically-encoded microsphere arrays and flow
      cytometry. RESULTS: We show that capture of phage from crude culture supernatants
      enables the efficient screening of binding activity and the evaluation of binding
      avidity. The approach uses small volumes and a homogeneous no-wash format that
      minimizes reagent consumption and sample handling. The use of optically-encoded
      microspheres allows many phage to be screened simultaneously, greatly increasing
      throughput. CONCLUSIONS: This approach is flexible, supporting primary and
      secondary screening for a range of functional assays, and scalable, potentially
      supporting the screening of thousands to hundreds of thousands of clones per
      hour.

PMID- 17542028
TI  - Duplexed, bead-based competitive assay for inhibitors of protein kinases.
AB  - BACKGROUND: Many cellular signal transduction cascades have protein kinases as
      critical components. Small molecule protein kinase inhibitors can be effective as
      laboratory probes and drugs. Methods that allow two or more kinases to be
      evaluated simultaneously for inhibition by a small molecule would allow
      unequivocal tests of specificity and selectivity of action of the small molecule.
      METHODS: Two hexahistidine-tagged activin receptor-like kinases were expressed in
      E. coli, purified, and bound to nickel beads. A fluorescent kinase ligand (F-KL)
      that binds to the ATP-binding site of these kinases with nanomolar affinity was
      developed. Binding of F-KL with kinase on the bead made the beads bright, and
      inhibitors decreased the brightness. RESULTS: A test panel of 17 nonfluorescent
      kinase inhibitors, spanning two orders of magnitude affinity for the kinases,
      gave K(d) values for the kinases that correlated well with a fluorescence
      polarization assay. Results were obtained for the kinases in duplex, using an
      autosampler to send beads from a 96-well plate to a flow cytometer in a format
      suitable for high throughput screening. CONCLUSIONS: Inhibitors of kinases can be
      measured in duplex in a high throughput format by flow cytometry, if a suitable
      fluorescent ligand is available.

PMID- 17542029
TI  - Tracking molecular particles in live cells using fuzzy rule-based system.
AB  - Recent development of detection techniques of molecular particles in live cells
      has stimulated interest in developing the new powerful techniques to track the
      molecular particles in live cells. One special type of cellular microscopy images
      is about the formation and transportation of clathrin-coated pits and vesicles.
      Clathrin-coated pits are very important in studying the behavior of proteins and
      lipids in live cells. To answer the question, whether there exist "hot spots" for
      the formation of Clathrin-coated pits or the pits and arrays formed randomly on
      the plasma membrane, it is necessary to track many hundreds of individual pits
      dynamically in live-cell microscope movies to capture and monitor how pits and
      vesicles were formed. Therefore, a motion correspondence algorithm based on fuzzy
      rule-based system is proposed to resolve the problem of ambiguous association
      encountered in these dynamic, live-cell images of clathrin assemblies. Results
      show that this method can accurately track most of the particles in the high
      volume images.

PMID- 17542030
TI  - Are staff reliable informants? Identifying the triggers to challenging behaviours
      in dementia.

PMID- 17542031
TI  - Influence of functional groups on the site-selective dissociation of adenine upon
      low-energy electron attachment.

PMID- 17542032
TI  - Solvent-dependent oxidation of a (pyridylmethyl)amino ligand by FeCl3 to give a
      water-soluble blue fluorophore.

PMID- 17542033
TI  - Catalytic asymmetric formation of delta-lactones by [4+2] cycloaddition of
      zwitterionic dienolates generated from alpha,beta-unsaturated acid chlorides.

PMID- 17542034
TI  - Nitroxylcob(III)alamin: synthesis and X-ray structural characterization.

PMID- 17542035
TI  - Stepwise intermetal borylene transfer: synthesis and structure of mono- and
      dinuclear cobalt-borylene complexes.

PMID- 17542036
TI  - Gold-catalyzed intramolecular redox reaction of sulfinyl alkynes: efficient
      generation of alpha-oxo gold carbenoids and application in insertion into R--CO
      bonds.

PMID- 17542037
TI  - The relationship between nitric oxide and leptin in the lung of rat with
      streptozotocin-induced diabetes.
AB  - Lung structural changes and immunoreactivity of endothelial (eNOS)- and inducible
      nitric oxide synthase (iNOS) were investigated by light microscopy in lungs of
      treated and untreated diabetic rats. Diabetes was induced by a single
      intraperitoneal (i.p.) injection of 65 mg kg(-1) streptozotocin (STZ) in Wistar
      albino male rats. Diabetic rats received daily i.p. doses of dexamethasone (2 mg
      kg(-1)), leptin (0.5 microg kg(-1)) and intramuscular insulin (20 U kg(-1)) or a
      combination of these drugs for 1 week starting 4 weeks after the STZ injections.
      After treatment, the blood levels of glucose, leptin, insulin and nitrate/nitrite
      (NO(3) (-)/NO(2) (-)) were measured. Dilatation of alveoli and alveolar ducts,
      partial alveolar wall thickening and increased eNOS- and iNOS characterized the
      diabetic rat lungs. High blood glucose and nitrate/nitrite levels as well as low
      insulin and leptin levels were also present. Treatment with insulin,
      dexamethasone and a combination of these drugs resulted in improvement of the
      structural and immunohistochemical abnormalities. The most effective treatment
      was insulin therapy. Leptin administration resulted in increased relative amounts
      of extracellular material, which led to noticeable respiratory efficiency in the
      diabetic rat lungs. All treatments except leptin lowered blood glucose levels.
      The combination of insulin and dexamethasone increased blood leptin and insulin,
      while the remaining diabetic rats had blood with low leptin and insulin
      concentrations. These results suggest that therapy with insulin plus
      dexamethasone but not therapy with leptin is beneficial for diabetics.

PMID- 17542038
TI  - Glutamine supplementation prevents exercise-induced neutrophil apoptosis and
      reduces p38 MAPK and JNK phosphorylation and p53 and caspase 3 expression.
AB  - We have previously shown that a single session of exercise induces DNA
      fragmentation, mitochondrial membrane depolarization, increases expression of pro
      apoptotic genes (bax and bcl-xS) and decreases expression of anti-apoptotic genes
      (bcl-xL) in rat neutrophils. Glutamine supplementation had a protective effect in
      the apoptosis induced by a single session of exercise. The mechanism involved in
      the effect of single session of exercise to induce apoptosis was investigated by
      measuring expression of p53 and caspase 3 and phosphorylation of p38 mitogen
      activated protein kinases (MAPK) and cJun NH(2)-terminal kinase (JNK) in
      neutrophils from rats supplemented or not with glutamine. Exercise was carried
      out on a treadmill for 1 h and the rats were killed by decapitation. Neutrophils
      were obtained by intraperitoneal (i.p.) lavage with PBS, 4 h after injection of
      oyster glycogen solution. Glutamine supplementation (1g per Kg b.w.) was given by
      gavage 1 h before the exercise session. Gene expression and protein
      phosphorylation were then analyzed by reverse transcriptase chain reaction (RT
      PCR) and Western blotting, respectively. A single session of exercise increased
      p38 MAPK and JNK phosphorylation and p53 and caspase 3 expression. Glutamine
      supplementation partially prevented the increase in p38 MAPK and JNK
      phosphorylation and p53 expression, and fully abolished the increase in caspase 3
      expression. Thus, neutrophil apoptosis induced by a single session of exercise is
      accompanied by increased p53 and caspase 3 expression and p38 MAPK and JNK
      phosphorylation. Glutamine supplementation prevents these effects of exercise and
      reduces apoptosis.

PMID- 17542039
TI  - A classification system for selective intrauterine growth restriction in
      monochorionic pregnancies according to umbilical artery Doppler flow in the
      smaller twin.
AB  - OBJECTIVES: To evaluate a classification of selective intrauterine growth
      restriction (sIUGR) in monochorionic (MC) twins based on the characteristics of
      umbilical artery (UA) Doppler flow in the smaller twin, in terms of association
      with clinical outcome and with the pattern of placental anastomoses. METHODS: One
      hundred and thirty-four MC twins diagnosed with sIUGR at 18-26 weeks were
      classified as Type I (UA Doppler with positive diastolic flow, n = 39), Type II
      (persistent absent or reversed end-diastolic flow, n = 30) and Type III
      (intermittent absent or reversed end-diastolic flow, n = 65). Perinatal outcome,
      placental sharing and the pattern of anastomoses were compared with those in 76
      uncomplicated MC twins. RESULTS: Mean gestational age at delivery was 35.5
      (range, 30-38) weeks in controls, 35.4 (range, 16-38) weeks in Type I, 30.7
      (range, 27-40) weeks in Type II (P < 0.0001) and 31.6 (range, 23-39) weeks in
      Type III (P < 0.0001) pregnancies. Fetal weight discordance was significantly
      higher in Type II (38%) and Type III (36%) than in Type I (29%) (P < 0.0001)
      pregnancies. Deterioration of the growth-restricted fetus occurred in 90% of Type
      II cases, compared with 0% and 10.8% of Types I and III, respectively (P <
      0.001). Unexpected intrauterine fetal death of the smaller twin occurred in 15.4%
      of Type III cases, compared with 2.6% and 0% of Types I and II respectively (P <
      0.05). Parenchymal brain lesions in the larger twin were observed in 19.7% of
      Type III cases and less than 5% in the other groups (P < 0.05). Placental
      discordance (larger/smaller) was 1.3 in controls, compared with 1.8, 2.6 and 4.4
      in Types I, II and III, respectively (P < 0.01). The proportion of cases with
      arterioarterial anastomoses > 2 mm in diameter was 55% in controls, 70% in Type
      I, 18% in Type II (P < 0.01) and 98% in Type III (P < 0.01). CONCLUSION: sIUGR
      can be classified on the basis of umbilical artery Doppler into three types that
      correlate with different clinical behavior and different patterns of placental
      anastomoses. This classification may be of help in clinical decision-making and
      when comparing clinical studies.

PMID- 17542040
TI  - Mechanisms controlling function in the clasp and sling regions of porcine lower
      oesophageal sphincter.
AB  - BACKGROUND: Characterization of functional differences between lower oesophageal
      sphincter (LOS) clasp and sling muscles might aid the development of more
      specific pharmacological and surgical approaches for the treatment of motility
      disorders. METHODS: Circular LOS strips from 25 adult pigs were studied in organ
      baths to compare the physiology of clasp and sling fibres. RESULTS: Sling strips
      developed greater tone than clasp fibres (mean(s.e.m.) 7.59(0.89) versus
      4.72(0.67) g; P = 0.017). LOS tone was more dependent on extracellular calcium in
      clasp strips and on the activity of cholinergic enteric motor neurones (EMNs) in
      sling strips. The amplitude of maximal relaxation caused by electrical field
      stimulation (EFS, 3Hz) of EMNs was greater in clasp strips (mean(s.e.m.)
      74.5(2.3) versus 58.1(2.2) per cent of tone; P < 0.001). EFS-induced relaxation
      was reduced in clasp fibres and fully blocked in sling fibres by nitrergic
      blockade with 10 micromol/l 1H-[1,2,4]oxadiazole-[4,3-alpha]quinoxalin-1-one
      (ODQ). The amplitude of EFS cholinergic responses was significantly greater in
      sling fibres. In the clasp region, relaxation caused by stimulation of EMNs with
      100 micromol/l nicotine was reduced by ODQ. In sling fibres, nicotine induced
      relaxation at rest and cholinergic contraction following ODQ. CONCLUSION: Clasp
      and sling fibres of the porcine LOS show marked intrinsic functional differences.
      This should be considered when developing more specific approaches to human LOS
      motility disorders.

PMID- 17542041
TI  - Intra-anal application of L-erythro methoxamine gel increases anal resting
      pressure in patients with incontinence.
AB  - BACKGROUND: This study examined the effects of a single dose of intra-anal L
      erythro methoxamine on mean anal resting pressure (MARP) and cardiovascular
      variables in patients with faecal incontinence. METHODS: Patients had anorectal
      physiology tests and ultrasonography before participating. Six patients received
      0.3 and 1 per cent gels on separate days, two patients received 0.3 per cent gel,
      and two patients received 1 per cent gel. MARP, blood pressure, pulse rate and
      plasma drug concentrations were measured for 6 h after application. RESULTS:
      Intra-anal 0.3 per cent gel caused a rapid, significant rise in MARP lasting 2 h
      (P = 0.036). In four of these patients, the response was sufficient to increase
      MARP to within the normal range at 2 h. Application of 1 per cent gel caused a
      significant rise in MARP for 4 h after application (P = 0.028). There was a
      significant decrease in pulse at 2 and 1 h respectively after application of 0.3
      and 1 per cent gels. CONCLUSION: Intra-anal application of L-erythro methoxamine
      can be used to increase MARP in patients with faecal incontinence. Application of
      1 per cent L-erythro methoxamine gel produced a rapid, sustained rise in MARP,
      which raises the possibility of therapeutic application.

PMID- 17542042
TI  - Characterization of brain metastases using high-resolution magic angle spinning
      MRS.
AB  - The objectives of this study were to (a) explore the spectral characteristics of
      brain metastases, focusing on the origin of the primary cancer, and (b) evaluate
      the correlation with clinical outcome using multivariate analysis. High
      resolution magic angle spinning (HR-MAS) MR spectra (n = 26) were obtained from
      16 patients with brain metastases using a Bruker Avance DRX600 instrument.
      Standard pulse-acquired and spin-echo (TE 32 and 285 ms) (1)H spectra were
      obtained. These were examined using principal component analysis (PCA) and
      partial least squares regression analysis (PLS) relating spectral data to
      clinical outcome. The PCA score plot of pulse-acquired HR-MAS spectra showed a
      trend of clustering due to the origin of the metastases, mainly based on
      differences in the lipid signals at 1.3 and 0.9 ppm. With PLS, spectra of
      patients who died less than 5 months after surgery appeared to cluster in the
      lower left quadrant of the score plot. These preliminary results on brain
      metastasis classification and prediction of survival must be validated in a
      larger patient cohort. However, the possibility of differentiating metastases
      according to origin and predicting survival on the basis of HR-MAS spectra
      suggests that this method may be useful for diagnosing and planning treatment for
      brain metastases and also for guiding decisions about terminating further
      treatment.

PMID- 17542043
TI  - Microfluidics in amino acid analysis.
AB  - Microfluidic devices have been widely used to derivatize, separate, and detect
      amino acids employing many different strategies. Virtually zero-dead volume
      interconnections and fast mass transfer in small volume microchannels enable
      dramatic increases in on-chip derivatization reaction speed, while only minute
      amounts of sample and reagent are needed. Due to short channel path, fast
      subsecond separations can be carried out. With sophisticated miniaturized
      detectors, the whole analytical process can be integrated on one platform. This
      article reviews developments of lab-on-chip technology in amino acid analysis, it
      shows important design features such as sample preconcentration, precolumn and
      postcolumn amino acid derivatization, and unlabeled and labeled amino acid
      detection with focus on advanced designs. The review also describes important
      biomedical and space exploration applications of amino acid analysis on
      microfluidic devices.

PMID- 17542044
TI  - Research in Musculoskeletal Care: the Dudley interdisciplinary experience.

PMID- 17542045
TI  - Patient-reported outcome II: selecting appropriate measures for musculoskeletal
      care.
AB  - The first article in this series outlined the important contribution that well
      developed patient reported outcome measures (PROMs) can make to healthcare,
      clinical decision making and evaluation. The increasing focus on patient reported
      health means that there are now hundreds of questionnaires available; selecting
      the appropriate measure is both challenging and essential. This article will
      introduce potential users of PROMs to key information to consider when selecting
      and using PROMs in research, routine practice or quality assurance. Important
      concepts, such as measurement reliability, validity and responsiveness to
      important change in health, will be explored and illustrated with examples from
      musculoskeletal healthcare. Practical properties, such as acceptability and
      feasibility, will also be introduced.

PMID- 17542046
TI  - Evidence-based management for polymyalgia rheumatica for rheumatology
      practitioners, nurses and physiotherapists.
AB  - Evidence-based practice is an increasingly popular term, used in a variety of
      clinical settings and situations. Practitioners are encouraged to use best
      evidence as part of clinical decision-making when caring for individual patients.
      This evidence, combined with practitioner expertise and knowledge, aims to inform
      practice, ensuring that accurate, effective and safe treatment options are
      utilized.

PMID- 17542047
TI  - An analysis of safety and tolerability data from controlled, comparative studies
      of quetiapine in patients with schizophrenia, focusing on extrapyramidal
      symptoms.
AB  - AIM: This analysis evaluated the tolerability profile of quetiapine using data
      from all comparative controlled studies in patients with schizophrenia or related
      disorders in the AstraZeneca clinical trials database, focusing on extrapyramidal
      symptoms (EPS). METHODS: Adverse event (AE) data from randomised, double-blind,
      controlled studies in the AstraZeneca clinical trials database were pooled,
      allowing comparison of quetiapine (mean daily doses 357-496 mg/day) with placebo,
      haloperidol (10.4 mg/day), risperidone (5.5 mg/day) or chlorpromazine (552
      mg/day). Incidence of EPS-related AEs in relation to quetiapine dose was also
      analysed using a subset of data from fixed-dose studies. RESULTS: Data from 4956
      patients were analysed. Quetiapine was well tolerated, and did not increase EPS
      related AEs when compared with placebo (9.6 vs. 10.6%, respectively). The
      incidence of EPS-related AEs with quetiapine was consistent across the dose range
      (4.2-13.2% vs. 11.1% with placebo). Patients receiving haloperidol, risperidone
      and chlorpromazine experienced significantly higher levels of EPS-related AEs
      than those on quetiapine. The most common quetiapine- associated AEs, with
      significantly higher incidence than placebo, were sedation, somnolence and
      orthostatic hypotension. CONCLUSION: Quetiapine is generally well tolerated in
      patients with schizophrenia or related disorders, with placebo-level EPS-related
      AEs. Quetiapine has a more favourable EPS profile than haloperidol,
      chlorpromazine or risperidone.

PMID- 17542052
TI  - New estimates of the prevalence of neurological and sensory sequelae and
      mortality associated with congenital cytomegalovirus infection.
AB  - Congenital CMV is a major cause of neurological and sensory impairment in
      children. Reliable estimates of the prevalence of permanent sequelae and
      mortality associated with congenital CMV are needed to guide development of
      education and prevention programmes and to gauge the financial costs associated
      with this disease. To calculate such estimates, this review used data solely from
      studies in which children with congenital CMV were identified through universal
      screening. Based on 15 studies with a total of 117 986 infants screened, the
      overall CMV birth prevalence estimate was 0.7%. The percentage of infected
      children with CMV-specific symptoms at birth was 12.7%. The percentage of
      symptomatic children with permanent sequelae was 40-58%. The percentage of
      children without symptoms at birth who developed permanent sequelae was estimated
      to be 13.5%. The true burden of congenital CMV infection is unclear because data
      on important outcomes, such as visual impairment, are lacking and follow-up of
      infected children has been too short to fully identify late-onset sequelae.
      Therefore, the estimates of permanent sequelae associated with congenital CMV
      presented here are likely underestimates. Future studies should extend follow-up
      of CMV-infected children identified through universal screening and include the
      evaluation of visual impairment.

PMID- 17542053
TI  - Biological mechanisms of vertical human immunodeficiency virus (HIV-1)
      transmission.
AB  - In the absence of interventions, 30-45% of exposed infants acquire human
      immunodeficiency virus type 1 (HIV-1) through mother-to-child transmission. It
      remains unclear why some infants become infected while others do not, despite
      significant exposure to HIV-1 in utero, during delivery and while breastfeeding.
      Here we discuss the correlates of vertical transmission with an emphasis on
      factors that increase maternal HIV-1 levels, either systemically or locally in
      genital secretions and breast milk. Immune responses may influence maternal viral
      load, and data suggest that maternal neutralising antibodies reduce infection
      rates. In addition, infants may be capable of mounting HIV-specific cellular
      immune responses. We propose that both humoral and cellular responses are
      necessary to reduce infection because cell-free as well as cell-associated virus
      appears to play a role in vertical transmission. These distinct forms of the
      virus may be targeted most effectively by different components of the immune
      system. We also discuss the use of antiretrovirals to reduce transmission,
      focusing on the mechanisms of action of regimens currently used in developing
      country settings. We conclude that prevention relies not only on reducing
      maternal HIV-1 levels within blood, genital tract and breast milk, but also on
      pre- and/or post-exposure prophylaxis to the infant. However, HIV-1 has the
      capacity to mutate under drug pressure and rapidly acquires mutations conferring
      antiretroviral resistance. This review concludes with data on persistence of low
      level resistance after delivery as well as recent guidelines for maternal and
      infant regimens designed to limit resistance.

PMID- 17542054
TI  - A novel way of liver preservation improves rat liver viability upon reperfusion.
AB  - BACKGROUND/AIM: Currently, the liver is cold-preserved at 0 approximately 4
      degrees C for experimental and clinical purposes. Here, we investigated whether
      milder hypothermia during the initial phase of the preservation period was
      beneficial for liver viability upon reperfusion. METHODS: In the first set of
      experiments, rat livers were preserved either conventionally in clinically used
      histidine-trypthopan-ketoglutarate (HTK) solution (Group A: 45 min and Group B:
      24 h) or by slow cooling HTK solution (from 13 degrees C to 3 degrees C) during
      the initial 45 min of preservation (Group C: 24 h). In the second set of
      experiments, additional groups of livers were evaluated: Group BB--preservation
      according to Group B and Group CC--preservation according to Group C. Further,
      some livers were preserved at 13 degrees C for 24 h. Livers were then reperfused
      using a blood-free perfusion model. RESULTS: Bile production was approximately 2
      fold greater in Group C compared to Group B. Alanine transaminase (ALT) and
      aspartate transaminase (AST) release into perfusate were 2 approximately 3-fold
      higher in Group B compared to Group C. No significant differences were found in
      ALT and AST release between Group C and Group A. Livers in Group CC compared to
      Group BB exhibited significantly lower portal resistance, greater oxygen
      consumption and bromosulfophthalein excretion into bile and lower lactate
      dehydrogenase (LDH) release into perfusate. Histological evaluation of tissue
      sections in Group BB showed parenchymal dystrophy of hepatocytes, while dystrophy
      of hepatocytes was absent in Group CC. Livers preserved at 13 degrees C for 24 h
      exhibited severe ischemic injury. CONCLUSION: These results suggest that the
      conventional way of liver preservation is not suitable at least for rat livers
      and that slow cooling of HTK solution during the initial phase of cold storage
      can improve liver viability during reperfusion.

PMID- 17542055
TI  - Pressure from the lips and the tongue in children with class III malocclusion.
AB  - OBJECTIVE: To discuss possible relationships between class III malocclusion and
      perioral forces by measuring the pressure from the lips and the tongue of
      children with class III malocclusion. METHODS: Thirty-one children with class III
      malocclusion were investigated and their perioral forces were measured at rest
      and during swallowing under natural head position by a custom-made miniperioral
      force computer measuring system. RESULTS: The resting pressures exerted on the
      labial side and palatine side of the upper left incisor, as well as the labial
      side and lingual side of the lower left incisor, were 0 g/cm(2), 0 g/cm(2), 0.57
      g/cm(2) and 0.23 g/cm(2), respectively. Correspondingly, the swallowing forces
      were 2.87 g/cm(2), 5.97 g/cm(2), 4.09 g/cm(2) and 7.89 g/cm(2), respectively. No
      statistical difference between muscular pressure and gender existed. During
      swallowing, the lingual forces were significantly higher than the labial forces
      (P<0.01), however, at rest there was no significantly different force between
      these two sides. Compared to the normal occlusion patients, children with class
      III malocclusion had lower perioral forces. The upper labial resting forces
      (P<0.01), the lower labial resting forces (P<0.05) and all the swallowing
      pressures from the lips and the tongue (P<0.01) showed statistical differences
      between the two different occlusion conditions. Meanwhile, no significant
      difference was found for the resting pressure from the tongue between class III
      malocclusion and normal occlusion. CONCLUSION: Patients with class III
      malocclusion have lower perioral forces and this muscle hypofunction may be
      secondary to the spatial relations of the jaws. The findings support the spatial
      matrix hypothesis.

PMID- 17542056
TI  - Determination of fluorinated quinolone antibacterials by ion chromatography with
      fluorescence detection.
AB  - For preparing fluorinated quinolone antibiotic medicine locally used in
      stomatology, simultaneous determination of norfloxacin, ciprofloxacin, and
      enoxacin was carried out by multiphase ion chromatography with fluorescence
      detection. Quinolone antibiotics were separated by Dionex OmniPac PAX-500 column
      with an eluent of 15 mmol/L H(2)SO(4) and 35% methanol (v/v) at a flow-rate of
      1.0 ml/min and detected with fluorescence with excitation and emission wave
      lengths of 347 nm and 420 nm respectively. The detection limits (S/N=3) of
      norfloxacin, ciprofloxacin and enoxacin were 50, 105 and 80 ng/ml respectively.
      The relative standard deviations of retention time, peak area and peak height
      were less than 1.1% and good linear relationship resulted. The developed method
      was applied to pharmaceutical formulations and biological fluids.

PMID- 17542057
TI  - Comparison of pharmacokinetics, efficacy and toxicity profile of gemcitabine
      using two different administration regimens in Chinese patients with non-small
      cell lung cancer.
AB  - OBJECTIVE: To conduct a randomized comparative trial of pharmacokinetics,
      efficacy and toxicity profile treatment with 1200 mg/m(2) gemcitabine using
      standard 30-min infusion or fixed dose rate (FDR) infusion [10 mg/(m(2) x min)]
      on days 1 and 8 plus carboplatin AUC (area under curve) 5 on day 1 in Chinese non
      small-cell cancer patients. Twelve patients were enrolled in this study. METHODS:
      Plasma gemcitabine concentrations were measured by ion-pair reversed phase high
      performance liquid chromatography. Antitumoral activity and toxicity of
      gemcitabine was assessed according to World Health Organization criteria.
      RESULTS: The obtained mean parameters, such as T(1/2) (elimination half time),
      AUC, and CL (clearance), were consistent with those reported in literature.
      Qualified response rate in our study was 33.3% for standard arm and 50% for FDR
      arm. Additional 50% and 33.3% patients contracted stable disease (SD) in standard
      arm and FDR arm, respectively. The predominant toxicity was hematologic, and
      patients in the standard infusion arm experienced consistently more hematologic
      toxicity. CONCLUSION: Pharmacokinetic and clinical data in this trial support the
      continued evaluation of the FDR infusion strategy with gemcitabine.

PMID- 17542058
TI  - Assignment of CCR7 gene to chicken chromosome 27 by radiation hybrid panel
      mapping.
AB  - The protein encoded by CC chemokine receptor 7 (CCR7) is a member of the G
      protein-coupled receptor family. This receptor was identified as a gene induced
      by the Epstein-Barr virus (EBV), and is thought to be a mediator of EBV effects
      on B lymphocytes. This receptor is expressed in various lymphoid tissues and
      activates B and T lymphocytes. It has been shown to control the migration of
      memory T cells to inflamed tissues, as well as stimulate dendritic cell
      maturation. To map the CCR7 gene in chicken chromosome, a 6 000 rads chicken
      hamster radiation hybrid panel (ChickRH6) was used. PCR of samples from ChickRH6
      revealed that the location of CCR7 gene is linked to the maker SEQ0347 (6 cR
      away) with LOD score of 16.6 and that the marker SEQ0347 is located on chromosome
      27 at 27 cR of RH (radiation hydrid) map. We compared the corresponding human
      mRNA sequence with the predicted coding sequence of chicken CCR7 gene, and found
      that the assembled contig shared a high percentage of similarity with that of the
      human gene.

PMID- 17542059
TI  - Nutrient composition, mineral content and the solubility of the proteins of palm
      weevil, Rhynchophorus phoenicis f. (Coleoptera: Curculionidae).
AB  - Adult (ADS) and larva stages of palm weevil Rhynchophorus phoenicis were analyzed
      for their nutritional potentials using proximate and mineral contents as indices.
      The early larva stage (ELS) contains the highest moisture content of 11.94% while
      ADS has the least value of 4.79%. The late larva stage (LLS) has the highest
      protein content of 10.51% while ADS contains 8.43%. Ash content is highest in ELS
      with a value of 2.37% and lowest in ADS with a value of 1.43%. ELS and LLS have
      the highest (22.14%) and lowest (17.22%) fibre contents respectively. The values
      of potassium, magnesium and iron in ELS were (455.00+/-21.21), (60.69+/-2.57) and
      (6.50+/-3.40) mg/kg while LLS recorded (457.50+/-10.61), (43.52+/-1.37) and
      (6.00+/-1.10) mg/kg and ADS recorded (372.50+/-24.75), (53.31+/-1.88) and
      (22.90+/-3.70) mg/kg. Chromium, phosphorus, nickel, calcium, lead, manganese and
      zinc were also detected. Copper was not detected in any of the samples. In all
      the developmental stages the protein solubilities were pH dependent with the
      minimum protein solubilities occurring at acidic pH while the maximum protein
      solubilities occurred at alkaline pH.

PMID- 17542060
TI  - Effects of chromium nanoparticle dosage on growth, body composition, serum
      hormones and tissue chromium in Sprague-Dawley rats.
AB  - This 6-week study was conducted to evaluate the effects of seven different levels
      of dietary chromium (Cr) (0, 75, 150, 300, 450, 600, and 1 200 ppb Cr) in the
      form of Cr nanoparticle (CrNano) on growth, body composition, serum hormones and
      tissue Cr in Sprague-Dawley (SD) rats. Seventy male SD rats (average initial body
      weight of (83.2+/-4.4) g) were randomly assigned to seven dietary treatments
      (n=10). At the end of the trial, body composition was assessed via dual energy X
      ray absorptiometry (DEXA). All rats were then sacrificed to collect samples of
      blood, organs and tissues for determination of serum hormones and tissue Cr
      contents. The results indicated that lean body mass was significantly increased
      (P<0.05) due to the addition of 300 and 450 ppb Cr from CrNano. Supplementation
      of 150, 300, 450, and 600 ppb Cr decreased (P<0.05) percent body fat
      significantly. Average daily gain was increased (P<0.05) by addition of 75, 150,
      and 300 ppb Cr and feed efficiency was increased (P<0.05) by supplementation of
      75, 300, and 450 ppb Cr. Addition of 300 and 450 ppb Cr decreased (P<0.05) the
      insulin level in serum greatly. Cr contents in liver and kidney were greatly
      increased (P<0.05) by the addition of Cr as CrNano in the dosage of from 150 ppb
      to 1 200 ppb. In addition, Supplementation of 300, 450, and 600 ppb Cr
      significantly increased (P<0.05) Cr content in the hind leg muscle. These results
      suggest that supplemental CrNano has beneficial effects on growth performance and
      body composition, and increases tissue Cr concentration in selected muscles.

PMID- 17542061
TI  - Improvement of the efficacy of influenza vaccination (H5N1) in chicken by using
      extract of Cochinchina momordica seed (ECMS).
AB  - Seeds of a Chinese traditional medicine plant, Cochinchina momordica were used in
      the present study for the improvement of influenza vaccine (H5N1) in chicken.
      Crude extraction from Cochinchina momordica seed (ECMS) was obtained by ethanol
      extraction method. In experiment No. 1, two weeks old chickens were immunized
      with influenza vaccine (H5N1) alone or combined with ECMS (5, 10, 20, 40 and 80
      microg/dose). Serum IgG antibody levels (by ELISA) as well as effects on daily
      weight gain were measured on 0, 7, 14 and 28th day after immunization. Results
      revealed that all ECMS groups numerically increased the antibody levels while 10
      and 20 microg/dose groups significantly (P<0.05) enhanced total IgG antibody on
      day 28, when compared with control. Average daily weight gain was also
      significantly higher in 20 microg/dose ECMS group. Adjuvant effect was also
      confirmed in experiment No. 2 when chickens were immunized with 20 microg/dose
      ECMS and antibody titer was measured through hemagglutination inhibition (HI). It
      is concluded that ECMS has potential to improve the immune responses and deserve
      further study as an adjuvant.

PMID- 17542062
TI  - Genetic analysis of fruit shape traits at different maturation stages in sponge
      gourd.
AB  - The fruit shape is important quantitative trait closely related to the fruit
      quality. However, the genetic model of fruit shapes has not been proposed.
      Therefore, in the present study, analysis of genetic effects for fruit shape
      traits (fruit length and fruit perimeter) in sponge gourd was conducted by
      employing a developmental genetic model including fruit direct effects and
      maternal effects. Analysis approaches of unconditional and conditional variances
      were applied to evaluate the genetic behavior of fruit shape traits at economical
      and physiological maturation times. The results of variance analysis indicated
      that fruit length and fruit perimeter were simultaneously affected by fruit
      direct genetic effects and maternal effects. Fruit direct genetic effects were
      relatively more important for fruit shape traits at whole developmental period.
      The gene expression was most active at the economical maturation stage (1
      approximately 12 d after flowering) for two shape traits, and the activation of
      gene was mostly due to direct dominance effects at physiological maturation stage
      (13 approximately 60 d after flowering). The coefficients due to different
      genetic effects, as well as the phenotypic correlation coefficients, varied
      significantly between fruit shape traits themselves at various maturation stages.
      The results showed that it was relatively easy to improve fruit shape traits for
      industrial purpose by carefully selecting the parents at economical maturation
      stage instead of that at physiological maturation stage.

PMID- 17542063
TI  - First record of Bursaphelenchus rainulfi on pine trees from eastern China and its
      phylogenetic relationship with intro-genus species.
AB  - Bursaphelenchus rainulfi isolated from dead pine trees in Zhejiang, China, is
      described and illustrated. It also provided some molecular characters of the
      Chinese population, including the PCR-RFLP and sequences of ITS region and D2-D3
      expansion region of the large subunit (LSU) rRNA gene. Both the morphological
      characters and ITS-RFLP patterns match with the original description. The
      phylogenetic trees based on the 13 sequences of D2-D3 expansion region of the LSU
      rRNA gene and ITS region of Bursaphelenchus species were constructed,
      respectively, with the results showing the similar clades. The phylogenetic
      relationship based on the molecular data is similar to that with morphological
      characters. This is the first report of the species on pine wood in eastern
      China.

PMID- 17542064
TI  - Chemical composition and antibacterial activity of Gongronema latifolium.
AB  - Chemical composition of Gongronema latifolium leaves was determined using
      standard methods. Aqueous and methanol G. latifolium extracts were tested against
      thirteen pathogenic bacterial isolates. Crude protein, lipid extract, ash, crude
      fibre and nitrogen free extractives obtained are: 27.2%, 6.07%, 11.6%, 10.8% and
      44.3% dry matter respectively. Potassium, sodium, calcium, phosphorus and cobalt
      contents are 332, 110, 115, 125 and 116 mg/kg respectively. Dominant essential
      amino acids are leucine, valine and phenylalanine. Aspartic acid, glutamic acid
      and glycine are 13.8%, 11.9% and 10.3% respectively of total amino acid.
      Saturated and unsaturated fatty acids are 50.2% and 39.4% of the oil
      respectively. Palmitic acid makes up 36% of the total fatty acid. Extracts show
      no activity against E. faecalis, Y. enterolytica, E. aerogenes, B. cereus and E.
      agglomerans. Methanol extracts were active against S. enteritidis, S. cholerasius
      ser typhimurium and P. aeruginosa (minimum inhibitory concentration (MIC) 1 mg;
      zone of growth inhibition 7, 6.5 and 7 mm respectively). Aqueous extracts show
      activity against E. coli (MIC 5 mg) and P. aeruginosa (MIC 1 mg) while methanol
      extracts are active against P. aeruginosa and L. monocytogenes. G. latifolium has
      potential food and antibacterial uses.

PMID- 17542065
TI  - Scaling behavior of nucleotide cluster in DNA sequences.
AB  - In this paper we study the scaling behavior of nucleotide cluster in 11
      chromosomes of Encephalitozoon cuniculi Genome. The statistical distribution of
      nucleotide clusters for 11 chromosomes is characterized by the scaling behavior
      of P(S) proportional, variant e(-alphaS), where S represents nucleotide cluster
      size. The cluster-size distribution P(S(1)+S(2)) with the total size of
      sequential C-G cluster and A-T cluster S(1)+S(2) were also studied. P(S(1)+S(2))
      follows exponential decay. There does not exist the case of large C-G cluster
      following large A-T cluster or large A-T cluster following large C-G cluster. We
      also discuss the relatively random walk length function L(n) and the local
      compositional complexity of nucleotide sequences based on a new model. These
      investigations may provide some insight into nucleotide cluster of DNA sequence.

PMID- 17542066
TI  - Studies on optimization of nitrogen sources for astaxanthin production by Phaffia
      rhodozyma.
AB  - Fermentation of Phaffia rhodozyma is a major method for producing astaxanthin, an
      important pigment with industrial and pharmaceutical application. To improve
      astaxanthin productivity, single factor and mixture design experiments were used
      to investigate the effects of nitrogen source on Phaffia rhodozyma cultivation
      and astaxanthin production. Results of single factor experiments showed nitrogen
      source could significantly affect P. rhodozyma cultivation with respect to carbon
      source utilization, yeast growth and astaxanthin accumulation. Further studies of
      mixture design experiments using (NH(4))(2)SO(4), KNO(3) and beef extract as
      nitrogen sources indicated that the proportion of three nitrogen sources was very
      important to astaxanthin production. Validation experiments showed that the
      optimal nitrogen source was composed of 0.28 g/L (NH(4))(2)SO(4), 0.49 g/L KNO(3)
      and 1.19 g/L beef extract. The kinetic characteristics of batch cultivation were
      investigated in a 5-L pH-stat fermentor. The maximum amount of biomass and
      highest astaxanthin yield in terms of volume and in terms of biomass were 7.71
      mg/L and 1.00 mg/g, respectively.

PMID- 17542067
TI  - Effect of cultivating conditions on alpha-galactosidase production by a novel
      Aspergillus foetidus ZU-G1 strain in solid-state fermentation.
AB  - The work is intended to achieve optimum culture conditions of alpha-galactosidase
      production by a mutant strain Aspergillus foetidus ZU-G1 in solid-state
      fermentation (SSF). Certain fermentation parameters involving moisture content,
      incubation temperature, cultivation period of seed, inoculum volume, initial pH
      value, layers of pledget, load size of medium and period of cultivation were
      investigated separately. The optimal cultivating conditions of alpha
      galactosidase production in SSF were 60% initial moisture of medium, 28 degrees C
      incubation temperature, 18 h cultivation period of seed, 10% inoculum volume, 5.0
      approximately 6.0 initial pH of medium, 6 layers of pledget and 10 g dry matter
      loadage. Under the optimized cultivation conditions, the maximum alpha
      galactosidase production was 2 037.51 U/g dry matter near the 144th hour of
      fermentation.

PMID- 17542068
TI  - Uvulitis.

PMID- 17542069
TI  - Cervical screening.

PMID- 17542070
TI  - HSV therapy and HIV-1 reduction.

PMID- 17542071
TI  - Perioperative stroke.

PMID- 17542072
TI  - Perioperative stroke.

PMID- 17542073
TI  - Case 3-2007: a boy with respiratory insufficiency.

PMID- 17542074
TI  - Case 3-2007: a boy with respiratory insufficiency.

PMID- 17542076
TI  - Abstracts of the 11th International Congress of Parkinson's Disease and Movement
      Disorders, June 3-7, 2007, Istanbul, Turkey.

PMID- 17542075
TI  - Proceedings and abstracts of the 3rd World Congress on Abdominal Compartment
      Syndrome, Antwerp, Belgium, March 22-24, 2007.

PMID- 17542077
TI  - Master author and keywords indexes, volumes 529-553, 2006.

PMID- 17542078
TI  - Alzheimer's and Parkinson's Diseases: Progress and New Perspectives. Abstracts of
      the 8th International Conference AD/PD, Salzburg, Austria, March 14-18, 2007.
      Abstracts.

PMID- 17542081
TI  - Nurses occupational health and safety, rehabilitation and compensation rights at
      risk.

PMID- 17542084
TI  - [Regional meeting of the Japan Radiological Society. 2004-2005. Abstracts].

PMID- 17542083
TI  - [The 19th spring meeting of the Japanese Society of Allergology. Yokohama, Japan.
      June 10-12, 2007. Abstracts].

PMID- 17542085
TI  - [The 48th annual meeting of the Japanese Society of Neurology. Nagoya, Japan. May
      16-18, 2007. Abstracts].

PMID- 17542086
TI  - [Deficient intensive care capacity and physicians' responsibility].

PMID- 17542087
TI  - [Children with cochlear implants: language development].

PMID- 17542088
TI  - Object or subject? The paradox of "youth" in Turkey.

PMID- 17542089
TI  - [Invasive radiology and life-threatening hemorrhage].

PMID- 17542090
TI  - Water, geopolitics and state building: the case of Israel.

PMID- 17542091
TI  - Meeting of the International Task Force for Disease Eradication--11 January 2007.

PMID- 17542092
TI  - Performance of acute flaccid paralysis (AFP) surveillance and incidence of
      poliomyelitis, 2005-2006 (data received in WHO headquarters as of 22 May 2007).

PMID- 17542093
TI  - Stop TB Partnership has provided treatments for 10 million people in 6 years.

PMID- 17542094
TI  - Making the modern world.

PMID- 17542095
TI  - Fools are everywhere.

PMID- 17542096
TI  - The history of deforestation.

PMID- 17542097
TI  - Russian revisionism: Holocaust denial and the new nationalist historiography.

PMID- 17542098
TI  - Traffic deaths and injuries: an issue we can battle.

PMID- 17542099
TI  - The effect of prescription drug insurance on utilization and health among the
      elderly.

PMID- 17542100
TI  - Does watching television trigger autism?

PMID- 17542101
TI  - High-performance health plan networks: early experiences.
AB  - Health plans have introduced high-performance networks to encourage use of
      network providers--predominantly physician specialists--deemed high performing on
      efficiency and quality measures. Early adopters of these networks are large
      national employers, and, while other employers are interested, actual adoption
      has lagged, according to a study by the Center for Studying Health System Change
      (HSC). Enrollment in products using high-performance networks is limited, and
      objective evidence on the impact on service use, costs and quality is lacking.
      Early lessons learned indicate the need for effective communication between plans
      and providers, use of both efficiency and quality measures, industry standards of
      provider performance, and employer support.

PMID- 17542102
TI  - Medicare finances: findings of the 2007 Trustees report.
AB  - Each year Medicare's Board of Trustees issues a report that describes the
      financial condition of the Medicare program in the near term and over the next 75
      years. Similar to recent trustees reports, the 2007 report projects that
      Medicare's Hospital Insurance Trust Fund will be depleted in 2019, at which time
      scheduled income will cover 79 percent of expenditures. For the first time, the
      trustees have issued a "Medicare funding warning," which means that more than 45
      percent of Medicare will be financed by general (non-dedicated) revenues within
      the next seven years. Looking at these projections, some observers contend that
      Medicare must be fundamentally restructured in order to put the program--and the
      overall federal budget--on a sound fiscal course. Others point out that Medicare
      spending has grown at about the same rate as spending for private health
      insurance and argue that it is impossible to limit spending on Medicare without
      also slowing the growth of private health care costs or abandoning equal access
      to care for the aged and disabled.

PMID- 17542103
TI  - Universal health care.

PMID- 17542104
TI  - Postpartum depression: worse than baby blues.

PMID- 17542106
TI  - Trading places: Real Choice Systems Change grants and the movement to community
      based long-term care supports.
AB  - The Real Choice Systems Change grant program was created to help states transform
      their long-term care service systems from ones that rely on institutions to ones
      that are more community-based. The grants are intended to help states develop the
      infrastructure needed for seniors and individuals with disabilities to live in
      integrated community settings. This issue brief provides information about
      Systems Change grants and the kinds of activities state Medicaid agencies have
      undertaken to transform their institutionally based systems. In addition, this
      paper reports on some of the qualitative and quantitative responses to the
      changes. This brief also raises critical policy questions related to public
      spending for long-term care in different settings that might be considered in
      tandem with future grant funding decisions.

PMID- 17542109
TI  - Quantifiable impact on poverty in Trinidad And Tobago of the Uruguay Round
      Agreement On Agriculture.
AB  - BACKGROUND: The agreement on agriculture and the World Trade Organization were
      major outcomes of the 1986-1994 Uruguay Round (UR) negotiations within the
      General Agreement on Tariffs and Trade (GATT). The measures under the UR were
      predicted to increase poverty in developing countries, a serious cause for
      concern since poverty alleviation is a major goal of developing countries. Thus
      this paper simulated the impact on poverty of the UR for a net food importing
      country, Trinidad and Tobago. OBJECTIVE: The objectives of the study were to
      determine the changes in poverty levels in Trinidad and Tobago that we expected
      would result from changes in the price levels of food commodities after the
      removal of trade protection following the UR, and to examine recent trends in
      poverty in Trinidad and Tobago and the prices of major agricultural exports from
      the United States, its principal trading partner. METHODS: A regression model
      (poverty model) was used to determine the relationship between poverty levels and
      the prices of sensitive imported food commodities (SIFCs) and other key economic
      variables. Impact models were used to project changes in world market prices of
      the SIFCs due to the UR, and these price changes were used to predict changes in
      poverty in Trinidad and Tobago. RESULTS: The results showed a positive elasticity
      between poverty and the prices of SIFCs. The study also predicted that the
      average projected increase in price levels of the SIFCs of less than 9% by the
      year 2000 would cause an increase in poverty in Trinidad and Tobago of less than
      4%. CONCLUSIONS: There has been, in fact, a small decline in poverty in Trinidad
      and Tobago since 1996. The prices of major agricultural exports from the United
      States have also been falling since 1995. Thus, so far the UR has had no
      perceptible effects in increasing the prices of food exports from the United
      States. Also, so far the UR has had no perceptible effect on the poverty level in
      Trinidad and Tobago.

PMID- 17542110
TI  - Impact of a multiple-micronutrient food supplement on the nutritional status of
      schoolchildren.
AB  - BACKGROUND: . Multiple-micronutrient deficiencies exist in many developing
      nations. A system to deliver multiple micronutrients effectively would be of
      value in these countries. OBJECTIVE: . To evaluate the delivery of multiple
      micronutrients through the food route. The goal was to test the stability of the
      supplement during cooking and storage and then to test its bioefficacy and
      bioavailability in residential schoolchildren 5 to 15 years of age. METHODS: A
      pre- and post-test design was used to study children 5 to 15 years of age, with
      an experimental and a control group. The experimental group (n=211) consisted of
      children from two residential schools, and the control group (n=202) consisted of
      children from three residential schools. The experimental group received a
      micronutrient supplement containing vitamin A, vitamin B2, vitamin B6 vitamin
      B12, folic acid, niacin, calcium pantothenate, vitamin C, vitamin E, iron,
      lysine, and calcium daily for 9 months. There was no nutritional intervention in
      the control group. Children in the experimental and control groups were matched
      by socioeconomic status, age, and eating habits at baseline. All of the children
      in the experimental and control schools were dewormed at baseline, after 4
      months, and at the endpoint. Biochemical measurements (hemoglobin, serum vitamin
      A, serum vitamin E, serum vitamin B12, and serum folic acid) were measured at
      baseline, after 4 months, and at the endpoint (after 9 months). The heights and
      weights of the children were also measured at baseline and endpoint. Serum
      vitamins A and E were measured in a subsample of 50% and vitamin B12 and serum
      folic acid measured in a subsample of 25% of the children. RESULTS: In the
      experimental group, the mean gains in hemoglobin, serum vitamin A, serum vitamin
      E, serum vitamin B12, and serum folic acid over 9 months were 0.393 g/dL, 6.0375
      microg/dL, 1037.45 microg/dL, 687.604 pg/mL, and 1.864 ng/mL, respectively. In
      the control group, the mean losses in hemoglobin and serum vitamin A over 9
      months were 0.9556 g/dL and 10.0641 microg/dL, respectively, and the mean gains
      in serum vitamin E, vitamin B12, and folic acid were 903.52 microg/dL, 233.283
      pg/mL, and 0.0279 ng/mL. The mean gain in all biochemical measurements was
      significantly higher (p < .05) in the experimental group than in the control
      group. CONCLUSIONS: Vitamin A, vitamin E, vitamin B12, folic acid, and iron are
      bioavailable from the multiple-micronutrient food supplement used in this study.
      This method of micronutrient delivery has been beneficial. We believe the study
      intervention was beneficial because of small doses of the micronutrients added
      but delivered many times through meals throughout the day, over a period of 9
      months.

PMID- 17542111
TI  - Contribution of a novel high-density micronutrient condiment (HDMC) to nutrient
      adequacy of home-prepared Guatemalan dishes.
AB  - BACKGROUND: The diet of low-income Guatemalan populations is mostly plant-based,
      deficient in some vitamins and minerals, and rich in antinutritional compounds
      that reduce the bioavailability of several micronutrients. Objective. To describe
      the manner in which low-income Guatemalan women in rural and urban settings would
      prepare dishes for main meals using a high-density multimicronutrient condiment
      (HDMC) and to compare the nutrient density and contribution to the recommended
      dietary allowance (RDA) of the dishes with and without added HDMC. METHODS: A
      sample of 30 women, 15 each from rural and urban households, were enrolled. The
      women were given 20 g of the HDMC and asked to prepare a dish at home, serve it
      to their families at a time of their own choosing, record the recipe and the
      amount of condiment added, and report these facts to an interviewer on the
      following day. The nutrient content of each dish was calculated from food
      composition table values for raw, whole ingredients and the package label values
      for the HDMC. RESULTS: For all dishes combined, the HDMC provided on average 78%
      of the total vitamins. The proportion of the total vitamins provided by the HDMC
      varied greatly among different dishes. Typically a single serving of a dish
      without added HDMC provided less than half of the RDA (vitamin B12 and folate)
      for children and adult women. The midday meal is the most important meal of the
      day and should provide at least half of the RDA of all essential nutrients. With
      the HDMC added, the dishes on average provided 2 to 10 times the RDA for
      nutrients such as vitamins B6 and C and niacin in the reference children, and
      just satisfied the RDA intake for corresponding nutrients in adult women.
      CONCLUSIONS: The proportion of the RDAs of micronutrients provided by this novel,
      micronutrient-rich condiment varies over a wide range, depending on
      idiosyncrasies of recipe ingredients, amounts of condiment added, individuals
      served, and age- and physiology-dependent requirements. HDMCs could provide an
      efficient way to deliver essential micronutrients to vulnerable populations.

PMID- 17542112
TI  - Effectiveness of intermittent iron treatment of two- to six-year-old Jordanian
      children with iron-deficiency anemia.
AB  - BACKGROUND: Iron deficiency is a common nutritional problem in young children
      among vulnerable populations in Jordan. Several studies have shown the
      effectiveness of intermittent iron supplementation in improving iron status. Such
      a study has not been carried out in 2- to-6-year-old Jordanian children diagnosed
      with iron deficiency anemia in a clinical setting. OBJECTIVE: To study the
      effectiveness of intermittent versus daily iron treatment in a clinical setting
      in 2- to 6-year-old Jordanian children with iron-deficiency anemia. METHODS:
      About 4400 children aged 2 to 6 years who visited Prince Hashim Military Hospital
      in Zarqa, Jordan, from August 2000 to June 2001 were screened for age, general
      health, and birthweight. About 10% of these children were screened for anemia,
      using complete blood count (defined as a hemoglobin level < or = 10.5 g/dL, and a
      mean corpuscular volume < or =75 ft). Anemic children underwent further screening
      for iron deficiency, defined as serum ferritin level < or =12 microg/L. Children
      with iron-deficiency anemia, as indicated by hemoglobin < or = 10.5 g/dL, mean
      corpuscular volume < or =75 fL, and serum ferritin < or =12 microg/L, or as
      indicated by mean corpuscular volume < or =75 fL and hemoglobin < or = 10.5 g/dL,
      were enrolled in the study after informed oral consent by their parents. Study
      children (n=134) were assigned randomly to one of three groups. Subjects in group
      1 (n=45), group 2 (n=45), and group 3 (n=44) received iron treatment daily,
      weekly, and twice weekly, respectively. Out of 134 children recruited for the
      study, only 63 (39 boys and 24 girls) completed the 3-month treatment period. All
      of the children received medicinal iron drops at a dosage of 5 mg elemental iron
      as ferrous sulfate per kilogram of body weight. The parents also received
      nutritional counseling. RESULTS: At the end of treatment, hemoglobin, serum
      ferritin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin, and
      mean corpuscular hemoglobin concentration increased significantly in all groups
      with no significant differences between groups. The increases in hemoglobin in
      groups 1, 2, and 3 were 2.47 +/- 0.17, 2.12 +/- 0.18, and 2.18 +/- 0.18 g/dL,
      respectively. Measurements of final serum ferritin concentration were available
      for only 12, 12, and 10 children in groups 1, 2, and 3, respectively. In all
      children who completed the study, except for one in group 1, hemoglobin, mean
      corpuscular volume, and serum ferritin reached normal values in response to iron
      treatment. CONCLUSIONS: Weekly and twice-weekly iron therapy with 5 mg elemental
      iron as ferrous sulfate per kilogram of body weight accompanied by nutritional
      counseling was as effective as daily iron therapy in correcting iron-deficiency
      anemia in 2- to 6-year-old children under the clinical conditions of this study.

PMID- 17542113
TI  - Maternal nutritional status in pastoral versus farming communities of West Pokot,
      Kenya: differences in iron and vitamin A status and body composition.
AB  - BACKGROUND: Underweight and micronutrient deficiencies are sequelae of the
      prevailing harsh living and economic conditions of women in sub-Saharan Africa.
      There are few data describing maternal nutritional status in these resource-poor
      settings. Provision of more effective modes of intervention requires that public
      health and nutrition policy at both the national and the multisectoral levels be
      based on community-specific nutritional and behavioral practices. OBJECTIVE: This
      longitudinal study investigated maternal micronutrient status in two remote,
      semiarid, rural communities that are ethnically similar but have distinctly
      different pastoral and farming lifestyles. We looked at differences in iron
      stores, vitamin A levels, and body composition of women in the third trimester of
      pregnancy and again at 4 months postpartum. METHODS: Complete data were collected
      from 113 pastoral and 110 farming Pokot women. Anthropometric measurements were
      taken, and serum ferritin and retinol levels were measured. Infants were weighed
      within 7 days of birth. RESULTS: Women from the farming community had
      significantly (p < .05) lower hemoglobin concentrations than women from the
      pastoral community during the third trimester of pregnancy. Pastoral women had
      significantly higher serum ferritin concentrations than farming women during the
      third trimester of pregnancy (p <.05) and at 4 months postpartum. There were no
      significant differences between pastoral and farming women in the percentage of
      women with serum retinol levels < 0.70 micromol/L during the third trimester of
      pregnancy (27.9% [34/113] and 24.2% [31/110], respectively) and at 4 months
      postpartum (29.2% [33/113] and 30.9% [34/110]) In the farming community, mean
      infant birthweight was significantly lower (p <. 01) than in the pastoral
      community and a significantly higher (p < .05) proportion of newborns weighed
      less than 2.5 kg. At 4 months postpartum, the percentage of body fat was
      significantly lower in pastoral women than in farming women. CONCLUSIONS: Women
      from the farming community in West Pokot, Kenya, have lower iron stores during
      the third trimester of pregnancy than women in the pastoral community. In
      addition, the mean weight of their newborn infants is lower than that of infants
      in the pastoral community. These findings may be associated with differences in
      living conditions, which are usually harsher in farming than in pastoral
      communities.

PMID- 17542114
TI  - Constraints on good child-care practices and nutritional status in urban Dar-es
      Salaam, Tanzania.
AB  - BACKGROUND: Care is increasingly being recognized as a crucial input to child
      health and nutrition, along with food security, availability of health services,
      and a healthy environment. Although significant gains have been made in the fight
      against malnutrition in Tanzania, the nutritional status of preschool children in
      urban areas is not improving. OBJECTIVE: To assess child-care practices and the
      nutritional status of infants and young children with the aim of improvingfeeding
      practices and child nutritional status. METHODS: A cross-sectional study was
      undertaken in urban Dar-es-Salaam, Tanzania. The study involved 100 randomly
      selected mothers of children 6 to 24 months old from households in Ilala
      Municipality, one of the three municipalities that constitute the Dar-es-Salaam
      City Council. Data were collected by a structured questionnaire, spot-check
      observations, and anthropometric measurements. RESULTS: The prevalence rates of
      stunting, underweight, wasting, and morbidity were 43%, 22%, 3%, and 80%,
      respectively. The prevalence of exclusive breastfeeding was very low (9%), and
      most stunted children (88%) were not exclusively breastfed for the first 6
      months. The mean age at which complementary foods and fluids were introduced was
      3.26 +/- 1.12 months (range, 1 to 5 months). The fluids given were mainly water
      and thin cereal-based porridge. More than half of the households practiced good
      hygiene. Most of the psychosocial practices (e.g., caregiver's attention,
      affection, and involvement in child feeding, hygiene, health care, and training)
      were performed by mothers, except for cooking and feeding the children and child
      training, which were done mostly by alternative caregivers. Nearly half of the
      mothers (44%) worked out of the home. The mean number of working hours per day
      was long (10.32 +/- 2.13), necessitating the use of alternative caregivers. A
      negative correlation was found between height-for-age z-scores and the number of
      hours mothers worked outside the home. CONCLUSIONS: The prevalence rates of
      chronic malnutrition and morbidity are high, and child-feeding practices are
      inadequate in this urban population. Maternal employment and educational
      characteristics constrain good child-care practices, and alternative caregivers
      are taking a more important role in child care as mothers join the work force. We
      recommend that formative research be conducted to study the actual practices of
      caregivers in order to form the basis for a child-care education program. There
      is also a need to strengthen national health system support for improved child
      feeding.

PMID- 17542115
TI  - Milk thickeners do not influence anthropometric indices in childhood.
AB  - BACKGROUND: Pediatric obesity is an important risk factor for chronic diseases in
      adulthood. Some infant feeding practices may contribute to childhood obesity.
      OBJECTIVE: To investigate whether the introduction of milk thickeners to bottle
      fed infants between 3 and 6 months of age was associated with higher
      anthropometric measurements and indices at 1 and 4 years of age. METHODS: A
      population-based birth cohort study was conducted in 1993 in the urban area of
      Pelotas, Brazil. Information was obtained at birth, at 1, 3, 6, and 12 months,
      and at 4 years. Data were analyzed from the 596 children for whom information was
      available from all follow-up visits. The exposure of interest was the use of milk
      thickener (flour added to cow's milk) between the third and sixth months of life.
      The outcomes investigated were weight and length/height and the anthropometric
      indices weight-for-age, length/height-for-age, and weight-for-length/height z
      scores at 1 and 4 years. RESULTS: The prevalence of use of milk thickener at any
      time between the third and sixth months was 44.6%. In the adjusted analysis,
      children who received milk thickener were, on average, 160 g heavier and 0.5 cm
      longer at I year than those who did not receive it. Weight-for-age and length-for
      age z-scores were positively associated with use of milk thickener. No
      association was observed between this feeding practice and weight-for-length z
      score. In the adjusted analysis, no effect of use of milk thickener on any of the
      anthropometric outcomes studied was observed at 4 years. CONCLUSIONS: No
      association was found between the use of milk thickeners and weight-for
      length/height z-scores in the first and fourth years of life. Future studies in
      other contexts would be helpful to further test this hypothesis.

PMID- 17542116
TI  - Vitamin A stability in salt triple fortified with iodine, iron, and vitamin A.
AB  - BACKGROUND: Dietary micronutrient deficiencies, which lead to diseases such as
      iodine deficiency disorders, iron-deficiency anemia, and vitamin A deficiency,
      are serious public health problems in the developing world. Fortifying salt with
      iodine, iron, and vitamin A is an attractive approach to simultaneously reduce
      the deficiencies of these three micronutrients in the diet. OBJECTIVE: To explore
      the technical feasibility of producing triple-fortified salt fortified with
      iodine, iron, and vitamin A that would be stable under the climatic conditions of
      developing countries (i.e., high temperature and high humidity). METHODS: Triple
      fortified salt was obtained by granulation and encapsulation of commercially
      produced vitamin A products, iodine, and iron compounds. Vitamin A retention was
      determined in the presence of five iron and two iodine compounds, in different
      combinations, under three different storage conditions. The influence of
      commercial stabilization techniques for the vitamin A palmitate source used
      (spray-dried or dissolved in oil), and the type of binder used for granulation on
      vitamin A retention in triple-fortified salt was studied. The influence of
      temperature, humidity, and chemical interactions on vitamin A stability in triple
      fortified salt was also investigated. RESULTS: The most stable formulation
      retained 77.73% of vitamin A after 2 months of storage at 40 degrees C, 60%
      relative humidity, and 95% under ambient conditions. CONCLUSIONS: The results
      indicate that the production of a stable triple-fortified salt is technically
      feasible.

PMID- 17542117
TI  - Nutrition education alone improves dietary practices but not hematologic indices
      of adolescent girls in Iran.
AB  - BACKGROUND: Iron-deficiency anemia is the most prevalent nutritional deficiency
      worldwide. Iron-deficiency anemia has particular negative consequences on women
      in their childbearing years, and its prevention is a high priority in most health
      systems. OBJECTIVE: This interventional study assessed the effect of nutrition
      education on hematologic indices, iron status, nutritional knowledge, and
      nutritional practices of high-school girls in Iran. METHODS: Sixty healthy 16- to
      18-year-old girls were randomly selected from two high schools in the city of
      Ahvaz and divided into two equally matched groups, one that received nutrition
      education, and one that did not. The education group received instruction in face
      to-face sessions, group discussions, and pamphlets for 2 months. The control
      group did not receive any information during the study. Hematologic tests,
      corpuscular indices, and serum ferritin levels were measured at baseline and
      after 2 months. Food-frequency questionnaires were administered and histories
      taken, clinical signs of nutritional deficiencies observed, anthropometric
      measurements taken, nutritional knowledge tested, practices determined, and
      lifestyle questionnaires administered to all subjects. RESULTS: There were no
      statistically significant differences in any baseline characteristics between the
      two groups. Scores for nutritional knowledge and practices of the education group
      were significantly higher after two months compared with the baseline (31.4 +/- 6
      vs. 24.3 +/- 5.9 points, p < .001, and 31.2 +/- 5 vs. 28.4 +/- 5.7 points, p <
      .05, respectively). The scores in the control group showed no significant changes
      from baseline to 2 months. Mean corpuscular volume values were elevated in the
      education group (p < .001) but not in the control group. However, in the control
      group, serum ferritin concentrations showed about a 17% drop at the end of the
      study (p < .004). There were no changes in other hematologic, lifestyle,
      clinical, or anthropometric data compared with baseline after completion of the
      study in both groups. CONCLUSION: These findings indicate that nutritional
      education can improve knowledge of healthy nutrition and lifestyle choices.
      Focused nutritional education using available resources and correcting current
      dietary habits in a vulnerable group of young women may result in dietary changes
      that can ultimately improve iron intake.

PMID- 17542118
TI  - Quality protein maize.

PMID- 17542119
TI  - Mysore Declaration: capacity strengthening in nutrition.

PMID- 17542120
TI  - The construction of the European higher education space.

PMID- 17542121
TI  - [Aesthetic procedures: client's perception regarding the information given for
      the decision making process].
AB  - This research verified client's perception regarding the information given and
      freedom of choice for the decision making process related to aesthetic
      procedures. It was carried out with a sample of 44 clients of the clinic where
      the study was conducted. Data collection was based on 28 propositions classified
      in three categories: Information, Competence and Freedom, and two scales to
      measure client's perception concerning the elucidation of the information
      provided and freedom of choice. Most clients were married women, with a
      University degree, professional background classified in levels III, IV and V,
      monthly income above 30 minimum wages, and in the age group from 41 to 50 years
      old. There was a predominance of clinical treatment compared to surgical ones,
      and superiority on the average score given to Competence compared to Information
      provided and Freedom. Based on the scales concerning client's perception, we
      concluded that in general clients felt they were fully informed and were free to
      choose the procedures that suited them best.

PMID- 17542122
TI  - [Burn experiences from the patient's perspective].
AB  - This study was aimed at identifying situations experienced by burned patients
      which they perceived as significant during hospitalization, as well as
      identifying the feelings and consequences that resulted from the reported
      situations. The Critical Incident Technique was used for data collection, based
      on descriptions of facts which patients had previously observed and experienced
      as referred to by their memories. Thirty patients were submitted to semi
      structured interviews. The situations identified as significant were categorized
      as follows: feeling pain and having to subject themselves to procedures; having a
      new experience, receiving family and team support or not; and knowing the
      situation of other burned persons. The feelings and behaviors that were mentioned
      were anxiety and fear, and suffering and comfort when seeing others whose
      conditions are worse. From the perspective of patients, the consequences of going
      through this experience were changes in values, lifestyle, social role and
      health.

PMID- 17542123
TI  - ["Do this, do that, but I'm falling down..."--understanding Crohn's disease].
AB  - This qualitative study was developed as an effort to understand the meaning and
      the impact of Chron's Disease on the carrier's life, opting for Life Oral History
      as the methodological reference and having as a base Hippocrates' monist
      philosophical school, for which the medical practice focuses on the sick person
      in his/her totality, taking into consideration his/her temperament and
      background. The therapeutics must reestablish the person's harmony with his/her
      environment and with himself/ herself. It is an integrative, dynamic medicine
      that corresponds to the beginnings of psychosomatic medicine. The studies on
      Chron's Disease, through psychosomatic understanding, made possible to analyze
      the symptoms not as alien bodies to be eradicated, but as messengers of an appeal
      to be understood. Through them, the person's history can be recovered, which
      makes possible the development to more advanced levels of understanding if it is
      experienced and analyzed consciously.

PMID- 17542124
TI  - [Culture permeating the feelings and the reactions in the face of pain].
AB  - This study describes the perception of pain and the meanings it has for adults
      who use the Brazilian public health system, the Sistema Unico de Saude (SUS). The
      sample was comprised of 60 patients who sought the service in the period. This is
      a descriptive-explanatory research whose data were collected through semi
      structured interviews and evaluated qualitatively. The emerging themes were
      grouped into categories. It was observed that "the meaning of pain" revealed the
      preponderance of the comprehension of pain as a physical matter. It also showed
      that pain is related to emotional, sentimental, religious and human circumstances
      as well. "The reaction of men and women in the face of pain" is perceived
      differently according to the gender. In questions such as "How do you feel when
      you are in pain?" the answers varied between affective, cognitive and behavioral.

PMID- 17542125
TI  - [Life-death duality in the experience of metastasis patients].
AB  - The new millennium brings along a new reality to Brazil: population aging, and
      with it an increase in cases of chronic diseases, among them cancer. With the
      purpose of understanding how oncological patients under chemotherapeutic
      treatment due to the metastasis experience the possibility of dying, seven
      interviews with patients from an oncology clinic were carried out in a small town
      in the state of Parana. In order to analyze these interviews, ideas from Martin
      Heidegger's philosophical reference were used. From this analysis, death showed
      itself in different ways: implicitly; as a natural phenomenon, experienced in an
      impersonal way through someone else's death; as a phenomenon that permeates life.
      The it-happens-to-the-other condition made possible to unveil death through
      words, actions and looks, which at the same time shelter and denounce; and
      through the relation with the health professionals through caring forms almost
      always unauthentic.

PMID- 17542126
TI  - [Therapeutic practices among elders in Porto Alegre: a qualitative approach].
AB  - This study had as its main objective to know, comprehend and analyze the use of
      therapeutic practices among elders who live in urban areas. With a qualitative
      approach, this research was carried out in the eastern part of the city of Porto
      Alegre, State of Rio Grande do Sul. It processed the socio-demographic
      characterization of 24 elders randomly chosen and the analysis of the information
      collected from them regarding the use of therapeutic practices. The elders
      interviewed were in their majority female, 68-years old in average, with four
      years of schooling. The main therapeutic practice mentioned by the interviewees
      was self-medication. Another therapeutic practice that was mentioned is the visit
      to a health professional. The study considers that through the analysis and
      critical discussion of the theme it is possible to provide subsidies for the
      qualification of professionals in the field of Health education and of nursing
      work in general, thus favoring the care and self-care processes among elders.

PMID- 17542127
TI  - [The meaning attributed to 'being old' by workers of long-term care nursing
      institutions].
AB  - This is a descriptive and explorative study with a quantitative approach aimed at
      identifying the meaning of 'being old' according to 50 health-care workers
      responsible for direct nursing care to elderly residents in nursing homes. Data
      was obtained by means of the Portuguese version of the 'Semantic Differential
      Scale' validated in Brazil. Subjects were predominantly nursing assistants and
      'general services' workers. The majority of them conferred to the elderly the
      adjectives beautiful, tender, sweet, wise, interesting, with sense of
      opportunity, humble and resigned. The attributes destructive, insecure, critic
      and intrusive were also cited. Most subjects selected adjectives that, in spite
      of being positive, are also related with docility and passivity.

PMID- 17542128
TI  - [Working with families within the Family Health Program: nurse's practice in
      Maringa - Parana].
AB  - The Family Health Program (Programa de Saude da Familia, PSF) was conceived with
      the aim of fully assisting families in their social space, which requires a new
      professional posture. This work had the purpose of investigating the practices
      with families of the nurses that work in the PSF in the city of Maringa, in the
      State of Parana. An exploratory descriptive study with qualitative approach was
      carried out using for data collecting interviews, observation and documental
      analysis. Data were analyzed according to Bardin theoretical referential. The
      results revealed three categories in the Nursing practice with families:
      activities with individuals, activities in the community and activities at family
      homes. It was concluded that in spite of the fact that nurses consider families
      in a home context through home visits, data collecting and health education, they
      still focus on the disease and on the individual. Such approach has not
      stimulated the participation and autonomy of the families regarding care and the
      service.

PMID- 17542129
TI  - [Readmission to a psychiatric hospital: the comprehension of the health/illness
      process through the experience of daily life].
AB  - This study is part of a research that aimed at identifying the daily life of
      people with mental disruptions who are re-admitted to psychiatric hospitals. It
      was possible to pinpoint that these individuals express several conceptions of
      the health/mental illness process and that they also distinguish the kinds of
      treatment they go through. As far as methodology is concerned the study used the
      qualitative approach based on Agnes Heller's concept of daily life. The
      interviews with patients and their relatives were submitted to speech analysis,
      which showed, among other results, that relatives have developed new tools and
      possibilities in order to understand the patients' mental state and provide them
      with the necessary assistance.

PMID- 17542130
TI  - [The working process in labor care in Londrina-PR].
AB  - In this study, delivery care in the city of Londrina, State of Parana, was
      investigated under the focus of health professionals' decisions to prescribe
      procedures such as fasting, enema and trichotomy. The theoretical referential was
      historical and dialectical materialism. The data survey was carried out in 2000
      in five institutions and included individual interviews with ten obstetricians,
      eight nurses and one midwife. The interviews were interpreted using the speech
      analysis and then the thematic phrases were extracted. It was possible to
      identify the working process and its constitutive elements. The physician is the
      only one with decision power. Such power is reinforced by the following
      instruments identified in the study: medical prescriptions, nursing staff's work
      and the place where it is practiced--the hospital. The knowledge that supports
      this practice is the clinical model, represented by non-individualized
      interventions that focus more on the agents' needs than on their object's (the
      parturient).

PMID- 17542131
TI  - [The direct cost of the cardiopulmonary resuscitation training program in a
      university hospital].
AB  - This study was aimed at mapping the process of shared training in cardiopulmonary
      resuscitation for technicians and assistant nurses of the Intensive Care and Semi
      Intensive Care units at the University of Sao Paulo's Hospital Universitario (HU
      USP), and at checking the direct costs of the main activities in the process.
      This is an exploratory research, a retrospective, documental survey, using the
      case study model. The results showed that the total direct cost of the
      cardiopulmonary resuscitation training program was 9,081.44 reals. The direct
      cost with personnel represented 96.74%, and with material 3.26%. In the training
      planning sub-process, most of the direct cost was represented by the instructor
      assisting nurse, with 5,451.60 reals (62.04%). The direct costs related to the
      material that was used were also higher in the training program sub-process,
      188.80 reals (63.73%). The total cost per trainee was 206.40 reals.

PMID- 17542132
TI  - [Proposal for a model for calculating the size of nursing staff in home care].
AB  - Home care brings up issues related to the number of daily hours and days of
      nursing service from users of these services. This study was carried out in order
      to identify the criteria adopted by managers and nurses for calculating the
      nursing staff needed in home care services. Data were collected through semi
      structured interviews and analyzed according to the method of content analysis.
      Three categories were identified: patient's eligibility, time spent in care, and
      professional competency profile. The steps considered were: identification of
      daily average work load, choice of the proportion of professional categories,
      nursing workers' daily journey, and identification of the technical safety index
      for covering planned and unplanned absences. From these variables a model for
      calculating nursing personnel needed in home care is proposed in order to speed
      up the decision making process.

PMID- 17542133
TI  - [Use of the situational leadership in surgical center nursing].
AB  - This study was aimed at identifying the correspondence of opinions between nurses
      in surgical centers and the nursing team regarding the leadership style exercised
      by nurses and the leadership style these professionals should adopt in relation
      to the maturity level of their subordinates. Situational Leadership was adopted
      as a theoretical reference framework. We elaborated instruments that were
      submitted to appearance and content validation and then applied them to 15
      nurses, two technicians and 13 nursing auxiliaries. The results showed that the
      most frequent leadership style among nurses was E3 (to share). With respect to
      the leadership style nurses should adopt in relation to the maturity level of
      their subordinates in view of the activities in the operating room, style E4 (to
      delegate) predominated, which suggests that the studied subordinates present a
      high maturity level (M4).

PMID- 17542134
TI  - [Monitoring cancellations of surgical procedures: an indicator of organizational
      performance].
AB  - This descriptive and exploratory study aims at investigating the occurrence and
      causes for the cancellations of scheduled surgeries in the Surgical Center unit
      of a large school hospital in the interior of the State of Sao Paulo. Data were
      collected during three consecutive months in 2004 using institutional documents
      and forms elaborated by the researchers. In the period of study, 4,870 surgeries
      were scheduled in the investigated unit, of which 249 were suspended, an average
      of 5.1%. The main causes for the cancellations concerned the patients (57.8%),
      such as his/her absence (56.3%) and his/her unfavorable clinical conditions
      (34.7%); the unit's organization (22.1%), due to the lack of available beds for
      hospitalization (29.1%) and the occurrence of emergency surgeries (25.5%); and
      the allocation of human resources (17.7%) or of material resources and equipment
      (1.6%).

PMID- 17542135
TI  - [Occupational exposure of health care workers to organic fluids and adhesion to
      chemoprophylaxis].
AB  - This study was aimed at investigating the characteristics of occupational
      accidents and of the workers that suffered them, and at evaluating the adhesion
      to chemoprophylaxis and to control and follow up tests after occupational
      accidents with risk of contamination by the human immunodeficiency virus and of
      the hepatitis B and C virus. This is a descriptive epidemiological study whose
      data was collected from the notifications of one of the administrative regions of
      the State of Sao Paulo's Secretary of Health between 2000 and 2001. It was
      observed 7.3% of refusals for chemoprophylaxis against human immunodeficiency
      virus by antiretrovirals, and that 40.6% of the care workers who accepted the
      chemoprophylaxis did not complete the treatment in the four weeks estimated for
      it. This diagnosis highlights the need for the institutions involved to establish
      strategies that make possible an increase in the adherence of health workers to
      these care procedures.

PMID- 17542136
TI  - [Adaptation to the Portuguese language and validation of the Lunney Scoring
      Method for Rating Accuracy of Nursing Diagnoses].
AB  - The Lunney Scoring Method for Rating Accuracy of Nursing Diagnoses (LSM) is a
      semantic differential scale developed by Lunney to rate the accuracy of nursing
      diagnoses. The objective of this study was to adapt the LSM to the Portuguese
      language and to estimate its psychometric properties. The original scale was
      translated into Portuguese, back-translated into English, and the English
      versions were compared in order to adjust the Portuguese one (Escala de Acuracia
      de Diagnostico de Enfermagem de Lunney--EADE). Four nurses were trained on the
      EADE and applied it on 159 diagnoses made for 26 patients of three primary
      studies, based on the records of patients' interviews and physical examinations.
      Cohen's Kappa estimates produced unacceptable inter-observer agreement rates,
      showing that the adapted tool has not acceptable reliability. Because of this
      result, validity tests were not conducted.

PMID- 17542137
TI  - [Chronic pain and the belief in self-efficacy].
AB  - The treatment of chronic pain patients includes beliefs, attitudes, values and
      behavior modifications. Dysfunctional beliefs about pain and management can
      become the central problem and determine the treatment's outcome. Among the
      important beliefs for the management of chronic pain, self-efficacy deserves to
      be highlighted. The concept of self-efficacy, developed by Bandura, is the belief
      on the individual ability to perform successfully certain tasks or behaviors in
      order to produce a desired outcome. This study is a critical review of the
      literature on the belief of self-efficacy related to chronic pain and about the
      methods to assess self-efficacy. Studies listed in Medline (1992 to 2002), Lilacs
      and Dedalus (the entire databases) were analyzed. The key words were pain and
      self-efficacy, dor and auto-eficacia.

PMID- 17542138
TI  - [Patients' classification systems as management tools at intensive care units].
AB  - This study is a theoretical approach to different care and management measuring
      tools used to determine the severity of patients' illnesses, to quantify
      patients' care demands, and to estimate the actual need for Nursing professionals
      and the costs of intensive care, which makes them management facilitators. This
      article presents several measuring tools that are focused on the classification
      of patients at Intensive Care Units (ICUs) considering both the severity of
      illnesses and the Nursing staff's workload. Facilities and difficulties inherent
      to the application of these instruments are discussed.

PMID- 17542139
TI  - [Korotkoff sounds: development of the sphygmomanometry research at the Nursing
      School of the USP].
AB  - This article pays homage to Sergei Nicolai Korotkoff, for the centenary of the
      auscultatory method discovery. It refers to his discover of blood pressure
      auscultatory method in Russia, in 1905; presents the evidence that resulted in
      the development of sphygmomanometry studies in Brasil; describes the important
      contribution of the Nursing School of the University of Sao Paulo to the
      development of blood pressure measurement research; and analyses the results of
      the research field of "Cuff width influence in blood pressure measurement",
      created at the Nursing School of The University of Sao Paulo, in 1974. The
      scientific results of doctoral studies are presented, identifying the research
      groups that are contributing to defying knowledge in this area. The article
      demonstrates the consolidation of the results related to the initial doctoral
      program studies developed in the area. Confirmation of hypothesis in longitudinal
      studies is emphasized.

PMID- 17542140
TI  - [Demands for attention experienced by a patient in a bone marrow transplants
      unit].
AB  - The capacity to focus attention is essential for the effective handling of
      everyday life for it allows one to perceive, think clearly and keep the intended
      activity in course despite environmental distractions. This qualitative
      approached study was aimed at identifying the attention demands experienced by a
      patient diagnosed with sharp myeloid leukemia submitted to a bone marrow
      transplants (BMT) following the theoretical reference of attention and attention
      demands. The data was collected through a semi-structured interview and a
      systematic observation, with later content thematic analysis. The results pointed
      out that the patient in BMT lives multiple attention demands, such as: absence of
      family, fear of death, uncertainty about the future, restricted physical space,
      removal from work and too much handling by the Nursing staff, among others.

PMID- 17542141
TI  - [Thoughts on the preparation of nursing graduate students for undergraduate
      teaching].
AB  - It is noticeable the greater focus on scientific production in Graduate courses
      compared to the attention given to the preparation for teaching practices. This
      is a relevant issue considering the importance of having Masters and Doctors also
      prepared to form professionals in their area. This article discusses some aspects
      of the preparation of Graduate level students enrolled in the Teaching
      Improvement Program (Programa de Aperfeicoamento de Ensino, PAE), which the
      University of Sao Paulo offers. It also describes the experience of students who
      participate in the program, emphasizing its contribution to the development of
      competences for college teaching in Nursing.

PMID- 17542142
TI  - A view from the other side of the bed.

PMID- 17542144
TI  - Policy brief: North Dakota Health Care Workforce: planning together to meet
      future health care needs.

PMID- 17542145
TI  - Nursing that works: mastering the job interview.

PMID- 17542146
TI  - Communication: patient safety and the nursing work environment.

PMID- 17542147
TI  - Registered nurse utilization of nursing assistive personnel statement for
      adoption.
AB  - The Center for American Nurses (the Center) recognizes that in today's health
      care environment the NAP will be utilized to provide support to Registered Nurses
      in providing patient care. In delegating, it is the Registered Nurse who uses
      professional judgment to determine the appropriate activities to delegate. The
      determination is based on the concept of protection of the public (patient
      safety) and includes consideration of the needs of the patients, the education
      and training of the nursing assistive staff, the extent of supervision required,
      and the staff workload. Assessment, planning, evaluation and nursing judgment
      cannot be delegated. Any nursing implementation or intervention that requires
      independent, specialized, nursing knowledge, skill or judgment cannot be
      delegated. "The Registered Nurse is accountable for the delegation decision, the
      process and the ongoing monitoring of the outcomes of nursing care."

PMID- 17542148
TI  - Congestive heart failure.

PMID- 17542149
TI  - Patient-VU by ImplantVision": creating impressive, effective, and efficient
      dental implant consultations.

PMID- 17542150
TI  - Apricitabine: a novel deoxycytidine analogue nucleoside reverse transcriptase
      inhibitor for the treatment of nucleoside-resistant HIV infection.
AB  - Existing nucleoside reverse transcriptase inhibitors for HIV disease are limited
      by problems of resistance and, in some cases, long-term toxicity. Apricitabine
      (ATC; formerly BCH10618, SPD754 and AVX754) is a deoxycytidine analogue
      nucleoside reverse transcriptase inhibitor in clinical development. ATC retains
      substantial in vitro activity against HIV-1 containing many mutations associated
      with nucleoside reverse transcriptase inhibitor resistance, showing a less than
      twofold reduction in susceptibility in the presence of either up to five
      thymidine analogue mutations or the M184V mutation. ATC showed a low potential
      for cellular or mitochondrial toxicity in vitro. ATC is well absorbed orally,
      with a bioavailability of 65-80%. Its plasma elimination half-life (approximately
      3 h), and the intracellular half-life of its triphosphate (TP) metabolite (6-7 h)
      support twice-daily dosing. Intracellular ATC-TP levels are markedly reduced in
      the presence of lamivudine or emtricitabine, indicating that clinical co
      administration of ATC together with these agents will not be possible. The drug
      is renally eliminated, giving a low potential for hepatic drug interactions. In a
      double-blind, randomized, placebo-controlled Phase II monotherapy trial in
      antiretroviral-naive patients, ATC doses of 1,200 and 1,600 mg/day reduced plasma
      viral load levels by 1.65 and 1.58 log10 HIV RNA copies/ml, respectively, after
      10 days of treatment (P<0.0001 versus placebo). ATC showed a low propensity to
      select for resistance mutants in vitro and during clinical monotherapy. ATC was
      well tolerated in volunteers and in HIV-infected patients. This promising profile
      suggests that ATC may be useful in treating patients who have failed previous
      lamivudine- or emtricitabine-containing regimens. Further studies to evaluate the
      long-term efficacy and tolerability of ATC are underway.

PMID- 17542151
TI  - The threat of avian influenza H5N1: 'do we have the tools for the job'?
AB  - For the first time in human history virologists have the knowledge about the
      avian origin of pandemic influenza A viruses. Furthermore, in the last two
      decades a new class of anti influenza drugs, the neuraminidase inhibitors (NIs),
      has been developed from an academic discovery to a series of antiviral drugs to
      be used in the clinic. At present vaccinologists are producing influenza A (H5N1)
      vaccines to be stockpiled alongside the NIs to combat the first wave of an
      anticipated influenza pandemic. Studies from the 1918 infection calamity, the
      Spanish influenza, and the succeeding pandemics of 1957 and 1968, all caused by
      avian influenza A viruses, have shown how quickly such a virus can mutate to
      become less virulent (starting with 50% case fatality) and more infectious. Such
      a mutation cluster could lead to a rapid increase in world deaths, currently 170,
      to many millions. However there are optimistic analyses: judicious and swift
      application of NIs, vaccine and hygiene to an outbreak epicentre, most likely in
      South-East Asia, could break the chain of transmission.

PMID- 17542152
TI  - Effect of a plant polyphenol-rich extract on the lung protease activities of
      influenza-virus-infected mice.
AB  - Influenza infection was induced in white mice by intranasal inoculation of the
      virus A/Aichi/2/68 (H3N2). The lung protease and the protease-inhibitory
      activities were followed for 9 days after infection. The intranasal application
      of a polyphenol-rich extract (PC) isolated from Geranium sanguineum L. induced a
      continuous rise in the anti-protease activity but did not cause substantial
      changes in the lung protease activity of healthy mice. Influenza virus infection
      triggered a slight reduction in protease activity in the lungs at 5 and 48 h post
      infection (p.i.) and a marked increase at 24 h and 6 day p.i.. Protease
      inhibition in the lungs was reduced at 24 and 48 h p.i. and an increase was
      observed at 5 h and 6 and 9 days p.i.. PC treatment brought both activities to
      normal levels. The restoration of the examined parameters was consistent with a
      prolongation of mean survival time and reduction of mortality rate, infectious
      virus titre and lung consolidation. PC reinstated superoxide production by
      alveolar macrophages and increased their number in virus-infected mice. The
      favourable effect on the protease and the protease-inhibitory activities in the
      lungs of influenza-virus-infected mice apparently contributes to the overall
      protective effect of PC in the murine experimental influenza A/Aichi infection.
      The antiviral effect of the individual constituents was evaluated.

PMID- 17542153
TI  - Mechanism of action of (-)-(2R,4R)-1-(2-hydroxymethyl-1,3-dioxolan-4-yl) thymine
      as an anti-HIV agent.
AB  - (-)-(2R,4R)-1-(2-Hydroxymethyl-1,3-dioxolan-4yl)thymine (DOT) is a thymidine
      analogue that has potent in vitro activity against wild-type and nucleoside
      reverse transcriptase inhibitor (NRTI)-resistant HIV. For nucleoside analogues to
      inhibit viral replication, they must be metabolized to the active triphosphate,
      which inhibits the viral reverse transcriptase (RT). Using purified enzymes, the
      kinetics of DOT phosphorylation, inhibition of wild-type and drug-resistant HIV-1
      reverse transcriptase activity, and excision of DOT-5'-monophosphate (DOT-MP)
      from a chain-terminated primer were examined. DOT was phosphorylated by human
      thymidine kinase-1 (TK-1) but not by other pyrimidine nucleoside kinases,
      including the mitochondrial thymidine kinase (TK-2). Resistance to NRTIs involves
      decreased binding/incorporation and/or increased excision of the chain
      terminating NRTI. RTs containing the D67N/K70R/T215Y/K219Q or T695-SS/T215Y
      mutations show enhanced removal of DOT-MP from terminated primer as well as
      approximately four-fold decreased binding/incorporation. The Q151M and K65R
      mutations appear to cause decreased inhibition by DOT-TP. However, both the K65R
      and Q151M mutations show decreased excision, which would confer greater stability
      on the terminated primer. These opposing mechanisms could offset the overall
      resistance profile and susceptibility. Little or no resistance was observed with
      the enzymes harbouring mutations resistant to lamivudine (M184V) and non
      nucleoside RT inhibitors (K103N).

PMID- 17542154
TI  - Kinetics of inhibition of HIV type 1 reverse transcriptase-bearing NRTI
      associated mutations by apricitabine triphosphate.
AB  - We wished to investigate the effects of various mutations in HIV-1 reverse
      transcriptase (RT) on biochemical inhibition by the active form of a novel
      nucleoside termed apricitabine. Accordingly, we studied the efficiency of chain
      termination mediated by apricitabine triphosphate (TP) in cell-free assays that
      used either recombinant wild-type or mutated RTs. We also performed steady-state
      kinetics and primer-unblocking assays. Subtype C RTs were also analysed. The
      results showed that the K65R mutation in RT caused reductions in the efficiency
      of chain-termination of apricitabine-TP by increasing its Ki. However, K65R did
      not affect rates of primer unblocking for apricitabine-TP. No significant
      differences were found between subtype C and subtype B RTs with regard to any of
      the parameters studied. Other mutations such as M184V, L74V and K103N had no
      effect on the efficiency of chain termination by apricitabine-TP. Thus, the
      mechanism of reduced susceptibility to apricitabine of viruses containing K65R in
      RT seems to be mediated exclusively through a reduction in binding or
      incorporation of apricitabine-TP. Unlike some other nucleoside analogues,
      increased excision of incorporated apricitabine does not seem to be a cause of
      resistance to apricitabine.

PMID- 17542155
TI  - Tropolone and its derivatives as inhibitors of the helicase activity of hepatitis
      C virus nucleotide triphosphatase/helicase.
AB  - In this report, we demonstrate the interaction of the non-structural protein 3
      (NS3) of hepatitis C virus (HCV) with alkaloide tropolone (2-hydroxy-2,4,6
      heptatriene-1-one) and its derivatives. The compounds were biochemically screened
      separately against the ATPase and helicase activities of HCV NS3. In the
      investigations presented, alkaIoide tropolone and its derivatives significantly
      inhibited the helicase activity of the viral protein when using a DNA substrate,
      with 50% inhibitory concentration values within a low micromolar range. The
      results using the RNA substrate were unexpected--none of the tropolone
      derivatives excerted any modulating influence towards the unwinding activity.
      Surprisingly, no influence of the nucleoside triphosphatase (NTPase) turnover was
      observed. Evidence is presented confirming that these compounds do not act by
      blocking the NTP-binding site, but by occupying an additional allosteric
      regulatory site. Further mechanisms of action, particularly of some of the
      derivatives, are discussed.

PMID- 17542156
TI  - Joint attention and word learning in Ngas-speaking toddlers in Nigeria.
AB  - This study examines infants' joint attention behavior and language development in
      a rural village in Nigeria. Participants included eight younger (1 ;0 to 1 ;5, M
      age = 1 ;2) and eight older toddlers (1 ;7 to 2;7, M age= 2;1). Joint attention
      behaviors in social interaction contexts were recorded and coded at two time
      points six months apart. Analyses revealed that these toddlers were producing
      more high-level joint attention behaviors than less complex behaviors. In
      addition, the quality and quantity of behaviors produced by these Nigerian
      children was similar to those found in other cultures. In analyses of children's
      noun and verb comprehension and production (in relation to the number of nouns or
      verbs on a parental checklist), parents reported proportionally more verbs than
      nouns, perhaps because Ngas has some linguistic characteristics that are similar
      to languages in which a noun bias is not seen (e.g. Mandarin Chinese). An
      examination of the interrelations of joint attention and language development
      revealed that joint attention behaviors were related to both noun and verb
      development at different times. The set of results is important for understanding
      the emergence of joint attention in traditional cultures, the comprehension and
      production of nouns and verbs given the specific linguistic properties of a
      language, and the importance that early social contexts may have for language
      development.

PMID- 17542157
TI  - Spoken word recognition by Latino children learning Spanish as their first
      language.
AB  - Research on the development of efficiency in spoken language understanding has
      focused largely on middle-class children learning English. Here we extend this
      research to Spanish-learning children (n=49; M=2;0; range= 1 ;3-3; 1) living in
      the USA in Latino families from primarily low socioeconomic backgrounds. Children
      looked at pictures of familiar objects while listening to speech naming one of
      the objects. Analyses of eye movements revealed developmental increases in the
      efficiency of speech processing. Older children and children with larger
      vocabularies were more efficient at processing spoken language as it unfolds in
      real time, as previously documented with English learners. Children whose mothers
      had less education tended to be slower and less accurate than children of
      comparable age and vocabulary size whose mothers had more schooling, consistent
      with previous findings of slower rates of language learning in children from
      disadvantaged backgrounds. These results add to the cross-linguistic literature
      on the development of spoken word recognition and to the study of the impact of
      socioeconomic status (SES) factors on early language development.

PMID- 17542158
TI  - What part of no do children not understand? A usage-based account of multiword
      negation.
AB  - The study investigates the development of English multiword negation, in
      particular the negation of zero marked verbs (e.g. no sleep, not see, can't
      reach) from a usage-based perspective. The data was taken from a dense database
      consisting of the speech of an English-speaking child (Brian) aged 2;3-3;4 (MLU
      2.05-3.1) and his mother. The focus of the study was the emergence and usage of
      negators in the child's and mother's speech (e.g. no, not, can't, won't, don't).
      Two analyses were conducted: firstly, the emergence and usage of all negators in
      Brian's speech and in the input were calculated in order to present an overall
      picture of negator usage across the sample. The findings indicate a gradual and
      systematic development of negator selection in Brian's speech which follows the
      trajectory no-not-'nt. The pattern of negator emergence was found to follow the
      frequency of negators in the input; that is negators used frequently in the input
      were the first to emerge in the child's speech. Secondly, a more fine-grained
      analysis of utterances containing negated zero marked verbs (neg V utterances)
      was conducted on both the child's and mother's speech. In the first instance the
      development of negator selection for all neg V utterances was calculated. The
      results indicated the same no-not-'nt cline as attested in the initial analysis.
      A function-based analysis of neg V utterances was also conducted which indicated
      that the speed of movement across the no-not-'nt cline varied from one function
      to the next. A function-based analysis of the input suggested that the speed at
      which Brian moved across the cline within a particular function could be traced
      to function-based frequency effects in the input. Thus the findings of the study
      indicate function-based, input-driven learning which is consistent with the usage
      based approach. However the findings also indicate creative learning on the part
      of the child from the earliest stages of multiword negation.

PMID- 17542159
TI  - Size and composition of the lexicon in prematurely born very-low-birth-weight and
      full-term Finnish children at two years of age.
AB  - This paper focuses on the aspects of the lexicon in 66 prematurely born very-low
      birth-weight and 87 full-term Finnish children at 2;0, studied using the Finnish
      version of the MacArthur Communicative Developmental Inventory. The groups did
      not differ in vocabulary size. Furthermore, the female advantage in vocabulary
      size was not seen in preterm children. The overall shapes of the trajectories for
      the main lexical categories as a function of vocabulary size were highly similar
      in both groups and followed those described in the literature. However, there
      were significant differences in the percentage of nouns and grammatical function
      words between the two groups. The results suggest that prematurity 'cuts off' the
      female advantage in vocabulary development. Furthermore, it also seems that there
      are differences between prematurely born and full-term children in the
      composition of the lexicon at 2;0. The findings support the universal sequence in
      the development of lexical categories.

PMID- 17542160
TI  - Spatial language in Williams syndrome: evidence for a special interaction?
AB  - We present data on the language of space in Hungarian individuals with Williams
      syndrome (WS; 19 in the first, 15 in the second study, between 8; and 21; 11) and
      a verbal control (VC) group of typically developing (TD; 19 in the first, 15 in
      the second study, between 3;5 and 10;7) children from: (1) a study of elicited
      production and comprehension of spatial terms; and (2) a sentence completion task
      on case markers in their spatial and non-spatial use. The first study showed
      poorer performance in the WS group, but similar performance patterns and a
      special difficulty of SOURCE terms in both groups. We did not find overall group
      differences in the second study. We argue that WS performance patterns reflect WS
      spatial abilities and seem to be constrained by the same factors in WS as in TD.
      Results also lead us to conclude that, contrary to most previous claims, there is
      no selective deficit of spatial terms within WS language, and they also suggest
      that not all uses of spatial terms require activation of mental models of space.

PMID- 17542161
TI  - Child and adult construal of restrictive relative clauses: knowledge of grammar
      and differential effects of syntactic context.
AB  - We report four act-out experiments testing the sensitivity of adults and three-
      to five-year-old children to the distinction between restrictive and non
      restrictive relative clauses in English. Specifically, we test knowledge of the
      fact that restrictive relative clauses cannot modify a proper name head, and of
      the fact that relatives introduced by that (as opposed to a wh-pronoun) are
      obligatorily restrictive. Both children and adults show knowledge of these
      properties. No support was found for the hypothesis that children extend the
      block on proper name heads to wh-relatives. Both children and adults are
      sensitive to the syntactic context (double object vs. existential) in which the
      relative clause is embedded. However, adults differ from children in four
      respects. First, in the double object context, adults are more likely than
      children to commit the error of construing a that relative as referring to a
      proper name head. Second, the effect of syntactic context on selection of a head
      is larger for adults than for children. Third, for adults, but not for children,
      the effect of syntactic context interacts with the type of relative clause.
      Fourth, adults, but not children, are influenced by whether they hear the
      existential context before the double object context. We propose that by three to
      four years of age children have acquired an adult-like grammar of relative
      clauses, and that the differences we see in child and adult performance can be
      attributed to that grammar in combination with a mature (adult) or immature
      (child) sentence processing capacity.

PMID- 17542162
TI  - French children's use and correction of weird word orders: a constructivist
      account.
AB  - Using the weird word order methodology (Akhtar, 1999), we investigated children's
      understanding of SVO word order in French, a language with less consistent
      argument ordering patterns than English. One hundred and twelve French children
      (ages 2; 10 and 3; 9) heard either high or low frequency verbs modelled in either
      SOV or VSO order (both ungrammatical). Results showed that: (1) children were
      more likely to adopt a weird word order if they heard lower frequency verbs,
      suggesting gradual learning; (2) children in the high frequency conditions tended
      to correct the ungrammatical model they heard to the closest grammatical
      alternative, suggesting different models activated different grammatical schemas;
      and (3) children were less likely to express the object of a transitive verb than
      were English children in an equivalent study, suggesting object expression is
      more difficult to master in French, perhaps because of its inconsistency in the
      input. These findings are discussed in the context of a usage-based model of
      language acquisition.

PMID- 17542163
TI  - Acquisition of verb meaning through syntactic cues: a comparison of children with
      autism, children with specific language impairment (SLI) and children with
      typical language development (TLD).
AB  - The ability to extract meaning through the use of syntactic cues, adapted from
      Naigles' (1990) paradigm, was investigated in Hebrew-speaking children with
      autism, those with specific language impairment (SLI) and those with typical
      language development (TLD), in an attempt to shed light on similarities and
      differences between the two diagnostic categories, both defined by primary
      language deficits. Thirteen children with autism and 13 with SLI were matched on
      chronological age, level of language functioning and gender, and 13 children with
      TLD were matched to the children in the two clinical groups according to language
      level, as measured by the CELF-P. Children with autism and children with TLD
      learned novel words using the syntactical cues in the sentences in which they
      were presented, whereas children with SLI experienced more difficulty, learning
      only that which would be expected from chance according to the binomial test.
      Only 4 of the 13 children with SLI (31%) learned the new words, whereas 11
      children with autism and 10 children with TLD learned the novel verb using
      syntactical cues from the sentence frame. The results are analyzed in terms of
      possible underlying mechanisms in language acquisition. Children with autism seem
      to rely on relatively intact syntactic abilities, while children with SLI seem to
      have marked impairment in using this mechanism in acquiring word meaning.
      Implications for future research and intervention with preschool children with
      primary language disorders are discussed.

PMID- 17542164
TI  - When memorized instances compete with rules: the case of number-noun agreement in
      written French.
AB  - It is claimed by Totereau, Thevenin & Fayol (1997) that French children
      understand the rule for spelling the plural inflection very early on. However, no
      evidence contradicts the alternative that they learn the spelling of a word's
      singular and plural forms by treating the two forms as entirely different words.
      We tested this by asking French first and second graders (85 six-year-old and 89
      seven-year-old children, respectively) to read and write rare words, either in
      just the singular or in just the plural, and then testing their spelling. The
      children tended to attach plural inflections to words which they had encountered
      only as plural and to omit them from words encountered before only as singular.

PMID- 17542165
TI  - Advancing the science of nursing education: rethinking the meaning and
      significance of impact factors.
AB  - It is not the case that impact factors are unhelpful and that their use should be
      abolished. Indeed, ISI is continuing to refine existing and develop new databases
      to provide important information to researchers, administrators, librarians, and
      editors. Impact factor data do provide useful information for the review process
      if used judiciously and with an awareness of what these data do and do not
      indicate. Perhaps it is timely for members of the nursing discipline to think
      more broadly about the nature of impact and to talk more about the ways in which
      review processes can account for the many ways the impact of research can be
      demonstrated. For example, as part of the review process, reviewers might ask
      each researcher to provide exemplars from teaching or clinical practice settings
      in which their research is actually being used. Researchers might also be asked
      to describe the impact that has occurred in ways other than through publication
      (e.g., presentations, consulting) and how this impact was determined. Creating
      review processes that allow researchers to describe their decision making related
      to disseminating their research and how this reflects their ability to influence
      the discipline may provide a more realistic picture of impact than calculated
      figures alone.

PMID- 17542166
TI  - The accreditation process: a site visit encounter.
AB  - This column provides an overview of the process of a site visit by appraisers
      from the American Nurses Credentialing Center Commission on Accreditation.
      Various components of the accreditation process are discussed.

PMID- 17542167
TI  - Body contouring following major weight loss.
AB  - Body contouring is a highly specialized and quickly growing field of plastic
      surgery. This article describes some of the types of body contouring surgery
      individuals who have experienced massive weight loss may seek.

PMID- 17542168
TI  - The etiquette advantage: the nurse's toolbox.
AB  - Workplace etiquette is an important tool that all professionals can use to help
      with career advancement and success. This article describes some of the key
      components of workplace etiquette.

PMID- 17542169
TI  - Needs assessments: an array of possibilities.
AB  - The first step in planning any professional development activity is to assess the
      learning needs of the target group or individual to determine the structure of
      the program in terms of objectives, content, and activities. Learning needs can
      be individual, organizational, or societal and must be clearly defined during the
      planning process. This article provides an overview of the different types of
      needs assessments and discusses the importance of triangulation when interpreting
      data.

PMID- 17542170
TI  - Developing clinical leadership capability.
AB  - Nursing facilities must be committed to ongoing leadership development and to
      developing and retaining their staff in the increasingly competitive healthcare
      market. In this article, the authors share the processes involved in creating a
      focused small group approach to developing clinical leaders. Programmatic
      approaches to development, clarity of needs of those targeted for development,
      individual development plans, external expertise partnerships, and small group
      session dynamics are discussed. Applications of the process and lessons learned
      from the program will benefit others in their efforts to enhance organization
      succession planning, leadership development, group learning, and program
      administration.

PMID- 17542171
TI  - Outcomes of continuing education in the care of children with asthma for
      pediatric healthcare providers.
AB  - In this study, the authors assessed the knowledge of healthcare providers
      regarding asthma care, examined the outcomes of continuing education for asthma
      care, and explored the relationships among demographic characteristics of the
      healthcare providers and the improvement in asthma care knowledge. Thirty-one
      pediatricians and 38 nurses in the pediatric units of a medical center completed
      a questionnaire before and after an asthma care program. Pediatricians and
      pediatric nurses provided correct answers to asthma care questions 84.45% and
      61.97% of the time, respectively, before the program and 93.06% and 88.03% of the
      time, respectively, after the program, which was a significant improvement (p <
      .001). No significant correlations or differences were found between the changes
      in asthma care knowledge and the demographic characteristics of healthcare
      providers. Results from this study suggest that continuing education can improve
      the knowledge of asthma care among pediatric healthcare providers.

PMID- 17542172
TI  - Computer-assisted instruction for novice nurses in critical care.
AB  - The current worldwide nursing shortage is having the greatest effect on the
      critical care areas as novice nurses enter these specialty areas in unprecedented
      numbers. Massive healthcare restructuring, a rapidly aging nursing work force,
      and high nursing turnover and absenteeism rates have all contributed to a
      healthcare environment that is struggling to care for critically ill patients.
      Computer-assisted instruction in the form of interactive computer programs may be
      used as an adjunct educational resource for these novice practitioners. These
      programs have the potential to bridge the gap between theory and practice, which
      may assist the novice nurse in achieving safe, competent clinical practice.

PMID- 17542173
TI  - Distance education and the integration of E-learning in a graduate program.
AB  - Historically, distance education consisted of a combination of face-to-face
      blocks of time and surface mailed packages. However, advances in information
      technology literacy and the abundance of personal computers has placed e-learning
      in increased demand. The authors describe the planning, implementation, and
      evaluation of the blending of e-learning with face-to-face education in the
      postgraduate nursing forum. Experiences of this particular student group are also
      discussed.

PMID- 17542174
TI  - The biomechanics of situational baseball: execution and perception of left-handed
      pitchers' simulated pick-off moves to first base.
AB  - The aim of this study was to provide an in-depth analysis of the pick-off play in
      baseball. Ten collegiate left-handed pitchers and nine base-runners participated
      in this study. The pitchers were videotaped with four cameras to derive three
      dimensional data while performing deliveries in the directions of first base and
      home plate in a laboratory setting. Deliveries were performed from flat ground.
      Differences between these deliveries were measured through ten selected joint and
      segment angles. The base-runners completed two distinct procedures in which they
      viewed video footage of left-handed pitchers and estimated the intended delivery
      direction. Base-runners were subsequently interviewed to determine the reasoning
      behind their decisions. The pitchers' data revealed differences between delivery
      types in nearly all of the selected angles (P < 0.01). The base-runners' data
      demonstrated that their ability to discriminate delivery types improved when
      allowed more viewing time per trial (P < 0.01). Additionally, commonalities exist
      among the base-runners' focal points on the pitcher while making decisions
      regarding delivery direction and the kinematic differences between deliveries in
      left-handed pitchers. The practical significance of these results, however, may
      be more difficult to interpret.

PMID- 17542175
TI  - Bat speed, trajectory, and timing for collegiate baseball batters hitting a
      stationary ball.
AB  - The aims of this study were to examine whether batters hit stationary balls at
      the time of peak speed of the bat head and whether the impact occurs at the
      lowest point of the bat trajectory. Eight university baseball players hit three
      balls, each hung with a string; each ball was made of a different material and
      was different in weight. Bat movement was captured by four 240-Hz infrared
      cameras and analysed three-dimensionally. Time for peak speed of the bat head
      varied according to the conditions. When stationary balls of standard weight were
      used, the bat head was at maximum speed at impact with the ball; then, it
      decelerated drastically owing to the impact. In contrast, maximum speed was
      obtained after impact when lightweight stationary balls were used. The time-speed
      profile of the bat head before impact in the lightweight ball condition was
      identical with that in the standard weight ball condition. Regardless of
      conditions, the timing of the lowest point of the bat head was nearly identical
      for each batter and most participants hit the stationary balls at about the
      lowest point of the bat trajectory.

PMID- 17542176
TI  - Effective force and economy of triathletes and cyclists.
AB  - The effective force applied on the crank, the index of pedalling effectiveness,
      and the economy of movement at 60, 75, 90, and 105 rev/min cadences were examined
      in nine cyclists and eight triathletes. Tests were performed on two days. Maximal
      oxygen uptake was measured and the second ventilatory threshold was estimated on
      day 1 using a stationary bicycle. On day 2, the four different cadences were
      tested at about 5% below the second ventilatory threshold. A strain gauge
      instrumented clip-less pedal mounted on the bicycle enabled us to measure the
      normal and tangential forces exerted on the pedal, while the pedal and crank
      angles were monitored with the aid of a video system. Based on this information,
      the effective force and the index of pedalling effectiveness were calculated.
      Cyclists produced significantly more effective force and a higher index of
      pedalling effectiveness at 60 and 75 rev/min and were significantly more economic
      at all cadences than triathletes. The significant and positive correlation
      between effective force and economy at all cadences suggests that improvement of
      the effective force would reflect on economy.

PMID- 17542177
TI  - Muscle cross-sectional areas and performance power of limbs and trunk in the
      rowing motion.
AB  - Although it is clear that rowers have a large muscle mass, their distribution of
      muscle mass and which of the main motions in rowing mediates muscle hypertrophy
      in each body part are unclear. We examine the relationships between partial
      motion power in rowing and muscle cross-sectional area of the thigh, lower back,
      and upper arms. Sixty young rowers (39 males and 21 females) participated in the
      study. Joint positions and forces were measured by video cameras and rowing
      ergometer software, respectively. One-dimensional motion analysis was performed
      to calculate the power of leg drive, trunk swing, and arm pull motions. Muscle
      cross-sectional areas were measured using magnetic resonance imaging. Multiple
      regression analyses were carried out to determine the association of different
      muscle cross-sectional areas with partial motion power. The anterior thigh best
      explained the power demonstrated by leg drive (r2 = 0.508), the posterior thigh
      and lower back combined best explained the power demonstrated by the trunk swing
      (r2 = 0.493), and the elbow extensors best explained the power demonstrated by
      the arm pull (r2 = 0.195). Other correlations, such as arm muscles with leg drive
      power (r2 = 0.424) and anterior thigh with trunk swing power (r2 = 0.33 5), were
      also significant. All muscle cross-sectional areas were associated with rowing
      performance either through the production of power or by transmitting work. The
      results imply that rowing motion requires a well-balanced distribution of muscle
      mass throughout the body.

PMID- 17542178
TI  - Identifying the optimal resistive load for complex training in male rugby
      players.
AB  - Alternating a resistance exercise with a plyometric exercise is referred to as
      "complex training". In this study, we examined the effect of various resistive
      loads on the biomechanics of performance of a fast stretch-shortening cycle
      activity to determine if an optimal resistive load exists for complex training.
      Twelve elite rugby players performed three drop jumps before and after three back
      squat resistive loads of 65%, 80%, and 93% of a single repetition maximum (1-RM)
      load. All drop jumps were performed on a specially constructed sledge and force
      platform apparatus. Flight time, ground contact time, peak ground reaction force,
      reactive strength index, and leg stiffness were the dependent variables. Repeated
      measures analysis of variance found that all resistive loads reduced (P < 0.01)
      flight time, and that lifting at the 93% load resulted in an improvement (P <
      0.05) in ground contact time and leg stiffness. From a training perspective, the
      results indicate that the heavy lifting will encourage the fast stretch
      shortening cycle activity to be performed with a stiffer leg spring action, which
      in turn may benefit performance. However, it is unknown if these acute changes
      will produce any long-term adaptations to muscle function.

PMID- 17542179
TI  - External work and peak power are reliable measures of ergometer grinding
      performance when tested under load, deck heel, and grinding direction conditions.
AB  - The reliability of grinding performance was assessed in 18 current Emirates Team
      New Zealand America's Cup sailors in two test sessions separated by 5 h using a
      custom-built ergometer. Sixteen different grinding conditions that varied by load
      (Light 39 N x m, Moderate 48 N x m, Heavy 68 N x m), deck heel (Flat 0 degrees
      control, Downhill 25 degrees, Uphill 25 degrees, Right 25 degrees, Left 25
      degrees), and grinding direction (forwards, backwards) were assessed using peak
      power and external work over 5 s during maximal-effort 8-s grinds. Reliability
      statistics included the difference in mean (M(diff)), standard error of
      measurement (SEM), and intraclass correlation coefficients (ICC). External work
      (SEM = 1.6-6.9%; ICC = 0.91-0.99) was a more consistent performance measure than
      peak power (SEM = 1.3-9.6%; ICC = 0.84-0.99) across all test conditions. Testing
      under different load conditions resulted in external work SEMs of 1.6-3.9% with
      performance more reliable in lighter load conditions. Grinding performance during
      different heel conditions was less reliable (external work SEMs = 4.6-6.9%).
      Grinding direction (forward or backward) did not appear to affect performance
      reliability, although external work was 10-15% higher in forward grinding.
      Reliability is acceptable across various loads, but testing under different heel
      conditions may need some protocol development to allow the detection of smaller
      differences in performance.

PMID- 17542180
TI  - The accuracy of computational fluid dynamics analysis of the passive drag of a
      male swimmer.
AB  - The aim of this study was to build an accurate computer-based model to study the
      water flow and drag force characteristics around and acting upon the human body
      while in a submerged streamlined position. Comparisons of total drag force were
      performed between an actual swimmer, a virtual computational fluid dynamics (CFD)
      model of the swimmer, and an actual mannequin based on the virtual model. Drag
      forces were determined for velocities between 1.5 m/s and 2.25 m/s
      (representative of the velocities demonstrated in elite competition). The drag
      forces calculated from the virtual model using CFD were found to be within 4% of
      the experimentally determined values for the mannequin. The mannequin drag was
      found to be 18% less than the drag of the swimmer at each velocity examined. This
      study has determined the accuracy of using CFD for the analysis of the
      hydrodynamics of swimming and has allowed for the improved understanding of the
      relative contributions of various forms of drag to the total drag force
      experienced by submerged swimmers.

PMID- 17542181
TI  - Laboratory versus field testing in cricket bowling: a review of current and past
      practice in modelling techniques.
AB  - In cricket bowling, the reconstruction of elbow angle data is of utmost
      importance to the bowling versus throwing argument. This paper reviews system and
      modelling errors inherent in three-dimensional reconstruction processes with
      respect to the elbow extension tolerance set by the International Cricket
      Council. An understanding of these factors will enable more informed decisions
      about the choice of in-field versus laboratory testing in the calculation of
      elbow extension during bowling in cricket. Although there is a paucity of
      objective data related to in-field and laboratory testing, biomechanists must be
      guided by the greater accuracy of opto-reflective than video-based systems and so
      testing, at least for the present, should be conducted in a laboratory setting.

PMID- 17542182
TI  - Qualitative biomechanical principles for application in coaching.
AB  - Many aspects of human movements in sport can be readily understood by Newtonian
      rigid-body mechanics. Many of these laws and biomechanical principles, however,
      are counterintuitive to a lot of people. There are also several problems in the
      application of biomechanics to sports, so the application of biomechanics in the
      qualitative analysis of sport skills by many coaches has been limited.
      Biomechanics scholars have long been interested in developing principles that
      facilitate the qualitative application of biomechanics to improve movement
      performance and reduce the risk of injury. This paper summarizes the major North
      American efforts to establish a set of general biomechanical principles of
      movement, and illustrates how principles can be used to improve the application
      of biomechanics in the qualitative analysis of sport technique. A coach helping a
      player with a tennis serve is presented as an example. The standardization of
      terminology for biomechanical principles is proposed as an important first step
      in improving the application ofbiomechanics in sport. There is also a need for
      international cooperation and research on the effectiveness of applying
      biomechanical principles in the coaching of sport techniques.

PMID- 17542183
TI  - The failure of war.

PMID- 17542184
TI  - The nuclear weapons inheritance project: student-to-student dialogues and
      interactive peer education in disarmament activism.
AB  - The Nuclear Weapons Inheritance Project is a student run and student initiated
      project founded in 2001 with the purpose of increasing awareness of health
      effects of nuclear policies and empowering university students to take action in
      a local and international context. The project uses dialogues to discuss nuclear
      disarmament with university students and a method of interactive peer education
      to train new trainers. The project has met more than 1500 students in nuclear
      weapon states in dialogue and trained about 400 students from all over the world.
      This article describes the methods and results of the project and discuss how the
      experience of the project can be used in other projects seeking to increase
      awareness of a topic and to initiate action on social injustice.

PMID- 17542185
TI  - Conflict induced internal displacement in Nepal.
AB  - Nepal has witnessed a humanitarian crisis since the Maoist conflict began ten
      years ago. The plight of internally displaced persons (IDPs) in Nepal has
      received little international attention despite being rated one of the worst
      displacement scenarios in the world. An estimated 200,000 people have been
      displaced as a result of the conflict, with the far-western districts of Nepal
      being the worst affected. Internal displacement has stretched the carrying
      capacity of several cities with adverse physical and mental health consequences
      for the displaced. Vulnerable women and children have been the worst affected.
      The government has adopted a discriminatory approach and failed to fulfil its
      obligations towards IDPs. Non-governmental organisations and international
      agencies have provided inadequate services to IDPs in their programmes. Tackling
      the issues of IDPs requires co-operation between government and development
      agencies: acknowledging the burden of the problem of IDPs, adequate registration
      and needs assessment, along with health and nutritional surveys, and development
      of short-term emergency relief packages and long-term programmes for their
      assistance.

PMID- 17542186
TI  - The psychiatric defence and international criminal law.
AB  - Following the development of the International Criminal Court (ICC) the mental
      state of the perpetrators of genocide, crimes against humanity and war crimes
      will become a more important issue in regard to defence and mitigating factors.
      This article examines how the International Criminal Tribunal for the Former
      Yugoslavia (ICTY) in particular has dealt with the mental illness defence to
      date, and how its judgements can serve as guidance for the ICC as it becomes the
      major international court of the future. The absence of a mental health defence
      in the Statutes of the ICTY and the International Criminal Tribunal for Rwanda
      has led to a reliance on the Rules of Procedure and Evidence of the two
      tribunals. There are major difficulties in using the mental health defence as it
      is defined in the Statutes of the ICC because of a requirement for the
      destruction of mental capacity as a valid defence. Fitness to plead and the
      defence of intoxication are also examined.

PMID- 17542187
TI  - IPPNW renews call to reject war, embrace health: IPPNW 17th world congress.

PMID- 17542188
TI  - If you want peace, work for health!

PMID- 17542189
TI  - Medical students at an IPPNW World Congress: a growing force.

PMID- 17542190
TI  - Increase in violent deaths of Iraqi journalists since the 2003 invasion.

PMID- 17542191
TI  - Diagnosis of hyperadrenocorticism in dogs.
AB  - A presumptive diagnosis of hyperadrenocorticism in dogs can be made from clinical
      signs, physical examination, routine laboratory tests, and diagnostic imaging
      findings, but the diagnosis must be confirmed by use of pituitary-adrenal
      function tests. Screening tests designed to diagnose hyperadrenocorticism include
      the corticotropin (adrenocorticotropic hormone; ACTH) stimulation test, low-dose
      dexamethasone suppression test, and the urinary cortisol:creatinine ratio. None
      of these screening tests are perfect, and all are capable of giving false
      negative and false-positive test results. Because of the limitation of these
      diagnostic tests, screening for hyperadrenocorticism must be reserved for dogs in
      which the disease is strongly suspected on the basis of historical and clinical
      findings. Once a diagnosis has been confirmed, the next step in the workup is to
      use one or more tests and procedures to distinguish pituitary-dependent from
      adrenal-dependent hyperadrenocorticism. Endocrine tests in this category include
      the high-dose dexamethasone suppression test and endogenous plasma ACTH
      measurements. Imaging techniques such as abdominal radiography, ultrasonography,
      computed tomography, and magnetic resonance imaging can also be extremely helpful
      in determining the cause.

PMID- 17542192
TI  - Hyperadrenocorticism associated with sex steroid excess.
AB  - Diagnosis of sex steroid excess or hyperadrenocorticism in dogs may be
      challenging. Unlike Cushing's disease, sex steroid excess may have a multitude of
      manifestations that differ from standard hyperadrenocorticism. In particular, the
      clinical scenario of a dog with sex steroid imbalance involves one of three
      systems: dermatologic, reproductive, or hepatic. The history of a dog with
      hyperadrenocorticism manifesting as sex steroid imbalance often lacks the
      classical clinical signs of polydipsia and polyuria. Dogs with sex steroid
      imbalance will often be of specific breeds such as miniature poodles and exhibit
      trunkal hair loss as the only sign. There is often involvement of the
      reproductive system, manifested as the growth of perianal adenomas in neutered
      male or female dogs. The most common laboratory findings consist of elevations in
      serum alkaline phosphatase and serum alanine transferase. The following article
      reviews the etiology, common signalment, clinical signs, and laboratory findings
      associated with atypical hyperadrenocorticism caused by sex steroid imbalance and
      then explores the medical, surgical, and radiation treatment options.

PMID- 17542193
TI  - Medical management of pituitary-dependent hyperadrenocorticism: mitotane versus
      trilostane.
AB  - Pituitary-dependent hyperadrenocorticism is a common endocrine disorder in dogs
      in the United States. Once a diagnosis is established, a decision must be made
      whether or not to pursue treatment, and if so, which medication to use.
      Historically, mitotane (Lysodren, o,p'-DDD, Bristol-Myers Squibb, New York) has
      been the most commonly used treatment for medical management. Its use is
      complicated and comes with many potential side effects, making many practitioners
      wary of its use. Recently, trilostane has been proven to be an effective
      treatment of pituitary-dependent hyperadrenocorticism and is approved for use in
      other countries. Treatment with trilostane is somewhat simpler and the incidence
      of side effects seems to be less when compared with mitotane therapy. Either
      treatment can be a safe and effective method of treatment for pituitary-dependent
      hyperadrenocorticism when the practitioner and client are well educated regarding
      their use and an appropriate monitoring protocol is used.

PMID- 17542194
TI  - Feline adrenal disorders.
AB  - Although only recently discovered, feline adrenal disorders are becoming
      increasingly more recognized. Feline adrenal disorders include diseases such as
      hyperadrenocorticism (Cushing's syndrome) and hyperaldosteronism (Conn's
      syndrome). The clinical signs of feline hyperadrenocorticism, which include
      unregulated diabetes mellitus and severe skin atrophy, are unique to the cat.
      Other signs of feline hyperadrenocorticism, such as potbellied appearance,
      polydipsia, polyuria, and susceptibility to infections are also seen in dogs with
      hyperadrenocorticism. Conn's syndrome has only recently been described in the cat
      and is in fact more common in cats than in dogs. Characterized by severe
      hypokalemia, hypertension, and muscle weakness, Conn's syndrome may be
      misdiagnosed as renal failure. The clinician should become familiar with the
      clinical signs of adrenal disorders in cats and the common diagnostic tests used
      to diagnose these syndromes in cats as they differ from those in the dog.
      Treatment of feline adrenal disorders may be challenging; the clinician should
      become familiar with common drugs used to treat adrenal disorders in cats.

PMID- 17542195
TI  - Hypoadrenocorticism in small animals.
AB  - The diagnosis and treatment of hypoadrenocorticism can be one of the greatest
      challenges faced by veterinary practitioners, as Addison's disease may have many
      faces and many presentations. Although the disease is most often diagnosed in
      dogs, cats may also suffer from Addison's disease. The practitioner must have a
      high index of suspicion to make a diagnosis of hypoadrenocorticism. This index of
      suspicion is based on knowledge of the common signalment, history, physical
      examination, and laboratory findings. Diagnosis of hypoadrenocorticism is
      supported by appropriate choice of diagnostic endocrine tests that are described
      in detail in this article. Once a diagnosis of hypoadrenocorticism has been made,
      expedient treatment is of foremost concern. Timely treatment using fluids,
      corticosteroids, and supportive care will ensure a successful outcome; the
      emergency treatment of Addison's is covered briefly in this article and fully in
      another article in this issue. The purpose of this review was to describe the
      clinical diagnosis and chronic treatment of hypoadrenocorticism in dogs and cats.

PMID- 17542196
TI  - Treatment of acute adrenal insufficiency.
AB  - Hypoadrenocorticism is caused by a lack of endogenous glucocorticoid and
      mineralocorticoid. These deficiencies can cause a myriad of clinical signs. This
      disease is uncommon and its clinical presentation is similar to many much more
      commonly recognized diseases such as renal failure and various gastrointestinal
      disorders. Severely affected patients may present in a life-threatening
      adrenocortical crisis, which is characterized by variable degrees of volume
      depletion and electrolyte abnormalities. The emergency clinician should maintain
      a high clinical suspicion for hypoadrenocorticism, as early recognition and rapid
      treatment of hypovolemia and electrolyte abnormalities can be lifesaving. The
      approach to emergency treatment of hypoadrenocorticism should be to recognize and
      treat life-threatening arrhythmias, replace intravascular volume and normalize
      perfusion, correct electrolyte abnormalities and hypoglycemia, administer
      glucocorticoids, and perform the adrenocorticotrophic hormone stimulation test
      for definitive diagnosis. Patients with this condition should have a favorable
      outcome when treated appropriately.

PMID- 17542197
TI  - Considerations about enamel microabrasion after 18 years.
AB  - PURPOSE: To review of the current status of enamel microabrasion method and its
      results 18 years after the development and application of this method. METHODS: A
      technique performing enamel microabrasion with hydrochloric acid mixed with
      pumice and other techniques employing a commercially available compound of
      hydrochloric acid and fine-grit silicon carbide particles in a water-soluble
      paste have been described. Much has been learned about the application of this
      esthetic technique, long-term treatment results and microscopic changes to the
      enamel surface that has significant clinical implications. The latest treatment
      protocol is presented and photographic case histories document the treatment
      results. Clinical observations made over 18 years are discussed. RESULTS:
      According to our findings, the dental enamel microabrasion technique is a highly
      satisfactory, safe and effective procedure.

PMID- 17542198
TI  - Use of ultrasonography for the diagnosis of temporomandibular joint disorders: a
      review.
AB  - PURPOSE: To evaluate the reliability of ultrasonography in the diagnosis of
      temporomandibular joint (TMJ) disorders. METHODS: A review of the literature was
      performed, searching for all articles published between 1966 and 2006, and
      examining the ones which met the selection criteria. RESULTS: Ultrasonography
      sensitivity ranged from 13-100% for the evaluation of disc displacement (DD),
      from 70.6-83.9% for the evaluation of joint effusion (JE), and from 70-94% for
      the evaluation of condylar erosion (CE). Specificity ranged from 62-100% for the
      evaluation of DD, from 73.7-100% for the evaluation of JE, and from 20-100% for
      the evaluation of CE. Accuracy ranged from 51.5-100% for the evaluation of DD,
      from 72.2-95% for the evaluation of JE, and from 67-94% for the evaluation of CE.

PMID- 17542199
TI  - Clinical effectiveness of a dentifrice containing triclosan and a copolymer for
      controlling breath odor.
AB  - PURPOSE: To investigate in a double-blind clinical study the effectiveness of a
      dentifrice containing triclosan and a copolymer (Colgate Total Toothpaste) for
      controlling breath odor 12 hours after brushing the teeth. METHODS: A panel of
      four expert judges using a nine-point hedonic scale evaluated breath odor.
      Following a baseline evaluation of breath odor, prospective study subjects who
      presented breath odor scores above the threshold value for unpleasant breath odor
      were stratified by score, and randomized into two treatment groups. Subjects were
      provided with a soft-bristled toothbrush, and brushed their teeth thoroughly in
      their regular and customary manner with their assigned dentifrice. Subjects
      refrained from dental hygiene, breath mints, or mouthrinses for the next 12
      hours, after which they were once again evaluated for breath odor. 76 adult male
      and female subjects from the Mississauga, Ontario, Canada area participated in
      the study. RESULTS: At 12 hours after brushing their teeth, subjects in both
      dentifrice treatment groups presented mean breath odor scores which were
      statistically significantly lower than the mean scores observed at baseline.
      However, the difference between the mean 12-hour breath odor score for the
      Colgate Total group was 4.65, which is within the range of values corresponding
      to pleasant breath odor; whereas the mean 12-hour breath odor score for the
      placebo group was 6.11, which is above the threshold value corresponding to
      unpleasant breath odor. Thus, the results of this double-blind study, conducted
      according to Guidelines by the Council on Scientific Affairs of the American
      Dental Association, support the conclusion that Colgate Total dentifrice provides
      effective control of breath odor at 12 hours after brushing the teeth.

PMID- 17542200
TI  - Degradation of thermo-mechanically loaded adhesive Class V restorations after 18
      months of water storage.
AB  - PURPOSE: To assess in vitro the hydrolytic stability of adhesive systems in Class
      V composite restorations bonded to enamel and dentin. METHODS: 16 groups of Class
      V cavities restored with different adhesive systems and challenged with thermal
      and mechanical loading under the simulation of dentin fluid were evaluated after
      an 18-month period of water storage at 37 degrees C. The marginal adaptation of
      these restorations was quantified by evaluation of gold-coated epoxy replicas
      with scanning electron microscopy at x200 magnification. RESULTS: The percentages
      of "continuous margin" after 18 months of water storage with respect to the total
      marginal length ranged from 62.9 (5.4)% to 18.5 (3.2)% with significant
      differences observed among the groups (Bonferroni test P < 0.05). The range in
      enamel was from 71.8 (14.2)% to 8.9 (6.4)% and in dentin from 94.3 (5.1)% to 0.0
      (0.0)%. Marginal adaptation of all the materials tested was affected by water
      storage, either in enamel, in dentin, or both. None of the restorative systems
      tested exhibited hydrolytically stable marginal adaptation.

PMID- 17542201
TI  - Effect of manual and powered toothbrushes on orthodontic bracket bond strength.
AB  - PURPOSE: To assess in vitro the effect of manual and powered toothbrushes on the
      bond strength of orthodontic brackets. METHODS: Specimens of orthodontic brackets
      bonded to the surfaces of extracted teeth were exposed to one of two powered
      toothbrushes (Sonicare Elite, Braun Oral-B 3D Excel) or a manual toothbrush (Oral
      B 35) for the equivalent of a 2-year exposure to brushing in the presence of
      toothpaste slurry. Control specimens underwent no brushing. For each treatment,
      10 specimens were tested and evaluated. Shear bond strength of the orthodontic
      bracket to the tooth surface was assessed after exposure to simulated brushing.
      ANOVA was used to analyze the data. RESULTS: No differences in orthodontic
      bracket bond strength were observed between any of the three treatments and the
      control. The evaluated toothbrushes did not adversely affect the in vitro bonding
      strength of orthodontic brackets, suggesting they are safe to use in orthodontic
      patients.

PMID- 17542202
TI  - Remineralization of primary root caries lesions using an amine fluoride rinse and
      dentifrice twice a day.
AB  - PURPOSE: To assess the clinical effect of daily use of a toothpaste and
      mouthrinse, both containing amine fluoride, on primary root caries lesions (PRCL)
      in an adult caries risk population. METHODS: A clinical trial based on male and
      female subjects, 55-81 years of age, randomly assigned into two equal groups
      (Groups A and B). Fifty subjects allocated to Group A used a fluoride toothpaste
      twice a day, (Elmex sensitive toothpaste, 1400 ppm F) plus a mouthrinse twice a
      day with 10 ml of a fluoride solution (Elmex sensitive rinse containing 250 ppm
      F). The fluoride used was amine fluoride and potassium fluoride (AmF/KF, 1:1).
      Subjects in Group B used the same fluoride toothpaste plus a placebo mouth rinse
      solution without fluoride. At baseline, a total of 420 PRCL were clinically
      recorded as either soft (score 3) or leathery (score 2). Parallel and blind
      recordings measuring electric resistance of the selected PRCL were performed at
      baseline and after 3, 6, 9 and 12 months using an electrical caries monitor
      (ECM). Prevalence of tooth sensitivity and subject's satisfaction was also
      measured in the two groups. RESULTS: The clinical results showed statistically
      significant higher numbers of reversals of soft (score 3) and leathery (score 2)
      PRCL in Group A compared to Group B. After 12 months, the number of soft PRCL
      (score 3) decreased in Group A from 74% at baseline to 11% compared with 73% to
      46% in Group B. After 12 months, 67% of the PRCL became hard (score 1) in Group A
      compared to only 7% in Group B (P < 0.001). Statistically significant higher (P <
      0.001) ECM mean (sd) log10 resistance values were recorded for the subjects in
      Group A, 2.67 (2.56) kOhm compared to 2.12 (1.88) kOhm in Group B. Tooth
      sensitivity was substantially reduced after 12 months, by 56% in Group A compared
      to 20% in Group B.

PMID- 17542203
TI  - Micromorphology and surface roughness of sound and demineralized enamel and
      dentin bleached with a 10% carbamide peroxide bleaching agent.
AB  - PURPOSE: To evaluate the micromorphology and surface roughness of sound and
      demineralized enamel and dentin treated with a 10% carbamide peroxide bleaching
      agent in situ for 3 weeks. METHODS: A 10% carbamide peroxide bleaching agent,
      Opalescence (OPA) was evaluated and a placebo agent (PLA) not containing
      carbamide peroxide, was used as a control group. Forty dental slabs [10 sound
      enamel slabs (SE), 10 demineralized enamel slabs (DE), 10 sound dentin slabs (SD)
      and 10 demineralized dentin slabs (DD)] were randomly fixed on the facial surface
      of the first maxillary molars and second maxillary premolars of 10 volunteers.
      Demineralized enamel and dentin fragments were obtained by a dynamic model using
      demineralizing and remineralizing solutions. The volunteers were divided into two
      groups that received the bleaching or the placebo agent in different sequences
      and periods in a double blind 2 x 2 cross-over study with a wash-out period of 2
      weeks. Roughness was performed on the slab surfaces followed by scanning electron
      microscope (SEM) evaluations. The images were evaluated by three calibrated
      examiners in duplicate in two different periods at x1500 (SE and DE) and x2000
      original magnification (SD and DD). RESULTS: The Wilcoxon test showed significant
      differences in roughness for SE and DE treated with OPA or PLA, with rougher
      surfaces treated with OPA. No differences in roughness were observed for SD or DD
      treated with OPA or PLA. As the Kappa value for the inter-examiner agreement of
      SEM evaluations showed "moderate" reproducibility (0.41 < k< 0.60) in Period 1
      and "substantial" (0.61 < k < 0.8) in Period 2, the latter was considered for the
      statistical analysis. The McNemar test showed no significant differences between
      SE, DE, SD or DD treated with OPA or PLA.

PMID- 17542204
TI  - Influence of ceramic pre-treatments on tensile bond strength and mode of failure
      of resin bonded to ceramics.
AB  - PURPOSE: To evaluate the effect of ceramic surface treatments on tensile bond
      strength (sigma) and the mode of failure of a resin bonded to a feldspathic glass
      and a low-crystalline ceramic, testing the hypothesis that a silica coating
      treatment is unnecessary for both the glass and the low-crystalline ceramic.
      METHODS: 10 blocks of each the feldspathic glass (V7-VITAVM7) and the leucite
      based ceramic (E1-IPS Empress) were fabricated and polished. Five blocks of each
      ceramic were treated as follows: 9.5% hydrofluoric acid for 60 seconds; and
      silica coating using Cojet System for 15 seconds. After silane coating, an
      adhesive resin and a composite were applied and polymerized. The composite
      ceramic blocks were cut to produce bar-shaped specimens (n = 30) that were stored
      in distilled water at 37 degrees C for 7 days before tensile loading to failure
      in a universal testing machine. Data were statistically analyzed using analysis
      of variance, Tukey's test (alpha = .01) and Weibull analysis. Fracture surfaces
      were examined to determine the mode of failure. RESULTS: The Weibull modulus (m)
      and mean sigma value (MPa) of Group E1HF (29.8 +/- 4.5) were significantly higher
      than other Groups (P = .0001). There was no statistical difference between Groups
      E1CS (24.6 +/- 5.6) and V7HF (22.3 +/- 4.0). Group V7CS showed the lowest m and
      mean sigma values (15.7 +/- 6.9) (P = .0001). All fractures occurred within the
      adhesion zone.

PMID- 17542205
TI  - Degradation of resin-bonded human dentin after 3 years of storage.
AB  - PURPOSE: To test, in vitro, the null hypothesis that there was no difference in
      the ultrastructure of adhesive-bonded, acid-etched dentin aged under accelerated
      conditions in mineral oil or artificial saliva. METHODS: Beams of human dentin
      bonded with three total-etch adhesives were retrieved from the two storage media
      after 3 years and prepared for transmission electron microscopy. RESULTS: Hybrid
      layers from specimens aged in mineral oil exhibited structural integrity of the
      collagen network. Conversely, abnormal hybrid layers were seen in specimens aged
      in artificial saliva, with progressive disintegration of the fibrillar network to
      the extent that it was beyond detection by collagen staining. Self-destruction of
      collagen matrices can occur in resin-infiltrated dentin, and to a lesser degree,
      in mineralized dentin in the absence of bacterial or salivary enzymes.

PMID- 17542206
TI  - Microtensile bond strength of sealant and adhesive systems applied to occlusal
      primary enamel.
AB  - PURPOSE: To compare the microtensile bond strength (muTBS) of a self-etch
      adhesive system (OptiBond Solo Self-Etch Adhesive System), two total etch
      adhesive system (OptiBond FL; OptiBond Solo), and a conventional sealant
      (Clinpro) applied to the occlusal surface of primary molars under saliva
      contamination. METHODS: Sealant and adhesive systems were applied under
      manufacturers' specifications with or without previous saliva contamination.
      After storage in distilled water at 37 degrees C for 24 hours, the specimens were
      longitudinally sectioned perpendicularly to the adhesive interface to obtain
      sticks (0.6 mm2) which were tested under a tensile load of 0.5 mm/minute. The
      bond failure modes were evaluated via scanning electron microscope. Repeated
      measures ANOVA followed by multiple comparisons using Bonferroni's technique was
      used to evaluate the effects of adhesive system and saliva contamination. The pre
      test debonded specimens were included in the computation of the pTBS of each
      tooth. RESULTS: No association between failure mode and the values of muTBS was
      observed (P = 0.3605). The majority of fractures were of mixed type; no cohesive
      failure of enamel or composite resin was observed. No significant effect of
      saliva contamination was detected (P = 0.2044). OptiBond FL and Clinpro had
      equivalent average muTBS (34.5 +/- 2.2 MPa and 45.1 +/- 3.2 MPa, respectively)
      which are significantly higher than the corresponding average muTBS for OptiBond
      Solo Plus and OptiBond Solo SE which may also be considered equivalent (19.1 +/-
      2.3 MPa and 9.8 +/- 2.3 MPa, respectively).

PMID- 17542207
TI  - Fracture strength of restored premolars.
AB  - PURPOSE: To evaluate the fracture resistance (axial compressive strength) of
      premolars restored with different dental materials under two axial loads.
      METHODS: Fracture strength was performed using two metal spheres with 3 mm and 9
      mm diameter. Five restorative techniques were chosen for MOD cavity preparations
      (n = 10): (1) direct resin composite restorations (Z-250); (2) indirect resin
      composite restorations (Z-250 and RelyX); (3) ceramic inlays (Vitadur Alpha); (4)
      conventional amalgam restorations (GS-80); (5) bonded amalgam restorations. The
      restored teeth were compared to human caries-free premolars (Group 6/control).
      Enforce resin cement was used for ceramic and amalgam adhesive restorative
      techniques, according to the manufacturers' instructions. Whenever required, the
      teeth were conditioned by the total etch technique. RESULTS: The ANOVA analysis
      pointed out a significant difference among the groups (P < 0.01) and the "site"
      factor (P < 0.1). The ceramic restorations presented the highest values for
      fracture strength and were similar to the control group. The statistical results
      of direct and indirect resin composite restorations were similar but inferior to
      the control group. The amalgam restorations (conventional and bonded) presented
      the lowest values, with no difference between them. All amalgam groups displayed
      lower strengths when the load was applied on the central fossa (3 mm 0 sphere)
      compared to load applied on cusps (9 mm 0 sphere).

PMID- 17542208
TI  - One-year clinical performance of self-etch adhesives in posterior restorations.
AB  - PURPOSE: To evaluate the 1-year clinical performance of three self-etching
      adhesives (Adper Prompt L-Pop, Clearfil S3 Bond, iBond) in posterior composite
      restorations using one etch&rinse adhesive (One-Step Plus) as control. METHODS:
      Upon approval by the Institutional Review Board, 121 restorations were inserted
      in 38 subjects. The adhesives were applied as per manufacturers' instructions.
      Preparations were restored with a nanofilled resin composite (Filtek Supreme) and
      evaluated at baseline, 6 months, and 1 year. Statistical analyses included the
      Chi-square distribution with the McNemar non-parametric test (P < 0.05). RESULTS:
      At 1 year, 111 restorations in 35 subjects were evaluated using the USPHS
      modified criteria. No significant changes were observed for the etch&rinse
      adhesive One-Step Plus. At 1 year the number of Alfa ratings decreased
      significantly for Clearfil S3 Bond and for iBond in the categories color match,
      marginal staining, and marginal adaptation. For Adper Prompt L-Pop, marginal
      adaptation at 1 year was significantly worse than at baseline. Postoperative
      sensitivity to air improved significantly for Adper Prompt L-Pop, Clearfil S3
      Bond, and iBond. When the evaluation criteria were paired at 1 year, iBond
      resulted in a significantly lower number of Alfa ratings than any of the other
      adhesives for color match, marginal staining, and marginal adaptation. One-Step
      Plus resulted in a greater number of Alfa ratings for marginal adaptation than
      either Adper Prompt L-Pop or Clearfil S3 Bond. Marginal adaptation was
      significantly better for Clearfil S3 Bond than for Adper Prompt L-Pop. The post
      operative sensitivity measured at 1 year for Adper Prompt L-Pop was statistically
      better than that for One-Step Plus.

PMID- 17542209
TI  - Inhibition of enamel demineralization by a bioerodible fluoridated resin.
AB  - PURPOSE: To investigate the efficacy of a bioerodible fluoridated resin on
      inhibition of enamel demineralization. METHODS: Eighteen extracted permanent
      molars were sectioned mesiodistally to obtain 36 caries-free enamel surfaces.
      Each sample was prepared by painting an acid-protective varnish, excluding a 2 x
      8 mm window on either the buccal or lingual surface. The windows of exposed
      enamel were randomly divided into three separate groups (n = 12). Group 1
      received an application of a 5% (by weight) sodium fluoride varnish. Group 2 had
      an experimental 5% sodium fluoride bioerodible resin applied to the window. Group
      3 was left untreated and acted as a control. The samples were then exposed to an
      artificial caries challenge for 17 days, until a visible white spot lesion had
      been created on the control group. The samples were brushed for 1 minute daily.
      Following the acid challenge, the teeth were sectioned longitudinally to obtain
      100 microm sections. Sections were then photographed under polarized light.
      Quantitatively the areas of the lesions were measured by utilizing a computerized
      imaging system. Finally, a comparison was made between mean lesion sizes of the
      sample groups in order to determine their respective efficacy of enamel
      demineralization inhibition. RESULTS: The mean areas (microm)2 of the artificial
      lesions (+/- SD) were: bioerodible fluoridated resin 3,785 +/- 1,794; fluoride
      varnish 7,362 +/- 2,853, and control 11,398 +/- 4,238. ANOVA was performed and
      identified a significant variance (P < 0.001). Tukey's multiple comparison test
      demonstrated that bioerodible fluoridated resin had significantly less enamel
      demineralization than the fluoride varnish and control groups (P < 0.05). The
      fluoride varnish group demonstrated significantly less enamel demineralization
      than the control group (P < 0.05).

PMID- 17542210
TI  - Builders, sprinkler advocates squaring off.

PMID- 17542211
TI  - Learn to let go.

PMID- 17542212
TI  - Of mice and mishaps.

PMID- 17542213
TI  - 7 critical leadership questions.

PMID- 17542214
TI  - Radio check.

PMID- 17542215
TI  - Why be concerned with IAQ?

PMID- 17542216
TI  - Smaller gas detection sensors = smaller gas detectors.

PMID- 17542217
TI  - Where 'industrial' and 'hygiene' join hands.

PMID- 17542218
TI  - Contributions of medical surveillance.

PMID- 17542219
TI  - Disposable FR garments: what are the differences?

PMID- 17542220
TI  - All clear. Laws, codes expanding to help prevent carbon monoxide tragedies.

PMID- 17542221
TI  - Tough cases for the toughest jobs.

PMID- 17542222
TI  - Determining cartridge change schedules.

PMID- 17542223
TI  - After the deluge: outfitting cleanup crews.

PMID- 17542224
TI  - Hazardous chemicals and the importance of eye flushing solutions.

PMID- 17542225
TI  - Tempering emergency equipment water.

PMID- 17542226
TI  - Armed against the heat.

PMID- 17542227
TI  - Q & A: thirst quenchers. Taste does the trick.

PMID- 17542228
TI  - Things everyone should know about machine guarding.

PMID- 17542229
TI  - Organizing to cultivate evidence-based pediatric nursing practice.

PMID- 17542230
TI  - Leisure time activities and obesity in school-aged inner city African American
      and Hispanic children.
AB  - This descriptive-correlational study investigated three research questions: (a)
      What are the leisure time activities (LTA) of school-aged African American and
      Hispanic boys and girls?, (b) What are their body mass index (BMI)
      distributions?, and (c) What relationships exist between total activity scores of
      LTA and BMI in the total sample of children, and for boys and girls analyzed
      separately? The convenience sample consisted of 78 children, aged 9 to 14, who
      were in the fifth to seventh grades of two elementary schools. Children responded
      to a modified version of the Know Your Body Health Habits Survey to assess LTA;
      BMI was calculated based on child height and weight. Results indicated that the
      LTAs of this group of African American and Hispanic children and their
      distribution of BMIs were similar to those of White children, and that no
      appreciable relationships existed between LTAs and BMI in the sample as a whole
      or boys and girls analyzed separately.

PMID- 17542231
TI  - Satisfaction with a school-based teen health center: a report card on care.
AB  - Evaluations of the quality of School-Based Health Center (SBHC) care, both
      satisfaction and outcomes, have been developed by several state SBHC initiatives.
      However, few of these patient satisfaction surveys have been rigorously
      evaluated. An adolescent patient satisfaction based on a grading rubric familiar
      to the adolescents was developed and used to assess care at a nurse-managed teen
      health center. Satisfaction data on 190 encounters were collected in one SBHC
      using a report card rubric. The adolescent patients represented grades 6th
      through 8th, and were almost equally distributed between girls (55.9%) and boys
      (44.1%). This SBHC was a part of a university consortium of nurse-managed
      centers. Results demonstrated high satisfaction (approximately 3.7 out of 4) with
      care using a reliable tool (a = .84) designed for adolescents, which incorporated
      a grading rubric for the evaluation criteria. The nurse practitioner received
      high marks for listening to the students and treating the students with respect.
      Yet, statistical differences by grade level were found. The satisfaction tool was
      found to be reliable (alpha = .84) and consistent with adolescent's perspectives
      on satisfaction with health care. The study is the first published report that
      specifically examined student satisfaction with care in a nurse-managed SBHC.
      Overall satisfaction with care received high "grades" from both first time and
      repeat users, and from boys and girls.

PMID- 17542232
TI  - Shared decision making in school age children with asthma.
AB  - Shared decision making in health care is a mutual partnership between the health
      care provider and the patient. Traditionally, children have had little
      involvement during their medical care visits or in decisions regarding their
      health care. Shared decision making in children with asthma may enhance their
      self-confidence as well as improve their self-management skills. Allowing the
      child to participate during the visit requires assessing the child's competence
      at different ages and abilities. Specific communication techniques to use with
      children during medical encounters include visual aids, turn-taking, clarifying
      communication, and role modeling. Providers additionally can offer strategies to
      parents on how to provide general information about asthma and treatments based
      on the child's questions and interest. The goal for school age children with
      asthma is to change dyadic interactions between the provider and parent into
      triadic interactions to improve the child's asthma management.

PMID- 17542233
TI  - The Bindler-Ball Healthcare Model: a new paradigm for health promotion.
AB  - Nursing of children requires integration of components from many knowledge areas,
      and nurses must consistently plan and carry out interventions to promote health
      and prevent disease and injury for children and adolescents. A new healthcare
      model is applied to child health nursing within all healthcare contexts, from
      acute care settings to chronic care services to well child focused care. Health
      promotion and health maintenance are defined and explored, along with application
      of these concepts in major types of care along the healthcare continuum. The
      influences of family, culture, and community are viewed as integral to health
      promotion strategies. The nurse plans for health promotion and health maintenance
      activities during all acute, chronic, and end-of-life care for youth. The
      healthcare model is a new and creative method in which to frame healthcare for
      children.

PMID- 17542234
TI  - Development of the Child Health Indicator Assessment (CHIA) in a community-based
      nurse-managed center.
AB  - A team comprised of one nurse administrator, three nurse clinicians, and two
      nurse researchers developed the Child Health Indicator Assessment (CHIA), an
      assessment tool that monitors all 10 of the Healthy People 2010 Leading Health
      Indicators in a pediatric nurse-managed practice. The CHIA is a survey to be
      administered in a clinic setting, which facilitates regular health maintenance
      history-taking on 10 key health indicators and provides annual prevalence data on
      the health of one clinic-based population. CHIA Part A solicits parent or
      adolescent self-report data at routine health supervision visits. CHIA Part B is
      completed by a nurse practitioner after the well child visit and includes
      information collected from chart review. The survey development process presented
      several challenges but resulted in an easy-to-use, clinically relevant
      instrument. The data from the CHIA will be used to guide clinic-wide
      interventions to improve and promote pediatric health in two key areas each year.

PMID- 17542235
TI  - Stomach pain.

PMID- 17542236
TI  - Diet and child behavior problems: fact or fiction?
AB  - Dietary treatment of children with behavioral disorders has had wide public
      appeal and been a source of controversy since the 1920's. Yet, to date, there is
      little empirical evidence supporting the effectiveness of dietary restrictions in
      treating child psychiatric disorders, in particular, autism and attention deficit
      hyperactivity disorder (ADHD). Thus, the purpose of this article is (a) to
      provide historical background information regarding dietary treatment in children
      with behavioral disorders, (b) review the evidence-based literature for common
      dietary interventions, (c) discuss limitations in the research, including
      challenges inherent in conducting well-controlled dietary studies, and (d)
      provide recommendations regarding how nurses in primary care settings can assist
      families in making informed decisions.

PMID- 17542237
TI  - The many roles of families in family-centered care--Part III.
AB  - Lawrie Williams, a mother of two daughters who have experienced serious medical
      challenges, authors the third in a series on parental roles in family-centered
      care. This article highlights the role parents can play in helping other families
      through parent-to-parent support programs. Lawrie first experienced the support
      of another parent when one of her daughters was young, and later realized she
      could use her own experiences professionally. For the past 6 years, Lawrie
      Williams has been the coordinator of the Parent Support Program at the Center for
      Children with Special Needs, Children's Hospital & Regional Medical Center in
      Seattle, Washington.

PMID- 17542238
TI  - Prevention and early treatment of overweight and obesity in young children: a
      critical review and appraisal of the evidence.

PMID- 17542239
TI  - Pediatric health care providers' self-reported practices in recognizing and
      treating maternal depression.
AB  - Screening for maternal depression with appropriate intervention has been
      emphasized through pediatric guidelines, but engaging providers to implement such
      procedures remains challenging. This study examined self-reported practice in
      recognizing and treating maternal depression in 98 pediatric health care
      providers. Over 85% agreed that recognizing maternal depression was their
      responsibility, yet only half reported confidence in their ability to do so.
      Fewer than 10% reported asking mothers about depression or using a screening
      tool. Clear differences in practice, treatment, and perceived barriers by
      confidence level were found. Implications for practice, research, and training
      are discussed.

PMID- 17542240
TI  - The Ashley treatment: two viewpoints.

PMID- 17542241
TI  - Environmental exposure assessment, pollution sources, and exposure agents: a
      primer for pediatric nursing professionals.
AB  - Children's environmental health is a growing, interdisciplinary field of diverse
      professionals and community members working together in policy advocacy,
      research, health, and environmental interventions and treatment services.
      Understanding exposure assessment is central to improving children's health
      across age, gender, indicators of socioeconomic status, and racial/ethnic groups.
      In general, children are more susceptible and vulnerable to adverse acute and
      chronic effects due to acute and chronic exposures to environmental toxicants
      since they eat more food, drink more fluids, and breathe in more air per unit of
      body weight than adults; their behaviors and rapid developmental changes also
      contribute to their risks. By enhancing knowledge and awareness of the basic
      concepts of human exposure assessment and key details of sources of environmental
      pollution, pediatric nursing professionals can enhance their practices--clinical
      and patient education skills--and thus improve daily work in their communities
      through the promotion of exposure reduction or prevention measures.

PMID- 17542242
TI  - Letter regarding "The many roles of family members in family-centered care: Part
      1".

PMID- 17542243
TI  - [Assessment of the knowledge of GINA in physicians of different levels of
      attention].
AB  - BACKGROUND: Asthma has a growing prevalence all over the world. GINA guidelines
      had improved diagnostic and therapeutic asthma approach, but it is not enough.
      OBJECTIVE: To evaluate the knowledge about GINA in physicians of first, second
      and third care level. PARTICIPANTS AND METHODS: Physicians working in first,
      second and third care level, from medical units related to the Centro Medico
      Nacional La Raza answered a 19 items questionnaire about GINA. Results were
      analyzed with Kruskal-Wallis, Pearson's correlation and U of Mann-Whitney tests.
      RESULTS: We included 179 physicians with an age average of 43 years; 99 or them
      were 99 females and 80 males. According to medical specialty, Allergy and
      Immunology had 145 points; Pneumology, 136; Pediatrics, 122; Family Medicine, 81
      and Internal Medicine, 78. We found a statistical difference between these
      specialties (p < 0.0001). Doctors from third and second care level had a higher
      and significative scoring than first care level colleagues (p < 0.005). We did
      not find differences between labor years, working schedule and gender with GINA
      knowledge scoring. CONCLUSIONS: There are differences in GINA knowledge between
      medical specialties and care level.

PMID- 17542244
TI  - [Anaphylaxis and anaphylactic shock].
AB  - Term anaphylaxis means an immediate hypersensitivity reaction mediated by IgE
      that produces a clinical syndrome with systemic affection of variable severity.
      Its prevalence varies according to the habits of each region and of the studied
      population from 3.2 to 7.6 cases per 100,000 inhabitants per year. Anaphylaxis
      secondary to the food ingestion accounts for 30-50% of the cases. Some risk
      factors have been defined, among them the most important are asthma, food allergy
      and previous reactions to the same food. Biphasic anaphylactic reactions are
      those presenting a recurrence of anaphylactic symptoms, after the initial
      remission of them. Success of treatment is based on the early recognition of
      signs and symptoms and the instauration of treatment with adrenaline.

PMID- 17542245
TI  - [Allergic conjunctivitis in children].
AB  - Allergic conjunctivitis is a group of diseases that are frequent in childhood,
      associated to several allergic diseases affecting the ocular surface. It is
      related to type 1 hypersensitivity reactions. Two acute disorders: seasonal
      allergic conjunctivitis and perennial allergic conjunctivitis, exist, as do three
      chronic diseases: vernal keratoconjunctivitis, atopic keratoconjunctivitis and
      giant papillary conjunctivitis. The ocular surface inflammation causes itching,
      tearing, lid and conjunctival edema-redness, and photophobia during the acute
      phase and can lead to a classic late-phase response (associated to eosinophilia
      and neutrophilia) in a subset of individuals. As in the case of several chronic
      allergic diseases, it can remodel the ocular surface tissue. This allergic
      disease is very frequent. Vernal keratoconjunctivitis could produce corneal
      lesions and visual illness; however, atopic keratoconjunctivitis does not
      permanently affect the vision. The aim of this review is to provide a current
      overview for a better understanding of the symptoms associated to this disease,
      to describe its classification, recent advances in its physiopathology and its
      treatment.

PMID- 17542246
TI  - [Urticaria and angioedema].
AB  - Urticaria is considered a heterogeneous group of diseases that share different
      patterns of skin reactions. The wide diversity in urticaria subtypes have been
      identified and this reflects partial understanding of the causes or factors that
      trigger it, as well as the molecular and cellular mechanisms that are involved in
      their physiopathology. The objective of this article was to make an extensive
      review of the literature to be able to offer the readers a complete information
      and updating on the basic, ethiologic and physiophatologic mechanisms and mainly
      to make a special emphasis on diagnosis and treatment of urticaria, promoting the
      continuous medical education.

PMID- 17542247
TI  - [Peripheral anticholinergic syndrome].
AB  - This is a case report of a woman of 38 years old, studied and analyzed at the
      service of allergy and immunology with clinical manifestations of allergic
      rhinitis; studies of laboratory, cabinet and intradermal test were made to
      corroborate this diagnosis and the treatment with specific hyposensitization,
      oral antihistaminines and inhaled steroids was started. Two years later the
      patient referred urinary retention without important antecedents, so, a
      peripheral anticholinergic syndrome (PAS) was suspected, a urodynamic test study
      was carried out consisting in a uroflujometry, static and dynamic urethral
      profile, cystometry, flow pressure study and electromyography, which diagnosed
      low urinary obstruction (functional) and vesical sphincter pseudodysfunction,
      demonstrating the PAS associated with oral antihistamines.

PMID- 17542248
TI  - [Treatment of asthmatic patients with zafirlukast].
AB  - BACKGROUND: Asthma is a chronic inflammatory illness of the airways in which
      several cells intervene playing an important role in the development of the
      bronchial hyperreactivity. Leukotriens are mediators that participate in the
      inflammatory process. OBJECTIVES: To value the effectiveness of the zafirlukast
      in patients with persistent moderate and severe asthma, and to investigate the
      undesirable effects and the symptoms of intolerance in the study group. PATIENTS
      AND METHODS: The study was carried out on 103 moderate and severe persistent
      asthmatic patients, with ages between 15 and 50 years, without antecedents of
      haematological, hepatic or renal diseases, who received 20 milligrams of
      zafirlukast twice daily during one year. The monitoring was done every month
      based on its clinical evolution, with control of the renal and hepatic function
      at the beginning, at six months and at the end of the study. Tests of respiratory
      function were made at the beginning and the end of the treatment. CONCLUSIONS:
      The results show the effectiveness of this medicine, without problems of
      intolerance or other important secondary adverse effects.

PMID- 17542249
TI  - [High-affinity C-reactive protein as inflammatory marker].
AB  - ANTECEDENTS: Non-immunological and immunological diseases have been reported to
      present a level of serum C-reactive protein (CRP) higher than the base level. For
      both, this level can guide the diagnosis and prognosis. OBJECTIVE: To test the
      value of serum CRP, by a high-sensitivity CRP assay, during a non-immunological
      disease, in order to understand if this level is significant during the non
      immunological diseases. PATIENTS AND METHODS: In this study, 50 patients were
      divided in two groups according to different specific illness: 25 patients with
      unstable angina (UA) and 25 with acute myocardial infarction (AMI) with and
      without metabolic syndrome associated. Plasmatic CRP measurement was made for
      every patient, following an immunoturbidimetric high affinity technique performed
      in a RX Daytona clinical chemistry analyzer by Randox. Statistical comparison of
      the serum CRP level between groups was done using a Student's t-test. An ANOVA
      test was used to value cardiovascular risk factors associated with the serum CRP
      level. A p < 0.05 was considered to be significant. RESULTS: To each illness,
      patients were classified into five subgroups, based on their plasmatic CRP level:
      0.014 to 3.9 mg/L, 4 to 7.9 mg/L, 8.0 to 11.9 mg/L, 12 to 14.9 mg/L, and higher
      than 15 mg/L. Patients with UA were 16 (64%), 2 (8%), 0 (0%), 5 (20%), and 2
      (8%), respectively. And patients with AMI were 15 (60%), 3 (12%), 4 (16%), 3
      (12%), and 0 (0%), respectively. Statistical tests performed did not have
      significant difference. CONCLUSIONS: We have proved that the serum CRP level,
      determined by a high-sensitivity CRP assay, can be useful in early detection of
      inflammatory processes in immunological and non-immunological diseases.

PMID- 17542250
TI  - [Neumopathies in patients with primary immunodeficiencies in treatment with
      intravenous gammaglobulin].
AB  - BACKGROUND: The primary immunodeficiency diseases cause a deficit in the
      production of antibodies. The chronic sinopulmonary disease is common and their
      clinic symptoms are diverse (pneumonia, bronchiectasis). OBJECTIVE: To know the
      frequency and type of pulmonary abnormalities in patients with primary
      immunodeficiency in treatment with intravenous immunoglobulin. MATERIAL AND
      METHODS: 24 files of patients with primary immunodeficiency were selected. Age,
      sex, primary immunodeficiency type, time of immunoglobulin treatment, chest X-ray
      finding, pulmonary computed tomography of high resolution (HRCT) and pulmonary
      function tests were registered. Measures of central tendency were calculated.
      RESULTS: There was no predominance of gender; the average age was 14 years old.
      The common variable immunodeficiency and the Bruton's hypogammaglobulinemia
      represented 91% of the patients. The X-ray of thorax was abnormal in 33%,
      although there were not bronchiectasis. The high-resolution computed tomography
      scan (HRCT) was abnormal in 67%, and 75% had bronchiectasis. CONCLUSIONS: The
      pulmonary complications are common despite therapy with intravenous
      immunoglobulin. The HRCT is better than X-ray in these patients.

PMID- 17542251
TI  - [Prevalence of atopic dermatitis in 6-14 year old children in Morelia, Michoacan,
      Mexico].
AB  - BACKGROUND: Atopic dermatitis is a frequent chronic dermatosis in children.
      OBJECTIVE: To determine the prevalence of atopic dermatitis in a pediatric
      population from Morelia, Michoacan. PARTICIPANTS AND METHODS: An observational,
      descriptive and comparative study was done to estimate the prevalence and
      underdiagnosis of atopic dermatitis in children and teenagers from Morelia,
      Michoacan (n=9578). This study had a sensitivity of 0.87 and a specificity of
      0.92. RESULTS: A prevalence of 10.1% and 5.4% was found in children from 6 to 10
      years old and teenagers from 11 to 16 years old. The diagnosis was done in only
      20% of all cases. The high underdiagnosis suggests taking emergent actions of
      preventive medicine. CONCLUSIONS: The prevalence of atopic dermatitis in
      pediatric population from Morelia is similar of that reported in the United
      States and less than of Mexico City.

PMID- 17542252
TI  - [Asthma and obesity: related inflammatory diseases].
AB  - Asthma and obesity are diseases that have increased their prevalence parallely in
      the last years, becoming health problems in our country. Asthma is a chronic
      inflammatory disease and in the last years obesity has also been catalogued as a
      systemic inflammatory disease considering that adipose tissue is an endocrine
      organ that produces cytokines that can promote severity of asthma; therefore
      generating interest in the investigators to perform studies that can relate both
      conditions.

PMID- 17542253
TI  - [Analysis of death maternal cases during a 10-year period].
AB  - OBJECTIVES: To determine the clinical features, as well as to present an analysis
      of the cases of maternal death during a period of ten years. PATIENTS AND
      METHODS: A descriptive, transverse, retrospective and cases series research was
      carried out. There was a revision of the expedients of maternal death occurred at
      the Regional General Hospital number 36 in Puebla, from January 1st, 1996 to
      December 31st, 2005. They were selected the patients who passed away because of
      obstetric death. The data collection included the following variables: age, body
      mass index, education, number of gestations, type of labour, prenatal control,
      basic cause of dead, and the month and the year in which it occurred. The
      descriptive statistics was used with central tendency and dispersion
      measurements. RESULTS: 75 maternal deaths were registered; one of them was
      excluded because it was not an obstetric cause. The maternal death rate was 63.46
      per 100,000 born alive. The 17.5% corresponded to indirect obstetric causes and
      82.5% to direct obstetric causes; the 73% were preventable, 27% were no
      preventable. Forty-eight cases corresponded to ages between 21 and 34 years.
      Forty-six cases corresponded to mothers with 2 to 4 pregnancies. In 43 cases they
      had a level of education which ranks between elementary and junior high school.
      In 31 cases they had a body mass index of 21 to 26. The eclampsia was the cause
      of maternal death in 20 cases and the obstetric haemorrhage in 16 cases. There
      were appropriate prenatal controls in 38 cases. CONCLUSIONS: The maternal death
      cases corresponded to an average age women, multigravidas, no obese, and
      apparently appropriate prenatal control. During this period there was a tendency
      to the decrease of obstetric haemorrhage and an increase of the preeclampsia
      eclampsia as causes of maternal death.

PMID- 17542254
TI  - [Correlation between clinical characteristics and mycological tests in the
      vulvovaginitis by Candida].
AB  - BACKGROUND: Vulvovaginitis caused by Candida sp is one of the most frequent
      infections. OBJECTIVES: To culture and to identify the fungi related to clinical
      manifestations of patients based on a suspected diagnosis of vulvovaginal
      candidiasis. PATIENTS AND METHODS: A prospective, transversal and comparative
      study was performed on 181 women older than 18 years with vulvovaginitis by
      Candida sp. A correlation was made between the clinical characteristics of this
      entity and mycological tests such as direct examination and cultures. RESULTS:
      The direct exam or fresh vaginal exam and cervical sample was positive for the
      different microscopic forms of Candida (blastoconidia, pseudohyphye or
      pseudomycelia) in 60.8% (110 women); at the same time that cultures were positive
      for Candida sp in 51.9% (94 patients). CONCLUSIONS: The direct examination and
      the cultures of vaginal and cervical exudate are mandatory tests for diagnosis of
      Candida sp in women with vulvovaginitis.

PMID- 17542255
TI  - [Irregular secretion of prolactin in infertile women with normoprolactinemic
      galactorrhea].
AB  - BACKGROUND: Abnormal frequency and pulse amplitud of prolactin secretion in micro
      and macroprolactinomas has been atributed to a dysfunctional tumoral lactotrope.
      Previous evidence suggests that non tumoral hyperprolactinemia is caused by a
      hypothalamic dysfunction. The regularity of prolactin secretion has not been
      studied with cuantitative methods in patients with normoprolactinemic
      galactorrhea (NPG) which could be considered an entity that precedes non tumoral
      and tumoral hyperprolactinemia. OBJECTIVE: To analyze the 24-hour prolactin
      secretion pattern and its secretion regularity in a group of infertile women with
      normoprolactinemic galatorea. PATIENTS AND METHODS: A transversal-comparative
      study was carried out in 6 infertile women with normoprolactinemic galactorrhea
      and 4 healthy women as controls. The 24 hour prolactin profile, the ratio night
      time mean concentration/daytime mean concentrattion (NM/DM ratio) and apparent
      entropy (Ap En, Ap En ratio) were compared in the two groups. RESULTS: Blunting
      of the nyctohemeral rythm and nocturn hyperprolactinaemia occurred in patients
      with normoprolactinemic galactorrhea (NPG). NM/DM ratio was lower in patients
      with NPG than in controls (1.28 +/- 0.25 vs. 1.75 +/- 0.05; p= 0.01). Higher
      irregularity of prolactin secretion was found in patients with NPG (ApEn: 0.853
      +/- 0.158 vs 0.608 +/- 0.171, p=0.04; Ap En ratio: 0.839 +/- 0.11 vs 0.661 +/-
      0.14; p=0.04). CONCLUSIONS: The irregularity of prolactin secretion in patients
      with NPG is not dependant on the presence of a pituitary tumour which suggests
      that a hypothalamic dysfunction underlies this condition. An irregular secretion
      and a higher daily mass production of prolactin in patients with NPG could
      explain both galactorrhea and infertility.

PMID- 17542256
TI  - [Medical-social characteristics of maternal deaths in a Mayan community of
      Yucatan, Mexico].
AB  - OBJECTIVE: To describe clinical and sociodemographic characteristics of maternal
      deaths occurred from 1997 to 2001, so as the access and availability of services
      of health, in the municipality of Chemax, Yucatan, Mexico. MATERIAL AND METHODS:
      Acts and certificates of death of women born in the municipality of Chemax were
      reviewed. The maternal deaths were classified in direct and indirect obstetrical
      deaths, according to criteria of the International Statistical Classification of
      Diseases and Related Health Problems (tenth revision). The knowledge of the women
      on risks in the pregnancy, childbirth and the postpartum period was explored
      indirectly in the relatives, as well as perceptions of these last ones on the
      death. The time passed between the search of aid and the attention was
      calculated. RESULTS: Nine cases of maternal deaths were registered during 1997
      2001 period, two of which were findings of the study. The principal cause was the
      obstetric hemorrhage. The 9 women spoke Mayan an 5 understood in addition the
      Spanish. The women did not know the obstetrical risks. The perceptions of the
      relatives on the deaths were bound to myths, lack of information and medical
      attention. The minimum time of transfer for the attention of the childbirth was
      of 10 minutes and the maximum of 2 hours. For the attention of the complications,
      eigth women were transferred to a hospital outside their locality. CONCLUSIONS:
      The hemorrhage postpartum was the leading cause of maternal death in Chemax.
      Sociodemographic factors and of access to the health services, characterized to
      the maternal deaths in this community. Something similar could be happening in
      other communities very marginalized of Yucatan.

PMID- 17542257
TI  - [Perception of gyneco-obstetric physicians about hormone replacement therapy].
AB  - OBJECTIVE: To identify which is the medical perception of the gynecology
      obstetric physicians (Ob-Gyn's) according to hormone therapy (HT) after WHI
      trial. MATERIAL AND METHODS: 104 Ob-Gyn were interrogated, and divided into 5
      groups according to their position in the hospital. Descriptive statistics was
      used and the comparisons were done with Student's t test. RESULTS: 31.7% of the
      interviewed were in the fifth decade of life and 71% were male. 93.6% referred
      that HT might not be used in postmenopausal women older 50 years age. Most of
      them considered that HT decreases osteoporosis and depression. 90.4% considered
      that HT must be used premature menopause. 91.3% prescribed progestagens in
      patients with uterus. Oral route was preferred by 50% and the transdermic in
      30.8%. 80.8% referred that combined HT did not increase the possibility of
      endometrial cancer but it did for breast cancer (71.2%). In the same way they
      considered that improved vaginal lubrication (95.2%), mood (87.5%), hot-flushes
      (92.3%) and menstrual disturbances (80.8%). 95.2% considered that HT improves
      quality of life. 62.5% referred that WHI trial modified the way they prescribe
      HT. 80.8% considered that low dose HT is as good as conventional dose HT.
      CONCLUSIONS: This interview permitted to know the opinion in relation to HT,
      without difference between the interviewed and world tendency.

PMID- 17542258
TI  - [Evidence-based obstetric conduct. Severe preeclampsia: aggressive or expectant
      management?].
AB  - In severe preeclampsia, delivery is assisted immediately without thinking in
      fetal conditions. Some decades ago, there is agreement to hospitalize, but there
      is no agreement between expectant or aggressive management. Here are revised
      these two management evidence based medicine. Fifteen non randomized non
      controlled trials in English and 4 in Latin American literature highlight 10-14
      days pregnancy prolongation without increase maternal morbidity with conservative
      management; but there were criticized by non random patient selection and non
      controlled. Two randomized controlled trials showed improvement in neonatal
      results with no change in maternal, with expectant management. One systematic
      review of these two trials concluded there is not sufficient data to any reliable
      recommendation and proposes longer trials are necessary. In United States,
      National Working Group in the High Blood Pressure Educational Program believes
      expectant management is only possible in selective women group between 23-32
      weeks. The American College of Obstetricians and Gynecologist recommends this
      management in a tertiary care setting or in consultation with an obstetrician
      gynecologist with training in high risk pregnancies. Expectant management present
      proposal in severe preeclampsia remote from term is summarized.

PMID- 17542259
TI  - [Giant chorioangioma and its perinatal complications. A report of a case].
AB  - It is presented a clinical case of a pregnant patient, who attended to the
      hospital's emergency service because of the presence of transvaginal liquid. A
      polyhidramnios was diagnosed, due to a placental chorioangioma (of approximately
      7 cm), which was confirmed by hystopatological examination, reporting placental
      chorioangioma with its three histological types: cellular, angioblastic and
      degenerative. The case and its complications, such as polyhidramnios, membranes
      rupture and preterm labor, are analized. Existing literature is reviewed.

PMID- 17542260
TI  - [Benign peritoneal cystic mesothelioma as differential diagnose of an ovarian
      dependant tumor. Case report and review of the literature].
AB  - Benign cystic mesothelioma is an uncommon lesion of the peritoneum, occurring
      predominantly in women of reproductive age. The present case is a multitreated
      perimenopausal woman with lower urinary tract symptoms without clinical
      improvement despite the treatment, and pelvic pain with physical findings and
      radiology studies of a probable ovarian mass dependant tumoration, requiring
      protocolized exploratory laparotomy, finding a benign cystic mesothelioma.
      Despite the low incidence of this tumoration the gynecologist must be familiar
      with this disease, because of the high recurrence. Nowadays, steroid hormone
      receptors typification seems to play an important role to control the recurrence
      of this tumoration.

PMID- 17542261
TI  - [Common vaginal infections. 1952].

PMID- 17542262
TI  - [Fetal weight estimation in children of diabetes mellitus mothers].
AB  - BACKGROUND: Pregnancy-associated diabetes mellitus poses a risk of fetal growth
      alterations. Fetal abdominal perimeter can be predictive of weight in full-term
      fetuses with normal growth, along with biparietal diameter, cephalic
      circumference, abdominal circumference and length of femur. OBJECTIVE: To
      estimate fetal weight through set parameters. PATIENTS AND METHODS: A descriptive
      correlational research was done, with study of the biometric parameters of fetal
      weight estimation during the third trimester of gestation of 59 diabetic pregnant
      patients, who were studied in the University of Carabobo's Diabetes and Pregnancy
      Unit and Perinatology Unit at the Enrique Tejera Hospital City in Valencia,
      Venezuela, 2004. RESULTS: Sixty-four percent had gestational diabetes mellitus,
      24% diabetes mellitus type 2, and 12% diabetes mellitus type 1. Serial ultrasound
      scans were performed on 33 women during the three trimesters of pregnancy, and to
      16, it was performed another ultrasound scan one week prior to delivery or
      cesarean section, for fetal weight estimation. Gestation mean time was 37.5 +/-
      0.51 weeks. Average estimated fetal weight was 3555.87 +/- 455.41 g. Kolmogorov
      Smirnov normalcy tests: 0.200 (estimated fetal weight), 0.116 (birth weight),
      0.000 (assessment week). T test: -0.506 Sig: 0.620 p > 0.05. Estimated fetal
      weight/birth-weight correlation: Pearson: 0.749 Sig. 0.001 < 0.005, r: 0.749,
      r2:0.561, F: 17.870 Sig: 0.001 < 0.05, thus demonstrating that correlation does
      exist. Prediction: newborn weight: 95.2 +/- 0.987 (estimated weight). CONCLUSION:
      Estimated fetal weight at the end of the third trimester constitutes a good
      predictive parameter of fetal weight in newborn of diabetic mothers.

PMID- 17542263
TI  - [Reproductive risk factors of breast cancer in patients attended at a second
      level urban hospital].
AB  - OBJECTIVE: To evaluate the implication of reproductive risk factors for breast
      cancer of patients at a breast clinic of a second level urban hospital. PATIENTS
      AND METHOD: Women with breast cancer and randomly selected age-matched control
      subjects were evaluated. Age, age of menarche and menopause, age of first full
      term pregnancy, number of pregnancies, lactation, family history of breast cancer
      and family history of other cancers were analyzed. RESULTS: Sixty-six cases with
      breast cancer and 132 controls were study. Cases were older at first full term
      pregnancy (25.8 +/- 6.4 vs 23.3 +/- 5 years old, p = 0.01) and presented
      frequently first full term pregnancies after 30 years old (19.6 vs. 6%, p =
      0.01); these differences also were significative for cases of 50 years or older.
      Cases younger than 50 years old had short lifetime lactation (11.5 +/- 8.2 vs. 27
      +/- 30 months, p < 0.001), and few presented lactation longer than 12 months
      (27.8 vs 55.8%, p = 0.02). CONCLUSIONS: In this research the most important
      breast cancer risk factor for women older than 50 years old was the age of first
      full term pregnancy. For women younger than 50 years old periods of lifetime
      lactation shorter than 12 months seems a risk factor.

PMID- 17542264
TI  - [Causes of preterm delivery among adolescent mothers].
AB  - OBJECTIVE: To describe the proportion of preterm delivery at pregnant adolescents
      clinic and their maternal, obstetric and fetal conditions other than spontaneous
      labor. PATIENTS AND METHOD: Descriptive inside a cohort of consecutive cases.
      Preterm was defined from 20 to 36 full weeks. Maternal, obstetric and fetal
      conditions were defined if directly caused preterm labor or elective
      interruption; it was differentiated from spontaneous preterm labor. RESULTS:
      Preterm delivery rate was 10.8% (252/2326): 0.8% from 20 to 27 weeks (19/2326),
      3.3% from 28 to 33 weeks (77/2326) and 6.7% from 34 to 36 weeks (156/2326).
      Spontaneous preterm labor presented in 39.3% (99/252); main conditions found
      were: rupture of the membranes 18.7% (47/252), preeclampsia-eclampsia 10.3%
      (26/252), twin pregnancy 10.3% (26/252), intrauterine growth restriction 5.6%
      (14/252) and congenital defects 5.6% (14/252). They were classified as: obstetric
      type 34.9% (887252), fetal 25.4% (64/252) and maternal 0.4% (1/252). There was a
      40.5% rate of vaginal delivery (102/252), with the use of forceps in 1 out of 5.
      CONCLUSIONS: At purpose-built clinics using evidence-based and problem oriented
      interventions, that are individually adapted and continuously up-dated, a non
      risk comparable preterm delivery rate can be achieved at gestational ages with
      better neonatal prognosis.

PMID- 17542265
TI  - [Practices in the care of the low-risk delivery in hospitals in southern Chile].
AB  - BACKGROUND: A relevant component to achieve high quality of care is the
      implementation of evidence based practices. OBJECTIVE: To assess in two
      maternities in the South of Chile, the use of evidence based practices in labour
      and delivery care. PATIENTS AND METHODS: In two hospitals, 205 women after
      delivery were interviewed. Eleven forms of care were selected from the
      classification provided by the WHO Reproductive Health Library, four as
      beneficial forms of care and seven as forms of care likely to be harmful.
      RESULTS: Beneficial forms of care were used between 17 to 46% and forms likely to
      be harmful between 17 and 98%. No association among the use of the practices and
      some maternal characteristics, such as age, parity and years on school, were
      found. Women interpretation about benefits of the practices is not in agreement
      with the evidence provided by the trials. CONCLUSIONS: A low adherence to
      evidence based practices was observed since some practices of proven benefit are
      poorly used and many practices likely to be harmful are highly used. There is a
      need to look for strategies aimed at the better use of evidences based practices
      considering among these strategies women empowerment.

PMID- 17542266
TI  - [Vesicovaginal fistula. Experience at the Instituto Nacional de Perinatologia].
AB  - BACKGROUND: The damage of the lower urinary tract is originated by complications
      of obstetric or gynecological surgery, which if not detected timely determines
      the formation of fistulas. OBJECTIVE: To analyze the experience in diagnosing and
      treating vesicovaginal fistulas attended at the gynecologic urology clinic of the
      Instituto Nacional de Perinatologia (INPer). MATERIAL AND METHOD: Retrospective
      study of 27 files of patients diagnosed with vesicovaginal fistula at the
      gynecologic urology clinic of the INPer from January 11 1992 trough December 31st
      2005. The variables analyzed were age, parity, corporal mass index, surgical
      history, surgery performed to correct the fistula and postoperative evolution.
      Averages and standard deviation were calculated to describe data. RESULTS:
      Average age was 38.2 years. Abdominal hysterectomy (53.3%), followed by obstetric
      hysterectomy (33.3%), caused the most of complications. The most often used
      techniques to correct the fistula were Latzko operation, 19 patients (45.23%),
      and Sims' fistulectomy, 11 patients (26.19%). The most used drainage was Foley
      probes, with 9.1 days average of use. Urinary tract infection was the most common
      complication (6.7%). CONCLUSIONS. After our analysis, surgical treatment to
      patients with vesicovaginal fistula showed good results (71.4% of healing) with a
      minimum of complications (28.5% of recurrence).

PMID- 17542267
TI  - [Advances in hormonal contraception].
AB  - This review provides an update regarding newer options in hormonal contraception
      that include the progestin-releasing intrauterine system, the contraceptive patch
      and ring, the single rod progestin-releasing implant, extended and emergency oral
      contraception and recent advances in hormonal male contraception. These methods
      represent a major advancement in this field, allowing for the development of more
      acceptable, safety and effective birth control regimens.

PMID- 17542268
TI  - [Gastric wall in benign cystic teratoma of the ovary].
AB  - We present the clinicopathlogical features of an ovarian mature cystic teratoma
      with a fully developed gastric wall containing an extensive peptic ulcer.
      Complete gastric wall, was the only teratomatous tissue present. There are only
      two previous reported cases of gastric mucosa with a peptic ulcer in an ovarian
      teratoma.

PMID- 17542269
TI  - [Fertility and testicular function in a patient with germ cell extragonadal
      tumor. A report of a case].
AB  - Males are affected from primary extragonadal germ cell tumors with a frequency of
      2 to 5%. There is a high incidence of infertility of more than 60% and most of
      the cases have azoospermia due to testicular damage. The hormonal profile of
      these patients shows normal luteinizing hormone, normal follicle stimulating
      hormone and normal testosterone and estradiol. We communicate the case of a male
      who had a primary retroperitoneal germ cell tumor with a low title of chorionic
      gonadotropin, elevated estradiol and normal testosterone, prolactin and
      seminogram. Before beginning treatment with chemotherapy, his wife became
      pregnant delivering twins, both males. The patient was treated with chemo and
      radiotherapy after which he became azoospermic with an increase in both
      luteinizing hormone and follicle stimulating, decreased levels of estradiol and
      without alteration in prolactin and testosterone. The pituitary testicle axis was
      affected by the tumor, but the microenvironment of the testicles did not seem to
      be damaged only after initiating treatment.

PMID- 17542270
TI  - [The Robert B. Greenblatt, M. D. Library at the Medical College of Georgia].

PMID- 17542271
TI  - [Candida--adolescence. Commensalism or infection. Approaches to an underestimate
      problem on the increase].

PMID- 17542272
TI  - [Problems of male sterility. 1952].

PMID- 17542273
TI  - [Surgical treatment of hemorroids with rectal mucosal resection using a stapler].
AB  - OBJECTIVE: To analyze the results of Longo stapled mucosectomy for hemorrhoidal
      disease in a 1 to 3 years follow up. PATIENTS AND METHODS: Clinical response and
      complications where analyzed in patients treated for grade II to IV non
      complicated hemorrhoidal disease with Longo stapled hemorrhoidectomy. RESULTS: In
      a 27 months period, 160 patients were treated (105 men and 55 women), mean age
      was 44.1 years (range: 24 to 72 years), and 110 patients had grade III hemorrhoid
      disease. Non procedure complications were noted, early complications were
      detected in 5% of patients and late complications were detected in 10% of
      patients. In a mean follow-up of 18.8 months, 82.5% of the patients remained
      asymptomatic and 94.4 of the patients reported a good satisfaction score. A
      second surgery was required in three patients because of recurrence. CONCLUSION:
      Longo stapled mucosectomy is a safe treatment for non complicated hemorrhoid
      disease. In a 18 month follow up most patients were asymptomatic.

PMID- 17542274
TI  - [Hemorroidal disease in a specialty medical center].
AB  - BACKGROUND DATA: Haemorrhoids and the symptoms they produce have been recorded
      throughout history. This disease affects 4-10% of the population. The treatment
      is based on the degree of haemorrhoidal prolapse and the severity of symptoms.
      OBJECTIVES: The aim of this study is to show our experience in the treatment of
      haemorrhoidal disease in the colorectal surgery department from the Centro Medico
      Nacional Siglo XXI, (IMSS, Mexico, D.F). METHODS: Clinical files were reviewed of
      patients treated by surgical procedures in a period from March 1996 to March
      2004. RESULTS: 3,304 medical consultations were given to first time patients; 443
      patients were diagnosed with haemorrhoidal disease representing 13.4% of the
      anorectal pathology: 358 patients underwent an anorectal operation, 225 males
      (62.8%) and 133females (37.2%), mean age of 48 years (range 18-78 years). The
      principal symptoms were bleeding and pain. We found another associated pathology
      in 20% of the cases. 46 patients were affected by second degree haemorrhoids
      (12.8%), 244 third degree (68.3%) and 68 patients by fourth degree (19%). The
      Ferguson technique was the most used (84%). At the same time as the
      haemorrhoidectomy we did other anorrectal procedures in 20% of patients. The mean
      operation time was 53 minutes (range 19-150). Acute urinary retention occurred in
      28 patients (8%) leak sutures in seven (2%), and bleeding in six (1.7%). The mean
      hospital stays were two days with follow up of 42 days. The total morbility was
      4.7%. CONCLUSIONS: The incidence of haemorrhoidal disease in this study was
      13.4%. 80% ofpatients were treated by surgery. This pathology is more common in
      the fifth decade of life with male-female relation of 1. 7:1. The acute urinary
      retention was the most common complication. During the performing of a
      haemorrhoidectomy it was possible to resolve other anorectal pathologies. The
      Ferguson technique was the most used with a total morbility of 4.7%.

PMID- 17542275
TI  - [Open acess to endoscopy in a tertiary referal center].
AB  - OBJECTIVE: The purpose of this study was to determine the yield of open access
      endoscopy in a third level Mexican hospital. BACKGROUND DATA: Open access
      endoscopy is common in United States of America and Europe (endoscopy is
      performed without prior specialist consultation). In Mexico this system hasn't
      become popular yet. The usefulness of open access endoscopy has been questioned.
      Some indications for upper gastrointestinal endoscopy (UGE) aren't included in
      the guidelines for appropriate use of endoscopy. METHOD: All patients referred to
      diagnostic UGE in our hospital were admitted during a period of 30 days. The
      indications of UGE were analyzed by means the American Society of
      Gastrointestinal Endoscopy (ASGE) guidelines for the appropriate use of upper
      gastrointestinal endoscopy. Relevant findings were analyzed to all UGE performed
      in the study. RESULTS: The mean age of the 208 patients studied was 52.5 years;
      169 UGE (81.2%) were appropriated according to the ASGE guidelines. Seventy-five
      percent of appropriate UGE had relevant findings compared with 59% of
      inappropriate UGE (p < 0.05). There wasn't difference when compared the rate of
      relevant findings in appropriate UGE (75%) with 72% in all UEG performed. Ten
      patients had indications that didn't fit in the ASGE guidelines. CONCLUSIONS: The
      appropriate EGDs have more relevant findings but the inappropriate EGDs have an
      important number of relevant findings too. The ASGE guidelines are not always
      suitable for all patients. This study supports the usefulness of open acces
      endoscopy.

PMID- 17542276
TI  - [Prevalence and risk faactors of Helicobacter pylori infection in three
      populations of children in Puebla, Mexico].
AB  - INTRODUCTION: The infection by Helicobacter pylori affects approximately 50% of
      the world population, in average, nevertheless the geographical area and the
      socioeconomic conditions are determining for the infection in earlier ages, not
      even that, only 20% of these patients will develop gastroduodenal disease. The
      infection is distributed universally, concerning more to the countries in routes
      of development, where he appears with major frequency in the infantile and young
      population. In Mexico the seroprevalence studies founded that 20% of the children
      of one year old already had developed antibodies Ig G against Helicobacter pylori
      and 50% of them are positive 10 years after The major prevalence is reached
      between 25 and 30 years of age. In our community we do not know the prevalence of
      active infection. MATERIAL AND METHODS: The study group became from three
      different communities: Group A. Formed with children from half-low socioeconomic
      level, which they come habitually to a school placed in the conurban zone of the
      city of Puebla, Mexico and that inhabit a marginal area of asistential services
      of sanitary attention. Group B. Formed with children from the rural zone, of
      socioeconomic rural way, which habitually they come to a school placed in the
      surroundings of the City of Puebla, Mexico and that live in a rural zone, with
      regular services of sanitary attention. Group C. Formed with children from high
      socioeconomic level, which they come habitually to a private school placed in the
      city of It Populates, Mexico and that inhabit in zones with all the sanitary
      services. RESULTS: The group A was formed by 94 children, 23 of them was positive
      to Hp antigen (24.46%) and negatives 71 (75.54%). The group B was formed by 94
      children, 17 of them was positive to Hp antigen (18.08%) and negatives 77
      (81.92%). The group C was formed by 94 children, two of them was positive to Hp
      antigen (2.12%) and 92 negatives (97.88%). Statistically significant differences
      was found in: The days that eat meat, the drainage in the domicile, in the
      prevalence of antigen, if they have breakfast every day, the number of persons
      who live in the room, if there is drinkable water in the domicile, if they have
      drainage in the domicile, if they present diarrheic stools, if they possess wild
      animals. And no relation with the age, the kind (genre), the existence of
      domestic animals and the presence of abdominal pain. CONCLUSIONS: It is a
      question of three different populations in the same territory, the first one
      located in a conurban zone of regular services of health demonstrates a
      prevalence of almost 25%. The second from a rural zone, who live and study out of
      the circle of the city and in this one found 18% of positive results and the
      third group living in the city but with all the sanitary services that reported
      2%. Only the drainage presence intra domiciliary and the fact that they were
      eating meat a week demonstrated to have statistic importance in three groups. To
      have drinkable water and the number of persons who coexist in the house
      demonstrated the sanitary conditions that also prevailed statistically in the
      group A and B in relation to the control group; The presence of diarrheic stools
      in the group A statistically significant make us suspect that one hand the
      sanitary environmental conditions to that these children are submitted are not
      the bestones.

PMID- 17542277
TI  - [Frequency of NAFLD in a group of patients with metabolic syndrome in Veracruz,
      Mexico].
AB  - INTRODUCTION: Nonalcoholic fatty liver disease is a very common disease that is
      being described principally in obese, diabetic and hiperlipidemic patients
      without significant alcohol consumption (less than 28 ethanol Units per week).
      Nowadays it is considered as the hepatic manifestation of the metabolic syndrome.
      The frequency of Non Alcoholic Sreatohepatic (NASH) is 30 to 35% in general
      population, but it reaches to 70% in patients whose Body Mass Index (BMI) is
      above 30 kg/m2 as it occurs with diabetic patients. In Mexico there are only
      isolated reports about it's frequency, nearly 7.1% in general population and
      18.5% in diabetic patients. OBJECTIVE: To know the frequency of the Nonalcoholic
      fatty liver disease in patients who receive medical attention at the city of
      Veracruz. MATERIAL AND METHODS: We studied 337 patients, who were divided into 4
      groups: Normal Weight, Overweight, Obese and Diabetes type 2 patients. The
      individuals who reported previous hepatitis and alcohol consumption were
      excluded. All patients made a test in order to determinate: age, gender, presence
      of hepatic stigmata and complaints. Laboratory tests were done to all patients
      including: Blood glucose, seric lipids, transaminases, proteins and alkaline
      phosphatase. In those cases with impairment in transaminases results, it was done
      upper abdominal ultrasound (USG) and hepatic biopsy, in patients who accepted.
      RESULTS: We identified 53 cases (15.72%) with characteristics of Nonalcoholic
      fatty liver disease. The frequency in patient with normal weight and overweight
      was 7.14% to 7.76%, while in obese subjects it was 14.15% and 28% in diabetic
      patients; 73.58% of all patients were female and the other 28.41% were males. The
      average age of the group was 48.11 years, it was similar the specific age of the
      normal weight and obese patients, in overweight patients was 61.5 years and the
      average age in diabetics was 56.42 years. There were significant differences in
      the results of blood glucose level, glycosilated hemoglobin, cholesterol, seric
      lipid values and aminotransferases in obese and diabetic patients compared with
      normal subjects and overweight patients in our study, the USG did not show
      sensibility and specificity to detect Non alcoholic fatty liver disease (NAFLD).
      DISCUSSION: The results of this study show a lower frequency compared with the
      rest of the world, however it was higher in diabetic population than the
      frequency published by Bernal in Hidalgo, Mexico. The aminotransferases level
      resulted elevated in all patients with metabolic syndrome and NAFLD so we
      consider that elevated aminotransferases levels is the best predictor to suspect
      the presence of NAFLD. That is why it's very important to consider the
      possibility to avoid the progression to cirrhosis and hepatocarcinoma.

PMID- 17542278
TI  - [Prevalence of NAFLD and metabolic syndrome in asymtomatics subjects].
AB  - Non Alcoholic Fatty Liver Disease (NAFLD) is a frequent entity to progress to
      liver fibrosis and cirrhosis, and it is associated with several metabolic
      disturbances. The insulin resistance is often considered the link between
      metabolic disturbances and NAFLD. The aim of this study was to determine the
      prevalence of NAFLD in healthy population and the prevalence of metabolic
      syndrome in this patients. The associated factors to develop liver cirrhosis were
      identified. METHODS: 2,503 records were reviewed and the presence of steatosis
      was determined by ultrasonography. A clinical and biochemical examination was
      carried out and the metabolic criteria were defined according to the ATP III.
      RESULTS: 427 (17.05%) patients with NAFLD were detected. 359 (14.3%) with NAFLD
      were included, the mean age was 46.26 +/- 9.85 years. Overweight was present in
      46.79% and obesity in 36.49% of patients. The association between DM, HAS, high
      levels of cholesterol and triglicerides was found in 3.6, 13.6, 63 and 43%,
      respectively. Steatohepatitis was found in in 34% of patients high levels of AST.
      AST/ALT ratio > 1 was detected in 76 patients (21.16%). According to the ATP III
      criteria, the prevalence of metabolic syndrome in patients with NAFLD was 22.8%.
      CONCLUSIONS: The frequency of NAFLD and metabolic syndrome in this study was
      14.3% and 22.8%, respectively. Overweight, obesity and dyslipidemia were the main
      associated factors to NAFLD.

PMID- 17542279
TI  - [Gastrointestinal cancer in four medical centers in Mexico City. A 25-year
      study].
AB  - BACKGROUND: Digestive cancer is an important mortality cause in Mexico. In the
      past decades a change in the frequency of digestive malignancies has been
      observed. AIM: To evaluate the frequency of digestive malignancies in four
      hospitals in Mexico City during a 25 years period. PATIENTS AND METHODS: All
      digestive cancers were studied at the following hospitals: Hospital General de
      Mexico (HGM), Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubirdn
      (INCMNSZ), Centro Medico Nacional 20 de Noviembre (CMN20Nov) and Hospital Espanol
      (HE). The diagnosis was established by histopathology study. Cases frequency is
      were compared in three-years intervals. RESULTS: 8,879 digestive cancers were
      documented. Gastric cancer frequency decreased during the study period at HGM
      (59% in 1978 to 38% in 2003) and at INCMNSZ (32% in 1978 to 24% in 2003), p =
      0.013 andp = 0.012 respectively. Colon cancer frequency increased significantly
      at HGM (15% in 1978 to 36% in 2003, p < 0.001) and at CMN20Nov (20% in 1981 to
      51% in 2003, p < 0.01) and at INCMNSZ with tower significancy. A change in
      squamous esophageal cancer (SC) and esophageal adenocarcinoma (EA) frequencies
      was observed in at the INCMNSZ, with a SC:EA ratio of 7:1 between 1977 to 1987and
      1:2 between 1988 to 2005. Alimentary habits questionnaries showed early during
      the study diferences in caloric intake between the four hospitals (mean HGM:
      2,169 kcal, INCMNSZ: 2,195 kcal, CMN2O0Nov: 3,133 y 2,262 kcal HE) and in animal
      protein intake, being lower at HGM (9.3 g/day) and IN-CMNSZ (11.8 g/day) compared
      with CMN2ONov (45.6 g/day) and HE (63.4 g/day), in the next questionnary these
      differences dissapeared and there was an increase in both, the same was observed
      for lipid intake. CONCLUSIONS: We observed a reduction in gastric cancer fre
      quency and an increase in colon cancer in 25 years, probably associated to a
      change in habits dietary. Also a change in the main histological type of
      esophageal cancer was observed, initially epidermoid cancer was the most frequent
      and in the last 10 years adenocarcinoma is the most frequent.

PMID- 17542280
TI  - [Prevalence of periampullary diverticular, its association with
      choledocolithiasis and technical sucess with ERCP].
AB  - BACKGROUND: Periampullary diverticula (DP) are thought to be associated with bile
      duct stones; they may influence the index of success or failure at endoscopic
      retrograde cholangiopancreatography (CPE) and may increase the risk of its
      complications. AIM: Assess the association between DP with bile duct stones and
      its contribution with the technical success at CPE. METHODS: Two hundred and
      forty five consecutive patients who were undergoing CPE between April 1st and
      September 23th were prospectively entered into a database. Patients with and
      without DP were identified and compared. DP prevalence, its association with bile
      duct stones and with the technical success at CPE, and immediate complications
      were determined. Chi squared, Student t and Fisher exact test were used. RESULTS:
      A total of 205 cases were included. DP prevalence was 10. 7% (IC 95% 8.6-12.8)
      Mean age of patients with DP (68 vs. 52 years) (p = 0.001) and the incidence of
      choledocholithiasis (81% vs. 49%) (p = 0.004) were greater in DP group. There
      were no significant differences found between DP group and the control group in
      terms of successful duct cannulation (90% vs. 89%), satisfactory sphincterotomies
      (95% vs. 93%) or stone extraction (77% vs. 75%). There was an increased frequency
      of hemorrhage in the DP group (9% vs. 4%) however the difference was no
      significant. CONCLUSIONS: DP is associated with an increased incidence of
      choledocholithiasis. DP did not cause any major technical difficulties at CPE.

PMID- 17542281
TI  - [Radical surgical treatment of a new neuroendocrine tumor of the ileocecal valve
      with liver metastasis and carcinoid syndrome].
AB  - BACKGROUND: Neuroendocrine tumors are rare neoplasms which have a slow growth
      pattern. When liver metastases are diagnosed, treatment is controversial and it
      is focused in symptomatic control. AIM: To present a patient with a
      neuroendocrine tumor that arised from the ileocecal valve and it was diagnosed
      with carcinoid syndrome and treated with radical liver and colonic resection. A
      discussion of the different forms of treatment is presented. CASE REPORT: A 41
      year-old woman was sent to our hospital with liver metastases and carcinoid
      syndrome from a neuroendocrine tumor of the ileocecal valve for treatment. Right
      colectomy, right hepatic trisectionectomy and radiofrequency ablation of two left
      sided lesions was performed as a first procedure. A second procedure was
      performed two months afterwards when resection of residual left sided lesions was
      done. After a two year follow up a 2 cm residual liver lesion was diagnosed and
      percutaneous radiofre-quency ablation was done. After four years of follow up the
      patient has been asymptomatic without tumor recurrence CONCLUSIONS: Radical
      surgical treatment of neu-roendocrine tumors controls symptomatology, improving
      quality of life and survival. However, this treatment should only be performed in
      a well selected group of patients.

PMID- 17542282
TI  - [Combined hepato-cholangiocarcinoma. Case presentation and literature review].
AB  - More than 80% of primary liver cancers are hepatocellular carcinoma. The second
      most frequent primary tumors of the liver are cholangiocarcinomas, accounting for
      about 15% of primary liver cancers. Less frequent tumor types is the combined
      hepatocellular-cholangiocarcinoma (CHC), a rare primary liver tumor showing both
      hepatocellular and bile duct differentiation, and mostly represent less than 5%
      of primary liver cancer The histogenesis of CHC has been unclear Differentiation
      potential of hepatocyte and biliar epithelium is closely related to the common
      embryonic origin and various states of cellular differentiation. Some
      investigators suggested that CHC originated from intermediate type cells or
      progenitor cells with dual potential. A rare case of CHC in a 58-year-old female
      patient is presented. A critical review of the literature discussing
      clinicopathologic features is also presented.

PMID- 17542283
TI  - [Therapeuric aspects of NAFLD. A literature review].
AB  - The prevalence of non-alcoholic steatohepatitis has increased in the last years,
      paralleling the increasing incidence of overweight and obesity in the general
      population and related comorbidities. It is expected that in near future, non
      alcoholic steatohepatitis will be responsible for a large number of subjects with
      chronic liver disease due to fatty liver Because of this, treatment options for
      fatty liver are necessary. To date, the cornerstone of treatment is based in
      weight reduction, with diet and increased physical activity, although reports
      indicating that insulin sensitizers and medications that reduce oxidative stress
      may hold promise for the treatment of this condition. This article reviews the
      most important aspects of treatment of non-alcoholic steatohepatitis.

PMID- 17542284
TI  - [Current concepts in the pathophysiology, diagnosis and treatment of fecal
      incontinence].
AB  - Fecal incontinence (FI), defined as the recurrent uncontrolled passage of fecal
      material due to the inability to control bowel discharge is a common and
      devastating condition. According to previous studies, at least 1 in 10 adult
      women have FI. This disorder poses a significant economic burden and has a
      negative impact on patient's lifestyle, leads to a loss of self-confidence,
      social isolation and a diminished quality of life. Three subgroups of FI are
      recognized: a) passive incontinence: the involuntary discharge of stool or gas
      without awareness; b) urge incontinence: the discharge of fecal matter in spite
      of active attempts to retain bowel contents, and c) fecal seepage: the
      involuntary leakage of small volumes of stool after normal evacuation. Disruption
      of the normal structure or function of the anorectal unit leads to FI and is
      often due to multiple mechanisms. A detailed history and examination including
      digital rectal examination facilitates diagnosis. Anorectal physiological tests
      provide useful information regarding functional abnormalities and anal
      endosonography regarding sphincter defects. These tests provide insights
      regarding pathophysiology and can guide further management. Behavioral therapy is
      successful in most patients and should be offered first. Surgical treatment
      should be considered in cases who fail medical treatment or with sphincter
      defects. Several experimental approaches, including bulking of the anal
      sphincter, sacral nerve stimulation and the delivery of radiofrequency energy to
      the anal canal are under investigation.

PMID- 17542285
TI  - [Clinical images in gastroenterology. Radiofrequency ablation of the right lobe
      hepatocarcinoma].

PMID- 17542286
TI  - [Clinical images in gastroenterology. GIST of the stomach].

PMID- 17542287
TI  - [NAFLD and metabolic syndrome a troublesome association].

PMID- 17542288
TI  - [American Gastroenterological Association Institute medical position statement on
      the use of endoscopic therapy for gastroesophageal reflux disease].

PMID- 17542289
TI  - Colorectal cancer in India: present status.

PMID- 17542290
TI  - Nonalcoholic fatty liver disease in India--is it different?
AB  - Nonalcoholic fatty liver disease (NAFLD) is an emerging clinical entity. There is
      limited data on NAFLD from India. The objective of this article was to review all
      the published literature on NAFLD from India. The epidemiological studies
      including prevalence ofNAFLD amongst special groups like in those with
      unexplained rise in transaminases, diabetes mellitus and cryptogenic cirrhosis,
      studies on pathogenesis including insulin resistance, iron abnormalities, and
      studies available for the treatment of such patients have been reviewed. In
      addition some of the differences between Indian patients and those from the West
      have been highlighted. Available literature show that majority of Indian patients
      with NAFLD have overweight or obesity as per Asian Pacific criteria even though
      they do not have the kind of morbid obesity as seen in patients from the West.
      Other differences between Indian patients and those from the West include less of
      metabolic syndrome including its components like diabetes mellitus and
      hypertension, less of iron abnormalities and HFE gene mutations and mild
      histological disease at presentation in Indian patients. More data is required to
      substantiate these findings and to prove if NAFLD patients in India are different
      at presentation.

PMID- 17542291
TI  - Gastrointestinal problems at high altitude.
AB  - Gastrointestinal (GI) problems at high altitude are commonplace. The
      manifestations differ considerably in short-term visitors, long-term residents
      and native highlanders. Ethnic food habits and social norms also play a role in
      causing GI dysfuntion. Symptoms like nausea and vomiting are common
      manifestations of acute mountain sickness and are seen in 81.4% short-term
      visitors like mountaineers. Anorexia is almost universal and has a mutifactorial
      causation including effect of hormones like leptin and cholecystokinin and also
      due to hypoxia itself. Dyspepsia and flatulence are other common symptoms.
      Diarrhoea, often related to poor hygiene and sanitation is also frequently seen
      especially among the short-term visitors. Peptic ulceration and upper gastro
      intestinal haemorrhage are reported to be common in native highlanders in the'
      Peruvian Andes (9.6/10000 population per year) and also from Ladakh in India. A
      hig h incidence o f gastriccarcinoma is also reported, especially from Bolivia
      (138.2 cases per 10000 population per year). Megacolon and sigmoid volvulus are
      common lower GI disorders at high altitude. The latter accounted for 79% of all
      intestinal obstructions at a Bolivian hospital. Thrombosis of the portosystemic
      vascultature and splenic hematomas has been reported from India. Malnutrition is
      multifactorial and mainly due to hypoxia. Fat malabsorption is probably
      significant only at altitudes > 5000m. Neonatal hyperbilirubinemia was found to
      be four times more common in babies born at high altitude in Colorado than at sea
      level. Gall stones disease is common in Peruvian highlands. A high seroprevalence
      of antibodies to H pylori (95%) has been found in Ladakh but its correlation to
      the prevalence of upper gastro-intestinal disease has not been proven.

PMID- 17542292
TI  - A review of evidence based management of colorectal cancers.

PMID- 17542293
TI  - Diagnostic value of serum CA242, CA 19-9, CA 15-3 and CA 125 in patients with
      carcinoma of the gallbladder.
AB  - BACKGROUND: Tumor markers have an increasing significance in the diagnosis and
      evaluation of tumor, but their role in gallbladder cancer has not been
      established. The present study was undertaken to determine the utility of
      serological markers in carcinoma of the gallbladder (CaGB). METHODS: This study
      was carried out in 55 cases and 8 healthy controls presenting to a single
      surgical unit of the University Hospital, Varanasi, India. CA242, CA19-9, CA15-3
      and CA125 were assayed preoperatively in serum of patients with carcinoma of the
      gallbladder (39), cholelithiasis (16) and healthy controls (8) using ELISA
      technique. RESULTS: Mean concentration of all tumor markers was significantly
      raised in carcinoma of the gallbladder when compared with cholelithiasis. CA 242
      was 12.10 vs 42.19 u/ ml, CA19-9 was 211.27 vs 86.06 uml, CA 15-3 was 71.42 vs
      1.93u/ml and CA125 was 253.61 vs 65.5 u/ml <0.05). Sensitivity and specificity
      were calculated at various cut off points. Significant changes in CAl9-9 and
      CA242 occurred with advanced stage (p <0.05) and grade of tumor (p<0.00 1). When
      two tumor markers were combined, like CA242 and CA125, sensitivity and
      specificity improved to 87.5% and 85.7% respectively. Diagnostic accuracy is
      highest with a combination of CA 19-9 and CA 125 (80.65%). However, combination
      of tumor markers did not improve any further sensitivity or specificity of
      markers. CONCLUSION: Assay of CA242, CA15-3, CA19-9 and CA 125 are fairly good
      markers for discriminating patients of carcinoma of the gallbladder from
      cholelithiasis. CA242 and CA125 when used together achieved best sensitivity and
      specificity. Serum markers seem to be less sensitive when used individually in
      carcinoma of the gallbladder but may prove useful in combination.

PMID- 17542294
TI  - Is Helicobacter pylori eradication indicated in cirrhotic patients with peptic
      ulcer disease?
AB  - INTRODUCTION: The association between H. pylori infection and peptic ulcer
      disease (PUD) and the efficacy of eradication of H. pylori in treating ulcer
      disease in cirrhotic patients remains controversial. This study was carried out
      to ascertain the prevalence and significance of H. pylori in cirrhotic patients
      with PUD and to assess the need for anti H. pylori thrapy METHODS: Three groups
      of patients were studied . These were patients with (A) cirrhosis and PUD, (B)
      uncomplicated PUD and (C) cirrhosis without PUD. H. pylori status was determined
      by endoscopic urease test . Eradication therapy was given with a four drug
      regimen and repeat endoscopy was done three months later to detect ulcer healing
      as well as H. pylori status with PUD in groups A and B. RESULTS: Cirrhotic
      patients with PUD had a significantly lesser prevalence of H. pylori compared to
      uncomplicated ulcer patients (46.9 % vs 80 %; p = 0.04). While H. pylori
      eradication rates were similar between cirrhotic and non cirrhotic patients,
      ulcer healing rate was significantly lesser in cirrhotic patients ( 48 % vs 80.9
      %) . Majority of residual ulcers in cirrhotic patients were negative for H.
      pylori. CONCLUSION: Eradication of H. pylori does not reduce the residual ulcer
      rate indicating that H. pylori infection might not be a significant risk factor
      for PUD in cirrhotic patients. Hence, routine H. pylori eradication might not be
      warranted in patients with cirrhosis and peptic ulcer disease.

PMID- 17542295
TI  - Laparoscopic common bile duct exploration for extraction of a round worm.
AB  - A 35 years old lady presented with fever, biliary colic, mild jaundice,
      indigestion and flatulence. The upper abdominal ultrasonography revealed
      cholecystitis with sludge and a round worm in the common bile duct. Laparoscopic
      cholecystectomy and exploration of the bile duct for the removal of round worm
      was performed. The post-operative period was uneventful and the patient was
      discharged fit on the 4th post-operative day.

PMID- 17542296
TI  - Endoscopic examination of the upper esophagus by withdrawal of endoscope over
      guide wire.
AB  - Upper gastrointestinal (UGI) endoscopy is an important diagnostic modality in
      evaluation of patients with upper gastrointestinal (GI) disorders. However,
      lesions located in the cricopharyngeal area and upper esophagus can be missed, as
      this area may not be well visualized during endoscopy. This study was conducted
      to study the utility of a new technique of endoscopic examination of the upper
      esophagus by withdrawal of endoscope over guide wire in diagnosing esophageal
      disorders. Patients with suspected upper esophageal disorders on history and
      radiological investigations were assessed using guide wire assisted endoscopic
      examination during withdrawal of the endoscope. In this technique, endoscope is
      inserted into the esophagus under vision and thereafter the whole of esophagus,
      stomach and proximal duodenum is examined. The endoscope is then withdrawn into
      the mid-esophagus, a guide wire is fed into the biopsy channel, and thereafter
      inserted into the esophagus. Once guide wire has been advanced into the
      esophagus, the endoscope is withdrawn gently over the guide wire into esophagus
      carefully examining for lesions in upper esophagus and cricopharyngeal area.
      Twenty cases of various abnormalities localized to the upper esophagus were
      studied. The final diagnosis in these patients was cervical esophageal web (10),
      post transhiatal esophagectomy leak (4), heterotopic gastric mucosa (3),
      posttraumatic esophageal perforation (2), and Zenker's diverticulum (1). Intact
      web was detected in 2 patients and in 8 patients fractured web was seen. Guide
      wire assisted examination of upper esophagus improved the ability to visualize
      and characterize these lesions and no complications were encountered as a result
      of this procedure. Endoscopic examination of the upper esophagus by withdrawal of
      endoscope over guide wire is safe and effective in diagnosing anatomical
      abnormalities of the upper esophagus that may be missed or poorly characterized
      during standard endoscopy.

PMID- 17542297
TI  - Pancreatic metastasis from renal cell carcinoma 16 years after nephrectomy: a
      case report and review of the literature.
AB  - Two percent of all malignant pancreatic tumors are metastases from other
      primaries, with small cell lung cancer, colorectal cancer, breast cancer and
      hematological neoplasms being the commonest. Renal cell carcinoma (RCC)
      metastasizing to the pancreas is rare and occurs in 2.8% of patients with
      metastatic RCC. However, RCC is the most common primary leading to solitary
      pancreatic metastasis. Metastases often present many years after nephrectomy for
      primary RCC (median time of 8 years) and should therefore be looked for on
      surveillance or when patients present with upper abdominal symptoms. Complete
      surgical resection when possible offers the best chance for cure.

PMID- 17542298
TI  - Mesenteric fibromatosis with involvement of the gastrointestinal tract.
AB  - Primary mesenteric fibromatosis is a rare condition. The aggressive nature of
      these tumors and the potential for major morbidity secondary to resection makes
      it a challenging disease for the surgeon. We report a case of mesenteric
      fibromatosis with involvement of small bowel.

PMID- 17542299
TI  - A case of failed colonoscopy due to inguinal hernia.

PMID- 17542300
TI  - IRS approves IT subsidies. Ruling means hospitals can underwrite doc EHRs.

PMID- 17542301
TI  - Ascending in healthcare. Roman Catholic Ascension Health has made a Fortune 500
      name for itself with business acumen, risk-taking and efficiency.
AB  - In less than a decade, Ascension Health has risen to the top tier of U.S.
      healthcare systems, with operating revenue that bests household names like Google
      and Amazon.com. Helping lead the system's meteoric rise is CEO Anthony Tersigni,
      left. "We are a ministry. We're not a business. We do business practices for one
      basic reason: We have bondholders who are counting on us to repay the bonds."

PMID- 17542302
TI  - Building on 'four cornerstones'. Leavitt panel enlists insurers to promote
      transparency.

PMID- 17542303
TI  - Uninsured billing study deja vu? Critics argue that data are old, changes have
      been made.

PMID- 17542304
TI  - Disciplinary actions drop, but...delayed Public Citizen report may not be so
      rosy.

PMID- 17542305
TI  - HIGPA, ex-CEO settle. Betz gets undisclosed sumin case over travel fees.

PMID- 17542306
TI  - IRS to dig into bond records. Agency to survey select charities on record
      retention.

PMID- 17542307
TI  - Perspective on pricing. Study puts hard numbers on a billing issue that may not
      have gone away.

PMID- 17542308
TI  - Small numbers are a big deal. Rural providers need to report on quality, but
      sparse data demand new solutions.

PMID- 17542309
TI  - On critical list, but doing fine. Critical-access hospitals run by for-profit
      operators--though few in number--show one path to fiscal health for rural
      facilities.

PMID- 17542310
TI  - In the interest of privacy. Deborah Peel has some blunt words on the increased
      push for data-mining.

PMID- 17542311
TI  - State loses data-mining case. N.H. plans appeal of ruling allowing use of Rx
      data.

PMID- 17542312
TI  - Infant feeds.

PMID- 17542313
TI  - Now and then: nursing's unwanted child.

PMID- 17542314
TI  - Children's participation in research.

PMID- 17542315
TI  - Mouth care in children with cancer.

PMID- 17542316
TI  - Malnutrition in low income countries: lessons from the field.

PMID- 17542317
TI  - Exploring the assessment process.
AB  - Assessment is a fundamental nursing skill that underpins decisions about
      interventions and priorities in care delivery. Rather than the holistic,
      individualised approach envisaged in the nursing process, nursing assessment of
      the sick child in hospital appears to focus mainly on quantitative data and
      preventing clinical failures. In this article, Carper's (1978) four 'patterns of
      knowing in nursing' are used to illustrate how assessment could be broadened to
      better inform nurses' decision making and to make child and family-centred care
      more of a reality.

PMID- 17542318
TI  - Discharge management for children with complex needs.
AB  - There is now an expectation that children with complex (often technology
      dependent) care needs will be cared for at home by parents who assume 24-hour
      responsibility following extensive training to nurse, care for and parent their
      child. A variety of models of discharge planning exist but the planning and
      process of discharge are persistently reported to be problematic from the
      perspective of families, professionals and commissioners. A consultation exercise
      with both parents and professionals indicated that nurses, doctors and social
      workers would benefit from some practical help and specific knowledge relating to
      complex discharge management. This article summarises best practice and, where
      possible, evidence-based principles and procedures with the intention of
      contributing to the establishment of effective models of discharge management and
      ongoing homecare, and improved outcomes for children and families. Guidance on
      putting together and costing a care package proposal, and applying risk
      management and clinical governance procedures in home-based settings will be
      published in the June issue of Paediatric Nursing.

PMID- 17542319
TI  - Mentorship: the art and science.

PMID- 17542320
TI  - Pilot student placements with children with complex needs.
AB  - Enabling the increasing population of children with complex and continuing health
      needs to live at home with their families is generally considered the ideal
      approach. Services for children with complex needs are commissioned from a wide
      range of providers, including the private and voluntary sectors. Pilot placements
      for two student nurses with a private company that had a significant caseload of
      children with complex and continuing needs were evaluated as a way of enabling
      student nurses to develop knowledge and skills in this field. The objective was
      to increase understanding of the issues involved in facilitating this type of
      placement and to develop placements in line with the findings. Semi structured
      interviews with students and mentors were used to generate evaluative data. The
      placement was well evaluated by all parties. Students gained important clinical
      skills but also appreciated in greater depth the humanistic needs of children,
      young people and their families. Advantages of working with a company whose focus
      is the provision of complex care at home included variety and continuity in the
      placement and a greater number of families across whom the students can be spread
      to avoid excessive or constant intrusion. Such placements can offer valuable
      learning opportunities, however, ongoing development and evaluation of placements
      is needed, particularly as these are predominantly based in family homes.

PMID- 17542321
TI  - Cross-boundary rotational working for neonatal nurses.
AB  - Neonatal services in England and Wales are undergoing significant changes as a
      result of technological advances as well as the development of new networks.
      These changes have had a dramatic effect on the neonatal workforce. The skills of
      the available staff govern the level of activity of neonatal units: many units
      have had to re-evaluate the services they can safely deliver with the available
      workforce. This has resulted in the re-configuration of some neonatal units and
      changes in the dependency levels of many. Units have had to undertake reviews of
      the patterns of working of their staff to ensure that a skilled and competent
      workforce is available to provide the level of care each neonatal service
      requires. Shortages in some areas have meant that units have had to find new ways
      to retain and update skilled staff. This article describes a rotational programme
      developed with the aim of providing a continued clinical development pathway for
      neonatal nursing staff. The programme incorporates competency assessments of
      emergency skills and clinical and technological advances in neonatal care.

PMID- 17542322
TI  - A care bundle for management of central venous catheters.
AB  - Central venous catheters (CVCs) are an essential tool in paediatric intensive
      care, providing a means to monitor patient haemodynamics and to administer
      fluids, nutrition, blood products and medications. Because multiple factors
      contribute to the high risk of catheter related infection, a multi-strategy
      approach is required to prevent such infections. Using contemporary literature
      and clinical audit findings a 'care bundle' was created for use within the PICU
      at Birmingham Children's Hospital. This care bundle groups together best
      practices in order to prevent catheter related bloodstream infection.

PMID- 17542323
TI  - Fireworks spark explosive debate at RCN congress 2007.

PMID- 17542324
TI  - Getting back in rhythm.

PMID- 17542325
TI  - Care pathways for domestic violence.

PMID- 17542326
TI  - Remote control.

PMID- 17542327
TI  - A bid for freedom.

PMID- 17542328
TI  - A new solution to pain control.

PMID- 17542329
TI  - Penile fracture.

PMID- 17542330
TI  - Resuscitation of patients during pregnancy.
AB  - Although the risk of cardiac arrest during pregnancy is rare, the outcome for
      both mother and baby depends on effective resuscitation measures. Maternal
      resuscitations differ from other adult resuscitation attempts, and it is vital
      that emergency nurses can identify these variations in practice and apply them
      appropriately.

PMID- 17542331
TI  - Anaphylaxis: recognition, treatment and education.

PMID- 17542332
TI  - Managing acute heroin overdose.

PMID- 17542333
TI  - Board's eye view.

PMID- 17542334
TI  - Molecular interactions between bacteria, the epithelium, and the mucosal immune
      system in the intestinal tract: implications for chronic inflammation.
AB  - In the last few years, advances in immunology, metabolomics and microbial ecology
      have shown that the contribution of the intestinal microbiota to the overall
      health status of the host has been so far underestimated. In this context,
      intestinal epithelial cells play a crucial role in the maintenance of intestinal
      homoeostasis. Indeed, at the interface between the luminal content and host
      tissues, the intestinal epithelium must integrate pro- and anti-inflammatory
      signals to regulate innate and adaptative immune responses, i.e. to control
      inflammation. However, under the influence of environmental factors, disturbance
      of the dialog between enteric bacteria and epithelial cells contributes to the
      development of chronic inflammation in genetically susceptible hosts. The present
      review covers the state of knowledge of the host response, especially in
      intestinal epithelial cells, to enteric bacteria, including colitogenic and
      probiotic bacteria. It also seeks to give an overview of potential regulatory
      mechanisms involved in the maintenance of intestinal homeostasis, and discusses
      the clinical implications for inflammatory bowel diseases.

PMID- 17542335
TI  - Taxonomy of Lactobacilli and Bifidobacteria.
AB  - Genera Lactobacillus and Bifidobacterium include a large number of species and
      strains exhibiting important properties in an applied context, especially in the
      area of food and probiotics. An updated list of species belonging to those two
      genera, their phylogenetic relationships and other relevant taxonomic information
      are reviewed in this paper. The conventional nature of taxonomy is explained and
      some basic concepts and terms will be presented for readers not familiar with
      this important and fast-evolving area, which importance is often underestimated.
      The analysis of biodiversity and its cataloguing, i.e. taxonomy, constitute the
      basis for applications and scientific communication: reliable identification and
      correct naming of bacterial strains are not only primary aims of taxonomic
      studies, but also fundamental elements in an applied context, for the tracking of
      probiotic strains and a non fraudulent labelling of fermented milks and
      pharmaceutical products containing probiotic microorganisms. A number of
      resources freely available have been listed and their use is suggested for people
      concerned with different aspects of taxonomy. Some perspectives in taxonomy have
      been outlined, in particular considering the role of culture independent analyses
      to reveal the still unknown and uncultured microorganisms. Finally, the impact of
      the availability of whole-genome sequences in taxonomy is briefly explained: they
      have already begun to give insights on bacterial evolution, which will surely
      have implications on taxonomy, even if the analysis of data for lactic acid
      bacteria is still limited to few species.

PMID- 17542336
TI  - Pharmacokinetics and antimicrobial dosing adjustment in critically ill patients
      during continuous renal replacement therapy.
AB  - Appropriate antimicrobial therapy poses one of the greatest challenges during the
      management of a septic patient in the intensive care unit (ICU). Acute renal
      failure (ARF) is a common complication of sepsis and often occurs as a component
      of multiple organ dysfunction syndrome. Continuous renal replacement therapy
      (CRRT) is increasingly used as an effective extracorporeal blood purification
      therapy in this critically ill patient population. Available data demonstrate
      that sepsis, ARF and different modalities of CRRT may have profound effects on
      the pharmacokinetics and pharmacodynamics of various antimicrobial agents used in
      the ICU. Guidelines for antimicrobial prescription which will fit the individual
      patient undergoing a particular method of treatment are still unavailable.
      Understanding the principles of drug removal by CRRT and pharmacokinetics of
      various agents can help to modify the drug dosage and dosing intervals for
      individualized therapy. Meanwhile, monitoring the drug serum concentration is
      still mandatory whenever clinically feasible.

PMID- 17542337
TI  - Single daily dose of cyclosporine in patients with primary glomerulonephritis and
      nephrotic syndrome.
AB  - AIMS: Single daily dose cyclosporine (SDD-CsA) might be a new option providing
      comparable efficacy, increased compliance and less nephrotoxicity compared to
      standard twice-daily dose cyclosporine (TDD-CsA). The aim of this trial was to
      prove the feasibility of SDD-CsA as primary and secondary maintenance therapy in
      patients with nephrotic syndrome. METHODS: We treated 25 adult patients with
      nephrotic syndrome and chronic primary glomerulonephropathy with SDD-CsA for a
      period of 12 months or more. 12 patients were pre-treated with twice-daily dose
      cyclosporine (TDD-CsA) and were then switched secondarily to a single daily dose
      after a median period of 8 months (sSDD-CsA). 13 patients were treated primarily
      with single daily dose cyclosporine (pSDD-CsA). RESULTS: In primary SDD-CsA
      patients, proteinuria decreased significantly from 9.2 - 0.8 g/l (p = 0.02) and
      serum protein increased significantly from 54 - 71 g/l (p = 0.03) during the
      study period. In secondary SDD-CsA patients, serum protein increased further (64 
      69, p = 0.04) after switching to SDD-CsA. In secondary SDD-CsA patients, the
      median total daily CsA dose was significantly lower (200 mg) with SDD-CsA
      compared to previous twice-daily dosing (300 mg, p = 0.01). Serum creatinine did
      not differ significantly before and after therapy and between the groups.
      CONCLUSIONS: SDD-CsA is effective in patients with nephrotic syndrome as primary
      and secondary maintenance therapy. SDD-CsA allows for significantly lower total
      daily doses, probably with less nephrotoxicity.

PMID- 17542338
TI  - Renal pathological change in patients with type 2 diabetes is not always diabetic
      nephropathy: a report of 52 cases.
AB  - AIMS: The present study examined the relationship between clinical features and
      renal histological changes in the Type 2-diabetic patients and evaluated the
      usefulness of renal biopsy in the diagnosis of diabetic versus non-diabetic
      kidney disease. METHODS: 52 patients with Type 2-diabetic mellitus were
      retrospectively analyzed for differential clinical, laboratory features and
      pathological characteristics including overt proteinuria (> 0.5 g/day), elevated
      serum creatinine and/or the development of hematuria. RESULTS: Of 52 patients, 20
      cases (38.5%) showed no detectable diabetic lesions and, thus, were diagnosed as
      non-diabetic renal disease (NDRD), while 32 patients (61.5%) exhibited diabetic
      nephropathy. Interestingly, while 29 patients showed diabetic nephropathy (DN)
      alone, NDRD was also found in 3 patients with DN. Clinically, 24 out of 52
      patients (46.16%) had a diagnosis consistent with the pathological findings,
      while 10 (19.23%) were diagnosed incorrectly. Compared to NDRD patients, patients
      with DN had prolonged diabetic history with or without retinopathy, while 25% of
      patients with NDRD exhibited mesangial proliferative glomerulonephritis.
      CONCLUSIONS: NDRD was a common feature in Type 2-diabetic patients with renal
      involvement. The absence of retinopathy and short periods of diabetic history may
      be useful indicators for diagnosis of NDRD clinically.

PMID- 17542339
TI  - Tonsillectomy in the treatment of pediatric Henoch-Schonlein nephritis.
AB  - The exact pathophysiology of HSN remains to be elucidated. Hence, a therapeutic
      strategy that enables curative treatments for all the various grades of HSN
      patients has yet to be established. We report our experience performing
      tonsillectomy combined with steroid therapy for 16 pediatric proteinuric Henoch
      Schonlein nephritis (HSN) patients. All patients exhibited hematuria and
      proteinuria in their first HSN attack with the mean age of onset 7.7 years (range
      4.75 - 13.9 years). Nine patients were diagnosed with clinically severe HSN
      presenting with massive proteinuria (> 1 g/m(2)/day). Renal biopsy findings
      performed in 6 patients were Grade II (3), Grade III (2) and Grade IV (1)
      according to the International Study of Kidney Diseases in childhood
      classification. Tonsillectomy was performed after 1-4 cycles of
      methylprednisolone pulses during oral prednisolone (0.5 - 1.5 mg/kg/day) therapy.
      In 2 patients, oral cyclophosphamide therapy was added before the tonsillectomy.
      The interval between the onset of HSN and tonsillectomy was 97.4 +/- 24.5 days
      (range 27 424 days). In all patients, proteinuria had disappeared by 6 months
      after the tonsillectomy and the urine findings had normalized. The interval
      between therapy initiation and complete remission was 9.6 +/- 2.0 months (range 2
      - 26 months). Over follow-up periods of 4.9 +/- 0.6 years (range 2.2 - 9.3
      years), no recurrences of Henoch-Schonlein purpura or HSN were observed. There
      was a significant correlation between early tonsillectomy performance and
      decreased time until normalization of the urine findings, indicating that the
      tonsils may have pivotal roles in the initiation and progression of HSN. Their
      elimination might promote the reversal of nephritis. Although this study is
      retrospective, we suggested that tonsillectomy at an early stage of HSN may be
      beneficial by shortening the period of illness and contributing to clinical
      recovery. Randomized controlled trials will be needed to confirm this
      supposition.

PMID- 17542340
TI  - The continuous erythropoietin receptor activator (C.E.R.A.) corrects anemia at
      extended administration intervals in patients with chronic kidney disease not on
      dialysis: results of a phase II study.
AB  - AIM: This study was designed to assess the potential of the continuous
      erythropoietin receptor activator (C.E.R.A.) to correct anemia at extended
      administration intervals in erythropoiesis-stimulating agent-naive patients with
      chronic kidney disease (CKD) not on dialysis and to determine its optimal
      starting dose. METHODS: Patients were assigned to subcutaneous C.E.R.A. at 3
      doses: 0.15, 0.30 and 0.60 microg/kg/wk. During the first 6 weeks, dose
      adjustments for efficacy were not permitted in order to assess dose response.
      Within each of the 3 dose groups, patients were randomized to receive C.E.R.A.
      QW, Q2W or Q3W; the total dose during the first 6 weeks was the same for a
      particular dose group across the frequency subgroups. During the next 12 weeks,
      dose was adjusted according to predefined hemoglobin (Hb) criteria. The primary
      efficacy parameter was change in Hb over 6 weeks, estimated from regression
      analysis between baseline and the point at which the patient received a dose
      change or blood transfusion. It therefore provided an estimate of Hb increase
      based on starting dose. Other endpoints included Hb response rate (proportion of
      patients with a Hb increase > 1.0 g/dl on 2 consecutive occasions). A 1-year
      extension period investigated long term tolerability and efficacy. RESULTS: A
      dose-dependent relationship was noted in the mean change in Hb from baseline over
      6 weeks (p < 0.0001), independent of administration schedule (p = 0.9201). There
      was also a significant relationship between Hb change and median serum C.E.R.A.
      concentration (p < 0.0001). Erythropoietic responses were sustained in all groups
      with mean changes from baseline in Hb > 1.2 g/dl observed at doses > or = 0.30
      microg/kg/wk. Hb response rate increased with increasing dose: 67, 72 and 90%
      with C.E.R.A. 0.15, 0.30 and 0.60 microg/kg/wk, respectively. Generally, the
      median Hb response time was faster with increasing dose (89, 43 and 31 days,
      respectively). Response was unrelated to administration frequency. Stable Hb
      concentrations were maintained throughout the 1-year extension period. C.E.R.A.
      was generally well tolerated, and the most common adverse events were
      hypertension, urinary tract infection and renal failure. CONCLUSIONS: C.E.R.A.
      corrected anemia and maintained sustained and stable control of Hb over 1 year.
      These results suggest that 0.60 microg/kg subcutaneous C.E.R.A. given twice
      monthly is a suitable starting dose for further investigation in Phase III
      studies in patients with CKD not on dialysis.

PMID- 17542341
TI  - Retroperitoneal hematoma compressing a single functioning kidney: an unusual
      cause of obstructive renal failure.
AB  - We report a case of a retroperitoneal hematoma occurring in a patient under
      anticoagulation therapy for deep-venous thrombosis and presenting as an anuric
      acute renal failure. A coexisting polycythemia vera led to misdiagnosis that
      could have been life-threatening. A woman, known for polycythemia vera and a
      single functioning right kidney, was admitted with mild abdominal pain in a
      context of recent deep venous thrombosis under low-molecular weight heparin.
      Clinical examination revealed hepatomegaly associated with polycythemia vera.
      Biochemical evaluation disclosed an acute renal failure, and renal
      ultrasonography showed no dilation of the renal pelvis. Retroperitoneal hematoma
      resulted in shock, progressive anemia and obstructive renal failure, related to
      renal pelvic compression. A right renal indwelling catheter was introduced to
      restore urine flow after one hemodialysis session, and an inferior vena cava
      filter was placed because of anti-coagulation contra-indication. However,
      pulmonary embolism occurred, so that oral anticoagulants were introduced. The
      hematoma resorbed spontaneously, and a year after this episode, the patient is
      still alive and well. Retroperitoneal hematoma is a rare cause of obstructive
      acute renal failure and a life-threatening complication of anti-coagulation
      therapy.

PMID- 17542342
TI  - An unusual cause of acute renal failure in a kidney transplant recipient:
      salmonella enteritidis post-infectious glomerulonephritis.
AB  - BACKGROUND: Salmonella enteritidis-associated acute renal failure has often been
      described and is usually a result of dehydration or of rhabdomyolysis. A few
      cases of acute renal failure with glomerular syndrome, caused by S. enteritidis
      infection, have been reported in the literature, but none have been proven by
      histological findings. METHODS: Herein, we report on a case of S. enteritidis
      related glomerulonephritis that occurred in a 42-year-old male transplant
      recipient. He was admitted with fever, signs of urinary infection, diarrhea, and
      nephritic syndrome, i.e. edema, hypertension, increase in serum creatinine,
      microscopic hematuria, proteinuria. His urine culture tested positive for S.
      enteritidis. RESULTS: Under light microscopy, the graft biopsy showed
      proliferative and exudative endocapillary glomerulonephritis. In addition, there
      was polymorphonuclear infiltration of the interstitium, and extra-capillary
      proliferation in one glomerulus. Immunofluorescence showed granular deposits of
      C3 in the mesangium. Electron microscopy showed electron-dense deposits typical
      of humps. He fully recovered on a double antibiotic therapy that included
      ofloxacin and amikacin. CONCLUSION: Although acute renal failure related to non
      typhoidal Salmonella infections are often related to dehydration or
      rhabdomyolysis, this case report shows that it might also be related to immune
      complex-mediated glomerulonephritis manifesting as nephritic syndrome.

PMID- 17542343
TI  - Dialysis catheter-induced superior vena cava syndrome and downhill esophageal
      varices.
AB  - Superior vena cava stenosis is a well-documented complication of central venous
      dialysis catheters. Rarely, this obstruction can lead to the formation of
      downhill esophageal varices. We present a case of esophageal varices as a
      complication of dialysis catheter-induced superior vena cava stenosis, which
      became symptomatic after the placement of an upper extremity arteriovenous graft
      and resolved with percutaneous angioplasty and stenting of the superior vena cava
      stricture.

PMID- 17542344
TI  - A case of a pregnant woman developing systemic lupus erythematosus during
      pregnancy.

PMID- 17542345
TI  - Chylous ascites and chylothorax due to membranous nephropathy.

PMID- 17542346
TI  - Comparative clinical study of the efficacy and safety of a S-metoprolol ER tablet
      versus a racemate metoprolol ER tablet in patients with chronic stable angina.
AB  - OBJECTIVE: To compare the efficacy and safety of a S-metoprolol extended release
      (ER) tablet (50 mg) versus a racemate metoprolol ER tablet (100 mg) in the
      management of angina. METHODS: An open-label, prospective, comparative study in a
      clinical setting was conducted in Indian patients. Patients (n = 50 in each
      group) with a history of angina pectoris, with or without hypertension, were
      administered study medications in a sequential 1:1 manner once daily for 8 weeks.
      The primary efficacy variable was a mean change from baseline in the number of
      angina attacks. The secondary efficacy variables were: mean change from baseline
      in the proportion of patients with no angina attacks, systolic blood pressure,
      diastolic blood pressure, heart rate, and proportion of blood pressure
      responders. Number of patients reporting adverse effects (AEs) and severity of
      AEs in both of the groups were compared. RESULTS: All patients (n = 100)
      completed the study. In the S-metoprolol group the number of angina attacks (mean
      +/- SEM) at baseline and after 2, 4 and 8 weeks of therapy were 6.3 +/- 0.8, 3 +/
      0.4, 1.8 +/- 0.4 and 0.7 +/- 0.2, respectively. In the metoprolol group these
      values were 5.8 +/-1, 3 +/- 0.7, 1.4 +/- 0.3 and 0.7 +/- 0.2, respectively. The
      reduction in the number of angina attacks from baseline was significant (p <
      0.0001) in both groups with no between-group difference. The response rate in
      angina (percentage of patients completely relieved of angina attacks clinically)
      was greater in the S-metoprolol group (72%) when compared to the metoprolol group
      (62%) (p > 0.05, NS). Both study groups showed significant (p < 0.0001) reduction
      in baseline systolic blood pressure (SBP), diastolic blood pressure (SBP) and
      heart rate (HR) in hypertensive patients and a clinically non-significant (p >
      0.05, NS) change in normotensive patients. Among hypertensive patients, the
      response rate in angina was higher in the S-metoprolol group (74%) when compared
      to the metoprolol group (61%) (p > 0.05, NS). In the S-metoprolol group four
      patients reported AEs: fatigue (n = 4), dry mouth (n = 1), dizziness (n = 1),
      dyspnea (n = 2), and mild rash (n = 1). In the metoprolol group three patients
      reported AEs: fatigue (n = 2), dyspnea (n = 1) and dizziness (n = 1). No
      statistically significant difference was detected between the groups in AE
      frequency/severity. CONCLUSION: In routine clinical practice in the management of
      angina (with or without coexisting hypertension), S-metoprolol administered at
      half the dose of the racemate, shows similar efficacy, safety and a trend towards
      a higher response rate.

PMID- 17542347
TI  - Ketorolac as a pre-emptive analgesic in retinal detachment surgery: a
      prospective, randomized clinical trial.
AB  - OBJECTIVE: Retinal detachment surgery is associated with a high incidence of post
      operative pain, nausea and vomiting. Previous studies demonstrated a beneficial
      role of pre-emptive analgesia using regional anesthetic blocks for this type of
      surgery. The aim of the present study was to evaluate the pre-emptive analgesic
      effect of ketorolac in patients undergoing retinal detachment surgery under
      general anesthesia. METHODS: With the approval of the Institutional Ethics
      Committee and written informed consent, 60 adult patients were randomized
      prospectively, in a double-masked manner, to receive intravenously either
      ketorolac 30 mg or saline placebo 30 min before operation. Pain scores at 2, 6,
      12, 18 and 24 h after surgery, the number of patients requiring post-operative
      analgesia, total consumption of analgesics, the incidence of oculocardiac reflex
      as well as the incidence and severity of post-operative nausea and vomiting were
      recorded. RESULTS: The ketorolac group required post-operative analgesia less
      frequently than the placebo group (p < 0.0001). The ketorolac group had
      significantly lower pain scores at all measurement time points (p < 0.001) and
      lower intra- and post-operative total consumption of analgesics (p < 0.01). The
      incidence and severity of nausea and vomiting were lower in patients given
      ketorolac when compared with placebo-treated patients (p < 0.05). The incidence
      of oculocardiac reflex was not significantly different between groups (p = 0.14).
      CONCLUSIONS: The use of ketorolac for pre-emptive analgesia is effective in
      patients undergoing retinal detachment surgery under general anesthesia.

PMID- 17542348
TI  - Atypical antipsychotic therapy for treatment of schizophrenia in Hong Kong
      Chinese patients--a cost analysis.
AB  - OBJECTIVE: To evaluate the direct medical cost of atypical antipsychotic therapy
      for schizophrenia among Hong Kong Chinese patients and to identify factors
      affecting the cost of treatment. METHODS: In this retrospective database
      analysis, patient data were retrieved from three Hong Kong public hospitals.
      Patients aged 2 18 years who received an initial prescription for olanzapine,
      risperidone, quetiapine or amisulpride between April 1 and September 30, 2003;
      and had an ICD-10-coded diagnosis of schizophrenia were included. Patient data
      were collected for a maximum duration of 1 year before and after treatment
      initiation. Primary outcome measures were the schizophrenia-related direct
      medical costs. Demographic and clinical factors were analyzed by multiple
      regression analysis to identify influential factors for the cost of atypical
      antipsychotic therapy. RESULTS: A total of 325 patient records were reviewed and
      82 patients were included in the analysis. Cost per patient per month for clinic
      visits (US$ 67 +/- 41 versus US$ 78 +/- 41), medications (US$ 8 +/- 12 versus US$
      97 +/- 83), and the total cost per patient per month (US$ 314 +/- 898 versus US$
      431 +/- 914) increased significantly after treatment initiation (US$ 1 = HK$
      7.8). Previous duration of hospitalization (RR = 1.00, 95% CI = 1.00 1.01),
      history of substance abuse (RR = 1.26, 95% CI = 1.05 1.52) and use of depot
      antipsychotics (RR = 1.22, 95% CI = 1.05 - 1.42) were associated with higher cost
      of atypical antipsychotic therapy. CONCLUSION: The total direct medical cost
      increased significantly after initiation of atypical antipsychotic therapy in a
      cohort of Chinese patients with schizophrenia. History of drug abuse, use of
      depot antipsychotics and prior duration of hospitalization were positive
      predictors of cost of therapy.

PMID- 17542349
TI  - Pharmacokinetics of sarizotan after oral administration of single and repeat
      doses in healthy subjects.
AB  - OBJECTIVE: Sarizotan is a 5-HTIA receptor agonist with high affinity for D3 and
      D4 receptors. Here we report the pharmacokinetic and tolerability results from
      four Phase 1 studies. MATERIALS: Two single-dose (5 -25 mg, n = 25, 0.5 - 5 mg, n
      = 16) and two multiple-dose (10 and 20 mg b.i.d., n = 30, 5 mg b.i.d., n = 12)
      studies with orally administered sarizotan HCl were carried out in healthy
      subjects. METHODS: Plasma sarizotan HCl concentrations were measured using a
      validated HPLC method and fluorescence or MS/MS detection. Pharmacokinetic
      parameters were obtained using standard non-compartmental methods. RESULTS:
      Sarizotan was rapidly absorbed, group-median times to reach maximum concentration
      (tmax) ranged from 0.5 -2.25 h after single doses and during steady state.
      Maximum plasma concentration (Cmax) and tmax were slightly dependent on
      formulation and food intake, whereas area under the curve (AUC) was unaffected by
      these factors. AUC and Cmax increased dose-proportionally over the tested dose
      range. Independently of dose and time, sarizotan HCl plasma concentrations
      declined polyexponentially with a terminal elimination half-life (t1/2) of 5 - 7
      h. Accumulation factors corresponded to t1/2 values, and steady state was reached
      within 24 h. Plasma metabolite concentrations were considerably lower than those
      of the parent drug. The ratio metabolite AUC : parent drug AUC was time- and dose
      independent for all three metabolites suggesting that the metabolism of sarizotan
      is non-saturable in the tested dose range. CONCLUSIONS: The pharmacokinetics of
      sarizotan were dose-proportional and time-independent for the dose range 0.5 -25
      mg). The drug was well-tolerated by healthy subjects up to a single dose of 20
      mg.

PMID- 17542350
TI  - Under-utilization of gastroprotective drugs in patients with NSAID-related
      ulcers.
AB  - OBJECTIVE: To determine the proportion of patients with a risk of NSAID
      gastropathy receiving adequate gastroprotection. METHODS: This observational
      study was performed between November 2001 and December 2003. We selected patients
      who were hospitalized with perforated and bleeding gastroduodenal ulcers
      attributable to NSAID use and controls without ulcers. Data were collected on
      their sociodemographic characteristics, actual and recent medication, comorbidity
      and medical history. For each patient and control the number of different risk
      factors associated with NSAID gastropathy was calculated. A composite risk factor
      (CRF) was obtained from the sum of all separate risk factors. RESULTS: During the
      observational period a total of 388 patients using NSAID were included in the
      study, 104 patient cases and 284 matched community-based controls. The mean CRF
      was significantly higher in patient cases than in controls (cases mean CRF 3.31
      (SD 1.67) and controls mean CRF 2.76 (SD 1.45), p = 0.002). A total of 148 (38%)
      patients used an adequate preventive strategy. Significant variables for using a
      preventive strategy were concomitant use of steroids (corrected odds ratio 4.22,
      95% CI 2.11 8.47, p < 0.001), a history of gastroduodenal ulcers (corrected odds
      ratio 2.90, 95% CI 1.51 - 5.56, p = 0.001) and concomitant use of low-dose
      aspirin (corrected odds ratio 1.96,95% CI 1.18 3.25, p= 0.01). Among patients
      with 4 or more risk factors associated with NSAID gastropathy, 47% still did not
      use adequate gastroprotection. CONCLUSION: Gastroprotective drugs are greatly
      under-utilized in patients with a risk of NSAID gastropathy.

PMID- 17542351
TI  - Fatal hyponatremia and other metabolic disturbances associated with psychotropic
      drug polypharmacy.
AB  - OBJECTIVE: To report a case of fatal hyponatremia, marked hyperglycemia, and
      acute pancreatitis following simultaneous administration of paroxetine,
      fluphenazine, haloperidol and olanzapine. CASE SUMMARY: A 44-year-old non
      diabetic male was admitted unconsciously, with severe hyponatremia, hyperglycemia
      and bradypnea. The patient had a history of long-term treatment with paroxetine,
      fluphenazine, haloperidol and olanzapine. Upon arrival, the plasma sodium level
      was 104 mmol/l, and blood glucose was 940 mg/dl. The therapy consisted of
      ventilatory support and intensive correction of hyponatremia and hyperglycemia. 2
      hours later, hypotension and refractory cardiac arrest occurred. The autopsy
      disclosed severe cerebral edema as cause of death, and a modest hemorrhagic
      pancreatitis. DISCUSSION: Paroxetine is a selective serotonin reuptake inhibitor
      which stimulates antidiuretic hormone (ADH) release and may cause the syndrome of
      inappropriate ADH secretion with consecutive hyponatremia. Fluphenazine and
      haloperidol may contribute to this syndrome. Fluphenazine, and particularly
      olanzapine are associated with an increased incidence ofdiabetes. Olanzapine has
      been reported as a risk factor for acute pancreatitis. The Naranjo probability
      scale was not applicable because of almost immediate lethal outcome. CONCLUSION:
      Polypharmacy increases the risk of various adverse reactions. Adverse effects of
      paroxetine and many anti-psychotic drugs, such as hyponatremia and hyperglycemia,
      should be monitored periodically to prevent complications. The role of olanzapine
      in the etiology of acute pancreatitis remains to be evaluated.

PMID- 17542352
TI  - Lack of bioequivalence between generic risperidone oral solution and originator
      risperidone tablets.
AB  - Risperidone is an atypical anti-psychotic, available in various formulations.
      OBJECTIVE: The objective of the study was to compare the bioavailability of a
      generic oral solution of risperidone (Test formulation) and Risperdal tablets
      (Reference formulation). Both formulations contained 1 mg risperidone per dosing
      unit. METHODS: The study was carried out in 32 healthy volunteers under fasting
      conditions. Risperidone and 9-hydroxyrisperidone concentrations in plasma were
      determined using HPLC/MS/MS. RESULTS: The results show that the 90% confidence
      intervals for the geometric mean ratios of the solution and the tablet
      formulations were not within the acceptance range of 80 125% for risperidone,
      whereas the confidence intervals for 9-hydroxyrisperidone were within the
      acceptance range of 80 - 125%. CONCLUSION: Bioequivalence between the generic 1
      mg/ml risperidone solution and the originator tablet formulation was not proven
      in this study.

PMID- 17542353
TI  - Pharmacokinetic comparison of two 40 mg tablet formulations of citalopram using a
      new amperometric detection technique.
AB  - OBJECTIVES: To assess the bio-equivalence of two citalopram 40 mg tablet
      formulations (Lecital of the Jordan Sweden Medical and Sterilization Co. (JOSWE)
      as a test product, and Cipramil of Lundbeck (Denmark) as a reference product),
      and to develop a new high-performance liquid chromatography (HPLC) method using
      liquid-liquid extraction followed by addition of acid for the quantification of
      citalopram in human plasma. METHODS: A single-blind, randomized, single-dose, 2
      treatment, 2-period, 2-sequence, crossover bioequivalence study with a 20-day
      washout period in 24 healthy volunteers. The drug was administered with 240 ml of
      water after 10-h overnight fasting. After dosing, serial blood samples were
      collected for a period of 192 h. Plasma harvested from blood was analyzed for
      citalopram by a novel method using HPLC coupled with an electrochemical detector.
      The limit of quantitation of citalopram was 1.493 ng/ml. Matrix-based calibration
      curves were linear over the range 1.493 - 80.640 ng/ml for citalopram. RESULTS:
      The average bioavailability and pharmacokinetic parameters of the two citalopram
      tablets were as follows: peak plasma concentration Cmax was 35.0 +/- 10.04 ng/ml
      and 33.4 +/-7.80 ng/ml for Lecital and Cipramil, respectively. The time to peak
      plasma concentrations tmax were 3.81 +/- 1.18 and 4.08 +/- 1.54 h, while the
      plasma half-life (t1/2) values were 54.0 +/- 7.50 and 54.7 +/- 10.6 h. The area
      under the plasma concentration-time profiles AUCo-t were 1,820 +/- 582 ng x h/ml
      and 1,660 +/- 510 ng x h/ml, whereas the AUC0-infinity were 2,010 +/- 663 ng x
      h/ml and 1,850 +/- 577 ng x h/ml for Lecital and Cipramil, respectively. The 90%
      confidence intervals for test/reference ratio were found within the acceptable
      limits of 80 - 125%, consequently no significant difference was found between the
      test and reference. CONCLUSION: Based on the pharmacokinetic and statistical
      results, it was concluded that Lecital 40 mg tablets of JOSWE is bioequivalent to
      Cipramil 40 mg tablets of Lundbeck (Denmark).

PMID- 17542354
TI  - Doctor, Senator Tennessean, and now Diplomat: Bill Frist.

PMID- 17542355
TI  - Compliance with the NPI.

PMID- 17542356
TI  - Frozen reimbursements an insult to medical professionals.

PMID- 17542357
TI  - Toppling tobacco in Tennessee: TMA works to help loosen tobacco's deadly grip on
      the volunteer state.

PMID- 17542358
TI  - In a whiff of smoke: some thoughts on smoking.

PMID- 17542359
TI  - Sudden onset of food poisoning?

PMID- 17542360
TI  - Serving patients with disabilities: FAQs for doctors.

PMID- 17542361
TI  - Uncomplicating the process of provider enrollment.

PMID- 17542362
TI  - Increasing rates of infants hospitalized with pertussis.
AB  - INTRODUCTION: Four infant deaths in one year due to pertussis at our hospital
      prompted a retrospective chart review to determine the trends in pertussis
      hospitalizations in children < one year of age over the past 14 years. METHODS:
      All medical records from July 1988-June 2002 with pertussis-specific ICD-9 codes
      were reviewed. Subjects were included in the analysis if they were < one year of
      age, had positive pertussis tests, an epidemiological link to a laboratory
      confirmed case; or if they had cough > two weeks with paroxysms, inspiratory
      whoops or post-tussive vomiting. Demographic, clinical, laboratory, and hospital
      course data were collected. RESULTS: Of the 85 patients identified, 69 subjects
      met the inclusion criteria. Cases increased over the years with two cases
      detected from 1988-92, 22 from 1993-97, and 45 from 1998-2002 (p < 0.001). Mean
      age at admission was 71 days; 94 percent were < six mos. compared to children
      between six mos.-one yr. (p < 0.001). Mean birth weight was 3027g, with 17
      percent preterm. Most subjects (77 percent) had no pertussis immunizations.
      Presenting symptoms were paroxysmal cough 85 percent, cyanosis 68 percent, and
      apnea 52 percent. Oxygen was required in 35 percent, mechanical ventilation in 12
      percent, and extracorporeal membrane oxygenation (ECMO) in four percent because
      of uncontrolled pulmonary hypertension. All three subjects on ECMO died. Mean
      lymphocyte count was 46.3 thou/uL in survivors and 61.1 thou/uL in those who died
      (p = 0.001). CONCLUSIONS: The number of patients hospitalized with pertussis has
      significantly increased. Mortality was seen in infants < 3 mos. with pulmonary
      hypertension, pneumonia, and elevated lymphocyte counts. These data support the
      need for new immunization strategies to prevent pertussis disease in infants too
      young to have been immunized.

PMID- 17542363
TI  - Children, war, and terrorist acts.

PMID- 17542364
TI  - An ethicist's commentary on extending anticruelty laws.

PMID- 17542365
TI  - Effects of radiotherapy on pituitary corticotroph macrotumors in dogs: a
      retrospective study of 12 cases.
AB  - The efficacy of low doses of radiotherapy for the treatment of pituitary
      corticotroph macrotumors in dogs is evaluated retrospectively. Twelve dogs with
      pituitary-dependent hyperadrenocorticism and a large pituitary tumor treated with
      36 Gy of radiation were included. Radiation was delivered in 12 fractions of 3 Gy
      over a 4- to 6-week period. Effects of radiation therapy on tumor size were
      assessed by computed tomography scans; a decrease was observed in 11 dogs
      (decrease > 50% in 6 dogs). Three dogs were reirradiated due to major tumor
      regrowth or a lack of tumor decrease (mean total dose: 22 Gy given in 3-Gy
      fractions over 3 or 4 weeks). The mean and median survival times following the
      initiation of radiotherapy were 22.6 months (688 days) and 17.7 months (539
      days), respectively. These data are consistent with previous findings, based on
      high-dose radiation, showing that radiotherapy is a useful option for treating
      pituitary corticotroph macrotumors in dogs. Furthermore, computed tomography
      follow-up of the treated dogs demonstrates objectively the efficacy of
      radiotherapy against corticotroph tumors in dogs.

PMID- 17542366
TI  - Milk fever and alert downer cows: does hypophosphatemia affect the treatment
      response?
AB  - The purpose of this prospective cohort study was to identify factors that place a
      dairy cow with uncomplicated milk fever (MF) at significant risk of becoming an
      alert downer cow (ADC) and to verify if these factors could be used to predict
      treatment outcome. Recumbent MF cows were examined before treatment and 52 were
      excluded due to complications. In all, histories and pretreatment serum samples
      were taken and the serum of 86 cows was analyzed for electrolyte levels (calcium,
      phosphorus, magnesium, and potassium). In total, 36 of the 86 samples were from
      ADCs and 50 from animals that responded to MF treatment (MFT). A binary-two
      factor logistic model determined that a MF cow with a phosphorus pretreatment
      level of > or = 0.9 mmol/L was 12 times more likely not to become an ADC than one
      with a phosphorus level < 0.9 mmol/L (CI: 6.3,23.1). Also, a binary multivariable
      logistic regression analysis showed that a MF cow with a pretreatment calcium
      level > or = 1.7 mmol/L was 14 times more likely to become an ADC than one with a
      serum level < 1.7 mmol/L (CI: 2.0,98). Age and the other serum electrolytes were
      not statistically significant risk factors at the 0.05 level. The rigorous
      pretreatment examination and stringent adherence to protocol reduced ADC
      misclassification and fostered the strong association between single factor serum
      phosphorus levels and ADCs. By using a cutoff level of serum phosphorus at > or =
      0.9 mmol/L, a practitioner could correctly predict that 95% of the MFs would not
      become ADCs and, therefore, this level would be a useful pretreatment predictor.

PMID- 17542367
TI  - Use of an enzyme-linked immunosorbent assay in bulk milk to estimate the
      prevalence of Neospora caninum on dairy farms in Prince Edward Island, Canada.
AB  - This study evaluated the use of bulk milk as a diagnostic tool for estimation of
      herd-level Neospora caninum exposure in Atlantic Canada; it was used to estimate
      the prevalence of dairy farms with a within-herd N. caninum-seroprevalence > or =
      15% in Prince Edward Island (PEI). The variation over time of N. caninum
      antibodies in bulk milk is also reported. Skimmed bulk milk and individual serum
      samples were analyzed for N. caninum antibodies by using an enzyme-linked
      immunosorbent assay (ELISA). Bulk milk samples were collected in May 2004 (n =
      235), May 2005 (n = 189), and June 2005 (n = 235). The prevalence of dairy farms
      with a within-herd seroprevalence > or = 15% on PEI was 6.4% in May 2004. In May
      and June 2005, respectively, 10.1% and 10.2% of farms had a > or = 15% within
      herd seroprevalence. In 11 farms that were considered positive based on bulk milk
      samples, blood samples were collected from all adult cows in September 2005, in
      conjunction with a 4th bulk milk sample on the same day. The correlation
      coefficient between serology and bulk milk ELISA was 0.87. The results of this
      study demonstrate that the prevalence of N. caninum in dairy farms can be
      estimated by using a bulk milk ELISA.

PMID- 17542368
TI  - Bilateral occurrence of granulosa-theca cell tumors in an Arabian mare.
AB  - An Arabian mare was referred for right granulosa-theca cell tumor (GTCT)
      evaluation. The mare was presented 4.5 years later for a left GTCT, after
      successfully conceiving and delivering a normal foal in the interim. The
      concurrent or nonconcurrent occurrence of bilateral GTCT in mares appears to be
      rare.

PMID- 17542369
TI  - Treatment of canine pediatric Neospora caninum myositis following
      immunohistochemical identification of tachyzoites in muscle biopsies.
AB  - A 7-week-old Irish wolfhound was evaluated for an abnormal hind limb gait.
      Quadriceps muscle atrophy was pronounced and patellar reflexes were absent
      bilaterally. Neospora caninum myositis was diagnosed by histopathologic and
      serologic examination and immunohistochemical staining of muscle. Substantial
      clinical improvement was noted after 18 weeks of treatment with clindamycin.

PMID- 17542370
TI  - Eosinophilic cystitis in a female German wire-haired pointer.
AB  - A 7-month-old, intact female, German wire-haired pointer presented with a 3-week
      history of stranguria, pollakiuria, and dysuria that was nonresponsive to
      antibiotics. Two prior episodes of dysuria-stranguria appeared to respond to
      antibiotic therapy. Bladder wall biopsies revealed eosinophilic cystitis and the
      dog responded well to medical management.

PMID- 17542371
TI  - Standing enucleation in the horse: a report of 5 cases.
AB  - Enucleation was performed in 5 horses under local anesthesia and sedation with
      the horse standing. Minimal hemorrhage occurred during the surgical procedure,
      and there were no other reported complications. Standing enucleation is a surgery
      that is safe to perform in horses.

PMID- 17542372
TI  - Prevalence of Campylobacter spp isolated from grower-finisher pigs in Ontario.
AB  - This study aimed to establish the prevalence of Campylobacter spp. in 80 Ontario
      grower-finisher pig herds. Ninety-nine percent of the isolates yielded
      Campylobacter, C coli being the most common species detected. Control of this
      microorganism must rely on careful food processing and storage of pork, rather
      than on an on-farm approach.

PMID- 17542373
TI  - Step ostectomy as a treatment for varus deformity of a metatarsophalangeal joint
      in a 4.5-month-old colt.
AB  - A 4.5-month-old quarter horse colt was presented with severe right hind
      metatarsophalangeal varus, present since birth. On radiographs, it was determined
      that there was a 16 degree deviation with the pivot point at the distal physis of
      the 3rd metatarsal bone. A step ostectomy in the sagittal plane corrected the
      deformity.

PMID- 17542374
TI  - Improve your management with your complimentary CVMA practice diagnostic report.

PMID- 17542375
TI  - Stunning and killing cattle humanely and reliably in emergency situations--a
      comparison between a stunning-only and a stunning and pithing protocol.

PMID- 17542376
TI  - Diagnostic ophthalmology. Bilateral preganglionic Horner's syndrome.

PMID- 17542377
TI  - Rethinking social causes of psychosis.

PMID- 17542378
TI  - The contribution of social factors to the development of schizophrenia: a review
      of recent findings.
AB  - OBJECTIVE: To investigate recent evidence suggesting that social factors are
      causally related to the development of schizophrenia. METHOD: I conducted a
      sytematic review of MEDLINE to identify possibly relevant studies. The search was
      limited to peer-reviewed studies and review articles appearing in English
      language journals since 1996. Studies were included if they used standardized
      diagnostic criteria for schizophrenia or standardized assessment instruments for
      psychotic symptoms. RESULTS: Studies of migrants to western Europe provide
      compelling support for the notion that social factors contribute to the
      development of schizophrenia. Findings such as excessively high risk for
      schizophrenia in second-generation immigrants are difficult to explain solely in
      terms of biological or genetic factors. A growing number of studies implicate
      childhood exposure to social adversity as a risk factor for schizophrenia,
      although few studies have used prospective designs. The increased incidence of
      schizophrenia risk associated with urban birth and (or) urban upbringing suggests
      possible social causation, but these findings are more ambiguous. Thus far, no
      studies have explored actual mechanisms by which exposure to social factors might
      generate psychotic symptoms, although animal experiments suggest that social
      defeat or social exclusion may cause dopamine dysregulation or sensitization.
      CONCLUSIONS: The accumulating evidence suggesting a role for social factors in
      the development of schizophrenia arises primarily from studies of migrants
      conducted in Europe. The mechanisms by which social factors exert their influence
      remain unknown. Future investigations of social causation should clarify the
      temporal relation between exposure to social defeat and (or) social adversity and
      the development of psychotic symptoms.

PMID- 17542379
TI  - The social causes of psychosis in North American psychiatry: a review of a
      disappearing literature.
AB  - OBJECTIVE: To review the North American literature with respect to the role of
      social factors in the etiology of psychosis, including schizophrenia. METHOD:
      Relevant publications were identified through a search of MEDLINE from 1966 to
      2006. Identified studies and articles had to originate in Canada or the United
      States to be included in the review. Articles written prior to 1966 were
      identified by cross-referencing bibliographies and reference lists. Articles were
      considered relevant if they discussed ethnoracial or other social factors as
      being causal or contributing to the development of psychosis or schizophrenia.
      RESULTS: The relation between the etiology of psychosis and such social factors
      as poverty, migration, and racial discrimination has been neglected in the North
      American psychiatric literature for the last 40 years. In Canada and the United
      States, there is a dearth of research on these issues: the study of social causes
      of psychosis has been replaced by a focus on the clinical encounter, in which
      clinician bias is presumed to be responsible for widespread misdiagnosis of
      psychosis in minority (mainly African-American) populations. The reasons for
      neglecting social causes of psychosis in the North American psychiatric
      literature are obscure but may have to do with the rise of genetic-biological
      paradigms in recent decades. CONCLUSIONS: The neglect of social causes of
      psychosis in the North American psychiatric literature has been coincident with
      an increase in scholarly concern among European clinicians and researchers.
      Careful reading of the European literature may reveal helpful avenues for future
      investigation in the North American context. In addition, drawing on social
      science literature and methods may help to clarify mechanisms underlying poverty,
      migration, and racial discrimination that contribute to psychosis in vulnerable
      individuals and groups.

PMID- 17542380
TI  - Use of health care services for psychological distress by immigrants in an urban
      multicultural milieu.
AB  - OBJECTIVE: Research in the United States tends to attribute low rates of use of
      mental health services by immigrants to economic barriers. The purpose of our
      study was to examine this issue in the context of Canada's universal health care
      system. METHODS: A survey of the catchment area of a comprehensive clinic in
      Montreal interviewed random samples of 924 Canadian-born individuals and 776
      immigrants born in the Caribbean (n = 264), Vietnam (n = 234), or the Philippines
      (n = 278) to assess their health care use for somatic symptoms, psychological
      distress, and recent life events. RESULTS: Overall rates of use of medical
      services in the past year were similar in immigrant (78.5%) and nonimmigrant
      (76.5%) groups. Rates of use of health care services for psychological distress
      were significantly lower among immigrants (5.5% compared with 14.7%, P < 0.001).
      This difference was attributable both to a lower rate of use of specialty mental
      health services by immigrants (2.5% compared with 11.7%, P < 0.001) and to
      differential use of medical services for psychological distress (3.5% compared
      with 5.8%, P = 0.02). When level of psychological distress was controlled,
      Vietnamese and Filipino immigrants were one-third as likely as Canadian-born
      residents to make use of mental health services. The lower rate of use by
      immigrants could not be explained by differences in sociodemographics, somatic or
      psychological symptoms, length of stay in Canada, or use of alternative sources
      of help. CONCLUSION: Immigrant status is associated with lower rates of use of
      mental health services, even with universal health insurance. This lower rate of
      use likely reflects cultural and linguistic barriers to care.

PMID- 17542381
TI  - Prevalence of mental disorders and associated service variables among Ontario
      children who are permanent wards.
AB  - OBJECTIVE: To identify the prevalence rate of mental disorders among Ontario
      children who are permanent wards and also the key practice and descriptive
      variables associated with their diagnostic status. METHOD: I reviewed case files
      from a stratified random sample of 429 Ontario children who were permanent wards
      with no access to biological parents on December 31, 2003. Data abstracted from
      files included information on descriptive variables (such as age, sex, and type
      of permanent ward), all disorders (that is, mental and other current medical
      diagnoses and disabilities), family history, maltreatment experiences, service
      history (such as age at admission to care and current residential placement
      type), and permanency plans. RESULTS: The prevalence of mental disorders was
      31.7%. A significantly higher proportion of children with mental disorders
      experienced maltreatment. Children with mental disorders were almost 3 times more
      likely than those without mental disorders to be placed by Children's Aid
      Societies in privately operated resources, such as group homes, and almost 10
      times less likely to be living in a probationary adoption home. Although children
      with mental disorders were less likely to have a permanency plan of adoption than
      were children without mental disorders, regression analysis found that only 2
      variables--age on becoming a permanent ward and age at the time of the study-
      were predictive of children's adoption plans. CONCLUSIONS: The findings support
      the need for improved monitoring of the aggregate mental health needs of children
      who are permanent wards. Numerous implications for service delivery and future
      research are discussed.

PMID- 17542382
TI  - Problematic physicians: a comparison of personality profiles by offence type.
AB  - OBJECTIVE: This exploratory study compares objective personality test findings
      among physicians exhibiting different forms of misconduct. The importance of
      delineating distinctive personality characteristics by type of offence is that
      such characterizations can direct therapy and prognosis for remediation. METHOD:
      Eighty-eight physicians referred to the Vanderbilt Comprehensive Assessment
      Program for Professionals (V-CAP) completed the Minnesota Multiphasic Personality
      Inventory-2, the Personality Assessment Inventory, or both, as part of their
      evaluation. On the basis of referral information, physicians were partitioned
      into 3 groups of offenders: "sexual boundary violators," "behaviourally
      disruptive," and "other misconduct." RESULTS: On both personality measures, the
      sexual boundary violators generated the greatest percentage of profiles
      indicative of character pathology. CONCLUSIONS: Although all 3 groups exhibited
      unacceptable behaviours, the pervasive personality features of the sexual
      boundary violators are associated with greater therapeutic challenge, and these
      individuals likely pose the greater risk of reoffending.

PMID- 17542383
TI  - Comorbidity with ADHD decreases response to pharmacotherapy in children and
      adolescents with acute mania: evidence from a metaanalysis.
AB  - OBJECTIVE: To assess whether comorbid attention-deficit hyperactivity disorder
      (ADHD) influences response to treatment in young patients with acute mania.
      METHODS: We conducted a metaanalysis of 5 open trials of 100, 35, 41, 60, and 37
      children and adolescents. The pooled group included 273 children and adolescents
      with bipolar disorder (BD), divided into 2 subgroups: those with (n = 132), and
      those without (n = 141), ADHD comorbidity. RESULTS: There was a moderate and
      significant reduction in relative risk (RR) favouring treatment response in
      children and adolescents with BD but without ADHD comorbidity (RR 0.822; 95% CI,
      0.69 to 0.97; P = 0.021). The negative effect of ADHD comorbidity on treatment
      response was more significant in studies including adolescents only or subjects
      with BD I only. CONCLUSION: These findings suggest that children and adolescents
      with BD and ADHD tend to be less responsive to drugs used in treatment of acute
      mania.

PMID- 17542384
TI  - The Montreal Cognitive Assessment: validity and utility in a memory clinic
      setting.
AB  - OBJECTIVE: To prospectively validate the Montreal Cognitive Assessment (MoCA) in
      a UK memory clinic. METHOD: We administered the MoCA and Mini-Mental State
      Examination (MMSE) to 32 subjects fulfilling diagnostic criteria for dementia, to
      23 subjects fulfilling diagnostic criteria for mild cognitive impairment (MCI),
      and to 12 memory clinic comparison subjects, at baseline and then at 6-month
      follow-up. Clinical diagnoses for dementia and MCI were made according to ICD-10
      and Petersen criteria. The sensitivity and specificity of both measures were
      assessed for detection of MCI and dementia. RESULTS: With a cut-off score of 26,
      the MMSE had a sensitivity of 17% to detect subjects with MCI, whereas the MoCA
      detected 83%. The MMSE had a sensitivity of 25% to detect subjects with dementia,
      whereas the MoCA detected 94%. Specificity for the MMSE was 100%, and specificity
      for the MoCA was 50%. Of subjects with MCI, 35% developed dementia within 6
      months, and all scored less than 26 points on the MoCA at baseline. CONCLUSIONS:
      The MoCA is a useful brief screening tool for the detection of mild dementia or
      MCI in subjects scoring over 25 points on the MMSE. In patients already diagnosed
      with MCI, the MoCA helps identify those at risk of developing dementia at 6-month
      follow-up.

PMID- 17542385
TI  - Re: Illicit opioid use and its key characteristics: a select overview and
      evidence from a Canadian multisite cohort of illicit opioid users.

PMID- 17542386
TI  - The gritty reality. . .

PMID- 17542387
TI  - Re: Avoiding the use of agency staff in the operating department.

PMID- 17542388
TI  - FM transmitters in the operating theatre.

PMID- 17542389
TI  - Barriers to effective pain management.
AB  - In this article my sole aim is to engage the reader to think about the management
      of pain in a different way. I have deliberately taken a less formal style but
      provided references if you are interested in following up. The management of pain
      has often been assumed to be a routine part of care, in fact in the perioperative
      arena it is the second most common nursing intervention (Juntilla et al 2005).
      Despite this activity, pain after surgery has been reported to be a consistent
      problem which has spanned several decades (Marks & Sachar 1973, Wu et al 2002,
      Ekstein et al 2006). The reasons for this are well documented and include:
      patient barriers, inadequate knowledge of healthcare professionals, lack of
      assessment and organisational practices which impede the administration of
      analgesics and non-pharmacological interventions. Despite this knowledge the
      changes required in practice are not necessarily forthcoming. The purpose of this
      paper is to explore the patient, professional and organisational barriers which
      affect the optimal management of pain in the perioperative period, and provide
      some practical solutions to help you think about and manage pain more
      effectively.

PMID- 17542390
TI  - Conscientious objection: justified or just refusal to care?
AB  - In general terms, healthcare professionals are not at liberty to refuse to care
      for any patient (UKCC 2004). However, as the law permits patients to do what is
      morally and ethically right for them with regard to termination of pregnancy, it
      must also extend this right to the healthcare professional. The Abortion Act
      (1967, Section 4 (i)) permits healthcare professionals to refuse participation on
      the grounds of conscientious objection. As there is no statutory definition of
      conscientious objection, it is left to the individual to prove that they have an
      objection to being involved in terminations of pregnancy.

PMID- 17542391
TI  - Surgical glove practice: the evidence.
AB  - Surgical gloves are worn to protect both the patient and the surgical team from
      transferred infections. Wearing two pairs of gloves, perforation indicator
      systems, glove liners, knitted gloves and triple gloving are said to offer
      additional protection. This paper presents the main findings from a Cochrane
      systematic review of 30 trials examining surgical gloving practice.

PMID- 17542392
TI  - Lister's sinus forceps.
AB  - There is little doubt that Joseph Lister (1827-1912) was the greatest surgical
      benefactor to mankind. His name is perpetuated in our theatres, wards and
      accident departments every time we use that humble but very useful instrument,
      his sinus forceps.

PMID- 17542393
TI  - Workers' comp: patience and collaboration needed.

PMID- 17542394
TI  - "They deserve nothing less".

PMID- 17542395
TI  - Defusing a time bomb: TMA leadership impacts border health.

PMID- 17542396
TI  - Establishment of the United States-Mexico Border Health Commission.

PMID- 17542397
TI  - Tuberculosis among Mexican-American immigrants.

PMID- 17542398
TI  - Border pandemic influenza planning and response efforts.

PMID- 17542399
TI  - Estimated prevalence of hyperinsulinemia among Mexican-American adolescents in
      south Texas.

PMID- 17542400
TI  - Infectious disease and the adolescent immigrant.

PMID- 17542401
TI  - Exotic disease in the migrant patient.

PMID- 17542402
TI  - Commentary: missed opportunities and lessons learned.

PMID- 17542403
TI  - Telemedicine demonstration projects along the Texas-Mexico border.

PMID- 17542404
TI  - Serum her-2/neu and survivin levels and their relationship to histological
      parameters in early-stage breast cancer.
AB  - This study was conducted to investigate the serum levels of her-2/neu and
      survivin in patients with early-stage breast cancer and their relationship with
      known histological parameters. Forty-one patients with early-stage breast cancer
      were investigated. Serum samples were collected from patients on their first
      admission before adjuvant chemotherapy, and from healthy controls. Serum her
      2/neu and survivin levels were determined using an enzyme-linked immunosorbent
      assay. There was no difference in the levels of serum her-2/neu and survivin
      between the breast cancer patients and the control group. Serum her-2/neu
      concentration showed moderate correlations with disease stage and the Ki-67
      level, and the serum survivin level showed a moderate correlation with
      progesterone receptor concentration. Serum levels of her-2/neu and survivin were
      not significantly related to age and histological parameters in patients with
      early-stage breast cancer. However, much research continues on the prognostic
      value of serum her-2/neu and survivin levels, and important new knowledge may
      ultimately emerge.

PMID- 17542405
TI  - Neutralizing antibodies to interferon beta-1b are not associated with disease
      worsening in multiple sclerosis.
AB  - The clinical impact of neutralizing antibodies (NAbs) on interferon beta
      (IFNbeta) efficacy was studied in three large patient cohorts comprising 6698
      multiple sclerosis (MS) patients receiving IFNbeta-1b across North America,
      Europe, and Australia. In North America and Europe, NAb testing was generally
      undertaken because of a poor clinical response; in Australia, it was mandatory
      for every patient. Of the 6697 patients tested, 28.9% had at least one NAb titre
      > or = 20 neutralizing units (NU)/ml, 14.4% had NAb titres > or = 100 NU/ml and
      7.7% had NAb titres > or = 400 NU/ml. The NAb-positive rate of 37.0% in Australia
      was significantly greater than those in North America (21.3%) and Europe (27.6%),
      and this was observed at every NAb titre level. Our results suggest that NAbs are
      not responsible for poor clinical responses and that NAb status is of little
      clinical value. These findings will need to be confirmed in a large independent
      study.

PMID- 17542406
TI  - Leucocyte-depleted blood cardioplegia.
AB  - The effect of the depletion of leucocytes from cardioplegic and initial
      myocardial reperfusion blood on the inflammatory response and myocardial
      protection in patients with unstable angina undergoing cardiopulmonary bypass
      (CPB) was studied. Patients were allocated randomly to a leucocyte-depleted (LD)
      group or a control group. The LD group received continuous retrograde LD
      isothermic blood cardioplegia and the control group received isothermic blood
      cardioplegia. Blood samples were collected at seven time-points before, during
      and after the procedure. Total leucocyte counts of cardioplegia blood in the LD
      group were significantly lower than in the control group, but systemic leucocyte
      and neutrophil counts after CPB did not differ between the groups. The levels of
      adhesion molecules, cytokines, elastase and malondialdehyde were significantly
      increased after CPB in both groups and reached peak values 2-6 h after surgery;
      no other significant differences were found. LD cardioplegia and myocardial
      reperfusion did not attenuate the endothelial and neutrophil-mediated components
      of the CPB-induced inflammatory response, which may lead to myocardial
      reperfusion injury.

PMID- 17542407
TI  - Effect of Saccharomyces boulardii in children with acute gastroenteritis and its
      relationship to the immune response.
AB  - We evaluated the effect of Saccharomyces boulardii administration in otherwise
      healthy children aged between 6 months and 10 years who were admitted for acute
      diarrhoea (15 males, 12 females). The patients were randomized into two groups:
      group 1 (n = 16) received 250 mg S. boulardii dissolved in 5 ml of water orally
      twice daily for 7 days and group 2 (n = 11) received placebo. Clinical and
      laboratory assessments were performed on admission and on day 7 of follow-up.
      Both groups experienced reduced daily stool frequency, the decrease being
      significantly greater in group 1 on days 3 and 4 compared with group 2. Group 1
      demonstrated significant increases in serum immunoglobulin A and decreases in C
      reactive protein levels on day 7. The percentage of CD8 lymphocytes on day 7 was
      significantly higher in group 1 than group 2. This study confirmed the efficacy
      of S. boulardii in paediatric acute gastroenteritis and the findings suggest that
      S. boulardii treatment enhances the immune response.

PMID- 17542408
TI  - Evaluation of the efficiency of medical masks and the creation of new medical
      masks.
AB  - The effectiveness of medical masks in preventing respiratory infection was
      investigated by testing bacterial leakage, filtration efficiency, respiratory
      resistance and oxygen concentration of the enclosed space. Polypropylene (PP)
      fibres were treated with dimethyldioctadecylammonium bromide to impart a positive
      electrical charge capable of attracting bacteria. The fluffed PP fibres were used
      to make a polypropylene mask and to edge standard surgical and N-95 respirators
      to prevent leakage. A PP napkin was created by melting and blowing PP. The PP
      edging seal dramatically reduced bacterial leakage of standard masks and was more
      effective than adhesive paper tape edging in reducing respiratory resistance.
      Bacterial or viral filtration efficiency was almost 100% for the PP mask and the
      PP napkin. The specially designed PP mask with a synthetic adhesive at the edge
      of the mask may be more effective than the standard surgical mask and the N-95
      respirator. The PP napkin is an important tool in preventing the spread of
      pathogens.

PMID- 17542409
TI  - BCL6 gene mutations in transitional cell carcinomas.
AB  - The B-cell lymphoma-6 (BCL6) gene was initially identified at a translocation
      site observed frequently in diffuse large B-cell lymphomas. In the present study,
      BCL6 mutations at the 5' non-coding region in 47 cases of transitional call
      carcinoma (TCC) were analysed using polymerase chain reaction-single-strand
      conformation polymorphism. The results were compared with data obtained
      previously by immunohistochemical staining for the BCL6 protein. Overall, BCL6
      mutations were observed in 44.7% of cases. Mutation of the 5' non-coding region
      was not correlated with histological grade of the tumour; however, the better the
      histological grade, the greater the mutation rate of the E1.12 fragment. The BCL6
      mutation occurred independently of over-expression of the protein. The BCL6 gene
      mutation and the protein expression were detectable in a large proportion of
      TCCs. BCL6 protein over-expression as well as BCL6 gene mutation of the E1.12
      fragment may play an important role in the morphological differentiation of TCC.

PMID- 17542410
TI  - Standardized uptake values of normal organs on 18F-fluorodeoxyglucose positron
      emission tomography and computed tomography imaging.
AB  - Standardized uptake values (SUVs) of normal organs were evaluated by 18F
      fluorodeoxyglucose (18F-FDG) positron emission tomography and computed tomography
      (PET-CT) scanning. Seventy patients (38 men and 32 women) with no non
      physiological 18F-FDG uptake participated in the study. All patients fasted for
      at least 4 h before PET-CT imaging and their fasting blood glucose levels were
      within the normal range. Image acquisition was performed after intravenous
      administration of 18F-FDG and images were obtained from the vertex to the upper
      thigh region. The SUVs of various organs were determined from the transverse
      views. The uptake of 18F-FDG was highest in the cerebrum, cerebellum, myocardium,
      tonsils, liver and spleen in both sexes. Having knowledge of the physiological
      uptake of 18F-FDG and normal organ SUVs is required for the correct
      interpretation of whole-body 18F-FDG-PET-CT studies.

PMID- 17542411
TI  - Immunohistochemical analysis of PCNA, Ki67 and p53 in nasal polyposis and
      sinonasal inverted papillomas.
AB  - Immunoreactivity of proliferating cell nuclear antigen (PCNA), Ki67 and p53 in
      inflammatory nasal polyp and inverted papilloma tissues was investigated.
      Immunohistochemistry was performed using a standard avidin-biotin-peroxidase
      method, and the immunoreactivity of PCNA, Ki67 and p53 was quantified by counting
      immunostained nuclei in at least 1000 epithelial cells. The mean labelling index
      (percentage of immunostained cells) for PCNA was 40.68 in the inverted papilloma
      group and 14.73 in the nasal polyp group, and for Ki67 was 15.43 in the inverted
      papilloma group and 2.64 in the nasal polyp group. Both of these differences
      between the inverted papilloma and nasal polyp groups were significant.
      Immunoreactivity for p53 was detected in five (35.7%) inverted papilloma patients
      and two (9.5%) nasal polyp patients. The increase in epithelial cell
      proliferation seemed to be greater in inverted papillomas than in inflammatory
      nasal polyps. Increased epithelial cell proliferation may be involved in the
      development of inverted papillomas.

PMID- 17542412
TI  - Monitoring vaccination coverage in Istanbul using the lot quality assurance
      sampling and geographic information system.
AB  - The quality of vaccination services provided for children aged 12-23 months was
      determined in different districts of Istanbul, Turkey. Quality was assessed
      through a lot quality assurance sampling method, using data extracted from
      interviews conducted in 2001 with the mothers or carers of the children.
      Concurrently, geographic information system technology was used for integrated
      evaluation of the data from different lots and for presentation of the results as
      thematic maps. The results of this study helped to identify districts of the city
      in which vaccination services were below the expected level of quality and where
      an unacceptable number of children were not being fully vaccinated. Subsequent to
      this study, actions were taken by the agencies responsible to improve the
      coverage and quality of the vaccination services in these districts of Istanbul.

PMID- 17542413
TI  - Antimicrobial resistance and serotypes of nasopharyngeal strains of Streptococcus
      pneumoniae in Chinese children with acute respiratory infections.
AB  - This prospective, multicentre, nasal carriage study in Chinese children with
      upper respiratory infection was carried out over the period from 2000 to 2002.
      Overall, the prevalence of pneumococcal carriage was 24.9%. Antimicrobial
      susceptibility tests were performed for 887 isolates of Streptococcus pneumoniae
      of which 33.5% were intermediately susceptible to penicillin and 6.4% were
      resistant. Multidrug resistance was very common. Pneumococcal strains (n = 625)
      were serotyped, showing 72.2% were covered by the 23-valent pneumococcal
      polysaccharide vaccine and 57.6% by the seven-valent pneumococcal conjugate
      vaccine. Serogroups 19 and 23 were significantly associated with penicillin
      resistance, which is increasing in China. Erythromycin, tetracycline and
      sulphamethoxazole/trimethoprim cannot be recommended as first-line treatments for
      respiratory tract infection as in some other developing countries. These features
      of serotype distribution are of importance for surveillance in the era of the new
      conjugate vaccine. In particular, these features will allow for documentation of
      serotype replacement after the introduction of widespread vaccination.

PMID- 17542414
TI  - Post-operative blood salvage and retransfusion in total hip and knee
      arthroplasty.
AB  - This retrospective study evaluated the safety and efficacy of post-operative
      blood salvage and retransfusion in 430 patients undergoing total hip arthroplasty
      and 530 patients undergoing total knee arthroplasty. Volumes of autologous blood
      retransfused (mean +/- SD) were 525 +/- 75 and 660 +/- 95 ml in the hip and knee
      replacement groups, respectively. Overall, 230 patients (24%) also required
      allogeneic blood transfusion. In a subgroup of 150 randomly selected patients,
      the values of free haemoglobin in the allogeneic, autologous and patients' blood
      at the time of surgery were 0.568 +/- 0.112, 0.272 +/- 0.067 and 0.032 +/- 0.011
      g/l, respectively. On the first and third post-operative days, the levels in
      patients' blood were 0.092 +/- 0.039 and 0.057 +/- 0.028 g/l, respectively. There
      were no major complications; transient chills and fever were reported in 99
      (10.3%) and 115 patients (12.0%), respectively. In conclusion, post-operative
      blood salvage and retransfusion is a safe way to reduce the need for allogeneic
      blood transfusion in patients undergoing elective orthopaedic surgery.

PMID- 17542416
TI  - Re: JRSH governance special issue, 2007;127(2).

PMID- 17542417
TI  - Policy and politics.

PMID- 17542418
TI  - In practice. Interview by Jacob Lonsdale.

PMID- 17542419
TI  - A sporting chance.

PMID- 17542420
TI  - What's in it for the eastender?

PMID- 17542421
TI  - London Olympics 2012: 'the catalyst that inspires people to lead more active
      lives'?

PMID- 17542422
TI  - The perspective of syndromic surveillance systems on public health threats: a
      paradigm of the Athens 2004 Olympic Games.

PMID- 17542423
TI  - London 2012: occupational health in the construction programme.
AB  - This article explores the approach to occupational health in the UK construction
      industry in both broad and narrow contexts. The construction programme for the
      2012 Olympic Games and Paralympic Games includes the creation of a large urban
      park in east London containing many sports venues and served by enhanced
      infrastructure. The Olympic Delivery Authority (ODA), responsible for the
      construction programme, is developing plans that seek to assure the health of the
      thousands of workers who will be engaged in this work. Such plans are not being
      drafted in a vacuum. In addition to considerable consultation with stakeholders
      the ODA is also drawing on some of the exciting work that has been undertaken in
      occupational health in recent years. In particular, the move from a focus on
      technical health services provided by 'experts' to an acceptance that health
      issues should be managed within employing organizations. Understanding this broad
      context provides a solid basis for analysing the specific proposals for
      occupational support during the Olympic Park construction.

PMID- 17542424
TI  - Sustainable legacies for the 2012 Olympic Games.
AB  - The London 2012 Olympic and Paralympic Games have the unique potential to deliver
      sustainable sporting, social, cultural, economic and environmental legacies, not
      just for London as the host city, but for the whole of Britain. This article
      focuses primarily on the first three of these potential Olympics legacies. The
      first area explored is the social legacy as it impacts on host communities;
      second, the potential educational and cultural legacy of the 2012 Games are
      examined; and finally, there follows an overview of the health benefits that
      could result from a sustained increase in mass participation in sport, physical
      activity and exercise. This appraisal is undertaken through a review of existing
      Olympic literature and examples are drawn from previous summer and winter Games.
      This preliminary exploration is followed by the identification of some key
      challenges to be overcome if the opportunities available to a wide and diverse
      range of stakeholders are to be fully optimized. The article suggests that the
      2012 Games can act as a catalyst for sports development throughout Britain, while
      also assisting with government cross-cutting agendas such as tackling crime,
      antisocial behaviour, developing healthy and active communities, improving
      educational attainment, and combating barriers to participation. In doing so,
      this article argues that priority should be placed at supporting grassroots sport
      through greater access to sport in the community, and not solely elite level
      sports development. The article concludes by suggesting that the 2012 Games
      provide opportunities to deliver real and tangible changes and most importantly,
      to afford a higher priority to sport, along with the obvious associated health
      benefits for Britain as a whole. The underlying challenge as we move towards 2012
      is to achieve a positive step change in the attitudes towards sport and physical
      activity in British society. Achieving this would possibly be the greatest legacy
      of the 2012 Olympic and Paralympic Games.

PMID- 17542425
TI  - Mass sport policy development in the Olympic City: the case of Qingdao--host to
      the 2008 sailing regatta.
AB  - The Olympic Games have emerged as a significant catalyst of urban change and
      leave numerous legacies to the cities and countries that host them. This article
      will address the impacts of the preparations for the 2008 Olympic sailing regatta
      on mass sport development in the host municipal city of Qingdao, China, and
      examine the government's mass sport policy and development interventions that are
      linked to the 2008 Olympic Bid and subsequent preparations. The research draws on
      policy-making theory to unravel the nature of change and development of mass
      sport in Qingdao, especially how national and local governments create new
      policies to promote mass sport development in Qingdao and persuade people to take
      regular physical activity and practise sports to improve health. The article
      indicates that the preparations for the event generate significant improvements
      in mass sport in Qingdao, such as the development of mass sport policies,
      increase in sports participation rates, creation of new sporting facilities, and
      consequent improvement of public health. Nevertheless, negative effects are also
      evidenced in the greater imbalance between rural and urban sports development,
      and the high fees for using the new water sports facilities.

PMID- 17542426
TI  - Access for all: the rise of the Paralympic Games.
AB  - The Paralympic, or Parallel, Games for athletes with disabilities have played a
      major role over the past half century in changing attitudes towards disability
      and accelerating the agenda for inclusion. This article charts their development
      from small beginnings as a competition for disabled ex-servicemen and women in
      England founded shortly after the Second World War to the present day ambulatory
      international festival of Summer and Winter Games organized in conjunction with
      the Olympic Games. The Paralympic Games trace their origins to the work of Dr
      (later Sir) Ludwig Guttmann at the National Spinal Injuries Unit at Stoke
      Mandeville Hospital in Buckinghamshire who used sport as an integral part of the
      treatment of paraplegic patients. A sports competition was held at the hospital
      to coincide with the Opening Ceremony of the London Games in July 1948. This
      became an annual event attracting the first international participation in 1952,
      after which it became the International Stoke Mandeville Games. From 1960 onwards
      attempts were made to hold every fourth Games in the Olympic host city. Despite
      initial success in staging the 1960 Games in Rome and the 1964 Games in Tokyo,
      subsequent host cities refused to host the competitions and alternative locations
      were found where a package of official support, finance and suitable venues could
      be assembled. In 1976, the scope of the Games was widened to accept other
      disabilities. From 1988 onwards, a process of convergence took place that saw the
      Paralympics brought into the central arena of the Olympics, both literally and
      figuratively. In the process they have embraced new sports, have encompassed a
      wider range of disabilities, and helped give credence to the belief that access
      to sport is available to all. The Paralympics also underline the change from
      sport as therapeutic competition to that of elite events that carry intrinsic
      prestige, with growing rivalry over medal tables. For the future, however,
      questions remain as to whether the current arrangements of separate but
      supposedly equal festivals assist the continuing development of the Paralympics
      or perpetuate difference.

PMID- 17542427
TI  - [Coronary CT scan: the best indications at present].

PMID- 17542428
TI  - [Clinical and angiographic parameters affecting the quality of 16 slice spiral CT
      in the diagnosis of restenosis after stenting the left main coronary artery].
AB  - The metallic component of coronary stents makes it difficult to study their lumen
      by angio scanner. The object of this preliminary study was to appreciate the
      factors influencing the diagnosis of restenosis after stenting the left main
      coronary artery by 16-slice spiral angio CT. This Monocentric study included 27
      patients who underwent 16-slice spiral angio CT six months after stenting of the
      left main coronary artery. It was possible to assess the stent lumen in 21
      patients (78%) and no cases of > 50% restenosis were observed. In 4 patients,
      hypodense zones adjacent to the stent links were observed suggesting moderate
      intimal hyperplasia. The tests for ischaemia were normal in 3 of these patients.
      Coronary angiography and endocoronary ultrasound excluded significant restenosis
      in the fourth patient. In univariable analysis, the facors associated with good
      or excellent angioscanner quality (45% of patients) were Ostial stenosis (p =
      0.03), no or minimal calcification on initial coronary angiography (p = 0.0S),
      stent diameters > 3.5mm (p = 0.03), heart rates < 60/min (p = 0.04), absence of
      extrasystoles (p = 0.05) during acquisition. In multivariable analysis, the only
      significant factors were absent or minimal calcification and stent diameters >
      3.5mm (p = 0.02). The multidetector scanner seems a very promising method of
      investigating patients who have undergone stenting of the left main coronary
      artery but this study shows that certain clinical and angiographic parameters are
      limiting factors of surveillance with a 16-slice angioscanner.

PMID- 17542429
TI  - [Activation of cardiac caspases: a double-edged weapon implicated in cardiac
      dysfunction].
AB  - Low dead cell levels detected in various cardiac pathologies led to consider
      cardiac apoptosis as epiphenomena without repercussion on heart function.
      However, apoptosis prevention, and more specifically caspase inhibition, has been
      associated with major myocardial contractile performance improvement. This review
      describes specifically caspase involvement in myocardial dysfunction and
      highlights typical cardiomyocyte apoptosis signaling features. Thus caspase
      neutralization may represent a promising therapeutic strategy in heart disease
      treatments.

PMID- 17542430
TI  - Optic nerve head, retinal nerve fiber layer, and macular thickness
      characteristics on optical coherence tomography in optic disk hypoplasia.

PMID- 17542431
TI  - Scleral perforation during strabismus surgery in cryotherapy-treated retinopathy
      of prematurity.

PMID- 17542432
TI  - Diplopia lasting more than 8 months.

PMID- 17542433
TI  - Retinopathy of prematurity: the relationship between the pediatric
      ophthalmologist and the hospital.

PMID- 17542434
TI  - Lisch nodules associated with neurofibromatosis type 1.

PMID- 17542435
TI  - Anterior transposition of the inferior oblique for dissociated vertical
      deviation.

PMID- 17542436
TI  - Intermittent exotropia.
AB  - This article describes the clinical manifestations of and management options for
      intermittent exotropia. Control of the strabismus is one of the parameters that
      can be assessed for all children with the condition. A method of quantifying
      control, the Newcastle Control Score, is presented.

PMID- 17542437
TI  - Evaluation of the effectiveness of anterior transposition of the inferior oblique
      muscle in dissociated vertical deviation with or without inferior oblique
      overaction.
AB  - PURPOSE: Anterior transposition of the inferior oblique muscle (ATIO) has been
      reported to be an effective treatment for dissociated vertical deviation (DVD).
      In this study, we evaluated the effectiveness of this surgical procedure in
      patients with DVD alone and in those with DVD with concurrent overactive inferior
      oblique muscle and compared the results. METHODS: Nineteen eyes with DVD alone
      (group 1) and 15 eyes with DVD and concurrent inferior oblique overaction (group
      2) underwent ATIO. The amount of DVD and inferior oblique overaction before and
      after the operation was measured and statistically analyzed. RESULTS: The average
      follow-up time for group 1 and group 2 was 9.4 and 9.0 months, respectively. Of a
      total of 34 eyes, 7 had DVD of more than 15 prism-diopters (pd) [four eyes from
      group 1 and three eyes from group 2] in which the residual DVD after surgery was
      more than 5 pd. However, in the 27 eyes with DVD of 15 pd or less (15 from group
      1 and 12 from group 2), the residual DVD after the operation was less than 5 pd.
      (Fisher's exact test, P = .014). CONCLUSION: ATIO is an effective method for
      correcting DVD with and without inferior oblique overaction, especially in
      deviations of less than 15 pd.

PMID- 17542438
TI  - Long-term outcome of a silicone expander for Brown's syndrome.
AB  - PURPOSE: Assessment of the long-term outcome of a silicone tendon expander for
      Brown's syndrome. PATIENTS AND METHODS: Records of 22 eyes of 16 patients with
      the diagnosis of Brown's syndrome were reviewed. Patients who had previous
      superior oblique (SO) muscle surgery or previous or concurrent surgery on another
      muscle were not included. The average follow-up period was 58.4 months. The SO
      tendon was cut approximately 5 mm away from the nasal border of the superior
      rectus muscle. The expander, which varied from 5 to 7 mm in length, was placed in
      the tenotomized SO muscle tendon. RESULTS: Elevation in adduction was obtained in
      all patients who underwent surgery. One eye had undercorrection, one eye had
      limitation in downgaze, and three eyes had overcorrection postoperatively. Six
      eyes had a severe postoperative inflammatory reaction that was successfully
      treated with topical corticosteroids and oral nonsteroidal anti-inflammatory
      drugs. Six eyes had foreign body sensation that resolved in time. In two eyes,
      consecutive SO palsy developed. One eye was reoperated for extrusion and the
      silicone bands were removed from two eyes; these eyes improved in 2 to 4 months.
      CONCLUSION: Silicone expander surgery is a challenging procedure used to treat
      Brown's syndrome. No cyclotorsion occurred after this surgery. This procedure is
      reversible and repeatable. A learning period is required to obtain the skill
      needed to avoid entering the sub-Tenon space.

PMID- 17542439
TI  - Effect of diode laser retinal ablative therapy for threshold retinopathy of
      prematurity on the visual field: results of goldmann perimetry at a mean age of
      11 years.
AB  - PURPOSE: To assess the peripheral visual field in premature children who received
      diode laser photocoagulation for threshold retinopathy of prematurity (ROP) and
      in a comparison group with subthreshold ROP that had regressed spontaneously
      without laser treatment. PATIENTS AND METHODS: Eleven patients (18 eyes) were
      treated with laser, and nine patients (16 eyes) with subthreshold untreated ROP
      were recalled for assessment at a mean follow-up of 11 years. All children
      underwent Goldmann visual field testing using the II4e and V4e stimuli. Distance
      visual acuity measurement, dilated fundal examination, and cycloplegic
      autorefraction were also performed. RESULTS: The visual field extent in treated
      eyes was 3% to 4% smaller for the V4e target and 7% to 10% smaller for the II4e
      target than in the comparison eyes. For the II4e stimulus, the right eye visual
      field extent of the laser-treated children did not differ significantly from that
      of the untreated comparison group (P = .11), but the left eyes showed a
      borderline significant reduction (P = .046). For the larger V4e stimulus, no
      significant differences were noted (right eye, P = .41; left eye, P = .30).
      CONCLUSIONS: This is the first study to assess the effect of diode laser therapy
      on the peripheral visual field in eyes with threshold ROP using Goldmann
      perimetry. Laser-treated eyes showed a slight constriction of peripheral visual
      fields compared with untreated subthreshold eyes. It is uncertain whether this
      was due to the laser treatment itself or to the more severe ROP in the laser
      group. However, the limited reduction in visual field extent is comparable to
      that reported for cryotherapy and is unlikely to be of functional significance.

PMID- 17542440
TI  - Association between fixation preference testing and strabismic pseudoamblyopia.
AB  - PURPOSE: Fixation preference testing is the mainstay of clinical diagnosis of
      strabismic amblyopia in preverbal children and infants. The purpose of this study
      is to evaluate the strength of the association between fixation preference and
      strabismic amblyopia. PATIENTS AND METHODS: Eighty patients (3 to 8.3 years) with
      manifest strabismus and the capability to cooperate with a Snellen acuity test
      were prospectively examined. Thirty patients were diagnosed as having partially
      accommodative esotropia, 15 as having congenital esotropia, 15 as having primary
      acquired esotropia, 15 as having congenital exotropia, and 5 as having
      hypertropia. Visual acuity levels were measured using a Snellen E-chart. Fixation
      preference was evaluated and graded from 0 (free alternation) to 3 (strong
      uniocular fixation). At the end, we compared visual acuity and the grade of
      fixation preference. Amblyopia was defined as a difference of two or more Snellen
      lines between the two eyes. RESULTS: Sixty patients (75%) had strong uniocular
      fixation (grade 3). Of these patients, 50 (85%) had no amblyopia and only 10 had
      deep amblyopia. Ten patients (12.5%) had moderate fixation (grades 1 and 2). Of
      these patients, five (50%) had no amblyopia and five had moderate amblyopia. Ten
      patients (12.5%) had free alternation (grade 0). These patients had equal vision.
      CONCLUSION: Treatment of strabismic amblyopia on the basis that the sound eye
      will show strong fixation preference can be hazardous. Fixation preference could
      be a severe form of eye dominance, and better methods for testing visual acuity
      in preverbal children are required.

PMID- 17542441
TI  - Lymphangioma of the conjunctiva and nasal cavity in a child presenting with
      diffuse subconjunctival hemorrhage and nosebleeds.
AB  - A 4-year-old girl had extensive subconjunctival hemorrhage in the right eye. She
      had recurrent minor nosebleeds starting at 6 months. Visual acuity was 20/20.
      Anterior segment examination showed diffuse, blood-filled, multilobulated cystic
      channels in the conjunctiva. Bleeding resolved, leaving transparent cystic
      channels. Conjunctival lymphangioma can manifest as temporary subconjunctival
      lymphangioma.

PMID- 17542442
TI  - Bilateral exudative retinal detachment in a child with orbital pseudotumor.
AB  - We describe a 15-year-old girl who presented with bilateral exudative retinal
      detachment, a previously unreported complication, due to orbital pseudotumor. She
      initially responded to steroids, but subsequently became steroid dependent.
      Azathioprine was effective in controlling further relapses during follow-up of 22
      months.

PMID- 17542443
TI  - Morning glory anomaly with bilateral choroidal colobomas in a patient with
      Goldenhar's syndrome.
AB  - A child with Goldenhar's syndrome, bilateral choroidal colobomas, and a morning
      glory anomaly of the optic disk in one eye is described. Bilateral posterior
      segment anomalies associated with Goldenhar's syndrome are rare. An association
      between the morning glory anomaly and Goldenhar's syndrome has not been
      previously reported.

PMID- 17542444
TI  - Descemet's membrane breaks following forceps delivery.

PMID- 17542445
TI  - Integrating viral hepatitis prevention into public health programs serving people
      at high risk for infection: good public health.

PMID- 17542446
TI  - Texas statewide hepatitis C counseling and testing, 2000-2005.
AB  - In 1999, the Texas legislature funded a statewide hepatitis C education and
      prevention program. Hepatitis training was incorporated into training for all
      human immunodeficiency virus (HIV), sexually transmitted disease (STD), and
      substance abuse counselors. Hepatitis C virus (HCV) counseling and HCV-antibody
      (anti-HCV) testing services were integrated into 20 HIV/STD service provider
      programs. Hepatitis C counseling and testing became available in 2000. Through
      2005, 38,717 tests were administered, with 8,964 (23.2%) anti-HCV positive.
      Injection drug use was reported by 7,105 people (79.3%) who tested positive. In
      Texas, a state-initiated and almost entirely state-funded program supported
      statewide HCV counseling and anti-HCV testing among high-risk adults.

PMID- 17542447
TI  - Integrating viral hepatitis prevention services into an urban STD clinic: Denver,
      Colorado.
AB  - The Centers for Disease Control and Prevention recommends integrating viral
      hepatitis prevention services with services for adults evaluated for sexually
      transmitted diseases (STDs). The Denver Public Health STD clinic began hepatitis
      B vaccination in 1999, hepatitis C virus (HCV) antibody (anti-HCV) testing in
      2000, and hepatitis A vaccination in 2002. Rapid human immunodeficiency virus
      (HIV) testing began in late 2004. Hepatitis B vaccinations peaked in 2003 (31/100
      client visits) when a full-time nurse was hired to vaccinate and eligibility was
      expanded. The proportion of clients documented to have received their anti-HCV
      test results declined from an average of 71% in 2000-2003 to 22% in 2004-2005,
      coinciding with the introduction of rapid HIV testing. Viral hepatitis prevention
      services can be incorporated into a busy STD clinic if staff and resources are
      available. Rapid HIV testing may be associated with lower receipt of anti-HCV
      test results.

PMID- 17542448
TI  - Integrating viral hepatitis prevention into STD clinics in Illinois (excluding
      Chicago), 1999-2005.
AB  - Hepatitis B vaccination is recommended for all clients of sexually transmitted
      disease (STD) clinics. Hepatitis A vaccination and hepatitis C testing are
      recommended for STD clinic clients who report specific risks for those viruses.
      In 1999, the Illinois Department of Public Health began working with local health
      departments in Illinois (excluding Chicago) to introduce hepatitis B testing and
      vaccination in public STD clinics. Hepatitis A vaccination and hepatitis C
      counseling and testing were introduced in 2001. Illinois state funding has
      covered more than one-third of the costs of offering these integrated viral
      hepatitis services to STD clients. Hepatitis A and B vaccination and hepatitis C
      counseling and testing are now the standard of care in almost all (35 of 41)
      Illinois public STD clinics (excluding Chicago). In 2005, 29.4% of STD client
      visits included a hepatitis B vaccination. In public STD clinics in Illinois,
      hepatitis A and B vaccinations and hepatitis C counseling and testing have
      increased from essentially no activity in 1999 to substantial levels of service
      in 2005.

PMID- 17542449
TI  - Establishing a viral hepatitis prevention and control program: Florida's
      experience.
AB  - In 1999, the Florida State Legislature established and funded the statewide
      Hepatitis Prevention Program (HPP) to address growing concern about hepatitis C
      virus (HCV) and its potential public health burden. HPP supports county health
      departments' (CHDs') provision of viral hepatitis prevention services to at-risk
      adults through free hepatitis A and B vaccine in most CHDs and hepatitis
      serologic testing and statewide viral hepatitis-related education, consultation,
      and referral services. Some CHDs are directly funded by HPP. In 2001-2005, HPP
      support helped CHDs provide 59,228 hepatitis A and 74,039 hepatitis B
      vaccinations statewide. In 2005, HPP supported almost 17,000 hepatitis B and C
      tests. From January to June 2005, 1,603 positive HCV tests were reported, a 9.5%
      seropositivity rate. With $24 million from the Florida State Legislature through
      2006, HPP has helped CHDs statewide provide substantial viral hepatitis
      prevention services to at-risk adults.

PMID- 17542450
TI  - Does integrating viral hepatitis services into a public STD clinic attract
      injection drug users for care?
AB  - OBJECTIVE: Injection drug users (IDUs) are at high risk for multiple health
      problems, including human immunodeficiency virus (HIV), viral hepatitis, and
      sexually transmitted diseases (STDs), and are likely to have poor access to
      health care. To more effectively serve high-risk clients, experts recommend that
      programs accessed by such client populations offer integrated services. In 2000,
      the New York City Department of Health and Mental Hygiene integrated viral
      hepatitis services (vaccine and screening) into a publicly funded STD clinic. We
      evaluated integrated service delivery to high-risk IDUs at this clinic. METHODS:
      Hepatitis data were reviewed to identify clients who self-reported as IDUs. STD
      medical records of these clients were abstracted to ascertain primary reason for
      clinic visit, STD/HIV services received, and diagnoses made. RESULTS: Between May
      2000 and March 2004, 8,778 individuals received hepatitis services, of whom 3%
      (279/8,778) reported injection drug use. Nearly 60% (161/279) of IDUs reported
      availability of hepatitis services as the primary reason for the clinic visit. Of
      these 161 clients, 103 (64%) also received other services; 54% (55/103) had an
      STD exam (yielding 12 new STD diagnoses), and 59% (61/103) had HIV counseling and
      testing (yielding two new HIV cases). Of these 103 clients, 31 (30%) were
      referred to the clinic for hepatitis services from a drug treatment center, and
      77% (24/31) tested positive for the antibody to hepatitis C virus. CONCLUSIONS:
      Integrated hepatitis services appeared to attract IDUs to this STD clinic, where
      many also benefited from STD/HIV exams, testing, treatment, and referrals they
      may not have received otherwise.

PMID- 17542451
TI  - Expansion of adult hepatitis A and B vaccination in STD clinics and other
      settings in New York State.
AB  - Since 1995, the New York State (NYS) Adult Hepatitis Vaccination Program has
      promoted adult hepatitis B vaccination for those receiving sexually transmitted
      disease (STD) clinic services. An average of 6,333 doses was administered
      annually from 1995 to 1999. By 2000, only 15 of 57 county STD programs in NYS
      outside of New York City participated. From 2000 to 2005, efforts to enroll
      county health departments and others included outreach, provision of hepatitis A
      and B vaccine, materials and training, and new collaborations. All 57 counties
      now participate. From 2000 to 2005, the number of settings offering hepatitis
      vaccination increased from 57 to 119. Sites include STD clinics; jails; migrant,
      Indian health, and college health centers; and methadone clinics. More than
      125,000 doses of hepatitis A and B vaccine were administered from 1995 through
      2005, with annual increases up to a high of 21,025 doses in 2005. Intensive
      promotion expanded hepatitis vaccination to all county STD clinics and other
      settings where high-risk adults can be vaccinated.

PMID- 17542452
TI  - Hepatitis B vaccination in six STD clinics in the United States committed to
      integrating viral hepatitis prevention services.
AB  - OBJECTIVES: Hepatitis B vaccination is recommended for clients of sexually
      transmitted disease (STD) clinics. The Healthy People 2010 goal is for 90% of STD
      clinics to offer hepatitis B vaccine to all unprotected clients. This report
      describes hepatitis B vaccination trends in six STD clinics in the United States
      and discusses implications for policy and practice. METHODS: We conducted a
      retrospective study in six STD clinics to evaluate hepatitis B vaccination. We
      collected data on client visits and hepatitis B vaccinations for the period 1997
      2005. To compare clinics, we calculated vaccination rates per 100 client visits.
      We interviewed staff to explore factors associated with hepatitis B vaccination
      trends. RESULTS: STD clinic client visits ranged from 2,883 to 23,109 per year.
      The median rate of hepatitis B vaccination was 28 per 100 client visits.
      Vaccination rates declined in all six clinics in later years, which was
      associated with eligibility restrictions caused by fiscal problems and increasing
      levels of prior vaccination. The median rate of vaccine series completion was
      30%. Staff cited multiple provider- and client-level barriers to series
      completion. CONCLUSIONS: This study shows that STD clinics can implement
      hepatitis B vaccination and reach large numbers of high-risk adults. Adequate
      funding and vaccine supply are needed to implement current federal
      recommendations to offer hepatitis B vaccine to adults seen in STD clinics and to
      achieve the Healthy People 2010 objective.

PMID- 17542453
TI  - Viral hepatitis vaccination in an opioid treatment program: Hartford,
      Connecticut, 2002-2005.
AB  - Hartford Dispensary, a private, not-for-profit behavioral health care
      organization specializing in opioid treatment program services, serves more than
      4,200 clients per day in seven licensed facilities. In May 2002, the Dispensary
      began offering free combined hepatitis A and B vaccine for all eligible clients
      in two Hartford clinics. Initial eligibility criteria required a client to be
      hepatitis C antibody positive, hepatitis B virus (HBV) surface antigen (HBsAg)
      negative, not pregnant, and not have a contraindication due to a medical
      condition. From May 2002 through April 2005, 5,419 doses of combined vaccine were
      given. Of the 2,072 clients who received a first dose, 92% (1,914) received the
      second dose and 69% (1,433) completed the series. Long treatment duration,
      frequent client visits, availability of medical staff, and counseling support
      contributed to high rates of combined vaccine series completion in the two
      programs. Opioid treatment programs appear to be good settings in which to
      provide hepatitis vaccination for high-risk adults.

PMID- 17542454
TI  - Balancing the childhood immunization program with the urgent needs for adult
      hepatitis B immunization.

PMID- 17542455
TI  - The costs and impacts of testing for hepatitis C virus antibody in public STD
      clinics.
AB  - OBJECTIVES: To estimate the cost and cost-effectiveness of testing sexually
      transmitted disease (STD) clinic subgroups for antibodies to hepatitis C virus
      (HCV). METHODS: HCV counseling, testing, and referral (CTR) costs were estimated
      using data from two STD clinics and the literature, and are reported in 2006
      dollars. Effectiveness of HCV CTR was defined as the estimated percentage of
      clinic clients in subgroups targeted for HCV antibody (anti-HCV) testing who had
      a true positive test and returned for their test results. We estimated the cost
      per true positive injection drug user (IDU) who returned for anti-HCV test
      results and the cost-effectiveness of expanding HCV CTR to non-IDU subgroups.
      RESULTS: The estimated cost per true positive IDU who returned for test results
      was $54. The cost-effectiveness of expanding HCV CTR to non-IDU subgroups ranged
      from $179 to $2,986. Our estimates were most sensitive to variations in HCV
      prevalence, the cost of testing, and the rate of client return. CONCLUSIONS:
      Based on national data, testing IDUs in the STD clinic setting is highly cost
      effective. Some clinics may find that it is cost-effective to expand testing to
      non-IDU men older than 40 who report more than 100 lifetime sex partners. STD
      clinics can use study estimates to assess the feasibility and desirability of
      expanding HCV CTR beyond IDUs.

PMID- 17542456
TI  - Low prevalence of hepatitis C virus antibody in men who have sex with men who do
      not inject drugs.
AB  - OBJECTIVE: It is well documented that injection drug users (IDUs) have a high
      prevalence of antibodies to hepatitis C virus (HCV). Sexual transmission of HCV
      can occur, but studies have shown that men who have sex with men (MSM) without a
      history of injection drug use are not at increased risk for infection. Still,
      some health-care providers believe that all MSM should be routinely tested for
      HCV infection. To better understand the potential role of MSM in risk for HCV
      infection, we compared the prevalence of antibody to HCV (anti-HCV) in non-IDU
      MSM with that among other non-IDU men at sexually transmitted disease (STD)
      clinics and human immunodeficiency virus (HIV) counseling and testing sites in
      three cities. METHODS: During 1999-2003, public health STD clinics or HIV testing
      programs in Seattle, San Diego, and New York City offered counseling and testing
      for anti-HCV for varying periods to all clients. Sera were tested using enzyme
      immunoassays, and final results reported using either the signal-to-cutoff ratio
      or recombinant immunoblot assay results. Age, sex, and risk information were
      collected. Prevalence ratios and 95% confidence intervals were calculated.
      RESULTS: Anti-HCV prevalence among IDUs (men and women) was between 47% and 57%
      at each site, with an overall prevalence of 51% (451/887). Of 1,699 non-IDU MSM,
      26 (1.5%) tested anti-HCV positive, compared with 126 (3.6%) of 3,455 other non
      IDU men (prevalence ratio 0.42, 95% confidence interval 0.28, 0.64). CONCLUSION:
      The low prevalence of anti-HCV among non-IDU MSM in urban public health clinics
      does not support routine HCV testing of all MSM.

PMID- 17542457
TI  - HCV and HIV counseling and testing integration in California: an innovative
      approach to increase HIV counseling and testing rates.
AB  - OBJECTIVES: In California, injection drug users (IDUs) comprise the second
      leading risk group for human immunodeficiency virus (HIV) infection and the
      majority of hepatitis C virus (HCV) cases. Innovative disease screening and
      prevention activities are needed to improve disease surveillance and to guide
      appropriate public health responses. This study tested the hypothesis that
      offering HIV counseling and testing (C&T) concurrently with HCV C&T will increase
      HIV C&T rates among IDUs. METHODS: From February through June 2003, HIV and HCV
      C&T were integrated in five California local health jurisdictions. HIV C&T and
      disclosure rates among IDUs were monitored when HIV C&T was offered alone during
      a baseline phase and when offered with HCV C&T during an intervention phase
      RESULTS: Among IDUs, HIV C&T rates were significantly higher when HIV and HCV C&T
      were offered together (27.1%, 354/1,305) than when HIV C&T services were offered
      alone (8.4%, 138/1,645) (p<0.05). HIV disclosure rates increased from 54.3%
      (75/138) when only HIV test results were disclosed to 71.8% (254/354) when HIV
      test results were disclosed concurrently with HCV test results (p<0.05). HCV
      prevalence among IDUs tested ranged from 23% to 75% at the five project sites.
      Integrating HIV and HCV C&T increased overall C&T time required for staff and
      clients and increased stress among counselors due to the number of positive test
      results (HCV) given to clients. CONCLUSIONS: Study results suggest that
      integrating HIV and HCV C&T can increase disease screening rates among IDUs.
      Careful planning of integrated staff activities and schedules is recommended.

PMID- 17542458
TI  - Project ECHO: linking university specialists with rural and prison-based
      clinicians to improve care for people with chronic hepatitis C in New Mexico.
AB  - Project Extension for Community Healthcare Outcomes (Project ECHO) is a
      telemedicine and distance-learning program designed to improve access to quality
      health care for New Mexicans with hepatitis C. Project ECHO links health-care
      providers from rural clinics, the Indian Health Service, and prisons with
      specialists at the University of New Mexico. At weekly clinics, partners present
      and discuss patients with hepatitis C with specialists. Partners can receive
      continuing education credits for participating. Since June 2003, 173 hepatitis C
      clinics have been conducted with 1,843 case presentations. Partners have received
      390 hours of training and 2,997 hours of continuing education credits. And in
      2006, the State Legislature approved $1.5 million in annual funding for the
      project. Project ECHO has increased access to state-of-the art hepatitis C virus
      care for patients living in rural areas or prisons. Because of its success with
      hepatitis C, this project is being expanded to other chronic medical conditions.

PMID- 17542459
TI  - Managing chronic hepatitis C in primary-care settings: more than antiviral
      therapy.

PMID- 17542460
TI  - Promoting HCV treatment completion for prison inmates: New York State's hepatitis
      C continuity program.
AB  - This article describes the development of a statewide program providing
      continuity of hepatitis C virus (HCV) treatment to prisoners upon release to the
      community. We discussed length of stay as a barrier to treatment with key
      collaborators; developed protocols, a referral process, and forms; mobilized
      staff; recruited heath-care facilities to accept referrals; and provided short
      term access to HCV medications for inmates upon release. The Hepatitis C
      Continuity Program, including 70 prisons and 21 health-care facilities, is a
      resource for as many as 130 inmates eligible to start treatment annually. Health
      care facilities provide fairly convenient access to 87.1% of releasees, and 100%
      offer integrated HCV-human immunodeficiency virus/acquired immunodeficiency
      syndrome care. As of March 2006, 24 inmates had been enrolled. The program was
      replicated in the New York City Rikers Island jail. The program is operational
      statewide, referrals sometimes require priority attention, and data collection
      and other details are still being addressed.

PMID- 17542461
TI  - A community experience responding to hepatitis C.

PMID- 17542462
TI  - Advancing integration of HIV, STD, and viral hepatitis services: state
      perspectives.

PMID- 17542463
TI  - Integrating hepatitis services into substance abuse treatment programs: new
      initiatives from SAMHSA.

PMID- 17542464
TI  - CDC and progress toward integration of HIV, STD, and viral hepatitis prevention.

PMID- 17542465
TI  - In vivo estimates of the position of advanced bionics electrode arrays in the
      human cochlea.
AB  - OBJECTIVES: A new technique for determining the position of each electrode in the
      cochlea is described and applied to spiral computed tomography data from 15
      patients implanted with Advanced Bionics HiFocus I, Ij, or Helix arrays. METHODS:
      ANALYZE imaging software was used to register 3-dimensional image volumes from
      patients' preoperative and postoperative scans and from a single body donor whose
      unimplanted ears were scanned clinically, with micro computed tomography and with
      orthogonal-plane fluorescence optical sectioning (OPFOS) microscopy. By use of
      this registration, we compared the atlas of OPFOS images of soft tissue within
      the body donor's cochlea with the bone and fluid/ tissue boundary available in
      patient scan data to choose the midmodiolar axis position and judge the electrode
      position in the scala tympani or scala vestibuli, including the distance to the
      medial and lateral scalar walls. The angular rotation 0 degrees start point is a
      line joining the midmodiolar axis and the middle of the cochlear canal entry from
      the vestibule. RESULTS: The group mean array insertion depth was 477 degrees
      (range, 286 degrees to 655 degrees). The word scores were negatively correlated
      (r = -0.59; p = .028) with the number of electrodes in the scala vestibuli.
      CONCLUSIONS: Although the individual variability in all measures was large,
      repeated patterns of suboptimal electrode placement were observed across
      subjects, underscoring the applicability of this technique.

PMID- 17542466
TI  - Texas will run out of doctors to meet the demands of a growing and aging
      population over the next few decades.

PMID- 17542467
TI  - Frew v. Hawkins.

PMID- 17542468
TI  - Spoiling for a rematch.

PMID- 17542469
TI  - Going online.

PMID- 17542470
TI  - Diabetes risk factors and testing in a Texas family medicine clinic.
AB  - To examine whether the American Diabetes Association and the US Preventive
      Services Task Force risk factors are associated with testing for diabetes, we
      examined 300 medical records of patients aged 18 years or older who visited the
      Family Medicine Clinic at The University of Texas Medical Branch at Galveston.
      Demographic, medical history, and laboratory information were collected. A
      patient was considered tested if either a fasting or random plasma glucose was
      recorded. The frequency of glucose testing for those with one or more risk
      factors was 56%. Approximately 76% and 85% of those with hypertension and
      dyslipidemia were tested, respectively. Patients who were overweight, had
      hypertension, or had an annual examination were two to three times more likely (P
      < .05) to have a glucose test. Many patients who should be tested are not being
      tested. One way to improve the quality of care is to perform glucose testing on
      patients at high risk for diabetes and to obtain complete lipid profiles.

PMID- 17542471
TI  - Through education and awareness, school nurses can play an integral role in the
      identification and prevention of child abuse.

PMID- 17542472
TI  - Strategies for managing students with food allergies.

PMID- 17542473
TI  - Current clinical research on type 2 diabetes and its prevention in youth.
AB  - The SEARCH, TODAY, and HEALTHY studies, and NASN's SCOPE intervention, illustrate
      that collaboration between schools, school nurses, clinicians, students, and
      families can help treat and prevent diabetes and obesity in youth. Findings will
      help identify the prevalence of diabetes in young people, the best ways to treat
      youth with new-onset type 2 diabetes, and healthful practices that can reduce
      risk factors for cardiovascular disease. Findings about diabetes prevention in
      the school setting can guide school nurses and school leadership to incorporate
      effective changes into food and physical activity offerings to students. Finally,
      school nurses can communicate with primary care providers and provide culturally
      sensitive letters to parents and guardians regarding the BMI results for the
      child.

PMID- 17542474
TI  - National certification for school nurses: is it time for you to consider it?

PMID- 17542475
TI  - Be recognized: National School Nurse Day is May 9, 2007.

PMID- 17542476
TI  - Clinical challenges in recognizing, diagnosing, and treating anaphylaxis.

PMID- 17542477
TI  - Look for head lice.

PMID- 17542478
TI  - Chemodiversity of exudate flavonoids in seven tribes of Cichorioideae and
      Asteroideae (Asteraceae).
AB  - Members of several genera of Asteraceae, belonging to the tribes Mutisieae,
      Cardueae, Lactuceae (all subfamily Cichorioideae), and of Astereae, Senecioneae,
      Helenieae and Heliantheae (all subfamily Asteroideae) have been analyzed for
      chemodiversity of their exudate flavonoid profiles. The majority of structures
      found were flavones and flavonols, sometimes with 6- and/or 8-substitution, and
      with a varying degree of oxidation and methylation. Flavanones were observed in
      exudates of some genera, and, in some cases, also flavonol- and flavone
      glycosides were detected. This was mostly the case when exudates were poor both
      in yield and chemical complexity. Structurally diverse profiles are found
      particularly within Astereae and Heliantheae. The tribes in the subfamily
      Cichorioideae exhibited less complex flavonoid profiles. Current results are
      compared to literature data, and botanical information is included on the studied
      taxa.

PMID- 17542479
TI  - Antimicrobial isoflavonoids from Erythrina crista galli infected with Phomopsis
      sp.
AB  - The isoflavonoids coumestrol, genistein and daidzein have been isolated and
      identified by bioassay-guided fractionation from the acetone extract of Erythrina
      crista galli young twigs infected with Phomopsis sp. These compounds showed
      antimicrobial activity against Bacillus brevis (MIC values 16.3, 64.8 and 137.8
      microM, respectively). This is the first time that coumestrol, besides lutein and
      n-nonacosane, are reported in this species.

PMID- 17542480
TI  - Cytotoxic alpha-pyrones from Xylaria hypoxylon.
AB  - Two new alpha-pyrone derivatives, xylarone (1) and 8,9-dehydroxylarone (2)
      possessing cytotoxic activities, were isolated from the culture fluid of
      submerged cultures of the ascomycete Xylaria hypoxylon, strain A27-94. Their
      structures were elucidated by spectroscopic methods.

PMID- 17542481
TI  - Antibacterial activity of extract, fractions and four compounds extracted from
      Piper solmsianum C. DC. VAR. solmsianum (Piperaceae).
AB  - Piper solmsianum C. DC. var. solmsianum (Piperaceae) is a shrub commonly found in
      areas with wet tropical soils. Other Piper species have been used in folk
      medicine as antitumoral and antiseptic agents. We studied the crude methanolic
      extract, some organic fractions and compounds isolated from this plant for
      possible antimicrobial activity against Gram-positive and Gram-negative bacteria.
      The bioautographic assays disclosed three inhibition zones. The minimal
      inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) were
      determined showing excellent activity, particularly against the Gram-positive
      bacteria (Bacillus cereus, Staphylococcus aureus, Staphylococcus saprophyticus
      and Streptococcus agalactiae). It appears that the antimicrobial activity of
      Piper solmsianum is related mainly to the presence of conocarpan and eupomatenoid
      5 (neolignans). However another, as yet unidentified, active compound could also
      be extracted from the plant.

PMID- 17542482
TI  - Red Mexican grapefruit: a novel source for bioactive limonoids and their
      antioxidant activity.
AB  - Citrus limonoids have shown to inhibit the growth of cancer in colon, lung,
      mouth, stomach and breast in animal and cell culture studies. For the first time
      in the present study, an attempt has been made to isolate antioxidant fractions
      and five limonoids from red Mexican grapefruit seeds. Defatted seed powder was
      successively extracted with hexane, ethyl acetate (EtOAc), acetone, methanol
      (MeOH) and MeOH/water and the extracts were concentrated under vacuum. Radical
      scavenging activity of 1,1-diphenyl-2-picrylhydrazyl (DPPH) and total phenolic
      content were also measured for comparison with the antioxidant capacity in the
      phosphomolybdenum method for the above extracts. Acetone and MeOH extracts,
      respectively, showed the highest (85.7%) and lowest (53.3%) radical scavenging
      activity, at 500 ppm. The total phenolic contents were found to be highest in the
      acetone extract (15.94%) followed by the MeOH extract (5.92%), ethyl acetate
      extract (5.54%) and water extract (5.26%). Antioxidant capacity of the extracts
      as equivalents to ascorbic acid (micromol/g of the extract) was in the order,
      EtOAc extract > acetone extract > water extract > methanol extract. Furthermore,
      the EtOAC and acetone extracts were loaded onto silica gel columns to obtain four
      limonoid aglycons. MeOH fraction was loaded onto a dowex-50 and sepabeads resin
      column to obtain a limonoid glucoside. The purity of the isolated five compounds
      was analyzed by HPLC using a C18 column and UV detection at 210 nm. Finally, the
      structures of the compounds were identified as obacunone, nomilin, limonin,
      deacetylnomilin (DAN) and limonin-17-beta-D-glucopyranoside (LG) using 1H and 13C
      NMR studies.

PMID- 17542483
TI  - Antiproliferative activity of methylated analogues of E- and Z-resveratrol.
AB  - The stilbenoids E-resveratrol (E-3,5,4'-trihydroxystilbene, 1), E-3,5,4'
      trimethoxystilbene (2), E-3,4,4'-trimethoxystilbene (3) and E-3,4'-dimethoxy-5
      hydroxystilbene (4) were converted by photoisomerization to their corresponding Z
      isomers 5-8. Compounds 1-8 were subjected to antiproliferative activity bioassays
      towards a set of four different human cancer cell lines, namely DU-145 (androgen
      not responsive human prostate tumor), LNCaP (androgen responsive human prostate
      tumor), M-14 (human melanoma) and KB (human mouth epidermoid carcinoma). The
      methylated analogues of 1 are more active than the natural lead in the majority
      of bioassays. The most active compound was Z-3,5,4'-trimethoxystilbene (6), which
      showed against DU-145 and LNCaP cells GI50 values close to those of the
      anticancer drug vinorelbine; 6 resulted more active than its E-isomer 2 towards
      DU-145, LNCaP and especially KB cell lines. A number of methylated Z-isomers
      displayed a higher activity than their E-isomers, but E-resveratrol (1) was more
      active than Z-resveratrol (5) towards all the tested cell lines.

PMID- 17542484
TI  - Bioactive phenolic compounds from aerial parts of Plinia glomerata.
AB  - The present work describes the antinociceptive properties and chemical
      composition of the aerial parts of Plinia glomerata (Myrtaceae). Both of the
      extracts evaluated, acetonic and methanolic, showed potent antinociceptive
      action, when analyzed against acetic acid-induced abdominal constrictions in
      mice, with calculated ID50 (mg/kg, i. p.) values of 24.8 and 3.3, respectively.
      Through usual chromatographic techniques with an acetonic extract, the following
      compounds were obtained: 3,4,3'-trimethoxy flavellagic acid (1), 3,4,3'
      trimethoxy flavellagic acid 4'-O-glucoside (3) and quercitrin (4), which were
      identified based on spectroscopic data. Compounds 1 (ID50 = 3.9 mg/kg, i. p., or
      10.8 micromol/kg) and 3 (ID50 = 1.3 mg/kg or 2.5 micromol/kg) were notably more
      active than some well-known analgesic drugs used here for comparison.

PMID- 17542485
TI  - Antinociceptive effects of tetrahydrophthalimides and related compounds.
AB  - This paper describes the antinociceptive effects of tetrahydrophthalimides and
      related compounds in mice. Twenty compounds were obtained by the reaction of cis
      1,2,3,6-tetrahydrophthalic anhydride with appropriate amines, dehydration, and
      addition to the imidic double bond. They were analyzed in the writhing test at 10
      mg/kg given intraperitoneally. The most active compound 2-benzyl-5-morpholin-4-yl
      hexahydroisoindole-1,3-dione (19) was studied on formalin, capsaicin, glutamate
      and hot plate models. The antinociceptive activity demonstrated by some studied
      compounds is promising, and some of them were more active than acetylsalicylic
      acid and paracetamol used as reference drugs in writhing tests in mice. Compound
      19 was about 5-fold more potent than the reference drugs, being also effective by
      oral route and against the inflammatory response in the formalin test. The
      results suggest that compound 19 could be used as a model to obtain new and more
      potent antinociceptive agents. It exhibits an interesting antinociceptive
      profile, and does not interact with opioid systems.

PMID- 17542486
TI  - Inhibitory effects of monoterpenes on seed germination and seedling growth.
AB  - Monoterpenes, the chemical constituents of essential oils found in plants, are
      known biologically active compounds. The present study was conducted to
      investigate the inhibitory effects of 30 monoterpenes including monoterpene
      hydrocarbons and oxygenated monoterpenes on seed germination and seedling growth
      of Amaranthus retroflexus, Chenopodium album and Rumex crispus under laboratory
      conditions. The monoterpenes were applied at contents of 10 and 20 microl for
      liquid compounds and 10 and 20 microg for solid compounds. The results show that
      most of the monoterpenes significantly inhibited seed germination and seedling
      growth of the tested plants. Oxygenated monoterpenes including beta-citronellol,
      nerol and terpinen-4-ol completely inhibited seed germination and seedling growth
      of all tested plants. Their inhibitory effects were also stronger than that of
      the herbicide 2,4-D. In general, monoterpenes were less effective against seed
      germination and seedling growth of C. album as compared with R. crispus and A.
      retroflexus. Phytotoxic effects of monoterpene hydrocarbons were found to be
      lower than those of oxygenated monoterpenes. The alcohol derivatives of
      oxygenated monoterpenes were also found to be more phytotoxic as compared with
      their acetate derivatives. Based on the present results, it can be concluded that
      the oxygenated monoterpenes can be used as potential bio-herbicides.

PMID- 17542487
TI  - Protective effect of curcumin and chlorophyllin against DNA mutation induced by
      cyclophosphamide or benzo[a]pyrene.
AB  - The current study was carried out to evaluate the potency of curcumin and
      chlorophyllin as natural antioxidants to reduce the oxidative stress markers
      induced by cyclophosphamide (CP) and benzo[a]pyrene [B(a)P] which were used as
      free radical inducers. For this purpose, 126 male albino rats were used. The
      animals were assigned into 4 main groups: negative control group; oxidant-treated
      group (subdivided into two subgroups: cyclophosphamide-treated group and
      benzo[a]pyrene-treated group); curcumin-treated group; and chlorophyllin-treated
      group. Liver samples were collected after two days post the oxidant inoculation
      and at the end of the experimental period (10 weeks). These samples were examined
      for determination of liver microsomal malondialdehyde (MDA), DNA fragmentation,
      restriction fragment length polymorphism (RFLP) and 8-hydroxy deoxyguanosine (8
      OHdG) concentration. Both CP and B(a)P caused increments in DNA fragmentation
      percentages, liver microsomal MDA, concentration of 8-OHdG and induced point
      mutation. Treatment of rats with either curcumin or chlorophyllin revealed lower
      DNA fragmentation percentages, liver microsomal MDA concentration, concentration
      of 8-OHdG and prevented induction of mutations, i.e., reversed the oxidative
      stress induced by CP and B(a)P and proved that they were capable of protecting
      rats against the oxidative damage evoked by these oxidants.

PMID- 17542488
TI  - Alkaloids of Crinum x powellii "Album" (Amaryllidaceae) and their topoisomerase
      inhibitory activity.
AB  - The alkaloids lycorine, 1-O-acetyllycorine and ismine were isolated from the
      basic dichloromethane-soluble fraction of Crinum x powellii "Albu m" bulbs. The
      alkaloid structures were established by physical and spectroscopic analyses,
      including 1D NMR techniques and GC-MS analysis. The three alkaloids are reported
      for the first time for this hybrid. Additionally, the three alkaloids isolated
      were tested against a mechanism-based bioassay utilizing genetically engineered
      mutants of the yeast Saccharomyces cerevisiae strains RAD+, RAD52Y and RS321
      where lycorine was the only alkaloid that displayed moderate topoisomerase I
      inhibitory activity.

PMID- 17542489
TI  - Effects of salicylic acid on mushroom tyrosinase and B16 melanoma cells.
AB  - Salicylic acid slightly inhibited the oxidation of L-3,4-dihydroxyphenylalanine
      (L-DOPA) catalyzed by mushroom tyrosinase noncompetitively without being
      oxidized. In contrast, 4-hydroxybenzoic acid did not inhibit this enzymatic
      oxidation if a longer reaction time was observed, although it suppressed the
      initial rate of the oxidation to a certain extent. Neither acid showed noticeable
      effects on cultured murine B16-F10 melanoma cells except weak cytotoxicity.

PMID- 17542490
TI  - Nematicidal activity of 5-hydroxymethyl-2-furoic acid against plant-parasitic
      nematodes.
AB  - A nematicide, 5-hydroxymethyl-2-furoic acid (1), was isolated from cultures of
      the fungus Aspergillus sp. and its structure was identified by spectroscopic
      analysis. Compound 1 showed effective nematicidal activities against the pine
      wood nematode Bursaphelenchus xylophilus and the free-living nematode
      Caenorhabditis elegans without inhibitory activity against plant growth, but 1
      did not show any effective nematicidal activity against Pratylenchus penetrans.

PMID- 17542491
TI  - Effect of norflurazon on resorcinolic lipid metabolism in rye seedlings.
AB  - Norflurazon is a selective pyridazinone herbicide excessively employed in the
      control of many annual grasses and broad-leaved weeds. This chemical causes plant
      bleaching due to the inhibition of the carotenoid pigment biogenesis as well as
      induces irreparable changes to chloroplasts, which are considered the organelles
      where the biosynthesis of resorcinolic lipids takes place. Resorcinolic lipids, a
      group of phenolic compounds, constitute not only an essential part of the plant
      antifungal defense system, but also are an important component of the human
      cereal diet. The aim of this study was to investigate the effect of norflurazon
      on the biosynthesis of resorcinolic lipids in 5-day-old rye plants (Secale
      cereale L.) that were grown at three different temperatures under light or dark
      conditions. At all tested temperatures, norflurazon decreased the fresh biomass
      of light-grown rye seedlings and increased the weight of plants grown in
      darkness. Compared with respective controls, this herbicide caused an increase in
      total content of alkylresorcinols in both green and etiolated plants with the
      exception of dark-grown norflurazon-treated rye at 29 degrees C. The general
      level of saturated homologues was markedly decreased by norflurazon in all
      etiolated plants and in light-grown seedlings at 15 degrees C. Independent of
      thermal and light conditions, in all norflurazon-treated samples two
      alkylresorcinol derivatives predominated: 1,3-dihydroxy-5-n-heptadecylbenzene and
      1,3-dihydroxy-5-n-nonadecylbenzene. Thus, our results suggest that norflurazon
      affected the metabolism of alkylresorcinols in rye seedlings and its action was
      dependent on external stimuli.

PMID- 17542492
TI  - UV-B effect on constituents of Azolla caroliniana.
AB  - Changes in growth and ultrastructure of Azolla caroliniana in response to
      elevated UV-B radiation were investigated. Exposure of plants to UV-B radiation
      for 1, 8, 16, 24 and 48 h exhibited a significant decrease in biomass and
      relative growth rate. This decrease resulted in an increase in doubling time over
      the control. Also, Chl a and b contents were significantly decreased especially
      after 16 h. The reduction was accompanied by a decrease in 5-aminolaevulinic acid
      content (precursor of chlorophyll). On the other hand, contents of carotenoid and
      UV-absorbing phenolic compounds (flavonoids and anthocyanins) were increased.

PMID- 17542493
TI  - Effect of membrane fluidity on photosynthetic oxygen production reactions.
AB  - The effect of changes of membrane fluidity on the oxygen evolving capability of
      isolated thylakoids was investigated. Alteration of the lipid phase fluidity was
      achieved by incorporation of the plant sterol stigmasterol. Incorporation of
      stigmasterol in the lipid bilayer of thylakoid membranes results in rigidization
      of the hydrophobic phase of thylakoid membranes and decreases the degree of
      packing of the lipid head groups. These changes of lipid order are accompanied by
      a reduction of oxygen evolution, measured with 1,4-benzoquinone as an electron
      acceptor, and by a more pronounced inhibition of PSI-mediated electron transport.
      By analysis of the parameters of oxygen flash yields and oxygen burst under
      continuous illumination it was shown that after treatment with stigmasterol: 1.)
      the number of active oxygen-evolving centres decreased; 2.) the remaining active
      oxygen-evolving centres were not affected in respect to the oscillation pattern;
      3.) the contribution of the slow oxygen-evolving centres in oxygen burst yield
      was increased. The effect of stigmasterol was compared with the well-studied
      effect of cholesterol. Results were discussed in terms of determining the role of
      lipid order for the organization and functioning of the photosynthetic machinery.

PMID- 17542494
TI  - Biosorption of binary mixtures of copper and cobalt by Penicillium
      brevicompactum.
AB  - This work reports on a study of the biosorption of copper and cobalt, both singly
      and in combination (in equimolar concentrations), by the resting cells of
      Penicillium brevicompactum. Equilibrium batch sorption studies were carried out
      at 30 degrees C and pH 5.0 for a contact time of 1 hour to guarantee that
      equilibrium was reached. The equilibrium data were analyzed using the Langmuir
      and Freundlich isotherms. The adsorption of binary mixtures of heavy metal
      solutions on the fungal biomass was found to be of competitive type where the
      adsorption capacity for any single metal decreased in the presence of the other.
      The cobalt ions showed a higher affinity for Penicillium brevicompactum than the
      copper ions.

PMID- 17542495
TI  - Multiple effects of cadmium on the photosynthetic apparatus of Avicennia
      germinans L. as probed by OJIP chlorophyll fluorescence measurements.
AB  - The toxic effects of cadmium on the photosynthetic apparatus of Avicennia
      germinans were evaluated by means of the chlorophyll fluorescence transient O-J-I
      P. The chlorophyll fluorescence transients were recorded in vivo with high time
      resolution and analyzed according to the OJIP-test that can quantify the
      performance of photosystem II. Cadmium-treated plants showed a decrease in yield
      for primary photochemistry, TR0/ABS. The performance index of photosystem II
      (PSII), PI(ABS), decreased due to cadmium treatment. This performance index is
      the combination of the indexes of three independent parameters: (1) total number
      of active reaction centers per absorption (RC/ABS), (2) yield of primary
      photochemistry (TR0/ABS), and (3) efficiency with which a trapped exciton can
      move an electron into the electron transport chain (ET0/TR0). Additionally, the
      F0/Fv registered the highest sensitivity to the metal, thus indicating that the
      water-splitting apparatus of the oxidizing side of PSII is the primary site of
      action of cadmium. In summary, cadmium affects several targets of photosystem II.
      More specifically the main targets of cadmium, according to the OJIP-test, can be
      listed as a decrease in the number of active reaction centers and damage to the
      activity of the water-splitting complex.

PMID- 17542496
TI  - L-amino acid oxidases with specificity for basic L-amino acids in cyanobacteria.
AB  - The two closely related fresh water cyanobacteria Synechococcus elongatus PCC
      6301 and Synechococcus elongatus PCC 7942 have previously been shown to
      constitutively express a FAD-containing L-amino acid oxidase with high
      specificity for basic L-amino acids (L-arginine being the best substrate). In
      this paper we show that such an enzyme is also present in the fresh water
      cyanobacterium Synechococcus cedrorum PCC 6908. In addition, an improved
      evaluation of the nucleotide/amino acid sequence of the L-amino acid oxidase of
      Synechococcus elongatus PCC 6301 (encoded by the aoxA gene) with respect to the
      FAD-binding site and a translocation pathway signal sequence will be given.
      Moreover, the genome sequences of 24 cyanobacteria will be evaluated for the
      occurrence of an aoxA-similar gene. In the evaluated cyanobacteria 15 genes
      encoding an L-amino acid oxidase-similar protein will be found.

PMID- 17542497
TI  - Isolation and characterization of a novel n-alkane-degrading strain,
      Acinetobacter haemolyticus AR-46.
AB  - Strain AR-46, isolated and identified as Acinetobacter haemolyticus,
      evolutionally distant from the known hydrocarbon-degrading Acinetobacter spp.,
      proved to have excellent long-chain n-alkane-degrading ability. This is the first
      detailed report on an n-alkane-utilizing strain belonging to this species. The
      preferred substrate is n-hexadecane, with an optimal temperature of 37 degrees C
      under aerobic conditions. Five complete and two partial open reading frames were
      sequenced and correlated with the early steps of monoterminal oxidation-initiated
      n-alkane mineralization. The encoded protein sequences and the arrangement of
      these genes displayed high similarity to those found in Acinetobacter sp. M-1,
      but AR-46 seemed to have only one alkane hydroxylase gene, with a completely
      different induction profile. Unique behaviour was also observed in n-alkane
      bioavailability. Substrate uptake occurred through the hydrophobic surface of n
      alkane droplet-adhered cells possessing long, thick fimbriae, which were presumed
      to play a major role in n-alkane solubilization. A majority of the cells was in
      detached form, with thick, but short fimbriae. These free cells were permanently
      hydrophilic, unlike the cells of other Acinetobacter strains.

PMID- 17542498
TI  - A new 1-deoxy-D-xylulose 5-phosphate reductoisomerase gene encoding the committed
      step enzyme in the MEP pathway from Rauvolfia verticillata.
AB  - 1-Deoxy-D-xylulose 5-phosphate (DXP) reductoisomerase (DXR; EC 1.1.1.267)
      catalyzes a committed step of the methylerythritol phosphate (MEP) pathway for
      the biosynthesis of pharmaceutical terpenoid indole alkaloid (TIA) precursors.
      The full-length cDNA sequence was cloned and characterized from a TIA-producing
      species, Rauvolfia verticillata, using rapid amplification of cDNA ends (RACE)
      technique. The new cDNA was named as RvDXR and submitted to GenBank to be
      assigned with an accession number (DQ779286). The full-length cDNA of RvDXR was
      1804 bp containing a 1425 bp open reading frame (ORF) encoding a polypeptide of
      474 amino acids with a calculated molecular mass of 51.3 kDa and an isoelectric
      point of 5.88. Comparative and bioinformatic analyses revealed that RvDXR showed
      extensive homology with DXRs from other plant species and contained a conserved
      transit peptide for plastids, an extended Pro-rich region and a highly conserved
      NADPH-binding motif in its N-terminal region owned by all plant DXRs. The
      phylogenetic analysis revealed that DXRs had two groups including a plant and
      bacterial group; RvDXR belonged to angiosperm DXRs that were obtained from
      Synechocystis through gene transfer according to the phylogenetic analysis. The
      structural modeling of RvDXR showed that RvDXR had the typical V-shaped structure
      of DXR proteins. The tissue expression pattern analysis indicated that RvDXR
      expressed in all tissues including roots, stems, leaves, fruits and followers but
      at different levels. The lowest transcription level was observed in followers and
      the highest transcription was found in fruits of R. verticillata; the
      transcription level of RvDXR was a little higher in roots and stems than in
      leaves. The cloning and characterization of RvDXR will be helpful to understand
      more about the role of DXR involved in R. verticillata TIA biosynthesis at the
      molecular level and provides a candidate gene for metabolic engineering of the
      TIAs pathway in R. verticillata.

PMID- 17542499
TI  - In vitro inhibition of cholinesterases by carbamates--a kinetic study.
AB  - Kinetics and mechanism of in vitro hydrolyses of acetylcholine and
      acetylthiocholine by carbamates were studied in a batch reactor at 25 degrees C,
      pH 8, and ionic strength of 0.11 M. Every hydrolysis was monitored by 3-4
      independent methods. All studied hydrolyses can be described by the model of
      competitive inhibition with an irreversible step (k3). A table of obtained
      average values of rate constants and discussion of the resultes are given.

PMID- 17542500
TI  - Inhibition of cholinesterase by dialkylcarbamates.
AB  - The pI50 index and separation coefficients of chosen 3-N,N-diethylaminophenyl
      N',N'-dialkylcarbamates were determined. Index pL50 (pI50 = negative logarithm of
      molar concentration of inhibitor inhibiting the enzyme activity by 50%) describes
      the effectiveness of the inhibitor. The rate of ability of the inhibitor to pass
      the blood-brain barrier is usually described by the separation coefficient in a
      system n-octanol/water (K(ow)). Obtained results were compared with pL50 and
      K(ow) of Exelon, the commercially used drug against the Alzheimer's disease.

PMID- 17542501
TI  - Neurophysiological detection of iatrogenic C-5 nerve deficit during anterior
      cervical spinal surgery.
AB  - OBJECT: The incidence of postoperative C-5 spinal nerve root palsy following
      decompressive cervical spinal surgery has been reported to be as high as 12% for
      anterior procedures and 30% for posterior procedures. The present study was
      conducted to document the prevalence of iatrogenic C-5 nerve root deficit during
      anterior cervical spinal surgery, as well as to evaluate the sensitivity and
      specificity of intraoperative transcranial electrical stimulation (TES)-induced
      motor evoked potentials (MEPs) and spontaneous electromyographic (EMG) activity
      for identifying evolving C-5 nerve root impairment. METHODS: The authors
      conducted a retrospective study of 238 consecutive anterior cervical spinal
      procedures performed by a single surgeon at Christiana Care Hospital within a 48
      month period. Techniques used to monitor spinal nerve root function included TES
      induced MEPs and spontaneous EMG activity from deltoid, biceps, triceps, wrist
      extensor, and hand intrinsic muscles innervated by the C5-T1 spinal nerve roots.
      Spinal cord function was monitored by recording TES-induced MEPs from upper- and
      lower-extremity muscles as well as somatosensory evoked potentials from
      stimulation of the ulnar and posterior tibial nerves. CONCLUSIONS: Transcranial
      electrical stimulation-induced MEPs and spontaneous EMG activity offer
      complementary information about evolving iatrogenic C-5 spinal nerve root
      impairment during anterior cervical spinal surgery. The TES-induced MEPs provide
      prognostic information and show increased sensitivity to C-5 deficit compared
      with spontaneous EMG activity alone. Monitoring of spinal nerve root function
      using only EMG activity carries a risk of false-negative findings; without timely
      warning of impending neurological impairment, timely intervention to prevent
      permanent deficit cannot occur.

PMID- 17542502
TI  - Postlaminoplasty cervical range of motion: early results.
AB  - OBJECT: The authors studied cervical range of motion (ROM) before and after
      cervical laminoplasty to determine factors associated with cervical ROM in
      patients with cervical myelopathy. METHODS: Between July 2003 and August 2005, 20
      patients underwent a modified Hirabayashi-type unilateral open-door laminoplasty
      to treat multilevel cervical spondylosis or ossification of the posterior
      longitudinal ligament (OPLL). Clinically, the authors assessed Japanese
      Orthopaedic Association (JOA) score, duration of symptoms, disease entity, and
      the age and sex of patients to ascertain the relation of these factors to ROM
      before and after cervical laminoplasty. Intraoperative findings such as ligament
      detachment from the C-2 spinous process and cervicothoracic junction involvement
      were noted. Radiological and imaging findings such as the length of the lesion,
      cervical axial canal area, anteroposterior (AP) diameter of the cervical canal,
      angle of the opened lamina after surgery, cervical sagittal angles, cervical
      curvature index (CCI), and signal change of the cord on magnetic resonance
      imaging were evaluated. The mean follow-up period was 19.45 months (range 13-38
      months). The preoperative average ROM in 18 patients (after excluding two
      patients with trauma) was 36.73 +/- 15.73 degrees; postoperatively it was 25.24
      +/- 16.06 degrees. Thus, ROM decreased by 9.64 +/- 10.09 degrees (31.80%) after
      surgery (p = 0.002), reflecting the mean in the same 18 patients. Preoperative
      ROM was related to the age of patients, CCI, preoperative JOA score, and AP
      diameter of the cervical canal. In cases of OPLL the ROM was lower than that in
      cases of spondylosis. Postoperative cervical ROM was related to preoperative ROM,
      postoperative AP diameter of the cervical canal, laminar angle, patient age, and
      follow-up duration. None of the studied parameters, however, correlated with a
      decreased cervical ROM. CONCLUSIONS: Cervical ROM was reduced after cervical
      laminoplasty. Postlaminoplasty cervical ROM had a positive correlation with
      extended motion; however, gradually it became reduced. In this study, no
      correlative factor was associated with a reduction in cervical ROM. Further study
      is also needed.

PMID- 17542503
TI  - Stress-shielding compared with load-sharing anterior cervical plate fixation: a
      clinical and radiographic prospective analysis of 50 patients.
AB  - OBJECT: In a prospective analysis the authors evaluated the clinical and
      radiographic outcome of 50 consecutive patients who underwent anterior cervical
      discectomy and fusion and fixation in which either a stress-shielding or a load
      sharing plate (Orion and Premier, respectively) was placed. Data obtained in the
      two cohorts were analyzed to determine whether clinical or radiographic
      differences would emerge. METHODS: All patients underwent either one- or two
      level fusion in which freeze-dried allogenic tricortical iliac crest bone graft
      was used. In the first cohort of 25 patients entered into the study, fixation was
      achieved using a stress-shielding anterior cervical plate (ACP) system, whereas
      in the second cohort of 25 patients a load-sharing plate system was employed.
      Patients were evaluated during a follow-up period that ranged from 12 to 35
      months. Outcome was determined using a standard questionnaire by which the
      authors gauged the level of pain, disability, and satisfaction following surgery.
      The success of surgical fusion and the magnitude of the translation were
      determined by radiographic evaluation. There was no statistically significant
      difference between the two cohorts with respect to age, sex, smoking rate, and
      postoperative complications. With regard to pain and functionality, there was a
      significant difference (p < 0.05) in favor of the load-sharing system. The fusion
      rates with the load-sharing and stress-shielding systems were 96 and 92%,
      respectively, and this difference was not significant. There was no significant
      difference between the two cohorts with regard to overall satisfaction. The
      magnitude of vertical translation was significantly greater in the stress
      shielding ACP group (p < 0.05) for treatment at one level but not at two.
      Clinical and radiographic data were available in all patients. CONCLUSIONS: Load
      sharing ACP systems exhibited superior clinical results compared with stress
      shielding ACPs in this series of patients. The symptomatic pseudarthrosis rate
      was lower in the load-sharing ACP-treated patients, although this was not
      statistically significant.

PMID- 17542504
TI  - Surgical management of chordomas of the cervical spine.
AB  - OBJECT: Chordomas of the cervical spine are rare tumors. Although en bloc
      resection has proven to be the ideal procedure in other areas, there is
      controversy regarding this approach in the cervical spine. The goal in this study
      was to determine whether piecemeal tumor resection was efficient in the
      management of chordomas that arise in this location. METHODS: The authors
      retrospectively reviewed all 74 cases of chordoma treated by their group. Seven
      patients with isolated cervical chordomas who were treated between October 1992
      and January 2006 were identified. There were four male and three female patients,
      whose ages ranged from 6 to 61 years (mean 34.4 years). Follow-up duration ranged
      from 7 to 169 months (median 23 months). All cases were managed using a
      retrocarotid approach with mobilization of the vertebral artery. When the tumor
      could not be completely resected via the initial anterior approach, a subsequent
      posterior resection was performed. Tumor resection was intralesional in all
      cases, and gross-total tumor resection was achieved in six cases. One patient
      required a second resection 4 months later. In all cases, a posterior
      stabilization procedure was performed. Five patients underwent anterior fusion
      (three with fibular allograft and two with iliac crest), whereas two underwent
      occipitocervical fusion. In two patients with dedifferentiated chordoma
      metastasis developed, and one of them died 7 months later. The other patient with
      metastasis died suddenly at home 26 months postsurgery, presumably from
      aspiration. At the time of this submission, there were no signs of recurrence in
      five patients. CONCLUSIONS: The authors believe that, in most cases, en bloc
      resection of cervical chordoma is not feasible. This is due to the tendency of
      chordomas to involve multiple compartments at the time of diagnosis. In the
      authors' experience, intralesional radical resection remains an effective
      surgical approach to this disease entity.

PMID- 17542505
TI  - Negative-pressure wound therapy in the treatment of complex postoperative spinal
      wound infections: complications and lessons learned using vacuum-assisted
      closure.
AB  - OBJECT: Deep infections of the spine are a significant cause of morbidity and
      death. Such infections complicate 0.7 to 11.9% of spinal procedures. Management
      includes intravenous antibiotic therapy, debridement and irrigation with primary
      closure, placement of drains, use of irrigation systems, and/or healing through
      secondary intention with wound packing. Vacuum-assisted closure (VAC) is a new
      alternative for treatment of patients with complex postoperative spinal
      infections. The aim of this study was to investigate the safety of this treatment
      method in this patient population. METHODS: The authors reviewed the charts of 16
      consecutive patients treated with negative-pressure wound therapy at their
      institution between 2002 and 2006. All had deep infections of the spine and were
      treated with surgical debridement and placement of VAC dressings. All infections
      were postoperative. Members of the infectious disease service were involved in
      the care of all patients, and all patients received intravenous antibiotic
      therapy. The authors reviewed operative notes, discharge summaries, and notes
      from follow-up visits and assessed outcome on the basis of the same records.
      Three patients were lost to follow up, leaving a group of 13 with follow up of at
      least 90 days. Two patients experienced bleeding complications related to the
      continuous negative pressure of the VAC device. In two cases, the infections
      persisted and required reoperation. In one case, a skin graft was required
      because of nonhealing granulation tissue. One of the patients with bleeding
      complications died as a result of delayed complications related to intraoperative
      blood loss, blood loss via the VAC system, and refusal of a blood transfusion on
      religious grounds. CONCLUSIONS: Negative-pressure wound therapy has been employed
      as a treatment strategy for patients with complex postoperative spinal
      infections, but little is known of the complications associated with VAC in the
      spinal surgery patient population. Serious complications, including death, may be
      associated with use of the VAC system.

PMID- 17542506
TI  - Bone marrow stromal cells promoting corticospinal axon growth through the release
      of humoral factors in organotypic cocultures in neonatal rats.
AB  - OBJECT: The transplantation of bone marrow stromal cells (BMSCs) is considered to
      be an alternative treatment to promote central nervous system regeneration, but
      the precise mechanisms of this regeneration after transplantation of BMSCs have
      not been clarified. In the present study, the authors assessed the effects of
      BMSC transplantation on corticospinal axon growth quantitatively, and they
      analyzed the mechanism of central nervous system regeneration in the injured and
      BMSC-treated spinal cord using the organotypic coculture system. METHODS: Bone
      marrow stromal cells derived from green fluorescent protein-expressing transgenic
      Sprague-Dawley rats were transplanted to the organotypic coculture system in
      which brain cortex and spinal cord specimens obtained in neonatal Sprague-Dawley
      rats were used. The axon growth from the cortex to the spinal cord was assessed
      quantitatively, using anterograde tracing with 1,1 '-ioctadecyl-3,3,3',3'
      tetramethylindocarbocyanine perchlorate. To identify the differentiation of
      transplanted BMSCs, immunohistochemical examinations were performed. In addition,
      BMSCs were analyzed using reverse transcriptase polymerase chain reaction (RT
      PCR) for mRNA expression of the growth factors. The transplantation of BMSCs
      beneath the membrane, where the transplanted cells did not come into direct
      contact with the cultured tissue, promoted corticospinal axon growth to the same
      extent as transplantation of BMSCs on the tissues. The RT-PCR showed that the
      transplanted BMSCs expressed the mRNA of brain-derived neurotrophic factor (BDNF)
      and vascular endothelial growth factor (VEGF). Con CONCLUSIONS: ese findings
      strongly suggest that humoral factors expressed by BMSCs, including BDNF and
      VEGF, participate in regeneration of the central nervous system after
      transplantation of these cells.

PMID- 17542507
TI  - Antihyperalgesic effects of vanilloid-1 and bradykinin-1 receptor antagonists
      following spinal cord injury in rats.
AB  - OBJECT: The authors previously discovered that genes for the bradykinin-1 (B1)
      receptor and the transient receptor potential vanilloid subtype 1 (TRPV1) were
      overexpressed in animals exhibiting thermal hyperalgesia (TH) following spinal
      cord injury (SCI). They now report the effect of TRPV1 (AMG9810) and B1 (Lys-[Des
      Arg9,Leu8]-bradykinin) antagonists on TH in animals following SCI. METHODS: The
      rats were subjected to contusion SCI and then divided into groups in which TH did
      or did not develop. The animals from both groups were given either AMG9810, Lys
      (Des-Arg9,Leu8)-bradykinin, or the drug-specific vehicle (control groups).
      Animals were tested for TH preinjury and at regular intervals after SCI by using
      the hindlimb withdrawal latency test. CONCLUSIONS: The administration of AMG9810
      likely improves TH as a result of a generalized analgesic effect, whereas the
      effect of Lys-(Des-Arg9,Leu8)-bradykinin appears more specific to the reversal of
      TH. This information has potential usefulness in the development of treatment
      strategies for post-SCI neuropathic pain.

PMID- 17542508
TI  - The expression of Fas ligand on normal and stabbed-disc cells in a rabbit model
      of intervertebral disc degeneration: a possible pathogenesis.
AB  - OBJECT: The nucleus pulposus has been reported to be an immunologically
      privileged site. The expression of Fas ligand (FasL) on normal and herniated
      lumbar disc cells has been reported. The relationship between a physiological
      barrier and the role of FasL has not yet been addressed. To clarify this
      relationship and to investigate a possible pathogenesis of intervertebral disc
      degeneration (IDD), the expression of Fas and FasL (a mean apoptosis index) on
      normal and stabbed-disc cells was examined in a rabbit model of IDD. METHODS:
      Using defined needle gauges and depths, the anular puncture model of IDD was
      established in rabbits. The normal and stabbed discs were harvested at 3, 6, and
      10 weeks after surgery. Immunohistochemical staining of these discs for Fas and
      FasL was performed using standard procedures. The mean apoptosis indices of the
      disc cells were determined using flow cytometry analysis. The nucleus pulposus
      cells from the normal discs exhibited relatively weak immunopositivity, whereas
      the nucleus pulposus cells from the stabbed discs exhibited strong
      immunopositivity. There was a significant difference (p < 0.001) in the
      percentage of FasL-positive nucleus pulposus cells between the normal discs and
      the stabbed discs. The mean apoptosis indices of the stabbed-disc cells at 3, 6,
      and 10 weeks poststab were significantly higher than those in normal disc cells
      (p < 0.001, 0.002, and 0.006, respectively). There was a significant correlation
      between the degree of FasL-positive expression and the degree of Fas-positive
      expression of the nucleus pulposus cells poststab (r = 0.571, p = 0.0036).
      CONCLUSIONS: These observations indicate that the nucleus pulposus is an
      immunologically privileged site. This immunological privilege is maintained by
      FasL and the physiological barrier together. When the physiological barrier was
      damaged (by stabbing the disc), the role of FasL changed, and FasL was
      coexpressed with Fas to induce apoptosis of disc cells. These results indicate
      that an autoimmune reaction may be a possible pathogenesis of IDD.

PMID- 17542509
TI  - Evaluation of hydroxyapatite ceramic vertebral spacers with different porosities
      and their binding capability to the vertebral body: an experimental study in
      sheep.
AB  - OBJECT: The aim of this study was to evaluate the degree of bone ingrowth and
      bonding stiffness at the surface of hydroxyapatite ceramic (HAC) spacers with
      different porosities in an animal model and to discuss the ideal porous
      characteristics of these spacers for anterior spinal reconstruction. METHODS:
      Twenty-one adult sheep (age 1-2 years, mean weight 70 kg) were used in this
      experiment. Surgery consisted of anterior lumbar interbody fusion at L2-3 and L4
      5, insertion of an HAC spacer (10 x 13 x 24 mm) with three different porosities
      (0, 3, and 15%), and single-rod anterior instrumentation. At 4 and 6 months
      postoperatively, the lumbar spines were harvested. Bonding conditions at the bone
      HAC spacer interface were evaluated using neuroimages and biomechanically. A
      histological evaluation was also conducted to examine the state of bone ingrowth
      at the surface of the HAC spacer. Biomechanical testing showed that the bonding
      strength of HAC at 6 months postoperatively was 0.047 MPa in 0% porosity spacers,
      0.39 MPa in 3%, and 0.49 MPa in 15% porosity spacers. The histological study
      showed that there was a soft-tissue layer at the surface of the HAC spacer with
      0% porosity. Direct bonding was observed between bone and spacers with 3 or 15%
      porosity. Micro-computed tomography scans showed direct bonding between the bone
      and HAC with 3 or 15% porosity. No direct bonding was observed in HAC with 0%
      porosity. CONCLUSIONS: Dense (0%) HAC anterior vertebral spacers did not achieve
      direct bonding to the bone in the sheep model. The HAC vertebral spacers with 3
      or 15% porosity showed proof of direct bonding to the bone at 6 months
      postoperatively. The higher porosity HAC spacer showed better bonding stiffness
      to the bone.

PMID- 17542510
TI  - Intramedullary leiomyolipoma of the thoracic spine. Case report.
AB  - The authors report a rare case of spinal intramedullary leiomyolipoma. The
      histological characteristics and location of the neoplasm are unique, and the
      presentation, surgical management, and pathological characteristics of the lesion
      are discussed.

PMID- 17542511
TI  - Primary paraspinal leiomyosarcoma invading the cervical spinal canal successfully
      treated with surgery, radiotherapy, and chemotherapy. Case report.
AB  - A primary paraspinal leiomyosarcoma invading the spine is an exceedingly rare
      neoplasm that may clinically mimic a schwannoma. The authors report a case
      involving a 45-year-old man with a primary leiomyosarcoma of the cervical
      paraspinal musculature that invaded the spinal canal at C1-2 and subsequently
      metastasized to the lungs and pancreas. Aggressive treatment consisting of
      resection of the primary tumor, adjunctive radiation therapy and chemotherapy,
      and surgical debulking of metastatic disease resulted in local tumor control at
      the primary site and long-term survival of the patient.

PMID- 17542512
TI  - Expression of O6-methylguanine-deoxyribose nucleic acid methyltransferase and
      temozolomide response in a patient with a malignant spinal cord astrocytoma. Case
      report.
AB  - The authors report the case of a 28-year-old woman with a high-grade spinal cord
      astrocytoma. Treatment using surgery, radiation, and temozolomide (TMZ) led to
      functional recovery and regression of the residual tumor as demonstrated on
      serial magnetic resonance images. Genetic testing revealed that this tumor did
      not express the DNA repair enzyme O6-methylguanine-DNA methyltransferase (MGMT).
      This is the first report in the literature correlating MGMT expression with the
      clinical response of a high-grade spinal cord astrocytoma treated using TMZ.

PMID- 17542513
TI  - Malignant transformation of spinal meningeal melanocytoma. Case report and review
      of the literature.
AB  - Meningeal melanocytomas are rare tumors and malignant transformation of these
      lesions is even rarer. The authors report on a case of a 57-year-old man who
      presented with a melanocytoma located at the L5-S1 level. After gross-total
      resection of the tumor, it recurred 1 year later as a malignant melanoma. In
      addition, multiple subcutaneous metastases were found at that time. The patient
      was treated with radiation therapy (5000 cGy). Five months later metastases in
      the liver and the left ninth rib were discovered. The pertinent literature is
      reviewed and disease criteria are presented to distinguish meningeal melanocytoma
      from malignant melanoma and from meningiomas or schwannomas containing melanotic
      pigment. Patients and investigators should be cautioned that a meningeal
      melanocytoma may recur and transform into a malignant melanoma.

PMID- 17542514
TI  - Castleman disease of the spine mimicking a nerve sheath tumor. Case report.
AB  - Castleman disease is a rare lymphoproliferative disease of unknown cause. In most
      cases, afflicted patients present with a mediastinal mass although the disease
      may manifest in numerous other sites, including intracranially and rarely
      intraspinally. The authors report on the case of a 19-year-old woman who
      presented with a large paraspinal mass emanating from the T7-8 neural foramen.
      The morphological and signal characteristics revealed on magnetic resonance
      imaging were similar to those of nerve sheath tumors. The patient underwent open
      biopsy sampling of the lesion, and results of a pathological evaluation revealed
      hyaline-vascular type Castleman disease. She underwent radiotherapy and remains
      symptom-free with a radiographically stable lesion 1 year later. Although the
      disease has been reported to mimic a meningioma when encountered in intracranial
      locations, to the authors' knowledge, this is the first case of the disorder
      mimicking a nerve sheath tumor. When the diagnosis of Castleman disease is made,
      good results can be obtained with partial resection and radiotherapy.

PMID- 17542515
TI  - Selective treatment of an anterior spinal artery aneurysm with endosaccular coil
      therapy. Case report.
AB  - The authors report the case of a 12-year-old boy with spinal cord arteriovenous
      malformation (AVM) and an associated anterior spinal artery (ASA) aneurysm
      treated with selective coil placement in the context of subarachnoid hemorrhage
      (SAH). The patient presented with headache. Head computed tomography scanning
      revealed no abnormal findings. The cerebrospinal fluid was sampled and analyzed
      and a diagnosis of SAH was established. Investigation, including magnetic
      resonance imaging of the cord as well as cerebral and spinal angiography,
      revealed a conus medullaris AVM and a saccular aneurysm located on the ASA at the
      T-11 level. The aneurysm was thought to be responsible for the bleeding.
      Superselective ASA angiography showed that the aneurysm was at the bifurcation
      between a large coronal artery supplying the AVM and the ASA. The relation of the
      aneurysm's neck to the main spinal axis and the aneurysm's morphological features
      indicated that the lesion was suited for endosaccular coil therapy. The aneurysm
      was selectively occluded, using electrodetachable bare platinum coils. Follow-up
      angiography immediately after surgery and at 6 months thereafter demonstrated
      complete occlusion of the aneurysm and a perfectly patent anterior spinal axis.
      On clinical follow-up examination, the patient remained neurologically intact.
      When the morphological features of a spinal aneurysm and its relation with the
      anterior spinal axis are favorable, selective endosaccular coil placement can
      successfully be achieved.

PMID- 17542516
TI  - Multiple spinal extradural meningeal cysts presenting as acute paraplegia. Case
      report and review of the literature.
AB  - Multiple spinal extradural meningeal cysts are rare. To the authors' knowledge,
      there have been only four reported cases in the world literature. The authors
      report a case of multiple spinal extradural meningeal cysts in a 31-year-old
      woman presenting with acute paraplegia. Magnetic resonance imaging of the
      thoracolumbar spine revealed multiple extradural cystic lesions extending from T
      7 to T-8 and from T-12 to L-3. Intraoperative findings demonstrated a white,
      fibrous, and tense cyst filled with cerebrospinal fluid-like colorless fluid.
      Excision of the posterior wall of the symptomatic cyst was followed by immediate
      neurological improvement. The examination of the pathological specimen showed a
      thick duralike layer of collagen and an inner membrane of arachnoid that is often
      not found in these lesions. The final diagnosis was based on combined imaging,
      intraoperative, and histopathological findings. The authors review the literature
      and discuss the etiological, diagnostic, and therapeutic aspects of this lesion.

PMID- 17542517
TI  - Sacral epidural noncommunicating arachnoid cyst. Case report and review of the
      literature.
AB  - The authors examine the natural history of a spinal epidural arachnoid cyst and
      present their experience with its treatment in a 25-year-old man who presented
      with progressive cauda equina syndrome. Neuroimaging revealed two neighboring
      sacral epidural cysts. The cysts were completely removed via a sacral S1-4
      laminectomy; no communication with the subarachnoid space could be found. The
      patient's postoperative course was uneventful. He experienced progressive
      improvement and, finally, complete resolution of symptoms and no recurrence of
      the cyst. Nabors Type I sacral epidural arachnoid cysts are rare; in some cases
      their origins and the mechanism by which they cause deterioration in the
      patients' clinical condition are debatable. Findings in the present case support
      the idea that some of these cysts are noncommunicating but progressive in their
      clinical presentation. This lesion type is also known to occur intracranially. A
      brief review of the literature is provided.

PMID- 17542518
TI  - Diathermy testing: a novel method with electric knife stimulation to avoid nerve
      injuries during lumbar pedicle screw placement. Technical note.
AB  - The purpose of this retrospective study was to demonstrate the utility of
      diathermy in avoiding nerve injuries due to misplacement of lumbar pedicle screws
      (PSs). The authors used diathermy to assess whether a screw deviated from the
      pedicle by observing synchronous leg movements caused by intermittently touching
      an electric knife to the pedicular instrument. Diathermy was performed in 259
      cases in which 1301 PSs had been placed. Leg movements were observed in 36 cases,
      and the sensitivity of diathermy was 85.7%, with a specificity of 99.5%. No
      neurological complications associated with the placement of PSs were observed
      after adding diathermy testing to conventional methods. Diathermy testing may be
      a way to avoid nerve injuries during lumbar PS placement.

PMID- 17542519
TI  - Unilateral multilevel interlaminar fenestration instead of laminectomy or
      hemilaminectomy: an alternative surgical approach to intraspinal space-occupying
      lesions. Technical note.
AB  - Laminectomy is the most conventional dorsal approach to intraspinal space
      occupying lesions and may result in gradually increasing instability or deformity
      of the vertebral column. Less invasive procedures such as hemilaminectomy and
      osteoplastic laminotomy have been described by other authors, but an approach
      that interferes with spinal stability to an even lesser extent seems desirable.
      In an attempt to further reduce the need for bone removal, the authors used
      interlaminar fenestration (mostly unilateral) at one or more spinal levels to
      remove intramedullary, extramedullary, or extradural lesions, and even some
      lesions that extended over several spine segments. The authors present their
      experiences with this surgical approach in 78 patients harboring different
      intraspinal lesions. Up to 16 segments were fenestrated in one patient. Complete
      removal of the lesion was possible in most patients, and no postoperative spinal
      instabilities were observed in up to 8 years of follow up. Multilevel
      interlaminar fenestration, also called "multiple spinal keyhole surgery," is a
      feasible, safe, and effective approach to intraspinal lesions.

PMID- 17542520
TI  - Radiotherapy for a destructive cervicothoracic lesion from multiple myeloma. Case
      illustration.

PMID- 17542521
TI  - "You can't teach an old dog new tricks".

PMID- 17542522
TI  - The anterior approach for removal of ruptured cervical disks. 1958.

PMID- 17542523
TI  - Nonconvulsive status epilepticus in patients suffering spontaneous subarachnoid
      hemorrhage.
AB  - OBJECT: Nonconvulsive status epilepticus (NCSE) is an underrecognized and poorly
      understood complication of aneurysmal subarachnoid hemorrhage (SAH). The authors
      evaluated the risk factors, electroencephalographic (EEG) characteristics,
      hospital course, and clinical outcomes associated with NCSE in a population with
      SAH treated at a single institution. METHODS: The hospitalization and outcome
      data were reviewed in 11 patients who had received a diagnosis of NCSE and SAH.
      The study included individuals from a cohort of 389 consecutive patients with SAH
      who were treated between March 2003 and June 2005, and who were analyzed
      retrospectively. The patients' medical history, neurological grade, events of
      hospitalization, EEG morphological patterns, and disposition were analyzed.
      Advanced age, female sex, need for ventriculostomy, poor neurological grade (Hunt
      and Hess Grade III, IV, or V), thick cisternal blood clots, and structural
      lesions (intracerebral hemorrhage and stroke) were common in the population with
      NCSE. Patients with normal results on angiograms, good neurological grade (Hunt
      and Hess Grade I or II), and minimal SAH (Fisher Grade 1 or 2) were at lower
      risk. The most common ictal patterns were intermittent, and consisted of
      generalized periodic epileptiform discharges. Medical complications were also
      frequent, and the outcome of these patients was poor despite aggressive treatment
      regimens. CONCLUSIONS: Nonconvulsive status epilepticus is a devastating
      complication of SAH with a high rate of associated morbidity. Based on these
      findings it appears that the patients at highest risk for NCSE can be identified,
      and this should provide a basis for further studies designed to determine the
      clinical significance of various EEG patterns and to develop preventative
      strategies.

PMID- 17542524
TI  - Endovascular treatment of blood blister-like aneurysms of the internal carotid
      artery.
AB  - OBJECT: Because of its thin wall, an aneurysm arising from the posterior wall of
      the internal carotid artery (ICA), the so-called blood blister-like aneurysm
      (BBA), is difficult to manage surgically and is often associated with high
      morbidity and mortality rates. The authors treated these aneurysms
      endovascularly. In this paper, they present angiographic and clinical results
      obtained in patients with ICA BBAs treated endovascularly. METHODS: In seven
      patients with ICA BBAs who presented with subarachnoid hemorrhage, a total number
      of 12 endovascular treatments were performed, including seven endosaccular coil
      embolizations (four conventional, two stent-assisted and one balloon-assisted
      procedure) in four patients and five endovascular ICA trapping procedures in five
      patients. Repeated endovascular treatments were undertaken in four patients. In
      two patients, the endovascular treatment was performed after failure of surgical
      treatment (one case of rebleeding after clip placement and one aneurysmal
      regrowth after wrapping). A balloon occlusion test (BOT) was performed in all
      patients prior to ICA trapping. All four patients treated by endosaccular coil
      embolization showed aneurysmal regrowth. Neither stents nor balloons helpfully
      prevented aneurysmal regrowth. Of these four patients, two experienced
      rebleeding. These two patients remained vegetative at the last follow-up
      examination. After the BOT, ICA trapping was performed with coils and balloons
      without complication in five patients; excellent outcomes were achieved in all
      cases but one in which the patient had been in poor neurological condition due to
      rebleeding after surgical clip therapy. CONCLUSIONS: All ICA BBAs that were
      treated by endosaccular coil embolization exhibited regrowth of the aneurysm.
      Some of the lesions rebled. The majority of patients who underwent ICA trapping
      experienced excellent outcomes. Based on the authors' experiences, they suggest
      that ICA trapping including the lesion segment should be considered as a first
      option for definitive treatment if a BOT reveals satisfactory results. Regarding
      trapping methods, endovascular treatment may be preferred because of its
      convenience and safety.

PMID- 17542525
TI  - Variations in the response of interleukins in neurosurgical intensive care
      patients monitored using intracerebral microdialysis.
AB  - OBJECT: The aim of this study was to make a preliminary evaluation of whether
      microdialysis monitoring of cytokines and other proteins in severely diseased
      neurosurgical patients has the potential of adding significant information to
      optimize care, thus broadening the understanding of the function of these
      molecules in brain injury. METHODS: Paired intracerebral microdialysis catheters
      with high-cutoff membranes were inserted in 14 comatose patients who had been
      treated in a neurosurgical intensive care unit following subarachnoidal
      hemorrhage or traumatic brain injury. Samples were collected every 6 hours (for
      up to 7 days) and were analyzed at bedside for routine metabolites and later in
      the laboratory for interleukin (IL)-l and IL-6; in two patients, vascular
      endothelial growth factor and cathepsin-D were also checked. Aggregated
      microprobe data gave rough estimations of profound focal cytokine responses
      related to morphological tissue injury and to anaerobic metabolism that were not
      evident from the concomitantly collected cerebrospinal fluid data. Data regarding
      tissue with no macroscopic evidence of injury demonstrated that IL release not
      only is elicited in severely compromised tissue but also may be a general
      phenomenon in brains subjected to stress. Macroscopic tissue injury was strongly
      linked to IL-6 but not IL- lb activation. Furthermore, IL release seems to be
      stimulated by local ischemia. The basal tissue concentration level of IL-lb was
      estimated in the range of 10 to 150 pg/ml; for IL-6, the corresponding figure was
      1000 to 20,000 pg/ml. CONCLUSIONS: Data in the present study indicate that
      catheters with high-cutoff membranes have the potential of expanding
      microdialysis to the study of protein chemistry as a routine bedside method in
      neurointensive care.

PMID- 17542526
TI  - Train time as a quantitative electromyographic parameter for facial nerve
      function in patients undergoing surgery for vestibular schwannoma.
AB  - OBJECT: The authors describe a quantitative electromyographic (EMG) parameter for
      intraoperative monitoring of facial nerve function during vestibular schwannoma
      removal. This parameter is based on the automated detection of A trains, an EMG
      pattern that is known to be associated with postoperative facial nerve paresis.
      METHODS: For this study, 40 patients were examined. During the entire operative
      procedure, free-running EMG signals were recorded in muscles targeted by the
      facial nerve. A software program specifically designed for this purpose was used
      to analyze these continuous recordings offline. By automatically adding up time
      intervals during which A trains occurred, a quantitative parameter was
      calculated, which was named "train time." A strong correlation between the length
      of train time (measured in seconds) and deterioration of postoperative facial
      nerve function was demonstrated. Certain consecutive safety thresholds at 0.5 and
      10 seconds were defined. Their transgression reliably indicated postoperative
      facial nerve paresis. At less than a 10-second train time, discrete worsening,
      and at more than 10 seconds, profound deterioration of facial nerve function can
      be anticipated. CONCLUSIONS: Train time as a quantitative parameter was shown to
      be a reliable indicator of facial nerve paresis after surgery for vestibular
      schwannoma.

PMID- 17542527
TI  - Radiosurgery of growth hormone-producing pituitary adenomas: factors associated
      with biochemical remission.
AB  - OBJECT: The authors reviewed outcomes after stereotactic radiosurgery for
      patients with acromegaly and analyzed factors associated with biochemical
      remission. METHODS: Retrospective analysis was performed for 46 consecutive cases
      of growth hormone (GH)-producing pituitary adenomas treated by radiosurgery
      between 1991 and 2004. Biochemical remission was defined as a fasting GH less
      than 2 ng/ml and a normal age- and sex-adjusted insulin-like growth factor-I (IGF
      I) level while patients were not receiving any pituitary suppressive medications.
      The median follow up after radiosurgery was 63 months (range 22-168 months).
      Twenty-three patients (50%) had biochemical remission documented at a median of
      36 months (range 6-63 months) after one radiosurgical procedure. The actuarial
      rates of biochemical remission at 2 and 5 years after radiosurgery were 11 and
      60%, respectively. Multivariate analysis showed that IGF-I levels less than 2.25
      times the upper limit of normal (hazard ratio [HR] 2.9, 95% confidence interval
      [CI] 1.2-6.9, p = 0.02) and the absence of pituitary suppressive medications at
      the time of radiosurgery (HR 4.2, 95% CI 1.4-13.2, p = 0.01) correlated with
      biochemical remission. The incidence of new anterior pituitary deficits was 10%
      at 2 years and 33% at 5 years. CONCLUSIONS: Discontinuation of pituitary
      suppressive medications at least 1 month before radiosurgery significantly
      improved endocrine outcomes for patients with acromegaly. Patients with GH
      producing pituitary adenomas should not undergo further radiation therapy or
      surgery for at least 5 years after radiosurgery because GH and IGF-I levels
      continue to normalize over that interval.

PMID- 17542528
TI  - Gamma knife surgery for trigeminal schwannoma.
AB  - OBJECT: Trigeminal schwannomas are rare intracranial tumors. In the past,
      resection and radiation therapy were the mainstays of their treatment. More
      recently, neurosurgeons have begun to use radiosurgery in the treatment of
      trigeminal schwannomas because of its successful use in the treatment of
      vestibular schwannomas. In this article the authors evaluate the radiological and
      clinical outcomes in a series of patients in whom Gamma Knife surgery (GKS) was
      used to treat trigeminal schwannomas. METHODS: Twenty-six patients with
      trigeminal schwannomas underwent GKS at the University of Virginia Lars Leksell
      Gamma Knife Center between 1989 and 2005. Five of these patients had
      neurofibromatosis and one patient was lost to follow up. The median tumor volume
      was 3.96 cm(3), and the mean follow-up period was 48.5 months. The median
      prescription radiation dose was 15 Gy, and the median prescription isodose
      configuration was 50%. There was clinical improvement in 18 patients (72%), a
      stable lesion in four patients (16%), and worsening of the disease in three
      patients (12%). On imaging, the schwannomas shrank in 12 patients (48%), remained
      stable in 10 patients (40%), and increased in size in three patients (12%). These
      results were comparable for primary and adjuvant GKSs. No tumor growth following
      GKS was observed in the patients with neurofibromatosis. CONCLUSIONS: Gamma Knife
      surgery affords a favorable risk-to-benefit profile for patients harboring
      trigeminal schwannomas. Larger studies with open-ended follow-up review will be
      necessary to determine the long-term results and complications of GKS in the
      treatment of trigeminal schwannomas.

PMID- 17542529
TI  - Stereotactic radiation treatment for recurrent nonbenign meningiomas.
AB  - OBJECT: The authors analyzed the results of stereotactic radiosurgery (SRS) and
      stereotactic radiotherapy (SRT) for the treatment of recurrent meningiomas that
      were described at initial resection as showing aggressive, atypical, or malignant
      features (nonbenign). METHODS: Twenty-five patients who underwent SRS and/or SRT
      for nonbenign meningiomas between December 1992 and August 2004 were included.
      Thirteen of these patients underwent treatment for multiple primary or recurrent
      lesions. In all, 52 tumors were treated. All histological sections were reviewed
      and reclassified according to World Health Organization (WHO) 2000 guidelines as
      benign (Grade I), atypical (Grade II), or anaplastic (Grade III) meningiomas. The
      median follow-up period was 42 months. Seventeen (68%) of the cases were
      reclassified as follows: WHO Grade I (five cases), Grade II (11 cases), and Grade
      III (one case). Malignant progression occurred in eight cases (32%) during the
      follow-up period; these cases were considered as a separate group. The 3-year
      progression-free survival (PFS) rates for the Grades I, II, and III, and
      malignant progression groups were 100, 83, 0, and 11%, respectively (p < 0.001).
      In the Grade II group, the 3-year PFS rates for patients treated with SRS and SRT
      were 100 and 33%, respectively (p = 0.1). After initial treatment, 22 new tumors
      required treatment using SRS or SRT; 17 (77%) of them occurred inside the
      original resection cavity. Symptomatic edema developed in one patient (4%).
      CONCLUSIONS: Stereotactic radiation treatment provided effective local control of
      "aggressive" Grade I and Grade II meningiomas, whereas Grade III lesions were
      associated with poor outcome. The outcome of cases in the malignant progression
      group was intermediate between that of the Grade II and Grade III groups, with
      the lesions showing a tendency toward malignancy.

PMID- 17542530
TI  - Surgical and endovascular management of symptomatic posterior circulation
      fusiform aneurysms.
AB  - OBJECT: Patients with fusiform aneurysms can present with subarachnoid hemorrhage
      (SAH), mass effect, ischemia, or unrelated symptoms. The absence of an aneurysm
      neck impedes the direct application of a clip and endovascular coil deployment.
      To evaluate the effects of their treatments, the authors retrospectively analyzed
      a consecutive series of patients with posterior circulation fusiform aneurysms
      treated at Stanford University Medical Center between 1991 and 2005. METHODS:
      Forty-nine patients (mean age 53 years, male/female ratio 1.2:1) treated at the
      authors' medical center form the basis of the analysis. Twenty-nine patients
      presented with an SAH. The patients presenting without SAH had cranial nerve
      dysfunction (five patients), symptoms of mass effect (eight patients), ischemia
      (six patients), or unrelated symptoms (one patient). The aneurysms were located
      on the vertebral artery (VA) or posterior inferior cerebellar artery (PICA) (21
      patients); vertebrobasilar junction (VBJ) or basilar artery (BA) (18 patients);
      and posterior cerebral artery (PCA) (10 patients). Pretreatment clinical grades
      were determined using the Hunt and Hess scale; for patients with unruptured
      aneurysms (Hunt and Hess Grade 0) functional subgrades were added. Outcome was
      evaluated using the Glasgow Outcome Scale (GOS) score during a mean follow-up
      period of 33 months. Overall long-term outcome was good (GOS Score 4 or 5) in
      59%, poor (GOS Score 2 or 3) in 16%, and fatal (GOS Score 1) in 24% of the
      patients. In a univariate analysis, poor outcome was predicted by age greater
      than 55 years, VBJ location, pretreatment Hunt and Hess grade in patients
      presenting with SAH, and incomplete aneurysm thrombosis after endovascular
      treatment. In a multivariate analysis, age greater than 55 years was the
      confounding factor predicting poor outcome. Stratification by aneurysm location
      removed the effect of age. Of 13 patients with residual aneurysm after treatment,
      five (38%) subsequently died of SAH (three patients) or progressive mass
      effect/brainstem ischemia (two patients). CONCLUSIONS: Certain posterior
      circulation aneurysm locations (PCA, VA-PICA, and BA-VBJ) represent separate
      disease entities affecting patients at different ages with distinct patterns of
      presentation, treatment options, and outcomes. Favorable overall long-term
      outcome can be achieved in 90% of patients with PCA aneurysms, in 60% of those
      with VA-PICA aneurysms, and in 39% of those with BA-VBJ aneurysms when using
      endovascular and surgical techniques. The natural history of the disease was poor
      in patients with incomplete aneurysm thrombosis after treatment.

PMID- 17542531
TI  - Cystic vestibular schwannomas: a possible role of matrix metalloproteinase-2 in
      cyst development and unfavorable surgical outcome.
AB  - OBJECT: The authors evaluated the clinical manifestations and surgical results in
      patients with cystic vestibular schwannoma (VS), and investigated the matrix
      metalloproteinase (MMP) expression of the cyst fluid and wall in an attempt to
      elucidate the pathogenesis and characteristics of this disease. METHODS: The
      clinical and neuroimaging features, perioperative findings, and surgical outcomes
      in 24 cases of cystic VS and 82 cases of solid VS, all of which were treated
      using the suboccipital approach, were retrospectively compared. To evaluate the
      role of MMP in cystic VS, gelatin zymography and immunohistochemical studies of
      the cyst fluid, wall, and solid portion were performed in nine cases of this
      disease. The mean duration of symptoms was shorter (14.0 months compared with
      26.1 months; p = 0.04) and the mean size of the tumor was larger (43.8 mm
      compared with 34.2 mm; p = 0.048) in the cystic than the solid VS group. Although
      gross-total resection was easier to accomplish in this group (100% compared with
      84.1%), adhesion to the facial nerve was more frequent (62.5% compared with
      48.8%; p = 0.042). On gelatin zymography studies, MMP-2 expression was
      ubiquitously observed in all cyst fluids. Immunohistochemical analysis of the
      cyst wall showed that MMP-2 was apparently localized to the tumor cells on the
      luminal inner surface, adjacent to the cyst cavity. CONCLUSIONS: Resection of
      cystic VS is complicated by severe adhesion of the tumor capsule to the facial
      nerve and the large size of the lesion. The authors believe that MMP-2 may be
      involved in the pathogenesis of cyst formation or in its enlargement and may
      aggravate adhesion to the facial nerve, either by promoting the enlargement of
      the tumor or engendering the degradation of the tumor-nerve barrier
      proteolytically.

PMID- 17542532
TI  - A new method for superselective middle cerebral artery infusion in the rat.
AB  - OBJECT: Selective intraarterial drug delivery is used to achieve enhanced local
      uptake with reduced systemic side effects. In the present paper the authors
      describe and characterize a new microcatheter-based model of superselective
      perfusion of the middle cerebral artery (MCA) in rats combined with blockade of
      blood flow through the MCA. METHODS: Selectivity of administration was shown by
      infusion of Evans blue which diffusely stained the MCA territory, indicating an
      increased permeability of the blood-brain barrier during the blockade of blood
      flow to the MCA. Perfusion of autologous blood through the microcatheter resulted
      in a flow rate-related increase in the cerebral blood flow measured by laser
      Doppler flowmetry. Similarly, infusion of an artificial O2 carrier, Oxycyte, was
      accompanied by an increase in tissue oxygenation as measured using a Licox
      sensor. Blockade of blood flow to the MCA with the new microcatheter for an
      extended period of time resulted in the development of ischemia, which was
      comparable to that induced by intravascular occlusion using a silicone-coated
      thread. In a 24-hour MCA occlusion model, selective administration of a low dose
      of MK-801 (0.3 mg/kg body weight) resulted in a significantly smaller infarct
      volume than systemic application (339 +/- 53 mm(3) compared with 508 +/- 26
      mm(3), p < 0.001). CONCLUSIONS: This new model of superselective MCA infusion is
      a valuable tool for investigating the effect of selective delivery and enhanced
      drug uptake into cerebral ischemic tissue. Without constant blockade of blood
      flow through the MCA it may also be useful for enhanced drug uptake, gene
      transfer, or application of stem cells in other neuropathological conditions.

PMID- 17542533
TI  - Vasospasm.

PMID- 17542534
TI  - Neurokinin-1 receptor antagonism in a rat model of subarachnoid hemorrhage:
      prevention of upregulation of contractile ETB and 5-HT1B receptors and cerebral
      blood flow reduction.
AB  - OBJECT: Cerebral vasospasm following subarachnoid hemorrhage (SAH) leads to
      reduced cerebral blood flow (CBF) and to cerebral ischemia, in some cases even
      producing infarction and long-term disability. The goal of the present study was
      to investigate the hypothesis that inhibition of neurokinin-1 receptors (NK1Rs)
      by administration of L-822429 blunts the decrease in CBF as well as
      cerebrovascular receptor upregulation in an animal model of SAH. METHODS:
      Subarachnoid hemorrhage was induced in rats by injection of 250 microl of blood
      into the prechiasmatic cistern. The NK1R inhibitor L-822429 was injected
      intracisternally 30 minutes and 24 hours after the induction of SAH. Two days
      after SAH induction, the basilar arteries were harvested, and contractile
      responses to endothelin-1 (ET-I, an ETA- and ETB-receptor agonist) and 5
      carboxamidotryptamine (a 5-hydroxytryptamine- I1 [5-HT1]-receptor agonist) were
      investigated using sensitive myographs. To determine whether NKIR inhibition had
      an influence on local CBF after post-SAH, a quantitative autoradiographic
      technique was used. After SAH, the vascular receptor phenotype was changed in
      cerebral arteries through upregulation of contractile ET, and 5-HT1B receptors,
      while regional and total CBF were markedly reduced. Treatment with the selective
      NK1R inhibitor L-822429 prevented both the receptor upregulation and the
      reduction in regional and global CBF. CONCLUSIONS: The data reveal the
      coregulation of vascular receptor changes and blood flow effects, and also show
      that interaction with a small-molecule NK1R antagonist is a promising area of
      focus for the development of specific treatments for SAH.

PMID- 17542535
TI  - The surgical anatomy of ulnar and median nerve communications in the palmar
      surface of the hand.
AB  - OBJECT: Sensation in the palmar surface of the digits is supplied by the median
      and ulnar nerves, with the boundary classically being the midline of the ring
      finger. Overlap and variations of this division exist, and a communicating branch
      between the ulnar and median nerve could potentially explain further variations
      in digital sensory innervations. The aim of this study was to examine the origin
      and distribution of the communicating branch between the ulnar and median nerves
      and to apply such findings to the risk involved in surgical procedures in the
      hand. METHODS: The authors grossly and endoscopically examined 200 formalin-fixed
      adult human hands obtained in 100 cadavers, and a communicating branch was found
      to be present in 170 hands (85%). Of the specimens with communicating branches,
      the authors were able to identify four notable types representing different
      points of connections of the branches. The most common, Type I (143 hands,
      84.1%), featured a communicating branch that originated proximally from the ulnar
      nerve and proceeded distally to join the median nerve. Type II (12 hands, 7.1%)
      designated a communicating branch that originated proximally from the median
      nerve and proceeded distally to join the ulnar nerve. Type III (six hands, 3.5%)
      designated a communicating branch that traversed perpendicularly between the
      median and ulnar nerves in such a way that it was not possible to determine which
      nerve served as the point of origin. Type IV (nine hands, 5.3%) designated a
      mixed type in which multiple communicating branches existed, arising from both
      ulnar and median nerves. CONCLUSIONS: According to the origin and distribution of
      these branching patterns, the investigators were able to define a risk area in
      which the communicating branch(es) may be subject to iatrogenic injury during
      common hand procedures.

PMID- 17542536
TI  - Microsurgical anatomy of the mesencephalic veins.
AB  - OBJECT: The mesencephalic veins drain crucial brainstem areas. Due to the
      narrowness of the tentorial notch, these veins can become obstructed as a result
      of herniation or surgery, leading to hemorrhage and severe consequences for the
      patient. There is little in the literature about the mesencephalic veins. The aim
      of this study was to perform an exact analysis of their microanatomy. METHODS:
      Fifty-two cadaveric hemispheres were examined under an operating microscope, and
      measurements were made with a digital caliper. The authors focused on the basal
      vein (BV), pontomesencephalic vein (PMV), peduncular vein (PV), lateral
      mesencephalic vein (LMV), and other smaller veins. The PMV was identified in
      84.6% of specimens (mean diameter 0.54 mm); the PV, in 86.5% (mean diameter 0.86
      mm); and the LMV, in 100% (mean diameter 1.07 mm). Four types of LMV were
      identified on the basis of the vein's course. Other smaller veins were also
      differentiated according to whether they drained mainly the cerebral peduncle,
      the lemniscal trigone, or the tectum. These veins and their junctions with other
      veins were depicted. CONCLUSIONS: A thorough understanding of the microanatomy of
      the mesencephalic veins is crucial in brainstem surgery in order to avoid brain
      damage due to venous infarction and subsequent edema. Because knowledge of the
      course, variations, and outflow system of these veins could improve surgical
      outcome, they warrant special attention during surgery.

PMID- 17542537
TI  - Surgical anatomy and landmarks for the basal vein of rosenthal.
AB  - OBJECT: The basal vein of Rosenthal (BV) courses from the premesencephalic
      cistern, through the ambient cistern, and terminates in the quadrigeminal
      cistern. The aim of this study was to describe and quantitate the surgical
      anatomy of this structure and specifically to provide landmarks for identifying
      this vessel along its course. These data may be of use, for example, to surgeons
      using subtemporal operative approaches through regions where this vessel is
      concealed. METHODS: The authors examined 15 latex-injected adult cadaveric brains
      (30 sides) to delineate the morphological characteristics of the BV. Dissections
      of the BV were then performed and measurements were made between this structure
      and the tentorial incisura at the anterior, middle, and posterior borders of the
      lateral midbrain. All specimens were found to have a left and right BV with
      varying morphological characteristics. The mean distance between the BV and
      posterior cerebral artery at the midpoint of the lateral midbrain was 16 mm. The
      BV was always found superomedial to the posterior cerebral artery along the
      lateral aspect of the midbrain, and the BV ranged in diameter from 1 to 5 mm. The
      BV drained into the vein of Galen in all but two specimens. The mean distances
      from the tentorial edge to the BV at the anterior, middle, and posterior borders
      of the lateral midbrain were 11, 1 3, and 4 mm, respectively. No statistically
      significant differences were found when comparing left and right sides or male
      and female specimens. CONCLUSIONS: The authors hope that these data will help the
      neurosurgeon operating near the BV to avoid injury to this important structure.

PMID- 17542538
TI  - Combined transarterial N-butyl cyanoacrylate and coil embolization of direct
      carotid-cavernous fistulas. Report of two cases.
AB  - The authors report two cases of traumatic carotid-cavernous fistulas treated
      successfully with combined N-butyl cyanoacrylate glue and coil embolization via a
      transarterial approach. In both cases complete occlusion of the fistula was
      achieved, with preservation of the parent carotid artery. Casting of the
      cavernous sinus with a liquid embolic agent was well tolerated and produced no
      complications of cranial nerve palsy. This technique provides interventionalists
      with yet another treatment option in these often complex cases.

PMID- 17542539
TI  - Stent fracture and restenosis after placement of a drug-eluting device in the
      vertebral artery origin and treatment with the stent-in-stent technique. Report
      of two cases.
AB  - The authors report two cases of stent fracture and restenosis after placement of
      a drug-eluting device in the vertebral artery (VA) origin, and describe
      management of restenosis with the stent-in-stent technique. Two women, one 62 and
      the other 67 years of age, underwent stent placement in the VA origin to treat
      symptomatic and angiographically significant stenosis in this vessel. Sirolimus
      eluting coronary stents (Cypher) were used in both cases. Four months after
      placement of the devices, the symptoms recurred. Follow-up angiography performed
      5 months after insertion of the devices revealed a transverse stent fracture with
      separation of the fragments and severe in-stent restenosis in both cases. The
      restenoses were treated with reinsertion of coronary stents (Cypher and Jostent
      FlexMaster) by using the stent-in-stent technique. After stent reinsertion, the
      patients exhibited relief of symptoms. This paper is the first report of fracture
      in a drug-eluting stent and restenosis after stent placement in the VA origin.
      Restenosis caused by such a fracture can be managed successfully by performing
      the stent-in-stent maneuver. The physical properties of metallic devices, stent
      strut geometry, and anatomical peculiarities of the subclavian artery may be
      associated with stent fractures. Earlier follow-up angiography studies (within 6
      months) are warranted.

PMID- 17542540
TI  - Transcranial puncture through the parietal and mastoid foramina for the treatment
      of dural fistulas. Report of four cases.
AB  - In this report the authors describe the endovascular treatment of dural
      arteriovenous fistulas (DAVFs) through transcranial puncture of the feeding
      arteries. Four patients had DAVFs that were fed by occipital arteries (OAs) that
      supplied blood to the intracranial meningeal arteries via the transcranial
      branches and coursed through the parietal and mastoid foramina. Due to the
      excessive tortuosity of the OA, conventional endovascular navigation had failed
      in all cases. Transcranial puncture of the meningeal feeding arteries was
      performed through the parietal or mastoid foramen, allowing navigation with a
      microcatheter until the level of the shunts. Complete cure of the DAVF was
      attained in all patients after injection of acrylic glue.

PMID- 17542541
TI  - Progressive perianeurysmal edema induced after endovascular coil embolization.
      Report of three cases and review of the literature.
AB  - The authors report three cases of progressive vasogenic brain edema surrounding a
      cerebral aneurysm after endovascular coil embolization. In all three cases
      embolization was incomplete due to the aneurysms' large sizes and wide necks.
      Follow-up magnetic resonance imaging revealed de novo vasogenic brain edema
      surrounding the aneurysms 3 to 6 months after the initial treatment. The edema
      progressed in parallel with regrowth of the aneurysms. All three aneurysms were
      deep in the brain parenchyma and showed intramural enhancement, suggesting
      hemorrhage or inflammation. Each patient underwent a second embolization for the
      aneurysm regrowth, which resulted in improvement of the edema. Based on the
      findings in these cases and review of the literature, it is suggested that
      incomplete occlusion of larger aneurysms that are deep within the brain may lead
      to a disorganized intraluminal thrombosis, aneurysm pulsing, and intramural
      hemorrhage or inflammation, all of which are associated with brain edema
      following aneurysm recanalization and regrowth. It should be kept in mind that
      incomplete embolization of larger aneurysms may cause such malignant change and
      that this complication may occur after endovascular treatment.

PMID- 17542542
TI  - Medial plantar nerve compression by a tibial artery schwannoma. Case report.
AB  - The authors describe the case of a patient with a novel cause of medial plantar
      symptoms due to extrinsic compression by a schwannoma arising within the
      adventitia of the tibial artery in the ankle region. Additionally they provide
      the operative, histological, and imaging findings.

PMID- 17542543
TI  - Epstein-Barr virus infection as a complication of transplantation of a nerve
      allograft from a living related donor. Case report.
AB  - Reconstruction of extensive nerve defects is hampered by the amount of autogenous
      nerve tissue available for transplantation and by donor site morbidity. Nerve
      allografts, being of foreign origin and potentially unlimited in supply, provide
      a solution to these problems. Studies have shown that nerve allotransplants
      require immunosuppression only until end-organ connections are made and that
      immunosuppressant therapy may be subsequently discontinued with no negative
      effect on functional outcome. Also, recent experimental and clinical focus has
      been on shorter periods of immunosuppression in order to reduce risk, even
      stopping immunosuppression after regeneration has reached the distal suture line
      rather than before recovery of end-organ connections. In the pediatric
      population, the increased disease burden and increased potential for nerve
      regeneration as well as the frequent availability of a living related donor make
      allografts all the more attractive as solutions to nerve reconstructive problems.
      Nevertheless, the risks of immunosuppression must not be underemphasized, and
      they deserve more attention in the current nerve transplantation literature. The
      authors report on a child who, at the age of 1 year, received a nerve allograft
      from a living related donor who was positive for Epstein-Barr virus (EBV). The
      child quickly developed a symptomatic EBV infection concurrent with
      immunosuppressant drug therapy. The immunosuppression regimen was stopped
      prematurely, and the patient suffered only a short illness, but the EBV infection
      could have developed into a life-threatening posttransplant lymphoproliferative
      disorder (PTLD). The patient is consequently predisposed to develop PTLD and will
      have to be monitored for the rest of his life. This case highlights the
      importance of considering the potentially fatal risks associated with this
      elective procedure. Future studies are needed to quantify and minimize this
      complication. Nevertheless, it should be weighed against the potential functional
      benefit from using nerve allografts.

PMID- 17542544
TI  - Use of fenestrated aneurysm clips in microvascular decompression surgery.
      Technical note and case series.
AB  - /The standard techniques of microvascular decompression (MVD) surgery in which
      implant materials such as shredded Teflon felt are used may be inadequate in some
      complex cases. The authors evaluated the use of fenestrated aneurysm clips to
      maintain transposition of culprit vessels in patients with trigeminal neuralgia
      (TN) and hemifacial spasm (HFS). The authors conducted a retrospective review of
      MVD operations in which the culprit vessel was transposed and then maintained in
      position with a fenestrated aneurysm clip secured in position by suturing it to
      the dura mater. Among a consecutive series of more than 450 MVD surgeries, the
      fenestrated aneurysm clip sling was used in eight of the last 100 cases: six for
      HFS and two for TN. The follow-up period ranged from 1 to 13 months, and complete
      symptom resolution was noted in seven of the eight patients. No patient exhibited
      evidence of any surgical complications. This approach can be safely performed in
      complicated MVD cases such as reoperations and transpositions of long ectatic
      arteries. To the best of the authors' knowledge this is the first report in which
      the use of fenestrated aneurysm clips in MVD surgery is described.

PMID- 17542545
TI  - An adjustable nasal speculum for the extended transsphenoidal approach. Technical
      note.
AB  - The authors describe a newly modified nasal speculum that enables panoramic
      visualization of the deep and wide surgical field created via an extended
      transsphenoidal approach. In their approach, the bone around the piriform
      aperture is not removed.

PMID- 17542546
TI  - Amaurosis fugax caused by retinal artery vasospasm. Case illustration.

PMID- 17542547
TI  - Surgery or gamma knife.

PMID- 17542548
TI  - Magnsium and vasospasm.

PMID- 17542549
TI  - Growth hormone.

PMID- 17542550
TI  - Non-heme Fe(IV)-oxo intermediates.
AB  - High-valent non-heme iron-oxo intermediates have been proposed for decades as the
      key intermediates in numerous biological oxidation reactions. In the past three
      years, the first direct characterization of such intermediates has been provided
      by studies of several alphaKG-dependent oxygenases that catalyze either
      hydroxylation or halogenation of their substrates. In each case, the Fe(IV)-oxo
      intermediate is implicated in cleavage of the aliphatic C-H bond to initiate
      hydroxylation or halogenation. The observation of non-heme Fe(IV)-oxo
      intermediates and Fe(II)-containing product(s) complexes with almost identical
      spectroscopic parameters in the reactions of two distantly related alphaKG
      dependent hydroxylases suggests that members of this subfamily follow a conserved
      mechanism for substrate hydroxylation. In contrast, for the alphaKG-dependent non
      heme iron halogenase, CytC3, two distinct Fe(IV) complexes form and decay
      together, suggesting that they are in rapid equilibrium. The existence of two
      distinct conformers of the Fe site may be the key factor accounting for the
      divergence of the halogenase reaction from the more usual hydroxylation pathway
      after C-H bond cleavage. Distinct transformations catalyzed by other mononuclear
      non-heme enzymes are likely also to involve initial C-H bond cleavage by Fe(IV)
      oxo complexes, followed by diverging reactivities of the resulting Fe(III)
      hydroxo/substrate radical intermediates.

PMID- 17542551
TI  - Simple one-pot preparation of water-soluble, cysteine-reactive cyanine and
      merocyanine dyes for biological imaging.
AB  - A simple one-pot-procedure for preparation of protein-reactive, water-soluble
      merocyanine and cyanine dyes has been developed. The 1-(3-ammoniopropyl)-2,3,3
      trimethyl-3H-indolium-5-sulfonate bromide (1) was used as a common starting
      intermediate. The method allows easy preparation of dyes with chloro- and
      iodoacetamide side chains for covalent attachment to cysteine. By placing a
      sulfonato group directly on the dye fluorophore system, dyes with high
      fluorescence quantum yields in water were generated. Both iodo- and
      chloroacetamido derivatives were shown to be useful in protein labeling. Less
      reactive chloroacetamides will be preferential for selective labeling of the most
      reactive cysteines.

PMID- 17542552
TI  - Concept for facilitating analyst-mediated interpretation of qualitative
      chromatographic-mass spectral data: an alternative to manual examination of
      extracted ion chromatograms.
AB  - A chemometrics-based data analysis concept has been developed as a substitute for
      manual inspection of extracted ion chromatograms (XICs), which facilitates rapid,
      analyst-mediated interpretation of GC- and LC/MS(n) data sets from samples
      undergoing qualitative batchwise screening for prespecified sets of analytes.
      Automatic preparation of data into two-dimensional row space-derived scatter
      plots (row space plots) eliminates the need to manually interpret hundreds to
      thousands of XICs per batch of samples while keeping all interpretation of raw
      data directly in the hands of the analyst-saving great quantities of human time
      without loss of integrity in the data analysis process. For a given analyte, two
      analyte-specific variables are automatically collected by a computer algorithm
      and placed into a data matrix (i.e., placed into row space): the first variable
      is the ion abundance corresponding to scan number x and analyte-specific m/z
      value y, and the second variable is the ion abundance corresponding to scan
      number x and analyte-specific m/z value z (a second ion). These two variables
      serve as the two axes of the aforementioned row space plots. In order to collect
      appropriate scan number (retention time) information, it is necessary to analyze,
      as part of every batch, a sample containing a mixture of all analytes to be
      tested. When pure standard materials of tested analytes are unavailable, but
      representative ion m/z values are known and retention time can be approximated,
      data are evaluated based on two-dimensional scores plots from principal component
      analysis of small time range(s) of mass spectral data. The time-saving efficiency
      of this concept is directly proportional to the percentage of negative samples
      and to the total number of samples processed simultaneously.

PMID- 17542553
TI  - Principle of two-dimensional characterization of copolymers.
AB  - Two-dimensional polymer characterization is used for a simultaneous analysis of
      molar masses and chemical heterogeneities (e.g., end groups, copolymer
      composition, etc.). This principle is based on coupling of two different
      chromatographic modes. Liquid adsorption chromatography at critical conditions
      (LACCC) is applied for a separation according to the chemical heterogeneity,
      whereas in the second-dimension fractions are analyzed with regard to their molar
      mass distribution by means of size exclusion chromatography (SEC). Because
      appropriate standards for a calibration of the SEC are seldom available, matrix
      assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF
      MS) was used to substitute the SEC. The LACCC-MALDI MS coupling enables acquiring
      additional structural information on copolymer composition, which can
      considerably enhance the performance of this coupled method.

PMID- 17542554
TI  - Matrix-free laser desorption/ionization-mass spectrometry using self-assembled
      germanium nanodots.
AB  - A novel ionization platform for matrix-free laser desorption/ionization-mass
      spectrometry (LDI-MS) was developed using self-assembled germanium nanodots
      (GeNDs) of uniform size (approximately 150 - 200-nm width and approximately 50-nm
      height) grown on a silicon wafer produced by molecular beam epitaxy. The
      performance of LDI-MS using GeNDs (GeND-MS) was investigated through measurements
      of a broad range of analytes, including peptides, proteins, synthetic oligomers,
      and polymer additives. Mass spectra of tryptic digests were clearly observed even
      for the mass range lower than m/z 800 without obstructive peaks. A detection
      limit of subfemtomole level was achieved for angiotensin-I. The upper limit of
      detectable mass range was approximately 17 kDa (myoglobin). GeND-MS also has
      potential for application to the characterization of industrial compounds. Almost
      accurate molecular weight distribution was obtained for a nonionic surfactant
      (Triton X-100) and for poly(ethylene glycol) oligomer. Furthermore, a brominated
      flame retardant, tetrabromobisphenol-A bis(2,3-dibromopropyl ether), was
      successfully ionized with less fragmentation, a result not obtainable by matrix
      assisted laser desorption/ionization-mass spectrometry or desorption/ionization
      on porous silicon-mass spectrometry.

PMID- 17542555
TI  - Thermoelectric manipulation of aqueous droplets in microfluidic devices.
AB  - This article describes a method for manipulating the temperature inside aqueous
      droplets, utilizing a thermoelectric cooler to control the temperature of select
      portions of a microfluidic chip. To illustrate the adaptability of this approach,
      we have generated an "ice valve" to stop fluid flow in a microchannel. By taking
      advantage of the vastly different freezing points for aqueous solutions and
      immiscible oils, we froze a stream of aqueous droplets that were formed on-chip.
      By integrating this technique with cell encapsulation into aqueous droplets, we
      were also able to freeze single cells encased in flowing droplets. Using a live
      dead stain, we confirmed the viability of cells was not adversely affected by the
      process of freezing in aqueous droplets provided cryoprotectants were utilized.
      When combined with current droplet methodologies, this technology has the
      potential to both selectively heat and cool portions of a chip for a variety of
      droplet-related applications, such as freezing, temperature cycling, sample
      archiving, and controlling reaction kinetics.

PMID- 17542556
TI  - Role of carbon nanotubes in analytical science.
AB  - Analytical science has gone through several turning points, one of the most
      decisive of which was signaled by the development and massive use of instruments
      for analytical purposes. One other pivotal turning point was the inception of
      computer science, which not only enabled the automatic control of analytical
      systems but also facilitated the acquisition of vast amounts of data and their
      processing with the aid of chemometrics. Following the growing significance of
      automation and miniaturization in recent times, the early 21st century is
      witnessing the rise of nanotechnology as a new, increasingly important,
      revolutionary trend in science in general and analytical science in particular.
      The ability to exploit molecular interactions between analytes and nanoparticles
      has opened up new, challenging prospects in this area. Good proof of the interest
      aroused by nanoparticles is the large number of papers on their use in quantum
      dots, fullerene, aurum nanoparticles, or carbon nanotubes published in recent
      years.

PMID- 17542557
TI  - Development of an automated cylindrical ion trap mass spectrometer for the
      determination of atmospheric volatile organic compounds.
AB  - Volatile organic compounds released from the biosphere are known to have a large
      impact on atmospheric chemistry. Field instruments for the detection of these
      trace gases are often limited by the lack of instrument portability and the
      inability to distinguish compounds of interest from background or other
      interfering compounds. We have developed an automated sampling and
      preconcentration system, coupled to a lightweight, low-power cylindrical ion trap
      mass spectrometer. The instrument was evaluated by measuring isoprene
      concentrations during a field campaign at the University of Michigan Biological
      Station PROPHET lab. Isoprene was preconcentrated by sampling directly into a
      short capillary column precooled without the aid of cryogens. The capillary
      column was then rapidly heated by moving the column to a preheated region to
      obtain fast separation of isoprene from other components, followed by detection
      with a cylindrical ion trap. This combination yielded a detection limit of
      approximately 80 ppt (parts per trillion) for isoprene with a measurement
      frequency of one sample every 11 min. The data obtained by the automated sampling
      and preconcentration system during the PROPHET 2005 campaign were compared to
      those of other field instruments measuring isoprene at this site in an
      intercomparison exercise. The intercomparisons suggest the new inlet system, when
      coupled with this ion trap detector, provides a viable field instrument for the
      fast, precise, and quantitative determination of isoprene and other trace gases
      over a variety of atmospheric conditions.

PMID- 17542558
TI  - Direct analysis in real time for reaction monitoring in drug discovery.
AB  - Direct analysis in real time (DART) is a novel ionization technique that provides
      for the rapid ionization of small molecules under ambient conditions. In this
      study, several commercially available drugs as well as actual compounds from drug
      discovery research were examined by LC/UV/ESI-MS and DART interfaced to a
      quadrupole mass spectrometer. For most compounds, the molecular ions observed by
      ESI-MS were observed by DART/MS. DART/MS was also studied as a means to quickly
      monitor synthetic organic reactions and to obtain nearly instantaneous molecular
      weight confirmations of final products in drug discovery. For simple, synthetic
      organic transformations, the trends in the intensities of the mass spectral
      signals for the reactant and product obtained by DART/MS scaled closely with
      those of the diode array or the total ion chromatogram obtained by LC/UV/ESI-MS.
      In summary, DART is a new tool that complements electrospray ionization for the
      rapid ionization and subsequent mass spectral analysis of compounds in drug
      discovery.

PMID- 17542559
TI  - On-line dynamic titration: determination of dissociation constants for
      noncovalent complexes using Gaussian concentration profiles by electrospray
      ionization mass spectrometry.
AB  - A new method for determination of dissociation constants (Kd) using on-line
      titration by electrospray ionization mass spectrometry is presented. Unlike in
      common titration experiments, where a set of discrete solutions with a fixed
      concentration of host and increasing concentration of guest is measured, here a
      continuous Gaussian concentration profile of guest, formed by band-broadening
      dispersion during passage through a long tubing, is utilized. An equation
      allowing access to dissociation constant values from experimental data fit to a
      1:1 binding model was derived and incorporated into an in-house-written computer
      program for automated data processing. The new method is demonstrated for
      noncovalent complexes of cinchona alkaloid carbamate chiral selectors with N
      dinitrobenzoylleucine enantiomers and a series of cyclodextrins with sulfonated
      azo dyes.

PMID- 17542560
TI  - An aggregation-prone intermediate species is present in the unfolding pathway of
      the monomeric portal protein of bacteriophage P22: implications for portal
      assembly.
AB  - The head of the P22 bacteriophage is interrupted by a unique dodecameric portal
      vertex that serves as a conduit for the entrance and exit of the DNA. Here, the
      in vitro unfolding/refolding processes of the portal protein of P22 were
      investigated at different temperatures (1, 25, and 37 degrees C) through the use
      of urea and high hydrostatic pressure (HHP) combined with spectroscopic
      techniques. We have characterized an intermediate species, IU, which forms at 25
      degrees C during unfolding or refolding of the portal protein in 2-4 M urea. IU
      readily forms amorphous aggregates, rendering the folding process irreversible.
      On the other hand, at 1 degrees C, a two-state process is observed (DeltaGf = 
      2.2 kcal/mol). When subjected to HHP at 25 or 37 degrees C, the portal monomer
      undergoes partial denaturation, also forming an intermediate species, which we
      call IP. IP also tends to aggregate but, differently from IU, aggregates into a
      ring-like structure as seen by size-exclusion chromatography and electron
      microscopy. Again, at 1 degrees C the unfolding induced by HHP proved to be
      reversible, with DeltaGf = -2.4 kcal/mol and DeltaV = 72 mL/mol. Interestingly,
      at 25 degrees C, the binding of the hydrophobic probe bis-ANS to the native
      portal protein destabilizes it and completely blocks its aggregation under HHP.
      These data are relevant to the process by which the portal protein assembles into
      dodecamers in vivo, since species such as IP must prevail over IU in order to
      guarantee the proper ring formation.

PMID- 17542561
TI  - Quantum-chemical investigation of the structures and electronic spectra of the
      nucleic acid bases at the coupled cluster CC2 level.
AB  - We study the ground-state structures and singlet- and triplet-excited states of
      the nucleic acid bases by applying the coupled cluster model CC2 in combination
      with a resolution-of-the-identity approximation for electron interaction
      integrals. Both basis set effects and the influence of dynamic electron
      correlation on the molecular structures are elucidated; the latter by comparing
      CC2 with Hartree-Fock and Moller-Plesset perturbation theory to second order.
      Furthermore, we investigate basis set and electron correlation effects on the
      vertical excitation energies and compare our highest-level results with
      experiment and other theoretical approaches. It is shown that small basis sets
      are insufficient for obtaining accurate results for excited states of these
      molecules and that the CC2 approach to dynamic electron correlation is a reliable
      and efficient tool for electronic structure calculations on medium-sized
      molecules.

PMID- 17542562
TI  - Investigation of the electronic spectra and excited-state geometries of poly(para
      phenylene vinylene) (PPV) and poly(para-phenylene) (PP) by the symmetry-adapted
      cluster configuration interaction (SAC-CI) method.
AB  - The symmetry-adapted cluster-configuration interaction (SAC-CI) method has been
      used to investigate the optical and geometric properties of the oligomers of
      poly(para-phenylene vinylene) (PPV) and poly(para-phenylene) (PP). Vertical
      singlet and triplet absorption spectra and emission spectra have been calculated
      accurately; the mean average deviation from available experimental results lies
      within 0.2 eV. The chain length dependence of the transition energies has been
      improved in comparison to earlier TDDFT and MRSDCI calculations. The present
      analysis suggests that conventional TDDFT with the B3LYP functional should be
      used carefully, as it can provide inaccurate estimates of the chain length
      dependence of the excitation energies of these molecules with long pi
      conjugation. The T1 state was predicted to be at a lower energy, by 1.0-1.5 eV
      for PPV and by 0.9-1.7 eV for PP, than the S1 state, which indicates a localized
      T1 state with large exchange energy. By calculating the SAC-CI electron density
      difference between the ground and excited states, the geometry relaxations due to
      excitations can be analyzed in detail using electrostatic force theory. For trans
      stilbene, the doubly excited 21Ag state was studied, and the calculated
      transition energy of 4.99 eV agrees very well with the experimental value of 4.84
      eV. In contrast to previous ab initio calculations, we predict this doubly
      excited 21Ag state to lie above the 11Bu state.

PMID- 17542563
TI  - Overtone spectroscopy of sulfonic acid derivatives.
AB  - Vapor-phase OH-stretching overtone spectra of methanesulfonic acid and
      trifluoromethanesulfonic acid were recorded in the Deltav(OH) = 4 and 5 regions
      using cavity ring-down spectroscopy. We compare these spectra to those of
      sulfuric acid to consider the effect on vibrational overtone spectra of replacing
      one of the OH groups with a more or less electronegative group. We complement our
      experimental work with anharmonic oscillator local mode calculations of the OH
      stretching frequencies and intensities. The presence of a weak intramolecular
      interaction between the hydrogen atom of the OH group and the oxygen atom of the
      adjacent S=O group in methanesulfonic acid lowers its OH-stretching frequency
      from what would otherwise be predicted based on the electronegativity of the
      methyl group.

PMID- 17542564
TI  - A remeasurement of the products for electron recombination of N2H+ using a new
      technique: no significant NH+N production.
AB  - A remeasurement of the product distribution from dissociative electron-ion
      recombination (DR) of N2H+ has been made using a new technique. The technique
      employs electron impact to ionize the neutral products prior to detection by a
      quadrupole mass analyzer. Two experimental approaches, both using pulsed gas
      techniques, isolate and quantify the DR products. In one approach, an electron
      attaching gas is pulsed into a flowing afterglow to transiently quench DR.
      Results from this approach give an upper limit of 5% for the NH+N product
      channel. In the second approach, the reagent gas N2 is pulsed. The absolute
      percentages of products were monitored versus initial N2 concentration. Results
      from this approach also give an upper limit of 5% for NH+N production. This
      establishes that N2+H is the dominant channel, being at least between 95 and
      100%, and that there is no significant NH production contrary to a recent storage
      ring measurement that yielded 64% NH+N and 36% N2+H. Possible reasons for this
      dramatic difference are discussed.

PMID- 17542565
TI  - Oxygenated interface on biomass burn tar balls determined by single particle
      scanning transmission X-ray microscopy.
AB  - Carbonaceous particles originating from biomass burning can account for a large
      fraction of organic aerosols in a local environment. Presently, their
      composition, physical and chemical properties, as well as their environmental
      effects are largely unknown. Tar balls, a distinct type of highly spherical
      carbonaceous biomass burn particles, have been observed in a number of field
      campaigns. The Yosemite Aerosol Characterization Study that took place in summer
      2002 occurred during an active fire season in the western United States; tar
      balls collected during this field campaign are described in this article.
      Scanning transmission X-ray microscopy and near-edge X-ray absorption fine
      structure spectroscopy are used to determine the shape, structure, and size
      dependent chemical composition of approximately 150 individual spherical
      particles ranging in size from 0.15 to 1.2 mum. The elemental composition of tar
      balls is approximately 55% atomic carbon and approximately 45% atomic oxygen.
      Oxygen is present primarily as carboxylic carbonyls and oxygen-substituted alkyl
      (O-alkyl-C) functional groups, followed by moderate amounts of ketonic carbonyls.
      The observed chemical composition, density, and carbon functional groups are
      distinctly different from soot or black carbon and more closely resemble high
      molecular weight polymeric humic-like substances, which could account for their
      reported optical properties. A detailed examination of the carboxylic carbonyl
      and O-alkyl-C functional groups as a function of particle size reveals a thin
      oxygenated interface layer. The high oxygen content, as well as the presence of
      water-soluble carboxylic carbonyl groups, could account for the reported
      hygroscopic properties of tar balls. The presence of the oxygenated layer is
      attributed to atmospheric processing of biomass burn particles.

PMID- 17542566
TI  - The hydrogen molecule in strong magnetic fields: optimizations of anisotropic
      Gaussian basis sets.
AB  - The anisotropic Gaussian basis sets were optimized for the H atom and the
      hydrogen molecule in strong magnetic fields of 0-1000 a.u. We used five-parameter
      fit functions to generate anisotropic Gaussian exponents of hydrogenic atomic
      orbitals. These functions provided errors of energy that were comparable to the
      independent optimization of all the exponents. The optimal exponents were used to
      calculate the Hartree-Fock energies of H2 at arbitrary orientations, with respect
      to the magnetic field. Furthermore, the double-exponential transformation was
      applied to calculate highly anisotropic Coulomb integrals. Between magnetic field
      strengths of 1 a.u. and 100 a.u., a molecule in a triplet ground state
      continuously changed its stable orientation from the perpendicular geometry to
      the parallel geometry.

PMID- 17542567
TI  - Imaging the state-specific vibrational predissociation of the C2H2-NH3 hydrogen
      bonded dimer.
AB  - The state-to-state vibrational predissociation (VP) dynamics of the hydrogen
      bonded ammonia-acetylene dimer were studied following excitation in the
      asymmetric CH stretch. Velocity map imaging (VMI) and resonance-enhanced
      multiphoton ionization (REMPI) were used to determine pair-correlated product
      energy distributions. Following vibrational excitation of the asymmetric CH
      stretch fundamental, ammonia fragments were detected by 2 + 1 REMPI via the B1E''
      <-- X1A1' and C'1A1' <-- X1A1' transitions. The fragments' center-of-mass (c.m.)
      translational energy distributions were determined from images of selected
      rotational levels of ammonia with one or two quanta in the symmetric bend (nu2
      umbrella mode) and were converted to rotational-state distributions of the
      acetylene co-fragment. The latter is always generated with one or two quanta of
      bending excitation. All the distributions could be fit well when using a dimer
      dissociation energy of D0 = 900 +/- 10 cm(-1). Only channels with maximum
      translational energy <150 cm(-1) are observed. The rotational excitation in the
      ammonia fragments is modest and can be fit by temperatures of 150 +/- 50 and 50
      +/- 20 K for 1nu2 and 2nu2, respectively. The rotational distributions in the
      acetylene co-fragment pair-correlated with specific rovibrational states of
      ammonia appear statistical as well. The vibrational-state distributions, however,
      show distinct state specificity among channels with low translational energy
      release. The predominant channel is NH3(1nu2) + C2H2(2nu4 or 1nu4 + 1nu5), where
      nu4 and nu5 are the trans- and cis-bend vibrations of acetylene, respectively. A
      second observed channel, with much lower population, is NH3(2nu2) + C2H2(1nu4).
      No products are generated in which the ammonia is in the vibrational ground state
      or the asymmetric bend (1nu4) state, nor is acetylene ever generated in the
      ground vibrational state or with CC stretch excitation. The angular momentum (AM)
      model of McCaffery and Marsh is used to estimate impact parameters in the
      internal collisions that give rise to the observed rotational distributions.
      These calculations show that dissociation takes place from bent geometries, which
      can also explain the propensity to excite fragment bending levels. The low recoil
      velocities associated with the observed channels facilitate energy exchange in
      the exit channel, which results in statistical-like fragment rotational
      distributions.

PMID- 17542568
TI  - Resonance Raman de-enhancement caused by excited state mixed valence.
AB  - Resonance Raman and absorption spectra of 9,10-bis(2-tert-butyl-2,3
      diazabicyclo[2.2.2]oct-3-yl)-anthracene (2) are measured and analyzed. The
      contribution of the individual vibrational normal modes to the reorganization
      energy is investigated. Excited-state mixed valence in this system is analyzed
      using density functional theory electronic structure calculations. The resonance
      Raman excitation profiles exhibit a resonance de-enhancement effect around 20 725
      cm-1, but a corresponding feature is not observed in the absorption spectrum.
      This unusual observation is attributed to the presence of a dipole-forbidden,
      vibronically allowed component of the split mixed valence excited state. The de
      enhancement dip is calculated quantitatively and explained in terms of the real
      and imaginary components of the polarizabilities of the two overlapping excited
      states.

PMID- 17542569
TI  - Measurements and quasi-quantum modeling of the steric asymmetry and parity
      propensities in state-to-state rotationally inelastic scattering of NO (2Pi1/2)
      with D2.
AB  - Relative integrated cross sections are measured for spin-orbit-conserving,
      rotationally inelastic scattering of NO (2Pi1/2), hexapole-selected in the upper
      Lambda-doublet level of the ground rotational state (j = 0.5), in collisions with
      D2 at a nominal energy of 551 cm-1. The final state of the NO molecule is
      detected by laser-induced fluorescence (LIF). The state-selected NO molecule is
      oriented with either the N end or the O end toward the incoming D2 molecule by
      application of a static electric field E in the scattering region. This field is
      directed parallel or antiparallel to the relative velocity vector v. Comparison
      of signals taken for the different applied field directions gives the
      experimental steric asymmetry SA, defined by SA = (sigma v upward arrow downward
      arrow E - sigma v upward arrow upward arrow E)/(sigma v upward arrow downward
      arrow E + sigma v upward arrow upward arrow E), which is equal to within a factor
      of -1 to the molecular steric effect, Si-->f identical with (sigmaD2-->NO -
      sigmaD2-->ON)/(sigmaD2-->NO + sigmaD2-->ON). The dependence of the integral
      inelastic cross section on the incoming Lambda-doublet component is also measured
      as a function of the final rotational (jfinal) and Lambda-doublet (epsilonfinal)
      state. The measured steric asymmetries are similar to those previously observed
      for NO-He scattering. Spin-orbit manifold-conserving collisions exhibit a larger
      propensity for parity conservation than their NO-He counterparts. The results are
      interpreted in the context of the recently developed quasi-quantum treatment
      (QQT) of rotationally inelastic scattering [Gijsbertsen, A.; Linnartz, H.;
      Taatjes, C. A.; Stolte, S. J. Am. Chem. Soc. 2006, 128, 8777]. The QQT
      predictions can be inverted to obtain a fitted hard-shell potential that
      reproduces the experimental steric asymmetry; this fitted potential gives an
      empirical estimate of the anisotropy of the repulsive interaction between NO and
      D2. QQT computation of the differential cross section using this simple model
      potential shows reasonable agreement with the measured differential cross
      sections.

PMID- 17542570
TI  - Accurate evaluation of valence and low-lying Rydberg states with standard time
      dependent density functional theory.
AB  - Using a standard exchange-correlation functional, namely, PBE0, the basis set
      dependence of time-dependent density functional theory (TD-DFT) calculations has
      been explored using 33 different bases and five organic molecules as test cases.
      The results obtained show that this functional can provide accurate (i.e., at
      convergence) results for both valence and low-lying Rydberg excitations if at
      least one diffuse function for the heavy atoms is included in the basis set.
      Furthermore, these results are in fairly good agreement with the experimental
      data and with those delivered by other functionals specifically designed to yield
      correct asymptotic/long-range behavior. More generally, the PBE0 calculations
      show that a greater accuracy can be obtained for both Rydberg and valence
      excitations if they occur at energies below the epsilonHOMO + 1 eV threshold.
      This latter value is proposed as a thumb rule to verify the accuracy of TD
      DFT/PBE0 applications.

PMID- 17542571
TI  - Pyridazinoquinolinetriones as NMDA glycine-site antagonists with oral
      antinociceptive activity in a model of neuropathic pain.
AB  - A series of 7-chloro-2,3-dihydro-2-[1-(pyridinyl)alkyl]-pyridazino[4,5
      b]quinoline-1,4,10(5H)-triones were synthesized and found to have potent activity
      at the glycine site of the NMDA receptor. In some cases, these compounds
      possessed poor aqueous solubility that may have contributed to poor rat oral
      bioavailability. Subsequently, compounds have been identified with improved
      aqueous solubility and oral bioavailability. Several of these compounds were
      examined in a rat chronic constrictive injury (CCI) model of neuropathic pain and
      found to have potent activity when dosed orally.

PMID- 17542572
TI  - Total synthesis and biological evaluation of C16 analogs of (-)-dictyostatin.
AB  - The structure-activity relationship of the crucial C16 region of (-)-dictyostatin
      was established through total synthesis of analogs followed by detailed
      biological characterization. A versatile synthetic strategy was used to prepare
      milligram quantities of 16-normethyldictyostatin, 16-epi-dictyostatin, and the
      C16-normethyl-C15Z isomer. Along the way, a number of other E/Z isomers and
      epimers were prepared, and a novel lactone ring contraction to make iso
      dictyostatins with 20-membered macrolactones (instead of 22-membered
      macrolactones) was discovered. The synthesis of 16-normethyl-15,16
      dehydrodictyostatin is the first of any dictyostatin by a maximally convergent
      route in which three main fragments are assembled, coupled in back-to-back steps,
      and then processed through refunctionalization and macrolactonization. Cell-based
      and biochemical evaluations showed 16-normethyl-15,16-dehydrodictyostatin and 16
      normethyldictyostatin to be the most potent of the new agents, only 2- and 5-fold
      less active than (-)-dictyostatin itself. This data and that from previously
      generated dictyostatin analogs are combined to produce a picture of the structure
      activity relationships in this series of anticancer agents.

PMID- 17542573
TI  - Synthesis and preliminary biological characterization of new semisynthetic
      derivatives of ramoplanin.
AB  - Ramoplanin is a glycolipodepsipeptide antibiotic active against Gram-positive
      bacteria including vancomycin-resistant enterococci. Ramoplanin inhibits
      bacterial cell wall biosynthesis by a mechanism different from that of
      glycopeptides and hence does not show cross-resistance with these antibiotics.
      The systemic use of ramoplanin has been so far prevented because of its low local
      tolerability when injected intravenously. To overcome this problem, the fatty
      acid side chain of ramoplanin was selectively removed and replaced with a variety
      of different carboxylic acids. Many of the new ramoplanin derivatives showed
      antimicrobial activity similar to that of the natural precursor coupled with a
      significantly improved local tolerability. Among them the derivative in which the
      2-methylphenylacetic acid has replaced the di-unsaturated fatty acid side chain
      (48) was selected as the most interesting compound and submitted to further in
      vitro and in vivo characterization studies.

PMID- 17542574
TI  - C-3 alkyl/arylalkyl-2,3-dideoxy hex-2-enopyranosides as antitubercular agents:
      synthesis, biological evaluation, and QSAR study.
AB  - A series of C-3 alkyl and arylalkyl 2,3-dideoxy hex-2-enopyranoside derivatives
      were synthesized by Morita-Baylis-Hillman reaction using enulosides 4, 5, and 6
      and various aliphatic and aromatic aldehydes. The compounds were evaluated in
      vitro for the complete inhibition of growth of Mycobacterium tuberculosis H37Rv.
      They exhibited moderate to good activity in the range of 25-1.56 mug/mL. Among
      these, 4d, 4h, 5c, and 4hr showed activity at minimum inhibitory concentrations,
      3.12, 6.25, 1.56, and 1.56 mug/mL, respectively. These compounds were safe
      against cytotoxicity in VERO cell line and mouse macrophage cell line J 744A.1. A
      QSAR analysis by CP-MLR with alignment-free 3D-descriptors indicated the
      relevance of structure space comparable to the minimum energy conformation (from
      conformational analysis) of 5c to the activity. The study indicates that the
      compounds attaining the conformational space of 5c and reflecting some symmetry,
      minimum eccentricity, and closely placed geometric and electronegativity centers
      therein are favorable for activity.

PMID- 17542575
TI  - Structure determination of novel orthoborate NaMgBO(3): a promising birefringent
      crystal.
AB  - A novel orthoborate, NaMgBO(3), has been successfully synthesized by a standard
      solid-state reaction, and the crystal structure has been determined from powder X
      ray diffraction data. It crystallizes in the monoclinic space group C2/c with
      lattice parameters a = 5.01313(6) Angstrom, b = 8.8007(1) Angstrom, c =
      5.52831(7) Angstrom, and beta = 99.6962(6) degrees. Isolated [BO(3)](3-) anionic
      groups, which are the fundamental building units, are distributed perfectly
      parallel to each other. It is a typical structure of big birefringent crystals.
      The overall structure is similar to that of NaSrBO(3), which crystallizes in
      P2(1)/c. The correlation between these two structures is discussed. The Mg atoms
      in NaMgBO(3) are used instead of the position of Na in NaSrBO(3), while the Na
      atoms occupy the position of Sr. Then the directions of the BO(3) triangles are
      changed to balance the bond valence, which leads to a higher symmetry. They are
      the first pair of alkali-alkaline earth orthoborates with close space groups by
      exchange of the cation positions.

PMID- 17542576
TI  - Rare-Earth complexes of ferrocene-containing ligands: visible-light excitable
      luminescent materials.
AB  - The ferrocene-derivatives bis(ferrocenyl-ethynyl)-1,10-phenanthroline (Fc(2)phen)
      and ferrocenoyltrifluoroacetone (Hfta) have been used to synthesize ferrocene
      containing rare-earth beta-diketonate complexes. The complexes
      [Ln(tta)(3)(Fc(2)phen)] and [Ln(fta)(3)(phen)] (where Ln = La, Nd, Eu, Yb) show
      structural similarities to the tris(2-thenoyltrifluoroacetonate)(1,10
      phenanthroline)lanthanide(III) complexes, [Ln(tta)(3)(phen)]. The coordination
      number of the lanthanide ion is 8, and the coordination sphere can be described
      as a distorted dodecahedron. However, the presence of the ferrocene moieties
      shifts the ligand absorption bands of the rare-earth complexes to longer
      wavelengths so that the complexes can be excited not only by ultraviolet
      radiation but also by visible light of wavelengths up to 420 nm. Red
      photoluminescence is observed for the europium(III) complexes and near-infrared
      photoluminescence for the neodymium(III) and ytterbium(III) complexes. The
      presence of the ferrocene groups makes the rare-earth complexes hydrophobic and
      well-soluble in apolar organic solvents.

PMID- 17542577
TI  - Synthesis and properties of a cationic bidentate Lewis acid.
AB  - As part of our efforts to increase the fluoride affinity of bidentate Lewis
      acids, we have set out to determine if the F(-) anion chelation occurring in such
      systems can be complemented by favorable Coulombic attractions. To explore this
      idea, the neutral B/Hg bidentate Lewis acid 1-{Mes(2)B}-8-{(2,6-Me(2)-4
      Me(2)NC(6)H(2))Hg}C(10)H(6) (3) and its cationic analogue [1-{Mes(2)B}-8-{(2,6
      Me2-4-Me(3)NC(6)H(2))Hg}C(10)H(6)]+ ([4]+) have been synthesized and studied.
      Compound 3 as well as the triflate salt of [4]+ react with
      [S(NMe(2))3][Me(3)SiF(2)] to afford the corresponding fluoride complexes [3
      micro(2)-F]- and [4-micro(2)-F]. Spectroscopic and structural studies confirm
      that the F- anion bridges the two Lewis acidic centers in both [3-micro(2)-F]-
      and [4-micro(2)-F]. UV-vis titration experiments carried out in
      tetrahydrofuran/water (9/1, v/v) mixtures indicate that the fluoride binding
      constants of 3 and [4]+ are clearly differentiated and are equal to 1.3 (+/-0.1)
      x 10(2) M(-1) and 6.2 (+/-0.2) x 10(4) M(-1), respectively. The enhanced fluoride
      binding constant of [4]+, when compared to 3, confirms that the chelate effect
      occurring in these types of fluoride receptors can be combined with favorable
      Coulombic attractions to strengthen the host-guest interaction. Cation [4]+
      remains highly selective for F- over other environmentally abundant anions
      including Cl-, Br-, NO(3)(-), H(2)PO(4)(-), and HSO(4)(-) and shows only a weak
      response to OAc(-). Finally, the addition of an aqueous solution of Al3+ to a
      solution containing [4-micro(2)-F] leads to complete regeneration of [4]+,
      showing that F(-) binding is reversible.

PMID- 17542578
TI  - Use of calix[4]arenes in the redox chemistry of lanthanides: the reduction of
      dinitrogen by a calix[4]arene-samarium complex.
AB  - The synthesis and structural characterization of a samarium-dinitrogen complex
      supported by a calix[4]arene ligand in which the N-N bond distance has been
      stretched to 1.611(16) Angstrom are described. The central mu(3)
      eta(2):eta(2):eta(2)-hydrazido tetraanion formed is bonded to three Sm(III)
      centers with an overall butterfly-type arrangement.

PMID- 17542579
TI  - Reduction energy of 1 M aqueous ruthenium(III) hexaammine in the gas phase: a
      route toward establishing an absolute electrochemical scale.

PMID- 17542580
TI  - A time-resolved electron paramagnetic resonance investigation of the spin
      exchange and chemical interactions of reactive free radicals with isotopically
      symmetric (14N-X-14N) and isotopically asymmetric (14N-X-15N) nitroxyl
      biradicals.
AB  - Interactions between reactive free radicals (r) with stable mononitroxyl radicals
      (N) and bisnitroxyl radicals (N-X-N) were studied by time-resolved electron
      paramagnetic resonance (TR-EPR). Reactive spin-polarized free radicals (r#), with
      non-Boltzmann population of spin states were produced by laser flash photolysis
      of benzil dimethyl monoketal or of (2,4,6-trimethylbenzoyl)diphenyl phosphine
      oxide (the superscript # symbol indicates electron spin polarization). Both
      isotopically symmetric nitroxyl biradicals (14N-X-14N) and isotopically
      asymmetric nitroxyl biradicals, with one nitroxyl bearing 15N and the other
      nitroxyl bearing 14N (14N-X-15N), were employed as probes of the spin exchange
      and chemical interactions between r and the nitroxyl biradicals. The interaction
      of r# with the asymmetric ortho-nitroxyl biradical (14N-O-15N), which exists in a
      condition of strong spin exchange, proved to be particularly informative. In this
      case, spin polarized (14N-O-15N)# (product of spin exchange with r#) and two
      polarized monoradicals (r14N-O-15N)# and (14N-O-15Nr)# (products of chemical
      reaction with r#) were observed. The latter three species possess three distinct
      TR-EPR spectra with different line splittings. The relative cross sections for
      spin exchange (Rex) and chemical reaction (Rrxn) were achieved through computer
      simulation of the TR-EPR spectra. The cross section for spin exchange, Rex,
      between r# and (N-X-N) biradical is estimated to be 4-6 times larger than the
      cross section of chemical reaction, Rrxn, between r# and (N-X-N). The para
      nitroxyl biradical (14N-P-15N) exists in weak spin exchange, and behaves as an
      equimolar mixture of 14N and 15N mononitroxyls.

PMID- 17542581
TI  - Prototype protein assembly as scaffold for time-resolved fluoroimmuno assays.
AB  - Turnip yellow mosaic virus (TYMV) is an icosahedral plant virus with an average
      diameter of 28 nm and can be isolated in gram quantities from turnip or Chinese
      cabbage inexpensively. In this study, it was selected as a prototype
      bionanoparticle for time-resolved fluoroimmuno assay (TRFIA). Two types of
      reactive amino acid residues were employed to anchor luminescent terbium
      complexes and biotin groups based on orthogonal chemical reactions. While terbium
      complexes were used as luminescent signaling groups, biotin motifs acted as a
      model ligand for protein binding. The bioconjugation results were confirmed by MS
      and Western blot analysis. Steady-state and time-resolved luminescence study of
      the dual-modified viruses demonstrated that the spectroscopic properties of the
      Tb complex are unperturbed by the labeling procedure. The dual-modified particle
      was probed by fluorescence resonance energy transfer (FRET) experiments using
      avidin labeled with an Alexa488 fluorophore, which bound to the biotin on the
      surface of the particle, as an energy acceptor, and terbium complexes as an
      energy donor. The emission and excitation spectra of the dual-labeled TYMV
      particle displayed residual virus fluorescence and Tb luminescence upon ligand
      centered excitation. The Tb luminescence lifetime was 1.62 ms and could be
      effectively fitted with a single-exponential behavior. In the TRFIA, an efficient
      transfer of 66% was observed, and the calculation using the Forster radius of 41
      A allowed for an estimation of the average donor-acceptor distance of 36 A. Our
      studies show that the two reactive sites can communicate with each other on the
      surface of a nanoscale biological assembly. In particular, the ligand-receptor
      binding (biotin and avidin in this paper) was not interfered with when anchored
      to the surface of TYMV. Therefore, as a prototype of polyvalent bionanoparticles,
      TYMV can be used as scaffold for sensor development with TRFIA.

PMID- 17542583
TI  - Mechanism of activation of a hafnium pyridyl-amide olefin polymerization
      catalyst: ligand modification by monomer.
AB  - We have investigated the olefin polymerization mechanism of hafnium catalysts
      supported by a pyridyl-amide ligand with an ortho-metalated naphthyl group.
      Ethylene-alpha-olefin copolymers from these catalysts have broad molecular weight
      distributions that can be fit to a bimodal distribution. We propose a unique
      mechanism to explain this behavior involving monomer modification of the
      catalyst, which generates multiple catalyst species when multiple monomers are
      present. More specifically, we present evidence that the hafnium alkyl cation
      initially undergoes monomer insertion into the Hf-naphthyl bond, which
      permanently modifies the ligand to generate new highly active olefin
      polymerization catalysts. Under ethylene/octene copolymerization conditions, a
      plurality of new catalysts is formed in relative proportion to the respective
      monomer concentrations. Due to the asymmetry of the metal complex, two "ethylene
      inserted" and eight "octene-inserted" isomers are possible, but it is a useful
      approximation to consider only one of each in the polymerization behavior.
      Consequently, gel permeation chromatography data for the polymers can be fit to a
      bimodal distribution having a continuous shift from a predominantly low molecular
      weight fraction to predominantly higher molecular weight fraction as
      [octene]/[ethylene] is increased. Theoretical calculations show that such
      insertions into the Hf-aryl bond have lower barriers than corresponding
      insertions into the Hf-alkyl bond. The driving forces for this insertion into the
      Hf-aryl bond include elimination of an eclipsing H-H interaction and formation of
      a stabilizing Hf-arene interaction. These new "monomer-inserted catalysts" have
      no beta-agostic interaction, very weak olefin binding, and olefin-insertion
      transition states which differ on the two sides by more than 4 kcal/mol. Thus,
      the barrier to site epimerization is very low and high polymerization rates are
      possible even when the chain wags prior to every insertion. Experimental evidence
      for aryl-insertion products is obtained from reactions of ethylene (13C2H4 NMR
      studies) or 4-methyl-1-pentene (4M1P) using relatively low monomer/catalyst
      ratios. Quantitative generation of monomer-inserted products is complicated by
      slow initiation kinetics followed by fast polymerization kinetics. However, NMR
      evidence for reaction with 13C2H4 was observed in situ at low temperature, and
      the attachment of monomer to ligand was confirmed by GC/MS and 13C NMR after
      quenching. Furthermore, a 4M1P-appended ligand was isolated from a polymerization
      reaction (50:1 monomer:catalyst) by column chromatography followed by multiple
      recrystallizations. One isomer was characterized by X-ray crystallography, which
      unequivocally shows a 4-methylpentyl substituent at the 2-position of the
      naphthyl, consistent with 1,2-insertion into the Hf-aryl bond. NMR suggests a
      second diastereomer (not isolated) is formed from a 1,2-insertion of opposite
      stereoselectivity.

PMID- 17542582
TI  - Luminescent silica nanobeads: characterization and evaluation as efficient
      cytoplasmatic transporters for T-lymphocytes.
AB  - We report the fabrication and characterization of neutravidin-conjugated silica
      nanobeads doped with a ruthenium-complex luminophore and functionalized with
      antihuman CD3, antihuman CD28, and an acid-sensitive polymer. We observed that
      the nanobeads were readily delivered into Jurkat T leukemia cells by endocytosis,
      transported into lysosomes and subsequently into the cytoplasm as revealed by pH
      sensitive luminescence. Since signs of cytotoxicity were not observed, the
      reported nanobeads could be an excellent and nontoxic building block for
      efficient intracellular transporters.

PMID- 17542584
TI  - An alternating pi-stacked bisdithiazolyl radical conductor.
AB  - A general synthetic route to the resonance-stabilized pyrazine-bridged
      bisdithiazolyl framework, involving the reductive deprotection of 2,6
      diaminopyrazine-bisthiocyanate and cyclization with thionyl chloride, has been
      developed. An N-methyl bisdithiazolyl radical, 4-methyl-4H
      bis[1,2,3]dithiazolo[4,5-b:5',4'-e]pyrazin-3-yl, has been prepared and
      characterized in solution by electron paramagnetic resonance spectroscopy and
      cyclic voltammetry. Its crystal structure has been determined at several
      temperatures. At 295 K, the structure belongs to the space group Cmca and
      consists of evenly spaced radicals pi-stacked in an alternating ABABAB fashion
      along the x-direction. At 123 K, the space group symmetry is lowered by loss of C
      centering to Pccn, so that the radicals are no longer evenly spaced along the pi
      stack. At 88 K, a further lowering of space group symmetry to P21/c is observed.
      Extended Huckel Theory band structure calculations indicate a progressive opening
      of a band gap at the Fermi level in the low-temperature structures. Magnetic
      susceptibility measurements over the range 4-300 K reveal essentially diamagnetic
      behavior below 120 K. Variable-temperature single-crystal conductivity (sigma)
      measurements indicate that the conductivity is activated, even at room
      temperature, with a room-temperature value sigma RT=0.001 S cm-1 and a thermal
      activation energy Eact=0.19 eV. Under an applied pressure of 5 GPa, sigma RT is
      increased by 3 orders of magnitude, but the conductivity remains activated, with
      Eact being lowered to 0.11 eV at 5.5 GPa.

PMID- 17542585
TI  - Transposing molecular fluorescent switches into the near-IR: development of
      luminogenic reporter substrates for redox metabolism.

PMID- 17542586
TI  - Regioselective and enantioselective iridium-catalyzed allylation of enamines.

PMID- 17542587
TI  - Monomeric and heterodimeric triple helical DNA mimics.
AB  - The construction of artificial triple helical structures with oligonucleotides
      containing non-nucleosidic phenanthrenes and pyrenes is described. The
      polyaromatic building blocks, which are used as connectors between the Hoogsteen
      strand and the Watson-Crick hairpin, lead to a significant stabilization of
      intramolecular triple helices. Description of the relative orientation of pyrene
      building blocks is rendered possible by the observation of exciton coupling in
      the circular dichroism spectra. In addition, the formation of heterodimeric
      triple helical constructs is explored. Again, the polyaromatic residues are found
      to have a positive effect on the stability of these structures. The results are
      important for the design and construction of nucleic-acid-based, triple helical
      architectures. Furthermore, they will help in the development of analogues of
      biologically important, naturally occurring triplex structures.

PMID- 17542588
TI  - Olefin metathesis reactions with vinyl halides: formation, observation,
      interception, and fate of the ruthenium-monohalomethylidene moiety.

PMID- 17542589
TI  - Functionalization of single-walled carbon nanotubes and fullerenes via a dimethyl
      acetylenedicarboxylate-4-dimethylaminopyridine zwitterion approach.

PMID- 17542590
TI  - Exploiting ligand conformation in selective inhibition of non-ribosomal peptide
      synthetase amino acid adenylation with designed macrocyclic small molecules.

PMID- 17542591
TI  - Lewis acid acceleration of C-N bond-forming reductive elimination from
      heteroarylpalladium complexes and catalytic amidation of heteroaryl bromides.

PMID- 17542592
TI  - Reactivity of a disilyne RSi identical with SiR (R=SiiPr[CH(SiMe3)2]2) toward pi
      bonds: stereospecific addition and a new route to an isolable 1,2-disilabenzene.

PMID- 17542594
TI  - Development of a catalytic aromatic decarboxylation reaction.
AB  - A palladium-catalyzed aromatic decarboxylation reaction has been developed. With
      electron-rich aromatic acids, the reaction proceeds efficiently under fairly mild
      conditions in good yields. The method was useful with complex functionalized
      substrates containing hindered carboxylic acids.

PMID- 17542595
TI  - Photoinduced diastereoselective addition of perfluoroalkyl iodides to acrylic
      acid derivatives for the synthesis of fluorinated amino acids.
AB  - Photoinduced diastereoselective addition of perfluoroalkyl iodides in the
      presence of an aqueous solution of Na2S2O3 was an excellent method for
      iodoperfluoroalkylation of acrylic acid derivatives bearing a chiral auxiliary,
      with moderate to good stereoselectivities and with no detectable side products.
      The iodoperfluoroalkylation of N-acyloylcamphorsultam provided a convenient route
      for preparing chiral fluorine-containing amino acids.

PMID- 17542596
TI  - A tightly coupled bis(zinc(II) phthalocyanine)-perylenediimide ensemble to yield
      long-lived radical ion pair states.
AB  - A conjugated donor-acceptor array composed of two phthalocyanines connected to
      the bay region of a perylenediimide is assembled by using palladium chemistry.
      Excitation of the phthalocyanine produces a nanosecond lived charge-separated
      state.

PMID- 17542597
TI  - A stereoselective entry into functionalized 1,2-diamines by zinc-mediated
      homologation of alpha-aminoacids.
AB  - A general, stereoselective synthesis of 4,5-disubstituted imidazolidines-2-ones
      from alpha-aminoacids has been developed: the key steps are a Blaise reaction of
      bromoacetate on alpha-aminonitriles and further reduction. Although reduction
      with sodium cyanoborohydride afforded a mixture of cis and trans isomers 6a-e
      with moderate to good stereoselectivity, reduction with sodium in liquid ammonia
      gave the trans isomers 8a-e with complete stereoselectivity. Acidic hydrolysis of
      the urea gave 4-amino-pyrrolidinones, which can be precursors to beta,gamma
      diaminoacids or 3-aminopyrrolidines.

PMID- 17542598
TI  - Decoration of Au and Ag nanoparticles on self-assembling pseudopeptide-based
      nanofiber by using a short peptide as capping agent for metal nanoparticles.
AB  - The surface of a nanofiber that is formed from a self-assembling pseudopeptide
      has been decorated by gold and silver nanoparticles that are stabilized by a
      dipeptide. Transmission electron microscopic images make the decoration visible.
      In this paper, a new strategy of mineralizing a pseudopeptide based nanofiber by
      gold and silver nanoparticles with use of a two-component nanografting method is
      described.

PMID- 17542599
TI  - Soluble and easily crystallized anthracene derivatives: precursors of solution
      processable semiconducting molecules.
AB  - New soluble anthracene derivatives containing thiophene and phenylenevinylene
      derivatives were synthesized via well-known synthetic routes. TIPS derivatives
      were added at the 9,10-positions of anthracene for the solubility and
      crystallinity. Both of the molecules were found to be promising for high charge
      mobility and stable organic semiconductors. The soluble anthracene core (TIPSAnt)
      is a potential precursor for the synthesis of novel semiconducting materials.

PMID- 17542600
TI  - Reactions of dimethoxycarbene with dimethyl 2,3-dicycanomaleate and fumarate.
AB  - Dimethoxycarbene, in 2-fold or larger excess, reacts with dimethyl 2,3
      dicyanomaleate and fumarate to afford an unstable dihydrofuran 1:1 adduct that
      was shown to react further with the carbene to afford a 2:1 adduct reported
      previously. In an astonishing process, the dihydrofuran reacts with water to
      afford a mixture of (d,l and meso) dimethyl 2,3-dicyanosuccinates in which both
      hydrogen atoms of water were used to hydrogenate a C=C bond.

PMID- 17542601
TI  - Apple polyphenols affect protein kinase C activity and the onset of apoptosis in
      human colon carcinoma cells.
AB  - Polyphenol-rich apple extracts have been reported to suppress human colon cancer
      cell growth in vitro. The protein kinase C (PKC) is among the signaling elements
      known to play an important role in colon carcinogenesis. In the present study, we
      investigated whether apple polyphenols affect PKC activity and induce apoptosis
      in the human colon carcinoma cell line HT29. A polyphenol-rich apple juice
      extract (AE02) was shown to inhibit cytosolic PKC activity in a cell-free system.
      In contrast, incubation of HT29 cells for 1 or 3 h with AE02 up to 2 mg/mL did
      not affect the cytosolic PKC activity. After prolonged incubation (24 h),
      cytosolic PKC activity was modulated, albeit a u-shaped curve of effectiveness
      was observed, with an initial inhibitory effect followed by the recurrence and
      even induction of enzyme activity. Concomitantly, in the cytosol, a significant
      decrease of the protein levels of PKCalpha, PKCbetaII, and PKCgamma together with
      a significant increase of a proapoptotic PKCdelta fragment was observed. However,
      the effects on the protein levels of these PKC isoforms in the cytosol were not
      associated with translocation between the different cellular compartments but
      might instead result from the onset of apoptosis. Indeed, the treatment with AE02
      was shown to induce apoptosis by the activation of caspase-3, DNA fragmentation,
      and cleavage of poly(ADP ribose) polymerase. So far, identified and available
      constituents of the apple extract did not contribute substantially to the
      observed effects on PKC and apoptosis induction. In summary, apple polyphenols
      were found to inhibit PKC activity in a cell-free system. However, our results
      indicate that within intact cells PKC does not represent the primary target of
      apple polyphenols but appears to be affected in the course of apoptosis
      induction.

PMID- 17542602
TI  - Influence of prefermentary clarification on the composition of apple musts.
AB  - The polyphenol contents and colors of cider apple juices were compared before
      (NCM, not clarified must) and after five clarification treatments: enzymatic
      depectinization by pectinases followed by (i) sedimentation (depectinized and
      decanted juice), (ii) tangential microfiltration (microfiltered juice) or (iii)
      fining using gelatin (gelatin-treated juice); (iv) enzymatic gelification of
      pectin by pectin methylesterase followed by natural keeving by a cider
      manufacturer (producer keeved juice), or (v) flotation (floated with nitrogen gas
      juice). The pressing of the apples led to the highly selective extraction of the
      flavan-3-ols with the lowest molecular weights: In the apples, the number average
      degree of polymerization of the flavanols was 14.7, and it dropped to 2.2 in the
      NCM. Keeving had the highest impact on the reduction of both flavanol content and
      number average degree of polymerization. The flavanol concentrations were
      decreased in the permeate by fining (30%) much more than by depectinization. The
      clarification step led to a further decrease of the number average degree of
      polymerization. Hydroxycinnamic acids were less affected by the extraction
      process (with extraction yields >50%) and not affected by clarification. The
      color evolved with all treatments: L*, a*, b*, and chromaticity distance index
      measures indicated a reduction of orange-yellow saturation except after
      sedimentation.

PMID- 17542603
TI  - Colorimetric method for the estimation of total limonoid aglycones and glucoside
      contents in citrus juices.
AB  - A method for estimating the total limonoid aglycone and glucoside concentrations
      in Citrus samples in terms of limonin and limonin glucoside equivalents is
      presented. The method consists of extraction followed by colorimetric
      quantification. The colorimetric quantification was based on the formation of red
      to orange colored derivatives resulting from the treatment of limonin, limonin
      glucoside, or a fruit extract with 4-(dimethylamino)benzaldehyde (DMAB) in the
      presence of perchloric and acetic acids. Absorbance maxima for the limonin and
      limonin glucoside derivatives were found to be 470 and 503 nm, respectively. The
      influence of DMAB concentration, reaction time, and solvent composition on color
      development and sensitivity were investigated and optimal assay conditions
      established. With a microplate format under these conditions, the limits of
      detection and quantification were determined to be 0.25 and 0.50 microg/mL for
      limonin and 0.50 and 1.0 microg/mL for limonin glucoside.

PMID- 17542604
TI  - Encapsulation of lycopene extract from tomato pulp waste with gelatin and
      poly(gamma-glutamic acid) as carrier.
AB  - Tomato pulp waste, a byproduct obtained during the processing of tomato juice,
      has been shown to be a rich source of lycopene. The objectives of this study were
      to use gelatin and poly(gamma-glutamic acid) (gamma-PGA) as coating materials for
      the encapsulation of lycopene extract from tomato pulp waste. Initially, lycopene
      was extracted with supercritical carbon dioxide, followed by microencapsulation
      using an emulsion system consisting of 4.5% gelatin, 10% gamma-PGA, and 4.8%
      lycopene extract. Analysis of differential scanning calorimetry revealed that the
      thermal stability of the coating material could be up to 120 degrees C, with a
      mean particle size of 38.7 microm based on Coulter counter analysis. The total
      weight of microencapsulated powder was 617 microg with the yield of lycopene
      being 76.5%, indicating a 23.5% loss during freeze drying. During storage of
      microencapsulated powder, the concentrations of cis-, trans-, and total lycopene
      decreased along with increasing time and temperature. A fast release of lycopene
      in the powder occurred at pH 5.5 and 7.0, while no lycopene was released at pH
      2.0 and 3.5.

PMID- 17542605
TI  - Antioxidative and antiproliferative properties of selected barley (Hordeum
      vulgarae L.) cultivars and their potential for inhibition of low-density
      lipoprotein (LDL) cholesterol oxidation.
AB  - Aqueous methanolic extracts of whole kernels from six different barley cultivars,
      namely, Falcon, AC Metcalfe, Tyto, Tercel, Phoenix, and Peregrine, were examined
      for their total phenolic content (TPC), oxygen radical scavenging capacity
      (ORACFL), hydroxyl radical scavenging capacity (HORACFL), potency in prevention
      of lipid oxidation using the Rancimat method, efficacy in inhibition of Cu(II)
      induced human LDL cholesterol oxidation, and antiproliferative activities using
      Caco-2 colorectal adenocarcinoma cell line. Total phenolic content as measured by
      Folin-Ciocalteu's method ranged from 0.68 to 1.19 mg of ferulic acid equiv/g of
      defatted material, whereas ORACFL and HORACFL values were 11.28-19.10 and 9.06
      12.99 micromol of Trolox equiv/g of defatted material, respectively. Protection
      factor (PF), a measure of the effect of extracts on the prevention of oxidation
      of stripped corn oil as measured by Rancimat, ranged from 0.97 to 1.59.
      Furthermore, barley extracts showed 19.64-33.93% inhibition against Cu(II)
      induced human LDL cholesterol oxidation at a final concentration of 0.02 mg/mL.
      The proliferation of Caco-2 colon cancer cells was significantly (p < 0.05)
      inhibited in a dose-dependent fashion in the presence of all barley extracts
      tested at the end of the day 4 of incubation. At the end of day 4, barley
      extracts rendered 29.3-51.2 and 9.3-15.9% inhibition of cell proliferation at 0.5
      and 0.05 mg/mL, respectively. Phenolic extracts from whole barley kernel tested
      possessed high antioxidant, antiradical, and antiproliferative potentials.
      Therefore, inclusion of whole barley into the daily diet may render beneficial
      health benefits.

PMID- 17542606
TI  - Unfolding and refolding of beta-lactoglobulin subjected to high hydrostatic
      pressure at different pH values and temperatures and its influence on
      proteolysis.
AB  - The unfolding of beta-lactoglobulin during high-pressure treatment and its
      refolding after decompression were studied by 1H NMR and 2H/1H exchange at pH 6.8
      and 2.5 and at 37 and 25 degrees C. The extent of unfolding increased with the
      pressure level. The structure of beta-lactoglobulin required higher pressures to
      unfold at pH 2.5 than at pH 6.8. More flexibility was achieved at 37 degrees C
      than at 25 degrees C. Results indicated that the structural region formed by
      strands F, G, and H was more resistant to unfold under acidic and neutral
      conditions. The exposure of Trp19 at an earlier time, as compared to other
      protein regions, supports the formation of a swollen structural state at pH 2.5.
      Refolding was achieved faster when beta-lactoglobulin was subjected to 200 MPa
      than to 400 MPa, to 37 degrees C than to 25 degrees C, and to acidic than to
      neutral pH. After treatment at 400 MPa for 20 min at neutral pH, the protein
      native structure was not recovered. All samples at acidic pH showed that the
      protein quickly regained its structure. Hydrolysis of beta-lactoglobulin by
      pepsin and chymotrypsin could be related to pressure-induced changes in the
      structure of the protein. Compared to the behavior of the protein at atmospheric
      pressure, no increased proteolysis was found in samples with no increased
      flexibility (100 MPa, 37 degrees C, pH 2.5). Slightly flexible structures were
      associated with significantly increased proteolysis (100 MPa, 37 degrees C, pH
      6.8; 200 MPa, 37 degrees C, pH 2.5). Highly flexible structures were associated
      with very fast proteolysis (>or=200 MPa, 37 degrees C, pH 6.8; >or=300 MPa, 37
      degrees C, pH 2.5). Proteolysis of prepressurized samples improved only when the
      protein was significantly changed after the pressure treatment (400 MPa, 25
      degrees C, 20 min, pH 6.8).

PMID- 17542607
TI  - Biochemical and catalytic properties of three recombinant alcohol
      acyltransferases of melon. sulfur-containing ester formation, regulatory role of
      CoA-SH in activity, and sequence elements conferring substrate preference.
AB  - Alcohol acyltransferases (AAT) play a key role in the biosynthesis of ester aroma
      volatiles in fruit. Three ripening-specific recombinant AATs of cantaloupe
      Charentais melon fruit (Cm-AAT1, Cm-AAT3, and Cm-AAT4) are capable of
      synthesizing thioether esters with Cm-AAT1 being by far the most active. All
      proteins, as well as AAT(s) extracted from melon fruit, are active as tetramers
      of around 200 kDa. Kinetic analysis demonstrated that CoA-SH, a product of the
      reaction, is an activator at low concentrations and an inhibitor at higher
      concentrations. This was confirmed by the addition of phosphotransacetylase at
      various concentrations, capable of modulating the level of CoA-SH in the reaction
      medium. Site-directed mutagenesis of some amino acids that were specific to the
      Cm-AAT sequences into amino acids that were consensus to other characterized AATs
      greatly affected the selectivity of the original protein and the number of esters
      produced.

PMID- 17542608
TI  - Anti-inflammatory effect of alpha-linolenic acid and its mode of action through
      the inhibition of nitric oxide production and inducible nitric oxide synthase
      gene expression via NF-kappaB and mitogen-activated protein kinase pathways.
AB  - Alpha-linolenic acid (ALA) isolated from Actinidia polygama fruits exhibits
      potent anti-inflammatory activity with an unknown mechanism. To elucidate the
      molecular mechanisms of ALA on pharmacological and biochemical actions in
      inflammation, we examined the effect of ALA on lipopolysaccharide (LPS)-induced
      nitric oxide (NO) production in the murine macrophages cell line, RAW 264.7. We
      found that ALA has a strong inhibitory effect on the production of NO. ALA also
      inhibited inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and
      tumor necrosis factor-alpha (TNF-alpha) gene expressions induced by LPS. To
      explore the mechanisms associated with the inhibition of iNOS gene expression by
      ALA, we investigated its effect on LPS-induced nuclear factor-kappaB (NF-kappaB)
      activation. Treatment with ALA reduced a translocation of NF-kappaB subunit and
      NF-kappaB-dependent transcriptional activity. The activation of NF-kappaB was
      inhibited by prevention of the degradation of inhibitory factor-kappaBalpha. We
      also found that ALA inhibited LPS-induced phosphorylation of mitogen-activated
      protein kinases (MAPKs). In addition, the antinociceptive effect of ALA was also
      assessed by means of the acetic acid-induced abdominal constriction test and
      Randall-Selitto assay. ALA (5 and 10 mg/kg) showed the potent antinociceptive
      effects in these animal models. Taken together, these results suggest that ALA
      downregulates inflammatory iNOS, COX-2, and TNF-alpha gene expressions through
      the blocking of NF-kappaB and MAPKs activations in LPS-stimulated RAW 264.7
      cells, which may be the mechanistic basis for the anti-inflammatory effect of
      ALA.

PMID- 17542609
TI  - Fast and local assessment of stilbene content in grapevine leaf by in vivo
      fluorometry.
AB  - Stilbenes are grapevine phytoalexins. These highly fluorescent molecules are
      generally analyzed by HPLC. This technique allows accurate assay of different
      stilbenes, but it is destructive, time-consuming, and neglects their spatial
      distribution. This is why we have tested a new method based on in vivo
      fluorescence using commercial spectrofluorometers that allowed fast and local
      assessment of stilbene content in grapevine leaves. Stilbene synthesis in
      grapevine Vitis vinifera var. Muscat Ottonel leaves was induced by Plasmopara
      viticola inoculation or UV-C irradiation. Fluorescence was measured both from the
      abaxial and adaxial sides of leaves, then stilbene content was analyzed by HPLC.
      It varied from 0 in control leaves to 15 mg g-1 dry weight in UV-treated leaves.
      Highly significant regressions were found between HPLC stilbene content and the
      corresponding leaf UV-induced blue fluorescence. Thus, in vivo fluorescence is a
      good tool for a rapid study of stilbenes synthesis in grapevine leaves that can
      potentially be extended to other fluorescent molecules.

PMID- 17542610
TI  - Quantitative structure-antifungal activity relationships of some benzohydrazides
      against Botrytis cinerea.
AB  - Fourteen benzohydrazides have been synthesized and evaluated for their in vitro
      antifungal activity against the phytopathogenic fungus Botrytis cinerea. The best
      antifungal activity was observed for the N',N'-dibenzylbenzohydrazides 3b-d and
      for the N-aminoisoindoline-derived benzohydrazide 5. A quantitative structure
      activity relationship (QSAR) study has been developed using a topological
      substructural molecular design (TOPS-MODE) approach to interpret the antifungal
      activity of these synthetic compounds. The model described 98.3% of the
      experimental variance, with a standard deviation of 4.02. The influence of an
      ortho substituent on the conformation of the benzohydrazides was investigated by
      X-ray crystallography and supported by QSAR study. Several aspects of the
      structure-activity relationships are discussed in terms of the contribution of
      different bonds to the antifungal activity, thereby making the relationships
      between structure and biological activity more transparent.

PMID- 17542611
TI  - Use of natural and modified cyclodextrins as inhibiting agents of peach juice
      enzymatic browning.
AB  - Although cyclodextrins (CDs) have been successfully used as antibrowning agents
      in different fruit juices, no research has studied the effect of these compounds
      on enzymatic browning in peach juice. In this paper, the color of fresh peach
      juice was evaluated in the presence of two types of natural (alpha-CD and beta
      CD) and a modified (maltosyl-beta-CD) CD, and the effectiveness of these
      compounds as browning inhibitors was determined using the color space CIELAB
      system. Moreover, to clarify the mechanism by which CDs inhibit peach juice
      enzymatic browning, the process was kinetically modeled in the absence and
      presence of CDs using a colorimetric method; the apparent complexation constants
      between the mixtures of diphenols present in peach juice and some types of CD
      were calculated. The results show that the highest affinity constant was
      presented by alpha-CD (Kc = 18.31 mM-1) followed by maltosyl-beta-CD (Kc = 11.17
      mM-1), whereas beta-CD was incapable of inhibiting peach juice enzymatic
      browning. KEYWORDS: Cyclodextrin; browning; peach; juice; color; polyphenol
      oxidase.

PMID- 17542612
TI  - Anticarcinogenic activity of selenium-enriched green tea extracts in vivo.
AB  - Both selenium and green tea have been shown to have potential antitumor effects.
      Here we have investigated the anticarcinogenic effect of the selenium-enriched
      green tea extract (Se-TE) in a Kunming mice model transplanted with human
      hepatoma cells HepG2. Mice were assigned to 8 groups consisting of 10 mice each
      after tumor cell inoculation. The control group received only water, whereas the
      remaining groups received regular green tea extract (RT), Se-TE which was
      produced by fertilization with selenite on tea leaves, selenite, and RT +
      selenite. After the mice were fed intragastrically with these agents for 8 days,
      tumor growth in RT-, Se-TE-, and selenite-fed mice was significantly suppressed,
      compared with that in control mice (P < 0.001). Supplementation with Se-TEs and
      selenite was able to elevate mice blood and liver Se concentrations, but did not
      significantly enhance selenoprotein glutathione peroxidase and other antioxidant
      enzyme superoxide dismutase activity in mice blood and liver. These results
      suggest that the antitumor function of Se-TEs may be attributed to the oxidative
      stress induced by selenium and green tea components in a suitable selenium
      supplementation pathway.

PMID- 17542613
TI  - Main routes of oxygen ingress through different closures into wine bottles.
AB  - The main routes of oxygen ingress into wine bottles through "technical" cork
      stoppers (Neutrocork), natural cork stoppers, and synthetic closures (Nomacorc)
      were investigated. A comparison was made among closures left uncovered
      (controls), closures with the closure-glass interface covered, and closures
      completely covered with a polyurethane impermeable varnish. The oxygen ingress
      into the bottles was measured by a nondestructive colorimetric method. Technical
      cork stoppers were essentially impermeable to atmospheric oxygen during the first
      24 months of storage. Oxygen within natural corks diffused slowly but
      continuously into the bottles over the first 12 months of storage and in very
      tiny amounts through the cork-glass interface the 12 months thereafter. Nomacorc
      synthetic closures were permeable to atmospheric oxygen, mainly after the first
      month of storage.

PMID- 17542614
TI  - Development of a monoclonal antibody against domoic acid and its application in
      enzyme-linked immunosorbent assay and colloidal gold immunostrip.
AB  - A monoclonal antibody (mAb) specific to domoic acid was produced from a stable
      hybridoma cell line, 9F1F11, generated by the fusion of P3/NS1/1-AG4-1 myeloma
      cells with spleen cells isolated from a Balb/c mouse immunized with domoic acid-
      keyhole limpet hemocyanin. The 9F1F11 mAb belongs to the immunoglobulin G1 (kappa
      chain) isotype. A competitive direct enzyme-linked immunosorbent assay (cdELISA)
      and a competitive indirect ELISA were established for antibody characterization.
      In the cdELISA, the concentration causing 50% inhibition (IC50) of binding of
      domoic acid-horseradish peroxidase to the antibody by domoic acid was found to be
      0.58 ng/mL. A sensitive and rapid mAb-based colloidal gold immunostrip was also
      developed. The immunostrip assay, which has a detection limit of 5 ng/mL for
      domoic acid, can be completed in 10 min. Analysis of domoic acid in blue mussel
      samples revealed that data obtained from immunostrip were in a good agreement
      with those obtained from cdELISA. The mAb-based cdELISA and immunostrip assay
      established in this study were sensitive and accurate for rapid screening of
      domoic acid in shellfish samples.

PMID- 17542615
TI  - effect of dose size on bioavailability of acylated and nonacylated anthocyanins
      from red cabbage (Brassica oleracea L. Var. capitata).
AB  - Recent studies indicate that anthocyanin intake conveys a variety of health
      benefits, which depend on absorption and metabolic mechanisms that deliver
      anthocyanins and their bioactive metabolites to responsive tissues. The
      anthocyanin bioavailability of red cabbage (Brassica oleracea L. var. capitata)
      was evaluated as reflected by urinary excretion of anthocyanins and anthocyanin
      metabolites. Twelve volunteers consumed 100, 200, and 300 g of steamed red
      cabbage (containing 1.38 micromol of anthocyanins/g of cabbage) in a crossover
      design. Anthocyanin concentration in cabbage extract and urine was measured by
      HPLC-MS/MS. Six nonacylated and 30 acylated anthocyanins were detected in red
      cabbage, and 3 nonacylated anthocyanins, 8 acylated anthocyanins, and 4
      metabolites were present in urine. Mean 24 h excretion of intact anthocyanins
      increased linearly from 45 (100 g dose) to 65 nmol (300 g dose) for acylated
      anthocyanins and from 52 (100 g dose) to 79 nmol (300 g dose) for nonacylated
      anthocyanins. Urinary recovery of intact anthocyanins (percent of anthocyanin
      intake) decreased linearly from 0.041% (100 g dose) to 0.020% (300 g dose) for
      acylated anthocyanins and from 0.18% (100 g dose) to 0.09% (300 g dose) for
      nonacylated anthocyanins. Anthocyanin metabolites consisted of glucuronidated and
      methylated anthocyanins. The results show that red cabbage anthocyanins were
      excreted in both intact and metabolized forms and that recovery of nonacylated
      anthocyanins in urine was >4-fold that of acylated anthocyanins.

PMID- 17542616
TI  - Functional analysis of photosystem II in a PsbO-1-deficient mutant in Arabidopsis
      thaliana.
AB  - The Arabidopsis thaliana mutant psbo1 (formerly the mutant LE18-30), which
      contains a point mutation in the psbO-1 gene leading to defective expression of
      the PsbO-1 protein, has recently been described [Murakami, R. et al. (2002) FEBS
      Lett. 523, 138-142]. This mutant completely lacks the PsbO-1 protein and
      overexpresses the PsbO-2 protein. To further study the effect of PsbO-1
      deficiency on the function of photosystem II, the polyphasic chlorophyll a
      fluorescence rise and flash fluorescence induction and decay of the relative
      fluorescence quantum yield were measured in whole leaves from wild type and the
      psbo1 mutant. Additionally, flash oxygen yield experiments were performed on
      thylakoid membranes isolated from wild type and the psbo1 mutant. The results
      obtained indicate that during fluorescence induction the psbo1 gene exhibited an
      enhanced O to P transition. Additionally, while the J to I transition in wild
      type accounted for more than 30% of the total fluorescence yield, in the mutant
      it accounted for less than 2% rise in the total. Analysis of the flash-induced
      fluorescence rise in the presence of DCMU indicated that in wild type the ratio
      of PS IIalpha to PS IIbeta reaction centers was approximately 1.2 while in the
      mutant the ratio was approximately 0.3. Fluorescence decay kinetics in the
      absence of DCMU indicated that electron transfer to QB was significantly altered
      in the mutant. Fluorescence decay kinetics in the presence of DCMU indicated that
      the charge recombination between QA- and the S2 state of the oxygen-evolving
      complex was retarded. Furthermore, flash oxygen yield analysis indicated that
      both the S2 and S3 states exhibited significantly longer lifetimes in the psbo1
      mutant than in wild type. Our data indicate that while PsbO-1-deficient plants
      can grow photoautotrophically (although at a reduced growth rate) the
      photochemistry of PS II is significantly altered.

PMID- 17542617
TI  - Probing the binding site of the A1 adenosine receptor reengineered for orthogonal
      recognition by tailored nucleosides.
AB  - His272 (7.43) in the seventh transmembrane domain (TM7) of the human A3 adenosine
      receptor (AR) interacts with the 3' position of nucleosides, based on selective
      affinity enhancement at a H272E mutant A3 AR (neoceptor) of 3'-ureido, but not 3'
      OH, adenosine analogues. Here, mutation of the analogous H278 of the human A1 AR
      to Ala, Asp, Glu, or Leu enhanced the affinity of novel 2'- and 3'-ureido
      adenosine analogues, such as 10 (N6-cyclopentyl-3'-ureido-3'-deoxyadenosine), by
      >100-fold, while decreasing the affinity or potency of adenosine and other 3'-OH
      adenosine analogues. His278 mutant receptors produced a similar enhancement
      regardless of the charge character of the substituted residue, implicating steric
      rather than electrostatic factors in the gain of function, a hypothesis supported
      by rhodopsin-based molecular modeling. It was also demonstrated that this
      interaction was orientationally specific; i.e., mutations at the neighboring
      Thr277 did not enhance the affinity for a series of 2'- and 3'-ureido
      nucleosides. Additionally, H-bonding groups placed on substituents at the N6 or
      5' position demonstrated no enhancement in the mutant receptors. These
      reengineered human A1 ARs revealed orthogonality similar to that of the A3 but
      not the A2A AR, in which mutation of the corresponding residue, His278, to Asp
      did not enhance nucleoside affinity. Functionally, the H278D A1 AR was detectable
      only in a measure of membrane potential and not in calcium mobilization. This
      neoceptor approach should be useful for the validation of molecular modeling and
      the dissection of promiscuous GPCR signaling.

PMID- 17542618
TI  - Determinants of substrate specificity for saccharopine dehydrogenase from
      Saccharomyces cerevisiae.
AB  - A survey of NADH, alpha-Kg, and lysine analogues has been undertaken in an
      attempt to define the substrate specificity of saccharopine dehydrogenase and to
      identify functional groups on all substrates and dinucleotides important for
      substrate binding. A number of NAD analogues, including NADP, 3-acetylpyridine
      adenine dinucleotide (3-APAD), 3-pyridinealdehyde adenine dinucleotide (3-PAAD),
      and thionicotinamide adenine dinucleotide (thio-NAD), can serve as a substrate in
      the oxidative deamination reaction, as can a number of alpha-keto analogues,
      including glyoxylate, pyruvate, alpha-ketobutyrate, alpha-ketovalerate, alpha
      ketomalonate, and alpha-ketoadipate. Inhibition studies using nucleotide
      analogues suggest that the majority of the binding energy of the dinucleotides
      comes from the AMP portion and that distinctly different conformations are
      generated upon binding of the oxidized and reduced dinucleotides. Addition of the
      2'-phosphate as in NADPH causes poor binding of subsequent substrates but has
      little effect on coenzyme binding and catalysis. In addition, the 10-fold
      decrease in affinity of 3-APAD in comparison to NAD suggests that the
      nicotinamide ring binding pocket is hydrophilic. Extensive inhibition studies
      using aliphatic and aromatic keto acid analogues have been carried out to gain
      insight into the keto acid binding pocket. Data suggest that a side chain with
      three carbons (from the alpha-keto group up to and including the side chain
      carboxylate) is optimal. In addition, the distance between the C1-C2 unit and the
      C5 carboxylate of the alpha-keto acid is also important for binding; the alpha
      oxo group contributes a factor of 10 to affinity. The keto acid binding pocket is
      relatively large and flexible and can accommodate the bulky aromatic ring of a
      pyridine dicarboxylic acid and a negative charge at the C3 but not the C4
      position. However, the amino acid binding site is hydrophobic, and the optimal
      length of the hydrophobic portion of the amino acid carbon side chain is three or
      four carbons. In addition, the amino acid binding pocket can accommodate a branch
      at the gamma-carbon, but not at the beta-carbon.

PMID- 17542619
TI  - Nitration in neurodegeneration: deciphering the "Hows" "nYs".
AB  - Recent literature has ushered in a new awareness of the diverse post
      translational events that can influence protein folding and function. Among these
      modifications, protein nitration is thought to play a critical role in the onset
      and progression of several neurodegenerative diseases. While previously
      considered a late-stage epiphenomenon, nitration of protein tyrosine residues
      appears to be an early event in the lesions of amyotrophic lateral sclerosis,
      Parkinson's disease, and Alzheimer's disease. The advent of highly specific
      biochemical and immunological detection methods reveals that nitration occurs in
      vivo with biological selectively and site specificity. In fact, nitration of only
      a single Tyr residue is often sufficient to induce profound changes in the
      activity of catalytic proteins and the three-dimensional conformation of
      structural proteins. Presumably, nitration modifies protein function by altering
      the hydrophobicity, hydrogen bonding, and electrostatic properties within the
      targeted protein. Most importantly, however, nitrative injury may represent a
      unifying mechanism that explains how genetic and environmental causes of
      neurological disease manifest a singular phenotype. In this review and synthesis,
      we first examine the pathways of protein nitration in biological systems and the
      factors that influence site-directed nitration. Subsequently, we turn our
      attention to the structural implications of site-specific nitration and how it
      affects the function of several neurodegeneration-related proteins. These
      proteins include Mn superoxide dismutase and neurofilament light subunit in
      amyotrophic lateral sclerosis, alpha-synuclein and tyrosine hydroxylase in
      Parkinson's disease, and tau in Alzheimer's disease.

PMID- 17542620
TI  - Insights into the mechanism of flavoprotein-catalyzed amine oxidation from
      nitrogen isotope effects on the reaction of N-methyltryptophan oxidase.
AB  - The mechanism of N-methyltryptophan oxidase, a flavin-dependent amine oxidase
      from Escherichia coli, was studied using a combination of kinetic isotope effects
      and theoretical calculations. The 15(kcat/Km) kinetic isotope effect for
      sarcosine oxidation is pH-dependent with a limiting value of 0.994-0.995 at high
      pH. Density functional theory calculations on model systems were used to
      interpret these isotope effects. The isotope effects are inconsistent with
      proposed mechanisms involving covalent amine-flavin adducts but cannot by
      themselves conclusively distinguish between some discrete electron-transfer
      mechanisms and a direct hydride-transfer mechanism, although the latter mechanism
      is more consistent with the energetics of the reaction.

PMID- 17542621
TI  - Kinetics and mechanism of oxygen-independent hydrocarbon hydroxylation by
      ethylbenzene dehydrogenase.
AB  - Ethylbenzene dehydrogenase (EBDH) from the denitrifying bacterium Azoarcus sp.
      strain EbN1 (to be renamed Aromatoleum aromaticum) catalyzes the oxygen
      independent, stereospecific hydroxylation of ethylbenzene to (S)-1-phenylethanol,
      the first known example of direct anaerobic oxidation of a nonactivated
      hydrocarbon. The enzyme is a trimeric molybdenum/iron-sulfur/heme protein of 155
      kDa that is quickly inactivated in air in its reduced state. Enzyme activity can
      be coupled to ferricenium tetrafluoroborate, providing a convenient way for
      kinetic measurements. EBDH exhibits activity with a wide range of ethylbenzene
      analogues, which were analyzed for their kinetic parameters, stoichiometry, and
      formed products. The reactivity was correlated to the chemical structures by a
      quantitative structure-activity relationship (QSAR) model. On the basis of these
      results, quantum chemical calculations of DeltaG298 for formation of carbocations
      of the respective substrates were performed and used in reactivity analysis. A
      putative reaction mechanism is proposed on the basis of the experimental results
      and theoretical considerations. Finally, the enzyme reaction has been established
      in an electrochemical reactor, allowing sustained enzymatic reaction and
      potential technical applications of the enzyme.

PMID- 17542622
TI  - On the role of aromatic side chains in the photoactivation of BLUF domains.
AB  - BLUF (blue-light sensing using FAD) domain proteins are a novel group of blue
      light sensing receptors found in many microorganisms. The role of the aromatic
      side chains Y21 and W104, which are in close vicinity to the FAD cofactor in the
      AppA BLUF domain from Rhodobacter sphaeroides, is investigated through the
      introduction of several amino acid substitutions at these positions. NMR
      spectroscopy indicated that in the W104F mutant, the local structure of the FAD
      binding pocket was not significantly perturbed as compared to that of the wild
      type. Time-resolved fluorescence and absorption spectroscopy was applied to
      explore the role of Y21 and W104 in AppA BLUF photochemistry. In the Y21 mutants,
      FADH*-W* radical pairs are transiently formed on a ps time scale and recombine to
      the ground state on a ns time scale. The W104F mutant shows a spectral evolution
      similar to that of wild type AppA but with an increased yield of signaling state
      formation. In the Y21F/W104F double mutant, all light-driven electron-transfer
      processes are abolished, and the FAD singlet excited-state evolves by intersystem
      crossing to the triplet state. Our results indicate that two competing light
      driven electron-transfer pathways are available in BLUF domains: one productive
      pathway that involves electron transfer from the tyrosine, which leads to
      signaling state formation, and one nonproductive electron-transfer pathway from
      the tryptophan, which leads to deactivation and the effective lowering of the
      quantum yield of the signaling state formation. Our results are consistent with a
      photoactivation mechanism for BLUF domains where signaling state formation
      proceeds via light-driven electron and proton transfer from the conserved
      tyrosine to FAD, followed by a hydrogen-bond rearrangement and radical-pair
      recombination.

PMID- 17542623
TI  - Activity study of self-assembled proteins on nanoscale diblock copolymer
      templates.
AB  - Novel methods for affixing functional proteins on surfaces with high areal
      density have the potential to promote basic biological research as well as
      various bioarray applications. The use of polymeric templates under carefully
      balanced thermodynamic conditions enables spontaneous, self-assembled protein
      immobilization on surfaces with spatial control on the nanometer scale. To assess
      the full potential of such nanometer-scale protein platforms in biosensing
      applications, we report for the first time the biological activity of proteins on
      diblock copolymer platforms. We utilized horseradish peroxidase, mushroom
      tyrosinase, enhanced green fluorescent protein, bovine immunoglobulin G,
      fluorescein isothiocyanate conjugated anti-bovine IgG, and protein G as model
      systems in our protein activity studies. When specific catalytic functions of HRP
      and MT, immobilized on selective domains of microphase-separated PS-b-PMMA, are
      evaluated over a long period of time, these enzymes retain their catalytic
      activity and stability for well over 3 months. By performing confocal
      fluorescence measurements of self-fluorescing proteins and interacting
      protein/protein systems, we have also demonstrated that the binding behavior of
      these proteins is unaffected by surface immobilization onto PS-b-PMMA diblock
      copolymer microdomains. Our polymer platforms provide highly periodic, high
      density, functional, stable surface-bound proteins with spatial control on the
      nanometer scale. Therefore, our diblock copolymer-guided protein assembly method
      can be extremely beneficial for high-throughput proteomic applications.

PMID- 17542624
TI  - Electrical conductance of hydrophobic membranes or what happens below the
      surface.
AB  - Nanoporous alumina membranes rendered hydrophobic by surface modification via
      covalent attachment of hydrocarbon or fluorocarbon chains conduct electricity via
      surface even when the pores are not filled with electrolyte. The resistance is
      many orders of magnitude higher than for electrolyte-filled membranes and does
      not depend on the electrolyte concentration or pH, but it does depend on the type
      of hydrophobic monolayer and its density. The corresponding surface resistance
      varies from greater than 10(18) Omega per square to less than 3 x 10(9) Omega per
      square. When the hydrophobic monolayer contains a small proportion of photoactive
      spiropyran that is insufficient to switch the surface to hydrophilic after
      spiropyran photoisomerization to the merocyanine form, the membrane resistance
      also becomes light-dependent with a reversible increase of surface resistance by
      as much as 15%. Surface conduction is ascribed to hydration and ionization of the
      alumina surface hydroxyls and the ionizable groups of the hydrophobic surface
      modifiers.

PMID- 17542625
TI  - Facile preparative route to alkanethiolate-coated Au38 nanoparticles:
      postsynthesis core size evolution.
AB  - A facile preparative route to alkanethiolate (Cn) Au38 nanoparticles, where n =
      4, 6, 8, 10, and 12, is described. Subnanometer-sized nanoparticles are initially
      produced by a modified Brust synthesis, which undergo core-size evolution upon
      removal of reaction impurities that have served as additional protecting layers.
      C4-C12 Au38 nanoparticles are prepared in approximately 300 mg quantities by the
      selective removal of reaction impurities with dimethyl sulfoxide. The prepared
      nanoparticles are 1.1-1.2 nm in core size, and all exhibit optical and
      electrochemical characteristics of Au38 nanoparticles. Voltammetry of these Au38
      nanoparticles reveals that the energy gap between the first one-electron
      oxidation and the first reduction is rather insensitive to the ligand employed.
      By contrast, the energy gaps between the first and second oxidations and between
      the second and third oxidations are ligand-dependent; both substantially increase
      with ligand thickness. The charging energetics of alkanethiolate-coated Au38
      nanoparticles can thus be described as a sum of electron addition energies and
      the discrete electronic energy levels of the Au38 core.

PMID- 17542626
TI  - Layer-by-layer growth of oriented metal organic polymers on a functionalized
      organic surface.
AB  - A metal-organic coordination polymer based on benzenetricarboxylic acid ligands
      and Zn(II) ions was grown on a COOH-terminated organic surface in a stepwise
      fashion. The deposited films were characterized using a number of surface
      analysis techniques, including X-ray absorption spectroscopy and X-ray
      photoelectron spectroscopy. IR measurements show that the metal-organic
      coordination polymer grows in a layer-by-layer fashion and can be reversibly
      loaded with NH3. The deposition is very selective and occurs only on COOH
      terminated regions of an organic surface, as demonstrated by AFM measurements.

PMID- 17542627
TI  - Proteome analysis and tissue microarray for profiling protein markers associated
      with lymph node metastasis in colorectal cancer.
AB  - BACKGROUND: Understanding the proteins associated with lymph node metastasis
      (LNM) in colorectal cancer (CRC) will benefit us in the prediction of CRC
      prognosis and provide us new potential targets in the intervention of CRC. The
      aim of this study is to investigate the LNM-associated proteins and to evaluate
      the clinicopathological characteristics of these target proteins' expression in
      CRC. METHODS: Fresh tumor and paired normal mucosa from five cases for each group
      of non-LNM CRC and LNM CRC were analyzed by two-dimensional electrophoresis
      coupled with MALDI-TOF-MS, followed by Western blotting confirmation. In 40
      paraffin-embedded CRC samples, each for non-LNM CRC and LNM CRC, four
      differentially expressed proteins identified by proteomics analysis were detected
      by tissue microarray with immunohistochemistry staining to access the
      clinicopathological characteristics of these proteins in LNM of CRC. RESULTS:
      Twenty-five proteins were found to be differentially expressed between normal
      mucosa and CRC tissue. Increased expression levels of heat shock protein-27 (HSP
      27), glutathione S-transferase (GST), and Annexin II, but a decreased expression
      level of liver-fatty acid binding protein (L-FABP), existed in LNM CRC as
      compared with non-LNM CRC (p<0.01 or p<0.05, respectively). CONCLUSION: The
      techniques of proteomic analysis combined with tissue microarray provide us a
      dramatic tool for screening of LNM-associated proteins in cancer research. The
      increased expression of HSP-27, GST, and Annexin II, but decreased expression of
      L-FABP, suggests a significantly elevated incidence of LNM in CRC.

PMID- 17542628
TI  - Protein-protein interfaces: properties, preferences, and projections.
AB  - Herein, we study the interfaces of a set of 146 transient protein-protein
      interfaces in order to better understand the principles of their interactions. We
      define and generate the protein interface using tools from computational geometry
      and topology and then apply statistical analysis to its residue composition. In
      addition to counting individual occurrences, we evaluate pairing preferences,
      both across and as neighbors on one side of an interface. Likelihood correction
      emphasizes novel and unexpected pairs, such as the His-Cys pair found in most
      complexes of serine proteases with their diverse inhibitors and the Met-Met
      neighbor pair found in unrelated protein interfaces. We also present a
      visualization of the protein interface that allows for facile identification of
      residue-residue contacts and other biochemical properties.

PMID- 17542629
TI  - Effects of bacterial colonization on the porcine intestinal proteome.
AB  - The gastrointestinal tract harbors a complex community of bacteria, of which many
      may be beneficial. Studies of germ-free animal models have shown that the
      gastrointestinal microbiota not only assists in making nutrients available for
      the host but also contributes to intestinal health and development. We studied
      small intestinal protein expression patterns in gnotobiotic pigs maintained germ
      free, or monoassociated with either Lactobacillus fermentum or non-pathogenic
      Escherichia coli. A common reference design in combination with labeling with
      stable isobaric tags allowed the individual comparison of 12 animals. Our results
      showed that bacterial colonization differentially affected mechanisms such as
      proteolysis, epithelial proliferation, and lipid metabolism, which is in good
      agreement with previous studies of other germ-free animal models. We have also
      found that E. coli has a profound effect on actin remodeling and intestinal
      proliferation, which may be related to stimulated migration and turnover of
      enterocytes. Regulations related to L. fermentum colonization involved individual
      markers for immunoregulatory mechanisms.

PMID- 17542630
TI  - Pressure-induced structural transition in n-pentane: a Raman study.
AB  - Pressure-induced Raman spectroscopy studies on n-pentane have been carried out up
      to 17 GPa at ambient temperature. n-Pentane undergoes a liquid-solid transition
      around 3.0 GPa and a solid-solid transition around 12.3 GPa. The intensity ratio
      of the Raman modes related to all-trans conformation (1130 cm-1 and 2850 cm-1) to
      that of gauche conformation (1090 cm-1 and 2922 cm-1) suggests an increase in the
      gauche population conformers above 12.3 GPa. This is accompanied with broadening
      of Raman modes above 12.3 GPa. The high-pressure phase of n-pentane above 12.3
      GPa is a disordered phase where the carbon chains are kinked. The pressure
      induced order-disorder phase transition is different from the behavior of higher
      hydrocarbon like n-heptane.

PMID- 17542631
TI  - Fidelity of the protein structure reconstruction from inter-residue proximity
      constraints.
AB  - Inter-residue proximity constraints obtained in such experiments as cross
      linking/mass spectrometry are important sources of information for protein
      structure determination. A central question in structure determination using
      these constraints is, What is the minimal number of inter-residue constraints
      needed to determine the fold of a protein? It is also unknown how the different
      structural aspects of constraints differentiate their ability in determining the
      native fold and whether there is a rational strategy for selecting constraints
      that feature higher fidelity in structure determination. To shed light on these
      questions, we study the fidelity of protein fold determination using theoretical
      inter-residue proximity constraints derived from protein native structures and
      the effect of various subsets of such constraints on fold determination. We show
      that approximately 70% randomly selected constraints are sufficient for
      determining the fold of a domain (with an average root-mean-square deviation of
      <or=3.4 A from their native structures). We find that random constraint selection
      often outperforms the rational strategy that predominantly favors the constraints
      representing global structural features. To uncover a strategy for constraint
      selection for the optimal structure determination, we study the role of the
      topological properties of these constraints. Interestingly, we do not observe any
      correlation between various simple topological properties of the selected
      constraints, emphasizing different global and local structural features, and the
      performance of these constraints, suggesting that accurate protein structure
      determination relies on a composite of global and local structural information.

PMID- 17542632
TI  - Polymorphic phase behavior of cardiolipin derivatives studied by coarse-grained
      molecular dynamics.
AB  - Cardiolipin (CL) is a negatively charged four acyl chain lipid, associated with
      energy production in bacterial and mitochondrial membranes. Due to the shape of
      CL, negative curvatures of aggregates are favorable if the charges in the head
      group can be reduced. The phase polymorphism of CL, and of associated derivatives
      with 2, 3, 4, or 5 chains, has been determined previously and offers a model
      system in which micellar, lamellar, and inverse hexagonal phases can be observed.
      We present an extension to a previously established coarse-grained molecular
      dynamics model with the aim of reproducing the different CL phases with two
      adjustable parameters: the number of acyl chains and the effective head group
      charge. With molecular dynamics simulations of large lipid systems, we observed
      transitions between different phases on the nanosecond to microsecond time scale.
      Charge screening by high salt or low pH was successfully modeled by a reduction
      of phosphate charge, which led to the adoption of aggregates with more negative
      curvature. Although specific ion binding at the interface and other atomistic
      details are sacrificed in the coarse-grained model, we found that it captures
      general phase features over a large range of aggregate geometries.

PMID- 17542633
TI  - Nonleaching antimicrobial films prepared from surface-modified microfibrillated
      cellulose.
AB  - We have prepared potentially permanent antimicrobial films based on surface
      modified microfibrillated cellulose (MFC). MFC, obtained by disintegration of
      bleached softwood sulfite pulp in a homogenizer, was grafted with the quaternary
      ammonium compound octadecyldimethyl(3-trimethoxysilylpropyl)ammonium chloride
      (ODDMAC) by a simple adsorption-curing process. Films prepared from the ODDMAC
      modified MFC were characterized by Fourier transform infrared spectroscopy (FT
      IR) and X-ray photoelectron spectroscopy (XPS) and tested for antibacterial
      activity against the Gram-positive bacterium Staphylococcus aureus and the Gram
      negative bacteria Escherichia coli and Pseudomonas aeruginosa. The films showed
      substantial antibacterial capacity even at very low concentrations of
      antimicrobial agent immobilized on the surface. A zone of inhibition test
      demonstrated that no ODDMAC diffused into the surroundings, verifying that the
      films were indeed of the nonleaching type.

PMID- 17542634
TI  - Biologically active natural products from Mongolian medicinal plants Scorzonera
      divaricata and Scorzonera pseudodivaricata.
AB  - Chromatographic separation of a crude extract obtained from the aerial parts of
      the Mongolian medicinal plant Scorzonera divaricata yielded the two new quinic
      acid derivatives feruloylpodospermic acids A and B. Both compounds feature a
      feruloyl group and two dihydrocaffeoyl substituents. For feruloylpodospermic acid
      A, the dihydrocaffeic acid substituents were found esterified at positions 1 and
      5 of the quinic acid moiety, while the feruloyl group was attached at position 3.
      For feruloylpodospermic acid B, the substituents were linked at positions 1, 3,
      and 4. The aerial parts of S. pseudodivaricata that are likewise used in
      Mongolian traditional medicine yielded two further new natural products, for
      which the names scorzoneric acid and scorzonerin are proposed. Scorzoneric acid
      is an unusual phenolic compound featuring a central tetrasubstituted phenyl ring
      to which a glucose unit is bound, which in turn is substituted by an esterified
      acyl side chain. Further substituents of the central phenyl ring system include a
      butan-2-one group, which is linked to a second para-substituted phenyl ring
      system. Scorzonerin is a matricarin-based sesquiterpene lactone that carries an
      esterified dihydrocoumaric acid moiety, which in turn is glycosidically bound to
      glucose. The structures of all new compounds were unambiguously established from
      NMR (1H, 13C, COSY, HMBC) spectroscopic and mass spectrometric data. The new
      quinic acid derivatives feruloylpodospermic acids A and B exhibited strong
      antioxidative activity when analyzed in the DPPH (2,2-diphenyl-1-picrylhydrazyl)
      assay.

PMID- 17542635
TI  - Synthesis and photophysical properties of carbazole-based blue light-emitting
      dendrimers.
AB  - A new class of highly fluorescent and stable carbazole-based dendrimers (1-5)
      that contain the ethynylbenzene and diethynylbenzene cores has been synthesized
      and characterized. They show very high extinction coefficients of absorption
      (A(max) approximately 328-353 nm) and high quantum yields of fluorescence
      (lambda(max) approximately 386-437 nm; Phi(F) approximately 0.72-0.89; tau(F)
      approximately 2.09-3.91 ns) in dichloromethane. The quantum yields of
      fluorescence of 1-5 in the solid state are equally high (lambda(max)
      approximately 385-422 nm; Phi(F) approximately 0.40-0.85). These data indicate
      their potential use as blue-emitting materials in organic light-emitting diodes
      (OLEDs).

PMID- 17542636
TI  - Synthesis and decomposition of an ester derivative of the procarcinogen and
      promutagen, PhIP, 2-amino-1-methyl-6-phenyl-1H-imidazo[4,5-b]pyridine: unusual
      nitrenium ion chemistry.
AB  - The food-derived heterocyclic amine (HCA) carcinogen 2-amino-1-methyl-6-phenyl-1H
      imidazo[4,5-b]pyridine, PhIP, is often generated in the highest concentration of
      the HCAs formed during broiling and frying of meat and fish. Although it is
      considered to be an important contributor to human cancer risk from exposure to
      HCAs, the chemistry of PhIP metabolites that presumably react with DNA to
      initiate carcinogenesis has received only cursory attention. We have synthesized
      the ester derivative N-pivaloxy-2-amino-1-methyl-6-phenyl-1H-imidazo[4,5
      b]pyridine, 1b, and investigated its chemistry in aqueous solution. Although 1b
      was too unstable to isolate, we could characterize it by NMR methods in DMF-d7, a
      solvent in which it is stable at -40 degrees C. It decomposed rapidly in aqueous
      solution, but its conjugate acid, 1bH+, is not reactive. The nitrenium ion, 2,
      was trapped by N(3)(-) to form the unusual tetrazole adduct, 16. In the absence
      of N3-, the expected hydration products of 2 were not detected, but the reduction
      product, 12, was detected. Although such products are often taken as evidence of
      triplet nitrenium ions, the efficient trapping of 2 by N(3)(-) indicates that it
      is a ground state singlet species. The product 12 appears to be generated by
      reduction of an initially formed hydration product of 2. An alternative addition
      elimination mechanism for the formation of 12 does not fit the available kinetic
      data. The selectivity of 2, measured as kaz/ks, the ratio of the second-order
      rate constant for its reaction with N(3)(-) and the first-order rate constant for
      its reaction with the aqueous solvent, is (2.3 +/- 0.6) x 10(4) M(-1), a value
      that is in the middle of the range of k(az)/k(s) of 10-10(6) M(-1) observed for
      nitrenium ions derived from other HCAs. The mutagenicity of aromatic amines (AAs)
      and HCAs, measured as the log of histidine revertants per nanomole of amine, log
      m, in Salmonella typhimurium TA 98 and TA 100 correlates with log(k(az)/k(s)) for
      a wide variety of carbocyclic and heterocyclic amine mutagens including PhIP.
      Previously developed linear regression models for mutagenicity that include
      log(k(az)/k(s)) as an independent variable predict log m for PhIP with good
      accuracy in both TA 98 and TA 100. Quantitative carcinogenicity data are less
      strongly correlated with log(k(az)/k(s)), so prediction of the carcinogenicity of
      PhIP and other HCAs or AAs based primarily on log(k(az)/k(s)) is less successful.

PMID- 17542637
TI  - Design and synthesis of chiral N-chloroimidodicarbonates: application to
      asymmetric chlorination of silyl enol ethers.
AB  - New chiral N-chloroimidodicarbonates, which function as efficient chiral
      chlorinating agents, were designed and synthesized. Among these, C(2)-symmetric
      (1R,2S,5R)-(-)-menthyl-N-chloroimidodicarbonate 2a provided moderate to good
      enantioselectivity (up to 40%) for the chlorination of silyl enol ethers to
      afford alpha-chloroketones only in the presence of a suitable Lewis acid such as
      Sm(OTf)(3).

PMID- 17542638
TI  - Magnetic brightening of carbon nanotube photoluminescence through symmetry
      breaking.
AB  - We report that symmetry breaking by a magnetic field can drastically increase the
      photoluminescence quantum yield of single-walled carbon nanotubes, by as much as
      a factor of 6, at low temperatures. To explain this we have developed a
      theoretical model based on field-dependent exciton band structure and the
      interplay of Coulomb interactions and the Aharonov-Bohm effect. This conclusively
      explains our data as the first experimental observation of dark excitons 5-10 meV
      below the bright excitons.

PMID- 17542639
TI  - Group 4 transition metal CH2=MF2, CHF=MF2, and HC/MF3 complexes formed by C-F
      activation and alpha-fluorine transfer.
AB  - Group 4 transition metal methylidene difluoride complexes (CH2=MF2) are formed by
      the reaction of methylene fluoride with laser-ablated metal atoms and are
      isolated in an argon matrix. Isotopic substitution of the CH2F2 precursor and
      theoretical computations (B3LYP and CCSD) confirm product identifications and
      assignments. Our calculations indicate that the CH2=MF2 complexes have near C2v
      symmetry and are considerably more stable than other possible products (CH2(mu
      F)MF and CHF=MHF). The primary reaction exothermicity provides more than enough
      energy to activate the initial bridge-bonded CH2(mu-F)MF products on the triplet
      potential energy surface to complete an alpha-F transfer to form the very stable
      CH2=MF2 products. Analogous experiments with CHF3 produce CHF=TiF2, which is not
      distorted at the C-H bond, whereas the heavier group 4 metals form lower-energy
      triplet HC/MF3 complexes, which contain weak degenerate C(p)-M(d) pi-bonding
      interactions. Comparisons are made with the CH2=MHF methylidene species, which
      showed considerable agostic distortions.

PMID- 17542641
TI  - Hierarchical processing of auditory objects in humans.
AB  - This work examines the computational architecture used by the brain during the
      analysis of the spectral envelope of sounds, an important acoustic feature for
      defining auditory objects. Dynamic causal modelling and Bayesian model selection
      were used to evaluate a family of 16 network models explaining functional
      magnetic resonance imaging responses in the right temporal lobe during spectral
      envelope analysis. The models encode different hypotheses about the effective
      connectivity between Heschl's Gyrus (HG), containing the primary auditory cortex,
      planum temporale (PT), and superior temporal sulcus (STS), and the modulation of
      that coupling during spectral envelope analysis. In particular, we aimed to
      determine whether information processing during spectral envelope analysis takes
      place in a serial or parallel fashion. The analysis provides strong support for a
      serial architecture with connections from HG to PT and from PT to STS and an
      increase of the HG to PT connection during spectral envelope analysis. The work
      supports a computational model of auditory object processing, based on the
      abstraction of spectro-temporal "templates" in the PT before further analysis of
      the abstracted form in anterior temporal lobe areas.

PMID- 17542642
TI  - Cell surface receptors for signal transduction and ligand transport: a design
      principles study.
AB  - Receptors constitute the interface of cells to their external environment. These
      molecules bind specific ligands involved in multiple processes, such as signal
      transduction and nutrient transport. Although a variety of cell surface receptors
      undergo endocytosis, the systems-level design principles that govern the
      evolution of receptor trafficking dynamics are far from fully understood. We have
      constructed a generalized mathematical model of receptor-ligand binding and
      internalization to understand how receptor internalization dynamics encodes
      receptor function and regulation. A given signaling or transport receptor system
      represents a particular implementation of this module with a specific set of
      kinetic parameters. Parametric analysis of the response of receptor systems to
      ligand inputs reveals that receptor systems can be characterized as being: i)
      avidity-controlled where the response control depends primarily on the
      extracellular ligand capture efficiency, ii) consumption-controlled where the
      ability to internalize surface-bound ligand is the primary control parameter, and
      iii) dual-sensitivity where both the avidity and consumption parameters are
      important. We show that the transferrin and low-density lipoprotein receptors are
      avidity-controlled, the vitellogenin receptor is consumption-controlled, and the
      epidermal growth factor receptor is a dual-sensitivity receptor. Significantly,
      we show that ligand-induced endocytosis is a mechanism to enhance the accuracy of
      signaling receptors rather than merely serving to attenuate signaling. Our
      analysis reveals that the location of a receptor system in the avidity
      consumption parameter space can be used to understand both its function and its
      regulation.

PMID- 17542643
TI  - Bottleneck genes and community structure in the cell cycle network of S. pombe.
AB  - The identification of cell cycle-related genes is still a difficult task, even
      for organisms with relatively few genes such as the fission yeast. Several gene
      expression studies have been published on S. pombe showing similarities but also
      discrepancies in their results. We introduce a network in which the weight of
      each link is a function of the phase difference between the expression peaks of
      two genes. The analysis of the stability of the clustering through the
      computation of an entropy parameter reveals a structure made of four clusters,
      the first one corresponding to a robustly connected M-G1 component, the second to
      genes in the S phase, and the third and fourth to two G2 components. They are
      separated by bottleneck structures that appear to correspond to cell cycle
      checkpoints. We identify a number of genes that are located on these bottlenecks.
      They represent a novel group of cell cycle regulatory genes. They all show
      interesting functions, and they are supposed to be involved in the regulation of
      the transition from one phase to the next. We therefore present a comparison of
      the available studies on the fission yeast cell cycle and a general statistical
      bioinformatics methodology to find bottlenecks and gene community structures
      based on recent developments in network theory.

PMID- 17542644
TI  - In search of the biological significance of modular structures in protein
      networks.
AB  - Many complex networks such as computer and social networks exhibit modular
      structures, where links between nodes are much denser within modules than between
      modules. It is widely believed that cellular networks are also modular,
      reflecting the relative independence and coherence of different functional units
      in a cell. While many authors have claimed that observations from the yeast
      protein-protein interaction (PPI) network support the above hypothesis, the
      observed structural modularity may be an artifact because the current PPI data
      include interactions inferred from protein complexes through approaches that
      create modules (e.g., assigning pairwise interactions among all proteins in a
      complex). Here we analyze the yeast PPI network including protein complexes (PIC
      network) and excluding complexes (PEC network). We find that both PIC and PEC
      networks show a significantly greater structural modularity than that of randomly
      rewired networks. Nonetheless, there is little evidence that the structural
      modules correspond to functional units, particularly in the PEC network. More
      disturbingly, there is no evolutionary conservation among yeast, fly, and
      nematode modules at either the whole-module or protein-pair level. Neither is
      there a correlation between the evolutionary or phylogenetic conservation of a
      protein and the extent of its participation in various modules. Using computer
      simulation, we demonstrate that a higher-than-expected modularity can arise
      during network growth through a simple model of gene duplication, without natural
      selection for modularity. Taken together, our results suggest the intriguing
      possibility that the structural modules in the PPI network originated as an
      evolutionary byproduct without biological significance.

PMID- 17542645
TI  - Primary involvement of pharynx and peyer's patch in inhalational and intestinal
      anthrax.
AB  - Bacillus anthracis causes three forms of anthrax: inhalational, gastrointestinal,
      and cutaneous. Anthrax is characterized by both toxemia, which is caused by
      secretion of immunomodulating toxins (lethal toxin and edema toxin), and
      septicemia, which is associated with bacterial encapsulation. Here we report
      that, contrary to the current view of B. anthracis pathogenesis, B. anthracis
      spores germinate and establish infections at the initial site of inoculation in
      both inhalational and cutaneous infections without needing to be transported to
      draining lymph nodes, and that inhaled spores establish initial infection in
      nasal-associated lymphoid tissues. Furthermore, we found that Peyer's patches in
      the mouse intestine are the primary site of bacterial growth after intragastric
      inoculation, thus establishing an animal model of gastrointestinal anthrax. All
      routes of infection progressed to the draining lymph nodes, spleen, lungs, and
      ultimately the blood. These discoveries were made possible through the
      development of a novel dynamic mouse model of B. anthracis infection using
      bioluminescent non-toxinogenic capsulated bacteria that can be visualized within
      the mouse in real-time, and demonstrate the value of in vivo imaging in the
      analysis of B. anthracis infection. Our data imply that previously unrecognized
      portals of bacterial entry demand more intensive investigation, and will
      significantly transform the current perception of inhalational, gastrointestinal,
      and cutaneous B. anthracis pathogenesis.

PMID- 17542646
TI  - Escape of HIV-1 from a small molecule CCR5 inhibitor is not associated with a
      fitness loss.
AB  - Fitness is a parameter used to quantify how well an organism adapts to its
      environment; in the present study, fitness is a measure of how well strains of
      human immunodeficiency virus type 1 (HIV-1) replicate in tissue culture. When HIV
      1 develops resistance in vitro or in vivo to antiretroviral drugs such as reverse
      transcriptase or protease inhibitors, its fitness is often impaired. Here, we
      have investigated whether the development of resistance in vitro to a small
      molecule CCR5 inhibitor, AD101, has an associated fitness cost. To do this, we
      developed a growth-competition assay involving dual infections with molecularly
      cloned viruses that are essentially isogenic outside the env genes under study.
      Real-time TaqMan quantitative PCR (QPCR) was used to quantify each competing
      virus individually via probes specific to different, phenotypically silent target
      sequences engineered within their vif genes. Head-to-head competition assays of
      env clones derived from the AD101 escape mutant isolate, the inhibitor-sensitive
      parental virus, and a passage control virus showed that AD101 resistance was not
      associated with a fitness loss. This observation is consistent with the retention
      of the resistant phenotype when the escape mutant was cultured for a total of 20
      passages in the absence of the selecting compound. Amino acid substitutions in
      the V3 region of gp120 that confer complete AD101 resistance cause a fitness loss
      when introduced into an AD101-sensitive, parental clone; however, in the
      resistant isolate, changes elsewhere in env that occurred prior to the
      substitutions within V3 appear to compensate for the adverse effect of the V3
      changes on replicative capacity. These in vitro studies may have implications for
      the development and management of resistance to other CCR5 inhibitors that are
      being evaluated clinically for the treatment of HIV-1 infection.

PMID- 17542647
TI  - Arabidopsis TFL2/LHP1 specifically associates with genes marked by trimethylation
      of histone H3 lysine 27.
AB  - TERMINAL FLOWER 2/LIKE HETEROCHROMATIN PROTEIN 1 (TFL2/LHP1) is the only
      Arabidopsis protein with overall sequence similarity to the HETEROCHROMATIN
      PROTEIN 1 (HP1) family of metazoans and S. pombe. TFL2/LHP1 represses
      transcription of numerous genes, including the flowering-time genes FLOWERING
      LOCUS T (FT) and FLOWERING LOCUS C (FLC), as well as the floral organ identity
      genes AGAMOUS (AG) and APETALA 3 (AP3). These genes are also regulated by
      proteins of the Polycomb repressive complex 2 (PRC2), and it has been proposed
      that TFL2/LHP1 represents a potential stabilizing factor of PRC2 activity. Here
      we show by chromatin immunoprecipitation and hybridization to an Arabidopsis
      Chromosome 4 tiling array (ChIP-chip) that TFL2/LHP1 associates with hundreds of
      small domains, almost all of which correspond to genes located within
      euchromatin. We investigated the chromatin marks to which TFL2/LHP1 binds and
      show that, in vitro, TFL2/LHP1 binds to histone H3 di- or tri-methylated at
      lysine 9 (H3K9me2 or H3K9me3), the marks recognized by HP1, and to histone H3
      trimethylated at lysine 27 (H3K27me3), the mark deposited by PRC2. However, in
      vivo TFL2/LHP1 association with chromatin occurs almost exclusively and co
      extensively with domains marked by H3K27me3, but not H3K9me2 or -3. Moreover, the
      distribution of H3K27me3 is unaffected in lhp1 mutant plants, indicating that
      unlike PRC2 components, TFL2/LHP1 is not involved in the deposition of this mark.
      Rather, our data suggest that TFL2/LHP1 recognizes specifically H3K27me3 in vivo
      as part of a mechanism that represses the expression of many genes targeted by
      PRC2.

PMID- 17542648
TI  - Whole-genome cartography of estrogen receptor alpha binding sites.
AB  - Using a chromatin immunoprecipitation-paired end diTag cloning and sequencing
      strategy, we mapped estrogen receptor alpha (ERalpha) binding sites in MCF-7
      breast cancer cells. We identified 1,234 high confidence binding clusters of
      which 94% are projected to be bona fide ERalpha binding regions. Only 5% of the
      mapped estrogen receptor binding sites are located within 5 kb upstream of the
      transcriptional start sites of adjacent genes, regions containing the proximal
      promoters, whereas vast majority of the sites are mapped to intronic or distal
      locations (>5 kb from 5' and 3' ends of adjacent transcript), suggesting
      transcriptional regulatory mechanisms over significant physical distances. Of all
      the identified sites, 71% harbored putative full estrogen response elements
      (EREs), 25% bore ERE half sites, and only 4% had no recognizable ERE sequences.
      Genes in the vicinity of ERalpha binding sites were enriched for regulation by
      estradiol in MCF-7 cells, and their expression profiles in patient samples
      segregate ERalpha-positive from ERalpha-negative breast tumors. The expression
      dynamics of the genes adjacent to ERalpha binding sites suggest a direct
      induction of gene expression through binding to ERE-like sequences, whereas
      transcriptional repression by ERalpha appears to be through indirect mechanisms.
      Our analysis also indicates a number of candidate transcription factor binding
      sites adjacent to occupied EREs at frequencies much greater than by chance,
      including the previously reported FOXA1 sites, and demonstrate the potential
      involvement of one such putative adjacent factor, Sp1, in the global regulation
      of ERalpha target genes. Unexpectedly, we found that only 22%-24% of the bona
      fide human ERalpha binding sites were overlapping conserved regions in whole
      genome vertebrate alignments, which suggest limited conservation of functional
      binding sites. Taken together, this genome-scale analysis suggests complex but
      definable rules governing ERalpha binding and gene regulation.

PMID- 17542649
TI  - Mutations in gfpt1 and skiv2l2 cause distinct stage-specific defects in larval
      melanocyte regeneration in zebrafish.
AB  - The establishment of a single cell type regeneration paradigm in the zebrafish
      provides an opportunity to investigate the genetic mechanisms specific to
      regeneration processes. We previously demonstrated that regeneration melanocytes
      arise from cell division of the otherwise quiescent melanocyte precursors
      following larval melanocyte ablation with a small molecule, MoTP. The ease of
      ablating melanocytes by MoTP allows us to conduct a forward genetic screen for
      mechanisms specific to regeneration from such precursors or stem cells. Here, we
      reported the identification of two mutants, eartha(j23e1) and julie(j24e1) from a
      melanocyte ablation screen. Both mutants develop normal larval melanocytes, but
      upon melanocyte ablation, each mutation results in a distinct stage-specific
      defect in melanocyte regeneration. Positional cloning reveals that the
      eartha(j23e1) mutation is a nonsense mutation in gfpt1 (glutamine:fructose-6
      phosphate aminotransferase 1), the rate-limiting enzyme in glucosamine-6
      phosphate biosynthesis. Our analyses reveal that a mutation in gfpt1 specifically
      affects melanocyte differentiation (marked by melanin production) at a late stage
      during regeneration and that gfpt1 acts cell autonomously in melanocytes to
      promote ontogenetic melanocyte darkening. We identified that the julie(j24e1)
      mutation is a splice-site mutation in skiv2l2 (superkiller viralicidic activity 2
      like 2), a predicted DEAD-box RNA helicase. Our in situ analysis reveals that the
      mutation in skiv2l2 causes defects in cell proliferation, suggesting that skiv2l2
      plays a role in regulating melanoblast proliferation during early stages of
      melanocyte regeneration. This finding is consistent with previously described
      role for cell division during larval melanocyte regeneration. The analyses of
      these mutants reveal their stage-specific roles in melanocyte regeneration.
      Interestingly, these mutants identify regeneration-specific functions not only in
      early stages of the regeneration process, but also in late stages of
      differentiation of the regenerating melanocyte. We suggest that mechanisms of
      regeneration identified in this mutant screen may reveal fundamental differences
      between the mechanisms that establish differentiated cells during embryogenesis,
      and those involved in larval or adult growth.

PMID- 17542650
TI  - Genome-wide analysis of KAP1 binding suggests autoregulation of KRAB-ZNFs.
AB  - We performed a genome-scale chromatin immunoprecipitation (ChIP)-chip comparison
      of two modifications (trimethylation of lysine 9 [H3me3K9] and trimethylation of
      lysine 27 [H3me3K27]) of histone H3 in Ntera2 testicular carcinoma cells and in
      three different anatomical sources of primary human fibroblasts. We found that in
      each of the cell types the two modifications were differentially enriched at the
      promoters of the two largest classes of transcription factors. Specifically, zinc
      finger (ZNF) genes were bound by H3me3K9 and homeobox genes were bound by
      H3me3K27. We have previously shown that the Polycomb repressive complex 2 is
      responsible for mediating trimethylation of lysine 27 of histone H3 in human
      cancer cells. In contrast, there is little overlap between H3me3K9 targets and
      components of the Polycomb repressive complex 2, suggesting that a different
      histone methyltransferase is responsible for the H3me3K9 modification. Previous
      studies have shown that SETDB1 can trimethylate H3 on lysine 9, using in vitro or
      artificial tethering assays. SETDB1 is thought to be recruited to chromatin by
      complexes containing the KAP1 corepressor. To determine if a KAP1-containing
      complex mediates trimethylation of the identified H3me3K9 targets, we performed
      ChIP-chip assays and identified KAP1 target genes using human 5-kb promoter
      arrays. We found that a large number of genes of ZNF transcription factors were
      bound by both KAP1 and H3me3K9 in normal and cancer cells. To expand our studies
      of KAP1, we next performed a complete genomic analysis of KAP1 binding using a 38
      array tiling set, identifying ~7,000 KAP1 binding sites. The identified KAP1
      targets were highly enriched for C2H2 ZNFs, especially those containing Kruppel
      associated box (KRAB) domains. Interestingly, although most KAP1 binding sites
      were within core promoter regions, the binding sites near ZNF genes were greatly
      enriched within transcribed regions of the target genes. Because KAP1 is
      recruited to the DNA via interaction with KRAB-ZNF proteins, we suggest that
      expression of KRAB-ZNF genes may be controlled via an auto-regulatory mechanism
      involving KAP1.

PMID- 17542651
TI  - Localizing recent adaptive evolution in the human genome.
AB  - Identifying genomic locations that have experienced selective sweeps is an
      important first step toward understanding the molecular basis of adaptive
      evolution. Using statistical methods that account for the confounding effects of
      population demography, recombination rate variation, and single-nucleotide
      polymorphism ascertainment, while also providing fine-scale estimates of the
      position of the selected site, we analyzed a genomic dataset of 1.2 million human
      single-nucleotide polymorphisms genotyped in African-American, European-American,
      and Chinese samples. We identify 101 regions of the human genome with very strong
      evidence (p < 10(-5)) of a recent selective sweep and where our estimate of the
      position of the selective sweep falls within 100 kb of a known gene. Within these
      regions, genes of biological interest include genes in pigmentation pathways,
      components of the dystrophin protein complex, clusters of olfactory receptors,
      genes involved in nervous system development and function, immune system genes,
      and heat shock genes. We also observe consistent evidence of selective sweeps in
      centromeric regions. In general, we find that recent adaptation is strikingly
      pervasive in the human genome, with as much as 10% of the genome affected by
      linkage to a selective sweep.

PMID- 17542653
TI  - Phonological awareness and rapid naming predict word attack and word
      identification in adults with mild mental retardation.
AB  - In this study we asked whether measures of phonological awareness and rapid
      naming were correlated with single-word reading skills of 30 adults with mild
      mental retardation. We presented four tests of phonological awareness (for rime,
      first, middle, and end-sound categorization), two rapid-naming tests (pictures
      and letters), and the Woodcock Word-Identification and Word-Attack subtests. All
      four phonological-awareness measures and both rapid-naming measures were
      significantly correlated with both word-attack and word-identification skills.
      This outcome is consistent with findings from typically developing children,
      suggesting that instruction in phonological awareness would facilitate the
      acquisition of word-attack skills in individuals with mental retardation.

PMID- 17542652
TI  - Reverse genetic analysis of the yeast RSC chromatin remodeler reveals a role for
      RSC3 and SNF5 homolog 1 in ploidy maintenance.
AB  - The yeast "remodels the structure of chromatin" (RSC) complex is a multi-subunit
      "switching deficient/sucrose non-fermenting" type ATP-dependent nucleosome
      remodeler, with human counterparts that are well-established tumor suppressors.
      Using temperature-inducible degron fusions of all the essential RSC subunits, we
      set out to map RSC requirement as a function of the mitotic cell cycle. We found
      that RSC executes essential functions during G1, G2, and mitosis. Remarkably, we
      observed a doubling of chromosome complements when degron alleles of the RSC
      subunit SFH1, the yeast hSNF5 tumor suppressor ortholog, and RSC3 were combined.
      The requirement for simultaneous deregulation of SFH1 and RSC3 to induce these
      ploidy shifts was eliminated by knockout of the S-phase cyclin CLB5 and by
      transient depletion of replication origin licensing factor Cdc6p. Further,
      combination of the degron alleles of SFH1 and RSC3, with deletion alleles of each
      of the nine Cdc28/Cdk1-associated cyclins, revealed a strong and specific genetic
      interaction between the S-phase cyclin genes CLB5 and RSC3, indicating a role for
      Rsc3p in proper S-phase regulation. Taken together, our results implicate RSC in
      regulation of the G1/S-phase transition and establish a hitherto unanticipated
      role for RSC-mediated chromatin remodeling in ploidy maintenance.

PMID- 17542654
TI  - Effects of microswitch-based programs on indices of happiness of students with
      multiple disabilities: a new research evaluation.
AB  - The effects of microswitch-based programs on indices of happiness were evaluated
      with 9 students who had profound multiple disabilities. Each student received an
      ABAB sequence in which A represented baseline phases and B, intervention phases.
      During the latter phases, microswitches were used to enable the students to
      control preferred environmental stimulation with simple/feasible responses, such
      as hand-pushing and foot-lifting. Results show that all students increased
      microswitch responding during the intervention phases. Seven of them also had
      significant increases in indices of happiness, whereas the other 2 did not. In an
      attempt to shed some light on the reasons underlying the different outcomes, we
      examined procedural and methodological aspects of the study.

PMID- 17542655
TI  - Receptive vocabulary, expressive vocabulary, and speech production of boys with
      fragile X syndrome in comparison to boys with down syndrome.
AB  - Boys with fragile X syndrome with (n = 49) and without (n = 33) characteristics
      of autism spectrum disorder, boys with Down syndrome (39), and typically
      developing boys (n = 41) were compared on standardized measures of receptive
      vocabulary, expressive vocabulary, and speech administered annually over 4 years.
      Three major findings emerged. Boys with fragile X without autism spectrum
      disorder did not differ from the younger typically developing boys in receptive
      and expressive vocabulary and speech production when compared at similar levels
      of nonverbal cognitive skills. Boys with fragile X without autism spectrum
      disorder and typically developing boys had higher receptive vocabulary and speech
      production than did boys with Down syndrome. There were mixed patterns of results
      for the boys with fragile X and characteristics of autism spectrum disorder.

PMID- 17542656
TI  - Emotional responsivity in young children with Williams syndrome.
AB  - The hypothesis that young children with Williams syndrome show higher rates of
      emotional responsivity relative to other children with developmental disabilities
      was explored. Performance of 23 young children with Williams syndrome and 30 MA
      matched children with developmental disabilities of nonspecific etiologies was
      compared on an adaptation of Repacholi and Gopnik's (1997) "Yummy-Yucky" task.
      Results show that children with Williams syndrome were more likely to mimic
      and/or imitate facial affect and vocalizations than children in the mixed
      comparison group. Yet, this increased emotional responsivity did not
      substantially improve decision-making based on the affective display; children
      with Williams syndrome were more likely to attempt to convince the experimenter
      that the disliked food was likable. Implications of a social profile that
      includes enhanced emotional responsivity paired with impaired perspective taking
      are discussed.

PMID- 17542657
TI  - Antisocial and delinquent behaviors in youths with mild or borderline
      disabilities.
AB  - Six types of antisocial and delinquent behaviors (e.g., property destruction and
      authority avoidance) were assessed in 526 youths (11 to 24 years of age) with
      mild to borderline intellectual disabilities and 1,030 11- to 18-year-olds
      without intellectual disabilities. Overall, 10% to 20% of youths with
      intellectual disabilities exhibited some type of antisocial and delinquent
      behavior, which were quite persistent over a 5-year period. Youths who exhibited
      one type of antisocial and delinquent behavior were likely to also exhibit other
      types of such behaviors. Being male, younger, and having behavioral problems
      particularly predicted these behaviors across a 5-year period. Overall, boys but
      not girls with intellectual disabilities exhibited antisocial and delinquent
      behaviors more often than peers without intellectual disabilities. Clinical
      implications and implications for future research are discussed.

PMID- 17542658
TI  - A structured method of assessing dynamic risk factors among sexual abusers with
      intellectual disabilities.
AB  - The nature and severity of dynamic risk factors among a group of 87 adult male
      sexual abusers with intellectual disabilities were examined as was the
      psychometric properties of a new scale designed to measure these risk factors.
      The Treatment Intervention and Progress Scale for Sexual Abusers with
      Intellectual Disabilities (TIPS-ID) is composed of 25 dynamic risk factors linked
      to sexual reoffense. Data analyses indicate support for the item composition and
      reliability of the scale. Ratings from this scale differentiated participants on
      several clinical variables related to problem severity but not on a measure of
      static risk. These results are discussed in terms of their clinical and research
      implications.

PMID- 17542660
TI  - Accuracy of second trimester fetal head circumference and biparietal diameter for
      predicting the time of spontaneous birth.

PMID- 17542661
TI  - Incidence and correlates of cesarean section in a capital city of a middle-income
      country.
AB  - OBJECTIVE: To determine the prevalence and correlates of cesarean deliveries (CS)
      in Beirut. METHODS: A cross-sectional study conducted on 18,837 consecutive
      infants born at nine hospitals from the National Collaborative Perinatal Neonatal
      Network (NCPNN). Stepwise Logistic Regression was performed to determine CS
      correlates. RESULTS: The rate of CS was 26.4% and correlated with socio
      demographic, obstetrical and provider-related variables. Regression analysis
      identified age, paternal occupation, mode of payment, parity, birth weight,
      gestational age, multiple pregnancies, adequate prenatal care, complications
      during pregnancy, body mass index at delivery, hospital teaching status, day of
      the week and year of delivery to be significant correlates of CS. CONCLUSION:
      This study shows an increased CS rate in a middle-income country, and identifies
      the correlates of women delivering by the abdominal route. These correlates may
      be used for effective reduction policies in the future.

PMID- 17542663
TI  - Maternal mortality in Africa.

PMID- 17542664
TI  - Metabolic changes, hypothalamo-pituitary-adrenal axis and oxidative stress after
      short-term starvation in healthy pregnant women.
AB  - AIM: To compare metabolic effects and oxidative stress in pregnant and non
      pregnant women after 12 h of fasting. METHODS: Twenty-six healthy women with
      uncomplicated singleton pregnancies between the 24(th) and 28(th) gestational
      week were recruited. After an overnight fast, venous blood samples and urine
      samples were tested for metabolic parameters characteristic for starvation,
      cortisol and oxidative stress products. Healthy non-pregnant women matched by
      age, body mass index and length of fasting comprised the control group. RESULTS:
      The metabolic parameters beta-hydroxybutyrate and free fatty acids in blood and
      ketones in urine showed no differences in pregnant and non-pregnant women.
      However, the oxidative stress parameters, 8,12-iso-iPF(2alpha)-VI, isoprostanes
      and malondialdehyde were significantly higher in pregnant subjects, as was
      cortisol. CONCLUSION: Healthy pregnant women are exposed to oxidative stress and
      activation of the hypothalamo-pituitary-adrenal axis, but not to metabolic
      changes resembling starvation during short fasting periods in comparison to non
      pregnant healthy women.

PMID- 17542667
TI  - Presence of BRAF V600E in very early stages of papillary thyroid carcinoma.
AB  - OBJECTIVE: Extremely small (often 0.5-4 mm) incidental thyroid malignancies
      (incidental microcarcinomas, IM) might be discovered at histological examination
      after surgery in patients who were operated on for benign thyroid conditions.
      Morphologically, these malignancies have virtually always features of
      differentiated papillary thyroid carcinoma (PTC). Although IM are in general
      considered of little clinical significance their potential malignant behavior
      cannot be ignored. BRAF(V600E) mutation has emerged as the most prevalent genetic
      alteration in PTC. DESIGN: The incidence of BRAF(V600E) was studied in 85
      microdissected cases of IM detected in two series of 334 and 398 patients
      operated on for benign thyroid disease in 2005 and in 2006, respectively. IM
      ranged in size from 0.5 to 4 mm and all featured cytology consistent with the
      diagnosis of PTC. Microdissected lesions were also evaluated for galectin-3
      expression by immunohistochemistry. MAIN OUTCOME: BRAF(V600E) was identified in
      15 out of 85 (17.6%) IM compared to 45% clinically evident PTCs (n = 91) and
      38.3% preoperatively identified microcarcinomas (n = 47). CONCLUSION: These data
      suggest that it is possible to find BRAF(V600E) in IM despite their extremely
      small (<1 mm) size. This is not a formal demonstration that IM can evolve into
      clinical PTC, but on these bases, patients with BRAF(V600E) IM may need to be
      managed more carefully.

PMID- 17542668
TI  - Lymphocyte and immature dendritic cell infiltrates in differentiated, poorly
      differentiated, and undifferentiated thyroid carcinoma.
AB  - OBJECTIVE: Numerous studies indicate that papillary thyroid carcinomas (PTC) with
      lymphocytic infiltrates are associated with a less extensive disease at diagnosis
      and improved disease-free survival. The infiltration of lymphocytes and immature
      CD1a+ dendritic cells (DC) was characterized in papillary, poorly differentiated
      (PDC), and undifferentiated (UC) carcinomas to evaluate their association with
      immunological infiltrates. DESIGN: A series of 527 consecutive cases of thyroid
      carcinoma treated by total thyroidectomy were investigated by histopathological
      and immunohistochemical methods. The inflammatory infiltrate was quantified and
      typed in intratumoral and peritumoral tissues as well as in the controlateral
      lobe. MAIN OUTCOME: The intratumoral infiltrate was strongly reduced or absent in
      PDC and UC. Intense infiltrates were detected in the PTC tall cell variant. In
      all histotypes, the extent of the intratumoral and peritumoral infiltrates was
      comparable. Immature DC were detected in PTCs and markedly reduced in PDC and UC.
      CD1a+ DCs were detected in a small percentage of PDC and UC. CONCLUSIONS: Though
      a relationship between the extent of lymphocyte/DC infiltrates and the prognosis
      of PTCs could not be demonstrated, tumors with poor prognosis (PDCs, UCs) were
      characterized by markedly reduced lymphocyte/DC infiltrates. The study appears to
      confirm the protective role of DC and infiltrating lymphocytes against thyroid
      tumors.

PMID- 17542669
TI  - Crystal structure of the TSH receptor in complex with a thyroid-stimulating
      autoantibody.
AB  - OBJECTIVE: To analyze interactions between the thyroid-stimulating hormone
      receptor (TSHR) and a thyroid-stimulating human monoclonal autoantibody (M22) at
      the molecular level. DESIGN: A complex of part of the TSHR extracellular domain
      (amino acids 1-260; TSHR260) bound to M22 Fab was prepared and purified. Crystals
      suitable for X-ray diffraction analysis were obtained and the structure solved at
      2.55 A resolution. MAIN OUTCOME: TSHR260 comprises of a curved helical tube and
      M22 Fab clasps its concave surface at 90 degrees to the tube length axis. The
      interface buried in the complex is large (2,500 A(2)) and an extensive network of
      ionic, polar, and hydrophobic bonding is involved in the interaction. There is
      virtually no movement in the atoms of M22 residues on the binding interface
      compared to unbound M22 consistent with "lock and key" binding. Mutation of
      residues showing strong interactions in the structure influenced M22 activity,
      indicating that the binding detail observed in the complex reflects interactions
      of M22 with intact, functionally active TSHR. The receptor-binding arrangements
      of the autoantibody are very similar to those reported for follicle-stimulating
      hormone (FSH) binding to the FSH receptor (amino acids 1-268) and consequently to
      those of TSH itself. CONCLUSIONS: It is remarkable that the thyroid-stimulating
      autoantibody shows almost identical receptor-binding features to TSH although the
      structures and origins of these two ligands are very different. Furthermore, our
      structure of the TSHR and its complex with M22 provide foundations for developing
      new strategies to understand and control both glycoprotein hormone receptor
      activation and the autoimmune response to the TSHR.

PMID- 17542670
TI  - Appetite, adiposity, and thyroid function.

PMID- 17542671
TI  - Thyroid and leptin.
AB  - Leptin, which is produced by adipocytes, is known to be an important regulator of
      food intake and energy storage. Disturbance of thyroid function is associated
      with marked changes in both body weight and energy expenditure, and it has
      therefore been the subject of much research to study the mutual roles of leptin
      and thyroid hormones in this respect. Despite intensive research in this field,
      results are still not very clear. The aim of this review has been to update the
      current state of knowledge of leptin related to thyroid pathophysiology.

PMID- 17542672
TI  - Basic endocrine products of adipose tissue in states of thyroid dysfunction.
AB  - Over the past decade it has been established that adipose tissue is capable of
      secreting a variety of hormones, cytokines, growth factors, and other peptides
      that are capable of changing adipocyte biology as well as different organ
      systems, like the central nervous system, liver, pancreas, and skeletal muscles.
      Also, it is well known that changes of thyroid function are associated with
      marked changes in both body weight and energy expenditure. In recent years an
      extensive research is under way to explore the mutual roles of different
      adipokines and thyroid hormones. The aim of this review is to summarize our
      current knowledge on the role of basic peptides of adipose tissue, such as
      adiponectin, interleukin-6, tumor necrosis factor-alpha, and resistin, in states
      of altered thyroid function.

PMID- 17542673
TI  - Appetite regulation: an overview.
AB  - Obesity is a major public health problem associated with morbidity and mortality
      and continues to increase worldwide. This review focuses on the regions of the
      brain that are important in appetite regulation and the circulating factors
      implicated in the control of food intake. The hypothalamus is critical in the
      regulation of food intake containing neural circuits, which produce a number of
      peptides that influence food intake. The arcuate nucleus of the hypothalamus
      produces both orexigenic peptides (agouti-related protein and neuropeptide Y) and
      anorectic peptides (alpha-melanocyte-stimulating hormone and cocaine- and
      amphetamine-related transcript). The lateral hypothalamus produces the orexigenic
      peptides (melanin-concentrating hormone and orexins). Other hypothalamic factors
      recently implicated in appetite regulation include the endocannabinoids, brain
      derived neurotrophic factor, nesfatin-1, AMP-activated protein kinase, mammalian
      target of rapamycin protein, and protein tyrosine phosphatase. Circulating
      factors that affect food intake mediate their effects by signaling to the
      hypothalamus and/or brainstem. A number of circulating factors are produced by
      peripheral organs, for example, leptin by adipose tissue, insulin and pancreatic
      polypeptide by the pancreas, gut hormones (e.g., ghrelin, obestatin, glucagon
      like peptide-1, oxyntomodulin, peptide YY), and triiodothyronine by the thyroid
      gland. Circulating carbohydrates, lipids, and amino acids also affect appetite
      regulation. Knowledge regarding appetite regulation has vastly expanded in recent
      years providing targets for antiobesity drug design.

PMID- 17542674
TI  - Thyroid cancer in HCV-related chronic hepatitis patients: a case-control study.
AB  - OBJECTIVE: The present study prospectively investigated prevalence and features
      of thyroid cancer in patients with hepatitis C virus-related chronic hepatitis
      (HCV+) in comparison to two samples from the general population with different
      iodine intake. DESIGN: We studied the prevalence of thyroid cancer in 308
      unselected HCV+ patients in comparison to two population-based, gender- and age
      matched control groups: 1) 616 subjects from an iodine deficient area; 2) 616
      subjects from an iodine-sufficient area. Thyroid status was assessed by
      measurement of circulating thyroid hormones and autoantibodies, thyroid
      ultrasonography, and when indicated, fine-needle aspiration cytology. MAIN
      OUTCOME: Circulating thyrotropin, anti-thyroglobulin, and anti-thyroperoxidase
      antibodies levels, and the prevalence of hypothyroidism were significantly higher
      in HCV+ patients (p < 0.001 for all). Six patients with papillary thyroid cancer
      were detected among HCV+ patients, whereas no case was observed in control 1 (p =
      0.001), and only one case was observed in control 2 (p = 0.003). In HCV+ patients
      83% with thyroid cancer had evidence of thyroid autoimmunity vs 31% of the other
      HCV+ patients (p = 0.02). CONCLUSIONS: These data suggest a high prevalence of
      thyroid papillary cancer in HCV+ patients, overall in presence of thyroid
      autoimmunity; careful thyroid monitoring is indicated during the follow-up of
      these patients.

PMID- 17542675
TI  - Lipoprotein alterations, hepatic lipase activity, and insulin sensitivity in
      subclinical hypothyroidism: response to L-T(4) treatment.
AB  - Subclinical hypothyroidism (sH) has been associated with atherosclerotic
      cardiovascular disease even in the absence of hypercholesterolemia. OBJECTIVE:
      Our study was designed to assess the hypothesis that other pro-atherogenic
      parameters, such as qualitative lipoprotein changes and insulin resistance, might
      be present in sH. DESIGN AND METHODS: Twenty-one sH women were compared to 11
      female controls matched for body mass index, menopausal status, and age. Before
      and after 6 months of levothyroxine (L-T(4)) treatment, we determined total
      cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein
      (HDL) cholesterol, triglycerides (TG), apoB levels, hepatic lipase (HL) activity
      in postheparin plasma samples, the chemical composition and copper-induced
      oxidation in isolated LDL and homeostasis model assessment (HOMA), quantitative
      insulin sensitivity check index, and insulinogenic index. MAIN OUTCOME: Lipid
      profiles were similar between the two groups. No differences in LDL oxidability
      or the insulin sensitivity assessment parameters were found. HL activity was
      significantly lower in the sH patients: median (range), 13.1 (2.5-26.7) vs. 18.7
      (7.9-28.1) micromol free fatty acids/mL, p < 0.04. The LDL-cholesterol/LDL-TG
      ratio was decreased in sH: 3.9 (1.8-5.5) vs. 4.7 (3.5-6.8), p < 0.02. HL
      negatively correlated with thyroid-stimulating hormone (TSH) levels (r = - 0.504,
      p < 0.01) and positively with LDL-cholesterol/LDL-TG (r = 0.46, p < 0.02).
      Posttreatment results for all these parameters did not differ significantly
      compared to baseline. CONCLUSIONS: Increased levels of TSH are associated to a
      decrease in HL activity, explaining our findings of an LDL particle rich in TG.
      This qualitative lipoprotein alteration suggests a pro-atherogenic pattern in sH.
      Treatment with L-T(4), however, did not correct the basal lipid derangement.

PMID- 17542676
TI  - Diagnostic value of ultrasonography to distinguish between benign and malignant
      lesions in the management of thyroid nodules.
AB  - OBJECTIVE: We analyzed the sonographic characteristics of thyroid nodules and
      assessed the diagnostic value of ultrasonography in order to distinguish between
      benign and malignant lesions in terms of the management of thyroid nodules.
      DESIGN: We retrospectively analyzed the sonographic features of thyroid nodules
      in 580 patients who had been examined with fine-needle aspiration cytology or who
      underwent surgery for a thyroid nodule. The sonographic features that suggested
      malignancy include microcalcifications, an irregular or microlobulated margin,
      marked hypoechogenicity, and a shape that was taller than it was wide. The
      presence of one or more of these features indicated classification as category 3
      (malignant). The absence of all of these features indicated classification as
      category 2 (benign). Presence of an anechogenic cystic nodule was classified as
      category 1 (benign). MAIN OUTCOME: Of 124 lesions classified as category 3, 60 of
      the lesions were malignant. Of 418 lesions classified as category 1 or 2, 409
      were benign. The sensitivity, specificity, positive predictive value, negative
      predictive value, and diagnostic accuracy based on the sonographic classification
      method were 87.0%, 86.5%, 48.4%, 97.8%, and 86.5%, respectively. CONCLUSIONS: Our
      results identified this sonographic classification as a useful tool in the
      differentiation of malignant nodules from benign nodules. In view of the high
      negative predictive value of sonographic classification, a more aggressive
      approach is recommended only for category 3 nodules.

PMID- 17542677
TI  - Acute suppurative thyroiditis with deep neck infection: a case report.
AB  - Thyroid gland suppuration is a rare condition with nonspecific features. For this
      reason, diagnosis is often delayed, which may lead to a life-threatening
      situation. Causative agents are often gram-positive bacteria, such as
      Staphylococcus aureus and Streptococcus pneumoniae. With appropriate antibiotics
      and drainage of the abscess, the prognosis is usually excellent. Herein, we
      describe a unique case of acute suppurative thyroiditis in an adult male
      presenting with nonspecific sore throat after a fish bone injury to the throat.
      The patient had a history of essential hypertension and gouty arthritis. In the
      emergency room, fever, chills, and neck swelling were noted. Thyroid echo and
      computed tomography of the neck revealed the thyroid abscess with deep neck
      infection. The culture of the abscess showed Streptococcus viridans. He recovered
      gradually after parenteral antibiotics and surgical intervention.

PMID- 17542678
TI  - Thyroid involvement in Rosai-Dorfman disease.
AB  - Rosai-Dorfman disease (RDD) with thyroid involvement is extremely rare; we herein
      present the sixth known case with a review of the previously reported five cases
      and discuss the clinicopathological characteristics of this entity. RDD with
      thyroid involvement has occurred only in females with a mean age of 56.3 years,
      which is significantly different from nodal RDD predominantly seen in young
      males. Besides this, autoimmune thyroiditis is frequently associated in RDD with
      thyroid involvement, which raises a suspicion of a common pathogenesis of both
      entities. RDD with thyroid involvement is commonly misdiagnosed preoperatively as
      thyroid malignancy with lymph node metastasis, which may lead to overtreatment
      and postoperative complication. Clinical presentations might be helpful for a
      preoperative differential diagnosis; while thyroid function, sonography, thyroid
      isotope scan, and fine needle aspiration have been less useful. All six cases
      were treated by surgery and complete remission was seen. However, two patients
      with a preoperative diagnosis of benign disease suffered from hypothyroidism due
      to total thyroidectomy.

PMID- 17542679
TI  - Solitary skin metastasis from papillary thyroid carcinoma.

PMID- 17542680
TI  - Supernumerary extraocular muscle in Graves' orbitopathy.

PMID- 17542681
TI  - Severe chemosis in Graves' ophthalmopathy.

PMID- 17542682
TI  - Iodine supplementation for pregnancy and lactation: United States and Canada:
      recommendations of the American Thyroid Association.

PMID- 17542685
TI  - Vascular calcification in middle age and long-term risk of hip fracture: the
      Framingham Study.
AB  - Osteoporosis and atherosclerosis frequently occur in the same individuals and may
      share similar pathogenic mechanisms. This study examined the relation between
      severity of aortic calcification in middle-age years and subsequent risk of hip
      fracture in women and men in the population-based Framingham Study. INTRODUCTION:
      We assessed vascular calcification in women and men in middle age and risk of hip
      fracture at advanced age. MATERIALS AND METHODS: Participants included 2499
      Framingham cohort members (mean age, 61 yr; range, 47-80 yr). Semiquantitative
      methods were used to determine severity of abdominal aortic calcification on
      baseline radiographs. Information on potential confounding factors was obtained
      from study examinations conducted at, or before, baseline radiography. Hip
      fractures were ascertained by active surveillance and confirmed by medical
      records. RESULTS: Thirty-five-year cumulative incidence of hip fracture was 16%
      in women and 5% in men with prevalent aortic calcification at baseline (score 1+)
      and 14% in women and 4% in men without aortic calcification (score 0). Hazard
      ratios (HRs) and 95% CIs for hip fracture did not increase from the lowest to the
      highest category of aortic calcification. HRs were 1.0, 1.2 (95% CI, 0.9-1.8),
      1.2 (95% CI, 0.7-1.9), 1.1 (95% CI, 0.7-1.7), and 1.4 (95% CI, 0.8-2.3) in women
      (p for trend = 0.44) and 1.0, 1.8 (95% CI, 0.8-3.8), 1.8 (95% CI, 0.7-4.6), 1.5
      (95% CI, 0.6-3.9), and 1.2 (95% CI, 0.2-5.7) in men (p for trend = 0.29) for
      aortic calcification scores 0 (reference), 1-4, 4-5, 6-10, and 11+, respectively.
      However, aortic calcification score was strongly associated with increased risk
      of death (p for trend < 0.0001 in women and men). HRs (95% CIs) for mortality
      from the lowest to highest aortic calcification score were 1.0, 1.6 (1.4-1.9),
      1.7 (1.4-2.1), 1.8 (1.5-2.2), and 2.1 (1.7-2.6) for women, and for men were 1.0,
      1.4 (1.1-1.6), 1.4 (1.2-1.8), 1.6 (1.3-2.0), and 1.9 (1.5-2.5). CONCLUSIONS:
      Vascular calcification in middle-aged adults does not increase long-term hip
      fracture risk.

PMID- 17542686
TI  - Quantifying osteoblast and osteocyte apoptosis: challenges and rewards.
AB  - Since the initial demonstration of the phenomenon in murine and human bone
      sections approximately 10 yr ago, appreciation of the biologic significance of
      osteoblast apoptosis has contributed greatly not only to understanding the
      regulation of osteoblast number during physiologic bone remodeling, but also the
      pathogenesis of metabolic bone diseases and the pharmacology of some of the drugs
      used for their treatment. It is now appreciated that all major regulators of bone
      metabolism including bone morphogenetic proteins (BMPs), Wnts, other growth
      factors and cytokines, integrins, estrogens, androgens, glucocorticoids, PTH and
      PTH-related protein (PTHrP), immobilization, and the oxidative stress associated
      with aging contribute to the regulation of osteoblast and osteocyte life span by
      modulating apoptosis. Moreover, osteocyte apoptosis has emerged as an important
      regulator of remodeling on the bone surface and a critical determinant of bone
      strength, independently of bone mass. The detection of apoptotic osteoblasts in
      bone sections remains challenging because apoptosis represents only a tiny
      fraction of the life span of osteoblasts, not unlike a 6-mo-long terminal illness
      in the life of a 75-yr-old human. Importantly, the phenomenon is 50 times less
      common in human bone biopsies because human osteoblasts live longer and are fewer
      in number. Be that as it may, well-controlled assays of apoptosis can yield
      accurate and reproducible estimates of the prevalence of the event, particularly
      in rodents where there is an abundance of osteoblasts for inspection. In this
      perspective, we focus on the biological significance of the phenomenon for
      understanding basic bone biology and the pathogenesis and treatment of metabolic
      bone diseases and discuss limitations of existing techniques for quantifying
      osteoblast apoptosis in human biopsies and their methodologic pitfalls.

PMID- 17542687
TI  - Developments continue in recall of pet food.

PMID- 17542689
TI  - Purification and partial characterization of canine neutrophil elastase and the
      development of an immunoassay for the measurement of canine neutrophil elastase
      in serum obtained from dogs.
AB  - OBJECTIVE: To purify neutrophil elastase (NE) from dog blood and develop and
      validate an ELISA for the measurement of canine NE (cNE) in canine serum as a
      marker for gastrointestinal tract inflammation. SAMPLE POPULATION: Neutrophils
      from 6 dogs immediately after they were euthanatized and serum from 54 healthy
      dogs. PROCEDURES: cNE was purified from blood by use of dextran sedimentation,
      repeated cycles of freezing-thawing and sonication, cation-exchange
      chromatography, and continuous elution electrophoresis. Antibodies against cNE
      were generated in rabbits, and an ELISA was developed and validated by
      determination of sensitivity, dilutional parallelism, spiking recovery, intra
      assay variability, and interassay variability. A reference range was established
      by assaying serum samples from the 54 healthy dogs and by use of the lower 97.5th
      percentile. RESULTS: cNE was successfully purified from blood, and antibodies
      were successfully generated in rabbits. An ELISA was developed with a sensitivity
      of 1,100 mug/L. The reference range was established as < 2,239 mug/L. Ratios of
      observed-to-expected results for dilutional parallelism for 4 serum samples
      ranged from 85.4% to 123.1%. Accuracy, as determined by spiking recovery, ranged
      from 27.1% to 114.0%. Coefficient of variation for 4 serum samples was 14.2%,
      16.0%, 16.8%, and 13.4%, respectively, for intra-assay variability and 15.4%,
      15.0%, 10.5%, and 14.6%, respectively, for interassay variability. CONCLUSIONS
      AND CLINICAL RELEVANCE: The purification protocol used here resulted in rapid and
      reproducible purification of cNE with a high yield. The novel ELISA yielded
      linear results and was accurate and precise. Additional studies are needed to
      evaluate the clinical usefulness of this assay.

PMID- 17542690
TI  - Cardiorespiratory effects and efficacy of morphine sulfate in winter flounder
      (Pseudopleuronectes americanus).
AB  - OBJECTIVE: To assess the cardiorespiratory effects of morphine sulfate and
      evaluate whether morphine blocks cardiac responses to a noxious stimulus in
      winter flounder. ANIMALS: 42 winter flounder (Pseudopleuronectes americanus) that
      were acclimated at 10 degrees C. PROCEDURES: Each fish was fitted with a Doppler
      flow probe around the ventral aorta; cannulae were placed for injection of drug
      or saline (0.9% NaCl) solution and assessments of respiration. Selected
      cardiorespiratory variables were measured in morphine-injected (40 mg/kg, IP [n =
      18] or 17 mg/kg, IV [2]) or saline solution-injected (1.6 mL [22]) fish at
      various intervals. Heart rate and cardiac output (CO) were also measured in
      flounder that were injected with saline solution (n = 19) or morphine (10) and
      received a noxious or innocuous stimulus (injection of 5% acetic acid or saline
      solution SC into a cheek) 50 minutes later. RESULTS: Morphine administration
      promptly induced marked bradycardia (and a concomitant reduction in CO), followed
      by prolonged (> 48 hours) increases in CO and heart rate. Morphine injection only
      transiently affected respiratory rate. Application of a noxious stimulus to
      control flounder resulted in a significant (10%) but transient (< 5 minutes'
      duration) increase in CO, which was completely blocked by prior administration of
      morphine. CONCLUSIONS AND CLINICAL RELEVANCE: Although morphine blocked the
      response to a noxious stimulus in fish, its cardiovascular effects might preclude
      its use in many research situations. Investigation of the dose dependency of
      these cardiovascular effects and their interspecific variation is required to
      determine the applicability of morphine for use in fish.

PMID- 17542691
TI  - Evaluation of avocado and soybean unsaponifiable extracts for treatment of horses
      with experimentally induced osteoarthritis.
AB  - OBJECTIVE: To evaluate the use of a combination of avocado and soybean
      unsaponifiable (ASU) extracts for the treatment of experimentally induced
      osteoarthritis in horses. ANIMALS: 16 horses. PROCEDURES: Osteoarthritis was
      induced via osteochondral fragmentation in 1 middle carpal joint of each horse;
      the other joint underwent a sham operation. Horses were randomly allocated to
      receive oral treatment with ASU extracts (1:2 [avocado-to-soybean] ratio mixed in
      6 mL of molasses; n = 8) or molasses (6 mL) alone (placebo treatment; 8) once
      daily from days 0 to 70. Lameness, response to joint flexion, synovial effusion,
      gross and histologic joint assessments, and serum and synovial fluid biochemical
      data were compared between treatment groups to identify effects of treatment.
      RESULTS: Osteochondral fragmentation induced significant increases in various
      variables indicative of joint pain and disease. Treatment with ASU extracts did
      not have an effect on signs of pain or lameness; however, there was a significant
      reduction in severity of articular cartilage erosion and synovial hemorrhage
      (assessed grossly) and significant increase in articular cartilage
      glycosaminoglycan synthesis, compared with placebo-treated horses. CONCLUSIONS
      AND CLINICAL RELEVANCE: Although treatment with ASU extracts did not decrease
      clinical signs of pain in horses with experimentally induced osteoarthritis,
      there did appear to be a disease-modifying effect of treatment, compared with
      findings in placebo-treated horses. These objective data support the use of ASU
      extracts as a disease-modifying treatment for management of osteoarthritis in
      horses.

PMID- 17542692
TI  - In vitro comparison of the effects of two forms of hydroxyethyl starch solutions
      on platelet function in dogs.
AB  - OBJECTIVE: To evaluate the effect of 2 hydroxyethyl starch (HES) preparations
      (ie, HES solution with a molecular weight of 600 kd and a degree of substitution
      of 0.7 [HES 600/0.7] and a calcium-containing polyionic HES solution with a
      molecular weight of 670 kd and a degree of substitution of 0.75 [HES 670/0.75])
      on canine platelet function. SAMPLE POPULATION: Blood samples from 10 healthy
      adult dogs. PROCEDURES: Dilution of citrated whole blood was performed with
      saline (0.9% NaCl) solution, HES 600/0.7, and HES 670/0.75 at ratios of 1:9 (ie,
      1 part saline solution or colloid to 9 parts whole blood) and 1:3. Measurements
      of time to platelet plug formation in a capillary tube (ie, closure time) were
      made by use of a bench-top platelet function analyzer with collagen and ADP
      platelet agonists. RESULTS: Mean baseline closure time was 68.0 +/- 15.3 seconds.
      A 1:3 dilution of whole blood with saline solution, HES 600/0.7, and HES 670/0.75
      resulted in mean closure times of 85.8 +/- 15.7 seconds, 100.6 +/- 18.6 seconds,
      and 101.6 +/- 16.2 seconds, respectively. Closure time following 1:3 dilution of
      whole blood with saline solution was significantly different from baseline and
      from 1:9 dilution with saline solution. Closure time following 1:3 dilution of
      whole blood with HES 670/0.75 was significantly different from baseline, 1:3 and
      1:9 dilutions with saline solution, and 1:9 dilutions with HES 600/0.7 or HES
      670/0.75. CONCLUSIONS AND CLINICAL RELEVANCE: Saline solution, HES 600/0.7, and
      HES 670/0.75 affect canine platelet function by prolonging closure times; HES
      solutions prolonged closure time to a greater extent than saline solution.

PMID- 17542693
TI  - Association between frontal-sinus size and syringohydromyelia in small-breed
      dogs.
AB  - OBJECTIVE: To determine whether frontal-sinus size is associated with
      syringohydromyelia. SAMPLE POPULATION: Medical records and magnetic resonance
      images of 62 small-breed dogs. PROCEDURES: Medical records and magnetic resonance
      images were reviewed retrospectively for evaluation of frontal-sinus size and
      syringohydromyelia. A Yates-corrected 2-tailed chi2 test was used to determine
      whether an association existed between absent or miniscule frontal sinuses and
      syringohydromyelia. The strength of the association was evaluated by means of
      prevalence and odds ratios. RESULTS: Absent or miniscule air-filled frontal
      sinuses were detected in 28 of 62 (45%) dogs, and syringohydromyelia was detected
      in 12 of 62 (19%) dogs. Syringohydromyelia was detected in 10 of 28 dogs with
      absent or miniscule frontal sinuses (prevalence, 36%; 95% confidence interval,
      16% to 55%) and in 2 of 34 dogs with larger frontal sinuses (prevalence, 6%;
      confidence interval, 0% to 15%). The probability of detecting syringohydromyelia
      in dogs with absent or miniscule air-filled frontal sinuses was significantly
      greater than the probability of detecting it in dogs with larger frontal sinuses.
      The prevalence ratio was 6.1, and the odds ratio was 8.9. CONCLUSIONS AND
      CLINICAL RELEVANCE: An association between frontal-sinus size and
      syringohydromyelia was identified in small-breed dogs, suggesting that the
      pathogenesis of syringohydromyelia in some instances may involve abnormal
      development of the entire or supratentorial part of the cranium, as opposed to
      being limited to the infratentorial part.

PMID- 17542694
TI  - Effects of the cyclooxygenase inhibitor meloxicam on recovery of ischemia-injured
      equine jejunum.
AB  - OBJECTIVE: To determine the effect of meloxicam and flunixin meglumine on
      recovery of ischemia-injured equine jejunum. ANIMALS: 18 horses. PROCEDURES:
      Horses received butorphanol tartrate; were treated IV with saline (0.9% NaCl)
      solution (SS; 12 mL; n = 6), flunixin meglumine (1.1 mg/kg; 6), or meloxicam (0.6
      mg/kg; 6) 1 hour before ischemia was induced for 2 hours in a portion of jejunum;
      and were allowed to recover for 18 hours. Flunixin and SS treatments were
      repeated after 12 hours; all 3 treatments were administered immediately prior to
      euthanasia. Selected clinical variables, postoperative pain scores, and meloxicam
      pharmacokinetic data were evaluated. After euthanasia, assessment of epithelial
      barrier function, histologic evaluation, and western blot analysis of ischemia
      injured and control jejunal mucosa samples from the 3 groups were performed.
      RESULTS: Meloxicam- or flunixin-treated horses had improved postoperative pain
      scores and clinical variables, compared with SS-treated horses. Recovery of
      transepithelial barrier function in ischemia-injured jejunum was inhibited by
      flunixin but permitted similarly by meloxicam and SS treatments. Eighteen hours
      after cessation of ischemia, numbers of neutrophils in ischemia-injured tissue
      were higher in horses treated with meloxicam or flunixin than SS. Plasma
      meloxicam concentrations were similar to those reported previously, but clearance
      was slower. Changes in expression of proteins associated with inflammatory
      responses to ischemic injury and with different drug treatments occurred,
      suggesting cyclooxygenase-independent effects. CONCLUSIONS AND CLINICAL
      RELEVANCE: Although further assessment is needed, these data have suggested that
      IV administration of meloxicam may be a useful alternative to flunixin meglumine
      for postoperative treatment of horses with colic.

PMID- 17542695
TI  - Role of the MAPK(ERK) pathway in regulation of cytokine expression by
      Mycobacterium avium subsp paratuberculosis-exposed bovine monocytes.
AB  - OBJECTIVE: To evaluate the role of the mitogen-activated protein kinase
      extracellular signal-regulated kinase (MAPK(ERK)) pathway in the interaction
      between Mycobacterium avium subsp paratuberculosis (MAP) organisms and bovine
      monocytes. SAMPLE POPULATION: Monocytes obtained from healthy adult Holstein
      dairy cows that were not infected with MAP organisms. PROCEDURES: Monocytes and
      MAP organisms were incubated together with or without a specific inhibitor of the
      MAPK(ERK) pathway (PD98059), and the capacity of monocytes to express tumor
      necrosis factor alpha (TNF)-alpha and interleukin (IL)-10 and -12, produce nitric
      oxide, acidify phagosomes, kill MAP organisms, and undergo apoptosis was
      evaluated. RESULTS: The MAPK(ERK) pathway was activated within 10 minutes after
      addition of MAP organisms to monocytes. Addition of PD98059 to monocyte-MAP
      mixtures decreased monocyte TNF-alpha and IL-12 mRNA expression but had no effect
      on IL-10 mRNA expression. Treatment with PD98059 failed to induce significant
      alterations in phagosome acidification, organism killing, nitric oxide
      production, or apoptosis of MAP-exposed monocytes. CONCLUSIONS AND CLINICAL
      RELEVANCE: Results indicated that the MAPK(ERK) pathway was activated during the
      interaction of MAP organisms with monocytes, which initiated TNF-alpha and IL-12
      mRNA expression but failed to initiate antimicrobial activity. The MAPK(ERK)
      pathway may be involved in initiating proinflammatory and proimmune responses in
      MAP infection in cattle.

PMID- 17542696
TI  - Development and psychometric testing of an instrument designed to measure chronic
      pain in dogs with osteoarthritis.
AB  - OBJECTIVE: To develop and psychometrically test an owner self-administered
      questionnaire designed to assess severity and impact of chronic pain in dogs with
      osteoarthritis. SAMPLE POPULATION: 70 owners of dogs with osteoarthritis and 50
      owners of clinically normal dogs. PROCEDURES: Standard methods for the stepwise
      development and testing of instruments designed to assess subjective states were
      used. Items were generated through focus groups and an expert panel. Items were
      tested for readability and ambiguity, and poorly performing items were removed.
      The reduced set of items was subjected to factor analysis, reliability testing,
      and validity testing. RESULTS: Severity of pain and interference with function
      were 2 factors identified and named on the basis of the items contained in them.
      Cronbach's alpha was 0.93 and 0.89, respectively, suggesting that the items in
      each factor could be assessed as a group to compute factor scores (ie, severity
      score and interference score). The test-retest analysis revealed kappa values of
      0.75 for the severity score and 0.81 for the interference score. Scores
      correlated moderately well (r = 0.51 and 0.50, respectively) with the overall
      quality-of-life (QOL) question, such that as severity and interference scores
      increased, QOL decreased. Clinically normal dogs had significantly lower severity
      and interference scores than dogs with osteoarthritis. CONCLUSIONS AND CLINICAL
      RELEVANCE: A psychometrically sound instrument was developed. Responsiveness
      testing must be conducted to determine whether the questionnaire will be useful
      in reliably obtaining quantifiable assessments from owners regarding the severity
      and impact of chronic pain and its treatment on dogs with osteoarthritis.

PMID- 17542697
TI  - In vitro fluoroquinolone susceptibility of Pseudomonas aeruginosa isolates from
      dogs with ulcerative keratitis.
AB  - OBJECTIVE: To determine the in vitro fluoroquinolone susceptibility profiles of
      Pseudomonas aeruginosa isolates from dogs with ulcerative keratitis. Animals-27
      dogs with P. aeruginosa-associated ulcerative keratitis. PROCEDURES: P.
      aeruginosa isolates from dogs with ulcerative keratitis were collected during a 3
      year period. Isolates were tested by use of the disk diffusion method for their
      susceptibility to 7 fluoroquinolones that are available as commercial ophthalmic
      preparations. The antimicrobials included second- (ciprofloxacin, ofloxacin,
      norfloxacin, and lomefloxacin), third- (levofloxacin), and fourth-generation
      (gatifloxacin and moxifloxacin) fluoroquinolones. Isolates were designated as
      susceptible, intermediate, or resistant to the various antimicrobials. The
      percentage of susceptible isolates was compared among individual fluoroquinolones
      and among fluoroquinolone generations. RESULTS: None of the dogs had received
      topical or systemic fluoroquinolone treatment prior to referral. Twenty-seven P.
      aeruginosa isolates were collected during the study period. In vitro, bacterial
      resistance to the tested fluoroquinolones was infrequently identified (24/ 27
      isolates were susceptible to all fluoroquinolones evaluated); susceptibility
      percentages ranged from 88.9% to 100% for individual antimicrobials. There were
      no significant differences among isolate susceptibilities to the individual
      antimicrobials or among generations of fluoroquinolones. CONCLUSIONS AND CLINICAL
      RELEVANCE: On the basis of these in vitro data, none of the 7 evaluated
      fluoroquinolones (individually or collectively by generation) appeared to offer a
      clinically important advantage in the treatment of P. aeruginosa-associated
      ulcerative keratitis in dogs. Among the P. aeruginosa isolates collected from
      dogs with ulcerative keratitis in this study, the likelihood of susceptibility to
      the fluoroquinolones evaluated was high.

PMID- 17542698
TI  - Prevalence of feline herpesvirus 1, Chlamydophila felis, and Mycoplasma spp DNA
      in conjunctival cells collected from cats with and without conjunctivitis.
AB  - OBJECTIVE: To use PCR assays to determine the prevalence of feline herpesvirus 1
      (FHV-1), Chlamydophila felis, and Mycoplasma spp DNA in conjunctival cells
      collected from cats with and without conjunctivitis; to compare results of
      conventional and real-time fluorogenic PCR assays for amplification of FHV-1 DNA;
      and to determine whether copy numbers of FHV-1 DNA are correlated with
      conjunctivitis. ANIMALS: 55 cats with active conjunctivitis, 39 healthy cats that
      never had conjunctivitis, and 32 cats with a history of conjunctivitis that had
      been resolved for at least 3 months. PROCEDURES: Samples were obtained by rolling
      cotton-tipped applicators on the ventral conjunctiva of awake cats treated
      topically with proparacaine. The DNA was extracted from the swab specimens and
      assessed in PCR assays to detect DNA of FHV-1 (fluorogenic PCR assay and
      conventional PCR assay), Mycoplasma spp (conventional PCR assay), and C felis
      (conventional PCR assay). RESULTS: Overall prevalence rates of FHV-1, C felis,
      and Mycoplasma spp as assessed by the conventional PCR assays were 6.7%, 3.2%,
      and 9.6%, respectively. Percentage concordance between conventional PCR and
      fluorogenic PCR assays for FHV-1 was 92.5%. There were no significant differences
      among the 3 groups of cats for the mean copy number of FHV-1 divided by the copy
      number of glyceraldehyde-3-phosphate dehydrogenase. CONCLUSIONS AND CLINICAL
      RELEVANCE: Mycoplasma spp were the most prevalent organism detected and was
      associated with conjunctivitis. This study could not confirm that there are
      increased copy numbers of FHV-1 DNA in cats with conjunctivitis, compared with
      the copy numbers for cats without conjunctivitis.

PMID- 17542699
TI  - Effects of stimulation of adenosine A2A receptors on lipopolysaccharide-induced
      production of reactive oxygen species by equine neutrophils.
AB  - OBJECTIVE: To assess the anti-inflammatory effects of an adenosine analogue on
      lipopolysaccharide (LPS)-stimulated equine neutrophils. SAMPLE POPULATION:
      Neutrophils obtained from 10 healthy horses. PROCEDURES: An adenosine analogue
      (5'-N-ethylcarboxamidoadenosine [NECA]) was tested for its ability to inhibit
      production of reactive oxygen species (ROS) in LPS-stimulated equine neutrophils.
      Selective adenosine receptor antagonists were used to identify the receptor
      subtype responsible for effects. To assess the mechanism of action of NECA, cAMP
      concentrations were measured, and effects of dibutyryl cAMP (a stable analogue of
      cAMP) and rolipram (a type 4 phosphodiesterase inhibitor) were investigated.
      RESULTS: NECA elicited concentration-dependent inhibition of ROS production that
      was inhibited by ZM241385, a selective adenosine A(2A) receptor antagonist; this
      effect of NECA was not affected by the adenosine A(2B) receptor antagonist
      MRS1706. Also, ZM241385 blocked NECA-induced increases in cAMP concentrations,
      whereas MRS1706 did not alter this effect of NECA. Rolipram potentiated NECA
      induced inhibition of ROS production, and dibutyryl cAMP also inhibited ROS
      production. CONCLUSIONS AND CLINICAL RELEVANCE: Activation of adenosine A(2A)
      receptors inhibited ROS production by LPS-stimulated equine neutrophils in a cAMP
      dependent manner. These results suggest that stable adenosine A(2A) receptor
      agonists may be developed as suitable anti-inflammatory drugs in horses.

PMID- 17542700
TI  - Response of healthy dogs to infusions of human serum albumin.
AB  - OBJECTIVE: To evaluate the clinical and immunologic response in healthy dogs to
      infusions of human serum albumin (HSA). ANIMALS: 9 healthy purpose-bred mixed
      breed dogs. PROCEDURES: Each dog was administered a 25% HSA solution once or
      twice. Various physical examination and laboratory variables were serially
      evaluated. Antibody against HSA was assayed before and after infusion by use of
      an ELISA. Intradermal testing was also conducted. A repeated-measures ANOVA or
      Friedman repeated-measures ANOVA on ranks was used to compare results for the
      variables. RESULTS: Adverse clinical reactions were observed after the first or
      second infusion in 3 dogs. Anaphylactoid reactions were observed in 1 of 9 dogs
      during the first infusion and in 2 of 2 dogs administered a second infusion. Two
      dogs developed severe edema and urticaria 6 or 7 days after an initial infusion.
      All dogs developed anti-HSA antibodies. Positive responses for ID tests were
      observed in 8 of 9 dogs. Short-term increases were detected in blood protein,
      total bilirubin, and calcium concentrations after HSA infusion. Serum cholesterol
      concentrations and platelet counts decreased after HSA infusion. CONCLUSIONS AND
      CLINICAL RELEVANCE: Administration of HSA resulted in profound reactions in 2 of
      9 dogs administered a single infusion and in 2 of 2 dogs administered a second
      infusion. This indicates that there is risk of life-threatening adverse reactions
      to HSA infusion in healthy dogs.

PMID- 17542701
TI  - Evaluation of activation of protein kinase C during agonist-induced constriction
      of veins isolated from the laminar dermis of horses.
AB  - OBJECTIVE: To determine the effects of the protein kinase C (PKC) inhibitor, Ro
      31-8220, on agonist-induced constriction of laminar arteries and veins obtained
      from horses. SAMPLE POPULATION: Laminar arteries and veins obtained from 8 adult
      mixed-breed horses. PROCEDURES: Laminar arteries and veins were isolated and
      mounted on small vessel myographs for the measurement of isometric tension.
      Concentration-response curves were then obtained for the vasoconstrictor agonists
      phenylephrine, 5-hydroxytryptamine, prostaglandin F(2), and endothelin-1. All
      responses were measured with or without the addition of Ro-31-8220 (3 microM).
      RESULTS: Laminar veins were more sensitive to vasoconstrictor agonists than
      laminar arteries, and incubation of laminar veins with Ro-31-8220 resulted in
      significantly smaller agonist-induced contractile responses for all agonists
      tested. In contrast, Ro-31-8220 had no effect on agonist-induced contractile
      responses of laminar arteries. CONCLUSIONS AND CLINICAL RELEVANCE: Results of the
      study were consistent with activation of PKC being confined to agonist-induced
      contraction of laminar veins isolated from the laminar dermis of horses.
      Consequently, the possible involvement of PKC in the venoconstriction observed
      during the development of laminitis is worthy of further investigation.

PMID- 17542702
TI  - Association of expiratory airway dysfunction with marked obesity in healthy adult
      dogs.
AB  - OBJECTIVE: To evaluate the effects of obesity on pulmonary function in healthy
      adult dogs. ANIMALS: 36 Retrievers without cardiopulmonary disease. PROCEDURES:
      Dogs were assigned to 1 of 3 groups on the basis of body condition score (1
      through 9): nonobese (score, 4.5 to 5.5), moderately obese (score, 6.0 to 6.5),
      and markedly obese (score, 7.0 to 9.0). Pulmonary function tests performed in
      conscious dogs included spirometry and measurement of inspiratory and expiratory
      airway resistance (R(aw)) and specific R(aw) (sR(aw)) during normal breathing and
      during hyperpnea via head-out whole-body plethysmography. Functional residual
      capacity (FRC; measured by use of helium dilution), diffusion capacity of lungs
      for carbon monoxide (DLCO), and arterial blood gas variables (PaO(2), PaCO(2),
      and alveolar-arterial gradient) were assessed. RESULTS: During normal breathing,
      body condition score did not influence airway function, DLCO, or arterial blood
      gas variables. During hyperpnea, expiratory sR(aw) was significantly greater in
      markedly obese dogs than nonobese dogs and R(aw) was significantly greater in
      markedly obese dogs, compared with nonobese and moderately obese dogs. Although
      not significantly different, markedly obese dogs had a somewhat lower FRC,
      compared with other dogs. CONCLUSIONS AND CLINICAL RELEVANCE: In dogs, obesity
      appeared to cause airflow limitation during the expiratory phase of breathing,
      but this was only evident during hyperpnea. This suggests that flow limitation is
      dynamic and likely occurs in the distal (rather than proximal) portions of the
      airways. Further studies are warranted to localize the flow-limited segment and
      understand whether obesity is linked to exercise intolerance via airway
      dysfunction in dogs.

PMID- 17542703
TI  - Respiratory mechanics in sedated and nonsedated adult llamas.
AB  - OBJECTIVE: To validate the use of noninvasive pulmonary function testing in
      sedated and nonsedated llamas and establish reference range parameters of
      respiratory mechanical function. ANIMALS: 10 healthy adult llamas. PROCEDURES:
      Pulmonary function testing in llamas included the following: measurement of
      functional residual capacity (FRC) via helium dilution, respiratory inductance
      plethysmography (RIP) to assess breathing pattern and flow limitations,
      esophageal-balloon pneumotachography, and a monofrequency forced oscillatory
      technique (FOT; 1 to 7 Hz) before and after IM administration of xylazine (0.2
      mg/kg). RESULTS: The following mean +/- SD measurements of respiratory function
      were obtained in nonsedated llamas: FRC (5.60 +/- 1.24 L), tidal volume (1.03 +/-
      0.3 L), dynamic compliance (0.83 +/- 0.4 L/cm H(2)O), pulmonary resistance (R(L);
      1.42 +/- 0.54 cm H(2)O/L/s), and respiratory system resistance (2.4 +/- 0.9, 2.3
      +/- 0.7, 2.2 +/- 0.6, 2.7 +/- 0.7, and 2.5 +/- 0.5 cm H(2)O/L/s at 1, 2, 3, 5,
      and 7 Hz, respectively) by use of FOT. Measurements of flow limitations via RIP
      were comparable to other species. Sedation with xylazine induced significant
      increases in R(L) and maximum change in transpulmonary pressure. Following
      sedation, a mean 127% increase in R(L) and mean 116% increase in respiratory
      system resistance were observed across 1 to 7 Hz. The magnitude of change in
      respiratory system resistance increased with decreasing impulse frequency,
      suggesting bronchoconstriction. CONCLUSIONS AND CLINICAL RELEVANCE: Noninvasive
      pulmonary function testing is well tolerated in untrained unsedated llamas. These
      techniques have clinical applications in the diagnosis and treatment of
      respiratory tract disease, although testing should not be performed after
      sedation with xylazine.

PMID- 17542709
TI  - Dr. Richard Gallagher awarded 2006 Margaret Hay Edwards Medal.

PMID- 17542711
TI  - The 2005 Milly Haagedoorn Lecture. Five year survival: an end or a beginning?
AB  - Surviving cancer is now becoming more of a possibility and it appears that, while
      this is clearly an advantage, there is emerging a body of literature reporting
      findings of disadvantage or risk for survivors. This paper examines some of the
      literature on the nature of the group of diseases called cancer and its impact.
      Further, some analysis is made of surviving such a serious and potentially life
      limiting illness. The phenomenon of "5-year survival" is considered as a target
      for cancer patients to achieve and marks a transition from patient to well
      person. Studies of those who have been cured of cancer (as indicated by the 5
      year survival) reveal some consistent data on the psychological and social impact
      that this has on them and those close to them. This has implications for
      practitioners who may need to have additional education and training to assist
      survivors, or be aware of the possible risks to enable early referral to other
      professional disciplines. It has implications for cancer education as the
      evidence base for surviving cancer increases. New and different education
      programs may be required for the practitioners of today and those training for
      the future.

PMID- 17542712
TI  - E. Milly L. Haagedoorn Lecture EACE 2006. Developing oncology nurse education and
      training across Europe.
AB  - Education is an important tool in the development of specialist nursing within
      Europe. Awareness of cancer and its treatment and the impact it has on
      individuals and families helps in reducing negative perceptions and fatalistic
      attitudes. Education not only improves care, but can enhance outcomes; research
      studies have identified that appropriate and timely nursing can make a
      difference. There are several drivers for change within cancer nurse education.
      First, the increasing complexity of cancer treatment delivery plus the shift of
      cancer therapy and support into community and ambulatory settings are demanding
      wider skills. Second, the implementation of the Bologna Process across Europe
      aiming to make study programs compatible and comparable to facilitate
      transparency and academic recognition at a European level. As a result of the
      Bologna declaration, educational systems in most European countries are in the
      process of reform. These changes are an opportunity for cancer nursing to
      establish and constitute a starting point for providing a commonality of
      curricula for cancer nurses across Europe.

PMID- 17542713
TI  - Creating tomorrow's leaders in cancer prevention: a novel interdisciplinary
      career development program in cancer genetics research.
AB  - OBJECTIVE: To prepare oncology, genetics and molecular medicine professionals for
      basic, translational and epidemiological cancer genetics research through
      advanced training in a novel specialized cancer genetics career development
      program (CGCDP). METHODS: Established in 2001, the City of Hope CGCDP is the only
      program in the NCI R25T portfolio focused on interdisciplinary training of
      oncologists and geneticists as cancer genetics and cancer prevention research
      program leaders. Program infrastructure, curriculum, recruitment strategies,
      implementation, evaluation and outcome are described. RESULTS: During the initial
      four-year period, twelve highly qualified health care professionals were
      recruited for cancer genetics academic, experiential, and research training. All
      trainees presented abstracts, published peer-reviewed journal articles, and/or
      were awarded cancer genetics research grants. Most are now in academic/research
      venues, following a cancer genetics research career trajectory. CONCLUSION: The
      CGCDP is an NIH-funded program that has successfully trained doctoral and mid
      level professionals in cancer genetics research. Program graduates are addressing
      the burden of cancer by translating cancer genetics investigations into
      individual risk assessment tools and effective cancer screening and prevention
      interventions.

PMID- 17542714
TI  - Differences in cancer prevention knowledge and experience among medical students
      at three institutions over time.
AB  - BACKGROUND: To evaluate the effect of an enhanced cancer prevention curriculum on
      medical students' changes in knowledge, self-perceived competence, and
      educational experience in cancer prevention during the first three years of
      medical school at three different institutions. METHODS: MANOVAs were used to
      compare the differences in mean knowledge scores and self-reported competence in
      counseling and performing screening exams among the institutions at pre-test and
      post-test, respectively. We also calculated a change score for the two
      institutions that used the same ID codes to track students and used a MANCOVA for
      comparison in order to adjust for pretest scores. Pearson chi-square tests were
      used to compare educational experience. RESULTS: The three schools significantly
      (p < .01) differed from each other in mean knowledge scores and self-perceived
      competence at both survey times. For all three institutions, post-test scores
      were significantly higher than pre-test scores (p < .001). The students of the
      three schools also reported significantly (p < .05) different amounts of
      educational experience in most areas. CONCLUSIONS: The varied amount of direct
      instruction in cancer prevention received by the students at the three
      institutions may account for the variation in outcomes. Findings demonstrate the
      effect of the enhanced curriculum.

PMID- 17542715
TI  - Progress in the pipeline: replication of the minority training program in cancer
      control research.
AB  - BACKGROUND: This paper evaluates the replicability of an NCI-funded
      didactic/experiential program to increase the diversity of doctorally-prepared
      cancer disparities investigators. METHODS: The program was developed and operated
      successfully for three years in Northern California when a replication was
      established at UCLA. Feasibility, process, impact, and outcome measures on UCSF
      and UCLA summer-institute participants were compared. RESULTS: Average
      participant rankings of the influence of the program on intention to apply for a
      doctorate were 9.1/10 (UCSF) and 8.6/10 (UCLA). A total of 22.5% of UCSF and 10%
      of UCLA participants have enrolled in, been accepted by, or completed doctoral
      programs. Among these alumni, 68% (21/31) of UCSF and 60% (3/5) of UCLA
      participants plan to conduct their doctoral research in cancer control.
      CONCLUSIONS: This program has been successfully replicated and has met its
      objective to increase the pipeline of ethnically diverse doctoral-level public
      health researchers. Expansion of the program to other regions of the US is
      feasible and indicated.

PMID- 17542716
TI  - Identifying motivations and barriers to patient participation in clinical trials.
AB  - BACKGROUND: This study assessed cancer patients' knowledge and attitudes towards
      clinical trials (CTs). METHODS: A survey was administered to 100/141 cancer
      outpatients. RESULTS: 82% respondents had heard of CTs, but many could only
      provide limited definitions and perceived them as high risk. About half had
      previously been approached to participate in a trial, and 67% had agreed to
      participate. Factors influencing participation in trials, barriers to
      recruitment, and suggestions for increased recruitment in clinical trials were
      identified. CONCLUSIONS: The findings suggest general support of CTs. Education
      programs are needed to raise awareness, reduce fears, and dispel myths about CT
      participation.

PMID- 17542717
TI  - Partners in research: benefits of a summer research program.
AB  - BACKGROUND: The Partners in Research program provides first-hand research
      experiences for medical, pharmacy, and African-American undergraduate students.
      METHODS: During ten weeks, students participate in on-going cancer research,
      weekly educational sessions, two observational clinic sessions, and at least one
      patient support-community outreach clinic. RESULTS: Over the past six years the
      program has enrolled 155 students. Surveys indicate that most students give the
      course high ratings and would recommend the course to their peers. Follow-up
      shows their continued interest in research. CONCLUSIONS: The program will
      encourage students to pursue careers in cancer research and provide a solid base
      of knowledge to future health care professionals.

PMID- 17542718
TI  - Approaches to tobacco control & lung cancer screening among physician assistants.
AB  - BACKGROUND: This study explores physicians' assistants' (PA) knowledge and
      practice regarding tobacco cessation counseling, approaches to lung cancer early
      detection and management of patients at high risk of developing lung cancer.
      METHODS: A cross-sectional survey design was used to examine approaches to
      tobacco use prevention and the early detection of lung cancer among PAs from
      Western New York State. RESULTS: PAs report promoting use of the nicotine patch,
      nicotine spray and bupropion when counseling smokers on cessation. Reported
      management strategies for a patient at high risk of developing lung cancer were
      not supported by current literature. CONCLUSION: These findings suggest the need
      for professional educational programs aimed not only at conveying the continued
      importance of tobacco cessation counseling, but also information on the
      appropriate management options for patients at increased risk of developing lung
      cancer.

PMID- 17542719
TI  - Factors affecting adoption of tobacco education in dental hygiene programs.
AB  - BACKGROUND: Tobacco cessation interventions provided by health care
      professionals, including dental hygienists can significantly increase the rate of
      tobacco cessation, yet providers feel inadequately prepared to deliver such
      interventions. METHODS: 96 dental hygiene faculty completed a survey measuring
      attitudes, subjective norms, and perceived behavioral control to determine their
      influence on teaching and assessing tobacco cessation intervention competencies.
      RESULTS: Prior experience with providing tobacco cessation counseling,
      perceptions of internal confidence and control of barriers were significantly
      related to covering tobacco-related topics. CONCLUSION: Comprehensive, flexible
      tobacco education curriculum guides may help faculty overcome barriers to
      incorporating tobacco education in dental hygiene programs.

PMID- 17542720
TI  - Self-Identification of smoking status in a middle school population: assessing
      smoking behaviors through students' personal perceptions.
AB  - This study investigates correlates of smoking behaviors among 290 students in a
      Mississippi Delta middle school and how these adolescents identify their own
      smoking behaviors. Self-identified "regular smokers" were more socially exposed
      to smoking, and reported more indications of habitual smoking than "non-smokers,"
      "once in a while smokers" and "ex-smokers." These differences could lead to
      intervention studies that, in addition to traditionally categorized regular
      smokers, recruit adolescent smokers who do not identify themselves as regular
      smokers, but who nevertheless exhibit behaviors characteristic of regular
      smokers.

PMID- 17542721
TI  - The informational needs of newly diagnosed cervical cancer patients who will be
      receiving combined chemoradiation treatment.
AB  - BACKGROUND: Cervical cancer patients experience a range of psychosocial sequelae,
      secondary to both disease and treatment (1, 2). Prevalence studies estimate that
      in the first 3 months following a gynecological cancer diagnosis, 47-70% of women
      experience symptoms of sufficient severity to merit a diagnosis of
      moderate/severe depression or anxiety (3, 4). Psycho-educational interventions
      appear to help in this regard (5). Consequently, Princess Margaret Hospital is
      initiating a psycho-educational group for newly diagnosed cervical cancer
      patients who will be receiving combined chemoradiation. PURPOSE: To offer the
      most effective program possible, this study aimed to define patients'
      informational preferences. METHOD: A retrospective needs assessment was
      conducted, involving women (n = 14) who had completed combined chemoradiation for
      a new cervical cancer diagnosis in the past 5 years. Patients were interviewed
      using a new measure based on previous literature (6, 7), which included both open
      ended and Likert-type questions spanning a variety of topics. RESULTS: Analyses
      revealed treatment-related information to be most important to these women, with
      practical, emotional/social and sexual issues rated as somewhat less important.
      Further, the vast majority of patients stated that having the information they
      wanted when they were preparing for treatment would have reduced anxiety or
      stress, enhanced quality of life, and improved treatment and side effect
      management. Thus, the study's results will guide development of the psycho
      educational group, employing an evidence-based approach to ameliorate patient
      care.

PMID- 17542723
TI  - Events leading to the major recall of pet foods.

PMID- 17542724
TI  - Humane teaching methods: evidence versus bias.

PMID- 17542725
TI  - Foie gras: the two faces of Janus.

PMID- 17542726
TI  - What is your diagnosis? Spinal cord compression.

PMID- 17542727
TI  - What is your diagnosis? Hip joint luxation with secondary osteoarthritis and
      pseudoarthrosis.

PMID- 17542728
TI  - Organizational aspects of disaster preparedness and response.

PMID- 17542729
TI  - The impact of products liability law on veterinary medicine.

PMID- 17542730
TI  - Dietary fats and the skin and coat of dogs.

PMID- 17542731
TI  - Enhancing nontechnical skills, knowledge, aptitudes, and attitudes in the
      veterinary profession through the work of the National Commission on Veterinary
      Economic Issues.

PMID- 17542732
TI  - Evaluation of clinical status, renal function, and hematopoietic variables after
      unilateral nephrectomy in canine kidney donors.
AB  - OBJECTIVE: To determine clinical status and renal and hematopoietic function
      after kidney donation and identify risks associated with kidney donation in dogs.
      DESIGN: Prospective study. ANIMALS: 14 dogs that underwent unilateral nephrectomy
      for kidney donation. PROCEDURES: Records were reviewed retrospectively to collect
      data regarding prenephrectomy clinicopathologic variables. Dogs were reexamined
      prospectively at various times after nephrectomy, and pre- and postnephrectomy
      CBC, serum biochemical analyses, urinalysis, and urine protein-to-urine
      creatinine ratio were compared. Six dogs had postnephrectomy renal volume
      determined ultrasonographically, and 4 of those dogs also underwent scintigraphic
      determination of glomerular filtration rate and renal biopsy. RESULTS: All dogs
      were clinically normal at the time of reevaluation. There were no significant
      differences between prenephrectomy and postnephrectomy values for BUN
      concentration or urine specific gravity. Mean postnephrectomy serum creatinine
      concentration was significantly greater than prenephrectomy concentration. Mean
      serum phosphorus concentration was significantly decreased after nephrectomy, and
      mean Hct, corpuscular volume, and corpuscular hemoglobin concentration were
      significantly increased after nephrectomy. Postnephrectomy renal volume was
      greatest in dogs < 12 months old at the time of surgery. Mean postnephrectomy
      glomerular filtration rate was 2.82 +/- 1.12 mL/kg/ min (1.28 +/- 0.51
      mL/lb/min). Renal biopsy specimens obtained during and after nephrectomy were
      histologically normal. CONCLUSIONS AND CLINICAL RELEVANCE: Renal and
      hematopoietic variables were within reference ranges in dogs examined up to 2.5
      years after unilateral nephrectomy. Compensatory renal hypertrophy was greatest
      in dogs < 1 year of age at donation. Donor age, along with histocompatability,
      may be an important factor in selecting dogs for kidney donation.

PMID- 17542733
TI  - Prevalence of serum antibodies against six Leptospira serovars in healthy dogs.
AB  - OBJECTIVE: To determine the prevalence of antibodies against 6 Leptospira
      serovars and determine risk factors associated with positive Leptospira titers in
      healthy client-owned dogs in Michigan. DESIGN: Cross-sectional study. ANIMALS:
      1,241 healthy dogs at least 4 months of age. PROCEDURES: Dogs were examined by
      veterinarians at private practices. Vaccinated and unvaccinated dogs were
      enrolled in the study, which occurred prior to the availability of a 4-serovar
      (Canicola, Grippotyphosa, Icterohaemorrhagiae, and Pomona) Leptospira vaccine.
      Sera were tested by use of the microscopic agglutination test to determine
      antibody titers against Leptospira serovars Bratislava, Canicola, Grippotyphosa,
      Hardjo, Icterohaemorrhagiae, and Pomona. A questionnaire was used to collect
      demographic information about each dog to identify risk factors associated with
      seropositive status. RESULTS: 309 of 1,241 (24.9%) dogs had antibody titers
      against at least 1 of the 6 Leptospira serovars, which suggested exposure to
      Leptospira spp. Prevalence of antibodies was highest to serovar Grippotyphosa,
      followed by Bratislava, Canicola, Icterohaemorrhagiae, and Pomona. Age, travel
      outside Michigan, exercise outside fenced yards, and exposure to livestock and
      wildlife were significant risk factors for positive titers. CONCLUSIONS AND
      CLINICAL RELEVANCE: Among healthy dogs from the lower peninsula of Michigan, >
      20% have antibodies against leptospiral serovars historically considered uncommon
      but more recently incriminated as causing clinical canine leptospirosis. Wildlife
      and livestock may be of increasing importance as reservoirs for canine
      leptospirosis as urbanization continues to occur. Expanded vaccination strategies
      may partially mitigate these trends.

PMID- 17542734
TI  - Intrathecal morphine overdose in a dog.
AB  - CASE DESCRIPTION: A healthy 6-year-old 28.5-kg (62.7-lb) spayed female Boxer
      undergoing surgical repair of a ruptured cranial cruciate ligament was
      inadvertently administered an overdose of morphine (1.3 mg/kg [0.59 mg/lb]) via
      subarachnoid injection. CLINICAL FINDINGS: 50 minutes after administration of the
      overdose, mild multifocal myoclonic contractions became apparent at the level of
      the tail; the contractions migrated cranially and progressively increased in
      intensity and frequency during completion of the surgery. TREATMENT AND OUTCOME:
      The myoclonic contractions were refractory to treatment with midazolam, naloxone,
      phenobarbital, and pentobarbital; only atracurium (0.1 mg/kg [0.045 mg/lb], IV)
      was effective in controlling the movements. The dog developed hypertension,
      dysphoria, hyperthermia, and hypercapnia. The dog remained anesthetized and
      ventilated mechanically; treatments included continuous rate IV infusions of
      propofol (1 mg/kg/h [0.45 mg/lb/h]), diazepam (0.25 mg/kg/h [0.11 mg/lb/h]),
      atracurium (0.1 to 0.3 mg/kg/h [0.045 to 0.14 mg/lb/h]), and naloxone (0.02
      mg/kg/h [0.009 mg/lb/h]). Twenty-two hours after the overdose, the myoclonus was
      no longer present, and the dog was able to ventilate without mechanical
      assistance. The dog remained sedated until 60 hours after the overdose, at which
      time its mentation improved, including recognition of caregivers and response to
      voice commands. No neurologic abnormalities were detectable at discharge (approx
      68 hours after the overdose) or at a recheck evaluation 1 week later. CLINICAL
      RELEVANCE: Although intrathecal administration of an overdose of morphine can be
      associated with major and potentially fatal complications, it is possible that
      affected dogs can completely recover with immediate treatment and extensive
      supportive care.

PMID- 17542735
TI  - Use of vacuum-assisted closure for management of a large skin wound in a cat.
AB  - CASE DESCRIPTION: A 9-month-old domestic shorthair cat was evaluated after being
      struck by a car. CLINICAL FINDINGS: The cat had a fractured tibia and avulsion of
      the tail base. Motor and deep pain sensation were absent from the tail. The
      fractured tibia was repaired 2 days after the trauma. On the third day, the cat
      developed tachypnea, dyspnea, high serum urea nitrogen and total bilirubin
      concentrations, epistaxis, persistent hypotension, and oliguria. The cat
      recovered with supportive care but developed extensive necrosis of the skin on
      the dorsum by 9 days after the initial trauma. TREATMENT AND OUTCOME: The skin
      was debrided from the caudal portion of the scapula to the anus and down each
      pelvic limb to the level of the distal portion of the femur. The tail was
      amputated. Wet-to-dry bandages were applied to the wound for 3 days.
      Approximately 50% of the wound underwent delayed primary closure, and the
      remainder was managed with vacuum-assisted closure. A healthy granulation bed was
      quickly established. Vacuum-assisted closure was also applied after graft
      application. Graft acceptance was 100%, and use of the vacuum-assisted closure
      bandage was not associated with the complications associated with the traditional
      bandage. CLINICAL RELEVANCE: Vacuum-assisted closure is a useful, easily
      applicable technique for open and grafted wounds, even when wounds are in
      challenging anatomic locations.

PMID- 17542736
TI  - Progression of radiographic evidence of osteoarthritis following tibial plateau
      leveling osteotomy in dogs with cranial cruciate ligament rupture: 295 cases
      (2001-2005).
AB  - OBJECTIVE: To determine whether radiographic signs of osteoarthritis became
      progressively worse and tibial slope angle (TSA) changed substantially following
      tibial plateau leveling osteotomy for treatment of cranial cruciate ligament
      rupture in dogs. DESIGN: Retrospective case series. ANIMALS: 295 dogs (373 stifle
      joints). PROCEDURES: Medical records were reviewed. Radiographs obtained before
      and 8 weeks after surgery were used to determine the degenerative joint disease
      (DJD) score, calculated as the sum of individual scores (0 through 3) assigned to
      30 radiographic factors. Radiographs obtained immediately and 8 weeks after
      surgery were used to measureTSA. For dogs that underwent bilateral surgery, data
      for the first joint treated were used in analyses. Data for the second joint
      treated in dogs that underwent bilateral surgery were analyzed separately.
      RESULTS: A small, but significant, increase was found in mean DJD score 8 weeks
      after surgery, compared with mean preoperative score. An inverse relationship was
      found between preoperative DJD score and the difference between postoperative and
      preoperative DJD scores. Mean TSA 8 weeks after surgery was significantly higher
      than mean TSA immediately after surgery. Analysis of data for the second stifle
      joints in the 78 dogs that underwent bilateral surgery yielded similar results.
      CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that there was a small, but
      measurable, increase in the severity of radiographic changes attributed to
      osteoarthritis in the stifle joints of dogs that underwent tibial plateau
      leveling osteotomy because of cranial cruciate ligament rupture.

PMID- 17542738
TI  - Effects of short-term light to heavy exercise on gastric ulcer development in
      horses and efficacy of omeprazole paste in preventing gastric ulceration.
AB  - OBJECTIVE: To determine the effects of 8 days of light to heavy exercise on
      gastric ulcer development in horses and determine the efficacy of omeprazole
      paste in preventing gastric ulceration. DESIGN: Randomized, controlled,
      multicenter clinical trial. ANIMALS: 102 horses with normal-appearing gastric
      mucosa on endoscopic examination that were in light to heavy training.
      PROCEDURES: Horses at 4 trial locations were allocated into replicates and sham
      dosed orally (empty syringe) or treated with a paste formulation of omeprazole (1
      mg/kg [0.45 mg/ lb], PO) once daily for 8 days. Training regimens varied among
      locations and included early training for western performance events; walking,
      trotting, and cantering in a mechanical exerciser; and race training (2
      locations). Prevalences of gastric ulceration at the completion of the 8-day
      treatment period were compared between groups. RESULTS: At the end of the 8-day
      treatment period, the proportion of omeprazole-treated horses free from gastric
      ulceration (88%) was significantly higher than the proportion of sham-dosed
      horses free from gastric ulceration (27%). CONCLUSIONS AND CLINICAL RELEVANCE:
      Results showed that horses in light to heavy training for as short as 8 days were
      at risk of developing gastric ulcers and that administration of omeprazole paste
      decreased the incidence of gastric ulcers.

PMID- 17542739
TI  - Septic osteitis of the distal phalanx in foals: 22 cases (1995-2002).
AB  - OBJECTIVE: To determine the clinical characteristics and outcome of foals with
      septic osteitis of the distal phalanx. DESIGN: Retrospective case series.
      ANIMALS: 22 foals. PROCEDURES: Information obtained from medical records included
      signalment; clinical, laboratory, and radiographic findings; treatment method;
      and outcome. Foals included in the study had lameness referable to the foot,
      radiographic evidence of localized lysis or focal loss of bone density of the
      distal phalanx, and suppurative discharge or necrosis of the affected bone
      evident at surgery. Foals with a history or evidence of penetrating wounds or
      subsolar abscessation were excluded. RESULTS: Mean age of foals at initial
      evaluation was 40.8 days (range, 3 to 122 days). Twenty-one (95%) foals had
      lameness as the primary complaint. Lesions consistent with septic osteitis of the
      distal phalanx localized to specific areas of the bone on the basis of
      radiographic and surgical findings were located on the solar margin or toe (14/22
      [64%]), extensor process (5/22 [23%]), and palmar or plantar process (3/22
      [13%]). Hind limbs (18/26 [69%] affected limbs) were more frequently affected.
      Two foals had > 1 affected limb, 2 had additional sites of osteomyelitis, and 4
      had concurrent septic arthritis. Surgical debridement and regional antimicrobial
      perfusion were performed during general anesthesia. Extensor process lesions were
      not debrided. Nineteen of 22 (86%) foals survived to be discharged from hospital,
      and 16 horses reached racing age. Eleven of 16 had race starts, of which 8 had
      official race starts and 3 had unofficial race starts. CONCLUSIONS AND CLINICAL
      RELEVANCE: Septic osteitis of the distal phalanx should be considered as a source
      of lameness in foals with signs referable to the foot and does not necessarily
      preclude a career in racing. Although infection may occur secondary to bacterial
      penetration of the hoof or sole, the distal phalanx should also be considered as
      a potential site for hematogenous septic arthritis or osteomyelitis in foals.

PMID- 17542740
TI  - Prevalence of calves persistently infected with bovine viral diarrhea virus in
      beef cow-calf herds enrolled in a voluntary screening project.
AB  - OBJECTIVE: To report the prevalence of bovine viral diarrhea virus (BVDV) in
      calves and calf groups (ie, calves from the same farm) in beef breeding herds and
      evaluate the ability of biosecurity risk assessment questionnaires to identify
      calf groups with positive results for BVDV. DESIGN: Nonrandom survey. ANIMALS:
      12,030 calves born in spring from 102 operations. PROCEDURES: Cow-calf producers
      that voluntarily enrolled in a screening project submitted ear notch specimens
      from calves and answered a 29-question survey instrument. Ear notch specimens
      were tested for BVDV with an antigen-capture ELISA (ACE), and ear notch specimens
      with positive ACE results for BVDV were immediately retested by performing
      immunohistochemistry (IHC). Follow-up testing, 3 to 4 weeks after initial
      positive ACE results, was done by use of a second IHC test and virus isolation on
      a subsequently submitted ear notch specimen from the same calves to identify
      those that were persistently infected (PI). RESULTS: 102 producers submitted ear
      notch specimens for BVDV screening. Initially, 24 of 12,030 calves had positive
      ACE results for BVDV. A second ear notch specimen was submitted for 20 of these
      24 calves. Of 20 retested calves, 12 had positive ICH results for BVDV,
      confirming PI status. The 12 PI calves came from 4 calf groups (3 singletons and
      1 calf group with 9 PI calves). CONCLUSIONS AND CLINICAL RELEVANCE: Prevalence of
      BVDV in calf groups was low, and questions designed to identify high-risk
      biosecurity behaviors had little value in identifying calf groups with positive
      results for BVDV.

PMID- 17542741
TI  - Towards the development of a therapeutic vaccine for the treatment of HIV-1
      infection: are we closer than ever?

PMID- 17542742
TI  - Vi polysaccharide-protein conjugate vaccine for the prevention of typhoid fever
      in children: hope or hype?

PMID- 17542743
TI  - Vaccination with the pneumococcal 7-valent conjugate: a successful experiment but
      the species is adapting.

PMID- 17542744
TI  - Artificial antigens for HIV vaccine design.

PMID- 17542745
TI  - Nasal influenza vaccine enters Phase I clinical trial.

PMID- 17542746
TI  - BiovaxID idiotype vaccination: active immunotherapy for follicular lymphoma.
AB  - Although advanced-stage follicular lymphoma (FL) has been considered incurable
      with standard therapy, novel strategies that utilize immunotherapy provide
      opportunities for prolonging disease-free survival. While passive immunotherapy
      with antibodies targeting the CD20 antigen on B cells has been the most widely
      applied lymphoma immunotherapy, active immunization with vaccines derived from
      the immunoglobulin idiotype present on the surface of FL provides an opportunity
      to induce specific humoral and cellular immune responses to the tumor, and have
      been demonstrated to produce significant benefits in prolonging disease-free
      survival. Promoting the benefits of all forms of immunotherapy will likely depend
      upon improving complete remission rates with initial treatment. BiovaxID, a
      patient-specific idiotype vaccine, has demonstrated durable remissions when
      administered to FL patients in first complete remission along with keyhole limpet
      hemocyanin and granulocyte-macrophage colony-stimulating factor, and is now
      undergoing evaluation in a pivotal Phase III clinical trial.

PMID- 17542747
TI  - HIV-1 rational vaccine design: molecular details of b12-gp120 complex structure.

PMID- 17542748
TI  - Oral vaccination against bovine tuberculosis with Mycobacterium bovis BCG.
AB  - The use of a bacillus Calmette-Guerin (BCG)-based vaccine could represent a
      viable strategy for controlling bovine tuberculosis (TB), principally in those
      cases where a wildlife disease vector exists. This article focuses on recent
      progress in animal TB vaccinology, outlining that oral-route vaccination
      represents the most feasible means of distributing a vaccine to control disease
      in wildlife. Drawing on historical successes of previous wildlife vaccination
      programs, the article suggests how, and in what form, an oral-delivery BCG-based
      vaccine might become operational, considering the wide diversity of TB reservoir
      species and the inherent problems associated with field delivery of a live
      attenuated microbial vaccine.

PMID- 17542749
TI  - Optimizing dendritic cell-based immunotherapy for cancer.
AB  - Dendritic cells (DCs) are the most powerful professional antigen-presenting cells
      and are unique in their capability to initiate, maintain and regulate the
      intensity of primary immune responses, including specific antitumor responses.
      Development of practical procedures to prepare sufficient numbers of functional
      human DCs in culture from the peripheral blood precursors, paved the way for
      clinical trials to evaluate various DC-based strategies in patients with
      malignant diseases. However, no definite conclusions regarding the clinical and
      even immunological efficacy of DC vaccination can be stated, despite the fact
      that 12 years have passed since the first clinical trial utilizing DCs in cancer
      patients. Many unanswered questions hamper the development of DC-based vaccines,
      including the source of DC preparation and protocols for DC generation,
      activation and loading with tumor antigens, source of tumor antigens, route of
      vaccine administration and methods of immunomonitoring. Fortunately, in spite of
      the many obstacles, DC vaccines continue to hold promise for cancer therapy.

PMID- 17542750
TI  - T-cell immunity generated by recombinant adenovirus vaccines.
AB  - Recombinant adenovirus vaccines show great promise for generating protective
      immunity against infectious agents and tumors. Our studies have identified
      several interesting biological features of the adenovirus vector that influence
      the T-cell response. Notably, we have demonstrated that following immunization
      with adenovirus vaccines, the transgene antigen remains available to the system
      for a longer period than would be expected, resulting in a T-cell population with
      a sustained effector phenotype. The implications of these observations with
      regards to the utility of adenovirus vaccines are discussed.

PMID- 17542751
TI  - Immunodominance in CD4 T-cell responses: implications for immune responses to
      influenza virus and for vaccine design.
AB  - CD4 T cells play a primary role in regulating immune responses to pathogenic
      organisms and to vaccines. Antigen-specific CD4 T cells provide cognate help to B
      cells, a requisite event for immunoglobulin switch and affinity maturation of B
      cells that produce neutralizing antibodies and also provide help to cytotoxic CD8
      T cells, critical for their expansion and persistence as memory cells. Finally,
      CD4 T cells may participate directly in pathogen clearance via cell-mediated
      cytotoxicity or through production of cytokines. Understanding the role of CD4 T
      cell immunity to viruses and other pathogens, as well as evaluation of the
      efficacy of vaccines, requires insight into the specificity of CD4 T cells. This
      review focuses on the events within antigen-presenting cells that focus CD4 T
      cells toward a limited number of peptide antigens within the pathogen or vaccine.
      The molecular events are discussed in light of the special challenges that the
      influenza virus poses, owing to the high degree of genetic variability,
      unpredictable pathogenicity and the repeated encounters that human populations
      face with this highly infectious pathogenic organism.

PMID- 17542752
TI  - Cell-mediated immune responses induced by BHV-1: rational vaccine design.
AB  - Bovine herpesvirus-1 (BHV-1) is one of the major respiratory pathogens in cattle
      worldwide. Although antibodies have been correlated with protection and recovery
      from BHV-1 infection, the cell-mediated immune response is also a critical
      defense mechanism because cell-to-cell spread occurs before hematogenous spread.
      Furthermore, induction of robust T-cell memory is critical for the long-term
      duration of immunity. Among current commercial vaccines, the attenuated
      conventional vaccines induce a balanced immune response and long-term memory but
      may result in viral shedding. By contrast, inactivated vaccines primarily elicit
      a humoral immune response and relative short-term memory. These vaccines do not
      allow differentiation of vaccinated from infected cattle. Recent efforts are
      focusing on the development of vaccines that induce a balanced immune response
      and long-term memory, as well as having differentiation markers. This includes
      well-defined genetically engineered gene-deleted, subunit and vectored vaccines.

PMID- 17542753
TI  - Virus-like particles: flexible platforms for vaccine development.
AB  - Virus-like particles (VLPs) consist of viral structural proteins that, when
      overexpressed, spontaneously self-assemble into particles that are antigenically
      indistinguishable from infectious virus or subviral particles. VLPs can be
      considered as dense, repetitive arrays of one or more protein subunits with
      properties that are highly advantageous for use as stand-alone vaccines or as
      vaccine platforms. This review discusses the development of VLP-based platform
      technologies for vaccines against pathogens, as well as nontraditional targets
      such as self-antigens involved in chronic diseases.

PMID- 17542754
TI  - Smart adjuvants.
AB  - Although vaccine adjuvants have been used for almost a century, alum is the only
      adjuvant licensed by the US FDA for human vaccine use. Many adjuvants studied to
      date have generalized inflammatory properties and lack specificity in terms of
      targeting immune compartments and cell populations. Indeed, such adjuvants have
      often been crude in formulation, their effects usually restricted to T-helper 2
      type immunity and their use limited owing to inherent toxicity. However, recent
      advances in immunology have resulted in a number of potential adjuvant candidates
      that are able to modulate the immune response in a more controlled and specific
      manner. These novel adjuvants are attractive for inclusion in current and future
      vaccine strategies since they have better-defined mechanisms of action. In this
      article, we review several compounds that target specific immune components, such
      as cells, receptors or signaling pathways, and have termed such reagents 'smart
      adjuvants'.

PMID- 17542755
TI  - Implication of nanoparticles/microparticles in mucosal vaccine delivery.
AB  - Although polymeric nanoparticles/microparticles are well established for the
      mucosal administration of conventional drugs, they have not yet been developed
      commercially for vaccine delivery. The limitation of the mucosal (particularly
      oral) route of delivery, including low pH, gastric enzymes, rapid transit and
      poor absorption of large molecules, has made mucosal vaccine delivery
      challenging. Nevertheless, several polymeric delivery systems for mucosal vaccine
      delivery are currently being evaluated. The polymer-based approaches are designed
      to protect the antigen in the gut, to target the antigen to the gut-associated
      lymphoid tissue or to increase the residence time of the antigen in the gut
      through bioadhesion. M-cell targeting is a potential approach for mucosal vaccine
      delivery, which can be achieved using M-cell-specific lectins, microbial adhesins
      or immunoglobulins. While many hurdles must be overcome before targeted mucosal
      vaccine delivery becomes a practical reality, this is a potential area of
      research that has important implications for future vaccine development. This
      review comprises various aspects that could be decisive in the development of
      polymer based mucosal vaccine delivery systems.

PMID- 17542756
TI  - Intranasal vaccines for protection against respiratory and systemic bacterial
      infections.
AB  - More than 4 million deaths per year are due to respiratory diseases. Although
      licensed vaccines are available, bacteria, such as Streptococcus pneumoniae,
      Haemophilus influenzae, Mycobacterium tuberculosis, Bordetella pertussis and
      Neisseria meningiditis, among others, continue to be the major agents of diseases
      in young children, the elderly and/or immunocompromized individuals. Following
      respiratory tract infection, some microorganisms may also invade the epithelial
      tissue, achieving systemic circulation and/or other organs. Nasal administration
      of different antigen formulations has shown promising results in the induction of
      immune responses and the defeat of the pathogens at the site of infection. This
      review will focus on the main nasal vaccine strategies and technologies being
      investigated against the most common infections caused by respiratory bacteria.

PMID- 17542757
TI  - Live-attenuated Salmonella as a prototype vaccine vector for passenger immunogens
      in humans: are we there yet?
AB  - It has been nearly 20 years since the first Phase I clinical trial of a live
      attenuated bacterial vaccine was created by recombinant DNA methods, opening the
      door to the use of these organisms as mucosal delivery vehicles for passenger
      antigens. Over this time, a number of animal studies have indicated the
      feasibility of this approach. These include studies showing that bacteria can
      deliver antigens expressed by the bacterium itself and that bacteria can deliver
      DNA vaccines to be expressed in target eukaryotic cells. Concomitant studies have
      identified a number of attenuating mutations that render the bacterial vectors
      both safe and immunogenic in humans. Both avenues of research indicate the
      significant promise of this approach to mucosal vaccine development; however,
      this promise remains largely unrealized at the level of human clinical trials.
      This review sketches the history of this problem and points toward possible
      solutions using Salmonella vaccine vectors as the prototypes.

PMID- 17542759
TI  - Automated mass immunization of poultry: the prospect for nonreplicating human
      adenovirus-vectored in ovo vaccines.
AB  - Automated in ovo vaccination is an efficient method for mass immunization of
      poultry. Although in ovo vaccination has been used to mass immunize chickens
      against several infectious diseases, there are common poultry diseases for which
      in ovo-compatible vaccines are not commercially available. It was recently
      demonstrated that in ovo administration of a nonreplicating human adenovirus
      vector encoding an avian influenza virus hemagglutinin induced protective
      immunity against highly pathogenic avian influenza. The advantages of this new
      class of poultry vaccine include in ovo delivery of a wide variety of pathogen
      derived antigens, high potency in a single-dose regimen, rapid production in
      response to increased demand, no replication of the vector, no pre-existing
      immunity to human adenovirus in chickens, compatibility with automated in ovo
      administration and no interference with epidemiological surveys of natural
      infections.

PMID- 17542758
TI  - Next generation: tuberculosis vaccines that elicit protective CD8+ T cells.
AB  - Tuberculosis continues to cause considerable human morbidity and mortality
      worldwide, particularly in people coinfected with HIV. The emergence of multidrug
      resistance makes the medical treatment of tuberculosis even more difficult. Thus,
      the development of a tuberculosis vaccine is a global health priority. Here we
      review the data concerning the role of CD8+ T cells in immunity to tuberculosis
      and consider how CD8+ T cells can be elicited by vaccination. Many immunization
      strategies have the potential to elicit CD8+ T cells and we critically review the
      data supporting a role for vaccine-induced CD8+ T cells in protective immunity.
      The synergy between CD4+ and CD8+ T cells suggests that a vaccine that elicits
      both T-cell subsets has the best chance at preventing tuberculosis.

PMID- 17542760
TI  - Two-year changes in bone mineral density and T scores in patients treated at a
      pharmacist-run teriparatide clinic.
AB  - STUDY OBJECTIVES: To determine changes in bone mineral density (BMD) and T scores
      of patients after 2 years of teriparatide therapy, and to determine the number of
      fractures that occurred during therapy. DESIGN: Prospective, observational study.
      SETTING: Pharmacist-run teriparatide clinic in a private-practice endocrinology
      group. PATIENTS: Sixty patients with osteoporosis who experienced fractures or
      adverse events while receiving antiresorptive therapy and were referred by the
      endocrinologists to the clinic between January 1, 2002, and January 1, 2004.
      INTERVENTION: After a 1-hour counseling and training session with a clinical
      pharmacist, patients self-administered subcutaneous teriparatide 20 microg/day
      for the next 2 years. MEASUREMENTS AND MAIN RESULTS: Primary outcome measures
      were dual x-ray absorptiometry-determined BMDs and T scores for the total hip,
      spine, and wrist at baseline and at 1 and 2 years. Patients' BMDs for the hip
      significantly increased by 3.5% at 1 year and by 3.9% at 2 years. In addition,
      BMD for the spine significantly increased by 7.2% at 1 year and 10.9% at 2 years.
      In 56 (93%) patients, BMD for the spine increased after 2 years of treatment. For
      the wrist, BMD decreased by 0.75% at 1 year and by 2.4% at 2 years, but the
      change was only significant at 2 years (p=0.011). At both 1 and 2 years, T scores
      for the total hip and spine significantly improved from baseline (p< or =0.019),
      whereas T scores for the wrist significantly declined after 2 years of therapy
      (p<0.003). No new fractures were documented in any of the patients. CONCLUSION:
      In patients with osteoporosis, the use of teriparatide in a pharmacist-run clinic
      significantly increased BMD at the total hip and spinal sites and significantly
      decreased BMD in the wrist.

PMID- 17542761
TI  - Effects of long-term 4-aminopyridine therapy on glucose tolerance and
      glucokinetics in patients with spinal cord injury.
AB  - STUDY OBJECTIVE: To assess the effects of the potassium channel blocker, 4
      aminopyridine, on glucose tolerance and glucokinetics in patients with spinal
      cord injury. DESIGN: Prospective, dose level-blinded study. SETTING: University
      affiliated, tertiary-level care, Veterans Affairs medical center, and a
      university-affiliated research center. PATIENTS: Thirty-one patients with spinal
      cord injury of more than 1 year's duration. INTERVENTION: In a fasting state,
      patients ingested 75 g of glucose and completed a 5-hour oral glucose tolerance
      test before and after 6 months of treatment with an oral, immediate-release
      formulation of 4-aminopyridine. MEASUREMENTS AND MAIN RESULTS: The time course of
      glucose plasma concentrations during the oral glucose tolerance tests was
      profiled for each patient, and glucokinetic parameters were estimated. Results
      were compared at baseline and after 6 months of treatment with 4-aminopyridine.
      Of the 31 patients, 29 (94%) had impaired glucose tolerance at baseline. After 6
      months of treatment with 4-aminopyridine, 12 (41%) of the 29 patients had a 2
      hour postprandial glucose level that no longer supported a diagnosis of impaired
      glucose tolerance. No significant changes or clinically important trends were
      seen in fasting blood glucose concentrations or in other glucokinetic parameters
      in these patients. CONCLUSIONS: The long-term administration of an oral,
      immediate-release formulation of 4-aminopyridine to patients with longstanding
      spinal cord injury was associated with readily discernible, potentially
      clinically significant improvements in glucose tolerance. Because impaired
      glucose tolerance is a common finding in patients with spinal cord injury, more
      research, including randomized controlled trials with large study populations, is
      warranted on this potential treatment.

PMID- 17542762
TI  - Clinical evaluation of the nelfinavir-rifabutin interaction in patients with
      tuberculosis and human immunodeficiency virus infection.
AB  - STUDY OBJECTIVE: To characterize the bidirectional interaction between twice
      daily nelfinavir and twice-weekly rifabutin and isoniazid in patients with
      tuberculosis and human immunodeficiency virus (HIV) infection. DESIGN:
      Prospective cohort study. SETTING: Three clinical research centers. PATIENTS:
      Seven patients with HIV-related tuberculosis. INTERVENTION: Rifabutin 300 mg and
      isoniazid 15 mg/kg (maximum dose 900 mg) twice/week were administered for at
      least 2 weeks during the continuation phase of tuberculosis treatment.
      Antiretroviral therapy with nelfinavir 1250 mg twice/day and two nucleoside
      reverse transcriptase inhibitors was then added. MEASUREMENTS AND MAIN RESULTS:
      Patients underwent blood sampling for pharmacokinetic analysis during the
      continuation phase of tuberculosis therapy and after a median of 21 days after
      the addition of antiretroviral treatment. When rifabutin was coadministered with
      nelfinavir, its area under the concentration-time curve from 0-21 hours (AUC(0
      21)) increased 22% (geometric mean 5.01 microg.hr/ml [90% confidence interval
      (CI) 3.25-7.71] with nelfinavir vs 4.10 microg.hr/ml [90% CI 3.18-5.27] without
      nelfinavir; geometric mean ratio 1.22 [90% CI 0.78-1.92]). Also, the AUC(0-21)
      for the active metabolite, desacetylrifabutin, increased significantly (geometric
      mean ratio 3.46, 90% CI 1.84-6.47, p=0.009). In the presence of rifabutin, the
      pharmacokinetic parameters of nelfinavir and its principal metabolite M8 were
      similar to those of patients not taking rifabutin. No drug interaction between
      nelfinavir and isoniazid was detected. CONCLUSIONS: Coadministration of rifabutin
      and isoniazid without dosage adjustment during twice-weekly tuberculosis therapy
      with nelfinavir-based antiretroviral therapy resulted in rifabutin exposures
      within the acceptable ranges for safety and efficacy. Therefore, this combination
      is an appropriate option for the simultaneous treatment of tuberculosis and HIV
      infection when tuberculosis therapy is given twice weekly.

PMID- 17542763
TI  - Association of beta-blocker dose with serum procollagen concentrations and
      cardiac response to spironolactone in patients with heart failure.
AB  - STUDY OBJECTIVE: To determine whether beta-blocker dose influences cardiac
      collagen turnover and the effects of spironolactone on cardiac collagen turnover
      in patients with heart failure. DESIGN: Prospective clinical study. SETTING: Two
      heart failure centers. PATIENTS: Eighty-eight spironolactone-naive patients with
      heart failure who were taking beta-blockers. INTERVENTION: In a subset of 29
      patients, spironolactone was started at 12.5 mg/day, with the dosage titrated to
      25 mg/day if tolerated. MEASUREMENTS AND MAIN RESULTS: Venous blood samples were
      collected from each patient. Serum procollagen type I and type III aminoterminal
      peptides (PINP and PIIINP) were determined by radioimmunoassay and compared
      between the 25 patients receiving low doses (< 50% of recommended target dose)
      and the 63 patients receiving high doses (> or = 50% of recommended target dose)
      of beta-blockers. Patients receiving low-dose beta-blockers had higher mean +/-
      SD PIIINP concentrations (6.6 +/- 3.5 vs 4.9 +/- 2.6 microg/L, p=0.03) and tended
      to have higher PINP concentrations (74.0 +/- 44.1 vs 57.1 +/- 28.6 microg/L,
      p=0.10) compared with those receiving high doses. A repeat blood sample was
      collected from the 29 patients who received spironolactone after 6 months of
      therapy. Changes in procollagen peptides also were compared in this subset
      between low-dose (9 patients) and high-dose (20 patients) beta-blocker groups.
      Low beta-blocker doses were associated with greater reductions in concentrations
      of PINP (median [intraquartile range] -14.3 microg/L [-9.8 to -19.3 microg/L] vs 
      2.5 microg/L [5.9 to -9.8 microg/L], p=0.02) and PIIINP (-1.4 microg/L [-0.9 to 
      2.4 microg/L] vs 0.1 microg/L [0.9 to -1.3 microg/L], p=0.045) with
      spironolactone therapy than high beta-blocker doses. In addition, 100% of the
      patients in this subset taking low-dose beta-blockers versus only 35% taking
      higher doses had reductions in both markers of cardiac fibrosis. CONCLUSION:
      Spironolactone may benefit patients with heart failure who cannot tolerate upward
      titration of beta-blocker dosages, at least in terms of its effects on cardiac
      remodeling.

PMID- 17542764
TI  - Peginterferon alfa-2a versus peginterferon alfa-2b as initial treatment of
      hepatitis C virus infection: a cost-utility analysis from the perspective of the
      Veterans Affairs Health Care System.
AB  - STUDY OBJECTIVE: To assess the cost-utility of peginterferon alfa-2a plus
      ribavirin, peginterferon alfa-2b plus ribavirin, and no therapy for treatment
      naive patients with chronic hepatitis C virus (HCV) infection from the
      perspective of the Veterans Affairs (VA) health care system by using patient
      reported utility scores. DESIGN: Cost-utility analysis using a Markov model.
      SETTING: Veterans Affairs health care system. DATA SOURCE: Data for the model
      were obtained from clinical trials and published literature. Data from the VA
      health care system were used to define the patient cohorts. MEASUREMENTS AND MAIN
      RESULTS: A Markov model incorporating transition probabilities between disease
      health states that depend only on the current health state was developed to
      simulate the progression of HCV disease. The patient cohorts were a 45-year-old
      male cohort and a 55-year-old male cohort, each with liver fibrosis but no
      cirrhosis. The lifetime expected costs, quality-adjusted life-years (QALYs)
      gained, and incremental net monetary benefit (INMB) with HCV treatments were
      determined for each cohort by genotype (genotype 1, and genotypes 2 and 3). Both
      peginterferon regimens were significantly more cost-effective than no treatment,
      although no significant differences in costs or QALYs were noted between
      peginterferon regimens. For the 45-year-old cohort with a genotype 1 infection,
      the INMB was $128,583 (95% confidence interval [CI] $79,279-$177,308) and
      $128,025 (95% CI $80,425-$173,448) versus no treatment for peginterferon alfa-2a
      plus ribavirin and peginterferon alfa-2b plus ribavirin, respectively. Treatment
      with either peginterferon regimen produced significantly lower lifetime HCV
      related medical costs for genotype 2 or 3 infections, but not genotype 1.
      CONCLUSIONS: Peginterferon alfa-2a plus ribavirin and peginterferon alfa-2b plus
      ribavirin were found to be cost-effective treatments for patients with HCV
      infections, particularly with genotypes 2 and 3. However, no significant
      differences in costs or efficacy were observed between these peginterferon
      treatment regimens.

PMID- 17542765
TI  - Effect of oral posaconazole on the pharmacokinetics of cyclosporine and
      tacrolimus.
AB  - STUDY OBJECTIVE: To analyze the pharmacokinetic properties of the
      immunosuppressants cyclosporine and tacrolimus when either is coadministered with
      oral posaconazole. DESIGN: Two single-center, open-label pharmacokinetic studies
      of cyclosporine in a multiple-dose design and of tacrolimus in a one-sequence,
      crossover, single- and multiple-dose design. SETTING: One clinical investigative
      center in the United States and one in the United Kingdom. SUBJECTS: Four adult
      heart transplant recipients in the cyclosporine study and 36 healthy adult
      volunteers in the tacrolimus study. INTERVENTIONS: In the cyclosporine study,
      patients who took an established cyclosporine dose 3 times/day for 6 weeks or
      longer were given posaconazole 200 mg/day for 10 days. In the tacrolimus study,
      subjects received tacrolimus 0.05 mg/kg/day on days 1 and 14 and posaconazole 400
      mg twice/day on days 7-14. MEASUREMENTS AND MAIN RESULTS: In the cyclosporine
      study, blood samples were collected on day 1 to determine cyclosporine
      pharmacokinetics and on day 10 to measure the pharmacokinetics of cyclosporine
      and posaconazole. Coadministration of posaconazole increased cyclosporine
      exposure and necessitated dosage reductions of 14-29% for cyclosporine in three
      subjects. In the tacrolimus study, blood samples were collected on days 12-14 to
      assess posaconazole pharmacokinetics and on days 1 and 14 for as long 72 hours
      after dosing to evaluate tacrolimus pharmacokinetics. Posaconazole increased the
      maximum blood concentration and the area under the concentration-time curve for
      tacrolimus by 121% and 358%, respectively, on day 14 compared with day 1 (both
      p=0.001). In both studies, posaconazole pharmacokinetics were unaffected.
      CONCLUSION: These findings suggest that the dosage of cyclosporine or tacrolimus
      should be reduced when posaconazole therapy is started and that plasma levels of
      the immunosuppressant should be monitored during and at the discontinuation of
      posaconazole therapy so that dosages are adjusted accordingly. This
      recommendation is consistent with current standard of care for patients receiving
      cyclosporine or tacrolimus with concomitant azole antifungal therapy.

PMID- 17542766
TI  - Absence of an interaction between tigecycline and digoxin in healthy men.
AB  - STUDY OBJECTIVE: To evaluate a potential interaction between tigecycline and
      digoxin using pharmacokinetic and pharmacodynamic assessments. DESIGN: Open
      label, three-period, one-sequence crossover study. SETTING: Hospital-affiliated,
      inpatient clinical pharmacology unit. SUBJECTS: Twenty healthy men. INTERVENTION:
      Tigecycline 100 mg was administered intravenously as a single dose on day 1
      (period 1). Digoxin was administered as a 0.5-mg oral loading dose on day 7,
      followed by 0.25 mg/day on days 8-14 (period 2). Digoxin 0.25 mg/day was
      continued on days 15-19; in addition, on day 15, a loading dose of tigecycline
      100 mg was administered intravenously, followed by 50 mg every 12 hours starting
      on the evening of day 15 through the morning of day 19 (period 3). MEASUREMENTS
      AND MAIN RESULTS: Pharmacokinetic assessments were performed on days 1 and 19 for
      tigecycline and on days 14 and 19 for digoxin. Electrocardiographic parameters
      were measured at baseline and on days 1, 14, and 19 to assess digoxin
      pharmacodynamics. Serum tigecycline concentrations were determined by liquid
      chromatography with tandem mass spectrometry detection, and plasma and urine
      digoxin concentrations were determined by radioimmunoassay. Tigecycline area
      under the concentration-time curve (AUC), AUC from 0-12 hours (AUC(0-12)), weight
      normalized clearance, and mean resistance time were not affected by concomitant
      multiple-dose digoxin administration, but tigecycline half-life was decreased
      during period 1, apparently due to fewer detectable terminal concentrations in
      some subjects. Digoxin steady-state AUC(0-24), weight-normalized oral dose
      clearance, cumulative amount of drug excreted in urine over 24 hours, renal
      clearance, and QTc (change from baseline) were not affected by multiple-dose
      tigecycline administration. CONCLUSION: No significant effects of tigecycline on
      digoxin pharmacokinetics and pharmacodynamics were noted, but a small effect of
      digoxin on tigecycline pharmacokinetics cannot be ruled out due to design issues
      with period 1 of the study.

PMID- 17542767
TI  - Effectiveness and hepatotoxicity of statins in men seropositive for hepatitis C
      virus.
AB  - STUDY OBJECTIVE: To evaluate the effectiveness and hepatotoxicity of statins in
      patients who are seropositive for hepatitis C virus (HCV). DESIGN: Retrospective
      review of a registry of patients with HCV. SETTING: Veterans Affairs Medical
      Center. PATIENTS: One hundred forty-six male patients who were seropositive for
      HCV and had received statin therapy between January 1, 1995, and September 9,
      2003. MEASUREMENTS AND MAIN RESULTS: Demographic and clinical data were collected
      for each patient; lipid and alanine aminotransferase (ALT) levels at baseline
      (within 6 mo of starting a statin), at 3 and 6 months after starting a statin,
      and at long-term follow-up (mean 22 mo) were also recorded. The primary efficacy
      end point was a significant decrease from baseline to long-term follow-up low
      density lipoprotein cholesterol (LDL) level; the primary safety end point was a
      significant increase from baseline in ALT level. The mean change in LDL level was
      a reduction of 22% (p<0.01). No significant increases in ALT levels were
      observed; only one patient discontinued therapy due to ALT level elevations
      greater than 3 times the upper limit of normal. CONCLUSION: In men seropositive
      for HCV, statins were effective in reducing LDL levels and did not result in
      significant increases in ALT levels from baseline. Thus, statin therapy should be
      considered for patients with HCV who are at risk for coronary heart disease and
      do not have significantly elevated serum transaminase levels at baseline.

PMID- 17542768
TI  - Meta-analysis of azelastine nasal spray for the treatment of allergic rhinitis.
AB  - STUDY OBJECTIVE: To systematically review the efficacy of azelastine nasal spray
      for the treatment of allergic rhinitis. DESIGN: Meta-analysis of published
      randomized controlled trials reported in English. DATA SOURCE: Published
      literature from the PubMed-MEDLINE database. PATIENTS: Patients aged at least 12
      (United States) or 16 years (Europe) with allergic rhinitis or nonallergic
      vasomotor rhinitis. MEASUREMENTS AND MAIN RESULTS: A global assessment of
      efficacy was used to estimate the number needed to treat for azelastine nasal
      spray compared with placebo or active comparators. The total symptom score was
      used to compare the effect size between azelastine and placebo. In five
      comparisons of azelastine and placebo, azelastine was most efficacious, with a
      summary number needed to treat of 5.0 (95% confidence interval [CI] 3.3-10.0). In
      reviewing 11 studies of azelastine versus active comparators, we found no
      significant difference between azelastine and active comparators (number needed
      to treat 66.7, 95% CI 14.3 to infinity to 25). Azelastine was more efficacious
      than placebo in terms of total symptom score (effect size of 0.36, 95% CI 0.26
      0.46). CONCLUSION: Azelastine nasal spray was more efficacious than placebo in
      the treatment of allergic rhinitis. No significant differences were observed
      between azelastine and active comparators for the treatment of allergic rhinitis;
      however, when azelastine was compared with oral antihistamines as monotherapy,
      the trend favored azelastine. Because azelastine appears to be as efficacious as
      oral antihistamines, the choice of treatment for seasonal allergic rhinitis
      should depend on the patient's preference regarding the route of administration,
      adverse effects, and the cost of the drug.

PMID- 17542769
TI  - Emerging role of anticoagulants and fibrinolytics in the treatment of acute
      respiratory distress syndrome.
AB  - Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are
      associated with high mortality rates despite therapeutic advances. The
      pathogenesis of ALI and ARDS is similar to that of sepsis, as these disease
      states involve uncontrolled host defense responses that lead to inflammation,
      endothelial damage, enhanced coagulation, diminished fibrinolysis, and
      fibroproliferation. Recent studies of anticoagulants have shown positive outcomes
      in patients with severe sepsis. In addition, emerging evidence suggests that the
      use of anticoagulants, such as tissue factor pathway inhibitor, antithrombin,
      thrombomodulin, heparin, activated protein C, and fibrinolytics (plasminogen
      activators and particularly tissue plasminogen activator), may be useful in the
      treatment of ALI and ARDS. Data from experimental models of sepsis, ALI, and ARDS
      indicate that some of these agents improve lung function and oxygenation.
      Although clinical data are less convincing than these findings, results from
      clinical trials may influence the design of future studies.

PMID- 17542770
TI  - Pharmacogenetics of beta-blockers.
AB  - Beta-blockers are an important cardiovascular drug class, recommended as first
      line treatment of numerous diseases such as heart failure, hypertension, and
      angina, as well as treatment after myocardial infarction. However, responses to a
      beta-blocker are variable among patients. Results of numerous studies now suggest
      that genetic polymorphisms may contribute to variability in responses to beta
      blockers. This review summarizes the pharmacogenetic data for beta-blockers in
      patients with various diseases and discusses the potential implications of beta
      blocker pharmacogenetics in clinical practice.

PMID- 17542771
TI  - Mechanisms of pharmacokinetic and pharmacodynamic drug interactions associated
      with ritonavir-enhanced tipranavir.
AB  - Tipranavir is a nonpeptidic protease inhibitor that has activity against human
      immunodeficiency virus strains resistant to multiple protease inhibitors.
      Tipranavir 500 mg is coadministered with ritonavir 200 mg. Tipranavir is
      metabolized by cytochrome P450 (CYP) 3A and, when combined with ritonavir in
      vitro, causes inhibition of CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A in
      addition to induction of glucuronidase and the drug transporter P-glycoprotein.
      As a result, drug-drug interactions between tipranavir-ritonavir and other
      coadministered drugs are a concern. In addition to interactions with other
      antiretrovirals, tipranavir-ritonavir interactions with antifungals,
      antimycobacterials, oral contraceptives, statins, and antidiarrheals have been
      specifically evaluated. For other drugs such as antiarrhythmics, antihistamines,
      ergot derivatives, selective serotonin receptor agonists (or triptans),
      gastrointestinal motility agents, erectile dysfunction agents, and calcium
      channel blockers, interactions can be predicted based on studies with other
      ritonavir-boosted protease inhibitors and what is known about tipranavir
      ritonavir CYP and P-glycoprotein utilization. The highly complex nature of drug
      interactions dictates that cautious prescribing should occur with narrow
      therapeutic-index drugs that have not been specifically studied. Thus, the known
      interaction potential of tipranavir-ritonavir is reported, and in vitro and in
      vivo data are provided to assist clinicians in predicting interactions not yet
      studied. As more clinical interaction data are generated, better insight will be
      gained into the specific mechanisms of interactions with tipranavir-ritonavir.

PMID- 17542772
TI  - Pancreatic enzyme pharmacotherapy.
AB  - Supplemental pancreatic enzyme preparations are provided to patients with
      conditions of pancreatic exocrine deficiency such as chronic pancreatitis and
      cystic fibrosis. These patients frequently experience steatorrhea, which occurs
      from inadequate fat absorption. The delivery of sufficient enzyme concentrations
      into the duodenal lumen simultaneously with meals can reduce nutrient
      malabsorption, improve the symptoms of steatorrhea, and in some cases alleviate
      the pain associated with chronic pancreatitis. Current clinical practices dictate
      administration of lipase 25,000-40,000 units/meal by using pH-sensitive
      pancrelipase microspheres, along with dosage increases, compliance checks, and
      differential diagnosis in cases of treatment failure. Despite the large number of
      specialty enzyme replacements available commercially, many patients remain
      dissatisfied with standard therapy, and future developments are needed to
      optimize treatment in these individuals.

PMID- 17542773
TI  - Fondaparinux as a treatment option for heparin-induced thrombocytopenia.
AB  - Heparin-induced thrombocytopenia (HIT) is an immune-mediated complication that
      can occur after exposure to heparin products. Because patients with HIT are at
      increased risk for thrombosis, anticoagulation is warranted. The direct thrombin
      inhibitors lepirudin and argatroban are approved by the United States Food and
      Drug Administration (FDA) for this indication. Bivalirudin, another direct
      thrombin inhibitor, is approved for use in patients with HIT who must undergo
      percutaneous coronary intervention. The synthetic pentasaccharide fondaparinux
      lacks FDA approval for treating patients with HIT; however, a few published
      reports describe its use. Furthermore, various small-scale, in vitro studies have
      demonstrated a lack of cross-reactivity between fondaparinux and HIT antibodies.
      Large, in vivo comparison trials must be performed before fondaparinux can become
      a standard treatment option in the setting of HIT.

PMID- 17542774
TI  - A febrile neutropenic patient with Enterococcus gallinarum sepsis treated with
      daptomycin and gentamicin.
AB  - Gram-positive pathogens are increasingly implicated in today's changing
      epidemiology of hospital-acquired infections. Staphylococci, streptococci, and
      enterococci are among the most frequently identified causes of surgical site,
      complicated skin-structure, and bloodstream infections. In accordance, the use of
      antimicrobial agents with gram-positive activity, especially those with activity
      against resistant organisms, has also increased. We describe a septic,
      neutropenic patient with bacteremia due to Enterococcus gallinarum. Therapeutic
      options were restricted due to resistance factors of the organism, limited
      guidance in the medical literature, and the patient's history and underlying
      condition. Despite these challenges, the patient was successfully treated with a
      combination of daptomycin and gentamicin and replacement of her indwelling
      central line. As antimicrobial stewards and diagnosticians, we must bear in mind
      that selective pressures exerted by the increasing use of agents with gram
      positive activity may result in an increased prevalence of organisms such as E.
      gallinarum.

PMID- 17542775
TI  - Intravenous warfarin as an alternative for anticoagulation.
AB  - Oral warfarin is the standard of care for patients requiring long-term
      anticoagulation due to venous thromboembolic disease. Patients with Crohn's
      disease may have reduced absorption in the small bowel due to loss of effective
      surface area secondary to chronic inflammation, ulcerative lesions, or resection.
      A 27-year-old Caucasian woman with end-stage Crohn's disease was hospitalized
      with an upper extremity thrombosis. In this complicated patient, who was
      resistant to oral warfarin and unable to receive subcutaneous low-molecular
      weight heparin, therapeutic anticoagulation was achieved with intravenous
      warfarin. Intravenous warfarin provides an alternative administration route for
      patients who cannot receive the oral formulation and cannot be administered
      subcutaneous low-molecular-weight heparins due to adverse effects.

PMID- 17542776
TI  - Inference on the limiting false discovery rate and the p-value threshold
      parameter assuming weak dependence between gene expression levels within subject.
AB  - An objective of microarray data analysis is to identify gene expressions that are
      associated with a disease related outcome. For each gene, a test statistic is
      computed to determine if an association exists, and this statistic generates a
      marginal p-value. In an effort to pool this information across genes, a p-value
      density function is derived. The p-value density is modeled as a mixture of a
      uniform (0,1) density and a scaled ratio of normal densities derived from the
      asymptotic normality of the test statistic. The p-values are assumed to be weakly
      dependent and a quasi-likelihood is used to estimate the parameters in the
      mixture density. The quasi-likelihood and the weak dependence assumption enables
      estimation and asymptotic inference on the false discovery rate for a given
      rejection region, and its inverse, the p-value threshold parameter for a fixed
      false discovery rate. A false discovery rate analysis on a localized prostate
      cancer data set is used to illustrate the methodology. Simulations are performed
      to assess the performance of this methodology.

PMID- 17542777
TI  - Reconstructing gene regulatory networks with bayesian networks by combining
      expression data with multiple sources of prior knowledge.
AB  - There have been various attempts to reconstruct gene regulatory networks from
      microarray expression data in the past. However, owing to the limited amount of
      independent experimental conditions and noise inherent in the measurements, the
      results have been rather modest so far. For this reason it seems advisable to
      include biological prior knowledge, related, for instance, to transcription
      factor binding locations in promoter regions or partially known signalling
      pathways from the literature. In the present paper, we consider a Bayesian
      approach to systematically integrate expression data with multiple sources of
      prior knowledge. Each source is encoded via a separate energy function, from
      which a prior distribution over network structures in the form of a Gibbs
      distribution is constructed. The hyperparameters associated with the different
      sources of prior knowledge, which measure the influence of the respective prior
      relative to the data, are sampled from the posterior distribution with MCMC. We
      have evaluated the proposed scheme on the yeast cell cycle and the Raf signalling
      pathway. Our findings quantify to what extent the inclusion of independent prior
      knowledge improves the network reconstruction accuracy, and the values of the
      hyperparameters inferred with the proposed scheme were found to be close to
      optimal with respect to minimizing the reconstruction error.

PMID- 17542778
TI  - Cox survival analysis of microarray gene expression data using correlation
      principal component regression.
AB  - Statistical analysis of microarray gene expression data has recently attracted a
      great deal of attention. One problem of interest is to relate genes to survival
      outcomes of patients with the purpose of building regression models for the
      prediction of future patients' survival based on their gene expression data. For
      this, several authors have discussed the use of the proportional hazards or Cox
      model after reducing the dimension of the gene expression data. This paper
      presents a new approach to conduct the Cox survival analysis of microarray gene
      expression data with the focus on models' predictive ability. The method modifies
      the correlation principal component regression (Sun, 1995) to handle the
      censoring problem of survival data. The results based on simulated data and a set
      of publicly available data on diffuse large B-cell lymphoma show that the
      proposed method works well in terms of models' robustness and predictive ability
      in comparison with some existing partial least squares approaches. Also, the new
      approach is simpler and easy to implement.

PMID- 17542779
TI  - The experiences of Irish nurse lecturers role transition from clinician to
      educator.
AB  - Described in this study are the experiences of six clinical nurses in Ireland who
      have transitioned to the role of nurse lecturer. Semi-structured interviews were
      used to gather data from these novice nurse lecturers. Data were analyzed
      manually and thematically, generating five emerging themes: feelings experienced
      during the transition; educational preparation for the role; actual and potential
      support structures available; hindering factors of the role; and the overall
      transition experience. Negative feelings and experiences encountered were found
      to decrease as participants accepted their role change, gained experience in
      their new role, and became more familiar with their work environment.

PMID- 17542780
TI  - Morphine inhibits doxorubicin-induced reactive oxygen species generation and
      nuclear factor kappaB transcriptional activation in neuroblastoma SH-SY5Y cells.
AB  - Morphine is recommended as a first-line opioid analgesic in the pain management
      of cancer patients. Accumulating evidence shows that morphine has anti-apoptotic
      activity, but its impact on the therapeutic applications of antineoplastic drugs
      is not well known. The present study was undertaken to test the hypothesis that
      morphine might antagonize the pro-apoptotic activity of DOX (doxorubicin), a
      commonly used antitumour drug for the treatment of neuroblastoma, in cultured SH
      SY5Y cells. In the present study we demonstrated that morphine suppressed DOX
      induced inhibition of cell proliferation and programmed cell death in a
      concentration-dependent, and naloxone as well as pertussis toxin-irreversible,
      manner. Further studies showed that morphine inhibited ROS (reactive oxygen
      species) generation, and prevented DOX-mediated caspase-3 activation, cytochrome
      c release and changes of Bax and Bcl-2 protein expression. The antioxidant NAC (N
      acetylcysteine) also showed the same effects as morphine on DOX-induced ROS
      generation, caspase-3 activation and cytochrome c release and changes in Bax (Bcl
      2-associated X protein) and Bcl-2 protein expression. Additionally, morphine was
      found to suppress DOX-induced NF-kappaB (nuclear factor kappaB) transcriptional
      activation via a reduction of IkappaBalpha (inhibitor of nuclear factor kappaB)
      degradation. These present findings support the hypothesis that morphine can
      inhibit DOX-induced neuroblastoma cell apoptosis by the inhibition of ROS
      generation and mitochondrial cytochrome c release, as well as by blockade of NF
      kappaB transcriptional activation, and suggests that morphine might have an
      impact on the antitumour efficiency of DOX.

PMID- 17542781
TI  - Structural and functional differences among human surfactant proteins SP-A1, SP
      A2 and co-expressed SP-A1/SP-A2: role of supratrimeric oligomerization.
AB  - SP-A (surfactant protein A) is a membrane-associated SP that helps to maintain
      the lung in a sterile and non-inflamed state. Unlike SP-As from other mammalian
      species, human SP-A consists of two functional gene products: SP-A1 and SP-A2. In
      all the functions examined, recombinant human SP-A1 invariably exhibits lower
      biological activity than SP-A2. The objective of the present study was to
      investigate why SP-A2 possesses greater biological activity than SP-A1 and what
      advantage accrues to having two polypeptide chains instead of one. We analysed
      structural and functional characteristics of recombinant baculovirus-derived SP
      A1, SP-A2 and co-expressed SP-A1/SP-A2 using a wide array of experimental
      approaches such as analytical ultracentrifugation, DSC (differential scanning
      calorimetry) and fluorescence. We found that the extent of supratrimeric assembly
      is much lower in SP-A1 than SP-A2. However, the resistance to proteolysis is
      greater for SP-A1 than for SP-A2. Co-expressed SP-A1/SP-A2 had greater thermal
      stability than SP-A1 and SP-A2 and exhibited properties of each protein. On the
      one hand, SP-A1/SP-A2, like SP-A2, had a higher degree of oligomerization than SP
      A1, and consequently had lower K(d) for binding to bacterial Re-LPS (rough
      lipopolysaccharide), higher self-association in the presence of calcium and
      greater capability to aggregate Re-LPS and phospholipids than SP-A1. On the other
      hand, SP-A1/SP-A2, like SP-A1, was more resistant to trypsin degradation than SP
      A2. Finally, the importance of the supratrimeric assembly for SP-A
      immunomodulatory function is discussed.

PMID- 17542782
TI  - Global longitudinal strain by two-dimensional speckle tracking echocardiography
      is closely related to myocardial infarct size in chronic ischaemic heart disease.

PMID- 17542784
TI  - Establishing a rural academic infrastructure for individual health professions.

PMID- 17542785
TI  - Growing old and getting sick: maintaining a positive spirit at the end of life.
AB  - End of life throws up significant mental health challenges. A high proportion of
      people in the terminal stages of illness experience depressive symptoms. This
      paper integrates a theory of hierarchy of human needs and empirical research
      describing experiences of grief and depression in terminal illness, to develop a
      model of care aimed at reducing depression and suffering. This care attends to
      physical, psychological, social and spiritual aspects, taking into account the
      concerns of patients and their families. Professional help can be offered to
      patients to restore dignity and hope, strengthen their ways of coping, and
      encourage social connections. To offer this, a well-resourced and coordinated,
      multidisciplinary and skilled workforce is needed.

PMID- 17542786
TI  - Building sustainable rural research capacity: the experiences of a brain injury
      rehabilitation service.
AB  - There is an emerging recognition of the need for health research that is
      conducted by and for rural people. Rural research promotes excellence in clinical
      practice and can improve staff recruitment and retention. A group of clinicians
      from a regional brain injury service collaborated with academics at their local
      university to form the Rural Rehabilitation Research on Brain Injury initiative.
      This initiative has funded four peer-reviewed research projects, secured an
      Australian Research Council grant and established the beginnings of a state-wide
      rural research collective involving all Brain Injury Rehabilitation Programs in
      New South Wales. Sustainable research enterprises such as this have significant
      potential as a 'prototype' for building research capacity in other rural health
      sectors. Governments and funding bodies should support these initiatives.

PMID- 17542787
TI  - Evaluation of the national pharmacy preceptor education program.
AB  - OBJECTIVE: The process evaluation findings and key issues from a trial of the
      effectiveness and national applicability of a national online educational
      curriculum for pharmacist preceptors are presented. DESIGN: A multi-method
      triangulated research design was used to elicit qualitative and quantitative data
      preceptors. The data collection method involved an anonymous questionnaire with
      both quantitative components and open-ended qualitative responses. SETTING: An
      online education program for preceptors of Australian pharmacy students in rural
      areas. PARTICIPANTS: Rural pharmacists in the three states were invited to trial
      the package and participate in the associated research/evaluation project. MAIN
      OUTCOME MEASURES: The Australian Pharmacy Preceptor Education (APPE) program is
      an important and valuable educational tool for the professional development of
      pharmacists. It contained pertinent information and appropriate activities, and
      the delivery strategy was well accepted. The evaluation findings support a
      national implementation. RESULTS: Program strengths include the ease of access,
      self-directed learning and the interactive nature emphasising the benefit of
      sharing ideas and feedback. Potential program limitations include technical
      delays and unclear instructions for undertaking the program. CONCLUSION: The
      online APPE program is a flexible delivery strategy which has the potential to
      dramatically improve the skills and knowledge of pharmacists acting as preceptors
      and, thereby, impact on the learning provided in rural hospitals and community
      pharmacies for undergraduate students and new graduates alike.

PMID- 17542788
TI  - Can a rural community-based work-related activity program make a difference for
      chronic pain-disabled injured workers?
AB  - OBJECTIVE: To assess the effectiveness of a clinical guidelines-informed
      multidisciplinary work-related activity program, and to improve the physical,
      psychological and occupational functioning of chronic pain-disabled injured
      workers. DESIGN: An uncontrolled, repeated-measures, pilot study was conducted.
      SETTING: The intervention was delivered in a community setting in regional New
      South Wales. PARTICIPANTS: Participants (n = 30), mean age of 41 years, had a
      compensable musculoskeletal injury: 60% were male, 63% had back injuries; the
      mean time off work was 13 months. INTERVENTION: A cognitive-behavioural,
      interdisciplinary intervention was delivered using a multi-contributor provider
      model (a clinical psychologist and physiotherapist from separate practices,
      working in liaison with the participant's occupational rehabilitation provider
      and treating doctor). Groups of six participants attended for one half day per
      week for six weeks. MAIN OUTCOME MEASURES: The outcome measures included:
      physical functioning, pain intensity and psychological variables, which were
      assessed pre- and post-program; and medical certification and work participation,
      which was recorded pre-program and at six-month follow up. RESULTS: Significant
      gains were made in pain intensity, physical and psychological functioning, and
      medical certification. The mean effect size of the intervention was medium to
      large (d = 0.70). There was no significant change in employment status at six
      month follow up. CONCLUSIONS: The results of this pilot study suggest that
      independent, rural or community-based practitioners, working collaboratively
      using an integrated treatment program, can produce positive outcomes for pain
      disabled injured workers, and achieve results similar to those reported by
      metropolitan-based pain clinics.

PMID- 17542789
TI  - Benefits and challenges of providing transitional rehabilitation services to
      people with spinal cord injury from regional, rural and remote locations.
AB  - OBJECTIVE: To identify the factors influencing participation and outline the
      benefits and challenges of providing transitional rehabilitation for people with
      spinal cord injury (SCI) from rural and regional locations. DESIGN: Grounded
      Theory analysis of service records and policy documents. SETTING: One
      transitional rehabilitation service for people with SCI. PARTICIPANTS: Service
      records of 40 individuals with SCI from non-metropolitan locations who
      participated in transitional rehabilitation and 29 individuals with SCI who
      declined transitional rehabilitation over a two-year period. INTERVENTIONS: Home
      based transitional rehabilitation programs offered by a multidisciplinary team
      including physiotherapy, occupational therapy, nursing and social work. MEASURES:
      Participation was measured using the percentage of people from non-metropolitan
      locations who decline transitional rehabilitation. The benefits and challenges of
      transitional rehabilitation were identified using open, axial and selective
      coding of service records. RESULTS: People with SCI from non-metropolitan areas
      were underrepresented among transitional rehabilitation participants, with 69% of
      those declining transitional rehabilitation coming from regional or rural areas.
      The study identified five functions of transitional rehabilitation that presented
      both benefits and challenges of this model in assisting people from non
      metropolitan locations. These included: (1) the identification, education,
      coordination and funding of local care providers; (2) family involvement in
      rehabilitation; (3) contact with social and community supports; (4) specialist
      support to problem-solve discharge needs; and (5) skill acquisition and transfer
      in a community environment. CONCLUSIONS: The transitional rehabilitation model
      offers many advantages over traditional hospital-based rehabilitation but still
      faces challenges in offering an equitable model for people with SCI from non
      metropolitan locations.

PMID- 17542790
TI  - Junior medical officer recruitment: challenges and lessons from the Northern
      Territory.
AB  - OBJECTIVE: To examine the influence of newspaper and Internet advertising, word
      of-mouth endorsement and student experience in attracting applicants for junior
      medical officer positions in the Northern Territory. DESIGN: A retrospective
      study. PARTICIPANTS: Fifty-four applicants for junior medical officer positions.
      MAIN OUTCOME MEASURE: Proportion of applicants who reported newspaper
      advertising, Internet advertising, word of mouth or personal experience in
      attracting their application for an intern or resident medical officer position.
      RESULTS: Nineteen per cent of applicants saw the newspaper advertisement and 52%
      of the Internet advertisement. Eighty-seven per cent of applicants were
      influenced by word-of-mouth endorsement and 52% by student experience in the
      Northern Territory or Indigenous health. CONCLUSION: These results suggest that
      word-of-mouth endorsement has the greatest influence in attracting applicants for
      junior medical officer positions in Northern Territory hospitals.

PMID- 17542791
TI  - Diagnosing dementia in rural New South Wales.
AB  - OBJECTIVE: Review of dementia screening case profiles that included brain blood
      flow imaging to determine contribution to diagnosis. DESIGN: Retrospective
      medical case audit. SETTING: Rural New South Wales. PARTICIPANTS: Eighty-eight
      rural patients who underwent investigations for dementia diagnosis. MAIN OUTCOME
      MEASURE: Contribution of brain blood flow imaging (single photon emission
      tomography, SPECT) to the dementia screening regime. RESULTS: The age range of
      those referred was 21-88 years, the average being 70 years. There were 44 men and
      44 women. Vascular causes of dementia accounted for 27% of all those referred for
      brain blood imaging. Senile dementia of the Alzheimer's type accounted for 40% of
      all referrals. The occurrence of mixed disease was 6%. Matching
      neuropsychological reports and computer tomography were available for 18 of the
      blood flow studies. Of these, 65% were in agreement or semi-agreement for the
      diagnostic outcome. Only five studies failed to reach consensus. GPs were
      responsible for 31% of the imaging referrals, and the remaining referrals were
      from the regions: two gerontologists, three physicians and two neurologists.
      CONCLUSIONS: Brain blood flow imaging did contribute to the final diagnosis of
      dementia type for these patients, influencing patient management.

PMID- 17542792
TI  - Trends in private dental service provision in major city and other Australian
      locations.
AB  - OBJECTIVE: To investigate time trends in dental service provision by location.
      DESIGN: Five cross-sectional surveys across a 20-year period. SETTING: Australian
      private general dental practice. PARTICIPANTS: A random sample of dentists.
      METHODS: Mailed questionnaires were collected in 1983, 1988, 1993, 1998 and 2003
      (response rates 71-76%). MAIN OUTCOME MEASURES: Annual services per dentist.
      RESULTS: Decreases in the provision of restorative services, and increases in
      diagnostic and preventive services, occurred in major city locations but not in
      other locations. While decreases over time were observed in extraction rates in
      both major city and other locations, higher extraction rates persisted outside of
      major city locations. Denture and endodontic services fluctuated over time in
      both major city and other locations, with no difference by location observed in
      2003-2004. No changes over time were observed for crown and bridge services, but
      crown and bridge services remained higher in major city compared with other
      locations in 2003-2004. CONCLUSIONS: While the overall content of dentist
      workloads has changed to include less emphasis on removal and replacement of
      teeth and more effort on diagnosis and prevention aimed at retention of natural
      dentitions, a gap by location remains, with dentist workloads outside of major
      city locations marked by higher rates of tooth extraction and lower rates of
      preventive services.

PMID- 17542793
TI  - Australian rural adolescents' experiences of accessing psychological help for a
      mental health problem.
AB  - OBJECTIVE: This study aims to explore Australian rural adolescents' experiences
      of accessing help for a mental health problem in the context of their rural
      communities. DESIGN AND SETTING: A qualitative research design was used whereby
      university students who had sought help for a mental health problem during their
      adolescence were interviewed about their experiences. Interviews were conducted
      face-to-face at the university. MAIN OUTCOME MEASURES: A semi-structured
      interview schedule was designed around the study's main research questions. Audio
      taped interviews were transcribed and thematically coded using a constant
      comparative method. PARTICIPANTS: Participants were first-year undergraduate
      psychology students between the ages of 17 and 21 years who sought help for a
      mental health issue during their adolescence and who at that time resided in a
      rural area. RESULTS: Participants highlighted various barriers to seeking help
      for mental health problems in the context of a rural community, including: social
      visibility, lack of anonymity, a culture of self-reliance, and social stigma of
      mental illness. Participants' access to help was primarily school-based, and
      participants expressed a preference for supportive counselling over structured
      interventions. Characteristics of school-based helpers that made them
      approachable included: 'caring', 'nonjudgemental', 'genuine', 'young', and able
      to maintain confidentiality. CONCLUSIONS: The findings support previous research
      that reveals barriers to help seeking for mental health problems that are unique
      to the culture of rural communities. The study raises questions about the merit
      of delivery of primary mental health care to young people via GPs alone and
      suggests that school-based counsellors be considered as the first step in a young
      person's access to mental health care.

PMID- 17542794
TI  - Depression and remoteness from health services in South Australia.
AB  - OBJECTIVE: To determine whether the prevalence of depression, its associated
      quality of life, treatment and mental health literacy about depression varied
      according to accessibility to health services. DESIGN: Face-to-face interviews
      with a random and representative sample of the South Australian population (aged
      >or= 15 years) were conducted between March and June 2004, with the respondents
      stratified using the Accessibility and Remoteness Index of Australia into
      categories of 'highly accessible', 'accessible', and 'moderately accessible and
      remote'. RESULTS: From 4700 households selected, 3015 participants were
      interviewed (65.9% response rate). The prevalence of major depression and other
      depressions was not significantly different between each of the categories,
      although there was a trend for those from moderately accessible and remote areas
      to be less depressed overall. A significantly lower proportion of respondents
      from moderately accessible and remote locations reported that they had family or
      close friends who had suffered from symptoms consistent with depression, or that
      they had ever had treatment for those symptoms. However, there was no significant
      difference between the groups in those who had ever had or who were currently
      taking antidepressant medication. For those who were depressed, a significantly
      higher proportion from the accessible, and moderately accessible and remote
      regions had seen a community or district health service, social worker or other
      counsellor as compared with those from the highly accessible area. CONCLUSIONS:
      These findings indicate that depression is no more prevalent in less accessible
      regions of South Australia, and that when it is present, its treatment, in terms
      of antidepressants, which can be considered as a proxy marker for the overall
      management of depression, is similar to treatment in more accessible areas.

PMID- 17542795
TI  - Prevalence of depression among adults in Oyo State, Nigeria: a comparative study
      of rural and urban communities.
AB  - OBJECTIVE: This study was designed to assess the current prevalence of depression
      in Oyo State, Nigeria and the rural-urban variation in prevalence. SETTING: This
      is a two-phase community-based cross-sectional study. The urban areas selected
      for the study are the Ibadan North-West and Egbeda local government areas. The
      rural area selected was the Saki-East local government area. PARTICIPANTS: A
      total of 1105 participants were recruited into the study. Multistage sampling
      technique was used to obtain a representative sample of the participants from the
      communities in Oyo State. The study was conducted using an interviewer
      administered structured questionnaire, and the general health questionnaire (GHQ
      12) as a screening tool. The second phase of the interview was conducted only for
      those participants with a score of more than 3 using the GHQ 12. These
      participants were then clinically examined using the Structured Clinical
      Interview DSM IV for assessment of clinical depression. MAIN OUTCOME MEASURE:
      Prevalence of depression. RESULTS: A total of 721 (65.2%) were from urban
      communities, while 384 (34.8%) were from the rural community. The overall
      prevalence of depression was found to be 5.2%. Depression was more prevalent
      among women than men (5.7% vs 4.8%, chi(2) = 0.36 P = 0.55), and among
      adolescents (9.6%, P = 0.04). Furthermore, depression was more common in the
      rural areas than in the urban areas (7.3% vs 4.2%, chi(2) = 4.94 P = 0.02).
      CONCLUSION: Depression is more common in rural than urban areas in the Nigerian
      population. Mental health education for adolescents and secondary school students
      should be encouraged in rural communities.

PMID- 17542796
TI  - Rural Remote and Metropolitan Area 3: the forgotten RRMA.

PMID- 17542797
TI  - Clinical teaching model for nursing practice.

PMID- 17542798
TI  - A volunteer bushfire workforce: lessons in community mobilisation.

PMID- 17542799
TI  - PHC RIS website: your connection to rural health communities.

PMID- 17542800
TI  - NRF: the health of the rural health workforce.

PMID- 17542802
TI  - The trajectory of minor stroke recovery for men and their female spousal
      caregivers: literature review.
AB  - AIM: This paper is a report of a narrative review to examine the current state of
      knowledge regarding the impact of minor stroke on male patients and their female
      spousal caregivers' recovery trajectory and quality of life. BACKGROUND: Minor
      stroke survivors are often discharged early in the recovery process. The
      perception of the healthcare community that these patients and their female
      spousal caregivers will experience an uneventful recovery may lead to inadequate
      preparation for the postdischarge period. METHODS: A range of databases was
      searched to identify papers addressing 'minor stroke', 'transitions', 'quality of
      life', 'chronic disease', 'caregivers' and 'spouse caregivers', including AARP
      Ageline, AMED, CINAHL, Evidence Based Medicine Reviews, MEDLINE and PsychInfo.
      Papers published in English from 1990 to December 2006 were included. Thirty-four
      papers were in the final data set. RESULTS: Minor stroke survivors and their
      female spousal caregivers may experience major challenges in adaptations
      postdischarge. The trajectory of minor stroke recovery may necessitate a re
      evaluation of life plans, rethinking of priorities and integration of resulting
      disabilities into current and emerging life situations for both stroke survivors
      and their female spousal caregivers. In many cases these adaptations are
      compounded by transitions associated with the normal ageing process. CONCLUSION:
      While there is extensive literature on stroke recovery and the role of caregivers
      in general, there is little available describing the recovery of minor stroke
      survivors in relation to the normal ageing process. Further research is needed
      examining recovery from a transitional perspective, to support nurses and other
      health professionals discharge planning.

PMID- 17542803
TI  - Barriers to reducing the use of restraints in residential elder care facilities.
AB  - AIM: This paper is a report of a study to compare perspectives of staff in
      residential elder care facilities with those of residents and family members from
      the same facilities about barriers to reducing the use of physical, chemical and
      environmental restraints. BACKGROUND: There is growing research evidence of the
      potential risk of physical and emotional harm of restraining residents in
      residential elder care facilities. Despite the potential harms, restraints
      continue to be a common practice in facilities across Australia. Little research
      has been undertaken to explore the barriers to reducing the use of restraints.
      METHOD: Eighteen individual interviews were conducted with staff, general
      practitioners and a pharmacist and three focus groups were conducted with a total
      of 12 residents and 17 family members associated with three residential elder
      care facilities in Melbourne, Australia in 2004. FINDINGS: The three
      participating facilities were committed to reducing the use of restraints,
      although physical, chemical and environmental restraints were used in all three
      facilities. Barriers to reducing restraint use included fear of resident injury,
      staff and resource limitations, lack of education and information about
      alternatives to restraints, environmental constraints, policy and management
      issues, beliefs and expectations (of staff, family and residents), inadequate
      review practices and communication barriers. CONCLUSION: Further education and
      support for staff and family members in evidence-based practice in relation to
      resident care and restraint use is needed in at least some residential elder care
      facilities.

PMID- 17542804
TI  - In response to: Tourangeau A.E., Doran D.M., McGillis Hall L., O'Brien Pallas L.,
      Pringle D., Tu J.V. & Cranley L.A. (2007) Impact of hospital nursing care on 30
      day mortality for acute medical patients. Journal of Advanced Nursing 57(1), 32
      44.

PMID- 17542809
TI  - The organotellurium compound ammonium trichloro(dioxoethylene-0,0') tellurate
      enhances neuronal survival and improves functional outcome in an ischemic stroke
      model in mice.
AB  - Ammonium trichloro(dioxoethylene-0,0') tellurate (AS101) is a non-toxic
      organotellurium compound with pleiotropic activities. It was recently shown to
      induce production of the neurotrophic factor glial cell line-derived neurotrophic
      factor and to rescue neuronal-like PC-12 cells from neurotrophic factor
      deprivation-induced apoptosis. In this study, we show that AS101 improves
      functional outcome and reduces brain damage in a mouse model of focal ischemic
      stroke. Both pre-stroke and post-stroke intraperitoneal treatments with AS101
      reduced infarct size and edema and improved the neurological function of the
      animals. AS101 treatments reduced both apoptotic and inflammatory caspase
      activities, and also inhibited protein tyrosine nitration suggesting that AS101
      suppresses oxidative stress. Studies of cultured neurons showed that AS101
      confers protection against apoptosis induced by either glucose deprivation or the
      lipid peroxidation product 4-hydroxynonenal. Moreover, AS101 treatment reduced
      glutamate-induced intracellular calcium elevation, a major contributor to
      neuronal death in stroke. As AS101 has an excellent safety profile in humans, our
      pre-clinical data suggest a potential therapeutic benefit of AS101 in patients
      suffering from stroke and other neurodegenerative conditions.

PMID- 17542810
TI  - Selective re-routing of prion protein to proteasomes and alteration of its
      vesicular secretion prevent PrP(Sc) formation.
AB  - Conversion of the cellular prion protein (PrP(C)) into the abnormal scrapie
      isoform (PrP(Sc)) is the hallmark of prion diseases, which are fatal and
      transmissible neurodegenerative disorders. ER-retained anti-prion recombinant
      single-chain Fv fragments have been proved to be an effective tool for inhibition
      of PrP(C) trafficking to the cell surface and antagonize PrP(Sc) formation and
      infectivity. In the present study, we have generated the secreted version of 8H4
      intrabody (Sec-8H4) in order to compel PrP(C) outside the cells. The stable
      expression of the Sec-8H4 intrabodies induces proteasome degradation of
      endogenous prion protein but does not influence its glycosylation profile and
      maturation. Moreover, we found a dramatic diverting of PrP(C) traffic from its
      vesicular secretion and, most importantly, a total inhibition of PrP(Sc)
      accumulation in NGF-differentiated Sec-8H4 PC12 cells. These results confirm that
      perturbing the intracellular traffic of endogenous PrP(C) is an effective
      strategy to inhibit PrP(Sc) accumulation and provide convincing evidences for
      application of intracellular antibodies in prion diseases.

PMID- 17542811
TI  - Inhibition of amyloid beta-peptide production by blockage of beta-secretase
      cleavage site of amyloid precursor protein.
AB  - Amyloid beta-peptide (Abeta) is implicated as the major causative agent in
      Alzheimer's disease (AD). Abeta is produced by the processing of the amyloid
      precursor protein (APP) by BACE1 (beta-secretase) and gamma-secretase. Many
      inhibitors have been developed for the secretases. However, the inhibitors will
      interfere with the processing of not only APP but also of other secretase
      substrates. In this study, we describe the development of inhibitors that prevent
      production of Abeta by specific binding to the beta-cleavage site of APP. We used
      the hydropathic complementarity (HC) approach for the design of short peptide
      inhibitors. Some of the HC peptides were bound to the substrate peptide (Sub W)
      corresponding to the beta-cleavage site of APP and blocked its cleavage by
      recombinant human BACE1 (rhBACE1) in vitro. In addition, HC peptides specifically
      inhibited the cleavage of Sub W, and not affecting other BACE1 substrates.
      Chemical modification allowed an HC peptide (CIQIHF) to inhibit the processing of
      APP as well as the production of Abeta in the treated cells. Such novel APP
      specific inhibitors will provide opportunity for the development of drugs that
      can be used for the prevention and treatment of AD with minimal side effects.

PMID- 17542812
TI  - Acetylcholine synthesis by choline acetyltransferase of a peripheral type as
      demonstrated in adult rat dorsal root ganglion.
AB  - pChAT is a splice variant of a peripheral type encoded alternatively by the gene
      for choline acetyltransferase of the common type (cChAT), the enzyme responsible
      for acetylcholine synthesis. Immunohistochemistry using pChAT antiserum has
      successfully visualized many known peripheral cholinergic cells, whereas most
      cChAT antibodies failed to do so. As, however, accumulating evidence indicates
      that pChAT expression also occurs in various non-cholinergic neurons, we examined
      possible acetylcholine production by pChAT in rat dorsal root ganglion as a
      model. The present study indicated that the ganglion neurons possessed pChAT, but
      never cChAT, mRNA and protein. Our detailed analysis further showed that, despite
      low enzyme activities of both choline acetyltransferase and acetylcholinesterase,
      the level of acetylcholine in the ganglion was as high as to that in various
      brain regions receiving cholinergic innervation. By using immunoprecipitation
      methods, we here provide evidence that pChAT definitely has enzyme activity
      enough to supply physiological concentrations of acetylcholine in the ganglion.
      We propose that pChAT contributes both to acetylcholine neurotransmission in
      physiologically identified cholinergic cells and to functions yet unknown in non
      cholinergic neurons. Thus pChAT provides a new window on the role of neuronal
      acetylcholine.

PMID- 17542813
TI  - Adrenoleukodystrophy: subcellular localization and degradation of
      adrenoleukodystrophy protein (ALDP/ABCD1) with naturally occurring missense
      mutations.
AB  - Mutation in the X-chromosomal adrenoleukodystrophy gene (ALD; ABCD1) leads to X
      linked adrenoleukodystrophy (X-ALD), a severe neurodegenerative disorder. The
      encoded adrenoleukodystrophy protein (ALDP/ABCD1) is a half-size peroxisomal ATP
      binding cassette protein of 745 amino acids in humans. In this study, we chose
      nine arbitrary mutant human ALDP forms (R104C, G116R, Y174C, S342P, Q544R, S606P,
      S606L, R617H, and H667D) with naturally occurring missense mutations and examined
      the intracellular behavior. When expressed in X-ALD fibroblasts lacking ALDP, the
      expression level of mutant His-ALDPs (S606L, R617H, and H667D) was lower than
      that of wild type and other mutant ALDPs. Furthermore, mutant ALDP-green
      fluorescence proteins (S606L and H667D) stably expressed in CHO cells were not
      detected due to rapid degradation. Interestingly, the wild type ALDP co-expressed
      in these cells also disappeared. In the case of X-ALD fibroblasts from an ALD
      patient (R617H), the mutant ALDP was not detected in the cells, but appeared upon
      incubation with a proteasome inhibitor. When CHO cells expressing mutant ALDP
      green fluorescence protein (H667D) were cultured in the presence of a proteasome
      inhibitor, both the mutant and wild type ALDP reappeared. In addition, mutant His
      ALDP (Y174C), which has a mutation between transmembrane domain 2 and 3, did not
      exhibit peroxisomal localization by immunofluorescense study. These results
      suggest that mutant ALDPs, which have a mutation in the COOH-terminal half of
      ALDP, including S606L, R617H, and H667D, were degraded by proteasomes after
      dimerization. Further, the region between transmembrane domain 2 and 3 is
      important for the targeting of ALDP to the peroxisome.

PMID- 17542814
TI  - Skin-to-skin care with the father after cesarean birth and its effect on newborn
      crying and prefeeding behavior.
AB  - BACKGROUND: Previous reports have shown that skin-to-skin care immediately after
      vaginal birth is the optimal form of care for full-term, healthy infants. Even in
      cases when the mother is awake and using spinal analgesia, early skin-to-skin
      contact between her and her newborn directly after cesarean birth might be
      limited for practical and medical safety reasons. The aim of the present study
      was to compare the effects of skin-to-skin contact on crying and prefeeding
      behavior in healthy, full-term infants born by elective cesarean birth and cared
      for skin-to-skin with their fathers versus conventional care in a cot during the
      first 2 hours after birth. METHODS: Twenty-nine father-infant pairs participated
      in a randomized controlled trial, in which infants were randomized to be either
      skin-to-skin with their father or next to the father in a cot. Data were
      collected both by tape-recording crying time for the infants and by naturalistic
      observations of the infants' behavioral response, scored every 15 minutes based
      on the scoring criteria described in the Neonatal Behavioral Assessment Scale
      (NBAS). RESULTS: The primary finding was the positive impact the fathers' skin-to
      skin contact had on the infants' crying behavior. The analysis of the tape
      recordings of infant crying demonstrated that infants in the skin-to-skin group
      cried less than the infants in the cot group (p<0.001). The crying of infants in
      the skin-to-skin group decreased within 15 minutes of being placed skin-to-skin
      with the father. Analysis of the NBAS-based observation data showed that being
      cared for on the father's chest skin-to-skin also had an impact on infant
      wakefulness. These infants became drowsy within 60 minutes after birth, whereas
      infants cared for in a cot reached the same stage after 110 minutes. Rooting
      activity was more frequent in the cot group than in the skin-to-skin group
      (p<0.01), as were sucking activities (p<or=0.001) and overall duration of
      wakefulness (p<0.01). CONCLUSIONS: The infants in the skin-to-skin group were
      comforted, that is, they stopped crying, became calmer, and reached a drowsy
      state earlier than the infants in the cot group. The father can facilitate the
      development of the infant's prefeeding behavior in this important period of the
      newborn infant's life and should thus be regarded as the primary caregiver for
      the infant during the separation of mother and baby.

PMID- 17542815
TI  - Taiwan's high rate of cesarean births: impacts of national health insurance and
      fetal gender preference.
AB  - BACKGROUND: Taiwan has a high rate of cesarean section, approximately 33 percent
      in the past decade. This study investigates and discusses 2 possible factors that
      may encourage the practice, one of which is fetal gender difference and the other
      is Taiwan's recently implemented National Health Insurance (NHI). METHODS: A
      logistic regression model was used with the 1989 and 1996 National Maternal and
      Infant Health Survey and with the 2001 to 2003 NHI Research Databases. RESULTS:
      Using survey data, we found a statistically significant 0.3 percent gender
      difference in parental choice for cesarean section. However, no statistically
      significant difference was found in the rate of cesarean section before and after
      NHI implementation. CONCLUSIONS: Taiwan's high cesarean section rate is not
      directly related to financial incentives under NHI, indicating that adjusting
      policy to lower financial incentives from NHI would have only limited effect.
      Likewise, focusing effort on the small gender difference is unlikely to have much
      impact. Effective campaigns by health authorities might be conducted to educate
      the general population about risks associated with cesarean section and the
      benefits of vaginal birth to the child, mother, and society.

PMID- 17542816
TI  - Effect of delivery method and timing of breastfeeding initiation on breastfeeding
      outcomes in Taiwan.
AB  - BACKGROUND: Few studies have examined the independent effect of delivery method
      and timing of breastfeeding initiation on the prevalence of breastfeeding. The
      objectives of this study were to examine the effect of method of delivery and
      timing of breastfeeding initiation on the prevalence of breastfeeding at 1 and 3
      months after delivery using a national sample from Taiwan. METHODS: The study
      population of 2,064 women who gave birth to infants without congenital anomalies
      at hospitals in Taiwan from June through October 2003, inclusively, participated
      in a postal questionnaire survey. RESULTS: Multivariate ordinal logistic
      regression analysis showed that women with cesarean delivery had a lower odds of
      breastfeeding at 1 and 3 months after delivery. Women with assisted vaginal
      delivery had lower odds of breastfeeding at 3 months after delivery compared with
      women with unassisted vaginal delivery. Initiation of breastfeeding within 30
      minutes of delivery was associated with higher odds of breastfeeding at 1 and 3
      months after delivery. Women who did not initiate breastfeeding during hospital
      stay but breastfed at 1 month after delivery had lower odds of breastfeeding at 3
      months after delivery. CONCLUSIONS: The findings suggest the importance of
      conservative use of operative obstetrical intervention due to its negative impact
      on breastfeeding. Health professionals need to support mothers who have
      experienced cesarean and assisted vaginal delivery to increase their
      breastfeeding. Hospital staff should improve practice with respect to early
      initiation of breastfeeding.

PMID- 17542817
TI  - Preparation for discharge, maternal satisfaction, and newborn readmission for
      jaundice: comparing postpartum models of care.
AB  - BACKGROUND: Physiological jaundice generally appears between the third and fifth
      days of life. The danger of hyperbilirubinemia is therefore a major challenge
      when postpartum hospital stays are short, and part of the responsibility for
      screening for signs of jaundice is assumed by the mother. The objective of this
      study was to identify the model of postnatal continuity of care most likely to
      prepare mothers for discharge, to reduce newborn readmission for jaundice, and to
      enhance maternal satisfaction. METHODS: An epidemiological study was conducted in
      regions operating under 3 different models of postnatal continuity of care.
      Eligible mothers were those who had spent less than 60 hours in hospital after an
      uncomplicated vaginal delivery. Of this group, 70.8 percent participated in
      telephone interviews conducted 1 month after their deliveries (n=1,096). Newborns
      who had presented with signs of jaundice were identified through statements from
      their mothers. RESULTS: Of the participating newborns, 45.5 percent presented
      with signs of jaundice, and 3.2 percent were readmitted for jaundice during the
      first week of life. The follow-up procedures used in regions operating under a
      community-based model most closely followed the recommendations of health
      authorities and featured a high level of mothers' satisfaction. In the region
      operating under a mixed hospital model, mothers reported signs of jaundice
      significantly more often, and postdischarge services received by mothers were
      less effective at allaying their fears compared with other models. Phototherapy
      was offered in the home only in the region operating under a mixed ambulatory
      model, and no readmissions for jaundice were recorded in this region.
      CONCLUSIONS: An effective coordination between community-based perinatal services
      and hospital-linked home phototherapy in the form of an integrated network
      appears to be an essential condition for improved monitoring of newborns' health
      since it fosters a follow-up that is focused not only on jaundice but also on
      mothers' and newborns' needs while reducing the costs generated by newborn
      readmissions.

PMID- 17542818
TI  - Outcomes of planned hospital birth attended by midwives compared with physicians
      in British Columbia.
AB  - BACKGROUND: The impact of midwifery versus physician care on perinatal outcomes
      in a population of women planning birth in hospital has not yet been explored. We
      compared maternal and newborn outcomes between women planning hospital birth
      attended by a midwife versus a physician in British Columbia, Canada. METHODS:
      All women planning a hospital birth attended by a midwife during the 2-year study
      period who were of sufficiently low-risk status to meet eligibility requirements
      for home birth as defined by the British Columbia College of Midwives were
      included in the study group (n=488). The comparison group included women meeting
      the same eligibility requirements but planning a physician-attended birth in
      hospitals where midwives also practiced (n=572). Outcomes were ascertained from
      the British Columbia Reproductive Care Program Perinatal Registry to which all
      hospitals in the province submit data. RESULTS: Adjusted odds ratios for women
      planning hospital birth attended by a midwife versus a physician were
      significantly reduced for exposure to cesarean section (OR 0.58, 95% CI 0.39
      0.86), narcotic analgesia (OR 0.26, 95% CI 0.18-0.37), electronic fetal
      monitoring (OR 0.22, 95% CI 0.16-0.30), amniotomy (OR 0.74, 95% CI 0.56-0.98),
      and episiotomy (OR 0.62, 95% CI 0.42-0.93). The odds of adverse neonatal outcomes
      were not different between groups, with the exception of reduced use of drugs for
      resuscitation at birth (OR 0.19, 95% CI 0.04-0.83) in the midwifery group.
      CONCLUSIONS: A shift toward greater proportions of midwife-attended births in
      hospitals could result in reduced rates of obstetric interventions, with similar
      rates of neonatal morbidity.

PMID- 17542819
TI  - Satisfaction with cesarean section: qualitative analysis of open-ended questions
      in a large postal survey.
AB  - BACKGROUND: Cesarean section rates throughout the developed world continue to
      rise. Although satisfaction with cesarean section has been widely studied,
      relatively little is known about the causes of "distress" that may contribute to
      dissatisfaction. The aim of this study was to explore the factors that women
      identified as "distressing" so as to understand their responses to standard
      questions on satisfaction. METHODS: A questionnaire study of 1,661 women who had
      delivered their first babies by cesarean section in Aberdeen, Scotland, between
      1980 and 1995 elicited a 75 percent response rate and showed that 81 percent of
      women were satisfied with the experience. Nevertheless, 36 percent rated an
      aspect as distressing, and 42 percent provided written descriptions of one or
      more experiences that had distressed them. These responses were coded using
      content analysis into 5 major categories: before, during, and after the birth,
      psychological/general, and overall. RESULTS: The most distressing factors were of
      a psychological or general nature, with 66 percent of distressed women mentioning
      poor communications, fears, missing out on the birth or the immediate postpartum
      period, or other emotions. Events happening before, during, and after the birth
      caused 23, 45, and 44 percent of women to be distressed, respectively. Surgical
      complications and infections were distressing, but anesthesia was the single
      factor that caused most distress, leaving 102 women (20%) with unsatisfactory
      memories of the birth. CONCLUSIONS: The impact of cesarean birth on women's
      psychological well-being is highlighted by this study. Enhanced communication
      during labor and delivery, and preparation or education on issues surrounding
      cesarean section, can reduce distress and improve women's satisfaction with
      birth.

PMID- 17542820
TI  - Women's views and outcomes of an educational intervention designed to enhance
      psychosocial support for women during pregnancy.
AB  - BACKGROUND: Identification of psychosocial issues in pregnant women by screening
      is difficult because of the lack of accuracy of screening tools, women's
      reluctance to disclose sensitive issues, and health care practitioner's
      reluctance to ask. This paper evaluates if a health professional education
      program, a new (ANEW) approach, improves pregnant women's ratings of care and
      practitioner's listening skills and comfort to disclose psychosocial issues.
      METHODS: Midwives and doctors from Mercy Hospital for Women, Melbourne,
      Australia, were trained from August to December 2002. English-speaking women (<20
      wks' gestation) were recruited at their first visit and mailed a survey at 30
      weeks (early 2002) before and after (2003) the ANEW educational intervention.
      Follow-up was by postal reminder at 2 weeks and telephone reminder 2 weeks later.
      RESULTS: Twenty-one midwives and 5 doctors were trained. Of the eligible women,
      78.2 percent (584/747) participated in a pre-ANEW survey and 73.3 percent
      (481/657) in a post-ANEW survey. After ANEW, women were more likely to report
      that midwives asked questions that helped them to talk about psychosocial
      problems (OR 1.45, CI 1.09-1.98) and that they would feel comfortable to discuss
      a range of psychosocial issues if they were experiencing them (coping after birth
      for midwives [OR 1.51, CI 1.10-2.08] and feeling depressed [OR 1.49, 1.16-1.93];
      and concerns relating to sex [OR 1.35, CI 1.03-1.77] or their relationships [OR
      1.36, CI 1.00-1.85] for doctors). CONCLUSIONS: The ANEW program evaluation
      suggests trends of better communication by health professionals for pregnant
      women and should be evaluated using rigorous methods in other settings.

PMID- 17542821
TI  - Evaluating maternity care: a core set of outcome measures.
AB  - BACKGROUND: Comparing the relative effectiveness of interventions on specific
      outcomes across trials can be problematic due to differences in the choice and
      definitions of outcome measures used by researchers. We sought to identify a
      minimum set of outcome measures for evaluating models of maternity care from the
      perspective of key stakeholders. METHODS: A 3-round, electronic Delphi survey
      design was used. Setting was multinational, comprising a range of key
      stakeholders. Participants consisted of a single heterogeneous panel of maternity
      service users, midwives, obstetricians, pediatricians/neonatologists, family
      physicians/general practitioners, policy-makers, service practitioners, and
      researchers of maternity care. Members of the panel self-assessed their expertise
      in evaluating models of maternity care. RESULTS: A total of 320 people from 28
      countries expressed willingness to take part in this survey. Round 1 was
      completed by 218 (68.1%) participants, of whom 173 (79.4%) completed round 2 and
      152 (87.9%) of these completed round 3. Fifty outcomes were identified, with both
      a mean value greater than the overall group mean for all outcomes combined
      (x=4.18) and rated 4 or more on a 5-point Likert-type scale for importance of
      inclusion in a minimum data set of outcome measures by at least 70 percent of
      respondents. Three outcomes were collapsed into a single outcome so that the
      final minimum set includes 48 outcomes. CONCLUSIONS: Given the inconsistencies in
      the choice of outcome measures routinely collected and reported in randomized
      evaluations of maternity care, it is hoped that use of the data set will increase
      the potential for national and international comparisons of models for maternity
      care. Although not intended to be prescriptive or to inhibit the collection of
      other outcomes, we hope that the core set will make it easier to assess the care
      of women and their babies during pregnancy and childbirth.

PMID- 17542822
TI  - Compressive neuropathies complicating normal childbirth: case report and
      literature review.
AB  - BACKGROUND: Peroneal neuropathy has been well described in the literature, but
      few cases have been reported of bilateral peroneal neuropathy as a complication
      of normal childbirth. Most reported cases are due to prolonged squatting during
      childbirth, which is prevalent in certain countries. CASE REPORT: A 30-year-old
      woman developed bilateral footdrop shortly after normal vaginal delivery under
      epidural analgesics. Neurological examination and electrodiagnostic studies
      confirmed bilateral common peroneal mononeuropathy most likely secondary to
      prolonged and excessive pressure around the knees by attendants who were
      assisting at the delivery. The woman showed significant improvement of her
      symptoms after physical therapy and assisted devices. CONCLUSIONS: Excessive and
      prolonged pressure knee holding during normal childbirth may result in
      compressive peripheral neuropathy. Patient education and awareness among the
      labor and delivery team will prevent this avoidable complication.

PMID- 17542823
TI  - In the literature: combating coercion: breech birth, parturient choice, and the
      evolution of evidence-based maternity care.

PMID- 17542827
TI  - Effectiveness of postpartum support.

PMID- 17542830
TI  - Identification of contaminant sources in enclosed environments by inverse CFD
      modeling.
AB  - In case contaminants are found in enclosed environments such as aircraft cabins
      or buildings, it is useful to find the contaminant sources. One method to locate
      contaminant sources is by inverse computational fluid dynamics (CFD) modeling. As
      the inverse CFD modeling is ill posed, this paper has proposed to solve a quasi
      reversibility (QR) equation for contaminant transport. The equation improves the
      numerical stability by replacing the second-order diffusion term with a fourth
      order stabilization term in the governing equation of contaminant transport. In
      addition, a numerical scheme for solving the QR equation in unstructured meshes
      has been developed. This paper demonstrates how to use the inverse CFD model with
      the QR equation and numerical scheme to identify gaseous contaminant sources in a
      two-dimensional aircraft cabin and in a three-dimensional office. The inverse CFD
      model could identify the contaminant source locations but not very accurate
      contaminant source strength because of the dispersive property of the QR
      equation. The results also show that this method works better for convection
      dominant flows than the flows that convection is not so important. PRACTICAL
      IMPLICATIONS: This paper presents a methodology that can be used to find
      contaminant source locations and strengths in enclosed environments with the data
      of airflow and contaminants measured by sensors. The method can be a very useful
      tool to find where, what, and how contamination has happened. The results can be
      used to develop appropriate measures to protect occupants in the enclosed
      environments from infectious diseases or terrorist releases of
      chemical/biological warfare agents as well as to decontaminate the environments.

PMID- 17542831
TI  - 3D-CFD analysis of diffusion and emission of VOCs in a FLEC cavity.
AB  - This study is performed as a part of research that examines the emission and
      diffusion characteristics of volatile organic compounds (VOCs) from indoor
      building materials. In this paper, the flow field and the emission field of VOCs
      from the surface of building materials in a Field and Laboratory Emission Cell
      (FLEC) cavity are examined by 3D Computational Fluid Dynamics (CFD) analysis. The
      flow field within the FLEC cavity is laminar. With a total flow of 250 ml/min,
      the air velocity near the test material surface ranges from 0.1 to 4.5 cm/s.
      Three types of emission from building materials are studied here: (i) emission
      phenomena controlled by internal diffusion, (ii) emission phenomena controlled by
      external diffusion, and (iii) emission phenomena controlled by mixed diffusion
      (internal + external diffusion). In the case of internal diffusion material, with
      respect to the concentration distribution in the cavity, the local VOC emission
      rate becomes uniform and the FLEC works well. However, in the case of evaporation
      type (external diffusion) material, or mixed type materials (internal + external
      diffusion) when the resistance to transporting VOCs in the material is small, the
      FLEC is not suitable for emission testing because of the thin FLEC cavity. In
      this case, the mean emission rate is restricted to a small value, since the VOC
      concentration in the cavity rises to the same value as the surface concentration
      through molecular diffusion within the thin cavity, and the concentration
      gradient normal to the surface becomes small. The diffusion field and emission
      rate depend on the cavity concentration and on the Loading Factor. That is, when
      the testing material surface in the cavity is partially sealed to decrease the
      Loading Factor, the emission rate become higher with the decrease in the exposed
      area of the testing material. PRACTICAL IMPLICATIONS: The flow field and
      diffusion field within the FLEC cavity are investigated by CFD method. After
      presenting a summary of the velocity distributed over the surface of test
      material and the emission properties of different type materials in FLEC, the
      paper pointed out that there is a bias in the airflow inside the FLEC cavity but
      do not influence the result of test emission rate, and the FLEC method is
      unsuitable for evaporation type materials in which the mass transfer of the
      surface controls the emission rate.

PMID- 17542832
TI  - Household CO and PM measured as part of a review of China's National Improved
      Stove Program.
AB  - In 2001-2003, a team of researchers from the United States and China performed an
      independent, multidisciplinary review of China's National Improved Stove Program
      carried out since the 1980s. As part of a 3500-household survey, a subsample of
      396 rural households were monitored for particulate matter less than 4 microm
      (PM(4)) in kitchens and living rooms over 24 h, of which 159 were measured in
      both summer and winter. Carbon monoxide was measured in a 40% subsample. The
      results of this indoor air quality (IAQ) component indicate that for nearly all
      household stove or fuel groupings, PM(4) levels were higher than - and sometimes
      more than twice as high as - the national PM(10) standard for indoor air (150
      microg PM(10)/m(3)). If these results are typical, then a large fraction of
      China's rural population is now chronically exposed to levels of pollution far
      higher than those determined by the Chinese government to harm human health.
      Further, we observed highly diverse fuel usage patterns in these regions in
      China, supporting the observations in the household survey of multiple stoves
      being present in many kitchens. Improved stoves resulted in reduced PM(4) from
      biomass fuel combinations, but still not at levels that meet standards, and
      little improvement was observed in indoor pollution levels when other unimproved
      stoves were present in the same kitchen. As many households change fuels
      according to daily and seasonal factors, resulting in different seasonal
      concentrations in living rooms and kitchens, assessing health implications from
      fuel use requires longitudinal evaluation of fuel use and IAQ levels, combined
      with accurate time-activity information. PRACTICAL IMPLICATIONS: Leaving aside
      the difficult issue of enforcement, it is uncertain whether Chinese household IAQ
      standards represent realistic objectives for current attainment given current
      patterns of energy consumption in rural China, which rely so heavily on
      unprocessed solid fuels. Even when used with chimneys, these fuels emit
      substantial pollution into the household environment. It is probable that low
      emission technologies involving gaseous/liquid fuels or high combustion -
      efficiency biomass stoves need to be promoted in order to achieve these standards
      for the greater part of the population.

PMID- 17542833
TI  - Perception of cabin air quality in airline crew related to air humidification, on
      intercontinental flights.
AB  - The influence of air humidification in aircraft, on perception of cabin air
      quality among airline crew (N = 71) was investigated. In-flight investigations
      were performed in the forward part and in the aft part on eight intercontinental
      flights with one Boeing 767 individually, equipped with an evaporation humidifier
      combined with a dehumidifying unit, to reduce accumulation of condensed water in
      the wall construction. Four flights had the air humidification active when going
      out, and turned off on the return flight. The four others had the inverse
      humidification sequence. The sequences were randomized, and double blind. Air
      humidification increased relative air humidity (RH) by 10% in forward part, and
      by 3% in aft part of the cabin and in the cockpit. When the humidification device
      was active, the cabin air was perceived as being less dry (P = 0.008), and
      fresher (P = 0.002). The mean concentration of viable bacteria (77-108 cfu/m(3)),
      viable molds (74-84 cfu/m(3)), and respirable particles (1-8 microg/m3) was low,
      both during humidified and non-humidified flights. On flights with air
      humidification, there were less particles in the forward part of the aircraft (P
      = 0.01). In conclusion, RH can be slightly increased by using ceramic evaporation
      humidifier, without any measurable increase of microorganisms in cabin air. The
      cabin air quality was perceived as being better with air humidification.
      PRACTICAL IMPLICATION: Relative air humidity is low (10-20%) during
      intercontinental flights, and can be increased by using ceramic evaporation
      humidifier, without any measurable increase of microorganism in cabin air. Air
      humidification could increase the sensation of better cabin air quality.

PMID- 17542834
TI  - How far droplets can move in indoor environments--revisiting the Wells
      evaporation-falling curve.
AB  - A large number of infectious diseases are believed to be transmitted between
      people via large droplets and by airborne routes. An understanding of evaporation
      and dispersion of droplets and droplet nuclei is not only significant for
      developing effective engineering control methods for infectious diseases but also
      for exploring the basic transmission mechanisms of the infectious diseases. How
      far droplets can move is related to how far droplet-borne diseases can transmit.
      A simple physical model is developed and used here to investigate the evaporation
      and movement of droplets expelled during respiratory activities; in particular,
      the well-known Wells evaporation-falling curve of droplets is revisited
      considering the effect of relative humidity, air speed, and respiratory jets. Our
      simple model considers the movement of exhaled air, as well as the evaporation
      and movement of a single droplet. Exhaled air is treated as a steady-state non
      isothermal (warm) jet horizontally issuing into stagnant surrounding air. A
      droplet is assumed to evaporate and move in this non-isothermal jet. Calculations
      are performed for both pure water droplets and droplets of sodium chloride
      (physiological saline) solution (0.9% w/v). We calculate the droplet lifetimes
      and how droplet size changes, as well as how far the droplets travel in different
      relative humidities. Our results indicate that a droplet's size predominately
      dictates its evaporation and movement after being expelled. The sizes of the
      largest droplets that would totally evaporate before falling 2 m away are
      determined under different conditions. The maximum horizontal distances that
      droplets can reach during different respiratory activities are also obtained. Our
      study is useful for developing effective prevention measures for controlling
      infectious diseases in hospitals and in the community at large. PRACTICAL
      IMPLICATIONS: Our study reveals that for respiratory exhalation flows, the sizes
      of the largest droplets that would totally evaporate before falling 2 m away are
      between 60 and 100 microm, and these expelled large droplets are carried more
      than 6 m away by exhaled air at a velocity of 50 m/s (sneezing), more than 2 m
      away at a velocity of 10 m/s (coughing) and less than 1 m away at a velocity of 1
      m/s (breathing). These findings are useful for developing effective engineering
      control methods for infectious diseases, and also for exploring the basic
      transmission mechanisms of the infectious diseases. There is a need to examine
      the air distribution systems in hospital wards for controlling both airborne and
      droplet-borne transmitted diseases.

PMID- 17542835
TI  - Public health and economic impact of dampness and mold.
AB  - The public health risk and economic impact of dampness and mold exposures was
      assessed using current asthma as a health endpoint. Individual risk of current
      asthma from exposure to dampness and mold in homes from W.J. Fisk, Q. Lei-Gomez &
      M.J. Mendell [(2007) Indoor Air, [corrected] 17, 284-296], and [corrected] asthma
      risks calculated from additional studies that reported the prevalence of dampness
      and mold in homes were used to estimate the proportion of US current asthma cases
      that are attributable to dampness and mold exposure at 21% (95% confidence
      internal 12-29%). An examination of the literature covering dampness and mold in
      schools, offices, and institutional buildings, which is summarized in the
      Appendix, suggests that risks from exposure in these buildings are similar to
      risks from exposures in homes. Of the 21.8 million people reported to have asthma
      in the USA, approximately 4.6 (2.7-6.3) million cases are estimated to be
      attributable to dampness and mold exposure in the home. Estimates of the national
      cost of asthma from two prior studies were updated to 2004 and used to estimate
      the economic impact of dampness and mold exposures. By applying the attributable
      fraction to the updated national annual cost of asthma, the national annual cost
      of asthma that is attributable to dampness and mold exposure in the home is
      estimated to be $3.5 billion ($2.1-4.8 billion). Analysis indicates that exposure
      to dampness and mold in buildings poses significant public health and economic
      risks in the USA. These findings are compatible with public policies and programs
      that help control moisture and mold in buildings. PRACTICAL IMPLICATIONS: There
      is a need to control moisture in both new and existing construction because of
      the significant health consequences that can result from dampness and mold. This
      paper demonstrates that dampness and mold in buildings is a significant public
      health problem with substantial economic impact.

PMID- 17542836
TI  - Do indoor chemicals promote development of airway allergy?
AB  - Allergic asthma has increased worldwide in the industrialized countries. This
      review evaluates whether the major groups of indoor chemical exposures possess
      allergy-promoting (adjuvant) effects; formaldehyde was excluded, because of the
      size of the literature. Volatile organic compounds (VOCs) are used as an example
      of gases and vapors. The precipitation of asthmatic symptoms by VOC exposures is
      probably because of VOC levels considerably above typical indoor levels, or VOCs
      may be a surrogate for exposure to allergens, combustion products or dampness.
      Indoor particles possessed adjuvant effects in animal studies and allergy
      promoting effects in humans. Quaternary ammonium compounds may possess adjuvant
      effects in animal studies and promoted sensitization in humans in occupational
      settings. The use of cleaning agents, anionic and non-ionic surfactants are not
      considered to possess an important adjuvant effect in the general population.
      Regarding phthalate exposures, results from animal and epidemiological studies
      were found to be discordant. There is little evidence that the indoor chemicals
      evaluated possess important adjuvant effects. If buildings are kept clean, dry
      and free of combustion products, the important question may be would it be
      profitable to look for lifestyle factors and non-chemical indoor exposures in
      order to abate airway allergy? PRACTICAL IMPLICATIONS: Indoor chemicals
      (pollutants) have been accused to promote development of airway allergy by
      adjuvant effects. In this review, we evaluated the scientific literature and
      found little support for the supposition that indoor chemicals possess important
      adjuvant effects. This rises the question: would it be profitable for abatement
      of airway allergy to look for non-chemical indoor exposures, including lifestyle
      factors, and exposures to allergens, microorganisms, including vira, and their
      interactions?

PMID- 17542837
TI  - Making evolution relevant and exciting to biology students.

PMID- 17542838
TI  - Hamilton's forces of natural selection after forty years.
AB  - In 1966, William D. Hamilton published a landmark paper in evolutionary biology:
      "The Moulding of Senescence by Natural Selection." It is now apparent that this
      article is as important as his better-known 1964 articles on kin selection. Not
      only did the 1966 article explain aging, it also supplied the basic scaling
      forces for natural selection over the entire life history. Like the Lorentz
      transformations of relativistic physics, Hamilton's Forces of Natural Selection
      provide an overarching framework for understanding the power of natural selection
      at early ages, the existence of aging, the timing of aging, the cessation of
      aging, and the timing of the cessation of aging. His twin Forces show that
      natural selection shapes survival and fecundity in different ways, so their
      evolution can be somewhat distinct. Hamilton's Forces also define the context in
      which genetic variation is shaped. The Forces of Natural Selection are readily
      manipulable using experimental evolution, allowing the deceleration or
      acceleration of aging, and the shifting of the transition ages between
      development, aging, and late life. For these reasons, evolutionary research on
      the demographic features of life history should be referred to as "Hamiltonian."

PMID- 17542839
TI  - Kin selection and evolution of infectious disease resistance.
AB  - Discoveries of mutations conferring resistance to infectious diseases have led to
      increased interest in the evolutionary dynamics of disease resistance. Several
      recent papers have estimated the historical strength of selection for mutations
      conferring disease resistance. These studies are based on simple population
      genetic models that do not take account of factors such as spatial and family
      structure. Such factors may have a substantial impact on the strength of natural
      selection through inclusive fitness effects. That is, people have a strong
      tendency to live with relatives and therefore have a high probability of
      transmitting infectious diseases to them. Thus, an allele that protects an
      individual against disease infection also protects that individual's family
      members. Because some of these family members are likely to also be carrying the
      allele, selection for that allele is magnified by family structure. In this
      paper, I use mathematical modeling techniques to explore the impact of such kin
      selection on the strength of selection for infectious disease resistance alleles.
      I show that if the resistance allele has the same proportional effect on both
      within- and between-family transmission, then the impact of kin selection is
      relatively minor. Selection coefficients are increased by 5-35%, with a greater
      benefit for weaker alleles. The reason is that an individual with a strong
      resistance allele does not need much protection from infection by family members
      and thus does not benefit much from their alleles. The effect of kin selection
      can be dramatic, however, if the resistance allele has a larger effect on between
      family transmission than within-family transmission (which can occur if between
      family infection rates are much smaller than within-family rates), increasing
      selection coefficients by as much as two- to threefold. These results show
      conditions when it is important to consider family structure in estimates of the
      strength of selection for infectious disease resistance alleles.

PMID- 17542840
TI  - Effects of kin-structured seed dispersal on the genetic structure of the clonal
      dioecious shrub ilex leucoclada.
AB  - Nonrandom patterns of gene dispersal have been identified as possible causes of
      genetic structuring within populations. Attempts to model these patterns have
      generally focused solely on the effects of isolation by distance, but the
      processes involved are more complex than such modeling suggests. Here, we extend
      considerations of gene dispersal processes beyond simple isolation by distance
      effects by directly evaluating the effects of kin-structured gene dispersal
      mediated by the group dispersal of related seeds within fruits (i.e., kin
      structured seed dispersal) by birds on genetic structure in Ilex leucoclada, a
      clonal dioecious shrub. To examine the genetic structure patterns, we established
      two 30x30 m plots (one with immature soils in old-growth forest and one in
      secondary forest, designated IM and SC, respectively) with different I.
      leucoclada stem densities. In these two plots 145 and 510 stems were found,
      representing 78 and 85 genets, respectively, identified by analyzing their
      genotypes at eight microsatellite loci. The clonal structure was stronger in the
      SC plot than in the IM plot. Correlograms of coancestry for genets in both plots
      exhibited significant, positive, high values in the shortest distance class,
      indicating the presence of strong genetic structure. However, Sp statistics
      revealed that the pattern of the genetic structure differed between the plots. In
      addition, to estimate the family structure within fruits, we sampled forty
      fruits, in total, from 15 randomly selected plants in the area around the IM and
      SC plots, and found that 80% of the fruits were multiseeded and 42-100% of the
      multiseeded fruits contained at least one pair of full sibs. Simulations based on
      these estimates demonstrated that the group dispersal of related seeds produced
      through correlated mating both within and across fruits, but not unstructured
      half-sib dispersal, could generate the observed magnitude and trends of genetic
      structure found in the IM plot. Furthermore, in addition to kin-structured seed
      dispersal, isolation by distance processes is also likely to promote genetic
      substructuring in the SC plot. After discussing possible ecological factors that
      may have contributed to the observed genetic structure, we contrast our results
      with those predicted by general isolation by distance models, and propose that
      kin-structured seed dispersal should promote some evolutionary phenomena, and
      thus should be incorporated, where appropriate, in models of gene dispersal in
      natural plant populations.

PMID- 17542841
TI  - Repeated evolution of male sacrifice behavior in spiders correlated with genital
      mutilation.
AB  - According to sexual cannibalism theory, male complicity in terminal mating can be
      adaptive when the male's future reproductive value is low relative to the
      benefits of self sacrifice. Spiders and insects that exhibit male sacrifice
      behavior (either complicity in cannibalism or spontaneous death associated with
      copulation) often also have male genitalia that stereotypically become broken or
      disfigured the first time they are used for copulation, potentially lowering his
      future reproductive value. Theoretical work on monogamy has identified male bias
      in the effective sex ratio as a precursor to the evolution of monogamy (including
      male sacrifice) as an adaptive form of paternity protection. Using phylogeny
      based statistics and drawing on several phylogenetic studies of araneoid spiders,
      I investigate relationships between male sacrifice behavior, genital mutilation,
      extreme sexual size dimorphism, and the accumulation of multiple males in the
      female web (as an indicator of a male-based effective sex ratio). This
      investigation focuses on araneoid spiders because several independent origins of
      sacrifice behavior are known for this group and the phylogenetic structure of the
      lineage is relatively well studied. I report that male genital mutilation is
      significantly correlated with sacrifice behavior and argue that this finding is
      consistent with sexual cannibalism theory. Male sacrifice behavior is also
      correlated with male accumulation, a result that is consistent with theoretical
      work on the evolution of monogamy. Male accumulation and extreme sexual size
      dimorphism are correlated suggesting that sex-based differences in maturation
      time can lead to a male biased effective sex ratio. Similar patterns of
      correlated characters may hold for some insect taxa. Studying traits that have
      appeared independently in multiple lineages is a powerful method for developing
      general theories about the evolution of biological phenomena.

PMID- 17542842
TI  - The intensity of sexual selection predicts weapon size in male bovids.
AB  - As a classical example of a sexually selected trait, the horns of male bovids
      offer a prime opportunity to identify predictors of the intensity of sexual
      selection. Here I use the comparative method to quantify sexual and natural
      selection pressures behind interspecific variation in horn length. I show that
      male horn length depends on factors proposed to affect the mean mate number per
      mating male, correlating positively with group size and negatively with male
      territoriality. This suggests that whereas group size increases the opportunity
      for sexual selection, territoriality reduces it because territorial males are
      unable to follow and monopolize female groups as effectively as males in
      nonterritorial species. Sexual body size dimorphism also correlates positively
      with group size and negatively with territoriality, corroborating these factors
      as predictors of the intensity of sexual selection on males. Female horn length
      was unaffected by the factors related to mating system, suggesting that this
      trait is mainly under natural selection. Using female horn length as a proxy for
      forces of natural selection revealed a negative effect on male horn length. Thus
      where natural selection favors female horns, possibly as effective weapons
      against predators, a similar selection pressure on males might prevent them from
      evolving too elaborate horns through sexual selection. There was no correlation
      found between horn length and latitude, thus providing no support for the
      hypothesis that horns have a thermoregulatory function.

PMID- 17542843
TI  - Heterospecific aggression and adaptive divergence in brook stickleback (Culaea
      inconstans).
AB  - Agonistic behavior between heterospecifics, in which individuals of one species
      attack another, may cause a subordinate species to shift resource or habitat use.
      Subsequent evolutionary responses to selection may mimic shifts expected under
      ecological character displacement, but with no role played by exploitative
      competition. Alternatively, aggressive behavior can evolve when fitness is
      improved by excluding members of a coexisting species from a defendable resource
      through interference. We tested whether heterospecific agonistic behavior has
      evolved in brook stickleback (Culaea inconstans) by comparing replicate
      allopatric populations to those sympatric with ninespine stickleback (Pungitius
      pungitius). We also tested for heritable variation in heterospecific aggressive
      behavior by rearing family groups in a common environment. Allopatric populations
      of brook stickleback were more aggressive than ninespine stickleback, suggesting
      that pre-existing aggression in brook stickleback contributed to niche shifts by
      ninespine stickleback. In addition, sympatric adult brook stickleback were more
      aggressive toward ninespine stickleback than brook stickleback from allopatric
      populations. Overt heterospecific aggressive behaviors were heritable, and
      aggression in juvenile brook stickleback increased with age in sympatric but not
      in allopatric populations reared in a common environment. Brook stickleback have
      evolved increased aggression when they coexist with ninespine stickleback. These
      stickleback communities have been structured by both evolved and pre-existing
      variation in heterospecific aggressive behavior in brook stickleback.

PMID- 17542844
TI  - Inbreeding and outbreeding depression in Caenorhabditis nematodes.
AB  - The nematode Caenorhabditis elegans reproduces primarily by self-fertilization of
      hermaphrodites, yet males are present at low frequencies in natural populations
      (androdioecy). The ancestral state of C. elegans was probably gonochorism
      (separate males and females), as in its relative C. remanei. Males may be
      maintained in C. elegans because outcrossed individuals escape inbreeding
      depression. The level of inbreeding depression is, however, expected to be low in
      such a highly selfing species, compared with an outcrosser like C. remanei. To
      investigate these issues, we measured life-history traits in the progeny of
      inbred versus outcrossed C. elegans and C. remanei individuals derived from
      recently isolated natural populations. In addition, we maintained inbred lines of
      C. remanei through 13 generations of full-sibling mating. Highly inbred C.
      remanei showed dramatic reductions in brood size and relative fitness compared to
      outcrossed individuals, with evidence of both direct genetic and maternal-effect
      inbreeding depression. This decline in fitness accumulated over time, causing
      extinction of nearly 90% of inbred lines, with no evidence of purging of
      deleterious mutations from the remaining lines. In contrast, pure strains of C.
      elegans performed better than crosses between strains, indicating outbreeding
      depression. The results are discussed in relation to the evolution of androdioecy
      and the effect of mating system on the level of inbreeding depression.

PMID- 17542845
TI  - Genetic evidence from mitochondrial, nuclear, and endosymbiont markers for the
      evolution of host plant associated species in the aphid genus Hyalopterus
      (Hemiptera: Aphididae).
AB  - Over the past several decades biologists' fascination with plant-herbivore
      interactions has generated intensive research into the implications of these
      interactions for insect diversification. The study of closely related
      phytophagous insect species or populations from an evolutionary perspective can
      help illuminate ecological and selective forces that drive these interactions.
      Here we present such an analysis for aphids in the genus Hyalopterus (Hemiptera:
      Aphididae), a cosmopolitan group that feeds on plants in the genus Prunus
      (Rosaceae). Hyalopterus currently contains two recognized species associated with
      different Prunus species, although the taxonomy and evolutionary history of the
      group is poorly understood. Using mitochondrial COI sequences, 16S rDNA sequences
      from the aphid endosymbiont Buchnera aphidicola, and nine microsatellite loci we
      investigated population structure in Hyalopterus from the most commonly used
      Prunus host species throughout the Mediterranean as well as in California, where
      the species H. pruni is an invasive pest. We found three deeply divergent
      lineages structured in large part by specific associations with plum, almond, and
      peach trees. There was no evidence that geographic or temporal barriers could
      explain the overall diversity in the genus. Levels of genetic differentiation are
      consistent with that typically attributed to aphid species and indicate
      divergence times older than the domestication of Prunus for agriculture.
      Interestingly, in addition to their typical hosts, aphids from each of the three
      lineages were frequently found on apricot trees. Apricot also appears to act as a
      resource mediated hybrid zone for plum and almond associated lineages. Together,
      results suggest that host plants have played a role in maintaining host
      associated differentiation in Hyalopterus for as long as several million years,
      despite worldwide movement of host plants and the potential for ongoing
      hybridization.

PMID- 17542846
TI  - Museum specimens and phylogenies elucidate ecology's role in coevolutionary
      associations between mites and their bee hosts.
AB  - Coevolutionary associations between hosts and symbionts (or parasites) are often
      reflected in correlated patterns of divergence as a consequence of limitations on
      dispersal and establishment on new hosts. Here we show that a phylogenetic
      correlation is observed between chaetodactylid mites and their hosts, the long
      tongued bees; however, this association manifests itself in an atypical fashion.
      Recently derived mites tend to be associated with basal bee lineages, and vice
      versa, ruling out a process of cospeciation, and the existence of mites on
      multiple hosts also suggests ample opportunity for host shifts. An extensive
      survey of museum collections reveals a pattern of infrequent host shifts at a
      higher taxonomic level, and yet, frequent shifts at a lower level, which suggests
      that ecological constraints structure the coevolutionary history of the mites and
      bees. Certain bee traits, particularly aspects of their nesting behavior, provide
      a highly predictive framework for the observed pattern of host use, with 82.1% of
      taxa correctly classified. Thus, the museum survey and phylogenetic analyses
      provide a unique window into the central role ecology plays in this
      coevolutionary association. This role is apparent from two different perspectives
      -as (a) a constraining force evident in the historical processes underlying the
      significant correlation between the mite and bee phylogenies, as well as (b) by
      the highly nonrandom composition of bee taxa that serve as hosts to
      chaetodactylid mites.

PMID- 17542847
TI  - The evolutionary history of mycorrhizal specificity among lady's slipper orchids.
AB  - Although coevolution is acknowledged to occur in nature, coevolutionary patterns
      in symbioses not involving species-to-species relationships are poorly
      understood. Mycorrhizal plants are thought to be too generalist to coevolve with
      their symbiotic fungi; yet some plants, including some orchids, exhibit
      strikingly narrow mycorrhizal specificity. Here, we assess the evolutionary
      history of mycorrhizal specificity in the lady's slipper orchid genus,
      Cypripedium. We sampled 90 populations of 15 taxa across three continents, using
      DNA methods to identify fungal symbionts and quantify mycorrhizal specificity. We
      assessed phylogenetic relationships among sampled Cypripedium taxa, onto which we
      mapped mycorrhizal specificity. Cypripedium taxa associated almost exclusively
      with fungi within family Tulasnellaceae. Ancestral specificity appears to have
      been narrow, followed by a broadening after the divergence of C. debile.
      Specificity then narrowed, resulting in strikingly narrow specificity in most of
      the taxa in this study, with no taxon rewidening to the same extant as basal
      members of the genus. Sympatric taxa generally associated with different sets of
      fungi, and most clades of Cypripedium-mycorrhizal fungi were found throughout
      much of the northern hemisphere, suggesting that these evolutionary patterns in
      specificity are not the result of biogeographic lack of opportunity to associate
      with potential partners. Mycorrhizal specificity in genus Cypripedium appears to
      be an evolvable trait, and associations with particular fungi are
      phylogenetically conserved.

PMID- 17542848
TI  - Costs of resistance in the Drosophila-macrocheles system: a negative genetic
      correlation between ectoparasite resistance and reproduction.
AB  - Genetic variation for parasite resistance occurs in most host populations. Costs
      of resistance, manifested as reduced fitness of resistant genotypes in the
      absence of parasitism, can be an important factor contributing to the maintenance
      of this variation. One powerful tool for detecting costs of resistance is the
      study of correlated responses to artificial selection. Provided that experimental
      lines are recently derived from large outbreeding populations, and that
      inbreeding is minimized during the experiment, correlated responses to selection
      are expected to be strong indicators of pleiotropy. We artificially selected for
      elevated behavioral resistance against an ectoparasitic mite (Macrocheles
      subbadius) in replicate populations of the fly Drosophila nigrospiracula.
      Resistance was modeled as a threshold trait, and the realized heritability of
      resistance was estimated to be 12.3% (1.4% SE) across three replicate lines
      recently derived from nature. We contrasted the longevity and fecundity of
      resistant and control (unselected) flies under a variable thermal environment. We
      report that reduced fecundity is a correlated response to artificial selection
      for increased resistance, and that the strength of this effect increases from 25
      degrees to 29 degrees C. In contrast, longevity differences were not detected
      between resistant and control lines at either temperature. These findings are
      robust as they were confirmed with an independent set of experimental lines.
      Thus, our results identify a negative genetic correlation between ectoparasite
      resistance and an important life-history trait. That a correlated response was
      only detected for fecundity, and not longevity, suggests that the genetic
      correlation is attributable to pleiotropic effects with narrower effects than
      reallocation of a general resource pool within the organism, although other
      interpretations are discussed. Combined with fluctuating parasite-mediated
      selection and temperature, the presence of this trade-off may contribute to the
      maintenance of genetic variation for resistance in natural populations.

PMID- 17542849
TI  - Mapping quantitative trait Loci underlying fitness-related traits in a free
      living sheep population.
AB  - We searched for quantitative trait loci (QTL) underlying fitness-related traits
      in a free-living pedigree of 588 Soay sheep in which a genetic map using 251
      markers with an average spacing of 15 cM had been established previously. Traits
      examined included birth date and weight, considered both as maternal and
      offspring traits, foreleg length, hindleg length, and body weight measured on
      animals in August and jaw length and metacarpal length measured on cleaned
      skeletal material. In some cases the data were split to consider different age
      classes separately, yielding a total of 15 traits studied. Genetic and
      environmental components of phenotypic variance were estimated for each trait
      and, for those traits showing nonzero heritability (N= 12), a QTL search was
      conducted by comparing a polygenic model with a model including a putative QTL.
      Support for a QTL at genome-wide significance was found on chromosome 11 for jaw
      length; suggestive QTL were found on chromosomes 2 and 5 (for birth date as a
      trait of the lamb), 8 (birth weight as a trait of the lamb), and 15 (adult
      hindleg length). We discuss the prospects for refining estimates of QTL position
      and effect size in the study population, and for QTL searches in free-living
      pedigrees in general.

PMID- 17542850
TI  - Mitonuclear discordance is caused by rampant mitochondrial introgression in
      Neodiprion (Hymenoptera: Diprionidae) sawflies.
AB  - We investigate the pervasiveness of hybridization and mitochondrial introgression
      in Neodiprion Rohwer (Hymenoptera; Diprionidae), a Holarctic genus of conifer
      feeding sawflies. A phylogenetic analysis of the lecontei species group revealed
      extensive discordance between a contiguous mitochondrial region spanning three
      genes (COI, tRNA-leucine, and COII) and three nuclear loci (EF1alpha, CAD, and an
      anonymous nuclear locus). Bayesian tests of monophyly and Shimodaira-Hasegawa
      (SH) tests of topological congruence were consistent with mitochondrial
      introgression; however, these patterns could also be explained by lineage sorting
      (i.e., deep coalescence). Therefore, to explicitly test the mitochondrial
      introgression hypothesis, we used a novel application of coalescent-based
      isolation with migration (IM) models to measure interspecific gene flow at each
      locus. In support of our hypothesis, mitochondrial gene flow was consistently
      higher than nuclear gene flow across 120 pairwise species comparisons (P < 1 x
      10(-12)). We combine phylogenetic and coalescent evidence to identify likely
      cases of recent and ancient introgression in Neodiprion, and based on these
      observations, we hypothesize that shared hosts and/or pheromones facilitate
      hybridization, whereas disparate abundances between hybridizing species promote
      mitochondrial introgression. Our results carry implications for phylogenetic
      analysis, and we advocate the separation of high and low gene flow regions to
      inform analyses of hybridization and speciational history, respectively.

PMID- 17542851
TI  - Integrating coalescent and ecological niche modeling in comparative
      phylogeography.
AB  - Understanding the factors that contribute to the formation of population genetic
      structure is a central goal of phylogeographic research, but achieving this goal
      can be complicated by the stochastic variance inherent to genetic processes.
      Statistical approaches to testing phylogeographic hypotheses accommodate this
      stochasticity by evaluating competing models of putative historical population
      structure, often by simulating null distributions of the expected variance. The
      effectiveness of these tests depends on the biological realism of the models.
      Information from the fossil record can aid in reconstructing the historical
      distributions of some taxa. However, for the majority of taxa, which lack
      sufficient fossils, paleodistributional modeling can provide valuable spatial
      geographic data concerning ancestral distributions. Paleodistributional models
      are generated by projecting ecological niche models, which predict the current
      distribution of each species, onto a model of past climatic conditions. Here, we
      generate paleodistributional models describing the suitable habitat during the
      last glacial maximum for lineages from the mesic forests of the Pacific Northwest
      of North America, and use these models to generate alternative phylogeographic
      hypotheses. Coalescent simulations are then used to test these hypotheses to
      improve our understanding of the historical events that promoted the formation of
      population genetic structure in this ecosystem. Results from Pacific Northwest
      mesic forest organisms demonstrate the utility of these combined approaches.
      Paleodistribution models and population genetic structure are congruent across
      three amphibian lineages, suggesting that they have responded in a concerted
      manner to environmental change. Two other species, a willow and a water vole,
      despite being currently codistributed and having similar population genetic
      structure, were predicted by the paleodistributional model to have had markedly
      different distributions during the last glacial maximum. This suggests that
      congruent phylogeographic patterns can arise from incongruent ancestral
      distributions. Paleodistributional models introduce a much-needed spatial
      geographic perspective to statistical phylogeography. In conjunction with
      coalescent models of population genetic structure, they have the potential to
      improve our understanding of the factors that promote population divergence and
      ultimately produce regional patterns of biodiversity.

PMID- 17542852
TI  - Quantitatively comparing morphological trends to environment in the fossil record
      (Cincinnatian series; Upper Ordovician).
AB  - Determining whether morphological trends in fossil species represent evolution
      within a lineage or lateral shifts in morphologically variable populations
      through time requires a thorough examination of the details of both morphology
      and paleoenvironment in time and space. The purpose of this study is to explore
      at high resolution the relationship between morphology of the trilobite
      Flexicalymene granulosa and paleoenvironmental conditions in Upper Ordovician
      deposits of southwestern Ohio and northern Kentucky. This is achieved by using
      geometric morphometrics to measure high-resolution morphological changes and by
      using gradient analysis to capture environmental gradients underlying faunal
      distribution patterns. Quantitatively comparing the outcomes of these two
      techniques provides an assessment of whether shape changes relates to
      environment. Results indicate that a significant amount of shape change, seen as
      an anteromedial movement of the eye region over time, corresponds to ordination
      scores. This suggests a relationship between certain aspects of morphology and
      environment. The combination of these quantitative techniques has provided the
      foundation for determining whether morphological trends within F. granulosa
      represent evolution or temporal shifts in geographic variation. Future work will
      involve examining this relationship in greater detail both geographically and
      stratigraphically.

PMID- 17542853
TI  - The automation and evaluation of nested clade phylogeographic analysis.
AB  - Nested clade phylogeographic analysis (NCPA) is a popular method for
      reconstructing the demographic history of spatially distributed populations from
      genetic data. Although some parts of the analysis are automated, there is no
      unique and widely followed algorithm for doing this in its entirety, beginning
      with the data, and ending with the inferences drawn from the data. This article
      describes a method that automates NCPA, thereby providing a framework for
      replicating analyses in an objective way. To do so, a number of decisions need to
      be made so that the automated implementation is representative of previous
      analyses. We review how the NCPA procedure has evolved since its inception and
      conclude that there is scope for some variability in the manual application of
      NCPA. We apply the automated software to three published datasets previously
      analyzed manually and replicate many details of the manual analyses, suggesting
      that the current algorithm is representative of how a typical user will perform
      NCPA. We simulate a large number of replicate datasets for geographically
      distributed, but entirely random-mating, populations. These are then analyzed
      using the automated NCPA algorithm. Results indicate that NCPA tends to give a
      high frequency of false positives. In our simulations we observe that 14% of the
      clades give a conclusive inference that a demographic event has occurred, and
      that 75% of the datasets have at least one clade that gives such an inference.
      This is mainly due to the generation of multiple statistics per clade, of which
      only one is required to be significant to apply the inference key. We survey the
      inferences that have been made in recent publications and show that the most
      commonly inferred processes (restricted gene flow with isolation by distance and
      contiguous range expansion) are those that are commonly inferred in our
      simulations. However, published datasets typically yield a richer set of
      inferences with NCPA than obtained in our random-mating simulations, and further
      testing of NCPA with models of structured populations is necessary to examine its
      accuracy.

PMID- 17542854
TI  - Male courtship song and female preference variation between phylogeographically
      distinct populations of Drosophila montana.
AB  - Understanding the variation within and between populations in important male
      mating traits and female preferences is crucial to theories concerning the origin
      of sexual isolation by coevolution or other processes. There have been
      surprisingly few studies on the extent of variation and covariation within and
      between populations, especially where the evolutionary relationships between
      populations are understood. Here we examine variation in female preferences and a
      sexually selected male song trait, the carrier frequency of the song, within and
      between populations from different phylogeographic clusters of Drosophila
      montana. Song is obligatory for successful mating in this species, and both
      playback and field studies implicate song carrier frequency as the most important
      parameter in male song. Carrier frequency varied among three recently collected
      populations from Oulanka (Finland), Vancouver (Canada), and Colorado (central
      United States), which represent the main phylogeographic groups in D. montana.
      Males from Colorado had the most distinct song frequency, which did not follow
      patterns of genetic differentiation. There was considerable variation in
      preference functions within, and some variation between, populations.
      Surprisingly, females from three lines from Colorado seem to have preferences
      disfavoring the extreme male trait found in this population. We discuss sources
      of selection on male song and female preference.

PMID- 17542855
TI  - Male scorpionflies assess the amount of rival sperm transferred by females'
      previous mates.
AB  - Theory predicts that when sperm compete numerically, selection will favor males
      who vary the number of sperm they transfer with the immediate level of sperm
      competition. In this study, I measured male mating investment in response to both
      female mating status (virgin vs. mated) and the number of foreign sperm stored by
      females in a previous mating in the scorpionfly Panorpa cognata. Female sperm
      storage was manipulated by interrupting copulations at different time points.
      Female mating status did not significantly influence male mating investment, but
      resource-limited males invested strategically in relation to the amount of sperm
      stored by females in a previous mating. I found continuously decreasing male
      investment in response to increasing amounts of competing sperm. These results
      demonstrate an unprecedented male ability to assess the number of sperm stored by
      females. As a result, males are capable of an extraordinarily fine-tuned reaction
      to the intensity of sperm competition.

PMID- 17542856
TI  - A negative relationship between mutation pleiotropy and fitness effect in yeast.
AB  - It is generally thought that random mutations will, on average, reduce an
      organism's fitness because resulting phenotypic changes are likely to be
      maladaptive. This relationship leads to the prediction that mutations that alter
      more phenotypic traits, that is, are more pleiotropic, will impose larger fitness
      costs than mutations that affect fewer traits. Here we present a systems approach
      to test this expectation. Previous studies have independently estimated fitness
      and morphological effects of deleting all nonessential genes in Saccharomyces
      cerevisiae. Using datasets generated by these studies, we examined the
      relationship between the pleiotropic effect of each deletion mutation, measured
      as the number of morphological traits differing from the parental strain, and its
      effect on fitness. Pleiotropy explained approximately 18% of variation in fitness
      among the mutants even once we controlled for correlations between morphological
      traits. This relationship was robust to consideration of other explanatory
      factors, including the number of protein-protein interactions and the network
      position of the deleted genes. These results are consistent with pleiotropy
      having a direct role in affecting fitness.

PMID- 17542857
TI  - Museums teach evolution.
AB  - Natural history museums play a significant role in educating the general public
      about evolution. This article describes Explore Evolution, one of the largest
      evolution education projects funded by the National Science Foundation. A group
      of regional museums from the Midwestern United States worked with leading
      evolutionary scientists to create multiple permanent exhibit galleries and a
      curriculum book for youth. This program invites the public to experience current
      evolutionary research on organisms that range in size from HIV to whales.
      Learning research is being conducted on museum visitors to understand how they
      reason about evolution and to determine what influences the process of conceptual
      change.

PMID- 17542859
TI  - Contamination: nursing diagnoses with outcome and intervention linkages.
AB  - PURPOSE: To relate the collaborative processes involved in the evolution of
      environmental nursing diagnoses and the linkages between two new nursing
      diagnoses and their associated interventions and outcomes; to describe the
      environmental health implications of contamination. DATA SOURCES: Published
      research articles, official reports, textbooks, and collaborative discussion with
      experts in community and global health. DATA SYNTHESIS: Reflection following
      review of the literature and collaboration with experts led to the development of
      a new schema for environmental diagnoses and development of two new diagnoses,
      allowing for greater clarity and distinction between the contamination diagnoses
      and risk for poisoning diagnosis. CONCLUSIONS: An environmental nursing diagnosis
      schema, with its emphasis on contamination, infection, and violence, provides
      nurses with a holistic framework for making judgments about environmental
      influences related to individual, family, community, and global health. The
      diagnoses of Contamination and Risk for Contamination provide necessary language
      to describe human responses and risk states that may arise following exposure to
      environmental contaminants. PRACTICE IMPLICATIONS: Development of environmental
      diagnostic labels and delineation of the linkages to nursing outcomes and
      interventions will allow nurses to take active roles in identifying environmental
      components that affect health and planning care that responds to environmental
      health needs. Greater clarity in the use of language will allow nurses to
      incorporate environmental concepts appropriately in nursing assessments and
      improve the accuracy of the diagnostic process and selection of distinct
      interventions and outcomes. This will result in better outcomes for patients and
      communities and permit greater accountability of nursing's contribution to
      environmental health.

PMID- 17542860
TI  - Is it time for a new category of nursing diagnosis?
AB  - Professional vigilance, the art of "watching out," is the essence of nursing.
      Vigilance is the mental process that makes the informed nursing actions of
      assessment, diagnosis, intervention, and evaluation possible and meaningful.
      Nursing vigilance must be described in our nursing terminology or it risks
      remaining invisible to others. We propose that the current definition of nursing
      diagnosis be expanded to include surveillance diagnoses for which the nurse has
      the responsibility for problem identification and ongoing monitoring. Inclusion
      of surveillance diagnoses in the NANDA International taxonomy will better reflect
      the breadth and depth of nursing practice.

PMID- 17542861
TI  - Viewpoint: use of King's conceptual system, nursing informatics, and nursing
      classification systems for global communication.
AB  - PURPOSE: To propose a common nursing language for communication among members of
      the nursing community worldwide. DATA SOURCES: The Taxonomy of Nursing Practice,
      nursing informatics literature, King's Theory of Goal Attainment applied to the
      nursing process. DATA SYNTHESIS: Several milestones in nursing in the 20th
      century indicated the need for a universal language for nursing. The nursing
      process provides a method for synthesis of nursing data, information, and
      knowledge and is congruent with Imogene King's Theory of Goal Attainment.
      CONCLUSIONS: The authors advocate for a common nursing language (nursing
      classification and terminology systems) that would unify nurses worldwide.
      Supported by nursing theory and technology, global communication would be
      enhanced for nurses and the interdisciplinary teams of which they are a part.
      IMPLICATIONS FOR PRACTICE: Use of Imogene King's Conceptual System and Theory of
      Goal Attainment and the nursing specialty of Nursing Informatics are examples of
      nursing theory and technology to frame global communication.

PMID- 17542862
TI  - Concept comparison of caring and social support.
AB  - PURPOSE: To explicate the similarities and differences between the concepts of
      caring and social support. METHODS: Qualitative concept comparison. FINDINGS:
      Similarities and/or subtle and substantive differences exist between caring and
      social support. Both concepts are characterized as dynamic interpersonal
      processes that involve sensitivity. Caring appears to lie within the purview of
      expert nurse providers, while social support is located primarily within the
      domain of lay providers. Social support is perfunctory and focused, whereas
      caring encounters are more intimate and holistic. Caring results in improved
      mental well-being for both recipients and providers, while improvements in mental
      health are limited to social support recipients. Unlike social support, physical
      well-being is an outcome of caring. CONCLUSIONS: Caring and social support share
      common attributes and outcomes; however, they appear to be different processes
      that predominately exist in separate domains. Caring appears to reside within the
      professional paradigm of nursing, while social support exists primarily within
      the sphere of lay providers. IMPLICATIONS: Nurses are encouraged to develop and
      use well-delineated conceptual frameworks to guide practice and research.

PMID- 17542865
TI  - Linear and whorled hypermelanosis.
AB  - Linear and whorled nevoid hypermelanosis is a sporadic pigmentary anomaly
      occurring within the first weeks of life, characterized clinically by swirls and
      streaks of macular hyperpigmentation following the lines of Blaschko.
      Histologically it shows only epidermal melanosis. Underlying chromosomal
      mosaicism has been demonstrated in only a few published cases. Progressive
      cribriform and zosteriform hyperpigmentation is considered to be the localized
      variant of linear and whorled nevoid hypermelanosis. We report a retrospective
      study on 16 children referred consecutively over a 10-year period for evaluation
      of segmental, linear or swirled hyperpigmentation distributed along the lines of
      Blashko, consistent with a diagnosis of linear and whorled nevoid hypermelanosis.
      Associated abnormalities were found only in one out of six patients with the
      diffuse form (linear and whorled nevoid hypermelanosis-type) and in none of the
      remaining 10 children presenting the unilateral form (progressive cribriform and
      zosteriform hyperpigmentation-type). A long-term follow-up did not disclose
      further abnormalities. The authors discuss the nosologic position of this entity
      with respect to hypomelanosis of Ito. Linear and whorled nevoid hypermelanosis
      and hypomelanosis of Ito should be not considered single entities, but be rather
      grouped as a heterogeneous collection of nonspecific pigmentary disorders caused
      by genetic mosaicism. Skin findings in these diseases can differ according to the
      pigmentation in the normal cell line and whether the second line contains more or
      less melanosomes than the normal skin of the individual exhibiting mosaicism.

PMID- 17542866
TI  - Perforating neutrophilic and granulomatous dermatitis of the newborn--a clue to
      immunodeficiency.
AB  - We report two newborns with a widespread cutaneous eruption consisting of
      discrete papules which evolved into vesicles, pustules, crusts, and ulcers. These
      healed over a 2-week period with scarring. Histopathology showed three main
      features--histiocytic granulomas, neutrophilic infiltration, and transepidermal
      elimination of degenerated collagen and debris through hair follicles. Both
      patients had congenital immunodeficiency. This skin condition of the newborn,
      with distinct clinical and histopathologic features, is a manifestation of
      immunodeficiency that has not been previously described.

PMID- 17542867
TI  - Tanning device usage: what are parents thinking?
AB  - Tanning device usage is prevalent among adolescents. Few studies have assessed
      the role of parental influence on children's use of indoor tanning facilities.
      Our objective was to determine if children's tanning device usage is affected by
      parental knowledge of risks of indoor tanning or by parental tanning practices. A
      survey was administered to 160 parents of 328 children at a general pediatrics
      clinic and 204 parents of 367 children at a pediatric dermatology clinic (parents
      n=364, children n=695). Over half of all parents and 17% of all teenagers queried
      had previously used tanning devices. The level of parental knowledge did not
      predict tanning device usage by their children. However, parental tanning device
      usage was associated with increased usage by children (p<0.05). Children began
      using tanning devices on average more than 4 years earlier than their parents.
      Most parents (69%) never wanted their children to use tanning devices, but only
      15% of parents had discussed them with their children. Therefore, health
      providers can provide an important service by initiating discussions about
      tanning devices. Additional measures, including legislation requiring parental
      consent for indoor tanning, are needed to reduce tanning device usage by minors.

PMID- 17542868
TI  - Randomized trial on sun safety education at ski and snowboard schools in western
      North America.
AB  - The purpose of this study was to evaluate the effectiveness of Go Sun Smart, a
      sun safety education program, directed to parents and children enrolled in ski
      and snowboard schools at high altitude resorts in western North America. Twenty
      six ski resorts were paired and then randomly assigned to the intervention or
      control condition. Three hundred fifty-seven parents were interviewed about their
      children's sun safety behavior and exposure to the Go Sun Smart program. More
      parents at the intervention resorts reported that their child was wearing
      sunscreen than at the control resorts (OR 2.37, 95% CI 0.93, 5.99) but this
      result was significant only at resorts in the Northwest region (OR 2.72, 95% CI
      1.24, 5.95). Parents at intervention resorts had significantly increased odds of
      having seen a Go Sun Smart poster than those at the control resorts (OR=8.53, 95%
      CI 2.17, 33.54). No significant differences were identified between the
      intervention and control groups for verbal messages from ski resort employees
      about sun protection. Outdoor wintertime recreation venues are a potentially
      effective site from which to implement sun safety education programs for children
      and parents.

PMID- 17542869
TI  - Familial homozygous hypercholesterolemia: report of two patients and review of
      the literature.
AB  - Familial homozygous hypercholesterolemia is a rare autosomal dominant, metabolic
      disorder caused by mutation in the gene, which encodes the synthesis of low
      density lipoprotein receptors and is characterized by increased serum low-density
      lipoprotein cholesterol. Multiple types of xanthomas occur, such as tendinous,
      tuberous, xanthelasma, and sub-periosteal. Intertriginous xanthomas are rare but
      if present are pathognomonic of this disorder. We report two children with
      familial homozygous hypercholesterolemia who had multiple xanthomas including the
      intertriginous variety.

PMID- 17542870
TI  - Mohs surgical treatment of a granular cell tumor on the toe of a child.
AB  - Granular cell tumors are uncommon, usually benign tumors of neural origin. They
      are most often diagnosed in the third to sixth decades of life and are
      infrequently seen in the pediatric population. Although they can be found in a
      wide distribution throughout the body, more than half occur in the oral cavity
      and other head and neck sites such as the larynx. We report a granular cell tumor
      on the distal toe of a 5-year-old child, removed with Mohs surgery. Review of the
      English language literature revealed four previously reported granular cell
      tumors treated with Mohs micrographic surgery, none of which was in a child.

PMID- 17542871
TI  - Multiple juvenile xanthogranulomas in a 13-year-old.
AB  - A 13-year-old Caucasian girl presented with a 1(1/2) month history of multiple,
      asymptomatic, discrete, orange-yellow to skin-colored, dome-shaped, smooth, 3 to
      6 mm papules on the arms, legs, trunk, and buttock. Pathology showed a dermal
      infiltrate of Touton-type giant cells, scattered lymphocytes, and macrophages.
      The patient was diagnosed with juvenile xanthogranuloma. We present this patient
      because of the uncommon presentation of multiple juvenile xanthogranulomas in a
      13-year-old. Although juvenile xanthogranuloma generally occurs in infancy, it
      must be included in the differential diagnosis for an older child. This entity
      can less frequently occur in adults and typically a solitary lesion is found.
      Multiple juvenile xanthogranuloma is rare in older children and adults. Work-up
      should include a thorough review of systems, physical examination, and
      ophthalmology examination. Pediatricians and dermatologists should be aware that
      juvenile xanthogranulomas might occur in older children.

PMID- 17542872
TI  - The nasal crease sign in segmental facial hemangioma--an early sign of cartilage
      destruction.
AB  - Although the majority of hemangiomas of infancy do not require treatment, a
      subset of patients have complications such as ulceration, functional impairment
      or severe disfigurement that necessitate intervention. It is often difficult to
      predict which hemangiomas will lead to permanent disfigurement and medical
      complications. We present three patients with segmental facial hemangiomas
      involving the nose which resulted in nasal cartilage destruction. All three
      patients had a linear gray atrophic crease in the inferior columella visualized
      on clinical examination prior to the onset of nasal collapse. We propose that
      this ''nasal crease sign'' in infants with segmental facial hemangioma involving
      the nose and philtrum may be a premonitory clinical finding of impending nasal
      cartilage destruction. Dermatologists should be aware of this clinical sign which
      may help identify patients at high risk of nasal destruction. Unfortunately,
      aggressive medical intervention may not always prevent devastating disfigurement.

PMID- 17542873
TI  - Hyperthyroidism and lupus-like syndrome in an adolescent treated with minocycline
      for acne vulgaris.
AB  - Minocycline is a tetracycline antibiotic commonly used in the treatment of acne.
      While it is generally considered to be a safe medicine, a number of side effects
      have been associated with its use. We describe an adolescent boy who developed
      hyperthyroidism and a drug-induced lupus-like syndrome following minocycline
      treatment for his acne.

PMID- 17542874
TI  - Localized hypertrichosis in a pediatric patient--what is the mechanism for excess
      hair growth?
AB  - Localized hypertrichosis is an uncommon complaint among pediatric dermatology
      patients. We highlight an instance of localized hypertrichosis due to an
      underlying diffuse neurofibroma in a patient with known neurofibromatosis 1. The
      classification and possible underlying pathogenic mechanisms of localized
      hypertrichosis in pediatric patients is discussed.

PMID- 17542875
TI  - Acquired mucosal indeterminate cell histiocytoma.
AB  - Indeterminate cell histiocytosis is an exceptional and controversial entity with
      variable clinical, histopathologic or immunohistochemical findings, sharing
      morphologic and immunophenotypic features from both Langerhans and non-Langerhans
      cell histiocytoses. Neoplastic cells express S-100 and CD1a antigens, but lack
      Birbeck granules. It has been reported in both adults and children, as solitary
      or multiple cutaneous lesions with rare extracutaneous involvement. We describe a
      12-year-old boy with an indeterminate cell histiocytosis manifesting as a
      solitary verrucous papule on the mucosa of the glans penis. The morphologic
      features and diagnostic criteria of cutaneous indeterminate cell histiocytic
      proliferations are reviewed. The possible relationship between indeterminate cell
      and Langerhans cell histiocytoses is discussed.

PMID- 17542876
TI  - Primary cutaneous zygomycosis in two immunocompromised children.
AB  - Zygomycosis, often referred to as ''mucormycosis'' or ''phycomycosis,'' is a
      rapidly progressive fungal infection which usually occurs in immunocompromised
      individuals, and is characterized by soft tissue destruction and invasion of
      blood vessels. The rare and easily misdiagnosed primary cutaneous form may
      present as a superficial erosion with a painless, gradual onset and slow
      progression of symptoms or a gangrenous, necrotic ulceration due to rapid tissue
      and vascular invasion. With the latter form, the mortality rate among affected
      individuals is high even after aggressive surgical debridement and amphotericin B
      administration, emphasizing the importance of early recognition and proper
      diagnosis. We present two instances of gangrenous cutaneous zygomycosis in
      immunocompromised children and review the literature with regard to etiology,
      diagnosis and treatment, highlighting the pediatric population.

PMID- 17542877
TI  - Congenital cranial fasciitis--''watch and wait'' or early intervention.
AB  - Cranial fasciitis is a rare variant of nodular fasciitis of childhood, a benign
      condition cured by surgical excision. Recently, spontaneous involution has been
      reported and a ''watch and wait'' approach was recommended. We report an instance
      of a congenital cranial fasciitis that grew rapidly during a 10-month follow-up
      after fine needle aspiration and incisional biopsy. Conservative surgical
      excision was curative with no recurrence over a follow-up period of 4 years.
      Therefore, we recommend that early excision may be necessary in lieu of a ''watch
      and wait'' approach for large, rapidly growing cranial fasciitis.

PMID- 17542878
TI  - Hypohidrotic ectodermal dysplasia and intrathoracic neuroblastoma.
AB  - We report a 6-year-old girl with a subtle form of hypohidrotic ectodermal
      dysplasia and a phenotype consisting of curly hair, a round face, a stocky build,
      and obesity, which was associated with intrathoracic neuroblastoma. Although this
      new association could be a chance occurrence, its description may alert
      physicians to look for similar combinations and report these, as it may lead to
      better syndrome delineation, and patient care.

PMID- 17542879
TI  - Diffuse acute pustular eruption after streptococcal infection--a new instance of
      pustulosis acuta generalisata.
AB  - We report a 6-year-old boy with a diffuse acute pustular eruption which appeared
      after an erysipela. On the basis of the history and clinical features we made a
      diagnosis of pustulosis acuta generalisata. An 8-day antibiotic course with
      amoxicillin and clavulanic acid was instituted. After 1 week the erysipela and
      the pustular eruption had healed and no relapse of the rash occurred in the
      following month.

PMID- 17542880
TI  - Prurigo pigmentosa associated with an atopic diathesis in a 13-year-old girl.
AB  - We report an Italian prepubescent girl with the typical clinical and histologic
      features of prurigo pigmentosa associated with an atopic diathesis. The
      dermatitis disappeared after treatment with minocycline, leaving a brown,
      reticulated hyperpigmentation, with no recurrence. The association with an atopic
      diathesis could justify, in this instance, the major susceptibility to
      environmental factors claimed by some authors as triggering factors for prurigo
      pigmentosa. To our knowledge, this is only the second occurrence of this disease
      in a prepubescent patient reported in the literature.

PMID- 17542881
TI  - Further documentation of spontaneous regression of infantile digital
      fibromatosis.
AB  - Infantile digital fibromatosis is a rare benign fibromatous tumor characterized
      by both its location on fingers and toes and its distinctive light microscopic
      appearance. However, treatment modalities are not yet standardized. Surgical
      excision had been preferred in the past but has the disadvantage of a high
      recurrence rate. More recently, isolated instances of spontaneous regression have
      been reported with a short follow-up. We report four children with infantile
      digital fibromatosis, who underwent spontaneous regression after clinical
      monitoring and long-term follow-up. We recommend regular follow-up in order to
      allow for intervention in case of functional impact on the affected extremities.

PMID- 17542882
TI  - Localized cutaneous Cryptococcus albidus infection in a 14-year-old boy on
      etanercept therapy.
AB  - Immune-modulating medications, such as the tumor necrosis factor-alpha
      inhibitors, are establishing a niche in the dermatologic therapeutic
      armamentarium as novel, effective, and relatively safe alternatives in the
      treatment of numerous inflammatory dermatoses. The benefits of anti-tumor
      necrosis factor-alpha inhibitor therapy are well known. However, these agents are
      also associated with an increased risk of infectious complications--most commonly
      granulomatous infections with mycobacteria and fungi. We present a teenaged boy
      with localized, cutaneous Cryptococcus albidus infection on the scalp which
      occurred after he began etanercept for refractory psoriasis. The infection
      resolved after a course of fluconazole. This is the second report of localized,
      cutaneous C. albidus infection, but the first occurring in association with
      etanercept therapy. Our patient's findings remind us that extra vigilance is
      imperative in monitoring patients on immunosuppressive regimens and that any
      persistent, nonhealing lesion in these patients should prompt evaluation for
      potential infection, not only from common and typical pathogens but also from
      more unusual, atypical ones.

PMID- 17542883
TI  - Effect of desonide hydrogel 0.05% on the hypothalamic-pituitary-adrenal axis in
      pediatric subjects with moderate to severe atopic dermatitis.
AB  - Desonide, a low potency corticosteroid, has been used widely as a topical
      treatment for inflammatory dermatoses for over 30 years. A recent formulation
      advance has enabled the development of desonide 0.05% into a novel moisturizing
      aqueous gel (hydrogel) that is free of alcohol and surfactants. This multicenter,
      open-label study evaluated the hypothalamic-pituitary-adrenal axis suppression
      potential, tolerability, and efficacy of this new Class VI topical steroid
      formulation in pediatric subjects with moderate-to-severe atopic dermatitis (mean
      body surface area = 51%). Forty children, aged 6 months to 6 years were enrolled
      and treated twice daily for 4 weeks. Desonide hydrogel 0.05% was well tolerated
      and no treatment-related adverse events were reported. No suppression of adrenal
      function was observed in subjects who completed the study without protocol
      violations related to cosyntropin administration or cortisol testing (n=34). Of
      the subjects who completed the study with complications in cortisol testing
      (n=3), there was one subject (1/37=3%) who had a low poststimulation cortisol
      level at week 4. Efficacy was demonstrated by marked improvement in overall
      disease state and in the signs and symptoms of atopic dermatitis. This study
      validates the systemic safety of a novel desonide hydrogel formulation in young
      pediatric patients and confirms the longstanding tolerability and efficacy
      profile of desonide.

PMID- 17542884
TI  - Synthetic tannins in dermatology--a therapeutic option in a variety of pediatric
      dermatoses.
AB  - Synthetic tannins are established adjuvants in the therapy of itchy, inflamed,
      weeping, superficial skin diseases. The therapeutic effects of synthetic tannins
      are based on their tanning action as well as on their antimicrobial, anti
      inflammatory, and antipruritic effects. In terms of pharmacology and clinical
      applicability, synthetic tannins are particularly versatile substances. They have
      also been used as steroid-free, anti-inflammatory treatment alternatives,
      especially in pediatric dermatoses. Systemic absorption is not to be expected.
      Because of their high safety profile and good tolerance, they are appropriate for
      the treatment of all age groups. Thus, synthetic tannins can be safely used for
      infants and children and also during pregnancy and lactation.

PMID- 17542885
TI  - Support groups for children and their families in pediatric dermatology.
AB  - Recent discussions regarding the burden of skin disease and patient-centered
      medicine highlight the profound effects skin disease can have on individuals,
      their families, and society as a whole. Local support groups, often connected to
      national patient advocacy groups, can be an invaluable resource for patients, and
      offer physicians the opportunity to learn more about patients' disease
      experiences while providing adjunctive therapy for conditions such as alopecia
      areata and vitiligo, for which medical options are often limited. We created a
      support group for children with alopecia areata and their parents as a model for
      other diseases such as vitiligo and epidermolysis bullosa. Herein we outline the
      steps involved in establishing a support group, including the many resources
      available for patient support, steps in the recruitment of patients, topics for
      discussion and goals for the group, and the logistics of running a meeting.
      Creating this family support group was a relatively straightforward and rewarding
      experience for us, and we hope that other pediatric dermatologists can utilize
      this model for their patients.

PMID- 17542886
TI  - What syndrome is this? Laryngo-onycho-cutaneous syndrome.

PMID- 17542887
TI  - What syndrome is this? Kabuki make-up syndrome.

PMID- 17542888
TI  - What syndrome is this? Oculocerebral hypopigmentation syndrome of preus.

PMID- 17542889
TI  - Gravitational erythema.
AB  - We report an extremely unusual instance of macular erythema on the arms of a 15
      year-old boy that occurs when the arms are in a dependent position. The eruption
      disappears promptly on elevation of the arms. The skin changes observed in our
      patient are similar to those previously described under the term gravitational
      erythema. It is suggested that the cutaneous lesions are secondary to an abnormal
      response to changes in venous pressure.

PMID- 17542890
TI  - Mucocutaneous findings in 100 children with Down syndrome.
AB  - Down syndrome is the most common chromosomal abnormality affecting numerous
      organs, including the skin. Our aim was to study mucocutaneous findings in this
      syndrome. To do so, 100 children with Down syndrome attending Schools for
      Children with Special Educational Needs and centers affiliated to the Welfare and
      Rehabilitation Organization in two provinces of Iran were thoroughly examined for
      skin and mucosal lesions. Their mean age was 11.2 years (3-20 years).
      Mucocutaneous findings were noted in 61. These were as follows (in decreasing
      order)--fissured tongue 28%, hypertrophy of tongue papilla 22%, premature graying
      14%, cheilitis 13%, xerosis 12%, alopecia areata 11%, palmoplantar hyperkeratosis
      10%, syringoma 6%, keratosis pilaris 4%, geographic tongue 4%, trichotillomania
      4%, vitiligo 3%, seborrheic dermatitis 3%, livedo reticularis 2%. No instances of
      atopic dermatitis or skin infections and infestations were noted. The lack of
      atopic dermatitis in our series was in concordance with its low prevalence
      reported in recent articles. Improved hygiene due to patient care at home may
      underlie the absence of infections. With the increasing survival rate of those
      with Down syndrome, physicians should be more aware of the skin findings seen so
      frequently in this genetic disorder.

PMID- 17542891
TI  - Cutis marmorata telangiectatica congenita and neonatal lupus.
AB  - Cutis marmorata telangiectatica congenita is an uncommon congenital vascular
      anomaly that is characterized by persistent, reticulated, violaceous
      pigmentation. We describe a female infant with vascular lesions consistent with
      this entity who was born to a mother with previously diagnosed systemic lupus
      erythematosus. Antinuclear antibodies and anti-Ro/SSA antibodies were detected in
      both mother and infant, supporting a diagnosis of neonatal lupus. This
      presentation is consistent with the rarely reported association between neonatal
      lupus and cutis marmorata telangiectatica congenita that suggests the latter is
      part of the cutaneous spectrum of the former. A thorough maternal history and
      laboratory investigations should be considered for infants with cutis marmorata
      telangiectatica congenita and their mothers in order to rule out the presence of
      an underlying autoimmune disease.

PMID- 17542892
TI  - Psoriasiform lesions and abscesses as initial manifestations of severe
      hypothyroidism in a previously healthy 15-year-old girl.
AB  - Hypothyroidism is associated with many characteristic cutaneous manifestations;
      however, to the best of our knowledge, it has not previously been linked to
      psoriasiform lesions or multiple abscesses. We describe a previously healthy 15
      year-old girl with psoriasiform lesions, abscesses, and extremely severe
      hypothyroidism, all presenting simultaneously. The pathophysiology of the
      connection is unclear, but several hypotheses are discussed. The temporal
      relationship of these conditions and the significant improvement of the skin
      lesions upon normalization of T4 levels following initiation of thyroid
      supplementation illustrate a direct association. It is probable that the extreme
      severity of hypothyroidism in our patient is implicated in the etiology of these
      skin lesions. This unique case illustrates that novel cutaneous manifestations
      may sometimes act as an early presenting sign of hypothyroidism and may be
      associated with more severe forms of the disorder.

PMID- 17542893
TI  - Familial chylomicronemia syndrome.
AB  - Familial chylomicronemia syndrome is a rare disorder of lipoprotein metabolism
      due to familial lipoprotein lipase (LPL) or apolipoprotein C-II deficiency or the
      presence of inhibitors to lipoprotein lipase. It manifests as eruptive xanthomas,
      acute pancreatitis, and lipaemic plasma due to marked elevation of triglyceride
      and chylomicron levels. We report two siblings with this rare disorder and review
      the literature.

PMID- 17542894
TI  - Bullous lesions in Henoch-Schonlein purpura.
AB  - Henoch-Schonlein purpura (HSP) is a small-vessel vasculitis characterized by
      purpura, arthritis, abdominal pain, and hematuria. It is the most common form of
      vasculitis affecting children. The skin manifestations typically present as
      palpable purpura over the buttock and the lower extremities, but bullous lesions
      are particularly rare in children. We report a case of HSP presented as painful
      bullae on both lower limbs.

PMID- 17542895
TI  - Dermatitis artefacta in a 12-year-old girl mimicking cutaneous T-cell lymphoma.
AB  - Dermatitis artefacta or factitious disease may be unrecognized in children. We
      present a 12-year-old girl who had an unusual facial lesion on the chin, which
      was self-inflicted but histologically mimicked cutaneous T-cell lymphoma. Our
      report emphasizes both the potential diagnostic pitfalls and the importance of
      clinicopathologic correlation.

PMID- 17542896
TI  - Visceral involvement in stiff skin syndrome.

PMID- 17542897
TI  - Keratoacanthoma of the lower lip complicating discoid lupus erythematosus in a 14
      year-old boy.

PMID- 17542898
TI  - A rare cause of preseptal cellulitis: anthrax.
AB  - Infection of the eyelids confined to the preseptal space is relatively common but
      potentially serious. We report a child with cutaneous anthrax to remind that the
      interesting contagious cause be included in the differential diagnosis of the
      preseptal cellulitis.

PMID- 17542899
TI  - Childhood nail psoriasis: a useful treatment with tazarotene 0.05%.
AB  - Nail psoriasis occurs in 7% to 40% of children, with a similar pattern of
      clinical presentation to that of adults. In 0.6% to 2.3% of the patients nail
      changes appear as the only sign of the disease, preceding other skin and
      articular involvement. No pediatric clinical trials are available yet, but
      considering the successful use of tazarotene for nail dystrophy therapy in
      adults, we chose this drug to treat a child.

PMID- 17542900
TI  - Erythema multiforme due to diphtheria-pertussis-tetanus vaccine.

PMID- 17542901
TI  - Molluscum contagiosum.

PMID- 17542902
TI  - Plaque type psoriasiform eruption following Kawasaki disease.

PMID- 17542903
TI  - Infantile chondrodermatitis nodularis.

PMID- 17542904
TI  - Hypertrophic infantile pedal papules.

PMID- 17542905
TI  - Sebaceous hyperplasia of the scrotum in an adolescent boy.

PMID- 17542906
TI  - Clouston syndrome associated with severe congenital pseudo-ainhum.

PMID- 17542907
TI  - Granular parakeratosis.

PMID- 17542908
TI  - Beware of mosquitoes: the first instance of a mosquito bite detected by
      fluorodeoxyglucose positron emission tomography.

PMID- 17542909
TI  - Congenital apocrine hamartoma.

PMID- 17542911
TI  - A novel ATP-binding cassette transporter from Leishmania is involved in transport
      of phosphatidylcholine analogues and resistance to alkyl-phospholipids.
AB  - ATP-binding cassette (ABC) transporters represent an important family of membrane
      proteins involved in drug resistance and other biological activities. The present
      work reports the characterization of the first ABC subfamily G (ABCG)-like
      transporter, LiABCG4, in the protozoan parasite Leishmania. LiABCG4 localized
      mainly to the parasite plasma membrane. Overexpression of this half-transporter
      reduced the accumulation of phosphatidylcholine analogues and conferred
      resistance to alkyl-phospholipids. Likewise, when expressed in Saccharomyces
      cerevisiae, the protein localized to the yeast plasma membrane and conferred
      resistance to alkyl-phospholipids. Post-Golgi secretory vesicles isolated from a
      LiABCG4-overexpressing yeast mutant contained the leishmanial ABC transporter and
      exhibited ATP-dependent, vanadate-sensitive transport of phosphatidylcholine
      analogues from the cytosolic to the lumenal leaflet of the vesicle membrane.
      Cross-linking showed dimerization of LiABCG4. These results suggest that LiABCG4
      is involved in the active transport of phosphatidylcholine and resistance to
      alkyl-phospholipids in Leishmania.

PMID- 17542912
TI  - A functionally divergent hydrogenosomal peptidase with protomitochondrial
      ancestry.
AB  - Matrix proteins of mitochondria, hydrogenosomes and mitosomes are typically
      targeted and translocated into their respective organelles using N-terminal
      presequences that are subsequently cleaved by a peptidase. Here we characterize a
      approximately 47 kDa metallopeptidase, from the hydrogenosome-bearing,
      unicellular eukaryote Trichomonas vaginalis, that contains the active site motif
      (HXXEHX(76)E) characteristic of the beta subunit of the mitochondrial processing
      peptidase (MPP) and localizes to hydrogenosomes. The purified recombinant
      protein, named hydrogenosomal processing peptidase (HPP), is capable of cleaving
      a hydrogenosomal presequence in vitro, in contrast to MPP which requires both an
      alpha and beta subunit for activity. T. vaginalis HPP forms an approximately 100
      kDa homodimer in vitro and also exists in an approximately 100 kDa complex in
      vivo. Our phylogenetic analyses support a common origin for HPP and betaMPP and
      demonstrate that gene duplication gave rise to alphaMPP and betaMPP before the
      divergence of T. vaginalis and mitochondria-bearing lineages. These data,
      together with published analyses of MPPs and putative mitosomal processing
      peptidases, lead us to propose that the length of targeting presequences and the
      subunit composition of organellar processing peptidases evolved in concert.
      Specifically, longer mitochondrial presequences may have evolved to require an
      alpha/beta heterodimer for accurate cleavage, while shorter hydrogenosomal and
      mitosomal presequences did not.

PMID- 17542913
TI  - Characterization of a TFIIH homologue from Trypanosoma brucei.
AB  - Trypanosomes are protozoans showing unique transcription characteristics. We
      describe in Trypanosoma brucei a complex homologous to TFIIH, a multisubunit
      transcription factor involved in the control of transcription by RNA Pol I and
      RNA Pol II, but also in DNA repair and cell cycle control. Bioinformatics
      analyses allowed the detection of five genes encoding four putative core TFIIH
      subunits (TbXPD, TbXPB, Tbp44, Tbp52), including a novel XPB variant, TbXPBz. In
      all cases sequences known to be important for TFIIH functions were conserved. We
      performed a molecular analysis of this core complex, focusing on the two subunits
      endowed with a known enzymatic (helicase) activity, XPD and XPB. The involvement
      of these T. brucei proteins in a bona fide TFIIH core complex was supported by
      (i) colocalization by immunofluorescence in the nucleus, (ii) direct physical
      interaction of TbXPD and its interacting regulatory subunit Tbp44 as determined
      by double-hybrid assay and tandem affinity purification of the core TFIIH, (iii)
      involvement of the core proteins in a high molecular weight complex and (iv)
      occurrence of transcription, cell cycle and DNA repair phenotypes upon either
      RNAi knock-down or overexpression of essential subunits.

PMID- 17542914
TI  - The regulation of zinc homeostasis by the ZafA transcriptional activator is
      essential for Aspergillus fumigatus virulence.
AB  - We have previously shown that Aspergillus fumigatus is able to grow in zinc
      limiting media and that this ability is regulated at transcriptional level by
      both the availability of zinc and pH. When A. fumigatus grows as a pathogen, it
      must necessarily obtain zinc from the zinc-limiting environment provided by host
      tissue. Accordingly, the regulation of zinc homeostasis by some zinc-responsive
      transcriptional regulator in A. fumigatus must be essential for fungal growth
      within tissues of an immunocompromised host and, in turn, for pathogenicity. Here
      we provide evidence of the role of the zafA gene in regulating zinc homeostasis
      and its relevance in the virulence of A. fumigatus. Thus, we observed that (i)
      zafA can functionally replace the ZAP1 gene from Saccharomyces cerevisiae that
      encodes the zinc-responsive transcriptional activator Zap1 protein; (ii) the
      expression of zafA itself is induced in zinc-limiting media and repressed by
      zinc; (iii) deletion of zafA impairs the germination and growth capacity of A.
      fumigatus in zinc-limiting media; and (iv) the deletion of zafA abrogates A.
      fumigatus virulence in a murine model of invasive aspergillosis. In light of
      these observations, we concluded that ZafA is a zinc-responsive transcriptional
      activator that represents an essential attribute for A. fumigatus pathogenicity.
      Consequently, ZafA may constitute a new target for the development of
      chemotherapeutic agents against Aspergillus, because no zafA orthologues have
      been found in mammals.

PMID- 17542915
TI  - Oscillating focus of SopA associated with filamentous structure guides
      partitioning of F plasmid.
AB  - The F plasmid is actively partitioned to daughter cells by the sopABC gene. To
      elucidate the partitioning mechanisms, we simultaneously analysed movements of
      the plasmid and the SopA ATPase in single living cells. SopA, which is a putative
      motor protein assembled densely near nucleoid borders and formed a single
      discrete focus associated with less dense filamentous distribution along the long
      axis of the cell. The dense SopA focus oscillates between cell poles. The
      direction of the plasmid motion switches as the SopA focus switches its position.
      The velocity of the plasmid motion stays constant while it oscillates moving
      towards the SopA focus. The low density filamentous distribution of SopA
      persisted throughout the SopA oscillation. The focus associated with filamentous
      distribution of SopA was also observed in a cell without nucleoid. The SopA
      filament may guide the movement of the plasmid as a railway track and lead it to
      cell quarters.

PMID- 17542916
TI  - Identification and type III-dependent secretion of the Yersinia pestis
      insecticidal-like proteins.
AB  - Plague, or the Black Death, is a zoonotic disease that is spread from mammal to
      mammal by fleas. This mode of transmission demands that the causative agent of
      this disease, Yersinia pestis, is able to survive and multiply in both mammals
      and insects. In recent years the complete genome sequence of a number of Y.
      pestis strains have been determined. This sequence information indicates that Y.
      pestis contains a cluster of genes with homology to insecticidal toxin encoding
      genes of the insect pathogen Photorhabdus luminescens. Here we demonstrate that
      Y. pestis KIM strains produced the encoded proteins. Production of the locus
      encoded proteins was dependent on a gene (yitR) encoding a member of the LysR
      family of transcriptional activators. Evidence suggests the proteins are type III
      secretion substrates. N terminal amino acids (100 to 367) of each protein fused
      to an epitope tag were secreted by the virulence plasmid type III secretion type.
      A fusion protein comprised of the N-terminus of YipB and the enzymatic active
      component of Bordetella pertussis adenylate cyclase (Cya) was translocated into
      both mammalian and insect cells. In conclusion, a new class of Y. pestis type III
      secreted and translocated proteins has been identified. We hypothesize that these
      proteins function to promote transmission of and infection by Y. pestis.

PMID- 17542917
TI  - Molecular genetic analysis of purine nucleobase transport in Leishmania major.
AB  - Leishmania major and all other parasitic protozoa are unable to synthesize
      purines de novo and are therefore reliant upon uptake of preformed purines from
      their hosts via nucleobase and nucleoside transporters. L. major expresses two
      nucleobase permeases, NT3 that is a high affinity transporter for purine
      nucleobases and NT4 that is a low affinity transporter for adenine. nt3((-/-))
      null mutant promastigotes were unable to replicate in medium containing 10 microM
      hypoxanthine, guanine, or xanthine and replicated slowly in 10 microM adenine due
      to residual low affinity uptake of that purine. The NT3 transporter mediated the
      uptake of the anti-leishmanial drug allopurinol, and the nt3((-/-)) mutants were
      resistant to killing by this drug. Expression of the NT3 permease was profoundly
      downregulated at the protein but not the mRNA level in stationary phase compared
      with logarithmic phase promastigotes. The nt4((-/-)) null mutant was
      quantitatively impaired in survival within murine bone marrow-derived
      macrophages. Extensive efforts to generate an nt3((-/-))/nt4((-/-)) dual null
      mutant were not successful, suggesting that one of the two nucleobase permeases
      must be retained for robust growth of the parasite. The phenotypes of these null
      mutants underscore the importance of purine nucleobase transporters in the
      Leishmania life cycle and pharmacology.

PMID- 17542918
TI  - Loss of the controlled localization of growth stage-specific cell-wall synthesis
      pleiotropically affects developmental gene expression in an ssgA mutant of
      Streptomyces coelicolor.
AB  - Members of the family of SsgA-like proteins (SALPs) are found exclusively in
      sporulating actinomycetes, and SsgA itself activates sporulation-specific cell
      division. We previously showed that SALPs play a chaperonin-like role in
      supporting the function of enzymes involved in peptidoglycan maintenance (PBPs
      and autolysins). Here we show that SsgA localizes dynamically during development,
      and most likely marks the sites where changes in local cell-wall morphogenesis
      are required, in particular septum formation and germination. In sporogenic
      aerial hyphae, SsgA initially localizes as strong foci to the growing tips,
      followed by distribution as closely spaced foci in a pattern similar to an early
      stage of FtsZ assembly. Spore septa formed in these hyphae colocalize with single
      SsgA-GFP foci, and when the maturing spores are separated, these foci are
      distributed symmetrically, resulting in two foci per mature spore. Evidence is
      provided that SsgA also controls the correct localization of germination sites.
      Transcriptome analysis revealed that expression of around 300 genes was
      significantly altered in mutants in ssgA and its regulatory gene ssgR. The list
      includes surprisingly many known developmental genes, most of which were
      upregulated, highlighting SsgA as a key player in the control of Streptomyces
      development.

PMID- 17542919
TI  - The small RNA RyhB activates the translation of shiA mRNA encoding a permease of
      shikimate, a compound involved in siderophore synthesis.
AB  - RyhB is a small RNA (sRNA) that downregulates about 20 genes involved in iron
      metabolism. It is expressed under low iron conditions and pairs with specific
      mRNAs to trigger their rapid degradation by the RNA degradosome. In contrast to
      this, another study has suggested that RyhB also activates several genes by
      increasing their mRNA level. Among these activated genes is shiA, which encodes a
      permease of shikimate, an aromatic compound participating in the biosynthesis of
      siderophores. Here, we demonstrate in vivo and in vitro that RyhB directly pairs
      at the 5'-untranslated region (5'-UTR) of the shiA mRNA to disrupt an intrinsic
      inhibitory structure that sequesters the ribosome-binding site (Shine-Dalgarno)
      and the first translation codon. This is the first demonstration of direct gene
      activation by RyhB, which has been exclusively described in degradation of mRNAs.
      Our physiological results indicate that the transported compound of the ShiA
      permease, shikimate, is important under conditions of RyhB expression, that is,
      iron starvation. This is demonstrated by growth assays in which shikimate or the
      siderophore enterochelin correct the growth defect observed for a ryhB mutant in
      iron-limited media.

PMID- 17542920
TI  - Clostridium difficile toxin expression is inhibited by the novel regulator TcdC.
AB  - Clostridium difficile, an emerging nosocomial pathogen of increasing clinical
      significance, produces two large protein toxins that are responsible for the
      cellular damage associated with the disease. The precise mechanisms by which
      toxin synthesis is regulated in response to environmental change have yet to be
      discovered. The toxin genes (tcdA and tcdB) are located in a pathogenicity locus
      (PaLoc), along with tcdR and tcdC. TcdR is an alternative RNA polymerase sigma
      factor that directly activates toxin gene expression, while the inverse
      relationship between expression of tcdR, tcdA and tcdB genes on the one hand and
      tcdC on the other has led to the suggestion that TcdC somehow interferes with
      toxin gene expression. This idea is further supported by the finding that many
      recent C. difficile epidemic strains in which toxin production is increased carry
      a common tcdC deletion mutation. In this report we demonstrate that TcdC
      negatively regulates toxin synthesis both in vivo and in vitro. TcdC destabilizes
      the TcdR-containing holoenzyme before open complex formation, apparently by
      interaction with TcdR or TcdR-containing RNA polymerase holoenzyme or both. In
      addition, we show that the hypertoxigenicity phenotype of C. difficile epidemic
      strains is not due to their common 18 bp in-frame deletion in tcdC.

PMID- 17542921
TI  - An altered FtsA can compensate for the loss of essential cell division protein
      FtsN in Escherichia coli.
AB  - FtsN is the last known essential protein component to be recruited to the
      Escherichia coli divisome, and has several special properties. Here we report the
      isolation of suppressor mutants of ftsA that allow viability in the absence of
      ftsN. Cells producing the FtsA suppressors exhibited a mild cell division
      deficiency in the absence of FtsN, and no obvious phenotype in its presence.
      Remarkably, these altered FtsA proteins also could partially suppress a deletion
      of ftsK or zipA, were less toxic than wild-type FtsA when in excess, and
      conferred resistance to excess MinC, indicating that they share some properties
      with the previously isolated FtsA* suppressor mutant, and bypass the need for
      ftsN by increasing the integrity of the Z ring. TolA, which normally requires
      FtsN for its recruitment to the divisome, localized proficiently in the
      suppressed ftsN null strain, strongly suggesting that FtsN does not recruit the
      Tol-Pal complex directly. Therefore, despite its classification as a core
      divisome component, FtsN has no unique essential function but instead promotes
      overall Z ring integrity. The results strongly suggest that FtsA is
      conformationally flexible, and this flexibility is a key modulator of divisome
      function at all stages.

PMID- 17542922
TI  - Class I and class II lysyl-tRNA synthetase mutants and the genetic encoding of
      pyrrolysine in Methanosarcina spp.
AB  - Methanosarcina spp. begin methanogenesis from methylamines with
      methyltransferases made via the translation of UAG as pyrrolysine. In vitro
      evidence indicates two possible routes to pyrrolysyl-tRNA(Pyl). PylS ligates
      pyrrolysine to tRNA(Pyl). Alternatively, class I and class II lysyl-tRNA
      synthetases (LysRS1 and LysRS2) together form lysyl-tRNA(Pyl), a potential
      intermediate to pyrrolysyl-tRNA(Pyl). The unusual possession of both LysRS1 and
      LysRS2 by Methanosarcina spp. may also reflect differences in catalytic
      properties. Here we assessed the in vivo relevance of these hypotheses. The lysK
      and mtmB transcripts, encoding LysRS1 and monomethylamine methyltransferase, were
      detectable in Methanosarcina barkeri during early log growth on trimethylamine,
      but not methanol. In contrast, lysS transcript encoding LysRS2 was detectable
      during log phase with either substrate. Methanosarcina acetivorans strains
      bearing deletions of lysK or lysS grew normally on methanol and methylamines with
      wild-type levels of monomethylamine methyltransferase and aminoacyl-tRNA(Pyl).
      The lysK and lysS genes could not replace pylS in a recombinant system employing
      tRNA(Pyl) for UAG suppression. The results support an association of LysRS1 with
      growth on methylamine, but not an essential role for LysRS1/LysRS2 in the genetic
      encoding of pyrrolysine. However, decreased lysyl-tRNA(Lys) in the lysS mutant
      provides a possible rationale for stable transfer of the bacterial lysS gene to
      methanoarchaea.

PMID- 17542923
TI  - Scl1-dependent internalization of group A Streptococcus via direct interactions
      with the alpha2beta(1) integrin enhances pathogen survival and re-emergence.
AB  - The molecular pathogenesis of infections caused by group A Streptococcus (GAS) is
      not fully understood. We recently reported that a recombinant protein derived
      from the collagen-like surface protein, Scl1, bound to the human collagen
      receptor, integrin alpha(2)beta(1). Here, we investigate whether the same Scl1
      variant expressed by GAS cells interacts with the integrin alpha2beta(1) and
      affects the biological outcome of host-pathogen interactions. We demonstrate that
      GAS adherence and internalization involve direct interactions between surface
      expressed Scl1 and the alpha2beta(1) integrin, because (i) both adherence and
      internalization of the scl1-inactivated mutant were significantly decreased, and
      were restored by in-trans complementation of Scl1 expression, (ii) GAS
      internalization was reduced by pre-treatment of HEp-2 cells with anti-alpha2
      integrin-subunit antibody and type I collagen, (iii) recombinant alpha2-I domain
      bound the wild-type GAS cells and (iv) internalization of wild-type cells was
      significantly increased in C2C12 cells expressing the alpha2beta(1) integrin as
      the only collagen-binding integrin. Next, we determined that internalized GAS re
      emerges from epithelial cells into the extracellular environment. Taken together,
      our data describe a new molecular mechanism used by GAS involving the direct
      interaction between Scl1 and integrins, which increases the overall capability of
      the pathogen to survive and re-emerge.

PMID- 17542924
TI  - Saccharomyces cerevisiae SSD1 orthologues are essential for host infection by the
      ascomycete plant pathogens Colletotrichum lagenarium and Magnaporthe grisea.
AB  - Fungal plant pathogens have evolved diverse strategies to overcome the
      multilayered plant defence responses that confront them upon host invasion. Here
      we show that pathogenicity of the cucumber anthracnose fungus, Colletotrichum
      lagenarium, and the rice blast fungus, Magnaporthe grisea, requires a gene
      orthologous to Saccharomyces cerevisiae SSD1, a regulator of cell wall assembly.
      Screening for C. lagenarium insertional mutants deficient in pathogenicity led to
      the identification of ClaSSD1. Following targeted gene replacement, appressoria
      of classd1 mutants retained the potential for penetration but were unable to
      penetrate into host epidermal cells. Transmission electron microscopy suggested
      that appressorial penetration by classd1 mutants was restricted by plant cell
      wall-associated defence responses, which were observed less frequently with the
      wild-type strain. Interestingly, on non-host onion epidermis classd1 mutants
      induced papilla formation faster and more abundantly than the wild type.
      Similarly, colonization of rice leaves by M. grisea was severely reduced after
      deletion of the orthologous MgSSD1 gene and attempted infection by the mutants
      was accompanied by the accumulation of reactive oxygen species within the host
      cell. These results suggest that appropriate assembly of the fungal cell wall as
      regulated by SSD1 allows these pathogens to establish infection by avoiding the
      induction of host defence responses.

PMID- 17542925
TI  - YaeT-independent multimerization and outer membrane association of secretin PulD.
AB  - Previous studies demonstrated that targeting of the dodecameric secretin PulD to
      the Escherichia coli outer membrane is strictly dependent on the chaperone-like
      pilotin PulS. Here, we report that PulD multimerization and membrane association
      in strains producing PulS were unaffected when the levels of the essential outer
      membrane assembly factor YaeT(Omp85) were reduced by controlled expression of a
      paraBAD-yaeT transcriptional fusion. This behaviour contrasted markedly to that
      of the trimeric porin LamB, which remained monomeric under these conditions.
      Furthermore, resistance to extraction by the detergent Sarkosyl and by urea, and
      susceptibility to trypsin digestion all suggested that PulD localized to the
      outer membrane in YaeT-depleted cells. We conclude that, unlike classical beta
      barrel outer membrane proteins such as LamB, multimerization of PulD is largely
      YaeT-independent.

PMID- 17542926
TI  - The critical role of the linear plasmid lp36 in the infectious cycle of Borrelia
      burgdorferi.
AB  - Borrelia burgdorferi, the aetiological agent of Lyme disease, follows a life
      cycle that involves passage between the tick vector and the mammalian host. To
      investigate the role of the 36 kb linear plasmid, lp36 (also designated the B.
      burgdorferi K plasmid), in the infectious cycle of B. burgdorferi, we examined a
      clone lacking this plasmid, but containing all other plasmids known to be
      required for infectivity. Our results indicated that lp36 was not required for
      spirochete survival in the tick, but the clone lacking lp36 demonstrated low
      infectivity in the mammal. Restoration of lp36 to the mutant strain confirmed
      that the infectivity defect was due to loss of lp36. Moreover, spirochetes
      lacking lp36 exhibited a nearly 4-log increase in ID(50) relative to the isogenic
      lp36(+) clone. The infectivity defect of lp36-minus spirochetes was localized, in
      part, to loss of the bbk17 (adeC) gene, which encodes an adenine deaminase. This
      work establishes a vital role for lp36 in the infectious cycle of B. burgdorferi
      and identifies the bbk17 gene as a component of this plasmid that contributes to
      mammalian infectivity.

PMID- 17542927
TI  - The ArcA regulon and oxidative stress resistance in Haemophilus influenzae.
AB  - Haemophilus influenzae transits between niches within the human host that are
      predicted to differ in oxygen levels. The ArcAB two-component signal transduction
      system controls gene expression in response to respiratory conditions of growth
      and has been implicated in bacterial pathogenesis, yet the mechanism is not
      understood. We undertook a genome-scale study to identify genes of the H.
      influenzae ArcA regulon. Deletion of arcA resulted in increased anaerobic
      expression of genes of the respiratory chain and of H. influenzae's partial
      tricarboxylic acid cycle, and decreased anaerobic expression levels of genes of
      polyamine metabolism, and iron sequestration. Deletion of arcA also conferred a
      susceptibility to transient exposure to hydrogen peroxide that was greater
      following anaerobic growth than after aerobic growth. Array data revealed that
      the dps gene, not previously assigned to the ArcA modulon in bacteria, exhibited
      decreased expression in the arcA mutant. Deletion of dps resulted in hydrogen
      peroxide sensitivity and complementation restored resistance, providing insight
      into the previously uncharacterized mechanism of arcA-mediated H(2)O(2)
      resistance. The results indicate a role for H. influenzae arcA and dps in pre
      emptive defence against transitions from growth in low oxygen environments to
      aerobic exposure to hydrogen peroxide, an antibacterial oxidant produced by
      phagocytes during infection.

PMID- 17542928
TI  - Identification of a new OmpA-like protein in Neisseria gonorrhoeae involved in
      the binding to human epithelial cells and in vivo colonization.
AB  - Outer membrane protein As (OmpAs) are highly conserved proteins within the
      Enterobacteriaceae family. OmpA contributes to the maintenance of structural
      membrane integrity and invasion into mammalian cells. In Escherichia coli K1 OmpA
      also contributes to serum resistance and is involved in the virulence of the
      bacterium. Here we describe the identification of an OmpA-like protein in
      Neisseria gonorrhoeae (Ng-OmpA). We show that the gonococcal OmpA-like protein,
      similarly to E. coli OmpA, plays a significant role in the adhesion and invasion
      into human cervical carcinoma and endometrial cells and is required for entry
      into macrophages and intracellular survival. Furthermore, the isogenic knockout
      ompA mutant demonstrates reduced recovery in a mouse model of infection when
      compared with the wild-type strain, suggesting that Ng-OmpA plays an important
      role in the in vivo colonization. All together, these data suggest that the newly
      identified surface exposed protein Ng-OmpA represents a novel virulence factor of
      gonococcus.

PMID- 17542929
TI  - FliK regulates flagellar hook length as an internal ruler.
AB  - The mechanism of length control of the flagellar hook is under debate between two
      theories. One claims that the FliK directly measures the hook length as a
      molecular ruler, while the other claims that the cytoplasmic substructure
      measures the amount of hook subunits to determine the hook length. Both agree
      that the FliK C-terminal domain catalyses the substrate-specificity switch to
      terminate hook elongation. In this study, we systematically created fliK mutants
      with deletions and insertions at various sites within the FliK N-terminal domain
      and analysed their effects on the final hook length. Insertions of peptide
      fragments from the Yersinia YscP into FliK gave rise to hooks with defined
      lengths, which was proportional to the molecular size of the FliK-YscP chimeras.
      Among fliK deletion mutants, only those with small truncations in three specific
      sites of FliK produced hooks of a defined, shortened length. For the majority of
      deletion mutants, FliK was secreted, but hook length was not controlled. On the
      other hand, for some deletion mutants FliK was not secreted, but the hook length
      was controlled, indicating that FliK secretion is not necessary for hook-length
      control. We conclude that FliK regulates hook length as an internal molecular
      ruler.

PMID- 17542933
TI  - The impact of an alien plant on a native plant-pollinator network: an
      experimental approach.
AB  - Studies of pairwise interactions have shown that an alien plant can affect the
      pollination of a native plant, this effect being mediated by shared pollinators.
      Here we use a manipulative field experiment, to investigate the impact of the
      alien plant Impatiens glandulifera on an entire community of coflowering native
      plants. Visitation and pollen transport networks were constructed to compare
      replicated I. glandulifera invaded and I. glandulifera removal plots. Invaded
      plots had significantly higher visitor species richness, visitor abundance and
      flower visitation. However, the pollen transport networks were dominated by alien
      pollen grains in the invaded plots and consequently higher visitation may not
      translate in facilitation for pollination. The more generalized insects were more
      likely to visit the alien plant, and Hymenoptera and Hemiptera were more likely
      to visit the alien than Coleoptera. Our data indicate that generalized native
      pollinators can provide a pathway of integration for alien plants into native
      visitation systems.

PMID- 17542934
TI  - Data cloning: easy maximum likelihood estimation for complex ecological models
      using Bayesian Markov chain Monte Carlo methods.
AB  - We introduce a new statistical computing method, called data cloning, to
      calculate maximum likelihood estimates and their standard errors for complex
      ecological models. Although the method uses the Bayesian framework and exploits
      the computational simplicity of the Markov chain Monte Carlo (MCMC) algorithms,
      it provides valid frequentist inferences such as the maximum likelihood estimates
      and their standard errors. The inferences are completely invariant to the choice
      of the prior distributions and therefore avoid the inherent subjectivity of the
      Bayesian approach. The data cloning method is easily implemented using standard
      MCMC software. Data cloning is particularly useful for analysing ecological
      situations in which hierarchical statistical models, such as state-space models
      and mixed effects models, are appropriate. We illustrate the method by fitting
      two nonlinear population dynamics models to data in the presence of process and
      observation noise.

PMID- 17542935
TI  - Synchrony's double edge: transient dynamics and the Allee effect in stage
      structured populations.
AB  - In populations subject to positive density dependence, individuals can increase
      their fitness by synchronizing the timing of key life history events. However,
      phenological synchrony represents a perturbation from a population's stable stage
      structure and the ensuing transient dynamics create troughs of low abundance that
      can promote extinction. Using an ecophysiological model of a mass-attacking pest
      insect, we show that the effect of synchrony on local population persistence
      depends on population size and adult lifespan. Results are consistent with a
      strong empirical pattern of increased extinction risk with decreasing initial
      population size. Mortality factors such as predation on adults can also affect
      transient dynamics. Throughout the species range, the seasonal niche for
      persistence increases with the asynchrony of oviposition. Exposure to the Allee
      effect after establishment may be most likely at northern range limits, where
      cold winters tend to synchronize spring colonization, suggesting a role for
      transient dynamics in the determination of species distributions.

PMID- 17542936
TI  - The effects of immigration and environmental variability on the persistence of an
      inferior competitor.
AB  - We tested the hypothesis that temporally autocorrelated variation should increase
      the abundance of an inferior competitor sustained by immigration. Temporally
      autocorrelated variability can increase abundance of the inferior species through
      effects on demography, the strength of competition, and the mean and variance in
      the abundance of competing species. We allowed the competitive inferior to
      immigrate into habitats with constant, variable, or temporally autocorrelated
      temperature regimes. In the absence of immigration, competitive exclusion
      occurred, in both constant and variable environments. Immigration permitted
      persistence of the inferior species, and increased immigration rates led to
      increased abundance. Temporally autocorrelated variability enhanced this effect
      of immigration. This 'inflationary' effect suggests that the interplay of
      immigration and environmental variability can jointly influence the outcome of
      competitive interactions. Our results suggest that an increase in temporal
      autocorrelation of environmental variability will cause regional processes to
      increasingly influence local interactions.

PMID- 17542937
TI  - Species-area relationships from a spatially explicit neutral model in an infinite
      landscape.
AB  - We use recently developed technical methods to study species-area relationships
      from a spatially explicit extension of Hubbell's neutral model on an infinite
      landscape. Our model includes variable dispersal distances and exhibits
      qualitatively different behaviour from the cases of nearest-neighbour dispersal
      and finite periodic landscapes that have previously been studied. We show that
      different dispersal distances and even different dispersal kernels produce
      identical species-area curves up to rescaling of the two axes. This scaling
      property provides a straightforward method for fitting the model to empirical
      data. The species-area curves display all three phases observed empirically and
      enable the exponent describing the power law relationship for species-area curves
      to be identified as the gradient at the central phase. This exponent can take all
      values between 0 and 1 and is given by a simple function of the speciation rate,
      independent of all other model variables.

PMID- 17542938
TI  - Environmental and plant community determinants of species loss following nitrogen
      enrichment.
AB  - Global energy use and food production have increased nitrogen inputs to
      ecosystems worldwide, impacting plant community diversity, composition, and
      function. Previous studies show considerable variation across terrestrial
      herbaceous ecosystems in the magnitude of species loss following nitrogen (N)
      enrichment. What controls this variation remains unknown. We present results from
      23 N-addition experiments across North America, representing a range of climatic,
      soil and plant community properties, to determine conditions that lead to greater
      diversity decline. Species loss in these communities ranged from 0 to 65% of
      control richness. Using hierarchical structural equation modelling, we found
      greater species loss in communities with a lower soil cation exchange capacity,
      colder regional temperature, and larger production increase following N addition,
      independent of initial species richness, plant productivity, and the relative
      abundance of most plant functional groups. Our results indicate sensitivity to N
      addition is co-determined by environmental conditions and production
      responsiveness, which overwhelm the effects of initial community structure and
      composition.

PMID- 17542939
TI  - A neutral sampling formula for multiple samples and an 'exact' test of
      neutrality.
AB  - As the utility of the neutral theory of biodiversity is increasingly being
      recognized, there is also an increasing need for proper tools to evaluate the
      relative importance of neutral processes (dispersal limitation and
      stochasticity). One of the key features of neutral theory is its close link to
      data: sampling formulas, giving the probability of a data set conditional on a
      set of model parameters, have been developed for parameter estimation and model
      comparison. However, only single local samples can be handled with the currently
      available sampling formulas, whereas data are often available for many small
      spatially separated plots. Here, I present a sampling formula for multiple,
      spatially separated samples from the same metacommunity, which is a
      generalization of earlier sampling formulas. I also provide an algorithm to
      generate data sets with the model and I introduce a general test of neutrality
      that does not require an alternative model; this test compares the probability of
      the observed data (calculated using the new sampling formula) with the
      probability of model-generated data sets. I illustrate this with tree abundance
      data from three large Panamanian neotropical forest plots. When the test is
      performed with model parameters estimated from the three plots, the model cannot
      be rejected; however, when parameter estimates previously reported for BCI are
      used, the model is strongly rejected. This suggests that neutrality cannot
      explain the structure of the three Panamanian tree communities on the local (BCI)
      and regional (Panama Canal Zone) scale simultaneously. One should be aware,
      however, that aspects of the model other than neutrality may be responsible for
      its failure. I argue that the spatially implicit character of the model is a
      potential candidate.

PMID- 17542940
TI  - Global negative vegetation feedback to climate warming responses of leaf litter
      decomposition rates in cold biomes.
AB  - Whether climate change will turn cold biomes from large long-term carbon sinks
      into sources is hotly debated because of the great potential for ecosystem
      mediated feedbacks to global climate. Critical are the direction, magnitude and
      generality of climate responses of plant litter decomposition. Here, we present
      the first quantitative analysis of the major climate-change-related drivers of
      litter decomposition rates in cold northern biomes worldwide. Leaf litters
      collected from the predominant species in 33 global change manipulation
      experiments in circum-arctic-alpine ecosystems were incubated simultaneously in
      two contrasting arctic life zones. We demonstrate that longer-term, large-scale
      changes to leaf litter decomposition will be driven primarily by both direct
      warming effects and concomitant shifts in plant growth form composition, with a
      much smaller role for changes in litter quality within species. Specifically, the
      ongoing warming-induced expansion of shrubs with recalcitrant leaf litter across
      cold biomes would constitute a negative feedback to global warming. Depending on
      the strength of other (previously reported) positive feedbacks of shrub expansion
      on soil carbon turnover, this may partly counteract direct warming enhancement of
      litter decomposition.

PMID- 17542941
TI  - Development of a diverse epiphyte community in response to phosphorus
      fertilization.
AB  - The role of terrestrial soil nutrient supply in determining the composition and
      productivity of epiphyte communities has been little investigated. In a montane
      Hawaiian rainforest, we documented dramatic increases in the abundance and
      species richness of canopy epiphytes in a forest that had been fertilized
      annually with phosphorus (P) for 15 years; there was no response in forest that
      had been fertilized with nitrogen (N) or other nutrients. The response of N
      fixing lichens to P fertilization was particularly strong, although mosses and
      non-N-fixing lichens also increased in abundance and diversity. We show that
      enhancement of canopy P availability is the most likely factor driving the bloom
      in epiphytes. These results provide strong evidence that terrestrial soil
      fertility may structure epiphyte communities, and in particular that the
      abundance of N-fixing lichens--a functionally important epiphyte group--may be
      particularly sensitive to ecosystem P availability.

PMID- 17542942
TI  - Setting the absolute tempo of biodiversity dynamics.
AB  - Neutral biodiversity theory has the potential to contribute to our understanding
      of how macroevolutionary dynamics influence contemporary biodiversity, but there
      are issues regarding its dynamical predictions that must first be resolved. Here
      we address these issues by extending the theory in two ways using a novel
      analytical approach: (1) we set the absolute tempo of biodiversity dynamics by
      explicitly incorporating population-level stochasticity in abundance; (2) we
      allow new species to arise with more than one individual. Setting the absolute
      tempo yields quantitative predictions on biodiversity dynamics that can be tested
      using contemporary and fossil data. Allowing incipient-species abundances greater
      than one individual yields predictions on how these dynamics, and the form of the
      species-abundance distribution, are affected by multiple speciation modes. We
      apply this new model to contemporary and fossil data that encompass 30 Myr of
      macroevolution for planktonic foraminifera. By synthesizing the model with these
      empirical data, we present evidence that dynamical issues with neutral
      biodiversity theory may be resolved by incorporating the effects of environmental
      stochasticity and incipient-species abundance on biodiversity dynamics.

PMID- 17542943
TI  - Immediate error correction process following sleep deprivation.
AB  - Previous studies have suggested that one night of sleep deprivation decreases
      frontal lobe metabolic activity, particularly in the anterior cingulated cortex
      (ACC), resulting in decreased performance in various executive function tasks.
      This study thus attempted to address whether sleep deprivation impaired the
      executive function of error detection and error correction. Sixteen young healthy
      college students (seven women, nine men, with ages ranging from 18 to 23 years)
      participated in this study. Participants performed a modified letter flanker task
      and were instructed to make immediate error corrections on detecting performance
      errors. Event-related potentials (ERPs) during the flanker task were obtained
      using a within-subject, repeated-measure design. The error negativity or error
      related negativity (Ne/ERN) and the error positivity (Pe) seen immediately after
      errors were analyzed. The results show that the amplitude of the Ne/ERN was
      reduced significantly following sleep deprivation. Reduction also occurred for
      error trials with subsequent correction, indicating that sleep deprivation
      influenced error correction ability. This study further demonstrated that the
      impairment in immediate error correction following sleep deprivation was confined
      to specific stimulus types, with both Ne/ERN and behavioral correction rates
      being reduced only for trials in which flanker stimuli were incongruent with the
      target stimulus, while the response to the target was compatible with that of the
      flanker stimuli following sleep deprivation. The results thus warrant future
      systematic investigation of the interaction between stimulus type and error
      correction following sleep deprivation.

PMID- 17542944
TI  - Robust circadian rhythm in heart rate and its variability: influence of exogenous
      melatonin and photoperiod.
AB  - Heart rate (HR) and heart rate variability (HRV) undergo marked fluctuations over
      the 24-h day. Although controversial, this 24-h rhythm is thought to be driven by
      the sleep-wake/rest-activity cycle as well as by endogenous circadian
      rhythmicity. We quantified the endogenous circadian rhythm of HR and HRV and
      investigated whether this rhythm can be shifted by repeated melatonin
      administration while exposed to an altered photoperiod. Eight healthy males (age
      24.4 +/- 4.4 years) participated in a double-blind cross-over design study. In
      both conditions, volunteers were scheduled to 16 h-8 h rest : wake and dark :
      light cycles for nine consecutive days preceded and followed by 29-h constant
      routines (CR) for assessment of endogenous circadian rhythmicity. Melatonin (1.5
      mg) or placebo was administered at the beginning of the extended sleep
      opportunities. For all polysomnographically verified wakefulness periods of the
      CR, we calculated the high- (HF) and low- (LF) frequency bands of the power
      spectrum of the R-R interval, the standard deviation of the normal-to-normal (NN)
      intervals (SDNN) and the square root of the mean-squared difference of successive
      NN intervals (rMSSD). HR and HRV variables revealed robust endogenous circadian
      rhythms with fitted maxima, respectively, in the afternoon (16:36 hours) and in
      the early morning (between 05:00 and 06:59 hours). Melatonin treatment phase
      advanced HR, HF, SDNN and rMSSD, and these shifts were significantly greater than
      after placebo treatment. We conclude that endogenous circadian rhythmicity
      influences autonomic control of HR and that the timing of these endogenous
      rhythms can be altered by extended sleep/rest episodes and associated changes in
      photoperiod as well as by melatonin treatment.

PMID- 17542945
TI  - Heritability of diurnal type: a nationwide study of 8753 adult twin pairs.
AB  - Twin studies suggest a genetic component in diurnal types. In 1981, a
      questionnaire sent to the Older Finnish Twin Cohort yielded responses from 2836
      adult monozygotic (MZ) and 5917 like-sexed dizygotic (DZ) twin pairs with four
      category self-report on diurnal type. We used structural equation modelling to
      estimate genetic and environmental components of variance in morningness and
      eveningness. The model fitting was best when the morningness and the eveningness
      were analysed together. The ADE-model (including additive genetic, dominant
      genetic and non-shared environmental effects) fitted best to the data. ADE-models
      for men and women separately did not differ in a statistically significant manner
      from the combined model, and similarly ADE-models for young and old age groups
      separately did not differ either. The estimate for overall genetic effect (broad
      sense heritability) was 49.7% (95% confidence interval 46.4-52.8), with the
      remainder accounted for by environmental factors not shared by siblings. The
      variance component estimates for the underlying liability to diurnal type were
      11.7% (95% CI 0-23.7) for additive genetic factors, 38.0% (24.7-51.3) for genetic
      factors due to dominance. Genetic effects thus account for about one-half of the
      interindividual variability in diurnal type in adults.

PMID- 17542946
TI  - Sleep habits and circadian preference in Italian children and adolescents.
AB  - Sleep habits and circadian preference (morningness/eveningness, M/E) have been
      extensively analyzed in adolescents and young adults, while few studies were
      conducted on children and early adolescents. Aim of the present study was to
      investigate the developmental changes of circadian preference and to analyze its
      relationship with sleep habits, sleep problems and circadian preference in a
      large sample by means of a school-based survey. One thousand seventy-three
      participants (50.8% boys and 49.2% girls; mean age = 10.6; range = 8-14 years),
      recruited from four schools randomly extracted within the district of Rome,
      completed a modified version of School Sleep Habits Survey developed by Carskadon
      et al. The questionnaire included items about sleep habits during schooldays and
      weekends; a Sleepiness Scale; a Sleep-Wake Problems Behaviour Scale; a
      Morningness/Eveningness scale. The results show a consistent age-related change
      in sleep habits, particularly in the weekends. The difference in sleep duration
      between schooldays and weekends increases linearly with age. No gender difference
      was observed in morningness/eveningness, while a significant linear increase in
      evening preference was found with increasing ages. M/E total scores correlated
      significantly with both self-reported sleep/wake problems and daytime sleepiness
      indicating a higher prevalence of sleep complaints in evening-type subjects.
      Overall, the present results support the existence of consistent age-related
      changes in sleep habits and M/E dimension in the 8- to 14-year age range.

PMID- 17542947
TI  - Trait interindividual differences in the sleep physiology of healthy young
      adults.
AB  - Despite decades of sleep research by means of polysomnography (PSG), systematic
      interindividual differences in PSG-assessed sleep parameters have been scarcely
      investigated. The present study is the first to quantify interindividual
      variability in standard PSG-assessed variables of sleep structure in terms of
      stability and robustness as well as magnitude. Twenty-one carefully screened
      healthy young adults were studied continuously in a strictly controlled
      laboratory environment, where their PSGs were recorded for eight nights
      interspersed with three separate 36 h sleep deprivation periods. All PSG records
      were scored blind to subject and condition, using conventional criteria, and
      delta power in the non-REM sleep EEG was computed for four electrode derivations.
      Interindividual differences in sleep variables were examined for stability and
      robustness, respectively, by comparing results across equivalent nights (e.g.
      baseline nights) and across experimentally differentiated nights (baseline nights
      versus recovery nights following sleep deprivation). Among 18 sleep variables
      analyzed, all except slow-wave sleep (SWS) latency were found to exhibit
      significantly stable and robust--i.e. trait-like--interindividual differences.
      This was quantified by means of intraclass correlation coefficients (ICCs), which
      ranged from 36% to 89% across physiologic variables, and were highest for SWS
      (73%) and delta power in the non-REM sleep EEG (78-89%). The magnitude of the
      trait interindividual differences was considerable, consistently exceeding the
      magnitude of the group-average effect on sleep structure of 36 h total sleep
      deprivation. Notably, for non-REM delta power--a putative marker of sleep
      homeostasis--the interindividual differences were from 9.9 to 12.8 times greater
      than the group-average increase following sleep deprivation relative to baseline.
      Physiologic sleep variables did not vary among subjects in a completely
      independent manner--61.1% of their combined variance clustered in three trait
      dimensions, which appeared to represent sleep duration, sleep intensity, and
      sleep discontinuity. Any independent functional significance of these sleep
      physiologic phenotypes remains to be determined.

PMID- 17542948
TI  - The use of actigraphy for assessment of the development of sleep/wake patterns in
      infants during the first 12 months of life.
AB  - Maturation of sleep/wake patterns is one of the most important physiological
      developments during the first year of life. In this study, we aimed to compare
      the use of actigraphy and parental sleep diaries (SD) for recording the
      development of sleep/wake patterns longitudinally in term infants in their own
      home environments over the first 12 months of life. Twenty healthy term infants
      (7F/13M) were studied for 3 days each month in their own homes over the first 12
      months of life. Sleep/wake patterns were recorded using both SD and actigraphy
      (AW) (AW64, Mini Mitter Co. Inc., Sunriver, OR, USA). The development of sleep
      and wake was analysed over 24 h, during the day (08:00-20:00 hours) and during
      the night (20:00-08:00 hours). A total of 186 studies had complete data sets for
      both analysis methods. Overall, there was no difference between methods of
      measurement for determination of the total percentage of sleep or wake over 24 h,
      or for the total percentage of sleep or wake during the day. However, at night,
      AW scored less time asleep (73.3 +/- 0.9%) and more time awake (26.7 +/- 0.9%)
      compared with the SD (80.7 +/- 1.04% and 19 +/- 1.0%, respectively, P < 0.001).
      Mean percentage sleep during the day decreased from 51% at 1 month to 28% at 12
      months with the 1-month values being significantly higher than all other ages,
      while mean percentage sleep at night was only different between 1 month and 11
      and 12 months. In conclusion actigraphy provides a useful tool for assessing the
      development infant sleep.

PMID- 17542949
TI  - The association between children's sleep disruption and salivary interleukin-6.
AB  - We explored relations between children's sleep and levels of salivary interleukin
      6 (IL-6). Children were healthy boys (n = 28) and girls (n = 36) who ranged in
      age between 8 and 9 years. Through actigraphy, the amount and quality of
      children's sleep was examined objectively in their homes for 1 week. Children
      also rated their Morningness/Eveningness predisposition and subjective
      sleepiness, and parents reported on their children's Sleep Disordered Breathing
      and Sleepiness. Children provided saliva samples before and after a series of
      cognitive/social tasks (an intelligence test, listening to a marital argument,
      and performing a star-tracing task), which were later assayed for IL-6. Children
      with higher salivary IL-6 levels reported increased Eveningness predispositions
      and their parents reported higher levels of Sleep Disordered Breathing.
      Furthermore, lower levels of sleepiness, longer sleep amount, and better quality
      sleep in children were each predictive of increased IL-6 reactivity from pre- to
      post-task conditions. The findings illustrate (for the first time to our
      knowledge) that sleep disruptions in otherwise healthy and normally developing
      children may be associated with individual differences in levels of IL-6 in
      saliva.

PMID- 17542950
TI  - Alcohol-induced sleepwalking or confusional arousal as a defense to criminal
      behavior: a review of scientific evidence, methods and forensic considerations.
AB  - An increasing number of criminal cases have claimed the defendant to be in a
      state of sleepwalking or related disorders induced by high quantities of alcohol.
      Sleepwalkers who commit violent acts, sexual assaults and other criminal acts are
      thought to be in a state of automatism, lacking conscious awareness and criminal
      intent. They may be acquitted in criminal trials. On the other hand, criminal
      acts performed as the result of voluntary alcohol intoxication alone cannot be
      used as a complete defense. The alcohol-induced sleepwalking criminal defense is
      most often based on past clinical or legal reports that ingestion of alcohol
      directly 'triggers' sleepwalking or increased the risk of sleepwalking by
      increasing the quantity of slow wave sleep (SWS). A review of the sleep medicine
      literature found no sleep laboratory studies of the effects of alcohol on the
      sleep of clinically diagnosed sleepwalkers. However, 19 sleep laboratory studies
      of the effects of alcohol on the sleep of healthy non-drinkers or social drinkers
      were identified with none reporting a change in SWS as a percentage of total
      sleep time. However, in six of 19 studies, a modest but statistically significant
      increase in SWS was found in the first 2-4 h. Among studies of sleep in alcohol
      abusers and abstinent abusers, the quantity and percentage of SWS was most often
      reduced and sometimes absent. Claims that direct alcohol provocation tests can
      assist in the forensic assessment of these cases found no support of any kind in
      the medical literature with not a single report of testing in normative or
      patient groups and no reports of validation testing of any sort. There is no
      direct experimental evidence that alcohol predisposes or triggers sleepwalking or
      related disorders. A legal defense of sleepwalking resulting from voluntarily
      ingested alcohol should be consistent with the current state of art sleep science
      and meet generally accepted requirements for the diagnosis of sleepwalking and
      other parasomnias.

PMID- 17542951
TI  - Validation of actigraphy for determining sleep and wake in children with sleep
      disordered breathing.
AB  - There have been limited studies of the validation of actigraphy for the
      determination of sleep and wake in children and in this study we aimed to compare
      wrist actigraphy with polysomnography (PSG). We studied 45 children (29 M/16 F),
      aged between 1 and 12 years (5.8 +/- 2.7 years, mean +/- SD). Actigraphic data
      were collected during standard overnight PSG. Data from the actiwatch were
      analysed over four separate activity threshold settings (low, medium, high,
      auto). Actigraphic data were compared epoch-by-epoch with the matching PSG. Sleep
      time was not different from PSG values for the low or auto activity thresholds,
      but was significantly less on the medium and high activity thresholds (P < 0.05).
      In contrast, the low and auto activity thresholds significantly underestimated
      wake time (P < 0.05), whilst that recorded on the medium and high activity
      thresholds were not different to PSG values. Agreement rates across the
      thresholds were all high ranging from 85.1% to 88.6%. Predictive value for sleep
      and sensitivity were also high with values ranging from 91.6% to 94.9% and 90.1%
      to 97.7%, respectively. In contrast, predictive value for wake and specificity
      were low ranging between 46.7-65.6% and 39.4-68.9%, respectively. There was no
      effect of subject age, OAHI or PSG arousal index on AR for any of the activity
      thresholds. We conclude that actigraphy is a reliable method for determining
      sleep in children when compared against PSG. Actigraphy may be a useful tool in
      paediatric sleep clinics and research.

PMID- 17542952
TI  - The effect of short-term withdrawal from continuous positive airway pressure
      therapy on sympathetic activity and markers of vascular inflammation in subjects
      with obstructive sleep apnoea.
AB  - Obstructive sleep apnoea (OSA) is commonly associated with cardiovascular disease
      and sympathetic activation. However, it is unclear whether this association is
      independent of obesity and to what extent treatment with nasal continuous
      positive airway pressure (CPAP) alleviates the vascular inflammation that
      underpins cardiovascular disease. We therefore evaluated whether short-term
      withdrawal from CPAP therapy in subjects with moderate-severe OSA would result in
      increased levels of sympathetic activity and circulating inflammatory cytokines
      independent of weight. Vascular inflammatory markers (hsCRP, hsIL-6 and hsTNF
      alpha) were assessed in 20 subjects after one and seven nights of withdrawal from
      CPAP together with the hypoxia-responsive angiogenic marker VEGF and urinary
      catecholamines. Compared with baseline on CPAP, withdrawal from therapy resulted
      in an immediate return of OSA with an increase in RDI to 26.7 +/- 5.2 and 39.0 +/
      5.9 events per hour after one and seven nights without CPAP, respectively (both
      P < 0.0001). This was accompanied by a concomitant rise in daytime urinary
      noradrenaline (P < 0.0001) after seven nights CPAP withdrawal that was positively
      associated with the severity of hypoxaemia. In contrast, withdrawal from CPAP
      therapy was not accompanied by any change in measured cytokines or VEGF (all P >
      0.1). In conclusion, 1 week of CPAP withdrawal was associated with a return of
      OSA and a marked increase in sympathetic activity without a concomitant elevation
      of vascular inflammatory markers.

PMID- 17542953
TI  - Amygdala dysfunction in narcolepsy-cataplexy.
AB  - The blink reflex of acoustic startle reflex (ASR) is modulated by emotions and a
      loss of physiological aversive ASR potentiation is reported in humans following
      amygdala lesions. Patients with narcolepsy-cataplexy (NC) were found to have
      normal ASR, but they failed to exhibit startle potentiation during unpleasant
      stimuli. This absence of aversive ASR potentiation gives support to the
      hypothesis of an amygdala dysfunction in human NC.

PMID- 17542954
TI  - Prospective comparison of subjective arousal during the pre-sleep period in
      primary sleep-onset insomnia and normal sleepers.
AB  - Psychophysiological insomnia (PI) is the most common insomnia subtype,
      representing 12-15% of all sleep centre referrals. Diagnostic guidelines describe
      PI as an intrinsic sleep disorder involving both hyperarousal and learned sleep
      preventing associations. Whilst evidence for the first component is reasonably
      compelling, evidence for learned (conditioned) sleep effects is markedly lacking.
      Indeed, to date no study has attempted to capture directly the conditioned
      arousal effect assumed to characterize the disorder. Accordingly, the present
      study explored variations in subjective arousal over time in 15 PI participants
      (sleep onset type) and 15 normal sleepers (NS). Self-report measures of cognitive
      arousal, somatic arousal and sleepiness were taken at three time points: 3 h
      before bedtime (early to mid-evening); 1 h before bedtime (late evening); and in
      the bedroom at lights out (bedtime) across four, 24-h cycles. Fluctuations in
      mean arousal and sleepiness values, and in day-to-day variation were examined
      using analyses of variance. Participants with PI were significantly more
      cognitive aroused and significantly less sleepy relative to NS, within the
      bedroom environment. These results support the tenet of conditioned mental
      arousal to the bedroom, although competing explanations cannot be ruled out.
      Results are discussed with reference to extant insomnia models.

PMID- 17542955
TI  - European guidelines for accreditation of sleep medicine Centres.

PMID- 17542957
TI  - Zoonoses.

PMID- 17542958
TI  - Control versus no control: options for avian influenza H5N1 in Nigeria.
AB  - In January 2006, an outbreak of a highly pathogenic avian influenza (HPAI) was
      recorded in Nigeria for the first time. This present work describes an estimation
      of possible costs associated with a vaccination-based control policy added to
      other measures to restrict HPAI H5N1 virus infections. The evaluations used
      epidemiological and production data, including budgets necessary for the vaccine
      acquisition, distribution and administration in arriving at the final costs.
      Using decision tree and cost benefit analysis the economical benefits for Nigeria
      and countries with similar veterinary infrastructures, biosecurity and farming
      systems are calculated. The result indicated that a halting in the continued
      spread of the virus through effective control measure will be 52 times better
      than taking no action. This should help policy makers in deciding in favour of
      vaccination combined with other tools as an effective means of controlling avian
      influenza H5N1. * Control of HPAI H5N1 will best be understood by policy makers
      in financial terms. * Effective control through vaccination of poultry is much
      cheaper and reduces the chances of human zoonoses. * Poultry vaccination combined
      with other control measures will be the most effective means of control in most
      developing economies.

PMID- 17542959
TI  - Constraints to microbial food safety policy: opinions from stakeholder groups
      along the farm to fork continuum.
AB  - This exploratory qualitative study was conducted to identify constraints to
      microbial food safety policy in Canada and the USA from the perspective of
      stakeholder groups along the farm to fork continuum. Thirty-seven stakeholders
      participated in interviews or a focus group where semi-structured questions were
      used to facilitate discussion about constraints to policy development and
      implementation. An emergent grounded theory approach was used to determine themes
      and concepts that arose from the data (versus fitting the data to a hypothesis or
      a priori classification). Despite the plurality of stakeholders and the range of
      content expertise, participant perceptions emerged into five common themes,
      although, there were often disagreements as to the positive or negative
      attributes of specific concepts. The five themes included challenges related to
      measurement and objectives of microbial food safety policy goals, challenges
      arising from lack of knowledge, or problems with communication of knowledge
      coupled with current practices, beliefs and traditions; the complexity of the
      food system and the plurality of stakeholders; the economics of producing safe
      food and the limited resources to address the problem; and, issues related to
      decision-making and policy, including ownership of the problem and inappropriate
      inputs to the decision-making process. Responsibilities for food safety and for
      food policy failure were attributed to all stakeholders along the farm to fork
      continuum. While challenges regarding the biology of food safety were identified
      as constraints, a broader range of policy inputs encompassing social, economic
      and political considerations were also highlighted as critical to the development
      and implementation of effective food safety policy. Strategies to address these
      other inputs may require new, transdisciplinary approaches as an adjunct to the
      traditional science-based risk assessment model.

PMID- 17542960
TI  - Infectivity of scrapie prion protein (PrPSc) following in vitro digestion with
      bovine gastrointestinal microbiota.
AB  - The influence of a complex microflora residing in the gastrointestinal tract of
      cattle on the prion protein plays a crucial role with respect to early
      pathogenesis and the potential infectivity of faeces resulting in contamination
      of the environment. It is unknown whether infectious prion proteins, considered
      to be very stable, are inactivated by microbial processes in the gastrointestinal
      tract of animals during digestion. In our previous study it was shown that the
      scrapie-associated prion protein was degraded by ruminal and colonic microbiota
      of cattle, as indicated by a loss of anti-prion antibody 3F4 immunoreactivity in
      Western blot. Subsequently, in this study hamster bioassays with the pre-treated
      samples were performed. Although the PrP(Sc) signal was reduced up to
      immunochemically undetectable levels within 40 h of pre-treatment, significant
      residual prion infectivity was retained after degradation of infected hamster
      brain through the gastrointestinal microflora of cattle. The data presented here
      show that the loss of anti-prion antibody 3F4 immunoreactivity is obviously not
      correlated with a biological inactivation of PrP(Sc). These results highlight the
      deficiency of using Western blot in transmissible spongiform encephalopathies
      inactivation assessment studies and, additionally, point to the possibility of
      environmental contamination with faeces containing PrP(Sc) following an oral
      ingestion of prions.

PMID- 17542961
TI  - Assessing the within-herd prevalence of Coxiella burnetii milk-shedder cows using
      a real-time PCR applied to bulk tank milk.
AB  - Thirty-seven bulk tank milk (BTM) and individual milk samples of all contributing
      cows were tested for Coxiella burnetii detection by a real-time PCR assay and
      used to assess the relationship between the BTM PCR-response and (i) the within
      herd prevalence of milk-shedder cows and (ii) the proportion of heavy milk
      shedder cows. The within-herd prevalence of milk-shedder cows (i) was found to be
      significantly higher in herds with a positive BTM and (ii) increased
      significantly with the estimated titre in Coxiella burnetii obtained in positive
      BTM. The proportion of heavy milk-shedder cows among the milk-shedder cows
      increased significantly with an increased estimated titre in Coxiella burnetii in
      positive BTM. Therefore, a real-time PCR assay applied to BTM samples collected
      repeatedly over time appears to be a valuable tool to assess on a larger scale
      the status of herds towards Coxiella shedding, and to evaluate the efficiency of
      control actions aimed at controlling and/or preventing Coxiella shedding in dairy
      herds.

PMID- 17542962
TI  - Epidemiological study of non-systemic parasitism in dogs in southeast
      Mediterranean Spain assessed by coprological and post-mortem examination.
AB  - The prevalence and risk factors of non-systemic canine ecto- and endoparasitism
      and anthelminthic use in Murcia located at the centre of the Spanish
      Mediterranean coastal arch, was investigated by coprology and necropsy in up to
      275 pet, city shelter and stray dogs in 2001-2004. Faecal parasite stages were
      detected in 25% of dogs. Species frequency was 6-10% for Toxocara canis,
      Ancylostomatidae spp., Toxascaris leonina and Isospora canis, and 0.4-1% for
      Trichuris vulpis, Giardia lamblia, and Dipylidium caninum. Logistic regression
      indicated that the risk of intestinal parasitism was highest for dogs <or=1 year
      old, in the middle to low weight range and kept at the city shelter. Although
      risk factors varied according to the species, T. canis was most common in <1 year
      old and Ancylostomatidae spp. was more prevalent in older dogs. This suggests
      that the dominant species was Uncinaria spp. and not the more zoonotically
      important Ancylostoma spp. This was further supported by necropsy findings;
      however, the degree of agreement between post-mortem and coprological examination
      for intestinal parasites was generally poor. Necropsy revealed 10%G. lamblia,
      12%Taenia spp. 38%D. caninum infections. Fleas, ticks and lice were also found in
      38%, 6% and 2% of necropsied stray dogs. These results demonstrate the need for
      an urgent parasite control programme at the city dog shelter and the need to
      improve the owner's education on zoonotic risks, the proper use of
      anthelminthics, and other parasite control practices.

PMID- 17542963
TI  - Isolation and characterization of an Indian ORF virus from goats.
AB  - Isolation and characterization of an orf virus has been described here. The virus
      was isolated from an outbreak of 'scabby mouth' in goats in Northern India. Viral
      morphology from the scab biopsy revealed typical ovoid-shaped particles
      characteristic of Parapoxvirus. Virus was isolated from sonicated scab suspension
      and characterized by restriction enzyme (RE) analysis and sequencing of full
      length GM-CSF- and interleukin-2 inhibitory factor (GIF) gene. RE pattern of the
      virus did not show close resemblance to most of the orf viruses published
      earlier. However, it showed high sequence identity and closer phylogenetic
      relationship with previously published ORFV-SA00 strain, as evident from the
      nucleotide and deduced amino acid sequence of GIF gene.

PMID- 17542964
TI  - Influence of communal alpine pasturing on the spread of pestiviruses among sheep
      and goats in Austria: first identification of border disease virus in Austria.
AB  - The purpose of this investigation was to determine the influence of communal
      Alpine pasturing on the spread of pestivirus infections among sheep and goats.
      The study included 481 sheep from 23 farms and 131 goats from 26 farms pastured
      on separated Alpine meadows in the western part of Austria. At the starting of
      pasturing on the sheep meadow, 325 (67.6%) animals were seropositive, on the goat
      meadows in 16 (12.2%) samples antibodies to pestiviruses were detected. At the
      end of pasturing, 74 seronegative sheep and two seronegative goats had
      seroconverted. Between the beginning and the end of pasturing the seroprevalence
      in sheep increased significantly from 67.6% to 83% (P<0.05). Moreover, in the
      peripheral blood mononuclear cells of four sheep, pestivirus-specific RNA was
      detected before as well as after pasturing; these animals remained serologically
      negative throughout the investigation. They were, therefore, identified as
      persistently infected. Sequence analysis in the N(pro) region revealed that the
      detected pestiviruses were the same at genetic level and they were grouped into
      the Border disease virus (BDV)-3 genotype. No pestivirus RNA was found in goat
      samples. The results of this survey indicate that communal Alpine pasturing does
      play a key role in the spread of BDV. Moreover, BDV has been identified and
      characterized for the first time in sheep in Austria, which until then had been
      regarded as being free from BD.

PMID- 17542965
TI  - Porcine circovirus 2 replication in colostrum-deprived piglets following
      experimental infection and immune stimulation using a modified live vaccine
      against porcine respiratory and reproductive syndrome virus.
AB  - Porcine circovirus type 2 (PCV2) infection is now recognized as the major factor
      in the development of post-weaning multisystemic wasting syndrome (PMWS).
      Although Koch's postulates have been fulfilled for PCV2 and PMWS, the severe
      clinical expression of the disease observed in field cases has been difficult to
      reproduce experimentally. Some studies have demonstrated that immune stimulation
      associated with the use of some commercially available swine vaccines may trigger
      progression of PCV2 infection to disease and lesions characteristic of PMWS. Here
      we describe the effects on PCV2 infection in an experimental model following the
      use of a commercially available modified live vaccine to porcine respiratory and
      reproductive syndrome virus (PRRSV). Although none of the piglets infected with
      PCV2 developed clinical PMWS, the severity of microscopical lesions and the PCV2
      antigen load associated with these lesions were higher in the PRRSV-vaccinated
      piglets compared with those detected in the PCV2 only infected animals.

PMID- 17542977
TI  - Topical plus subconjunctival anaesthesia: foldable intraocular lens implantation
      in eyes without capsule support through a self-sealing incision.
AB  - PURPOSE: To evaluate the clinical outcomes of topical plus subconjunctival
      anaesthesia for secondary implantation of foldable intraocular lens (IOL) (Ophtec
      PC 425Y) in eyes without capsule support through a self-sealing incision.
      METHODS: We reviewed the medical records of 22 patients (22 eyes) who received
      topical plus subconjunctival anaesthesia for scleral fixation of a foldable IOL
      through small incision. The scleral incision technique was used for IOL scleral
      fixation. Twelve eyes had traumatic cataract, seven had postphacoemulsification
      complications and three were aphakic. We studied visual outcome, intraoperative
      complications and perioperative pain. Autorefractometry and keratometry
      measurements and central endothelial cell counts were evaluated 1 day
      preoperatively and 4 months postoperatively. The level of intraoperative pain was
      scored on a scale of 1-10, where 1 = no pain and 10 = severe pain. RESULTS:
      Nineteen patients (86%) tolerated the procedure well, giving pain scores of 1-3,
      and none required supplemental anaesthesia. The mean age of the patients was 60
      years. The postoperative best-corrected visual acuity (BCVA) ranged between
      20/100 and 20/25. Four months postoperatively, the mean myopic shift by
      autorefractometry was -1.25 dioptre (D) and the mean postoperative astigmatism
      was 1.75 D. The mean central corneal endothelial loss at 4 months was 12.24%
      (range 4.5-17.2%). Five microscopic hyphaema occurred intraoperatively. Four
      cystoid macular oedema and four peripheral anterior synechia were the only
      complications, each occurring at the final follow-up. CONCLUSION: Topical plus
      subconjunctival anaesthesia and scleral fixation of foldable IOL (Ophtec PC 425Y)
      was safe, quick, required a small incision, led to favourable visual outcomes and
      minimized the risk of intraoperative and postoperative complications in eyes
      without capsule support. However, a long-term study of a large population is
      required to confirm these findings.

PMID- 17542978
TI  - Hypotony maculopathy.
AB  - Hypotony maculopathy, first described in 1954 by Dellaporta, usually occurs after
      antiglaucomatous surgery or after perforating eye injuries; it is characterized
      by hypotony associated with fundus abnormalities, including papilloedema,
      vascular tortuosity and chorioretinal folds. In hypotony maculopathy, the scleral
      wall collapses inward, resulting in redundancy of the choroid and retina, leading
      to chorioretinal wrinkling. As the antero-posterior diameter of the vitreous
      cavity decreases, the very thick perivofeal retina surrounding the very thin
      foveal retina is thrown into radial folds around the fovea. It has been reported
      that hypotony maculopathy occurs in up to 20% of cases of glaucoma filtering
      surgery and has become more common after the introduction of antimetabolites.
      Young age, myopia, primary filtering surgery, systemic illnesses and elevated
      preoperative intraocular pressure (IOP) have been found to be associated with
      hypotony maculopathy. Hypotony maculopathy is treated with procedures designed to
      elevate IOP, which may reverse the inward scleral bowing and improve visual
      acuity. The successful treatment of hypotony maculopathy depends on the correct
      identification of its cause. Once the cause is detected, treatment should be
      employed as soon as possible because delayed normalization of the IOP may result
      in permanent macular chorioretinal changes and poor vision. This review will
      explore the definition, mechanisms, clinical findings and treatment of hypotony
      maculopathy.

PMID- 17542979
TI  - Coccygeal polypoid eccrine naevus.

PMID- 17542980
TI  - Variable pulsed light is less painful than light-emitting diodes for topical
      photodynamic therapy of actinic keratosis: a prospective randomized controlled
      trial.
AB  - BACKGROUND: Photodynamic therapy (PDT) of actinic keratosis (AK) using
      methylaminolaevulinate (MAL) is an effective and safe treatment option, but the
      procedure is painful. OBJECTIVES: To evaluate the efficacy and pain associated
      with variable pulsed light (VPL), a prospective, randomized, controlled split
      face study was performed. METHODS: Topical MAL-PDT was conducted in 25 patients
      with AK (n = 238) who were suitable for two-sided comparison. After incubation
      with MAL, irradiation was performed with a light-emitting diode (LED) (50 mW cm(
      2); 37 J cm(-2)) vs. VPL (80 J cm(-2), double pulsed at 40 J cm(-2), pulse train
      of 15 impulses each with a duration of 5 ms, 610-950 nm filtered hand piece)
      followed by re-evaluation up to 3 months. RESULTS: The pain during and after
      therapy was significantly lower with VPL irradiation [t (d.f. = 24) = 4.42, P <
      0.001]. The overall mean +/- SD infiltration and keratosis score at 3 months
      after treatment was 0.86 +/- 0.71 (LED system) vs. 1.05 +/- 0.74 (VPL device) (no
      statistically significant difference; P = 0.292). Patient satisfaction following
      both treatment modalities did not significantly differ at the 3-month follow up
      (P = 0.425). CONCLUSIONS: VPL used for MAL-PDT is an efficient alternative for
      the treatment of AK that results in complete remission and cosmesis equivalent to
      LED irradiation but causes significantly less pain.

PMID- 17542981
TI  - Myelodysplastic syndrome with pure red cell aplasia shows characteristic
      clinicopathological features and clonal T-cell expansion.

PMID- 17542982
TI  - Detection of FIP1L1-PDGFRA fusion by FISH.

PMID- 17542983
TI  - The immune thrombocytopenic purpura (ITP) bleeding score: assessment of bleeding
      in patients with ITP.
AB  - A method for objective quantification of bleeding symptoms in immune
      thrombocytopenic purpura (ITP) has not been established. The ITP Bleeding Scale
      (IBLS) is a novel bleeding assessment system comprising 11 site-specific grades.
      Implementation of the IBLS on 100 patient visits revealed that although platelet
      count and large platelet count correlated well with bleeding symptoms overall,
      this relationship disappeared in marked thrombocytopenia. The IBLS is a useful
      clinical tool for monitoring bleeding and may be used to aid the development of
      laboratory parameters that correlate with underlying bleeding propensity in
      thrombocytopenia.

PMID- 17542985
TI  - Increased Akt and phosphorylated Akt expression are associated with malignant
      biological features of prostate cancer in Japanese men.
AB  - OBJECTIVE: To investigate the relationship between the expression of Akt (a
      serine/threonine kinase that plays a central role in tumorigenesis),
      phosphorylated Akt (p-Akt), prostate cancer tumour grade, androgen receptor (AR)
      staining score, and Ki67 labelling index (LI) in Japanese men. PATIENTS,
      MATERIALS AND METHODS: The expression and activation of the cell survival protein
      Akt was analysed by immunohistochemical staining of paraffin-embedded tissue
      microarray sections of prostate carcinoma taken from 52 Japanese men who under
      radical prostatectomy. The correlation between the expression of Akt and p-Akt,
      and their relationship to primary Gleason grade, AR expression and Ki-67 LI was
      investigated. RESULTS: The expression of Akt and p-Akt were positively related to
      primary Gleason grade (Fisher's exact test, P = 0.002 and P = 0.032,
      respectively). Both AR-staining score and Ki67 LI were were positively related to
      the expression of Akt (both P < 0.001) and p-Akt (P < 0.001 and P = 0.008,
      respectively). There was a significant positive correlation between the
      expression of Akt and p-Akt (Spearman's correlation, r = 0.644, P < 0.001).
      CONCLUSIONS: Increased expression of both Akt and p-Akt were associated with
      higher tumour grade as well as a higher AR-staining score and Ki67 LI. These data
      indicate that Akt and p-Akt might be molecular markers for detecting malignant
      biological features of prostate cancer in the Japanese population.

PMID- 17542984
TI  - Targeting NF-kappaB pathway with an IKK2 inhibitor induces inhibition of multiple
      myeloma cell growth.
AB  - The pathophysiologic basis for multiple myeloma (MM) has been attributed to the
      dysregulation of various paracrine or autocrine growth factor loops and to
      perturbations in several signal transduction pathways including IkappaB
      kinase/nuclear factor-kappaB (IKK/NF-kappaB). The present study aimed at
      investigating the effect of a pharmaceutical IKK2 inhibitor, the
      anilinopyrimidine derivative AS602868, on the in vitro growth of 14 human MM cell
      lines (HMCL) and primary cells from 13 patients. AS602868 induced a clear dose
      dependent inhibition of MM cell growth on both HMCL and primary MM cells, which
      was the result of a simultaneous induction of apoptosis and inhibition of the
      cell cycle progression. Combination of AS602868 with suboptimal doses of
      melphalan or Velcade showed an additive effect in growth inhibition of HMCL.
      AS602868 also induced apoptosis of primary myeloma cells. Importantly, AS602868
      did not alter the survival of other bone marrow mononuclear cells (CD138(-)) co
      cultured with primary MM (CD138(+)) cells, except for CD34(+) haematopoietic stem
      cells. The results demonstrate the important role of NF-kappaB in maintaining the
      survival of MM cells and suggest that a pharmacological inhibition of the NF
      kappaB pathway by the IKK2 inhibitor AS602868 can efficiently kill HMCL and
      primary myeloma cells and therefore might represent an innovative approach for
      treating MM patients.

PMID- 17542986
TI  - Bad expression influences time to androgen escape in prostate cancer.
AB  - OBJECTIVE: To assess the role of selected downstream Bcl-2 family members (Bad,
      Bax, Bcl-2 and Bcl-xL) in the development of androgen-independent prostate cancer
      (AIPC), as androgen-deprivation therapy is the treatment of choice in advanced
      prostate cancer, yet patients generally relapse and progress to an AI state
      within 18-24 months. PATIENTS, MATERIALS AND METHODS: The patient cohort was
      established by retrospectively selecting patients with prostate cancer who had an
      initial response to androgen-deprivation therapy, but subsequently relapsed with
      AIPC. In all, 58 patients with prostate cancer were included with matched
      androgen-dependent (AD) and AI prostate tumours available for immunohistochemical
      analysis; two independent observers using a weighted-histoscore method scored the
      staining. Changes in Bad, Bax, Bcl-2 and Bcl-xL expression during transition to
      AIPC were evaluated and then correlated to known clinical variables. RESULTS:
      High Bad expression in AD tumours was associated with an increased time to
      biochemical relapse (P = 0.007) and a trend towards improved overall survival (P
      = 0.053). There were also trends towards a decrease in Bad (P = 0.068) and Bax (P
      = 0.055) expression with progression to AIPC. There were no significant results
      for Bcl-2 or Bcl-xL. CONCLUSION: There is evidence to suggest that Bad expression
      levels at diagnosis influence time to biochemical relapse and overall survival,
      and that levels of pro-apoptotic proteins Bad and Bax fall during AIPC
      development. Bad might therefore represent a possible positive prognostic marker
      and potential therapeutic target for AIPC in the future.

PMID- 17542987
TI  - The impact of reducing the prostate-specific antigen threshold and including
      isoform reflex tests on the performance characteristics of a prostate-cancer
      detection programme.
AB  - OBJECTIVE: To assess the effects on the performance characteristics, in a
      prostate-cancer detection programme using prostate-specific antigen (PSA) levels,
      of a lower PSA threshold and the incorporation of reflex (free or complexed PSA)
      tests. METHODS: We reviewed publications and extracted data on PSA distributions
      and performance characteristics of the PSA test and isoform tests from population
      based surveys. We estimated the rate of biopsy, cancers detected, and cancers
      missed that would result from lowering PSA thresholds and including reflex
      testing. RESULTS: Lowering the PSA threshold for biopsy referral to 2 ng/mL would
      increase the number of referrals from 110 to 230 per 1000 men tested, with most
      of the extra biopsies being among men with no cancer, i.e. an increase from 74 to
      172 per 1000 men tested. However, this increased testing would result in an
      increase in the cancer-detection rate from 3.6% to 5.8%. Including a reflex test
      for men with moderately elevated PSA levels has little effect on programme
      performance, with only a modest (10-15%) reduction in unnecessary biopsies and a
      small increase in the numbers of missed cancers. CONCLUSIONS: Lowering PSA
      thresholds, with or without the concurrent introduction of reflex tests, would
      increase both the numbers of cancers detected and the number of patients referred
      for biopsy procedures, of which most would be unnecessary. As the extra cancers
      detected are likely to be clinically localized, and with no evidence that their
      treatment improves the outcome of the disease, such changes place a possibly
      unjustified additional burden on the healthcare provider.

PMID- 17542988
TI  - Genetic determinants of prostate cancer risk.

PMID- 17542989
TI  - Short interval between symptom onset and medical care as an indication of rapid
      onset of interstitial cystitis/painful bladder syndrome.
AB  - OBJECTIVE: To assess how many patients with interstitial cystitis/painful bladder
      syndrome (IC/PBlS) obtain medical care soon after symptom onset, and to determine
      how these patients differ from those who have medical care later. PATIENTS AND
      METHODS: In a risk-factor study of IC/PBlS, we recruited women with IC/PBlS
      symptoms of < or =12 months' duration and carefully identified the onset date,
      first medical encounter and early clinical findings. RESULTS: Of 138 women with
      IC/PBlS for < or =12 months, 49% sought medical care within 7 days and another
      31% within 4 weeks. These patients had no easier access to medical care but
      rather experienced symptoms differently, with more evidence for discomfort and
      inflammation. However, subsequently they did not differ from those with more
      gradual onset in features indicative of IC/PBlS, i.e. Hunner's ulcers, petechial
      haemorrhages, symptoms, medications, or quality of life. CONCLUSIONS: A shorter
      time to the first medical encounter was not a function of greater access to
      medical care but instead was associated with more discomfort and evidence of
      inflammation, as distinct from those with more gradual onset. The 6-month follow
      up of both groups indicated that no significant differences in IC/PBlS symptoms
      persisted. A careful study of rapid-onset IC/PBlS might provide clues to the
      pathogenesis of this enigmatic disease.

PMID- 17542990
TI  - Structural and functional consequences of single amino acid substitutions in the
      pyrimidine base binding pocket of Escherichia coli CMP kinase.
AB  - Bacterial CMP kinases are specific for CMP and dCMP, whereas the related
      eukaryotic NMP kinase phosphorylates CMP and UMP with similar efficiency. To
      explain these differences in structural terms, we investigated the contribution
      of four key amino acids interacting with the pyrimidine ring of CMP (Ser36,
      Asp132, Arg110 and Arg188) to the stability, catalysis and substrate specificity
      of Escherichia coli CMP kinase. In contrast to eukaryotic UMP/CMP kinases, which
      interact with the nucleobase via one or two water molecules, bacterial CMP kinase
      has a narrower NMP-binding pocket and a hydrogen-bonding network involving the
      pyrimidine moiety specific for the cytosine nucleobase. The side chains of Arg110
      and Ser36 cannot establish hydrogen bonds with UMP, and their substitution by
      hydrophobic amino acids simultaneously affects the K(m) of CMP/dCMP and the
      k(cat) value. Substitution of Ser for Asp132 results in a moderate decrease in
      stability without significant changes in K(m) value for CMP and dCMP. Replacement
      of Arg188 with Met does not affect enzyme stability but dramatically decreases
      the k(cat)/K(m) ratio compared with wild-type enzyme. This effect might be
      explained by opening of the enzyme/nucleotide complex, so that the sugar no
      longer interacts with Asp185. The reaction rate for different modified CMP
      kinases with ATP as a variable substrate indicated that none of changes induced
      by these amino acid substitutions was 'propagated' to the ATP subsite. This
      'modular' behavior of E. coli CMP kinase is unique in comparison with other NMP
      kinases.

PMID- 17542991
TI  - Substrate and inhibitor specificity of Mycobacterium avium dihydrofolate
      reductase.
AB  - Dihydrofolate reductase (EC 1.5.1.3) is a key enzyme in the folate biosynthetic
      pathway. Information regarding key residues in the dihydrofolate-binding site of
      Mycobacterium avium dihydrofolate reductase is lacking. On the basis of previous
      information, Asp31 and Leu32 were selected as residues that are potentially
      important in interactions with dihydrofolate and antifolates (e.g. trimethoprim),
      respectively. Asp31 and Leu32 were modified by site-directed mutagenesis, giving
      the mutants D31A, D31E, D31Q, D31N and D31L, and L32A, L32F and L32D. Mutated
      proteins were expressed in Escherichia coli BL21(DE3)pLysS and purified using His
      Bind resin; functionality was assessed in comparison with the recombinant wild
      type by a standard enzyme assay, and growth complementation and kinetic
      parameters were evaluated. All Asp31 substitutions affected enzyme function;
      D31E, D31Q and D31N reduced activity by 80-90%, and D31A and D31L by > 90%. All
      D31 mutants had modified kinetics, ranging from three-fold (D31N) to 283-fold
      (D31L) increases in K(m) for dihydrofolate, and 12-fold (D31N) to 223 077-fold
      (D31L) decreases in k(cat)/K(m). Of the Leu32 substitutions, only L32D caused
      reduced enzyme activity (67%) and kinetic differences from the wild type (seven
      fold increase in K(m); 21-fold decrease in k(cat)/K(m)). Only minor variations in
      the K(m) for NADPH were observed for all substitutions. Whereas the L32F mutant
      retained similar trimethoprim affinity as the wild type, the L32A mutation
      resulted in a 12-fold decrease in affinity and the L32D mutation resulted in a
      seven-fold increase in affinity for trimethoprim. These findings support the
      hypotheses that Asp31 plays a functional role in binding of the substrate and
      Leu32 plays a functional role in binding of trimethoprim.

PMID- 17542992
TI  - Molecular characterization of a blood-induced serine carboxypeptidase from the
      ixodid tick Haemaphysalis longicornis.
AB  - Ticks feed exclusively on blood to obtain their nutrients, but the gene products
      that mediate digestion processes in ticks remain unknown. We report the molecular
      characterization and possible function of a serine carboxypeptidase (HlSCP1)
      identified in the midgut of the hard tick Haemaphysalis longicornis. HlSCP1
      consists of 473 amino acids with a peptidase S10 family domain and shows
      structural similarity with serine carboxypeptidases reported from other
      arthropods, yeasts, plants and mammals. Endogenous HlSCP1 is strongly expressed
      in the midgut and is supposed to localize at lysosomal vacuoles and on the
      surface of epithelial cells. Endogenous HlSCP1, identified as a 53 kDa protein
      with pI value of 7.5, was detected in the membrane/organelle fraction isolated
      from the midgut, and its expression was upregulated during the course of blood
      feeding. Enzymatic functional assays revealed that a recombinant HlSCP1 (rHlSCP1)
      expressed in yeast efficiently hydrolyzed the synthetic substrates specific for
      cathepsin A and thiol protease over a broad range of pH and temperature values.
      Furthermore, rHlSCP1 was shown to cleave hemoglobin, a major component of the
      blood-meal. Our results suggest that HlSCP1 may play a vital role in the
      digestion of the host's blood-meal.

PMID- 17542993
TI  - COX-2 expression in lobular in situ neoplasia of the breast: correlation with
      histopathological grading system according to the Tavassoli classification.
AB  - AIMS: There is considerable evidence to link cyclooxygenase (COX)-2 to the
      development of cancer. The aim of this study was to assess COX-2 expression and
      its subcellular localization in lobular in situ neoplasia (LIN) of the breast and
      to verify differences in COX-2 expression between different grades of lesions
      according to the Tavassoli classification. METHODS AND RESULTS: We analysed the
      expression of COX-2 protein by immunohistochemistry in tissue samples of 51 LIN
      lesions classified into three grades according to the Tavassoli classification.
      COX-2 immunostaining was observed in 78.4% of LIN samples and showed a prevalent
      membranous rather than cytoplasmic pattern. COX-2 was expressed in 16/17 (94.1%)
      LIN1, 22/25 (88%) LIN2 and 2/9 (22.2%) LIN3. As regards COX-2 expression, a
      statistically significant difference was found between LIN1 and LIN3 (P = 0.001)
      and between LIN2 and LIN3 (P =0.001). No difference was found between LIN1 and
      LIN2. Moreover, a significant negative correlation was found between LIN grade
      and COX-2 expression (P < 0.0001). CONCLUSIONS: COX-2 is highly expressed in LIN,
      supporting a role for this protein in the early stage of breast carcinogenesis,
      representing the rationale for using COX-2 selective inhibitors in the earliest
      stages of breast cancer.

PMID- 17542994
TI  - Squamous cell carcinoma arising in mature cystic teratoma of the ovary: an
      immunohistochemical analysis of its tumorigenesis.
AB  - AIMS: Squamous cell carcinoma (SCC) is the most common form of malignant
      transformation in mature cystic teratoma (MCT) of the ovary. Some investigators
      have suggested the possibility of origin from columnar epithelium. The aim of
      this study was to analyse such tumours immunohistochemically to elucidate their
      histogenesis. METHODS AND RESULTS: The expression of cytokeratin (CK) 10 and CK18
      was examined in 21 samples of SCC arising in MCT. The expression of CK10 and CK18
      was also assessed in SCCs arising in different organs (skin, vulva, lung and
      uterine cervix) for the purpose of comparison. SCC in MCT expressed CK10 in 7/21
      cases [33.3%, 95% confidence interval (CI) 0.12-0.53] and CK18 in 14/21 cases
      (66.7%, 95% CI 0.46-0.87). SCC in MCT expressed CK10 less frequently, but CK18
      more frequently, as is the case in SCCs of the uterine cervix (CK10, 20%; CK18,
      70%) and the lung (CK10, 5%; CK18, 90%), both of which are derived from columnar
      epithelium by squamous metaplasia. CONCLUSIONS: SCC in MCT may be derived from
      metaplastic squamous epithelium.

PMID- 17542995
TI  - API2-MALT1 chimeric transcript-positive gastroduodenal MALT lymphoma with
      subsequent development of adenocarcinoma as a collision tumour over a clinical
      course of 7 years.

PMID- 17542996
TI  - Rural Organisation of Acute Stroke Teams project.
AB  - BACKGROUND: Improving the care of stroke patients is a national priority for the
      health system in Australia. In rural areas the challenges may be greater.
      Although best-practice guidelines for acute and subacute stroke care are well
      established, their general uptake appears to be limited and implementation
      strategies are required to promote the use of this evidence-based care. The Rural
      Organisation of Australian Stroke Teams (ROAST) project sought to promote the
      evidence-based stroke practice in rural hospitals. METHODS: This was a
      prospective observational project designed to improve the services provided to
      rural stroke patients, primarily through better organisation of care on general
      medical wards and emergency departments. Using recognized support strategies, we
      encouraged the use of nationally recognized key performance indicators and
      provided audit and feedback of adherence to these indicators to participating
      hospitals. RESULTS: Six Victorian hospitals participated in this initial phase of
      the ROAST project. Information was collected on 348 patients. Ten of the 11
      indicators showed greater than 10% improvement in adherence levels and by the end
      of the project period compared favourably to levels of adherence described in
      metropolitan hospitals. CONCLUSION: The ROAST projected supported a network of
      clinicians to implement evidence-based guidelines in acute stroke care in the
      setting of general medical wards. In doing so, this project has shown that it is
      quite feasible to deliver best-practice care to stroke patients in rural
      Australia.

PMID- 17542997
TI  - Geriatric syndromes as predictors of adverse outcomes of hospitalization.
AB  - AIMS: The aim of this study was to determine the association between the common
      geriatric syndromes and predefined adverse outcomes of hospitalization and to
      identify the most important independent predictors of adverse outcomes using
      information gained within 24 h of admission in older general medical patients.
      METHODS: A prospective longitudinal cohort study of patients aged > or =75 years
      admitted to the rapid assessment medical unit in a teaching hospital was carried
      out. The role of geriatric syndromes in predicting outcomes was examined in
      univariate and multivariate models. The outcome measures were (i) length of
      hospital stay (LOS) of 28 days or more, (ii) institutionalization or change in
      residential care status to a more dependent category at discharge or during 3
      months post-discharge, (iii) unplanned readmissions during 3 months and (iv)
      mortality in hospital or 3 months post-discharge. RESULTS: The presence of
      geriatric syndromes was significantly associated with increased LOS and
      institutionalization or change in residential care status to a more dependent
      category. The factors most predictive of these outcomes were impaired pre
      admission functional status in activities of daily living, recurrent falls,
      urinary incontinence and supported living arrangements. The geriatric syndromes
      appeared less important in predicting unplanned readmission and death.
      CONCLUSION: The presence of geriatric syndromes in older general medical patients
      is an important determinant of adverse outcomes of hospitalization, particularly
      of LOS and admission to residential care. The predictors most useful for
      screening patients for these outcomes, within 24 h of admission, appear to be the
      presence of certain pre-existing geriatric syndromes before admission.

PMID- 17542998
TI  - Pilot study of an outpatient-based approach for advanced lymphoma using
      vinorelbine, gemcitabine and filgrastim.
AB  - BACKGROUND: Vinorelbine and gemcitabine have demonstrable single-agent activity
      against lymphoma, show differing toxicity profiles and can be given in an
      outpatient setting. AIMS: We have evaluated the feasibility of an outpatient
      based combination of vinorelbine and gemcitabine with filgrastim support (VGF) in
      patients with advanced lymphoma. METHODS: An open-label, single-arm study of 40
      consecutive patients with relapsed (n = 24) or refractory (n = 16) lymphoma was
      undertaken. The median number of prior regimens was three (range 1-11) and 12 had
      undergone prior stem cell transplantation. Patients received vinorelbine 25
      mg/m(2) and gemcitabine 1000 mg/m(2) on days 1 and 8 of each 21-day cycle.
      Patients showing no response after two cycles (early response) were offered
      alternative therapy. Responding patients received two more cycles. Primary end
      points were the early and overall response rates. RESULTS: One hundred and
      sixteen cycles of therapy were delivered. Hospital admissions were required
      following 27 treatment cycles (24%), predominantly following cycle 1. Febrile
      neutropenia followed 6% of cycles. The early and overall response rates on an
      intention-to-treat basis were 60 and 53%, respectively. Responses for peripheral
      T-cell lymphoma and Hodgkin lymphoma were particularly encouraging, 70 and 75%,
      respectively. With a median follow up of 34 months overall survival for the
      entire cohort at 2 years is 50%. Furthermore, for the 23 patients who did not
      receive high-dose consolidative therapy 2-year survival was 35%. CONCLUSIONS:
      Vinorelbine and gemcitabine with filgrastim support can be safely delivered in an
      outpatient setting and shows clinically meaningful activity against a range of
      advanced lymphoma subtypes.

PMID- 17542999
TI  - Has the use of disease-modifying anti-rheumatic drugs changed as a consequence of
      controlled access to high-cost biological agents through the Pharmaceutical
      Benefits Scheme?
AB  - BACKGROUND: A prerequisite for access to biological agents for the treatment of
      rheumatoid arthritis under Australia's Pharmaceutical Benefits Scheme (PBS) is
      evidence of an adequate trial of conventional disease-modifying anti-rheumatic
      drugs (DMARDs). The aim of this study was to examine whether there were changes
      in prescribing DMARDs since the introduction of the PBS criteria for access to
      biologicals in August 2003. METHODS: A retrospective study was undertaken of the
      national use of DMARDs in the period before and after the introduction of
      biologicals under the PBS. Dispensing data were analysed for changes in patterns
      of DMARD prescription rates (2000-2005). RESULTS: There were 2 887 746
      prescriptions for DMARDs between August 2000 and June 2005. PBS prescriptions
      accounted for 95% of these. Government expenditure for the DMARDs was $A156m.
      Trends in the use of DMARDs remained relatively steady over the study period
      without a significant change around the time the PBS criteria for biologicals
      were introduced. Use of hydroxychloroquine and leflunomide increased steadily,
      use of methotrexate and sulfasalazine was stable and use of gold preparations and
      penicillamine was considerably lower during this 5-year period. CONCLUSION:
      Introduction of PBS criteria for access to biologicals did not alter the trends
      in use of DMARDs based on national dispensing data. This study emphasized the
      value that would accrue from availability of more comprehensive, de-identified,
      individual patient data that would enable more detailed examination of the use of
      medicines. These data are available, but cannot be easily accessed. It is time to
      make the data available for approved, ethical research in the interests of better
      outcomes from medicines supplied under PBS.

PMID- 17543000
TI  - Sleep health New South Wales: chronic sleep restriction and daytime sleepiness.
AB  - AIMS: The aim of this study was to provide the first population-based
      descriptions of typical sleep duration and the prevalence of chronic sleep
      restriction and chronic sleepiness in community-dwelling Australian adults.
      METHODS: Ten thousand subjects randomly selected from the New South Wales
      electoral roll, half aged 18-24 years and the other half aged 25-64 years were
      posted a questionnaire asking about sleep behaviour, sleepiness and sleep
      disorders. RESULTS: Responses were received from 3300 subjects (35.6% response
      rate). The mean +/- standard deviation of sleep duration was 7.25 +/- 1.48
      h/night during the week and 7.53 +/- 2.01 h/night in the weekends. Of the working
      age group, 18.4% reported sleeping less than 6.5 h/night. Chronic daytime
      sleepiness was present in 11.7%. Logistic modelling indicated that the
      independent risk factors for excessive daytime sleepiness were being older,
      sleeping less than 6.5 h per night during the week, getting qualitatively
      insufficient sleep, having at least one symptom of insomnia and lacking
      enthusiasm (marker of depression). CONCLUSION: In New South Wales almost one
      fifth of the people are chronically sleep restricted and 11.7% are chronically
      sleepy. Chronic sleepiness was most commonly associated with voluntarily short
      sleep durations and symptoms of insomnia and depression. If the experimentally
      observed health effects of sleep restriction also operate at a population level,
      this prevalence of chronic sleep restriction is likely to have a significant
      influence on public health in Australia.

PMID- 17543001
TI  - Hepatocellular carcinoma in Sydney South West: late symptomatic presentation and
      poor outcome for most.
AB  - BACKGROUND: Hepatocellular cancer (HCC) is a serious complication of cirrhosis
      and chronic hepatitis B infection. The aim of the study was to determine the
      characteristics of patients with HCC presenting within the South West Sydney
      area, including an analysis of the rates and benefits of hepatocellular
      surveillance. METHODS: Data from patients with HCC presenting to Liverpool and
      Bankstown Hospitals from July 1993 to June 2003 were analysed retrospectively,
      predominantly from hospital records. RESULTS: Of the 151 HCC patients, 41% were
      Asian born. Most of the patients required an interpreter. Chronic viral hepatitis
      infection was present in 91 patients, of whom only 7% had previously received
      antiviral therapy. Alcohol alone was considered responsible in 31 patients.
      Cirrhosis could be documented in 58% of patients. Most of the patients (75%)
      presented symptomatically. The median survival was 5.1 months. When HCC was
      detected by surveillance, the tumours were slightly but not significantly more
      likely to be operable and the patients tended to be offered some form of active
      treatment more frequently. Multivariate analysis identified detection by
      surveillance, lower Child-Pugh score, smaller tumour size and eligibility for
      some form of treatment to be associated with a more favourable outcome.
      CONCLUSION: We observed low rates of surveillance for HCC, low recognition of
      cirrhosis before development of HCC and low rates of prior treatment of viral
      hepatitis. The poor outcome of HCC in the small group who had some sort of
      community surveillance is also a concern requiring further investigation.

PMID- 17543002
TI  - Drug utilization evaluation of i.v. paracetamol at a large teaching hospital.
AB  - BACKGROUND: I.v. paracetamol has recently become available in Australia for the
      treatment of pain when the oral or rectal administration route is not accessible.
      Our primary aim was to assess compliance with prescribing guidelines and our
      secondary aim to evaluate the safety of i.v. paracetamol use (4 g/day) and the
      effect of patient comorbidities on drug safety. METHODS: Eighty-five consecutive
      patients were identified through the pharmacy dispensing system at a 900-bed,
      metropolitan, primary care and tertiary referral hospital over a period of 7
      months from December 2005 to June 2006. Cross-sectional evaluation by patient
      interview, review of medical records and pathology parameters were carried out.
      The study has been approved by the Royal Brisbane and Women's Hospital Human
      Research Ethics Committee. RESULTS: I.v. paracetamol was given for pain following
      abdominal surgery (90%) and musculoskeletal pain (10%). The comorbid conditions
      included severe renal impairment (9.4%), alcohol dependence (3.5%), pre-existing
      liver failure (2.4%) and malnutrition (18.8%). Prescribing guidelines were not
      adhered to in 25% of patients. The main cause for discordance observed in 90% of
      this group was the administration of i.v. paracetamol despite the presence of an
      alternative route of administration. Eight patients received i.v. paracetamol
      despite not having had a surgical procedure. Twelve patients received i.v.
      paracetamol for longer than 48 h; no injection site reactions or toxicity were
      noted. CONCLUSION: A lack of concordance between i.v. paracetamol use and
      prescribing guidelines was identified. There were no new safety concerns.

PMID- 17543003
TI  - How compliant are we with guidelines for coronary angiography in clinical
      practice?
AB  - BACKGROUND: The American College of Cardiology and American Heart Association
      have published guidelines for coronary angiography. We evaluated the compliance
      rate with these guidelines in clinical practice, its correlation to results of
      angiography and aimed to identify problem areas of non-compliance. METHODS: We
      prospectively evaluated 802 consecutive referrals for coronary angiography over 5
      months in 2002 in a tertiary referral hospital. These referrals were assessed by
      two independent reviewers blinded to the results of angiography. RESULTS: Patient
      age was 62 +/- 11 years (522 men, 433 inpatients, 369 day-only patients).
      Referrals were outside published guidelines in 34.3 and 36.2% as evaluated by the
      two reviewers (concordance rate 88.2%, kappa = 0.74, p < 0.001). Intraobserver
      agreement was 97.5%. The rate of angiography showing either normal arteries or
      only minor diseases (<50%) was higher for referrals outside guidelines (68.4 vs
      22.6%, P < 0.001). Compliance rate was high with indications of non-ST-elevation
      myocardial infarction (99.2%) and ST-elevation myocardial infarction (95.8%),
      valvular disease (80%) and arrhythmia (80%). Compliance rate was lower with
      assessment of dyspnoea or heart failure (74.3%) and before non-cardiac surgery
      (72.7%) and was particularly low with assessment of chest pain (53.2%). Younger
      age (odds ratio (OR) 1.04, P < 0.001), female sex (OR 2.67, P < 0.001), day-only
      procedure (OR 2.27, P < 0.001) and non-invasive cardiologist referrer (OR 1.41, P
      = 0.046) were independent predictors of non-compliance. CONCLUSION: Referrals for
      coronary angiography were outside guidelines in a significant proportion of
      patients. Rate of negative angiography was higher when the referrals were outside
      guidelines. Problematic areas of non-compliance could be identified. Measures
      specifically targeting these areas may be more effective in improving the overall
      guideline compliance in clinical practice.

PMID- 17543004
TI  - Residential exposure to electric power transmission lines and risk of
      lymphoproliferative and myeloproliferative disorders: a case-control study.
AB  - BACKGROUND: Studies have shown an association between electromagnetic fields and
      childhood leukaemia. The aim of this study was to determine whether there is an
      increased risk of lymphoproliferative disorders (LPD) or myeloproliferative
      disorders (MPD) associated with residence < or =300 m from high-voltage power
      lines. METHODS: Case-control study of 854 patients diagnosed with LPD or MPD
      (including leukaemia, lymphoma and related conditions) aged 0-94 years comprising
      all cases diagnosed in Tasmania between 1972 and 1980. Controls were individually
      matched for sex and approximate age at the time of diagnosis. RESULTS: Compared
      with those who had always lived >300 m from a power line, those who had ever
      lived within 50 m had an odds ratio (OR) of 2.06 (95% confidence interval 0.87
      4.91) for developing LPD or MPD (based on 768 adult case-control pairs); those
      who had lived between 50 and 300 m had an OR of 1.30 (0.88-1.91). Adults who had
      lived within 300 m of a power line during the first 15 years of life had a
      threefold increase in risk (OR 3.23; 1.26-8.29); those who had lived within the
      same distance aged 0-5 years had a fivefold increase in risk (OR 4.74; 0.98
      22.9). These associations were strengthened when analyses were repeated for 201
      pairs with entirely Tasmanian residential histories. CONCLUSION: Although
      recognizing that this study has limitations, the results raise the possibility
      that prolonged residence close to high-voltage power lines, especially early in
      life, may increase the risk of the development of MPD and LPD later.

PMID- 17543005
TI  - D-dimer concentration increases with age reducing the clinical value of the D
      dimer assay in the elderly.
AB  - BACKGROUND: The D-dimer assay is used as an exclusion test in the assessment of
      suspected venous thromboembolic disease; patients with a negative result have a
      low probability of thrombosis. We reviewed the D-dimer results from a hospital
      and community laboratory using the vidas D-dimer test to assess the influence of
      age on the D-dimer assay. METHODS: D-dimer results from 6631 unselected patients
      aged more than 16 years were analysed in four age groups and it was shown that
      the median D-dimer concentration increased with age (16-40 years, 294 ng/mL; 40
      60 years, 387 ng/mL; 60-80 years; 854 ng/mL; >80 years, 1397 ng/mL). To test the
      effect of age on the assay specificity, a cohort of 1897 patients with suspected
      venous thromboembolic disease was analysed separately. Patients with a negative D
      dimer were discharged without further investigation. Patients with a positive
      result and a clinical suspicion of thrombosis underwent further investigation.
      One hundred and sixty-five deep vein thrombosis or pulmonary embolus cases were
      identified. RESULTS: The assay specificity decreased with age from 70% in
      patients less than 40 years to below 5% in patients more than 80 years. Receiver
      operator curves were prepared for each age group and the effect of altering the
      threshold value was analysed. In patients 60-80 years old a threshold value of
      1000 ng/mL increased assay specificity to 55% without loss of assay sensitivity.
      CONCLUSION: The vidas D-dimer assay with a threshold value of 500 ng/mL has
      little clinical value as an exclusion test in patients more than 80 years old.
      The assay specificity is poor (26%) in patients aged 60-80 years but could be
      improved by increasing the threshold value to 1000 ng/mL. We believe that this
      should be tested in a prospective trial.

PMID- 17543006
TI  - Withholding anticoagulation after a negative computed tomography pulmonary
      angiogram as a stand-alone imaging investigation: a prospective management study.
AB  - BACKGROUND: Accurate diagnosis of pulmonary embolism (PE) is essential and it is
      not clear whether a computed tomography pulmonary angiogram (CTPA) could be used
      as a stand-alone imaging investigation. The aim of the study was to test the
      accuracy of the clinical outcome of a negative CTPA as a stand-alone imaging
      investigation to exclude PE. METHODS: Five hundred and thirty-four consecutive
      patients who had a CTPA for diagnosis or exclusion of PE were recruited from
      March 2003 to October 2004. Four hundred and ninety-four patients had a helical
      CTPA as a stand-alone imaging investigation for diagnosis or exclusion of PE. A 3
      month post-CTPA follow up was carried out in all patients to establish the
      clinical outcome accuracy of a negative CTPA as a stand-alone imaging
      investigation. RESULTS: There were 387 (78.3%) negative and 107 (21.7%) positive
      CTPA examinations. The average age of the patients was 57.16 years (standard
      deviation 18.57). Among those with a negative CTPA who survived, one patient had
      deep vein thrombosis and 342 patients had no evidence of an episode of venous
      thromboembolism or PE at the 3-month follow up. Thirty-eight patients died within
      the 3-month follow-up period and one patient's death was attributed to suspected
      PE. The negative predictive value of a CTPA is 99.5% (95% confidence interval
      98.1-99.9%). CONCLUSION: Helical negative CTPA examination excludes clinically
      significant PE as a stand-alone imaging investigation. Where concurrent deep vein
      thrombosis is suspected, lower limb needs to be imaged by ultrasound if the CTPA
      is negative.

PMID- 17543007
TI  - The meaning of empowerment for nursing students: a critical incident study.
AB  - AIM: This paper is a report of a study to explore the meaning of empowerment for
      nursing students in relation to their clinical practice experiences. BACKGROUND:
      Empowerment and power are well-researched areas of nursing practice, particularly
      in relation to Registered Nurses. Furthermore, several studies have considered
      the experiences of nursing students in terms of nursing culture and
      socialization. However, few researchers have focused specifically on nursing
      student empowerment. METHOD: The critical incident technique was used and
      anonymous data were collected between November 2005 and January 2006. One hundred
      and nine written critical incidents were provided by 66 nursing students relating
      to empowering and disempowering experiences in clinical practice. The data were
      content analysed. FINDINGS: Nursing students experience both empowerment and
      disempowerment in clinical placements, centring on three issues: learning in
      practice, team membership and power. Continuity of placement, the presence of a
      mentor and time underpinned empowering experiences whereas their absence had a
      disempowering effect. CONCLUSION: The consequences of nursing student empowerment
      are high self-esteem, motivation for learning and positive regard for placement.
      Supportive mentors play a pivotal role in the empowerment of nursing students and
      it is essential for the nursing profession that they are supported to undertake
      their mentorship role.

PMID- 17543008
TI  - Theoretical perspectives of perceived control in older adults: a selective review
      of the literature.
AB  - AIM: This paper is a report of a theoretically based review of literature
      exploring the concept of perceived control in relation to older adults.
      BACKGROUND: Perceived control is a cognitive attribute that is a precursor to
      function, a mediator between social support and psychological wellbeing, and
      instrumental for effective disease self-management. It has been defined from
      several theoretical perspectives with either a global or a specific focus.
      METHODS: A review of literature was conducted. Articles were abstracted into a
      table in order to compare the purpose, theoretical framework, definition of
      perceived control, scope of application of perceived control, research questions,
      subjects, methods, instruments and findings across studies. The articles were
      sorted by theoretical framework for analyses among and between theoretical
      frameworks. RESULTS: Twenty papers published between 1995 and 2005, listed in
      CINAHL or Medline, with the words 'perceived control' in the title, and which
      included older adults as at least half of the sample and used one of five
      predominant theoretical frameworks were included in a review of the literature.
      In this review, perceived control is defined within the theories of social
      learning, self-efficacy, planned behaviour, the lifespan theory of control, and
      from a person-environment framework. There is little consensus among researchers
      as to the definition of perceived control. CONCLUSION: Lack of consensus on the
      theoretical underpinnings and variability in definition of perceived control
      exist. The mechanisms through which perceived control develops and is exercised
      are also in dispute. Nevertheless, there is general agreement that high perceived
      control is important for wellbeing in older adults.

PMID- 17543009
TI  - Towards a conceptual evaluation of transience in relation to palliative care.
AB  - AIM: This paper is a report of a concept evaluation of transience and its
      relevance to palliative care. BACKGROUND: A qualitative study into palliative
      care patients' experiences of transition revealed a gap between current
      definitions of transition and their expression of the palliative care experience.
      Transience appears to offer a better definition but remains conceptually weak,
      with limited definition in a healthcare context. METHODS: A qualitative
      conceptual evaluation of transience was undertaken using two case examples,
      interview data and the literature. Multiple sources were used to identify the
      literature (1966-2006), including a search on Cumulative Index to Nursing and
      Allied Health Literature Medline, and Ovid and Arts and Humanities Index using
      the keywords 'transience' and 'palliative care'. Thirty-one papers related to
      transience were retrieved. Analysis and synthesis formulated a theoretical
      definition of transience relative to palliative care. FINDINGS: Transience is a
      nascent concept. Preconditions and outcomes of transience appear contextually
      dependent, which may inhibit its conceptual development. Transience depicts a
      fragile emotional state related to sudden change and uncertainty at end-of-life,
      exhibited as a feeling of stasis. Defining attributes would seem to include
      fragility, suddenness, powerlessness, impermanence, time, space, uncertainty,
      separation and homelessness. CONCLUSIONS: Transience is potentially more
      meaningful for palliative care in understanding the impact of end-of-life
      experiences for patients than current conceptualizations of transition as a
      process towards resolution. As a nascent concept, it remains strongly
      encapsulated within a framework of transition and further conceptual development
      is needed to enhance its maturity and refinement.

PMID- 17543010
TI  - STAMP: components of observable behaviour that indicate potential for patient
      violence in emergency departments.
AB  - AIM: This paper is the report of a study to explicate the components of
      observable behaviour that indicate a potential for violence in patients, their
      family and friends when presenting at an emergency department. BACKGROUND:
      Violence towards nurses is a contemporary, multifaceted problem for the
      healthcare workforce globally. International literature identifies emergency
      departments as having high levels of violence. METHOD: A mixed method case study
      design was adopted, and data were collected by means of 290 hours of participant
      observation, 16 semi-structured interviews and 13 informal field interviews over
      a 5-month period in 2005. Thematic analysis of textual data was undertaken using
      NVivo2. Frequency counts were developed from the numerical data. FINDINGS: Five
      distinctive elements of observable behaviour indicating potential for violence in
      patients, their families and friends were identified. These elements can be
      conceptualized as a potential nursing violence assessment framework and described
      through the acronym STAMP: Staring and eye contact, Tone and volume of voice,
      Anxiety, Mumbling and Pacing. CONCLUSION: Staring and eye contact, Tone and
      volume of voice, Anxiety, Mumbling and Pacing provides a useful, practical
      nursing violence assessment framework to assist nurses to quickly identify
      patients, families and friends who have a potential for violence.

PMID- 17543011
TI  - In or out? Methodological considerations for including and excluding findings
      from a meta-analysis of predictors of antiretroviral adherence in HIV-positive
      women.
AB  - AIM: This paper is a discussion detailing the decisions concerning whether to
      include or exclude findings from a meta-analysis of report of quantitative
      studies of antiretroviral adherence in HIV-positive women. BACKGROUND:
      Publication constraints and the absence of reflexivity as a criterion for
      validity in, and reporting of, quantitative research preclude detailing the many
      judgements made in the course of a meta-analysis. Yet, such an accounting would
      assist researchers better to address the unique challenges to meta-analysis
      presented by the bodies of research they have targeted for review, and to show
      the subjectivity, albeit disciplined, that characterizes the meta-analytic
      process. DATA SOURCES: Data were 29 published and unpublished studies on
      antiretroviral adherence in HIV-positive women of any race/ethnicity, class, or
      nationality living in the United States of America. The studies were retrieved
      between June 2005 and January 2006 using 40 databases. REVIEW METHODS: Findings
      were included if they met the statistical assumptions of meta-analysis,
      including: (1) normal distribution of observations; (2) homogeneity of variances;
      and (3) independence of observations. RESULTS: Relevant studies and findings were
      excluded because of issues related to differences in study design, different
      operationalizations of dependent and independent variables, multiple cuts from
      common longitudinal data sets, and presentation of unadjusted and adjusted
      findings. These reasons led to the exclusion of 73% of unadjusted relationships
      and 87% of adjusted relationships from our data set, leaving few findings to
      synthesize. CONCLUSION: Decisions made during research synthesis studies may
      result in more information losses than gains, thereby obliging researchers to
      find ways to preserve findings that are potentially valuable for practice.

PMID- 17543012
TI  - Evaluation of informed consent: a pilot study.
AB  - AIM: This paper is a report of a study to describe and analyse the use of
      informed consent in clinical research, from the point of view of voluntary adult
      research participants, in order to develop and test an interview schedule for the
      evaluation of informed consent. BACKGROUND: Informed consent is one of the
      central ethical research principles in healthcare research, but empirical
      research on this topic is still scarce. To evaluate and develop the ethical
      quality of scientific research, there is a need to explore the meaning and
      implications of informed consent for research participants. METHOD: The data were
      collected in 2004 by interviews using an interview schedule created for this
      study by the first author and discussed in a multidisciplinary group. The
      response rate was 81%. The sample consisted of 32 patients with a metabolic
      syndrome who were participants in a project evaluating the effects of betaine on
      cardiovascular risk factors. FINDINGS: Participants stated that the key elements
      of informed consent are information, understanding and decision-making, and that
      competence is an essential factor in the reception and understanding of
      information and making an independent decision about participation. Our interview
      schedule was found to be useful in the investigation of informed consent.
      CONCLUSION: This study strengthened the perception that more extensive research
      about research participants is needed.

PMID- 17543013
TI  - Diaries as research data in a study on family caregivers of people with
      Alzheimer's disease: methodological issues.
AB  - AIM: This paper is a discussion of the use of unstructured diaries and their
      benefits and limitations as primary research data in a study of family caregivers
      of people with Alzheimer's disease. BACKGROUND: Caregivers' diaries have rarely
      been used to study family caregivers' subjective knowledge of life with a family
      member with Alzheimer's disease. METHOD: Family caregivers wrote unstructured
      diaries for 2 weeks during the period 2002-2004, starting within 6 months after
      the diagnosis of Alzheimer's disease in a family member. The family caregivers (n
      = 83) were voluntary participants in an ongoing intervention study (patients n =
      241 and caregivers n = 241). The diaries were analysed using content analysis.
      FINDINGS: The diary data were categorized into the following four different
      types: meagre, reporting, descriptive and reflective. They described the family
      caregivers' experiential world and the changes taking place in it. Family
      caregivers found diary-writing a therapeutic and pleasant experience. The use of
      written diaries involves some limitations concerning high dependency on writers,
      and data solely in written form. An effort to confirm the quality of data should
      be made by personal contacts. CONCLUSION: Diaries can be used as a primary method
      of data collection in nursing research, as they produce subjective knowledge of
      the experiences, emotions and meanings associated with caregiving. Their use can
      result in a high level of motivation, and ability to reflect on life promotes
      successful writing.

PMID- 17543014
TI  - Emergency department equipment for obese patients: perceptions of adequacy.
AB  - AIM: This study reports an investigation to assess patients' and nurses'
      perceptions of equipment adequacy for obese patients presenting at an emergency
      department and to assess nurses' knowledge of equipment weight limits in the
      emergency department. BACKGROUND: The increasing weight of populations in many
      societies is a challenge to healthcare providers and facilities. Emergency
      department equipment, specifically, may be inadequate for patient care. METHODS:
      Two questionnaires were developed. One was administered to 134 emergency
      department patients with suspected cardiac ischaemia; the other was administered
      to their respective nurses. Patient and nurse equipment adequacy scores were
      computed. Patients' self-reported height and weight were used to calculate body
      mass index. Waist circumference was measured. The data were collected in Canada
      in 2005. FINDINGS: Patient equipment adequacy scores correlated inversely with
      both body mass index (r = -0.55, 95% CI = -0.70 to -0.41, P < 0.01) and waist
      circumference (r = -0.62, 95% CI = -0.75 to -0.48, P < 0.01). Nurse equipment
      adequacy scores were also inversely related to patient body mass index (r = 
      0.34, 95% CI = -0.50 to -0.18, P < 0.01) and waist circumference (r = -0.40, 95%
      CI = -0.56 to -0.24, P < 0.01). There was a weak correlation between nurse and
      patient equipment adequacy scores (r = 0.27, 95% CI = -0.44 to -0.10, P < 0.01).
      Small minorities of nurses reported accurate knowledge of weight limits for beds,
      commodes and toilets. CONCLUSION: Specialized equipment and staff education are
      needed for adequate management of obese patients in the emergency department.

PMID- 17543015
TI  - An unusual pattern of atrioventricular block.

PMID- 17543017
TI  - Metabolic epidermal necrosis in a dog associated with pancreatic adenocarcinoma,
      hyperglucagonaemia, hyperinsulinaemia and hypoaminoacidaemia.
AB  - A case of metabolic epidermal necrosis associated with a pancreatic carcinoma is
      described. Normoglycaemia, reduced serum fructosamine, and hypoaminoacidaemia
      were identified. Hyperinsulinaemia and hyperglucagonaemia were documented.
      Immunohistochemistry documented strong tumour expression of both insulin and
      glucagon supporting combined paraneoplastic production of both hormones by the
      tumour. Enteral protein and fatty acid supplementation and parenteral amino acid
      supplementation proved ineffective. Metastasis to regional lymph nodes was
      identified and the patient was euthanased.

PMID- 17543016
TI  - Characterization and distribution of hyaluronan and the proteoglycans decorin,
      biglycan and perlecan in the developing embryonic mouse gonad.
AB  - The morphogenesis of tissues and organs requires dynamic changes in cells and in
      extracellular matrix components. It is known that various extracellular matrix
      molecules are of fundamental importance for gonad differentiation and growth. In
      the adult testis, the extracellular matrix represents an important component of
      the interstitium, participating in the transport of biologically active
      substances needed for the communication between different cellular components, as
      well as for the regulation of spermatogenesis and hormone production. The present
      study was designed in order to identify the proteoglycans biglycan, decorin and
      perlecan, as well as the glycosaminoglycan hyaluronan, during testis development
      in mouse embryos. Our data profile the chronology of testis differentiation, as
      well as the distribution of these extracellular matrix components during testis
      development in mice. We show that these extracellular matrix molecules are
      present early in the development of the gonads, suggesting that they play a role
      in gonad development. In addition, we found no decorin in the testicular cords.
      Furthermore, of the proteoglycans analysed, only biglycan was seen surrounding
      immature Sertoli cells and Leydig cell precursors in the testicular cords. This
      indicates that specific sets of extracellular matrix molecules are required in
      the various compartments of the developing gonad.

PMID- 17543018
TI  - Comparison of recovery times and complication rates between a modified slanted
      slot and the standard ventral slot for the treatment of cervical disc disease in
      20 dogs.
AB  - OBJECTIVES: To compare the recovery times and complication rates between the
      standard ventral slot and the modified slanted ventral slot for the treatment of
      cervical disc disease in dogs with the same neurological grade. METHODS: A
      retrospective analysis of an equal number of cervical disc cases for each
      procedure was carried out specifically to determine the recovery times and
      complication rates. To allow for meaningful comparison only dogs that had the
      same neurological grade were selected. Outcomes were determined by time to
      recover and the resolution of symptoms and complications were graded in terms of
      severity. RESULTS: The standard ventral slot cases had a higher complication rate
      than the modified slanted slot cases with one case dying in the postoperative
      period. However, the modified slanted slot cases on average had a marginally
      slower recovery time than standard ventral slot cases. CLINICAL SIGNIFICANCE:
      Ventral decompression using the modified slanted slot instead of the standard
      ventral slot will allow for spinal decompression with potentially less
      destabilisation, and incur a similar incidence of complications and rate of
      recovery.

PMID- 17543019
TI  - Intracranial empyema: literature review and two novel cases in cats.
AB  - OBJECTIVES: To review the literature on intracranial empyema and report two new
      cases in cats. METHODS: Literature review and case reports. RESULTS: Intracranial
      empyema has been rarely reported in small animals. In two novel cases in cats,
      the route of infection was postulated to be local extension from a retrobulbar
      abscess of odontogenic origin in one case and direct inoculation from a
      penetrating bite wound to the skull, confirmed at post-mortem examination, in the
      other. On magnetic resonance imaging of the first case, there was a contrast
      enhancing large extra-axial fluid collection overlying the right cerebral
      hemisphere, consistent with subdural empyema. Infection was caused by an
      Actinomyces spp. This is the first report of successful treatment of intracranial
      empyema by craniotomy, drainage and antibiotics. CLINICAL SIGNIFICANCE:
      Intracranial empyema is a neurosurgical emergency. Favourable outcomes may be
      achieved with surgical decompression, antimicrobial therapy and intensive care.

PMID- 17543020
TI  - Magnetic resonance imaging findings of neuroaxonal dystrophy in a papillon puppy.
AB  - A 3.5-month-old papillon puppy was brought to our clinic with chief complaints of
      progressive quadriparesis, ataxia and head tremor. Lesions in the cerebellum,
      brainstem and spinal cord were suspected on the basis of a neurological
      examination. No abnormality was found in a clinicopathological examination or on
      magnetic resonance imaging. On the basis of these results differential diagnoses
      including an inflammatory disease, a degenerative condition or a storage disorder
      were considered. Subsequently, the signs progressed and glossoplegia and
      dysphagia developed at six months of age. At a second magnetic resonance imaging,
      severe atrophy of the entire brain was found. After these examinations, the puppy
      was euthanased and histopathologically diagnosed with neuroaxonal dystrophy.
      Because magnetic resonance imaging detected abnormal features that were
      characteristic of neuroaxonal dystrophy in this case, we speculate that magnetic
      resonance imaging can assist in the pre-mortem diagnosis of this disease.

PMID- 17543021
TI  - Ulnocarpal arthrodesis in a cat.
AB  - A nine-year-old cat was presented with non-weight-bearing lameness of the right
      forelimb subsequent to an old fracture of the antebrachium previously treated by
      external stabilisation. Radiography showed severe atrophic non-union of the
      distal third of the radius and carpal luxation. Ulnocarpal arthrodesis was
      performed using a uniplanar external fixator. Follow-up radiography showed that
      bone fusion was slow but without complication. After 16 weeks, the external
      fixator was removed, and a Robert-Jones bandage was applied for one month. From
      postoperative week 2 onwards, the animal progressively made use of the limb in a
      weight-bearing capacity. At the last examination, one year postoperative, no
      lameness was observed.

PMID- 17543022
TI  - Central corneal dermoid in a Labrador retriever puppy.
AB  - An eight-week-old, male Labrador retriever puppy was presented with an abnormal
      appearance of the left cornea, observed after the eyelids opened in the second
      week of life. Ocular examination showed a large central dermoid of the left
      cornea. The dermoid was excised by superficial keratectomy, and healing was
      uneventful. The dermoid was classified as a Mann's second type. To the authors'
      knowledge, a Mann's second type corneal dermoid has not previously been reported
      in a dog.

PMID- 17543023
TI  - Comparison of methods for determining platelet numbers and volume in Cavalier
      King Charles spaniels.
AB  - OBJECTIVE: The purpose of this study was to compare platelet concentration in
      cavalier King Charles spaniels (CKCS) measured by different methods commonly used
      in veterinary hospitals and commercial laboratories. METHODS: Blood samples
      obtained from 41 CKCS [corrected] were analysed by impedance cell counter, laser
      cell counter and microscopic estimation. Quantitative buffy coat analysis was
      performed only on 17 samples, selected from CKCS [corrected] that had low
      platelet counts detected by cell counters. Platelet counts, platelet estimations
      and platelet parameters using these different methods were compared. RESULTS: The
      median platelet number was lower when estimated using impedance cell counter
      (1363x10(9)/I) with respect to laser cell counter (1723x10(9)/I), microscopic
      estimation (238x10(9)/I) [corrected] or quantitative buffy coat analyser
      (292x10(9)/I) [corrected] (P<0.01). Although impedance cell counter, laser cell
      counter and microscopic estimation were positively correlated, there was no
      acceptable agreement among methods. CKCS [corrected] with macrothrombocytes in
      blood smears had significantly lower counts on impedance cell counter, laser cell
      counter and microscopic estimation. The percentages of CKCS [corrected] with
      platelet count < 100x10(9)/I [corrected] were 34.1 per cent (impedance cell
      counter), 26.8 per cent (laser cell counter), 22.0 per cent (microscopic
      estimation) (not statistically different) and 5.8 per cent (quantitative buffy
      coat analyser) (P<0.05). CLINICAL SIGNIFICANCE: CKCS [corrected] with
      macrothrombocytosis have low platelet counts on impedance cell counters, laser
      cell counters and microscopic estimation. CKCS [corrected] with low platelet
      counts may have a normal platelet crit detected by a quantitative buffy coat
      analyser and thus a normal circulating platelet mass.

PMID- 17543024
TI  - Psychosocial and behavioural factors in heart transplant candidates--an overview.
AB  - Mortality among heart transplant (HTX) candidates remains high. This review of
      the literature shows that psychosocial characteristics like depression, social
      isolation and coping strategies contribute to morbidity and mortality in heart
      failure (HF) patients, and may also be relevant to the prognosis of HTX
      candidates. Based on the research to date, physical activity favourably affects
      subjective and objective parameters not only in HF patients, but also in HTX
      candidates. Depression is prevalent among HTX candidates, especially in ischaemic
      patients, and seems to be related to earlier transplantation. Findings on the
      effects of depression on pretransplant mortality are conflicting. Not much is
      known concerning social isolation, coping, nutrition, or weight loss in this
      patient group. Identification of modifiable psychosocial and behavioural
      variables related to clinical status in this patient group is clearly needed and
      will aid the development of behavioural interventions to supplement medical
      therapies.

PMID- 17543025
TI  - Autologous endothelial progenitor cells transplantation promoting endothelial
      recovery in mice.
AB  - Transplantation of endothelial progenitor cells (EPCs) restores endothelial
      function. The present study was designed to determine the effect of autologous
      EPCs transplantation on the regeneration of endothelium in mice. Mice splenectomy
      was performed 14 days before carotid artery injury, and mononuclear cells were
      isolated and cultured in endothelial growth media for 7 days. EPCs were confirmed
      by immunostaining (CD31, endothelial nitric oxide synthase (eNOS) and double
      positive for 1,1'dioctadecyl-3,3,3',3-tetramethylindocarbocyanine (DiI)-low
      density lipoprotein and ulex europaeus agglutinin (UEA)). Cell counts and
      fluorescence-activated cell sorting for stem cell marker were performed. 1 x
      10(6) 4-,6-Diamidino-2-phenylindole- labeled EPCs or saline were injected through
      tail vein after wire injury. Two weeks after transplantation, cell tracking and
      immunohistochemical staining showed homing and incorporation of labeled EPCs in
      injury artery. Administration of EPCs enhanced reendothelialization (P < 0.05)
      after 1 week and inhibition of neointima formation at 3 weeks compared with that
      of saline (P < 0.05, n = 6). These data demonstrate that delivery of autologous
      EPCs is associated with accelerated reendothelialization and reduced neointimal
      formation. Thus, delivery of autologous EPCs represents an important
      vasculoprotective approach to attenuate the response to acute vascular injury.

PMID- 17543030
TI  - Abnormal cellular energy and phospholipid metabolism in the left dorsolateral
      prefrontal cortex of medication-free individuals with bipolar disorder: an in
      vivo 1H MRS study.
AB  - OBJECTIVES: While the pathophysiology of bipolar disorder (BD) remains to be
      elucidated, postmortem and neuroimaging studies have suggested that abnormalities
      in the dorsolateral prefrontal cortex (DLPFC) are implicated. We compared the
      levels of specific brain chemicals of interest measured with proton magnetic
      resonance spectroscopy ((1)H MRS) in medication-free BD subjects and age- and
      gender-matched healthy controls. We hypothesized that BD subjects would present
      abnormal cellular metabolism within the DLPFC, as reflected by lower N-acetyl
      aspartate (NAA) and creatine + phosphocreatine (Cr + PCr). METHODS: Thirty-two
      medication-free BD subjects (33.8 +/- 10.2 years) and 32 matched controls (33.8
      +/- 9.0 years) underwent a short echo-time (TE = 30 ms) (1)H MRS. An 8-cm(3)
      single voxel was placed in the left DLPFC, and individual concentrations of NAA,
      Cr + PCr, choline-containing compounds (GPC + PC), myo-inositol, and glutamate
      were obtained, using the water signal as an internal reference. RESULTS: BD
      subjects had lower Cr + PCr [F((1,62)) = 5.85; p = 0.018; one-way analysis of
      variance (ANOVA)] and lower GPC + PC [F((1,62)) = 5.79; p = 0.019; one-way ANOVA]
      levels in the left DLPFC. No significant differences were observed for other
      brain metabolites. CONCLUSIONS: These findings provide further evidence that the
      pathophysiology of BD involves impairment in the DLPFC. Our findings can be
      interpreted as evidence for reduced cellular energy and phospholipid metabolism,
      consistent with the hypothesis of mitochondrial dysfunction in BD.

PMID- 17543031
TI  - Traumatic life events in bipolar disorder: impact on BDNF levels and
      psychopathology.
AB  - BACKGROUND: There is evidence that vulnerability to depression and anxiety
      disorders is markedly increased by traumatic life events. While childhood abuse
      has been reported to be associated with poorer outcomes in bipolar disorder,
      little is known about the neurobiological basis underlying this association. The
      aim of this study was to ascertain whether bipolar patients who were exposed to a
      traumatic event or events (TE) have lower brain-derived neurotrophic factor
      (BDNF) levels and more severe psychopathology as indicated by increased
      comorbidity and other clinical features when compared to those who were not
      exposed to TE. METHODS: One-hundred and sixty-three consecutively recruited
      bipolar outpatients were assessed by Structured Clinical Interview for DSM-IV
      (SCID) and standard protocol in order to evaluation psychopathology and clinical
      features. The reported TE was assessed using DSM-IV stem criteria for trauma (as
      defined by A1 and A2 criteria for trauma for post-traumatic stress disorder).
      Subjects were divided into 2 groups according to presence or absence of lifetime
      TE. The levels of BDNF, comorbidity and other clinical features were compared
      between groups. RESULTS: After adjusting for confounders, results indicated that
      bipolar patients with a history of TE have alcohol abuse/dependence (p < 0.001),
      anxiety comorbidity, and lower levels of serum BDNF (p < 0.01) compared to those
      without a history of TE. There was no difference between the 2 groups in age of
      onset, presence of psychosis, other substance abuse and dependence, rapid cycling
      or suicide attempts. CONCLUSIONS: Our findings suggest that TE are associated
      with significantly increased prevalence of alcohol and anxiety comorbidity as
      well as lower BDNF levels in bipolar patients. It is possible that a decrease in
      BDNF levels may account for increased comorbidity, but further prospective
      studies are required to confirm this.

PMID- 17543032
TI  - Impaired verbal memory and otherwise spared cognition in remitted bipolar
      patients on monotherapy with lithium or valproate.
AB  - OBJECTIVES: Patients with bipolar disorder have been reported to have
      neurocognitive deficits; however, it is not known whether the cognitive
      dysfunctions are state-dependent or a stable trait. Lithium and valproate, 2 of
      the most widely used mood stabilizers in the treatment of bipolar disorder, have
      also been associated with cognitive impairment. However, the degree and pattern
      of neurocognitive impairment in euthymic bipolar patients on either monotherapy
      with lithium or valproate have not been compared before in depth. METHODS: We
      compared 17 euthymic outpatients with bipolar disorder (BD) on lithium
      monotherapy to 11 euthymic outpatients with BD on valproate monotherapy and 29
      comparison subjects using tests measuring immediate verbal memory and executive
      functions in addition to 3 subtests of the Wechsler Adult Intelligence Scale
      Revised. The groups were similar in terms of level of education, duration and
      severity of illness, and gender distribution. Patients on lithium monotherapy
      were older than patients on valproate and healthy controls. Mood symptoms as
      assessed by standardized scales were mild to non-existent in both patient groups.
      RESULTS: Immediate verbal memory was impaired in both patient groups compared to
      controls, where the main effect of age was not significant. No significant
      differences could be found on the other cognitive measures. CONCLUSIONS: Both
      lithium and valproate may be associated with immediate verbal memory impairment,
      sparing other cognitive functions. Presence of a similar verbal memory deficit in
      the lithium and valproate groups suggests that this deficit might be intrinsic to
      BD or that the 2 medications influence immediate verbal memory similarly. Larger
      samples of remitted bipolar patients on monotherapy should be studied for more
      precise conclusions.

PMID- 17543033
TI  - Evidence for disruption in prefrontal cortical functions in juvenile bipolar
      disorder.
AB  - OBJECTIVES: Systematic parsing of executive function processes is critical for
      the development of more specific models of neurobiological processes mediating
      disturbed cognition in youth with bipolar disorder (BPD). METHODS: A sample of 33
      children and adolescents with bipolar I disorder (BPD I) (mean age 12.1 +/- 3.0
      years, 39% female) and 44 demographically matched healthy participants (mean age
      12.9 +/- 2.8 years, 50% female) completed a neurocognitive battery including
      measures aimed at detection of disruption in prefrontal cortical circuitry (i.e.,
      working memory, set shifting, and rule attainment). RESULTS: Compared to healthy
      controls, BPD I children exhibited significant deficits in spatial working
      memory, visual sequencing and scanning, verbal fluency and abstract problem
      solving, particularly when a memory component was involved. In our spatial
      delayed response task, memory set size was parametrically varied; the performance
      pattern in BPD I children suggested deficits in short-term memory encoding and/or
      storage, rather than capacity limitations in spatial working memory. Earlier age
      at onset of illness and antipsychotic medication usage were associated with
      poorer performance on speeded information-processing tasks; however, severity of
      mood symptomatology and comorbidity with disruptive behavior disorders were not
      associated with task performance. CONCLUSIONS: These results suggest impairment
      in measures of prefrontal cortical function in juvenile BPD I that are similar to
      those seen in the adult form of the illness, and implicate both the ventral and
      dorsolateral prefrontal cortex as loci of pathology in juvenile BPD. As these
      deficits were not associated with clinical state or comorbidity with other
      disorders, they may reflect trait-related impairments, a hypothesis that will be
      pursued further in longitudinal studies.

PMID- 17543035
TI  - Candidate genes for panic disorder: insight from human and mouse genetic studies.
AB  - Panic disorder is a major cause of medical attention with substantial social and
      health service cost. Based on pharmacological studies, research on its
      etiopathogenesis has been focused on the possible dysfunction of specific
      neurotransmitter systems. However, recent work has related the genes involved in
      development, synaptic plasticity and synaptic remodeling to anxiety disorders.
      This implies that learning processes and changes in perception, interpretation
      and behavioral responses to environmental stimuli are essential for development
      of complex anxiety responses secondary to the building of specific brain neural
      circuits and to adult plasticity. The focus of this review is on progress
      achieved in identifying genes that confer increased risk for panic disorder
      through genetic epidemiology and the use of genetically modified mouse models.
      The integration of human and animal studies targeting behavioral, systems-level,
      cellular and molecular levels will most probably help identify new molecules with
      potential impact on the pathogenetic aspects of the disease.

PMID- 17543036
TI  - Activity-dependent changes of the hippocampal CA3-CA1 synapse during the
      acquisition of associative learning in conscious mice.
AB  - Contemporary neuroscientists are paying increasing attention to subcellular,
      molecular and electrophysiological mechanisms underlying learning and memory
      processes. Recent efforts have addressed the development of transgenic mice
      affected at different stages of the learning process, or emulating pathological
      conditions involving cognition and motor-learning capabilities. However, a
      parallel effort is needed to develop stimulating and recording techniques
      suitable for use in behaving mice, in order to grasp activity-dependent neural
      changes taking place during the very moment of the process. These in vivo models
      should integrate the fragmentary information collected by different molecular and
      in vitro approaches. In this regard, long-term potentiation (LTP) has been
      proposed as the neural mechanism underlying synaptic plasticity. Moreover, N
      methyl-d-aspartate (NMDA) receptors are accepted as the molecular substrate of
      LTP. It now seems necessary to study the relationship of both LTP and NMDA
      receptors with the plastic changes taking place, in selected neural structures,
      during actual learning. Here, we review data on the involvement of the
      hippocampal CA3-CA1 synapse in the acquisition of classically conditioned eyelid
      conditioned responses (CRs) in behaving mice. Available data show that LTP,
      evoked by high-frequency stimulation of Schaffer collaterals, disturbs both the
      acquisition of CRs and the physiological changes that occur at the CA3-CA1
      synapse during learning. Moreover, the administration of NMDA-receptor
      antagonists is able not only to prevent LTP induction in vivo, but also to hinder
      the formation of both CRs and functional changes in strength of the CA3-CA1
      synapse. Thus, there is experimental evidence relating activity-dependent
      synaptic changes taking place during actual learning with LTP mechanisms and with
      the role of NMDA receptors in both processes.

PMID- 17543037
TI  - The Rubinstein-Taybi syndrome: modeling mental impairment in the mouse.
AB  - Mental impairment syndromes are diagnosed based on below-average general
      intellectual function originated during developmental periods. Intellectual
      abilities rely on the capability of our brain to obtain, process, store and
      retrieve information. Advances in the past decade on the molecular basis of
      memory have led to a better understanding of how a normal brain works but also
      have shed new light on our understanding of many pathologies of the nervous
      system, including diverse syndromes involving mental impairment. The recent
      multidisciplinary analysis of various mouse models for Rubinstein-Taybi syndrome
      has shown the power of animal models to produce an important leap forward in our
      understanding of a complex mental disease while simultaneously opening new
      avenues for its treatment. These studies also suggest that some of the cognitive
      and physiological deficits observed in mental impairment syndromes may not simply
      be caused by defects originated during development but may result from the
      continued requirement of specific enzymatic activities throughout life.

PMID- 17543038
TI  - Thyroid hormones, learning and memory.
AB  - Thyroid hormones (THs), T3 and T4, have many physiological actions and are
      essential for normal behavioral, intellectual and neurological development. THs
      have a broad spectrum of effects on the developing brain and mediate important
      effects within the CNS throughout life. Insufficient maternal iodine intake
      during gestation and TH deficiency during human development are associated to
      pathological alterations such as cretinism and mental retardation. In adulthood,
      thyroid dysfunction is related to neurological and behavioral abnormalities,
      including memory impairment. Analysis of different experimental models suggests
      that most of the effects on cognition as a result of thyroid dysfunction rely on
      hippocampal modifications. Insufficiency of THs during development thus alters
      hippocampal synaptic function and impairs behavioral performance of hippocampal
      dependent learning and memory tasks that persist in euthyroid adult animals. In
      the present review, we summarize the current knowledge obtained by clinical
      observations and experimental models that shows the importance of THs in learning
      and mnemonic processes.

PMID- 17543039
TI  - Developmental mechanisms and experimental models to understand forebrain
      malformative diseases.
AB  - The development of the central nervous system can be divided into a number of
      phases, each of which can be subject of genetic or epigenetic alterations that
      may originate particular developmental disorders. In recent years, much progress
      has been made in elucidating the molecular and cellular mechanisms by which the
      vertebrate forebrain develops. Therefore, our understanding of major
      developmental brain disorders such as cortical malformations and neuronal
      migration disorders has significantly increased. In this review, we will describe
      the major stages in forebrain morphogenesis and regionalization, with special
      emphasis on developmental molecular mechanisms derailing telencephalic
      development with subsequent damage to cortical function. Because animal models,
      mainly mouse, have been fundamental for this progress, we will also describe some
      characteristic mouse models that have been capital to explore these molecular
      mechanisms of malformative diseases of the human brain. Although most of the
      genes involved in the regulation of basic developmental processes are conserved
      among vertebrates, the extrapolation of mouse data to corresponding gene
      expression and function in humans needs careful individual analysis in each
      functional system.

PMID- 17543040
TI  - Evolution or revolution? Adapting to complexity in wound management.
AB  - Wound clinics are seeing an increase in the number of 'complex' wounds, which
      arise as the result of the interaction between multiple coexisting systemic
      pathologies, environmental factors and local wound factors. These complex wounds
      require an approach to diagnosis and management that can encapsulate all these
      factors. Unified wound assessment approaches such as HEIDI (History, Examination,
      Investigations, Diagnosis and management plan), wound bed preparation and applied
      wound management systems are essential to reach a definitive diagnosis and to
      ensure that management is agreed between the various clinical specialities that
      may be involved. A series of case histories is presented that illustrate the
      benefits of a unified approach to wound management. Results of a study into the
      cost-effectiveness of an improved foam dressing are presented, and the problems
      of demonstrating the ability to make long-term savings through short-term
      expenditure are discussed.

PMID- 17543041
TI  - Abstracts of the 30th Annual Meeting of the Research Society on Alcoholism. July
      7-11, 2007. Chicago, Illinois, USA.

PMID- 17543046
TI  - Australian Rheumatology Association in conjunction with Rheumatology Health
      Professionals Association 49th Annual Scientific Meeting, 26-30 May 2007, Sydney,
      Australia.

PMID- 17543052
TI  - Understanding the role of genetics in disability insurance.

PMID- 17543053
TI  - Genetic testing and the future of disability insurance: ethics, law & policy.
AB  - Predictive genetic testing poses fundamental questions for disability insurance,
      a crucial resource funding basic needs when disability prevents income from work.
      This article, from an NIH-funded project, presents the first indepth analysis of
      the challenging issues: Should disability insurers be permitted to consider
      genetics and exclude predicted disability? May disabilities with a recognized
      genetic basis be excluded from coverage as pre-existing conditions? How can we
      assure that private insurers writing individual and group policies, employers,
      and public insurers deal competently and appropriately with genetic testing?

PMID- 17543054
TI  - Genetic testing and disability insurance: an alternative opinion.
AB  - As members of the Working Group on Genetic Testing in Disability Insurance, the
      authors of this alternative opinion describe their areas of disagreement with
      some of the conclusions in the paper written by Susan M. Wolf and Jeffrey P.
      Kahn.

PMID- 17543055
TI  - Predictive medical information and underwriting.
AB  - Medical underwriting involves the application of actuarial science by analyzing
      medical information to predict the future risk of a claim. The objective is that
      individuals with like risk are treated in a like manner so that the premium paid
      is proportional to the risk of future claim.

PMID- 17543056
TI  - Disability income insurance: the private market and the impact of genetic
      testing.
AB  - This article discusses the disability insurance industry in order to provide
      context regarding the potential impact of genetic testing on disability
      insurance. It describes disability income insurance, exploring both the
      protection it offers and its main contract provisions. It goes on to describe the
      private insurance market and the differences between group and individual
      insurance, and concludes with implications of genetic testing with respect to the
      private disability insurance market.

PMID- 17543057
TI  - Genetic testing and the future of disability insurance: thinking about
      discrimination in the genetic age.
AB  - This article considers the future of genetic testing and disiblity insurance, and
      explores the potential for discrimination when using genetic information.

PMID- 17543058
TI  - Predictive genetic testing: congruence of disability insurers' interests with the
      public interest.
AB  - This article argues that, under existing jurisprudence, the disability insurance
      business will be harmed, not benefited, from broad access to the results of
      genetic testing identifying people with higher than species-typical genetic
      propensities for illness.

PMID- 17543059
TI  - Genetic exceptionalism and legislative pragmatism.
AB  - Genetic-specific nondiscrimination laws have been enacted in most states, but the
      laws are ineffective and increase the stigma of genetic conditions. Whether these
      laws are better than no new legislation depends on their consequences and a
      recognition of their limitations.

PMID- 17543060
TI  - Genetic screening and disability insurance: what can we learn from the health
      insurance experience?
AB  - Genetic information may be used by health and disability insurance companies to
      deny or restrict coverage. How health insurance companies use genetic
      information, and how public policy has limited that use, can be illustrative for
      genetics and disability insurance policy.

PMID- 17543061
TI  - Workers' Compensation, Social Security Disability, SSI, and Genetic Testing.
AB  - This article argues that the use of genetic testing to determine eligibility for
      worker compensation and/or social security disability benefits would seriously
      undermine the social purposes of the laws.

PMID- 17543063
TI  - Abstracts of the 5th European Congress on Tropical Medicine and International
      Health, 24-28 May 2007, Amsterdam, the Netherlands.

PMID- 17543062
TI  - Life, health, and disability insurance: understanding the relationships.
AB  - Communitarian values are stronger in health insurance than in life or disability
      insurance. This correlates with increased tolerance for insurers' use of genetic
      information in disability insurance underwriting, which, in turn, is relevant to
      the scope and content of proposals to regulate such use.

PMID- 17543066
TI  - Abstracts of the Annual Meeting of the European Academy of Childhood Disability.
      June 14-16, 2007. Groningen, The Netherlands.

PMID- 17543071
TI  - Haematopathology practice: the commonest problems encountered in a consultation
      practice.
AB  - Although not specifically recognized as a subspecialty of histopathology,
      haematopathology has a long history of specialist practice in the UK, with a few
      centres attracting large numbers of referred cases. The specialist nature of
      haematopathology has been enhanced by the advent of immunohistochemistry and,
      more recently, molecular genetics, which now play a major role in the diagnosis
      of haematopoietic and lymphoid neoplasms. Problems encountered by non-specialist
      pathologists, and reflected in those cases submitted for consultation, include
      difficulties in the differential diagnosis of certain benign lymphoproliferative
      disorders from lymphoma and the precise classification of lymphomas which may
      have an impact on therapeutic decisions. Lymphomas that frequently pose problems
      include common lesions such as follicular lymphoma and more esoteric disorders
      such as T-cell/histiocyte-rich large B-cell lymphoma. This review is an attempt
      to clarify a logical approach to the differential diagnosis of these lesions.

PMID- 17543072
TI  - Nuclear survivin is associated with disease recurrence and poor survival in
      patients with cutaneous malignant melanoma.
AB  - AIMS: Survivin is expressed in neoplastic cells and appears to be associated with
      resistance to therapy and shorter survival in various types of tumours. The aim
      of the present study was to determine whether nuclear or cytoplasmic expression
      of survivin is related to disease recurrence and overall survival of patients
      with Stage I and II melanoma according to the American Joint Committee on Cancer
      (AJCC) staging system. METHODS AND RESULTS: Immunohistochemistry was performed on
      formalin-fixed paraffin-embedded sections of primary cutaneous melanoma from 50
      patients. Survival rates were estimated using the Kaplan-Meier method and
      compared using the log rank test. Association of clinical variables (gender, age,
      tumour location, thickness, Clark level and AJCC stage) with survivin expression
      was analysed by Fisher's exact test. Patients with nuclear immunoreactivity for
      survivin had an increased risk of disease recurrence during the first three
      postoperative years (P < 0.05) and of death (P < 0.05). Cytoplasmic
      immunoreactivity was not correlated with either survival or clinical variables.
      CONCLUSIONS: Nuclear presence of survivin may be an independent biomarker for
      disease recurrence and overall survival in patients with Stage I and II melanoma.

PMID- 17543073
TI  - Gastric mucin is expressed in a subset of endocervical tunnel clusters: type A
      tunnel clusters of gastric phenotype.
AB  - AIMS: Gastric mucin expression has been demonstrated in a group of endocervical
      glandular lesions. The aim of this study was to gain further insight into
      endocervical lesions with a gastric phenotype. METHODS AND RESULTS: Various types
      of tunnel clusters (TC) were examined for gastric mucin by alcian blue/periodic
      acid-Schiff staining and immunohistochemistry for HIK1083. Five of 34 cases of TC
      expressed gastric mucin defined by PAS dominant neutral mucin and
      immunopositivity for pyloric gland mucin. Histologically, TC expressing gastric
      mucin showed lobular arrangements of small to medium-sized glands composed of
      mucin-rich columnar cells and were classified as Flumann's type A TC. Neither
      type B TC nor normal endocervical glands expressed PAS dominant neutral mucin and
      none of them was immunopositive for pyloric gland mucin. Five patients with type
      A TC of gastric phenotype ranged in age from 33 to 79 years (mean 58 years) and
      were multiparous. Type A TC of gastric phenotype, ranging from 2 to 4 mm in
      maximum diameter, were incidental findings in hysterectomy specimens. CONCLUSION:
      Type A TC of gastric phenotype could be related to lobular endocervical glandular
      hyperplasia of gastric phenotype. The pathogenesis of gastric metaplasia in TC
      remains unclear.

PMID- 17543074
TI  - Uterine leiomyosarcomas are characterized by high p16, p53 and MIB1 expression in
      comparison with usual leiomyomas, leiomyoma variants and smooth muscle tumours of
      uncertain malignant potential.
AB  - AIMS: It has been suggested that p16 is overexpressed in uterine leiomyosarcomas
      in comparison with leiomyomas. In this study, p16 immunohistochemical expression
      was assessed in a variety of uterine smooth muscle tumours, including usual
      leiomyomas, leiomyoma variants, smooth muscle tumours of uncertain malignant
      potential (STUMPs) and leiomyosarcomas. The aim was to ascertain whether there
      are differences in p16 expression between these groups and whether p16 is of
      potential value in the assessment of problematic uterine smooth muscle neoplasms.
      p16 expression was also compared with that of p53 and MIB1. METHODS AND RESULTS:
      Cases of usual leiomyoma (n = 10), leiomyoma variants (n = 27), STUMP (n = 4) and
      leiomyosarcoma (n = 22) were subject to p16, p53 and MIB1 immunohistochemistry.
      For p16, cases were evaluated with respect to both staining distribution and
      intensity. There was a statistically significant difference in p16 distribution
      (P < 0.001) and intensity (P = 0.001) between leiomyosarcomas and the other
      groups. There was no difference in p16 expression between usual leiomyomas,
      leiomyoma variants and STUMPs. There were also statistically significant
      differences in p53 (P = 0.014) and MIB1 (P < 0.001) immunoreactivity between
      leiomyosarcomas and the other groups. CONCLUSIONS: p16 is overexpressed in
      uterine leiomyosarcomas compared with leiomyomas, benign leiomyoma variants and
      STUMPs, suggesting that p16 may be implicated in the pathogenesis of malignant
      uterine smooth muscle neoplasms. p16, in combination with p53 and MIB1, may be of
      value as an adjunct to morphological examination in the assessment of problematic
      uterine smooth muscle tumours, although further large-scale studies with follow
      up are necessary to confirm this.

PMID- 17543075
TI  - Flat epithelial atypia (DIN 1a, atypical columnar change): an underdiagnosed
      entity very frequently coexisting with lobular neoplasia.
AB  - AIMS: Flat epithelial atypia of the breast [FEA; synonyms: ductal intraepithelial
      neoplasia (DIN) 1a, atypical columnar change] is increasingly recognized by
      pathologists and shows distinct genetic alterations. The aim of this study was to
      determine its biological significance as an incidental finding in breast biopsy
      specimens. METHODS AND RESULTS: On the assumption that both FEA and lobular
      neoplasia (LN) derive from progenitor cells in the terminal ductal-lobular unit,
      we investigated the association between FEA and LN semiquantitatively in 111
      excisional breast biopsy specimens which contained LN, but did not contain ductal
      carcinoma in situ (DCIS) or invasive carcinoma. Ninety-six cases (86.5%) revealed
      coexistence of LN and FEA (P < 0001). The distribution of LN was focal in 41
      cases (37%), multifocal in 50 (45%) and extensive in 20 (18%) cases. FEA was
      identified as focal, multifocal and extensive in 29 (26%), 42 (38%) and 25 (23%)
      cases, respectively. Distribution patterns of LN and FEA showed no statistically
      significant correlation. CONCLUSIONS: Due to the striking association between LN
      and FEA in our material, one may speculate that these two lesions are
      biologically related and that FEA is an early but non-obligate precursor lesion
      similar to LN. Based on this assumption, regular clinical and mammographic follow
      up of patients with FEA would be prudent.

PMID- 17543076
TI  - Expression of androgen receptor and two androgen-induced proteins (apolipoprotein
      D and pepsinogen C) in ductal carcinoma in situ of the breast.
AB  - AIMS: To evaluate the expression of androgen receptors (AR) and two androgen
      induced proteins [apolipoprotein D (ApoD) and pepsinogen C (PepC)] in ductal
      carcinoma in situ (DCIS) of the breast. METHODS AND RESULTS: AR, ApoD and PepC
      expression was examined in 28 cases of pure DCIS and in 31 cases of DCIS adjacent
      to invasive carcinoma of the breast using immunohistochemical methods and then
      correlated with the architectural subtype, the degree of differentiation and the
      ostrogen receptor (ER)/progesterone receptor (PgR)/HER-2 status. We found no
      significant differences between pure DCIS and DCIS adjacent to invasive breast
      cancer regarding the percentage of positive cases for ApoD (64.3% versus 54.8%),
      PepC (42.9% versus 48.4%), ER (64.3% versus 58.1%), PgR (60.7% versus 58.1%) and
      HER-2 (39.3% versus 67.7%). However, there was a significantly higher percentage
      of AR+ DCIS among those adjacent to invasive carcinomas of the breast than among
      pure DCIS lesions (93.5% versus 60.9%) (P = 0.009). AR expression did not
      correlate with architectural subtype, degree of differentiation, or ER/PgR/HER
      2/ApoD/PepC status, in cases of pure DCIS, nor in DCIS adjacent to invasive
      carcinoma of the breast. CONCLUSIONS: AR expression may represent an independent
      predictive factor in DCIS of the breast.

PMID- 17543077
TI  - Expression of ERalpha and ERbeta in lobular carcinoma in situ.
AB  - AIMS: Oestrogen is a modulator of cell growth and differentiation in the breast.
      It mediates most of its function through members of the oestrogen receptor (ER)
      family, ERalpha and ERbeta. Lobular carcinoma in situ (LCIS) is a known risk
      factor for the development of breast cancer; however, the use of tamoxifen for
      prevention is based upon data for ER+ (ERalpha) LCIS associated with invasion,
      but limited data exist on the use of tamoxifen in cases of ER+ (ERalpha) LCIS
      occurring in the absence of invasive carcinoma. The aim of this study was to
      examine ER expression in LCIS to determine the relationship of ERalpha to ERbeta
      and, thereby, to determine whether it is of clinical value to measure ERbeta
      along with ERalpha. METHODS AND RESULTS: Core biopsy specimens from 50 patients
      were examined retrospectively. Histology was reviewed and histological parameters
      were assessed. Formalin-fixed paraffin-embedded tissue was available for E
      cadherin, ERalpha and ERbeta immunohistochemistry. The degree of ERalpha and
      ERbeta nuclear reactivity was quantified. The patients' mean age was 55 years.
      The mean follow-up duration was 48 months. All 50 cases of LCIS were E-cadherin
      negative. All cases were ERalpha+ and ERbeta+. The staining intensity of ERbeta
      was strong and included staining of periductal stromal cells. The median
      percentage of cells immunoreactive for ERalpha was 75% and for ERbeta 70% (range
      10% weak positive to 100% strong positive). There was a statistically significant
      relationship between ERbeta staining intensity and incidence of ipsilateral
      breast cancer (P = 0.010). CONCLUSIONS: The presence and intensity of both
      stromal and glandular ERbeta immunoreactivity suggest that the action of
      oestrogen on LCIS is on both stromal and glandular cells. Future studies are
      needed to determine whether the presence of ERbeta in LCIS could be targeted to
      influence the treatment of this disease and perhaps alter its natural history.

PMID- 17543078
TI  - Detection of the ASPSCR1-TFE3 gene fusion in paraffin-embedded alveolar soft part
      sarcomas.
AB  - AIMS: Alveolar soft part sarcoma (ASPS) is a rare soft tissue tumour with unique
      morphology and a recurrent, non-reciprocal translocation
      der(17)t(X;17)(p11.2;q25) leading to the fusion of ASPSCR1 (also known as ASPL)
      to the transcription factor TFE3. Although diagnosis is straightforward in
      classical cases, tumours with atypical morphological features may be difficult to
      classify solely on the basis of conventional histopathology. The aim of this
      study was to analyse the chromosomal breakpoints in paraffin-embedded tissue.
      METHODS AND RESULTS: Three male and two female ASPS patients including one case
      with uncommon histology were investigated by fluorescence in situ hybridization
      with split- and fusion-probes. The presence of the resulting ASPSCR1-TFE3 fusion
      transcripts was assessed by reverse transcriptase-polymerase chain reaction.
      Hybridization results showed a t(X;17)(p11.2;q25) in all tumours with a
      duplication of the telomeric part of chromosome Xp. In addition to wild-type
      TFE3, ASPSCR1-TFE3 fusion transcripts (three type 1 and two type 2 transcripts)
      were detected in all cases. CONCLUSIONS: Molecular confirmation of ASPSCR1-TFE3
      gene fusion is applicable to routinely processed archival and diagnostic tumour
      samples and aids in the differential diagnosis of ASPS.

PMID- 17543079
TI  - Neuronal features of oligodendrogliomas--an ultrastructural and
      immunohistochemical study.
AB  - AIMS: To assess neuronal differentiation in oligodendrogliomas (ODGs). METHODS
      AND RESULTS: An electron microscopic and immunohistochemical study of 41
      consecutive cases was performed. In all cases, tumour cells with neuritic
      structures were identified ultrastructurally, including synapses and
      neurosecretory granules. For the immunohistochemical identification of
      synaptophysin, monoclonal antibody clones 27G12, Snp88 and SY38 and a polyclonal
      antibody were compared in optimized protocols on slides from a spectrum of
      tissues and 16 ODGs. 27G12 gave the best signal-to-noise ratio, while SY38 gave
      the poorest. When 27G12 was applied on all 41 ODGs, widespread immunoreactivity
      was obtained in 100%. Among three antibodies to chromogranin compared similarly,
      clone LK2H10 and a polyclonal antibody gave identical patterns of
      immunoreactivity, whereas clone DAK-A3 gave weaker reactions. When LK2H10 was
      applied on all tumours, staining was found in 12 (29%). All tumours but one
      stained strongly for glial fibrillary acidic protein and all for synapsin I.
      Fluorescence in situ hybridization analysis showed a concomitant 1p/19q deletion
      in 12/16 ODGs. CONCLUSIONS: Our study provides evidence for widespread neuronal
      differentiation in ODGs, suggesting that these tumours may be derived from
      progenitor cells with limited commitment. Antibody selection and protocol
      optimization are mandatory for reliable immunohistochemistry results.

PMID- 17543080
TI  - Reactive astrocytes and activated microglial cells express EAAT1, but not EAAT2,
      reflecting a neuroprotective potential following ischaemia.
AB  - AIMS: Glutamate receptor antagonists have failed clinical stroke trials and it
      has been proposed that the action of N-methyl D-aspartate receptors is necessary
      for neuronal survival. Thus, excitatory amino acid transporters (EAATs) might be
      a promising therapeutic target. The aim of this study was to investigate glial
      expression of EAATs following ischaemia. METHODS AND RESULTS: Expression of EAAT1
      (GLAST) and EAAT2 (Glt-1) in 24 cases of ischaemia was examined by
      immunohistochemistry. Cortical expression of both EAATs in the lesion decreased
      within 24 h (P < 0.01, each). Whereas EAAT1+ white matter cells increased 18-fold
      (P < 0.05) within 24 h in the lesion and remained elevated for months in adjacent
      (469-fold, P < 0.01) and remote areas (20-fold, P < 0.05), EAAT2+ white matter
      cells were equivalent in ischaemia and controls. In the first week after stroke
      mainly activated (ramified and amoeboid) microglia expressed EAAT1, whereas
      monocytic cells in perivascular spaces and foamy macrophages lacked EAAT1. After
      more than 1 week, predominantly reactive astrocytes expressed EAAT1. CONCLUSIONS:
      Microglial EAAT1 expression is restricted to the early/intermediate stage of
      activation and blood-derived (perivascular) monocytes do not contribute to EAAT1+
      cells following ischaemia. Whether a pharmacological increase in glial EAAT
      expression may compensate for loss of cortical EAAT expression and reduce
      neuronal damage following stroke requires investigation by further functional
      studies.

PMID- 17543081
TI  - Chromatin assembly factor-1 (CAF-1)-mediated regulation of cell proliferation and
      DNA repair: a link with the biological behaviour of squamous cell carcinoma of
      the tongue?
AB  - AIMS: Squamous cell carcinoma (SCC) of the tongue shows aggressive behaviour and
      a poor prognosis. Clinicopathological parameters fail to provide reliable
      prognostic information, so the search continues for new molecular markers for
      this tumour. Chromatin assembly factor-1 (CAF-1) plays a major role in chromatin
      assembly during cell replication and DNA repair and has been proposed as a new
      proliferation marker. The aim of this study was to investigate its expression in
      SCC of the tongue. METHODS AND RESULTS: The immunohistochemical expression of the
      p60 and p150 subunits of CAF-1 were evaluated in a series of SCCs of the tongue.
      The findings were correlated with the expression of proliferation cell nuclear
      antigen (PCNA) and patients' clinicopathological and follow-up data. CAF-1/p60
      was expressed in all the tumours, whereas CAF-1/p150 was down-regulated in a
      number of cases. Overexpression of CAF-1/p60 and down-regulation of CAF-1/p150
      identified SCCs with poor outcome, in addition to the classical prognostic
      parameters. CONCLUSIONS: Simultaneous CAF-1-mediated deregulation of cell
      proliferation and DNA repair takes place in aggressive SCC of the tongue.
      Therefore, the evaluation of CAF-1 expression may be a valuable tool for
      evaluation of the biological behaviour of these tumours. This may be relevant to
      the introduction of improved follow-up protocols and/or alternative therapeutic
      regimens.

PMID- 17543082
TI  - Grading of dysplasia in Barrett's oesophagus: substantial interobserver variation
      between general and gastrointestinal pathologists.
AB  - AIMS: To determine interobserver variation in grading of dysplasia in Barrett's
      oesophagus (BO) between non-expert general pathologists and expert
      gastrointestinal pathologists on the one hand and between expert pathologists on
      the other hand. METHODS AND RESULTS: In this prospective multicentre study, non
      expert and expert pathologists graded biopsy specimens of 920 patients with
      endoscopic BO, which were blindly reviewed by one member of a panel of expert
      pathologists (panel experts) and by a second panel expert in case of disagreement
      on dysplasia grade. Agreement between two of three pathologists was established
      as the final diagnosis. Analysis was performed by kappa statistics. Due to
      absence of intestinal metaplasia, 127/920 (14%) patients were excluded. The
      interobserver agreement for dysplasia [no dysplasia (ND) versus indefinite for
      dysplasia/low-grade dysplasia (IND/LGD) versus high-grade dysplasia
      (HGD)/adenocarcinoma (AC)] between non-experts and first panel experts and
      between initial experts and first panel experts was fair (kappa = 0.24 and kappa
      = 0.27, respectively), and substantial for differentiation of HGD/AC from
      ND/IND/LGD (kappa = 0.62 and kappa = 0.58, respectively). CONCLUSIONS: There was
      considerable interobserver variability in the interpretation of ND or IND/LGD in
      BO between non-experts and experts, but also between expert pathologists. This
      suggests that less subjective markers are needed to determine the risk of
      developing AC in BO.

PMID- 17543083
TI  - Expression of Bax, Bcl-xL and Bcl-2 proteins in relation to grade of inflammation
      and stage of fibrosis in chronic hepatitis C.
AB  - AIMS: To determine the expression of regulators of apoptosis in chronic hepatitis
      C. METHODS AND RESULTS: Expression of Bax, Bcl-xL and Bcl-2 proteins was assessed
      immunohistochemically in liver biopsy specimens obtained from 89 adults with
      chronic hepatitis C. Expression of Bax in hepatocytes correlated inversely with
      grade of inflammation (P < 0.001) and stage of fibrosis (P = 0.011), classified
      according to the Scheuer score; expression of Bcl-xL in hepatocytes did not
      correlate with grade of inflammation (P = 0.106) or stage of fibrosis (P =
      0.078); maximum Bcl-xL expression was observed in grade 3 inflammation and stage
      4 fibrosis. Expression of Bcl-2 protein in hepatocytes was present in only two
      cases (both with advanced disease); the expression of Bcl-2 protein in
      interlobular bile duct epithelial cells correlated with the grade of inflammation
      (P = 0.018), but not with stage of fibrosis (P = 0.154). The expression of Bcl-2
      protein in lymphoid cells infiltrating portal zones and lobules did not correlate
      with grade of inflammation (P = 0.113) or stage of fibrosis (P = 0.815).
      CONCLUSION: Major differences in expression of studied proteins were observed in
      relation to grade of inflammation and stage of fibrosis in chronic hepatitis C.

PMID- 17543084
TI  - Expression of the UV-induced molecule, Gadd45, in atypical fibroxanthoma.

PMID- 17543085
TI  - Identification of neoplastic cells in the lymphocytic infiltrate associated with
      thin melanomas.

PMID- 17543086
TI  - Granular changes (Paneth cell-like) in epididymal epithelial cells are lysosomal
      in nature and are not markers of obstruction.

PMID- 17543087
TI  - Revision of the cytological diagnosis of CNS relapse into aseptic meningitis in a
      patient with TEL-AML1+ acute lymphoblastic leukaemia by FISH analysis of
      mononuclear cells in cerebrospinal fluid.

PMID- 17543088
TI  - Immunohistochemical detection of class III beta-tubulin in primary brain tumours:
      variable expression in most tumour types limits utility as a differential
      diagnostic marker.

PMID- 17543089
TI  - Multiple myeloma with loss of CD138 expression in two rare metastatic
      localizations, peritoneum and skin.

PMID- 17543090
TI  - Concomitant and fatal HHV-8+ multicentric Castleman's disease and Kaposi's
      sarcoma in the same lymph node of an HIV- liver transplant patient.

PMID- 17543091
TI  - Salivary duct carcinomas comprise phenotypically and genotypically diverse high
      grade neoplasms.

PMID- 17543092
TI  - Non-neoplastic nuclear atypia in endometrial epithelium in postmenopausal women
      on hormonal therapy.

PMID- 17543094
TI  - Characteristics of primary and immortalized fibroblast cells derived from the
      miniature and domestic pigs.
AB  - BACKGROUND: The pig, Sus scrofa domestica includes both the miniature and
      commercial domestic breed. These animals have influenced the human life and
      economies and have been studied throughout history. Although the miniature breeds
      are more recent and have increasingly been used in a variety of biomedical
      studies, their cell lines have rarely been established. Therefore, we sought to
      establish primary and immortal cell lines derived from both the miniature and
      domestic pig to better enable insight into possible in vivo growth differences.
      RESULTS: The in vitro lifespan of primary domestic pig fibroblast (PF) and
      miniature pig fibroblast (MPF) cells using a standard 3T3 protocol was
      determined. Both of the primary PF and MPF cells were shown to have a two-step
      replicative senescence barrier. Primary MPF cells exhibited a relatively shorter
      lifespan and slower proliferation rate compared to those of primary PF cells.
      Beyond senescence barriers, lifespan-extended PF and MPF cells were eventually
      established and indicated spontaneous cellular immortalization. In contrast to
      the immortalized PF cells, immortal MPF cells showed a transformed phenotype and
      possessed more frequent chromosomal abnormalities and loss of p53 regulatory
      function. The lifespan of primary MPF and PF cells was extended by inactivation
      of the p53 function using transduction by SV40LT without any detectable senescent
      phenotype. CONCLUSION: These results suggest that p53 signaling might be a major
      determinant for the replicative senescence in the MPF cells that have the shorter
      lifespan and slower growth rate compared to PF cells in vitro.

PMID- 17543095
TI  - In vitro angiogenesis and expression of nuclear factor kappaB and VEGF in high
      and low metastasis cell lines of salivary gland Adenoid Cystic Carcinoma.
AB  - BACKGROUND: Adenoid cystic carcinoma is a high malignant carcinoma characterized
      by intensive local invasion and high incidence of distant metastasis. Although
      many reports have demonstrated that angiogenesis has played an important role in
      tumor metastasis, the relationship between metastasis characters and angiogenesis
      ability in high and low metastasis cell lines of Adenoid cystic carcinoma has
      rarely been reported. The present study aimed to compare the angiogenesis ability
      of ACC-M (high metastasis) and ACC-2 (low metastasis) cell lines in vitro.
      Furthermore, the activity of nuclear factor kappaappa B and the expression of
      vascular endothelial growth factor (VEGF) in ACC-2 and ACC-M were also detected.
      METHODS: Electrophoretic mobility shift assay was used to detect nuclear factor
      kappaappa B activity. Semi-quantitative RT-PCR was used to quantify the mRNA
      level of VEGF. Immuofluorescence double staining and semi-quantitative confocal
      laser scanning analysis was carried out to detect nuclear factor kappaappa B
      nuclear localization and staining intensity of VEGF. The angiogenesis ability of
      ACC-M and ACC-2 was compared by an in vitro three-dimensional angiogenic model
      assay. The vector transfection assay was performed to transfect the PCMV
      IkappaBalphaM vector into ACCs cell lines expressing the phosphorylation
      defective IkappaBalphaM. RESULTS: Nuclear factor kappaappa B activity and the
      rate of nuclear factor kappaappa B nuclear localization in ACC-M was
      significantly higher than that in ACC-2. Moreover, ACC-M exhibited higher mRNA
      and protein levels of vascular endothelial growth factor than ACC-2. VEGF mRNA
      expression was effectively decreased by inhibition of nuclear factor kappaappa B
      activity. Furthermore, ACC-M could remarkably stimulate the migration and tube
      formation of endothelial cells and induce The umbilical vein endothelial cells
      sprouting into the gel matrix. CONCLUSION: These results implicated that ACCs
      cells with higher metastasis feature might present greater angiogenesis ability.

PMID- 17543096
TI  - Allelic and genotypic associations of DRD2 TaqI A polymorphism with heroin
      dependence in Spanish subjects: a case control study.
AB  - BACKGROUND: Conflicting associations with heroin dependence have been found
      involving the A1 allele of dopamine D2 receptor gene (DRD2) TaqI A polymorphism.
      METHODS: We compared two samples of unrelated Spanish individuals, all of
      European origin: 281 methadone-maintained heroin-dependent patients (207 males
      and 74 females) who frequently used non-opioid substances, and 145 control
      subjects (98 males and 47 females). RESULTS: The A1-A1 genotype was detected in
      7.1% of patients and 1.4% of controls (P = 0.011, odds ratio = 5.48, 95% CI 1.26
      23.78). Although the A1 allele was not associated with heroin dependence in the
      entire sample, the frequency of A1 allele was higher in male patients than in
      male controls (24.4% vs. 16.3%, P = 0.024, odds ratio = 1.65, 95% CI 1.07-2.57).
      A logistic regression analysis showed an interaction between DRD2 alleles and
      gender (odds ratio = 1.77, 95% CI 1.15-2.70). CONCLUSION: Our results indicate
      that, in Spanish individuals, genotypes of the DRD2 TaqI A polymorphism
      contribute to variations in the risk of heroin dependence, while single alleles
      contribute only in males.

PMID- 17543097
TI  - Including metabolite concentrations into flux balance analysis: thermodynamic
      realizability as a constraint on flux distributions in metabolic networks.
AB  - BACKGROUND: In recent years, constrained optimization - usually referred to as
      flux balance analysis (FBA) - has become a widely applied method for the
      computation of stationary fluxes in large-scale metabolic networks. The striking
      advantage of FBA as compared to kinetic modeling is that it basically requires
      only knowledge of the stoichiometry of the network. On the other hand, results of
      FBA are to a large degree hypothetical because the method relies on plausible but
      hardly provable optimality principles that are thought to govern metabolic flux
      distributions. RESULTS: To augment the reliability of FBA-based flux calculations
      we propose an additional side constraint which assures thermodynamic
      realizability, i.e. that the flux directions are consistent with the
      corresponding changes of Gibb's free energies. The latter depend on metabolite
      levels for which plausible ranges can be inferred from experimental data.
      Computationally, our method results in the solution of a mixed integer linear
      optimization problem with quadratic scoring function. An optimal flux
      distribution together with a metabolite profile is determined which assures
      thermodynamic realizability with minimal deviations of metabolite levels from
      their expected values. We applied our novel approach to two exemplary metabolic
      networks of different complexity, the metabolic core network of erythrocytes (30
      reactions) and the metabolic network iJR904 of Escherichia coli (931 reactions).
      Our calculations show that increasing network complexity entails increasing
      sensitivity of predicted flux distributions to variations of standard Gibb's free
      energy changes and metabolite concentration ranges. We demonstrate the usefulness
      of our method for assessing critical concentrations of external metabolites
      preventing attainment of a metabolic steady state. CONCLUSION: Our method
      incorporates the thermodynamic link between flux directions and metabolite
      concentrations into a practical computational algorithm. The weakness of
      conventional FBA to rely on intuitive assumptions about the reversibility of
      biochemical reactions is overcome. This enables the computation of reliable flux
      distributions even under extreme conditions of the network (e.g. enzyme
      inhibition, depletion of substrates or accumulation of end products) where
      metabolite concentrations may be drastically altered.

PMID- 17543098
TI  - Assessing household wealth in health studies in developing countries: a
      comparison of participatory wealth ranking and survey techniques from rural South
      Africa.
AB  - BACKGROUND: Accurate tools for assessing household wealth are essential for many
      health studies in developing countries. Household survey and participatory wealth
      ranking (PWR) are two approaches to generate data for this purpose. METHODS: A
      household survey and PWR were conducted among eight villages in rural South
      Africa. We developed three indicators of household wealth using the data. One
      indicator used PWR data only, one used principal components analysis to combine
      data from the survey, while the final indicator used survey data combined in a
      manner informed by the PWR. We assessed internal consistency of the indices and
      assessed their level of agreement in ranking household wealth. RESULTS: Food
      security, asset ownership, housing quality and employment were important
      indicators of household wealth. PWR, consisting of three independent rankings of
      9671 households, showed a high level of internal consistency (intraclass
      correlation coefficient 0.81, 95% CI 0.79-0.82). Data on 1429 households were
      available from all three techniques. There was moderate agreement in ranking
      households into wealth tertiles between the two indicators based on survey data
      (spearman rho = 0.69, kappa = 0.43), but only limited agreement between these
      techniques and the PWR data (spearman rho = 0.38 and 0.31, kappa = 0.20 and
      0.17). CONCLUSION: Both PWR and household survey can provide a rapid assessment
      of household wealth. Each technique had strengths and weaknesses. Reasons for
      differences might include data inaccuracies or limitations in the methods by
      which information was weighted. Alternatively, the techniques may measure
      different things. More research is needed to increase the validity of measures of
      socioeconomic position used in health studies in developing countries.

PMID- 17543099
TI  - The use of personal digital assistants for data entry at the point of collection
      in a large household survey in southern Tanzania.
AB  - BACKGROUND: Survey data are traditionally collected using pen-and-paper, with
      double data entry, comparison of entries and reconciliation of discrepancies
      before data cleaning can commence. We used Personal Digital Assistants (PDAs) for
      data entry at the point of collection, to save time and enhance the quality of
      data in a survey of over 21,000 scattered rural households in southern Tanzania.
      METHODS: Pendragon Forms 4.0 software was used to develop a modular questionnaire
      designed to record information on household residents, birth histories, child
      health and health-seeking behaviour. The questionnaire was loaded onto Palm m130
      PDAs with 8 Mb RAM. One hundred and twenty interviewers, the vast majority with
      no more than four years of secondary education and very few with any prior
      computer experience, were trained to interview using the PDAs. The 13 survey
      teams, each with a supervisor, laptop and a four-wheel drive vehicle, were
      supported by two back-up vehicles during the two months of field activities. PDAs
      and laptop computers were charged using solar and in-car chargers. Logical checks
      were performed and skip patterns taken care of at the time of data entry. Data
      records could not be edited after leaving each household, to ensure the integrity
      of the data from each interview. Data were downloaded to the laptop computers and
      daily summary reports produced to evaluate the completeness of data collection.
      Data were backed up at three levels: (i) at the end of every module, data were
      backed up onto storage cards in the PDA; (ii) at the end of every day, data were
      downloaded to laptop computers; and (iii) a compact disc (CD) was made of each
      team's data each day.A small group of interviewees from the community, as well as
      supervisors and interviewers, were asked about their attitudes to the use of
      PDAs. RESULTS: Following two weeks of training and piloting, data were collected
      from 21,600 households (83,346 individuals) over a seven-week period in July
      August 2004. No PDA-related problems or data loss were encountered. Fieldwork
      ended on 26 August 2004, the full dataset was available on a CD within 24 hours
      and the results of initial analyses were presented to district authorities on 28
      August. Data completeness was over 99%. The PDAs were well accepted by both
      interviewees and interviewers. CONCLUSION: The use of PDAs eliminated the usual
      time-consuming and error-prone process of data entry and validation. PDAs are a
      promising tool for field research in Africa.

PMID- 17543100
TI  - Sampling in health geography: reconciling geographical objectives and
      probabilistic methods. An example of a health survey in Vientiane (Lao PDR).
AB  - BACKGROUND: Geographical objectives and probabilistic methods are difficult to
      reconcile in a unique health survey. Probabilistic methods focus on individuals
      to provide estimates of a variable's prevalence with a certain precision, while
      geographical approaches emphasise the selection of specific areas to study
      interactions between spatial characteristics and health outcomes. A sample
      selected from a small number of specific areas creates statistical challenges:
      the observations are not independent at the local level, and this results in poor
      statistical validity at the global level. Therefore, it is difficult to construct
      a sample that is appropriate for both geographical and probability methods.
      METHODS: We used a two-stage selection procedure with a first non-random stage of
      selection of clusters. Instead of randomly selecting clusters, we deliberately
      chose a group of clusters, which as a whole would contain all the variation in
      health measures in the population. As there was no health information available
      before the survey, we selected a priori determinants that can influence the
      spatial homogeneity of the health characteristics. This method yields a
      distribution of variables in the sample that closely resembles that in the
      overall population, something that cannot be guaranteed with randomly-selected
      clusters, especially if the number of selected clusters is small. In this way, we
      were able to survey specific areas while minimising design effects and maximising
      statistical precision. APPLICATION: We applied this strategy in a health survey
      carried out in Vientiane, Lao People's Democratic Republic. We selected well
      known health determinants with unequal spatial distribution within the city:
      nationality and literacy. We deliberately selected a combination of clusters
      whose distribution of nationality and literacy is similar to the distribution in
      the general population. CONCLUSION: This paper describes the conceptual reasoning
      behind the construction of the survey sample and shows that it can be
      advantageous to choose clusters using reasoned hypotheses, based on both
      probability and geographical approaches, in contrast to a conventional, random
      cluster selection strategy.

PMID- 17543101
TI  - Optimisation of the T-square sampling method to estimate population sizes.
AB  - Population size and density estimates are needed to plan resource requirements
      and plan health related interventions. Sampling frames are not always available
      necessitating surveys using non-standard household sampling methods. These
      surveys are time-consuming, difficult to validate, and their implementation could
      be optimised. Here, we discuss an example of an optimisation procedure for rapid
      population estimation using T-Square sampling which has been used recently to
      estimate population sizes in emergencies. A two-stage process was proposed to
      optimise the T-Square method wherein the first stage optimises the sample size
      and the second stage optimises the pathway connecting the sampling points. The
      proposed procedure yields an optimal solution if the distribution of households
      is described by a spatially homogeneous Poisson process and can be sub-optimal
      otherwise. This research provides the first step in exploring how optimisation
      techniques could be applied to survey designs thereby providing more timely and
      accurate information for planning interventions.

PMID- 17543102
TI  - Don't spin the pen: two alternative methods for second-stage sampling in urban
      cluster surveys.
AB  - In two-stage cluster surveys, the traditional method used in second-stage
      sampling (in which the first household in a cluster is selected) is time
      consuming and may result in biased estimates of the indicator of interest.
      Firstly, a random direction from the center of the cluster is selected, usually
      by spinning a pen. The houses along that direction are then counted out to the
      boundary of the cluster, and one is then selected at random to be the first
      household surveyed. This process favors households towards the center of the
      cluster, but it could easily be improved. During a recent meningitis vaccination
      coverage survey in Maradi, Niger, we compared this method of first household
      selection to two alternatives in urban zones: 1) using a superimposed grid on the
      map of the cluster area and randomly selecting an intersection; and 2) drawing
      the perimeter of the cluster area using a Global Positioning System (GPS) and
      randomly selecting one point within the perimeter. Although we only compared a
      limited number of clusters using each method, we found the sampling grid method
      to be the fastest and easiest for field survey teams, although it does require a
      map of the area. Selecting a random GPS point was also found to be a good method,
      once adequate training can be provided. Spinning the pen and counting households
      to the boundary was the most complicated and time-consuming. The two methods
      tested here represent simpler, quicker and potentially more robust alternatives
      to spinning the pen for cluster surveys in urban areas. However, in rural areas,
      these alternatives would favor initial household selection from lower density (or
      even potentially empty) areas. Bearing in mind these limitations, as well as
      available resources and feasibility, investigators should choose the most
      appropriate method for their particular survey context.

PMID- 17543103
TI  - Wanted: studies on mortality estimation methods for humanitarian emergencies,
      suggestions for future research.
AB  - Measuring rates and circumstances of population mortality (in particular crude
      and under-5 year mortality rates) is essential to evidence-based humanitarian
      relief interventions. Because prospective vital event registration is absent or
      deteriorates in nearly all crisis-affected populations, retrospective household
      surveys are often used to estimate and describe patterns of mortality. Originally
      designed for measuring vaccination coverage, the two-stage cluster survey
      methodology is frequently employed to measure mortality retrospectively due to
      limited time and resources during humanitarian emergencies. The method tends to
      be followed without considering alternatives, and there is a need for expert
      advice to guide health workers measuring mortality in the field. In a workshop in
      France in June 2006, we deliberated the problems inherent in this method when
      applied to measure outcomes other than vaccine coverage and acute malnutrition
      (specifically, mortality), and considered recommendations for improvement. Here
      we describe these recommendations and outline outstanding issues in three main
      problem areas in emergency mortality assessment discussed during the workshop:
      sampling, household data collection issues, and cause of death ascertainment. We
      urge greater research on these issues. As humanitarian emergencies become ever
      more complex, all agencies should benefit from the most recently tried and tested
      survey tools.

PMID- 17543104
TI  - A review of methodology and analysis of nutrition and mortality surveys conducted
      in humanitarian emergencies from October 1993 to April 2004.
AB  - BACKGROUND: Malnutrition prevalence and mortality rates are increasingly used as
      essential indicators to assess the severity of a crisis, to follow trends, and to
      guide decision-making, including allocation of funds. Although consensus has
      slowly developed on the methodology to accurately measure these indicators,
      errors in the application of the survey methodology and analysis have persisted.
      The aim of this study was to identify common methodological weaknesses in
      nutrition and mortality surveys and to provide practical recommendations for
      improvement. METHODS: Nutrition (N = 368) and crude mortality rate (CMR; N = 158)
      surveys conducted by 33 non-governmental organisations and United Nations
      agencies in 17 countries from October 1993 to April 2004 were analysed for
      sampling validity, precision, quality of measurement and calculation according to
      several criteria. RESULTS: One hundred and thirty (35.3%) nutrition surveys and 5
      (3.2%) CMR surveys met the criteria for quality. Quality of surveys varied
      significantly depending on the agency. The proportion of nutrition surveys that
      met criteria for quality rose significantly from 1993 to 2004; there was no
      improvement for mortality surveys during this period. CONCLUSION: Significant
      errors and imprecision in the methodology and reporting of nutrition and
      mortality surveys were identified. While there was an improvement in the quality
      of nutrition surveys over the years, the quality of mortality surveys remained
      poor. Recent initiatives aimed at standardising nutrition and mortality survey
      quality should be strengthened. There are still a number of methodological issues
      in nutrition and mortality surveys in humanitarian emergencies that need further
      study.

PMID- 17543105
TI  - Mortality and nutrition surveys by non-governmental organisations. Perspectives
      from the CE-DAT database.
AB  - In this paper we explore the strengths and gaps among NGO surveys based on an
      analysis of the records held in the CE-DAT database at CRED. We conclude by
      recommending the priority areas for strengthening NGO capacity to undertake
      surveys and ways to improve data quality in general.

PMID- 17543106
TI  - General Practice as a career choice among undergraduate medical students in
      Greece.
AB  - BACKGROUND: Although General Practice (GP) was recognized as a medical specialty
      in Greece in 1986, the number of GPs is insufficient to cover needs and only few
      medical graduates choose GP as a career option. In the present study we
      investigated the profile of medical students in terms of their decisions
      regarding specialization and the possible association of career choices different
      from GP with the status of undergraduate training regarding GP. METHODS: The
      sample consisted of final year students in the Medical School of the University
      of Athens, Greece. Students filled in a self-reported questionnaire focusing on
      medical specialization, and GP in particular. RESULTS: Response rate was 82.5%
      with 1021 questionnaires collected, out of 1237 eligible medical students. Only
      44 out of the 1021 (4.3%) respondents stated that GP is -or could be- among their
      choices for specialty. The most popular medical specialty was General Surgery
      (10.9%), followed by Cardiology (9.6%), Endocrinology (8.7%) and Obstetrics
      Gynaecology (8.3%). The most common criterion for choosing GP was the guaranteed
      employment on completion of the residency (54.6%) while a 56.6% of total
      respondents were positive to the introduction of GP/FM as a curriculum course
      during University studies. CONCLUSION: Despite the great needs, GP specialty is
      currently not a career option among undergraduate students of the greater Medical
      University in Greece and is still held in low esteem. A university department
      responsible for undergraduate teaching, promotion and research in GP (where not
      available) is essential; the status of undergraduate training in general
      practice/family medicine seems to be one of the most important factors that
      influence physician career choices regarding primary care specialties.

PMID- 17543107
TI  - Who should be undertaking population-based surveys in humanitarian emergencies?
AB  - BACKGROUND: Timely and accurate data are necessary to prioritise and effectively
      respond to humanitarian emergencies. 30-by-30 cluster surveys are commonly used
      in humanitarian emergencies because of their purported simplicity and reasonable
      validity and precision. Agencies have increasingly used 30-by-30 cluster surveys
      to undertake measurements beyond immunisation coverage and nutritional status.
      Methodological errors in cluster surveys have likely occurred for decades in
      humanitarian emergencies, often with unknown or unevaluated consequences.
      DISCUSSION: Most surveys in humanitarian emergencies are done by non-governmental
      organisations (NGOs). Some undertake good quality surveys while others have an
      already overburdened staff with limited epidemiological skills. Manuals
      explaining cluster survey methodology are available and in use. However, it is
      debatable as to whether using standardised, 'cookbook' survey methodologies are
      appropriate. Coordination of surveys is often lacking. If a coordinating body is
      established, as recommended, it is questionable whether it should have sole
      authority to release surveys due to insufficient independence. Donors should
      provide sufficient funding for personnel, training, and survey implementation,
      and not solely for direct programme implementation. SUMMARY: A dedicated corps of
      trained epidemiologists needs to be identified and made available to undertake
      surveys in humanitarian emergencies. NGOs in the field may need to form an
      alliance with certain specialised agencies or pool technically capable personnel.
      If NGOs continue to do surveys by themselves, a simple training manual with
      sample survey questionnaires, methodology, standardised files for data entry and
      analysis, and manual for interpretation should be developed and modified locally
      for each situation. At the beginning of an emergency, a central coordinating body
      should be established that has sufficient authority to set survey standards,
      coordinate when and where surveys should be undertaken and act as a survey
      repository. Technical expertise is expensive and donors must pay for it. As
      donors increasingly demand evidence-based programming, they have an obligation to
      ensure that sufficient funds are provided so organisations have adequate
      technical staff.

PMID- 17543108
TI  - Perception of acoustically complex phonological features in vowels is reflected
      in the induced brain-magnetic activity.
AB  - A central issue in speech recognition is which basic units of speech are
      extracted by the auditory system and used for lexical access. One suggestion is
      that complex acoustic-phonetic information is mapped onto abstract phonological
      representations of speech and that a finite set of phonological features is used
      to guide speech perception. Previous studies analyzing the N1m component of the
      auditory evoked field have shown that this holds for the acoustically simple
      feature place of articulation. Brain magnetic correlates indexing the extraction
      of acoustically more complex features, such as lip rounding (ROUND) in vowels,
      have not been unraveled yet. The present study uses magnetoencephalography (MEG)
      to describe the spatial-temporal neural dynamics underlying the extraction of
      phonological features. We examined the induced electromagnetic brain response to
      German vowels and found the event-related desynchronization in the upper beta
      band to be prolonged for those vowels that exhibit the lip rounding feature
      (ROUND). It was the presence of that feature rather than circumscribed single
      acoustic parameters, such as their formant frequencies, which explained the
      differences between the experimental conditions. We conclude that the prolonged
      event-related desynchronization in the upper beta-band correlates with the
      computational effort for the extraction of acoustically complex phonological
      features from the speech signal. The results provide an additional biomagnetic
      parameter to study mechanisms of speech perception.

PMID- 17543109
TI  - Nasal carriage of a single clone of community-acquired methicillin-resistant
      Staphylococcus aureus among kindergarten attendees in northern Taiwan.
AB  - BACKGROUND: To evaluate the prevalence and microbiological characterization of
      community-acquired (CA) methicillin-resistant Staphylococcus aureus (MRSA) nasal
      carriage in a kindergarten. METHODS: Point prevalence study. Nasal swabs were
      collected from healthy children younger than 7 years of age who were attending a
      kindergarten in Taipei, Taiwan. A parent questionnaire regarding MRSA risk
      factors was administered simultaneously. All CA-MRSA colonization isolates were
      archived for subsequent antimicrobial susceptibility and molecular typing.
      RESULTS: Of the 68 children who participated in the study, 17 (25%) had S. aureus
      isolated from nasal swabs. Nine (13.2%) of the 68 children had CA-MRSA carriage,
      and none of them had any identified risk factors. Antimicrobial susceptibility
      testing revealed all of the 9 CA-MRSA colonization isolates had uniformly high
      resistance (100%) to both clindamycin and erythromycin, the macrolide-lincosamide
      streptogramin-constitutive phenotype and the ermB gene. Pulsed-field gel
      electrophoresis revealed 8 (88.9%) of 9 CA-MRSA colonization isolates were
      genetically related and multilocus sequence typing revealed all isolates had
      sequence type 59. All of the colonization isolates carried the staphylococcal
      cassette chromosome mec type IV, but none were positive for the Panton-Valentine
      leukocidin genes. CONCLUSION: The results of this study suggest that a single
      predominant CA-MRSA colonization strain featuring high clindamycin resistance
      circulated in this kindergarten. Additionally, due to the established
      transmissibility of colonization isolates, the high prevalence of nasal carriage
      of CA-MRSA among healthy attendees in kindergartens may indicate the accelerated
      spread of CA-MRSA in the community.

PMID- 17543110
TI  - Cloning and characterization of microRNAs from wheat (Triticum aestivum L.).
AB  - BACKGROUND: MicroRNAs (miRNAs) are a class of small, non-coding regulatory RNAs
      that regulate gene expression by guiding target mRNA cleavage or translational
      inhibition. So far, identification of miRNAs has been limited to a few model
      plant species, such as Arabidopsis, rice and Populus, whose genomes have been
      sequenced. Wheat is one of the most important cereal crops worldwide. To date,
      only a few conserved miRNAs have been predicted in wheat and the computational
      identification of wheat miRNAs requires the genome sequence, which is unknown.
      RESULTS: To identify novel as well as conserved miRNAs in wheat (Triticum
      aestivum L.), we constructed a small RNA library. High throughput sequencing of
      the library and subsequent analysis revealed the identification of 58 miRNAs,
      comprising 43 miRNA families. Of these, 35 miRNAs belong to 20 conserved miRNA
      families. The remaining 23 miRNAs are novel and form 23 miRNA families in wheat;
      more importantly, 4 of these new miRNAs (miR506, miR510, miR514 and miR516)
      appear to be monocot-specific. Northern blot analysis indicated that some of the
      new miRNAs are preferentially expressed in certain tissues. Based on sequence
      homology, we predicted 46 potential targets. Thus, we have identified a large
      number of monocot-specific and wheat-specific miRNAs. These results indicate that
      both conserved and wheat-specific miRNAs play important roles in wheat growth and
      development, stress responses and other physiological processes. CONCLUSION: This
      study led to the discovery of 58 wheat miRNAs comprising 43 miRNA families; 20 of
      these families are conserved and 23 are novel in wheat. It provides a first large
      scale cloning and characterization of wheat miRNAs and their predicted targets.

PMID- 17543111
TI  - Disclosing conflicts of interest in German publications concerning health
      services research.
AB  - BACKGROUND: The influence of the pharmaceutical industry and other stakeholders
      on medical science has been increasingly criticised. When dealing with conflicts
      of interest in scientific publications it is important to ensure the best
      possible transparency. The objective of this work is to examine the disclosure
      practice of financial and non-financial conflicts of interest in German language
      publications concerning health services research for the first time. METHODS: We
      performed a systematic literature search in the PubMed data base using the MeSH
      term "health services research". The review was conducted on July 10, 2006,
      setting the limits "dates: published in the last 2 years" and "languages: German"
      (only articles with abstracts). 124 articles in 31 magazines were found. In the
      magazines the instructions for authors were examined as to whether a statement on
      conflicts of interest is expected--and if, in which form. Regarding the articles
      in the journals which require a statement, we examined whether the statement is
      explicitly published. The results are descriptively represented. RESULTS: 13
      magazines (42%) do not require any statement on conflicts of interest, whereas 18
      journals (58%) expect a statement. Two of these 18 magazines refer explicitly to
      the uniform requirements of the International Committee of the Medical Journal
      Editors (ICMJE); the remaining 16 magazines give differently accentuated
      instructions on how to disclose conflicts of interest, whereby the focus is
      primarily on financial issues. A statement on conflicts of interest is explicitly
      published in 11 of the 71 articles (15%) which are found in the magazines that
      require a statement with the submission of a manuscript. Related to the total
      number of included articles, this means that the reader explicitly receives
      information on potential conflicts of interest in 9% of the cases (11 of 124
      articles). Statements of others that are involved in the publication process
      (reviewers, editors) are not available in any of the articles examined.
      CONCLUSION: A better sensitization for possible conflicts of interest in German
      publications concerning health services research is necessary. We suggest
      tightening the criteria for disclosure in the instructions for authors in the
      scientific journals. Among other things the equivalent consideration of financial
      and non-financial conflicts of interest as well as the obligatory publication of
      the statements should be part of good practice.

PMID- 17543112
TI  - Generic drug policy in Australia: a community pharmacy perspective.
AB  - This article provides a commentary, from a community pharmacy perspective, on the
      policy environment for the pharmacy sector in Australia, with a particular focus
      on present challenges arising from proposals to achieve substantial PBS cost
      savings from an anticipated surge of new generic drugs. Some $2 billion of
      medicines currently on the PBS will come off patent in the next 4 years. This
      growth comes from a low base where generics currently account for only 15% of the
      total PBS budget. Remuneration for PBS dispensing is fixed through five year
      agreements with the government, so trading terms on generics are important for
      the cross-subsidy of other dispensing activities and professional services. These
      trading terms (discounts provided by generics suppliers) have become part of the
      overall cost and revenue structure of pharmacies. Despite these arrangements,
      generic substitution rates in Australia are lower than in most comparable
      countries, which the government views as an opportunity to promote generic use.
      The future of generic drug supply via the PBS is important to allow consumers
      access to medications at the lowest possible price and to provide space for PBS
      listing of new and expensive drugs. But considerations of PBS reform need to take
      account of the role and viability of community pharmacy sector as provider of
      pharmaceuticals in a timely and efficient manner to Australian residents.

PMID- 17543113
TI  - 'Linkage' pharmaceutical evergreening in Canada and Australia.
AB  - 'Evergreening' is not a formal concept of patent law. It is best understood as a
      social idea used to refer to the myriad ways in which pharmaceutical patent
      owners utilise the law and related regulatory processes to extend their high rent
      earning intellectual monopoly privileges, particularly over highly profitable
      (either in total sales volume or price per unit) 'blockbuster' drugs. Thus, while
      the courts are an instrument frequently used by pharmaceutical brand name
      manufacturers to prolong their patent royalties, 'evergreening' is rarely
      mentioned explicitly by judges in patent protection cases. The term usually
      refers to threats made to competitors about a brand-name manufacturer's tactical
      use of pharmaceutical patents (including over uses, delivery systems and even
      packaging), not to extension of any particular patent over an active product
      ingredient. This article focuses in particular on the 'evergreening' potential of
      so-called 'linkage' provisions, imposed on the regulatory (safety, quality and
      efficacy) approval systems for generic pharmaceuticals of Canada and Australia,
      by specific articles in trade agreements with the US. These 'linkage' provisions
      have also recently appeared in the Korea-US Free Trade Agreement (KORUSFTA). They
      require such drug regulators to facilitate notification of, or even prevent, any
      potential patent infringement by a generic pharmaceutical manufacturer. This
      article explores the regulatory lessons to be learnt from Canada's and
      Australia's shared experience in terms of minimizing potential adverse impacts of
      such 'linkage evergreening' provisions on drug costs and thereby potentially on
      citizen's access to affordable, essential medicines.

PMID- 17543114
TI  - Challenges for Australia's Bio/Nanopharma Policies: trade deals, public goods and
      reference pricing in sustainable industrial renewal.
AB  - Industrial renewal in the bio/nanopharma sector is important for the long term
      strength of the Australian economy and for the health of its citizens. A variety
      of factors, however, may have caused inadequate attention to focus on
      systematically promoting domestic generic and small biotechnology manufacturers
      in Australian health policy. Despite recent clarifications of 'springboarding'
      capacity in intellectual property legislation, federal government requirements
      for specific generic price reductions on market entry and the potential erosion
      of reference pricing through new F1 and F2 categories for the purposes of
      Pharmaceutical Benefits Scheme (PBS) assessments, do not appear to be coherently
      designed to sustainably position this industry sector in 'biologics,'
      nanotherapeutics and pharmacogenetics. There also appears to have been little
      attention paid in this context to policies fostering industry sustainability and
      public affordability (as encouraged by the National Medicines Policy). One
      notable example includes that failure to consider facilitating mutual exchanges
      on regulatory assessment of health technology safety and cost-effectiveness
      (including reference pricing) in the context of ongoing free trade negotiations
      between Australia and China (the latter soon to possess the world's largest
      generic pharmaceutical manufacturing capacity). The importance of a thriving
      Australian domestic generic pharmaceutical and bio/nano tech industry in terms of
      biosecurity, similarly appears to have been given insufficient policy
      attention.Reasons for such policy oversights may relate to increasing
      interrelationships between generic and 'brand-name' manufacturers and the scale
      of investment required for the Australian generics and bio/nano technology sector
      to be a significant driver of local production. It might also result from
      singularly effective lobbying pressure exerted by Medicines Australia, the 'brand
      name' pharmaceutical industry association, utilising controversial
      interpretations of reward of pharmaceutical 'innovation' provisions in the
      Australia-US Free Trade Agreement (AUSFTA) through the policy-development
      mechanisms of the AUSFTA Medicines Working Group and most recently an Innovative
      Medicines Working Group with the Department of Health and Ageing. This paper
      critically analyses such arguments in the context of emerging challenges for
      sustainable industrial renewal in Australia's bio/nanopharma sector.

PMID- 17543115
TI  - The global biopharma industry and the rise of Indian drug multinationals:
      implications for Australian generics policy.
AB  - This article provides a synopsis of the new dynamics of the global biopharma
      industry. The emergence of global generics companies with capabilities
      approximating those of 'big pharma' has accelerated the blurring of boundaries
      between the innovator and generics sectors. Biotechnology-based products form a
      large and growing segment of prescription drug markets and regulatory pathways
      for biogenerics are imminent. Indian biopharma multinationals with large-scale
      efficient manufacturing plants and growing R&D capabilities are now major
      suppliers of Active Pharmaceutical Ingredients (APIs) and generic drugs across
      both developed and developing countries. In response to generic competition,
      innovator companies employ a range of life cycle management techniques, including
      the launch of 'authorised generics'. The generics segment in Australia will see
      high growth rates in coming years but the prospect for local manufacturing is
      bleak. The availability of cheap generics in international markets has put
      pressure on Pharmaceutical Benefits Scheme (PBS) pricing arrangements, and a new
      policy direction was announced in November 2006. Lower generics prices will have
      a negative impact on some incumbent suppliers but industrial renewal policies for
      the medicines industry in Australia are better focused on higher value R&D
      activities and niche manufacturing of sophisticated products.

PMID- 17543116
TI  - Reshaping Australian drug policy: the dilemmas of generic medicines policy.

PMID- 17543117
TI  - Distinguishing importation from diversification of quinolone-resistant Neisseria
      gonorrhoeae by molecular evolutionary analysis.
AB  - BACKGROUND: Distinguishing the recent introduction of quinolone resistant
      gonococci into a population from diversification of resistant strains already in
      the population is important for planning effective infection control strategies.
      We applied molecular evolutionary analyses to DNA sequences from 9 housekeeping
      genes and gyrA, parC and porB of 24 quinolone resistant N. gonorrhoeae (QRNG) and
      24 quinolone sensitive isolates collected in Israel during 2000-2001. RESULTS:
      Phylogenetic and eBURST analyses and estimates of divergence time indicated QRNG
      were introduced on 3 separate occasions and underwent limited diversification by
      mutation, deletion and horizontal gene transfer. Reconstruction of N. gonorrhoeae
      demography showed a slowly declining effective strain population size from 1976
      to 1993, rapid decline between 1994 and 1999, and an increase from 1999 to 2001.
      This is partially attributable to declining gonorrhea case rates from 1973 to
      1994. Additional contributing factors are selective sweeps of antibiotic
      resistant gonococci and increased transmission from sex workers. The abrupt
      decline in the mid-1990s heralded an increased incidence of gonorrhea from 1997
      to the present. The subsequent increase in effective strain population size since
      1999 reflects the increased gonococcal census population and introduction of
      quinolone resistance strains. CONCLUSION: Our study demonstrates the effective
      use of population genetic approaches to assess recent and historical population
      dynamics of N. gonorrhoeae.

PMID- 17543118
TI  - Optimal coordination of maximal-effort horizontal and vertical jump motions--a
      computer simulation study.
AB  - BACKGROUND: The purpose of this study was to investigate the coordination
      strategy of maximal-effort horizontal jumping in comparison with vertical
      jumping, using the methodology of computer simulation. METHODS: A skeletal model
      that has nine rigid body segments and twenty degrees of freedom was developed.
      Thirty-two Hill-type lower limb muscles were attached to the model. The
      excitation-contraction dynamics of the contractile element, the tissues around
      the joints to limit the joint range of motion, as well as the foot-ground
      interaction were implemented. Simulations were initiated from an identical
      standing posture for both motions. Optimal pattern of the activation input signal
      was searched through numerical optimization. For the horizontal jumping, the goal
      was to maximize the horizontal distance traveled by the body's center of mass.
      For the vertical jumping, the goal was to maximize the height reached by the
      body's center of mass. RESULTS: As a result, it was found that the hip joint was
      utilized more vigorously in the horizontal jumping than in the vertical jumping.
      The muscles that have a function of joint flexion such as the m. iliopsoas, m.
      rectus femoris and m. tibialis anterior were activated to a greater level during
      the countermovement in the horizontal jumping with an effect of moving the body's
      center of mass in the forward direction. Muscular work was transferred to the
      mechanical energy of the body's center of mass more effectively in the horizontal
      jump, which resulted in a greater energy gain of the body's center of mass
      throughout the motion. CONCLUSION: These differences in the optimal coordination
      strategy seem to be caused from the requirement that the body's center of mass
      needs to be located above the feet in a vertical jumping, whereas this
      requirement is not so strict in a horizontal jumping.

PMID- 17543119
TI  - Saccharomyces cerevisiae FKBP12 binds Arabidopsis thaliana TOR and its expression
      in plants leads to rapamycin susceptibility.
AB  - BACKGROUND: The eukaryotic TOR pathway controls translation, growth and the cell
      cycle in response to environmental signals such as nutrients or growth
      stimulating factors. The TOR protein kinase can be inactivated by the antibiotic
      rapamycin following the formation of a ternary complex between TOR, rapamycin and
      FKBP12 proteins. The TOR protein is also found in higher plants despite the fact
      that they are rapamycin insensitive. Previous findings using the yeast two hybrid
      system suggest that the FKBP12 plant homolog is unable to form a complex with
      rapamycin and TOR, while the FRB domain of plant TOR is still able to bind to
      heterologous FKBP12 in the presence of rapamycin. The resistance to rapamycin is
      therefore limiting the molecular dissection of the TOR pathway in higher plants.
      RESULTS: Here we show that none of the FKBPs from the model plant Arabidopsis
      (AtFKBPs) is able to form a ternary complex with the FRB domain of AtTOR in the
      presence of rapamycin in a two hybrid system. An antibody has been raised against
      the AtTOR protein and binding of recombinant yeast ScFKBP12 to native Arabidopsis
      TOR in the presence of rapamycin was demonstrated in pull-down experiments.
      Transgenic lines expressing ScFKBP12 were produced and were found to display a
      rapamycin-dependent reduction of the primary root growth and a lowered
      accumulation of high molecular weight polysomes. CONCLUSION: These results
      further strengthen the idea that plant resistance to rapamycin evolved as a
      consequence of mutations in plant FKBP proteins. The production of rapamycin
      sensitive plants through the expression of the ScFKBP12 protein illustrates the
      conservation of the TOR pathway in eukaryotes. Since AtTOR null mutants were
      found to be embryo lethal 1, transgenic ScFKBP12 plants will provide an useful
      tool for the post-embryonic study of plant TOR functions. This work also
      establish for the first time a link between TOR activity and translation in plant
      cells.

PMID- 17543120
TI  - Recombinant nucleases CEL I from celery and SP I from spinach for mutation
      detection.
AB  - BACKGROUND: The detection of unknown mutations is important in research and
      medicine. For this purpose, a mismatch-specific endonuclease CEL I from celery
      has been established as a useful tool in high throughput projects. Previously,
      CEL I-like activities were described only in a variety of plants and could not be
      expressed in an active form in bacteria. RESULTS: We describe expression of
      active recombinant plant mismatch endonucleases and modification of their
      activities. We also report the cloning of a CEL I ortholog from Spinacia oleracea
      (spinach) which we termed SP I nuclease. Active CEL I and SP I nucleases were
      expressed as C-terminal hexahistidine fusions and affinity purified from the cell
      culture media. Both recombinant enzymes were active in mutation detection in
      BRCA1 gene of patient-derived DNA. Native SP nuclease purified from spinach is
      unable to incise at single-nucleotide substitutions and loops containing a
      guanine nucleotide, but the recombinant SP I nuclease can cut at these sites.
      CONCLUSION: The insect cell-expressed CEL I orthologs may not be identical to
      their native counterparts purified from plant tissues. The present expression
      system should facilitate further development of CEL I-based mutation detection
      technologies.

PMID- 17543121
TI  - Comprehensive serial analysis of gene expression of the cervical transcriptome.
AB  - BACKGROUND: More than half of the approximately 500,000 women diagnosed with
      cervical cancer worldwide each year will die from this disease. Investigation of
      genes expressed in precancer lesions compared to those expressed in normal
      cervical epithelium will yield insight into the early stages of disease. As such,
      establishing a baseline from which to compare to, is critical in elucidating the
      abnormal biology of disease. In this study we examine the normal cervical tissue
      transcriptome and investigate the similarities and differences in relation to CIN
      III by Long-SAGE (L-SAGE). RESULTS: We have sequenced 691,390 tags from four L
      SAGE libraries increasing the existing gene expression data on cervical tissue by
      20 fold. One-hundred and eighteen unique tags were highly expressed in normal
      cervical tissue and 107 of them mapped to unique genes, most belong to the
      ribosomal, calcium-binding and keratinizing gene families. We assessed these
      genes for aberrant expression in CIN III and five genes showed altered
      expression. In addition, we have identified twelve unique HPV 16 SAGE tags in the
      CIN III libraries absent in the normal libraries. CONCLUSION: Establishing a
      baseline of gene expression in normal cervical tissue is key for identifying
      changes in cancer. We demonstrate the utility of this baseline data by
      identifying genes with aberrant expression in CIN III when compared to normal
      tissue.

PMID- 17543122
TI  - Computational and transcriptional evidence for microRNAs in the honey bee genome.
AB  - BACKGROUND: Non-coding microRNAs (miRNAs) are key regulators of gene expression
      in eukaryotes. Insect miRNAs help regulate the levels of proteins involved with
      development, metabolism, and other life history traits. The recently sequenced
      honey bee genome provides an opportunity to detect novel miRNAs in both this
      species and others, and to begin to infer the roles of miRNAs in honey bee
      development. RESULTS: Three independent computational surveys of the assembled
      honey bee genome identified a total of 65 non-redundant candidate miRNAs, several
      of which appear to have previously unrecognized orthologs in the Drosophila
      genome. A subset of these candidate miRNAs were screened for expression by
      quantitative RT-PCR and/or genome tiling arrays and most predicted miRNAs were
      confirmed as being expressed in at least one honey bee tissue. Interestingly, the
      transcript abundance for several known and novel miRNAs displayed caste or age
      related differences in honey bees. Genes in proximity to miRNAs in the bee genome
      are disproportionately associated with the Gene Ontology terms 'physiological
      process', 'nucleus' and 'response to stress'. CONCLUSION: Computational
      approaches successfully identified miRNAs in the honey bee and indicated
      previously unrecognized miRNAs in the well-studied Drosophila melanogaster genome
      despite the 280 million year distance between these insects. Differentially
      transcribed miRNAs are likely to be involved in regulating honey bee development,
      and arguably in the extreme developmental switch between sterile worker bees and
      highly fertile queens.

PMID- 17543123
TI  - Bilateral male breast cancer with male potential hypogonadism.
AB  - BACKGROUND: Male breast cancer is a comparatively rare disease, and simultaneous
      bilateral male breast cancer is considered to be an extremely rare event. Risk
      factors are said to be genetic factors and hormonal abnormalities due to obesity
      or testicular diseases. CASE PRESENTATION: The patient was a 47-year-old Japanese
      male. His family had no history of female breast cancer. This patient also had
      hypospadias and hormonal examination indicated the presence of primary testicular
      potential hypogonadism, and these hormonal abnormalities seemed to be present
      since childhood or the fetal period. The bilateral breast cancer developed in
      this man at a comparatively young age, and histopathological studies of multiple
      sections showed that there was almost no normal epithelial cell in the ducts,
      while the ducts were almost completely filled with breast cancer cells.
      CONCLUSION: It is thought that male breast cancer is caused by an imbalance
      between estrogen and testosterone. We cannot rule out the possibility that the
      breast cancer developed due to the effect of the slight elevation of estrogen
      over a long period of time, but the actual causative factors in this patient were
      unable to be definitively identified. In the future, we hope to further elucidate
      the causes of male breast cancer.

PMID- 17543124
TI  - Malarial pigment haemozoin, IFN-gamma, TNF-alpha, IL-1beta and LPS do not
      stimulate expression of inducible nitric oxide synthase and production of nitric
      oxide in immuno-purified human monocytes.
AB  - BACKGROUND: Enhanced production of nitric oxide (NO) following upmodulation of
      the inducible isoform of NO synthase (iNOS) by haemozoin (HZ), inflammatory
      cytokines and LPS may provide protection against Plasmodium falciparum malaria by
      killing hepatic and blood forms of parasites and inhibiting the cytoadherence of
      parasitized erythrocytes (RBC) to endothelial cells. Monocytes and macrophages
      are considered to contribute importantly to protective upregulation of iNOS and
      production of NO. Data obtained with murine phagocytes fed with human HZ and
      synthetic HZ (sHZ) indicate that supplemental treatment of those cells with IFN
      gamma elicited significant increases in protein and mRNA expression of iNOS and
      NO production, providing a potential mechanism linking HZ phagocytosis and
      increased production of NO. Purpose of this study was to analyse the effect of P.
      falciparum HZ and sHZ supplemental to treatment with IFN-gamma and/or a
      stimulatory cytokine-LPS mix on iNOS protein and mRNA expression in immuno
      purified human monocytes. METHODS: Adherent immunopurified human monocytes
      (purity >85%), and murine phagocytic cell lines RAW 264.7, N11 and ANA1 were fed
      or not with P. falciparum HZ or sHZ and treated or not with IFN-gamma or a
      stimulatory cytokine-LPS mix. Production of NO was quantified in supernatants,
      iNOS protein and mRNA expression were measured after immunoprecipitation and
      Western blotting and quantitative RT-PCT, respectively. RESULTS: Phagocytosis of
      HZ/sHZ by human monocytes did not increase iNOS protein and mRNA expression and
      NO production either after stimulation by IFN-gamma or the cytokine-LPS mix. By
      contrast, in HZ/sHZ-laden murine macrophages, identical treatment with IFN-gamma
      and the cytokine-LPS mix elicited significant increases in protein and mRNA
      expression of iNOS and NOS metabolites production, in agreement with literature
      data. CONCLUSION: Results indicate that human monocytes fed or not with HZ/sHZ
      were constantly unable to express iNOS and generate NOS metabolites even after
      stimulation with IFN-gamma or a cytokine-LSP mix that were very active on HZ-fed
      murine phagocytic lines. Present data do not support the hypothesis that
      monocytes are mediators of anti-parasitic defence in clinical malaria via
      activation of iNOS and production of NO, and suggest caution in extrapolating
      data obtained with murine or hybrid systems to human malaria.

PMID- 17543126
TI  - An invitation to recent graduates: publish your dissertation/thesis background
      section as a review in Virology Journal.
AB  - Virology Journal will publish background sections of approved dissertations or
      theses as Review Articles.

PMID- 17543125
TI  - Genome Expression Pathway Analysis Tool--analysis and visualization of microarray
      gene expression data under genomic, proteomic and metabolic context.
AB  - BACKGROUND: Regulation of gene expression is relevant to many areas of biology
      and medicine, in the study of treatments, diseases, and developmental stages.
      Microarrays can be used to measure the expression level of thousands of mRNAs at
      the same time, allowing insight into or comparison of different cellular
      conditions. The data derived out of microarray experiments is highly dimensional
      and often noisy, and interpretation of the results can get intricate. Although
      programs for the statistical analysis of microarray data exist, most of them lack
      an integration of analysis results and biological interpretation. RESULTS: We
      have developed GEPAT, Genome Expression Pathway Analysis Tool, offering an
      analysis of gene expression data under genomic, proteomic and metabolic context.
      We provide an integration of statistical methods for data import and data
      analysis together with a biological interpretation for subsets of probes or
      single probes on the chip. GEPAT imports various types of oligonucleotide and
      cDNA array data formats. Different normalization methods can be applied to the
      data, afterwards data annotation is performed. After import, GEPAT offers various
      statistical data analysis methods, as hierarchical, k-means and PCA clustering, a
      linear model based t-test or chromosomal profile comparison. The results of the
      analysis can be interpreted by enrichment of biological terms, pathway analysis
      or interaction networks. Different biological databases are included, to give
      various information for each probe on the chip. GEPAT offers no linear work flow,
      but allows the usage of any subset of probes and samples as a start for a new
      data analysis. GEPAT relies on established data analysis packages, offers a
      modular approach for an easy extension, and can be run on a computer grid to
      allow a large number of users. It is freely available under the LGPL open source
      license for academic and commercial users at http://gepat.sourceforge.net.
      CONCLUSION: GEPAT is a modular, scalable and professional-grade software
      integrating analysis and interpretation of microarray gene expression data. An
      installation available for academic users can be found at
      http://gepat.bioapps.biozentrum.uni-wuerzburg.de.

PMID- 17543127
TI  - An exploratory study of factors that affect the performance and usage of rapid
      diagnostic tests for malaria in the Limpopo Province, South Africa.
AB  - BACKGROUND: Malaria rapid diagnostic tests (RDTs) are relatively simple to
      perform and provide results quickly for making treatment decisions. However, the
      accuracy and application of RDT results depends on several factors such as
      quality of the RDT, storage, transport and end user performance. A cross
      sectional survey to explore factors that affect the performance and use of RDTs
      was conducted in the primary care facilities in South Africa. METHODS: This study
      was conducted in three malaria risk sub-districts of the Limpopo Province, in
      South Africa. Twenty nurses were randomly selected from 17 primary health care
      facilities, three nurses from hospitals serving the study area and 10 other key
      informants, representing the managers of the malaria control programmes, routine
      and research laboratories, were interviewed, using semi-structured
      questionnaires. RESULTS: There was a high degree of efficiency in ordering and
      distribution of RDTs, however only 13/20 (65%) of the health facilities had
      appropriate air-conditioning and monitoring of room temperatures. Sixty percent
      (12/20) of the nurses did not receive any external training on conducting and
      interpreting RDT. Fifty percent of nurses (10/20) reported RDT stock-outs. Only
      3/20 nurses mentioned that they periodically checked quality of RDT. Fifteen
      percent of nurses reported giving antimalarial drugs even if the RDT was
      negative. CONCLUSION: Storage, quality assurance, end user training and use of
      RDT results for clinical decision making in primary care facilities in South
      Africa need to be improved. Further studies of the factors influencing the
      quality control of RDTs, their performance of RDTs and the ways to improve their
      use of RDTs are needed.

PMID- 17543128
TI  - Giant scrotal elephantiasis of inflammatory etiology: a case report.
AB  - BACKGROUND: Scrotal lymphedema is rare outside endemic filariasis regions in
      Africa and Asia. It is of variable origin in the western world. CASE
      PRESENTATION: We present a case of a 40-year-old European man with massive
      elephantiasis of the scrotum attributed to chronic inflammation of the lower
      urinary tract caused by urinary outlet obstruction and diabetes mellitus. The
      patient underwent subtotal scrotectomy saving penis, testes and spermatic cords
      and followed by scrotal reconstruction with adequate cosmetic and functional
      outcome. CONCLUSION: In this report we discuss a rare case of scrotal
      elephantiasis in an European patient, reflect on the etiology and the diagnostic
      and therapeutic approaches. Surgery can be successful even in giant scrotal
      elephantiasis.

PMID- 17543129
TI  - Computerized acoustic assessment of treatment efficacy of nebulized epinephrine
      and albuterol in RSV bronchiolitis.
AB  - AIM: We evaluated the use of computerized quantification of wheezing and crackles
      compared to a clinical score in assessing the effect of inhaled albuterol or
      inhaled epinephrine in infants with RSV bronchiolitis. METHODS: Computerized lung
      sounds analysis with quantification of wheezing and crackles and a clinical score
      were used during a double blind, randomized, controlled nebulized treatment pilot
      study. Infants were randomized to receive a single dose of 1 mgr nebulized l
      epinephrine or 2.5 mgr nebulized albuterol. Computerized quantification of
      wheezing and crackles (PulmoTrack) and a clinical score were performed prior to,
      10 minutes post and 30 minutes post treatment. Results were analyzed with
      Student's t-test for independent samples, Mann-Whitney U test and Wilcoxon test.
      RESULTS: 15 children received albuterol, 12 received epinephrine. The groups were
      identical at baseline. Satisfactory lung sounds recording and analysis was
      achieved in all subjects. There was no significant change in objective
      quantification of wheezes and crackles or in the total clinical scores either
      within the groups or between the groups. There was also no difference in oxygen
      saturation and respiratory distress. CONCLUSION: Computerized lung sound analysis
      is feasible in young infants with RSV bronchiolitis and provides a non-invasive,
      quantitative measure of wheezing and crackles in these infants.

PMID- 17543130
TI  - The impact of splenectomy on outcomes after distal and total pancreatectomy.
AB  - BACKGROUND: Several authors advocate spleen preserving distal pancreatectomy,
      because of the increased complication rate after splenectomy. METHODS:
      Postoperative complications and survival after distal and total pancreatectomy,
      were recorded and retrospectively analyzed according to spleen preservation.
      Patients, who underwent distal and total pancreatectomy without histologically
      proven adenocarcinoma, or extrapancreatic disease, were included in the cohort
      which was divided into splenectomy and no splenectomy groups. Statistical
      analysis was performed using Fisher's test. RESULTS: The study group consisted of
      62 patients who underwent distal and total pancreatectomy between 26/11/1987 to
      6/1/2006. Splenectomy was performed in 35 out of 62 patients (56.5%), distal
      pancreatectomy was performed in 49 out of 62 patients (79%). Morbidity rate was
      28.6% in splenectomy group and 14.8% in the no splenectomy group (p = 0.235),
      while 30 days mortality rate was 2.9%; one patient died in the splenectomy group
      (p = 1). CONCLUSION: Spleen-preservation did not influence the outcomes after
      distal and total pancreatectomy in our series.

PMID- 17543131
TI  - What aspects of periods are most bothersome for women reporting heavy menstrual
      bleeding? Community survey and qualitative study.
AB  - BACKGROUND: Heavy menstrual bleeding is a common symptom amongst women of
      reproductive age, yet questions remain about why some women experience this as a
      problem while others do not. We investigated the concerns of women who reported
      heavy menstrual bleeding on questionnaire. METHODS: A cross-sectional postal
      survey and qualitative interviews were carried out amongst a community-based
      sample of women in Lothian, Scotland. 906 women aged 25 to 44 reported heavy or
      very heavy periods in response to a postal survey of 2833 women registered with
      19 general practices. Amongst those who had reported heavy menstrual bleeding,
      analysis was carried out of responses to the free text questionnaire item, "What
      bothers you most about your periods?" In addition, 32 of these women participated
      in qualitative interviews and their accounts were analysed to explore how
      menstrual symptoms and 'problems' with periods were experienced. RESULTS: Even
      amongst this subgroup of women, selected on the basis of having reported their
      periods as heavy in the survey, pain was the aspect of their periods that 'most
      bothered' them, followed by heaviness, mood changes or tiredness, and
      irregularity or other issues of timing. Interviewees' accounts similarly
      suggested that a range of menstrual symptoms were problematic and some women did
      not disentangle which was worst. Judgements of periods as a problem were based on
      the impact of menstrual symptoms on daily life and this was contingent on social
      circumstances such as type of paid work and other responsibilities. Although
      women spoke readily of whether their periods were a problem, there was less
      clarity in accounts of whether or not menstrual loss was 'heavy'; women said they
      made judgements based on what was normal for them, degree of difficulty in
      containing blood loss and pattern of loss. CONCLUSION: Women with heavy periods
      are bothered by a range of menstrual symptoms and their impact on everyday life.
      Clinical emphasis should be on clarifying the presenting problem and providing
      help and advice for this, as well as on excluding serious disease. Sometimes
      simple approaches, such as help with analgesia, may be all that is required.

PMID- 17543132
TI  - Successful management of elderly breast cancer patients treated without
      radiotherapy.
AB  - BACKGROUND: Breast cancer in the elderly may follow a less aggressive course.
      There are data suggesting that radiotherapy (RT) following breast conserving
      surgery (BCS) for invasive carcinoma may not be necessary in some elderly
      patients. The addition of RT to surgery might constitute an imposition to such
      patients due to age-related factors. The aim of this study was to assess the
      efficacy of BCS without adjuvant RT in this group of patients. PATIENTS AND
      METHODS: A retrospective review of 92 elderly (median age 75 years; range: 70 -
      87 years) patients (analysed as 93 'patients' due to one patient having bilateral
      cancers) managed in a dedicated breast clinic and who underwent BCS for invasive
      carcinoma was carried out. Eighty-three patients did not receive postoperative RT
      to the breast (no-RT group) whereas the remaining 10 had RT (RT-group). RESULTS:
      The median age in this group was 75 (range 70 - 87) years. The mean tumour size
      was 18 mm with a median follow-up of 37 (range 6 - 142) months. In the no RT
      group, adjuvant endocrine therapy with tamoxifen was given to 40/53 patients. No
      patients in the oestrogen receptor (ER) negative group received tamoxifen. The
      local recurrence (LR) rate in this group was 8.4% (2.4% per year, n = 7/83), with
      median time to LR of 17 months. In this no-RT group LR was correlated to ER
      status (2/53 ER+, 5/26ER-, p = 0.024) and margins of excision (n = 1/54 >5 mm,
      2/17 1-5 mm, 4/12 <1 mm, p = 0.001). Within the ER positive group the LR rate was
      0.92% per annum (0.62% per annum in patients treated with adjuvant tamoxifen,
      regardless of margin status). Breast cancer specific survival was correlated to
      histological grade (p < 0.05) and ER status (p < 0.05). CONCLUSION: It would
      appear that omission of RT following successful BCS in elderly patients with ER
      positive tumours receiving adjuvant tamoxifen may be acceptable. The LR rate as
      shown in this retrospective study is highly comparable to that of younger
      patients treated by conventional therapy. This concept is now being evaluated
      prospectively following a change in treatment practice.

PMID- 17543133
TI  - m-Iodosylbenzoic acid - a convenient recyclable reagent for highly efficient
      aromatic iodinations.
AB  - m-Iodosylbenzoic acid performs iodinations of arenes in the presence of iodine at
      room temperature in acetonitrile. Separation of pure products is conveniently
      achieved by scavenging any aryl iodide by ion exchange with IRA-900 (hydroxide
      form). The reduced form of the reagent, m-iodobenzoic acid, can be easily
      recovered from the ion exchange resin or from the basic aqueous solution by
      simple acidification with HCl.

PMID- 17543134
TI  - Beneficial effects of erythropoietin in preclinical models of shock and organ
      failure.
AB  - Erythropoietin protects many organs against the tissue injury and dysfunction
      caused by ischaemia/reperfusion and excessive inflammation. This editorial
      comment discusses the effects of erythropoietin in preclinical models of septic
      shock, endotoxemia, hemorrhagic shock, spinal cord trauma and zymosan-induced
      multiple organ failure.

PMID- 17543135
TI  - Attributable mortality of Acinetobacter baumannii: no longer a controversial
      issue.
AB  - There has been controversy regarding the mortality directly attributed to
      Acinetobacter baumannii infections. Data from six case-control studies have been
      recently added to the literature regarding the attributable mortality of A.
      baumannii infections during the past months. The information from these studies,
      added to the previous knowledge on this issue, provides evidence that A.
      baumannii infections are indeed associated with increased mortality. In addition,
      there is relevant evidence from studies examining the effect of inappropriate
      treatment on mortality; specifically, inappropriate treatment of A. baumannii
      infections has been associated with excess mortality. We believe that the
      accumulated data suggest that attributable mortality due to A. baumannii
      infections should no longer be a controversial issue. The efforts of the
      scientific community interested in this pathogen should therefore be directed to
      the development and introduction of new antibiotics effective against multidrug
      resistant and pandrug-resistant A. baumannii as well as the implementation of
      infection control measures that may help us in the control of the increasing
      problem of A. baumannii infections.

PMID- 17543136
TI  - The integrins.
AB  - The integrins are a superfamily of cell adhesion receptors that bind to
      extracellular matrix ligands, cell-surface ligands, and soluble ligands. They are
      transmembrane alphabeta heterodimers and at least 18 alpha and eight beta
      subunits are known in humans, generating 24 heterodimers. Members of this family
      have been found in mammals, chicken and zebrafish, as well as lower eukaryotes,
      including sponges, the nematode Caenorhabditis elegans (two alpha and one beta
      subunits, generating two integrins) and the fruitfly Drosophila melanogaster
      (five alpha and one beta, generating five integrins). The alpha and beta subunits
      have distinct domain structures, with extracellular domains from each subunit
      contributing to the ligand-binding site of the heterodimer. The sequence arginine
      glycine-aspartic acid (RGD) was identified as a general integrin-binding motif,
      but individual integrins are also specific for particular protein ligands.
      Immunologically important integrin ligands are the intercellular adhesion
      molecules (ICAMs), immunoglobulin superfamily members present on inflamed
      endothelium and antigen-presenting cells. On ligand binding, integrins transduce
      signals into the cell interior; they can also receive intracellular signals that
      regulate their ligand-binding affinity. Here we provide a brief overview that
      concentrates mostly on the organization, structure and function of mammalian
      integrins, which have been more extensively studied than integrins in other
      organisms.

PMID- 17543137
TI  - David against Goliath: may we target and defeat interstitial lung disease in
      systemic sclerosis?

PMID- 17543138
TI  - Ultrasound imaging for the rheumatologist VIII. Ultrasound imaging in
      osteoarthritis.
AB  - The present review provides an update of the available data and discusses
      research issues relating to ultrasound (US) imaging in osteoarthritis (OA).
      Currently, the principal indications for using US in OA include: delineation of
      changes within articular cartilage (AC) and demonstration of synovial and
      adjacent soft tissue pathology together with injection into OA joints under US
      guidance. US has been proposed as a possible imaging tool for following the
      progression of OA. The main priorities requiring the attention of researchers
      include: addressing difficulties surrounding consensus on definitions of
      pathology in OA, charting the natural history of AC change in site specific OA,
      investigation of the link between inflammation and OA and the use of three
      dimensional (3D) US in OA.

PMID- 17543139
TI  - Can we assess baseline pain and global health retrospectively?
AB  - OBJECTIVE: To study the agreement between patients' actual baseline assessments
      of pain and global health before treatment and retrospective assessments
      collected 2 weeks after treatment. METHODS: Data were collected in a prospective
      study of 200 rheumatology outpatients treated with a local corticosteroid
      injection. At baseline and 2-week follow-up, localized pain and global health
      were assessed on 100 mm visual analogue scales. The follow-up questionnaire was
      extended with a retrospective assessment of pain and global health before
      treatment. RESULTS: At follow-up patients slightly overestimated the severity of
      pain and global health before treatment. Actual and retrospective assessments
      were adequately correlated (pain: r(r(r(s) = 0.73; global health: r(s) = 0.67).
      Bland-Altman analysis showed that both pain and global health were characterized
      by high intra-individual variation between actual and retrospective assessments,
      with the 95% limits of agreement (-37.3 to 32.3 mm for pain and -49.7 to 37.8 mm
      for global health) far exceeding proposed values for minimal clinically important
      differences. CONCLUSION: Over a 2-week interval, patients' retrospective
      assessments of baseline pain and global health are fairly accurate and adequately
      correlated with actual baseline scores. At the group level, retrospective
      assessments can provide acceptable data on baseline pain and global health. The
      wide variability between actual and retrospective assessments, however, indicates
      that even over short time intervals there is poor individual agreement between
      the two methods.

PMID- 17543140
TI  - Double-blind, multicenter trial comparing acetyl l-carnitine with placebo in the
      treatment of fibromyalgia patients.
AB  - OBJECTIVE: Fibromyalgia (FMS) is a chronic syndrome characterized by widespread
      pain, troubled sleep, disturbed mood, and fatigue. Several analgesic strategies
      have been evaluated but the results are moderate and inconsistent. Antidepressant
      agents are now considered the treatment of choice in most patients. It has been
      recently suggested that FMS may be associated with metabolic alterations
      including a deficit of carnitine. In this multicenter randomized clinical trial
      we evaluated the efficacy of acetyl L-carnitine (LAC) in patients with overt FMS.
      METHODS: One hundred and two patients meeting the American College of
      Rheumatology criteria for FMS were randomized into the study. The treatment
      consisted of 2 capsules/day of 500 mg LAC or placebo plus one intramuscular
      (i.m.) injection of either 500 mg LAC or placebo for 2 weeks. During the
      following 8 weeks the patients took 3 capsules daily containing either 500 mg LAC
      or placebo. The patients were seen during treatment after 2 (visit 3), 6 (visit
      4) and 10 weeks (visit 5). The patients were also visited 4 weeks after treatment
      discontinuation (follow-up visit). Outcome measures included the number of
      positive tender points, the sum of pain threshold (kg/cm2 or "total myalgic
      score"), the Short Form 36 (SF36), a 100 mm visual analog scale (VAS) for self
      perceived stiffness, fatigue, tiredness on awakening, sleep, work status,
      depression, and muscular-skeletal pain, and the Hamilton depression scale.
      RESULTS: The "total myalgic score" and the number of positive tender points
      declined significantly and equally in both groups until the 6th week of
      treatment. At the 10th week both parameters remained unchanged in the placebo
      group but they continued to improve in the LAC group with a statistically
      significant between-group difference. Most VAS scores significantly improved in
      both groups. A statistically significant between-group difference was observed
      for depression and musculo-skeletal pain. Significantly larger improvements in
      SF36 questionnaire were observed in LAC than in placebo group for most
      parameters. Treatment was well-tolerated. CONCLUSION: Although this experience
      deserves further studies, these results indicate that LAC may be of benefit in
      patients with FMS, providing improvement in pain as well as the general and
      mental health of these patients.

PMID- 17543141
TI  - Life-style activities in systemic lupus erythematosus.
AB  - OBJECTIVE: We evaluated the life-style activities of outpatients with SLE and
      factors that reduce their social activities. METHODS:  SUBJECTS: SLE group = 60
      patients, Control 1 = 30 healthy subjects and Control 2 = 30 patients with other
      autoimmune diseases. The Frenchay Activity Index (FAI), Zung's self-rating
      depression scale (SDS), and the Japanese version of the Philadelphia Geriatric
      Center morale scale-revised (MS) were compared between groups. Relation between
      FAI and age, disease duration, steroid dose, SDS, and MS were examined in the SLE
      group, Control 1, and Control 2. RESULTS: Total scores by FAI was 28.1 +/-8.0
      points in Control 1, whereas it was 26.5 +/- 5.8 points in Control 2 and 24.5 +/-
      7.7 points in the SLE group. While there was no statistical difference between
      the SLE group and Control 2, the scores were significantly lower in the SLE group
      than in Control 1 (P < 0.05). In SLE patients, age, the duration of the disease,
      and the steroid dose had no correlation, but MS had a positive correlation (P <
      0.05) and SDS had a negative correlation (P < 0.05). In Control 2, age, the
      duration of the disease, the steroid dose, MS and SDS had no correlation whereas
      there was significant negative relation between FAI and SDS in Control 1 (r= 
      0.516, P<0.005). CONCLUSION: The significant relation between life-style
      activities and subjective well-being, and depression in SLE suggests that
      detection and treatment of mental status is important in improving the life-style
      activities of SLE patients.

PMID- 17543142
TI  - Cross-cultural adaptation, reliability and validity of the Patient Rated Elbow
      Evaluation (PREE) for German-speaking patients.
AB  - OBJECTIVE: Patient-orientated questionnaires are important instruments for the
      assessment of outcome in the clinical environment and in musculoskeletal
      research. The objective of this study was to cross-culturally adapt the Patient
      Rated Elbow Evaluation (PREE) into German (PREE-G) and to test its reliability,
      validity and psychometric properties. METHODS: The PREE was cross-culturally
      adapted for the German language, according to established guidelines. Fifty-six
      patients who had undergone elbow arthroplasty for osteoarthritis or chronic
      polyarthritis, on average 11 years previously, were assessed using the PREE-G,
      the Short Form 36 (SF-36), the Disabilities of Arm, Shoulder, Hand (DASH) and the
      modified American Shoulder and Elbow Surgeons (mASES) clinical evaluation.
      RESULTS: The test-retest reliability (intraclass correlation coefficient) of the
      PREE-G was 0.80, and the internal consistency 0.96. The PREE-G correlated with
      the DASH (r = 0.73) and the physical component summary of the SF-36 (r = 0.57)
      but not with the mental component summary (r = -0.02). The PREE-G correlated
      moderately with certain clinical findings (mASES) (r = 0.36-0.54; p < 0.01).
      CONCLUSION: The PREE-G represents a reliable and valid instrument to evaluate
      subjective outcome in German speaking patients with elbow pathology.

PMID- 17543143
TI  - Treatment with tiludronate has a similar effect to risedronate on Paget's disease
      activity assessed by bone markers and bone scintigraphy.
AB  - OBJECTIVE: To compare the effects of tiludronate and risedronate on Paget's
      disease activity assessed by biochemical markers of bone turnover and
      quantitative bone scintigraphy. METHODS: An open-labeled non-randomized study was
      performed in 49 patients with Paget's disease who had completed treatment with
      tiludronate (400 mg/d) for 3 months (28 patients) or risedronate (30 mg/d) for 2
      months (21 patients). Biochemical markers of bone turnover, including serum total
      alkaline phosphatase (TAP), bone alkaline phosphatase (BAP), procollagen type I N
      propeptide (PINP) and urinary N-terminal cross-linking telopeptide of type I
      collagen (NTX) were measured at baseline and at 6 and 12 months after the end of
      treatment. Quantitative bone scintigraphy at baseline and 6 months after the end
      of treatment was performed in all patients obtaining a scintigraphic activity
      index (SAI). RESULTS: At baseline there were no significant differences in
      disease activity between both groups of patients, since markers of bone turnover
      as well as SAI were similar in both groups. The effects of tiludronate and
      risedronate in reducing the biochemical markers of bone turnover were comparable
      at 6 months (tiludronate vs risedronate: TAP -52% vs -43%; BAP -69% vs -56%; PINP
      -68% vs -63%; NTX -62% vs -59%) and at 12 months after the end of treatment
      (tiludronate vs risedronate: TAP -47% vs -36%; BAP -57% vs -46%; PINP -57% vs 
      52%; NTX -51% vs -52%). The effects of tiludronate and risedronate on SAI were
      also similar 6 months after the discontinuation of treatment. In addition, the
      percentage of patients who showed normalized serum TAP levels at 6 months after
      treatment were similar with both agents (74% with tiludronate and 70% with
      risedronate). CONCLUSION: Tiludronate and risedronate given at the currently
      recommended dosages induce similar responses in Paget's disease activity.

PMID- 17543144
TI  - Is Taurolidine a candidate for treatment of rheumatoid arthritis?
AB  - OBJECTIVE: To study the therapeutic potential of taurolidine (TRD), a derivative
      of taurine with known anti-inflammatory and anti-proliferative properties, in
      various experimental models of synovitis. METHODS: In vitro: fibroblast-like
      synoviocytes (RA FLS) isolated from the synovial tissue of patients with
      rheumatoid arthritis (RA) were cultured in the presence of either TRD or
      polyvinylpyrrolidine (PVP), the pharmaceutical stabilizer of TRD, which was used
      as a control. Proliferation of RA FLS and cytokine (IL-6 and IL-8) release were
      measured. In vivo: (A). The effect of systemic TRD treatment on the development
      of collagen-induced arthritis (CIA) in female DBA1/J mice was investigated. Mice
      were treated either with intraperitoneal injections of 1 ml of 2% Taurolin
      Boehringer Ingelheim (TRD +PVP) or with PVP as placebo. The incidence of
      arthritis, myeloperoxidase (MPO) activity in periarticular tissue, as well as
      serum concentration of IgG specific to collagen II (IgG alphaCII) were
      determined. (B). The effect of intra-articular TRD treatment was studied in
      rabbits with antigen-induced monoarthritis (AIA). After the induction of AIA of
      right knees rabbits were treated either with intra-articular injections of 0.5 ml
      of 2% Taurolin or 0.5ml PVP ( placebo). The animals were examined for clinical
      signs of arthritis and diameter of joints was measured. After termination of the
      experiment, the arthritic knees were examined and histopathology of the joints
      was assessed. In addition, serum amyloid A (SAA) concentration was measured.
      RESULTS: n vitro: TRD exerted cytotoxic effect on RA FLS when applied at
      concentrations >100 microM. TRD at non-cytotoxic concentrations, inhibited PDGF
      triggered RA FLS proliferation, reduced IL-1beta - stimulated production of IL-6
      and slightly decreased intracellular content of IL-8. In vivo: (A).
      Intraperitoneal treatment with Taurolin significantly reduced the incidence (30%)
      of CIA when compared to the control mice (79%). However, Taurolin failed to
      control the development of CIA in mice with high serum level of IgG alphaCII
      (>1000 U).(B). Intra-articular application of 2% Taurolin resulted in
      amelioration of AIA in all treated rabbits (reduced diameter of arthritic joints
      and smaller rise of SAA level as compared to the control animals).
      Histopathologic evaluation revealed pannus formation in both groups and extensive
      necrotic lesions of synovial tissue treated with TRD, suggesting synoviorthesis
      like effect. CONCLUSION: Results from AIA and from in vitro RA FLS studies
      suggest that intra-articular administration of TRD could be used as a
      "pharmacological scalpel" to remove the inflamed synovium. Our data confirmed
      anti-inflammatory and anti-proliferative properties of TRD in all experimental
      models encouraging further studies which should evaluate its therapeutic
      potential in RA.

PMID- 17543145
TI  - Differential association of HLA-DRB1 alleles in Japanese patients with early
      rheumatoid arthritis in relationship to autoantibodies to cyclic citrullinated
      peptide.
AB  - OBJECTIVE: To evaluate the role of HLA-DRB1 genotypes and antibodies to cyclic
      citrullinated peptides (anti-CCP antibodies) in the development and radiographic
      progression of Japanese patients with rheumatoid arthritis (RA). METHODS: One
      hundred and ten patients with early RA (88 female, 22 male) who visited our
      clinic within 1 year of symptom onset were examined for anti-CCP antibody levels
      and HLA-DRB1 genotypes. HLA-DRB1 genotypes were also determined in 265 healthy
      controls. Radiographic progression over a 2-year interval was evaluated using the
      Larsen's method in 66 patients. RESULTS: Among the 110 patients with early RA, 82
      patients (74.5%) were anti-CCP positive. Carrier frequency of HLA-DRB1*0405 was
      significantly increased in RA patients with anti-CCP antibodies compared with
      controls and RA patients without anti-CCP antibodies (odds ratio [OR] 3.4, 95%
      confidence interval [95% CI] 2.0-5.7 and OR 3.3, 95% CI 1.3-8.6, respectively).
      Carriership of one or two SE alleles was significantly associated with production
      of anti-CCP antibodies (OR 2.7, 95% CI 1.1-6.7 and OR 9.3, 95% CI 1.1-78.2,
      respectively). On the other hand, allele frequency of HLA-DRB1*0901 was
      significantly increased in RA patients without anti-CCP antibodies compared with
      controls and RA patients with anti-CCP antibodies (OR 2.2, 95% CI 1.1-4.1 and OR
      3.0, 95% CI 1.4-6.4, respectively). CONCLUSION: In Japanese patients with RA, HLA
      DRB1 SE alleles are associated with production of anti-CCP antibodies and HLA
      DRB1 alleles appear to be differently associated with early RA depending on anti
      CCP positivity as in Caucasian patients with RA.

PMID- 17543146
TI  - Cytokine patterns in fibromyalgia and their correlation with clinical
      manifestations.
AB  - OBJECTIVE: To examine the possible role of the soluble factor in fibromyalgia
      (FM) by studying the correlation of cytokine levels with the patients' clinical
      and psychiatric profile. METHODS: Eighty FM patients underwent clinical and
      psychiatric evaluations, and plasma levels of cytokines (IL-1, IL-6, IL-8, IL-10,
      TNF-alpha), aspecific markers of inflammation, rheumatoid factor (RF), anti
      extractable nuclear antigen (ENA) antibodies, and anti-nuclear factor (FAN) were
      measured. RESULTS: Higher levels of IL-10, IL-8 and TNF-alpha were found in FM
      patients than in controls. Significant correlations between the biochemical
      parameters and clinical data were found. CONCLUSION: The higher levels of
      cytokines found in FM patients suggest the presence of an inflammatory response
      system (IRS) and highlight a parallel between the clinical symptoms and
      biochemical data. They support the hypothesis that cytokines may play a role in
      the clinical features of fibromyalgia. In addition, the similar cytokine patterns
      found in FM patients with different psychiatric profiles suggests that IRS
      impairment may play a specific role in the disease.

PMID- 17543147
TI  - Prognostic markers of clinical remission in early rheumatoid arthritis after two
      years of DMARDs in a clinical setting.
AB  - OBJECTIVE: To analyze the rate and baseline prognostic factors of clinical
      remission in a series of patients with early rheumatoid arthritis (RA) after 2
      years of therapy based on a structured algorithm using disease-modifying anti
      rheumatic drugs (DMARDs) in a clinical setting. To determine whether a good
      therapeutic response at 6 months of therapy is associated with remission at 2
      years. METHODS: One hundred and five patients (81% female) with early RA (disease
      duration < 2 years) treated with the same therapeutic protocol using gold salts
      and methotrexate in a step-up strategy, together with methylprednisolone (4
      mg/day), were followed up for 2 years. The outcome variable was clinical
      remission after 2 years of DMARD therapy using the 28-joint disease activity
      score (DAS28 < 2.6). Clinical, biological, immunogenetic and radiographic data
      (Larsen score) were analyzed at study entry and after 6, 12, 18 and 24 months of
      follow-up. Therapeutic response was analyzed using the ACR and EULAR criteria.
      RESULTS: Remission was observed in 34 patients (32.4%) after 2 years of follow
      up. A baseline DAS28 score < 5.1 (p = 0.004), hemoglobin (p = 0.04) and male
      gender (p = 0.02) were associated with remission in the univariate analysis. In
      the multivariate logistic regression analysis, only a DAS28 < 5.1 was associated
      with remission at 2 years (OR 4.1, 95% CI: 1.56;10.77, p = 0.004). The percentage
      of ACR50 responses after 6 months was significantly higher in patients with
      remission at 2 years than in those without (66.7% vs 43.3%; p = 0.04). Similar
      results were obtained when analyzing the good EULAR response (50% vs 20.9%; p =
      0.003). Furthermore, when the therapeutic response at 6 months was included in
      the logistic regression model, only an ACR50 response (OR 3.9, 95% CI 1.14;13.38,
      p = 0.03) and a good EULAR response (OR 6.23, 95% CI 1.61; 24.04, p = 0.008), but
      not an ACR20 response or a whole EULAR response were significantly associated
      with remission. CONCLUSION: In a series of early RA patients treated using a
      structured algorithm with DMARDs and very low doses of glucocorticoids, clinical
      remission was observed in one-third of patients after 2 years. Low or moderate
      disease activity (DAS28 < 5.1) at baseline and a good therapeutic response during
      the first months of therapy predicts clinical remission at 2 years.

PMID- 17543148
TI  - Fibroblast-like synoviocyte-chondrocyte interaction in cartilage degradation.
AB  - OBJECTIVE: In vitro models for joint diseases often focus on a single cell type,
      such as chondrocytes in osteoarthritis (OA) or fibroblast-like synoviocytes
      (synoviocytes) in rheumatoid arthritis (RA). However, these joint diseases affect
      the whole joint and interaction between chondrocytes and synoviocytes may play an
      important role in disease pathology. The current study was designed to study the
      use of the alginate recovered chondrocyte method as a model for cartilage
      degradation and to study interaction between chondrocytes and synoviocytes.
      METHODS: Bovine chondrocytes were cultured in alginate beads for 1 week,
      subsequently chondrons were retrieved and seeded into transwells. Every two days
      cartilage-slices were analysed for proteoglycan content (colorimetric, Blyscan
      GAG kit), collagen content (HPLC) and collagen HP and LP crosslinking (HPLC). For
      degradation experiments, monocultures of cartilage-slices labelled with (35)S and
      cocultures with synoviocytes were stimulated with IL-1beta or TNF-alpha. After 7
      days, (35)S release was measured taken as a measure of cartilage degradation.
      RESULTS: After biochemical analysis, three week old cartilage-like slices were
      chosen to perform cartilage-degradation experiments. Synoviocytes were able to
      induce cartilage degradation only in the presence of living chondrocytes. In
      addition, the cytokines interleukin 1 (IL-1beta) and tumor necrosis factor (TNF
      alpha) were only able to induce cartilage degradation by chondrocytes, not by
      synoviocytes. CONCLUSION: These data indicate that the alginate recovered
      chondrocyte method provides a novel model for cartilage degradation in which the
      interaction between synoviocytes and chondrocytes can be studied.

PMID- 17543149
TI  - Treatment of inclusion body myositis with cyclosporin-A or tacrolimus: successful
      long-term management in patients with earlier active disease and concomitant
      autoimmune features.
AB  - OBJECTIVE: Sporadic inclusion body myositis (s-IBM) is a chronic, progressive,
      inflammatory myopathy of unknown aetiology, generally resistant to
      immunosuppressive therapy. Given that lymphocyte infiltrates in s-IBM muscle
      tissue are CD8+ T cells, targeting these cells may represent a valid approach.
      PATIENTS AND METHODS: Three patients with biopsy-proven s-IBM, high creatine
      kinase levels at diagnosis, two of whom with associated immune disorders, were
      treated with either cyclosporin-A (CyA) or tacrolimus, in combination with high
      doses of corticosteroids (CS), followed by rapid CS tapering. Clinical assessment
      and laboratory evaluation were performed every three months for the first year
      and then every six months for the second year. RESULTS: Based on muscle strength
      assessment and muscle enzyme serum levels, a major clinical response was observed
      at month +3 in two out of the three patients. A complete clinical response and
      major clinical response were obtained at month +6, in two and one patient,
      respectively. Normalization of serum muscle enzymes was observed in all. Steroids
      could be tapered to very low doses in all patients and were suspended early in
      one. Laboratory, but not clinical relapse occurred in one patient and was
      controlled by increasing the CyA dose. Treatment was well tolerated, with no
      serious adverse events occurring. All three patients are maintaining
      immunosuppressive therapy. CONCLUSION: Calcineurin inhibitors may represent a
      useful option for the long-term management of s-IBM, possibly in a subset
      characterized by a short duration with high disease activity or associated
      autoimmune manifestations.

PMID- 17543150
TI  - International Classification of Functioning, Disability and Health (ICF) Core Set
      for patients with acute arthritis.
AB  - OBJECTIVE: The aim of this consensus process was to construct a preliminary
      version of the ICF Core Set for acute inflammatory arthritis. METHODS: The
      development of the ICF Core Set involved a formal decision-making and consensus
      process, integrating evidence gathered from preliminary studies including focus
      groups of health professionals, a systematic review of the literature, and
      empiric data collection from patients. RESULTS: Thirty-three experts selected a
      total of 79 second-level categories for the Comprehensive Core Set and 40 second
      level categories for the Brief Core Set. The largest number of categories was
      selected from the ICF component Activities and Participation (28 categories or
      35%). Eighteen (23%) of the categories were selected from the component Body
      Functions, 13 (16%) from the component Body Structures, and 20 (25%) from the
      component Environmental Factors. CONCLUSION: The ICF Core Set for acute arthritis
      is a clinical framework designed to comprehensively assess patients in acute care
      hospitals and early post-acute rehabilitation facilities. This preliminary
      version of the ICF Core Set will be further tested through empiric studies in
      German-speaking countries and internationally.

PMID- 17543151
TI  - Rheumatoid arthritis patients have elevated antibodies to cross-reactive and non
      cross-reactive antigens from Proteus microbes.
AB  - BACKGROUND AND OBJECTIVE: Although a large number of independent studies have
      shown a paramount role for Proteus mirabilis in the aetiopathogenesis of
      rheumatoid arthritis (RA), this hypothesis is still controversial among
      rheumatologists. The main obstacle to its acceptance is the impression that
      increased Proteus antibodies in RA patients is a secondary phenomenon, occurring
      as the result of cross-reactivity between bacterial and self-antigens. To shed
      light on this problem, we examined the link between antibodies to various cross
      reactive and non cross-reactive antigenic peptides from P. mirabilis and analysed
      the relationship between these antibodies and disease severity in patients with
      RA. METHODS: Using the ELISA method, serum samples from 70 RA patients and 20
      healthy controls were screened for total and class-specific antibodies against
      three human cross-reactive and non-crossreactive synthetic peptides from P.
      mirabilis haemolysin, urease C and urease F enzymes. An antibody index, which
      comprised the total concentration of antibodies against these peptides in each
      sample, was correlated with the biochemical parameters of disease activity and/or
      severity, such as the erythrocyte sedimentation rate (ESR), C-reactive protein
      (CRP) and rheumatoid factors (RF). Furthermore, anti-peptide antibody indices
      were evaluated among RA patients with different levels of disease activity as
      defined by ESR and CRP. RESULTS: Significantly elevated levels of total and class
      specific IgG antibodies against the 3 Proteus peptides were observed among RA
      patients compared to healthy controls (p < 0.001). Active RA patients had
      elevated IgM antibodies against all peptides compared to healthy subjects (p <
      0.001). However, no such elevation was observed in IgA anti-peptide antibodies in
      RA patients. A positive correlation was observed between the antibody indices and
      ESR (p < 0.001) and CRP (p < 0.01) concentrations, but not the RF status or
      disease duration. Furthermore, more than 90% of active RA patients showed
      positive values for the Proteus anti-peptide indices. CONCLUSION: The elevated
      levels of antibodies against Proteus antigenic epitopes (which are cross-reactive
      or non cross-reactive with human tissue antigens) observed indicates that this
      enhanced bacterial immune response in RA patients is specifically triggered by
      Proteus microbes. Furthermore, the correlation of anti-peptide antibody indices
      with the biochemical markers of disease activity indicates that these antibodies
      exert damaging cytotoxic effects on joint tissues during the course of the
      disease.

PMID- 17543152
TI  - Antiprothrombin antibodies: a comparative analysis of homemade and commercial
      methods. A collaborative study by the Forum Interdisciplinare per la Ricerca
      nelle Malattie Autoimmuni (FIRMA).
AB  - OBJECTIVE: Prothrombin (PT) is a target for antibodies with lupus anticoagulant
      (LA) activity, suggesting the possible application of anti-prothrombin antibody
      (aPT) assays in patients with antiphospholipid syndrome (APS). Different methods 
      both homemade and commercial - for the detection of aPT are available, but they
      seem to produce conflicting results. The purpose of this study was to compare the
      performance of different assays on a set of well-characterized serum samples.
      PATIENTS AND METHODS: Sera were gathered from 4 FIRMA institutions, and
      distributed to 15 participating centres. Forty-five samples were from patients
      positive for LA and/or anticardiolipin antibodies (aCL) with or without APS, and
      15 were from rheumatoid arthritis (RA) patients negative for antiphospholipid
      antibodies. The samples were evaluated for IgG and IgM antibodies using a
      homemade direct aPT assay (method 1), a homemade phosphatidylserine-dependent aPT
      assay (aPS/PT, method 2), and two different commercial kits (methods 3 and 4). In
      addition, a commercial kit for the detection of IgG-A-M aPT (method 5) was used.
      RESULTS: Inter-laboratory results for the 5 methods were not always comparable
      when different methods were used. Good inter-assay concordance was found for IgG
      antibodies evaluated using methods 1, 3, and 4 (Cohen k > 0.4), while the IgM
      results were discordant between assays. In patients with thrombosis and pregnancy
      losses, method 5 performed better than the others. CONCLUSION: While aPT and
      aPS/PT assays could be of interest from a clinical perspective, their routine
      performance cannot yet be recommended because of problems connected with the
      reproducibility and interpretation of the results.

PMID- 17543153
TI  - The relationship of disease duration to foot function, pain and disability in
      rheumatoid arthritis patients with foot complaints.
AB  - OBJECTIVE: To assess the relationship between disease duration and foot function
      (expressed as pressure and gait parameters), foot pain and disability, in
      patients with foot complaints secondary to rheumatoid arthritis (RA). METHODS:
      Sixty-two patients with RA-related foot complaints were included. Disease
      duration was defined as the time since RA was diagnosed. A pressure platform was
      used to measure both pressure parameters (i.e. pressure-time integrals and peak
      pressures in the forefoot) and gait parameters (i.e. total loading time and
      loading time in different foot regions). In addition, measurements of foot pain,
      disability (i.e. walking time and self reported disability), forefoot joint
      damage and disease activity were obtained. Data were analysed using partial
      correlations (Spearman), correcting for age. RESULTS: Disease duration was
      significantly correlated with the maximum pressure-time integral (PTI) measured
      under the forefoot (r = 0.330, p = 0.01). Disease duration was also significantly
      correlated with gait parameters, i.e. total loading time (r = 0.265, p = 0.04),
      duration of heel loading and duration of toe loading (r = 0.326, p = 0.01 and r =
      -0.288, p = 0.03 respectively), and walking time (r = 0.297, p = 0.02). Disease
      duration did not correlate with self-reported foot pain or disability.
      CONCLUSION: In patients with RA-related foot complaints, longer disease duration
      is associated with impaired foot function and reduced walking speed. These
      findings are interpreted as an alteration in pressure distribution and gait
      pattern during the course of disease, with a shift from a heel-to-toe roll-over
      process to a more shuffling gait.

PMID- 17543154
TI  - Increased serum levels of nitrotyrosine, a marker for peroxynitrite production,
      in systemic sclerosis.
AB  - OBJECTIVE: To determine serum levels of nitrotyrosine (NT), an end product of
      peroxynitrite (ONOO-), and its clinical association in patients with systemic
      sclerosis (SSc). METHODS: Serum NT levels from 25 patients with limited cutaneous
      SSc (lSSc) and 34 patients with diffuse cutaneous SSc (dSSc) were examined by
      enzyme-linked immunosorbent assay. RESULTS: Serum NT levels were elevated in SSc
      patients compared with normal controls (n = 27), the levels being similar between
      lSSc and dSSc patients (P < 0.001). SSc patients with elevated NT had higher
      serum levels of anti- agalactosyl IgG Ab, IgG and IgA than those with normal NT
      levels (P < 0.05). NT levels correlated inversely with the percentage diffusion
      capacity for carbon monoxide (DLco) (P < 0.02, r = -0.414, n = 47). CONCLUSION:
      These results suggest that ONOO- may play an important role in the clinical
      manifestations of SSc, especially vascular damage to the lungs, and that ONOO-
      may be related to immunological abnormalities in SSc.

PMID- 17543155
TI  - A pilot study of mycophenolate mofetil combined to intravenous methylprednisolone
      pulses and oral low-dose glucocorticoids in severe early systemic sclerosis.
AB  - OBJECTIVE: This pilot study was aimed at evaluating the efficacy and safety of a
      protocol-based treatment strategy combining mycophenolate mofetil (MMF),
      intravenous (IV) methylprednisolone (MP) pulses and low-dose glucocorticoids (GC)
      in early systemic sclerosis (SSc) patients suffering from either active
      interstitial lung disease (ILD) or extensive skin disease. PATIENTS AND METHODS:
      Sixteen SSc patients were recruited in the study, 9 based on the severity of
      their skin involvement (modified Rodnan total skin score [TSS] >or= 15) and 7
      based on the presence of active ILD. Patients received 3 consecutive daily IV MP
      pulses, followed by 5 additional monthly IV MP pulses. MMF (0.5 g bid for one
      week; then, 1 g bid) and low-dose (5-10 mg/day) oral prednisolone were prescribed
      for one year. Patients were assessed at baseline, month 6 and 12. Statistics were
      by ANOVA. RESULTS: TSS and Health Assessment Questionnaire significantly improved
      over time. In ILD patients, the vital capacity, forced expiratory volume in one
      second and carbon monoxide diffusing capacity significantly improved. Although
      the difference was not statistically significant, ground glass lesions decreased,
      based on semi-quantitative planimetry analyses performed on chest high-resolution
      computerized tomography. Toxicity was low and none of the patients suffered from
      renal crisis. CONCLUSION: The results of this pilot study suggest that the
      combination of MMF, IV MP and low-dose GC might achieve good clinical, functional
      and radiological results in patients suffering from severe early SSc.

PMID- 17543156
TI  - Intravenous cyclophosphamide for interstitial lung disease associated to systemic
      sclerosis: results with an 18-month long protocol including a maintenance phase.
AB  - OBJECTIVE: Cyclophosphamide (CYC) is generally considered the most promising
      agent available today for systemic sclerosis (SSc)-related interstitial lung
      disease (ILD). However, the optimal dosage and length of treatment are still
      undetermined. Our objective was to evaluate the effect of an 18-month long
      protocol with intravenous (iv) CYC. METHODS: In a single-centre, prospective,
      observational study, 13 patients with SSc and active alveolitis were given 8 iv
      pulses in a 6-months period (CYC 750 mg + 6-methylprednisolone 125 mg every three
      weeks), as an induction therapy. Patients received maintenance therapy with
      further cycles at 4 (3 pulses), 6 (3 pulses) and 9 weeks (3 pulses) interval.
      Total CYC dosage was 12.75 g in an 18-month period. End-points were modifications
      of lung function test (LFT). RESULTS: During the first 6 months of treatment with
      CYC an increase in Forced Vital Capacity (FVC; p = 0.005) and in diffusion lung
      capacity for carbon monoxide (DLCO; p = 0.10) was observed; during the
      maintenance therapy, there was a stabilization in FVC and a mild, non significant
      decline in DLCO. Treatment was well tolerated. CONCLUSION: iv CYC can induce an
      initial improvement in LFT (particularly, in FVC) in the first six months, but no
      further improvement was observed during the maintenance phase.

PMID- 17543157
TI  - Frequency of recent parvovirus infection in patients examined for acute reactive
      arthritis. A study with combinatorial parvovirus serodiagnostics.
AB  - OBJECTIVE: To determine the causative role of human parvovirus B19 as a preceding
      infection in patients examined for acute reactive arthritis (ReA). METHODS: Sixty
      adult patients with acute arthritis were screened for evidence of triggering
      infections. In all patients, cultures of stool specimens and of Chlamydia
      trachomatis in urethra/cervix, and/or bacterial serology were studied. The timing
      of primary infection of human parvovirus B19 was determined by measurement in
      serum of VP2-IgM, VP2-IgG, epitope-type specifity of VP2-IgG, and avidity of VP1
      IgG. RESULTS: Median time from onset of joint symptoms to the rheumatological
      consultation was five weeks (range 1-62). Of the 60 patients, 35 fulfilled the
      diagnostic criteria for ReA; in the remaining, the diagnosis was unspecified
      arthritis (UA). Thirty-six patients had antibodies for the B19 virus. Occurrence
      of these antibodies did not differ significantly between ReA and UA groups (P =
      0.61). Of these 36 patients, 34 had a pre-existing immunity to the B19 virus. Of
      the two other patients, one had rash and self-limiting polyarthritis with
      serological evidence of B19 primary infection, and the other had arthritis of the
      lower extremities with serological evidence of a convalescence period after the
      B19 primary infection. The latter patient also had antibodies to Yersinia, with a
      clinical picture typical for ReA. CONCLUSION: In patients examined for acute ReA,
      the frequency of recent B19 virus infection was 3.3% (2 out of 60). The
      diagnostic utility of the presented methodology, by using a single serum sample,
      was evident.

PMID- 17543158
TI  - Advanced magnetic resonance imaging of the brain in patients treated with TNF
      alpha blocking agents.
AB  - OBJECTIVE: Neurological symptoms have been reported in patients treated with anti
      TNF-alpha. In a pilot study we evaluated the effect of anti-TNF-alpha on cerebral
      parenchyma using advanced Magnetic Resonance (MR) techniques. METHODS: Seven
      patients with a systemic inflammatory disease (5 rheumatoid arthritis, 2
      psoriatic arthritis) had Magnetization Transfer Imaging, Diffusion Weighted
      Imaging (DWI) and Magnetic Resonance Spectroscopy (MRS) of the brain before and
      after administration of anti-TNF-alpha. Four patients were neuropsychologically
      evaluated. RESULTS: After treatment with TNF-alpha blocking agents the
      Magnetization Transfer Ratio histogram Peak-heights (MTR-Pht) of the white and
      gray matter decreased (p < 0.01 and p < 0.05 respectively). The Apparent
      Diffusion Coefficient for the white and gray matter and the metabolite ratios in
      the centrum semiovale did not significantly change after therapy.
      Neuropsychological assessment showed no difference before and after anti-TNF
      alpha. CONCLUSION: The decrease of the MTR-Pht after anti-TNF-alpha therapy
      suggests loss of parenchyma integrity; however, these changes could not be
      attributed to inflammation or demyelination based on our complementary DWI and
      MRS data. The decrease of the MTR-Pht did not result in decreased cognitive
      function.

PMID- 17543159
TI  - Vascular endothelial growth factor in patients with psoriatic arthritis.
AB  - OBJECTIVE: To determine the levels of vascular endothelial growth factor (VEGF)
      in patients with active psoriatic arthritis, patients with inactive psoriatic
      arthritis, and healthy controls. Serum VEGF levels were correlated with clinical
      and laboratory features in patients with active psoriasis arthritis. METHODS:
      Serum samples from 14 patients with active psoriatic arthritis, 14 patients with
      inactive psoriatic arthritis, and 9 healthy controls were investigated. VEGF
      levels in the serum were measured using a sensitive sandwich ELISA. RESULTS: The
      mean serum VEGF concentration in patients with active PA was 394.4 pg/ml (394 +/-
      171.8), in patients with inactive PA 200.4 pg/ml (200.4 +/- 115.7), and in
      healthy subjects 214.3 pg/ml (214.3 +/- 162.1). Patients with active psoriasis
      arthritis had significantly higher levels of VEGF compared to patients with
      inactive psoriasis arthritis and healthy individuals (p > 0.001). In contrast,
      VEGF levels were comparable in patients with inactive psoriatic arthritis and
      controls (p =0.659). Furthermore, in patients with psoriatic arthritis, VEGF
      levels were positively correlated with ESR, HAQ, PASI and VAS. CONCLUSION: VEGF
      levels may be regarded as a good indicator of active psoriasis arthritis.

PMID- 17543160
TI  - Unusual association between pure red cell aplasia and primary Sjogren's syndrome:
      a case report.
AB  - Pure red cell aplasia (PRCA) is an acute anemia due to selective suppression of
      erythropoiesis. We report a case of PRCA diagnosed before the onset of primary
      Sjogren's syndrome (SS). A young woman, with autoimmune thyroiditis, developed
      polyarthritis with ANA and Rheumatoid factor positivity, diagnosed as Rheumatoid
      arthritis. During the time she developed anti-Ro and anti-La antibodies and
      deformities at proximal interphalangeal joints. After 4 years, she developed
      severe acute anemia, without reticolocytes: a bone marrow biopsy indicated a PRCA
      and she started transfusions, steroids, cyclosporin. A steroid-dependent anemia
      persisted. After 2 years she developed sicca, parotid swelling, fatigue, mild
      leukopenia, elevated serum creatinine, hypokalemia, hyposthenuria and tubular
      proteinuria. Lip biopsy and dacriologic tests confirmed a diagnosis of SS, while
      X-ray revealed a deforming non-erosive arthropathy (Jaccoud type). In present
      case, PRCA could be considered an autoimmune bone marrow disease within SS, whose
      extra-glandular manifestations onset before the sicca symptoms.

PMID- 17543161
TI  - Dermatopathic lymphadenopathy in a patient with adult onset Still's disease.
AB  - Adult onset Still's disease (AOSD) is a systemic inflammatory disorder of unknown
      cause characterized by high fever accompanied by systemic manifestations. Since
      AOSD consists of heterogeneous symptoms and has no definite diagnostic tool, the
      diagnosis is based upon exclusive criteria. Dermatopathic lymphadenopathy (DL) is
      characterized by a localized paracortical proliferation of histiocytes and
      deposition of melanin in the lymph nodes. DL is not only a reactive hyperplasia
      of the lymph nodes, but has also been reported to be associated with
      hematological malignancies such as cutaneous T cell lymphoma (CTCL) and Hodgkin's
      lymphoma. It is therefore important to evaluate CTCL or Hodgkin's lymphoma in a
      patient with DL, in order to both rule out hematological malignancy and diagnose
      AOSD. In this report, we first describe a 37-year-old patient with AOSD whose
      biopsy of lymph node was proved to be DL.

PMID- 17543162
TI  - En coup de sabre accompanied by pachydermoperiostosis: a case report.
AB  - Scleroderma en coup de sabre, a variant of localized scleroderma is a disorder
      characterized by fibrosis of connective tissue. We report a 21-year-old female
      with scleroderma en coup de sabre accompanied by pachydermoperiostosis. She was
      born to consanguineous parents and her older sister also had
      pachydermoperiostosis characterized by clubbing of the digits, enlargement of
      distal parts of the extremities. The two disorders were diagnosed by clinical
      examination, histological and x-ray findings. In contrast to scleroderma,
      pachydermoperiostosis is a hypertrophic process characterized by periosteal
      proliferation of the tubuler bones and hypertrophic skin changes. We discuss this
      interesting coexistence and review the literature.

PMID- 17543163
TI  - B-cell: a logical target for treatment of rheumatoid arthritis.
AB  - The interest for B-cells in rheumatoid arthritis (RA) is currently being revived.
      They are involved in the development and activation of lymphoid architecture by
      regulating dentritic cell and T-cell function through cytokine production.
      Receptor editing an revising are also essential in B-cells and aid in preventing
      autoimmunity. Abnormalities in the subset distribution and a default in any task
      assigned to the B-cells may favor autoimmunity. Beneficied responses to B-cell
      depletion in RA by anti-CD20 monoclonal antibody rituximab illustrate the
      importance of B-lymphocytes in the pathogenesis of this disease. A new avenue has
      thus been opened, whereby B-lymphocytes return as a significant contributor to
      autoimmune disorders.

PMID- 17543164
TI  - Corticosteroid-induced osteoporosis in children: outcome after two-year follow
      up, risk factors, densitometric predictive cut-off values for vertebral
      fractures.
AB  - OBJECTIVE: To identify factors that contribute to a decreased Z score of
      volumetric spine bone mineral density (ZvSBMD) and the development of vertebral
      fractures (VF) in children receiving chronic systemic corticosteroid therapy
      (SCT); to describe their outcome after 2 years, and to define predictive
      threshold values for ZvSBMD for VF. METHODS: Fifty-five children on SCT for >or=
      6 months were prospectively followed for 2 years. In children with a ZvSBMD > 
      1.5, we prescribed preventive measures for osteoporosis and densitometry
      annually. In children with ZvSBMD <or= -1.5, we prescribed spine x-rays and those
      with VF received alendronate. The association between clinical and biochemical
      variables and the presence of VF or ZvSBMD were analyzed by logistic regression
      or multiple regression analysis. The threshold value of ZvSBMD for predicting VF
      was determined by ROC curve and the probability of having a VF was modeled by
      multiple logistic regressions. RESULTS: Children who do not develop osteoporosis
      at first evaluation tend to maintain normal ZvSBMD after two years. Alendronate
      increased ZvSBM (median: at baseline: -2.69; 1 yr: -1.92; 2 years: -1.39, p <
      0.001). The threshold value of ZvSBMD for predicting VF was -1.8. In this cohort,
      the risk of developing VF was significantly higher in children who were not
      ambulatory, growth retarded, treated with methotrexate for a longer time, had a
      family history of osteoporosis or were of non-aboriginal ancestry. CONCLUSION:
      Children on SCT, who do not develop osteoporosis, tend to maintain normal BMD.
      Children who were not ambulatory, on methotrexate or growth retarded have higher
      rates of VF.

PMID- 17543165
TI  - X-linked chronic granulomatous disease (CGD) caused by an intra-exonic splice
      mutation (CYBB exon 3, c.262G->A) is mimicking juvenile sarcoidosis.
AB  - BACKGROUND: Chronic granulomatous disease (CGD) is caused by mutations in genes
      encoding nicotinamide dinucleotide phosphate (NADPH) oxidase subunits. CASE
      REPORT: A boy was diagnosed as having juvenile sarcoidosis because he presented
      with cervical and pulmonary lymphadenopathy with epitheloid cells and granuloma
      formation and high angiotensin converting enzyme. Later, a liver abscess was
      diagnosed. CGD was established by a dihydrorhodamine 123 (DHR) assay and genetic
      analysis revealed an unusual intra-exonic splice mutation in the CYBB gene
      encoding gp91-phox. It did not change the amino acid sequence and allowed for
      residual NADPH oxidase activity explaining the late onset of the disease.
      CONCLUSION: CGD is an important differential diagnosis of juvenile sarcoidosis.

PMID- 17543166
TI  - A clinical case of drug hypersensivity syndrome with phenobarbital
      administration: drug-induced rash with eosinophilia and systemic symptoms or
      lupus-like syndrome?

PMID- 17543167
TI  - Can neridronate be effective in the treatment of osteoporosis in hypogonadic men?

PMID- 17543168
TI  - Glaucomatous type abnormalities in patients with systemic sclerosis.

PMID- 17543169
TI  - Remitting seronegative symmetrical synovitis with pitting edema (RS3PE): a
      paraneoplastic syndrome? A new case.

PMID- 17543170
TI  - Interstitial pneumonia in adult-onset Still's disease.

PMID- 17543171
TI  - Maternal and fetal outcome of pamidronate treatment before conception: a case
      report.

PMID- 17543172
TI  - Early onset neutropenia after rituximab in lupus nephritis.

PMID- 17543173
TI  - Endothelial cell chimerism by fluorescence in situ hybridization in gender
      mismatched renal allograft biopsies.
AB  - BACKGROUND: The blood vessels of a transplanted organ are the interface between
      donor and recipient. The endothelium in the blood vessels is thought to be the
      major target for graft rejection. Endothelial cells of a transplanted organ can
      be of recipient origin after transplantation. In this study, we tested whether
      endothelial chimerism correlated with the graft rejection and cold ischemia.
      METHODS: We studied the biopsy samples from 34 renal transplants of female
      recipients who received the kidney from a male donor for the presence of
      endothelial cells of recipient origin. We examined the tissue sections of renal
      biopsy samples by fluorescence in situ hybridization (FISH) for the presence of
      endothelial cells containing two X chromosomes using a biotinylated Y chromosome
      probe and digoxigenin labelled X chromosome probe, and then analyzed the
      relationship between the endothelial cell chimerism and the rejection and cold
      ischemia. RESULTS: Endothelial chimerism was common and irrespective of
      rejections (P > 0.05). The cold ischemic time of chimerism group was longer than
      no chimerism group ((14.83 +/- 4.03) hours vs (11.27 +/- 3.87) hours, P < 0.05).
      CONCLUSIONS: There is no correlation between the percentage of recipient
      endothelial cells in vascular endothelial cells and the type of graft rejection.
      The endothelium damaged by ischemic injury might be repaired by the endothelial
      cells from the recipient.

PMID- 17543174
TI  - Firebird sirolimus eluting stent versus bare mental stent in patients with ST
      segment elevation myocardial infarction.
AB  - BACKGROUND: There are few evidences about the value of drug eluting stent in
      patients with ST-segment elevation myocardial infarction (STEMI). We
      prospectively designed a randomized controlled trial to compare the safety and
      efficacy of Firebird sirolimus eluting stent (Firebird stent) and bare metal
      stent (BMS). METHODS: Patients with STEMI enrolled during one year period were
      randomized to undergo implantation of Firebird stent or BMS, and clinical and
      angiographic follow-up. The primary endpoint of the present study was in-lesion
      late lumen loss (LLL) at 6 months, and secondary endpoint includes stent
      thrombosis and major adverse cardiac events (MACE) at 6 months. RESULTS: During
      one year period, 156 patients were randomized into the Firebird stent group (101
      patients with an average age of 57.8 years) or the BMS group (55 patients with
      59.7 years on average). Six-month angiographic follow-up was available in 66.3%
      and 63.7% of patients assigned to Firebird stent and BMS, respectively. At 6
      month follow-up, mortality, target vessel revascularization (TVR) and MACE were
      2.0%, 6.9% and 9.9% in the Firebird stent group, while 3.6%, 30.9% and 36.4% in
      the BMS group (P < 0.05). Subacute thrombosis occurred in 1 patient in both
      groups, respectively. The mean LLL was 0.18 mm in the Firebird stent group versus
      0.72 mm in the BMS group. CONCLUSION: Implantation of Firebird sirolimus eluting
      stent for STEMI may greatly reduce TVR and MACE at 6 months with low incidence of
      acute/subacute stent thrombosis compared with BMS.

PMID- 17543175
TI  - Relation of supplementary feeding to resumptions of menstruation and ovulation in
      lactating postpartum women.
AB  - BACKGROUND: Resumption of menstrual cycles is one of the indicators for
      restoration of reproductive capability in postpartum women. However, menstruation
      does not necessarily mean that ovulation has taken place. The aim of this study
      was to investigate the relation of supplementary feeding to return of
      menstruation and ovulation after delivery. METHODS: A questionnaire was used to
      obtain data from 101 breastfeeding mothers. The following elements were analyzed:
      age, education level, breastfeeding practice, time of return of menstruation,
      contraceptive practice, and starting time of supplementary feeding during the
      lactation at intervals of 6 weeks to 18 months after delivery. The ovulation was
      continuously monitored by ultrasonography and basal body temperature (BBT)
      measurement. RESULTS: By ultrasonography, 53 of the 101 women (52.5%) had the
      first ovulation (follicle > 1.8 cm in diameter) within 154 days after delivery on
      average, among whom 11 (10.9%, 11/101) had restoration of ovulation within 4
      months and 42 (41.6%, 42/101) had it after 4 months. In women with follicles >
      1.8 cm in diameter (n = 53), the menstruation resumed (138 +/- 84) days after
      delivery, and the supplementary feeding was started at (4.0 +/- 1.1) months,
      which were significantly earlier than those in the women with follicular diameter
      < 1.7 cm (n = 48; (293 +/- 88) days, (5.1 +/- 1.3) months; t = 9.003, P < 0.01
      and t = 4.566, P < 0.01). In the women with follicles < 1.8 cm in diameter, 30
      had return of menstruation before the end of ultrasonographic monitoring, while
      only 8 in the women with follicular diameter < 1.7 cm had menstrual resumption at
      the same time (chi(2) = 16.91, P < 0.01). The starting time of supplementary
      feeding was positively correlated with the time of the restoration of
      menstruation (n = 100, r = 0.4764, P < 0.01) and first ovulation after delivery
      (n = 53, r = 0.5554, P < 0.01). In this series, no woman had pregnancy within 18
      months postpartum. CONCLUSION: Supplementary feeding can affect the restoration
      of menstrual cycles and ovulation in lactating postpartum women.

PMID- 17543176
TI  - Plasma resistin is increased in patients with unstable angina.
AB  - BACKGROUND: Resistin, a novel adipokine linked to insulin resistance and obesity
      in rodents, which is derived mainly from macrophages and identified in atheromas
      in human, has been shown to play a potential role in atherosclerosis. Resistin
      levels were reported to increase in coronary artery disease (CAD), while data
      concerning resistin in different stages of CAD in Chinese people are lacking. The
      aim of this study was to assess whether plasma concentrations of resistin
      differed between patients with unstable and stable angina pectoris. METHODS:
      Plasma resistin levels were determined by means of enzyme-linked immunosorbent
      assay (ELISA) in 46 patients with unstable angina (UAP), 37 with stable angina
      (SAP) and 31 control subjects. RESULTS: Plasma concentrations of resistin were
      significantly increased in UAP group (geometric mean (interquartile range) 12.09
      ng/ml (8.40, 18.08)) in comparison with SAP (9.04 ng/ml (7.09, 11.44)) and
      control groups (8.71 ng/ml (6.58, 11.56)). No differences in resistin levels were
      found between patients with SAP and controls. We also found that plasma resistin
      positively correlated with leukocyte counts (r = 0.21, P = 0.027), high sensitive
      C-reactive protein (hs-CRP) (r = 0.25, P = 0.008), and endothelin-1 (r = 0.21, P
      = 0.025) after adjustment for age, sex and BMI. CONCLUSION: Resistin may be
      involved in the development of CAD by influencing systemic inflammation and
      endothelial activation.

PMID- 17543177
TI  - Contrast sensitivity and higher-order aberrations in patients with astigmatism.
AB  - BACKGROUND: Astigmatism is one of the most significant obstacles for achieving
      satisfactory visual function. This study was to evaluate the influence of
      astigmatism on contrast sensitivity (CS) and higher-order aberrations. METHODS:
      CS, accommodation response and wavefront aberration were measured in 113 patients
      with astigmatism, aged 18 - 36 years. Both single and binocular visual
      performance were examined under four lighting conditions: photopia, photopia with
      glare, scotopia and scotopia with glare respectively. Accommodation response was
      classified as normal, abnormal and low. The contribution of the power and axis of
      astigmatism to CS, accommodation response and wavefront aberration was analyzed.
      RESULTS: As the dioptric power of astigmatism increased, the loss of CS spatial
      frequency changed from high to intermediate, and then to low frequency. CS scores
      varied at different illuminance levels, descending in the following sequence:
      photopia, photopia with glare, scotopia, and scotopia with glare. However, the
      normal accommodation group showed better CS values under photopia with glare than
      without glare. The range of influenced direction of sine-wave gratings remained
      mostly at the meridian line of high dioptric power, which would be expanded when
      optical accommadation attenuated. The patients with symmetrical astigmatism got
      higher CS scores with binoculus vision than with dominant eye vision, while the
      patients with asymmetrical astigmatism did this only at scotopia with glare.
      Among higher-order aberrations, coma aberration, secondary coma aberration and
      the total higher order aberration were influenced by astigmatism, all of which
      rising with the power of astigmatism increased. CONCLUSIONS: Reducing astigmatism
      might improve the performance of visual function. Not only the power of
      astigmatism should be cut down, but also the binocular axes should be made
      symmetrically.

PMID- 17543178
TI  - Opposite effects of WEB2086 on angiogenesis in atheromas and ischemic hindlimb of
      apoE gene deficient mice.
AB  - BACKGROUND: Our previous research has suggested that platelet activating factor
      receptor was related to atherosclerosis. The present study investigated the
      effect of a platelet activating factor receptor antagonist-WEB2086 on
      angiogenesis in aortal plaque and ischemic hindlimb of apolipoprotein E-deficient
      mice. METHODS: Eight-week-old apolipoprotein E-deficient mice were fed with a
      0.15% cholesterol diet to develop advanced lesions. At age 32 weeks unilateral
      hindlimb ischemia was surgically induced and the mice were divided into two
      groups: with or without WEB2086 mixed with their drinking water (4.3 mg in 100
      ml). At age 40 weeks blood was collected from the orbit for measurement of serum
      lipids and an enzyme linked immunosorbent assay was used to determine platelet
      activating factor and oxidized low density lipoprotein in the gastrocnemius and
      aorta. Whole-Mount CD31 stain and plaque-associated sprouting have been used to
      estimate angiogenesis in plaque from the aorta and laser Doppler perfusion
      imaging and immunohistochemical expression of von Willebrand factor have been
      used to estimate angiogenesis in ischemic hindlimb. RESULTS: The lipid
      composition of serum was not different between the groups. However, the amount of
      platelet activating factor and oxidized low density lipoprotein detected in the
      aorta was significantly higher than that in the gastrocnemius of ischemic
      hindlimb. The ratio of lesion to aorta levels was significantly reduced by
      administration of WEB2086, (31.52 +/- 6.18)% vs (55.58 +/- 8.34)%, P < 0.01. The
      mean density of intimal capillaries in atherosclerotic plaque, (31.13 +/- 9.20)%
      vs (57.74 +/- 11.28)%, P < 0.01, and the mean number of sprouts per aorta were
      significantly reduced, 183.92 +/- 34.17 vs 392.54 +/- 76.79, P < 0.01, in the
      WEB2086 group. Blood flow (0.85 +/- 0.12 vs 0.45 +/- 0.06, P < 0.01) and
      capillary density of ischemic hindlimb (1.18 +/- 0.17 vs 0.53 +/- 0.09, P < 0.01)
      were markedly increased in apolipoprotein E-deficient mice treated with WEB2086
      versus controls. CONCLUSION: The study provides evidence that WEB2086 can inhibit
      angiogenesis in atherosclerotic plaque but promote it in ischemic hindlimb.

PMID- 17543179
TI  - Expression profiles and function of Toll-like receptors in human corneal
      epithelia.
AB  - BACKGROUND: Toll-like receptors play an important role in the human immune
      system. This study was conducted to investigate the expression profiles and
      function of Toll-like receptor (TLR) 1 - 9 in human corneal epithelium. METHODS:
      The expression of TLR1 - 9 mRNA in 20 human donor corneal epithelia samples
      abraded during photorefractive keratotomy (PRK) and cultivated telomerase
      immortalized human corneal epithelial cells (THCEs) was examined by semi
      quantitative reverse-transcriptase polymerase chain reaction (RT-PCR) analysis.
      Human peripheral blood mononuclear cells (PBMCs) were used as positive controls.
      The expression of the TLR2 and TLR4 proteins was detected by Western analysis.
      ELISA was used to detect IL-8 secretion from THCEs challenged with ligands for
      TLR3 and TLR4 with and without antibody blockade. RESULTS: The expression of TLR1
      - 9 at the mRNA level was detected in the epithelia of 20 patients and in THCE.
      Significant differences among individuals were observed. One patient was found to
      lack of the expression of TLR3, 4, 6 and 8, whereas another did not express TLR5.
      The expression of TLR2 and TLR4 protein was detected in human corneal epithelial
      cells. As THCE cells express TLR1 - 9, cells were challenged with
      lipopolysaccharides (LPS) and poly I:C to determine whether TLR4 and TLR3 were
      functional. The results showed that secretion of IL-8 by cells stimulated with
      LPS and Poly I:C was 7 to 10 fold greater than secretion by unchallenged cells.
      Blocking TLR4 with an anti-TLR4 antibody significantly inhibited the LPS-induced
      IL-8 production by THCE (P < 0.05). CONCLUSION: Human corneal epithelial cells
      express multiple TLRs and are able to recognize LPS and poly I:C. Different
      expression profiles among individuals suggest that differences in the
      susceptibilities and sensitivities to bacterial and viral infection in human
      populations relate to different patterns of TLR expression.

PMID- 17543180
TI  - Earthworm fibrinolytic enzyme: anti-tumor activity on human hepatoma cells in
      vitro and in vivo.
AB  - BACKGROUND: The earthworm fibrinolytic enzyme (EFE) is a complex protein enzyme
      that is widely distributed in the earthworm's digestive cavity. Possessing strong
      protein hydrolysis activity, EFE not only has a direct effect on fibrin, but also
      can activate plasminogen. Its therapeutic and preventative effects on thrombosis
      related disease have been confirmed clinically. Recently, there has been
      increased interest in the anti-tumor activity of EFE. In this study, the anti
      tumor activity of EFE, isolated from Eisenia foetida, on human hepatoma cells was
      evaluated in vitro and in vivo. The potential mechanisms involved were also
      studied. METHODS: In vitro experiments were performed in four human hepatoma cell
      lines: HLE, Huh7, PLC/PRF/5 and HepG2. After treatment with EFE in various
      concentrations, the inhibition of the rate of cell proliferation was measured.
      For the in vivo studies, tumor-bearing models xenografted with Huh7 cells were
      developed in nude mice, and then the mice were fed with EFE once a day for 4
      weeks, and the control group received only saline. An inhibitory effect on tumor
      growth was observed. Also, apoptosis was observed with flow cytometric assay and
      fluorescent dye staining with acridine orange and ethidium bromide (AO/EB). The
      expression of matrix metalloproteinase 2 (MMP-2) were detected by Western
      blotting assay. RESULTS: After treatment with various concentrations of EFE, the
      proliferation of all hepatoma cell lines was suppressed to varying degrees in
      vitro. The IC(50) for HLE, Huh7, PLC/PCF/5 and HepG2 were 2.11, 5.87, 25.29 and
      17.30 uku/ml, respectively. After administration of EFE orally for 4 weeks, the
      growth of tumor xenograft of Huh7 cells in nude mice was significantly inhibited
      in vivo. The tumor inhibitory rates in the EFE 500 uku/(kgxd) and 1000 uku/(kgxd)
      groups were 46.08% (compared with control group, P = 0.026) and 57.52% (compared
      with control group, P = 0.002) respectively. Meanwhile, the average weight of
      body, spleen or thymus did not show any remarkable differences among the various
      groups. The population in sub-G(1) stage was more in the EFE treated groups than
      in the control group according to flow cytometric assay. After treatment with EFE
      0, 5, 10 uku/ml for 72 hours, the apoptotic rates were 3.5%, 10.9% and 12.3% in
      HLE cells, and 5.0%, 24.7% and 34.5% in Huh7 cells respectively. Under
      fluorescent staining with AO/EB, the apoptotic morphological changes could be
      detected more significantly in the EFE treated groups than in the untreated
      groups. After treatment with EFE in doses of 0, 5, 10 uku/ml for 72 hours, the
      apoptotic rates were 3.02%, 8.76%, 10.54% in HLE cells, and 3.95%, 18.27%, 30.89%
      in Huh7 cells respectively. The apoptosis-inducing effects of EFE occurred in a
      dose dependent manner. Western blotting assay showed that, after treatment with
      EFE, the secretions of MMP-2 were significantly inhibited in HLE and Huh7 cells.
      CONCLUSIONS: EFE showed significant anti-tumor activity in hepatoma cells both in
      vitro and in vivo, which may be because EFE could induce apoptosis of hepatoma
      cells and inhibit the expression of MMP-2. This suggests that EFE has a potential
      role in the treatment of hepatoma.

PMID- 17543181
TI  - Overexpression of cyclin L2 induces apoptosis and cell-cycle arrest in human lung
      cancer cells.
AB  - BACKGROUND: Uncontrolled cell division is one of the hallmarks of tumor growth.
      Researches have been focused on numerous molecules involved in this process.
      Cyclins are critical regulatory proteins of cell cycle progression and/or
      transcription. The present study aimed to investigate the anti-proliferative
      effect of cyclin L2, and to define its growth regulatory mechanisms using human
      lung adenocarcinoma cell line A549. METHODS: Human cyclin L2 was transfected into
      human lung adenocarcinoma cells (A549 cell), and was expressed in a mammalian
      expression vector pcDNA3.1. The effects and mechanisms of the cyclin L2 in cell
      growth, cell cycle analysis and apoptosis were studied by 3-(4,5-dimethylthiazol
      2-yl)-2, 5-diphenyltetrazolium bromide (MTT), flow cytometry or Western blot,
      respectively. RESULTS: Overexpression of cyclin L2 inhibited the growth of A549
      cells. Cell cycle analysis in cells transfected with pCCNL2 revealed an increment
      in proportion in G0/G1 phase ((68.07 +/- 4.2)%) in contrast to (60.39 +/- 2.82)%
      of the cells transfected with mock vector. Apoptosis occurred in (7.25 +/- 0.98)%
      cells transfected with pCCNL2, as compared with (1.25 +/- 0.21)% of the mock
      vector control group. Cyclin L2-induced-G0/G1 arrest and apoptosis involved
      upregulation of caspase-3 and downregulation of Bcl-2 and survivin. CONCLUSION:
      The results indicate that overexpression of cyclin L2 protein may promote
      efficient growth inhibition of human lung adenocarcinoma cells by inducing G0/G1
      cell cycle arrest and apoptosis.

PMID- 17543182
TI  - Mediating effect of dopamine D3 receptors on Jak2 and GABAAalpha1 expression in
      mouse brains induced by cocaine.
AB  - BACKGROUND: Cocaine addiction may involve complex neuroadaptations, including
      many changes of genes expression. Dopamine D3 receptors play an important role in
      cocaine addiction; however, its role in cocaine induced gene expression change is
      poorly understood. To identify the changes in gene expression induced by repeated
      cocaine exposure through D3 dopamine receptors, we compared the expression of
      four molecules: Janus kinase 2 (Jak2), g-aminobutanoic acid receptor subunit
      alpha 1 (GABAAalpha1), glutamate receptor AMPA3 alpha 3 (GluR 3) and stromal cell
      derived factor 1 (SDF1). These four have been implicated in mediating the actions
      of cocaine in the nucleus accumbens (NAc) and caudoputamen (CPu) in mice after
      acute and repeated cocaine exposure. METHODS: For the acute and repeated
      injections, the mice were divided into four groups: 30 mg/kg cocaine, nafadotride
      0.5 mg/kg + cocaine 30 mg/kg, nafadotride 0.5 mg/kg, and saline as the basal
      group. The expression of Jak2, GABAAalpha1, GluR 3 and SDF1 were assayed by
      Western blot, quantitative real-time RT-PCR and immunohistochemistry. RESULTS:
      Twenty-four hours after seven consecutive days of repeated cocaine exposure, the
      expression of GABAAalpha1 decreased in cocaine group compared with basal line and
      further decreased in the cocaine + nafadotride group and remained at basal level
      in the nafadotride group. Similarly, the Jak2 expression decreased in cocaine
      group compared with base line. However, the levels of Jak2 increased in cocaine +
      nafadotride group compared with cocaine group, while remained at basal level in
      nafadotride group. CONCLUSIONS: GABAAalpha1 and Jak2 may be involved in chronic
      cocaine induced neuroadaptations. D3 dopamine receptors play an important role in
      the expression of these genes.

PMID- 17543183
TI  - Glycine receptors contribute to cytoprotection of glycine in myocardial cells.
AB  - BACKGROUND: The classic glycine receptor (GlyR) in the central nervous system is
      a ligand-gated membrane-spanning ion channel. Recent studies have provided
      evidence for the existence of GlyR in endothelial cells, renal proximal tubular
      cells and most leukocytes. In contrast, no evidence for GlyR in myocardial cells
      has been found so far. Our recent researches have showed that glycine could
      protect myocardial cells from the damage induced by lipopolysaccharide (LPS).
      Further studies suggest that myocardial cells could contain GlyR or binding site
      of glycine. METHODS: In isolated rat heart damaged by LPS, the myocardial
      monophasic action potential (MAP), the heart rate (HR), the myocardial tension
      and the activities of lactate dehydrogenase (LDH) from the coronary effluent were
      determined. The concentration of intracellular free calcium ([Ca(2+)](i)) was
      measured in cardiomyocytes injured by LPS and by hypoxia/reoxygenation (H/R),
      which excludes the possibility that reduced calcium influx because of LPS
      neutralized by glycine. Immunohistochemistry was used to detect the GlyR in
      myocardial tissue. GlyR and its subunit in the purified cultured cardiomyocytes
      were identified by Western blotting. RESULTS: Although significant improvement in
      the MAP/MAPD(20), HR, and reduction in LDH release were observed in glycine + LPS
      hearts, myocardial tension did not recover. Further studies demonstrated that
      glycine could prevent rat mycordial cells from LPS and hypoxia/reoxygenation
      injury (no endotoxin) by attenuating calcium influx. Immunohistochemistry
      exhibited a positive green-fluorescence signaling along the cardiac muscle
      fibers. Western blotting shows that the purified cultured cardiomyocytes express
      GlyR beta subunit, but GlyR alpha1 subunit could not be detected. CONCLUSIONS:
      The results suggest that glycine receptor is expressed in cardiomyocytes and
      participates in cytoprotection from LPS and hypoxia/reoxygenation injury. Glycine
      could directly activate GlyR on the cardiomyocytes and prevent calcium influx
      into the cardiomyocytes.

PMID- 17543184
TI  - Pharmacological action and mechanisms of ginkgolide B.
AB  - OBJECTIVE: To review the recent research progress in pharmacological actions and
      mechanisms of ginkgolide B. Data sources Information included in this article was
      identified by searching of PUBMED (1987 - 2006) online resources using the key
      terms "ginkgolide B", "platelet activating factor", and "pharmacological". Study
      selection Mainly original milestone articles and critical reviews written by
      major pioneer investigators of the field were selected. RESULTS: The key issues
      related to the pharmacological actions and mechanisms of ginkgolide B were
      summarized. The ginkgolide B possesses a number of beneficial effects such as
      anti-inflammatory, anti-allergic, antioxidant, and neuroprotective effects.
      Meantime, their mechaniams were discussed. CONCLUSIONS: The Ginkgolide B is the
      most potent antagonist of platelet activating factor (PAF) and exhibits
      therapeutic action in a variety of diseases mainly by the PAF receptor.

PMID- 17543185
TI  - Changes in the intestinal microflora of children with Helicobacter pylori
      infection and after Helicobacter pylori eradication therapy.

PMID- 17543186
TI  - A comparison of retroperitoneoscopic and open surgical renal pedicle lymphatic
      disconnection for the treatment of serious filarial chyluria.

PMID- 17543187
TI  - Aortic stent graft infection in a patient with Marfan syndrome.

PMID- 17543188
TI  - Imaging diagnosis of two unusual forms of gallstone ileus.

PMID- 17543189
TI  - A 9-year-old Chinese boy with Alagille syndrome.

PMID- 17543190
TI  - Giant congenital cerebriform pigmented nevus of scalp: case report.

PMID- 17543192
TI  - Selectivity among dipeptidyl peptidases of the S9b family.
AB  - Dipeptidyl peptidase IV is a serine protease with an indirect role in
      antihyperglycaemia via degradation of the incretin hormones glucagon-like peptide
      1 and glucose-dependent insulinotropic polypeptide. Inhibition of the DPP-IV is
      thus a potential therapeutic strategy for type 2 diabetes. In this study, we have
      investigated upon selectivity of dipeptidyl peptidase IV compared to two other
      members of the S9b family, dipeptidyl peptidase 8 and 9, based on kinetic
      analyses of the pancreatic peptide hormones neuropeptide Y and peptide YY. We
      report a striking 250-fold preference for cleavage of neuropeptide Y compared to
      peptide YY observed for DPP-8/-9, but not for DPP-IV. This difference appears to
      be linked to differences in the S1' pocket within the active site, particularly
      via flexibility of the oxyanion stabilizing residue Y547. These aspects are
      discussed in relation to available protein structures of DPP-IV and data on DPP
      IV selective inhibitors.

PMID- 17543193
TI  - Hydrogen peroxide activation of endothelial cell-associated MMPs during VCAM-1
      dependent leukocyte migration.
AB  - Leukocyte migration from the blood into tissues is vital for immune surveillance
      and inflammation. Specificity for the site of leukocyte migration is determined
      by the combination and concentration of adhesion molecules, cytokines and
      chemokines in the microenvironment. Leukocytes bound at sites of extravasation
      migrate within minutes. We have focused on the function of the adhesion molecule
      VCAM-1 and have reported an active function for the endothelium during VCAM- 1
      dependent leukocyte migration. VCAM-1 activates endothelial cell NADPH oxidase
      followed by the generation of 1 microM H2O2. This stimulates endothelial cell
      associated matrix metalloproteinase (MMP) activity in minutes, consistent with
      the time for lymphocyte migration. The endothelial cell NADPH oxidase and
      endothelial cell MMP activities are required for VCAM-1-dependent lymphocyte
      migration as determined by scavenging of ROS, by pharmacologic or antisense
      inhibition of NADPH oxidase and by pharmacologic inhibition of endothelial cell
      MMPs. Furthermore, antioxidants block VCAM-1 activation of MMPs. In vivo,
      administration of the antioxidant bilirubin blocks VCAM-1-dependent leukocyte
      migration into the lung in experimental asthma. In summary, endothelial cells are
      not simply a scaffold for leukocyte adhesion. Instead, endothelial cells have an
      active function during VCAM-1-dependent leukocyte transendothelial migration.

PMID- 17543194
TI  - Poison-antidote systems in bacteria: the co-evolution of functional counterparts.
AB  - Bacterial pathogens secrete a multitude of factors, many of which exhibit
      enzymatic activity that is directed against host-specific targets or are
      activated by host-specific functions. To counter these toxic molecules, producing
      organisms have developed several mechanisms in order to protect themselves
      against enzymes that have the ability to adversely affect both the microbe and
      the host cell. Potentially toxic molecules are strictly controlled by several
      strategies often involving a functional counterpart. Through the work of
      ourselves and others it has recently become apparent that certain bacterial
      extracellular proteases require inhibition by dedicated intracellular inhibitors
      in order that they may function only in their specific niche and cause no harm to
      the producing cell. Thus, it is our contention that these protease-inhibitor
      couplings represent a fascinating example of functional co-evolution, and are
      analogous to the protective mechanisms observed with the toxin-antitoxin
      pairings, and other such protective systems discussed within this review.

PMID- 17543195
TI  - Inorganic polyphosphate stimulates lon-mediated proteolysis of nucleoid proteins
      in Escherichia coli.
AB  - Inorganic polyphosphate (polyP) accumulates in response to amino acid starvation
      in Escherichia coli. Previously, we found that the complex formation of Lon with
      polyP stimulates proteolysis of free ribosomal proteins. In the current studies,
      we examined the effects of polyP on the degradation of major nucleoid proteins.
      Fusions of green fluorescent protein with HimA, Fis, HupA, and HupB were clearly
      associated with polyP in vivo. Lon degraded His-tagged HimA protein only in the
      presence of polyP in vitro as well as in vivo. Whereas, when HimA and HimD formed
      a heterodimer, Lon could not degrade it even in the presence of polyP. In
      addition, Lon degraded His-tagged Fis protein in the presence of polyP. However,
      in vivo, Lon did not efficiently degrade the Fis protein even when cells
      accumulated polyP in response to amino acid starvation. It appears that this is
      due to tighter binding of Fis to DNA than to polyP and resistance of the DNA-Fis
      to Lon-mediated proteolysis. Indeed, we found that at least a five-fold excess of
      polyP was necessary to displace DNA from the DNA-Fis complex. Furthermore, Lon
      degraded His-tagged HupA protein efficiently in the presence of polyP. We also
      showed that degradation of the translational initiation factor InfC depends on
      polyP.

PMID- 17543196
TI  - Some unusual manifestations of proteolysis.
AB  - In the article the results of the long-term researches revealing the essence of
      the following three phenomena are generalized. 1. Participation of active oxygen
      species (especially, superoxide radical) in activation of zymogens--plasminogen,
      trypsinogen, chymotrypsinogen, pepsinogen and in realization of the catalytic
      (proteolytic) function of a number of proteinases. The essence of the hypothesis
      of oxygen-dependent reactions of proteolysis is stated. As shown by the example
      of mouse brain homogenate fractions, the plasminogen-activating ability of the
      fractions can also be realized via this way. From the positions of these views
      the experimental facts obtained about the influence of streptokinase and
      plasminogen on vital activity of nervous tissue cells are analysed. 2.
      Suppression of proteolytic reactions by ATP: plasminogen-activating ability of
      streptokinase, gamma- and betasubunits of the nerve growth factor, proteolytic
      activity of Arthrobothrys longa proteinases, destroyed cells of Corynebacterium
      diphtheriae PW-8. In some cases a significant effect was reached at concentration
      of ATP < or = 0.001 M. The effect depends on protein substrates used. 3. The
      increase of fibrinolytic activity of the mitochondrial fraction of the mouse
      brain and liver, proteolytic activity of human lymphoblasts of transplanted lines
      in the presence of inorganic orthophosphate. Judging by the results of inhibitory
      analysis, it is not caused by the resynthesis of ATP in the system and has an
      independent character--"phosphate effect" in proteolysis. 4. The results of our
      researches of formation of stable equimolar complexes of streptokinase or
      plasminogen with enzymes of carbohydrate-energetic metabolism are briefly
      analysed. The results of researches of functional properties of the molecules of
      diphtheria toxin, the nerve growth factor and it subunits are summarized. A
      number of fundamental and applied consequences of these phenomena are considered.

PMID- 17543197
TI  - Proteinase dysbalance in pathology: the neprilysin (NEP) and angiotensin
      converting enzyme (ACE) families.
AB  - Proteolytic enzymes constitute some 2% of the human genome and provide important
      therapeutic targets in many diseases. The identification of many novel proteases
      from genome sequencing programmes provides both qualitative and quantitative
      challenges to target identification and validation. Some approaches to dealing
      with these questions and addressing functional correlates of proteolytic activity
      at the level of molecular cell biology are provided in this review focusing on
      two spheres of interest: neurodegeneration and cardiovascular regulation. The
      role and regulation of the neprilysin (NEP) family of metalloproteinases is
      highlighted in particular in the context of proteolytic events underlying the
      pathology of Alzheimer's disease. The second exemplar involves the newly
      appreciated complexity of the renin-angiotensin system as a regulator of the
      cardiovascular system. The application of functional genomics approaches to the
      discovery of angiotensin-converting enzyme-2 (ACE2) as a counterbalance to the
      well known hypertensive target ACE will be highlighted and their differential
      cellular targeting and enzymology addressed. Finally, the serendipitous discovery
      of ACE2 as the SARS virus receptor illustrates the surprises always in store from
      nature.

PMID- 17543199
TI  - The correlation of homocysteine-thiolactonase activity of the paraoxonase (PON1)
      protein with coronary heart disease status.
AB  - Homocysteine (Hcy)-thiolactonase (HTase) activity of the paraoxonase-1 (PON1)
      protein detoxifies Hcythiolactone in human blood and could thus delay the
      development of atherosclerosis. We investigated a hypothesis that HTase activity
      is associated with coronary heart disease. We studied HTase activities and PON1
      genotypes in a group of 475 subjects, 42.5% of whom were healthy and 57.5% had
      coronary heart disease (CHD). We found that HTase activity was positively
      correlated with total cholesterol (r=0.254, P<0.0001), LDL cholesterol (0.149,
      P=0.016), ApoB (r=0.167, P=0.006), ApoA1 (0.140, P=0.023), and HDL cholesterol
      (0.184, P=0.002) in a group of CHD cases (n=270) but not in controls (n=202).
      Mean HTase activity was significantly higher in CHD cases than in controls (4.57
      units vs. 3.30 units, P <10(-5)). The frequencies of the PON1-192 genotypes in
      CHD cases were similar to those in controls. HTase activity was not different
      between patients receiving statins and those not treated with statins. Multiple
      regression analysis shows that CHD status, PON1 genotype, and total cholesterol
      are determinants of HTase activity in humans. Our results suggest that HTase
      activity of the PON 1 protein is a predictor of CHD.

PMID- 17543200
TI  - How dietary deficiency, genes and a toxin can cooperate to produce
      arteriosclerosis and ischemic heart disease.
AB  - Four classes of agents capable of producing human illness have been identified:
      toxicity, heredity, infection and deficiency. Examples of how members of these
      classes of etiologic agents can cooperate to produce illness were shown. The
      copper deficiency theory of ischemic heart disease and the homocysteine theory of
      arteriosclerosis were examined using concepts about cooperation. The Western diet
      so closely associated with these illnesses often is low in copper. Copper
      deficiency decreases the activity of methionine synthase which contributes to
      elevation of homocysteine, and of paraoxonase which impairs hydrolysis of
      homocysteine thiolactone, an inhibitor of lysyl oxidase. This copper-dependent
      enzyme initiates the cross-linking of collagen and elastin in arteries and bone.
      High homocysteine also impairs superoxide dismutase, a copper-dependent enzyme
      important in oxidative defense. Some genes affecting paraoxonase activity may
      respond to dietary copper. The copper deficiency theory of ischemic heart disease
      and the homocysteine theory of arteriosclerosis are inextricably entwined.

PMID- 17543201
TI  - Priorities in the discovery of the implications of water channels in epilepsy and
      Duchenne muscular dystrophy.
AB  - Folate and vitamin B12 are essential cofactors for the methionine/homocysteine
      cycle in the brain. These vitamins mediate the remethylation of homocysteine
      (HCY), which affects the production of the universal methyl donor, S
      adenosylmethionine (SAM), in the brain among other organs. Acquired or inherited
      disorders in these metabolic pathways are associated with brain abnormalities and
      severe neurological symptoms that are mostly irreversible, even after providing
      the missing cofactors. This review discusses the relationship between brain and
      blood levels of key vitamins and metabolites related to one carbon metabolism.

PMID- 17543202
TI  - Ciglitazone ameliorates homocysteine-mediated mitochondrial translocation and
      matrix metalloproteinase-9 activation in endothelial cells by inducing peroxisome
      proliferator activated receptor-gamma activity.
AB  - The activation of peroxisome proliferator activated receptor-gamma (PPARgamma)
      ameliorates the homocysteine (Hcy)-induced matrix metalloproteinase (MMP) by
      decreasing reactive oxygen species (ROS) production. However, the mechanism by
      which Hcy induces ROS generation and MMP activation is unclear. We hypothesize
      that Hcy increases NADH oxidase (Nox-4) and decreases thioredoxin (Trx). This
      leads to translocation of Nox-4 into the mitochondria and decrease in Trx. In
      addition, activation of PPARgamma ameliorates the translocation of Nox-4 into
      mitochondria and MMP-9 activation. Mouse aortic vascular endothelial cells (MVEC)
      were cultured in the presence or absence of 100 microM Hcy. The cells were pre
      treated with ciglitazone (CZ, 150 microM). Activity of PPARgamma activity was
      measured by electrophoretic mobility shift assay (EMSA) and antibody super shift
      assay. In situ generation of ROS was measured using 2,7-dichlorofluorescin (DCF)
      as a probe. The expression of Nox-4 and Trx were measured by quantitative real
      time polymerase chain reaction (Q-RT-PCR). The translocation of Nox-4 was
      measured by 2-D gel analysis. To determine the levels of Nox-4 and Trx, the
      mitochondria and cytosol were separated and Western blot analysis was preformed.
      The MMP-9 activity was measured by gelatin-zymography. The results suggested that
      CZ activated endothelial PPARgamma in the presence of Hcy. Production of ROS was
      ameliorated by PPARgamma activation. Expression of Nox-4 was increased, while
      production of Trx was decreased by Hcy. However, the treatment with CZ normalized
      the levels of Nox-4 and Trx. Nox-4 was translocated into mitochondria in Hcy
      treated endothelial cells. This translocation was associated with decreased
      production of Trx in mitochondria. The treatment with CZ blocked this
      translocation and increased Trx levels in mitochondria. Hcy-mediated MMP-9
      activity was decreased in cells pre-treated with CZ. These results suggest that
      Hcy increases NADH oxidase and decreases Trx by translocation of Nox-4 to
      mitochondria. The data show that indeed, activation of PPARgamma ameliorates the
      mitochondrial translocation of NOX-4 and MMP-9 activation.

PMID- 17543204
TI  - Ontology-based lymphocyte population description using mathematical morphology on
      colour blood images.
AB  - Despite modern technologies (immunophenotyping, molecular probing, etc.)
      cytomorphologic examination of stained peripheral blood smears by microscopy
      remains the main way of diagnosis in a large variety of diseases (e.g. leukaemic
      disorders). Using tools from mathematical morphology for processing peripheral
      blood colour images, we have developed an image-based approach, to provide an
      objective and understandable description of lymphocyte populations according to a
      specifically designed ontology. This ontology-based framework needs a
      conceptualisation of the problem from a morphological viewpoint, the introduction
      of an adapted language, the generation of representative image databases, the
      development of image processing and data classification algorithms to automate
      the procedure and the validation of the system by human expertise. In this paper
      we present the main concepts, algorithms and some results to illustrate the high
      performance of the approach. The aim of our work is to reconcile the
      automatisation with the medical expertise, so that they can reinforce each other.

PMID- 17543205
TI  - The increasing influence of medical image processing in clinical neuroimaging.
AB  - This paper review the evolution of clinical neuroinformatics domain in the passed
      and gives an outlook how this research field will evolve in clinical neurology
      (e.g. Epilepsy, Multiple Sclerosis, Dementia) and neurosurgery (e.g. image guided
      surgery, intra-operative imaging, the definition of the Operation Room of the
      future). These different issues, as addressed by the VisAGeS research team, are
      discussed in more details and the benefits of a close collaboration between
      clinical scientists (radiologist, neurologist and neurosurgeon) and computer
      scientists are shown to give adequate answers to the series of problems which
      needs to be solved for a more effective use of medical images in clinical
      neurosciences.

PMID- 17543206
TI  - ADN-Viewer: a 3D approach for bioinformatic analyses of large DNA sequences.
AB  - Most of biologists work on textual DNA sequences that are limited to the linear
      representation of DNA. In this paper, we address the potential offered by Virtual
      Reality for 3D modeling and immersive visualization of large genomic sequences.
      The representation of the 3D structure of naked DNA allows biologists to observe
      and analyze genomes in an interactive way at different levels. We developed a
      powerful software platform that provides a new point of view for sequences
      analysis: ADNViewer. Nevertheless, a classical eukaryotic chromosome of 40
      million base pairs requires about 6 Gbytes of 3D data. In order to manage these
      huge amounts of data in real-time, we designed various scene management
      algorithms and immersive human-computer interaction for user-friendly data
      exploration. In addition, one bioinformatics study scenario is proposed.

PMID- 17543207
TI  - An automatic system for the analysis of intercellular communication and early
      carcinogenesis.
AB  - Some recent works on intercellular communication pointed out an impaired
      trafficking of Cx43 proteins in early carcinogenesis. In collaboration with
      biologists, we propose an automatic system for the analysis of spatial protein
      configurations within cells at early tumor stages. This system is an essential
      step towards the future development of a computer-aided diagnosis tool and the
      statistical validation of biological hypotheses about Cx43 expressions and
      configurations during tumorogenesis. The proposed system contains two dependent
      part: a segmentation part in which the cell structures of interest are
      automatically located on images and a characterization part in which some spatial
      features are computed for the classification of cells. Using immunofluorescent
      images of cells, the nucleus, cytoplasm and proteins structures within the cell
      are extracted. Then, some spatial features are computed to characterize spatial
      configurations of the proteins with regard to the nucleus and cytoplasm areas in
      the image. Last, the 3D cell images are classified into pathogenic or viable
      classes. The system has been quantitatively evaluated over 60 cell images
      acquired by a deconvolution high-resolution microscope and whose ground truth has
      been manually given by a biologist expert. As a perspective, a 3D spatial
      reasoning and visualization module is currently under development.

PMID- 17543208
TI  - Statistical approach to boar semen evaluation using intracellular intensity
      distribution of head images.
AB  - We propose a method for the classification of boar sperm heads based on their
      intracellular intensity distributions observed in microscopic images. The image
      pre-processing comprises segmentation of cell heads and normalization for
      brightness, contrast and size. Next, we define a model distribution of head
      intracellular intensity of an alive cell using a set of head images assumed to be
      alive by veterinary experts. We now consider two other sets of cell head images,
      one formed by heads assumed to be alive by experts and another formed by cells
      which present some abnormalities in their cytoplasm densities and are considered
      as dead by the experts. We define a measure of deviation from the model intensity
      distribution and for each head image of the two test sets we compute the
      deviation from the model. While the distributions of deviation values for alive
      and dead cells overlap, it is possible to choose an optimal value of a decision
      criterion for single cell classification in such a way that the error made in the
      estimation of the fraction of alive cells in a sample is minimal. In the range
      [0.7,1.0] of interesting values of the fraction of alive cells, the standard
      deviation of the fraction estimation error for samples of 100 head images is
      smaller than 0.04. Thus, in 95% of the cases the value of the fraction of alive
      cells in a sample estimated by a veterinary expert will be within 8% of the
      estimation made according to the proposed method. This result satisfies the
      requirements of veterinary practice.

PMID- 17543209
TI  - Intrinsic 2D/3D registration based on a hybrid approach: use in the radiosurgical
      imaging process.
AB  - During the latest years, numerous methods of multimodal image matching have been
      developed. Associated with medical imaging, these developments make it possible
      to match images using intrinsic data, as anatomical data, instead of external
      referential, as stereotactic frames. Thus, the use of intrinsic registration
      considerably increases possibilities in medical image analysis. Unfortunately,
      these techniques mostly remain in the research field and are rarely used in
      clinical daily practice. In this paper, we present a method for matching
      projective imaging (2D, radiography, angiography...) and tomographic imaging (3D,
      Magnetic Resonance Imaging, Computed Tomography). Furthermore, we propose a
      radiosurgical application for Arteriovenous Malformation (AVM). Radiosurgery
      planning for the treatment of AVM requires multiple image acquisitions in
      multimodality to define the irradiation target and to compute the dosimetry. All
      the planning images are acquired with a stereotactic frame. We describe in this
      paper the image registration technique that we propose to include diagnostic
      images in the planning process and the different steps required to validate our
      approach. In the current state, the results obtained do not enable us to replace
      the conventional technique due to the accuracy expected, but the analysis of the
      results shows that improvements of the protocol would make this application
      finally operational.

PMID- 17543210
TI  - Quantitative videomicroscopic analysis of the sociologic behavior of non-invasive
      and invasive tumor cell lines.
AB  - To analyze the spatial distribution of tumor cell lines with different invasive
      properties, we used time-lapse videomicroscopic recordings associated with
      software programs we have developed for quantification. We observed that non
      invasive tumor cells rapidly formed small clusters which aggregated to form
      larger clusters, whereas highly invasive tumor cells remained isolated and did
      not form clusters. An attraction index computed from a cellular automaton model
      was used to quantify the degree of attraction-repulsion between cells. The
      results suggest that the cluster formation by noninvasive cells is not related to
      a global attraction model and that the random (dispersed) distribution of
      invasive cells is not related to cell repulsion. According to these results, we
      can conclude that random cell movement combined with the intrinsic properties of
      cells explains the phenomenon of cluster formation.

PMID- 17543211
TI  - Color image retrieval: from low-level representation to high-level concept.
AB  - This work takes place within the framework of color image retrieval in
      specialized databases. A CBIR scheme has been proposed allowing to use a
      description thanks to low-level features in the framework of a high-level concept
      using a knowledge management. Starting from a representation of the three most
      frequently used features i.e. color, texture and shape, cooperation techniques
      are proposed in order to use the expert knowledge in the combination process. Two
      types of cooperation have been defined; the first is without categorization and
      the second with categorization. The second approach allows to make a selection of
      the query category in order to simplify queries in large image databases.
      Finally, in order to avoid the standard relevance feedback stage, a competition
      technique has been proposed allowing an unsupervised refinement of the submitted
      query. The proposed techniques have shown their performances and their robustness
      and are generalizable to all types of image databases.

PMID- 17543213
TI  - The story of the discovery of aquaporins: convergent evolution of ideas--but who
      got there first?
AB  - A critical analysis of the discovery of the first water channel protein (later
      called aquaporin 1) has been performed. In 1986 Benga's group in Cluj-Napoca,
      Romania, published in Biochemistry, a US-based journal, the results of
      experiments that provided the first visual and tangible evidence that the very
      rapid water exchange that occurs through the membranes of the human red blood
      cell (RBC) is mediated by a particular protein or small group of proteins. Benga
      and co-workers did first see bands in a gel that corresponded to water
      transporters, and were the first to do so. In 1988 Peter Agre and co-workers in
      Baltimore, USA, while working on the rhesus blood group antigens, purified a
      "new" membrane protein that they called CHIP 28 (channel integral membrane
      protein of molecular weight 28 k). At the time they had no idea what its function
      was. In 1992 came the definitive experiment, that was done, according to Peter
      Agre in his Nobel Lecture, after much discussion with colleagues about the likely
      candidate function of their 'orphan' protein. In a paper published in 1992 in
      Science Agre and his group found that CHIP28 has the properties of a water
      channel protein. In 1993 the name of the protein was changed from CHIP28 to
      aquaporin 1. It became obvious that one of the labelled peaks observed by Benga's
      group (the one in the region of molecular weight ~35,000 to ~60,000) corresponds
      to glycosylated CHIP28 (aquaporin 1). So Benga and co-workers did first see bands
      in a gel that corresponded to water transporters, and were the first to do so.
      The "mercury labelling" experiments were confirmed and extended in Cluj-Napoca by
      Benga's group and the results were published in 1986 in European Journal of Cell
      Biology, another international journal. The work was reviewed by Benga in
      subsequent years in international series and even as a chapter in a book on water
      transport edited for a wellknown US-based publisher. Agre's group did include a
      reference to Benga's work in their Science paper; but this reference was only to
      a 1983 paper on protease resistance of "water channels" (which was relevant) and
      not the pertinent 1986 Biochemistry paper, or even the subsequent publications.
      The report of the recent exciting finding of possible involvement of aquaporins
      in epilepsy, published in 2005 in Proc Natl Acd Sci USA by a group including Agre
      failed to cite Benga and Morariu's novel and startling report in Nature in 1977.

PMID- 17543214
TI  - Who discovered the water channels (aquaporins)?

PMID- 17543215
TI  - A regrettable mistake in the award of the 2003 Nobel Prize in Chemistry: the
      omission of Gheorghe Benga, the first discoverer of the water channel protein in
      the red blood cell membrane.

PMID- 17543216
TI  - Water channel proteins: from their discovery in 1985 in Cluj-Napoca, Romania, to
      the 2003 Nobel Prize in Chemistry.
AB  - Water channel proteins, later called aquaporins, are transmembrane proteins that
      have as their main(specific) function the water transport across biological
      membranes. The first water channel protein (WCP), now called aquaporin 1, was
      identified or "seen" in situ (hence discovered) in the human red blood cell (RBC)
      membrane in 1985 by Benga's group (Cluj-Napoca, Romania). This was achieved by a
      very selective radiolabeling of RBC membrane proteins with the water transport
      inhibitor [203Hg]-p-chloromercuribenzene sulfonate (PCMBS), under conditions of
      specific inhibition. The presence and location of the WCP was discovered among
      the polypeptides migrating in the region of 35-60 kDa on the electrophoretogram
      of RBC membrane proteins. The work was first published in 1986 in Biochemistry
      and Eur. J. Cell Biol. and reviewed by Benga in several articles in 1988-2004. We
      have thus a world priority in the discovery of the first water channel in the RBC
      membrane, that was re-discovered by chance by the group of Agre (Baltimore, USA)
      in 1988, when they isolated a new protein from the RBC membrane, nick-named
      CHIP28 (channel-forming integral membrane protein of 28 kDa). However, in
      addition to the 28 kDa component, this protein had a 35-60 kDa glycosylated
      component, the one detected by Benga's group. Only in 1992 the Agre's group
      suggested that "it is likely that CHIP28 is a functional unit of membrane water
      channels". In 1993 CHIP28 was renamed aquaporin 1. Looking in retrospect, asking
      the crucial question, when was the first WCP, discovered, a fair and clear cut
      answer would be: the first WCP, now called aquaporin 1, was identified or "seen"
      (hence discovered) in situ in the human RBC membrane by Benga and coworkers in
      1985. It was again "seen" when it was purified in 1988 and again identified when
      its water transport property was found byAgre's group in 1992. If we make a
      comparison with the discovery of New World of America, the first man who has
      "seen" a part, very small indeed, of The New Land was Columbus; later, others,
      including Amerigo Vespucci (from whom the name derived), have better "seen" and
      in the subsequent years many explorers discovered the complexity of the Americas.
      Consequently, the initial discovery of the first water channel by Benga's group
      must be properly credited; the omission of Gheorghe Benga from the 2003 Nobel
      Prize in Chemistry (half of which was awarded to Peter Agre "for the discovery of
      the water channels") was a new mistake in the award of Nobel Prizes. Benga's
      claim is presented on the web site of the Ad Astra Association (www.ad
      astra.ro/benga). As can be seen on this site his recognition as a discoverer of
      the first water channel protein from the human RBC membrane is growing. Thousands
      of science-related professionals from hundreds of academic and research units, as
      well as participants in several international scientific events, have signed as
      supporters of Benga; his priority is also mentioned in several comments on the
      2003 Nobel Prize as presented on the site.

PMID- 17543217
TI  - Aquaporin superfamily with unusual npa boxes: S-aquaporins (superfamily, sip-like
      and subcellular-aquaporins).
AB  - Thirteen aquaporins have been identified in mammals. They all have highly
      conserved two asparagineproline-alanine (NPA) boxes that are important for the
      formation of water permeating pore except AQP11 and 12,which have low homology
      (~20%) with other AQPs and have poorly conserved NPA boxes. Such poorly conserved
      aquaporin-like sequences are widely found in database. Among them, SIPs from
      plants indeed have a water channel function and are localized in the cytosol,
      suggesting their roles in intracellular homeostasis. Based on their water channel
      function, at least in SIPs, and low homology with other AQPs, they will be
      subgrouped as a superfamily of AQPs. Accordingly, they are tentatively named S
      aquaporins (superfamily, SIP-like and subcellular-aquaporins). Currently, their
      functional and biological grounds for an independent subfamily are not sufficient
      and may be reclassified into several subgroups in the future. The disruption of
      one of S-aquaporins, AQP11, produced neonatally fatal polycystic kidneys. AQP11
      is also localized intracellularly. Further works on S-aquaporins will provide new
      insights into the functions and roles of aquaporins.

PMID- 17543218
TI  - Aquaporins and fluid transport: an evolving relationship.
AB  - How epithelia transport fluid is controversial and remains undetermined. Two
      routes are possible: (1) via cell membranes and their aquaporins, or (2)
      paracellular. Our laboratory has recently developed experimental evidence and
      theoretical insights for fluid transport across corneal endothelium, a leaky
      epithelium. Aquaporin 1 (AQP1) is the only AQP present in these cells, and its
      deletion in AQP1 null mice significantly affects cell osmotic permeability but
      not fluid transport, which militates against sizable water movements across the
      cell. In contrast,AQP1 null mice cells have reduced regulatory volume decrease
      (only 60% of control), which suggests an AQP1 role in either the function or the
      expression of volume-sensitive membrane channels/transporters. Fluid movements
      can be produced by electrical currents, and the direction of the movement can be
      reversed by current reversal or by changing junctional electrical charges with
      polylysine. A mathematical model of corneal endothelium predicts experimental
      observations only when based on paracellular electro-osmosis. Our novel paradigm
      for this preparation includes: (1) paracellular fluid flow; (2) a crucial role
      for the junctions as a site for electro-osmosis; (3) hypotonicity of the primary
      secretion; (4) an AQP role in regulation and not as a significant water pathway.

PMID- 17543219
TI  - Aquaporin-2 (AQP2): its intracellular compartment and trafficking.
AB  - Aquaporins (AQPs) are membrane proteins serving in the transfer of water and
      small solutes across cellular membranes. At least 7 isoforms, namely AQP1, AQP2,
      AQP3, AQP4, AQP6, AQP7 and AQP11 are expressed in the kidney. Among them, AQP2
      plays a pivotal role in the concentration of urine. AQP2 is expressed in the
      principal cells of the collecting ducts. It is localized in the intracellular
      compartment and is translocated to the cell surface upon anti-diuretic hormone
      stimulation. Analyses in cultured cells expressing AQP2 have provided clues to
      the trafficking of AQP2. AQP2 resides in the subapical vesicles, some of which
      are Rab11-positive, suggesting their close relationship with apical recycling
      endosomes. Upon stimulation with forskolin, AQP2 is translocated to the cell
      surface. After washout, AQP2 is endocytosed to early endosomes and then
      transferred to the apical storage compartment. Some of AQP2 is excreted as
      exosomes. Actin cytoskeleton plays important roles in the trafficking of AQP2.
      Analyses of molecules found in AQP2-containing vesicles will shed light on the
      mechanism of AQP2 translocation.

PMID- 17543220
TI  - Impact of glycerol gateway molecule in adipocytes.
AB  - Glycerol is one of the essential nutrients in the mammalian body. Glycerol
      released from adipocytes is delivered to the liver and used for gluconeogenesis.
      The molecular mechanism of glycerol transport across the cell membrane remains
      unclear. AQPadipose, which we identified in human adipose cDNA project and later
      found to be human AQP7, is expressed in adipose tissue, and upregulated during
      fasting. AQP7 belongs to the aquaglyceroporin subfamily to permealize glycerol as
      well as water. Loss of function mutation of AQP7 in human caused disturbance of
      normal rise of plasma glycerol. Disruption of AQP7 gene in mice resulted in
      profound hypoglycemia during prolonged fasting because of impaired glycerol
      supply to the liver. In obesity, AQP7 is overexpressed in visceral
      fat,accompanied by portal hyperglycerolemia and systemic hyperglycemia.
      Considered together, these works indicate that AQP7 functions as a glycerol
      gateway molecule in adipocytes.

PMID- 17543221
TI  - Priorities in the discovery of the implications of water channels in epilepsy and
      duchenne muscular dystrophy.
AB  - In addition to the priority in the discovery of the first water channel protein
      in the red blood cell membrane the group of Gheorghe Benga in Cluj-Napoca,
      Romania, also has a world priority in the discovery of the implications of water
      channel proteins in epilepsy and Duchenne muscular dystrophy. This priority is
      briefly presented here. In 1977 Benga and Morariu reported a decreased water
      permeability of red blood cells in children with idiopathic epilepsy (cases
      selected by Ileana Benga). This investigation was performed as part of a program
      of research of hydroelectrolytic alterations in child epilepsy. On the other hand
      the group of Gheorghe Benga has reported a decreased water permeability of RBC in
      patients with Duchenne muscular dystrophy. These findings were interpreted as an
      expression of generalized membrane defects affecting water permeability in
      epilepsy and Duchenne muscular dystrophy. In recent years this idea was confirmed
      by reports indicating aquaporin abnormalities in the brain of epileptic patients
      and in the muscle of Duchenne muscular dystrophy patients.

PMID- 17543222
TI  - In vivo silencing of aquaporin-1 by RNA interference inhibits angiogenesis in the
      chick embryo chorioallantoic membrane assay.
AB  - Aquaporin-1 (AQP1) is a water channel protein mainly expressed in endothelial and
      epithelial cells of many tissues, including the vasculature where it serves to
      increase cell membrane water permeability. Previous studies in active multiple
      myeloma patients and in AQP1 KO mice indicated an involvement of AQP1 in
      physiological and tumor angiogenesis. To understand the physiological role of
      AQP1 in angiogenesis, we used a 21-nucleotide small interfering RNA duplexes
      (siRNA) to knockdown AQP1 in the chick embryo chorioallantoic membrane (CAM), a
      commonly used in vivo assay to study both angiogenic and angiostatic molecules.
      Chicken AQP1 sequence was identified and utilized to synthesize a siRNA directed
      to the AQP1 sequence. We then tested the efficiency of the siRNA in vitro, using
      an AQP1 transfected cell line. The level of AQP1 protein reduction obtained using
      siRNA was 98 % and 92 % after 1 and 2 day transfection respectively. RNA
      interference experiments were then performed in vivo by using the CAM assay.
      Results showed that after 4 days of treatment, AQP1 siRNA was able to strongly
      inhibit angiogenesis. This is the first study showing the in vivo use of RNA
      interference technique in the CAM assay. Our results strongly support the
      hypothesis that AQP1 could have a key role in physiological and pathological
      angiogenesis.

PMID- 17543223
TI  - The surface energy of water: functional implications of hexagonal/cuboidal
      transformations in the surface arrays.
AB  - Hyde's scientific book The Language of Shape has emphasized the importance of
      minimum surfaces in the structure of biological membranes. Minimum surfaces can
      be visualized as the property which brings many droplets of liquids to spherical
      bubbles, since a sphere has the minimum surface to volume ratio. Thus, a sphere
      with a surface of 4pir2 and volume of 4/3pir3 has a surface to volume ratio of
      3/r, that is, the ratio is dependent upon the reciprocal of the radius. The
      chemistry of water as dihydrides of the electronegative element oxygen is
      fundamentally dependent upon its polar properties and particularly the delta
      positive charges on the hydrogen atoms and the double delta negative charge on
      the larger oxygen atom, which from its mass (16 Da) is regarded as the centre of
      the water molecules. The cohesion of water as a liquid or as semi-crystal like
      structures in the surface depends upon electrostatic forces that are comparable
      in strength to covalent bonds. This review discusses the functional implications
      of some unexpected properties which have been evinced by model building and
      illustrated as a Poster in the 4th World Congress of Cellular and Molecular
      Biology.

PMID- 17543224
TI  - Delayed 24 hours Nomega-nitro-L-arginine methyl ester injection induces
      pharmacological cardioprotection against reperfusion injury.
AB  - Previous studies indicate that adenosine supplementation or nitric oxide synthase
      (NOS) inhibition during reperfusion exert protective effects against myocardial
      ischemia-reperfusion (I/R) injury. We wanted to test the hypothesis that NOS
      inhibition before I/R also protects the myocardium against further injury and
      aimed to determine the involvement of adenosine receptors in a perfused rat heart
      model. Rats were injected with 10 mg/kg of L-NAME (N(omega)-nitro-L-arginine
      methyl ester) or L-NAME + SPT (8-(p-sulfophenyl)-theophylline)--an adenosine
      antagonist - at 2 x 25 mg/kg or with a saline buffer, 24 hrs prior to heart
      excision. The hearts, perfused retrogradely were subjected to 60 min of global
      ischemia followed by 120 min reperfusion. L-NAME decreased NOx (nitrite and
      nitrate) production (16.2 +/- 3.2 vs. 7.0 +/- 1.8 micromol/L; P<0.05) in vivo and
      increased the release of troponin I (0.04 +/- 0.01 vs. 0.02 +/- 0.01 microg/L;
      P<0.05) in the plasma, compared to controls. After 120 min of reperfusion, there
      was a higher release of adenosine (26.1 +/- 2.2 vs. 2.4 +/- 1.2 nmol/min; P<0.01)
      and a decrease in troponin I levels (0.19 +/-0.07 vs. 0.59 +/- 0.16 ng/min;
      P<0.05) in the L-NAME group compared to controls. These results were accompanied
      by a higher proportion of recovery of left ventricular developed pressure (72.0
      +/- 4.0 vs. 60.0 +/- 4.0%; P<0.05) and coronary flow (72.0 +/- 5.0 vs. 51.0 +/-
      4.0%; P<0.05) in the L-NAME group. These beneficial effects were not blocked by
      the adenosine receptor antagonist. The present study reveals that L-NAME protects
      against I/R injury when the inhibitor is administered 24 hrs before ischemia. The
      beneficial effects observed in this model appear to be independent of adenosine
      receptor stimulation.

PMID- 17543225
TI  - Adenosine metabolism and its effect on methylation potential in cultured cells:
      methodological considerations.
AB  - Cell culture models are frequently used to study the role of adenosine in several
      physiological and pathological processes. In the present study, we have shown
      that adenosine deaminase activity in medium supplemented with calf serum
      significantly reduces adenosine concentration in culture medium. In the presence
      of HepG2 cells, the adenosine concentration in culture medium is decreased much
      faster, because a large amount of exogenous adenosine is metabolized by cellular
      enzyme. In order to measure intracellular adenosine, inosine, adenine
      nucleotides, S-adenosylhomocysteine (AdoHcy) and Sadenosylmethionine (AdoMet)
      contents, two methods for cell harvesting were compared. First, cells were
      removed with trypsin/EDTA, second, cells were lysed in cell culture dishes
      immediately after removing culture medium. Our results show that exact
      determination of adenosine metabolites requires immediate inactivation of
      metabolism by cell lysis in culture dishes. Application of adenosine (1mM)
      resulted in a time-dependent increase in intracellular adenosine, inosine, AMP,
      ATP, AdoHcy and AdoMet concentration. Since AdoHcy levels increased to a larger
      extent than AdoMet, the methylation potential, expressed as the ratio of
      AdoMet/AdoHcy, was reduced from 51.8 (control) to 2.9 (adenosine 1 mM, 2 hrs),
      suggesting that AdoMet-dependent methylation reactions might be impaired. In
      conclusion our data demonstrate that extracellular adenosine concentration and
      intracellular metabolite concentration strongly depend on the methods used to
      culture and harvest the cells.

PMID- 17543227
TI  - Mitochondrial changes induced by natural and synthetic asbestos fibers: studies
      on isolated mitochondria.
AB  - Asbestos fibers, such as chrysotile and crocidolite, are known to have cytotoxic
      effects on different cell types. In vivo exposure to asbestos fibers can induce
      both fibrotic and malignant lung diseases , however, the mechanisms linking
      exposure to the subsequent development of the diseases are unknown. Numerous
      investigations suggest the involvement of reactive oxygen species (ROS). ROS are
      known to damage biological macromolecules including proteins, cell membrane
      lipids and nucleic acids; alterations of these essential cellular components can
      alter cell function and can drive the cell to neoplastic transformation or to
      cell death. Because the mitochondrial respiratory chain is an important source of
      ROS and RNS (reactive nitogen species) in the cells, we have investigated the
      effects of aqueous extracts of asbestos (natural and synthetic) fibers on some
      mitochondrial activities. Our data show that crocidolite fibers release
      substances in solution that may interfere directly with the mitochondrial
      cytochrome oxidase complex. Moreover, the calcium ions released from these fibers
      induce opening of the permeability transition pore of the inner membrane leading
      to a possible cytotoxic effect due to the release of apoptotic factors normally
      localized in the mitochondrial intermembrane space. In addition, crocidolite
      extracts enhance the mitochondrial production of ROS. No significant biochemical
      effects are exerted by chrysotile, either natural or synthetic, on isolated
      mitochondria. Nevertheless, all asbestos fibers tested induce morphological
      alterations visualized by transmission electron microscopy and morphometric
      analysis.

PMID- 17543230
TI  - Pesticides and metals induced Parkinson's disease: involvement of free radicals
      and oxidative stress.
AB  - Environmental factors play a critical role in the etiology of Parkinson's disease
      in genetically susceptible aged individuals. Epidemiological findings have
      suggested the role of pesticides and metals in the onset and progression of
      Parkinson's disease. Environmental chemicals such as pesticides and metals
      induced PD animal models are established and evidences obtained from biochemical;
      molecular and behavioral studies indicated significant contribution of oxidative
      stress in PD. In this article, an update on the role of free radicals and
      antioxidants in the onset and progression of pesticides and metals induced PD has
      been discussed.

PMID- 17543231
TI  - Protective efficacy of semi purified fraction of high altitude podophyllum
      hexandrum rhizomes in lethally irradiated Swiss albino mice.
AB  - A fraction of high altitude Podophyllum hexandrum rhizome, REC-2006, was
      evaluated for its radioprotective efficacy against lethal gamma-irradiation (10
      Gy, whole body) in Swiss albino mice. The maximum tolerated dose (MTD) and LD50
      of this fraction were found to be 45 mg/kg b.w. and 74 mg/kg b.w. respectively.
      Pre-irradiation (- 2 h, ) administration (i.p.) of 6 or 8 mg/kg b.w. of REC-2006
      rendered > 90% survival in lethally irradiated mice. The dose reduction factor
      was calculated to be 1.62 considering survival as the end point. REC-2006
      treatment marked in significant increase in endogenous spleen colony forming
      units. In REC-2006 treated group, super oxide dismutase activity was increased
      significantly compared to the radiation control group (Liver, p = 0.00, Jejunum p
      = 0.00). The extract also inhibited radiation induced lipid peroxidation in liver
      (p = 0.00) at 24 h. REC-2006 administration (100-200 microg/ml) significantly
      reduced the halo diameter in mice thymocytes. Nearly 10 fold difference between
      the effective dose (6 mg/kg b.w.) and LD50 and the high degree of whole body
      survival (> 90% against 10 Gy irradiation) indicates REC-2006 to be safe and
      highly promising to achieve significant radioprotection against lethal radiation.
      Further purification and identification of active molecules and their efficacy
      studies in higher animals therefore demand attention.

PMID- 17543232
TI  - Free radicals and theophylline neurotoxicity : an experimental study.
AB  - Free radicals play a crucial role in health and disease and both reactive oxygen
      species (ROS) and reactive nitrogen species (RNS) have been implicated in CNS
      effects like excitotoxicity. Theophylline, a re-emerging drug for the treatment
      of obstructive airway disease, has a narrow therapeutic index which precludes its
      safe use. The present study evaluated the possible involvement of free radicals
      in theophylline induced seizures in mice. Aminophylline (100-250 mg/kg)
      consistently induced seizures and post-ictal mortality, and conventional
      anticonvulsants and adenosine agonists were ineffective in antagonizing them.
      Further, phosphodiesterase inhibitors, per se, also did not show any significant
      seizurogenic potential. Pretreatments with antioxidants, ascorbic acid, alpha
      tocopherol and melatonin, all dose dependently reduced seizure incidence and
      mortality after aminophylline, whereas, antioxidant depletion potentiated such
      excitotoxicity. Pretreatments with the NO synthase inhibitors, L-NAME and 7-NI
      blocked aminophylline seizures, whereas, the NO mimetics, L-arginine and glyceryl
      trinitrate, tended to potentiate this phenomenon. Sub-effective doses of
      aminophylline (100 mg/kg) also induced seizures when combined with subthreshold
      intensity of electroshock, and such seizures were similarly antagonized by the
      antioxidants and NO synthase inhibitors. Biochemical assay of brain homogenates
      showed that aminophylline seizures were associated with enhancements in brain MDA
      and NOx (NO metabolites) levels, whereas, SOD activity was reduced, and these
      changes were attenuated after melatonin and L-NAME pretreatments. The
      pharmacological and biochemical data are strongly suggestive of the involvement
      of both ROS and RNS during theophylline-induced seizures.

PMID- 17543233
TI  - The other side of the coin: beneficiary effect of 'oxidative burst' upsurge with
      T11TS facilitates the elimination of glioma cells.
AB  - Free radicals and allied molecules are the potential threats for the cellular
      components when they are produced in excess amount and cause different
      pathophysiological disorders including aging. Contrary to their detrimental
      effects, these molecules, in the other hand, can be utilized by the Phagocytic
      cells to destroy the abnormal cells and cellular components. Generation of
      reactive oxygen species (ROS) and nitric oxide (NO) are used as important
      effector molecules by Phagocytic macrophage/microglia to eliminate neoplastic
      cells in glioma bearing rat model. The glycoprotein T11TS/SLFA-3, by binding with
      CD2 receptor of macrophage/microglia, induces the generation of these reactive
      species when applied in three consecutive doses in glioma bearing animals. The
      CR3 family receptor CD11b is also correlated with the Phagocytic activity of the
      cells. The 'controlled' and directed production of ROS and NO by phagocytes
      induce cell death signals to the glioma cells and resulted in phagocytic
      destruction and apoptosis. The death signals generated by the free radicals and
      associated molecules resulted in accumulation of p53 proteins in the glioma
      cells. This oxidative stress induced p53 protein accumulation in neoplastic cells
      direct them to die by apoptosis. Therefore, the same oxidative stress causing
      pathophysiological problems, are used here to destroy the glioma cells by the
      macrophage/microglia in the delicate CNS tissue.

PMID- 17543234
TI  - Allium sativum constituents: effect on free radical generation from rat
      neutrophils.
AB  - Reactive oxygen species formation or respiratory burst by the neutrophils helps
      to remove the invaded pathogens and thus constitute a major defense against
      pathogenic microorganisms. Production of these radicals by activated neutrophils
      at the site of inflammation however inflicts damage to the host tissue.
      Modulation of the neutrophil respiratory burst is therefore important in
      determining the balance between immune defense and host tissue injury during
      inflammatory conditions. Garlic extracts and various compounds isolated from
      garlic have been found to possess various activities, however no report is
      available on their effect on neutrophil free radical generation. The present
      study was therefore undertaken to evaluate the effect of garlic aqueous extract,
      alcoholic extract and various fractions on the free radical generation from
      neutrophils. Among the tested fractions, chloroform fraction of garlic seems to
      be very potent in attenuating the free radical generation from rat neutrophils,
      which could be beneficial in the inflammation associated pathological conditions.

PMID- 17543235
TI  - Hyperglycemia induced oxidative stress in type-1 and type-2 diabetic patients
      with and without nephropathy.
AB  - Diabetes mellitus is associated with hyperglycemia, hyperlipoproteinaemia and
      oxidative stress at cellular level. The aim of the present study was to determine
      the relationship between anti-oxidative system of cells and hyperglycemia induced
      reactive oxygen species (ROS) in type-1 and type-2 diabetic patients with and
      without nephropathy. ROS are anihilated by an intracellular enzymatic system such
      as glutathione peroxidase (GPx) and catalase and the reduced glutathione (GSH) is
      the major antioxidant of erythrocytes and plasma. Total of 200 diabetic patients
      and 50 of normal healthy control individuals were recruited for the present
      study. Erythrocytes and plasma activities of GPx, catalase and GSH were measured
      as a part of anti-oxidative system and TBARS for the marker of oxidative stress
      in type-1 diabetes mellitus (T1DM), type-2 diabetic mellitus (T2DM), type-1
      diabetes with nephropathy (T1DN) and type-2 diabetes with nephropathy (T2DN)
      patients. GPx, catalase and GSH activity was significantly decreased, whereas
      TBARS level was significantly increased in both type-1 and type-2 diabetic groups
      with and without nephropathy than the normal healthy individuals. T1DM patients
      had shown decreased level of GSH and activity of anti-oxidative enzymes than T2
      DM patients, whereas TBARS level was higher in T1DM than T2DM patients,
      suggesting that T1DM patients are more prone to secondary complications such as
      nephropathy than T2DM patients. Obtained results have shown positive correlation
      of GSH with GPx and catalase activity in erythrocytes and plasma, whereas,
      negative correlation was observed between TBARS and catalase in erythrocytes and
      plasma indicative of the relationship of various anti-oxidative enzymes and key
      antioxidant such as GSH in erythrocytes and plasma responsible for increased
      oxidative stress.

PMID- 17543236
TI  - Evaluation of liver function impairment and lipid peroxidation induced by lantana
      camara leaf powder administration in adult rat serum and liver.
AB  - Lantana camara is a common weed and certain medicinal properties have been
      attributed to this plant, but most varieties of this plant are reported to be
      highly toxic to animals. The plant is a native of America but a few varieties are
      indigenous to tropical Asia and Africa. The present investigation was done to
      study the hepatotoxic and lipid peroxidative effects of this noxious weed on
      female Wistar rats. Eighty four percent (84%) increase was observed in the
      activity of AST in group B and 120% increase was noted in group C in serum. In,
      liver tissue this increase was 66% and 258%. In the case of ALT, 165% increase
      was observed in group B and 219% increase was observed in group C in serum. In,
      liver there was 46% increase in group B and 216% increase in group C in the ALT
      activity. Similarly, 30% and 50% increase in group B and 120% and 300% increase
      in group C in the activity of ALP was observed with respect to control group. The
      overall protein concentration was increased in serum and decreased in liver
      tissue. Lipid peroxidation in liver tissue was inhibited by 22% in group B and
      55% in group C. Thus Lantana camara is a toxic plant which produces severe
      hepatotoxicity in rats, but it also prevented lipid peroxidation that may suggest
      that Lantana camara may be acting as antioxidant but, exactly which of its
      component is responsible for this activity is not known and needs future
      investigations.

PMID- 17543237
TI  - Molecular mechanisms underlying wound healing and anti-inflammatory properties of
      naturally occurring biotechnologically produced phenylpropanoid glycosides.
AB  - Two phenylpropanoid glycosides, verbascoside (VB) and teupolioside (TP), produced
      biotechnologically by Syringa vulgaris and Ajuga reptans plant cell cultures,
      were studied in vitro and in vivo for their anti-inflammatory and wound healing
      activities. It was shown that TP- and VB-containing extracts significantly
      accelerated wound healing and possessed remarkable anti-inflammatory action in
      the excision wound model. These effects correlated with the inhibition of
      reactive oxygen species release from the whole blood leukocytes and with the
      ferrous ion chelating capacity. On the other hand, they don't correlate either
      with free radical scavenging or with the inhibition of lipid peroxidation in the
      cell-free systems. Furthermore, both VB- and TP-containing extracts were
      extremely effective inhibitors of chemokine and growth factor expression by
      cultured human keratinocytes treated with pro-inflammatory cytokines, TNF-alpha
      and interferon-gamma.

PMID- 17543238
TI  - Dose dependent effect of ricin on DNA damage and antioxidant enzymes in mice.
AB  - Ricin a glycoprotein from the Ricinus communis seeds, is known to have diverse
      toxic effects on cells of different visceral organs. We have studied the effect
      of ricin (0.5, 1.0 and 2.0 LD50) on various oxidative stress markers at 1, 3 and
      7 day post exposure following i.p. administration in Swiss albino male mice.
      Results of this study revealed that ricin induces generation of reactive species,
      lipidperoxidation, DNA fragmentation and depletion of GSH. Activity of
      antioxidant cascade related enzyme like superoxide dismutase (SOD), glutathione
      peroxidase (GPx) decreased, while glutathione reductase (GR) and catalase
      activity increased. Superoxide dismutase and glutathione peroxidase activity was
      decreased significantly in liver, spleen and kidney. The decrease was more
      prominent on 7 day of post exposure in all the exposed doses. A significant
      increase in the activities of catalase was observed in plasma, liver, spleen and
      kidney on 7 day following ricin exposure. Glutathione reductase increased
      significantly as early as 24 h following 1.0 LD50 dose. Lipid peroxidation
      increased and non protein sulfhydryl content decreased in all the tissues at
      different time intervals. Total antioxidant status was reduced as early as 1 day
      post exposure. Nearly two fold increase was observed in DNA fragmentation
      following 0.5 LD50 dose of ricin on 1 day post exposure. DNA diffusion assay also
      indicated an early damage to DNA due to ROS. An early change in DNA
      fragmentation, DNA diffusion, and total antioxidant status and in the activity of
      various enzymes indicates that ricin produce oxidative stress by generation of
      reactive oxygen species as early as 24 h at a minimum dose of 0.5 LD50. Probably
      this is the first study which indicate that ricin induced oxidative stress at a
      minimum dose of 0.5 LD50.

PMID- 17543239
TI  - Cytoarchitectonic organization and morphology of the cells of hippocampal complex
      in strawberry finch, Estrilda amandava.
AB  - Neurons in the hippocampal complex (dorsomedial forebrain) were described and
      located following Golgi impregnation. Five fields were recognized in the
      hippocampal complex: medial and lateral hippocampus, parahippocampal area,
      central field of the parahippocampal area and crescent field. In the medial
      hippocampus three layers have been observed: suprapyramidal towards the pial
      surface, pyramidal at the central and infrapyramidal adjacent to the ventricle.
      Neurons of the hippocampal complex were classified in to two main cell groups:
      predominant projection neurons with spinous dendrites and local circuit neurons.
      Projection neurons were further sub classified into three main types: pyramidal,
      pyramidal like, and multipolar neurons. In addition to these neurons, monotufted
      and bitufted neurons were also observed in the medial and lateral hippocampus
      with low frequency. The pyramidal neurons were dominant neuronal types in the
      pyramidal layer-II of the medial hippocampus, mixed with pyramidal like and
      multipolar neurons. Pyramidal and pyramidal-like neurons were found restricted in
      the pyramidal layer II of the medial hippocampus while the multipolar neurons
      were uniformly distributed in all subfields of the hippocampal complex. In the
      lateral hippocampus irregular shaped radial glial cells were present near the
      ventricular wall and projecting their dendrites towards the pia. Second group of
      local circuit neurons with local arborization of their projections were present
      in the medial hippocampus and in parahippocampal area.

PMID- 17543240
TI  - The aging spine: the role of inflammatory mediators in intervertebral disc
      degeneration.
AB  - Human intervertebral disc undergoes multifactorial biochemical and morphologic
      degenerative changes during the process of aging. The frequency of degeneration,
      especially lumbar degeneration increases sharply with age and is regarded as a
      major cause of discogenic low back pain. Since degenerative discs are often
      asymptomatic, the pathobiology of discogenic back pain remains unclear.
      Degenerated discs spontaneously produce increased amounts of inflammatory
      mediators suggesting their role in the degenerative process of the intervertebral
      disc. However, the relationship between aging, degenerative processes, and actual
      illness is far from clear. Basic science research has demonstrated that the
      intervertebral disc is an avascular tissue element occupied by inadequately
      characterized cells in an extensive extracellular matrix. While the annulus
      fibrosus is predominantly collagenous, the matrix of the central nucleus pulposus
      is rich in proteoglycans. With aging, the substance of proteoglycans
      significantly decreases which is believed to be a critical factor in
      intervertebral disc degeneration. A variety of inflammatory mediators have been
      implicated in the degeneration of the intervertebral disc including nitric oxide
      (NO), interleukins, matrix metalloproteinases (MMP), prostaglandin E2 (PGE2),
      tumor necrosis factor alpha (TNF-alpha) and a group of cytokines. MMPs, PGE2, and
      a variety of cytokines have been already been shown to play a role in the
      degradation of articular cartilage. Nitric oxide is a novel mediator that is
      drawn into much attention recently for its role in disc abnormalities. Elevated
      nitric oxide production derived from NO synthase activity has been manifested in
      cerebrospinal fluid in patients with degenerative lumbar disease. However, the
      regulatory mechanism of NO and its relationship to the clinical manifestations
      are unclear. The biochemical events that occur with the 'aging spine' and in
      particular, the role of inflammatory mediators in intervertebral disc
      degeneration have not been studied assertively. Correspondingly, the association
      between degeneration of the intervertebral disc and the nociceptive mechanism of
      back pain is also not fully elucidated. However, there is high incidence of
      degenerated disc disorders manifested as back and neck pain and are among the
      most commonly encountered complaints in elderly population. It is hypothesized
      that the degenerative cascade ultimately leads to extensive structural defects
      and loss of normal motion segment function and configuration.

PMID- 17543241
TI  - Echocardiography and cardiovascular magnetic resonance: evolution as
      complementary imaging tools.

PMID- 17543242
TI  - Who cares for the patient with heart failure?
AB  - Heart failure is a progressive and often fatal clinical syndrome caused by
      cardiac dysfunction. Therapeutic advances in both acute and chronic heart failure
      care have resulted in the ability to partially or completely reverse cardiac
      dysfunction, with accompanying reductions in attributable morbidity, mortality,
      and cost. In order to examine who is best suited to provide care for the patient
      with heart failure, we must recognize that treatment options vary in relationship
      to the stage of the disorder. Use of a contemporary heart failure classification
      scheme facilitates stratification of primary and secondary prevention and
      tertiary care options.

PMID- 17543243
TI  - Management of heart failure patients using telemedicine communication systems.
AB  - Heart failure (HF) continues to place significant demands on health care
      resources because of the large number of hospital admissions for HF, the growth
      of the elderly population with HF, and the improved survival of patients with
      chronic heart disease who develop HF that requires continuous care. Because HF is
      best managed using a disease management approach, frequent communication is an
      important component of care. A variety of studies using the telephone to maintain
      communication have demonstrated reduced hospital admissions and improved
      morbidity rate. Hardware monitoring systems that can record vital signs and
      transmit information from the home to a data center have also demonstrated their
      value in HF care, but such systems become expensive when considered for large
      populations of HF patients. Most HF patients can transmit their vital signs,
      weight, and symptoms to a practice data center using the Internet with no
      specialized hardware other than a sphygmomanometer and a scale. We have used such
      a system to monitor HF patients and have provided care instructions using the
      same system. With use of an Internet communication system, it is possible to
      reduce hospitalizations and maintain a stable HF status without frequent office
      visits.

PMID- 17543244
TI  - Impedance cardiography: more questions than answers.
AB  - Thoracic electrical bioimpedance, also known as impedance cardiography (ICG), is
      a noninvasive method to obtain hemodynamic measurements, including cardiac
      output. Recently, there has been a flurry of reports on the clinical use of ICG.
      Authors have suggested that ICG measurements are useful for a myriad of
      situations, including diagnosis of heart failure, monitoring of a patient's
      clinical status, and assisting in medicine titration decisions. However, data
      continue to suggest poor correlation between current generation ICG devices and
      invasive measurements of cardiac output, especially in heart failure patients.
      ICG is also not able to accurately measure left ventricular filling pressures.
      There are limited data demonstrating any improved outcomes using ICG in the
      clinical setting. Given the available data, ICG use should be limited to the
      research setting.

PMID- 17543245
TI  - Implantable hemodynamic monitoring devices in heart failure.
AB  - The syndrome of heart failure is characterized by symptoms that are relatively
      insensitive and nonspecific. Physical diagnosis may be unreliable even in the
      hands of experienced clinicians despite the presence of significantly elevated
      filling pressures or a significantly depressed cardiac output. Over the past
      decade, the implantable hemodynamic monitor (IHM) has been developed as means of
      measuring intracardiac pressures over time and understanding the nuances of the
      hemodynamic derangements of this condition. With improved ability to accurately
      assess and monitor filling pressures, clinicians can more precisely adjust
      therapy with the goal of improving patient symptoms and possibly outcomes. Future
      directions include using the IHM to assist in management of other cardiovascular
      diseases, such as pulmonary arterial hypertension, and combining this technology
      with other implanted devices, such as defibrillators.

PMID- 17543247
TI  - The ESCAPE trial.

PMID- 17543246
TI  - Who should pay for home monitoring of heart failure?
AB  - Despite the recent advancement in medical therapy for heart failure, morbidity
      associated with heart failure continues to be excessive, with rising
      hospitalization rates and costs. Disease management models have been instituted
      successfully for several chronic disease states, and observational trials have
      shown different models to be beneficial. A multidisciplinary approach to
      management of heart failure improves outcomes. Multiple recent trials involving
      various models of integrated and comprehensive disease management have
      demonstrated promising results, such as reduction in mortality and
      hospitalizations. Future models for disease monitoring may include implantable
      devices that directly monitor hemodynamics combined with multidisciplinary care.

PMID- 17543248
TI  - Management of the cardiorenal syndrome in heart failure.
AB  - Heart failure treatment has seen great improvements in the past few decades. In
      many cases of heart failure, coexisting renal dysfunction, known as the
      cardiorenal syndrome, complicates treatment. Renal dysfunction is known to be a
      predictor of increased mortality. Renal dysfunction can be caused by various
      hemodynamic forces, medications, and intrinsic renal disease. With an
      understanding of the underlying etiology and physiology of the renal dysfunction,
      the appropriate treatment strategy can be planned. This understanding can also
      indicate when it is necessary to resort to therapies such as left ventricular
      assist device or dialysis. Such targeting of therapy can improve the prognosis of
      patients with heart failure and renal dysfunction.

PMID- 17543249
TI  - The problem of polypharmacy in heart failure.
AB  - Improvements in the medical therapy for chronic heart failure have led to a
      dramatic decrease in the morbidity and mortality of patients with heart failure
      over the past two decades. This improvement has been gained at the expense of an
      increasing number of potent drugs that heart failure patients have to take
      chronically. Because heart failure forms the end-stage of different
      cardiovascular diseases and their predisposing risk factors, patients need drug
      treatment not only for heart failure itself but also for related conditions. Even
      more, because most heart failure patients are elderly, a number of unrelated,
      noncardiovascular diseases become apparent, which further increase the number of
      pharmaceutical substances with which heart failure patients are treated. The
      resulting polypharmacy leads to problems including economic burden, patient
      compliance, and most importantly, partly unpredictable drug interactions. This
      article reviews the existing data concerning some of these problems, to provide
      an aid for choosing the appropriate drugs in heart failure patients and
      minimizing the patient's risk.

PMID- 17543250
TI  - The frequency, impact, and management of mitral regurgitation in patients with
      heart failure.
AB  - Management of severe chronic mitral regurgitation (MR) in severe heart failure is
      challenging. There are controversies over the efficacy of surgical correction of
      MR in the presence of severely depressed left ventricular (LV) function. The
      etiology of MR plays an important role in clinical decision making. In organic
      MR, surgical correction should be performed even if patients have an LV ejection
      fraction of less than or equal to 30%. In functional MR, treatment of myocardial
      damage should be considered as the priority. The long-term mortality benefit of
      surgical correction of functional MR associated with severe LV dysfunction caused
      by cardiomyopathy (ischemic or dilated) likely depends on whether myocardial
      dysfunction can be reversed or improved by treatments (eg, coronary artery
      revascularization, pharmacologic treatment). Preoperative examination of viable
      myocardium (ischemic and hibernating myocardium) helps to identify a surgical
      candidate with ischemic MR associated with ischemic cardiomyopathy. The role of
      device treatment of MR in heart failure needs further investigation with outcome
      data.

PMID- 17543251
TI  - Ventriculovascular coupling in systolic and diastolic heart failure.
AB  - Pressure-volume analysis has provided critical insight into ventricular
      mechanics, and it has elucidated the underlying mechanisms of heart failure (HF).
      Renewed interest in ventriculovascular coupling, the interaction of the left
      ventricle and the arterial system, has developed from recent investigations
      focusing on the importance of heart rate control in systolic HF, blood pressure
      lability in the elderly, and acute pulmonary edema in patients with HF and a
      normal ejection fraction. These data suggest that abnormal ventriculovascular
      coupling may be an additional pathophysiologic mechanism underlying the
      development of HF with a normal ejection fraction and may provide a target for
      novel therapies.

PMID- 17543252
TI  - Peripheral opioid antagonists: a therapeutic advance for optimizing opioid
      gastrointestinal tolerability.

PMID- 17543253
TI  - Rx package inserts: redesigned with fewer errors in mind.

PMID- 17543254
TI  - Metformin and glitazones: do they really help PCOS patients?
AB  - BACKGROUND: Polycystic ovarian syndrome (PCOS) leads to a multitude of clinical
      and biochemical alterations in patients. Metformin and the thiazolidenediones
      (TZDs)--which have insulin-sensitizing properties--are believed to be effective
      in minimizing the changes caused by this syndrome. OBJECTIVES: Our goal was to
      assess the evidence for the use of TZDs or metformin in the treatment of PCOS
      patients. In addition, we sought to assess and compare the effectiveness of
      metformin vs TZDs in the clinical and biochemical regression of PCOS based on
      available randomized controlled trials (RCTs). SEARCH STRATEGY: We searched
      Medline (January 1966 to January 2007), PubMed (January 1954 to January 2007),
      Google Scholar search engine (through January 2007), and reference lists of
      articles. We also contacted researchers and clinicians in the field. SELECTION
      CRITERIA: We reviewed RCTs involving women diagnosed with PCOS (based on 1990 the
      National Institutes of Health Criteria) who were treated with either metformin or
      TZDs. Trials were limited to those that were testing only the effects of either
      of these agents as their primary endpoint. MAIN RESULTS: A total of 115 trials
      were obtained, of which only 33 trials met the inclusion criteria. Ultimately, 31
      trials involving total 1892 patients were included in the analysis (23 metformin,
      2 rosiglitazone, 1 pioglitazone, 5 troglitazone) with 2 unobtainable trials.
      There was insufficient data to compare metformin to the TZDs in any parameter
      because the literature often contained inadequate quantitative data, or there
      were too few published trials. As a result, we performed the meta-analysis for
      metformin only. Among the outcomes examined, the only statistically significant
      changes were minimal decreases with metformin in ovulation rates and luteinizing
      hormone to follicle stimulating hormone ratio (LH/FSH), and an increase in
      fasting insulin. There was no clinically significant change with metformin in
      ovulation rate, pregnancy rate, body mass index, waist-to-hip ratio, hirsutism (F
      G score), LH/FSH, fasting insulin, fasting blood glucose, total testosterone,
      free testosterone, androstenedione, and dehydroepiandrosterone sulfate. AUTHORS'
      CONCLUSIONS: There is a paucity of data from RCTs to compare the effectiveness of
      metformin vs TZDs as well as the effects of either agent in treating the clinical
      and biochemical features of PCOS. Further research involving RCTs with larger
      sample sizes is needed before any recommendation can be made on the usefulness of
      these agents in the treatment of PCOS.

PMID- 17543255
TI  - Hurricane Katrina evacuee develops a persistent rash.

PMID- 17543256
TI  - Screening: new guidance on what and what not to do.

PMID- 17543257
TI  - Can history and exam alone reliably predict pneumonia?
AB  - BACKGROUND: Prediction rules based on clinical information have been developed to
      support the diagnosis of pneumonia and help limit the use of expensive diagnostic
      tests. However, these prediction rules need to be validated in the primary care
      setting. METHODS: Adults who met our definition of lower respiratory tract
      infection (LRTI) were recruited for a prospective study on the causes of LRTI,
      between November 15, 1998 and June 1, 2001 in the Leiden region of The
      Netherlands. Clinical information was collected and chest radiography was
      performed. A literature search was also done to find prediction rules for
      pneumonia. RESULTS: 129 patients--26 with pneumonia and 103 without--were
      included, and 6 prediction rules were applied. Only the model with the addition
      of a test for C-reactive protein had a significant area under the curve of 0.69
      (95% confidence interval [CI], 0.58-0.80), with a positive predictive value of
      47% (95% CI, 23-71) and a negative predictive value of 84% (95% CI, 77-91). The
      pretest probabilities for the presence and absence of pneumonia were 20% and 80%,
      respectively. CONCLUSIONS: Models based only on clinical information do not
      reliably predict the presence of pneumonia. The addition of an elevated C
      reactive protein level seems of little value.

PMID- 17543258
TI  - Clinical inquiries. What hormonal contraception is most effective for obese
      women?

PMID- 17543259
TI  - Clinical inquiries. History, exam, and labs: is one enough to diagnose acute
      adult appendicitis?

PMID- 17543260
TI  - Clinical inquiries. What is the best approach to goiter for euthyroid patients?

PMID- 17543261
TI  - Clinical inquiries. Which lifestyle interventions effectively lower LDL
      cholesterol?

PMID- 17543262
TI  - Clinical inquiries. Which diuretics are safe and effective for patients with a
      sulfa allergy?

PMID- 17543263
TI  - Clinical inquiries. What's the best diagnostic evaluation of night sweats?

PMID- 17543264
TI  - Spatial modelling and risk factors of malaria incidence in northern Malawi.
AB  - Identifying areas of high risk is crucial for providing targeted antimalarial
      interventions. This study used ecological spatial regression models to profile
      spatial variation of malaria risk and analysed possible association of disease
      risk with environmental factors at sub-district level in northern Malawi. Using
      malaria incidence data collected between January 2002 and December 2003, we
      applied and compared Bayesian Poisson regression models assuming different
      spatial structures. For each model we adjusted for environmental covariates
      initially identified through bivariate non-spatial models. The model with both
      spatially structured and unstructured heterogeneity provided a better fit, guided
      by the model comparison criteria. Malaria incidence was associated with altitude,
      precipitation and soil water holding capacity. The risk increased with altitude
      (relative risk (RR): 1.092, 95% interval: 1.020, 1.169) and precipitation (RR:
      1.031, 95% interval: 0.950, 1.120). At medium level of SWHC relative to low
      level, the risk was reduced (RR: 0.521, 95% interval: 0.298, 0.912), while at
      high level of SWHC relative to low level the risk was raised (RR: 1.649, 95%
      interval: 1.041, 2.612). Compared to the commonly used standardised incidence
      ratios, the model-based approach provided homogenous and easy to interpret risk
      estimates. Generally, the smoothed map showed less spatial variation in risk,
      with slightly higher estimates of malaria risk (RR>1) in low-lying areas mostly
      situated along the lakeshore regions, in particular in Karonga and Nkhatabay
      districts, and low risk (RR<1) in high-lying areas along Nyika plateau and Vwaza
      highlands. The results suggest that the spatial variation in malaria risk in the
      region is a combination of various environmental factors, both observed and
      unobserved, and the map only highlights the overall effect of these factors. The
      results also identified areas of increased risk, where further epidemiological
      investigations can be carried out. This study, therefore, constitutes an
      important first step and future models analysed at a sub-district level could be
      pursued to delineate priority areas for focussing of finite resources.

PMID- 17543265
TI  - Epizootiological importance of Glossina morsitans submorsitans (Diptera:
      Glossinidae) (Newstead) in the Ghibe River Valley, Southwest Ethiopia.
AB  - The epizootiological importance of Glossina morsitans submorsitans in Ghibe River
      Valley was undertaken from October 2000 to September 2001. The flies were
      collected using baited monoconical traps. G. m. submorsitans occurred with a mean
      apparent density of 4.26+/-0.49 flies/trap/day and the apparent density was
      characterized by an increase during the wet season and a decrease during the dry
      season. Among 450 G. m. submorsitans, approximately 5% were found to be infected
      with trypanosome. Of these infected flies, 76% were female. Nanomonas, Duttonella
      and Trypanozoon were the three trypanosome subgenera detected and occurred in the
      proportions of 57.1%, 38.1% and 4.8%, respectively. Among 139 blood meals of G.
      m. submorsitans collected, 54.68% were identified to group or species levels.
      Accordingly, 36.84%, 25%, 11.84% and 10.53% accounted for cattle, kudu, suidae
      (warthog and/or wild pig) and human, respectively and others such as goats
      (6.58%), bovidae (5.26%), baboon (2.63%) and water buck (1.32%). While 21.05% of
      the blood meals were found to be out of detection range.

PMID- 17543266
TI  - Role of the counterions on the adsorption of ionic surfactants.
AB  - A theory accounting for the effect of the counterions on the adsorption constant,
      K, is proposed. The experimental values of K were determined by using surface and
      interfacial tension isotherms measured by us or available in the literature. By
      accounting for the adsorption energy u 0 of the counterion, a generalization of
      Gouy equation and a modified expression for the adsorption constant, K, are
      derived. The adsorption energy is calculated from the London equation, which
      involves the polarizabilities alpha 0i and the ionization potentials Ii of the
      respective components and the radius Rh of the hydrated ion. By careful analysis
      of the available experimental data for alpha 0i, Ii and Rh, coupled with some
      reasonable hypothesis, we succeeded to obtain linear dependences between the
      calculated values of u 0 and the experimental data for lnK with slopes rather
      close to the theoretical ones. The obtained results for u 0 were used to
      calculate the disjoining pressure isotherms of foam films stabilized by DTAF,
      DTACl and DTABr. It turned out that the type of the counterion has significant
      effect on the disjoining pressure.

PMID- 17543267
TI  - [The 2007 players in clinical research - or where we stand within the new law].

PMID- 17543268
TI  - [Salivary involvement in IgG4-related multifocal fibrosclerosing disease].
AB  - OBJECTIVES: To report a case of IgG4-related multifocal fibrosclerosis, revealed
      by a multifocal salivary involvement. MATERIAL AND METHODS: A 59-year-old man,
      with chronic pancreatitis, was managed for fibrotic involvement of the 2
      submaxillary glands and the 2 parotids. Clinical, radiological, and histologic
      features were retrospectively studied. RESULTS: Pathological features of
      submandibular gland revealed a chronic sclerosing sialadenitis. Retroperitoneal
      fibrosis in computed tomography and high rate of IgG4 are objectived. The
      diagnosis of IgG4-related multifocal fibrosclerosis is evoked. The patient's
      state improved with corticosteroid therapy. CONCLUSION: Salivary involvement in
      IgG4-related multifocal fibrosclerosis must be recognized in salivary medical
      pathology.

PMID- 17543269
TI  - Influence of cyanine dye structure on self-aggregation and interaction with
      nucleic acids: a kinetic approach to TO and BO binding.
AB  - Kinetics and equilibria of cyanine dyes thiazole orange (TO) and benzothiazole
      orange (BO) self-aggregation and binding to CT-DNA are investigated in aqueous
      solution at 25 degrees C and pH 7. Absorbance spectra and T-jump experiments
      reveal that BO forms J-aggregates while TO forms more stable H-aggregates.
      Fluorescence and absorbance titrations show that TO binds to DNA more tightly
      than BO. TO stacks externally to DNA for low polymer-to-dye concentration ratios
      (C(P)/C(D)) while dye intercalation occurs for high values of C(P)/C(D). T-jump
      and stopped-flow experiments performed at high C(P)/C(D) agree with reaction
      scheme D+S <=> D,S <=> DS(I) <=> DS(II) where the precursor complex D,S evolves
      to a partially intercalated complex DS(I) which converts to the more stable
      intercalate DS(II). Non-electrostatic forces play a major role in D,S
      stabilization. Last step is similar for both dyes suggesting accommodation of the
      common benzothiazole residue between base pairs. Experiments using poly(dA
      dT).poly(dA-dT) and poly(dG-dC).poly(dG-dC) confirm base pair preference for TO.

PMID- 17543270
TI  - Differences in the palatal rugae shape in two populations of India.
AB  - OBJECTIVES: The aim of the study was to investigate differences in the shape of
      the palatal rugae in two populations of India and develop discriminant function
      to identify the populations based on rugae shape. METHODS: Thirty plaster casts
      from each population group, equally distributed between the sexes and belonging
      to similar age-group, were examined for rugae shape (straight, wavy, curved,
      unification and circular) and their incidence recorded. Association between rugae
      shape and population as well as rugae shape and sex were tested using chi-square
      analysis and discriminant function developed using SPSS 10.0 statistical package.
      RESULTS: Wavy and curved were the most prevalent rugae shape in both groups,
      followed by straight rugae. Unifications were few in number while circular rugae
      were not observed. Chi-square analysis for association between rugae shape and
      population groups showed significant differences in straight and curved forms. No
      significant sex differences were observed. Three rugae shapes - straight, wavy
      and curved - contributed to the discriminant function which enabled population
      identification with an accuracy of 70%. CONCLUSIONS: Palatal rugae shape revealed
      significant differences between the two Indian populations and also confirmed
      previous reports of lack of sex dimorphism. Discriminant function analysis
      allowed moderate differentiation of the populations and it is inferred that
      discrete variables such as rugae shape are better suited for the purpose than
      continuous variables such as rugae length. However, these interpretations are
      precluded by the small sample size and further work on larger samples is required
      to validate the findings.

PMID- 17543271
TI  - Osteogenic phenotypes and mineralization of cultured human periosteal-derived
      cells.
AB  - Stem cells or osteogenic precursor cells isolated from bone marrow, trabecular
      tissues in bone, cartilage, muscle, and fat are the most suitable source for bone
      tissue engineering. In this study, we investigated the osteogenic phenotypes and
      mineralization of cultured human periosteal-derived cells obtained from
      mandibular periosteums. These periosteal-derived cells were positive for CD44,
      CD90, and CD166 antigens. They are successfully differentiated into osteoblasts
      in the medium containing dexamethasone, ascorbic acid, and beta-glycerophosphate.
      We observed that alkaline phosphatase (ALP) was largely expressed in the earlier
      stage of osteoblastic differentiation according to histochemical staining and RT
      PCR analysis, whereas osteocalcin was dominantly expressed and secreted into the
      medium at the later stage. In addition, mineralized nodule formation has been
      observed by von Kossa staining in a time-dependent manner. These results suggest
      that periosteal-derived cell has the potential osteogenic activity and could be a
      good candidate for tissue engineering to restore the bony defects of the
      maxillofacial region.

PMID- 17543272
TI  - Functional roles of arginine residues in mung bean vacuolar H+-pyrophosphatase.
AB  - Plant vacuolar H+-translocating inorganic pyrophosphatase (V-PPase EC 3.6.1.1)
      utilizes inorganic pyrophosphate (PPi) as an energy source to generate a H+
      gradient potential for the secondary transport of ions and metabolites across the
      vacuole membrane. In this study, functional roles of arginine residues in mung
      bean V-PPase were determined by site-directed mutagenesis. Alignment of amino
      acid sequence of K+-dependent V-PPases from several organisms showed that 11 of
      all 15 arginine residues were highly conserved. Arginine residues were
      individually substituted by alanine residues to produce R-->A-substituted V
      PPases, which were then heterologously expressed in yeast. The characteristics of
      mutant variants were subsequently scrutinized. As a result, most R-->A
      substituted V-PPases exhibited similar enzymatic activities to the wild-type with
      exception that R242A, R523A, and R609A mutants markedly lost their abilities of
      PPi hydrolysis and associated H+-translocation. Moreover, mutation on these three
      arginines altered the optimal pH and significantly reduced K+-stimulation for
      enzymatic activities, implying a conformational change or a modification in
      enzymatic reaction upon substitution. In particular, R242A performed striking
      resistance to specific arginine-modifiers, 2,3-butanedione and phenylglyoxal,
      revealing that Arg242 is most likely the primary target residue for these two
      reagents. The mutation at Arg242 also removed F- inhibition that is presumably
      derived from the interfering in the formation of substrate complex Mg2+-PPi. Our
      results suggest accordingly that active pocket of V-PPase probably contains the
      essential Arg242 which is embedded in a more hydrophobic environment.

PMID- 17543273
TI  - Examination of chlorophyll fluorescence decay kinetics in sulfur deprived algae
      Chlamydomonas reinhardtii.
AB  - Chlorophyll fluorescence decay kinetics was measured in sulfur deprived cells of
      green alga Chlamydomonas reinhardtii with a home made picosecond fluorescence
      laser spectrometer. The measurements were carried out on samples either shortly
      adapted to the dark ('Fo conditions') or treated to reduce Qa ('Fm conditions').
      Bi-exponential fitting of decay kinetics was applied to distinguish two
      components one of them related to energy trapping (fast component) and the other
      to charge stabilization and recombination in PS 2 reaction centers (slow
      component). It was found that the slow component yield increased by 2.0 and 1.2
      times when measured under 'Fo' and 'Fm conditions', respectively, in sulfur
      deprived cells as compared to control ones. An additional rapid rise of the slow
      component yield was observed when incubation was carried out in a sealed
      bioreactor and cell culture turned to anaerobic conditions. The obtained results
      strongly indicate the existence of the redox control of PS 2 activity during
      multiphase adaptation of C. reinhardtii to sulfur deficiency stress. Probable
      mechanisms responsible for the observed increased recombinant fluorescence yield
      in starved cells are discussed.

PMID- 17543274
TI  - Surface-active properties of the antitumour ether lipid 1-O-octadecyl-2-O-methyl
      rac-glycero-3-phosphocholine (edelfosine).
AB  - The surface activity and interaction with lipid monolayers and bilayers of the
      antitumour ether lipid 1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine
      (edelfosine) have been studied. Edelfosine is a surface-active soluble
      amphiphile, with critical micellar concentrations at 3.5 microM and 19 microM in
      water. When the air-water interface is occupied by a phospholipid, edelfosine
      becomes inserted in the phospholipid monolayer, increasing surface pressure. This
      increase is dose-dependent, and reaches a plateau at ca. 2 microM edelfosine bulk
      concentration. The ether lipid can become inserted in phospholipid monolayers
      with initial surface pressures of up to 33 mN/m, which ensures its capacity to
      become inserted into cell membranes. Upon interaction with phospholipid vesicles,
      edelfosine exhibits a weak detergent activity, causing release of vesicle
      contents to a low extent (<5%), and a small proportion of lipid solubilization.
      The weak detergent properties of edelfosine can be related to its very low
      critical micellar concentrations. Its high affinity for lipid monolayers combined
      with low lytic properties support the use of edelfosine as a clinical drug. The
      surface-active properties of edelfosine are similar to those of other "single
      chain" lipids, e.g. lysophosphatidylcholine, palmitoylcarnitine, or N
      acetylsphingosine.

PMID- 17543275
TI  - Exploring the evolution of standard amino-acid alphabet: when genomics meets
      thermodynamics.
AB  - One of the most intriguing aspects of life is that despite the diversified
      apparent shapes, similar building blocks and infrastructures, such as standard
      amino acids and canonical genetic codes, are shared by most life on Earth. Thus,
      it is challenging to explore: why nature just selects these building blocks and
      strategies from numerous candidates to construct life? Was this deterministic or
      fortuitous? Thanks to the rapid progress in genomics, bioinformatics and
      synthetic biology, more and more basic principles underlying life design and
      construction were disclosed in the past decade. However, since the origin of
      early life is substantially a chemical process, to understand the enigma of life
      origin, chemists' efforts can not be neglected. In this paper, we focus on the
      evolution of standard amino-acid alphabet and indicate that chemistry, especially
      thermodynamics, is indeed critical to understanding the forming mechanisms of
      amino-acid alphabet. It is revealed that nature prefers low free energy and thus
      ubiquitous (cheap) small amino acids when beginning to build life, which is
      compatible with many recent findings from genomics and bioinformatics.

PMID- 17543276
TI  - Drebrin attenuates the interaction between actin and myosin-V.
AB  - Drebrin-A is an actin-binding protein localized in the dendritic spines of mature
      neurons, and has been suggested to affect spine morphology [K. Hayashi, T.
      Shirao, Change in the shape of dendritic spines caused by overexpression of
      drebrin in cultured cortical neurons, J. Neurosci. 19 (1999) 3918-3925]. However,
      no biochemical analysis of drebrin-A has yet been reported. In this study, we
      purified drebrin-A using a bacterial expression system, and characterized it in
      vitro. Drebrin-A bound to actin filaments with a stoichiometry of one drebrin
      molecule to 5-6 actin molecules. Furthermore, drebrin-A decreased the Mg-ATPase
      activity of myosin V. In vitro motility assay revealed that the attachment of F
      actin to glass surface coated with myosin-V was decreased by drebrin-A, but once
      F-actin attached to the surface, the sliding speed of F-actin was unaffected by
      the presence of drebrin A. These findings suggest that drebrin-A may affect spine
      dynamics, vesicle transport, and other myosin-V-driven motility in neurons
      through attenuating the interaction between actin and myosin-V.

PMID- 17543277
TI  - Cross-talk between the NR3B and NR4A families of orphan nuclear receptors.
AB  - Estrogen-related receptors (NR3B family) and Nurr1, NGFI-B, and Nor1 (NR4A
      family) are orphan nuclear receptors lacking identified natural ligands. The
      mechanisms regulating their transcriptional activities have remained elusive. We
      have previously observed that the members of NR3B and NR4A families are
      coexpressed in certain cell types such as osteoblasts and that the ability of
      Nurr1 to transactivate the osteopontin promoter is repressed by ERRs. We have now
      studied the cross-talk between NR3B and NR4A receptors. We show that NR3B and
      NR4A receptors mutually repress each others' transcriptional activity. The
      repression involves intact DNA-binding domains and dimerization interfaces but
      does not result from competition for DNA binding or from heterodimerization. The
      activation functions of NR3B and NR4A receptors are dispensable for the cross
      talk. In conclusion, we report that cross-talk between NR3B and NR4A receptors is
      a mechanism modulating the transcriptional activities of these orphan nuclear
      receptors.

PMID- 17543278
TI  - LIGHT, a member of the TNF superfamily, activates Stat3 mediated by NIK pathway.
AB  - Stat3, a member of the signal transducers and activators of transcription (STAT)
      family, is a key signal transduction protein activated by numerous cytokines,
      growth factors, and oncoproteins that controls cell proliferation,
      differentiation, development, survival, and inflammation. Constitutive activation
      of Stat3 has been found frequently in a wide variety of human tumors and induces
      cellular transformation and tumor formation. In this study, we demonstrated that
      LIGHT, a member of tumor necrosis factor superfamily, activates Stat3 in cancer
      cells. LIGHT induces dose-dependent activation of Stat3 by phosphorylation at
      both the tyrosine 705 and serine 727 residues. The activation of Stat3 by LIGHT
      appears to be mediated by NIK phosphorylation. Expression of a kinase-inactive
      NIK mutant abolished LIGHT induced Stat3 activation. Overexpression of an active
      NIK induces Stat3 activation by phosphorylation at the both tyrosine 705 and
      serine 727 residues. Activation of Stat3 by NIK requires NIK kinase activity as
      showed by kinase assays. In addition, LIGHT increases the expression of Stat3
      target genes including cyclin D1, survivin, and Bcl-xL, and stimulates human
      LNCaP prostate cancer cell growth in vitro which can be blocked by expression of
      a dominant-negative Stat3 mutant. Taken together, these results indicate that in
      addition to activating NF-kappaB/p52, LIGHT also activates Stat3. Activation of
      Stat3 together with activating non-canonical NF-kappaB/p52 signaling by LIGHT may
      maximize its effects on cellular proliferation, survival, and inflammation.

PMID- 17543279
TI  - Ghrelin inhibits apoptosis signal-regulating kinase 1 activity via upregulating
      heat-shock protein 70.
AB  - Ghrelin is an endogenous ligand of the growth hormone secretagogue receptor (GHS
      R), which has been originally isolated from rat stomach. It has been reported
      that ghrelin inhibited apoptosis in several cells, such as cardiomyocytes,
      endothelial cells, adipocyte, adrenal zona glomerulosa cells, pancreatic beta
      cells, osteoblastic MC3T3-E1 cells, intestinal epithelial cells and hypothalamic
      neurons. However, it is unknown whether heat-shock protein 70 (HSP70) or
      apoptosis signal-regulating kinase 1 (ASK1) is the important target molecule
      which mediates the anti-apoptotic effects of ghrelin. We show that ghrelin
      inhibited ASK1 activity induced by sodium nitroprusside (SNP), inhibited ASK1
      mediated caspase 3 activation and apoptosis in PC12 cells. Ghrelin promoted
      expression of HSP70. Quercetin, an inhibitor of HSP70, blocked the effects of
      ghrelin on ASK1 activity. Thus, ghrelin inhibits ASK1-mediated apoptosis and ASK1
      activation by a mechanism involving induction of HSP70 expression. The results of
      the present study suggest the therapeutic potential of ghrelin for some
      pathological processes or disorders.

PMID- 17543280
TI  - Identification of novel serum proteins in a Japanese viper: homologs of mammalian
      PSP94.
AB  - Three small serum proteins (SSP-1, -2, and -3), with molecular masses of 6.5
      10kDa, were isolated from Habu (Trimeresurus flavoviridis) serum, and the amino
      acid sequences were determined by protein and cDNA analysis. Despite only limited
      sequence identity to any mammalian prostatic secretory protein of 94 amino acids
      (PSP94), all of the Cys residues in these SSPs were well conserved. SSPs are the
      first PSP94 family proteins to be identified in reptiles. SSP-1 and -3 weakly
      inhibited the proteolytic activity of a snake venom metalloproteinase. On the
      other hand, SSP-2 formed a tight complex with triflin, a snake venom-derived
      Ca(2+) channel blocker that suppresses the smooth muscle contraction. This
      suggests a role for SSP-2 in the self defense system of venomous snakes.

PMID- 17543281
TI  - Analysis of the material properties of early chondrogenic differentiated adipose
      derived stromal cells (ASC) using an in vitro three-dimensional micromass culture
      system.
AB  - Cartilage is an avascular tissue with only a limited potential to heal and
      chondrocytes in vitro have poor proliferative capacity. Recently, adipose-derived
      stromal cells (ASC) have demonstrated a great potential for application to tissue
      engineering due to their ability to differentiate into cartilage, bone, and fat.
      In this study, we have utilized a high density three-dimensional (3D) micromass
      model system of early chondrogenesis with ASC. The material properties of these
      micromasses showed a significant increase in dynamic and static elastic modulus
      during the early chondrogenic differentiation process. These data suggest that
      the 3D micromass culture system represents an in vitro model of early
      chondrogenesis with dynamic cell signaling interactions associated with the
      mechanical properties of chondrocyte differentiation.

PMID- 17543282
TI  - Role of H(abc) domain in membrane trafficking and targeting of syntaxin 1A.
AB  - Membrane syntaxin plays essential roles in exocytosis in eukaryotic cells. The
      conservative H(abc) domain in plasma membrane syntaxins implies important roles
      for syntaxin targeting and function. Our previous study showed H(abc) domain was
      necessary for the trafficking and cluster distribution of syntaxin 1A on the
      plasma membrane. Here we identified which of the three domains (H(a), H(b) and
      H(c)) was essential for Stx1A trafficking and clustering. We found that, in INS-1
      cells, the mutant truncated with either H(a), H(b) or H(c) domain could be sorted
      to the cell surface by a different mechanism compared to that of whole H(abc)
      truncated mutant. In contrast to wild type Stx1A, none of the mutants showed
      cluster distribution at the functional sites, suggesting that the physiological
      localization of Stx1A relies on intact H(abc) domain. Furthermore Munc18-1 is
      found not to be essential for Stx1A cluster distribution, despite important role
      in stabilizing membrane delivery of Stx1A.

PMID- 17543283
TI  - Fibroblast growth factor-2 stimulates adipogenic differentiation of human adipose
      derived stem cells.
AB  - Adipose-derived stem cells (ASCs) have demonstrated a capacity for
      differentiating into a variety of lineages, including bone, cartilage, or fat,
      depending on the inducing stimuli and specific growth and factors. It is
      acknowledged that fibroblast growth factor-2 (FGF-2) promotes chondrogenic and
      inhibits osteogenic differentiation of ASCs, but thorough investigations of its
      effects on adipogenic differentiation are lacking. In this study, we demonstrate
      at the cellular and molecular levels the effect of FGF-2 on adipogenic
      differentiation of ASCs, as induced by an adipogenic hormonal cocktail consisting
      of 3-isobutyl-1-methylxanthine (IBMX), dexamethasone, insulin, and indomethacin.
      FGF-2 significantly enhances the adipogenic differentiation of human ASCs.
      Furthermore, in cultures receiving FGF-2 before adipogenic induction, mRNA
      expression of peroxisome proliferator-activated receptor gamma2 (PPARgamma2), a
      key transcription factor in adipogenesis, was upregulated. The results of FGF-2
      supplementation suggest the potential applications of FGF-2 and ASCs in adipose
      tissue regeneration.

PMID- 17543284
TI  - Structural divergence of GPI-80 in activated human neutrophils.
AB  - GPI-80 is a glycosylphosphatidylinositol (GPI)-anchored protein that is mainly
      expressed in human neutrophils. Previous studies using 3H9, a monoclonal antibody
      (mAb) against GPI-80, suggested that GPI-80 regulates leukocyte adherence and
      migration through Mac-1. GPI-80, which is anchored at the plasma membrane in
      resting neutrophils, moves into the pseudopodia and is released from activated
      human neutrophils. Here, we demonstrate that neutrophil activation affects GPI-80
      dynamics using a new anti-GPI-80 mAb, designated 4D4, which is directed against
      the form of GPI-80 found on resting human neutrophils. Similar to 3H9, 4D4
      influences Mac-1-dependent neutrophil adhesion. Treatment of purified GPI-80 with
      periodic acid and trypsin indicated that 3H9 and 4D4 recognize peptide and
      carbohydrate moieties, respectively. Stimulation with fMLP decreased the binding
      of 4D4 to GPI-80 on the neutrophil surface but increased the overall expression
      of GPI-80, as visualized by the 3H9 signal. Confocal laser microscopy revealed
      the 4D4 signal mainly on cell bodies and at a low level on pseudopodia during
      migration toward increasing concentrations of fMLP, whereas the 3H9 signal was
      observed in both areas. In addition, soluble GPI-80 released from activated
      neutrophils did not bind 4D4. These results suggest that there are two
      populations of GPI-80 that differ in the ability to bind 4D4. The 4D4-recognized
      form may regulate Mac-1-dependent neutrophil adhesion, and may subsequently be
      converted to a 4D4-unrecognized form during neutrophil activation.

PMID- 17543285
TI  - Visfatin is released from 3T3-L1 adipocytes via a non-classical pathway.
AB  - Visfatin is a secretory protein which exerts insulin mimetic and proinflammatory
      effects, also functioning as an intracellular enzyme to produce NAD. Plasma
      visfatin levels and visfatin mRNA expression in adipose tissues are increased in
      obese subjects. Visfatin does not have a decent cleavable signal sequence, and
      the mechanism, that mediates release of visfatin from adipocytes, remains poorly
      understood. In this study, we demonstrate that visfatin is released abundantly
      into culture medium from 3T3-L1 adipocytes. Subcellular fractionation analysis
      showed that visfatin was localized in the cytosol, but not in nucleus, membrane,
      vesicles, or mitochondria fractions. Visfatin release was not reduced by
      Brefeldin A and Monensin, inhibitors of endoplasmic reticulum (ER)-Golgi
      dependent secretion. In addition, visfatin was not released on microvesicles.
      These results suggest that visfatin should be released from 3T3-L1 adipocytes via
      an ER-Golgi or microvesicles independent pathway.

PMID- 17543286
TI  - The roles of mesenchymal stem cells (MSCs) therapy in ischemic heart diseases.
AB  - Growing cell-based myocardial therapies which could lead to successful myocardial
      repair attracts medical interest. Even more intriguing is the observation that
      MSCs appears to be a more potent material among kinds of stem cells for the
      transplantation, the mechanism for this benefit remains unclear. However, the
      therapeutic contribution of MSCs to myocardial repair can be caused by multiple
      factors including: direct differentiation into cardiac tissue including
      cardiomyocytes, smooth muscle cell, and vascular endothelial cells; secreting a
      variety of cytokines and growth factors that have paracrine activities;
      spontaneous cell fusion; and stimulating endogenous repair. In addition, MSCs
      possess local immunosuppressive properties, and MSCs mobilization is widely used
      clinically for transplantation. We will discusses the potential mechanisms of
      MSCs repair for ischemic heart diseases.

PMID- 17543287
TI  - Effect of diadenosine polyphosphates in achondroplasic chondrocytes: inhibitory
      effect of Ap4A on FGF9 induced MAPK cascade.
AB  - Achondroplasia is characterised by a mutation in the gene that encodes for the
      FGF receptor type 3 (FGFR3), producing a hyperactivation of this receptor and a
      subsequent increase in MAPK activity. We have tested the ability of nucleotides
      to decrease the activation of MAPK in chondrocytes with achondroplasic FGFR3
      receptor. Diadenosine tetraphosphate, Ap(4)A, reduced the phosphorylation of
      pERK1/2 triggered by FGF9 (38% reduction). Ap(4)A diminished the expression of
      achondroplasic FGFR3 receptor (65% reduction), stimulating FGFR3 receptor
      degradation. The action of Ap(4)A seems to be mediated by a dinucleotide receptor
      rather than by any other ATP receptor.

PMID- 17543288
TI  - The neurocognitive signature of psychotic bipolar disorder.
AB  - BACKGROUND: Psychotic bipolar disorder may represent a neurobiologically distinct
      subgroup of bipolar affective illness. We sought to ascertain the profile of
      cognitive impairment in patients with bipolar disorder and to determine whether a
      distinct profile of cognitive deficits characterizes bipolar patients with a
      history of psychosis. METHODS: Sixty-nine outpatients with bipolar I disorder (34
      with a history of psychotic symptoms and 35 with no history of psychosis) and 35
      healthy comparison subjects underwent a comprehensive neurocognitive battery. All
      three groups were demographically matched. RESULTS: Despite preserved general
      intellectual function, bipolar I patients overall showed moderate impairments on
      tests of episodic memory and specific executive measures (average effect size =
      .58), and moderate to severe deficits on attentional and processing speed tasks
      (average effect size = .82). Bipolar I patients with a history of psychosis were
      impaired on measures of executive functioning and spatial working memory compared
      with bipolar patients without history of psychosis. CONCLUSIONS: Psychotic
      bipolar disorder was associated with differential impairment on tasks requiring
      frontal/executive processing, suggesting that psychotic symptoms may have neural
      correlates that are at least partially independent of those associated with
      bipolar I disorder more generally. However, deficits in attention, psychomotor
      speed, and memory appear to be part of the broader disease phenotype in patients
      with bipolar disorder.

PMID- 17543289
TI  - Sleep findings in young adult patients with posttraumatic stress disorder.
AB  - BACKGROUND: Laboratory sleep studies in posttraumatic stress disorder (PTSD) have
      not provided consistent evidence of sleep disturbance, despite apparent sleep
      complaints. Most of these studies have investigated middle-aged chronic PTSD
      subjects with a high prevalence of comorbidities such as substance dependence
      and/or personality disorder. METHODS: Ten young adult PTSD patients (aged 23.4 +/
      6.1 years) without comorbidities of substance dependence and/or personality
      disorder underwent 2-night polysomnographic recordings. These sleep measures were
      compared with those of normal control subjects and were correlated with PTSD
      symptoms. RESULTS: Posttraumatic stress disorder patients demonstrated
      significantly poorer sleep, reduced sleep efficiency caused by increased wake
      time after sleep onset, and increased awakening from rapid eye movement (REM)
      sleep (REM interruption). We found significant positive correlations between the
      severity of trauma-related nightmare complaints and the percentage of REM
      interruption, as well as wake time after sleep onset. CONCLUSIONS: The results
      indicate that trauma-related nightmares are an important factor resulting in
      increased REM interruptions and wake time after sleep onset in PTSD.

PMID- 17543290
TI  - Experimental intracerebral hematoma in the rat: characterization by sequential
      magnetic resonance imaging, behavior, and histopathology. Effect of albumin
      therapy.
AB  - We characterized acute intracerebral hemorrhage (ICH) in the rat by sequential
      magnetic resonance imaging (MRI) and correlated MRI findings with neurobehavior
      and histopathology. In addition, we investigated whether albumin treatment would
      reduce ICH-induced brain injury. ICH was produced in rats by a double-injection
      method in which 45 microl of fresh arterial blood was injected into the right
      striatum. Susceptibility-weighted (SWI) and T2-weighted (T2WI) MRI was carried
      out on a 4.7T magnet at 0-1 h, 6 h, 24 h, 72 h, and 7 days after ICH. Animals
      were treated with either 25% human albumin, 1.25 g/kg, or saline vehicle i.v. at
      90 min after ICH. Neurological status was evaluated before ICH and after
      treatment (at 4 h, 24 h, 48 h, 72 h, and 7 days). Brains were then perfusion
      fixed, re-imaged on an 11.7T magnet, and studied by histopathology and
      immunochemistry. MRI revealed a consistent hematoma involving the striatum and
      overlying corpus callosum, with significant volume changes over time. Lesion
      volumes computed from T2WI images and by histopathology agreed closely with one
      another and were highly correlated (p=0.002). SWI lesion volumes were also highly
      correlated to histological volumes (p<0.001) but overestimated histological
      hematoma volume by approximately 5-fold. Albumin treatment significantly improved
      neurological scores compared to saline at 72 h (3.8+/-0.6 vs. 1.5+/-0.7) and 7
      days (3.8+/-0.4 vs. 1.3+/-0.5, respectively, p<0.05), but did not affect
      histological or MRI lesion volumes. Taken together, sequential MRI plus
      histopathology provides a comprehensive characterization of experimental ICH.
      Albumin treatment improves neurological deficit after ICH but does not affect MRI
      or histological hematoma size.

PMID- 17543291
TI  - Human motor cortex oxygenation during exhaustive pinching task.
AB  - There are few observations of the activity of the bilateral motor cortex during
      prolonged exhaustive motor tasks. Knowing how the motor cortex modulates muscle
      fatigue or how information about fatigue affects motor cortex activities in
      healthy humans may help explain why fatigue is so prevalent in patients with
      neurological disorders. The purpose of the present study was to investigate the
      time course of oxygenation of the bilateral motor cortex during an exhaustive
      pinching task. Eight healthy, right-handed subjects participated in the study.
      Near-infrared spectroscopy over the bilateral motor cortex was used to measure
      the activity throughout the pinching task. Subjects performed a sustained 50-60%
      of maximal voluntary contraction until voluntary exhaustion was reached. After
      the start of the motor task, the contralateral motor cortex oxygenation increased
      significantly compared with the resting value (P<0.05). However, with the passage
      of time, it decreased significantly compared with the resting value (P<0.05). In
      addition, ipsilateral motor cortex oxygenation decreased significantly at
      voluntary exhaustion compared with the resting value (P<0.05). These results
      suggest an interaction between the bilateral motor cortices during motor tasks.

PMID- 17543292
TI  - AMPA receptor activation reduces epileptiform activity in the rat neocortex.
AB  - We have previously reported that topical application of alpha-amino-3-hydroxy-5
      methyl-4-isoxazolepropionic acid (AMPA) to the rat neocortex prevents the effects
      of a subsequent application of N-methyl-d-aspartic acid (NMDA). Activation of
      NMDA receptors is involved in the pathogenesis of epileptic activity. Therefore,
      we examined if topically applied AMPA could affect changes in the somatosensory
      evoked potentials (SEPs) and electrocorticogram (ECoG) epileptic spikes caused by
      bicuculline. AMPA (50 microM) prevented the epileptiform activity to a level that
      was comparable to that caused by diazepam (3 mg/kg i.p.) or clomethiazole (100
      mg/kg i.p.). Also, the epileptiform activity was suppressed by the AMPAR
      antagonist, CNQX, or the blocker of AMPAR desensitization, cyclothiazide. In the
      hippocampal slice, bicuculline-induced changes in the population spike potentials
      recorded from the CA1 cells were not affected by AMPA. We conclude that in the
      complex neuronal network of the rat neocortex, epileptiform activity can be
      suppressed in a variety of strategies that target the AMPA receptors: (1)
      blocking AMPA receptors, (2) promoting an apparent desensitization of AMPA
      receptors (possibly on the pyramidal neurons) or (3) reducing an apparent
      desensitization of AMPA receptors (possibly on the inhibitory GABA-ergic
      interneurons).

PMID- 17543293
TI  - Prenatal restraint stress and motherless rearing disrupts expression of
      plasticity markers and stress-induced corticosterone release in adult female
      Sprague-Dawley rats.
AB  - This study investigated the effects of prenatal stress and complete maternal
      deprivation, using the artificial rearing (AR) paradigm, on the expression of
      neural plasticity markers and hypothalamic-pituitary-adrenal (HPA) axis
      responsivity to stress. Rats were exposed to stress during gestation (day 10-21)
      and postnatally were either artificially reared (AR) or mother reared (MR). AR
      involves complete separation of the pup from both the dam and the litter
      throughout the pre-weaning period. In adulthood, we measured levels of
      corticosterone (CORT) in response to restraint stress. Also, we examined the
      expression of synaptophysin (SYN) and brain-derived neurotrophic factor (BDNF) in
      the medial prefrontal cortex (MPFC) and the nucleus accumbens (Nacc), areas of
      the brain that mediate behavioral activation and attention, among other
      behaviors. Earlier work on the same rats indicated that these behavioral
      endpoints, such as locomotor activity and sensorimotor gating, are affected by
      our prenatal and postnatal manipulations. Prenatal stress decreased CORT at 20
      and 90 min post-stressor in MR, but not in AR, animals. Also, in comparison to MR
      groups, AR decreased SYN and BDNF expression in the MPFC and Nacc. Additional
      somatosensory 'licking-like' stroking stimulation partially reversed the effects
      of AR. Prenatal stress did not have a robust main effect but affected the impact
      of the postnatal rearing condition on SYN expression and stress-induced CORT.
      These results suggest that both prenatal and postnatal adversities have an
      influence on HPA axis responsivity and alter the expression of plasticity related
      neuronal proteins.

PMID- 17543294
TI  - Pre- and post-initiation chemoprevention activity of 2-alkyl/aryl selenazolidine
      4(R)-carboxylic acids against tobacco-derived nitrosamine (NNK)-induced lung
      tumors in the A/J mouse.
AB  - The efficacy of a series of 2-aryl/alkyl selenazolidine-4(R)-carboxylic acids
      (SCAs) in reducing NNK [4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone]-induced
      lung adenomas in female A/J mice, a model for tobacco-related lung tumorigenesis,
      has been investigated. With selenazolidines in the diet for 1 month prior to
      carcinogen administration and during the subsequent 4 months of tumor
      development, 2-butylSCA, 2-cyclohexylSCA, 2-phenylSCA and 2-oxoSCA were
      chemopreventive, significantly reducing mean lung tumor numbers from the 10.9 of
      unsupplemented controls to 4.7, 5.3, 2.8 and 4.7, respectively. When
      selenazolidine supplementation began three days after carcinogen administration
      (i.e., post-initiation), 2-butylSCA, 2-cyclohexylSCA, and 2-oxoSCA were
      chemopreventive. In both regimens, selenocystine was also chemopreventive. In the
      post-initiation protocol, but with intervention at a precancerous stage (13
      days), whole genome expression analysis of lung RNA identified six gene
      transcripts that weakly correlated with the efficacy of tumor reduction by the
      four selenocompounds at 4 months. None of these genes were among those identified
      to be influenced by chemopreventive selenium compounds in human lung cancer cell
      lines. When supplementation was for 1 month-prior until 3 days-after carcinogen
      administration, 2-butylSCA, and 2-phenylSCA were chemopreventive but
      selenocystine was ineffective. Both 2-butylSCA and 2-phenylSCA retained their
      chemopreventive activity (44% and 40% tumor number reduction, respectively), when
      the supplementation was shortened and restricted to a pre-initiation period (days
      -9 to -2). With supplementation spanning 2 days-prior until 3 days-after NNK,
      reductions in tumor numbers by 2-phenylSCA (26%) and 2-butylSCA (17%) did not
      achieve statistical significance. Thus, several 2-aryl/alkyl selenazolidines
      possess chemopreventive activity against NNK-induced lung tumors, and variously
      demonstrate pre-initiation and post-initiation efficacy.

PMID- 17543295
TI  - Therapeutic potential of bone marrow-derived mesenchymal stem cells on
      experimental liver fibrosis.
AB  - OBJECTIVE: To study the effect of mesenchymal stem cells (MSC) on experimental
      liver fibrosis in rats. DESIGN AND METHOD: MSC were derived from bone marrow
      obtained from femoral and tibial bones of male albino rats. MSC were separated,
      grown, and propagated in culture for 4 weeks and were characterized
      morphologically and by detection of CD29 by RT-PCR. They were then infused into
      the tail vein of female rats that received CCl4 injection to induce liver
      fibrosis. Rats were divided into 4 groups: control, CCl4, CCl4 plus MSC, and MSC.
      Liver tissue was examined histopathologically and liver functions (ALT and serum
      albumin) were estimated for all groups. Y-chromosome gene (sry) was assessed by
      PCR in liver tissue of the female rats to confirm uptake of the male stem cells.
      Hydroxyproline content in liver tissue was assessed by chemical methods and
      expression of the collagen gene (type I) was detected as a marker for liver
      fibrosis. Results of the present study showed that MSC have a significant
      antifibrotic effect as evidenced by the significant decrease in liver collagen
      gene expression as well as the decrease in hydroxyproline content in the CCl4/MSC
      group (p<0.001) compared to the CCl4 group. The Y-chromosome gene (sry) was
      detected by RT-PCR in the CCl4/MSC group, but was not detected in control group
      and other groups. The CD29 gene was expressed in MSC culture, and this confirmed
      the efficiency of isolation and propagation of MSC in culture. With regard to
      liver function, there was also a significant improvement and elevation of serum
      albumin in the CCl4/MSC group compared to the CCl4 group (p<0.05). As regard to
      the liver enzyme ALT, there was a decrease of its level in the CCl4/MSC group
      compared to the CCl4 group. However, this was statistically nonsignificant
      (p>0.05). In conclusion, MSC have a potential therapeutic effect against the
      fibrotic process through their effect in minimizing collagen deposition in
      addition to their capacity to differentiate into hepatocytes.

PMID- 17543296
TI  - Can tissue surface tension drive somite formation?
AB  - The prevailing model of somitogenesis supposes that the presomitic mesoderm is
      segmented into somites by a clock and wavefront mechanism. During segmentation,
      mesenchymal cells undergo compaction, followed by a detachment of the presumptive
      somite from the rest of the presomitic mesoderm and the subsequent morphological
      changes leading to rounded somites. We investigate the possibility that
      minimization of tissue surface tension drives the somite sculpting processes.
      Given the time in which somite formation occurs and the high bulk viscosities of
      tissues, we find that only small changes in shape and form of tissue typically
      occur through cell movement driven by tissue surface tension. This is
      particularly true for somitogenesis in the zebrafish. Hence it is unlikely that
      such processes are the sole and major driving force behind somite formation. We
      propose a simple chemotactic mechanism that together with heightened adhesion can
      account for the morphological changes in the time allotted for somite formation.

PMID- 17543297
TI  - Essential role of lysyl oxidases in notochord development.
AB  - Recent studies reveal a critical role for copper in the development of the
      zebrafish notochord, suggesting that specific cuproenzymes are required for the
      structural integrity of the notochord sheath. We now demonstrate that beta
      aminopropionitrile, a known inhibitor of the copper-dependent lysyl oxidases,
      causes notochord distortion in the zebrafish embryo identical to that seen in
      copper deficiency. Characterization of the zebrafish lysyl oxidase genes reveals
      eight unique sequences, several of which are expressed in the developing
      notochord. Specific gene knockdown demonstrates that loss of loxl1 results in
      notochord distortion, and that loxl1 and loxl5b have overlapping roles in
      notochord formation. Interestingly, while notochord abnormalities are not
      observed following partial knockdown of loxl1 or loxl5b alone, in each case this
      markedly sensitizes developing embryos to notochord distortion if copper
      availability is diminished. Likewise, partial knockdown of the lysyl oxidase
      substrate col2a1 results in notochord distortion when combined with reduced
      copper availability or partial knockdown of loxl1 or loxl5b. These data reveal a
      complex interplay of gene expression and nutrient availability critical to
      notochord development. They also provide insight into specific genetic and
      nutritional factors that may play a role in the pathogenesis of structural birth
      defects of the axial skeleton.

PMID- 17543298
TI  - Cyclooxygenase-2 inhibitor ameliorates ureteric damage in rats with obstructed
      uropathy.
AB  - To investigate the effect of cyclooxygenase-2 (COX-2) inhibitor on the tissue
      damage and fibrosis in obstructed ureters, 80 rats were studied. Celecoxib, a COX
      2 inhibitor, was administered to 40 rats at the dose of 10 mg/kg per day 1 day
      before unilateral ligation of ureters and every day thereafter. The others,
      receiving unilateral ligation of ureters only, served as controls. Eight rats
      from each group were sacrificed for examination on days 7, 14, 21, 28 and 42
      after ligation, respectively. The expressions of COX-2, prostaglandin E(2)
      (PGE(2)), transforming growth factor-beta(1) (TGFbeta(1)), alpha-smooth muscle
      actin (alpha-SMA), proliferation cell nuclear antigen (PCNA) and the apoptotic
      cells in the ureteric smooth muscle were examined. Hydroureter and fibrosis of
      the muscle layer became progressively aggravated during the period of obstruction
      in the ligated ureters of both groups. The severity of the hydroureter and
      fibrosis of muscle layer in the ligated ureters of the treated group was
      significantly milder than those of the control group. Expressions of COX-2 and
      PGE(2) were found in the smooth muscle layer of ligated ureters in the control
      group from day 14 after ureteric ligation, reached a peak on day 21, and then
      declined. Treatment with Celecoxib completely abolished the expression of COX-2
      and PGE(2). The Celecoxib administration also decreased the expression of
      TGFbeta(1), alpha-SMA and the labeling index of apoptotic cells in the smooth
      muscle layer of ligated ureters in the treated group. In the contrast, treatment
      with Celecoxib significantly increased the expression of PCNA in the smooth
      muscle layer of ligated ureters in the treated group. We concluded that COX-2
      inhibitor might ameliorate the damage of obstructed ureters, at least partly, via
      the inhibition of COX-2 and TGFbeta(1) expression.

PMID- 17543299
TI  - Reorganization of dorsal root ganglion neurons following chronic sciatic nerve
      constriction injury: correlation with morphine and lidocaine analgesia.
AB  - Chronic constriction injury of the sciatic nerve is an animal model for
      neuropathic pain. In this model, the analgesic potency of systemic morphine was
      significantly diminished in nerve-injured mice (ED(50) 19.4 mg/kg) compared with
      sham-operated mice (ED(50) 3.3 mg/kg) using a unilateral hot plate withdrawal
      test, with a similar reduction in sensitivity of intrathecal morphine. The
      sciatic nerve injury resulted in a reorganization of the dorsal root ganglion
      (DRG) neurons. Immunohistochemically, the chronic constriction injury triggered a
      withdrawal of C-fibers from the ipsilateral dorsal horn of the spinal cord.
      Although A-beta terminals centrally sprouted into Lamina II of the dorsal horn of
      the spinal cord, the peripheral A-beta fibers in the skin retracted from the
      epidermis to deeper layers of the dermis. To explore the functional significance
      of these dermal changes, we examined the topical morphine and lidocaine analgesia
      following chronic sciatic nerve constriction. Both morphine and lidocaine
      retained topical activity following chronic sciatic nerve injury, but their
      analgesic dose-response curves were shifted to the right when compared to sham
      operated mice. Thus, the chronic nerve constriction injury model is associated
      with pathological changes in distribution of the central and peripheral axons of
      the dorsal root ganglion neurons that correspond to a decreased pharmacological
      sensitivity to topical analgesic agents.

PMID- 17543300
TI  - Involvement of chemical mediators in nasal allergic responses of HDC-KO mice.
AB  - The present study was undertaken to investigate the involvement of chemical
      mediators in nasal allergic responses using histidine decarboxylase knockout (HDC
      KO) mice. An allergic rhinitis model was developed in HDC-KO and wild-type mice
      by the intraperitoneal injection of ovalbumin, aluminum hydroxide gel and
      pertussis toxin. Five days later, they were boosted by a subcutaneous injection
      of ovalbumin into the back. From day 18 after the first immunization to day 39,
      intranasal sensitization with ovalbumin was performed every day and the severity
      of allergic rhinitis was observed by measuring nasal allergic responses and total
      IgE levels. It was found that the intranasal administration of antigen caused a
      significant increase of nasal sneezing and rubbing from day 25 to day 39 both in
      sensitized HDC-KO and wild-type mice. In addition, a significant elevation of
      total IgE levels in serum was also found both in sensitized HDC-KO and wild-type
      mice from day 18 to day 39 after the first immunization. L-733,060, a tachykinin
      NK(1) receptor antagonist at a dose of 10 mg/kg (s.c.), resulted in the dose
      dependent inhibition of nasal allergic responses induced by antigen in both HDC
      KO and wild-type mice. In addition, both chlorpheniramine at doses of 3 and 10
      mg/kg (p.o.) and BW A868C at doses of 0.3 and 1 mg/kg (i.v.) also showed a dose
      related reduction of the nasal allergic responses induced by antigen in
      sensitized wild-type mice. On the other hand, they had no effects on the nasal
      signs induced by antigen in HDC-KO mice. From these results, it was revealed that
      substance P induces nasal allergic responses in the mouse model of chronic
      allergic rhinitis through the activation of tachykinin NK(1) receptors.
      Therefore, it can be concluded that not only histamine, but also substance P and
      prostaglandin D(2), participated in the nasal allergic responses induced by
      antigen in mice.

PMID- 17543301
TI  - Isolated Anxa5+/Sca-1+ perivascular cells from mouse meningeal vasculature retain
      their perivascular phenotype in vitro and in vivo.
AB  - Pericytes are closely associated with endothelial cells, contribute to vascular
      stability and represent a potential source of mesenchymal progenitor cells. Using
      the specifically expressed annexin A5-LacZ fusion gene (Anxa5-LacZ), it became
      possible to isolate perivascular cells (PVC) from mouse tissues. These cells
      proliferate and can be cultured without undergoing senescence for multiple
      passages. PVC display phenotypic characteristics of pericytes, as they express
      pericyte-specific markers (NG2-proteoglycan, desmin, alphaSMA, PDGFR-beta). They
      also express stem cell marker Sca-1, whereas endothelial (PECAM), hematopoietic
      (CD45) or myeloid (F4/80, CD11b) lineage markers are not detectable. These
      characteristics are in common with the pericyte-like cell line 10T1/2. PVC also
      display a phagocytoic activity higher than 10T1/2 cells. During coculture with
      endothelial cells both cell types stimulate angiogenic processes indicated by an
      increased expression of PECAM in endothelial cells and specific deposition of
      basement membrane proteins. PVC show a significantly increased induction of
      endothelial specific PECAM expression compared to 10T1/2 cells. Accordingly, in
      vivo grafts of PVC aggregates onto chorioallantoic membranes of quail embryos
      recruit endothelial cells, get highly vascularized and deposit basement membrane
      components. These data demonstrate that isolated Anxa5-LacZ(+) PVC from mouse
      meninges retain their capacity for differentiation to pericyte-like cells and
      contribute to angiogenic processes.

PMID- 17543302
TI  - Involvement of TR3/Nur77 translocation to the endoplasmic reticulum in ER stress
      induced apoptosis.
AB  - Nuclear orphan receptor TR3/Nur77/NGFI-B is a novel apoptotic effector protein
      that initiates apoptosis largely by translocating from the nucleus to the
      mitochondria, causing the release of cytochrome c. However, it is possible that
      TR3 translocates to other organelles. The present study was designed to determine
      the intracellular localization of TR3 following CD437-induced nucleocytoplasmic
      translocation and the mechanisms involved in TR3-induced apoptosis. In human
      neuroblastoma SK-N-SH cells and human esophageal squamous carcinoma EC109 and
      EC9706 cells, 5 microM CD437 induced translocation of TR3 to the endoplasmic
      reticulum (ER). This distribution was confirmed by immunofluorescence analysis,
      subcellular fractionation analysis and coimmunoprecipitation analysis. The
      translocated TR3 interacted with ER-targeting Bcl-2; initiated an early release
      of Ca(2+) from ER; resulted in ER stress and induced apoptosis through ER
      specific caspase-4 activation, together with induction of mitochondrial stress
      and subsequent activation of caspase-9. Our results identified a novel
      distribution of TR3 in the ER and defined two parallel mitochondrial- and ER
      based pathways that ultimately result in apoptotic cell death.

PMID- 17543303
TI  - Babesia bovis: effects of cysteine protease inhibitors on in vitro growth.
AB  - In the present study, we examined the effects of four kinds of cysteine protease
      inhibitors (E64, E64d, leupeptin, and ALLN) on the in vitro asexual growth of
      Babesia bovis. Of these, only the lipophilic inhibitors, E64d and ALLN, were
      found to effectively inhibit the growth of B. bovis. In further experiments,
      E64d, but not ALLN, significantly suppressed the parasite's invasion of host
      erythrocytes, while both chemicals, especially ALLN, inhibited the parasite's
      replication within the infected erythrocytes. These data suggested the presence
      of cysteine protease(s) derived from B. bovis, in which the protease(s) would
      play important roles in the erythrocyte invasion and/or replication processes of
      the parasite.

PMID- 17543304
TI  - Babesia gibsoni: detection during experimental infections and after combined
      atovaquone and azithromycin therapy.
AB  - Babesia gibsoni is a protozoan parasite of dogs worldwide yet both an effective
      treatment and a reliable method for detecting subclinical cases of this emerging
      infection remain elusive. Experimental B. gibsoni infections were established in
      vivo to investigate the efficacy of combined atovaquone and azithromycin drug
      therapy and to determine the detection limits of a nested-PCR, IFAT and
      microscopy during various stages of infection. While atovaquone and azithromycin
      produced a reduction in parasitaemia, it did not eliminate the parasite and drug
      resistance appeared to develop in one dog. Polymerase chain reaction was found to
      be most useful in detecting infection in the pre-acute and acute stages, while
      IFAT was most reliable during chronic infections. Microscopy is suggested to be
      only effective for detecting acute stage infections. This study also describes
      the detection of B. gibsoni in tissue samples during chronic infections for the
      first time, suggesting possible sequestration of this parasite.

PMID- 17543305
TI  - Carboxy terminal extended phytocystatins are bifunctional inhibitors of papain
      and legumain cysteine proteinases.
AB  - Plant legumains are cysteine proteinases putatively involved in processing
      endogenous proteins. Phytocystatins (PhyCys) have been described as plant
      inhibitors of papain-like cysteine proteinases. Some PhyCys contain a carboxy
      terminal extension with an amino acid motif (SNSL) similar to that involved in
      the inhibition of legumain-like proteins by human cystatins. The role of these
      carboxy terminal extended PhyCys as inhibitors of legumain-like cysteine
      proteinases is here shown by in vitro inhibition of human legumain and legumain
      like activities from barley extracts. Moreover, site-directed mutagenesis has
      demonstrated that the asparagine of the SNSL motif is essential in this
      inhibition. We prove for first time the existence of legumain inhibitors in
      plants.

PMID- 17543306
TI  - Inhibition of microglial fatty acid amide hydrolase modulates LPS stimulated
      release of inflammatory mediators.
AB  - Anandamide and other fatty acid amides are metabolised by the enzyme fatty acid
      amide hydrolase (FAAH), which thereby regulates their endogenous levels. Here we
      demonstrate that cultured rat cortical microglia express FAAH at low levels. The
      potent FAAH inhibitor URB597 reduced the LPS stimulated microglial expression of
      cyclo-oxygenase 2 and inducible nitric oxide, with concomitant attenuation of the
      release of PGE2 and NO. Additional of supplemental exogenous anandamide did not
      increase the magnitude of attenuation of mediator release. The effect of URB597
      on LPS stimulated PGE2 release was not blocked by selective CB1 or CB2 receptor
      antagonists.

PMID- 17543307
TI  - EUS for detection of the hepatocellular carcinoma: results of a prospective
      study.
AB  - BACKGROUND: Early detection of hepatocellular carcinoma (HCC) and accurate
      determination of the number of lesions are critical in determining eligibility
      for liver transplantation or resection. Current diagnostic modalities (CT and
      magnetic resonance imaging [MRI]) often miss small lesions. OBJECTIVE: To compare
      the accuracy of the EUS with CT for the detection of primary tumors of the liver.
      DESIGN: Prospective single-center study. SETTING: Academic medical center.
      PATIENTS: Subjects at high risk of HCC (hepatitis B, hepatitis C, or alcoholic
      cirrhosis) were enrolled. INTERVENTIONS: US, CT, MRI, and EUS examinations of the
      liver were performed. Liver lesions identified during EUS underwent EUS-guided
      FNA (EUS-FNA). RESULTS: Seventeen patients were enrolled in the study. Nine of
      these patients had liver tumors (HCC, 8; cholangiocarcinoma, 1). EUS-FNA
      established a tissue diagnosis in 8 of the 9 cases. The diagnostic accuracy of
      US, CT, MRI, and EUS/EUS-FNA were 38%, 69%, 92%, and 94%, respectively. EUS
      detected a significantly higher number of nodular lesions than US (P = .03), CT
      (P = .002), and MRI (P = .04). For HCC lesions, a trend was observed in favor of
      EUS for the detection of more lesions than US (8 vs 2; P = .06) and CT (20 vs 8;
      P = .06). No complications were observed as a result of EUS-FNA. LIMITATIONS:
      Small sample size. CONCLUSIONS: EUS-FNA is a safe and accurate test for the
      diagnosis of HCC. EUS increases the accuracy of intrahepatic staging of the HCC
      by delineation of lesions, which are missed by CT and MRI. We recommend EUS for
      suspected HCC, particularly in cases that are being considered for liver
      transplantation.

PMID- 17543308
TI  - Isolation of pregnancy-associated glycoproteins from placenta of the American
      bison (Bison bison) at first half of pregnancy.
AB  - This paper describes the successful purification and characterisation of
      pregnancy-associated glycoproteins (PAG) extracted from placenta (3-4 months) of
      American bisons (Amb). Chorionic AmbPAG proteins were purified from foetal
      cotyledonary tissues (CT) and liquid cotyledonary-carrying proteins (LCP) leaking
      from damaged cells. Our protocols successfully indicated the usefulness of AmbPAG
      protein identification, especially from LCP fraction. The AmbPAGs were extracted,
      precipitated and eluted during DEAE cellulose chromatography. The richest protein
      fractions were further chromatographed on VVA (Vicia villosa agglutinin affinity
      column), then characterised by mono- and bi-dimensional electrophoresis, Western
      blot and N-terminal amino acid (aa) sequence. After being transferred to PVDF
      membranes, three selected VVA-purified AmbPAG isoforms differing in molecular
      masses and isoelectric points (Ip 4-4.6) were selected for sequencing. One
      identified N-terminal 25aa sequence of AmbPAG72kDa CT form was identified as
      completely new (RGSNLTSLPLQNVIDLFYVGNITIG). Two other AmbPAG proteins purified
      from different sources (74kDa CT and 76kDa LCP forms; RGSNLTIHPLRNIRDIFYVGNITIG)
      were identical or corresponded to N-terminus of various bovine PAGs (boPAG). The
      two AmbPAGs (74kDa CT and 76kDa LCP) revealed identical micro-sequence to boPAG7;
      and were similar mainly to bovine PAG4, -6, -15 and -17 precursors that were
      identified by full-length sequencing derived from cDNA cloning. The novel
      sequence of the AmbPAG (72kDa CT) was related to some boPAG and various other
      ruminant PAG precursors (caprine and ovine). All three identified AmbPAG
      sequences were also relatively similar to mature forms of purified native
      boPAG(56-75kDa) proteins. This is the first report indicating aa sequences of
      native AmbPAG proteins purified from placenta (CT and LCP) of bison species. The
      N-terminal sequences of the AmbPAGs have been deposited in the EMBL-EBI database
      (UniProtKB; Accession Nos.: P84916, P84917 and P84918).

PMID- 17543309
TI  - Endovascular treatment for traumatic injuries of the peripheral arteries
      following blunt trauma.
AB  - OBJECTIVES: The continued advances in imaging and stent/stent-graft technology
      have considerably expanded the indications for endovascular approach also in
      vascular trauma. We report our institutional experience with endovascular
      treatment of peripheral arterial injuries after blunt trauma. METHODS: Between
      January 2000 and June 2006 out of a series of 81 patients, 10 male patients (mean
      age of 50+/-14 years) with peripheral arterial injuries were managed
      endovascularly. At admission, haemorrhagic shock was present in three patients.
      Artery location involved common femoral (n=2), subclavian (n=2), axillary (n=2),
      external iliac (n=2), superficial femoral (n=1), and popliteal (n=1). Type of
      lesion was as follows: pseudoaneurysm (n=4), dissection (n=4), expanding
      haematoma (n=1), and arterio-venous fistula (n=1). Follow-up program included
      visit and duplex-ultrasonography, X-rays and/or spiral-computed tomography at 6
      month interval during the first year, and yearly thereafter. RESULTS: The lesion
      was excluded in all cases. All patients survived. Major complications did not
      occur. Mean hospitalisation was 13 days. Limb-salvage was 100%. Follow-up ranged
      from 3 to 60 months (mean 16); a late occlusion of a popliteal stent-graft was
      managed with another endovascular procedure. CONCLUSION: In our experience,
      endovascular treatment of vascular injuries after blunt trauma was feasible and
      effective.

PMID- 17543310
TI  - Electronic door interference mimicking distress in fetal monitoring.

PMID- 17543311
TI  - Capillary electrophoresis-high resolution sector field inductively coupled plasma
      mass spectrometry.
AB  - The background and applications of high resolution sector field inductively
      coupled plasma mass spectrometry (HR-ICP-MS) as a detector for capillary (CE) and
      gel electrophoretic separations are reviewed. Notable progress has been made in
      the fields of bioinorganic and environmental (geo-) chemistry. Metallomics, the
      study of metal species interactions and functions in biological systems, puts
      substantial technical demands on speciation analysis. The combination of high
      species resolving power (CE) and high sensitivity-high mass resolving power (HR
      ICP-MS) provides a solid base to meet such demands.

PMID- 17543312
TI  - Characterization of the retention behavior of organic and pharmaceutical drug
      molecules on an immobilized artificial membrane column with the Abraham model.
AB  - Data have been compiled from the published literature on the retention factors of
      174 organic compounds and drug molecules eluted from a Regis Technologies
      IAM.PC.DD2 HPLC column using an aqueous mobile phase buffered in the pH range of
      pH 6.5-7.5. The logarithms of the retention factors are correlated with the
      Abraham solvation parameter model. The derived correlation contains the five
      Abraham solute descriptors plus two additional indicator descriptors (I(COOH) and
      I(amine)) that would be needed whenever carboxylic acid and alkylamine solutes
      are eluted in ionic form. The derived correlation describes the experimental
      capacity data of 174 neutral, acidic and basic compounds to within 0.21 log
      units.

PMID- 17543313
TI  - Retention behaviour of polyunsaturated fatty acid methyl esters on porous
      graphitic carbon.
AB  - Retention with porous graphitic carbon was investigated with 25 structures of
      fatty acid methyl esters (FAMEs) with two different mobile phases:
      CH(3)CN:CHCl(3) 60:40 (v/v) and CH(3)OH:CHCl(3) 60:40 (v/v) with both 0.1%
      triethylamine (TEA) and an equimolar amount of HCOOH. Preliminary results showed
      that the use of TEA/HCOOH led to the response increase of saturated FAMEs with
      evaporative light scattering detection. No increase was observed for unsaturated
      one. These modifiers may slightly reduce the retention of FAMEs but did not
      significantly modify the separation factor with porous graphitic carbon.
      Thermodynamic parameters were calculated for each structure using Van't Hoff plot
      measured over the temperature range from 10 to 50 degrees C, with the both mobile
      phase conditions. All the studied compounds were found linked by the same
      retention mechanism on porous graphitic carbon. Quantitative in silico analysis
      of the retention using a molecular mechanics calculation demonstrated a good
      correlation between the retention factors and the molecular interaction energy
      values (r>0.93). Especially the Van der Waals energy was predominant, and the
      contribution of electrostatic energy was negligible for the quantitative analysis
      of the retention. The results indicate that Van der Waals force, hydrophobic
      interaction, is predominant for the retention of FAMEs on this packing material.
      The relative retention for highly unsaturated homologues can be changed by the
      selection of the weak solvent CH(3)CN or CH(3)OH. Then isomers differing only in
      the position of the carbon double bond on the alkyl chain can be separated and
      their behaviour is summarised as the closer the carbon double bonds to the FAME
      polar head, the more the retention decreases. Finally, the more important the
      number of carbon double bonds in the alkyl chain is, the smaller the retention
      is.

PMID- 17543314
TI  - Investigation of the ion-exchange properties of methacrylate-based mixed-mode
      monolithic stationary phases employed as stationary phases in capillary
      electrochromatography.
AB  - The potential of methacrylate-based mixed-mode monolithic stationary phases
      bearing sulfonic acid groups for the separation of positively charged analytes
      (alkylanilines, amino acids, and peptides) by capillary electrochromatography
      (CEC) is investigated. The retention mechanism of protonated alkylanilines as
      positively charged model solutes on these negatively charged mixed-mode
      stationary phases is investigated by studying the influence of mobile phase and
      stationary phase parameters on the corrected retention factor which was
      calculated by taking the electrophoretic mobility of the solutes into
      consideration. It is shown that both solvophobic and ion-exchange interactions
      contribute to the retention of these analytes. The dependence of the corrected
      retention factor on (1) the concentration of the counter ion ammonium and (2) the
      number of methylene groups in the alkyl chain of the model analytes investigated
      shows clearly that a one-site model (solvophobic and ion-exchange interactions
      take place simultaneously at a single type of site) has to be taken to describe
      the retention behaviour observed. Comparison of the CEC separation of these
      charged analytes with electrophoretic mobilities determined by open-tubular
      capillary electrophoresis shows that mainly chromatographic interactions
      (solvophobic and ion-exchange interactions) are responsible for the selectivity
      observed in CEC, while the electrophoretic migration of these analytes plays only
      a minor role.

PMID- 17543315
TI  - Development of a database of gas chromatographic retention properties of organic
      compounds.
AB  - A comprehensive database of gas chromatographic retention properties of chemical
      compounds has been developed using multiple literature sources. The National
      Institute of Standards and Technology (NIST) database of retention data for non
      polar and polar stationary phases currently contains 292,924 data records for
      42,888 compounds. The database includes data for Kovats indices, linear indices,
      Lee indices, retention times and retention volumes. The first release of this
      database for non-polar stationary phases is available with NIST/US Environmental
      Protection Agency (EPA)/National Institutes of Health (NIH) Mass Spectral
      Database (June 2005) and through the internet (NIST Chemistry WebBook). The paper
      describes the database and the process by which it has been compiled. The format
      of data presentation and the quality control procedures are described. Data
      sources of gas chromatographic retention data are also discussed.

PMID- 17543316
TI  - Adsorption equilibrium of fructosyltransferase on a weak anion-exchange resin.
AB  - The adsorption equilibrium of a glycoprotein, fructosyltransferase from
      Aureobasidium pullulans, on an anion-exchange resin, Sepabeads FP-DA activated
      with 0.1M NaOH, was investigated. The adsorption isotherms were determined at 20
      degrees C in a phosphate-citrate buffer with pH 6.0 using the static method.
      Sodium chloride was used to adjust the ionic strength in the range from 0.0215 to
      0.1215 mol dm(-3) which provided conditions varying from a weak effect of salt
      concentration on protein binding to its strong suppression. The equilibrium data
      were very well fitted by means of the steric mass-action model when the ion
      exchange capacity of 290 mmol dm(-3) was obtained from independent frontal column
      experiments. The model fit provided the protein characteristic charge equal to
      1.9, equilibrium constant 0.326, and steric factor 1.095 x 10(5).

PMID- 17543317
TI  - Comparison between the efficiencies of columns packed with fully and partially
      porous C18-bonded silica materials.
AB  - The chromatographic performance of a new brand of shell particles is compared to
      that of a conventional brand of totally porous silica particles having a similar
      size. The new material (Halo, Advanced Materials Technology, Wilmington, DE) is
      made of 2.7 microm particles that consist in a 1.7 microm solid core covered with
      a 0.5 microm thick shell of porous silica. The other material consists of the
      porous particles of a conventional 3 microm commercial silica-B material. These
      two columns have the same dimensions, 150 mm x 4.6mm. The reduced plate heights
      of two low molecular weight compounds, naphthalene and anthracene, two peptides
      (lys-bradykinin and bradykinin), and four proteins, insulin, lysozyme, beta
      lactoglobulin, and bovine serum albumin were measured in a wide flow rate range
      and analyzed on the basis of the Van Deemter equation and of modern models for
      its terms. The Halo column provides a smaller axial diffusion coefficient B and a
      smaller eddy dispersion term A than the other column, a result consistent with
      its lower internal porosity (in(p)=0.19 versus 0.42) and with the narrower size
      distribution of its particles (sigma=5% versus 13%). The two columns have similar
      C terms for the two low molecular weight compounds and for the two peptides.
      However, the C term of the proteins that are not excluded is markedly lower on
      the column packed with the Halo particles than on the other column. A recent
      theoretical analysis of the mass transfer kinetics in shell particles predicts a
      C term for moderately retained proteins (3<k'<5) that is about 35% lower for
      shell than for fully porous particles while the experimental data show a value
      nearly 45% lower, an excellent agreement considering that the internal tortuosity
      of the particles might be different, affecting the ratio of the effective
      diffusivities (D(eff)) of the proteins in the two materials. Surprisingly, the
      Kozeny-Carman constant of the Halo packed column is 50% larger than that of the
      other column, in spite of which the permeability of the Halo column is slightly
      larger, due to its larger external porosity.

PMID- 17543318
TI  - Covalently linked DNA/protein multilayered film for controlled DNA release.
AB  - A stable, biocompatible single strand DNA (ssDNA)/bovine serum albumin (BSA)
      multilayered film for control release of DNA was fabricated on PEI-coated quartz
      slides, gold-evaporated plates and silicon wafers, respectively through a
      formaldehyde-induced, covalently linked layer-by-layer (LBL) assembly technique.
      The constructed film structure was well characterized by using UV-vis
      spectrometry, surface plasmon resonance (SPR) and atomic force microscopy (AFM).
      The results showed that the DNA incorporated LBL film was fabricated successfully
      and the amount of ssDNA and BSA in the film could be tailored simply by
      controlling the number of the bilayers. The control release of DNA from the film
      was also monitored in this study. UV-vis spectrometry, SPR and AFM measurements
      indicated that the release of ssDNA and amino acid was adjustable by changing the
      proteinase K incubation time. This biocompatible covalently assembled film
      demonstrates an innovative approach to engineer a DNA/protein based nanostructure
      for controlled DNA release, which could provide stability, controllability and
      flexibility superior to that of LBL film assembled by electrostatic attraction.
      Since the film in this work can be assembled on different substrates, it is very
      feasible to fabricate nanoparticle-based gene therapy systems with this new
      approach and to have great potential in biomedical applications.

PMID- 17543319
TI  - Adsorption of paraffin vapor on oxidized molybdenum substrates at nano- and micro
      scales.
AB  - Sputtered oxidized molybdenum surfaces were exposed at room temperature for
      different times to paraffin vapors obtained at 150 degrees C. Scanning
      polarization force microscopy (SPFM), optical and confocal microscopy were used
      to characterize the surfaces. The condensed morphologies are complex and strongly
      dependent upon the quantity of vapor molecules deposited on the substrate
      surface. A thin paraffin film is initially formed and quite uniform nano-height
      drops are nucleated randomly over it within 10-20 s time exposures. Their average
      contact angle ranged between 1 degrees -2.5 degrees . Further vapor deposition
      led to a more complex regime where nano-height drops do not show a clear
      interface with the film, while micro-sized drops do. The tangent approximation
      method adopted by Salmeron and Xu for the nano-drop regimes was extended to the
      micro-sized drop regime obtaining an averaged effective contact angle equal to 4
      degrees -5 degrees . Both nano-height and micro-sized drops shape and effective
      contact angles have been discussed taking into account their interactions between
      the film and the drops.

PMID- 17543320
TI  - Surface characterization of adsorbents in ultrasound-assisted oxidative
      desulfurization process of fossil fuels.
AB  - Surface properties of two different phases of alumina were studied through SEM
      images. Characterization of amorphous acidic alumina and crystalline boehmite by
      XRD explains the differences in adsorption capacities of each sample. Data from
      small angle neutron scattering (SANS) provide further results regarding the
      ordering in amorphous and crystalline samples of alumina. Quantitative
      measurements from SANS are used for pore size calculations. Higher disorder
      provides more topological traps, irregularities, and hidden grooves for higher
      adsorption capacity. An isotherm model was derived for adsorption of
      dibenzothiophene sulfone (DBTO) by amorphous acidic alumina to predict and
      calculate the adsorption of sulfur compounds. The Langmuir-Freundlich model
      covers a wide range of sulfur concentrations. Experiments prove that amorphous
      acidic alumina is the adsorbent of choice for selective adsorption in the
      ultrasound-assisted oxidative desulfurization (UAOD) process to produce ultra-low
      sulfur fuel (ULSF).

PMID- 17543321
TI  - The calcite/water interface I. Surface charge in indifferent electrolyte media
      and the influence of low-molecular-weight polyelectrolyte.
AB  - Suspensions of calcium carbonate in water with an indifferent background
      electrolyte (NaCl) have been investigated using several techniques. Particular
      attention was paid to the dissolution of calcite at equilibrium and as a function
      of sodium polyacrylate (NaPA) concentration. Also of interest was how this
      affects the magnitude of the surface charge and the zeta potential. The
      development of the interfacial charge is discussed with respect to the dissolved
      species and with regard to the kinetics of dissolution. The partial pressure of
      CO(2) in solution is believed to play a major role in determining the sign of the
      charge at equilibrium. In addition to effectively stabilizing calcite
      suspensions, NaPA was also found to act as a chelating agent at the calcite
      surface, enhancing the dissolution. The order of addition of NaPA to the
      suspensions was found to be important.

PMID- 17543322
TI  - Competitive adsorption of malachite green and Pb ions on natural zeolite.
AB  - A natural zeolite was employed as adsorbent for removal of malachite green and
      Pb(2+) ions from aqueous solution. A batch system was applied to study the
      adsorption behaviour of the dye and heavy metal in single and binary systems on
      the natural zeolite. Kinetic studies indicate that malachite green and Pb(2+)
      adsorption on the natural zeolite in a single component system follows the first
      order kinetics and the adsorption is diffusion process with single-stage for
      Pb(2+) and two-stage for malachite green. For the single system, malachite green
      adsorption isotherm follows the Langmuir model while Pb adsorption follows the
      Freundlich isotherm. The adsorption capacities of malachite green and Pb at 30
      degrees C, pH 6 are 5x10(-5) and 10x10(-5)mol/g, respectively. In the binary
      system, malachite green and Pb(2+) exhibit competitive adsorption on the natural
      zeolite. The adsorption is reduced to 90 and 80% of single component of Pb(2+)
      and malachite green, respectively. However, the total adsorption is higher. In
      the binary system, Pb(2+) exhibits relative higher affinity and selectivity to be
      adsorbed on zeolite. The dynamic adsorption of malachite green and Pb(2+) still
      follows the first-order kinetics.

PMID- 17543323
TI  - Catalytic effects on methanol oxidation produced by cathodization of platinum
      electrodes.
AB  - A catalytic effect is found for methanol oxidation after new active surface
      states are produced on polycrystalline platinum by potentiostatic cathodization
      in acid media at room temperature. This procedure originates surface states not
      available on the original polycrystalline electrodes with unexpected cyclic
      voltammetric responses; i.e., at least four new peaks below 0.9 V are observed.
      The cathodization process also induces a rearrangement of the bulk platinum
      oxide, showing a defined peak at 1.2 V. The appearance of these new states is
      also proven by open-circuit potential decays. The electrocatalytic activity of
      these new surfaces in methanol oxidation is compared with that of the untreated
      electrodes by electrochemical impedance spectroscopy, chronoamperometry, and
      cyclic voltammetry. The cathodic procedure enhances the methanol oxidation
      voltammetric current peaks with charge density values higher than those on
      untreated platinum. The integration of chronoamperometric plots over 10 min in
      methanol acid media presents the largest difference between 0.6 and 0.7 V with
      respect to the original surface. Analysis of the impedance data shows that the
      values of polarization resistance for methanol oxidation on the cathodically
      treated platinum are lower than those of the original surface. According to the
      time constant values for methanol oxidation, the original surface can be
      considered less tolerant of the formation of catalytic poisons. A discussion of
      the most likely mechanism for the formation of the new active sites on platinum
      is presented here, assuming the presence of hydrogen subsurface states, ordered
      water clusters, and low-coordinated platinum atoms.

PMID- 17543324
TI  - Hierarchically structured superhydrophilic coatings fabricated by self-assembling
      raspberry-like silica nanospheres.
AB  - Raspberry-like silica nanospheres were prepared by electrostatic self-assembly of
      polyelectrolytes and monodisperse silica nanoparticles of two different sizes,
      and their coatings were fabricated via layer-by-layer assembly with
      polyelectrolytes and following calcination. The morphology of the raspberry-like
      silica nanospheres and their coatings were observed by scanning and transmission
      electron microscopies. The surface properties of these coatings were investigated
      by measuring their water contact angles, and the results showed that such
      hierarchically structured coatings had unique superhydrophilic and antifogging
      properties. Finally, the formation mechanism and the property-structure
      relationship were discussed in details.

PMID- 17543325
TI  - Immunocytological detection of lymph node metastases in dogs with malignant
      epithelial tumours.
AB  - The aim of this study was to compare immunolabelling of cytological specimens
      with conventional staining in the detection of metastases in lymph nodes from
      dogs with carcinoma. Cytological touch imprints of 161 lymph nodes from 72 dogs,
      as well as 50 fine needle aspirates from 23 dogs, with malignant epithelial
      tumours were included in the study. Immunolabelling was performed with
      commercially available human antibodies. Touch imprints of all lymph nodes were
      labelled with broad spectrum anticytokeratins AE1/AE3 and KL1. In addition, lymph
      node touch imprints from dogs with primary tumours that reacted positively with
      the specific anticytokeratins CK7 (n=104) and CK20 (n=20) were also labelled with
      CK7 and CK20. Fine needle aspirates of 50 lymph nodes were examined by
      immunolabelling with AE1/AE3. "Reference investigations" with a combination of
      histological and immunohistochemical methods were performed on all lymph nodes.
      The immunocytological detection of lymph node metastases with the broad spectrum
      anti-cytokeratin AE1/AE3 in imprint smears resulted in a significant increase in
      sensitivity (0.99 vs 0.88 [conventional stain]) and in negative predictive value
      (0.99 vs 0.85) (P<0.01; t-test). Micrometastases in particular were detected more
      readily. Specificity (0.93 vs 0.88) and positive predictive value (0.95 vs 0.90)
      did not differ significantly between the two techniques. Immunolabelling with KL1
      was associated with lower sensitivity and negative predictive value, indicating
      lack of cross-reactivity of this antibody with canine epithelial cells. In fine
      needle aspirates the detection of lymph node metastases, especially
      micrometastases, was more efficient by mean of immunolabelling with AE1/AE3 than
      by conventional staining. The study indicated the value of immunocytological
      labelling for the detection of metastases in cytological specimens of canine
      lymph node preparations.

PMID- 17543326
TI  - A proposal for a T-wave alternans index.

PMID- 17543327
TI  - A case of acute myocardial infarction due to indirect lightning strike.
AB  - Lightning strike is a natural phenomenon with potentially devastating effects and
      represents one of the leading causes of cardiac arrest and death from
      environmental phenomena. Almost every organ system may be impaired as lightning
      passes through the human body preferring the pathways that the lowest resistance
      between the contact points. Lightning can also have widespread effects on the
      cardiovascular system, producing extensive catecholamine release or autonomic
      stimulation. The victim may develop hypertension, tachycardia, nonspecific
      electrocardiographic changes (including prolongation of the QT interval and
      transient T-wave inversion), and myocardial necrosis with release of creatine
      phosphokinase-MB fraction. We present the case of a 13-year-old boy with acute
      myocardial infarction secondary to an indirect lightning strike.

PMID- 17543328
TI  - Short-term memory for time in children and adults: A behavioral study and a
      model.
AB  - This experiment investigated the effect of the short-term retention of duration
      on temporal discrimination in 5- and 8-year-olds, as well as in adults, by using
      an episodic temporal generalization task. In each age group, the participants'
      task was to compare two successive durations (a standard and a comparison
      duration) separated by a retention interval of 500ms, 5s, or 10s, with the order
      of presentation of these two durations being counterbalanced. The results
      revealed a shortening effect for the first presented stimulus in all of the age
      groups, although this was greater in the younger children, thereby indicating the
      presence of a negative time-order error. Furthermore, introducing a retention
      delay between the two durations did not produce a shortening effect but instead
      flattened the generalization gradient, especially in the younger children.
      However, this flattening of the generalization gradient with the retention delay
      was more marked between 500ms and 5s than between 5s and 10s. Thus, retaining the
      first duration in short-term memory during a task requiring the comparison of two
      successive durations reduced temporal discrimination accuracy and did so to a
      greater extent in the younger children.

PMID- 17543329
TI  - Mechanisms to reduce dehydration stress in larvae of the Antarctic midge, Belgica
      antarctica.
AB  - The Antarctic midge, Belgica antarctica, is exposed to frequent periods of
      dehydration during its prolonged larval development in the cold and dry Antarctic
      environment. In this study, we determined the water requirements of the larvae
      and the mechanisms it exploits to reduce the stress of drying. Larvae lost water
      at an exceptionally high rate (>10%/h) and tolerated losing a high portion (>70%)
      of their water content. Larvae were unable to absorb water from subsaturated
      water vapor (< or = 0.98 a(v)) to replenish their water stores, thus this midge
      relies exclusively on the intake of liquid water to increase its pool of body
      water and maintain water balance. To reduce dehydration stress, the midge
      employed a variety of mechanisms. Behaviorally, the larvae suppressed water loss
      by clustering. In response to slow dehydration, glycerol concentration increased
      2-fold and trehalose concentration increased 3-fold, responses that are known to
      decrease the rate of water loss and increase dehydration tolerance. No changes in
      the mass of cuticular lipids occurred in response to desiccation, but the
      observed shift to longer hydrocarbons likely contributes to reduced water loss as
      the larvae dehydrate. As the larvae dehydrated, their oxygen consumption rate
      dropped, resulting in a reduction of water loss by respiration. Lastly, one bout
      of slow dehydration also enhanced the larva's ability to survive subsequent
      dehydration, suggesting that the larvae have the capacity for drought
      acclimation. Thus, these hydrophilic midge larvae prevent dehydration by multiple
      mechanisms that collectively reduce the water loss rate and increase dehydration
      tolerance.

PMID- 17543330
TI  - Effects of diapause and cold-acclimation on the avoidance of freezing injury in
      fat body tissue of the rice stem borer, Chilo suppressalis Walker.
AB  - Overwintering freeze-tolerant larvae of Chilo suppressalis can survive at -25
      degrees C, but non-diapausing larvae cannot. We reported earlier that to prevent
      intracellular freezing, which causes death in overwintering larvae of the Saigoku
      ecotype distributed in southwestern Japan, water leaves and glycerol enters fat
      body cells through water channels during freezing. However, it is still unclear
      how diapause and low-temperature exposure are related to the acquisition of
      freeze tolerance. We compared the extent of tissue damage, accumulation of
      glycerol, and transport of glycerol and water in fat body tissues between cold
      acclimated and non-acclimated non-diapausing and diapausing larvae. The tissue
      from cold-acclimated diapausing larvae could survive only when frozen in Grace's
      insect medium with 0.25 M glycerol at -20 degrees C. The protection provided by
      glycerol was offset by mercuric chloride, which is a water-channel inhibitor. Fat
      body tissue isolated from non-acclimated diapausing larvae was injured by
      freezing even though glycerol was added to the medium, but the level of freezing
      injury was significantly lower than in non-diapausing larvae. Radiotracer assays
      in cold-acclimated diapausing larvae showed that during freezing, water left the
      cells into the medium and glycerol entered the cells from the medium at the same
      time. Therefore, in Saigoku ecotype larvae of the rice stem borer, both diapause
      and cold-acclimation are essential to accumulate glycerol and activate aquaporin
      for the avoidance of freezing injury.

PMID- 17543331
TI  - Modulation of rate by autonomic agonists in SAN cells involves changes in
      diastolic depolarization and the pacemaker current.
AB  - Two distinct intracellular mechanisms have been proposed to affect the firing
      rate of cardiac pacemaker cells: one involves modulation of the I(f) current by
      the second messenger cAMP, and one relies upon disruption or alteration of SR
      Ca2+ transients during activity. Although both mechanisms are necessary for
      proper automaticity and autonomic rate control, the specific contribution of each
      to pacemaking is still debated. We investigated if the two processes can be
      separated based on potentially different effects on action potential
      characteristics during rate modulation. To identify specific I(f)-mediated
      effects, we used the selective I(f) blocker ivabradine and found that ivabradine
      (3 microM) slows rate (-16.2%) by selectively reducing (-31.9%) the steepness of
      early diastolic depolarization (EDD). On the other hand ryanodine (3 microM),
      used to evaluate the effects of abolishment of SR Ca2+ transients, slowed rate (
      31.3%) by depolarizing the take-off potential (TOP, 18.1%) without affecting EDD.
      We therefore used these two parameters to identify I(f)-based or SR Ca2+
      transients-based processes and analyzed the effects on action potential's
      characteristics of Rp-cAMPs (50 microM), a membrane permeable cAMP analogue
      directly activating f-channels; we found that Rp-cAMPs accelerates rate by
      increasing EDD (+42.3%) without modifying TOP. Finally, rate modulation was
      achieved by muscarinic (ACh 0.01 microM) or beta-adrenergic (Iso 1 microM)
      stimulation; in both cases, rate changes were associated with modifications of
      EDD (ACh, -29.3% and Iso, +47.6%) and not of TOP. We conclude that rate-related
      changes in the EDD induced by autonomic agonists are mediated by I(f) and not by
      processes involving SR Ca2+ transients.

PMID- 17543332
TI  - Processing of proteins by the molecular chaperone Hsp104.
AB  - The molecular chaperone Hsp104 is an AAA+ ATPase (ATPase associated with a
      variety of cellular activities) from yeast that catalyzes protein disaggregation.
      Using mutagenesis, we impaired nucleotide binding or hydrolysis in the two
      nucleotide-binding domains (NBD) of Hsp104 and analyzed the consequences for
      chaperone function by monitoring ATP hydrolysis, polypeptide binding, polypeptide
      processing, and disaggregation. Our results reveal that ATP binding to NBD1
      serves as a central regulatory switch for the chaperone; it triggers binding of
      polypeptides, and stimulates ATP hydrolysis in the C-terminal NBD2 by more than
      two orders of magnitude, implying that ATP hydrolysis in this domain is important
      for disaggregation. Moreover, we show that Hsp104 actively unfolds its
      polypeptide substrates during processing, demonstrating that AAA+ proteins
      involved in disaggregation share a common threading mechanism with AAA+ proteins
      mediating protein unfolding/degradation.

PMID- 17543333
TI  - Role of N and C-terminal tails in DNA binding and assembly in Dps: structural
      studies of Mycobacterium smegmatis Dps deletion mutants.
AB  - Mycobacterium smegmatis Dps degrades spontaneously into a species in which 16 C
      terminal residues are cleaved away. A second species, in which all 26 residues
      constituting the tail were deleted, was cloned, expressed and purified. The first
      did not bind DNA but formed dodecamers like the native protein, while the second
      did not bind to DNA and failed to assemble into dodecamers, indicating a role in
      assembly also for the tail. In the crystal structure of the species without the
      entire C-terminal tail the molecule has an unusual open decameric structure
      resulting from the removal of two adjacent subunits from the original dodecameric
      structure of the native form. A Dps dodecamer could assemble with a dimer or one
      of two trimers (trimer-A and trimer-B) as intermediate. Trimer-A is the
      intermediate species in the M. smegmatis protein. Estimation of the surface area
      buried on trimerization indicates that association within trimer-B is weak. It
      weakens further when the C-terminal tail is removed, leading to the disruption of
      the dodecameric structure. Thus, the C-terminal tail has a dual role, one in DNA
      binding and the other in the assembly of the dodecamer. M. smegmatis Dps also has
      a short N-terminal tail. A species with nine N-terminal residues deleted formed
      trimers but not dodecamers in solution, unlike wild-type M. smegmatis Dps, under
      the same conditions. Unlike in solution, the N-terminal mutant forms dodecamers
      in the crystal. In native Dps, the N-terminal stretch of one subunit and the C
      terminal stretch of a neighboring subunit lock each other into ordered positions.
      The deletion of one stretch results in the disorder of the other. This disorder
      appears to result in the formation of a trimeric species of the N-terminal
      deletion mutant contrary to the indication provided by the native structure. The
      ferroxidation site is intact in the mutants.

PMID- 17543334
TI  - Structural characterization of the tetrameric form of the major cat allergen Fel
      d 1.
AB  - Felis domesticus allergen 1(Fel d 1) is a 35 kDa tetrameric glycoprotein formed
      by two heterodimers which elicits IgE responses in 95% of patients with allergy
      to cat. We have previously established in vitro conditions for the appropriate
      folding of recombinant Fel d 1 using a direct linkage of chain 1 to chain 2
      (construct Fel d 1 (1+2)) and chain 2 to chain 1 (construct Fel d 1 (2+1)).
      Although the crystal structure of Fel d 1 (2+1) revealed a striking structural
      similarity to that of uteroglobin, a steroid-inducible cytokine-like molecule
      with anti-inflammatory and immunomodulatory properties, no functional tetrameric
      form of Fel d 1 could be identified. Here we present the crystal structure of the
      Fel d 1 (1+2) tetramer at 1.6 A resolution. Interestingly, the crystal structure
      of tetrameric Fel d 1 reveals two different calcium-binding sites. Symmetrically
      positioned on each side of the Fel d 1 tetramer, the external Ca(2+)-binding
      sites correspond to a putative Ca(2+)-binding site previously suggested for
      uteroglobin. The second Ca(2+)-binding site lies within the dimerization
      interface, stabilizing the formation of the Fel d 1 tetramer, and inducing
      important local conformational changes that directly govern the shape of two
      water-filled cavities. The crystal structure suggests a potential portal for an
      unknown ligand. Alternatively, the two cavities could be used by the allergen as
      a conditional inner space allowing for the spatial rearrangement of centrally
      localized side-chains, such as Asp130, without altering the overall fold of the
      molecule. The striking structural similarity of the major cat allergen to
      uteroglobin, coupled to the identification in the present study of a common
      Ca(2+)-binding site, let us speculate that Fel d 1 could provoke an allergic
      response through the modulation of phospholipase A2, by sequestering Ca ions in a
      similar manner as previously suggested for uteroglobin.

PMID- 17543335
TI  - Structure of a complex of human lactoferrin N-lobe with pneumococcal surface
      protein a provides insight into microbial defense mechanism.
AB  - Human lactoferrin, a component of the innate immune system, kills a wide variety
      of microorganisms including the Gram positive bacteria Streptococcus pneumoniae.
      Pneumococcal surface protein A (PspA) efficiently inhibits this bactericidal
      action. The crystal structure of a complex of the lactoferrin-binding domain of
      PspA with the N-lobe of human lactoferrin reveals direct and specific
      interactions between the negatively charged surface of PspA helices and the
      highly cationic lactoferricin moiety of lactoferrin. Binding of PspA blocks
      surface accessibility of this bactericidal peptide preventing it from penetrating
      the bacterial membrane. Results of site-directed mutagenesis, in vitro protein
      binding assays and isothermal titration calorimetry measurements corroborate that
      the specific electrostatic interactions observed in the crystal structure
      represent major associations between PspA and lactoferrin. The structure provides
      a snapshot of the protective mechanism utilized by pathogens against the host's
      first line of defense. PspA represents a major virulence factor and a promising
      vaccine candidate. Insights from the structure of the complex have implications
      for designing therapeutic strategies for treatment and prevention of pneumococcal
      diseases that remain a major public health problem worldwide.

PMID- 17543336
TI  - c-Abl-binding protein interacts with p21-activated kinase 2 (PAK-2) to regulate
      PDGF-induced membrane ruffles.
AB  - p21-Activated kinases (PAKs) are serine/threonine kinases involved in multiple
      cellular functions including cytoskeleton regulation, proliferation and
      apoptosis. We performed a screen for proteins interacting with PAK-2, a
      ubiquitously expressed kinase involved in apoptotic signaling. Among the PAK-2
      interacting proteins were different members of the Abl-binding protein family.
      Abl-binding proteins bound to a proline-rich region of PAK-2 located in the
      regulatory N terminus. Moreover, active PAK-2 phosphorylated Abl-binding proteins
      in vitro. Interestingly, we show that PAK-2 also interacted with c-Abl but via a
      different domain than with the Abl-binding proteins. PAK-2 and Abi-1 co-localized
      in the cytoplasm and to membrane dorsal ruffles induced by PDGF treatment.
      Expression of mutant PAK-2 deficient in binding to Abl-binding proteins or
      silencing of PAK-2 expression prevented the formation of membrane dorsal ruffles
      in response to PDGF. Our findings define a new class of PAK-interacting proteins,
      which play an important role in actin cytoskeletal reorganization.

PMID- 17543337
TI  - Non-homologous recombination of deoxyribonucleoside kinases from human and
      Drosophila melanogaster yields human-like enzymes with novel activities.
AB  - In antiviral and cancer therapy, deoxyribonucleoside kinases (dNKs) are often the
      rate-limiting step in activating nucleoside analog (NA) prodrugs into their
      cytotoxic, phosphorylated forms. We have constructed libraries of hybrid enzymes
      by non-homologous recombination of the pyrimidine-specific human thymidine kinase
      2 and the broad-specificity dNK from Drosophila melanogaster; their low sequence
      identity has precluded engineering by conventional, homology-dependent shuffling
      techniques. From these libraries, we identified chimeras that phosphorylate
      nucleoside analogs with higher activity than either parental enzyme, and that
      possess new activity towards the anti-HIV prodrug 2',3'-didehydro-3'
      deoxythymidine (d4T). These results demonstrate the potential of non-homologous
      recombination within the dNK family for creating enzymes with new and improved
      activities towards nucleoside analogs. In addition, our results exposed a
      previously unknown role for the C-terminal regions of these dNKs in determining
      substrate selectivity.

PMID- 17543338
TI  - Norepinephrine in small-for-size liver grafts: an experimental study in pigs.
AB  - BACKGROUND: Norepinephrine plasma levels may play a role in small-for-size grafts
      dysfunction at the early posttransplant period. MATERIALS AND METHODS: The 18
      pigs used as recipients were assigned to group 1 (n = 6), group 2 (n = 6), and
      group 3 (n = 6) and given grafts with graft-to-recipient volume ratios of 1:1,
      2:3, and 1:3, respectively. Blood serum norepinephrine was measured by high
      performance liquid chromatography with electrochemical detection at the following
      time points: pre-anhepatic period (baseline); anhepatic period; and 30, 60, 180,
      and 360 min after reperfusion. Graft arterial and portal vein flows were obtained
      30, 60, 180, and 360 min after reperfusion by the aid of an ultrasonic flowmeter.
      Aspartate transferase (AST) and international normalized ratio (INR) were
      measured before the procedure (baseline), and at 180 and 360 min after
      reperfusion. RESULTS: Anhepatic phase was characterized by a significant increase
      (6- to 8-fold) of norepinephrine in all groups (P < 0.05). In groups 1 and 2
      plasma norepinephrine returned to normal values 30 min after reperfusion. In
      group 3, plasma norepinephrine remained significantly increased at every time
      point of the study compared to groups 1 and 2 (P < 0.001). Hepatic artery and
      portal vein flows in group 3 were significantly (P < 0.05) reduced and increased,
      respectively, compared to groups 1 and 2 at all times measured. Liver function
      tests (AST and INR) 360 min after reperfusion were significantly higher in group
      3 compared to groups 1 and 2. CONCLUSIONS: Norepinephrine levels are increased in
      very small-for-size grafts and this increase may be associated with early graft
      dysfunction.

PMID- 17543339
TI  - Surgical site infections in plastic surgery: an italian multicenter study.
AB  - BACKGROUND: Plastic surgery interventions have increased in terms of frequency,
      complexity of surgical procedures, and postoperative complications, particularly
      surgical site infections (SSIs). The aim of the present study was to assess the
      SSI frequency in plastic and reconstructive surgery settings in Italy and to
      evaluate the associated risk factors. METHODS: From June 2004 to June 2005, a
      prospective multicenter study including 2806 consecutive patients was conducted
      in 23 Italian plastic and reconstructive units. To assess potential risk factors
      for surgical site infection, a conditional logistic regression model was used and
      results were exposed in terms of odds ratio (OR) with their respective 95%
      confidence interval (CI). RESULTS: SSIs occurred in 85/2806 (3%) patients. Sixty
      (70.6%), 24 (28.2%), and 1 (1.2%) SSIs were classified as superficial, deep, and
      organ/space, respectively. Sixty-six percent of the SSIs were diagnosed during
      postdischarge surveillance. At multivariate analysis, diabetes mellitus, chronic
      obstructive pulmonary disease, preoperative radiotherapy, and use of surgical
      drains were significantly associated with the occurrence of SSI. CONCLUSIONS: Our
      findings, based on a large population including all types of plastic and
      reconstructive interventions, provided consistent information on potential risk
      factors for SSI in this surgical setting. Moreover, the high rate of SSI found
      during the postdischarge surveillance underlines the need for improving active
      surveillance methodologies in this surgical setting.

PMID- 17543340
TI  - Prognostic values of matrix metalloproteinase family expression in human
      colorectal carcinoma.
AB  - BACKGROUND: We examined expression patterns of matrix metalloproteinase (MMP),
      tissue inhibitor of metalloproteinase (TIMP), and reversion-inducing cysteine
      rich protein with Kazal motifs (RECK) in colorectal cancer tissues to assess
      their prognostic significance. MATERIALS AND METHODS: mRNA expressions of 17
      MMPs, 4 TIMPs, and RECK were measured in 112 colorectal cancerous tissues, 20
      normal mucosa tissues, and 11 metastatic liver lesions by real-time reverse
      transcriptional-polymerase chain reaction. The protein level expressions were
      confirmed with immunohistochemistry. RESULTS: Cancers and normal mucosa displayed
      highly significant differences (P < 0.01) in expression of nine genes (MMP-1, -3,
      -7, -9, -10, -11, -12, -14, and RECK). Primary cancers and metastatic lesions
      showed highly significant differences (P < 0.01) in MMP-1, -10, -11, and TIMP-1.
      MMP-12 expression was higher in the primary tumors that were associated without
      hepatic metastasis than those with metastasis (P < 0.01). High expression of MMP
      15 was related to longer disease-free survival (generalized Wilcoxon test, P <
      0.0062; Cox hazard model, P < 0.028, hazard ratio, 0.099). CONCLUSIONS: MMP,
      TIMP, RECK expression patterns may provide an insight into extracellular matrix
      degrading (which is characteristic of colorectal cancers) and its role in
      metastasis.

PMID- 17543341
TI  - Is there a need for a continuous local pain therapy, a peridural catheter, or an
      opioid-based patient controlled analgesia pump after radical axillary lymph node
      dissection?

PMID- 17543342
TI  - The effect of immunosuppression on peritoneal adhesions formation after small
      bowel transplantation in rats.
AB  - BACKGROUND: The reported incidence of adhesion related small bowel obstruction
      after abdominal organ transplantation is considerably lower than other abdominal
      procedures. The purpose of the study was to investigate the influence of
      immunosuppression on peritoneal adhesion formation after intestinal
      transplantation in rats. METHODS: Four groups of rats (n = 6) underwent small
      bowel intestinal transplantation in syngeneic (Groups A, B) and allogeneic
      (Groups C, D) combinations. Groups B and D received tacrolimus immunosuppression
      1 mg/kg/d. Animals were euthanized on postoperative day 7, and the total adhesion
      score (TAS), tissue hydroxyproline content (HPC), TGF-beta mRNA expression levels
      and histology were examined. RESULTS: All of the animals in Group C showed severe
      histological (Grade III) acute cellular rejection. There were no histological
      signs of rejection in Group D. A significant reduction in TAS was observed in
      tacrolimus treated animals in both syngeneic and allogeneic combinations (Groups
      B and D), compared with controls (Groups A and C) (P < 0.001 and P < 0.01,
      respectively). TAS results correlated with the differences in TGF-beta levels
      that showed significant reduction when each immunosuppressed group was compared
      with its nontreated counterpart, i.e., (Groups B versus A, P < 0.05, and Groups D
      versus C, P < 0.01). TGF-beta levels were significantly high in the rejection
      group (C) and correlated with the intense adhesion formation that was
      demonstrated in that group. Group C was also the only group in which a
      significant elevation in HPC was demonstrated (P < 0.001). CONCLUSION: Intense
      adhesion formation occurs during early posttransplant acute rejection.
      Postsurgical adhesion formation is significantly reduced in immunosuppressed rats
      after intestinal transplantation.

PMID- 17543344
TI  - Relation between complexity and stability in food webs with adaptive behavior.
AB  - We investigate the influence of functional responses (Lotka-Volterra or Holling
      type), initial topological web structure (randomly connected or niche model),
      adaptive behavior (adaptive foraging and predator avoidance) and the type of
      constraints on the adaptive behavior (linear or nonlinear) on the stability and
      structure of food webs. Two kinds of stability are considered: one is the network
      robustness (i.e., the proportion of species surviving after population dynamics)
      and the other is the species deletion stability. When evaluating the network
      structure, we consider link density as well as the trophic level structure. We
      show that the types of functional responses and initial web structure do not have
      a large effect on the stability of food webs, but foraging behavior has a large
      stabilizing effect. It leads to a positive complexity-stability relationship
      whenever higher "complexity" implies more potential prey per species. The other
      type of adaptive behavior, predator avoidance behavior, makes food webs only
      slightly more stable. The observed link density after population dynamics depends
      strongly on the presence or absence of adaptive foraging, and on the type of
      constraints used. We also show that the trophic level structure is preserved
      under population dynamics with adaptive foraging.

PMID- 17543343
TI  - Detection and characterization of hepatic engraftment of embryonic stem derived
      cells by fluorescent stereomicroscopy.
AB  - BACKGROUND: Embryonic stem (ES) cells have been investigated as a potential
      replacement therapy for failed organs, such as the liver. However, detection of
      hepatic engraftment from candidate stem cells has been difficult due to low
      engraftment efficiency. Previous detection methods required that the graft be
      processed by molecular and/or immunohistochemical techniques, limiting further
      functional studies. This study evaluated the use of three-dimensional fluorescent
      stereomicroscopy for gross detection of ES cell derived hepatic engraftment.
      MATERIAL AND METHODS: Murine ES cells expressing the enhanced green fluorescence
      protein (EGFP) underwent directed endodermal lineage differentiation. Three days
      after two thirds partial hepatectomy, cells were injected into the liver
      parenchyma, and livers were harvested at 10 to 20 d and examined by fluorescence
      stereomicroscopy with a GFP2 long pass filter (100447084; Leica Microsystems AG,
      Wetzlar, Germany). The sensitivity and reliability of the test was evaluated
      using quantitative polymerase chain reaction (q-PCR) to assay for the presence of
      EGFP mRNA in the tissue. RESULTS: Fluorescent microscopy detected EGFP-positive
      cells engrafted with normal histology in 5 of 11 specimens. EGFP mRNA was
      confirmed in all five specimens by q-PCR. Only one of the 11 specimens was
      negative by fluorescence stereomicroscopy and positive by q-PCR, P < 0.02,
      Fisher's exact test. CONCLUSION: Utilization of three-dimensional
      stereomicroscopy with a GFP2 long pass filter is a powerful and fast screening
      tool for GFP-ES derived hepatic engraftment.

PMID- 17543345
TI  - Cancer immunotherapy, mathematical modeling and optimal control.
AB  - Clinical immunologists, among other problems, routinely face a question: what is
      the best time and dose for a certain therapeutic agent to be administered to the
      patient in order to decrease/eradicate the pathological condition? In cancer
      immunotherapies the therapeutic agent is something able to elicit an immune
      response against cancer. The immune response has its own dynamics that depends on
      the immunogenicity of the therapeutic agent and on the duration of the immune
      response. The question then is "how can we decide when and how much of the drug
      to inject so to have a prolonged and effective immune response to the cancer?".
      This question can be addressed in mathematical terms in two stages: first one
      construct a mathematical model describing the cancer-immune interaction and
      secondly one applies the theory of optimal control to determine when and to which
      extent to stimulate the immune system by means of an immunotherapeutic agent
      administered in discrete variable doses within the therapeutic period. The
      solution of this mathematical problem is described and discussed in this article.
      We show that the method employed can be applied to find the optimal protocol in a
      variety of clinical problems where the kinetics of the drug or treatment and its
      influence on the physiologic/pathologic functions have been described by a system
      of ordinary differential equations.

PMID- 17543346
TI  - The effects of insulin on glucose and fluid transport in the isolated small
      intestine of normal rats.
AB  - Chronically administered insulin returns enhanced maximal glucose transport
      capacity induced by diabetes to its normal state. In this study, the direct and
      acute effects of insulin on glucose transport in different parts of isolated
      small intestine were investigated. Mucosal Fluid Transport (MFT), Mucosal Glucose
      Transport (MGT) and Serosal Glucose Transport (SGT) were measured in the presence
      and absence of insulin in averted sacs, prepared from female Wistar rats. This
      study shows that the presence of insulin in vitro (40 and 80 microU/mL) can
      reduce MGT and SGT in different segments of the small intestine (duodenum,
      jejunum and ileum) after 30 min whereas it had no effect on MFT. Mucosal glucose
      transfer rates in the duodenum, jejunum and ileum of the controls were 6.07+/
      0.4, 6.34+/-0.62 and 6.43+/-0.47 mg/g tissue respectively which were
      significantly reduced to 3.82+/-0.93, 3.60+/-0.50 and 1.17+/-0.45 in the presence
      of 80 microU/mL of insulin. Serosal glucose transfer too was decreased
      significantly from 0.3+/-0.05, 0.57+/-0.07 and 0.43+/-.07 in the duodenum,
      jejunum and ileum to 0.16+/-0.03, 0.16+/-0.04 and .07+/-.02 respectively. Mucosal
      fluid transfer was not affected by insulin. Insulin was as effective whether it
      was added on the mucosal or the serosal side. The results of this study show that
      insulin can directly affect glucose transport in the small intestine; its
      physiological role must be examined. Direct effect of insulin deficiency on
      glucose absorption in diabetic patients may play a role in the pathophysiology of
      the disease.

PMID- 17543347
TI  - Effect of pre-treatment with St John's Wort on nephrotoxicity of cisplatin in
      rats.
AB  - An herbal health care supplement, St John's Wort (SJW, Hypericum perforatum) has
      become widely used in the treatment of depression, and is known to interact with
      therapeutic drugs. Here we report a preventive effect of SJW on cisplatin
      nephrotoxicity in rats. Rats were given SJW (400 mg/kg/day, p.o.) for 10
      consecutive days, and were injected with cisplatin (5 mg/kg, i.v.) on the day
      after the final SJW treatment. Cisplatin treatment increased the serum creatinine
      level, which is an index of nephrotoxicity, to 1.51+/-0.22 mg/dl (mean+/-SE) from
      0.28+/-0.05 mg/dl (control) on day 5 after the cisplatin injection. This increase
      fell significantly to 0.86+/-0.13 mg/dl by pre-treatment with SJW. Cisplatin
      induced histological abnormality of the kidney was blocked by pre-treatment with
      SJW. When SJW was administered for 10 days, the amounts of renal metallothionein
      (MT) and hepatic multidrug resistance protein 2 (Mrp2) were increased to 164.8+/
      13.0% and 220.8+/-39.3% (mean+/-SE) of controls, respectively. GSH levels in the
      kidney and liver were not changed. Total and free cisplatin concentration in
      serum was not influenced by SJW treatment. In conclusion, the results suggest
      that pre-treatment with SJW may diminish cisplatin nephrotoxicity.

PMID- 17543349
TI  - Methylmercury bioconcentration in muscle tissue of the European eel (Anguilla
      anguilla) from the Adour estuary (Bay of Biscay, France).

PMID- 17543350
TI  - [Benign sacrococcygeal teratoma in an adult].
AB  - Sacrococcygeal teratomas are rare congenital tumors generally discovered at
      birth. Exceptionally these tumors are observed in adults. Radical resection must
      be performed to avoid potentially malignant recurrence even if the primary lesion
      was benign. We report a case of a benign sacroccygeal teratoma diagnosed in a 25
      year-old male and discuss clinical features, pathological considerations and
      treatment.

PMID- 17543351
TI  - Involvement of nitric oxide in the inhibition of bone cancer-induced hyperalgesia
      through the activation of peripheral opioid receptors in mice.
AB  - Experiments were designed to elucidate the involvement of nitric oxide (NO) in
      the antihyperalgesic effect induced by the activation of peripheral mu-opioid
      receptors on osteosarcoma-induced thermal hyperalgesia in mice. Since this
      pathway has previously been shown to be involved in the antihyperalgesic effect
      induced by some drugs--including opiates--on inflammatory pain, experiments were
      also performed in inflamed mice. The intraplantar administration of loperamide
      (15 microg) abolishes the thermal hyperalgesia that appears 4 weeks after the
      intratibial inoculation of NCTC 2472 cells in C3H/HeJ mice. The blockade of this
      effect by coadministering a peripheral opioid receptor antagonist (naloxone
      methiodide), a nitric oxide synthase (NOS) inhibitor (L-NMMA), a soluble guanylyl
      cyclase inhibitor (ODQ), a PKG inhibitor (KT-5823) or a K(+)(ATP)-channel blocker
      (glibenclamide) shows the involvement of a NO/cGMP/K(+)(ATP)-channel pathway.
      Accordingly the administration of loperamide produced, in osteosarcoma-bearing
      mice, an increase in the concentrations of NO metabolites, nitrites and nitrates,
      extracted from paws. The selective inhibitor of eNOS L-NIO, but not the
      inhibitors of nNOS (N-omega-propyl-L-arginine) or iNOS (1400w), blocked the
      effect of loperamide on osteosarcoma-induced hyperalgesia and also the endogenous
      opioid peripheral hypoalgesia that appears during the initial stages of the
      development of this osteosarcoma. Although this pathway also participates in the
      inhibitory effect of loperamide on the thermal hyperalgesia induced by
      administration of complete Freund's adjuvant, only selective inhibitors of nNOS
      or iNOS antagonized this effect. Our results demonstrate that the activation of a
      NO/cGMP/K(+)(ATP)-channel triggered by eNOS participates in the peripheral
      antihyperalgesic of loperamide on osteosarcoma-induced thermal hyperalgesia.

PMID- 17543352
TI  - Differential activation of protein kinases in the dorsal horn in vitro of normal
      and inflamed rats by group I metabotropic glutamate receptor subtypes.
AB  - Group I metabotropic glutamate receptors (mGluRs) contribute to spinal
      sensitization and synaptic plasticity but the underlying mechanisms are unknown.
      Here, group I mGluR modulation of evoked monosynaptic excitatory postsynaptic
      currents (EPSCs) in substantia gelatinosa (SG) neurones in vitro was investigated
      in juvenile rats. In addition, the role of group I mGluRs in dorsal horn neuronal
      Fos expression was determined in tetrodotoxin (TTX)-treated in vitro spinal cords
      of naive rats and those with Complete Freund's Adjuvant (CFA) peripheral
      inflammation. In the majority of SG neurones, (S)-3,5-dihydroxyphenylglycine
      (DHPG) reduced EPSCs and this effect was inhibited by the mGluR(5) antagonist 2
      methyl-6-(phenylethynyl)-pyridine (MPEP). Data for paired-pulse and spontaneous
      miniature excitatory postsynaptic currents (mEPSCs) suggest mGluR(5) acts
      presynaptically to reduce transmitter release. DHPG-induced reduction of EPSC
      amplitude operated via PKC, but not ERK, signalling cascade. In the dorsal horn
      of naive but not CFA rats, DHPG increased Fos expression and this was reduced by
      MPEP and both PKC and ERK inhibitors. In the CFA group, basal Fos expression was
      reduced by MPEP and the kinase inhibitors. These data infer a role for mGluR(5)
      in acute modulation of nociceptive synaptic efficacy within the dorsal horn and
      postsynaptic activation of transcription factors such as Fos that are implicated
      in activity-dependent neuroplastic adaptation. These actions are achieved by
      differential activation of PKC- and ERK-dependent transduction pathways.

PMID- 17543353
TI  - Pre- and postsynaptic effects of kainate on layer II/III pyramidal cells in rat
      neocortex.
AB  - Kainate receptors mediate both direct excitatory and indirect modulatory actions
      in the CNS. We report here that kainate has both pre- and postsynaptic actions in
      layer II/III pyramidal neurons of rat prefrontal cortex. Application of low
      concentration of kainate (50-500 nM) increased the amplitude of evoked excitatory
      postsynaptic currents (EPSCs) whereas higher concentrations (3 microM) caused a
      decrease. The frequency of spontaneous and miniature (action potential
      independent) EPSCs was increased by low concentrations of kainate without
      affecting their amplitudes, suggesting a presynaptic mechanism of action. The
      facilitatory and inhibitory effects of kainate were mimicked by the GluR5 subunit
      selective agonist ATPA. In addition to decreasing EPSC amplitudes, high
      concentrations of kainate and ATPA induced an inward current which was not
      blocked by AMPA- or NMDA-receptor antagonists GYKI52466 and D-APV, respectively.
      The inward currents were blocked by the AMPA/KA receptor antagonist CNQX,
      indicating the presence of postsynaptic kainate receptors. Single shock
      stimulation in the presence of GYKI52466 and D-APV evoked an EPSC which was
      blocked by CNQX. The GluR5 antagonist LY382884 changed paired-pulse facilitation
      to paired pulse depression, indicating that synaptically released glutamate can
      activate presynaptic kainate receptors. These results suggest that kainate
      receptors containing GluR5 subunits play a major role in glutamatergic
      transmission in rat neocortex, having both presynaptic modulatory and direct
      postsynaptic excitatory actions.

PMID- 17543354
TI  - Antidepressant treatments and function of glutamate ionotropic receptors
      mediating amine release in hippocampus.
AB  - Previous evidences showed that, besides noradrenaline (NA) and 5
      hydroxytryptamine (5-HT), glutamate transmission is involved in the mechanism of
      action of antidepressants (ADs), although the relations between aminergic and
      glutamatergic systems are poorly understood. The aims of this investigation were
      to evaluate changes in the function of glutamate AMPA and NMDA receptors produced
      by acute and chronic administration of the two ADs reboxetine and fluoxetine,
      selective inhibitors of NA and 5-HT uptake, respectively. Rats were treated
      acutely (intraperitoneal injection) or chronically (osmotic minipump infusion)
      with reboxetine or fluoxetine. Isolated hippocampal nerve endings (synaptosomes)
      prepared following acute/chronic treatments were labelled with [(3)H]NA or
      [(3)H]5-HT and [(3)H]amine release was monitored during exposure in superfusion
      to NMDA/glycine, AMPA or K(+)-depolarization. Acute and chronic reboxetine
      reduced the release of [(3)H]NA evoked by NMDA/glycine or by AMPA. The
      NMDA/glycine-evoked release of [(3)H]NA was also down-regulated by chronic
      fluoxetine. Only acute, but not chronic, fluoxetine inhibited the AMPA-evoked
      release of [(3)H]5-HT. The release of [(3)H]NA and [(3)H]5-HT elicited by K(+)
      depolarization was almost abolished by acute reboxetine or fluoxetine,
      respectively, but recovered during chronic ADs administration. ADs reduced NMDA
      receptor-mediated releasing effects in noradrenergic terminals after acute and
      chronic administration, although by different mechanisms. Chronic treatments
      markedly reduced the expression level of NR1 subunit in synaptic membranes. The
      noradrenergic and serotonergic release systems seem to be partly functionally
      interconnected and interact with glutamatergic transmission to down-regulate its
      function. The results obtained support the view that glutamate plays a major role
      in AD activity.

PMID- 17543355
TI  - Targeting the cholinergic system as a therapeutic strategy for the treatment of
      pain.
AB  - Acetylcholine mediates its effects through both the nicotinic acetylcholine
      receptors (ligand-gated ion channels) and the G protein-coupled muscarinic
      receptors. It plays pivotal roles in a diverse array of physiological processes
      and its activity is controlled through enzymatic degradation by
      acetylcholinesterase. The effects of receptor agonists and enzyme inhibitors,
      collectively termed cholinomimetics, in antinociception/analgesia are well
      established. These compounds successfully inhibit pain signaling in both humans
      and animals and are efficacious in a number of different preclinical and clinical
      pain models, suggesting a broad therapeutic potential. In this review we examine
      and discuss the evidence for the therapeutic exploitation of the cholinergic
      system as an approach to treat pain.

PMID- 17543356
TI  - Toward an understanding of the cerebral substrates of woman's orgasm.
AB  - The way women experience orgasm is of interest to scientists, clinicians, and
      laypeople. Whereas the origin and the function of a woman's orgasm remains
      controversial, the current models of sexual function acknowledge a combined role
      of central (spinal and cerebral) and peripheral processes during orgasm
      experience. At the central level, although it is accepted that the spinal cord
      drives orgasm, the cerebral involvement and cognitive representation of a woman's
      orgasm has not been extensively investigated. Important gaps in our knowledge
      remain. Recently, the astonishing advances of neuroimaging techniques applied in
      parallel with a neuropsychological approach allowed the unravelling of specific
      functional neuroanatomy of a woman's orgasm. Here, clinical and experimental
      findings on the cortico-subcortical pathway of a woman's orgasm are reviewed and
      compared with the neural basis of a man's orgasm. By defining the specific brain
      areas that sustain the assumed higher-order representation of a woman's orgasm,
      this review provides a foundation for future studies. The next challenge of
      functional imaging and neuropsychological studies is to understand the
      hierarchical interactions between these multiple cortical areas, not only with a
      correlation analysis but also with high spatio-temporal resolution techniques
      demonstrating the causal necessity, the temporal time course and the direction of
      the causality. Further studies using a multi-disciplinary approach are needed to
      identify the spatio-temporal dynamic of a woman's orgasm, its dysfunctions and
      possible new treatments.

PMID- 17543357
TI  - Stress, eating and the reward system.
AB  - An increasing number of people report concerns about the amount of stress in
      their life. At the same time obesity is an escalating health problem worldwide.
      Evidence is accumulating rapidly that stress related chronic stimulation of the
      hypothalamic-pituitary-adrenal (HPA) axis and resulting excess glucocorticoid
      exposure may play a potential role in the development of visceral obesity. Since
      adequate regulation of energy and food intake under stress is important for
      survival, it is not surprising that the HPA axis is not only the 'conductor' of
      an appropriate stress response, but is also tightly intertwined with the
      endocrine regulation of appetite. Here we attempt to link animal and human
      literatures to tease apart how different types of psychological stress affect
      eating. We propose a theoretical model of Reward Based Stress Eating. This model
      emphasizes the role of cortisol and reward circuitry on motivating calorically
      dense food intake, and elucidating potential neuroendocrine mediators in the
      relationship between stress and eating. The addiction literature suggests that
      the brain reward circuitry may be a key player in stress-induced food intake.
      Stress as well as palatable food can stimulate endogenous opioid release. In
      turn, opioid release appears to be part of an organisms' powerful defense
      mechanism protecting from the detrimental effects of stress by decreasing
      activity of the HPA axis and thus attenuating the stress response. Repeated
      stimulation of the reward pathways through either stress induced HPA stimulation,
      intake of highly palatable food or both, may lead to neurobiological adaptations
      that promote the compulsive nature of overeating. Cortisol may influence the
      reward value of food via neuroendocrine/peptide mediators such as leptin, insulin
      and neuropeptide Y (NPY). Whereas glucocorticoids are antagonized by insulin and
      leptin acutely, under chronic stress, that finely balanced system is
      dysregulated, possibly contributing to increased food intake and visceral fat
      accumulation. While these mechanisms are only starting to be elucidated in
      humans, it appears the obesity epidemic may be exacerbated by the preponderance
      of chronic stress, unsuccessful attempts at food restriction, and their
      independent and possibly synergistic effects on increasing the reward value of
      highly palatable food.

PMID- 17543358
TI  - Adolescent human immunodeficiency virus and sexually transmitted disease
      prevention programmes: are gender-blind approaches justified?
AB  - OBJECTIVE: To present findings that gender might be more predictive of human
      immunodeficiency virus (HIV) and sexually transmitted disease (STD) knowledge,
      and sexual behaviour, compared with participation in knowledge-based HIV
      prevention programmes. STUDY DESIGN: A cross-sectional study comparing students
      attending public high schools running an HIV and STD prevention programme. It is
      based on a study that evaluated the City of Houston HIV and STD prevention
      programme in public high schools. Comparison was initially between groups
      (intervention vs comparison) and subsequently between gender. The main variables
      for comparison were level of interest and knowledge of the subject of HIV and
      STD, and a range of sexual behaviour variables. METHODS: Self-administered
      questionnaires were used for eliciting both knowledge and behavioural data. A
      specific question required participants to rate their level of interest in the
      subject of HIV and STD on a scale of 1-4 (lowest to highest). The knowledge
      component was marked and scores awarded in percentage form. Descriptive
      statistical analysis was followed by stratified analysis. Finally, a select
      number of variables were used in a logistic regression model. STATA version 8 was
      the main statistical software. RESULTS: A significantly large proportion of girls
      reported the highest level of interest in the subject of HIV and STD (a score of
      4); had higher HIV and STD knowledge scores; and reported less risk-taking sexual
      behaviour compared with boys. The only variable in which boys faired better was
      condom use, reporting higher rates of condom use than girls. CONCLUSIONS: Gender
      blind HIV and STD prevention programmes seem to have a minimal effect on boys.
      Although a myriad of other factors influence male response to such programmes,
      the relatively low level of interest in the subject of HIV and STD among boys
      might be contributory. HIV and STD prevention programmes need to be re-designed
      using approaches that are more appealing to boys. Boys will otherwise remain the
      weak link and therefore the rate-limiting step in the quest for sexual behaviour
      change among adolescents.

PMID- 17543359
TI  - Risk factors associated with leptospirosis in dairy goats under tropical
      conditions in Brazil.
AB  - Serum samples from 248 adult dairy goats from 13 flocks with lowered fertility
      farmed in the Rio de Janeiro region of Brazil were examined for Leptospira
      antibodies by MAT with 24 serovars, cut off 100. A questionnaire was completed
      for each herd. Antibodies were detected in 20.8% of these goats, mainly to
      serovar Hardjo. Risk factors associated with seroprevalence to leptospirosis were
      the frequency of professional veterinary supervision (OR = 2.35), climate (OR =
      2.63) and grazing for more than 2h a day. Flock factors as size, type of milking
      and offering of food supplementation, as well as the location and topography, the
      type of animal housing or the presence of silos did not significantly affect
      seroprevalence. We suggest that a successful control program for goat
      leptospirosis should include a complete investigation of herd management
      practices, which could influence in the occurrence of the infection.

PMID- 17543360
TI  - Influence of iron and zinc status on cadmium accumulation in Bangladeshi women.
AB  - Cadmium is a widespread environmental contaminant present in food. The absorption
      in the intestine increases in individuals with low iron stores, but the effect of
      zinc deficiency is not clear. The aim of the present study was to assess the
      influence of iron and zinc status on cadmium accumulation in pregnant Bangladeshi
      women. We measured cadmium in urine from 890 women using inductively coupled
      plasma mass spectrometry (ICPMS). Further, we also measured ferritin and zinc in
      plasma. The median cadmium concentration in urine was 0.59 microg/L (adjusted to
      mean specific gravity of 1.012 g/mL). Analysis of covariance (ANCOVA) showed that
      urinary cadmium was associated with plasma ferritin and plasma zinc via a
      significant interaction between dichotomized plasma ferritin and plasma zinc. The
      analysis was adjusted for age and socioeconomic status. Women with low iron
      stores and adequate zinc status had significantly higher urinary cadmium compared
      to women with both adequate iron stores and zinc status. There was no difference
      in urinary cadmium between women with both low iron stores and zinc status
      compared to those with both adequate iron stores and zinc status. In conclusion,
      low iron stores were associated with increased cadmium accumulation, but only at
      adequate zinc status.

PMID- 17543361
TI  - Molecular characterization of L-amino acid oxidase from king cobra venom.
AB  - An L-amino acid oxidase from Ophiophagus hannah snake venom (Oh-LAAO) was
      purified by successive gel filtration, ion-exchange and heparin chromatography.
      Oh-LAAO did not induce platelet aggregation; however, it had potent inhibitory
      activity on platelet aggregation induced by ADP and U46619, but showed no effect
      on platelet aggregation induced by thrombin, mucetin, ristocetin and stejnulxin.
      By RT-PCR and 5'-RACE methods, the complete Oh-LAAO cDNA was cloned from the
      venom gland total RNA preparations. The cDNA sequence contains an open-reading
      frame (ORF) of 1476-bp, which encodes a protein of 491 amino acids comprising a
      signal peptide of 25 amino acids and 466-residue mature protein. The predicted
      protein sequence of Oh-LAAO was confirmed by N-terminal and trypsin-digested
      internal peptides sequencing together with peptide mass fingerprinting. cDNAs
      encoding for ORF of LAAOs from Bungarus fasciatus and B. multicinctus were cloned
      and reported in this study. In addition, partial cDNA encoding for Naja atra LAAO
      was also reported. Oh-LAAO shared approximately 50% protein sequence identity
      with other known snake venom LAAOs. Phylogenetic analysis indicated that Oh-LAAO
      is evolutionary distant to other snake venom LAAOs.

PMID- 17543362
TI  - The cytotoxicity of lingshuiol: a comparative study with amphidinol 2 on membrane
      permeabilizing activities.
AB  - The cytotoxicity of lingshuiol, a novel polyhydroxy compound with a linear carbon
      chain isolated from the cultured marine dinoflagellate Amphidinium sp., and that
      of amphidinol 2 (AM2) was compared with hepatocytes. Both lingshuiol and AM2 were
      toxic to primary rat hepatocytes with IC(50) values of 0.21 and 6.4muM,
      respectively. Meanwhile, lingshuiol or AM2 caused a rapid mitochondrial swelling
      and leakage of Ca(2+), underlying the change in permeability of mitochondria.
      Cyclosporin A, a specific inhibitor of mitochondrial permeability transition
      (MPT), could not affect these effects, indicating that CsA-sensitive MPT was not
      involved in the permeabilizing effects of lingshuiol or AM2. Sytox green tests
      further demonstrated that lingshuiol had a much stronger permeabilizing activity
      than AM2. Taken together, these results disclosed that lingshuiol had potent
      membrane permeabilizing activities, which might account for its cytotoxic effect.

PMID- 17543363
TI  - Forced selection of tRNA(Glu) reveals the importance of two adenosine-rich RNA
      loops within the U5-PBS for SIV(smmPBj) replication.
AB  - Simian immunodeficiency virus (SIV) and human immunodeficiency virus (HIV-1)
      preferentially select and use tRNA(Lys,3) as the primer for initiation of reverse
      transcription. Previous studies have shown that HIV-1 can be forced to use
      tRNA(Glu) if mutations are made within the primer-binding site (PBS) and a region
      upstream, A-loop, to be complementary to the 3'-terminal 18 nucleotides and
      anticodon loop of tRNA(Glu). To examine the primer preference of SIV, mutations
      were made within the PBS of SIV(smmPBj) to be complementary to tRNA(Glu).
      Analysis of the production of infectious virus revealed that SIV(smmPBj) with the
      PBS complementary to tRNA(Glu) retained approximately 80% infectivity of the wild
      type. However, modification of the U5 of SIV(smmPBj) to alter nucleotides to be
      complementary to the anticodon of tRNA(Glu), in combination with the PBS
      complementary to tRNA(Glu), drastically reduced the production of infectious
      SIV(smmPBj) to less than 1% that of wild type. The replication of SIV(smmPBj)
      with the PBS complementary to tRNA(Glu) was similar to that of the wild type
      virus, while the replication of SIV(smmPBj) with PBS and A-loop complementary to
      tRNA(Glu) was delayed compared to that of wild type virus. Analysis of the PBS
      regions revealed that the virus with the PBS complementary to tRNA(Glu) reverted
      quickly, within 4 days, to be complementary to tRNA(Lys,3), while the virus with
      PBS and A-loop complementary to tRNA(Glu) retained the PBS for a longer time
      during in vitro culture although following extended replication both the A-loop
      and PBS of SIV(smmPBj) reverted to be complementary to tRNA(Lys,3). RNA modeling
      of SIV(smmPBj) U5-PBS by m-fold revealed two potential A-loop regions. Mutations
      in either A-loop drastically effected replication in human PBMC. Analysis of the
      A-loops following in vitro replication revealed that both reverted to the wild
      type sequence. The results of these studies demonstrate that SIV(smmPBj), like
      HIV-1, preferentially utilizes tRNA(Lys,3) as a primer for reverse transcription
      for high level replication, but unlike HIV-1 selection may involve the use of two
      adenosine-rich loops.

PMID- 17543364
TI  - Borna disease virus P protein inhibits nitric oxide synthase gene expression in
      astrocytes.
AB  - Borna disease virus (BDV) is one of the potential infectious agents involved in
      the development of central nervous system (CNS) diseases. Neurons and astrocytes
      are the main targets of BDV infection, but little is known about the roles of BDV
      infection in the biological effects of astrocytes. Here we reported that BDV
      inhibits the activation of inducible nitric oxide synthase (iNOS) in murine
      astrocytes induced by bacterial LPS and PMA. To determine which protein of BDV is
      responsible for the regulation of iNOS expression, we co-transfected murine
      astrocytes with reporter plasmid iNOS-luciferase and plasmid expressing
      individual BDV proteins. Results from analyses of reporter activities revealed
      that only the phosphoprotein (P) of BDV had an inhibitory effect on the
      activation of iNOS. In addition, P protein inhibits nitric oxide production
      through regulating iNOS expression. We also reported that the nuclear factor
      kappa B (NF-kappaB) binding element, AP-1 recognition site, and interferon
      stimulated response element (ISRE) on the iNOS promoter were involved in the
      repression of iNOS gene expression regulated by the P protein. Functional
      analysis indicated that sequences from amino acids 134 to 174 of the P protein
      are necessary for the regulation of iNOS. These data suggested that BDV may
      suppress signal transduction pathways, which resulted in the inhibition of iNOS
      activation in astrocytes.

PMID- 17543365
TI  - Functional interplay between the B-box 2 and the B30.2(SPRY) domains of
      TRIM5alpha.
AB  - The retroviral restriction factors, TRIM5alpha and TRIMCyp, consist of RING and B
      box 2 domains separated by a coiled coil from carboxy-terminal domains. These
      carboxy-terminal domains (the B30.2(SPRY) domain in TRIM5alpha and the
      cyclophilin A domain in TRIMCyp) recognize the retroviral capsid. Here we show
      that some B-box 2 changes in TRIM5alpha, but not in TRIMCyp, resulted in
      decreased human immunodeficiency virus (HIV-1) capsid binding. The phenotypic
      effects of these B-box 2 changes on the restriction of retroviral infection
      depended on the potency of restriction and the affinity of the TRIM5alpha
      interaction with the viral capsid, two properties specified by the B30.2(SPRY)
      domain. Thus, some alterations in the TRIM5alpha B-box 2 domain apparently affect
      the orientation or conformation of the B30.2(SPRY) domain, influencing capsid
      recognition.

PMID- 17543366
TI  - Viral insertion in Evi12 causes expression of aberrant Grp94 mRNAs containing the
      viral gag myristylation motif.
AB  - Ecotropic Virus Integration site 12 (Evi12) is a common virus insertion site
      (cVIS) in retrovirally induced murine models of leukemia and lymphoma, suggesting
      an important role for this locus in these hematopoietic disorders. Evi12 is
      located near the promoter of the ER chaperone protein and Hsp90 family member
      Grp94. Here we show that viral insertion in Evi12 results in the expression of
      aberrant Grp94 transcripts in Cas-Br-MuLV as well as in AKXD induced
      hematopoietic tumors, demonstrating that Grp94 is a common viral target gene.
      While most transcripts encode for truncated forms of Grp94, transcripts
      containing viral gag sequences were detected in the leukemia cell line NFS107.
      Interestingly, these fusion transcripts encode for myristylated viral-Grp94
      fusion proteins that localize to the plasma membrane. Combined with recent
      evidence that myristylated forms of Hsp90 transform cells, our data suggest that
      myristylation of target genes may be an important mechanism in retrovirally
      mediated oncogenesis. Since retroviral insertion in Evi12 also affects the
      expression of a recently identified novel gene Grp94 neighboring nucleotidase
      (Gnn), located at the other side of Evi12, it appears that proviral insertion can
      lead to deregulation of two genes present in the same locus.

PMID- 17543367
TI  - Glycosylation of the dengue 2 virus E protein at N67 is critical for virus growth
      in vitro but not for growth in intrathoracically inoculated Aedes aegypti
      mosquitoes.
AB  - To determine the importance of dengue 2 virus (DEN2V) envelope (E) protein
      glycosylation, virus mutants in one or both of the N-linked glycosylation motifs
      were prepared. We found that while the E2 mutant virus (N153Q) replicated in
      mammalian and mosquito cells, the E1 (N67Q) and E1/2 (N67Q and N153Q) mutant
      viruses were unable to grow in mammalian cells. Infection of C6/36 mosquito cells
      with either the E1 or E1/2 mutants resulted in the introduction of a compensatory
      mutation, K64N, restoring glycosylation in the area. All mutants replicated
      similarly in inoculated Aedes aegypti mosquitoes, with no change in their
      mutations. These results suggest that N-linked glycosylation of the E protein is
      not necessary for DEN2V replication in mosquitoes, however N-linked glycosylation
      at amino acid N67 (or nearby N64) is critical for the survival of the virus in
      either mammalian or insect cell culture.

PMID- 17543369
TI  - Variability of fecal indicator bacteria in flowing and ponded waters in southern
      California: implications for bacterial TMDL development and implementation.
AB  - Recreational water quality is assessed by using water quality objectives for
      fecal indicator bacteria (FIB) including total coliform, fecal coliform (or E.
      coli), and/or Enterococcus. It is required under the Clean Water Act that a TMDL
      be developed for a bacteria-impaired water body. The development and
      implementation of bacterial TMDLs has proven challenging and often difficult due
      to unknown source(s) of FIB. This study found that FIB levels varied
      significantly in flowing water, ponded water, and associated sediment. FIB levels
      in isolated ponded water in waterways were significantly higher than in flowing
      water. Sediment under ponded water contained a great amount of FIB. Furthermore,
      FIB concentrations in ponded water tended to increase with increasing water
      temperature and to decrease with increasing water salinity. The result provides
      the field evidence of survival/growth of FIB in water and sediment under ambient
      conditions in southern California. A holistic approach including natural sources
      (e.g., a reference system) should be considered for practical and applicable
      purposes while developing and implementing bacterial TMDLs for pathogen-impaired
      waterbodies.

PMID- 17543370
TI  - Increased blood lead concentration during menstruation in teen female students.
AB  - Among many studies on the health effects associated with lead burden in human,
      none has addressed for menstrual cycle. Studies have reported that blood lead
      levels (BLLs) may increase as estrogen levels decrease. We conducted a study to
      test whether the BLLs vary during the menstrual cycle. The subjects were 138 teen
      girls recruited at a junior nursing college. Blood specimens were collected in
      non-menses days in September 2003 (baseline BLLs) and during days of the menses
      in December 2003 (between 72nd and 96th hours of the period for follow-up
      measures). The paired test for differences of BLLs was used to compare between
      these two measures. There were no significant differences in baseline
      characteristics between students who had participated in both the baseline and
      follow-up studies and students who had participated only in baseline study. The
      average BLLs measured during the menses was 0.20 microg/dL higher than that
      measured at the baseline study (p<0.01). This finding suggests that the average
      BLL was 7.6% increased at the menses among these teen girl students. In the
      future, the time to collect blood samples for measuring lead for women should be
      standardized.

PMID- 17543368
TI  - Induction of promyelocytic leukemia (PML) oncogenic domains (PODs) by
      papillomavirus.
AB  - Promyelocytic leukemia oncogenic domains (PODs), also called nuclear domain 10
      (ND10), are subnuclear structures that have been implicated in a variety of
      cellular processes as well as the life cycle of DNA viruses including
      papillomaviruses. In order to investigate the interplay between papillomaviruses
      and PODs, we analyzed the status of PODs in organotypic raft cultures of human
      keratinocytes harboring HPV genome that support the differentiation-dependent HPV
      life cycle. The number of PODs per nucleus was increased in the presence of HPV
      genomes selectively within the poorly differentiated layers but was absent in the
      terminally differentiated layers of the stratified epithelium. This increase in
      PODs was correlated with an increase in abundance of post-translationally
      modified PML protein. Neither the E2-dependent transcription nor viral DNA
      replication was reliant upon the presence of PML. Implications of these findings
      in terms of HPV's interaction with its host are discussed.

PMID- 17543372
TI  - Dynamics of platelet activation in diabetic and non-diabetic subjects during the
      course of an acute myocardial infarction.
AB  - INTRODUCTION: The dynamics of platelet activation during the course of a
      myocardial infarction is unknown but of great importance in terms of risk
      assessment and anti-thrombotic therapy. The aim of the present study was
      sequentially to analyse platelet activation in diabetic and non-diabetic subjects
      with an acute myocardial infarction. MATERIALS AND METHODS: We used a sensitive
      laser light scattering technique to assess platelet aggregation as a measure of
      activation. Measurements were made on the first, second, third and fifth day in
      hospital. Two hundred and forty-three patients with an acute myocardial
      infarction, of whom 48 had diabetes, were included. RESULTS: Platelet activation
      increased until the third in-hospital day in both diabetic and non-diabetic
      subjects, despite intense anti-thrombotic therapy. The activation was more
      pronounced in diabetic subjects from the time of hospital admission. Platelet
      activation tended to decrease after the third in-hospital day. CONCLUSIONS: We
      conclude that platelet activation increases rapidly at the onset of a myocardial
      infarction, despite aggressive anti-thrombotic treatment. The activation is more
      pronounced in diabetic subjects and tends to decrease within a few days. More
      targeted and effective anti-platelet therapy has the potential further to reduce
      cardiac and cerebral ischemic events following myocardial infarction and ongoing
      clinical trials are addressing this issue.

PMID- 17543371
TI  - Changes in estrogen/anti-estrogen activities in ponded secondary effluent.
AB  - Total estrogenic activity, measured using the yeast estrogen screen reporter gene
      bioassay, decreased from 60 pM (equivalent 17alpha-ethinylestradiol
      concentration) to an estimated 1.4 pM during a 24-hour period in which secondary
      effluent was held in a shallow infiltration basin. Over the same period, anti
      estrogenic activity, measured as an equivalent concentration of tamoxifen,
      increased from 35 to 260 nM, suggesting that antagonists produced during
      secondary effluent storage played a role in the apparent loss of estrogenic
      activity. Androgenic activity, measured over the same 24-hour period using the
      yeast androgen screen, was near or below the method detection limit (0.7 pM as
      testosterone). However, the same pond samples were clearly anti-androgenic. When
      whole-sample extracts were separated via adsorption and stepwise elution in
      alcohol/water solutions consisting of 20, 40 and 100% ethanol, the sum of
      estrogenic activities in derived fractions was always lower than the measured
      estrogenic activity in the whole-sample extracts. Summed anti-estrogenic
      activities in the same fractions, however, always exceeded values for
      corresponding whole-sample extracts. Results reinforce the importance of sample
      preparation steps (concentration of organics followed by estrogen/anti-estrogen
      separation) when measuring endocrine-related activities in chemically complex
      samples such as wastewater effluent. The potential complexity of relationships
      among estrogens, anti-estrogens and matrix organics suggests that additive models
      are of questionable validity for estimating whole-sample estrogenic activity from
      measurements involving sample fractions.

PMID- 17543373
TI  - Contribution of multiple thrombophilic and transient risk factors in the
      development of cerebral venous thrombosis.
AB  - INTRODUCTION: Cerebral venous thrombosis (CVT), deep vein thrombosis (DVT) and/or
      pulmonary embolism (PE) have been associated with thrombophilic defects. However,
      in contrast to DVT or PE, CVT is a rare disease. We performed a study to identify
      differences in thrombotic risk profile, predisposing to CVT rather than DVT or
      PE, particularly the contribution of oral contraception and 11 thrombophilic
      defects. MATERIALS AND METHODS: A single center case-control study (63 CVT cases
      and 209 controls with DVT or PE) was performed. RESULTS: Of CVT patients, 11% had
      experienced prior DVT or PE, and none had recurrent CVT at 5 years follow-up. CVT
      was more frequently observed in females (79% versus 51%, P<0.001). It was more
      often secondary (75% versus 50%, P<0.001), mainly due to the difference in age
      between both groups. At presentation of CVT and DVT/PE, oral contraceptives were
      used by 78% and 74% of non-pregnant fertile women (P=0.8), respectively. Any
      thrombophilic defect was demonstrated in 88% of CVT and 75% of DVT/PE patients
      (P=0.22), sex and age matched. Individual and two or more defects were equally
      distributed among both groups. CONCLUSIONS: We conclude that a majority of CVT
      and DVT or PE patients show single or multiple thrombophilic defects. At
      presentation, oral contraceptive intake was observed more frequently in CVT
      patients. However, no differences were observed in thrombotic risk profile
      between both groups of comparable age. Hence, additional unknown risk factors
      should be considered to explain the different sites of thrombosis in these
      patients.

PMID- 17543374
TI  - Ultrastructural and immunohistochemical characteristics of developing human
      pituitary gland.
AB  - The development and differentiation of the human pituitary gland and its
      relationship to other structures of the head were analysed in nine human embryos
      and fetuses aged 5-10 weeks old using morphological and immunohistochemical
      methods. In the 5th developmental week, the primordium of Rathke's pouch was
      closely associated with the cranial tip of the notochord, head mesenchyme and
      diencephalon. Cells of the Rathke's pouch displayed typical epithelial features
      that transformed into gland-like structures during development. Numerous Ki-67
      positive cells characterised the Rathke's pouch, the diencephalon
      (neurohypophysis) and the associated mesenchyme. The highest proliferation rate
      was noticed in the earliest developmental stage, while it significantly decreased
      in the 7th week of development. The first intermediate filaments to appear in the
      Rathke's pouch showed cytokeratin 8 immunolabelling which decreased with advanced
      maturation. The diencephalon and infundibulum displayed parallel immunolabelling
      of vimentin, glial fibrillary acidic protein (GFAP) and neurofilament protein
      (NF), while the surrounding mesenchyme showed only vimentin labelling. Changes in
      the labelling of Ki-67 proliferation marker and intermediate filament proteins in
      the developing human pituitary gland coincided with separation of the Rathke's
      pouch from the pharyngeal epithelium and subsequent differentiation of different
      parts of the gland.

PMID- 17543376
TI  - Sublingual immunotherapy in mite-sensitized children with atopic dermatitis: a
      randomized, double-blind, placebo-controlled study.
AB  - BACKGROUND: Atopic dermatitis often has an allergic component, and immunotherapy
      may therefore prove beneficial. OBJECTIVE: To assess the effect of sublingual
      immunotherapy (SLIT) in children with atopic dermatitis. METHODS: Children age 5
      to 16 years with atopic dermatitis (Scoring Atopic Dermatitis [SCORAD] > 7) and
      sensitization to dust mites alone, without food allergy or chronic asthma, were
      enrolled in a randomized, double-blind, placebo-controlled study and stratified
      according to disease severity. SLIT or placebo was given for 18 months in
      addition to standard therapy. SCORAD, visual analog scale, and rescue medication
      consumption were recorded at 3-month intervals. RESULTS: Fifty-six children were
      enrolled, and 28 were allocated to SLIT. Forty-eight completed the study, with 2
      dropouts in the active and 6 in the placebo group. The difference from baseline
      in the SCORAD was significant (P = .025) between the 2 groups starting from month
      9. Similarly, there was a significant reduction in the use of medications only in
      the active group. A trend toward significance was seen for the visual analog
      score only in the active group versus baseline (P = .07). A significant
      difference in the considered parameters was found only in patients with a mild
      moderate disease, whereas severe patients had only a marginal benefit. SLIT had
      to be discontinued in 2 patients because of exacerbation of dermatitis.
      CONCLUSION: Sublingual immunotherapy to dust mite improves mild-moderate atopic
      dermatitis. CLINICAL IMPLICATIONS: Sublingual immunotherapy may represent an
      additional therapeutic tool for the treatment of extrinsic atopic dermatitis in
      properly selected children.

PMID- 17543377
TI  - Modifications to an Fcgamma-Fcvarepsilon fusion protein alter its effectiveness
      in the inhibition of FcvarepsilonRI-mediated functions.
AB  - BACKGROUND: GE2, a human bifunctional Fcgamma-Fcvarepsilon fusion protein cross
      links FcgammaRIIb and FcvarepsilonRI on human mast cells and basophils and
      results in inhibition of FcvarepsilonRI-mediated functions. OBJECTIVE: Three
      modified Fcgamma-Fcvarepsilon (GE) proteins were compared with GE2 for their
      effect on inhibition of FcvarepsilonRI-mediated cellular responses. METHODS: GE2
      was modified to potentially improve its therapeutic efficacy by increasing
      binding to FcgammaRIIb (GE S mutant) and decreasing binding to FcgammaRIII (GE H
      mutant) or reversing the Fcgamma and Fcvarepsilon domains and removing nonhuman
      linker sequences (E2G). These proteins were tested for their ability to bind a
      basophil-like cell line, block FcvarepsilonRI-mediated degranulation in human
      basophils, and inhibit passive cutaneous anaphylaxis in human FcvarepsilonRIalpha
      transgenic mice. RESULTS: All 4 GE proteins bound cells that express
      FcvarepsilonRI and FcgammaRIIb, although the original GE2 retained the strongest
      ability to bind to these cells. E2G was as effective as GE2 in its ability to
      inhibit anti-Fel d 1 IgE-mediated histamine release from human basophils and
      block passive cutaneous anaphylaxis reactions. The GE S and GE H mutants were
      less effective. CONCLUSION: Optimization of GE2 as an inhibitor of FcvarepsilonRI
      mediated functions showed that effectiveness was maintained when potentially
      immunogenic linker sequences were removed and Ig domain positions were reversed,
      but specific residue changes within the IgG C(H)2 domain aimed at enhancing GE2's
      inhibitory function by increasing FcgammaRII binding or additionally decreasing
      FcgammaRIII binding were not beneficial. CLINICAL IMPLICATIONS: GE2 and E2G
      molecules are effective inhibitors of FcvarepsilonRI-mediated degranulation and
      are of interest as potential therapeutics for IgE-mediated allergic reactions.

PMID- 17543375
TI  - Genetic variation in S-nitrosoglutathione reductase (GSNOR) and childhood asthma.
AB  - BACKGROUND: S-nitrosothiols are potent endogenous bronchodilators depleted in
      asthmatic airway lining fluid. S-nitrosoglutathione reductase (GSNOR; also known
      as alcohol dehydrogenase 5 or formaldehyde dehydrogenase) catalyzes the
      metabolism of S-nitrosoglutathione (GSNO) and controls intracellular levels of S
      nitrosothiols. GSNOR knockout mice have increased lung S-nitrosothiol levels and
      are therefore protected from airway hyperresponsiveness after methacholine or
      allergen challenge. OBJECTIVE: We sought to investigate whether genetic variation
      in GSNOR is associated with childhood asthma and atopy. METHODS: We genotyped 5
      tagging and 2 additional single nucleotide polymorphisms (SNPs) in GSNOR in 532
      nuclear families consisting of asthmatic children aged 4 to 17 years and both
      parents in Mexico City. Atopy was determined by means of skin prick testing.
      RESULTS: Carrying 1 or 2 copies of the minor allele of SNP rs1,154,404 was
      associated with decreased risk of asthma (relative risk [RR], 0.77; 95% CI, 0.61
      0.97; P = .028 for 1 copy and RR, 0.66; 95% CI, 0.44-0.99; P = .046 for 2
      copies). Homozygosity for the minor allele of SNP rs28,730,619 was associated
      with increased risk of asthma (RR, 1.60; 95% CI, 1.13-2.26; P = .0077). Haplotype
      analyses supported the single SNP findings. GSNOR SNPs were not associated with
      the degree of atopy. CONCLUSION: This is the first study of genetic polymorphisms
      in GSNOR and asthma. These data suggest that genetic variation in GSNOR might
      play a role in asthma susceptibility. CLINICAL IMPLICATIONS: The association of
      GSNOR polymorphisms with asthma suggests a potential therapeutic target.

PMID- 17543378
TI  - Comparison of controlled internal drug release device and melengesterol acetate
      as progestin sources in an estrous synchronization protocol for beef heifers.
AB  - The objectives of this experiment were to compare estrous synchronization
      responses and AI pregnancy rates of beef heifers using protocols that included
      either CIDR or MGA as the progestin source. The hypotheses tested were that: (1)
      estrous synchronization responses after (a) progestin removal, and (b)
      PGF(2alpha); and, (2) AI pregnancy rates, do not differ between heifers
      synchronized with either progestin source. At the start of the experiment (Day 0)
      in both years, heifers were assigned randomly to receive, MGA supplement for 14
      days (MGA-treated; n=79) or CIDR for 14 days (CIDR-treated; n=77). On Day 14
      progestin was removed and heifers were observed for estrus up to and after
      PGF(2alpha) on Days 31 and 33 for CIDR-treated and MGA-treated heifers,
      respectively. Heifers that exhibited estrus within 60h after PGF(2alpha) were
      inseminated by AI 12h later; the remaining heifers were inseminated at 72h after
      PGF(2alpha) and given GnRH (100mug). More (P<0.05) CIDR-treated heifers exhibited
      estrus within 120h after progestin removal than MGA-treated heifers. Intervals to
      estrus after progestin removal were shorter (P<0.05) for CIDR-treated heifers
      than MGA-treated heifers. More (P<0.05) CIDR-treated heifers exhibited estrus and
      were inseminated within 60h after PGF(2alpha) than MGA-treated heifers. Pregnancy
      rates did not differ (P>0.10) between MGA-treated (66%) and CIDR-treated (62%)
      heifers. In conclusion, the use of CIDR as a progestin source in a 14-day
      progestin, PGF(2alpha), and timed AI and GnRH estrous synchronization protocol
      was as effective as the use of MGA to synchronize estrus and generate AI
      pregnancies in beef heifers.

PMID- 17543379
TI  - Use of a low-volume uterine flush for diagnosing endometritis in chronically
      infertile mares.
AB  - Low-volume uterine flush (n=401) was performed in 308 infertile mares to diagnose
      endometritis. Mares evaluated were either barren after three or more breedings or
      had two or more unsuccessful embryo recovery attempts during consecutive cycles.
      Culture results were compared with cytological and histological findings, efflux
      clarity and pH to substantiate that the micro-organisms recovered were truly
      pathogens. Cytological specimens were evaluated for presence of epithelial and
      inflammatory cells, bacteria, yeast and debris. Endometrial biopsies (n=110) were
      examined for the presence of neutrophils in the stratum compactum. Micro
      organisms were recovered in 282/401 (70%) of low-volume flushes; E. coli was most
      frequently isolated (42.2%), followed by beta hemolytic Streptococcus (37.6%).
      Efflux clarity of 318 flushes was clear (n=109), cloudy (n=149), or mucoid
      (n=60). Isolation of micro-organisms was highly associated with cloudy and mucoid
      effluxes (P<0.001), debris on cytological specimens (P<0.001), increased efflux
      pH (P<0.003), and neutrophils on endometrial biopsy (P<0.01). E. coli was
      associated with debris on cytological smear (P<0.002), whereas beta hemolytic
      Streptococcus was associated with increased efflux pH (P<0.002). Using the
      presence of neutrophils in a tissue specimen as the "best standard" for
      diagnosing endometritis, the sensitivity of flush culture was 0.71 and for flush
      cytology was 0.8, whereas the specificity was 0.86 and 0.67, respectively.
      Neutrophils in uterine flushes under-reported inflammation; only 86/282 positive
      cultures were positive on cytology. The clinical estimate of a contaminated
      (false positive) flush culture was 11%, if a false positive was defined as
      positive culture with clear efflux and no debris or neutrophils on cytology
      (26/228). In conclusion, a low-volume uterine flush was a rapid, accurate method
      for identifying mares with chronic endometritis. When micro-organisms were
      recovered, endometritis was confirmed by efflux clarity, pH and cytological
      findings of debris, bacteria, or neutrophils. E. coli was most commonly isolated
      and it appeared to differ in pathogenicity from beta hemolytic Streptococcus.

PMID- 17543380
TI  - Early pre-pubertal exposure to low-dose oral di(2-ethylhexyl) phthalate does not
      affect sperm plasma membrane stability, acrosomal integrity or chromatin
      structure in the post-pubertal boar.
AB  - This study aimed to determine whether pre-pubertal exposure in boars to di(2
      ethylhexyl) phthalate (DEHP), a plasticizer reported to have toxic effects on
      rodent reproduction, would affect the sperm ability to undergo capacitation and
      acrosome reaction (AR) in vitro or give rise to a higher degree of chromatin
      instability associated with acid-induced denaturation. Spermatozoa were collected
      from 16 boars (n=8/group) 8-9 months of age, exposed to 300mg/kg body weight of
      DEHP or placebo per os three times a week, from 3 to 7 weeks of age. The
      spermatozoa were cryopreserved and examined post-thaw by flow cytometry for their
      ability to capacitate in vitro when exposed to the effector bicarbonate and to
      acrosome-react when exposed to calcium ionophores, using the lipid stain
      Merocyanine-540 (m-540), and peanut agglutinin-fluorescein isothiocyanate,
      respectively, as probes. The ability of the DNA to sustain denaturation in vitro
      was tested using a sperm chromatin structure assay (SCSA). No significant
      differences between the DEHP-exposed group and controls were found for any of the
      sperm attributes examined. Frozen-thawed spermatozoa showed similar rates of non
      capacitated cells between groups, and were capacitated at similar rates. Rates of
      induced ARs were also similar. Values of DNA denaturation were low and showed no
      differences between groups. In conclusion, pre-pubertal exposure to DEHP does not
      seem, under the conditions of the present experiment, to affect the ability of
      frozen-thawed spermatozoa collected post-puberty to capacitate or acrosome-react
      (the main requisites for fertilization) or to present damage in their nuclear
      genome.

PMID- 17543381
TI  - Is there a relationship between the chromatin status and DNA fragmentation of
      boar spermatozoa following freezing-thawing?
AB  - In this study a radioisotope method, which is based on the quantitative
      measurements of tritiated-labeled actinomycin D ((3)H-AMD) incorporation into the
      sperm nuclei ((3)H-AMD incorporation assay), was used to assess the chromatin
      status of frozen-thawed boar spermatozoa. This study also tested the hypothesis
      that frozen-thawed spermatozoa with altered chromatin were susceptible to DNA
      fragmentation measured with the neutral comet assay (NCA). Boar semen was diluted
      in lactose-hen egg yolk-glycerol extender (L-HEY) or lactose ostrich egg yolk
      lipoprotein fractions-glycerol extender (L-LPFo), packaged into aluminum tubes or
      plastic straws and frozen in a controlled programmable freezer. In Experiment 1,
      the chromatin status and DNA fragmentation were measured in fresh and frozen
      thawed spermatozoa from the same ejaculates. There was a significant increase in
      sperm chromatin destabilization and DNA fragmentation in frozen-thawed semen as
      compared with fresh semen. The proportions of spermatozoa labeled with (3)H-AMD
      were concurrent with elevated levels of sperm DNA fragmentation in K-3 extender,
      without cryoprotective substances, compared with L-HEY or L-LPFo extender.
      Regression analysis revealed that the results of the (3)H-AMD incorporation assay
      and NCA for frozen-thawed spermatozoa were correlated. Boars differed
      significantly in terms of post-thaw sperm DNA damage. In Experiment 2, the
      susceptibility of sperm chromatin to decondensation was assessed using a low
      concentration of heparin. Treatment of frozen-thawed spermatozoa with heparin
      revealed enhanced (3)H-AMD binding, suggesting nuclear chromatin decondensation.
      The deterioration in post-thaw sperm viability, such as motility, mitochondrial
      function and plasma membrane integrity, was concurrent with increased chromatin
      instability and DNA fragmentation. This is the first report to show that freezing
      thawing procedure facilitated destabilization in the chromatin structure of boar
      spermatozoa, resulting in an unstable DNA that was highly susceptible to
      fragmentation.

PMID- 17543382
TI  - Systematic review of the chemical composition of contemporary dental adhesives.
AB  - Dental adhesives are designed to bond composite resins to enamel and dentin.
      Their chemical formulation determines to a large extent their adhesive
      performance in clinic. Irrespective of the number of bottles, an adhesive system
      typically contains resin monomers, curing initiators, inhibitors or stabilizers,
      solvents and sometimes inorganic filler. Each one of these components has a
      specific function. The aim of this article is to systematically review the
      ingredients commonly used in current dental adhesives as well as the properties
      of these ingredients. This paper includes an extensive table with the chemical
      formulation of contemporary dental adhesives.

PMID- 17543383
TI  - An Hsp70 peptide initiates NK cell killing of leukemic blasts after stem cell
      transplantation.
AB  - In contrast to solid tumors, leukemic blasts frequently present both Hsp70 and
      HLA-E on their cell surface and thereby present activating and inhibitory signals
      to CD94(+) NK cells. In the first 12 months after stem cell transplantation (SCT)
      CD94(+) NK cells clearly dominate over CD3(+)/CD16(-)/56(-) T and
      CD3(+)/CD16(+)/56(+) NK-like T cells. An incubation of post-SCT-derived
      peripheral blood lymphocytes with the Hsp70 peptide TKD and IL-15 enhances the
      cell surface density of CD56/CD94 and initiates the cytolytic activity of NK
      cells against Hsp70/HLA-E double-positive autologous and allogeneic leukemic
      blasts. Hsp70 was identified as the target structure for TKD-activated NK cells.

PMID- 17543384
TI  - Understanding and addressing the "neglect of neglect:" digging into the molehill.

PMID- 17543385
TI  - Proteomic analyses indicate induction of hepatic carbonyl reductase/20beta
      hydroxysteroid dehydrogenase B in rainbow trout exposed to sewage effluent.
AB  - Proteomic analyses were performed to identify regulated liver proteins in rainbow
      trout (Oncorhynchus mykiss) caged upstream and downstream from a sewage treatment
      works (STW). Two-dimensional gel electrophoresis, image analysis and FT-ICR mass
      spectrometry revealed four regulated protein spots. The three down-regulated
      spots contained betaine aldehyde dehydrogenase, lactate dehydrogenase and an
      unidentified protein respectively. The only up-regulated spot consisted of both
      mitochondrial ATP synthase alpha-subunit and carbonyl reductase/20beta
      hydroxysteroid dehydrogenase (CR/20beta-HSD). Further studies using quantitative
      PCR revealed a 13.5-fold induction of CR/20beta-HSD B mRNA following STW effluent
      exposure. The CR/20beta-HSD B gene was not regulated by 17alpha-ethinylestradiol,
      suggesting that its induction downstream from the STW is due to other factors
      than exposure to estrogens. Image analysis was initially performed on four gels
      from each group. These analyses suggested 15 regulated spots. However, validation
      of the 15 spots by increasing the number of replicates confirmed only four
      regulated spots. Hence, the present study also demonstrates the need for
      sufficient biological/technical replication in the interpretation of proteomic
      data.

PMID- 17543386
TI  - Nodavirus increases the expression of Mx and inflammatory cytokines in fish
      brain.
AB  - Nodavirus has become a serious pathogen for a wide range of cultured marine fish
      species. In the present work, the expression of genes related to immune and
      inflammatory responses of sea bream (Sparus aurata L.), considered as non
      susceptible species, was studied both in vitro and in vivo. No replication of the
      virus was observed in head kidney macrophages and blood leukocytes. Moreover, the
      enhancement of expression of several immune genes (tumor necrosis factor alpha
      (TNFalpha), interleukin-1-beta (IL-1beta), interferon-induced Mx protein) was not
      detected in both head kidney macrophages and blood leucocytes in response to an
      in vitro infection with nodavirus. However, in vivo, nodavirus was detected 1 day
      post-infection (p.i.) by a reverse transcription-polymerase chain reaction (RT
      PCR) in blood, liver, head kidney and brain of experimentally infected sea bream,
      while its presence clearly decreased in blood after 3 days p.i. Also, a
      transitory increment of the expression of TNFalpha and IL-1beta was detected in
      the brain of intramuscular (i.m.) infected sea bream 3 days p.i. In head kidney,
      the over expression of TNFalpha was only observed 1 day p.i. The expression of
      Mx, an interferon induced gene, was increased in brain and head kidney of
      infected sea bream, reaching values of 1300-fold compared to controls in brain
      three days post-infection. For comparative purposes, we analyzed the expression
      of the same genes on a susceptible species, such as sea bass (Dicentrarchus
      labrax) and, although the same pattern of expression was observed both in brain
      and kidney, the magnitude was different mainly in the case of brain, the key
      organ of the infection, where higher expression of TNFalpha and lower expression
      of Mx compared with control was observed.

PMID- 17543387
TI  - Activation of neutrophils by a novel triggering immunoglobulin-like receptor MAIR
      IV.
AB  - Neutrophils play a central role in host defenses against infectious microbial
      pathogens. However, molecular basis for their triggering signals has been
      incompletely understood. Here, we show molecular and functional characteristics
      of myeloid-associated immunoglobulin-like receptor (MAIR)-IV. MAIR-IV was
      preferentially expressed on neutrophils in the peripheral blood, bone marrow,
      peritoneal cavity and spleen. MAIR-IV physically associates with immunoreceptor
      tyrosine based activating motif (ITAM)-bearing adaptor FcRgamma chain. Cross
      linking MAIR-IV with anti-MAIR-IV monoclonal antibody significantly induced
      secretion of proinflammatory cytokines TNF-alpha and IL-6 from neutrophils. Thus,
      MAIR-IV may regulate activation of neutrophils and play an important role for
      innate immunity.

PMID- 17543388
TI  - Peripapillary changes detected by optical coherence tomography in eyes with high
      myopia.
AB  - OBJECTIVE: To investigate the morphologic alterations around the optic disc by
      optical coherence tomography (OCT) in eyes with high myopia. DESIGN:
      Observational case series. PARTICIPANTS: One hundred twenty-seven eyes (69
      patients) with high (> or =-8.00 diopters [D]) myopia were included. In addition,
      46 emmetropic (+1.00 to -1.00 D) eyes and 40 eyes with low (<-6.00 D) myopia were
      examined as controls. METHODS: The participants had ophthalmologic examinations
      including stereoscopic fundus observations, OCT examinations, and perimetry. For
      OCT, multiple horizontal and vertical OCT scans were obtained around the optic
      disc and fovea in each patient. MAIN OUTCOME MEASURES: The presence of a
      peripapillary detachment in eyes with pathologic myopia (PDPM) around and within
      the area of myopic conus, and the vascular microfolds and retinoschisis at the
      site of the retinal vessels at the conus edge were evaluated. RESULTS: A PDPM was
      detected by OCT in 14 eyes (11.0%). A PDPM was seen in the OCT images as a
      hyporeflective space intrachoroidally and subretinally. Hyporeflective spaces
      resembling PDPMs were also observed within the tissue posterior to the conus in
      eyes without the typical ophthalmoscopic yellow-orange lesions. Eyes with PDPM
      had glaucomalike visual field defects more frequently than eyes without PDPM.
      Pitlike structures within the conus were observed ophthalmoscopically in 3 eyes
      with high myopia, and OCT examinations revealed the presence of cystic structures
      with an opening toward the vitreous cavity at the corresponding sites. Microfolds
      in the retinal vessels were detected at the conus edge in 58 of the highly myopic
      eyes (45.0%), and 28 of these eyes had retinoschisis at the site of the retinal
      vessels. Fifteen of these 28 eyes showed an extension of the retinoschisis along
      the temporal retinal vessels toward the macula, and 9 of these 15 eyes had myopic
      foveoschisis. None of these changes (PDPM, pitlike structures, microfolds, and
      retinoschisis) were detected in controls. CONCLUSIONS: The OCT examinations
      demonstrated different types of abnormalities around the optic disc in highly
      myopic eyes. These changes might be related to the visually disabling
      complications, such as visual field loss and myopic foveoschisis, seen in highly
      myopic eyes.

PMID- 17543389
TI  - Clinical characterization of retinal capillary hemangioblastomas in a large
      population of patients with von Hippel-Lindau disease.
AB  - OBJECTIVE: To report the epidemiology and ocular phenotype of retinal capillary
      hemangioblastomas associated with von Hippel-Lindau (VHL) disease in a large
      cohort of patients and to correlate patient and ocular characteristics to visual
      morbidity in this population. DESIGN: Cross-sectional study. PARTICIPANTS: In 220
      unrelated pedigrees, 335 patients affected with VHL disease and retinal capillary
      hemangioblastomas (RCHs) in at least 1 eye. METHODS: Demographics of the patient
      population were recorded and the ocular phenotype of each patient was obtained
      with a comprehensive ocular examination. MAIN OUTCOME MEASURES: The patient
      population was characterized and the ocular phenotype described in relationship
      to tumor location, number, and extent of retinal involvement. Correlations
      between patient demographics, ocular phenotype, and visual function were
      analyzed. RESULTS: We detected RCHs unilaterally in 42.1% and bilaterally in
      57.9% of patients. No correlation was detected between the age, gender, or
      laterality of involvement. Of involved eyes, 86.6% had tumors that could be
      individually visualized; of these, tumors were commonly found in the peripheral
      retina (84.7%) only, and less commonly in the juxtapapillary area (15.3%). The
      tumor count in the periphery averaged 2.5+/-1.8 per eye, with 25.2% of eyes
      having >1 quadrant of retinal involvement. Of involved eyes, 13.4% were
      enucleated or prephthsical; approximately 1 in 5 patients had > or =1 eyes so
      affected. Severe visual impairment (visual acuity < or =20/160) in affected eyes
      were more likely to be associated with increasing age, the presence of
      juxtapapillary lesions, and an increasing number and extent of peripheral
      lesions. CONCLUSIONS: This large cohort of VHL patients with RCHs has enabled a
      systematic and quantitative characterization of the demographics, ocular
      features, and visual function in VHL disease. Clinical correlations between the
      visual morbidity and ocular features of the disease were also performed,
      producing measures that can help clinicians to estimate visual prognoses better
      based on the ocular phenotype of the disease.

PMID- 17543390
TI  - Local shaping of function in the motor cortex: motor contrast, directional
      tuning.
AB  - In this review we bring together three different lines of evidence to bear on the
      issue of local shaping of function in the motor cortex. The first line of
      evidence comes from the description by Cajal (1904) of the recurrent collaterals
      of pyramidal cell axons in the precentral gyrus. The second line of evidence
      comes from the electrophysiological study of the functional effects of these
      collaterals [Stefanis, C., Jasper, H. 1964a. Intracellular microelectrode studies
      of antidromic responses in cortical pyramidal tract neurons. J. Neurophysiol. 27,
      828-854.; Stefanis, C., Jasper, H. 1964b. Recurrent collateral inhibition in
      pyramidal tract neurons. J. Neurophysiol. 27, 855-877.] and associated
      interneurons [Stefanis, C. 1969. Interneuronal mechanisms in the cortex. In: The
      Interneuron, Brazier, M.A.B. (ed.), Berkeley, CA: University of California Press,
      pp. 497-526.] using intracellular recordings. And third came the discovery of
      directional tuning in the motor cortex [Georgopoulos, A.P., Kalaska, J.F.,
      Caminiti, R., Massey, J.T. 1982. On the relations between the direction of two
      dimensional arm movements and cell discharge in primate motor cortex. J.
      Neurosci. 2, 1527-1537.] in the behaving monkey. We hazard the hypothesis that
      the bell-shaped directional tuning curve is the outcome of orderly, local
      neuronal interactions in the motor cortex in which the recurrent pyramidal cell
      collaterals play a crucial role. Specifically, we propose that these collaterals
      and the intercalated interneurons they impinge upon serve to spatially sharpen
      the motor cortical activation to a locus corresponding to the direction of the
      intended movement. Thus, the originally proposed role of the pyramidal cell
      collaterals in enhancing "motor contrast" [Stefanis, C. 1969. Interneuronal
      mechanisms in the cortex. In: The Interneuron, Brazier, M.A.B. (ed.), Berkeley,
      CA: University of California Press, pp. 497-526.] would translate to creating a
      "directional tuning field" on the motor cortical surface, where the enhanced
      motor contrast would correspond to high activity at the center of directional
      field, and the suppression of the fringe would correspond to lower activity at
      the periphery of the field, resulting, together in spatial tuning.

PMID- 17543391
TI  - Neuroactive steroids and peripheral neuropathy.
AB  - Peripheral neuropathy, either inherited or acquired, represents a very common
      disorder for which effective clinical treatments are not available yet.
      Observations here summarized indicate that neuroactive steroids, such as
      progesterone, testosterone and their reduced metabolites, might represent a
      promising therapeutic option. Peripheral nerves are able to synthesize and
      metabolize neuroactive steroids and are a target for these molecules, since they
      express classical and non-classical steroid receptors. Neuroactive steroids
      modulate the expression of key transcription factors for Schwann cell function,
      regulate Schwann cell proliferation and promote the expression of myelin proteins
      involved in the maintenance of myelin multilamellar structure, such as myelin
      protein zero and peripheral myelin protein 22. These actions may result in the
      protection and regeneration of peripheral nerves affected by different forms of
      pathological alterations. Indeed, neuroactive steroids are able to counteract
      biochemical, morphological and functional alterations of peripheral nerves in
      different experimental models of neuropathy, including the alterations caused by
      aging, diabetic neuropathy and physical injury. Therefore, neuroactive steroids,
      pharmacological agents able to increase their local synthesis and synthetic
      ligands for their receptors have a promising potential for the treatment of
      different forms of peripheral neuropathy.

PMID- 17543392
TI  - Predictors of outcome of group and internet-based cognitive behavior therapy.
AB  - BACKGROUND: Little is known about which participant characteristics determine the
      effectiveness of various types of cognitive behavior therapy for sub-threshold
      depression. The aim of this study was to investigate which characteristics
      predict treatment outcome of group and internet-based interventions for sub
      threshold depression, with a special focus on (i) the five main personality
      factors, and (ii) their different predictive power in the different types of
      treatment. METHODS: Eighty-five women and 45 men (mean age=55 years, S.D.=4.4)
      were randomly assigned to a group treatment and an internet-based treatment. The
      outcome measure was the difference between pre-treatment and post-treatment BDI
      scores. Analyses of Covariance were conducted to examine which participant
      characteristics could predict outcome for the two different types of treatment.
      RESULTS: Higher baseline BDI scores (F(1,111)=52.88, p<.01), female gender
      (F(1,111)=6.45, p=.01), and lower neuroticism scores (F(1,111)=7.24, p=.01)
      predicted better outcome after both treatments. In the group intervention,
      participants with higher altruism scores improved significantly more after
      treatment (F(1,111)=3.94, p=.05) compared to the internet-based condition.
      LIMITATIONS: Axis-II disorders were not considered; the study assessed
      personality traits rather than personality disorders. CONCLUSIONS: Outcomes of
      different types of cognitive behavior therapy for sub-threshold depression are
      partly predicted by different participant characteristics. Neuroticism was
      associated with worse outcomes in both types of treatment, while altruism seems
      to be exclusively related to more favorable outcomes in the group treatment.

PMID- 17543393
TI  - Differential cytokine gene expression in CD4+ and CD8+ T cell subsets of calves.
AB  - The distinct patterns of cytokine expression in CD4+ and CD8+ T cells are well
      understood in mice and humans. However, little information is available about
      cytokine expression in bovine CD4+ and CD8+ T cells. In this study, mRNA
      expression of 19 different cytokines was analyzed in CD4+ and CD8+ T cells of
      calves with or without Concanavalin A (Con A) stimulation. CD4+ and CD8+ T cell
      populations were enriched to 98% purity by positive selection using magnetic cell
      sorting (MACS). CD4+ T cells spontaneously expressed the mRNAs of interleukin
      1alpha (IL-1alpha), IL-1beta, IL-2, IL-6, IL-7, IL-8, IL-10, IL-18, IFN-gamma,
      TNF-alpha, TNF-beta and TGF-beta, and augmented the mRNA expression of IL-10, IFN
      gamma and TNF-beta after Con A stimulation. The mRNAs of IL-3, IL-4, IL-5, IL-13
      and GM-CSF were newly expressed in Con A-stimulated CD4+ T cells. CD8+ T cells
      displayed spontaneous mRNA expression of IL-6, IL-18, TNF-alpha, TNF-beta and TGF
      beta, and newly expressed the mRNA of IL-2, IL-7, interferon-gamma (IFN-gamma)
      and GM-CSF after Con A stimulation. It was found that CD4+ T cells expressed the
      mRNA of 17 cytokines except for IL-12 and IL-15, while CD8+ T cells expressed
      only the mRNA of 9 cytokines after Con A stimulation. The profile of cytokine
      mRNA expression was substantially different in the CD4+ and CD8+ T cells of
      calves, indicating that CD4+ T cells can be distinguished from CD8+ T cells by
      the cytokine gene expression of IL-1alpha, IL-1beta, IL-3, IL-4, IL-5, IL-8, IL
      10 and IL-13. Differential cytokine expression between CD4+ and CD8+ T cells
      serve to interpret an individual function of T cell subsets in the immune system
      of calves.

PMID- 17543394
TI  - Otitis media referrals - the general practitioner perspective.
AB  - OBJECTIVE: Otitis media management involves both primary and specialist health
      care. The present study used data on GP referrals to estimate the proportion of
      children with otitis media referred from primary to specialist care, study
      variation in referral pattern and factors that influence GP behaviour. METHODS:
      Data on general practitioners' view on collaborative aspects of specialist health
      care was collected in a cross-sectional questionnaire survey among all Norwegian
      GPs in 2004 (N=1633). The outcome of interest was referral routines for otitis
      media at first visit and at follow-up. RESULTS: Mean referral for otitis media
      was 22%, most commonly at follow-up visit. Twenty-seven percent of children with
      otitis media were sent to ENT departments and 73% to practicing
      otolaryngologists. Variation in referral pattern among GPs was moderate. GPs with
      specialty in general medicine had 6% fewer referrals. Separate analysis on
      referral to practicing otolaryngologists showed that GP work load and
      availability to practicing specialists increased referral, whereas availability
      to hospital services reduced the probability. CONCLUSION: In Norway, otitis media
      management mainly takes place in primary care. Completed specialty in general
      medicine reduces referrals and non-medical factors influence referral behaviour.
      We suggest that learning groups may contribute to update knowledge in primary
      care and fewer referrals to specialists.

PMID- 17543396
TI  - Construction of a cysteine protease deficient Bombyx mori multiple
      nucleopolyhedrovirus bacmid and its application to improve expression of a fusion
      protein.
AB  - The bacmid system of BmMNPV with cysteine protease gene deletion (CPD-BmMNPV
      bacmid) was constructed using the lambda recombination system. The protease
      activities of Bombyx mori cells and silkworm larvae infected with this CPD-BmMNPV
      bacmid were reduced by 94% and 85%, respectively. By using this system, a GFP(uv)
      beta1,3-N-acetylglucosaminyltransferase 2 (GFP(uv)-beta3GnT2) fusion protein was
      successfully expressed in silkworm larvae with less protein degradation and
      without larvae liquefaction; beta3GnT activity improved 30%. This CPD-BmMNPV
      bacmid system provides rapid protein production in silkworms and can be used for
      the production of recombinant eukaryotic proteins without proteolytic
      degradation.

PMID- 17543395
TI  - Development of a whole blood intracellular cytokine staining assay for mapping
      CD4(+) and CD8(+) T-cell responses across the HIV-1 genome.
AB  - A whole blood peptide mapping intracellular cytokine staining (ICS) assay was
      developed that allows the direct comparison, at the individual peptide level, of
      CD4(+) and CD8(+) T-cell responses that span every encoded protein, in patients
      infected with HIV-1. Whole blood samples from HIV-1 infected patients were
      stimulated with overlapping synthetic peptides spanning nine subtype C HIV-1 gene
      regions (Gag, Pol, Nef, Env, Tat, Rev, Vif, Vpu, Vpr). Following stimulation and
      permeabilization, cells were stained with fluorochrome labelled antibodies to
      CD3, CD8 (CD4(+) cells were defined as CD8 negative cells), and IL-2 and IFN
      gamma. A total of 396 overlapping peptides were arranged in pools with a matrix
      design which allowed the identification of individual peptide responses from
      multiple pool responses. HIV-1 infected patients screened using this method
      showed a broad range of peptide responses across the entire HIV-1 genome with CD8
      T-cell responses being higher in frequency in magnitude than CD4(+) T-cell
      responses. The advantages of this whole blood ICS assay include the following:
      (1) the response to all potential HIV-1 epitopes across the genome can be
      examined, (2) the responding cell type can be monitored in the same reaction, and
      (3) considerably less blood is required than would be necessary if peripheral
      blood mononuclear cells (PBMC) were first isolated prior to peptide stimulation.

PMID- 17543398
TI  - Targeted depletion of a mitochondrial nucleotidyltransferase suggests the
      presence of multiple enzymes that polymerize mRNA 3' tails in Trypanosoma brucei
      mitochondria.
AB  - Polyadenylation plays an important role in regulating RNA stability in
      Trypanosoma brucei mitochondria. To date, little is known about the enzymes
      responsible for the addition of mRNA 3' tails in this system. In this study, we
      characterize a trypanosome homolog of the human mitochondrial poly(A) polymerase,
      which we term kPAP2. kPAP2 is mitochondrially localized and expressed in both
      bloodstream and procyclic form trypanosomes. Targeted gene depletion using RNAi
      showed that kPAP2 is not required for T. brucei growth in either bloodstream or
      procyclic life stages, nor is it essential for differentiation from bloodstream
      to procyclic form. We also demonstrate that steady state abundance of several
      mitochondrial RNAs was largely unaffected upon kPAP2 down-regulation.
      Interestingly, mRNA 3' tail analysis of several mRNAs from both life cycle stages
      in uninduced kPAP2 RNAi cells demonstrated that tail length and uridine content
      are both regulated in a transcript-specific manner. mRNA-specific tail lengths
      were maintained upon kPAP2 depletion. However, the percentage of uridine residues
      in 3' tails was increased, and conversely the percentage of adenosine residues
      was decreased, in a distinct subset of mRNAs when kPAP2 levels were down
      regulated. Thus, kPAP2 apparently contributes to the incorporation of adenosine
      residues in 3' tails of some, but not all, mitochondrial mRNAs. Together, these
      data suggest that multiple nucleotidyltransferases act on mitochondrial mRNA 3'
      ends, and that these enzymes are somewhat redundant and subject to complex
      regulation.

PMID- 17543399
TI  - A new Multi-PCR-SSCP assay for simultaneous detection of isoniazid and rifampin
      resistance in Mycobacterium tuberculosis.
AB  - Prompt detection of drug resistance in Mycobacterium tuberculosis is essential
      for effective control of tuberculosis (TB). We developed a Multi-PCR-SSCP method
      that detects more than 80% commonly observed isoniazid (INH) and rifampin (RIF)
      resistance M. tuberculosis in a single assay. The usefulness of the newly
      developed method was evaluated with 116 clinical isolates of M. tuberculosis.
      Distinct SSCP patterns were observed for different mutations and the correlation
      between Multi-PCR-SSCP results and DNA sequencing data was strong. Using the
      culture-based phenotypic drug susceptibility testing as a reference, the
      sensitivity of the newly developed Multi-PCR-SSCP assay was determined to be 80%
      and 81.8% for INH and RIF, respectively. The specificity of the assay was 100%
      and 92%, for INH and RIF, respectively. Multi-PCR-SSCP provides a rapid and
      potentially more cost-effective method of detecting multidrug-resistant TB.

PMID- 17543397
TI  - Selective breeding for infant rat separation-induced ultrasonic vocalizations:
      developmental precursors of passive and active coping styles.
AB  - Human depression and anxiety disorders show inherited biases across generations,
      as do antisocial disorders characterized by aggression. Each condition is
      preceded in children by behavioral inhibition or aggressive behavior,
      respectively, and both are characterized by separation anxiety disorders. In
      affected families, adults and children exhibit different forms of altered
      autonomic nervous system regulation and hypothalamic-pituitary-adrenal activity
      in response to stress. Because it is difficult to determine mechanisms accounting
      for these associations, animal studies are useful for studying the fundamental
      relationships between biological and behavioral traits. Pharmacologic and
      behavioral studies suggest that infant rat ultrasonic vocalizations (USV) are a
      measure of an early anxiety-like state related to separation anxiety. However, it
      was not known whether or not early ultrasound emissions in infant rats are
      markers for genetic risk for anxiety states later in life. To address these
      questions, we selectively bred two lines of rats based on high and low rates of
      USV to isolation at postnatal (P) 10 days of age. To our knowledge, ours is the
      only laboratory that has ever selectively bred on the basis of an infantile trait
      related to anxiety. The High and Low USV lines show two distinct sets of patterns
      of behavior, physiology and neurochemistry from infancy through adulthood. As
      adults High line rats demonstrate "anxious"/"depressed" phenotypes in behavior
      and autonomic nervous system (ANS) regulation to standard laboratory tests. In
      Lows, on the other hand, behavior and autonomic regulation are consistent with an
      "aggressive" phenotype. The High and Low USV lines are the first genetic animal
      models implicating long-term associations of contrasting "coping styles" with
      early attachment responses. They thus present a potentially powerful model for
      examining gene-environment interactions in the development of life-long affective
      regulation.

PMID- 17543400
TI  - Immunoglobulin cleavage by the streptococcal cysteine protease IdeS can be
      detected using protein G capture and mass spectrometry.
AB  - The immunoglobulin degrading enzyme of Streptococcus pyogenes, IdeS, is an
      unusual cysteine protease produced by group A streptococci for which the only
      known substrate is immunoglobulin G (IgG). To date, IdeS has not been found to
      cleave any of the known synthetic substrates that other cysteine proteases
      hydrolyse, thus making the development of an IdeS detection assay difficult.
      Furthermore, at high doses of substrate, product generation is inhibited
      potentially due to the need for a dimeric enzyme complex with IgG. In this study
      we have developed a mass spectral assay for IdeS activity based on the detection
      of an Mr approximately 25,300 Fc fragment that retains the ability to bind
      streptococcal protein G. Using this assay procedure, evidence for a multimeric
      enzyme-substrate complex was obtained as well as identifying isolated heavy
      chains as a non-substrate inhibitor of IdeS activity. Under appropriate
      experimental conditions the assay could be used to detect IdeS activity in
      bacterial culture media or in human plasma without a requirement for purified
      reactants. The availability of a rapid and sensitive assay for IdeS should
      facilitate the detailed biochemical characterization of this unusual bacterial
      cysteine protease.

PMID- 17543401
TI  - Development and evaluation of 50-mer oligonucleotide arrays for detecting
      microbial populations in Acid Mine Drainages and bioleaching systems.
AB  - To effectively monitor microbial populations in acidic environments and
      bioleaching systems, a comprehensive 50-mer-based oligonucleotide microarray was
      developed based on most of the known genes associated with the acidophiles. This
      array contained 1,072 probes in which there were 571 related to 16S rRNA and 501
      related to functional genes. The functional genes in the microarray were involved
      in carbon metabolism (158), nitrogen metabolism (72), sulfur metabolism (39),
      iron metabolism (68), DNA replication and repair (97), metal-resistance (27),
      membrane-relate gene (16), transposon (13) and IST sequence (11). Based on the
      results of microarray hybridizations, specificity tests with representative pure
      cultures indicated that the designed probes on the arrays appeared to be specific
      to their corresponding target genes. The detection limit was 5 ng of genomic DNA
      in the absence of background DNA. Strong linear relationships between the signal
      intensity and the target DNA were observed (r(2) approximately 0.98). Application
      of this type of the microarray to analyze the acidic environments and bioleaching
      systems demonstrated that the developed microarray appeared to be useful for
      profiling differences in microbial community structures of acidic environments
      and bioleaching systems. Our results indicate that this technology has potential
      as a specific, sensitive, and quantitative tool in revealing a comprehensive
      picture of the compositions of genes related with acidophilic microorganism and
      the microbial community in acidic environments and bioleaching systems, although
      more work is needed to improve.

PMID- 17543402
TI  - Hypoxia-imaging with (18)F-Misonidazole and PET: changes of kinetics during
      radiotherapy of head-and-neck cancer.
AB  - BACKGROUND AND PURPOSE: PET with (18)F-Misonidazole (FMISO-PET) is a non-invasive
      method for measuring tumor hypoxia. We analysed changes of FMISO-uptake during
      radiotherapy and their impact on patient outcome. MATERIALS AND METHODS: Fourteen
      patients with HNC underwent repeated FMISO-PET prior to radiotherapy and after
      30Gy. Dynamic and static PET-scans (2+4h p.i.) were acquired. FMISO-uptake was
      quantified by calculating standard uptake values (SUV) and tumor-muscle-ratios
      (TMR). Kinetic curve types representing tissue hypoxia were defined. Change of
      curve type was correlated with patient outcome. RESULTS: The mean SUV 4h p.i. and
      the TMR decreased significantly during radiotherapy. SUV decreased clearly in
      12/14 patients, and increased in 2 patients. TMR decreased in 11 patients, and
      increased in 3 patients. Prior to radiotherapy, three different shapes of kinetic
      curve types indicative for the degree of hypoxia could be defined in 12/14
      patients: (1) accumulation type (severe hypoxia (n=8)), (2) intermediate type
      (intermediate degree of hypoxia (n=3)), and (3) wash-out type (low degree of
      hypoxia (n=1)). Curve type changed towards a lower degree of hypoxia at 30Gy in
      all but 3 patients. In three patients curve type remained unchanged. CONCLUSIONS:
      The changes in tumor FMISO-uptake during radiotherapy indicate radio-induced
      reoxygenation.

PMID- 17543403
TI  - Lack of prognostic and predictive value of CA IX in radiotherapy of squamous cell
      carcinoma of the head and neck with known modifiable hypoxia: an evaluation of
      the DAHANCA 5 study.
AB  - BACKGROUND AND PURPOSE: CA IX is suggested to be an endogenous marker of hypoxia
      in tumours like squamous cell carcinomas of the head and neck (HNSCC). The aim of
      the present study was to investigate whether CA IX served as a prognostic factor
      for outcome in a large population of HNSCC and if CA IX was able to discriminate
      the tumours that did benefit from hypoxic modification with nimorazole. MATERIALS
      AND METHODS: Paraffin-embedded formalin-fixed pre-treatment tumour tissue was
      available from 320 of the 414 patients treated in the randomized DAHANCA 5
      protocol with primary radiotherapy+/-the hypoxic radiosensitizer nimorazole. CA
      IX was measured using immunohistochemistry and results were divided into four
      groups of CA IX expression: <1%, 1-10%, 10-30% and >30% of the tumour area with
      positive membrane staining. Locoregional control and disease-specific survival
      were used as endpoints. RESULTS: Expression of CA IX was not correlated to any of
      the tumour or patient characteristics investigated. Furthermore, CA IX did not
      serve as a prognostic marker in the total cohort as well as in the group of 150
      patients treated without nimorazole. Finally, no relation was found between the
      different expression levels of CA IX and the influence of nimorazole when
      locoregional control or disease-specific survival was used as endpoints.
      CONCLUSIONS: This is to date one of the largest studies of CA IX in HNSCC. The
      data suggest that CA IX have no prognostic or predictive potential in patients
      with cancer in the head and neck treated with conventional radiotherapy and
      concomitant nimorazole.

PMID- 17543404
TI  - Individual differences in cognitive reappraisal: experiential and physiological
      responses to an anger provocation.
AB  - Effective emotion regulation is widely seen as vital for healthy adaptation.
      There remains considerable uncertainty, however, as to what constitutes effective
      emotion regulation. One promising emotion regulation strategy is cognitive
      reappraisal, which involves reframing emotional events so as to decrease their
      emotional impact. This strategy is useful because it seems to enable individuals
      to down-regulate negative feelings without the physiological costs that are
      associated with other forms of emotion regulation. It remains unknown, however,
      whether individual differences in the use of reappraisal are associated with
      experiential and physiological responses to anger-inducing situations. To examine
      this question, individuals either high or low in reappraisal were made angry in
      the laboratory while emotion experience and cardiovascular responses were
      assessed. Results indicated that compared to low reappraisers, high reappraisers
      had a more adaptive profile of emotion experience and cardiovascular responding.
      Specifically, across baseline and provocation periods, high reappraisers reported
      less anger, less negative emotion, and more positive emotion, showed greater
      cardiac output and ventricular contractility, and lesser total peripheral
      resistance. These findings suggest that reappraisers are successful at down
      regulating negative emotions, even in the context of a potent negative emotion
      such as anger.

PMID- 17543405
TI  - Interoceptive sensitivity and emotion processing: an EEG study.
AB  - Theories of emotion consider the self-perception of visceral activity to play an
      important role in emotion. This study examined the relationship between
      interoceptive sensitivity and both the subjective emotional experience and the
      processing of emotional pictures. According to their results in a heartbeat
      detection task subjects were classified as good (N = 17) or poor (N = 20)
      heartbeat perceivers. Event-related potentials were recorded while subjects
      viewed pleasant, neutral and unpleasant pictures and SAM ratings were examined.
      Good heartbeat perceivers showed significantly greater P300 and slow wave
      amplitudes for emotional pictures at antero-inferior, medial and posterior
      electrode sites and experienced a greater arousal for emotional pictures compared
      to poor heartbeat perceivers. The heartbeat perception score correlated
      significantly positive both with emotional P300 and slow wave amplitudes as well
      as with the arousal ratings for emotional pictures. The results indicate that
      there is a significant and strong association between interoceptive sensitivity
      and the intensity of emotional experience as well as the central processing of
      emotional stimuli.

PMID- 17543406
TI  - Antimicrobial and safety aspects, and biotechnological potential of
      bacteriocinogenic enterococci isolated from mallard ducks (Anas platyrhynchos).
AB  - Samples from the intestinal content and carcasses of mallard ducks (Anas
      platyrhynchos) were evaluated for enterococci with antimicrobial activity,
      presence of genes coding bacteriocins and their expression, and potential
      virulence factors. Enterococcus faecalis comprised the largest enterococcal
      species with antagonistic activity followed by E. faecium, E. hirae, Enterococcus
      spp., and the non-enterococci. Although all E. faecalis isolates manifested a
      potent direct antimicrobial activity, no activity was detected in supernatants of
      most producer cultures. However, all E. faecium isolates showed antimicrobial
      activity in their supernatants and encoded bacteriocins, although the occurrence
      in the isolates of several enterocin genes did not always correlate with a higher
      antagonistic activity in supernatants. The efaAfm determinant was the only
      virulence gene detected in E. faecium, while E. faecalis showed a larger number
      of virulence determinants, and E. hirae did not carry any of the virulence genes
      examined. The rapid identification of genes coding described bacteriocins permits
      recognition of isolates that are potentially producers of novel bacteriocins.
      Purification of the antimicrobial activity of E. hirae DCH5 and Lactococcus
      garvieae DCC43 revealed unique chromatographic fragments after MALDI-TOF mass
      spectrometry analysis, suggesting the antagonistic peptides were purified to
      homogeneity. Bacteriocinogenic E. faecium and E. hirae isolates may be considered
      hygienic for production of bacteriocins, and potentially safe due to their low
      incidence of potential virulence genes and susceptibility to most clinically
      relevant antibiotics. However, the presence among the enterococci of E. faecalis
      strains with a potent antagonistic activity and multiple virulence factors,
      raises concerns regarding their potential pathogenicity to consumers.

PMID- 17543407
TI  - An on-line method for the reduction of fouling of spin-filters for animal cell
      perfusion cultures.
AB  - The main limitation in the use of spin-filters during perfusion cultures of
      animal cells was revealed to be filter fouling. This phenomenon involves cell
      sieve interactions as well as cell attachment to, and growth on, the filter
      surface. The cell attachment effect has been analysed in the present study during
      long-term perfusion simulations with CHO animal cells. It was demonstrated that
      at low filter acceleration, below 6.2 m/s2, a high perfusion rate of 25 cm/h
      induced rapid filter pore clogging within 3 days, whereas increasing the filter
      acceleration to 25 m/s2 increased filter longevity from 3 to 25 days, for filters
      with a pore size of 8.5 microm. Increasing the filter pore size to 14.5 microm
      improved filter longevity by 84% with less viable and dead cell deposits on the
      filter surface. However, it was demonstrated that filter longevity was not
      necessarily dependent on the amount of cell deposit on the filter surface. In the
      second part of this study, ultrasonic technology was used to reduce filter
      fouling. Filter vibration, induced by a piezo actuator, improved filter longevity
      by 113% during CHO cells perfusion cultures.

PMID- 17543408
TI  - Enzymatic synthesis of poly(hydroxyalkanoates) in ionic liquids.
AB  - Ring-opening polymerization of five lactones catalyzed by Candida antarctica
      lipase B in ionic liquids yielded poly(hydroxyalkanoates) of moderate molecular
      weights up to Mn=13,000. In the ionic liquid 1-butyl-3-methylimidazolium
      bis(trifluoromethane)-sulfonimide and with a low weight ratio of enzyme to
      lactone (1:100) we obtained polymers from beta-propiolactone, delta
      valerolactone, and epsilon-caprolactone with degrees of polymerization as high as
      170, 25, and 85, respectively; oligomers from beta-butyrolactone and gamma
      butyrolactone with degrees of polymerization of 5; and a copolymer of beta
      propiolactone and beta-butyrolactone with a degree of polymerization of 180.
      Water-immiscible ionic liquids were superior to water-miscible ionic liquids.
      Reducing the water content of the enzyme improved the degree of polymerization by
      as much as 50% for beta-propiolactone and epsilon-caprolactone.

PMID- 17543409
TI  - Studies on intracellular degradation of polyhydroxyalkanoic acid-polyethylene
      glycol copolymer accumulated by Azotobacter chroococcum MAL-201.
AB  - Azotobacter chroococcum MAL-201 accumulates poly(3-hydroxybutyric acid) [PHB]
      when grown in glucose containing nitrogen-free Stockdale medium. The same medium
      supplemented with valerate alone and valerate plus polyethylene glycol (PEG)
      leads to the accumulation of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) [PHBV]
      and PEG containing PHBV-PEG polymers, respectively. The intracellular degradation
      of these polymers as studied in carbon-free Stockdale medium showed a rapid
      degradation of PHB followed by PHBV, while it was least in case of PHBV-PEG. The
      rate of such degradation was 44.16, 26.4 and 17.0 mg h(-1)l(-1) for PHB, PHBV and
      PHBV-PEG, respectively. During the course of such of PHBV and PHBV-PEG
      degradation the 3HB mol% of polymers decreased significantly with increase of 3HV
      mol fraction, the EG mol% in PHBV-PEG, however, remained constant. After 50h of
      degradation the decrease in intrinsic viscosity and molecular mass of PHBV-PEG
      were 37.5 and 43.6%, respectively. These values appeared low compared to PHB and
      PHBV. Moreover, the increasing EG content of polymer retarded their extent of
      degradation. Presence of PEG, particularly of low molecular weight PEG was
      inhibitory to intracellular PHA depolymerise (i-PHA depolymerase) activity and
      the relative substrate specificity of the i-PHA depolymerase of MAL-201 appeared
      to be PHB > PHBV > PHBV-PEG.

PMID- 17543411
TI  - Biotechnological production of (R)-3-hydroxybutyric acid monomer.
AB  - The escalating problems regarding the treatment of plastic waste materials have
      led to development of biodegradable plastics. At present, a number of aliphatic
      polyesters; such as poly[(R)-3-hydroxybutyrate] (PHB), poly(l-lactide),
      polycaplolactone, poly(ethylene succinate) and poly(butylene succinate) have been
      developed. Among these aliphatic polyesters, PHB is one of the most attractive
      since it can undergo biodegradation at various environmental conditions and has
      properties similar to polypropylene. Although much effort has been made to
      produce PHB and its copolyesters from renewable resources or through microbial
      processes, their commercialization and widespread application are still not
      economically attractive compared to conventional non-biodegradable plastic.
      Moreover, wide application of PHB and its copolyesters as biodegradable plastic
      have not only been limited by the cost of production but also by their stinky
      smell during industrial processing. However, (R)-3-hydroxybutyric acid, a monomer
      of PHB has wide industrial and medical applications. (R)-3-hydroxybutyric acid
      can also serve as chiral precursor for synthesis of pure biodegradable PHB and
      its copolyesters. A number of options are available for production of (R)-3
      hydroxybutyric acid. This review discusses each of these options to assess the
      alternatives that exist for production of pure biodegradable PHB and its
      copolyesters with good properties.

PMID- 17543410
TI  - Application of enzymes, sodium tripolyphosphate and cation exchange resin for the
      release of extracellular polymeric substances from sewage sludge.
      Characterization of the extracted polysaccharides/glycoconjugates by a panel of
      lectins.
AB  - The study describes extraction of extracellular polymeric substances (EPS) from
      sewage sludge by applying enzymes and enzymes combined with sodium
      tripolyphosphate (STPP). Additionally, a systematic study of two non-enzymatic
      extraction agents is described. The assessment of the released products is made
      by colorimetrical methods and polysaccharides/glycoconjugates identification by
      the interaction with four immobilized lectins. Bio-sludge from Helsingborg
      (Sweden) and Damhusaen (Denmark) were used as two case studies for testing
      enzymatic extractability and thereby to make useful prediction of sludge bio
      digestibility. From Helsingborg sludge the enzymes extracted about 40% more of
      EPS than from Damhusaen. The polysaccharides/glycoconjugates in both sludges
      maintained the same level, and showed substantial different interaction motifs
      with lectins panel. Damhusaen enzymatic extracted EPS had an enhanced amount of
      suspended material that was post-hydrolysed by the use of polygalacturonase and
      lysozyme resulting in pectin like polymers and petiptidoglycans. Petiptidoglycan
      is a marker from bacterial cell debris. STPP and cation exchange resin (CER)
      released different quantities of EPS. The CER released
      polysaccharides/glycoconjugates had higher molecular weight and stronger affinity
      towards Concanavalin A than the one released by the action of STPP. Independent
      of the extraction conditions, STPP released elevated amounts of polyvalent
      cations and humic substances in contrast to the very low amounts of released by
      CER.

PMID- 17543413
TI  - Effect of pioglitazone therapy in lean type 1 diabetes mellitus.
AB  - OBJECTIVE: The beneficial effects of metformin in peripubertal adolescents and
      rosiglitazone in overweight type 1 diabetic subjects, though modest have been
      demonstrated. This study was designed to analyze the effect of pioglitazone as an
      adjunctive therapy in post-pubertal lean T1DM. PATIENTS AND METHODS: Sixty type 1
      diabetic subjects with duration of illness of a year or more with body mass index
      between 18 and 24.9 kg/m(2) were randomly assigned to receive either 30 mg
      pioglitazone or placebo once daily for 6 months. The study was double-blinded
      placebo controlled with 30 subjects in each group, matched for age, sex,
      anthropometric and metabolic parameters. At the end of the study period, plasma
      glucose levels, HbA(1c), lipids and insulin requirement were compared between the
      two groups. RESULTS: A significant improvement in post-prandial plasma glucose
      (PPPG) levels (9.1+/-1.7 and 8.4+/-1.3 mmol/L, p=0.002) and HbA(1c) (7.08+/-0.48
      and 6.86+/-0.45%, p=0.001) were observed in the pioglitazone treated group, but
      not in the placebo treated group (8.3+/-1.8 and 7.8+/-1.8 mmol/L, p=0.06 and
      HbA(1c) 7.3+/-0.37 and 7.24+/-0.33%, p=0.74, respectively). However, the mean
      decrease in PPPG and HbA(1c) levels between groups corrected for baseline values
      at the end of study was significant only for the later (HbA(1c) -0.22+/-0.29 and 
      0.06+/-0.49, p=0.03), while for the former, it got attenuated (PPPG -0.69+/-1.1
      and -0.48+/-1.36, p=0.68). There was no alteration in body weight, body mass
      index, insulin requirement, blood pressure and lipid profile in both the groups
      at the end of the study. CONCLUSION: Pioglitazone is modestly effective adjunct
      to insulin therapy in lean type 1 diabetic subjects. It improves post-prandial
      glucose levels and HbA(1c) without alterations in body weight and insulin
      requirement.

PMID- 17543414
TI  - Clinician reflections on promotion of healthy behaviors in primary care practice.
AB  - OBJECTIVE: Recommendations to use integrated models for health behavior change
      abound, however, the translation to practice has been poor. We used stimulated
      reflections of primary care physicians and nurse practitioners to generate
      insights about current practices and opportunities for changing how health
      behavior advice is addressed. METHOD: Twenty-one community practicing primary
      care clinicians invited to a nationally sponsored practice-based research network
      conference on promotion of healthy behaviors were asked to record aspects of
      health behaviors they addressed during a day of outpatient visits. In response to
      eight questions, clinicians reflected insights which were then analyzed by a
      multidisciplinary team to identify over-arching themes. RESULTS: Health behavior
      discussions are initiated and carried out predominantly by the clinician. These
      discussions occur primarily during health care maintenance visits or visits in
      which presenting complaints or chronic illnesses can be linked to health
      behaviors. Clinicians' reflections on viable opportunities for change include
      different modes of patient education materials such as web-based materials.
      Suprisingly infrequent were solutions outside of the clinical encounter or
      strategies that engage other staff or other community partners. CONCLUSION:
      Implementation of the integrated care model as an opportunity to enhance health
      promotion seems far from the current realities and future vision of even
      motivated network-based clinicians.

PMID- 17543415
TI  - Automatic detection of the breast border and nipple position on digital
      mammograms using genetic algorithm for asymmetry approach to detection of
      microcalcifications.
AB  - The presence of microcalcifications in breast tissue is one of the most incident
      signs considered by radiologist for an early diagnosis of breast cancer, which is
      one of the most common forms of cancer among women. In this paper, the Genetic
      Algorithm (GA) is proposed for automatic look at commonly prone area the breast
      border and nipple position to discover the suspicious regions on digital
      mammograms based on asymmetries between left and right breast image. The basic
      idea of the asymmetry approach is to scan left and right images are subtracted to
      extract the suspicious region. The proposed system consists of two steps: First,
      the mammogram images are enhanced using median filter, normalize the image, at
      the pectoral muscle region is excluding the border of the mammogram and comparing
      for both left and right images from the binary image. Further GA is applied to
      magnify the detected border. The figure of merit is calculated to evaluate
      whether the detected border is exact or not. And the nipple position is
      identified using GA. The some comparisons method is adopted for detection of
      suspected area. Second, using the border points and nipple position as the
      reference the mammogram images are aligned and subtracted to extract the
      suspicious region. The algorithms are tested on 114 abnormal digitized mammograms
      from Mammogram Image Analysis Society database.

PMID- 17543416
TI  - Solid lipid nanoparticles as a drug delivery system for peptides and proteins.
AB  - Solid lipid particulate systems such as solid lipid nanoparticles (SLN), lipid
      microparticles (LM) and lipospheres have been sought as alternative carriers for
      therapeutic peptides, proteins and antigens. The research work developed in the
      area confirms that under optimised conditions they can be produced to incorporate
      hydrophobic or hydrophilic proteins and seem to fulfil the requirements for an
      optimum particulate carrier system. Proteins and antigens intended for
      therapeutic purposes may be incorporated or adsorbed onto SLN, and further
      administered by parenteral routes or by alternative routes such as oral, nasal
      and pulmonary. Formulation in SLN confers improved protein stability, avoids
      proteolytic degradation, as well as sustained release of the incorporated
      molecules. Important peptides such as cyclosporine A, insulin, calcitonin and
      somatostatin have been incorporated into solid lipid particles and are currently
      under investigation. Several local or systemic therapeutic applications may be
      foreseen, such as immunisation with protein antigens, infectious disease
      treatment, chronic diseases and cancer therapy.

PMID- 17543417
TI  - Is there any relationship between obesity and mental flexibility in children?
AB  - Cognitive profiles of 12 schoolboys with obesity were compared with their peers
      with normal weight. For the cognitive assessment five clinical tasks were
      selected: digit span memory, Raven's progressive matrices (intelligence),
      semantic verbal fluency, D2 attention endurance and Wisconsin card sorting test.
      We found no differences in memory, intelligence and verbal fluency between the
      two groups. Children with obesity performed worse on D2 and Wisconsin tests.
      Correlations confirmed relationships between body weight, body mass index,
      attention and Wisconsin measured perseveration in set-shifting. This suggests
      that childhood obesity involves cognitive deficits in shifting and attention
      abilities.

PMID- 17543418
TI  - The excitotoxic effect of NMDA on human lymphocyte immune function.
AB  - N-Methyl-d-aspartate (NMDA)-activated glutamate receptors are expressed in
      lymphocytes, but their roles have not yet been defined. We show that incubation
      of human peripheral blood lymphocytes with NMDA resulted in increased
      intracellular calcium and reactive oxygen species (ROS) levels through effects on
      NMDA-activated glutamate receptors. In terms of ROS production, T cells were most
      affected, followed by NK cells, whereas B cell ROS levels were not increased. In
      unstimulated T and NK cells, interferon-gamma (IFN-gamma) production was
      unaffected by NMDA, whereas interleukin-2 stimulation of IFN-gamma production was
      significantly suppressed by NMDA. Simultaneous incubation of the cells with NMDA
      and IL-2 resulted in a dramatic increase in the amount of cells expressing the
      NR1 subunit of the NMDA-activated receptors. We conclude that NMDA-activated
      glutamate receptor activation, accompanied by the changes in intracellular
      calcium and ROS levels, may be involved in the modification of immune functions
      of human T and NK cells.

PMID- 17543419
TI  - Histone modifications in the brain.
AB  - Chromatin remodelling, including histone modifications has been recognized to
      play a central role in the regulation of gene expression. Histone modifications
      are mostly based on studies in cell culture systems in vitro. Recent evidence
      suggests that histone modifications are actively involved in activity-dependent
      neural plasticity via regulation of critical gene transcription necessary for the
      biological process in vivo. We have reviewed here the recent works studied on
      long-term memory formation, visual cortical plasticity during the critical period
      and drug-induced status epilepticus to elucidate a role for histone modifications
      in these biological processes. All of the studies indicate that chromatin
      structure, including histone modifications is highly dynamic within the nervous
      system and suggest the possibility that chromatin structure itself might be
      recruited as a target of plasticity-associated signal transduction mechanisms.

PMID- 17543420
TI  - Effect of nitroxyl on the hamster retinal nitridergic pathway.
AB  - There is a growing body of evidence on the role of nitric oxide (NO) in retinal
      physiology. Recently, interest has developed in the functional role of an
      alternative redox form of NO, namely nitroxyl (HNO/NO(-)), because it is formed
      by a number of diverse biochemical reactions. The aim of the present report was
      to comparatively analyze the effect of HNO and NO on the retinal nitridergic
      pathway in the golden hamster. For this purpose, sodium trioxodinitrate (Angeli's
      salt) and diethylammonium (Z)-1-(N,N-diethylamino)diazen-1-ium-1,2-diolate
      (DEA/NO) were used as HNO and NO releasers, respectively. Angeli's salt and
      DEA/NO significantly decreased nitric oxide synthase activity. In addition,
      Angeli's salt (but not DEA/NO) significantly decreased l-arginine uptake. DEA/NO
      significantly increased cGMP accumulation at low micromolar concentrations, while
      Angeli's salt affected this parameter with a threshold concentration of 200muM.
      Although Angeli's salt and DEA/NO significantly diminished reduced glutathione
      and protein thiol levels in a similar way, DEA/NO was significantly more
      effective than AS in increasing S-nitrosothiol levels. None of these compounds
      increased retinal lipid peroxidation. These results suggest that HNO could
      regulate the hamster retinal nitridergic pathway by acting through a mechanism
      that only partly overlaps with that involved in NO response.

PMID- 17543421
TI  - Metabolic correlates of clinical heterogeneity in questionable Alzheimer's
      disease.
AB  - Thirty-four subjects with questionable Alzheimer's disease (QAD) were included in
      a 3-year prospective study and underwent neuropsychological testing and
      measurement of brain metabolism using FDG-PET at entry. Seventeen patients (50%)
      did not convert to AD during the follow-up period. Compared to elderly controls
      of similar age, the cerebral activity of non-converters was reduced in the
      dorsolateral prefrontal cortex. Moreover, the variability of metabolism in the
      posterior cingulate cortex was related to their visuospatial memory performance,
      while disparity in parietal activity was related to their verbal memory
      performance. These results demonstrate the cerebral metabolic heterogeneity of
      patients with QAD. Initial functional images of converters showed that activity
      was already impaired in the posterior cingulate, lateral temporal cortex,
      anterior cingulate and orbitofrontal cortex. This metabolic pattern is consistent
      with a pre-dementia stage of AD, and highlights the fact that significant frontal
      metabolic involvement may be associated with impaired activity in posterior
      associative cortices in very early AD.

PMID- 17543423
TI  - [Potassium channels, genetic and acquired diseases].
AB  - INTRODUCTION: K(+) channels allow the passive and selective transport of K(+)
      ions through the membranes. They control K(+) homeostasis, neuronal and muscular
      excitabilities, and neurotransmitter and hormone release. EXEGESIS: K(+) channels
      are composed of pore-forming subunits associated with regulatory subunits. Many
      different K(+) channels have been identified. CONCLUSION: This diversity is
      stressed by the growing number of genetic and acquired diseases associated with
      these channels.

PMID- 17543422
TI  - Exaggerated sickness behavior and brain proinflammatory cytokine expression in
      aged mice in response to intracerebroventricular lipopolysaccharide.
AB  - Age-associated changes in glial reactivity may predispose individuals to
      exacerbated neuroinflammatory cytokine responses that are permissive to cognitive
      and behavioral complications. The purpose of this study was to determine if aging
      is associated with an exaggerated sickness response to central innate immune
      activation. Our results show that intracerebroventricular (i.c.v.) administration
      of lipopolysaccharide (LPS) caused a heightened proinflammatory cytokine response
      (IL-1beta, IL-6, and TNFalpha) in the cerebellum 2h post i.c.v. injection in aged
      mice compared to adults. This amplified inflammatory profile was consistent with
      a brain region-dependent increase in reactive glial markers (MHC class II, TLR2
      and TLR4). Moreover, LPS caused a prolonged sickness behavior response in aged
      mice that was paralleled by a protracted expression of brain cytokines in the
      cerebellum and hippocampus. Finally, central LPS injection caused amplified and
      prolonged IL-6 levels at the periphery of aged mice. Collectively, these data
      establish that activation of the central innate immune system leads to
      exacerbated neuroinflammation and prolonged sickness behavior in aged as compared
      to adult mice.

PMID- 17543424
TI  - [Interleukin 13 and interleukin 13 receptor involvement in systemic sclerosis].
AB  - PURPOSE: Interleukin 13 is an immunoregulatory cytokine predominantly secreted by
      activated Th2 cells. It has similar functions with interleukin 4 and they share a
      common receptor. However, unlike interleukin 4, l'interleukin 13 does not appear
      to be important in the initial differentiation of CD4 T into Th2-type cells, but
      rather appears to be necessary in the effector phase of inflammation and
      fibrosis. This cytokine has been involved in recent works in allergic
      inflammation and in some fibrotic diseases leading to a scientific interest to
      analysis the role of interleukin 13 in systemic sclerosis (scleroderma). MAIN
      POINTS: Systemic sclerosis is an autoimmune disease characterized by vascular
      alteration and skin and visceral fibrosis. A genetic background associated with
      susceptibility is supposed. Knowing the profibrogenic properties of interleukin
      13, we asked if polymorphisms located in interleukin 13 and interleukin 13
      receptor genes could be associated with systemic sclerosis. We observed
      significant associations between IL13 and IL13RA2 gene polymorphisms and the
      disease, particularly the cutaneous diffuse form of the disease. PERSPECTIVES AND
      PROJECTS: Results concerning the involvement of interleukin 13 pathway in
      systemic sclerosis need to be confirmed on another larger population. Functional
      studies will be done to explain the effect of these associations. We feel that
      IL13/IL13R pathway is interesting as immunomodulation with the interleukin 13
      receptor inhibitor is possible in therapy.

PMID- 17543425
TI  - Human metapneumovirus: enhanced pulmonary disease in cotton rats immunized with
      formalin-inactivated virus vaccine and challenged.
AB  - Cotton rats (Sigmodon hispidus) are susceptible to the recently discovered human
      metapneumovirus (hMPV), an agent closely related to human respiratory syncytial
      virus. Since certain respiratory syncytial virus vaccines can induce enhanced
      disease upon viral challenge, we have done similar experiments with hMPV in
      cotton rats. Young adult cotton rats were vaccinated with a formalin-inactivated
      preparation of hMPV strain C-85473, or with a mock preparation of the vaccine on
      day 0 and again on day 28. All animals were challenged intranasally on day 49
      with 10(7) TCID50 of the same hMPV strain. Animals were sacrificed on days 4, 7,
      and 10 post-challenge and lungs were removed for viral quantitation,
      histopathology, and cytokine mRNA expression analysis (interferon-gamma (IFN
      gamma) and interleukin-4 (IL-4)). Although the vaccinated animals showed almost
      complete protection from viral replication in the lungs (<10(2.0) TCID50 per
      gram), there was a dramatic increase in the lung pathology, particularly the
      interstitial pneumonitis and alveolitis with elevated serum neutralizing antibody
      titer prior to challenge. Cytokine profiles were distinctive from those observed
      during primary infection and re-infection. The data raise safety concerns for
      hMPV vaccine preparations.

PMID- 17543426
TI  - Missed opportunities to vaccinate a cohort of hospitalised elderly with
      pneumococcal and influenza vaccines.
AB  - This study examines missed opportunities for recommended influenza vaccine and 23
      valent pneumococcal vaccine (23vPPV) among hospitalised elderly persons. 4772
      inpatients aged > or = 65 years (cases of pneumonia and frequency-matched
      randomly selected cohort subjects) participated from two large tertiary
      Australian hospitals. For subjects unvaccinated with influenza vaccine (past
      year), 1110/1115 (99.6%) had visited either a doctor (99.4%, mean 11.2 visits) or
      the same hospital (52.0%, mean 1.5 visits). For those unvaccinated with 23vPPV
      (past 5 years), 1809/1813 (99.8%) had visited either a doctor (99.7%, mean 11.2
      visits) or the same hospital (51.5%, mean 1.5 times) in the past year; 71% had
      been admitted to the same hospital in the past 5 years (mean 3.4 times). 2.3% of
      all subjects had vaccination status recorded. No unvaccinated subject was
      vaccinated during admission, despite approximately 40% reporting acceptability of
      vaccination if offered. Previous hospitalisation was a risk factor for being
      unvaccinated. Barriers to implementation of current vaccination policy in the
      hospital setting require formal evaluation in Australia.

PMID- 17543427
TI  - A fusogenic peptide expressed on the surface of Salmonella enterica elicits CTL
      responses to a dengue virus epitope.
AB  - Attenuated Salmonella strains are used widely as live carriers of antigens
      because they elicit both mucosal and systemic immunity against passenger
      antigens. However, they generally evoke poor cytotoxic T cell (CTL) responses
      because Salmonella resides within vacuolar compartments and the passenger
      antigens must travel to the cytosol and be processed through the MHC class I
      dependent pathway to simulate CTLs. To address this problem, we designed a fusion
      protein to destabilize the phagosome membrane and allow a dengue epitope to reach
      the cytosol. The fusion protein was displayed on the bacterial surface of
      Salmonella enterica serovar Typhimurium SL3261 through the beta domain of the
      autotransporter MisL. The passenger alpha domain contained, from the N-terminus,
      a fusogenic sequence, the NS3 protein 298-306-amino acid CTL epitope from the
      dengue virus type 2, a molecular tag, and a recognition site for the protease
      OmpT to release it to the milieu. Display of the fusion protein on the bacterial
      surface was demonstrated by IFA and flow cytometry using antibodies against the
      molecular tag. Cleavage of the fusogenic protein-dengue peptide was demonstrated
      by flow cytometry using OmpT+ Escherichia coli strains. The recombinant
      Salmonella strains displaying the fusogenic-dengue peptide were able to lyse
      erythrocytes, induced specific proliferative responses, and elicited CTL
      responses. These results suggest that the recombinant fusion proteins containing
      fusogenic sequences provide a promising system to induce CTLs by live vector
      vaccines.

PMID- 17543428
TI  - Survey of poliovirus antibodies during the final stage of polio eradication in
      Egypt.
AB  - BACKGROUND: Egypt provides ideal conditions for poliovirus (PV) transmission
      (high population density, high contact rates and low sanitation and hygiene in
      some areas). Despite excellent program performance, wild poliovirus type 1 (PV1)
      continue to circulate in 2004. To investigate potential causes for the
      persistence, we conducted a serological study. METHODS: Seroprevalence surveys
      were conducted in "polio-endemic" regions (Greater Cairo and Upper Egypt) and in
      one control region (Lower Egypt) in December 2004. Sera collected from infants
      aged 6-11 months were tested for antibodies to poliovirus by neutralization
      assay. RESULTS: A total of 973 subjects were tested. Seroprevalence to PV type 1
      (PV1), PV type 2 (PV2) and PV type 3 (PV3) was 99, 99 and 91%, respectively.
      Significant variation in PV3 seroprevalence was found (range: 76-100%). Region,
      density, maternal education, socioeconomic status (SES), stunting and diarrhea
      were significant risk factors for lower seroprevalence in the univariate
      analysis. CONCLUSIONS: Our study suggested that uniformly high immunity levels
      (>96%) were required to interrupt PV1 transmission in the last remaining
      reservoirs (last PV1 was isolated in mid-January 2005 in Egypt). It further
      suggests substantial regional differences in OPV immunogenicity, with rural areas
      and low SES achieving the lowest seroprevalence to PV3.

PMID- 17543429
TI  - Imject Alum is not aluminum hydroxide adjuvant or aluminum phosphate adjuvant.

PMID- 17543430
TI  - Application of ICP-QMS for the determination of plutonium in environmental
      samples for safeguards purposes.
AB  - Aiming to determine the plutonium amount as well as its isotopic composition, in
      particular, in swipe samples for safeguards purposes, an analytical method was
      developed with a plutonium separation step based on extraction chromatography
      using 2 cm TEVA columns and detection with quadrupole ICP-MS applying an ultra
      sonic nebulizer coupled with membrane desolvation system. The method was
      successfully applied to New Brunswick plutonium certified reference materials as
      well as to Lawrence Livermore National Laboratory round robin samples, based on
      the round robin samples provided by the Institute for Reference Materials and
      Measurements (Belgium), as part of the Regular European Interlaboratory
      Measurement Evaluation Programme (REIMEP), campaign 16 (isotopic abundances of
      plutonium in plutonium nitrate samples), with a total plutonium amount between 1
      and 0.25 ng per sample. After the introduction of an additional separation step,
      it was also possible to carry out precise and accurate total plutonium,
      (240)Pu/(239)Pu, (241)Pu/(239)Pu and (242)Pu/(239)Pu atom ratios determination in
      sediment sample showing its applicability to environmental samples in general,
      reaching a detection limit equivalent to 5 mBq(239)Pu kg(-1).

PMID- 17543431
TI  - The use of folic acid and other vitamins before and during pregnancy in a group
      of women in Melbourne, Australia.
AB  - OBJECTIVE: to explore the use of folic acid and other vitamin supplements before
      and during pregnancy, including type, dosage and form; who recommended supplement
      use and for what reason; and women's understanding of why they took folic acid.
      DESIGN: cross-sectional survey. SETTING: a public tertiary referral hospital in
      Melbourne, Australia. PARTICIPANTS: consecutive pregnant women at 36-38-weeks
      gestation completed a self-administered survey (available in English, Cantonese,
      Vietnamese, Turkish and Arabic). MEASUREMENTS: a structured questionnaire was
      used. Descriptive statistics are presented, with stratified and regression
      analyses to compare sub-groups. FINDINGS: of 705 eligible women, 588 (83%) agreed
      to participate. Of these, 88 (15%) completed the questionnaire in a language
      other than English. Twenty-nine per cent (168/588) of women took pre-pregnancy
      folic acid supplements. Only 23% reported taking a folic acid supplement for at
      least 4 weeks before pregnancy. During pregnancy, 79% of women took folic acid,
      most of whom commenced before 13 weeks. Other vitamin supplements taken during
      pregnancy were iron (52%), calcium (24%), Vitamin B6 (14%), pregnancy
      multivitamins (35%) and zinc (7%). Only 8% took no supplements at all in
      pregnancy. Factors associated with an increased risk of not taking folic acid
      were income < or =$30,000 (AUD) (adjusted odds ratio (OR) 2.85, 95% CI 1.84,
      4.40), smoking during pregnancy (adjusted OR 2.3, 95% CI 1.26, 4.48) and having
      other than a first baby (adjusted OR 1.89, 95% CI 1.22, 2.93). KEY CONCLUSIONS:
      uptake of folic acid supplementation in the periconceptional period was well
      below the target that all women planning pregnancy consume 0.4-0.5mg of folate
      per day. Less than one-third of this sample took a pre-pregnancy folic acid
      supplement, with differences in uptake by group. A large proportion of
      respondents also took a range of other vitamin supplements during pregnancy.
      IMPLICATIONS FOR PRACTICE: it is important to target women who are less likely to
      take periconceptional folic acid as well as to increase awareness among women of
      childbearing age in general.

PMID- 17543432
TI  - Metal concentrations and mobility in marine sediment and groundwater in coastal
      reclamation areas: a case study in Shenzhen, China.
AB  - The concentrations of metals in the buried marine sediment and groundwater were
      differently affected by land reclamation. Nine metals (V, Cr, Mn, Co, Ni, Cu, Zn,
      Cd and Pb) in sediment and coastal groundwater from reclamation areas in Shenzhen
      were examined. The gradually decreased concentrations (V, Cr, Mn, Ni, Cu, Zn) in
      sediment and relatively higher concentrations (V, Cr, Mn, Co, Ni, Cu and Cd) in
      groundwater within reclamation areas were observed. The increase of V, Cr, Mn,
      Ni, Cu and Cd concentrations in groundwater within reclamation areas subsequently
      after land reclamation should be resulted from the mobilization of these metals
      accumulated in the sediment. These metals appear to be easily mobilized from
      solid phase to solution phase after reclamation. The physico-chemical changes
      such as reduction in pH and salinity in water environment induced by land
      reclamation appear to be responsible for metal mobility in the sediment
      groundwater system.

PMID- 17543433
TI  - Isonychia spp. and macroinvertebrate community responses to stressors in streams
      utilizing the benthic in situ toxicity identification evaluation (BiTIE) method.
AB  - Exposures of caged organisms in situ have proven to be a useful way to improve
      exposure realism and link to stressor effects in aquatic assessments of hazard or
      risk. A novel cage system, the benthic in situ toxicity identification evaluation
      (BiTIE), was developed for benthic macroinvertebrates (surrogate species,
      resident populations and communities) to separate low and high flow effects, and
      major chemical classes of stressors in streams. Three resin types were used to
      separate the chemical stressors in the streams Honey Creek and Little
      Beavercreek, Ohio, USA: Dowex Optipore (non-polar organics), zeolite (ammonia),
      and polywool (control). Isonychia spp. sensitivity was compared to Chironomus
      tentans, and no significant differences were found (p>0.05). Isonychia spp.
      growth (length) showed a stressor response in the zeolite treatments, and
      community testing revealed improved metric responses in the Dowex treatments. The
      BiTIE chamber system demonstrated stressor-response relationships using sublethal
      and multimetric endpoints.

PMID- 17543434
TI  - Evaluating emerging issues in epidemiology.
AB  - Industry and government institutions need a credible approach for evaluating and
      responding to emerging public health issues. Representatives of industry,
      government, and academia met under the auspices of the International Life
      Sciences Institute's Health and Environmental Sciences Institute (HESI) to
      develop successful strategies for dealing with emerging issues based on
      historical case studies. The case studies chosen for evaluation were (1) tampon
      use and toxic shock syndrome; (2) hazardous waste and childhood cancer risk in
      Toms River, New Jersey; (3) fenfluramine and phentermine use and valvular heart
      disease; (4) silicone breast implants and cancer and auto-immune disease; and (5)
      progestational drugs and birth defects. We identified eight lessons from these
      case studies. Foremost, we recommend that public and private institutions not
      defer action until an issue is scientifically resolved and stress that
      cooperation among issue stakeholders is critical for effective issue resolution.
      We suggest establishing a research program as an effective way to assure that
      good science is included in resolution of the issue. We further recommend
      frequent and timely communication with all stakeholders, and the development of
      research approaches to fill gaps when the scientific data on an issue are
      limited.

PMID- 17543435
TI  - Aqueous and hydroalcoholic extracts of Black Maca (Lepidium meyenii) improve
      scopolamine-induced memory impairment in mice.
AB  - Lepidium meyenii Walp. (Brassicaceae), known as Maca, is a Peruvian hypocotyl
      growing exclusively between 4,000 and 4,500 m altitude in the central Peruvian
      Andes, particularly in Junin plateau. Previously, Black variety of Maca showed to
      be more beneficial than other varieties of Maca on learning and memory in
      ovariectomized mice on the water finding test. The present study aimed to test
      two different doses of aqueous (0.50 and 2.00 g/kg) and hydroalcoholic (0.25 and
      1.00 g/kg) extracts of Black Maca administered for 35 days on memory impairment
      induced by scopolamine (1mg/kg body weight i.p.) in male mice. Memory and
      learning were evaluated using the water Morris maze and the step-down avoidance
      test. Brain acetylcholinesterase (AChE) and monoamine oxidase (MAO) activities in
      brain were also determined. Both extracts of Black Maca significantly ameliorated
      the scopolamine-induced memory impairment as measured in both the water Morris
      maze and the step-down avoidance tests. Black Maca extracts inhibited AChE
      activity, whereas MAO activity was not affected. These results indicate that
      Black Maca improves scopolamine-induced memory deficits.

PMID- 17543436
TI  - Epithelial transport of deoxynivalenol: involvement of human P-glycoprotein
      (ABCB1) and multidrug resistance-associated protein 2 (ABCC2).
AB  - Deoxynivalenol (DON) is a major mycotoxic contaminant of cereal grains in Europe
      and North America. Human and animal contamination occurs mainly orally, and the
      toxin must traverse the intestinal epithelial barrier before inducing potential
      health effects. This study investigates the mechanisms of DON transepithelial
      transfer. Investigations using the human intestinal Caco-2 cell line showed a
      basal-to-apical polarized transport of the toxin. Both apical-basolateral (AP-BL)
      and basolateral-apical (BL-AP) transfers were time- and concentration-dependent,
      and not saturable between 5 and 30 microM DON. Arrhenius plot analysis revealed
      that transfer of 10 microM DON was temperature-dependent, with apparent
      activation energy E(a)=3.2 kcal mol(-1) in the AP-BL direction, and E(a)=10.4
      kcal mol(-1) in the BL-AP direction. Intracellular DON accumulation was increased
      and DON efflux was decreased by ATP depletion, by P-glycoprotein inhibitor
      valspodar and by MRP2 inhibitor MK571, but not by BCRP inhibitor Ko143.
      Intracellular DON accumulation was then investigated using epithelial cell lines
      transfected with human P-glycoprotein or MRP2. This accumulation was decreased in
      LLCPK1-MDR1 and MDCKII-MRP2 cells, compared to wild-type cells, and the decrease
      could be reversed by valspodar or MK571. Taken together, these results suggest
      that DON is a substrate for both P-glycoprotein and MRP2.

PMID- 17543437
TI  - Glutamine inhibits over-expression of pro-inflammatory genes and down-regulates
      the nuclear factor kappaB pathway in an experimental model of colitis in the rat.
AB  - We investigated the effects of glutamine on markers of oxidative stress, nuclear
      factor kappaB (NF-kappaB) activation, and pro-inflammatory mediators in a rat
      model of experimental colitis induced by intracolonic administration of 7% acetic
      acid. Glutamine (25 mg/kg) was given by rectal route 48 and 24h before acetic
      acid instillation. Glutamine significantly reduced gross damage and
      histopathological scores, and partially prevented the decrease of anal pressure
      observed in the animals receiving acetic acid. Increases in the cytosolic
      concentration of TBARS and hydroperoxide-initiated chemiluminescence were
      significantly prevented in glutamine-treated animals. Acetic acid instillation
      induced a marked increase of the NF-kappaB p65 subunit expression in the nucleus
      and resulted in significant changes in the cytosolic protein level of IkappaB
      kinases (IKKalpha and IKKbeta) and the non-phosphorylated form of the inhibitor
      IkappaBalpha. Protein levels of inducible nitric oxide synthase (iNOS) and
      cyclooxygenase-2 (COX-2) were significantly increased. All these effects were
      partially prevented by administration of glutamine. It is concluded that the anti
      inflammatory activity of glutamine in a rat model of acetic acid-induced colitis
      may be mediated, at least in part, by inhibition of the expression of certain pro
      inflammatory mediators which are regulated by the oxidative stress-sensitive NF
      kappaB signalling pathway.

PMID- 17543438
TI  - An antisense oligonucleotide to HSP47 inhibits paraquat-induced pulmonary
      fibrosis in rats.
AB  - The most common cause of death from poisoning by the widely used, but highly
      toxic herbicide paraquat is respiratory failure from pulmonary fibrosis, which
      develops through pathological overproduction of extracellular matrix proteins
      such as the collagens. Heat shock protein (HSP47) is a collagen-specific
      molecular chaperone that assists in the posttranslational modifications of
      procollagens during collagen biosynthesis. We investigated whether treatment with
      an HSP47-antisense oligonucleotide would inhibit paraquat-induced pulmonary
      fibrosis in Wistar rats. Rats randomized into three groups (control, paraquat,
      and paraquat+antisense). Paraquat (20 mg/kg/day) (n=16) or a saline control
      (n=10) was administered to groups of Wistar rats. Intratracheal administration of
      the antisense oligonucleotide (100 nmol/kg in saline) was performed after the
      initial paraquat treatment (n=16). Treatment with paraquat alone induced
      pulmonary fibrosis in the entire group, while treatment with the antisense
      oligonucleotide alone did not produce any substantial change in lung histology.
      Administration of antisense oligonucleotides produced a substantial reduction in
      paraquat-induced pulmonary fibrosis. An immunoblot analysis confirmed that the
      HSP47-antisense oligonucleotide inhibited HSP47 production. These findings
      indicate that the HSP47-antisense oligonucleotide inhibited paraquat-induced
      pulmonary fibrosis and pneumopathy in rats.

PMID- 17543439
TI  - Appraisal of formulas for stresses in bilayered dental ceramics subjected to
      biaxial moment loading.
AB  - OBJECTIVES: The purpose of this study was to compare three existing sets of
      formulas predicting stresses in a thin circular plate subjected to biaxial moment
      loading, such that limitations for each set of formulas could be understood.
      These formulas include American Society for Testing and Materials (ASTM) formulas
      for monolayered plates, Roark's formulas for bilayered plates, and Hsueh et al.'s
      formulas for multilayered plates. METHODS: The three sets of formulas were
      summarized and appraised. Biaxial moment loading is generally achieved using
      biaxial flexure tests, and the plate is placed on a support ring and loaded in
      the central region. While both ASTM and Hsueh et al.'s formulas predict stresses
      through the thickness of the plate, Roark's formulas predict stresses only on the
      top and the bottom surfaces of the plate. Also, a simply supported plate at its
      edge is considered in Roark's formulas. We modified Roark's formulas to include
      the overhang region of the plate to more closely simulate the actual loading
      configuration. Then, the accuracy of formulas was examined by comparing with
      finite element results of monolayered and bilayered plates subjected to ring-on
      ring loading. RESULTS: Monolayer is a special case of bilayer, and both monolayer
      and bilayer are special cases of multilayer. For monolayered plates, ASTM and
      Hsueh et al.'s formulas are identical, and both are in excellent agreement with
      finite element results. For bilayered plates, Hsueh et al.'s formulas are in
      excellent agreement with finite element results. For both monolayered and
      bilayered plates, Roark's formulas deviate from finite element results while the
      modified Roark's formulas are accurate. CONCLUSIONS: Roark's formulas for
      evaluating the biaxial strength of bilayered dental ceramics will result in
      errors in predicted stresses which depend on the size of the overhang region of
      the plate in the actual loading configuration. Also, Roark's formulas are limited
      to predicting stresses on the top and the bottom surfaces of the plate. On the
      other hand, Hsueh et al.'s formulas are for multilayered plates and predict
      stresses through the plate thickness.

PMID- 17543440
TI  - Phenytoin but not valproate directly affected in vitro trophoblast
      differentiation.
AB  - OBJECTIVE: Epilepsy has been associated with poor obstetric outcomes that could
      be the result of the epilepsy itself or a direct effect of anti-epileptic
      medication on placentation. The aim of this study was to investigate any direct
      effect of anti-epileptic drugs on an established, in vitro bioassay of
      trophoblast differentiation. STUDY DESIGN: Primary extravillous trophoblast cells
      were cultured in the presence of phenytoin and sodium valproate at a range of
      concentrations with appropriate solvent controls. The formation of multinuclear
      giant cells was used as a marker of trophoblast differentiation. RESULTS:
      Phenytoin inhibited giant multinuclear cell formation in a dose-dependent manner;
      in contrast sodium valproate had no effect (p=0.011). CONCLUSIONS: This study
      found that two anti-epileptic medications induced different effects on an in
      vitro trophoblast bioassay, suggesting that further research should be aimed at
      elucidating which anti-epileptic medication is most suitable for pregnant women.

PMID- 17543441
TI  - Integration host factor alters LacI-induced DNA looping.
AB  - The integration host factor protein of Escherichia coli, which sharply bends DNA
      at specific sites and non-specifically compacts the bacterial genome, can also
      alter looping of DNA in an artificial system based on the lactose repressor
      protein of E. coli. In single molecule experiments, we show that both specific
      bending and non-specific compaction alter LacI-mediated looping of DNA. Our
      results highlight the subtle regulatory roles that proteins, which confer
      structure upon DNA, might have in controlling DNA transcription and other
      processes in which the conformation of DNA determines the binding and activity of
      processive enzymes.

PMID- 17543442
TI  - Molecular characterization of two sea bass gonadotropin receptors: cDNA cloning,
      expression analysis, and functional activity.
AB  - The follicle-stimulating hormone (FSH) and the luteinizing hormone (LH) play
      central roles in vertebrate reproduction. They act through their cognate
      receptors to stimulate testicular and ovarian functions. The present study
      reports the cloning and characterization of two sea bass (Dicentrarchus labrax)
      cDNAs encoding a FSH receptor (sbsFSHR) and a LH receptor (sbsLHR). The mature
      proteins display typical features of the glycoprotein hormone receptor family
      members, but the sbsFSHR also contains some remarkable differences when compared
      with other fish or mammalian FSHRs. Among them, a distinct extracellular N
      terminal cysteine domain as regards to its length and cysteine number, and the
      presence of an extra leucine-rich repeat. Expression analysis revealed that the
      sbsFSHR is exclusively expressed in gonadal tissues, specifically in the
      follicular wall of previtellogenic and early-vitellogenic follicles. On the
      contrary, sbsLHR mRNA was found to be widely distributed in sea bass somatic
      tissues. When stably expressed in mammalian cell lines, sbsFSHR was specifically
      stimulated by bovine FSH, while sbsLHR was activated by both bovine LH and FSH.
      Nevertheless, specific stimulation of the sbsLHR was observed when recombinant
      sea bass gonadotropins were used. The isolation of a FSHR and a LHR in sea bass
      opens new ways to study gonadotropin action in this species.

PMID- 17543443
TI  - Diminution of basal ganglia dopaminergic function may play an important role in
      the generation of akinetic mutism in a patient with anterior cerebral arterial
      infarct.
AB  - We report the clinical features and dopamine transporter [2-[[2-[[[3-(4
      chlorophenyl)-8-methyl-8-azabicyclo[3.2.1]oct-2-yl]methyl](2
      mercaptoethyl)amino]ethyl]amino]ethanethiolato(3-)-N2,N20,S2,S20]oxo-[1R-(exo
      exo)]-[99mTc] technetium([99mTc]TRODAT-1) image finding in an 86-year-old woman
      with akinetic mutism due to infarction of bilateral anterior cerebral arterial
      territories. TRODAT-1 is a cocaine analogue that can be labeled with technetium
      99m and bound to the dopamine transporter (DAT) site. It reflects primarily the
      integrity of presynaptic dopamine neuron terminals. With the evolution of the
      clinical features, the TRODAT SPECT images change from bilateral diminution of
      radioactivity uptake at the 81st-day check point to normal pattern at the 6-month
      one when the akinetic mute manifestations were nearly gone. This novel
      illustration suggests that the akinetic mutism caused by anterior cerebral
      arterial infarct is closely linked to the perturbation of the subcortical
      dopaminergic system. And the amelioration of the clinical features concordantly
      evolved with the restoration of the dopaminergic function.

PMID- 17543444
TI  - Tumor cells from ultrasonic aspirations of glioblastomas migrate and form spheres
      with radial outgrowth.
AB  - Studies of primary cells from malignant brain tumors such as glioblastomas are
      limited by the small size of surgically resected specimens. However,
      glioblastomas are also frequently debulked via ultrasonic aspiration. In this
      study, we examined the functional competence and growth of their aspirated cells.
      Cells from minced tissue and aspirations were comparable in migration, formation
      of pseudopodia, development of cellular spheres with radial outgrowth, and
      neuroectodermal features. Cultures were maintained for more than six weeks
      without fibroblastic overgrowth. Our observations show that ultrasonically
      aspirated specimens contain cells useful for studies of tumor migration and
      growth of tumorspheres.

PMID- 17543445
TI  - Ultrasound assisted destruction of estrogen hormones in aqueous solution: effect
      of power density, power intensity and reactor configuration.
AB  - There are many reports documenting the adverse effects, such as feminization of
      fish, of estrogen hormones in the environment. One of the major sources of these
      compounds is from municipal wastewater effluents. The biological processes at
      municipal wastewater treatment plants cannot completely remove these compounds.
      This paper discusses the use of ultrasound to destroy estrogen compounds in
      water. The study examines the effect of ultrasound power density and power
      intensity on the destruction of various estrogen compounds which include: 17alpha
      estradiol, 17beta-estradiol, estrone, estriol, equilin, 17alpha-dihydroequilin,
      17alpha-ethinyl estradiol and norgestrel. These tests were conducted in single
      component batch and flow through reactors using 0.6, 2 and 4kW ultrasound
      sources. The sonolysis process produced 80-90% destruction of individual
      estrogens at initial concentration of 10microg/L within 40-60min of contact time.
      First order rate constants for the individual compounds under different
      conditions are presented. The estrogen degradation rates increase with increase
      in power intensity. However, the energy efficiency of the reactor was higher at
      lower power density. The 4kW ultrasound reactor was more energy efficient
      compared to the 0.6 and 2kW sonicators.

PMID- 17543446
TI  - Oil palm ash as partial replacement of cement for solidification/stabilization of
      nickel hydroxide sludge.
AB  - In this study, solidification/stabilization (S/S) of nickel hydroxide sludge
      using ordinary Portland cement (OPC) and oil palm ash (OPA) was carried out. The
      effects of increased substitution of OPA wt% in the S/S mix designs on the
      treated samples' physical and chemical characteristics were investigated. The
      physical characteristics studied were unconfined compressive strength (UCS) and
      changes in crystalline phases while chemical characteristics studied were
      leachability of nickel and leachate pH. Results indicated the optimum mix design
      for S/S of nickel hydroxide sludge using both OPC and OPA at B/S(d)=1 in terms of
      cost-effectiveness and treatment efficiency was 15 wt% OPA, 35 wt% OPC and 50 wt%
      sludge. The sufficient UCS and low leached nickel concentrations shown for this
      mix design indicate the viability of using OPA as substitute of OPC as it can
      significantly reduce cost normally incurred by usage of high amounts of OPC.

PMID- 17543447
TI  - On the individual exposure from airborne hazardous releases: the effect of
      atmospheric turbulence.
AB  - One of the key problems in coping with deliberate or accidental atmospheric
      releases is the ability to reliably predict the individual exposure during the
      event. Furthermore, for the implementation of countermeasures, it is essential to
      predict the maximum expected dosage and the exposure time within which the dosage
      exceeds certain health limits. Current state of the art methods, which are based
      on the concentration cumulative distribution function (cdf) and require the
      knowledge of the concentration variance and the intermittency factor, have
      certain limitations especially when the exposure time becomes comparable with the
      peak spectral time. The proposed method aims at estimating maximum dosage as a
      function of the exposure time, mean concentration and the turbulence integral
      time scale. It is much simpler than the cdf models and it poses no restrictions
      on the exposure time length. One of the important consequences is that it can
      broaden the capability of the ensemble average computational models to estimate
      maximum dosage for any exposure time. The method has been tested successfully
      utilizing the ammonia field experiments FLADIS T16 and T17.

PMID- 17543448
TI  - Removal and recovery of hazardous triphenylmethane dye, Methyl Violet through
      adsorption over granulated waste materials.
AB  - Bottom Ash a power plant waste material and De-Oiled Soya, an agricultural waste
      product have been successfully used for the removal and recovery of a hazardous
      triphenylmethane dye-Methyl Violet, from wastewaters. The characterization of
      each adsorbent has been carried out by I.R. and D.T.A. curves. Batch adsorption
      studies have been made by measuring effects of pH, sieve size, amount of
      adsorbent, contact time, temperature, concentration of the adsorbate solution,
      etc. Kinetic studies have been used to determine the nature of rate controlling
      step of the processes and confirm the applicability of the first order rate
      expression in the ongoing adsorption process. Various thermodynamic parameters
      have also been calculated by applying the linear forms of Langmuir and Freundlich
      adsorption isotherms. The linear nature of adsorption isotherms obtained shows
      the dependence of the processes on the Freundlich and Langmuir isotherm models.
      Furthermore, to ascertain the adsorption processes to be particle diffusion or
      film diffusion mechanism, Boyd and Reichenberg's expressions have been applied.
      For both the adsorbents, column operations have been carried out for the bulk
      removal of the dye. The adsorbed dye has been recovered by eluting hydrochloric
      acid of pH 3 through exhausted columns.

PMID- 17543449
TI  - Influence of ionic strength in the adsorption and during photocatalysis of
      reactive black 5 azo dye on TiO2 coated on non woven paper with SiO2 as a binder.
AB  - Reactive black 5 (RB5), an azo dye, was degraded by using UV-irradiated TiO(2)
      coated on non woven paper with SiO(2) as a binder. The adsorption capacity of the
      photocatalyst was studied at natural pH, superior to pH(pzc) of the binder, for
      various ionic strengths. Different salts such as NaCl, KCl, CaCl(2), LiCl,
      Ca(NO(3))(2) were used to increase the ionic strength. The presence of salt
      increased the adsorption capacity. The electrostatic interactions between dye and
      oxide surface charges (TiO(2)/SiO(2)) is very important in the adsorption
      phenomena. The effect of the ionic strength of the solution on photocatalyst
      degradation was studied. The rate of degradation was increased by the presence of
      salts in the range of the experimental conditions. The increase of the initial
      decolorization rate was observed in the following order: Ca(2+)>K(+)>Na(+)>Li(+).
      Experiments with different anions (Cl(-), NO(3)(-)) had shown that nitrate was an
      indifferent electrolyte for the adsorption and photodegradation of the dye on
      SiO(2)/TiO(2).

PMID- 17543450
TI  - Bacillus thuringiensis var. israelensis immobilized on Chromosorb 101: a new
      solid phase extractant for preconcentration of heavy metal ions in environmental
      samples.
AB  - Bacillus thuringiensis var. israelensis immobilized on Chromosorb 101 that is a
      new solid phase extractor has been presented at this work for the
      preconcentration and separation of cadmium(II), lead(II), manganese(II),
      chromium(III), nickel(II) and cobalt(II) in environmental samples. The analytical
      parameters including pH of aqueous solutions, sample volume, eluent types, etc.
      were investigated for the quantitative recoveries of the analytes. The influences
      of the some metal ions as concomitant were investigated. Under the optimized
      conditions, the detection limits by 3sigma for analyte ions were in the range of
      0.37-2.85 microg L(-1). The accuracy of the developed procedure was confirmed by
      IAEA 336 Lichen and NIST SRM 1573a Tomato leaves certified reference materials.
      The method was also applied successfully to the determination of analytes in
      microwave digested red wine, rice and canned fish samples and sea water, spring
      water and urine samples.

PMID- 17543451
TI  - Catalysis of advanced oxidation reactions by ultrasound: a case study with
      phenol.
AB  - The present study is about the enhancement in ozone-mediated degradation and UV
      (254nm) photolysis of phenol in aqueous solutions by 300kHz acustic cavitation
      and the selection of operating parameters for optimum phenol removal efficiency.
      The method was based on monitoring of the concentration of phenol during 90min
      exposure to ozonation, sonication, UV photolysis, O(3)/ultrasound, UV/ultrasound
      and O(3)/UV/ultrasound operations. It was found that ozonation at alkaline pH was
      an effective method of phenol destruction, but it was considerably more effective
      when applied simultaneously with ultrasonic irradiation. The observed synergy
      particularly at alkaline pH was attributed to combined effects of: (i) increased
      ozone mass transfer (upon hydrodynamic shear forces created by ultrasonic
      bubbles) and (ii) excess hydroxyl radical formation (upon thermal decomposition
      of ozone in the gaseous cavity bubbles). Degradation of phenol by photolysis
      alone was negligible, while combination of UV-irradiation and ultrasound rendered
      considerable degrees of decay. The synergy here was explained by excess hydroxyl
      radicals that are formed by photolysis of ultrasound-generated H(2)O(2). Maximum
      rate of phenol degradation was observed in case of combined application of ozone,
      UV and ultrasound at basic pH.

PMID- 17543452
TI  - Physical and chemical modification of distillery sludge for Pb(II) biosorption.
AB  - The waste distillery sludge from sugar-cane industry was pretreated physically
      (boiled, heated and autoclaved) as well as chemically (HCl, H(2)SO(4), H(3)PO(4),
      NaOH, Ca(OH)(2), Al(OH)(3), C(6)H(6), HCHO, CH(3)OH and C1(2)H(25)OSO(3)Na
      (sodium dodecyl sulphate (SDS)) for assessing the comparative sorption capacity
      of untreated and modified distillery sludge for Pb(II) biosorption from aqueous
      solutions. Experiments were conducted in shake flasks on a batch basis to access
      the effect of different experimental parameters such as pH, biosorbent dosage,
      biosorbent size, initial Pb(II) concentration and contact time. The uptake
      capacity 'q' (mg/g) of untreated and pretreated distillery sludge was in
      following order: NaOH (51.29+/-1.21)>HCl (49.82+/-1.22)>HCHO (49.56+/
      1.14)>H(2)SO(4) (47.71+/-1.20)>HgCl(2) (45.32+/-1.06)>Ca(OH)(2) (44.01+/
      1.18)>MeOH (43.73+/-1.23)>C(6)H(6) (42.72+/-1.19)>H(3)PO(4) (42.01+/-1.17)>SDS
      (40.87+/-1.27)>autoclaved (40.23+/-1.24)>Boiled (39.95+/-1.19)>heated (38.87+/
      1.32)>Al (OH)(3) (38.30+/-1.14)>untreated (37.76+/-1.21). In further parameter
      studies, the optimized biosorbent size was 0.250 mm at pH 5 and best dose was
      0.05 g of biosorbent. The applicability of the Langmuir and Freundlich models for
      sorption process was tested and best fitted model was Langmuir with the
      coefficient of determination (R(2)) value, 0.97, the process followed second
      order kinetic mechanism.

PMID- 17543453
TI  - Modelling Cr(VI) removal by a combined carbon-activated sludge system.
AB  - The combined carbon-activated sludge process has been proposed as an alternative
      to protect the biomass against toxic substances in wastewaters; however, the
      information about the effect of powdered-activated carbon (PAC) addition in
      activated sludge reactors for the treatment of wastewaters containing Cr(VI) is
      limited. The objectives of the present study were: (a) to evaluate the removal of
      hexavalent chromium by (i) activated sludge microorganisms in aerobic batch
      reactors, (ii) powdered-activated carbon, and (iii) the combined action of
      powdered-activated carbon and biomass; (b) to propose mathematical models that
      interpret the experimental results. Different Cr(VI) removal systems were tested:
      (S1) biomass (activated sludge), (S2) PAC, and (S3) the combined activated carbon
      biomass system. A Monod-based mathematical model was used to describe the
      kinetics of Cr(VI) removal in the system S1. A first-order kinetics with respect
      to Cr(VI) and PAC respectively, was proposed to model the removal of Cr(VI) in
      the system S2. Cr(VI) removal in the combined carbon-biomass system (S3) was
      faster than both Cr(VI) removal using PAC or activated sludge individually.
      Results showed that the removal of Cr(VI) using the activated carbon-biomass
      system (S3) was adequately described by combining the kinetic equations proposed
      for the systems S1 and S2.

PMID- 17543454
TI  - Electrolytic treatment of Standard Malaysian Rubber process wastewater.
AB  - A new method of Standard Malaysian Rubber (SMR) process wastewater treatment was
      developed based on in situ hypochlorous acid generation. The hypochlorous acid
      was generated in an undivided electrolytic cell consisting of two sets of
      graphite as anode and stainless sheets as cathode. The generated hypochlorous
      acid served as an oxidizing agent to destroy the organic matter present in the
      SMR wastewater. For an influent COD concentration of 2960 mg/L at an initial pH
      4.5+/-0.1, current density 74.5 mA/cm(2), sodium chloride content 3% and
      electrolysis period of 75 min, resulted in the following residual values pH 7.5,
      COD 87 mg/L, BOD(5) 60 mg/L, TOC 65 mg/L, total chlorine 146 mg/L, turbidity 7
      NTU and temperature 48 degrees C, respectively. In the case of 2% sodium chloride
      as an electrolyte for the above said operating condition resulted in the
      following values namely: pH 7.2, COD 165 mg/L, BOD(5) 105 mg/L, TOC 120 mg/L,
      total chlorine 120 mg/L, turbidity 27 NTU and temperature 53 degrees C,
      respectively. The energy requirement were found to be 30 and 46 Wh/L, while
      treating 24 L of SMR wastewater at 2 and 3% sodium chloride concentration at a
      current density 74.5 mA/cm(2). The observed energy difference was due to the
      improved conductivity at high sodium chloride content.

PMID- 17543456
TI  - Field efficacy of phoxim 50% (ByeMite) against the poultry red mite Dermanyssus
      gallinae in battery cages stocked with laying hens.
AB  - Infestations with the poultry red mite Dermanyssus gallinae represent a major
      ectoparasite problem in poultry and can affect egg layers worldwide. There is
      presently a lack of an ectoparasiticide in Europe for poultry which can assure a
      0-day withholding period for eggs. In this study, ByeMite (phoxim 50%, Bayer
      HealthCare, Animal Health Division) was administered to treat a D. gallinae
      infestation in a poultry house stocked with egg-laying hens kept in a cage
      system. A layer house was sprayed twice within a 7-day interval using a solution
      containing 2000 ppm phoxim and a similar layer house was used as an untreated
      control unit. Specially developed D. gallinae traps made of cardboard were used
      to assess the mite density in both layer houses during a 49-day period after the
      treatment. In order to collect mites, the traps were placed on days--1, 2, 6, 9,
      13, 20, 34 and 48 and always removed after 24 h. The collected mites were counted
      and differentiated according to their developmental stage (mite eggs, larvae,
      nymphs, adults). Three days after the first spray treatment, the efficacy against
      all mite stages (larvae, nymphs, adults) was 96.1%, and from day 7 post-treatment
      until the end of the trial (day 49) the efficacy exceeded 99%. In contrast, in
      the untreated layer house (negative control group) the mite population showed a
      400% increase. No treatment-related side effects in chickens were detectable. It
      is concluded that two administrations of ByeMite within a 7-day interval are
      highly effective against D. gallinae infestations in a stocked poultry house.

PMID- 17543455
TI  - Isoflurane depression of spinal nociceptive processing and minimum alveolar
      anesthetic concentration are not attenuated in mice expressing isoflurane
      resistant gamma-aminobutyric acid type-A receptors.
AB  - Anesthetics produce immobility and depress spinal nociceptive processing, but the
      exact sites and mechanisms of anesthetic action are unknown. The gamma
      aminobutyric acid type-A (GABAA) receptor is thought to be important to
      anesthetic action. We studied knock-in mice that had mutations in the alpha1
      subunit of the GABAA receptor that imparts resistance to isoflurane in in vitro
      systems. We determined the isoflurane minimum alveolar concentration (MAC) that
      produces immobility in 50% of subjects and responses of lumbar neurons (single
      unit recordings) to noxious stimulation (5 s pinch) of the hindpaw. Isoflurane
      MAC did not differ between wild-type (1.1+/-0.1%) and knock-in (1.1+/-0.1%) mice.
      Isoflurane depressed neuronal responses to noxious stimulation (60 s period
      during and after pinch) similarly in both wild-type and knock-in mice (555+/-133
      and 636+/-106 impulses/min, respectively, at 0.8 MAC and 374+/-81 and 409+/-85
      impulses/min at 1.2 MAC). We conclude that isoflurane enhancement of alpha1
      containing GABAA receptors is not required to produce immobility or depress
      spinal nociceptive processing.

PMID- 17543457
TI  - Pharmacokinetics assessment of moxidectin long-acting formulation in cattle.
AB  - The plasma kinetics disposition of moxidectin following a subcutaneous
      administration with a long-acting formulation (Cydectin) 10%, Fort Dodge Animal
      Health, France) at the recommended dose of 1 mg kg(-1) body weight was evaluated
      in Charolais cattle breed (five females weighing 425-450 kg) for 120 days.
      Furthermore, its concentration was measured in hair for the same period. After
      plasma extraction and derivatization, samples were analysed by HPLC with
      fluorescence detection. Moxidectin was first detected at 1 h after treatment for
      plasma (2.00+/-1.52 ng ml(-1)) and at 2 days for hair (446.44+/-193.26 ng g(-1)).
      The peak plasma concentration (C(max)) was 55.71+/-15.59 ng ml(-1) and 444.44+/
      190.45 ng g(-1) for plasma and hair, respectively. The mean calculated time of
      peak occurrence (T(max)) was 3.40+/-3.36 and 2 days for plasma and hair,
      respectively. The mean residence time (MRT) was 28.93+/-2.87 and 13.32+/-2.48
      days for plasma and hair cattle. The area under concentration-time curve (AUC)
      was 1278.95+/-228.92 ng day ml(-1) and 2663.82+/-1096.62 ng day g(-1) for plasma
      and hair, respectively. At the last sampling time (120 days), the concentration
      was 1.91+/-0.26 ng ml(-1) and 0.69+/-0.52 ng g(-1) for plasma and hair,
      respectively. The bioavailability of this long-acting formulation of moxidectin
      is similar to that registered after subcutaneous administration of moxidectin in
      cattle at 0.2 mg kg(-1) body weight. For the first time the moxidectin
      pharmacokinetics parameters in hair after a subcutaneous administration was
      described. The moxidectin profile concentrations in hair reflected that
      registered in plasma. The previous studies of efficacy have to be correlated to
      the extended period of absorption and distribution by the LA formulation due to
      the fivefold higher dose rate in comparison with the 1% injectable formulation
      (0.2 mg kg(-1) body weight).

PMID- 17543458
TI  - Clinical, haematological, biochemical and economic impacts of Trichinella
      spiralis infection in pigs.
AB  - The purpose of this work was to assess the clinical, haematological and
      biochemical responses of pigs experimentally inoculated with Trichinella
      spiralis. Groups of three pigs were inoculated per os with 100, 500 and 5000 T.
      spiralis muscle larvae, two pigs were used as control. Clinical evaluation of
      disease in pigs included daily examination, rectal temperature measurements and
      cardiac and respiration rates. Haematological studies included: hematocrit (%),
      hemoglobin (g/dl), and white cell, neutrophil, lymphocyte and eosinophil counts.
      Blood biochemistry included: bun (mg/dl), creatinine (mg/dl), AST (UI/l), ALT
      (UI/l), CPK (UI/l) and ALP (UI/l). No significant differences were observed in
      rectal temperature and in cardiac and respiration rates between inoculated
      animals and the control group (p> or =0.05). Significant differences were
      detected (p< or =0.05) in the values of % hemoglobin, and eosinophils, as well as
      in the values of CK, ALP, AST and ALT. The variations observed in some cases were
      related to the number of T. spiralis larvae inoculated and varied with the number
      of days post-infection. Inoculated pigs showed significant differences (p< or
      =0.05) in weight gain when compared with uninoculated controls. This study has
      clinical, haematological, and enzyme alterations in Trichinella infected pigs
      provides a better understanding of acute and chronic trichinellosis in pigs.

PMID- 17543459
TI  - Mouse recombinant leptin protects human hepatoma HepG2 against apoptosis, TNF
      alpha response and oxidative stress induced by the hepatotoxin-ethanol.
AB  - Obesity is a risk factor for hepatocellular carcinoma (HCC) complicated with
      alcoholic liver disease (ALD) and cryptogenic cirrhosis. Leptin is a 16-kDa
      antiobesity hormone secreted mainly by adipocytes. The role of leptin on alcohol
      mediated effects in cell line is yet to be unraveled. Therefore, we investigated
      the effect of leptin against ethanol-elicited cytoxicity in human hepatoma cell
      lines (HepG2). HepG2 cells were treated with leptin (31.2 nM), ethanol (500 mM),
      ethanol+leptin and untreated cells served as control. 48 h after treatment, cell
      viability, apoptosis, TNF-alpha secretory response and oxidative damage were
      analysed. Our results suggest that leptin at a concentration of 31.2 nM prevents
      ethanol elicited cytotoxicity as evidenced by MTT and trypan blue dye exclusion
      assay. Leptin also inhibited ethanol-induced apoptosis, which was confirmed by
      [(3)H] thymidine uptake and cell cycle analysis using propidium iodide (PI)
      staining. Further, simultaneous leptin treatment along with ethanol showed
      protection against ethanol mediated cellular damage as indicated by significantly
      decreased levels of reactive oxygen species (ROS) and thiobarbituric acid
      reactive substances (TBARS) and significantly increased levels of reactive
      nitrogen species (RNS), reduced glutathione (GSH) and elevated activities of
      superoxide dismutase (SOD) and catalase (CAT). In addition, leptin downregulated
      the secretion of tumor necrosis factor-alpha (TNF-alpha) by ethanol-induced HepG2
      cells. Our results demonstrate that simultaneous leptin treatment along with
      ethanol could be useful in preventing the damage produced by ethanol, which might
      be of therapeutic interest.

PMID- 17543460
TI  - Successful management using combination therapy of endotoxin absorption therapy
      (PMX) and continuous hemodiafiltration (CVVHDF) of a critically ill burn patient
      suffering from methicillin-resistant Staphylococcus aureus toxic shock syndrome.

PMID- 17543461
TI  - Nitric oxide, antioxidant capacity, nitric oxide synthase and xanthine oxidase
      plasma levels in a cohort of burn patients.
AB  - BACKGROUND: Nitric oxide (NO) is an important signal molecule in many types of
      cells and tissues. Efficiently balanced NO production was noted to play an
      important role in the healing of burns. However, the exact pathophysiological
      role of NO in burns and its potent relation with clinical and laboratory
      parameters has not been elucidated. METHODS: A cohort of 23 burn patients
      followed for 5 days were enrolled. NO, antioxidant capacity (AC), NO synthase
      (NOS) activity and xanthine oxidase (XO) activity were indirectly determined by
      fluorophotometer. Multiple regression against total burn surface area (TBSA),
      age, weight, height, proximity of septic episode, hemoglobin, white blood cells,
      percent of neutrophils, platelets, glucose, urea, potassium, sodium and albumin
      was performed. RESULTS: Elevation of NO, XO and AC levels is observed from day 2
      (p<0.00001), day 4 (p=0.005) and day 6 (p=0.036), respectively. At the end of
      follow-up period (day 6), NO production was found to independently correlate with
      TBSA, glucose levels and percent of neutrophils (p=0.0004), AC with age,
      hemoglobin and glucose levels (p=0.012), and NOS with proximity of septic episode
      and glucose levels (p=0.027). CONCLUSIONS: NO production exerts its prophylactic
      effect from the first 24h after burn, and is independently correlated with severe
      injury, enhanced neutrophil motivation and augmented glucose levels, thus
      possibly representing a response to stress. This need might trigger induction of
      XO and salvage of antioxidants, as suggested by their rise at a later stage.
      These data underline that an effort to compromise stress and to administer
      antioxidants could be a priority in the treatment of these patients.

PMID- 17543462
TI  - Morphology and physiology of lamina I neurons of the caudal part of the
      trigeminal nucleus.
AB  - It has been suggested that in mammals, trigeminal lamina I neurons play a role in
      the processing and transmission of sensory information from the orofacial region.
      We investigated the physiological and morphological properties of trigeminal
      subnucleus caudalis (Sp5C) lamina I neurons in slices prepared from the medulla
      oblongata of 13- to 15-day-old postnatal rats using patch-clamp recordings and
      subsequent biocytin-streptavidin-Alexa labeling. Twenty-five neurons were
      recorded and immunohistochemically stained. The Sp5C lamina I consisted of
      several types of neurons which, on the basis of their responses to somatic
      current injection, can be classified into four groups: tonic neurons, which fired
      throughout the depolarizing pulse; phasic neurons, which expressed an initial
      burst of action potentials; delayed onset neurons, which showed a significant
      delay of the first action potential; and single spike neurons, characterized by
      only one to five action potentials at the very beginning of the depolarizing
      pulse even at high levels of stimulation intensity. Electrical stimulation of the
      spinal trigeminal tract evoked AMPA receptor-mediated excitatory postsynaptic
      currents (EPSC) exhibiting a strong polysynaptic component. AMPA receptor
      mediated miniature excitatory postsynaptic currents (mEPSC) were characterized by
      a 10-90% rise time of 0.50+/-0.06 ms and a decay time constant of 2.5+/-0.5 ms.
      The kinetic properties of NMDA receptor-mediated EPSCs were measured at +40 mV.
      The 10-90% rise time was 8+/-2 ms and the deactivation time constants were 94+/
      31 and 339+/-72 ms, respectively. Intracellular staining and morphological
      analysis revealed three groups of neurons: fusiform, pyramidal, and multipolar.
      Statistical analysis indicated that the electrophysiological properties and
      morphological characteristics are correlated. Tonic and phasic neurons were
      fusiform or pyramidal and delayed onset and single spike neurons were multipolar.
      Our results show that both the physiological and morphological properties of Sp5C
      lamina I neurons exhibit significant differences, indicating their specific
      integration in the processing and transmission of sensory information from the
      orofacial region.

PMID- 17543463
TI  - Cortical edema in moderate fluid percussion brain injury is attenuated by vagus
      nerve stimulation.
AB  - Development of cerebral edema (intracellular and/or extracellular water
      accumulation) following traumatic brain injury contributes to mortality and
      morbidity that accompanies brain injury. Chronic intermittent vagus nerve
      stimulation (VNS) initiated at either 2 h or 24 h (VNS: 30 s train of 0.5 mA, 20
      Hz, biphasic pulses every 30 min) following traumatic brain injury enhances
      recovery of motor and cognitive function in rats in the weeks following brain
      injury; however, the mechanisms of facilitated recovery are unknown. The present
      study examines the effects of VNS on development of acute cerebral edema
      following unilateral fluid percussion brain injury (FPI) in rats, concomitant
      with assessment of their behavioral recovery. Two hours following FPI, VNS was
      initiated. Behavioral testing, using both beam walk and locomotor placing tasks,
      was conducted at 1 and 2 days following FPI. Edema was measured 48 h post-FPI by
      the customary method of region-specific brain weights before and after complete
      dehydration. Results of this study replicated that VNS initiated at 2 h after
      FPI: 1) effectively facilitated the recovery of vestibulomotor function at 2 days
      after FPI assessed by beam walk performance (P<0.01); and 2) tended to improve
      locomotor placing performance at the same time point (P=0.18). Most
      interestingly, results of this study showed that development of edema within the
      cerebral cortex ipsilateral to FPI was significantly attenuated at 48 h in FPI
      rats receiving VNS compared with non-VNS FPI rats (P<0.04). Finally, a
      correlation analysis between beam walk performance and cerebral edema following
      FPI revealed a significant inverse correlation between behavior performance and
      cerebral edema. Together, these results suggest that VNS facilitation of motor
      recovery following experimental brain injury in rats is associated with VNS
      mediated attenuation of cerebral edema.

PMID- 17543465
TI  - Intrathecal administration of ATP produces long-lasting allodynia in rats:
      differential mechanisms in the phase of the induction and maintenance.
AB  - Several lines of evidence suggest that extracellular ATP plays a role in pain
      signaling through the activation of ionotropic P2X-receptors, especially
      homomeric P2X3- and heteromeric P2X2/3-receptors on capsaicin-sensitive and 
      insensitive primary afferent neurons, respectively, at peripheral and spinal
      sites. We investigated the mechanisms of the induction and maintenance of
      mechanical allodynia produced by a single intrathecal (i.t.) administration of
      ATP in rats. We found that i.t. administration of ATP and the P2X-receptor
      agonist alpha,beta-methylene-ATP produced tactile allodynia which lasted more
      than 1 week. The i.t. ATP- and alpha,beta-methylene-ATP-produced long-lasting
      allodynia remained in neonatal capsaicin-treated adult rats. I.t. administration
      of a P2X3/P2X2/3-receptor selective antagonist completely prevented the induction
      (co-administration on day 0) and partially attenuated the early phase (day 1 post
      ATP administration), but not the late phase (day 7 post-ATP administration) of
      maintenance of allodynia. The N-methyl-D-aspartate (NMDA) receptor antagonist MK
      801 completely prevented the induction phase, but not the early and late phases
      of maintenance of allodynia. Immunohistochemical and immunoblotting studies for
      microglial and astrocytic markers revealed that i.t. ATP administration caused
      spinal microglial activation within 1 day, and astrocytic activation which peaked
      at 1-3 days after ATP administration. Furthermore, minocycline, a microglial
      inhibitor, attenuated the induction but not the early and late phases of
      maintenance, while fluorocitrate, a glial metabolic inhibitor, attenuated the
      induction and the early phase but not the late phase of maintenance. Taken
      together, these results suggest that the activation of P2X-receptors, most likely
      spinal P2X2/3-receptors on capsaicin-insensitive primary afferent neurons,
      triggers the induction of long-lasting allodynia through NMDA receptors, and the
      induction and early maintenance phase, but not the late phase, is mediated
      through the functions of spinal glial cells.

PMID- 17543464
TI  - Prenatal cocaine exposure enhances responsivity of locus coeruleus norepinephrine
      neurons: role of autoreceptors.
AB  - Children exposed to cocaine during gestation have a higher incidence of
      neurobehavioral deficits. The neurochemical bases of these deficits have not been
      determined, but the pharmacology of cocaine and the nature of the abnormalities
      suggest that disruptions in catecholaminergic systems may be involved. In the
      current study, we used a rat model of prenatal cocaine exposure to examine the
      impact that this exposure has on the locus coeruleus (LC) noradrenergic system in
      offspring. Pregnant rats received twice-daily i.v. injections of cocaine (3
      mg/kg) or saline between gestational days 10 and 20, and progeny were tested as
      juveniles. Exposure to a mild stressor elevated an index of norepinephrine
      turnover in the prefrontal cortex and also increased Fos expression in tyrosine
      hydroxylase-positive LC neurons in rats exposed to prenatal cocaine but not in
      rats exposed to prenatal saline. No change in the number of tyrosine hydroxylase
      positive neurons in the LC was observed between the two prenatal treatment
      groups. Specific binding of [125I]-para-iodoclonidine, a radioligand with
      specificity for high affinity alpha2A-adrenergic receptors, was decreased in the
      LC of rats exposed to prenatal cocaine compared with prenatal saline controls. As
      alpha2-adrenergic receptors on LC norepinephrine neurons function as
      autoreceptors, their down-regulation by prenatal cocaine exposure provides a
      plausible mechanism for the observed heightened reactivity of norepinephrine
      neurons in these animals. These data indicate that prenatal cocaine exposure
      results in lasting changes to the regulation and responsivity of rat LC
      norepinephrine neurons. A similar dysregulation of LC norepinephrine neurons may
      occur in children exposed to cocaine during gestation, and this may explain, at
      least partly, the increased incidence of cognitive deficits that have been
      observed in these subjects.

PMID- 17543466
TI  - Preventive effects of intrathecal methylprednisolone administration on spinal
      cord ischemia in rats: the role of excitatory amino acid metabolizing systems.
AB  - Spinal cord ischemic injury usually results in paraplegia, which is a major cause
      of morbidity after thoracic aorta operations. Ample evidence indicates that
      massive release of excitatory amino acids (EAAs; glutamate) plays an important
      role in the development of neuronal ischemic injuries. However, there is a lack
      of direct evidence to indicate the involvement of EAAs in the glutamate
      metabolizing system (including the glutamate transporter isoforms, i.e. the Glu
      Asp transporter (GLAST), Glu transporter-1 (GLT-1), and excitatory amino acid
      carrier one (EAAC1); glutamine synthetase (GS); and glutamate dehydrogenase
      (GDH)) in spinal cord ischemia. In the present results, we found that
      methylprednisolone (MP; intrathecal (i.t.) injection, 200 mug twice daily
      administered for 3 days before ischemia), a synthetic glucocorticoid, is the
      therapeutic agent for the treatment of spinal injuries in humans, can
      significantly reduce the ischemia-induced motor function defect and down-regulate
      the glutamate metabolizing system (including GLAST, GLT-1, GS, and GDH) in male
      Wistar rats. The spinal cord ischemia-induced down-regulation of EAAC1 protein
      expression in the ventral portion of the lumbar spinal cord was partly inhibited
      by pretreatment with i.t. MP. However, MP did not affect the down-regulation of
      EAAC1 in the dorsal portion of the lumbar spinal cord after spinal cord ischemia.
      The i.t. injection of MP alone did not change the neurological functions and the
      expression of proteins of the glutamate metabolizing system in the spinal cord.
      Our results indicate that spinal cord ischemia-induced neurological deficits
      accompany the decrease in the expression of proteins of the glutamate
      metabolizing system in the lumbar portion of the spinal cord. The i.t. MP
      pretreatment significantly prevented these symptoms. These results support the
      observation that MP delivery through an i.t. injection, is beneficial for the
      treatment of spinal cord ischemic injuries.

PMID- 17543467
TI  - Embryonic and postnatal development of the serotonergic raphe system and its
      target regions in 5-HT1A receptor deletion or overexpressing mouse mutants.
AB  - The neurotransmitter 5-HT regulates early developmental processes in the CNS. In
      the present study we followed the embryonic and postnatal development of
      serotonergic raphe neurons and catecholaminergic target systems in the brain of 5
      HT1A receptor knockout (KO) and overexpressing (OE) in comparison with wild-type
      (WT) mice from embryonic day (E) 12.5 to postnatal day (P) 15.5. Up to P15.5 no
      differences were apparent in the differentiation and distribution of serotonergic
      neurons in the raphe area as revealed by the equal number of serotonergic neurons
      in the dorsal raphe in all three genotypes. However, the establishment of
      serotonergic projections to the mesencephalic tegmentum and hypothalamus was
      delayed at E12.5 in KO and OE animals and projections to the cerebral cortex
      between E16.5 and E18.5 were delayed in OE mice. This delay was only transient
      and did not occur in other brain areas including septum, hippocampus and
      striatum. Moreover, OE mice caught up with WT and KO animals postnatally such
      that at P1.5 serotonergic innervation of the cortex was more extensive in the OE
      than in KO and WT mice. Tissue levels of 5-HT and of its main metabolite 5
      hydroxyindoleacetic acid as well as 5-HT turnover were considerably higher in
      brains of OE mice and slightly elevated in KO mice in comparison with the WT,
      starting at E16.5 through P15.5. The initial differentiation of dopaminergic
      neurons and fibers in the substantia nigra at E12.5 was transiently delayed in KO
      and OE mice as compared with WT mice, but no abnormalities in noradrenergic
      development were apparent in later stages. The present data indicate that 5-HT1A
      receptor deficiency or overexpression is associated with increased 5-HT synthesis
      and turnover in the early postnatal period. However, they also show that effects
      of 5-HT1A KO or OE on the structural development of the serotonergic system are
      at best subtle and transient. They may nonetheless contribute to the
      establishment of increased or reduced anxiety-like behavior, respectively, in
      adult mice.

PMID- 17543468
TI  - Immunohistochemical expression and colocalization of somatostatin,
      carboxypeptidase-E and prohormone convertases 1 and 2 in rat brain.
AB  - The processing of many peptides for their maturation in target tissue depends
      upon the presence of sorting receptor. Several previous studies have predicted
      that carboxypeptidase-E (CPE), prohormone convertase 1 (PC1) and prohormone
      convertase 2 (PC2) may function as sorting elements for somatostatin (SST) for
      its maturation and processing to appropriate targets. However, nothing is
      currently known about whether brain, neuronal culture or even endocrine cells
      express SST, CPE, PC1 and PC2 and exhibit colocalization. Accordingly, in the
      present study using peroxidase immunohistochemistry, double-labeled indirect
      immunofluorescence immunohistochemistry and Western blot analysis, we mapped the
      distributional pattern of SST, CPE, PC1 and PC2 in different rat brain regions.
      Additionally, we also determined the colocalization of SST with CPE, PC1 and PC2
      as well as colocalization of CPE with PC1 and PC2. The localization of SST, CPE,
      PC1 and PC2 reveals a distinct and region specific distribution pattern in the
      rat brain. Using an indirect double-label immunofluorescence method we observed
      selective neuron specific colocalization in a region specific manner in cortex,
      striatum and hippocampus. These studies provide the first evidence for
      colocalization between SST, CPE, PC1 and PC2 as well as CPE with PC1 and PC2. SST
      in cerebral cortex colocalized in pyramidal and non-pyramidal neurons with CPE,
      PC1 and PC2. Most importantly, in striatum and hippocampus colocalization was
      mostly observed selectively and preferentially in interneurons. CPE is also
      colocalized with PC1 and PC2 in a region specific manner. The data presented here
      provide a new insight into the distribution and colocalization of SST, CPE, PC1
      and PC2 in rat brain. Taken together, our data anticipate the possibility that
      CPE, PC1 and PC2 might be potential target for the maturation of SST.

PMID- 17543469
TI  - Analysis of 5-HT6 and 5-HT7 receptor gene expression in rats showing differences
      in novelty-seeking behavior.
AB  - Sensation-seeking is a human personality trait associated with a greater
      propensity to use psychoactive substances. A rat model showing face validity of
      this human trait has been developed. The model is based on the variety of
      behavioral responses that rats exhibit in a novel and inescapable environment,
      with some animals (high-responders, HR) being highly active, and others (low
      responders, LR) showing less exploration. More active rats (HR) also show
      increased drug-taking and decreased anxiety-like behavior. There is evidence that
      response to novelty may rely on differential 5-HT-mediated neurotransmission.
      This research focuses on the recently discovered 5-HT6 and 5-HT7 receptors which
      share affinity for neuroleptic drugs and hallucinogens. To date, emerging
      evidence suggests that 5-HT6 and 5-HT7 may be involved in cognition and mood
      regulation, respectively. To further our knowledge of their behavioral
      attributes, we compared patterns of gene expression for these receptors in the
      brains of HR and LR rats. As a control, gene expression for the 5-HT3 receptor
      was investigated because its contribution to anxiety and addiction is only weakly
      demonstrated. Transcript levels for 5-HT6 in the olfactory tubercle inversely
      correlated with the level of locomotion in a novel environment. Phenotype
      differences in mRNA signal for 5-HT6 showed a complex pattern in the dentate
      gyrus. LR rats were statistically higher in the most anterior region of the
      dentate gyrus, while HR rats were higher in median areas of the dentate gyrus.
      Levels of 5-HT7 transcript in HR rats were significantly lower than LR rats in
      pivotal areas for information trafficking, such as thalamo-cortical projection
      areas and dorsal hippocampus. By contrast, phenotype differences in 5-HT3
      expression were not found in areas of the limbic cortex and mesolimbic system.
      Taken together, these results provide new insight into the potential contribution
      of 5-HT to novelty-seeking behavior and associated behaviors such as substance
      abuse.

PMID- 17543470
TI  - Raloxifene acutely reduces glutamate-induced intracellular calcium increase in
      cultured rat cortical neurons via inhibition of high-voltage-activated calcium
      current.
AB  - There is increasing evidence indicating that estrogen replacement therapy
      produces neuroprotective actions but has undesirable side effects on the
      reproductive system. Raloxifene is a selective estrogen receptor modulator that
      exerts estrogen agonist action in the brain while acting as an estrogen
      antagonist in the reproductive system. In the present study, we investigated
      whether raloxifene affected the glutamate-induced calcium (Ca2+) overload in rat
      cultured cortical neurons. The bulk cytosolic intracellular Ca2+ level was
      measured by using confocal microscopy with fluorescent Ca2+ probe fluo3. Whole
      cell recording technique was used to observe the effects of raloxifene on N
      methyl-D-aspartate (NMDA)-evoked and voltage-activated Ca2+ currents in cultured
      cortical neurons. Pre-exposure of cortical neurons to raloxifene (0.5 microM-10
      microM) for 3 min attenuated intracellular Ca2+ increase induced by application
      of glutamate (300 microM) for 1 min. The action of raloxifene was reversible
      after washout. ICI 182,780 and thapsigargin did not block the action of
      raloxifene. In whole-cell recording experiments, raloxifene (10 microM)
      significantly reduced the amplitude of the high-voltage-activated Ca2+ current
      but had no effect on NMDA-evoked Ca2+ current. The present study demonstrates
      that raloxifene acutely reduces glutamate-induced intracellular Ca2+ increase
      probably via inhibition of high-voltage-activated calcium channels.

PMID- 17543471
TI  - Neurocognitive effects of alcohol hangover.
AB  - Alcohol hangover is characterized by adverse physical and mental effects that
      occur the next morning after the intake of toxic doses of alcohol. One of the
      more relevant functional consequences of hangover is the cognitive and subjective
      impairment, which could be related to the high socioeconomic costs of alcohol
      consumption. Nevertheless, few studies have addressed the study of neurocognitive
      and subjective effects of hangover. The systematic and exhaustive study of
      neurocognitive and subjective effects has not been done. In the present work we
      briefly review the hangover impact, not only in the objective execution of
      attention, psychomotricity and memory tasks, but in the subjective state of the
      subjects as well. Moreover, we also highlight the methodology difficulties to
      study neurocognitive effects of hangover and suggest several aspects to take into
      account in future investigations.

PMID- 17543472
TI  - Illusory predictors: Generalizability of findings in cocaine treatment retention
      research.
AB  - Treatment retention is of paramount importance in cocaine treatment research as
      treatment completion rates are often 50% or less. Failure to retain cocaine
      patients in treatment has both significant research and clinical implications. In
      this paper we qualitatively and quantitatively demonstrate the inconsistency
      found across analyses of retention predictors in order to highlight the problem.
      First, a qualitative review of the published literature was undertaken to
      identify the frequency of predictors studied and their relations to treatment
      retention. Second, an empirical demonstration of predictor stability was
      conducted by testing a common set of variables across three similar 12-week
      cocaine clinical trials conducted by the same investigators in the same research
      clinic within a five-year period. Results of the literature review indicated
      inconsistently selected variables of convenience, widely varying statistical
      procedures, and discrepant findings of significance. Further, quantitative
      analyses resulted in discrepancies in variables identified as significant
      predictors of retention among the three studies. Potential sources of
      heterogeneity affecting the consistency of findings across studies and
      recommendations to improve the validity and generalizability of predictor
      findings in future studies are proposed.

PMID- 17543473
TI  - Scientific discovery, peak experiences and the Col-oh-nell Flastratus!
      phenomenon.
AB  - Once I had a bizarre dream in which I was vouchsafed a secret which would ensure
      my wealth and success. It was the title for a comic novel; one supposedly so
      funny that it would guarantee classic status for any book: Oh Colonel Flastratus!
      The distinctive feature about my dream was its quality of profound significance,
      which felt akin to the Eureka moment of a scientific discovery. This led me to
      question whether the 'peak experience' (PE) of scientific discovery might be as
      delusional as my dream. On the one hand, euphoric elation attached to a discovery
      does not guarantee that insights objective truth - implications must be spelled
      out and checked. The easy induction of pseudo-profound insights by intoxicants
      serves as a warning of the potential pitfalls. An arbitrary object becomes
      labeled with an obscure sense of delight and personal relevance in a process that
      could be termed the Colonel Flastratus! phenomenon. But neither are peak
      experiences irrelevant. A scientific PE is some kind of personal guarantee of the
      subjective truth of an insight - a signal that states: 'This is high quality
      stuff, by your standards. Do not ignore it, do not forget it, try to understand
      it'. Peak experiences in science could therefore be considered the result of a
      'significance alarm' going off in the brain and their objective value depends on
      the specialized cognitive quality of that specific brain. So scientists may be
      correct to take peak experiences seriously. Perhaps the best approach is to
      regard the scientific PE as a signal from the self to the self, a subjectively
      evaluated and auto-administered emotional reward for good thinking.

PMID- 17543474
TI  - Efficiency of immunohistochemical p16 expression and HPV typing in cervical
      squamous intraepithelial lesion grading and review of the p16 literature.
AB  - Diagnosing and grading cervical cancer precursors is challenging. This study
      investigates the presence of HPV infection, the expression of p16, and any
      correlation between these two findings. H&E-stained slides of cervical loop
      excision materials diagnosed as LSIL and HSIL were reviewed. An
      immunohistochemical panel consisting of p16 as well as of all HPV types and HR
      HPV types was applied. Staining of p16 was evaluated according to distribution
      extent and degree of intensity. All HSIL cases and 80% of LSIL cases were
      positive for p16. In HSIL cases, the staining distribution was as follows: 50%
      full thickness, 45% basal, and 5% rare. The staining intensity for the same cases
      was strong in 70%, variable in 20%, and weak in 10% accordingly. In LSIL cases,
      staining distribution was basal in 58.3% and rare in 41.7%. None of the LSIL
      cases showed full thickness of p16 positivity. The staining intensity of the same
      cases was strong in 25%, variable in 16.7%, and weak in 58.3%. Of all cases,
      48.6% were positive for screening kit (all HPV types), and 31.4% of all cases
      were positive for HR-HPV. The distribution of this positivity was 35% for HSIL
      and 26.6% for LSIL cases. The total HPV-type positivity rate was 48.6%, the
      distribution being 50% for HSIL and 46.6% for LSIL cases. p16 is a highly
      sensitive marker for cervical epithelial dysplasia. Strong and full thickness
      staining of p16 in the cervix epithelium is highly supportive of HSIL, while weak
      and basal/rare staining favors LSIL. All HPV-positive cases were also p16
      positive, but no statistically significant relationship between HPV infection
      positivity and the intensity and distribution of p16 was found. HPV is not
      helpful in the grading of SIL, as an unignorable rate of HR-HPV positivity
      (26.6%) was detected in LSIL group.

PMID- 17543475
TI  - [Role of the professional use of Internet for the trainees of the gynecology
      obstetrics program in Lille in 2005].
AB  - OBJECTIVE: To describe the professional impact of Internet for trainees and to
      assess the need for Internet classes. MATERIAL AND METHODS: A questionnaire was
      distributed to all trainees of the gynaecology-obstetrics program in Lille. We
      evaluated the use of Internet and its consequence on the professional life. The
      search engine Pubmed was especially studied as a representation of the
      professional use of the Internet. Trainees were classified in "young" (first 2
      years) and "old" (last 3 years). RESULTS: The ability to obtain medical
      information online was strong as 98% of the participants reported using the
      Internet. However, more traditional tools such as manuals were used to find a
      medical information despite an early use of the Internet (mainly started in
      medical school). We did not find any differences between the two trainee groups
      in the use of Pubmed. Sixty-four percent of the young trainees were using Pubmed
      compared to 100% of their seniors (P<0,05). Old trainees were more frequently
      medium-levelled (50 versus 14%; P<0,05) whereas 57% young trainees were low
      levelled. Old trainees were more familiar with the use of links to online
      publications (43 versus 11%; P<0,05). Eighty-five percent of the trainees
      experienced difficulties using the Internet or Pubmed. CONCLUSION: Access to the
      Internet increases rapidly among physicians and medical students. However, they
      may encounter difficulties using search engine online. Our data support the
      hypothesis that residents should learn how to use the Internet effectively for
      searching medical resources. We suggest to planning classes during the residency
      program.

PMID- 17543476
TI  - Adolescent smokers rate delayed rewards as less certain than adolescent
      nonsmokers.
AB  - This research compared adolescent smokers (n=45) and nonsmokers (n=35) on ratings
      of certainty about receiving delayed rewards during a delay discounting
      procedure. Consistent with a previous finding [Patak, M., Reynolds, B., 2007.
      Question-based assessments of delay discounting: do respondents spontaneously
      incorporate uncertainty into their valuations for delayed rewards? Addict. Behav.
      32, 351-357] participants generally rated the delayed rewards as increasingly
      uncertain with longer delays, and ratings of certainty were correlated with delay
      discounting (r=.37). Also, the adolescent smokers rated the delayed rewards as
      significantly less certain than the nonsmokers. These findings indicate that
      adolescents who smoke cigarettes evaluate delayed outcomes as less certain than
      adolescents who do not smoke cigarettes.

PMID- 17543477
TI  - The psychrophilic bacterium Pseudoalteromonas halosplanktis TAC125 possesses a
      gene coding for a cold-adapted feruloyl esterase activity that shares homology
      with esterase enzymes from gamma-proteobacteria and yeast.
AB  - The complete genome of the psychrophilic bacteria Pseudoalteromonas haloplanktis
      TAC 125, recently published, owns a gene coding for a putative esterase activity
      corresponding to the ORF PSHAa1385, also classified in the Carbohydrate Active
      Enzymes database (CAZY) belonging to family 1 of carbohydrate esterase proteins.
      This ORF is 843 bp in length and codes for a protein of 280 amino acid residues.
      In this study we characterized and cloned the PSHAa1385 gene in Escherichia coli.
      We also characterized the recombinant protein by biochemical and biophysical
      methodologies. The PSHAa1385 gene sequence showed a significant homology with
      several carboxyl-esterase and acetyl-esterase genes from gamma-proteobacteria
      genera and yeast. The recombinant protein exhibited a significant activity
      towards pNP-acetate, alpha-and beta-naphthyl acetate as generic substrates, and 4
      methylumbelliferyl p-trimethylammonio cinnamate chloride (MUTMAC) as a specific
      substrate, indicating that the protein exhibits a feruloyl esterase activity that
      it is displayed by similar enzymes present in other organisms. Finally, a three
      dimensional model of the protein was built and the amino acid residues involved
      in the catalytic function of the protein were identified.

PMID- 17543478
TI  - Malignant catarrhal fever-like lesions associated with ovine herpesvirus-2
      infection in three goats.
AB  - This is the first description of malignant catarrhal fever-like lesions
      associated with ovine herpesvirus-2 (OvHV-2) infection in goats with central
      nervous symptoms. The diagnosis was based on typical histological lesions
      characterized by systemic lymphohistiocytic and fibrinoid vasculitis and
      confirmed by polymerase chain reaction and subsequent phylogenetic analysis of
      the detected OvHV-2 sequences.

PMID- 17543479
TI  - Nationwide molecular surveillance of exfoliative toxigenic Staphylococcus hyicus
      on pig farms across Japan.
AB  - We investigated the carriage of Staphylococcus hyicus and their exfoliative toxin
      genes (exhA, exhB, exhC, exhD, and shetb) among 424 pigs from 38 Japanese pig
      farms by PCR and characterized the isolates by 16S-23S intergenic spacer region
      polymorphism analysis. S. hyicus (n=207) were isolated from 17.9% of pigs and
      72.5% of them were toxigenic. The isolation rate of toxigenic S. hyicus was four
      times higher in the pigs with exudative epidermitis than the healthy pigs (87.6%
      versus 19.6%; p<0.01). Among the toxins, exhA was the most prevalent, being
      detectable in 49.3% of toxin gene-positive strains. S. hyicus isolates were
      distributed into nine ITS-PCR types (a-i), with ITS-PCR types d, h, and e being
      predominant accounting for 70% (145/207) of total isolates or 76% (114/150) of
      toxin gene-positive strains. This study denotes high prevalence of toxigenic
      strains among S. hyicus circulating on pig farms in Japan.

PMID- 17543480
TI  - Differentiation of feline coronavirus type I and II infections by virus
      neutralization test.
AB  - Feline coronavirus (FCoV) is divided into two types I and II, based on their
      growth in vitro and antigenicity. In this study, virus neutralization (VN) test
      was applied for type differentiation of FCoV infections. Sera of cats which were
      clinically and serologically diagnosed as feline infectious peritonitis (FIP)
      possessed significantly higher VN titers to type I FCoV, and sera from cats
      experimentally infected with FIPV type II had high VN titers to type II but not
      type I viruses. A total of 79 cat sera collected in the years between 2004 and
      2005 were examined to evaluate seroprevalence by the VN test, showing the
      following results: (1) 50 cats (63.3%) were sero-positive to FCoV; (2) of the 50
      FCoV positive cat serum samples, 49 (98%) showed significantly higher titers to
      type I virus and only one (2%) for type II virus. These results indicate that the
      VN test described here can be used for serological differentiation of FCoV
      infections of cats, and that FCoV type I is a dominant type in recent years of
      Japan.

PMID- 17543481
TI  - Acetaldehyde induces matrix metalloproteinase-9 gene expression via nuclear
      factor-kappaB and activator protein 1 signaling pathways in human hepatocellular
      carcinoma cells: Association with the invasive potential.
AB  - Alcohol consumption is a significant risk factor for hepatocellular carcinoma
      (HCC). Alcohol also increases the prevalence of invasion in HCC patients.
      However, the molecular mechanism on the metastatic effect of alcohol is unclear
      so far. Herein we demonstrated that acetaldehyde, the primary metabolite of
      ethanol, increased matrix metalloproteinase-9 (MMP-9) gelatinolytic activity and
      promoted cell invasion through the up-regulation of MMP-9 gene transcription in
      HepG2 cells. The transcription of MMP-9 gene was regulated by 10 microM
      acetaldehyde via inductions of nuclear factor-kappaB (NF-kappaB) and activator
      protein 1 (AP-1) activities. Acetaldehyde stimulated the translocation of NF
      kappaB into nucleus through inhibitory kappaB-alpha (IkappaB-alpha) and c-Jun N
      terminal kinase (JNK)/beta-transducin repeat-containing protein (beta-TrCP)
      signaling pathways. Acetaldehyde also induced AP-1 activity via the
      phosphorylation of p38 kinase. In conclusion, our findings demonstrated for the
      first time that acetaldehyde activated NF-kappaB and AP-1 activities via IkappaB,
      JNK/beta-TrCP, and p38 signaling pathways, resulting in MMP-9 gene expression and
      hepatocarcinoma cells invasion. These results suggested that acetaldehyde might
      be a potential factor involved in the invasiveness of HCC in alcoholic patients.

PMID- 17543482
TI  - Induction of estrus in pubertal miniature gilts.
AB  - Genetic engineering of miniature pigs has facilitated the development of numerous
      biomedical applications, such as xenotransplantation and animal models for human
      diseases. Manipulation of the estrus is one of the essential techniques for the
      generation of transgenic offspring. The purpose of the present study was to
      establish a useful method for induction of the estrus in miniature gilts. A total
      of 38 pubertal miniature gilts derived from 4 different strains were treated with
      exogenous gonadotropins. Estrus and ovulatory response were examined after
      treatment with pregnant mare serum gonadotropin (PMSG) and human chorionic
      gonadotropin (hCG) as 200 IU PMSG and 100 IU hCG, 300 IU PMSG and 150 IU hCG, or
      1,500 IU PMSG only, followed by 100, 150 or 750 IU hCG 72 h later, respectively.
      The optimal protocol was determined to be the combination treatment of 200 IU
      PMSG and 100 IU hCG followed by 100 IU hCG. The administration of 200 IU PMSG and
      100 IU hCG was effective in inducing estrus regardless of the strain, although
      there was a strain difference in the ovulatory response. These results indicate
      that treatment with a low-dose combination of PMSG and hCG provides one of the
      simplest methods for induction of estrus and ovulation in pubertal miniature
      pigs.

PMID- 17543483
TI  - In vitro effects of a fraction separated from Polygonum cuspidatum root on the
      viability, in suspension and biofilms, and biofilm formation of mutans
      streptococci.
AB  - Polygonum cuspidatum (Polygonaceae) has traditionally been used in folk medicine
      to control oral diseases. Nevertheless, there are no reports related to its
      possible effect on the diseases, particularly on biofilm-related diseases such as
      dental caries. In this study, we evaluated in vitro effects of a fraction
      separated from Polygonum cuspidatum root on the viability, in both suspension and
      biofilms, and the biofilm formation of mutans streptococci. The separated
      fraction (F1) showed bacteriostatic and bactericidal activity against mutans
      streptococci in suspension, with minimum inhibitory concentration (MIC) range of
      31.3-250 microg/ml and minimum bactericidal concentration (MBC) range of 0.5-1
      mg/ml. At a concentration of 1.5 mg/ml, F1 killed approximately 2 log(10)CFU/ml
      of Streptococcus mutans and Streptococcus sobrinus after 2h of exposure. In
      biofilms, F1 also inhibited the viability of Streptococcus mutans and
      Streptococcus sobrinus, dependent on the biofilm age, the concentration of F1,
      and the treatment time. Four hours of exposure to 1.5 mg/ml F1 reduced the viable
      counts of Streptococcus mutans and Streptococcus sobrinus by greater than 2
      log(10)CFU/disc. Furthermore, at sub-MIC levels, F1 inhibited biofilm formation
      by Streptococcus mutans and Streptococcus sobrinus in a dose-dependent fashion.
      Based on the preliminary phytochemical analysis, the activity of F1 may be
      related to the presence of anthraquinones, cardiac glycosides, terpenoids, and
      phenolics. These results indicate that F1 is probably useful in the control of
      oral biofilms and subsequent dental caries development.

PMID- 17543484
TI  - Evaluation of haplotype discrimination capacity of 35 Y-chromosomal short tandem
      repeat loci.
AB  - The haplotype discrimination capacity of the 9 Y-chromosomal short tandem repeat
      (Y-STR) loci comprising the so called minimal haplotype together with additional
      26 recently described single-copy Y-STRs was evaluated within 391 males from
      Germany, The Netherlands, and Turkey. The aim of this study was to identify the
      minimum number of Y-STRs needed in addition to the recommended 9 minimal
      haplotype loci or the 11 SWGDAM loci for individualizing male lineages. Highest
      gene diversities were shown for DYS385 loci, DYS449, DYS481, DYS570, DYS447,
      DYS576, DYS389-II, and DYS390 (D=0.7518-0.8746). The five Y-STRs DYS447, DYS449,
      DYS481, DYS570, and DYS576 comprised the smallest set of loci in addition to the
      previously recommended standard Y-STRs leading to the individualization of all
      males from each single population group. Complete resolution of the pooled
      population was achieved by the additional genotyping of two further loci, DYS446
      or DYS505 and DYF406S1 or DYS522.

PMID- 17543486
TI  - Imaging of the hip in patients with rheumatic disorders.
AB  - Hip joint abnormalities are commonly encountered in patients with rheumatic
      disorders. Although conventional radiography remains the mainstay for diagnosis
      of joint damage and subsequent follow-up, magnetic resonance imaging and, to a
      lesser extent, ultrasound have afforded the ability to detect early signs of
      articular involvement (i.e., synovitis and bone erosions), and to assess disease
      activity in treated patients. In more advanced stages of rheumatic disorders,
      magnetic resonance imaging and ultrasound are both useful in assessing
      paraarticular involvement (i.e., bursitis and synovial cysts).

PMID- 17543485
TI  - Genes that may modulate longevity in C. elegans in both dauer larvae and long
      lived daf-2 adults.
AB  - We used Serial Analysis of Gene Expression (SAGE) to compare the global
      transcription profiles of long-lived mutant daf-2 adults and dauer larvae, aiming
      to identify aging-related genes based on similarity of expression patterns. Genes
      that are expressed similarly in both long-lived types potentially define a common
      life-extending program. Comparison of eight SAGE libraries yielded a set of 120
      genes, the expression of which was significantly different in long-lived worms
      vs. normal adults. The gene annotations indicate a strong link between oxidative
      stress and life span, further supporting the hypothesis that metabolic activity
      is a major determinant in longevity. The SAGE data show changes in mRNA levels
      for electron transport chain components, elevated expression of glyoxylate shunt
      enzymes and significantly reduced expression for components of the TCA cycle in
      longer-lived nematodes. We propose a model for enhanced longevity through a
      cytochrome c oxidase-mediated reduction in reactive oxygen species commonly held
      to be a major contributor to aging.

PMID- 17543487
TI  - Imaging patellar complications after knee arthroplasty.
AB  - The purpose of this study is to describe complications affecting the patella in
      patients with total or partial knee arthroplasty. We respectively analysed plain
      film radiographs, as well as ultrasound images when acquired, in a consecutive
      series of 1272 patients. The mean interval from knee replacement to patellar
      complications was 5 years and 7 months (range, 5 months to 14 years). The
      complications described include fracture, instability, dislocation or luxation,
      necrosis of the patella, infection of the patella, erosion of the patella,
      patellar impingement on the prosthesis and patellar or quadricipital tendon tear.
      We discuss the pathological imaging findings in the patella and their
      differential diagnosis after knee arthroplasty. Patellar complications after knee
      arthroplasty are uncommon but often potentially serious.

PMID- 17543488
TI  - Long-term postplacement cost after endovascular aneurysm repair.
AB  - BACKGROUND: Previous studies have demonstrated that the initial hospital cost
      associated with endovascular aneurysm repair (EVAR) is approximately $20,000.
      However, the cost of long-term surveillance and secondary procedures is poorly
      characterized. METHODS: Between December 1998 and June 2006, 259 patients
      underwent EVAR for infrarenal aneurysms at a single institution. Follow-up costs
      were calculated using a relative value unit based hospital cost accounting
      system, which incorporates departmental direct and indirect costs. Institutional
      overhead costs were included using a conversion factor. Costs for professional
      services were determined by a cost-to-charge ratio, and outpatient visits were
      calculated with a time-based formula. Year 2006 costs were applied to prior
      years. To minimize costs associated with the early learning curve, the initial 50
      EVAR patients between December 1995 and 1998 were excluded. Patients with <1 year
      follow-up were also excluded. Data are expressed as mean +/- standard error.
      RESULTS: The mean follow-up after EVAR for 136 patients was 34.7 +/- 1.8 months.
      The cumulative 5-year postplacement cost per patient was $11,351. The 27 patients
      (19.9%) who required secondary procedures had a 5-year cumulative cost of $31,696
      compared with $3668 for 109 patients without secondary procedures (8.6-fold
      increase, P < .05). The 5-year cost for patients with endoleak was $26,739
      compared with $5706 for those without endoleak (4.7-fold increase, P < .05).
      Overall, major cost components were 57.4% for secondary procedures and 32.5% for
      radiologic studies. CONCLUSIONS: During a 5-year period, the postplacement cost
      of EVAR increases the global cost by 44%. The subgroups of patients with
      endoleaks and those requiring secondary procedures generate a disproportionate
      share of postplacement costs. Efforts at minimizing cost should emphasize
      technical and device modifications aimed at reducing endoleaks and the need for
      secondary procedures.

PMID- 17543489
TI  - Persistent type 2 endoleak after endovascular repair of abdominal aortic aneurysm
      is associated with adverse late outcomes.
AB  - OBJECTIVE: Type 2 endoleak occurs in up to 20% of patients after endovascular
      aneurysm repair (EVAR), but its long-term significance is debated. We reviewed
      our experience to evaluate late outcomes associated with type 2 endoleak.
      METHODS: During the interval January 1994 to December 2005, 873 patients
      underwent EVAR. Computed tomography (CT) scan assessment was performed < or =1
      month of the operation and at least annually thereafter. Sequential 6-month CT
      scan follow-up was adopted for those patients with persistent type 2 endoleaks,
      and reintervention was limited to those with sac enlargement >5 mm. Study end
      points included overall survival, aneurysm sac growth, reintervention rate,
      conversion to open repair, and abdominal aortic aneurysm (AAA) rupture.
      Preoperative variables and anatomic factors potentially associated with these
      endpoints were assessed using multivariate analysis. RESULTS: We identified 164
      (18.9%) patients with early (at the first follow-up CT scan) type 2 endoleaks.
      Mean follow-up was 32.6 months. In 131 (79.9%) early type 2 endoleaks, complete
      and permanent leak resolution occurred < or =6 months. Endoleaks persisted in 33
      patients (3.8% of total patients; 20.1% of early type 2 endoleaks) for >6 months.
      Transient type 2 endoleak (those that resolved < or =6 months of EVAR) was not
      associated with adverse late outcomes. In contrast, persistent endoleak was
      associated with several adverse outcomes. AAA-related death was not significantly
      different between patients with and without a type 2 endoleak (P = .78). When
      evaluating patients with no early endoleak vs persistent endoleak, freedom from
      sac expansion at 1, 3, and 5 years was 99.2%, 97.6%, and 94.9% (no leak) vs
      88.1%, 48.0%, and 28.0% (persistent) (P < .001). Patients with persistent
      endoleak were at increased risk for aneurysm sac growth vs patients without
      endoleak (odds ratio [OR], 25.9; 95% confidence interval [CI] 11.8 to 57.4; P <
      .001). Patients with a persistent endoleak also had a significantly increased
      rate of reintervention (OR, 19.0; 95% CI, 8.0 to 44.7); P < .001). Finally,
      aneurysm rupture occurred in 4 patients with type 2 endoleaks. Freedom from
      rupture at 1, 3, and 5 years for patients with a persistent type 2 endoleak was
      96.8%, 96.8%, and 91.1% vs 99.8%, 98.5%, and 97.4% for patients without a type 2
      endoleak. Multivariate analysis demonstrated persistent type 2 endoleak to be a
      significant predictor of aneurysm rupture (P = .03). CONCLUSIONS: Persistent type
      2 endoleak is associated with an increased incidence of adverse outcomes,
      including aneurysm sac growth, the need for conversion to open repair,
      reintervention rate, and rupture. These data suggest that patients with
      persistent type 2 endoleak (>6 months) should be considered for more frequent
      follow-up or a more aggressive approach to reintervention.

PMID- 17543490
TI  - Evaluation of the efficacy of the transposed upper arm arteriovenous fistula: a
      single institutional review of 190 basilic and cephalic vein transposition
      procedures.
AB  - INTRODUCTION: Although autogenous brachial-basilic upper arm transpositions (BVT)
      have been extensively utilized, there has been significant disparity in published
      patency rates. Very little is known about the efficacy of autogenous brachial
      cephalic upper arm transpositions (CVT). We evaluated our experience with
      transposed upper arm arteriovenous fistulas (tAVF) in order to assess patency and
      identify factors that affect efficacy. We then compared our tAVF patients with a
      cohort of upper arm arteriovenous grafts (AVG). METHODS: A retrospective review
      was conducted of tAVF performed at our institution from 1998 to 2004. The tAVF
      group consisted of 119 BVT and 71 CVT procedures. We compared these with 164 AVG.
      tAVF were placed only for veins >/=2.5 mm in diameter by duplex ultrasonography.
      RESULTS: Mean follow-up was 28 months. With the exception of mean vein diameter,
      the patients in the BVT and CVT groups had similar demographic parameters and
      complication rates. Primary and secondary patency rates were 52% and 62% at 5
      years for BVT and 40% and 46% at 5 years for CVT, respectively (P = NS).
      Multivariate analysis revealed that hemodialysis dependence at the time of
      fistula placement and history of previous upper arm access independently affected
      primary patency. History of upper torso dialysis catheters independently affected
      secondary patency. Comparison of the tAVF and AVG groups revealed that tAVF
      patients were significantly younger, more likely to be male, less likely to be
      African American (AA) and less likely to have a history of previous AV access.
      The primary patency rate for tAVF was significantly higher than for AVG: 48% vs
      14% at 5 years (P < .001). The secondary patency rate for tAVF was also
      significantly higher than for AVG: 57% vs 17% at 5 years (P < .001). Among the
      tAVF procedures, 9% required one or more revisions to maintain secondary patency,
      compared to 51% with the AVG group (P < .001). Multivariate analysis revealed
      that presence of AVG and a history of previous upper arm access negatively
      affected primary and secondary patency. CONCLUSIONS: Autogenous BVT and CVT have
      similar, high patency rates. Transposed upper arm arteriovenous fistulas have
      higher patency rates than upper arm AVG and require significantly fewer
      revisions. Our data strongly support the contention that as long as the patient
      is a candidate for an upper arm tAVF, based on anatomical criteria, a tAVF should
      always be considered before an AVG.

PMID- 17543491
TI  - Frequency of transient ipsilateral vocal cord paralysis in patients undergoing
      carotid endarterectomy under local anesthesia.
AB  - BACKGROUND: Especially because of improvements in clinical neurologic monitoring,
      carotid endarterectomy done under local anesthesia has become the technique of
      choice in several centers. Temporary ipsilateral vocal nerve palsies due to local
      anesthetics have been described, however. Such complications are most important
      in situations where there is a pre-existing contralateral paralysis. We therefore
      examined the effect of local anesthesia on vocal cord function to better
      understand its possible consequences. METHODS: This prospective study included 28
      patients undergoing carotid endarterectomy under local anesthesia. Vocal cord
      function was evaluated before, during, and after surgery (postoperative day 1)
      using flexible laryngoscopy. Anesthesia was performed by injecting 20 to 40 mL of
      a mixture of long-acting (ropivacaine) and short-acting (prilocaine) anesthetic.
      RESULTS: All patients had normal vocal cord function preoperatively. Twelve
      patients (43%) were found to have intraoperative ipsilateral vocal cord
      paralysis. It resolved in all cases < or =24 hours. There were no significant
      differences in operating time or volume or frequency of anesthetic administration
      in patients with temporary vocal cord paralysis compared with those without.
      CONCLUSION: Local anesthesia led to temporary ipsilateral vocal cord paralysis in
      almost half of these patients. Because pre-existing paralysis is of a relevant
      frequency (up to 3%), a preoperative evaluation of vocal cord function before
      carotid endarterectomy under local anesthesia is recommended to avoid
      intraoperative bilateral paralysis. In patients with preoperative contralateral
      vocal cord paralysis, surgery under general anesthesia should be considered.

PMID- 17543492
TI  - Carotid intraplaque hemorrhage detected by magnetic resonance imaging predicts
      embolization during carotid endarterectomy.
AB  - BACKGROUND: Microembolization detected during the dissection phase of carotid
      endarterectomy (CEA) is associated with plaque instability and might be
      associated with perioperative morbidity. Intraplaque hemorrhage is found in
      unstable plaques and is detectable using magnetic resonance imaging (MRI). We
      aimed to ascertain whether intraplaque hemorrhage as seen on carotid MRI predicts
      particulate embolization in the dissection phase of CEA. METHODS: Patients with
      high-grade symptomatic carotid stenosis undergoing CEA were prospectively
      enrolled. All underwent preoperative MRI assessment of the carotid arteries for
      intraplaque hemorrhage and transcranial Doppler scanning during the dissection
      phase of the CEA to assess the presence of microembolic signals. Associations
      between intraplaque hemorrhage and intraoperative microembolic signals were
      studied. RESULTS: Analysis was undertaken on 60 participants; of these, 36 (60%)
      showed ipsilateral carotid MRI intraplaque hemorrhage, and 24 (40%) did not.
      Microembolic signals were detected during the dissection phase in 23 (38.3%)
      participants, and 19 had MRI-detected intraplaque hemorrhage. The association
      between carotid intraplaque hemorrhage and the presence of dissection phase
      microembolic signals was significant (odds ratio [OR], 5.6; 95% confidence
      interval [CI], 1.6 to 19.7, P = .007), even after controlling for age, sex,
      individual surgeon, degree of stenosis, and delay from symptom to CEA (adjusted
      OR, 5.8; 95% CI, 1.1 to 30.4, P = .037). CONCLUSION: Intraplaque hemorrhage as
      detected by carotid MRI predicts particulate embolization during the dissection
      phase of CEA. This imaging technique can be used to identify patients with
      increased intraoperative thromboembolic risk, and this could influence preventive
      strategies.

PMID- 17543493
TI  - [An unrecognized oesophageal rupture].
AB  - Perforation of the abdominal oesophagus from blunt trauma is an extremely rare
      injury. We report a case of an initially unrecognized oesophageal injury. The
      patient underwent an immediate laparotomy for haemorrhagic shock. The diagnosis
      was made by tomodensitometry and was delayed by modified radiological
      interpretation secondary to laparotomy. Finally, the outcome was favourable.

PMID- 17543494
TI  - [Continuous peripheral regional analgesia in children].
AB  - Continuous peripheral nerve blocks (CPNB) have important role in the therapeutic
      arsenal, anaesthetic or analgesic in children. Indications for CPNB depend on
      benefits/risks analysis for each patient. The indications include surgery
      associated with intense postoperative pain, surgery requiring painful physical
      therapy, and complex regional pain syndrome. CPNB are usually performed under
      sedation or general anaesthesia, and require appropriate equipment in order to
      decrease the risk of nerve injury. Nevertheless, CPNB may mask compartment
      syndrome in trauma or certain surgical procedure. Finally, ropivacaine, and
      perhaps levobupivacaine, appears to be the best local anaesthetic for continuous
      peripheral nerve blocks in children, requiring low flow rate with low
      concentration.

PMID- 17543495
TI  - Taking "existential" suffering seriously.

PMID- 17543496
TI  - To sedate or not to sedate?

PMID- 17543497
TI  - Five-day intensive treatment for adolescent OCD: a case series.
AB  - This case series describes the use of an intensive 5-day treatment for obsessive
      compulsive disorder (OCD) with three adolescents. The treatment is based on
      traditional cognitive-behavioral therapy consisting primarily of exposures and
      response prevention (ERP) and involves 10 sessions over 5 days. In addition, the
      treatment emphasizes instructing the adolescent and the parents on how to conduct
      ERP at home following the completion of the 5 days of therapy. The treatment is
      designed for adolescents who do not have local access to mental health
      practitioners with expertise in ERP for OCD. The three patients who participated
      in the experimental program each experienced substantial improvements in their
      OCD symptoms and overall functioning. The present study suggests that brief, 5
      day intensive treatment may be an effective means of delivering CBT for
      adolescents with OCD and may be of use to mental health practitioners who provide
      services to large catchments.

PMID- 17543498
TI  - A revised nomenclature for the human and rodent alpha-tubulin gene family.
AB  - An essential component of microtubules, alpha-tubulin is also a multigene family
      in many species. An orthology-based nomenclature for this gene family has
      previously been difficult to assign due to incomplete genome builds and the high
      degree of sequence similarity between members of this family. Using the current
      genome builds, sequence analysis of human, mouse, and rat alpha-tubulin genes has
      enabled an updated nomenclature to be generated. This revised nomenclature
      provides a unified language for the discussion of these genes in mammalian
      species; it has been approved by the gene nomenclature committees of the three
      species and is supported by researchers in the field.

PMID- 17543499
TI  - Cancer-related fatigue: links with inflammation in cancer patients and survivors.
AB  - Fatigue is one of the most common and distressing side effects of cancer and its
      treatment and may persist long after successful treatment completion. Emerging
      evidence suggests that inflammatory processes may be involved in cancer-related
      fatigue both during and after treatment. In this review, we consider the evidence
      for an association between inflammation and fatigue in cancer patients and
      survivors. Further, we identify potential mechanisms for persistent inflammation,
      focusing on the HPA axis. Risk factors and treatments for cancer-related fatigue
      are also discussed.

PMID- 17543500
TI  - Activation of NF-kappaB by IL-1beta blocks IL-6-induced sustained STAT3
      activation and STAT3-dependent gene expression of the human gamma-fibrinogen
      gene.
AB  - Despite the essential role of the fibrinogen gamma-chain as a blood clotting
      factor, the fibrinogen gamma-chain contains a number of interaction sites to
      recruit other factors such as leukocytes important for prevention of pathogen
      entry and propagation of the repair process. Interleukin-6 (IL-6) is known as the
      major inducer of gamma-fibrinogen synthesis in hepatocytes, whereas IL-1beta has
      been shown to act as a potent inhibitor of gamma-fibrinogen expression. Studies
      on the rat fibrinogen gamma-chain promoter suggest that nuclear factor (NF)
      kappaB replaces the signal transducer and activator of transcription (STAT) 3
      from binding to overlapping NF-kappaB/STAT3 binding sites within the 5'
      regulatory region of the rat gamma-chain gene promoter. However, despite its
      physiological relevance, the underlying mechanism responsible for the inhibitory
      effect of IL-1beta in humans is still not understood and apparently more complex.
      In contrast to the mechanism described for the rat gene our results indicate that
      IL-1beta suppresses the IL-6-induced activation of the human gamma-fibrinogen
      gene particularly by blocking the late phase STAT3-tyrosine phosphorylation NF
      kappaB-dependently but independent from de novo protein synthesis. Consequently,
      blocking NF-kappaB activation restores specifically late phase STAT3 activation
      as well as the induction of the human gamma-fibrinogen gene. In contrast,
      specifically early STAT3 activation could be restored by a block of the p38
      mitogen-activated protein kinase (p38(MAPK)) pathway. In summary, our results
      indicate that expression of the gamma-fibrinogen gene is mainly controlled by the
      strength of late phase STAT3 activation, which in turn is negatively regulated by
      the extent of IL-1beta-mediated NF-kappaB activity.

PMID- 17543501
TI  - Rates of avoidant, schizotypal, schizoid and paranoid personality disorders in
      psychometric high-risk groups at 5-year follow-up.

PMID- 17543502
TI  - Relation of neurological soft signs to psychiatric symptoms in schizophrenia.
AB  - INTRODUCTION: Although several studies have identified abnormal rates of
      neurological soft signs (NSS) as a manifestation of CNS dysfunction in
      schizophrenia, differences in sample populations have contributed to a
      discrepancy in empirical findings. Furthermore, little is known about the
      potential of NSS to predict a clinical response to antipsychotic medications. The
      present study tests the associations between NSS and schizophrenia symptomatology
      and examines NSS as a potential marker for predicting treatment response.
      METHODS: Nineteen unmedicated male schizophrenia patients were treated
      prospectively with haloperidol for six weeks. The subjects were assessed for pre
      and post-treatment NSS and schizophrenia symptomatology (Brief Psychiatric Rating
      Scale, BPRS). RESULTS: NSS at baseline were significantly associated with
      baseline symptoms on the Positive, Negative, and Psychological Discomfort BPRS
      subscales. NSS showed a strong trend toward improvement during six weeks of a
      prospective haloperidol trial. Hierarchical linear regression analyses indicated
      that more severe baseline NSS predicted poorer response to haloperidol treatment
      as measured by post-treatment BPRS Total subscale scores. DISCUSSION: NSS at
      untreated baseline are associated with baseline symptom severity, and elevated
      NSS are predictive of a smaller degree of improvement in symptoms after
      antipsychotic treatment. These findings are consistent with the hypothesis that
      NSS are linked to the neuropathology that underlies schizophrenia symptomatology
      and course.

PMID- 17543503
TI  - Antimicrobial susceptibility phenotypes, resistance determinants and DNA
      fingerprints of Salmonella enterica serotype Typhimurium isolated from bovine in
      Southern Japan.
AB  - A longitudinal study was conducted in cattle to determine the antimicrobial
      resistance phenotypes, integron elements, resistance genes and pulsed-field gel
      electrophoresis fingerprints among Salmonella enterica serotype Typhimurium
      isolates. A total of 33 strains were isolated and categorised into Groups A, B
      and C during the period 1989-2004. Thirty-one strains (93.9%) showed resistance
      to ampicillin (A) encoded by bla(OXA-1), bla(TEM) and bla(PSE-1) genes; 84.8%
      showed resistance to chloramphenicol (C) encoded by floR and catA1; 97.0% were
      resistant both to streptomycin (S) and sulfamethoxazole (Su), the former encoded
      by aadA1 and aadA2; 100% were resistant to oxytetracycline (T) encoded by tetA,
      tetB and tetG; and 42.4% were resistant to kanamycin (Km) encoded by aphA1-Iab.
      Multidrug resistance types observed were ACSSuT-Km (n=13), ACSSuT (n=15), ASSuT
      (n=3) and SSuT (n=2). Class 1 integrons ranging from 1.0 kb to 1.9 kb were
      detected from 54.5% of isolates (18/33). Integrons were not detected initially
      (1989-1992), then during the 1993-1996 interval a high frequency of 1.0 kb and
      1.2kb amplicons were detected and during 2000-2004 the amplicon size increased to
      1.7 kb and 1.9 kb. We report evidence of additional integration of resistance
      gene cassettes as shown by integrons with increased size. Finally, group B
      strains showed banding patterns indistinguishable from S. Typhimurium DT104
      reference strain, indicating that the DT104 lineage existed on the island since
      1993.

PMID- 17543504
TI  - Characterisation of levofloxacin-resistant clinical isolates of Streptococcus
      pyogenes in Bilbao, Spain.
AB  - The resistance mechanisms and clonal relationship were determined for two
      Streptococcus pyogenes isolates with high-level resistance to levofloxacin as
      well as to other fluoroquinolones. DNA amplification and sequencing revealed a
      serine-81-->phenylalanine substitution in GyrA and a double substitution in ParC
      of serine-79-->phenylalanine and aspartic acid-91-->asparagine. Pulsed-field gel
      electrophoresis analysis and emm typing determined that both isolates were emm
      type 28 and were genetically indistinguishable.

PMID- 17543505
TI  - Effect of olanzapine or risperidone treatment on some cognitive functions in a
      one-year follow-up of schizophrenia outpatients with prominent negative symptoms.
AB  - AIMS: To compare olanzapine and risperidone outcome on some neurocognitive
      dimensions in chronic schizophrenia patients with prominent negative symptoms.
      METHOD: We randomised and followed for 1 year 235 chronic schizophrenia
      outpatients with a SANS global score > or =10 to open-label flexible-dose
      treatment with olanzapine or risperidone. Clinical, functional and cognitive
      assessments [including the COGLAB battery reaction time, vigilance-span of
      apprehension (VSA) and a card-sorting task] were done periodically. RESULTS:
      There were no significant differences between olanzapine (n=120) and risperidone
      (n=115) treatments in the neurocognitive dimensions tested. Mean+/-SD doses were
      12.2+/-5.8 mg/day of olanzapine and 4.9+/-2.0 mg/day of risperidone. Patients in
      the olanzapine group showed a significant improvement in the VSA total score, but
      the within-group change was modest (effect size of 0.26); the difference with the
      risperidone group was not significant (p=0.207). Patients in both groups showed a
      significant improvement in a composite measure of executive efficiency based on
      the card-sorting task, with within-group effect size of 0.21 (risperidone) and
      0.35 (olanzapine); the between-group difference was not significant (p=0.164). At
      baseline, better functional status correlated with VSA. Patients scoring lower on
      VSA or executive efficiency at baseline improved more on these respective
      measures. CONCLUSION: Modest pro-cognitive effects can also be found in chronic
      schizophrenia outpatients with prominent negative symptoms when treated with
      olanzapine or risperidone.

PMID- 17543506
TI  - Drosophila Dystrophin is required for integrity of the musculature.
AB  - Duchenne muscular dystrophy is caused by mutations in the dystrophin gene and is
      characterized by progressive muscle wasting. The highly conserved dystrophin gene
      encodes a number of protein isoforms. The Dystrophin protein is part of a large
      protein assembly, the Dystrophin glycoprotein complex, which stabilizes the
      muscle membrane during contraction and acts as a scaffold for signaling
      molecules. How the absence of Dystrophin results in the onset of muscular
      dystrophy remains unclear. Here, we have used transgenic RNA interference to
      examine the roles of the Drosophila Dystrophin isoforms in muscle. We previously
      reported that one of the Drosophila Dystrophin orthologs, the DLP2 isoform, is
      not required to maintain muscle integrity, but plays a role in neuromuscular
      homeostasis by regulating neurotransmitter release. In this report, we show that
      reduction of all Dystrophin isoform expression levels in the musculature does not
      apparently affect myogenesis or muscle attachment, but results in progressive
      muscle degeneration in larvae and adult flies. We find that a recently identified
      Dystrophin isoform, Dp117, is expressed in the musculature and is required for
      muscle integrity. Muscle fibers with reduced levels of Dp117 display disorganized
      actin-myosin filaments and the cellular hallmarks of necrosis. Our results
      indicate the existence of at least two possibly separate roles of dystrophin in
      muscle, maintaining synaptic homeostasis and preserving the structural stability
      of the muscle.

PMID- 17543507
TI  - Adhesion characteristics of two Burkholderia cepacia strains examined using
      colloid probe microscopy and gradient force analysis.
AB  - Colloid probe atomic force microscopy (CP-AFM) was used to investigate two
      strains of Burkholderia cepacia in order to determine what molecular scale
      characteristics of strain Env435 make it less adhesive to surfaces than the
      parent strain, G4. CP-AFM approach curves analyzed using a gradient force method
      showed that in a high ionic strength solution (IS=100 mM, Debye length=1 nm), the
      colloid probe was attracted to the surface of strain G4 at a distance of
      approximately 30 nm, but it was repelled over a distance of 25 nm when
      approaching strain Env435. Adhesion forces measured under the same solution
      conditions during colloid retraction showed that 1.38 nN of force was required to
      remove the colloid placed in contact with the surface of strain G4, whereas only
      0.58 nN was required using strain Env435. At IS=1mM (Debye length=10nm), the
      attractive force observed with G4 was no longer present, and the repulsive force
      seen with Env435 was extended to approximately 250 nm. The adhesion of the
      bacteria to the probe was much less at low IS solution (1 mM) than at high IS
      (100 mM). The greater adhesion characteristics of strain G4 compared to Env435
      were confirmed in column tests. Strain G4 had a collision efficiency of
      alpha=0.68, while strain Env435 had a much lower collision efficiency of
      alpha=0.01 (IS=100 mM). These results suggest that the reduced adhesion of strain
      Env435 measured in column tests is due to the presence of high molecular weight
      extracellular polymeric substances that extend out from the cell surface,
      creating long-range steric repulsion between the cell and a surface. Adhesion is
      reduced as these polymers do not appear to be "sticky" when placed in contact
      with a surface in AFM tests.

PMID- 17543508
TI  - [A rare complication after surgery of Hirschsprung disease: perianal
      papulonodular dermatitis].

PMID- 17543509
TI  - [Opsoclonus-myoclonus syndrome associated with Mycoplasma pneumoniae infection].
AB  - Mycoplasma pneumoniae infection is associated with various manifestations
      involving the central nervous system but it has never been reported as a
      potential aetiology of opsoclonus-myoclonus syndrome (OMS) in children.
      OBSERVATION: We report on a case in a 4-year-old girl who presented neurological
      manifestations compatible with an OMS, after a respiratory tract disease.
      Aetiological investigations revealed M. pneumoniae infection as specific IgM were
      present in the serum (Elisa). Evolution after corticosteroid, intravenous
      immunoglobulins and macrolide therapy was favourable as clinical symptoms
      disappeared. After a 12-month follow-up, the patient has no neurological sequela.
      CONCLUSION: M. pneumoniae infection should be added to the list of causes to be
      screened in OMS. Its pathophysiology remains unknown but may involve a dysimmune
      postinfectious mechanism.

PMID- 17543510
TI  - [Autosomal recessive renal tubular dysgenesis: morphologic and genetic study of 2
      cases].
AB  - Renal tubular dysgenesis (RTD) is a rare and severe nephropathy characterized by
      persistent fetal anuria leading to oligohydramnios with the Potter sequence, and
      perinatal death. The diagnosis is based on the histological finding of absence or
      paucity of proximal tubules. A consanguineous family is described in which 2
      siblings, born after pregnancies complicated by oligohydramnios were affected
      with RTD. Patients were small for gestational age at birth. The first patient
      died after a few hours, the second after a few days of life, with persistent
      anuria unresponsive to treatment. Histologically, there was marked reduction in
      the number of proximal tubule sections and no renin was detected by
      immunohistochemistry. An homozygous mutation of the gene encoding renin was
      identified in both patients. This study underlines the interest of the
      histological examination of the kidney for the diagnostic of RTD in anuric
      fetuses and newborns, and the possibility of mutation analysis of RAS genes for
      genetic counselling and early prenatal diagnosis.

PMID- 17543511
TI  - [Drugs news].

PMID- 17543512
TI  - A methodology for the automated creation of fuzzy expert systems for ischaemic
      and arrhythmic beat classification based on a set of rules obtained by a decision
      tree.
AB  - OBJECTIVE: In the current work we propose a methodology for the automated
      creation of fuzzy expert systems, applied in ischaemic and arrhythmic beat
      classification. METHODS: The proposed methodology automatically creates a fuzzy
      expert system from an initial training dataset. The approach consists of three
      stages: (a) extraction of a crisp set of rules from a decision tree induced from
      the training dataset, (b) transformation of the crisp set of rules into a fuzzy
      model and (c) optimization of the fuzzy model's parameters using global
      optimization. MATERIAL: The above methodology is employed in order to create
      fuzzy expert systems for ischaemic and arrhythmic beat classification in ECG
      recordings. The fuzzy expert system for ischaemic beat detection is evaluated in
      a cardiac beat dataset that was constructed using recordings from the European
      Society of Cardiology ST-T database. The arrhythmic beat classification fuzzy
      expert system is evaluated using the MIT-BIH arrhythmia database. RESULTS: The
      fuzzy expert system for ischaemic beat classification reported 91% sensitivity
      and 92% specificity. The arrhythmic beat classification fuzzy expert system
      reported 96% average sensitivity and 99% average specificity for all categories.
      CONCLUSION: The proposed methodology provides high accuracy and the ability to
      interpret the decisions made. The fuzzy expert systems for ischaemic and
      arrhythmic beat classification compare well with previously reported results,
      indicating that they could be part of an overall clinical system for ECG analysis
      and diagnosis.

PMID- 17543513
TI  - Effect of formulation parameters on the release characteristics of propranolol
      from asymmetric membrane coated tablets.
AB  - Controlled delivery of drugs has been achieved successfully by use of asymmetric
      membranes. In our study, we have evaluated the influence of various preparation
      parameters such as concentration of the polymer, concentration of the pore former
      and temperature of the precipitation bath on the permeability and the release
      characteristics of propranolol. Propranolol tablets were prepared by direct
      compression and were coated with varying concentrations of cellulose acetate and
      glycerin. The coat was precipitated in water, maintained at various temperatures,
      followed by air drying of the coat. Scanning Electron Microscopy (SEM) was used
      to characterize the asymmetric structure of the membrane. The influence of
      various preparation parameters on the release of propranolol from asymmetric
      coated tablets was evaluated. SEM confirmed the asymmetric nature of the
      membrane. A zero order release of propranolol was obtained from the coated
      tablets of propranolol. Various preparation parameters studied significantly
      affected (p<0.05) the release of propranolol hydrochloride from the asymmetric
      membrane coated tablets and the release was independent of the pH and the rate of
      agitation of the dissolution medium (p>0.05). Asymmetric membranes can be
      successfully utilized in the controlled delivery of highly water soluble drugs
      like propranolol and by modifying preparation parameters like polymer
      concentration, pore former concentration and temperature of the precipitation
      bath, desired release rates can be obtained.

PMID- 17543514
TI  - Picogram detection of metal ions by melanin-sensitized piezoelectric sensor.
AB  - A heavy metal ion sensor was constructed by cross-linking melanin onto the gold
      electrode of quartz crystal microbalance (QCM). A mercury ion sensitivity of
      518+/-37 Hz/ppm was observed, a substantial increase in sensitivity compared to
      previous reports of 10-50 Hz/ppm with the limit of detection at 5 ppb. Detection
      of other metal ions including Sn(2+), Ge(4+), Li(+), Zn(2+), Cu(2+), Bi(3+),
      Co(2+), Al(3+), Ni(2+), Ag(+), and Fe(3+) were also performed. Unexpectedly,
      binding of Mn(7+), Pb(2+), Cd(2+), and Cr(3+) increased resonant frequencies. The
      surface profile of melanin thin film upon binding to metal ions was investigated
      by atomic force microscopy (AFM). Structural change of melanin upon binding to
      metal ions was characterized by circular dichroism and by infrared spectroscopy.
      The current study provides the first example of melanin-coated piezoelectric
      sensor showing high sensitivity and selectivity to metal ions.

PMID- 17543515
TI  - A review of long-term follow-up for survivors of childhood cancer.
AB  - Though cure from cancer is not guaranteed, children's chances of survival have
      increased significantly. As a result the paediatric oncology community is focused
      on providing appropriate follow-up care to an increasing number of young cancer
      survivors. How this care should be designed and delivered however remains the
      centre of ongoing discussion and was the focus of this review. The aims of the
      review were to (1) gain an understanding of current follow-up practices from
      studies involving health care professionals, (2) identify and evaluate studies
      presenting views of survivors, (3) examine commentaries on both the current and
      future design of long-term follow-up services and (4) evaluate existing follow-up
      guidelines. Empirical research, commentary papers and published guidelines were
      reviewed. Twenty-eight papers and five guidelines were analysed. Empirical papers
      were examined in relation to sample, design, findings and limitations. Commentary
      papers were assessed in relation to key issues about follow-up care. Guidelines
      were assessed on how far they were evidence-based, peer-reviewed and involved
      users in their development. Varying models of care were illustrated, and were
      dependent upon personnel and centre orientation. Variability in the level and
      degree to which long-term survivors were followed up was also reported.
      Inconsistencies in practice were noted. Nonetheless requirements for an effective
      service were highlighted in the majority of publications, these included
      communication and information. Although young people and professionals had a
      shared view on many aspects of follow-up care, these preferences were not
      consistently mirrored in service provision.

PMID- 17543516
TI  - Retinoblastoma epidemiology: does the evidence matter?
AB  - It has been proposed that retinoblastoma is 'caused' by two sequential mutations
      affecting the RB1 gene, but this is a rather outdated view of cancer aetiology
      that does not take into account a large amount of new acquisitions such as
      chromosomal and epigenetic alterations. Retinoblastoma remains probably the only
      cancer in which the rather simplistic 'two hit' mutational model is still
      considered of value, although cancer is known to be associated with genomic and
      microsatellite instability, defects of the DNA mismatch repair system,
      alterations of DNA methylation and hystone acethylation/deacethylation, and
      aneuploidy. Moreover, as it is shown herein, the predictions made by the 'two
      hit' model, are not fulfilled by the clinical and epidemiological data reported
      so far. Moreover, while the role of mutational events in cancer has been largely
      questioned in the more recent literature, no serious effort has been done to
      investigate the role of epigenetic alterations and aneuploidy in retinoblastoma.
      Through the analysis of the specialised literature and a set of original
      epidemiological and biological data concerning retinoblastoma, the authors
      illustrate the evidences arguing against the 'two hit' hypothesis and propose
      that epigenetic factors and aneuploidy play central roles in the disease.

PMID- 17543517
TI  - Long term survivors of childhood cancer: cure and care. The Erice statement.
AB  - The number of subjects that have successfully completed treatment for a cancer
      diagnosed during childhood and are entering adulthood is increasing over time.
      Members of the International Berlin-Frankfurt-Munster (I-BFM) Early and Late
      Toxicity Educational Committee (ELTEC) invited 45 paediatric cancer experts
      (representing oncologists, psychologists, nurses, epidemiologists, parents, and
      survivors) from 13 European countries (with five additional experts from North
      America) to Erice, Sicily (from October 27 to 29, 2006) to discuss the
      circumstances in which the word 'cure' should be used when speaking about
      children with cancer, and when and why continuing follow-up and care may be
      required. The objective of the gathering was to generate from the personal and
      professional experience of the participants an overview statement of the group's
      philosophy of cure and care of survivors of childhood cancer. The ten points
      reflect what the group considers essential in the survivors' cure and care.

PMID- 17543518
TI  - Ensiling olive cake with and without molasses for ruminant feeding.
AB  - The purpose of the current experiment was to study the ensiling properties of
      olive cake with and without added molasses at 2-6% (w/w). The results indicate
      that molasses enhanced the ensiling fermentation of olive cake, as evidenced from
      higher lactic acid content and higher lactic acid bacteria numbers at 4% and 6%
      added molasses. However, when applied at 4% and 6% molasses increased
      fermentation losses up to 9.4%, probably due to larger yeast population.
      Polyphenols which could interfere with protein utilization by ruminants,
      decreased during ensiling by about 40%. It is concluded that molasses added at 3%
      could improve the ensiling fermentation of olive cake without substantial losses.

PMID- 17543519
TI  - Utilization of ground eggshell waste as an adsorbent for the removal of dyes from
      aqueous solution.
AB  - The adsorption of cationic basic blue 9 and anionic acid orange 51 from aqueous
      solution onto the calcified eggshell (ES) and its ground eggshell powder (ESP)
      was carried out by varying the process parameters such as agitation speed,
      initial dye concentration, adsorbent mass and temperature. The adsorption
      potential for basic blue 9 onto ESP is far lower than that for acid orange 51,
      mainly due to the ionic interaction between the acid dye with the sulfonate
      groups and the positively charged sites on the surface of ESP. The adsorption
      capacity of acid orange 51 onto ES is significantly smaller than that onto ESP,
      which is in line with their pore properties (i.e., 1 vs. 21 m(2)/g). The
      experimental results showed that the adsorption process can be well described
      with a simple model, the pseudo-second-order model. According to the equilibrium
      adsorption capacity from the fitting of pseudo-second order reaction model, it
      was further found that the Freundlich model yields a somewhat better fit than the
      Langmuir model in the adsorption of acid orange 51 onto ESP. In addition, an
      increase in adsorption temperature from 15 to 45 degrees C significantly enhances
      the adsorption capacity of acid orange 51 onto ESP, revealing that the adsorption
      should be an endothermic or chemisorption process. From the results, it is
      feasible to utilize the ground eggshell waste as an effective adsorbent for
      removal of anionic dye from aqueous solution.

PMID- 17543520
TI  - Lipolytic activity of suspended and membrane immobilized lipase originating from
      indigenous Burkholderia sp. C20.
AB  - In this work, a simple, inexpensive, and efficient method of preparing
      immobilized lipase is presented. The lipase originating from a newly isolated
      indigenous strain Burkholderia sp. C20 was immobilized onto cellulose nitrate
      (CN) membrane via filtration. The CN-immobilized lipase was able to retain 60% of
      its original activity after repeated uses for nine times. The thermal stability
      of the lipase was also slightly improved after immobilization. The optimal
      reaction conditions of CN-lipase were pH 9.0 and 55 degrees C, which are similar
      to those for the suspended lipase. Both suspended and immobilized lipase could
      hydrolyze the six oil substrates examined, while immobilized lipase displayed
      less specificity over the oil substrates. Kinetic analysis shows that the
      dependence of lipolytic activity of both suspended and immobilized lipase on oil
      substrate concentration can be described by Michaelis-Menten model with good
      agreement. The estimated kinetic constants for suspended lipase (v(max)=243.9
      U/mg, K(m)=0.024 mM) and immobilized lipase (v(max)=32.8 U/mg, K(m)=5.61 mM) were
      quite different. Employment of immobilization seemed to result in a decrease in
      v(max) and an increase in K(m), most likely due to the mass transfer resistance
      arising from formation of micelles during the lipase immobilization process.

PMID- 17543521
TI  - Discovery of inhibitors of the pentein superfamily protein dimethylarginine
      dimethylaminohydrolase (DDAH), by virtual screening and hit analysis.
AB  - An efficient process for the discovery of inhibitors of DDAH enzymes, without the
      requirement for high throughput screening, is described. Physicochemical
      filtering of a 308,000-compound library according to drug likeness followed by
      reciprocal nearest neighbour selection produced a representative subset of 35,000
      compounds. Virtual screening on a dual processor PC using FlexX, followed by
      biological screening, identified two hit series. Similarity searches of
      commercial databases and chemical re-synthesis of pure compounds resulted in
      SR445 as an inhibitor of Pseudomonas aeruginosa DDAH at 2 microM.

PMID- 17543522
TI  - Ortho-azo substituted phenylboronic acids for colorimetric sugar sensors.
AB  - The phenylboronic acids substituted with an azo group on the ortho-position show
      a significant change in UV-vis spectra upon sugar binding. A new mechanism for
      the spectral change of the dyes is proposed based on the formation and cleavage
      of B-N dative bond between boronic acid group and azo group.

PMID- 17543523
TI  - R-(-)-N-alkyl-11-hydroxy-10-hydroxymethyl- and 10-methyl-aporphines as 5-HT1A
      receptor ligands.
AB  - Several N-substituted-11-hydroxy-10-hydroxymethyl- and 11-hydroxy-10
      methylaporphines were synthesized and their binding affinities at dopamine D(1)
      and D(2) receptors and serotonin 5-HT(1A) and 5-HT(2A) receptors in rat forebrain
      tissue were evaluated. Tested compounds displayed moderate to high affinity to 5
      HT(1A) receptors but low affinity to D(1) and D(2) receptors. The most potent
      novel 5-HT(1A) agent was R-(-)-N-methyl-10-hydroxymethyl-11-hydroxyaporphine.

PMID- 17543524
TI  - Thyroid receptor ligands. Part 8: Thyromimetics derived from N-acylated-alpha
      amino acid derivatives displaying modulated pharmacological selectivity compared
      with KB-141.
AB  - Based on the scaffold of the pharmacologically selective thyromimetic 2b,
      structurally a close analog to KB-141 (2a), a number of novel N-acylated-alpha
      amino acid derivatives were synthesized and tested in a TR radioligand binding
      assay as well as in a reporter cell assay. On the basis of TRbeta(1)-isoform
      selectivity and affinity, as well as affinity to the reporter cell assay, 3d was
      selected for further studies in the cholesterol-fed rat model. In this model 3d
      revealed an improved therapeutic window between cholesterol and TSH lowering but
      decreased margins versus tachycardia compared with 2a.

PMID- 17543525
TI  - Natural feruloyl monoglyceride macrocycles as protecting factors against free
      radical damage of lipidic membranes.
AB  - Nine novel natural feruloyl monoglyceride (MGs) macrocycles have been isolated
      from the leaves of Carex distachya, an herbaceous plant growing in the
      Mediterranean maquis. All the structures have been elucidated on the basis of
      their spectroscopic features, especially two-dimensional NMR (DQ-COSY, TOCSY,
      NOESY, ROESY, HSQC, HMBC, HSQC-TOCSY) and ESI-MS. All the compounds have been
      assayed as protecting factors against the radical damage of the lipids by using
      different antioxidant tests.

PMID- 17543526
TI  - Synthesis and antitumour activity of new tiazofurin analogues bearing a 2,3
      anhydro functionality in the furanose ring.
AB  - This paper describes a divergent de novo synthesis of 2-(2,3-anhydro-beta
      dribofuranosyl)thiazole-4-carboxamide (2',3'-anhydro-tiazofurin) and the
      corresponding alpha- and beta-homo-C-nucleosides, as well as evaluation of their
      antitumour activities in vitro.

PMID- 17543527
TI  - In vivo acquisition of prophage in Streptococcus pyogenes.
AB  - Genomic analysis of 12 Streptococcus pyogenes genomes representing six different
      serotypes reveals that they are poly-lysogenized, with as many as seven separate
      phage genomes (some of which are defective). Sequence alignments of these genomes
      (excluding incorporated prophage) have revealed that they are approximately 90%
      conserved, indicating that their diversity and disease capacity might be phage
      related. However, because S. pyogenes are only found in humans, how are new
      phages acquired? In vitro and in vivo experiments show that efficient phage
      transfer from donor to recipient streptococci occurs in the presence of mammalian
      cells. This suggests that, through evolution, phage have devised a system whereby
      progeny phage are induced and transferred to host streptococci at a site where
      host organisms are more prevalent.

PMID- 17543528
TI  - Multilevel cervical fusion without plates, screws or autogenous iliac crest bone
      graft.
AB  - OBJECTIVE: This prospective study was performed to evaluate the safety and
      efficacy of polyetheretherketone (PEEK) cages packed with demineralized bone
      matrix (DBM) mixed with autologous blood and curettage microchip material for
      treatment of multilevel cervical disc disease and spondylosis without the use of
      plates, screws or autogenous iliac crest bone graft. MATERIAL AND METHODS:
      Sixteen patients underwent multilevel anterior cervical discectomy and fusion
      (ACDF) for a total of 42 levels. Minimum follow-up was 18 months. Neurological
      outcomes were evaluated using the Japanese Orthopaedic Association (JOA) scoring
      system; cervical lordosis and cervical fusion status was assessed on X-ray.
      Statistical analysis was performed to compare preoperative and postoperative
      scores using a dependent t-test (P<0.05). RESULTS: Eight patients underwent two
      level, six underwent three-level and two underwent four-level operations. The
      fusion rate was 90.5% and non-fusion rate was 9.5%, but reoperation was not
      required for these patients in the follow-up period. Cervical lordosis was
      preserved and neurological status was improved. No cage migration or cage failure
      occured. CONCLUSION: ACDF using PEEK cages packed with DBM is a safe and
      efficient method for treatment of multilevel cervical disc disease and
      spondylosis. It preserves cervical lordosis and obviates the complications
      related to iliac crest graft harvest and screw-plate fixation.

PMID- 17543529
TI  - Experimental image-guided endoscopic pituitary surgery: a useful learning model.
AB  - OBJECTIVES: The purpose of this study, which combined image guidance and
      endocscopic pituitary surgery (EPS), was to test its practicability as a learning
      tool to acquire the necessary skills in an experimental setting. METHODS: Ten
      cadaver-heads were explored using a standard endoscopic transsphenoidal surgical
      technique combined with the InstaTrak 3500 (GE Medical Systems, Lawrence, MA,
      USA) image guidance system. The time taken for the experimental setup and the
      optic-radiologic correlations of topographic landmarks were recorded and
      photographed. RESULTS: The average time for setting up the system was 11.9 min+/
      2.0, which included head fixation, headset positioning, registration, calibration
      and verification of the system. With the guidance of the navigation system, the
      ostium, sellar floor and adjacent structures encountered during EPS could be
      identified easily and were reflected on the 3D-CT images accurately. CONCLUSION:
      The experimental model validated the practicability of image guidance combined
      with EPS. The non-invasive interactive computer-assisted CT-guided navigational
      system facilitated the surgical procedure by providing precise spatial
      relationship between instrument position and adjacent structures. This
      combination is a useful teaching and learning tool in the cadaver and in patients
      will be useful, particularly for complex cases and redo-surgery.

PMID- 17543530
TI  - Ethics in medical technologies.

PMID- 17543531
TI  - Alignment of the femoral component in a mobile-bearing unicompartmental knee
      arthroplasty: a study in 10 cadaver femora.
AB  - Use of an intramedullary rod is advised for the alignment of the femoral
      component of an Oxford phase-III prosthesis. There are users moving toward
      extramedullary alignment, which is merely an indicator of frustration with
      accuracy of intramedullary alignment. The results of our study with 10 cadaver
      femora demonstrate that use of a short and long intramedullary femoral rod may
      result in excessive flexion alignment error of the femoral component.
      Understanding of the extramedullary alignment possibility and experience with the
      visual alignment of the femoral drill guide is essential toward minimizing
      potential errors in the alignment of the femoral component.

PMID- 17543532
TI  - 5-Arylidene-2,4-thiazolidinediones as inhibitors of protein tyrosine
      phosphatases.
AB  - 4-(5-Arylidene-2,4-dioxothiazolidin-3-yl)methylbenzoic acids (2) were synthesized
      and evaluated in vitro as inhibitors of PTP1B and LMW-PTP, two protein tyrosine
      phosphatases (PTPs) which act as negative regulators of the metabolic and mitotic
      signalling of insulin. The synthesis of compounds 2 represents an example of
      utilizing phosphotyrosine-mimetics to identify effective low molecular weight
      nonphosphorus inhibitors of PTPs. Several thiazolidinediones 2 exhibited PTP1B
      inhibitory activity in the low micromolar range with moderate selectivity for
      human PTP1B and IF1 isoform of human LMW-PTP compared with other related PTPs.

PMID- 17543533
TI  - Normal platelet mitochondrial complex I activity in Huntington's disease.
AB  - Two small case series of platelet mitochondrial complex I activity assays in
      Huntington's Disease (HD) report discrepant results. We measured platelet complex
      I and complex I/III activity in 21 subjects with early gene-positive HD and 14
      age-matched controls. The 21 participants with HD that we studied are greater
      than the total of 16 in the two previously published of platelet ETS activity in
      HD. Reductions > 10% were excluded with 80% confidence. A systemic defect in
      complex I activity is not present in early HD when striatal neuronal degeneration
      is already present.

PMID- 17543534
TI  - A study of b1+H2O and b1-ions in the product ion spectra of dipeptides containing
      N-terminal basic amino acid residues.
AB  - The product ion spectra of approximately 200 dipeptides were acquired under low
      energy conditions using a triple quadrupole mass spectrometer. The spectra of
      dipeptides containing an N-terminal arginine (R), histidine (H), or lysine (K)
      were observed to yield a b(1) + H(2)O ion corresponding to the protonated basic
      amino acid. This was equivalent to the y(1)-ion in the corresponding C-terminal
      isomer. The formation of a b(1) + H(2)O ion was not a significant fragmentation
      channel in any dipeptides analyzed including those containing a C-terminal basic
      amino acid unless they also contained an N-terminal basic amino acid. Occurring
      simultaneously and under equal energy conditions an apparent b(1)-ion was formed,
      which has its corresponding C-terminal equivalent in the y(1)-H(2)O ion. Energy
      resolved mass spectrometry (ERMS), deuterium labeling, and accurate mass
      experiments as well as data reported were used to show the relationships between
      the b(1)+H(2)O and b(1)-ions in the dipeptides containing an N-terminal basic
      amino acid and the y(1) and y(1)-H(2)O ions in the corresponding C-terminal
      isomers.

PMID- 17543535
TI  - Factors that impact the vacuum ultraviolet photofragmentation of peptide ions.
AB  - Several groups have investigated the photodissociation of peptide ions with
      ultraviolet light. Significant differences have been reported with 157 and 193 nm
      excitation. Recent studies have shown that the mass analyzer can also influence
      the observed photofragment distribution. Comparison of experiments using
      different peptides, wavelengths, and mass analyzers is undesirably complicated.
      In the present work, several peptides are analyzed with both 157 and 193 nm
      photodissociation in tandem-TOF and linear ion trap mass spectrometers. The
      results indicate that the fragment ion distribution can be influenced by both the
      photodissociation wavelength and the mass analyzer. The two wavelengths generate
      similar spectra in an ion trap but quite different results in a tandem-TOF
      instrument.

PMID- 17543536
TI  - The application of a hypothesis-driven strategy to the sensitive detection and
      location of acetylated lysine residues.
AB  - The application of a hypothesis-driven method for the sensitive determination of
      lysine acetylation sites on enzymatically digested proteins is described.
      Comparative sensitivity tests were carried out using serial dilution of an
      acetylated bovine serum albumin (AcBSA) digest to assess the performance of a
      multiple reaction monitoring (MRM)-based approach as compared to a more
      conventional precursor scanning (PS) method. Both methods were capable of
      selectively detecting an acetylated peptide at the low femtomole level when
      spiked into a background of 500 fmol six-protein tryptic digest. The MRM approach
      was roughly tenfold more sensitive than precursor scanning with one acetylated
      peptide detected and sequenced at the level of 2 fmol on-column. The technique
      was subsequently applied to a gel-derived sample of cytokeratin-8 (CK8) shown to
      contain acetylated lysine residues by Western blot analysis. The strategy applied
      herein, termed MRM-initiated detection and sequencing (MIDAS), resulted in the
      facile identification of novel sites of acetylation on this protein.

PMID- 17543537
TI  - UNC5C is required for spinal accessory motor neuron development.
AB  - In both invertebrates and vertebrates, UNC5 receptors facilitate chemorepulsion
      away from a Netrin source. Unlike most motor neurons in the embryonic vertebrate
      spinal cord, spinal accessory motor neuron (SACMN) cell bodies and their axons
      translocate along a dorsally directed trajectory away from the floor
      plate/ventral midline and toward the lateral exit point (LEP). We have recently
      shown that Netrin-1 and DCC are required for the migration of SACMN cell bodies,
      in vivo. These observations raised the possibility that vertebrate UNC5 proteins
      mediate the presumed repulsion of SACMN away from the Netrin-rich ventral
      midline. Here, we show that SACMN are likely to express UNC5A and UNC5C. Whereas
      SACMN development proceeds normally in UNC5A null mice, many SACMN cell bodies
      fail to migrate away from the ventral midline and inappropriately cluster in the
      ventrolateral spinal cord of mouse embryos lacking UNC5C. These results support
      an important role for UNC5C in SACMN development.

PMID- 17543538
TI  - A combined approach to improving large-scale production of tobacco etch virus
      protease.
AB  - Tobacco etch virus NIa proteinase (TEV protease) is an important tool for the
      removal of fusion tags from recombinant proteins. Production of TEV protease in
      Escherichia coli has been hampered by insolubility and addressed by many
      different strategies. However, the best previous results and newer approaches for
      protein expression have not been combined to test whether further improvements
      are possible. Here, we use a quantitative, high-throughput assay for TEV protease
      activity in cell lysates to evaluate the efficacy of combining several previous
      modifications with new expression hosts and induction methods. Small-scale
      screening, purification and mass spectral analysis showed that TEV protease with
      a C-terminal poly-Arg tag was proteolysed in the cell to remove four of the five
      arginine residues. The truncated form was active and soluble but in contrast, the
      tagged version was also active but considerably less soluble. An engineered TEV
      protease lacking the C-terminal residues 238-242 was then used for further
      expression optimization. From this work, expression of TEV protease at high
      levels and with high solubility was obtained by using auto-induction medium at 37
      degrees C. In combination with the expression work, an automated two-step
      purification protocol was developed that yielded His-tagged TEV protease with
      >99% purity, high catalytic activity and purified yields of approximately 400
      mg/L of expression culture (approximately 15 mg pure TEV protease per gram of E.
      coli cell paste). Methods for producing glutathione-S-transferase-tagged TEV with
      similar yields (approximately 12 mg pure protease fusion per gram of E. coli cell
      paste) are also reported.

PMID- 17543539
TI  - A two-plasmid Escherichia coli system for expression of Dr adhesins.
AB  - This paper presents a very efficient expression system for production of Dr
      adhesins. The system consists of two plasmids. One is the pACYCpBAD-DraC-C-His,
      which contains the draC gene under the control of the arabinose promoter (pBAD),
      encoding the DraC usher. The second is the pET30b-syg-DraBE, which contains the
      draB and draE genes under the control of the T7lac promoter, encoding the DraB
      chaperone and the DraE adhesin, respectively. Those plasmids have different
      origin of replication and can therefore coexist in one cell. Since different
      promoters are present, the protein expression can be controlled. The Dr adhesion
      expression system constructed opens up a lot of possibilities, and could be very
      useful in experiments focusing on understanding the biogenesis of Gram-negative
      bacteria adhesins. For this purpose we showed that the AfaE-III adhesin (98.1%
      identity between the DraE and the AfaE-III adhesins, with three divergent amino
      acids within the sequences) was able to pass through the DraC channel in the
      Escherichia coli BL21(DE3) strain. Immunoblotting analysis and immunofluorescence
      microscopy showed the presence of AfaE-III on the bacterial cell surface. In
      addition, the system described can be useful for displaying the immune-relevant
      sectors of foreign proteins on the bacterial cell. The heterologous epitope
      sequence of the HSV1 glycoprotein D was inserted into the draE gene in place of
      the N-terminal region of surface exposed domain 2. Chimeric proteins were exposed
      on the bacterial surface as evidenced by immunoblotting and immunofluorescence
      microscopy. The effective display of peptide segments on Dr fimbriae expressed at
      the bacterial cell surface, can be used for the development of a fimbrial
      vaccine.

PMID- 17543540
TI  - Yours or mine? Ownership and memory.
AB  - An important function of the self is to identify external objects that are
      potentially personally relevant. We suggest that such objects may be identified
      through mere ownership. Extant research suggests that encoding information in a
      self-relevant context enhances memory (the so-called 'self-reference effect'),
      thus an experiment was designed to test the impact of ownership on memory
      performance. Participants either moved or observed the movement of picture cards
      into two baskets; one of which belonged to self and one which belonged to another
      participant. A subsequent recognition test revealed that there was a significant
      memory advantage for objects that were owned by self. Acting on items (i.e.,
      moving them) had no impact on memory. Results are discussed with reference to the
      importance of self-object associations in cognition.

PMID- 17543541
TI  - Voxel-based analysis of the evolution of magnetization transfer ratio to quantify
      remyelination and demyelination with histopathological validation in a multiple
      sclerosis lesion.
AB  - We present a new method for advanced image processing to separately quantify
      significant decreases and increases in the magnetization transfer ratio (MTR) of
      individual voxels of MS lesions as markers of demyelination and remyelination. We
      used this method to analyze the evolution of MTR in individual voxels of an
      acute, Gadolinium (Gd)-enhancing lesion that was available for pathology. Over
      6.5 months following enhancement, MTR was low and stable in the lesion center
      (81% of the initially Gd-enhancing lesion volume (GdLV)) and MTR increased at the
      lesion border with normal-appearing white matter (14%GdLV). The estimated error
      of these measurements was less than 1.8%GdLV based on scan/rescan analysis.
      Histopathological analysis confirmed a demyelinated lesion centre with diffuse
      presence of macrophages/microglia and marked loss of oligodendrocytes and a
      partially remyelinated lesion border with diffuse presence of
      macrophages/microglia and relatively more oligodendrocytes compared to the lesion
      centre. The correlation of imaging and histopathological findings support the
      validity and sensitivity of our method of voxel-based MTR image processing for
      monitoring demyelination and remyelination in vivo.

PMID- 17543542
TI  - Interhemispheric asymmetry of primary hand representation and recovery after
      stroke: a MEG study.
AB  - In patients affected by monohemispheric stroke in the middle cerebral artery
      territory, who do not regain a normal neurological function, a positive
      contribution to the clinical recovery seems to be made by the involvement of
      primary hand representation areas in the affected hemisphere (AH), excessively
      asymmetric to its homologous in the unaffected hemisphere (UH). We investigated
      primary sensory hand areas in 41 chronic patients who had improved their clinical
      status without reaching complete recovery. The location and strength of the first
      cerebral sources activated by a contralateral galvanic median nerve stimulation
      (M20 and M30) were evaluated in both hemispheres, together with their
      interhemispheric differences. The source displacement in the AH with respect to
      the UH was positively correlated with clinical recovery (Spearman's rho=0.584,
      p=0.003). The excessive interhemispheric asymmetry - as defined on the basis of
      reference ranges in the healthy population - could be interpreted as the
      involvement of neuronal pools in the AH outside the hand 'omega zone' of the
      Rolandic sulcus, revealing the presence of plasticity phenomena. The present data
      provide support to a positive role of cerebral plasticity phenomena, partially
      contributing to post-stroke recovery in patients unable to achieve normal
      neurological function.

PMID- 17543543
TI  - A Bayesian framework for global tractography.
AB  - We readdress the diffusion tractography problem in a global and probabilistic
      manner. Instead of tracking through local orientations, we parameterise the
      connexions between brain regions at a global level, and then infer on global and
      local parameters simultaneously in a Bayesian framework. This approach offers a
      number of important benefits. The global nature of the tractography reduces
      sensitivity to local noise and modelling errors. By constraining tractography to
      ensure a connexion is found, and then inferring on the exact location of the
      connexion, we increase the robustness of connectivity-based parcellations,
      allowing parcellations of connexions that were previously invisible to
      tractography. The Bayesian framework allows a direct comparison of the evidence
      for connecting and non-connecting models, to test whether the connexion is
      supported by the data. Crucially, by explicit parameterisation of the connexion
      between brain regions, we infer on a parameter that is shared with models of
      functional connectivity. This model is a first step toward the joint inference on
      functional and anatomical connectivity.

PMID- 17543544
TI  - Topiramate in add-on therapy: results from an open-label, observational study.
AB  - An open-label, observational prospective study assessed the effectiveness of
      topiramate (TPM) as add-on therapy. A total of 450 patients aged 12 and above
      with a diagnosis of epilepsy and at least one epileptic seizure during the 12
      week retrospective baseline were to be documented. After baseline evaluation,
      topiramate was added. Ninety-five percent of patients had at least one baseline
      AED, most commonly Carbamazepine (53%) or Valproate (34%). In 5% TPM was started
      in monotherapy. Topiramate dose titration and target dose was determined by
      clinical response and side effect profile. Patients were intended to be followed
      for a total of 1 year which included 6 visits during which seizure frequency,
      adverse events, weight as well as clinical global impression were recorded.
      During the 12 weeks retrospective baseline, a median of 2.8 seizures per month
      were recorded which reduced significantly to 0.7 per month during the complete
      treatment phase (p < 0.0001). Seventy-two percent of patients had a > or =50%
      seizure reduction. Ten percent of patients were seizure free during the study.
      The most commonly reported adverse events were difficulties with memory (4.2%),
      somnolence (3.6%), and dizziness (2.7%). Overall, topiramate was well tolerated,
      and only 5% of patients discontinued treatment due to an adverse event. Retention
      in the study was higher than previously reported during randomized, dose
      controlled studies and is likely due to individualized doses as well as slower
      titration used.

PMID- 17543545
TI  - Public knowledge and attitudes towards epilepsy in Jordan.
AB  - BACKGROUND: Social acceptances of people with epilepsy very often constitute a
      considerable problem for patients and their family. Nationwide opinion polls on
      the public knowledge and attitudes towards epilepsy have been reported from
      several countries. The purpose of this study is to assess the knowledge and
      attitudes of the Jordanian public towards epilepsy, which have not been verified
      before. METHODS: A total of 16,044 people (8158 males and 7886 females) living in
      different areas of Jordan were interviewed by invitation using standard four set
      questionnaire constructed from previous similar studies (Caveness and Gallup)
      that tested public knowledge and attitudes toward epilepsy. Two hundred and
      thirty senior students of the faculty of pharmacy at Jordan University of Science
      and Technology are involved in this study. Each student interviewed at least 50
      individuals, aged 18 years or older, from their immediate community including
      family members, relatives, neighbors and friends by invitation. The interviews
      took place during the period from February to June of 2005. RESULTS: Eighty-eight
      percent had read or knew about epilepsy, and 52.4% had witnessed an epileptic
      attack at least once in their life. From the people interviewed, 84.7% believed
      that the cause of epilepsy is a neurological disease, and 80.6% believe that the
      main symptom is brief loss of consciousness. The response of the younger
      participants and those with higher education were statistically significant more
      positive regarding the knowledge on causes and symptoms of epilepsy. More than
      70% accepts shaking hands with people with epilepsy; they also believe that
      people with epilepsy are able to have children and to get high academic degrees.
      Less than 50% accepts letting their children play with children with epilepsy or
      employ people with epilepsy. Nine percent had negative attitudes, and believed
      that patients with epilepsy are insane and 88.5% objects the marriage of people
      with epilepsy to their sons or daughters. Approximately one third of the
      respondents believed that epilepsy is more dangerous than diabetes mellitus and
      hypertension. CONCLUSIONS: The overall knowledge and attitudes of Jordanians
      towards epilepsy is relatively comparable with the results from Asian countries
      but more negative when compared with reports from the Western countries.
      Consequently, well-organized educational campaigns are needed to improve public
      perception about epilepsy.

PMID- 17543546
TI  - Vagus nerve stimulation for medically refractory epilepsy: a long-term follow-up
      study.
AB  - INTRODUCTION: Vagus nerve stimulation (VNS) is thought to have a cumulative
      effect in time on seizure frequency reduction. There also might be other
      variables than reduction of seizure frequency in order to determine VNS efficacy.
      In this study we describe the long-term outcome of the first group of vagus nerve
      stimulation patients with pharmacoresistant epilepsy at the Medisch Spectrum
      Twente, The Netherlands. METHODS: This long-term descriptive prospective study
      included 19 patients, 11 males and 8 females, aged 17-46 years with
      pharmacoresistant epilepsy. They had received 3-16 (mean 9) different anti
      epileptic drugs and were not eligible for surgical resection of an epileptic
      focus. A vagus nerve stimulator was implanted in the period April 1999-October
      2001. Follow-up ranges from 2 to 6 years (mean 4 years). Efficacy was measured as
      the percentage change in seizure rate during 1 year and then after each year
      follow-up of VNS compared to 5 months baseline before implantation. RESULTS: Mean
      seizure reduction at 1-6 years was, respectively, 14% (n = 19), 25% (n =1 9), 29%
      (n = 16), 29% (n = 15), 43% (n = 9) and 50% (n = 7). Because of VNS two patients
      were able to start living without supervision. One patient died after 2 years of
      follow-up possibly as a result of SUDEP. Four patients had no apparent reduction
      in seizure frequency. Two of them had their stimulator removed. The other two
      patients however had significantly reduced post-ictal periods and seizure time
      and received a new pulse generator when the battery was depleted. One stimulator
      was switched off due to adverse effects, even though there was a positive effect
      on his seizure reduction. In six patients the medication regimen was changed
      during VNS by adding one anti-epileptic drug, however without significant change
      in seizure reduction. Adverse effects were hoarseness and coughing during
      stimulation. One patient had a temporary paralysis of his left vocal cord.
      CONCLUSION: We think that VNS is an effective treatment for pharmacoresistant
      epilepsy and its positive effect persists during the years of follow-up. Our
      results suggest that seizure reduction should not be considered as the only
      variable of importance to describe the outcome of VNS on epilepsy and it is
      worthwhile to look at other outcome measures.

PMID- 17543547
TI  - Exercise and injury increase chondroitin sulfate chain length and decrease
      hyaluronan chain length in synovial fluid.
AB  - OBJECTIVES: (1) To investigate the effects of exercise and osteochondral (OC)
      injury on synovial fluid (SF) chondroitin sulfate (CS) and hyaluronan (HA)
      concentration and chain length, (2) to compare SF and cartilage CS data from
      joints with OC fragmentation, and (3) to compare SF CS and HA profiles with those
      seen in serum from the same horses. METHODS: Serum and SF were obtained from (1)
      normal horses after 8 weeks rest, (2) the same horses after 9 months treadmill
      training, and (3) horses with OC injury from racing. Articular cartilage was also
      collected from group 3 horses. Concentrations and chain lengths of CS and HA were
      determined by gel chromatography and fluorophore-assisted carbohydrate
      electrophoresis. RESULTS: SF CS peak chain length in the OC injury group
      increased significantly (18.7kDa) when compared to rested horses (11.6kDa), with
      exercise producing an intermediate chain length (15.6kDa). Cartilage and serum
      from the OC injury group had the abnormally long CS chains seen in SF from these
      horses. Total SF HA was significantly lower in the OC injury group compared to
      the rested group. Both the OC injury group and the exercised group had
      significant decreases in SF HA chain length compared to the rested group.
      CONCLUSIONS: Chain length of SF CS was increased by exercise and OC injury.
      Exercise resulted in a modest increase, whereas OC injury caused a marked
      increase. In contrast to CS, SF HA chain length was decreased by OC injury, and
      to a lesser extent by exercise. Chain length analysis of SF CS and HA may provide
      a useful tool for evaluation of joint health.

PMID- 17543548
TI  - Electromyographic patterns suggest changes in motor unit physiology associated
      with early osteoarthritis of the knee.
AB  - OBJECTIVE: To assess characteristics of active motor units (MUs) during
      volitional vastus medialis (VM) activation in adults with symptomatic knee
      osteoarthritis (OA) across the spectrum of radiographic severity and age
      comparable healthy control volunteers. METHODS: We evaluated 39 participants (age
      65+/-3 years) in whom weight-bearing knee X-rays were assigned a Kellgren &
      Lawrence (KL) grade (18 with KL grade=0; four each with KL grades=1, 2 and 4;
      nine with grade 3). Electromyography (EMG) signals were simultaneously acquired
      using surface [surface EMG (S-EMG)] and intramuscular needle electrodes, and
      analyzed by decomposition-enhanced spike-triggered averaging to obtain estimates
      of size [surface-represented MU action potentials (S-MUAP) area], number [MU
      recruitment index (MURI)] and firing rates [MU firing rates (mFR)] of active MUs
      at 10%, 20%, 30% and 50% effort relative to maximum voluntary force [maximal
      voluntary isometric contraction (MVIC)] during isometric knee extension. RESULTS:
      Knee extensor MVIC was lower in OA participants, especially at higher KL grades
      (P=0.05). Taking the observed force differences into account, OA was also
      associated with activation of larger MUs (S-MUAP area/MVICx%effort; P<0.0001). In
      contrast, the estimated number of active units (MURI/MVICx%effort) changed
      differently as effort increased from 10% to 50% and was higher with advanced OA
      (KL=3, 4) than controls (P=0.0002). CONCLUSION: VM activation changes at the
      level of the MU with symptomatic knee OA, and this change is influenced by
      radiographic severity. Poor muscle quality may explain the pattern observed with
      higher KL grades, but alternative factors (e.g., nerve or joint injury, physical
      inactivity or muscle composition changes) should be examined in early OA.

PMID- 17543549
TI  - Glucosamine reduces anabolic as well as catabolic processes in bovine
      chondrocytes cultured in alginate.
AB  - OBJECTIVE: To investigate the working mechanism of glucosamine (GlcN) by studying
      the effect of different GlcN derivatives on bovine chondrocytes in alginate beads
      under anabolic and catabolic culture conditions. METHODS: Bovine chondrocytes
      seeded in alginate beads were treated with different concentrations of
      glucosamine-sulfate (GlcN-S), glucosamine-hydrochloride (GlcN-HCl) or N-acetyl
      glucosamine (GlcN-Ac). Culture conditions were anabolic, 3 day pre-culture
      followed by 14 days' treatment; catabolic, extracellular matrix (ECM) breakdown
      induced by 10ng/ml interleukin-1beta (IL-1beta); or a situation with balance
      between ECM breakdown and synthesis, 24 days' pre-culture followed by 14 days'
      treatment. The outcome measurements were total glycosaminoglycan (GAG) and DNA
      content per bead. RESULTS: In the situation with balance between ECM breakdown
      and synthesis, GlcN-Ac had a small stimulatory effect on total GAG content. GlcN
      S and GlcN-HCl had no effect. Under anabolic condition 5mM GlcN-S and GlcN-HCl
      significantly reduced total GAG content. GlcN-Ac did not show this effect. IL
      1beta induced catabolic effects were prevented by adding 5mM GlcN-HCl.
      Interference of GlcN with glucose (Gluc) was demonstrated by adding extra Gluc to
      the medium in the anabolic culture conditions. Increasing extracellular Gluc
      concentrations diminished the effect of GlcN. CONCLUSION: GlcN-S and GlcN-HCl,
      but not GlcN-Ac, reduce anabolic and catabolic processes. For anabolic processes
      this was demonstrated by decreased ECM synthesis, for catabolic processes by
      protection against IL-1beta mediated ECM breakdown. This might be due to
      interference of GlcN with Gluc utilization. We suggest that the claimed structure
      modifying effects of GlcN are more likely based on protection against ECM
      degradation than new ECM production.

PMID- 17543550
TI  - Genetic networks in nonpermissive temperature-induced cell differentiation of
      Sertoli TTE3 cells harboring temperature-sensitive SV40 large T-antigen.
AB  - To identify the molecular basis by which nonpermissive temperature (NPT) induces
      cell differentiation in Sertoli TTE3 cells harboring temperature-sensitive SV40
      large T-antigen, we performed global scale microarray and computational gene
      network analyses. In TTE3 cells, inactivation of the large T-antigen by a NPT at
      39 degrees C led to cell differentiation accompanying elevation of transferrin, a
      marker for differentiation of Sertoli cells, and CDKN1A, a cyclin-dependent
      kinase inhibitor. Of the 22,690 probe sets analyzed, NPT down-regulated 498 probe
      sets and up-regulated 432 probe sets by >2.0-fold. Hierarchical clustering
      analysis showed six gene clusters. In the down-regulated cluster I, a significant
      genetic network including fibronectin 1 was associated with cellular growth and
      proliferation. In up-regulated cluster IV, a significant genetic network
      including CDKN1A was associated with cellular differentiation. The present
      results provide additional novel insights into the molecular basis of cell
      differentiation induced by NPT in cells.

PMID- 17543551
TI  - Prevacuolar compartment morphology in vps mutants of Saccharomyces cerevisiae.
AB  - Over 60 genes have been identified that affect protein sorting to the lysosome
      like vacuole in Saccharomyces cerevisiae. Cells with mutations in these vacuolar
      protein sorting (vps) genes fall into seven general classes based upon their
      vacuolar morphology. Class A mutants have a morphologically wild type vacuole,
      while Class B mutants have a fragmented vacuole. There is no discernable vacuolar
      structure in Class C mutants. Class D mutants have a slightly enlarged vacuole,
      but Class E mutants have a normal looking vacuole with an enlarged prevacuolar
      compartment (PVC), which is analogous to the mammalian late endosome. Class F
      mutants have a wild type appearing vacuole as well as fragmented vacuolar
      structures. vps mutants have also been found with a tubulo-vesicular vacuole
      structure. vps mutant morphology is pertinent, as mutants of the same class may
      work together and/or have a block in the same general step in the vacuolar
      protein sorting pathway. We probed PVC morphology and location microscopically in
      live cells of several null vps mutants using a GFP fusion protein of Nhx1p, an
      Na(+)/H(+) exchanger normally localized to the PVC. We show that cell strains
      deleted for VPS proteins that have been previously shown to work together,
      regardless of VPS Class, have the same PVC morphology. Cell strains lacking VPS
      genes that have not been implicated in the same pathway show different PVC
      morphologies, even if the mutant strains are in the same VPS Class. These new
      studies indicate that PVC morphology is another tier of classification that may
      more accurately identify proteins that function together in vacuolar protein
      sorting than the original vps mutation classes.

PMID- 17543552
TI  - Notch signalling becomes transiently attenuated during long-term memory
      consolidation in adult Wistar rats.
AB  - Recent evidence has suggested a role for Notch in memory consolidation but the
      means by which this evolutionarily conserved mechanism serves these plasticity
      related processes remains to be established. We have examined a role for this
      signalling pathway in the hippocampal dentate gyrus of Wistar rats at increasing
      times following passive avoidance conditioning. Our principal finding is that a
      transient attenuation of Notch signalling occurs at the 10-12h post-training
      time. In this period, extracellular Notch-1 protein fragment exhibited a
      significant 2- to 3-fold increase but, by contrast, Notch-1 mRNA levels were
      significantly reduced. Moreover, transient inactivation of Notch-1 signalling was
      further suggested by concomitant reductions in the Notch ligand Jagged-1 and
      Notch-1 target protein Hes-1 mRNA levels. The C-terminal fragment of PS-1,
      necessary for gamma-secretase activity, was also significantly reduced at the 12h
      post-training time. These events were commensurate with the increase of a Notch
      immunoreactive fragment of 66 kDa in the nuclear fraction of the dentate gyrus.
      This fragment, identified with two different Notch-1 antisera, was not the
      expected NICD polypeptide of approximately 110 kDa and its accumulation was found
      to correlate with a significantly reduced expression of the Hes-1 transcriptional
      repressor. During the period of reduced Notch activity, a transient increase in
      soluble beta-catenin and GSK-3beta phosphorylation was observed, indicating a
      reciprocal activation of the Wnt signalling pathway. As down-regulation of Notch
      signalling promotes differentiation and neurite outgrowth in post-mitotic
      neurons, it is proposed that this pathway regulates the integration of synapses
      transiently produced during memory consolidation.

PMID- 17543553
TI  - Memory impairments and hippocampal modifications in adult rats with neonatal
      isolation stress experience.
AB  - Early life events have profound consequences. Our research demonstrates that the
      early life stress of neonatal isolation (1-h individual isolation on postnatal
      days 2-9) in rats has immediate and enduring neural and behavioral effects.
      Recently, we showed neonatal isolation impaired hippocampal-dependent context
      conditioned fear in adult rats. We now expand upon this finding to test whether
      neonatal isolation impairs performance in inhibitory avoidance and in the non
      aversive, hippocampal-dependent object recognition task. In addition to
      assessments of hippocampal-dependent memory, we examined if neonatal isolation
      results in cellular alterations in the adult hippocampus. This was measured with
      antibodies that selectively label calpain-mediated spectrin breakdown product
      (BDP), a marker of cytoskeletal modification that can have neuronal consequences.
      Neonatally isolated male and female rats showed impaired performance in both
      memory tasks as well as elevated BDP levels in hippocampal immunoblot samples. In
      tissue sections stained for BDP, the cytoskeletal fragmentation was localized to
      pyramidal neurons and their proximal dendrites. Interestingly, the hippocampal
      samples also exhibited reduced staining for the postsynaptic marker, GluR1.
      Neonatal isolation may render those neurons involved in memory encoding to be
      vulnerable to calpain deregulation and synaptic compromise as shown previously
      with brain injury. Together with our prior research showing enhanced striatal
      dependent learning and neurochemical responsivity, these results indicate that
      the early experience of neonatal isolation causes enduring yet opposing region
      specific neural and behavioral alterations.

PMID- 17543555
TI  - Peripheral vascular disease in an individual with pseudoxanthoma elasticum.

PMID- 17543554
TI  - Spleen tyrosine kinase Syk is necessary for E-selectin-induced alpha(L)beta(2)
      integrin-mediated rolling on intercellular adhesion molecule-1.
AB  - Engagement of neutrophils by E-selectin results in integrin activation. Here, we
      investigated primary mouse neutrophils in whole blood by using intravital
      microscopy and autoperfused flow chambers. Slow rolling on E-selectin
      coimmobilized with intercellular adhesion molecule-1 (ICAM-1) required P-selectin
      glycoprotein ligand (PSGL)-1, was dependent on alpha(L)beta(2) integrin (LFA-1),
      and required continuous E-selectin engagement. Slow rolling was abolished by
      pharmacological blockade of spleen tyrosine kinase (Syk) and was absent in Syk(-/
      ) bone-marrow chimeric mice. Treatment with tumor necrosis factor-alpha lowered
      rolling velocity further and induced CXC chemokine ligand-1 (CXCL1) and CXC
      chemokine receptor-2 (CXCR2)-dependent leukocyte arrest on E-selectin and ICAM-1.
      Arrest but not rolling was blocked by an allosteric inhibitor of LFA-1
      activation. Neutrophil recruitment in a thioglycollate-induced peritonitis model
      was almost completely inhibited in Selplg(-/-) mice or Syk(-/-) bone-marrow
      chimeras treated with pertussis toxin. This identifies a second neutrophil
      activation pathway that is as important as activation through G protein-coupled
      receptors (GPCRs).

PMID- 17543556
TI  - Renal vein thrombosis.
AB  - OBJECTIVE: The aim of this article is to review the published English literature
      on aetiology, pathology, clinical presentation, diagnostic methods and treatment
      of renal vein thrombosis. MATERIALS AND METHODS: We searched the published
      literature from Medline & Pubmed using keywords renal vein thrombosis, anti
      phospholipid syndrome and nephrotic syndrome. Data was extracted from individual
      case reports, case series, articles on pathology, diagnostic tests, treatment
      modalities, and previous reviews. Case reports which did not add any new
      information were excluded. RESULTS: We selected 60 references based on the above
      criteria. Renal vein thrombosis is relatively rare. CT angiography is considered
      the investigation of choice. Alternatives include MR angiography or renal
      venography in highly selected patients. As the condition is relatively uncommon,
      consensus on the best form of therapy for this condition has been slow to evolve.
      The trend in management has shifted to non-surgical therapies particularly
      systemic anticoagulation except in highly selected group of patients.

PMID- 17543557
TI  - Pony measurement: size really does matter.

PMID- 17543558
TI  - Insight into analysis of interactions of saquinavir with HIV-1 protease in
      comparison between the wild-type and G48V and G48V/L90M mutants based on QM and
      QM/MM calculations.
AB  - Saquinavir (SQV) was the first HIV-1 PR inhibitor licensed for clinical use and
      widely used for acquired immunodeficiency syndrome (AIDS) therapy. Its
      effectiveness, however, has been hindered by the emergence of resistant
      mutations. The two most important HIV-1 PR mutants are G48V and G48V/L90M.
      Inhibition studies of SQV on these mutants demonstrated 13.5- and 419-fold
      reductions of susceptibility, respectively. In this study, an analysis of
      energetic binding affinity between saquinavir and the HIV-1 PR wild-type and
      these two mutants has been performed in detail based on density functional theory
      and the hybrid quantum mechanical/molecular mechanical (QM/MM) calculations. We
      have found that the interaction of SQV with flap residue 48 of the mutants is
      significantly perturbed, as shown by the reduced stability of binding between SQV
      and residue 48 for the G48V and G48V/L90M mutants over the wild-type. This was
      associated with conformational changes of the inhibitor and the enzyme, leading
      to the loss of hydrogen bonding between the binding subsite P2 and the backbone
      carbonyl of residue 48. Moreover, the G48V/L90M mutations cause the repositioning
      of the residues close to residues 48 and 90, at important locations as a part of
      the flap and catalytic regions, respectively. The repositioning of these residues
      consequently perturbed the binding affinity of SQV in the pocket as indicated by
      the decreasing interaction energies. In addition to the loss of inhibitor/enzyme
      binding, it is interesting to observe that the mutation leads significantly to an
      increase of the stability of the enzyme.

PMID- 17543559
TI  - Bone properties in patients with acromegaly: quantitative ultrasound of the heel.
AB  - Growth hormone (GH) deficiency and acromegaly serve as good models for
      investigating the effects of GH on bone remodeling. However, the results from
      various studies are rather conflicting. The aim of our study was to estimate the
      potential role of gender, disease activity, and duration on both calcaneus
      quantitative ultrasound (QUS) parameters and bone turnover markers in patients
      with acromegaly. Thirty-six acromegalic patients (17 men, 19 women) and 3 age-
      and gender-adjusted controls for every patient were included in the study. The
      disease was active in 22 patients, and was considered cured in 14 of them. In
      each subject, QUS of the heel and parameters of bone turnover (bone alkaline
      phosphatase, beta-crosslaps, and osteocalcin) were measured. The results
      demonstrated lower QUS values in acromegalic patients compared with the controls.
      When stratified by gender, the differences in QUS parameters were significant in
      men, but not in women. Male patients with active disease had significantly lower
      QUS values than those in remission. Such differences were not observed among
      women. Multiple regression model indicated strong association between disease
      activity and the QUS parameters. The group of patients with active disease had a
      higher level of serum beta-crosslaps, whereas osteocalcin concentration was
      significantly increased only in male patients with active disease. The results of
      our study suggest significantly lower QUS values and increased bone turnover in
      male patients with active acromegaly. The disease activity is the strongest
      predictor of the QUS parameters in acromegalic patients.

PMID- 17543560
TI  - The correction of BMD measurements for bone strontium content.
AB  - Strontium ranelate (SR) is a new oral treatment for osteoporosis associated with
      large increases in bone mineral density (BMD) compared with alternative therapies
      such as bisphosphonates. Much of the BMD increase during SR treatment is a
      physical effect caused by the increased attenuation of X-rays due to the
      accumulation of strontium in bone tissue. The aim of this study was to assess the
      contribution made by bone strontium content (BSC) to the overall BMD increase by
      evaluating the percentage F of the BMD change explained by the physical presence
      of strontium in bone. A value of F less than 100% would provide evidence of the
      anabolic effect of SR as an additional factor contributing to the overall BMD
      increase. Studies of mixtures of strontium hydroxyapatite (SrHA) and calcium
      hydroxyapatite (CaHA) scanned on a variety of dual-energy X-ray absorptiometry
      (DXA) systems show that a 1% molar ratio of SrHA/(CaHA+SrHA) causes a 10%
      overestimation of BMD. The correction of spine BMD measurements for the physical
      effects of strontium depends on knowledge of 2 further factors: (1) bone biopsy
      measurements of iliac crest BSC and (2) the ratio R of BSC at the DXA site to BSC
      at the iliac crest measured in animal studies. We used clinical trial data and
      values of R(spine) measured in studies of monkeys and beagle dogs to determine
      values of F(spine) for 1, 2, and 3 yr treatment with SR. Based on the average
      value of R(spine) approximately 0.7 for male and female monkeys, we found values
      for F(spine) approximately 75-80% for 1, 2, and 3 yr of treatment. Using the
      value of R(spine) approximately 1.0 from the beagle study gave values of F(spine)
      approximately 100%. Although values of F(spine) as low as 40% are possible, we
      conclude that the most likely figure is 75% or greater. However, it is apparent
      that there are large uncertainties in the correction of BMD results for the
      effect of bone strontium and that the most important of these is the inference of
      BSC values at DXA scan sites from measurements of iliac crest bone biopsy
      specimens.

PMID- 17543561
TI  - Novel anti-inflammatory omega-3 PUFAs from the New Zealand green-lipped mussel,
      Perna canaliculus.
AB  - The present study has identified in the marine mollusc, Perna canaliculus, an
      homologous series of novel omega 3 polyunsaturated fatty acids (omega-3 PUFA)
      with significant anti-inflammatory (AI) activity. The free fatty acid (FFA) class
      was isolated from a supercritical-CO2 lipid extract of the tartaric acid
      stabilised freeze-dried mussel powder by normal phase chromatography, followed by
      reversed-phase high performance liquid chromatography (RP-HPLC). The RP-HPLC
      involved separation based on carbon numbers, followed by argentation-HPLC (Ag
      HPLC) of the methyl esters based on degree of unsaturation. Identification of the
      FFA components was performed using gas chromatography (GC) with flame ionisation
      detection, and individual structures were assigned by GC-mass spectroscopy (GC
      MS). Inhibition of leukotriene production by stimulated human neutrophils was
      used as an in vitro screening method to test the AI activity of the purified
      PUFAs. A structurally related family of omega-3 PUFAs was identified in the most
      bioactive fractions, which included C18:4, C19:4, C20:4, and C21:5 PUFA. The
      C20:4 was the predominant PUFA in the extract, and was a structural isomer of
      arachidonic acid (AA). The novel compounds may be biologically significant as AI
      agents, as a result of their in vitro inhibition of lipoxygenase products of the
      AA pathway.

PMID- 17543562
TI  - Binding of Bacillus thuringiensis Cry1A toxins to brush border membrane vesicles
      of midgut from Cry1Ac susceptible and resistant Plutella xylostella.
AB  - Plutella xylostella strain resistant (PXR) to Bacillus thuringiensis Cry1Ac toxin
      was not killed at even more than 1000 microg Cry1Ac/g diet but killed by Cry1Ab
      at 0.5 microg/g diet. In contrast, susceptible strain (PXS) was killed by Cry1Ac
      at 1 microg/g diet. Cy3-labeld Cry1A(s) binding to brush border membrane vesicles
      (BBMV) prepared from both strains were analyzed with direct binding assay. The Kd
      value of Cry1Aa to both BBMV was almost identical: 213.2 and 205.8 nM, and 263.5
      and 265.0 nM for Cry1Ac. The highest Kd values were in Cry1Ab which showed most
      effective insecticidal activity in PXS and PXR, 2126 and 2463 nM, respectively.
      These results clearly showed that the BBMV from PXR and PXS could equally bind to
      Cry1Ac. The binding between BBMV and Cy3-labeled Cry1Ac was inhibited only by
      anti-175 kDa cadherin-like protein (CadLP) and -252 kDa protein antisera, but not
      by anti-120 kDa aminopeptidase. This supports that resistance in PXR resulted
      from the abortion of pore formation after the binding of Cry1Ac to the BBMV. And
      furthermore, the importance of 175K CadLP and P252 proteins in those bindings was
      suggested. We briefly discuss possible mechanisms of the resistance.

PMID- 17543563
TI  - [Hormone replacement therapy in postmenopausal women: all the treatments are not
      the same. Do all the patients have the same characteristics?].

PMID- 17543564
TI  - [Specific follow-up for pregnant patients with a thyroid dysfunction].

PMID- 17543566
TI  - [Tissue resistance: what about tension-free?].

PMID- 17543567
TI  - [Newborn of HIV positive grandmother: reasons to be delighted or reasons to
      worry?].

PMID- 17543568
TI  - [Secondary breast cancer after treatment for Hodgkin's disease. About seven
      cases].
AB  - OBJECTIVE: Therapeutic results of Hodgkin disease (HD) have improved by the use
      of combined radio-chemotherapy. However, this association can increase the risk
      of on-term effects including secondary cancers. In a retrospective study, we
      collected secondary breast cancer (BC) in patients previously treated with
      chemoradiotherapy for Hodgkin disease at Salah-Azaiz institute of Tunis. PATIENTS
      AND METHODS: Between 1975 and 2003, seven patients (six women and one man)
      treated for HD subsequently developed BC. Mean age at diagnosis of HD was 21
      years (12-29). The first treatment was combined chemotherapy (MOPP-ABVD) and
      radiotherapy for all patients. Radiotherapy was delivered with cobalt 60 with
      large fields. The median dose was 41.3 Gy (2 Gy/fraction in 6 patients and 3.3 Gy
      in one). RESULTS: The breast tumours occurred after a median delay of 204 months
      (132-276). According to the TNM classification, we showed two stage T2, one stage
      T3, two stage T4b and two stage T4d. The mean clinical size was 47 mm (25-80 mm).
      All patients had infiltrating carcinoma. Axillary node histological involvement
      was found in 6 cases. All patients were treated by mastectomy and chemotherapy.
      Only one patient had a locoregional irradiation. Median survival was 26.5 months
      (12-48). Four patients died and three are still alive at respectively 24, 31 and
      144 months. DISCUSSION AND CONCLUSION: According to the previous data, breast
      cancer represents 6.3 to 9% of all second cancers occurring after HD treatment.
      We conclude that especially young women and girls treated for HD should be
      carefully monitored. We suggest that secondary BC be sometimes treated by
      conservative radiosurgical approach.

PMID- 17543569
TI  - Botulinum toxin improves the quality of life and reduces the intensification of
      depressive symptoms in patients with blepharospasm.
AB  - Blepharospasm (BSP) is a focal dystonia that results in hyperactivity of
      orbicular muscles of eyes. These symptoms often result in decreased quality of
      life (QoL) and symptoms of depression. Botulinum toxin type A is the current
      first line therapy. The aim of the present study was to analyze the impact of
      botulinum toxin treatment on the QoL and depressive symptoms in patients with
      BSP. The QoL was evaluated by means of the Short Form 36 questionnaire. The
      degree of the intensity of depression was evaluated by means of the Montgomery
      Asberg Depression Rating Scale. Botulinum toxin treatment significantly improves
      the QoL and reduces the intensity of depressive symptoms in all our study
      patients with BSP.

PMID- 17543570
TI  - Estimating the effects of light rail transit on health care costs.
AB  - In recent years, there has been a proliferation of research on the effects of the
      built environment, including mass transit systems, on health-related outcomes.
      While there is general agreement that the built environment affects travel
      choices and physical activity, it remains unclear how much of a public health
      benefit (in dollars) can be derived from land use policies that support walking,
      biking, and transit. In the present study, we develop a model to assess the
      potential cost savings in public health that will be realized from the investment
      in a new light rail transit system in Charlotte, NC. Relying on estimates of
      future riders, area obesity rates, and the effects of public transit on physical
      activity (daily walking to and from the transit stations), we simulated the
      potential yearly public health cost savings associated with this infrastructure
      investment. Our results indicate that investing in light rail is associated with
      a 9-year cumulative public health cost savings of dollars 12.6 million. While
      these results suggest that there is a sizable public health benefit associated
      with the adoption of light rail, they also indicate that the effects are
      relatively small compared to the costs associated with constructing and operating
      such systems. These findings suggest that planning efforts that focus solely on
      the health impact of modifications in the built environment are likely to
      overstate the economic benefits. Public health benefits should be considered
      along with broader environmental health benefits.

PMID- 17543571
TI  - ERK1/2 inactivation and p38 MAPK-dependent caspase activation during guanosine 5'
      triphosphate-mediated terminal erythroid differentiation of K562 cells.
AB  - Since differentiation therapy is one of the promising strategies for treatment of
      leukemia, universal efforts have been focused on finding new differentiating
      agents. In that respect, it was recently shown that guanosine 5'-triphosphate
      (GTP) induced the differentiation of K562 cells, suggesting its possible
      efficiency in treatment of chronic myelogenous leukemia (CML). However, further
      investigations are required to verify this possibility. Here, the effects of GTP
      on activation of mitogen-activated protein kinases (MAPKs) and caspases in K562
      cells were examined. Exposure of K562 cells to 100muM GTP markedly inhibited
      growth (4-70%) and increased percent glycophorin A positive cells after 1-6 days.
      GTP-induced terminal erythroid differentiation of K562 cells was accompanied with
      activation of three key caspases, i.e., caspase-3, -6 and -9. More detailed
      studies revealed that mitochondrial pathway is activated along with down
      regulation of Bcl-xL and releasing of cytochrome c into cytosol. Among MAPKs,
      ERK1/2and p38 were modulated after GTP treatment. Western blot analyses showed
      that sustained phosphorylation of p38 MAPK was accompanied by a decrease in
      ERK1/2 activation. These modulatory effects of GTP were observed at early
      exposure times before the onset of differentiation (3h), and followed for 24-96h.
      Interestingly, inhibition of p38 MAPK pathway by SB202190 impeded GTP-mediated
      caspases activation and differentiation in K562 cells, suggesting that p38 MAPK
      may act upstream of caspases in our system. These results point to a pivotal role
      for p38 MAPK pathway during GTP-mediated erythroid differentiation of K562 cells
      and will hopefully have important impact on pharmaceutical evaluation of GTP for
      CML treatment in differentiation therapy approaches.

PMID- 17543572
TI  - Molecular targeted therapies in breast cancer: where are we now?
AB  - Targeted therapies, in cancer treatment, represent a new generation of drugs that
      interfere with specific molecular targets (typically proteins) having critical
      roles to play in tumour growth or progression. The principle of targeted therapy
      is certainly not new: tamoxifen, a hormonal agent targeted at the estrogen
      receptor, has been in use for more than 30 years. However, this principle has re
      gained significant emphasis with the recent development of new biological agents,
      such as trastuzumab, which was first approved for the treatment of advanced
      breast cancer (BC) in 1998. Presently, there are at least three different
      targeted therapies with well documented activity in advanced BC and all three are
      now being studied in the adjuvant setting; trastuzumab and bevacizumab are
      monoclonal antibodies, and lapatinib is a dual inhibitor of HER-1 and HER-2. This
      paper will review the increasing role of molecular targeted therapies in BC, with
      a particular focus on those drugs currently being tested in early BC, as well as,
      on future perspectives.

PMID- 17543573
TI  - Early hematopoietic zinc finger protein-zinc finger protein 521: a candidate
      regulator of diverse immature cells.
AB  - The early hematopoietic zinc finger protein/zinc finger protein 521 (EHZF/ZNF521)
      is a recently identified, 1131 amino-acid-long nuclear factor that contains 30
      zinc fingers distributed in clusters throughout its sequence. A 13-AA motif, that
      binds to components of the nuclear remodelling and histone deacetylation (NuRD)
      complex and is conserved in several trascriptional co-repressors, is located at
      the amino-terminal end of the molecule. EHZF/ZNF521 expression is high in the
      most immature cells of the haematopoietic system and declines with
      differentiation. Its transcript is also abundant in brain, particularly in the
      cerebellum. Its murine counterpart, Evi3/Zfp521, is enriched in haematopoietic
      and neural stem cells, in cerebellar granule neuron precursors and in the
      developing striatum. Enforced expression of EHZF/ZNF521 in haematopoietic
      progenitors results in their expansion and in inhibition of differentiation.
      EHZF/ZNF521 is a member of the BMP signalling pathway and an inhibitor of the
      transcription factor OLF1/EBF1, implicated in the differentiation of neural
      progenitors and in the specification of the B-cell lineage. EHZF expression is
      observed in most acute myelogenous leukaemias and is particularly high in those
      with rearrangements of the MLL gene, where EHZF may contribute to the leukaemic
      phenotype. EHZF/ZNF521 is also abundant in medulloblastomas and other brain
      tumours. Taken together, the data available suggest a possible role for this
      factor in development, stem cell regulation and oncogenesis.

PMID- 17543574
TI  - The genotoxic and cytotoxic effects of nicotine in the mouse bone marrow.
AB  - The objective of the present study was to investigate the potential of nicotine
      to induce micronucleated polychromatic erythrocytes (MNPCE) in bone marrow of
      male and female mice. Cyclophosphamide at 40mg/kg was used as positive control
      clastogen. Single doses of 4, 8 or 16mg/kg nicotine were given via oral
      intubation and bone marrow was sampled at 18, 24, 30, 36 and 48h after treatment.
      Cyclophosphamide yielded the expected positive results. Despite the evident signs
      of acute toxicity shown by the animals, mainly at the 8 and 16mg/kg doses of
      nicotine, and the reduction in the % PCE, the results show that the MNPCE
      frequency in male and female mice was not affected by treatment with any of the
      selected doses of nicotine, in either of the sampling times 18 or 24h. However,
      at 30 and 36h after treatment, the MNPCE showed significant increases in both
      genders after doses of 8 and 16mg/kg. A sex-dependent response was recorded, with
      males having more MNPCE than females after treatment with 8 or 16mg/kg nicotine
      and sampling at 30h. However, at 36h more MNPCE were induced in females than in
      males, suggesting different degrees of dose interaction in the sexes under the
      conditions of the assay. The response was directly correlated with bone-marrow
      toxicity, as greater bone-marrow suppression was noted in females than in males
      when 36h samples were examined. By 48h recovery was observed even though the
      cytotoxicity was high. These findings suggest that nicotine at high doses and
      after prolonged time intervals is genotoxic and cytotoxic for mouse bone marrow.

PMID- 17543575
TI  - Genotoxicity of crotonaldehyde in the bone marrow and germ cells of laboratory
      mice.
AB  - Genotoxicity of crotonaldehyde was evaluated by employing bone marrow and
      spermatocyte chromosomal aberration and dominant lethal mutation assays in Swiss
      albino mice. For bone marrow chromosomal aberration assay, animals were treated
      with 0.2ml olive oil containing 8, 16 and 32microl kg b.w. of crotonaldehyde for
      6, 12 and 24h through single intraperitoneal injection. Treatment induced dose
      dependent and statistically significant decrease in mitotic index and increase in
      chromosome aberrations per cell (CAs/cell excluding gaps and stickiness and
      pulverizations) and percent aberrant metaphase (excluding gaps) in the bone
      marrow cells at 6, 12 and 24h after treatment. For spermatocyte chromosomal
      aberration assay, male mice were treated with 8, 16 and 32microl/kg b.w. of
      crotonaldehyde for 24h through single intraperitoneal injection. The percentage
      of the induced chromosome aberrations in diakinesis-metaphase-I cells showed dose
      dependent increase. For dominant lethal mutation assay, adult male mice were
      injected intraperitoneally with 0.2ml olive oil containing crotonaldehyde at the
      rate of 8, 16 and 32microl/kg b.w. for 5 consecutive days. The negative control
      animals received 0.2ml olive oil as above. In the dominant lethal mutation assay
      after the last dose, the treated males were allowed to mate with untreated virgin
      females. The mating continued for 5 consecutive weeks. At pregnancy days 14-16,
      the females were killed and uterine contents were examined for live and dead
      implants. Treatment of mice resulted in statistically significant decrease in the
      fertility indices and total number of implants per female. Statistically
      significant decrease in the number of live implants per female and increase in
      the number of dead implants per female were recorded in females mated with males
      during 8-14 and 15-21 and 22-28 days post-treatment mating. Crotonaldehyde
      treatment of males induced appreciably higher frequencies of dominant lethal
      mutation during 8-14, 15-21 and 22-28 days post-treatment mating periods. Percent
      dominant lethal mutation increased concomitantly with the dose. Dominant
      lethality was maximum in females mated with males treated with 5x32microl/kg b.w.
      during the 15-21 days post-treatment mating. The overall result suggests a
      positive dose-response relationship between treatment and induction of
      chromosomal aberrations in the somatic and germ cells and dominant lethal
      mutation in the germ cells.

PMID- 17543576
TI  - Evaluation of the new ARCHITECT Rubella IgM assay.
AB  - BACKGROUND: Rubella infections are usually characterized by mild self-limiting
      courses in immunocompetent individuals. However, infections in pregnant women
      during the first trimester of pregnancy pose a high risk of congenital rubella
      syndrome possibly resulting in severe defects in the unborn child. Rubella
      serology of a primary rubella infection is mainly determined by diagnostic
      confirmation of levels of specific IgM. STUDY DESIGN: Here, we report on the
      performance of the Rubella IgM assay in development on the ARCHITECT instrument,
      a fully automated high throughput chemiluminescent microparticle immunoassay
      platform. Sensitivity was examined using commercially available seroconversion
      panels from vaccinated individuals; specificity was addressed by testing
      populations of pregnant women, blood donors and hospitalized patients. In
      addition, the potential for assay interference was evaluated by testing samples
      of several disease states. As methods of comparison AxSYM, BioMerieux VIDAS and
      Behring Rubella IgM assays were used. RESULTS: The study demonstrates that the
      ARCHITECT Rubella IgM assay shows improved specificity compared to AxSYM and
      Behring. Seroconversion sensitivity is equivalent on all assays evaluated.
      CONCLUSION: Together with high throughput, optimized specificity and suppression
      of rheumatoid factor (RF) interference the ARCHITECT assay provides a useful
      improvement for the diagnosis of rubella serology.

PMID- 17543578
TI  - RdgB proteins: functions in lipid homeostasis and signal transduction.
AB  - The RdgBs are a group of evolutionarily conserved molecules that contain a
      phosphatidylinositol transfer protein (PITP) domain. However in contrast to
      classical PITPs (PITPalpha) with whom they share the conserved PITP domain, these
      proteins also contain several additional sequence elements whose functional
      significance remains unknown. The founding member of the family DrdgB alpha
      (Drosophila rdgB) appears to be essential for sensory transduction and
      maintenance of ultra structure in photoreceptors (retinal sensory neurons).
      Although proposed to support the maintenance of phosphatidylinositol 4, 5
      bisphosphate [PI (4, 5) P(2)] levels during G-protein coupled phospholipase C
      activity in these cells, the biochemical mechanism of DrdgB alpha function
      remains unresolved. More recently, a mammalian RdgB protein has been implicated
      in the maintenance of diacylglycerol (DAG) levels and secretory function at Golgi
      membranes. In this review we discuss existing work on the function of RdgB
      proteins and set out future challenges in understanding this group of lipid
      transfer proteins.

PMID- 17543579
TI  - Validation of the Augmentation Severity Rating Scale (ASRS): a multicentric,
      prospective study with levodopa on restless legs syndrome.
AB  - BACKGROUND: Augmentation is the main complication during long-term dopaminergic
      treatment of restless legs syndrome (RLS) and reflects an overall increase in RLS
      severity. Its severity varies considerably from a minor problem to a devastating
      exacerbation of disease. Despite its clinical relevance, systematic evaluations
      have rarely been undertaken and there has been no development of methods to
      assess the severity of augmentation. To fill this gap, the European RLS Study
      Group (EURLSSG) has developed the Augmentation Severity Rating Scale (ASRS),
      using three items that assess the degree of change in three specific dimensions
      of augmentation. The changes in each dimension are summed to give an ASRS total
      score. METHODS: The ASRS was developed to cover the basic dimensions defining RLS
      augmentation. The items were developed by an interactive process involving
      professional and patient input. The ASRS that was evaluated included four major
      items and two alternative forms of one item. The validation was conducted using
      63 (85%) mostly untreated RLS patients from six centers, who were treated for six
      months with levodopa (L-Dopa) (up to 500 mg/day, as clinically needed). Two
      consecutive assessments before and at baseline measured test-retest reliability.
      Consecutive ASRS ratings by two independent raters on a subsample of patients
      evaluated inter-rater reliability. Comparison with clinical severity ratings of
      two independent experts provided external validation of the ASRS. Comparison of
      patients with and without augmentation with regard to the items and the total
      score of the ASRS added discriminant validity. RESULTS: Sixty patients (63%
      females, mean age: 53 years, baseline International RLS Severity Rating (IRLS)
      score 24.7+/-5.2) were treated with a median daily dose of 300 mg L-Dopa (range:
      50-500 mg). Thirty-six patients (60%) experienced augmentation. Item analyses
      indicated that one item could be removed as it did not contribute significantly
      to the test score and only one form of the duplicated item needed to be used. The
      final ASRS then included three items. Test-retest reliability for the total score
      was rho=0.72, and inter-rater reliability was rcc=0.94. Cronbach's alpha was
      0.62. Validity as assessed by the correlation between the worst ASRS total score
      during the trial and the expert rating was rho=0.72. ASRS total score differed
      between patients without versus with augmentation (mean: 7.4 (standard deviation
      (SD)=4.0) vs. 2.0 (2.7) (P<0.0001). CONCLUSIONS: The ASRS is a reliable and valid
      scale to measure the severity of augmentation. Due to the need to systematically
      quantify augmentation for both long-term efficacy and tolerability, the ASRS may
      become a useful tool to monitor augmentation in future clinical trials.

PMID- 17543580
TI  - Research highlights from the PathoGenoMik Network 2001 - 2006.

PMID- 17543577
TI  - Sterol carrier protein-2: new roles in regulating lipid rafts and signaling.
AB  - Sterol carrier protein-2 (SCP-2) was independently discovered as a soluble
      protein that binds and transfers cholesterol as well as phospholipids
      (nonspecific lipid transfer protein, nsLTP) in vitro. Physiological functions of
      this protein are only now beginning to be resolved. The gene encoding SCP-2 also
      encodes sterol carrier protein-x (SCP-x) arising from an alternate transcription
      site. In vitro and in vivo SCP-x serves as a peroxisomal 3-ketoacyl-CoA thiolase
      in oxidation of branched-chain lipids (cholesterol to form bile acids; branched
      chain fatty acid for detoxification). While peroxisomal SCP-2 facilitates
      branched-chain lipid oxidation, the role(s) of extraperoxisomal (up to 50% of
      total) are less clear. Studies using transfected fibroblasts overexpressing SCP-2
      and hepatocytes from SCP-2/SCP-x gene-ablated mice reveal that SCP-2 selectively
      remodels the lipid composition, structure, and function of lipid rafts/caveolae.
      Studies of purified SCP-2 and in cells show that SCP-2 has high affinity for and
      selectively transfers many lipid species involved in intracellular signaling:
      fatty acids, fatty acyl CoAs, lysophosphatidic acid, phosphatidylinositols, and
      sphingolipids (sphingomyelin, ceramide, mono-di-and multi-hexosylceramides,
      gangliosides). SCP-2 selectively redistributes these signaling lipids between
      lipid rafts/caveolae and intracellular sites. These findings suggest SCP-2 serves
      not only in cholesterol and phospholipid transfer, but also in regulating
      multiple lipid signaling pathways in lipid raft/caveolae microdomains of the
      plasma membrane.

PMID- 17543581
TI  - Screening for haematological and iron-related abnormalities in elite athletes
      analysis of 576 cases.
AB  - The aim of this prospective, cohort study was to determine the clinical and
      performance related utility of haematological and iron-related screening in elite
      athletes. Three hundred and three male and 273 female elite athletes underwent
      routine medical screening over a three-year period. In association with a
      standard medical consultation, a full blood count and iron-related variables were
      measured. Ten male athletes had a serum ferritin less than 30ng/mL and satisfied
      AIS criteria for iron supplementation. In only one case was a disorder identified
      which was not expected following the clinical history and examination. Fifty-two
      female athletes had a serum ferritin less than 30ng/mL and satisfied AIS criteria
      for iron supplementation. In the females, there were no instances in which a
      medical condition was identified which was not expected following the clinical
      history and examination. In both groups, clinically non-significant abnormalities
      were generally minor or isolated reductions in haemoglobin and/or haematocrit,
      and alterations in red cell parameters or single measures of iron status.
      CONCLUSION: Screening for haematological and iron-related abnormalities in
      athletes has a low yield. Due to the critical nature of the effects of anaemia
      and low serum ferritin on some aspects of performance it is reasonable to perform
      a haemoglobin and a serum ferritin on male and female athletes entering an elite
      training program. Isolated abnormalities which are close to the limits of their
      normal ranges and not accompanied by symptoms or signs of illness can almost
      certainly be ignored.

PMID- 17543582
TI  - Predicting the 1000m rowing ergometer performance in 12-13-year-old rowers: the
      basis for selection process?
AB  - Performance-predictive parameters have been established for rowers representing
      different quality levels, sexes, weight categories and classifications, but none
      have been designed for very young rowers (age <14). The objective of this study
      was to predict 1000-m rowing ergometer performance based on 12 anthropometric and
      six physiological variables in 48 male rowers (age range 12.0-13.9 year; mean+/
      S.D. 12.94+/-0.61) and to determine the key parameters that would perhaps provide
      a scientific basis for talent identification and the selection process in rowing.
      The subjects completed an incremental maximal treadmill test. Their body height
      (r=-0.79), body mass (r=-0.60), lean body mass (r=-0.82), leg length (r=-0.72),
      arm length (r=-0.71), bicristal diameter (r=-0.63), biacromial diameter (r=
      0.73), upper arm girth (r=-0.34), forearm girth (r=-0.63), thigh girth (r=-0.29),
      calf girth (r=-0.54), maximal oxygen uptake (in L/min, r=-0.89; and in mL/kg/min,
      r=-0.36), maximal ventilation (r=-0.77), and oxygen uptake at ventilatory
      anaerobic threshold (r=-0.87) correlated with 1000-m time (p<0.05), while percent
      body fat, percent of maximal oxygen uptake at ventilatory anaerobic threshold and
      maximal lactate did not. Performance correlated significantly with age (r=-0.46;
      p<0.01), so it was important to consider this effect in the resulting regression
      models. Multiple regression procedures indicated that the model comprising
      anthropometric and physiological variables combined best predicts performance
      (R(2)=0.85), followed by models that comprised physiological (R(2)=0.80) and
      anthropometric (R(2)=0.76) variables alone. In conclusion, in rowers aged 12-13
      year a higher aerobic capacity (as measured by maximal oxygen uptake in L/min),
      and a larger body size are beneficial for performance over 1000-m rowing
      ergometer distance.

PMID- 17543583
TI  - Effects of a 30-min running performed daily after downhill running on recovery of
      muscle function and running economy.
AB  - This study investigated the effects of a 30-min level running performed daily for
      6 days after downhill running (DHR) on indicators of muscle damage and running
      economy (RE). Fifty men were placed into five groups - control (CON), 40%, 50%,
      60% and 70% (10 subjects per group) - by matching the baseline maximal oxygen
      consumption (V O(2max)) among the groups. Subjects in the 40%, 50%, 60% and 70%
      groups had a treadmill (0 degrees ) run for 30min at 40%, 50%, 60% and 70% of the
      pre-determined V O(2max), respectively, at 1-6 days after a bout of 30-min DHR at
      -15% (-8.5 degrees ). Maximal voluntary isometric strength of the knee extensors,
      muscle soreness, plasma creatine kinase and lactate dehydrogenase activities were
      measured before, immediately after and every day for 7 days after DHR. RE was
      assessed by oxygen consumption, minute ventilation, respiratory exchange ratio,
      lactate, heart rate and rating of perceived exertion during a 5-min level running
      at 85% V O(2max) performed before and at 2, 5 and 7 days after DHR. All muscle
      damage markers changed significantly (P<0.05) after DHR without significant
      differences among the groups. The RE parameters showed a significant decrease in
      RE for 7 days after DHR, but no significant differences in the changes were
      evident among the groups. These results suggest that the daily running performed
      after DHR did not have any beneficial or adverse effects on recovery of muscle
      damage and RE regardless of the intensity.

PMID- 17543584
TI  - TAME: development of a new method for summarising adverse events of cancer
      treatment by the Radiation Therapy Oncology Group.
AB  - BACKGROUND: We aimed to examine deficiencies in established methods of
      summarising adverse events, and to create a new reporting system (TAME) for
      summarising the toxicity burden of cancer treatment. TAME consolidates
      traditional adverse-event data into three risk domains: short-term (acute)
      Toxicity (T), Adverse long-term (late) effects (A), and Mortality risk (M)
      generated by a treatment programme (E=End results); and assigns treatments to
      risk classes for each risk domain. METHODS: We examined formally an established
      method for summarising adverse events (the max-grade method) in five trials of
      patients with head and neck cancer done between September, 1991, and August,
      2000, by the Radiation Therapy Oncology Group (RTOG) that involved 13 treatment
      groups (2304 patients). We calculated TAME summary metrics that included time and
      multiplicity factors in the same patient groups. We compared relative T values
      with relative values for toxic effects from the max-grade approach. We also
      calculated the range of individual patient T scores in two groups from one of the
      trials (the laryngeal-preservation trial). RESULTS: The max-grade method
      systematically excluded 29-70% of total reported high-grade (grade 3-4) acute
      adverse events, contained progressive bias, and favoured higher toxicity
      programmes. Relative T values in the 13 treatment programmes tested showed an
      increase of almost 500% in acute toxicity burden (100-590) between treatment
      groups compared with a 170% increase (100-270) between treatment groups by use of
      the max-grade method. The difference between these two summary systems was
      statistically significant (mean difference -102 [95% CI -167 to -37], p=0.005, t
      test for paired differences). Four risk classes were designated for acute and
      relative late effects: low (100-140), moderate (150-390), high (400-490), and
      extreme (>or=500). The distribution of individual patient T scores showed that 82
      (60%) patients who received concurrent platinum-radiotherapy for larynx
      preservation reported two or more high-grade events, and 34 (20%) reported four
      or more high-grade events; these findings differed significantly from the
      distribution of individual patient T scores for patients who received
      radiotherapy alone, in which 32 (19%) reported two or more high-grade events and
      3 (3%) reported four or more high-grade events (p<0.0001). The max-grade method
      also systematically excluded 26-48% of high-grade (grade 3-4) late adverse
      events. However, less variation was noted in the relative risk of late events
      (100-270) by the TAME method for late effects. INTERPRETATION: Traditional
      methods for summarising adverse events systematically exclude important data,
      giving an inaccurate impression of the toxicity burden in complex multimodality
      trials. By contrast, T values use data on all high-grade adverse events. T values
      are proportional to the intensity of treatment, showing a 500% increase between
      treatment groups in acute toxicity burden in RTOG trials of head and neck cancer
      done during this study interval. TAME reporting provides a concise and uniform
      method to compare relative risk among treatment options. Future studies should
      include testing the performance of the TAME system in additional datasets (from
      different research organisations and disease sites), prospective correlation of
      TAME endpoints with predefined outcome measures, and assessment of its usefulness
      in clinical decision making.

PMID- 17543585
TI  - Second-generation endometrial ablation technologies: the hot liquid balloons.
AB  - Hysteroscopic endometrial ablation (HEA) was introduced in the 1980s to treat
      menorrhagia. Its use required additional training, surgical expertise and
      specialized equipment to minimize emergent complications such as uterine
      perforations, thermal injuries and excessive fluid absorption. To overcome these
      difficulties and concerns, thermal balloon endometrial ablation (TBEA) was
      introduced in the 1990s. Four hot liquid balloons have been introduced into
      clinical practice. All systems consist of a catheter (4-10mm diameter), a
      silicone balloon and a control unit. Liquids used to inflate the balloons include
      internally heated dextrose in water (ThermaChoice, 87 degrees C), and externally
      heated glycine (Cavaterm, 78 degrees C), saline (Menotreat, 85 degrees ) and
      glycerine (Thermablate, 173 degrees C). All balloons require pressurization from
      160 to 240 mmHg for treatment cycles of 2 to 10 minutes. Prior to TBEA,
      preoperative endometrial thinning, including suction curettage, is optional.
      Several RCTs and cohort studies indicate that the advantages of TBEA include
      portability, ease of use and short learning curve. In addition, small diameter
      catheters requiring minimal cervical dilatation (5-7 mm) and short duration of
      treatment cycles (2-8 min) allow treatment under minimal analgesia/anesthesia
      requirements in a clinic setting. Following TBEA serious adverse events,
      including thermal injuries to viscera have been experienced. To minimize such
      injuries some surgeons advocate the use of routine post-dilatation hysteroscopy
      and/or ultrasonography to confirm correct intrauterine placement of the balloon
      prior to initiating the treatment cycle. After 10 years of clinical practice,
      TBEA is thought to be the preferred first-line surgical treatment of menorrhagia
      in appropriately selected candidates. Economic modeling also suggested that TBEA
      may be more cost-effective than HEA.

PMID- 17543586
TI  - Chronic pain in multiple sclerosis: prevalence, characteristics, and impact on
      quality of life in an Australian community cohort.
AB  - This cross-sectional study describes chronic pain in 94 persons with multiple
      sclerosis residing in the community. The characteristics of chronic pain, pain
      related disability, pain treatments, barriers to health care, and impact on
      quality of life were examined. Sixty-four percent of participants reported
      chronic pain; of these, 60% had dysesthetic pain and 70% had episodic increases
      in pain. The mean numerical pain intensity rating score was moderate (5). Chronic
      Pain Grade was used to classify severity of pain, using scores for items for pain
      intensity and pain-related disability. Those in the higher pain grades had more
      disability and recorded more health care visits (P = .06) (not significant
      because of small sample size). Effective pain management techniques included
      analgesic medication and physical measures as reported by 54% and 44%
      participants, respectively. Participants' perceived barriers to health care
      included environmental and personal factors. Those with multiple sclerosis and
      pain, compared with those with no pain, showed a significant difference in the
      domain of psychological well-being scores (P = .01) on the Assessment of Quality
      of Life scale. Additionally, the domains of independent living (P = .009) and
      total scores (P = .04) showed better quality of life in participants with lower
      pain grades. Improved understanding of chronic pain in this population may
      facilitate early identification for timely intervention and minimize pain-related
      disability. PERSPECTIVE: This article describes chronic pain in persons with
      multiple sclerosis living in the community. The information regarding pain
      prevalence, pain-related disability, and impact on quality of life provides
      insight into the complex multidimensional pain experience. Improved understanding
      of pain and early intervention may contribute to the overall well-being and
      decrease pain-related disability in this population.

PMID- 17543587
TI  - Caffeic acid phenethyl ester (CAPE) protects rat skeletal muscle against ischemia
      reperfusion-induced oxidative stress.
AB  - Oxygen-derived free radicals have been implicated in the pathogenesis of skeletal
      muscle injury after ischemia-reperfusion. Caffeic acid phenethyl ester, an active
      component of propolis extract, exhibits antioxidant properties. The aim of this
      study was to assess the effects of caffeic acid phenethyl ester (CAPE) and alpha
      tocopherol (vit E) on ischemia/reperfusion (I/R) injury in a rat hind limb
      ischemia/reperfusion model. For this purpose, ischemia was induced in
      anesthetized rats by unilateral (right) femoral artery clipping for 2 h followed
      by 2 h of reperfusion. Four groups were studied: sham, I/R, I/R+CAPE and I/R+vit
      E. Drugs were administered intraperitoneally after 1 h of ischemia and I/R rats
      received saline vehicle. After 2 h of reperfusion, venous blood was sampled and
      the right gastrocnemius muscle was harvested. Plasma and tissue were assayed for
      malondialdehyde (MDA), superoxide dismutase (SOD) and nitric oxide (NO)
      metabolites. Tissue was also assayed for catalase (CAT) activity. Both tissue and
      plasma NO levels, MDA levels, SOD activities was significantly increased in I/R
      groups compared to control groups. The two treated groups showed decreased MDA
      and NO in both muscle and plasma compared to the I/R group. No differences were
      noted in muscle tissue SOD in three I/R groups, but SOD activity were increased
      in the plasma of I/R+CAPE and I/R+vit E groups compared with I/R group. Whereas
      tissue CAT activity was not changed among groups. Our results indicate that CAPE
      has antioxidant properties similar to those of vit E in this model and may
      attenuate the harmful effects of hind limb I/R in skeletal muscle.

PMID- 17543588
TI  - Chemosensitivity of unmyelinated axons in isolated human gastric vagus nerve.
AB  - Vagal afferent neurons from the stomach may be activated not only by chemical
      stimuli in the mucosa but also by circulating factors. In the present study, we
      have used electrophysiological techniques to characterize functional activity of
      several receptors for chemical mediators on unmyelinated axons in isolated
      fascicles of human gastric vagus nerve. Application of agonists at the nicotinic
      acetylcholine receptor (nAChR), 5-HT(3) subtype of serotonin receptor, and the
      transient receptor potential vanilloid receptor-1 (TRPV1) resulted in a change in
      the height and/or threshold of the C-fiber compound action potential. These
      effects were blocked by specific antagonists of nAChR (mecamylamine), 5-HT(3) (Y
      25130), and TRPV1 (capsazepine). We conclude that the chemosensitivity of
      unmyelinated vagal axons can be studied using isolated segments of human gastric
      vagus nerve. The presence of receptors indicates that circulating factors may
      modify vagal afferent neurons also by effects on the axonal membrane.

PMID- 17543589
TI  - Scale structure of heart-rate dynamics: multifractality or artefacts?

PMID- 17543590
TI  - Evolutionary dynamics and spatial genetic structure of epizootic hemorrhagic
      disease virus in the eastern United States.
AB  - Epizootic hemorrhagic disease virus (EHDV) is a significant pathogen of wild and
      domestic ungulates worldwide. In North America, serotype EHDV-2 is responsible
      for the majority of outbreaks, which are most commonly observed in white-tailed
      deer. A recent study by Murphy et al. [Murphy, M.D., Howerth, E.W., MacLachlan,
      N.J., Stallknecht, D.E., 2005. Genetic variation among epizootic hemorrhagic
      disease viruses in the southeastern United States: 1978-2001. Infect. Genet.
      Evol. 5, 157-165] examined the genetic relationships of EHDV-2 sequences from
      outbreaks across the eastern United States for evidence of temporal and spatial
      structure but found no evidence for either. Here, I present results of further
      examination of the same data using additional types of analysis. Contrary to the
      earlier assessment, I find that for outbreaks observed within the same year,
      genetic and spatial distances are in fact positively correlated and that the
      virus is evolving at a rate similar to that seen in other vector-born RNA
      viruses. Estimates of demographic history further revealed that population sizes
      of the virus had remained relatively stable over most of its history. A
      noticeable exception to this trend was a recent demographic bottleneck, possibly
      associated with a selective sweep, that affected one of the two viral genes
      examined. These results demonstrate that genetic variation accumulating at
      selectively neutral and measurably evolving sites in the EHDV-2 genome can be
      employed to gain insights into the spatial and temporal dynamics of this viral
      pathogen.

PMID- 17543591
TI  - Ventilatory control and acid-base regulation across the menstrual cycle in oral
      contraceptive users.
AB  - We examined the effect of menstrual cycle (MC) phase on acid-base regulation and
      ventilatory control at rest in monophasic oral contraceptive (OC) users. Twelve
      healthy women (25+/-1 years; mean+/-S.E.) were tested during the inactive (IP;
      5.1+/-0.2 days) and active (AP; 21.1+/-0.7 days) pill phase of the MC. Central
      and peripheral chemoreflex responsiveness was examined using a modified CO(2)
      rebreathing procedure. Minute ventilation (V E), breathing pattern and metabolic
      rate were measured during 10 min of quiet, resting breathing. Blood for the
      determination of arterial P(CO2) (Pa(CO2)) and hydrogen ion concentration
      ([H(+)]); plasma concentrations of the strong ion difference ([SID]) and total
      weak acid ([A(tot)]); serum concentrations of progesterone ([P(4)]) and 17beta
      estradiol ([E(2)]) were also obtained. Although [E(2)] (p<0.05) and [A(tot)]
      (p=0.05) were increased in the IP versus AP, MC phase had no significant effect
      on resting V E, breathing pattern, metabolic rate, [H(+)], Pa(CO2), [SID], [P(4)]
      and central or peripheral chemoreflex characteristics. Overall, OC had no
      significant physiological effect on acid-base regulation or ventilatory control
      at rest in healthy women. This may reflect suppression of endogenous fluctuations
      in circulating [P(4)] typically observed across the MC in healthy, eumenorrheic
      non-OC users.

PMID- 17543592
TI  - HPLC method for the determination of carboplatin and paclitaxel with cremophorEL
      in an amphiphilic polymer matrix.
AB  - Simple and rapid reversed phase HPLC methods for individual as well as
      simultaneous analysis of paclitaxel and carboplatin with cremophorEL (CrEL) in an
      amphiphilic polymer matrix were developed. Different analytical performance
      parameters such as linearity, accuracy, precision, specificity, limit of
      detection (LOD) and limit of quantification (LOQ) were determined according to
      ICH guidelines. All the analytical methods were developed by reverse phase HPLC
      on C-18 column with a mobile phase comprising of water-acetonitrile run on
      isocratic mode for the analysis of carboplatin and gradient mode for individual
      analysis of paclitaxel and for simultaneous analysis of the two drugs at a flow
      rate of 1 ml/min at 227 nm. The proposed methods for independent analysis of the
      drugs elute out carboplatin in 4.3 min and paclitaxel in 10.5 min while in
      simultaneous analysis carboplatin shows R(t) at 4 min and paclitaxel at 18 min
      with a continuous run for 17 more minutes to elute out CrEL. These methods were
      found to be specific as none of the components of the media, i.e. polymer, CrEL
      and buffer interfered with the drug peaks. The linearity of the calibration
      curves for each analyte in the desired concentration range was found to be good
      (r(2)>0.9995). The methods were accurate and precise with recoveries ranging from
      98 to 101% for each drug and relative standard deviation (%RSD) <2%. Peaks
      corresponding to each of the drug showed positive value for the minimum peak
      purity index over the entire range of integrated chromatographic peak thus
      indicating the purity of the peaks. Stability analysis of the two drugs revealed
      that the drugs remain stable during the period of study.

PMID- 17543593
TI  - Fast molecular diagnostics of canine T-cell lymphoma by PCR and capillary gel
      electrophoresis with laser-induced fluorescence detector.
AB  - Lymphoma is the most common hematopoietic tumor in dogs and manifests as a
      proliferation of malignant lymphoid cells primarily affecting the lymph nodes or
      solid visceral organs. We describe the use of capillary gel electrophoresis (CGE)
      with a laser-induced fluorescence (LIF) detector based on polymerase chain
      reaction (PCR) to rapidly detect a disorder of the canine T-cell receptor gamma
      (TCRgamma) gene. After the PCR amplification of the specific TCR( gene in dogs,
      the 90-bp DNA fragment amplified was separated in a fused-silica capillary by CGE
      LIF. Under an electric field of 375 V/cm and with a sieving matrix of 1.5% poly
      (ethyleneoxide) (M(r) 600,000), the amplified PCR products were analyzed within 4
      min by CGE separation. When the CGE-LIF method was applied to real clinical
      samples of the specific DNA fragment of the TCR( gene, the migration time and the
      corrected peak area showed relative standard deviations (n=5) of 0.29% and 0.58%,
      respectively. Both methods of CGE-LIF and slab gel electrophoresis showed same
      results for nine clinical samples. This PCR/CGE-LIF technique may prove to be a
      new fast and simple tool for the rapid diagnosis of the PCR-amplified DNA of
      canine T-cell lymphoma.

PMID- 17543594
TI  - Novel loci regulating bone anabolic response to loading: expression QTL analysis
      in C57BL/6JXC3H/HeJ mice cross.
AB  - Variations in the expression levels of bone marker genes among the inbred strains
      of mice in response to mechanical loading (ML) are largely determined by genetic
      factors. To explore this, we performed four-point bending on tibiae of 10-week
      female F2 mice of B6XC3H cross using 9N at 2 Hz, 36 cycles, once per day for 12
      days. We collected tibiae from these mice for RNA extraction. We then measured
      the expression changes of bone marker genes, bone sialoprotein (BSP), alkaline
      phosphatase (ALP) and housekeeping genes, beta-actin and peptidylprolyl isomerase
      A (PPIA), by using real-time PCR in both the loaded and the non-loaded tibiae of
      F2 mice (n=241). A genome-wide scan was performed using 111 micro satellite
      markers in DNA sample collected from these mice. Mean increase in gene
      expression, expressed as fold change, ranges from 2.8 to 3.0 for BSP and 2.7 to
      2.8 for ALP. Both showed a skewed distribution with a heritability response of 87
      to 91%. Absence of significant correlation between the increased gene expression
      vs. body weight (BW) and bone size (BS) suggests that bone response to loading is
      independent of BS or BW. Non-parametric mapping (MapQTL program 5) revealed that
      BSP and ALP expression in response to bending was regulated by several
      significant and suggestive QTL: Loci regulating both BSP and ALP were located on
      Chr 8 (60.1 cM), 16 (45.9 cM), 17 (14.2 cM), 18 (38.0 cM) and Chr 19 (3.3 cM);
      Loci specific to BSP were found on Chrs 1 (LOD score 10.4 at 91.8 cM), 5 (5.2 at
      73.2 cM) and 9 (7.0 at 13.1 cM); Loci regulating only ALP were found on Chrs 1
      (7.6 at 46 and 75.4 cM), 3 (8.3 at 47 cM) and 4 (5.6 at 54.6 cM). QTLs on Chrs 1,
      3, 8, 9, 17 and 18 correspond to QTLs we previously reported by pQCT
      measurements, thus validating these findings. In addition, we found that the QTL
      associated with non-loaded tibiae for BSP and ALP on Chrs 4, 16 and 18 was
      identical to the QTLs associated with ML. This finding suggests that regions on
      these chromosomes are responsible for natural variation in expression of BSP and
      ALP as well as for ML. This is the first expression study to provide evidence for
      the presence of multiple genetic loci regulating bone anabolic response to
      loading in the B6XC3H intercross and will lead to a better understanding of how
      exercise improves the skeletal mass.

PMID- 17543595
TI  - Blockade of beta-adrenergic signaling does not influence the bone mechano
      adaptive response in mice.
AB  - The involvement of the sympathetic nervous system (SNS) in the modulation of bone
      adaptation to its load-bearing demand remains controversial. This study tested
      the involvement of SNS in the adaptive response of trabecular and cortical bone
      to either external loading or disuse. External loading consisted of cyclic strain
      (40 cycles, peak 1500 microstrain) applied for 7 min, 3 days/week, while disuse
      was induced by unilateral sciatic neurectomy (SN). C57Bl/J6 mice, female, 9 weeks
      old, were subjected to loading or disuse for 2 weeks. Half of the loaded and SN
      mice were injected with the beta-adrenergic antagonist, propranolol (PRO, 20
      mug/g) 1 week before the start of loading or disuse and during all the duration
      of the experiment. MicroCT analysis of the tibiae showed that the applied load
      induced significant changes on both trabecular architecture and cortical geometry
      compared to the contralateral controls, indicating increased bone mass. In
      contrast, disuse markedly reduced trabecular and cortical indexes. However, these
      adaptive responses were not altered by PRO treatment. We further tested whether
      the lack of protective effect of PRO against disuse-induced bone loss was due to
      the very short duration of treatment by blocking SNS signaling for 8 weeks with
      either PRO (0.5 mg/ml in drinking water) or guanethidine sulfate (GS, 40 mug/g,
      injected). At the end of fourth week of treatment, mice underwent SN surgery so
      that disuse was induced for the remaining 4 weeks. Again, neither PRO nor GS
      treatments altered the disuse-induced bone loss in the neurectomized tibia. In
      addition, blockade of SNS signaling for either 3 or 8 weeks did not affect the
      basal trabecular bone architecture in control tibiae and in L4 vertebrae. This
      study shows that the mechano-adaptive response occurring in trabecular and
      cortical bone upon loading or disuse is not altered by inactivation of beta
      adrenergic signaling. Furthermore, sympathectomy had no effect on trabecular bone
      at different skeletal sites. This suggests that the osteo-regulatory action of
      beta-adrenergic signaling is not involved in the bone mechano-adaptive response
      and must therefore affect other bone regulatory pathways.

PMID- 17543599
TI  - Novel analytical procedures for screening of drug residues in water, waste water,
      sediment and sludge.
AB  - Traces of pharmaceuticals are continuously introduced into the aquatic
      environment mainly by sewage treatment plant effluents. Final data about their
      impact on the ecosystem are still partly missing. Progress in instrumental
      analytical chemistry has resulted in the availability of methods that allow a
      monitoring of these pollutants at ng L(-1) levels. In this review the state-of
      the-art of residue analysis of pharmaceuticals by chromatographic and
      electrophoretic techniques is summarized. Improvements in detection limits over
      the past years have mainly been due to sophisticated mass spectrometric detection
      techniques. Furthermore, robust sample preparation and preconcentration protocols
      based on solid-phase extraction and related procedures have contributed
      significantly to the achievements observed so far. This review also covers
      several immunochemical approaches which may serve as an inexpensive alternative
      for quick screening of samples.

PMID- 17543600
TI  - Modelling of retention of pesticides in reversed-phase high-performance liquid
      chromatography: quantitative structure-retention relationships based on solute
      quantum-chemical descriptors and experimental (solvatochromic and spin-probe)
      mobile phase descriptors.
AB  - A quantitative structure-retention relationship (QSRR) analysis based on
      multilinear regression (MLR) and artificial neural networks (ANNs) is carried out
      to model the combined effect of solute structure and eluent composition on the
      retention behaviour of pesticides in isocratic reversed-phase high-performance
      liquid chromatography (RP-HPLC). The octanol-water partition coefficient and four
      quantum chemical descriptors (the total dipole moment, the mean polarizability,
      the anisotropy of the polarizability and a descriptor of hydrogen-bonding based
      on the atomic charges on acidic and basic chemical functionalities) are
      considered as solute descriptors. In order to identify suitable mobile phase
      descriptors, encoding composition-dependent properties of both methanol- and
      acetonitrile-containing mobile phases, the Kamlet-Taft solvatochromic parameters
      (polarity-dipolarity, hydrogen-bond acidity and hydrogen-bond basicity, pi*,
      alpha and beta, respectively) and the 14N hyperfine-splitting constant (aN) of a
      spin-probe dissolved in the eluent are examined. A satisfactory description of
      mobile phase properties influencing the solute retention is provided by aN and
      beta or alternatively pi* and beta. The two seven-parameter models resulting from
      combination of aN and beta, or pi* and beta, with the solute descriptors were
      tested on a set of 26 pesticides representative of 10 different chemical classes
      in a wide range of mobile phase composition (30-60% (v/v) water-methanol and 30
      70% (v/v) water-acetonitrile). Within the explored experimental range, the
      acidity of the eluent, as quantified by alpha, is almost constant, and this
      parameter is in fact irrelevant. The results reveal that aN and pi*, that can be
      considered as interchangeable mobile phase descriptors, are the most influent
      variables in the respective models. The predictive ability of the proposed
      models, as tested on an external data set, is quite good (Q2 close to 0.94) when
      a MLR approach is used, but the modelling capability can be further improved
      using an artificial neural network.

PMID- 17543601
TI  - Determination of sulfonamides in milk after precolumn derivatisation by micellar
      liquid chromatography.
AB  - A simple method to identify and determine six sulfonamides (sodium sulfacetamide,
      sulfamethizole, sulfaguanidine, sulfamerazine, sulfathiazole and
      sulfamethoxazole) in milk by micellar liquid chromatography (MLC) is reported.
      The assay makes use of a precolumn diazotisation-coupling derivatisation
      including the formation of an azo dye that can be detected at 490 nm.
      Furthermore, the use of MLC as an analytical tool allows the direct injection of
      non-purified samples. The separation was performed with an 80 mM SDS-8.5%
      propanol eluent at pH 7. Analysis times are below 16 min with a complete
      resolution. Linearities (r>0.9999), as well as intra- and inter-day precision
      (below 2.7%), were studied in the validation of the method. The limits of
      detection and quantification ranged from approximately 0.72 to 0.94 and 2.4 to
      3.1 ng mL(-1), respectively. The detection limit was below the maximum residue
      limit established by the European Community. Finally, recoveries in spiked milk
      samples were in the 83-103% range.

PMID- 17543604
TI  - Simultaneous estimation of zeta potential and slip coefficient in hydrophobic
      microchannels.
AB  - Electroosmotic flows through hydrophobic microchannels experience velocity slip
      at the channel wall, which increases the volumetric flow rate at a given electric
      potential gradient. The conventional method of zeta potential estimation using
      the volumetric flow rate may yield quite inaccurate zeta potential unless the
      velocity slip is appropriately taken care of. In the present investigation we
      develop a method for simultaneous estimation of zeta potential and velocity slip
      coefficient in the electroosmotic flow through a hydrophobic microchannel using
      velocity measurements. The relevant inverse problem is solved through the
      minimization of a performance function utilizing a conjugate gradient method. The
      present method is found to estimate the zeta potential and slip coefficient
      accurately even with noisy velocity measurements.

PMID- 17543603
TI  - Molecularly imprinted solid phase extraction for the selective HPLC determination
      of alpha-tocopherol in bay leaves.
AB  - A new sorbent for molecularly imprinted solid phase extraction (MISPE) was
      synthesized to extract and purify alpha-tocopherol (alpha-TP) from vegetable
      sources. Molecularly imprinted polymers (MIP) were synthesized using methacrylic
      acid (MAA) as functional monomer and ethylene glycol dimethacrylate (EGDMA) as
      crosslinking agent using a photo-polymerization procedure. A thermo
      polymerization was also performed but no imprinting effect in the resulting
      materials was raised. The proposed MISPE protocol could overcome the drawback of
      traditional detection methods, which require pre-treatments of the samples. The
      possibility to obtain the selective recognition of alpha-TP from natural samples
      in aqueous mixtures represents one of the main advantages of our materials. Our
      procedure involves the direct HPLC injection of eluate without any treatment and
      above all the use of no toxic and biocompatible organic solvents. After the
      evaluation of the selectivity of the alpha-TP imprinted polymers, the performance
      of these materials as solid phase extraction (SPE) sorbents was investigated. Our
      MISPE-HPLC procedure has a high sensitivity, LOD and LOQ were 3.49x10(-7) and
      1.16x10(-6) mol L(-1), respectively, as well as good precision (intraday
      precision below 3.3% and interday precisions below 6.5%) and recovery (60%).
      Thus, it can be successfully used for the purification of alpha-TP from bay
      leaves.

PMID- 17543605
TI  - Selective and sensitive hydroxypropyl-beta-cyclodextrin based sensor for simple
      monitoring of (+)-catechin in some commercial drinks and biological fluids.
AB  - (+)-Catechin (CAT) was considered as a polyphenolic compound abundantly contained
      in plants. It exerts protective effect against cancer, inflammatory and
      cardiovascular diseases. These protective effects are mainly attributed to its
      antioxidative activity by scavenging free radicals. Therefore, the need of
      simple, selective and sensitive monitoring of (+)-catechin in commercial drinks
      and biological fluids is crucial. A new selective and sensitive voltammetric
      quantification of (+)-catechin was investigated at low cost hydroxypropyl-beta
      cyclodextrin modified carbon paste sensor in acidic solutions. The constructed
      sensor was treated in simple and fast manner to increase its stability for
      catechin determination. The effect of solution and instrumental parameters was
      investigated by using osteryoung square-wave anodic voltammetry (OSWAV) at pH
      2.20 and differential pulse cathodic voltammetry (DPCV) at pH 4.40 in 0.10 M
      Britton-Robinson buffer. Acidic solutions were chosen to increase the stability
      of (+)-catechin, reduce its adsorption on the sensor surface and increase the
      selectivity of proposed method. Cyclic voltammetry (CV) was used to elucidate the
      electrochemical mechanism of catechin at the modified electrochemical sensor. A
      linear range up to 7.20 and 4.20 microg mL(-1) of catechin was achieved in anodic
      and cathodic voltammetry, respectively. The method gave reproducible and reliable
      results with 1.50 g mL(-1) catechin (S.D. 0.062). Limit of detection of 0.12 and
      0.30 ng mL(-1) and limit of quantification (LOQ) of 1.10 and 2.80 ng mL(-1) were
      easily achieved using anodic and cathodic voltammetry, respectively. Selectivity
      of the proposed procedure was estimated by testing recovery and adding the most
      interfering metal ions and/or organic compounds. The proposed method was applied
      successfully to selective determination of catechin in some commercial drinks
      like tea, cocoa and coffee with acceptable recovery range (98-102%). The
      extraction of catechin was rather simple, making it suitable for studies with a
      large number of commercial samples. Furthermore, the application to urine samples
      without pretreatment was achieved and statistically confirmed at 95% confidence
      level. It was easy to analyze catechin in urine down to 0.55 ng mL(-1).

PMID- 17543606
TI  - Different experimental results for the influence of immersion angle on the
      resonant frequency of a quartz crystal microbalance in a liquid phase: with a
      comment.
AB  - This paper presents different experimental results of the influence of an
      immersion angle (theta, the angle between the surface of a quartz crystal
      resonator and the horizon) on the resonant frequency of a quartz crystal
      microbalance (QCM) sensor exposed one side of its sensing surfaces to liquid. The
      experimental results show that the immersion angle is an added factor that may
      influence the frequency of the QCM sensor. This type of influence is caused by
      variation of the reflection conditions of the longitudinal wave between the QCM
      sensor and the walls of the detection cell. The frequency shifts, measured by
      varying theta, are related to the QCM sensor used. When a QCM sensor with a weak
      longitudinal wave is used, its resonant frequency is nearly independent of theta.
      But, if a QCM sensor with a strong longitudinal wave is employed, the immersion
      angle is a potential error source for the measurements performed on the QCM
      sensor. When the reflection conditions of the longitudinal wave are reduced, the
      influence of theta on the resonant frequency of the QCM sensor is negligible. The
      slope of the plot of frequency shifts (deltaF) versus (rho eta)(1/2), the square
      root of the product of solution density (rho) and viscosity (eta), may be
      influenced by theta in a single experiment for the QCM sensor with a strong
      longitudinal wave in low viscous liquids, which can however, be effectively
      weakened by using the averaged values of reduplicated experiments. In solutions
      with a large (rho eta)(1/2) region (0-55 wt% sucrose solution as an example, with
      rho value from 1.00 to 1.26 g cm(-3) and eta value from 0.01 to 0.22 g cm(-1) s(
      1), respectively), the slope of the plot of deltaF versus (rho eta)(1/2) is
      independent of theta even for the QCM sensor with a strong longitudinal wave in a
      single experiment. The influence of theta on the resonant frequency of the QCM
      sensor should be taken into consideration in its applications in liquid phase.

PMID- 17543607
TI  - Immersion angle dependence of the resonant-frequency shift of the quartz crystal
      microbalance in a liquid: effects of longitudinal wave.
AB  - We investigated the effects of the longitudinal wave on the immersion angle
      dependence of the resonant-frequency shift, deltaF, of the quartz crystal
      microbalance, QCM. In order to study exactly the effects, we employed the three
      types of cells: normal cell, cell with the glass beads and cell with sponge. The
      longitudinal wave exists in the normal cell. On the other hand, both the cell
      with the glass beads and the cell with sponge eliminate the longitudinal wave. As
      results, we have found that the tendencies of deltaF are the same in the three
      types of cells. That is, we conclude that the longitudinal wave does not have
      effects on the immersion angle dependence of deltaF.

PMID- 17543608
TI  - Computer-assisted prediction of pesticide substructure using mass spectra.
AB  - Mass spectral classifiers of 16 substructures that are present in basic
      structures of pesticides have been investigated to assist pesticide residues
      analysis as well as screening of pesticide lead compounds. Mass spectral data are
      first transformed into 396 features, and then Genetic Algorithm-Partial Least
      Squares (GA-PLS) as a feature selection method and Support Vector Machine (SVM)
      as a validation method are implemented together to get an optimization feature
      set for each substructure. At last, a statistical method which is AdaBoost
      algorithm combined with Classification and Regression Tree (AdaBoost-CART) is
      trained to predict the 16 substructures presence/absence using the optimization
      mass spectral feature set. It is demonstrated that the optimum feature sets can
      be used to predict the 16 pesticide substructures presence/absence with mostly 85
      100% in recognition success rate instead of the original 396 features.

PMID- 17543610
TI  - Determination of the dose-depth distribution of proton beam using resazurin assay
      in vitro and diode laser-induced fluorescence detection.
AB  - In this study the dose-depth distribution pattern of proton beams was
      investigated by inactivation of human cells exposed to high-LET (linear energy
      transfer) protons. The proton beams accelerated up to 45 MeV were horizontally
      extracted from the cyclotron, and were delivered to the cells acutely through a
      home made prototype over a range of physical depths (in the form of a variable
      water column). The biological systems used here were two in vitro cell lines,
      including human embryonic kidney cells (HEK 293), and human breast adenocarcinoma
      cell line (MCF-7). Cells were exposed to unmodulated proton beam radiation at a
      dose of 50 Gy similar to that used in therapy. Resazurin metabolism assay was
      investigated for measurement of cell response to irradiation as a simple and non
      destructive assay. In the resazurin reduction test the non-fluorescent probe dye
      is reduced to pink and highly fluorescent resorufin. The dose-depth distribution
      of proton beam obtained based on the highly sensitive laser-induced fluorometric
      determination of resorufin was found to coincide well with the data collected
      using conventional film based dosimetry. The resazurin method yielded data
      comparable with the optical micrographs of the irradiated cells, showing the
      least cell survival at the measured Bragg-peak position of 10 mm. In addition,
      fused silica capillary was used as a sample container to increase the probability
      for irradiated laser beam to probe and excite resorufin in small sample volume of
      the capillary. The developed method has the potential to serve as a non
      destructive, sample-thrifty, and time saving tool to realize more realistic,
      practical dose-depth distribution of proton beam compared to conventional in
      vitro cell viability assessment techniques.

PMID- 17543609
TI  - Matrix assisted laser desorption ionization-time of flight mass spectrometry
      analysis of hyaluronan oligosaccharides.
AB  - A new method is presented for the identification of oligosaccharides obtained by
      enzymatic digestion of hyaluronan (HA) with bacterial hyaluronidase (E.C.
      4.2.2.1, from Streptomyces hyalurolyticus) using matrix assisted laser desorption
      ionization-time of flight mass spectrometry (MALDI-TOFMS). Mixtures containing HA
      oligosaccharides of tetrasaccharide (4-mer)-34-mer were analyzed using this
      method. The carboxyl groups of the glucuronate residues in the prepared HA
      oligomers, were modified as the acidic form (-COOH), sodium salts (-COONa),
      organic ammonium salts, or methylesters before MALDI-TOFMS measurement. Among
      these samples, the methylester form of glucuronate residues in HA
      oligosaccharides, prepared by methylation using trimethylsilyl diazomethane,
      afforded high sensitivity for spectra. This simple modification method for
      carboxyl group methylation of acidic polysaccharides [Hirano et al., Carbohydr.
      Res., 340, (2005) 2297-2304] provides samples suitable for MALDI-TOF mass
      spectrometric analysis throughout a significantly enhanced range of masses.

PMID- 17543611
TI  - Prediction of the retention in thin layer chromatography screening systems by
      atomic contributions.
AB  - A novel atomic-contribution system for predicting of R(M) values is presented and
      validated on 13 thin layer chromatography screening systems on silica gel, where
      the large experimental datasets (198-761 R(M) values) are available. The R(M) is
      predicted with error less than 0.5 in majority of solutes (besides several
      outliers), which corresponds to difference in R(F) equal to 0.28 in the worst
      case. The system was validated by dividing the data into training and validation
      datasets, proving its accuracy. The main reason of larger errors in outliers are:
      large conjugated heterocycles, quarternary ammonium cations, large amount of
      polar atoms or very simple but unique molecules. The calculations are very easy
      and can be performed on free software or even manually. The presented method can
      be used in the retention prediction of new solutes in existing chromatographic
      screening systems.

PMID- 17543613
TI  - Are foxes guarding your henhouse?

PMID- 17543619
TI  - Note to self: tips on internal & external communication.

PMID- 17543620
TI  - Leader of the "free" world: the challenges of managing a volunteer system.

PMID- 17543621
TI  - Forget something? Create a breakaway connection for your shoreline.

PMID- 17543622
TI  - Pediatric T-tubes: unfamiliar technology requires caretaker assistance.

PMID- 17543623
TI  - Nitro line with CPAP: a new standard of care.

PMID- 17543624
TI  - Get smart: how educated are EMS instructors?

PMID- 17543626
TI  - Ambulance safety first: experts convene to discuss personal & patient safety
      issues.
AB  - Six national experts formed an Ambulance Safety Roundtable at the 25th Annual EMS
      Today Conference & Exposition in March 2007 in Baltimore to discuss safety
      concerns, from current poor ambulance design to methods for improving driving
      skills. The event--sponsored by Wheeled Coach and moderated by Rick Patrick, MS,
      EMT-P, a safety expert and deputy fire chief for the Estero (Fla.) Fire Rescue
      District--highlighted issues regarding personal and patient safety. Patrick led
      the discussion by noting that available data indicates an increase in the number
      of ambulance crashes each year. In addition to the personal toll these collisions
      inflict, more and more ambulance operators are being held accountable for
      incidents they cause. Charges of negligent homicide and costly lawsuits are
      becoming more common. As a result, the care and safety of prehospital providers
      while traveling to and from calls has become a critical issue for many emergency
      service providers.

PMID- 17543628
TI  - Airway fundamentals: integrating technology into basic airway management.

PMID- 17543629
TI  - Paramedic or EMT-basic partner? Study evaluates preferred partner types & the
      effect of partners on work-related stress levels.

PMID- 17543632
TI  - Coffee, tea or medical.

PMID- 17543630
TI  - Down to the (growing) bone: understanding & detecting pediatric orthopedic
      trauma.

PMID- 17543633
TI  - Perioperative management of patients with coronary stents.
AB  - Perioperative coronary stent thrombosis is a catastrophic complication that can
      occur in patients receiving both bare-metal and drug-eluting stents. Noncardiac
      surgery appears to increase the risk that recently-placed stents thrombose,
      especially when surgery is performed early after stenting, and particularly if
      dual antiplatelet therapy is discontinued. We reviewed the existing data about
      the frequency of stent thrombosis after noncardiac surgery and explored the
      impact of delay from surgery and discontinuation of antiplatelet therapy. We also
      reviewed the data about the impact of preoperative revascularization in patients
      known to require noncardiac surgery. Based on these published data, we offer
      recommendations that can be used to guide the treatment of patients who require
      noncardiac surgery after having received a stent.

PMID- 17543634
TI  - Multicenter, randomized, double-blind, placebo-controlled study on the effect of
      oral tolvaptan on left ventricular dilation and function in patients with heart
      failure and systolic dysfunction.
AB  - OBJECTIVES: This study sought to examine the effects of vasopressin V2 receptor
      antagonism with tolvaptan on the changes in left ventricular (LV) volumes over
      time. BACKGROUND: Vasopressin levels may be increased in patients with heart
      failure (HF) and may be a factor driving the progression of HF. METHODS: This was
      a multicenter, randomized, double-blind, placebo-controlled trial conducted to
      evaluate the effect of long-term administration of the vasopressin V2-receptor
      antagonist tolvaptan (30 mg/day) on reducing left ventricular end-diastolic
      volume (LVEDV) compared with placebo in patients with HF and reduced systolic
      function, using quantitative radionuclide ventriculography at baseline, repeated
      after 1 year of therapy, and repeated again approximately 1 week after withdrawal
      of study drug. RESULTS: A total of 120 patients were randomized to tolvaptan and
      120 were randomized to placebo. In the placebo group, there was no change in
      LVEDV over the course of follow-up (change of 0.0 +/- 10.0 ml/m2). After 1 year
      of tolvaptan, there was a small reduction in LV volume (decrease of 1.8 +/- 10.7
      ml/m2); the between-group difference was not significant (p = 0.21). During the
      course of the trial, there were 6 deaths (5%) and 21 HF hospitalizations (18%) in
      the tolvaptan group, compared with 11 deaths (9%) and 34 HF hospitalizations
      (28%) in the placebo group. In a time-to-event analysis, there was a significant
      favorable effect of tolvaptan on the composite of mortality or heart failure
      hospitalization (p < 0.03 by log-rank test). CONCLUSIONS: In a well-treated
      population of stable HF patients, there was no significant effect of tolvaptan
      therapy on LV volumes observed during 1 year of therapy. Nonprespecified natural
      history data favored therapy with tolvaptan, with a reduction in the combined end
      point of mortality and heart failure hospitalization observed. (Multicenter,
      Randomized, Double-Blind, Placebo Controlled, Efficacy Study on the Effects of
      Tolvaptan on Left Ventricular Dilatation in Congestive Heart Failure Patients;
      http://clinicaltrials.gov/ct/show/NCT00043758?order=1; NCT00043758).

PMID- 17543635
TI  - Arginine vasopressin receptor antagonists for heart failure: a winter climbing to
      the Everest's tip?

PMID- 17543636
TI  - Elevated plasma fibrinogen level predicts suboptimal response to therapy with
      both single- and double-bolus eptifibatide during percutaneous coronary
      intervention.
AB  - OBJECTIVES: This study sought to determine the factors associated with suboptimal
      platelet inhibition (PI) with single- and double-bolus eptifibatide during
      percutaneous coronary intervention (PCI). BACKGROUND: Although PI > or = 95%
      measured 10 min after glycoprotein IIb/IIIa inhibitor therapy is associated with
      improved outcomes following PCI, this level of PI often is not achieved. METHODS:
      We prospectively studied 150 patients undergoing PCI with single-bolus
      eptifibatide (180 microg/kg) (n = 100) and double-bolus eptifibatide (180
      microg/kg administered 10 min apart) (n = 50) followed by standard infusion (2
      microg/kg/min). Measuring platelet aggregation at baseline and at 10 min and 30
      to 45 min after eptifibatide bolus, patients were classified as optimal
      responders (OPT) (> or =95% PI) or suboptimal responders (sub-OPT) (<95% PI)
      based on 10-min PI after final bolus. RESULTS: Suboptimal PI was achieved in 61%
      of patients with single-bolus eptifibatide and in 36% with double-bolus
      eptifibatide. In the single-bolus group, sub-OPT had higher fibrinogen levels
      (324 +/- 85 mg/dl vs. 259 +/- 49 mg/dl, p = 0.0002), platelet counts (221 +/- 70
      vs. 186 +/- 47, p = 0.008), and white blood cell counts (7.7 +/- 2.3 vs. 6.6 +/-
      1.9, p = 0.02). In the double-bolus group, sub-OPT also had higher fibrinogen
      levels (324 +/- 68 mg/dl vs. 278 +/- 53 mg/dl, p = 0.01) and were more likely to
      be smokers (38.9% vs. 9.4%, p = 0.01). Multivariable analysis showed that
      fibrinogen level was the only independent predictor of suboptimal PI, with
      fibrinogen cutoffs at 375 and 325 mg/dl predicting suboptimal PI (single-bolus:
      100% and 90.0%, respectively; double-bolus: 100% and 60%, respectively) with both
      doses. CONCLUSIONS: During PCI, both single- and double-bolus eptifibatide
      provide suboptimal PI in a substantial proportion of patients. A fibrinogen level
      >375 mg/dl is a strong predictor of suboptimal PI.

PMID- 17543637
TI  - Glomerular filtration rate and N-terminal pro-brain natriuretic peptide as
      predictors of cardiovascular mortality in vascular patients.
AB  - OBJECTIVES: The purpose of this work was to assess the prognostic role of
      glomerular filtration rate (GFR) and NT-terminal pro-B-type natriuretic peptide
      (NT-proBNP) for mortality end points in the vascular population. BACKGROUND: The
      GFR and NT-proBNP have been shown to predict mortality end points in free-living
      and limited vascular populations, independent of traditional risk factors.
      However, their prognostic power in an unrestricted vascular population is poorly
      understood. METHODS: A total of 412 subjects from a vascular cohort with a
      history of either peripheral arterial disease (PAD) and/or other cardiovascular
      disease (CVD) were included in this prospective cohort analysis and followed for
      an average of 6.7 years. Outcome variables were all-cause mortality, ischemic
      heart disease (IHD) mortality, and any cardiovascular mortality. The prognostic
      roles of GFR and NT-proBNP levels were determined using multivariate survival
      analysis. RESULTS: Higher GFR (per 10 ml/min/1.73 m2) was significantly
      protective for all-cause mortality (hazard ratio [HR] 0.81, p < 0.001), IHD
      mortality (HR 0.82, p = 0.008), and CVD mortality (HR 0.84, p = 0.005).
      Conversely, NT-proBNP was not a significant predictor of any mortality end point.
      The GFR showed the strongest association in subjects with a history of other CVD.
      Although NT-proBNP did not demonstrate a significant prognostic role in any of
      the subgroups, the data were suggestive for patients with PAD alone. CONCLUSIONS:
      Glomerular filtration rate was a robust predictor of all-cause, IHD, and
      cardiovascular mortality in the vascular population, particularly in those with a
      history of other CVD, while NT-proBNP showed a suggestive association limited to
      the group with PAD only. These findings suggest that these markers must be
      selectively applied in the vascular population for greatest clinical utility.

PMID- 17543638
TI  - Homocysteine modulates the CD40/CD40L system.
AB  - OBJECTIVES: This study evaluated the impact of hyperhomocysteinemia (HHcy) on the
      CD40/CD40 ligand (CD40L) dyad in vivo and in vitro. BACKGROUND:
      Hyperhomocysteinemia is associated with an increased incidence of
      atherothrombosis, although the molecular mechanisms of this association are
      incompletely defined. The CD40L pair triggers inflammatory signals in cells of
      the vascular wall, representing a major pathogenetic pathway of atherosclerosis.
      METHODS: We used a commercially available enzyme-linked immunosorbent assay kit
      to evaluate circulating levels of soluble (s) CD40L in 24 patients with HHcy and
      24 healthy subjects. We also used real-time polymerase chain reaction and flow
      cytometry to determine expression levels of CD40 and vascular cell adhesion
      molecule (VCAM)-1 in human umbilical vein endothelial cells (HUVECs) and of CD40L
      in human platelets. RESULTS: The sCD40L levels were significantly increased in
      HHcy patients (median [interquartile range] 8.0 [0.7 to 10.5] ng/ml vs. 2.1 [1.9
      to 2.3] ng/ml, p = 0.0001). Positive correlations were noted between log sCD40L
      and log homocysteine (Hcy) (R = 0.68, p < 0.0001) or log sVCAM-1 (R = 0.41, p <
      0.005). Homocysteine significantly stimulated CD40 mRNA expression in HUVECs (p =
      0.033). Consistently, 24-h exposure to Hcy increased the percentage of CD40
      expressing cells (p = 0.00025). Homocysteine also significantly enhanced CD40L
      expression in platelets (p = 0.025) to a comparable extent as that of thrombin.
      Notably, Hcy increased VCAM-1 protein expression induced by CD40L in HUVECs (p =
      0.0046). CONCLUSIONS: The present results uncover a potential molecular target of
      Hcy, namely the CD40/CD40L dyad. Collectively, they indicate that upregulation of
      CD40/CD40L signaling may represent a link between HHcy and an increased risk of
      cardiovascular disease.

PMID- 17543639
TI  - Impact of mitral valve annuloplasty combined with revascularization in patients
      with functional ischemic mitral regurgitation.
AB  - OBJECTIVES: The aim of this work was to determine whether mitral valve (MV)
      annuloplasty benefits patients with moderate/severe (3+/4+) functional ischemic
      mitral regurgitation (MR) who undergo coronary artery bypass grafting (CABG).
      BACKGROUND: Mitral regurgitation is a strong predictor of poor outcomes in
      patients with ischemic cardiomyopathy; whether correcting it at the time of CABG
      improves outcomes is less certain. METHODS: From 1991 to 2003, 390 patients with
      3+/4+ ischemic MR had CABG with (n = 290) or without (n = 100) MV annuloplasty.
      Groups were propensity-matched using demographics, extent of coronary disease,
      regional wall motion, and quantitative electrocardiography. Survival,
      echocardiographic severity of MR, and New York Heart Association (NYHA)
      functional class were compared. RESULTS: One-, 5-, and 10-year survival was 88%,
      75%, and 47% after CABG alone and 92%, 74%, and 39% after CABG + MV annuloplasty
      (p = 0.6). Mortality was increased in patients with severe lateral wall motion
      abnormalities (p = 0.05), ST-segment elevation in lateral leads (p < 0.004), and
      higher QRS voltage sum (p < 0.0001). Patients undergoing CABG alone were more
      likely to have 3+/4+ postoperative MR than those undergoing CABG + MV
      annuloplasty (48% vs. 12% at 1 year, p < 0.0001). The NYHA functional class
      substantially improved in both groups (p < 0.001) and remained improved; at 5
      years, 23% of patients having CABG + mitral annuloplasty and 25% having CABG
      alone were in NYHA functional class III/IV. CONCLUSIONS: Although CABG + MV
      annuloplasty reduces postoperative MR and improves early symptoms compared with
      CABG alone, it does not improve long-term functional status or survival in
      patients with severe functional ischemic MR. The MV annuloplasty in this setting,
      without addressing fundamental ventricular pathology, is insufficient to improve
      long-term clinical outcomes.

PMID- 17543640
TI  - Adding mitral valve annuloplasty to surgical revascularization does not benefit
      patients with functional ischemic mitral regurgitation.

PMID- 17543641
TI  - Usefulness of 64-slice multislice computed tomography coronary angiography to
      assess in-stent restenosis.
AB  - OBJECTIVES: This study sought to evaluate the diagnostic accuracy of 64-slice
      multislice computed tomography (MSCT) coronary angiography in the follow-up of
      patients with previous coronary stent implantation. BACKGROUND: Recent
      investigations have shown increased image quality and diagnostic accuracy for
      noninvasive coronary angiography with 64-slice MSCT as compared with previous
      generation MSCT scanners, but data on the evaluation of coronary stents are
      scarce. METHODS: In 182 patients (152 [84%] male, ages 58 +/- 11 years) with
      previous stent (> or =2.5 mm diameter) implantation (n = 192), 64-slice MSCT
      angiography using either a Sensation 64 (Siemens, Forchheim, Germany) or Aquilion
      64 (Toshiba, Otawara, Japan) was performed. At each center, coronary stents were
      evaluated by 2 experienced observers and evaluated for the presence of
      significant (> or =50%) in-stent restenosis. Quantitative coronary angiography
      served as the standard of reference. RESULTS: A total of 14 (7.3%) stented
      segments were excluded because of poor image quality. In the interpretable
      stents, 20 of the 178 (11.2%) evaluated stents were significantly diseased, of
      which 19 were correctly detected by 64-slice MSCT. Accordingly, sensitivity,
      specificity, and positive and negative predictive value to identify in-stent
      restenosis in interpretable stents were 95.0% (95% confidence interval [CI] 85%
      to 100%), 93.0% (95% CI 90% to 97%), 63.3% (95% CI 46% to 81%), and 99.3% (95% CI
      98% to 100%), respectively. CONCLUSIONS: In-stent restenosis can be evaluated
      with 64-slice MSCT with good diagnostic accuracy. In particular, a high negative
      predictive value of 99% was observed, indicating that 64-slice MSCT may be most
      valuable as a noninvasive method of excluding in-stent restenosis.

PMID- 17543642
TI  - Bicuspid aortic valve morphology and interventions in the young.
AB  - OBJECTIVES: The aim of this study was to determine whether the morphologic
      subtype of bicuspid aortic valve (BAV) is associated with valve intervention in
      the young. BACKGROUND: Analysis of BAV morphology is of prognostic relevance, as
      the fusion of right- and noncoronary leaflets (R-N) is associated with a greater
      degree of valve dysfunction compared with other subtypes. However, it is
      currently unknown whether morphologic differences translate into clinically
      relevant outcomes such as valve intervention. METHODS: A nested cohort study was
      conducted on 310 patients with right- and left-coronary leaflet (R-L) and R-N
      fusion who were selected randomly from an inception cohort of 1,192 patients with
      BAV who were identified between 1986 and 1999. Supplementary information on
      clinical parameters was collected retrospectively from medical charts and
      databases. RESULTS: Median age at follow-up was 16.1 years (range 5.6 to 34.4
      years), and 71% were male. The R-N fusion (n = 108) was strongly predictive of
      valve intervention when compared with The R-L fusion (n = 202; hazard ratio 4.5,
      95% confidence interval [CI] 2.5 to 8.1; p < 0.0001). In a longitudinal analysis
      of 799 echocardiograms, R-N fusion also was associated with a greater progression
      of valve dysfunction. This was true for both increasing aortic valve gradient
      (generalized estimating equations [GEE] risk ratio 27.2, 95% CI 1.2 to 619.6, p =
      0.0386) and aortic regurgitation (GEE risk ratio 2.4, 95% CI 1.3 to 4.3, p =
      0.0029). CONCLUSION: The morphology of BAV is predictive of clinically important
      end points. The R-N fusion is associated with a more rapid progression of aortic
      stenosis and regurgitation and a shorter time to valve intervention.

PMID- 17543643
TI  - Results of the U.S. multicenter pivotal study of the HELEX septal occluder for
      percutaneous closure of secundum atrial septal defects.
AB  - OBJECTIVES: This study sought to compare the safety and efficacy of the HELEX
      septal occluder (HSO) with surgical repair of atrial septal defect (ASD).
      BACKGROUND: The HSO is a low-profile, double-disk occluder device for
      percutaneous closure of secundum ASD. METHODS: Patients were enrolled (HSO arm
      prospectively, surgery arm prospectively/retrospectively) from 14 U.S. sites and
      followed up for 12 months postprocedure. Investigator-reported outcomes were
      evaluated, including closure success (no or clinically insignificant residual
      shunt) and the incidence of adverse events. The first 3 HSO patients at each site
      were considered training cases and were excluded from analysis. RESULTS: Between
      March 2001 and April 2003, 119 nontraining cases received an HSO and 128 had
      surgical repair. The groups were similar with statistical but clinically
      unimportant differences in median age, weight, and preprocedural
      echocardiographic defect size. Anesthesia time and hospital stay were
      significantly shorter in the HSO group. Closure success, defined as complete
      closure or a clinically insignificant residual shunt, was similar in both groups.
      Major and minor adverse events rates were not statistically different. The most
      common major adverse events for the HSO group was device embolization requiring
      catheter retreival (1.7%), and in the surgery group was postpericardiotomy
      syndrome (6.3%), including one death because of tamponade. The primary end point,
      clinical success, a composite of closure success and no major adverse events at
      12 months, satisfied the noninferiority hypothesis comparing device closure with
      surgery. CONCLUSIONS: Closure of ASD with the HELEX septal occluder is safe and
      effective when compared with surgical repair, with reduced anesthesia time and
      hospital stay. (U.S. Multicenter Pivotal Study of the HELEX Septal Occluder for
      Percutaneous Closure of Secundum Atrial Septal Defects; this study was approved
      by the Food and Drug Administration before the National Institutes of Health
      website was active, so there is not a URL or registration number.).

PMID- 17543644
TI  - Device availability for the child with heart disease.

PMID- 17543645
TI  - President's page: drug-eluting stents in contemporary practice--a call for a real
      world, open-entry, device-tracking registry.

PMID- 17543647
TI  - Assessing risk after acute myocardial infarction.

PMID- 17543648
TI  - Hyperthyroidism and mortality.

PMID- 17543650
TI  - The use of the clinical scoring system by Alvarado in the decision to perform
      computed tomography for acute appendicitis in the ED.
AB  - STUDY OBJECTIVE: Appendicitis is part of the differential of an acute abdomen and
      can be a difficult diagnosis to make. Strategies to suggest which patients
      presenting to the emergency department (ED) should undergo computed tomography
      (CT) scan to confirm appendicitis have not been addressed. We develop guidelines
      for CT scanning based on Alvarado clinical scores for patients with suspected and
      confirmed cases of appendicitis. METHODS: A retrospective review of 150 charts of
      patients aged 7 and older who presented with abdominal pain to the ED of a 392
      bed acute care facility over a 6-month period were evaluated by ED physicians and
      underwent CT to rule out appendicitis. Patient demographics, presenting signs,
      and symptoms were documented. Using the scoring system for appendicitis,
      developed by Alvarado, each chart was retrospectively scored. The Alvarado scores
      were correlated with positive pathology findings, as well as Alvarado scores with
      a negative CT scan. Equivocal scores, having neither high sensitivity nor
      specificity for appendicitis were calculated. RESULTS: Computed tomography scans
      with Alvarado scores of 3 or lower were performed in 37% (55/150) of patients to
      rule out appendicitis. The sensitivity of Alvarado scores 3 or lower for not
      having appendicitis was 96.2% (53/55), and the specificity 67% (2/3). Patients
      with Alvarado scores 7 or higher had an incidence of acute appendicitis of 77.7%
      (28/36). The sensitivity of Alvarado scores 7 or higher for appendicitis was 77%
      (28/36), and the specificity 100% (8/8). The sensitivity of equivocal Alvarado
      scores, defined as scores of 4 to 6, for acute appendicitis was 35.6% (21/59),
      and the specificity 94% (36/38). The sensitivity and specificity of CT scans in
      patients with equivocal Alvarado scores remained high, at 90.4% and 95%,
      respectively. CONCLUSIONS: In the equivocal clinical presentation of appendicitis
      as defined by Alvarado scores of 4 to 6, adjunctive CT is recommended to confirm
      the diagnosis in the ED setting. If clinical presentation suggests acute
      appendicitis by an Alvarado score of 7 or higher, surgical consultation is
      recommended. Computed tomography is not indicated in patients with Alvarado
      scores of 3 or lower to diagnose acute appendicitis.

PMID- 17543651
TI  - Statins do not improve short-term survival in an oriental population with sepsis.
AB  - OBJECTIVES: The aim of this study was to define the effect of statin on 30-day
      mortality in an oriental population with sepsis. DESIGN: We conducted a
      retrospective study on patients with sepsis at National Taiwan University
      Hospital from 2001 to 2002. The effects of statins on 30-day mortality were
      evaluated based on clinical settings. Log-rank test and Cox regression analysis
      were performed using the proportional hazards assumption. RESULTS: A total of 763
      episodes of sepsis were reviewed; 454 consecutive patients were considered
      eligible. Among them, 104 (22.9%) took a statin at least 30 days before admission
      and during sepsis course, whereas the other 350 control (77.1%) did not. There
      was no significant difference of 30-day sepsis-related mortality between groups
      (19.2% vs 18.9%, P = .952). Statin treatment was not associated with decreased
      mortality at 30 days (P = .853; risk ratio, 0.95; 95% confidence interval, 0.53
      1.68). CONCLUSION: Short-term, sepsis-related mortality in a septic Taiwanese
      population was not reduced with statin treatment in our study. We concluded that
      statin therapy may have little effect on the survival of sepsis in oriental
      people, particularly in Taiwanese.

PMID- 17543652
TI  - Incidence and risk factors for venous thromboembolism in patients with
      nonsurgical isolated lower limb injuries.
AB  - PURPOSE: The aim of our study was to determine the incidence of venous
      thromboembolism (VTE) in patients with nonsurgical isolated lower limb injury and
      to determine the risk factors associated with the development of the condition.
      METHODS: This observational study was conducted in French hospital emergency
      departments (EDs). Patients older than 18 years presenting with nonsurgical
      isolated lower limb injury below the knee in the ED were included. Deep VTE was
      diagnosed with compression ultrasound. The final diagnosis of VTE was confirmed
      by an expert panel. RESULTS: Three thousand six hundred ninety-eight patients
      were included, and compression ultrasound examination was obtained in 2761 (75%)
      of them who were retained in the analysis. Deep venous thrombosis occurred in 177
      patients and nonfatal pulmonary embolism in 1 patient. The incidence of VTE,
      mainly distal and asymptomatic, was 6.4% (95% confidence interval, 5.5%-7.4%). In
      a multivariate analysis, predictive variables of VTE were age of at least 50
      years (odds ratio, 3.14; P < .0001), rigid immobilization (odds ratio, 2.70; P <
      .0001), no weight bearing (odds ratio, 4.11; P = .0015), and severe injury (odds
      ratio, 1.88; P = .0002). The discriminant analysis showed that age was the only
      variable independent of an antithrombotic prophylaxis associated with VTE.
      CONCLUSION: The incidence of VTE was 6.4% in patients with nonsurgical lower limb
      injury. Rigid immobilization, recommendation not to bear weight, severe injury,
      and age of at least 50 years should be considered as risk factors for VTE.
      Emergency physicians should also take age into account when prescribing
      antithrombotic prophylaxis.

PMID- 17543653
TI  - Epinephrine, but not vasopressin, improves survival rates in an adult rabbit
      model of asphyxia cardiac arrest.
AB  - Although vasopressin has been reported to be more effective than epinephrine for
      cardiopulmonary resuscitation in ventricular fibrillation animal models, its
      efficacy in asphyxia model remains controversy. The purpose of this study was to
      investigate the effectiveness of vasopressin vs epinephrine on restoration of
      spontaneous circulation (ROSC) in a rabbit model of asphyxia cardiac arrest.
      Cardiac arrest was induced by clamping endotracheal tube. After 5 minutes of
      basic life-support cardiopulmonary resuscitation, animals who had no ROSC were
      randomly assigned to receive either epinephrine alone (epinephrine group; 200
      microg/kg) or vasopressin alone (vasopressin group; 0.8 U/kg). The coronary
      perfusion pressure (CPP) was calculated as the difference between the minimal
      diastolic aortic and simultaneously recorded right atrial pressure. Restoration
      of spontaneous circulation was defined as an unassisted pulse with a systolic
      arterial pressure of 60 mm Hg or higher for 5 minutes or longer. We induced
      arrest in 62 rabbits, 15 of whom had ROSC before drug administration and were
      excluded from analysis. The remaining 47 rabbits were randomized to epinephrine
      group (n = 24) and vasopressin group (n = 23). Before and after drug
      administration, CPP in epinephrine group increased significantly (from -4 +/- 4
      to 36 +/- 9 mm Hg at peak value, P = .000), whereas CPP in vasopressin group
      increased only slightly (from 9 +/- 5 to 18 +/- 6 mm Hg at peak value, P = .20).
      After drug administration, 13 of 24 epinephrine rabbit had ROSC, and only 2 of 23
      vasopressin rabbit had ROSC (P < .01). Consequently, we conclude that
      epinephrine, but not vasopressin, increases survival rates in this adult rabbit
      asphyxia model.

PMID- 17543654
TI  - Mortality-related factors after hospitalization for acute exacerbation of chronic
      obstructive pulmonary disease: the burden of clinical features.
AB  - BACKGROUND: There is limited information about factors associated with mortality
      of patients with chronic obstructive pulmonary disease (COPD) admitted to
      hospital because of an acute exacerbation. METHODS: A retrospective cohort study
      including all patients admitted to hospital through our emergency department (ED)
      was conducted. A total of 972 electronic discharge reports were reviewed. Patient
      baseline features, aspects concerning acute exacerbation, as well as demographic,
      cardiac ultrasound, and microbiological data were collected. RESULTS: In-hospital
      mortality rate was 6.4%. Of 315 patients with mild exacerbation according to
      Anthonisen criteria, only 1 died. In the univariate analysis, moderate to severe
      acute exacerbation of COPD, age older than 75 years, severe COPD, abnormal blood
      gas values, onset of complications during hospital stay, radiologic
      consolidation, a positive result in a microbiological respiratory sample, home
      oxygenotherapy, admission to the intensive care unit, left ventricular ejection
      fraction, and department of admission were statistically significant (P < .05).
      The multivariate analysis showed that moderate to severe COPD acute exacerbation
      (odds ratio [OR] 7.3; 95% confidence interval [CI], 3.6-17.7), age older than 75
      years (OR 4.9; 95% CI, 2.3-10.8), severe COPD (OR 4.6; 95% CI, 2.1-10), abnormal
      blood gas values (OR 4.7; 95% CI, 1.1-19.8), and complication during hospital
      stay (OR 2.8; 95% CI 1.4-5.4) were independently related to mortality.
      CONCLUSION: We found that clinical aspect appears the most relevant of all
      potential determinants of in-hospital mortality for patients admitted for acute
      exacerbation of COPD. Thus, the clinical assessment and therapeutic decision
      taken in this first moment at the ED are the key that predict the prognosis of
      this patients. These data suggest that the risk of mortality after the admission
      to hospital of patients with COPD because of an acute exacerbation can be
      successfully predicted by making a clinical assessment at the ED.

PMID- 17543655
TI  - The risk for acute coronary syndrome associated with atrial fibrillation among ED
      patients with chest pain syndromes.
AB  - OBJECTIVE: We sought to determine if atrial fibrillation is associated with an
      increased risk for an acute coronary syndrome (ACS) among emergency department
      (ED) patients with chest pain syndromes. METHODS: We performed a retrospective
      analysis of a prospectively collected database on ED patients with chest pain by
      selecting patients with atrial fibrillation and frequency-matched control
      subjects without atrial fibrillation. Measured outcomes were acute myocardial
      infarction (AMI), ACS, and unstable angina (UA). The relative risks of AMI, ACS,
      and UA associated with atrial fibrillation were calculated. RESULTS: One hundred
      forty patients with atrial fibrillation and 683 matched control subjects were
      identified. The rates of AMI for the atrial fibrillation and control groups were
      11.4% and 10.8%, respectively; those of ACS were 27.9% and 26.7%, respectively;
      and those of UA were 16.4% and 15.8%, respectively. The relative risks of AMI and
      ACS did not increase in patients with atrial fibrillation: AMI, 1.05 (95%
      confidence interval [CI] = 0.63-1.75); ACS, 1.05 (95% CI = 0.78-1.40); and UA,
      1.05 (95% CI = 0.6-1.7). CONCLUSION: Among patients presenting to the ED with
      chest pain syndromes, atrial fibrillation is not associated with an increased
      risk for AMI, ACS, and UA.

PMID- 17543656
TI  - Prevention of awakening signs after rapid-sequence intubation: a randomized
      study.
AB  - BACKGROUND: This study aimed to establish the incidence of signs of inadequate
      sedation after rapid-sequence intubation (RSI) and to determine whether a
      supplementary bolus of induction agent decreases these signs. METHODS: A
      randomized, double-blind trial design was used. Patients were randomly assigned
      to 1 of 2 treatments: RSI plus etomidate bolus followed by continuous sedative
      infusion (ETO group) or RSI plus placebo followed by continuous sedative infusion
      (placebo group). The primary outcome measure was a composite sedation score
      measured 6 minutes after induction. The components of the score were the Ramsay
      sedation score, the presence of cough or pulling at endotracheal (ET) tube, jaw
      relaxation, motor activity, and eye opening. The total score (0-10) was the sum
      of the 5 components. RESULTS: There were 21 patients in the ETO group and 20
      patients in the placebo group. The percentage of patients presenting with at
      least 1 sign of awareness was 43% in the ETO group and 65% in the placebo group
      (P = .16) 6 minutes after induction. The sedation score was significantly higher
      at 6 minutes in the placebo group compared with the ETO group (2.4 +/- 2.9 vs 0.9
      +/- 1.4; P < .05). The use of additional sedative drugs during the observation
      period was 43% (9/21) in the ETO group compared with 55% (11/20) in the placebo
      group (P = .44). CONCLUSIONS: This study demonstrated that some patients have
      signs of inadequate sedation after RSI. These signs may be partially prevented by
      a supplementary dose of an induction agent but other supplementary sedation seems
      necessary.

PMID- 17543657
TI  - Biosurveillance of ED visits for gastroenteritis.
AB  - OBJECTIVE: Our objective was to characterize emergency department (ED) visits for
      gastroenteritis by season and age and develop a predictive model. METHODS: We
      performed a retrospective cohort study of patients seen in 19 EDs from 1988 to
      2002. We examined differences in the annual peaks of younger (<60 months) and
      older (>60 months) age groups and developed a time series regression model.
      RESULTS: Of the 5,182,019 total visits, 88,504 were for gastroenteritis. On
      average, the percentage of gastroenteritis on the peak days was higher in the
      younger (26%) than older group (4%), and the peaks for the younger group occurred
      36 days after those for the older group. CONCLUSION: Emergency department visits
      for gastroenteritis vary greatly by season and age. Our time series predictive
      model was a good fit to actual incidence patterns. These variations should be
      accounted for in designing a system to detect bioterrorism and for surveillance
      of naturally occurring epidemics.

PMID- 17543658
TI  - Risk tolerance for the exclusion of potentially life-threatening diseases in the
      ED.
AB  - OBJECTIVE: Given the same pretest probability (10%) for subarachnoid hemorrhage
      (SAH), pulmonary embolism (PE), and acute coronary syndrome (ACS), we determined
      if differences exist in the risk tolerance for disease exclusion according to
      published guidelines given a negative test result. METHODS: Published guidelines
      that make practice recommendations on the evaluation of ACS, PE, and SAH were
      sought using the National Guideline Clearinghouse in low-risk settings. Second
      order Monte Carlo simulation was performed to determine point estimates and
      confidence intervals (CIs) for posttest probabilities assuming a pretest
      probability of 10%. RESULTS: Guidelines recommend that patients with low-risk
      suspected ACS should undergo stress testing. For SAH, computed tomography (CT)
      followed by lumbar puncture (LP) is recommended without mention of pretest
      probability; and D-dimer testing is recommended to exclude PE in low-risk
      patients. Test sensitivity for thallium-201 single photon emission computed
      tomography (SPECT) was 89%, exercise echocardiogram was 85%, D-dimer testing was
      95%, and CT/LP for SAH was 100% (as a gold standard) and CT only was 97.5%. Given
      a negative test result, for PE, posttest probability was 0.5% (95% CI 0.1%-0.9%);
      for SPECT, 1.1% (SD 0.5%-1.6%); and for exercise echocardiogram, 1.5% (95% CI
      0.5%-2.5%) compared with a posttest probability of 0% for CT followed by LP for
      SAH. Using a CT-only approach gives a posttest probability of 0.2% (95% CI 0.2%
      0.4%). CONCLUSIONS: Guidelines for suspected PE and ACS allow small but nonzero
      calculated risk end points in low-risk settings, whereas SAH guidelines afford no
      misses. Because many gold standard tests are more invasive and can have adverse
      effects, guideline authors should consider adopting a standard acceptable miss
      rate as an end point for workups with low clinical suspicion to avoid the overuse
      of invasive testing.

PMID- 17543659
TI  - Thrombolytic therapy vs primary percutaneous intervention after ventricular
      fibrillation cardiac arrest due to acute ST-segment elevation myocardial
      infarction and its effect on outcome.
AB  - The aim of this study was to evaluate the effect of thrombolytic therapy on
      neurologic outcome and mortality in patients after cardiac arrest due to acute ST
      elevation myocardial infarction and to compare this with those in patients
      treated with primary percutaneous coronary intervention (PCI). We retrospectively
      examined patients after they had ventricular fibrillation cardiac arrests. To
      assess the effect of thrombolysis and PCI on outcome, we used odds ratios and
      their 95% confidence intervals and logistic regression modeling. Thrombolysis was
      applied in 101 patients (69%) and PCI in 46 patients (31%). More patients who
      received thrombolysis had favorable functional neurologic recovery (cerebral
      performance category 1 and 2) and survived to 6 months compared with patients
      with primary PCI (P = .38 and P = .13, respectively). In patients with cardiac
      arrest due to ST-elevation myocardial infarction, it may be acceptable to use
      thrombolysis as a reperfusion strategy. This applies especially in hospitals
      where immediate PCI is not available.

PMID- 17543660
TI  - Hydroxocobalamin for severe acute cyanide poisoning by ingestion or inhalation.
AB  - This chart review was undertaken to assess efficacy and safety of
      hydroxocobalamin for acute cyanide poisoning. Hospital records of the Fernand
      Widal and Lariboisiere Hospitals were reviewed for intensive care unit admissions
      with cyanide poisoning for which hydroxocobalamin was used as first-line
      treatment from 1988 to 2003. Smoke inhalation cases were excluded.
      Hydroxocobalamin (5-20 g) was administered to 14 consecutive patients beginning a
      median 2.1 hours after cyanide ingestion or inhalation. Ten patients (71%)
      survived and were discharged. Of the 11 patients with blood cyanide exceeding the
      typically lethal threshold of 100 micromol/L, 7 survived. The most common
      hydroxocobalamin-attributed adverse events were chromaturia and pink skin
      discoloration. Severe cyanide poisoning of the nature observed in most patients
      in this study is frequently fatal. That 71% of patients survived after treatment
      with hydroxocobalamin suggests that hydroxocobalamin as first-line antidotal
      therapy is effective and safe in acute cyanide poisoning.

PMID- 17543661
TI  - Effects of implementing a rapid admission policy in the ED.
AB  - OBJECTIVE: The purpose of this study is to determine the impact of a new rapid
      admission policy (RAP) on emergency department (ED) length of stay (EDLOS) and
      time spent on ambulance diversion (AD). METHODS: The RAP, instituted in January
      2005, allows attending emergency physicians to send stable patients, requiring
      admission to the general medicine service, directly to available inpatient beds.
      The RAP thereby eliminates 2 conventional preadmission practices: having
      admitting physicians evaluate the patient in the ED and requiring all diagnostic
      testing to be complete before admission. We compared patient characteristics,
      percentage of patients leaving without being seen, EDLOS for admitted patients,
      time on AD, and total adjusted facility charge for a 3-month period after the RAP
      implementation to the same period of the prior year. RESULTS: There was a 1.1%
      increase in census with no difference in patient demographics, acuity, or
      disposition categories for the 2 periods. The EDLOS decreased on average by 10.1
      minutes (95% confidence interval [CI], 3.3-17.0 minutes), resulting in an average
      of 4.2 hours of extra bed availability per day. Weekly minutes of AD decreased
      169 minutes (95% CI, 29-310 minutes). There was also a 3.2% increase (95% CI,
      3.1%-3.3%) in adjusted facility charge between these periods in 2005 compared
      with 2004. CONCLUSIONS: The RAP resulted in a small decrease in the EDLOS, which
      likely decreased AD time. The resulting small increase in ED volume and higher
      acuity ambulance patients significantly improved ED revenue. Wider implementation
      of the policy and more uniform use among emergency physicians may further improve
      these measures.

PMID- 17543662
TI  - Sepsis in the 21st century: recent definitions and therapeutic advances.
AB  - Sepsis as a disease has received renewed interests since recent publications of a
      revised clinical definition and crucial clinical trials showing the benefits of
      early goal-directed resuscitation, recombinant human activated protein C, and low
      dose corticosteroids. The epidemiology of sepsis has also been further examined.
      Management guidelines and international quality improvement efforts have been
      developed targeting increased disease identification, clinician education, and
      optimal patient care with the result of decreasing patient mortality. The
      evidence suggests that early recognition and early intervention are most
      important in affecting outcome. This article will summarize these developments in
      the diagnosis and management of sepsis at the turn of this century.

PMID- 17543663
TI  - Verapamil for ventricular tachycardia.
AB  - Fascicular ventricular tachycardia (VT; also known as left VT) belongs to a
      subclass of idiopathic VTs. It can be confused with VT and supraventricular
      tachycardia. It is an entity well recognized by the cardiology community but not
      as frequently by emergency medicine physicians because of its infrequency.
      Idiopathic left VT was first described in 1979. Belhassen et al were the first to
      report on the characteristic termination of this VT with intravenous verapamil,
      hence accounting for the terms Belhassen VT and verapamil-responsive VT to
      describe the condition. We report on the cases of 2 patients who presented with
      complaints of palpitations. The first patient was incorrectly diagnosed with
      supraventricular tachycardia with aberrant conduction, whereas the second patient
      was correctly diagnosed with fascicular VT. Both cases were medically converted
      with verapamil. We also discuss the differentiation of ischemic VT and fascicular
      VT as well as the related therapeutic options and management approaches.

PMID- 17543664
TI  - Atrial fibrillation in the Wolff-Parkinson-White syndrome: ECG recognition and
      treatment in the ED.
AB  - Estimated to occur in 0.1% to 0.3% of the population, Wolff-Parkinson-White
      syndrome (WPW) is a condition where atrial impulses bypass the atrioventricular
      node and activate the ventricular myocardium directly via an accessory pathway.
      Clinical clues to the diagnosis include a young patient with previous episodes of
      palpitations, rapid heart rate, or syncope. Although several different rhythm
      presentations are possible, atrial fibrillation is a not infrequent dysrhythmia
      seen in the WPW patient. Electrocardiographic features suggestive of WPW atrial
      fibrillation include irregularity of the rhythm; a very rapid ventricular
      response; presence of a delta wave; and a wide, bizarre QRS complex. Stable
      patients suspected of having this condition should not receive agents that
      predominantly block atrioventricular conduction, but they may be treated with
      procainamide or ibutilide. If instability is present, electrical cardioversion is
      required.

PMID- 17543665
TI  - Double counting of heart rate by interpretation software: a new
      electrocardiographic sign of severe hyperkalemia.

PMID- 17543666
TI  - Prehospital noninvasive bilevel positive airway pressure support in a 101-year
      old patient with severe cardiogenic pulmonary edema.

PMID- 17543667
TI  - Qualitative vs quantitative cardiac marker assay in the prehospital evaluation of
      non-ST-segment elevation acute coronary syndromes.

PMID- 17543668
TI  - Statistical or clinical significance? A critical point in interpreting medical
      data.

PMID- 17543669
TI  - Considerations regarding the Spaso technique for dislocations of shoulder.

PMID- 17543670
TI  - Objective scoring systems of medical risk: a clinical tool for selecting patients
      for open or endovascular abdominal aortic aneurysm repair.
AB  - BACKGROUND: Objective scoring systems have been developed for risk stratification
      of open infrarenal aneurysm repair. To date, none have been applied for the
      selection of patients who would most benefit from either an open or an
      endovascular approach. This study assessed the utility of comorbidity-based
      objective scoring systems for defining subgroups of patients who might most
      benefit from open or endovascular aneurysm repair. METHODS: A retrospective
      database review was performed for the period January 1999 to December 2004 to
      identify patients who had undergone elective open aneurysm repair (open repair)
      or elective endovascular aneurysm repair (EVAR). Validation of the Glasgow
      Aneurysm Score (GAS), the Modified Leiden Score (M-LS), and the Modified
      Comorbidity Severity Score (M-CSS) was performed for perioperative mortality risk
      in the open repair group. GAS, M-LS, and M-CSS were then calculated for the EVAR
      group. Differences in open repair vs EVAR mortalities were evaluated. RESULTS:
      During the time period, 558 patients underwent open repair and 304 underwent
      EVAR. Overall mortality was 4.7% for open repair patients and 2.0% for EVAR. All
      three scoring systems were validated to our open repair data set (C statistic:
      GAS, 0.72; M-LS, 0.71; M-CSS, 0.74). A score was calculated for each system that
      separated patients into groups of either low or high risk of death for open
      repair. This score (cut point) was 76.5 for the GAS, 5.2 for the M-LS, and 8 for
      the M-CSS. Analysis of the EVAR population revealed that patients at low medical
      risk for open repair did not derive statistically significant mortality benefit
      with EVAR; however, patients at high medical risk for open repair derived
      significant benefit from EVAR (GAS>76.5 mortality: open repair, 7.8%; EVAR, 1.9%
      [P<.01]; M-LS mortality: open repair, 8.1%; EVAR, 2.5% [P<.01]; and M-CSS
      mortality: open repair, 10.3%; EVAR, 3.4% [P<.025]). Despite a very small number
      of deaths (n=6), receiver operator curve analysis identified M-LS and M-CSS as
      having some predictive ability for mortality risk with EVAR (C statistic: M-LS,
      0.70; M-CSS, 0.69). CONCLUSION: Three validated objective scoring systems can be
      used to categorize patients into two groups of medical risk: one that has
      excellent outcome with open repair and derives no early mortality benefit from
      EVAR, and another that has significant mortality with open repair and derives
      important benefit with EVAR.

PMID- 17543671
TI  - Elevated tissue plasminogen activator in patients with screening-detected
      abdominal aortic aneurysm.
AB  - OBJECTIVE: A population-based case-control study with historical and current data
      was conducted in a population with a high prevalence of disease to explore the
      hypothesis that the fibrinolytic system may be involved in the early pathogenesis
      of abdominal aortic aneurysm (AAA). METHODS: Forty-two patients found to have AAA
      at population-based screening were compared with 100 controls matched for age and
      sex. Mass concentration of tissue plasminogen activator (tPA mass) and tissue
      plasminogen activator/plasminogen activator inhibitor-1 complex (tPA/PAI-1
      complex mass) were analyzed in blood samples obtained at the screening (current),
      and in blood samples obtained from a study conducted 12 years previously on the
      same population (historical). RESULTS: Current tPA mass levels were significantly
      higher in AAA patients compared with controls (13.6 vs 11.4 microg/L, P=.016). A
      similar trend was observed in historical tPA mass levels (9.8 vs 8.2 microg/L,
      P=.062). Current and historical mass concentrations of tPA/PAI complex in AAA
      patients were similar to those in controls. Current tPA mass levels retained the
      associations with AAA in a logistic regression model after adjustment for history
      of atherosclerosis (odds ratio [OR], 1.1 per microg/L, P=.039) and current
      smoking (OR 1.1 per microg/L, P=.039). When family history of AAA was added in a
      logistic regression model, the OR for current tPA mass was 1.1 per microg/L
      (P=.056) and 1.1 per microg/L (P=.070) when treated hypertension was added.
      CONCLUSION: The finding of elevated tPA mass, in contrast to tPA/PAI-1 complex,
      in plasma among patients with screening-detected AAA supports the hypothesis that
      the fibrinolytic system may be important in the early pathogenesis of AAA.

PMID- 17543672
TI  - Effectiveness of intensive medical therapy in type B aortic dissection: a single
      center experience.
AB  - OBJECTIVE: Although the mainstay of managing acute descending thoracic aortic
      dissection (ADTAD) remains medical, certain patients will require emergency
      surgery for complications of rupture or ischemia. This study evaluates factors
      that affect outcome and determines which patients previously treated surgically
      would have been eligible for endovascular repair. METHODS: A single-institution
      retrospective study was conducted of patients who presented with clinical signs
      of ADTAD that was confirmed by magnetic resonance angiography (MRA) or computed
      tomography (CT). All patients were admitted to the intensive care unit (ICU) and
      medically managed to maintain systolic blood pressure<120 mm Hg and heart rate<70
      beats/min. Two treatment groups were identified: group 1 received medical
      treatment only; group 2 received medical treatment plus emergency surgery.
      Patient demographic and clinical data were correlated with 30-day group mortality
      and morbidity and need for emergency surgery. The MRA and CT scan images of group
      2 were retrospectively reviewed to determine if currently available endovascular
      treatment could have been done. The Fisher exact test was used to compare between
      the groups, and P<.05 was considered significant. RESULTS: Between 1991 and 2005,
      83 patients (55 men) were treated for ADTAD. The mean age was 67 years (range, 38
      to 85). Sixty-eight patients (82%) had hypertension, three (3.6%) had Marfan
      syndrome, and 51 (62%) were smokers. Twenty-five (32%) of the patients were
      receiving beta-blocker therapy before the onset of their symptoms. Back pain was
      the most common initial symptom (72.2%). Emergency surgery was required in 19
      patients (23%): 12 for rupture or impending rupture, four for mesenteric
      ischemia, and three for lower extremity ischemia. The need for emergency surgery
      was significantly higher in smokers (P=.03), in patients>70 years old (P=.035),
      and in patients who were not receiving beta-blocker therapy before the onset of
      symptoms (P=.023). The combined overall morbidity rate was 33%, and the mortality
      rate was 9.6%. Morbidity in group 2 was 64% and significantly higher than the 23%
      in group 1 (P=.00227). The mortality rate was also higher in group 2 at 31.5%
      compared with group 1 at 1.6% (P=.0004). Factors affecting the overall mortality
      included age>70 years (P=.057), previous abdominal aortic aneurysm repair
      (P=.018), tobacco use (P=.039), and the presence of leg pain at initial
      presentation (P=.013). As determined from the review of radiologic data, 11 of 13
      patients with scans available for review in group 2 could have been treated with
      currently available endovascular grafts. CONCLUSIONS: Intensive medical therapies
      are effective in preventing early mortality associated with ADTAD. Predictably,
      the need for emergency surgery carries a high morbidity and mortality rate. Most
      patients in this series requiring emergency surgery could have been candidates
      for endovascular therapy had it been available.

PMID- 17543674
TI  - Treatment of type II endoleak with a transcatheter transcaval approach: results
      at 1-year follow-up.
AB  - PURPOSE: This study assessed the feasibility and mid-term outcomes in the
      treatment of type II endoleak using transcatheter transcaval embolization (TTE).
      METHODS: During an 8-month period, 12 patients underwent TTE. After direct
      transcaval puncture of the aneurysm sac, embolization was performed by injecting
      thrombin and placing coils. Systemic and intrasac pressures were recorded
      throughout the entire procedure. Computed tomography (CT) scans were performed at
      24 hours, 30 days, 6 months, and 1 year after TTE to evaluate endoleaks and
      changes in sac diameter. Technical success was defined as the feasibility of the
      procedure; clinical success was defined as no evidence of leaks during the follow
      up evaluation. RESULTS: TTE was feasible in 11 of 12 patients (technical success
      92%). The mean systemic pressure was 117 mm Hg. The mean intrasac pressure before
      embolization was 75 mm Hg (range, 39 to 125 mm Hg), 16.5 mm Hg (range, 7 to 40 mm
      Hg) in 10 patients after embolization, and it increased in one patient. CT scans
      at 24 hours showed stable contrast medium inside the sac in 10 patients. Only
      minor complications were observed during follow-up. At the 1-year follow-up, no
      recurrence of leaks was noted, and sac diameter was reduced in 10 of 11 patients.
      As a result, TTE clinical success was obtained in 10 (83%) of 12 patients.
      CONCLUSION: TTE appears to be a feasible technique for the complete exclusion of
      type II endoleaks. Technical and clinical successes are comparable with other
      treatment strategies, and TTE should be considered an alternative to direct
      translumbar puncture of the aneurysm sac.

PMID- 17543675
TI  - Hybrid approach to thoracoabdominal aortic aneurysms in patients with prior
      aortic surgery.
AB  - OBJECTIVE: The hybrid approach to the repair of thoracoabdominal aortic aneurysm
      (TAAA), consisting of visceral aortic debranching with retrograde
      revascularization of the splanchnic and renal arteries and aneurysm exclusion
      using stent grafts, has been previously described and may be considered
      particularly appealing in high-risk patients, especially those who have undergone
      prior aortic surgery. This study analyzed prospectively recorded data of a series
      of high-risk patients with prior aortic surgery who underwent hybrid TAAA repair
      at our institute and contrasted the outcomes with those of a similar group of
      patients who underwent conventional open TAAA repair. METHODS: Between 2001 and
      2006, 13 patients (12 men) with a median age of 69.6 years (range, 35 to 82
      years) underwent one-stage hybrid repair of TAAA (7 type I, 2 type II, 2 type IV,
      and 2 aneurysms of the visceral aortic patch). These patients, the hybrid group,
      had a history of aortic surgery (30.7% ascending, 30.7% descending, 46.1%
      abdominal aortic repair, and 15.4% redo TAAA) and were at high risk for open
      repair. The criteria used to define these patients as high risk and to indicate
      the need for hybrid treatment were American Society of Anesthesiologists (ASA)
      class 3 or 4 associated with a preoperative forced expiratory volume in 1 second
      (FEV1)<50%. In all cases, we accomplished partial or total visceral aortic
      debranching through (1) a previous visceral artery retrograde revascularization
      with synthetic grafts (single bypass, customized Y or bifurcated grafts), and (2)
      aortic endovascular repair with one of three different commercially produced
      stent grafts (Cook, W.L. Gore & Assoc, and Medtronic). We analyzed the results
      and compared the outcomes of the hybrid group with those of a similar group of 29
      patients (25 men) with a median age 65.3 years (range, 58 to 79) selected from
      our overall series of 246 TAAA repairs between 1988 and 2005. These 29 patients,
      the conventionally treated group, were selected for having had aortic surgery
      (22% ascending, 38% descending, 42% abdominal aortic repair, and 10.3% redo
      TAAA), an ASA 3 or 4, a preoperative FEV1<50%, and a conventional open repair of
      TAAA (10 type I, 5 type II, 4 type III, 7 type IV, and 3 aneurysms of the
      visceral aortic patch). RESULTS: In the hybrid group, 32 visceral bypasses were
      completed and endovascular TAAA repair was successful in all cases. No
      intraoperative deaths occurred. Perioperative mortality was 23%, and morbidity
      was 30.8% (renal failure in 2, respiratory failure in 1, and delayed transient
      paraplegia in 1). At a median follow-up of 14.9 months (range, 11 days to 59.4
      months), all grafts were patent at postoperative computed tomography angiography
      and no aneurysm-related deaths, endoleak, stent graft migration, or morbidity
      related to visceral revascularization had occurred. No conventionally treated
      patients died intraoperatively. Perioperative mortality was 17.2% and morbidity
      was 44.8% (respiratory failure in 7, coagulopathy in 1, renal failure in 2, and
      paraplegia in 3). At a median follow-up of 5.4 years (range, 1.7 to 7.9 years),
      no significant complications related to aortic repair occurred, except for three
      patients (10.3%) with asymptomatic dilatation of the visceral aortic patch<5 cm
      undergoing radiologic surveillance. CONCLUSION: Hybrid TAAA repair is technically
      feasible in selected cases. Perioperative morbidity and mortality were
      considerable in our subset of high-risk patients with prior aortic surgery, but
      no aneurysm-related or procedure-related complications were reported at mid-term
      follow-up. Hybrid TAAA repair did not lead to a significant improvement in
      outcomes compared with open TAAA repair in a similar group of patients. Larger
      series are required for valid statistical comparisons and longer follow-ups are
      necessary to evaluate the durability of hybrid repairs.

PMID- 17543676
TI  - Report on initial experience with transradial access for carotid artery stenting.
AB  - OBJECTIVE: Carotid artery stenting is emerging as an attractive alternative to
      surgical endarterectomy for the treatment of carotid artery disease. This study
      reports our initial experience using the radial artery as access for carotid
      stenting. METHODS: A retrospective study was performed in which 20 consecutive
      patients at high risk for carotid endarterectomy underwent carotid stenting with
      cerebral protection using radial artery access. All procedures were performed in
      the operating room from March 2006 to December 2006. Seven lesions were
      symptomatic, and 13 lesions were asymptomatic. Patients were evaluated for
      development of stroke or transient ischemic attacks, myocardial infarction,
      access site complications, procedural success, time to patient mobilization, and
      need for intravenous analgesia. RESULTS: Procedural success was achieved in 18
      patients (90%). Intense radial artery vasospasm resulted in one failure, and the
      second failure occurred in a patient with a left-sided carotid lesion and type I
      arch. The 30-day incidence of stroke, transient ischemic attacks, myocardial
      infarction, and death was 0%. Radial artery occlusion only occurred in the one
      patient because of the development of intense vasospasm during the procedure. One
      patient had persistent local pain requiring intravenous medication for relief.
      All patients were mobilized <or=2 hours of intervention and were discharged on
      the first postoperative day. CONCLUSIONS: Carotid artery stenting with cerebral
      protection devices can be safely and effectively performed, with acceptable
      morbidity and high technical success, by using radial artery access. We recommend
      obtaining imaging of the aortic arch and supra-aortic trunks with computed
      tomography, as well as a duplex scan of radial artery, before attempting carotid
      artery stenting using radial artery access. Further study is needed before
      recommending that femoral access be replaced by radial access for carotid artery
      intervention.

PMID- 17543677
TI  - Aspirin resistance among long-term aspirin users after carotid endarterectomy and
      controls: flow cytometric measurement of aspirin-induced platelet inhibition.
AB  - BACKGROUND: Numerous studies have indicated that some patient subpopulations do
      not respond to the antithrombotic effects of aspirin. The objective of this study
      was to evaluate aspirin-induced inhibition of platelet cyclooxygenase (COX) using
      a flow cytometric technique in long-term aspirin users after carotid
      endarterectomy (CEA) and controls with newly diagnosed carotid stenosis not
      taking aspirin and to compare these results with platelet function analyzer
      measurements. METHODS: The study included 86 patients with a history of CEA on
      long-term aspirin therapy (100 mg daily) and 29 age-matched patients with newly
      diagnosed carotid artery stenosis not taking aspirin. Platelet-rich plasma
      diluted with phosphate-buffered saline was incubated with arachidonic acid (ARA)
      at a final concentration of 80 micromol/L. After staining with phycoerythrin
      labeled anti-P-selectin (CD62p) antibody, platelet CD62p-antigen expression was
      measured on a flow cytometer. RESULTS: Flow cytometric measurement of ARA-induced
      platelet activation showed an inhibition of ARA-induced platelet stimulation in
      all patients on aspirin therapy, whereas all but two controls (95%) showed
      expected platelet reactivity. In contrast, results of the platelet function
      analyzer measurements were normal in 16% of aspirin-treated patients.
      CONCLUSIONS: Flow cytometric measurement of CD62p expression on platelets after
      incubation with ARA proved to be a practicable tool to monitor aspirin-induced
      inhibition of platelet COX. Results in patients on long-term low-dose aspirin
      therapy show that the inability of aspirin to inhibit platelet COX for both
      symptomatic and asymptomatic patients with high-grade internal carotid artery
      stenosis is a very rare event. So-called aspirin resistance detected quite
      frequently by platelet function analyzer measurement is most likely from COX
      independent mechanisms.

PMID- 17543679
TI  - The value of urgent carotid surgery for crescendo transient ischemic attacks.
AB  - OBJECTIVE: This study audited operative risk in patients undergoing urgent
      carotid surgery for crescendo transient ischemic attacks (TIAs). METHODS:
      Interrogation of the vascular unit database (January 1992 to July 2004)
      identified 42 patients operated on urgently for crescendo TIAs, which were
      defined as>or=3 TIAs within the preceding 7 days. Stroke, death, and any major
      cardiac events were analyzed. RESULTS: Thirty-nine patients underwent
      conventional endarterectomy, and three underwent interposition vein bypass.
      Crescendo TIA patients had sustained a median of five TIAs (range, 3 to 20) in
      the 7 days before surgery. Three patients died or had a stroke after surgery, for
      a combined stroke/death rate of 7%. This compares with 2.4% in 1000 patients
      undergoing elective carotid endarterectomy in this unit during the same time
      period. The combined stroke/death/major cardiac event rate was 14% (n=6).
      CONCLUSIONS: The combined risk of neurologic and cardiac complications after
      urgent carotid surgery for crescendo TIA is higher than that expected after
      elective cases but is still acceptable considering the natural history of
      patients with unstable neurologic symptoms.

PMID- 17543680
TI  - Altered flow territories after carotid stenting and carotid endarterectomy.
AB  - BACKGROUND: The hemodynamic effects of carotid angioplasty with stent placement
      (CAS) on the collateral blood supply and on the regional cerebral blood flow
      (rCBF) have not been established. Recently, arterial spin-labeling (ASL) magnetic
      resonance imaging (MRI) has been introduced as the first method to quantify the
      actual territorial contribution of individual collateral arteries as well as to
      noninvasively measure rCBF. This study investigated alterations in flow
      territories and rCBF in patients with symptomatic internal carotid artery (ICA)
      stenosis and compared them with healthy control subjects. In addition, we
      investigated whether possible differences in flow territories and rCBF were
      present between patients undergoing CAS and patients undergoing carotid
      endarterectomy (CEA). METHODS: The study included 24 consecutive patients (15 men
      and 9 women; age 67+/-9 years) with symptomatic ICA stenosis. CAS was performed
      in 12 patients, and 12 patients underwent CEA. Flow territory mapping and rCBF
      measurements were performed with ASL MRI before intervention and 1 month after.
      The control group consisted of 40 subjects (25 men and 15 women; age 67+/-8
      years). RESULTS: The flow territory of the ipsilateral ICA in patients with ICA
      stenosis was smaller, and the territories of the contralateral ICA and
      vertebrobasilar arteries were larger compared with control subjects (P<.05).
      After CAS, rCBF in the ipsilateral hemisphere increased from 60.2+/-16.9
      mL/(min.100 g) to 68.9+/-9.2 mL/(min.100 g) (P<.05). Differences in flow
      territories and rCBF between patients and control subjects disappeared after CAS.
      Changes in flow territories and rCBF were similar in patients who underwent CAS
      or CEA. CONCLUSIONS: CAS results in a normalization of the territorial
      distribution and rCBF, as assessed by ASL MRI. The degree of improvement is
      similar to that seen after CEA.

PMID- 17543681
TI  - Relationship between temporal-spatial gait parameters, gait kinematics, walking
      performance, exercise capacity, and physical activity level in peripheral
      arterial disease.
AB  - OBJECTIVE: Impaired physical function is a feature of patients with peripheral
      arterial disease (PAD) who present with symptoms of intermittent claudication
      (PAD-IC). Previous research found that temporal-spatial gait parameters do not
      discriminate between PAD-IC patients and control subjects during normal and
      maximal walking even though PAD-IC patients have decreased physical function
      characteristic of the disease. This study examined the hypothesis that patients
      with PAD-IC would demonstrate decreased temporal-spatial gait parameters, gait
      kinematics, walking performance, physiologic responses to exercise, and physical
      activity level compared with control subjects. The aim was to examine the
      temporal-spatial gait parameters and gait kinematics of individuals with PAD-IC
      and to determine the relationship between these variables and walking
      performance, exercise capacity, and physical activity level in these individuals.
      METHOD: A cross-sectional study of 28 PAD-IC subjects (IC) and 25 controls (CON)
      matched for age and mass was conducted in a medical faculty human performance
      laboratory. IC subjects had a history of PAD, ankle-brachial pressure index
      (ABI)<0.9 in at least one leg, and a positive Edinburgh Claudication
      Questionnaire response. Gait characteristics were determined by two-dimensional
      motion analysis. A graded treadmill test was used to assess walking performance
      and peak physiologic responses to exercise. Physical activity levels were
      measured by analysis of 7-day pedometer recording motion. Differences between
      groups were examined by one-way analysis of covariance. RESULTS: Compared with
      CON, IC temporal-spatial gait parameters were significantly lower (P<.05), except
      for single support ipsilateral limb time. IC subjects spent a greater percentage
      of time in gait support phases, took longer to complete a stride, and had reduced
      stride length and walking speeds during the gait cycle. IC joint angular
      kinematics showed significantly reduced displacement of ankle plantar flexion
      (P=.017), knee range of motion (P=.021), and hip extension (P=.016) compared with
      the CON subjects during the gait cycle. All joint minimum and maximum angular
      velocities and accelerations, walking physiologic responses, and physical
      activity levels were significantly lower for IC compared with the CON subjects.
      CONCLUSION: IC subjects walk with a shuffling gait pattern indicated by reduced
      joint angular displacement, velocities, and accelerations that results in reduced
      walking performance and physiologic responses and physical activity compared with
      controls matched for age, mass, and physical activity.

PMID- 17543682
TI  - The treatment of disabling intermittent claudication in patients with superficial
      femoral artery occlusive disease--decision analysis.
AB  - OBJECTIVE: To determine the preferred approach to superficial femoral artery
      (SFA) revascularization of Trans-Atlantic Inter-Societal Consensus (TASC) B and C
      lesions in claudicants requiring intervention based on a review of published
      data. DESIGN: Decision analysis, Markov state transition model. SUBJECTS:
      Hypothetical cohorts of claudicants with TASC B or TASC C superficial femoral
      artery lesions considered candidates for either angioplasty with selective
      stenting (PTA/S) or greater saphenous vein bypass (GSVB). MAIN OUTCOME MEASURE:
      Quality adjusted life years (QALYs). RESULTS: For a 65-year-old man with
      disabling claudication, percutaneous transluminal angioplasty and selective
      stenting (PTA/S) was preferred over GSVB for a TASC B SFA lesion. In an otherwise
      identical patient with a TASC C lesion, bypass was the preferred therapy.
      Treating PTA/S failures with subsequent bypass increased the utility of PTA/S but
      bypass remained the preferred initial therapy for TASC C lesions. Sensitivity
      analysis showed that PTA/S surpasses bypass efficacy for TASC C lesions if PTA/S
      primary patency is >32% at 5 years, patient age is >80 years, or GSVB operative
      mortality is >6%. CONCLUSION: PTA/S is the preferred initial therapy over GSVB
      for TASC B SFA lesions in patients with disabling intermittent claudication who
      require intervention. Given contemporary published outcomes for TASC C lesions,
      GSVB is the preferred therapy in operative candidates. In elderly patients or
      patients at high risk for bypass, PTA/S should be considered over GSVB. Improved
      technology that results in a 5-year primary patency of 32% would also justify
      PTA/S for TASC C SFA lesions.

PMID- 17543683
TI  - A population-based study of peripheral arterial disease prevalence with special
      focus on critical limb ischemia and sex differences.
AB  - OBJECTIVE: A population-based point-prevalence study was conducted to determine
      the prevalence of peripheral arterial disease (PAD) in Sweden, with special
      attention to critical limb ischemia and sex differences. METHODS: An age
      standardized randomly selected population sample of 8000 women and men, aged 60
      to 90 years, from four different regions in Sweden was invited to participate.
      The sample had the same age and gender distribution as the Swedish population in
      this age group. Participating subjects completed questionnaires on medical
      history, present medication, and symptoms, and their ankle-brachial index (ABI)
      was measured. Subjects were analyzed for presence of PAD according to reported
      symptoms and an ABI<0.9. RESULTS: A total of 5080 subjects were included, giving
      a participation rate of 64%. The prevalence of any PAD, asymptomatic PAD,
      intermittent claudication, and severe limb ischemia was, respectively, 18% (95%
      confidence interval [CI], 16% to 20%) 11% (9% to 13%), 7% (6.5 to 7%) and 1.2%
      (1% to 1.5%). Women had a higher prevalence than men when PAD was diagnosed with
      ABI only; that is, asymptomatic PAD (12.6% vs 9.4%, P=.03) and severe limb
      ischemia (1.5% vs 0.8%, P<.008). The prevalence of any PAD was 7.9% in the age
      group 60 to 65 years and increased to 47.2% among the age group 85 to 90 years.
      Severe limb ischemia occurred in 0.3% in the youngest age group, was highest in
      the age group 80 to 84 years at 3.3%, and declined to 2.5% among the oldest. The
      prevalence of PAD differed between regions (P<.0001). CONCLUSIONS: PAD is common
      in Sweden, and almost a fifth of all elderly individuals have some stage of this
      disease. Women are more often afflicted than men. The prevalence of severe
      ischemia, as a measure of critical limb ischemia, is about 1% the population.

PMID- 17543684
TI  - Supervised exercise therapy for intermittent claudication in a community-based
      setting is as effective as clinic-based.
AB  - OBJECTIVE: This cohort study was conducted to determine the effect on walking
      distances of supervised exercise therapy provided in a community-based setting.
      METHODS: The study included all consecutive patients presenting at the vascular
      outpatient clinic with intermittent claudication, diagnosed by a resting ankle
      brachial index<0.9, who had no previous peripheral vascular intervention for
      peripheral arterial disease, no major amputation, and sufficient command of the
      Dutch language. The exclusion criterion was the inability to walk the baseline
      treadmill test for a minimum of 10 m. The intervention was a supervised exercise
      therapy in a community-based setting. A progressive treadmill test at baseline
      and at 1, 3, and 6 months of follow-up measured initial claudication distance and
      absolute claudication distance. Changes were calculated using the mean
      percentages of change. RESULTS: From January through October 2005, 93 consecutive
      patients with claudication were eligible. Overall, 37 patients discontinued the
      supervised exercise therapy program. Eleven stopped because of intercurrent
      diseases, whereas for 10, supervised exercise therapy did not lead to adequate
      improvement and they underwent a vascular intervention. Three patients quit the
      program, stating that they were satisfied with the regained walking distance and
      did not require further supervised exercise therapy. Ten patients were not
      motivated sufficiently to continue the program, and in three patients, a lack of
      adequate insurance coverage was the reason for dropping out. Data for 56 patients
      were used and showed a mean percentage increase in initial claudication distance
      of 187% after 3 months and 240% after 6 months. The mean percentage of the
      absolute claudication distance increased 142% after 3 months and 191% after 6
      months. CONCLUSION: Supervised exercise therapy in a community-based setting is a
      promising approach to providing conservative treatment for patients with
      intermittent claudication.

PMID- 17543685
TI  - The complete management of extremity vascular injury in a local population: a
      wartime report from the 332nd Expeditionary Medical Group/Air Force Theater
      Hospital, Balad Air Base, Iraq.
AB  - BACKGROUND: Although the management of vascular injury in coalition forces during
      Operation Iraqi Freedom has been described, there are no reports on the in
      theater treatment of wartime vascular injury in the local population. This study
      reports the complete management of extremity vascular injury in a local wartime
      population and illustrates the unique aspects of this cohort and management
      strategy. METHODS: From September 1, 2004, to August 31, 2006, all vascular
      injuries treated at the Air Force Theater Hospital (AFTH) in Balad, Iraq, were
      registered. Those in noncoalition troops were identified and retrospectively
      reviewed. RESULTS: During the study period, 192 major vascular injuries were
      treated in the local population in the following distribution: extremity 70%
      (n=134), neck and great vessel 17% (n=33), and thoracoabdominal 13% (n=25). For
      the extremity cohort, the age range was 4 to 68 years and included 12 pediatric
      injuries. Autologous vein was the conduit of choice for these vascular
      reconstructions. A strict wound management strategy providing repeat operative
      washout and application of the closed negative pressure adjunct was used. Delayed
      primary closure or secondary coverage with a split-thickness skin graft was
      required in 57% of extremity wounds. All patients in this cohort remained at the
      theater hospital through definitive wound healing, with an average length of stay
      of 15 days (median 11 days). Patients required an average of 3.3 operations
      (median 3) from the initial injury to definitive wound closure. Major
      complications in extremity vascular patients, including mortality, were present
      in 15.7% (n=21). Surgical wound infection occurred in 3.7% (n=5), and acute
      anastomotic disruption in 3% (n=4). Graft thrombosis occurred in 4.5% (n=6), and
      early amputation and mortality rates during the study period were 3.0% (n=4) and
      1.5% (n=2), respectively. CONCLUSIONS: To our knowledge, this study represents
      the first large report of wartime extremity vascular injury management in a local
      population. These injuries present unique challenges related to complex wounds
      that require their complete management to occur in-theater. Vascular
      reconstruction using vein, combined with a strict wound management strategy,
      results in successful limb salvage with remarkably low infection, amputation and
      mortality rates.

PMID- 17543687
TI  - The effects of stenting and endothelial denudation on aneurysm and branch
      occlusion in experimental aneurysm models.
AB  - BACKGROUND: Stents are increasingly used in the endovascular treatment of
      intracranial aneurysms. We studied the effects of stenting and endothelial
      denudation on aneurysm and branch vessel occlusion. METHODS: Bilateral lingual
      bifurcation venous pouch aneurysms were created in eight dogs, surgically
      scraping the aneurysmal endothelial lining on one side. Both arteries were
      immediately stented using balloon-expandable stents. In four other dogs, a wide
      neck carotid bifurcation aneurysm was created, with the vein pouch denuded or not
      (n=2 each), followed by immediate stenting. Results were compared using
      angiography and pathology at 10 days (n=2), 10 (n=8), and 20 weeks (n=2). Branch
      occlusion between initial and final angiograms was recorded. Pathological
      evaluation of aneurysms was studied, with attention to neointima formation at the
      aneurysm ostium and around branch vessel origins. RESULTS: All stented and
      denuded lingual aneurysms were obliterated compared with two of eight lingual
      aneurysms that were stented alone (P=.007). None of the carotid bifurcation
      aneurysms became obliterated (0/4), but denuded aneurysms showed partial
      thrombosis (2/2). Of 68 total stent-covered branches, 5 (7%) were occluded and 17
      (27%) had altered angiographic flow. CONCLUSIONS: Stenting led to suboptimal
      results in the presence of an intact endothelial layer. Endothelial denudation
      can promote aneurysm occlusion when combined with stenting.

PMID- 17543688
TI  - Blockade of monocyte chemoattractant protein-1 by adenoviral gene transfer
      inhibits experimental vein graft neointimal formation.
AB  - BACKGROUND: Clinical outcome of vascular bypass surgery using autologous vein
      graft is limited by neointimal formation associated with vein graft failure.
      Because inflammatory changes are one of the main pathologic features of vein
      graft failure, monocyte chemoattractant protein-1 (MCP-1) might therefore
      underlie in the mechanism of vein graft failure. There is no direct evidence,
      however, that shows the benefits of local anti-MCP-1 therapy as a novel molecular
      approach for prevention of vein graft failure. METHODS: To block MCP-1, we used
      an N-terminal deletion mutant of the MCP-1 gene (7ND), which lacks the N-terminal
      amino acids 2 to 8, binds to its receptor CCR2, and blocks MCP-1-mediated
      monocyte chemotaxis. 7ND works as dominant-negative inhibitor of MCP-1.
      Autologous canine jugular vein grafts were transfected by incubating them ex vivo
      in a solution with or without adenovirus vectors containing 7ND gene or LacZ
      gene, and interposed into the carotid arteries. RESULTS: Adenovirus-mediated gene
      transfer of 7ND, but not LacZ gene transfer, significantly attenuated
      inflammation (monocyte infiltration per mm2 on day 7: 328+/-59, 220+/-11, 26+/-4
      in control, LacZ, and 7ND groups, respectively, P<.05, n=4 each) and
      proliferation (appearance of proliferating cells per mm2 on day 7: 1005+/-186,
      756+/-106, 252+/-27 in control, LacZ, and 7ND groups, P<.05, n=4 each) at 7 days
      after the operation and thus suppressed neointimal formation (neointimal area in
      mm2 on day 28: 1.63+/-0.51, 1.96+/-0.48, 0.68+/-0.10 in control, LacZ, and 7ND
      groups, P<.05, n=4 each). This strategy also attenuated upregulation of MCP-1
      activities but did not affect endothelial regeneration process. CONCLUSIONS:
      Blockade of MCP-1 by adenoviral gene transfer of 7ND limits neointimal formation
      associated with vein graft failure in dogs. This study highlights the potential
      therapeutic benefit of local anti-MCP-1 therapy for prevention of neointimal
      formation associated with vein graft failure.

PMID- 17543689
TI  - A novel hybrid approach to the treatment of common iliac aneurysms: antegrade
      endovascular hypogastric stent grafting and femorofemoral bypass grafting.
AB  - A progressively enlarging left common iliac artery aneurysm developed in a 72
      year-old man 7 years after open abdominal aortic aneurysm repair with a
      bifurcated Dacron graft. Because both the right hypogastric and inferior
      mesenteric arteries had been ligated at the initial operation, preservation of
      left hypogastric flow was critical to avoid pelvic or intestinal ischemia. He was
      a poor open surgical candidate owing to obesity, a hostile abdomen, and multiple
      medical comorbidities. Therefore, a novel hybrid approach was used consisting of
      left transbrachial selective left hypogastric artery catheterization, followed by
      deployment of two, overlapping, antegrade, covered stent grafts extending from
      the proximal left graft limb into the left hypogastric artery. A right-to-left
      femorofemoral crossover bypass was added to perfuse the left lower extremity and
      was performed in end-to-end fashion to the left common femoral artery to exclude
      and prevent retrograde flow into the iliac aneurysm. Also presented are potential
      procedural pitfalls and a detailed review of open, endovascular and hybrid
      options to preserve hypogastric flow when treating iliac aneurysms in complex,
      high-risk patients.

PMID- 17543690
TI  - Cystic adventitial disease of the popliteal artery: an argument for the
      developmental theory.
AB  - Cystic adventitial disease is a rare non-atheromatous cause of popliteal artery
      disease. We report a case of a 54-year-old patient with claudication of the right
      calf caused by cystic adventitial disease. Intra-operatively, a communication
      between the adventitia and the knee joint was identified. Connections between the
      adventitial cyst and the nearby joint have been reported in the literature that
      support the developmental theory. This theory suggests that cystic adventitial
      disease is a developmental manifestation of mucin-secreting cells derived from
      the mesenchyme of the adjacent joint. This case is the first, to our knowledge,
      in which a communication between joint and adventitia has been clearly documented
      by operative findings.

PMID- 17543691
TI  - Multiple peripheral pneumococcal mycotic aneurysms without aortic involvement: a
      unique case confirmed with the novel use of a molecular diagnostic technique.
AB  - Mycotic aneurysms confer a high morbidity and mortality. Streptococcus pneumoniae
      aneurysms usually affect the aorta and are rare, although bacterial cultures from
      aneurysm tissue may be difficult following prior antimicrobial therapy. We report
      a unique case of mycotic femoral and popliteal artery aneurysms following
      pneumococcal pneumonia and meningitis, which were managed by resection,
      revascularization with autologous vein, and intravenous benzylpenicillin.
      Although blood and aneurysm sac cultures were negative, arterial wall S
      pneumoniae DNA was detected by polymerase chain reaction (PCR). Appropriate
      molecular diagnostic techniques can facilitate diagnosis and direct antimicrobial
      therapy; an important consideration with increasing antimicrobial resistance.

PMID- 17543692
TI  - Spontaneous dissection of the celiac artery: a case report.
AB  - Spontaneous dissection of visceral arteries is rare in the absence of concurrent
      dissection of the aorta, iatrogenic injury from instrumentation, or trauma. We
      describe a spontaneous dissection of the celiac artery that was identified by
      computed tomographic scan in an otherwise healthy man with acute onset abdominal
      pain and no identifiable causes of dissection. The patient was successfully
      managed medically. Although endovascular treatment or surgical intervention is
      the procedure of choice for complicated cases, medical management with close
      observation is an acceptable management strategy for stable, uncomplicated cases
      of spontaneous celiac artery dissection.

PMID- 17543693
TI  - Unusual etiology of upper extremity ischemia in a scleroderma patient: thoracic
      outlet syndrome with arterial embolization.
AB  - Although the causes of digital ischemia and necrosis are diverse in women, the
      most common etiology is connective tissue disease. We describe a patient with
      scleroderma who presented with arm ischemia secondary to arterial embolization
      from thoracic outlet syndrome. Her sublavian artery was compressed by the
      anterior scalene muscle and a cervical rib, leading to a stenosis with
      poststenotic dilation of the artery. Within the aneurysmal formation was a
      thrombus, which was probably the source of the distal embolization. The patient
      underwent surgical resection of the cervical and first rib. The abnormal portion
      of the subclavian artery was resected and replaced with an interposition graft.

PMID- 17543694
TI  - Inferior gluteal artery aneurysm with arteriovenous fistula.

PMID- 17543695
TI  - Use of covered stents and endograft as a rescue treatment in a patient with a
      complex form of recurrent aortic coarctation.
AB  - We report our experience with one patient with recurrent coarctation and aneurysm
      degeneration treated endoluminally. A novel technique was used combining balloon
      expandable with self-expandable endografts. The balloon-expandable component
      expanded the area of stenosis and also created a neck to allow the implantation
      of the self-expandable endograft to exclude the aneurysm. Mismatch of diameters
      was solved with the creation of a new proximal neck, in which the distal end was
      progressively expanded to reach the appropriate diameter to implant the self
      expandable endograft inside. Expansion of the narrow stenosis and complete
      exclusion of the aneurysm was achieved without a residual pressure gradient.

PMID- 17543696
TI  - Screening for abdominal aortic aneurysm in Canada: review and position statement
      of the Canadian Society for Vascular Surgery.

PMID- 17543697
TI  - Presidential address: mind the gap.

PMID- 17543698
TI  - Are ethics practical when externals impact your clinical judgment?

PMID- 17543700
TI  - Regarding "surveillance of small aortic aneurysms does not alter anatomic
      suitability for endovascular repair".

PMID- 17543702
TI  - Regarding "popliteal arterial aneurysm associated with Klippel-Trenaunay
      syndrome: case report and literature review".

PMID- 17543705
TI  - The relevance of social epidemiology in HIV/AIDS and drug abuse research.

PMID- 17543706
TI  - Defining neighborhood boundaries for urban health research.
AB  - The body of literature exploring neighborhood effects on health has increased
      rapidly in recent years, yet a number of methodologic concerns remain, including
      preferred methods for identification and delineation of study neighborhoods. In
      research combining census or other publicly available data with surveys of
      residents and/or street-level observations, questions regarding neighborhood
      definition take on added significance. Neighborhoods must be identified and
      delineated in such a way as to optimize quality and availability of data from
      each of these sources. IMPACT (Inner-City Mental Health Study Predicting
      HIV/AIDS, Club and Other Drug Transitions), a multilevel study examining
      associations among features of the urban environment and mental health, drug use,
      and sexual behavior, utilized a multistep neighborhood definition process
      including development of census block group maps, review of land use and census
      tract data, and field visits and observation in each of the targeted communities.
      Field observations were guided by a preidentified list of environmental features
      focused on the potential for recruitment (e.g., pedestrian volume),
      characteristics commonly used to define neighborhood boundaries (e.g.,
      obstructions to pedestrian traffic, changes in land use), and characteristics
      that have been associated in the literature with health behaviors and health
      outcomes (such as housing type and maintenance and use of open spaces). This
      process, implemented in February through July 2005, proved feasible and offered
      the opportunity to identify neighborhoods appropriate to study objectives and to
      collect descriptive information that can be used as a context for understanding
      study results.

PMID- 17543707
TI  - Social capital or networks, negotiations, and norms? A neighborhood case study.
AB  - "Social capital" has been critiqued as distracting attention from inequalities
      and policies that produce ill health. We support this critique insofar as social
      capital refers to the degree of trust and consensus in a locality, but find value
      in another dimension often included in the concept of social capital--social
      network ties and their associated communication patterns. We present a case study
      of Bushwick, a community of 100,000 people in Brooklyn NY, to suggest that the
      network aspect of "social capital" is useful to understand the active, on-the
      ground processes by which residents of some neighborhoods beset by poverty,
      racial/ethnic subordination, and internal divisions (that themselves arise from
      inequalities and state policies) work out ways to defend their own and others'
      safety and health. We use a combination of population-representative survey data
      for young adults; sexual network survey data; and ethnography to show that
      Bushwick residents (including drug users and dealers) have used social network
      ties, communication, and normative pressures to reduce the extent to which they
      are put at risk by the drug trade and by drug-use-related HIV/AIDS in spite of
      conflicting interests, disparate values, and widespread distrust both of other
      community members and of dominant social institutions. This was done by
      "intravention" health communications, development of protective norms, informal
      negotiations, and other forms of adjustments within and among various groups--but
      it occurred in the absence of trust or consensus in this community. We conclude
      both (1) that social network interpretations of "social capital" might be better
      conceptualized in dialectic terms as collective action to survive in a harsh
      social order, and (2) that the social capital theory emphasis on trust and
      consensus as important causal factors for lowering drug-related risks at the
      community level may be a romanticized and erroneous perspective.

PMID- 17543708
TI  - The formation of a socioeconomic disparity: a case study of cocaine and marijuana
      use in the 1990s.
AB  - BACKGROUND: Around the year 1990, the reputation of cocaine use changed from
      glamorous to undesirable, and at the same time, a socioeconomic disparity in
      cocaine use emerged. This study examined (1) whether the socioeconomic disparity
      was created by differential incidence, differential cessation, or both, (2)
      whether a socioeconomic disparity also developed in marijuana use, and (3)
      whether disparities formed across race, Hispanic ethnicity, and/or gender.
      METHODS: The analyses center on 6544 respondents aged 14-21 in 1979 in the
      National Longitudinal Survey of 1979 that provided information on past-year use
      of powder cocaine and marijuana use before and after 1990--specifically, in 1984,
      1988, 1992, 1994, and 1998. RESULTS: Both differential incidence and differential
      cessation across education contributed to the formation of the socioeconomic
      disparity in cocaine use, although differential cessation played a more
      influential role in this cohort. A socioeconomic disparity in marijuana use also
      came about around the same time. No emerging disparities by race, Hispanic
      ethnicity, or gender were observed. CONCLUSIONS: This case study suggests that
      the redefinition of a health behavior as unhealthy will result in a socioeconomic
      disparity in the behavior across socioeconomic strata as a result of both
      differential incidence and cessation, but disparities will not necessarily form
      by race, ethnicity, or gender.

PMID- 17543709
TI  - Individual action and community context: the Health Intervention Project.
AB  - BACKGROUND: HIV risk-reduction efforts have traditionally focused on the
      individual. The need for including the role of the social context and community
      is being recognized. Social capital provides social relationships and potential
      resources that may hinder or trigger risk or protective health behaviors,
      especially for individuals with limited economic means. METHODS: Sixty-five adult
      inner-city female drug users, who were included in a woman-focused HIV risk
      reduction intervention trial, participated in in-depth interviews in Atlanta,
      Georgia, between 2002 and 2004. The interviews focused on the women's individual
      behavioral changes during the 6 months since completion of the intervention as
      well as on the impact of community conditions. Topics discussed were sexual and
      drug use behaviors, social relationships, social capital, and community physical
      and social infrastructure. The data were analyzed using the constant comparison
      methods. RESULTS: The respondents indicated that poor physical and social
      infrastructure led to alienation and negatively affected their behavioral change
      efforts. Social capital and social support mediated these negative influences.
      Drug-related violence was especially debilitating in their efforts to reduce HIV
      risk associated with crack cocaine or injection drug use and associated sexual
      behavior. Environmental conditions and opportunity structures played salient
      roles in the women's success. CONCLUSIONS: Individual actions and community
      context must be considered simultaneously when facilitating and assessing
      behavioral interventions.

PMID- 17543710
TI  - Religiosity and teen drug use reconsidered: a social capital perspective.
AB  - BACKGROUND: Although religiosity has often been shown to have a deterrent effect
      on teen drug use, noteworthy theoretic gaps and contradictory findings have left
      important questions unanswered. METHODS: Conceptualizing religion as a measure of
      social capital and using cross-sectional data from Monitoring the Future (1996),
      a nationally representative sample of American high school seniors collected
      annually, this study is designed to shed new light on the relationship between
      religiosity and drug use among American youth. Levels of teen drug use for three
      different components of faith-based social capital-exposure to and
      internalization of religious norms, integration within religious networks, and
      trust in religious phenomena-are explored with respect to high school seniors'
      use of alcohol, marijuana, and other illicit drugs during the year prior to the
      survey. In addition, drug use associated with faith-based and secular forms of
      civic engagement among teens (e.g., participation in religious youth groups vs
      secular organizations such as sports and school clubs, theistic trust vs secular
      trust) are compared. RESULTS: Among religiosity variables, integration within
      congregational networks (i.e., worship service attendance) exhibits the most
      consistent negative association with youth drug use. Theistic trust is not
      associated with teen drug use, but secular trust and civic participation in
      secular organizations are associated with less drug use. CONCLUSIONS: Elements of
      both religious and secular social capital are associated with lower reported drug
      use, thereby suggesting that multiple avenues for the prevention of teen drug use
      might be pursued. Implications and directions for future research are discussed.

PMID- 17543711
TI  - Neighborhood income and income distribution and the use of cigarettes, alcohol,
      and marijuana.
AB  - Evidence about the relationship between contextual variables and substance use is
      conflicting. Relationships between neighborhood income and income distribution
      and the prevalence and frequency of substance use in 59 New York City (NYC)
      neighborhoods were assessed while accounting for individual income and other
      socio-demographic variables. Measures of current substance use (in the 30 days
      prior to the survey) were obtained from a random-digit-dial phone survey of adult
      residents of NYC and data from the 2000 U.S. Census to calculate median
      neighborhood income and income distribution (assessed using the Gini
      coefficient). Among 1355 respondents analyzed (female=56.2%, mean age=40.4),
      23.9% reported cigarette, 40.0% alcohol, and 5.4% marijuana use in the previous
      30 days. In ecologic assessment, neighborhoods with both the highest income and
      the highest income maldistribution had the highest prevalence of drinking alcohol
      (69.0%) and of smoking marijuana (10.5%) but not of cigarette use; there was no
      clear ecologic association between neighborhood income, income distribution, and
      cigarette use. In multilevel multivariable models adjusting for individual
      income, age, race, sex, and education, high neighborhood median income and
      maldistributed neighborhood income were both significantly associated with a
      greater likelihood of alcohol and marijuana use but not of cigarette use. Both
      high neighborhood income and maldistributed income also were associated with
      greater frequency of alcohol use among current alcohol drinkers. These
      observations suggest that neighborhood income and income distribution may play
      more important roles in determining population use of alcohol and marijuana than
      individual income, and that determinants of substance use may vary by potential
      for drug dependence. Further research should investigate specific pathways that
      may explain the relationship between neighborhood characteristics and use of
      different substances.

PMID- 17543712
TI  - Neighborhood socioeconomic status, personal network attributes, and use of heroin
      and cocaine.
AB  - BACKGROUND: Drug abuse is a significant public health problem because of its
      association with numerous negative health and social consequences. Examining the
      social context of drug use represents a burgeoning avenue of research in drug
      abuse. This study investigates the effects of neighborhood disadvantage and
      network factors on current heroin and cocaine use among a predominantly African
      American adult sample residing in Baltimore City. METHODS: This study employs a
      cross-sectional, multilevel design using data from two sources: the SHIELD Study,
      a network-oriented HIV intervention in Baltimore City and the 1990 U.S. Decennial
      Census. The sample consisted of 1305 adults from 249 neighborhoods (census block
      groups) across Baltimore City. Multilevel logistic regression analysis was
      performed to examine personal network and neighborhood effects on current heroin
      and cocaine use. RESULTS: Neighborhood poverty was significantly associated with
      current heroin and cocaine use (odds ratio [OR]=1.51, confidence interval
      [CI]=1.06-2.15). Social support (OR=0.80, CI=0.69-0.92) and having ties to
      employed people (OR=0.47, CI=0.24-0.92) were protective of current drug use, but
      did not buffer negative effects of neighborhood poverty in the face of negative
      drug influences in the network (OR=8.62, CI=5.81-12.79). CONCLUSIONS: The
      contexts of neighborhoods and networks represent key determinants in
      understanding the social epidemiology of drug abuse. Network attributes have
      strong influences on drug use, and neighborhood poverty may increase odds of use.
      Further research is warranted to determine other aspects of neighborhood
      environments that may put individuals at risk for drug use and abuse.

PMID- 17543713
TI  - Homelessness and drug use: evidence from a community sample.
AB  - BACKGROUND: Questions regarding the nature of the association between drug use
      and risk of homelessness remain unresolved and have important policy
      implications. METHODS: To address this issue, data are presented from a 2001
      community survey in Chicago, Illinois that collected information regarding
      histories of drug use behaviors and homeless experiences from 627 adults aged 18
      to 40. Using covariance structure analyses, two alternative models of the
      association between drug use and homelessness were evaluated: social selection
      versus social adaptation processes. RESULTS: These findings provide evidence
      consistent with the social adaptation perspective, as early homeless experiences
      were predictive of subsequent drug use behavior in this community sample. Social
      selection processes were observed in bivariate, but not in multivariate,
      analyses. CONCLUSIONS: The role of homelessness as a risk factor for drug use
      initiation should be further explored. Efforts to prevent homelessness may also
      contribute to the prevention of drug abuse.

PMID- 17543714
TI  - Psychiatric comorbidity and acculturation stress among Puerto Rican substance
      abusers.
AB  - BACKGROUND: Although acculturation to the United States has been associated with
      an increase in substance, mood, and anxiety disorders in Latino populations, few
      studies have examined this concept relative to comorbidity among these syndromes.
      METHODS: This study compares the prevalence and patterns of psychiatric
      comorbidity among Puerto Ricans with substance use disorders living in San Juan
      (Puerto Rico) to those who have migrated to New Haven (Connecticut) and examines
      the association between acculturation-related stress and the prevalence and
      patterns of psychiatric comorbidity among those who have migrated to New Haven.
      RESULTS: Lifetime levels of nearly all comorbid psychiatric disorders among
      respondents with substance use disorders were generally similar across sites.
      However, the risk of any co-occurring psychiatric disorder was higher among
      substance use disorder cases in New Haven who reported high levels of total
      acculturation stress and family-specific acculturation stress. These findings
      were generally accounted for by associations between affective disorders and high
      scores on these indicators of acculturation stress. CONCLUSIONS: The overall
      prevalence and patterns of psychiatric comorbidity are remarkably similar among
      Puerto Rican substance abusers whether they live in San Juan or have migrated to
      New Haven, thereby demonstrating robustness to differences in geographic
      location. Nevertheless, the degree of acculturation-related family stress is
      positively associated with co-occurring substance and psychiatric disorders,
      particularly affective disorders. Intervention in family strain related to the
      acculturation process may diminish the development of comorbid mental disorders
      and assist in implementing successful treatment of substance abuse.

PMID- 17543715
TI  - Novel heroin injection practices: implications for transmission of HIV and other
      bloodborne pathogens.
AB  - BACKGROUND: This paper describes injection risk in an out-of-treatment population
      of young heroin users in Hanoi, Vietnam, including use of a soft-tissue portal
      known as a "cay ma" (injection sac). METHODS: Data from a large cross-sectional
      survey (N=1270) are used to describe the prevalence of this practice and its
      association with disease. Additionally, data from an ethnographic substudy on
      injectors serve to elaborate injectors' rationales for this injection practice.
      RESULTS: This practice was common in this sample, appearing soon after initiation
      of habitual injection. Injectors report that this allows rapid and reliable
      access to a vein; strategic advantages in a dense urban environment where rapid
      injection, typically in public settings, is necessary to avoid discovery or
      arrest. Additionally, this practice is believed to mitigate risk for vein damage
      from co-morbid promethazine hydrochloride injection. CONCLUSIONS: This practice
      may draw lymphocytes to injection sites, thereby increasing risk for transmission
      of bloodborne pathogens. Structural and behavioral interventions are needed for
      young heroin users in Vietnam.

PMID- 17543716
TI  - Direct and indirect associations of neighborhood disorder with drug use and high
      risk sexual partners.
AB  - BACKGROUND: On a macrosocial level, neighborhood characteristics have been found
      to be associated with the prevalence of HIV and other bloodborne and sexually
      transmitted infections. The current study used structural equation modeling to
      examine the relationship between neighborhood social and physical disorder and
      high-risk sexual partners. METHODS: A cohort (N=838) recruited for an HIV
      prevention study of drug users (2002-2004) in Baltimore, Maryland, was
      interviewed about their neighborhood characteristics, drug use, depressive
      symptoms (using the Centers for Epidemiological Studies Depression Scale), and
      HIV/sexually transmitted infection risk behaviors of exchanging sex for money or
      drugs, having multiple sexual partners, and having partners who injected drugs or
      smoked crack cocaine. Data were analyzed in February 2005. RESULTS: Model fit
      statistics from Mplus (Muthen & Muthen, Los Angeles CA, 2004) indicated
      statistically significant direct associations between neighborhood disorder and
      psychologic distress, neighborhood disorder and sexual risk behaviors, and
      neighborhood disorder and drug use. There were also significant indirect
      associations of neighborhood disorder on sexual risk behaviors. CONCLUSIONS:
      These results highlight the importance of viewing drug use, chronic stress,
      depression and hopelessness, and infectious diseases such as HIV and hepatitis C
      as interlinked epidemics that are fostered by neighborhood social and physical
      disorder. Neighborhood, network, and community level interventions are needed to
      address these intertwined public health issues.

PMID- 17543719
TI  - Hypogonadotropic hypogonadism.
AB  - Gonadotropin-releasing hormone (GnRH) and olfactory neurons migrate together from
      the olfactory placode, and GnRH neurons eventually reside in the hypothalamus.
      Hypogonadism in male infants may be diagnosed in the first 6 months of life but
      cannot be diagnosed during childhood until puberty occurs. Patients with low
      serum testosterone and low serum gonadotropin levels have idiopathic
      hypogonadotropic hypogonadism (IHH). Mutations in three genes (KAL1, FGFR1, and
      GNRHR) comprise most of the known genetic causes of IHH. Treatment with
      testosterone is indicated if fertility is not desired, whereas GnRH or
      gonadotropin treatment induces spermatogenesis and fertility.

PMID- 17543720
TI  - Diagnostic approach to the infertile male patient.
AB  - There are several objectives to be achieved during the diagnostic evaluation of a
      male partner of an infertile partnership. The first is to identify whether or not
      there is a male factor present and, if so, whether this is attributable to an
      underlying medical illness. The second is to identify the cause of reduced male
      fertility and whether or not it is amenable to therapeutic intervention.

PMID- 17543721
TI  - Medical and surgical management male infertility.
AB  - Male infertility is the result of a variety of highly treatable conditions. The
      critical step in treating male infertility is to evaluate properly every male
      partner of an infertile couple and to generate the proper treatment strategy.
      There are many medical and surgical options that can help most couples overcome
      male factor infertility. Male infertility can most easily be broken down into
      problems of sperm production (testicular dysfunction) and problems of sperm
      transport (obstruction). When applicable, medical therapies are used as an
      initial strategy to improve sperm production or as a preliminary therapy to boost
      production transiently in anticipation of a surgical sperm retrieval attempt. A
      range of surgical options is available to correct varicoceles, reconstruct the
      obstructed system, or retrieve sperm for assisted reproduction.

PMID- 17543722
TI  - Male hypogonadism in systemic disease.
AB  - Hypogonadism is often observed in the presence of common acute and chronic
      illnesses in men. Low testosterone levels in these patients can be associated
      with loss of lean body mass and bone mass density, decline in mood, loss of
      energy, and sexual dysfunction. The mechanisms explaining hypogonadism and
      various systemic diseases are not completely understood, but these conditions are
      likely caused by a combination of stress, nonspecific weight loss, inflammation,
      and medication. Testosterone replacement can be considered in this population to
      improve lean body mass, bone mass density, and quality of life. More information
      is needed regarding the risk benefits of testosterone treatment on health
      outcomes in men who have systemic illness.

PMID- 17543723
TI  - Androgens, obesity, and sleep-disordered breathing in men.
AB  - Impaired gonadal function, obesity, metabolic syndrome, and obstructive sleep
      apnea commonly occur together in men. We propose that this arises due to two
      interlinked cycles. Understanding the molecular mechanisms by which these
      relationships occur may lead to novel therapeutic strategies. Although obesity is
      not gender specific and the effectiveness of current antiobesity interventions
      have predominantly been verified in women, promoting weight loss in men is an
      urgent concern because men are have proportionally worse health consequences. In
      addition, avoiding excessive weight may maintain optimal male reproductive
      health.

PMID- 17543724
TI  - Why men's hearts break: cardiovascular effects of sex steroids.
AB  - Coronary artery disease (CAD) mortality differs in men and women, leading to the
      speculation that differences in sex steroids contribute to risk. Controlled
      clinical trials have shown that estrogen replacement is not cardioprotective in
      certain women, and recent cross-sectional studies associate low testosterone with
      a greater incidence of CAD in men. Testosterone has demonstrated effects on
      insulin resistance, obesity, myocardium, coagulation, inflammation, vasodilation,
      and endothelial function. Imbalance of sex steroids contributes to adverse
      cardiac effects in men.

PMID- 17543725
TI  - Androgenetic alopecia.
AB  - Androgenetic alopecia (AGA), or male pattern hair loss, affects approximately 50%
      of the male population. AGA is an androgen-related condition in genetically
      predisposed individuals. There is no treatment to completely reverse AGA in
      advanced stages, but with medical treatment (eg, finasteride, minoxidil, or a
      combination of both), the progression can be arrested and partly reversed in the
      majority of patients who have mild to moderate AGA. Combination with hair
      restoration surgery leads to best results in suitable candidates. Physicians who
      specialize in male health issues should be familiar with this common condition
      and all the available approved treatment options.

PMID- 17543726
TI  - Osteoporosis in men.
AB  - Osteoporosis has long been considered to be a disease of the aging female
      skeleton. As awareness of the pervasiveness of this disorder increases, it is
      clear that men are also at risk for this disorder. Recent epidemiological studies
      have confirmed that osteoporosis in men is an increasing health problem. This
      development not only has its roots in increased longevity but also in increased
      awareness of this problem in men. The purpose of this article is to review what
      is known about the factors in men that lead to acquisition, maintenance, and loss
      of bone, as well as new insights about the causes, pathogenesis, and treatment of
      osteoporosis in men.

PMID- 17543727
TI  - Hormonal implications in the development and treatment of prostate cancer.
AB  - In this article, the conflicting data concerning the androgen axis and prostate
      cancer development are reviewed in addition to how this pathway may be exploited
      to prevent the development of prostate cancer. The expanding role of hormone
      ablative therapy alone or in conjunction with standard therapies, the
      controversies of timing of therapy, and the completeness of ablation and its use
      on an intermittent basis are reviewed.

PMID- 17543728
TI  - A clinical paradigm for the combined management of androgen insufficiency and
      erectile dysfunction.
AB  - Androgen insufficiency and erectile dysfunction are highly prevalent medical
      disorders in aging men who have associated multiple risk factors. Good clinical
      practice requires the use of appropriate strategies for patient- and goal
      directed diagnosis and treatment. This article focuses on a rational, evidence
      based clinical management paradigm that combines diagnosis and treatment of men
      who have androgen insufficiency and erectile dysfunction.

PMID- 17543729
TI  - ED2: erectile dysfunction = endothelial dysfunction.
AB  - Erectile dysfunction (ED) is a common condition in men, and increases with age.
      Cardiovascular disease (CVD) is the leading cause of death in men and also
      increases in prevalence with advancing years. The common link between the two
      conditions is endothelial dysfunction that leads to vascular insufficiency of the
      coronary and penile arteries. Because the penile arteries are smaller, symptoms
      of ED may precede those of CVD by several years. It is logical, therefore, that a
      patient complaining of ED should alert the physician to look for cardiovascular
      risk factors. Early treatment of these risk factors may help to prevent or retard
      symptoms of vascular insufficiency.

PMID- 17543730
TI  - Treatment options for erectile dysfunction.
AB  - A wide variety of medications, devices, and surgical interventions are available
      to patients who have ED. These range from first-line oral agents to second-line
      therapy with injections or vacuum devices to third-line options, such as penile
      prosthesis implantation. In this article, we cover available treatments for
      erectile dysfunction, ranging from first-line to third-line therapies.

PMID- 17543731
TI  - Performance-enhancing drugs in sport.
AB  - This discussion reviews the concept and history of ergogenic aides, the
      penetration of use in society, some benefit/risk information, drug sources in our
      society, detection and regulation of these agents, and provides a look to the
      future. It also examines the role of the clinician/endocrinologist for these
      patients and uses some cases as examples of drug use among adolescents/teens.

PMID- 17543732
TI  - Gynecomastia.
AB  - Gynecomastia is common and may be asymptomatic. In most cases, a thorough history
      and physical examination, along with limited laboratory investigations, can help
      to exclude breast malignancy and serious underlying endocrine or systemic
      disease. Careful clinical observation may be all that is required in many cases,
      because gynecomastia often resolves spontaneously. Because gynecomastia is
      usually caused by an imbalance of androgenic and estrogenic effects on the
      breast, medical therapy may include antiestrogens, androgens, or aromatase
      inhibitors. Surgery is useful in the management of patients with long-standing
      symptomatic gynecomastia or when medical therapy is not successful.

PMID- 17543733
TI  - Psychosocial aspects of andrologic disease.
AB  - This article reviews the research relating to the psychosocial aspects of
      andrologic disease, focusing on infertility, hypospadias, and erectile
      dysfunction because these diseases draw out the key areas of psychosocial
      interest. This is the case with the development of men who have andrologic
      disease and the problems they face developing relationships. Psychosocial issues
      are often about the perceptions that men and women have regarding androgenic
      disorders rather than the disorder itself. Psychological problems include
      anxiety, depression, and social phobias. In more serious cases, psychological
      problems can affect masculinity, selfhood, and identity. Clinical psychologists
      and other psychotherapists can offer some assistance regarding these perceptions,
      but where there are problems relating to personality and coping styles, these may
      be more difficult to overcome. More research is required to understand the
      specific psychosocial consequences of androgenic disorders.

PMID- 17543734
TI  - Dietary supplements and nutraceuticals in the management of andrologic disorders.
AB  - Dietary supplements and nutraceuticals are commonly used by men with erectile
      dysfunction, decreased libido, BPH, and concerns about developing prostate
      cancer. Many preparations do not contain the advertised dosages of the active
      ingredient or are contaminated. Dietary supplements and nutraceuticals,
      particularly those addressing erectile dysfunction and libido, need to undergo
      rigorous testing before they can be wholeheartedly recommended.

PMID- 17543737
TI  - Impact of left ventricular loading conditions on myocardial deformation
      parameters: analysis of early and late changes of myocardial deformation
      parameters after aortic valve replacement.
AB  - Myocardial deformation imaging is used to assess regional left ventricular (LV)
      function. We sought to define the impact of changes in LV loading conditions on
      myocardial deformation parameters. Aortic valve replacement in patients with
      different aortic valve pathologies was used as a model to assess the impact of
      preload and afterload changes. In 53 patients scheduled for aortic valve
      replacement serial echocardiographic studies were performed preoperatively and
      postoperatively (within 7 days and at 6 months). Parasternal short-axis views
      were acquired. Using novel computer software radial and circumferential strain
      and strain rate were determined as parameters of myocardial deformation for each
      segment of the LV and were subsequently averaged. Immediately postoperatively
      there was a relative increase of radial strain by 4.5 +/- 1.8% after valve
      replacement for aortic stenosis (AS) (P < .001), a relative decrease of 9.4 +/-
      7.7% after valve replacement for aortic regurgitation (aortic insufficiency [AI])
      (P < .001), and unchanged radial strain after valve replacement for AS and aortic
      regurgitation. During the subsequent 6 months of follow-up, there was additional
      relative increase of radial strain by 5.2 +/- 3.1% in the AS group (P < .001), by
      12.0 +/- 13.7% in the AI group (P < .01), and by 5.6 +/- 3.4% in the AS and AI
      group (P < .001). Similar changes were observed for the other strain and strain
      rate parameters. In conclusion, myocardial deformation parameters change
      significantly immediately after aortic valve replacement for AS or AI indicating
      a dependency of determined myocardial deformation parameters on LV preload and
      afterload.

PMID- 17543738
TI  - Intraoperative transesophageal echocardiography using a quantitative dynamic
      loading test for the evaluation of ischemic mitral regurgitation.
AB  - BACKGROUND: Intraoperative transesophageal echocardiography may underestimate
      ischemic mitral regurgitation (MR) as a result of the unloading effect of general
      anesthesia on the left ventricle (LV). An intraoperative loading test could prove
      useful to avoid underestimation of ischemic MR. METHODS: We prospectively studied
      30 patients with ischemic MR referred for coronary artery bypass, mitral valve
      surgery, or both. Transthoracic echocardiography was performed 1.6 +/- 1.6 days
      preoperatively, and intraoperative transesophageal echocardiography after
      induction of general anesthesia before and after LV loading. Preload was adjusted
      using fluids (if pulmonary occlusion pressure < 15 mm Hg), and the afterload
      increased using intravenous phenylephrine aiming at systolic blood pressure of
      160 mm Hg. MR severity was estimated using color Doppler, pulmonary venous flow,
      and the proximal isovelocity surface area method. RESULTS: Preoperative median MR
      grade was 2 (interquartile range 1-3), effective regurgitant orifice area was
      0.16 +/- 0.17 cm2, and regurgitant volume was 23 +/- 23 mL. Intraoperative MR
      grade decreased to 1.5 (1-2.25), effective regurgitant orifice area to 0.13 +/-
      0.16 cm2, and regurgitant volume to 21 +/- 26 mL (P = .02, P = .06, and P = .18).
      After LV loading, MR grade increased to 3 (1-4), effective regurgitant orifice
      area to 0.21 +/- 0.24 cm2, and regurgitant volume to 39 +/- 38 mL (P < or =
      .005). All patients with preoperative +3 MR or greater had +3 MR or greater after
      loading whereas most patients with +1 MR had +1 MR. Of the 11 patients with
      preoperative +2 MR, 6 had +3 and 2 had +4 MR. CONCLUSIONS: A quantitative loading
      test with fluids and phenylephrine is useful to avoid underestimation of ischemic
      MR by intraoperative transesophageal echocardiography, and may detect significant
      MR in some patients who had unloaded LVs and nonsignificant MR during their
      preoperative assessment.

PMID- 17543739
TI  - The crossed swords sign: insights into the dilemma of repair in bileaflet mitral
      valve prolapse.
AB  - BACKGROUND: The need for bileaflet repair in bileaflet mitral valve prolapse
      (MVP) remains controversial. Will anterior leaflet prolapse resolve with
      posterior leaflet repair or should both leaflets be addressed? Single-leaflet MVP
      produces oppositely directed mitral regurgitant jets. Some patients show two
      crossed jets oppositely directed from the coaptation zone. We hypothesized that
      these indicate bileaflet lesions requiring complex repair. METHODS:
      Echocardiograms and surgical reports of 52 consecutive patients with MVP
      undergoing surgery were reviewed. RESULTS: First, all 14 patients with two
      oppositely directed jets had prolapse of more than one leaflet. Each jet was
      related to discrete leaflet distortions causing malcoaptation. Six underwent
      valve replacement. Seven had both leaflets repaired. One had posterior leaflet
      repair and annuloplasty, with persistent mitral regurgitation requiring valve
      replacement. Second, 36 of 38 patients with single jets had single-leaflet MVP.
      One underwent replacement; all others did well with single-leaflet repair. Two
      patients with bileaflet MVP but only one jet did well with single-leaflet repair
      or annuloplasty. CONCLUSION: This crossed swords sign is an important clue to
      bileaflet mechanism of mitral regurgitation in MVP, associated with complex
      repair procedures. Thus, it provides a clue in the dilemma of bileaflet versus
      single-leaflet repair.

PMID- 17543740
TI  - Aortic valve sclerosis: a marker of significant obstructive coronary artery
      disease in patients with chest pain?
AB  - BACKGROUND: Previous reports suggested a relationship between coronary artery
      disease (CAD) and aortic valve sclerosis (AVS). However, whether AVS can be used
      as a marker of obstructive CAD (obCAD) in patients with chest pain is unknown. We
      hypothesized that AVS is a predictive marker for obCAD in patients hospitalized
      for chest pain. METHODS: We studied 93 consecutive patients with chest pain
      undergoing coronary angiography. All had negative cardiac enzymes and no previous
      diagnosis of cardiac ischemic disease. AVS was detected by transthoracic
      echocardiography. Resting electrocardiography, left ventricular systolic
      function, wall-motion abnormalities, and stress test results were considered. We
      calculated the diagnostic value for obCAD of AVS, stress test, and combination of
      the two methods. RESULTS: ObCAD was present in 29 patients (31%). Patients with
      obCAD had a higher prevalence of AVS (38 vs 14%, P = .02) and positive stress
      test (67 vs 28%, P = .02). The odds ratio for obCAD in the presence of AVS was
      3.7 (95% confidence interval 1.3-10.4, P = .01). AVS (P = .01) and a positive
      stress test (P = .002) were independent predictors for obCAD at the multivariate
      analysis. AVS had sensitivity of 38% and specificity of 86%. Stress test had
      sensitivity of 67% and specificity of 72%. When echocardiographic detection of
      AVS was combined with stress test, the sensitivity and negative predictive value
      improved to 93% and 96%, respectively. CONCLUSIONS: AVS is an independent
      predictor for obCAD in patients with chest pain, thus, it should be considered in
      the risk stratification of these patients.

PMID- 17543741
TI  - Evaluation of blood flow reserve in left anterior descending coronary artery
      territory by quantitative myocardial contrast and Doppler echocardiography.
AB  - We sought to compare the feasibility and accuracy of myocardial blood flow
      reserve (MBFR) measured by quantitative real-time myocardial contrast
      echocardiography with those of coronary flow velocity reserve (CFVR) obtained by
      transthoracic Doppler echocardiography for detecting left anterior descending
      coronary artery (LAD) stenosis. We studied 71 patients who underwent adenosine
      stress contrast echocardiography, transthoracic Doppler echocardiography, and
      quantitative coronary angiography within 1 month. An index of myocardial blood
      flow (A x beta) was determined by quantification of peak plateau acoustic
      intensity (A) and microbubble replenishment velocity (beta) by contrast
      echocardiography. Feasibilities of qualitative analysis of myocardial perfusion,
      and CFVR and MBFR measurements were 98%, 83%, and 94%, respectively. Patients
      with LAD stenosis had lower CFVR (1.1 +/- 0.4 vs 2.7 +/- 0.8, P < .001), MBFR
      (1.2 +/- 0.5 vs 2.5 +/- 0.8, P < .001), and beta reserve (1.1 +/- 0.5 vs 2.4 +/-
      0.6, P < .001) than those without lesion. Sensitivities, specificities, and
      accuracies for detecting LAD stenosis were 64%, 93%, and 80% for qualitative
      analysis of myocardial perfusion; 92%, 94%, and 93% for CFVR; 84%, 87%, and 86%
      for MBFR; and 80%, 97%, and 89% for beta reserve. In this selected study
      population, CFVR was the best index for detecting LAD stenosis (odds ratio =
      1.78, 95% confidence interval = 1.28-2.47).

PMID- 17543742
TI  - Objective ischemic evidence in patients with myocardial bridging: ultrasonic
      tissue characterization with dobutamine stress integrated backscatter.
AB  - BACKGROUND: In this study, we investigated the sensitivities of dobutamine stress
      echocardiography (DSE) and integrated backscatter (IBS) in detecting ischemia in
      patients with symptomatic myocardial bridging (MB). METHODS: Fourteen patients
      given the diagnosis of MB in the left anterior descending coronary artery as
      shown by coronary angiography were enrolled. All patients underwent DSE and
      stress IBS. The cyclic variation of IBS (CVIBS) was taken from the
      midanteroseptal, midinferior, and midposterolateral areas of the parasternal
      short-axis images at rest, low dose, peak dose, and recovery. The low-dose, peak
      dose, and recovery CVIBS data were compared with baseline values. RESULTS: At
      peak dose, hypokinesia was observed in the left anterior descending coronary
      artery region in two patients (14%). A significant reduction in CVIBS was
      detected only when compared with the baseline at peak dose in the anteroseptal
      wall (8.4 +/- 1.3 vs 5.9 +/- 0.8, P = .003). A significant negative correlation
      was found between the CVIBS and the systolic narrowing percentage (R = -0.856, P
      = .001) and the length of MB (R = -0.576, P = .01) in the anteroseptal wall at
      peak dose. CONCLUSIONS: Whereas DSE is not sufficiently sensitive in the
      detection of ischemia in patients with symptomatic MB, the reduction in CVIBS
      during DSE may be an objective sign of ischemia.

PMID- 17543743
TI  - No beneficial effects of coronary thrombectomy on left ventricular systolic and
      diastolic function in patients with acute S-T elevation myocardial infarction: a
      randomized clinical trial.
AB  - OBJECTIVE: We sought to evaluate the effect of acute coronary thrombectomy, as
      adjunctive treatment to primary percutaneous coronary intervention, on the
      systolic and diastolic left ventricular function, in patients with acute S-T
      elevation myocardial infarction. METHODS: In a prospective randomized study,
      patients with acute S-T elevation myocardial infarction were randomized to
      treatment with primary percutaneous coronary intervention with or without
      thrombectomy. Outcome measures were left ventricular volumes and ejection
      fraction in addition to systolic long-axis function, estimated from the tissue
      Doppler systolic velocities of the mitral ring. Diastolic function was assessed
      by mitral inflow and diastolic velocities of the mitral ring movement. RESULTS:
      Of the 215 patients included, 172 patients (80%) had a 30-day follow-up. There
      were no significant differences in ejection fraction between groups during follow
      up (thrombectomy at baseline 47 +/- 14% vs 47 +/- 14% at follow-up, control group
      at baseline 48 +/- 11% vs 51 +/- 12% at follow-up, P = not significant). Systolic
      velocities were significantly higher in the control group at follow-up
      (thrombectomy, at baseline, 6.5 +/- 1.9 vs 6.3 +/- 1.8 cm/s at follow-up; control
      group, at baseline, 6.5 +/- 1.9 vs 7.0 +/- 1.9 cm/s at follow-up; P < .05). There
      were no significant differences in diastolic function between the two groups.
      CONCLUSION: Thrombectomy had no beneficial effect on the left ventricular
      function in patients with acute S-T elevation myocardial infarction.

PMID- 17543744
TI  - Influence of age, hypertension, and diabetes on cardiac reserve in a rat model.

PMID- 17543745
TI  - Incremental value of combining systolic mitral annular velocity and time
      difference between mitral inflow and diastolic mitral annular velocity to early
      diastolic annular velocity for differentiating constrictive pericarditis from
      restrictive cardiomyopathy.
AB  - Although normal or exaggerated early diastolic mitral annular velocity (E')
      provides an excellent specificity for differentiating constrictive pericarditis
      (CP) from restrictive cardiomyopathy (RCM), its sensitivity has been shown to be
      lower, especially in patients with CP who had underlying myocardial abnormality.
      This study sought to evaluate the incremental value of systolic mitral annular
      velocity (S') and time difference between onset of mitral inflow and onset of E'
      (T(E'-E)) for differentiation between CP and RCM. This study included 44
      participants (28 male, 16 female; mean age 47 years, range 10-76): 17 patients
      with CP, 12 with RCM, and 15 control subjects. Standard mitral inflow Doppler and
      tissue Doppler echocardiography were performed. E' (9.5 +/- 1.7 vs 4.7 +/- 1.6
      cm/s, P < .001) and S' (7.7 +/- 1.3 vs 4.6 +/- 1.9 cm/s, P < .001) were
      significantly higher, whereas T(E'-E) (21.0 +/- 32.0 vs 53.1 +/- 30.4
      milliseconds, P = .02) was significantly shorter in patients with CP than with
      RCM. Diagnostic accuracy of E' for differentiation of CP from RCM was higher than
      S' or T(E'-E) (area under curve 0.99 vs 0.87 vs 0.74, respectively). E' of 8 cm/s
      had excellent specificity (100%) for differentiation of CP from RCM but
      sensitivity (70%) was relatively low. However, when combining E' with S' and T(E'
      E), the sensitivity could be increased when compared with E' alone (70% with E',
      88% with E' + S', and 94% with E' + S' + T(E'-E)), P = .001). In conclusion, the
      measurement of S' and T(E'-E) can be helpful for differentiating between CP and
      RCM by providing incremental diagnostic information to E'.

PMID- 17543746
TI  - Assessment of left atrial ejection force in hypertrophic cardiomyopathy using
      real-time three-dimensional echocardiography.
AB  - The study included 30 patients with hypertrophic cardiomyopathy (HCM)
      (obstructive and nonobstructive) and 15 control subjects. End-diastolic mitral
      annulus area (MAA(3D)) and mitral valve area (MVA(3D)) were measured by real-time
      3-dimensional (3D) echocardiography. MVA(2D) and peak mitral inflow A wave
      velocity (V) were measured by 2-dimensional (2D) echocardiography. Left atrial
      ejection force (LA-EF) was calculated by 2D echocardiography and real-time 3D
      echocardiography using the formula: 0.5 x 1.06 x (MAA or MVA) x V2, where (1.06)
      is blood viscosity. LA-EF(2D-MVA), LA-EF(3D-MVA), LA-EF(3D-MAA), and V were
      significantly higher in patients with HCM than control subjects (P < .001). LA
      EF(2D-MVA) and LA-EF(3D-MVA) were lower than LA-EF(3D-MAA) in HCM only (P <
      .001). In obstructive HCM, LA-EF(2D-MVA), LA-EF(3D-MVA), LA-EF(3D-MAA), and V
      were significantly higher than in nonobstructive HCM (P < .05). Left ventricular
      outflow tract gradient contributed independently to high LA-EF in obstructive
      HCM. We concluded that HCM is associated with higher LA-EF than normal, and
      higher in obstructive HCM than nonobstructive indicating a higher atrial workload
      that is reflected by LA-EF(3D-MAA).

PMID- 17543747
TI  - The systolic to diastolic duration ratio in children with hypoplastic left heart
      syndrome: a novel Doppler index of right ventricular function.
AB  - BACKGROUND: Right ventricular (RV) function is an important determinant of
      clinical status in children with hypoplastic left heart syndrome (HLHS). However,
      assessment of RV function remains challenging because of its complex morphology.
      We investigated the S/D duration ratio in children with HLHS as a novel index of
      global RV function. METHODS: We measured systolic (S) and diastolic (D) duration
      using tricuspid regurgitation duration from Doppler flow, to calculate the S/D
      ratio in 33 children with HLHS and 33 control subjects matched for age and sex.
      We compared the S/D ratio between patients with HLHS and control subjects,
      between patients with HLHS and normal and abnormal RV function, and between
      patients with HLHS at different stages of palliation. We further correlated the
      S/D ratio with catheterization data. RESULTS: Patients and control subjects were
      well matched for age (3.12 +/- 4.5 vs 3 +/- 4.5 years, not significant) sex, and
      heart rate (cycle length 524 +/- 179 vs 575 +/- 162 milliseconds, not
      significant). Patients with HLHS had a significantly higher S/D ratio than
      control subjects (1.65 +/- 0.85 vs 0.85 +/- 0.2, P < .0001). The S/D ratio became
      increasingly elevated in HLHS at higher heart rates, but not in control subjects.
      The S/D ratio was significantly higher in patients with HLHS and decreased RV
      function as compared with patients with HLHS and normal RV function (2.2 +/- 0.7
      vs 1.5 +/- 0.47, P = .006), and significantly increased in patients with Norwood
      stage 1 versus patients with Norwood stages 2 and 3 HLHS (2.16 vs 1.4 and 1.32,
      respectively, P < .01 and P < .001, respectively). The S/D ratio did not
      correlate with catheterization-derived RV end-D pressure or cardiac index.
      CONCLUSIONS: Patients with HLHS have an increased S/D ratio as a result of a
      shortened D and prolonged S. Measurement of the S/D duration ratio using Doppler
      flow is a novel method to augment assessment of global RV function in HLHS.

PMID- 17543748
TI  - Mechanical dyssynchrony in children with systolic dysfunction secondary to
      cardiomyopathy: a Doppler tissue and vector velocity imaging study.
AB  - OBJECTIVE: Mechanical dyssynchrony is common in adults with heart failure and its
      presence predicts response to cardiac resynchronization therapy. However,
      mechanical dyssynchrony and its quantification by echocardiography have not been
      extensively studied in children with cardiomyopathy. We investigated mechanical
      dyssynchrony in children with systolic dysfunction secondary to cardiomyopathy
      using Doppler tissue imaging (DTI) and vector velocity imaging (VVI). METHODS: We
      used DTI and VVI to quantify mechanical dyssynchrony in 22 children with systolic
      dysfunction secondary to cardiomyopathy and in 25 healthy control subjects. We
      analyzed DTI results corrected for cardiac dimensions and evaluated correlation
      between electrical and mechanical dyssynchrony and between mechanical
      dyssynchrony and systolic function. RESULTS: DTI and VVI revealed significant
      mechanical dyssynchrony among children with cardiomyopathy. Intraventricular and
      interventricular delays as defined by DTI, and the SD of time to peak velocity,
      strain, and strain rate as defined by VVI were 2 to 3 times higher in patients
      with cardiomyopathy as compared with control subjects. There was no significant
      relationship between electrical and mechanical dyssynchrony. CONCLUSIONS:
      Children with systolic dysfunction secondary to cardiomyopathy have mechanical
      dyssynchrony, unrelated to electrical dyssynchrony, which can be measured by
      recent echocardiographic techniques including DTI and VVI. Children with
      cardiomyopathy and mechanical dyssynchrony are potential candidates for cardiac
      resynchronization therapy.

PMID- 17543749
TI  - Right ventricular Tei index in children: effect of method, age, body surface
      area, and heart rate.
AB  - The right ventricular (RV) Tei index (RVTX) has been used to analyze systolic and
      diastolic global RV function in various congenital and acquired cardiac
      abnormalities in children. We conducted a study to determine the effects of the
      methods of Doppler tissue imaging (DTI) versus pulse wave Doppler (PWD) and age,
      body surface area (BSA), and heart rate on the RVTX in a population of 308
      children with normal echocardiogram findings. Participants ranged in age from 1
      day to 18 years, with BSA from 0.08 to 2.4 m2 and heart rate from 46 to 182/min.
      The RVTX was calculated by both DTI and PWD in each patient during a single
      echocardiographic examination. RVTX-DTI = 0.37 +/- 0.05 (mean +/- SD) versus RVTX
      PWD = 0.34 +/- 0.06 were slightly but statistically different (P < .001).
      Univariate linear regression analysis showed age and BSA both had small but
      significant positive effects on both the RVTX-DTI and RVTX-PWD, and heart rate
      had a small but significant negative effect on both techniques (all with P <
      .01). By multivariate regression analysis RVTX-DTI was significantly affected
      only by the BSA and the RVTX-PWD only by age (both with P < .05). Therefore, one
      must consider the method of RVTX measurement, the BSA for RVTX-DTI, and the age
      for RVTX-PWD to accurately assess RVTX values.

PMID- 17543750
TI  - Massive right atrial myxoma presenting as a chronic anemia.

PMID- 17543751
TI  - A heart-shaped mass inside a heart: echocardiographic diagnosis, pathology, and
      surgical repair of a flail tricuspid valve caused by a large blood-filled cyst.

PMID- 17543752
TI  - Unusual intraventricular flow pattern after left ventricular aneurysmorrhaphy.

PMID- 17543753
TI  - Incidental finding of cor triatriatum in an asymptomatic elite athlete.
AB  - Cor triatriatum was diagnosed in an asymptomatic professional football player
      when he underwent cardiovascular evaluation to rule out conditions that can
      potentially cause sudden cardiac death in the young. Cor triatriatum is a rare
      congenital anomaly characterized by failure of resorption of common pulmonary
      vein resulting in division of left atrium into two chambers. Communication
      between the two divided atrial chambers determines the degree of obstruction. In
      this particular case, there were two defects in the membrane, which allowed left
      atrial filling. The filling pressures were not elevated and, hence, the athlete
      was asymptomatic. The literature review has suggested that cor triatriatum has
      been incidentally diagnosed in asymptomatic adults and elderly individuals,
      however, this case demonstrates incidental diagnosis of the condition in an elite
      athlete capable of performing extreme exertion.

PMID- 17543754
TI  - Acute myocardial ischemia associated with latent left ventricular outflow tract
      obstruction in the absence of left ventricular hypertrophy.
AB  - Left ventricular outflow tract obstruction (LVOTO) is a recognized feature in
      hypertrophic cardiomyopathy, but can occur in other clinical scenarios such as
      acute myocardial ischemia. In some patients, LVOTO may only be detectable with
      provocation testing such as exercise stress. Accurate and timely diagnosis,
      therefore, relies on recognizing an echocardiographic substrate in which LVOTO
      may occur, such as ventricular hypertrophy. The investigators describe two cases
      of latent LVOTO, presenting with acute myocardial ischemia in the absence of
      obstructive coronary artery disease, in which the diagnosis was delayed because
      of the absence of hypertrophy, or other recognizable substrate, on the resting
      echocardiographic study, but became evident during exercise echocardiography.

PMID- 17543755
TI  - Silent and huge left ventricular pseudoaneurysm with left atrial compression:
      dedicated spatial resolution and geometry by 3-dimensional echocardiography.
AB  - An 83-year-old man with acute inferior wall myocardial infarction underwent
      successful percutaneous coronary intervention for right coronary artery.
      Subsequent echocardiography 3 days later showed an incidental huge cardiac
      chamber compressing left atrium. The chamber was found to have a narrow neck
      connecting with left ventricle, suggestive of a pseudoaneurysm. Real-time 3
      dimensional echocardiography could clearly demonstrate the spatial relationship
      between pseudoaneurysm and corresponding cardiac chambers, and its precise
      location and the orifice of pseudoaneurysm. A myocardial break-out point
      resembling a bird beak with a flap could also be clearly seen and quantified by
      real-time 3-dimensional echocardiography. This patient underwent surgical
      resection and the serial follow-up remained uneventful.

PMID- 17543756
TI  - Echocardiographic assessment of right heart hemodynamic parameters.
AB  - Echocardiography is currently the primary clinical method for the noninvasive
      measurement of right heart hemodynamic parameters and is an indispensable tool
      for the initial assessment, diagnosis, longitudinal follow-up, and
      prognostication of patients with abnormal right heart function. This review will
      discuss the echocardiographic methods used to estimate right heart hemodynamic
      parameters.

PMID- 17543757
TI  - Devereux formula for left ventricular mass--be careful to use the right units of
      measurement.

PMID- 17543758
TI  - Comparison of regional systolic myocardial velocities in patients with isolated
      left ventricular noncompaction and patients with idiopathic dilated
      cardiomyopathy.

PMID- 17543759
TI  - Abnormal longitudinal myocardial functional reserve assessed by exercise Doppler
      tissue echocardiography in patients with hypertrophic cardiomyopathy.

PMID- 17543760
TI  - Correspondence on "Double atrial septum with persistent interatrial space".

PMID- 17543768
TI  - Physical rehabilitation as an agent for recovery after spinal cord injury.
AB  - The initial level of injury and severity of volitional motor and clinically
      detectable sensory impairment has been considered the most reliable for
      predicting neurologic recovery of function after spinal cord injury (SCI). This
      consensus implies a limited expectation for physical rehabilitation interventions
      as important in the facilitation of recovery of function. The development of
      pharmacologic and surgical interventions has always been pursued with the intent
      of altering the expected trajectory of recovery after SCI, but only recently
      physical rehabilitation strategies have been considered to improve recovery
      beyond the initial prognosis. This article reviews the recent literature
      reporting emerging activity-based therapies that target recovery of standing and
      walking based on activity-dependent neuroplasticity. A classification scheme for
      physical rehabilitation interventions is also discussed to aid clinical decision
      making.

PMID- 17543769
TI  - Acute respiratory infections in persons with spinal cord injury.
AB  - Respiratory disorders are the leading cause of death for persons with both acute
      and chronic spinal cord injury (SCI), and much of the morbidity and mortality
      associated with respiratory disorders is related to acute respiratory infections.
      Pneumonia is the best recognized respiratory infection associated with mortality
      in this population. Recent evidence supports some management strategies that
      differ from those recommended for the general population. Upper respiratory tract
      infections and acute bronchitis may be precipitating factors in the development
      of pneumonia or ventilatory failure in patients with chronic SCI. This review
      emphasizes management principles for treatment and prevention of respiratory
      infections in persons with SCI.

PMID- 17543770
TI  - Pain following spinal cord injury.
AB  - Pain is one of the most common, severe, and treatment-resistant complications
      that follows SCI. Recent years have seen a surge of research on methods for
      assessing and treating spinal cord injury pain. In this article, pain after SCI
      is reviewed in terms of nature, scope, assessment techniques, and treatment
      strategies.

PMID- 17543771
TI  - The prevention and treatment of pressure ulcers.
AB  - Pressure ulcers remain a significant secondary complication for many individuals
      with spinal cord injury (SCI). Technological advances have the potential to
      affect both the prevention and treatment of pressure ulcers. The focus of this
      article is hi-tech devices and methodologies. The current state-of-the-art
      methods are discussed and conceptual approaches are presented.

PMID- 17543772
TI  - Neurogenic bladder in spinal cord injury.
AB  - In the past, renal failure was the leading cause of death after spinal cord
      injury (SCI). Today mortality from SCI has declined dramatically partly owing to
      the improved management of urologic dysfunction associated with SCI. The goals of
      bladder management in spinal cord injury patients are intended to (1) ensure
      social continence for reintegration into community, (2) allow low-pressure
      storage and efficient bladder emptying at low detrusor pressures, (3) avoid
      stretch injury from repeated overdistension, (4) prevent upper and lower urinary
      tracts complications from high intravesical pressures, and (5) prevent recurrent
      urinary tract infections. This article provides an overview of neurogenic bladder
      dysfunction associated with SCI and current management options.

PMID- 17543773
TI  - Autonomic nervous system dysfunction after spinal cord injury.
AB  - The autonomic nervous system (ANS) plays a key role in the regulation of many
      physiologic processes, mediated by supraspinal control from centers in the
      central nervous system. The role of autonomic dysfunction in persons with spinal
      cord injuries is crucial to understand because many aspects of the altered
      physiology seen in these individuals are directly caused by ANS dysregulation.

PMID- 17543774
TI  - Preventive care in spinal cord injuries and disorders: examples of research and
      implementation.
AB  - Individuals with disabilities are less likely to receive preventive care services
      than those in the general population. Prevention is very important in persons
      with spinal cord injuries and disorders for both common conditions such as
      respiratory infections and for conditions common in spinal cord disorders such as
      neurogenic bowel, because these individuals are at increased risk for negative
      outcomes. Clinical practice guidelines provide evidence-based recommendations for
      patient care. However, dissemination of guidelines is not sufficient to increase
      use of recommended care. Implementation research has identified strategies to
      increase use of evidence-based care and subsequently improve patient outcomes.

PMID- 17543775
TI  - Cardiovascular health and fitness in persons with spinal cord injury.
AB  - There are many issues after spinal cord injury that have an impact on
      cardiovascular health and fitness. This article discusses many of the secondary
      conditions and changes that occur and how they are affected by maintenance of an
      active lifestyle. It also discusses many of the benefits and difficulties
      individuals face in maintaining a regular exercise program after spinal cord
      injury.

PMID- 17543776
TI  - Obesity after spinal cord injury.
AB  - America is in the midst of an obesity epidemic, and individuals who have spinal
      cord injury (SCI) are perhaps at greater risk than any other segment of the
      population. Recent changes in the way obesity has been defined have lulled SCI
      practitioners into a false sense of security about the health of their patients
      regarding the dangers of obesity and its sequelae. This article defines and uses
      a definition of obesity that is more relevant to persons who have SCI, reviews
      the physiology of adipose tissue, and discusses aspects of heredity and
      environment that contribute to obesity in SCI. The pathophysiology of obesity is
      discussed relative to health risks for persons who have SCI, particularly those
      contributing to cardiovascular disease. Prevalence of obesity and its
      comorbidities are discussed and management options reviewed.

PMID- 17543777
TI  - Is there a role for proliferation signal/mTOR inhibitors in the prevention and
      treatment of de novo malignancies after heart transplantation? Lessons learned
      from renal transplantation and oncology.
AB  - With the development of new immunosuppressive agents, the majority of transplant
      recipients are surviving for over a decade, and malignancy has become a major
      burden on long-term survival. Reducing the incidence of post-transplant
      malignancies is especially important in heart transplantation where the risk of
      malignancies is higher than in other organ transplants. Everolimus and sirolimus,
      the proliferation signal inhibitors (PSIs) or mammalian target-of-rapamycin
      (mTOR) inhibitors, now provide new strategies for immunosuppression because of
      their proven efficacy that translates to a reduction in doses of calcineurin
      inhibitors needed to prevent acute rejection. In addition, the anti-proliferative
      effects of this class of drugs raise the possibility that they may be effective
      for reducing the risk of malignancies after solid-organ transplantation. Despite
      the paucity of direct clinical evidence for this effect in heart transplant
      patients, observations from renal transplant recipients suggest that the anti
      proliferative actions of PSIs/mTOR inhibitors may also protect against
      malignancies in heart transplant recipients. This potential for an anti-cancer
      effect is further supported by the emerging data on the use of PSIs/mTOR
      inhibitors in non-transplant oncology patients. Reviewed in this article are the
      incidence rates of malignancies after solid-organ transplantation, and the
      evidence for anti-cancer effects of PSIs/mTOR inhibitors in renal transplant
      recipients and in non-transplant patients. Also discussed are the implications of
      these observational data for future studies on the reduction of malignancies
      after heart transplantation.

PMID- 17543778
TI  - Survival in allosensitized children after listing for cardiac transplantation.
AB  - BACKGROUND: Little is known about the effect of pre-transplant alloantibody in
      the pediatric cardiac transplant population. METHODS: All cardiac listings (n =
      298) at Children's Hospital of Pittsburgh from January 1990 through February 2006
      were reviewed to determine the impact of allosensitization on transplantation
      outcomes. Analysis focused on: (1) wait list outcomes; (2) survival from the time
      of listing, regardless of subsequent transplantation; (3) post-transplant graft
      and patient survival; and (4) post-transplant freedom from graft vasculopathy.
      Institutional policy required a negative, prospective crossmatch for candidates
      with panel-reactive antibody >20%. RESULTS: Alloantibody data were available for
      252 (85%) listings. Median time to transplantation was greater for sensitized vs
      non-sensitized subjects (2.7 months vs 1.3 months; p = 0.02). At 1 year after
      listing, sensitized subjects had a higher incidence of death (22% vs 8.4%; p =
      0.055). Survival at all time-points after listing (regardless of transplantation)
      was worse for sensitized subjects (p = 0.04). Although no statistically
      significant differences in post-transplant graft or patient survival were noted,
      pre-transplant allosensitization was associated with decreased freedom from graft
      vasculopathy (hazard ratio [HR] 2.76, 95% confidence interval [CI] 1.18 to 6.45;
      p = 0.019). CONCLUSIONS: A policy requiring a negative, prospective crossmatch
      for highly sensitized candidates is associated with longer wait list time and
      higher mortality after listing. The development of graft vasculopathy appears to
      be influenced by the presence of pre-transplant alloantibody.

PMID- 17543779
TI  - Choroidal microcirculation in patients with rotary cardiac assist device.
AB  - BACKGROUND: In recent years, fully implanted rotary blood pumps have been used
      for long-term cardiac assist in patients with end-stage heart failure. With these
      pumps, the pulsatility of arterial blood flow and arterial pressure pulse is
      considerably reduced. Effects on end-organ perfusion, particularly
      microcirculation, have been assessed. METHODS: The ocular choroid offers a unique
      opportunity to study the pulsatile component of blood flow by measurement of
      fundus pulsation amplitude (FPA) as well as the microcirculation by laser Doppler
      flowmetry. Both techniques were applied in three male patients with rotary pumps
      (MicroMed DeBakey VAD), in whom pump velocity was adjusted to four levels of flow
      between individual minimal need and maximal support. In addition, blood flow
      velocities in the ophthalmic artery (peak, end-diastolic and mean flow velocity-
      PSV, EDV and MFV, respectively) were measured using color Doppler imaging.
      RESULTS: Systolic blood pressure increased by 6 to 22 mm Hg with increasing
      support. At maximal support FPA was reduced by -60% to -52% as compared with
      minimal pump support. Blood flow in the choroidal microvasculature, however, did
      not show relevant changes. A reduction in PSV (-31%, range -47% to -21%) and a
      pronounced rise in EDV (+93%, range +28% to +147%) was observed, whereas MFV was
      independent of pump flow. CONCLUSIONS: Our data indicate that mean choroidal
      blood flow is maintained when pump support is varied within therapeutic values,
      whereas the ratio of pulsatile to non-pulsatile choroidal flow changes. This
      study shows that, in patients with ventricular assist devices, a normal perfusion
      rate in the ocular microcirculation is maintained over a wide range of support
      conditions.

PMID- 17543780
TI  - Utilization of acoustic signatures to identify HeartMate XVE device end-of-life.
AB  - BACKGROUND: As outcomes for destination therapy continue to improve, many
      patients are requiring left ventricular assist device (LVAD) exchange due to end
      of-life of their LVAD. Current techniques to identify and diagnose device end-of
      life issues usually require invasive testing or off-site filter dust analysis. In
      this study we assess a non-invasive technique using acoustic signals generated
      from the HeartMate XVE LVAD to potentially identify impending device end-of-life
      issues. METHODS: Nine patients were prospectively followed after implantation of
      the HeartMate XVE LVAD as destination therapy between May 2004 and July 2006.
      Acoustic signals were collected using an aquatic hydrophone system interfaced
      with a data acquisition system and a standard laptop computer. Data were
      collected at pre-set intervals. All data/acoustic signals were prospectively
      interpreted by a blinded independent reviewer skilled at interpreting acoustic
      signals. Acoustic data suggesting possible device failure were then correlated
      with clinical findings and LVAD examination at the time of device removal.
      RESULTS: All patients survived long enough to develop signs of impending device
      end-of-life. Four of 9 (44%) patients developed inflow valve incompetence, 4
      (44%) were identified as having significant bearing wear, and 1 (12%) had both.
      All acoustically identified device issues were confirmed by standard clinical
      examinations and testing (echocardiography, angiography, laboratory tests and
      filter dust analysis). The acoustic findings were subsequently confirmed at time
      of device exchange. All patients ultimately had their device successfully
      exchanged and have continued to live with their new apparatus. CONCLUSIONS:
      Acoustic signal monitoring can successfully identify HeartMate XVE device end-of
      life. This new method provides a low-cost, reproducible, non-invasive technique
      that may be used to identify possible impending device failure.

PMID- 17543781
TI  - Prevention of acute rejection and allograft vasculopathy by everolimus in cardiac
      transplants recipients: a 24-month analysis.
AB  - BACKGROUND: Everolimus is an immunosuppressive agent that reduces cardiac
      allograft vasculopathy. This report presents the 24-month results of a
      multicenter trial of everolimus vs azathioprine in heart transplantation.
      METHODS: A total of 634 patients were randomized to receive 1.5 mg everolimus, 3
      mg everolimus or azathioprine, with cyclosporine and steroids. A 12-month, double
      blind, double-dummy period was followed by a 12-month open-label period. RESULTS:
      At 24 months, the percentage of patients reaching the composite efficacy end
      points was significantly lower with everolimus (1.5 mg: 45.9%, p = 0.016; 3 mg:
      36.0%, p < 0.001) than with azathioprine (57.5%). The change in maximal intimal
      thickness from baseline to 24 months was significantly smaller with everolimus
      1.5 mg (0.07 mm, p = 0.014) and 3 mg (0.06 mm, p = 0.004) compared with
      azathioprine (0.15 mm). The 24-month incidence of vasculopathy was 33.3% with
      everolimus 1.5 mg, 45.5% with everolimus 3 mg and 58.3% with azathioprine (p =
      0.017 vs everolimus 1.5 mg). Incidence of cytomegalovirus infection was 3-fold
      lower in patients receiving everolimus compared with azathioprine (7.2% and 7.1%
      in the 1.5-mg and 3-mg everolimus cohorts, respectively, and 21% in the
      azathioprine group; p < 0.0001). Median serum creatinine levels at 24 months were
      higher with everolimus than with azathioprine, but decreased when cyclosporine
      exposure was reduced (everolimus 1.5 mg: baseline 167 micromol, after 6 months
      157.5 micromol; everolimus 3 mg: baseline 185.6 micromol, after 6 months 160
      micromol; azathioprine: baseline 123.3 micromol, after 6 months 127 micromol).
      CONCLUSIONS: Everolimus significantly reduced acute rejection and limited the
      progression of allograft vasculopathy at 24 months compared with azathioprine.
      Although graft and patient survival was comparable at 24 months, everolimus
      therapy may improve longer-term outcomes after heart transplantation.

PMID- 17543782
TI  - Coronary angiography for follow-up of heart transplant recipients: insights from
      TIMI frame count and TIMI myocardial perfusion grade.
AB  - BACKGROUND: The aim of this study was to evaluate the course of Thrombolysis in
      Myocardial Infarction (TIMI) frame count (TIMI FC) and myocardial perfusion grade
      (TIMI MPG) in heart transplant recipients and whether these parameters could
      predict mortality. METHODS: Sixty-two heart transplant recipients were enrolled
      in this study. All patients had coronary angiography at baseline and at 1 year,
      which were evaluated for TIMI FC and TIMI MPG. Also, 50 vessels in 35 patients
      were analyzed with volumetric intravascular ultrasound (IVUS) at baseline and at
      1 year. Rejection episodes and mortality were recorded during the follow-up
      period. RESULTS: The mean follow-up interval was 51.5 +/- 17.2 months (range 12.2
      to 78.4 months). TIMI FCs of all three coronary arteries and global TIMI FC
      (gTIMI FC) significantly increased from baseline during the first year (p <
      0.0001). TIMI MPG deteriorated significantly (p < 0.0001 for left anterior
      descending and circumflex coronary arteries, p = 0.002 for right coronary
      artery). There was no correlation between changes in TIMI FC and progression of
      transplant vasculopathy as assessed by IVUS. Episodes of Grade > or = 3A
      rejection were significantly more frequent in the stable gTIMI FC group (p =
      0.03). Mortality rate was significantly higher in the group with increasing gTFC
      (p = 0.02). CONCLUSIONS: gTIMI FCs and TIMI FCs of coronary arteries increase,
      and TIMI MPG gradually deteriorates during the first year after transplantation.
      Mortality rate is significantly higher in patients whose gTIMI FC increases from
      baseline. Change in gTIMI FC is a simple quantitative predictor of long-term
      mortality in heart transplant recipients.

PMID- 17543783
TI  - Low-dose tacrolimus/sirolimus and steroid withdrawal in heart recipients is
      highly efficacious.
AB  - Heart transplant recipients treated with long-term calcineurin inhibitors (CNIs)
      experience significant nephrotoxicity and transplant vasculopathy. Signal
      proliferation inhibitors might prevent the development of transplant
      vasculopathy. In an open, prospective pilot study, 33 primary heart transplant
      recipients received tacrolimus (Tac) and sirolimus (rapamycin, Rapa) with
      steroids. To reduce both nephrotoxicity and transplant vasculopathy at the same
      time, both Tac and Rapa exposure was kept low (6 to 8 ng/ml). Steroids were
      withdrawn successfully from all patients within 6 months. Just one acute
      rejection occurred at 54 days post-transplant, resulting in 0.03 acute rejection
      episode per patient at 1-year (primary end-point) and 2-year follow-up.
      Transplant vasculopathy assessed by angiogram was absent at 2 years. Graft and
      patient survival were 100% at 1 and 2 years. Accordingly, the survival estimate
      for freedom from first acute rejection, transplant vasculopathy, graft loss or
      death was 0.97 at 1 and 2 years. The regimen was well tolerated with only 3
      patients requiring a change of study medication. Mean serum creatinine increased
      during the first year but returned to baseline at 2 years.

PMID- 17543784
TI  - Post-conditioning protects from cardioplegia and cold ischemia via inhibition of
      mitochondrial permeability transition pore.
AB  - BACKGROUND: The aim of this study was to evaluate the role of the mitochondrial
      permeability transition pore (MPTP) in the protection achieved by post
      conditioning of hearts submitted to hypothermic cardioplegia and ischemia.
      METHODS: Isolated rat hearts (n = 30) underwent cold cardioplegia (4 degrees C,
      Celsior solution) and 8 hours of ischemia at 4 degrees C, followed by a 60-minute
      Langendorff reperfusion. Hearts were randomly assigned to one of two groups: post
      conditioning (post-C, consisting of episodes of 30-second ischemia and 30-second
      reperfusion at onset of reperfusion) or control (no intervention). A sham group
      was added for which hearts were harvested and immediately reperfused without
      ischemia. Coronary flow, heart rate, dP/dt and rate-pressure product were
      measured. Infarct size was assessed by triphenyltetrazolium chloride (TTC)
      staining and lactate dehydrogenase (LDH), creatine phosphokinase (CPK) and
      troponin I release analysis. After reperfusion, heart mitochondria were isolated
      and calcium overload necessary to induce MPTP opening was measured. From the
      onset of reperfusion, all functional parameters were significantly improved in
      post-C vs control hearts. RESULTS: Infarct size, measured both by TTC staining
      and LDH, and CPK and troponin I leakage were lower in post-C hearts (p < 0.01).
      Mean calcium load needed to induce MPTP opening was higher in post-C mitochondria
      vs controls (p < 0.01). CONCLUSIONS: Post-conditioning protects the rat heart
      against cold ischemia-reperfusion injury. Our data suggest that this protection
      involves inhibition of MPTP opening.

PMID- 17543785
TI  - Canine bilateral lung transplantation after 18-hour preservation using non-heart
      beating donors.
AB  - BACKGROUND: We previously reported that lung inflation with oxygen, EPC-K1 (a
      diester alpha-tocopherol and ascorbic acid), urokinase and low-potassium dextran
      glucose (LPDG) solution can be beneficial in lung preservation. In the present
      study, a canine bilateral lung transplantation (BLT) model was used to evaluate
      long-term lung preservation of non-heart-beating donors (NHBDs). METHODS: Animals
      were euthanized without heparinization and left at room temperature for 2 hours
      until lung extraction. After cardiac arrest, the lungs were kept inflated with
      100% oxygen. After extraction, the donor lungs were flushed with LPDG solution
      containing EPC-K1 (1.0 mg/liter), followed by injection of urokinase (120,000 IU)
      into the pulmonary artery. Eighteen BLTs were performed after preservation at 4
      degrees C. Total ischemic time was scheduled for 12 hours in Group 1 (n = 6), 18
      hours in Group 2 (n = 6) and 24 hours in Group 3 (n = 6). After BLT, recipients
      were followed up for 6 hours. An additional 6 BLTs were performed as a chronic
      study in the same setting as for Group 2. RESULTS: All animals in Groups 1 and 2
      showed excellent pulmonary function during the 6-hour post-transplant assessment
      time, in contrast to only 2 dogs from Group 3. In the chronic study, all 6
      animals showed excellent pulmonary function for 24 hours (PaO2 = 528 +/- 8 mm Hg
      with 100% oxygen) and 2 of them survived for >1 week. CONCLUSION: Successful
      chronic lung preservation (18 hours) using NHBDs is achievable in a canine BLT
      model.

PMID- 17543786
TI  - What maintains the metabolic cost at maximal exercise in heart transplant
      recipients and coronary artery disease patients?
AB  - BACKGROUND: In this study we assess the influence of disease status on
      hemodynamic and cardiac output values, as measured by oxygen utilization at peak
      aerobic exercise, in heart transplant recipients (HTRs) and coronary artery
      disease patients (CAD). METHODS: Fifteen CAD patients and 13 HTRs (40.2 +/- 12.6
      and 41.7 +/- 11.7 years, respectively) underwent a peak cardiopulmonary exercise
      test on bicycle ergometry. Arterial oxygen was defined on the basis of
      echocardiography and venous oxygen content. RESULTS: At rest, except for cardiac
      output, oxygen uptake and lactate levels, all variables were significantly (p <
      0.01) different between groups. At peak exercise, compared with HTRs, CAD
      patients had significantly (p < 0.0001) higher values for cardiac output (12.4 +/
      0.8 and 20.2 +/- 1.7 liters/min, respectively), stroke volume (87.3 +/- 5.4 and
      129.3 +/- 9.7 ml, respectively) and oxygen uptake (22.7 +/- 3.6 and 29.7 +/- 2.7
      ml/kg/min, respectively) (p < 0.01), whereas (a - v)O2 was significantly lower
      (127.0 +/- 4.3 and 141.9 +/- 6.4 O2 ml/liter, respectively; p < 0.0001).
      CONCLUSIONS: The differences in oxygen utilization at peak exercise may be
      attributed to differences in energy metabolism, namely higher oxygen extraction
      in HTRs, compensating for the dramatically reduced oxygen delivery. It is further
      suggested that CAD patients and HTRs respond to a greater extent to maximal
      aerobic testing by reducing their left ventricular systolic function despite
      increased after-load.

PMID- 17543787
TI  - Cytokine activation and disease progression in patients with stable moderate
      chronic heart failure.
AB  - BACKGROUND: Activation of the cytokine and the complement system is associated
      with disease progression in severe congestive heart failure (CHF). Magnitude and
      prognostic relevance of cytokine and complement activation remain uncertain in
      patients with moderate CHF. OBJECTIVES: Measurement of cytokine and complement
      activation in patients with moderate CHF and testing whether C-reactive protein
      (CRP) can serve as a surrogate marker of their activation, adding independent
      prognostic information when co-measured with B-type natriuretic peptide (BNP).
      METHODS: The 118 study participants were separated into three groups based on pre
      determined CRP and BNP levels: Group I (n = 27; CRP > 5 mg/liter, BNP > or = 200
      pg/ml); Group II (n = 46; CRP < or = 5 mg/liter, BNP > or = 200 pg/ml); and Group
      III (n = 45; CRP < or = 5 mg/liter, BNP < 200 pg/ml). RESULTS: Mortality was high
      in Group I (30%; log-rank p < 0.001) but low in Groups II and III (2% and 4%,
      respectively; log rank, p = 0.7). No differences were observed for left
      ventricular ejection fraction (LVEF) and left ventricular end-diastolic diameter
      (LVEDD) between Groups I and II (31 +/- 16 vs 32 +/- 14% and 66 +/- 16 vs 65 +/-
      11 mm, respectively), whereas in Group III LVEF was higher (42 +/- 17%, p =
      0.002) with smaller LVEDD (57 +/- 13 mm, p = 0.012). Cytokine sCD14 and tumor
      necrosis factor (TNF)-alpha levels were not different between the three groups.
      However, interleukin-6 levels (9.75 +/- 8.17 pg/ml, p = 0.001) and the terminal
      complement complex C5b-9 (109.9 +/- 68 ng/ml; p = 0.04) were elevated in Group I,
      both correlating with CRP (interleukin-6: r = 0.5, p < 0.001; C5b-9: r = 0.41, p
      = 0.001). CONCLUSIONS: CRP may be used as a surrogate parameter for interleukin-6
      and complement activation in moderate CHF. CRP in combination with BNP identifies
      a high-risk group with a tendency for poor outcome not discriminated by cardiac
      function.

PMID- 17543788
TI  - Cardiac myocyte transplantation does not increase global epicardial
      repolarization heterogeneity in a rat infarct model.
AB  - BACKGROUND: Using a rat in vivo infarct model we tested the hypothesis that fetal
      cardiomyocyte (FCM) implantation would increase repolarization heterogeneity.
      METHODS: Four groups of rats were studied: two groups served as controls and
      underwent injection with FCM or culture medium in a region of the left ventricle
      (LV) supplied by the left anterior descending artery (LAD), and two groups
      underwent LAD ligation followed 3 weeks later by the injection of either FCM or
      culture medium. Epicardial monophasic action potential (MAP) recordings were
      obtained 4 to 5 weeks after cell injection from the right ventricle (RV), LV
      infarction region and LV region remote from the LAD. The maximum difference in
      action potential duration (MAPD90) between the three sites was defined as
      repolarization heterogeneity. RESULTS: LAD ligation (in the control media
      injection group) resulted in an increase in repolarization heterogeneity from 6.9
      +/- 0.9 to 13.8 +/- 1.2 ms (p < 0.005). Similarly, injection of FCM without
      coronary ligation resulted in an increase in heterogeneity from 6.9 +/- 3.9 to
      20.7 +/- 1.3 ms (p = 0.001). However, injection of FCM into regions of infarction
      did not result in an increase in heterogeneity when compared with the control
      media group (13.8 +/- 1.9 vs 13.0 +/- 2.6 ms, respectively, p = 0.752).
      CONCLUSIONS: Both fetal cardiomyocyte engraftment in the normal myocardium and
      coronary ligation increased repolarization heterogeneity. However, fetal
      cardiomyocyte engraftment in an infarcted region did not further increase
      repolarization heterogeneity.

PMID- 17543789
TI  - Left anterior descending coronary artery bridge: contraindication to cardiac
      transplantation?
AB  - We report two cases of cardiac transplantation of donor hearts with left anterior
      descending (LAD) myocardial bridging (MB). In the first case, the diagnosis was
      done only days after transplant. In the second case, a pre-operative angiography
      showed evidence of LAD myocardial bridging and the organ was used for a marginal
      recipient. Both patients tolerated the procedure very well and did not have peri
      operative cardiac complications. In this study, MB is discussed and its
      relationship to rejection of donor hearts is evaluated. In light of the growing
      demand for donated hearts, and in consideration of the relatively high and often
      undiagnosed occurrence of MB, a liberalized approach to acceptance of this
      anatomic variant could be adopted in the selection of donor hearts.
      Identification of MB in the prospective donor heart should not be an absolute
      contraindication for transplantation.

PMID- 17543790
TI  - Malignant arrhythmias secondary to a cardiac fibroma requiring transplantation in
      a teenager.
AB  - We report a case of a 13-year old girl with a diagnosis of cardiac fibroma who
      was followed for a decade. Although she was predominantly asymptomatic over this
      time period, she eventually developed significant ventricular arrhythmias. The
      arrhythmias were originally treated with anti-arrhythmic medications along with
      an automatic internal cardioverter-defibrillator. However, a nearly fatal event
      prompted a cardiac transplantation. This represents a unique case of a patient
      with cardiac fibroma who was bridged to transplantation with an internal
      cardioverter-defibrillator.

PMID- 17543791
TI  - Hyperacute rejection after lung transplantation caused by undetected low-titer
      anti-HLA antibodies.
AB  - Hyperacute rejection is an early complication of transplantation, caused by the
      presence in the recipient of pre-formed donor-directed antibodies (Ab). We report
      a case of fatal early graft dysfunction after lung transplantation in a female
      recipient with no anti-HLA Ab detected before transplantation. Further
      immunologic studies revealed the presence, in the pre-transplant serum, of low
      titer anti-HLA Ab directed against the donor's HLA, detectable only by flow
      cytometry screening for panel-reactive antibodies. This observation emphasizes
      the importance of sensitive Ab detection in patients awaiting lung
      transplantation. Women should be specifically targeted for such sensitive Ab
      detection.

PMID- 17543792
TI  - Urgent pump exchange for stroke resulting from a distorted HeartMate XVE inflow
      conduit.
AB  - Long-term left ventricular assist device (LVAD) implantation is associated with
      an inherent risk of transient ischemic attacks (TIAs). When TIAs occur in
      patients who have undergone placement of a HeartMate XVE LVAD, the pump must be
      assumed to be the likely source of the TIA. The HeartMate XVE is unique in that
      it has a pumping surface of flocked Biomer and a pump housing and inlet cannula
      coated with sintered titanium. This design facilitates coating of the surfaces
      with the patient's own cells, usually within 48 hours of implantation,
      effectively eliminating the pumping surface as a source of thromboemboli.
      Similarly, neither the outflow conduit nor the porcine outflow valve have been
      shown to be sources of thromboemboli, as they are both subjected to the wash-out
      of pulsatile systolic pressure. In our experience, the only components vulnerable
      to pannus formation are the inflow conduit and its associated valve, and then
      only when the inflow conduit is distorted at implantation. We describe an
      illustrative case of a patient supported with a HeartMate XVE LVAD who suffered a
      device-related stroke that was attributed to the inflow conduit, which was
      distorted during implantation to configure the pump for the patient's narrow body
      habitus. The resultant disruption in laminar flow was the most likely cause of
      the TIAs and stroke. Therefore, documented TIAs in patients with an implanted
      HeartMate XVE are an indication for urgent pump replacement, even if pump
      performance is otherwise normal. In this case, the pump was exchanged for a
      smaller, continuous-flow HeartMate II LVAD.

PMID- 17543793
TI  - Trichilemmal carcinoma of the skin mimicking a keloid in a heart transplant
      recipient.
AB  - Trichilemmal carcinoma is a rare cutaneous adnexal malignant tumor deriving from
      the outer root sheath of hair follicles. It is only rarely reported in recipients
      of solid (renal) organ transplants. We describe the first case of trichilemmal
      carcinoma presenting with a misleading clinical aspect in a heart transplant
      recipient. We then briefly outline the salient clinicopathologic features of this
      malignancy.

PMID- 17543794
TI  - Sirolimus-induced alveolar hemorrhage.
AB  - Sirolimus is a well-known, potent immunosuppressant that is widely used in solid
      organ transplantation, but it is not without potential side effects. A rare but
      devastating adverse effect is sirolimus-associated pulmonary toxicity. We report
      a case of sirolimus-induced diffuse alveolar hemorrhage confirmed by
      bronchoscopic findings (after other possible etiologies were ruled out) and by
      clinical and radiographic resolution of the pulmonary signs and symptoms a few
      days after sirolimus administration was stopped. This case and the existing
      literature on this topic suggest that sirolimus-induced pulmonary toxicity should
      be suspected in any patient taking immunosuppressants and who develops
      unexplained pulmonary symptoms.

PMID- 17543795
TI  - Early pediatric anthracycline cardiotoxicity: managed by serial heart and bone
      marrow transplantation.
AB  - We report a favorable outcome in a child who underwent cardiac transplantation
      for severe early post-anthracycline-induced cardiomyopathy, 9 months after
      completion of treatment for acute myeloid leukemia (AML). The child suffered a
      relapse of AML 2 months after cardiac transplantation and then underwent a
      successful bone marrow transplant. This case is unique in the literature. We
      believe it offers an alternative strategy for children with hematologic
      malignancies, where severe early post-anthracycline cardiotoxicity might preclude
      bone marrow transplantation.

PMID- 17543796
TI  - Possible everolimus-induced, severe, reversible encephalopathy after cardiac
      transplantation.
AB  - Neurotoxicity is a common adverse effect of cyclosporine (CsA) in transplant
      recipients. Although most patients develop mild toxic manifestations,
      leukoencephalopathy with seizures, visual complications, psychiatric symptoms and
      motor and speech disorders may occur. Whether everolimus exacerbates the
      neurotoxicity of CsA is not known. We describe a patient who developed severe
      neurologic complications, consistent with CsA-induced neurotoxicity, developing
      7.5 years after cardiac transplantation, 3 months after everolimus was added to
      the immunosuppressive regimen.

PMID- 17543797
TI  - A simplified technique for heart transplantation in mice: modified venous
      anastomosis.

PMID- 17543798
TI  - Is the current multiple-organ retrieval protocol detrimental to the heart?

PMID- 17543799
TI  - Orthopaedics: a wide range of patient care.

PMID- 17543800
TI  - Diversity in practice.

PMID- 17543801
TI  - Orthopaedic postoperative pain management.
AB  - Severe postoperative pain is common following orthopaedic surgery, and its safe
      and effective management can be challenging for everyone on the health care team.
      There are a variety of methods used to address orthopaedic postoperative pain and
      all incorporate the principles of multimodal analgesia. The purpose of this
      article is to provide an overview of the primary methods used to manage
      orthopaedic pain and describe the perianesthesia nurse's role in the
      administration of them.

PMID- 17543802
TI  - Osteoporosis: a national public health priority.
AB  - Osteoporosis, the most common bone disease, is a silent condition that affects
      millions of Americans. Fractures in individuals over the age of 50 can be the
      first sign of weak bones from osteoporosis. Many osteoporotic fractures can be
      prevented and treated. Healthy lifestyle choices such as proper diet, exercise,
      and medications can help prevent further bone loss and reduce the risk of
      fractures. Perianesthesia nurses have numerous opportunities to promote healthy
      behaviors for patients, family members, and themselves.

PMID- 17543803
TI  - Care of the orthopaedic trauma patient.
AB  - The perianesthesia nursing care of the orthopaedic trauma patient focuses on
      injuries of the musculoskeletal system and the associated muscles, ligaments,
      tendons, and joints. Multitrauma patients often sustain more than one
      musculoskeletal injury at the time of the traumatic event. Early stabilization,
      astute nursing assessments, and interventions are imperative to the patient's
      functional outcome and rehabilitation. Knowing the mechanism of injury is
      essential to understanding and caring for musculoskeletal trauma injuries.
      Because patients with traumatic orthopaedic injuries are at a higher risk for
      wound infections, it is important for perianesthesia nurses to initiate careful
      infection control practices. Recognizing significant orthopaedic trauma
      complications that include compartment syndrome, fat embolism syndrome, and
      hypovolemic shock is vital for saving the life or limb of the patient.

PMID- 17543804
TI  - A multidisciplinary approach to total joint replacement.
AB  - A multidisciplinary team was formed to look at consolidating and improving
      patient education for patients preparing to undergo total knee replacement or
      total hip replacement. The objective was to encompass disciplines from across the
      continuum of care, beginning with the surgeon's office through postdischarge
      rehabilitation. Project goals for the team were to develop the "ideal" pre and
      postoperative orders for total joint patients, review and revise current clinical
      and patient pathways for the total knee replacement patient and the total hip
      replacement patient, add rehabilitation services to clinical pathways, and
      develop a patient education class and patient education booklet. This article
      describes how working together with all disciplines involved resulted in a
      consolidated order set, clinical and patient pathways that reflected actual care
      and processes, a user-friendly patient education book, and a multidisciplinary
      patient education class. The end products led to consistency in the quality of
      care across the continuum from preadmission through postdischarge rehabilitation
      for total joint replacement patients.

PMID- 17543805
TI  - Care of the orthopaedic patient in the ambulatory surgery setting.
AB  - Orthopaedic surgical patients have specific needs based on the type of procedure,
      the anesthetic used, and the patient's individual social, physical, and emotional
      considerations. Although a procedure may be less extensive when the patient is
      discharged on the day of the procedure compared with an inpatient, the issues of
      mobility, activity level, medical equipment use, and potential complications are
      all considerations. This article provides insights about issues that nurses must
      address for orthopaedic and podiatric patients within the context of the
      ambulatory surgical experience.

PMID- 17543806
TI  - Continuous quality improvement: focus on orthopaedic excellence.

PMID- 17543807
TI  - Bed management displays to optimize patient flow from the OR to the PACU.

PMID- 17543808
TI  - Health literacy and its influence on patient safety.

PMID- 17543809
TI  - The matter of an "A".

PMID- 17543810
TI  - Conflicting results in clinical research: is the proof in the P value, the study
      design, or the pudding?

PMID- 17543811
TI  - "Going fishing"--the practice of reporting secondary outcomes as separate
      studies.

PMID- 17543812
TI  - Rebound pain scores as a function of femoral nerve block duration after anterior
      cruciate ligament reconstruction: retrospective analysis of a prospective,
      randomized clinical trial.
AB  - BACKGROUND AND OBJECTIVES: Continuous perineural femoral analgesia has been
      reported to reduce numeric rating pain scores (NRS, scale 0-10) after anterior
      cruciate ligament reconstruction (ACLR). In the current study, we determined
      rebound pain scores in autograft ACLR outpatients after nerve block analgesia
      resolved. METHODS: After standardized spinal anesthesia and perioperative
      multimodal analgesia, patients received a femoral perineural catheter and 50
      hours of saline or levobupivacaine. All patients received levobupivacaine (30 mL
      of 0.25% as a bolus) before the infusion. Patients completed a pain diary for 6
      days, indicating serial NRS scores and perceptions of when nerve block analgesia
      resolved. Block duration and rebound pain scores were computed. RESULTS: Data
      from 84 participants' pain diaries were analyzed. Patients receiving saline
      infusion reported mean nerve block duration of 37 hours versus 59 hours for
      patients receiving the levobupivacaine infusion (P < .001). Mean rebound pain
      scores increased by 2.0 (95% confidence interval, 1.6-2.4). Based on the
      computations used to derive block duration and rebound pain scores, each hour of
      additional block duration was predictive of a 0.03-unit reduction in rebound pain
      scores. CONCLUSIONS: In an anesthesia care protocol consisting of spinal
      anesthesia and multimodal analgesia during and after autograft ACL
      reconstruction, approximately 33 hours of additional nerve block duration were
      required to reduce rebound pain scores by one unit. Further study is required to
      determine rebound pain score differences when other local anesthetics and
      anesthetic/analgesic plans are being used and when other surgeries are being
      performed.

PMID- 17543813
TI  - Nausea, vomiting, sleep, and restfulness upon discharge home after outpatient
      anterior cruciate ligament reconstruction with regional anesthesia and multimodal
      analgesia/antiemesis.
AB  - BACKGROUND AND OBJECTIVES: We analyzed discharge outcome data after anterior
      cruciate ligament reconstruction (ACLR) under spinal anesthesia including a
      perineural femoral catheter and multimodal analgesia/antiemesis. The outcomes
      specifically addressed in this report are nausea, vomiting, and retching (NVR)
      and quality of sleep/difficulty falling asleep/daytime restfulness. METHODS: ACLR
      patients were randomized to saline or 0.25% levobupivacaine as a bolus and/or 50
      hour infusion. Patients completed the Quality of Recovery 40-item (QoR-40) survey
      on postoperative days 1 to 4. We analyzed predictors of perfect responses (i.e.,
      no NVR and perfect sleep-restfulness) by pooling these specific QoR-40 items.
      Prospectively collected QoR-40 data were analyzed retrospectively. RESULTS: Data
      from 233 participants were analyzed. The addition of the femoral nerve block or
      perineural catheter did not predict associated improvements in NVR or sleep
      restfulness. Previous days' NVR was the most consistent predictor of subsequent
      NVR, whereas gender and opioid consumption were less consistent predictors.
      Smoking status was not predictive of NVR. Previous days' sleep-restfulness was a
      consistent predictor of subsequent sleep-restfulness, whereas the presence of any
      moderate pain was a less consistent predictor of sleep-restfulness. CONCLUSIONS:
      NVR and quality of sleep-restfulness after the described regional anesthetic with
      multimodal analgesia and antiemesis is reported. Smoking status was not a
      predictor of NVR, and gender and opioid consumption were not consistently
      predictive of NVR. The addition of a femoral nerve block to the described
      multimodal technique was not associated with NVR or quality of sleep-restfulness.

PMID- 17543814
TI  - Comparison of different injectate volumes for stellate ganglion block: an
      anatomic and radiologic study.
AB  - BACKGROUND: Volumes from 5 to 20 mL of local anesthetic are used for stellate
      ganglion block. The variation of practice gave us the impetus to investigate the
      distribution of 3 different volumes of solution. We documented the regions
      reached by each volume to assess the possibility to reduce the injectate to 5 mL.
      MATERIALS AND METHOD: A total of 42 cadavers (84 halves), fixed by Thiel's method
      and on which pulse simulation was performed, were investigated. Of these 84
      halves, 28 were injected with 5 mL of contrast (group A), 28 halves with 10 mL
      (group B), and 28 halves with 20 mL (group C), according to the tissue
      displacement method. Immediately after injection, the cadavers were investigated
      by use of CT scans with a possible 3-dimensional reconstruction. In addition, 4
      halves of group A and group B were dissected, and the contrast distribution was
      determined by photography. RESULTS: Group A showed a constant dissemination from
      C4 to Th2-Th3, without spreading to ventral or lateral regions. In group B, a
      persistent spread from C4 to Th3 was documented. Ventral and lateral regions were
      also reached in one third of the specimens. Group C showed a constant
      dissemination from C3 to Th4-Th5, with additional spread to ventral, lateral, and
      posterior regions of the neck similar to that in group B. CONCLUSION: The use of
      5 mL results in an almost ideal vertical distribution in most of the cadavers,
      whereas high volumes--20 mL more so than 10 mL--are at risk of spreading
      extensively in both the vertical direction and also uncontrollably to other
      regions of the neck.

PMID- 17543815
TI  - Chronic intrathecal infusion of minocycline prevents the development of spinal
      nerve ligation-induced pain in rats.
AB  - BACKGROUND AND OBJECTIVES: Minocycline is a second-generation tetracycline with
      multiple biological effects, including inhibition of microglial activation.
      Recently, microglial activation has been implicated in the development of nerve
      injury-induced neuropathic pain. In this study, the authors examined the effects
      of continuous intrathecal minocycline on the development of neuropathic pain and
      microglial activation induced by L5/6 spinal-nerve ligation in rats. METHODS:
      Under isoflurane anesthesia, male Sprague-Dawley rats (200-250 g) received right
      L5/6 spinal-nerve ligation and intrathecal catheters connected to an infusion
      pump. Intrathecal saline or minocycline (2 and 6 microg/h) was given continuously
      after surgery for 7 days (n = 8 per group). The rat right hind paw withdrawal
      threshold to von Frey filament stimuli and withdrawal latency to radiant heat
      were determined before surgery and on days 1 to 7 after surgery. Spinal
      microglial activation was evaluated with OX-42 immunoreactivity on day 7 after
      surgery. RESULTS: Spinal-nerve ligation induced mechanical allodynia and thermal
      hyperalgesia on the affected hind paw of saline-treated rats. Intrathecal
      minocycline (2 and 6 microg/h) prevented the development of mechanical allodynia
      and thermal hyperalgesia induced by nerve ligation. It also inhibited nerve
      ligation-induced microglial activation, as evidenced by decreased OX-42 staining.
      No obvious histopathologic change was noted after intrathecal minocycline (6
      microg/h) infusion. CONCLUSIONS: In this study, the authors demonstrate the
      preventive effect of continuous intrathecal minocycline on the development of
      nociceptive behaviors induced by L5/6 spinal-nerve ligation in rats. Further
      studies are required to examine if continuous intrathecal minocycline could be
      used safely in the clinical setting.

PMID- 17543816
TI  - Ultrasound anatomy of the radial nerve in the distal upper arm.
AB  - BACKGROUND AND OBJECTIVES: We aimed to describe the ultrasound appearance of the
      radial nerve in the lateral aspect of the distal upper arm. This procedure was
      done to identify potential novel sites for ultrasound-guided radial-nerve block.
      METHODS: We scanned the lateral aspect of the distal upper arm in both arms of 50
      healthy adult volunteers (equal gender distribution), using a 38 mm, 5 to 10 MHz,
      linear ultrasound probe (SonoSite MicroMaxx, Hitchen, UK). Three points were
      defined: A, midway between the anterior process of the acromion and lateral
      epicondyle of the humerus; B, one third of the distance between A and the lateral
      epicondyle; C, two thirds of the distance between A and the lateral epicondyle.
      Subjects' arms were scanned between A and C. We measured the maximal transverse
      (parallel to skin) and anteroposterior (perpendicular to skin) diameters of the
      radial nerve and calculated its cross-sectional area. Depth of the radial nerve
      from the skin surface was measured, and its shape and appearance were noted.
      RESULTS: At point B, the radial nerve lay in the spiral groove of the humerus,
      closely associated with the profunda brachii artery and vein. At point C, the
      nerve had passed through the lateral intermuscular septum and lay between
      brachioradialis and brachialis muscles. In 99% of arms, the radial nerve was not
      visible at point A, but became visible between points A and B in 93% of arms. The
      depth at point B was significantly less than at point C (mean +/- SD: 1.21 +/-
      0.35 vs. 1.71 +/- 0.35 cm; P < .001). The measured depth of the nerve was
      positively correlated (P < .001) with body mass index and with arm circumference,
      but not with gender. The radial nerve was oval-shaped at both sites, with a cross
      sectional area of 3.1 +/- 0.7 mm(2) at point B and 2.9 +/- 0.7 mm(2) at point C.
      CONCLUSIONS: Points B and C may represent convenient, novel sites for ultrasound
      guided radial-nerve block. The nerve is clearly visualized and has not yet
      divided into superficial and deep branches. Point C may be the optimal site for
      radial-nerve block because of the smaller risk of vessel puncture. Our
      observations also demonstrate the ability of ultrasound to identify nerves at
      sites not clearly defined by surface anatomic landmarks.

PMID- 17543817
TI  - Ultrasound-guided obturator nerve block: a preliminary report of a case series.
AB  - BACKGROUND AND OBJECTIVES: Obturator-nerve block improves analgesia for knee
      surgery. Traditional techniques rely on surface landmarks, which can be variable
      and result in excessive performance times and multiple needle passes. The
      objective of this study was to evaluate a novel ultrasound-guided technique for
      localizing the obturator nerve. METHODS: A total of 22 patients undergoing
      anterior cruciate ligament repair had ultrasound-guided obturator-nerve blocks.
      Needles were directed under real-time ultrasound guidance. Endpoint for injection
      consisted of identifying contact of the tip of an insulated needle to nerve
      confirmed by adductor muscles' contraction. Local anesthetic was injected, and
      block was evaluated within 30 minutes. After that, ultrasound-guided sciatic
      femoral blocks were placed for surgical purposes. Data collected included: time
      required for nerve identification, minimum stimulating current, number of
      attempts for correct identification, preblock and postblock adductor muscles'
      strength, sensory-nerve block, and quality of surgical anesthesia. RESULTS: In
      91% of cases, the obturator nerve was correctly identified on first attempt
      within 30 +/- 23 seconds, as a hyperechoic flat or lip-shaped structure with
      internal hypoechoic dots. Minimal intensity of current to nerve stimulation was
      0.30 +/- 0.08 mA. All patients exhibited decreases in adductor strength. Sensory
      territories were variable, with no cutaneous distribution in 32% of the patients.
      Small-dose opioid supplementation was required in 14% of the patients, but none
      required general anesthesia to complete surgery. CONCLUSIONS: These preliminary
      data suggest that ultrasound-guided obturator-nerve identification and block are
      technically easy and highly successful.

PMID- 17543818
TI  - A randomized controlled trial of the anticatabolic effect of epidural analgesia
      and hypocaloric glucose.
AB  - BACKGROUND AND OBJECTIVES: The goal of the present study was to investigate
      whether epidural analgesia exerts a protein-sparing effect after colorectal
      surgery in the presence of hypocaloric glucose supply initiated with surgical
      skin incision. METHODS: We randomly allocated 10 patients to receive general
      anesthesia combined with epidural anesthesia with bupivacaine, followed by
      epidural analgesia using bupivacaine/fentanyl, and 10 patients to receive general
      anesthesia, followed by patient-controlled analgesia with intravenous morphine.
      All patients received a 48-hour infusion of glucose 10% from surgical skin
      incision until the second day after surgery. The glucose infusion rate provided
      50% of the patient's resting energy expenditure. Kinetics of protein and glucose
      metabolism were assessed by a stable-isotope tracer technique (L-[1-(13)C]leucine
      and [6,6-(2)H(2)]glucose). RESULTS: The rate of appearance of leucine increased
      in the intravenous-analgesia group (112 +/- 29 to 130 +/- 25 micromol/kg/h) 2
      days after surgery, and this increase was more pronounced than in the epidural
      analgesia group (preoperative 120 +/- 24, postoperative 123 +/- 22 micromol/kg/h,
      P < .05). Leucine oxidation rate increased in the intravenous analgesia group
      from 17 +/- 8 to 23 +/- 8 micromol/kg/h and in the epidural group from 17 +/- 6
      to 19 +/- 7 micromol/kg/h without the difference between the groups reaching
      statistical significance (P = .067). Nonoxidative leucine disposal remained
      unaltered in both groups. No differences in glucose metabolism were seen between
      the groups. CONCLUSIONS: Epidural analgesia inhibits the increase in whole-body
      protein breakdown in patients receiving perioperative hypocaloric glucose
      infusion initiated with surgical skin incision. However, oxidative protein loss,
      protein synthesis, and glucose metabolism are not affected by epidural analgesia.

PMID- 17543819
TI  - Altered blood flow in terminal vessels after local application of ropivacaine and
      prilocaine.
AB  - BACKGROUND: Ropivacaine is primarily a local anesthetic, but it also acts as a
      vasoactive agent. Case reports have described a critical reduction in blood flow
      when higher concentrations of ropivacaine were used for peripheral-nerve blocks.
      One hypothesis is that local application of ropivacaine in tissues supplied by
      end arteries reduces tissue blood flow because of arterial vasoconstriction.
      METHODS: Rats were anesthetized by inhalation of isoflurane. The tail vessels
      were carefully dissected from the ventral side near the radix. Randomly, normal
      saline, prilocaine 0.5%, prilocaine 0.5% with epinephrine 1:200,000, ropivacaine
      0.2%, ropivacaine 0.5%, or ropivacaine 0.75% was applied directly to the artery.
      Blood flow in the tail was continuously measured by use of laser Doppler
      flowmetry distal to the surgical site. Changes in temperature in the tail were
      detected by use of infrared thermography. RESULTS: Blood flow decreased after the
      application of ropivacaine at all concentrations in comparison with normal saline
      (P < .01 at t = 10 minutes, P < .001 at t = 20, 30, and 40 minutes). This effect
      was most pronounced at t = 30 minutes for ropivacaine 0.5% (with a 64.5% decrease
      in blood flow). Prilocaine 0.5% with epinephrine 1:200,000 reduced blood flow by
      up to 44.7% (t = 20 minutes, P < .001). In comparison with the placebo, the
      application of ropivacaine 0.5% and 0.75%, as well as prilocaine 0.5% with
      epinephrine 1:200,000, caused a significant reduction in tail temperature (P <
      .001 at t = 20, 30, and 40 minutes). No alteration in blood flow or temperature
      was seen after application of prilocaine 0.5%. CONCLUSIONS: The application of
      ropivacaine directly to a rat's tail artery diminished blood flow and lowered
      regional skin temperature. These effects were dose related. The use of
      ropivacaine at higher concentrations can, therefore, not be recommended if
      tissues supplied by end arteries might be affected.

PMID- 17543820
TI  - Howard Fields, M.D.: Bonica lecturer.

PMID- 17543821
TI  - Understanding how opioids contribute to reward and analgesia.
AB  - Opioids acting at the mu opioid (MOP) receptor produce powerful analgesia. They
      also produce an intensely rewarding effect that can lead to addiction. The
      analgesic effect of MOP receptor agonists derives from a direct inhibitory effect
      on pain transmission at the spinal-cord level and through activation of a
      descending pain-modulatory pathway. The rewarding effect of MOP agonists is the
      result of their actions in the mesostriatal dopamine pathway classically
      associated with both natural and drug rewards. Both the analgesic and rewarding
      effect of MOP agonists are best understood in the context of decision making
      under conditions of conflict. Pain is one of many competing motivational states,
      and endogenous opioids suppress responses to noxious stimuli in the presence of
      conflicting motivations, such as hunger or a threatening predator. When a food
      reward is available, MOP agonists microinjected into the mesostriatal circuit
      promote its consumption, while concomitantly suppressing responses to noxious
      stimulation. The mesostriatal "reward" circuit, thus, appears to perform a
      function critical to decision making and can either amplify or suppress responses
      to noxious stimuli.

PMID- 17543822
TI  - High-resolution ultrasound-guided high interscalene plexus block for carotid
      endarterectomy.
AB  - BACKGROUND AND OBJECTIVES: High-resolution ultrasound imaging (HRUI) allows real
      time visualization of peripheral nerves, needle insertion, and the spread of
      local-anesthetic (LA) solution. We evaluated the feasibility of performing a high
      interscalene brachial-plexus block for carotid endarterectomy by means of HRUI,
      thereby limiting the amount of LA to the dose required to sufficiently surround
      the relevant nerve structures. METHODS: The interscalene brachial plexus was
      localized in the interscalene groove at its most cephalad point in 14 patients
      undergoing carotid endarterectomy by use of an ultrasound device with a 17.5 MHz
      transducer. Up to 20 mL of ropivacaine 0.5% was injected. RESULTS: In all
      patients, HRUI allowed clear delineation of the upper part of the interscalene
      brachial plexus at the level of the 4th cervical vertebra appearing as 1
      hypoechoic, roundish, hypodense node located in a distance of 1.5 +/- 0.3 cm to
      the skin, 1.5 +/- 0.2 cm lateral to the common carotid artery, and 0.6 +/- 0.2 cm
      from the transverse process of the spine. Likewise HRUI allowed a clear
      delineation of minor blood vessels and adjacent anatomic structures, as well as
      accurate placement of the needle close to the nerves. Real-time observation of LA
      spread during injection was possible, even in increments of less than 1 mL.
      CONCLUSIONS: High-resolution ultrasonic imaging allows clear depiction of the
      target tissues and facilitates accurate needle placement during high interscalene
      brachial-plexus blocks. This technique may minimize the risk of direct puncture
      related complications, as well as accidental intravascular injection of LA. The
      observation of LA spread in all patients, even in small increments of less than 1
      mL might enhance safety by limiting the injected LA to the actual demand. Well
      placed LA spread could potentially avoid central nervous toxicity caused by
      intravascular injection or resorption of inadequately high dosages, in particular
      in nerve blocks of the highly vascularized neck region.

PMID- 17543823
TI  - Ultrasound-guided and CT-navigation-assisted periradicular and facet joint
      injections in the lumbar and cervical spine: a new teaching tool to recognize the
      sonoanatomic pattern.
AB  - BACKGROUND AND OBJECTIVES: The aim of this study is to provide a teaching tool to
      facilitate the acquirement of periradicular and facet-joint infiltration
      techniques in the cervical and lumbar spine. METHODS: On 3 fresh cadavers, a
      computed tomography (CT) of the lumbar and cervical region was obtained. By use
      of a dedicated image navigation and reconstruction system, sonographic images
      were generated and fused with the collected CT data set. RESULTS: The sonoanatomy
      can be instantly compared with the correlating CT-images. This new bimodal method
      allows for simultaneous views of CT and ultrasound images. Multiplanar imaging of
      ultrasound-guided infiltrations is facilitated. CONCLUSIONS: This teaching tool
      provides immediate CT-verification of sonographically identified structures and
      helps in the identification of bony landmarks, which are necessary for facet
      joint and periradicular injections.

PMID- 17543824
TI  - Exploring origins: was John Bonica's model of modern-day pain management
      influenced by John Lundy's earlier work?
AB  - Contemporary pain medicine is a multimodality and multidisciplinary field. Many
      of the current ideas and styles of practice that influence the specialty today
      can be traced back to John Bonica, M.D., and his model of pain management
      introduced more than 50 years ago. Although much of the foundation that Bonica
      helped form involved several original concepts, historically, other
      anesthesiologists who were Bonica's predecessors also laid the groundwork for
      what the practice of pain medicine is today. In particular, Emery Rovenstine,
      M.D., and John Lundy, M.D., had early block clinics to treat painful conditions.
      While in the army during World War II, Bonica worked closely with his Chief of
      Surgery, Joel Deuterman, M.D., a physician who had trained at the Mayo Clinic,
      where he was exposed to Lundy and his techniques. Deuterman may have influenced
      Bonica's ideas concerning the treatment of chronic painful conditions.

PMID- 17543827
TI  - New approaches to ganglion impar blocks via coccygeal joints.

PMID- 17543828
TI  - Local opioid analgesia at cervical sympathetic ganglia: what is the contribution
      of placebo effect?

PMID- 17543829
TI  - Clonidine in resuscitation of bupivacaine-related cardiac arrest.

PMID- 17543830
TI  - Prolonged femoral nerve palsy after ilio-inguinal nerve block.

PMID- 17543832
TI  - Modification of the sitting position for posterior brachial plexus block by
      utilizing an eye surgery stretcher.

PMID- 17543833
TI  - Between the farm and the clinic: agriculture and reproductive technology in the
      twentieth century.

PMID- 17543834
TI  - Reflections on the reproductive sciences in agriculture in the UK and US, ca.
      1900-2000+.
AB  - This paper provides a brief comparative overview of the development of the
      reproductive sciences especially in agriculture in the UK and the US. It begins
      with the establishment by F. H. A. Marshall in 1910 of the boundaries that framed
      the reproductive sciences as distinct from genetics and embryology. It then
      examines how and where the reproductive sciences were taken up in agricultural
      research settings, focusing on the differential development of US and UK
      institutions. The reproductive sciences were also pursued in medical and
      biological settings, and I discuss how the intersections among all three allowed
      the circulation of both ideas and scientists' careers. Across the twentieth
      century, scientific leadership in the reproductive sciences alternated between
      the UK and US, and these patterns are elucidated. I conclude with thoughts on
      future research that might emphasize the elaboration of industrialization
      processes in agriculture and new capacities to transform both reproductive
      processes and their products--life itself--as biopower comes to be more
      ambitiously understood as extending across all species.

PMID- 17543835
TI  - The history of three scientific societies: the Society for the Study of Fertility
      (now the Society for Reproduction and Fertility) (Britain), the Societe Francaise
      pour l'Etude de la Fertilite, and the Society for the Study of Reproduction
      (USA).
AB  - Three scientific societies devoted to the study of reproduction were established
      in Britain, France and USA in the middle of the twentieth century by clinical,
      veterinary and agricultural scientists. The principal motivation for their
      establishment had been the study of sterility and fertility of people and
      livestock. There was also a wider perspective embracing other biologists
      interested in reproduction more generally. Knowledge disseminated through the
      societies' scientific meetings and publications would bear upon human and animal
      population problems as well as basic reproductive physiology and its
      applications. New journals dealing with reproductive physiology, having worldwide
      appeal, were established in Britain and USA. The financial resources of at least
      one of the societies and its journal are directed towards charitable functions,
      including financial support for travel to scientific meetings, for visits to
      particular laboratories, and for research in the short term, including that of
      undergraduates. Perhaps the example of the British society has given rise to
      others having a more specialised focus, as well as to the formation of the
      European Society for the Study of Human Reproduction and Embryology.

PMID- 17543836
TI  - 'Crook' pipettes: embryonic emigrations from agriculture to reproductive
      biomedicine.
AB  - While cloning, stem cells, and regenerative medicine are often imagined in a
      futurial idiom--as expectations, hype, hope and promises--this article approaches
      the remaking of genealogy in such contexts from a historical route. Through a
      series of somewhat disparate historical connections linking Australian sheep to
      the development of clinical IVF and the cloning of Dolly at the Roslin Institute
      in Scotland in 1996, this article explores the linkages through which
      agriculture, embryology, and reproductive biomedicine are thickly intertwined.
      Key to this examination is not only the history of experimental sheep breeding,
      and its somewhat unexpectedly genealogical connections to (Australian) national
      identity ('wool in the veins'), but also the re-emergence of a distinctive
      frontier ethos in the context of assisted conception, and later human embryonic
      stem cell derivation. I have set this scene of genealogical interconnection
      against the criss-crossing traffic between Britain and Australia, and the wool
      trade, to emphasise the importance of global, as well as local, connections in
      the bloodlines of animals such as Dolly. In sum, this article examines the idea
      of the 'biological frontier' by exploring its histories as a means to offset the
      assumption that this frequently encountered idiom describes a future that is, or
      must be, by definition, unknown and unknowable.

PMID- 17543837
TI  - Great expectations--German debates about artificial insemination in humans around
      1912.
AB  - In May 1912, reports on successful attempts at artificial insemination hit the
      German papers. Over the following months, the topic was taken up in medical
      lectures, in the debates of medical associations, and in medical journals. The
      technique--which had not much changed since the days of James Marion Sims-
      apparently triggered the imagination of scientists, medical doctors, journalists
      and authors. That artificial insemination met such interest, however, was not
      primarily due to its medical usefulness or proven success. Given that
      insemination with donor sperm was out of the question for most doctors and that
      ideas about the fertile period within the menstrual cycle were erroneous,
      contemporary attempts at insemination in humans hardly ever worked. Public
      interest in this topic rather reflects the desires and expectations which
      contemporaries associated with artificial insemination and with modern,
      scientific medicine. What appears to be a comparatively straight forward, low
      tech operation today was imagined as a way or creating life artificially. Thus
      the topic was able to mobilise fears and expectations. The debate not only
      reflected contemporary beliefs about the possibilities and dangers of modern
      medicine, it also addressed the meaning of reproduction and infertility and the
      future of gender relations.

PMID- 17543838
TI  - The return of the Inseminator: Eutelegenesis in past and contemporary
      reproductive ethics.
AB  - Eugenicists in the 1930s and 1940s emphasised our moral responsibilities to
      future generations and the importance of positively selecting traits that would
      benefit humanity. In 1935 Herbert Brewer recommended 'Eutelegenesis' (artificial
      insemination with sperm from specially selected males) so that that future
      generations are not only protected from hereditary disease but also become more
      intelligent and fraternal than us. The development of these techniques for human
      use and animal husbandry was the catalyst for the cross fertilization of moral
      ideas and the development of a critical procreative morality. While eugenicists
      argued for a new critical morality, religious critics argued against artificial
      insemination because of its potential to damage important moral institutions. The
      tension between critical and conservative procreative morality is a feature of
      the contemporary debates about reproductive technologies. This and some of the
      other aspects of the early and contemporary debates about artificial insemination
      and reproductive technologies are discussed in this article.

PMID- 17543839
TI  - From 'public service' to artificial insemination: animal breeding science and
      reproductive research in early twentieth-century Britain.
AB  - Artificial insemination (AI) was the first conceptive technology to be widely
      used in agriculture. Whereas at the beginning of the twentieth century all cows
      in England and Wales were mated to bulls, by the end of the 1950s 60% conceived
      through artificial insemination. By then a national network of 'cattle breeding
      centres' brought AI within the reach of every farmer. In this paper I explore how
      artificial insemination, which had few supporters in the 1920s and 1930s, was
      transformed into an 'indispensable' method for reproducing cattle. I discuss the
      factors that made organised AI possible (but still negotiable and controversial),
      including changes in cultures of cattle breeding, novel State involvement in
      bovine reproduction, the rise of new 'animal breeding research' centres at
      Cambridge, Edinburgh and Reading universities, war preparations and central
      planning by the Milk Marketing Board (from 1933). I go on to show that the
      unprecedented focus on bovine reproduction set in motion by the AI centres
      effectively generated new networks of reproductive research, through these the
      'biopower' of the farm was incorporated into the clinic. The example of AI shows
      that by combining the history of reproductive technology in agriculture and
      medicine we can give a richer account of modern reproduction.

PMID- 17543840
TI  - Cutting across nature? The history of artificial insemination in pigs in the
      United Kingdom.
AB  - Artificial insemination (AI) has a considerable cultural significance in addition
      to its economic and technical impact. This study is the first to examine the
      history of its application to pigs, and uses evidence provided directly by both
      the scientists involved in its development, and some of the farmers who were
      among the first to use it, in addition to archival and published sources, to show
      how the scientific studies of the 1950s evolved into a widely available
      commercial product by the 1980s. It describes the initial scientific work and
      quantifies the extent to which the technique was used at various points in time,
      showing that by 1990 nearly one half of UK pig herds were using AI for more than
      25% of all services. It traces changes in the techniques employed and argues that
      these were the result of a multi-dimensional process of contemporaneous change.
      The various dimensions are identified firstly as authorities, meaning the people
      and organisations controlling the perception, administration, control, and so on,
      of the technique; secondly the discourses employed by the authorities; and
      thirdly the media by which the discourses were disseminated. Finally, it is
      suggested that this approach might be used more widely to examine the
      construction of other technologies.

PMID- 17543841
TI  - The farm as clinic: veterinary expertise and the transformation of dairy farming,
      1930-1950.
AB  - This paper explores the wartime creation of veterinary expertise in cattle
      breeding, and its contribution to the transition between two very different types
      of agriculture. During the interwar period, falling prices and steep competition
      from imports caused farmers to adopt a 'low input, low output' approach. To cut
      costs, they usually butchered, marketed or doctored diseased cows in preference
      to seeking veterinary aid. World War II forced a greater dependence on domestic
      food production, and inspired wide-ranging state-directed attempts to increase
      agricultural output. However, the weak connection between veterinary services and
      livestock productivity meant that the drive for greater milk yields did not
      automatically translate into a demand for improved veterinary health care. Rather
      veterinary expertise had to be actively created and made relevant to the new
      context. Leaders of the profession secured this goal through establishing a
      government-backed 'scheme for the control of certain diseases of dairy cows'.
      Drawing on pre-existing but rarely applied reproductive technologies, the scheme
      provided the opportunities and education necessary for more extensive veterinary
      interventions in cattle breeding. I show how its operation transformed
      understandings of fertility, raised veterinarians to the status of experts, won
      them the patronage of farmers and the state, and facilitated the shift to a
      productivity-oriented agriculture.

PMID- 17543842
TI  - Managing cows: an ethnography of breeding practices and uses of reproductive
      technology in contemporary dairy farming in Lombardy (Italy).
AB  - The aim of this article is to contribute detailed ethnographic material to
      broaden the scope of what we mean by reproductive technology. Technology can be
      defined not only by a series of laboratory techniques (such as artificial
      insemination and embryo transfer) that are drafted into the daily management of
      the animal body, but also by a range of on-farm management strategies and working
      routines, as well as the cultural dispositions, social networks and tacit
      knowledge of the actors involved. RT is communicated to lay operators and
      disseminated amongst semi-professional figures such as breed experts, herd
      inspectors and technical consultants. The practical contexts in which
      reproductive knowledge is popularized and applied provide ample scope for local
      negotiations, resistance and conflict. Professional knowledge about breed
      improvement is personalised and appropriated by operators and plays a role in
      power relations and the exercise of personal charisma as well as being specific
      to context, in particular the nuances of pre-existing relationships of trust,
      friendship, kinship or hierarchy. No wonder then that many ambivalences and
      compromises coexist in the practice of applying 'reproductive knowledge' to breed
      selection.

PMID- 17543843
TI  - The work of the Animal Research Station, Cambridge.
AB  - This paper traces the history of the Animal Research Station, Cambridge from its
      establishment in 1932 to its closure in 1986. The author worked there for forty
      years and was Director from 1979. Originally set up as a field station for
      Cambridge University's School of Agriculture, the Station was expanded after
      World War II as the Agricultural Research Council's Unit of Animal Reproduction.
      Beginning with semen and artificial insemination, research at the Station soon
      embraced superovulation and embryo transfer in farm animals. Many other
      technologies were also developed here, including IVF in pigs, cloning by nuclear
      transplantation of early embryonic cells, and the first genetically modified farm
      animals in Britain. This account recalls the Directors of the Station and their
      research teams together with details of their pioneering contribution to
      reproductive biology.

PMID- 17543844
TI  - The farm and the clinic: an inquiry into the making of our biotechnological
      modernity.

PMID- 17543845
TI  - Male midwives are OK.

PMID- 17543846
TI  - The role of acetaldehyde in upper digestive tract cancer in alcoholics.
AB  - Chronic excessive alcohol consumption is the strongest risk factor for upper
      aerodigestive tract (UADT) cancer. Multiple mechanisms are involved in alcohol
      associated cancer development of the UADT, including acetaldehyde (AA) effects.
      AA is toxic, mutagenic, and carcinogenic. Evidence of the role of AA in alcohol
      associated carcinogenesis derived from genetic linkage studies in alcoholics.
      Polymorphism or mutation in genes coding for AA generation or detoxification
      enzymes are associated with increased cancer risk. It has been clearly shown in
      Asians that individuals carrying the acetaldehyde dehydrogenase 2*2 (ALDH2*2)
      allele have a significantly increased cancer risk when they consume alcohol. In
      Caucasians, alcohol dehydrogenase 1*1 (ADH1C*1) allele encodes for an alcohol
      dehydrogenase (ADH) isoenzyme, which produces 2.5 times more AA than the
      corresponding allele ADH1C*2. The authors found that the ADH1C*1 allele frequency
      and rate of homozygosity was significantly associated with an increased risk for
      alcohol-related cancer. AA seems to be an important factor in alcohol-associated
      carcinogenesis of the UADT.

PMID- 17543847
TI  - Measurement of extra-pancreatic secretory function by 13C-dipeptide breath test.
AB  - A simple breath test was developed for assessment of exocrine pancreatic function
      employing 13C-dipeptide [ie, benzoyl-L-tyrosyl-[1-(13)C]alanine (Bz-Tyr-Ala)],
      and this test was examined to determine whether it can be used to diagnose
      exocrine pancreatic insufficiency in patients with chronic pancreatitis. The
      subjects, 24 patients with chronic pancreatitis and 16 healthy adult controls,
      underwent the Bz-Tyr-Ala breath test, in which breath samples were collected
      every 10 min up to 90 min after oral administration of an aqueous solution of 5
      mg/kg Bz-Tyr-Ala (7 mM). They also underwent a breath test with [1-(13)C]alanine
      equimolar to that contained in Bz-Tyr-Ala and the N-benzoyl-L-tyrosyl-p
      aminobenzoic acid (BT-PABA) test. Delta13CO2 values at 10-60 min for the Bz-Tyr
      Ala breath test were significantly lower in chronic pancreatitis patients than in
      normal controls. However, the [1-(13)C]alanine breath test results did not differ
      between patients and normal controls. The correlation coefficient between the Bz
      Tyr-Ala breath test Delta13CO2 value at 20 min, and the results of the BT-PABA
      test were r=0.726 (r2=0.527, P<0.0001). The results suggest that this newly
      developed Bz-Tyr-Ala breath test can quickly and noninvasively diagnose the
      exocrine pancreatic dysfunction.

PMID- 17543848
TI  - Peritoneal effects of intravenous iron sucrose administration in rats.
AB  - Intravenous iron supplementation is commonly used in uremic patients treated with
      peritoneal dialysis. Infusion of iron compounds results in various systemic
      noxious effects, mainly because of its prooxidant and proinflammatory actions.
      The authors studied how the intravenous infusion of iron sucrose (IS) affects
      intraperitoneal homeostasis in rats undergoing acute peritoneal dialysis.
      Experiments were performed on Wistar rats, which were infused intravenously with
      IS in a dose 10 mg/kg body weight or with normal saline in the controls.
      Simultaneously, 4-hour acute peritoneal dialysis was started. At the end of the
      dialysis, systemic and peritoneal inflammatory reaction and peritoneal
      permeability were evaluated. Compared with controls, rats exposed to IS showed
      increased dialysate iron concentration by +70%, P<0.001, and in the differential
      cell count, more eosinophils (+113%, P<0.05) and fewer macrophages (-16%, P<0.05)
      existed. In in vitro conditions, macrophages obtained from IS-treated rats
      released more tumor necrosis factor-alpha (TNF-alpha; +173%, P<0.05) upon
      stimulation with endotoxin. Additionally increased (+73%, P<0.01) dialysate
      elastase activity was found in IS-treated animals. Rats infused with IS
      demonstrated increased peritoneal permeability to total protein (+60%, P<0.001)
      as compared with control animals. When rats with simultaneous peritonitis
      received intravenous IS, ex vivo isolated peritoneal leukocytes generated more
      free radicals (+73%, P<0.05) than did cells harvested from control animals. It
      has been concluded that intravenous infusion of IS affects the intraperitoneal
      homeostasis in rats, moving it toward the inflammatory state. These changes may
      contribute to peritoneal damage.

PMID- 17543849
TI  - Cholesterol synthesis prevails over absorption in metabolic syndrome.
AB  - The objective of this study was to investigate cholesterol metabolism and its
      association with glucose metabolism and genetic regulation in metabolic syndrome.
      Overall, 74 subjects with clinically defined metabolic syndrome and sex and age
      matched controls (n=74) were recruited. Cholesterol metabolism was assayed with
      serum non-cholesterol sterols, surrogate markers of synthesis, and fractional
      absorption of cholesterol and was related to variables of glucose and insulin
      action and to the common polymorphisms of the ABCG5 and ABCG8 genes. Serum
      squalene and non-cholesterol sterols were analyzed with gas-liquid chromatography
      (GLC) and presented as ratios to cholesterol. Also, synthesis marker/absorption
      marker ratios were calculated. The subjects with metabolic syndrome had higher
      cholesterol synthesis marker ratios, including squalene, and lower absorption
      marker ratios than controls. When adjusted with body mass index (BMI) and waist
      circumference, differences in some of the absorption markers (plant sterols), but
      not in the synthesis markers, disappeared. Plasma glucose, serum triglycerides,
      and homeostasis model assessment (HOMA) index were positively associated with
      cholesterol synthesis/absorption marker ratios (r=0.264 to 0.353, P<0.05 for
      all). In multivariate analysis, the serum squalene ratio was the best variable of
      those of cholesterol metabolism explaining the presence of metabolic syndrome.
      The polymorphisms of ABCG5 and ABCG8 genes did not differ between the cases and
      controls. In conclusion, cholesterol synthesis prevails over absorption in
      metabolic syndrome. The high serum squalene ratio turned out to be associated
      with the prevalence of metabolic syndrome. The perturbations of cholesterol
      metabolism seem to be related to abdominal obesity, and weight reduction might
      normalize cholesterol metabolism.

PMID- 17543850
TI  - Adiponectin levels are associated with coronary artery disease across Caucasian
      and African-American ethnicity.
AB  - The hypothesis was tested that plasma levels of adiponectin would be associated
      with coronary artery disease (CAD) across African-American and Caucasian
      ethnicity and gender. Adiponectin levels, cardiovascular risk factors, and extent
      of CAD were measured in 453 subjects (173 African-American and 280 Caucasian men
      and women). The distribution of adiponectin levels differed significantly between
      African-Americans and Caucasians (P<0.0001). Among African-Americans, the
      adiponectin distribution was skewed toward lower levels. For women, adiponectin
      levels were higher among Caucasians compared with African-Americans (P<0.001),
      whereas no interethnic difference was observed for men. Irrespective of ethnic
      group, subjects with CAD had lower levels of adiponectin than did subjects
      without CAD. Adiponectin was negatively and significantly associated with waist
      hip ratio, body mass index, diastolic blood pressure, insulin level, and
      homeostasis model assessment-insulin resistance in both ethnic groups. Among
      lipid parameters, total cholesterol, triglyceride, and low-density lipoprotein
      cholesterol levels were negatively correlated with adiponectin, whereas the high
      density lipoprotein cholesterol level correlated positively for both African
      Americans and Caucasians. In a multiple regression model, controlling for gender,
      ethnicity, and other CAD risk factors, adiponectin levels were negatively
      associated with CAD (P<0.05). The results indicate that, across gender and
      ethnicity, low adiponectin levels may be an independent risk factor for CAD.

PMID- 17543851
TI  - Effect of ambient particulate matter exposure on hemostasis.
AB  - Epidemiological studies have linked levels of particulate matter (PM) in ambient
      air to cardiovascular mortality and hospitalizations for myocardial infarction
      (MI) and stroke. Thrombus formation plays a primary role in potentiating acute
      cardiovascular events, and this study was undertaken to determine whether
      pulmonary exposure to PM alters hemostasis. PM was collected from the Chapel
      Hill, NC airshed and was administered to mice by intratracheal instillation at a
      dose previously shown to exacerbate myocardial ischemia-reperfusion injury.
      Twenty-four hours after exposure, an increase occurred in the number of
      circulating platelets and plasma concentrations of fibrinogen and soluble P
      selectin. The concentration of tissue factor pathway inhibitor (TFPI) in plasma
      was decreased, whereas the plasma concentration of plasminogen activator
      inhibitor (PAI-1) was increased. Consistent with these observations, bleeding
      time from a tail-tip transection was shortened. These results provide evidence
      that PM exposure alters hemostasis in otherwise healthy animals and may thereby
      promote clot formation and impede clot resolution in susceptible individuals. The
      results also establish definite hemostatic endpoints that can be used to further
      investigate the effects of dose and particle characteristics on the toxicity of
      ambient particles.

PMID- 17543852
TI  - Toxicity and hemodynamic effects after single dose administration of MalPEG
      hemoglobin (MP4) in rhesus monkeys.
AB  - Maleimide-polyethylene glycol-modified (MalPEG) hemoglobin, 4.3 g/dL (MP4;
      Hemospan), is a hemoglobin-based oxygen carrier consisting of human hemoglobin
      (Hb) modified with maleimide polyethylene glycol. This study evaluates the
      potential toxicity and hemodynamic actions of a single dose of MP4 administered
      by exchange transfusion to rhesus monkeys. Monkeys were administered MP4 (21
      mL/kg, or approximately 30% of estimated blood volume) or an equivalent volume of
      lactated Ringer's solution (LR). In the toxicity study, blood samples were
      obtained predose and 3, 7, and 13 days after dosing for clinical chemistry and
      hematology. Animals were euthanized for complete necropsy and histopathology on
      day 3 or day 13. A separate group of animals was used for evaluation of arterial
      pressure, core temperature, and electrocardiogram, by telemetry, for 7 days after
      dosing with MP4. The results demonstrate no significant toxicity, with only
      modest, transient elevation of aspartate aminotransferase (AST), alanine
      aminotransferase (ALT), and lactate dehydrogenase (LDH) on day 3. Mild anemia
      caused by hemodilution was observed at each time point in both groups, but to a
      slightly greater degree in the MP4-treated animals. Histologic observations
      included foamy or vacuolated macrophages in the spleen and marrow of the sternum,
      rib, and femur, representing the accumulation of test article or a metabolite. In
      the telemetry study, no changes occurred in arterial pressure, heart rate, or
      electrocardiogram attributable to administration of MP4 at any time for 7 days
      after administration. These results demonstrate that MP4 is safe and is without
      hemodynamic effects when administered as an exchange transfusion of 30% of
      estimated blood volume.

PMID- 17543853
TI  - CLASPing microtubules at the trans-Golgi network.
AB  - Microtubule (MT) arrays can be formed either from centrosomes or from
      noncentrosomal locations. In this issue of Developmental Cell, Efimov and
      colleagues report a role of CLASPs, the MT plus end-binding proteins, in MT
      formation from Golgi, implicating Golgi-originated MT arrays in efficient cell
      migration (Efimov et al., 2007).

PMID- 17543854
TI  - Coordination of cell proliferation and differentiation: finding a GEM in the
      root?
AB  - How cells acquire specific fates in conjunction with cell division is a major
      developmental question. In a recent issue of Nature, Caro and colleagues describe
      the Arabidopsis protein GEM, which interacts both with DNA-replication and
      transcriptional regulators (Caro et al., 2007). The results are surprisingly
      reminiscent of the dual functions reported for Geminin in animals.

PMID- 17543855
TI  - A methylation rendezvous: reader meets writers.
AB  - It is well established that two marks of silent chromatin, DNA methylation and
      histone H3 methylation at lysine 9, engage in an epigenetic conversation. In a
      recent issue of Genes & Development, Smallwood et al. (2007) report that the
      mammalian HP1 adaptor "translates" methylation information from histone to DNA,
      helping to cement epigenetic expression states.

PMID- 17543856
TI  - Energy regulation: HIF MXIes it up with the C-MYC powerhouse.
AB  - The phenomenon of aerobic glycolysis observed in cancer cells has remained
      unexplained. In the May 2007 issue of Cancer Cell, Zhang and colleagues determine
      that the hypoxia-inducible factor family of transcriptional factors regulate
      mitochondrial biogenesis through inhibition of C-MYC.

PMID- 17543857
TI  - The mother-to-child transition.
AB  - Recent genome-scale analyses have uncovered the magnitude of the changes in mRNA
      populations that occur during the maternal-to-zygotic transition in early
      Drosophila embryos as well as two of the key regulators of this process, SMAUG
      and bicoid stability factor (BSF).

PMID- 17543858
TI  - The ins and outs of Arabidopsis embryogenesis.
AB  - In this issue of Developmental Cell, Nodine and colleagues show that two related
      leucine-rich repeat receptor kinases, RECEPTOR-LIKE PROTEIN KINASE1 and
      TOADSTOOL2, are critical in establishing radial pattern in the Arabidopsis embryo
      (Nodine et al., 2007). Embryos lacking these kinases show replacement of outer
      cell fates with inner cell fates.

PMID- 17543859
TI  - zucchini and squash encode two putative nucleases required for rasiRNA production
      in the Drosophila germline.
AB  - RNAi is a widespread mechanism by which organisms regulate gene expression and
      defend their genomes against viruses and transposable elements. Here we report
      the identification of Drosophila zucchini (zuc) and squash (squ), which function
      in germline RNAi processes. Zuc and Squ contain domains with homologies to
      nucleases. Mutant females are sterile and show dorsoventral patterning defects
      during oogenesis. In addition, Oskar protein is ectopically expressed in early
      oocytes, where it is normally silenced by RNAi mechanisms. Zuc and Squ localize
      to the perinuclear nuage and interact with Aubergine, a PIWI class protein.
      Mutations in zuc and squ induce the upregulation of Het-A and Tart, two telomere
      specific transposable elements, and the expression of Stellate protein in the
      Drosophila germline. We show that these defects are due to the inability of zuc
      and squ mutants to produce repeat-associated small interfering RNAs.

PMID- 17543860
TI  - SUN1 is required for telomere attachment to nuclear envelope and gametogenesis in
      mice.
AB  - Prior to the pairing and recombination between homologous chromosomes during
      meiosis, telomeres attach to the nuclear envelope and form a transient cluster.
      However, the protein factors mediating meiotic telomere attachment to the nuclear
      envelope and the requirement of this attachment for homolog pairing and synapsis
      have not been determined in animals. Here we show that the inner nuclear membrane
      protein SUN1 specifically associates with telomeres between the leptotene and
      diplotene stages during meiotic prophase I. Disruption of Sun1 in mice prevents
      telomere attachment to the nuclear envelope, efficient homolog pairing, and
      synapsis formation in meiosis. Massive apoptotic events are induced in the mutant
      gonads, leading to the abolishment of both spermatogenesis and oogenesis. This
      study provides genetic evidence that SUN1-telomere interaction is essential for
      telomere dynamic movement and is required for efficient homologous chromosome
      pairing/synapsis during mammalian gametogenesis.

PMID- 17543861
TI  - The nuclear envelope protein Matefin/SUN-1 is required for homologous pairing in
      C. elegans meiosis.
AB  - We identify a highly specific mutation (jf18) in the Caenorhabditis elegans
      nuclear envelope protein matefin MTF-1/SUN-1 that provides direct evidence for
      active involvement of the nuclear envelope in homologous chromosome pairing in C.
      elegans meiosis. The reorganization of chromatin in early meiosis is disrupted in
      mtf-1/sun-1(jf18) gonads, concomitant with the absence of presynaptic homolog
      alignment. Synapsis is established precociously and nonhomologously. Wild-type
      leptotene/zygotene nuclei show patch-like aggregations of the ZYG-12 protein,
      which fail to develop in mtf-1/sun-1(jf18) mutants. These patches remarkably
      colocalize with a component of the cis-acting chromosomal pairing center (HIM-8)
      rather than the centrosome. Our data on this mtf-1/sun-1 allele challenge the
      previously postulated role of the centrosome/spindle organizing center in
      chromosome pairing, and clearly support a role for MTF-1/SUN-1 in meiotic
      chromosome reorganization and in homolog recognition, possibly by mediating local
      aggregation of the ZYG-12 protein in meiotic nuclei.

PMID- 17543862
TI  - A Cul3-based E3 ligase removes Aurora B from mitotic chromosomes, regulating
      mitotic progression and completion of cytokinesis in human cells.
AB  - Faithful cell-cycle progression is tightly controlled by the ubiquitin-proteasome
      system. Here we identify a human Cullin 3-based E3 ligase (Cul3) which is
      essential for mitotic division. In a complex with the substrate-specific adaptors
      KLHL9 and KLHL13, Cul3 is required for correct chromosome alignment in metaphase,
      proper midzone and midbody formation, and completion of cytokinesis. This Cul3
      based E3 ligase removes components of the chromosomal passenger complex from
      mitotic chromosomes and allows their accumulation on the central spindle during
      anaphase. Aurora B directly binds to the substrate-recognition domain of KLHL9
      and KLHL13 in vitro, and coimmunoprecipitates with the Cul3 complex during
      mitosis. Moreover, Aurora B is ubiquitylated in a Cul3-dependent manner in vivo,
      and by reconstituted Cul3/KLHL9/KLHL13 ligase in vitro. We thus propose that the
      Cul3/KLHL9/KLHL13 E3 ligase controls the dynamic behavior of Aurora B on mitotic
      chromosomes, and thereby coordinates faithful mitotic progression and completion
      of cytokinesis.

PMID- 17543863
TI  - The golgi comprises a paired stack that is separated at G2 by modulation of the
      actin cytoskeleton through Abi and Scar/WAVE.
AB  - During the cell cycle, the Golgi, like other organelles, has to be duplicated in
      mass and number to ensure its correct segregation between the two daughter cells.
      It remains unclear, however, when and how this occurs. Here we show that in
      Drosophila S2 cells, the Golgi likely duplicates in mass to form a paired
      structure during G1/S phase and remains so until G2 when the two stacks separate,
      ready for entry into mitosis. We show that pairing requires an intact actin
      cytoskeleton which in turn depends on Abi/Scar but not WASP. This actin-dependent
      pairing is not limited to flies but also occurs in mammalian cells. We further
      show that preventing the Golgi stack separation at G2 blocks entry into mitosis,
      suggesting that this paired organization is part of the mitotic checkpoint,
      similar to what has been proposed in mammalian cells.

PMID- 17543864
TI  - Asymmetric CLASP-dependent nucleation of noncentrosomal microtubules at the trans
      Golgi network.
AB  - Proper organization of microtubule arrays is essential for intracellular
      trafficking and cell motility. It is generally assumed that most if not all
      microtubules in vertebrate somatic cells are formed by the centrosome. Here we
      demonstrate that a large number of microtubules in untreated human cells
      originate from the Golgi apparatus in a centrosome-independent manner. Both
      centrosomal and Golgi-emanating microtubules need gamma-tubulin for nucleation.
      Additionally, formation of microtubules at the Golgi requires CLASPs, microtubule
      binding proteins that selectively coat noncentrosomal microtubule seeds. We show
      that CLASPs are recruited to the trans-Golgi network (TGN) at the Golgi periphery
      by the TGN protein GCC185. In sharp contrast to radial centrosomal arrays,
      microtubules nucleated at the peripheral Golgi compartment are preferentially
      oriented toward the leading edge in motile cells. We propose that Golgi-emanating
      microtubules contribute to the asymmetric microtubule networks in polarized cells
      and support diverse processes including post-Golgi transport to the cell front.

PMID- 17543865
TI  - Visualization of cartilage formation: insight into cellular properties of
      skeletal progenitors and chondrodysplasia syndromes.
AB  - The cellular events underlying skeletal morphogenesis and the formation of
      cartilage templates are largely unknown. We generated an imaging system to
      dynamically visualize limb mesenchymal cells undergoing successive phases in
      cartilage formation and to delineate the cellular function of key regulators of
      chondrogenesis found mutated in chondrodysplasia syndromes. We uncovered an
      unsuspected role for Sox9 in control of cell morphology, independent from its
      major downstream target ColIIa, critically required for the mesenchyme-to
      chondrocyte transition. In contrast, Bmp signaling regulates a cellular program
      we term "compaction" in which mesenchymal cells acquire a cohesive cell behavior
      required to delineate the boundaries and size of cartilage elements. Moreover, we
      visualized labeled progenitor cells from different regions of the limb bud and
      identified unique cellular properties that may direct their contribution toward
      specific skeletal elements such as the humerus or digits. These findings shed
      light on the cellular basis for chondrodysplasia syndromes and formation of the
      vertebrate skeleton.

PMID- 17543866
TI  - RPK1 and TOAD2 are two receptor-like kinases redundantly required for arabidopsis
      embryonic pattern formation.
AB  - Although the basic plant body plan is established during embryogenesis, the
      molecular basis of embryonic patterning remains to be fully understood. We have
      identified two receptor-like kinases, RECEPTOR-LIKE PROTEIN KINASE1 (RPK1) and
      TOADSTOOL2 (TOAD2), required for Arabidopsis embryonic pattern formation. Genetic
      analysis indicates that RPK1 and TOAD2 have overlapping embryonic functions. The
      zygotic gene dosage of TOAD2 in an rpk1 background is of critical importance,
      suggesting that signaling mediated by RPK1 and TOAD2 must be above a threshold
      level for proper embryo development. The localization of RPK1 and TOAD2
      translational fusions to GFP coupled with the analysis of cell-type-specific
      markers indicate that RPK1 and TOAD2 are redundantly required for both pattern
      formation along the radial axis and differentiation of the basal pole during
      early embryogenesis. We propose that RPK1 and TOAD2 receive intercellular signals
      and mediate intracellular responses that are necessary for embryonic pattern
      formation.

PMID- 17543867
TI  - Functional redundancy of GSK-3alpha and GSK-3beta in Wnt/beta-catenin signaling
      shown by using an allelic series of embryonic stem cell lines.
AB  - In mammalian cells, glycogen synthase kinase-3 (GSK-3) exists as two homologs,
      GSK-3alpha and GSK-3beta, encoded by independent genes, which share similar
      kinase domains but differ substantially in their termini. Here, we describe the
      generation of an allelic series of mouse embryonic stem cell (ESC) lines with 0-4
      functional GSK-3 alleles and examine GSK-3-isoform function in Wnt/beta-catenin
      signaling. No compensatory upregulation in GSK-3 protein levels or activity was
      detected in cells lacking either GSK-3alpha or GSK-3beta, and Wnt/beta-catenin
      signaling was normal. Only in cells lacking three or all four of the alleles was
      a gene-dosage effect on beta-catenin/TCF-mediated transcription observed. Indeed,
      GSK-3alpha/beta double-knockout ESCs displayed hyperactivated Wnt/beta-catenin
      signaling and were severely compromised in their ability to differentiate, but
      could be rescued to normality by re-expression of functional GSK-3. The
      rheostatic regulation of GSK-3 highlights the importance of considering the
      contributions of both homologs when studying GSK-3 functions in mammalian
      systems.

PMID- 17543868
TI  - The Vps27/Hse1 complex is a GAT domain-based scaffold for ubiquitin-dependent
      sorting.
AB  - The yeast Vps27/Hse1 complex and the homologous mammalian Hrs/STAM complex
      deliver ubiquitinated transmembrane proteins to the ESCRT endosomal-sorting
      pathway. The Vps27/Hse1 complex directly binds to ubiquitinated transmembrane
      proteins and recruits both ubiquitin ligases and deubiquitinating enzymes. We
      have solved the crystal structure of the core responsible for the assembly of the
      Vps27/Hse1 complex at 3.0 A resolution. The structure consists of two intertwined
      GAT domains, each consisting of two helices from one subunit and one from the
      other. The two GAT domains are connected by an antiparallel coiled coil, forming
      a 90 A-long barbell-like structure. This structure places the domains of Vps27
      and Hse1 that recruit ubiquitinated cargo and deubiquitinating enzymes close to
      each other. Coarse-grained Monte Carlo simulations of the Vps27/Hse1 complex on a
      membrane show how the complex binds cooperatively to lipids and ubiquitinated
      membrane proteins and acts as a scaffold for ubiquitination reactions.

PMID- 17543869
TI  - Polarity determinants Tea1p, Tea4p, and Pom1p inhibit division-septum assembly at
      cell ends in fission yeast.
AB  - Correct positioning of the cell-division plane is crucial for cell function in
      all organisms. The fission yeast Schizosaccharomyces pombe divides by utilizing
      an actomyosin-based contractile ring and is an attractive model for the study of
      cytokinesis. The metazoan anillin-related protein Mid1p stimulates medial
      assembly of the division septum by recruiting actomyosin-ring components to the
      medial cortex. Here, we describe an inhibitory mechanism, involving the cell-end
      localized polarity determinants Tea1p, Tea4p/Wsh3p, and Pom1p (tip complex),
      which prevents division-septum assembly at the cell ends. While Mid1p and the tip
      complex are dispensable for cell viability, their simultaneous loss leads to
      lethality. The FER/CIP homology protein Cdc15p, which organizes the actomyosin
      ring and cell membranes during cytokinesis, is a candidate for regulation by the
      tip complex. Since dual regulation of division-site placement is also seen in
      nematodes, such regulation might be a general feature of eukaryotic cytokinesis.

PMID- 17543870
TI  - Cellular and molecular mechanisms of border cell migration analyzed using time
      lapse live-cell imaging.
AB  - Border cells in the Drosophila ovary originate within an epithelium, detach from
      it, invade neighboring nurse cells, and migrate as a coherent cluster. This
      migration has served as a useful genetic model for understanding epithelial cell
      motility. The prevailing model of growth factor-mediated chemotaxis in general,
      and of border cells in particular, posits that receptor activation promotes
      cellular protrusion at the leading edge. Here we report the time-lapse video
      imaging of border cell migration, allowing us to test this model. Reducing the
      activities of the guidance receptors EGFR and PVR did not result in the expected
      inhibition of protrusion, but instead resulted in protrusion in all directions.
      In contrast, reduction in Notch activity resulted in failure of the cells to
      detach from the epithelium without affecting direction sensing. These
      observations provide new insight into the cellular dynamics and molecular
      mechanisms of cell migration in vivo.

PMID- 17543871
TI  - A retrospective study of rabies in humans in Zimbabwe, between 1992 and 2003.
AB  - This study aimed at examining the epidemiological features of rabies in humans in
      Zimbabwe. The data were taken from internal reports of the department of
      veterinary technical services at Harare covering the period 1st January 1992-31st
      December 2003 inclusive. Positive cases were examined in relation to age and sex
      of the victim, animal vector involved, season, and land-use categories. The
      majority of the confirmed positive human cases (85.7%) were recorded in communal
      areas. The 5-19 year age group and males constituted a highly vulnerable group.
      Over 90% of the cases were due to dog bites with jackals (Canis adustus and C.
      mesomelas), and honey badgers (Mellivora capensis) also contributing to the
      positive cases. Rabid cats and rabid wild animals had a high relative risk (RR)
      of biting humans. Animal-to-human transmission was highest during the dry months
      of July to November.

PMID- 17543872
TI  - Assessing malaria burden during pregnancy in Mali.
AB  - Malaria infection during pregnancy is associated with adverse consequences
      including low birth weight (LBW) and maternal anemia, particularly in
      primigravidae and secundigravidae. In preparation for a clinical trial of the
      efficacy of chloroquine (CQ) and sulfadoxine-pyrimethamine (SP) containing
      prevention regimens during pregnancy, we conducted a one-year cross sectional
      study in Koro and Bandiagara, Mali using an assessment methodology developed by
      the Centers for Disease Control and Prevention (CDC) to generate basic data on
      malarial burden during pregnancy. Two hundred and sixty-one and 192 women were
      enrolled in Koro and Bandiagara, respectively. Rates of placental parasitemia
      were 17.1 and 42.3% in Koro and Bandiagara, respectively, despite high (70-80%)
      use of preventive medication (mainly CQ). Low gravidity (1st and 2nd pregnancies)
      was associated with peripheral (p<0.001) and placental (p<0.001) malaria only in
      Bandiagara, whereas it was associated with low birth weight in both sites
      (p<0.001 in Koro and p=0.002 in Bandiagara). First and second pregnancies were
      the most important characteristics associated with placental malaria (RR=2.78,
      95%CI 1.81-4.29) and (ARR=2.06, 95%CI 1.03-4.15) and low birth weight (RR=4.26,
      95%CI 2.50-7.27) and (ARR=4.51, 95%CI 2.55-8.00). Birth during the rainy season
      was associated with placental infection in univariate analysis. Characteristics
      such as younger age, having fever during pregnancy, and unmarried status were
      associated with low birth weight only in univariate analysis and singleton
      premature delivery and low gravidity were associated with low birth weight in
      both univariate and multivariate analysis. Data from this assessment demonstrated
      the high burden of malaria during pregnancy in Mali. Results had been used by
      researchers as local reference data and by ministry of health for to stop
      recommending CQ prophylaxis. The methodology could be used by other malaria
      endemic countries to direct their national malaria program efforts.

PMID- 17543873
TI  - Integrated investigations of the electrosurface properties of nonaqueous disperse
      and capillary systems.
AB  - Survey of the experimental results obtained in the Department of Colloid
      Chemistry of St. Petersburg State University on the integrated investigations of
      the electrosurface properties of various nonaqueous disperse and capillary
      systems covering a wide range of electrolyte solutions in various organic
      solvents: amphoteric ethanol and 1-butanol; dipolar aprotic dimethylsulfoxide,
      dimethylformamide, acetone and nitromethane; nonpolar n-heptane in contact with
      SiO2, TiO2, Al2O3 and glass. Electrokinetic potential zeta and charge
      sigma(zeta), adsorption of ions Gamma, surface conductivity Ks of powdery silica,
      titania and alumina were determined depending on the concentration 10(-5)-10(-2)
      M of LiBr, KBr, NaBr, CsBr, HBr, NaCl, NaOH, HCl, various tetraalkylammonium
      bromides and ionic surfactants in the above cited solvents. Special attention was
      paid to the consistency of the results of zeta-potential evaluation obtained from
      the streaming potential and electrophoretic mobility data using the most commonly
      known theoretical expressions. It was shown that the surface conductivity must be
      taken into account in all cases for the evaluation of correct zeta-potential
      values. The surface conductivity and zeta-potential for the porous quartz plugs
      and glass membranes were determined as the functions of concentration of the
      anionic surfactants in n-heptane containing controlled traces of water. It was
      also shown that in the cases of the less polar solvents and more polar solids the
      enormous values of surface conductivity are due to the adsorption of the traces
      of water and in the cases of more hydrophylic liquids due to the overall
      adsorption of all ionic components from the solutions.

PMID- 17543874
TI  - Intercurrent factors associated with the development of open-angle glaucoma in
      the European glaucoma prevention study.
AB  - PURPOSE: To evaluate the intercurrent factors for the development of open-angle
      glaucoma (OAG) in ocular hypertensive patients who were enrolled in the European
      Glaucoma Prevention Study (EGPS). DESIGN: Randomized, double masked, controlled
      clinical trial. METHODS: setting: Multicenter. study population: A total of 1,077
      patients fulfilled a series of inclusion criteria, including intraocular pressure
      (IOP) 22 to 29 mm Hg, normal and reliable visual fields (VFs) and normal optic
      disks. intervention: Treatment with dorzolamide or placebo. main outcome
      measures: Glaucoma-related VF or optic disk changes. Clinical data were collected
      every six months during a five-year follow-up. Proportional hazards models were
      used to identify the factors that during follow-up (intercurrent factors) were
      associated with the development of OAG. RESULTS: In multivariate analyses,
      adjusting for treatment arms and baseline predictive factors, mean follow-up IOP
      reduction (hazard ratio [HR] 0.89, 95% confidence intervals [CI] 0.80 to 0.98),
      mean follow-up IOP (HR 1.12, 95% CI 1.03 to 1.22), area under the curve of IOP
      (mm Hg per year) (HR 1.09, 95% CI 1.06 to 1.12), disk hemorrhages (HR 1.97, 95%
      CI 1.21 to 3.22), and use of systemic diuretics (HR 2.41, 95% CI 1.12 to 5.19)
      were associated with the development of OAG. Baseline central corneal thickness,
      vertical cup/disk ratio, vertical cup/disk ratio asymmetry, and pattern standard
      deviation remained statistically significant. CONCLUSIONS: These results suggest
      the need for future investigations to better elucidate the role of systemic
      diuretics in the development of OAG, because IOP and disk hemorrhages have
      already been shown to be important intercurrent factors in the Ocular
      Hypertension Treatment Study (OHTS) and Early Manifest Glaucoma Trial (EMGT).

PMID- 17543875
TI  - Outcomes of Boston keratoprosthesis in aniridia: a retrospective multicenter
      study.
AB  - PURPOSE: To evaluate the long-term outcomes of keratoprosthesis as an alternative
      surgical procedure in the management of aniridic keratopathy. DESIGN:
      Retrospective, multicenter case series. METHODS: Fifteen adult patients (16 eyes)
      with aniridia who were deemed at high risk for regular donor corneal
      transplantation underwent a Boston type I keratoprosthesis procedure for visual
      rehabilitation. Device retention rate, preoperative and postoperative visual
      acuity, and intraoperative and postoperative complications were studied. RESULTS:
      The mean age of the patients was 45 (median 50) years. Six of the patients were
      females. Eleven patients had previously undergone donor corneal transplantations
      (average two grafts), with failure. In 10 patients, the keratoprosthesis surgery
      was combined with other procedures such as cataract extraction, tube shunt
      implantation, vitrectomy, and intraocular lens removal. No intraoperative
      complications were encountered. The follow-up ranged from two months to 85
      months, with a median of 17 months. All devices remained in situ throughout the
      entire follow-up period. The visual acuity improved in all but one patient from a
      median of counting fingers (light perception to 20/300) to 20/200 (hand motions
      to 20/60). Comorbid preoperative conditions particularly optic nerve and foveal
      hypoplasia limited the final postoperative vision. No endophthalmitis or
      extrusion of the device occurred. One device required repair procedure without
      necessitating a removal. CONCLUSIONS: Keratoprosthesis offers significant vision
      benefits in this patient group.

PMID- 17543876
TI  - Reopening of previously closed macular holes after cataract extraction.
AB  - PURPOSE: To evaluate the frequency of reopening of macular holes after cataract
      extraction. DESIGN: Retrospective, comparative, consecutive case series. METHODS:
      Two hundred and eleven eyes with idiopathic macular holes closed by vitrectomy
      were divided into four groups: Group 1: prior cataract extraction; Group 2:
      vitrectomy then cataract extraction; Group 3: vitrectomy only; and Group 4:
      vitrectomy and cataract extraction as a combined procedure. The main outcome
      measure of macular hole reopening was evaluated in relationship to multiple
      variables. RESULTS: Two hundred and eleven eyes were included: Group 1: 56 eyes;
      Group 2: 86 eyes; Group 3: 41 eyes; and Group 4: 28 eyes. Twenty-four macular
      holes reopened (11%) (mean follow-up 26.6 months, range, three to 118 months).
      The greatest number of macular hole reopenings, 17 (20%), were in Group 2. Cox
      multivariate analysis failed to demonstrate an association between duration of
      hole, serum use, internal limiting membrane peeling, or stage and reopening of a
      macular hole. Cox analysis showed a four-fold increased risk of reopening in
      Group 2 eyes (95% confidence interval [CI]: 1.7 to 11.2; P = .002). Eyes with
      cystoid macular edema after cataract extraction had a seven-fold increased risk
      of macular hole reopening (7.72; 95% CI: 2.79 to 21.3; P < .0005). Kaplan-Meier
      analysis showed increased rates of macular hole reopening in Group 2 eyes
      compared to the other 3 groups combined (log-rank P < .00005). CONCLUSIONS:
      Cataract extraction after successful vitrectomy for macular hole, when
      complicated by cystoid macular edema (CME), may increase the risk of macular hole
      reopening.

PMID- 17543877
TI  - Real-time monitoring of cell-free protein synthesis on a surface plasmon
      resonance chip.
AB  - Taking advantage of the "open" nature of cell-free protein synthesis, this study
      investigated the direct analysis of protein expression using a surface plasmon
      resonance sensor. During the on-chip incubation of the reaction mixture for cell
      free protein synthesis, the expressed protein molecules were immobilized onto the
      surface of the chip, giving rise to a sensorgram signal, which enabled on-line
      monitoring of protein expression. In addition, we found that the expression of
      the aggregation-prone proteins could be effectively monitored. The ability to
      monitor these proteins was most likely through the instant isolation of the
      expressed protein molecules onto the solid surface of the chip.

PMID- 17543878
TI  - Use of a fluorescence lifetime imaging microscope in an apoptosis assay of
      Ewing's sarcoma cells with a vital fluorescent probe.
AB  - A fluorescence lifetime imaging microscope (FLIM) was applied to study early
      stage apoptotic cells stained with a SYTO13 dye. The fluorescence lifetime of
      SYTO13 in healthy cells was 3.8+/-0.3ns but was reduced to 2.4+/-0.4 and 1.9+/
      0.2ns after a 3-h period of incubation with SYTO13 when doxorubicin, a known
      inducer of apoptosis, was added to human Ewing's family tumor cells at final
      concentrations of 250 and 500nM, respectively, in a dose-dependent experiment. On
      the other hand, in a time-dependent experiment, the fluorescence lifetime
      decreased to 2.5+/-0.5 and 1.7+/-0.4ns at a doxorubicin concentration of 750nM
      after 2 and 4h, respectively. A possible explanation for these results is self
      quenching induced by a change in interprobe distance that arises from the
      condensation of DNA during apoptosis. In this study, the FLIM system was employed
      to investigate early-stage apoptosis that involves only small morphological
      changes, suggesting the potential advantage of this method for evaluating small
      biological effects in living cells.

PMID- 17543879
TI  - Postural support strategies of disabled drivers and the effectiveness of postural
      support aids.
AB  - The paper discusses a series of driving trials that were conducted to investigate
      postural stability of disabled drivers and to assess the effectiveness of a
      representative sample of support aids. Twenty-three disabled drivers with varying
      levels of physical disability and seven non disabled drivers participated in the
      study. The test car was equipped with transducers to measure vehicle velocity and
      acceleration (longitudinal and lateral), steering wheel movement and torque, and
      the bracing forces exerted by the driver on the steering wheel. Video cameras
      were installed to record postural support strategies and displacement of the
      driver and to record deviation of the car from the specified path. Subjective
      data regarding driver attitudes and acceptance were also collected through the
      administration of questionnaires. Findings from the study showed that support
      aids significantly improved driving performance and reduced physical exertion to
      maintain an upright driving position for disabled drivers. However, ergonomics
      design aspects regarding the ease of use and acceptance of the support aids by
      the end users were identified as obstacles to their sustained use in everyday
      driving.

PMID- 17543880
TI  - Involvement of SNARE proteins in thrombin-induced platelet aggregation: evidence
      for the relevance of Ca2+ entry.
AB  - Thrombin induces platelet activation through a variety of intracellular
      mechanisms, including Ca(2+) mobilization. The protein of the exocytotic
      machinery SNAP-25, but not VAMPs, is required for store-operated Ca(2+) entry,
      the main mechanism for Ca(2+) influx in platelets. Hence, we have investigated
      the role of the SNAP-25 and VAMPs in thrombin-induced platelet aggregation.
      Platelet stimulation with thrombin or selective activation of thrombin receptors
      PAR-1, PAR-4 or GPIb-IX-V results in platelet aggregation that, except for GPIb
      IX-V receptor, requires Ca(2+) entry for full activation. Depletion of the
      intracellular Ca(2+) stores using pharmacological tools was unable to induce
      aggregation except when cytosolic Ca(2+) concentration reached a critical level
      (around 1.5 microM). Electrotransjection of cells with anti-SNAP-25 antibody
      reduced thrombin-evoked platelet aggregation, while electrotransjection of anti
      VAMP-1, -2 and -3 antibody had no effect. These findings support a role for SNAP
      25 but not VAMP-1, -2 and -3 in platelet aggregation, which is likely mediated by
      the regulation of Ca(2+) mobilization in human platelets.

PMID- 17543881
TI  - Use of SILAC for exploring sheddase and matrix degradation of fibroblasts in
      culture by the PIII SVMP atrolysin A: identification of two novel substrates with
      functional relevance.
AB  - Snake venom metalloproteinases (SVMPs) in Viperid venoms primarily function to
      give rise to local and systemic hemorrhage following snake envenomation. Years of
      research on these toxins, both in vitro and in vivo, indicate that they function
      by disrupting capillary basement membranes, stromal matrix and cell-cell and cell
      matrix contacts to allow escape of capillary contents under pressure. However,
      most of these studies used either defined substrates in vitro or were limited by
      relevant antibodies for detection of sites of action in vivo. In this
      investigation we use stable isotope-labeled amino acids in culture (SILAC) to
      determine novel proteolytic activities for exogenously added atrolysin A, a
      hemorrhagic PIII SVMP isolated from Crotalus atrox venom. When comparing the
      solubilized products of SILAC-labeled cultured human fibroblasts treated with
      atrolysin A to that of untreated fibroblasts using LC/MS/MS, several proteins
      were identified as being released into the culture media specifically due to
      atrolysin A proteolytic activity. These included collagen VI, fibronectin,
      fibulin 2 and annexin V. Of particular interest was the observation of collagen
      VI and annexin V in that the release of these substrates could play a role in
      altering hemostasis and promote hemorrhage caused by the more typical actions of
      atrolysin A. In summary, this study demonstrates the utility of SILAC for
      exploring sheddase activity with cells in culture and suggests the presence of
      two novel substrates for SVMPs that may play a pathological role in altering host
      hemostasis during envenomation.

PMID- 17543882
TI  - Establishment of cell lines that exhibit pluripotency from miniature swine
      periodontal ligaments.
AB  - OBJECTIVE: The periodontal ligament (PDL) is a fibrous connective tissue composed
      of heterogeneous cell types, including PDL fibroblasts. It is not clear whether
      cells within the PDL fibroblast population retain the potency to differentiate
      into other cell types. DESIGN: In the present study, clonal cell lines, derived
      from Clawn miniature swine PDLs, were established by gene transfection for a
      human telomerase reverse transcriptase, and characterized. RESULTS: These cell
      lines, denoted TesPDL1-4, had PDL fibroblasts that showed fibroblastic morphology
      and expressed procollagen alpha1(I), osteopontin, periostin and alkaline
      phosphatase mRNA. Under the specific culture conditions, TesPDL3 cells also have
      the ability to express CD31, vascular endothelial cadherin, von Willebrand
      factor, osteocalcin, and to form extracellular mineralized nodules. CONCLUSIONS:
      Our data indicate that TesPDL3 cells have unique properties of expressing several
      phenotype of fibroblasts, vascular endothelial cells and osteoblasts in cultures.

PMID- 17543883
TI  - Quality control of Photosystem II: cleavage and aggregation of heat-damaged D1
      protein in spinach thylakoids.
AB  - Moderate heat stress (40 degrees C, 30 min) on spinach thylakoids induced
      cleavage of the D1 protein, producing an N-terminal 23-kDa fragment, a C-terminal
      9-kDa fragment, and aggregation of the D1 protein. A homologue of Arabidopsis
      FtsH2 protease, which is responsible for degradation of the damaged D1 protein,
      was abundant in the stroma thylakoids. Two processes occurred in the thylakoids
      in response to heat stress: dephosphorylation of the D1 protein in the stroma
      thylakoids, and aggregation of the phosphorylated D1 protein in the grana. Heat
      stress also induced the release of the extrinsic PsbO, P and Q proteins from
      Photosystem II, which affected D1 degradation and aggregation significantly. The
      cleavage and aggregation of the D1 protein appear to be two alternative processes
      influenced by protein phosphorylation/dephosphorylation, distribution of FtsH,
      and intactness of the thylakoids.

PMID- 17543884
TI  - Photosynthetic dioxygen formation studied by time-resolved delayed fluorescence
      measurements--method, rationale, and results on the activation energy of dioxygen
      formation.
AB  - The analysis of the time-resolved delayed fluorescence (DF) measurements
      represents an important tool to study quantitatively light-induced electron
      transfer as well as associated processes, e.g. proton movements, at the donor
      side of photosystem II (PSII). This method can provide, inter alia, insights in
      the functionally important inner-protein proton movements, which are hardly
      detectable by conventional spectroscopic approaches. The underlying rationale and
      experimental details of the method are described. The delayed emission of
      chlorophyll fluorescence of highly active PSII membrane particles was measured in
      the time domain from 10 mus to 60 ms after each flash of a train of nanosecond
      laser pulses. Focusing on the oxygen-formation step induced by the third flash,
      we find that the recently reported formation of an S4-intermediate prior to the
      onset of O-O bond formation [M. Haumann, P. Liebisch, C. Muller, M. Barra, M.
      Grabolle, H. Dau, Science 310, 1019-1021, 2006] is a multiphasic process, as
      anticipated for proton movements from the manganese complex of PSII to the
      aqueous bulk phase. The S4-formation involves three or more likely sequential
      steps; a tri-exponential fit yields time constants of 14, 65, and 200 mus (at 20
      degrees C, pH 6.4). We determine that S4-formation is characterized by a sizable
      difference in Gibbs free energy of more than 90 meV (20 degrees C, pH 6.4). In
      the second part of the study, the temperature dependence (-2.7 to 27.5 degrees C)
      of the rate constant of dioxygen formation (600/s at 20 degrees C) was
      investigated by analysis of DF transients. If the activation energy is assumed to
      be temperature-independent, a value of 230 meV is determined. There are weak
      indications for a biphasicity in the Arrhenius plot, but clear-cut evidence for a
      temperature-dependent switch between two activation energies, which would point
      to the existence of two distinct rate-limiting steps, is not obtained.

PMID- 17543885
TI  - Expression of Caveolin-1 reduces cellular responses to TGF-beta1 through down
      regulating the expression of TGF-beta type II receptor gene in NIH3T3 fibroblast
      cells.
AB  - Transcriptional repression of Transforming Growth Factor-beta type II receptor
      (TbetaRII) gene has been proposed to be one of the major mechanisms leading to
      TGF-beta resistance. In this study, we demonstrate that expression of Caveolin-1
      (Cav-1) gene in NIH3T3 fibroblast cells down-regulates the expression of TbetaRII
      gene in the transcriptional level, eventually resulting in the decreased
      responses to TGF-beta. The reduced expression of TbetaRII gene by Cav-1 appeared
      to be due to the changes of the sequence-specific DNA binding proteins to either
      Positive Regulatory Element 1 (PRE1) or PRE2 of the TbetaRII promoter. In
      addition, Cav-1 expression inhibited TGF-beta-mediated cellular proliferation and
      Plasminogen Activator Inhibitor (PAI)-1 gene expression as well as TGF-beta
      induced luciferase activity. Furthermore, the inhibition of endogeneous Cav-1 by
      small interfering RNA increased the expression of TbetaRII gene. These findings
      strongly suggest that expression of Cav-1 leads to the decreased cellular
      responsiveness to TGF-beta through down-regulating TbetaRII gene expression.

PMID- 17543886
TI  - Increased oxidative damage and mitochondrial abnormalities in the peripheral
      blood of Huntington's disease patients.
AB  - Increased oxidative stress and mitochondrial abnormalities contribute to neuronal
      dysfunction in Huntington's disease (HD). We investigated whether these
      pathological changes in HD brains may also be present in peripheral tissues.
      Leukocyte 8-hydroxydeoxyguanosine (8-OHdG) and plasma malondialdehyde (MDA) were
      elevated, and activities of erythrocyte Cu/Zn-superoxide dismutase (Cu/Zn-SOD)
      and glutathione peroxidase (GPx) reduced in 16 HD patients when compared to 36
      age- and gender-matched controls. Deleted and total mitochondrial DNA (mtDNA)
      copy numbers were increased, whereas the mRNA expression levels of mtDNA-encoded
      mitochondrial enzymes are not elevated in HD leukocytes compared to the normal
      controls. Plasma MDA levels also significantly correlated with HD disease
      severity. These results indicate means to suppress oxidative damage or to restore
      mitochondrial functions may be beneficial to HD patients. Plasma MDA may be used
      as a potential biomarker to test treatment efficacy in the future, if confirmed
      in a larger, longitudinal study.

PMID- 17543887
TI  - An anti-endotoxin peptide that generates from the amino-terminal domain of
      complement regulatory protein C1 inhibitor.
AB  - C1 inhibitor (C1INH), a complement regulatory protein, prevents endotoxin shock
      via a direct interaction of the amino-terminal domain with gram-negative
      bacterial lipopolysaccharide (LPS). Importantly, the cleaved, inactive C1INH
      still is an anti-endotoxin effector indicating the anti-endotoxin peptide that
      generates from the amino-terminal domain of C1INH. In this study, we first
      identified that a cleaved fragment within the major part of the amino-terminal
      domain in in vitro proteolytic analysis of C1INH had an ability to bind to LPS.
      We synthesized several peptides overlapping the C1INH cleaved fragment. Among
      these synthetic peptides, a 13-mer derivative peptide at position from 18 to 30,
      named N2((18-30)), exhibited the most powerful anti-endotoxin activity in vitro,
      enlightening that it was most strong at binding to LPS, inhibiting the
      interaction of LPS with LPS-binding protein (LBP), blocking LPS binding to
      CD14(+) cells, and suppressing production of tumor necrosis factor (TNF)-alpha by
      murine macrophages, RAW 264.7. In the murine endotoxin shock model, the peptide
      N2((18-30)) protected mice from LPS-induced lethal septic shock by inhibiting
      macrophage activation. These data indicate that the peptide N2((18-30)) derived
      from the amino-terminal region of C1INH is anti-endotoxin.

PMID- 17543888
TI  - The hereditary hemochromatosis protein HFE and its chaperone beta2-microglobulin
      localise predominantly to the endosomal-recycling compartment.
AB  - Hereditary Hemochromatosis is an iron overload disease most frequently associated
      with mutations in the HFE gene. While clinical studies of the disease have
      received extensive attention by various groups, the localisation, trafficking and
      function of the HFE protein, and its chaperone beta2-microglobulin (beta2M),
      require further investigation. In this study, we present data on the cellular
      localisation of HFE and its clinically relevant mutants in HuTu 80 cells. We find
      by confocal microscopy that HFE localises to the endosomal-recycling compartment
      (ERC), with minimal localisation to sorting or late endosomes. Interestingly, we
      also demonstrate that beta2M localises to the ERC where it co-localises with HFE.
      We find that exogenous expression of HFE results in enhanced beta2M cellular
      levels and that beta2M is necessary for cell surface expression of HFE. Finally,
      we have analysed the functional effects of exogenous expression of HFE and beta2M
      on transferrin binding to the cell surface. In summary, our study sheds light on
      the localisation and functional effects of the HFE and its chaperone protein
      beta2M.

PMID- 17543889
TI  - Family 18 chitolectins: comparison of MGP40 and HUMGP39.
AB  - Glycosidase and lectins both bind sugars, but only the glycosidases have
      catalytic activity. The glycosidases occur among over 100 evolved protein
      families and Family 18 is one of the two chitinases (EC 3, 2.1.14) families.
      Interestingly, lectins are also in this evolutionary group of Family 18
      glycosidase proteins. The proteins belonging to the enzymatically inactive class
      are referred to as chitolectins and have a binding site that is highly similar to
      the catalytic Family 18 enzymes. We present a comparison of the recently obtained
      structures of two Family 18 chitolectins, MGP40 [A.K. Mohanty, G. Singh, M.
      Paramasivam, K. Saravanan, T. Jabeen, S. Sharma, S. Yadav, P. Kaur, P. Kumar, A.
      Srinivasan, T.P. Singh, Crystal structure of a novel regulatory 40kDa mammary
      gland protein (MGP-40) secreted during involution, J. Biol. Chem. 278 (2003)
      14451-14460.] and HumGP39 [F. Fusetti, T. Pijning, K.H. Kalk, E. Bos, B.W.
      Dijkstra, Crystal structure and carbohydrate-binding properties of the human
      cartilage glycoprotein-39, J. Biol. Chem. 278 (2003) 37753-37760; D.R. Houston,
      D.R. Anneliese, C.K. Joanne, D.M.V. Aalten, Structure and ligand-induced
      conformational change of the 39kDa glycoprotein from human articular
      chondrocytes, J. Biol. Chem. 278 (2003) 30206-30212.] with a focus on the
      glycosidase active site. We compare the sequence and the structure of these two
      Family 18 protein classes. The difference between the active and inactive protein
      is a glutamic acid which acts as the essential acid/base residue for chitin
      cleavage and is replaced with leucine or glutamine in the chitolectins.
      Furthermore, a mechanism for the interaction between the chitolectin and
      oligosaccharides was proposed.

PMID- 17543890
TI  - H2B-K123 ubiquitination stimulates RNAPII elongation independent of H3-K4
      methylation.
AB  - Eukaryotic gene regulation is closely correlated with histone covalent
      modifications. Recently, histone H2B lysine-123 (H2B-K123) ubiquitination has
      been implicated in regulation of transcription as well as histone H3 lysine-4 (H3
      K4) methylation which is further associated with active transcription. However,
      whether H2B-K123 ubiquitination controls transcription through regulation of H3
      K4 methylation remains unknown under physiological conditions. Here, we show that
      H2B-K123 ubiquitination enhances the rate of elongating RNA polymerase II
      (RNAPII) recruitment to the coding sequence of an inducible yeast gene, GAL1.
      Consistently, GAL1 transcription is significantly impaired in absence of H2B-K123
      ubiquitination. On the other hand, H3-K4 methylation does not alter the rate of
      elongating RNAPII recruitment at GAL1. Further, these covalent modifications do
      not regulate pre-initiation complex formation at GAL1. Collectively, our data
      demonstrate the function of H2B-K123 ubiquitination in regulation of
      transcriptional elongation independently of H3-K4 methylation in vivo, providing
      a new insight on epigenetic regulation of gene expression.

PMID- 17543891
TI  - Effects of Salviae Mitiorrhizae and Cortex Moutan extract on the rat heart after
      myocardial infarction: a proteomic study.
AB  - In this study, we characterized the therapeutical effects of Salviae Mitiorrhizae
      (Danshen) and Cortex Moutan (Danpi) extract (SDD) on Sprague-Dawley rats
      subjected to coronary artery ligation, and applied proteomic approach to
      investigate its potential mechanism of action. The chemical composition of SDD
      was investigated by HPLC/MS(n) analysis. Measurement for serum levels of creatine
      kinase (CK), creatine kinase-MB (CK-MB), nitrite and histological study for
      infarct area of heart were performed. Moreover, protein abundance profiles of
      myocardium were compared by two-dimensional gel electrophoresis and altered
      proteins were identified by MALDI-TOF-MS. The results showed SDD significantly
      decreased CK, CK-MB concentration in serum and infarct area of heart, while
      increased the release of nitrite in rats with coronary occlusion. Increased
      concentration of ATP and total adenine nucleotide indicated the energy metabolism
      has been improved in ischemic heart induced by SDD. Proteomic data revealed that
      23 proteins associated with energy metabolism, oxidative stress and cytoskeleton
      were modulated in SDD treated rats.

PMID- 17543892
TI  - Fear-potentiated startle to threat, and prepulse inhibition among young adult
      nonsmokers, abstinent smokers, and nonabstinent smokers.
AB  - BACKGROUND: Evidence suggests that the transition from experimental to regular
      smoking is facilitated by the influence of tobacco on affective and attentional
      mechanisms. The objective of this study was to examine affective and attentional
      responses in young adult smokers using fear-potentiated startle and prepulse
      inhibition. METHODS: Participants were 56 college nonsmokers, nonabstinent
      smokers, and overnight-abstinent smokers. The fear-potentiated startle test
      examined phasic responses to imminent threat cues and more sustained responses to
      unpredictable aversive events. Prepulse inhibition investigated responses to
      attended and ignored prepulse stimuli. RESULTS: Abstinent and nonabstinent
      smokers showed increased sustained potentiation of startle to contextual cues,
      compared to controls. Abstinent smokers showed increased fear-potentiated startle
      to threat cues, compared to nonsmokers. PPI did not discriminate between
      abstinent or nonabstinent smokers and controls. CONCLUSIONS: These findings
      suggest that negative affectivity or anxiety is associated with smoking,
      particularly during short withdrawal. Potentiated startle may provide a valuable
      tool in understanding the biologic mechanisms underlying nicotine withdrawal and
      inform cessation and prevention efforts.

PMID- 17543893
TI  - Contribution of methylenetetrahydrofolate reductase (MTHFR) polymorphisms to
      negative symptoms in schizophrenia.
AB  - BACKGROUND: Folate deficiency may contribute to negative symptoms in
      schizophrenia, but the underlying mechanism remains uncertain. We examined
      whether the methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C
      functional polymorphisms contribute to negative symptoms. METHODS: Outpatients
      with schizophrenia (n = 200) were evaluated with the Positive and Negative
      Syndrome Scale (PANSS). Subjects also provided a blood sample for MTHFR genotype
      and serum chemistries. Comparisons of PANSS symptoms, folate, and homocysteine
      status were conducted based on genotype. RESULTS: The 677T allele load was
      associated with negative symptom severity. Contrary to our expectations, the T
      allele was also found to be protective against positive symptoms. The A1298C
      polymorphism did not contribute to negative symptoms, and only weakly to positive
      symptoms. The specific effects of the C677T polymorphism were confirmed with
      haplotype analysis. Among patients homozygous for the 667T allele, serum folate
      levels correlated with negative symptom severity. CONCLUSIONS: Increased MTHFR
      677T allele load confers risk for negative symptoms in schizophrenia, while
      reducing severity of positive symptoms. Further, the biochemical interaction of
      low serum folate with 677T-variant MTHFR may induce downstream effects salient to
      the expression of negative symptoms.

PMID- 17543894
TI  - Six-month prospective life charting of mood symptoms with lamotrigine monotherapy
      versus placebo in rapid cycling bipolar disorder.
AB  - BACKGROUND: Fluctuations in mood are quintessential features of bipolar disorder;
      however, previous studies have seldom examined the extent to which
      pharmacotherapies for bipolar disorder may reduce or ameliorate daily or weekly
      mood variability. The anticonvulsant lamotrigine has demonstrated efficacy for
      relapse prevention in bipolar disorder, but its possible mood-stabilizing
      properties on a day-to-day or week-to-week basis have not previously been
      investigated. METHODS: Weekly mood shifts were examined over 26 weeks using
      patients' self-reported prospective Life Chart Method (LCM) data obtained as part
      of a previously reported randomized relapse prevention comparison of lamotrigine
      monotherapy or placebo in 182 bipolar patients with DSM-IV rapid cycling.
      Generalized estimating equation (GEE) analyses were used to compare treatment
      arms for subjects who achieved euthymia across weeks. RESULTS: After adjusting
      for potential confounding factors, a final GEE model revealed that subjects
      taking lamotrigine were 1.8 times more likely than those taking placebo to
      achieve euthymia, as measured by LCM, at least once per week over 6 months (95%
      confidence interval [CI] = 1.03-3.13). Subjects taking lamotrigine had an
      increase of .69 more days per week euthymic as compared with those taking placebo
      (p = .014). CONCLUSIONS: Achievement of euthymia across weeks represents a novel
      paradigm shift in gauging the mood-stabilizing properties of a psychotropic
      agent. The present findings demonstrate the utility of the prospective Life Chart
      Method for assessing longitudinal mood stability during randomized clinical
      trials for bipolar disorder. The results lend support to the potential mood
      stabilizing properties of lamotrigine monotherapy for bipolar disorder.

PMID- 17543895
TI  - The neuropsychological effects of chronic methylphenidate on drug-naive boys with
      attention-deficit/hyperactivity disorder.
AB  - BACKGROUND: The reported neuropsychological effects of methylphenidate (MPH) in
      attention-deficit/hyperactivity disorder (ADHD) are inconsistent. The assumed
      relationships between these neuropsychological effects and clinical efficacy have
      not been substantiated. We therefore investigated the effects of chronic MPH
      administration on neuropsychological functioning. METHODS: We conducted a 12
      week, placebo-controlled, double-blinded, randomized, crossover trial (MPH .3 and
      .6 mg/kg/dose and placebo). Participants were 75 boys aged 7-15 years with ADHD.
      Neuropsychological performance was assessed with tests taken from the Cambridge
      Neuropsychological Test Automated Battery (CANTAB) battery and a GoNoGo task.
      RESULTS: Chronic MPH improved performance (p < .001) on aspects of the GoNoGo
      task (p < .02) and on three CANTAB tasks which together contributed to a
      "recognition memory" component identified through principal components analysis
      (delayed matching to sample [DMtS], pattern and spatial recognition). There were
      no effects on other, high or low "executive demand" tasks (p > .05). GoNoGo
      performance improvements were the only neuropsychopharmacological changes
      associated with clinical response. Poor performance on the DMtS task was the sole
      baseline neuropsychological predictor of clinical response. CONCLUSIONS: Chronic
      MPH predominantly enhanced neuropsychological functioning on "recognition memory"
      component tasks with modest "executive" demands. Neuropsychological measures
      offer only modest contributions to the prediction of clinical responses to MPH in
      ADHD.

PMID- 17543896
TI  - Influence of emotional expression on memory recognition bias: a functional
      magnetic resonance imaging study.
AB  - BACKGROUND: Most studies of the influence of emotion on memory performance have
      focused on accuracy. However, there is evidence that emotion can influence other
      aspects of memory, in particular response bias (overall tendency to classify
      items as new or old regardless of the accuracy of the response). Here we
      investigated the behavioral and neural-related modulation of response bias by
      emotion. METHODS: Nineteen healthy individuals performed a recognition memory
      task on faces with happy, sad, and neutral expressions while undergoing
      functional magnetic resonance imaging (fMRI). RESULTS: We observed a familiarity
      (tendency to say "old") and novelty (tendency to say "new") bias for sad and
      happy faces, respectively. Novelty response bias was associated with amygdala and
      prefrontal cortex activity, whereas familiarity bias correlated with superior
      temporal gyrus activation. CONCLUSIONS: These results show that emotional
      expressions can have an influence on memory beyond simple accuracy and that this
      effect is in part mediated by the amygdala, a region previously implicated in
      emotional perception and memory. Our findings might have important clinical
      relevance, because they could help explain some of the inconsistencies in the
      literature regarding emotional memory deficits in psychiatric populations.

PMID- 17543897
TI  - Excess of high frequency electroencephalogram oscillations in boys with autism.
AB  - BACKGROUND: An elevated excitation/inhibition ratio has been suggested as one
      mechanism underpinning autism. An imbalance between cortical excitation and
      inhibition may manifest itself in electroencephalogram (EEG) abnormalities in the
      high frequency range. The aim of this study was to investigate whether beta and
      gamma range EEG abnormalities are characteristic for young boys with autism
      (BWA). METHODS: EEG was recorded during sustained visual attention in two
      independent samples of BWA from Moscow and Gothenburg, aged 3 to 8 years, and in
      age matched typically developing boys (TDB). High frequency EEG spectral power
      was analyzed. RESULTS: In both samples, BWA demonstrated a pathological increase
      of gamma (24.4-44.0 Hz) activity at the electrode locations distant from the
      sources of myogenic artefacts. In both samples, the amount of gamma activity
      correlated positively with degree of developmental delay in BWA. CONCLUSIONS: The
      excess of high frequency oscillations may reflect imbalance in the excitation
      inhibition homeostasis in the cortex. Given the important role of high frequency
      EEG rhythms for perceptual and cognitive processes, early and probably
      genetically determined abnormalities in the neuronal mechanisms generating high
      frequency EEG rhythms may contribute to development of the disorder. Further
      studies are needed to investigate the specificity of the findings for autism.

PMID- 17543898
TI  - Analysis of quantal size of voltage responses to retinal stimulation in the
      accessory optic system.
AB  - In the intact vertebrate central nervous system, the quantal nature of synaptic
      transmission is difficult to measure because the postsynaptic sites may be
      distributed along a tortuous dendritic tree that cannot be readily clamped
      spatially to a uniform potential. Titrating the intact brain's extracellular
      concentration of calcium ions is also challenging because of its strong buffering
      mechanisms. In this study, using a whole brain with eye attached preparation,
      quantal neurotransmission was examined in the turtle brainstem in vitro, by
      recording from accessory optic system neurons that receive direct input from
      visually responsive retinal ganglion cells. Unitary EPSPs, evoked by
      microstimulation of a single ganglion cell, were measured during whole cell
      current-clamp recordings. In this preparation, the neurons exhibit direction
      selectivity, despite the hypoxic conditions. Bath application of cadmium to
      reduce calcium influx also reduced evoked EPSP amplitudes to that of the
      spontaneous synaptic events. Statistical analyses indicated that these evoked
      response amplitudes could be well fitted to a Poisson distribution for most
      brainstem neurons. Therefore, the spontaneous miniature excitatory synaptic
      events of approximately 1 mV, as also observed during spike blockade of the
      retina [Kogo, N., Ariel, M., 1997. Membrane properties and monosynaptic retinal
      excitation of neurons in the turtle accessory optic system. Journal of
      Neurophysiology 78, 614-627], are likely responses to the neurotransmitter of
      single vesicles release by retinal axon terminals.

PMID- 17543899
TI  - Evidence for regulation of tyrosine hydroxylase mRNA translation by stress in rat
      adrenal medulla.
AB  - Long-term stress leads to the induction of tyrosine hydroxylase (TH) protein and
      enzymatic activity in the adrenal medulla. This adaptive response is necessary to
      maintain the catecholamine biosynthetic capacity of adrenal chromaffin cells
      during periods of sustained catecholamine secretion. In this report we
      demonstrate that when rats are subjected to short-term stress, TH mRNA is induced
      for at least 24 h, but TH protein and TH activity (assayed under Vmax conditions)
      are not increased. In contrast, adrenal TH mRNA, TH protein and TH activity are
      induced in rats subjected to long-term stress. Using sucrose gradient
      fractionation, we show that the lack of induction of TH protein after one type of
      short-term stressor, a single 2-h immobilization stress is associated with a
      decrease in the percentage of TH mRNA molecules associated with polysomes. In
      contrast, after repeated immobilizations the polysome profile of TH mRNA is
      identical to that observed in control animals, even though TH mRNA is induced 2-
      to 3-fold. These results are consistent with the hypothesis that even though TH
      mRNA is induced by short-term stressors, mechanisms that control TH mRNA
      translation must also be appropriately regulated for TH protein to be induced.

PMID- 17543900
TI  - Matrix metalloproteinase-3 and coronary remodelling: implications for unstable
      coronary disease.
AB  - OBJECTIVES: Matrix metalloproteinases (MMPs) are plausible candidates for
      prediction of unstable coronary syndromes. We hypothesised that the MMP-3
      polymorphism (- 1171, 5A/6A) would relate to coronary plaque characteristics and
      unstable clinical presentation. METHODS AND RESULTS: Forty patients with de novo
      presentation of coronary artery disease (CAD) were classified into unstable
      coronary syndrome (n=19) or stable angina pectoris (n=21). On coronary
      intravascular ultrasound, patients with unstable disease had a greater plaque
      burden, more positive (outward) coronary remodelling, and all but one were MMP-3
      6A allele carriers (p=0.027 compared with stable). The relationship between the
      6A allele and unstable presentation was substantiated in a validation cohort of
      161 CAD patients (58 stable and 103 unstable) and in the total population of 201
      CAD patients (79 stable and 122 unstable, p=0.007), and was independent of
      conventional risk factors. Furthermore, 6A allele carriers had a higher plasma
      MMP-3 concentration (15.8+/-12.5 versus 11.7+/-7.2 ng/mL, p=0.01), maximum
      coronary stenosis on angiography (89+/-15% versus 80+/-23%, p=0.02), plaque area
      (12.0+/-5.2 versus 7.5+/-3.6 mm(2), p=0.03), percentage plaque burden (82+/-7
      versus 71+/-13%, p=0.003), and remodelling ratio (1.03+/-0.23 versus 0.83+/-0.12,
      p=0.003). CONCLUSIONS: The MMP-3 6A allele promotes positive coronary
      remodelling, greater plaque burden, and increased susceptibility to unstable
      coronary syndromes in humans.

PMID- 17543901
TI  - Activation of PPARdelta inhibits cardiac fibroblast proliferation and the
      transdifferentiation into myofibroblasts.
AB  - OBJECTIVE: The development of heart failure is invariably associated with
      extensive fibrosis. Treatment with Peroxisome Proliferator-Activated Receptor
      (PPAR) ligands has been shown to attenuate cardiac fibrosis, but the molecular
      mechanism underlying this protective effect has remained largely unknown. In this
      study the potential of each PPAR isoform (PPARalpha, delta, and gamma) to
      attenuate cardiac fibroblast proliferation, fibroblast (CF) to myofibroblast
      (CMF) transdifferentiation, and collagen synthesis was investigated. METHODS AND
      RESULTS: PPARdelta was found to be the most abundant isoform in both CF and CMF.
      Only the PPARdelta ligand GW501516, but not PPARalpha ligand Wy-14,643 or
      PPARgamma ligand rosiglitazone, significantly increased PPAR-dependent promoter
      activity and expression of the PPAR-responsive gene UCP2 ( approximately 5-fold).
      GW501516 reduced the proliferation rate of CF (-38%) and CMF (-26%), which was
      associated with increased expression of the cell cycle inhibitor gene G0/G1
      switch gene 2 (G0S2). Exposure of CF to the PPARdelta ligand or adenoviral
      overexpression of PPARdelta significantly decreased alpha-smooth muscle actin
      (alpha-SMA) levels, indicating a reduced CF to CMF transition. The inhibition of
      transdifferentiation by PPARdelta correlated with an increase in PTEN
      (Phosphatase and Tensin Homolog Deleted on Chromosome ten) expression. (3)H
      Proline incorporation assays demonstrated a GW501516 induced decline in collagen
      synthesis (-36%) in CF. CONCLUSION: Cardiac fibroblast proliferation, fibroblast
      to myofibroblast differentiation and collagen synthesis were reduced after
      activation of PPARdelta, suggesting that PPARdelta represents an attractive
      molecular target for attenuating cardiac fibrosis.

PMID- 17543903
TI  - Language screening in the pediatric office setting.
AB  - This article discusses screening of language development in a pediatric office
      setting. It describes the relationship between language delay and various
      developmental disorders. It provides recent recommendations regarding the
      efficacy of formal language screening instruments, and suggests developmental
      guidelines for clinical observations. Referrals for specialty evaluations and
      services for evaluation and treatment are presented. The article offers
      suggestions for counseling parents when a language disorder is suspected.

PMID- 17543904
TI  - Language disorders in children: classification and clinical syndromes.
AB  - This article reviews the normal pattern of language development in infants and
      young children. Classifications of childhood language disorders are presented and
      common clinical syndromes are described. Etiologic and comorbid factors
      associated with the development of language disorder are discussed in relation to
      current understanding of genetic and neuroanatomic aspects of brain development.
      Finally, the long-term outcome of individuals with childhood-onset language
      disorders is discussed.

PMID- 17543905
TI  - Language disorders: autism and other pervasive developmental disorders.
AB  - This article summarizes current knowledge about language and communication
      impairments in children who have autism spectrum disorders. It reviews the
      language profiles that may be observed during the toddler and preschool years and
      in school-aged children and discusses receptive and expressive language skills
      that may be quite variable across the spectrum and the universal impairments in
      pragmatic aspects of language that are among the defining characteristics of the
      disorder. It concludes with clinical recommendations for pediatric screening of
      autism spectrum disorders and for continued monitoring of language difficulties
      in older children for whom interventions may be critical for enhancing effective
      communication in everyday life.

PMID- 17543906
TI  - Social communication impairments: pragmatics.
AB  - Social communication or pragmatic impairments are characterized and illustrated
      as involving inappropriate or ineffective use of language and gesture in social
      contexts. Three clinical vignettes illustrate different pragmatic impairments and
      the wealth of diagnostic information that can be garnered from observation of a
      child's social communication behavior. Definitions of, and developmental
      milestones in, domains of pragmatic competence are provided. Several screening
      instruments are suggested for use in assessing pragmatic competence within the
      time-frame of a pediatric examination. Frequent comorbid psychiatric conditions
      are described and a sample of current neurobiologic research is briefly
      summarized.

PMID- 17543907
TI  - Developmental dyslexia.
AB  - Reading skills progress in a stage-like manner. There is no evidence that
      reading, unlike language, develops without direct instruction. Failing to develop
      preceding skills has a dramatic impact on development of more sophisticated
      cognitive skills. For example, children who have poor phonemic sensitivity
      struggle to develop phonetic decoding; poor word recognition and word decoding
      skills have a negative impact on reading comprehension. Primary care physicians
      need to be aware of reading problems and frequent comorbid conditions.
      Recognition of risk factors can help physicians direct children early to badly
      needed resources, which, at the least, decreases the risk for and minimize the
      impact of one additional challenge for these children.

PMID- 17543908
TI  - Language impairment and psychiatric comorbidities.
AB  - This article provides an overview of language impairment and its associated
      conditions and discusses the interactive relationship between language and other
      domains of development, using the framework of developmental psychopathology.
      This framework emphasizes the mutually influential transactions approach between
      developmental domains within individuals and their environment. How knowledge can
      be translated to practice is discussed.

PMID- 17543909
TI  - Neuropsychology and genetics of speech, language, and literacy disorders.
AB  - The authors review the neuropsychology, brain bases, and genetics of three
      related disorders of language development: reading disability, or developmental
      dyslexia (RD); language impairment (LI); and speech sound disorder (SSD). Over
      the past three decades, cognitive analysis has demonstrated that the reading
      difficulties of most children who have RD result from phonologic impairments
      (difficulties processing the sound structure of language). Although understanding
      of LI and SSD is somewhat less developed, both disorders are also associated with
      phonologic impairments, which may account for their comorbidity with RD. Research
      across levels of analysis is progressing rapidly to promote understanding not
      only of each disorder by itself but also of the relationships of the three
      disorders to each other.

PMID- 17543910
TI  - Brain abnormalities in language disorders and in autism.
AB  - It has been speculated that autism and specific language impairment share common
      underlying neural substrates because of the overlap in language impairment issues
      and evidence suggesting parallels in other domains and implying a possible shared
      genetic risk. Anatomically the two sets of disorders have generally been studied
      using different methodologies, but when identical methodologies have been used
      substantial similarities have been noted. Functionally there is a growing body of
      literature suggesting sensory perception abnormalities that have parallels in
      both conditions and that may be upstream of language abnormalities. Finding
      upstream mechanisms that impact language and non-language abnormalities in autism
      and specific language impairment would impact the orientation taken by
      translational attempts to use science to design treatments.

PMID- 17543911
TI  - Using the language characteristics of clinical populations to understand normal
      language development.
AB  - The overall purpose of this article is to describe the speech and language
      abilities of children who have selected clinical conditions, not only to
      characterize the outcomes of those conditions, but also to understand fundamental
      requirements for language learning in typically developing children. This
      developmental cognitive neuroscience analysis conceptualizes the clinical
      conditions as naturalistic experimental manipulations, selectively altering
      factors in the language-learning situation that could not otherwise be ethically
      manipulated in a research study.

PMID- 17543912
TI  - Management of dyslexia, its rationale, and underlying neurobiology.
AB  - Developmental dyslexia is characterized by an unexpected difficulty in reading in
      children and adults who otherwise possess the intelligence and motivation
      considered necessary for accurate and fluent reading. Dyslexia is the most common
      and most carefully studied of the learning disabilities, affecting 80% of all
      individuals identified as learning disabled. Although in the past the diagnosis
      and implications of dyslexia were often uncertain, recent advances in the
      knowledge of the epidemiology, the neurobiology, the genetics, and the cognitive
      influences on the disorder now allow the disorder to be approached within the
      framework of a traditional medical model. This article reviews these advances and
      their implications for the approach to patients presenting with a possible
      reading disability.

PMID- 17543913
TI  - Early literacy interventions: reach out and read.
AB  - Linkages between literacy attainment and poverty have been well documented in the
      literature. This article reviews the literacy challenges for low-income children
      and the need for child health practitioners to be informed about children's
      literacy environments. The authors define literacy and emphasize that literacy is
      a continuous developmental process that includes listening, speaking, reading,
      and writing. Read Out and Read is a national model that has demonstrated its
      effectiveness to improve receptive and expressive language development in
      children. Pediatricians are uniquely positioned to address early child's literacy
      development because they are often the only practitioner regularly encountering
      parents, infants, and children during the preschool years.

PMID- 17543914
TI  - Cellular immune response to an engineered cell-based tumor vaccine at the
      vaccination site.
AB  - The engineered expression of the immune co-stimulatory molecules CD80 and CD137L
      on the surface of a neuroblastoma cell line converts this tumor into a cell-based
      cancer vaccine. The mechanism by which this vaccine activates the immune system
      was investigated by capturing and analyzing immune cells responding to the
      vaccine cell line embedded in a collagen matrix and injected subcutaneously. The
      vaccine induced a significant increase in the number of activated CD62L(-) CCR7(
      ) CD49b(+) CD8 effector memory T cells captured in the matrix. Importantly,
      vaccine responsive cells could be detected in the vaccine matrix within a matter
      of days as demonstrated by IFN-gamma production. The substitution of unmodified
      tumor cells for the vaccine during serial vaccination resulted in a significant
      decrease in activated T cells present in the matrix, indicating that immune
      responses at the vaccine site are a dynamic process that must be propagated by
      continued co-stimulation.

PMID- 17543915
TI  - On modeling of mutation probabilities.
AB  - A probability model is derived for DNA mutations and implemented in Java
      programming language to be accessible via Internet. Its time and space complexity
      is analyzed and optimized for a mutation probability matrix. Sample runs
      comparable to actual hereditary tests are presented. The implementation is useful
      for predicting mutations for laboratory use.

PMID- 17543928
TI  - Phytoextraction and phytoexcretion of Cd by the leaves of Tamarix smyrnensis
      growing on contaminated non-saline and saline soils.
AB  - Phytoremediation and more specifically phytoextraction, is an alternative
      restoration strategy for the clean up of heavy metal contaminated soils.
      Phytoextraction can only be successful if suitable plant species colonize the
      contaminated area, extract the toxic substances and accumulate them in their
      above ground tissues. In this study, the salt cedar Tamarix smyrnensis that is a
      widespread salt-tolerant plant in the Mediterranean region has been investigated.
      A pot experiment is conducted with T. smyrnensis grown in polluted soil with
      16ppm of cadmium and at three different salt concentrations (0.0, 0.5, 3.0% NaCl)
      for a 10-week period. It took place in an open-air area with natural light, at
      ambient temperature and humidity in an effort to keep the plants under conditions
      as similar as possible to those in the field. However, care was taken not to let
      them be rained on. Temperature ranged from 19 to 50 degrees C with 33 and 21
      degrees C being the average day and night temperature, respectively. Humidity
      ranged from 28% to 87% with a 13-14h photoperiod. The specific aims of this work
      are to investigate the accumulation of cadmium via root uptake at different
      saline conditions and cadmium excretion through salt glands on the surface of the
      leaves as a probable detoxification mechanism of the plant. Furthermore,
      measurements of chlorophyll content, biomass, and shoot length are used to
      evaluate the potential of the plant for the removal of cadmium from contaminated
      saline and non-saline soils. The experimental data suggest that increased soil
      salinity results in an increase of the cadmium uptake by T. smyrnensis. Analysis
      of white salt crystals taken from glandular tissue confirmed the fact that this
      plant excretes cadmium through its salt glands on the surface of the leaves as a
      possible detoxification mechanism in order to resist metal toxicity. Excreted
      cadmium is again released into the environment and it is redeposited on the top
      soil. Furthermore, increased salinity results in an increased excretion of the
      metal on Tamarix leaf surface. The presence of metals usually affects negatively
      the plant health, but T. smyrnensis developed no visible signs of metal toxicity,
      only salt toxicity symptoms were observed. Cadmium usually decreases the
      chlorophyll content in plants; however, the amount of photosynthetic pigments of
      T. smyrnensis was found not to be affected. All the above points to the potential
      of T. smyrnensis for use in phytoremediation with the metal secretion from the
      leaves being a unique advantage that may change current phytoextraction
      practices.

PMID- 17543939
TI  - Biochemical and pharmacological differences between preparations of exogenous
      natural surfactant used to treat Respiratory Distress Syndrome: role of the
      different components in an efficient pulmonary surfactant.
AB  - The pharmaceutical application of exogenous natural pulmonary surfactant
      preparations has shown its efficiency in the therapeutical treatment of infants
      with Respiratory Distress Syndrome. At the same time, the use of these
      preparations in patients with Acute Respiratory Distress Syndrome, although not
      still an effective therapy, shows promising results. The analysis of composition,
      structure and surface activity of some of the different natural surfactant
      preparations available today for clinical use reveals important differences, a
      fact that opens horizons in the optimization of new effective formulations in the
      treatment of the Acute Respiratory Distress Syndrome. The purpose of this review
      is to carry out an updating of the current models interpreting the role of the
      main components of pulmonary surfactant as a reference to evaluate the
      biochemical composition of the preparations of exogenous natural pulmonary
      surfactant currently in use and their apparent pharmacological effect.

PMID- 17543940
TI  - AQ4, an antitumor anthracenedione, inhibits endothelial cell proliferation and
      vascular endothelial growth factor secretion: implications for the therapy of
      ocular neovascular disorders.
AB  - Current clinical options for the treatment of neovascular disorders of the
      posterior segment of the eye have several drawbacks. Photocoagulation lasers can
      impair peripheral and night vision. Photodynamic therapies as well as
      intravitreal macromolecule injections (Macugen and Lucentis) require frequent,
      invasive administrations. Above all, only modest improvement in vision is
      achieved with any of the existing treatments. In order to overcome these
      limitations in the long run, this study investigated the antiangiogenic potential
      of AQ4, a low molecular weight anthracenedione. The results indicate that AQ4
      enters the cell nucleus and inhibits proliferation of choroid-retina endothelial
      (RF/6A) cells and human retinal pigment epithelial (ARPE-19) cells under hypoxic
      (1% O(2)) as well as normoxic (21% O(2)) conditions. The IC(50) for these effects
      ranges from 5.5 to 6.9 muM. AQ4 does not affect the viability of non-dividing
      RF/6A or ARPE-19 cells up to 0.1 mM. Further, AQ4 (20 muM) reduces vascular
      endothelial growth factor (VEGF) protein secretion by about 50% in ARPE-19 cells
      under normoxia as well as hypoxia, possibly by reducing VEGF transcription. AQ4
      arrests the growth of endothelial cells in S phase, consistent with interference
      of AQ4 with DNA replication. These results for the first time suggest that AQ4
      can potentially alleviate the neovascularization of choroid/retina by a dual
      mechanism of inhibiting the proliferation of endothelial cells and by reducing
      mitogenic VEGF stimulus from retinal pigment epithelial cells.

PMID- 17543941
TI  - Mice lacking cystathionine beta synthase have lung fibrosis and air space
      enlargement.
AB  - Cystathionine beta synthase (CBS) is a crucial regulator of plasma concentrations
      of homocysteine. Severe hyperhomocysteinemia due to CBS deficiency confers
      diverse clinical manifestations, notably pulmonary thrombotic disease. However,
      the association between hyperhomocysteinemia and chronic obstructive pulmonary
      disease is not well understood. To investigate the role of hyperhomocysteinemia
      in lung injury and pulmonary fibrosis, we analyzed the lung of CBS-deficient
      mice, a murine model of severe hyperhomocysteinemia. The degree of lung injury
      was assessed by histologic examination. Analysis of profibrogenic factors was
      performed by real-time quantitative reverse transcription-polymerase chain
      reaction. CBS-deficient mice develop fibrosis and air space enlargement in the
      lung, concomitant with an enhanced expression of heme oxygenase-1, pro(alpha)1
      collagen type I, transforming growth factor-beta1 and alpha-smooth muscle actin.
      However, lung fibrosis was found in the absence of increased inflammatory cell
      infiltrates as determined by histology, without changes in gene expression of
      proinflammatory cytokines TNFalpha and interleukin 6. The increased expression of
      alpha-smooth muscle actin and transforming growth factor-beta1 emphasizes the
      role of myofibroblasts differentiation in case of lung fibrosis due to CBS
      deficiency in mice.

PMID- 17543943
TI  - Race and disparities in health.

PMID- 17543944
TI  - Racial disparities in colorectal cancer.

PMID- 17543945
TI  - Disparities in breast cancer.

PMID- 17543946
TI  - Factors underlying disparities in cervical cancer incidence, screening, and
      treatment in the United States.

PMID- 17543947
TI  - Racial differences in the incidence and outcomes for patients with hematological
      malignancies.

PMID- 17543948
TI  - Racial disparities in lung cancer.

PMID- 17543949
TI  - Prostate cancer and race.

PMID- 17543950
TI  - Epidemiology of prostate cancer in Africa: another step in the understanding of
      the disease?

PMID- 17543952
TI  - Quantitative single particle tracking of NGF-receptor complexes: transport is
      bidirectional but biased by longer retrograde run lengths.
AB  - The retrograde transport of nerve growth factor (NGF) in neurite-like processes
      of living differentiated PC12 cells was studied using streptavidin-quantum dots
      (QDs) coupled to monobiotin-NGF. These reagents were active in differentiation,
      binding, internalization, and transport. Ten-35% of the QD-NGF-receptor complexes
      were mobile. Quantitative single particle tracking revealed a bidirectional step
      like motion, requiring intact microtubules, with a net retrograde velocity of
      0.054+/-0.020 microm/s. Individual runs had a mean velocity of approximately 0.15
      microm/s at room temperature, and the run times were exponentially distributed.
      The photostability and brightness of QDs permit extended real-time analysis of
      individual QDbNGF- receptor complexes trafficking within neurites.

PMID- 17543951
TI  - Parallel facilitatory reflex pathways from the foot and hip to flexors and
      extensors in the injured human spinal cord.
AB  - Spinal integration of sensory signals associated with hip position, muscle
      loading, and cutaneous sensation of the foot contributes to movement regulation.
      The exact interactive effects of these sensory signals under controlled dynamic
      conditions are unknown. The purpose of the present study was to establish the
      effects of combined plantar cutaneous afferent excitation and hip movement on the
      Hoffmann (H) and flexion reflexes in people with a spinal cord injury (SCI). The
      flexion and H-reflexes were elicited through stimulation of the right sural (at
      non-nociceptive levels) and posterior tibial nerves respectively. Reflex
      responses were recorded from the ipsilateral tibialis anterior (TA) (flexion
      reflex) and soleus (H-reflex) muscles. The plantar cutaneous afferents were
      stimulated at three times the perceptual threshold (200 Hz, 24-ms pulse train) at
      conditioning-test intervals that ranged from 3 to 90 ms. Sinusoidal movements
      were imposed to the right hip joint at 0.2 Hz with subjects supine. Control and
      conditioned reflexes were recorded as the hip moved in flexion and extension. Leg
      muscle activity and sagittal-plane joint torques were recorded. We found that
      excitation of plantar cutaneous afferents facilitated the soleus H-reflex and the
      long latency flexion reflex during hip extension. In contrast, the short latency
      flexion reflex was depressed by plantar cutaneous stimulation during hip flexion.
      Oscillatory joint forces were present during the transition phase of the hip
      movement from flexion to extension when stimuli were delivered during hip
      flexion. Hip-mediated input interacts with feedback from the foot sole to
      facilitate extensor and flexor reflex activity during the extension phase of
      movement. The interactive effects of these sensory signals may be a feature of
      impaired gait, but when they are appropriately excited, they may contribute to
      locomotion recovery in these patients.

PMID- 17543953
TI  - A soluble, magnesium-independent prenyltransferase catalyzes reverse and regular
      C-prenylations and O-prenylations of aromatic substrates.
AB  - Fnq26 from Streptomyces cinnamonensis DSM 1042 is a new member of the recently
      identified CloQ/Orf2 class of prenyltransferases. The enzyme was overexpressed in
      E. coli and purified to apparent homogeneity, resulting in a soluble, monomeric
      protein of 33.2 kDa. The catalytic activity of Fnq26 is independent of the
      presence of Mg(2+) or other divalent metal ions. With flaviolin (2,5,7-trihydroxy
      1,4-naphthoquinone) as substrate, Fnq26 catalyzes the formation of a carbon
      carbon-bond between C-3 (rather than C-1) of geranyl diphosphate and C-3 of
      flaviolin, i.e. an unusual "reverse" prenylation. With 1,3-dihydroxynaphthalene
      and 4-hydroxybenzoate as substrates Fnq26 catalyzes O-prenylations.

PMID- 17543954
TI  - Genome-wide screening of genes affecting glycogen metabolism in Escherichia coli
      K-12.
AB  - A systematic and comprehensive gene-disrupted mutant collection of E. coli K-12
      was used to identify genes whose deletions affect glycogen accumulation. Of the
      3985 non-essential gene mutants of the collection, 35 displayed a glycogen-excess
      phenotype, whereas 30 displayed either glycogen-less or glycogen-deficient
      phenotypes. The genes whose deletions affect glycogen accumulation were
      classified into various functional categories, including energy production,
      envelope composition and integrity, protein translation and stability, transport
      of inorganic ions and nucleotides, and metabolism of carbohydrates and amino
      acids. The overall data indicate that glycogen metabolism is highly
      interconnected with a wide variety of cellular processes in E. coli.

PMID- 17543955
TI  - Calpastatin simultaneously binds four calpains with different kinetic constants.
AB  - Calpastatin is the endogenous, specific protein inhibitor of the calcium
      dependent protease, calpain. Using an active site knock-out m-calpain mutant we
      have studied the enzyme's calcium-dependent binding to calpastatin by surface
      plasmon resonance without the complication of proteolysis. Calpastatin was
      capable of simultaneously binding four molecules of calpain. Its four inhibitory
      domains (CAST1, 2, 3, and 4) were individually expressed in Escherichia coli and
      the kinetics of their interaction with calpain was separately compared. Their
      K(d) values ranged from picomolar to nanomolar in the order CAST1>4>3>2. They
      have similar k(on) values but the k(off) values ranged over three orders of
      magnitude and can account for the differences in affinity.

PMID- 17543956
TI  - Anti-Mullerian hormone substance from follicular fluid is positively associated
      with success in oocyte fertilization during in vitro fertilization.
AB  - OBJECTIVE: To determine whether the anti-Mullerian hormone (AMH) level in
      follicular fluid is associated with success in oocyte fertilization during in
      vitro fertilization (IVF) cycles. DESIGN: Retrospective study. SETTING: Tokyo
      Medical University hospital. PATIENT(S): Thirty-one women undergoing IVF cycles.
      INTERVENTION(S): The women were divided into two groups according to the success
      or failure of fertilization. Follicular fluid samples were obtained from a single
      follicle in each patient. MAIN OUTCOME MEASURE(S): Assessment of values for AMH,
      inhibin B, and estradiol from follicular fluid and serum on the day of oocyte
      retrieval during IVF treatment. RESULT(S): The follicular fluid AMH levels from
      fertilized patients (group 1) were 3.42 times higher than from nonfertilized
      (group 2). There was no correlation between the ratio of the high quality grade
      embryos and either serum AMH or inhibin B levels. There was no statistically
      significant correlation between serum AMH and the number of oocytes. However,
      there was a strong correlation between levels of serum estradiol, inhibin B, and
      the number of oocytes. CONCLUSION(S): Oocytes are more likely to be fertilized
      when follicles are able to make high concentrations of AMH in the follicular
      fluid. Thus, AMH could be a prediction marker for fertilization.

PMID- 17543957
TI  - Combining ovarian tissue cryobanking with retrieval of immature oocytes followed
      by in vitro maturation and vitrification: an additional strategy of fertility
      preservation.
AB  - OBJECTIVE: To report an additional strategy of fertility preservation, which
      combines ovarian tissue cryobanking with retrieval of immature oocytes from
      excised ovarian tissue, followed by in vitro maturation (IVM) and vitrification.
      DESIGN: Retrospective analysis of case series. SETTING: University teaching
      hospital. PATIENT(S): Women who underwent oophorectomy or ovarian wedge resection
      before receiving chemotherapy and/or radiotherapy. INTERVENTION(S): Immature
      oocyte retrieval, IVM, oocyte vitrification, ovarian tissue cryobanking. MAIN
      OUTCOME MEASURE(S): Oocytes retrieved from the excised ovarian tissue, oocyte
      maturation rate, and number of oocytes cryopreserved by vitrification. RESULT(S):
      Four consecutive patients underwent retrieval of immature oocytes from the antral
      follicles of the excised ovarian tissue. The mean number of immature oocytes
      recovered was three (1, 3, 4, and 3, respectively). The mean maturation rate
      following IVM was 79% (100%, 100%, 50%, and 67%, respectively). In total, eight
      mature oocytes were vitrified. CONCLUSION(S): Oocytes can be retrieved from
      excised ovarian tissue, matured in vitro, and cryopreserved by vitrification.
      This fertility preservation technique could be combined with ovarian tissue
      cryobanking.

PMID- 17543958
TI  - Alteration of focal adhesion kinase expression in eutopic endometrium of women
      with endometriosis.
AB  - OBJECTIVE: To investigate whether focal adhesion kinase (FAK) expression is
      altered in eutopic endometrium of women with endometriosis. DESIGN: Experimental
      study using human endometrial tissue. SETTING: Academic research center.
      PATIENT(S): Women with or without endometriosis who were undergoing surgery for
      benign indications. INTERVENTION(S): Endometrial biopsy. MAIN OUTCOME MEASURE(S):
      Expression of FAK was assessed by immunohistochemistry, Western blotting
      analysis, and reverse-transcription polymerase chain reaction. RESULT(S): At
      secretory phase, the average level of endometrial FAK expression of women with
      endometriosis was significantly higher than that of controls, but no significant
      difference was found between the two groups at proliferative phase. There was a
      positive correlation between FAK expression in secretory endometrial tissues and
      disease stage and pelvic pain in women with endometriosis. Furthermore, the
      endometrial FAK protein expression varied with the serum E(2) at proliferative
      phase and with the ratio of E(2) to P at secretory phase. CONCLUSION(S): The
      study showed a significant increase of FAK expression in the secretory
      endometrial tissues of women with endometriosis, a relationship between FAK
      expression and disease stage, pelvic pain, and serum steroid hormones. Those
      results suggest that FAK may play a role in the pathogenesis of endometriosis and
      be regulated by steroid hormones.

PMID- 17543959
TI  - Serotonin 1A receptor reductions in postpartum depression: a positron emission
      tomography study.
AB  - OBJECTIVE: To measure brain serotonin-1A (5HT1A) receptor binding potential (BP)
      in healthy and depressed postpartum women. DESIGN: 5HT1A receptor BP was measured
      with positron emission tomography by using [(11)C]WAY100635 a single time.
      Multivariate analysis of variance was used to determine depression effects on
      5HT1A receptor BP in relevant brain regions. SETTING: An academic research
      environment. PATIENT(S): Seven postpartum healthy controls and nine postpartum
      depressed (PD) subjects with perinatal (antepartum or postpartum) depression
      onset. Of the nine PD subjects, five had unipolar depression, and four had
      bipolar disorder. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): 5HT1A receptor
      BP. RESULT(S): Age, time since delivery, and reproductive hormones did not differ
      between groups. Postsynaptic 5HT1A receptor binding in postpartum depression was
      reduced 20%-28% relative to controls, with most significant reductions in
      anterior cingulate and mesiotemporal cortices. CONCLUSION(S): Postsynaptic 5HT1A
      receptor binding is reduced in PD women by a similar magnitude as has been shown
      in other depression samples. The postpartum hormonal milieu and the large
      proportion of bipolar spectrum subjects in the PD group may have accentuated this
      finding in this small sample. Recognition of this neurobiological deficit in
      postpartum depression may be useful in the development of treatments and
      prevention strategies for this disabling disorder.

PMID- 17543960
TI  - Proportional change of CD4+CD25+ regulatory T cells in decidua and peripheral
      blood in unexplained recurrent spontaneous abortion patients.
AB  - OBJECTIVE: To investigate the proportional changes of CD4(+)CD25(+) regulatory T
      cells in peripheral blood and decidua in unexplained recurrent spontaneous
      abortion (URSA) and normal pregnant (NP) women. DESIGN: Prospective, case-control
      study. SETTING: Large public hospital in a major city in China. PATIENT(S):
      Twenty-five URSA patients and 34 normal, early pregnant, control women.
      INTERVENTION(S): Measurements of CD4(+)CD25(+) regulatory T cells in decidua and
      peripheral blood. MAIN OUTCOME MEASURE(S): The proportion of CD4(+)CD25(bright)
      regulatory T cells; the percentage of CD25(bright) cells in the CD4(+) T-cell
      population. RESULT(S): The proportions of CD4(+)CD25(bright) T cells in both
      decidua and peripheral blood in URSA patients were statistically significantly
      lower than those in control women. Meanwhile, the percentage of CD25(bright)
      cells in the CD4(+) T-cell population in decidua was statistically significantly
      lower in URSA patients than in control women. The percentage of CD25(bright)
      cells in the CD4(+) T-cell population in decidua was statistically significantly
      higher than that in peripheral blood in control women, whereas the difference was
      not significant in patients who have URSA. CONCLUSION(S): Human
      CD4(+)CD25(bright) T cells play a major role in tolerating conceptus antigens and
      therefore may contribute to the maintenance of pregnancy. The data suggest that
      CD4(+)CD25(+) regulatory T cells may be a novel target in URSA therapy.

PMID- 17543961
TI  - Prevalence of the metabolic syndrome and its components in Brazilian women with
      polycystic ovary syndrome.
AB  - OBJECTIVE: To determine the prevalence of the metabolic syndrome (MetS) and its
      components in Brazilian women with polycystic ovary syndrome (PCOS). DESIGN:
      Cross-sectional study. SETTING: University Hospital, Federal University of Rio
      Grande do Norte, Natal-RN, Brazil. PATIENT(S): 102 women with PCOS by the
      Rotterdam consensus criteria. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S):
      Clinical and biochemical parameters for MetS as defined by the National
      Cholesterol Education Program Adult Treatment Panel (NCEP ATP III). RESULT(S):
      The prevalence for individual components of MetS were high-density lipoprotein
      cholesterol level <50 mg/dL in 69.6%, waist circumference >or=88 cm in 57.9%,
      triglyceride level >or=150 mg/dL in 31.7%, blood pressure >or=130/85 mm Hg in
      18.6%, and fasting glucose concentrations >or=110 mg/dL in 2.9%. Three or more of
      these individual criteria were present in 29 (28.4%) of the patients. The
      prevalence of MetS increased with body mass index: 3.2%, 19.2% and 52.3% for
      normal, overweight, and obese women, respectively. CONCLUSION(S): These findings
      indicate that Brazilian women with PCOS have a high prevalence of MetS and its
      individual components, particularly a decreased high-density lipoprotein
      cholesterol level. Thus, these women are at increased risk of diabetes mellitus
      and cardiovascular disease.

PMID- 17543962
TI  - Testicular adrenal rest tumors in patients with congenital adrenal hyperplasia
      can cause severe testicular damage.
AB  - OBJECTIVE: To evaluate the histological features of testicular tumors and
      residual testicular parenchyma in male patients with congenital adrenal
      hyperplasia (CAH) and longstanding bilateral testicular adrenal rest tumors
      (TART). DESIGN: Descriptive study. SETTING: University medical center in the
      Netherlands. PATIENT(S): Seven male patients who had CAH with longstanding
      bilateral TART and who were treated with testis-sparing surgery. INTERVENTION(S):
      Enucleation of TART and taking biopsies of the surrounding testicular parenchyma.
      MAIN OUTCOME MEASURE(S): Description of the histological features of TART and
      residual testicular parenchyma. RESULT(S): All tumors had a similar histological
      appearance, with sheets of polygonal cells separated by dense fibrous tissue with
      focal lymphocytic infiltrates and without Reinke crystals. All biopsies showed a
      decrease in tubular diameter with peritubular fibrosis and, in four patients,
      tubular hyalinization. The germinative layer showed decreased spermatogenesis and
      reduced Johnsen scores. CONCLUSION(S): Testicular adrenal rest tumors can lead to
      end-stage damage of testicular parenchyma, most probably as a result of
      longstanding obstruction of the seminiferous tubules. Therefore, treatment at an
      early stage is advised.

PMID- 17543963
TI  - Pregnancy after Essure placement: report of two cases.
AB  - OBJECTIVE: To report two cases of pregnancy after placement of Essure micro
      inserts. DESIGN: Case report. SETTING: University-based Department of Obstetrics
      and Gynecology. PATIENT(S): Patient 1, a 38-year-old woman, presented with a
      positive pregnancy test 7 months after Essure hysteroscopic sterilization.
      Patient 2, a 35-year-old female, became pregnant approximately 1 year after
      undergoing the Essure procedure. INTERVENTION(S): Patient 1 received obstetric
      ultrasounds, a prophylactic cerclage, a cesarean section, and a tubal ligation.
      Patient 2 underwent a postprocedure hysterosalpingogram, an obstetric ultrasound,
      pregnancy termination, diagnostic pelvic ultrasound, and a hysterectomy. MAIN
      OUTCOME MEASURE(S): Documentation of normal progress of pregnancy after Essure
      placement. RESULT(S): Patient 1 carried an uncomplicated pregnancy to term with
      an Essure micro-insert in place. Patient 2 became pregnant despite an
      hysterosalpingogram showing tubal occlusion and was ultimately found to have a
      micro-insert perforating the uterine wall. CONCLUSION(S): The presence of Essure
      micro-inserts in the fallopian tubes do not appear to interfere with implantation
      and pregnancy. Uterine perforation by an Essure micro-insert in proximity to the
      tubal ostia may mimic proper micro-insert placement and bilateral tubal occlusion
      on both hysterosalpingogram and saline infusion sonography.

PMID- 17543964
TI  - Expression of sex steroid hormone-related genes in the embryo of the leopard
      gecko.
AB  - Sex steroid hormones are known to play a central role in vertebrate sex
      determination and differentiation. However, the tissues in which they are
      produced or received during development, especially around the period of sex
      determination of the gonads, have rarely been investigated. In this study, we
      identified the cDNA sequence, including the full-length of the coding region of
      cholesterol side-chain cleavage enzyme (P450scc), from the leopard gecko; a
      lizard with temperature-dependent sex determination. Embryonic expression
      analysis of two steroidogenic enzymes, P450scc and P450 aromatase (P450arom), and
      four sex steroid hormone receptors, androgen receptor, estrogen receptor alpha
      and beta, and progesterone receptor, was subsequently conducted. mRNA expression
      of both steroidogenic enzymes was observed in the brain and gonads prior to the
      temperature-sensitive period of sex determination. The mRNAs of the four sex
      steroid hormone receptors were also detected in the brain and gonads at all
      stages examined. These results suggest the existence of a gonad-independent sex
      steroid hormone signaling system in the developing leopard gecko brain.

PMID- 17543967
TI  - Re: The use of regional anaesthesia in patients at risk of acute compartment
      syndrome.

PMID- 17543968
TI  - Surgical management of neglected fractures of the patella.
AB  - Between April 1996 and May 2002, 22 people (18 men, 4 women) were treated for
      neglected fractures of the patella at our hospital. The median patient age was 43
      (range 22-55) years. The majority of the fractures were caused by a direct fall
      on the knee. In all they comprised 18 transverse, 2 comminuted and 2 lower pole
      fractures, most of which had been treated by traditional methods initially. The
      median time between injury and surgery was 3 (range 2-6.5) months. Treatment
      methods in the orthopaedic department included tension band wiring in 16 cases,
      tension band wiring with cerclage in 3 cases and patellectomy in 3 cases. Results
      were evaluated after a median follow-up period of 5.5 (range 2-9) years and were
      based on Bostman criteria. Excellent results were achieved in 5 and good results
      in 15 cases. The poor results in two cases were due to infection and implant
      failure. Surgical treatment of neglected fractures of patella can thus lead to
      favourable outcomes.

PMID- 17543970
TI  - Interaction of mechanics and biology in knee joint restoration and regeneration.
      From cells to limbs--multi-scale approaches for clinical applications. Berlin, 28
      30 June 2006.

PMID- 17543969
TI  - The amastigote forms of Leishmania are experts at exploiting host cell processes
      to establish infection and persist.
AB  - Leishmania are dimorphic protozoan parasites that live as flagellated forms in
      the gut of their sandfly vector and as aflagellated forms in their mammalian
      hosts. Although both parasite forms can infect macrophages and dendritic cells,
      they elicit distinct responses from mammalian cells. Amastigotes are the
      parasites forms that persist in the infected host; they infect cells recruited to
      lesions and disseminate the infection to secondary sites. In this review I
      discuss studies that have investigated the mechanisms that Leishmania amastigotes
      employ to harness the host cell's response to infection. It should be
      acknowledged that our understanding of the mechanisms deployed by Leishmania
      amastigotes to modulate the host cell's response to infection is still
      rudimentary. Nonetheless, the results show that amastigote interactions with
      mammalian cells promote the production of anti-inflammatory cytokines such as IL
      10 and TGF-beta while suppressing the production of IL-12, superoxide and nitric
      oxide. An underlying issue that is considered is how these parasites that reside
      in sequestered vacuolar compartments target host cell processes in the cytosol or
      the nucleus; does this occur through the release of parasite molecules from
      parasitophorous vacuoles or by engaging and sustaining signalling pathways
      throughout the course of infection?

PMID- 17543971
TI  - Analysis of nucleotides by pressure-assisted capillary electrophoresis-mass
      spectrometry using silanol mask technique.
AB  - A method for the determination of nucleotides based on pressure-assisted
      capillary electrophoresis-electrospray ionization mass spectrometry (PACE-MS) is
      described. To prevent multi-phosphorylated species from adsorbing onto the fused
      silica capillary, silanol groups were masked with phosphate ions by
      preconditioning the capillary with the background electrolyte containing
      phosphate. During preconditioning, nebulizer gas was turned off to avoid
      contamination of MS detector with phosphate ions. To detect nucleotides using the
      CE positive mode at a pH 7.5, it was necessary to apply air pressure to the inlet
      capillary during electrophoresis to supplement the electroosmotic flow (EOF)
      toward the cathode. Moreover, we exchanged the running electrolyte every analysis
      using the buffer replenishment system to obtain the required reproducibility.
      Under the optimized conditions, 14 phosphorylated species such as nucleotides,
      nicotinamide-adenine dinucleotides and coenzyme A (CoA) compounds were well
      determined in less than 20 min. The relative standard deviations (n=6) of the
      method were better than 0.9% for migration times and between 1.7% and 8.1% for
      peak areas. The detection limits for these species were between 0.5 and 1.7
      micromol/L with pressure injection of 50 mbar for 30 s (30 nL) at a signal-to
      noise ratio of 3. This approach is robust and quantitative compared to the
      previous method, and its utility is demonstrated by the analysis of intracellular
      nucleotides and CoA compounds extracted from Escherichia coli wild type, pfkA and
      pfkB knockout mutants. The methodology was used to suggest that pfkA is the main
      functional enzyme.

PMID- 17543972
TI  - Use of gas chromatography-mass spectrometry for identification of a new
      disaccharide in honey.
AB  - Gas chromatography-mass spectrometry has been used to separate and identify
      disaccharides of edible honey. According to the characteristic fragmentation
      behaviour of disaccharide TMS-oximes, fructofuranosyl-(2-1)-fructose (inulobiose)
      has been structurally characterized. Identification was carried out on the basis
      of retention time on two columns of different polarity and mass spectrometric
      analysis. Inulobiose was found in honeys of different origins for the first time,
      varying within 0.93 and 6.14 mg/g of honey. Its occurrence in honeys is
      discussed.

PMID- 17543973
TI  - Extraction and ultra-performance liquid chromatography of hydrophilic and
      lipophilic bioactive components in a Chinese herb Radix Salviae Miltiorrhizae.
AB  - An ultra-performance liquid chromatography (UPLC) method has been developed and
      validated for the quality evaluation of a Chinese herb Radix Salviae
      Miltiorrhizae (Danshen root) by chemical fingerprinting analysis. Meanwhile a
      novel sample preparation procedure has been designed which can simultaneously
      extract both the hydrophilic and lipophilic components for a single run LC
      system. Comparing to the conventional HPLC method, UPLC showed many advantages
      including reduced run time, less solvent consumption and increased peak
      capacities. Using the established method, 20 target components were detected
      based on the retention times and on-line UV spectra by referencing to the
      available standards and reported data. Eleven crude drug samples from different
      sources were evaluated using the UPLC fingerprints. The developed method proved
      practicable and reliable for quality control of herbal products with multivalent
      components in a complicated matrix.

PMID- 17543974
TI  - Inverse gas chromatographic investigation of the active sites related to CO
      adsorption over Rh/SiO2 catalysts in excess of hydrogen.
AB  - In the present work, the novel methodology of reversed-flow gas chromatography
      (RF-GC) is extended in a topic of contemporary scientific and technological
      interest, such as the effect of hydrogen in the "topography" of the active sites
      related to CO adsorption. This study concerns CO adsorption on a silica-supported
      Rh catalyst, at 90 degrees C. The topography of the catalyst in the absence of
      hydrogen consists of both randomly and islands of CO bound over chemisorbed CO
      molecules. In contrast, under H2-rich conditions, the observed topography is
      almost entirely patchwise ascribed to long-range lateral attractions between
      adsorbate molecules. In excess of hydrogen, CO adsorption is shifted at higher
      lateral attractions values which correspond to weaker adsorbate-adsorbent
      interactions and lower surface coverage. This provides an indication of a H2
      induced desorption, which can be attributed to the formation of an H-CO complex
      desorbing from the catalyst surface below the temperature required for CO
      desorption, in the absence of H2, and it may explain the well-known enhancement
      of the rate of selective CO oxidation in excess of hydrogen by H2.

PMID- 17543975
TI  - Nonaqueous electrokinetic chromatography-electrospray ionization mass
      spectrometry using anionic cyclodextrins.
AB  - The set-up of an on-line method for coupling nonaqueous electrokinetic
      chromatography (NAEKC) and electrospray ionization mass spectrometry (ESI-MS) is
      presented. It allows the use of the single-isomer derivative anionic
      cyclodextrins heptakis(2,3-di-O-methyl-6-O-sulfo)-beta-cyclodextrin (HDMS-beta
      CD) and heptakis(2,3-di-O-acetyl-6-O-sulfo)-beta-cyclodextrin (HDAS-beta-CD) for
      chiral and achiral separations of positively charged analytes. The effect of the
      cyclodextrins (CDs) on the MS signal intensities of model compounds was studied.
      When a voltage is applied over the CE capillary, the overall mobility of the CDs
      is towards the inlet vial preventing CDs from entering the ion source. However,
      the sodium counter ions of the CDs still enter the ion source and appeared to
      cause ionization suppression. Nevertheless, significant analyte signals could
      still be detected with detection limits in the sub-microg/ml. System parameters
      such as sheath liquid composition and flow rate, nebulizing gas pressure,
      capillary position in the sprayer and the drying gas flow and temperature were
      studied and optimized. The selection of a relatively low nebulizing gas pressure
      appeared to be important to achieve optimum sensitivity. The chiral selectivity
      of the NAEKC-ESI-MS system could be improved by addition of camphorsulfonate to
      the background electrolyte. Using mixtures of drugs and drug-related compounds,
      the NAEKC-ESI-MS system is shown to offer potential for (chiral) drug profiling.

PMID- 17543976
TI  - Surfactant-aided size-exclusion chromatography for the purification of
      immunoglobulin G.
AB  - In the production of monoclonal antibodies, separate chains of the antibody are
      often present in the product mixture as well as other contaminating proteins.
      These fragments should be removed from the whole antibodies. This paper shows the
      purification of monoclonal immunoglobulin G (IgG) from its heavy chain
      contaminant. The heavy chain fragment is simulated experimentally using bovine
      serum albumin (BSA), which has approximately the same molecular weight. The
      purification is performed using traditional size-exclusion chromatography (SEC)
      and using surfactant-aided SEC (SASEC), testing two different surfactants
      (C(12)E(23) and Tween20) and two different gels (Sephacryl S200HR and Sephacryl
      S300 HR). Pulse experiments show that with SASEC both BSA and IgG are more
      distributed towards the solid phase than compared to using SEC. This effect is
      larger on IgG, the largest component than on BSA. As a consequence, azeotropes
      will be formed at a specific surfactant concentration. Above this concentration
      the selectivity is reversed and increased to values higher than obtained with
      conventional SEC. At 7.5% (w/w) of C(12)E(23), BSA actually elutes before IgG.
      These experiments further show that when using SASEC larger productivity, higher
      yields and lower solvent consumption can be achieved without loss of purity of
      IgG when compared to conventional SEC. Mathematical simulation of the separation
      of BSA and IgG using simulated moving bed (SMB) chromatography indicates a large
      increase in productivity when applying a surfactant gradient in SASEC SMB
      compared to conventional isocratic SEC-SMB. Furthermore, solvent consumption
      reductions with a factor 15 prove possible as well as concentrating the IgG by a
      factor 2.

PMID- 17543977
TI  - Analyses of gibberellins by capillary electrophoresis-mass spectrometry combined
      with solid-phase extraction.
AB  - A new, simple and rapid capillary electrophoresis-mass spectrometry (CE-MS)
      method, using a cationic polymer-coated capillary to reverse electroosmotic flow,
      is proposed and validated for the separation and simultaneous quantification of
      11 gibberellins (GAs). Under optimum conditions, a baseline separation of 11 GAs,
      including GA1, GA3, GA4, GA5, GA6, GA7, GA13, GA19, GA20, GA24 and GA53 was
      accomplished within 25 min using 70 mM ammonium formate/formic acid buffer (pH
      3.8) and 2% (v/v) acetonitrile with -25 kV as the separation voltage.
      Satisfactory results were obtained in terms of linearity (R2 between 0.984 and
      0.995), precision (RSD of migration time below 0.8%) and sensitivity (LOD between
      0.31 and 1.02 microM). Furthermore, a novel solid-phase extraction (SPE)
      procedure was developed for the pre-concentration and purification of GAs using
      Oasis MAX cartridges. The combination of SPE and CE-MS approach was applied to
      screen for endogenous GAs present in coconut (Cocos nucifera L.) water sample. To
      illustrate the applicability of the method, GA1 and GA3 were successfully
      detected and quantified in coconut water. Finally, the GA1 and GA3 identities
      were further unequivocally confirmed by CE-tandem MS experiments operating in the
      multiple reaction monitoring mode.

PMID- 17543978
TI  - Electrophoretically mediated microanalysis of a nicotinamide adenine dinucleotide
      dependent enzyme and its facile multiplexing using an active pixel sensor UV
      detector.
AB  - An electrophoretically mediated microanalysis (EMMA) method has been developed
      for yeast alcohol dehydrogenase and quantification of reactant and product
      cofactors, NAD and NADH. The enzyme substrate ethanol (1% (v/v)) was added to the
      buffer (50 mM borate, pH 8.8). Results are presented for parallel capillary
      electrophoresis with a novel miniature UV area detector, with an active pixel
      sensor imaging an array of two or six parallel capillaries connected via a
      manifold to a single output capillary in a commercial CE instrument, allowing
      conversions with five different yeast alcohol dehydrogenase concentrations to be
      quantified in a single experiment.

PMID- 17543979
TI  - Improving immunobinding using oriented immobilization of an oxidized antibody.
AB  - Recent technical advances in biorecognition engineering and microparticle
      fabrication enabled us to develop a single-step purification process using
      magnetic particles (MPs). The process is simple, efficacious, easy to automate,
      and economical. The method immobilizes the ligand molecule in a particular
      orientation on commercial MPs that have surface carboxyl groups. Mouse IgG and
      anti-mouse IgG antibody were the model capture and ligand molecules for this
      study. The immunobinding efficacy of anti-mouse IgG antibody using "oriented
      immobilization" was compared with the efficacy of a conventional amine-coupling
      system that results in random orientation and of another standard method, the
      biotin-streptavidin system. The oriented immobilization was accomplished by
      oxidizing the sugar moiety in the CH(2) domain of the antibody's Fc and
      covalently conjugating the moiety to the hydrazine-coated MP. The specific
      binding affinity of the oriented immobilization process was about 2.5 times that
      of the amine-coupling system, and selectivity from a binary mixture was about 2
      times greater for the oriented immobilization method. Results were nearly
      identical for the biotin-streptavidin system and the oriented immobilization
      system, matching the calculated binding stoichiometry between mouse IgG and anti
      mouse IgG antibody. The binding improvement over the amine-coupling system shown
      by assay was confirmed by a separate surface plasmon resonance experiment. In
      summary, the oriented immobilization method was as effective as the streptavidin
      biotin system, yet simpler and cost-effective.

PMID- 17543980
TI  - Factor analysis of hyphenated chromatographic data exploration, resolution and
      quantification of multicomponent systems.
AB  - Factor analysis (FA) is a family of widely used methods to obtain the underlying
      sources of variation of data tables. Typically, hyphenated chromatographic data
      provide data tables with one elution direction and another linked to the detector
      response. In this context, the factors are the eluting compounds and the profiles
      defining each factor are the elution profile and the pure response of the
      compound. This article describes the use of FA in chromatography through diverse
      tools and problems. Examples of determination of number of compounds, peak purity
      problems, resolution of overlapped compounds or extension to simultaneous
      analysis of multiple runs (higher-order data structures) to obtain qualitative
      and quantitative information are reviewed.

PMID- 17543981
TI  - Aliphatic carboxylic acids as new modifiers for separation of 2,4-dinitrophenyl
      amino acids by micellar liquid chromatography.
AB  - The possibilities of isocratic separation of 2,4-dinitrophenyl derivatives of 12
      amino acids that considerably differ in hydrophobicity by micellar mobile phases
      with different organic modifiers have been discussed. For the first time
      aliphatic carboxylic acids have been used as modifiers of micellar eluent in
      micellar liquid chromatography with C18 columns. Elution strength of hybrid
      micellar phases on the basis of sodium dodecylsulfate and aliphatic carboxylic
      acids increases in sequence: acetic<propanoic<butanoic<pentanoic<hexanoic acid.
      The effect of sodium dodecylsulfate micelles on aliphatic carboxylic acids has
      been characterized by their micellar-induced shifts of ionization constants. The
      use of aliphatic carboxylic acids as modifiers of SDS micellar eluents provides
      better overall resolution of 2,4-dinitrophenyl-amino acids in comparison with
      aliphatic alcohols.

PMID- 17543982
TI  - Effect of surfactant structure on the residual fluorescence of micelle-based
      fluorescent probes.
AB  - In the present paper we have investigated some photo-physical characteristics of
      different micellar-based fluorescent probes containing a fluorophore (pyrene) and
      a quencher unit (dodecyl-dioxo 2,3,2). The fluorescent response of the probe in
      the presence of Cu(II) ions was studied using different micellar substrates, and
      it was found that the pH at which the On-Off jump occurs is not influenced by the
      chemical structure of surfactant. In addition, the experimental residual
      fluorescence is not proportionally affected by microviscosity or by the size of
      the micellar aggregates. The signal of the native fluorescence of pyrene was
      observed even when the quencher's occupancy number was greater than one.
      Moreover, we observed discrepancies between experimental values and calculated
      residual fluorescence using Laplace data. These results were interpreted
      suggesting that the residual fluorescence has two main components, one that seems
      to be independent on micellar properties, while the other is directly related to
      location of molecules inside the surfactant aggregates that serve as substrate.

PMID- 17543983
TI  - Structure of water in the vicinity of amphoteric polymers as revealed by Raman
      spectroscopy.
AB  - The structure and hydrogen bonding of water in an aqueous solution of amphoteric
      copolymers (poly(MA-r-DMAPMA), 3x10(3)<M(w)<10(4)) composed of various ratios of
      methacrylic acid (MA) and N-[3-(dimethylamino)propyl]methacrylamide (DMAPMA) were
      analyzed using the band shapes of the OH stretching in the polarized Raman
      spectra. The number of hydrogen bonds disrupted due to the presence of one
      monomer residue (N(corr) value) evaluated for poly(methacrylic acid) was largely
      positive, and with an increase in the content of the DMAPMA residue, the N(corr)
      value became smaller, and after passing a minimum (which was still slightly
      positive) at a roughly equivalent molar ratio (P(M(47)D(53)); M, methacrylic
      acid; D, N-[3-(dimethylamino)propyl]methacrylamide), increased again. This is in
      a significant contrast with the largely positive N(corr) values for the
      homopolymers of MA and DMAPMA, and other ordinary polyelectrolytes. The small
      N(corr) value for P(M(47)D(53)) was comparable to those for water-soluble
      nonionic polymers such as poly(ethylene glycol) and zwitterionic polymers such as
      polycarboxybetaine. These results suggested that the balance of electric charges
      in polymeric materials is important to be inert to the structure of vicinal
      water.

PMID- 17543984
TI  - Influence of pollen quality on ovarian development in honeybee workers (Apis
      mellifera scutellata).
AB  - Protein-rich diets are known to promote ovarian and egg development in workers of
      the honeybee, Apis mellifera, even in the presence of a queen. Since the main
      source of protein for honeybees is pollen, its quality and digestibility might be
      important dietary factors determining reproductive capacity. We have compared the
      effect of two types of pollen-sunflower, Helianthus annuus, and aloe, Aloe
      greatheadii var davyana-on ovarian development in A. mellifera scutellata
      workers. Under queenright conditions in the field, worker bees exhibited greater
      ovarian development when feeding on aloe pollen than on sunflower pollen. In
      their midgut, we observed higher extraction efficiency for aloe (80%) than for
      sunflower (69%) pollen. This may be attributed to the morphology and size of the
      two kinds of pollen grains and explains, together with the high protein content
      of aloe pollen (32% dry mass in bee-collected pollen) compared to sunflower
      pollen (15%), why aloe pollen promoted higher ovarian development. However, in
      the laboratory workers sustained on aloe pollen had significantly less-developed
      ovaries and higher mortality than those fed sunflower pollen. These detrimental
      effects may be due to an unbalanced protein:carbohydrate ratio. We discuss the
      effects of unbalanced diets on the physiology and ecology of honeybee
      reproduction.

PMID- 17543985
TI  - Differential effects of phosphorylation on DNA binding properties of N Oct-3 are
      dictated by protein/DNA complex structures.
AB  - N Oct-3, a transcription factor member of the POU protein family, is implicated
      in normal central nervous system development but also in melanoma growth. Its DNA
      binding domain (DBD) comprises two subdomains, POUs and POUh, joined by a linker
      peptide. We have previously shown that N Oct-3 can interact with the already
      described PORE and MORE DNA motifs, but also with a new structural element we
      have termed NORE. Having observed that both the PORE and NORE DNA-association
      modes depend on a strong anchoring of the POUh subdomain rigid arm into the DNA
      target minor groove, in contrast to the MORE mode, we have formulated the
      hypothesis that phosphorylation of the conserved Ser101 residue located in the N
      Oct-3 POUh arm could lead to differential results in DNA binding according to the
      type of target. Here we demonstrate that, in vitro, Ser101 is phosphorylated by
      protein kinase A (PKA), either purified or contained in melanoma (624 mel)
      nuclear extract, and that this phosphorylation indeed significantly reduced N Oct
      3 DBD binding to PORE and NORE motifs, most likely by hampering the POUh rigid
      arm insertion in the DNA minor groove. Conversely, no effect was observed on the
      binding of N Oct-3 DBD to MORE sequences. Finally, once bound to its DNA targets,
      N Oct-3 DBD is less susceptible to PKA activity. We conclude that transcription
      of genes exhibiting a MORE motif in their promoter should be less affected by N
      Oct-3 phosphorylation than that of genes switched on by PORE or NORE sequences.

PMID- 17543986
TI  - Structural analysis of lac repressor bound to allosteric effectors.
AB  - The lac operon is a model system for understanding how effector molecules
      regulate transcription and are necessary for allosteric transitions. The crystal
      structures of the lac repressor bound to inducer and anti-inducer molecules
      provide a model for how these small molecules can modulate repressor function.
      The structures of the apo repressor and the repressor bound to effector molecules
      are compared in atomic detail. All effectors examined here bind to the repressor
      in the same location and are anchored to the repressor through hydrogen bonds to
      several hydroxyl groups of the sugar ring. Inducer molecules form a more
      extensive hydrogen-bonding network compared to anti-inducers and neutral effector
      molecules. The structures of these effector molecules suggest that the O6
      hydroxyl on the galactoside is essential for establishing a water-mediated
      hydrogen bonding network that bridges the N-terminal and C-terminal sub-domains.
      The altered hydrogen bonding can account in part for the different structural
      conformations of the repressor, and is vital for the allosteric transition.

PMID- 17543987
TI  - Mesophile versus thermophile: insights into the structural mechanisms of kinetic
      stability.
AB  - Obtaining detailed knowledge of folding intermediate and transition state (TS)
      structures is critical for understanding protein folding mechanisms. Comparisons
      between proteins adapted to survive extreme temperatures with their mesophilic
      homologs are likely to provide valuable information on the interactions relevant
      to the unfolding transition. For kinetically stable proteins such as alpha-lytic
      protease (alphaLP) and its family members, their large free energy barrier to
      unfolding is central to their biological function. To gain new insights into the
      mechanisms that underlie kinetic stability, we have determined the structure and
      high temperature unfolding kinetics of a thermophilic homolog, Thermobifida fusca
      protease A (TFPA). These studies led to the identification of a specific
      structural element bridging the N and C-terminal domains of the protease (the
      "domain bridge") proposed to be associated with the enhanced high temperature
      kinetic stability in TFPA. Mutagenesis experiments exchanging the TFPA domain
      bridge into alphaLP validate this hypothesis and illustrate key structural
      details that contribute to TFPA's increased kinetic thermostability. These
      results lead to an updated model for the unfolding transition state structure for
      this important class of proteases in which domain bridge undocking and unfolding
      occurs at or before the TS. The domain bridge appears to be a structural element
      that can modulate the degree of kinetic stability of the different members of
      this class of proteases.

PMID- 17543988
TI  - Photochemical tissue bonding: a promising technique for peripheral nerve repair.
AB  - BACKGROUND: Photochemical tissue bonding (PTB) is a novel tissue repair technique
      that uses visible light and a photosensitizing dye to crosslink proteins on
      tissue surfaces. This technique has been successfully demonstrated in a number of
      tissue repair models. An ideal nerve repair technique would be atraumatic and
      avoid placement of foreign bodies at the repair site. The epineurium is suited to
      photochemical repair as it is thin, translucent and has a relatively high
      collagen content. This study was designed to determine if PTB could be
      successfully applied in a peripheral nerve repair model. MATERIAL AND METHODS:
      Forty Sprague Dawley rats underwent transection of the sciatic nerve. Animals
      were then randomized to four treatment groups; epineurial suture repair,
      epineurial cuff with PTB, epineurial cuff alone, and no repair. Functional
      recovery was assessed at 10 day intervals using walking track analysis and
      sciatic function index calculations. At 90 days postoperatively animals were
      sacrificed and sciatic nerves harvested for histology and histomorphometry.
      RESULTS: Functional recovery in the suture repair and epineural cuff with PTB
      groups were not significantly different (-70.6 +/- 17.8 versus -76.9 +/- 10.3, P
      = 0.64) at 90 days postrepair. Histology showed good axonal regeneration with all
      repair techniques. Histomorphometric analysis found no significant difference
      between the repair groups. CONCLUSIONS: This study illustrates that peripheral
      nerves can be successfully repaired using a photochemical tissue bonding
      technique with results similar to those achieved with the current gold standard.
      With further development and refinement PTB may prove a useful tool in peripheral
      nerve repair.

PMID- 17543989
TI  - IL-10 attenuates hepatic I/R injury and promotes hepatocyte proliferation.
AB  - BACKGROUND: One of the most important determinants of the outcome of hepatic
      ischemia and reperfusion (I/R) injury is the onset of the inflammatory response.
      Interleukin-10 (IL-10) is a potent anti-inflammatory cytokine. It inhibits the
      production of interleukin-6 (IL-6), which however, also is involved in priming
      hepatocyte proliferation. The aim of this study was to examine the protective
      effects and the influence on the regenerative response of exogenous as well as
      endogenous IL-10 in a rat model of hepatic I/R injury. MATERIALS AND METHODS:
      Seventy percent Liver I/R was induced in male Wistar rats for 60 min followed by
      24 h reperfusion. One group underwent a midline laparotomy with recombinant rat
      (rr)IL-10 administration (SHAM + IL-10). The other groups underwent 60 min
      ischemia with administration of saline (I/R + saline), rrIL-10 [at two different
      time-points, i.e., I/R + IL-10pre(ischemia) and I/R + IL-10end(ischemia)] or anti
      rat IL-10 antibody (I/R + antiIL-10). RESULTS: Parenchymal damage, as assessed by
      plasma alanine aminotransferase and aspartate aminotransferase, was significantly
      reduced by rrIL-10 and by endogenous IL-10 (P < 0.05). Also, rrIL-10
      significantly reduced IL-6 production and the accumulation of neutrophils in
      liver and lung tissue, as measured by myeloperoxidase activity. Necrosis and
      apoptosis were significantly reduced and hepatocyte proliferation was stimulated
      by rrIL-10. CONCLUSIONS: RrIL-10 and, to a lesser extent, endogenous IL-10,
      attenuate damage and inflammation, while rrIL-10 also promotes proliferation
      after hepatic I/R injury in rats. Therefore, rrIL-10 has potential use to prevent
      I/R injury and to promote liver regeneration after partial liver resection with
      temporary inflow occlusion.

PMID- 17543990
TI  - Neither antioxidants nor COX-2 inhibition protect against esophageal inflammation
      in an experimental model of severe reflux.
AB  - BACKGROUND: Reflux-induced injury and oxidative stress result in esophageal
      inflammation and the potential for progression to intestinal metaplasia and
      adenocarcinoma. Proton-pump inhibitors represent the standard medical approach,
      but anti-inflammatories and antioxidants offer novel therapeutic possibilities.
      MATERIALS AND METHODS: Six weeks after an esophagojejunostomy reflux procedure,
      female Wistar rats (n = 100) were randomized to receive either an antioxidant
      (vitamin C, 8 mg or 28 mg/day), a cyclooxygenase-2 (COX-2) inhibitor (rofecoxib,
      1 mg/day), or no therapy. After sacrifice 16 weeks later, esophageal injury was
      scored using pathologic and image analysis scoring. RESULTS: Esophagitis was
      present in all 63 animals completing the study and severe in 27 (43%). No animal
      developed metaplasia or tumor. The extent of inflammation and esophageal
      ulceration were not significantly different between experimental groups.
      CONCLUSIONS: In this model of reflux injury, antioxidants and COX-2 inhibitors
      failed to ameliorate the severe inflammation induced. Further experimental
      designs should evaluate these novel approaches in less severe experimental
      models.

PMID- 17543991
TI  - Abnormal retinal thickness in patients with mild cognitive impairment and
      Alzheimer's disease.
AB  - In Alzheimer's disease (AD), brain lesions are marked by severe neuronal loss and
      retinal degeneration was previously mentioned in affected patients. Mild
      cognitive impairment (MCI) is a clinical syndrome that could be an early phase of
      AD. In this study, using optical coherence tomography (OCT), the retinal nerve
      fiber layer (RNFL) thickness was assessed in patients with mild AD, moderate to
      severe AD, amnestic MCI and control subjects. The results show that RNFL
      thickness is statistically reduced in patients with MCI, mild AD or moderate to
      severe AD compared to controls. In addition, no statistical difference was found
      between the results in MCI patients and mild AD patients. The RNFL seems to be
      involved early during the course of amnestic MCI and OCT tests could be carried
      out in patients with cognitive troubles.

PMID- 17543992
TI  - Lack of TDP-43 abnormalities in mutant SOD1 transgenic mice shows disparity with
      ALS.
AB  - Mislocalization of the TAR-DNA binding protein (TDP-43) from the nucleus to the
      cytoplasm of diseased motor neurons and association with intraneuronal
      ubiquitinated inclusions has recently been reported in amyotrophic lateral
      sclerosis (ALS). Here, we have investigated TDP-43 immunoreactivity in three
      lines of mutant SOD1 transgenic mice, G93A, G37R and G85R and compared with
      labeling in one sporadic ALS case and two familial ALS cases carrying mutations
      in SOD1, A4T and I113T. Our findings show that there is no mislocalization of TDP
      43 to the cytoplasm in motor neurons of mutant SOD1 transgenic mice, nor
      association of TDP-43 with ubiquitinated inclusions. In contrast, mislocalization
      of TDP-43 to the cytoplasm and association with ubiquitinated inclusions was
      found in the ALS cases, including those carrying mutations in SOD1.
      Interestingly, there was no association of TDP-43 with ubiquitinated hyaline
      conglomerate inclusions, pathology closely associated with ALS cases carrying
      mutations in SOD1. Our findings indicate that the process of motor neuron
      degeneration in mutant SOD1 transgenic mice is unlikely to involve the
      abnormalities of TDP-43 described in the human disease.

PMID- 17543993
TI  - Early music exposure modifies GluR2 protein expression in rat auditory cortex and
      anterior cingulate cortex.
AB  - GluR2, a major subunit in AMPA receptor, plays an important role in brain
      functional activity. We studied the effect of music exposure during development
      on the expression level of GluR2 proteins in the auditory cortex (AC) and
      anterior cingulate cortex (ACC) of SD rats. Rats were divided into three groups,
      Music1 (exposed to Nostalgy) group, Music2 (exposed to Wishmaster) group, and
      control (no music exposure) group. For music exposure groups, rats were exposed
      to music from postnatal day (PND) 14, and the expression levels of GluR2 proteins
      were determined at PND 28, 42 and 56. For the control group, the expression
      levels of GluR2 proteins were determined at PND1, 3, 5, 7, 9, 11, 14, 21, 28, 42,
      and 56. Results showed an age-dependent expression of GluR2 proteins in control
      rats. In AC, exposure to Music2 dramatically increased the expression of GluR2,
      while exposure to Music1 had no effect. In ACC, we found remarkable discrepancies
      in time-dependent expression of GluR2 between music exposed rats and control
      rats. These results indicate that exposure to music can modify the expression
      level of GluR2 protein in AC and ACC.

PMID- 17543994
TI  - Cytogenetic aberrations in neuropathy associated with IgM monoclonal gammopathy.
AB  - The occurrence and nature of cytogenetic aberrations in polyneuropathy associated
      with IgM monoclonal gammopathy was determined. Therefore, interphase fluorescence
      in situ hybridization (FISH) was applied in 22 patients with polyneuropathy
      associated with IgM monoclonal gammopathy, multiplex ligation-dependent probe
      amplification (MLPA) assay in 18 of these patients and genome-wide-array-based
      comparative genomic hybridization (CGH) in eight of these 18 patients. Four
      patients had 10-20% and one patient had 30% B cells with IgH rearrangements; one
      patient had additional loss of 14qter; one patient had amplification of 6p and
      loss of 6q. Cytogenetic aberrations may be found in one third of the patients
      with neuropathy associated with IgM monoclonal gammopathy and are mainly
      associated with indolent Waldenstrom's Macroglobulinemia.

PMID- 17543995
TI  - Surgical options in ICH including decompressive craniectomy.
AB  - Intracerebral haemorrhage (ICH) accounts for 15 to 20% of strokes. The condition
      carries a higher morbidity and mortality than occlusive stroke. Despite
      considerable research effort, no therapeutic modality either medical or surgical
      has emerged with clear evidence of benefit other than in rare aneurysmal cases.
      Intracerebral haemorrhages can be divided into those that arise from pre-existing
      macroscopic vascular lesions - so called "ictohaemorrhagic lesions", and those
      that do not; the latter being the commoner. Most of the research that has been
      done on the benefits of surgery has been in this latter group. Trial data
      available to date precludes a major benefit from surgical evacuation in a large
      proportion of cases however there are hypotheses of benefit still under
      investigation, specifically superficial lobar ICH treated by open surgical
      evacuation, deeper ICH treated with minimally invasive surgical techniques, and
      decompressive craniectomy. When an ICH arises from an ictohaemorrhagic lesion,
      therapy has two goals: to treat the effects of the acute haemorrhage and to
      prevent a recurrence. Three modalities are available for treating lesions to
      prevent recurrence: stereotactic radiosurgery, endovascular embolisation, and
      open surgical resection. As with ICH without an underlying lesion there is no
      evidence to support surgical removal of the haemorrhage in most cases. An
      important exception is ICHs arising from intracranial aneurysms where there is
      good evidence to support evacuation of the haematoma as well as repair of the
      aneurysm.

PMID- 17543996
TI  - Protein sequence design based on the topology of the native state structure.
AB  - Computational design of sequences for a given structure is generally studied by
      exhaustively enumerating the sequence space or by searching in such a large
      space, which is prohibitively expensive. However, we point out that the protein
      topology has a wealth of information, which can be exploited to design sequences
      for a chosen structure. In this paper, we present a computationally efficient
      method for ranking the residue sites in a given native-state structure, which
      enables us to design sequences for a chosen structure. The premise for the method
      is that the topology of the graph representing the energetically interacting
      neighbours in a protein plays an important role in the inverse-folding problem.
      While our previous work (which was also based on topology) used eigenspectral
      analysis of the adjacency matrix of interactions for ranking the residue sites in
      a given chain, here we use a simple but effective way of assigning weights to the
      nodes on the basis of secondary connections, along with primary connections. This
      indirectly accounts for the edge weight in the graph and removes degeneracy in
      the degree. The new scheme needs only a few multiplications and additions to
      compute the preferred ranking of the residue sites even for structures of real
      proteins of sizes of a few hundred amino acid residues. We use HP lattice model
      examples (for which exhaustive enumeration of sequences is practical) to validate
      our ranking approach in obtaining sequences of lowest energy for any H-P residue
      composition for a given native-state structure. Some examples of native
      structures of real proteins are also included. Quantitative comparison of the
      efficacy of the new scheme with the earlier schemes is made. The new scheme
      consistently performs better and with much lower computational cost. An
      optimization procedure is added to work with the new scheme in a few rare cases
      wherein the new scheme fails to provide the best sequence, an optimization
      procedure is added to work with the new scheme.

PMID- 17543997
TI  - A resolution of the paradox of enrichment.
AB  - Theoretical studies have shown a paradoxical destabilizing response of predator
      prey ecosystems to enrichment, but there is the gap between the intuitive view of
      nature and this theoretical prediction. We studied a minimal predator-prey system
      (a two predator-two prey system) in which the paradox of enrichment pattern can
      vanish; the destabilization with enrichment is reversed, leading to stabilization
      (a decrease in the amplitude of oscillation of population densities). For
      resolution of the paradox, two conditions must be met: (1) the same prey species
      must be preferred as a dietary item by both predator species, creating the
      potential for high exploitative competition between the predator species, and
      (2), while both predators are assumed to select their diet in accordance with
      optimal diet utilization theory, one predator must be a specialist and the other
      a generalist. In this system, the presence of a less profitable prey species can
      cause the increase in population oscillation amplitudes associated with
      increasing enrichment to be suppressed via the optimal diet utilization of the
      generalist predator. The resulting stabilization is explained by the mitigating
      effect of the less profitable prey showing better population growth with
      increasing enrichment on the destabilization underlying the specialist predator
      and prey relation, thus resolving the paradox of enrichment.

PMID- 17543998
TI  - Noisy attractors and ergodic sets in models of gene regulatory networks.
AB  - We investigate the hypothesis that cell types are attractors. This hypothesis was
      criticized with the fact that real gene networks are noisy systems and, thus, do
      not have attractors [Kadanoff, L., Coppersmith, S., Aldana, M., 2002. Boolean
      Dynamics with Random Couplings.
      http://www.citebase.org/abstract?id=oai:arXiv.org:nlin/0204062]. Given the
      concept of "ergodic set" as a set of states from which the system, once entering,
      does not leave when subject to internal noise, first, using the Boolean network
      model, we show that if all nodes of states on attractors are subject to internal
      state change with a probability p due to noise, multiple ergodic sets are very
      unlikely. Thereafter, we show that if a fraction of those nodes are "locked" (not
      subject to state fluctuations caused by internal noise), multiple ergodic sets
      emerge. Finally, we present an example of a gene network, modelled with a
      realistic model of transcription and translation and gene-gene interaction,
      driven by a stochastic simulation algorithm with multiple time-delayed reactions,
      which has internal noise and that we also subject to external perturbations. We
      show that, in this case, two distinct ergodic sets exist and are stable within a
      wide range of parameters variations and, to some extent, to external
      perturbations.

PMID- 17543999
TI  - Postoperative radiotherapy for maxillary sinus cancer: long-term outcomes and
      toxicities of treatment.
AB  - PURPOSE: To determine the effects of three changes in radiotherapy technique on
      the outcomes for patients irradiated postoperatively for maxillary sinus cancer.
      METHODS AND MATERIALS: The data of 146 patients treated between 1969 and 2002
      were reviewed. The patients were separated into two groups according to the date
      of treatment. Group 1 included 90 patients treated before 1991 and Group 2
      included 56 patients treated after 1991, when the three changes were implemented.
      The outcomes were compared between the two groups. RESULTS: No differences were
      found in the 5-year overall survival, recurrence-free survival, local control,
      nodal control, or distant metastasis rates between the two groups (51% vs. 62%,
      51% vs. 57%, 76% vs. 70%, 82% vs. 83%, and 28% vs. 17% for Groups 1 and 2,
      respectively). The three changes were to increase the portals to cover the base
      of the skull in patients with perineural invasion, reducing their risk of local
      recurrence; the addition of elective neck irradiation in patients with squamous
      or undifferentiated histologic features, improving the nodal control, distant
      metastasis, and recurrence-free survival rates (64% vs. 93%, 20% vs. 3%, and 45%
      vs. 67%, respectively; p < 0.05 for all comparisons); and improving the dose
      distributions within the target volume, reducing the late Grade 3-4 complication
      rates (34% in Group 1 vs. 8% in Group 2, p = 0.014). Multivariate analysis
      revealed advancing age, the need for enucleation, and positive margins as
      independent predictors of worse overall survival. The need for enucleation also
      predicted for worse local control. CONCLUSION: The three changes in radiotherapy
      technique improved the outcomes for select patients as predicted. Despite these
      changes, little demonstrable overall improvement occurred in local control or
      survival for these patients and additional work must be done.

PMID- 17544000
TI  - In vitro responsiveness of glioma cell lines to multimodality treatment with
      radiotherapy, temozolomide, and epidermal growth factor receptor inhibition with
      cetuximab.
AB  - BACKGROUND: The majority of glioblastoma multiforme (GBM) cells express the
      epidermal growth factor receptor (EGFR). The present study evaluates the
      combination of temozolomide (TMZ), EGFR inhibition, and radiotherapy (RT) in GBM
      cell lines. METHODS AND MATERIALS: Human GBM cell lines U87, LN229, LN18, NCH 82,
      and NCH 89 were treated with various combinations of TMZ, RT, and the monoclonal
      EGFR antibody cetuximab. Responsiveness of glioma cells to the combination
      treatment was measured by clonogenic survival. RESULTS: Overall, double and
      triple combinations of RT, TMZ, and cetuximab lead to additive cytotoxic effects
      (independent toxicity). A notable exception was observed for U87 and LN 18 cell
      lines, where the combination of TMZ and cetuximab showed substantial antagonism.
      Interestingly, in these two cell lines, the combination of RT with cetuximab
      resulted in a substantial increase in cell killing over that expected for
      independent toxicity. The triple combination with RT, cetuximab, and TMZ was
      nearly able to overcome the antagonism for the TMZ/cetuximab combination in U87,
      however only marginally in LN18, GBM cell lines. CONCLUSION: It appears that EGFR
      expression is not correlated with cytotoxic effects exerted by cetuximab.
      Combination treatment with TMZ, cetuximab and radiation resulted in independent
      toxicity in three out of five cell lines evaluated, the antagonistic effect of
      the TMZ/cetuximab combination in two cell lines could indicate that TMZ
      preferentially kills cetuximab-resistant cells, suggesting for some cross-talk
      between toxicity mechanisms. Expression of EGFR was no surrogate marker for
      responsiveness to cetuximab, alone or in combination with RT and TMZ.

PMID- 17544001
TI  - Threshold level of p53 required for the induction of apoptosis in X-irradiated
      MOLT-4 cells.
AB  - PURPOSE: To determine the threshold level for the initiation of apoptosis by
      studying the quantitative aspect of p53 response to DNA damage in individual
      cells, to better understand the process in X-ray-induced p53-dependent apoptosis.
      METHODS AND MATERIALS: Time-sequential changes in p53 protein level were obtained
      for X-irradiated MOLT-4 cells using flow cytometry and analyzed. RESULTS: The
      changes in the cellular frequency distribution pattern of p53 content could be
      divided into two parts at a certain p53 level. The p53 vs. side-scatter in flow
      cytometry showed the sequential changes of p53 increase followed by an increase
      in cell death. On the basis of these results we determined a threshold level of
      p53 for the initiation of apoptosis. The level was estimated to be (1.08 +/-
      0.05) x 10(5) molecules per cell, which was approximately threefold higher than
      the mean content of control cells. The minimum times for p53 level to reach this
      threshold level were independent of X-ray dose and 1.4-1.6 h. The times for the
      signal transduction from the p53 accumulation to disruption of the mitochondrial
      membrane potential, caspase-3 activation, and cell death were 1.6, 2.1, and 2.8
      h, respectively. CONCLUSIONS: The threshold level of p53 for the initiation of
      apoptosis and the time sequence in the course of apoptotic events were determined
      in X-irradiated MOLT-4 cells.

PMID- 17544002
TI  - Magnetic resonance-based treatment planning for prostate intensity-modulated
      radiotherapy: creation of digitally reconstructed radiographs.
AB  - PURPOSE: To develop a technique to create magnetic resonance (MR)-based digitally
      reconstructed radiographs (DRR) for initial patient setup for routine clinical
      applications of MR-based treatment planning for prostate intensity-modulated
      radiotherapy. METHODS AND MATERIALS: Twenty prostate cancer patients' computed
      tomography (CT) and MR images were used for the study. Computed tomography and MR
      images were fused. The pelvic bony structures, including femoral heads, pubic
      rami, ischium, and ischial tuberosity, that are relevant for routine clinical
      patient setup were manually contoured on axial MR images. The contoured bony
      structures were then assigned a bulk density of 2.0 g/cm(3). The MR-based DRRs
      were generated. The accuracy of the MR-based DDRs was quantitatively evaluated by
      comparing MR-based DRRs with CT-based DRRs for these patients. For each patient,
      eight measuring points on both coronal and sagittal DRRs were used for
      quantitative evaluation. RESULTS: The maximum difference in the mean values of
      these measurement points was 1.3 +/- 1.6 mm, and the maximum difference in
      absolute positions was within 3 mm for the 20 patients investigated. CONCLUSIONS:
      Magnetic resonance-based DRRs are comparable to CT-based DRRs for prostate
      intensity-modulated radiotherapy and can be used for patient treatment setup when
      MR-based treatment planning is applied clinically.

PMID- 17544003
TI  - Patient study of in vivo verification of beam delivery and range, using positron
      emission tomography and computed tomography imaging after proton therapy.
AB  - PURPOSE: To investigate the feasibility and value of positron emission tomography
      and computed tomography (PET/CT) for treatment verification after proton
      radiotherapy. METHODS AND MATERIALS: This study included 9 patients with tumors
      in the cranial base, spine, orbit, and eye. Total doses of 1.8-3 GyE and 10 GyE
      (for an ocular melanoma) per fraction were delivered in 1 or 2 fields. Imaging
      was performed with a commercial PET/CT scanner for 30 min, starting within 20 min
      after treatment. The same treatment immobilization device was used during imaging
      for all but 2 patients. Measured PET/CT images were coregistered to the planning
      CT and compared with the corresponding PET expectation, obtained from CT-based
      Monte Carlo calculations complemented by functional information. For the ocular
      case, treatment position was approximately replicated, and spatial correlation
      was deduced from reference clips visible in both the planning radiographs and
      imaging CT. Here, the expected PET image was obtained from an analytical model.
      RESULTS: Good spatial correlation and quantitative agreement within 30% were
      found between the measured and expected activity. For head-and-neck patients, the
      beam range could be verified with an accuracy of 1-2 mm in well-coregistered bony
      structures. Low spine and eye sites indicated the need for better fixation and
      coregistration methods. An analysis of activity decay revealed as tissue
      effective half-lives of 800-1,150 s. CONCLUSIONS: This study demonstrates the
      feasibility of postradiation PET/CT for in vivo treatment verification. It also
      indicates some technological and methodological improvements needed for optimal
      clinical application.

PMID- 17544004
TI  - Convection-enhanced delivery of an iodine tracer into rat brain for synchrotron
      stereotactic radiotherapy.
AB  - PURPOSE: To evaluate direct intracerebral and intratumoral iodine delivery as
      means to improve iodine distribution for synchrotron stereotactic radiotherapy
      (SSR) and to evaluate the corresponding X-ray dose distribution. METHODS AND
      MATERIALS: Healthy rats and F98 glioma-bearing rats received an iodinated
      contrast agent (iopamidol) intracerebrally either by bolus injection (5 microL
      over approximately 1 min) or by convection-enhanced delivery (infusion volumes of
      5, 10, and 20 microL at a rate of 0.5 microL/min). We used synchrotron computed
      tomography (CT) to determine the iodine distribution after completion of infusion
      and a Monte Carlo code to compute the resulting radiation dose in SSR. RESULTS:
      Post-infusion CT imaging revealed high iodine concentrations in the perfused area
      with both injection methods. The iodine concentration remained elevated, with an
      exponential decay time constant of approximately 50 min, well suited for SSR
      treatment. Convection-enhanced delivery was shown to provide more uniform and
      controlled volumes of distribution than bolus injection and was chosen to
      evaluate the corresponding X-ray dose distribution. Sharp dose gradients around
      the target and excellent sparing of the contralateral brain were achievable with
      low iodine concentrations in the surrounding healthy brain tissues and blood
      vessels. CONCLUSIONS: Convection-enhanced delivery is an effective method to
      deliver high iodine concentrations and could improve the outcome of iodine
      enhanced SSR.

PMID- 17544005
TI  - In regard to Ishikawa et al.: Cyclooxygenase-2 impairs treatment effect of
      radiotherapy for cervical cancer by inhibition of radiation-induced apoptosis
      (Int J Radiat Oncol Biol Phys 2006;66:1347-1355).

PMID- 17544006
TI  - In regard to Allen et al.: Fatal pneumonitis associated with intensity-modulated
      radiation therapy for mesothelioma (Int J Radiat Oncol Biol Phys 2006;65:640
      645).

PMID- 17544007
TI  - In regard to Miller et al.: Multiple sclerosis, brain radiotherapy and risk of
      neurotoxicity: the Mayo Clinic experience (Int J Radiat Oncol Biol Phys
      2006;66:1178-1186).

PMID- 17544010
TI  - Troglitazone acutely activates AMP-activated protein kinase and inhibits insulin
      secretion from beta cells.
AB  - Changes in AMP-activated protein kinase (AMPK) activity contribute to the
      regulation of insulin secretion. Troglitazone has been shown to lower serum
      insulin levels and protect beta cell function. The aim of the present study was
      to examine the effects of troglitazone on AMPK activity and insulin secretion in
      beta cells. Isolated rat islets and MIN6 cells were treated for a short (1 h) or
      a long time (20 h) with troglitazone. One-hour troglitazone treatment activated
      AMPK and inhibited both glucose-stimulated insulin secretion (GSIS) and the
      response of insulin secretion to combined stimuli of glucose and palmitate. Long
      (20 h) treatment with troglitazone caused a sustained phosphorylation of AMPK and
      acetyl-CoA carboxylase, and increased GSIS after withdrawal of the drug. This
      study provided evidence that troglitazone activated AMPK in beta cells. In
      addition to the insulin-sensitizing effects in peripheral tissues, troglitazone
      also directly inhibits insulin hypersecretion by the elevated glucose and fatty
      acids, and thus protects beta cells from glucolipotoxicity.

PMID- 17544011
TI  - Statistical properties of ion channel records. Part II: estimation from the
      macroscopic current.
AB  - Macroscopic ion channel current is the summation of the stochastic records of
      individual channel currents and therefore relates to their statistical
      properties. As a consequence of this relationship, it may be possible to derive
      certain statistical properties of single channel records or even generate some
      estimates of the records themselves from the macroscopic current when the direct
      measurement of single channel currents is not applicable. We present a procedure
      for generating the single channel records of an ion channel from its macroscopic
      current when the stochastic process of channel gating has the following two
      properties: (I) the open duration is independent of the time of opening event and
      has a single exponential probability density function (pdf), (II) all the
      channels have the same probability to open at time t. The application of this
      procedure is considered for cases where direct measurement of single channel
      records is difficult or impossible. First, the probability density function (pdf)
      of opening events, a statistical property of single channel records, is derived
      from the normalized macroscopic current and mean channel open duration. Second,
      it is shown that under the conditions (I) and (II), a non-stationary Markov model
      can represent the stochastic process of channel gating. Third, the non-stationary
      Markov model is calibrated using the results of the first step. The non
      stationary formulation increases the model ability to generate a variety of
      different single channel records compared to common stationary Markov models. The
      model is then used to generate single channel records and to obtain other
      statistical properties of the records. Experimental single channel records of
      inactivating BK potassium channels are used to evaluate how accurately this
      procedure reconstructs measured single channel sweeps.

PMID- 17544012
TI  - [Postpartum contraception: medical guidelines, women's point of view].
AB  - PURPOSE: Postpartum contraception is subjected to specific medical guidelines
      related to the suckling mode. The practitioner must conciliate prescription rules
      with women's expectations. The purpose of this work was to estimate the medical
      practice in the maternity centre at a local hospital and the actual practice of
      women at home, in immediate postpartum and during the year that followed the
      childbirth. METHOD: One hundred and four new mothers from the maternity centre,
      in September 2004, took the survey. During their stay after birth, they filled a
      questionnaire on contraception. Various data have been collected from their
      obstetrical file. The analysis allowed the synthesis of medical guidelines on
      postpartum contraception. One year later, patients answered a telephone survey
      about their contraceptive practice. RESULTS: In our survey, two-third of the new
      mothers (61.5%) chose breast-feeding. Seventy percent of them received progestins
      as contraceptives. Three out of four women (78%) followed this prescription after
      they left the hospital. Two-third (62.5%) of the women who had chosen artificial
      suckling received a prescription of estroprogestin. The majority of them (96%)
      used it after their return home. A high number of women (87.5%) estimated that
      these contraceptions were efficient, but more than a third of them thought they
      were uneasy to use (38.9%). Half of the women (52.8%) forgot their contraception
      during postpartum and the majority of them (86%) changed it within a year. A
      quarter (23.1%) of the contraception follow-up during this time was made by a
      general practitioner. CONCLUSION: The practice in the maternity centre generally
      follows medical guidelines. However, it seems important to adapt postpartum
      contraception to the real practice of women. The general practitioner plays a
      major role in this management, especially during well-baby visits.

PMID- 17544013
TI  - Prospective study of interaction between alcohol, NSAID use and polymorphisms in
      genes involved in the inflammatory response in relation to risk of colorectal
      cancer.
AB  - Inflammatory bowl disease predisposes to cancer of the colorectum, and the use of
      non-steroidal anti-inflammatory drugs (NSAIDs) decreases the risk; hence genetic
      variations that modify the inflammatory response may alter the risk of colorectal
      cancer (CRC). The purpose of this study was to determine if polymorphisms
      associated with an altered inflammatory response are associated with colorectal
      cancer risk, and to investigate the possible interaction with lifestyle factors
      such as alcohol use, smoking and NSAID use. We studied 355 adenocarcinoma cases
      and 753 control persons, nested within the prospective "Diet, Cancer and Health"
      study. None of the polymorphisms were associated with risk of colorectal cancer.
      A statistically significant interaction between PPARgamma2 Pro(12)Ala and alcohol
      was found, where alcohol use was associated with a 22% increased risk of CRC per
      10g alcohol/day among carriers of the variant allele but not among homozygous
      wild type allele carriers (P for interaction=0.02). Moreover, an interaction
      between DLG5 R30Q and NSAID use was found (P for interaction=0.02). Our results
      do not suggest that inborn variations in the inflammatory response play any major
      role in risk of colorectal cancer.

PMID- 17544014
TI  - The neural basis of temporal preparation: Insights from brain tumor patients.
AB  - When foreperiods (FPs) of different duration vary on a trial-by-trial basis
      equiprobably but randomly, the RT is faster as the FP increases (variable FP
      effect), and becomes slower as the FP on the preceding trial gets longer
      (sequential effects). It is unclear whether the two effects are due to a common
      mechanism or to two different ones. Patients with lesions on the right lateral
      prefrontal cortex do not show the typical FP effect, suggesting a deficit in
      monitoring the FP adequately [Stuss, D. T., Alexander, M. P., Shallice, T.,
      Picton, T. W., Binns, M. A., Macdonald, R., et al. (2005). Multiple frontal
      systems controlling response speed. Neuropsychologia, 43, 396-417]. The aim of
      this study was two-fold: (1) to replicate this neuropsychological result testing
      cerebral tumor patients before and after surgical removal of the tumor located
      unilaterally in the prefrontal, premotor or parietal cortex, respectively and (2)
      to investigate whether the sequential effects would change together with the FP
      effect (supporting single-process accounts) or the two effects can be dissociated
      across tumor locations (suggesting dual-process views). The results of an
      experiment with a variable FP paradigm show a significant reduction of the FP
      effect selectively after excision of tumors on right prefrontal cortex. On the
      other hand, the sequential effects were reliably reduced especially after
      surgical removal of tumors located in the left premotor region, despite a normal
      FP effect. The latter dissociation between the two effects supports a dual
      process account of the variable FP phenomena. This study demonstrates that
      testing acute cerebral tumor patients represents a viable neuropsychological
      approach for the fractionation and localisation of cognitive processes.

PMID- 17544015
TI  - Gender differences in the cognitive control of emotion: An fMRI study.
AB  - The interaction of emotion and cognition has become a topic of major interest.
      However, the influence of gender on the interplay between the two processes,
      along with its neural correlates have not been fully analysed so far. In this
      functional magnetic resonance imaging (fMRI) study we induced negative emotion
      using negative olfactory stimulation while male (n=21) and female (n=19)
      participants performed an n-back verbal working memory task. Based on findings
      indicating increased emotional reactivity in women, we expected the female
      participants to exhibit stronger activation in characteristically emotion
      associated areas during the interaction of emotional and cognitive processing in
      comparison to the male participants. Both groups were found to be significantly
      impaired in their working memory performance by negative emotion induction.
      However, fMRI analysis revealed distinct differences in neuronal activation
      between groups. In men, cognitive performance under negative emotion induction
      was associated with extended activation patterns in mainly prefrontal and
      superior parietal regions. In women, the interaction between emotion and working
      memory yielded a significantly stronger response in the amygdala and the
      orbitofrontal cortex (OFC) compared to their male counterparts. Our data suggest
      that in women the interaction of verbal working memory and negative emotion is
      associated with relative hyperactivation in more emotion-associated areas whereas
      in men regions commonly regarded as important for cognition and cognitive control
      are activated. These results provide new insights in gender-specific cerebral
      mechanisms.

PMID- 17544016
TI  - Patterns of surface temperatures in two mole-rats (Bathyergidae) with different
      social systems as revealed by IR-thermography.
AB  - Furred subterranean mammals face the problem of dissipating heat to the
      environment because high humidity and absence of air flow in sealed belowground
      tunnels constrain heat loss from body by convection and evaporation. In order to
      detect body areas responsible for heat loss, surface temperatures in two species
      of African mole-rats were measured at different ambient air temperatures by
      infrared thermography. Fur characteristics were also evaluated. Thinner pelage of
      the ventrum, its moderate temperature and large size suggest that ventral side of
      the body is the main thermal avenue for heat loss in both species. Interspecific
      differences could be explained by different fur characteristics connected with
      social thermoregulation. Compared to the social Fukomys mechowii, the solitary
      Heliophobius argenteocinereus has denser and longer fur on most of its body; its
      surface temperature was thus lower than in F. mechowii at lowered ambient
      temperatures. On the other hand, the denser and longer hair cover in H.
      argenteocinereus impedes heat dissipation at highest ambient temperatures (and
      probably also during digging activity) resulting in increase of core body
      temperature. H. argenteocinereus seems to be more sensitive to overheating than
      F. mechowii. At lower air temperatures, the social species may uses huddling to
      combat hypothermia.

PMID- 17544018
TI  - Reviving the vascular surgeon-scientist: an interim assessment of the jointly
      sponsored Lifeline Foundation/National Heart, Lung, and Blood Institute William
      J. von Liebig Mentored Clinical Scientist Development (K08) Program.
AB  - The Lifeline Foundation/National Heart, Lung, and Blood Institute William J. von
      Liebig Mentored Clinical Scientist Development (K08) Award program was
      established as a unique partnership to support vascular surgeon-scientists.
      Between 1999 and 2005, 39 applications were submitted, and the overall funding
      rate was 49% (14 von Liebig K08s and 5 additional NHLBI K08s). Vascular surgeon
      K08 recipients (median age, 38 years) had held faculty appointments for 2.5 +/-
      0.4 years, with 2.6 +/- 0.2 years of previous research experience and 28.4 +/-
      6.2 publications. These individuals subsequently authored 5.1 +/- 0.8 peer
      reviewed publications per recipient per year, of which 35% were research and 65%
      were clinical. Six of seven holding the K08 over 3 years had received academic
      promotion, and all five completing the 5-year award had achieved independent
      investigator status with National Institutes of Health support. The von Liebig
      K08 program has therefore been an effective vehicle to stimulate research career
      development in the field of vascular surgery.

PMID- 17544019
TI  - Translational control in endothelial cells.
AB  - Cellular phenotype and function is ultimately determined by the synthesis of
      proteins derived from a genetic blueprint. Control of gene expression occurs at
      multiple checkpoints, including the transcription of DNA into RNA and the
      translation of RNA into protein. Translational control mechanisms are important
      regulators of cellular phenotype, controlling up to 10% of overall cellular gene
      expression, yet they remain relatively understudied when compared with
      transcriptional control mechanisms. Specific regulation of protein synthesis from
      messenger RNA transcripts allows cells to temporally unlink translation from
      transcription and provides a mechanism for a more rapid response to environmental
      signals than if transcription were required. We discuss some of the fundamental
      concepts of translational control, tools for studying it and its relevance to
      vascular cells, in particular the endothelium.

PMID- 17544020
TI  - Smooth muscle cell signal transduction: implications of vascular biology for
      vascular surgeons.
AB  - Vascular smooth muscle cells exhibit varied responses after vessel injury and
      surgical interventions, including phenotypic switching, migration, proliferation,
      protein synthesis, and apoptosis. Although the source of the smooth muscle cells
      that accumulate in the vascular wall is controversial, possibly reflecting
      migration from the adventitia, from the circulating blood, or in situ
      differentiation, the intracellular signal transduction pathways that control
      these processes are being defined. Some of these pathways include the Ras-mitogen
      activated protein kinase, phosphatidylinositol 3-kinase-Akt, Rho, death receptor
      caspase, and nitric oxide pathways. Signal transduction pathways provide
      amplification, redundancy, and control points within the cell and culminate in
      biologic responses. We review some of the signaling pathways activated within
      smooth muscle cells that contribute to smooth muscle cell heterogeneity and
      development of pathology such as restenosis and neointimal hyperplasia.

PMID- 17544021
TI  - Regulation of vascular smooth muscle cell differentiation.
AB  - Vascular smooth muscle cell (VSMC) differentiation is an essential component of
      vascular development. These cells perform biosynthetic, proliferative, and
      contractile roles in the vessel wall. VSMCs are not terminally differentiated and
      are able to modulate their phenotype in response to changing local environmental
      cues. There is clear evidence that alterations in the differentiated state of the
      VSMC play a critical role in the pathogenesis of atherosclerosis and intimal
      hyperplasia, as well as in a variety of other major human diseases, including
      hypertension, asthma, and vascular aneurysms. The focus of this review is to
      provide an overview of the current state of knowledge of molecular mechanisms
      involved in controlling phenotypic switching of SMCs, with particular focus on
      examination of signaling pathway that regulate this process.

PMID- 17544022
TI  - Integrin alpha(v)beta(3) as a target in the prevention of neointimal hyperplasia.
AB  - Although major advances have been made in the prevention and treatment of
      restenosis following coronary and peripheral interventions, the persistent
      complications of thrombosis and reintervention remain a mainstay for repeat
      hospitalizations in this patient population. For many years, a ubiquitous cell
      surface receptor called alpha(v)beta(3) integrin was the target of investigators
      in the prevention of restenosis because its interaction with the extracellular
      matrix was believed to coordinate the migration of smooth muscle cells (SMCs)
      from the media to the intima, the seminal event in the formation of intimal
      occlusive lesion. After the publication of uniformly positive animal studies
      demonstrating that alpha(v)beta(3) integrin blockade led to a significant
      reduction in new intimal (neointimal) lesion formation, early clinical trials
      supported the association of avoidance of target lesion revascularization and the
      use of antagonists to the SMC integrin alpha(v)beta(3) and its related platelet
      integrin alpha(IIb)beta(3). However, a series of clinical trials subsequently
      demonstrated that these antagonists did not necessarily prevent
      revascularizations by inhibiting intimal hyperplasia per se. Additional animal
      studies subsequently showed that, indeed, in the setting of pre-existing SMCs in
      the intimal lesion (ie, atherosclerotic plaque, fatty streaks), inhibiting SMC
      migration by way of beta(3) integrin blockade was an ineffective approach in the
      prevention of intimal hyperplasia and restenosis. However, given the wealth of
      basic and clinical information on the alpha(v)beta(3) integrin and its
      antagonists, we discuss in this article our new approach to this old solution by
      targeting a new clinical problem of early failure arteriovenous access for
      hemodialysis. Given the uniqueness of arteriovenous access in that there are
      essentially no significant atherosclerotic lesions in the artery and vein prior
      to the anastomosis, the seminal event of the migration of SMCs from the media to
      the neointima could by targeted once again with beta(3) integrin antagonists.

PMID- 17544023
TI  - Angiogenesis and vasculogenesis: inducing the growth of new blood vessels and
      wound healing by stimulation of bone marrow-derived progenitor cell mobilization
      and homing.
AB  - During embryonic development, the vasculature is among the first organs to form
      and is in charge of maintaining metabolic homeostasis by supplying oxygen and
      nutrients and removing waste products. As one would expect, blood vessels are
      critical not only for organ growth in the embryo but also for repair of wounded
      tissue in the adult. An imbalance in angiogenesis (a time-honored term that
      globally refers to the growth of new blood vessels) contributes to the
      pathogenesis of numerous malignant, inflammatory, ischemic, infectious, immune,
      and wound-healing disorders. This review focuses on the central role of the
      growth of new blood vessels in ischemic and diabetic wound healing and defines
      the most current nomenclature that describes the neovascularization process in
      wounds. There are now two well-defined, distinct, yet interrelated processes for
      the formation of postnatal new blood vessels, angiogenesis, and vasculogenesis.
      Reviewed are recent new data on vasculogenesis that promise to advance the field
      of wound healing.

PMID- 17544024
TI  - The chemokine system in arteriogenesis and hind limb ischemia.
AB  - Chemokines (chemotactic cytokines) are important in the recruitment of leukocytes
      to injured tissues and, as such, play a pivotal role in arteriogenesis and the
      tissue response to ischemia. Hind limb ischemia represents a complex model with
      arteriogenesis (collateral artery formation) occurring in tissues with normal
      perfusion while areas exhibiting ischemic necrosis undergo angiogenesis and
      skeletal muscle regeneration; monocytes and macrophages play an important role in
      all three of these processes. In addition to leukocyte trafficking, chemokines
      are produced by and chemokine receptors are present on diverse cell types,
      including myoblasts, endothelial, and smooth muscle cells. Thus, the chemokine
      system may have direct effects as well as inflammatory-mediated effects on
      arteriogenesis, angiogenesis, and skeletal muscle regeneration. This article
      reviews the complexity of the hind limb ischemia model and the role of the
      chemokine system in arteriogenesis and the tissue response to ischemia. Special
      emphasis will be placed on the roles of monocytes/macrophages and CCL2/monocyte
      chemotactic protein-1 (MCP-1) in these processes.

PMID- 17544026
TI  - The role of nitric oxide in the pathophysiology of intimal hyperplasia.
AB  - Since its discovery, nitric oxide (NO) has emerged as a biologically important
      molecule and was even named Molecule of the Year by Science magazine in 1992.
      Specific to our interests, NO has been implicated in the regulation of vascular
      pathology. This review begins with a summary of the molecular biology of NO, from
      its discovery to the mechanisms of endogenous production. Next, we turn our
      attention to describing the arterial injury response of neointimal hyperplasia,
      and we review the role of NO in the pathophysiology of neointimal hyperplasia.
      Finally, we review the literature regarding NO-based therapies. This includes the
      development of inhalational-based NO therapies, systemically administered L
      arginine and NO donors, NO synthase gene therapy, locally applied NO donors, and
      NO-releasing prosthetic materials. By reviewing the current literature, we
      emphasize the tremendous clinical potential that NO-based therapies can have on
      the development of neointimal hyperplasia.

PMID- 17544027
TI  - Molecular engineering of vein bypass grafts.
AB  - Surgical bypass of arterial occlusions using autogenous vein provides an
      effective treatment for many patients with advanced coronary or peripheral
      atherosclerosis. However, the long-term benefit of bypass surgery is limited by
      the development of de novo occlusive lesions within the vein graft, which occurs
      in a significant percentage of patients over time. The pathophysiology of vein
      graft failure involves a complex interplay between an acute vascular injury
      response and the hemodynamic adaptation of the vein to arterial forces. Cell
      proliferation, inflammation, and matrix metabolism are critical components of
      postimplantation remodeling. Conventional pharmacotherapy has had limited impact
      on graft failure. Vein grafts present a unique and attractive opportunity for
      molecular engineering, which is defined for purposes of this review as the local
      application of genomic (eg, gene transfer or gene inhibition) or proteomic
      interventions designed to alter the healing response. The critical enabling
      technologies for these strategies are described, with a perspective on
      preclinical and clinical development for this indication. The recently completed
      clinical trials of edifoligide (E2F decoy oligodeoxynucleotide) provide important
      lessons for future studies. A better understanding of the remodeling response of
      vein grafts in humans is required to design effective molecular therapies and to
      define the appropriate target populations and surrogate markers for future
      clinical trials.

PMID- 17544025
TI  - Clinical, cellular, and molecular aspects of arterial calcification.
AB  - Arterial calcification is a complex and independently regulated process with risk
      factors similar to those for atherosclerotic occlusive disease. It may develop
      either within the atherosclerotic intima or in the media. When calcification is
      found in coronary or lower extremity arteries, it is an independent predictor of
      cardiovascular events and lower extremity amputation. Recent evidence suggests a
      role for several endogenous stimulators and inhibitors in the pathogenesis of
      arterial calcification. Inflammatory mediators and matrix-degrading enzymes are
      also thought to control the progression of calcification in humans. Current
      research involves efforts to define the complex interactions between cellular and
      molecular mediators of arterial calcification.

PMID- 17544028
TI  - Genomic and proteomic determinants of lower extremity revascularization failure:
      rationale and study design.
AB  - This translational research program applies a working model of advanced
      functional genomics/proteomics and bioinformatics to human peripheral arterial
      occlusive disease (PAOD). It is a multidisciplinary collaborative effort of
      clinicians, scientists, and statisticians with an advisory panel consisting of
      experts in inflammation biology, vascular biology, molecular genetics,
      bioinformatics, clinical trial design, and epidemiology. The proposed human
      initiative is designed to study 300 symptomatic patients with PAOD undergoing
      medical management with or without vascular intervention by lower extremity
      angioplasty/stenting or vein graft bypass. The study aims to test the hypothesis
      that the systemic inflammatory response after vascular intervention influences
      the local milieu responsible for vascular repair and adaptation. The expectation
      is that this response is not uniform in all patients but, rather, is modulated by
      either preoperative genetic predisposition or postprocedure differential
      regulation of the innate immune response to injury that promotes a maladaptive
      phenotype leading to intervention failure. Therefore, some of these differences
      may be present and detectable before intervention and amenable to class
      prediction and prospective treatment strategies, whereas others may be detectable
      in the early postprocedural period, before the onset of clinical failure,
      permitting interventions to prevent an adverse outcome. The combination of
      genomic/proteomic data together with functional and quality-of-life outcome
      measures to define a critical model for class prediction and analysis should lead
      to new knowledge about failure mechanisms of vascular intervention and new
      strategies to improve existing approaches to lower extremity revascularization.

PMID- 17544029
TI  - Cytokines and the early vein graft: strategies to enhance durability.
AB  - This brief review focuses on experimental studies linking the proinflammatory
      cytokine tumor necrosis factor-alpha to accelerated vein graft failure in the
      broader historical context of vein graft research. From some perspectives, the
      field appears ripe for transfer of cytokine knowledge and therapeutic approaches
      that have evolved in other systems to vascular surgery problems. However, the
      complexity of vein graft disease suggests that more robust research approaches,
      such as broadening of the scope beyond focus on single mediators and neointimal
      hyperplasia, will be necessary to reach translatable strategies to prolong human
      vein graft durability.

PMID- 17544030
TI  - Tissue engineering applications to vascular bypass graft development: the use of
      adipose-derived stem cells.
AB  - The burgeoning field of vascular tissue engineering holds promise for the
      creation of a practical and successful small-diameter arterial bypass graft. Many
      creative combinations of autologous cells and scaffolds exist along with an
      equally long list of microenvironmental cues used to create a functional arterial
      conduit. This review outlines our work using abdominal wall fat as a source of
      autologous stem cells for vascular tissue engineering, focusing specifically on
      this stem cell's availability and potency to differentiate into endothelial-like
      cells. In a series of 49 patients undergoing elective peripheral vascular
      surgery, an abundant quantity of adult stem cells was harvested from fat obtained
      by liposuction. The efficacy of the isolation did not appear influenced by
      advanced age, obesity, renal failure, or vascular disease, although fat from
      diabetic patients yielded significantly less stem cells. In addition, these
      adipose-derived stem cells acquired several morphologic and molecular endothelial
      phenotypes when exposed to growth factors (endothelial cell growth supplement and
      vascular endothelial growth factor) and physiologic shear stress in vitro. Taken
      together, these studies suggest that fat appears to be a viable source of
      autologous stem cells for use in vascular tissue engineering.

PMID- 17544031
TI  - Novel thromboresistant materials.
AB  - The development of a clinically durable small-diameter vascular graft as well as
      permanently implantable biosensors and artificial organ systems that interface
      with blood, including the artificial heart, kidney, liver, and lung, remain
      limited by surface-induced thrombotic responses. Recent breakthroughs in
      materials science, along with a growing understanding of the molecular events
      that underlay thrombosis, has led to the design and clinical evaluation of a
      variety of biologically active coatings that inhibit components of the
      coagulation pathway and platelet responses by surface immobilization or
      controlled release of bioactive agents. This report reviews recent progress in
      generating synthetic thromboresistant surfaces that inhibit (1) protein and cell
      adsorption, (2) thrombin and fibrin formation, and (3) platelet activation and
      aggregation.

PMID- 17544032
TI  - Molecular characterization of post-thrombotic syndrome.
AB  - The post-thrombotic syndrome represents a poorly understood and significant
      vascular health problem. This review focuses on our current understanding of the
      pathogenesis of post-thrombotic syndrome. We emphasize the cellular and molecular
      mechanisms that are responsible for the critical components of post-thrombotic
      syndrome. These include the initiation of deep venous thrombosis, the
      pathogenesis of elevated venous pressure, and the factors responsible for
      nonhealing of venous stasis ulcers.

PMID- 17544033
TI  - Assessing the effectiveness of endografts: clinical and experimental
      perspectives.
AB  - The increasing use of endografts to treat abdominal aortic aneurysms has prompted
      the need for improved postoperative imaging and surveillance. Although patients
      benefit from decreased morbidity with endovascular repair compared with open
      abdominal aortic aneurysm repair, the long-term outcome of stent repair has yet
      to be fully determined. The persistence of endoleaks highlights the need for
      close follow-up, particularly because this may lead to aneurysm rupture, even
      after endograft repair. The current mainstay of assessing the healing of
      endografts is obtaining serial helical computed tomography angiography (CTA) to
      identify endoleaks, graft migration, thrombosis, and structural failure. CTA is
      not completely effective at identifying endoleaks and predicting aneurysm
      rupture, however. Other modalities have been studied to improve on current
      imaging methods, including three-dimensional CTA with volumetric analysis,
      contrast-enhanced duplex ultrasound imaging, cine magnetic resonance angiography,
      and explant analysis. In vitro and large-animal models of abdominal aortic
      aneurysm have also been developed to study the pathophysiology and treatment
      response of aneurysm exclusion. Thus, clinical and experimental models of
      endograft healing are attempting to define the optimal method of postoperative
      surveillance of endovascular repair.

PMID- 17544034
TI  - Impact of outcomes research on the management of vascular surgery patients.
AB  - Vascular surgery has traditionally relied on prospective, randomized clinical
      trials, case-control series from single institutions of excellence, and case
      studies to guide clinical decision-making. However, the use of a number of new
      clinical research tools has allowed the vascular surgeon to more critically
      assess the indications for particular operations, the costs of various procedures
      from both a monetary and quality-of-life standpoint, and the "real world"
      outcomes that can be expected from practitioners across the United States, not
      just from centers of excellence. Decision analysis with modeling of cohorts with
      desired characteristics and vascular disease has allowed for the objective
      determination of procedural cost-effectiveness and evaluation of patient quality
      of-life issues surrounding vascular procedures. The use of large national
      administrative databases has yielded important information concerning factors
      associated with improved outcomes after several vascular procedures across the
      entire United States, especially after relatively uncommon operations, such as
      thoracoabdominal aortic aneurysm repair. Administrative data have also enabled us
      to learn that access to various new endovascular procedures is somewhat limited,
      especially for the uninsured or poor. Hospital and surgeon volume, as a surrogate
      marker for quality, has been directly correlated with lower morbidity and
      mortality as well as differences in perioperative complications after multiple
      vascular procedures. A certificate of added qualification in General Vascular
      Surgery has also been shown to improve outcomes in patients undergoing vascular
      procedures. Finally, pioneered by the Veteran's Affairs administration and
      championed by the American College of Surgeons, prospectively collected data
      (National Surgery Quality Improvement Program) from the Veteran's Affairs and
      private sector hospitals is providing high-quality, risk-adjusted feedback about
      multiple vascular procedures to the hospital and the individual practitioner.
      Importantly, the body of literature generated using these new clinical research
      tools is being monitored by insurers and patients, as well as by the surgeons
      providing the care. This ultimately will have a direct impact on practice and
      referral patterns. It is therefore mandatory that vascular surgeons understand
      these new tools so that we can police our own practices before others, such as
      insurance companies and hospital administrators, do it for us.

PMID- 17544035
TI  - Functional outcome of critical limb ischemia.
AB  - Results of treatment for critical limb ischemia have traditionally focused on
      physician-oriented end points related to limb salvage surgery. Although numerous
      studies have demonstrated excellent patency and limb salvage after surgical
      revascularization procedures, survival in this patient population is poor,
      comorbidities reducing quality of life are rampant, and recovery from limb
      salvage surgery can be prolonged and complicated despite "success" as defined by
      traditional reporting methods. Patient-oriented outcome end points, such as
      health- related quality of life and functional status, are essential in defining
      optimal treatment options for the population of patients with critical limb
      ischemia. This area of research remains in its infancy, but will become
      increasingly important as the population of patients with critical limb ischemia
      and treatment options for these patients continue to expand. The current status
      and future outlook of functional and quality of life assessment of patients with
      critical limb ischemia is reviewed.

PMID- 17544037
TI  - Randomized clinical trials: how will results influence clinical practice in the
      management of symptomatic and asymptomatic extracranial carotid occlusive
      disease?
AB  - Evaluation of the efficacy of carotid endarterectomy and stenting requires
      careful consideration of clinical trial methodology as applied to the primary
      clinical end points of the specific trial. Although publication of observational
      data including registries is helpful in selecting options for further study,
      these reports are not considered replacements for the randomized clinical trial.
      This article reviews methodology and results of registries and randomized
      clinical trials. Pending publication of larger clinical trials on the management
      of symptomatic and asymptomatic carotid stenosis within the next 1 to 3 years,
      carotid endarterectomy remains the preferred technique for cerebral
      revascularization. The only exceptions to this recommendation come from higher
      risk categories of patients; however, their identification is frequently
      difficult and controversial.

PMID- 17544036
TI  - Percutaneous treatment of peripheral vascular disease: the role of diabetes and
      inflammation.
AB  - Peripheral arterial disease (PAD) is a growing health problem for many Americans
      and often occurs along with other cardiovascular risk factors, including diabetes
      mellitus (DM), low-grade inflammation, hypertension, and lipid disorders.
      Intermittent claudication (IC), an early manifestation of PAD, commonly leads to
      reduced quality of life for patients who are limited in their ambulation. While
      recent wide adoption of percutaneous peripheral interventional (PPI) techniques
      has increased the number patients being aggressively treated for IC, the overall
      effectiveness of PPI for the treatment of IC is not well known, especially for DM
      patients who have both hemodynamic and functional obstacles to treatment success.
      This review is designed to illustrate how treatment outcomes for IC can be
      measured by different modalities and how diabetes and inflammation can influence
      those outcomes. In the setting of greater concern for health care resources and
      clinical accountability, better understanding of treatment outcomes and efficacy
      will help us manage these complex challenges.

PMID- 17544038
TI  - An alkaloid, two conjugate sesquiterpenes and a phenylpropanoid from
      Pachypodanthium confine Engl. and Diels.
AB  - Two sesquiterpene-trimethoxystyrene conjugates (E)-1-[3'-(4'',8''-dimethylnona
      3'',7''-dienyl)cyclohex-3'-enyl]-2,4,5-trimethoxybenzene (1) and (Z)-1-[3'
      (4'',8''-dimethylnona-3'',7''-dienyl)cyclohex-3'-enyl]-2,4,5-trimethoxybenzene
      (2), a phenylpropanoid 1,2,4-trimethoxy-5-(1-methoxy-ethyl)-benzene (3), and an
      aporphine alkaloid N-acetylpachypodanthine (4), were isolated in addition to
      several known compounds from cyclohexane, dichloromethane and alkaloid extracts
      from bark of Pachypodanthium confine. The structures of these compounds were
      established based on the interpretation of their high resolution NMR (HSQC, HMBC,
      COSY and NOESY) spectral data.

PMID- 17544039
TI  - ["Top 15" medical journals downloaded in Paris public hospitals].

PMID- 17544040
TI  - [Hyperintense basal ganglia on T1-weighted images in Rendu-Osler-Weber disease].

PMID- 17544041
TI  - Recent results on the spatiotemporal modelling and comparative analysis of Black
      Death and bubonic plague epidemics.
AB  - BACKGROUND: This work demonstrates the importance of spatiotemporal stochastic
      modelling in constructing maps of major epidemics from fragmentary information,
      assessing population impacts, searching for possible etiologies, and performing
      comparative analysis of epidemics. METHODS: Based on the theory previously
      published by the authors and incorporating new knowledge bases, informative maps
      of the composite space-time distributions were generated for important
      characteristics of two major epidemics: Black Death (14th century Western Europe)
      and bubonic plague (19th-20th century Indian subcontinent). RESULTS: The
      comparative spatiotemporal analysis of the epidemics led to a number of
      interesting findings: (1) the two epidemics exhibited certain differences in
      their spatiotemporal characteristics (correlation structures, trends, occurrence
      patterns and propagation speeds) that need to be explained by means of an
      interdisciplinary effort; (2) geographical epidemic indicators confirmed in a
      rigorous quantitative manner the partial findings of isolated reports and time
      series that Black Death mortality was two orders of magnitude higher than that of
      bubonic plague; (3) modern bubonic plague is a rural disease hitting harder the
      small villages in the countryside whereas Black Death was a devastating epidemic
      that indiscriminately attacked large urban centres and the countryside, and while
      the epidemic in India lasted uninterruptedly for five decades, in Western Europe
      it lasted three and a half years; (4) the epidemics had reverse areal extension
      features in response to annual seasonal variations. Temperature increase at the
      end of winter led to an expansion of infected geographical area for Black Death
      and a reduction for bubonic plague, reaching a climax at the end of spring when
      the infected area in Western Europe was always larger than in India. Conversely,
      without exception, the infected area during winter was larger for the Indian
      bubonic plague; (5) during the Indian epidemic, the disease disappeared and
      reappeared several times at most locations; in Western Europe, once the disease
      entered a place, it lasted a time proportional to the population and then
      disappeared for several years (this on-and-off situation lasted more than three
      centuries); and (6) on average, Black Death moved much faster than bubonic plague
      to reach virgin territories, despite the fact that India is only slightly larger
      in area than Western Europe and had a railroad network almost instantly moving
      infected rats, fleas, and people from one end of the subcontinent to the other.
      CONCLUSIONS: These findings throw new light on the spatiotemporal characteristics
      of the epidemics and need to be taken into consideration in the scientific
      discussion concerning the two devastating diseases and the lessons learned from
      them.

PMID- 17544042
TI  - Effects of aerobic exercise on lipids and lipoproteins in adults with type 2
      diabetes: a meta-analysis of randomized-controlled trials.
AB  - OBJECTIVE: To conduct a meta-analysis of randomized-controlled trials in order to
      examine the effects of 8 weeks or more of aerobic exercise on lipids and
      lipoproteins in adults with Type 2 diabetes. METHODS: Studies were included if
      total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density
      lipoprotein cholesterol (LDL-C), ratio of TC to HDL-C (TC/HDL-C), triglycerides
      (TG), or all of the above, were assessed. A secondary outcome was glycosylated
      haemoglobin (HbA1). RESULTS: Seven studies representing 220 men and women (112
      exercise, 108 control) were available for pooling. Using a random-effects model,
      a statistically significant reduction of about 5% was found for LDL-C, whereas no
      statistically significant improvements were found for TC, HDL-C, TC/HDL-C or TG.
      A trend for a statistically significant reduction in HbA1 was also found.
      CONCLUSIONS: Although our overall results suggest that aerobic exercise lowers
      LDL-C in adults with Type 2 diabetes, additional randomized-controlled trials are
      needed on this topic.

PMID- 17544043
TI  - Implications of the International Health Regulations (2005) for communicable
      disease surveillance systems: Tunisia's experience.
AB  - BACKGROUND: In May 2005, the revised International Health Regulations, known as
      IHR (2005), were adopted in response to the evolving nature of communicable
      diseases (CD) and the rapid increase in global trade and travel. CD surveillance
      is an integral part of a country's core requirements under the regulations.
      METHODS: The implications of these requirements were assessed as part of a review
      of the national CD surveillance system of Tunisia using a qualitative methodology
      of strengths, weaknesses, opportunities and threats (SWOT). RESULTS: Tunisia is
      some way towards meeting the requirements of IHR (2005) while some specific areas
      that need to be addressed are highlighted for improvement: standardization of
      surveillance documents, strengthening the role of the laboratory in surveillance,
      increased human resources and training. CONCLUSIONS: Tunisia's experience can
      offer some lessons to other countries in this process. While meeting the capacity
      obligations of IHR (2005) requires investment and commitment, this investment
      will enable countries to better protect themselves against public health
      emergencies arising within their borders and threatening from elsewhere in the
      world.

PMID- 17544044
TI  - [Post-treatment surveillance for potentially curable malignancies].
AB  - Through an enormous research effort over the past five decades and especially due
      to early screening, an increasing number of cancers are potentially curable.
      Patients expand immeasurable energy in adhering to treatment plans and supportive
      care. Unfortunately, nothing prepares them for the anxiety that often comes with
      completion of therapy. More importantly, physicians are not properly equipped
      with data from controlled trials to define appropriate post-treatment
      surveillance, data with which they could educate patients and allay their fears.
      The goal of post-treatment surveillance is to enable the early detection of
      relapses and thus enhance the possibility of subsequent cure. Accordingly special
      follow-up is appropriate only for patients who can receive a second-line therapy.
      Clinical trials support conservative, rather than aggressive, surveillance to
      detect curable local relapse of breast tumors and potentially surgically curable
      metastases (mainly in the liver) of colon cancer. For germ-cell tumors, second
      line treatments are potentially curative in nearly all instances. Follow-up for
      other cancers depends on patients' anxiety levels and on the costs of
      surveillance.

PMID- 17544045
TI  - [Management of acute-stage myocardial infarction outside coronary care units.
      Recommendations--short text].

PMID- 17544046
TI  - Evaluation of indigenous milk ELISA with m-culture and m-PCR for the diagnosis of
      bovine Johne's disease (BJD) in lactating Indian dairy cattle.
AB  - Present study is the first attempt to evaluate an indigenous milk ELISA with milk
      culture, standardize milk PCR, estimate lacto-prevalence of Map and genotype Map
      DNA from milk samples in few Indian dairy herds. In all 115 cows were sampled
      from 669 lactating cows in six dairy herds from three districts of North India.
      Fifty milk samples (four herds) were screened by three tests (milk culture, m
      ELISA and m-PCR). Lacto-prevalence of Map in four dairy herds was 84.0% (50.0% in
      fat and 62.0% in sediment). Screening of both fat and sediment increased the
      sensitivity of culture. Colonies appeared between 45 and 120 DPI. In indigenous m
      ELISA, protoplasmic antigen derived from native Map 'Bison type' strain of goat
      origin was used. Screening of 115 lactating cows by m-ELISA ('herd screening
      test') detected 32.1% positive lactating cows (lacto-prevalence). Sensitivity of
      ELISA was 28.5% and 42.8% in single point cutoff and S/P ratio, respectively.
      Lacto-prevalence of JD was high in dairy herds (66.6-100.0% by culture and 20.0
      50.0% by m-ELISA). DDD farm, Mathura had very high (95.8%) and moderate
      prevalence of Map and lacto-antibodies, respectively. All cows were clinically
      suffering from JD. Specific IS 900 PCR was standardized in decontaminated fat and
      sediment of milk samples. DNA isolated from decontaminated pellets was amplified
      and characteristic 229 bp band was confirmatory for Map. Of the 50 milk samples,
      6.0% were positive in m-PCR. The test needs further standardization. Map DNA were
      genotyped as Map 'Bison type' by IS 1311 PCR-REA. Of the three tests, milk
      culture was most sensitive followed by m-ELISA and m-PCR. Map DNA isolated from
      milk samples of dairy cattle were first time genotyped as Map, 'Bison type' in
      India. High prevalence of Map in milk of dairy herds, posed major health hazard
      for calves and human beings.

PMID- 17544047
TI  - Diagnostic tests for infectious diseases in the developing world: two sides of
      the coin.
AB  - Effective and affordable diagnostics are crucial for health improvement in
      developing countries but are not accessible to those who need them most. Recent
      interest highlights innovative technological approaches for overcoming the
      problem, but these must be balanced by the efforts and research needed to ensure
      effective implementation in the context of often fragile health systems in low
      income countries in the developing world.

PMID- 17544048
TI  - Inhibitors of the sodium potassium ATPase that impair herpes simplex virus
      replication identified via a chemical screening approach.
AB  - Small molecules can provide valuable tools to investigate virus biology. We
      developed a chemical screening approach to identify small molecule inhibitors of
      poorly understood, pre-early gene expression steps in herpes simplex virus
      infection, using green fluorescent protein fused to an early protein. Our assay
      identified ouabain, a cardiac glycoside. Ouabain reversibly decreased viral yield
      by 100-fold without affecting cellular metabolic activity in an overnight assay.
      The antiviral potencies of other cardiac glycosides correlated with their
      potencies against the known target of these compounds, the cellular sodium
      potassium ATPase. Ouabain had a reduced effect if added 8 h post-infection. It
      did not inhibit viral attachment or entry, but did reduce the expression of viral
      immediate-early and early genes by at least 5-fold. Collectively, these results
      implicate a cellular target that was hitherto not considered important for a
      stage of HSV replication prior to viral gene expression.

PMID- 17544049
TI  - Packaged replicons of bovine viral diarrhea virus are capable of inducing a
      protective immune response.
AB  - Bovine viral diarrhea virus (BVDV) replicons with deletions within the capsid,
      E(RNS) or E1 encoding region were constructed and efficiently packaged with a
      helper cell line. High titres of packaged replicons were observed as early as 24
      h after transfection, whereas no virus progeny could be detected after
      transfection of non-complementing cells. Infection of bovine cell cultures with
      rescued viruses resulted in one cycle of replication without release of
      infectious virus particles, and no genetic reversion of the generated viruses was
      detected. Packaged replicons with a deletion within the capsid-coding region were
      characterized in vivo in immunization and challenge trials. Following
      immunization of calves with the replication-deficient virus, neither virus
      shedding nor viremia was detected. After challenge infection with virulent BVDV,
      all vaccinates were completely protected from disease as measured by the absence
      of viremia and shedding of challenge virus, which indicated that a 'sterilizing
      immunity' could be induced with the generated replication-deficient packaged
      replicons.

PMID- 17544050
TI  - Comparison of colorimetric and membrane introduction mass spectrometry techniques
      for chloramine analysis.
AB  - Three methods for the determination of chloramines in water were compared using
      pH-buffered nanopure water and natural organic matter (NOM) solutions. We
      investigated whether the N,N-diethyl-p-phenylenediamine (DPD) colorimetric method
      and/or an adapted indophenol method (Hach MonochlorF) are suitable for
      determining the concentration of monochloramine in drinking water. Membrane
      introduction mass spectrometry (MIMS) was used as a reference analysis method to
      determine the different chloramine species in water. All methods measured
      monochloramine accurately in Nanopure water, but the DPD colorimetric method
      measured higher residuals (inorganic and organic chloramines) than MonochlorF or
      MIMS when in the presence of NOM due to organic chloramines. The indophenol
      method (MonochlorF) accurately detected only monochloramine and not other
      chloramine forms. Overall, the monochloramine concentration measured by
      MonochlorF was comparable with the MIMS results. A combined chlorine residual
      approach by the DPD colorimetric method does not differentiate between
      monochloramine and organic chloramines. Therefore, DPD colorimetric methods can
      overestimate disinfection efficacy in chloraminated water systems because of
      interference from organic chloramines that have no or poor bactericidal ability.
      Compared with the DPD colorimetric method, MonochlorF is a better choice for
      chloraminated water systems.

PMID- 17544051
TI  - Confirmation of putative stormwater impact on water quality at a Florida beach by
      microbial source tracking methods and structure of indicator organism
      populations.
AB  - The effect of a stormwater conveyance system on indicator bacteria levels at a
      Florida beach was assessed using microbial source tracking methods, and by
      investigating indicator bacteria population structure in water and sediments.
      During a rain event, regulatory standards for both fecal coliforms and
      Enterococcus spp. were exceeded, contrasting with significantly lower levels
      under dry conditions. Indicator bacteria levels were high in sediments under all
      conditions. The involvement of human sewage in the contamination was investigated
      using polymerase chain reaction (PCR) assays for the esp gene of Enterococcus
      faecium and for the conserved T antigen of human polyomaviruses, all of which
      were negative. BOX-PCR subtyping of Escherichia coli and Enterococcus showed
      higher population diversity during the rain event; and higher population
      similarity during dry conditions, suggesting that without fresh inputs, only a
      subset of the population survives the selective pressure of the secondary
      habitat. These data indicate that high indicator bacteria levels were
      attributable to a stormwater system that acted as a reservoir and conduit,
      flushing high levels of indicator bacteria to the beach during a rain event. Such
      environmental reservoirs of indicator bacteria further complicate the already
      questionable relationship between indicator organisms and human pathogens, and
      call for a better understanding of the ecology, fate and persistence of indicator
      bacteria.

PMID- 17544052
TI  - Mineralization of C.I. Reactive Yellow 84 in aqueous solution by sonolytic
      ozonation.
AB  - The operational parameters and mechanism of mineralization of C.I. Reactive
      Yellow 84 (RY84), one of the azo dyes, in aqueous solution were investigated
      using sonolytic ozonation (US/O(3) oxidation). Of the pseudo-first-order
      degradation rate constants of TOC reduction, 9.0 x 10(-4), 7.3 x 10(-3) and 1.8 x
      10(-2)min(-1) were observed with US, O3, and a combination of US and O3,
      respectively. These results illustrate that ozonation combined with sonolysis for
      removal of TOC is more efficient than ozonation alone or ultrasonic irradiation
      alone without considering the operating costs. With the initial pH value at 10.0,
      the ozone dose at 4.5 g h(-1), the energy density of ultrasound at 176 W l(-1),
      and the initial concentration of RY84 at 100 mg l(-1), the extent of
      mineralization measured as TOC loss was maximized. The variation of the
      concentrations of related ions (oxalate, formate, acetate, NO3(-), NO2(-),
      NH4(+), Cl(-), and SO4(2-)) during the reaction process was monitored. Other
      organic intermediates detected by GC/MS were N-methyleneaniline, phthalic acid, 4
      hydroxyphthalic acid, isocyanatobenzene, aniline, 4-iminocyclohexa-2,5-dien-1
      one, butene diacid and urea. Based on these findings, a tentative degradation
      pathway was proposed.

PMID- 17544053
TI  - Immobilization of polyphenol oxidase onto mesoporous activated carbons --
      isotherm and kinetic studies.
AB  - Investigations were carried out in batch modes for studying the immobilization
      behavior of polyphenol oxidase (PPO) on two different mesoporous activated carbon
      matrices, MAC400 and MAC200. The PPO was immobilized onto MAC400 and MAC200 at
      various enzyme activities 5 x 10(4), 10 x 10(4), 20 x 10(4), 30 x 10(4)Ul(-1), at
      pH 5-8, and at temperature ranging from 10 to 40 degrees C. The intensity of
      immobilization of PPO increased with increase in temperature and initial
      activities, while it decreased with increase in pH. Immobilization onto MAC400
      followed the Langmuir model while Langmuir and Freundlich models could fit MAC200
      data. Non-linear pseudo first order, pseudo second order and intraparticle
      diffusion models were evaluated to understand the mechanism of immobilization.
      The free and immobilized enzyme kinetic parameters (K(m) and V(max)) were
      determined by Michaelis-Menten enzyme kinetics. The K(m) values for free enzyme,
      PPO immobilized in MAC400 and in MAC200 were 0.49, 0.41 and 0.65 mM,
      respectively. The immobilization of PPO in carbon matrices was confirmed using FT
      IR spectroscopy and scanning electron microscopy.

PMID- 17544054
TI  - Fungicide impacts on microbial communities in soils with contrasting management
      histories.
AB  - The impacts of the fungicides azoxystrobin, tebuconazole and chlorothalonil on
      microbial properties were investigated in soils with identical mineralogical
      composition, but possessing contrasting microbial populations and organic matter
      contents arising from different management histories. Degradation of all
      pesticides was fastest in the high OM/biomass soil, with tebuconazole the most
      persistent compound, and chlorothalonil the most readily degraded. Pesticide
      sorption distribution coefficient (K(d)) did not differ significantly between the
      soils. Chlorothalonil had the highest K(d) (97.3) but K(d) for azoxystrobin and
      tebuconazole were similar (13.9 and 12.4, respectively). None of the fungicides
      affected microbial biomass in either soil. However, all fungicides significantly
      reduced dehydrogenase activity to varying extents in the low OM/biomass soil, but
      not in the high OM/biomass soil. The mineralization of subsequent applications of
      herbicides, which represents a narrow niche soil process was generally reduced in
      both soils by azoxystrobin and chlorothalonil. 16S rRNA-PCR denaturing gradient
      gel electrophoresis (DGGE) indicated that none of the fungicides affected
      bacterial community structure. 18S rRNA PCR-DGGE analysis revealed that a small
      number of eukaryote bands were absent in certain fungicide treatments, with each
      band being specific to a single fungicide-soil combination. Sequencing indicated
      these represented protozoa and fungi. Impacts on the specific eukaryote DGGE
      bands showed no relationship to the extent to which pesticides impacted
      dehydrogenase or catabolism of herbicides.

PMID- 17544055
TI  - Total and inorganic arsenic in Antarctic macroalgae.
AB  - The Antarctic region offers unparalleled possibilities of investigating the
      natural distribution of metals and metalloids, such as arsenic. Total and
      inorganic As were analysed in nine species of Antarctic macroalgae collected
      during the 2002 summer season in the Potter Cove area at Jubany-Dallmann Station
      (South Shetland Islands, Argentinian Base). Total As was determined by
      inductively coupled plasma-optical emission spectrometry after microwave-assisted
      acid digestion. Inorganic As was determined by acid digestion, solvent
      extraction, flow injection-hydride generation-atomic absorption spectrometry.
      Total As ranged from 5.8 microg g(-1) dry weight (dw) (Myriogramme sp.) to 152
      microg g(-1)dw (Himantothallus grandifolius). Total As concentrations were higher
      in Phaeophytes (mean+/-SD: 71+/-44 microg g(-1)dw) than in Rhodophytes (mean+/
      SD: 15+/-11 microg g(-1)dw). Inorganic As ranged from 0.12 microg g(-1)
      (Myriogramme sp.) to 0.84 microg g(-1)dw (Phaeurus antarcticus). The percentage
      of inorganic As with respect to total As was 0.7 for Phaeophytes, but almost 4
      times higher for Rhodophytes (2.6). The work discusses possible causes for the
      presence of As in marine organisms in that pristine environment.

PMID- 17544056
TI  - Low auxotrophy-complementing amino acid concentrations reduce yeast chronological
      life span.
AB  - In the yeast Saccharomyces cerevisiae, interventions resembling caloric
      restriction, either by reduction of glucose or non-essential amino acid content
      in the medium, prolong life span and retard aging. Here we have examined the role
      of auxotrophy-complementing amino acid supplementation of S. cerevisiae strains
      in determining yeast chronological life span and stress resistance. The results
      obtained from cells cultured in standard amino acid concentrations revealed a
      reduced final biomass yield and premature aging phenotypes. These included
      shorter life span and indicators of oxidative stress, together with a G2/M cell
      cycle arrest and the appearance of a sub-G0/G1 population pointing to the
      occurrence of a specific cell death programme under starvation of essential amino
      acids. In order to overcome this starvation, five times higher amino acid
      concentrations were supplied to the medium as has already been commonly used by
      few laboratories. Such cultures reached more than five-fold higher final biomass
      yield in stationary phase and the early aging phenotypes were abrogated.
      Furthermore, in a long-lived yeast strain lacking TOR1, there was no positive
      effect of amino acid supplementation on longevity. On the contrary, amino acid
      supply had a positive effect on chronological life span of RAS2 deleted cells.
      This study may provide novel insights into the role of essential nutrients and
      their effect on aging process and raises the warning that the positive effects of
      caloric restriction on life span maybe restricted to non-essential nutrients.
      Moreover, the severe consequences on cell physiology, life span and stress
      resistance induced by essential amino acid imbalances presents a note of caution
      for those still using standard amino acid concentrations for studies with
      auxotrophic yeast strains.

PMID- 17544057
TI  - Separated components of root exudate and cytosol stimulate different
      morphologically identifiable types of branching responses by arbuscular
      mycorrhizal fungi.
AB  - Two morphologically distinct hyphal branching responses by the AM fungus, Glomus
      intraradices, were stimulated by separated components of carrot root exudate.
      Complex branching up to the sixth order was induced by compounds most soluble in
      35% methanol, whereas the formation of more lateral branches (second order) was
      stimulated by compounds most soluble in 70% methanol. This same 70% alcohol
      soluble fraction also stimulated a completely different type of branching pattern
      in another fungus, Gigaspora gigantea. This pattern consisted of a very periodic
      distribution of dense clusters of hyphal branches that had a very high degree of
      complexity. In contrast to exudate components, separated cytosolic components of
      carrot roots did not stimulate any of the observed hyphal branching patterns.
      Alcohol-soluble fractions actually inhibited hyphal tip growth of G. gigantea and
      induced the formation of "recovery" branches that were identical to those induced
      by an inhibitor found in the exudate of Chard (Beta vulgaris ssp. cicla), a non
      host plant.

PMID- 17544058
TI  - Predictors of urinary cadmium levels in adult females.
AB  - Ubiquitous exposure to low levels of cadmium has raised concern about adverse
      health effects. The aim of this study was to identify characteristics of non
      occupationally exposed adult females that correlated with creatinine-adjusted
      urinary cadmium levels. In our population-based study, trained interviewers
      collected information from 254 female Wisconsin residents aged 20-69 years on
      tobacco use, limited dietary consumption patterns, reproductive history,
      demographics, and residential history. Participants provided spot-urine specimens
      collected at home. Urine cadmium concentrations were quantified using inductively
      coupled plasma mass spectrometry and creatinine levels were also determined.
      Least square means and 95% confidence intervals for the natural log of the
      creatinine-adjusted urinary cadmium levels were calculated for each
      characteristic using multivariate analysis of variance adjusting for age and
      smoking status. Results were calculated on the log scale and then transformed to
      the original scale by taking the exponent of each of the values. We observed
      statistically significant increasing creatinine-adjusted urinary cadmium mean
      levels relative to smoking status, older age, parity, lower body surface area,
      mineral zinc supplement consumption, and high income. We did not observe a
      difference relative to consumption of organ meats, crustaceans, alcohol,
      multivitamins, multiminerals or homegrown vegetables, age of menopause, menarche
      of participant or oldest daughter, menopausal status or urban-rural residential
      location. Approximately 40% of the variance in creatinine-adjusted urinary
      cadmium levels in adult women was explained by several characteristics. Similar
      to other studies, age and smoking were the strongest determinants of creatinine
      adjusted urinary cadmium concentration.

PMID- 17544059
TI  - Long-term changes in mercury concentrations in fish from the middle Savannah
      River.
AB  - Total mercury levels were measured in largemouth bass (Micropterus salmoides),
      "sunfish" (Lepomis spp.), and "catfish" (primarily Ameiurus spp. and Ictalurus
      punctatus) from 1971 to 2004 in the middle Savannah River (river km 191 to 302),
      which drains the coastal plain of the southeastern U.S. Total mercury
      concentrations were higher in largemouth bass (overall mean of 0.55 mg/kg from
      1971 to 2004), a piscivorous (trophic level 4) species than in the other taxa
      (means of 0.22-0.26 mg/kg), but temporal trends were generally similar among
      taxa. Mercury levels were highest in 1971 but declined over the next 10 years due
      to the mitigation of point source industrial pollution. Mercury levels in fish
      began to increase in the 1980s as a likely consequence of mercury inputs from
      tributaries and associated wetlands where mercury concentrations were
      significantly elevated in water and fish. Mercury levels in Savannah River fish
      decreased sharply in 2001-2003 coincident with a severe drought in the Savannah
      River basin, but returned to previous levels in 2004 with the resumption of
      normal precipitation. Regression models showed that mercury levels in fish
      changed significantly over time and were affected by river discharge. Mercury
      levels in Savannah River fish were only slightly lower in 2004 (0.3 to 0.8 mg/kg)
      than in 1971 (0.4 to 1.0 mg/kg) despite temporal changes during the intervening
      years.

PMID- 17544065
TI  - Chronic stress: implications for neuronal morphology, function and neurogenesis.
AB  - In normal life, organisms are repeatedly exposed to brief periods of stress, most
      of which can be controlled and adequately dealt with. The presently available
      data indicate that such brief periods of stress have little influence on the
      shape of neurons or adult neurogenesis, yet change the physiological function of
      cells in two time-domains. Shortly after stress excitability in limbic areas is
      rapidly enhanced, but also in brainstem neurons which produce catecholamines;
      collectively, during this phase the stress hormones promote focused attention,
      alertness, vigilance and the initial steps in encoding of information linked to
      the event. Later on, when the hormone concentrations are back to their pre-stress
      level, gene-mediated actions by corticosteroids reverse and normalize the
      enhanced excitability, an adaptive response meant to curtail defense reactions
      against stressors and to enable further storage of relevant information. When
      stress is experienced repetitively in an uncontrollable and unpredictable manner,
      a cascade of processes in brain is started which eventually leads to profound,
      region-specific alterations in dendrite and spine morphology, to suppression of
      adult neurogenesis and to inappropriate functional responses to a brief stress
      exposure including a sensitized activation phase and inadequate normalization of
      brain activity. Although various compounds can effectively prevent these cellular
      changes by chronic stress, the exact mechanism by which the effects are
      accomplished is poorly understood. One of the challenges for future research is
      to link the cellular changes seen in animal models for chronic stress to
      behavioral effects and to understand the risks they can impose on humans for the
      precipitation of stress-related disorders.

PMID- 17544068
TI  - The patient safety in surgery study: background, study design, and patient
      populations.
AB  - BACKGROUND: The purpose of this article is to describe the background, design,
      and patient populations of the Patient Safety in Surgery Study, as a preliminary
      to the articles in this journal that will report the results of the Study. STUDY
      DESIGN: The Patient Safety in Surgery Study was a prospective cohort study.
      Trained nurses collected preoperative risk factors, operative variables, and 30
      day postoperative mortality and morbidity outcomes in patients undergoing major
      general and vascular operations at 128 Veterans Affairs (VA) medical centers and
      14 selected university medical centers between October 1, 2001 and September 30,
      2004. An Internet-based data collection system was used to input data from the
      different private medical centers. Semiannual feedback of observed to expected
      mortality and morbidity ratios was provided to the participating medical centers.
      RESULTS: During the 3-year study, total accrual in general surgery was 145,618
      patients, including 68.5% from the VA and 31.5% from the private sector. Accrual
      in vascular surgery totaled 39,225 patients, including 77.8% from the VA and
      22.2% from the private sector. VA patients were older and included a larger
      proportion of male patients and African Americans and Hispanics. The VA
      population included more inguinal, umbilical, and ventral hernia repairs,
      although the private-sector population included more thyroid and parathyroid,
      appendectomy, and operations for breast cancer. Preoperative comorbidities were
      similar in the two populations, but the rates of comorbidities were higher in the
      VA. American Society of Anesthesiologists classification tended to be higher in
      the VA. CONCLUSIONS: The National Surgical Quality Improvement Program
      methodology was successfully implemented in the 14 university medical centers.
      The data from the study provided the basis for the articles in this issue of the
      Journal of the American College of Surgeons.

PMID- 17544066
TI  - Chronic ethanol intake modulates photic and non-photic circadian phase responses
      in the Syrian hamster.
AB  - Chronic alcohol intake disrupts sleep and other circadian biological rhythms in
      both human alcoholics and in experimental animals. Recent studies from our
      laboratory indicate that these effects may be due, in part, to ethanol-induced
      alterations in fundamental properties of the circadian pacemaker. The present
      study explored the effects of chronic voluntary ethanol intake (25% v/v) on
      circadian phase responses to both photic and non-photic stimuli in Syrian
      hamsters. Hamsters were used in these experiments because they are a popular
      model organism in behavioral chronobiology research, and are characterized by
      unusually high levels of voluntary ethanol intake. Relative to controls, ethanol
      exposed animals showed attenuation of circadian phase responses and wheel running
      activity following acute administration of the benzodiazepine, triazolam, a non
      photic phase-shifting stimulus. In addition, ethanol-exposed animals displayed
      reduced phase advances, but normal phase delays, in response to brief light
      pulses. While the mechanisms underlying these effects remain to be elucidated, we
      hypothesize that ionotropic GABA and glutamate receptors may be involved, since
      these proteins serve as important targets for the neurobiological effects of
      ethanol, and are also known to be critically involved in the modulation of photic
      and non-photic circadian phase responses.

PMID- 17544069
TI  - Comparison of risk-adjusted 30-day postoperative mortality and morbidity in
      Department of Veterans Affairs hospitals and selected university medical centers:
      general surgical operations in men.
AB  - BACKGROUND: We used data from the Patient Safety in Surgery Study to compare
      patient populations, operative characteristics, and unadjusted and risk-adjusted
      30-day postoperative mortality and morbidity between the Veterans Affairs (VA) (n
      = 94,098) and private (n = 18,399) sectors for general surgery operations in men.
      STUDY DESIGN: This is a prospective cohort study. Trained nurses collected
      preoperative risk factors, operative variables, and 30-day postoperative
      mortality and morbidity outcomes in male patients undergoing major general
      surgery operations at 128 VA medical centers and 14 university medical centers
      from October 1, 2001, to September 30, 2004. Multiple logistic regression
      analysis was used to identify preoperative predictors of postoperative mortality
      and morbidity. An indicator variable for VA versus private-sector medical center
      was added to the model to determine if risk-adjusted outcomes were significantly
      different in the two systems. RESULTS: The unadjusted 30-day mortality rate was
      higher in the VA compared with the private sector (2.62% versus 2.03%, p =
      0.0002); unadjusted morbidity rate was lower in the VA compared with the private
      sector (12.24% versus 13.99%, p < 0.0001). After risk adjustment, odds ratio for
      mortality for the VA versus private sector was 1.23 (95% CI, 1.08-1.41). For
      morbidity after risk adjustment, the indicator variable for health-care system
      just missed statistical significance (p = 0.0585). Thirty-day postoperative
      mortality was comparable in the VA and private sector for very common operations
      but was higher in the VA for less common, more complex operations. CONCLUSIONS:
      In general surgery operations in men, the VA appeared to have a higher risk
      adjusted mortality rate compared with the private sector, but differences in
      mortality ascertainment in the two sectors might account for some of this effect.
      The higher mortality in the VA could be the result of higher mortality in the
      less common, more complex operations. There is a trend toward lower risk-adjusted
      morbidity in the VA compared with the private sector.

PMID- 17544070
TI  - Comparison of risk-adjusted 30-day postoperative mortality and morbidity in
      Department of Veterans Affairs hospitals and selected university medical centers:
      vascular surgical operations in men.
AB  - BACKGROUND: In response to a Congressional mandate to compare risk-adjusted
      surgical outcomes from Department of Veterans Affairs (VA) hospitals with those
      from private-sector hospitals, the National Surgical Quality Improvement Program
      was initiated in the VA system and then was developed in a select group of
      university medical centers in the private sector. This article analyzes risk
      adjusted outcomes after vascular surgical operations in men performed at VA
      hospitals as compared with private-sector hospitals. STUDY DESIGN: This is a
      prospective cohort study of a sample of vascular surgical operations in men
      performed at 128 VA medical centers as compared with 14 university medical
      centers from October 1, 2001 to September 30, 2004. Patient and operative
      characteristics, and both unadjusted and risk-adjusted 30-day postoperative
      morbidity and mortality outcomes were compared. RESULTS: Data from 30,058
      vascular operations in men at VA hospitals were compared with 5,174 cases
      performed at private-sector hospitals. The unadjusted 30-day mortality rate was
      notably lower in the VA system as compared with the private-sector group (3.4%
      versus 4.2%, p = 0.004). After risk-adjustment, there was no marked difference in
      mortality between the two hospital types. The unadjusted 30-day morbidity rate
      was also considerably lower in the VA hospitals as compared with the private
      sector (17.3% versus 22.3%, p < 0.0001). After risk-adjustment, morbidity in the
      VA system remained considerably lower than in the private sector, with an odds
      ratio of 0.84 (95% CI, 0.78 to 0.92). CONCLUSIONS: In vascular surgical
      operations in men, the VA hospitals demonstrated a lower risk-adjusted 30-day
      morbidity rate than the private-sector group. There is no marked difference in
      adjusted mortality rates between the two types of institutions.

PMID- 17544071
TI  - Comparison of risk-adjusted 30-day postoperative mortality and morbidity in
      Department of Veterans Affairs hospitals and selected university medical centers:
      general surgical operations in women.
AB  - BACKGROUND: In 1985, Congress mandated that the Department of Veterans Affairs
      (VA) compare its risk-adjusted surgical results with those in the private sector.
      The National Surgical Quality Improvement Program was developed as a result, in
      the VA system, and subsequently trialed in 14 university medical centers in the
      private sector. This report examines the results of the comparison between
      patient characteristics and outcomes of female general surgical patients in the
      two health care environments. STUDY DESIGN: Preoperative patient characteristics
      and laboratory variables, operative variables, and unadjusted postoperative
      outcomes were compared between VA and the private sector populations. In
      addition, stepwise logistic regression models were developed for 30-day
      postoperative mortality and morbidity. Finally, the effect of being treated in a
      VA or private sector hospital was assessed by adding an indicator variable to the
      models and testing it for statistical significance. RESULTS: Data from 5,157
      female general surgical VA patients who underwent eligible procedures were
      compared with those from 27,467 patients in the private sector. Unadjusted 30-day
      mortality was virtually identical in the two groups (1.3%). The unadjusted
      morbidity rate was slightly, but notably, higher in the private sector (10.9%) as
      compared with that observed in the VA (8.5%, p < 0.0001). Predictive models were
      generated for mortality and morbidity combining both groups; top variables in
      these models were similar to those described previously in the National Surgical
      Quality Improvement Program. The indicator variable for system of care (VA versus
      private sector) was not statistically significant in the mortality model, but
      substantially favored the VA in the morbidity model (odds ratio=0.80, 95%
      CI=0.71, 0.90). CONCLUSIONS: The data demonstrate that in female general surgical
      patients, risk-adjusted mortality rates are comparable in the VA and the private
      sector, but risk-adjusted morbidity is higher in the private sector. Rates of
      urinary tract infections in the two populations may account for much of the
      latter difference.

PMID- 17544072
TI  - Comparison of risk-adjusted 30-day postoperative mortality and morbidity in
      Department of Veterans Affairs hospitals and selected university medical centers:
      vascular surgical operations in women.
AB  - BACKGROUND: Women with peripheral vascular disease requiring vascular operations
      are less well studied than their male counterparts. The surgical outcomes of
      female vascular patients in the Department of Veterans Affairs (VA) and private
      sector hospitals have not previously been compared, and their preoperative risk
      profile, postoperative morbidity, and mortality need to be better elucidated.
      STUDY DESIGN: Patients undergoing vascular operations at 14 private sector and
      128 VA hospitals, from October 2001 through September 2004, had their
      preoperative characteristics, operative data, and 30-day postoperative morbidity
      and mortality compared, as part of the Patient Safety in Surgery (PSS) Study.
      Logistic regression analysis was performed to develop predictive models for
      morbidity and mortality, which allowed for a comparison of risk-adjusted outcomes
      between the two hospital groups. RESULTS: There were 458 vascular surgical
      operations performed in women in the VA, and 3,535 vascular operations were
      performed in women in the private sector. Eighteen of 45 preoperative
      comorbidities and laboratory variables differed considerably between the
      institutions, and 16 of 18 were adverse among the private sector patients. The
      unadjusted 30-day mortality rate was higher in the private sector compared with
      the VA (5.2% versus 2.4%, p=0.008); the unadjusted morbidity rate was higher in
      the private sector compared with the VA sector (23.4% versus 13.3%, p < 0.0001).
      After risk adjustment, there was no marked difference between the VA and the
      private sector in mortality (p=0.12), but the difference in morbidity rates
      remained pronounced, with an odds ratio of 0.60 for VA versus private sector (95%
      CI=0.44, 0.81). CONCLUSIONS: Compared with their VA counterparts, women
      undergoing vascular operations at private sector hospitals had a higher incidence
      of preoperative comorbidities; after risk adjustment, mortality did not differ
      substantially. Despite risk adjustment, the incidence of postoperative morbidity
      in the VA patients was considerably lower, suggesting unidentified differences in
      the hospital populations, their processes of care, or both.

PMID- 17544073
TI  - Relationship of processes and structures of care in general surgery to
      postoperative outcomes: a qualitative analysis.
AB  - BACKGROUND: With increased focus on improving surgical care quality,
      understanding structures and processes that influence surgical care is timely and
      important, as is more precise specification of these through improved
      measurement. STUDY DESIGN: We conducted a qualitative study to help design a
      quantitative survey of structures and processes of surgical care. We audiotaped
      44 face-to-face interviews with surgical care leaders and other diverse members
      of the surgical care team from 6 hospitals (two Veterans Affairs, four private
      sector). Qualitative interviews were transcribed and analyzed to identify common
      structures and processes mentioned by interviewees to include on a quantitative
      survey and to develop a rich description of salient themes on indicators of
      effective surgical care services and surgical care teams. RESULTS: Qualitative
      analyses of transcripts resulted in detailed descriptions of structures and
      processes of surgical care services that affected surgical care team performance-
      and how particular structures led to effective and ineffective processes that
      impacted quality and outcomes of surgical care. Communication and care
      coordination were most frequently mentioned as essential to effective surgical
      care services and teams. Informants also described other influences on surgical
      quality and outcomes, such as staffing, the role of residents, and team
      composition and continuity. CONCLUSIONS: Surgical care team members reinforced
      the importance of understanding surgical care processes and structures to improve
      both quality and outcomes of surgical care. The analysis of interviews helped the
      study team identify potential measures of structures and processes to include in
      our quantitative survey.

PMID- 17544074
TI  - Relationship of processes and structures of care in general surgery to
      postoperative outcomes: a descriptive analysis.
AB  - BACKGROUND: The systematic collection of quantitative data on structures and
      processes from surgical services participating in the National Surgical Quality
      Improvement Program (NSQIP) has not been a focus to date. Efficient collection of
      useful measures of structures and processes may improve understanding of surgical
      outcomes and strategies for improving the quality of surgical care, as NSQIP
      continues to expand. The purpose of this article was to describe results of a
      quantitative survey designed to measure surgical care structures and processes
      within NSQIP sites. STUDY DESIGN: A cross-sectional survey was mailed to 123
      Department of Veteran Affairs (VA) and 14 private sector sites participating in
      the Agency for Healthcare Research and Quality (AHRQ)-funded Patient Safety in
      Surgery (PSS) Study. The survey included questions about organizational
      structures and processes of preoperative, intraoperative, and postoperative
      general surgical care services. For this study, we included only data from 90 VA
      sites that returned a survey (73% response rate). We used descriptive statistics
      and examined the bivariate association of structures and processes items or
      scales with risk-adjusted observed-to-expected (O/E) ratios of surgical morbidity
      and mortality. RESULTS: Examination of frequency or means and standard deviations
      of items and scales revealed substantial variation in the structures and
      processes of surgical care services in participating VA sites, with correlation
      analyses demonstrating that, of 35 process and structure variables, there was a
      statistically significant relationship with the hospital's observed-to-expected
      ratio for 14 variables for morbidity, but only 4 variables for mortality.
      CONCLUSIONS: This descriptive analysis provides support for the potential
      importance of measuring organizational structures and processes of care in
      addition to risk-adjusted morbidity and mortality.

PMID- 17544075
TI  - Relationship of processes and structures of care in general surgery to
      postoperative outcomes: a hierarchical analysis.
AB  - BACKGROUND: The majority of studies relating processes and structures of surgical
      care to outcomes focus on mortality alone, even though morbidity outcomes are
      frequent, costly, and can have an adverse effect on a patient's short- and
      longterm survival and quality of life. The purpose of this study was to identify
      the important processes and structures of surgical care that relate to 30-day,
      risk-adjusted postoperative morbidity in general surgery. STUDY DESIGN:
      Department of Veterans Affairs general surgery patients operated on in the period
      October 1, 2003 to September 30, 2004 at medical centers that participated in the
      Patient Safety in Surgery (PSS) Study and responded to a process and structure of
      care survey were included in this study. The patient's risk information was
      combined with key process and structure variables in a hierarchical maximum
      likelihood analysis to predict 30-day postoperative morbidity. RESULTS: A number
      of hospital-level processes and structures of care were identified that predicted
      30-day postoperative morbidity. The dominant factor was university affiliation.
      Affiliated hospitals showed an increase in risk of morbidity even after
      adjustment for patient risk. CONCLUSIONS: Risk-adjusted morbidity is higher in
      Veterans Affairs hospitals that are affiliated with university medical centers.
      These findings mandate additional study to identify the exact factors responsible
      for this increased morbidity.

PMID- 17544076
TI  - Multivariable predictors of postoperative surgical site infection after general
      and vascular surgery: results from the patient safety in surgery study.
AB  - BACKGROUND: Surgical site infection (SSI) is a potentially preventable
      complication. We developed and tested a model to predict patients at high risk
      for surgical site infection. STUDY DESIGN: Data from the Patient Safety in
      Surgery Study/National Surgical Quality Improvement Program from a 3-year period
      were used to develop and test a predictive model of SSI using logistic regression
      analyses. RESULTS: From October 2001 through September 2004, 7,035 of 163,624
      (4.30%) patients undergoing vascular and general surgical procedures at 14
      academic and 128 Department of Veterans Affairs (VA) medical centers experienced
      SSI. Fourteen variables independently associated with increased risk of SSI
      included patient factors (age greater than 40 years, diabetes, dyspnea, use of
      steroids, alcoholism, smoking, recent radiotherapy, and American Society of
      Anesthesiologists class 2 or higher), preoperative laboratory values (albumin<3.5
      mg/dL, total bilirubin>1.0 mg/dL), and operative characteristics (emergency,
      complexity [work relative value units>/=10], type of procedure, and wound
      classification). The SSI risk score is more accurate than the National Nosocomial
      Infection Surveillance score in predicting SSI (c-indices 0.70, 0.62,
      respectively). CONCLUSIONS: We developed and tested an accurate prediction score
      for SSI. Clinicians can use this score to predict their patient's risk of an SSI
      and implement appropriate prevention strategies.

PMID- 17544077
TI  - Multivariable predictors of postoperative respiratory failure after general and
      vascular surgery: results from the patient safety in surgery study.
AB  - BACKGROUND: Postoperative respiratory failure (RF) is associated with an increase
      in hospital morbidity, mortality, cost, and late mortality. We developed and
      tested a model to predict the risk of postoperative RF in patients undergoing
      major vascular and general surgical operations. This model is an extension of an
      earlier model that was derived and tested exclusively from a population of male
      patients from the Veterans Affairs National Surgical Quality Improvement Program.
      METHODS: Patients undergoing vascular and general surgical procedures at 14
      academic and 128 Veterans Affairs Medical Centers from October 2001 through
      September 2004 were used to develop and test a predictive model of postoperative
      RF using logistic regression analyses. RF was defined as postoperative mechanical
      ventilation for longer than 48 hours or unanticipated reintubation. RESULTS: Of
      180,359 patients, 5,389 (3.0%) experienced postoperative RF. Twenty-eight
      variables were found to be independently associated with RF. Current procedural
      terminology group, patients with a higher American Society of Anesthesiologists
      classification, emergency operations, more complex operation (work relative value
      units), preoperative sepsis, and elevated creatinine were more likely to
      experience RF. Older patients, male patients, smokers, and those with a history
      of congestive heart failure or COPD, or both, were also predisposed. The model's
      discrimination (c-statistic) was excellent, with no decrement from development
      (0.856) to validation (0.863) samples. CONCLUSIONS: This model updates a
      previously validated one and is more broadly applicable. Its use to predict
      postoperative RF risk enables the study of preventative measures or preoperative
      risk adjustment and intervention to improve outcomes.

PMID- 17544078
TI  - Multivariable predictors of postoperative cardiac adverse events after general
      and vascular surgery: results from the patient safety in surgery study.
AB  - BACKGROUND: Cardiac adverse events (CAEs) are relatively infrequent, but highly
      lethal, after noncardiac operations. The value of available risk scoring systems
      is uncertain and these systems can be outdated. We used the Patient Safety in
      Surgery Study database to develop and test a model to predict patient risk for
      CAEs after general and vascular surgical operations. STUDY DESIGN: As part of the
      Patient Safety in Surgery Study, following the National Surgical Quality
      Improvement Program's protocol, multiple demographic, preoperative,
      perioperative, and outcomes variables were measured during a 3-year period. Data
      from 128 Veterans Affairs medical center hospitals and from 14 academic medical
      centers on 183,069 patients were used in a logistic regression analysis to model
      multivariable predictors of serious CAEs (cardiac arrest or acute myocardial
      infarction within 30 days of operation). RESULTS: CAEs occurred in 2,362 patients
      (1.29%) and of these, 59.44% expired. Multivariable stepwise logistic regression
      identified 20 independent predictors of CAEs, which excluded most cardiac
      specific risk factors. The most important multivariable predictors of CAE were
      American Society of Anesthesiologists physical status classification, work
      relative value units of the most complex procedure, age, and type of operation. A
      risk prediction scoring system using the logistic regression odds ratios proved
      to be a useful prediction tool when tested using a random sample from the
      database. CONCLUSIONS: CAEs after noncardiac operations are relatively infrequent
      but highly lethal. Operation type and urgency and American Society of
      Anesthesiologists physical status assessment are important independent predictors
      of cardiac morbidity, but angina, recent MI, and earlier cardiac operation are
      not. A prediction scoring system based on the Patient Safety in Surgery Study
      multivariable odds ratios is likely to be predictive of future events in a
      similar population requiring noncardiac procedures. This risk model can also
      serve as a tool to measure quality and effectiveness of care by providers who
      perform noncardiac operations.

PMID- 17544079
TI  - Multivariable predictors of postoperative venous thromboembolic events after
      general and vascular surgery: results from the patient safety in surgery study.
AB  - BACKGROUND: Venous thromboembolism (VTE) is a potentially preventable
      postoperative complication. Accurate risk prediction is an essential first step
      toward limiting serious, and sometimes fatal, postoperative VTE. We sought to
      develop and test a model to predict patients at high risk for postoperative VTE.
      STUDY DESIGN: Data from the Patient Safety in Surgery (PSS) Study were used to
      develop and test a predictive model of VTE using multiple logistic regression
      analyses. RESULTS: VTE occurred in 1,162 of 183,069 (0.63%) patients undergoing
      vascular and general surgical procedures. The 30-day mortality in patients who
      suffered a VTE was 11.19%. Fifteen variables independently associated with
      increased risk of VTE included patient factors (female gender, higher American
      Society of Anesthesiologists class, ventilator dependence, preoperative dyspnea,
      disseminated cancer, chemotherapy within 30 days, and > 4 U packed red blood cell
      transfusion in the 72 hours before operation), preoperative laboratory values
      (albumin < 3.5 mg/dL, bilirubin > 1.0 mg/dL, sodium > 145 mmol/L, and hematocrit
      < 38%), and operative characteristics (type of surgical procedure, emergency
      operation, work relative value units, and infected/contaminated wounds). These
      variables were used to develop a predictive model for postoperative VTE (c-index
      = 0.7647) and a risk score that can be used in the preoperative assessment of
      patients undergoing major operations. CONCLUSIONS: Venous thromboembolic events
      after noncardiac operations are relatively infrequent but highly lethal.
      Important multivariable risk factors for VTE in this setting were identified in
      the large PSS database. The risk-prediction scoring system, developed by using
      the logistic regression odds ratios, helps to identify patients at risk for
      postoperative VTE and to institute appropriate perioperative prophylactic
      measures.

PMID- 17544080
TI  - Thyroid and parathyroid operations in veterans affairs and selected university
      medical centers: results of the patient safety in surgery study.
AB  - BACKGROUND: There is increasing interest in surgical outcomes. The Patient Safety
      in Surgery (PSS) Study database was examined about thyroid and parathyroid
      procedures to determine risk factors for adverse outcomes and outcomes rates.
      Relative outcomes performance for the Veterans Affairs (VA) and private-sector
      populations was compared after risk adjustment. STUDY DESIGN: Preoperative,
      operative, and postoperative data were analyzed for 7,082 patients: 2,814 VA
      patients and 4,268 private sector patients. Prevalence of risk or process factors
      was described. Occurrence rates and unadjusted odds ratios (OR) for adverse
      outcomes were calculated. Stepwise multiple logistic regressions were performed
      to model the impact of various factors on outcomes and to calculate the adjusted
      OR for any adverse event for the VA population compared with the private sector.
      RESULTS: Overall mortality rate was 0.35% and 0.60% in the VA and 0.19% in the
      private sector. Overall rate of any adverse outcomes was 2.90% and 4.48% in the
      VA and 1.97% in the private sector. Adjusted OR for thyroid versus parathyroid
      operation was 0.94 (95% CI, 0.67-1.31). Adjusted OR for operation in the VA
      versus private sector was 1.25 (95% CI, 0.87-1.78). CONCLUSIONS: Overall rates of
      mortality and any morbidity were low and consistent with previous reports. Based
      on adjusted OR, there was no significant difference in outcomes for thyroid
      versus parathyroid operation. Similarly, there was no apparent significant
      difference in surgical outcomes between the VA and private-sector groups after
      risk adjustment.

PMID- 17544081
TI  - Breast cancer surgery in Veterans Affairs and selected university medical
      centers: results of the patient safety in surgery study.
AB  - BACKGROUND: Breast cancer is a common diagnosis. We compare perioperative
      characteristics and outcomes between male and female patients undergoing
      treatment for breast cancer and between hospital systems (Department of Veterans
      Affairs [VA] and private sector [PS]) as part of the Patient Safety in Surgery
      (PSS) Study. STUDY DESIGN: We performed an analysis of a prospectively collected
      clinical database. Data collected from 128 VA hospitals and 14 PS academic
      medical centers as part of the Patient Safety in Surgery Study for fiscal years
      2002 through 2004 were used. Analysis included calculation of crude and adjusted
      odds ratios for morbidity. RESULTS: A total of 3,823 patients were included.
      Female VA patients at baseline had higher rates of smoking, steroid use, COPD,
      acute renal failure, dialysis, weight loss > 10%, preoperative chemotherapy, and
      abnormal laboratory values than female PS patients did. Male patients were older
      than the female patients in both hospital systems. Mortality rates were very low
      and similar among groups. All VA patients in this study had substantially longer
      lengths of stay than the patients in the PS. The unadjusted overall complication
      rate was 5.21%; the VA female patients experienced an unadjusted complication
      rate twice that of the PS female patients. When adjusted for confounding
      variables and differences in preoperative comorbidities, the odds ratio comparing
      VA with PS females was no longer markedly different (1.404; 95% CI, 0.894,
      2.204). CONCLUSIONS: VA patients with breast cancer have higher incidences of
      most comorbidities than patients in the PS. Differences in complication rates
      females disappear when adjustment is made for the higher rates of comorbidities
      in the VA patients.

PMID- 17544082
TI  - Liver resection in veterans affairs and selected university medical centers:
      results of the patient safety in surgery study.
AB  - BACKGROUND: A congressional mandate, which led to the formation of the National
      Surgical Quality Improvement Program, is now being fulfilled with the publication
      of general and vascular surgical outcomes comparisons between Veterans Affairs
      (VA) and university medical centers. A series of National Surgical Quality
      Improvement Program articles evaluate the effect of hospital type (VA versus
      university hospitals) on procedure-specific outcomes. This article focuses on
      liver resections. STUDY DESIGN: This is a prospective cohort study of a sample of
      patients undergoing liver resections at 128 VA medical centers compared with 14
      university medical centers from October 1, 2001, to September 30, 2004.
      Preoperative and intraoperative characteristics were evaluated to identify
      possible variables related to morbidity and mortality and possible confounders of
      the hospital effect. These variables were then used to identify the effect that
      the hospital setting might have on surgical outcomes after liver resections.
      RESULTS: Data from 237 liver resections at VA hospitals were compared with 783
      procedures performed at university hospitals. The unadjusted 30-day morbidity
      rate tended to be higher in the VA (university 22.6% versus VA 27.9%; p = 0.10).
      After risk adjustment, results were equivalent (odds ratio = 0.94; p = 0.77).
      Unadjusted 30-day mortality rate was significantly higher in VA hospitals (6.8%
      versus 2.6%; p = 0.002). After risk adjustment, there was no longer a significant
      difference in mortality between the two hospital systems (odds ratio = 1.62; p =
      0.33). CONCLUSIONS: For liver resections, the National Surgical Quality
      Improvement Program and Patient Safety in Surgery Study data suggest that there
      is no significant difference in risk-adjusted morbidity or mortality rates
      between VA and the university medical centers.

PMID- 17544083
TI  - Pancreatic resection in Veterans Affairs and selected university medical centers:
      results of the patient safety in surgery study.
AB  - BACKGROUND: Pancreatectomy is a high-risk, technically demanding operation
      associated with substantial perioperative morbidity and mortality. This study
      aims to describe the 30-day morbidity and mortality for pancreatectomy and to
      compare outcomes between private-sector and Veterans Affairs hospitals using
      multiinstitutional data. STUDY DESIGN: This is a retrospective review of patients
      who underwent pancreatic resection for neoplasia at private-sector (PS) and
      Veterans Affairs (VA) hospitals participating in the National Surgical Quality
      Improvement Program Patient Safety in Surgery Study in fiscal years 2002 to 2004.
      The variables reviewed were demographics, preoperative medical conditions,
      intraoperative variables, and outcomes. Using logistic regression to control for
      differences in patient comorbidities, 30-day mortality and morbidity rates
      between PS and VA hospitals were compared. RESULTS: A total of 1,069 patients
      underwent pancreatectomy for neoplasia at 97 participating hospitals. Six hundred
      ninety-two patients were treated at PS hospitals and 377 at VA hospitals. The
      average number of patients treated at each hospital was 11.0, with a range of 1
      to 83 during the 3-year study period. There were 842 patients who underwent
      pancreaticoduodenectomy (CPT 4815x) and 227 who underwent distal/subtotal
      pancreatectomy (CPT 4814x). Significant differences were observed between PS
      patients and VA patients with regard to comorbidities and patient demographics.
      The 30-day unadjusted morbidity rate was 33.8% overall, 42.2% at VA hospitals
      versus 29.1% at PS hospitals (p < 0.0001). Unadjusted and adjusted odds ratio
      (OR) for postoperative morbidity comparing VA with PS hospitals was 1.781 (95%
      CI, 1.369-2.318) and 1.581 (95% CI, 1.064-2.307). The 30-day unadjusted operative
      mortality rate was 3.8% overall, 6.4% at VA hospitals and 2.5% at PS hospitals (p
      = 0.0015). Unadjusted and adjusted OR for postoperative mortality was 2.909 (95%
      CI, 1.525-5.549) and 2.533 (95% CI, 1.020-6.290), respectively. Similar outcomes
      were observed when looking at pancreaticoduodenectomy (CPT 4815x) when analyzed
      independent of other types of pancreatic resections. CONCLUSION: Pancreatectomies
      are high-risk operations with substantial perioperative morbidity and mortality.
      Risk-adjusted outcomes for patients treated at PS hospitals were found to be
      superior to those for patients treated at VA hospitals in the study.

PMID- 17544084
TI  - Bariatric operations in Veterans Affairs and selected university medical centers:
      results of the patient safety in surgery study.
AB  - BACKGROUND: The objectives of this study were to evaluate outcomes and predictors
      of morbidity in patients undergoing Roux-en-Y gastric bypass (RYGB) during the
      Patient Safety in Surgery (PSS) Study. STUDY DESIGN: National Surgical Quality
      Improvement Program data on PSS patients undergoing RYGB were analyzed for
      unadjusted and adjusted outcomes. Gender groups acted differently and were
      analyzed separately. Multivariable regression modeling was used to analyze
      hospital type as a predictor of risk. Stepwise logistic regression was performed
      to determine patient factors predictive of postoperative morbidity. RESULTS: A
      total of 2,438 patients (2,064 private sector [PS], 374 Veterans Affairs [VA])
      were identified for analysis. Adjusted odds ratio for postoperative morbidity for
      VA versus PS female patients was 1.14 (95% CI, 0.63-2.05), and for male patients
      2.29 (95% CI, 1.28-4.10). Stepwise logistic regression showed that independent
      risk factors predictive of morbidity were open procedure, higher American Society
      of Anesthesiologists class, higher body mass index, diabetes, alcohol
      consumption, leukocytosis, SGOT > 40 U/L, smoking history, and older age.
      Importantly, male gender was not significant (p = 0.13) in the regression
      analysis. Subsequent and unrelated to this study, the VA has restructured its
      bariatric surgical program, including regionalization of centers, with a
      substantial lowering of associated mortality and morbidity. CONCLUSIONS: The VA
      male subset showed higher risk-adjusted postoperative morbidity compared with the
      PS male subset. The VA and PS female subsets had equivalent risk-adjusted
      postoperative morbidity. A systematic approach to quality-improvement processes
      resulted in improved bariatric surgical outcomes in the VA. Male gender might not
      be an independent risk factor in RYGB patients.

PMID- 17544085
TI  - Adrenalectomy in Veterans Affairs and selected university medical centers:
      results of the patient safety in surgery study.
AB  - BACKGROUND: Data from the Patient Safety in Surgery Study were used to compare
      preoperative risk factors, intraoperative variables, and surgical outcomes of
      adrenalectomy procedures performed in 81 Veterans Affairs (VA) hospitals with
      those performed in 14 private-sector (PS) hospitals. STUDY DESIGN: This study is
      a retrospective review of prospectively collected data on all patients undergoing
      adrenalectomy in the VA and PS for fiscal years 2002 through 2004. Bivariate
      analysis compared VA and PS preoperative risk factors, intraoperative variables,
      and 30-day morbidity and mortality. Regression risk-adjustment analysis was used
      to compare 30-day postoperative morbidity in the VA and PS. RESULTS: During the 3
      years studied, 178 VA patients and 371 PS patients underwent adrenalectomy
      procedures with a median per site of 2 (range 1-9) and 21 (range 8-70) procedures
      per VA and PS hospital, respectively. The VA patients had considerably more
      comorbidities than PS patients. The unadjusted 30-day morbidity rate was
      significantly higher in VA (16.29%) than PS (6.74%) hospitals (p = 0.0003); after
      controlling for the higher rate of comorbidities, the adjusted odds ratio for
      morbidity in the VA versus the PS hospitals was no longer significant (odds ratio
      = 1.328; 95% CI, 0.488-3.613). Unadjusted mortality rate was VA 2.81%, PS 0.27%,
      p = 0.0074. The low event rate overall precluded risk adjustment for mortality.
      CONCLUSIONS: The VA adrenalectomy population has more preoperative risk factors
      and substantially higher unadjusted 30-day postoperative morbidity and mortality
      rates than the PS population. After risk adjustment, there is no significant
      difference in morbidity between the VA and the PS. A larger study population is
      needed to compare risk-adjusted mortality between the VA and PS.

PMID- 17544086
TI  - Morbidity and mortality after liver resection: results of the patient safety in
      surgery study.
AB  - BACKGROUND: Liver resection is performed with increasing frequency. Nearly all of
      the published information on operative mortality and morbidity rates associated
      with liver resection is derived from studies that rely on retrospective data
      collection from single centers. The goal of this study is to use audited
      multiinstitutional data from the private sector of the Patient Safety in Surgery
      Study to characterize complications after liver resection and to identify
      variables that are associated with 30-day morbidity and mortality. STUDY DESIGN:
      Prospectively collected data on liver resection patients from 14 hospitals were
      collected using National Surgical Quality Improvement Program's methodology.
      Rates of occurrence of 21 defined postoperative complications were measured.
      Bivariate analyses and stepwise logistic regression were used to identify factors
      associated with 30-day morbidity and mortality. RESULTS: At least one
      complication occurred in 22.6% of patients within 30 days. Stepwise logistic
      regression identified several preoperative factors associated with morbidity,
      including serum albumin, SGOT > 40, previous cardiac operation, operative work
      relative value unit, and history of severe COPD. Mortality within 30 days was
      observed in 2.6% of patients. Factors associated with mortality were found to be
      male gender, American Society of Anesthesiologists class 3 or higher, presence of
      ascites, dyspnea, and severe COPD. Only 0.7% of patients without any
      complications died, compared with 9.0% of patients with at least 1 complication
      (p < 0.0001). CONCLUSIONS: Prospective, standardized, audited, multiinstitutional
      data were analyzed to identify several preoperative and intraoperative factors
      associated with morbidity and mortality after liver resection. These factors
      should be considered during patient selection and perioperative management.

PMID- 17544087
TI  - Use of national surgical quality improvement program data as a catalyst for
      quality improvement.
AB  - BACKGROUND: Semiannually, the National Surgical Quality Improvement Program
      (NSQIP) provides its participating sites with observed-to-expected (O/E) ratios
      for 30-day postoperative mortality and morbidity. At each reporting period, there
      is typically a small group of hospitals with statistically significantly high O/E
      ratios, meaning that their patients have experienced more adverse events than
      would be expected on the basis of the population characteristics. An important
      issue is to determine which actions a surgical service should take in the
      presence of a high O/E ratio. STUDY DESIGN: This article reviews case studies of
      how some of the Department of Veterans Affairs and private-sector NSQIP
      participating sites used the clinically rich NSQIP database for local quality
      improvement efforts. Data on postoperative adverse events before and after these
      local quality improvement efforts are presented. RESULTS: After local quality
      improvement efforts, wound complication rates were reduced at the Salt Lake City
      Veterans Affairs medical center by 47%, surgical site infections in patients
      undergoing intraabdominal surgery were reduced at the University of Virginia by
      36%, and urinary tract infections in vascular patients were reduced at the
      Massachusetts General Hospital by 74%. At some sites participating in the NSQIP,
      notably the Massachusetts General Hospital and the University of Virginia, the
      NSQIP has served as the basis for surgical service-wide outcomes research and
      quality improvement programs. CONCLUSIONS: The NSQIP not only provides
      participating sites with risk-adjusted surgical mortality and morbidity outcomes
      semiannually, but the clinically rich NSQIP database can also serve as a catalyst
      for local quality improvement programs to significantly reduce postoperative
      adverse event rates.

PMID- 17544092
TI  - Cellular and humoral aberrations in a kindred with IL-1 receptor-associated
      kinase 4 deficiency.

PMID- 17544093
TI  - BCG-osis and tuberculosis in a child with chronic granulomatous disease.
AB  - A few known primary immunodeficiencies confer predisposition to clinical disease
      caused by weakly virulent mycobacteria, such as BCG vaccines (regional disease,
      known as BCG-itis, or disseminated disease, known as BCG-osis), or more virulent
      mycobacteria, such as Mycobacterium tuberculosis (pulmonary and disseminated
      tuberculosis). We investigated the clinical and genetic features of a 12-year-old
      boy with both recurrent BCG-osis and disseminated tuberculosis. The patient's
      phagocytic cells produced no O(2)(-). A hemizygous splice mutation was found in
      intron 5 of CYBB, leading to a diagnosis of X-linked chronic granulomatous
      disease. Chronic granulomatous disease should be suspected in all children with
      BCG-osis, even in the absence of nonmycobacterial infectious diseases, and in
      selected children with recurrent BCG-itis or severe tuberculosis.

PMID- 17544094
TI  - Irritant skin test reactions to common vaccines.

PMID- 17544095
TI  - Successful treatment of cutaneous mastocytosis and Meniere disease with anti-IgE
      therapy.

PMID- 17544096
TI  - Probiotics for the prevention or treatment of allergic diseases.
AB  - This review addresses the effects of probiotic bacteria on immune development and
      the role in the treatment and prevention of allergic disease. Although there is a
      sound theoretical basis for anticipating benefits, there are currently
      insufficient data to recommend probiotics as a part of standard therapy in any
      allergic conditions. Furthermore, although there have been several studies to
      show a benefit in prevention of atopic eczema, other studies have failed to
      support this. None of the studies has shown any clear preventive effect on
      sensitization, nor any allergic disease other than eczema. The term "probiotic"
      is often used loosely to include bacterial strains with little documented
      immunomodulatory capacity or controlled studies to support the claims. It is not
      known whether effects in experimental systems have any clinical relevance.
      Finally, very little is known about this large, complex internal ecosystem.
      Explanations for the varied results between studies include host factors
      (including genetic differences in microbial responses and allergic
      predisposition) and other environmental factors, such as general microbial
      burden, individual microbiota, diet (including consumption of prebiotic
      substances), and treatment with antibiotics. As more studies are completed, these
      factors are likely to make robust meta-analyses problematic to perform.

PMID- 17544097
TI  - Consumer attitudes and risks associated with packaged foods having advisory
      labeling regarding the presence of peanuts.
AB  - BACKGROUND: Foods with advisory labeling (eg, "may contain") are increasingly
      prevalent. Consumers with food allergies might ignore advisory labeling advice.
      OBJECTIVE: We sought to determine whether consumers with food allergy heeded
      advisory labels and whether products with advisory labels contained detectable
      peanut allergen. METHODS: Surveys (n = 625 in 2003 and n = 645 in 2006) were
      conducted at Food Allergy & Anaphylaxis Network patient conferences. Food
      products bearing advisory statements regarding peanuts were analyzed for the
      presence of peanut. RESULTS: Consumers were less likely to heed advisory labeling
      in 2006 (75%) compared with in 2003 (85%, P < .01); behavior varied significantly
      according to the form of the statement. Peanut protein was detected in 10%
      (20/200) of total food products bearing advisory statements, although clinically
      significant levels of peanut (>1 mg of peanut or >0.25 mg of peanut protein) were
      detected in only 13 of 200 such products. CONCLUSION: Consumers with food allergy
      are increasingly ignoring advisory labeling. Because food products with advisory
      labeling do contain detectable levels of peanuts, a risk exists to consumers
      choosing to eat such foods. The format of the labeling statement did not
      influence the likelihood of finding detectable peanut, except for products
      listing peanuts as a minor ingredient, but did influence the choices of consumers
      with food allergy. CLINICAL IMPLICATIONS: Allergic patients are taking risks by
      increasingly disregarding advisory labeling.

PMID- 17544098
TI  - A new mechanism regulating the initiation of allergic airway inflammation.
AB  - BACKGROUND: The earliest immune events induced by allergens are poorly
      understood, yet are likely essential to understanding how allergic inflammation
      is established. OBJECTIVE: We sought to describe the earliest signaling events
      activated by allergen and determine their significance to allergic inflammation.
      METHODS: A fungal-associated allergenic proteinase (FAP) or ovalbumin was
      administered once intranasally to wild-type mice to determine their ability to
      induce allergy-associated genes and initiate allergic lung inflammation. Mice
      deficient in recombinase activating gene 1, C3a, the C3a anaphylatoxin receptor,
      and MyD88 were challenged similarly to understand the requirement of these
      molecules and T and B cells for allergic inflammation. Adoptive T-cell transfer
      experiments were further performed to determine whether signal transducer and
      activator of transcription 6 (STAT6) was required for cell recruitment and
      allergic inflammation. RESULTS: FAP, but not ovalbumin, induced eosinophilic
      airway inflammation and lung IL-4 production in the absence of adaptive immune
      cells after the transcriptional induction of allergy-specific airway chemokines.
      Allergen-mediated chemokine secretion and innate allergic lung inflammation
      occurred in the absence of STAT6, recombinase activating gene 1, C3a, C3a
      anaphylatoxin receptor, Toll-like receptor 4, and MyD88 but required intact
      proteinase activity. Furthermore, FAP induced recruitment of T(H)2 cells and
      eosinophils to lungs independently of STAT6, which was previously thought to be
      required for T(H)2 cell homing. CONCLUSION: FAP induces allergic lung
      inflammation through a previously unrecognized innate immune signaling mechanism.
      CLINICAL IMPLICATIONS: These findings reveal a new paradigm for understanding how
      allergic inflammation begins and suggest novel possibilities for the prevention
      and treatment of allergic diseases, such as asthma.

PMID- 17544099
TI  - Development of a simplified and standardized protocol with potential for high
      throughput for sperm cryopreservation in zebrafish Danio rerio.
AB  - Sperm cryopreservation offers potential for long-term storage of genetic
      resources. However, the current protocols for zebrafish Danio rerio are
      cumbersome and poorly reproducible. Our objective was to facilitate adoption of
      cryopreservation by streamlining methods from sperm collection through thawing
      and use. First, sperm activation was evaluated, and motility was completely
      inhibited when osmolality of the extender was >/=295-300mOsmol/kg. To evaluate
      cryoprotectant toxicity, sperm were incubated with dimethyl sulfoxide (DMSO), N,N
      dimethyl acetamide (DMA), methanol, or glycerol at 5, 10, and 15% concentrations.
      Based on motility, DMSO, DMA, and methanol (</=10%) were less toxic; therefore,
      sperm were cryopreserved using these cryoprotectants at cooling rates of 10 and
      20 degrees C/min. The highest motility (mean+/-S.D.) (35+/-23%; P</=0.0001) and
      fertility (13+/-8%; P</=0.001) in thawed sperm were obtained with the combination
      of 8% methanol and a cooling rate of 10 degrees C/min. Further evaluations of 8%
      methanol and 10 degrees C/min were performed with males from populations with
      high (2.05+/-0.24) and low (1.18+/-0.12) body condition (P=0.0001). Motility of
      thawed sperm from the two populations was 38+/-16% (range, 10 to 60%) and 78+/
      10% (50 to 90%) (P=0.0001), and fertilization was 6+/-6% (0 to 18%) and 33+/-20%
      (5 to 81%) (P=0.0001). These values were positively related with body condition
      factor. Overall, this study simplified and standardized sperm cryopreservation,
      and established a protocol using French straws as a freezing container and an
      extender without powdered milk. This protocol can be readily adapted for high
      throughput application using automated equipment, and motility and fertility
      comparable to previous reports were obtained. Male variability and sperm quality
      remain important considerations for future work, especially in mutant and inbred
      lines.

PMID- 17544100
TI  - Variability and repeatability in gestation length related to litter performance
      in female pigs on commercial farms.
AB  - Forecasting gestation length (GL) in sows enables producers to be prepared to
      provide assistance at farrowing, or for timely treatment to induce parturition.
      The objectives of the present study were to determine GL across parities, the
      repeatability and correlation of the GL, and associations of GL with the three
      litter size variables (total pigs born, pigs born alive, and dead piglets) and
      longevity. This study was conducted on 94 farms and encompassed 66,254 farrowing
      records of 13,715 sows born during 1999. Variance components and correlation
      analyses were used to determine the repeatability and the correlations of GL.
      Mixed-effects models were used to analyze associations of GL with litter size
      variables and longevity. The mean of GL across parities was from 115.2 to 115.4
      d. The proportions of GL 114, 115, and 116 d for all farrowing events were 19.2,
      30.8, and 22.2%, respectively. The GL between parities were correlated
      (0.40</=r</=0.56; P<0.01). The repeatability of GL was 0.50 on commercial farms.
      Shorter GL was associated with more numbers of total pigs born and dead piglets
      (P<0.01). Sows with GL 113 to 116 d had more pigs born alive than those with
      GL</=112 and >/=117 d (P<0.01). Sows with GL</=112 d were 1.57 and 2.21 times as
      likely to be culled as those with GL 115 d (P<0.01). It is recommended that swine
      producers maintain records of GL at each parity in individual sows.

PMID- 17544101
TI  - Luting of ceramic inlays in vitro: marginal quality of self-etch and etch-and
      rinse adhesives versus self-etch cements.
AB  - OBJECTIVES: To evaluate marginal integrity of IPS Empress inlays luted with
      different adhesives and cements before and after thermo-mechanical loading (TML).
      METHODS: MOD cavities with one proximal box beneath the cementoenamel junction
      were prepared in 72 extracted human third molars. IPS Empress inlays were luted
      with nine combinations of adhesive and luting composite or self-etch cement alone
      (n=8): Prime&Bond NT Dual-Cure+Calibra (PC), XP BOND/SCA+Calibra (XC), XP
      BOND/SCA light-cured+Calibra (XL), Syntac+Variolink II (SV), Multilink
      Primer+Multilink (ML), AdhesSE DC+Variolink II (AV), ED Primer+Panavia F 2.0
      (EP), RelyX Unicem (RU), and Maxcem (MC). Marginal quality was analyzed under an
      SEM using epoxy resin replicas before and after thermo-mechanical loading
      (100,000x50N and 2500 thermocylces between +5 and +55 degrees C). RESULTS: All
      systems involving the etch-and-rinse approach resulted in significantly higher
      percentages of gap-free margins in enamel than all other luting systems (p<0.05).
      ML and AV achieved higher percentages of gap-free margins in enamel than EP and
      RU (p<0.05), with EP and RU being significantly above MC (p<0.05). For dentine
      margins, XP Bond resulted in significantly higher percentages of gap-free margins
      than Prime&Bond NT, independent of a separate light-curing step (p<0.05). Between
      the luting systems XC, XL, SV, ML, AV, ED, EP, and RU, no significant differences
      were computed (p>0.05). MC ranged at the end of the statistical subsets with 62%
      gap-free margins (p<0.05; Mann-Whitney U-test). SIGNIFICANCES: Etch-and-rinse
      adhesives combined with conventional luting resin composites reveal still the
      best prognosis for adhesive luting of glass ceramic inlays.

PMID- 17544102
TI  - Morphological and compositional alterations of in vivo aged prefabricated
      pediatric metal crowns (PMCs).
AB  - OBJECTIVES: The purpose of the present study was to assess the morphological and
      elemental alterations of retrieved prefabricated metal crowns (PMCs) after
      intraoral exposure. METHODS: Seventeen in vivo aged stainless steel crowns (3M
      ESPE) were collected. The intraoral exposure time varied from 3 to 101 months.
      For every retrieved crown one new crown of the same type was used as a reference.
      The reference and in vivo aged crowns were examined by high-vacuum scanning
      electron microscopy and energy-dispersive X-ray microanalysis. The elemental
      composition between the as-received and in vivo aged crowns was statistically
      analyzed by t-test (a=0.05). RESULTS: In vivo aged crown surfaces demonstrated
      significantly morphological alterations with accumulation of amorphous intraoral
      integuments, biting imprints, wear and occlusal perforations. The results of
      microanalysis showed that there were no statistically significant differences in
      the elemental composition of the stainless steel crowns between the two
      conditions. SIGNIFICANCE: Under the conditions of the present study, retrieved
      prefabricated pediatric stainless steel crowns exhibit morphological changes
      mainly due to plastic deformation, without changes in elemental composition.

PMID- 17544103
TI  - Ammonium hexafluorosilicate elicits calcium phosphate precipitation and shows
      continuous dentin tubule occlusion.
AB  - Diamine silver fluoride [AgF: (NH(3))(2)AgF] has been used clinically in Japan,
      as it reduces dental caries and dentin hypersensitivity. However, AgF stains the
      teeth black due to silver precipitation. To overcome this drawback, the authors
      prepared ammonium hexafluorosilicate [SiF: (NH(4))(2)SiF(6)], which does not
      stain the teeth, and SiF occluded open dentin tubules completely with silica
      calcium phosphate precipitate. OBJECTIVES: The aim of this study was to evaluate
      the duration of dentin tubule occlusion after SiF treatment in a simulated oral
      environment. METHODS: To simulate dentin tubules subject to dentin
      hypersensitivity, dentin disks were treated with EDTA for 2 min. The disks were
      treated with 0.476 mol/L SiF for 3 min, and then the disks were immersed in
      synthetic saliva, which was regularly replenished to maintain its ionic
      concentration, for up to 7 days. The occluding ability of the dentin tubules was
      evaluated using scanning electron microscopy (SEM), and the hydraulic conductance
      was measured following Pashley's method at regular intervals. RESULTS: SEM
      photographs demonstrated that dentin tubules were occluded homogeneously and
      completely with the precipitate at 7 days after treatment with SiF. In addition,
      newly formed calcium phosphate precipitate was present at the dentin surface. The
      dentin permeability showed a consistently low value throughout the experimental
      period. The values immediately after SiF treatment and 7 days after immersion
      were 11.9+/-3.7% and 7.9+/-2.9%, respectively. SIGNIFICANCE: Ammonium
      hexafluorosilicate is useful for the treatment of dentin hypersensitivity, since
      ammonium hexafluorosilicate induced calcium phosphate precipitation from the
      saliva; therefore, it has a continuous effect on dentin tubules occlusion under a
      simulated oral environment.

PMID- 17544105
TI  - The patient with GORD and chronically recurrent problems.
AB  - Treatment of gastro-oesophageal reflux disease (GORD) by means of gastric acid
      secretion inhibition usually is successful. When symptoms persist despite
      adequate treatment, correctness of the diagnosis of GORD should be questioned.
      Quite often dyspeptic symptoms are erroneously interpreted as GORD symptoms.
      Other causes of treatment failure are insufficient acid suppression and
      oesophageal hypersensitivity. In the management of patients with persistent
      symptoms oesophageal pH and impedance monitoring are useful techniques. These may
      provide answers to the question whether the symptoms are reflux-related and
      whether acid secretion is adequately suppressed.

PMID- 17544106
TI  - The difficult patient with gastroparesis.
AB  - Gastroparesis is often difficult to manage. First of all, exact criteria for
      making a diagnosis of gastroparesis have not been established, and merely finding
      delayed gastric emptying does not justify the label. Furthermore, the
      relationship between symptoms and gastric emptying rate is poor, and the number
      of therapies with proven efficacy is extremely limited. A number of technical
      investigations are helpful to establish the anatomy and motor function of the
      upper gastrointestinal tract. In most cases where gastroparesis can be presumed
      or established, prokinetic therapy will be tried. A number of agents are
      available, with variable efficacy and tolerance. Rarely, in case of debilitating
      refractory symptoms, experimental or invasive therapies can be tried such as
      injection of botulinum toxin, enteral feeding tube insertion, gastric electrical
      stimulation or surgery.

PMID- 17544107
TI  - The patient with recidivent obscure gastrointestinal bleeding.
AB  - Obscure gastrointestinal (GI) bleeding is defined as visible or invisible GI
      blood loss, the source of which can not be identified by standard endoscopy
      (oesophagogastroduodenoscopy and colonoscopy). Nowadays, GI bleeding is divided
      into upper, mid- and lower bleeding. Mid-GI bleeding covers the section from the
      Treitz ligament to the ileocaecal valve. The new diagnostic methods of capsule
      endoscopy and double balloon enteroscopy have revolutionised the diagnostic
      approach in recent years. As a result, previous radiological and nuclear medicine
      techniques (small bowel X-ray, scintigraphy and angiography), but also endoscopic
      techniques, such as the push enteroscopy and intraoperative endoscopy, are
      becoming less important. After standard endoscopy and persistent blood loss it is
      advisable to first have these procedures repeated by an experienced examiner
      under optimal conditions. Nevertheless, no source of bleeding is identified by
      this method in 5% of cases. It is then recommended to use capsule endoscopy and,
      depending on the findings, double balloon enteroscopy with the option of
      intervention. In patients with unstable circulation an invasive procedure
      (intraoperative endoscopy) may be required.

PMID- 17544108
TI  - The patient with multiple intestinal polyps.
AB  - The management of patients with multiple intestinal polyps may be difficult and
      greatly depends on the correct classification. Polyposis syndromes account for
      less than 1% of newly diagnosed colorectal cancers. In addition the risk for
      extracolonic cancer is increased in most syndromes. Here we report the case of a
      difficult patient with severe gastric polyposis and we present a review of
      polyposis syndromes such as classical and attenuated familial adenomatous
      polyposis (FAP), MYH-associated polyposis, Peutz-Jeghers syndrome, juvenile
      polyposis as well as rare polyposis syndromes. The most practical approach for
      the diagnostic workup in patients with newly diagnosed gastrointestinal polyposis
      is based on the histological typing of polyps. In addition, a detailed family
      history regarding cancer, polyps and congenital abnormalities should be obtained
      from every polyposis patient. Patients with multiple adenomas are most likely to
      suffer from FAP, AFAP or MAP. Of these, younger age and higher polyp count are
      most likely a diagnosis of typical FAP. Older age and fewer polyps favour a
      diagnosis of AFAP or MAP. Germline testing of the APC gene is suggested, and if
      negative, MYH gene testing should be done. In patients with hamartomas,
      extraintestinal features should be evaluated and reference histology should be
      initiated. In addition panintestinal imaging should be performed with EGD,
      colonoscopy and small bowel imaging (PE, CE, and MR) enteroclysis. For diagnostic
      and therapeutic problems a familial colorectal cancer center should be consulted.
      Using this algorithm, correct classification and adequate treatment should be
      possible for every polyposis patient.

PMID- 17544109
TI  - The patient with recurrent (sub) obstruction due to Crohn's disease.
AB  - Stricturing Crohn's disease (CD) occurs in 12-54% of the CD patient population
      and is associated with significant morbidity and impaired quality of life. The
      detailed pathophysiology of stricture formation has not been fully elucidated,
      but is primarily associated with luminal narrowing secondary to inflammation and
      the fibrosis that ensues during mucosal healing. The diagnosis of stricturing
      disease is based on clinical signs and symptoms along with imaging modalities.
      The advantages and shortcomings of each imaging modality are discussed. Treatment
      options are based on the differentiation between inflammatory versus fibrous
      predominant strictures; whereas the former can potentially be managed with
      conservative medical treatment, the latter necessitates a mechanical solution
      through endoscopy or surgery. Indications, contra-indications and success rates
      of the different therapeutic approaches are discussed.

PMID- 17544110
TI  - The difficult patient in gastroenterology: chronic pelvic pain, adhesions, and
      sub occlusive episodes.
AB  - Chronic pelvic pain (CPP) with or without adhesions and symptoms of intestinal
      occlusion is a complex but relatively common complaint. The etiology and
      pathophysiology of CPP and adhesions are unclear, as is their possible relation.
      However, it is evident that continuous abdominal pain leads to evident suffering
      and disability. Unfortunately, there is little proof or evidence of success for
      many of the currently used diagnostic and therapeutic interventions. Laparoscopy
      is neither the ultimate evaluation nor the panacea for CPP or intra abdominal
      adhesions. An integral approach to CPP has shown beneficial results. In this
      multidisciplinary approach dealing with the pain is far more important than
      finding an organic cause and cure for the pain. Equal and simultaneous attention
      is paid to psychosocial, sexual and somatic aspects. The treatment of adhesions
      depends on the extent of symptoms and complaints. Because of the questionable
      relation between adhesions and pain, and the probability of reformation and de
      novo adhesion formation after surgery, adhesiolysis should be avoided. Even for
      patients with signs and symptoms of small bowel obstruction a conservative
      treatment is often justified. These patients require careful evaluation and
      management. Frequent reassessment is important to rule out impending
      strangulation, complete obstruction or perforation. Water soluble contrast can be
      useful to justify prolongation of conservative treatment and by that postpone
      unnecessary surgery. Most adhesive small bowel obstructions resolve following
      conservative treatment. The unsolved questions about etiology, diagnosis,
      treatment and prevention, and the great individual and community burden of CPP
      and adhesions clearly show that further research is needed.

PMID- 17544111
TI  - Severe chronic abdominal pain in the absence of adhesions.
AB  - Management of the patient with chronic severe abdominal pain in the absence of
      adhesions remains one of the major challenges of the gastroenterologist. Given
      that extensive investigation will inevitably take place of such individual, the
      role of the gastroenterologist who is asked to review such a problem, is to
      identify unusual manifestations of common disorders from new, previously
      unidentified causes, and to assess the degree to which somatisation and
      psychological overlay are exacerbating the problem. Investigations must be
      targeted against clinically-generated hypotheses rather than to repeat a non
      systematic approach. Therapy in the absence of a newly-identified disorder is
      generally targeted at alleviating rather than removing symptoms, addressing an
      individual's personal pain and management needs, and avoiding ever more complex
      and invasive investigations.

PMID- 17544112
TI  - The difficult patient with constipation.
AB  - Difficult patients with constipation mostly suffer for years, have consulted more
      than one physician and have had some experience with laxatives. The first step
      should be sorting out what exactly the patient's problem is. For this purpose
      technical investigations may be helpful, but the most important measures are a
      detailed history, symptom analysis and proctological examination. Rarely, an
      underlying and treatable cause of the constipation can be identified. In
      disordered defaecation this may be a large rectocele or an intussusception of the
      rectum amenable to proctosurgery. In most cases, however, some form of laxative
      treatment will be required. For this purpose, a detailed knowledge of their
      pharmacology is mandatory. The type of laxative and the schedule of
      administration often have to be determined on an individual basis over a number
      of weeks. In some patients, combination treatment with macrogol and a stimulant
      laxative may be the solution. Psychological features must also be taken into
      account in difficult patients, in particular if they ask for colectomy. Total
      colectomy with ileorectal anastomosis is an effective (although not universally
      successful) treatment of constipation, which is, however, hampered by a high rate
      of both early and late complications.

PMID- 17544113
TI  - The patient with refractory diarrhoea.
AB  - Persistent diarrhoea continues to present a management challenge to clinicians
      around the world. The investigation of persistent diarrhoea requires a logical
      hierarchical approach to ensure that resources are used appropriately and
      patients are not put at unnecessary risks during the investigative process. A 5
      step process is described in which functional diarrhoea is excluded early in the
      workup, which might include a measurement of 24h faecal weight. Once infection,
      drugs and laxatives have been excluded more invasive tests such as endoscopy are
      sequentially introduced to exclude inflammatory disease and small bowel and
      pancreatic malabsorption. When the common causes have been excluded there remains
      a group of patients with high volume watery diarrhoea due to a variety of causes
      include the neuroendocrine diarrhoeas. A case of fictitious diarrhoea is
      described which illustrates the value of complete fluid balance studies, faecal
      osmolality and other biochemical faecal analyses. The management of some selected
      causes of refractory diarrhoea is discussed including functional diarrhoea,
      diabetic diarrhoea, diarrhoea dues to protozoal infections, microscopic colitis
      and antibiotic associated diarrhoea.

PMID- 17544114
TI  - The patient with persistent perianal fistulae.
AB  - The management of patients with persistent perianal fistulae depends on thorough
      evaluation by clinical history and examination, assessment of intestinal disease
      and assessment of perianal disease. The main therapeutic options are medical and
      surgical treatment and their appropriate integration is essential for the optimal
      management of the patients. Medical treatment includes antibiotics, azathioprine
      or 6-mercaptopurine, infliximab and tacrolimus or cyclosporine. Surgical
      treatment includes fistulotomy, placement of setons, endorectal advancement
      flaps, fecal diversion and proctectomy. Fistula recurrence often occurs, possibly
      due to early discontinuation of medication or premature removal of setons. Using
      anorectal endoscopic ultrasound or magnetic resonance imaging to guide therapy,
      the healing rates of perianal fistula can be increased. In persistent complex
      perianal fistulae where medical treatment initially fails, examination under
      anaesthesia and placement of non-cutting setons, when necessary, combined with
      medical treatment results in higher healing rates.

PMID- 17544115
TI  - The patient with slightly elevated pancreatic enzymes and abdominal complaints.
AB  - Abdominal complaints in combination with slightly elevated serum pancreatic
      enzymes represent a classical clinical challenge. These symptoms may be due to
      coincidental unrelated harmless disorders, benign pancreatic alterations which
      are fairly easily treatable such as mild acute pancreatitis or uncomplicated
      chronic pancreatitis. However, serious, often insidious diseases such as
      pancreatic tumours may also present with this constellation as their first signs.
      Diagnostic procedures need to be stratified according to acuteness and severity
      of symptoms. While patients with acute onset of symptoms and severe complaints
      need immediate and combined laboratory and imaging investigations to allow
      adequate therapy, chronic and mild complaints usually justify a stepwise
      diagnostic approach consecutively using abdominal ultrasound, CT/MRI and
      endoscopic ultrasound as imaging procedures and reserving ERCP for cases which
      remain unclear or in which interventional therapy is needed. Diagnosis and follow
      up are often particularly demanding in patients with cystic tumours of the
      pancreas. In chronic pancreatitis patients pain therapy and adequate control of
      pancreatic exocrine insufficiency may pose major problems. Patients with
      refractory pain may ultimately require surgical intervention. Another important
      indication for surgery in chronic pancreatitis is suspicion of cancer that cannot
      be ruled out by dedicated diagnostic procedures. This also applies to cystic
      tumours of the pancreas, which have a high risk of malignant transformation or
      may even already represent pancreatic cancer at the time of diagnosis.

PMID- 17544116
TI  - The patient with unexplained elevated serum liver enzymes.
AB  - The pattern of elevated serum liver enzymes in symptomatic or asymptomatic
      patients allows for an initial classification of liver diseases into cholestatic
      or hepatocellular diseases. A female patient with extrahepatic cholestasis due to
      segmental bile duct strictures and a localized mass lesion within the pancreas is
      presented. Although many diagnostic procedures were performed in this case the
      diagnosis was not obtained before surgical laparotomy was initiated with bioptic
      sampling from bile ducts, lymph nodes and pancreatic tissue. Microscopic
      examination of the specimen revealed extensive biliary and pancreatic scarring
      together with periductal infiltrates composed of lymphocytes and plasma cells
      consistent with sclerosing cholangitis in systemic autoimmune pancreatitis. The
      patient completely recovered upon treatment with prednisone and azathioprine. The
      difficult approach to the final diagnosis is discussed in light of established
      and modern diagnostic tools.

PMID- 17544117
TI  - The patient with refractory ascites.
AB  - Refractory ascites indicates advanced chronic liver disease and represents a
      therapeutic challenge. It may be triggered by spontaneous bacterial peritonitis
      and denotes poor prognosis. While liver transplantation is the ultimate
      treatment, for the relief of ascites therapeutic paracentesis with iv
      administration of albumin and/or transjugular intrahepatic portosystemic shunt
      (TIPS) are well established. With rapid deterioration of renal function patients
      can develop hepatorenal syndrome. There is increasing evidence that these
      patients can be bridged to transplantation with vasopressin analogs
      (terlipressin) and albumin.

PMID- 17544118
TI  - Magnetic control of vascular network formation with magnetically labeled
      endothelial progenitor cells.
AB  - We describe the applications of new cellular magnetic labeling method to
      endothelial progenitor cells (EPC), which have therapeutic potential for
      revascularization. Via their negative surface charges, anionic magnetic
      nanoparticles adsorb non-specifically to the EPC plasma membrane, thereby
      triggering efficient spontaneous endocytosis. The label is non-toxic and does not
      affect the cells' proliferative capacity. The expression of major membrane
      proteins involved in neovascularisation is preserved. Labeled cells continue to
      differentiate in vitro and to form tubular structures in Matrigel (an in vitro
      model of neovascularization). This process was followed in situ by using high
      resolution MRI. Finally, we show that magnetic forces can be used to move
      magnetically labeled EPC in vitro and to modify their organization in Matrigel
      both in vitro an in vivo. Magnetic cell targeting opens up new possibilities for
      vascular tissue engineering and for delivering localized cell-based therapies.

PMID- 17544119
TI  - Multiple signal pathways in the leukemogenesis and therapeutic implications.

PMID- 17544120
TI  - Clinical spectrum of gammadelta+ T cell LGL leukemia: analysis of 20 cases.
AB  - We report on the clinico-biological characteristics of 20 cases of gammadelta T
      cell large granular lymphocyte (LGL) leukemia. All the data were compared to that
      of 196 cases with alphabeta T cell subtype, which represents the majority of T
      cell LGL leukemias. Clinical findings were quite similar in the two groups
      regarding age, sex ratio, recurrent infections, and association with auto-immune
      diseases especially rheumatoid arthritis. Gammadelta LGL predominantly expressed
      a CD3+/CD4-/CD8+/CD16+/CD57+ phenotype, in 50% of cases. Clinical outcome was
      favorable for these patients with overall survival of 85% at 3 years. Fifty
      percent of gammadelta patients required treatment and the response to therapy was
      estimated at 55%. gammadelta and alphabeta T cell LGL leukemia harbor a very
      similar clinico-biological behavior and represent part of an antigen-driven T
      cell lymphoproliferation.

PMID- 17544121
TI  - Flow cytometric quantification of proliferating coelomocytes non-invasively
      retrieved from the earthworm, Dendrobaena veneta.
AB  - Earthworms irritated naturally (e.g. by predators) or experimentally extrude
      coelomocyte-containing coelomic fluid through the dorsal pores of the body wall.
      In the present study, the earthworms, Dendrobaena veneta, experimentally depleted
      of free-floating coelomocytes by multiple electric shocks (1 min, 4.5 V) remained
      fully vital and coelomocyte depletion was followed by the extensive cell
      replenishment, which was more efficient in the case of amoebocytes than
      autofluorescent eleocytes/chloragocytes, quantified by flow cytometry.
      Immunohistochemical procedure with antibodies against human Ki-67 proliferation
      antigens revealed proliferating cells on cytospin preparations of coelomocytes
      extruded by electric shock. Quantification of proliferating cells in the
      suspension of extruded coelomocytes was performed by flow cytometry on FL-2
      profiles of propidium iodide-stained samples; riboflavin-derived autofluorescence
      of eleocytes/chloragocytes was lost during detergent treatment. As expected, the
      percentage of coelomocytes proliferating in coelomic fluid was increased during
      restoration of coelomocyte number after experimental depletion. The method
      described here may be very useful for investigations of antigen-driven
      proliferation of earthworm coelomocytes.

PMID- 17544122
TI  - The evolution of the role of the registered nurse in the management of analgesia
      by catheter techniques.

PMID- 17544123
TI  - Registered nurse management and monitoring of analgesia by catheter techniques:
      position statement.
AB  - The American Society for Pain Management Nursing believes that the administration
      of analgesia and the management of the associated effects are fundamental nursing
      responsibilities. This position statement will address the registered nurse's
      responsibilities for the management and monitoring of analgesia by catheter
      techniques in all patients of all ages and in all care settings. It will provide
      recommendations for the health care institution, licensed independent
      practitioner, and registered nurse to ensure the safe and effective
      implementation of these pain control methods. The position statement reinforces
      the American Society for Pain Management Nursing's belief that the administration
      of analgesia by catheter techniques is within the registered nurse scope of
      practice.

PMID- 17544124
TI  - Perceptions of control over pain by patients with cancer and their caregivers.
AB  - The purpose of this qualitative inquiry was to broaden the context for
      understanding perceived control as a concept related to the cancer pain response
      in the homecare setting. Ten patient/caregiver dyads participated in
      semistructured interviews focused on questions pertaining to the patients'
      perceived control over their own pain as well as the caregivers' control over the
      patients' pain. Line-by-line analysis was used to code, categorize, and analyze
      the data. Six themes emerged among patients: feeling robbed of the simplest of
      tasks and pleasures, the pain is hungry, feeling desperate, the pain is winning,
      fatigue/sleep disturbances, and perceived control is soothing. For the
      caregivers, four main themes emerged: monitoring the suffering, feeling like an
      outsider, inability to control the interventions, and importance of resources.
      Overall, patients and their caregivers were eager to discuss how their perceived
      lack of control over pain affected their daily lives. The results suggest
      perceived control over pain is an important aspect of the pain response in the
      homecare setting. Nurses should evaluate perceived control over pain in patients
      with cancer and their caregivers and implement and test potential methods for
      increasing perception of control over pain.

PMID- 17544125
TI  - Multicultural influences on pain medication attitudes and beliefs in patients
      with nonmalignant chronic pain syndromes.
AB  - The objective was to develop an integrated review of quantitative and qualitative
      research regarding the influence of patients' beliefs and attitudes toward pain
      medication prescribed for the treatment of nonmalignant chronic pain on use of
      the pain medication. Studies involving patients at least 18 years old with
      nonmalignant chronic pain were included. Studies of patients with acquired immune
      deficiency syndrome, cancer, and acute pain were excluded. Medline, CINAHL,
      PsychInfo, and Cochrane databases from 1985 to 2005 were searched. Reference
      lists were screened for relevant articles. Abstracts were screened for compliance
      with the study criteria, and the articles were obtained for those that met
      criteria. By using a systematic process, each article was subjected to repeated
      review and data abstracted to the collection sheets. Evidence tables were created
      to assist with data review. High levels of concern positively correlate with
      nonadherence, preconceived ideas about when the drug should start working can
      cause the patient to discontinue it before it begins to work, and patients may
      perceive that if medication is taken on a regular basis to control pain it may
      not be effective in the future if the pain increases. Research also showed that
      if patients perceived the benefits of taking the pain medication to be high, they
      were willing to risk the side effects.

PMID- 17544126
TI  - Accuracy of parental-global-impression of children's acute pain.
AB  - The primary purpose of this study is to compare parental-global-impression of
      children's level of acute pain at home with parental assessment of children's
      pain using a structured instrument and with children's self-reports of pain. We
      recruited 32 parents of children aged 5 to 10 years who were diagnosed with a
      fractured limb and treated in a tertiary emergency department. After discharge,
      parents were asked to complete three home-based assessments relating to their
      child's acute pain: the parental-global-impression of pain, child's reported
      pain, and structured Parental Postoperative Pain Measure. Data analysis included
      odds ratios, sensitivity, specificity, positive and negative predictive values,
      and repeated-measures analysis of variance. When compared with child report of
      pain, the sensitivity of parental-global-impression was 76% on day 1 and 93% on
      day 2, whereas specificity was 91% on day 1 and 83% on day 2. When compared with
      child report of pain, the sensitivity of Parental Postoperative Pain Measure was
      71% on day 1 and 66% on day 2, whereas specificity was 82% on day 1 and 83% on
      day 2. On the basis of acceptable statistical criteria, parental-global
      impression has good sensitivity and specificity compared with the child self
      report measure. We do not suggest, however, that parental-global-impression can
      or should replace child report, but rather suggest that it can be used as an
      adjunct assessment measure as needed.

PMID- 17544127
TI  - Assessing pain in persons with dementia: relationships among the non
      communicative patient's pain assessment instrument, self-report, and behavioral
      observations.
AB  - Pain is a common problem for many older adults, with up to 50% of community
      dwelling and 70% to 80% of nursing home residents experiencing pain regularly.
      Effective pain management requires thorough assessment, appropriate intervention,
      and systematic reassessment. Pain assessment, however, is complicated by
      dementia, which impairs memory, reasoning, recognition, and communication, and
      affects elders' ability to verbally report pain. As such, observational measures
      are needed to assess pain in this vulnerable population. The Non-communicative
      Patient's Pain Assessment Instrument (NOPPAIN) was developed for this purpose,
      but more validation of this measure is needed. Thus, the purpose of this study
      was to (1) evaluate reliability of the NOPPAIN tool when used by nurses and to
      (2) compare NOPPAIN ratings with self-report and other well-established
      behavioral rating procedures. Forty participants (20 cognitively intact and 20
      impaired) were randomly selected for this study from a larger sample. In the
      parent study, participants were asked to perform everyday activities (i.e., sit,
      stand, walk in place, transfer in and out of bed) while being videotaped. The
      tapes, all previously scored using microanalytic observational coding, were rated
      again by naive raters using the NOPPAIN measure. Results indicated (1) high inter
      and intrarater reliability of the NOPPAIN and (2) significant correlations of
      the NOPPAIN with self-reported pain and detailed behavioral coding. Findings
      support the reliability and validity of the NOPPAIN measurement tool and suggest
      this easy-to-use tool may be adequate for measuring pain indicators in older
      adults.

PMID- 17544128
TI  - Improving patient and nurse outcomes: a comparison of nurse tasks and time
      associated with two patient-controlled analgesia modalities using delphi panels.
AB  - Increased demand on nursing time may adversely affect nurse satisfaction and
      patient outcomes. Technologies to reduce nursing time and burden may improve
      patient care. Two Delphi panels assessed the perceived nursing time of fentanyl
      iontophoretic transdermal system (ITS) and intravenous patient-controlled
      analgesia (IV PCA) for postoperative pain management. The panels were asked to
      estimate the time spent on individual nursing tasks from a list. The Clinical
      Trial panel (n = 14) was composed of nurses who participated in two clinical
      trials, and data for both PCA modalities were collected from this panel. The
      routine practice panel (n = 13) was composed of nurses from various hospital
      units, and only data for IV PCA were collected from this panel. From the Clinical
      Trial panel, the estimated total average task time was 251 minutes for IV PCA and
      210 minutes for fentanyl ITS. From the Routine Practice panel, the estimated
      total average task time was 163 minutes for IV PCA. Thirteen extra tasks were
      identified by the Clinical Trial panel to be associated only with IV PCA, and
      these eliminated steps primarily explained the estimated total nursing time
      difference between IV PCA and fentanyl ITS. According to the two Delphi panels,
      the perceived nursing time consumed was less and the number of tasks was lower
      for fentanyl ITS than for IV PCA. This benefit associated with fentanyl ITS may
      lead to other positive outcomes, such as improved nurse satisfaction and improved
      patient outcomes.

PMID- 17544129
TI  - Improving goal setting and goal attainment in patients with chronic noncancer
      pain.
AB  - Chronic noncancer pain (CNCP) is a major problem in health care today. Management
      of patients who have CNCP often poses a challenge for health care providers
      because their goals are nonspecific and as a group they are prone to frustration
      and depression. This article evaluates the characteristics of therapeutic goal
      setting, barriers to goal setting, and potential solutions to this problem. If
      the patients with CNCP can be assisted to set realistic goals, both patient care
      and its outcomes will improve.

PMID- 17544130
TI  - Accepting pain management or seeking pain cure: an exploration of patients'
      attitudes to chronic pain.
AB  - This article explores the differing attitudes of patients toward chronic pain.
      Because pain is a subjective experience, individuals react to living with chronic
      pain in varying ways. Some patients successfully manage their chronic pain,
      whereas others continue to seek a pain cure. A convenience sample (n = 8) was
      generated from a district general hospital's nurse-led pain clinic. The sample
      was subdivided by an expert panel rating procedure into two groups: those
      accepting pain management and those seeking a pain cure. The study used a
      multimethod approach comprising extended, highly focused interviews coupled with
      patients' diaries and drawing on a phenomenologic theoretical framework. Initial
      hermeneutic data analysis provided emerging themes: "rules for living," "pain =
      life," and "acceptance" for the pain management group, and "pillar to post,"
      "self-fulfilling prophecy," and "mood" for those seeking a cure. Thematic content
      common to both groups were "family" and "coping strategies." These themes
      illustrate some differences and similarities between those who manage pain
      compared with those who seek a pain cure. Phenomenologically based research
      findings can rarely be generalized, but they enlighten and highlight the need for
      further research to generate detailed understanding of why some patients with
      chronic pain can accept pain management and others relentlessly seek a cure that
      is frequently not possible.

PMID- 17544131
TI  - Molecular connexions between dementia and diabetes.
AB  - Recent evidence suggests that the molecular defects associated with the
      development of diabetes also contribute to an increased risk of all types of
      dementia, including Alzheimer's disease, vascular dementia and Pick's disease.
      Indeed, the presence of type II diabetes mellitus results in a two to three fold
      higher risk of developing dementia [Fontbonne et al., 2001. Changes in cognitive
      abilities over a 4-year period are unfavourably affected in elderly diabetic
      subjects: results of the Epidemiology of Vascular Aging Study. Diabetes Care 24,
      366-370; Gregg et al., 2000. Is diabetes associated with cognitive impairment and
      cognitive decline among older women? Study of Osteoporotic Fractures Research
      Group. Archives of Internal Medicine 160, 174-180; Peila et al., 2002. Type 2
      diabetes, APOE gene, and the risk for dementia and related pathologies: The
      Honolulu-Asia Aging Study. Diabetes 51, 1256-1262]. There are currently 250
      million people worldwide (>2 million in the UK) diagnosed with diabetes, and this
      number is predicted to double within the next 20 years, therefore the associated
      risk translates into a potential explosion in the appearance of dementia in the
      population. This review primarily focuses on the proposed molecular links between
      insulin action, Diabetes and Alzheimer's disease, while discussing the potential
      for therapeutic intervention to alleviate these disorders. In particular, we will
      review the regulation of glycogen synthase kinase-3 (GSK-3) and its neuronal
      substrates.

PMID- 17544132
TI  - The meaning of the message.

PMID- 17544133
TI  - War or cancer.

PMID- 17544134
TI  - Another way to think about insurance: government action distorts the market price
      with harmful side effects.

PMID- 17544135
TI  - Risky business.

PMID- 17544136
TI  - Legitimate lease arrangement or suspect joint venture?

PMID- 17544137
TI  - Establishing a cardiac imaging service.
AB  - The tremendous progress in the field of cardiac imaging has drawn the interest of
      many radiologists, but has left them uncertain as to how obtain the training
      necessary to become expert practitioners. This review addresses the challenges in
      establishing a cardiac imaging service including equipment issues, training and
      credentialing issues, as well as referrals and reimbursement.

PMID- 17544138
TI  - Debt, demographics, and dual degrees: American medicine at the crossroads: part
      1: marketplace issues.
AB  - After a quarter century of national policy guided by two principal themes-fear of
      a physician workforce glut and official preference for careers in primary care
      medicine-the Council on Graduate Medical Education in January 2005 reversed
      course and announced its projection of a general physician shortage by 2020 and
      specifically named several specialties, including radiology, in which the
      shortage would be most severe. In response, the Association of American Medical
      Colleges initially proposed that medical schools increase enrollment by 15% and
      subsequently by 30% over the next 10 years. In the first of 3 articles devoted to
      the physician workforce crisis, the market model is applied to medical services,
      and questions are raised about the feasibility of the proposed medical school
      expansion.

PMID- 17544139
TI  - Digital radiography image quality: image acquisition.
AB  - This article on digital radiography image acquisition is the first of two
      articles written as part of an intersociety effort to establish image quality
      standards for digital and computed radiography. The topic of the other paper is
      digital radiography image processing and display. The articles were developed
      collaboratively by the ACR, the American Association of Physicists in Medicine,
      and the Society for Imaging Informatics in Medicine. Increasingly, medical
      imaging and patient information are being managed using digital data during
      acquisition, transmission, storage, display, interpretation, and consultation.
      Data management during each of these operations has a direct impact on the
      quality of patient care. These articles describe what is known to improve image
      quality for digital and computed radiography and make recommendations on optimal
      acquisition, processing, and display. The practice of digital radiography is a
      rapidly evolving technology that will require the timely revision of any
      guidelines and standards. This document provides a basis for the technologies
      available today in clinical practice and may be useful in guiding the future
      clinical practice of digital radiography.

PMID- 17544140
TI  - Digital radiography image quality: image processing and display.
AB  - This article on digital radiography image processing and display is the second of
      two articles written as part of an intersociety effort to establish image quality
      standards for digital and computed radiography. The topic of the other paper is
      digital radiography image acquisition. The articles were developed
      collaboratively by the ACR, the American Association of Physicists in Medicine,
      and the Society for Imaging Informatics in Medicine. Increasingly, medical
      imaging and patient information are being managed using digital data during
      acquisition, transmission, storage, display, interpretation, and consultation.
      The management of data during each of these operations may have an impact on the
      quality of patient care. These articles describe what is known to improve image
      quality for digital and computed radiography and to make recommendations on
      optimal acquisition, processing, and display. The practice of digital radiography
      is a rapidly evolving technology that will require timely revision of any
      guidelines and standards.

PMID- 17544141
TI  - Exclusive contracts in the hospital setting: a two-edged sword: part 2: pros and
      cons, avoidance strategies, and negotiating tips.
AB  - Hospitals routinely enter into contracts with radiology groups for the right to
      be the exclusive providers of radiologic services at the facilities in exchange
      for the groups' agreeing to provide and manage all aspects of those services
      within the hospitals. These exclusive contracts generally result in radiology
      departments and associated equipment being closed off to physicians who are not
      part of the contracting groups. Although exclusive contracts offer obvious
      benefits to the physicians who receive them and obvious disadvantages for those
      who are excluded, they also present pitfalls for physicians in the chosen group.
      Part 1 of this article discussed the legal issues raised by exclusive contracts.
      Part 2 weighs the practical advantages and disadvantages of exclusive contracts
      for physicians covered and not covered by such contracts and strategies for
      avoiding them, as well as provisions that can be included in medical staff bylaws
      to protect physicians from the automatic termination of privileges when a
      hospital enters into or terminates an exclusive contract. The remainder of the
      article provides tips on specific provisions of exclusive contracts that should
      be included or avoided.

PMID- 17544142
TI  - Reassignment reform: a possible regulatory tool to stunt the growth of in-office
      imaging.
AB  - The expansion of the Medicare reassignment rule in 2003 to permit independent
      contractors to perform professional services off-site has been cited as a factor
      potentially contributing to the marked increase in physician practices billing
      for diagnostic testing. In an effort to curb this growth, the Centers for
      Medicare and Medicaid Services is contemplating further revisions to the Medicare
      reassignment rules as described below that would effectively preclude ordering
      physicians from marking up not only the technical, but also the professional
      components of any services purchased or obtained under contract from radiology
      groups or other imaging service providers.

PMID- 17544143
TI  - Pay for performance: survey of diagnostic radiology faculty and trainees.
AB  - PURPOSE: Pay-for-performance (P4P) programs have been implemented in many health
      care markets in the United States. The purpose of this study was to survey
      faculty members and trainees regarding familiarity with the P4P model and their
      interest in further education. METHODS: An eight-question survey designed to
      explore faculty member and trainee awareness of and attitudes toward P4P was
      distributed. Data were analyzed using Microsoft Excel. RESULTS: One hundred four
      of 144 questionnaires distributed to faculty members (50 of 70) and trainees (54
      of 74) were returned. Sixty-one percent of trainees stated that they had never
      heard of the P4P model. Seventeen percent of trainees and 26% of attending
      radiologists were aware that P4P programs have already been instituted. Although
      74% of trainees agreed that P4P will influence their reimbursement in the future,
      only 42% of attending radiologists agreed. A minority of trainees and attending
      radiologists (35%) felt that P4P improves the quality of care, whereas 42% were
      neutral. A majority were interested in further education. CONCLUSION: Faculty
      members and trainees in diagnostic radiology in a university-based program were
      unfamiliar with the P4P model of reimbursement and were interested in learning
      more. Additional investigation is needed to ascertain whether this knowledge gap
      is widespread. This could influence future education about P4P on a national
      level.

PMID- 17544144
TI  - Implementing a replacement PACS: issues to consider.

PMID- 17544145
TI  - Intensity-modulated arc therapy: new developments on an old idea.

PMID- 17544146
TI  - Evaluating pulmonary nodules.

PMID- 17544147
TI  - Henry J. Walton.

PMID- 17544148
TI  - CT screening for lung cancer: editorials can be deceiving.

PMID- 17544150
TI  - Anti-allergic properties of a new all-D synthetic immunoglobulin-binding peptide.
AB  - Using a combinatorial chemistry approach, we identified a tetrameric tripeptide,
      denoted Protein A Mimetic (PAM) or TG19318, able to bind to immunoglobulins of
      different classes and species. The inverso variant, with the tripeptide in the
      all-D configuration (D-PAM or TG19320), is described as retaining binding
      properties to Ig. This peptide has now been assayed as a binder for E class
      immunoglobulins, in linear and competitive ELISA experiments, dot-blot and
      surface plasmon resonance (SPR) analyses. We show that D-PAM binds IgE with high
      specificity and selectivity, the interaction being sufficient to inhibit
      anaphylactic release of beta-hexosaminidase from RBL 2H3 cells, with an IC50
      value of 10 microg/mL. Intradermal administration of D-PAM suppresses PCA in the
      rat, with an IC50 of 1.25 microg/kg dose of peptide, while its intraperitoneal
      injection inhibits mouse PCA with an IC50 of about 7 mg/kg and an efficacy
      comparable to that of ketotifen. Similarly, D-PAM inhibits ACA in the mouse, with
      50% suppression at 10 mg/kg. The results presented here show that the peptide is
      active on the studied models, with effective doses below toxicity level, hence
      the molecule is a promising candidate for development of a new class of anti
      allergic drugs.

PMID- 17544151
TI  - Synthesis, spectroscopic and X-ray characterization of a copper(II) complex with
      the Schiff base derived from pyridoxal and aminoguanidine: NMR spectral studies
      of the ligand.
AB  - A copper(II) complex with the pyridoxal-aminoguanidine (PL-AG) Schiff base
      adduct, as an organic compound of the very potent biological activity and
      promising pharmacological importance in the treatment of diabetic complications,
      has been prepared and characterized. The X-ray structural analysis of the
      [CuCl2(PL-AG)] complex showed that it has a distorted pseudo-square-pyramidal
      (4+1) structure with the tridentate ONN Schiff base in the equatorial plane, with
      the Cu-O(1), Cu-N(1) and Cu-N(3) bond lengths of 1.917(2)A, 1.930(2)A and
      1.984(2)A, respectively. The bond length of the equatorial Cu-Cl(1) is 2.279(1)A,
      while that of the apical Cu-Cl(2) is 2.792(1)A. Pyridoxal fragment is coordinated
      in its zwitterionic form. In addition to the X-ray structural analysis, the
      complex was characterized by IR spectrometric, conductometric and magnetic
      techniques, and the ligand itself by IR, 1H and 13C NMR spectra.

PMID- 17544152
TI  - The human mirror system: a motor resonance theory of mind-reading.
AB  - Electrophysiological data confirm the existence of neurons that respond to both
      motor and sensory events in the macaque brain. These mirror neurons respond to
      execution and observation of goal-orientated actions. It has been suggested that
      they comprise a neural basis for encoding an internal representation of action.
      In this paper the evidence for a parallel system in humans is reviewed and the
      implications for human theory of mind processing are discussed. Different
      components of theory of mind are discussed; the evidence for mirror activity
      within subtypes is addressed. While there is substantial evidence for a human
      mirror system, there are weaknesses in the attempts to localize such a system in
      the brain. Preliminary evidence indicates that mirror neurons may be involved in
      theory of mind; however, these data by their very nature are reliant on the
      presence, and precise characterization, of the human mirror system.

PMID- 17544153
TI  - Efficient parameterization of MUAP signal for identification of MU and volume
      conductor characteristics using neural networks.
AB  - The motor unit action potential (MUAPs) shapes depend on the anatomy and the
      physiology of the contracted muscle. The aim of this work is the identification
      of some characteristics of the motor unit (MU) and the volume conductor, namely
      the MU depth, the innervation zone width and the thickness of fat and skin layers
      based on MUAP signal parameters. The relationship between these characteristics
      and MUAP parameters are non-linear and complex. Thus, the use of the neural
      networks approach becomes an efficient tool to put in evidence this relationship.
      We have used the similarity and the homogeneity of the parameter criterions to
      choose which parameters are appropriate for the extraction. Two identification
      systems are presented and compared, a global system and a separate one. In order
      to evaluate the performance of each system, we have tested them using several
      simulated MUAP signals corrupted with additive Gaussian noise at different signal
      to noise ratios (SNR). A new test is introduced in which the electrode radius,
      the bar electrode dimensions and inclination angles for the detection system,
      fixed during the training process, are changed.

PMID- 17544154
TI  - Manic symptoms and quality of life in bipolar disorder.
AB  - This study evaluates the influence of manic symptoms on quality of life in a
      sample of adult bipolar disorder (BD) patients. This was a cross-sectional study
      including 125 BD outpatients from a university-based program. All patients were
      diagnosed using the Structured Clinical Interview for DSM-IV for BD. Manic
      symptoms and quality of life were assessed using the Young Mania Rating Scale
      (YMRS) and the World Health Organization Quality of Life Instrument-Short Version
      (WHOQOL-BREF), respectively. In the unadjusted analysis using linear regression,
      the score of manic symptoms was inversely associated with scores of quality of
      life within the social domain of the WHOQOL. In the adjusted analysis, the score
      of manic symptoms was inversely associated with the social, physical, and
      psychological domains of the WHOQOL. In a separate analysis at the YMRS items,
      items 4 (irritability) and 5 (sleep) were associated with lower quality of life.

PMID- 17544155
TI  - Validation of putative reference genes for qRT-PCR normalization in tissues and
      blood from pigs infected with Actinobacillus pleuropneumoniae.
AB  - The quantitative real-time reverse transcriptase polymerase chain reaction (qRT
      PCR) is a sensitive and very efficient technique for quantification of gene
      expression. However, qRT-PCR relies on accurate normalization of gene expression
      data, as RNA recovery and cDNA synthesis efficiency might vary from sample to
      sample. In the present study, six putative reference genes were validated for
      normalization of gene expression in three different tissues and in white blood
      cells from pigs experimentally infected with the common respiratory pathogen
      Actinobacillus pleuropneumoniae. Two dedicated validation programs (geNorm and
      Normfinder) were used to rank the six reference genes from best to worst. qRT-PCR
      data for the proinflammatory cytokine IL-6 was normalized using the proposed
      genes from geNorm and Normfinder as well as the commonly used reference gene
      glyceraldehyde-3-phosphate dehydrogenase (GAPDH). IL-6 expression was quantified
      in white blood cells, liver, lymph nodes and tonsils from 10 infected pigs and 5
      control pigs. After normalization using either geNorm or Normfinder IL-6 was
      shown to be significantly up-regulated (P<0.05) in all of the tissues from
      infected animals compared to non-infected control animals with a good agreement
      of expression differences between the two programs. On the contrary,
      normalization of IL-6 expression data from blood using GAPDH rendered the
      difference between infected and non-infected groups non-significant, and resulted
      in significantly different values compared to geNorm (P=0.01). Based on these
      results, we recommend to validate putative reference genes before normalization.

PMID- 17544156
TI  - The effect of dexamethasone on postoperative vomiting and oral intake after
      adenotonsillectomy.
AB  - OBJECTIVE: Vomiting is one of the most important postoperative complications of
      adenotonsillectomy. This study was designed to determine the effectiveness of
      preoperative intravenous dexamethasone on postoperative emesis. METHODS: In a
      double-blind, placebo-controlled clinical trial, 100 patients aged 5-15 years,
      ASA classes I and II were randomly selected to receive either 0.5 mg/kg IV
      dexamethasone (n=50), as study group or an equivalent volume of saline
      preoperatively, as control group. The anesthetic regimen and surgical procedures
      were standardized for all patients. The incidence of early and late vomiting, the
      time to first oral intake and duration of intravenous hydration were compared in
      both groups. RESULTS: Data analysis showed that the overall incidence of early
      and late vomiting was significantly lesser in dexamehasone group than the control
      one. The time to first oral intake and duration of IV therapy were also
      significantly shorter in dexamethasone group. CONCLUSION: A single dose of
      dexamethasone significantly decreased the incidence of postoperative vomiting in
      early and late recovery phase and shortened the time to first oral intake and the
      duration of IV therapy.

PMID- 17544157
TI  - rCBF to the hippocampal complex covaries with superior semantic memory retrieval.
AB  - The study of medial-temporal amnesics has established that much of the brain's
      store of general knowledge can be retrieved without the hippocampus. Several
      brain imaging studies, however, have reported that the hippocampus is active
      during the performance of semantic memory tasks. Although this activity may
      reflect memory encoding, it is also possible that it is due to the process of
      retrieving the semantic representations of the stimuli. Here we show in two
      H(2)(15)O positron emission tomography studies that cerebral blood flow (CBF) to
      the hippocampus covaries with superior performance during the retrieval of
      general knowledge. Left hippocampal CBF was associated with faster word meaning
      retrieval and right hippocampal CBF with better picture naming. A follow-up
      experiment failed to show that faster responding in the word meaning task was
      associated with better episodic memory for the stimuli and so weakens the
      proposal that the hippocampal activity was strictly related to memory encoding.
      In both experiments CBF to the lateral temporal cortex covaried with hippocampal
      CBF in a way that suggests that the hippocampus provides complementary support to
      activation within the association cortex.

PMID- 17544158
TI  - The effects of willed movement therapy on AMPA receptor properties for adult rat
      following focal cerebral ischemia.
AB  - BACKGROUND AND PURPOSE: Although we demonstrated willed movement (WM) therapy can
      facilitate the patients actively participating in the physical activities by
      cognitive and perceptual stimulation in our previous study, the molecular
      mechanisms of the willed movement on the patients remains unclear. We initially
      established the model of WM intervention for rats and identified possible effects
      of willed movement on motor recovery and on expression of Kainate/alpha-amino-3
      hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors in ischemia core (IC)
      and ischemia penumbra (IP) regions of rats after cerebral ischemia reperfusion.
      METHODS: Seventy-two adult male Sprague Dawley rats after successful 120-min
      period of occlusion of the left middle cerebral artery were selected and randomly
      divided into three groups: middle cerebral artery occlusion (MCAO), WM and
      environmental modification (EM). Neurological and neurobehavioral assessments
      were performed and the rats were killed at various recirculation times after
      MCAO. Reverse transcription-PCR were used to detect mRNA of GluR1-GluR4 subunit
      of AMPA receptors in the areas of IC and IP in all adult rats. RESULTS: Rats
      following WM intervention showed significantly better acquisition of climbing
      (every time point tested), forelimb mobility and neurological functions at
      subacute stage of MCAO. No difference was found in the expression levels of GluR1
      GluR4 mRNA among three groups in IC region. However, GluR1 and GluR4 mRNA of rats
      in group WM were significantly upregulated as compared with rats in group MCAO
      and group EM in IP region at subacute stage. CONCLUSIONS: Early willed movement
      treatment can increase the expression level of AMPA receptor subunits and thus
      might increase synaptic transmission and enhance brain plasticity after focal
      brain ischemia at the subacute stage.

PMID- 17544159
TI  - Chronic pharmacological treatment in takotsubo cardiomyopathy.
AB  - BACKGROUND: Takotsubo cardiomyopathy is a disorder that has been appreciated only
      recently. In most of reported cases, this syndrome mimes an acute myocardial
      infarction. Till this moment no data are available from literature about the
      treatment in the acute phase of this disease. AIM OF THE STUDY: In our
      multicentric experience we have retrospectively looked at the benefits of a
      treatment with ACE-inhibitors, beta-blockers, Aspirin and calcium channels
      blockers, started until the early phases of the disease and continued for 30
      days, in 36 patients affected by Takotsubo cardiomyopathy. We chose as endpoint
      of the study the efficacy of the used drug in improving left ventricular
      myocardial function and the rapidity of the effects of the same drug.bethods:
      from an international registry about the Takotsubo cardiomiopathy, co-ordinate by
      our research group, we evaluated the long term efficacy of some drugs,
      administrated like single treatment in some patients. RESULTS: Obtained data did
      not show any statistically significant difference in the percentages of
      improvement in the left ventricle ejection fraction evaluated at the admission to
      the hospital, before the discharge and after 30 days of treatment between each
      treated group and the control group of non-treated patients. No significant
      differences were found in hospitalization times between treated patients and
      controls. None of our patients experienced during the observation period a
      relapse of the disease. CONCLUSIONS: The results of our survey suggest that a
      chronic treatment with beta-blockers, ACE-inhibitors, calcium channels blockers
      and aspirin does not provide any benefit in patients with Takotsubo
      cardiomyopathy. Thus, it seem to be important an early correct differential
      diagnosis to avoid any chronic treatment in these patients.

PMID- 17544160
TI  - The application of risk analysis in aquatic animal health management.
AB  - Risk analysis has only been regularly used in the management of aquatic animal
      health in recent years. The Agreement on the Application of Sanitary and
      Phytosanitary measures (SPS) stimulated the application of risk analysis to
      investigate disease risks associated with international trade (import risk
      analysis-IRA). A majority (9 of 17) of the risk analyses reviewed were IRA. The
      other major focus has been the parasite of Atlantic salmon--Gyrodactylus salaris.
      Six studies investigated the spread of this parasite, between countries, rivers
      and from farmed to wild stocks, and clearly demonstrated that risk analysis can
      support aquatic animal health policy development, from international trade and
      biosecurity to disease interaction between wild and farmed stocks. Other
      applications of risk analysis included the spread of vertically transmitted
      pathogens and disease emergence in aquaculture. The Covello-Merkhofer, risk
      analysis model was most commonly used and appears to be a flexible tool not only
      for IRA but also the investigation of disease spread in other contexts. The
      limitations of the identified risk assessments were discussed. A majority were
      qualitative, partly due to the lack of data for quantitative analysis, and this,
      it can be argued, constrained their usefulness for trade purposes (i.e. setting
      appropriate sanitary measures); in other instances, a qualitative result was
      found to be adequate for decision making. A lack of information about the disease
      hazards of the large number of fish species traded is likely to constrain
      quantitative analysis for a number of years. The consequence assessment element
      of a risk analysis was most likely to be omitted, or limited in scope and depth,
      rarely extending beyond examining the evidence of susceptibility of farmed and
      wild species to the identified hazard. The reasons for this are discussed and
      recommendations made to develop guidelines for a consistent, systematic and multi
      disciplinary approach to consequence assessment. Risk analysis has improved
      decision making in aquatic animal health management by providing a transparent
      method for using the available scientific information. The lack of data is the
      main constraint to the application of risk analysis in aquatic animal health. The
      identification of critical parameters is an important output from risk analysis
      models which should be used to prioritise research.

PMID- 17544161
TI  - Molecular monitoring of disinfection efficacy using propidium monoazide in
      combination with quantitative PCR.
AB  - One of the major drawbacks of DNA-based microbial diagnostics is its inability to
      discriminate between live and dead bacteria. Due to the persistence of DNA in the
      environment after cells have lost their viability, DNA-based assays cannot assess
      pathogenic risk since signals can originate from both live and dead cells.
      Presented here is a potential application of the novel chemical propidium
      monoazide (PMA), which results in the selective suppression of DNA detection from
      dead cells. PMA can only penetrate dead cells with permeabilized cell membranes.
      Upon intercalation into the DNA, covalent crosslinkage of PMA to DNA is achieved
      through light exposure. This modification prevents the DNA from being amplified
      by PCR. The method, in combination with quantitative PCR as a diagnostic tool,
      successfully monitored the disinfection efficacy of hypochlorite, benzalkonium
      and heat on several model pathogens. Threshold cycle numbers increased with
      increasing disinfection strength after PMA treatment of samples compared to non
      PMA treated samples. With some disinfectant-specific differences, monitoring
      viability loss with membrane integrity as an indicator seemed to be more
      conservative than monitoring viability loss with plate counts. Loss of viability
      after short UV-exposure could not be monitored with PMA as UV light affects
      viability by inducing DNA damage without directly affecting membrane
      permeability.

PMID- 17544162
TI  - Environmental noise-exposed workers: event-related potentials, neuropsychological
      and mood assessment.
AB  - Prolonged environmental noise exposure can induce pathogenic effects on various
      physical and psychosocial responses. The first aim of this study was to
      investigate whether long-term occupational noise exposure could affect
      neurophysiological, neuropsychological and emotional statuses, with particular
      respect to attention and working memory. The second aim was to evaluate the
      effects on the tactile P300 of a specific stressor (background traffic noise) vs
      a non-specific stress inductor (Stroop test). The comparison between a group of
      noise-exposed workers (traffic police officers), and a control group (office
      employees) did not show marked differences in cognitive and emotional profiles.
      The amplitude of the baseline cognitive potential (P300), recorded during a
      tactile (electric) discrimination task, resulted higher in noise-exposed workers
      than in controls, and this enhancement was associated with a lower level of trait
      anxiety and better mood profiles. Moreover, we found a wider P300 amplitude
      reduction in traffic police officers than in controls, under noisy conditions due
      to traffic. The effect of the Stroop test as a stress inductor was negligible and
      similar in the two groups. The wider amplitude of the non-auditory P300 in
      traffic police officers in the baseline condition could be a sign of cross-modal
      cerebral plasticity enhancing attentive processes in the 'stress-free' sensory
      channel. In addition, noise-exposed workers presented a higher cerebral
      sensitivity to stress selectively when they were exposed to the habitual
      environmental stressor.

PMID- 17544163
TI  - The role of p21cip1 in adaptation of CHO cells to suspension and protein-free
      culture.
AB  - The up-regulation of cyclin-dependent kinase inhibitor p21 has been shown to
      enhance productivity of monoclonal antibodies and has been linked to various
      regulatory processes. To identify the potential role of p21 in adaptation to
      suspension and protein-free cultures, we studied the survival and growth of
      anchorage- and serum-dependent CHO cell lines that differed only in the period of
      p21-induced arrest. p21 overexpression led to rapid adaptation of cells to
      suspension and protein-free cultures. The period taken to achieve adaptation was
      correlated with the time the cells were arrested after transfer from the
      monolayer and serum-fed culture. Interestingly, cell aggregation associated with
      protein-free suspension culture was reduced in p21 culture in response to the
      loss of cellular adherence. The processes of adaptation to suspension and arrest
      did not decrease monoclonal antibody productivity. In contrast, following
      adaptation to protein-free growth media, an overall increase in specific
      productivity was observed. The ability of cells to survive in protein-free
      suspension cultures was due to the requirement of G1 cells to growth factors and
      to their relatively high resistance to the hydrodynamic forces. This improved
      process has the advantage of reducing the duration of critical path activity for
      developing CHO commercial cell lines from 72 to 36 days.

PMID- 17544165
TI  - Lipid nanoparticles for improved topical application of drugs for skin diseases.
AB  - Due to the lower risk of systemic side effects topical treatment of skin disease
      appears favourable, yet the stratum corneum counteracts the penetration of
      xenobiotics into viable skin. Particulate carrier systems may mean an option to
      improve dermal penetration. Since epidermal lipids are found in high amounts
      within the penetration barrier, lipid carriers attaching themselves to the skin
      surface and allowing lipid exchange between the outermost layers of the stratum
      corneum and the carrier appear promising. Besides liposomes, solid lipid
      nanoparticles (SLN) and nanostructured lipid carriers (NLC) have been studied
      intensively. Here we describe the potential of these carrier systems and compare
      the dermal uptake from SLN and NLC to the one of alternative vehicle systems. A
      special focus is upon the interactions of active ingredients and the lipid matrix
      as well as the quantification of dermal penetration.

PMID- 17544166
TI  - The combined use of VIGI@ct (bioMerieux) and fluorescent amplified length
      fragment polymorphisms in the investigation of potential outbreaks.
AB  - Even with good surveillance programmes, hospital-acquired infections (HAIs) are
      not always recognized and this may lead to an outbreak. In order to reduce this
      risk, we propose a model for prompt detection of HAIs, based on the use of a real
      time epidemiological information system called VIGI@ct (bioMerieux, Las Balmas,
      France) and on the rapid confirmation or exclusion of the genetic relationship
      among pathogens using fluorescent amplified length fragment polymorphism (f-AFLP)
      microbial fingerprinting. We present the results of one year's experience with
      the system, which identified a total of 306 suspicious HAIs. Of these, 281 (92%)
      were 'confirmed' by clinical evidence, 16 (5%) were considered to be simple
      colonization and the latter nine (3%) were archived as 'not answered' because of
      the absence of the physician's cooperation. There were seven suspected outbreaks;
      of these, f-AFLP analysis confirmed the clonal relationship among the isolates in
      four cases: outbreak 1 (four isolates of Pseudomonas aeruginosa), outbreak 2
      (three Escherichia coli isolates), outbreak 6 (two Candida parapsilosis isolates)
      and outbreak 7 (30 ESbetaL-producing Klebsiella pneumoniae subsp. pneumoniae).
      Based on our results, we conclude that the combination of VIGI@ct and f-AFLP is
      useful in the rapid assessment of an outbreak due to Gram-positive or Gram
      negative bacteria and yeasts.

PMID- 17544167
TI  - Promotion of hand hygiene techniques through use of a surveillance tool.
AB  - Effective hand hygiene practice in a clinical healthcare setting is the most
      effective means to prevent, control and reduce healthcare-associated infections.
      Despite the introduction of hand hygiene practices and targeted campaigns,
      surveillance to ensure implementation of these techniques remains limited.
      Surveillance is widely accepted as an essential component to infection control
      campaigns. Therefore, we sought to design and test an easy-to-use surveillance
      instrument for hospital hand hygiene developed and piloted for three months in
      nine hospitals in China. This paper presents the resulting hand hygiene
      surveillance instrument as well as explicit guidelines for its implementation.

PMID- 17544168
TI  - Efficacy of oral chlorhexidine in preventing lower respiratory tract infections.
      Meta-analysis of randomized controlled trials.
AB  - Several randomized controlled trials (RCTs) have examined the influence of oral
      chlorhexidine (CHX) in preventing nosocomial lower respiratory tract infection
      (LRTI). Most have failed to demonstrate a reduction in the incidence of LRTI. The
      present meta-analysis summarizes the effect of oral CHX on the development of
      LRTI. RCTs were identified through searching PubMed, MEDLINE and the Cochrane
      Central Register of Controlled Trials databases. Those describing the use of
      chlorhexidine for oral decontamination and reporting the incidence of LRTI as a
      study outcome were included in the meta-analysis. Seven RCTs met the inclusion
      criteria; pooling the results from these reveals a reduction in the relative risk
      (RR) of LRTI in the CHX group [RR(random): 0.58, 95% confidence interval (CI):
      0.45-0.74; and RR(fixed): 0.56, CI95: 0.44-0.72, respectively]. Further analyses
      showed that this result applied only to patients ventilated for up to 48h
      (RR(random): 0.58, CI95: 0.45-0.74; and RR(fixed): 0.56, 95% CI: 0.44-0.72). Oral
      CHX should be included among preventive measures performed to reduce nosocomial
      LRTI. Whether it has an impact on the development of LRTI in patients requiring
      mechanical ventilation for a longer period of time remains unresolved.

PMID- 17544169
TI  - Vasoactive intestinal peptide enhances growth and angiogenesis of human
      experimental prostate cancer in a xenograft model.
AB  - We show that vasoactive intestinal peptide (VIP) exerts trophic and proangiogenic
      activities in experimental prostate cancer in vivo. Nude mice were subcutaneously
      injected with Matrigel impregnated with LNCaP prostate cancer cells. Cell
      treatment with 100 nM VIP for 1h before xenograft resulted in increased tumor
      growth after 8 and, more remarkably, 15 days of injection. The same occurred with
      the mRNA expression of the main angiogenic factor, vascular endothelial growth
      factor (VEGF), as shown by real-time RT-PCR quantification. The proangiogenic
      activity of VIP was further established by showing increases of hemoglobin
      levels, Masson trichromic staining, and immunohistochemical CD34 staining in
      tumors excised 15 days after subcutaneous injection of VIP-treated cells as
      compared to control conditions. All these parameters indicate that VIP increases
      vessel formation. This xenograft model is a useful tool to study in vivo the
      effects of VIP-related peptides in tumor growth and development of blood supply
      as well as their therapeutical potential in prostate cancer.

PMID- 17544170
TI  - Neurotrophic effects of PACAP in the cerebellar cortex.
AB  - In the rodent cerebellum, PACAP is expressed by Purkinje neurons and PAC1
      receptors are present on granule cells during both the development period and in
      adulthood. Treatment of granule neurons with PACAP inhibits proliferation, slows
      migration, promotes survival and induces differentiation. PACAP also protects
      cerebellar granule cells against the deleterious effects of neurotoxic agents.
      Most of the neurotrophic effects of PACAP are mediated through the cAMP/PKA
      signaling pathway and often involve the ERK MAPkinase. Caspase-3 is one of the
      key enzymes implicated in the neuroprotective action of PACAP but PACAP also
      inhibits caspase-9 activity and increases Bcl-2 expression. PACAP and functional
      PAC1 receptors are expressed in the monkey and human cerebellar cortex with a
      pattern of expression very similar to that described in rodents, suggesting that
      PACAP could also exert neurodevelopmental and neuroprotective functions in the
      cerebellum of primates including human.

PMID- 17544171
TI  - Regeneration-based therapies for spinal cord injuries.
AB  - Although it has been long believed that the damaged central nervous system does
      not regenerate upon injury, there is an emerging hope for regeneration-based
      therapy of the damaged central nervous system (CNS) due to the progress of
      developmental biology and regenerative medicine including stem cell biology. In
      this review, we have summarized recent studies aimed at the development of
      regeneration-based therapeutic approaches for spinal cord injuries, including
      therapy with anti-inflammatory cytokines, transplantation of neural
      stem/precursor cells and induction of axonal regeneration.

PMID- 17544172
TI  - Abeta inhibits the proteasome and enhances amyloid and tau accumulation.
AB  - The accumulation of misfolded protein aggregates is a common feature of numerous
      neurodegenerative disorders including Alzheimer disease (AD). Here, we examined
      the effects of different assembly states of amyloid beta (Abeta) on proteasome
      function. We find that Abeta oligomers, but not monomers, inhibit the proteasome
      in vitro. In young 3xTg-AD mice, we observed impaired proteasome activity that
      correlates with the detection of intraneuronal Abeta oligomers. Blocking
      proteasome function in pre-pathological 3xTg-AD mice with specific inhibitors
      causes a marked increase in Abeta and tau accumulation, highlighting the adverse
      consequences of impaired proteasome activity for AD. Lastly, we show that Abeta
      immunotherapy in the 3xTg-AD mice reduces Abeta oligomers and reverses the
      deficits in proteasome activity. Taken together, our results indicate that Abeta
      oligomers impair proteasome activity, contributing to the age-related
      pathological accumulation of Abeta and tau. These findings provide further
      evidence that the proteasome represents a viable target for therapeutic
      intervention in AD.

PMID- 17544173
TI  - Neocortical glial cell numbers in human brains.
AB  - Stereological cell counting was applied to post-mortem neocortices of human
      brains from 31 normal individuals, age 18-93 years, 18 females (average age 65
      years, range 18-93) and 13 males (average age 57 years, range 19-87). The cells
      were differentiated in astrocytes, oligodendrocytes, microglia and neurons and
      counting were done in each of the four lobes. The study showed that the different
      subpopulations of glial cells behave differently as a function of age; the number
      of oligodendrocytes showed a significant 27% decrease over adult life and a
      strong correlation to the total number of neurons while the total astrocyte
      number is constant through life; finally males have a 28% higher number of
      neocortical glial cells and a 19% higher neocortical neuron number than females.
      The overall total number of neocortical neurons and glial cells was 49.3 billion
      in females and 65.2 billion in males, a difference of 24% with a high biological
      variance. These numbers can serve as reference values in quantitative studies of
      the human neocortex.

PMID- 17544174
TI  - Synthesis, characterization and in vitro release studies of a new acetazolamide
      HP-beta-CD-TEA inclusion complex.
AB  - The aim of our work was to develop a multicomponent inclusion complex of
      acetazolamide (ACZ) in order to investigate the combined effect of hydroxypropyl
      beta-cyclodextrin (HP-beta-CD) and triethanolamine (TEA) on the solubility of ACZ
      and its possibility of ophthalmic delivery. Phase solubility study was used to
      evaluate the complexation in solution at 25 degrees C. Complex formation was also
      evaluated by comparing the infrared (FT-IR) spectra of the solid complexes with a
      simple physical mixture containing the same amount of ACZ. FT-IR experiments
      provided data indicating that the carbonamido group of ACZ is involved in the
      inclusion process. In vitro release data showed that both formulations,
      containing the freeze-dried ternary complex and the corresponding simple physical
      mixture of ACZ with HP-beta-CD and TEA presented the fastest release rate of ACZ.
      These results suggest that the ACZ-HP-beta-CD-TEA complex represents an effective
      novel formulation to enhance ACZ solubility in water, turning it promising for
      ophthalmic administration.

PMID- 17544175
TI  - [An overdrainage].

PMID- 17544176
TI  - [Hypercalcaemia and malignant lymphoma. One case report].
AB  - Hypercalcaemia occurs in less than 15% of lymphomas but is associated with a poor
      prognosis. A patient known to have a testicular lymphoma was admitted because of
      asthenia and weight loss. Hypercalcemia and high serum level of calcitriol were
      found. A high-grade lymphoma attesting a Richter's syndrome was diagnosed.
      Palliative treatment consisting in corticosteroids and pamidronate was
      instituted. Hypercalcaemia in lymphoma has a poor prognosis and is often
      attributed to an acquired uncontrolled vitamin D 1-alpha-hydroxylase activity by
      the macrophages close to the lymphomatous cells. Influences of TNFalpha,
      interleukine 6 and PTHrp are also reported.

PMID- 17544177
TI  - [Acute renal failure following internal administration of povidone iodine: a case
      report].
AB  - INTRODUCTION: Using iodine povidone in internal way may be responsible of severe
      adverse effects, sometimes causing death of the patients. EXEGESE: A 36th years
      old woman, with a secondary sterility has benefitted of an uterine opacification
      by iodine povidone before a laparotomy and a salpingotomy. In post surgery she
      presented an anuric acute renal failure and a severe anaemia which have needed a
      transfusion. Outcome was favourable with a recuperation of diuresis and a full
      normalization of the renal function. CONCLUSION: The authors recommend to respect
      the indications of iodine povidone.

PMID- 17544178
TI  - When gene medication is also genetic modification--regulating DNA treatment.
AB  - The molecular methods used in DNA vaccination and gene therapy resemble in many
      ways the methods applied in genetic modification of organisms. In some regulatory
      regimes, this creates an overlap between 'gene medication' and genetic
      modification. In Norway, an animal injected with plasmid DNA, in the form of DNA
      vaccine or gene therapy, currently is viewed as being genetically modified for as
      long as the added DNA is present in the animal. However, regulating a DNA
      vaccinated animal as genetically modified creates both regulatory and practical
      challenges. It is also counter-intuitive to many biologists. Since immune
      responses can be elicited also to alter traits, the borderline between
      vaccination and the modification of properties is no longer distinct. In this
      paper, we discuss the background for the Norwegian interpretation and ways in
      which the regulatory challenge can be handled.

PMID- 17544179
TI  - Immunogenicity of Plasmodium vivax combination subunit vaccine formulated with
      human compatible adjuvants in mice.
AB  - An effective malaria vaccine will probably require the delivery of multiple
      antigens that induce several layers of immunity. Malaria antigens expressed on
      the surface and in apical organelles of blood-stage merozoites are potential
      vaccine candidates given their importance in the invasion of erythrocytes. The
      present study examined the kinetics of humoral response in BALB/c mice following
      immunization with combination of two blood-stage Plasmodium vivax invasion
      related molecules, the N-terminal, cysteine-rich region II of P. vivax Duffy
      binding protein (PvRII) and the 19kDa C-terminal region of merozoite surface
      protein 1 (PvMSP1(19)) formulated with Montanide ISA 720 and alhydrogel.
      Immunization with combination of recombinant PvRII and PvMSP1(19) formulated with
      the Montanide ISA 720 elicited higher antibody titer compared to the alhydrogel
      formulation. In case of both the adjuvants tested, combination of PvRII and
      PvMSP1(19) did not result in suppression of antibody response against either
      antigen when compared to immunization with individual antigens alone. Analysis of
      IgG subclasses showed that combination of both the recombinant proteins induced a
      mixed Th1/Th2-type response with almost all IgG subtypes being expressed in
      equivalent amount. Antibodies elicited against PvRII showed significant
      inhibitory effect on the binding of PvRII to recombinant Duffy antigen receptor
      for chemokines (DARC) in an in vitro binding assay. The results of the present
      study provide a rationale for a combination vaccine against P. vivax malaria
      based on PvMSP1(19) and PvRII.

PMID- 17544180
TI  - Identification by genomic immunization of a pool of DNA vaccine candidates that
      confer protective immunity in mice against Neisseria meningitidis serogroup B.
AB  - We have shown previously that expression library immunization is viable
      alternative approach to induce protective immunity against Neisseria meningitidis
      serogroup B. In this study we report that few rounds of library screening allow
      identification of protective pools of defined antigens. A previously reported
      protective meningococcal library (L8, with 600 clones) was screened and two sub
      libraries of 95 clones each were selected based on the induction of bactericidal
      and protective antibodies in BALB/c mice. After sequence analysis of each clone
      within these sub-libraries, we identified a pool of 20 individual antigens that
      induced protective immune responses in mice against N. meningitidis infection,
      and the observed protection was associated with the induction of bactericidal
      antibodies. Our studies demonstrate for the first time that ELI combined with
      sequence analysis is a powerful and efficient tool for identification of
      candidate antigens for use in a meningococcal vaccine.

PMID- 17544181
TI  - The annual impact of seasonal influenza in the US: measuring disease burden and
      costs.
AB  - BACKGROUND: Despite preventive efforts, influenza epidemics are responsible for
      substantial morbidity and mortality every year in the United States (US).
      Vaccination strategies to reduce disease burden have been implemented. However,
      no previous studies have systematically estimated the annual economic burden of
      influenza epidemics, an estimate necessary to guide policy makers effectively.
      OBJECTIVE: We estimate age- and risk-specific disease burden, and medical and
      indirect costs attributable to annual influenza epidemics in the United States.
      METHODS: Using a probabilistic model and publicly available epidemiological data
      we estimated the number of influenza-attributable cases leading to outpatient
      visits, hospitalization, and mortality, as well as time lost from work
      absenteeism or premature death. With data from health insurance claims and
      projections of either earnings or statistical life values, we then estimated
      healthcare resource utilization associated with influenza cases as were their
      medical and productivity (indirect) costs in $2003. RESULTS: Based on 2003 US
      population, we estimated that annual influenza epidemics resulted in an average
      of 610,660 life-years lost (undiscounted), 3.1 million hospitalized days, and
      31.4 million outpatient visits. Direct medical costs averaged $10.4 billion (95%
      confidence interval [C.I.], $4.1, $22.2) annually. Projected lost earnings due to
      illness and loss of life amounted to $16.3 billion (C.I., $8.7, $31.0) annually.
      The total economic burden of annual influenza epidemics using projected
      statistical life values amounted to $87.1 billion (C.I., $47.2, $149.5).
      CONCLUSIONS: These results highlight the enormous annual burden of influenza in
      the US. While hospitalization costs are important contributors, lost productivity
      from missed work days and lost lives comprise the bulk of the economic burden of
      influenza.

PMID- 17544182
TI  - The stability of human respiratory syncytial virus is enhanced by incorporation
      of the baculovirus GP64 protein.
AB  - Current efforts to develop a vaccine against human respiratory syncytial virus
      (HRSV) are focused on live attenuated strains. However, the unstable nature of
      HRSV is a major challenge for the preparation, storage and distribution of live
      vaccine candidates. We report here that the stability of HRSV can be improved by
      incorporation of the GP64 glycoprotein from baculovirus Autographa californica
      multiple nucleopolyhedrovirus. GP64 was incorporated in place of or in addition
      to the homologous HRSV glycoproteins and was either expressed from the HRSV
      genome or provided by propagating the virus in a Vero cell line constitutively
      expressing GP64 (Vbac cells). The infectivity of the different virus stocks was
      monitored after storage at 4 degrees, 22 degrees or 37 degrees C, over a period
      of 8 weeks. The results showed that the infectivity of HRSV could be stabilized
      by up to 10,000-fold by the GP64 protein, when stored at 22 degrees C for 6
      weeks. This approach for stabilizing live HRSV may be important for vaccine
      development and may also prove useful for stabilizing other enveloped viruses.

PMID- 17544183
TI  - Exposure of biota in the cooling pond of Ignalina NPP: hydrophytes.
AB  - The radiological assessment of non-human biota is now accepted by a number of
      international bodies. In this connection the scientific basis to assess and
      evaluate biota internal and external radiation exposure is required. This paper
      presents the comparison of freshwater biota (hydrophyte species) exposure due to
      discharged anthropogenic radionuclides with that due to natural background
      radiation. The radionuclides from Ignalina Nuclear Power Plant (Lithuania) are
      discharged into cooling pond - Druksiai Lake. Submerged hydrophytes were selected
      as biota exposure indicators because they represent the largest biomass in this
      lake and have comparatively high radionuclide activity concentrations. The
      detailed methodology evaluation of the submerged hydrophyte dose rate is
      presented. The ionizing radiation exposure dose rates to submerged hydrophyte
      roots and above sediment parts due to the major radionuclides ((54)Mn, (60)Co,
      (137)Cs, (90)Sr) discharged into the INPP cooling pond - Druksiai Lake were 0.044
      microGyh(-1) and 0.004 microGyh(-1), respectively. The internal exposure dose
      rate due to natural background alpha-emitters ((210)Po,(238)U, (226)Ra) was
      estimated to be 1.24 microGyh(-1), as compared with that of anthropogenic alpha
      emitter (240)Pu - 0.04 microGyh(-1), whereas the external exposure was 0.069
      microGyh(-1). The presented data deeper the knowledge about the concentration of
      radionuclides and submerged hydrophytes' exposure dose rates in European
      freshwater ecosystems.

PMID- 17544184
TI  - Impact of gamma irradiation on the transformation efficiency for extracellular
      plasmid DNA.
AB  - Extracellular DNA is omnipresent in aquatic environments and is thought to be a
      genetic material for horizontal gene transformation between microorganisms. We
      studied the impact of gamma irradiation on the transformation efficiency
      (transformants number per ng of DNA per ml) of extracellular DNA. Plasmid pEGFP
      as a model extracellular DNA was irradiated by gamma rays. The transformation
      efficiency decreased with the increase in radiation dose. A total dose of 10Gy is
      normally not lethal for microorganisms but certainly affects the transformation
      efficiency of extracellular DNA. The decrease in the efficiency would be induced
      by strand breaks of extracellular DNA because the yield of both single-strand
      breaks (SSBs) and double-strand breaks (DSBs) increased with the increase in
      radiation dose. The relative transformation efficiency of SSBs and DSBs to that
      of covalently closed circles (CCCs) was 30.3% and 0.2%, respectively. This impact
      on natural transformation suggests an inability of microorganisms to acquire new
      characteristics which should be normally acquired.

PMID- 17544185
TI  - Same day diagnosis of neck lumps using ultrasound-guided fine-needle core biopsy.

PMID- 17544186
TI  - IPCS: an integrated process control system for enhanced in-situ bioremediation.
AB  - To date, there has been little or no research related to process control of
      subsurface remediation systems. In this study, a framework to develop an
      integrated process control system for improving remediation efficiencies and
      reducing operating costs was proposed based on physical and numerical models,
      stepwise cluster analysis, non-linear optimization and artificial neural
      networks. Process control for enhanced in-situ bioremediation was accomplished
      through incorporating the developed forecasters and optimizers with methods of
      genetic algorithm and neural networks modeling. Application of the proposed
      approach to a bioremediation process in a pilot-scale system indicated that it
      was effective in dynamic optimization and real-time process control of the
      sophisticated bioremediation systems.

PMID- 17544187
TI  - Congener-specific accumulation and trophic transfer of polychlorinated biphenyls
      in spider crab food webs revealed by stable isotope analysis.
AB  - Polychlorobiphenyls (PCB) and stable isotopes (delta15N and delta13C) were
      analyzed in the spider crab (Maja brachydactyla) food web from the Iroise Sea
      (Western Brittany) and the Seine Bay (Eastern English Channel). PCB
      concentrations were all significantly higher in organisms from the Seine Bay than
      those from the Iroise Sea. PCB patterns were strongly related to the feeding mode
      of the species, and increased influence of higher chlorinated congeners was
      highlighted with trophic position of the organisms. PCB concentrations (lipid
      normalized) were significantly related to the isotopically derived trophic level
      (TL) in spider crab food webs. The highest trophic magnification factors (TMFs)
      were calculated for the congeners with 2,4,5-substitution, and were lower in the
      Seine Bay compared to the Iroise Sea. The confrontation of PCB and TL data also
      revealed biotransformation capacity of decapod crustaceans for specific congeners
      based on structure-activity relations.

PMID- 17544188
TI  - Borderline personality disorder and emotional responding: a review of the
      research literature.
AB  - Although problems with emotional functioning are considered central to borderline
      personality disorder (BPD), it is only recently that studies have begun utilizing
      laboratory biobehavioral measures (including neuroimaging and psychophysiological
      measures) to examine emotional responding in BPD. The application of basic
      science methodologies used in a systematic program of research to investigate
      clinically relevant phenomena, often called translational research, holds much
      promise in advancing the assessment and treatment of BPD. In this paper, we begin
      with an overview of the research on self-reported emotional responding in BPD.
      Next, we outline the advantages that translational research has over traditional
      self-report methodology in furthering an understanding of emotional responding in
      BPD, and review the extant laboratory studies of emotional responding in BPD.
      Finally, problems commonly encountered when conducting translational research on
      emotion in BPD are outlined, and solutions to these problems are offered.

PMID- 17544189
TI  - SARS and New York's Chinatown: the politics of risk and blame during an epidemic
      of fear.
AB  - This paper examines the production of risk and blame discourses during the 2003
      SARS epidemic and responses to those messages in New York City's Chinatown, a
      community stigmatized during the SARS epidemic despite having no SARS cases. The
      study consisted of 6 weeks participant observation and 37 semi-structured, open
      ended interviews with community members. Stigmatizing discourses from the late
      19th century resurfaced to blame Chinese culture and people for disease, and were
      recontextualized to fit contemporary local and global political-economic
      concerns. Many informants discursively distanced themselves from risk but
      simultaneously reaffirmed the association of Chinese culture with disease by
      redirecting such discourses onto recent Chinese immigrants. Legitimizing cultural
      blame obfuscates the structural and biological causes of epidemics and
      naturalizes health disparities in marginalized populations. This research
      demonstrates that myriad historical, political, and economic factors shape
      responses and risk perceptions during an unfamiliar epidemic, even in places
      without infection.

PMID- 17544190
TI  - Managing the work-life roller-coaster: private stress or public health issue?
AB  - Although research has established the importance for health of a sense of
      personal control at work, the implications of this for women have not been
      adequately studied. Using quantitative data from the Australian Longitudinal
      Study on Women's Health and qualitative data from an associated study, here we
      examine women's health and sense of control in relation to family and employment
      commitments. In line with other research, 'demand over-load' is found to be
      important for sense of control, but both 'over-load' and 'control' prove complex,
      as illustrated by the finding that good mental health is associated with
      satisfaction with, rather than actual, hours of employment. In the contemporary
      western context of longer working hours, increasing time strain, and gender
      relations shaped within a neo-liberal, individualised social environment, the
      findings suggest that as life speeds up, 'control' and the health effects of
      'busyness', need to be understood not merely as personal matters, but rather as
      potentially important public health issues.

PMID- 17544191
TI  - The contribution of migration to changes in the distribution of health over time:
      five-year follow-up study in Northern Ireland.
AB  - A number of recent studies have highlighted the potential contribution of
      migration to increasing inequalities in health between areas with different
      levels of deprivation. Some of these studies have reported that increasing
      inequalities between areas can, at least partly, be explained by selective
      migration. Both mortality and morbidity have been used as indicators of health
      status, but many of the studies focusing on morbidity have suffered from specific
      methodological problems, including the use of self-reported health measured after
      migration had occurred, thereby ignoring the possible effect that migration
      itself may have on health and the reporting of health. This study used general
      practice records assessed prior to movement, an arguably more objective measure
      of health status, from 40 general practices, to determine whether selective
      migration influenced the distribution of health in Northern Ireland between the
      years 2000 and 2005. Evidence of selective migration was found in the study, with
      migrants often having significantly different levels of health to non-migrants.
      However, overall migration within this cohort did not substantially alter the
      distribution of health through time, partly because the migrants out of the
      deprived and affluent areas were replaced by in-migrants with similar levels of
      health. The absence of an effect of migration in this instance should not be
      used, however, to conclude that migration effects are unimportant in assessing
      changes in inequalities through time. Rather, migration should be viewed in the
      context of the underlying population dynamics, which at the time of this study
      were characterised by a process of urban regeneration. Varying population
      movements, operating at different times and locations, require that the effects
      of migration be considered in all studies which examine changes in the spatial
      distribution of health.

PMID- 17544192
TI  - Patient cost sharing and social inequalities in access to health care in three
      western European countries.
AB  - This study evaluates the association between social class and health services use
      in France, Germany and Spain, three countries with universal health coverage but
      with different cost-sharing systems. In France, patients share the cost of both
      physician visits and hospitalization, in Germany they share the cost of
      hospitalization, and in Spain there is no system of patient cost sharing. The
      data were obtained from national health surveys carried out in each of these
      countries during the last decade of the 20th century. We found that persons
      belonging to a low social class had fewer physician visits than those belonging
      to a high social class in France, whereas the opposite occurred in Germany and
      Spain. After adjusting for a measure of the need for health care, the results in
      France changed little, whereas no significant differences by social class were
      seen in Germany and Spain. Persons of low social class had more hospital
      admissions than those of high social class in France and Spain, while no
      statistically different differences were seen in Germany. After adjusting for
      need, no significant differences were seen in any of the three countries.
      Although other factors related with the structure of the health system can not be
      ruled out, our findings suggest that patient cost sharing reduces the frequency
      of physician visits and that this decrease is greater in the low social classes,
      whereas the effect of co-payment for hospitalization on the frequency of hospital
      admission is not clear.

PMID- 17544193
TI  - Khat use and mental illness: a critical review.
AB  - Khat has been used as a stimulant plant in many parts of Africa and the Arabian
      Peninsula for centuries. Its current use among particular migrant communities in
      Europe and elsewhere has caused alarm among policy makers and health care
      professionals. In the United Kingdom, the debate over the psychiatric and social
      implications of khat use has led to a demand for stricter legal control of this
      stimulant plant. This paper (a) provides a historical overview of khat use, and
      (b) reviews the evidence for the existence of a causal link between khat use and
      mental illness. To do so, we undertook a detailed search of social and medical
      science databases for case reports, qualitative and quantitative articles on khat
      use and mental illness from 1945 to 2006. The validity and reliability of the
      studies that met our inclusion criteria were examined. Lastly, although
      highlighting health concerns about khat use we suggest that the debate about this
      popular drug in migrant populations carries elements of a 'moral panic'. There is
      a need for improved research on khat use and its possible association with
      psychiatric disorders.

PMID- 17544194
TI  - Organisational determinants of the use of physical restraints: a multilevel
      approach.
AB  - This paper reports a study of the relationship between the use of physical
      restraints with psycho-geriatric nursing home residents and the characteristics
      of organisations and residents. It is hypothesised that impairment in residents
      and organisational characteristics, such as a high workload of nursing staff and
      a low full-time equivalent (FTE) ratio on the wards, are associated with
      increased restraint use. In a cross-sectional study involving 15 Dutch psycho
      geriatric nursing home wards, 432 residents were selected for participation, of
      which 371 actually participated. Restraint status was measured using
      observations. Other resident characteristics, such as cognitive status, were
      determined using the Minimum Data Set (MDS). Job characteristics, such as
      workload, were determined by different self-reported measures. Characteristics of
      the wards, such as the FTE ratio, were derived from the registration system of
      the wards. Physical restraints were used with 56% of the psycho-geriatric nursing
      home residents. Bivariate analysis showed that job and ward characteristics were
      not associated with restraint use. Bivariate and multilevel analysis showed that
      residents' characteristics, such as mobility and cognitive status were
      significantly associated with restraint use. Furthermore, multilevel analysis
      showed that higher job autonomy experienced by nursing staff and a higher FTE
      ratio on the wards were also associated with increased restraint use. In
      conclusion, job and ward characteristics were not as strongly associated as
      residents' characteristics with restraint use. Impairments in residents, such as
      immobility, were strongly related to the use of restraints. Therefore, education
      and support of nursing staff in caring for psycho-geriatric nursing home
      residents with poor mobility is recommended to reduce the use of physical
      restraints in nursing homes.

PMID- 17544195
TI  - Influence of chronic cocaine treatment and sleep deprivation on sexual behavior
      and neurogenesis of the male rat.
AB  - The present study investigated the influence of chronic cocaine treatment on
      genital reflexes associated with paradoxical sleep deprivation (PSD), and
      possible alterations in hippocampus neurogenesis of the male rat. At 21 days of
      age, the rats were distributed into two groups and injected with saline or
      cocaine (7 mg/kg, three times a week for 12 weeks). At age 90 days, they were
      submitted to a four-day period of PSD (PSD groups) or maintained in home-cages
      (control groups), challenged with saline or cocaine administration, and placed in
      observation cages to assess genital reflexes. Two additional groups were used to
      quantify neurogenesis. PSD rats treated chronically with cocaine and challenged
      with saline did not differ from their respective control groups. The association
      of PSD with cocaine potentiated penile erection (PE) when compared to PSD-saline
      (saline challenged) rats, and these effects were similar to those observed in
      long-term cocaine treated rats. The bromodeoxyuridine (BrdU) assay indicated a
      reduction in BrdU-positive cells in the adult hippocampus after chronic cocaine
      treatment. These findings show that long-term cocaine treatment from brain
      development through adulthood had a marked effect on sexual responses and
      neuronal proliferation.

PMID- 17544196
TI  - In vitro study assessing apical leakage of sealer-only backfills in root canals
      of primary teeth.
AB  - AIM: To assess the sealing ability of zinc oxide-eugenol (ZOE), Apexit, and
      Sealapex used as sealer-only backfills in root canals of primary teeth using the
      high-pressure replica technique. METHODOLOGY: Two hundred and seventy root canals
      of deciduous molars as well as primary anterior teeth were randomly assigned to
      three groups (n=90). Root canals were prepared to size 35 and filled with either
      zinc oxide-eugenol (ZOE), Apexit, or Sealapex using a lentulo filler. Twenty-four
      hours after setting of the materials the roots were nail-varnished (except for
      the apical tip), and half of the specimens (n=45) were penetrated by a coloured
      (rhodamine B) epoxy resin. The resin was infiltated into the pores and cavities
      of the teeth in a high-pressure vessel. The remaining groups (n=45) were stored
      in 100% humidity, and infiltration of the resin followed after 40d. Apical
      leakage was assessed by means of a grinding technique using eight steps of 0.5mm
      each. RESULTS: ZOE and Apexit failed to seal the root canals in both subgroups.
      This was significantly different from the root canals filled with Sealapex where
      in both subgroups some 30% of the specimens revealed a tight seal up to a
      distance of 2.9mm of the apex. CONCLUSIONS: Under the conditions of this study it
      can be concluded that Sealapex shows less leakage than ZOE and Apexit. With
      regard to the three materials tested, Sealapex should be a viable alternative for
      sealer-only obturation of pulpectomized primary teeth. The high-pressure replica
      technique seems to be suitable for assessing leakage of root canal filling
      materials.

PMID- 17544197
TI  - Interferon, a growing cytokine family: 50 years of interferon research.
AB  - The establishment of an antiviral state in cells is the defining activity of
      interferons (IFNs) as well as the property that permitted their discovery in 1957
      by Isaacs and Lindenmann. In addition, interferons have other cellular functions
      that have potential clinical applications. Today, interferons are used for the
      treatment of a variety of malignancies and viral diseases. The publication of
      this special issue of Biochimie gives us a great opportunity to review the state
      of the art in knowledge about interferons and to explore possible future
      directions. This commentary text will introduce the reviews written by colleagues
      who are experts in different aspects of interferon research, to mark the 50th
      anniversary of the discovery of interferon.

PMID- 17544198
TI  - Cytosolic glutathione peroxidase from liver of pacu (Piaractus mesopotamicus), a
      hypoxia-tolerant fish of the Pantanal.
AB  - Pacu (Piaractus mesopotamicus Holmberg, 1887, Characiformes) dwells in waters of
      Pantanal, in which it has adapted for alternate concentrations of dissolved
      oxygen. Intracellular antioxidant protection should be vital for such an
      adaptation. Accordingly, we found that cytosol from liver of pacu has the highest
      antioxidant glutathione peroxidase activity so far reported for fish and murine
      species. To clarify whether this activity was due to a selenium independent
      glutathione S-transferase or to a glutathione peroxidase, we purified it and
      studied its kinetics. The substrates cumene hydroperoxide and hydrogen peroxide
      were promptly reduced by the enzyme, but peroxidized phosphatidylcholine had to
      undergo previous fatty acid removal with phospholipase A(2). Augmenting
      concentrations (from 2 to 6 mM) of reduced glutathione activated the pure enzyme.
      Curves of velocity versus different micromolar concentrations of hydrogen
      peroxide in the presence of 2, 4 or 8 mM reduced glutathione indicated that at
      least 2.5 mM reduced glutathione should be available in vivo for an efficient
      continuous destruction of micromolar concentrations of hydrogen peroxide by this
      peroxidase. Molecular exclusion HPLC and SDS-polyacrylamide gel electrophoresis
      indicated that the purified peroxidase is a homotetramer. Data from internal
      sequences showed selenocysteine in its primary structure and that the enzyme was
      a homologue of the type-1 glutathione peroxidase found in rat, bull, trout,
      flounder and zebra fish. Altogether, our data establish that in liver cells of
      pacu, a hypoxia-tolerant fish from South America, there are high levels of a
      cytosolic GPX-1 capable of quenching hydrogen peroxide and fatty acid peroxides,
      providing an effective antioxidant action.

PMID- 17544199
TI  - Disclosure and health-seeking behaviour following intimate partner violence
      before and during pregnancy in Flanders, Belgium: a survey surveillance study.
AB  - OBJECTIVES: The objectives were to estimate the prevalence of physical and sexual
      intimate partner violence (IPV) among a regional sample of the general obstetric
      population as the lifetime prevalence, as the 1-year period prevalence before
      pregnancy, and as the prevalence during the index pregnancy; to assess the rates
      of disclosure and help-seeking behaviour with IPV; and to determine the
      acceptability of screening for IPV. STUDY DESIGN: A multi-centred survey
      surveillance study was carried out among pregnant women attending five large
      hospitals in the province of East Flanders, Belgium as a regional probability
      sample of the general obstetric population. Data were collected through an
      anonymous, written questionnaire that included the Abuse Assessment Screen and
      additional questions on the circumstances of the most recent episode of physical
      or sexual violence, on disclosure and help-seeking behaviour, on reporting
      assault to the police, and on the acceptability of routine screening for IPV.
      RESULTS: The sampling frame consisted of 1362 women who received the
      questionnaire at the antenatal service during a 2-month study period, of which
      537 (mean age 29.4 years, S.D. 4.09) returned the envelope (response rate 39.4%).
      The lifetime prevalence of IPV was estimated to be 10.1% (95% CI 7.7-13.0%) and
      the period prevalence of IPV during pregnancy and/or in the year preceding
      pregnancy 3.4% (95% CI 2.1-5.4%). There was a significant difference in the
      reported lifetime prevalence of IPV between women attending with a partner and
      those who came to the prenatal visit unattended by their partner in particular
      (6.8% versus 13.9%, p=0.010). Overall, only 19.2% (23 out of 120) and as few as
      6.6% (4 out of 61) of the victims of physical and sexual abuse respectively
      sought medical care by consulting a general practitioner, gynaecologist, or an
      emergency department. Routine screening for IPV by a general practitioner or
      gynaecologist was found to be largely acceptable. CONCLUSIONS: In our highly
      medicalised society, women experiencing partner violence rarely disclose abuse to
      the widely available health care services, unless they are directly asked about
      it, which appears an acceptable practice. Hence, there is a definite need to
      improve women's awareness regarding abuse and their help-seeking behaviour at a
      public health level.

PMID- 17544200
TI  - The prohibitin 3' untranslated region polymorphism in patients with ovarian
      cancer.
AB  - OBJECTIVE: Prohibitin is an important antiproliferative protein inhibiting cell
      proliferation by blocking the G1/S transition of the cell cycle. Recent findings
      indicate that the presence of at least one mutant allele within a certain
      prohibitin gene polymorphism causes inactivation of bioactive RNA resulting in
      the loss of its pro-apoptotic function and a subsequent risk for malignant
      growth. Based on these findings we studied whether the presence of this
      prohibitin polymorphism increases the risk and worsens the prognosis of ovarian
      cancer in Caucasian women. STUDY DESIGN: A polymorphism within the 3'
      untranslated region (UTR) of the prohibitin gene was evaluated by pyrosequencing
      in 136 Caucasian patients with epithelial ovarian cancer and 129 healthy
      Caucasian controls. RESULTS: The wild-type C/C, heterozygous C/T, and the mutant
      T/T prohibitin genotype was found in 88 (64.7%), 46 (33.8%), and 2 (1.5%)
      patients with ovarian cancer and in 84 (65.1%), 39 (30.2%), and 6 (4.7%) healthy
      controls. Presence of at least one mutant allele of the prohibitin 3' UTR
      polymorphism was not associated with an increased risk of ovarian cancer as
      compared to healthy controls (P=0.9). No association was found between presence
      of the prohibitin 3' UTR polymorphism and the clinico-pathological parameters
      tumor stage, tumor grade, and patients' age at diagnosis. Presence of at least
      one mutant allele of the prohibitin 3' UTR polymorphism was not associated with
      disease-free and overall survival. CONCLUSION: The prohibitin 3' UTR polymorphism
      was not associated with risk and prognosis of ovarian cancer in Caucasian women.

PMID- 17544201
TI  - Good efficiency of intrauterine insemination programme for serodiscordant couples
      with HIV-1 infected male partner: a retrospective comparative study.
AB  - OBJECTIVE: Assisted reproduction techniques can minimize the risk of HIV female
      contamination when the male partner is HIV-infected. The aim of this study was to
      investigate the efficiency of sperm washing and intrauterine insemination (IUI)
      in these couples. STUDY DESIGN: Retrospective comparative study. Eighty-four HIV
      1 serodicordant couples underwent 294 IUI. The control group was composed of 90
      couples (320 IUI cycles) with donor sperm. Spermatozoa from HIV-1 infected male
      partner were prepared and tested for HIV-1 according to sperm washing method.
      Spermatozoa from HIV-1 and donor male were frozen before IUI. IUI were performed
      after ovarian stimulation. Main outcomes measures were pregnancy rate per cycle
      and baby take-home rate per couples. RESULTS: Although the pregnancy rate and
      baby take-home rate were higher in IUI with sperm washing than in IUI using donor
      sperm (18.0 versus 14.7 and 52.4 versus 41.1, respectively), the differences were
      not statistically significant. In serodiscordant couples, blood estradiol levels
      under ovarian stimulation and total motile sperm inseminated were a determining
      factor in achieving pregnancy. No female HIV-1 contamination occurred.
      CONCLUSION: This study demonstrates that sperm washing and IUI are highly
      effective in enabling serodiscordant couples with an HIV-1 infected male partner
      to have a child.

PMID- 17544202
TI  - Successful assisted reproduction in adult males with bladder extrophy-epispadias
      complex.

PMID- 17544203
TI  - Spatial distribution of dielectric shielding in the interior of Pyrococcus
      furiosus rubredoxin as sampled in the subnanosecond timeframe by hydrogen
      exchange.
AB  - Experimental pK values of ionizable sidechains provide the most direct test for
      models representing dielectric shielding within the interior of a protein.
      However, only the strongly shifted pK values are particularly useful for
      discriminating among models. NMR titration studies have usually found only one or
      two such shifted pK values in each protein, so that the fitting of the
      experimental data to a uniform internal dielectric (epsilon(int)) model is not
      well constrained. The observed variation among proteins for such epsilon(int)
      estimates may reflect nonuniformity of dielectric shielding within each protein
      interior or qualitative differences between individual proteins. The differential
      amide kinetic acidities for a series of metal-substituted rubredoxins are shown
      to be consistent with Poisson-Boltzmann predictions of dielectric shielding that
      is relatively uniform for all of the amides that are sensitive to the metal
      charge, a region which corresponds to roughly 1/3 of the internal volume. The
      effective epsilon(int) values near 6 that are found in this study are
      significantly lower than many such estimates derived from sidechain pK
      measurements. The differing timeframes in which dielectric relaxation can respond
      to the highly transient peptide anion as compared to the longer lived states of
      the charged sidechains offers an explanation for the lower apparent dielectric
      constant deduced from these measurements.

PMID- 17544204
TI  - The mountain-lowland debate: deforestation and sediment transport in the upper
      Ganga catchment.
AB  - The Himalaya-Gangetic Plain region is the iconic example of the debate about the
      impact on lowlands of upland land-use change. Some of the scientific aspects of
      this debate are revisited by using new techniques to examine the role of
      deforestation in erosion and river sediment transport. The approach is whole-of
      catchment, combining a history of deforestation with a history of sediment
      sources from well before deforestation. It is shown that deforestation had some
      effect on one very large erosional event in 1970, in the Alaknanda subcatchment
      of the Upper Ganga catchment, but that both deforestation and its effects on
      erosion and sediment transport are far from uniform in the Himalaya. Large
      magnitude erosional events occur for purely natural reasons. The impact on the
      Gangetic Plain of erosion caused by natural events and land cover change remains
      uncertain.

PMID- 17544205
TI  - Editorial comment on: The quality of life and hormonal disturbances in testicular
      cancer survivors in cisplatin era.

PMID- 17544206
TI  - The quality of life and hormonal disturbances in testicular cancer survivors in
      Cisplatin era.
AB  - OBJECTIVES: To assess the degree of hormonal abnormalities in testicular cancer
      survivors and the effect of these changes on patients' quality of life. METHODS:
      Men with complete remission of testicular cancer for over 2 yr were eligible.
      Patients completed the State-Trait Anxiety Inventory (STAI), the Hospital Anxiety
      and Depression Scale (HADS), Beck Depression Inventory (BDI), the International
      Index of Erectile Function (IIEF), and the Sexual Functioning Questionnaire
      (SFQ), and rated their physical and psychological well-being, quality of life,
      and relationship with their partner. Levels of the hormones testosterone,
      estradiol, thyreotropin, follicle-stimulating hormone (FSH), luteinizing hormone
      (LH), and prolactin were determined. Relationships between hormone levels and
      questionnaire results were assessed. RESULTS: A total of 326 men were tested, of
      whom 269 were treated with platinum-based chemotherapy. The most common endocrine
      abnormalities were above-normal gonadotropin levels (LH, 55%, and FSH, 49% of
      cases) and lowered testosterone (15%). Twenty-seven percent (STAI) and 28% (HADS)
      of the patients had abnormal anxiety levels, while the depression rate was 15%
      (BDI) and 18% (HADS); 40% of patients had erectile dysfunction. Linear regression
      analysis excluding the influence of age showed higher depression levels in the
      BDI among patients with elevated LH (p=0.010) or FSH (p=0.017). Patients with
      above-normal LH showed increased sexual problems in the SFQ (p=0.030). Elevated
      gonadotropins correlated with deteriorated physical well-being (p=0.028). Men
      with abnormal estradiol were more prone to erectile dysfunction (p=0.009).
      CONCLUSIONS: Hormonal abnormalities have a negative impact on the quality of life
      of testicular cancer survivors.

PMID- 17544207
TI  - Optimal length distribution of termite tunnel branches for efficient food search
      and resource transportation.
AB  - Subterranean termites excavate branching tunnels for searching and transporting
      food in soil. Experimentally, the length distribution of the branch tunnels,
      P(L), was characterized by the exponentially decaying function, P(L)
      approximately exp(-alphaL) with a branch length exponent of alpha=0.15. To
      evaluate the significance of this alpha value, we used a lattice model to
      simulate tunnels of the Formosan subterranean termite, Coptotermes formosanus
      Shiraki in featureless soil and computed the ratio of energy gain for obtained
      food to loss for transporting food for a given time, gamma for various simulated
      tunnel patterns with the different values of alpha. In simulation, the gamma was
      maximized at 0.15<alpha<0.20 for the number of primary tunnels N=6, 8, and 10.
      Our results indicate that tunnels with branch length distributions similar to
      those derived from empirical tunnel patterns result in tunnels made up of highly
      efficient paths to search and transport resources.

PMID- 17544208
TI  - Degradation characteristics of secondary effluent of domestic wastewater by
      combined process of ozonation and biofiltration.
AB  - The performance of the combined process of ozonation and biofiltration was
      studied for treating the secondary effluent from sewage treatment plant. It was
      found that COD, NH(3)-N, and TOC were removed from 40-52, 10-19, and 9-13 mg/L in
      the raw water to 18-23, 0.5-1.5, and 7-8.5 mg/L in the effluent water (removal
      efficiency were 58, 89, and 25%, respectively), respectively, with an ozone dose
      of 10 mg/L (0.7-1.1 mg O(3)/(mg TOC) and 0.2-0.25 mg O(3)/(mg COD)), and
      contacting time of 4 min. Under the operation conditions, ozonation enhanced the
      biodegradability of the organics in the secondary effluent, as illustrated by
      increasing biodegradable dissolved organic carbon (BDOC) value from 0.8-1.1 mg/L
      in the raw water to the 2.0-2.7 mg/L in the effluent water. Meanwhile, the
      percentage of the organics with molecular size less than 1k Da in the secondary
      effluent increased from 52.9 to 72.6%. The experimental results supported the
      expectation that the combined process of O(3)/Biofiltration might enhance the
      overall treatment efficiency of secondary effluent treatment.

PMID- 17544209
TI  - Effect of the impregnation of carbon cloth with ethylenediaminetetraacetic acid
      on its adsorption capacity for the adsorption of several metal ions.
AB  - Effect of loading of C-cloth with ethylenediaminetetraacetic acid (EDTA) on the
      adsorption capacity for the adsorption of several metal cations was studied. The
      concentration of ions in the solution was monitored using atomic absorption
      spectrometry. The adsorption isotherm data for the cations were derived at 25
      degrees C and treated according to Langmuir and Freundlich models and was found
      that for most of the investigated cations Langmuir model was more successful.
      Adsorption capacities determined from Langmuir isotherms. Loading of the
      adsorbent with EDTA increased the adsorption capacity for the adsorption of all
      of the investigation ions.

PMID- 17544210
TI  - Peripheral involvement of PKA and PKC in subcutaneous bee venom-induced
      persistent nociception, mechanical hyperalgesia, and inflammation in rats.
AB  - The roles of central protein kinases A and C (PKA and PKC) in various pain states
      have intensively been investigated during the past decade. The aim of the present
      study was to investigate the peripheral involvement of PKA and PKC in persistent
      nociceptive response, evoked pain behaviors, and inflammation induced by
      subcutaneous (s.c.) injection of bee venom (BV, 0.2mg/50 microl) in rats. The
      effects of intraplantar injection of H-89 (a PKA inhibitor, 5-100 microg/50
      microl) and chelerythrine chloride (a PKC inhibitor, 5-100 microg/50 microl) on
      BV-elicited persistent nociception (nociceptive flinching reflex), mechanical
      hyperalgesia, and inflammation were systematically investigated. Pre-treatment
      with H-89 dose-dependently inhibited only BV-induced mechanical hyperalgesia, but
      not the persistent nociception and inflammation. In contrast, pre-treatment with
      chelerythrine chloride dose-dependently inhibited BV-induced sustained
      nociception and inflammation, but not the mechanical hyperalgesia. Topical pre
      treatment of the sciatic nerve with 1% capsaicin significantly blocked the
      inhibitory effects of the PKC inhibitor on BV-induced inflammation, but not the
      persistent flinching response. These results indicate that peripheral PKA and PKC
      involvements in BV-induced pain behaviors differ, and capsaicin-sensitive
      afferents appear to participate in the pro-inflammatory role of PKC in the BV
      pain model. Findings from the present study also suggest that targeting specific
      peripheral protein kinases might prove effective in the treatment of persistent
      pain and inflammation.

PMID- 17544211
TI  - Influence of endometriosis on visceromotor and cardiovascular responses induced
      by vaginal distention in the rat.
AB  - This study examined pseudoaffective responses elicited by vaginal distention in
      urethane-anesthetized rats, and tested hypotheses that responses would be
      increased by endometriosis (ENDO) and vary with the estrous cycle. Three groups
      were studied: ENDO, shamENDO, and Naive. ENDO was induced by autotransplanting
      small pieces of uterine horn (or, for shamENDO, fat) on mesenteric arteries. Ten
      weeks later, rats in proestrus or metestrus were anesthetized with urethane.
      Distendable latex balloons were inserted into the vaginal canal. While an
      increasing series of vaginal distentions was delivered, changes in
      electromyographic activity of the external oblique musculature (visceromotor
      response, VMR) and mean arterial pressure (pressor) responses were simultaneously
      measured. Vaginal distention produced VMR and pressor responses in all groups.
      These responses were significantly greater in ENDO than in the other groups, and
      greater in proestrus than metestrus. Although the overall amount of cystic tissue
      was greater in proestrous than metestrous rats, there was no correlation between
      these amounts and VMR or pressor responses. Acute spinalization (T8-T9) and
      bilateral pelvic, but not hypogastric, neurectomy attenuated both VMR and pressor
      responses, supporting the hypothesis that vaginal nociception involves
      suprathoracic spinal processing of information conveyed by the pelvic nerve.
      These effects on VMR and pressor responses to vaginal distention parallel
      behavioral escape responses to the same stimuli reported previously. The findings
      encourage continued use of VMR and pressor responses for further investigation of
      mechanisms underlying pain associated with ENDO and its potential treatment.

PMID- 17544212
TI  - Mindfulness meditation for the treatment of chronic low back pain in older
      adults: a randomized controlled pilot study.
AB  - The objectives of this pilot study were to assess the feasibility of recruitment
      and adherence to an eight-session mindfulness meditation program for community
      dwelling older adults with chronic low back pain (CLBP) and to develop initial
      estimates of treatment effects. It was designed as a randomized, controlled
      clinical trial. Participants were 37 community-dwelling older adults aged 65
      years and older with CLBP of moderate intensity occurring daily or almost every
      day. Participants were randomized to an 8-week mindfulness-based meditation
      program or to a wait-list control group. Baseline, 8-week and 3-month follow-up
      measures of pain, physical function, and quality of life were assessed. Eighty
      nine older adults were screened and 37 found to be eligible and randomized within
      a 6-month period. The mean age of the sample was 74.9 years, 21/37 (57%) of
      participants were female and 33/37 (89%) were white. At the end of the
      intervention 30/37 (81%) participants completed 8-week assessments. Average class
      attendance of the intervention arm was 6.7 out of 8. They meditated an average of
      4.3 days a week and the average minutes per day was 31.6. Compared to the control
      group, the intervention group displayed significant improvement in the Chronic
      Pain Acceptance Questionnaire Total Score and Activities Engagement subscale
      (P=.008, P=.004) and SF-36 Physical Function (P=.03). An 8-week mindfulness-based
      meditation program is feasible for older adults with CLBP. The program may lead
      to improvement in pain acceptance and physical function.

PMID- 17544214
TI  - Electric force microscopy investigation of a MEH-PPV conjugated polymer blend:
      robustness or frailty?
AB  - Electric force microscopy (EFM) was employed in the electrical characterization
      of a blend of thermoplastic polyurethane (TPU) and poly(2-methoxy-5-(2'-ethyl
      hexyloxy)-1,4-phenylenevinylene) (MEH-PPV) conjugated polymer. Although
      qualitative EFM interpretation is straightforward, its quantitative analysis
      always relies on approximated models. The extraction of physically reasonable
      parameters is normally assumed as a proof of validity of the theoretical model
      employed. In order to gather information about electric properties of this blend
      and to test the EFM technique itself, two distinct and discordant models were
      developed in this work to fit experimental EFM data. Even though MEH-PPV is
      regarded as a conductor in one model and as a dielectric in the other, both
      models yielded coherent and reasonable electrical properties for this blend. Such
      unexpected results are used to discuss the robustness or frailty of EFM in the
      analysis of complex materials.

PMID- 17544215
TI  - Effect of sample bending on diffracted intensities observed in CBED patterns of
      plan view strained samples.
AB  - Convergent beam electron diffraction is used to study the effect of the sample
      bending on diffracted intensities as observed in transmission electron microscopy
      (TEM). Studied samples are made of thin strained semiconductor Ga(1-)(x)In(x)As
      epitaxial layers grown on a GaAs substrate and observed in plan view. Strong
      variations of the diffracted intensities are observed depending on the thinning
      process used for TEM foil preparation. For chemically thinned samples, strong
      bending of the substrate occurs, inducing modifications of both kinematical and
      dynamical Bragg lines. For mechanically thinned samples, bending of the substrate
      is negligible. Kinematical lines are unaffected whereas dynamical lines have
      slightly asymmetric intensities. We analyse these effects using finite element
      modelling to calculate the sample strain coupled with dynamical multibeam
      simulations for calculating the diffracted intensities. Our results correctly
      reproduce the qualitative features of experimental patterns, clearly
      demonstrating that inhomogeneous displacement fields along the electron beam
      within the substrate are responsible for the observed intensity modifications.

PMID- 17544216
TI  - Influence of calcium on direct incorporation of membrane proteins into in-plane
      lipid bilayer.
AB  - Reconstitution of transmembrane proteins by direct incorporation into supported
      lipid bilayers (SLBs) is a new method to provide suitable samples for high
      resolution atomic force microscopy (AFM) analysis of membrane proteins. First
      experiments have reported successful incorporation of proteins into detergent
      destabilized SLBs. Here, we analyzed by AFM the incorporation of membrane
      proteins in the presence of calcium, a divalent cation functionally important for
      several membrane proteins. Using lipid-phase-separated membranes, we first show
      that calcium strongly stabilizes the SLBs decreasing the insertion of low cmc
      detergents, dodecyl-beta-maltoside, dodecyl-beta-thiomaltoside, and N
      hexadecylphosphocholine (Fos-Choline-16) and further insertion of proteins.
      However, high yield of protein insertion is recovered in the presence of calcium
      by increasing the detergent concentration in the solution. These data revealed
      the importance of the calcium in the structure of SLBs and provided new insights
      into the mechanism of protein insertion into these model membranes.

PMID- 17544217
TI  - Preparation of biomolecule gel matrices for electron microscopy.
AB  - We report a new sample preparation method that allows the direct transmission
      electron microscopy evaluation of the architectural characteristics of
      biomolecules entrapped in gel matrices. We demonstrate that this sample
      preparation technique can be used for the identification and ultrastructural
      characterization of liposomes, collagen I and collagen III embedded in gel
      matrices, and has the potential to be useful for transmission electron microscopy
      (TEM) characterization of other biomolecule-gel matrix systems.

PMID- 17544218
TI  - Influence of culture conditions on Escherichia coli O157:H7 biofilm formation by
      atomic force microscopy.
AB  - Biofilms are complex microbial communities that are resistant against attacks by
      bacteriophages and removal by drugs and chemicals. In this study, biofilms of
      Escherichia coli O157:H7, a bacterial pathogen, were investigated using atomic
      force microscopy (AFM) in terms of the dynamic transition of morphology and
      surface properties of bacterial cells over the development of biofilms. The
      physical and topographical properties of biofilms are different, depending on
      nutrient availability. Compared to biofilms formed in a high nutrient medium,
      biofilms form faster and a higher number of bacterial cells were recovered on
      glass surface in a low nutrient medium. We demonstrate that AFM can obtain high
      resolution images and the elastic information about biofilms. As E. coli biofilm
      becomes mature, the magnitude of the force between a tip and the surface of the
      biofilm gets stronger, suggesting that extracellular polymeric substances (EPSs),
      sticky components of biofilms, accumulate over the surface of cells upon the
      initial attachment of bacterial cells to surfaces.

PMID- 17544219
TI  - Changes in the levels of eicosanoids in cats naturally and experimentally
      infected with Dirofilaria immitis.
AB  - Feline heartworm (Dirofilaria immitis) infection is a severe, life-threatening
      disease. The eicosanoids are lipid mediators derived from the metabolism of the
      arachidonic acid, involved in the regulation of the immune response and of
      inflammatory reactions. In this study, naturally infected cats showed significant
      higher levels of prostaglandin E(2) (PGE2), thromboxane B(2) (TXB(2)) and
      leukotriene B(4) (LTB4) than uninfected cats. Changes in the levels of
      eicosanoids during the infection were observed in experimentally infected cats.
      PGE2 increased significantly during the first 60 days post-infection, then
      progressively decreased until day 180 post-infection. At this time, PGE2 values
      are still significantly higher than those observed before the infection. TxB2 and
      LTB4 increased progressively from the beginning of infection and reached their
      maximum levels 180 days post-infection. In experimentally infected, ivermectin
      treated cats, 15 days after treatment (45 days after infection) both PGE2 and
      LTB4 levels were similar to those observed in experimentally infected, untreated
      cats. No significant differences of PGE2 levels were found before the infection
      and at the end of the experiment (165 days post-treatment, 195 days post
      infection). Increased levels of LTB4 were found 15 days post-treatment, afterward
      they progressively decreased. These data show that D. immitis infection
      influences the production of intravascular eicosanoids in cats. The high levels
      of PGE2 observed in the early phase of infection could be related to the survival
      of the worms, while those of TxB2 and LTB4 detected at the end of the study could
      mediate the inflammatory reactions and thrombi formation during the feline
      dirofilariosis.

PMID- 17544220
TI  - Lysophosphatidic acid prevents apoptosis of Caco-2 colon cancer cells via
      activation of mitogen-activated protein kinase and phosphorylation of Bad.
AB  - Lysophosphatidic acids (LPA) exert growth factor-like effects through specific G
      protein-coupled receptors. The presence of different LPA receptors often
      determines the specific signaling mechanisms and the physiological consequences
      of LPA in different environments. Among the four members of the LPA receptor
      family, LPA(2) has been shown to be overexpressed in colon cancer suggesting that
      the signaling by LPA(2) may potentiate growth and survival of tumor cells. In
      this study, we examined the effect of LPA on survival of colon cancer cells using
      Caco-2 cells as a cell model system. LPA rescued Caco-2 cells from apoptosis
      elicited by the chemotherapeutic drug, etoposide. This protection was accompanied
      by abrogation of etoposide-induced stimulation of caspase activity via a
      mechanism dependent on Erk and PI3K. In contrast, perturbation of cellular
      signaling mediated by the LPA(2) receptor by knockdown of a scaffold protein
      NHERF2 abrogated the protective effect of LPA. Etoposide decreased the expression
      of Bcl-2, which was reversed by LPA. Etoposide decreased the phosphorylation
      level of the proapoptotic protein Bad in an Erk-dependent manner, without
      changing Bad expression. We further show that LPA treatment resulted in delayed
      activation of Erk. These results indicate that LPA protects Caco-2 cells from
      apoptotic insult by a mechanism involving Erk, Bad, and Bcl-2.

PMID- 17544221
TI  - Prevention of self-immolation by community-based intervention.
AB  - OBJECTIVE: To describe the effectiveness of a community-based program targeting
      prevention of self-immolation. Suicide by burning is rare in developed countries
      (0.1-1.8% of all suicides), but more frequent in developing countries (up to 41%
      of all suicides). Self-immolation constitutes from 0.4% to 40% of admissions to
      burn centers worldwide. During 2001, an average of 11 Iranians committed suicide
      daily, 4 of these being self-immolations (36%). Self-immolation caused from 4% to
      28% of all admissions to Iranian burn centers. Approximately 80% of hospitalized
      self-immolation patients die. All descriptive self-immolation studies in Iran
      emphasize the need for implementing prevention programs. DESIGN: Quasi
      experimental. SETTING: The Iranian cities Gilangharb (intervention) and
      Sarpolzahab (reference). PARTICIPANTS: The populations of these communities.
      METHODS: Hospital data collection on self-immolation patients and suicide
      attempts (all mechanisms) was made from 21 March 1999 to 20 March 2003. The first
      12 months of the study provided baseline data, while the last 3 years comprised
      of a community-based intervention, using a mix of passive and active
      interventions. Videos showing victim stories were an important component in the
      prevention program. The interventions were particularly aimed at young women and
      socio-economically deprived groups, these being shown to be at high risk in
      earlier studies. RESULTS: Compared to baseline, the mean self-immolation attempts
      rate decreased by 57% after the implementation of the intervention in Gilangharb
      (p=0.04, Yates corrected p=0.07). Correspondingly, the reference city rate
      decreased 27% (n.s.). Moreover, in Gilangharb a 19% decrease of suicide attempts
      (all mechanisms) was observed while the corresponding reference city rate
      increased by 24% (n.s.). While the suicide attempt rates were similar in the two
      populations during baseline, the mean rates observed during the intervention
      period differed significantly (p<0.0001). CONCLUSIONS: A community prevention
      program targeting self-immolation can be effective. Local data and the showing of
      videos depicting victim stories from self-immolation attempts provided a stimulus
      for community action.

PMID- 17544222
TI  - Nociception increases during opioid infusion in opioid receptor triple knock-out
      mice.
AB  - Opioids are extensively used analgesics yet can paradoxically increase pain
      sensitivity in humans and rodents. This hyperalgesia is extensively
      conceptualized to be a consequence of opioid receptor activity, perhaps providing
      an adaptive response to analgesia, and to utilize N-methyl-D-aspartate (NMDA)
      receptors. These assumptions were tested here in opioid receptor triple knock-out
      (KO) mice lacking all three genes encoding opioid receptors (mu, delta, and
      kappa) by comparing their thermal nociceptive responses to the opioids morphine
      and oxymorphone with those of B6129F(1) controls. Injecting acute opioid bolus
      doses in controls caused maximal analgesia that was completely abolished in KO
      mice, confirming the functional consequence of the KO mouse opioid receptor
      deficiency. Continuous opioid infusion by osmotic pump in control mice also
      initially caused several consecutive days of analgesia that was shortly
      thereafter followed by several consecutive days of hyperalgesia. In contrast,
      continuously infusing KO mice with opioids caused no detectable analgesic
      response, but only immediate and steady declines in nociceptive thresholds
      culminating in several days of unremitting hyperalgesia. Finally, injecting the
      non-competitive NMDA receptor antagonist MK-801 during opioid infusion markedly
      reversed hyperalgesia in control but not KO mice. These data demonstrate that
      sustained morphine and oxymorphone delivery causes hyperalgesia independently of
      prior or concurrent opioid or NMDA receptor activity or opioid analgesia,
      indicating the contribution of mechanisms outside of current conceptions, and are
      inconsistent with proposals of hyperalgesia as a causative factor of opioid
      analgesic tolerance.

PMID- 17544223
TI  - Differential regulation of the expression of Period2 protein in the limbic
      forebrain and dorsomedial hypothalamus by daily limited access to highly
      palatable food in food-deprived and free-fed rats.
AB  - Circadian clock genes are rhythmically expressed in many areas of the brain and
      body and are thought to underlie most endogenous circadian behaviors and
      physiological processes. Daily rhythms of clock gene expression throughout the
      brain and body are normally coordinated by the suprachiasmatic nucleus (SCN), but
      they are also strongly influenced by daily temporal restrictions of food
      availability. Here, we studied the effects of a daily restricted presentation of
      highly palatable complete meal replacement, chocolate Ensure Plus (Ensure) in
      food-deprived (restricted feeding, RF) and free-fed (restricted treat, RT) rats,
      on the expression of the clock protein, Period2 (PER2) in regions of the brain
      involved in motivational and emotional regulation; these include the oval nucleus
      of the bed nucleus of the stria terminalis (BNSTov), the central nucleus of the
      amygdala (CEA), the basolateral amygdala (BLA), the dentate gyrus (DG) and the
      dorsomedial hypothalamus (DMH). RF and RT rats consumed similar amounts of
      Ensure, but changes in the pattern of PER2 expression were seen only in the RF
      condition, suggesting that changes in PER2 expression in these regions are
      triggered by the daily alleviation of a negative metabolic state associated with
      RF and are independent of the positive incentive properties of the consumed
      substance, per se. In contrast, the expression of the immediate early gene, Fos,
      was increased in these regions by both RF and RT schedules, showing that signals
      concerning the incentive value of the consumed food reach these regions. No
      changes in either PER2 or Fos expression were observed in the SCN of RF or RT
      rats. These findings demonstrate that mechanisms leading to changes in the
      expression of PER2 and those affecting the induction of Fos under RF and RT are,
      at least in part, dissociable.

PMID- 17544224
TI  - Neural plasticity maintained high by activation of cyclic AMP-dependent protein
      kinase: an age-independent, general mechanism in cat striate cortex.
AB  - Adult cats lack ocular dominance plasticity, showing little change in the ocular
      dominance distribution following monocular deprivation. Ocular dominance
      plasticity is also lost in kitten visual cortex that has been continuously
      infused with either catecholaminergic neurotoxin, beta-adrenoreceptor blocker, or
      inhibitor of cyclic AMP-dependent protein kinase (protein kinase A).
      Complementarily, in adult cats we showed earlier that pharmacological activation
      of protein kinase A, albeit partially, restored ocular dominance plasticity. In
      the present study, we first asked whether, mediated by protein kinase A
      activation, the same molecular mechanisms could restore ocular dominance
      plasticity to kitten cortex that once lost the expression of plasticity due to
      prior pharmacological treatments. Concurrently with monocular deprivation, two
      kinds of cyclic AMP-related drugs (cholera toxin A-subunit or dibutyryl cyclic
      AMP) were directly infused in two types of aplastic kitten cortex pretreated with
      either 6-hydroxydopamine or propranolol. The combined treatment resulted in clear
      ocular dominance shift to the non-deprived eye, indicating that cortical
      plasticity was fully restored to aplastic kitten cortex. Next, to directly prove
      the sensitivity difference in protein kinase A activation between the immature
      and mature cortex, we compared the thus-obtained data in kittens with the
      published data derived from adult cats under the comparable experimental
      paradigm. The extent of ocular dominance changes following monocular deprivation
      was compared at different drug concentrations in the two preparations: the
      shifted ocular dominance distribution in aplastic kitten cortex infused with
      dibutyryl cyclic AMP at the lowest concentration tested and the W-shaped
      distribution in similarly treated adult cortex at a thousandfold-higher drug
      concentration that induced nearly maximal changes. We conclude that, irrespective
      of the animal's age, activation of protein kinase A cascades is a general
      mechanism to maintain ocular dominance plasticity high, their sensitivity being
      substantially higher in the immature than mature cortex.

PMID- 17544225
TI  - Drug and alcohol use among the Bedouin of the Negev: prevalence and psychosocial
      correlates.
AB  - The primary aim of this study was to estimate the prevalence of drug and alcohol
      use among the Bedouin of the Negev. A representative sample of 821 adults and 440
      adolescents were surveyed using the Arabic version of the Israeli National
      Epidemiological Questionnaire. Almost 14% of adult Bedouins used alcohol and
      11.1% used illicit drugs during the past year, with rates higher among
      individuals living in government settlements than those living in unrecognized
      traditional villages. Among adolescents, 21.9% used alcohol and 20.4% used drugs
      over the past year, with rates higher for high school students than for school
      attritters. Drug use was positively associated with being male, having a tolerant
      attitude toward drug use, the perception that drugs were not dangerous, being
      secular, low family cohesion and either low or high family adaptability. These
      data suggest that drug use is prevalent among the Bedouin of the Negev,
      particularly among adolescents, who report using drugs such as narcotics,
      cocaine, and hallucinogens at rates 3 to 8 times greater than Israeli Jewish
      secular students. School-based and family-based prevention and treatment programs
      may be most effective for this population.

PMID- 17544226
TI  - The effects of cigarette smoking on script-driven imagery in smokers with and
      without posttraumatic stress disorder.
AB  - The study investigated the effects of smoking a nicotinized or denicotinized
      cigarette on craving, affect and posttraumatic stress disorder (PTSD) symptoms
      while recalling neutral, stressful and traumatic events in smokers with and
      without PTSD. Smokers completed laboratory sessions during which they were
      presented with audiotapes of personalized scripts followed by smoking a
      cigarette. The effect of the script and cigarette conditions on dependent
      variables was evaluated. There was a main effect of script type across groups for
      smoking craving, negative affect and PTSD symptoms, with increased symptoms in
      trauma and stressful conditions. Responses were significantly higher in PTSD
      smokers. Smoking either cigarette type resulted in decreased craving, negative
      affect and PTSD symptoms in both groups. A second script presentation following
      smoking elicited similar responses, suggesting the ameliorative effect of having
      smoked a cigarette was short-lived. These results support that context and non
      pharmacologic effects of smoking are important variables in smoking craving and
      mood, particularly in smokers with PTSD.

PMID- 17544227
TI  - Non-medical use, abuse and dependence on sedatives and tranquilizers among U.S.
      adults: psychiatric and socio-demographic correlates.
AB  - BACKGROUND: Non-medical use of sedatives and tranquilizers carries risks
      including development of abuse/dependence. Such use may correlate with
      psychiatric symptoms. METHODS: Cross-sectional survey, the 2002-2004 National
      Survey on Drug Use and Health. Respondents 18 years and older (n=92,020).
      Bivariate and multivariable associations were investigated. RESULTS: The
      prevalence of past-year non-medical use of sedatives or tranquilizers was 2.3%.
      Of those with non-medical use, 9.8% met criteria for abuse/dependence. On
      multivariable analysis, panic symptoms and elevated serious mental illness scores
      were associated with past-year non-medical use. Also, the following past-year
      socio-demographic and substance use covariates were associated with past-year non
      medical sedative or tranquilizer use: female sex, white/hispanic/other ethnicity,
      criminal arrest, uninsurance, unemployment, alcohol abuse or dependence,
      cigarette use, illicit drug use, younger age of initiating illicit substance use,
      and any history of IV drug use. Among those with sedative or tranquilizer use,
      those with abuse/dependence were more likely to have agoraphobic symptoms. In
      addition, they were more likely to be older, unmarried, have a low education
      level and have been arrested. CONCLUSIONS: Non-medical use of sedatives and
      tranquilizers is common. Furthermore, nearly 10% of those with non-medical use
      meet criteria for abuse/dependence. Anxiety symptoms associated with non-medical
      use (panic symptoms) and abuse/dependence (agoraphobia) should alert clinicians
      to screen for these problems and consider alternate treatment or referral.

PMID- 17544229
TI  - Chromosomal position, structure, expression, and requirement of genes for chicken
      transcription factor IIA.
AB  - Transcription factor IIA (TFIIA) is one of the general transcription factors for
      RNA polymerase II and composed of three subunits, TFIIAalpha, TFIIAbeta and
      TFIIAgamma. TFIIAalpha and TFIIAbeta are encoded by a single gene
      (TFIIAalphabeta) and mature through internal cleavage of TFIIAalphabeta. In this
      study, we found that structures of TFIIAalphabeta and TFIIAgamma are highly
      homologous with each mammalian counterpart. Exon-intron organizations of the
      human and chicken TFIIA genes were also homologous. The sequence of the cleavage
      region of the chicken TFIIAalphabeta precursor protein was fitted to the
      consensus cleavage recognition site. It was thus demonstrated that TFIIA is
      conserved in vertebrates. TFIIA proteins are present ubiquitously in chicken
      tissues. Fluorescent in situ hybridization revealed that TFIIAalphabeta and
      TFIIAgamma genes are located in chromosome 5 and a mini-chromosome, respectively.
      We generated semi-knockout chicken DT40 cells for TFIIAalphabeta and TFIIAgamma
      genes with high homologous recombination efficiencies, whereas we failed to
      establish double-knockout cells for each gene. It is thought that both genes for
      TFIIA are required in vertebrates. TFIIA siRNA resulted in deceleration of cell
      growth rate, suggesting that, consistent with those of knockout assays, TFIIA is
      associated with cell growth regulation.

PMID- 17544228
TI  - Remodeling of chromatin structure in senescent cells and its potential impact on
      tumor suppression and aging.
AB  - Cellular senescence is an important tumor suppression process, and a possible
      contributor to tissue aging. Senescence is accompanied by extensive changes in
      chromatin structure. In particular, many senescent cells accumulate specialized
      domains of facultative heterochromatin, called Senescence-Associated
      Heterochromatin Foci (SAHF), which are thought to repress expression of
      proliferation-promoting genes, thereby contributing to senescence-associated
      proliferation arrest. This article reviews our current understanding of the
      structure, assembly and function of these SAHF at a cellular level. The possible
      contribution of SAHF to tumor suppression and tissue aging is also critically
      discussed.

PMID- 17544230
TI  - Trithorax-group protein ASH1 methylates histone H3 lysine 36.
AB  - Drosophila discs absent, small, or homeotic-1 (ASH1) is a member of trithorax
      group proteins that play essential roles in epigenetic regulation of Hox genes.
      Drosophila ASH1 genetically interacts with trithorax and has been reported to
      methylate histone H3 lysine 4 (K4) as well as H3 K9 and H4 K20. The function of
      mammalian ASH1, by contrast, has remained largely unknown. Here we report a
      histone lysine scanning mutation assay using recombinant core histones and in
      vitro reconstituted nucleosomes to identify targets of mammalian
      methyltransferases by fluorographic, Western blot, and mass spectrometric
      analyses. The assay reproduced specificities of previously known histone
      methyltransferases and further revealed unexpectedly that mammalian ASH1 mono- or
      di-methylates histone H3 K36 but not any other lysine residues of recombinant
      unmodified mammalian histones. Under the same experimental condition, lysine to
      arginine substitution of histone H3 at position 36 abolished the
      methyltransferase activity of Drosophila ASH1, suggesting that K36 is their
      specific target. We also demonstrate that native ASH1 proteins, consisting of the
      carboxy-terminal domains including the catalytic site, retain the specificity for
      K36. Taken together, our data suggest that ASH1 subfamily of SET domain proteins
      have K36-specific methyltransferase activities evolutionarily conserved from
      flies to mammals.

PMID- 17544231
TI  - Identification and differentiation of canine Mycoplasma isolates by 16S-23S rDNA
      PCR-RFLP.
AB  - Conventional serological methods for the identification of canine mycoplasma
      isolates depend on the availability of a panel of species-specific diagnostic
      antisera and are not always reliable in terms of specificity. To enable
      simultaneous identification of field isolates, PCR-RFLP analysis of the 16S-23S
      rRNA intergenic spacer region was used to characterize the type strains of the 12
      currently described canine mycoplasmas of the Genus Mycoplasma which represent
      the "classic" non-hemotropic species. The use of 16S-23S rDNA PCR in the first
      step of this analysis revealed specific size differences of amplicons which
      allowed to classify these 12 canine Mycoplasma species into three groups.
      Depending on the length of the amplicon, subsequent RFLP analysis of PCR products
      using two restriction endonucleases in a single digest (ApoI/DdeI or TaqI/VspI)
      generated unique banding patterns. For further evaluation of the 16S-23S rDNA PCR
      RFLP assay system as identification and differentiation tool, a total of 262
      field isolates collected from the canine genital tract were tested. PCR-RFLP
      results for 251 field isolates correlated with traditional serological test
      results. The remaining 11 isolates had an RFLP pattern distinct from the type
      strains included in this study and were identified by 16S rDNA sequencing as
      closely related to M. sp. HRC689. The PCR-RFLP assay established in this study
      enabled a rapid, accurate and easily performed identification and differentiation
      of all 12 currently described non-hemotropic canine Mycoplasma species.

PMID- 17544232
TI  - Isolation of surface (S) layer protein carrying Lactobacillus species from
      porcine intestine and faeces and characterization of their adhesion properties to
      different host tissues.
AB  - Surface-layer proteins (Slps) of lactobacilli have been shown to confer tissue
      adherence. This study aimed to isolate and identify Slps carrying Lactobacillus
      species from the porcine intestine and faeces and to characterize these S-layer
      expressing strains for their ability to adhere to the pig and human intestinal
      cells and to extracellular matrix (ECM) proteins. In total 99 strains, putatively
      belonging to the genus Lactobacillus, were isolated as pure cultures. SDS-PAGE
      and a gene probe specific for the Lactobacillus brevis ATCC 8287 S-layer protein
      gene (slpA) were used to screen the presence of strains possessing putative Slps.
      Eight of the 99 pure cultures exhibited Slps according to the SDS-PAGE analyses.
      In these strains the presence of genes encoding Slps was confirmed by PCR and
      partial sequencing. Only one isolate of the 99 strains gave a positive
      hybridisation signal with the L. brevis slpA probe but did not appear to produce
      S-layer protein. Their taxonomic identification, based on phenotyping and the 16S
      rRNA sequences, revealed that the eight S-layer protein-producing strains were
      closely related to Lactobacillus amylovorus, Lactobacillus sobrius and
      Lactobacillus crispatus. The strain with the slpA positive hybridisation result
      was identified as Lactobacillus mucosae. The SDS-extractable protein profile, the
      size of the putative S-layer protein and binding capability of the strains varied
      greatly, even among the isolates belonging to the same Lactobacillus cluster.
      Removal of the intact Slps from the bacterial surface by extraction with
      guanidine hydrochloride reduced the adhesion of some strains to fibronectin and
      laminin, whereas, the adhesiveness to laminin increased with some strains.

PMID- 17544233
TI  - Identification and characterization of transcriptional regulation of the
      Mannheimia haemolytica ferric uptake regulator.
AB  - The ferric uptake regulator (Fur) is an iron-dependent transcriptional regulator
      that regulates genes related to iron acquisition, oxidative stress response, and
      various other functions. Transcription of fur is typically self-regulating and
      sensitive to iron and oxidative stress. Following the identification of a fur
      gene in the genome of the bovine pathogen Mannheimia haemolytica, an attempt was
      made to characterize the transcriptional control of M. haemolytica fur. Northern
      blotting, RT-PCR, and primer extension were done to determine that M. haemolytica
      fur is transcribed using three distinct promoters, two of which are located
      within the upstream fldA gene. The third promoter is located upstream of a
      conserved hypothetical protein and drives transcription of a tricistronic
      message. Quantitative real time PCR experiments indicated that unlike current
      models of Fur regulation, M. haemolytica fur transcription is unchanged by iron
      depletion at logarithmic phase and repressed by iron depletion at stationary
      phase.

PMID- 17544234
TI  - Phenotypic and genotypic antimicrobial resistance patterns of Escherichia coli
      isolated from dairy cows with mastitis.
AB  - Pulsed field gel electrophoresis (PFGE) patterns, susceptibility to 26
      antimicrobial agents used in veterinary and human medicine, and prevalence of
      antimicrobial resistance genes of Escherichia coli isolated from cows with
      mastitis were evaluated. Among 135 E. coli isolates, PFGE analysis revealed 85
      different genetic patterns. All E. coli were resistant to two or more
      antimicrobials in different combinations. Most E. coli were resistant to
      antimicrobials used in veterinary medicine including ampicillin (98.4%, >or=32
      microg/ml) and many E. coli were resistant to streptomycin (40.3%, >or=64
      microg/ml), sulfisoxazole (34.1%, >or=512 microg/ml), and tetracycline (24.8%,
      >or=16 microg/ml). Most E. coli were resistant to antimicrobials used in human
      medicine including aztreonam (97.7%, >or=32 microg/ml) and cefaclor (89.9%,
      >or=32 microg/ml). Some E. coli were resistant to nitrofurantoin (38%, >or=128
      microg/ml), cefuroxime (22.5%, >or=32 microg/ml), fosfomycin (17.8%, >or=256
      microg/ml). All E. coli were susceptible to ciprofloxacin and cinoxacin. Almost
      97% (123 of 127) of ampicillin-resistant isolates carried ampC. Eleven of 52
      (21.2%) streptomycin-resistant isolates carried strA, strB and aadA together and
      29 streptomycin-resistant isolates (55.8%) carried aadA alone. Among 44
      sulfisoxazole-resistant E. coli, 1 isolate (2.3%) carried both sulI and sulII, 12
      (27.3%) carried sulI and 10 (22.7%) isolates carried sulII. Among 32 tetracycline
      resistant isolates, 14 (43.8%) carried both tetA and tetC and 14 (43.8%) carried
      tetC. Results of this study demonstrated that E. coli from cows with mastitis
      were genotypically different, multidrug resistant and carried multiple resistance
      genes. These bacteria can be a reservoir for antimicrobial resistance genes and
      can play a role in the dissemination of antimicrobial resistance genes to other
      pathogenic and commensal bacteria in the dairy farm environment.

PMID- 17544235
TI  - An evolutionary perspective on the origin and ontogeny of menopause.
AB  - The "grandmother hypothesis" proposes that menopause evolved because ancestral
      middle-aged women gained greater reproductive success from investing in extant
      genetic relatives than from continuing to reproduce [Williams GC. Pleiotropy,
      natural selection, and the evolution of senescence. Evolution 1957;11:398-411].
      Because middle-aged women faced greater risks of maternal death during pregnancy
      and their offspring's infancy than did younger women, offspring of middle-aged
      women may not have received the needed level of prolonged maternal investment to
      survive to reproductive age. I put forward the "absent father hypothesis"
      proposing that reduced paternal investment linked with increasing maternal age
      was an additional impetus for the evolution of menopause. Reduced paternal
      investment was linked with increasing maternal age because men died at a younger
      age than their mates and because some men were increasingly likely to defect from
      their mateships as their mates aged. The absent father hypothesis is not an
      alternative to the grandmother hypothesis but rather a complement. It outlines an
      additional cost--reduced paternal investment--associated with continued
      reproduction by ancestral middle-aged women that could have been an additional
      impetus for the evolution of menopause. After reviewing additional explanations
      for the origin of menopause ("patriarch hypothesis," "lifespan-artifact"
      hypotheses), I close by proposing a novel hypothesis for the ontogeny of
      menopause. According to the "adaptive onset hypothesis," the developmental timing
      of menopause is a conditional reproductive strategy in which a woman's age at
      onset is influenced by the likelihood that any children she could produce would
      survive to reproductive age. Twelve variables predicted to be associated with age
      at onset and evidence that bears upon the predictions is discussed.

PMID- 17544236
TI  - Neonatal death following clozapine self-poisoning in late pregnancy: an unusual
      case report.
AB  - The report presents a fatal poisoning of a neonate occurring in the final stage
      of gestational life and evoked by his mother, who, while 9 months pregnant, took
      a toxic dose of clozapine aiming at committing suicide. She was also severely
      poisoned, but ultimately was saved. The woman had been taking the medication due
      to schizophrenia and depression prior to conception, and the discontinuation of
      the drug in the course of pregnancy increased the risk of the woman attempting
      suicide. In the course of comprehensive toxicological analysis based on the
      developed analytical procedure with the use of LC-APCI-MS, clozapine and its two
      metabolites, norclozapine and clozapine-N-oxide, were determined in postmortem
      blood, liver and kidney in concentrations explaining the death of the neonate.
      The interpretation of the above-described case is complex and--apart from
      toxicological aspects--also involves issues associated with psychiatry,
      pharmacotherapy in pregnancy and medicolegal problems.

PMID- 17544237
TI  - Life-threatening hobbies in the youth? Two autoptic cases suggesting
      arrhythmogenic right ventricular cardiomyopathy.
AB  - Determining the cause for the sudden death in young adults tends to be complex
      and difficult. Two cases of death of young people were autoptically investigated
      who died suddenly while carrying out their hobbies (a 22-year-old male musician
      and a 20-year-old female dancer). In both cases neither the police investigation,
      the autopsy, nor the toxicological investigations gave any relevant results.
      However, when investigating the histology fatty and fibrotic tissue in the right
      ventricle of the myocardium were found, whereas the myocytes proved to be
      degenerated--typical for arrhythmogenic right ventricular cardiomyopathy (ARVC).
      It is important to consider the possibility of heart rhythm failure if a clear
      reason for sudden death in young adults cannot be detected. Heart rhythm failure
      often involves the genetic background of the case, which suggests that genetic
      analysis should be carried out as a supportive means of diagnostics.

PMID- 17544238
TI  - Identification of menstrual blood by real time RT-PCR: technical improvements and
      the practical value of negative test results.
AB  - The identification of body fluids can be of crucial importance in forensic
      casework. Recently we have shown that the detection of cell- and tissue-specific
      mRNAs is a suitable technique to identify menstrual blood and semen. In this
      paper we present an improved method using real time-PCR and the menstrual blood
      marker MMP-7 which increases sensitivity and specificity. We furthermore
      demonstrate case examples described showing that the correct identification of
      samples as non-menstrual is likely to be in the focus of criminal investigations.
      Although negative test results may have a number of other reasons, the new
      technique provides quantitative results thus allowing a cut-off value for the
      control marker GAPDH to be defined, below which negative results for the
      menstrual blood marker MMP-7 allow the conclusion that the sample was indeed not
      menstrual blood. Using these data, it is possible to apply the molecular
      identification of menstrual blood to forensic casework considering both the
      limitations and the capabilities of the method.

PMID- 17544239
TI  - Older people's preferences for involvement in their own care: a qualitative study
      in primary health care in 11 European countries.
AB  - OBJECTIVE: The aim of the study was to explore the views of people aged over 70
      years on involvement in their primary health care in 11 different European
      countries. METHODS: Older patients were asked about their views on patient
      involvement in a face-to-face interview. All interviews were audio-recorded,
      transcribed and analysed in accordance with the principles of 'qualitative
      content analysis'. An international code list was used. RESULTS: Four hundred and
      six primary care patients aged between 70 and 96 years were interviewed. Their
      views could be categorized into four major groups: doctor-patient interaction, GP
      related topics, patient related issues and contextual factors. CONCLUSION: People
      over 70 do want to be involved in their care but their definition of involvement
      is more focussed on the 'caring relationship', 'person-centred approach' and
      'receiving information' than on 'active participation in decision making'.
      PRACTICE IMPLICATIONS: The desire for involvement in decision making is highly
      heterogeneous so an individual approach for each patient in the ageing population
      is needed. Future research and medical education should focus on methods and
      training to elicit older patients' preferences. The similar views in 11 countries
      suggest that methods for enhancing patient involvement in older people could be
      internationally developed and exchanged.

PMID- 17544240
TI  - Expression and mutation analysis of Tpit in the canine pituitary gland and
      corticotroph adenomas.
AB  - Pituitary-dependent hyperadrenocorticism (PDH) in dogs is caused by a pituitary
      corticotroph adenoma. Although PDH is a common disorder in dogs, little is known
      about the underlying pathogenesis. In the pituitary glands of humans and mice,
      the pro-opiomelanocortin (POMC)-expressing cell lineages, the corticotrophs and
      melanotrophs, have a specific marker in common, the T-box transcription factor
      Tpit (Tbx19), which is obligate for POMC expression. Tpit also regulates the late
      differentiation of the corticotrophs and melanotrophs, and therefore may
      contribute to the pathogenesis of the corticotroph adenomas. The aim of this
      study was to perform an expression and mutation analysis of Tpit in the normal
      canine pituitary and in corticotroph adenomas. The distribution of the Tpit
      protein in the pituitary gland was studied with immunohistochemistry and the
      expression of the gene with RT-PCR. The coding region of Tpit cDNA from 14 dogs
      with PDH was screened for mutations. Tpit was expressed in corticotroph and
      melanotroph cells of the normal and adenomatous canine pituitary, and remained
      present in non-adenomatous corticotrophs of pituitaries from PDH dogs. No tumor
      specific mutation in the Tpit cDNA from the corticotroph adenomas was found.
      However, a missense polymorphism in the highly conserved DNA-binding domain, the
      T-box, was discovered in one dog. It is concluded that Tpit can be used as a
      reliable marker for the corticotroph and melanotroph cells in the canine
      pituitary tissue and that mutations in the Tpit gene are unlikely to play a major
      role in the pathogenesis of canine corticotroph adenomas.

PMID- 17544241
TI  - [Actualities in paediatric anaesthesia and critical care medicine].

PMID- 17544242
TI  - Cognitive impairment in patients with neuropathic pain.

PMID- 17544243
TI  - Report of the clinical protocol committee: development of randomized trials for
      malignant bowel obstruction.
AB  - Malignant bowel obstruction (MBO) is a commonly encountered palliative care
      problem. There have been very few comparative trials in this area, and
      consequently there is very little clinical evidence upon which therapy can be
      rationally based. The purpose of this paper is to highlight the discussion and
      decision-making process that was undertaken by the Clinical Protocol Subcommittee
      during the development of a proposed clinical trial of best medical care versus
      surgical or endoscopic treatment for MBO. The development of the proposed
      clinical trials followed an orderly process. The first step taken was a
      discussion of a specific definition for MBO. Once agreed upon, this definition
      helped identify inclusion and exclusion criteria for the proposed trial. This was
      followed by an extensive literature review, which helped define both surgical and
      endoscopic approaches to MBO as well as what constituted best medical care. An
      extensive discussion was then undertaken concerning the best outcome measure of
      success for medical, surgical, and endoscopic interventions. All of the above
      steps culminated in two proposed protocols, one for MBO of the small intestine
      distal to the ligament of Treitz and a second for colonic obstructions. The small
      intestinal trial is designed to compare surgical intervention versus best medical
      care, whereas the colonic trial seeks to compare surgery with endoscopically
      placed intraluminal stents coupled with best medical care.

PMID- 17544244
TI  - Coping with recurrent breast cancer: predictors of distressing symptoms and
      health-related quality of life.
AB  - Little is known about how postmenopausal women with recurrent breast cancer cope
      with distressing symptoms and which factors predict health-related quality of
      life (HRQOL). In the present study, 56 consecutively enrolled patients completed
      questionnaires measuring symptom occurrence, coping capacity, coping efforts, and
      HRQOL at the time of recurrence. Results from this study illustrate that women
      with recurrent breast cancer suffer from multiple, concurrent, and interrelated
      symptoms of illness, anxiety, depression, and fatigue. Highly prevalent symptoms
      are lack of energy, difficulty sleeping, pain, worrying, problems with sexual
      interest, feeling sad, and dry mouth. The most frequently occurring symptom is
      problem with sexual interest, and the most severe symptom is worrying. The most
      distressing symptom experienced is pain. The majority of the women report 10-23
      symptoms. Women who experience multiple symptoms also report higher levels of
      symptom distress. The experience of distressing symptoms is predicted by coping
      capacity, and the coping efforts experienced predict HRQOL. Patients with lower
      coping capacity report higher prevalence of symptoms, experience higher levels of
      distress, and experience worse perceived health, which in turn may decrease their
      HRQOL. To help women manage recurrent breast cancer, it is important to use
      multidimensional measurement to identify, evaluate, and treat distressing
      symptoms, and not assess single symptoms only. Care must be based upon the
      awareness of critical factors that exacerbate vulnerability to distress, as well
      as the ability to adapt to a recurrent breast cancer disease.

PMID- 17544245
TI  - Implementing palliative care studies.
AB  - This session focused on issues related to implementation of randomized clinical
      trials in palliative care studies. Topics discussed included what kinds of
      clinical sites and patient populations were suitable, what types of clinical
      investigators (clinical specialty) should be involved in or lead the studies,
      what multisite mechanisms could be used to conduct the trials, and what funding
      issues were related to these studies. A trial of operative versus nonoperative
      management for small bowel obstruction caused by recurrent intra-abdominal cancer
      was considered. The feasibility of such a trial was examined in terms of whether
      there was "equipoise" for a majority of likely investigators in the field around
      the trial question, what other issues might impact accrual to the trial, and how
      many patients would be required to answer which of these two treatment arms was
      better. This last question is related to selection of a primary endpoint for the
      trial and was a modestly contentious issue for the trial design group. Both
      sensible compromises in endpoint selection and the education of the community of
      investigators for a particular randomized trial in palliative care are crucial
      steps for successful implementation. A major conclusion of this session is that
      implementation considerations are intimately related to the architecture of a
      specific trial and should be addressed practically and early in the design phase
      of any randomized trial addressing a palliative care question. In this respect,
      randomized trials in palliative care are no different than in other fields.

PMID- 17544246
TI  - The experience of cancer-related fatigue and chronic fatigue syndrome: a
      qualitative and comparative study.
AB  - Cancer-related fatigue (CRF) is a common and disabling symptom complex reported
      by survivors. This study aimed to better understand the manifestations of CRF in
      women treated for breast cancer, and to compare them with those of women
      diagnosed with chronic fatigue syndrome (CFS). Women with CRF persisting 6 months
      after treatment for early stage breast cancer, and women with CFS participated in
      separate, audiotaped focus groups. Transcripts of the sessions were analyzed
      using the NUD*IST software, and interpreted using grounded theory. Twenty-eight
      women participated, 16 with CRF and 12 with CFS. Analysis of transcripts from
      both groups revealed a similar core set of symptoms, featuring fatigue,
      neurocognitive difficulties, and mood disturbances. Women with CFS reported
      additional symptoms including musculoskeletal pain and influenza-like
      manifestations. Both groups suffered disabling behavioral consequences of the
      symptom complex. Qualitatively, CRF appears closely related to CFS. These
      findings raise the emergent hypothesis of a conserved neurobehavioral symptom
      complex, which results from diverse triggering insults.

PMID- 17544247
TI  - Discrepant perceptions about end-of-life communication: a systematic review.
AB  - Little research has compared the perceptions of health professionals (HPs),
      patients, and caregivers about the communication of prognostic information. The
      objectives of this literature review were to determine 1) patient and caregiver
      perceptions of levels of information received about prognosis and end-of-life
      (EoL) issues regarding a life-limiting illness; 2) patient perceptions of and
      factors related to their understanding and awareness of prognosis; 3) HPs'
      perceptions of patients' wishes about disclosure of prognosis and factors related
      to their decision whether to disclose; and 4) concordance between HPs and
      patients/caregivers regarding the information given by HPs about prognostic and
      EoL issues. Relevant studies meeting the inclusion criteria were identified by
      searching computerized databases (MEDLINE, EMBASE, CINAHL, PsychINFO, Cochrane
      Register of Controlled Trials [Central]) up to November 2004. The reference lists
      of identified studies were hand searched for further relevant studies. Inclusion
      criteria were studies of any design evaluating communication of prognostic
      information that included adult patients with an advanced, life-limiting illness;
      their caregivers; and qualified HPs. Fifty-one studies were identified. There was
      a large discrepancy between patients/caregivers and HPs regarding the amount of
      information they believed had been given. Patients' understanding and awareness
      of information received conflicted with the HPs' perceptions of patients'
      understanding and awareness of the information that had been given. HPs tended to
      underestimate patients' need for information and overestimate patients'
      understanding and awareness of their prognosis and EoL issues. HPs need to
      repeatedly check patients' understanding and preferences for information.

PMID- 17544248
TI  - Lessons learned from a collaborative meeting to construct a palliative care
      protocol.
AB  - As the treatment of advanced illness necessitates a multidimensional and
      culturally sensitive approach, a conference of international leaders in affected
      disciplines (quality of life research, ethno-cultural variability, palliative
      medicine, surgical oncology, gastroenterology, major consortium research, medical
      ethics, and patient advocacy/cancer survivors) was organized to provide the
      necessary expertise and broad ethnic and racial perspectives. During the course
      of the two-day conference, participants first deliberated in small groups focused
      on specific areas of concern to palliative care research: outcome measures,
      ethical dilemmas, barriers, and solutions, cross-cultural issues, palliative care
      study implementation, and protocol development. Each group presented the results
      of their meetings, and the conference as a whole worked out the final details of
      a research protocol for malignant bowel obstruction. Lessons learned in the
      process of conceiving and organizing the meetings, implementing, and
      disseminating the results of the conference provide insight into the usefulness
      of this method for developing workable palliative care research methodologies.

PMID- 17544249
TI  - A retrospective chart review of the antiemetic effectiveness of risperidone in
      refractory opioid-induced nausea and vomiting in advanced cancer patients.
AB  - Nausea and vomiting are distressing symptoms in advanced cancer patients. The
      causes of nausea and vomiting are multifactorial. Among the causes is opioid
      therapy, the mainstay of cancer pain management. When nausea or other opioid side
      effects occur, it may hamper pain management and undermine the quality of life of
      cancer patients. Risperidone exerts an antiemetic effect in animals, but there
      has been no clinical report on its antiemetic activity. We conducted a
      retrospective chart review to examine whether risperidone is useful for opioid
      induced nausea and vomiting in advanced cancer patients (n=20). Risperidone was
      given as doses of 1mg once a day. Complete response was observed in 50% of
      patients (10/20) for nausea and 64% (7/11) for vomiting. Sedation (n=2) was
      documented as an adverse effect. This observation suggests that risperidone can
      be an effective antiemetic drug in the treatment of refractory opioid-induced
      nausea and vomiting in advanced cancer patients.

PMID- 17544250
TI  - Meaninglessness in terminally ill cancer patients: a validation study and nurse
      education intervention trial.
AB  - Recent empirical studies revealed that fostering patients' perception of meaning
      in their life is an essential task for palliative care clinicians. However, few
      studies have reported the effects of training programs for nurses specifically
      aimed at improving skills to relieve the meaninglessness of terminally ill cancer
      patients, and we have had no specific measurement instruments. The primary aims
      of this study were 1) to validate measurement tools to quantify nurses' self
      reported practice and attitudes toward caring for terminally ill cancer patients
      feeling meaninglessness and 2) to explore the effects of the five-hour
      educational workshop focusing on meaninglessness on nurses' self-reported
      practice, attitudes toward caring for such patients, confidence, burnout, death
      anxiety, and meaning of life. A quasi-experimental pre-post questionnaire survey
      was performed on 147 nurses. The questionnaire was distributed before the
      intervention workshop and one and six months after. The workshop consisted of
      lecture, role-play, and the exercise of assessment and care planning based on two
      vignette verbatim records. First, using the first questionnaire sample and an
      additional sample of 20 nurses for the test-retest examination, we validated a
      six-item Self-Reported Practice scale, and an eight-item Attitudes Toward Caring
      for Patients Feeling Meaninglessness scale with three subscales (Willingness to
      Help, Positive Appraisal, and Helplessness). The nurses also completed a scale to
      assess confidence in caring for terminally ill patients with meaninglessness, the
      Maslach Burnout Inventory, the Death Attitude Inventory, the Frommelt Attitudes
      Toward Care of the Dying scale, the Self-Reported Practice Score in General
      Communication, and the three pain-related items from the Palliative Care Quiz for
      Nursing. For the Self-Reported Practice scale and the subscales of the Attitudes
      Toward Caring for Patients Feeling Meaninglessness scale, the Cronbach's alpha
      coefficients were 0.63-0.91, and the intra-class correlations were 0.89-0.94. The
      Self-Reported Practice scale significantly, but moderately, correlated with the
      Self-Reported Practice Score in General Communication (P=0.41). The Willingness
      to Help and Helplessness subscales significantly but weakly correlated with the
      Frommelt scale (P=-0.27, 0.21). Both scales did not correlate or minimally
      correlated with the Palliative Care Quiz for Nursing (P<0.20). The construct
      validity was confirmed using factor analysis. At the follow-up, of 147 nurses who
      participated in this workshop, 91 (62%) and 80 (54%) nurses responded. Self
      reported practice and confidence significantly improved, whereas helplessness,
      emotional exhaustion, and death anxiety significantly decreased. The percentages
      of nurses who evaluated this program as "useful" or "very useful" were 79% (to
      understand the conceptual framework in caring for terminally ill patients with
      meaninglessness), 73% (to help in self-disclosing nurses' personal beliefs,
      values, and life goals), and 80% (to help in learning how to provide care for
      patients with meaninglessness). The Self-Reported Practice scale and the
      Attitudes Toward Caring for Patients Feeling Meaninglessness scale are reliable
      and valid tools to specifically quantify nurses' self-reported practice and
      attitudes toward caring for terminally ill cancer patients feeling
      meaninglessness of life. The five-hour workshop appeared to have a modest but
      significant beneficial effect on nurse-reported practice, attitudes, and
      confidence in providing care for terminally ill cancer patients feeling
      meaninglessness. Further educational intervention trials with control groups are
      promising.

PMID- 17544251
TI  - The international conference on malignant bowel obstruction: a meeting of the
      minds to advance palliative care research.
AB  - There is a dearth of well-designed clinical research focusing on palliative care
      in cancer patients, especially those who are near the end of life. Reasons for
      this include ethical dilemmas in conducting such trials, communication barriers
      between specialties, and unclear standards for best care practices. To ensure
      that patients with incurable illnesses are offered the best available care, it is
      essential to develop and disseminate research methodologies well suited to this
      population. Given the multidimensional and culture-dependent nature of the end-of
      life experience, it is necessary to adopt an interdisciplinary approach to
      developing research methods. As a means of initiating the process of palliative
      clinical research methodology development, malignant bowel obstruction (MBO) was
      used as a model to develop a research protocol. Although many treatment options
      for MBO have been proposed, existing literature offers little guidance with
      regard to algorithms for optimal management. To this end, an international
      leaders in quality-of-life research, ethnocultural variability, palliative
      medicine, surgical oncology, gastroenterology, major consortium research, medical
      ethics, and patient advocacy/cancer survivors was convened in Pasadena,
      California, on November 12-13, 2004. Participants also represented the broad
      ethnic and racial perspectives required to develop culturally sensitive research
      methods. Consensus on methodological approaches was attained through vigorous
      debate. Using the conference-developed MBO model to implement trials will advance
      palliative care research.

PMID- 17544252
TI  - Virtual reality exposure therapy for anxiety disorders: A meta-analysis.
AB  - There is now a substantial literature investigating virtual reality exposure
      therapy (VRET) as a viable treatment option for anxiety disorders. In this meta
      analysis we provide effect size estimates for virtual reality treatment in
      comparison to in vivo exposure and control conditions (waitlist, attention
      control, etc.). A comprehensive search of the literature identified 13 studies
      (n=397) that were included in the final analyses. Consistent with prediction the
      primary random effects analysis showed a large mean effect size for VRET compared
      to control conditions, Cohen's d=1.11 (S.E.=0.15, 95% CI: 0.82-1.39). This
      finding was consistent across secondary outcome categories as well (domain
      specific, general subjective distress, cognition, behavior, and
      psychophysiology). Also as expected in vivo treatment was not significantly more
      effective than VRET. In fact, there was a small effect size favoring VRET over in
      vivo conditions, Cohen's d=0.35 (S.E.=0.15, 95% CI: 0.05-0.65). There was a trend
      for a dose-response relationship with more VRET sessions showing larger effects
      (p=0.06). Outcome was not related to publication year or sample size.
      Implications are discussed.

PMID- 17544253
TI  - The Cognitive Avoidance Questionnaire: validation of the English translation.
AB  - This study investigated the psychometric properties of the Cognitive Avoidance
      Questionnaire (CAQ; Gosselin, P., Langlois, F., Freeston, M. H., Ladouceur, R.,
      Dugas, M. J., & Pelletier, O. (2002). Le Questionnaire d'evitement cognitif
      (QEC): Developpement et validation aupres d'adultes et d'adolescents [The
      Cognitive Avoidance Questionnaire (CAQ): Development and validation among adult
      and adolescent samples]. Journal de Therapie Comportementale et Cognitive, 12, 24
      37) English translation. Questionnaires were administered to a sample of 456
      (65.3% female; mean age=23.13 years, S.D.=5.18 years) undergraduate students at
      Concordia University in Montreal, Canada. The CAQ assesses five worry-related
      cognitive avoidance strategies, namely Thought Suppression, Thought Substitution,
      Distraction, Avoidance of Threatening Stimuli, and the Transformation of Images
      into Thoughts. The CAQ scale and subscales showed good to excellent internal
      consistency and good stability over a 5-week period. A confirmatory factor
      analysis found support for the proposed subscales, though the overall goodness-of
      fit was lower than expected. Preliminary evidence of convergent and divergent
      validity was found with measures of worry, thought suppression, and dispositional
      coping styles. The relationship between the CAQ and specific dispositional coping
      styles, however, was dependent on the context of the situation in which the
      information-seeking and information-avoidant coping strategies were employed.
      Specifically, the CAQ was negatively correlated with vigilance in controllable
      situations and positively correlated with both information-avoidance in
      controllable situations and information-seeking in uncontrollable situations.

PMID- 17544254
TI  - Gene conversion between mammalian CCR2 and CCR5 chemokine receptor genes: a
      potential mechanism for receptor dimerization.
AB  - The chemokine receptor genes of the CCR cluster on human chromosome 3p21 play
      important roles in humoral and cellular immune responses. Several of these
      receptors have been shown to influence human immunodeficiency virus infection and
      progression to AIDS, and their homologues may play a role in feline
      immunodeficiency virus infection. We report the isolation and sequencing of a 150
      kb domestic cat BAC clone containing the feline CCR genes CCR1, CCR2, CCR3, and
      CCR5 to further analyze these four receptor genes within the family Felidae.
      Comparative and phylogenetic analyses reveal evidence for historic gene
      conversion between the adjacent CCR2 and CCR5 genes in the Felidae and in three
      independent mammalian orders (Primates, Cetartiodactyla, and Rodentia), resulting
      in higher than expected levels of sequence similarity between the two paralogous
      genes within each order. The gene conversion was restricted to the structural
      (transmembrane) domains of the CCR2 and CCR5 genes. We also discovered a recent
      gene conversion event between the third extracellular loop of CCR2 and CCR5 genes
      that was fixed in Asian lions and found at low frequency in African lions
      (Panthera leo), suggesting that this domain may have an important functional
      role. Our results suggest that ongoing parallel gene conversion between CCR2 and
      CCR5 promotes receptor heterodimerization in independent evolutionary lineages
      and offers an effective adaptive strategy for gene editing and coevolution among
      interactive immune response genes in mammals.

PMID- 17544255
TI  - Longitudinal analysis of pro- and anti-inflammatory cytokine production in
      severely fatigued adolescents.
AB  - In the adolescent population, fatigue is associated with somatic complaints,
      unrefreshing sleep, cognitive disturbances and symptoms of depression and
      anxiety. This pattern of symptoms resembles the one described in chronic fatigue
      syndrome (CFS). Since immunological alterations have been reported in CFS
      patients, we wondered whether also severely fatigued girls from a healthy
      population would show comparable alterations in psychological and immunological
      parameters. We tested this hypothesis in a longitudinal design, allowing a
      reliable assessment of the participants' characteristic immune status. Groups of
      severely fatigued (N=67) and non-fatigued (N=61) participants were selected.
      Severely fatigued girls reported more depressive symptoms, anxiety, reduced sleep
      quality, and somatic and CFS-related symptoms than non-fatigued participants
      across three measurements during one year (T1: spring, T2: autumn, T3: spring).
      In contrast, no group differences in mitogen-induced cytokine production or T
      cell proliferation in vitro or in leukocyte subset counts were observed. Although
      absolute cytokine production and cell counts were affected by seasonal variation,
      the within-subject values, relatively to the rest of the participants, were
      fairly stable. Data from a small group of CFS patients (N=11) showed similarities
      in self-reported complaints between CFS patients and fatigued participants.
      Interestingly, CFS patients showed a distinct immune profile when compared to the
      severely fatigued or non-fatigued participants, i.e. increased levels of anti
      inflammatory cytokines (IL-10, decreased IFN-gamma/IL-10 ratio) and reduced
      levels of pro-inflammatory cytokines (IL-6, TNF-alpha) over all three time points
      analyzed. These results show that, although overlap in symptomatology between the
      general population and patients with CFS was observed, only CFS patients show a
      skewing of the cytokine balance towards an anti-inflammatory profile.

PMID- 17544256
TI  - Distribution and morphology of putative catecholaminergic and serotonergic
      neurons in the medulla oblongata of a sub-adult giraffe, Giraffa camelopardalis.
AB  - The current study details the nuclear parcellation and appearance of putative
      catecholaminergic and serotonergic neurons within the medulla oblongata of a sub
      adult giraffe, using immunohistochemistry for tyrosine hydroxylase and serotonin.
      We hypothesized that the unusual phenotype of the giraffe, this being the long
      neck and potential axonal lengthening of these neurons, may pose specific
      problems in terms of the efficient functioning of these systems, as several
      groups of catecholaminergic and serotonergic neurons, especially of the medulla,
      are known to project to the entire spinal cord. This specific challenge may lead
      to observable differences in the nuclear parcellation and morphology of these
      systems in the giraffe. Our personal observations in the giraffe reveal that, as
      with other Artiodactyls, the spinal cord extends to the caudal end of the sacral
      vertebrae. Within the giraffe medulla we found evidence for five putative
      catecholaminergic (neurons containing tyrosine hydroxylase) and five serotonergic
      nuclei. In terms of both morphological appearance of the neurons and nuclear
      parcellation we did not find any evidence for features that may be considered
      affected by the phenotype of the giraffe. The nuclear parcellation and appearance
      of both the putative catecholaminergic and serotonergic systems in the medulla of
      the giraffe studied are strikingly similar to that seen in previous studies of
      other Artiodactyls. We interpret these findings in terms of a growing literature
      detailing order specific phylogenetic constraints in the evolution of these
      neuromodulatory systems.

PMID- 17544257
TI  - Multiple proteins mediate IQGAP1-stimulated cell migration.
AB  - Cell migration, a highly complex physiological phenomenon that requires the co
      ordinated and tightly regulated function of several proteins, is mediated by a
      number of signalling pathways. Elucidation of the molecular mechanisms of cell
      migration impacts our comprehension of numerous cell functions, ranging from
      development and immune surveillance to angiogenesis and metastasis. The scaffold
      protein IQGAP1, which binds multiple proteins and regulates their functions,
      promotes cell motility. Many of the IQGAP1 binding proteins have been implicated
      in cell migration. In this study, we employed a multifaceted strategy to identify
      proteins that contribute to IQGAP1-stimulated cell migration. Using specific
      IQGAP1 point mutant constructs, an interaction with actin was shown to be
      essential for IQGAP1 to increase cell migration. In contrast, eliminating the
      binding of Ca(2+)/calmodulin, but not Ca(2+)-free calmodulin, augmented the
      ability of IQGAP1 to stimulate cell migration. Consistent with these findings,
      selective inhibition of calmodulin function at the plasma membrane with a
      specific peptide inhibitor enhanced cell migration mediated by IQGAP1.
      Interestingly, immunofluorescence staining and confocal microscopy suggest that
      localization of Cdc42 at the leading edge is not necessary for maximal migration
      of epithelial cells. Coupled with the observations that Cdc42 and Rac1 contribute
      to IQGAP1-stimulated cell migration, these data suggest that IQGAP1 serves as a
      junction to integrate multiple signalling molecules to facilitate cell migration.

PMID- 17544258
TI  - Pentylenetetrazol kindling alters adenine and guanine nucleotide catabolism in
      rat hippocampal slices and cerebrospinal fluid.
AB  - Pentylenetetrazol (PTZ) is commonly used as a convulsant drug. The enhanced
      seizure susceptibility induced by kindling is probably attributable to plastic
      changes in the synaptic efficacy. Adenosine and guanosine act both as important
      neuromodulators and neuroprotectors with mostly inhibitory effects on neuronal
      activity. Adenosine and guanosine can be released per se or generated from
      released nucleotides (ATP, ADP, AMP, GTP, GDP, and GMP) that are metabolized and
      rapidly converted to adenosine and guanosine. The aim of this study was to
      evaluate nucleotide hydrolysis by ecto- and soluble nucleotidases (hippocampal
      slices and CSF, respectively) after PTZ-kindling (stages 3, 4, or 5 seizures) or
      saline treatment in rats. Additionally, the levels of purines in rat
      cerebrospinal fluid (CSF), as well as ecto-NTPDases (1, 2, 3, 5, 6 and 8) and
      ecto- 5'-nucleotidase expression were determined. Ecto-enzyme assays demonstrated
      that ATP, AMP, GDP, and GMP hydrolysis enhanced when compared with controls. In
      addition, there was an increase of ADP, GDP, and GMP hydrolysis by soluble
      nucleotidases in PTZ-kindling rats compared to control group. The HPLC analysis
      showed a marked increase in PTZ-kindled CSF concentrations of GTP, ADP, and uric
      acid, but GDP, AMP, and hypoxanthine concentrations were decreased. Such
      alterations indicate that the modulatory role of purines in CNS could be affected
      by PTZ-kindling. However, the physiological significance of these findings
      remains to be elucidated.

PMID- 17544259
TI  - Factors triggering abolishment of benzodiazepines effects in the Four-Plate Test-
      retest in mice.
AB  - Abolishment of anxiolytic-like effects of diazepam occurs during re-exposure to
      some animal tests of anxiety. We investigated the loss of anxiolytic-like effects
      of diazepam during Trial 2 on previously undrugged mice, namely one-trial
      tolerance (OTT). Swiss mice were subjected to 1) Four-Plate Test (FPT) without
      punishments in Trial 1 or 2) FPT without punishments in both Trials or 3) FPT
      with spatial modifications in Trial 1 or 4) Elevated Plus Maze (EPM), then 24 h
      later to FPT, with saline, diazepam (1 mg/kg) or DOI (1 mg/kg). Removing
      punishments in Trial 1 does not counteract the effect reduction of diazepam in
      Trial 2, but spatial modifications of the aversive environment. Previous exposure
      to EPM does not trigger a loss of efficacy of diazepam in FPT. Electric
      punishments do not trigger OTT to benzodiazepines; whilst knowledge of the
      environment seems to be responsible for this phenomenon. FPT may be useful to
      study OTT because punishments potentate OTT in this model of anxiety.

PMID- 17544260
TI  - Comparison of the interaction of dihydrocholesterol and cholesterol with
      sphingolipid or phospholipid Langmuir monolayers.
AB  - We report here a study of the interaction of dihydrocholesterol (DChol) with
      palmitoyl-oleoyl-phosphatidylcholine (POPC) or sphingomyelin (SM) in Langmuir
      monolayers. DChol and cholesterol (Chol) have very close chemical structures, and
      DChol is often used in place of Chol because of its better stability. Surface
      pressure measurements and experiments of desorption induced by beta-cyclodextrin
      show that POPC-DChol monolayers behave similarly to POPC-Chol ones: condensing
      effects of DChol and Chol on POPC and desorption percentages are in the same
      range. Moreover Brewster angle microscopy (BAM) experiments performed on these
      monolayers show that on the whole they are both homogenous. The analysis of mean
      molecular areas versus DChol percentage shows that this sterol is also able to
      induce SM condensation at low surface pressure. The condensation of SM molecules
      is particularly strong at 30 mol% of DChol. At higher surface pressure, the
      condensation efficiency of DChol decreases and monolayers behave more ideally,
      even if an inflection point is always observed at 30 mol% of DChol. However,
      desorption percentages, clearly lower than those obtained with POPC-DChol
      monolayers, show that DChol is kept at the interface. At last BAM images show
      also differences in the behaviour of SM-DChol and SM-Chol monolayers. These
      differences could be due to the different compressibility and conformation of the
      A/B rings in the two sterols and the rigidity of the sphingosine chain. They
      suggest that the use of DChol in place of Chol has to be done carefully in the
      presence of SM.

PMID- 17544261
TI  - [Characteristics of smoker adolescents seeking smoking cessation services].
AB  - In France, the prevalence of tobacco consumption is 31% for teenagers between 15
      and 19 years old. Nevertheless, few French studies have been published on the
      characteristics of young smokers seeking smoking cessation services. The
      development of smoking cessation centres in France since 1999 was associated to
      the setting up of a e-transfer system in order to evaluate the adequacy between
      these services and the needs of smokers. OBJECTIVE: To analyse the
      characteristics of smokers aged less than 19 years registered in the smoking
      cessation services national database. METHODS: A cross-sectional population-based
      study has been conducted in the smoking cessation services participating in the
      national database. The study population included 321 young smokers attending the
      smoking cessation centres during the period 2001-2005. RESULTS: The 321 smokers
      (mean age 16.6 years) were mostly girls (56.4%). A background of depression was
      declared by 19% of young smokers and an abnormal result was found for the
      hospital anxiety depression-screening test among 34% of the population for the
      anxiety scale and 6% for the depression scale. Mean daily tobacco consumption was
      15.3 cigarettes per day and heavy nicotine dependence was found for 24.1% of the
      population. A nicotine replacement therapy was prescribed for every smoker.
      CONCLUSION: Nicotine dependence was heavy for 24.1% of the 321 young smokers
      seeking smoking cessation services. More than 1/3 had an abnormal result for the
      hospital anxiety depression-screening test. Tailored interventions for smoking
      cessation should be available for adolescent's smokers, especially school-based
      services.

PMID- 17544262
TI  - A computational model to protect patient data from location-based re
      identification.
AB  - OBJECTIVE: Health care organizations must preserve a patient's anonymity when
      disclosing personal data. Traditionally, patient identity has been protected by
      stripping identifiers from sensitive data such as DNA. However, simple automated
      methods can re-identify patient data using public information. In this paper, we
      present a solution to prevent a threat to patient anonymity that arises when
      multiple health care organizations disclose data. In this setting, a patient's
      location visit pattern, or "trail", can re-identify seemingly anonymous DNA to
      patient identity. This threat exists because health care organizations (1) cannot
      prevent the disclosure of certain types of patient information and (2) do not
      know how to systematically avoid trail re-identification. In this paper, we
      develop and evaluate computational methods that health care organizations can
      apply to disclose patient-specific DNA records that are impregnable to trail re
      identification. METHODS AND MATERIALS: To prevent trail re-identification, we
      introduce a formal model called k-unlinkability, which enables health care
      administrators to specify different degrees of patient anonymity. Specifically, k
      unlinkability is satisfied when the trail of each DNA record is linkable to no
      less than k identified records. We present several algorithms that enable health
      care organizations to coordinate their data disclosure, so that they can
      determine which DNA records can be shared without violating k-unlinkability. We
      evaluate the algorithms with the trails of patient populations derived from
      publicly available hospital discharge databases. Algorithm efficacy is evaluated
      using metrics based on real world applications, including the number of
      suppressed records and the number of organizations that disclose records.
      RESULTS: Our experiments indicate that it is unnecessary to suppress all patient
      records that initially violate k-unlinkability. Rather, only portions of the
      trails need to be suppressed. For example, if each hospital discloses 100% of its
      data on patients diagnosed with cystic fibrosis, then 48% of the DNA records are
      5-unlinkable. A naive solution would suppress the 52% of the DNA records that
      violate 5-unlinkability. However, by applying our protection algorithms, the
      hospitals can disclose 95% of the DNA records, all of which are 5-unlinkable.
      Similar findings hold for all populations studied. CONCLUSION: This research
      demonstrates that patient anonymity can be formally protected in shared
      databases. Our findings illustrate that significant quantities of patient
      specific data can be disclosed with provable protection from trail re
      identification. The configurability of our methods allows health care
      administrators to quantify the effects of different levels of privacy protection
      and formulate policy accordingly.

PMID- 17544263
TI  - Use of monoclonal antibodies to assess expression of anaphylatoxin receptors in
      rat and murine models of lung inflammation.
AB  - The anaphylatoxins C3a and C5a are involved in the pathophysiology of microbial
      as well as allergic inflammation in the lungs. Besides their expression in
      leukocytes, receptors for C3a and C5a (C3aR and C5aR) have been noted in alveolar
      and bronchial epithelial cells, bronchial smooth muscle cells as well as in
      vascular endothelial and smooth muscle cells of normal and inflamed human and
      murine lungs. Recently, however, expression of anaphylatoxin receptors in
      parenchymal cells of the lung (and kidney) has been challenged. Using well
      characterized monoclonal antibodies (mabs) against murine and rat anaphylatoxin
      receptors, we reexamined the pulmonary distribution of C3aR and C5aR.
      Immunohistochemistry was performed on frozen sections of lung tissues from normal
      mice and rats as well as from animals subjected to lipopolysaccharide (LPS)
      induced inflammation or from MRL/lpr mice suffering from autoimmune disease.
      Furthermore, ovalbumin (OVA)-induced models of allergic asthma in the rat and
      mouse were investigated. Prominent expression of both anaphylatoxin receptors was
      detectable in resident as well as infiltrating leukocytes. No C3aR protein was
      observed in alveolar macrophages. Upon LPS- and OVA-challenge as well as in
      autoimmune inflammation, numbers of infiltrating leukocytes expressing prominent
      amounts of anaphylatoxin receptors increased. Even under these highly
      inflammatory conditions, however, expression of C3aR and C5aR was not inducible
      in parenchymal cells. Thus, our findings identify infiltrating leukocytes as a
      prominent source of anaphylatoxin receptors in inflamed lungs. A direct
      involvement of parenchymal cells in anaphylatoxin-mediated pulmonary inflammation
      is unlikely.

PMID- 17544264
TI  - Lung deposition and efficacy of inhaled formoterol in patients with moderate to
      severe COPD.
AB  - BACKGROUND: Little is known about the impact of COPD on lung deposition of
      inhaled drugs and the relationship between lung-dose and response of pulmonary
      function measurements. METHODS: Nineteen patients with varying degrees of COPD
      were randomized to inhale single doses of formoterol (Oxis) Turbuhaler 4.5, 9,
      18, and 36 microg in a double blind, placebo-controlled, crossover design.
      Urinary excreted formoterol during 32 h was used to determine absolute lung
      deposition. Peak inspiratory flow (PIF) and inhaled volume (IV) were recorded to
      assess the patients' ability to use Turbuhaler. Efficacy was measured by
      spirometry, inspiratory capacity (IC), airway conductance (sG(AW)), and absolute
      lung volumes. RESULTS: Mean pulmonary bioavailability of formoterol was about 24%
      of the nominal delivered dose after inhalation for the different treatments. No
      significant correlations between lung deposition and baseline FEV(1), PIF or IV
      were shown. All formoterol doses produced statistically significant increases in
      FEV(1), FVC, IC, and sG(AW) relative to placebo. Linear dose/response
      relationships were observed for these variables, with more narrow limits of the
      slopes for the lung-dose/response relationships than for the nominal
      dose/response relationships. Moreover, 36 and 18 microg formoterol statistically
      significantly decreased functional residual capacity (FRC) and residual volume
      (RV) relative to placebo. CONCLUSIONS: This study could not show any difference
      in lung deposition of formoterol inhaled via Turbuhaler between patients with
      moderate and severe COPD. Moreover, the effect of formoterol on various pulmonary
      function measurements were more closely related to lung deposition than the
      inhaled nominal dose.

PMID- 17544265
TI  - Sex differences in the incidence and severity of respiratory tract infections.
AB  - Sex is a significant epidemiological factor for several diseases. However, the
      role of sex in the development and outcome of various infections has not been
      extensively studied with the notable exception of urinary tract infections. We
      searched in the PubMed database to identify articles that could provide relevant
      data regarding sex differences in the incidence and severity of respiratory tract
      infections (RTIs). We extracted data from 84 relevant studies that provided
      information regarding sex differences in the incidence and severity of RTIs.
      Females are more commonly affected with infections of the upper respiratory
      tract, specifically sinusitis, tonsillitis, and otitis externa. On the other
      hand, males are more commonly affected with otitis media, croup, and most
      important, lower RTIs. It is also evident from the reviewed evidence that the
      course of most RTIs is more severe in males than in females, leading to higher
      mortality in males, especially in community-acquired pneumonia. In conclusion,
      the available data suggest that males are more susceptible than females to most
      types of RTIs in all age groups (adults and children). Overall, it seems that
      males develop RTIs more frequently than females, except for sinusitis, otitis
      externa, and probably tonsillitis. Anatomic, lifestyle, behavioural, and
      socioeconomic differences between males and females may explain the observed
      findings. The role of sex hormones in the regulation of the immune system may
      also contribute to the reported sex differences in the incidence and severity of
      the various types of RTIs, especially in adolescents and adults.

PMID- 17544266
TI  - Information about cancer clinical trials: an analysis of Internet resources.
AB  - PURPOSE: Clinical trials are critical to improving patient outcomes, but
      participation in cancer clinical trials is low. Patient understanding of clinical
      trial process is also limited. Patients are increasingly using the Internet as a
      source of information. It is critical that such Internet-based information is
      relevant, current, balanced, and easy to access and navigate. We critically
      reviewed seven international online resources that provide information for
      patients/consumers regarding cancer clinical trials. METHODS: Seven international
      websites from North America, Europe and Australia were selected based on
      profile/usage. Sites were evaluated with respect to their content, readability
      and appropriateness using a suite of standard assessment tools. RESULTS: No sites
      performed well in terms of all assessment criteria. There was substantial
      variation between sites regarding information provided, content, design and
      readability. All sites required high literacy levels and assessment using the
      Standard Assessment of Means tool showed consistent deficiencies. CONCLUSION:
      Although there are numerous websites providing information about cancer clinical
      trials to patients/consumers, all evaluated sites have several shortcomings.
      Attention to the content of information, its presentation and the design of
      Internet resources has an ethical imperative, and is likely to lead to improved
      patient satisfaction.

PMID- 17544267
TI  - Co-digestion of onion juice and wastewater sludge using an anaerobic mixed
      biofilm reactor.
AB  - The co-digestion of onion juice and aerobic wastewater sludge produced from an
      onion processor using an anaerobic mixed biofilm reactor (AMBR) was investigated
      for biogas energy production potential and waste treatment. Two experiments were
      conducted to study the performance of an AMBR at different organic loading rates
      (OLRs) using different mixtures of onion juice and aerobic sludge. In the first
      experiment, the OLR was increased from 1.24 to 4.37 gVS/L/d by increasing the
      amount of onion juice in the feed mixture while maintaining a constant amount of
      aerobic sludge. When the OLR reached 4.37 gVS/L/d, the AMBR failed as indicated
      by decreased biogas production and pH. Increase of carbon to nitrogen ratio (C/N)
      from 13.7 to 20.3 and lack of proper alkalinity were suspected to be the causes
      for the failure. In the second experiment, the C/N of the feed mixture was
      maintained at about 15 while the OLR was increased from 1.40 to 3.60 gVS/L/d. The
      digester showed stable performance. The average biogas and methane yields of the
      two experiments were 0.62 +/- 0.05 L/gVS and 0.37 +/- 0.08 L/gVS, respectively.
      It was concluded that the C/N of about 15 was recommended for treating the
      mixture of onion juice and aerobic sludge.

PMID- 17544268
TI  - Ellagic acid from acorn fringe by enzymatic hydrolysis and combined effects of
      operational variables and enzymes on yield of the production.
AB  - The individual effects of three different enzyme types -- one single enzyme
      (ellagitannin acyl hydrolase) and two combinations of enzymes (ellagitannin acyl
      hydrolase-beta-glucosidase-polyphenol oxidase and ellagitannin acyl hydrolase
      cellulase-xylanase) -- on ellagic acid yield, combined with other process
      parameters -- enzyme concentration, hydrolysis time, particle size and solid-to
      liquid ratio -- were evaluated by response surface methodology. The selection of
      the enzymes for the study was based on preliminary experiments that showed higher
      increments in ellagic acid yield. The quantitative parameters studied were enzyme
      concentration (0.1, 0.45, 2 w/w or %), solid-to-liquid ratio (0.05, 0.15, 0.2),
      particle size (220, 445, 900 microm) and hydrolysis time (60, 89, 132 min).
      Experimental data for ellagic acid yield obtained with a single enzyme and two
      combination enzymes correlated very well with process parameters (P<0.0001),
      resulting in models with high coefficient of determination for ellagic acid yield
      (r(2)=0.9636). The combinations of enzymes appeared more effective for ellagic
      acid production than the single enzyme did. The yield of ellagic acid from non
      heat-treated acorn fringe by the use of enzymes in general increased, compared
      with that from heat-treated material. The research opens a technological
      efficient way and develop easily-available renewable raw material for ellagic
      acid production.

PMID- 17544269
TI  - Primary amides as selective inhibitors of cathepsin K.
AB  - The nitrile warhead used in a series of cathepsin K inhibitors can be replaced by
      a less electrophilic primary amide. The accompanying loss of potency can be
      partially recovered by introducing a substituent alpha to the amide. The potency
      gain resulting from this addition is not achieved with the nitrile derivatives
      due to a different geometry of the cysteine adduct in the enzyme active site.
      This study led to the identification of the primary amide 2g, which is an
      inhibitory substrate, with an IC(50) of 10 nM against cathepsin K and excellent
      selectivity versus the other cathepsins.

PMID- 17544270
TI  - (2R,3S)-(+)- and (2S,3R)-(-)-Halofuginone lactate: synthesis, absolute
      configuration, and activity against Cryptosporidium parvum.
AB  - The trans-enantiomers of the commercially important anti-protozoal compound
      Halofuginone have been prepared and characterized, and the absolute configuration
      was assigned by X-ray crystallography. The activity of both enantiomers against
      Cryptosporidium parvum was determined in vitro and related to acute toxicity in
      vivo. It was shown that both the activity and the toxicity are properties of the
      (2R,3S)-enantiomer. We conclude that with respect to broadening the therapeutic
      window there is no advantage in application of one enantiomer over the
      application of the racemic mixture in the treatment of C. parvum infections.

PMID- 17544271
TI  - Synthesis and biological evaluation of 4'-(6,7-disubstituted-2,4-dihydro
      indeno[1,2-c]pyrazol-3-yl)-biphenyl-4-ol as potent Chk1 inhibitors.
AB  - A new series of potent tricyclic pyrazole-based Chk1 inhibitors are described.
      Analogues disubstituted on the 6- and 7-positions show improved Chk1 inhibition
      potency compared with analogues with a single substituent on either the 6- or 7
      position. Based on the lead compound 4'-(6,7-dimethoxy-2,4-dihydro-indeno[1,2
      c]pyrazol-3-yl)-biphenyl-4-ol (2), detailed SAR studies on the 6- and 7-positions
      were performed. 3'-morpholin-4'-yl-propoxy, pyridin-4'-ylmethoxy, pyridin-3'
      ylmethoxy, 2'-(5''-ethyl-pyridin-2''-yl)-ethoxy, pyridin-2'-ylethoxy, (6'-methyl
      pyridin-2'-yl)-propoxyethoxy, 2',3'-dihydroxyl-1'-yl-propoxy, and tetrahydro
      furan-3'-yloxy have been identified as the best groups on the 6-position when the
      7-position is substituted with methoxyl group. Pyridin-2'-ylmethoxy and pyridin
      3'-ylmethoxy have been identified as the best substituents at the 7-position
      while the 6-position bearing methoxyl group. These compounds significantly
      potentiate the cytotoxicity of DNA-damaging antitumor agents in a cell-based
      assay and efficiently abrogate the doxorubicin-induced G2/M and the camptothecin
      induced S checkpoints, suggesting that their potent biological activities are
      mechanism-based through Chk1 inhibition.

PMID- 17544272
TI  - Indolinone based phosphoinositide-dependent kinase-1 (PDK1) inhibitors. Part 2:
      optimization of BX-517.
AB  - Based on the lead compound BX-517, a series of C-4' substituted indolinones have
      been synthesized and evaluated for PDK1 inhibition. Modification at C-4' of the
      pyrrole afforded potent compounds (7b and 7d) with improved solubility and ADME
      properties. In this letter, we describe the synthesis, selectivity profile, and
      pharmacokinetic data of selected compounds.

PMID- 17544273
TI  - Roll-over shapes of the able-bodied knee-ankle-foot system during gait
      initiation, steady-state walking, and gait termination.
AB  - A few investigators have described the movement of the center of pressure (COP)
      of the ground reaction force and the activation patterns of the lower limb
      muscles during gait initiation and termination. This study examines the effective
      rocker (roll-over shape) behavior of the knee-ankle-foot (KAF) system during gait
      initiation, steady-state walking (i.e. constant speed gait), and gait
      termination. The KAF roll-over shapes were characterized by transforming COP data
      of 10 able-bodied subjects from a laboratory-based coordinate system into a leg
      based coordinate system. The resulting roll-over shapes (effective rockers) were
      characterized using a circular arc model. The KAF roll-over shapes exhibit an
      overall "flexed" orientation during the first step of gait initiation and an
      "extended" orientation during the last step of gait termination. Understanding
      the behavior of the anatomical KAF system during gait initiation and termination
      may aid in the design of prosthetic components, i.e. mechanical devices that
      replace complete anatomical structures. Prostheses that intend to mimic the
      overall behavior of physiological KAF systems (biomimetic designs) could be
      manufactured using approaches that are much simpler than attempting to
      reconstruct the complexity of the lower limb.

PMID- 17544274
TI  - Tibial torsion: significance and measurement.

PMID- 17544275
TI  - Cognitive impairment patterns in Parkinson's disease with visual hallucinations.
AB  - OBJECTIVES: We investigated the role of stage of disease, motor status and
      dopaminergic treatment in cognitive impairment of Parkinson's disease (PD)
      patients with visual hallucination (VH) and the presence of specific cognitive
      impairment patterns. METHOD: We compared 33 PD patients with VH (group 1) with 30
      PD patients without VH (group 2) with regard to demographic characteristics and
      neuropsychological test scores. RESULTS: The group with VH demonstrated
      significantly worse Short Test of Mental Status scores; the cognitive impairment
      pattern presented in the form of frontal dysfunction and memory deterioration.
      There were significant differences in Stroop duration/error, verbal fluency,
      Wechsler Memory Scale and Sozel Bellek Surecleri Test (a Turkish verbal learning
      test) scores. CONCLUSION: In PD patients with VH the main pattern of cognitive
      impairment is frontal dysfunction and memory deterioration. Because visual
      perceptive functions were not different between the two groups, such
      deterioration may not be a primary factor in the development of VH.

PMID- 17544276
TI  - Disaccharide analogs as probes for glycosyltransferases in Mycobacterium
      tuberculosis.
AB  - Glycosyltransferases (GTs) play a crucial role in mycobacterial cell wall
      biosynthesis and are necessary for the survival of mycobacteria. Hence, these
      enzymes are potential new drug targets for the treatment of tuberculosis (TB),
      especially multiple drug-resistant TB (MDR-TB). Herein, we report the efficient
      syntheses of Araf(alpha 1-->5)Araf, Galf(beta 1-->5)Galf, and Galf(beta 1-
      >6)Galf disaccharides possessing a 5-N,N-dimethylaminonaphthalene-1
      sulfonamidoethyl (dansyl) unit that were prepared as fluorescent disaccharide
      acceptors for arabinosyl- and galactosyl-transferases, respectively. Such analogs
      may offer advantages relative to radiolabeled acceptors or donors for studying
      the enzymes and for assay development and compound screening. Additionally,
      analogs possessing a 5-azidonaphthalene-1-sulfonamidoethyl unit were prepared as
      photoaffinity probes for their potential utility in studying active site labeling
      of the GTs (arabinosyl and galactosyl) in Mycobacterium tuberculosis (MTB).
      Beyond their preparation, initial biological testing and kinetic analysis of
      these disaccharides as acceptors toward glycosyltransferases are also presented.

PMID- 17544278
TI  - Synthesis and structure-activity relationships study of novel anti-tumor
      carbamate anhydrovinblastine analogues.
AB  - A series of 3-demethoxycarbonyl-3-carbamate methyl anhydrovinblastine derivatives
      (compounds 8b-32b) were designed, synthesized, and evaluated for their inhibition
      activities against human non-small cell lung cancer cell line (A549) and a human
      cervix epithelial adenocarcinoma cell line (HeLa). The structure-activity
      relationships of this new series are described in this paper. Cytotoxicity data
      revealed that the size of substituents and substitution position had important
      influence on cytotoxic activity. On two cell lines, compounds (8b and 30b) had
      more potent cytotoxic activity than the lead compound (1e, AVLB). The preliminary
      antitumor studies of 8b in vivo showed that it might be promising for the
      development of new antitumor agents.

PMID- 17544277
TI  - Targeting cytochrome P450 enzymes: a new approach in anti-cancer drug
      development.
AB  - Cytochrome P450s (CYPs) represent a large class of heme-containing enzymes that
      catalyze the metabolism of multitudes of substrates both endogenous and
      exogenous. Until recently, however, CYPs have been largely overlooked in cancer
      drug development, acknowledged only for their role in phase I metabolism of
      chemotherapeutics. The first successful strategy targeting CYP enzymes in cancer
      therapy was the development of potent inhibitors of CYP19 (aromatase) for the
      treatment of breast cancer. Aromatase inhibitors ushered in a new era in hormone
      ablation therapy for estrogen dependent cancers, and have paved the way for
      similar strategies (i.e., inhibition of CYP17) that combat androgen dependent
      prostate cancer. Identification of CYPs involved in the inactivation of anti
      cancer metabolites of vitamin D(3) and vitamin A has triggered development of
      agents that target these enzymes as well. The discovery of the over-expression of
      exogenous metabolizing CYPs, such as CYP1B1, in cancer cells has roused interest
      in the development of inhibitors for chemoprevention and of prodrugs designed to
      be activated by CYPs only in cancer cells. Finally, the expression of CYPs within
      tumors has been utilized in the development of bioreductive molecules that are
      activated by CYPs only under hypoxic conditions. This review offers the first
      comprehensive analysis of strategies in drug development that either inhibit or
      exploit CYP enzymes for the treatment of cancer.

PMID- 17544279
TI  - A para-amino substituent on the D-ring of green tea polyphenol epigallocatechin-3
      gallate as a novel proteasome inhibitor and cancer cell apoptosis inducer.
AB  - Analogs of (-)-EGCG containing a para-amino group on the D-ring in place of the
      hydroxyl groups have been synthesized and their proteasome inhibitory activities
      were studied. We found that, the O-acetylated (-)-EGCG analogs possessing a p
      NH(2) or p-NHBoc (Boc; tert-butoxycarbonyl) D-ring (5 and 7) act as novel tumor
      cellular proteasome inhibitors and apoptosis inducers with potency similar to
      natural (-)-EGCG and similar to (-)-EGCG peracetate. These data suggest that the
      acetylated amino-GTP analogs have the potential to be developed into novel
      anticancer agents.

PMID- 17544280
TI  - Synthesis, 3D-QSAR, and docking studies of 1-phenyl-1H-1,2,3-triazoles as
      selective antagonists for beta3 over alpha1beta2gamma2 GABA receptors.
AB  - A series of 16 1-phenyl-1H-1,2,3-triazoles with substituents at both the 4- and 5
      positions of the triazole ring were synthesized, and a total of 49 compounds,
      including previously reported 4- or 5-monosubstituted analogues, were examined
      for their ability to inhibit the specific binding of [(3)H]4'-ethynyl-4-n
      propylbicycloorthobenzoate (EBOB), a non-competitive antagonist, to human homo
      oligomeric beta3 and hetero-oligomeric alpha1beta2gamma2 gamma-aminobutyric acid
      (GABA) receptors. Among all tested compounds, the 4-n-propyl-5-chloromethyl
      analogue of 1-(2,6-dichloro-4-trifluoromethylphenyl)-1H-1,2,3-triazole showed the
      highest level of affinity for both beta3 and alpha1beta2gamma2 receptors, with
      K(i) values of 659pM and 266nM, respectively. Most of the tested compounds showed
      selectivity for beta3 over alpha1beta2gamma2 receptors. Among all 1-phenyl-1H
      1,2,3-triazoles, the 4-n-propyl-5-ethyl analogue exhibited the highest (>1133
      fold) selectivity, followed by the 4-n-propyl-5-methyl analogue of 1-(2,6-dibromo
      4-trifluoromethylphenyl)-1H-1,2,3-triazole with a >671-fold selectivity. The 2,6
      dichloro plus 4-trifluoromethyl substitution pattern on the benzene ring was
      found to be important for the high affinity for both beta3 and alpha1beta2gamma2
      receptors. Comparative molecular field analysis (CoMFA) and comparative molecular
      similarity indices analysis (CoMSIA) provided similar contour maps, revealing
      that an electronegative substituent at the 4-position of the benzene ring, a
      compact, hydrophobic substituent at the 4-position of the triazole ring, and a
      small, electronegative substituent at the 5-position of the triazole ring play
      significant roles for the high potency in beta3 receptors. Molecular docking
      studies suggested that the putative binding sites for 1-phenyl-1H-1,2,3-triazole
      antagonists are located in the channel-lining 2'-6' region of the second
      transmembrane segment of beta3 and alpha1beta2gamma2 receptors. A difference in
      the hydrophobic environment at the 2' position might underlie the selectivity of
      1-phenyl-1H-1,2,3-triazoles for beta3 over alpha1beta2gamma2 receptors. The
      compounds that had high affinity for beta3 receptors with homology to insect GABA
      receptors showed insecticidal activity against houseflies with LD(50) values in
      the pmol/fly range. The information obtained in the present study should prove
      helpful for the discovery of selective insect control chemicals.

PMID- 17544281
TI  - Synthesis, characterization and antimicrobial activity of new aliphatic
      sulfonamide.
AB  - A series of novel aliphatic sulfonamide derivatives (1-7) were synthesized and
      characterized by elemental analyses, FT-IR, (1)H NMR, (13)C NMR and LC-MS
      techniques. All the synthesized compounds were evaluated in vitro as
      antimicrobial agents against representative strains of Gram-positive
      (Staphylococcus aureus ATCC 25953, Bacillus cereus ATCC 6633 and Listeria
      monocytogenes ATCC Li6 (isolate), Gram-negative bacteria (Escherichia coli ATCC
      11230) and antifungal agent against Candida albicans (clinical isolate) by both
      disc diffusion and minimal inhibition concentration (MIC) methods. All these
      bacteria and fungus studied were screened against some antibiotics to compare
      with our chemicals' zone diameters. Our aliphatic sulfonamides have highest
      powerful antibacterial activity for Gram-negative bacteria than Gram-positive
      bacteria and antibacterial activity decreases as the length of the carbon chain
      increases.

PMID- 17544282
TI  - Pyrrolidinones as orally bioavailable antagonists of the human melanocortin-4
      receptor with anti-cachectic activity.
AB  - A series of pyrrolidinones derived from phenylalanines were synthesized as potent
      antagonists of the human melanocortin-4 receptor. These compounds showed high
      potencies and selectivities, and several of them had good oral bioavailabilities.
      In addition, 12e demonstrated in vivo efficacy in a murine cachexia model.

PMID- 17544284
TI  - Comments on "a comparison of different analytical methods of determining the
      solid angle of a circular coaxial source-detector system".

PMID- 17544283
TI  - Automated synthesis of 11C-acetoacetic acid, a key alternate brain fuel to
      glucose.
AB  - An automated, one-pot radio-synthesis module for the routine preparation of 1
      [(11)C]acetoacetic acid has been developed. The enolate anion of acetone was
      reacted with [(11)C]CO(2) in tetrahydrofuran (THF), followed by hydrolysis and
      purification by ion-exchange chromatography. The total synthesis time was 18 min
      and radiochemical yield was 34% after decay correction. HPLC analysis showed < or
      =3% impurities while residual THF (< or =200 ppm) and ethanol (< or =500 ppm)
      were well under the tolerable limits for human studies.

PMID- 17544285
TI  - Interleukin 10 and TNFalpha synergistically enhance the expression of the G
      protein-coupled formylpeptide receptor 2 in microglia.
AB  - Microglia are important participants in inflammatory responses in the central
      nervous system. We previously observed that tumor necrosis factor alpha
      (TNFalpha) induces the expression of the formylpeptide receptor mFPR2 on
      microglial cells. This chemoattractant receptor mediates microglial cell
      chemotaxis in response to a variety of peptides, including amyloid beta peptide
      (Abeta(42)), a major pathogenic factor in Alzheimer's disease (AD). In search for
      agents that regulate microglial activation, we unexpectedly found that IL-10
      enhanced the expression of mFPR2 on TNFalpha-activated microglia. This was
      associated with a markedly increased microglial chemotaxis to Abeta(42) and its
      endocytosis via mFPR2. Mechanistic studies revealed that the synergistic effect
      of IL-10 on TNFalpha-induction of mFPR2 in microglia was dependent on activation
      of p38 MAPK. Our results suggest that IL-10 may affect the pathogenic process of
      AD by up-regulating mFPR2 and thus favoring the recognition and internalization
      of Abeta(42) by activated microglial cells.

PMID- 17544286
TI  - Treatment of chickpea with Rhizobium isolates enhances the expression of
      phenylpropanoid defense-related genes in response to infection by Fusarium
      oxysporum f. sp. ciceris.
AB  - Differential expression of phenylalanine ammonia-lyase (PAL), chalcone synthase
      (CHS) and isoflavone reductase (IFR) genes involved in phenylpropanoids
      metabolism was investigated using Northern blot analyses in chickpea seedlings
      bacterized with Rhizobium isolates (PchDMS and Pch43) and further challenged with
      Fusarium oxysporum f. sp. ciceris (Foc) race 0. Gene activation patterns in the
      moderately resistant accession INRAT87/1 were compared with those exhibited by
      the susceptible accession ILC482 at various time intervals after inoculation with
      Foc, to determine whether differences in levels or timing of transcript
      accumulation could be correlated with differences in the susceptibility of
      chickpea accessions to Foc. Gene activation was higher in the moderately
      resistant accession INRAT87/1 than in the susceptible ILC482. Pre-treatment of
      chickpea seedlings with Rhizobium isolates before inoculation with the pathogen
      enhanced the accumulation of the three genes' mRNA transcripts. In parallel,
      changes in the soluble phenolic pool produced through pathways involving these
      enzymes were analyzed in chickpea roots. A strong accumulation of these compounds
      was revealed at 72 hpi in both accessions. After that time, these high levels of
      phenolic compounds were maintained until the end of the experiment in the
      moderately resistant accession, while they have significantly declined in the
      susceptible accession. HPLC analyses revealed a very high accumulation of the
      constitutive isoflavones, formononetin and biochanin A and their glycoside
      conjugates in chickpea roots inoculated with Rhizobium isolates and/or challenged
      with Foc, as compared to the controls. Our results suggest that the increased
      accumulation of phenolic compounds, observed in chickpea seedlings inoculated
      with Foc, can be attributed to increased expression of genes in the
      phenylpropanoid pathway and that such gene expression is enhanced by pre
      treatment with Rhizobium isolates.

PMID- 17544287
TI  - Responses of transformed Catharanthus roseus roots to femtomolar concentrations
      of salicylic acid.
AB  - Catharanthus roseus transformed roots were cultured in the presence of salicylic
      acid (SA) at concentrations between 0.1 fM and 100 pM and the effect on root
      growth was evaluated. Significant morphological changes in the lateral roots were
      recorded on day two in the SA treatment. Presence of SA increased root cap size
      and caused the appearance of lateral roots closer to the root tip. The bioassay
      was sensitive enough to allow testing of low concentrations of other growth
      regulators that may affect root morphology and physiology.

PMID- 17544288
TI  - A predicted N-terminal helical domain of a Group 1 LEA protein is required for
      protection of enzyme activity from drying.
AB  - Late embryogenesis abundant (LEA) proteins have been repeatedly implicated in the
      acquisition of desiccation tolerance in angiosperm seed embryos. However, the
      mechanism(s) by which protection occurs is not well understood. While the Group 1
      LEA proteins are predicted to be largely unordered in solution, there is strong
      evidence that upon drying these proteins undergo a structural transition that
      leads to an increase in alpha-helical content. Several studies also suggest there
      is a direct interaction between Group 1 LEA proteins and other molecules in the
      cytoplasm that may be critical for the establishment of desiccation tolerance
      during embryo maturation. We have produced a recombinant Group 1 LEA protein and
      show that it is capable of protecting the enzyme lactate dehydrogenase from the
      deleterious effects of drying. We have also evaluated the ability of various
      altered recombinant Group 1 LEA proteins to protect in the same assay. Our
      results suggest that the highly conserved 20 amino acid Group 1 LEA signature
      motif is not required for protection in our in vitro assay. However, introduction
      of two juxtaposed proline residues into an N-terminal helical domain predicted to
      exist in the hydrated structure significantly compromises the ability of the
      recombinant protein to provide protection from drying. These results suggest that
      the N-terminal domain of Group 1 LEA proteins may be important for proper folding
      during dehydration.

PMID- 17544289
TI  - DNA-damage sensitizers: potential new therapeutical tools to improve
      chemotherapy.
AB  - Agents that induce DNA damage in cells--the so-called genotoxins--have
      successfully been used for decades to treat patients with tumors. Genotoxins
      alter the DNA of cells, which is detected by DNA damage sensors and which leads
      to the activation of p53. Activation of p53 can lead to the death of cancer
      cells. The efficacy of genotoxins in humans is however limited by their toxicity
      to normal tissues. Specific sensitization of tumor cells to the action of
      genotoxins would reduce the efficacious doses of genotoxins to be used in
      patients, diminishing the detrimental side-effects of the drugs on normal
      tissues. A series of compounds able to sensitize cancer cells to DNA-damaging
      drugs have recently been identified that have the potential to increase the
      efficacy of currently used anti-cancer treatments.

PMID- 17544290
TI  - Chronic lymphocytic leukemia.
AB  - Chronic lymphocytic leukemia (CLL) is the most common adult leukemia in the
      western world and is due to the accumulation of mature B lymphocytes in the
      peripheral blood, bone marrow and secondary lymphoid organs. The leukemic cells
      show a distinct phenotype, which is essential to reach the correct diagnosis.
      Despite the phenotypic homogeneity, the clinical outcome may be significantly
      different. Some patients have an indolent leukemia, with long survival while
      others experience an aggressive disease, with early and frequent need of
      treatment. At present, no chemotherapeutic regimens can be considered curative
      and all patients will die with (or because of) their disease. In recent years,
      research on CLL has led to important discoveries that help defining patients'
      prognosis at the moment of diagnosis. These prognostic factors, which are derived
      from the biological features of the leukemic lymphocytes, are now rapidly moved
      into the clinical arena. They are used to stratify patients in selected clinical
      trials to assess the value of early and more modern treatments, which are
      becoming available to hematologists.

PMID- 17544291
TI  - ISWI chromatin remodeling in ovarian somatic and germ cells: revenge of the
      NURFs.
AB  - Chromatin has emerged as an important regulator of gene expression, interposed
      between cell signaling pathways and transcriptional machinery. It participates in
      transmitting extra- and intra-cellular signals that coordinate ovarian events:
      ovarian follicle development, the meiotic maturation of the oocyte that precedes
      ovulation, and the ovulatory process and consequent luteinization. Recent
      evidence from model organisms and mammals suggests that chromatin signaling is
      achieved, in part, by imitation switch (ISWI) ATP-dependent chromatin-remodeling
      complexes. This review highlights a role for complexes containing the ISWI ATPase
      sucrose nonfermenting-2h (Snf2h) in proliferation in somatic and germ cells and
      also in meiosis in germ cells. Moreover, complexes containing the Snf2l ATPase
      dictate the differentiation of somatic cells and act in the induction of the
      terminal phases of meiosis in the oocyte.

PMID- 17544292
TI  - Protein kinase C theta (PKCtheta): a key player in T cell life and death.
AB  - Protein kinase C theta (PKCtheta) is a member of the novel, Ca(2+)-independent
      PKC subfamily, which plays an important and non-redundant role in several aspects
      of T cell biology. Much progress has been accomplished in understanding the
      function of PKCtheta in the immune system and its unique translocation to the
      immunological synapse in Ag-stimulated T lymphocytes. Biochemical and genetic
      approaches revealed that PKCtheta is required for the activation of mature T
      cells as well as for their survival. Mutation of the PKCtheta gene leads to
      impaired receptor-induced stimulation of the transcription factors AP-1, NF
      kappaB and NFAT, which results in defective T cell activation, and to aberrant
      expression of apoptosis-related proteins, resulting in poor T cell survival.
      Furthermore, PKCtheta-deficient mice display defects in the differentiation of T
      helper subsets, particularly in Th2- and Th17-mediated inflammatory responses.
      Therefore, PKCtheta is a critical enzyme that regulates T cell function at
      multiple stages, and it represents an attractive drug target for allergic and
      autoimmune diseases.

PMID- 17544293
TI  - Sequencing of T-superfamily conotoxins from Conus virgo: pyroglutamic acid
      identification and disulfide arrangement by MALDI mass spectrometry.
AB  - De novo mass spectrometric sequencing of two Conus peptides, Vi1359 and Vi1361,
      from the vermivorous cone snail Conus virgo, found off the southern Indian coast,
      is presented. The peptides, whose masses differ only by 2 Da, possess two
      disulfide bonds and an amidated C-terminus. Simple chemical modifications and
      enzymatic cleavage coupled with matrix assisted laser desorption ionization
      (MALDI) mass spectrometric analysis aided in establishing the sequences of
      Vi1359, ZCCITIPECCRI-NH(2), and Vi1361, ZCCPTMPECCRI-NH(2), which differ only at
      residues 4 and 6 (Z = pyroglutamic acid). The presence of the pyroglutamyl
      residue at the N-terminus was unambiguously identified by chemical hydrolysis of
      the cyclic amide, followed by esterification. The presence of Ile residues in
      both the peptides was confirmed from high-energy collision induced dissociation
      (CID) studies, using the observation of w(n)- and d(n)-ions as a diagnostic.
      Differential cysteine labeling, in conjunction with MALDI-MS/MS, permitted
      establishment of disulfide connectivity in both peptides as Cys2-Cys9 and Cys3
      Cys10. The cysteine pattern clearly reveals that the peptides belong to the class
      of T-superfamily conotoxins, in particular the T-1 superfamily.

PMID- 17544294
TI  - A novel approach to analyze membrane proteins by laser mass spectrometry: from
      protein subunits to the integral complex.
AB  - A novel laser-based mass spectrometry method termed LILBID (laser-induced liquid
      bead ion desorption) is applied to analyze large integral membrane protein
      complexes and their subunits. In this method the ions are IR-laser desorbed from
      aqueous microdroplets containing the hydrophobic protein complexes solubilized by
      detergent. The method is highly sensitive, very efficient in sample handling,
      relatively tolerant to various buffers, and detects the ions in narrow, mainly
      low-charge state distributions. The crucial experimental parameter determining
      whether the integral complex or its subunits are observed is the laser intensity:
      At very low intensity level corresponding to an ultrasoft desorption, the intact
      complexes, together with few detergent molecules, are transferred into vacuum.
      Under these conditions the oligomerization state of the complex (i.e., its
      quaternary structure) may be analyzed. At higher laser intensity, complexes are
      thermolyzed into subunits, with any residual detergent being stripped off to
      yield the true mass of the polypeptides. The model complexes studied are derived
      from the respiratory chain of the soil bacterium Paracoccus denitrificans and
      include complexes III (cytochrome bc(1) complex) and IV (cytochrome c oxidase).
      These are well characterized multi-subunit membrane proteins, with the individual
      hydrophobic subunits being composed of up to 12 transmembrane helices.

PMID- 17544295
TI  - Expression, purification and characterization of human urodilatin in E. coli.
AB  - Urodilatin is a 32-amino acid peptide hormone synthesized in kidney to regulate
      natriuresis and diuresis. It has been shown clinically useful for the treatment
      of acute decompensated heart failure. A synthetic deoxyoligonucleotide encoding
      urodilatin was cloned into a pET32a vector immediately after the thioredoxin
      encoding sequence with a hexa-hisditine tag and an enterokinase recognition site
      incorporated in between. The fusion protein was overexpressed in Escherichia
      coli, which constituted 28% of the total cell proteins. More than 85% of Trx
      urodilatin was soluble and purified nearly homogenous by Ni-Sepharose affinity
      chromatography. Urodilatin was then released from the fusion protein by the
      enterokinase treatment and separated from the fusion partner by the subtractive
      chromatography using Ni-Sepharose once again. The urodilatin sample was further
      purified with reverse phase HPLC. Via a biological activity assayed in vitro, it
      was found that urodilatin had a potent vasodilatory effect on rabbit aortic
      strips with an EC50 of (2.02+/-0.36)x10(-6)mg/ml, which was similar to that of
      the synthetic urodilatin standard. The method described here promises to produce
      about 4.5mg fully active recombinant urodilatin with homogeneity over 97% from
      one liter shaking flask culture of E. coli.

PMID- 17544296
TI  - Treatment needs and completion of community-based aftercare among substance
      abusing women offenders.
AB  - BACKGROUND: Women offenders with substance abuse problems typically have many
      treatment needs on reentry to the community from prison. This paper explores the
      correlates of treatment needs among a sample of women offenders with substance
      abuse problems (n = 1,404), and the relationship between their treatment needs
      and other background characteristics with completion of community-based treatment
      after parole. METHODS: Treatment needs were assessed at admission into prison
      based substance abuse treatment; participants were admitted into community-based
      treatment upon parole. Descriptive statistics and multiple regression were used
      to examine their treatment needs; logistic regression analysis was used to
      determine the factors related to completion of the aftercare program. Analysis of
      variance was used to examine ethnic differences in treatment needs. RESULTS:
      Greater treatment needs were associated with unstable housing before
      incarceration, a history of sexual or physical abuse, mental health problems,
      alcohol or drug dependence, and first arrest at age <19; lower treatment needs
      were associated with having been mandated to prison-based treatment (versus
      volunteering). Mental health problems and earlier age at first arrest predicted
      treatment noncompletion. Drug dependence was associated with higher treatment
      needs and a greater likelihood of treatment completion, whereas African American
      and Hispanic ethnicity were both associated with lower treatment needs (compared
      with Whites) and a lower likelihood of treatment completion. CONCLUSIONS:
      Interventions are needed to engage substance-abusing women offenders in community
      treatment after parole to address their treatment needs, improve their retention
      in treatment, and reduce the likelihood of recidivism.

PMID- 17544297
TI  - Methamphetamine use by incarcerated women: comorbid mood and anxiety problems.
AB  - OBJECTIVE: Methamphetamine's (MA) impact on psychiatric functioning is not well
      understood, especially among women. Efforts to understand MA's impact are
      complicated by the use of other drugs. The purpose of this study is to untangle
      the relative contributions of MA versus other drugs on psychiatric symptoms.
      METHOD: Incarcerated women (N = 100) completed diagnostic interviews and a
      symptom measure to establish psychiatric status. FINDINGS: Nearly all women (83%)
      had lifetime dependence on > or =1 drugs. The most common drug of dependence was
      MA (67%), followed by alcohol (32%), cannabis (19%), and cocaine (15%). Over half
      met lifetime criteria for an affective disorder (53%), and nearly half (46%) met
      lifetime criteria for an anxiety disorder. Lifetime dependence on MA and a
      nonstimulant drug was related to current psychiatric symptoms and lifetime mood
      and anxiety disorder. Lifetime mood and anxiety disorders were generally
      unrelated to recent MA use. CONCLUSION: Findings highlight the impact of MA use
      on psychiatric presentation among women. Results suggest that MA impacts
      psychiatric symptoms independent of lifetime psychiatric diagnoses. Of note was
      the high incidence of drug dependence and mood and anxiety disorders among this
      sample of incarcerated women from a rural state. Findings imply important
      treatment implications for women in prison settings.

PMID- 17544298
TI  - Psychiatric distress in incarcerated women with recent cocaine and alcohol abuse.
AB  - PURPOSE: Women frequently abuse cocaine and alcohol before incarceration.
      Research indicates that women in criminal justice settings also suffer high rates
      of psychiatric distress. This study aimed to determine how preincarceration abuse
      of alcohol and cocaine affected current psychiatric distress among female jail
      detainees held for 10-14 days. METHODS: A probability sample of women in a large
      urban jail (n = 469) were assessed for use of alcohol and cocaine during the 6
      months before incarceration and for their current psychiatric distress. They were
      grouped based on their level of alcohol consumption and cocaine use: high
      cocaine/high alcohol; high cocaine/low alcohol; low cocaine/high alcohol; and low
      cocaine/low alcohol. Profile analysis was used to examine the relation of
      psychiatric distress, as measured by the Brief Symptom Inventory, to levels of
      recent alcohol and cocaine use. RESULTS: Psychiatric distress is highest (and
      similar) among women in the high cocaine groups, regardless of alcohol use, and
      psychiatric distress is lowest among those who used both substances infrequently.
      Characteristics of psychiatric distress differed based on level of alcohol use,
      but only when cocaine use was low. High alcohol and cocaine use alone and
      together also predict the likelihood of psychiatric distress reaching a
      diagnosable level of severity. CONCLUSIONS: High cocaine, alcohol, or combined
      use is related to higher levels of psychiatric distress among incarcerated women
      in this jail. Women should be screened at the time of incarceration, and women
      who have alcohol and other drug problems should receive treatment that includes
      mental health services.

PMID- 17544299
TI  - Self-consciousness in non-communicative patients.
AB  - The clinical and para-clinical examination of residual self-consciousness in non
      communicative severely brain damaged patients (i.e., coma, vegetative state and
      minimally conscious state) remains exceptionally challenging. Passive
      presentation of the patient's own name and own face are known to be effective
      attention-grabbing stimuli when clinically assessing consciousness at the
      patient's bedside. Event-related potential and functional neuroimaging studies
      using such self-referential stimuli are currently being used to disentangle the
      cognitive hierarchy of self-processing. We here review neuropsychological,
      neuropathological, electrophysiological and neuroimaging studies using the own
      name and own face paradigm obtained in conscious waking, sleep, pharmacological
      coma, pathological coma and related disorders of consciousness. Based on these
      results we discuss what we currently do and do not know about the functional
      significance of the neural network involved in "automatic" and "conscious" self
      referential processing.

PMID- 17544300
TI  - Modelling the magnetic signature of neuronal tissue.
AB  - Neuronal communication in the brain involves electrochemical currents, which
      produce magnetic fields. Stimulus-evoked brain responses lead to changes in these
      fields and can be studied using magneto- and electro-encephalography (MEG/EEG).
      In this paper we model the spatiotemporal distribution of the magnetic field of a
      physiologically idealized but anatomically realistic neuron to assess the
      possibility of using magnetic resonance imaging (MRI) for directly mapping the
      neuronal currents in the human brain. Our results show that the magnetic field
      several centimeters from the centre of the neuron is well approximated by a
      dipole source, but the field close to the neuron is not, a finding particularly
      important for understanding the possible contrast mechanism underlying the use of
      MRI to detect and locate these currents. We discuss the importance of the
      spatiotemporal characteristics of the magnetic field in cortical tissue for
      evaluating and optimizing an experiment based on this mechanism and establish an
      upper bound for the expected MRI signal change due to stimulus-induced cortical
      response. Our simulations show that the expected change of the signal magnitude
      is 1.6% and its phase shift is 1 degrees . An unexpected finding of this work is
      that the cortical orientation with respect to the external magnetic field has
      little effect on the predicted MRI contrast. This encouraging result shows that
      magnetic resonance contrast directly based on the neuronal currents present in
      the cortex is theoretically a feasible imaging technique. MRI contrast generation
      based on neuronal currents depends on the dendritic architecture and we obtained
      high-resolution optical images of cortical tissue to discuss the spatial
      structure of the magnetic field in grey matter.

PMID- 17544301
TI  - Functional MRI detection of bilateral cortical reorganization in the rodent brain
      following peripheral nerve deafferentation.
AB  - Evidence is emerging for significant inter-hemispheric cortical plasticity in
      humans, opening important questions about the significance and mechanism for this
      long range plasticity. In this work, peripheral nerve deafferentation was
      performed on both the rat forepaw and hindpaw and cortical reorganization was
      assessed using functional MRI (fMRI). Sensory stimulation of the forepaw or the
      hindpaw in rats that experienced only partial denervation resulted in activation
      in only the appropriate, contralateral, primary somatosensory cortex (SI).
      However, 2-3 weeks following complete denervation of the rats' forepaw or
      hindpaw, stimulation of the intact paw resulted in fMRI activation of ipsilateral
      as well as contralateral SI. To address whether inter-cortical communication is
      required for this cortical reorganization, the healthy hindpaw SI representation
      was stereotaxically lesioned in rats which had the other hindpaw denervated. No
      fMRI activation was detected in the ipsilateral SI cortex after lesioning of the
      contralateral cortex. These results indicate that extensive inter-hemispheric
      cortical-cortical reorganization can occur in the rodent brain after peripheral
      nerve deafferentation and that cortical-cortical connections play a role in
      mediating this inter-hemispheric cortical reorganization.

PMID- 17544302
TI  - Phylogeny of the snailfishes (Teleostei: Liparidae) based on molecular and
      morphological data.
AB  - Liparidae (snailfishes) is one of the most diverse and abundant fish families in
      polar and deep-sea habitats. However, the evolution of this family is poorly
      known because of the rarity of many species and difficulties in scoring
      morphological characters. We perform phylogenetic analyses of Liparidae using
      sequences from two mtDNA genes, 16S (585 bp) and cytochrome b (426 bp), and 84
      morphological characters from 24 species of Liparidae and 4 species of
      Cyclopteridae (outgroup). The present study confirms earlier hypotheses that the
      shallow-water genera, such as Liparis and Crystallichthys, occupy basal positions
      and that deep-water genera, such as Careproctus, Elassodiscus, Rhinoliparis,
      Paraliparis, Rhodichthys and Psednos, are increasingly derived. The later two
      genera form a terminal clade which does not include Paraliparis. The topology
      shows that the family has undergone a reductive type of evolution, with a gradual
      loss of characters (e.g. sucking disc/pelvic fins, pseudobranchial filaments,
      skin spinules). Nectoliparis, which had previously been placed either as the
      basal most genus or among the most derived genera, are found to occupy the most
      basal position among the taxa analyzed. This result indicates that the sucking
      disc has been lost at least twice during the evolution of the Liparidae. The
      basal position of Nectoliparis is supported by its plesiomorphic otolith
      morphology, whereas an advanced overgrown otolith ostium, unique among teleosts,
      is found to be apomorphic for a clade containing the derived genera: Paraliparis,
      Psednos, Rhinoliparis and Rhodichthys. We also identify the presence of probable
      nuclear inserts of mitochondrial DNA (Numts) in three species of Careproctus and
      in Elassodiscus caudatus.

PMID- 17544303
TI  - Learning and memory deficits in mice lacking protease activated receptor-1.
AB  - The roles of serine proteases and protease activated receptors have been
      extensively studied in coagulation, wound healing, inflammation, and
      neurodegeneration. More recently, serine proteases have been suggested to
      influence synaptic plasticity. In this context, we examined the role of protease
      activated receptor 1 (PAR1), which is activated following proteolytic cleavage by
      thrombin and plasmin, in emotionally motivated learning. We were particularly
      interested in PAR1 because its activation enhances the function of NMDA
      receptors, which are required for some forms of synaptic plasticity. We examined
      several baseline behavioral measures, including locomotor activity, expression of
      anxiety-like behavior, motor task acquisition, nociceptive responses, and startle
      responses in C57Bl/6 mice in which the PAR1 receptor has been genetically
      deleted. In addition, we evaluated learning and memory in these mice using two
      memory tasks, passive avoidance and cued fear-conditioning. Whereas locomotion,
      pain response, startle, and measures of baseline anxiety were largely unaffected
      by PAR1 removal, PAR1-/- animals showed significant deficits in a passive
      avoidance task and in cued fear conditioning. These data suggest that PAR1 may
      play an important role in emotionally motivated learning.

PMID- 17544304
TI  - Exploring ligand recognition and ion flow in comparative models of the human GABA
      type A receptor.
AB  - We present two comparative models of the GABA(A) receptor. Model 1 is based on
      the 4-A resolution structure of the nicotinic acetylcholine receptor from Torpedo
      marmorata and represents the unliganded receptor. Two agonists, GABA and
      muscimol, two benzodiazepines, flunitrazepam and alprazolam, together with the
      general anaesthetic halothane, have been docked to this model. The ion flow is
      also explored in model 1 by evaluating the interaction energy of a chloride ion
      as it traverses the extracellular, transmembrane and intracellular domains of the
      protein. Model 2 differs from model 1 only in the extracellular domain and
      represents the liganded receptor. Comparison between the two models not only
      allows us to explore commonalities and differences with comparative models of the
      nicotinic acetylcholine receptor, but also suggests possible protein sub-domain
      interactions with the GABA(A) receptor not previously addressed.

PMID- 17544305
TI  - The effect of alpha- and beta-adrenergic blockade on daily rhythms of body
      temperature, urine production, and urinary 6-sulfatoxymelatonin of social voles
      Microtus socialis.
AB  - To examine the effect of adrenergic blockade on daily rhythms of rectal body
      temperature (T(b)), urine production rate, and melatonin (MEL; measured as
      urinary 6-sulfatoxymelatonin; 6-SMT), social voles Microtus socialis received a
      single intra-peritoneal injection of either prazosin (PRAZ, 1 mg/kg) or
      propranolol (PROP, 4.5 mg/kg); alpha- and beta-adrenergic blocking agents
      respectively, 1 h prior to scotophase onset (light/dark, 12L:12D; lights on 07:00
      h). Both blockers caused significant decrease in T(b) values mainly during
      scotophase. Nocturnal urine production rates were higher for M. socialis treated
      with the drugs compared with controls. Overall, urine production rates were
      systematically higher in PROP-voles over the 24 h period when compared with PRAZ
      voles; however these differences were not statistically significant.
      Interestingly, PROP caused significant elevation in urinary 6-SMT at the second
      half of the dark phase, whereas PRAZ had no effects. These data suggest that the
      mechanisms regulating MEL synthesis and thermoregulatory responses in M. socialis
      are different from those described in other rodents' species. Importantly, the
      data also suggest that the beta-blockade-induced elevation in MEL levels may be
      directly associated with increased urination in M. socialis.

PMID- 17544306
TI  - Endothelium-dependent and -independent relaxation in the forelimb and hindlimb
      vasculatures of swine.
AB  - Limb differences in endothelial function exist between arm and leg vasculatures
      of humans. The current investigation tested the hypothesis that forelimb and
      hindlimb vasorelaxation are similar in the absence of limb differences in blood
      pressure. Conduit arteries (brachials/femorals) and second order arterioles were
      harvested from 22 miniature Yucatan swine. In vitro assessment of vasorelaxation
      was determined by administering increasing doses of bradykinin (BK),
      acetylcholine (ACh), and sodium nitroprusside (SNP). The role of the nitric oxide
      synthase (NOS) and cyclooxygenase (COX) pathways was assessed in conduit arteries
      but not resistance arterioles through L-NAME (300 microM) and INDO (5 microM)
      incubation, respectively. The relaxation responses to BK and ACh were similar in
      brachial and femoral arteries. SNP relaxation response was greater in the
      brachial compared to femoral arteries. There were also no significant differences
      in the relaxation responses of second order arterioles of the forelimb and
      hindlimb to BK, ACh, and SNP. Incubation of conduit arterial rings in L-NAME
      produced a greater reduction in BK and ACh relaxation in the brachial
      (approximately 25%) compared to femoral (approximately 13%) arterial rings. The
      current results of this investigation suggest that the forelimb and hindlimb
      vasculatures of swine have relatively similar vasorelaxation responses to both
      endothelium-dependent and -independent vasodilators.

PMID- 17544307
TI  - Reductive inactivation of yeast glutathione reductase by Fe(II) and NADPH.
AB  - Glutathione reductase (GR) carries out the enzymatic reduction of glutathione
      disulfide (GSSG) to its reduced form (GSH) at the expense of the reducing power
      of NADPH. Previous studies have shown that GR from several species is
      progressively inactivated in the presence of NADPH, but that the mechanism of
      inactivation (especially in the presence of metals) has not been fully
      elucidated. We have investigated the involvement of iron ions in the inactivation
      of yeast (Saccharomyces cerevisiae) GR in the presence of NADPH. Even in the
      absence of added iron, inactivation of GR was partly blocked by the iron
      chelators, deferoxamine and ortho-phenanthroline, suggesting the involvement of
      trace amounts of contaminating iron in the mechanism of inhibition. Exogenously
      added antioxidants including ethanol, dimethylsulfoxide and 2-deoxyribose did not
      protect GR against NADPH-induced inactivation, whilst addition of exogenous
      Fe(II) (but not Fe(III)) potentiated the inactivation. Moreover, removal of
      oxygen from the medium led to increased inhibition of GR, whereas pre-incubation
      of the Fe(II)-containing medium for 30 min under normoxic conditions prior to the
      addition of GR abolished the enzyme inactivation by NADPH. Under these pre
      incubation conditions, Fe(II) is fully oxidized to Fe(III) within 1 min.
      Furthermore, GR that had been previously inactivated in the presence of Fe(II)
      plus NADPH could be partially reactivated by treatment with ortho-phenanthroline
      and deferoxamine. In contrast, Fe(III) had no effect on GR reactivation.
      Together, these results indicate that yeast GR is inactivated by a reductive
      mechanism mediated by NADPH and Fe(II). According to this mechanism, GR is
      diverted from its normal redox cycling by the generation of an inactive reduced
      enzyme form in which both the FAD and thiol groups at the active site are likely
      in a reduced state.

PMID- 17544308
TI  - Susceptibility of mammalian deoxyribonucleases I (DNases I) to proteolysis by
      proteases and its relationships to tissue distribution: biochemical and molecular
      analysis of equine DNase I.
AB  - Equine (Equus caballus) deoxyribonuclease I (DNase I) was purified from the
      parotid gland, and its 1295-bp cDNA was cloned. The mature equine DNase I protein
      consisted of 260 amino acid residues. The enzymatic properties and structural
      aspects of the equine enzyme were closely similar to those of other mammalian
      DNases I. Mammalian DNases I are classified into three types--pancreatic, parotid
      and pancreatic-parotid-based on their tissue distribution; as equine DNase I
      showed the highest activity in the parotid gland, it was confirmed to be of the
      parotid-type. Comparison of the susceptibility of mammalian DNases I to
      proteolysis by proteases demonstrated a marked correlation between tissue
      distribution and sensitivity/resistance to proteolysis; pancreatic-type DNase I
      shared properties of resistance to proteolysis by trypsin and chymotrypsin,
      whereas parotid-type DNase I did not. In contrast, pancreatic-parotid-type DNase
      I exhibited resistance to proteolysis by pepsin, whereas the other enzyme types
      did not. However, site-directed mutagenesis analysis revealed that only a single
      amino acid substitution could not account for acquisition of proteolysis
      resistance in the mammalian DNase I family during the course of molecular
      evolution. These properties are compatible with adaptation of mammalian DNases I
      for maintaining their activity in vivo.

PMID- 17544309
TI  - Cloning of the glucocorticoid receptor (GR) in gilthead seabream (Sparus aurata).
      Differential expression of GR and immune genes in gilthead seabream after an
      immune challenge.
AB  - In order to determine the cortisol response after an immune challenge in the
      gilthead seabream (Sparus aurata), a cortisol receptor (GR) was cloned, sequenced
      and its expression determined after lipopolysaccharide (LPS) treatment. To clone
      the gilthead seabream GR (sbGR), consecutive PCR amplifications and screening of
      a pituitary cDNA library were performed. We obtained a clone of 4586 bp encoding
      a 784aa protein. Northern blot analysis from head kidney, heart and intestine
      revealed that the full length sbGR mRNA was approximately 6.5 Kb. A LPS
      treatment, used as an acute stress model, was employed to characterise the
      expression of sbGR and some selected genes involved in the immune response (IL
      1beta, TNF-alpha, Mx protein, cathepsin D and PPAR-gamma). All genes were
      expressed in all tissues examined and responses were tissue and time dependent
      revealing differential gene expression profiles after LPS administration.
      Furthermore, analysis of plasma cortisol levels after LPS injection, showed an
      acute response to inflammatory stress with a significant increase two and six h
      after injection, recovering to basal levels 12 h post-stress in all LPS
      concentrations tested.

PMID- 17544310
TI  - Long-term intra-articular administration of recombinant human N
      acetylgalactosamine-4-sulfatase in feline mucopolysaccharidosis VI.
AB  - Degenerative joint disease (DJD) is one aspect of mucopolysaccharidosis VI (MPS
      VI) pathology that has proven resistant to systemic enzyme replacement therapy
      (ERT). In this study the effect of repeated intra-articular injections (IA INJ)
      of recombinant human acetylgalactosamine-4-sulfatase (rh4S) on DJD was examined.
      Four MPS VI cats received i.v. ERT weekly from birth plus IA INJ (0 or 500 microg
      of rh4S per joint; monthly or every three months) while three MPS VI cats
      received IA INJ only. After 10 months, shoulders, elbows and knees were compared.
      Taken individually, an improvement in joint appearance was observed between the
      joints that received rh4S monthly or every three months compared with the
      contralateral joints treated with buffer or at lower frequency. Within articular
      cartilage of joints treated more frequently, the depth of clearance of lysosomal
      storage tended to be greater and uronic acid content was reduced reflecting the
      removal of glycosaminoglycans. Synovium in treated joints also showed less
      storage. No abnormal clinical signs were observed after the IA INJ and negligible
      antibody titres were measured throughout the study. No clear benefit was observed
      by combining IA INJ with weekly ERT and the most significant improvement in joint
      appearance resulted from increased IA INJ frequency. These data support the view
      that intra-articular therapy may be a good option for preventing the development
      of the severe articular pathology in MPS VI.

PMID- 17544311
TI  - Presence of virulence and fitness gene modules of enterohemorrhagic Escherichia
      coli in atypical enteropathogenic Escherichia coli O26.
AB  - Enterohemorrhagic Escherichia coli (EHEC) strains of serogroup O26 cause
      hemolytic-uremic syndrome (HUS) whereas atypical enteropathogenic E. coli (aEPEC)
      O26 typically cause uncomplicated diarrhea but have been also isolated from HUS
      patients. To gain insight into the virulence of aEPEC O26, we compared the
      presence of O island (OI) 122, which is associated with enhanced virulence in
      EHEC strains, among aEPEC O26 and EHEC O26 clinical isolates. We also tested
      these strains for the high pathogenicity island (HPI) which is a fitness island.
      All 20 aEPEC O26 and 20 EHEC O26 investigated contained virulence genes located
      within OI-122 (efa1/lifA, nleB, nleE, ent). In both aEPEC O26 and EHEC O26, OI
      122 was linked to the locus for enterocyte effacement, forming a mosaic island
      which was integrated in pheU. Moreover, strains of these two pathotypes shared a
      conserved HPI. These data support a close relatedness between aEPEC O26 and EHEC
      O26 and have evolutionary implications. The presence of OI-122 in aEPEC O26 might
      contribute to their pathogenic potential.

PMID- 17544312
TI  - [Prevention and management of the conflict patient-doctor].
AB  - A surgeon's daily practice evolves according to techniques, but also according to
      a legal and associative environment. The patient is becoming a health consumer,
      demanding and informed, legitimately exacting security and transparency, but also
      compensation in the event of accidental injury. The constraints that weigh upon
      this profession are growing heavier: knowledge and respect of laws, ordinances
      and regulations are becoming essential and law suits more and more frequent. Ever
      present in surgery, risk evaluation and assessing the risk-benefit ratio for the
      patient must be clearly stated by the practitioner and his team, despite the
      inherent difficulties in sharing information. A classification of surgical risk
      facilitates an approach to the definitions of a fault, medical accident,
      iatrogenic condition or undesirable event. This is a fundamental concept, since
      precise criteria apply to a fault in the legal sense, whereas no normative
      definition exists for a medical fault. Prevention of conflict requires the
      implementation of collective steps aimed at ensuring security in a complex
      system, confidence between the surgeon and his patient based on appropriate
      information and strict adherence to current regulations. In the event of
      complications, difficult after-effects, objectively unsatisfactory results or
      those perceived as such by the patient, post-operative follow-up must face these
      difficulties squarely with transparency and responsibility. Following a legal
      summons involving the responsibility of the practitioner, management of the
      conflict between the physician and the patient requires solid preparation of the
      medical file and his active participation in the judicial expertise so as to best
      inform the judge.

PMID- 17544313
TI  - [Fetal toxicity of angiotensin-II-receptor inhibitors. Case report].
AB  - The fetal toxicity of angiotensin-converting enzyme inhibitors (ACEI) is now well
      known. Sartans which are angiotensin II inhibitors, are supposed to have the same
      side effects on the fetus as ACEI because of their similar mechanism of action.
      This is supported by experimental and clinical data. Clinical presentation of
      fetal exposition to sartans varies from transient oligamnios to permanent renal
      failure, potentially complicated by Potter syndrome. According to previously
      reported cases, we report a case of transitory fetal oliguria secondary to the
      exposure to an angiotensin-II-receptor inhibitor (valsartan) between 19 and 21
      weeks' gestation. We discuss the management of pregnancies exposed to angiotensin
      II inhibitors.

PMID- 17544314
TI  - [Fetal pulse oxymetry].
AB  - Labor is monitored to avoid per partum asphyxia and its consequences.
      Cardiotocography enables asphyxia detection but carries unuseful cesarean
      sections. When cardiotocography is not reassuring, fetal pulse oxymetry makes it
      possible to reduce cesarean section rate for non-reassuring fetal status.
      Nevertheless, there is an increased number of cesarean sections for dystocia that
      could be due to the presence of the oxygen sensor itself. A global reduction is
      mainly observed when oxymetry is associated with fetal blood sampling for pH
      measurement. In this case, oxymetry also makes it possible to reduce the number
      of necessary samplings.

PMID- 17544315
TI  - Intensification of esterification of acids for synthesis of biodiesel using
      acoustic and hydrodynamic cavitation.
AB  - Cavitation results in conditions of turbulence and liquid circulation in the
      reactor which can aid in eliminating mass transfer resistances. The present work
      illustrates the use of cavitation for intensification of biodiesel synthesis
      (esterification) reaction, which is mass transfer limited reaction considering
      the immiscible nature of the reactants, i.e., fatty acids and alcohol.
      Esterification of fatty acid (FA) odour cut (C(8)-C(10)) with methanol in the
      presence of concentrated H(2)SO(4) as a catalyst has been studied in hydrodynamic
      cavitation reactor as well as in the sonochemical reactor. The different reaction
      operating parameters such as molar ratio of acid to alcohol, catalyst quantity
      have been optimized under acoustic as well as hydrodynamic cavitating conditions
      in addition to the optimization of the geometry of the orifice plate in the case
      of hydrodynamic cavitation reactors. Few experiments have also been carried out
      with other acid (lower and higher)/methanol combination viz. caprylic acid and
      capric acids with methanol with an aim of investigating the efficacy of
      cavitation for giving the desired yields and also to quantify the degree of
      process intensification that can be achieved using the same. It has been observed
      that ambient operating conditions of temperature and pressure and reaction times
      of <3h, for all the different combinations of acid (lower and higher)/methanol
      studied in the present work, was sufficient for giving >90% conversion (mol%).
      This clearly establishes the efficacy of cavitation as an excellent way to
      achieve process intensification of the biodiesel synthesis process.

PMID- 17544316
TI  - Effect of reactor's positions on polymerization and degradation in an ultrasonic
      field.
AB  - Ultrasonic generators are used as emulsifiers and efficient alternative
      initiators in polymerization processes. In this study, the effects of reactor's
      position on the emulsion polymerization of styrene under indirect ultrasonic
      irradiation were investigated, along with the effects of reactor's position on
      chemical and physical degradation. Both polymer yield and molecular weight were
      influenced by the position of the reactor. The ultrasonic irradiation could be
      divided into three stages, and the molecular weight of the polymer was influenced
      by polymerization and degradation processes. It was found that the extent of
      radical generation estimated by KI oxidation dosimetry and the shock wave index
      obtained from studies of degradation of standard polymer were useful for
      controlling the characteristics of the polymer generated.

PMID- 17544317
TI  - Estimating CHD prevalence by small area: integrating information from health
      surveys and area mortality.
AB  - The risk of coronary heart disease (CHD) is strongly linked both to deprivation
      and ethnicity and so prevalence will vary considerably between areas. Variations
      in prevalence are important in assessing health care needs and how far CHD
      service provision and surgical intervention rates match need. This paper uses a
      regression model of prevalence rates by age, sex, region and ethnicity from the
      1999 and 2003 Health Surveys for England to estimate CHD prevalence for 354
      English local authority areas. To allow for the impact of social factors on
      prevalence, survey information on the deprivation quintile in the respondents'
      micro-area of residence is also used. Allowance is also made for area CHD
      mortality rates (obtained from aggregated vital statistics data) which are
      positively correlated with, and hence a proxy for, CHD prevalence rates. An
      application involves assessment of surgical intervention rates in relation to
      prevalence at the level of 28 Strategic Health Authorities.

PMID- 17544318
TI  - Ghrelin: a new peptide regulating growth hormone release and food intake.
AB  - Ghrelin, identified as an endogenous ligand for the growth hormone secretagogue
      receptor, is a 28 amino acid peptide hormone possessing an unusual octanoyl group
      on the serine in position 3, crucial for its biological activity. Ghrelin is
      predominantly produced by the stomach but also by many other tissues such as
      pituitary, hypothalamus, duodenum, jejunum, ileum, colon, lung, heart, pancreas,
      kidney, and testis. In addition to stimulation of GH release, ghrelin stimulates
      appetite and food intake, enhancing fat mass deposition and weight gain. Besides
      these main actions, ghrelin regulates gastric motility and acid secretion, exerts
      cardiovascular and anti-inflammatory effects, modulates cell proliferation and
      influences endocrine and exocrine pancreatic secretion, as well as glucose and
      lipid metabolism. Therefore, ghrelin agonists and antagonists might be valuable
      for some clinical aspects.

PMID- 17544319
TI  - Suppressive effects of the anti-oxidant N-acetylcysteine on the anti-malarial
      activity of artesunate.
AB  - The anti-oxidant drug N-acetylcysteine (NAC) has been proposed as adjunctive
      treatment in severe falciparum malaria. However, this might inhibit the anti
      malarial drug action of the artemisinins, which are thought to exert their
      parasitocidal action through oxidative damage. We studied the interaction between
      NAC and artesunate as well as quinine in an in vitro drug sensitivity assay.
      Combination with NAC reduced the parasitocidal effect of artesunate only within
      the first 6 h of incubation, whereas no interaction was observed with quinine.
      Pre-incubation of P. falciparum with NAC resulted in a similar inhibitory effect
      on the anti-malarial activity of artesunate, whereas no inhibition was observed
      when NAC was added 2 h after parasite exposure to artesunate. Assessment of
      parasite maturation inhibition by the standard Giemsa's staining was in
      accordance with the use of a vital staining. The results herein caution the use
      of adjunctive treatment for malaria infection. Combination of antagonistic drugs
      may lead to adverse effects.

PMID- 17544320
TI  - Amino-imino tautomerization reaction of the 4-aminopyrimidine/acetic acid system.
AB  - The amino-imino tautomerization of the 4-aminopyrimidine (4APM)/acetic acid
      (AcOH) system through dual hydrogen bonding in n-hexane at room temperature was
      investigated using UV absorption and fluorescence spectroscopies, fluorescence
      time-profile measurements, and molecular orbital calculations, with those of the
      imino-model compound of 3-methyl-4(1H)-pyrimidinimine (3M4PMI). From the
      experimental results, it was confirmed that the imino-tautomer was formed in the
      first excited singlet state (S1) state through the double-proton transfer of the
      dual hydrogen-bonded complex of 4APM with AcOH. The fluorescences of the free
      4APM monomer (band maximum at 353nm), imino-tautomer (at 414nm), and 3M4PMI
      monomer (at 437nm) exhibit the single-exponential decays of 98, 73, and 19ps time
      constants, respectively. The shorter decay time of the imino-tautomer
      fluorescence compared with the free monomer one is suggestive of the low
      activation energy process in the S1 state. From the result of the shortest decay
      time of the 3M4PMI fluorescence, it can be deduced that 3M4PMI has a non-planar
      structure in the S1 state. The theoretical calculations on the S0 and S1 state
      double-proton transfer for the 4APM/AcOH dual hydrogen-bonded system were
      performed with the use of formic acid (FoOH) in place of AcOH for the sake of
      simplicity. Only one peak of transition state was resolved in the S0 and S1
      states. The energy barrier for the S1 state double-proton transfer of the
      4APM/FoOH complex-->3H-4(1H)-pyrimidinimine/FoOH tautomer was estimated to be
      approximately 2kJmol(-1) using the CIS/6-31G(d) methods. On the other hand, the
      energy barrier for the S0 state reverse proton transfer of the 3H-4(1H)
      pyrimidinimine/FoOH tautomer-->4APM/FoOH complex was estimated to be almost zero
      kJmol(-1) at B3LYP/6-31G(d) level.

PMID- 17544321
TI  - Tone burst-galvanic ratio of vestibular evoked myogenic potential amplitudes: a
      new parameter of vestibular evoked myogenic potential?
AB  - OBJECTIVE: To clarify whether the ratio of tone burst vestibular evoked myogenic
      potential (VEMP) amplitude to galvanic (electric) VEMP amplitude can be a useful
      indicator of peripheral vestibular disorders, especially labyrinthine disorders.
      METHODS: Twelve healthy volunteers and 12 patients with endolymphatic hydrops
      (EH) were enrolled in this study. VEMP was recorded using 500 Hz short tone
      bursts (135dBSPL, rise/fall time 1 ms, plateau time 2 ms) and galvanic
      stimulation (3 mA, 1 ms). Amplitudes of p13-n23 (tone burst) and p13g-n23g
      (galvanic) were corrected using background muscle activity. We defined the ratio
      of the corrected amplitude of p13-n23 to the corrected amplitude of p13g-n23g as
      TGratio. RESULTS: The mean+/-SD of logarithmic value of TGratio (LTGratio) of
      healthy volunteers was 0.34+/-0.12. LTGratios in patients were 0.002+/-0.24 on
      the affected side and 0.34+/-0.14 on the unaffected side. LTGratio on the
      affected side of patients was significantly smaller than the ratio on the
      unaffected side and the ratio of healthy volunteers. Among the 12 patients with
      EH, 8 patients (66%) had significantly decreased LTGratio (smaller than mean-2SD
      of healthy volunteers). CONCLUSIONS: Patients with EH had decreased ratio of tone
      burst VEMP amplitude to galvanic VEMP amplitude. SIGNIFICANCE: TGratio (or
      LTGratio) could be a new promising parameter of VEMP as it can be calculated from
      results of one side.

PMID- 17544322
TI  - Comparison of novel computer detectors and human performance for spike detection
      in intracranial EEG.
AB  - OBJECTIVE: Interictal spikes in intracranial EEG (iEEG) may correlate with
      epileptogenic cortex, but review of interictal iEEG is labor intensive. Accurate
      automated spike detectors are necessary for understanding the role of spikes in
      epileptogenesis. METHODS: The sensitivity, accuracy and reproducibility of three
      automated iEEG spike detectors were compared against two human EEG readers using
      iEEG segments from eight patients. A consensus set of detections was generated
      for detector calibration. Spike verification was calculated after both human EEG
      readers independently reviewed all detections. RESULTS: Humans and two of the
      three automated detectors demonstrated comparable accuracy. In four patients,
      automated spike detection sensitivity was >70% and accuracy was >50%. In the
      remaining four patients, EEG background morphology resulted in poorer
      performance. Blinded human verification accuracy was 76.7+/-6.6% for computer
      detected spikes, and 84.5+/-4.1% for human-detected spikes. CONCLUSIONS:
      Automated iEEG spike detectors perform comparably to humans, but sensitivity and
      accuracy are patient dependent. Humans verified the majority of computer-detected
      spikes. SIGNIFICANCE: In some patients automated detectors may be used for
      mapping spike occurrences in epileptic networks. This may reveal associations
      between spike distribution, seizure onset, and pathology.

PMID- 17544323
TI  - Diagnostic standards for dopaminergic augmentation of restless legs syndrome:
      report from a World Association of Sleep Medicine-International Restless Legs
      Syndrome Study Group consensus conference at the Max Planck Institute.
AB  - OBJECTIVES: Augmentation of symptom severity is the main complication of
      dopaminergic treatment of restless legs syndrome (RLS). The current article
      reports on the considerations of augmentation that were made during a European
      Restless Legs Syndrome Study Group (EURLSSG)-sponsored Consensus Conference in
      April 2006 at the Max Planck Institute (MPI) in Munich, Germany, the conclusions
      of which were endorsed by the International RLS Study Group (IRLSSG) and the
      World Association of Sleep Medicine (WASM). The Consensus Conference sought to
      develop a better understanding of augmentation and generate a better operational
      definition for its clinical identification. DESIGN AND METHODS: Current concepts
      of the pathophysiology, clinical features, and therapy of RLS augmentation were
      evaluated by subgroups who presented a summary of their findings for general
      consideration and discussion. Recent data indicating sensitivity and specificity
      of augmentation features for identification of augmentation were also evaluated.
      The diagnostic criteria of augmentation developed at the National Institutes of
      Health (NIH) conference in 2002 were reviewed in light of current data and
      theoretical understanding of augmentation. The diagnostic value and criteria for
      each of the accepted features of augmentation were considered by the group. A
      consensus was then developed for a revised statement of the diagnostic criteria
      for augmentation. RESULTS: Five major diagnostic features of augmentation were
      identified: usual time of RLS symptom onset each day, number of body parts with
      RLS symptoms, latency to symptoms at rest, severity of the symptoms when they
      occur, and effects of dopaminergic medication on symptoms. The quantitative data
      available relating the time of RLS onset and the presence of other features
      indicated optimal augmentation criteria of either a 4-h advance in usual starting
      time for RLS symptoms or a combination of the occurrence of other features. A
      paradoxical response to changes in medication dose also indicates augmentation.
      Clinical significance of augmentation is defined. CONCLUSION: The Consensus
      Conference agreed upon new operational criteria for the clinical diagnosis of RLS
      augmentation: the MPI diagnostic criteria for augmentation. Areas needing further
      consideration for validating these criteria and for understanding the underlying
      biology of RLS augmentation are indicated.

PMID- 17544324
TI  - Neutralizing and cross-reactive antibodies against enterobacterial
      lipopolysaccharide.
AB  - Lipopolysaccharide (LPS, endotoxin) elicits an immune reaction which is
      responsible for many of the harmful effects seen in septic shock patients. The
      eradication of bacteria by antibiotics is insufficient to resolve the pathology
      due to the lack of LPS neutralization. LPS-neutralizing antibodies have been
      described; however, these were specific for the serotype of the infecting
      bacteria and thus not useful for the treatment of septic shock patients.
      Structural analyses revealed that the LPS structures of Escherichia coli and
      Salmonella are structurally conserved in the inner core region. Using whole LPS
      and a panel of neoglycoconjugates containing purified LPS oligosaccharides, which
      we have obtained from all E. coli core types (K-12, R1, R2, R3 and R4),
      Salmonella enterica, and the mutant strain E. coli J-5, we have identified an
      epitope which is bound with high affinity by the monoclonal antibody WN1 222-5,
      which has been shown previously shown to be cross-reactive against a large
      collection of blood, fecal, and urinary isolates of E. coli, S. enterica, some
      Citrobacter, independently of the serotype [Di Padova, F.E., Brade, H., Barclay,
      G.R., Poxton, I.R., Liehl, E., Schuetze, E., Kocher, H.P., Ramsay, G., Schreier,
      M.H., McClelland, D.B., Rietschel, E.T., 1993. A broadly cross-protective
      monoclonal antibody binding to Escherichia coli and Salmonella
      lipopolysaccharides. Infect. Immun. 61, 3863-3872]. Importantly, WN1 222-5 was
      protective in various models of endotoxic shock. The minimal structural element
      necessary for high-affinity binding consists of R(1)-alpha-d-Glcp-(1-->3)-[l
      alpha-d-Hepp-(1-->7)]-l-alpha-d-Hepp 4P-(1-->3)-R(2) (R(1), R(2)=additional
      sugars of LPS) in which the side-chain heptose and the 4-phosphate on the
      branched heptose are the main determinants of the epitope. Additional sugars of
      the outer core (R(1)) enhance the affinity, whereas loss of an intact Kdo region
      and/or lipid A (R(2)) prevent binding. The identification of the epitope provides
      the structural basis for the rational development of a potential vaccine against
      E. coli LPS.

PMID- 17544325
TI  - Jump-landing direction influences dynamic postural stability scores.
AB  - The purpose of this investigation was to determine dynamic postural stability
      differences among forward, diagonal, and lateral single leg-hop-stabilization
      protocols in healthy subjects. A one-within repeated measures design was used to
      determine the effects of jump direction on dynamic postural stability during
      landing. Subjects were required to perform a two-legged forward, diagonal, and
      lateral jump to a height equivalent to 50% of their maximum vertical leap, land
      on a single leg and balance for three seconds. Twenty-six subjects [10 males
      (22+/-3.9 years of age, 70.9+/-7.6kg, and 176.8+/-6.5cm) and 16 females (20.6+/
      .5 years of age, 65.6+/-9.1kg, and 166.4+/-5.9cm)] volunteered to participate in
      this investigation. Dynamic postural stability indices for the
      anterior/posterior, medial/lateral, and vertical planes were collected during
      jump-landing trials of each direction. The results of the investigation show that
      medial/lateral and vertical dynamic postural stability were significantly
      affected by the direction of the jump. More specifically, lateral and diagonal
      jump-landings produce increased medial/lateral stability index (MLSI) scores and
      forward jump-landings produce increased vertical stability index (VSI) scores.
      The results suggest that in a healthy population, jump protocol direction will
      statistically affect dynamic postural stability in the frontal and vertical
      planes. These alterations could be exacerbated in individuals with lower
      extremity impairments and further research is warranted.

PMID- 17544326
TI  - Reconstruction accuracy in underwater three-dimensional kinematic analysis.
AB  - Accuracy of kinematic data is of decisive importance in motion analysis
      particularly when they are to be used for the calculation of kinetic parameters,
      like the propulsive forces in swimming. The present study investigated the
      accuracy of underwater three-dimensional (3-D) kinematic analysis using periscope
      systems and calibration volumes with different size. Two analogue cameras (60Hz)
      were used to record the images, along with two stationary periscope systems for
      the underwater recordings. The calibration of the recording space was performed
      using two different-sized calibration frames. The reconstruction accuracy was
      determined in static and dynamic conditions, both under water and out of the
      water. In static conditions, the reconstruction accuracy was determined by
      calculating the root mean square (RMS) error for the reconstruction of eight
      validation points on the calibration frames, and in dynamic conditions it was
      determined by the percentage of RMS error of the reconstructed length of a moving
      rod. The results revealed that in static conditions the RMS error was greater
      during underwater analysis, due to refraction, and it was increased particularly
      in the longitudinal axis as the dimensions of the calibration volume were
      increased. The reconstruction errors observed during underwater recordings with
      both calibration volumes (transverse axis, 1.61-2.35mm; longitudinal, 2.99
      4.64mm; vertical, 2.83-2.59mm) may be considered suitable for three-dimensional
      kinematic analysis of swimming.

PMID- 17544327
TI  - Performance and anthropometric characteristics of prospective elite junior
      Australian footballers: a case study in one junior team.
AB  - The aim of the study was to compare anthropometric and physical performance data
      of players who were selected for a Victorian elite junior U18 Australian rules
      football squad. Prior to the selection of the final training squad, 54 players
      were assessed using a battery of standard anthropometric and physical performance
      tests. Multivariate analysis (MANOVA) showed significant (p<0.05) differences
      between selected and non-selected players when height, mass, 20-m sprint, agility
      and vertical jump height were considered collectively. Univariate analysis
      revealed that the vertical jump was the only significant (p<0.05) individual test
      and a near significant trend (p=0.07) for height differentiating between selected
      and non-selected players with medium effect sizes for all other tests except
      endurance. In this elite junior football squad, physical characteristics can be
      observed that discriminate between players selected and non-selected, and
      demonstrates the value of physical fitness testing within the talent
      identification process of junior (16-18 years) players for squad and/or team
      selection. Based on MANOVA results, the findings from this study suggest team
      selection appeared to be related to a generally higher performance across the
      range of tests. Further, age was not a confounding variable as players selected
      tended to be younger than those non-selected. These findings reflect the general
      consensus that, in state-based junior competition, there is evidence of promoting
      overall player development, selecting those who are generally able to fulfil a
      range of positions and selecting players on their potential.

PMID- 17544328
TI  - The hydration ability of three commercially available sports drinks and water.
AB  - This paper compares the hydration ability of three commercially-available sports
      drinks with water under conditions of rest and exercise, using a deuterium
      dilution technique. For the rest group, 0.05g/kg of body weight of deuterium,
      contained in gelatine capsules, was ingested with one of the test solutions and
      saliva samples were collected every five minutes for an hour while the subject
      remained seated. The deuterium was administered as above for the exercise group
      but sample collection was during one hour of exercise on a treadmill at 55% of
      the subject's maximum heart rate. The enrichment data for each subject were
      mathematically modelled to describe the kinetics of hydration and the parameters
      obtained were compared across drinks using a basic Anova. At rest, significant
      differences were found for t(1), t(1/2), and the percent of drink absorbed at
      t(1). The differences between drinks were not significant for t(2) or the maximum
      absorption rate. For the exercise group, the only significant difference was
      found between water and the sports drinks at t(1). Therefore, we conclude that
      labelling with a deuterium tracer is a good measure of the relative rate ingested
      fluids are absorbed by the body. Because of the lack of differences found at
      t(2), which is indicative of the 100% absorption time, both at rest and during
      exercise, it may be speculated that, compared to water, the sports drinks studied
      in this paper did not hydrate the body at a faster rate.

PMID- 17544329
TI  - Caffeine has a small effect on 5-km running performance of well-trained and
      recreational runners.
AB  - The purpose of this study was to investigate if caffeine ingestion improves 5-km
      time-trial performance in well-trained and recreational runners. Using a double
      blind placebo-controlled design, 15 well-trained and 15 recreational runners
      completed two randomized 5-km time-trials, after ingestion of either 5mgkg(-1) of
      caffeine or a placebo. Caffeine ingestion significantly improved 5-km running
      performance in both the well-trained and recreational runners. In comparison to
      the placebo trial, the caffeine trial resulted in 1.1% (90% CI 0.4-1.6) and 1.0%
      (0.2-2%) faster times for the well-trained and recreational runners. Reliability
      testing of the recreational runners indicated a test-retest error of measurement
      of 1.4%. We conclude that caffeine ingestion is likely to produce small but
      significant gains in 5-km running performance for both well-trained and
      recreational runners.

PMID- 17544330
TI  - Modern management of abnormal uterine bleeding: the levonorgestrel intra-uterine
      system.
AB  - Since its launch, more than 9 million women worldwide have used the
      levonorgestrel intra-uterine system (IUS) for contraception, as a treatment for
      heavy menstrual bleeding and as the progestogen component of hormone-replacement
      therapy. For women in their reproductive years, the IUS has become one of the
      most acceptable medical treatments for menorrhagia, reducing referrals to
      specialists and decreasing the need for operative gynaecological surgery. This
      article will outline the development of the IUS, highlighting the most important
      recent areas of research covering its use to control menstrual blood loss and
      pain.

PMID- 17544331
TI  - Suicidal ideation in epilepsy and levetiracetam therapy.
AB  - There is little literature on a possible link between the use of antiepileptic
      drugs (AEDs) and the occurrence of suicidal ideation. Nevertheless, its
      occurrence needs to be promptly recognized because it may trigger suicidal
      attempts. We retrospectively evaluated a case registry of 517 patients taking
      levetiracetam (LEV) for suicidal ideation, looking at possible clinical variables
      involved. Suicidal ideation was reported by four patients (0.7%). All cases
      occurred in the context of a mood disorder presenting early during LEV therapy.
      Psychopathological characteristics of suicidal ideation were consistent in all
      subjects and similar to some features that are described as typical of the so
      called interictal dysphoric disorder of epilepsy.

PMID- 17544332
TI  - Knowledge of and attitudes expressed toward epilepsy by carers of people with
      epilepsy: a UK perspective.
AB  - OBJECTIVE: The aim of this study was to investigate the knowledge and attitudes
      possessed by carers of people with epilepsy. METHODS: A postal survey of 2000
      carers recruited from the membership list of a UK epilepsy charity was conducted
      using a standard set of questions. The questions covered their knowledge of
      epilepsy (e.g., estimating prevalence and identifying causes of epilepsy) and
      their attitudes (e.g., about the characteristics of people with epilepsy).
      RESULTS: Overall, 651 carers responded. Only 29% of carers were male, with the
      majority between 40 and 60 years of age. The majority of respondents (76%)
      overestimated the prevalence of epilepsy. Twenty-five percent believed that
      epilepsy was caused by stress. The majority of respondents believed that people
      with epilepsy were treated differently by others. Only a small percentage
      believed that people with epilepsy should be barred from such professions as
      teaching and nursing. CONCLUSIONS: Carers of people with epilepsy generally
      possessed high levels of knowledge about most aspects of epilepsy, and their
      attitudes toward those with epilepsy were benign. There were, however, particular
      groups who were more likely to hold more positive attitudes, and these included
      younger and better-educated individuals. Limitations of this study include that
      the sample was self-selected and that only a third of the people to whom the
      questionnaire was mailed responded.

PMID- 17544333
TI  - WITHDRAWN: Lipid peroxidation and antioxidant defense systems in tissues of a
      lizard (Phrynocephalus przewalskii) during hibernation.
AB  - This article has been withdrawn consistent with Elsevier Policy on Article
      Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). The Publisher
      apologizes for any inconvenience this may cause.

PMID- 17544335
TI  - Prospective randomized trial of banded versus nonbanded gastric bypass for the
      super obese: early results.
AB  - BACKGROUND: Banded gastric bypass has been reported to result in superior weight
      loss compared with standard nonbanded gastric bypass. However, an adequate
      comparison of these procedures has not yet been reported. METHODS: A total of 90
      patients were enrolled in this prospective randomized double-blind trial
      comparing banded and nonbanded open gastric bypass for the treatment of super
      obesity. The banding technique involved placement of a 1.5 x 5.5-cm polypropylene
      band around the proximal gastric pouch of a standard gastric bypass procedure
      using the technique of Capella. Chi-square testing and analysis of variance were
      performed to find any differences in patient characteristics (gender, age, and
      initial body mass index), percentage of excess weight lost at 6, 12, 24, and 36
      months postoperatively, improvement or resolution of co-morbidities, and
      complications in the banded versus nonbanded gastric bypass groups. RESULTS: As
      expected, no differences were present in the patient characteristics or incidence
      of co-morbidities between the banded (n = 46) and nonbanded (n = 44) groups. The
      body mass index, percentage of women, and mean age was 59.5 and 56.5 kg/m2, 64%
      and 73.8% (P = .09), and 40.6 +/- 7.4 and 42.6 +/- 7.2 years for the banded and
      nonbanded groups, respectively; all differences were nonsignificant. No
      significant differences were found in the resolution of co-morbidities. No
      significant difference was present in the percentage of excess weight loss at 6,
      12, and 24 months (43.1% versus 24.7%, 64.0% versus 57.4%, and 64.2% versus
      57.2%, respectively) postoperatively; however, the banded patients had achieved a
      significantly greater percentage of excess weight loss at 36 months (73.4% versus
      57.7%; P <.05). The incidence of intolerance to meat and bread was greater in the
      banded patients. The overall number of complications was 12 (26%) in the banded
      and 13 (29.5%) in the nonbanded group, a nonsignficant difference. No band
      erosions had occurred at the last follow-up visit, and no patients in either
      group died. CONCLUSION: These results suggest that although the initial weight
      loss was not significantly different between the 2 groups, the banded patients
      continued to lose weight for < or = 3 years. The polypropylene band appeared to
      be well tolerated. We plan longer follow-up to confirm the possibility of
      additional weight loss and the prevention of weight regain in the banded group,
      as well as to document any long-term band complications.

PMID- 17544337
TI  - Optimal and minimax three-stage designs for phase II oncology clinical trials.
AB  - The common objective of oncology phase II trials is to evaluate the anti-tumor
      activity of a new agent and to determine whether the new drug warrants further
      investigation. For cancer drugs that significantly shrink tumors, response (CR
      and PR) rate is usually the primary endpoint in cancer phase II trials for
      testing H(0): P<or=P(0) vs H(1): P>or=P(1), where P(0) and P(1) are response
      rates which does not or does warrant further investigation given the rate of
      false positive (alpha) and false negative (beta). Multiple-stage designs
      including two-stage and three-stage have been developed by several authors. For
      example, Simon's optimal two-stage design [Simon R. Optimal two-stage designs for
      phase II clinical trials. Control Clin Trials 1989;10:1-10], Ensign et al.
      optimal three-stage design with restriction at the first stage [Ensign LG, Gehan
      EA, Kamen DS, Thall PF. An optimal three-stage design for phase II clinical
      trials. Stat Med 1994;13:1727-1736], Chen's optimal three-stage design without
      any restriction [Chen TT. Optimal three-stage designs for phase II clinical
      trials. Stat Med 1997;16:2701-2711], etc. However, all the above designs only
      early terminate a trial due to lack of activity of the study drug. Fleming's
      multiple-stage design [Fleming TR. One-sample multiple testing procedure for
      phase II clinical trials. Biometrics 1982;38:143-151] allows early stopping for
      either sufficient activity or lack of activity. But his design does not attempt
      to optimize its efficiency. We extend Chen's [Chen TT. Optimal three-stage
      designs for phase II clinical trials Stat Med 1997;16:2701-2711] design and
      propose an optimal and a minimax design for three-stage cancer phase II trials
      which allows early stopping under both hypotheses. The design is optimal in the
      sense that the average sample number (ASN) is minimized under P=P(0). The minimax
      design minimizes the maximal sample size (N) and then given this value of N
      minimizes the average sample number under P=P(0).

PMID- 17544338
TI  - Prevalence of abnormal liver-associated enzymes in cocaine experienced adults
      versus healthy volunteers during phase 1 clinical trials.
AB  - The frequency and nature of elevation of liver-associated enzymes (LAE) are
      important safety endpoints in Phase 1 clinical trials of new anti-cocaine agents,
      yet very little information is available on the prevalence of abnormal LAE in
      cocaine experienced adults. The aim of this retrospective study was to
      investigate the alterations of liver-associated enzymes (LAE) aspartate- (AST)
      and alanine transaminase (ALT), alkaline phosphatase (ALP), gamma glutamyl
      transferase (GGT), and bilirubin in healthy "normal" (HN) and cocaine experienced
      (actively using cocaine preadmission (CE)) adults participating in long term
      inpatient clinical trials. We examined LAE values collected from 3 inpatient
      Phase 1 trials of anti-cocaine agents. Analysis of variance (ANOVA) was applied
      to determine the significance of various factors on LAE alterations. Gender,
      baseline BMI, treatment did not demonstrate significant group differences in LAE
      levels. CE study volunteers were found to have significantly higher AST and ALT
      values than HN volunteers (P<0.05) during their respective inpatient stays. 94.1%
      of the 17 subjects with abnormal LAE were CE, and 37.5% of these CE received
      placebo. In conclusion, despite normal baseline values, most subjects
      demonstrated an increase in the ALT level even on placebo. For CE subjects,
      differences (Delta ALT and Delta AST) between baseline and the maximum observed
      values were significantly higher than that observed for HN subjects. The
      potential to obscure important signals for hepatotoxicity during Phase 1 research
      may be higher in the CE study population.

PMID- 17544339
TI  - Drug costs and out-of-pocket spending in cancer clinical trials.
AB  - OBJECTIVE: To estimate the effect of clinical trial participation on drug
      utilization, drug costs, and out-of-pocket expenditures for cancer patients.
      METHODS: The study used a national probability sample of patients participating
      in cancer clinical trials and a matched cohort of patients not enrolled in trials
      but receiving treatment for the same cancers from the same providers. Subjects
      were interviewed about prescription drug utilization and out-of-pocket drug
      expenditures. We estimated treatment costs based on a large pharmacy transaction
      database. Multivariate regression was used to estimate the effects of trial
      participation on drug costs and out-of-pocket expenditures. RESULTS: Participants
      in clinical trials incurred higher prescription drug costs than non-participants:
      an average of $131 over a six-month period. However, there was no significant
      difference in out-of-pocket expenditures for the two groups. CONCLUSIONS:
      Participation in clinical trials was associated with a modest increase in
      prescription drug utilization and costs, but these costs did not necessarily
      impose an economic burden on cancer trial participants.

PMID- 17544340
TI  - Use of deception to achieve double-blinding in a clinical trial of Melaleuca
      alternifolia (tea tree) oil for the treatment of recurrent herpes labialis.
AB  - Double-blinding is an important and widely implemented feature of clinical trials
      although its success is rarely assessed. In a randomized, placebo-controlled
      trial of tea tree oil, an aromatic essential oil, for the treatment of recurrent
      herpes labialis (RHL), or cold sores, deception was used to prevent volunteers
      from identifying their treatment allocation. Volunteers received placebo (n=102)
      or tea tree oil (n=112) ointment in preparation for their next episode of RHL and
      were told, falsely, that the aroma of the ointments had been changed to prevent
      identification of the treatment group. At the trial's end, of the volunteers who
      had used their ointment and presented for treatment assessment (n=100),
      approximately 50% correctly guessed their treatment allocation (P=0.774). Amongst
      volunteers that had not presented for treatment assessment (n=114), 12 volunteers
      did not provide blinding data and 46 did not open their tube. For the 56
      volunteers who opened their tube, less than half of those receiving tea tree oil
      (44.4%) and only a small proportion of those on placebo (17.2%) were able to
      correctly identify their treatment allocation. Among the volunteers that were not
      treated, the P-value was 0.083. This study showed that the ethical use of
      deception may provide effective blinding in challenging circumstances.

PMID- 17544341
TI  - Expression patterns of chick Musashi-1 in the developing nervous system.
AB  - Vertebrate homologues of musashi have recently been referred to as neural stem
      cell markers because of their expression patterns and RNA-binding interactions.
      In the context of the notch signaling pathway, Musashi-1 (Msi-1) is a regulator
      of neural cell generation, cooperating with notch to maintain mitosis. In an
      effort to identify definitive stem cell markers of the neural retina, a portion
      of the Msi-1 cDNA was cloned, and the expression of Msi-1 in the chick eye was
      analyzed. Using an Msi-1-specific antibody and RNA probe, we show that expression
      of Msi-1 in the early neural tube is consistent with neural stem identity. In the
      neural retina, expression starts shortly before embryonic day 3 (E3) and
      continues up to and including E18. A BrdU incorporation assay shows Msi-1 to be
      found in both proliferating and differentiating cells of E5 neural retina. At E8
      (when proliferation is complete in the fundus of the retina) and E18 (mature
      retina) Msi-1 expression was found in the ciliary marginal zone (CMZ) as well as
      in a subpopulation of differentiated cells, including photoreceptors and ganglion
      cells.

PMID- 17544342
TI  - Electrical signaling in Aloe vera induced by localized thermal stress.
AB  - Action potentials in higher plants are theorized as the information carriers in
      intercellular and intracellular communication in the presence of environmental
      stressors. Among the most common stressors is heat shock. Under stressful
      conditions, the response reactions of plant tissues and organs can be local or
      transmitted over long distances. In this article, the speeds of propagation of
      thermally induced action potentials in green plants are discussed, and their
      speeds were found to be comparable to those occurring in various mammalian
      species. These rapid action potentials in green plants were recorded in real time
      using modern data acquisition techniques. According to our measurements, a single
      application of localized heat stress induces fast action potentials in Aloe vera
      (67 m/s). Electrical signals propagated along all leaves of the A. vera plants
      were studied. Possible pathways for electrical signal propagation in vascular
      plants are also discussed.

PMID- 17544343
TI  - Liquid chromatography-tandem mass spectrometric assays for salinomycin in mouse
      plasma, liver, brain and small intestinal contents and in OptiMEM cell culture
      medium.
AB  - Fast and sensitive liquid chromatography-tandem mass spectrometric assays for the
      determination of salinomycin in mouse plasma, liver, brain and small intestinal
      contents and in OptiMEM cell culture medium, were developed and validated using
      simple sample pre-treatment procedures. Tissue samples were homogenized with
      phosphate buffered saline or, for high levels in liver, with human plasma. After
      addition of monensin as the internal standard to plasma, homogenate or culture
      medium and acetonitrile extraction for tissue and plasma, the diluted medium or
      the supernatant was directly injected into the isocratic chromatographic system
      using a polar embedded reversed-phase column and formic acid in water
      acetonitrile as the eluent. The eluate was completely led into an electrospray
      interface with positive ionization and the analytes were quantified using triple
      quadrupole mass spectrometry. The assays were successfully validated in the
      ranges 10-2000 ng/ml for OptiMEM cell culture medium, 1-2000 ng/ml for plasma and
      3-2000 ng/g in liver brain and small intestinal contents. At the lowest levels,
      the intra-day precisions were < or =9%, inter-day precisions were < or =14% and
      accuracies were between 91 and 112%. The analytes were chemically stable under
      all relevant conditions and the assays were applied in different in vitro
      transport studies and in pharmacokinetic and tissue distribution studies with
      salinomycin in mice.

PMID- 17544344
TI  - Improved and simplified liquid chromatography/electrospray ionization mass
      spectrometry method for the analysis of underivatized glucosamine in human
      plasma.
AB  - Glucosamine is an amino monosaccharide reagent. It is difficult to assay using
      typical reversed-phase column due to the early elution, by optimizing the
      chromatographic conditions, especially the analytical column and the mobile phase
      composition, an improved analytical method was developed and validated, which
      offers rapid, sensitive and specific determination of glucosamine in human
      plasma. Following protein precipitation, the analyte and internal standard
      (valibose) were separated using an isocratic mobile phase on an Inertsil CN-3
      column and detected by mass spectrometry in the multiple reaction monitoring mode
      using the respective precursor to product ion combinations of m/z 180/72 for
      glucosamine and m/z 252/198 for valibose. The chromatographic time was just 4.2
      min for each sample, which made it possible to analyze more than 120 human plasma
      samples per day. The method exhibited a linear dynamic range of 4.00-4000 ng/mL
      for glucosamine in human plasma. The lower limit of quantification (LLOQ) was
      4.00 ng/mL with a relative standard deviation of less than 10.9%. Acceptable
      precision and accuracy were obtained for the plasma concentrations over the
      standard curve range. By monitoring the two different MRM transitions, it was
      proved that no endogenous glucosamine was found in human plasma. The validated
      method has been successfully used to analyze human plasma samples for application
      in a bioequivalence study.

PMID- 17544345
TI  - Purification and partial characterization of N-hydroxy-l-phenylalanine
      decarboxylase/oxidase from Bacillus sp. strain OxB-1, an enzyme involved in
      aldoxime biosynthesis in the "aldoxime-nitrile pathway".
AB  - An enzyme that catalyzes the conversion of N-hydroxy-l-phenylalanine to
      phenylacetaldoxime was shown to be present in the Z-phenylacetaldoxime-degrading
      bacterium, Bacillus sp. strain OxB-1. The aldoxime-forming enzyme, which is
      induced by L-phenylalanine, was purified 8,050-fold to apparent homogeneity with
      a yield of 15.2%. The enzyme has a subunit M(r) of about 86,000. The enzyme
      converts N-hydroxy-L-phenylalanine (K(m) 0.99 mM) to only one geometrical isomer,
      namely Z-phenylacetaldoxime. Relatively large amounts of pyridoxal 5'-phosphate
      (PLP) are required to be present in the reaction mixture because PLP reacts non
      enzymatically with the N-hydroxy amino acid substrate to form a nitrone. Several
      characteristics of the enzyme were compared with those of other PLP-dependent
      aromatic amino acid-converting enzymes described in the literature. The enzyme is
      tentatively named "N-hydroxy-L-phenylalanine decarboxylase/oxidase". Finally, the
      possible biosynthesis and metabolism of phenylacetaldoxime in Bacillus sp. strain
      OxB-1 is discussed.

PMID- 17544346
TI  - Reconstitution of apoglucose oxidase with FAD conjugates for biosensoring of
      progesterone.
AB  - The reconstitution of Aspergillus niger apoglucose oxidase (apoGOx) with FAD
      conjugates for biosensoring of progesterone was investigated. ApoGOx prepared by
      partial unfolding of the protein under acidic conditions consisted of
      reconstitutable monomers (50+/-10%), reconstitutable dimers (20+/-10%) and
      irreversibly aggregated oligomers (30+/-20%). Incubation of monomeric apoGOx with
      FAD or N(6)-(6-aminohexyl)-FAD (ahFAD) restored glucose oxidase (GOx) activity
      and induced dimerization with stoichiometric incorporation of FAD. N(6)-(6
      aminohexyl)-FAD progesterone conjugates also induced dimerization. However,
      holoenzyme reconstitution required relatively high concentrations of apoprotein
      and was dependent on the type of conjugate. Restoration to 25-50% of the original
      enzyme activity was obtained. Binding of the FAD-progesterone conjugates might
      hinder the closure of a protein lid needed for dimer formation. Our results
      illustrate the prospects of FAD conjugates in sensitive detection of progesterone
      in biological matrices in a biosensor based on the recombination of apoGOx with
      progesterone-conjugated FAD.

PMID- 17544347
TI  - The inhibition kinetics and thermodynamic changes of tyrosinase via the zinc ion.
AB  - We found that Zn(2+) conspicuously inactivated tyrosinase in a mixed-type
      inhibition manner: the final level of residual activity was abolished at the
      equilibrium state with concentration of 0.25 mM Zn(2+). Changes of both K(m) and
      V(max) by various concentrations of Zn(2+) in Lineweaver-Burk plot were observed.
      To see whether Zn(2+) also induced conformational change of tyrosinase and how
      thermodynamical changes by ligand binding were occurred, the intrinsic
      fluorescence studies as well as calorimetric measurements were conducted. The
      results showed that the Zn(2+) binding to tyrosinase directly induced
      conformational change of tyrosinase, and the changes of thermodynamic parameters
      such as enthalpy (DeltaH), Gibbs free-energy (DeltaG), and entropy (DeltaS) were
      obtained as 60+/-7.0 kJ/mol, -14.54 kJ/mol and 248.53 J/(K mol), respectively.
      The inactivating effect of Zn(2+) on tyrosinase was completely prevented by
      incubation with bovine serum albumin, which has a Zn(2+) binding motif in its
      structure. We suggested that Zn(2+) ligand-binding affected the substrate's
      accessibility due to the conformational changes and thus, the complex type of
      inhibition has occurred with the calorimetric changes.

PMID- 17544349
TI  - Absorbable mesh and topical negative pressure therapy for closure of abdominal
      dehiscence with exposed bowel.
AB  - Permacol mesh is a porcine dermis-derived biomaterial used for the repair of
      abdominal incisional and inguinal hernia. It has been found to be a safe and
      effective alternative to non-absorbable mesh for application over exposed bowel.
      This mesh has also been successfully applied over contaminated abdominal wound
      beds and around stomas. Topical negative pressure therapy has been used for the
      management of wound complications after surgical implantation of Permacol mesh.
      We describe our experience with the combined use of Permacol mesh and
      simultaneous application of topical negative pressure therapy to aid wound
      contraction and granulation in a patient with abdominal dehiscence and exposed
      bowel.

PMID- 17544350
TI  - A retrospective audit of Novagold 'hydrogel' breast implants.
AB  - Novagold breast implants were withdrawn from use in the UK in December 2000 due
      to concerns about the metabolic fate of the implant filler material, the
      hydrogels polyvinylpyrrolidine (PVP) and guar gum. A total of 250 women in the UK
      had these implants, 66 of which were performed in our unit. A total of 44% of
      cases needed further surgery for complications. Capsular contracture requiring
      surgical intervention occurred in 32%. Symptomatic ruptures occurred in 10.5%.
      Infection was recorded in 1.5%. From comparison with published data, the
      incidence of capsular contracture is comparable, but the occurrence of rupture is
      almost twice that of saline-filled implants. It is hypothesised that an osmotic
      gradient occurs due to the hydrogel filler causing the implants to swell and
      weaken the elastomer shell. When the PVP/guar gum filler is released into the
      subcutis, a vigorous tissue reaction occurs causing pain and swelling. These
      results show that this composition of implant poses potential risks, which should
      be considered by manufacturers in the future. We advise removal of symptomatic
      implants, as rupture is likely to have occurred.

PMID- 17544351
TI  - Clinical audit of the impact of information leaflets on outcomes in patients with
      mallet finger injuries.

PMID- 17544352
TI  - Individual and combined effects of exercise and alendronate on bone mass and
      strength in ovariectomized rats.
AB  - Exercise and bisphosphonate therapies increase bone strength by primarily
      increasing bone formation and reducing resorption, respectively. Based on these
      different mechanisms of action, it is possible that combined introduction of
      exercise and bisphosphonate therapies generates greater improvements in bone mass
      and strength than either intervention alone. The aim of this study was to examine
      the individual and combined effects of exercise (treadmill running) and
      bisphosphonate therapy (alendronate [ALN]) on bone mass and strength in
      ovariectomized (OVX) rats. Seven-month-old virgin female rats were randomly
      assigned to either a sham-OVX group (n=13) or one of four OVX groups: vehicle
      treated cage-control (VEH-CON, n=10); ALN-treated cage-control (ALN-CON, n=13);
      vehicle-treated plus treadmill running (VEH-RUN, n=13); and ALN-treated plus
      treadmill running (ALN-RUN, n=13). ALN-treated groups received twice-weekly ALN
      (0.015 mg/kg), and exercise groups ran on a motorized treadmill at a 5% incline
      for 60 min/day, 22-24 m/min, 5 days/week. In vivo measurements included dual
      energy X-ray absorptiometry (DXA) of whole-body bone mineral content (BMC), and
      ex vivo measurements included DXA, micro-computed tomography (muCT), and
      mechanical testing of the femur and L4 vertebrae. After 14 weeks of intervention,
      exercise and ALN had additive benefits on whole body and proximal femur BMC,
      cross-sectional area of the L4 vertebrae, and mechanical properties of the mid
      shaft femur. In comparison, for total and mid-shaft femur BMC, L4 vertebrae BMC,
      and mid-shaft femur cortical thickness and area, there were significant exercise
      and ALN interactions indicating that the two interventions worked in synergy to
      enhance bone properties. Supporting the contention that ALN and exercise function
      via distinct mechanisms of action, ALN successfully reduced medullary canal area
      suggesting it reduced endocortical bone resorption, whereas exercise augmented
      periosteal perimeter suggesting it stimulated periosteal bone formation. In
      summary, we found combined treadmill running and ALN to be more beneficial in
      preventing declines in bone mass and strength following OVX than the introduction
      of either intervention alone. These data suggest that a comprehensive program of
      bisphosphonate therapy and weight-bearing exercise may be an effective method for
      preventing and treating osteoporosis in post-menopausal women.

PMID- 17544353
TI  - A microculture technique for isolating live Leishmania parasites from peripheral
      blood of visceral leishmaniasis patients.
AB  - Current procedures for diagnosing Leishmania parasites from patients involve
      invasive and dangerous tissue aspiration. We have developed a non-invasive and
      highly sensitive microculture method that can isolate parasites from the buffy
      coat of the patient's peripheral blood. The parasites were cultured in 96-well
      culture plates. Nineteen parasitologically proven visceral leishmaniasis (VL)
      patients were included in the study. Using this technique, we were able to
      isolate parasites from 16 (84%) samples. However, all 19 (100%) samples were
      positive on culture of splenic aspirates. We conclude that this technique is
      useful for the isolation and cryoconservation of parasites from patients' blood.
      This simple method could be tried as a first-instance alternative before other
      more sensitive procedures such as splenic aspirate; however, negative results
      should be confirmed by tests with higher sensitivity.

PMID- 17544354
TI  - Infection of adult Aedes aegypti and Ae. albopictus mosquitoes with the
      entomopathogenic fungus Metarhizium anisopliae.
AB  - This study describes a laboratory investigation on the use of the insect
      pathogenic fungus Metarhizium anisopliae against adult Aedes aegypti and Ae.
      albopictus mosquitoes. At a dosage of 1.6 x 10(10)conidia/m(2), applied on
      material that served as a mosquito resting site, an average of 87.1+/-2.65% of
      Ae. aegypti and 89.3+/-2.2% of Ae. albopictus became infected with the fungus.
      The life span of fungus-contaminated mosquitoes of both species was significantly
      reduced compared to uninfected mosquitoes. LT(50)-values of fungus-contaminated
      mosquitoes ranged between 3.1+/-0.2 days (male Ae. aegypti) and 4.1+/-0.3 days
      (female Ae. aegypti). LT(50)-values of uncontaminated mosquitoes ranged from
      17.7+/-0.4 days (female Ae. albopictus) to 19.7+/-0.6 days (male Ae. albopictus).
      These results indicate that both mosquito species are highly susceptible to
      infection with this entomopathogen. Requirements for developing and incorporating
      this biological control method into current strategies to control major diseases
      vectored by these species, such as dengue fever, are discussed.

PMID- 17544355
TI  - Molecular surveillance for drug-resistant Plasmodiumfalciparum malaria in Malawi.
AB  - We assessed the presence of point mutations associated with resistance to
      chloroquine (CQ) and sulphadoxine-pyrimethamine (SP) in 178 Plasmodiumfalciparum
      infections from three geographically distinct sites in Malawi. We confirm that CQ
      resistance mutations are now rare in Malawi, being detectable at very low
      frequencies (2-4%) in infections from two of the three study sites. We also show
      that over 90% of infections from each of the three study sites carry a set of
      three dihydrofolate reductase (dhfr) and two dihydropteroate synthase (dhps)
      mutations strongly associated with SP treatment failure. In this short
      communication, we present these molecular data and discuss their implications for
      Malawi's first-line antimalarial treatment policy.

PMID- 17544356
TI  - Gravity as a factor of aggregative stability and coagulation.
AB  - Gravity is a potential factor of aggregative stability and/or coagulation for any
      heterogeneous system having a density contrast between the dispersed phase and
      its dispersion medium. However, gravity becomes comparable to other stability
      factors only when the particle size becomes large enough. Since the particle size
      may grow in time due to various other instabilities, even nano-systems may
      eventually become susceptible to gravity. There have been many attempts in the
      last century to incorporate gravity in the overall theory of aggregative
      stability, but the relevant papers are scattered over a wide variety of journals,
      some of which are very obscure. Reviews on this subject in modern handbooks are
      scarce and inadequate. No review describes the role of gravity at all three
      levels introduced by DLVO theory for characterizing aggregative stability,
      namely: particle pair interaction, collision frequency and population balance
      equation. Furthermore, the modern tendency towards numerical solutions
      overshadows existing analytical solutions. We present a consistent review at each
      DLVO level. First we describe the role of gravity in particle pair interactions,
      including both available analytical solutions as well as numerical stability
      diagrams. Next we discuss a number of works on collision frequency, including
      works for both charged and non-charged particles. Finally, we present analytical
      solutions of the population balance equation that takes gravity into account and
      then compare these analytical solutions with numerical solutions. In addition to
      the traditional aggregate model we also discuss work on a fractal model and its
      relevance to gravity controlled stability. Finally, we discuss many experimental
      works and their relationship to particular theoretical predictions.

PMID- 17544357
TI  - Comparison of surface and hydrogel-based protein microchips.
AB  - Protein microchips are designed for high-throughput evaluation of the
      concentrations and activities of various proteins. The rapid advance in microchip
      technology and a wide variety of existing techniques pose the problem of unified
      approach to the assessment and comparison of different platforms. Here we compare
      the characteristics of protein microchips developed for quantitative immunoassay
      with those of antibodies immobilized on glass surfaces and in hemispherical gel
      pads. Spotting concentrations of antibodies used for manufacturing of microchips
      of both types and concentrations of antigen in analyte solution were identical.
      We compared the efficiency of antibody immobilization, the intensity of
      fluorescence signals for both direct and sandwich-type immunoassays, and the
      reaction-diffusion kinetics of the formation of antibody-antigen complexes for
      surface and gel-based microchips. Our results demonstrate higher capacity and
      sensitivity for the hydrogel-based protein microchips, while fluorescence
      saturation kinetics for the two types of microarrays was comparable.

PMID- 17544358
TI  - Polymorphism of the FSH receptor and ovarian response to FSH.
AB  - Follicle-stimulating hormone (FSH) is a key factor in human reproduction. FSH
      activates its receptor (FSHR) located exclusively on Sertoli cells in the testis
      and granulosa cells in the ovary. Two common single nucleotide polymorphisms
      (SNP) within exon 10 of the human FSHR gene result in two almost equally common
      allelic variants exhibiting threonine (Thr) or alanine (Ala) at position 307 in
      the hinge region, respectively, asparagine (Asn) or serine (Ser) at codon 680 of
      the intracellular domain. Clinical studies have demonstrated that p.N680S
      polymorphism determines the ovarian response to FSH stimulation in patients
      undergoing IVF-treatment. Patients with the Ser(680) allele need more FSH during
      the stimulation phase to reach the serum estradiol levels of Asn(680) patients. A
      study investigating women with normal, mono-ovulatory menstrual cycles revealed
      that the Ser(680)/Ser(680) genotype leads to higher FSH serum levels and a
      prolonged cycle. To date, the molecular mechanism underlying the partial
      "resistance" of the Ser(680)-FSHR to FSH remains unclear. Future experiments
      should extend our current understanding of FSH action on follicular selection and
      dominance, thereby permitting novel, patient-tailored therapies for infertility
      and fertility preservation.

PMID- 17544359
TI  - [Steroid responsive encephalopathy associated with auto-immune thyroiditis: a
      revisited entity].

PMID- 17544360
TI  - The conformational and property space of acetylcholine bound to muscarinic
      receptors: an entropy component accounts for the subtype selectivity of
      acetylcholine.
AB  - The conformational behavior of receptor-bound acetylcholine (ACh) was
      investigated by molecular dynamics simulations. Based on the great similarity
      among muscarinic receptors, the study was focused on the human M(1), M(2), and
      M(5) receptors as previously modeled by us. The results showed that receptor
      bound ACh was not frozen in a single preferred conformation but preserved an
      unexpected fraction of its conformational space. However, there were marked
      differences between the three receptors since the ligand was mostly trans in the
      M(1) receptor, equally distributed among trans and gauche conformers in M(2), and
      exclusively gauche in the M(5); the greater flexibility of M(2)-bound ACh was
      paralleled by the greater flexibility of the occupied M(2) binding site. By
      contrast, the property space of receptor-bound ACh, and particularly its virtual
      (computed, conformation-dependent) lipophilicity, was restricted to relatively
      narrow ranges optimal for successful interaction. Experimental binding
      investigations to the individual human M(1), M(2), and M(5) muscarinic receptors
      showed ACh to have a 10-fold higher affinity for the M(2) compared to the M(1)
      and M(5) receptors. This selectivity was not confirmed by the calculated binding
      scores, a fact postulated to be caused by the absence of an entropy component in
      such binding scores. Indeed, the Shannon entropy of all geometric and
      physicochemical properties monitored were markedly higher in M(2)-bound ACh
      compared to M(1)-bound and M(5)-bound ACh. This finding suggests that the
      selectivity profile of acetylcholine for the M(2) receptor is largely entropy
      driven, a fact that might explain the intrinsic difficulty to design subtype
      selective muscarinic agonists.

PMID- 17544361
TI  - A comparison of acceptance- and control-based strategies for coping with food
      cravings: an analog study.
AB  - The present study utilized an analog paradigm to investigate the effectiveness of
      two strategies for coping with food cravings, which was theorized to be critical
      to the maintenance of weight loss. Ninety-eight undergraduate students were given
      transparent boxes of chocolate Hershey's Kisses and instructed to keep the
      chocolates with them, but not to eat them, for 48 h. Before receiving the Kisses,
      participants were randomized to receive either (a) no intervention, (b)
      instruction in control-based coping strategies such as distraction and cognitive
      restructuring, or (c) instruction in acceptance-based strategies such as
      experiential acceptance and defusion techniques. Measures included the Power of
      Food Scale (PFS; a measure of psychological sensitivity to the food environment),
      self-report ratings of chocolate cravings and surreptitiously recorded chocolate
      consumption. Results suggested that the effect of the intervention depended on
      baseline PFS levels, such that acceptance-based strategies were associated with
      better outcomes (cravings, consumption) among those reporting the highest
      susceptibility to the presence of food, but greater cravings among those who
      scored lowest on the PFS. It was observed that craving self-report measures
      predicted chocolate consumption, and baseline PFS levels predicted both cravings
      and consumption. Results are discussed in terms of the implications for weight
      loss maintenance strategies.

PMID- 17544362
TI  - GRK2 interacts with and phosphorylates Nedd4 and Nedd4-2.
AB  - Epithelial Na(+) channels (ENaC) mediate the transport of sodium (Na) across
      epithelia in the kidney, gut, and lungs and are required for blood pressure
      regulation. They are inhibited by ubiquitin protein ligases, such as Nedd4 and
      Nedd4-2, which bind to proline-rich motifs (PY motifs) present in the C-termini
      of ENaC subunits. Loss of inhibition leads to hypertension. ENaC channels are
      maintained in the active state by G-protein-coupled receptor kinase 2 (GRK2), an
      enzyme implicated in the development of essential hypertension. Here, we report
      that GRK2 interacts not only with ENaC, but also with both Nedd4 and Nedd4-2.
      Additionally, GRK2 is capable of phosphorylating both Nedd4 and Nedd4-2 at
      multiple sites. Of possible significance is the phosphorylation of the threonine
      at position 466 in Nedd4, which is located in the area of the ww3 domain that
      binds ENaC. These results support and extend the role of GRK2 in sodium transport
      regulation.

PMID- 17544363
TI  - Homocysteine induces cell death in H9C2 cardiomyocytes through the generation of
      peroxynitrite.
AB  - Homocysteine (HCY) is toxic on blood vessels, but a potential direct toxicity of
      HCY on the heart is unknown. We addressed this issue by exposing H9C2
      cardiomyocytes to HCY (0.1-5 mM) for up to 6h. At these concentrations, HCY
      reduced cell viability, induced necrosis and apoptosis and triggered the cleavage
      of caspase-3 and poly(ADP-ribose) polymerase (PARP). This was associated with the
      intracellular generation of the potent oxidant peroxynitrite. Removing
      peroxynitrite by the decomposition catalyst FeTPPS considerably reduced LDH
      release, DNA fragmentation, cleavage of caspase-3 and PARP, and restored normal
      cell morphology. In additional experiments performed in primary rat ventricular
      cardiomyocytes, HCY (1 mM, 6h) activated the phosphorylation of the MAP kinases
      ERK and JNK, two essential stress signaling kinases regulating myocardial
      apoptosis, hypertrophy and remodeling. These results provide the first
      demonstration that HCY kills cardiomyocytes through the generation of
      peroxynitrite and can activate key signaling cascades in the myocardium.

PMID- 17544364
TI  - Specific expression of GFPuv-beta1,3-N-acetylglucosaminyltransferase 2 fusion
      protein in fat body of Bombyx mori silkworm larvae using signal peptide.
AB  - Bombyxin (bx) and prophenoloxidase-activating enzyme (ppae) signal peptides from
      Bombyx mori, their modified signal peptides, and synthetic signal peptides were
      investigated for the secretion of GFP(uv)-beta1,3-N-acetylglucosaminyltransferase
      2 (GGT2) fusion protein in B. mori Bm5 cells and silkworm larvae using cysteine
      protease deficient B. mori multiple nucleopolyhedrovirus (BmMNPV-CP(-)) and its
      bacmid. The secretion efficiencies of all signal peptides were 15-30% in Bm5
      cells and 24-30% in silkworm larvae, while that of the +16 signal peptide was 0%
      in Bm5 cells and 1% in silkworm larvae. The fusion protein that contained the +16
      signal peptide was expressed specifically in the endoplasmic reticulum (ER) and
      in the fractions of cell precipitations. Ninety-four percent of total
      intracellular beta1,3-N-acetylglucosaminyltransferase (beta3GnT) activity was
      detected in cell precipitations following the 600, 8000, and 114,000g
      centrifugations. In the case of the +38 signal peptide, 60% of total
      intracellular activity was detected in the supernatant from the 114,000g spin,
      and only 1% was found in the precipitate. Our results suggest that the +16 signal
      peptide might be situated in the transmembrane region and not cleaved by signal
      peptidase in silkworm or B. mori cells. Therefore, the fusion protein connected
      to the +16 signal peptide stayed in the fat body of silkworm larvae with
      biological function, and was not secreted extracellularly.

PMID- 17544365
TI  - HDL-like lipoproteins in cerebrospinal fluid affect neural cell activity through
      lipoprotein-associated sphingosine 1-phosphate.
AB  - High-density lipoprotein (HDL)-associated sphingosine 1-phosphate mediates a
      variety of lipoprotein-induced actions in vascular cell systems. However, it
      remains unknown whether extracellular S1P is associated with lipoproteins to
      exert biological actions in central nervous system. Human cerebrospinal fluid
      (CSF) induced rat astrocyte migration in a manner sensitive to S1P receptor
      antagonist VPC23019 and the migration activity was recovered in S1P fraction by
      thin-layer chromatography. Density-gradient separation of CSF revealed that the
      major S1P activity was detected in the HDL fraction. In conditioned medium of rat
      astrocytes cultured with sphingosine, the S1P activity was recovered again in the
      HDL fraction. The HDL fraction also induced migration of astrocytes and process
      retraction of oligodendrocytes in a manner similar to S1P. We concluded that S1P
      is accumulated in HDL-like lipoproteins in CSF and mediates some of lipoprotein
      induced neural cell functions in central nervous system.

PMID- 17544366
TI  - Effects of genetic polymorphisms of UCP2 and UCP3 on very low calorie diet
      induced body fat reduction in Korean female subjects.
AB  - The uncoupling protein (UCP) family has been suggested as a possible determinant
      affecting obesity risk given their function in the regulation of energy
      metabolism. In an effort to elucidate the effects of UCP family polymorphisms on
      obesity phenotypes, we genotyped 10 polymorphisms in UCP2 and UCP3 among
      overweight female subjects (n=458), and genetic effects on BMI and changes after
      a very low calorie diet (VLCD) were examined. Analyses of VLCD-induced changes
      among the subjects who had finished one month-weight control program (n=301)
      revealed that several polymorphisms in UCP2-3 gene cluster showed associations
      with changes of BMI and fat mass, however not of protein mass. One of the major
      haplotypes of UCP2-3 gene cluster, ht1 (GGCdelCGTACC), and UCP2-866G>A showed
      significant associations with VLCD-induced fat reduction (P=0.002 and 0.004;
      P(corr)=0.03 and 0.01, respectively), and these results suggested that UCP2-3
      polymorphisms were important genetic factor for the VLCD-induced reduction of
      body fat mass.

PMID- 17544367
TI  - Nitric oxide modulation of voltage-gated calcium current by S-nitrosylation and
      cGMP pathway in cultured rat hippocampal neurons.
AB  - Nitric oxide (NO) plays an important role in many physiological and
      pathophysiological processes in the brain. In this study, we examined the
      mechanistic effects of an NO donor, diethylenetriamine/nitric oxide adduct
      (DETA/NO) on the voltage-gated calcium currents in cultured rat hippocampal
      neurons. DETA/NO stimulated the calcium currents and slightly increased the
      channel sensitivity to depolarizing voltages. The effect of DETA/NO on the
      calcium current was blocked by either depleting the NO in DETA/NO or by
      pretreating the neurons with NEM, a thiol-specific alkylating agent, suggesting
      an involvement of S-nitrosylation in the current response to NO. In addition,
      activation of the cGMP pathway by 8-Br-cGMP inhibited the calcium current in the
      neurons. Also, inhibition of guanylyl cyclase by 1H-[1,2,4] oxadiazolo [4,3-a]
      quinoxalin-1-one (ODQ) increased the current response to DETA/NO. Taken together,
      our results demonstrate that both S-nitrosylation and cGMP pathway are involved
      in the NO modulation of the hippocampal calcium current.

PMID- 17544368
TI  - Discovery of gliotoxin as a new small molecule targeting thioredoxin redox
      system.
AB  - Thioredoxin redox system has been implicated as an intracellular anti-oxidant
      defense system leading to reduction of cellular oxidative stresses utilizing
      electrons from NADPH. From high content screening of small molecules targeting
      the system, gliotoxin, a fungal metabolite, was identified as an active compound.
      Gliotoxin potently accelerates NADPH oxidation and reduces H(2)O(2). The compound
      reduces H(2)O(2) to H(2)O by replacing the function of peroxiredoxin in vitro and
      decreases intracellular level of H(2)O(2) in HeLa cells. The anti-oxidant
      activity of gliotoxin was further validated H(2)O(2)-mediated cellular phenotype
      of angiogenesis. The proliferation of endothelial cells was inhibited by the
      compound at nanomolar range. In addition, H(2)O(2)-induced tube formation and
      invasion of the cells were blocked by gliotoxin. Together, these results
      demonstrate that gliotoxin is a new small molecule targeting thioredoxin redox
      system.

PMID- 17544369
TI  - Inhibition of RANKL-mediated osteoclast differentiation by selective TRAF6 decoy
      peptides.
AB  - RANK and RANKL are essential mediators of osteoclastogenesis. RANK interacts with
      members of the tumor necrosis factor receptor-associated factor (TRAF) family, of
      which TRAF6 is the critical signaling molecule. We identified a unique TRAF6
      binding motif in RANK, which was subsequently co-crystallized with TRAF6
      revealing distinct molecular interactions. A cell-permeable TRAF6 decoy peptide
      (T6DP) was shown to specifically target TRAF6 and inhibit RANKL-mediated
      signaling. In this study, we identified a core motif for binding to TRAF6 by
      generating a series of deletion mutants linked via palmitate as a means to
      internalize the peptide, thus making a smaller scaffold for intracellular
      delivery. The core motif of RKIPTEDEY inhibited RANKL-mediated osteoclastogenesis
      and bone resorption. In contrast, TRAF2/5 decoy peptides appeared to have no
      affect. Thus, disruption of the RANK-TRAF6 interaction may prove useful as a
      novel target for the development of a small molecule therapeutic agent for the
      treatment of bone-related diseases.

PMID- 17544370
TI  - Constitutive over-expression of VEGF results in reduced expression of Hand-1
      during cardiac development in Xenopus.
AB  - During heart development, various signaling cascades are tightly regulated in a
      stage- and region-dependent manner. Vascular endothelial growth factor (VEGF) is
      one of the important molecules required for both vascular development and cardiac
      morphogenesis. VEGF receptors are present in the embryonic heart, so we focused
      on heart formation in VEGF-over-expressing Xenopus embryos. Over-expression of
      VEGF(170) caused disorganized vessels, while the expression of an endothelial
      marker, Tie-2, was increased. The embryo's heart was distinctly larger than that
      of control, and showed abnormal morphology. Histological analysis of these
      embryos showed failure of heart looping. In situ hybridization with Hand-1, which
      controls intrinsic morphogenetic pathways, revealed that the expression level of
      Hand-1 was decreased in the heart region. These results suggest that increased
      VEGF(170) levels disturb Hand-1 expression in the region required for normal
      heart morphogenesis. VEGF expression level may be important in heart morphology
      during embryonic development.

PMID- 17544371
TI  - TRAF-interacting protein (TRIP) is a RING-dependent ubiquitin ligase.
AB  - TRAF-interacting protein (TRIP) was initially identified as a TRAF1- and TRAF2
      binding partner that inhibited NF-kappaB activation without a known mechanism.
      Inspection of the TRIP sequence revealed an N-terminal RING domain, which is
      found in many E3 ubiquitin (Ub) ligases. We show that TRIP is a RING-dependent Ub
      ligase that undergoes auto-ubiquitination and requires an intact RING domain.
      Both TRIP and its RING mutant interact with TRAF1, 2, 3, 5, and 6, but failed to
      interact with CYLD and NIK. Stable expression of TRIP or a RING mutant did not
      affect IKK activation induced by TNF or IL-1 and had no affect on TNF-induced
      apoptosis. Similarly, RANKL-induced signaling and osteoclastogenesis were not
      affected by TRIP or its RING mutant. Interestingly, TRIP expression was down
      regulated during the late stages of osteoclastogenesis. Taken together, our
      results demonstrate that TRIP is a novel RING-dependent Ub ligase and a binding
      partner for TRAFs.

PMID- 17544372
TI  - Identification of SNAREs that mediate zymogen granule exocytosis.
AB  - A secretagogue-stimulated pancreatic acinar cell releases digestive enzymes from
      its apical pole. We attempted to identify the SNAREs involved in zymogen granule
      exocytosis. Antibodies against syntaxins 2 and 3, SNAP-23 and VAMP 8, and the
      corresponding recombinant SNAREs, inhibited amylase secretion from streptolysin O
      permeabilised acini; other anti-SNARE antibodies and SNAREs had no effect.
      Botulinum neurotoxin C, which cleaved syntaxin 2 and (to a lesser extent)
      syntaxin 3, but not syntaxins 4, 7 or 8, also inhibited exocytosis. We propose
      that syntaxin 2, SNAP-23 and VAMP 8 mediate primary granule-plasma membrane
      fusion. Syntaxin 3 may be involved in secondary granule-granule fusion.

PMID- 17544373
TI  - The induction of H3K9 methylation by PIWIL4 at the p16Ink4a locus.
AB  - The field of epigenetics has made progress by the identification of the small RNA
      mediated epigenetic modification. However, little is known about the key
      proteins. Here, we report that the human PIWI-like family is a candidate protein
      that is involved in the pathway responsible for chromatin remodeling. The PIWI
      like family proteins, expressed as the Flag-fusion proteins, formed a bulky body
      and localized to the nuclear periphery. Transient transfection of PIWI-like 4
      (PIWIL4), only member of the PIWI-like family that was ubiquitously expressed in
      human tissues, induced histone H3 lysine 9 methylation at the p16(Ink4a) (CDKN2A)
      locus. The elevated level of histone methylation resulted in the downregulation
      of the p16(Ink4a) gene. These results suggest PIWIL4 plays important roles in the
      chromatin-modifying pathway in human somatic cells.

PMID- 17544374
TI  - Insights from modeling the 3D structure of NAD(P)H-dependent D-xylose reductase
      of Pichia stipitis and its binding interactions with NAD and NADP.
AB  - NAD(P)H-dependent d-xylose reductase is a homodimeric oxidoreductase that belongs
      to the aldo-keto reductase superfamily. The enzyme has the special function to
      catalyze the first step in the assimilation of xylose into yeast metabolic
      pathways. Performing this function via reducing the open chain xylose to xylitol,
      the xylose reductase of Pichia stipitis is one of the most important enzymes that
      can be used to construct recombinant Saccharomyces cerevisiae strain for
      utilizing xylose and producing alcohol. To investigate into the interaction
      mechanism of the enzyme with its ligand NAD and NADP, the 3D structure was
      developed for the NAD(P)H-dependent d-xylose reductase from P. stipitis. With the
      3D structure, the molecular docking operations were conducted to find the most
      stable bindings of the enzyme with NAD and NADP, respectively. Based on these
      results, the binding pockets of the enzyme for NAD and NADP have been explicitly
      defined. It has been found that the residues in forming the binding pockets for
      both NAD and NADP are almost the same and mainly hydrophilic. These findings may
      be used to guide mutagenesis studies, providing useful clues to modify the enzyme
      to improve the utilization of xylose for producing alcohol. Also, because human
      aldose reductases have the function to reduce the open chain form of glucose to
      sorbitol, a process physiologically significant for diabetic patients at the time
      that their blood glucose levels are elevated, the information gained through this
      study may also stimulate the development of new strategies for therapeutic
      treatment of diabetes.

PMID- 17544375
TI  - Endothelial cells are activated by angiopoeitin-1 gene transfer and produce
      coordinated sprouting in vitro and arteriogenesis in vivo.
AB  - RATIONAL AND OBJECTIVES: Activation of fully differentiated vascular cells using
      angiogenic genes can lead to phenotypic changes resulting in formation of new
      blood vessels. We tested whether Ang-1 gene transfer to endothelial cells (EC)
      activates these cells. METHODS AND RESULTS: EC and SMC were transduced using
      retroviral or adenoviral vectors to produce Ang-1 or vascular endothelial growth
      factor (VEGF). EC Tie-2 receptor was phosphorilated by autologous secretion of
      Ang-1. Transduced EC and SMC sprouting capacity was tested using collagen
      embedded spheroids assay and capacity to produce arteriogenesis was tested in a
      hind limb model of ischemia. EC expressing Ang-1 in the presence of SMC
      expressing VEGF exhibited high levels of sprouting of the two cell types. Flow
      and numbers of arteries were increased after transduced cells implantation in
      vivo. CONCLUSIONS: Autologous secretion of Ang-1 by transduced EC resulted in Tie
      2 activation and in the presence of SMC expressing VEGF resulted in coordinated
      sprouting in vitro and increase in flow and number of arteries in vivo.

PMID- 17544376
TI  - The reactivity of ortho-methoxy-substituted catechol radicals with sulfhydryl
      groups: contribution for the comprehension of the mechanism of inhibition of
      NADPH oxidase by apocynin.
AB  - Redox processes are involved in the mechanism of action of NADPH oxidase
      inhibitors such as diphenyleneiodonium and apocynin. Here, we studied the
      structure-activity relationship for apocynin and analogous ortho-methoxy
      substituted catechols as inhibitors of the NADPH oxidase in neutrophils and their
      reactivity with peroxidase. Aiming to alter the reduction potential, the ortho
      methoxy-catechol moiety was kept constant and the substituents at para position
      related to the hydroxyl group were varied. Two series of compounds were employed:
      methoxy-catechols bearing electron-withdrawing groups (MC-W) such as apocynin,
      vanillin, 4-nitroguaiacol, 4-cyanoguaiacol, and methoxy-catechol bearing electron
      donating groups (MC-D) such as 4-methylguaiacol and 4-ethylguaiacol. We found
      that MC-D were weaker inhibitors compared to MD-W. Furthermore, the radicals
      generated by oxidation of MC-W via MPO/H(2)O(2), but not for MC-D, were able to
      oxidize glutathione (GSH) as verified by the formation of thiyl radicals,
      depletion of GSH, and recycling of the ortho-methoxy-catechols during their
      oxidations. The capacity of oxidizing sulfhydryl (SH) groups was also verified
      when ovalbumin was incubated with MC-W, but not for MC-D. Since the effect of
      apocynin has been correlated with inactivation of the cytosolic fractions of the
      NADPH oxidase complex and its oxidation during the inhibitory process develops a
      special role in this process, we suggest that the close relationship between the
      reactivity of the radicals of MC-W compounds with thiol groups and their efficacy
      as NADPH oxidase inhibitor could be the chemical pathway behind the mechanism of
      action of apocynin and should be taken into account in the design of new and
      specific NADPH oxidase inhibitors.

PMID- 17544377
TI  - Change of drug excretory pathway by CCl4-induced liver dysfunction in rat.
AB  - Liver dysfunction affects the pharmacokinetics of drugs. The liver plays an
      important role in drug excretion as well as drug metabolism and pharmacokinetics.
      In the present study, the relationship between changes in the cefmetazole (CMZ)
      excretory pathway and the degree of liver dysfunction induced by CCl(4) treatment
      was investigated. CMZ is mainly excreted as an unchanged form in feces in control
      rats. Depending on the serum levels of aspartate aminotransferase (AST) and
      alanine aminotransferase (ALT), urinary CMZ excretion was increased, whereas
      fecal CMZ excretion was decreased in rat with liver dysfunction. The AUC of CMZ
      in rats with severe liver dysfunction was approximately 2-fold higher than that
      in control rats. Since drug transporters could be involved in drug excretion,
      changes in the expression of representative hepatic drug transporters in liver
      dysfunction were investigated by rat DNA microarray. Basolateral solute carrier
      transporters such as Ntcp, Oct1, and Oatp2 were decreased and basolateral ATP
      binding cassette transporters such as Mrp3 and Mrp4 were increased by the CCl(4)
      treatment. On the other hand, canalicular Mrp2 and Bsep were decreased, but Mdr1
      was increased. However, the transporter system for CMZ has not been identified
      yet. In conclusion, we clarified that the fecal and urinary excretory profiles of
      CMZ were changed clearly depending on the serum AST and ALT levels in liver
      dysfunction. The changes in the CMZ excretory pathway might be responsible for
      the changes in the expression of drug transporters.

PMID- 17544378
TI  - The effects of prolonged stress and APOE genotype on memory and cortisol in older
      adults.
AB  - BACKGROUND: Chronic elevations in cortisol associated with prolonged stress have
      been associated with memory loss, as has the apolipoprotein E gene (APOE
      epsilon4) genotype. Combined effects of stress and APOE status on memory and
      cortisol in humans have not been studied. METHODS: A semistructured interview
      with standardized scoring was used to measure stress level and univariate
      analysis of variance to assess effects of stress and APOE-epsilon4 status on
      memory and salivary cortisol in 91 nondemented subjects (mean age 78.8 years).
      RESULTS: Low-stress subjects performed better than high-stress subjects on
      delayed recall of stories (p = .04), word lists (p = .02), and visual designs (p
      = .04). APOE-epsilon4-negative subjects obtained better scores than epsilon4
      positive subjects on immediate (p = < .01) and delayed (p < .01) recall of visual
      designs. Significant stress by APOE-epsilon4 interaction effects on memory (p =
      .03) and cortisol (p < .01) resulted from consistently worse memory and higher
      cortisol concentrations in the high stress, epsilon4-positive group. CONCLUSIONS:
      These findings are consistent with a model in which prolonged exposure of older,
      nondemented individuals to stress in the presence of an epsilon4 allele leads to
      memory decline. Further studies will assess whether stress and APOE-epsilon4
      interact to increase the risk of developing Alzheimer's disease.

PMID- 17544379
TI  - Interactive effects of sex and 5-HTTLPR on mood and impulsivity during tryptophan
      depletion in healthy people.
AB  - BACKGROUND: Serotonin (5-HT) plays a central role in mood regulation and
      impulsivity. We studied whether healthy men and women react differently on mood
      and impulsivity measures during acute tryptophan depletion (ATD). We also studied
      the relative contribution of a functional length triallelic polymorphism in the
      promoter region of the serotonin transporter, designated 5-HTTLPR, to the
      behavioral responses to ATD. METHODS: Thirty-nine men and 44 women participated
      in a randomized, double-blind, parallel group ATD study. Behavioral measures of
      impulsivity and mood were obtained. RESULTS: During ATD, women reported mood
      reduction and showed a cautious response style, which is commonly associated with
      depression. Men showed an impulsive response style and did not report mood
      reduction. The 5-HTTLPR influenced the mood response to ATD in women.
      CONCLUSIONS: Healthy men became more impulsive, whereas healthy women showed mood
      reduction in response to ATD. This suggests that 5-HT could be one mechanism
      contributing to the sex differences in the prevalence of mood and impulsivity
      disorders. The influence of 5-HTTLPR on mood responses in women further
      substantiates the relevance of this variant in the pathophysiology of at least a
      subgroup of patients with major depressive disorder.

PMID- 17544380
TI  - Evidence for a susceptibility locus on chromosome 10p15 in early-onset obsessive
      compulsive disorder.
AB  - BACKGROUND: The goal of this study was to identify chromosomal regions likely to
      contain susceptibility loci for obsessive-compulsive disorder (OCD). METHODS: We
      conducted a genome-wide linkage scan, with average marker spacing less than 10
      centimorgans (cM), in 121 subjects from 26 families ascertained through probands
      with early-onset OCD. Best estimate lifetime psychiatric diagnoses were based on
      semistructured interviews and all other available sources of information.
      Parametric and nonparametric linkage analyses were conducted with GENEHUNTER+ and
      Allegro. Family-based association analyses were done using 35 single nucleotide
      polymorphisms (SNPs) in the 10p15 region. RESULTS: The maximum nonparametric log
      of odds (NLOD) score was 2.43 on chromosome 10p15 at position 4.37. When data
      from our first genome scan were added to data from this scan, the maximum NLOD
      score in the 10p15 region was 1.79. Association was detected on 10p15 with three
      adjacent SNPs, including the amino acid variant rs2271275 in the 3' region of
      adenosine deaminase acting on RNA 3 (ADAR3) (p < .05). CONCLUSIONS: The results
      provide suggestive evidence for linkage on chromosome 10p15. Evidence for
      association in the linkage region was found with three markers in the 3' end of
      ADAR3. Limitations include the lack of significant linkage and association
      findings when corrected for multiple testing.

PMID- 17544381
TI  - Depression, antidepressants, and plasma amyloid beta (Beta) peptides in those
      elderly who do not have cardiovascular disease.
AB  - BACKGROUND: Low plasma amyloid-beta peptide 42 (Abeta42) is associated with
      depressive symptoms independently of cardiovascular disease (CVD) in the elderly.
      It is critical to investigate whether antidepressants modify this relationship.
      METHODS: We evaluated 324 elders without CVD in a cross-sectional study.
      Depression was evaluated with the Center for Epidemiological Studies Depression
      (CES-D) scale. Antidepressants were documented. Plasma Abeta40 and Abeta42 were
      measured. RESULTS: In the absence of CVD, those with depression had lower plasma
      Abeta42 (median: 13.7 vs. 18.8 pg/mL, p = .003) than those without. Depressed
      subjects on antidepressant treatment had a lower concentration of plasma Abeta40
      (median: 97.8 vs. 133.5 pg/mL, p = .008), but not Abeta42, than those without the
      treatment. Multivariate logistic regression showed that antidepressant use did
      not influence the relationship between depression and low plasma Abeta42 (odds
      ratio = .55; 95% CI = .33, .90; p = .02) after adjusting for confounders, but its
      use interacted with plasma Abeta40 in the model. CONCLUSIONS: Lower concentration
      of plasma Abeta42 is associated with depression in the absence of CVD that is not
      related to the antidepressant use by those subjects. Prospective studies are
      needed to determine whether depression associated with low plasma Abeta42
      predicts the onset of Alzheimer's disease.

PMID- 17544382
TI  - Evolving knowledge of sex differences in brain structure, function, and
      chemistry.
AB  - Clinical and epidemiologic evidence demonstrates sex differences in the
      prevalence and course of various psychiatric disorders. Understanding sex
      specific brain differences in healthy individuals is a critical first step toward
      understanding sex-specific expression of psychiatric disorders. Here, we evaluate
      evidence on sex differences in brain structure, chemistry, and function using
      imaging methodologies, including functional magnetic resonance imaging (fMRI),
      positron emission tomography (PET), single photon emission computed tomography
      (SPECT), and structural magnetic resonance imaging (MRI) in mentally healthy
      individuals. MEDLINE searches of English-language literature (1980-November 2006)
      using the terms sex, gender, PET, SPECT, MRI, fMRI, morphometry, neurochemistry,
      and neurotransmission were performed to extract relevant sources. The literature
      suggests that while there are many similarities in brain structure, function, and
      neurotransmission in healthy men and women, there are important differences that
      distinguish the male from the female brain. Overall, brain volume is greater in
      men than women; yet, when controlling for total volume, women have a higher
      percentage of gray matter and men a higher percentage of white matter. Regional
      volume differences are less consistent. Global cerebral blood flow is higher in
      women than in men. Sex-specific differences in dopaminergic, serotonergic, and
      gamma-aminobutyric acid (GABA)ergic markers indicate that male and female brains
      are neurochemically distinct. Insight into the etiology of sex differences in the
      normal living human brain provides an important foundation to delineate the
      pathophysiological mechanisms underlying sex differences in neuropsychiatric
      disorders and to guide the development of sex-specific treatments for these
      devastating brain disorders.

PMID- 17544383
TI  - Age modulates the nitric oxide system response in the ischemic cerebellum.
AB  - To determine whether age influences the nitric oxide system response to ischemia
      in the cerebellum, we have analyzed the levels of nitrogen oxides (NOx) and the
      expression of the different nitric oxide synthase isoforms (NOS) in mature adult
      (4-5 months old) and aged rats (24-27 months old) subjected to a transient global
      ischemia/reperfusion (I/R) model. We also analyzed the nitrated proteins and the
      glial fibrillary acidic protein (GFAP) expression. NOx concentration in adult
      rats, which more than doubled the values found in the aged rats, decreased after
      the ischemia and reperfusion. However, in the aged animals, these NOx levels did
      not significantly change after I/R. Constitutive isoforms were first down
      regulated in the ischemic period, in both adult and aged animals. However, after
      6 h of reperfusion, these isoforms were up-regulated, but only in aged rats.
      After I/R, iNOS was up-regulated in adults but down-regulated in the aged rats.
      Hence, after an episode of transient global ischemia and reperfusion, the aged
      cerebellum maintains a balanced NO production, silencing the iNOS isoform and
      inducing a weak expression of nNOS and eNOS; this allows NO physiological
      functions while avoiding possible undesirable effects such as the nitrative
      damage or astrocyte activation.

PMID- 17544384
TI  - Behavioural and neurophysiological correlates of bivalent and univalent responses
      during task switching.
AB  - A hallmark of human behaviour is its flexibility. In any given circumstance there
      is typically a range of possible responses that could be selected. In the current
      study participants were presented with stimulus displays that afforded two simple
      cognitive tasks and were required to switch predictably between them. The
      judgements for each task were either uniquely mapped onto separate effectors
      (univalent conditions) or else mapped onto shared effectors (bivalent condition).
      The results demonstrated that whilst behavioural switch costs were similar across
      the mapping conditions, these conditions differed in the patterns of brain
      activity observed during task preparation and early visual processing of the
      target. Specifically, a cue-locked switch-related late frontal negativity was
      present over frontal sensors for the bivalent condition only, and a target-locked
      N1 over occipital sensors was larger in the bivalent condition than the univalent
      conditions. In contrast, a switch-related target-locked P3b component was common
      to all mapping conditions. These findings are discussed with respect to
      differences in processing demands for switching between tasks with bivalent
      versus univalent responses.

PMID- 17544385
TI  - Active versus passive cocaine administration: differences in the neuroadaptive
      changes in the brain dopaminergic system.
AB  - There is considerable evidence that chronic exposure to cocaine is associated
      with low striatal dopamine D2 receptor availability. In the present study we
      wished to determine whether neuroadaptive changes in densities of D2 receptors
      were due to direct pharmacological actions of cocaine or they reflected
      motivational states that were present when cocaine injection depended on active
      drug-seeking behavior and whether these changes were related to the actual
      expression of D2 mRNA. To achieve this goal we utilized a "yoked" procedure in
      which rats were tested simultaneously in groups of three, with only one rat
      actively self-administering cocaine while the other two received yoked injections
      of either cocaine or saline. Only passively administered cocaine produced a
      decrease in dopamine D2 receptor levels in the anterior and central regions of
      caudate/putamen, and both the shell and core of the nucleus accumbens, as
      measured by in vitro quantitative autoradiography. In contrast, examination of D2
      receptor gene expression using in situ hybridization analysis revealed that there
      was an increase in D2 receptor mRNA levels in the ventral tegmental area of rats
      actively self-administered cocaine. We conclude that the reductions in striatal
      D2 receptor densities may be related to the chronic administration of cocaine per
      se and not to the motivated process of reinforced responding. Our results also
      suggest that increases in D2 receptor mRNA levels in limbic regions do not
      necessarily result in increased receptor densities and these changes likely
      reflect motivational states that were present when cocaine injection dependent on
      active drug self-administration.

PMID- 17544386
TI  - Biochemistry of protein tyrosine nitration in cardiovascular pathology.
AB  - Several pathologies of the cardiovascular system are associated with an augmented
      production of nitric oxide and/or superoxide-derived oxidants and/or alteration
      in the antioxidant detoxification pathways that lead to nitroxidative stress. One
      important consequence of these reactive intermediates at the biochemical level is
      the nitration of protein tyrosines, which is performed through either of two of
      the relevant nitration pathways that operate in vivo, namely peroxynitrite and
      heme peroxidase-dependent nitration. Proteins nitrated at tyrosine residues have
      been detected in several compartments of the cardiovascular system. In this
      review a selection of nitrated proteins in plasma (fibrinogen, plasmin, Apo-1),
      vessel wall (Apo-B, cyclooxygenase, prostaglandin synthase, Mn-superoxide
      dismutase) and myocardium (myofibrillar creatine kinase, alpha-actinin,
      sarcoplasmic reticulum Ca(2+) ATPase) are analyzed in the context of
      cardiovascular disease. Nitration of tyrosine can affect protein function, which
      could directly link nitroxidative stress to the molecular alterations found in
      disease. While some proteins are inactivated by nitration (e.g. Mn-SOD) others
      undergo a gain-of-function (e.g. fibrinogen) that can have an ample impact on the
      pathophysiology of the cardiovascular system. Nitrotyrosine is also emerging as a
      novel independent marker of cardiovascular disease. Pharmacological strategies
      directed towards inhibiting protein nitration will assist to shed light on the
      relevance of this post-translational modification to human cardiovascular
      pathology.

PMID- 17544388
TI  - Oxidative mechanisms at rest and during exercise.
AB  - Carbohydrates (CHO) and lipids provide the amount of energy required for physical
      and chemical reactions inside the human body. The various constraints the body
      has to resolve explain the use of these two substrates, catabolized via distinct
      pathways to one common final reaction. In the classic model, three main
      organs/tissues for substrate fluxes (liver, adipose tissue and skeletal muscle)
      and one organ regulating main reactions by adaptation of hormonal secretions
      (endocrine pancreas) are described. From this point of view, the only
      interactions between CHO and lipid metabolisms are mediated by glycaemic changes
      via insulin/glucagon ratio (IGR). However, according to recent advances, this
      concept seems to have a limited validity as it does take into account neither the
      many other interactions between CHO and lipid metabolism that are likely to occur
      in addition to the coarse control by IGR, nor the long-term regulation of energy
      balance, whose description began with the discovery of leptin. Moreover, it does
      not include the effects of energy expenditure. Therefore, this review focuses on
      three topics: (i) describe interactions between CHO and lipid metabolism at the
      level of each tissue and organ implied, via hormonal signaling as well as direct
      action of nutrients, (ii) integrate fluxes of substrates and signals between
      those tissues at rest in a global view of the metabolism taking into account
      short-term and long-term regulating factors and (iii) describe separately, to
      avoid confusion or extrapolation, the short-term and long-term influence of
      exercise on these regulation loops.

PMID- 17544387
TI  - Inhaled NO as a therapeutic agent.
AB  - In 1991, Frostell and colleagues reported that breathing low concentrations of
      nitric oxide (NO) decreased pulmonary artery pressure (PAP) in awake lambs with
      experimental pulmonary hypertension (PH) [Frostell C, Fratacci MD, Wain JC, Jones
      R, Zapol WM. Inhaled nitric oxide. A selective pulmonary vasodilator reversing
      hypoxic pulmonary vasoconstriction. Circulation 1991;83:2038-47]. Subsequently,
      efforts of multiple research groups studying animals and patients led to approval
      of inhaled NO by the US Food and Drug Administration in 1999 and the European
      Medicine Evaluation Agency and European Commission in 2001. Inhaled NO is
      currently indicated for the treatment of term and near-term neonates with
      hypoxemia and PH. Since regulatory approval, several studies have suggested that
      NO inhalation can prevent chronic lung disease in premature infants. In addition,
      unanticipated systemic effects of inhaled NO may lead to treatments for a variety
      of disorders including ischemia-reperfusion injury. This review summarizes the
      pharmacology and physiological effects of breathing NO. The application of
      inhaled NO to hypoxemic neonates with PH is discussed including recent studies
      exploring the use of inhaled NO to prevent bronchopulmonary dysplasia in
      premature infants. This review also highlights the application of inhaled NO to
      treat adults with cardiopulmonary disease, strategies to augment the efficacy of
      inhaled NO, and potential applications of the systemic effects of the gas.

PMID- 17544389
TI  - Cross-reactivity of epoetin alfa and darbepoetin alfa with two
      immunochemiluminometric erythropoietin assays.

PMID- 17544390
TI  - Improving cluster visualization in self-organizing maps: application in gene
      expression data analysis.
AB  - Cluster analysis is one of the crucial steps in gene expression pattern (GEP)
      analysis. It leads to the discovery or identification of temporal patterns and
      coexpressed genes. GEP analysis involves highly dimensional multivariate data
      which demand appropriate tools. A good alternative for grouping many
      multidimensional objects is self-organizing maps (SOM), an unsupervised neural
      network algorithm able to find relationships among data. SOM groups and maps them
      topologically. However, it may be difficult to identify clusters with the usual
      visualization tools for SOM. We propose a simple algorithm to identify and
      visualize clusters in SOM (the RP-Q method). The RP is a new node-adaptive
      attribute that moves in a two dimensional virtual space imitating the movement of
      the codebooks vectors of the SOM net into the input space. The Q statistic
      evaluates the SOM structure providing an estimation of the number of clusters
      underlying the data set. The SOM-RP-Q algorithm permits the visualization of
      clusters in the SOM and their node patterns. The algorithm was evaluated in
      several simulated and real GEP data sets. Results show that the proposed
      algorithm successfully displays the underlying cluster structure directly from
      the SOM and is robust to different net sizes.

PMID- 17544391
TI  - FGF9 regulates early hypertrophic chondrocyte differentiation and skeletal
      vascularization in the developing stylopod.
AB  - Gain-of-function mutations in fibroblast growth factor (FGF) receptors result in
      chondrodysplasia and craniosynostosis syndromes, highlighting the critical role
      for FGF signaling in skeletal development. Although the FGFRs involved in
      skeletal development have been well characterized, only a single FGF ligand,
      FGF18, has been identified that regulates skeletal development during
      embryogenesis. Here we identify Fgf9 as a second FGF ligand that is critical for
      skeletal development. We show that Fgf9 is expressed in the proximity of
      developing skeletal elements and that Fgf9-deficient mice exhibit rhizomelia (a
      disproportionate shortening of proximal skeletal elements), which is a prominent
      feature of patients with FGFR3-induced chondrodysplasia syndromes. Although Fgf9
      is expressed in the apical ectodermal ridge in the limb bud, we demonstrate that
      the Fgf9-/- limb phenotype results from loss of FGF9 functions after formation of
      the mesenchymal condensation. In developing stylopod elements, FGF9 promotes
      chondrocyte hypertrophy at early stages and regulates vascularization of the
      growth plate and osteogenesis at later stages of skeletal development.

PMID- 17544392
TI  - Interaction of nicotinic and histamine H(3) systems in the radial-arm maze
      repeated acquisition task.
AB  - Nicotinic systems have been found in a variety of studies to play important roles
      in cognitive function. Nicotinic involvement in different aspects of cognitive
      function such as learning vs. memory may differ. We have found in rats that the
      spatial repeated acquisition task in the radial-arm maze is significantly
      improved by low doses of the nicotinic receptor antagonist mecamylamine, the
      atypical nicotinic receptor ligand lobeline, as well as the alpha7 nicotinic
      receptor agonist ARR-17779. Interestingly, nicotine in the same dose range that
      improves working memory in the win-shift radial maze task was not effective in
      improving repeated acquisition performance. Nicotinic systems interact with a
      variety of other neural systems. Differential involvement of these extended
      effects with learning vs. memory may help explain differential effects of
      nicotinic drugs with these cognitive functions. Histamine H(3) receptor
      antagonists have been shown by some studies to improve cognitive function, but
      others have not found this effect and some have found impairment. Nicotine
      stimulates the release of histamine. This effect may counter other cascading
      effects of nicotine in the performance of learning and memory tasks. A specific
      test of this hypothesis involves our study of nicotine (0.1-0.4 mg/kg)
      interactions with the histamine H(3) receptor antagonist thioperamide (2.5-10
      mg/kg) on learning memory in the repeated acquisition test in the radial-arm
      maze. The highest dose of thioperamide tested caused a significant choice
      accuracy impairment, which was most evident during the later portions of the
      learning curve. The highest dose of nicotine did not change overall errors but
      did cause a significant impairment in learning over trials. The choice accuracy
      impairment induced by thioperamide was significantly attenuated by nicotine (0.4
      mg/kg). The learning impairment caused by the highest dose of nicotine was
      significantly attenuated by thioperamide. Thioperamide also caused a slowing of
      response, an effect, which was attenuated by nicotine co-administration. The
      repeated acquisition test can help differentiate acute drug effects on learning.
      Nicotine and thioperamide effectively reversed each other's choice accuracy
      impairment even though each by itself impaired accuracy.

PMID- 17544393
TI  - Antioxidative effects of azelnidipine on mesangial cell proliferation induced by
      highly concentrated insulin.
AB  - Insulin resistance combined with hyperinsulinemia is involved in the generation
      of oxidative stress. There is known to be a relationship between increased
      production of reactive oxygen species and the diverse pathogenic mechanisms
      involved in diabetic vascular complications including nephropathy. The present
      study found that high doses of insulin affect mesangial cell proliferation
      through the generation of intracellular reactive oxygen species and the
      activation of cell signaling pathways. We also examined whether azelnidipine, a
      dihydropyridine-based calcium antagonist with established antioxidant activity,
      has the potential to inhibit mesangial cell proliferation. Cell proliferation was
      increased in a dose-dependent manner by high doses of insulin (0.1-10 microM),
      but was inhibited by 0.1 microM azelnidipine. Phosphorylation of extracellular
      signal-regulated kinase (ERK)-1/2 was found to be increased by insulin in a dose
      dependent manner (0.1-10 microM). This increased phosphorylation of ERK-1/2 was
      inhibited by treatment with 0.1 microM azelnidipine. Intracellular oxidative
      stress was also increased by insulin stimulation in a dose-dependent manner (0.01
      10 microM), and 0.1 microM azelnidipine was found to block intracellular reactive
      oxygen species production more effectively than 0.1 microM nifedipine. The
      NAD(P)H oxidase inhibitor, apocynin (0.01-0.1 microM), prevented insulin-induced
      mesangial cell proliferation. Taken together, these results suggest that
      azelnidipine inhibits insulin-induced mesangial cell proliferation by inhibiting
      the production of reactive oxygen species. Given these pharmacological
      characteristics, azelnidipine may have the potential to protect against the onset
      of diabetic nephropathy and slow its progression.

PMID- 17544394
TI  - 'Working' cardiomyocytes exhibiting plateau action potentials from human placenta
      derived extraembryonic mesodermal cells.
AB  - The clinical application of cell transplantation for severe heart failure is a
      promising strategy to improve impaired cardiac function. Recently, an array of
      cell types, including bone marrow cells, endothelial progenitors, mesenchymal
      stem cells, resident cardiac stem cells, and embryonic stem cells, have become
      important candidates for cell sources for cardiac repair. In the present study,
      we focused on the placenta as a cell source. Cells from the chorionic plate in
      the fetal portion of the human placenta were obtained after delivery by the
      primary culture method, and the cells generated in this study had the Y sex
      chromosome, indicating that the cells were derived from the fetus. The cells
      potentially expressed 'working' cardiomyocyte-specific genes such as cardiac
      myosin heavy chain 7beta, atrial myosin light chain, cardiac alpha-actin by gene
      chip analysis, and Csx/Nkx2.5, GATA4 by RT-PCR, cardiac troponin-I and connexin
      43 by immunohistochemistry. These cells were able to differentiate into
      cardiomyocytes. Cardiac troponin-I and connexin 43 displayed a discontinuous
      pattern of localization at intercellular contact sites after cardiomyogenic
      differentiation, suggesting that the chorionic mesoderm contained a large number
      of cells with cardiomyogenic potential. The cells began spontaneously beating 3
      days after co-cultivation with murine fetal cardiomyocytes and the frequency of
      beating cells reached a maximum on day 10. The contraction of the cardiomyocytes
      was rhythmical and synchronous, suggesting the presence of electrical
      communication between the cells. Placenta-derived human fetal cells may be useful
      for patients who cannot supply bone marrow cells but want to receive stem cell
      based cardiac therapy.

PMID- 17544395
TI  - Oligodendrocyte ablation affects the coordinated interaction between granule and
      Purkinje neurons during cerebellum development.
AB  - Oligodendrocytes (OLs) are the glial cells of the central nervous system (CNS)
      classically known to be devoted to the formation of myelin sheaths around most
      axons of the vertebrate brain. We have addressed the role of these cells during
      cerebellar development, by ablating OLs in vivo. Previous analyses had indicated
      that OL ablation during the first six postnatal days results into a striking
      cerebellar phenotype, whose major features are a strong reduction of granule
      neurons and aberrant Purkinje cells development. These two cell types are highly
      interconnected during cerebellar development through the production of molecules
      that help their proliferation, differentiation and maintenance. In this article,
      we present data showing that OL ablation has major effects on the physiology of
      Purkinje (PC) and granule cells (GC). In particular, OL ablation results into a
      reduction of sonic hedgehog (Shh), Brain Derived Neurotrophic Factor (BDNF), and
      Reelin (Rln) expression. These results indicate that absence of OLs profoundly
      alters the normal cerebellar developmental program.

PMID- 17544396
TI  - Protective effects of myricetin and related flavonols against A2E and light
      mediated-cell death in bovine retinal primary cell culture.
AB  - The present study was performed to investigate the effect of flavonols, namely
      myricetin and structurally related quercetin and kaempferol against A2E and blue
      light-induced photoreceptors death in primary retinal cell cultures. Primary
      retinal cell cultures were prepared from bovine retinas. Fourteen-day-old
      cultures were pretreated with different concentrations of myricetin, quercetin,
      kaempferol (1-40 microM) for 24 h, then treated with 30 microM of A2E or exposed
      to blue-actinic light for 20 h. Green nucleic acid stain assay was used to
      evaluate cell death. Photoreceptor and bipolar cells were immunolabeled with
      specific antibodies and were counted using automated microscope imaging and image
      based cell counting software. Twenty hours exposure to blue light induced
      approximately 75% death of photoreceptors in bovine retinal cell cultures.
      Myricetin protected 100% of photoreceptors against blue-light-mediated damage
      with an EC(50) of 9+/-0.7 microM. Quercetin resulted in a maximum of 15%
      protection against light damage, and kaempferol was inactive. A2E induced
      photoreceptor and bipolar cell death in a concentration-dependent manner with
      EC(50) of 25 microM for photoreceptors and 31 microM for bipolar cells.
      Myricetin, quercetin and kaempferol protected against A2E-induced photoreceptors
      and bipolar cells death with EC(50) values of 2+/-0.3 microM, 2+/-0.3 microM, 5+/
      0.09 microM and 0.8+/-0.07 microM, 0.44+/-0.06 microM, 1+/-0.4 microM,
      respectively. Caspase-3 inhibitor (Z-DEVD-fmk) protected 42% photoreceptors and
      57% bipolar cells from A2E toxicity. In contrast, this inhibitor had no effect
      against light-induced photoreceptor damage. Despite the poor activity of
      quercetin and the inactivity of kaempferol against blue light, myricetin,
      quercetin and kaempferol exhibited approximately 100% protection against A2E
      toxicity. This suggests that light- and A2E-induced cell deaths are mediated
      through different pathways. These results suggest that myricetin functions as
      potent and effective neuroprotective agent for photoreceptor cells against A2E
      and light damage.

PMID- 17544397
TI  - Dorsal raphe nuclei integrate allostatic information evoked by depletion-induced
      sodium ingestion.
AB  - Structures of the lamina terminalis (LT) sense and integrate information
      reflecting the state of body water and sodium content. Output from the LT
      projects into a neural network that regulates body fluid balance. Serotonin (5
      HT) and the dorsal raphe nuclei (DRN) have been implicated in the inhibitory
      control of salt intake (i.e., sodium appetite). Signals arriving from the LT
      evoked by fluid depletion-induced sodium ingestion interact with this inhibitory
      serotonergic system. We investigated the role of neurons along the LT that
      directly project to the DRN. We analyzed the pattern of immunoreactivity (ir) of
      LT cells double-labeled for Fos (a marker of neural activity) and Fluorogold (FG;
      a retrograde tracer) following sodium depletion-induced sodium intake. Seven days
      after injection of FG into the DRN, sodium appetite was induced by furosemide
      injection and overnight access to only a low sodium diet (Furo-LSD) and distilled
      water. Twenty-four hours later, access to 0.3 M NaCl was given to depleted or
      sham-depleted rats and sodium intake was measured over the following 60 min.
      Ninety minutes after the termination of the intake test, the animals were
      perfused and their brains were processed for immunohistochemical detection of Fos
      and FG. Compared to sham-depleted animals there was a significantly greater
      number of Fos-/FG-ir double-labeled cells in the subfornical organ, the organum
      vasculosum of the lamina terminalis and the median preoptic nucleus in rats that
      ingested NaCl. Projections from the LT cells may contribute to inhibitory
      mechanisms involving 5-HT neurons in the DRN that limit the intake of sodium and
      prevent excess volume expansion.

PMID- 17544398
TI  - A gram-negative characteristic segment in Escherichia coli DnaK is essential for
      the ATP-dependent cooperative function with the co-chaperones DnaJ and GrpE.
AB  - We describe importance of the characteristic segment in ATPase domain of DnaK
      chaperone which is present in all gram-negative bacteria but is absent in all
      gram-positive bacteria. In vitro studies, ATPase activity, luciferase-refolding
      activity, and surface plasmon resonance analyses, demonstrated that a segment
      deletion mutant DnaKDelta74-96 became defective in the cooperation with the co
      chaperones DnaJ and GrpE. In addition, in vivo complementation assay showed that
      expression of DnaKDelta74-96 could not rescue the viability of Escherichia coli
      DeltadnaK mutant at 43 degrees C. Consequently, we suggest evolutionary
      significance for this DnaK ATPase domain segment in gram-negative bacteria
      towards the DnaK chaperone system.

PMID- 17544399
TI  - A Cre-loxP based system for studying horizontal gene transfer.
AB  - We have previously shown that DNA can be transferred to phagocytosing cells via
      the uptake of apoptotic cells. We report a model system that facilitates study of
      antigen presentation of genes transferred specifically via horizontal gene
      transfer. Constructs were generated encoding the LacZ gene or the influenza A
      nucleoprotein silenced by a STOP sequence flanked by two loxP sites. These
      reporter genes were demonstrated to be silent in donor cells and become activated
      after phagocytosis of Cre-expressing fibroblasts or macrophages. These results
      provide a model system for studying the influence of horizontally transferred
      antigens on activation of the immune system.

PMID- 17544400
TI  - Identification and expression-profiling of Xenopus tropicalis miRNAs including
      plant miRNA-like RNAs at metamorphosis.
AB  - Small RNAs (miR159-like RNAs) identical to some plant miR159s were found in
      Xenopus tropicalis miRNA cDNA libraries (30 miRNA families consisting of 75
      unique sequences). Preferential expression of this RNA species was found in
      neural tissues during development. A sequence matching to this RNA species was
      not found in the 21 available animal's genome databases, but its resembling
      sequences associated with transposons were found in the X. tropicalis database. A
      possibility of horizontal transfer of the miR159 genes from plants will be
      discussed. Expression profiles of other miRNA species at metamorphosis were shown
      by DNA array and/or Northern hybridization.

PMID- 17544401
TI  - Crystal structure of human wildtype and S581L-mutant glycyl-tRNA synthetase, an
      enzyme underlying distal spinal muscular atrophy.
AB  - Dominant mutations in the ubiquitous enzyme glycyl-tRNA synthetase (GlyRS),
      including S581L, lead to motor nerve degeneration. We have determined crystal
      structures of wildtype and S581L-mutant human GlyRS. The S581L mutation is
      approximately 50A from the active site, and yet gives reduced aminoacylation
      activity. The overall structures of wildtype and S581L-GlyRS, including the
      active site, are very similar. However, residues 567-575 of the anticodon-binding
      domain shift position and in turn could indirectly affect glycine binding via the
      tRNA or alternatively inhibit conformational changes. Reduced enzyme activity may
      underlie neuronal degeneration, although a dominant-negative effect is more
      likely in this autosomal dominant disorder.

PMID- 17544402
TI  - The heat shock protein 70 family: Highly homologous proteins with overlapping and
      distinct functions.
AB  - The human heat shock protein 70 (Hsp70) family contains at least eight homologous
      chaperone proteins. Endoplasmatic reticulum and mitochondria have their specific
      Hsp70 proteins, whereas the remaining six family members reside mainly in the
      cytosol and nucleus. The requirement for multiple highly homologous although
      different Hsp70 proteins is still far from clear, but their individual and tissue
      specific expression suggests that they are assigned distinct biological tasks.
      This concept is supported by the fact that mice knockout for different Hsp70
      genes display remarkably discrete phenotypes. Moreover, emerging data suggest
      that individual Hsp70 proteins can bring about non-overlapping and chaperone
      independent functions essential for growth and survival of cancer cells. This
      review summarizes our present knowledge of the individual members of human Hsp70
      family and elaborate on the functional differences between the cytosolic/nuclear
      representatives.

PMID- 17544403
TI  - Reoxygenation following hypoxia activates DNA-damage checkpoint signaling
      pathways that suppress cell-cycle progression in cultured human lymphocytes.
AB  - Cellular responses to DNA damage after hypoxia and reoxygenation (H/R) were
      examined in human lymphocytes. Cultured lymphocytes exposed to H/R showed a lower
      cytokinesis block proliferation index and a higher frequency of micronuclei in
      comparison to control cells. Western blots showed that H/R exposure induced p53
      expression; however, p21 and Bax expression did not increase, indicating that H/R
      did not affect p53 transactivational activity. Phosphorylation of p53 (Ser15),
      Chk1 (Ser345), and Chk2 (Thr68) was also observed, suggesting that H/R activates
      p53 through checkpoint signals. In addition, H/R exposure caused the
      phosphorylation and negative regulation of Cdc2 and Cdc25C, proteins that are
      involved in cell-cycle arrest at the G2/M checkpoint. The S-phase checkpoint,
      regulated by the ATM-p95/NBS1-SMC1 pathway, was also triggered in H/R-exposed
      lymphocytes. These results demonstrate that H/R exposure triggers checkpoint
      signaling and induces cell-cycle arrest in cultured human lymphocytes.

PMID- 17544404
TI  - Identification and characterization of Harobin, a novel fibrino(geno)lytic serine
      protease from a sea snake (Lapemis hardwickii).
AB  - A gene encoding a novel serine protease designated as Harobin is cloned and
      identified from a sea snake venom gland bacteriophage T7 library. It has 265
      amino acids and shares 50-70% similarity to terrestrial snake serine proteases.
      In addition to the 12 conservative Cys, it has three more Cys residues that may
      contribute to its higher enzymatic stability. Harobin is expressed in Pichia
      pastoris and purified. Recombinant Harobin exhibits an amidolytic activity, and
      specifically degrades Aalpha, Bbeta-chain of fibrinogen. It functions as a
      defibrase both in vitro and in vivo, and reduces thrombosis. Harobin prolongs the
      coagulation time and the bleeding time of mice and reduces the fibrinogen levels
      of rats as well. Meanwhile, intravenous injection of Harobin leads to the
      reduction of blood pressure in SHR rats. It results from the ability of Harobin
      that cleaves angiotensin I and release bradykinin from plasma kininogen in vitro
      and in vivo. These data suggest that Harobin is a novel defibrase and has a
      potential to be an agent for the therapy of thrombosis and hypertension.

PMID- 17544405
TI  - Caspase-3-mediated cleavage of Akt: involvement of non-consensus sites and
      influence of phosphorylation.
AB  - Here, we show for the first time that Akt1 is cleaved in vitro at the caspase-3
      consensus site DQDD(456) downward arrow SM. Our data suggest QEEE(116) downward
      arrow E(117) downward arrow MD, EEMD(119) downward arrow, TPPD(453) downward
      arrow QD and DAKE(398) downward arrow IM as novel non-consensus caspase-3
      cleavage sites. More importantly, we demonstrate that phosphorylation of Akt1
      modulates its cleavage in a site-specific manner: Resistance to cleavage at site
      DAKE(398) (within the kinase domain) in response to phosphorylation suggests a
      possible mechanism by which the anti-apoptotic role of Akt1 is regulated. Our
      result is important in biological models which rely on Akt1 for cell survival.

PMID- 17544406
TI  - Chimeric phosphofructokinases involving exchange of the N- and C-terminal halves
      of mammalian isozymes: implications for ligand binding sites.
AB  - Two phosphofructokinase (PFK) chimeras were constructed by exchanging the N- and
      C-terminal halves of the mammalian M- and C-type isozymes, to investigate the
      contribution of each terminus to the catalytic site and the fructose-2,6
      P(2)/fructose-1,6-P(2) allosteric site. The homogeneously-purified chimeric
      enzymes organized into tetramers, and exhibited kinetic properties for fructose-6
      P and MgATP similar to those of the native enzyme that furnished the N-terminal
      domain in each case, whereas their fructose-2,6-P(2) activatory characteristics
      coincided with those of the isozyme that provided the C-terminal half. This
      reflected the role of each domain in the formation of the corresponding binding
      site. Grafting the N-terminus of PFK-M onto the C-terminus of the fructose-1,6
      P(2) insensitive PFK-C restored transduction of this signal to the catalytic
      site, which significance is also discussed.

PMID- 17544407
TI  - Protease signalling in cell death: caspases versus cysteine cathepsins.
AB  - Proteases were, for a long time, mainly considered as protein degrading enzymes.
      However, in the last decade this view has changed dramatically, and the focus is
      now on proteases as signalling molecules. One of the best examples is apoptosis,
      the major mechanism used by eukaryotes to remove superfluous, damaged and
      potentially dangerous cells, in which a number of proteases have been found to
      play a central role. Of these the caspases have been considered to be the major
      players. However, more recently, other proteases have been increasingly suggested
      as being important in apoptosis, in particular the cysteine cathepsins. In this
      review the roles of caspases and cysteine cathepsins in apoptosis signalling are
      compared and discussed.

PMID- 17544408
TI  - Contributions of Zn(II)-binding to the structural stability of endostatin.
AB  - Endostatin has a compact structure with a Zn(II)-binding site (His1, His3, His11,
      and Asp76) at the N-terminus. In this study, the effects of Zn(II)-binding on the
      folding and stability of recombinant human endostatin were studied. The results
      show that Zn(II)-binding largely stabilizes the structure of endostatin at
      physiological pH. Under some proteolytic conditions, Zn(II)-binding also
      contributes to the integrity of the N-terminus of endostatin, which is critical
      for endostatin to maintain a stable structure. Moreover, engineering an extra
      Zn(II)-binding peptide to the N-terminus of human endostatin makes this molecule
      more stable and cooperative in the presence of Zn(II).

PMID- 17544409
TI  - Ethanol-induced death in yeast exhibits features of apoptosis mediated by
      mitochondrial fission pathway.
AB  - Cell death in yeast (Saccharomyces cerevisiae) involves several apoptotic
      processes. Here, we report the first evidence of the following processes, which
      are also characteristic of apoptosis, in ethanol-induced cell death in yeast:
      chromatin condensation and fragmentation, DNA cleavage, and a requirement for de
      novo protein synthesis. Mitochondrial fission protein, Fis1, appears to mediate
      ethanol-induced apoptosis and ethanol-induced mitochondrial fragmentation.
      However, mitochondrial fragmentation in response to elevated ethanol levels was
      not correlated with cell death. Further, in the presence of ethanol, generation
      of reactive oxygen species was elevated in mutant fis1Delta cells. Our
      characterization of ethanol-induced cell death in yeast as being Fis1-mediated
      apoptosis is likely to pave the way to overcoming limitations in large-scale
      fermentation processes, such as those employed in the production of alcoholic
      beverages and ethanol-based biofuels.

PMID- 17544410
TI  - Sequence requirements for splicing by the Cne PRP8 intein.
AB  - The dependence of protein splicing on conserved residues of the Cne PRP8 intein
      was assessed by alanine scanning mutagenesis in a foreign protein context.
      Corroboration was obtained for the involvement of residues at the splice
      junctions and of the conserved threonine and histidine of motif B. Five
      additional residues were identified as absolutely required for splicing. Variant
      W151A displayed premature C-terminal cleavage, not seen with other Cne PRP8
      mutants. We propose a model whereby W151 acts to prevent premature C-terminal
      cleavage, favoring complete splicing as opposed to two disjointed cleavage
      events.

PMID- 17544411
TI  - Cannabidiolic-acid synthase, the chemotype-determining enzyme in the fiber-type
      Cannabis sativa.
AB  - Cannabidiolic-acid (CBDA) synthase is the enzyme that catalyzes oxidative
      cyclization of cannabigerolic-acid into CBDA, the dominant cannabinoid
      constituent of the fiber-type Cannabis sativa. We cloned a novel cDNA encoding
      CBDA synthase by reverse transcription and polymerase chain reactions with
      degenerate and gene-specific primers. Biochemical characterization of the
      recombinant enzyme demonstrated that CBDA synthase is a covalently flavinylated
      oxidase. The structural and functional properties of CBDA synthase are quite
      similar to those of tetrahydrocannabinolic-acid (THCA) synthase, which is
      responsible for the biosynthesis of THCA, the major cannabinoid in drug-type
      Cannabis plants.

PMID- 17544412
TI  - Amino acid residues responsible for the recognition of dichloroacetate by
      pyruvate dehydrogenase kinase 2.
AB  - Dichloroacetate (DCA) is a promising anticancer and antidiabetic compound
      targeting the mitochondrial pyruvate dehydrogenase kinase (PDHK). This study was
      undertaken in order to map the DCA-binding site of PDHK2. Here, we present
      evidence that R114, S83, I157 and, to some extent, H115 are essential for DCA
      binding. We also show that Y80 and D117 are required for the communication
      between the DCA-binding site and active site of PDHK2. These observations provide
      important insights into the mechanism of DCA action that may be useful for the
      design of new, more potent therapeutic compounds.

PMID- 17544413
TI  - Wnt signaling enhances the activation and survival of human hepatic stellate
      cells.
AB  - Wnt signaling was implicated in pulmonary and renal fibrosis. Since Wnt activity
      is enhanced in liver cirrhosis, Wnt signaling may also participate in hepatic
      fibrogenesis. Thus, we determined if Wnt signaling modulates hepatic stellate
      cell (HSC) activation and survival. Wnt3A treatment significantly activated human
      HSCs, while this was inhibited in secreted frizzled-related protein 1 (sFRP1)
      overexpressing cells. Wnt3A treatment significantly suppressed TRAIL-induced
      apoptosis in control HSCs versus sFRP1 over-expressing cells. Particularly,
      caspase 3 was more activated in sFRP1 over-expressing cells following TRAIL and
      Wnt3A treatment. These observations imply that Wnt signaling promotes hepatic
      fibrosis by enhancing HSC activation and survival.

PMID- 17544414
TI  - Prion infection correlates with hypersensitivity of P2X7 nucleotide receptor in a
      mouse microglial cell line.
AB  - We recently established mouse microglial cells persistently infected with mouse
      adapted scrapie ME7 (ScMG20/ME7) for in vitro study of prion pathogenesis. Here,
      we found that ScMG20/ME7 cells were hypersensitive to P2X7 receptor agonists, as
      demonstrated by sustained Ca(2+) influx, membrane pore formation, cell death, and
      interleukin-1beta release. P2X7 mRNA expression was upregulated in these cells,
      and also in scrapie-infected mice brains. Treatment with pentosan polysulfate
      eliminated the infectivity and disease-related forms of prion protein from
      ScMG20/ME7 cell cultures, however, hypersensitivity of P2X7 receptors remained.
      These results suggest that prion infections may strongly affect the P2X7 receptor
      system in mouse microglial cells.

PMID- 17544415
TI  - Needs assessment for those donating to stem cell research.
AB  - OBJECTIVE: To assess information needs and decision making among couples donating
      embryos for stem cell research from outside programs. DESIGN: Qualitative and
      quantitative interview report. SETTING: Academic medical center. PATIENT(S):
      Forty-five couples donating embryos to stem cell research. MAIN OUTCOME
      MEASURE(S): Likert scales were used to assess whether participants regarded
      embryos as children and whether donation was analogous to organ or blood
      donation. Use of counseling, consideration of disposition options, and value of
      the interview were assessed. Recorded responses were analyzed for themes.
      RESULT(S): The average length of cryopreservation was 4.8 years. Twenty percent
      of the embryos were created with donor gametes; 53% of respondents viewed embryos
      as completely different from children; 31% and 27% considered embryo donation
      "identical" to organ and blood donation, respectively; 47% chose stem cell
      research to help others; 96% had not sought counseling in making their decision;
      and 20% were told they could not donate embryos to other couples. CONCLUSION(S):
      Although many couples had questions/concerns regarding disposition, few sought
      formal counseling. Outside programs may unnecessarily limit the option of
      donation to other couples. Guidelines are needed to ensure that couples making
      embryo disposition decisions are properly informed of all options, that third
      party gamete issues are addressed, and that psychological support is offered.

PMID- 17544416
TI  - Menstruation during and after caloric restriction: the 1944-1945 Dutch famine.
AB  - OBJECTIVE: To investigate the relation between exposure to the 1944-45 Dutch
      famine and concurrent and subsequent menstrual disturbances. DESIGN: Cohort
      study. SETTING: Doorlopend Onderzoek Mammacarcinoom breast cancer screening
      project, Utrecht, the Netherlands. PATIENT(S): Between 1983 and 1986,
      approximately 12,500 women (born 1911-41) reported their individual famine
      experiences. MAIN OUTCOME MEASURE(S): Irregular menstruation during the famine;
      time to regular menses after menarche, and menstrual patterns in adulthood after
      childhood famine. RESULT(S): The famine had a direct impact on menstruation. The
      odds ratio (OR) of concurrent irregular menses in severely versus unexposed women
      was 8.85 (95% confidence interval [CI], 7.31-10.70). Women exposed to severe
      famine before menarche were 1.51 (95% CI, 1.15-1.98) times more likely to
      experience irregular menses for a prolonged time after menarche compared with the
      unexposed. This association was stronger in women with an early menarche. When
      the menstrual pattern was assessed in adulthood by menstrual diaries, a
      nonsignificant tendency of increased irregularity (OR, 1.13; 95% CI, 0.82-1.54)
      and regular but long menstrual cycles (OR, 1.41; 95% CI, 0.89-2.23) was observed
      in women exposed to severe famine. CONCLUSION(S): Famine relates to concurrent
      menstrual irregularity, and exposure in childhood seems to affect the subsequent
      menstrual pattern.

PMID- 17544417
TI  - Does histopathologic tumor type or vascular invasion influence spermatogenesis in
      testicular cancer?
AB  - OBJECTIVE: To assess the quality and activity of spermatogenesis in the
      contralateral healthy testicle at the time of orchiectomy and to assess whether
      any tumor-related factor such as tumor type or vascular invasion is a risk factor
      for impaired spermatogenesis. DESIGN: Retrospective cohort study. SETTING:
      University hospital. PATIENT(S): Seventy-six patients undergoing orchiectomy for
      seminoma or nonseminomatous germ cell tumor (NSGCT). INTERVENTION(S): Open biopsy
      of contralateral healthy testicle at the time of orchiectomy. MAIN OUTCOME
      MEASURE(S): Quality of spermatogenesis using median and highest Johnsen score in
      correlation with histopathologic tumor type, vascular invasion, and serum tumor
      markers and hormone levels. RESULT(S): Contralateral spermatogenesis is reduced
      in seminomas and in NSGCTs, with median Johnsen scores of 8.9 and 8.6,
      respectively. Similar results were seen in tumors with vascular invasion (median
      Johnsen score 8.8 [range 8.2-9.5]) and without vascular invasion (median Johnsen
      score 8.8 [range 8.1-9.2]). Areas with good-quality spermatogenesis were found in
      88.9% of seminoma and 92.5% of NSGCT biopsies. CONCLUSION(S): Testicular cancer
      is associated with impaired spermatogenesis, but neither the histopathologic
      tumor type nor the presence of vascular invasion correlated with significantly
      reduced spermatogenesis.

PMID- 17544418
TI  - Markov modeling of vasectomy reversal and ART for infertility: how do obstructive
      interval and female partner age influence cost effectiveness?
AB  - OBJECTIVE: To apply Markov models to assess the cost effectiveness of the
      relative impact of obstructive interval and female partner age on fertility using
      either assisted reproductive technology (ART) or vasectomy reversal, and
      elucidate the impact of these variables on fertility. DESIGN: Markov models based
      on review of published literature and available ART outcome data. SETTING:
      University-based clinical practice. PATIENT(S): Simulation runs of 50,000
      patients for each analysis. INTERVENTION(S): Varying vasectomy obstructive
      interval and maternal age. MAIN OUTCOME MEASURE(S): Cost effectiveness,
      willingness to pay (WTP), and net health benefit. RESULT(S): Base case analysis
      showed ART yields a higher pregnancy rate and higher cost than vasectomy
      reversal. Sensitivity analysis showed female age has a greater effect on cost
      effectiveness than obstructive interval. At a WTP < $65,000, vasectomy reversal
      is more cost effective than ART. With increasing WTP, ART is more cost effective
      over wider windows of female age. CONCLUSION(S): Markov modeling of fertility
      after vasectomy suggests female age has more impact than vasectomy obstructive
      interval on cost effectiveness.

PMID- 17544419
TI  - Alterations in sperm motility after acute oral administration of sildenafil or
      tadalafil in young, infertile men.
AB  - OBJECTIVE: To evaluate the acute effect of sildenafil and tadalafil on seminal
      parameters in young, infertile patients. DESIGN: Prospective, randomized, double
      blind, crossover clinical investigation on semen parameters after the
      administration of a single dose of sildenafil (50 mg) or tadalafil (20 mg).
      SETTING: An academic hospital as well as a male infertility center and clinical
      andrology laboratories. PATIENT(S): Eighteen young, infertile men.
      INTERVENTION(S): Oral administration of a single dose of sildenafil (50 mg) or
      tadalafil (20 mg) in a blind, randomized order. The semen samples were collected
      1 or 2 hours after each treatment. MAIN OUTCOME MEASURE(S): Changes in sperm
      parameters after sildenafil and tadalafil administration, compared with the basal
      conditions. RESULT(S): A significant increase in sperm progressive motility
      (median value, 37.0% vs. 28.5%) was observed after sildenafil administration as
      compared with baseline; in contrast, a significant decreased value was observed
      after tadalafil (median value, 21.5% vs. 28.5%). CONCLUSION(S): These preliminary
      results indicate that sperm motility appears to be acutely affected in young,
      infertile patients by a single dose of sildenafil and tadalafil, with opposite
      effects: stimulatory by the former and inhibitory by the latter.

PMID- 17544420
TI  - Extremely elevated serum CA-125 level as a result of unruptured unilateral
      endometrioma: the highest value reported.
AB  - OBJECTIVE: To present a case of a unilateral endometrioma with extremely elevated
      serum CA-125 levels. DESIGN: Case report. SETTING: University hospital.
      PATIENT(S): A 25-year-old woman with left adnexal mass and extremely elevated
      serum CA-125 level, 7,900 U/mL, underwent laparoscopy. There were unilateral
      endometrioma and stage IV endometriosis. INTERVENTION(S): Laparoscopic excision
      of the endometrioma, unilateral salpingectomy, adhesiolysis, ablation of
      endometriotic foci, and partial omentectomy were performed, and histopathologic
      results confirmed the diagnosis of endometriosis. MAIN OUTCOME MEASURE(S):
      Extremely elevated serum CA-125 levels and unruptured ovarian endometrioma.
      RESULT(S): On the second, sixth, and 13th days of the menstrual period, serum CA
      125 levels were 7,900 U/mL, 1,577 U/mL, and 627 U/mL, respectively. On the third
      postoperative day serum CA-125 level was 56 U/mL. CONCLUSION(S): Ovarian
      endometrioma and advanced endometriosis may be associated with extremely elevated
      serum CA-125 levels. For this reason ovarian endometrioma should be considered
      with respect to differential diagnosis of reproductive-age women presenting with
      an ovarian mass even if it resembles an ovarian malignancy.

PMID- 17544421
TI  - Efficacy of vaginal danazol treatment in women with recurrent deeply infiltrating
      endometriosis.
AB  - OBJECTIVE: To describe a safe long-term medical treatment for deeply infiltrating
      endometriosis, a critical condition characterized by multiple painful symptoms
      and a high recurrence rate after surgical treatment. DESIGN: Prospective study.
      SETTING: University of Siena. PATIENT(S): Twenty-one women with deeply
      infiltrating endometriosis. INTERVENTION(S): In a nonrandomized prospective study
      a low dose of vaginal danazol (200 mg/d) was self-administered for 12 months.
      After a previous laparoscopic surgery, these patients had reported recurrent
      severe dyspareunia, dysmenorrhea, and pelvic pain (in five cases also painful
      defecation). MAIN OUTCOME MEASURE(S): Before and every 3 months during the
      treatment a visual analogue pain scale was used. Transvaginal and transrectal
      ultrasound examinations were performed before and after 6 and 12 months of
      treatment. Adverse effects were registered, and serum concentration of
      cholesterol, triglycerides, aspartate aminotransferase, alanine aminotransferase,
      glycemia, protein S, protein C, antithrombin III, and homocysteine was evaluated
      before and after 12 months. RESULT(S): Dysmenorrhea, dyspareunia, and pelvic pain
      significantly decreased within 3 months and disappeared after 6 months of
      treatment, with a persistent effect during the 12 months of treatment. A relief
      of painful defecation was also shown. Ultrasound examination showed a reduction
      of the nodularity in the rectovaginal septum within 6 months. The medical
      treatment did not affect metabolic or thrombophilic parameters; few local vaginal
      adverse effects were reported. CONCLUSION(S): Vaginal danazol resulted in
      effective medical treatment for the various painful symptoms in women with
      recurrent deeply infiltrating endometriosis, and because of the lack of
      significant adverse effects it may be proposed as an alternative to repeated
      surgery.

PMID- 17544422
TI  - Complex endometrial wave-patterns in IVF.
AB  - OBJECTIVE: To reanalyze ultrasound images from IVF cycles with the aim of
      developing a refined endometrial wave classification system, which will allow
      description as well of the more complex endometrial wave patterns. DESIGN:
      Descriptive study. SETTING: University hospital-based fertility clinic.
      PATIENT(S): Twenty-four patients undergoing IVF. INTERVENTION(S): Ultrasound
      examination was performed on the day of hCG administration. MAIN OUTCOME
      MEASURE(S): Endometrial wave type and intraobserver and interobserver agreement.
      RESULT(S): Two new wave types were added to the endometrial wave types that were
      described in the existing wave classification system: recoiling CF waves and a
      standing wave. Furthermore, an alternation between CF waves and FC waves in the
      same fragment was described. Calculation of interobserver and intraobserver
      agreement resulted in a kappa value reflecting strong agreement. CONCLUSION(S):
      The refined endometrial wave classification system makes it possible to describe
      the more complex wave types that can be detected in IVF cycles on the day of hCG
      administration.

PMID- 17544423
TI  - Effect of choline-supplemented sodium-depleted slow freezing versus vitrification
      on mouse oocyte meiotic spindles and chromosome abnormalities.
AB  - OBJECTIVE: To evaluate and compare vitrification and choline-supplemented sodium
      depleted slow freezing of mouse oocytes. DESIGN: Animal study. SETTING:
      University-affiliated hospital. ANIMAL(S): CD-1 mice. INTERVENTION(S): Oocyte
      cryopreservation by vitrification or choline-supplemented sodium-depleted slow
      freezing. MAIN OUTCOME MEASURE(S): Survival rate, fertilization and embryonic
      development in vitro, meiotic spindle and chromosome configuration, and
      aneuploidy screening after parthenogenetic activation. RESULT(S): A total of 564
      oocytes were vitrified, and 791 oocytes were cryopreserved using the slow
      freezing. The survival rates were 91.8% (518/564) and 73.3% (579/791),
      respectively. After IVF, the cleavage and blastocyst formation rates of vitrified
      oocytes were significantly higher than those of slow-frozen oocytes (63.6% vs.
      39.9% and 30.50% vs. 20.2%, respectively). Vitrified oocytes were more likely
      than slow-frozen oocytes to maintain normal meiotic spindles and chromosome
      alignment (86.9% vs. 70.1%). However, the incidence of aneuploidy was similar in
      vitrified oocytes and slow-frozen oocytes (9.30% vs. 8.7%). CONCLUSION(S):
      Vitrification is superior to choline-supplemented sodium-depleted slow freezing,
      leading to improved survival, fertilization, and embryonic development in vitro.
      Analysis of meiotic spindle integrity and chromosome alignment indicates that
      less damage was detected in vitrified oocytes. However, the incidence of
      aneuploidy is similar in both vitrified and slow-frozen oocytes.

PMID- 17544424
TI  - Effects of larval exposure to estradiol on spermatogenesis and in vitro gonadal
      steroid secretion in African clawed frogs, Xenopus laevis.
AB  - Estrogen or eco-estrogenic chemicals can disrupt normal gonadal sex
      differentiation, causing intersex formation and feminization in amphibians. The
      cellular basis for estrogen-induced sex reversal is not well understood. In the
      present study, we investigated the concentration- and stage-dependent effects of
      estradiol (E(2)) exposure during the larval period on histological
      characteristics of gonadal sex differentiation and gonadal sex steroid secretion
      in vitro in the African clawed frog, Xenopus laevis. Embryos were exposed to E(2)
      (1, 10, or 100 microg/L) or vehicle control through metamorphosis and then
      allowed to develop in untreated medium for 2-mo post-metamorphosis. To
      investigate gonadal sex differentiation and development during and after
      exposure, gonadal samples were collected at different developmental stages.
      Gonadal sex differentiation did not occur before NF stage 52 in any group. At NF
      stage 54-55 primordial germ cells (PGCs) were observed in both cortical and
      medullary regions of developing tadpoles gonads in the control, 1 and 10 microg/L
      E(2) treatments, but were observed only in the cortical region of tadpoles
      exposed to 100 microg/L E(2). E(2) increased the percent of spermatocytes,
      spermatids, and spermatozoa compared to controls. Larval E(2) exposure did not
      alter hCG-induced gonadal testosterone secretion in vitro but significantly
      increased E(2) secretion from ovaries of juvenile frogs. Our results indicate
      that E(2) exposure during larval development appears to prevent PGC migration to
      the medulla of developing gonads in a concentration-dependent manner. The degree
      of PGC migration to the medulla may be related to the degree of E(2)-induced
      intersex formation and feminization in X. laevis. E(2) exposure during the larval
      period accelerates spermatogenesis and can increase ovarian E(2) secretion in
      juvenile frogs.

PMID- 17544425
TI  - Application of Gaussian processes for black-box modelling of biosystems.
AB  - Different models can be used for nonlinear dynamic system identification and the
      Gaussian process model is a relatively new option with several interesting
      features: model predictions contain the measure of confidence, the model has a
      small number of training parameters and facilitated structure determination, and
      different possibilities of including prior knowledge exist. In this paper the
      framework for the identification of a dynamic system model based on Gaussian
      processes is shown, illustrated on a simulated bioreactor example and then
      applied to two case studies. The first one addresses modelling of the
      nitrification process in a wastewater treatment plant and the second models
      biomass growth in the Lagoon of Venice. Special emphasis is placed on model
      validation, an often underemphasised part of the identification procedure, where
      the Gaussian model prediction variance can be utilised.

PMID- 17544426
TI  - A novel robust speed controller scheme for PMBLDC motor.
AB  - The design of speed and position controllers for permanent magnet brushless DC
      motor (PMBLDC) drive remains as an open problem in the field of motor drives. A
      precise speed control of PMBLDC motor is complex due to nonlinear coupling
      between winding currents and rotor speed. In addition, the nonlinearity present
      in the developed torque due to magnetic saturation of the rotor further
      complicates this issue. This paper presents a novel control scheme to the
      conventional PMBLDC motor drive, which aims at improving the robustness by
      complete decoupling of the design besides minimizing the mutual influence among
      the speed and current control loops. The interesting feature of this robust
      control scheme is its suitability for both static and dynamic aspects. The
      effectiveness of the proposed robust speed control scheme is verified through
      simulations.

PMID- 17544427
TI  - Screw augmentation in displaced femoral neck fractures. Clinical and histological
      results using a new composite.
AB  - We wanted to assess a new technique for augmentation of parallel screws in
      internal fixation of displaced femoral neck fractures with a bis-GMA-based
      composite delivered around the screw head. Twenty-one consecutive patients
      admitted with displaced femoral neck fractures were operated with internal
      fixation with two parallel Olmed screws augmented with the composite, and
      followed for 24 months. The composite was introduced through the lumen of the
      cannulated screws and deposited in the femoral head around the threaded part of
      the screws. The procedure of augmenting was technically feasible and operation
      time was on average 33 min. Eleven patients were re-operated due to healing
      complications within 24 months. There were five redisplacements, four non-unions
      and two cases of avascular necrosis. Histological examination of four extracted
      femoral heads showed fragmentation of the composite into small particles with
      foreign-body response with giant cells and macrophages along with granulation
      tissue formation and low grade inflammation. The method of augmentation was
      technically easy, but the failure rate was high and the fragmentation of the
      composite with inflammatory response found on histology is noteworthy.

PMID- 17544428
TI  - Selective non-operative management of solid organ injury following abdominal
      gunshot wounds.
AB  - BACKGROUND: The objective of this study was to evaluate the outcome of patients
      sustaining a torso gunshot wound with documented solid organ injury. Our
      hypothesis was that the non-operative management of isolated solid organ injuries
      is a safe management option for a select group of patients. METHODS: A
      retrospective review of a prospectively collected database was conducted to
      identify all patients sustaining a torso gunshot resulting in a solid organ
      injury undergoing non-operative management over a 5-year period (12/1999
      01/2005). Patient demographics, injury details, diagnostic imaging, outcome and
      follow-up were reviewed. RESULTS: Of 644 gunshot wounds to the torso, 144 (22%)
      underwent non-operative management. Thirteen of these patients (9%) had 16 solid
      organ injuries (10 liver, 4 kidney and 2 spleen). CT characterisation of the
      isolated solid organ injury ranged from AAST Grade I-IV. One of 13 patients
      failed non-operative management and subsequently underwent laparotomy, which was
      non-therapeutic. Clinical follow-up was available in all patients for an average
      of 101 days (median 27, range 6-473). The organ salvage rate was 100%. SUMMARY:
      In select haemodynamically stable patients without peritonitis able to undergo
      serial clinical examination, solid organ injury is not a contra-indication to non
      operative management. In the appropriate setting, non-operative management of
      solid organ injury after gunshot wounding is associated with a high rate of
      success and organ salvage.

PMID- 17544429
TI  - Instructions limiting the number of steps do not affect the kinetics of the
      threshold of balance recovery in younger adults.
AB  - To our knowledge, no one has explored the effect of modifications in balance
      recovery instructions on the kinetics of the threshold of balance recovery. In
      particular, the effect of instructions limiting the number of steps on joint
      torques at the maximum lean angle has not been quantified. We determined the
      joint torques at the ankle, knee and hip of 28 younger adults recovering balance
      at their maximum lean angle using: (i) only a single step, (ii) no more than two
      steps and (iii) no limit on the number of steps. Results showed that instructions
      limiting the number of steps did not affect peak normalized joint torques by more
      than 0.0083 or 10Nm except for knee and hip flexion torques from first to second
      heel strike for the first step leg as well as from second toe-off to heel strike
      for the second step leg. However, these large differences in peak normalized
      joint torques after the first step were simply caused by the additional steps
      used when participants could take more than one step compared to when
      participants were limited to only a single step. Between the three limits on the
      number of steps, the kinetics of both legs were nearly identical up to the end of
      the first step and the additional steps did not help to increase the maximum lean
      angle. Therefore, we have demonstrated that instructions limiting or not limiting
      the number of steps appear to be equally valid to study falls in younger adults.

PMID- 17544430
TI  - In vivo behavior of muscle fascicles and tendinous tissues in human tibialis
      anterior muscle during twitch contraction.
AB  - In this study we investigated the time course of length and velocity of muscle
      fascicles and tendinous tissues (TT) during isometric twitch contraction, and
      examined how their interaction relates to the time course of external torque and
      muscle fascicle force generation. From seven males, supra-maximal twitch
      contractions (singlet) of the tibialis anterior muscle were induced at 30 degrees
      , 10 degrees and -10 degrees plantar flexed positions. The length and velocity of
      fascicles and TT were determined from a series of their transverse ultrasound
      images. The maximal external torque appeared when the shortening velocity of
      fascicles was zero. The fascicle and TT length, and external torque showed a 10
      30 ms delay of each onset, with a significant difference in half relaxation times
      at -10 degrees . The time course of TT elongation, and fascicle and tendinous
      velocities did not differ between joint angles. Curvilinear length-force
      properties, whose slope of quasi-linear part was ranged from -15.0 to -5.9 N/mm
      for fascicles and 5.4 to 14.3N/mm for TT, and a loop-like pattern of velocity
      force properties, in which the mean power was ranged from 0.14 to 0.80 W for
      fascicles, and 0.14 to 0.81 W for TT were also observed. These results were
      attributed to the muscle-tendon interaction, depending on the slack and non
      linearity of length-force relationship of compliant TT. We conclude that the
      mechanical interaction between fascicles and TT, are significant determinants of
      twitch force and time characteristics.

PMID- 17544431
TI  - Force-induced activation of talin and its possible role in focal adhesion
      mechanotransduction.
AB  - It is now well established that cells can sense mechanical force, but the
      mechanisms by which force is transduced into a biochemical signal remain poorly
      understood. One example is the recruitment of vinculin to reinforce initial
      contacts between a cell and the extracellular matrix (ECM) due to tensile force.
      Talin, an essential linking protein in an initial contact, contains at least one
      vinculin-binding site (VBS) that is cryptic and inactive in the native state. The
      N-terminal five-helix bundle of talin rod is a stable structure with a known
      cryptic VBS1. The perturbation of this stable structure through elevated
      temperature or destabilizing mutation activates vinculin binding. Although the
      disruption of this subdomain by transmitted mechanical force is a potential cue
      for the force-induced focal adhesion strengthening, the molecular basis for this
      mechanism remains elusive. Here, molecular dynamics (MD) is employed to
      demonstrate a force-induced conformational change that exposes the cryptic
      vinculin-binding residues of VBS1 to solvent under applied force along a
      realistic pulling direction. VBS1 undergoes a rotation of 62.0 +/- 9.5 degrees
      relative to its native state as its vinculin-binding residues are released from
      the tight hydrophobic core. Charged and polar residues on the VBS1 surface are
      the site of force transmission that strongly interact with an adjacent alpha
      helix, and in effect, apply torque to the VBS1 to cause its rotation. Activation
      was observed with mean force of 13.2 +/-8.0 pN during constant velocity
      simulation and with steady force greater than 18.0 pN.

PMID- 17544432
TI  - "Fast peaks" in chromatograms of Sudan dyes.
AB  - The analysis of Sudan dyes has gained considerable attention during last years.
      In several publications multiple peaks in chromatograms of Sudan III and Sudan IV
      have been detected. It is demonstrated in this work that if the sample is kept in
      darkness before analysis, only one chromatographic peak appears for Sudan III or
      Sudan IV. In normal lighting conditions two peaks are observed. This light
      induced effect can lead to under- or overestimation of the Sudan III and Sudan IV
      content by 10% and false-positive detection of Sudan I and Sudan II, if proper
      care is not taken. Appearance of the second peak in chromatograms of Sudan III
      and Sudan IV is attributed to photochromic E-Z isomerization of these dyes.

PMID- 17544433
TI  - Application of mass spectrometer-inverse gas chromatography to study polymer
      solvent diffusivity and solubility.
AB  - The application of a mass spectrometer detector in capillary column inverse gas
      chromatography is shown to be a valuable tool in the measurement of diffusion and
      solubility in polymer-solvent systems. The component specific detector provides
      excellent results for binary polymer-solvent systems, but it is particularly
      valuable because it can be readily applied to multicomponent systems. Results for
      a number of infinitely dilute solvents in poly(vinyl acetate) (PVAc) are reported
      over a range of temperature from 60 to 150 degrees C. Results are also reported
      for finite concentrations of toluene and methanol in PVAc from 60 to 110 degrees
      C. Finally, the technique was applied to study the effect of finite
      concentrations of toluene on the diffusion coefficients of THF and cyclohexane in
      PVAc. The experimental data compare well with literature values for both infinite
      and finite concentrations, indicating that the experimental protocol described in
      this work is sound.

PMID- 17544434
TI  - Chemical fingerprinting of petroleum biomarkers in biota samples using retention
      time locking chromatography and multivariate analysis.
AB  - This work was conducted to study a new separation and evaluation approach for the
      chemical fingerprinting of petroleum biomarkers in biota samples. The final aim
      of this work was to study the correlation between the observed effects in the
      shore habitats (mussels and limpets) and one pollution source: the oil spill of
      the Prestige tanker. The method combined a clean-up step of the biota extracts
      (mussels and limpets), the retention-time locking of the gas chromatographic set
      up, and the multivariate data analysis of the chromatograms. For clean-up, solid
      phase extraction and gel permeation chromatography were compared, and 5g Florisil
      cartridges assured the lack of interfering compounds in the last extracts. In
      order to assure reproducible retention times and to avoid the realignment of the
      chromatograms, the retention-time locking feature of our gas chromatography-mass
      spectrometry (GC-MS) set up was used. Finally, in the case of multivariate
      analysis, the GC-MS chromatograms were treated, essentially by derivatization and
      by normalization, and all the chromatograms at m/z 191 (terpenes), m/z 217-218
      (steranes and diasteranes) and m/z 231 (triaromatic steranes) were treated by
      means of principal component analysis. Furthermore, slightly different four oil
      samples from the Prestige oil spill were analyzed following the Nordtest method,
      and the GC-MS chromatograms were considered as the reference chemical
      fingerprints of the sources. In this sense, the correlation between the studied
      samples, including sediments and biota samples, and the source candidate was
      completed by means of a supervised pattern recognition method. As a result, the
      method proposed in this work was useful to identify the Prestige oil spill as the
      source of many of the analyzed samples.

PMID- 17544435
TI  - Modeling the sorption kinetics of divalent metal ions onto mineral adsorbent
      using integral method.
AB  - A mathematical model has been developed that could predict kinetic parameters for
      the adsorption of divalent cations (lead, copper and zinc) onto low-grade rock
      phosphate using experimental data. The experiments were conducted with the
      initial concentrations of metal ions ranging from 10 to 100 mg/L. The
      mathematical model is based on application of Freundlich isotherm to mass
      transfer across the film surrounding the adsorbent. A code in C programming is
      used to numerically integrate the model equation, and to obtain the best
      simulated values of Freundlich constants K, N, order of reaction n, and film
      transfer coefficient, alpha. It is observed that the adsorption of metal ions on
      rock phosphate is more sensitive to N,n, and alpha in comparison to K, and lead
      is adsorbed more favorably than copper and zinc.

PMID- 17544436
TI  - Alpha-synuclein accumulates in the brain of scrapie-affected sheep and goats.
AB  - Immunohistochemical examination demonstrated widespread granular deposits of
      alpha-synuclein (alphaSN) in the brains of sheep and goats with natural scrapie,
      especially in the cornu ammonis and subiculum of the hippocampus; this contrasted
      with the diffuse and non-granular immunolabelling seen in healthy controls. There
      was non-regular "co-localization" of PrP(Sc) and alphaSN. The findings resembled
      those reported in Creutzfeldt-Jakob disease and in experimental prion disease in
      hamsters and mice. The results suggest that perturbation of alphaSN metabolism
      plays a role in human and animal prion diseases.

PMID- 17544437
TI  - Effect of the addition of four potential probiotic strains on the survival of
      pacific white shrimp (Litopenaeus vannamei) following immersion challenge with
      Vibrio parahaemolyticus.
AB  - Four bacterial strains isolated from the gastrointestinal tract of adult shrimp
      Litopenaeus vannamei, Vibrio alginolyticus UTM 102, Bacillus subtilis UTM 126,
      Roseobacter gallaeciensis SLV03, and Pseudomonas aestumarina SLV22, were
      evaluated for potential use as probiotics for shrimp. In vitro studies
      demonstrated antagonism against the shrimp-pathogenic bacterium, Vibrio
      parahaemolyticus PS-017. Feeding shrimp with diets containing the potential
      probiotics showed the best feed conversion ratio in comparison with the control
      groups. After feeding with the potential probiotics for 28 days, challenge by
      immersion indicated effectiveness at reducing disease caused by V.
      parahaemolyticus in shrimp.

PMID- 17544438
TI  - Solenopsis invicta virus-1 tissue tropism and intra-colony infection rate in the
      red imported fire ant: a quantitative PCR-based study.
AB  - Quantitative real-time PCR was employed to measure the Solenopsis invicta virus 1
      (SINV-1) load in tissues, individuals, and among colonies of the red imported
      fire ant, S. invicta Buren. Among tissues examined from SINV-1-infected adults
      and larvae, the alimentary canal (specifically the midgut) consistently had the
      highest number of SINV-1 genome copies (91.1 and 99.9%, respectively). Negative
      staining of a supernatant of the gut homogenate demonstrated the presence of
      spherical virus particles with a diameter of 30-35 nm, consistent with SINV-1.
      The number of SINV-1 genome copies in infected larvae and workers from the same
      queenright colonies were similar to each other. In other words, the infection
      rate was consistent among both developmental stages. No significant differences
      were observed in SINV-1 genome copy number among infected colonies sampled during
      the winter and summer. Although the SINV-1 infection rate of summer-collected
      mounds was previously shown to be six-times higher than winter-collected mounds,
      the intra-colony infection rate appears to be unaffected by season. Perhaps less
      inter-mound interaction during the winter months among S. invicta restricts
      spread of the virus. A positive correlation between intra-colony infection rate
      and mean SINV-1 genome copy number per ant was also observed. Based on these
      results, it is likely that SINV-1 replicates in gut epithelia of S. invicta and
      virus is shed into the gut lumen where it may be transmitted to nestmates by
      trophallaxis.

PMID- 17544439
TI  - Positron molecular imaging, an in vivo glimpse of the genome.

PMID- 17544440
TI  - Active-site properties of the oxidized and reduced C-terminal domain of DsbD
      obtained by NMR spectroscopy.
AB  - The periplasmic C-terminal domain of the Escherichia coli DsbD protein (cDsbD)
      has a thioredoxin fold. The two cysteine residues in the CXXC motif serve as the
      reductant for the disulfide bond of the N-terminal domain which can in turn act
      as a reductant for various periplasmic partners. The resulting disulfide bond in
      cDsbD is reduced via an unknown mechanism by the transmembrane helical domain of
      the protein. We show by NMR analysis of (13)C, (15)N-labelled cDsbD that the
      protein is rigid, is stable to extremes of pH and undergoes only localized
      conformational changes in the vicinity of the CXXC motif, and in adjacent regions
      of secondary structure, upon undergoing the reduced/oxidized transition. pK(a)
      values have been determined, using 2D NMR, for the N-terminal cysteine of the
      CXXC motif, Cys461, as well as for other active-site residues. It is demonstrated
      using site-directed mutagenesis that the negative charges of the side-chains of
      Asp455 and Glu468 in the active site contribute to the unusually high pK(a)
      value, 10.5, of Cys461. This value is higher than expected from knowledge of the
      reduction potential of cDsbD. In a double mutant of cDsbD, D455N/E468Q, the pK(a)
      value of Cys461 is lowered to 8.6, a value close to that expected for an
      unperturbed cysteine residue. The pK(a) value of the second cysteine in wild-type
      cDsbD, Cys464, is significantly higher than the maximum pH value that was studied
      (pH 12.2).

PMID- 17544441
TI  - Carboxyl terminus of Nkx2.5 impairs its interaction with p300.
AB  - The transcription factor Nkx2.5 plays critical roles in controlling cardiac
      specific gene expression. Previous reports demonstrated that Nkx2.5 is only a
      modest transactivator due to the auto-inhibitory effect of its C-terminal domain.
      Deletion of the C-terminal domain, mimicking conformational change, evokes
      vigorous transactivation activity. Here, we show that a C-terminal defective
      mutant of Nkx2.5 improves the occupation of p300 at the ANF promoter compared
      with full-length Nkx2.5, leading to hyperacetylation of histone H4. We reveal
      that p300 is a cofactor of Nkx2.5, markedly potentiating Nkx2.5-dependent
      transactivation, whereas E1A antigen impairs Nkx2.5 activity. Furthermore, p300
      can acetylate Nkx2.5 and display an acetyltransferase-independent mechanism to
      coactivate Nkx2.5. Physical interaction between the N-terminal activation domain
      of Nkx2.5 and the C/H3 domain of p300 are identified by GST pull-down assay.
      Point mutants of the N-terminal modify the transcriptional activity of Nkx2.5 and
      interaction with p300. Deletion of the C-terminal domain greatly facilitates p300
      binding and improves the susceptibility of Nkx2.5 to histone deacetylase
      inhibitor. These results establish that p300 acts as an Nkx2.5 cofactor and
      facilitates increased Nkx2.5 activity by relieving the conformational impediment
      of its inhibitory C-terminal domain.

PMID- 17544442
TI  - Domain topology of the p62 complex within the 3-D architecture of the nuclear
      pore complex.
AB  - The nuclear pore complex (NPC) is the only known gateway for exchange of
      macromolecules between the cytoplasm and nucleus of eukaryotic cells. One key
      compound of the NPC is the p62 subcomplex, which consists of the nucleoporins
      p62, p54, and p58/p45 and is supposed to be involved in nuclear protein import
      and export. Here we show the localization of distinct domains of the p62 complex
      by immuno-electron microscopy using isolated nuclei from Xenopus oocytes. To
      determine the exact position of the p62 complex, we examined the localization of
      the C and N-terminal domains of p62 by immunogold-labeling using domain-specific
      antibodies against p62. In addition we expressed epitope-tagged versions of p62,
      p54, and p58 in Xenopus oocytes and localized the domains with antibodies against
      the tags. This first systematic analysis of the domain topology of the p62
      complex within the NPC revealed that the p62 complex is anchored to the
      cytoplasmic face of the NPC most likely by the coiled-coil domains of the three
      nucleoporins. Furthermore, we found the phenylalanine-glycine (FG)-repeat domain
      of p62, but not of p58 and p54, to be of mobile and flexible nature.

PMID- 17544443
TI  - The crystal structure of lambda-Gam protein suggests a model for RecBCD
      inhibition.
AB  - In Escherichia coli, RecBCD processes double-stranded DNA breaks during the
      initial stages of homologous recombination. RecBCD contains helicase and nuclease
      activities, and unwinds and digests the blunt-ended DNA until a specific eight
      nucleotide sequence, Chi, is encountered. Chi modulates the nuclease activity of
      RecBCD and results in a resected DNA end, which is a substrate for RecA during
      subsequent steps in recombination. RecBCD also acts as a defence mechanism
      against bacteriophage infection by digesting linear viral DNA present during
      virus replication or resulting from the action of restriction endonucleases. To
      avoid this fate, bacteriophage lambda encodes the gene Gam whose product is an
      inhibitor of RecBCD. Gam has been shown to bind to RecBCD and inhibit its
      helicase and nuclease activities. We show that Gam inhibits RecBCD by preventing
      it from binding DNA. We have solved the crystal structure of Gam from two
      different crystal forms. Using the published crystal structure of RecBCD in
      complex with DNA we suggest models for the molecular mechanism of Gam-mediated
      inhibition of RecBCD. We also propose that Gam could be a mimetic of single
      stranded, and perhaps also double-stranded, DNA.

PMID- 17544444
TI  - Conservation and diversity among the three-dimensional folds of the
      Dicistroviridae intergenic region IRESes.
AB  - Internal ribosome entry site (IRES) RNAs are necessary for successful infection
      of many pathogenic viruses, but the details of the RNA structure-based mechanism
      used to bind and manipulate the ribosome remain poorly understood. The IRES RNAs
      from the Dicistroviridae intergenic region (IGR) are an excellent model system to
      understand the fundamental tenets of IRES function, requiring no protein factors
      to manipulate the ribosome and initiate translation. Here, we explore the
      architecture of four members of the IGR IRESes, representative of the two
      divergent classes of these IRES RNAs. Using biochemical and structural probing
      methods, we show that despite sequence variability they contain a common three
      dimensional fold. The three-dimensional architecture of the ribosome binding
      domain from these IRESes is organized around a core helical scaffold, around
      which the rest of the RNA molecule folds. However, subtle variation in the folds
      of these IRESes and the presence of an additional secondary structure element
      suggest differences in the details of their manipulation of the large ribosomal
      subunit. Overall, the results demonstrate how a conserved three-dimensional RNA
      fold governs ribosome binding and manipulation.

PMID- 17544445
TI  - A genome-wide Ras-effector interaction network.
AB  - Here using structural information and protein design tools we have drawn the
      network of interactions between 20 Ras subfamily proteins with 50 putative Ras
      binding domains. To validate this network we have cloned six poorly characterized
      Ras binding domains (RBD) and two Ras proteins (RERG, DiRas1). These, together
      with previously described RBD domains, Ras and Rap proteins have been analyzed in
      70 pull-down experiments. Comparing our interaction network with these and
      previous pull-down experiments (total of 150 cases) shows a very high accuracy
      for distinguishing between binders and non-binders ( approximately 0.80).
      Bioinformatics information was integrated to distinguish those in vitro
      interactions that are more likely to be relevant in vivo. We proposed several new
      interactions between Ras family members and effector domains that are of
      relevance in understanding the physiological role of these proteins. More broadly
      our results demonstrate that (domain-domain) interaction specificities between
      members of protein families can be accurately predicted using structural
      information.

PMID- 17544446
TI  - Assembly of the small outer capsid protein, Soc, on bacteriophage T4: a novel
      system for high density display of multiple large anthrax toxins and foreign
      proteins on phage capsid.
AB  - Bacteriophage T4 capsid is a prolate icosahedron composed of the major capsid
      protein gp23*, the vertex protein gp24*, and the portal protein gp20. Assembled
      on its surface are 810 molecules of the non-essential small outer capsid protein,
      Soc (10 kDa), and 155 molecules of the highly antigenic outer capsid protein, Hoc
      (39 kDa). In this study Soc, a "triplex" protein that stabilizes T4 capsid, is
      targeted for molecular engineering of T4 particle surface. Using a defined in
      vitro assembly system, anthrax toxins, protective antigen, lethal factor and
      their domains, fused to Soc were efficiently displayed on the capsid. Both the N
      and C termini of the 80 amino acid Soc polypeptide can be simultaneously used to
      display antigens. Proteins as large as 93 kDa can be stably anchored on the
      capsid through Soc-capsid interactions. Using both Soc and Hoc, up to 1662
      anthrax toxin molecules are assembled on the phage T4 capsid under controlled
      conditions. We infer from the binding data that a relatively high affinity capsid
      binding site is located in the middle of the rod-shaped Soc, with the N and C
      termini facing the 2- and 3-fold symmetry axes of the capsid, respectively. Soc
      subunits interact at these interfaces, gluing the adjacent capsid protein
      hexamers and generating a cage-like outer scaffold. Antigen fusion does interfere
      with the inter-subunit interactions, but these interactions are not essential for
      capsid binding and antigen display. These features make the T4-Soc platform the
      most robust phage display system reported to date. The study offers insights into
      the architectural design of bacteriophage T4 virion, one of the most stable
      viruses known, and how its capsid surface can be engineered for novel
      applications in basic molecular biology and biotechnology.

PMID- 17544447
TI  - Frontotemporal dementia in Oman: cognitive behavioural profile and neuroimaging
      characteristics; a prospective hospital-based study.
AB  - Frontotemporal dementia is increasingly recognised as an important cause of early
      onset dementia and is considered to be the second commonest neurodegenerative
      dementia after Alzheimer's disease. We describe the cognitive, behavioural
      profile and neuroimaging characteristics of 6 patients with frontal variant of
      Frontotemporal dementia that were evaluated at the cognitive behavioural clinic
      at this tertiary referral teaching hospital. All patients underwent clinical,
      neuropsychological, structural/functional neuroimaging, and laboratory
      evaluations. The male to female ratio was 1:1; mean age of onset was 54 years,
      and the mean duration of symptoms were 30 months. The mean scores for
      Addenbrooke's cognitive examination, Frontal Assessment Battery, and Mini-Mental
      State Examination were 70.5, 6.33 and 23.6 respectively. The mean VLOM ratio was
      2.04. MRI revealed significant asymmetrical regional frontal/temporal atrophy
      supplemented by the evidence of circumscribed hypoperfusion in SPECT imaging. We
      conclude that a combination of behavioural and cognitive assessment using short
      bedside tests, along with structural and functional neuroimaging does facilitate
      early identification, and increase the diagnostic specificity of Frontotemporal
      dementia.

PMID- 17544448
TI  - Sensory-motor and cognitive tests predict driving ability of persons with brain
      disorders.
AB  - OBJECTIVE: Brain disorders can lead to a decreased ability to perform the
      physical and cognitive functions necessary for safe driving. This study aimed to
      determine how accurately a battery of computerized sensory-motor and cognitive
      tests (SMCTests) could predict driving abilities in persons with brain disorders.
      METHODS: SMCTests and an independent on-road driving assessment were applied to
      50 experienced drivers with brain disorders referred to a hospital-based driving
      assessment service. The patients comprised 36 males and 14 females, a mean age of
      71.3 years (range 43-85 years) and diagnoses of 35 stroke, 4 traumatic brain
      injury, 4 Alzheimer's disease, and 7 other. Binary logistic regression (BLR) and
      nonlinear causal resource analysis (NCRA) were used to build model equations for
      prediction of on-road driving ability based on SMCTests performance. RESULTS: BLR
      and NCRA correctly classified 94% and 90% of referrals respectively as on-road
      pass or fail. Leave-one-out cross-validation estimated that BLR and NCRA would
      correctly predict the classification of 86% and 76% respectively of an
      independent referral group as on-road pass or fail. CONCLUSIONS: Compared with
      other studies, SMCTests have shown the highest predictive accuracy against true
      on-road driving ability as estimated in an independent data set and in persons
      with brain disorders. SMCTests also have the advantage of being able to
      comprehensively and objectively assess both sensory-motor and higher cognitive
      functions related to driving.

PMID- 17544449
TI  - Multimodal monitoring in the ICU: when could it be useful?
AB  - In the neurointensive care unit, neurologic monitoring is depended upon to signal
      the onset of neurologic decline. Many monitoring techniques such as intracranial
      pressure monitoring, cerebral perfusion pressure measurement, jugular venous
      oxygen saturation, transcranial Doppler ultrasound and continuous
      electroencephalogram are commonly practiced. Newer methods of monitoring include
      quantitative EEG, direct cerebral blood flow measurements, cerebral
      microdialysis, brain tissue oxygenation and cerebral near-infrared spectroscopy.
      When used in combination, as in multimodal monitoring, the goal is to overcome
      some of the disadvantages of each technique and to achieve a higher degree of
      accuracy in detecting secondary brain insults. However, such a large amount of
      data can be generated that such combinations have to be chosen carefully, or the
      monitoring data will not be able to be acted upon quickly enough to be of benefit
      to the patient.

PMID- 17544450
TI  - Myasthenic crisis: guidelines for prevention and treatment.
AB  - Management of myasthenic crisis (MC) requires admission of the patient into a
      neurological intensive care unit and timely institution of an efficient and safe
      treatment. Despite the growing clinical experience with disease modifying
      immunotherapy there is no clinical consensus regarding the use of plasma exchange
      or high dose immunoglobulin treatment in an ICU setting. The choice of treatment
      modalities seem to rely mostly on institutional preferences primarily due to a
      lack of well-designed clinical trials comparing currently available therapeutic
      options. In our experience and based on a review of recent literature we advocate
      the use of plasma exchange (PE) as a primary modality in the acute care setting,
      supported by other immunomodulatory medications such as corticosteroids.
      Pharmacological management cannot substitute for adequate intensive care
      management of the respiratory and bulbar insufficiency associated with MC. Every
      effort should be done to prevent myasthenic exacerbation/crisis and to develop a
      maintenance management that leads to effective prevention.

PMID- 17544451
TI  - The systemic implications of aneurysmal subarachnoid hemorrhage.
AB  - Aneurysmal subarachnoid hemorrhage (SAH) is analogous to a pathophysiological
      watershed, disrupting brain integrity and function and precipitating an array of
      systemic derangements including cardiovascular, respiratory, endocrine,
      hematological, and immune dysfunction. Extracerebral organ dysfunction is closely
      linked to the magnitude of the primary neurological insult, suggesting
      neurogenic, neuroendocrine and neuroimmunomodulatory mechanisms. Systemic organ
      involvement is associated with increased mortality and neurological impairment,
      even after adjustment for other outcome predictors such as the severity of the
      initial neurological injury. This may be a reflection of secondary brain injury
      precipitated by hypoxemia, circulatory failure, fever, or hyperglycemia, all of
      which have been linked to adverse clinical outcomes. Interventions to avert or
      reverse these and other perturbations need to be tested in clinical trials as
      they represent opportunities to improve survival and neurological recovery in
      patients with SAH.

PMID- 17544452
TI  - A search theory model of patch-to-patch forager movement with application to
      pollinator-mediated gene flow.
AB  - We present a spatially implicit analytical model of forager movement, designed to
      address a simple scenario common in nature. We assume minimal depression of patch
      resources, and discrete foraging bouts, during which foragers fill to capacity.
      The model is particularly suitable for foragers that search systematically,
      foragers that deplete resources in a patch only incrementally, and for sit-and
      wait foragers, where harvesting does not affect the rate of arrival of forage.
      Drawing on the theory of job search from microeconomics, we estimate the expected
      number of patches visited as a function of just two variables: the coefficient of
      variation of the rate of energy gain among patches, and the ratio of the expected
      time exploiting a randomly chosen patch and the expected time travelling between
      patches. We then consider the forager as a pollinator and apply our model to
      estimate gene flow. Under model assumptions, an upper bound for animal-mediated
      gene flow between natural plant populations is approximately proportional to the
      probability that the animal rejects a plant population. In addition, an upper
      bound for animal-mediated gene flow in any animal-pollinated agricultural crop
      from a genetically modified (GM) to a non-GM field is approximately proportional
      to the proportion of fields that are GM and the probability that the animal
      rejects a field.

PMID- 17544453
TI  - Nifurtimox nitroreductase activity in different cellular fractions from male rat
      pancreas. Biochemical and ultrastructural alterations.
AB  - Nifurtimox (Nfx) is a nitroheterocyclic drug used in the treatment of Chagas'
      disease. It has serious side effects which frequently force to interrupt the
      treatment. Nfx toxicity has been linked to its nitroreduction to a nitroanion
      radical with a subsequent redox cycling which generate reactive oxygen species.
      We analyzed the ability of Sprague Dawley male rat pancreas to nitroreduce Nfx
      and whether this drug may cause deleterious effects in this organ. The microsomal
      fraction exhibited Nfx nitroreductase activity in the presence of NADPH under
      anaerobic atmosphere, which was fully inhibited under air but not altered when N2
      was replaced by pure CO. The cytosol nitroreduced Nfx in the presence of
      hypoxanthine under N2; it was inhibited by allopurinol and negligible in
      aerobiosis. Nfx reached pancreatic tissue at 1, 3 or 6 h after intragastric
      administration (100 mg/kg). Six hours after drug administration, a significant
      increase in t-buthylhydroperoxide promoted chemiluminiscence was detected.
      Pancreatic protein sulfhydryl content significantly decreased at either 1, 3 or 6
      h after Nfx administration. No changes in either protein carbonyl or in lipid
      hydroperoxides were observable. Ultrastructural alterations were observed in the
      endoplasmic reticulum and nuclei from acinar cells and in the insulin-containing
      granules from the pancreas. However, the seric amylase levels were not changed,
      but the blood glucose levels were slightly but significantly increased 24 h after
      Nfx administration. These studies might suggest that Nfx treatment could impose
      an increased risk to patients exposed to other insults provoking oxidative stress
      or having preexisting pathologies in the pancreas.

PMID- 17544454
TI  - A linear system of partial differential equations modeling the resting potential
      of a heart with regional ischemia.
AB  - Ischemic ST-segment shift has been modeled using scalar stationary approximations
      of the bidomain model. Here, we propose an alternative simplification of the
      bidomain equations: a linear system modeling the resting potential, to be used in
      determining ischemic TP shift. Results of 2D and 3D simulations show that the
      linear system model is much more accurate than the scalar model. This improved
      accuracy is important if the model is to be used for solving the inverse problem
      of determining the size and location of an ischemic region. Furthermore, the
      model can provide insight into how the resting potential depends on the
      variations in the extracellular potassium concentration that characterize
      ischemic regions.

PMID- 17544455
TI  - The venous graft as an effector of early angiogenesis in a fibrin matrix.
AB  - The arteriovenous loop (AV loop) model is gaining importance as a means of
      initiating and sustaining perfusion in tissue engineering constructs in vivo.
      This study represents an attempt to dissect the morphology of early
      arterialization and angiogenesis in the AV loop in a fibrin matrix with special
      focus on the interpositional venous graft (IVG) segment. An AV loop was
      constructed in 30 rats using the femoral vessels and an IVG. The AV loop was
      encased in an isolation chamber filled with a fibrin matrix. Evaluation methods
      included scanning electron microscopy (SEM) of corrosion casts, immune histology
      and micro magnetic resonance angiography (MRA). Direct luminal neovascular
      sprouting was evident between day 10 and day 14 from the vein and the IVG but not
      from the arterial segment. Arterialization of the IVG manifested itself on the
      corrosion casts as a gradual reduction in luminal caliber with onset after day 7.
      Microdissection of the microvascular replicas could demonstrate for the first
      time the presence of direct luminal sprouts from the IVG. MRA was used to display
      the shunt pattern of perfusion in the patent AV loop. From the three segments of
      the vascular axis in the AV loop the IVG is the most versatile for applications
      in the clinical as well as the experimental setting. Kinetics of angiogenesis
      warrant further investigation in the IVG.

PMID- 17544457
TI  - Partial agonist and neuromodulatory activity of S 24795 for alpha7 nAChR
      responses of hippocampal interneurons.
AB  - S 24795 evoked methyllycaconitine-sensitive inward currents in voltage-clamped
      hippocampal interneurons with maximum amplitude about 14% that of ACh-evoked
      responses. Experiments with rat alpha7 receptors expressed in Xenopus oocytes
      confirmed that S 24795 is a partial agonist of alpha7 nAChR with an EC(50) of
      34+/-11 microM and I(max) of approximately 10% relative to ACh. When 60 microM
      ACh was co-applied to alpha7-expressing oocytes along with increasing
      concentrations of S 24795, there was a progressive decrease in response compared
      to the responses to 60 microM ACh alone (IC(50) 45+/-9 microM). The positive
      allosteric modulator 5-hydroxyindole potentiated ACh- and S 24795-evoked
      responses of alpha7 receptors in both oocytes and hippocampal interneurons. In
      hippocampal slice experiments, depending on the ACh concentrations in the
      application pipette and the ratio of ACh to S 24795, co-application of S 24795
      with ACh variously increased, decreased, or had no effect on responses, compared
      to ACh alone. In order to estimate the effective dilution factor for the pressure
      application experiments, we tested alpha7 receptors in oocytes with ACh alone and
      in co-application with S 24795 at the same ratios as in the slice experiments,
      but at varying dilution factors. The pattern of interaction seen in the slice
      experiments was most closely matched under the conditions of a 3:100 dilution,
      suggesting that the pipette solution was diluted approximately 30-fold at the
      site of action. This dilution factor was consistent with the potency of ACh and S
      24795 in the oocyte expression system (EC(50)s approximately 30 microM).

PMID- 17544456
TI  - Morphine-induced changes in acetylcholine release in the interpeduncular nucleus
      and relationship to changes in motor behavior in rats.
AB  - Owing to multiple anatomical connections and functional interactions between the
      habenulo-interpeduncular and the mesolimbic pathways, it has been proposed that
      these systems could together mediate the reinforcing properties of addictive
      drugs. 18-Methoxycoronaridine, an agent that reduces morphine self-administration
      and attenuates dopamine sensitization in the nucleus accumbens in response to
      repeated morphine, has been shown to produce these effects by acting in the
      medial habenula and interpeduncular nucleus. Acetylcholine, one of the
      predominant neurotransmitters in the interpeduncular nucleus, may be a major
      determinant of these interactions. To determine if and how morphine acts in the
      interpeduncular nucleus, the effects of acute and repeated administration of
      morphine on extracellular acetylcholine levels in this brain area were assessed.
      In addition, the motor behavior of rats receiving repeated morphine
      administration was monitored during microdialysis sessions. Acutely, morphine
      produced a biphasic effect on extracellular acetylcholine levels in the
      interpeduncular nucleus such that low and high doses of morphine (i.e., 5 and
      20mg/kg i.p.) significantly increased and decreased acetylcholine levels,
      respectively. Repeated administration of the same doses of morphine resulted in
      tolerance to the inhibitory but not to the stimulatory effects; tolerance was
      accompanied by sensitization to morphine-induced changes in locomotor activity
      and stereotypic behavior. The latter results suggest that tolerance to morphine's
      effect on the cholinergic habenulo-interpeduncular pathway is related to its
      sensitizing effects on the mesostriatal dopaminergic pathways.

PMID- 17544458
TI  - Highly activated c-fos expression in specific brain regions (ependyma,
      circumventricular organs, choroid plexus) of histidine decarboxylase deficient
      mice in response to formalin-induced acute pain.
AB  - Activation of different brain regions for acute pain-related stress induced by a
      single subcutaneous injection of 4% formalin was investigated in histidine
      decarboxylase-deficient mice. Besides pain- and stress-related brain areas and
      the tuberomamillary neurons, strong Fos activation and c-fos mRNA expression were
      found in distinct brain regions and cell types, which have not been activated in
      wild type control mice. These structures include the circumventricular organs
      (organum vasculosum of the lamina terminalis, subfornical organ, area postrema),
      some of the ependymal cells along the wall of the ventricles, tanycytes in the
      third ventricle's ependyma and the median eminence, as well as in the epithelial
      cells of the choroid plexus in the lateral, third and fourth ventricles. All of
      these areas and cell types are known as compartments of the brain-blood
      cerebrospinal fluid interface. The present observations provide strong evidence
      that an acute stressor, formalin-evoked painful stimulus elicits rapid
      alterations in the activity of neuroglial elements of histidine decarboxylase
      deficient mice that are directly involved in the communication between the brain
      and the cerebrospinal fluid space.

PMID- 17544459
TI  - Differential regulation of glutamate receptor-mediated BDNF mRNA expression in
      the cerebellum and its defects in stargazer mice.
AB  - Activity-dependent regulation of BDNF expression plays important roles in
      synaptic plasticity and neuronal function. We have investigated glutamate
      receptor-mediated regulation of BDNF expression in the cerebellum of wild-type
      and stargazer (stg) mice. Both in vivo and in vitro studies revealed that BDNF
      response kinetics in the cerebellum were much delayed with reversed sensitivity
      to NMDA versus non-NMDA agonist exposures significantly different from those in
      the cortex and hippocampus of wild-type mice. In stg mice, the severely impaired
      BDNF expression was restricted to the cerebellum while responses in the forebrain
      were intact. A selective failure of BDNF mRNA response to AMPA stimulation, but
      not NMDA, was evident in cultured stg cerebellar granule cells. These results
      demonstrate that BDNF expression is differentially regulated with region-specific
      kinetics. It indicates that the BDNF expression defect in the stg cerebellum is
      attributable to the AMPA receptor defect caused by the stargazin mutation.

PMID- 17544460
TI  - Sexual experience of male rats influences anxiety-like behavior and androgen
      levels.
AB  - There is a wide body of literature to suggest that sexual experience may
      influence androgen secretion in various species, in turn, androgens may also
      influence anxiety. We hypothesized that sexual experience may alter anxiety
      behavior and secretion of endogenous androgens. Experiment 1: anxiety behavior of
      rats with a history of sexual experience was compared to that of sexually
      inexperienced, naive male rats. Sexually-experienced rats showed less anxiety
      like behavior in the open field and elevated plus maze, and exhibited increased
      plasma and hippocampal testosterone (T) levels. Experiment 2: the effects of
      recent sexual experience on anxiety behavior of sexually-experienced male rats,
      sexually-responsive but inexperienced male rats, and sexually-unresponsive,
      inexperienced male rats exposed to a receptive female immediately prior to
      testing was examined. Recent sexual experience significantly decreased anxiety
      like behavior in the open field, elevated plus maze, and the elevated zero maze
      tasks, and tended to decrease anxiety-like behavior in the light-dark task. Rats
      with recent sexual experience exhibited increased plasma and hippocampal T
      levels. Experiment 3: to examine the effect of recent sexual experience, anxiety
      behavior of rats with a history of sexual experience that received sexual
      experience with a stimulus female immediately prior to testing was compared to
      that of rats with a history of sexual experience that did not receive sexual
      experience immediately prior to behavioral testing. Experienced rats that were
      exposed to a female prior to testing showed decreased anxiety-like behavior in
      the open field, elevated plus maze, and light-dark transition tasks, and showed
      increased plasma and hypothalamic, T and 3alpha-diol, and increased hippocampal
      T. Thus, sexual experience is associated with lower levels of anxiety-like
      behavior and higher levels of androgen secretion.

PMID- 17544461
TI  - On the processing of metabolic information through metabolite-gene communication
      networks: an approach for modelling causality.
AB  - Gene-metabolite correlation networks of three independent biological systems were
      interrogated using an approach to define, and subsequently model, causality. The
      major goal of this work was to analyse how information from those metabolites,
      that displayed a rapid response to perturbation of the biological system, is
      processed through the response network to provide signal-specific adaptation of
      metabolism. For this purpose, comparison of network topologies was carried out on
      three different groups of system elements: transcription factors, other genes and
      metabolites, with special emphasis placed on those features which are possible
      sites of metabolic regulation or response propagation. The degree of connectivity
      in all three analysed gene-metabolite networks followed power-law and exponential
      functions, whilst a comparison of connectivities of the various cellular entities
      suggested, that metabolites are less involved in the regulation of the sulfur
      stress response than in the ripening of tomatoes (in which metabolites seem to
      have an even greater regulatory role than transcription factors). These findings
      reflect different degree of metabolic regulation for distinct biological
      processes. Implementing causality into the network allowed classification of
      metabolite-gene associations into those with causal directionality from gene to
      metabolite and from metabolite to gene. Several metabolites were positioned
      relatively early in the causal hierarchy and possessed many connections to the
      downstream elements. Such metabolites were considered to have higher regulatory
      potential. For the biological example of hypo-sulfur stress response in
      Arabidopsis, the highest regulatory potential scores were established for
      fructose and sucrose, isoleucine, methionine and sinapic acid. Further
      developments in profiling techniques will allow greater cross-systems
      comparisons, necessary for reliability and universality checks of inferred
      regulatory capacities of the particular metabolites.

PMID- 17544462
TI  - Comparative phytochemical and morphological analyses of three Italian Primula
      species.
AB  - The taxonomy of alpine Primula species has long been in dispute because of high
      morphologic variability and several hybridisations. In Primula species, the
      trichome height and the colour of hair-tips are usually indicated as diacritic
      characters, but in our experience this is not adequate. The present study,
      focused on Primula auricula, Primula daonensis and Primula hirsuta, therefore
      proposes the use of other morphologic trichome parameters (size and dimensional
      ratio of stalk, neck and gland head). Phytochemical investigations about the
      flavonoid composition (epicuticular and vacuolar) of leaves, as taxonomic
      markers, have also been performed. We report the isolation and identification of
      two new flavonol glycosides, isorhamnetin 3-O-(2,6-di-O-beta-D-glucopyranosyl
      beta-D-glucopyranoside) (1) and kaempferol 3-O-(2-O-alpha-L-rhamnopyranosyl-6-O
      beta-D-xylopyranosyl-beta-D-glucopyranoside) (2) and of eight known flavonoids.
      Size and dimensional ratio of the three trichome elements (stalk, neck and
      glandular head) are typical for each species analysed. The flavonoid profile well
      characterise the entities under study. Three different profiles have been
      obtained with both vacuolar and epicuticular flavonoids. The morphologic and
      phytochemical markers proposed in this work seem to be parameters which
      significatively discriminate the species under study.

PMID- 17544463
TI  - Composition, irregular terpenoids, chemical variability and antibacterial
      activity of the essential oil from Santolina corsica Jordan et Fourr.
AB  - A detailed analysis of Santolina corsica essential oil was carried out by
      combination of GC (RI), GC-MS and 13C NMR spectroscopy. After fractionation by
      column chromatography, 50 components were identified, accounting for 88.2% of the
      total amount of the oil. The chemical composition was dominated by monoterpene
      hydrocarbons, myrcene (34.6%), santolina triene (13.5%) and beta-phellandrene
      (11.7%). Beside the main compounds, we noted the occurrence of irregular mono and
      sesquiterpenes belonging to five families: santolinane, artemisane,
      chrysanthemane, lavandulane and sesquilavandulane. Three compounds, lyratyl
      butyrate, isolyratone and epi-isolyratol were isolated and their structure
      elucidated by 2D NMR. Antibacterial activity was tested against six bacteria
      strains. The essential oil was effective against Staphylococcus aureus and C.
      jejuni. Lyratol was identified as main responsive of the antibacterial activity.
      The content of lyratol was measured in 33 oil samples isolated from individual
      plants.

PMID- 17544464
TI  - Jasmonate biosynthesis in Arabidopsis thaliana requires peroxisomal beta
      oxidation enzymes--additional proof by properties of pex6 and aim1.
AB  - Jasmonic acid (JA) is an important regulator of plant development and stress
      responses. Several enzymes involved in the biosynthesis of JA from alpha
      linolenic acid have been characterized. The final biosynthesis steps are the beta
      oxidation of 12-oxo-phytoenoic acid. We analyzed JA biosynthesis in the
      Arabidopsis mutants pex6, affected in peroxisome biogenesis, and aim1, disrupted
      in fatty acid beta-oxidation. Upon wounding, these mutants exhibit reduced JA
      levels compared to wild type. pex6 accumulated the precursor OPDA. Feeding
      experiments with deuterated OPDA substantiate this accumulation pattern,
      suggesting the mutants are impaired in the beta-oxidation of JA biosynthesis at
      different steps. Decreased expression of JA-responsive genes, such as VSP1, VSP2,
      AtJRG21 and LOX2, following wounding in the mutants compared to the wild type
      reflects the reduced JA levels of the mutants. By use of these additional mutants
      in combination with feeding experiments, the necessity of functional peroxisomes
      for JA-biosynthesis is confirmed. Furthermore an essential function of one of the
      two multifunctional proteins of fatty acid beta-oxidation (AIM1) for wound
      induced JA formation is demonstrated for the first time. These data confirm that
      JA biosynthesis occurs via peroxisomal fatty acid beta-oxidation machinery.

PMID- 17544465
TI  - PeroxiBase: the peroxidase database.
AB  - Peroxidases (EC 1.11.1.x), which are encoded by small or large multigenic
      families, are involved in several important physiological and developmental
      processes. Analyzing their evolution and their distribution among various phyla
      could certainly help to elucidate the mystery of their extremely widespread and
      diversified presence in almost all living organisms. PeroxiBase was originally
      created for the exhaustive collection of class III peroxidase sequences from
      plants (Bakalovic, N., Passardi, F., et al., 2006. PeroxiBase: a class III plant
      peroxidase database. Phytochemistry 67, 534-539). The extension of the class III
      peroxidase database to all proteins capable to reduce peroxide molecules appears
      as a necessity. Our database contains haem and non-haem peroxidase sequences
      originated from annotated or not correctly annotated sequences deposited in the
      main repositories such as GenBank or UniProt KnowledgeBase. This new database
      will allow obtaining a global overview of the evolution the protein families and
      superfamilies capable of peroxidase reaction. In this rapidly growing field,
      there is a need for continual updates and corrections of the peroxidase protein
      sequences. Following the lack of unified nomenclature, we also introduced a
      unique abbreviation for each different family of peroxidases. This paper thus
      aims to report the evolution of the PeroxiBase database, which is freely
      accessible through a web server (http://peroxibase.isb-sib.ch). In addition to
      new categories of peroxidases, new specific tools have been created to facilitate
      query, classification and submission of peroxidase sequences.

PMID- 17544466
TI  - Smoking initiation and nicotine dependence symptoms in Ukraine: findings from the
      Ukraine World Mental Health survey.
AB  - OBJECTIVES: Cigarette smoking is a major cause of morbidity and mortality in
      former Soviet countries. This study examined the personal, familial and
      psychiatric risk factors for smoking initiation and development of nicotine
      dependence symptoms in Ukraine. STUDY DESIGN: Cross-sectional survey. METHODS:
      Smoking history and dependence symptoms were ascertained from N=1711 adults in
      Ukraine as part of a national mental health survey conducted in 2002. Separate
      analyses were conducted for men and women. RESULTS: The prevalence of lifetime
      regular smoking was 80.5% in men and 18.7% in women, with median ages at
      initiation among smokers of 17 and 18, respectively. Furthermore, 61.2% of men
      and 11.9% of women were current smokers; among the subgroup of lifetime smokers,
      75.9% of men and 63.1% of women currently smoked. The youngest female cohort
      (born 1965-1984) was 26 times more likely to start smoking than the oldest.
      Smoking initiation was also linked to childhood externalizing behaviors and
      antecedent use of alcohol in both genders, as well as marital status and personal
      alcohol abuse in men, and childhood urbanicity and birth cohort in women.
      Dependence symptoms developed in 61.7% of male and 47.1% of female smokers. The
      rate increased sharply in the first four years after smoking initiation.
      Dependence symptoms were related to birth cohort and alcohol abuse in both
      genders, as well as growing up in a suburb or town and childhood externalizing
      behaviors in men, and parental antisocial behavior in women. CONCLUSIONS:
      Increased smoking in young women heralds a rising epidemic in Ukraine and
      underscores the need for primary prevention programs, especially in urban areas.
      Our findings support the importance of childhood and alcohol-related risk
      factors, especially in women, while pre-existing depression and anxiety disorders
      were only weakly associated with starting to smoke or developing dependence
      symptoms.

PMID- 17544467
TI  - Obesity and health in Europeans aged 50 years and older.
AB  - BACKGROUND: Obesity is increasing globally across all population groups. Limited
      data are available on how obesity patterns differ across countries. OBJECTIVE: To
      document the prevalence of obesity and related health conditions for Europeans
      aged 50 years and older, and to estimate the association between obesity and
      health outcomes across 10 European countries. METHODS: Data were obtained from
      the 2004 Survey of Health, Ageing and Retirement in Europe, a cross-national
      survey of 22,777 Continental Europeans over the age of 50 years. The health
      outcomes included self-reported health, disability, doctor-diagnosed chronic
      health conditions and depression. Multivariate regression analysis was used to
      predict health outcomes across weight classes (defined by body mass index [BMI]
      from self-reported weight and height) in the pooled sample and individually in
      each country. RESULTS: The prevalence of obesity (BMI >or=30) ranged from 12.8%
      in Sweden to 20.2% in Spain for men and from 12.3% in Switzerland to 25.6% in
      Spain for women. Adjusting for compositional differences across countries changed
      little in the observed large heterogeneity in obesity rates throughout Europe.
      Compared with normal weight individuals, men and women with greater BMI had
      significantly higher risks for all chronic health conditions examined except
      heart disease in overweight men. Depression was linked to obesity in women only.
      Particularly pronounced risks of impaired health and chronic health conditions
      were found among severely obese people. The effects of obesity on health did not
      vary significantly across countries. CONCLUSIONS: Cross-country differences in
      the prevalence of obesity in older Europeans are substantial and exceed socio
      demographic differentials in excessive body weight. Obesity is associated with
      significantly poorer health outcomes among Europeans aged 50 years and over, with
      effects similar across countries. Large heterogeneity in obesity throughout
      Europe should be investigated further to identify areas for effective public
      policy.

PMID- 17544468
TI  - Population downsizing.

PMID- 17544469
TI  - Unravelling the neuropathogenesis of Japanese encephalitis.
AB  - Japanese encephalitis is a devastating disease that causes a frequently fatal
      encephalitis and is a major health problem throughout much of Asia. Mortality
      rates can be as high as 30%, with one-third of survivors suffering severe
      neurological sequelae. Viral cytopathology is important, but the contribution of
      blood-brain barrier breakdown, the inflammatory response and bystander cell death
      are unknown. Studies that address the mechanisms producing neuronal dysfunction
      and damage are required, including the examination of autopsy tissues. A better
      understanding of these mechanisms may lead to therapeutic strategies to reduce
      brain injury and neurological sequelae.

PMID- 17544470
TI  - Arithmetic or geometric means of eggs per gram are not appropriate indicators to
      estimate the impact of control measures in helminth infections.
AB  - In helminthology, the mean number of eggs per gram of faeces (EPG) is a commonly
      used indicator for the severity of the infection in a population. The example
      presented here shows that, in my opinion, mean EPG (either calculated as
      arithmetic or geometric means) is not the best way to evaluate the impact of
      control measures, as helminth infections present an intensity/morbidity
      relationship, which should be considered when selecting indicators for the
      evaluation of control measures. In my opinion, an analysis by class of intensity
      is more informative.

PMID- 17544471
TI  - Ultrastructural detection of proteins, lipids and carbohydrates in oocytes of
      Amblyomma triste (Koch, 1844) (Acari; Ixodidae) during the vitellogenesis
      process.
AB  - The ovary of the tick Amblyomma triste is classified as panoistic, which is
      characterized by the presence of oogonia without nurse and follicular cells. The
      present study has demonstrated that the oocytes in all developmental stages (I
      IV) are attached to the ovary through a pedicel, a cellular structure that
      synthesizes and provides carbohydrate, lipids and proteins supplies for the
      oocytes during the vitellogenesis process. The lipids are deposited during all
      oocyte stages; they are freely distributed as observed in stages II, III and IV
      or they form complexes with other elements. The proteins are also deposited in
      all stages of the oocytes, however, in lower concentration in the stage IV. There
      is carbohydrate deposition from oocytes in the stage II as well as in stages III
      and IV. In addition, the present work has demonstrated that the oocyte yolk of A.
      triste has a glycolipoprotein nature and the elements are deposited in the
      following sequence: firstly the lipids and proteins, and finally the
      carbohydrates.

PMID- 17544472
TI  - Biodegradation of organonitriles by adapted activated sludge consortium with
      acetonitrile-degrading microorganisms.
AB  - A microbial process for the degradation of three types of structurally distinct
      organonitriles (i.e., saturated and unsaturated aliphatic nitrile and aromatic
      nitrile) was studied. Microorganisms were enriched from the activated sludge of a
      pharmaceutical wastewater treatment plant and adapted through providing
      acetonitrile as the sole carbon and nitrogen source for their growth. The adapted
      mixed culture was then examined for their capability of degrading acetonitrile,
      acrylonitrile and benzonitrile under various operational conditions. The
      performance of biodegradation and the metabolic intermediate- and end-products in
      the process were monitored. The results show that an average removal rate of
      0.083 g acetonitrile g(-1)-VSS h(-1), 0.0074 g acrylonitrile g(-1)-VSS h(-1) or
      0.0029 g benzonitrile g(-1)-VSS h(-1) was achieved in the batch bioreactor under
      the common operational condition of 25 degrees C and pH 7. The biodegradation of
      acetonitrile and acrylonitrile showed a two-step pathway, with the generation of
      acetamide followed by acetic acid and ammonia for acetonitrile or acrylamide
      followed by acrylic acid and ammonia for acrylonitrile. However, the
      biodegradation of benzonitrile appeared to have only one step, with the direct
      production of benzoic acid and ammonia, but without benzamide being detected in
      the process. The results suggest that, depending on the substrates, the adapted
      mixed culture can develop very different degradation pathways, such as nitrile
      hydratase plus amidase for acetonitrile or acrylonitrile and nitrilase for
      benzonitrile. Therefore, the adapted mixed culture has a great potential and
      flexibility for actual applications in biodegradation of various organonitrile
      compounds.

PMID- 17544473
TI  - Detection of Legionella spp. and some of their amoeba hosts in floating biofilms
      from anthropogenic and natural aquatic environments.
AB  - Floating biofilms develop at the water-air interface and harbor numerous
      microorganisms, some of which are human pathogens like Legionella pneumophila.
      The presence of Legionella spp. and especially L. pneumophila in such biofilms
      was investigated. In parallel, the occurrence of Naegleria spp., Acanthamoeba
      spp., Willaertia spp., Vahlkampfia spp. and Hartmanella spp. was determined and
      it was examined whether Acanthamoeba spp. isolates were naturally infected with
      L. pneumophila bacteria. Eight anthropogenic and 37 natural aquatic environments
      were sampled between June and August 2005. Both Legionella spp. and L.
      pneumophila were present in 100% of the floating biofilms of the anthropogenic
      aquatic systems. Eighty-one percent of all natural floating biofilm samples were
      positive for Legionella spp. and 70% of these samples were positive for L.
      pneumophila. Legionella concentrations were in the range of 10(1)
      10(2)cells/cm(2). Naegleria spp. and Acanthamoeba spp., two well-known L.
      pneumophila amoeba hosts, were present in 50-92% and 67-72% of floating biofilm
      samples, respectively. Acanthamoeba spp. isolates appeared to be naturally
      infected with L. pneumophila bacteria as proved by fluorescent in situ
      hybridization.

PMID- 17544474
TI  - Potential nitrate removal in a coastal freshwater sediment (Haringvliet Lake, The
      Netherlands) and response to salinization.
AB  - Nitrogen transformations and their response to salinization were studied in
      bottom sediment of a coastal freshwater lake (Haringvliet Lake, The Netherlands).
      The lake was formed as the result of a river impoundment along the south-western
      coast of the Netherlands, and is currently targeted for restoration of estuarine
      conditions. Nitrate porewater profiles indicate complete removal of NO(3)(-)
      within the upper few millimeters of sediment. Rapid NO(3)(-) consumption is
      consistent with the high potential rates of nitrate reduction (up to 200 nmol N
      cm(-3) h(-1)) measured with flow-through reactors (FTRs) on intact sediment
      slices. Acetylene-block FTR experiments indicate that complete denitrification
      accounts for approximately half of the nitrate reducing activity. The remaining
      NO(3)(-) reduction is due to incomplete denitrification and alternative reaction
      pathways, most likely dissimilatory nitrate reduction to NH(4)(+) (DNRA). Results
      of FTR experiments further indicate that increasing bottom water salinity may
      lead to a transient release of NH(4)(+) and dissolved organic carbon from the
      sediment, and enhance the rates of nitrate reduction and nitrite production.
      Increased salinity may thus, at least temporarily, increase the efflux of
      NH(4)(+) from the sediment to the surface water. This work shows that salinity
      affects the relative importance of denitrification compared to alternative
      nitrate reduction pathways, limiting the ability of denitrification to remove
      bioavailable nitrogen from aquatic ecosystems.

PMID- 17544475
TI  - Effects of bacterial activity on estrogen removal in nitrifying activated sludge.
AB  - The effects of bacterial activity on the degradation of estrone (E1), estradiol
      (E2), estriol (E3) and ethinylestradiol (EE2) in nitrifying activated sludge
      (NAS) were studied with different substrates and organic loading rates (OLRs) and
      low temperature conditions. Heterotroph was shown to have utilized glucose prior
      to E1 for metabolism. The co-metabolism of ammonia oxidizing bacteria (AOB)
      dominated the degradation of E1, E2 and EE2 in NAS. The higher the organic
      loading, the higher the rate of organic matter transformation, with less ammonia
      oxidation and less degradation of E1, E2 and EE2. The degradation of E3 in NAS
      was shown to be largely due to heterotroph metabolism. On the basis of the
      difference of apparent activity between heterotroph and AOB at 4 degrees C, the
      process of estrogen degradation via the co-metabolism of AOB was able to be
      identified.

PMID- 17544476
TI  - Effect of aluminium sulphate on interactions between silica surfaces studied by
      atomic force microscopy.
AB  - Surface interaction forces between different types of silica surfaces (pure
      silica beads, borosilicate glass beads, polished silicon wafers and fused silica
      slides) were measured by atomic force microscopy (AFM) in solutions of aluminium
      sulphate (alum) in order to understand the role of hydrated aluminium species on
      the coagulation of negatively charged oxide colloids in drinking water treatment.
      The alum coagulant concentration used in this study was 150 microM aluminium. The
      alum solutions were prepared from analytical grade Al2(SO4)3.16H2O. It was found
      that the presence of aluminium sulphate at a concentration close to the values
      typically used in industrial scale water treatment applications generally induced
      strong, long-range repulsive forces between the various types of surfaces
      studied. At this alum concentration streaming potential measurements indicated
      reversal in the sign of the surface charge. It was also found that whenever
      borosilicate glass beads were used, the interaction force became strongly
      attractive when the AFM cell was flushed with deionised water. It was argued that
      this attraction occurred because of the charge nonuniformity of the aluminium
      hydrates adsorbed at the glass surface. A mechanism was proposed to explain the
      observed interaction phenomena based on the deduced microstructure of the
      adsorbed surface layers and to rationalise the new findings for applications in
      drinking water treatment.

PMID- 17544477
TI  - Quantity and spectroscopic properties of soil dissolved organic matter (DOM) as a
      function of soil sample treatments: air-drying and pre-incubation.
AB  - The dissolved organic matter (DOM) in soils is essentially defined by the way in
      which it is obtained. Therefore, we need to understand as to how pre-treatment of
      a soil will affect the characteristics of DOM, since this fraction may be
      strongly influenced by a soil's water content. The effect of two different pre
      treatments on DOM from the A-horizons of a large variety of ecosystems and
      regions were compared. In both cases the soils were allowed to air-dry. In one
      case the air-dried soil was directly extracted (AD), while in the other case it
      was preincubated for 1 week at 50% of its water holding capacity (INCU). AD is
      simpler, but INCU brings the soil, and especially its microbial population, back
      to a standardised state, which is more representative of the usual state in the
      field. Both methods are used whenever an adjustment of the soil water content is
      essential to compare different regions or to eliminate short term weather
      effects. A significant regression indicated that the dissolved organic carbon
      (DOC) extracted from INCU samples was only 20% of AD DOC. Both the absorptivity
      (UV absorption divided by DOC) of 86% of the samples, and a fluorescence emission
      spectrum based Humification Index in all cases increased as a result of
      preincubation. This would indicate that labile compounds released during drying
      were metabolised during the incubation. However, the magnitude of this increase
      varied, and no correlation with soil organic and microbial carbon, pH, or texture
      could be detected. The results show that DOM extracted from AD and INCU soils is
      not comparable and that the differences are mainly due to the impact of air
      drying on the microbial activity.

PMID- 17544478
TI  - Chemical characterization and effects on Lepidium sativum of the native and
      bioremediated components of dry olive mill residue.
AB  - Dry olive mill residue (DOR) from the olive oil production by two phase
      centrifugation system was fractionated by a consecutive continuous solid-liquid
      extraction obtaining the EAF, PF, MF and WF fractions with ethyl acetate, n
      propanol, methanol and water, respectively. The chemical, chromatographic and
      mass spectrometric analyses showed EAF, PF and MF to be mainly composed of simple
      phenols, phenolic acids, flavonoids and glycosilated phenols (glycosides of
      phenols, secoiridoids and flavonoids), whereas WF was mainly consisting of
      polymerin, the metal organic polymeric mixture previously identified in olive oil
      mill waste waters and composed of carbohydrates, melanin, proteins and metals (K,
      Na, Ca, Mg and Fe). The identification in DOR of oleoside, 6'-beta-glucopyranosyl
      oleoside and 6'-beta-rhamnopyranosyl-oleoside, and of its organic polymeric
      component, known as polymerin, are reported for the first time in this paper. The
      inoculation of the previously mentioned fractions with saprobe fungi Coriolopsis
      rigida, Pycnoporus cynnabarinus or Trametes versicolor indicated these fungi to
      be able to metabolize both the phenols and glycosilated phenols, but not
      polymerin. In correspondence, EAF, PF, MF and WF, which proved to be toxic on
      Lepidium sativum, decreased their toxicity after incubation with the selected
      fungi, WF showing to be also able to stimulate the growth of the selected seeds.
      The phytotoxicity appeared mainly correlated to the monomeric phenols and, to a
      lesser extent, to the glycosilated phenols, whereas polymerin proved to be non
      toxic. However, the laccase activity was not associated with the decrease of
      phytotoxicity. The valorization of DOR as a producer of high added value
      substances of industrial and agricultural interest in native form and after their
      bioremediation for a final objective of the total DOR recycling is also
      discussed.

PMID- 17544479
TI  - Hazardous air pollutants in industrial area of Mumbai - India.
AB  - Hazardous Air Pollutants (HAPs) have a potential to be distributed into different
      component of environment with varying persistence. In the current study fourteen
      HAPs have been quantified in the air using TO-17 method in an industrial area of
      Mumbai. The distribution of these HAPs in different environmental compartments
      have been calculated using multi media mass balance model, TaPL3, along with long
      range transport potential and persistence. Results show that most of the target
      compounds partition mostly in air. Phenol and trifluralin, partition
      predominantly into soil while ethyl benzene and xylene partition predominantly
      into vegetation compartment. Naphthalene has the highest persistence followed by
      ethyl benzene, xylene and 1,1,1 trihloro ethane. Long range transport potential
      is maximum for 1,1,1 trichloroethane. Assessment of human health risk in terms of
      non-carcinogenic hazard and carcinogenic risk due to exposure to HAPs. have been
      estimated for industrial workers and residents in the study area considering all
      possible exposure routes using the output from TaPL3 model. The overall
      carcinogenic risk for residents and workers are estimated as high as unity along
      with very high hazard potential.

PMID- 17544480
TI  - The application of positive matrix factorization in the analysis,
      characterisation and detection of contaminated soils.
AB  - Multivariate factor analytical techniques are widely used for the approximation,
      in terms of a linear combination of factors, of multivariate experimental data.
      The chemical composition of soil samples are multivariate in nature and provide
      datasets suitable for the application of these statistical techniques. Recent
      developments of multivariate factor analytical techniques have led to the
      approach of Positive Matrix Factorization (PMF), a weighted least squares fit of
      a data matrix in which the weights are determined depending on the error
      estimates of each individual data value. This approach relies on more physically
      significant assumptions than methods like Principal Components Analysis which is
      frequently used in the analysis of soil datasets. In this paper we apply PMF to
      characterise the pollutant source in a set of geographically referenced soil
      samples taken within a 200 m radius of a site characterised by a high
      concentration of heavy metals. Each sample has been analysed for major and minor
      elements (using wavelength-dispersive X-ray fluorescence spectrometry), carbon,
      hydrogen and nitrogen (using a CHN elemental analyzer) and mercury (using cold
      vapour atomic absorption spectrometry). Analysis of the soils using PMF resulted
      in a successful partitioning of variances into sources related to background soil
      geochemistry, organic influences and those associated with the contamination.
      Combining these results with a geostatistical approach successfully demarcated
      the main source of the combined organic and heavy metal contamination.

PMID- 17544481
TI  - Photodecomposition of o-cresol by UV-LED/TiO2 process with controlled periodic
      illumination.
AB  - This study investigated the effect of controlled periodic illumination on the
      photonic efficiency and temporal decomposition behavior of o-cresol by UV/TiO2
      process in a slurry reactor using light emitting diodes as the light source.
      Based on the same UV light intensity of 6.7 W m(-2), the calculated photonic
      efficiencies increased from 1.5% to 6.3% with the decreasing duty cycle from 1.0
      to 0.1 possibly ascribed to the decreasing electron-hole recombination. Actually,
      the calculated photonic efficiency under periodic illumination at sufficiently
      intermittence was inferior to, but approached, those under continuous
      illumination at equivalent average UV light intensity. The calculated electric
      energy per order increased from 32 to 37 k W h m(-3)order(-1) for experiments
      conducted with the increasing duty cycle from 0.1 to 1.0, and the electric energy
      consumption decreased significantly due to the lower duty cycle and average UV
      light intensity. The photocatalytic decomposition of o-cresol with the UV-light
      emitting diodes light could be well modeled by the Langmuir-Hinshelwood kinetic
      equation.

PMID- 17544482
TI  - Long-term visibility trends in one highly urbanized, one highly industrialized,
      and two rural areas of Taiwan.
AB  - Visibility trends on the island of Taiwan were investigated employing visibility
      and meteorological (1961-2003), and air pollutant (1994-2003) data from one
      highly urbanized center (Taipei), one highly industrialized center (Kaohsiung),
      and two rural centers (Hualien and Taitung). Average annual visibility (1961
      2003) was significantly higher at the rural centers. Unlike at the other centers,
      visibility in Taipei improved between 1992 (6.6 km) and 2003 (9.9 km), and this
      can be linked to the construction and expansion of a mass transit rail system in
      Taipei, the use of which has helped reduce emissions of traffic related air
      pollutants, particles, and NO2. This has left Kaohsiung with the lowest annual
      visibility since 1994, despite its 1961-2003 average being superior to that of
      Taipei. Precipitation lowers visibility, as demonstrated by the all-centers
      correlation coefficient for visibility and precipitation of -0.92. Hence,
      frequency of precipitation is one of the factors contributing to the average
      annual visibility number. The poorest air quality category ('episode'), most
      commonly experienced in Taipei and Kaohsiung, was characterized by relatively
      high concentrations of PM10 and NOx at those centers, with comparatively high
      atmospheric pressure and comparatively low visibility and wind speed. Excepting
      O3, pollutant concentrations were slightly higher during weekdays, although there
      was no consistent, significant difference in weekday-weekend visibility.
      Principal component analysis demonstrated that visibility was markedly reduced in
      Taipei, Kaohsiung, and Hualien by increased vehicular emissions, road traffic
      dust, and industrial activity, but not in Taitung, where visibility was as a
      result superior to that at the other centers and degradation in visibility was
      likely a response to long-range transport of pollutants rather than local
      sources. Optimal empirical regression models indicated a negative impact on
      visibility for each of PM10, SO2 and NO2, particularly so for PM10, and validity
      of these models for Taipei, Kaohsiung, and Hualien was confirmed by correlation
      coefficients of simulated and observed average visibility of 0.63-0.72 for daily
      visibility and 0.85-0.88 for monthly visibility. For Taitung these figures were
      only 0.46 and 0.50, respectively, indicating that simulations for Taitung should
      include long-range transport as a pollutant source.

PMID- 17544483
TI  - Health risk assessment for traffic policemen exposed to polycyclic aromatic
      hydrocarbons (PAHs) in Tianjin, China.
AB  - In China, traffic policemen have to stand for several hours a day at the road
      intersections with high vehicle flows. To assess their exposure to airborne
      carcinogenic polycyclic aromatic hydrocarbons (PAHs) during their working time, a
      preliminary study was conducted to measure the personal exposure level to PAHs.
      And a probabilistic incremental lifetime cancer risk (ILCR) model together with
      the benzo[a]pyrene (BaP) toxic equivalents (BaP(eq)) method was used to conduct
      health risk assessment. Personal exposure monitors (PEM) were carried by traffic
      policemen to collect PM10 samples during their daily work in Tianjin, China.
      Meanwhile, PM100 samples were collected at the roadsides and on campus of Nankai
      University as comparison. PAHs species were quantitatively analyzed by GC/MS.
      Experimental results showed that the concentrations of total PAHs, BaP and
      BaP(eq) were much higher at the road intersections (867.5, 26.2, 82.4 ng m(-3)),
      where the traffic policemen stand during their work time, than those at the
      roadsides (46.6, 1.5, 5.7 ng m(-3)), and on campus (19.5, 0.7, 2.4 ng m(-3)).
      According to the risk assessment results, the occupational risk falls within the
      range from 10(-6) to 10(-3). On the basis of sensitivity analysis results,
      further research should be directed to give better characterization of the yearly
      concentration distribution of PAHs and the cancer slope factor (CSF) of BaP in
      order to improve the accuracy of the health risk assessment.

PMID- 17544484
TI  - Potential impact of former Zn ore extraction activities on dissolved uranium
      distribution in the Riou-Mort watershed (France).
AB  - The industrial basin of Decazeville (Riou-Mort watershed, South-West France) is
      well known for its heavy metal pollution and its subsequent environmental effects
      on the Lot-Garonne River system. The source of this pollution is the Riou-Mort
      River, which drains smelting waste areas. A first survey after remediation works
      has revealed elevated dissolved uranium (U(D)) concentrations in the outlet of
      the Riou-Mort River. The objective of this research is to identify the origin of
      U(D) in the Riou-Mort watershed and to evaluate the impact of industrial
      activities on this element. Uranium was measured at 10 water sampling sites,
      located upstream and downstream the industrial basin, and in three smelting waste
      deposits. Uranium concentrations in the smelting waste deposits reach up to 14.4
      mg kg(-1) and (234U/238U) activity ratios (AR) are near unity. Dissolved U
      concentrations in the Riou-Mort River and its main tributaries ranges over two
      orders of magnitude from 0.02 to 6.1 microg L(-1). The highest levels were
      measured in a site with no anthropogenic pollution, upstream from the industrial
      area. This observation suggests that U(D) is mainly linked to weathering; the
      elevated U concentrations originate from the naturally occurring radioactive
      materials (NORM) located in the Permian bedrock and no significant U pollution
      exists, at present, in the Riou-Mort watershed. This work demonstrates that
      spatial monitoring coupled with a long time-series are an essential prerequisite
      in assessment of spatiotemporal variations of U(D), prior to a diagnostic of
      pollution in a small watershed.

PMID- 17544485
TI  - A recombinant protein and a chemically synthesized peptide containing the active
      peptides of the platelet collagen receptors inhibit ferric chloride-induced
      thrombosis in a rat model.
AB  - We have previously reported that a recombinant protein (M(r) 47 kDa), which
      contains both active peptide of platelet receptors for types I and III collagen
      inhibits both types I and III collagen-induced platelet aggregation. In order to
      eliminate non-reactive portion of the protein, we have constructed a recombinant
      of rHyB (M r 6 kDa). In addition, we chemically synthesized a hybrid peptide with
      30 amino acid residues (cHyB, M r 3 kDa) that contains each of the active peptide
      derived from platelet receptors for types I and III collagen and a linker of 12
      amino acid residues. In the present investigation, we report that both rHyB and
      cHyB inhibit type I and type III collagen-induced platelet aggregation, and the
      adhesion of radiolabeled platelets onto rabbit aortic segments in a dose
      dependent manner. We have used an animal model, which employs FeCl3 to induce
      thrombi formation to study the effectiveness of both rHyb and cHyB on preventing
      thrombi formation. We obtained results that show that both rHyB and cHyB can
      inhibit thrombi formation in a dose-dependent manner. These results suggest that
      either rHyB or cHyB may be a possible therapeutic agent in preventing thrombi
      formation.

PMID- 17544487
TI  - Photodynamic effects of SIM01, a new sensitizer, on experimental brain tumors in
      rats.
AB  - BACKGROUND: Glioblastomas are the third most common cause of cancer death in
      patients between 15 and 35 years old. Literature suggests that PDT could
      represent a promising treatment, providing that sensitizers could accumulate
      within the cancer tissues despite the blood-brain barrier. METHODS: Distribution
      and PDT effect of SIM01, a promising photosensitizer, have been evaluated on
      orthotopic C6 tumor model in rats by comparison with HPD and m-THPC.
      Pharmacokinetics had been analyzed with fluorescence and ROS. Photodynamic
      treatment was done using a 630-nm light with an energy density of 100 J cm(-2)
      for HPD and a 652-nm light with an energy density of 20 J cm(-2) for m-THPC and
      SIM01. RESULTS: The correlation between fluorescence and ROS dosimetry was found
      to be excellent. An optimal concentration was found after 12 hours for SIM01 (4
      mg/kg), 24 hours for HPD (10 mg/kg), and 48 hours for m-THPC (4 mg/kg). The best
      normal tissue/cancer ratio of concentration had been found after 12 hours for
      SIM01 and 48 hours for HPD and m-THPC. Pathological examinations after PDT showed
      that the criteria for histology of glioblastic origin were absent in SIM01
      treated rats 12 hours after injection but were present in 50% of rats treated 24
      hours after injection and in all after a 48-hour delay. Mean survival of rats
      treated 12 or 24 hours after SIM01 injection was significantly improved compared
      with controls, HPD-, or m-THPC-treated groups. Survival of rats treated 12 or 24
      hours after SIM01 injection reached 20 days but decreased for longer delays. On
      the contrary, survival reached 18 days at the maximum for rats treated 48 hours
      after m-THPC or HPD injection. CONCLUSIONS: Our results confirm that PDT is a
      promising treatment for glioblastomas. SIM01 efficacy is as efficient as m-THPC
      but with much more favorable pharmacokinetics.

PMID- 17544488
TI  - Spontaneous twiddler's syndrome in a patient with a deep brain stimulator.
AB  - BACKGROUND: The subcutaneous placement of IPGs with electrodes to various
      intracranial and extracranial sites for the purpose of controlling conditions
      such as essential tremor, epilepsy, Parkinson's disease, and pain is increasing.
      Experience with similar placement of cardiac pacemakers and defibrillators had
      revealed the possibility of generator migration and subsequent lead fracture
      either spontaneously or, more often, through a patient's conscious or
      subconscious manipulation of the device through the skin. This phenomenon has
      been termed twiddler's syndrome. CASE DESCRIPTION: An elderly patient's IPG used
      in the treatment of a debilitating essential tremor had spontaneously rotated
      during the course of normal physical activities. This resulted in the twisting
      and fracturing of the leads. Torsional displacement of and tissue stress on
      subauricular lead connectors caused early discomfort in that region. Recurrent
      tremors occurred upon device failure. Surgical replacement of the IPG lead and
      use of a polyester pouch sutured to the surrounding fascia were observed to
      correct the problem. CONCLUSION: Those caring for patients, especially elderly
      and obese patients, with an IPG should be aware of the potential of device
      failure as a result of spontaneous twiddler's syndrome.

PMID- 17544490
TI  - Impact of p53 immunostaining in predicting advanced or recurrent placental site
      trophoblastic tumors: a study of 12 cases.
AB  - OBJECTIVES: To identify an indicator that can predict tumor cell spread beyond
      the uterine corpus. METHODS: We studied clinicopathology and immunohistochemistry
      of 12 cases of PSTT. Two cases of epithelioid trophoblastic tumor (ETT) were
      included as reference cases. For immunohistochemistry, antibodies against Ki-67,
      p53, human chorionic gonadotropin (hCG), human placental lactogen (hPL),
      carcinoembryonic antigen (CEA, polyclonal antibodies; pCEA), carcinoembryonic
      antigen-related cellular adhesion molecule 1 (CEACAM1), and bcl-2 were used. PSTT
      cases were divided as confined and non-confined groups (CG and NCG,
      respectively). CG consisted of stage I cases with no evidence of recurrence
      during the follow-up, while NCG consisted of either advanced (stage II or higher)
      or recurrent stage I lesions. RESULTS: Age, the interval from the latest
      pregnancy, serum hCG/hPL levels, tumor size, mitotic figures, Ki-67 labeling
      indices, and bcl-2 did not discriminate NCG from CG. CEACAM1 and CEA-related
      antigens as determined by polyclonal anti-CEA antibodies were specifically
      stained in PSTT cells, but they could not discriminate groups. p53 was positive
      in PSTT cells in NCG (6/6, 100%), while it was positive in only one case of CG
      (1/6, 16.7%), indicating a possible usefulness of p53 immunostaining in
      predicting an invasive or recurrent propensity of PSTT cells (p=0.015).
      CONCLUSIONS: This finding also suggests the importance of p53 function in the
      biology of PSTT cells.

PMID- 17544492
TI  - Protein kinase Czeta: a novel protective neonatal T-cell marker that can be
      upregulated by allergy prevention strategies.
AB  - BACKGROUND: Variations in neonatal T-cell function have been associated with
      allergic disease. OBJECTIVES: To examine the relationship between neonatal T-cell
      protein kinase (PKC) expression and subsequent allergic disease. METHODS: T cells
      were purified from cord blood samples (n = 74) obtained from a cohort of mothers
      who received either 4 g/d fish oil or a placebo from 20 weeks of gestation. PKC
      expression was examined in relationship to supplementation, fatty acid levels,
      cytokine production, and allergic outcomes at 1 year and 2.5 years of age.
      RESULTS: Neonatal T-cell PKCzeta expression was lower in children who had
      evidence of allergic disease at 1 year (P = .001) and 2.5 years (P = .052) of
      age. It was also lower in children with sensitization (positive skin prick test)
      at each age (P = .02 and P = .072, respectively). PKCzeta expression was
      inversely correlated to PKCalpha (r = -0.28; P = .025), which was strongly
      related to IL-5 responses to allergens (ovalbumin, r = 0.59; P = .003; dust mite,
      r = 0.52; P = .011) at 1 year of age. Fish oil supplementation was associated
      with significantly higher PKCzeta expression (P = .014), whereas most other
      isozymes were reduced by fish oil supplementation. CONCLUSION: This is the first
      study to show that allergic disease is associated with altered expression of T
      cell PKC isozymes in the neonatal period. It has also demonstrated that fish oil
      can modulate expression of PKC isozymes in a potentially favorable direction.
      CLINICAL IMPLICATIONS: Protein kinase Czeta should be explored further as an
      early marker and potential target for disease prevention.

PMID- 17544491
TI  - Evaluation of estradiol administration on the discriminative-stimulus and subject
      rated effects of d-amphetamine in healthy pre-menopausal women.
AB  - Accumulating evidence suggests that estradiol might be responsible for the
      enhanced response to psychostimulants sometimes observed in females. In this
      study, 10 healthy pre-menopausal women who were using oral, hormone-based birth
      control learned to discriminate 15 mg/70 kg oral d-amphetamine from placebo. Once
      a discrimination criterion was met (i.e., >or=80% correct responding at the final
      time point for five consecutive sessions), a range of doses of oral d-amphetamine
      (0, 3.125, 7.5 and 15 mg/70 kg) was tested alone and in combination with
      sublingual estradiol (0 and 0.25 mg). Test sessions were conducted during the
      oral contraception placebo phase when levels of both estradiol and progesterone
      were at their lowest. d-Amphetamine functioned as a discriminative stimulus and
      produced prototypical stimulant effects (e.g., increased positive subject-rated
      drug effects, elevated cardiovascular measures). Estradiol enhanced the
      discriminative-stimulus effects of the low dose, but not higher doses of d
      amphetamine. Estradiol also enhanced d-amphetamine effects on a subset of self
      report ratings (i.e., VAS Like Drug and total score on the Stimulant subscale of
      the Adjective-Rating Scale). These findings provide limited support for the
      notion that estradiol increases sensitivity to the psychostimulant effects of
      drugs such as d-amphetamine.

PMID- 17544493
TI  - Pneumococcal conjugate vaccine is immunogenic in lung fluid of HIV-infected and
      immunocompetent adults.

PMID- 17544494
TI  - Vitrification of in vitro cultured porcine two-to-four cell embryos.
AB  - The objective of this experiment was to evaluate the effect of a 5-day period of
      in vitro culture of two-to-four cell porcine embryos up to the blastocyst stage
      on their ability to survive vitrification and warming. In order to increase the
      cooling rate, superfine open pulled straws and Vit-Master((R)) technology were
      used for vitrification. Two-to-four cell embryos were collected from weaned sows
      (n=11) on day 2 (D0=onset of estrus). Some embryos (N=63) were vitrified within
      3h after collection, warmed and cultured for 120h (Group V2). Additionally, 81
      two-to-four cell embryos were cultured for 96h in order to obtain blastocysts;
      these were then vitrified, warmed and cultured for 24h (Group VB; N=65). The
      remaining two-to-four cell embryos were used as controls and thus not vitrified
      (control embryos; N=70) but were cultured in vitro for 120h. The V2, VB and
      control embryos were evaluated for their developmental progression and morphology
      during culture. All embryos (V2, VB and controls) were fixed on the same day of
      development in order to assess the total number of blastomeres. The survival and
      blastocyst formation rates obtained from V2 embryos were very poor (9.6+/-0.7%
      and 3.2+/-0.5%, respectively). The survival and hatching rates of VB embryos
      (75.0+/-0.69% and 33.6+/-0.13%) were lower (p<0.001) than those obtained with
      control embryos (89.1+/-0.8% and 47.5+/-0.12%). Hatched VB embryos had a lower
      (p<0.01) total cell number than hatched control embryos (70.3+/-4.5 versus 90.6+/
      3.2, respectively). There was no difference between expanded VB and control
      blastocysts. In conclusion, blastocysts derived from in vitro culture of two-to
      four cell pig embryos could be successfully vitrified using SOPS straws and Vit
      Master.

PMID- 17544495
TI  - Interhemispheric cooperation and non-cooperation during word recognition:
      evidence for callosal transfer dysfunction in dyslexic adults.
AB  - Participants report briefly-presented words more accurately when two copies are
      presented, one in the left visual field (LVF) and another in the right visual
      field (RVF), than when only a single copy is presented. This effect is known as
      the 'redundant bilateral advantage' and has been interpreted as evidence for
      interhemispheric cooperation. We investigated the redundant bilateral advantage
      in dyslexic adults and matched controls as a means of assessing communication
      between the hemispheres in dyslexia. Consistent with previous research, normal
      adult readers in Experiment 1 showed significantly higher accuracy on a word
      report task when identical word stimuli were presented bilaterally, compared to
      unilateral RVF or LVF presentation. Dyslexics, however, did not show the
      bilateral advantage. In Experiment 2, words were presented above fixation, below
      fixation or in both positions. In this experiment both dyslexics and controls
      benefited from the redundant presentation. Experiment 3 combined whole words in
      one visual field with word fragments in the other visual field (the initial and
      final letters separated by spaces). Controls showed a bilateral advantage but
      dyslexics did not. In Experiments 1 and 3, the dyslexics showed significantly
      lower accuracy for LVF trials than controls, but the groups did not differ for
      RVF trials. The findings suggest that dyslexics have a problem of
      interhemispheric integration and not a general problem of processing two lexical
      inputs simultaneously.

PMID- 17544496
TI  - Cross-link density evaluation through softening tests: effect of ethanol
      concentration.
AB  - OBJECTIVES: The aim of this study was to investigate whether the ethanol
      concentration used would influence the outcomes obtained through softening tests
      when comparing light-activation modes. METHODS: Disc specimens (n=20) of Filtek
      Z250 and Filtek Z100 (3M ESPE) were light activated by standard (S) and pulse
      delay (PD) modes. Initial Knoop hardness (KHN) measurements were performed 24h
      after dry storage at 37 degrees C. Half of the specimens (n=10) of each resin
      composite were stored in absolute ethanol (100%) and the other half in 75%
      ethanol solution, for 24h at room temperature, and KHN was determined anew.
      Initial hardness data were submitted to Student's t-test (p=0.05). Percentages of
      hardness decrease were analyzed by two-way ANOVA followed by pairwise Tukey's
      test (p=0.05). The statistical analyses were performed separately for each resin
      composite. RESULTS: No statistically significant differences were observed
      between standard and pulse-delay modes for initial Knoop hardness values. After
      storage in 75% ethanol solution, KHN was decreased in all cases but no
      significant differences were detected between light-activation modes (Filtek
      Z250: PD=12.6%, S=13.5%; Filtek Z100: PD=13.5%, S=11.8%) regardless of the resin
      composite tested. After absolute ethanol storage, higher decrease in KHN were
      observed. Samples light-activated by the PD mode (Filtek Z250=20.4% and Filtek
      Z100=16.9%) exhibited significantly higher percentage decrease of KHN than
      specimens light-activated by the standard mode (Filtek Z250=14.1% and Filtek
      Z100=8.8%), regardless of the resin-composite tested. CONCLUSION: The ethanol
      concentration affected the outcomes of the softening test.

PMID- 17544497
TI  - Preoperative chemotherapy in patients with resectable non-small cell lung cancer:
      results of the MRC LU22/NVALT 2/EORTC 08012 multicentre randomised trial and
      update of systematic review.
AB  - BACKGROUND: Although surgery offers the best chance of cure for patients with non
      small cell lung cancer (NSCLC), the overall 5-year survival rate is modest, and
      improvements are urgently needed. In the 1990s, much interest was generated from
      two small trials that reported striking results with neo-adjuvant chemotherapy,
      and therefore our intergroup randomised trial was designed to investigate
      whether, in patients with operable non-small cell lung cancer of any stage,
      outcomes could be improved by giving platinum-based chemotherapy before surgery.
      METHODS: Patients were randomised to receive either surgery alone (S), or three
      cycles of platinum-based chemotherapy followed by surgery (CT-S). Before
      randomisation, clinicians chose the chemotherapy that would be given from a list
      of six standard regimens. The primary outcome measure was overall survival, which
      was analysed on an intention-to-treat basis. This study is registered as an
      International Standard Randomised Controlled Trial, number ISRCTN25582437.
      RESULTS: 519 patients were randomised (S: 261, CT-S: 258) from 70 centres in the
      UK, Netherlands, Germany, and Belgium. Most (61%) were clinical stage I, with 31%
      stage II, and 7% stage III. Neo-adjuvant chemotherapy was feasible (75% of
      patients received all three cycles of chemotherapy), resulted in a good response
      rate (49% [95% CI 43%-55%]) and down-staging in 31% (25%-37%) of patients, and
      did not alter the type or completeness of the surgery (lobectomy: S: 56%, CT-S:
      60%, complete resection: S: 80%, CT-S: 82%). Post-operative complications were
      not increased in the CT-S group, and no impairment of quality of life was
      observed. However, there was no evidence of a benefit in terms of overall
      survival (hazard ratio [HR] 1.02, 95% CI 0.80-1.31, p=0.86). Updating the
      systematic review by addition of the present result suggests a 12% relative
      survival benefit with the addition of neoadjuvant chemotherapy (1507 patients, HR
      0.88, 95% CI 0.76-1.01, p=0.07), equivalent to an absolute improvement in
      survival of 5% at 5 years INTERPRETATION: Although there was no evidence of a
      difference in overall survival with neo-adjuvant chemotherapy, the result is
      statistically consistent with previous trials, and therefore adds considerable
      weight to the current evidence.

PMID- 17544498
TI  - Chemotherapy and surgery for operable NSCLC.

PMID- 17544499
TI  - Avidin-biotin binding-based cell seeding and perfusion culture of liver-derived
      cells in a porous scaffold with a three-dimensional interconnected flow-channel
      network.
AB  - To engineer implantable liver tissues, we designed a novel scaffold with a three
      dimensional (3D) branching and joining flow-channel network comprising multiple
      tetrahedral units (4-mm edge length). For the fabrication of this network,
      biodegradable polycaprolactone (PCL) and 80% (w/w) NaCl salt particles serving as
      porogen were thoroughly mixed and applied in a selective laser sintering (SLS)
      process, a technique adapted to rapid prototyping. We thus obtained a scaffold
      that had high (89%) porosity with a pore size of 100-200 microm and 3D flow
      channels. To evaluate its biocompatibility, human hepatoma Hep G2 cells were
      seeded into the scaffold using avidin-biotin (AB) binding and cultured in a
      perfusion system for 9 days. The results demonstrated that such 3D flow channels
      are essential to the cells' growth and function. In addition, the AB binding
      based seeding remarkably improved the overall performance of the cell-loaded
      scaffolds. The fabrication of a much finer scaffold, having a 500 cm(3) scale,
      based on the same design and the use of human hepatocyte progenitors, may, in the
      near future, lead to the development of an implantable liver tissue equivalent
      for use in humans.

PMID- 17544500
TI  - Silicon substitution in the calcium phosphate bioceramics.
AB  - Silicon (Si) substitution in the crystal structures of calcium phosphate (CaP)
      ceramics such as hydroxyapatite (HA) and tricalcium phosphate (TCP) generates
      materials with superior biological performance to stoichiometric counterparts.
      Si, an essential trace element required for healthy bone and connective tissues,
      influences the biological activity of CaP materials by modifying material
      properties and by direct effects on the physiological processes in skeletal
      tissue. The synthesis of Si substituted HA (Si-HA), Si substituted alpha-TCP (Si
      alpha-TCP), and multiphase systems are reviewed. The biological performance of
      these Si substituted CaP materials in comparison to stoichiometric counterparts
      is discussed. Si substitution promotes biological activity by the transformation
      of the material surface to a biologically equivalent apatite by increasing the
      solubility of the material, by generating a more electronegative surface and by
      creating a finer microstructure. When Si is included in the TCP structure,
      recrystallization to a carbonated HA is mediated by serum proteins and osteoblast
      like cells. Release of Si complexes to the extracellular media and the presence
      of Si at the material surface may induce additional dose-dependent stimulatory
      effects on cells of the bone and cartilage tissue systems.

PMID- 17544501
TI  - The role of ERK signaling in protein hydrogel remodeling by vascular smooth
      muscle cells.
AB  - Collagen type I and fibrin hydrogels have been used for cell-based therapies and
      tissue engineering. These matrices can be broken down and remodeled by cells, but
      the effects that these proteins have on cell function are not completely
      understood. We examined activation of the extracellular signal-regulated kinase
      (ERK) signaling pathway by vascular smooth muscle cells (VSMC) in response to 2D
      and 3D matrices of type I collagen, fibrin, or a 1:1 composite mixture of these
      proteins. After 3 days of culture, ERK phosphorylation, osteopontin secretion,
      and MMP-2 activation were all markedly increased in 3D matrices, compared with 2D
      substrates. A strong positive correlation existed between these protein markers
      of the synthetic phenotype and phosphorylated ERK levels, and this relationship
      persisted across matrix geometries and compositions. Cell proliferation in 3D
      matrices was inversely correlated to ERK activation, while on 2D substrates a
      modest positive correlation was observed. Pharmacologic inhibition of ERK
      signaling confirmed that this pathway was involved in the observed phenotype
      shifts. This study suggests that contextual activation of the ERK pathway results
      in different effects on cell phenotype, depending on the geometry and composition
      of the ECM. These findings add to our understanding of cell function and
      remodeling in protein-based hydrogel biomaterials.

PMID- 17544502
TI  - Adipose tissue engineering with naturally derived scaffolds and adipose-derived
      stem cells.
AB  - A tissue-engineered adipose substitute would have numerous applications in
      plastic and reconstructive surgery. This work involves the characterization of
      the in vitro cellular response of primary human adipose-derived stem cells (ASC)
      to three dimensional, naturally derived scaffolds. To establish a more thorough
      understanding of the influence of the scaffold environment on ASC, we have
      designed several different soft tissue scaffolds composed of decellularized human
      placenta and crosslinked hyaluronan (XLHA). The cellular organization within the
      scaffolds was characterized using confocal microscopy. Adipogenic differentiation
      was induced and the ASC response was characterized in terms of glycerol-3
      phosphate dehydrogenase (GPDH) activity and intracellular lipid accumulation. The
      results indicate that the scaffold environment impacts the ASC response and that
      the adipogenic differentiation of the ASC was augmented in the non-adhesive XLHA
      gels.

PMID- 17544503
TI  - Regulation of gene expression in mouse trophoblast cells by interferon-gamma.
AB  - We have previously shown that interferon-gamma (IFN-gamma) activates phagocytosis
      and induces nitric oxide production in cultured mouse trophoblast cells. In the
      present study we examined the effect of this cytokine on ectoplacental cone and
      gene expression in trophoblast cells. Ectoplacental cones were obtained during
      the postimplantation period on gestational day 7.5 from CD-1 mice and exposed to
      100U/mL IFN-gamma. Ectoplacental cone morphology, cell proliferation and death
      were also determined upon IFN-gamma treatment. Complementary DNA macroarray and
      semiquantitative RT-PCR were used to analyze gene expression. IFN-gamma treatment
      did not alter ectoplacental cone morphology, trophoblast cell proliferation or
      death. However, using gene array technology, we observed that IFN-gamma affected
      the developing trophoblast, altering the level of mRNA expression, which resulted
      in upregulation of 35 genes and downregulation of seven others. The upregulation
      of transcription factors and immune response-associated genes suggests that IFN
      gamma is involved in processes beyond immunological homeostasis and plays an
      important role in placental development and function.

PMID- 17544504
TI  - Maintenance therapy with imatinib appears necessary despite molecular remission
      in FIP1L1-PDGFRA fusion gene positive hypereosinophilic disorder.
AB  - Patients with primary hypereosinophilic disorders who are positive for the FIP1L1
      PDGFRA fusion gene mutation are highly responsive to therapy with imatinib
      mesylate. A 35-year-old man with FIP1L1-PDGFRA positive hypereosinophilic
      syndrome and cardiac involvement, was treated with imatinib 100 mg daily.
      Hematologic and molecular remission and reversal of end-organ damage was
      achieved. He was then lost to follow up for 19 months. Imatinib successfully
      reinduced hematologic and molecular remission but worsening cardiac involvement
      was not reversed. Our experience and a review of limited literature suggest that
      imatinib maintenance therapy is necessary despite molecular remission of the
      FIP1L1-PDGFRA mutation.

PMID- 17544505
TI  - Distinct clonal origins of systemic mastocytosis and associated B-cell lymphoma.
AB  - Systemic mastocytosis (SM) may rarely be associated with lymphoproliferative
      disorders. In such cases, the relationship between the neoplastic mast cells and
      the malignant lymphocytes remains unclear. We describe a patient with indolent SM
      whose bone marrow showed evidence of low-grade B-cell lymphoma. By detecting the
      activating KIT mutation D816V in the microdissected bone marrow mast cells, but
      not in the neoplastic B-lymphocytes, we demonstrate the distinct clonal origins
      of the mastocytosis and lymphoma when these two entities coexist. We also
      highlight the clinical and pathologic differences between SM associated with
      lymphoid as opposed to myeloid neoplasms and discuss their pathogenesis.

PMID- 17544506
TI  - Thalidomide-induced partial stable remission in a case of refractory progressive
      B Cell Chronic Lymphoid Leukemia.

PMID- 17544507
TI  - Monomeric red fluorescent protein as a reporter for macromolecular localization
      in Streptomyces coelicolor.
AB  - The enhanced green fluorescent protein (eGFP) is widely used to investigate cell
      type specific gene expression and protein localization in the filamentous
      streptomycetes. To broaden the scope of cell biological investigation in these
      organisms, we have adapted shuttle vectors for the construction of gene fusions
      to the monomeric red fluorescent protein (mRFP1) and have tested them in
      Streptomyces coelicolor. Using fusions of mRFP1 to the cell division proteins
      DivIVA and FtsZ, we show that mRFP1 is comparable to eGFP for cell biological
      research in this organism and suggest that this paves the way for the future use
      of two-color imaging and FRET.

PMID- 17544508
TI  - Comparison of growth phase on Salmonella enterica serovar Typhimurium invasion in
      an epithelial cell line (IPEC J2) and mucosal explants from porcine small
      intestine.
AB  - Salmonella Typhimurium DT104 is a zoonotic enteropathogen of increasing concern
      for human health. In this study, the influence of growth phase on invasiveness of
      a S. Typhimurium DT104 field isolate and two reference strains (SL1344 and ATCC
      14028) was compared in IPEC J2 cells and mucosal explants from porcine ileum.
      Internalized bacteria were quantified by a gentamicin resistance assay. After 90
      min of exposure to the apical aspect of epithelial monolayers or luminal surface
      of explants, internalization of all S. Typhimurium strains in mid-logarithmic
      phase of bacterial growth was comparable. Internalization of stationary phase
      bacteria was reduced relative to log phase bacteria, with DT104 exhibiting the
      greatest decrease. Growth phase-related differences in S. Typhimurium invasion
      are similar in porcine intestinal epithelial cells and mucosal explants, but may
      be greater in multidrug-resistant strains.

PMID- 17544509
TI  - The dependence of spinal cord development on corticospinal input and its
      significance in understanding and treating spastic cerebral palsy.
AB  - The final phase of spinal cord development follows the arrival of descending
      pathways which brings about a reorganisation that allows mature motor behaviours
      to emerge under the control of higher brain centres. Observations made during
      typical human development have shown that low threshold stretch reflexes,
      including excitatory reflexes between agonist and antagonist muscle pairs are a
      feature of the newborn. However, perinatal lesions of the corticospinal tract can
      lead to abnormal development of spinal reflexes that includes retention and
      reinforcement of developmental features that do not emerge in adult stroke
      victims, even though they also suffer from spasticity. This review describes
      investigations in animal models into how corticospinal input may drive segmental
      maturation. It compares their findings with observations made in humans and
      discusses how therapeutic interventions in cerebral palsy might aim to correct
      imbalances between descending and segmental inputs, bearing in mind that
      descending activity may play the crucial role in development.

PMID- 17544510
TI  - Variants in the promoter region of IKBL/NFKBIL1 gene may mark susceptibility to
      the development of chronic Chagas' cardiomyopathy among Trypanosoma cruzi
      infected individuals.
AB  - Chagas' disease, caused by Trypanosoma cruzi, is an inflammatory disorder leading
      to chronic Chagas cardiomyopathy (CCC). Only one third of T. cruzi-infected
      individuals progress to CCC while the others are considered asymptomatic (ASY).
      The human inhibitory kappaB-like gene (IKBL/NFKBIL1), homologous to the IkappaB
      family of proteins that regulate the NFkappaB family of transcription factors, is
      suggested as a putative inhibitor of NFkappaB. We investigated two functional
      polymorphisms, -62A/T and -262A/G, in the promoter of IKBL by PCR-RFLP analysis
      in 169 patients with CCC and 76 ASY. Genotype distributions for both -62A/T and 
      262A/G differed between the CCC and ASY (chi2=7.3; P=0.025 and chi2=6.8; P=0.03,
      respectively). Subjects, homozygous for the -62A allele, had three-fold risk of
      developing CCC compared with those carrying the TT genotype (P=0.0095; Odds Ratio
      [OR]=2.9; [95% CI 1.2-7.3]). Similar trend was observed for the -262A homozygotes
      (P=0.005; OR=2.7 [95% CI 1.3-6.0]. The haplotype -262A -62A was prevalent in
      patients with CCC (40% versus 24%; OR 2.1 [95% CI 1.4-3.3]; Pc=0.0014). The IKBL
      locus itself or another critical gene in this region may confer susceptibility to
      the development of CCC.

PMID- 17544511
TI  - Biomechanical assessment of radial optic neurotomy.
AB  - PURPOSE: A biomechanical model was constructed to simulate the potential
      therapeutic effect that the surgical procedure radial optic neurotomy (RON) would
      have on an eye with a central retinal vein occlusion. DESIGN: Experimental study.
      CONTROLS: Model eyes undergoing RON were compared to control eyes under the same
      baseline conditions. INTERVENTION: Radial optic neurotomy. We modeled the optic
      nerve, lamina cribrosa, and the sclera separately and then reassembled the
      components. Material properties of the sclera and lamina cribrosa were extracted
      from the literature and both stiff and more elastic values were used for the
      optic nerve. Intraocular and arterial pressures were varied across a wide range
      in the analysis. MAIN OUTCOME MEASURE: Change in central retinal vein lumen size.
      RESULTS: Over a clinically relevant range of boundary conditions, the increase in
      the lumen area of the central retinal vein lumen after RON remained trivial,
      ranging from 1% to a maximum of 5%. CONCLUSIONS: The biomechanical effect of RON
      is negligible, and is unlikely to be a procedure that could mechanically
      ameliorate the clinical sequelae of a central vein occlusion.

PMID- 17544512
TI  - The effect of ancillary ligand chirality and phenanthroline functional group
      substitution on the cytotoxicity of platinum(II)-based metallointercalators.
AB  - Fifteen platinum(II)-based metallointercalators have been synthesised that
      utilise substituted 1,10-phenanthroline (phen) ligands, including 5-chloro-1,10
      phenanthroline (5-Cl-phen), 5-methyl-1,10-phenanthroline (5-CH3-phen), 5-amino
      1,10-phenanthroline (5-NH2-phen), 5-nitro-1,10-phenanthroline (5-NO2-phen) and
      dipyrido[3,2-d:2',3'-f]quinoxaline (dpq), and achiral ethylenediamine (en) and
      the chiral ancillary ligands 1S,2S-diaminocyclohexane (S,S-dach) and 1R,2R
      diaminocyclohexane (R,R-dach). Their cytotoxicity in the L1210 murine leukaemia
      cell line was determined using growth inhibition assays. The most cytotoxic metal
      complexes are those that contain S,S-dach ancillary ligands and 5-CH3-phen
      intercalating ligands. One metallointercalator [Pt(5-CH3-phen)(S,S-dach)]Cl2
      (5MESS), displays a 5-10-fold increase in cytotoxicity compared to the clinical
      agent cisplatin. From DNA binding experiments there appears to be no significant
      difference between any of the metal complexes, indicating that neither DNA
      binding affinity nor the mode of binding/DNA adduct formed is the sole
      determinant of the cytotoxicity of this family of platinum(II)-based
      metallointercalators.

PMID- 17544513
TI  - Reduction of dehydroascorbic acid at low pH.
AB  - Ascorbic acid and dehydroascorbic acid are unstable in aqueous solution in the
      presence of copper and iron ions, causing problems in the routine analysis of
      vitamin C. Their stability can be improved by lowering the pH below 2, preferably
      with metaphosphoric acid. Dehydroascorbic acid, an oxidised form of vitamin C,
      gives a relatively low response on the majority of chromatographic detectors, and
      is therefore routinely determined as the increase of ascorbic acid formed after
      reduction. The reduction step is routinely performed at a pH that is suboptimal
      for the stability of both forms. In this paper, the reduction of dehydroascorbic
      acid with tris-[2-carboxyethyl] phosphine (TCEP) at pH below 2 is evaluated.
      Dehydroascorbic acid is fully reduced with TCEP in metaphosphoric acid in less
      than 20 min, and yields of ascorbic acid are the same as at higher pH. TCEP and
      ascorbic acid formed by reduction, are more stable in metaphosphoric acid than in
      acetate or citrate buffers at pH 5, in the presence of redox active copper ions.
      The simple experimental procedure and low probability of artefacts are major
      benefits of this method, over those currently applied in a routine assay of
      vitamin C, performed on large number of samples.

PMID- 17544514
TI  - Absence of an association of tumor necrosis factor (TNF)-alpha G308A, interleukin
      6 (IL-6) G174C and interleukin-10 (IL-10) G1082A polymorphism in women with
      preeclampsia.
AB  - OBJECTIVE: TNF-alpha G308A, IL-6 G174C and IL-10 G1082A polymorphisms have
      recently been associated with preeclampsia (PE). The aim of this study was to
      clarify whether the occurrence of TNF-alpha, IL-6 and IL-10 polymorphisms is
      increased in women of our population with PE in a previous pregnancy. METHODS: A
      retrospective, controlled, open, multicenter study was carried out in 107 women
      with a history of PE and 107 women with uncomplicated pregnancies. Smears from
      buccal gingival cells were analyzed for the polymorphisms of TNF-alpha, IL-6 and
      IL-10 by hybridization on microarrays. Statistical significance was calculated by
      the chi-quadrant test. RESULTS: Heterozygocity for the gene polymorphisms did not
      occur more often in preeclamptic women compared with controls (TNF-alpha: 29.0%
      versus 24.3%, p>0.05; IL-6: 46.7% versus 51.4%, p>0.05; or IL-10: 49.5% in each).
      Moreover, there was no significant difference between preeclamptics and controls
      with regard to homozygocity for TNF alpha (1.9% versus 3.7%, p>0.05); IL-6 (17.8%
      versus 13.1%, p>0.05); and IL-10 (30.8% versus 32.7%, p>0.05). CONCLUSION: In
      contrast to the findings of some other investigators, gene polymorphisms do not
      seem to be important in our population for development of PE.

PMID- 17544515
TI  - Antecedents, concomitants and consequences of anger attacks in depression.
AB  - Anger attacks are episodes of intense anger with autonomic arousal, which occur
      in response to often trivial provocations. This study explores some of the
      antecedents, concomitants, and consequences of anger attacks in patients with
      depression. The sample comprised three groups: depression with anger attacks
      (n=20), depression without anger attacks (n=20) and normal controls (n=20).
      Subjects were administered the Mini International Neuropsychiatric Interview, the
      Anger Attack Questionnaire, Irritability, the Depression Anxiety Scale, the State
      Trait Anger Expression Inventory, the Psychoticism Extraversion Neuroticism
      Inventory, the Hassles Scale, the World Health Organization Quality of Life-BREF
      Version and the Dysfunctional Analysis Questionnaire. Depressed patients with
      anger attacks exhibited more suicide-related phenomena and dysfunction scores in
      comparison to depressed patients without anger attacks. Depressed patients with
      anger attacks also had higher scores of anxiety, irritability, trait-anger, anger
      out, anger expression, psychoticism, hassles, and poor quality of life in
      comparison to the other two groups. In conclusion, anger attacks adversely affect
      the lives of depressed patients and their family members and may serve as a
      qualifier for partially distinct syndrome of depression.

PMID- 17544516
TI  - Simple methods for measurement of bovine mucosal antibody responses in vivo.
AB  - The mucosal immune response serves as the first line of defence against many
      bacterial and viral diseases. Therefore, measurement of mucosal immune responses
      is important in evaluating mucosal immunisation protocols and understanding
      initial host/pathogen interactions. In this study we compare two methods for
      repeated sampling of bovine rectal mucosal secretions, namely rectal swabbing and
      rectal biopsies, and evaluate a simple swabbing method for sampling bovine nasal
      secretions. Both rectal swabs and rectal biopsies yielded similar quantities of
      total IgA (TIgA)/ml. However, rectal biopsies yielded five times more total IgG
      (TIgG)/ml than rectal swabs. Blood contamination was estimated to contribute
      approximately 7% of TIgG and <0.05% TIgA in rectal swab samples compared to 40%
      of TIgG and 4.5% of TIgA in rectal biopsy samples, indicating that rectal
      swabbing was more effective at sampling rectal mucosal secretions. Nasal swabs
      were effective at obtaining nasal secretion samples with only 1% of TIgG and
      <0.05% TIgA estimated to be blood derived. Furthermore, H7 flagellin-specific
      antibodies were detected in both nasal and rectal swab samples following either
      rectal immunisation with purified H7 flagellin or oral challenge with live E.
      coli O157:H7, indicating that both techniques are effective methods for
      monitoring mucosal antibody responses in cattle.

PMID- 17544517
TI  - Effects of adenotonsillectomy on speech spectrum in children.
AB  - OBJECTIVE: The vocal tract, which starts from the glottis and extends to the lips
      is considered to be a resonator for speech production. Enlarged palatine tonsils
      may cause hypernasal speech, oral breathing or muffled voice. Changes in the
      structure of this resonator are assumed to modify the speech characteristics. The
      aim of this study was to evaluate changes in acoustic feature of speech after
      adenotonsillectomy in children and to establish concepts of management and
      rational therapeutic approach. METHODS: Before and after surgery, an acoustic
      analysis was made to 40 children, aged between 5 and 14 years old, with enlarged
      palatine tonsils and hypetrophic adenoids. Phonetically balanced sentences were
      carried out and digitalized with Multi Dimensional Voice Program (MDVP, Kay
      Elemetrics). As a control group, 40 healthy children were identified. These
      parameters were estimated: average of fundamental frequency (Fo), Jitt, Shim,
      noise to harmonics ratio (NHR), voice turbulence index (VTI), soft phonation
      index (SPI), degree of voiceless (DUV) and degree of voice breaks (DVB). RESULTS:
      After adenotonsillectomy, our data showed an improvement in all the parameters:
      the analysis of Fo, Jitt, Shim, NHR, VTI, SPI, DUV and DVB showed a postoperative
      decrease; comparison with healthy children highlighted a postoperative
      normalization of NHR, VTI and DVB. CONCLUSIONS: The postoperative improvement of
      the parameters suggests a reduction of the nasal resonance and the improvement of
      voice quality. MDVP method may be useful for analyzing speech characteristics,
      evaluating the effects of surgical excision and therapeutic approach: in selected
      cases of patients with enlarged tonsils, the decision to perform tonsillectomy
      depends on its potential positive effect on speech too.

PMID- 17544518
TI  - The effect of caffeic acid phenethyl ester on the prevention of experimentally
      induced myringosclerosis.
AB  - OBJECTIVES: Myringosclerosis is a common sequela of ventilation tube insertion
      for the treatment of the otitis media with effusion. Several antioxidants have
      been identified to prevent myringosclerosis. The objective of this study was to
      investigate the effect of caffeic acid phenethyl ester (CAPE) on the prevention
      of experimentally induced myringosclerosis. METHODS: Thirty-five Sprague-Dawley
      rats were unilaterally myringotomized. The rats were divided into four groups
      randomly: group 1 received no treatment, group 2 received intraperitoneally
      administered saline and group 3 received intraperitoneally administered CAPE. The
      tympanic membranes were examined by otomicroscopy on the 15th day after
      treatment. The membranes were then harvested and evaluated histologically by
      light microscopy. RESULTS: The tympanic membranes from group 1 showed extensive
      myringosclerosis; those from group 2 showed a similar occurrence of
      myringosclerosis. However, group 3 had a reduced occurrence of myringosclerosis
      by otomicroscopic evaluation. Under light microscopic examination, the lamina
      propria of the pars tensa was found to be thicker and more sclerotic in groups 1
      and 2 when compared with group 3. CONCLUSIONS: Systemic treatment with CAPE was
      found to be effective in the prevention of sclerotic lesions in myringotomized
      rat tympanic membranes.

PMID- 17544519
TI  - Thalamic synchrony and dynamic regulation of global forebrain oscillations.
AB  - The circuitry within the thalamus creates an intrinsic oscillatory unit whose
      function depends critically on reciprocal synaptic connectivity between
      excitatory thalamocortical relay neurons and inhibitory thalamic reticular
      neurons along with a robust post-inhibitory rebound mechanism in relay neurons.
      Feedforward and feedback connections between cortex and thalamus reinforce the
      thalamic oscillatory activity into larger thalamocortical networks to generate
      sleep spindles and spike-wave discharge of generalized absence epilepsy. The
      degree of synchrony within the thalamic network seems to be crucial in
      determining whether normal (spindle) or pathological (spike-wave) oscillations
      occur, and recent studies show that regulation of excitability in the reticular
      nucleus leads to dynamical modulation of the state of the thalamic circuit and
      provide a basis for explaining how a variety of unrelated genetic alterations
      might lead to the spike-wave phenotype. In addition, given the central role of
      the reticular nucleus in generating spike-wave discharge, these studies have
      suggested specific interventions that would prevent seizures while still allowing
      normal spindle generation to occur. This review is part of the INMED/TINS special
      issue Physiogenic and pathogenic oscillations: the beauty and the beast, based on
      presentations at the annual INMED/TINS symposium (http://inmednet.com).

PMID- 17544520
TI  - Effect of chromatin upon Agrobacterium T-DNA integration and transgene
      expression.
AB  - Agrobacterium tumefaciens transfers DNA (T-DNA) to plant cells, where it
      integrates into the plant genome. Little is known about how T-DNA chooses sites
      within the plant chromosome for integration. Previous studies indicated that T
      DNA preferentially integrates into transcriptionally active regions of the
      genome, especially in 5'-promoter regions. This would make sense, considering
      that chromatin structure surrounding active promoters may be more "open" and
      accessible to foreign DNA. However, recent results suggest that this seemingly
      non-random pattern of integration may be an artifact of selection bias, and that
      T-DNA may integrate more randomly than previously thought. In this chapter, I
      discuss the history of these observations and the role chromatin proteins may
      play in T-DNA integration and transgene expression. Understanding how chromatin
      conformation may influence T-DNA integration will be important in developing
      strategies for reproducible and stable transgene expression, and for gene
      targeting.

PMID- 17544522
TI  - Targeted disruption of the murine large nuclear KIAA1440/Ints1 protein causes
      growth arrest in early blastocyst stage embryos and eventual apoptotic cell
      death.
AB  - The KIAA1440 protein contains no significant domains that allow for a prediction
      of its function, despite the fact that it is an extremely large protein
      comprising 2222 amino acids. In our current study, we show that the developing
      KIAA1440(-/-) mouse embryo in a pure ICR background arrests its growth at the
      early blastocyst stage, whereas the majority of the KIAA1440(-/-) embryos of
      mixed genetic backgrounds do not progress beyond the morula stage, approximately
      0.5 days earlier. KIAA1440(-/-) embryos exhibited no abnormal localization of E
      cadherin or beta-catenin and no obvious compaction abnormalities at the morula
      stage. In addition, E3.5 KIAA1440(-/-) embryos are not viable even in in vitro
      cultures. Both TUNEL and FAM-caspase-3/7 assays performed on these embryos
      consistently showed that E3.5 KIAA1440(-/-) embryos had activated caspase-3/7,
      which then induced an apoptotic response predominantly within the inner cell mass
      of the blastocyst. Moreover, qRT-PCR analysis showed that KIAA1440(-/-) embryos
      had increased levels of the unprocessed, primary U2 snRNA transcript but
      decreased levels of the mature U2 snRNA transcript compared to heterozygotes. The
      impaired processing of U2 snRNA and the predominantly nuclear localization of
      KIAA1440 protein is also very consistent with recently reported data showing that
      it is the largest subunit of the integrator complex, which mediates U1 and U2
      snRNA 3'-end processing. Large nuclear KIAA1440/Ints1 is thus suggested to play
      non-redundant roles in the cell such as the formation of a scaffold for the
      assembly of the integrator complex.

PMID- 17544521
TI  - The localization of nuclear exporters of the importin-beta family is regulated by
      Snf1 kinase, nutrient supply and stress.
AB  - In the budding yeast Saccharomyces cerevisiae, four members of the importin-beta
      family of nuclear carriers, Xpo1p/Crm1p, Cse1p, Msn5p and Los1p, function as
      exporters of protein and tRNA. Under normal growth conditions GFP-tagged
      exporters are predominantly associated with nuclei. The presence of Snf1 kinase,
      a key regulator of cell growth and a metabolic sensor, controls the localization
      of GFP-exporters. Additional glucose-dependent, but Snf1-independent, mechanisms
      regulate carrier distribution and a switch from fermentable to non-fermentable
      carbon sources relocates all of the carriers, suggesting a link to the
      nutritional status of the cell. Moreover, stress controls the proper localization
      of GFP-exporters, which mislocalize upon exposure to heat, ethanol and
      starvation. Stress may activate the MAPK cell integrity cascade, and we tested
      the role of this pathway in exporter localization. Under non-stress conditions,
      the proper distribution of GFP-Cse1p and Xpo1p/Crm1p-GFP requires kinases of the
      cell integrity cascade. By contrast, Msn5p-GFP and Los1p-GFP rely on the MAPK
      module to relocate to the cytoplasm when cells are stressed with ethanol. Our
      results indicate that the association of nuclear exporters with nuclei is
      controlled by multiple mechanisms that are organized in a hierarchical fashion
      and linked to the physiological state of the cell.

PMID- 17544523
TI  - Insulin-resistance (IR) in older age.
AB  - A study pool of 1549 normoglycemic elderly in the age range of 65-84 years, taken
      from the epidemiological Italian Longitudinal Study on Aging (ILSA), was
      constructed. The values of IR, %B and %S were analyzed using the homeostasis
      assessment model-2 (HOMA-2). In the subjects displaying normal values of several
      studied parameters such as the arterial blood pressure, total cholesterol (T-CH),
      high-density lipoproteins (HDL), and triglycerides (TG), the values of IR, %B and
      %S remained in the normal ranges (in average 1.66+/-1.11, 133.64+/-63.56 and
      91.12+/-79.75, respectively). These latter values increase in the subjects who
      had altered values of the studied basic parameters listed above, and the
      increases were higher with the higher frequency of the altered parameters. The
      results seem to confirm the possibility that the normoglycemic elderly subjects
      having a compensatory insulin hypersecretion against the IR, may develop a type 2
      diabetes or a metabolic syndrome.

PMID- 17544524
TI  - Physical performance and creative activities of centenarians.
AB  - The human functional autonomy is reduced progressively with advancing age,
      although a considerable proportion of the centenarians maintain a good level of
      autosufficiency for the basic performance of the everyday life. Even if males
      have a lower probability to reach the centenarian age than females do, the male
      centenarians display generally better functional conditions than the females.
      Actually, there are no systemic studies on centenarian works or activities;
      nevertheless, the examples of several representative persons (artists,
      scientists, explorers, etc.) who remained active even after this age indicate
      that such a possibility is realistic, and that the maintenance of vital interest
      and passions, thus preserving competence and professional attitudes, is not in
      conflict with the reaching of extreme longevity.

PMID- 17544525
TI  - N-terminal pro-B-type natriuretic peptide as a predictor of repeat coronary
      revascularization.
AB  - BACKGROUND: Recent studies suggest that natriuretic peptides are potential
      biomarkers for myocardial ischemia. However, little is known about the value of
      NT-proBNP as a predictor of repeat revascularization (RR) at follow-up
      angiography in patients with normal LV systolic function. METHODS: We collected
      and analyzed the clinical and angiographic data from 445 consecutive patients
      (62.5+/-10.1 years; 73% males) who showed normal LV systolic function and no
      regional wall motion abnormalities on transthoracic echocardiogram performed at
      baseline and follow-up angiography. RESULTS: Overall, NT-proBNP level on
      admission for follow-up angiography was significantly higher in patients with RR
      (n=55) than those without RR (n=390) [92.4 (47.5-178.5) pg/ml vs. 54.8 (30.6
      93.1) pg/ml, P<0.001]. In asymptomatic patients, NT-proBNP did not show
      significant difference between patients with RR and those without RR (P=0.42). An
      elevated NT-proBNP level, especially in symptomatic patients (n=77) (>87.5 pg/ml
      as an optimal cut off value) was a strong independent predictor for RR at follow
      up angiography (OR, 12.3; 95% CI, 3.25-46.2; P=0.001). NT-proBNP (>122.9 pg/ml)
      showed high specificity (85.9%) and negative predictive value (91.0%) for
      predicting RR in overall patients. However, NT-proBNP (>97.0 pg/ml) showed low
      sensitivity (49.1%) and positive predictive value (23.5%). The areas under the
      receiver operator characteristic (ROC) curve in predicting RR in overall patients
      and symptomatic patients were 0.648 (95% CI; 0.564-0.732, P<0.001) and 0.768 (95%
      CI; 0.653-0.884, P<0.001), respectively. CONCLUSION: Our data show that NT-proBNP
      level at follow-up is a strong independent predictor for RR especially in
      symptomatic patients. Although routine measurement may be not useful for predict
      RR, NT-proBNP may help to identify patients with low risk of repeat
      revascularization.

PMID- 17544526
TI  - Comments on the article by Abboud et al. "Peripartum cardiomyopathy: a
      comprehensive review": a tribute to: A.B. Benchimol and P. Schlesinger.
AB  - Peripartum (or postpartum) cardiomyopathy is a rare disease affecting 1:1,500 to
      1:15,000 successful pregnancies in otherwise healthy women, has usually a
      relentless course and roughly 35% six-months mortality rate. In Latin America,
      Prof. A.B. Benchimol, the first Chairperson of Cardiology in the history of
      medical school in Brazil, and his North American colleague, Prof. Paulo
      Schlesinger, significantly contributed to the study of peripartum cardiomyopathy
      in Latin America and a remark must be made to their memory.

PMID- 17544527
TI  - Oral anticoagulants and fracture risk: clinical perspectives.

PMID- 17544528
TI  - Coronary stenting versus balloon angioplasty for acute myocardial infarction: a
      meta-regression analysis of randomized trials.
AB  - INTRODUCTION: Although stenting has been shown to reduce the need for target
      vessel revascularization (TVR) in acute myocardial infarction (AMI), the benefits
      in terms of mortality and reinfarction are still unclear. Previous meta-analyses
      have failed to include all currently available randomized trials. The aim of the
      current study was to perform an updated meta-analysis to evaluate the benefits of
      coronary stenting for AMI in terms of mortality, reinfarction, and TVR, and
      whether these benefits correlated with the patient's risk profile. METHODS: The
      literature was scanned by formal searches of electronic databases (MEDLINE and
      CENTRAL) from January 1990 to September 2006. We examined all completed,
      published, randomized trials of coronary stenting for AMI. The following key
      words were used for study selection: randomized trial, myocardial infarction,
      reperfusion, primary angioplasty, rescue angioplasty, stenting, and balloon
      angioplasty. Information on study design, type of stent, inclusion and exclusion
      criteria, primary endpoint, number of patients, angiographic and clinical
      outcome, were extracted by two investigators. Disagreements were resolved by
      consensus. RESULTS: A total of 13 randomized trials were identified and analyzed
      involving 6922 patients (3460 or 50% randomized to stent and 3462 or 50% to
      balloon). Stenting was not associated with a significant reduction in 30-day
      (2.9% versus 3.0%, p=0.81) and 1-year mortality (5.1% versus 5.2%, p=0.81), as
      compared to balloon angioplasty. However, a significant relationship was observed
      between patient's risk profile and mortality benefits from coronary stenting at
      30-day (beta -0.63 [-25.4; -2.45], p=0.022) and 1-year follow-up (beta -0.61 [
      15.9; -0.76], p=0.034). Stenting was associated with benefits in terms of TVR at
      both 30-day (3.1% versus 5.1%, p<0.0001) and 6 to 12 months (11.3% versus 18.4%,
      p<0.0001) follow-up, without any difference in terms of reinfarction.
      CONCLUSIONS: Among AMI patients undergoing primary angioplasty, coronary stent
      implantation, when anatomically and technically feasible, may be considered, in
      addition to benefits in terms of TVR, to reduce mortality in high-risk patients,
      who may be identified by the use of validated risk scores.

PMID- 17544529
TI  - Postmortem molecular analysis of KCNQ1 and SCN5A genes in sudden unexplained
      death in young Australians.
AB  - The cause of sudden death in young people remains unknown in up to 50% of
      postmortem cases. Mutations in the ion channel genes are known to cause primary
      arrhythmogenic disorders such as long QT and Brugada syndromes, which can present
      with sudden cardiac death and a negative autopsy. In this study, 59 sudden
      unexplained deaths occurring in Australians aged </=35 years with a negative
      autopsy, from 1994-2002, were studied. Genomic DNA was extracted from paraffin
      embedded tissues. Genetic analysis of the KCNQ1 and SCN5A genes was performed
      using denaturing high-performance liquid chromatography and direct DNA
      sequencing. Nine DNA sequence variants were identified in the KCNQ1 gene and 9
      sequence variants were identified in the SCN5A gene. In total, 23 out of 59 cases
      were found to have at least one DNA variant in KCNQ1 or SCN5A, of which one,
      H558R in the SCN5A gene, caused an amino acid substitution. None of the DNA
      variants were determined to be disease causing as they were also identified in
      control populations. In conclusion, no disease-causing mutations were found in
      the KCNQ1 or SCN5A genes in this cohort. A more selective screening approach,
      including only individuals with a clinical or family history of arrhythmogenic
      disorders, may yield greater success in identifying disease-causing mutations in
      cohorts of young individuals who have died suddenly.

PMID- 17544530
TI  - The Venture-balloon crush technique to treat a severely angulated bifurcation
      lesion via the radial approach--lessons learned.
AB  - We present the first described use of the Venture (St. Jude Medical Inc.)
      catheter to accomplish balloon crush stenting of a severely angulated bifurcation
      via the radial approach. We outline the lessons learned and pitfalls of
      performing percutaneous intervention to severely angulated bifurcations such as
      this one.

PMID- 17544531
TI  - Abnormal troponin I levels during pregnancy without acute coronary syndrome and
      without hypertensive disorders.

PMID- 17544532
TI  - Reliable and sensitive analysis of amino acids in the peptidoglycan of
      actinomycetes using the advanced Marfey's method.
AB  - For the chemotaxonomic classification of actinomycetes, we developed a new method
      for the detection of the 2, 6-diaminopimelic acid (A(2)pm) stereoisomers and 3
      hydroxy diaminopimelic acid (3-OH A(2)pm) in the cell wall peptidoglycan of
      actinomycetes using "the advanced Marfey's method", which consists of a
      chromatographic technique for the separation of amino acids into each of its
      enantiomers by derivatization with 1-fluoro-2, 4-dinitrophenyl-5-L-luecinamide (L
      FDLA) and D-FDLA, and a detection method using liquid chromatography/mass
      spectrometry (LC/MS). This method was successfully applied to determine the
      absolute configuration of the A(2)pm and detect the 3-OH A(2)pm included in the
      cell wall peptidoglycan of the standard strains. Because the procedure can be
      performed with very small amounts of an amino acid, it was possible to use one
      colony from an agar plate of the actinomycetes for the acid hydrolysis. In
      addition, the constituent amino acids and their absolute configurations in the
      cell wall of the actinomycetes could be simultaneously determined. Thus, a
      reliable, sensitive and rapid analytical method for amino acids including A(2)pm
      in the peptidoglycan of the microorganisms was established.

PMID- 17544534
TI  - Anger and fear: Separable effects of emotion and motivational direction on
      somatovisceral responses.
AB  - We studied whether emotion (anger vs. fear) and motivational direction (approach
      vs. withdrawal) have specific, separable, and independent somatovisceral response
      patterns. Imagination scripts about soccer game episodes with crossed Emotion x
      Motivational Direction content resulting in four experimental groups were
      presented to a total of N = 118 active soccer players. Self-reports reflected the
      emotion but not the motivational direction induction. Univariate and multivariate
      analyses of 24 somatovisceral variables and 2 a priori defined summary variables
      showed that anger and fear had specific response profiles with effect sizes
      correlating r = 0.53 with the respective effect sizes from a previous study.
      Approach and withdrawal profiles varied only in intensity. Emotion and
      motivational direction did not interact and had independent somatovisceral
      effects. Results suggest that anger and fear have separate underlying
      neurobiological organizations each capable of bi-directional motivational tuning
      of efferent pathways. Results support the Component Model of Somatovisceral
      Response Organization.

PMID- 17544533
TI  - Anger and psychobiological changes during smoking abstinence and in response to
      acute stress: prediction of smoking relapse.
AB  - Nicotine may be used to manage negative emotions, and recent research suggests
      that smokers with high levels of hostility may use cigarettes to cope with anger
      provoking situations. This study evaluated the extent to which a high level of
      trait anger is associated with risk for relapse among smokers interested in
      cessation. Chronic smokers with different levels of trait anger provided reports
      of withdrawal symptoms, craving, and state anger, and collected saliva samples
      for cortisol during 24-hour ad libitum smoking and the first 24-hour abstinence
      period of a quit attempt. They also attended a laboratory session conducted after
      the 24-hour abstinence during which they performed brief mental and social stress
      challenges and provided blood samples for adrenocorticotropin (ACTH) and cortisol
      assays. High trait anger was associated with greater increases in state anger,
      withdrawal symptoms, and craving during the first 24 h of abstinence. It was also
      associated with greater ACTH concentrations during the laboratory session. High
      trait anger was also associated with increased risk for early relapse. The
      findings support the hypothesis that smokers high in anger trait may have greater
      mood difficulties during abstinence and may be more vulnerable to early relapse
      than smokers with low anger trait.

PMID- 17544535
TI  - Production of a Rhizopus oryzae lipase from Pichia pastoris using alternative
      operational strategies.
AB  - Different cultivation strategies have been compared for the production of
      Rhizopus oryzae lipase (ROL) from Pichia pastoris. Several drawbacks have been
      found using a methanol non-limited fed-batch. On the one hand, oxygen limitation
      appeared at early cell dry weights and, on the other hand, high cell death was
      observed. A temperature limited fed-batch has been proposed to solve both
      problems. However, in our case study a methanol non-limited fed-batch results in
      better productivities. Finally, a lower salt medium were used to overcome cell
      death problems and a temperature limited fed-batch was applied thereafter to
      solve oxygen transfer limitations. This combined strategy has resulted in lower
      productivities when compared to a methanol non-limited fed-batch. However the
      culture could be longer prolonged and a 1.3-fold purer final product was obtained
      mainly due to cell death reduction.

PMID- 17544536
TI  - Identification of proteins from feeder conditioned medium that support human
      embryonic stem cells.
AB  - The maintenance of undifferentiated human embryonic stem cells (hESC) requires
      feeder cells, either in co-culture or feeder-free with conditioned medium (CM)
      from the feeders. In this study, we compared the CM of a supporting primary mouse
      embryonic feeder (MEF) and an isogenic but non-supporting MEF line (DeltaE-MEF)
      in order to gain an insight to the differential expression profile of secreted
      factors. Using two-dimensional electrophoresis (2-DE) and matrix-assisted laser
      desorption/ionization-time of flight (MALDI) tandem mass spectrometry, 13 protein
      identities were found to be downregulated in DeltaE-MEF compared to MEF, of which
      4 were found to be soluble factors and 3 proteins were membrane-associated or
      related to the extracellular matrix. In addition, four other proteins were
      identified to be differentially expressed in MEF-CM using high pressure liquid
      chromatography (HPLC) and cytokine arrays. In functional experiments where CM was
      replaced with six of the factors identified, hESC were able to proliferate for
      five continuous passages whilst maintaining 68-82% and 74-98% expression of
      pluripotent markers, Oct-4 and Tra-1-60, respectively. Using proteomic tools,
      important proteins from CM that supports hESC culture have been identified, which
      when replaced with recombinant proteins, continue to support undifferentiated
      hESC growth in a feeder-free culture platform.

PMID- 17544537
TI  - Penicillium brasilianum as an enzyme factory; the essential role of feruloyl
      esterases for the hydrolysis of the plant cell wall.
AB  - The production of arabinoxylan-degrading enzymes by the fungus Penicillium
      brasilianum, grown on different carbon and nitrogen sources as well as different
      environmental conditions was investigated. Highest feruloyl esterase (225 mU/ml)
      and alpha-L-arabinofuranosidase (211 mU/ml) activities were obtained when P.
      brasilianum was grown on sugar beet pulp, whereas maximum xylanase (17 U/ml)
      activity was found during growth on oat spelt xylan. Yeast extract was the
      preferable nitrogen source for the production of all the three enzymes. Further
      optimization of the production of the crude enzyme mixture was examined by
      experimental design using a D-optimal quadratic model. Investigation of the
      microbial regulation of enzyme production showed that the presence of free
      ferulic acid further stimulated the production and pointing to that the fungal
      regulatory mechanism involved a coordinated production and secretion of feruloyl
      esterase, xylanase and alpha-L-arabinofuranosidase. Since agroindustrial by
      products are a potential source of phenolic acids, crude enzyme mixtures of P.
      brasilianum were tested for their hydrolysis abilities against eight complex or
      model substrates. While total release of phenolic acids and pentoses was not
      observed, the synergistic enhancement of hydrolysis in the presence of feruloyl
      esterase was clearly demonstrated.

PMID- 17544538
TI  - Particle shape: a new design parameter for micro- and nanoscale drug delivery
      carriers.
AB  - Encapsulation of therapeutic agents in polymer particles has been successfully
      used in the development of new drug carriers. A number of design parameters that
      govern the functional behavior of carriers, including the choice of polymer,
      particle size and surface chemistry, have been tuned to optimize their
      performance in vivo. However, particle shape, which may also have a strong impact
      on carrier performance, has not been thoroughly investigated. This is perhaps due
      to the limited availability of techniques to produce non-spherical polymer
      particles. In recent years, a number of reports have emerged to directly address
      this bottleneck and initial studies have indeed confirmed that particle shape can
      significantly impact the performance of polymer drug carriers. This article
      provides a review of this field with respect to methods of particle preparation
      and the role of particle shape in drug delivery.

PMID- 17544539
TI  - Fibrinolytic dysfunction after gestation is associated to components of insulin
      resistance and early type 2 diabetes in latino women with previous gestational
      diabetes.
AB  - Among patients with metabolic syndrome (MS), atherosclerosis and abnormal
      fibrinolytic function are frequently present, mostly owing to an increase in
      plasminogen activator inhibitor-1(PAI-1). We analyze PAI-1 in pregnant women,
      both normal and with gestational diabetes (GDM) and postpartum regarding its
      correlation to MS surrogates. Clinical characteristics, glucose tolerance (100g
      OGTT), lipids, PAI-1 antigen, insulin sensitivity (HOMA-S), and pancreatic beta
      cell function (HOMA-B) were investigated in 34 women. Eleven had normal glucose
      tolerance (NGT) during pregnancy and 23 had GDM (all GAD antibodies-negative).
      All patients were studied at 28-34 weeks of gestation and 16-24 weeks after
      delivery (75 g-OGTT). Parameters of interest were determined using commercial
      test systems. During pregnancy, PAI-1 was not statistically different between NGT
      and GDM (47+/-25 ng/ml versus 47+/-28 ng/ml, p=0.9). After gestation, 19 (56%)
      women had NGT (11 of them from previous NGT group) and 15 (44%) had impaired
      glucose tolerance (IGT) or DM. The IGT (IGT+DM) group had higher PAI-1 (p=0.01),
      which did not decreased after delivery NGT-NGT before and after delivery (47+/-25
      ng/ml versus 6+/-5 ng/ml; p<0.001), GDM-NGT (62+/-36 ng/ml versus 14+/-15 ng/ml;
      p=0.001) and GDM-IGT (39+/-20 ng/ml versus 27+/-23 ng/ml; p=0.15). PAI-1 levels
      were positively correlated (p<0.05) to total cholesterol (r(s)=0.37),
      triglycerides (r(s)=0.48), fasting plasma glucose (r(s)=0.52), 2-h plasma glucose
      in the OGTT (r(s)=0.58) and were negatively correlated (p<0.05) with HOMA-S
      (r(s)=-0.42) and HOMA-B (r(s)=-0.38). Fibrinolytic dysfunction is still present
      in GDM women and is associated with early development of IGT or T2DM. PAI
      correlated with surrogate markers of MS levels and may identify a group of women
      at risk for macroangiopathy.

PMID- 17544540
TI  - Change in prevalence and 6-year incidence of diabetes and impaired fasting
      glucose in Korean subjects living in a rural area.
AB  - AIMS: To determine the change in prevalence, incidence and risk factors
      associated with diabetes and impaired fasting glucose (IFG) in a rural Korean
      area. METHODS: Initially a total of 1119 subjects (424 men and 695 women) aged 31
      99 years were recruited in 1997. Baseline clinical data and various laboratory
      values were obtained. Six years later, we visited the same area and measured
      similar parameters in 814 subjects (316 men and 498 women) of which 558 were
      original participants and 256 subjects were new. Incidence and risk factors of
      diabetes were analyzed in 518 subjects. Diabetes and IFG were defined according
      to American Diabetes Association criteria. RESULTS: Age- and sex-adjusted
      prevalence of diabetes in 1997 was 6.9%, increasing to 11.7% in 2003. The
      prevalence of IFG increased alarmingly from 21.9% in 1997 to 38.8% in 2003. The
      age- and sex-adjusted incidence rate of diabetes was 16.3 per 1000 person-years.
      Baseline fasting plasma glucose, 2h post-load glucose, abdominal circumference
      and urinary albumin excretion rate (UAER) acted as independent risk factors for
      diabetes in a multivariate logistic regression analysis. CONCLUSIONS: The
      prevalence of diabetes and IFG increased markedly from 1997 to 2003, indicating
      the need for urgent preventive measures. Fasting and 2h post-load glucose,
      abdominal circumference and UAER independently predicted the development of
      diabetes in this rural Korean population.

PMID- 17544541
TI  - Stochastic modelling of insulin sensitivity and adaptive glycemic control for
      critical care.
AB  - Targeted, tight model-based glycemic control in critical care patients that can
      reduce mortality 18-45% is enabled by prediction of insulin sensitivity, S(I).
      However, this parameter can vary significantly over a given hour in the
      critically ill as their condition evolves. A stochastic model of S(I) variability
      is constructed using data from 165 critical care patients. Given S(I) for an
      hour, the stochastic model returns the probability density function of S(I) for
      the next hour. Consequently, the glycemic distribution following a known
      intervention can be derived, enabling pre-determined likelihoods of the result
      and more accurate control. Cross validation of the S(I) variability model shows
      that 86.6% of the blood glucose measurements are within the 0.90 probability
      interval, and 54.0% are within the interquartile interval. "Virtual Patients"
      with S(I) behaving to the overall S(I) variability model achieved similar
      predictive performance in simulated trials (86.8% and 45.7%). Finally, adaptive
      control method incorporating S(I) variability is shown to produce improved
      glycemic control in simulated trials compared to current clinical results. The
      validated stochastic model and methods provide a platform for developing advanced
      glycemic control methods addressing critical care variability.

PMID- 17544542
TI  - Matrices and scaffolds for protein delivery in tissue engineering.
AB  - The tissue engineering of functional tissues depends on the development of
      suitable scaffolds to support three dimensional cell growth. To improve the
      properties of the scaffolds, many cell carriers serve dual purposes; in addition
      to providing cell support, cutting-edge scaffolds biologically interact with
      adhering and invading cells and effectively guide cellular growth and development
      by releasing bioactive proteins like growth factors and cytokines. To design
      controlled release systems for certain applications, it is important to
      understand the basic principles of protein delivery as well as the stability of
      each applied biomolecule. To illustrate the enormous progress that has been
      achieved in the important field of controlled release, some of the recently
      developed cell carriers with controlled release capacity, including both solid
      scaffolds and hydrogel-derived scaffolds, are described and possible solutions
      for unresolved issues are illustrated.

PMID- 17544543
TI  - Enhanced sensitivity of protein kinase B/Akt to insulin in hypoxia is independent
      of HIF1alpha and promotes cell viability.
AB  - Maintenance of oxygen homeostasis is a key requirement to ensure normal mammalian
      cell growth and differentiation. Hypoxia arises when oxygen demand exceeds
      supply, and is a feature of multiple human diseases including stroke, cancer and
      renal fibrosis. We have investigated the effect of hypoxia on kidney cells, and
      observed that insulin-induced cell viability is increased in hypoxia. We have
      characterized the role of protein kinase B (PKB/Akt) in these cells as a
      potential mediator of this effect. PKB/Akt activity was increased by low oxygen
      concentrations in kidney cells, and insulin-stimulated activation of PKB/Akt was
      stronger, more rapid and more sustained in hypoxia. Reduction of HIF1alpha levels
      using antimycin-A or siRNA targeting HIF1alpha did not affect PKB/Akt activation
      in hypoxia. Pharmacologic stabilization of HIF1alpha independent of hypoxia did
      not increase insulin-stimulated PKB/Akt activation. Although increased insulin
      stimulated cell viability was observed in hypoxia, no differences in the degree
      of insulin-stimulated glucose uptake were observed in L6 muscle cells in hypoxia
      compared to normoxia. Thus, PKB/Akt may regulate specific cellular responses to
      growth factors such as insulin under adverse conditions such as hypoxia.

PMID- 17544544
TI  - Curt Richter and the female rat.
AB  - Richter fully appreciated the fundamental biological importance of sex
      differences, in particular the challenges of female reproductive function to the
      two classes of behavior that most engaged him, endogenous rhythms and "self
      regulatory" behaviors. Indeed, his contributions in these areas justify honoring
      him as one of the founders of behavioral neuroendocrinology. During the 1920s
      Richter, together with Wang, Kinder and other students, performed elegant
      phenomenological and mechanistic studies of sex differences in rats' spontaneous
      locomotor activity, nest building, and food intake. All of these behaviors
      display rhythms entrained to the ovarian cycle in female rats, and Richter's
      analyses of them formed the bases of many current areas of behavioral
      neuroscience. Slightly later, Richter made fundamentally important discoveries
      related to nutrient self-selection in pregnant and lactating rats, including
      changes in micronutrient and macronutrient selection. These data played a major
      role in the development of his concept of behavioral regulation of homeostasis.
      Unfortunately, some of these discoveries are rarely recalled. This is both
      historically regrettable and potentially an impediment to contemporary research
      progress.

PMID- 17544545
TI  - Post-discharge surgical site infection surveillance by automated telephony.
AB  - Surgical site infection (SSI) is an important outcome indicator after surgery and
      is part of a national programme of surveillance in Scotland. Post-discharge
      surveillance has important cost implications for both primary and acute areas of
      the NHS and it is therefore important to establish a robust method to obtain
      these data. This study used an automated telephony system to gain information on
      SSI developing post-discharge. The patients included were those who had inpatient
      surveillance carried out following hip and knee replacements, and cardiac
      surgery. A recorded message was used to ask the patient questions concerning the
      state of their wound. These questions were answered by pressing numbers on their
      phone. The study population was 104 and there were 18 patients who thought they
      had a wound infection but after clarification only nine patients suffered a post
      discharge SSI. The number of patients who responded with at least one call to the
      system was 62. Although this pilot study was carried out with small numbers, it
      was felt that with certain refinements it should continue to be used for post
      discharge surgical site surveillance of infection.

PMID- 17544546
TI  - Liberation of urotensin II from the teleost urophysis: an historical overview.
AB  - During the past 20 years, urotensin II (UII) has progressed from being a peptide
      synthesized only in the urophysis of the caudal neurosecretory system of teleost
      fish to being considered an important physiological regulator in mammals with
      implications for the pathogenesis of a range of human cardiovascular and renal
      diseases. The "liberation" of UII from the urophysis was a gradual process and
      involved the sequential realization that (a) UII is present not only in the
      urophysis but also in the central nervous systems (CNS) of teleosts, (b) UII
      peptides, similar in structure to the urophysial peptides, are present in the
      diffuse caudal neurosecretory systems and/or CNS of species less evolutionarily
      advanced than teleosts, including Agnatha, thereby showing that UII is a
      phylogenetically ancient peptide, (c) UII is present in the brain and spinal cord
      of a tetrapod, the green frog Rana ridibunda, and (d) the UII gene and its
      specific receptor (GPR14/UT) are expressed in the CNS and certain peripheral
      tissues of mammals, including the human. The discovery that the genomes of
      mammals contain an additional gene encoding a UII-related peptide (URP) and the
      availability of highly effective peptide and non-peptide antagonists to
      investigate the role of UII in human physiology and pathophysiology ensure that
      the peptide will remain "center stage" for several years to come.

PMID- 17544547
TI  - Reduced 5-HT2A receptor binding in patients with mild cognitive impairment.
AB  - Previous studies of patients with Alzheimer's disease (AD) have described reduced
      brain serotonin 2A (5-HT(2A)) receptor density. It is unclear whether this
      abnormality sets in early in the course of the disease and whether it is related
      to early cognitive and neuropsychiatric symptoms. We assessed cerebral 5-HT(2A)
      receptor binding in patients with mild cognitive impairment (MCI) and related 5
      HT(2A) receptor binding to clinical symptoms. Sixteen patients with MCI of the
      amnestic type (mean age 73, mean MMSE 26.1) and 17 age and sex matched control
      subjects were studied with MRI and [(18)F]altanserin PET in a bolus-infusion
      approach. A significant global reduction of 20-30% in 5-HT(2A) binding (atrophy
      corrected) was found in most neocortical areas. Reduced 5-HT(2A) binding in the
      striatum correlated significantly with Neuropsychiatric Inventory depression and
      anxiety scores. We conclude that widespread reductions in 5-HT(2A) receptor
      binding were found in amnestic MCI, pointing at the presence of serotonergic
      dysfunction in prodromal AD. This may provide some of the pathophysiological
      background for the neuropsychiatric symptoms found in early AD.

PMID- 17544548
TI  - Air to lung partition coefficients for volatile organic compounds and blood to
      lung partition coefficients for volatile organic compounds and drugs.
AB  - Values of in vitro gas to lung partition coefficients, K(lung), of VOCs have been
      collected from the literature. For 44 VOCs, application of the Abraham solvation
      equation to log K(lung) yielded a correlation with R(2)=0.968 and S.D.=0.25 log
      units. Combination of the log K(lung) values with log K(blood) values leads to in
      vitro blood to lung partition coefficients, log P(lung) for 43 VOCs; an Abraham
      solvation equation correlated these values with a very poor R(2)=0.262 but with a
      very good S.D.=0.190 log units. Values of in vivo log P(lung) for 80 drugs were
      collected, and were correlated with R(2)=0.647 and S.D.=0.51 log units. When the
      log P(lung) values for VOCs and drugs were combined, an Abraham solvation
      equation could correlate the 123 compounds with R(2)=0.676 and S.D.=0.43 log
      units. Division of the 123 compounds into a training set and a test set, showed
      that the training equation could predict log P(lung) values with an average error
      of 0.001 and a standard deviation of 0.44 log units; for drugs in the combined
      test set the average error was 0.02 and the standard deviation 0.43 log units.

PMID- 17544549
TI  - Design of a multispecies probiotic mixture to prevent infectious complications in
      critically ill patients.
AB  - BACKGROUND & AIMS: Although the potential for probiotics is investigated in an
      increasing variety of diseases, there is little or no consensus regarding the
      desired probiotic properties for a particular disease in question, nor about the
      final design of the probiotic. Specific strain selection procedures were
      undertaken to design a disease-specific multispecies probiotic. METHODS: From a
      strain collection of 69 different lactic acid bacteria a primary selection was
      made of 14 strains belonging to different species showing superior survival in a
      simulated gastrointestinal environment. Functional tests like antimicrobial
      activity against a range of clinical isolates and cytokine inducing capacity in
      cultured human peripheral blood mononuclear cells were used to further identify
      potential strains. RESULTS: Specific strains inhibited growth of clinical
      isolates whereas others superiorly induced the anti-inflammatory cytokine IL-10.
      Based on functional tests and general criteria regarding probiotic design and
      safety, a selection of the following six strains was made (Ecologic 641);
      Bifidobacterium bifidum, Bifidobacterium infantis, Lactobacillus acidophilus,
      Lactobacillus casei, Lactobacillus salivarius and Lactococcus lactis. Combination
      of these strains resulted in a wider antimicrobial spectrum, superior induction
      of IL-10 and silencing of pro-inflammatory cytokines as compared to the
      individual components. CONCLUSIONS: Application of strict criteria during the
      design of a disease-specific probiotic prior to implementation in clinical trials
      may provide a rational basis for use of probiotics.

PMID- 17544550
TI  - Issues surrounding standardization of meningococcal group W135 serology.
AB  - Group W135 polysaccharide vaccines were licensed without efficacy trials using
      the serum bactericidal antibody (SBA) assay as a surrogate of protection.
      Standardization of group A and C SBA assays has been largely achieved. However,
      no such efforts have been focussed on W135. Although W135 strains have been
      recommended by WHO for polysaccharide production, no such recommendation are in
      place for use in immunoassays. Strain characterization is of importance as W135
      strains may possess either an O-acetylated or de-O-acetylated polysaccharide
      capsule and the human immune response can vary according to the O-acetylation of
      the target antigen. Following conjugate or polysaccharide vaccination, few data
      are published with respect to complement source comparisons although both human
      and baby rabbit sera have been utilized with similar end points. In studies of
      natural immunity subcapsular antigens are primarily the target antigens and thus
      strain choice for use in the SBA assay is important. International
      standardization of assays is necessary to allow for comparisons of data over time
      and place.

PMID- 17544551
TI  - Co-immunisation with DNA encoding RANK/RANKL or 4-1BBL costimulatory molecules
      does not enhance effector or memory CTL responses afforded by immunisation with a
      tumour antigen-encoding DNA vaccine.
AB  - T cell mediated immune responses are induced following interaction of MHC
      presented epitope on professional antigen presenting cells such as dendritic
      cells (DCs) with cognate T cell receptor. Up-regulation of receptor-ligand pairs
      of costimulatory molecules linking DC to T cell enhances the resulting T cell
      responses. This 'second signalling' occurs through the B7 molecules CD80/86
      expressed by DCs, and importantly through members of the TNF ligand/TNF receptor
      superfamilies. We have previously shown that co-expression of RANK/RANKL or 41BB
      L in addition to tumour antigen in dendritic cells augmented cognate effector and
      memory tumour antigen-directed cytotoxic T cell responses when the DCs were used
      to immunise mice. Here, we examined whether co-immunisation with naked plasmid
      DNAs encoding antigen and these costimulatory molecule(s), would enhance antigen
      specific T cell responses. We demonstrate that co-immunisation with DNAs encoding
      tumour antigen and costimulatory molecules failed to enhance antigen-directed CTL
      responses, or tumour protection, afforded by immunisation with DNA encoding
      tumour antigen alone.

PMID- 17544552
TI  - Monitoring of adverse events during the 2003 mass vaccination campaign with a
      trivalent meningococcal A/C/W135 polysaccharide vaccine in Burkina Faso.
AB  - During a mass campaign with a newly licensed meningococcal polysaccharide ACW135
      vaccine in Burkina Faso, adverse events following immunization (AEFI) were
      monitored up to 4 weeks after the campaign. Eighty-six AEFI cases (5.9 cases per
      100,000 vaccine doses distributed) were reported. Among 22 serious events, 4
      severe local reactions were considered very likely and 4 severe allergic
      reactions were considered probably related to the vaccination. One fatal case in
      a child followed protracted seizures of undetermined cause. In a setting with no
      prior surveillance system, adverse events were reported at rates comparable to
      documented rates for meningococcal polysaccharide vaccines in other settings. The
      findings confirm the benefits of the vaccine in the control of meningococcal
      meningitis.

PMID- 17544553
TI  - Selenium bioavailability and uptake as affected by four different plants in a
      loamy clay soil with particular attention to mycorrhizae inoculated ryegrass.
AB  - The aim of this study was to investigate the influence of plant species,
      especially of their rhizosphere soil, and of inoculation with an arbuscular
      mycorrhizal (AM) fungus on the bioavailability of selenium and its transfer in
      soil-plant systems. A pot experiment was performed with a loamy clay soil and
      four plant species: maize, lettuce, radish and ryegrass, the last one being
      inoculated or not with an arbuscular mycorrhizal fungus (Glomus mosseae). Plant
      biomass and Se concentration in shoots and roots were estimated at harvest. Se
      bioavailability in rhizosphere and unplanted soil was evaluated using sequential
      extractions. Plant biomass and selenium uptake varied with plant species. The
      quantity of rhizosphere soil also differed between plants and was not
      proportional to plant biomass. The highest plant biomass, Se concentration in
      plants, and soil to plant transfer factor were obtained with radish. The lowest
      Se transfer factors were obtained with ryegrass. For the latter, mycorrhizal
      inoculation did not significantly affect plant growth, but reduced selenium
      transfer from soil to plant by 30%. In unplanted soil after 65 days aging, more
      than 90% of added Se was water-extractable. On the contrary, Se concentration in
      water extracts of rhizosphere soil represented less than 1% and 20% of added Se
      for ryegrass and maize, respectively. No correlation was found between the water
      extractable fraction and Se concentration in plants. The speciation of selenium
      in the water extracts indicated that selenate was reduced, may be under organic
      forms, in the rhizosphere soil.

PMID- 17544554
TI  - Mutations in SH3BP2, the cherubism gene, were not detected in central or
      peripheral giant cell tumours of the jaw.
AB  - Giant cell granulomas of the jaw (GCGJ) are non-familial, generally unilateral
      osteoclast-rich lesions that are histopathologically indistinguishable from
      cherubism. Cherubism is an autosomal dominant disease that is characterised by
      bilateral radiolucencies of the jaw, and caused by mutations that occur in SH3BP2
      exon 10. The aim of the study was to screen lesional GCGJ tissue for SH3BP2
      mutations. Lesional mononuclear stromal or spindle cells were microdissected from
      paraffin-embedded tissue from GCGJ, and DNA was then extracted and sequenced for
      SH3BP2 mutations associated with cherubism. No mutations were detected in 26 GCGJ
      (15 central, 11 peripheral), which indicated that people with GCGJ do not harbour
      cherubism-related germline SH3BP2 mutations, and that GCGJ do not harbour somatic
      SH3BP2 mutations. This suggests that cherubism and GCGJ arise on a different
      genetic background, and therefore detection of SH3BP2 mutations can be a useful
      means of distinguishing between them.

PMID- 17544555
TI  - Investigation into the effect of varus-valgus orientation on load transfer in the
      resurfaced femoral head: a multi-femur finite element analysis.
AB  - BACKGROUND: Femoral head resurfacing is a popular procedure for younger active
      hip replacement patients. Whilst the current generation of metal-on-metal
      resurfacing arthroplasties appear to have cured the osteolysis problems that
      plagued earlier resurfacing implants, fracture of the femoral head and aseptic
      loosening are still factors of concern in its survivorship. Several studies have
      shown a tendency towards failure in resurfaced femurs where the implant has been
      set at a varus angle. This work aims to investigate the influence of varus-valgus
      orientation on load transfer within the resurfaced proximal femur. METHODS: This
      study uses Computer Tomography based finite element analysis to determine the
      effect of implant orientation on load transfer in the proximal femur with respect
      to the intact femur. A group of 16 femurs were studied to take into account inter
      patient variation; four models were produced for each femur, one of the intact
      femur, one resurfaced with the implant set inline with the femoral neck and one
      each representing varus and valgus implant alignment. FINDINGS: Results showed
      the valgus aligned resurfaced femur to produce strain patterns more akin to the
      intact femur. As the implant's angle to the femoral shaft increases from varus to
      valgus the strains in the superior femoral neck are reduced while those in the
      inferior neck are increased. INTERPRETATION: The study concluded that valgus
      alignment of the resurfacing arthroplasty is preferential to varus alignment; as
      it induces a more physiological strain pattern and reduces the risk of femoral
      neck fracture. These findings are in line with clinical experience, which has
      shown an increase of failure with varus implanted prostheses.

PMID- 17544556
TI  - Biomonitoring seasonal variation of urban air polycyclic aromatic hydrocarbons
      (PAHs) using Ficus benghalensis leaves.
AB  - Temporal and seasonal variations of polycyclic aromatic hydrocarbons (PAHs)
      concentrations in leaves of Ficus benghalensis were investigated in Varanasi city
      (India). Leaf samples were collected from six sites from urban area of Varanasi
      and from a control site. PAH extraction was done by sonication in dichloromethane
      acetone and quantification by GC-MS. In January total leaf PAHs concentrations at
      all the urban sites were twice higher as compared to other season's viz. summer
      and rainy. In contrast, at the control site leaf PAHs concentrations showed lower
      values than urban sites. The maximum concentrations of total PAHs in winter were
      due to the medium molecular weight PAHs which increases with respect to both low
      and high molecular weight PAHs. The temporal variation of medium molecular weight
      PAHs was similar both at the urban and remote sites. These results support
      biomonitoring ability of Ficus benghalensis leaves to temporal variations in PAHs
      contamination.

PMID- 17544557
TI  - Work in the metal industry and nasopharyngeal cancer mortality among formaldehyde
      exposed workers.
AB  - OBJECTIVE: To investigate further the possibility that the large nasopharyngeal
      cancer (NPC) mortality excess among a cohort of formaldehyde-exposed workers may
      be related to occupational factors external to the study plant. METHODS: Subjects
      were 7345 workers employed at a plastics-producing plant (1941-1984) in
      Wallingford, Connecticut evaluated independently as part of a National Cancer
      Institute cohort study. Vital status for 98% of the cohort and cause of death for
      95% of 2872 deaths were determined through 2003. Reconstructed worker exposures
      to formaldehyde were used to compute unlagged and lagged exposure measures. We
      computed standardized mortality ratios (SMRs) based on US and local county rates.
      In a nested case-control study we evaluated mortality risks from NPC and from all
      other pharyngeal cancers combined (AOPC) in relation to formaldehyde exposure
      while accounting for potential confounding or effect modification by smoking or
      external (non-Wallingford) employment. Job applications, Connecticut commercial
      city directories and a previous survey were used to assign subjects to three
      external job groups. RESULTS: We observed no new deaths from NPC and one
      additional AOPC death (pharynx unspecified) yielding, respectively, SMRs of 4.43
      (7 deaths, 95% CI=1.78-9.13) and 1.71 (16 deaths, 95% CI=1.01-2.72). Five of
      seven NPC cases worked in silver smithing (including brass plating and other jobs
      related to silver or brass) or other metal work (including steel working and
      welding), and this type of work was relatively rare in the remaining study
      population (OR=14.41, 95% CI=1.08-82.1). For AOPC, we found a moderate increase
      in risk for other metal work (OR=1.40, 95% CI=.31-5.1). Interaction models
      suggested that NPC and AOPC risks were not elevated in subjects exposed only to
      formaldehyde. CONCLUSIONS: The results of our nested case-control study suggest
      that the large nasopharyngeal cancer mortality excess in the Wallingford cohort
      may not be due to formaldehyde exposure, but rather reflects the influence of
      external employment in the ferrous and non-ferrous metal industries of the local
      area that entailed possible exposures to several suspected risk factors for upper
      respiratory system cancer (e.g., sulfuric acid mists, mineral acid, metal dusts
      and heat). Our findings may also help to explain why the associations with
      formaldehyde and nasopharyngeal cancer reported in the 1994 update of the 10
      plant NCI formaldehyde cohort study were unique to the Wallingford plant (Plant 1
      in NCI study). Further updates of the NCI formaldehyde cohort study should
      include co-exposure data on silver smithing and other metal work for all study
      plants to help explain the unique findings for nasopharyngeal cancer in Plant 1
      compared with the other nine plants.

PMID- 17544558
TI  - Can theory-based messages in combination with cognitive prompts promote exercise
      in classroom settings?
AB  - A randomised control trial evaluated the effectiveness of a theory-based
      persuasive leaflet designed to encourage students to undertake at least one
      additional physical exercise session a week. Participants were 503 secondary
      school students attending a school in South-East England. The leaflet was written
      to target potentially modifiable cognitive antecedents of exercise specified by
      the Theory of Planned Behaviour. It was separately augmented with two cognitive
      change techniques, resulting in three intervention conditions, leaflet alone;
      leaflet plus motivational quiz, and leaflet plus implementation intention prompt,
      as well as a no-leaflet control condition. Cognitions and behaviour were measured
      immediately before and 3 weeks after intervention. The results showed that all
      three-leaflet interventions significantly increased reported exercise, intention
      to exercise and related cognitions, compared to the control condition, but did
      not differ in their impact. Mediation analysis showed that intervention effects
      on exercise were partially mediated by intentions and perceived behavioural
      control.

PMID- 17544559
TI  - Effects of perfluorooctane sulfonate on tracheal ciliary beating frequency in
      mice.
AB  - Perfluorooctane sulfonate (PFOS) is one of the emerging persistent organic
      pollutants, ubiquitously found in the global environment, even in human serum.
      PFOS has been reported to perturb Ca(2+) homeostasis in Paramecium,
      cardiomyocytes and neurons. Since ciliary beat frequency (CBF) in the trachea is
      known to be increased by cytoplasmic Ca(2+) elevation, the effects of PFOS on CBF
      were evaluated in a slice preparation using video-enhanced contrast microscopy.
      PFOS increased CBF by 11% (P<0.05) at 100 microM, while it did not do so at 30
      microM. At 100 microM, it increased intracellular Ca(2+) concentration
      ([Ca(2+)](i)) in mouse tracheal ciliary cells. In Ca(2+)-free solution, PFOS at
      100 microM failed to increase CBF (0.96-fold of vehicle control). The addition of
      Gd(3+) (1 microM), a store-operated Ca(2+) channel blocker, did not prevent the
      increase in CBF (1.09-fold (P<0.01) of vehicle control). High extracellular K(+)
      concentration (50 mM), which causes depolarization of the plasma membrane
      potential and a transient increase in [Ca(2+)](i), increased CBF by 20% (P<0.05).
      This observation indicates involvement of voltage-dependent Ca(2+) channels
      (VDCCs) in stimulation of CBF. Nifedipine (30 microM), a selective VDCC blocker,
      antagonized the effects of high K(+) (0.92-fold of high K(+) solution) and PFOS
      (0.96-fold of vehicle control) on CBF. In cells from peroxisome proliferator
      activated receptor alpha (PPARalpha)-null mice, PFOS still increased CBF (1.12
      fold (P<0.05) of vehicle control), indicating that the actions of PFOS are not
      mediated via PPARalpha. These findings collectively suggest that PFOS stimulates
      CBF by increasing cytoplasmic Ca(2+) through VDCC.

PMID- 17544560
TI  - Effects of toothbrushes with tapered and cross angled soft bristle design on
      dental plaque and gingival inflammation: a randomized and controlled clinical
      trial.
AB  - OBJECTIVE: To investigate the effect of three manual toothbrushes on dental
      plaque and gingival inflammation. METHODS: The elmex Sensitive Extra Soft (ESES),
      elmex Sensitive Soft (ESS) and an ADA standard toothbrush (ADAS) were evaluated
      in a randomized clinical trial. Subjects brushed twice daily in their usual
      manner. Plaque index (PI), gingival index (GI) and plaque and gingival scores of
      interproximal spaces (IntPI and IntGI) were evaluated at day 15 and day 30. ANOVA
      and t-test were used to compare plaque and gingival scores. RESULTS: A total of
      84 subjects with mild to moderate gingivitis completed the study. Plaque and
      gingival scores in ESES and ESS groups decreased from baseline to day 15 and day
      30. At day 30, subjects in both ESES and ESS groups had lower plaque and gingival
      scores than those in the ADAS group (p<0.05). In the ESES group, PI reduced by
      13.6% (p<0.0001), and GI by 10.5% (p<0.0001) at day 30 when compared to the
      baseline scores. In the ESS group, PI reduced by 11.8% (p<0.0001), and GI by
      12.0% (p<0.0001) at day 30. The reduction in IntPI and IntGI scores were
      comparable to those of the overall PI and GI. In contrast, there were no changes
      in PI, GI, and IntPI and IntGI scores between baseline and the day 15 and day 30
      evaluations in the ADAS group. CONCLUSIONS: Both the ESES and ESS toothbrushes
      are more effective in removing dental plaque and reducing gingival inflammation
      than the ADA standard toothbrush.

PMID- 17544562
TI  - The correlation between clinical characteristics of preeclampsia and the
      concentration of fetal DNA in maternal circulation.

PMID- 17544561
TI  - The role of type I interferon production by dendritic cells in host defense.
AB  - Type I interferons (IFN) and dendritic cells (DC) share an overlapping history,
      with rapidly accumulating evidence for vital roles for both production of type 1
      IFN by DC and the interaction of this IFN both with DC and components of the
      innate and adaptive immune responses. Within the innate immune response, the
      plasmacytoid DC (pDC) are the "professional" IFN producing cells, expressing
      specialized toll-like receptors (TLR7 and -9) and high constitutive expression of
      IRF-7 that allow them to respond to viruses with rapid and extremely robust IFN
      production; following activation and production of IFN, the pDC subsequently
      mature into antigen presenting cells that help to shape the adaptive immune
      response. However, like most cells in the body, the myeloid or conventional DC
      (mDC or cDC) also produce type I IFNs, albeit typically at a lower level than
      that observed with pDC, and this IFN is also important in innate and adaptive
      immunity induced by these classic antigen presenting cells. These two major DC
      subsets and their IFN products interact both with each other as well as with NK
      cells, monocytes, T helper cells, T cytotoxic cells, T regulatory cells and B
      cells to orchestrate the early immune response. This review discusses some of the
      converging history of DC and IFN as well as mechanisms for IFN induction in DC
      and the effects of this IFN on the developing immune response.

PMID- 17544563
TI  - Use of oxytocin to prevent haemorrhage at caesarean section--a survey of practice
      in the United Kingdom.
AB  - OBJECTIVE: To establish the views and current practice of obstetricians and
      anaesthetists with regard to the use of oxytocin to prevent haemorrhage at
      caesarean section. STUDY DESIGN: A national survey of all lead consultant
      obstetricians and anaesthetists for the labour ward in the United Kingdom. A
      postal questionnaire was sent to all clinicians with one subsequent reminder to
      non-responders. The use of oxytocin bolus and infusion, perceived side effects of
      intravenous oxytocin, estimated blood loss at caesarean section, and willingness
      to participate in a future clinical trial were explored. RESULTS: The response
      rate was 84% (365 respondents). A slow bolus of 5 IU oxytocin was the preferred
      approach of obstetricians and anaesthetists (153, 86% and 171, 92%,
      respectively). Oxytocin infusions were used routinely by 72 clinicians (20%) with
      selective use for particular clinical circumstances by 289 (80%). Most clinicians
      used either 30 IU (158, 43%) or 40 IU (192, 53%) infusions over 4h, with a total
      of 38 different regimens. The perceived risk of side effects with an oxytocin
      infusion was low. Estimated "average" blood loss varied (150-1,500 ml) with 56
      clinicians (17%) and 93 (28%) reporting a >20% risk of postpartum haemorrhage for
      elective and emergency caesarean sections, respectively. CONCLUSION: There is
      wide variation in the use of oxytocin at caesarean section reflecting limited
      research in this area. Excess haemorrhage is considered to occur frequently and
      the perceived risk of oxytocin bolus and infusion is low. Further research is
      required addressing the optimal use of oxytocic agents at caesarean section.

PMID- 17544564
TI  - On the origin of the decrease in stability of the DNA hairpin d(GCGAAGC) on
      complexation with aromatic drugs.
AB  - Molecular dynamics simulations of drug-DNA complexes have been carried out in
      order to explain the experimentally observed decrease in thermal stability of the
      DNA hairpin d(GCGAAGC) on binding the aromatic drug molecules, daunomycin,
      ethidium bromide, novantrone and proflavine. This complexation behavior is in
      contrast to the stabilizing effect of the same aromatic drug molecules on DNA
      duplexes. Analysis of the energy parameters and the hydration properties of the
      complexes shows that the main factor correlating with the decrease in melting
      temperatures of the drug-hairpin complexes is the number of water bridges, with a
      reduction of at least 40% on ligand binding.

PMID- 17544565
TI  - Green reconstruction of the tsunami-affected areas in India using the integrated
      coastal zone management concept.
AB  - A tsunami, triggered by a massive undersea earthquake off Sumatra in Indonesia,
      greatly devastated the lives, property and infrastructure of coastal communities
      in the coastal states of India, Andaman and Nicobar Islands, Indonesia, Sri
      Lanka, Malaysia and Thailand. This event attracted the attention of environmental
      managers at all levels, local, national, regional and global. It also shifted the
      focus from the impact of human activities on the environment to the impacts of
      natural hazards. Recovery/reconstruction of these areas is highly challenging. A
      clear understanding of the complex dynamics of the coast and the types of
      challenges faced by the several stakeholders of the coast is required. Issues
      such as sustainability, equity and community participation assume importance. The
      concept of ICZM (integrated coastal zone management) has been effectively used in
      most parts of the world. This concept emphasizes the holistic assessment of the
      coast and a multidisciplinary analysis using participatory processes. It
      integrates anthropocentric and eco-centric approaches. This paper documents
      several issues involved in the recovery of tsunami-affected areas and recommends
      the application of the ICZM concept to the reconstruction efforts.

PMID- 17544566
TI  - Influence of temporal insonation window quality on the assessment of cerebral
      autoregulation with transcranial Doppler sonography.
AB  - Cerebral autoregulation can be assessed quickly and noninvasively using
      transcranial Doppler sonography (TCD). A poor transtemporal insonation window is
      a common limitation in TCD examinations. The effects of insonation quality on TCD
      autoregulation measurements have never been investigated. We developed two
      methods to quantitatively measure insonation quality. We also validated a model
      to artificially worsen the insonation window. This involves inserting a thin
      aluminium foil between the TCD probe and the skin. Forty-six healthy volunteers
      underwent TCD examination before and after artificial reduction of the
      transtemporal insonation quality. Two autoregulation parameters, the phase
      difference (PD) and a cross-correlation coefficient (Mx), were calculated from
      the recordings. The aluminium foil model realistically simulates poor insonation
      conditions, producing a decrease in the signal power from 36.4 +/- 2.8 dB to 32.0
      +/- 1.5 dB. In corrupted insonation windows, the PD is artificially low (native:
      34.2 +/- 9.3 degrees , corrupted: 29.9 +/- 9.7 degrees , p = 0.002), but the Mx
      is not significantly different. Insonation quality may introduce a systematic
      bias of clinically relevant magnitude into TCD-based cerebral autoregulation
      studies. This must be considered when studies of elderly patients are planned.
      This article discusses strategies to account for this bias.

PMID- 17544567
TI  - Reproducibility of sonographic measurement of the substantia nigra.
AB  - The aim of this study was to evaluate inter-reader, intra-investigator and inter
      investigator reproducibility and correlations in the assessment of substantia
      nigra (SN) echogenicity and area measurement by a physician-sonographer (PS), a
      sonographic laboratory assistant (SLA) and a physician without sonographic
      experience (PN). A total of 22 patients with extrapyramidal symptoms were
      examined using transcranial sonography (TCS). SN images were encoded and
      evaluated by the three readers. A second TCS examination was performed after 7+/
      2 d. A second investigator performed TCS examination 1 mo later. Spearman rank
      correlation and Pearson's correlation coefficient were used when assessing the
      agreement between readers. All three readers identified the same 15 patients with
      SN echogenicity III or more. Inter-reader SN echogenicity and area measurement
      correlations were r=0.55 to 0.82 and r=0.31 to 0.74 between PS and SLA and r=0.55
      to 0.77 and 0.49 to 0.62 between PS and PN, respectively (p<0.05 in all cases).
      Intra-reader echogenicity and area measurement correlations (r=0.85 to 0.96 and
      r=0.51 to 0.69) were statistically significant only for PS (p<0.001). All intra-
      and inter-investigator correlations of SN area measurement (r=0.69 to 0.88 and
      r=0.5 to 0.61) and SN echogenicity (r=0.64 to 0.92 and r=0.51 to 0.69) were
      statistically significant (p<0.05). Semiquantitative evaluation of SN
      echogenicity and area using TCS is highly dependent on the experience of the
      sonographer. Only an experienced sonographer was able to produce very
      reproducible results with statistically significant correlations; SLA and PN
      intra-reader correlations were poor.

PMID- 17544568
TI  - Can therapeutic ultrasound influence the integration of skin grafts?
AB  - Therapeutic ultrasound (TUS) is a widely used coadjuvant physical means to
      promote biological tissue repair. In the present investigation, the influence of
      TUS on the integration of full-thickness skin graft was studied in rabbits.
      Twenty female adult rabbits were used and two 2x2-cm square full-thickness skin
      grafts were obtained from both scapular regions and swapped, the one cut out on
      the right being placed on the left and vice versa. The graft on the right was
      irradiated with TUS (3 MHz, 0.5 W/cm2, 5-min duration) once a day for seven
      consecutive days, beginning on the third postoperative day; the graft on the left
      was submitted to simulated irradiation. The animals were killed on the 11th day
      and the grafted areas were resected (graft+safety margin) for histological
      examination. Five-mum-thick sections were alternatively stained with Gomori's
      trichrome, proliferating cell nuclear antigen (PCNA) and picrosirius red and
      examined under the light microscope, and the epidermal and dermal areas were
      measured and proliferating cells and new blood vessels counted. The results
      showed a significant increase (p=0.007) in the number of proliferating epidermal
      cells (12.18% and 7.34% of the total number of cells in the irradiated and
      control grafts, respectively) and new blood vessels per field (p=0.0001) in the
      irradiated grafts (6.27 compared with 3.07). Despite the increased number of
      proliferating cells and blood vessels, there was no significant difference
      between the epidermis (246,392 microm2 and 200,626 microm2 in groups 1 and 2,
      respectively; p=0.07) and dermis (2,157,730 microm2 and 2,109,150 microm2 in
      groups 1 and 2, respectively; p=0.21) areas as a function of thickness for both
      groups. We conclude that TUS induces morphological alterations in biological
      processes, such as epidermic germinative layer cell proliferation and
      neoangiogenesis, which are involved in the integration of full-thickness skin
      grafts. This has a potential for clinical use in humans.

PMID- 17544569
TI  - Quantitative ultrasound of phalanges of adults with end-stage renal disease or
      who have undergone renal transplantation.
AB  - In patients with end-stage renal disease (ESRD), bone disturbances are common.
      The aim of this study was to compare the bone mineral status in patients with
      ESRD, in patients post renal transplantation and in healthy controls. The groups
      were composed of 218 males and 126 females (ESRD), 43 males and 23 females (renal
      transplantation) and 614 males and 927 females (healthy controls). Skeletal
      status was evaluated by quantitative ultrasound measurements of the phalanges
      using a DBM 1200 (IGEA, Carpi, Italy), which measures the amplitude-dependent
      speed of sound (Ad-SoS) in m/s. Data analyses were performed with Statistica 6
      for Windows (StatSoft, Inc., Tulsa, OK, USA). The Z-scores in gender subgroups
      were significantly lower in patients undergoing dialysis and after
      transplantation than in controls (p<0.00001). The Z-scores did not differ between
      gender subgroups after transplantation and the Z-scores of dialyzed males were
      significantly better than in females (p<0.00001). The mean value of Z-scores in
      patients after transplantation was significantly lower than in all patients with
      ESRD (p<0.05) and in males (p<0.01). The duration of dialysis negatively
      influenced the Ad-SoS; however, the time elapsed since transplantation did not.
      The cumulative corticosteroid dose did not correlate with skeletal variables. In
      conclusion, patients with ESRD treated with hemodialysis and postrenal
      transplantation patients, across both genders, were observed to have skeletal
      disturbances.

PMID- 17544570
TI  - Editorial comment on: local progression among men with conservatively treated
      localized prostate cancer: results from the transatlantic prostate group.

PMID- 17544571
TI  - Re: Hamid Mazdak, Iraj Meshki and Fatemeh Ghassami. Effect of mitomycin C on
      anterior urethral stricture recurrence after internal urethrotomy. Eur Urol
      2007;51:1089-92.

PMID- 17544572
TI  - Local progression among men with conservatively treated localized prostate
      cancer: results from the Transatlantic Prostate Group.
AB  - OBJECTIVES: Men with clinically detected localized prostate cancer treated
      without curative intent are at risk of complications from local tumor growth. We
      investigated rates of local progression and need for local therapy among such
      men. METHODS: Men diagnosed with prostate cancer during 1990-1996 were identified
      from cancer registries throughout the United Kingdom. Inclusion criteria were age
      < or =76 yr at diagnosis, PSA level < or =100 ng/ml, and, within 6 mo after
      diagnosis, no radiation therapy, radical prostatectomy, evidence of metastatic
      disease, or death. Local progression was defined as increase in clinical stage
      from T1/2 to T3/T4 disease, T3 to T4 disease, and/or need for transurethral
      resection of the prostate (TURP) to relieve symptoms >6 mo after cancer
      diagnosis. RESULTS: The study included 2333 men with median follow-up of 85 mo
      (range: 6-174). Diagnosis was by TURP in 1255 men (54%), needle biopsy in 1039
      (45%), and unspecified in 39 (2%). Only 29% were treated with hormonal therapy
      within 6 mo of diagnosis. Local progression occurred in 335 men, including 212
      undergoing TURP. Factors most predictive of local progression on multivariable
      analysis were PSA at diagnosis and Gleason score of the diagnostic tissue
      (detrimental), and early hormonal therapy (protective). We present a nomogram
      that predicts the likelihood of local progression within 120 mo after diagnosis.
      CONCLUSIONS: Men with clinically detected localized prostate cancer managed
      without curative intent have an approximately 15% risk for local progression
      within 10 yr of diagnosis. Among those with progression, the need for treatment
      is common, even among men diagnosed by TURP. When counseling men who are
      candidates for management without curative intent, the likelihood of symptoms
      from local progression must be considered.

PMID- 17544573
TI  - Arteriovenous fistula originating from proximal part of the anterior cerebral
      artery.
AB  - Intracerebral arteriovenous fistulas of the brain may be misdiagnosed as
      arteriovenous malformation. There are only a few reports in the literature about
      this concept and to the best of our knowledge this is the first case arising from
      the proximal part of the anterior cerebral artery in association with an aneurysm
      that ruptured. A 64-year-old man presented with subarachnoid hemorrhage. The
      patient was neurologically intact. Cerebral angiography and magnetic resonance
      imaging of the patient revealed a small arteriovenous malformation of the brain
      involving the region of gyrus rectus and the posteromedial aspect of the
      orbitofrontal gyrus in addition to an aneurysmal dilatation within the
      malformation. An arteriovenous fistula arising from the junction of the A1 and A2
      segments of the right anterior cerebral artery connected to a vein that has
      tributaries spreading over the fronto-orbital gyrus and gyrus rectus, were
      observed during surgery. The patient was successfully treated with clip
      ligatation of the fistula. Intracerebral arteriovenous fistulas are rare lesions.
      They may easily be misdiagnosed as arteriovenous malformations. There
      preoperative consideration in the differential diagnosis can help to decide the
      most appropriate treatment option.

PMID- 17544574
TI  - A novel ECGF1 mutation in a Thai patient with mitochondrial neurogastrointestinal
      encephalomyopathy (MNGIE).
AB  - Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a rare autosomal
      recessive, multisystem disorder, which is clinically defined by ptosis,
      ophthalmoparesis, gastrointestinal dysmotility, cachexia, peripheral neuropathy,
      and leukoencephalopathy. MNGIE is caused by mutations in the nuclear gene,
      endothelial cell growth factor 1 (ECGF1), encoding thymidine phosphorylase (TP).
      ECGF1 mutations cause severe loss of TP activity, abnormal accumulations of
      thymidine and deoxyuridine in plasma, and alterations of mitochondrial DNA. Here,
      we report the first Thai patient with MNGIE confirmed genetically by the
      identification of a homozygous novel ECGF1 gene mutation, c.100insC, which causes
      a frameshift and premature truncation of TP protein.

PMID- 17544575
TI  - Intramedullary ependymoma associated with Lhermitte-Duclos disease and Cowden
      syndrome.
AB  - The authors describe the case of a 45-year-old man with progressive gait ataxia
      and sensorimotor deficits of the upper and lower extremities. The patient had
      been diagnosed earlier with Lhermitte-Duclos disease (LDD) in the left cerebellar
      hemisphere and Cowden syndrome (CS). MR imaging studies revealed an intraspinal
      tumor at C6-C7. Microsurgical gross total resection of the tumor was achieved.
      Histolopathological examination revealed an intramedullary ependymoma.
      Postoperatively, neurological deficits gradually improved. This is the first
      reported case of ependymoma in a patient with LDD and CD. Coexistence of an
      intraspinal ependymoma with cerebellar LDD and CS appears to be rare, but can
      lead to treatment failure if missed.

PMID- 17544576
TI  - Critical wind velocity for arresting upwind gas and smoke dispersion induced by
      near-wall fire in a road tunnel.
AB  - In case of a tunnel fire, toxic gas and smoke particles released are the most
      fatal contaminations. It is important to supply fresh air from the upwind side to
      provide a clean and safe environment upstream from the fire source for people
      evacuation. Thus, the critical longitudinal wind velocity for arresting fire
      induced upwind gas and smoke dispersion is a key criteria for tunnel safety
      design. Former studies and thus, the models built for estimating the critical
      wind velocity are all arbitrarily assuming that the fire takes place at the
      centre of the tunnel. However, in many real cases in road tunnels, the fire
      originates near the sidewall. The critical velocity of a near-wall fire should be
      different with that of a free-standing central fire due to their different plume
      entrainment process. Theoretical analysis and CFD simulation were performed in
      this paper to estimate the critical velocity for the fire near the sidewall.
      Results showed that when fire originates near the sidewall, it needs larger
      critical velocity to arrest the upwind gas and smoke dispersion than when fire at
      the centre. The ratio of critical velocity of a near-wall fire to that of a
      central fire was ideally estimated to be 1.26 by theoretical analysis. Results by
      CFD modelling showed that the ratio decreased with the increase of the fire size
      till near to unity. The ratio by CFD modelling was about 1.18 for a 500kW small
      fire, being near to and a bit lower than the theoretically estimated value of
      1.26. However, the former models, including those of Thomas (1958, 1968),
      Dangizer and Kenndey (1982), Oka and Atkinson (1995), Wu and Barker (2000) and
      Kunsch (1999, 2002), underestimated the critical velocity needed for a fire near
      the tunnel sidewall.

PMID- 17544577
TI  - Photolytic (UVC) and photocatalyic (UVC/TiO2) decomposition of pyridines.
AB  - The degradation of 2-chloropyridine (2-CPY) and its degradation primary product 2
      hydroxypyridine (2-HPY) was studied by means of ultraviolet (UV) irradiation at
      254nm. Photolytic and photocatalytic experiments were conducted on 2-CPY and 2
      HPY aqueous solutions in a batch reactor with internal recycle in laminar and
      turbulent conditions at 50 degrees C in a closed but not airtight system with and
      without additional aeration, at solution ambient pH and at controlled pH
      conditions, with use and in the absence of radical scavenger. The solution volume
      was 0.4L and initial substrate concentrations were approximately 2.6mmol/L (0.25
      0.3g/L depending on the substrate). Where applicable 1g/L TiO(2) (P-25) was used,
      suspended in the liquid in a form of turbulent slurry or using a glass tube
      around the UV-lamp on which a fixed TiO(2) catalytic layer had been deposited. At
      the aforementioned conditions 2-CPY readily degrades photolytically, the
      catalytic path having very little influence. In all cases 2-CPY produces 2-HPY
      which further degrades to other products. Aeration, pH and the presence of
      catalyst and/or radical scavengers do not affect the rate of decomposition of 2
      CPY, but have a strong influence on the further decomposition of the produced 2
      HPY. 2-HPY decomposition proceeds both catalytically and photolytically following
      oxygen dependent and oxygen independent pathways.

PMID- 17544578
TI  - Adsorbents for capturing mercury in coal-fired boiler flue gas.
AB  - This paper reviews recent advances in the research and development of sorbents
      used to capture mercury from coal-fired utility boiler flue gas. Mercury
      emissions are the source of serious health concerns. Worldwide mercury emissions
      from human activities are estimated to be 1000 to 6000 t/annum. Mercury emissions
      from coal-fired power plants are believed to be the largest source of
      anthropogenic mercury emissions. Mercury emissions from coal-fired utility
      boilers vary in total amount and speciation, depending on coal types, boiler
      operating conditions, and configurations of air pollution control devices
      (APCDs). The APCDs, such as fabric filter (FF) bag house, electrostatic
      precipitator (ESP), and wet flue gas desulfurization (FGD), can remove some
      particulate-bound and oxidized forms of mercury. Elemental mercury often escapes
      from these devices. Activated carbon injection upstream of a particulate control
      device has been shown to have the best potential to remove both elemental and
      oxidized mercury from the flue gas. For this paper, NORIT FGD activated carbon
      was extensively studied for its mercury adsorption behavior. Results from bench-,
      pilot- and field-scale studies, mercury adsorption by coal chars, and a case of
      lignite-burned mercury control were reviewed. Studies of brominated carbon,
      sulfur-impregnated carbon and chloride-impregnated carbon were also reviewed.
      Carbon substitutes, such as calcium sorbents, petroleum coke, zeolites and fly
      ash were analyzed for their mercury-adsorption performance. At this time,
      brominated activated carbon appears to be the best-performing mercury sorbent. A
      non-injection regenerable sorbent technology is briefly introduced herein, and
      the issue of mercury leachability is briefly covered. Future research directions
      are suggested.

PMID- 17544579
TI  - Synthesis, characterization and structure effects on preconcentration and
      extraction of N,N'-bis-(salicylaldehydene)-1,4-bis-(p-aminophenoxy) butane
      towards some divalent cations.
AB  - Separation with solvent extraction of Cu(II), Co(II) and Ni(II) from aqueous
      solution using N,N'-bis-(salicylaldehydene)-1,4-bis-(p-aminophenoxy)butane
      (H(2)L) as the new extractant has been studied. The new Schiff base, was
      synthesized by reaction of 1,4-bis-(p-aminophenoxy)butane and salicylaldehyde.
      Microanalytical data, elemental analysis, UV-vis (1)H NMR and (13)C NMR spectra
      and IR-spectra were used to confirm the structures. The extractability and
      selectivity of divalent cations was evaluated as a function of relationship
      between distribution ratios of the metal and pH or ligand concentration. Cu(+2)
      showed the highest extractability and selectivity at pH 7.8, whereas Ni(+2) and
      Co(+2) showed at pH 9.2. From the loaded organic phase, Cu(II), Co(II), Ni(II)
      stripping were carried out in one stage with aqueous acid solution including
      various concentrations of HCl. The stripping efficiency was found to be
      quantitative in case of 1.5M HCl. From quantitative evaluation of the extraction
      equilibrium data, it has been deduced that the complexes extracted are the simple
      1:1 chelates, CuL, CoL, NiL.

PMID- 17544580
TI  - Analysis of styrene-butadiene-styrene polymer modified bitumen using fluorescent
      microscopy and conventional test methods.
AB  - This paper presents a laboratory study of modified bitumen containing styrene
      butadiene-styrene (SBS) copolymer. Polymer modified bitumen (PMB) samples have
      been produced by mixing a 50/70 penetration grade unmodified (base) bitumen with
      SBS Kraton D1101 copolymer at five different polymer contents. The fundamental
      characteristics of the SBS PMB samples have been determined using conventional
      methods. The morphology of the samples as well as the percent area (%)
      distribution of SBS polymers throughout the base bitumen have been characterized
      and determined by means of fluorescence microscopy and Qwin Plus image analysis
      program, respectively. The mechanical properties of the hot-mix asphalt (HMA)
      containing SBS PMBs have also been analyzed and compared with HMA incorporating
      base bitumen. The effect of polymer addition on the short and long term aging
      characteristics of HMA have been evaluated by indirect tensile strength (ITS)
      test. The results indicated that polymer modification improved the conventional
      properties (penetration, softening point, etc.) and the mechanical properties
      (Marshall, ITS, etc.) of the base bitumen. It was also concluded that at low
      polymer contents, the samples revealed the existence of dispersed polymer
      particles in a continuous bitumen phase, whereas at high polymer contents a
      continuous polymer phase has been observed. Moreover, it was found out that the
      polymer addition minimizes the short and long term aging of HMA.

PMID- 17544581
TI  - Oxidation and isomerization of cyclohexane catalyzed by SO42-/Fe2O3-CoO under
      mild condition.
AB  - SO(4)(2-)/Fe(2)O(3)-CoO solid catalyst was prepared and characterized by X-ray
      diffraction (XRD), scanning electron microscope (SEM) and Fourier transfer
      infrared (FT-IR) spectroscopy. Its catalytic activities in oxidation and
      isomerization of cyclohexane in air under mild condition were studied by UV,
      GC/MS and XPS. The results suggested that isomerization and oxidation of
      cyclohexane under mild conditions can synchronously performed and the catalytic
      activity of the catalyst can be improved by promotion of Co element into the
      sulfated iron. The high catalytic activities of catalysts may be related to the
      shift of the asymmetric stretching frequency of the SO bonds of sulfate species.
      Finally, the possible mechanism was also proposed.

PMID- 17544582
TI  - Consequence analysis to determine the damage to humans from vapour cloud
      explosions using characteristic curves.
AB  - The aim of this paper is to provide a methodology to facilitate consequence
      analysis for vapour cloud explosions (VCE). Firstly, the main PROBIT equations to
      evaluate direct damage on humans from those accidents (eardrum rupture, death due
      to skull fracture, death due to whole body impact and lung damage) are discussed
      and the most suitable ones are selected. Secondly, a new methodology is developed
      to relate characteristic overpressure-impulse-distance curves for VCE, obtained
      in a previous paper (F. Diaz Alonso et al., Characteristic overpressure-impulse
      distance curves for vapour cloud explosions using the TNO Multi-Energy model, J.
      Hazard. Mater. A137 (2006) 734-741) with the selected PROBIT equations. This
      methodology allows the determination of damage as a function of distance to the
      accident's origin in only one step, using explosion energy and VCE Multi-Energy
      charge strength as input parameters.

PMID- 17544583
TI  - Efficacy and safety of imidacloprid/moxidectin spot-on solution and fenbendazole
      in the treatment of dogs naturally infected with Angiostrongylus vasorum
      (Baillet, 1866).
AB  - A randomized, blinded, controlled multicentre field trial study was conducted to
      evaluate the efficacy and safety of imidacloprid 10%/moxidectin 2.5% spot-on
      solution and fenbendazole in treating dogs naturally infected with
      Angiostrongylus vasorum. Dogs were randomly treated either with a single dose of
      0.1 ml/kg bodyweight of imidacloprid 10%/moxidectin 2.5% spot-on solution or with
      25 mg/kg bodyweight fenbendazole per os for 20 days. The study period was 42 days
      with dogs being examined on days 0, 7 and 42. The primary efficacy parameter was
      the presence of L1 larvae in faecal samples evaluated by a Baermann test from
      three consecutive days. Thoracic radiographs performed on each visit were being
      taken as a paraclinical parameter to support the results of the Baermann test.
      Twenty-seven dogs in the imidacloprid/moxidectin group and 23 dogs in the
      fenbendazole group completed the study according to protocol. The efficacies of
      the two treatment protocols were 85.2% (imidacloprid/moxidectin) and 91.3%
      (fenbendazole) with no significant difference between treatment groups. On
      radiographic evaluation pulmonary parenchyma showed similar improvement in each
      group. No serious adverse effects to treatment were recorded: most of the minor
      adverse effects were gastrointestinal such as diarrhea (nine dogs), vomitus
      (eight dogs) and salivation (three dogs). In general, these adverse effects were
      of short duration (1-2 days) within the first few days after treatment start and
      required little or no treatment. This prospective study demonstrates that both
      treatment protocols used are efficacious under field conditions, that treatment
      of mildly to moderately infected dogs with either of these protocols is safe and
      yields an excellent prognosis for recovering from the infection.

PMID- 17544584
TI  - Four disulfide-bridged scorpion beta neurotoxin CssII: heterologous expression
      and proper folding in vitro.
AB  - The gene of the four disulfide-bridged Centruroides suffusus suffusus toxin II
      was cloned into the expression vector pQE30 containing a 6His-tag and a FXa
      proteolytic cleavage region. This recombinant vector was transfected into
      Escherichia coli BL21 cells and expressed under induction with isopropyl
      thiogalactoside (IPTG). The level of expression was 24.6 mg/l of culture medium,
      and the His tagged recombinant toxin (HisrCssII) was found exclusively in
      inclusion bodies. After solubilization the HisrCssII peptide was purified by
      affinity and hydrophobic interaction chromatography. The reverse-phase HPLC
      profile of the HisrCssII product obtained from the affinity chromatography step
      showed several peptide fractions having the same molecular mass of 9392.6 Da,
      indicating that HisrCssII was oxidized forming several distinct disulfide bridge
      arrangements. The multiple forms of HisrCssII after reduction eluted from the
      column as a single protein component of 9400.6 Da. Similarly, an in vitro folding
      of the reduced HisrCssII generated a single oxidized component of HisrCssII,
      which was cleaved by the proteolytic enzyme FXa to the recombinant CssII
      (rCssII). The molecular mass of rCssII was 7538.6 Da as expected. Since native
      CssII (nCssII) is amidated at the C-terminal residue whereas the rCssII is
      heterologously expressed in the format of free carboxyl end, there is a
      difference of 1 Da, when comparing both peptides (native versus heterologously
      expressed). Nevertheless, they show similar toxicity when injected intracranially
      into mice, and both nCssII and rCssII show the typical electrophysiological
      properties of beta-toxins in Na(v)1.6 channels, which is for the first time
      demonstrated here. Binding and displacement experiments conducted with
      radiolabelled CssII confirms the electrophysiological results. Several problems
      associated with the heterologously expressed toxins containing four disulfide
      bridges are discussed.

PMID- 17544585
TI  - Epstein-Barr virus-targeted immunotherapy for nasopharyngeal carcinoma.
AB  - Epstein-Barr virus (EBV) is constantly present in undifferentiated and poorly
      differentiated nasopharyngeal cancer. Thus, tumour-associated viral antigens are
      potential targets for immunotherapy. Recently, both preclinical and early
      clinical studies have shown that various strategies can enhance EBV-specific
      immunity. Moreover, significant anti-tumour effect has been observed, and was
      generally correlated with biological response. The present review discusses the
      rational for EBV-targeted immunotherapy and summarises the latest developments in
      this area.

PMID- 17544586
TI  - Depolarization-induced, glutamate receptor-mediated, and transactivation
      dependent extracellular-signal regulated kinase phosphorylation in cultured
      cerebellar granule neurons.
AB  - Depolarization of 7-8-day-old mouse cerebellar granule neurons in primary
      cultures, a glutamatergic preparation, by elevation of the extracellular
      potassium ion concentration ([K+]e) to 45 mM induces an increase of
      phosphorylation of extracellular-signal regulated kinase 1 and 2 (ERK1/2) at two
      time periods: 20 min and 60 min after the [K+]e increase. This effect can be
      mimicked by 5 min of exposure to 50 microM glutamate, suggesting that ERK1/2
      phosphorylation in response to the depolarization is brought about by the
      resulting glutamate release. This concept is supported by the observation that
      the K+ -mediated stimulation of phosphorylation at both times is inhibited by MK
      801, an NMDA antagonist, and by CNQX, an AMPA/kainate antagonist. These
      antagonists also inhibit the response to glutamate. Both increases in ERK1/2
      phosphorylation are also inhibited by GM 6001 (a metalloproteinase inhibitor,
      preventing 'shedding' of growth factors), by AG 1478 (a receptor tyrosine kinase
      inhibitor, preventing epidermal growth factor [EGF] receptor activation), and
      also partly by heparin (inactivating heparin-binding epidermal growth factor [HB
      EGF]), suggesting transactivation of epidermal growth factor receptors (EGFR).
      Transactivation is an intracellular/extracellular signal transduction pathway in
      which release from receptor- or depolarization-stimulated cells of EGFR ligand(s)
      (including HB-EGF), catalyzed by a metalloproteinase, stimulates receptor
      tyrosine kinases on the same (an autocrine effect) or adjacent (a paracrine
      effect) cells. The expression of HB-EGF as well as of transforming growth factor
      alpha (TGF-alpha), two of the EGFR ligands, in the cells was confirmed by reverse
      transcription polymerase chain reaction, and the only partial inhibition by
      heparin suggests that both of these EGFR agonists are involved. Such a
      transactivation may play a major role in glutamate-mediated signaling and
      plasticity.

PMID- 17544588
TI  - Predictors of cannabis use in men with and without psychosis.
AB  - BACKGROUND: Factors associated with cannabis use among people with psychosis are
      not well understood. AIMS: To examine whether people with psychosis and age
      matched controls modified cannabis use in response to recent experiences. METHOD:
      This study predicted 4 weeks of cannabis use prospectively, using expectancies
      derived from recent occasions of use. RESULTS: People with psychosis used
      cannabis less frequently than controls, but had more cannabis-related problems.
      More negative cannabis expectancies resulted in less frequent cannabis use over
      Follow-up. The psychosis group was more likely to moderate cannabis use after
      negative effects than controls. CONCLUSIONS: Results offer optimism about
      abilities of people with psychosis to moderate cannabis use in the short term.

PMID- 17544589
TI  - Social norms and alcohol consumption among intercollegiate athletes: the role of
      athlete and nonathlete reference groups.
AB  - The relationship between perceived alcohol use among peers and personal alcohol
      use was assessed in a sample of collegiate athletes. Data were collected on 109
      intercollegiate athletes during the competitive season and 119 athletes during
      the off-season at a large, state university in the Northeastern United States.
      Participants were asked to estimate the normative alcohol use of four reference
      groups (closest athlete friend, closest nonathlete friend, typical athlete, and
      typical nonathlete). Results of both in-season and off-season analyses indicated
      that athletes estimated that others consumed more drinks per week than they did,
      and perceptions of these social norms predicted personal use. Although the
      typical athlete norm emerged as the strongest predictor of personal alcohol use,
      the relative strength of the relationships between individual behavior and the
      athlete and nonathlete norms varied according to seasonal status. Results have
      implications for the content and timing of prevention and intervention programs
      aimed at reducing high-risk alcohol use among intercollegiate athletes.

PMID- 17544587
TI  - Glutamate receptor abnormalities in the YAC128 transgenic mouse model of
      Huntington's disease.
AB  - A yeast artificial chromosome (YAC) mouse model of Huntington's disease (YAC128)
      develops motor abnormalities, age-dependent striatal atrophy and neuronal loss.
      Alteration of neurotransmitter receptors, particularly glutamate and dopamine
      receptors, is a pathological hallmark of Huntington's disease. We therefore
      analyzed neurotransmitter receptors in symptomatic YAC128 Huntington's disease
      mice. We found significant increases in N-methyl-d-aspartate, AMPA and
      metabotropic glutamate receptor binding, which were not due to increases in
      receptor subunit mRNA expression levels. Subcellular fractionation analysis
      revealed increased levels of glutamate receptor subunits in synaptic membrane
      fractions from YAC128 mice. We found no changes in dopamine, GABA or adenosine
      receptor binding, nor did we see alterations in dopamine D1, D2 or adenosine A2a
      receptor mRNA levels. The receptor abnormalities in YAC128 transgenic mice thus
      appear limited to glutamate receptors. We also found a significant decrease in
      preproenkephalin mRNA in the striatum of YAC128 mice, which contrasts with the
      lack of change in levels of mRNA encoding neurotransmitter receptors. Taken
      together, the abnormal and selective increases in glutamate receptor subunit
      expression and binding are not due to increases in receptor subunit expression
      and may exert detrimental effects. The decrease in preproenkephalin mRNA suggests
      a selective transcriptional deficit, as opposed to neuronal loss, and could
      additionally contribute to the abnormal motor symptoms in YAC128 mice.

PMID- 17544590
TI  - Placental umbilical cord blood transfusion in acute ischaemic stroke.
AB  - Stroke is a major cause of neurological disability across all countries in the
      world. Functional recovery after stroke is limited because of neuronal death and
      degeneration. Although early reperfusion therapy may improve outcome,
      thrombolysis does not reverse ischaemic neuronal death and carries the risk of
      cerebral haemorrhage. Early trials of stem cell therapy in promoting functional
      recovery after completed stroke remain inconclusive. Based on experimental data,
      we propose human umbilical cord blood transfusion as a possible therapy for
      ischaemic cerebral stroke to aid functional recovery.

PMID- 17544591
TI  - Local recurrences after different treatment strategies for ductal carcinoma in
      situ of the breast: a population-based study in the East Netherlands.
AB  - PURPOSE: Outcomes after different treatment strategies for ductal carcinoma in
      situ (DCIS) of the breast were analyzed for a geographically defined population
      in the East Netherlands. METHODS AND MATERIALS: A total of 798 patients with a
      first diagnosis of DCIS between January 1989 and December 2003 were included and
      their medical records were reviewed. Survival rates for ipsilateral recurrences
      were calculated by the Kaplan-Meier method and a multivariate Cox proportional
      hazards regression model was used to evaluate the prognostic significance of
      different variables. RESULTS: The 5-year recurrence-free survival was 75% for
      breast conserving surgery (BCS) alone (237 patients) compared with 91% for BCS
      followed by radiation therapy (RT; 153 patients) and 99% for mastectomy (408
      patients, p < 0.01). Independent risk factors for local recurrences were
      treatment strategy, symptomatically detected DCIS, and presence of comedo
      necrosis. Margin status reached statistical significance only for patients
      treated by BCS (hazard ratio, 2.0; 95% confidence interval, 1.1-4.0) whereas
      significance of other prognostic variables did not change. CONCLUSIONS: In a
      defined population outside a trial setting, RT after BCS for DCIS lowered
      recurrence rates. Besides the use of RT, a microscopically complete excision of
      DCIS is essential. This is especially true for patients with symptomatically
      detected DCIS and with tumors that contain comedo necrosis, as these groups are
      at particular high risk for recurrent disease.

PMID- 17544592
TI  - Brain metastases from breast carcinoma: validation of the radiation therapy
      oncology group recursive partitioning analysis classification and proposition of
      a new prognostic score.
AB  - PURPOSE: To validate the Radiation Therapy Oncology Group Recursive Partitioning
      Analysis (RTOG RPA) classification and determine independent prognostic factors,
      to create a simple and specific prognostic score for patients with brain
      metastases (BM) from breast carcinoma treated with whole-brain radiotherapy
      (WBRT). METHODS AND MATERIALS: From January 1998 through December 2003, 132
      patients with BM from breast carcinoma were treated with WBRT. We analyzed
      several potential predictors of survival after WBRT: age, Karnofsky performance
      status, RTOG-RPA class, number of BM, presence and site of other systemic
      metastases, interval between primary tumor and BM, tumor hormone receptor (HR)
      status, lymphocyte count, and HER-2 overexpression. RESULTS: A total of 117
      patients received exclusive WBRT and were analyzed. Median survival with BM was 5
      months. One-year and 2-year survival rates were 27.6% (95% confidence interval
      [CI] 19.9-36.8%) and 12% (95% CI 6.5-21.2%), respectively. In multivariate
      analysis, RTOG RPA Class III, lymphopenia (< or =0.7 x 10(9)/L) and HR negative
      status were independent prognostic factors for poor survival. We constructed a
      three-factor prognostic scoring system that predicts 6-month and 1-year rates of
      overall survival in the range of 76.1-29.5% (p = 0.00033) and 60.9-15.9% (p =
      0.0011), respectively, with median survival of 15 months, 5 months, or 3 months
      for patients with none, one, or more than one adverse prognostic factor(s),
      respectively. CONCLUSIONS: This study confirms the prognostic value of the RTOG
      RPA classification, lymphopenia, and tumor HR status, which can be used to form a
      prognostic score for patients with BM from breast carcinoma.

PMID- 17544593
TI  - Diffusion tensor magnetic resonance imaging finding of discrepant fractional
      anisotropy between the frontal and parietal lobes after whole-brain irradiation
      in childhood medulloblastoma survivors: reflection of regional white matter
      radiosensitivity?
AB  - PURPOSE: To test the hypothesis that fractional anisotropy (FA) is more severely
      reduced in white matter of the frontal lobe compared with the parietal lobe after
      receiving the same whole-brain irradiation dose in a cohort of childhood
      medulloblastoma survivors. METHODS AND MATERIALS: Twenty-two medulloblastoma
      survivors (15 male, mean [+/- SD] age = 12.1 +/- 4.6 years) and the same number
      of control subjects (15 male, aged 12.0 +/- 4.2 years) were recruited for
      diffusion tensor magnetic resonance imaging scans. Using an automated tissue
      classification method and the Talairach Daemon atlas, FA values of frontal and
      parietal lobes receiving the same radiation dose, and the ratio between them were
      quantified and denoted as FFA, PFA, and FA(f/p), respectively. The Mann-Whitney U
      test was used to test for significant differences of FFA, PFA, and FA(f/p)
      between medulloblastoma survivors and control subjects. RESULTS: Frontal lobe and
      parietal lobe white matter FA were found to be significantly less in
      medulloblastoma survivors compared with control subjects (frontal p = 0.001,
      parietal p = 0.026). Moreover, these differences were found to be discrepant,
      with the frontal lobe having a significantly larger difference in FA compared
      with the parietal lobe. The FA(f/p) of control and medulloblastoma survivors was
      1.110 and 1.082, respectively (p = 0.029). CONCLUSION: Discrepant FA changes
      after the same irradiation dose suggest radiosensitivity of the frontal lobe
      white matter compared with the parietal lobe. Special efforts to address the
      potentially vulnerable frontal lobe after treatment with whole-brain radiation
      may be needed so as to balance disease control and treatment-related morbidity.

PMID- 17544594
TI  - Biopsy findings after breast conservation therapy for early-stage invasive breast
      cancer.
AB  - PURPOSE: To determine the patterns and factors predictive of positive ipsilateral
      breast biopsy after conservation therapy for early-stage breast cancer. METHODS
      AND MATERIALS: We performed a retrospective review of Stage I-II breast cancer
      patients initially treated with lumpectomy and radiotherapy between 1977 and
      1996, who later underwent post-treatment ipsilateral breast biopsies. RESULTS: A
      total of 223 biopsies were performed in 193 treated breasts: 171 single and 22
      multiple biopsies. Of the 223 biopsies, 56% were positive and 44% were negative
      for recurrence. The positive biopsy rate (PBR) was 59% for the first and 32% for
      subsequent biopsies. The median time to the first post-treatment biopsy was 49
      months. Of the patients with negative initial biopsy findings, 11% later
      developed local recurrence. The PBR was 40% among patients with physical
      examination findings only, 65% with mammographic abnormalities only, and 79% with
      both findings (p = 0.001). Analysis of the procedure type revealed a PBR of 86%
      for core and 58% for excisional biopsies compared with 28% for aspiration
      cytology alone (p = 0.025). The PBR varied inversely with age at the original
      diagnosis: 49% if >or=51 years, 57% if 36-50 years, and 83% if <or=35 years (p =
      0.05). The PBR correlated directly with the interval after radiotherapy: 49% if
      <or=60 months, 59% if 60.1-120 months, 77% if 120.1-180 months, and 100% if >180
      months after completing postlumpectomy radiotherapy (p = 0.01). The PBR was not
      linked with recurrence location, initial pathologic T or N stage, estrogen
      receptor/progesterone receptor status, or final pathologic margins (all p >or=
      0.15). CONCLUSION: After definitive radiotherapy for early-stage breast cancer, a
      greater PBR was associated with the presence of both mammographic and clinical
      abnormalities, excisional or core biopsies, younger age at the initial diagnosis,
      and longer intervals after radiotherapy completion.

PMID- 17544595
TI  - Changes in the pelvic anatomy after an IMRT treatment fraction of prostate
      cancer.
AB  - PURPOSE: To quantify the three-dimensional variations of pelvic anatomy after a
      single treatment fraction. METHODS AND MATERIALS: Forty-six prostate cancer
      patients underwent computed tomography (CT) scanning with an in-room CT-on-rail
      system, before and immediately after one intensity-modulated radiotherapy (IMRT)
      session. To study the soft-tissue anatomy changes, the pre- and post-treatment CT
      images were registered using the bony structure with an in-house image
      registration software system. The center of volume for both the prostate and
      seminal vesicles was used to assess the relative displacement of the same
      structure after the treatment fraction. RESULTS: During one treatment fraction
      (21 +/- 4 min), both the prostate and seminal vesicles showed statistically
      significant systematic trends in the superior and anterior directions of the
      patient's anatomy. The net increase in bladder volume was huge (127 +/- 79
      cm(3)), yet this change did not translate into large target displacements.
      Although the population mean displacements in either direction were 1.3 +/- 2.9
      mm for the prostate and 1.2 +/- 4.1 mm for the seminal vesicles in the anterior
      direction, a few patients had displacements as large as 8.4 mm and 15.6 mm,
      respectively. These large displacements correlated strongly (p < 0.001) with
      large rectal volume increases caused by gaseous build-up in the rectum.
      CONCLUSION: The observed intrafraction variations in anatomy during prostate IMRT
      sessions suggest that, for any given fraction, the organ motion and volume
      changes can potentially lead to compromised target coverage in about 15% of
      patients in whom the prostate position shifted >4 mm.

PMID- 17544596
TI  - Treatment-planning study of prostate cancer intensity-modulated radiotherapy with
      a Varian Clinac operated without a flattening filter.
AB  - PURPOSE: To assess the feasibility of intensity-modulated radiotherapy for
      prostate cancer using photon beams from an accelerator operated without a
      flattening filter; and to determine potential benefits and drawbacks of using
      unflattened beams for this type of treatment. METHODS AND MATERIALS: Intensity
      modulated radiotherapy plans were generated for 10 patients with early-stage
      prostate cancer. For each patient, four plans were generated: with and without
      the flattening filter, at 6 and 18 MV. The prescription dose was 75.6 Gy to 98%
      of the planning target volume. The number of beams, their orientations, and
      optimization constraints were the same for all plans. Plans were generated with
      Eclipse 8.0 (Varian Medical Systems). RESULTS: All the plans developed with
      unflattened beams were clinically acceptable. In terms of patient dose
      distributions, plans with unflattened beams were similar to the corresponding
      plans with flattened beams. Plans with unflattened beams required fewer monitor
      units (MUs) per plan: on average, by a factor of 2.0 at 6 MV and 2.6 at 18 MV,
      assuming that removal of the flattening filter was not followed by recalibration
      of MUs. CONCLUSIONS: Clinically acceptable intensity-modulated radiotherapy plans
      for prostate cancer can be developed with unflattened beams at both 6 and 18 MV.
      Dosimetrically, flattened and unflattened beams generated similar treatment
      plans. The plans with unflattened beams required substantially fewer MUs. The
      reduction in the number of MUs indicates corresponding reduction in beam-on time
      and in the amount of radiation outside the target.

PMID- 17544597
TI  - Isotope and patient age predict for PSA spikes after permanent prostate
      brachytherapy.
AB  - PURPOSE: To evaluate prostate-specific antigen (PSA) spikes after permanent
      prostate brachytherapy in low-risk patients. METHODS AND MATERIALS: The study
      population consisted of 164 prostate cancer patients who were part of a
      prospective randomized trial comparing (103)Pd and (125)I for low-risk disease.
      Of the 164 patients, 61 (37.2%) received short-course androgen deprivation
      therapy. The median follow-up was 5.4 years. On average, 11.1 post-treatment PSA
      measurements were obtained per patient. Biochemical disease-free survival was
      defined as a PSA level of < or =0.40 ng/mL after nadir. A PSA spike was defined
      as an increase of > or =0.2 ng/mL, followed by a durable decline to prespike
      levels. Multiple parameters were evaluated as predictors for a PSA spike.
      RESULTS: Of the 164 patients, 44 (26.9%) developed a PSA spike. Of the 46 hormone
      naive (125)I patients and 57 hormone-naive (103)Pd patients, 21 (45.7%) and 8
      (14.0%) developed a PSA spike. In the hormone-naive patients, the mean time
      between implantation and the spike was 22.6 months and 18.7 months for (125)I and
      (103)Pd, respectively. In patients receiving neoadjuvant androgen deprivation
      therapy, the incidence of spikes was comparable between isotopes ((125)I 28.1%
      and (103)Pd 20.7%). The incidence of spikes was substantially different in
      patients <65 years vs. > or =65 years old (38.5% vs. 16.3%). On multivariate Cox
      regression analysis, patient age (p < 0.001) and isotope (p = 0.002) were
      significant predictors for spike. CONCLUSION: In low-risk prostate cancer, PSA
      spikes are most common in patients implanted with (125)I and/or <65 years of age.
      Differences in isotope-related spikes are most pronounced in hormone-naive
      patients.

PMID- 17544598
TI  - Intensity-modulated radiotherapy results in significant decrease in clinical
      toxicities compared with conventional wedge-based breast radiotherapy.
AB  - PURPOSE: We have previously demonstrated that intensity-modulated radiotherapy
      (IMRT) with a static multileaf collimator process results in a more homogenous
      dose distribution compared with conventional wedge-based whole breast irradiation
      (WBI). In the present analysis, we reviewed the acute and chronic toxicity of
      this IMRT approach compared with conventional wedge-based treatment. METHODS AND
      MATERIALS: A total of 172 patients with Stage 0-IIB breast cancer were treated
      with lumpectomy followed by WBI. All patients underwent treatment planning
      computed tomography and received WBI (median dose, 45 Gy) followed by a boost to
      61 Gy. Of the 172 patients, 93 (54%) were treated with IMRT, and the 79 patients
      (46%) treated with wedge-based RT in a consecutive fashion immediately before
      this cohort served as the control group. The median follow-up was 4.7 years.
      RESULTS: A significant reduction in acute Grade 2 or worse dermatitis, edema, and
      hyperpigmentation was seen with IMRT compared with wedges. A trend was found
      toward reduced acute Grade 3 or greater dermatitis (6% vs. 1%, p = 0.09) in favor
      of IMRT. Chronic Grade 2 or worse breast edema was significantly reduced with
      IMRT compared with conventional wedges. No difference was found in cosmesis
      scores between the two groups. In patients with larger breasts (> or =1,600
      cm(3), n = 64), IMRT resulted in reduced acute (Grade 2 or greater) breast edema
      (0% vs. 36%, p <0.001) and hyperpigmentation (3% vs. 41%, p = 0.001) and chronic
      (Grade 2 or greater) long-term edema (3% vs. 30%, p = 0.007). CONCLUSION: The use
      of IMRT in the treatment of the whole breast results in a significant decrease in
      acute dermatitis, edema, and hyperpigmentation and a reduction in the development
      of chronic breast edema compared with conventional wedge-based RT.

PMID- 17544599
TI  - Dosimetric feasibility of hypofractionated proton radiotherapy for neoadjuvant
      pancreatic cancer treatment.
AB  - PURPOSE: To evaluate tumor and normal tissue dosimetry of a 5 cobalt gray
      equivalent (CGE) x 5 fraction proton radiotherapy schedule, before initiating a
      clinical trial of neoadjuvant, short-course proton radiotherapy for pancreatic
      adenocarcinoma. METHODS AND MATERIALS: The first 9 pancreatic cancer patients
      treated with neoadjuvant intensity-modulated radiotherapy (1.8 Gy x 28) at the
      Massachusetts General Hospital had treatment plans generated using a 5 CGE x 5
      fraction proton regimen. To facilitate dosimetric comparisons, clinical target
      volumes and normal tissue volumes were held constant. Plans were optimized for
      target volume coverage and normal tissue sparing. RESULTS: Hypofractionated
      proton and conventionally fractionated intensity-modulated radiotherapy plans
      both provided acceptable target volume coverage and dose homogeneity. Improved
      dose conformality provided by the hypofractionated proton regimen resulted in
      significant sparing of kidneys, liver, and small bowel, evidenced by significant
      reductions in the mean doses, expressed as percentage prescribed dose, to these
      structures. Kidney and liver sparing was most evident in low-dose regions (< or
      =20% prescribed dose for both kidneys and < or =60% prescribed dose for liver).
      Improvements in small-bowel dosimetry were observed in high- and low-dose
      regions. Mean stomach and duodenum doses, expressed as percentage prescribed
      dose, were similar for the two techniques. CONCLUSIONS: A proton radiotherapy
      schedule consisting of 5 fractions of 5 CGE as part of neoadjuvant therapy for
      adenocarcinoma of the pancreas seems dosimetrically feasible, providing excellent
      target volume coverage, dose homogeneity, and normal tissue sparing.
      Hypofractionated proton radiotherapy in this setting merits Phase I clinical
      trial investigation.

PMID- 17544600
TI  - Impact of external beam adjuvant radiotherapy on health-related quality of life
      for long-term survivors of endometrial adenocarcinoma: a population-based study.
AB  - PURPOSE: To compare the health-related quality of life (HRQOL) among 5-10-year
      survivors of Stage I-II endometrial (adeno-)carcinoma (EC) treated with surgery
      alone or surgery with external beam adjuvant radiotherapy (EBRT) and an age
      matched norm population. METHODS AND MATERIALS: A population-based, cross
      sectional survey was conducted by the Eindhoven Cancer Registry. All patients
      were included who had been diagnosed with EC between 1994 and 1998 (n = 462).
      Information from the questionnaires returned was linked to data from the
      Eindhoven Cancer Registry on patient, tumor, and treatment characteristics.
      RESULTS: Responses were received from 75% of the patients. The analyses were
      restricted to women with Stage I-II disease at diagnosis, treated with either
      surgery alone or surgery with adjuvant EBRT, and without recurrent disease or new
      primary malignancies (n = 264). The patients who had received adjuvant EBRT (n =
      80) had had a significantly higher tumor stage and grade at diagnosis (p <
      0.0001) and a longer mean time since diagnosis (p = 0.04). Age, number of
      comorbid diseases, current marital status, nulliparity, education, and occupation
      were similar for both treatment groups. On multivariate analyses, adjuvant EBRT
      was independently and negatively associated with the vitality and physical and
      social well-being scale scores. The HRQOL scores of both treatment groups,
      however, were similar to those of an age-matched norm population. CONCLUSION: In
      general, the HRQOL of EC survivors is good. EC survivors treated with surgery
      alone had a better HRQOL than women treated with surgery and adjuvant EBRT,
      although for both groups, the HRQOL was in the range of the norm population.

PMID- 17544601
TI  - Hypofractionated intensity-modulated radiotherapy (70 Gy at 2.5 Gy per fraction)
      for localized prostate cancer: Cleveland Clinic experience.
AB  - PURPOSE: To study the outcomes in patients treated for localized prostate cancer
      with 70 Gy delivered at 2.5-Gy/fraction within 5 weeks. METHODS AND MATERIALS:
      The study sample included all 770 consecutive patients with localized prostate
      cancer treated with hypofractionated intensity-modulated radiotherapy at the
      Cleveland Clinic between 1998 and 2005. The median follow-up was 45 months
      (maximum, 86). Both the American Society for Therapeutic Radiology and Oncology
      (ASTRO) biochemical failure definition and the alternate nadir + 2 ng/mL
      definition were used. RESULTS: The overall 5-year ASTRO biochemical relapse-free
      survival rate was 82% (95% confidence interval, 79-85%), and the 5-year nadir + 2
      ng/mL rate was 83% (95% confidence interval, 79-86%). For patients with low-risk,
      intermediate-risk, and high-risk disease, the 5-year ASTRO rate was 95%, 85%, and
      68%, respectively. The 5-year nadir + 2 ng/mL rate for patients with low-,
      intermediate-, and high-risk disease was 94%, 83%, and 72%, respectively. The
      Radiation Therapy Oncology Group acute rectal toxicity scores were 0 in 51%, 1 in
      40%, and 2 in 9% of patients. The acute urinary toxicity scores were 0 in 33%, 1
      in 48%, 2 in 18%, and 3 in 1% of patients. The late rectal toxicity scores were 0
      in 89.6%, 1 in 5.9%, 2 in 3.1%, 3 in 1.3%, and 4 in 0.1% (1 patient). The late
      urinary toxicity scores were 0 in 90.5%, 1 in 4.3%, 2 in 5.1%, and 3 in 0.1% (1
      patient). CONCLUSION: The outcomes after high-dose hypofractionation were
      acceptable in the entire cohort of patients treated with the schedule of 70 at
      2.5 Gy/fraction.

PMID- 17544602
TI  - Conserved features of imprinted differentially methylated domains.
AB  - Genomic imprinting is a conserved epigenetic phenomenon in eutherian mammals,
      with regards both to the genes that are imprinted and the mechanism underlying
      the expression of just one of the parental alleles. Epigenetic modifications of
      alleles of imprinted genes are established during oogenesis and spermatogenesis,
      and these modifications are then inherited. Differentially methylated domains
      (DMDs) of imprinted genes are the genomic sites of these inherited epigenetic
      imprints. We previously showed that CpG-rich imperfect tandem direct repeats
      within three different mouse DMDs (Snurf/Snrpn, Kcnq1 and Igf2r), each with a
      unique sequence, play a central role in maintaining the differential methylation.
      This finding implicates repeat-related DNA structure, not sequence, in the
      imprinting mechanism. To better define the important features of this signal, we
      compared sequences of these three DMD tandem repeats among mammalian species. All
      DMD repeats contain short indirect repeats, many of which are organized into
      larger unit repeats. Even though the larger repeat units undergo deletion and
      addition during evolution (most likely through unequal crossovers during
      meiosis), the size of DMD tandem repeated regions has remained remarkably stable
      during mammalian evolution. Moreover, all three DMD tandem repeats have a high
      CpG content, an ordered arrangement of CpG dinucleotides, and similar predicted
      secondary structures. These observations suggest that a structural feature or
      features of these DMD tandem repeats is the conserved DMD imprinting signal.

PMID- 17544603
TI  - Comparative analysis of predicted gene expression among deep-sea genomes.
AB  - Deep-sea species live in an environment that is specifically characterized by
      extreme temperature and hydrostatic pressure. In this work, predicted highly
      expressed (PHX) genes are comparatively analyzed for six deep-sea microbes, which
      allows us to pinpoint the common highly expressed genes shared by them. The
      relationships between gene expression level and some basic properties such as
      genomic G + C content, optimal growth temperature (OGT), and environmental
      hydrostatic pressure of the six deep-sea species are also investigated. We find
      that the percentage of PHX genes out of a whole genome positively correlates to
      OGT for the deep-sea genomes, whereas such positive correlation seems not to
      exist between environmental hydrostatic pressure and percentage of PHX genes.
      Moreover, there exists a negative correlation between genomic G + C content and
      diversity of gene expression level for the deep-sea genomes, which is in sharp
      contrast to land-living microbes. We report the top 20 PHX genes for the six deep
      sea genomes and find no common highly expressed genes shared by them except for
      ribosomal proteins, transcription factors, and translation factors. Our present
      work proffers a paradigm for studying the relationship between environmental
      factors and microbes' predicted gene expression level.

PMID- 17544604
TI  - On the transfer of the Fusarium toxins deoxynivalenol (DON) and zearalenone (ZON)
      from sows to their fetuses during days 35-70 of gestation.
AB  - Eleven pregnant sows with a body weight between 153 and 197 kg were fed a control
      diet (CON, 0.15 mg DON and 0.0035 mg ZON/kg diet) or a diet containing 15% of
      Fusarium toxin contaminated triticale (MYCO, 4.42 mg DON and 0.048 mg ZON/kg
      diet) in the period of day 35 and 70 of gestation. The indirect effect of feed
      intake was separated from the direct effects of the Fusarium toxins by the
      restricted feeding regimen where all sows were fed the same amount of feed (2000
      g/d) over the whole study. At the end of experiment, fetuses were delivered by
      Caesarian section and samples of serum, bile, urine, liver, kidney and spleen of
      euthanatized sows and fetuses were taken to analyze the concentrations of DON,
      ZON and their metabolites. Feeding the Fusarium toxin contaminated diet to
      pregnant sows caused neither adverse effects on performance, organ weights and
      maintenance of pregnancy of sows nor on fetus weight and length. Furthermore, no
      teratogenic or embryolethal effects could be observed in the MYCO group.
      Hematological and clinical-chemical parameters of sows and fetuses were not
      affected by feeding, with the exception of significantly lower GLDH (glutamate
      dehydrogenase) serum activities in MYCO sows. The carry over of DON and ZON from
      the diet to the sow or fetus tissues was calculated by the diet ratio (sum of
      concentrations of all metabolites in the physiological specimen divided by the
      dietary toxin concentration), while the fetus ratio was evaluated by the sum of
      concentrations of all metabolites in the physiological specimen of the fetus
      divided by that of the sows. DON and deepoxy-DON were found in urine, bile,
      serum, liver, kidney and spleen of sows of the MYCO group, but not in the bile of
      fetuses (spleen not analyzed). ZON and its metabolite alpha-zearalenol (alpha
      ZOL) were detected in urine and bile of sows, while all specimens of fetuses as
      well as serum and liver of sows were negative for ZON metabolites. The maximum
      diet ratios for urine and bile in sows of the MYCO group were 0.84 and 0.05 for
      DON metabolites and 1.2 and 3.8 for ZON metabolites, underscoring the differences
      in metabolism and excretion of both toxins. The maximum diet ratio of DON and
      deepoxy-DON into liver, kidney and spleen of MYCO sows were 0.003, 0.007 and
      0.003, respectively. The maximum fetus ratio of DON and deepoxy-DON into urine,
      bile, serum, liver and kidney of fetuses were 0.006, 0, 0.5, 0.88, and 0.33,
      while the maximum placental ratio (sum of toxin concentrations in the
      physiological specimen of the fetus divided by the toxin serum concentration of
      the sow) were 0.64, 0, 0.50, 0.70 and 0.52, respectively. Therefore, it can be
      concluded that the developing fetus is exposed to DON between the gestation days
      35 and 70 when the sows are fed a Fusarium toxin contaminated diet. ZON
      concentration in the MYCO diet was too low to get reliable results for fetus or
      placental ratios.

PMID- 17544605
TI  - Ultrasonographic fetometry and determination of fetal sex in buffaloes (Bubalus
      bubalis).
AB  - The aim of the current study was to establish ultrasonic biometric threshold of
      different fetal parts in buffaloes and to evaluate the feasibility and accuracy
      of ultrasonic fetal sex determination. Serial ultrasonographic examinations were
      carried out on twelve pregnant buffalo-cows, during which fetal parts were
      measured, and fetal sex and presentation were determined. The obtained results
      revealed that embryo and amniotic vesicle (AV) were detected by the forth and
      fifth week of pregnancy, respectively. Organization was observed by the seventh
      week, while ossification was indicated between the eighth and 10th week. High
      correlations were found between different studied parameters and gestational age,
      where the highest correlation was found with the crown-rump length (CRL) and
      amniotic vesicle diameter (AVD) at the early-gestation; the biparietal diameter
      (BPD) at the mid-gestation; and the eyeball diameter (EBD) at the mid- and late
      gestation. The results also revealed that the best window for fetal sexing was
      found between the 10th and 18th week of gestations, with an overall accuracy of
      97.1%. The final polarity with all fetuses in anterior presentation was adopted
      by the 30th week. In conclusion, the overall data indicated the feasibility and
      value of ultrasonographic fetometry in buffaloes for evaluation of fetal
      development, estimation of gestational age and determination of fetal sex.

PMID- 17544606
TI  - Synthesis and in vitro evaluation of thiolated hyaluronic acid for mucoadhesive
      drug delivery.
AB  - It was the aim of this study to synthesize and characterize a novel hyaluronic
      acid-cysteine ethyl ester (HA-Cys) conjugate providing improved mucoadhesive
      properties and a significantly lowered biodegradation rate. Mediated by
      carbodiimide and N-hydroxysuccinimide, L-cysteine ethyl ester hydrochloride was
      covalently attached to hyaluronic acid (HA, hyaluronan) via the formation of an
      amide bond. The adhesive properties of HA-Cys conjugates were evaluated in vitro
      on a freshly excised porcine mucosa via the rotating cylinder method. The
      cohesive properties of the resulting conjugates were evaluated by oxidation
      experiments. Biodegradability studies were carried out by viscosity measurements
      and spectrophotometric assays. Release studies were performed with fluorescein
      isothiocyanate-dextrans (FD) as model compounds. The obtained conjugate displayed
      201.3+/-18.7 micromol immobilized free thiol groups and 85.7+/-22.3 micromol
      disulfide bonds per gram polymer. Results from the rotating cylinder method
      showed more than 6.5-fold increase in the adhesion time of HA-Cys versus
      unmodified HA. In aqueous solutions, the obtained conjugate demonstrated improved
      cohesive properties. The hydrolysis degree of HA-Cys was lower compared with the
      corresponding unmodified HA in the framework of viscosity experiments. In
      addition, the cross-linking process via disulfide bonds additionally reduced the
      rate of degradation of the new derivative. Cumulative release studies out of
      matrix tablets comprising HA-Cys and the model compound FD demonstrated a
      sustained drug release for more than 12h due to in situ formation of inter- and
      intramolecular disulfide bonds in the thiomer matrix. According to the results of
      the present study, this novel thiolated polymer seems to represent a promising
      multifunctional excipient for the development of various drug delivery systems.

PMID- 17544607
TI  - Benign infantile convulsions associated with mild gastroenteritis: a
      retrospective study of 39 cases including virological tests and efficacy of
      anticonvulsants.
AB  - Benign convulsions associated with mild gastroenteritis (CwG) are a commonly
      observed disorder in Asia, especially in infants and seniors. Here, we describe a
      retrospective study about the clinical features of CwG in 62 children
      hospitalized at St. Mary's Hospital (Kurume City, Japan) between January 1, 2000
      and March 31, 2006, and further evaluate the efficacies of various anticonvulsant
      treatments for patients with CwG due to either rotavirus or norovirus. Causative
      diarrheal viruses were detected in 71% of the fecal specimens tested; 30 patients
      were positive for rotavirus, nine patients were positive for norovirus, two
      patients were positive for sapovirus, two patients were positive for adenovirus,
      and one patient was positive for coxackievirus A4. The age of onset for patients
      with norovirus-positive CwG (16.7+/-2.7 months) was significantly lower than that
      of patients with rotavirus-positive CwG (23.0+/-8.7 months). The duration of the
      seizures due to norovirus infection (11.8+/-12.0 h) was significantly longer than
      that due to rotavirus infection (4.9+/-5.7 h). There were no significant
      differences between the two groups with regard to the results of blood chemistry
      analysis, including the concentrations of serum electrolytes, blood glucose
      levels, and liver function tests. In this preliminary study, the duration of
      seizures in patients with CwG due to norovirus that was treated with
      carbamazepine was significantly shorter than the duration of seizures in the
      patients treated with another anticonvulsant (phenobarbital). Further randomized
      controlled studies are required to clarify the efficacies of the various
      anticonvulsants for patients with CwG.

PMID- 17544608
TI  - ADC measurements at low and high b values: insight into normal brain structure
      with clinical DWI.
AB  - PURPOSE: To demonstrate drop in brain ADC measurements from low to high b values;
      to evaluate the structural information provided based on those changes; and to
      discuss the anatomical reasons for ADC differences. METHODS: Four cerebral ROI
      (precuneus-PRC, hippocampus-HIP, and the genu-GCC and splenium-SCC of the corpus
      callosum-CC) were drawn for ADC measurements with low (1000) and high (3000) b
      value DWI in 50 normal subjects. ANOVA and Bonferroni correction tested ADC
      differences between areas, between both hemispheres, between GCC and SCC, and
      between b-value related ADC drop within areas. Pearson test evaluated dependence
      of interhemispheric and intercallosum ADC measurements obtained with the same b
      value, dependence between areas of intrazonal drop, and the interhemispheric and
      intercallosum dependence of intrazonal drop. RESULTS: ADCs differed between areas
      (P<.0001). Interhemispheric ADC only differed in PRC with low b-value (P<.027).
      No HIP asymmetries occurred regardless the b-value. ADC drop within PRC and HIP
      was similar but differed (P<.0001) from ADC drop within both CC ROI. ADC drop was
      also different between GCC and SCC (P<.0001). In PRC and HIP, ADC showed a
      significant interhemispheric and intrazonal dependence (P<.0001). There was no
      GCC to SCC ADC dependence. Intrazonal dependence in the CC was only significant
      in the SCC (P<.001). Interhemispheric dependence of intrazonal drop was
      significant (PRC P=.007; HIP P<.0001) but failed to reach significance in the CC.
      CONCLUSION: Low and high b-value measurements show different diffusion behaviours
      within different tissues, especially in a highly anisotropic structure as the
      corpus callosum. This fact can provide valuable information about brain structure
      and different diffusion compartments in clinical DWI.

PMID- 17544609
TI  - Validation of rapid and simple LC-MS/MS method for determination of voriconazole
      in rat plasma.
AB  - A rapid, simple and sensitive LC-MS/MS analytical method was developed and
      validated for the determination of voriconazole (VRC) in rat plasma, using
      ketoconazole as internal standard (IS). Analysis was performed on a Shimadzu HPLC
      system using a Shimadzu C18 column and isocratic elution with acetonitrile-water
      formic acid (60:40:0.05, v/v/v), at a flow of 1.0 mL/min (split ratio 1:5), and a
      mass spectrometer Micromass, equipped with a double quadrupole and an
      electrospray ionization interface, operated in a positive mode. Plasma samples
      were deproteinized with methanol (1:2) and 30 microL of the supernatant was
      injected into the system. The retention times of VRC and IS were approximately
      3.3 and 2.7 min, respectively. Calibration curves in spiked plasma were linear
      over the concentration range of 50-2500 ng/mL with determination coefficient
      >0.98. The lower limit of quantification was 50 ng/mL. The accuracy of the method
      was within 5%. Intra- and inter-day relative standard deviations were less or
      equal to 12.5 and 7.7%, respectively. The applicability of the LC-MS-MS method
      for pharmacokinetic studies was tested using plasma samples obtained after
      intravenous administration of VRC to male Wistar rats. The reported method
      provided the necessary sensitivity, linearity, precision, accuracy, and
      specificity to allow the determination of VRC in pre-clinical pharmacokinetic
      studies.

PMID- 17544610
TI  - Changes in brachial-ankle pulse wave velocity in subclinical hypothyroidism
      during normalization of thyroid function.
AB  - OBJECTIVE: Subclinical hypothyroidism affects 5-15% of the population and is
      associated with increased cardiovascular morbidity, although this is
      controversial. We recently reported a significant increase in brachial-ankle
      pulse wave velocity (baPWV), a parameter of arterial stiffening and an
      independent predictor for cardiovascular events, in subclinical hypothyroidism.
      The current study was performed to assess changes in enhanced baPWV in
      subclinical hypothyroidism during normalization of thyroid function. METHODS:
      Forty-two subclinical hypothyroid patients (male/female ratio 8/34) were
      monitored for changes in baPWV before and after levothyroxine (L-T(4))
      replacement therapy. RESULTS: After attaining euthyroidism, 59.5% and 40.5% of
      the patients showed reduction and increase of baPWV, respectively. Baseline baPWV
      and pulse pressure were significantly higher in patients with reduced baPWV
      (1940.3+/-126.4 vs. 1726.4+/-110.4 cm/s, P=0.046; 62.1+/-3.1 vs. 50.7+/-3.7 mmHg,
      P=0.026, respectively). Baseline baPWV was significantly correlated with baseline
      pulse pressure in both groups, but the change in baPWV was significantly
      correlated with baseline pulse pressure only in patients with reduced baPWV (rho=
      0.522, P=0.046). The male/female ratio was significantly lower in patients with
      reduced baPWV (4/21 vs. 7/10), and systolic, diastolic and pulse pressures and
      pulse rate decreased significantly only in patients with reduced baPWV.
      CONCLUSIONS: Our results suggest that L-T(4) replacement therapy may be
      especially beneficial in female subclinical hypothyroid patients with high
      baseline baPWV and pulse pressure. The beneficial effects of L-T(4) replacement
      therapy in decreasing arterial stiffening and thus preventing cardiovascular
      disease might be limited to this sub-population.

PMID- 17544612
TI  - [Screening for hereditary HFE hemochromatosis].
AB  - Screening for hereditary HFE hemochromatosis in the general population, by either
      phenotype or genotype, is not currently recommended by the French High Health
      Authority. Targeted screening for hereditary HFE hemochromatosis in groups with
      specific diseases (people with asthenia, arthropathic disorders, liver or heart
      disease, etc.) has not been shown to be effective. Family screening in first
      degree relatives of any proband homozygous for C282Y is strongly advised. This
      should involve both phenotypic screening, that is, testing for serum iron markers
      and, if possible, a genotype study of siblings and adult children, conducted
      according to the rules for genetic counseling and testing. This type of screening
      is cost-effective. One obstacle today is that the national health insurance fund
      does not reimburse the HFE test.

PMID- 17544611
TI  - [Management of fungal urinary tract infections].
AB  - Fungal urinary tract infections (funguria) are rare in community medicine, but
      common in hospitals where 10 to 30% of urine cultures isolate Candida species.
      Clinical features vary from asymptomatic urinary tract colonization (the most
      common situation) to cystitis, pyelonephritis, or even severe sepsis with
      fungemia. The pathologic nature of funguria is closely related to host factors,
      and management depends mainly on the patient's underlying health status.
      Microbiological diagnosis of funguria is usually based on a fungal concentration
      of more than 10(3)/mm(3) in urine. No cutoff point has been defined for leukocyte
      concentration in urine. Candida albicans is the most commonly isolated species,
      but previous antifungal treatment and previous hospitalization affect both
      species and susceptibility to antifungal agents. Treatment is recommended only
      when funguria is symptomatic or in cases of fungal colonization when host factors
      increase the risk of fungemia. The antifungal agents used for funguria are mainly
      fluconazole and amphotericin B deoxycholate, because other drugs have extremely
      low concentrations in urine. Primary and secondary preventions are essential. The
      reduction of risk factors requires removing urinary catheters, limiting
      antibiotic treatment, and optimizing diabetes mellitus treatment.

PMID- 17544614
TI  - Frameworks for prescribing in comorbid illness.

PMID- 17544613
TI  - [Current and upcoming treatments for Behcet disease].
AB  - Behcet disease is a multisystem inflammatory disorder, the cause of which remains
      unclear. Vasculitis is its predominant histopathological feature. It remains a
      source of significant morbidity in affected patients, many of whom become blind.
      Treatment of its various manifestations remains controversial today because of
      the paucity of randomized controlled trials and the absence of standardized
      outcome measures for this disease. The preferred treatment modalities combine
      different drugs, including topical therapies as well as systemic corticosteroids,
      NSAIDs, colchicine, and immunosuppressive and cytotoxic agents. The principal
      objectives are always relief of symptoms, control of inflammatory eye disease,
      suppression of systemic inflammation and vasculitis and prevention of recurrences
      and thus of irreversible damage. Although the prognosis of various manifestations
      of Behcet disease has improved, many patients still have refractory disease that
      requires treatment with combinations of various immunosuppressants, cytotoxic
      agents, and corticosteroids, which may lead to serious infections or secondary
      malignancy. Recent improvements in our understanding of the pathogenic mechanisms
      of Behcet disease, especially its molecular basis, have led to a new generation
      of potential treatments with improved side-effect profiles and more specific
      immune targeting. These include new immunosuppressants, biologic medicines,
      tolerizing agents and immunoablation techniques. Until randomized controlled
      studies with these agents are conducted, however, no final judgment about their
      usefulness is possible.

PMID- 17544615
TI  - Some characteristics of fluoride-induced cell death in rat thymocytes:
      cytotoxicity of sodium fluoride.
AB  - Fluoride is found in the atmosphere, water, soil, coal, food, dental and
      industrial uses. There were some case reports concerning acute fluoride poisoning
      in workplaces and laboratories. However, there is limited information concerning
      the mechanism of fluoride-induced cell death. To study the cytotoxicity of
      fluoride, the effect of sodium fluoride (NaF) on rat thymocytes has been examined
      by using a flow cytometer with appropriate fluorescence probes for membrane and
      cellular parameters. The cytotoxicity of NaF under nominal Ca2+-free condition
      was significantly lower than that under control condition. NaF also increased
      intracellular Ca2+ concentration. NaF significantly increased the population of
      shrunken cells and the cells positive to annexin V. Both are known to be
      parameters for early stage of apoptosis. However, NaF decreased the population of
      cells with hypodiploidal DNA, indicating that NaF apparently attenuated
      spontaneous apoptosis in rat thymocytes. It may be suggested that NaF induces
      necrosis, associated with some apoptotic characteristics.

PMID- 17544616
TI  - A cytotoxin isolated from Agkistrodon acutus snake venom induces apoptosis via
      Fas pathway in A549 cells.
AB  - ACTX-6 is a protein isolated from Agkistrodon acutus snake venom and demonstrated
      cytotoxic activity to various cancer cells in vitro. In this paper the exact
      mechanism in ACTX-6-induced cell death was investigated and it was found that
      ACTX-6 could induce cell apoptosis. The results of Western blot and RT-PCR showed
      that ACTX-6 could induce Fas and FasL protein expression. When Fas signaling
      pathway was blocked by neutralizing antibodies to Fas or FasL, ACTX-6-induced
      apoptosis was inhibited. DISC formation was also detected by immunoprecipitation.
      These results suggested that Fas pathway was involved in ACTX-6-induced
      apoptosis. The activities of caspase-3, 8 and 9 were assayed and the activation
      of caspase-9 demonstrated that mitochondrial pathway was also involved in ACTX-6
      induced apoptosis. Bid cleavage and dissipation of mitochondrial membrane
      potential (delta psi(m)) verified the involvement of mitochondria. ACTX-6 is an L
      amino acid oxidase and can oxidize L-amino acid to generate hydrogen peroxide.
      The production of ROS in ACTX-6-treated cells was detected and the ROS scavenger
      catalase could inhibit ACTX-6-induced apoptosis. Western blot analysis showed
      that JNK was phosphorylated in ACTX-6-treated cells and c-Jun was also activated.
      JNK inhibitor SP600125 could inhibit ACTX-6-induced apoptosis and catalase could
      inhibit JNK and c-Jun phosphorylation. It could be concluded that JNK pathway was
      necessary in ACTX-6-induced apoptosis and the oxidative stress generated by ACTX
      6 was responsible for the activation of JNK.

PMID- 17544617
TI  - Sensory genes and mate choice: evidence that duplications, mutations, and
      adaptive evolution alter variation in mating cue genes and their receptors.
AB  - Fascinating new data, revealed through gene sequencing, comparative genomics, and
      genetic engineering, precisely establish which genes are involved in mate choice
      and mating activity--behaviors that are surprisingly understudied from a genetic
      perspective. Discussed here are some of the recently identified visual and
      chemosensory genes that are involved in mate choice and mating behavior. These
      genes' products are involved in the production, transmission, and receipt of
      crucial sensory mate-choice cues that affect fitness. This review exposes
      newfound evidence that alternative splicing, gene-expression pattern changes, and
      molecular genetic variation in sensory genes are crucial for both intra- and
      interspecific mate choice and mating success. Many sensory genes have arisen
      through gene duplications, and data amassed from studies conducted at scales
      ranging from individual genes to genomic comparisons show that strong, positive
      Darwinian selection acts on several mating-related genes and that these genes
      evolve rapidly.

PMID- 17544618
TI  - Characterization of 5' untranslated regions of the voltage-gated sodium channels
      SCN1A, SCN2A, and SCN3A and identification of cis-conserved noncoding sequences.
AB  - The human voltage-gated sodium channel gene cluster on chromosome 2q24 contains
      three paralogs, SCN1A, SCN2A, and SCN3A, which are expressed in the central
      nervous system. Mutations in SCN1A and SCN2A cause several subtypes of idiopathic
      epilepsy. Furthermore, many SCN1A mutations are predicted to reduce protein
      levels, emphasizing the importance of precise sodium channel gene regulation. To
      investigate the genetic factors that regulate the expression of SCN1A, SCN2A, and
      SCN3A, we characterized the 5' untranslated region of each gene. We identified
      multiple noncoding exons and observed brain region differences in the expression
      levels of noncoding exons. Comparative sequence analysis revealed 33 conserved
      noncoding sequences (CNSs) between the orthologous mammalian genes and 6 CNSs
      between the three human paralogs. Seven CNSs corresponded to noncoding exons.
      Twelve CNSs were evaluated for their ability to alter the transcription of a
      luciferase reporter gene, and 3 resulted in a modest, but statistically
      significant change.

PMID- 17544619
TI  - Adverse reproductive effects of beer drinking.
AB  - This short communication represents a systematic review of the literature about
      beer drinking during gestation. A Medline search was undertaken of articles based
      on the criterion that beer and pregnancy were in the abstract and central to the
      article. Manuscripts were to be published in English in peer review medical
      journals from 1981 to 2006. Beer is a commonly consumed alcoholic beverage among
      reproductive-age adults. Beer drinking males have an increased risk of
      contributing to pregnancy waste. Women consume beer before and after pregnancy
      recognition. Binge drinking appears to be a common drinking behavior, and those
      who binge drink have an increased risk of impaired fetal growth and offspring
      behavior. Beer consumption by lactating women might temporarily impair motor
      function of nursing infants. Evidence for potentiation of beer effects by
      congeners and by simultaneous use of substances of abuse is inconclusive.

PMID- 17544620
TI  - Differentiation of three species of ixodid tick, Dermacentor andersoni, D.
      variabilis and D. albipictus, by PCR-based approaches using markers in ribosomal
      DNA.
AB  - Three species of Dermacentor, Dermacentor albipictus, Dermacentor andersoni and
      Dermacentor variabilis, commonly occur in Canada. D. andersoni and D. variabilis
      are morphologically similar and are important vectors of human and animal
      pathogens. A practical polymerase chain reaction (PCR) assay, based on the
      amplification of part of the second internal transcribed spacer ribosomal DNA
      (pITS-2 rDNA), was developed to distinguish D. andersoni from D. variabilis. In
      addition, single-strand conformation polymorphism (SSCP) analysis of the pITS-2
      rDNA provided a reliable method of distinguishing specimens of the three species
      of ixodid tick. PCR and pITS-2 SSCP were also used to determine whether there was
      hybridization between D. andersoni and D. variabilis at two localities in
      Saskatchewan where they occur in sympatry. These molecular tools will be useful
      for the unequivocal identification of D. andersoni and D. variabilis at all life
      cycle stages, which is essential for studies on their ecology and on the
      transmission of tick-borne diseases. Also, pITS-2 SSCP may be of potential use
      for discriminating among the other morphologically similar species within the
      genus Dermacentor.

PMID- 17544621
TI  - Oxidative stress-induced apoptosis of bile duct cells in primary biliary
      cirrhosis.
AB  - There has been a relative paucity of effort at defining effector mechanisms of
      biliary damage in PBC. We hypothesize that biliary cells are destroyed secondary
      to the immunologic relationships of inflammation and biliary epithelial apoptosis
      and, in particular, that biliary damage is a result of reduced levels of
      glutathione-S-transferase (GST), the production of hypochlorous acid (HOCl) and
      its association with eosinophil peroxidase (EPO). To address this issue, we
      examined the expression of EPO and GST in PBC and control livers and demonstrated
      an increase of EPO within the portal areas of PBC. We also demonstrated that
      macrophages have evidence of phagocytosed EPO. Furthermore, we studied the
      influence of HOCl on apoptosis in cultured human biliary epithelial cells (BEC)
      as well as the associated activity of Bcl-2, Bax, p-JNK, JNK, p53, Fas and
      caspase-3. HOC1-induced apoptosis in BEC in a dose-dependent fashion increased
      the activity of caspase-3 and the expression of p53 and p-JNK. Pretreatment with
      l-buthionine-(S,R)-sulfoximine, a glutathione (GSH) inhibitor, potentiated the
      sensitivity of BEC to HOCl-induced apoptosis. We conclude that intracellular GSH
      reduction leads directly to BEC apoptosis. Modulation of these events will be
      critical to reduce immune-mediated destruction.

PMID- 17544622
TI  - Coactivation of Toll-like receptor-3 and -7 in immune complex glomerulonephritis.
AB  - The molecular mechanisms of viral infection-induced glomerulonephritis are poorly
      understood. Toll-like receptor (TLR)-3 and TLR7 recognize viral RNA and their
      exposure to TLR3 or TLR7 can trigger the exacerbation of established immune
      complex disease in MRLlpr mice. Because coactivation of TLR3 and TLR7 was shown
      to synergistically activate dendritic cells in vitro, we hypothesized that
      simultaneous ligation of TLR3 and TLR7 would elicit additive effects on the
      exacerbation of glomerulonephritis in MRLlpr mice. Saline, 50 microg pI:C RNA, 25
      microg of the TLR7 agonist imiquimod, or a combination of both were injected
      every other day to MRLlpr mice from week 16-18 of age. Coinjection of pI:C RNA
      and imiquimod had no synergistic effect on serum levels of IL-6 and IL12p70,
      dsDNA autoantibody levels, and glomerulonephritis. This was consistent with a
      lack of synergistic effects on cytokine release of TNF- and IFNgamma
      prestimulated monocytes in vitro. Furthermore, in glomerular mesangial cells a
      synergistic effect of pI:C RNA and imiquimod was generally absent due to the lack
      of TLR7 expression. We conclude that a number of mechanisms protect the host from
      additive effects of TLR3-TLR7 coactivation on renal pathology in vivo.

PMID- 17544624
TI  - Quo vadis pediatric nuclear medicine.
AB  - What has happened to the nuclear medicine subspecialty since those earlier issues
      of the Seminars in Nuclear Medicine? The earliest issues in 1972 presented topics
      in vogue at the time that included brain "scanning," cisternography, whole body
      counting, and abdominal imaging with (99m)Tc pertechnetate. The second pediatric
      subspecialty issues in 1993 reflected a 21-year evolution of the subspecialty and
      included the topics of renal scintigraphy, labeled cells for abdominal imaging,
      metaiodobenzylguanidine imaging, single photon emission computed tomography, and
      bone scintigraphy for benign disorders. The current issues will address diverse
      topics that cover the spectrum of the current practice of pediatric nuclear
      medicine. They include radiation exposure and absorbed dose reduction, positron
      emission tomography/computed tomography in children, neuroblastoma and other
      neuroendocrine tumors, thyroid cancer and therapy, bone density studies and, of
      course, the most prevalent studies in children, renal and bone. Brain, heart, and
      lung studies complete the spectrum.

PMID- 17544625
TI  - Antenatally detected hydronephrosis.
AB  - The strategy of management of children with hydronephrosis has considerably
      changed as a result of the development of ultrasound techniques, allowing a
      prenatal detection. Hydronephrosis is defined as a dilation of the renal
      collecting system, and several entirely different clinical entities can be
      considered this general heading, whereas early detection may have a different
      impact depending on the entity considered. The present work aims to describe a
      certain number of these clinical entities, to discuss the strategic options of
      management that are proposed, and to evaluate the role of medical imaging, in
      particular the radionuclide approach. Congenital ureteropelvic junction anomaly,
      vesicoureteral reflux, posterior urethral valves, and duplex kidney will be
      successively considered. Multicystic dysplastic kidney disease, although not
      classified as hydronephrosis, will be mentioned because it may be mistaken for
      hydronephrosis.

PMID- 17544626
TI  - Renal infection and vesico-ureteric reflux.
AB  - Urinary tract infection (UTI) is a common disease of childhood. The investigation
      of UTI in children has been the subject of debate and controversy for many years.
      Most workers agree that the first imaging modality to be used should be an
      ultrasound examination to exclude obstruction, structural abnormalities, and
      renal calculi. The role of (99m)Tc dimercaptosuccinic acid scintigraphy (DMSA) in
      the diagnosis of acute pyelonephritis is becoming increasingly important. Many
      argue that if the DMSA study is normal at the time of acute UTI, no further
      investigation is required because the kidneys have not been involved and thus
      there will be no late sequelae. Others use the acute DMSA study to determine the
      intensity of antibiotic therapy. The importance of the role of vesico-ureteric
      reflux (VUR) is being debated. Some workers will only proceed to cystography to
      detect VUR if the DMSA study is abnormal, whereas others advocate a more
      aggressive approach. VUR can be identified by a variety of radiological and
      scintigraphic techniques. Although the radiological cystogram is the gold
      standard and is essential in the first UTI in a male patient, to exclude the
      presence of posterior urethral valves, radionuclide cystograms are advantageous
      in other situations. Suprapubic cystography techniques have been described to
      overcome the trauma of urethral catheterization but have not been widely
      accepted.

PMID- 17544627
TI  - Pediatric gastrointestinal nuclear medicine.
AB  - General localization of gastrointestinal bleeding through the use of labeled red
      blood cells may be performed in children, or (99m)Tc-pertechnetate may be used if
      a Meckel's diverticulum is suspected. As in adults, cholecystitis and biliary
      leak may be assessed in children via (99m)Tc-IDA derivatives. Gastroesophageal
      reflux can be evaluated by oral consumption of the child's usual diet labeled
      with (99m)Tc sulfur colloid. For the scintigraphic determination of pulmonary
      aspiration, a relatively high concentration of tracer within a drop of liquid is
      placed beneath the child's tongue followed by dynamic imaging of the respiratory
      tract. Colonic transit scintigraphy can aid in the identification and therapeutic
      decision-making in patients with functional fecal retention, the most common
      cause of chronic constipation in children. (18)F-DOPA positron emission
      tomography is useful for classifying pancreatic involvement in infantile
      hyperinsulinism as focal or diffuse, thereby differentiating between patients who
      should receive curative focal pancreatic resection versus those who should
      receive medical management. Assessment of protein-losing enteropathy can be
      conducted scintigraphically and, compared with fecal alpha-1 antitrypsin
      collection, the scintigraphic method can detect esophageal and gastric protein
      loss. Also, scintigraphic quantification of protein loss can be performed without
      the requirement for fecal collection. Intestinal inflammation in children with
      inflammatory bowel disease can be evaluated using (99m)Tc white blood cells. The
      scintigraphic method is safe, accurate, well-tolerated by children and
      complementary to endoscopy in most patients.

PMID- 17544628
TI  - Neuroblastoma and other neuroendocrine tumors.
AB  - Neuroblastoma is the most common extracranial solid tumor of childhood. It
      commonly presents in children younger than 2 years of age, with 90% being younger
      than 5 years of age. There is marked variability in clinical behavior ranging
      from spontaneous regression or differentiation into benign tumors to rapid and
      progressive fatal disease. Approximately 50% of patients will have metastases at
      presentation. The management is dependent on age, stage of disease, and
      biological and biochemical markers. Nuclear medicine plays an important role in
      the initial staging, as a prognostic indicator, for assessment of response to
      treatment, and also in therapy. The most common nuclear medicine diagnostic
      studies are (99m)Tc-disphosphonate bone scintigraphy and (123)I-MIBG
      (metaiodobenzylguanidine) scintigraphy. Bone scintigraphy has been the main
      investigational modality to diagnose skeletal metastases. Whole body imaging with
      (123)I-MIBG has become the preferred diagnostic test because this agent
      accumulates in neuroblastoma in 90% to 95% of cases and will accumulate in the
      primary tumor and metastases particularly in bone, bone marrow, lymph nodes, and
      soft tissues. MIBG can be used to assess therapy response and is a significant
      prognostic indicator. Other diagnostic techniques include positron emission
      tomography (PET)/computed tomography, mainly using (18)F-fluorodeoxyglucose.
      Other more experimental PET agents, as well as radiolabeled antibodies and
      octreotide, also are being investigated. Therapy has mainly focused on palliation
      and has been used alone or in combination with chemotherapy in high-risk
      refractory or relapsed patients. Major attention is being placed on
      stratification of patients to try and reduce the side effects associated with
      intensive megatherapy in the low to intermediate risk patients. Neuroendocrine
      tumors (NETs) are rare in childhood, but nuclear medicine techniques, mainly
      using MIBG and somatostatin receptor agents, have a role in diagnosis, staging,
      and a limited role in therapy. Newer radiopharmaceuticals, including PET agents,
      are being evaluated for the assessment of NET. Nuclear medicine techniques play a
      major role in the management of neuroblastoma and NET.

PMID- 17544629
TI  - Pediatric dual-energy X-ray absorptiometry: technique, interpretation, and
      clinical applications.
AB  - This article reviews the dual-energy x-ray absorptiometry (DXA) technique, its
      interpretation, and clinical applications with emphasis on the considerations
      unique to pediatrics. Specifically, the use of DXA in children requires the
      radiologist to be a "clinical pathologist," monitoring the technical aspects of
      the DXA acquisition, a "statistician" knowledgeable in the concepts of Z-scores
      and least significant changes, and a "bone specialist," aware of the DXA findings
      in a large number of clinical diseases, providing the referring clinician with a
      meaningful context for the numeric result obtained with DXA.

PMID- 17544630
TI  - An fMRI investigation of procedural learning in unaffected siblings of
      individuals with schizophrenia.
AB  - Vulnerability for schizophrenia is related, in part, to genetic predisposition.
      The identification of pathophysiological abnormalities associated with the
      disorder that are also present in unaffected family members of individuals with
      schizophrenia may assist in delineating the genetic contributions to
      vulnerability for schizophrenia. Previous functional Magnetic Resonance Imaging
      (fMRI) investigations of procedural learning in patients with schizophrenia
      identified reduced activity in the frontal cortex, basal ganglia, and parietal
      cortex during performance of the serial reaction time (SRT) task suggesting that
      abnormal function of these regions may relate to genetic vulnerability for
      schizophrenia. In order to examine this hypothesis, 12 unaffected siblings of
      patients and 15 controls underwent fMRI during performance of the SRT task.
      Unaffected siblings demonstrated normal performance on the SRT task. However,
      compared to controls unaffected siblings demonstrated less activity in regions of
      the frontal and parietal lobes and, to a lesser extent, basal ganglia, during
      procedural learning. Interestingly, unaffected siblings demonstrated greater
      activity in regions of the frontal cortex during the control condition compared
      to the procedural learning condition of the SRT task, an idiosyncratic pattern
      that was also observed in patient groups but not control subjects of two prior
      imaging studies. The findings support previous investigations suggesting that
      altered cerebral neurophysiology during performance of cognitive tasks may be
      related to genetic vulnerability for schizophrenia. Identification of genes
      related to the function of cerebral regions such as the prefrontal cortex,
      parietal lobe, and basal ganglia may assist in delineating the genetic
      contributions to schizophrenia.

PMID- 17544631
TI  - Voxel-based analysis of P300 electrophysiological topography associated with
      positive and negative symptoms of schizophrenia.
AB  - Abnormal P300 waveforms of the event-related potentials during the auditory
      oddball task are one of the most consistent findings in patients with
      schizophrenia. In the present study, we sought to test the hypothesis that the
      abnormal P300 waveform results from composite representation of neural activity
      in anatomically distinct brain regions responsible for the manifestation of
      positive and negative symptoms. We used the low-resolution brain electromagnetic
      tomography (LORETA) to obtain current density images of the P300 component from
      26 patients with schizophrenia. The statistical parametric mapping (SPM) was
      applied to the LORETA images in order to identify brain regions that are related
      with the severity of psychotic symptoms as evaluated by the Brief Psychiatric
      Rating Scale (BPRS). The BPRS Total score was negatively correlated with the P300
      current density in the left superior temporal gyrus (r=-0.615, corrected p=0.009)
      and that in the right medial frontal region (r=-0.571, corrected p=0.019) by
      means of SPM single-subject covariates model. These brain regions were included
      in the region-specific P300 sources as represented by the current density maxima
      (corrected p<0.05) using SPM one-sample t-test. A subsequent region-of-interest
      analysis of Pearson correlations revealed specific relationships between the
      Positive subscale score and the mean current density in the left superior
      temporal gyrus (r=-0.528, p=0.005) and between the Negative subscale score and
      the mean current densities in the medial frontal region (r=-0.551, p=0.003) and
      left superior temporal gyrus (r=-0.499, p=0.009). These results indicate that
      functional disturbances of neural networks involving the medial prefrontal and
      superior temporal regions may be responsible for the generation of positive and
      the negative psychotic symptoms of schizophrenia.

PMID- 17544632
TI  - Impaired top-down control of visual search in schizophrenia.
AB  - This study examined top-down and bottom-up control of attention in a group of 24
      patients with schizophrenia and 16 healthy volunteers. Participants completed a
      visual search task in which they reported whether a target oval contained a gap.
      The target was accompanied by 5, 11, or 17 distractors. On some trials, the
      target was identified by a highly salient feature that was shared by only 2
      distractors, causing this feature to "pop out" from the display. This feature
      provided strong bottom-up information that could be used to direct attention to
      the target. On other trials, half of the distractors contained this feature
      making these distractors no more salient than the other distractors requiring
      greater use of top-down control to restrict processing to items containing this
      feature. Patient visual search efficiency closely approximated control
      performance in the first trial type. In contrast, patients demonstrated
      significant slowing of search in the second trial type, which required top-down
      control. These results suggest that schizophrenia does not impair the ability to
      implement the selection of a target when attention can be guided by bottom-up
      information, but it does impair the ability to use top-down control mechanisms to
      guide attention. These results extend prior studies that have focused on aspects
      of executive control in complex tasks and suggest that a similar underlying
      deficit may also impact the performance of perceptual systems.

PMID- 17544633
TI  - Premorbid behavioral and intellectual functioning in schizophrenia patients with
      poor response to treatment with antipsychotic drugs.
AB  - INTRODUCTION: Approximately one third of schizophrenia patients show partial or
      no response to pharmacotherapy. Despite intensive investigations, the
      phenomenological and biological characteristics of such patients are far from
      elucidated. This study examined the premorbid behavioral and intellectual
      functioning of schizophrenia patients who showed poor response to antipsychotic
      treatment. METHOD: One hundred twenty-nine schizophrenia patients who showed poor
      response to treatment were ascertained from a national register and matched by
      gender, age and education to 129 patients who showed adequate response. The
      groups were compared on premorbid measures of behavioral and intellectual
      functions. RESULTS: As a group, treatment-resistant male patients had
      significantly lower (worse) social functioning [p=0.002], and individual autonomy
      [p<0.0001] scores before the onset of the illness compared to treatment non
      resistant patients. Male and female treatment-resistant patients did not differ
      from non-resistant patients in premorbid intellectual functioning [p>0.1].
      CONCLUSIONS: Low premorbid social functioning and individual autonomy, but not
      intellectual functioning, could serve as predictors of poor treatment response in
      schizophrenia.

PMID- 17544634
TI  - Effects of tributyltin on the emotional behavior of C57BL/6 mice and the
      development of atopic dermatitis-like lesions in DS-Nh mice.
AB  - BACKGROUND: Tributyltin (TBT) compounds have been widely used as antifouling
      biocides on ships and are known to be endocrine disrupters. However, little is
      known about the influence of TBT on emotion and atopic dermatitis. OBJECTIVE: We
      evaluated the effects of TBT on the emotional behavior of C57BL/6 mice and on
      development of AD-like skin lesions in DS-Nh mice, which develop dermatitis
      spontaneously under conventional conditions. METHODS: Five-week-old C57BL/6 mice
      were fed 0, 50, 100, 200, 300, 400 or 500 ppm TBT diet for 2 weeks. At the end of
      the exposure period, an open-field test was performed. Six-week-old DS-Nh mice
      were fed 200 ppm TBT for 14 weeks. Skin eruption scores were checked every week.
      Skin biopsy was performed from ears. RESULTS: No significant difference was found
      in mortality or body weight among the groups receiving 0-200 ppm TBT diet during
      the course of the study. In the open-field test, mice fed 200 ppm TBT showed
      lower activity and higher frequency of defecation than did controls. These
      figures represent a high level of anxiety and fear and were significant in male
      mice compared with control mice. The skin eruption score was significantly higher
      in the DS-Nh mice fed TBT than in control mice. In the DS-Nh mice fed TBT,
      acanthosis of epidermis and infiltration of inflammatory cells in the dermis were
      more severe than those in controls. CONCLUSION: TBT diet induced alterations in
      emotional behavior in C57BL/6 mice, and also induced early onset and
      deterioration of AD-like lesions in DS-Nh mice.

PMID- 17544635
TI  - Community validation of the U.K. diagnostic criteria for atopic dermatitis in
      Japanese elementary schoolchildren.
AB  - BACKGROUND: A simple list of diagnostic criteria for atopic dermatitis for use in
      epidemiological studies was developed by a U.K. working party. This list served
      well for both hospital patients with skin diseases and in general population
      within the U.K. OBJECTIVES: To validate the U.K. diagnostic criteria in Japanese
      elementary schoolchildren, we collected the questionnaires on regular health
      checkups, which had been completed by parents of schoolchildren in 2001/2002 and
      2004/2005. METHODS: Elementary schoolchildren were examined by dermatologists in
      eight areas (16,152 children) in 2001/2002 and in three areas (3849 children) in
      2004/2005. The questionnaire was distributed to the parents 2 weeks before the
      skin examination, completed by the parents and collected after the survey.
      RESULTS: In 2002/2002 comparing the U.K. diagnostic criteria with the findings on
      clinical examination used as the reference standard, the U.K. criteria (1-year
      prevalence measure) showed a sensitivity of 71.8%, specificity of 89.3% and
      positive predictive value of 44.7%. In 2004/2005 we confirmed that the U.K.
      criteria for a point prevalence measure showed a higher positive predictive value
      (59.9%) compared with that for 1-year prevalence measure (49.3%). CONCLUSION: Now
      that we know the sensitivity and specificity of the U.K. criteria in the
      population examined in this study, we will be able in the near future to estimate
      the prevalence of atopic dermatitis in a similar population with reverse
      operation by questionnaires alone using these criteria without examination by
      dermatologists. Therefore, the validation study of U.K. criteria could be useful
      for future epidemiologic surveys.

PMID- 17544636
TI  - The cost of borderline personality disorder: societal cost of illness in BPD
      patients.
AB  - BACKGROUND: Borderline personality disorder (BPD) is a highly prevalent, chronic
      condition. Because of its very problematic nature BPD is expected to be
      associated with substantial societal costs, although this has never been
      comprehensively assessed. OBJECTIVE: Estimate the societal cost of BPD in the
      Netherlands. STUDY DESIGN: We used a prevalence-based bottom-up approach with a
      sample of 88 BPD patients who enrolled in a multicenter clinical trial comparing
      two kinds of outpatient psychotherapy. Costs were assessed by means of a
      structured interview, covering all healthcare costs, medication, informal care,
      productivity losses, and out-of-pocket expenses. Only BPD-related costs were
      included. All costs were expressed in Euros for the year 2000. A bootstrap
      procedure was performed to determine statistical uncertainty. PATIENTS: All
      patients had been diagnosed with BPD using DSM-IV criteria. Mean age was 30.5
      years and 92% was female. RESULTS: Based on a prevalence of 1.1% and an adult
      population of 11,990,942, we derived that there were 131,900 BPD patients in the
      Netherlands. Total bootstrapped yearly cost of illness was 2,222,763,789 euros
      (1,372,412,403-3,260,248,300 euros), only 22% was healthcare-related. Costs per
      patient were 16,852 euros. CONCLUSIONS: Although healthcare costs of non
      institutionalized Borderline patients might not be disproportionate, total
      societal costs are substantial.

PMID- 17544637
TI  - A perspective on bioconjugated nanoparticles and quantum dots.
AB  - Bioconjugated nanoparticles and quantum dots are among the most exciting
      nanomaterials with promising application potentials in nanomedicine field. These
      applications include biosensing, bioimaging, bioassay, targeted drug delivery and
      new therapeutic agents or method development. Although most of these applications
      are based on the optical properties of nanoparticle materials such as surface
      plasmon resonance, surface enhanced Raman scattering and strong
      photoluminescence, other aspects of nanoparticles such as the catalytic effect
      and amplification effect associated with the nanoscale dimension have also been
      explored. This review presents a narrative summary on the use of bioconjugated
      nanoparticles and quantum dots for biological applications, along with a
      discussion on some critical challenges existing in the field and possible
      solutions that have been or are being developed to overcome these challenges.

PMID- 17544638
TI  - Hydrolysis kinetics in anaerobic degradation of particulate organic material: an
      overview.
AB  - The applicability of different kinetics to the hydrolysis of particulate organic
      material in anaerobic digestion is discussed. Hydrolysis has traditionally been
      modelled according to the first-order kinetics. For complex substrate, the first
      order kinetics should be modified in order to take into account hardly degradable
      material. It has been shown that models in which hydrolysis is coupled to the
      growth of hydrolytic bacteria work well at high or at fluctuant organic loading.
      In particular, the surface-related two-phase and the Contois models showed good
      fits to experimental data from a wide range of organic waste. Both models tend to
      the first-order kinetics at a high biomass-to-waste ratio and, for this reason,
      they can be considered as more general models. Examples on different inhibition
      processes that might affect the degradation of solid waste are reported.
      Acetogenesis or methanogenesis might be the rate-limiting stages in complex
      waste. In such cases, stimulation of hydrolysis (mechanically, chemically or
      biologically) may lead to a further inhibition of these stages, which ultimately
      affects hydrolysis as well. Since the hydrolysis process is characterized by
      surface and transport phenomena, new developments in spatially distributed models
      are considered fundamental to provide new insights in this complex process.

PMID- 17544639
TI  - Leaching of mercury-containing cement monoliths aged for one year.
AB  - A directive from the Swedish Government states that waste containing more than 1%
      of mercury shall be permanently deposited. The stabilization of mercury by
      conversion to a sparingly soluble compound like the sulphide is crucial to ensure
      long-term immobilization in a permanent storage. Immobilization by the
      solidification/stabilization (S/S) method and possible formation of HgS from
      mercury oxide or elemental mercury by reaction with a sulphur source (S or FeS)
      is investigated by a modified version of the NEN 7345 Dutch tank-leaching test.
      The diffusion of mercury during 11 months from 1-year-old mercury containing
      monoliths of Portland and slag cement is demonstrated. In a geologic repository
      under conditions representative of deep granitic bedrock (bicarbonate buffered to
      pH 8.6), a favourable monolith combination is slag cement with addition of the
      iron sulphide troilite. The apparent diffusion coefficient of mercury is
      estimated.

PMID- 17544640
TI  - Compost impacts on dissolved organic carbon and available nitrogen and phosphorus
      in turfgrass soil.
AB  - Compost application to turfgrass soils may increase dissolved organic C (DOC)
      levels which affects nutrient dynamics in soil. The objectives of this study were
      to investigate the influence of compost source and application rate on soil
      organic C (SOC), DOC, NO(3), and available P during 29 months after a one-time
      application to St. Augustinegrass [Stenotaphrum secundatum (Walt.) Kuntze] turf.
      Compost sources had variable composition, yet resulted in few differences in SOC,
      DOC, and NO(3) after applied to soil. Available NO(3) rapidly decreased after
      compost application and was unaffected by compost source and application rate.
      Available P increased after compost application and exhibited cyclical seasonal
      patterns related to DOC. Compost application decreased soil pH relative to
      unamended soil, but pH increased during the course of the study due to irrigation
      with sodic water. Increasing the compost application rate increased SOC by 3
      months, and levels remained fairly stable to 29 months. In contrast, DOC
      continued to increase from 3 to 29 months after application, suggesting that
      compost mineralization and growth of St. Augustinegrass contributed to seasonal
      dynamics. Dissolved organic C was 75%, 78%, and 101% greater 29 months after
      application of 0, 80, and 160 Mg compostha(-1), respectively, than before
      application. Impacts of composts on soil properties indicated that most
      significant effects occurred within a few months of application. Seasonal
      variability of SOC, DOC, and available P was likely related to St. Augustinegrass
      growth stages as well as precipitation, as declines occurred after precipitation
      events.

PMID- 17544642
TI  - Neuropsychology for the primary care physician.

PMID- 17544643
TI  - Clinical neuropsychology: a brief history.

PMID- 17544644
TI  - Differential diagnosis of Alzheimer's dementia and vascular dementia.

PMID- 17544645
TI  - The neuropsychology of Parkinson's disease.

PMID- 17544646
TI  - The neuropsychology of migraine.
AB  - Migraine is a common and recurrent headache disorder that may present with a
      variety of neurologic and non-neurologic manifestations. It has been classified
      into migraine with aura and migraine without aura. Research has shown that
      migraine affects verbal, visuo-spatial memory, and selective attention tasks.
      Cognitive impairments observed in migraineurs have been found to occur during a
      migraine attack, after the attack, and even when the individual does not exhibit
      any residual effects of the attack. Individuals with migraine are at a greater
      risk of developing anxiety and depression. Migraine disability is most commonly
      assessed using the Migraine Disability Assessment Scale (MIDAS), a simple five
      item scale that assesses the individual's level of performance and areas of
      impairment. This review assesses the neuropsychological aspects of the complex
      malady that is migraine.

PMID- 17544647
TI  - Neuropsychological evaluation of the child with epilepsy.

PMID- 17544648
TI  - The role of psychology in the ENH-Bariatric Services Program.

PMID- 17544649
TI  - The neuropsychology of multiple sclerosis.

PMID- 17544650
TI  - The neuropsychology of antisocial personality disorder.
AB  - Antisocial Personality Disorder (APD) is a psychological disorder most commonly
      associated with the legal and criminal justice systems, as many persons arrested
      for the commission of illegal acts meet the diagnostic criteria for this
      disorder, such as deception, manipulation, disregard for the rights of others,
      and a lack of remorse for their behavior. Most researchers agree that this
      disorder stems from brain abnormalities, including the theories of frontal lobe
      dysfunction and differences in the autonomic nervous systems in individuals
      diagnosed with APD. The Integrated Emotional Systems (IES) model, a third model
      of APD, is itself not a brain abnormality, but provides an understanding of
      antisocial characteristics based on dysfunctions in select parts of the brain.
      Based on research using neuropsychological assessments and other techniques,
      several cognitive characteristics appear to exist among these individuals.
      Examples include cognitive inflexibility, attention deficits, and inappropriate
      processing of contextual cues in the environment, sometimes leading to poor
      behavioral choices. Further research is needed to help identify the cause of this
      disorder so that the most appropriate treatments can be made available to these
      individuals.

PMID- 17544651
TI  - The role of pediatric neuropsychological assessment in primary care practice.

PMID- 17544652
TI  - Clinical response by palpation during primary systemic therapy with four dose
      dense cycles doxorubicin and docetaxel in patients with operable breast cancer:
      further results from a randomised controlled trial.
AB  - Primary systemic therapy (PST) allows the observation of tumour response under
      treatment, but little is known regarding the typical course of clinical response
      during such therapy. The aim of this study is to support decision making in case
      of insufficient clinical response. Tumour response was assessed by palpation at
      different times in 436 patients with operable breast cancer from the dose-dense
      biweekly therapy arm of the GEPARDUO phase III trial. The predictive value of
      clinical response for pathologic complete response (pCR), prognostic models to
      assess the prognosis and individual courses of clinical response were
      investigated. Sensitivity and positive predictive value were low, but
      comparatively highest after the 3rd cycle. The predictive value of clinical
      response by palpation for pCR was subsequently limited. The majority of patients
      (68.1%) experienced a consistent decrease in tumour size during PST. The results
      indicate that decisions about further treatment should take place at the earliest
      after the 3rd cycle or 6 weeks of dose-dense PST.

PMID- 17544653
TI  - The Nottingham Prognostic Index - from relative to absolute risk prediction.

PMID- 17544654
TI  - Liver resection for colorectal liver metastasis.
AB  - At some point in the natural course of colorectal cancer up to 50% of patients
      will develop metastasis to the liver. Historically only 20% of these patients
      would have to be deemed resectable, with an intent to cure, at the time of
      presentation. But with recent improvements in cross-sectional imaging,
      chemotherapeutic agents and advances in the techniques of surgical resection the
      emphasis of resection has now changed to 'who is not resectable' as opposed to
      'who is resectable'. There are few contraindications to liver resection on the
      proviso that the patient is fit enough. As a result of this paradigm shift, 5
      year survival rates are approaching 60%. Historically liver resection was
      perceived as a formidable operation but now liver resection for CRLM is safe and
      specialist centres are reporting mortality rates of less than 1%. This review
      briefly covers the standard techniques currently employed and some of the recent
      innovations being developed to improve resectability.

PMID- 17544656
TI  - How much of a difference does it take to make a difference.

PMID- 17544657
TI  - IVF and HPV.

PMID- 17544659
TI  - Statistical power to detect differences.

PMID- 17544661
TI  - Matched designs--intuitively attractive, but the analysis can be problematic.

PMID- 17544663
TI  - Units of measurements are critical in research and patient care.

PMID- 17544665
TI  - Ethics Committee response.

PMID- 17544667
TI  - Synthesis and biological evaluation of 9-deazaguanine derivatives connected by a
      linker to difluoromethylene phosphonic acid as multi-substrate analogue
      inhibitors of PNP.
AB  - 9-(5',5'-difluoro-5'-phosphonopentyl)-9-deazaguanine (DFPP-DG) was designed as a
      multi-substrate analogue inhibitor against purine nucleoside phosphorylase (PNP)
      on the basis of X-ray crystallographic data obtained for a binary complex of 9
      (5',5'-difluoro-5'-phosphonopentyl)guanine (DFPP-G) with calf spleen PNP. DFPP-DG
      and its analogous compounds were adjusted by length of the linker achieved by the
      Sonogashira-coupling reaction between a 9-deaza-9-iodoguanine derivative and
      omega-alkynyldifluoromethylene phosphonates as a key reaction. DFPP-DG is a very
      potent PNP inhibitor with apparent inhibition constants (in the presence of 1 mM
      phosphate) of 4.4 and 8.1 nM versus calf spleen and human erythrocyte PNPs,
      respectively. One of its analogues, homo-DFPP-DG, with longer chain linking
      phosphonate and 9-deazaguanine is even more potent versus human enzyme, with an
      apparent inhibition constant of 5.3 nM (in the presence of 1mM phosphate).

PMID- 17544668
TI  - Synthesis, SAR, and X-ray structure of novel potent DPPIV inhibitors: oxadiazolyl
      ketones.
AB  - Synthesis of a novel series of DPPIV inhibitors with 1,2,4- and 1,3,4-oxadiazolyl
      ketone derivatives and its structure-activity relationships are discussed.
      Compound 18h showed good inhibitory activity against DPPIV and favorable
      pharmacokinetic properties. In vivo pharmacodynamic efficacy and co-crystal
      structure of compound 18h with DPPIV is also described.

PMID- 17544669
TI  - Ferulic acid and benzothiazole dimer derivatives with high binding affinity to
      beta-amyloid fibrils.
AB  - New ferulic acid and benzothiazole dimer derivatives were synthesized and
      evaluated by in vitro competition assay using [(125)I]TZDM for their specific
      binding affinities to Abeta fibrils. In particular, 4a showed the most excellent
      binding affinity (K(i)=0.53 nM), compared to PIB (K(i)=0.77 nM), for
      benzothiazole binding sites of Abeta(1-42) fibrils. This result suggests a
      possibility of a potential AD diagnostic probe for detection of Abeta fibrils.

PMID- 17544670
TI  - Prescribing extended adjuvant letrozole.
AB  - The efficacy of 5 years of adjuvant tamoxifen in preventing disease recurrence in
      patients with breast cancer has been well established. Once patients have
      completed tamoxifen therapy, however, recurrence risk remains but treatment
      options are limited. Aromatase inhibitors such as letrozole are emerging as
      potential alternatives to tamoxifen therapy and as an option after tamoxifen. The
      pioneering MA-17 trial was designed to evaluate the efficacy and safety of
      letrozole in the extended adjuvant setting in postmenopausal women who remained
      disease-free after about 5 years of tamoxifen. The trial was unblinded at first
      interim analysis after letrozole proved more effective than placebo in improving
      disease-free survival. As such, the optimal duration of extended adjuvant
      letrozole was left in question. However, recent results from cohort analysis in
      MA-17 have shown an ongoing and increasing benefit of letrozole for up to 4 years
      after tamoxifen, suggesting that longer periods of extended adjuvant letrozole
      are safe and clinically beneficial.

PMID- 17544671
TI  - Synthesis and evaluation of human T cell stimulating activity of an alpha
      sulfatide analogue.
AB  - A concise synthesis of alpha-sulfatide 1, an analogue of natural glycolipid
      antigens with potential anti-tumor activity, was performed. Two different
      approaches to the alpha-glycosidic bond were explored, resulting in a high yield
      and excellent stereoselectivity. Compound 1 combines the structural features of
      sulfated beta-GalCer (sulfatide) and alpha-GalCer, which activate specific T
      cells. alpha-Sulfatide 1 was stimulatory for CD1d-restricted semi-invariant
      Natural Killer T (iNKT) cell clones, although less potent than alpha-GalCer,
      while it was not recognized by CD1a-restricted sulfatide-specific T cells.

PMID- 17544672
TI  - Bicyclo[2.2.2]octyl esters of dialkylamino acids as antiprotozoals.
AB  - A couple of bicyclo[2.2.2]octyl esters of 2-dialkylaminoacetic acids were
      prepared. Their antiplasmodial and antitrypanosomal activities against
      Trypanosoma brucei rhodesiense (STIB 900) and the K(1) strain of Plasmodium
      falciparum (resistant to chloroquine and pyrimethamine) were determined using
      microplate assays. Structure-activity relationships were discussed. The
      antiprotozoal activities were remarkably increased by insertion of a second basic
      centre. The selectivity indices of the most active compounds are superior in the
      bicyclo-octane series.

PMID- 17544673
TI  - Design, synthesis, and anticonvulsant activity of some sulfamides.
AB  - As part of our search for potential anticonvulsant agents, a set of compounds
      were designed, synthesized, and evaluated against MES and PTZ tests. Bioisosteric
      functional group information was used to design a new functionality, sulfamides,
      that complies with the requirements of the pharmacophore previously defined. Some
      of the molecules showed a promising anticonvulsant profile as selective anti-MES
      drugs, being active at low concentrations (30mg/kg). The biological data were
      confirmed in Phase II of the Anticonvulsant Drug Development Program of the
      National Institute of Health.

PMID- 17544674
TI  - IL-10 and IL-6 gene polymorphisms as potential host susceptibility factors in
      Brucellosis.
AB  - Several genes encoding for different cytokines may play crucial roles in host
      susceptibility to Brucellosis, since the cytokine production capacity varies
      among individuals and depends on the cytokine gene polymorphism. The association
      of the cytokine gene polymorphisms with the development of Brucellosis was
      investigated in this study. DNA samples were obtained from a Turkish population
      of 40 patients with Brucellosis, and 50 healthy control subjects. All genotyping
      (IL-6, IL10, IFN-gamma, TGF-beta and TNF-alpha) experiments were performed using
      sequence-specific primers PCR (PCR-SSP). When compared to the healthy controls,
      the frequencies of high/intermediate producing genotypes of IL-10 and high
      producing genotype of IL-6 were significantly more common in the patient group.
      These results suggest that IL-10 and IL-6 gene polymorphisms may affect
      susceptibility to Brucellosis and increase risk of developing the disease. In
      order to confirm the biological significance of our results, further studies
      should be performed in larger population groups.

PMID- 17544676
TI  - Philosophy and theory of holism.
AB  - Holistic nurses believe that the human being, composed of a mind, body and soul
      integrated into an inseparable whole that is greater than the sum of the parts,
      is in constant interaction with the universe and all that it contains. Health and
      well-being depend on attaining harmony in these relationships. Healing is the
      journey toward holism. Using presence, intent, unconditional acceptance, love,
      and compassion, holistic nurses can facilitate growth and healing and help their
      clients to find meaning in their life experiences, life purpose, and reason for
      being.

PMID- 17544677
TI  - Holistic nursing as a specialty: holistic nursing - scope and standards of
      practice.
AB  - This article describes the Holistic Nursing: Scope and Standards of Practice. It
      defines holistic nursing, its five core values, and its practice standards. These
      include holistic philosophy, theory, and ethics; holistic caring process;
      holistic communication, therapeutic environment, and cultural diversity; holistic
      education and research; and holistic nurse self-care. Educational preparation for
      holistic nursing and settings in which holistic nurses practice are also
      explored.

PMID- 17544678
TI  - Legal parameters of alternative-complementary modalities in nursing practice.
AB  - Complementary and alternative healing modalities are increasing in popularity.
      Partially in response to client demand and partially because of a strong history
      in providing care encompassing the whole person, nurses have responded by
      incorporating selected alternative therapies within select professional services.
      There are questions, however, as to whether some or all of these modalities are
      within the boundaries of nursing practice. Because most professional practice
      acts are vague in relation to specific therapies, a model for legal analysis is
      presented.

PMID- 17544679
TI  - Holistic assessment and care: presence in the process.
AB  - Holistic assessment and care are inseparable from the nursing process. Holistic
      nursing practice informed by a philosophy of holism balancing art and science
      recognizes the interconnectedness of body, mind, and spirit. Holistic practice
      draws on knowledge, theories, expertise, intuition, and creativity. The purpose
      of this article is to place nursing in the context of holistic practice; to
      explicate the role of presence as an essential condition for holistic care; and
      to provide an example of the holistic caring process that incorporates theory,
      presence, and practice documented in the standard formats. A holistic approach to
      nursing integrates process and presence in the provision of care. Process alone
      is empty without presence. Presence alone is insufficient without the process.

PMID- 17544680
TI  - Promoting behavior change: making healthy choices in wellness and healing choices
      in illness - use of self-determination theory in nursing practice.
AB  - This article explores more efficacious strategies for holistic nurses to promote
      healthy behavior choices in their clients. It presents an overview of self
      determination theory (SDT) and describes research evidence that supports the
      application of SDT to promoting healthy behavior change in clients. When nurses
      act in ways that support clients' innate needs for autonomy, competence, and
      relatedness, clients may be more successful at internalizing self-regulation and
      more inclined to adopt and maintain lifelong behavioral changes. Some examples of
      nursing interventions to motivate behavior change are outlined in this article.

PMID- 17544681
TI  - Energy-based modalities.
AB  - Research on touch therapies is still in the early stages of development. Studies
      of Therapeutic Touch, Healing Touch, and Reiki are quite promising; however, at
      this point, they can only suggest that these healing modalities have efficacy in
      reducing anxiety; improving muscle relaxation; aiding in stress reduction,
      relaxation, and sense of well-being; promoting wound healing; and reducing pain.
      The multidimensional aspects of healing inherent in patient care continue to be
      expanded and facilitated by our understanding and application of energy
      therapies.

PMID- 17544682
TI  - Imagery in the clinical setting: a tool for healing.
AB  - This article addresses the why and how of imagery and its relation with holistic
      theories. The description of clinical applications, program development, and
      research demonstrates successful interventions in virtually every area of
      nursing. Case examples show the profound healing that is experienced by the
      patient and the nurse simultaneously through this work. Imagery is harmless, is
      time- and cost-effective, and creates a healing partnership between the nurse and
      patient.

PMID- 17544683
TI  - Meeting clients' spiritual needs.
AB  - True holistic care requires attention to spiritual as well as physical needs, but
      many health care providers do not feel comfortable discussing spiritual matters
      with clients. Although recognized by national nursing groups as a standard of
      care, nurses are not well prepared or rewarded for spiritual care efforts. There
      are several spiritual assessment tools available and many suggestions for
      interventions, but little research-based evidence on the effectiveness of
      spiritual care assessments or interventions. Nurses are well positioned by their
      continued intimate contact with clients and the importance of caring to nursing
      to lead the health care profession in developing spiritual care theory and
      practices.

PMID- 17544684
TI  - Creating a holistic environment for practicing nurses.
AB  - Until nurse administrators and nurse educators focus on improving the nursing
      practice environments in which we lead and teach others, it is likely to be
      extremely difficult for nurses to succeed in providing holistic care to clients.
      To promote a holistic practice environment for nurses, we need to find creative
      ways to apply newer leadership theories in practice and education. A heightened
      self-awareness of our own emotions and how we influence others can promote more
      positive relationships, and thus a more nurturing practice environment, for
      nurses of all ages, cultures, and levels of experience.

PMID- 17544685
TI  - Teaching holistic nursing: the legacy of Nightingale.
AB  - This article emphasizes the importance of holistic concepts in nursing and
      curriculum development. Grounded in the work of Florence Nightingale, nursing
      education prepares practitioners to meet the holistic needs of clients. The basic
      tenets offered by the American Holistic Certification Corporation and the
      American Holistic Nurses' Association are used to describe essential content in a
      nursing program emphasizing holism. Strategies for introducing holistic nursing
      into curriculum and overcoming barriers to including holistic nursing in nursing
      education are discussed. Examples are provided through the experiences of two
      schools of nursing that successfully incorporated holistic nursing concepts.

PMID- 17544686
TI  - Research paradigms and methods for investigating holistic nursing concerns.
AB  - Holistic nursing is a discipline focused on healing the whole person and
      dedicated to understanding and supporting the premise of holistic health of the
      patient and promoting healing in practitioners, patients, families, social
      groups, and communities. An explication of knowledge related to caring and
      healing in the human health experience and in holistic nursing is informed by the
      individual nurse's paradigmatic stance. Holistic nursing research is complex and
      focuses on healing, particularly healing of self, others, systems, and
      communities at large. This article discusses the competing paradigmatic
      perspectives, theoretic perspectives supporting holistic research, fundamental
      patterns of knowing and knowledge generation, a framework for holistic research,
      and the challenges of conducting holistic research. Recommendations for future
      research agenda are presented.

PMID- 17544689
TI  - Anesthesia, antisepsis, microscope: the confluence of neurotology.
AB  - Neurotology and skull base surgery slowly emerged out of a confluence of
      interrelated disciplines and technologies over the past century to become the
      field that we know today. Its formation required the marriage of neurosurgery and
      otology, the introduction of the operating microscope, and advances in surgical
      technique, anesthesia, and radiology. Along the way, the field also began
      involving specialists within ophthalmology and craniofacial and plastic and
      reconstructive surgery. Lastly, and perhaps most importantly, the formation of
      neurotology and skull base surgery required pioneering surgeons who were willing
      to push the boundaries of their training, sometimes under the ridicule or scorn
      of the medical establishment. This historical overview focuses upon the origins
      of the specialty, from the birth of otology and neurosurgery up through the last
      quarter century.

PMID- 17544687
TI  - Novel toxicity of the unedited GluR2 AMPA receptor subunit dependent on surface
      trafficking and increased Ca2+-permeability.
AB  - RNA editing modifies the GluR2 AMPA receptor subunit pore loop at the Q/R site
      and limits receptor Ca(2+) permeability. Editing failure is implicated in
      neurodegenerative diseases, including amyotrophic lateral sclerosis. We show that
      channels with unedited GluR2 are highly toxic in cultured hippocampal neurons.
      Toxicity exceeds that of other Ca(2+)-permeable AMPA receptor types and is
      influenced by agonist binding site mutations, ability to desensitize, and
      extracellular Ca(2+) levels. Significantly, toxicity also depends on GluR2's
      constitutive surface trafficking, a function dependent on GluR2 C-terminal domain
      interaction with NSF, a specialized chaperone. We have exploited the interaction
      between unedited GluR2 and NSF to reduce GluR2 surface levels. We show that a
      peptide that blocks the GluR2-NSF interaction reduces unedited GluR2 toxicity by
      reducing receptor surface expression. Peptide block of trafficking provides a
      model for design of drugs to reduce unedited GluR2 excitotoxicity in
      neurodegenerative diseases that result from editing failure.

PMID- 17544690
TI  - Advances in skull base imaging.
AB  - Despite being introduced in the 1970s and 1980s, CT and MRI continue to be the
      primary imaging modalities for the temporal bone and skull base. Although the
      general concepts and physics remain the same, the images obtained currently are
      far superior. Augmenting these traditional modalities are nuclear medicine
      imaging techniques, functional imaging, and the fusion of different techniques.
      Advances in these areas are expanding our options and illuminating pathology in
      unique ways. As basic physiologic processes are better understood, new
      opportunities for novel imaging techniques should arise.

PMID- 17544691
TI  - Intracranial pressure concerns in lateral skull base surgery.
AB  - This article serves as a concise review of cerebrospinal fluid metabolism and
      intracranial pressure regulation for otolaryngologists and lateral skull base
      surgeons. It examines the methodologies for maintaining cerebrospinal fluid
      homeostasis by preventing and treating acute elevations of intracranial pressure
      encountered during lateral skull base surgery.

PMID- 17544692
TI  - Evaluation and management of endolymphatic sac and duct tumors.
AB  - The endolymphatic sac tumor is a slow-growing, locally aggressive neoplasm that
      originates from the epithelium of the endolymphatic sac and duct. Disease
      progression can lead to profound sensorineural hearing loss, posterior fossa
      invasion, brainstem compression, drop metastasis, and eventual death. Early
      diagnosis and surgical attention are the primary objectives in the management of
      patients who have endolymphatic sac tumor. This article describes the latest
      rationale and techniques for hearing preservation surgery and a review of the
      latest developments surrounding this disease entity.

PMID- 17544693
TI  - Lesions of the petrous apex: diagnosis and management.
AB  - Management of petrous apex pathology poses a unique challenge even to the most
      seasoned skull base surgeons. The central location in the skull base with
      adjacent critical neurovascular structures makes access to this region more than
      a trivial matter. Significant advances in diagnostic imaging have greatly
      facilitated the diagnosis of petrous apex lesions. The introduction of modern
      skull base surgery techniques also has provided skull base surgeons with numerous
      avenues to the petrous apex while significantly decreasing morbidity. The latest
      diagnostic and management strategies are discussed and an update of some of the
      more common pathologic entities is provided.

PMID- 17544694
TI  - Guiding patients through the choices for treating vestibular schwannomas:
      balancing options and ensuring informed consent.
AB  - Counseling patients who are diagnosed with vestibular schwannomas, formerly known
      as acoustic neuromas, can be challenging. The health care provider has the
      responsibility to explain, in understandable language, to the patient or legal
      representative the proposed treatment options, risks and complications associated
      with each form of treatment, and alternatives to treatment, including no therapy.
      Patients should be encouraged to gather information before making a treatment
      decision. For the physicians managing these patients, information should be
      delivered in a balanced way to ensure patient understanding of their options
      leading to adequate informed consent.

PMID- 17544695
TI  - LINAC radiosurgery and radiotherapy treatment of acoustic neuromas.
AB  - This article provides an introduction to radiation therapy as it applies to
      intracranial tumors. It also provides a review of the natural growth progression
      of acoustic neuromas and accuracy of tumor size determination. Literature on the
      use of linear accelerator stereotactic radiosurgery and fractionated radiotherapy
      in acoustic neuroma management is reviewed and summarized. Specifically, the
      rates of reported tumor control, hearing preservation, facial and trigeminal
      nerve complications, and hydrocephalus are analyzed. Although the complication
      rates associated with linear accelerator therapy are relatively low, hearing
      preservation is poor and acoustic neuroma control is variable.

PMID- 17544696
TI  - Stereotactic radiation techniques in the treatment of acoustic schwannomas.
AB  - Medical decision-making is based on benefit-to-cost analysis. Optimally,
      treatment obtains a high degree of benefit while minimizing the physical, social,
      and financial costs. The goals of the treatment of acoustic schwannomas are
      prohibiting tumor growth and alleviation of symptoms caused by damage to local
      structures. These symptoms-tinnitus, ataxia, and hearing loss--secondary to
      eighth nerve dysfunction, as well as symptoms arising from damage to adjacent
      structures such as the facial nerve, trigeminal nerve, or pons, can be caused by
      tumor growth or treatment. Determination of optimal therapy must also take into
      account an understanding of the natural history of the disease, because acoustic
      schwannomas are slow-growing benign tumors that when left untreated, usually
      enlarge over time and cause problems.

PMID- 17544697
TI  - Surgical approaches and complications in the removal of vestibular schwannomas.
AB  - Vestibular schwannomas are benign tumors that usually originate from the balance
      portion of cranial nerve VIII. The treatment options currently available for
      vestibular schwannomas include observation with serial imaging, stereotactic
      radiation, and microsurgical removal. Although the ultimate goal in treatment of
      vestibular schwannomas is preservation of life, the best option for each patient
      depends on symptoms, tumor size, tumor location, and the patient's general health
      and age. Surgical exposure of the cerebellopontine angle for removal of
      vestibular schwannomas can be performed safely via a translabyrinthine,
      retrosigmoid, and middle fossa approach. Each approach has its advantages and
      disadvantages. The goal of surgery is complete eradication of tumor with
      preservation of hearing and facial nerve function when possible.

PMID- 17544698
TI  - Image-guided technique in neurotology.
AB  - To date, clinical application of image-guided surgery (IGS) to
      otology/neurotology has been limited, but a large potential market and numerous
      applications support use. Such applications include control of surgical
      instruments (eg, turning off a drill when close to an anatomic boundary), robotic
      surgery (eg, robotic mastoidectomy), and minimally invasive surgery (eg,
      percutaneous cochlear implantation).

PMID- 17544699
TI  - Neurotologic surgery for glomus tumors.
AB  - This article reviews the important aspects of glomus tumor management. The
      biology and histology of these tumors are unique and have an impact on treatment
      strategies. Nonsurgical options, such as radiation therapy, are discussed.
      Surgical resection can be performed safely only after appropriate diagnostic
      testing is completed. Imaging and other diagnostic testing are explored. The
      various resection and reconstructive strategies are discussed.

PMID- 17544700
TI  - Management of complications in neurotology.
AB  - Neurotologic and skull base surgery involves working around important
      neurovascular and neurotologic structures and can incur unwarranted
      complications. Knowledge of surgical anatomy, good preoperative planning,
      intraoperative monitoring, and excellent microsurgical technique contribute to
      minimizing and avoiding complications. In the event of a complication, however,
      the neurotologic surgeon should be prepared to manage it. In this article, the
      authors focus on the management of complications encountered in neurotologic
      skull base surgery, including hemorrhage, stroke, cerebrospinal fluid leak,
      extraocular motility deficits, facial paralysis, hearing loss, dizziness, lower
      cranial nerve palsies, and postoperative headache.

PMID- 17544701
TI  - Ototoxicity of ototopical drops--an update.
AB  - Various topical preparations are widely used for treating external otitis, acute
      otitis media with perforation, post-tympanostomy tube otorrhea, and chronic
      suppurative otitis media. Solutions and suspensions that enter the middle ear
      through a perforated tympanic membrane can reach the inner ear by crossing
      through the round window membrane. The safety of various components of otic
      solutions used in this way, particularly aminoglycosides, corticosteroids,
      solvents, and preservatives, has been questioned in light of their ototoxic
      potential. The authors' objective is to review the literature discussing the
      safety of commonly used classes of otic preparations in settings in which the
      constituents can access the middle and inner ear in high concentrations and
      discuss their clinical experience with ototoxicity and experience with medical
      legal issues.

PMID- 17544702
TI  - Surface EMG analysis on normal subjects based on isometric voluntary contraction.
AB  - The objective of this study was to compute reference SEMG values for normal
      subjects of 13 parameters extracted in the time, frequency and bispectrum domain,
      from the Biceps Brachii (BB) muscle generated under isometric voluntary
      contraction (IVC). SEMG signals were recorded from 94 subjects for 5s at 10, 30,
      50, 70 and 100% of maximum voluntary contraction (MVC). The Wilcoxon signed rank
      test was applied to detect significant differences or not at p<0.05 between force
      levels for each of the 13 parameters. The main findings of this study can be
      summarized as follows: (i) The time domain parameters turns per second and number
      of zero crossings per second increase significantly with force level. (ii) The
      power spectrum median frequency parameter decreases significantly with force
      level, whereas maximum power and total power increase significantly with force
      level. (iii) The bispectrum parameter, maximum amplitude, increases significantly
      with force level with the exception the transition from 30% to 50% MVC. Although,
      the tests for Gaussianity and linearity show no significant difference with force
      level, the SEMG signal exhibits a more Gaussian distribution with increase of
      force up to 70% MVC. The SEMG linearity test, which is a measure of how constant
      the bicoherence index is in the bi-frequency domain, shows that the signal's
      bicoherence index is less constant (hence, the signal is less linear) at 70% of
      MVC compared to 10, 30, 50 and 100% MVC. (iv) The time domain parameters have
      good correlation between them as well as, between each one of them and maximum
      and total power. The median frequency has a good (negative) correlation with the
      bispectrum peak amplitude. (v) No significant differences exist between values
      based on gender or age. The findings of this study can further be used for the
      assessment of subjects suffering with neuromuscular disorders, or in the
      rehabilitation laboratory for monitoring the elderly or the disabled, or in the
      occupational medicine laboratory.

PMID- 17544703
TI  - Heart beats brain: The problem of detecting alpha waves by neuronal current
      imaging in joint EEG-MRI experiments.
AB  - It has been suggested recently that the influence of the neuro-magnetic field
      should make electrical brain activity directly detectable by MRI. To test this
      hypothesis, we performed combined EEG-MRI experiments which aim to localize the
      neuronal current sources of alpha waves (8-12 Hz), one of the most prominent EEG
      phenomena in humans. A detailed analysis of cross-spectral coherence between
      simultaneously recorded EEG and MRI time series revealed no sign of alpha waves.
      Instead the EEG-MRI approach was found to be hampered by artefacts due to cardiac
      pulsation, which extend into the frequency band of alpha waves. Separate brain
      displacement mapping experiments confirmed that not only the EEG but also the MRI
      signal is confounded by harmonics of the cardiac frequency even at 10 Hz and
      beyond. This well-known ballistocardiogram artefact cannot be avoided or
      eliminated entirely by available signal processing techniques. Therefore we must
      conclude that current EEG-MRI methodology based on correlation analysis lacks not
      only the sensitivity but also the specificity required for the reliable detection
      of alpha waves.

PMID- 17544704
TI  - A molecular assessment of northeast Pacific Alaria species (Laminariales,
      Phaeophyceae) with reference to the utility of DNA barcoding.
AB  - Despite their relatively complex morphologies, species in the genus Alaria
      Greville are notoriously difficult to identify with certainty. Morphological
      characters, often influenced by environmental factors, make individuals in
      similar habitats artificially appear related. Species identification would,
      therefore, benefit greatly from the application of molecular tools. We applied
      DNA barcoding, using the 5' end of the cytochrome c oxidase I (coxI-5') gene from
      the mitochondrial genome, to define species limits and relationships in northeast
      Pacific populations of Alaria. This emerging technique is being employed to
      catalogue species diversity worldwide, particularly among animals, and it has
      been shown to be sensitive enough to discriminate between closely related
      species. However, the utility of this marker for identifying or categorizing the
      majority of life remains unclear. We compared the resolution obtained with this
      marker to two other molecular systems commonly used in algal research: the
      nuclear internal transcribed spacer (ITS) of the ribosomal cistron, and the
      plastid Rubisco operon spacer (rbcSp). In agreement with previous results, Alaria
      fistulosa Postels & Ruprecht, with its distinct morphological, ecological and
      molecular features, stands apart from the other species in the genus and we
      establish Druehlia gen. nov. to accommodate it. For the remaining isolates,
      distinct mitochondrial haplotypes resolved with the barcode data indicate a
      period of genetic isolation for at least three incipient species in the northeast
      Pacific, whereas unexpected levels and patterns of ITS variation, as well as the
      extreme morphological plasticity found among these isolates, have most probably
      resulted from a recent collapse in species barriers. The cloning of ITS amplicons
      revealed multiple ITS copies in several individuals, further supporting this
      hypothesis.

PMID- 17544705
TI  - Psychiatric events in epilepsy.
AB  - Psychiatric events are thought to be more frequent in people with epileptic
      seizures than in the general population. However, inter-ictal psychiatric events
      attributable to epilepsy remain controversial. The aim of the present study was
      to evaluate the occurrence of psychiatric events in a population of fairly
      unselected patients with epilepsy and in the general population, and the
      correlation between psychiatric complaints and selected demographic and disease
      characteristics. The survey was part of a multicentre prospective cohort study of
      everyday life risks conducted in eight European countries and comparing referral
      children and adults with epilepsy referred to secondary/tertiary centers to age-
      and sex-matched non-epileptic controls. Nine hundred and fifty-one patients with
      epilepsy and 909 controls were studied. Each patient and his/her control received
      a diary to record any accident or illness, with severity, circumstances, causes,
      consequences, and (for the cases) the possible relation to a seizure. The follow
      up period ranged between 1 and 2 years. Fifty-eight psychiatric events occurred
      in 25 patients (2.6%) and 88 in 19 controls (2.1%). Housewives (9.3%) and
      unemployed persons (4.1%) were mostly affected. No correlation was found between
      psychiatric events, demographic and disease characteristics. Our results suggest
      that people with epilepsy if unselected are not at higher risk for psychiatric
      disorders than the general population.

PMID- 17544706
TI  - Decreased relative efficacy of the ketogenic diet for children with surgically
      approachable epilepsy.
AB  - PURPOSE: In children with intractable, surgically approachable epilepsy, the
      ketogenic diet is often perceived as less efficacious than surgery. METHODS: A
      retrospective chart review was performed of 554 children started on the ketogenic
      diet since 1994. Forty-five children were identified as surgical candidates, with
      at least 2 focal routine EEGs, ictal video-EEG, and corresponding focal
      neuroimaging findings, of whom 24 eventually had resective surgery and were
      followed subsequently. A comparison cohort group was also created of 45 children
      matched for age and seizure frequency that received the diet but were not
      surgical candidates (multifocal or generalized seizures). RESULTS: Of the 24
      children who received both dietary and surgical therapies, there was a higher
      likelihood after 6 months of both >90% seizure reduction (71% versus 17%) and
      seizure freedom (63% versus 0%) following surgery, both p < 0.0001. Similarly,
      the 45 cohort children who were not surgical candidates were more likely to be
      seizure-free (29% versus 13%, p = 0.041) and remained on the diet for shorter
      duration (10 months versus 18 months, p = 0.035) compared to the surgical group.
      CONCLUSION: Children with surgically approachable epilepsy do respond to the
      diet, but are more likely to be seizure-free following surgery.

PMID- 17544707
TI  - Coxsackievirus B3 affects endothelial tight junctions: possible relationship to
      ZO-1 and F-actin, as well as p38 MAPK activity.
AB  - Tight junction (TJ) plays a pivotal role in preventing the invasion of pathogens
      from the blood to extracellular environment. However, the mechanisms by which
      Group B coxsackievirus 3 (CVB(3)) can get through TJ from the apical surface
      still remain obscure. In the present study, the human umbilical vein endothelial
      cell (HUVEC) was utilized to investigate the alterations in F-actin and ZO-1
      status, permeability as well as p38 mitogen-activated protein kinase (MAPK)
      activity in response to CVB(3) by means of fluorescence labeling, flow cytometry,
      and macromolecule permeability assay. We found that CVB(3) was able to induce
      reorganization of F-actin and redistribution of ZO-1, increase the level of F
      actin, and elevate the permeability of FITC-albumin. Moreover, CVB(3)-mediated
      the above effects involve in P38 MAPK activation. Our preliminary study indicates
      that CVB(3)-induced alteration in permeability may be attributed to disruption of
      F-actin and ZO-1 organizations and that SB203580, a specific P38 MAPK inhibitor,
      can reverse these effects. The precise mechanisms underlying the CVB(3)-mediated
      effects on HUVECs need to be studied further.

PMID- 17544718
TI  - Chronic oral methylphenidate administration to periadolescent rats yields
      prolonged impairment of memory for objects.
AB  - Methylphenidate (MPD) is widely prescribed for the treatment of attention deficit
      disorders in children and has generally been thought to be free of significant
      side effects when administered at recommended therapeutic doses. However, recent
      behavioral research with laboratory rodents has indicated that, like other
      psychostimulants with which it shares neurotransmitter-modulating properties,
      chronically administered MPD can bring about lasting and potentially detrimental
      alterations in brain function. Some of these may involve changes in the
      neuromodulatory input from noradrenergic and dopaminergic systems that project to
      the prefrontal cortex and hippocampus, regions with significant roles in several
      cognitive functions, including those critical to memory formation. To investigate
      the possibility of cognitive impairment, the effects of a regimen of chronic MPD
      on the performance of an object recognition task known to rely on the integrity
      of systems involved in rodent memory was assessed. The drug, at doses of 2, 3 or
      5mg/kg, was delivered twice daily to periadolescent rats via an oral
      administration technique on either 11 or 21 treatment days. Subsequent to this
      period, the animals were subjected to an object recognition test at 14, 28, and
      42 days after their last MPD treatment. In each of these tests, exploration time
      for two objects, one novel and one previously encountered (3h earlier), was
      assessed. Longer exploration of the novel object was considered evidence of
      retained memory for the familiar object. It was found that rats exposed to 3 or
      5mg/kg (b.i.d.) on 21 occasions exhibited no significant preference for
      exploration of the novel object at any of the three post-treatment intervals.
      This finding was interpreted as evidence of a persisting MPD-induced impairment
      of recognition memory in these animals.

PMID- 17544731
TI  - Different probiotic properties for Lactobacillus fermentum strains isolated from
      swine and poultry.
AB  - Systematic procedures were used to evaluate the probiotic properties of
      Lactobacillus fermentum (L. fermentum) strains isolated from swine and poultry.
      The major properties included their capabilities to adhere to the intestinal
      epithelium of swine and poultry, the inhibition on pathogenic bacteria, and their
      tolerance to the gastric juice and bile salts. Results showed that L. fermentum
      strains from poultry digestive tract showed better adherence to the swine
      intestine and chicken crop epithelial cells as compared to those strains from the
      swine origin. In addition, six strains from poultry and one strain from swine
      showed adhesion specificity to their own intestinal epithelium. Four poultry
      isolates and one swine isolate were able to adhere to the epithelial cells from
      both swine and chicken. For gastric juice and bile tolerance, most of the strains
      isolated from swine or poultry were acid tolerant but less strains were bile
      intolerant. The spent culture supernatant (SCS) of these L. fermentum strains
      showed antagonistic effect against the indicator bacteria, such as Escherichia
      coli, Salmonella spp., Shigella sonnei and some enterotoxigenic Staphylococcus
      aureus. From the above studies, some L. fermentum strains isolated from poultry
      were found to have the probiotic properties required for use in animal feed
      supplement. This study suggested that poultry digestive tract may serve as
      potential source for the isolation of probiotic lactic acid bacteria.

PMID- 17544732
TI  - Selected prebiotics support the growth of probiotic mono-cultures in vitro.
AB  - The aim of the present study was to identify suitable prebiotics for synergistic
      combinations with representative probiotics from the lactobacilli and
      bifidobacterium genera. Eleven different types of commercially available
      carbohydrates and compounds were screened in basal media for their effects on the
      growth of the probiotic cultures Lactobacillus acidophilus LAFTI L10 (L10),
      Bifidobacterium animalis lactis LAFTI B94 (B94) and Lactobacillus casei LAFTI L26
      (L26). Growth of these probiotics was investigated by measuring optical density
      (OD) levels over a period of 48 h. The results of this study showed that all
      three probiotic strains were able to utilize a range of carbohydrates. Maximal
      growth of L10 was observed in basal medium supplemented with soybean
      oligosaccharide (SOS), followed by fructooligosaccharide (FOS) and inulin, while
      maximal growth of B94 was observed in basal medium supplemented with SOS,
      followed by raffinose, FOS, beta-glucan hydrolysate, inulin and Fibregum TAN. L26
      was shown to exhibit maximal growth in basal medium supplemented with FOS
      followed by inulin, SOS, beta-glucan hydrolysate and beta-glucan concentrate. The
      results of this study indicate that several carbohydrates/compounds can enhance
      the growth of these representative probiotic strains in vitro.

PMID- 17544743
TI  - A systematic analysis of T-DNA insertion events in Magnaporthe oryzae.
AB  - We describe here the analysis of random T-DNA insertions that were generated as
      part of a large-scale insertional mutagenesis project for Magnaporthe oryzae.
      Chromosomal regions flanking T-DNA insertions were rescued by inverse PCR,
      sequenced and used to search the M. oryzae genome assembly. Among the 175
      insertions for which at least one flank was rescued, 137 had integrated in single
      copy regions of the genome, 17 were in repeated sequences, one had no match to
      the genome, and the remainder were unassigned due to illegitimate T-DNA
      integration events. These included in order of abundance: head-to-tail tandem
      insertions, right border excision failures, left border excision failures and
      insertion of one T-DNA into another. The left borders of the T-DNA were
      frequently truncated and inserted in sequences with micro-homology to the left
      terminus. By contrast the right borders were less prone to degradation and
      appeared to have been integrated in a homology-independent manner. Gross genome
      rearrangements rarely occurred when the T-DNAs integrated in single-copy regions,
      although most insertions did cause small deletions at the target site.
      Significant insertion bias was detected, with promoters receiving two times more
      T-DNA hits than expected, and open reading frames receiving three times fewer. In
      addition, we found that the distribution of T-DNA inserts among the M. oryzae
      chromosomes was not random. The implications of these findings with regard to
      saturation mutagenesis of the M. oryzae genome are discussed.

PMID- 17544744
TI  - G8's promises to Africa.

PMID- 17544745
TI  - The deteriorating health situation in Iraq.

PMID- 17544746
TI  - Rosiglitazone: seeking a balanced perspective.

PMID- 17544747
TI  - The prosecution of research--experience from Singapore.

PMID- 17544748
TI  - Human papillomavirus vaccines to prevent cervical cancer.

PMID- 17544749
TI  - Absorbable coronary stents.

PMID- 17544750
TI  - Lowering homocysteine for stroke prevention.

PMID- 17544751
TI  - Protecting abused children.

PMID- 17544753
TI  - Uche Amazigo: overcoming onchocerciasis in Africa.

PMID- 17544754
TI  - Mild versus standard in-vitro fertilisation techniques.

PMID- 17544756
TI  - Mild versus standard in-vitro fertilisation techniques.

PMID- 17544757
TI  - Assessing drug-related harm.

PMID- 17544758
TI  - Assessing drug-related harm.

PMID- 17544759
TI  - Influenza vaccination for elderly people and their care workers.

PMID- 17544761
TI  - Female genital mutilation in Egypt.

PMID- 17544762
TI  - Where is the evidence that low birthweight leads to obesity?

PMID- 17544763
TI  - Clinical trials in the developing world.

PMID- 17544764
TI  - Insulin crisis in Iraq.

PMID- 17544765
TI  - Varicella vaccine and fatal outcome in leukaemia.

PMID- 17544766
TI  - Effect of prophylactic human papillomavirus L1 virus-like-particle vaccine on
      risk of cervical intraepithelial neoplasia grade 2, grade 3, and adenocarcinoma
      in situ: a combined analysis of four randomised clinical trials.
AB  - BACKGROUND: Cervical cancer and its obligate precursors, cervical intraepithelial
      neoplasia grades 2 and 3 (CIN2/3), and adenocarcinona in situ (AIS), are caused
      by oncogenic human papillomavirus (HPV). In this combined analysis of four
      clinical trials we assessed the effect of prophylactic HPV vaccination on these
      diseases. METHODS: 20,583 women aged 16-26 years were randomised to receive
      quadrivalent HPV6/11/16/18 vaccine (n=9087), its HPV16 vaccine component
      (n=1204), or placebo (n=10 292). They underwent periodic Papanicolaou testing,
      with colposcopy or biopsy for detected abnormalities. The primary composite
      endpoint was the combined incidence of HPV16/18-related CIN2/3, AIS, or cervical
      cancer. These trials are registered at ClinicalTrials.gov, numbers NCT00365378,
      NCT00365716, NCT00092521, and NCT00092534. FINDINGS: Mean follow-up was 3.0 years
      (SD 0.66) after first dose. In women negative for HPV16 or HPV18 infection during
      the vaccination regimen (n=17 129, per protocol), vaccine efficacy was 99% for
      the primary endpoint (95% CI 93-100), meeting the statistical criterion for
      success. In an intention-to-treat analysis of all randomised women (including
      those who were HPV16/18 naive or HPV16/18-infected at day 1), efficacy was 44%
      (95% CI 31-55); all but one case in vaccine recipients occurred in women infected
      with HPV16 or HPV18 before vaccination. In a second intention-to-treat analysis
      we noted an 18% reduction (95% CI 7-29) in the overall rate of CIN2/3 or AIS due
      to any HPV type. INTERPRETATION: Administration of HPV vaccine to HPV-naive
      women, and women who are already sexually active, could substantially reduce the
      incidence of HPV16/18-related cervical precancers and cervical cancer.

PMID- 17544767
TI  - Temporary scaffolding of coronary arteries with bioabsorbable magnesium stents: a
      prospective, non-randomised multicentre trial.
AB  - BACKGROUND: Coronary stents improve immediate and late results of balloon
      angioplasty by tacking up dissections and preventing wall recoil. These goals are
      achieved within weeks after angioplasty, but with current technology stents
      permanently remain in the artery, with many limitations including the need for
      long-term antiplatelet treatment to avoid thrombosis. We report a prospective
      multicentre clinical trial of coronary implantations of absorbable magnesium
      stents. METHODS: We enrolled 63 patients (44 men; mean age 61.3 [SD 9.5 years])
      in eight centres with single de novo lesions in a native coronary artery in a
      multicentre, non-randomised prospective study. Follow-up included coronary
      angiography and intravascular ultrasound at 4 months and clinical assessment at 6
      months and 12 months. The primary endpoint was cardiac death, non-fatal
      myocardial infarction, or clinically driven target lesion revascularisation at 4
      months FINDINGS: 71 stents, 10-15 mm in length and 3.0-3.5 mm in diameter, were
      successfully implanted after pre-dilatation in 63 patients. Diameter stenosis was
      reduced from 61.5 (SD 13.1%) to 12.6 (5.6%) with an acute gain of 1.41 mm (0.46
      mm) and in-stent late loss of 1.08 mm (0.49 mm). The ischaemia-driven target
      lesion revascularisation rate was 23.8% after 4 months, and the overall target
      lesion revascularisation rate was 45% after 1 year. No myocardial infarction,
      subacute or late thrombosis, or death occurred. Angiography at 4 months showed an
      increased diameter stenosis of 48.4 (17.0%). After serial intravascular
      ultrasound examinations, only small remnants of the original struts were visible,
      well embedded into the intima. Neointimal growth and negative remodelling were
      the main operating mechanisms of restenosis. INTERPRETATION: This study shows
      that biodegradable magnesium stents can achieve an immediate angiographic result
      similar to the result of other metal stents and can be safely degraded after 4
      months. Modifications of stent characteristics with prolonged degradation and
      drug elution are currently in development.

PMID- 17544768
TI  - Efficacy of folic acid supplementation in stroke prevention: a meta-analysis.
AB  - BACKGROUND: The efficacy of treatments that lower homocysteine concentrations in
      reducing the risk of cardiovascular disease remains controversial. Our aim was to
      do a meta-analysis of relevant randomised trials to assess the efficacy of folic
      acid supplementation in the prevention of stroke. METHODS: We collected data from
      eight randomised trials of folic acid that had stroke reported as one of the
      endpoints. Relative risk (RR) was used as a measure of the effect of folic acid
      supplementation on the risk of stroke with a random effect model. The analysis
      was further stratified by factors that could affect the treatment effects.
      FINDINGS: Folic acid supplementation significantly reduced the risk of stroke by
      18% (RR 0.82, 95% CI 0.68-1.00; p=0.045). In the stratified analyses, a greater
      beneficial effect was seen in those trials with a treatment duration of more than
      36 months (0.71, 0.57-0.87; p=0.001), a decrease in the concentration of
      homocysteine of more than 20% (0.77, 0.63-0.94; p=0.012), no fortification or
      partly fortified grain (0.75, 0.62-0.91; p=0.003), and no history of stroke
      (0.75, 0.62-0.90; p=0.002). In the corresponding comparison groups, the estimated
      RRs were attenuated and insignificant. INTERPRETATION: Our findings indicate that
      folic acid supplementation can effectively reduce the risk of stroke in primary
      prevention.

PMID- 17544769
TI  - A girl with episodic abdominal pain.

PMID- 17544770
TI  - Physical abuse and neglect of children.
AB  - Child maltreatment includes physical abuse and neglect, and happens in all
      countries and cultures. Child maltreatment usually results from interactions
      between several risk factors (such as parental depression, stress, and social
      isolation). Physicians can incorporate methods to screen for risk factors into
      their usual appointments with the family. Detection of physical abuse is
      dependent on the doctor's ability to recognise suspicious injuries, such as
      bruising, bite marks, burns, bone fractures, or trauma to the head or abdomen.
      Neglect is the most common form of child maltreatment in the USA. It can be
      caused by insufficient parental knowledge; intentional negligence is rare.
      Suspected cases of child abuse should be well documented and reported to the
      appropriate public agency which should assess the situation and help to protect
      the child.

PMID- 17544771
TI  - Ventricular fibrillation during termination of pregnancy.

PMID- 17544772
TI  - Exploring the other side of biologically relevant chemical space: insights into
      carboxylic, sulfonic and phosphonic acid bioisosteric relationships.
AB  - Bioisosteric replacements have been widely and successfully applied to develop
      bioisosteric series of biologically active compounds in medicinal chemistry. In
      this work, the concept of bioisosterism is revisited using a novel approach based
      on charting the "other side" of biologically relevant chemical space. This space
      is composed by the ensemble of binding sites of protein structures. Explorations
      into the "other side" of biologically relevant chemical space are exploited to
      gain insight into the principles that rules molecular recognition and
      bioisosteric relationships of molecular fragments. We focused, in particular, on
      the construction of the "other side" of chemical space covered by binding sites
      of small molecules containing carboxylic, sulfonic, and phosphonic acidic groups.
      The analysis of differences in the occupation of that space by distinct types of
      binding sites unveils how evolution has worked in assessing principles that rule
      the selectivity of molecular recognition, and improves our knowledge on the
      molecular basis of bioisosteric relationships among carboxylic, sulfonic, and
      phosphonic acidic groups.

PMID- 17544773
TI  - The role of pharmaceutical companies in sponsored research.

PMID- 17544774
TI  - Natural course of intraocular pressure after cataract surgery with sodium
      hyaluronate 1% versus hydroxypropylmethylcellulose 2%.
AB  - PURPOSE: To investigate the natural course of intraocular pressure (IOP) after
      small-incision cataract surgery with sodium hyaluronate 1% versus
      hydroxypropylmethylcellulose 2%. DESIGN: Randomized clinical trial. PARTICIPANTS:
      Eighty eyes of 40 consecutive patients with bilateral age-related cataract.
      METHODS: The patients were assigned randomly to receive sodium hyaluronate 1% or
      hydroxypropylmethylcellulose 2% during cataract surgery in the first eye. The
      second eye received the other ophthalmic viscosurgical device. The IOP was
      measured preoperatively and 30 minutes; 1, 2, 3, 4, 6, 8, and 20 to 24 hours; and
      1 week postoperatively. MAIN OUTCOME MEASURE: Postoperative IOP increase.
      RESULTS: The highest mean IOP increase occurred at 8 hours postoperatively (5.3+/
      6.4 mmHg) in the sodium hyaluronate 1% group and at 2 hours postoperatively
      (7.8+/-6.1 mmHg) in the hydroxypropylmethylcellulose 2% group. Overall, the IOP
      increase was higher with hydroxypropylmethylcellulose 2% (P = 0.005). Intraocular
      pressure spikes to > or =30 mmHg occurred in 5 eyes (13%) in the sodium
      hyaluronate 1% group and 13 eyes (33%) in the hydroxypropylmethylcellulose 2%
      group. CONCLUSIONS: Sodium hyaluronate 1% and hydroxypropylmethylcellulose 2%
      caused significant IOP increases during the first 8 hours after cataract surgery.
      A single measurement at 6 hours postoperatively could detect all IOP spikes in
      the sodium hyaluronate 1% group. In the hydroxypropylmethylcellulose 2% group, a
      single measurement at 2 hours postoperatively could detect two thirds of IOP
      spikes.

PMID- 17544775
TI  - A case-control study of drug risk factors for age-related macular degeneration.
AB  - OBJECTIVE: To investigate the association between age-related macular
      degeneration (AMD) and exposure to antacids, antithyroids, thyroid hormones, and
      thiazide diuretics. DESIGN: Matched case-control study. PARTICIPANTS: Population
      based participants were selected from the United Kingdom General Practice
      Research Database. A total of 18,007 people with diagnosed AMD were compared with
      86 169 controls matched for age, gender, and general practice. METHODS:
      Conditional logistic regression was used to determine the association between
      exposure to each drug group of interest and a diagnosis of AMD, adjusting for
      relevant confounding variables. MAIN OUTCOME MEASURES: The primary outcome was
      the odds ratio for the association between exposure to antacids, antithyroids,
      thyroid hormones, or thiazide diuretics and AMD. Secondary analyses were
      conducted to assess the effect of recent exposure to the drugs of interest, the
      total number of prescriptions received, and restricting the data set to
      participants with more than 2 years of observation time. RESULTS: The crude odds
      ratios for association between any record of drug exposure and AMD were as
      follows: 1.34 (95% confidence interval [CI], 1.29-1.39) for antacids; 1.15 (95%
      CI, 0.92-1.44) for antithyroids; 1.34 (95% CI, 1.29-1.39) for thyroid hormones;
      and 1.13 (95% CI, 1.08-1.17) for thiazide diuretics. After adjusting for
      consultation rate, observation time, diabetes, heart failure, hyperlipidemia,
      cardiovascular drug use, atherosclerosis, hypertension, aspirin use, hormone
      replacement therapy use, body mass index, alcohol consumption, and smoking, the
      odds ratios reduced to: 1.06 (95% CI, 1.02-1.10) for antacids, 0.98 (95% CI, 0.78
      1.24) for antithyroids, 0.99 (95% CI, 0.92-1.06) for thyroid hormones, and 0.98
      (95% CI, 0.94-1.02) for thiazides. Secondary analyses were consistent with these
      findings for all 4 drug categories. CONCLUSIONS: No association was detected
      between short- and medium-term use of antithyroids, thyroid hormones, and
      thiazide diuretics and the risk of AMD. Short- and medium-term use of antacids
      seems to be associated with a small increase in the risk of this disease.
      However, this increased risk is likely the result of residual confounding by
      smoking or uncontrolled confounding resulting from socioeconomic status. No
      conclusions could be drawn regarding longer-term use of each drug category.

PMID- 17544777
TI  - Mortality in patients with branch retinal vein occlusion.
AB  - PURPOSE: To assess the impact of branch retinal vein occlusion (BRVO), a
      condition related to arteriolar wall thickening, as a prognostic marker of
      mortality. DESIGN: Long-term follow-up study comparing cases with background
      population. PARTICIPANTS: Patients diagnosed with BRVO. METHODS: Diagnosis of
      BRVO confirmed by fundus photographic records including color diapositives and
      fluorescein angiograms. MAIN OUTCOME MEASURES: Observed and expected numbers of
      deaths determined from comprehensive civic records in cases compared with the
      background population (5.4 million). RESULTS: Branch retinal vein occlusion was
      found in 329 patients (173 women, 156 men) born between 1902 and 1956, who were
      39 to 91 years old when diagnosed between 1973 and 1998. Follow-up was concluded
      on July 8, 2004, when 144 deaths were recorded in patients (74 women, 70 men),
      compared with an expected number of 145.5 deaths in the background population
      (standardized mortality rate, 0.99; 95% confidence interval, 0.84-1.16).
      Stratified analyses revealed no significant effect of age, gender, or time of
      diagnosis. CONCLUSIONS: In this study of 329 patients with BRVO, we found no
      significant difference in mortality between patients and the background
      population. An association between BRVO and cardiovascular/cerebrovascular risk
      factors has previously been documented in cross-sectional studies. The
      contrasting outcome in this longitudinal study may have been influenced by
      interventions instituted after the diagnosis of BRVO was made and by preferential
      survival before the diagnosis of BRVO of the more fit patients with the necessary
      precursor condition of having arteriovenous nicking, which is more prevalent in
      subjects with diabetes and hypertension.

PMID- 17544776
TI  - Verteporfin therapy and intravitreal bevacizumab combined and alone in choroidal
      neovascularization due to age-related macular degeneration.
AB  - OBJECTIVE: To evaluate the efficacy and safety of photodynamic therapy (PDT) with
      verteporfin combined with intravitreal bevacizumab in choroidal
      neovascularization (CNV) owing to age-related macular degeneration (AMD) in
      comparison with individual monotherapies used as controls. DESIGN: Randomized
      controlled pilot clinical trial. PARTICIPANTS: Males or females, aged > or =50
      years, with minimally classic or occult CNV owing to AMD in at least 1 eye that
      had never been treated previously. METHODS: One hundred sixty-five eyes in 165
      subjects (53 males, 112 females) aged between 60 and 87 years (mean [standard
      deviation]: 75.7 [6.0] years) were randomly assigned to receive either a single
      PDT session with verteporfin (PDT group; n = 55), or a single administration of
      intravitreal bevacizumab (1.25 mg; BEV group; n = 55), or their combination (COMB
      group; n = 55). In the COMB group, bevacizumab was administered within 1 hour of
      PDT. Subjects were followed up at 1 and 3 months after treatment. Ophthalmic
      evaluations including optical coherence tomography, fluorescein angiography, and
      visual acuity (VA) and central foveal thickness (CFT) measurements were performed
      at each visit. MAIN OUTCOME MEASURES: Changes from baseline in best-corrected VA
      and CFT measured at 1- and 3-month follow-up visits. RESULTS: One hundred fifty
      six subjects (54 BEV, 50 PDT, and 52 COMB) completed the study. At the 3-month
      follow-up, significant improvements in best-corrected VA were observed in the BEV
      and COMB groups (0.079 and 0.223 logarithm of the minimum angle of resolution
      [logMAR], respectively; P<0.0001 for both). In the PDT group, a slight worsening
      was noted. Significant reductions of CFT were observed in the 3 groups (-34.0
      microm [BEV], -59.6 microm [COMB], and -50.5 microm [PDT]; P<0.0001 for all). At
      the 1-month follow-up, 46 subjects (16 BEV, 29 COMB, and 1 PDT) had an
      improvement >0.2 logMAR in best-corrected VA; at 3-month follow-up, this
      improvement persisted in 23 subjects (1 BEV, 22 COMB, and 0 PDT). CONCLUSIONS:
      Significant improvements in best-corrected VA after 1 month and their maintenance
      over a 3-month period were observed after verteporfin PDT combined with
      intravitreal bevacizumab. These results should be confirmed in larger and long
      term prospective randomized trials.

PMID- 17544778
TI  - Randomized trial of peribulbar triamcinolone acetonide with and without focal
      photocoagulation for mild diabetic macular edema: a pilot study.
AB  - OBJECTIVE: To provide pilot data on the safety and efficacy of anterior and
      posterior sub-Tenon injections of triamcinolone either alone or in combination
      with focal photocoagulation in the treatment of mild diabetic macular edema
      (DME). DESIGN: Prospective, phase II, multicenter, randomized clinical trial.
      PARTICIPANTS: One hundred nine patients (129 eyes) with mild DME and visual
      acuity 20/40 or better. METHODS: The participants were assigned randomly to
      receive either focal photocoagulation (n = 38), a 20-mg anterior sub-Tenon
      injection of triamcinolone (n = 23), a 20-mg anterior sub-Tenon injection
      followed by focal photocoagulation after 4 weeks (n = 25), a 40-mg posterior sub
      Tenon injection of triamcinolone (n = 21), or a 40-mg posterior sub-Tenon
      injection followed by focal photocoagulation after 4 weeks (n = 22). Follow-up
      visits were performed at 4, 8, 17, and 34 weeks. MAIN OUTCOME MEASURES: Change in
      visual acuity and retinal thickness measured with optical coherence tomography
      (OCT). RESULTS: At baseline, mean visual acuity in the study eyes was 20/25 and
      mean OCT central subfield thickness was 328 mum. Changes in retinal thickening
      and in visual acuity were not significantly different among the 5 groups at 34
      weeks (P = 0.46 and P = 0.94, respectively). There was a suggestion of a greater
      proportion of eyes having a central subfield thickness less than 250 mum at 17
      weeks when the peribulbar triamcinolone was combined with focal photocoagulation.
      Elevated intraocular pressure and ptosis were adverse effects attributable to the
      injections. CONCLUSIONS: In cases of DME with good visual acuity, peribulbar
      triamcinolone, with or without focal photocoagulation, is unlikely to be of
      substantial benefit. Based on these results, a phase III trial to evaluate the
      benefit of these treatments for mild DME is not warranted.

PMID- 17544779
TI  - Outcomes of 77 consecutive cases of 23-gauge transconjunctival vitrectomy surgery
      for posterior segment disease.
AB  - PURPOSE: To describe the initial experience, effectiveness, and safety profile of
      23-gauge instrumentation for a variety of vitreoretinal conditions. DESIGN:
      Single-center, retrospective, noncomparative, consecutive interventional case
      series. PARTICIPANTS: Seventy-seven eyes of consecutive patients who underwent 23
      gauge transconjunctival vitrectomy surgery by a single surgeon at the Manhattan
      Eye, Ear, and Throat Hospital from October 2004 through October 2005.
      INTERVENTION: All patients underwent 3-port 23-gauge vitrectomy using Dutch
      Ophthalmic Research Corporation instrumentation and an Alcon Accuris Vitrector.
      MAIN OUTCOME MEASURES: Postoperative visual acuity at months 1 and 3,
      intraoperative and postoperative complications, and operative time. RESULTS: Mean
      acuity improved from 20/190 at baseline to 20/108 (P<0.0001) and 20/74 (P<0.0001)
      at months 1 and 3, respectively. By diagnosis, patients with epiretinal membrane
      (n = 20) improved from 20/124 to 20/93 (P = 0.0046), macular hole (n = 18) from
      20/174 to 20/57 (P = 0.0007), rhegmatogenous retinal detachment (RD) (n = 14)
      from 20/248 to 20/51 (P = 0.0004), tractional RD (n = 12) from 20/175 to 20/62 (P
      = 0.0159), nonclearing vitreous hemorrhage (n = 12) from 20/1345 to 20/189 (P =
      0.0004), vitreomacular traction (n = 4) from 20/145 to 20/124 (P = 0.7525), and
      retained lens fragments (n = 4) from 20/308 to 20/140 (P = 0.0972). One patient
      who underwent diagnostic vitrectomy had stable 20/50 acuity. Two patients had
      hypotony on postoperative day 1, 1 patient required a sutured sclerotomy
      intraoperatively, and no patients developed choroidal effusions. No
      intraoperative tears were noted. Surgical times collected on 17 patients during
      the final month of the study demonstrated a mean opening time (range) of 103
      seconds (70-162), mean closing time of 75 seconds (17-470), and net operating
      time of 24.1 minutes (7.1-74.6). CONCLUSIONS: Twenty-three-gauge instrumentation
      is effective for a variety of vitreoretinal surgical indications. The safety
      profile compared favorably with published rates for 25-gauge systems.

PMID- 17544780
TI  - Accommodation during static retinal imaging with a confocal scanning laser
      ophthalmoscope.
AB  - PURPOSE: Accommodation of the eye can adversely affect optical tomography of the
      retina using a confocal scanning laser ophthalmoscope (cSLO). This study measured
      the dynamic accommodative response of young adult eyes while acquiring static
      retinal images with a cSLO without cycloplegia and also examined whether a
      scanned fixation target improves stability of accommodation. DESIGN: Experimental
      study. PARTICIPANTS: Four eyes of 4 controls whose ages ranged from 24 to 35
      years. METHODS: Dynamic accommodation was measured by an infrared autorefractor
      during static cSLO imaging with a fixation target, without a target, while in
      darkness, and while viewing a Snellen chart at 20-feet distance. MAIN OUTCOME
      MEASURES: Mean accommodation across viewing conditions and rate of change of
      accommodation (velocity). RESULTS: Accommodation significantly increased in
      amplitude and in variability during imaging with the cSLO. Average peak velocity
      of accommodation was 1.37 diopters (D)/second, with a maximum of 2.27 D/second.
      Presenting a fixation target in the cSLO did not decrease accommodation but
      increased accommodation velocity in 3 of 4 subjects. CONCLUSION: Accommodation
      dynamically changes during acquisition of retinal images with a cSLO. Concurrent
      scanning of a visible target did not improve stability of accommodation reliably.
      Potential factors affecting accommodation include depth of focus (DOF), use of
      monochromatic stimuli, and nearby cues. Using the model eye, the error induced by
      accommodation is about 491 mum/second, with a maximum of 813 mum/second. In terms
      of the time to acquire individual optical sections, these estimates are
      consistent with previous reports of increased variability of topographic
      measurements in nondilated eyes.

PMID- 17544781
TI  - Hand washing.

PMID- 17544782
TI  - Post-LASIK ectasia.

PMID- 17544783
TI  - Trabeculectomy with mitomycin C.

PMID- 17544785
TI  - Rheumatic disease and scleritis.

PMID- 17544786
TI  - Periocular and orbital amyloidosis.

PMID- 17544787
TI  - Fundus autofluorescence.

PMID- 17544790
TI  - Vitelliform macular dystrophy.

PMID- 17544792
TI  - Giant cell arteritis.

PMID- 17544793
TI  - Intraocular lymphoma.

PMID- 17544794
TI  - Orbital lymphoma, amyloid, and bone.

PMID- 17544795
TI  - Posttraumatic stress.

PMID- 17544797
TI  - CIDE-A gene expression is decreased in white adipose tissue of growth hormone
      receptor/binding protein gene disrupted mice and with high-fat feeding of normal
      mice.
AB  - Growth hormone's (GH) lipolytic activity in white adipose tissue (WAT) results in
      decreased body fat in giant GH transgenic mice and increased subcutaneous fat in
      dwarf growth hormone receptor/binding protein gene-disrupted mice (GHR -/-). We
      therefore hypothesized that GH action would affect expression of CIDE-A (cell
      death-inducing DFF45-like effector-A), a protein found in white adipose tissue
      (WAT) and involved in lipid metabolism. CIDE-A RNA levels were determined in
      subcutaneous, retroperitoneal and epididymal adipose tissue isolated from wild
      type and GHR -/- mice. The adipose tissue was also analyzed for adipocyte size.
      We determined that the lack of GH action has depot-specific effects on the levels
      of CIDE-A RNA and affected adipocyte cell size. CIDE-A expression is
      significantly reduced in GHR -/- subcutaneous fat compared to wild-type but is
      not altered in retroperitoneal or epididymal fat. Likewise, adipocytes are
      significantly enlarged in GHR -/- subcutaneous adipose tissue relative wild-type
      mice. A high-fat diet also influenced the level of CIDE-A RNA in mouse adipose
      tissue. The high-fat diet significantly reduced CIDE-A expression in wild-type
      subcutaneous fat but did not alter CIDE-A expression in subcutaneous fat of GHR 
      /- mice. The diet also reduced CIDE-A expression in wild-type retroperitoneal fat
      but the levels of CIDE-A in epididymal fat were unchanged. In contrast, the high
      fat diet reduced CIDE-A expression in both retroperitoneal and epididymal fat of
      GHR -/- mice. These data demonstrate that CIDE-A levels are reduced in two
      different mouse models of obesity and this reduction may contribute to altered
      lipid metabolism.

PMID- 17544798
TI  - Examination of an inducible expression system for limiting iron availability
      during Chlamydia trachomatis infection.
AB  - The obligate intracellular bacterium Chlamydia trachomatis requires iron in order
      to complete its developmental cycle. Addition of an iron-chelating drug, Desferal
      (deferoxamine mesylate), to infected cell culture causes Chlamydia to enter
      persistence. Here, we explore the ability of a stably-transfected cell line with
      inducible over-expression of the eukaryotic iron efflux protein ferroportin to
      starve C. trachomatis serovar E for iron. Ferroportin-induced iron removal is
      perhaps a more direct method of removing iron from the intracellular compartment
      versus exposure to an exogenous chemical chelator. Following induction,
      ferroportin-green fluorescent protein (Fpn-GFP) was detected in the plasma
      membrane, and cells expressing Fpn-GFP remained viable throughout the timescale
      required for Chlamydia to complete its developmental cycle. Following Fpn-GFP
      induction in infected cells, chlamydial infectivity remained unchanged,
      indicating chlamydiae were not in persistence. Ferritin levels indicate only a
      small decrease in cellular iron following Fpn-GFP expression relative to cultures
      exposed to Desferal. These data indicate that expression of Fpn-GFP in chlamydiae
      infected cells is not capable of reducing iron below the threshold concentration
      needed to cause chlamydiae to enter persistence.

PMID- 17544799
TI  - Autoreactive antibodies are present in sheep with Johne's disease and cross-react
      with Mycobacterium avium subsp. paratuberculosis antigens.
AB  - Mycobacterial infection has been linked to the generation of autoantibodies,
      including anti-neutrophil cytoplasmic autoantibodies (ANCA), in clinical studies
      and small animal models. In an attempt to identify antibodies that react with
      both self and mycobacterial antigens in naturally infected ruminants, we
      generated a phage display library comprising single chain antibody fragments
      (scFv) from sheep with Johne's disease (JD). The library was screened
      simultaneously against ovine small intestinal tissue and Mycobacterium avium
      subsp. paratuberculosis (MAP). A clone (termed AutoH1) reacted strongly with host
      tissue and MAP, recognizing a proteinase-susceptible 32 kDa determinant in ovine
      gut tissues and lymphatics, and in blood granulocytes but not mononuclear cells.
      In granulocytes, binding was to cytoplasmic granules and cell membranes; in MAP,
      AutoH1 bound bacterial cell wall determinants. We further identified a synthetic
      peptide sequence recognized by AutoH1, using this to generate a carrier:peptide
      fusion protein (paH1). Sera of normal and JD sheep were screened for AutoH1-like
      autoantibody activity; 7/11 JD animals showed autoreactivity that could be
      blocked by paH1, while 0/21 normal animals showed no such serological reactivity.
      It is possible that the severe pathology observed in ruminant JD may have an
      autoimmune component, possibly due to ANCA-type binding; this remains to be
      further investigated.

PMID- 17544800
TI  - IL-10 producing CD8+ T cells in human infection with Leishmania guyanensis.
AB  - Cytokines are increasingly recognized as important components of the cellular
      immune responses to intracellular pathogens. In this study, we analyzed the
      production of TGF-beta, IL-10 and IFN-gamma by PBMC of unexposed naive subjects
      and LCL patients after stimulation with live Leishmania guyanensis (L.g.). We
      demonstrated that IFN-gamma is produced in controls and LCL patients, IL-10 only
      in LCL patients and TGF-beta only in naive subjects. Furthermore, in naive
      subjects, neutralization of TGF-beta induced IL-10 production. IL-10 produced in
      naive subjects when TGF-beta is neutralized or in LCL patients did not modify the
      IFN-gamma production but inhibit reactive nitrogen species production. Analysis
      of the phenotype of IL-10 producing cells in naive subjects when TGF-beta is
      neutralized clearly showed that they are memory CD45RA- CD8+ T cells. In LCL
      patients, IL-10 producing cells are both CD45RA- CD4 and CD8+ T cells. The role
      of these IL-10 producing CD8+ T cells in the development of the diseases should
      be carefully evaluated.

PMID- 17544801
TI  - Epithelial membrane protein 2 modulates infectivity of Chlamydia muridarum
      (MoPn).
AB  - Chlamydiae are bacterial pathogens which have evolved efficient strategies to
      enter, replicate, and survive inside host epithelial cells, resulting in acute
      and chronic diseases in humans and other animals. Several candidate molecules in
      the host receptor complex have been identified, but the precise mechanisms of
      infection have not been elucidated. Epithelial membrane protein-2 (EMP2), a 4
      transmembrane protein, is highly expressed in epithelial cells in sites of
      chlamydial infections. Here we show that infectivity of the Chlamydia muridarum
      (MoPn) is associated with host cellular expression of EMP2 in multiple cell
      lines. Recombinant knockdown of EMP2 impairs infectivity, whereas infectivity is
      augmented in cells recombinantly modified to over-express EMP2. An epithelial
      cell line without native expression of EMP2 is relatively resistant to MoPn
      infection, whereas infectivity is markedly increased by recombinant expression of
      EMP2 in that cell line. Blockade of surface EMP2 using a specific anti-EMP2
      antibody significantly reduces chlamydial infection efficiency. In addition, MoPn
      infectivity as measured in the EMP2 overexpressing cell line is not heparin
      dependent, suggesting a possible role for EMP2 in the non-reversible phase of
      early infection. These findings identify EMP2 as a candidate host protein
      involved in infection of C. muridarum (MoPn).

PMID- 17544802
TI  - Schistosoma mansoni infection enhances host portal vein contraction: role of
      potassium channels and p38 MAP kinase.
AB  - Murine Schistosoma mansoni infection is related to an increased contraction of
      portal vein in response to 5-hydroxytryptamine (5-HT). The present study
      addressed a putative alteration of ion channels and enzymes involved in vascular
      contraction. In control group, either inhibition of K+ channels sensitive to ATP
      (K(ATP)) or Ca2+ (BK(Ca)) increased 5-HT-induced contraction, but the same did
      not occur in infected mice. On the other hand, inhibition of p38 MAP kinase
      markedly decreased the vascular contraction to 5-HT in the infected mice with
      minor effects in the control group. Accordingly, we observed a higher density of
      phospho-p38 MAP kinase, that refers to the fully active state of the enzyme, in
      portal veins from infected mice as compared to control animals. These results
      suggest that the reduced function of K(ATP) and BK(Ca) channels along with an
      increased contribution of p38 MAP kinase contribute to the increased contraction
      of portal veins to 5-HT observed in murine schistosomiasis.

PMID- 17544803
TI  - Upregulation of capsule enables Streptococcus pyogenes to evade immune
      recognition by antigen-specific antibodies directed to the G-related alpha2
      macroglobulin-binding protein GRAB located on the bacterial surface.
AB  - One of the major problems associated with the development of a vaccine against
      Streptococcus pyogenes is the ability of this pathogen to escape recognition by
      antibodies directed against conserved surface-associated determinants and to
      establish infection in the setting of an acquired immune response. Identification
      of the mechanism(s) used by S. pyogenes to avoid recognition by antigen-specific
      antibodies and escape killing in blood was the focus of this study. We showed
      here that S. pyogenes was capable of surviving in human blood containing high
      levels of antibodies directed against the G-related alpha2-macroglobulin-binding
      protein GRAB, a highly conserved bacterial surface protein. S. pyogenes
      upregulated the hyaluronic acid capsule production during incubation with human
      blood, suggesting that the capsule may structurally minimize antibody access to
      protein GRAB. This hypothesis was confirmed by the ability of anti-GRAB
      antibodies to promote opsonophagocytosis of a capsule-deficient mutant of S.
      pyogenes but not of the encapsulated wild-type strain. Capsule upregulation and
      protection of S. pyogenes from opsonophagocytosis in the presence of anti-GRAB
      antibodies was also observed in a murine model of streptococcal infection. Thus,
      masking of surface immunogenic determinants by the hyaluronic acid capsule may
      constitute a novel mechanism of S. pyogenes for evasion of antigen-specific
      antibodies.

PMID- 17544804
TI  - Characterization of humoral and cellular immune responses in cynomolgus macaques
      upon primary and subsequent heterologous infections with dengue viruses.
AB  - Since studying the pathogenesis of dengue virus associated disease in humans has
      several limitations, an appropriate animal model is needed. Therefore, we
      investigated kinetics of viremia as well as humoral and cellular immune
      responses, after primary, secondary and tertiary heterologous dengue virus
      infections in cynomolgus macaques: these parameters were largely similar to those
      observed in natural human infection upon primary infection. Both antibody and T
      cell responses measured were largely cross-reactive. Upon secondary infection
      with a heterologous virus serotype, T-cell responses specific for the primary
      infecting serotype were more pronounced, especially when the immune system was
      primed with dengue 1 virus. Measurement of transcription levels of pro- and anti
      inflammatory cytokines in white blood cells upon primary and secondary infection
      generally showed a balanced response. In addition, a region of the NS2A protein
      of dengue viruses was identified that induces T-cell responses in macaques.

PMID- 17544805
TI  - Metabolism of nitric oxide by Neisseria meningitidis modifies release of NO
      regulated cytokines and chemokines by human macrophages.
AB  - Macrophages produce nitric oxide (NO) via the inducible nitric oxide synthase as
      part of a successful response to infection. The gene norB of Neisseria
      meningitidis encodes a NO reductase which enables utilization and consumption of
      NO during microaerobic respiration and confers resistance to nitrosative stress
      related killing by human monocyte-derived macrophages (MDM). In this study we
      confirmed that NO regulates cytokine and chemokine release by resting MDM:
      accumulation of TNF-alpha, IL-12, IL-10, CCL5 (RANTES) and CXCL8 (IL-8) in MDM
      supernatants was significantly modified by the NO-donor S-nitroso-N-penicillamine
      (SNAP). Using a protein array, infection of MDM with N. meningitidis was shown to
      be associated with secretion of a wide range of cytokines and chemokines. To test
      whether NO metabolism by N. meningitidis modifies release of NO-regulated
      cytokines, we infected MDM with wild-type organisms and an isogenic norB strain.
      Resulting expression of the cytokines TNF-alpha and IL-12, and the chemokine
      CXCL8 was increased and production of the cytokine IL-10 and the chemokine CCL5
      was decreased in norB-infected MDM, in comparison to wild-type. Addition of SNAP
      to cultures infected with wild-type mimicked the effect observed in cultures
      infected with the norB mutant. In conclusion, NorB-catalysed removal of NO
      modifies cellular release of NO-regulated cytokines and chemokines.

PMID- 17544806
TI  - Reduction of bacterial adhesion on ion-implanted stainless steel surfaces.
AB  - The high incidence of infections caused by the use of biomedical devices has a
      severe impact on human health. An approach to reduce the complications is to
      modify the surface properties of biomedical devices. In this paper, stainless
      steel disks were implanted with N(+), O(+) and SiF(3)(+), respectively, by an ion
      implantation technique. The surface properties of the ion-implanted surfaces were
      characterized, including their surface chemical composition, roughness,
      topography, wettability and surface energy. Bacterial adhesion of Staphylococcus
      epidermidis and Staphylococcus aureus, which frequently cause medical device
      associated infections was evaluated. The experimental results showed that these
      implanted stainless steels, particularly SiF(3)(+) implanted stainless steel
      performed much better than untreated stainless steel control on reducing
      bacterial attachment.

PMID- 17544807
TI  - Unusual compulsive behaviors primarily related to dopamine agonist therapy in
      Parkinson's disease and multiple system atrophy.
AB  - Unusual compulsive behaviors (weighing, card and video game playing, fishing,
      gardening, intense interest in established hobbies, locking and unlocking doors,
      repetitive dressing and undressing) occurred in relation to dopamine agonist
      therapy (six patients) and levodopa therapy (one patient) in seven patients with
      parkinsonism (seven Parkinson's disease, one multiple system atrophy). These
      behaviors occurred in tandem with pathological gambling, hypersexuality,
      compulsive eating, compulsive shopping or punding in six of the seven cases.
      Obsessive thoughts were present in one patient, with no prior history of
      obsessive-compulsive disorder. The simultaneous occurrence of these
      phenomenologically distinct behaviors in this group of patients suggests that a
      broad spectrum of psychopathology may occur in this context and should be
      monitored for in routine neurological practice.

PMID- 17544808
TI  - Proceedings of the 6th International Workshop on the First Component of
      Complement C1 and Collectins, Seeheim, Germany, June 2006.

PMID- 17544809
TI  - The phylogeny of the complement system and the origins of the classical pathway.
AB  - The origins of the complement system have now been traced to near to the
      beginnings of multi-cellular animal life. Most of the evidence points to the
      earliest activation mechanism having been more similar to the lectin pathway than
      to the alternative pathway. C1q, the immunoglobulin recognition molecule of the
      classical pathway of the vertebrates, has now been shown to predate the
      development of antibody as it has been found in the lamprey, a jawless fish that
      lacks an acquired immune system. In this species, C1q acts as a lectin that binds
      MASPs and activates the C3/C4-like thioester protein of the lamprey complement
      system. The classical pathway can, therefore, be regarded as a specialised arm of
      the lectin pathway in which the specificity of C1q for carbohydrate has been
      recruited to recognise the Fc region of immunoglobulin.

PMID- 17544810
TI  - The regulatory roles of C1q.
AB  - C1q binds to immune complexes to elicit complement-dependent microbial killing
      and enhance phagocytosis. Besides this classical role, C1q also opsonizes
      apoptotic cells for clearance by phagocytes. C1q deficiency increases
      susceptibility to microbial infections and is also associated with elevated
      autoimmunity as characterized by increased apoptotic bodies in tissues. Most
      complement proteins are of liver origin, but C1q is predominantly synthesized by
      peripheral tissue macrophages and dendritic cells. Besides being found in the
      blood, C1q has also been found deposited in extracellular tissues around these
      cells. In vitro, immobilized C1q inhibits monocyte, macrophage and T-cell
      production of inflammatory cytokines. It also regulates T-cell activation.
      Therefore, mounting evidence suggest a major regulatory role for C1q in
      inflammation and autoimmunity.

PMID- 17544811
TI  - C1q and its growing family.
AB  - C1q is the target recognition protein of the classical complement pathway and a
      major connecting link between innate and acquired immunity. As a charge pattern
      recognition molecule of innate immunity, C1q can engage a broad range of self and
      non-self ligands via its heterotrimeric globular (gC1q) domain and thus trigger
      the classical pathway. The trimeric gC1q signature domain has been identified in
      a variety of non-complement proteins that can be grouped together as a C1q
      family. The X-ray crystal structures of the gC1q domain of a few members of the
      C1q family reveal a compact jelly-roll beta-sandwich fold similar to that of the
      multifunctional tumor necrosis factor (TNF) ligand family, hence the C1q and TNF
      superfamily. This review is an update on the structural and functional aspects of
      the gC1q domain of human C1q. We also mention the diverse range of proteins that
      utilize a gC1q domain in order to reflect on its importance as a versatile
      scaffold to support a variety of functions.

PMID- 17544812
TI  - Serine proteases of the classical and lectin pathways: similarities and
      differences.
AB  - C1r, C1s, MBL-associated serine protease (MASP)-1, MASP-2 and MASP-3 are mosaic
      serine proteases of the classical and lectin pathways of complement. They form a
      family of enzymes with identical domain organization and similar overall
      structure, but with different enzymatic properties. MASP-2 of the lectin pathway
      can autoactivate and cleave C4 and C2 components. In the classical pathway two
      enzymes mediate these functions: C1r autoactivates and activates C1s, while C1s
      cleaves C4 and C2. The substrate specificity and the biological function of MASP
      1 and MASP-3 have not yet been completely resolved. MASP-1 can autoactivate and
      the activated MASP-1 has more relaxed substrate specificity than the other
      members of the family. It was demonstrated that MASP-1 can specifically cleave
      C2, C3 and fibrinogen, but the physiological relevance of these findings has to
      be proved. We do not know how MASP-3 becomes activated and its biological
      function is also not clear. In this review, we will summarize current knowledge
      about the structure and function of these proteases. Special emphasis will be
      laid on the specificity, autoactivation and evolution of these enzymes.

PMID- 17544813
TI  - Assembly of C1 and the MBL- and ficolin-MASP complexes: structural insights.
AB  - The classical pathway C1 complex, and the MBL-MASP and ficolin-MASP complexes
      involved in activation of the lectin pathway have several features in common.
      Both types of complexes are assembled from two subunits: an oligomeric
      recognition protein (C1q, MBL, L-, H- or M-ficolin), and a protease component,
      which is either a tetramer (C1s-C1r-C1r-C1s) or a dimer ((MASP)(2)). Recent
      functional and 3-D structural investigations have revealed that C1r/C1s and the
      MASPs associate through a common mechanism involving their N-terminal CUB1-EGF
      region. In contrast, the C1s-C1r-C1r-C1s tetramer and the (MASP)(2) dimers appear
      to have evolved distinct strategies to associate with their partner proteins. The
      purpose of this article is to review these recent advances.

PMID- 17544815
TI  - New perspectives on mannan-binding lectin-mediated complement activation.
AB  - The complement system is an important part of the innate immune system, mediating
      several major effector functions and modulating adaptive immune responses. Three
      complement activation pathways exist: the classical pathway (CP), the alternative
      pathway (AP), and the lectin pathway (LP). The LP is the most recently
      discovered, and least characterized. The CP and the LP are generally viewed as
      working through the generation of the C3 convertase, C4bC2b, and are here
      referred to as the "standard" pathways. In addition to the standard CP and LP, so
      called bypass pathways have also been reported, allowing C3 activation in the
      absence of components otherwise believed critical. The classical bypass pathways
      are dependent on C1 and components of the AP. A recent study has shown the
      existence also of a lectin bypass pathway dependent on mannan-binding lectin
      (MBL) and AP components. The emerging picture of the complement system is more
      that of a small "scale-free" network where C3 acts as the main hub, than that of
      three linear pathways converging in a common terminal pathway.

PMID- 17544814
TI  - Interactions between mannose-binding lectin and MASPs during complement
      activation by the lectin pathway.
AB  - The lectin pathway of complement performs a key role within the immune system by
      recognising pathogens through patterns of sugar moieties displayed on their cell
      surfaces and neutralising them via an antibody-independent reaction cascade.
      While particularly important during early childhood before the adaptive immune
      system is established, or when adaptive immunity is compromised, it has a
      protective function throughout life, neutralising invading pathogens directly and
      helping to stimulate and direct an effective immune response. Complement
      activation is initiated when complexes comprising mannose-binding lectin (MBL) or
      serum ficolins and MBL-associated serine protease-2 (MASP-2) bind to pathogens.
      Binding induces conformational changes in these complexes, leading to
      autoactivation of the MASPs, which in turn activate the downstream reaction
      cascade. A major goal in complement research is to understand the molecular
      events that trigger complement activation. Over the last few years, structure
      function studies have improved our knowledge of the way in which MBL binds to
      MASPs by defining the portions of these proteins that interact and by solving the
      structures of key protein fragments. In this review, I will summarise the main
      findings of these studies and describe current theories to explain how the
      components combine to initiate the reaction cascade.

PMID- 17544816
TI  - C1 inhibitor: biologic activities that are independent of protease inhibition.
AB  - C1 inhibitor therapy improves outcome in several animal models of inflammatory
      disease. These include sepsis and Gram negative endotoxin shock, vascular leak
      syndromes, hyperacute transplant rejection, and ischemia-reperfusion injury.
      Furthermore, some data suggest a beneficial effect in human inflammatory disease.
      In many inflammatory conditions, complement system activation plays a role in
      pathogenesis. The contact system also very likely is involved in mediation of
      damage in inflammatory disease. Therefore, the beneficial effect of C1 inhibitor
      has been assumed to result from inhibition of one or both of these systems. Over
      the past several years, several other potential anti-inflammatory effects of C1
      inhibitor have been described. These effects do not appear to require protease
      inhibition and depend on non-covalent interactions with other proteins, cell
      surfaces or lipids. In the first, C1 inhibitor binds to a variety of
      extracellular matrix components including type IV collagen, laminin, entactin and
      fibrinogen. The biologic role of these reactions is unclear, but they may serve
      to concentrate C1 inhibitor at extravascular inflammatory sites. The second is a
      non-covalent interaction with C3b that results in inhibition of formation of the
      alternative pathway C3 convertase, a function analogous to that of factor H. The
      third is an interaction with E and P selectins on endothelial cells that is
      mediated by the Lewis(x) tetrasaccharides that are expressed on C1 inhibitor.
      These interactions result in suppression of leukocyte rolling and transmigration.
      The fourth interaction is the binding of C1 inhibitor to Gram negative bacterial
      endotoxin that results in suppression of endotoxin shock by interference with the
      interaction of endotoxin with its receptor complex on macrophages. Lastly, C1
      inhibitor binds directly to Gram negative bacteria, which leads to suppression of
      the development of sepsis, as demonstrated in the cecal ligation and puncture
      model. These observations suggest that C1 inhibitor is a multi-faceted anti
      inflammatory protein that exerts its effects through a variety of mechanisms
      including both protease inhibition and several different non-covalent
      interactions that are unrelated to protease inhibition.

PMID- 17544817
TI  - The deficiency of C1 inhibitor and its treatment.
AB  - In this article, we review the traditional therapies of hereditary angioedema
      (HAE) that have been used for several years. Some of these therapies were
      proposed before the definition of the underlying defect and the understanding of
      the pathogenesis of the disease. We also describe new compounds under
      investigation at present as potential therapies for HAE. Two of these new
      therapies (a plasma-kallikrein inhibitor and a bradykinin B(2)-receptor
      antagonist) have been developed based on the understanding that the pathogenesis
      of symptoms was mainly due to kallikrein activation and bradykinin release.

PMID- 17544819
TI  - The alpha2beta1 integrin: a novel collectin/C1q receptor.
AB  - Our laboratory focuses on the alpha2beta1 integrin, a receptor for a number of
      matrix and non-matrix ligands, including collagens, laminins, decorin, E
      cadherin, matrix metalloproteinase-1 (MMP-1), endorepellin, and several viruses.
      The alpha2beta1 integrin is expressed on numerous different cell types, including
      epithelial cells, endothelial cells, fibroblasts, and hematopoietic elements,
      including platelets and specific subsets of leukocytes. Although alpha2beta1
      integrin expression is widespread, it is not ubiquitous. Rather, it is expressed
      in a differentiation-dependent and activation-dependent manner. Interactions
      between the alpha2beta1 integrin and extracellular matrix ligands have been
      implicated in important biological processes including inflammation and immunity.
      Studies from a number of laboratories have demonstrated a role for the
      alpha2beta1 integrin during the immune response. Our laboratory generated an
      alpha2beta1 integrin-deficient mouse to define the role of the alpha2beta1
      integrin in vivo. Our studies demonstrated that the alpha2-null mice have a
      profound defect in the innate immune response. We have recently reported the
      identification of a novel family of ligands for the alpha2beta1 integrin, which
      include C1q and the collectins. The goal of this article is to review the
      important role that the interaction between the alpha2beta1 integrin and C1q
      plays in the innate immune response. The identification of C1q and the collectins
      as ligands for the alpha2beta1 integrin suggests that the integrin may play
      important roles in a number of immunological responses.

PMID- 17544818
TI  - The contribution of gC1qR/p33 in infection and inflammation.
AB  - Human gC1qR/p33 is a multi-compartmental and multi-functional cellular protein
      expressed on a wide range of tissues and cell types including lymphocytes,
      endothelial cells, dendritic cells, and platelets. Although originally isolated
      as a receptor for C1q by virtue of its affinity (K(d)=15-50 nM), and specificity
      for the globular heads of this molecule, a large body of evidence has now been
      accumulated which shows that in addition to C1q, gC1qR can serve as a receptor
      for diverse proinflammatory ligands including proteins of the plasma kinin
      forming system, most notably high molecular weight kininogen (HK; K(d)=9 nM). In
      addition, gC1qR has been reported to recognize and bind a number of functional
      antigens of viral and bacterial origin. It is its ability to interact with
      microbial antigens and its potential to serve as a cellular protein for bacterial
      attachment and/or entry that has been the focus of our laboratory in the past few
      years. On the surface of activated platelets, gC1qR has been shown to serve as a
      binding site for Staphylococcus aureus and this binding is mediated by protein A.
      Since the binding of S. aureus to platelets is postulated to play a major role in
      the pathogenesis of endocarditis, gC1qR may provide a suitable surface for the
      initial adhesion of the bacterium. Recent data also demonstrate that the
      exosporium of Bacillus cereus, a member of a genus of aerobic, Gram-positive,
      spore-forming rod-like bacilli, which includes the deadly Bacillus anthracis,
      contains a binding site for gC1qR. Therefore, by virtue of its ability to
      recognize plasma proteins such as C1q and HK, as well as bacterial and viral
      antigens, cell-surface gC1qR not only is able to generate proinflammatory
      byproducts from the complement and kinin/kallikrein systems, but also can be an
      efficient vehicle and platform for a plethora of pathogenic microorganisms.

PMID- 17544820
TI  - C1q binding and complement activation by prions and amyloids.
AB  - C1q binds to many non-self and altered-self-materials. These include
      microorganisms, immune complexes, apoptotic and necrotic cells and their
      breakdown products, and amyloids. C1q binding to amyloid fibrils found as
      extracellular deposits in tissues, and subsequent complement activation are
      involved in the pathology of several amyloid diseases, such as Alzheimer's
      disease. Prion diseases, such as scrapie also involve formation of amyloid by
      polymerization of the host prion protein (PrP). Complement activation is likely
      to contribute to neuronal damage in the end stages of prion diseases, but is also
      thought to participate in the initial infection, dissemination and replication
      stages. Infectious prion particles are likely to bind C1q and activate the
      complement system. Bound complement proteins may then influence the uptake and
      transport of prion particles by dendritic cells (DCs) and their subsequent
      proliferation at sites such as follicular DCs.

PMID- 17544821
TI  - The clearance of apoptotic cells by complement.
AB  - The complement system is implicated among others in the clearance of apoptotic
      cells, and deficiency for different components of the complement system is
      associated with aberrant handling of apoptotic material. As a result of this, it
      is thought that the complement system is involved in the pathogenesis of
      autoimmune diseases such as systemic lupus erythematosus (SLE) which affects
      multiple organs. In this review, the authors highlight the available data on
      complement and apoptosis, as well as the role of complement in severe autoimmune
      diseases like SLE.

PMID- 17544822
TI  - Role of ficolin in innate immunity and its molecular basis.
AB  - Ficolin is a multimeric protein consisting of an N-terminal collagen-like domain
      and a C-terminal fibrinogen-like domain. The structure is similar to mannose
      binding lectin (MBL) and complement C1q owing to the collagen-like stalk.
      Accumulating data indicate that a key function of ficolin is to recognize the
      carbohydrate moieties on pathogens as a pattern-recognition molecule. Two or
      three kinds of ficolin have been identified in each species of mammals. They are
      similar but with some differences in the expression site, location site, ligand
      binding specificity and ability to form complexes with MBL-associated serine
      proteases (MASPs). Like MBL, some ficolins are serum lectins and can form a
      complex with MASPs and small MBL-associated protein (sMAP). This complex
      activates the complement through "the lectin pathway". Our recent study suggests
      that ficolin acts through two distinct routes: the lectin pathway and a primitive
      opsonophagocytosis. All these observations suggest that ficolins function in
      clearance of non-self, based on their location sites and their molecular
      features.

PMID- 17544823
TI  - Surfactant protein A and surfactant protein D variation in pulmonary disease.
AB  - Surfactant proteins A (SP-A) and D (SP-D) have been implicated in pulmonary
      innate immunity. The proteins are host defense lectins, belonging to the
      collectin family which also includes mannan-binding lectin (MBL). SP-A and SP-D
      are pattern-recognition molecules with the lectin domains binding preferentially
      to sugars on a broad spectrum of pathogen surfaces and thereby facilitating
      immune functions including viral neutralization, clearance of bacteria, fungi and
      apoptotic and necrotic cells, modulation of allergic reactions, and resolution of
      inflammation. SP-A and SP-D can interact with receptor molecules present on
      immune cells leading to enhanced microbial clearance and modulation of
      inflammation. SP-A and SP-D also modulate the functions of cells of the adaptive
      immune system including dendritic cells and T cells. Studies on SP-A and SP-D
      polymorphisms and protein levels in bronchoalveolar lavage and blood have
      indicated associations with a multitude of pulmonary inflammatory diseases. In
      addition, accumulating evidence in mouse models of infection and inflammation
      indicates that recombinant forms of the surfactant proteins are biologically
      active in vivo and may have therapeutic potential in controlling pulmonary
      inflammatory disease. The presence of the surfactant collectins, especially SP-D,
      in non-pulmonary tissues, such as the gastrointestinal tract and genital organs,
      suggest additional actions located to other mucosal surfaces. The aim of this
      review is to summarize studies on genetic polymorphisms, structural variants, and
      serum levels of human SP-A and SP-D and their associations with human pulmonary
      disease.

PMID- 17544824
TI  - The immunoregulatory roles of lung surfactant collectins SP-A, and SP-D, in
      allergen-induced airway inflammation.
AB  - It has become increasingly evident that pulmonary surfactant proteins, SP-A and
      SP-D, present in the alveolar and bronchial epithelial fluid linings, not only
      play significant functions in the innate defense mechanism against pathogens, but
      also are involved in immunomodulatory roles, which result in the protection
      against, and resolution of, allergen-induced airway inflammation. Studies on
      allergen-sensitized murine models, and asthmatic patients, show that SP-A and SP
      D can: specifically bind to aero-allergens; inhibit mast cell degranulation and
      histamine release; and modulate the activation of alveolar macrophages and
      dendritic cells during the acute hypersensitive phase of allergic response. They
      also can alleviate chronic allergic inflammation by inhibiting T-lymphocyte
      proliferation as well as increasing phagocytosis of DNA fragments and clearance
      of apoptotic cell debris. Furthermore, it has emerged, from the studies on SP-D
      deficient mice, that, when these mice are challenged with allergen, they develop
      increased eosinophil infiltration, and abnormal activation of lymphocytes,
      leading to the production of Th2 cytokines. Intranasal administration of SP-D
      significantly attenuated the asthmatic-like symptoms seen in allergen-sensitized
      wild-type, and SP-D-deficient, mice. These important findings provide a new
      insight of the role that surfactant proteins play in handling environmental
      stimuli and in their immunoregulation of airway inflammatory disease.

PMID- 17544825
TI  - Association between cervicocephalic kinesthetic sensibility and frequency of
      subclinical neck pain.
AB  - Although impaired neck proprioception has been demonstrated in patients with
      chronic neck pain, previous studies have not consistently shown any association
      between pain intensity and proprioceptive performance. We therefore investigated
      whether temporal aspects of pain are associated with cervicocephalic kinesthetic
      sensibility. One hundred and twenty-seven adults with or without subclinical neck
      pain undertook two tasks, repositioning their heads to the neutral head position
      (head-to-NHP) and target position (head-to-target) in sagittal and transverse
      plane. Absolute error was calculated from position data recorded by an ultrasound
      based motion analysis system. Pain frequency, duration, and intensity were
      evaluated using a questionnaire. A mixed effects model was constructed to test
      the effect on reposition error by different pain factors, with age, gender and
      maximal cervical range of motion as covariates. A higher pain frequency was
      associated with greater reposition errors for all movement directions in the head
      to-NHP task. No consistent effect was observed for pain intensity or duration. In
      the case of the head-to-target task, no consistent effect was observed for any of
      the three pain factors. The findings reveal that pain frequency, not the
      intensity or duration of pain, is associated with neck proprioception in
      individuals with subclinical neck pain.

PMID- 17544826
TI  - Ultrasound imaging of the lateral abdominal wall muscles in individuals with
      lumbopelvic pain and signs of concurrent hypocapnia.
AB  - The purpose of this study was to compare the change in thickness of transversus
      abdominis (TrA) and internal oblique (IO) muscles, during resting supine
      respiration, in individuals with lumbopelvic pain (LP) to those who in addition
      to LP, demonstrate signs of concurrent hypocapnia (LP&HYPO). B-mode ultrasound
      images were obtained at the height of inspiration, and at the end of expiration,
      over three subsequent breaths during a single session. The average percent change
      in thickness of TrA during resting respiration in the LP&HYPO group (20.8+/-7.6%)
      was found to be statistically greater (P<0.001) than that of the LP only group
      (1.3+/-5.8%), while the difference between the groups for the percent change in
      thickness of IO (LP&HYPO 9.2+/-8.1%, LP 2.0+/-7.2%) did not differ (P=0.073).
      These findings suggest that respiratory modulation of TrA thickness, as measured
      by ultrasound imaging, greater than 20%, detected in a resting supine position,
      may be associated with an episode of hypocapnia, and if present warrants further
      investigation.

PMID- 17544828
TI  - Allergies, infections and the hygiene hypothesis--the epidemiological evidence.
AB  - The 'hygiene hypothesis' was first proposed by Strachan in 1989 suggesting that
      infections and unhygienic contact with older siblings or through other exposures
      may confer protection from the development of allergic illnesses. This hypothesis
      has evolved in various ways exploring the role of overt viral and bacterial
      infections, the significance of environmental exposure to microbial compounds,
      and their effect on underlying responses of innate and adaptive immunity. So far
      a truly unifying concept is still lacking, but various pieces of a complex
      interplay between a host's immune response, characteristics of the invading
      microorganism, the level and variety of the environmental exposure, and the
      interactions between a genetic background and a range of exposures become
      apparent. All these pieces eventually assemble to the clinical presentation of a
      complex syndrome namely of asthma and allergic illnesses. Even if today practical
      implications cannot directly be deduced from these findings, there is great
      potential for the development of novel preventive and therapeutic strategies in
      the future based on the concepts of the 'hygiene hypothesis'.

PMID- 17544829
TI  - Epidemiological and immunological evidence for the hygiene hypothesis.
AB  - Allergic diseases are inflammatory disorders that develop on the basis of complex
      gene-environment interactions. The prevalence of allergies is steadily increasing
      and seems to be associated with modern lifestyle. Therefore, it was hypothesized
      that high living standards and hygienic conditions are correlated with an
      increased risk for the development of an allergic disease. This so-called
      "hygiene hypothesis" states that due to reduced exposure to microbial components,
      the proposed allergy-preventing potential of these factors is no more present in
      sufficient qualities and/or quantities, which leads to an imbalance of the immune
      system with a predisposition to the development of allergic disorders. Meanwhile,
      several epidemiological studies were conducted supporting this concept and
      generating novel ideas for the underlying mechanisms that were then followed up
      by use of well-defined animal models and human studies. The current view of
      cellular and molecular mechanisms responsible for these phenomena includes
      changes in the fine balancing of T helper cell 1 (Th1), Th2 and regulatory T cell
      (Treg) responses which are triggered by altered or missing innate immune cell
      activation. In fact, proper activation of cells of the innate immune system via
      their so-called pattern recognition receptors has been demonstrated to play a
      crucial role in early shaping of the immune system and suppression of the
      development of Th2-driven allergic immune responses. These processes start
      already in utero and prenatal as well as early postnatal developmental stages
      seem to represent a certain "window of opportunity" for allergy-preventing
      environmental influences.

PMID- 17544830
TI  - Viral infections and allergies.
AB  - Respiratory viral infections have been implicated in the origin of, protection
      from and exacerbation of allergy-related symptoms in a variety of ways. Viral
      infections are closely linked to infantile wheezing. Severe bronchiolitis in
      early infancy may predispose to chronic childhood asthma as well as allergic
      sensitization; alternatively it could represent a marker of susceptible
      individuals. In contrast, repeated mild infections in early life may have a
      protective role in the development of asthma or atopy by driving the immune
      system towards Th1 responses. However, evidence on this hypothesis is not
      consistent as far as respiratory viruses are concerned. Several factors,
      including the presence of an atopic environment, timing of exposure and severity
      of the infection, interactively contribute to the allergy-infection relationship.
      In the present report, recent data on the role of viral infections in the
      development and progression of allergy and asthma are reviewed.

PMID- 17544831
TI  - Mycobacteria and allergies.
AB  - Exposure to mycobacteria was inevitable throughout mammalian evolution. Most
      mycobacteria are saprophytic environmental organisms that are enormously abundant
      in soil and untreated water and evoke immune responses in the residents of
      developing countries. A few species are pathogens. For example Mycobacterium
      tuberculosis, the causative agent of tuberculosis (TB), infects approximately 1/3
      of the world's population. Many individuals also receive vaccination with the
      Bacille Calmette Guerin (BCG), which is an attenuated form of the organism
      causing bovine TB. In order to understand the possible role that mycobacteria
      might have in the increases in allergic disorders over the last decades, it is
      necessary to dissect out these different mycobacterial influences. Above all it
      is essential, when analysing tuberculin test results, to distinguish between
      individuals who have latent TB and those who do not. Only then can probable
      effects of diverse types of exposure emerge. There is no doubt that in animal
      models mycobacteria can both prevent and treat allergic responses either by
      boosting Th1 or by driving allergen-specific regulatory T cells (RegT). Clinical
      trials in man remain inconclusive.

PMID- 17544832
TI  - Chronic helminth infections induce immunomodulation: consequences and mechanisms.
AB  - Worldwide, more than a billion people are infected with helminths. These worm
      infections generally do not lead to mortality, however, they are chronic in
      nature and can lead to considerable morbidity. Immunologically these infections
      are interesting; chronic helminth infections are characterized by skewing towards
      a T helper 2 type response as well as regulatory responses. The regulatory
      network is associated with chronic helminth infections and is thought to prevent
      strong immune responses against parasitic worms, allowing their long-term
      survival and restricting pathology. This regulatory network is thought to also
      temper responses to non-helminth antigens, like allergens or self-antigens,
      possibly leading to lower prevalence of allergies and autoimmune diseases in
      subjects that are chronically infected with helminths. This raises the
      interesting idea that helminths may bear molecules that have potential
      therapeutic action against allergies and possibly other inflammatory diseases.
      However, on the other side of the coin, this would predict that helminth infected
      subjects might not respond strongly to third party antigens like vaccines. This
      is an important issue, since most vaccines that are being developed against
      diseases such as HIV, tuberculosis or malaria will be introduced in areas where
      helminth infections are highly prevalent. Moreover, these vaccines are proving
      difficult to develop and are often weak, thus any confounder that would affect
      their efficacy needs to be taken into consideration. Helminth derived molecules
      have been identified that induce T helper 2 and regulatory responses via
      modulation of dendritic cells and some appear to do so via Toll like receptor
      (TLR) signaling. New insights into these pathways could be useful to antagonize
      suppression and hence boost vaccine efficacy or to optimize suppression induced
      by helminth derived molecules and control inflammatory diseases.

PMID- 17544833
TI  - Using house dust extracts to understand the immunostimulatory activities of
      living environments.
AB  - Laboratory and epidemiological studies have provided indirect but compelling
      evidence that toll-like receptor (TLR) signaling pathways play an important role
      in host responsiveness to ambient immunostimulatory factors. Nonetheless, direct
      evidence is limited. This paper will present our experience investigating the
      innate immunostimulatory activities of sterile house dust extracts (HDEs). In
      initial studies, bone marrow derived dendritic cells (BMDDCs) were cultured with
      HDEs, and cytokine production and co-stimulatory molecule expression were
      evaluated. In additional experiments, the TLR dependence of these responses was
      determined. HDEs induced concentration-dependent BMDDC activation. Moreover, the
      relative bioactivities of HDEs correlated with their endotoxin content. Finally,
      HDE-mediated responses were found to be partially dependent on TLR2, TLR4, and
      TLR9 and almost completely dependent on MyD88. These investigations provide the
      first direct evidence that TLR signaling pathways play a key role in innate
      responsiveness to non-infectious factors ubiquitous in living environments.

PMID- 17544834
TI  - The pro- and anti-inflammatory properties of human antigen-presenting cells
      expressing the high affinity receptor for IgE (Fc epsilon RI).
AB  - Almost 20 years after the first description of IgE on the surface of epidermal
      Langerhans cells (LC) and the subsequent characterization of the trimeric Fc
      epsilon RI on human antigen-presenting cells (APC), we have gained profound
      insights into the receptor responsible for this binding. Fc epsilon RI may act as
      a pro-inflammatory structure on some APC such as inflammatory dendritic epidermal
      cells (IDEC) in the skin of patients with atopic dermatitis while it can also be
      an important instrument in mechanisms leading to tolerance on other APC such as
      LC of the oral mucosa. By virtue of Fc epsilon RI, APC can initiate inflammation
      by secretion of a wide spectrum of pro-inflammatory cytokines and chemokines. Fc
      epsilon RI+DC can induce either Th2 or Th1 profile in T-cells. In contrast, the
      production of the tryptophan-catabolizing enzyme indoleamine 2,3-dioxygenase
      (IDO) as well as IL-10 and TGFss may contribute to the tolerogenic properties of
      DC.

PMID- 17544835
TI  - Mast cells in allergy: innate instructors of adaptive responses.
AB  - The function of mast cells as effector cells in allergy has been extensively
      studied. However, increasing insight into mast cell physiology has revealed new
      mast cell functions and has introduced mast cells as key players in the
      regulation of innate as well as adaptive immunity. For example, mast cells have
      recently been found to express Toll-like receptors (TLRs), which enable them to
      participate in the innate immune response against pathogens. Furthermore, mast
      cells have been reported to interact with B cells, dendritic cells and T cells
      and thereby modulate the direction of an adaptive immune response. Finally,
      recent documentation that mast cells express functional MHC class II and
      costimulatory molecules and release immunologically active exosomes, has raised
      the possibility that mast cells also engage in (as yet) poorly understood antigen
      presentation functions. In this review, we explore the hypothesis that mast cells
      serve as central mediators between innate and adaptive immunity, rather as pure
      effector cells, during allergic innate responses.

PMID- 17544836
TI  - Immunobiology of toll-like receptors in allergic disease.
AB  - Allergic diseases prevalence rates have increased dramatically over the last 50
      years in developed countries and one explanation might be that modern practices
      in public health lead to a decreased exposure towards pathogens resulting in a
      misguided immune response. Recently, it has become evident that immune responses
      against pathogens are initiated by Toll-like receptors (TLRs) that recognize a
      variety of structures derived from viruses, bacteria, fungi or protozoa. In this
      review we will discuss TLR ligands, TLR signaling in regard to Th1 and Th2 immune
      responses, their involvement in the development and their therapeutic potential
      in treatment of allergic disease.

PMID- 17544837
TI  - Requirement of N-glycosylation for the secretion of recombinant extracellular
      domain of human Fas in HeLa cells.
AB  - Apoptosis has been shown to be associated with altered glycosylation patterns and
      biosynthesis of glycoproteins. A major cell surface receptor involved in the
      induction of apoptosis is Fas that is activated by binding Fas ligand but can
      also be activated by binding anti-Fas antibody. In order to determine whether the
      Fas receptor is glycosylated, the extracellular domain of human Fas (shFas) was
      expressed as a cleavable fusion protein (shFas-Fc) in HeLa cells. These cells
      were shown to express activities of glycosyltransferases involved in N- and O
      glycan biosynthesis. The secreted shFas-Fc was shown to be a glycoprotein with
      heterogeneous glycan chains. MALDI mass spectrometry revealed a disperse
      molecular weight of shFas with an average of 23.4kDa. Western blots of shFas-Fc
      secreted from tunicamycin treated transfected HeLa cells showed that only N
      glycosylated glycoforms were secreted, while the unglycosylated shFas-Fc remained
      intracellular. The results suggest that both N-glycosylation sites of the
      extracellular domain of Fas are occupied with large N-glycans that play a role in
      the expression of the glycoprotein.

PMID- 17544838
TI  - Kinetics of uptake and deacetylation of N-acetylcysteine by human erythrocytes.
AB  - Overproduction of reactive oxygen species associated with several diseases
      including sickle cell anaemia reduces the concentration of glutathione, a
      principal cellular antioxidant. Glutathione depletion in sickle erythrocytes
      increases their conversion to irreversible sickle cells that promote vaso
      occlusion. Therapeutically, N-acetylcysteine partially restores glutathione
      concentrations but its mode of action is controversial. Following glutathione
      depletion, glutathione synthesis is limited by the supply of cysteine and it has
      been assumed that deacetylation of N-acetylcysteine within erythrocytes provides
      cysteine to accelerate glutathione production. To determine whether this is the
      case we studied the kinetics of transport and deacetylation of N-acetylcysteine.
      Uptake of N-acetylcysteine had a first order rate constant of 2.40+/-0.070min(-1)
      and only saturated above 10mM. Inhibition experiments showed that 56% of N
      acetylcysteine transport was via the anion exchange protein. Deacetylation,
      measured using (1)H NMR, had a K(m) of 1.49+/-0.16mM and V(max) of 2.61+/
      0.08micromolL(-1)min(-1). Oral doses of N-acetylcysteine increase glutathione
      concentrations in sickle erythrocytes at plasma N-acetylcysteine concentrations
      of approximately 10microM. At this concentration, calculated rates of N
      acetylcysteine uptake and deacetylation were approximately 5% of the rate
      required to maintain normal glutathione production. We concluded that on oral
      administration, intracellular deacetylation of N-acetylcysteine supplies little
      of the cysteine required for accelerated glutathione production. Instead, N
      acetylcysteine acts by freeing bound cysteine in the plasma that then enters the
      erythrocytes. To be effective, intracellular cysteine precursors must be designed
      to enter erythrocytes rapidly and employ enzymes with high activity within
      erythrocytes to liberate the cysteine.

PMID- 17544839
TI  - Clinically evaluated procedure for the reconstruction of vocal fold vibrations
      from endoscopic digital high-speed videos.
AB  - Investigation of voice disorders requires the examination of vocal fold
      vibrations. State of the art is the recording of endoscopic high-speed movies
      which capture vocal fold vibrations in real-time. It enables investigating the
      interrelation between disturbances of vocal fold vibrations and voice disorders.
      However, the lack of clinical studies and of a standardized procedure to
      reconstruct vocal fold vibrations from high-speed videos constrain the clinical
      acceptance of the high-speed technique. An image processing approach is presented
      that extracts the vibrating vocal fold edges from digital high-speed movies. The
      initial segmentation is principally based on a seeded region-growing algorithm.
      Even in movies with low image quality the algorithm segments successfully the
      glottal area by an introduced two-dimensional threshold matrix. Following
      segmentation, the vocal fold edges are reconstructed from the computed time
      varying glottal area. The performance of the procedure was objectively evaluated
      within a study comprising 372 high-speed recordings. The accuracy of vocal fold
      reconstruction exceeds manual segmentation results obtained by clinical experts.
      The algorithm reaches an information flow-rate of up to 98 images per second. The
      robustness and high accuracy of the procedure makes it suitable for the
      application in clinical routine. It enables an objective and highly accurate
      description of vocal fold vibrations which is essential to realize extensive
      clinical studies which focus on the classification of voice disorders.

PMID- 17544841
TI  - Tracking the social dimensions of RFID systems in hospitals.
AB  - BACKGROUND: Radio frequency identification (RFID) is an emerging technology that
      is rapidly becoming the standard for hospitals to track inventory, identify
      patients, and manage personnel. METHODS: Research involved qualitative methods
      including participant observation and interviews with hospital staff members and
      industry consultants in the United States. RESULTS: Hospital staff, especially
      nurses, expressed concern about the surveillance potential of these tracking
      technologies. Additionally, nursing staff frequently experience an
      intensification of labor as a result of the implementation of RFID systems
      because the task of keeping the systems operational often falls upon them.
      CONCLUSIONS: The social and organizational factors that contribute to the success
      or failure of RFID systems in hospitals must be further analyzed. The
      implications of RFID systems, such as privacy concerns and work intensification
      for nursing and other hospital staff, should be taken into account from the
      outset, especially during the design and implementation of the technology.

PMID- 17544840
TI  - The role of galectin-3 in cancer drug resistance.
AB  - The galectins comprise a family of 14 members of beta-galactoside-binding
      proteins, characterized by their affinity for beta-galactosides and by a
      conserved sequence in the carbohydrate recognition domain that bind to the
      carbohydrate portion of cell surface glycoproteins or glycolipids. Galectin-3, a
      31kDa gene product, is a multifunctional oncogenic protein which regulates cell
      growth, cell adhesion, cell proliferation, angiogenesis, and apoptosis. Recent
      studies have revealed that galectin-3 demonstrates anti-apoptotic effects which
      contribute to cell survival in several types of cancer cells. Intracellular
      galectin-3 in particular, which contains the NWGR anti-death motif of the Bcl-2
      family, inhibits cell apoptosis induced by chemotherapeutic agent such as
      cisplatin and etoposide in some types of cancer cells. We have also reported that
      nuclear export of phosphorylated galectin-3 regulates its anti-apoptotic activity
      in response to chemotherapeutic drugs. Here, we will describe the role of
      galectin-3 as an anti-apoptotic factor in response to chemotherapeutic drugs and
      will discuss recent data on its molecular mechanism that contribute to drug
      resistance. We suggest that targeting galectin-3 could improve the efficacy of
      anticancer drug chemotherapy in several types of cancer.

PMID- 17544842
TI  - Criterion-related validity and test-retest reliability of the 20m square shuttle
      test.
AB  - We assessed validity and reliability of the new 20m square shuttle run test (SST)
      for predicting maximal oxygen uptake (V O(2max)) and compared it with its
      predecessor, the 20m Multistage Shuttle Run Test (MST). In a repeated-measures
      randomised-block design, 74 healthy adult males performed the SST, the MST and a
      treadmill test (TT). To assess reliability, 40 of the total 74 volunteers were
      randomly-selected to perform the SST and MST twice. Unlike the SST (p>0.05), mean
      predicted V O(2max)(V predO(2max)) from the MST was significantly increased from
      that measured during the TT (p<0.05). The V predO(2max) from SST and MST
      correlated with TT V O(2max) at r=0.95 (p<0.001) and r=0.63 (p<0.001),
      respectively. Prediction error of SST was -0.3+/-3.3mlkg(-1)min(-1) with a
      coefficient of variation of +/-3.5%, while the equivalent values for MST were
      4.2+/-7.3mlkg(-1)min(-1) and +/-7.4%. Mean test-retest V predO(2max) did not
      differ for both SST and MST (p>0.05), while the corresponding test-retest
      correlation coefficients were r=0.85 (p<0.001) and r=0.72 (p<0.001). Reliability
      errors in 95% limits of agreement were 0.3+/-4.8 and 0.6+/-6.8mlkg(-1)min(-1)
      while coefficients of variation were +/-5.2% and +/-6.8% for the SST and MST,
      respectively. It is concluded that SST is a more valid proxy than MST for
      predicting laboratory V O(2max) based on the current procedures, while both tests
      are sufficiently reliable in healthy male adults.

PMID- 17544843
TI  - Making sporting clubs healthy and welcoming environments: a strategy to increase
      participation.
AB  - Sporting clubs are an ideal setting to promote community-wide participation in
      physical activity. Using the principles of the Ottawa Charter as a guide, this
      study explored the factors affecting the development of supportive environments
      as a mechanism to increase participation in club sport. The Victorian Health
      Promotion Foundation (VicHealth) funds State Sporting Associations (SSAs) to
      develop healthy and welcoming environments (HWE) in their associated clubs. The
      program focus areas are: welcoming and inclusive environments, sports injury
      prevention, 'smoke-free' environments, responsible serving of alcohol, sun
      protection and healthy eating. This paper sought to determine whether or not SSA
      Executive Officers (EOs) believe that the creation of a supportive environment
      will facilitate sporting club membership and to identify the factors that affect
      the development of the HWEs. Forty-two (82.4%) of the 51 funded SSAs completed a
      general survey and 36 (70.6%) of EOs responded to questions that were
      specifically addressed to them. EOs from six SSAs also participated in semi
      structured interviews. SSA EOs (97.2%) believed that the creation of HWE in clubs
      would facilitate increases in participant membership. However, the data indicate
      incomplete development of the HWE focus areas at the club level because of
      limited club capacity and limited SSA support. Reportedly, the SSAs are at the
      stage of raising program awareness at the club level. It is suggested that SSAs
      should plan a structured approach to the development of HWEs that acknowledges
      the diverse capacity of their clubs, and garner the support of key club
      volunteers in order to establish HWEs.

PMID- 17544844
TI  - Left atrial appendage aneurysm: a rare cause of paroxysmal supraventricular
      tachycardia.
AB  - Left atrial appendage aneurysm is a rare abnormality and a diagnostic dilemma in
      patients with cardiomegaly. Patients most commonly present with atrial
      tachyarrhythmias and thromboembolic events. Resection of the aneurysm is usually
      curative. We report herein the case of a 27-year-old man with massive left atrial
      appendage aneurysm diagnosed incidentally in the course of pre-operative
      evaluation for a non-cardiac surgery. The marked cardiomegaly detected in a
      routinely ordered pre-operative chest X-ray and the history of previous episodes
      of palpitation accompanied by chest discomfort guided us to the diagnosis. The
      diagnosis was made by transthoracic echocardiography and confirmed by angiography
      and then surgery.

PMID- 17544845
TI  - Bone-targeted radium-223 in symptomatic, hormone-refractory prostate cancer: a
      randomised, multicentre, placebo-controlled phase II study.
AB  - BACKGROUND: The alpha-emitter radium-223 ((223)Ra) is a bone-seeking radionuclide
      studied as a new treatment for patients with bone metastases from hormone
      refractory prostate cancer. We aimed to study mature outcomes from a randomised,
      multicentre, phase II study of (223)Ra. METHODS: Patients with hormone-refractory
      prostate cancer and bone pain needing external-beam radiotherapy were assigned to
      four intravenous injections of (223)Ra (50 kBq/kg, 33 patients) or placebo (31
      patients), given every 4 weeks. Primary endpoints were change in bone-alkaline
      phosphatase (ALP) concentration and time to skeletal-related events (SREs).
      Secondary endpoints included toxic effects, time to prostate-specific-antigen
      (PSA) progression, and overall survival. All tests were done at a 5% significance
      level, based on intention to treat. FINDINGS: Median relative change in bone-ALP
      during treatment was -65.6% (95% CI -69.5 to -57.7) and 9.3% (3.8-60.9) in the
      (223)Ra group and placebo groups, respectively (p<0.0001, Wilcoxon ranked-sums
      test). Hazard ratio for time to first SRE, adjusted for baseline covariates, was
      1.75 (0.96-3.19, p=0.065, Cox regression). Haematological toxic effects did not
      differ significantly between two groups. No patient discontinued (223)Ra because
      of treatment toxicity. Median time to PSA progression was 26 weeks (16-39) versus
      8 weeks (4-12; p=0.048) for (223)Ra versus placebo, respectively. Median overall
      survival was 65.3 weeks (48.7-infinity) for (223)Ra and 46.4 weeks (32.1-77.4)
      for placebo (p=0.066, log rank). The hazard ratio for overall survival, adjusted
      for baseline covariates was 2.12 (1.13-3.98, p=0.020, Cox regression).
      INTERPRETATION: (223)Ra was well tolerated with minimum myelotoxicity, and had a
      significant effect on bone-ALP concentrations. Larger clinical trials are
      warranted to study (223)Ra on the prevention of SREs and on overall survival in
      patients with hormone-refractory prostate cancer. Bone-targeting properties of
      (223)Ra could also potentially be used for treating skeletal metastasis from
      other primary cancers.

PMID- 17544846
TI  - The skin barrier, atopic dermatitis and allergy: a role for Langerhans cells?
AB  - The skin barrier (stratum corneum) is a major factor for determining the nature
      of immune response to antigens presented at the skin surface. Genetic
      abnormalities in skin barrier function are associated with allergy and atopic
      dermatitis, and removal of the skin barrier by tape stripping results in dominant
      Th2 responses to protein antigens. Langerhans cells take up antigen applied to
      skin from which the skin barrier has been removed; they then migrate to draining
      lymph nodes and initiate typical Th2 responses. These observations lead us to
      propose that the high frequency of allergic disease in the industrialized world
      might be due to lifestyle choices that result in loss of integrity of the skin
      barrier such as excessive washing and exfoliation of the skin.

PMID- 17544847
TI  - Excised V(D)J recombination byproducts threaten genomic integrity.
AB  - Signal joints were long considered to be inert byproducts of V(D)J recombination
      that protect the genome from illegitimate rearrangements. However, increasing
      evidence suggests that signal joints are not inert and could pose a threat to
      genomic stability. A recent study from Nadel and colleagues shows that episomal
      signal joints readily undergo trans recombination, resulting in their insertion
      into chromosomal DNA.

PMID- 17544848
TI  - Reprint of "efficacy of propentofylline, a glial modulating agent, on existing
      mechanical allodynia following peripheral nerve injury" [Brain Behav. Immun. 21
      (2007) 238-246].
AB  - Increasing evidence points to a role for spinal neuroimmune dysregulation (glial
      cell activation and cytokine expression) in the pathogenesis of chronic pain.
      Suppression of astrocytic and microglial activation with the methylxanthine
      derivative, propentofylline, pre-emptively attenuates the development of nerve
      injury-induced allodynia. Currently, we investigated the ability of systemic
      propentofylline to reverse existing, long-term allodynia after nerve injury-a
      clinically relevant paradigm. Rats received L5 spinal nerve transection or sham
      surgery and the development of mechanical allodynia was assessed daily for 2
      weeks, at which time injured rats exhibited robust responses to non-noxious von
      Frey filaments. On days 14-27, rats received either saline or 101 mg/kg
      propentofylline by intraperitoneal (i.p.) injection. On day 28 or 42 (after a 14
      day drug washout period), lumbar spinal cord sections were processed for
      assessment of astrocytic glial fibrillary acidic protein (GFAP) and microglial OX
      42 (antibody against CR3/CD11b). Propentofylline treatment to nerve injured rats
      resulted in significant reversal of allodynia that lasted throughout the 14-day
      washout period. Spinal microglial activation was observed at days 28 and 42 post
      injury at the protein level, in the absence of mRNA level changes. Less robust
      increases in GFAP immunoreactivity were observed at days 28 and 42 post
      transection. Interestingly, propentofylline treatment suppressed microglial
      activation at both time points in this paradigm. Taken together, our results
      highlight the clinical potential of the glial modulating agent, propentofylline,
      for the treatment of neuropathic pain as well as a role for microglia in the long
      term maintenance of allodynia.

PMID- 17544849
TI  - Molecular-functional imaging of cancer: to image and imagine.
AB  - The integration of advances in molecular biology, synthetic chemistry and
      visualization techniques has catapulted imaging into a molecular-functional
      realm, so that imaging is finding basic-research, preclinical and translational
      applications in cancer. Currently, molecular-imaging capabilities include the
      ability to image gene expression, receptors, signaling pathways, apoptosis,
      multidrug resistance and the extracellular matrix (ECM). Functional-imaging
      capabilities include the ability to assess angiogenesis, hypoxia and metabolism.
      Traditionally, imaging has played an important role in cancer diagnosing and
      determining response to treatment. However, it is the realization of the goal of
      noninvasively visualizing molecules and molecular pathways and relating these to
      function that makes multi-modality imaging such an exciting and powerful means
      for studying a multifaceted disease such as cancer.

PMID- 17544850
TI  - Epigenetic mechanisms of perinatal programming of hypothalamic-pituitary-adrenal
      function and health.
AB  - Environmental effects on the materno-foetal interaction determine birth outcomes
      that predict health over the lifespan. Thus, maternal undernutrition or stress
      associate with low birth weight, leading to an increased risk of metabolic and
      cardiovascular illness in the offspring. We argue that these effects are, in
      part, mediated by direct and indirect effects on the hypothalamic-pituitary
      adrenal (HPA) axis such that (i) the effect of maternal adversity on foetal
      growth is mediated by adrenal glucocorticoids and (ii) environmental adversity
      alters maternal physiology and behaviour, which then programs HPA activity in the
      offspring.

PMID- 17544851
TI  - The ecological relevance of transport in waste disposal systems in Western
      Europe.
AB  - With the development of modern waste management systems in Western Europe, a
      remarkable increase in the distances for waste transportation has been observed.
      The question thus arises whether recycling with longer transport distances is
      ecologically advantageous or whether disposal without recycling is to be
      preferred. This situation was analysed using selected product and waste streams.
      This included refrigerators, paper, polyethylene films and expanded polystyrene.
      For each of these streams, a life cycle analysis was conducted with an emphasis
      on waste transport. The system boundaries were set in terms of the generation of
      waste to recycling or landfilling. The comparison included several scenarios with
      recycling and different transport distances. Landfilling was used as the
      reference scenario. The results obtained demonstrated how transport distances
      influence the ecological benefit of recycling. In the case of expanded
      polystyrene, the ecological boundaries are reached in practical situations, while
      with other materials these boundaries are far from being attained. In these
      cases, more complex and elaborate collection schemes, such as kerbside
      collection, which is economically convenient and shows the highest collection
      rates, can also be recommended.

PMID- 17544852
TI  - Study of the effect of political measures on the citizen participation rate in
      recycling and on the environmental load reduction.
AB  - Obtaining the cooperation of citizens to participate in separate waste collection
      is essential to create a recycling-oriented society. In this research, the degree
      of change in the citizen participation rate, which occurs when the contents of
      political measures such as the raising of awareness, provision of information,
      and the conditions of collection services were changed, was estimated together
      with the effect on the reduction in environmental load. A questionnaire survey
      was conducted, targeted at residents of Itabashi Ward, while logistic regression
      analyses were also conducted to create predictive models for recycling behavior,
      and sensitivity analyses of the models were carried out to estimate the increase
      in citizen participation rate achievable through the implementation of various
      political measures. It was found that the effect of "thorough perception of
      information" was the largest, followed by "minimization of evaluation of trouble"
      and "thorough perception of efficacy of measures." The effect of the improvement
      in the citizen participation rate on the reduction in environmental load was also
      evaluated quantitatively by life cycle inventory analyses. It was indicated that
      "maximization of perception of information" had the greatest effect. However, the
      reduction effect with "paper packs" and "PET bottles" was relatively small
      compared with that of "bottles/cans."

PMID- 17544854
TI  - Fusion assessment of posterior lumbar interbody fusion using radiolucent cages: X
      ray films and helical computed tomography scans compared with surgical
      exploration of fusion.
AB  - BACKGROUND: Plain radiographic assessment of posterolateral fusion has been
      reported as accurate in only two thirds of patients who were found to be healed
      at surgical exploration. Plain radiographic techniques for fusion assessment of
      interbody fusion with radiolucent cages are reported to be accurate. A helical
      computed tomography (CT) scan shows a high sensitivity for pseudarthrosis
      compared with plain radiography. PURPOSE: To determine the accuracy of fusion
      assessment with plain X-ray films and helical CT scans by comparison to results
      of surgical exploration of fusion. STUDY DESIGN/SETTING: The accuracy and
      interobserver agreement of plain X-ray films and thin-cut helical CT scans were
      compared with fusion assessment by surgical exploration in patients with
      posterior lumbar interbody fusion using a radiolucent carbon fiber reinforced
      polymer cage (CFRP) and iliac crest bone graft. PATIENT SAMPLE: A review of 90
      patients who had surgical exploration of the lumbar fusion. OUTCOME MEASURES: All
      patients had plain X-ray films including Ferguson anteroposterior parallel to the
      interbody space. Fifty-four patients had thin-section helical CT scans. METHODS:
      Fusion assessment by exploration was compared with blinded assessment by plain X
      ray films and CT scans. RESULTS: Ninety patients had surgical exploration of 172
      lumbar interbody and posterolateral fusion levels. At the time of exploration,
      fusion was determined to be successful in 87 of 90 patients and 168 of 172 (97%)
      fusion levels. X-ray assessment showed healed interbody fusions in 87% and
      posterolateral fusion healed in 75%. CT grading of the interbody fusion found
      healed interbody fusion in 77%, and the posterolateral fusion was fused in 68%.
      Plain X-ray films and CT scans had a sensitivity of 100% for pseudarthrosis and a
      negative predictive value of 100% for healed fusion. Specificity was almost 90%
      and was not significantly different between X-ray films and CT scans.
      CONCLUSIONS: Fusion assessment with plain X-ray films and helical CT scans showed
      equal accuracy after posterior lumbar interbody fusion confirmed by surgical
      exploration. Our results indicate that when plain X-ray films show strong
      evidence of fusion or pseudarthrosis, the helical CT is unlikely to provide
      useful new information.

PMID- 17544855
TI  - Exposure to TBT increases accumulation of lipids and alters fatty acid
      homeostasis in the ramshorn snail Marisa cornuarietis.
AB  - Recent studies have shown that organotin compounds affect lipid homeostasis in
      vertebrates, probably through interaction with RXR and/or PPARgamma receptors.
      Molluscs are sensitive species to the toxic effects of tributyltin (TBT),
      particularly to masculinization, and TBT has been recently shown to bind to
      molluscs RXR. Thus, we hypothesized that exposure to TBT could affect lipid
      homeostasis in the ramshorn snail Marisa cornuarietis. For comparative purposes,
      the synthetic androgen methyl-testosterone (MT) was included in the study due to
      its masculinization effects, but its lack of binding to the RXR receptor. M.
      cornuarietis was exposed to different concentrations of TBT (30, 125, 500 ng/L as
      Sn) and MT (30, 300 ng/L) for 100 days. Females exposed to 500 ng/L TBT showed
      increased percentage of lipids and increased levels of fatty acids in the
      digestive gland/gonad complex (2- to 3-fold). In addition, fatty acid profiles
      were altered in both males and females exposed to 125 and 500 ng/L TBT. These
      effects were not observed in females exposed to MT. Overall, this work suggest
      that TBT acts as a potent inducer of lipid and fatty acid accumulation in M.
      cornuarietis as shown in vertebrate studies earlier, and that sex differences in
      sensitivity do exist.

PMID- 17544856
TI  - Restricting CAM consumption research: denying insights for practice and policy.

PMID- 17544857
TI  - A randomised comparative trial of yoga and relaxation to reduce stress and
      anxiety.
AB  - OBJECTIVE: To compare yoga and relaxation as treatment modalities at 10 and 16
      weeks from study baseline to determine if either of modality reduces subject
      stress, anxiety, blood pressure and improve quality of life. DESIGN: A randomised
      comparative trial was undertaken comparing yoga with relaxation. PARTICIPANTS:
      One hundred and thirty-one subjects with mild to moderate levels of stress were
      recruited from the community in South Australia. INTERVENTIONS: Ten weekly 1- h
      sessions of relaxation or hatha yoga. MAIN OUTCOME MEASURES: Changes in the State
      Trait Personality Inventory sub-scale anxiety, General Health Questionnaire and
      the Short Form-36. RESULTS: Following the 10 week intervention stress, anxiety
      and quality of life scores improved over time. Yoga was found to be as effective
      as relaxation in reducing stress, anxiety and improving health status on seven
      domains of the SF-36. Yoga was more effective than relaxation in improving mental
      health. At the end of the 6 week follow-up period there were no differences
      between groups in levels of stress, anxiety and on five domains of the SF-36.
      Vitality, social function and mental health scores on the SF-36 were higher in
      the relaxation group during the follow-up period. CONCLUSION: Yoga appears to
      provide a comparable improvement in stress, anxiety and health status compared to
      relaxation.

PMID- 17544858
TI  - Differences in perceived risks and benefits of herbal, over-the-counter
      conventional, and prescribed conventional, medicines, and the implications of
      this for the safe and effective use of herbal products.
AB  - OBJECTIVES: To investigate people's views about the efficacy and specific risks
      of herbal, over-the-counter (OTC) conventional, and prescribed conventional
      medicines, and their likelihood of taking a second (herbal or OTC conventional)
      product in addition to a prescribed medicine. METHODS: Experiment 1 (1 factor
      within-participant design); Experiment 2 (1 factor between-participant design).
      Convenience samples of general population were given a hypothetical scenario and
      required to make a number of judgements. RESULTS: People believed herbal remedies
      to be less effective, but less risky than OTC and prescribed conventional
      medicines. Herbal medicines were not seen as being safer simply because of their
      easier availability. Participants indicated that they would be more likely to
      take a herbal medicine than a conventional OTC medicine in addition to a
      prescribed medicine, and less likely to consult their doctor in advance.
      CONCLUSION: People believe that herbal medicines are natural and relatively safe
      and can be used with less caution. People need to be given clear information
      about the risks and benefits of herbal medicines if they are to use such products
      safely and effectively.

PMID- 17544859
TI  - Acupuncture as a complex intervention for depression: a consensus method to
      develop a standardised treatment protocol for a randomised controlled trial.
AB  - OBJECTIVE: To standardise a complex intervention by defining the characteristic
      (specific) components of treatment for a randomised controlled trial of
      acupuncture as an intervention for individuals who have been diagnosed with
      depression using a consensus method. METHODS: A nominal group technique was used.
      Potential components of the acupuncture intervention were generated from the
      literature, experts and participants. These were categorised as constant or
      variable, the latter including active management techniques (such as providing
      relevant explanations), auxiliary techniques (such as auricular acupuncture), and
      other aspects of patient care (such as offering life-style and dietary advice),
      all of which were underpinned by defined theoretical frameworks. Participants
      were selected on the basis of their experience and training, to encompass a
      diverse range of styles of traditional acupuncture practice in the UK, and all
      rated components in two rounds. RESULTS: Fifteen practitioners rated 52 variable
      components in the first round and 55 in the second. There was group support for
      16 active management components, three auxiliary techniques and five areas of
      life-style support, all driven by eight theoretical diagnostic and treatment
      frameworks. For the 39 components that were rated twice, group support increased
      between rounds from 75 to 79% (z=-2.2, p=0.03), while the absolute average
      deviation from the median dropped from 1.04 to 0.83 (z=-2.5, p=0.011).
      CONCLUSION: Standardising the characteristic components of a complex intervention
      for a randomised controlled trial of acupuncture for depression using a consensus
      approach is feasible. The method can be generalised to other clinical situations
      and other treatment modalities.

PMID- 17544860
TI  - Exploring acupuncturists' perceptions of treating patients with rheumatoid
      arthritis.
AB  - AIMS: To outline acupuncturists' perceptions of treating patients with rheumatoid
      arthritis (RA), exploring the impact of practitioner affiliation to a traditional
      or western theoretical base. METHODS: Qualitative study utilising Grounded Theory
      Method. Nineteen acupuncturists were chosen via theoretical sampling. In-depth
      semi-structured interviews were tape-recorded and transcribed. Field notes were
      also taken. Emerging categories and themes were identified. RESULTS: Inter
      affiliatory differences were identified in the treatments administered and the
      scope and emphasis of intended therapeutic effects. Limited divergence was found
      between acupuncturists' perceptions of treatment outcomes. Factors perceived as
      impacting on treatment outcomes were identified. CONCLUSIONS: Clinical trials of
      acupuncture in RA may have failed to administer a treatment which reflects that
      administered in clinical practice. Outcome measures employed in clinical trials
      of acupuncture in RA, as well as established outcome indices for RA, may lack the
      necessary breadth to accurately assess acupuncture's efficacy. Acupuncturist
      affiliation has demonstrable implications for the practice and research of
      acupuncture.

PMID- 17544861
TI  - Effect of Acu-TENS on recovery heart rate after treadmill running exercise in
      subjects with normal health.
AB  - OBJECTIVE: This study aims to investigate the effect of transcutaneous electrical
      nerve stimulation, applied at bilateral acupuncture points PC6 (Acu-TENS), on
      recovery heart rate (HR) in healthy subjects after treadmill running exercise.
      DESIGN: A single blinded, randomized controlled trial. SETTING: Laboratory with
      healthy male subjects (n=28). INTERVENTIONS: Each subject participated in three
      separate protocols in random order. PROTOCOL A: The subject followed the Bruce
      protocol and ran on a treadmill until their HR reached 70% of their maximum (220
      age). At this 'target' HR, the subject adopted the supine position and Acu-TENS
      to bilateral PC6 was commenced. PROTOCOL B: Identical to protocol A except that
      Acu-TENS was applied in the supine position for 45min prior to, but not after
      exercise. PROTOCOL C: Identical to protocol A except that placebo Acu-TENS was
      applied. MAIN OUTCOME MEASURES: Heart rate was recorded before and at 30s
      intervals after exercise until it returned to the pre-exercise baseline. The time
      for HR to return to baseline was compared for each protocol. RESULTS: Acu-TENS
      applied to bilateral PC6 resulted in a faster return to pre-exercise HR compared
      to placebo. Time required for HR to return to pre-exercise level in protocols A-C
      was 5.5+/-3.0; 4.8+/-3.3; 9.4+/-3.7 min, respectively (p<0.001). There was no
      statistical difference in HR recovery time between protocols A and B. Subjects
      expressed the lowest rate of perceived exertion score (RPE) at 70% maximum HR
      with protocol B. CONCLUSION: This study suggests that Acu-TENS applied to PC6 may
      facilitate HR recovery after high intensity treadmill exercise.

PMID- 17544862
TI  - Effect of homeopathic treatment of 60 Japanese patients with chronic skin
      disease.
AB  - BACKGROUND: Many individuals who appear to suffer from incurable chronic skin
      disease use complementary and alternative medicine (CAM). Homeopathy has recently
      increased in popularity among patients with skin disease. The effects of
      homeopathic treatment have yet to be fully investigated in patients for whom
      conventional dermatological treatment is not sufficiently effective. OBJECTIVES:
      To describe patient-reported and clinically observed effects of individualized
      homeopathic treatment of chronic skin disease. PATIENTS AND METHODS: The
      effectiveness of individualized homeopathic treatment was measured using the
      patients' own assessments of seven elements (overall impression, improvement of
      skin condition, reduction of itchiness, reduction of sleep disturbance,
      satisfaction in daily life, fulfillment at work and satisfaction in human
      relations) using a nine-point scale similar to the Glasgow Homeopathic Hospital
      Outcome Scale (GHHOS). Sixty patients with chronic skin disease were included in
      the study: atopic dermatitis (AD) (n=25), eczema other than AD (n=20), severe
      acne (n=6), chronic urticaria (n=6), psoriasis vulgaris (n=2) and alopecia
      universalis (n=1). These patients received individualized homeopathic treatments
      in addition to conventional dermatological treatments for a period of from 3
      months to 2 years 7 months. RESULTS: Six patients reported a score of 4 (complete
      recovery), 23 patients a score of 3 (75% improvement), 24 patients a score of 2
      (50% improvement) and 7 patients a score of 1 (25% improvement). A total of 88.3%
      of patients reported over 50% improvement. Around one-half the patients with AD
      and eczema reported greater satisfaction in daily life, greater fulfillment at
      work and greater satisfaction in human relations. CONCLUSIONS: The psychological,
      physical and psychosomatic symptoms and effects of chronic skin diseases are
      inextricable. Individualized homeopathic treatment can provoke a good response in
      patients with chronic skin disease; therefore, the holistic approach used in
      homeopathy may be a useful strategy alongside conventional treatment.

PMID- 17544863
TI  - Should your GP be an osteopath? Patients' views of an osteopathy clinic based in
      primary care.
AB  - BACKGROUND: Spinal pain is a common reason for consulting general practitioners
      (GPs), and complementary therapists such as osteopaths and chiropractors.
      Patients express greater satisfaction with the care from chiropractors and
      osteopaths, because they are perceived as having more empathy, diagnostic skill
      and effective treatment, but their attitude to a GP providing an osteopathy
      service is unknown. AIM: To explore patients' views of receiving osteopathy in
      contrast with usual GP care, to provide insight into the psychological benefit of
      treatment, and to explore their views on how such a service should be provided
      and funded. DESIGN OF STUDY: Qualitative study using semi-structured interviews
      preceded by short questionnaires. SETTING: Primary care osteopathy clinic
      treating patients from Llanfairfechan Health Centre, which also accepted
      referrals from neighbouring practices in North West Wales in a randomised
      controlled trial. METHOD: Short questionnaires followed by semi-structured
      interviews with 20 participants. The interview transcripts were analysed by open
      coding into categories, axial coding to define the categories' properties and
      selective coding for the final thematic account. RESULTS: Traditional GP skills
      were valued, but GP care for spinal pain was perceived as limited and
      ineffective. Osteopathy was attractive because it did not involve drugs, but it
      had short-term painful side effects, and some found it frightening. Physical
      benefits included increased mobility and reduced pain; psychological benefits
      included removal of fear and improved understanding. Provision of osteopathy by a
      GP was welcomed, so long as the GP was properly qualified, and had sufficient
      time. CONCLUSION: A GP run osteopathy clinic provided additional physical and
      psychological benefit. GP consultation might be improved by adopting some
      features from the osteopathic consultation.

PMID- 17544864
TI  - The in vitro evidence for an effect of high homeopathic potencies--a systematic
      review of the literature.
AB  - OBJECTIVE: Systematic assessment of the in vitro research on high potency
      effects. METHOD: Publications of experiments were collected through databases,
      experts, previous reviews, citation tracking. INCLUSION CRITERIA: stepwise
      agitated dilutions <10(-23); cells or molecules from human or animal. Experiments
      were assessed with the modified SAPEH score. RESULTS: From 75 publications, 67
      experiments (1/3 of them replications) were evaluated. Nearly 3/4 of them found a
      high potency effect, and 2/3 of those 18 that scored 6 points or more and
      controlled contamination. Nearly 3/4 of all replications were positive. Design
      and experimental models of the reviewed experiments were inhomogenous, most were
      performed on basophiles. CONCLUSIONS: Even experiments with a high methodological
      standard could demonstrate an effect of high potencies. No positive result was
      stable enough to be reproduced by all investigators. A general adoption of
      succussed controls, randomization and blinding would strengthen the evidence of
      future experiments.

PMID- 17544865
TI  - The in vitro evidence for an effect of high homeopathic potencies--a systematic
      review of the literature.

PMID- 17544866
TI  - General practitioners and St. John's Wort: a question of regulation or knowledge?
AB  - BACKGROUND: St. John's Wort (SJW), also known as Hypericum perforatum, is a
      herbal remedy available over-the-counter. There is evidence that it can treat
      mild to moderate depression but has potential side effects and important drug
      interactions. OBJECTIVE: To determine general practitioners' (GPs') knowledge and
      recommendation of SJW for mild to moderate depression within a climate of
      widespread community use of complementary therapies and debate about regulation.
      DESIGN AND SETTING: Postal survey of a random sample of 350 Australian GPs.
      RESULTS: Forty-eight percent responded. One-third (31%) reported recommending SJW
      to patients with mild to moderate depression. Of these, only one-third (32%)
      reported specific dosage instructions. Respondents' knowledge of side effects and
      interactions was much less than for selective serotonin reuptake inhibitor
      antidepressants. CONCLUSIONS: Australian GPs know less about safety of SJW than
      antidepressants and do not widely recommend it to patients. Despite this, many
      patients use SJW, probably in combination with other pharmaceuticals. Effective
      dissemination of further research into effectiveness and risk profiles of
      complementary therapies is needed to inform health professionals, regulatory
      bodies and consumers.

PMID- 17544867
TI  - Mind/body medicine: a report on a sub-topic of the North American Research
      Conference on Complementary and Integrative Medicine on 24-27 May 2006 in
      Edmonton, Canada.

PMID- 17544868
TI  - Guilt-by-association feature selection: identifying biomarkers from proteomic
      profiles.
AB  - In recent years, proteomic profiling by mass spectrometry has opened up a new
      realm of methods for identifying potential biomarkers. Mass spectrometry data,
      like other proteomic and genomic data, are challenging to analyze because of
      their high dimensionality and the availability of few samples. Hence, feature
      selection is extremely important because it directly provides a list of potential
      biomarkers by choosing a subset of effective features that separate diseased
      samples from healthy ones. The rule of thumb for feature selection is that
      features must be discriminant and independent for the best separation of the two
      groups. However, in general, existing feature selection algorithms only take into
      account the discrimination ability of features. In this paper, we present a novel
      method for feature selection, guilt-by-association feature selection (GBA-FS).
      The algorithm makes it possible to select features that are independent as well
      as discriminant. After measuring similarities between features, the algorithm
      groups together similar features using a clustering algorithm, and selects the
      best representative feature from each group. As a result, it produces a list of
      discriminant and independent features. The efficacy of GBA-FS was extensively
      tested on two real-world SELDI TOF data sets. The experimental results
      demonstrate that GBA-FS assists in selecting more independent features as
      compared to a common filter type feature selection method, the t test. The
      results also show that GBA-FS can be used to deconvolve multiply charged states
      of the same protein molecules. As GBA-FS successfully identifies feature groups
      with similar mass values, it can also be employed as an alternative to peak
      detection for preprocessing the mass spectrometry data.

PMID- 17544869
TI  - Recurrent left-sided colon volvulus leading to mediastinal shift.

PMID- 17544870
TI  - Alteration of gastric functions and candidate genes associated with weight
      reduction in response to sibutramine.
AB  - BACKGROUND & AIMS: It is unclear whether weight loss with the noradrenergic
      (norepinephrine) and serotonergic (5-hydroxytryptamine) reuptake inhibitor,
      sibutramine, is associated with altered stomach functions and whether genetics
      influence treatment response. METHODS: Forty-eight overweight and obese but
      otherwise healthy participants were randomized to placebo or sibutramine (15
      mg/day for 12 weeks). At baseline and posttreatment we measured the following:
      gastric emptying for solids and liquids by scintigraphy, gastric volumes by
      single-photon emission computed tomography, maximum tolerated volume and 30
      minute postnutrient challenge symptoms, and selected gastrointestinal hormones.
      All participants received structured behavior therapy for weight management. The
      influence of candidate gene polymorphisms involved in norepinephrine and 5
      hydroxytryptamine or receptor function (phenylethanolamine N-methyltransferase,
      guanine nucleotide binding protein beta polypeptide 3, alpha2A adrenoreceptor,
      and solute carrier family 6 [neurotransmitter transporter, serotonin] member 4
      [homo sapiens] [SLC6A4]) on weight loss and gastric functions was evaluated.
      RESULTS: The overall average weight loss posttreatment was 5.4 +/- 0.8 (SEM) kg
      with sibutramine and 0.9 +/- 0.9 kg with placebo (P < .001). The sibutramine
      group showed significant retardation in gastric emptying of solids (P = .03),
      reduced maximum tolerated volume (P = .03), and increased postprandial peptide YY
      compared with the placebo group. Obese females showed greater effects of
      sibutramine on weight loss and gastric emptying of solids and liquids. Gastric
      volumes and postchallenge symptoms were not significantly different in the 2
      treatment groups. The LS/SS genotype of the promoter for SLC6A4 was associated
      with enhanced weight loss with sibutramine. CONCLUSIONS: Weight reduction with
      sibutramine is associated with altered gastric functions and increased peptide YY
      and is significantly associated with SLC6A4 genotype. The role of genetic
      variation in SLC6A4 on weight loss in response to sibutramine deserves further
      study.

PMID- 17544871
TI  - A prospective multivariate analysis of clinical factors associated with pouchitis
      after ileal pouch-anal anastomosis.
AB  - BACKGROUND & AIMS: Although acute pouchitis (AP) after ileal pouch-anal
      anastomosis (IPAA) for UC is common and easily treated, chronic pouchitis (CP)
      remains a difficult management issue. The aim of this study was to identify
      important clinical risk factors associated with AP or CP. METHODS: AP and CP were
      prospectively assessed, and demographic, disease, and treatment characteristics
      were tabulated. Univariate and multivariate analyses were performed to evaluate
      associations between AP or CP and potential risk factors. RESULTS: Two hundred
      IPAA patients were followed for a median of 24 months (range, 3-117 months).
      Thirty-six patients (18%) developed AP, and 23 patients (12%) developed CP. On
      univariate analysis, the use of steroids before colectomy and smoking were
      associated with the development of AP. CP was associated with male gender,
      smoking, length of follow-up, extraintestinal manifestations, backwash ileitis,
      and elevated (450x10(9)/L) platelet count. On multivariate analysis, the
      following risk factors were found to be independently associated with AP: use of
      steroids before colectomy (odds ratio [OR], 3.7; 95% confidence interval [CI],
      1.5-8.9; P = .004) and smoking (OR, 2.3; 95% CI, 1.1-5.3; P = .04). CP was
      directly associated with extraintestinal manifestations (OR, 3.5; 95% CI, 1.1
      11.1; P = .03), elevated platelet count (OR, 3.1; 95% CI, 1.1-8.9; P = .03), and
      increased length of follow-up (OR, 1.3; 95% CI, 1.1-1.6; P = .002). Smoking
      reduced the incidence of CP (OR, 0.2; 95% CI, 0.05-0.74; P = .04). CONCLUSIONS:
      Clinical factors associated with AP included use of steroids before colectomy and
      smoking. Factors directly related to CP were extraintestinal manifestations,
      elevated platelet count, and length of follow-up after IPAA. Smoking appears to
      protect against the development of CP.

PMID- 17544872
TI  - Novel zoom endoscopy technique for diagnosis of small flat gastric cancer: a
      prospective, blind study.
AB  - BACKGROUND & AIMS: During gastroscopy we frequently encounter flat reddened
      lesions in the stomach. Making a correct diagnosis of flat small early gastric
      cancer is dependent not on endoscopic diagnosis, but on histopathologic diagnosis
      of biopsy specimens alone. We investigated the diagnostic accuracy of magnified
      endoscopic findings for differentiating between reddened mucosa caused by
      gastritis and flat reddened gastric cancer, prospectively and blindly. METHODS: A
      total of 603 consecutive patients were examined by upper-gastrointestinal zoom
      endoscopy and the prevalence of each of the following magnified endoscopic
      findings, which already had been reported as characteristic for differentiated
      carcinoma, was recorded: (1) presence of a demarcation line between the reddened
      lesion and the surrounding mucosa, (2) disappearance of the regular subepithelial
      capillary network pattern, and (3) presence of an irregular microvascular pattern
      within the flat reddened lesion. Patients with known gastric carcinomas were
      excluded from this study. RESULTS: A total of 158 flat reddened lesions from 158
      patients were detected. Pathologically, 144 flat reddened lesions showed only
      gastritis, whereas 14 lesions were newly diagnosed as carcinoma. Regarding
      diagnostic accuracy for carcinoma, the negative predictive values of the presence
      of a demarcation line and disappearance of the regular subepithelial capillary
      network pattern were 100% and 100%, respectively, and the diagnostic accuracy of
      the irregular microvascular pattern was 98.7%. CONCLUSIONS: The novel zoom
      endoscopic findings based on microvascular architecture are very useful for
      making a differential diagnosis between flat early gastric carcinoma and
      gastritis.

PMID- 17544873
TI  - Colonoscopy technique in consecutive patients referred for prior incomplete
      colonoscopy.
AB  - BACKGROUND & AIMS: Cecal intubation is one of the goals of colonoscopy. In some
      patients cecal intubation is unsuccessful. The aim of this study was to describe
      the approach used by a gastroenterologist with special interest in colonoscopy to
      perform colonoscopy in patients with a prior incomplete colonoscopy. METHODS: The
      demographic features and colonoscopy methods and findings are described in 119
      consecutive patients in whom a prior incomplete colonoscopy was performed by a
      gastroenterologist or surgeon. RESULTS: Most patients could be characterized as
      to the cause of previous failure, based on medical records or an initial attempt
      to pass the colonoscope, as redundant colon (n = 54), difficult sigmoid colon (n
      = 33), or difficult to sedate (n = 8). Colonoscopy was successful to the cecum (n
      = 116) or an ileocolonic anastomosis (n = 1) in 117 of the 119 patients. Standard
      adult (n = 51) and pediatric colonoscopes (n = 35) and attention to careful
      technique were successful in 86 cases, although these included 7 cases in which
      the use of propofol sedation appeared to be the critical factor allowing success.
      Special equipment was needed in 31 cases: external straighteners (n = 9), upper
      endoscopes alone (n = 9), pediatric colonoscope after guidewire exchange (n = 8),
      and an enteroscope with (n = 4) or without (n = 1) an external straightener.
      CONCLUSIONS: Most patients with a prior incomplete colonoscopy can be
      colonoscoped successfully if an array of tools and techniques are used. The
      approach varies depending on characterization of the problem as redundant colon
      vs difficult sigmoid colon. The approach and techniques described here may be of
      value to others in cases of a difficult or challenging colonoscopy.

PMID- 17544874
TI  - Nonsurgical management of asymptomatic incidental pancreatic cysts.
AB  - BACKGROUND & AIMS: Cystic lesions of the pancreas are detected more often
      nowadays. Many are considered premalignant and pancreatic resection is
      recommended. This study was undertaken to assess the natural course of
      asymptomatic pancreatic cysts and their malignant potential. METHODS: All
      patients referred for endoscopic ultrasound (EUS) between 1994 and 2003 because
      of pancreatic cystic lesions were included. RESULTS: A total of 135 patients
      underwent EUS because of pancreatic cysts. Twenty-three patients were excluded
      because they were symptomatic or had pancreatic pseudocysts. The other 112
      patients were diagnosed as having true pancreatic cysts. Fourteen of the 112
      patients were referred for surgery based on either unfavorable EUS morphology or
      fine-needle aspiration results. In 4 (29%) of 14 surgical specimens, the
      histology was that of malignancy. An additional 8 patients with serous
      cystadenoma and pseudocysts were excluded from the analysis. The remaining 90
      patients were defined as having indeterminate or mucinous cysts and were managed
      conservatively. The follow-up period lasted between 12 and 180 months (mean, 48
      +/- 33 mo). Malignancy was diagnosed in only 1 patient after 7 years of follow-up
      evaluation. None of the 57 patients available for clinical follow-up evaluation
      became symptomatic. The size of the cyst remained unchanged in 45 patients,
      increased in 2, and resolved in 9. Thirty-three patients were followed up through
      the Israel Registry: 31 were alive and 2 died from unrelated causes. CONCLUSIONS:
      Our data suggest that a considerable number of asymptomatic pancreatic cystic
      lesions can be managed conservatively, at least for a mean period of 4 years.
      Malignant transformation in pancreatic cystic lesions probably is less frequent
      than previously reported.

PMID- 17544875
TI  - Immune response to influenza vaccine in pediatric patients with inflammatory
      bowel disease.
AB  - BACKGROUND & AIMS: The aim of this study was to compare response to inactivated
      influenza vaccine in healthy children and pediatric patients with inflammatory
      bowel disease (IBD). METHODS: A prospective, open-label, controlled clinical
      trial during influenza seasons of 2002-2004 was performed. Single-dose inactive
      trivalent influenza vaccine was administered. Immune response to vaccination was
      measured by pre-immunization and postimmunization hemagglutinin inhibition
      titers. A postimmunization hemagglutinin inhibition titer of 40 or higher was
      considered protective against influenza. IBD activity and adverse events were
      recorded. RESULTS: Eighty subjects were enrolled (29 healthy controls, 51 IBD
      patients). One patient did not complete the study. Patients were divided into 3
      subgroups: infliximab and immunomodulatory (16), immunomodulatory (20), and anti
      inflammatory therapy (14). Immunomodulatory therapy included corticosteroids, 6
      mercaptopurine, or methotrexate. Overall, there was a statistically significant
      decrease in immune response in patients compared with healthy controls who
      received 1 influenza vaccine antigen (B/Hong Kong, P = .0125). Patients receiving
      infliximab and immunomodulatory therapy were less likely to respond to 2
      influenza vaccine antigens (A/New Caledonia/20/99 and B/Hong Kong/330/2001, P =
      .018 and .0002, respectively). Fifteen subjects (19%) reported 19 mild adverse
      events: 11 (14%) reported soreness at the site, 4 (5%) reported having a cold, 3
      (4%) reported flu-like symptoms, and 1 (1%) reported a headache. The clinical
      activity of IBD was not affected by vaccination. CONCLUSIONS: The serologic
      conversion rate to influenza vaccine in patients with IBD ranged from 33% to 85%.
      Patients on concomitant infliximab and immunomodulatory therapy are at risk of
      inadequate response to vaccination. The vaccine was safe and did not affect IBD
      activity.

PMID- 17544876
TI  - Improvement of staging by combining tumor and treatment parameters: the value for
      prognostication in rectal cancer.
AB  - BACKGROUND & AIMS: Staging of cancer is based on the TNM system. This valuable
      system takes only tumor-related parameters into account, but in the era of
      refined surgery and preoperative therapy treatment-related factors are of equal
      importance. By using rectal cancer as a model we explored the hypothesis that a
      combination of tumor- and treatment-related parameters will result in improved
      prognostication. METHODS: Standardized clinicopathologic and histologic factors
      considered predictive for survival were studied in eligible patients treated in a
      trial for rectal cancer (n = 1324). These factors were analyzed in relation to
      survival using log-rank tests, Kaplan-Meier curves, and Cox regression both
      individually and in combination, the latter including TNM staging. A second data
      set from an independent trial (n = 316) was used for data validation. RESULTS:
      Multivariate analysis identified nodal status (P = .001) and circumferential
      margin (P = .001) involvement as the most important prognostic factors for
      survival. The combination of these factors formed an improved staging system
      (node status and circumferential margin [NCRM]) compared with the present TNM
      staging with respect to 5-year cancer-specific survival. The results were
      confirmed in our independent patient population. CONCLUSIONS: NCRM staging of
      rectal cancer results in a broad range of survival rates and favorable patient
      grouping. Our data give strong evidence that a staging system combing tumor- and
      treatment-related factors provides better prognostic information than the classic
      TNM system, which is based solely on tumor-related factors. Similar results might
      be obtained in other types of cancer in which quality of treatment is important
      for outcome.

PMID- 17544877
TI  - Comparison of the interobserver reproducibility with different histologic
      criteria used in celiac disease.
AB  - BACKGROUND & AIMS: The Marsh-Oberhuber classification of duodenojejunal mucosal
      lesions is currently used for celiac disease. A more simplified classification,
      which is based on 3 villous morphologies (A, non-atrophic; B1, atrophic, villous
      crypt ratio <3:1; B2, atrophic, villi no longer detectable) and an
      intraepithelial lymphocyte count of >25/100 enterocytes, has recently been
      proposed. The aim of the study was to asses the interobserver agreement between
      different pathologists in classifying celiac disease lesions according to both
      Marsh-Oberhuber and the new classification system. METHODS: Sixty patients were
      selected for the study: 10 subjects without celiac disease, 13 celiac patients
      with normal villi but a pathologic increase in intraepithelial lymphocytes
      >25/100 and hyperplastic crypts, and 37 patients with celiac disease with villous
      atrophy. Sixty slides were sent to 6 pathologists, who were blinded to each other
      and were not given any clinical information. Each pathologist received the set of
      biopsy specimens on 2 separate occasions and had to evaluate them according to
      both grading systems in a random order. The kappa statistic was used to assess
      agreement between each pair of pathologists. RESULTS: Overall, mean kappa values
      were 0.35 (fair) for the Marsh-Oberhuber classification versus 0.55 (moderate)
      for the new classification system. CONCLUSIONS: The new classification for
      duodenal pathology in celiac disease gives better interobserver agreement
      compared with the more cumbersome Marsh-Oberhuber classification and contributes
      to the validity of diagnosis in celiac disease.

PMID- 17544878
TI  - Effect of sustained viral response on hepatic venous pressure gradient in
      hepatitis C-related cirrhosis.
AB  - BACKGROUND & AIMS: Interferon-based therapy can improve hepatic histology in
      chronic hepatitis C (CHC)-related cirrhosis but its effect on portal hypertension
      is unclear. The aims of this study were to investigate the effect of treatment
      with peginterferon alfa-2a and ribavirin on hepatic venous pressure gradient
      (HVPG) in CHC with compensated cirrhosis. METHODS: Forty-seven patients with
      compensated biopsy examination-proven cirrhosis were recruited from 2
      metropolitan teaching hospitals and were treated for 48 weeks with combination
      peginterferon alfa-2a 180 microg by subcutaneous injection weekly and ribavirin
      800-1200 mg/day orally. A transjugular liver biopsy examination and HVPG
      measurement were performed at baseline, and 33 patients had a repeat HVPG
      measurement after 6 months of treatment-free follow-up evaluation. RESULTS: The
      overall sustained viral response (SVR) was 21%. Posttreatment there was a
      significant decrease in HVPG level in sustained responders compared with
      nonresponders (-2.1 +/- 4.8 vs 0.6 +/- 2.8 mm Hg; P = .05). Among patients with
      portal hypertension, a higher proportion of sustained responders achieved a 20%
      or greater reduction in HVPG level compared with nonresponders (71% vs 20%; P =
      .01). There was a significant association between a 20% or greater reduction in
      HVPG and both histologic response and SVR. CONCLUSIONS: Treatment with
      combination peginterferon plus ribavirin may produce clinically significant
      reductions in HVPG in patients with CHC-related cirrhosis who achieve an SVR.

PMID- 17544879
TI  - Prevalence and predictors of esophageal varices in patients with primary biliary
      cirrhosis.
AB  - BACKGROUND & AIMS: Esophageal varices and bleeding are among the most feared
      complications of primary biliary cirrhosis (PBC). We aimed to determine the
      prevalence of esophageal varices in patients with PBC, to evaluate noninvasive
      markers of esophageal varices in this population, and to validate the results in
      an independent set of patients. METHODS: Data were collected on all patients with
      PBC seen for the first time at the University of Florida (study group) and at
      Case Western Reserve University hospitals (cross-validation group) during 7
      consecutive years. Logistic regression analysis was used to identify independent
      predictors of esophageal varices. The best cut-off values were calculated based
      on receiver operating characteristic curves. The diagnostic accuracy of the
      independent predictors of esophageal varices identified in the study group were
      retested in the cross-validation group. RESULTS: Of 210 patients with PBC seen at
      the University of Florida, 113 had an endoscopy and 49.6% (56 of 113) were found
      to have esophageal varices. After excluding 22 patients with a history of
      variceal bleeding, data on 91 patients were analyzed. Thirty-four patients had
      esophageal varices (37%). Multivariate analysis revealed that a platelet count of
      less than 140,000 (odds ratio, 7.6; 95% confidence interval, 1.6-37) and a Mayo
      risk score of 4.5 or greater (odds ratio, 10.6; 95% confidence interval, 1.8-62)
      were independent predictors of esophageal varices. The diagnostic accuracy of
      these predictors was confirmed in an independent set of patients. CONCLUSIONS:
      Among patients with PBC, a platelet count of less than 140,000 and/or a Mayo risk
      score of 4.5 or greater appears to identify those patients more likely to benefit
      from a screening endoscopy.

PMID- 17544880
TI  - The preoperative evaluation: an opportunity for education and other strategies to
      improve care.

PMID- 17544881
TI  - Patient understanding of the importance of beta-blocker use in the perioperative
      period.
AB  - OBJECTIVE: Perioperative beta-adrenergic blockade has been shown to decrease
      morbidity and mortality after noncardiac surgery. The objective of this study was
      to determine patient knowledge of the importance of perioperative beta-blockade
      in a population already taking chronic therapy and to assess the effectiveness of
      medical and surgical providers in patient education regarding these benefits.
      DESIGN: Survey. SETTING: Teaching hospital. PARTICIPANTS: One hundred twenty-six
      patients taking daily beta-blockers presenting to a preoperative medical
      evaluation clinic completed a 12-question survey that assessed their
      understanding of the potential benefit of taking the medication in the
      perioperative period. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Mean
      coronary artery disease risk factors per individual were 3.2 (standard deviation,
      1.5). Forty-nine percent indicated that beta-blockers are beneficial in the
      perioperative period. Of those identifying benefit, 8% recognized decrease in
      myocardial infarction or decrease in mortality as the reason. Sixty-nine percent
      of patients who identified perioperative benefit cited blood pressure control as
      the reason. This correlated to the 67% of the total sample who identified their
      indication for the medication as antihypertensive. Only 7% recalled their
      prescribing physician ever mentioning the beta-blocker in relation to surgery.
      The same percentage recalled their surgeon mentioning it in relation to the
      planned procedure. CONCLUSIONS: This study suggests low patient understanding of
      the potential importance and reasons for perioperative beta-blockade. Patients
      who recognized perioperative benefit identified antihypertensive versus
      cardioprotective effects. Clinicians can improve education of patients already
      taking daily beta-blockers regarding these potential benefits.

PMID- 17544882
TI  - Predictors of perioperative beta-blockade use in vascular surgery: a mail survey
      of United States anesthesiologists.
AB  - OBJECTIVES: It was hypothesized that anesthesiologists' decisions to provide
      perioperative beta-blockade during vascular surgery would be influenced more by
      physician factors than by those of their patients. DESIGN: Mail survey. SETTING:
      Case presentation. PARTICIPANTS: Four hundred thirty-nine anesthesiologists in
      the United States who responded to a survey. INTERVENTIONS: By using Microsoft
      Word Mail Merge (Microsoft, Redmond, WA), 6 factors in a hypothetical patient
      presenting for vascular surgery (sex, race, age, comorbidities, functional
      status, and magnitude of surgical stress) were randomly varied. MEASUREMENTS AND
      MAIN RESULTS: The response rate was 22%. Self-reported propensity to use beta
      blockade was significantly increased among anesthesiologists who worked in New
      England, among those who worked in larger hospitals, or who had received
      fellowship training. Among healthy patients, beta-blockers were more likely to be
      used for older than younger patients. Among sicker patients, however, the reverse
      was true. Heart rate triggers for beta-blockade use were higher than heart rates
      associated with improved outcomes in pivotal beta-blocker trials. CONCLUSIONS:
      Preferences for perioperative beta-blockade use in vascular surgery patients are
      influenced by anesthesiologists' demographics as well as patient comorbidities or
      degree of surgical stress. This finding suggests that efforts to increase
      perioperative beta-blockade in high-risk vascular patients face significant
      barriers from some groups of clinicians.

PMID- 17544883
TI  - Calcium antagonist verapamil and reperfusion injury of the heart.
AB  - OBJECTIVE: An experimental study to examine the effect of verapamil, given into a
      coronary artery, on reperfusion injury. DESIGN: The study was randomized but not
      blinded. SETTING: This study was conducted in the animal laboratory of the
      Department of Anesthesiology and Critical Care in an academic institution.
      PARTICIPANTS: The study was performed in an anesthetized open-chest pig model.
      INTERVENTIONS: Left anterior coronary artery (LAD) occlusion for 15 minutes
      followed by 90 minutes of reperfusion. Verapamil or saline was given into the LAD
      artery either at the time the coronary artery was occluded (ie, during acute
      severe ischemia or during the reperfusion period). MEASUREMENTS: LAD artery blood
      flow, regional myocardial function, and metabolism were assessed by the end
      systolic pressure length relationship, regional systolic shortening, postsystolic
      shortening, regional myocardial oxygen consumption, and local cardiac vein
      lactate. CONCLUSIONS: Verapamil given during ischemia resulted in a shorter
      period of regional myocardial stunning when compared with saline or verapamil
      during reperfusion. The difference in the verapamil strategies (ie, verapamil
      administered during ischemia versus verapamil during the reperfusion period) can
      probably be explained by a difference in the effective dose of the drug present
      in the heart at the time reperfusion started rather than the period of
      administration per se.

PMID- 17544884
TI  - The effects of vasoactive agents on flow through saphenous vein grafts during
      lower-extremity peripheral vascular surgery.
AB  - PURPOSE: The purpose of this study was to assess the effects of hemodynamic
      alterations on vein graft flow during peripheral vascular surgery. It was
      hypothesized that vasopressors can be administered without compromising flow
      through the vein grafts. SETTING: Tertiary care center, university medical
      center. STUDY DESIGN: Randomized placebo-controlled double-blinded study.
      METHODS: The effects of phenylephrine, epinephrine, milrinone, intravenous fluid,
      and placebo on newly constructed peripheral vein grafts were assessed in 60
      patients (12 patients in each of 5 groups). Systemic and central hemodynamics
      were measured by using intra-arterial and pulmonary artery catheters. Vein graft
      flow was measured by using a transultrasonic flow probe (Transultrasonic Inc,
      Ithaca, NY). RESULTS: Phenylephrine increased systemic mean blood pressure (mBP)
      (68.2-94.0 mmHg, p < 0.01), systemic vascular resistance (SVR) (1,091-1,696 dynes
      x sec x cm(-5), p < 0.001), and vein graft flow (39.5-58.9 mL/min, p < 0.01),
      whereas cardiac output remained unchanged. Epinephrine resulted in increased
      cardiac output (4.4-6.9 L/min, p < 0.01) and mBP (72.7-89.1 mmHg, p < 0.01),
      whereas vein graft flow was reduced in 6 of 12 patients. Intravenous fluid
      administration resulted in a relatively smaller increase in graft flow (37.6-46.0
      mL/min, p < 0.05), an increase in cardiac output, and an insignificant decrease
      in SVR. Other treatments had either little or no effect on vein graft flow.
      CONCLUSION: The study hypothesis was partly supported. Although both
      phenylephrine and epinephrine increased blood pressure, only the former increased
      vein graft flow in all patients. In conjunction with increases in graft flow
      after fluid administration, these data suggest that factors affecting vein graft
      flow are not just simply related to systemic hemodynamics.

PMID- 17544885
TI  - Increasing cardiac output by epinephrine after cardiac surgery: effects on
      indocyanine green plasma disappearance rate and splanchnic microcirculation.
AB  - OBJECTIVE: The effects of increasing cardiac output by epinephrine on indocyanine
      green plasma disappearance rate (ICG-PDR) and gastric mucosal PCO(2) (P(R)CO(2))
      were studied as indicators of splanchnic microcirculation. DESIGN: A prospective
      clinical study. SETTING: Intensive care unit of a university hospital.
      PARTICIPANTS: With ethics approval and written consent, 12 elective cardiac
      surgical patients (5 female, 7 male, 71 +/- 8 years) were studied. INTERVENTIONS:
      Patients underwent pulmonary artery and left atrial catheterization for clinical
      indications. Measurements were made at intensive care unit admission and 1 hour
      after (increased) epinephrine treatment. Mean epinephrine dose was changed from
      0.02 to 0.08 microg/kg/min. RESULTS: Heart rate significantly increased from 97
      +/- 11 to 106 +/- 12 beat/min. Central venous (10 +/- 3 v 10 +/- 4 mmHg) and left
      atrial (10 +/- 5 v 11 +/- 5 mmHg) pressures were unchanged. Cardiac index and
      stroke volume index significantly increased from 2.7 +/- 0.5 to 3.2 +/- 0.5
      L/min/m(2) and from 28 +/- 6 to 31 +/- 5 mL/m(2), respectively. Although systemic
      O(2) delivery and O(2) consumption significantly increased, ICG-PDR did not
      change significantly (ie, from 18.0% +/- 5.6% to 19.5% +/- 6.4% per minute).
      P(R)CO(2) and PCO(2) gap (difference between regional and end-tidal PCO(2))
      significantly increased from 5.4 +/- 1.0 to 5.9 +/- 1.1 kPa and 1.2 +/- 0.8 to
      1.5 +/- 0.7 kPa, respectively. CONCLUSION: Increasing cardiac output by
      epinephrine in patients after cardiac surgery was not associated with a change in
      flow-dependent liver function but a deterioration in gastric mucosal perfusion.

PMID- 17544886
TI  - Effects of preemptive enoximone on left ventricular diastolic function after
      valve replacement for aortic stenosis.
AB  - OBJECTIVE: Left ventricular (LV) hypertrophy is associated with increased
      diastolic chamber stiffness early after aortic valve replacement for valve
      stenosis. Enoximone, a phosphodiesterase III inhibitor, has been shown to improve
      myocardial contractility and relaxation when administered as a single dose after
      cardiac surgery. The present study investigated, by analysis of transmitral flow
      velocity patterns and end-diastolic pressure-area relations, whether enoximone
      administered before aortic valve surgery has an effect on LV diastolic
      properties. DESIGN: Prospective, randomized study. SETTING: Referral center for
      cardiothoracic surgery at a university hospital. PARTICIPANTS: Thirty-four
      patients undergoing aortic valve replacement for aortic stenosis. INTERVENTIONS:
      Patients in the enoximone group (n = 17) received a bolus dose of 0.35 mg/kg
      (0.15 mg/kg before aortic cross-clamping and 0.2 mg/kg added to the cardioplegic
      solution). Individual pressure-area relations (pulmonary capillary wedge pressure
      v left ventricular end-diastolic area) were obtained by using volume loading by
      leg elevation before and after surgery with closed chest. MEASUREMENTS AND MAIN
      RESULTS: The pressure-area relation on the pressure-area plot was shifted to the
      left after surgery, indicating decreased LV diastolic distensibility in the
      enoximone and control groups and providing evidence of decreased LV diastolic
      function. Indices of LV diastolic chamber stiffness, LV operating stiffness
      (K(LV)) derived from the deceleration time of early ventricular filling, and the
      constant of chamber stiffness (beta) derived from pressure-area relations were
      not different after enoximone treatment. Systolic LV function was unaltered after
      cardiac surgery in both groups. Analysis of changes in transmitral flow patterns
      identified an increased atrial filling fraction in enoximone-treated patients,
      suggesting increased atrial systolic function. The unaltered systolic pulmonary
      venous flow velocity compared with the decrease in the control group after volume
      loading further supports preservation of left atrial reservoir function with
      enoximone in the absence of evidence for decreased LV stiffness. CONCLUSION:
      Preemptive enoximone did not change LV diastolic function based on diastolic
      filling patterns or LV stiffness indices (K(LV) and beta) derived from Doppler
      early filling deceleration time and pressure-area relations. Doppler data
      suggested improvement of left atrial systolic function and preservation of left
      atrial reservoir function with enoximone.

PMID- 17544887
TI  - Transesophageal tissue Doppler echocardiography for evaluation of myocardial
      function during aortic valve replacement.
AB  - OBJECTIVE: Tissue Doppler imaging is an evolving ultrasound technology that,
      compared with traditional echocardiography, promises reduced subjectivity in the
      assessment of myocardial performance and contributes new information on
      myocardial function. The aim of this study was to evaluate the feasibility of
      transesophageal tissue Doppler imaging in the setting of aortic valve
      replacement. DESIGN: Feasibility study. SETTING: Aarhus University Hospital,
      Denmark. PARTICIPANTS: Twelve patients with isolated aortic valve stenosis or
      combined ischemic cardiomyopathy and aortic valve stenosis scheduled for elective
      aortic valve replacement were included. INTERVENTION: Transgastric short-axis
      recordings of the left ventricular anterior wall were performed using Vivid-7
      technology (GE Healthcare, Horten, Norway) with activated tissue Doppler imaging
      before sternotomy, at intervals during progressive withdrawal of cardiopulmonary
      bypass, and within 1 hour after transfer to the postoperative care unit. Data
      were postprocessed for assessment of systolic radial function with the tissue
      Doppler modalities, tissue velocity, end-systolic strain rate, and strain by
      using dedicated software. RESULTS: Accurate tissue Doppler data were obtained for
      all patients at baseline and postoperatively. During the gradual loading of the
      left ventricle, velocity measurements were all obtained accurately, whereas 8% to
      25 % of strain and strain-rate measurements were considered unreliable.
      Immediately after cardioplegia, 33% to 58% of measurements were unreliable.
      CONCLUSIONS: Transesophageal tissue Doppler is feasible in the intraoperative
      setting, although unreliable data acquisition occurs during cardiopulmonary
      bypass. Tissue Doppler is a promising quantitative tool for monitoring of
      myocardial function within minutes and may also reveal new information on
      myocardial function in patients undergoing thoracic surgery.

PMID- 17544888
TI  - Mild hypercapnia after uncomplicated heart surgery is not associated with
      hemodynamic compromise.
AB  - OBJECTIVE: The aim of this study was to examine the effects of small changes in
      PaCO(2) on hemodynamic parameters after uncomplicated heart surgery with
      cardiopulmonary bypass. DESIGN: This was a prospective, randomized crossover
      study. SETTING: A large academic medical center. PARTICIPANTS: Twenty-four
      subjects who were scheduled for elective cardiac surgery were enrolled in this
      study. INTERVENTIONS: Each subject underwent the normal procedures that are
      associated with cardiac surgery. General anesthesia, including muscle relaxation,
      were continued in the immediate postoperative period. Measured tidal volumes and
      minute ventilation were kept constant for the duration of the study. Target
      PaCO(2) concentrations of 30, 40, and 50 mmHg were achieved by adding varying
      amounts of exogenous CO(2) gas to the inhaled oxygen. Various measurements were
      made at each target PaCO(2), including cardiac index, mixed venous oxygen
      saturation, blood pressure, heart rate, and pulmonary artery pressure.
      MEASUREMENTS AND MAIN RESULTS: Twenty-four patients were enrolled. Seven were
      withdrawn before commencement of the study. The cardiac index increased when the
      PaCO(2) was increased from 30 to 40 mmHg (p < 0.001) and remained unchanged
      between 40 and 50 mmHg. Mixed venous oxygen saturation increased (p < 0.001) with
      elevations in PaCO(2) up to 50 mmHg and decreased again when the PaCO(2) was
      returned to 30 mmHg. The blood pressure decreased (p < 0.001) with increasing
      PaCO(2). The pulmonary pressure increased (p < 0.001) with elevations in PaCO(2).
      No patient became hemodynamically unstable or had any arrhythmias. CONCLUSION:
      The findings of this study suggest that unless there is a specific
      contraindication to mild hypercapnia, such as pulmonary hypertension or
      hemodynamic instability, concerns about mild respiratory acidosis should not
      prevent weaning of sedation and mechanical ventilation after uncomplicated heart
      surgery.

PMID- 17544889
TI  - Effects of alveolar recruitment on arterial oxygenation in patients after cardiac
      surgery: a prospective, randomized, controlled clinical trial.
AB  - OBJECTIVE: Pulmonary atelectasis and hypoxemia remain considerable problems after
      cardiac surgery. The objective of this study was to determine the efficacy of
      consecutive vital capacity maneuvers (C-VCMs) to improve oxygenation in patients
      after cardiac surgery. STUDY DESIGN: Randomized, controlled clinical trial.
      SETTING: Tertiary referral teaching center. PARTICIPANTS: Ninety-five patients
      requiring elective cardiac surgery with cardiopulmonary bypass (CPB).
      INTERVENTION: Patients were randomly allocated to either C-VCM or control groups.
      In the C-VCM group, lung inflation at pressure of 35 cmH(2)O was sustained for 15
      seconds before separation from CPB and at 30 cmH(2)O for 5 seconds after
      admission to the intensive care unit (ICU). MEASUREMENTS AND MAIN RESULTS: The
      primary outcome was the ratio of arterial oxygen tension to inspired oxygen
      fraction measured at the following predetermined time intervals: after induction
      of anesthesia, 15 minutes after separation from CPB, after admission to the ICU,
      after 3 hours of positive-pressure ventilation, after extubation, and before ICU
      discharge. C-VCM resulted in better arterial oxygenation extending from the
      immediate postoperative period to approximately 24 hours after surgery at the
      time of ICU discharge. There were no significant adverse events related to C-VCM
      application. CONCLUSION: C-VCM is an effective method to reduce hypoxemia
      associated with the formation of atelectasis after cardiac surgery with CPB.

PMID- 17544890
TI  - Early continuous venovenous hemodialysis in dialysis-dependent patients after
      cardiac surgery: safety and efficacy.
AB  - OBJECTIVES: The present study assessed the safety and efficacy of continuous
      venovenous hemodialysis (CVVHD) early after cardiac surgery. DESIGN:
      Retrospective database and medical record review. SETTING: University teaching
      hospital. PARTICIPANTS: Forty-five dialysis-dependent patients who underwent
      cardiac surgery with cardiopulmonary bypass. INTERVENTIONS: CVVHD was begun
      postoperatively after confirmation of hemostasis, irrespective of circulatory
      status. In the last 5 patients, the ratio of extravascular lung water (EVLW) to
      intrathoracic blood volume (ITBV) was measured using a single-indicator
      thermodilution catheter and compared with patients of normal renal function
      undergoing cardiac surgery. MEASUREMENTS AND MAIN RESULTS: CVVHD was started at 4
      hours after ICU admission. The maximum decrease in blood pressure within 60
      minutes after initiation of CVVHD was 11 +/- 9 mmHg in the unstable hemodynamics
      group (defined as patients who required continuous intravenous adrenaline or
      intra-aortic balloon pump on admission to the ICU [n = 15]) and 7 +/- 8 mmHg in
      the stable hemodynamics group (n = 30, not significant). Circulatory status and
      oxygenation improved significantly 12 hours after CVVHD initiation in the
      unstable hemodynamics group. Blood volume from the chest tube did not increase
      after CVVHD. Early mortality (2.2%) was lower than that reported previously. The
      EVLW/ITBV ratio after ICU admission in dialysis-dependent patients was
      significantly higher than in patients with normal renal function. CONCLUSIONS:
      Early CVVHD after cardiac surgery in dialysis-dependent patients was safe and
      effective. There was no associated increased postoperative bleeding or
      hemodynamic instability. Fluid removal improved respiratory status, particularly
      in patients requiring circulatory assistance, and overall early morality rates
      were lower that those previously published.

PMID- 17544891
TI  - Establishing extracorporeal membrane oxygenation in a university clinic: case
      series.
AB  - OBJECTIVES: Although extracorporeal membrane oxygenation (ECMO) is well
      established for respiratory failure in neonates, application in adults is still
      considered controversial. The survival of patients with acute respiratory
      distress syndrome and ECMO therapy is 50% to 70%. DESIGN: A retrospective
      analysis of 10 patients, who were placed on ECMO from September 2004 to December
      2005, was performed. SETTING: University clinic. INTERVENTIONS: Venoarterial ECMO
      was established in 7 patients, venovenous ECMO in 2 patients, and combined
      venoarterial and venovenous ECMO in 1 patient. MEASUREMENTS AND MAIN RESULTS:
      Indications were pneumonia, acute respiratory distress syndrome, near drowning,
      pericardial tamponade with shock lung, right-heart failure after heart
      transplantation, shock lung after cardiopulmonary resuscitation, and right-heart
      failure in chronic thromboembolic pulmonary hypertension. Median maintenance of
      ECMO therapy was 56.5 hours (range, 36-240). The median Murray score was 3.3 for
      survivors and 4 for nonsurvivors. Overall mortality was 30%; 70% were weaned from
      ECMO and survived until discharge. Median pre-ECMO risk for fatal outcome
      according to Hemmila was 0.43 for survivors and 0.92 for nonsurvivors (p < 0.02).
      In 2 cases, surgical reintervention was necessary because of bleeding in one, and
      a side switch of the cannulae had to be performed because of femoral venous
      thrombosis in the other. CONCLUSIONS: ECMO has been shown to be a successful
      therapy for acute respiratory distress syndrome when conventional strategies have
      failed. Pre-ECMO risk assessment may be useful in the evaluation of patients.

PMID- 17544892
TI  - Atrial fibrillation after aortic arch repair requiring deep hypothermic
      circulatory arrest: incidence, clinical outcome, and clinical predictors.
AB  - OBJECTIVE: To delineate the incidence, outcome impact, and clinical predictors of
      atrial fibrillation (AF) after adult aortic arch repair requiring deep
      hypothermic circulatory arrest (AAR-DHCA) AIMS: To determine the incidence of AF
      after AAR-DHCA, to determine whether AF after AAR-DHCA affects mortality or stay
      in the intensive care unit (ICU), to determine multivariate predictors for AF
      after AAR-DHCA, and to determine whether aprotinin protects against AF after AAR
      DHCA. STUDY DESIGN: Retrospective and observational. STUDY SETTING: Single large
      university hospital. PARTICIPANTS: All adults undergoing AAR-DHCA in 2000 and
      2001. MAIN RESULTS: The cohort size was 144. Antifibrinolytic exposure was 100%,
      aprotinin 66% and aminocaproic acid 34%. The incidence of AF was 34.0%. AF was
      not significantly associated with increased mortality or prolonged ICU stay.
      Advanced age was a multivariate risk factor for AF. Lower temperature nadir
      during DHCA was protective against postoperative AF. Aprotinin had no
      demonstrable effect on AF after AAR-DHCA. CONCLUSIONS: AF after AAR-DHCA is
      common but does not independently increase mortality or ICU stay. The risk of AF
      after AAR-DHCA increases with age but decreases with the degree of hypothermia
      during DHCA. Aprotinin does not appear to affect the risk of AF after AAR-DHCA.

PMID- 17544893
TI  - Effects of pericardial lidocaine on hemodynamic parameters and responses in dogs
      anesthetized with midazolam and fentanyl.
AB  - OBJECTIVE: Tachycardia during anesthesia should be avoided, especially during off
      pump coronary artery bypass graft surgery. Decreasing heart rate without reducing
      cardiac contractility is an ideal goal. To achieve this, the authors attempted to
      block the cardiac nerves by pericardial administration of local anesthetic.
      DESIGN: A prospective study. SETTING: A laboratory. PARTICIPANTS: Anesthetized,
      mechanically ventilated dogs (n = 69). INTERVENTIONS: The pericardial space was
      infused with 2.5 or 5 mL of 1% lidocaine, 5 mL of 2% lidocaine, or normal saline
      solution. The hemodynamic changes and the cardiac responses to atropine or
      isoproterenol were measured during cardiac nerve blockade. To examine the
      inhibitory action of pericardial lidocaine on arrhythmias, an electrical
      fibrillator was installed. Furthermore, the blood level of lidocaine was
      measured. MEASUREMENTS AND MAIN RESULTS: Pericardial injection of lidocaine
      significantly decreased heart rate without a change in stroke volume. Under
      pericardial lidocaine, the tachycardia response to isoproterenol was similar to
      that observed without pericardial lidocaine, but response to atropine was
      significantly reduced. Pericardial lidocaine increased the voltage thresholds for
      inducing arrhythmias and ventricular fibrillation. Intravenous injection of
      lidocaine elevated the plasma concentration of lidocaine immediately, whereas the
      plasma concentration peaked at 10 minutes after pericardial administration.
      CONCLUSIONS: Pericardial lidocaine (1) decreased heart rate without affecting
      stroke volume, (2) preserved the tachycardiac response to isoproterenol but
      completely blocked the response to atropine, and (3) increased the voltage
      thresholds for arrhythmias and ventricular fibrillation induced by an electrical
      fibrillator. These results suggest that pericardial lidocaine may be useful for
      controlling heart rate during off-pump coronary artery bypass graft surgery.

PMID- 17544894
TI  - Treating ischemic left ventricular dysfunction with hypertonic saline
      administered after coronary occlusion in pigs.
AB  - OBJECTIVE(S): The effects of hypertonic saline on ventricular function are
      controversial, whether it is increasing contractility or preload. There are no
      data, however, on the influence of hypertonic saline in a stunned myocardium.
      DESIGN: This study was prospective and randomized in order to analyze the effects
      of hypertonic saline solution (7.5%) on myocardial function and systemic
      hemodynamics in a porcine model of ischemia and reperfusion. SETTING: A
      university teaching hospital, animal research laboratory. PARTICIPANTS: Twelve
      adult domestic swine. INTERVENTIONS: Myocardial stunning was produced by the
      complete occlusion of the proximal left anterior descending artery for 15 minutes
      followed by reperfusion. Five minutes after reperfusion, the animals were
      assigned to receive 4 mL/kg of hypertonic saline (n = 7) or normal saline (n = 5)
      over 10 minutes. Pressure-tipped catheters were placed in the left ventricular
      cavity and aorta. The dimensions of the left ventricle were measured with
      ultrasonic microcrystals. Cardiac output was measured with transit time
      ultrasound. Data were recorded continuously and compared before the occlusion, 5
      minutes after reperfusion, and at the end of the infusion. MEASUREMENTS AND MAIN
      RESULTS: Compared with baseline, ventricular function was significantly depressed
      after left anterior descending artery occlusion. Left ventricular dP/dT and its
      end-systolic pressure-volume slope decreased (38% and 52%, respectively; p <
      0.05), with a concomitant increase in systemic vascular resistance. The
      administration of hypertonic saline significantly improved left ventricular
      function (Emax 1,422 +/- 198 mmHg/mL, and dP/dT 3.2 +/- 0.4 mmHg/s v normal
      saline group values of 1,156 +/- 172 and 2.5 +/- 0.5, respectively; p < 0.05),
      cardiac output (2.5 +/- 0.5 v 1.84 +/- 0.4 L/min, p < 0.05), and lowered systemic
      vascular resistance (from 28.8 +/- 2.3 to 23.5 +/- 1.4, p < 0.05), with no
      significant changes with normal saline administration. CONCLUSIONS: After
      transient myocardial ischemia, hypertonic saline administered over a short period
      of time acts as an inodilator by increasing contractility while simultaneously
      lowering systemic vascular resistance.

PMID- 17544895
TI  - Pathophysiology of verapamil overdose: new insights in the role of insulin.

PMID- 17544896
TI  - Fatal fibrinolysis during orthotopic liver transplantation in patients receiving
      solvent/detergent-treated plasma (Octaplas).

PMID- 17544897
TI  - Administration of amiodarone into the aortic root for persistent ventricular
      fibrillation after aortic valve replacement.

PMID- 17544898
TI  - Superior vena cava syndrome after cardiac surgery: early treatment by
      percutaneous stenting.

PMID- 17544899
TI  - Misplacement of a guidewire diagnosed by transesophageal echocardiography.

PMID- 17544900
TI  - Inferior thyroid artery injury after attempts of internal jugular venous
      catheterization.

PMID- 17544901
TI  - "Epi-neck" scanning: another use for echocardiography?

PMID- 17544902
TI  - Anesthetic management of a patient with Niemann-Pick type B disease undergoing
      cardiac surgery.

PMID- 17544903
TI  - Resection of metastatic right ventricular leiomyosarcoma: the role of
      transesophageal echocardiography.

PMID- 17544904
TI  - Massive prosthetic valve thrombus in a patient with idiopathic hypereosinophilic
      syndrome.

PMID- 17544905
TI  - Percutaneous coronary interventions and antiplatelet therapy in the perioperative
      period.

PMID- 17544906
TI  - Case 3-2007: successful cardiac surgery in a "pulmonary cripple" without thoracic
      epidural anesthesia.

PMID- 17544907
TI  - Pro: use of colloids in cardiac surgery.

PMID- 17544908
TI  - Con: use of colloids in cardiac surgery.

PMID- 17544909
TI  - A transesophageal echocardiographic finding with a difference.

PMID- 17544910
TI  - A triple-lumen aorta: an unusual manifestation of complex aortic pathology
      associated with crack cocaine abuse.

PMID- 17544911
TI  - Internal jugular venous catheter malposition.

PMID- 17544912
TI  - Storage lesion in intraoperative autologous whole blood.

PMID- 17544914
TI  - Opioids and cardioprotection: the impact of morphine and fentanyl on recovery of
      ventricular function after cardiopulmonary bypass.

PMID- 17544916
TI  - An aid to awake bronchoscopic nasal intubation.

PMID- 17544917
TI  - Unrecognized nasal foreign body: potential consequences.

PMID- 17544918
TI  - Bispectral index monitoring during aortic arch repair.

PMID- 17544919
TI  - Is routine placement of a pulmonary artery catheter essential?

PMID- 17544920
TI  - Preoperative placement of retreivable inferior vena cava filters in bariatric
      surgery.
AB  - BACKGROUND: Postoperative pulmonary embolism (PE) is a major source of mortality
      after bariatric surgery. In conjunction with pharmacologic thromboprophylaxis,
      lower extremity pneumatic compression devices, and early ambulation, preoperative
      placement of a retrievable inferior vena cava (IVC) filter may reduce the risk of
      thromboembolic complications. METHODS: From June 2003 to October 2005, 652
      patients underwent mini-open Roux-en-Y gastric bypass. Of the 652 patients, 557
      were women and 95 were men. The mean patient age was 40.7 +/- 3.6 years (range 18
      67), mean body mass index was 44.7 +/- 4.6 kg/m(2) (range 35-78), and mean
      operative time was 60.2 +/- 5.3 minutes (range 42-79). The high-risk PE group
      consisted of 27 patients (4.1%; 9 men and 18 women) who received preoperative
      retrievable IVC filters placed by the interventional radiology staff 2 hours
      before bypass surgery. Their mean age was 47 +/- 4.4 years (range 31-66) and mean
      body mass index 48.7 +/- 4.2 kg/m(2) (range 38-75). The indications for filter
      placement were previous deep vein thrombosis/PE, thrombophlebitis, a
      hypercoagulable state, pulmonary hypertension, an inability to ambulate, a body
      mass index >65 kg/m(2), and the presence of severe sleep apnea. The filters were
      removed 18.2 +/- 2 days (range 15-21) postoperatively. RESULTS: All 27 patients
      who received a prophylactic IVC filter tolerated the procedure well, without
      major complications. One retrievable filter was not removed because of prolonged
      hospitalization secondary to small bowel obstruction. No thromboembolic
      complications occurred in this high-risk group. CONCLUSION: Preoperative
      placement of retrievable IVC filters is a safe measure for the prophylaxis of PE
      in high-risk bariatric patients. The filters can be placed efficiently just
      before surgery, and most filters can be removed 2-3 weeks postoperatively.
      Additional investigation is necessary to prove the effectiveness of retrievable
      IVC filters in bariatric surgery.

PMID- 17544921
TI  - Inferior vena cava filter placement for pulmonary embolism risk reduction in
      super morbidly obese undergoing bariatric surgery.
AB  - BACKGROUND: Pulmonary embolism (PE) is a leading cause of mortality after
      bariatric surgery. We evaluated inferior vena cava (IVC) filter use for PE risk
      reduction in high-risk super morbidly obese bariatric surgery patients. METHODS:
      IVC filters were inserted according to the patient's risk factors, including
      immobility, previous deep venous thrombosis (DVT)/PE, venous stasis, and
      pulmonary compromise. All filters were placed concomitant to bariatric surgery
      and were placed through a right internal jugular vein access site. We analyzed
      the prospectively collected data from this cohort and evaluated the incidence of
      PE and complications. RESULTS: Since April 2003, 41 patients (12 men and 29
      women) with a mean age of 47.3 +/- 10.0 years and body mass index of 64.2 +/- 12
      kg/m2 (range 47-105) underwent IVC filter placement. These and all other patients
      underwent standard DVT/PE risk reduction measures. All IVC filter patients had
      one or more significant risk factors for thromboembolic events. No instances of
      PE were documented, although 1 patient experienced DVT, and no immediate or late
      complications related to filter placement occurred. One patient, with a body mass
      index of 105 kg/m2, died secondary to rhabdomyolysis after an extended procedure.
      The average filter placement time was 34.3 +/- 9 minutes. CONCLUSION: IVC filter
      placement for PE risk reduction is safe and feasible in the super morbidly obese.
      Our data have shown that the filters can be placed expeditiously and with minimal
      morbidity concomitant with bariatric surgery. In this limited series, IVC filter
      placement was associated with no PE. Additional studies are needed to confirm the
      efficacy of IVC filter placement for PE risk reduction and related mortality in
      the super morbidly obese.

PMID- 17544923
TI  - Antecolic versus retrocolic alimentary limb in laparoscopic Roux-en-Y gastric
      bypass: a comparative study.
AB  - BACKGROUND: Laparoscopic Roux-en-Y gastric bypass (LRYGB) has become the most
      common surgical treatment for morbid obesity. Intestinal obstruction and internal
      hernias are complications more commonly observed after LRYGB than after open
      RYGB. The aim of this study was to evaluate the incidence of these complications
      in patients who had undergone LRYGB using an antecolic versus a retrocolic
      technique. METHODS: From August 2001 to August 2005, LRYGB was performed in 754
      patients. The retrocolic and antecolic technique was used in 300 and 454
      consecutive patients, respectively. The mean patient age was 37 +/- 10 years, and
      552 of the patients (73%) were women. The mean preoperative body mass index was
      41.3 +/- 5 kg/m2. The median follow-up was 16 months. RESULTS: During follow-up,
      36 patients (4.7%) underwent surgical exploration secondary to intestinal
      obstruction. This complication was observed in 28 (9.3%) and 8 (1.8%) patients in
      the retrocolic and antecolic technique groups, respectively (P <.001). In the
      retrocolic technique group, an internal hernia developed in 24 patients compared
      with 3 patients in the antecolic technique group. On multivariate analysis, the
      retrocolic technique was identified as a risk factor (P <.001). CONCLUSION: A
      greater incidence of intestinal obstruction and internal hernia was observed in
      the retrocolic technique group than in the antecolic technique group undergoing
      LRYGB. The results of our study have shown that the use of the retrocolic
      technique is a risk factor for intestinal obstruction after LRYGB.

PMID- 17544924
TI  - Endoscopic injection of fibrin sealant in repair of gastrojejunostomy leak after
      laparoscopic Roux-en-Y gastric bypass.
AB  - BACKGROUND: A leak at the gastrojejunostomy (GL) is a potentially life
      threatening complication of laparoscopic Roux-en-Y gastric bypass. Because
      operative repair of acute leaks is usually unsuccessful, these patients often
      require prolonged hospitalization with drainage and parenteral hyperalimentation.
      METHODS: A total of 354 consecutive patients underwent primary laparoscopic Roux
      en-Y gastric bypass at a New Jersey hospital. We reviewed the records of all
      patients who had GLs and were treated using either endoscopic injection of fibrin
      sealant (EIFS) at the site of the GL or open surgical drainage. RESULTS: A GL
      occurred in 8 patients (2.25%). Of these 8 patients, 3 with unstable vital signs
      underwent exploratory laparotomy and drainage, and 5 clinically stable patients
      with GL were treated nonoperatively and subsequently underwent EIFS into the GL.
      In the operative group, the mean duration of treatment between the identification
      of the GL and closure was 24 days, with a mean length of stay of 66 days. Of the
      5 patients in the EIFS group, 1 required 2 injections within 11 days to achieve
      successful closure and 4 underwent closure of the GL within 2 days after
      injection, with a mean length of stay of 13.5 days. No complications or
      recurrences developed in the EIFS group. CONCLUSION: EIFS was successful in the 5
      consecutive patients who developed a GL after laparoscopic Roux-en-Y gastric
      bypass. This technique reduces the morbidity and length of stay associated with
      open drainage. EIFS should be used as the primary treatment in stable patients
      with controlled GLs after major gastrointestinal operations.

PMID- 17544925
TI  - Autonomic cardiovascular control in methyl-CpG-binding protein 2 (Mecp2)
      deficient mice.
AB  - Methyl-CpG-binding protein 2 is a transcription factor that is involved in gene
      silencing. It is mutated in the majority of cases of Rett syndrome. This X-linked
      neurodevelopmental disorder is reported to involve abnormalities in autonomic
      cardiovascular regulation. As an initial step in understanding the basis for
      these abnormalities we have characterized autonomic cardiovascular function in
      Mecp2 deficient mice. Arterial pressure waves were recorded in freely moving
      animals using telemetry. Baseline blood pressure and pulse interval (PI) as well
      as indices of heart rate variability (HRV): standard deviation of PI (SDNN),
      range encompassing 90% of PIs (PI90) and standard deviation of adjacent PIs
      (SDSD) were similar in Mecp2(+/+) and Mecp2(+/-) animals. Spectral analysis of
      mean arterial pressure (MAP) and PI in the frequency domain showed similar
      relative power in low frequency 1 (LF1, 08-0.4 Hz), low frequency 2 (LF2, 0.4-1.0
      Hz), middle frequency (MF, 1-3 Hz) and high frequency (HF, 3.0-10.0 Hz) bands.
      Autonomic blockade with atropine or propranolol as well as elevation in ambient
      temperature to 32 degrees C resulted in changes in blood pressure, PI and HRV
      that did not differ between the strains. Atropine, propranolol and elevated
      temperature resulted in similar changes in both MAP and PI spectral power.
      Baroreceptor function was tested using intravenous injections of nitroprusside
      followed by phenylephrine. Maximum gain was not different. These results do
      reveal any disturbance of autonomic cardiovascular regulation in the Mecp2
      deficient mouse genotype.

PMID- 17544926
TI  - Genetic heterogeneity, evolution and recombination in emerging G9 rotaviruses.
AB  - G9 rotavirus is recognized as the emerging genotype spreading around the world.
      The rapidly increasing detection of this virus in association with the genetic
      heterogeneity raises questions regarding its origin and epidemiological
      importance. A total of 380 sequences of rotavirus G9 strains including our
      sequence data from Vietnam and Japan, which were detected from 1983 to 2006 in
      five different continents, were collected from GenBank to investigate their
      heterogeneity and evolution. A novel nomenclature for G9 rotaviruses is proposed,
      in which these viruses are clustered into 6 lineages with 11 sublineages.
      Multiple amino acid substitutions of VP7 specific for lineages and sublineages
      were found. Interestingly, six short amino acid motifs correctly defined
      phylogenetic lineages and sublineages. Another interesting finding was the
      identification of recombinant G9 rotavirus, bearing different genotype sequence.
      In view of rotavirus evolution, this report is an additional evidence to support
      the notion that there might exist a genomic relatedness between human and porcine
      rotaviruses.

PMID- 17544927
TI  - Spontaneous duplications in diploid Saccharomyces cerevisiae cells.
AB  - The duplication of DNA sequences is a powerful determinant of genomic plasticity
      and is known to be one of the key factors responsible for evolution. Recent
      genomic sequence data demonstrate the abundance of duplicated genes in all
      surveyed organisms. Over the past years, experimental systems were adequately
      designed to explore the molecular mechanisms involved in their formation in
      haploid Saccharomyces cerevisiae strains. To obtain a more global and accurate
      view of the events leading to DNA sequence duplications, we have selected and
      characterized duplication occurrences in diploid S. cerevisiae cells. The
      molecular analysis showed that two other predominant ways lead to duplication in
      this context: formation of extra chimeric chromosomes and non-reciprocal
      translocation events. Moreover, we demonstrated that these two types of
      rearrangements are RAD52 independent and therefore that homologous recombination
      plays no part in their formation. Finally, our results show the multiplicity of
      mechanisms involved in duplication events and provide the first experimental
      evidence that these mechanisms might be ploidy dependent.

PMID- 17544930
TI  - Photodynamic therapy with lasers and intense pulsed light.
AB  - For many physicians, photodynamic therapy has become a routine part of using
      lasers and light sources to improve the outcomes of photorejuvenation therapies.
      Aminolevulinic acid photodynamic therapy (ALA-PDT) was first used in the
      treatment of actinic keratoses in the United States. It quickly became evident
      that PDT therapy for actinic keratoses had an additional cosmetic benefit, and
      clinical trials have confirmed the effectiveness of ALA-PDT in treating
      photorejuvenation with or without associated actinic keratoses. This article
      reviews the peer-reviewed literature regarding ALA-PDT in photorejuvenation and
      also summarizes the author's own techniques in using this new and exciting
      therapeutic method.

PMID- 17544928
TI  - Synergistic action of the Saccharomyces cerevisiae homologous recombination
      factors Rad54 and Rad51 in chromatin remodeling.
AB  - Rad54, a member of the Swi2/Snf2 protein family, works in concert with the RecA
      like recombinase Rad51 during the early and late stages of homologous
      recombination. Rad51 markedly enhances the activities of Rad54, including the
      induction of topological changes in DNA and the remodeling of chromatin
      structure. Reciprocally, Rad54 promotes Rad51-mediated DNA strand invasion with
      either naked or chromatinized DNA. Here, using various Saccharomyces cerevisiae
      rad51 and rad54 mutant proteins, mechanistic aspects of Rad54/Rad51-mediated
      chromatin remodeling are defined. Disruption of the Rad51-Rad54 complex leads to
      a marked attenuation of chromatin remodeling activity. Moreover, we present
      evidence that assembly of the Rad51 presynaptic filament represents an obligatory
      step in the enhancement of the chromatin remodeling reaction. Interestingly, we
      find a specific interaction of the N-terminal tail of histone H3 with Rad54 and
      show that the H3 tail interaction domain resides within the amino terminus of
      Rad54. These results suggest that Rad54-mediated chromatin remodeling coincides
      with DNA homology search by the Rad51 presynaptic filament and that this process
      is facilitated by an interaction of Rad54 with histone H3.

PMID- 17544931
TI  - Bipolar radiofrequency for facial rejuvenation.
AB  - Combined approaches using light and radiofrequency represent an innovative
      approach to whole body rejuvenation. Synergistic results using combined
      modalities are a major advantage of this technology. In addition, by using lower
      levels of light energy, darker skin phenotypes can be treated with a lower risk
      for pigment dyschromia and scarring.

PMID- 17544932
TI  - Monopolar radiofrequency skin tightening.
AB  - The development of nonablative monopolar capacitive radiofrequency technology
      (ThermaCool System, Thermage, Inc., Hayward, California) has contributed to the
      noninvasive trend in facial skin rejuvenation. In contrast to traditional
      ablative resurfacing techniques, the ThermaCool System protects the skin surface
      from injury while selectively heating the underlying dermis. Preservation of
      epidermal integrity minimizes recovery and the risk of complications. Published
      clinical evidence documents the efficacy of monopolar capacitive radiofrequency
      skin tightening and supports its use for mild to moderate facial skin laxity and
      rhytides. Currently, monopolar capacitive radiofrequency represents the gold
      standard of treatments designed to tighten skin in a noninvasive fashion.

PMID- 17544933
TI  - Cervical facial skin tightening with an infrared device.
AB  - Improvement of facial and cervical skin laxity has been difficult to achieve
      without surgical procedures. A device called the Titan, (Cutera, Inc., Brisbane,
      California) uses infrared light to volumetrically heat the dermis. It is designed
      to thermally induce collagen contraction, with subsequent collagen remodeling and
      neocollagen synthesis. The epidermis is protected via pre-, parallel, and post
      treatment cooling. Because there is minimal to no discomfort during the
      procedure, no anesthesia is necessary. With this device, improvements in skin
      laxity and facial and neck contours have been achieved. Results can vary,
      however. This variation may be caused by patient selection variability and
      differences in technique. This article presents an effective approach to patient
      selection, evaluation, and treatment planning, and a detailed treatment protocol.

PMID- 17544934
TI  - Erbium:YAG laser resurfacing using a novel portable device.
AB  - Laser resurfacing of facial rhytids has become a popular treatment for many
      patients who have wrinkles, photodamage, and acne scarring. Erbium:YAG laser
      resurfacing has emerged as one of the safer, more effective methods of facial
      rejuvenation and its increasing popularity has led to its widespread use for
      resurfacing. However, size and high initial and maintenance cost are among the
      problems with currently available laser devices. The LightPod portable Erbium:YAG
      laser from Aerolase offers a new paradigm for more cost effective means of
      performing ablative resurfacing with reduced initial and maintenance cost and the
      ease of portability with significantly reduced size and weight. The objective of
      this pilot study was to analyze the efficacy of The LightPod Erbium:YAG laser in
      different skin types for various indications.

PMID- 17544935
TI  - Closed meloplication percutaneous cable suture technique.
AB  - The aging midface is caused by a complex process of soft tissue volume loss,
      gravitational changes, and attenuation of the ligaments involved. This process
      results in a skeletonized appearance and elongation of the eyelid cheek complex
      and a medial and inferior descent of the malar fat pads. Standard facelifting
      techniques have been unsuccessful in addressing these issues. The authors
      describe the technical aspects of the closed meloplication percutaneous cable
      suture technique in detail, evaluate 55 cases as a retrospective chart review
      over a 5-year period, and address the complication rate.

PMID- 17544936
TI  - Midface barbed suture lift.
AB  - Barbed suture lifting is not comparable to and should not be presented as an
      alternative to a face-lift. It should be viewed as a temporizing procedure that
      can and should be maintained until the aging appearance in a patient demands a
      different approach. Much more experience is need with retightening of these
      procedures. New variations on self-engaging sutures are on the horizon. These and
      other new sutures represent a continued evolution in this technology.

PMID- 17544937
TI  - Minimally invasive midfacial rejuvenation: combining thread-lift and
      lipotransfer.
AB  - Minimally invasive procedures that offer reduced downtime are on the rise in
      aesthetic facial surgery, and it is essential that these newer technologies
      undergo critical assessment in the hands of well-trained facial plastic surgeons.
      The combination of lipotransfer and thread-lift represents a new modality to
      address midfacial aging. Specific technical considerations are provided in this
      article, and vigorous management of patient expectations is recommended. These
      techniques have a moderate learning curve without significant morbidities.
      Despite patient satisfaction, surgeon satisfaction will only be realized as long
      term results are better understood.

PMID- 17544938
TI  - Autologous fat augmentation: a perfect fit in new and emerging technologies.
AB  - The focus of recent cosmetic surgery is on the replacement of lost facial volume.
      Much of aging is a complex set of changes, including bone loss, muscle atrophy,
      and subcutaneous loss. For this reason, autologous fat augmentation is the
      perfect fit in the realm of new and emerging technologies. Although not
      necessarily a "new" technology, many advances have been made in the harvesting
      and infiltration of the fat, yielding much more consistent and long-lasting
      results. It also has the closest attributes of the "ideal filler."

PMID- 17544939
TI  - Fractionated photothermolysis: the Fraxel 1550-nm glass fiber laser treatment.
AB  - The carbon dioxide laser has been long considered to be the gold standard for
      cosmetic skin resurfacing. Although Fraxel laser treatment results are in general
      not as dramatic as with carbon dioxide lasering, they still are remarkable,
      measurable, and consistent. The lack of downtime and the decreased risk for
      complications make Fraxel laser treatment a particularly attractive choice for
      patients. Although a carbon dioxide laser cannot be used on the neck because of
      the risks of scarring, the Fraxel laser treatment is an excellent modality for
      reducing neck wrinkling and upper chest hyperpigmentation and sun damage
      throughout the entire body. Fractional photothermolysis also represents a
      particularly useful modality for difficult-to-treat conditions, such as melasma
      and acne scarring.

PMID- 17544940
TI  - Review of non-FDA-approved fillers.
AB  - The number of commercially available injectable soft tissue fillers has increased
      dramatically worldwide over the past decade. In the United States, a variety of
      temporary non-collagen-based fillers have been approved. However, no permanent
      soft tissue injectable fillers are currently approved by the US Food and Drug
      Administration. This article discusses some of the more popular soft tissue
      fillers, such as Restylane Fine Line, Restylane SQ, Perlane, Artecoll, Dermalive,
      Dermadeep, Bioalcamid, Bioplastique, Evolution, Outline, Argiform, and Aquamid,
      which are all available outside of the United States.

PMID- 17544941
TI  - Sailing the straits of approval: the nature of FDA approval and its implications
      for surgeons.
AB  - Use of Food and Drug Administration-approved medications and products for other
      than the approved indications is common in facial plastic surgery and violates no
      laws. Addressing practical concerns about such use strengthens the doctor-patient
      relationship and can minimize the risk of successful allegations of negligence in
      the event of untoward outcomes. The facial plastic surgeon can find support and
      assistance with off-label use in two general areas. Abundant scientific
      literature focuses on off-label use and addresses its practical, scientific,
      legal, moral, and ethical issues. The Food and Drug Administration also addresses
      off-label use in its own publications. It offers guidelines for physicians that,
      if followed, facilitate incorporation of off-label use into practice with minimal
      risk and maximum potential for therapeutic success.

PMID- 17544942
TI  - Understanding physician responsibilities and limitations for drug and device off
      label use.
AB  - Facial plastic surgery, by its nature, is a field that constantly is seeking new
      and innovative ways of treating patients. This innovation often involves novel
      techniques and tools. The US Food and Drug Administration is charged with
      regulating drugs and medical devices to ensure that the public is treated in safe
      and effective ways. It does not, however, regulate the practice of medicine.
      Physicians are able to use drugs and devices off-label but are required to follow
      certain guidelines. This article describes the physician's legal responsibilities
      and limitations in off-label drug or device use.

PMID- 17544943
TI  - Comprehensive periorbital rejuvenation with resorbable endotine implants for
      trans-lid brow and midface elevation.
AB  - Periorbital rejuvenation can enhance a patient's appearance, with changes of only
      a few millimeters making a significant impact. Many patients undergoing
      blepharoplasty often have mild brow or midfacial changes for which they are
      unwilling to undergo additional concurrent forehead or midface procedures,
      however, because these procedures may be associated with an unacceptable
      postoperative recovery and may not provide adequate tissue fixation. This article
      describes limited incision procedures capable of providing excellent elevation
      and support to the brow and midface that can be incorporated easily into a
      comprehensive periorbital rejuvenation treatment plan using semi-permanent
      subperiosteal fixation devices.

PMID- 17544944
TI  - The delivery of aesthetic medicine: illegal or not?
AB  - The field of aesthetic facial surgery is dynamic and may be driven by new
      technology and market trends. It is important that we respond to these pressures
      as small business persons, but only in the context of our obligations to our
      state regulatory boards, the Hippocratic Oath, and our patients' best interests.
      Regulations with regard to the scope of practice of aesthetic medicine and the
      corporate practice of medicine have the greatest potential to affect facial
      plastic surgeons. This article provides basic information regarding these
      medicolegal issues and resources to examine physician compliance. There may be an
      opportunity for the American Academy of Facial Plastic and Reconstructive Surgery
      to provide its membership with basic guidelines for scope of practice and
      corporate practice of medicine in an effort to optimize patient care.

PMID- 17544945
TI  - Incidence of cystic fibrosis in five different states of Brazil as determined by
      screening of p.F508del, mutation at the CFTR gene in newborns and patients.
AB  - Cystic Fibrosis (CF) is one of the most common single-gene defects in European
      descent populations with an incidence of about 1 in every 2500 live births and
      carrier frequency of approximately 1 in 25. The most common mutation at the CF
      transmembrane conductance regulator (CFTR) gene is a deletion (p.F508del) of the
      phenylalanine codon 508; its frequency, however, is not the same throughout the
      world. The purpose of this paper is to document an application of a two-tier
      survey design in different states of Brazil, from which regional differences of
      the incidence of CF and frequency of CF-causing mutation(s) carriers can be for
      the first time estimated. We present data on genotype distributions in reference
      to p.F508del mutation in samples of newborns, adult controls and CF patients from
      five Brazilian states, in which a total of 2683 newborns born to Brazilian white
      parents and 500 African-Brazilians adult controls were screened, as well as 300
      CF patients (262 European descents and 38 African descents) were genotyped. Our
      results suggest that the CF-incidence in different parts of Brazil may differ by
      almost 20-fold. For the five different states as a whole, nearly 48% of the CF
      alleles carry the p.F508del mutation, which places the estimates of disease
      incidence and carrier frequencies for the Brazilian European descents as 1 in
      7576 live births and 2.3%, respectively. The implications for prevention of CF
      and other rare Mendelian diseases through such surveys of mutation screening are
      discussed.

PMID- 17544947
TI  - Hypothalamic hamartoma: basic mechanisms of intrinsic epileptogenesis.
AB  - The hypothalamic hamartoma (HH) is a rare developmental malformation commonly
      associated with gelastic seizures that are notoriously refractory to medical
      therapy. Recent evidence supports the intrinsic seizure propensity of HH. Despite
      increasing clinical recognition of this condition, the mechanisms of seizure
      genesis in HH tissue remain unclear. This review summarizes the histochemical and
      electrophysiological properties of HH neurons, and relates these findings to
      those characteristics identified in other types of epileptic tissue. Initial
      studies have revealed two distinct populations of neurons in surgically resected
      HH tissue. One group consisted of small gamma-aminobutyric acid (GABA)-expressing
      neurons that occurred principally in clusters and displayed spontaneous rhythmic
      firing. The second group was composed of large, quiescent, pyramidal-like neurons
      with more extensive dendritic and axonal arborization. We propose that the small,
      spontaneously firing GABAergic neurons send inhibitory projections to and drive
      the synchrony of large output neurons. These observations constitute the basis
      for future investigations aimed at elucidating the mechanisms of subcortical
      epileptogenesis.

PMID- 17544948
TI  - Epilepsy in hypothalamic hamartoma: clinical and EEG features.
AB  - Hypothalamic hamartoma (HH) is a congenital malformation of the hypothalamus that
      may be asymptomatic or manifest with precocious puberty or seizures. Gelastic
      seizures often begin early in life, even in the newborn period, being manifest by
      frequent attacks of inappropriate laughter resulting from seizure activity in the
      HH. The scalp electroencephalogram (EEG) is often normal in children with
      gelastic seizures, such that the diagnosis of epilepsy and the finding of a HH
      are often delayed. In a proportion of children with HH, there is an epileptic
      progression, in which complex partial seizures with frontal, temporal, and
      lateralized clinical features appear, usually with the appearance of focal
      slowing and epileptiform activity on the interictal EEG. Further progression may
      ensue with the appearance of tonic or atonic drop attacks, generalized tonic
      clonic seizures, and epileptic spasms; rarely, infantile spasms may be the
      presenting seizure type. With the appearance of generalized seizures, the
      interictal EEG shows bilaterally synchronous and generalized epileptiform
      activity, often in abundance. The mechanism of this evolution is incompletely
      understood but neocortical seizure propagation and secondary epileptogenesis are
      believed to be important. Paralleling the development of the focal and
      generalized electroclinical manifestations in children with HH is usually slowing
      of development and the appearance of behavioral problems. Fortunately, many of
      these neurologic manifestations can be arrested, or reversed, with effective
      surgical treatment directed at the HH.

PMID- 17544949
TI  - Cognitive and behavioral dysfunction in children with hypothalamic hamartoma and
      epilepsy.
AB  - Hypothalamic hamartoma (HH) syndrome comprises the clinical triad of epilepsy,
      developmental retardation, and central precocious puberty. A predominant opinion
      has been that the acquired cognitive and behavioral disorders observed in
      children with this syndrome are a direct effect of their seizure activity. A
      review of the recent literature suggests that this opinion needs to be revised
      because it is only partially supported by the data. The size of the HH and its
      anatomic attachment/location, in addition to the seizure history, appear to
      contribute to the cognitive and behavioral disturbances in children with HH.
      Small sample sizes and the inability to use standard neuropsychological testing
      scales in more severely affected HH patients complicate the study of causality.
      The present literature, however, suggests that multiple factors contribute to the
      cognitive and behavioral problems of these children.

PMID- 17544950
TI  - Gamma knife surgery for epilepsy related to hypothalamic hamartomas.
AB  - Numerous neurosurgical approaches are available for children presenting with
      hypothalamic hamartomas (HHs) associated with severe epilepsy. A concern
      regarding the impairment of short-term memory after resective surgery is
      promoting the exploration of less invasive alternatives like radiosurgery. Gamma
      knife radiosurgery (GKS) can lead to a real reversal of the epileptic
      encephalopathy. Three years after radiosurgery, 60% of the children have an
      excellent result with complete seizure cessation in 40% and rare nondisabling
      seizures in 20%, often in association with dramatic behavioral and cognitive
      improvement. No permanent neurologic complications have thus far been reported.
      Rare transient cases of poikilothermia have been observed. GKS is clearly the
      safer approach for these difficult patients. Young patients with severe epilepsy
      and neurocognitive comorbidity must be treated by using a curative approach as
      early as possible. Topological type (according to our original classification) is
      the major feature for selection of the best treatment strategy. Type I HH deeply
      embedded in the hypothalamus is treated safely and efficiently by GKS. Type II HH
      can be resected by either endoscopic or transcallosal approaches or treated by
      GKS depending on the parent's choice and severity of epilepsy. In small type III
      HH, GKS is the safer procedure because of the very close relationship to the
      fornix and mammillary bodies. Types V (rarely epileptic) and IV are frequently
      operable by disconnection. Very large type VI (or mixed type) with a large
      component above the floor of the third ventricle must be disconnected, and then
      the upper remnant is best treated by GKS using a staged technique. Overall, when
      the lesion is sufficiently small, GKS offers a rate of seizure control comparable
      to microsurgery but with much lower risk. The disadvantage of radiosurgery is its
      delayed action. Longer follow-up is mandatory for a reliable evaluation of the
      role of GKS.

PMID- 17544951
TI  - Treatment options for gelastic epilepsy due to hypothalamic hamartoma:
      interstitial radiosurgery.
AB  - Surgical treatment of hypothalamic hamartomas (HHs) as the underlying etiology of
      gelastic epilepsy is associated with a high risk of complications because of the
      close vicinity of adjacent structures such as the optic tracts and mammillary
      bodies. Treatment with interstitial radiosurgery uses stereotactically implanted
      (125)I seeds emitting gamma radiation from the center of the lesion, with a steep
      spatial gradient, over a period of about 3 weeks. This form of HH therapy offers
      particular advantages regarding the risk for major side effects. In a series of
      15 children and adolescents treated in Freiburg, Germany, 53% of patients
      achieved significant improvement in seizure frequency (Engel class I or II
      outcome). Transient side effects were related to the development of local edema,
      resulting in headache and mental slowing. A persistent weight gain was noted in 3
      patients, which was severe in 1 (20 kg). There were no other neurologic,
      neuropsychologic, or neuropsychiatric side effects, which compares favorably with
      most surgical series.

PMID- 17544952
TI  - Hypothalamic hamartoma treatment: surgical resection with the transcallosal
      approach.
AB  - Multiple treatment options are available for patients with hypothalamic hamartoma
      (HH) including the frontotemporal approaches, the anterior transcallosal
      transseptal interforniceal approach, the transventricular endoscopic approach,
      and stereotactic radiosurgery. Relatively large patient series of the
      transcallosal resection/disconnection from Royal Children's Hospital in Melbourne
      and the Barrow Neurological Institute in Phoenix, AZ, show, respectively, that
      52% to 54% are 100% seizure free, and 24% to 35% have >90% seizure reduction.
      However, there appears to be an 8% to 14% risk of persisting memory problems. The
      surgery should ideally be performed in the early years of childhood before
      secondary generalized epilepsy develops and developmental delay and behavioral
      problems are established. Radiosurgery may be a preferable option for higher
      functioning adolescent or adult patients with HH. The choice of treatment must be
      individualized depending on the age and clinical circumstances of the patient and
      the size and anatomic relationships of the hamartoma. The transcallosal resection
      of HH is an effective and safe treatment, but there is a small risk of short-term
      memory impairment. The endoscopic approach is an alternative to the transcallosal
      approach for smaller HH.

PMID- 17544953
TI  - Endoscopic resection of hypothalamic hamartoma for refractory epilepsy:
      preliminary report.
AB  - The intrahypothalamic subtype of hypothalamic hamartoma (HH) is usually
      associated with refractory epilepsy, cognitive impairment, and organic behavioral
      disturbance. It is often a devastating disorder for both patient and family. The
      gelastic (laughing) seizure is the hallmark seizure type. However, multiple other
      seizure types can often develop during the course of the disease, and are
      typically refractory to antiepilepsy drugs (AEDs). Previously it was uncertain if
      HH tissue was responsible for seizure genesis or whether resection of the HH
      would result in improvement of the seizures. Recently both of these questions
      have been answered in the affirmative. Surgical resection using a transcallosal,
      interforniceal approach has recently been shown to be efficacious and generally
      safe for the treatment of the refractory seizures. However, even more recently,
      we have been performing the majority of HH surgical resection by using an
      endoscopic technique with a transventricular approach. This article presents the
      details of the operative technique and discusses preliminary outcome data,
      particularly with comparison to the transcallosal technique. Using an endoscope
      holder with micromanipulator facilitates endoscopic resection. Linking the
      endoscope to a system of frameless stereotaxis is essential for successful
      resection. Forty-four patients age 8 months to 44 years have undergone endoscopic
      resection. The ideal candidate for endoscopic removal has a hamartoma completely
      or nearly completely involving one wall of the third ventricle and is 1 cm or
      less in greatest diameter. Because it is essential to be able to visualize the
      lesion within the third ventricle for resection, there must be at least 6 mm of
      space between the top of the lesion and the roof of the third ventricle. Patients
      with intractable epilepsy caused by HH can be rendered seizure free or show
      marked improvement in seizure frequency by surgical removal, surgical
      disconnection, or radiosurgical ablation of the lesion. Which of these options
      should be recommended for an individual patient is not yet clear. One of the
      options involves resection or disconnection of the HH with a transventricular
      endoscopic approach. In selected patients, endoscopic resection of HH is
      effective in the treatment of intractable epilepsy, with lower complication rates
      and shorter hospital stays than transcallosal resection.

PMID- 17544954
TI  - Cerebrovascular responses to altitude.
AB  - The regulation of cerebral blood flow (CBF) is a complex process that is altered
      significantly with altitude exposure. Acute exposure produces a marked increase
      in CBF, in proportion to the severity of the hypoxia and mitigated by
      hyperventilation-induced hypocapnia when CO(2) is uncontrolled. A number of
      mediators contribute to the hypoxia-induced cerebral vasodilation, including
      adenosine, potassium channels, substance P, prostaglandins, and NO. Upon
      acclimatization to altitude, CBF returns towards normal sea-level values in
      subsequent days and weeks, mediated by a progressive increase in PO2, first
      through hyperventilation followed by erythropoiesis. With long-term altitude
      exposure, a number of mechanisms play a role in regulating CBF, including acid
      base balance, hematological modifications, and angiogenesis. Finally, several
      cerebrovascular disorders are associated with altitude exposure. Existing gaps in
      our knowledge of CBF and altitude, and areas of future investigation include
      effects of longer exposures, intermittent hypoxia, and gender differences in the
      CBF responses to altitude.

PMID- 17544956
TI  - Normal subcutaneous fat, necrosis of adipocytes and classification of the
      panniculitides.
AB  - The panniculitides represent a group of heterogeneous inflammatory diseases that
      involve the subcutaneous fat. The specific diagnosis of these diseases requires
      histopathologic study because different panniculitides usually show the same
      clinical appearance, which consists of erythematous nodules on the lower
      extremities. However, the histopathologic study of panniculitis is difficult
      because of an inadequate clinicopathologic correlation and the changing evolutive
      nature of the lesions. In addition, large scalpel incisional biopsies are
      required. From histopathologic point of view, all panniculitides are somewhat
      mixed because the inflammatory infiltrate involves both the septa and lobules.
      However, nearly always the differential diagnosis between a mostly septal and a
      mostly lobular panniculitis is straightforward at scanning magnification on the
      basis of the structures more intensely involved by the inflammatory infiltrate.
      Mostly septal panniculitides with vasculitis are actually more vasculitis than
      panniculitis and include superficial thrombophlebitis and cutaneous polyarteritis
      nodosa. Mostly septal panniculitides with no vasculitis include erythema nodosum,
      necrobiosis lipoidica, deep morphea, subcutaneous granuloma annulare, rheumatoid
      nodule, and necrobiotic xanthogranuloma. Mostly lobular panniculitis with
      vasculitis is only represented by erythema induratum of Bazin. In contrast,
      mostly lobular panniculitides without vasculitis comprise a large series of
      disparate disorders, including sclerosing panniculitis, calciphylaxis, sclerema
      neonatorum, subcutaneous fat necrosis of the newborn, poststeroid panniculitis,
      lupus erythematosus profundus, pancreatic panniculitis, alpha(1)-antitrypsin
      deficiency panniculitis, subcutaneous Sweet syndrome, infective panniculitis,
      factitial panniculitis, lipodystrophy, traumatic panniculitis, subcutaneous
      sarcoidosis, and sclerosing postirradiation panniculitis. Finally, some cutaneous
      lymphomas may simulate panniculitis, both from clinical and histopathologic
      points of view and, for that reason, they will be included in this review,
      although they are not inflammatory processes, but authentic lymphocytic neoplasms
      involving subcutaneous tissue.

PMID- 17544957
TI  - Superficial thrombophlebitis.
AB  - Superficial thrombophlebitis (STP) is a common disease usually characterized by
      an auto-resolving vasculitis of medium-sized veins of the upper subcutis or deep
      dermis that clinically manifests as a tender or painful palpable cord-like
      structure. It usually occurs in the setting of varicous veins, or hypercoagulable
      states, and may be the alarm signal for an underlining silent cancer. STP mainly
      involves the legs, but special locations, including the anterior chest wall or
      the penis, characterize specific clinical forms (Mondor's disease). The clinical
      signs and symptoms usually allow an easy diagnosis, but complementary techniques
      and biopsy are sometimes required. The main histopathologic differential
      diagnosis of STP is cutaneous polyarteritis nodosa.

PMID- 17544958
TI  - Cutaneous polyarteritis nodosa.
AB  - The term polyarteritis nodosa (PAN) presently includes classic systemic PAN,
      cutaneous PAN, and microscopic PAN (microscopic polyangeiitis). Cutaneous PAN
      involves the deep dermis and the panniculus, with anatomopathological findings
      diagnostic for arteritis. The most frequent clinical manifestation of cutaneous
      PAN is the presence of nodules on the lower legs, which frequently are found at
      different stages of development. At times, they may not leave residual changes,
      but generally a violaceous livedoid color or pigmentation with retiform
      appearance persists for months and even years. Ulceration also is a frequent
      complication of cutaneous PAN. Pain, arthralgias, malaise, and moderate fever are
      frequently associated symptoms. Histopathologically, cutaneous PAN shows a single
      artery involved with diagnostic inflammatory changes. The involved artery is
      always located in the deep dermis or in the panniculus. Inflammatory active skin
      nodules show a necrotizing arteritis with variable amounts of fibrinoid necrosis
      and leukocytoclasia, edema and inflammatory cells. The presence of focal
      panniculitis surrounding the involved artery is characteristic, in contrast with
      the more diffuse panniculitis usually found in other nodular diseases. Cutaneous
      PAN has a variable course, with repeated exacerbations. Salicilates relieve the
      pain in most instances and may be the only treatment required to improve the
      symptoms in patients with moderate flare-ups. A short course of corticosteroids
      therapy at a moderate dose is the most effective treatment to relieve the
      symptoms and to reduce the inflammation. Patients with an increased ASO titer
      should always be treated with penicillin.

PMID- 17544959
TI  - Necrobiosis lipoidica.
AB  - Necrobiosis lipoidica (NL) is a granulomatous condition with a degenerative
      connective tissue of unknown etiology very often associated with diabetes.
      Histopathologically, NL involves all of the dermis and, often, the subcutaneous
      fat produces a septal panniculitis. There are some changes suggesting the
      diagnosis of NL, and systemic disease should be considered if there is the
      presence of necrotizing vasculitis in the skin biopsy. Many theories of
      pathogenesis have been proposed, and many types of drugs are available for use in
      its treatment.

PMID- 17544960
TI  - Deep morphea.
AB  - Deep morphea encompasses a variety of clinical entities in which inflammation and
      sclerosis are found in the deep dermis, panniculus, fascia, or superficial
      muscle. Morphea profunda, eosinophilic fasciitis, and disabling pansclerotic
      morphea of children are included in this group, but overlapping of the extent and
      depth of cutaneous involvement in these various conditions precludes their
      distinction on the sole basis of clinical or even histologic examination.
      Furthermore, the limits between morphea profunda and generalized morphea, which
      usually are classified outside this group, are not clear. Histologically, all
      these disorders show similar inflammatory and sclerotic findings, the primary
      difference being the depth of these changes. Associated clinical findings,
      including arthralgias, arthritis, contractures, or carpal tunnel syndrome, are
      frequent. Although visceral complications are uncommon, pulmonary, esophageal,
      and even cardiac abnormalities have been reported. Eosinophilia,
      hypergammaglobulinemia, and increased erythrocyte sedimentation rate may be
      present with disease activity. Laboratory studies may demonstrate autoantibody
      production. Treatment is nonstandardized but UVA irradiation and antiinflammatory
      or immunosuppressive drugs (mainly antimalarial agents and corticosteroids) may
      be beneficial.

PMID- 17544961
TI  - Subcutaneous granuloma annulare.
AB  - Subcutaneous granuloma annulare is a rare clinicopathologic variant of granuloma
      annulare, characterized by subcutaneous nodules that may appear alone or in
      association with intradermal lesions. The pathogenesis of this deep variant of
      granuloma annulare remains uncertain. Subcutaneous granuloma annulare appears
      more frequently in children and young adults, and the lesions consist of
      subcutaneous nodules with no inflammatory appearance at the skin surface, most
      commonly located on the anterior aspects of the lower legs, hands, head, and
      buttocks. Usually, subcutaneous granuloma annulare is an authentic and exclusive
      panniculitic process with no dermal participation, although in 25% of the
      patients lesions of subcutaneous granuloma annulare coexist with the classic
      findings of granuloma annulare in the dermis. Histopathologically, subcutaneous
      granuloma annulare consist of areas of basophilic degeneration of collagen
      bundles with peripheral palisading granulomas involving the connective tissue
      septa of the subcutis. Usually, the area of necrobiosis in subcutaneous granuloma
      annulare is larger than in the dermal counterpart. The central necrobiotic areas
      contain increased amounts of connective tissue mucin and nuclear dust from
      neutrophils between the degenerated collagen bundles. Eosinophils are more common
      in subcutaneous granuloma annulare than in the dermal counterpart. There are not
      descriptions of subcutaneous granuloma annulare showing a histopathologic pattern
      of the so-called incomplete or interstitial variant. Histopathologic differential
      diagnosis of subcutaneous granuloma annulare includes rheumatoid nodule,
      necrobiosis lipoidica and epithelioid sarcoma.

PMID- 17544962
TI  - Rheumatoid nodule.
AB  - Rheumatoid nodules are the most common extra-articular manifestation of
      rheumatoid arthritis. Dermatologist may be concerned with the diagnosis and
      management of rheumatoid nodules, although most patients will probably be under
      the care of a rheumatologist. This article focuses in clinical, pathogenic,
      diagnostic, and therapeutic aspects of rheumatoid nodules. Classic rheumatoid
      nodules commonly occur in genetically predisposed patients with severe,
      seropositive arthritis. However, they may appear in other clinical settings.
      Accelerated rheumatoid nodulosis, especially involving the hands, has been
      reported in patients receiving methotrexate, antitumor necrosis factor alpha
      biologic drugs or leflunomide therapy for rheumatoid arthritis. Rheumatoid
      nodulosis is characterized by multiple rheumatoid nodules, recurrent joint
      symptoms with minimal clinical or radiologic involvement, and a benign clinical
      course. Pseudorheumatoid nodules have been reported in healthy children. Although
      histologically almost indistinguishable from true rheumatoid nodules, some
      consider these lesions to be a form of deep granuloma annulare.

PMID- 17544963
TI  - Necrobiotic xanthogranuloma.
AB  - Necrobiotic xanthogranuloma (NXG) is an uncommon granulomatous disease involving
      the skin and extracutaneous tissues. In its typical clinical presentation, it
      consists of multiple indurate yellow-brownish plaques or nodules, usually located
      on the periorbital area. The lesions often are bilateral and symmetric and
      frequently show tendency to atrophy and ulceration. Most cases are asymptomatic,
      and oral mucosal erosions are sometimes present. Ophthalmologic complications are
      observed in many patients, and NXG may involve other extracutaneous sites.
      Paraproteinemia is closely associated with NXG, demonstrating a monoclonal
      gammapathy, and other hematologic or lymphoproliferative disorders also may
      appear in association with NXG. Large areas of degenerated collagen alternating
      with granulomatous inflammation, multinucleate giant cells, cholesterol clefts,
      and lymphoid follicles are the most outstanding histopathologic characteristics
      of NXG. The prognosis for NXG is good, but no curative treatment is available.
      Chemotherapy with alkylating agents is the most frequently administered
      treatment, but oral and intralesional corticosteroids, interferon alpha,
      plasmapheresis, surgical excision, and radiation therapy also have been used for
      treatment of this disorder, with variable results.

PMID- 17544964
TI  - Erythema nodosum.
AB  - Erythema nodosum is the most frequent clinicopathologic variant of panniculitis.
      The process is a cutaneous reaction that may be associated with a wide variety of
      disorders, including infections, sarcoidosis, rheumatologic diseases,
      inflammatory bowel diseases, medications, autoimmune disorders, pregnancy, and
      malignancies. Erythema nodosum typically manifest by the sudden onset of
      symmetrical, tender, erythematous, warm nodules and raised plaques usually
      located on the lower limbs. Often the lesions are bilaterally distributed. At
      first, the nodules show a bright red color, but within a few days they become
      livid red or purplish and, finally, they exhibit a yellow or greenish appearance,
      taking on the look of a deep bruise. Ulceration is never seen, and the nodules
      heal without atrophy or scarring. Histopathologically, erythema nodosum is the
      stereotypical example of a mostly septal panniculitis with no vasculitis. The
      septa of subcutaneous fat are always thickened and variously infiltrated by
      inflammatory cells that extend to the periseptal areas of the fat lobules. The
      composition of the inflammatory infiltrate in the septa varies with age of the
      lesion. In early lesions edema, hemorrhage, and neutrophils are responsible for
      the septal thickening, whereas fibrosis, periseptal granulation tissue,
      lymphocytes, and multinucleated giant cells are the main findings in late stage
      lesions of erythema nodosum. A histopathologic hallmark of erythema nodosum is
      the presence of the so-called Miescher's radial granulomas, which consist of
      small, well-defined nodular aggregations of small histiocytes arranged radially
      around a central cleft of variable shape. Treatment of erythema nodosum should be
      directed to the underlying associated condition, if identified. Usually, nodules
      of erythema nodosum regress spontaneously within a few weeks, and bed rest is
      often sufficient treatment. Aspirin, nonsteroidal antiinflammatory drugs, such as
      oxyphenbutazone, indomethacin or naproxen, and potassium iodide may be helpful
      drugs to enhance analgesia and resolution. Systemic corticosteroids are rarely
      indicated in erythema nodosum and before these drugs are administered an
      underlying infection should be ruled out.

PMID- 17544965
TI  - Erythema nodosum leprosum: reactional leprosy.
AB  - The different clinical forms of leprosy are mainly related to the variety of
      immunological responses to the infection. Thus, lepromatous leprosy occurs in
      patients with a poor cell-mediated immunity to Mycobacterium leprae, whereas
      tuberculoid leprosy is associated with a high resistance to leprosy bacillus.
      Intermediate forms, including borderline tuberculoid leprosy, borderline
      lepromatous leprosy, and borderline leprosy, are a continuous and unstable
      spectrum of the disease. Leprosy reactions are rare and not well-known states
      that interrupt the usual chronic course and clinical stability of patients with
      leprosy. They are expressions of immunological perturbations. Attending to the
      clinical and histopathological manifestations, leprosy reactions may be separated
      in 2 or 3 different variants: reverse reaction (type I), erythema nodosum
      leprosum (type II), erythema polymorphous (type II) and Lucio's phenomenon,
      mainly considered a type II reaction, but sometimes designated type III. Type I
      leprosy reaction, also named "upgrading reaction," occurs in borderline leprosy
      states and is associated with a shift toward the tuberculoid pole. Type II
      reaction usually occurs in lepromatous leprosy, and there are 3 different
      clinical variants, including erythema nudosum leprosum, erythema polymorphous
      like reaction, and Lucio's phenomenon.

PMID- 17544966
TI  - Identification of a peptide from alpha-gliadin resistant to digestive enzymes:
      implications for celiac disease.
AB  - Current knowledge indicates that both innate and adaptive immune responses are
      involved in Celiac disease (CD) driven by different gliadin peptides. By studying
      a representative recombinant alpha-gliadin form, a further 25-mer peptide
      resistant to gastric, pancreatic, and human intestinal brush-border membrane
      enzymes was detected. This peptide latter encompasses the sequence 31-43 known to
      elicit the innate immune response in CD. The resistance of 25-mer, as well as
      that of the already described 33-mer related to the CD adaptive immune response,
      was confirmed on a standard flour wheat sample representative of the most
      widespread European varieties.

PMID- 17544968
TI  - Epidemiology and natural history of NAFLD and NASH.
AB  - Understanding of the epidemiology and natural history of non-alcoholic fatty
      liver disease (NAFLD) has increased; it is the most common form of chronic liver
      disease in the Western world and increasing in importance in other parts of the
      world. Prevalence is expected to increase as obesity and diabetes epidemics
      evolve. The natural history of NAFLD depends on the histologic subtype. Those who
      have simple hepatic steatosis or nonspecific inflammation generally have a benign
      long-term prognosis, whereas non-alcoholic steatohepatitis (NASH) can progress to
      cirrhosis. NASH-related cirrhosis may have a similar prognosis as cirrhosis from
      other causes, leading to liver failure or hepatocellular carcinoma.

PMID- 17544969
TI  - Pathologic assessment of non-alcoholic fatty liver disease.
AB  - Non-alcoholic fatty liver disease (NAFLD) represents one of the most common forms
      of liver disease and is considered the hepatic manifestation of the metabolic
      syndrome. Within the NAFLD spectrum, simple steatosis is considered benign,
      whereas non-alcoholic steatohepatitis (NASH) may progress to cirrhosis. The
      distinction can be made only by liver biopsy. There is not complete agreement on
      criteria for diagnosis or the features used for grading and staging lesions. This
      article reviews some of the studies dealing with the histopathology of NAFLD,
      with attempts to develop a standardized pathologic scoring system for NASH.

PMID- 17544970
TI  - Role of liver biopsy and serum markers of liver fibrosis in non-alcoholic fatty
      liver disease.
AB  - Non-alcoholic fatty liver disease (NAFLD) is common and may progress to end-stage
      liver disease. Liver-related morbidity and mortality occur almost exclusively in
      patients whose disease progresses to advanced fibrosis and cirrhosis. Presence
      and severity of liver fibrosis seem the most important indicators of long-term
      prognosis. Clinical and biochemical variables may help select NAFLD patients in
      whom liver biopsy may provide the most prognostic information. Some serum markers
      of liver fibrosis and imaging techniques aimed at measuring liver stiffness are
      under investigation as tools to determine severity of liver fibrosis in patients
      who have NAFLD, but none of them yet can replace liver biopsy.

PMID- 17544971
TI  - Role of radiologic modalities in the management of non-alcoholic steatohepatitis.
AB  - During the last decade, the role of radiologic modalities in management of
      patients who have fatty liver disease has expanded. Ultrasonography has been used
      as a noninvasive alternative to biopsy for monitoring patients who have hepatic
      steatosis, but MRI is more appealing than ultrasonography to denote minor changes
      in hepatic fat content. Distinguishing patients who have non-alcoholic
      steatohepatitis from steatosis alone has become of clinical importance; however,
      the differences are not apparent with any radiologic modalities. Several
      modalities have been developed to noninvasively and accurately quantify hepatic
      fat content and diagnose steatohepatitis. In the future, radiologic modalities
      might be used to monitor the natural history of the disease or evaluate
      therapeutic interventions in patients who have non-alcoholic fatty liver disease.

PMID- 17544972
TI  - Pathogenesis of NASH: animal models.
AB  - The incidence of non-alcoholic steatohepatitis, a disorder linked to visceral
      adiposity, insulin resistance, dyslipidemia, and type 2 diabetes mellitus, is
      increasing with the rise in the prevalence of the metabolic syndrome. This review
      focuses on animal models of steatohepatitis currently used to study (1) the
      mechanisms regulating hepatic lipid, glucose, and cholesterol homeostasis and (2)
      inflammatory recruitment and fibrogenesis in the steatotic liver. The ultimate
      aim of this research is to gain insights into the role of hepatic lipid,
      inflammation, and fibrosis in human non-alcoholic fatty liver disease.

PMID- 17544973
TI  - Pathogenesis of non-alcoholic steatohepatitis: human data.
AB  - Non-alcoholic fatty liver disease (NAFLD) has moved rapidly to the forefront of
      clinical disease, with a prevalence of 30% in the adult United States population
      and a definite but yet uncertain rate of progression to cirrhosis and end-stage
      liver disease. This disease has an impact on all areas of clinical medicine, with
      increasing prevalence and adversity. It is essential to understand the
      pathophysiologic mechanisms involved in NAFLD, so that therapeutic strategies can
      be developed. Although fatty liver may be caused by other factors, this review
      concentrates on fatty liver associated with insulin resistance, sometimes
      referred to as the primary form.

PMID- 17544974
TI  - Metabolic syndrome and NASH.
AB  - Clinical and epidemiologic studies have associated non-alcoholic fatty liver with
      the metabolic syndrome, with insulin resistance as the pivotal pathogenic factor.
      Obesity, type 2 diabetes mellitus, dyslipidemia, and hypertension contribute to
      risk for liver disease and to disease progression. The presence of multiple
      metabolic abnormalities is associated with the severity of liver disease.
      Patients have a high risk for cardiovascular morbidity and mortality, mediated by
      early atherosclerosis. This evidence has precise therapeutic implications: only a
      behavioral approach to lifestyle correction will address all alterations
      characterizing the metabolic syndrome, including metabolic liver disease.

PMID- 17544975
TI  - Medical treatment of non-alcoholic steatohepatitis.
AB  - There is no proven medical treatment of non-alcoholic steatohepatitis (NASH).
      Most prior therapeutic trials have had methodologic limitations. Insulin
      sensitizers are the more promising therapeutic candidates among categories that
      include antioxidants, lipid-lowering agents, and antiobesity drugs. The future
      will see the evaluation of novel agents and a comprehensive treatment strategy
      that addresses the risk factors for the metabolic syndrome. This article reviews
      the current status of medical management options for NASH.

PMID- 17544976
TI  - Surgical treatment for obesity and its impact on non-alcoholic steatohepatitis.
AB  - Non-alcoholic steatohepatitis (NASH) in obese and severely obese populations is
      associated with the metabolic syndrome, with features of the syndrome predicting
      those who will have NASH rather than simple steatosis, a more benign form of non
      alcoholic fatty liver disease. Substantial weight loss is proving the most
      effective therapy for obesity-related conditions. Improvements have seen the
      development of less invasive procedures. There is growing evidence that
      laparoscopic adjustable gastric banding and roux-en-Y gastric bypass provide
      effective therapy.

PMID- 17544977
TI  - Non-alcoholic steatohepatitis in children.
AB  - Non-alcoholic steatohepatitis (NASH) is an important liver disease in children;
      it can cause cirrhosis in children. The disease mechanism involves hepatic
      insulin resistance with hyperinsulinemia and changes in certain adipocytokines
      and inflammatory mediators. The differential diagnosis of childhood NASH includes
      metabolic disorders, drug hepatotoxicity, and alcoholic hepatitis in adolescent
      patients. The histologic features in childhood NASH often differ from those in
      adults who have NASH. Treatment is gradual weight loss through changes in food
      intake patterns and increased levels of physical activity; the role of drug
      treatment of NASH in children is an area of ongoing research.

PMID- 17544978
TI  - Steatosis as a cofactor in other liver diseases: hepatitis C virus, alcohol,
      hemochromatosis, and others.
AB  - As obesity prevalence rises, there is evidence that fatty liver disease can act
      synergistically with other chronic liver diseases to aggravate parenchymal
      injury. This is characterized best in chronic hepatitis C, where steatosis is
      caused by viral and metabolic effects. There is evidence that steatosis and its
      metabolic abnormalities also exacerbate other diseases, such as alcoholic liver
      disease, hemochromatosis, and, possibly, drug-induced liver disease. The
      pathogenesis seems related to increased susceptibility of steatotic hepatocytes
      to apoptosis, enhanced oxidative injury, and altered hepatocytic regeneration.
      Data suggest that active management of obesity may improve liver injury and
      decrease the progression of fibrosis in patients who have other chronic liver
      diseases.

PMID- 17544979
TI  - Non-alcoholic steatohepatitis and cancer.
AB  - Hepatocellular carcinoma (HCC) is part of the natural history of non-alcoholic
      steatohepatitis (NASH). A significant proportion of people who have cryptogenic
      cirrhosis develop HCC. NASH-related cirrhosis carries a substantial risk for
      early HCC development. Diagnosis of HCC often is made at first referral; the
      tumor usually is large with multiple localizations. Patients who have obesity or
      diabetes are at risk for HCC and a variety of cancers. Given the epidemic of
      obesity and diabetes, the incidence of NASH-related HCC is expected to increase.
      In addition to developing new diagnostic tools and pharmacologic therapies,
      efforts should be directed at preventing non-alcoholic fatty liver disease.

PMID- 17544980
TI  - The role of genomics and proteomics: technologies in studying non-alcoholic fatty
      liver disease.
AB  - Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis
      (NASH) are examples of complex diseases accompanied by changes in the expression
      of thousands of genes and a plethora of proteins encoded by these genes. Before
      the era of high-throughput analysis, typical translational research initiatives,
      aimed at defining the molecular targets for complex diseases, were performed on
      gene-by-gene basis. Innovative technologies, such as expression microarrays, mass
      spectromety, and reverse proteomics, now allow investigators to reveal complex
      patterns of the expression of biologically active molecules. For this reason,
      high-throughput approaches may be well suited for studies designed to untangle
      the molecular basis of the chronic liver diseases such as NAFLD.

PMID- 17544981
TI  - Napin from Brassica juncea: thermodynamic and structural analysis of stability.
AB  - The napin from Brassica juncea, oriental mustard, is highly thermostable,
      proteolysis resistant and allergenic in nature. It consists of two subunits - one
      small (29 amino acid residues) and one large (86 amino acids residues) - held
      together by disulfide bonds. The thermal unfolding of napin has been followed by
      differential scanning calorimetry (DSC) and circular dichroism (CD) measurements.
      The thermal unfolding is characterized by a three state transition with T(M1) and
      T(M2) at 323.5 K and 335.8 K, respectively; DeltaC(P1) and DeltaC(P2) are 2.05
      kcal mol(-1) K(-1) and 1.40 kcal mol(-1) K(-1), respectively. In the temperature
      range 310-318 K, the molecule undergoes dimerisation. Isothermal equilibrium
      unfolding by guanidinium hydrochloride also follows a three state transition, N
      <_-_-> I <_-_-> U with DeltaG(1H2O) and DeltaG(2H2O) values of 5.2 kcal mol(-1)
      and 5.1 kcal mol(-1) at 300 K, respectively. Excess heat capacity values
      obtained, are similar to those obtained from DSC measurements. There is an
      increase in hydrodynamic radius from 20 A to 35.0 A due to unfolding by
      guanidinium hydrochloride. In silico alignment of sequences of napin has revealed
      that the internal repeats (40%) spanning residues 31 to 60 and 73 to 109 are
      conserved in all Brassica species. The internal repeats may contribute to the
      greater stability of napin. A thorough understanding of the structure and
      stability of these proteins is essential before they can be exploited for genetic
      improvements for nutrition.

PMID- 17544982
TI  - Plasmodium falciparum dUTPase: studies on protein stability and binding of
      deoxyuridine derivatives.
AB  - Deoxyuridine triphosphate nucleotidohydrolase (dUTPase), a ubiquitous enzyme
      preventing a deleterious incorporation of uracil into DNA, has been thought of as
      a novel target for anticancer and antiviral drug design. The interaction of
      Plasmodium falciparum dUTPase (PfdUTPase) with deoxyuridine derivatives (dU,
      dUMP, dUDP and dUpNHpp) has been studied thermodynamically by both isothermal
      titration and differential scanning calorimetry. ITC shows no cooperativity for
      the binding of these derivatives. Dependencies in the binding thermodynamic
      parameters (enthalpy, entropy and Gibbs energy changes) with the number of
      phosphate groups in the nucleotide are obtained, and from the heat capacity
      changes no significant conformational changes upon binding are inferred. DSC
      shows PfdUTPase trimer is very stable but denatures irreversibly, with a more
      complex denaturation profile than other homologous trimeric dUTPases. The
      presence of magnesium ions does not influence the denaturation profile, while the
      presence of deoxyuridine derivatives increases the stability. The increase
      depends upon nucleotide concentration and type, with dUDP having the greater
      effect.

PMID- 17544983
TI  - Biphasic change and disuse-mediated regression of canal network structure in
      cortical bone of growing rats.
AB  - The canal network in cortical bone is an indispensable basis of bone vascularity,
      and its structure changes according to bone growth. Using monochromatic
      synchrotron radiation microCT (SRmicroCT), we evaluated the structural change of
      the canal network in growing rat tibiae and the response of this network to
      disuse. Tibiae were harvested from both hindlimbs of 9- and 14-week-old male
      Wistar rats subjected to unilateral sciatic neurectomy (SN) at 6 weeks of age
      (W9, n=8; W14, n=8) and from intact hindlimbs of 6-week-old rats (W6, n=8).
      Images of distal diaphyseal segments were reconstructed by SRmicroCT with a voxel
      size of 5.83 mum and then translated into local mineral densities using a
      calibrated relation between linear absorption coefficients and the concentration
      of K(2)HPO(4) solution. The canal network was segmented by simple thresholding at
      a bone mineral density of 0.82 g.cm(-3) and its structural properties were
      determined. In intact hindlimbs, the canal network showed a biphasic change with
      growth, as represented by increases followed by decreases in canal volume
      fraction (Ca.vol.f), the density of canals running longitudinally (Ca.num.d), and
      the density of canal connections (Ca.con.d): Ca.vol.f=2.2, 3.1, and 1.8%,
      Ca.num.d=77, 98, and 70 mm(-2), and Ca.con.d=18, 41, and 21 mm(-3) in W6, W9, and
      W14, respectively. In SN hindlimbs, bone growth deceleration was accompanied by a
      16% smaller Ca.vol.f and a 22% smaller Ca.con.d in W9 and a 27% smaller Ca.vol.f,
      a 12% smaller Ca.num.d, and a 39% smaller Ca.con.d in W14 than those in intact
      hindlimbs. Furthermore, the canal branching structure became more treelike in SN
      hindlimbs. The effect of SN on the canal network appeared mainly in the
      periosteal sector of the anteriolateral cortex in W9 and spread throughout the
      cortex in W14. These findings will lead to a better understanding of
      microcirculation in cortical bone growth.

PMID- 17544984
TI  - Ileal angiolipoma presenting as acute hemorrhage.

PMID- 17544985
TI  - Small bowel obstruction caused by endometriosis.

PMID- 17544986
TI  - Intraperitoneal and retroperitoneal hemorrhage associated with coumadin-induced
      bleeding into a pancreatic pseudocyst.

PMID- 17544987
TI  - Gastric intramural pseudocyst presenting as a gastric submucosal lesion.

PMID- 17544988
TI  - Swallowed teeth.

PMID- 17544989
TI  - A case of oral ingestion of elemental mercury.

PMID- 17544990
TI  - A moveable feast.

PMID- 17544991
TI  - The malignant colon polyp: diagnosis and therapeutic recommendations.
AB  - This article discusses the proper handling of the malignant colon polyp, that is,
      polypoid lesions that appear endoscopically to represent adenomas and
      histologically reveal an invasive carcinoma component, from the time of endoscopy
      to the pathologic diagnosis. Prognostically important pathologic features and a
      paradigm to guide treatment decisions are presented.

PMID- 17544992
TI  - Management of steroid-dependent ulcerative colitis: immunomodulatory agents,
      biologics, or surgery?

PMID- 17544993
TI  - Recurrent Clostridium difficile infection: an immunodeficiency state?

PMID- 17544994
TI  - Have we defined best colonoscopic polypectomy practice in the United States?

PMID- 17544995
TI  - Prospective study of bacteremia and complications With EUS FNA of rectal and
      perirectal lesions.
AB  - BACKGROUND & AIMS: Recent studies showed that endoscopic ultrasound (EUS)-guided
      fine-needle aspiration (FNA) is a low-risk procedure for causing bacteremia and
      infectious complications when sampling solid lesions of the upper
      gastrointestinal (GI) tract. As a result, antibiotics are not recommended for
      prophylaxis against endocarditis. Our aim was to prospectively evaluate the risk
      of bacteremia and other infectious complications in patients undergoing EUS FNA
      of lower GI tract lesions. METHODS: Patients referred for EUS FNA of lower GI
      tract lesions were considered for enrollment. Patients were excluded if there was
      an indication for preprocedure antibiotic administration based on American
      Society for Gastrointestinal Endoscopy guidelines, had taken antibiotics within
      the prior 7 days, or if they had a cystic lesion. Blood cultures were obtained
      immediately before the procedure, after flexible sigmoidoscopy/radial EUS, and 15
      minutes after EUS FNA. RESULTS: One hundred patients underwent a total of 471
      FNAs (mean, 4.7 FNAs/patient; range, 1-10 FNAs/patient). Blood cultures were
      positive in 6 patients. Cultures from 4 patients (4.0%, 95% confidence interval,
      1.6%-9.8%) grew coagulase-negative Staphylococcus (n = 2), Peptostreptococcus
      stomatis (n = 1), or Moraxella (n = 1), which were considered contaminants. Two
      patients (2.0%, 95% confidence interval, 0.6%-7%) developed bacteremia:
      Bacteroides fragilis (n = 1) and Gemella morbillorum (n = 1). No signs or
      symptoms of infection developed in any patient. CONCLUSIONS: EUS FNA of solid
      lesions in the lower GI tract should be considered a low-risk procedure for
      infectious complications that does not warrant prophylactic administration of
      antibiotics for the prevention of bacterial endocarditis.

PMID- 17544996
TI  - Determinants of gastroesophageal reflux disease in adults with a history of
      childhood gastroesophageal reflux disease.
AB  - BACKGROUND & AIMS: We conducted a nested case-control study to examine the
      prevalence and risk factors for current gastroesophageal reflux disease (GERD)
      symptoms in young adults with a history of childhood GERD. METHODS: We identified
      a cohort of individuals diagnosed with GERD in childhood during 1995-1996, and
      controls without childhood GERD. Patients with neurodevelopmental disorders,
      tracheoesophageal anomalies, or cystic fibrosis were excluded. A computer
      assisted telephone interview was conducted during 2004-2005. We calculated the
      prevalence of GERD symptoms, and examined the potential determinants of symptoms
      in unadjusted and adjusted logistic regression analyses. RESULTS: A total of 113
      cases completed the questionnaires (participation rate, 70.6%). The mean age of
      participants was 18 years, and their mean age at the time of childhood GERD
      diagnosis was 10 years. At least weekly heartburn or regurgitation was reported
      in 52 (46%) participants, 94% of whom were taking proton pump inhibitors, H2RA,
      or antacids. On the other hand, 33 controls were identified (44% participation
      rate) in whom weekly heartburn or regurgitation was reported in 30%. GERD was
      significantly more frequent in females using oral contraceptive pills (76.5%) as
      compared with females not on oral contraceptive pills (47.9%), or males (33.3%)
      (P = .008). Weight, height, nonsteroidal anti-inflammatory drug use, race, family
      history of GERD, education level, employment status, tobacco smoking, alcohol, or
      coffee drinking were not associated significantly with adulthood GERD.
      CONCLUSIONS: Frequent GERD symptoms requiring antisecretory therapy are present
      in approximately half of young adults with a history of childhood GERD. The use
      of oral contraceptives is a risk factor for GERD symptoms in these individuals.

PMID- 17544997
TI  - Gastroesophageal reflux and related pathology in adults who were born with
      esophageal atresia: a long-term follow-up study.
AB  - BACKGROUND & AIMS: Esophageal atresia (EA) is the most common congenital anomaly
      of the esophagus. There are few long-term follow-up data on adults who had
      surgery for EA as infants. The primary aims were to evaluate the prevalence of
      esophageal symptoms and pathology and second to develop recommendations for
      follow-up. METHODS: This is a descriptive study of individuals attending a clinic
      in an adult tertiary referral hospital, established to provide care for adults
      who had surgery for EA as infants. Individuals aged 20 years or older were
      identified from an existing database and invited by telephone to attend the
      clinic. One hundred thirty-two patients attended the clinic from 2000-2003.
      Individuals were assessed by using a structured questionnaire. Endoscopy was
      performed in 62 patients because of symptoms. RESULTS: Reflux symptoms were
      reported by 83 (63%), including 25 (19%) with severe symptoms. Dysphagia was
      reported by 68 patients (52%). Of those who underwent endoscopy, reflux
      esophagitis was present in 36 patients (58%), Barrett's esophagus in 7 (11%), and
      strictures in 26 (42%) patients. One patient was diagnosed with esophageal
      squamous cell carcinoma. Men who were 35 years or older and individuals with
      severe reflux symptoms were at high risk of having severe esophagitis or
      Barrett's metaplasia. CONCLUSIONS: Reflux symptoms, esophagitis, and Barrett's
      esophagus are common in these individuals. We recommend clinical assessment as
      adults and upper endoscopy for reflux symptoms or dysphagia. Transition of young
      adults from pediatric care to an adult gastroenterology clinic with expertise in
      EA appears to be highly beneficial.

PMID- 17544998
TI  - Association between IgG2 and IgG3 subclass responses to toxin A and recurrent
      Clostridium difficile-associated disease.
AB  - BACKGROUND & AIMS: Individuals who mount a significant serum immunoglobulin (Ig)G
      response to toxin A are protected against recurrent Clostridium difficile
      associated disease (CDAD). We investigated whether humoral immune deficiencies
      and/or specific IgG subclass responses are associated with recurrent CDAD.
      METHODS: We compared the clinical characteristics and humoral immune responses of
      13 patients with recurrent CDAD with 13 matched controls with a single CDAD
      episode. We measured the serum IgG titers to tetanus and diphtheria toxoids, as
      well as total and toxin A- and toxin B-specific serum IgG, IgA, and IgG subclass
      concentrations. RESULTS: There were no differences between the single and
      recurrent CDAD subjects in terms of age, sex, ethnicity, or other potential
      confounding variables. The total duration of diarrhea in patients with recurrent
      CDAD was greater (median, 62 vs 17 days; P = .005). IgG titers to tetanus and
      diphtheria toxoids, total IgG, and IgG subclass levels were similar in both
      groups. The total IgA was somewhat lower in those with recurrent CDAD (204 vs 254
      mg/dL; P = .05). IgA, IgG, IgG1, and IgG4 anti-toxin A and anti-toxin B levels
      were similar in both groups. However, IgG2 and IgG3 anti-toxin A levels were
      significantly lower in the recurrent group (P = .01 and .001, respectively).
      CONCLUSIONS: Subjects with recurrent CDAD did not show evidence of widespread
      humoral immune deficiency or of IgG subclass deficiency. Their low serum IgG anti
      toxin A concentrations reflected selectively reduced IgG2 and IgG3 subclass
      responses. Measurement of specific IgG2/3 anti-toxin A may be useful in selecting
      patients for treatment with agents to prevent recurrent CDAD.

PMID- 17544999
TI  - Environmental factors and colorectal tumor risk in individuals with hereditary
      nonpolyposis colorectal cancer.
AB  - BACKGROUND & AIMS: Individuals with hereditary nonpolyposis colorectal cancer
      (HNPCC) are at increased risk for colorectal cancer. Environmental factors might
      play a role in HNPCC-associated carcinogenesis. The aim of this study was to gain
      insight into the effects of environmental factors on colorectal tumor risk in
      individuals with HNPCC. METHODS: We examined associations between dietary
      factors, cigarette smoking, and HNPCC-associated colorectal tumors in a Dutch
      case-control study (145 cases, 103 tumor-free controls; all study participants
      were known or suspected carriers of a germline mutation in one of the DNA
      mismatch repair genes). We also assessed associations between the various
      environmental factors and occurrence of adenomatous polyposis coli (APC)
      mutations in HNPCC-associated polyps in a subset of the study population.
      RESULTS: Fruit consumption was inversely associated with ever developing HNPCC
      associated colorectal tumors (odds ratio [95% confidence interval] for highest vs
      lowest tertile, 0.4 [0.2-0.9]; P(trend) = .03); a borderline significant inverse
      association was observed for dietary fiber intake (0.5 [0.2-1.0]; P(trend) =
      .06). Cigarette smoking seemed to increase the risk of HNPCC-associated
      colorectal tumors. Truncating APC mutations were detected in 30 (37.5%) of the 80
      available HNPCC-associated polyps; frameshift mutations were most common (73.3%).
      None of the evaluated environmental factors was distinctively associated with a
      specific APC status of the polyps. CONCLUSIONS: Our data suggest that fruit
      consumption and dietary fiber intake might decrease the risk of colorectal tumors
      in individuals with HNPCC, whereas cigarette smoking might increase the risk of
      HNPCC-associated colorectal tumors. The observed associations support the
      hypothesis that HNPCC-associated outcomes might be modified by environmental
      factors.

PMID- 17545000
TI  - Factors associated with increased survival after photodynamic therapy for
      cholangiocarcinoma.
AB  - BACKGROUND & AIMS: Recent studies have shown a survival advantage using
      photodynamic therapy (PDT) in patients with unresectable cholangiocarcinoma.
      Factors associated with increased survival after PDT are unknown. METHODS: Twenty
      five patients with cholangiocarcinoma who were treated with PDT at the Mayo
      Clinic Rochester from 1991 to 2004 were studied. Porfimer sodium (2 mg/kg) was
      administered intravenously to patients with Bismuth type I (3 patients), type III
      a/b (13 patients), and type IV (9 patients) tumors. Forty-eight hours later, PDT
      was administered using a 1.5- to 2.5-cm diffusing fiber that was advanced across
      the tumor by either retrograde (20 patients) or percutaneous (5 patients)
      cholangiography. Laser light was applied for a total energy of 180 J/cm2 in 1-3
      applications. Patients received PDT treatments every 3 months. Plastic biliary
      stents (10-11.5 F) were inserted to decompress the biliary system after PDT.
      Survival analysis was performed using Kaplan-Meier curves and Cox proportional
      hazards models. RESULTS: Patients were 64 (standard error of the mean, +/-2.6)
      years of age; 20 (80%) were men. The median overall survival period was 344 days.
      The median survival period after PDT was 214 days. The 1-year survival rate was
      30%. On multivariate analysis, the presence of a visible mass on imaging studies
      (hazard ratio, 3.55; 95% confidence interval, 1.21-10.38), and increasing time
      between diagnosis and PDT (hazard ratio, 1.13; 95% confidence interval, 1.02
      1.25) predicted a poorer survival rate after PDT. A higher serum albumin level
      (hazard ratio, 0.16; 95% confidence interval, 0.04-0.59) predicted a lower
      mortality rate after PDT. CONCLUSIONS: Patients with unresectable
      cholangiocarcinoma without a visible mass may benefit from earlier treatment with
      PDT.

PMID- 17545001
TI  - Risk of lymphoma in primary biliary cirrhosis.
AB  - BACKGROUND & AIMS: A number of immunosuppressive therapies have not been
      associated with clinical benefit in primary biliary cirrhosis (PBC). The use of
      more potent immunomodulatory therapies, however, could raise concerns over the
      risk of adverse effects such as the development of lymphoma. Therefore, we sought
      to describe the frequency, clinical spectrum, and outcomes among patients with
      PBC and a concomitant diagnosis of lymphoma. METHODS: Patients with PBC evaluated
      at the Mayo Clinic between January 1, 1976-December 31, 1997 comprised the study
      cohort. Medical records were abstracted for demographic and clinical information
      including the temporal relationship between diagnoses and potential risk factors
      for lymphoma. RESULTS: From a total of 2192 patients, the frequency of lymphoma
      was observed at 0.6% (13 cases). The majority of patients (54%) had PBC before
      they were diagnosed with lymphoma, whereas 23% of cases were diagnosed in
      conjunction with PBC. Non-Hodgkin's lymphoma (69%) was observed in most cases
      with disease involvement above the diaphragm (38%). Treatment in the form of
      chemotherapy (n = 3), radiation (n = 2), and surgery (n = 6) was provided for 11
      patients. Seven (54%) patients did not have evidence for recurrent disease,
      whereas 3 (23%) patients died of progressive lymphoma. CONCLUSIONS: The baseline
      risk for lymphoma in patients with PBC is estimated at <1%. Clinical trials with
      potent immunosuppressive therapies for PBC should not be prohibited on the basis
      of concerns regarding a baseline predisposition for lymphoma in this population.

PMID- 17545002
TI  - Vascular rejection in heart transplantation: when ignorance is not bliss...

PMID- 17545004
TI  - Understanding the sensitized patient.
AB  - New technologies have resulted in the ability to identify the presence of IgG
      human leukocyte antigen (HLA) or non-HLA antibodies in the sera of potential
      solid organ transplant recipients. Knowledge of the presence of these antibodies,
      their antigen specificities, and strength (titer) is crucial to understanding a
      patient's state of immunologic sensitization and reactivity. Finally, these data,
      when correlated with sensitive crossmatch results, allow clinicians to make more
      knowledgeable clinical decisions when paring donors and recipients for
      transplant.

PMID- 17545005
TI  - Contemporary concepts in noncellular rejection.
AB  - Acute rejection is the major cause of morbidity and mortality in the first year
      after cardiac transplantation. Cellular rejection is the most common form of
      rejection observed; however, noncellular rejection is being seen more often. This
      noncellular rejection is mostly a result of less well-characterized antibody
      mediated mechanisms. Antibody-mediated rejection is associated more commonly with
      hemodynamic compromise, increased graft loss, cardiac allograft vasculopathy, and
      increased mortality. Histologic, immunofluorescence, and immunoperoxidase studies
      of endomyocardial biopsies from such patients often reveal intravascular
      macrophages and immunoglobulin and complement deposition in capillaries, in the
      absence of lymphoid infiltrates. Severely ill patients require intense therapy,
      which includes high-dose corticosteroids, cytolytic agents, intravenous heparin,
      intravenous gamma globulin, plasmapheresis, and/or antiproliferative agents.
      Further understanding of noncellular rejection will lead to more effective
      therapy.

PMID- 17545006
TI  - Tolerance in heart transplantation: the Holy Grail, or an attainable goal?
AB  - The father of cardiac transplantation, Norman Shumway, famously predicted that
      tolerance was the future of the field, and always would be. Although his
      prediction remains true to date, significant progress has been made toward this
      goal, the "Holy Grail" for transplant clinicians. Current efforts are fueled by
      disappointing long-term outcomes associated with chronic immunosuppression, and
      the promise that partial or complete tolerance will impact long-term results
      favorably. This article provides a clinical definition of tolerance primarily
      based on lessons learned from animal heart allograft models. It reviews several
      promising strategies for inducing tolerance and detecting its presence through
      the use of biomarkers in peripheral blood or the graft, and outlines a possible
      path toward making this vision a clinical reality.

PMID- 17545007
TI  - Induction therapy in cardiac transplantation: when and why?
AB  - Induction therapy has continued to be a subject of controversy in heart
      transplantation for more than 20 years. It is an example of a therapy that is
      logical, and ought to be better than "doing without." However, a careful review
      of the evidence suggests otherwise. Except for patients where the benefits
      clearly outweigh the short and long-term risks, the use of induction therapy
      should be avoided. In immunosuppression, as in life, there is no "free lunch."
      Clinicians need to be certain they fully understand what they are ordering when
      asking for induction therapy to be administered to their patients.

PMID- 17545008
TI  - Immunosuppression on the horizon.
AB  - Many novel immunosuppressive agents are under active clinical investigation. In
      addition, creative approaches are being developed for the use of established
      immunosuppressive agents, with the goal of minimizing immunosuppression as early
      as possible posttransplantation. The hope is that these approaches will minimize
      the toxicity of these agents without sacrificing efficacy. Evidence suggests that
      the nephrotoxicity of calcineurin inhibitors can be reduced using these
      approaches. The introduction of newer immunosuppressive agents, including the
      proliferation signal inhibitors, raises the possibility that some of the long
      term scourges of cardiac transplantation, including cardiac allograft
      vasculopathy and malignancy, can be ameliorated. Finally, costimulatory pathway
      inhibitors and other new immunosuppressive agents offer hope that all these goals
      can be accomplished with very low long-term maintenance immunosuppression.

PMID- 17545009
TI  - Echocardiography in the cardiac transplant recipient.
AB  - Despite the widespread use of echocardiography in the cardiac allograft
      recipient, the clinical usefulness of this practice is not well defined. In this
      article, the authors review the spectrum of echocardiographic findings in the
      adult heart transplant patient. Appreciation of typical alterations from "normal"
      allows the transplant physician to identify clinically significant changes and to
      avoid unnecessary invasive procedures based on misinterpretation of these
      differences. Though abnormalities of systolic and diastolic function correlate
      with episodes of acute rejection, the primary diagnostic usefulness of
      echocardiography in acute rejection is guiding the endomyocardial biopsy.
      Additionally, echocardiography has found a role as a supplement to invasive
      angiography in the diagnosis of cardiac allograft vasculopathy.

PMID- 17545010
TI  - Biomarkers after heart transplantation: nongenomic.
AB  - Patient monitoring following heart transplantation aims to detect complications
      (eg, acute graft rejection, vasculopathy, infection) early and contributes to
      risk prognostication. Numerous biomarkers of different biologic pathways have
      been evaluated as ancillary diagnostic and prognostic tools to reduce the need
      for invasive and expensive technical investigations. With the possible exception
      of cardiac troponins and N-type natriuretic peptides, no biomarkers have become
      established firmly in posttransplant patient surveillance. This article aims to
      show that the identification of a single biomarker that meets all needs
      (noninvasive diagnosis of rejection, prediction of transplant vasculopathy,
      survival prognostication) is unlikely. Rather, multiple marker strategies,
      including gene-based tests, are likely to enhance future monitoring quality and
      enable individualized risk-adapted patient management.

PMID- 17545011
TI  - Genomic biomarkers and heart transplantation.
AB  - Clinicians have entered into a new paradigm for managing heart transplant
      patients with use of multimarker gene expression profiling. Early after
      transplantation, when corticosteroid modification is the main concern, gene
      expression testing might assist in optimizing the balance of immunosuppression,
      defraying the occurrence of rejection, and avoiding crisis intervention. Late
      after transplantation, the reliance on endomyocardial biopsy could be lessened.
      These advances, if continually validated in practice, could usher in an era of
      decreased immunosuppression complications, lesser need for invasive surveillance,
      and more clinical confidence in immunosuppressive strategies.

PMID- 17545012
TI  - Cardiac allograft vasculopathy: an update.
AB  - Allograft vasculopathy remains the nemesis of long-term survival in heart
      transplantation. Possible modifying risk factors such as obesity, diabetes, and
      hypertension should continue to be pursued aggressively. All patients should
      receive statins. Clinical trials will provide the evidence needed to ascertain
      whether mammalian target of rapamycin inhibitors should be used in de novo
      cardiac transplant recipients to attenuate cardiac allograft vasculopathy (CAV).
      Intravascular ultrasound appears to play a key role in the diagnosis and
      evaluation of new treatments, and may indeed represent a surrogate marker that
      can be used to tailor management and improve outcomes. A better understanding of
      CAV is needed to develop targeted preventive therapies. Ongoing research in
      native atherosclerosis and vascular biology may provide answers within the next
      decade.

PMID- 17545013
TI  - When is retransplantation a viable option?
AB  - As the number of recipients of heart transplantation grows over time and they
      survive longer, more are at risk for developing severe cardiac allograft
      vasculopathy and allograft dysfunction, which might lead to consideration for
      retransplantation. Clearly, outcomes following cardiac retransplantation are
      compromised, and with donor shortage, the selection of candidates must be
      judicious. Retransplantation appears most appropriate for those patients more
      than 6 months following original heart transplantation, who have severe cardiac
      allograft vasculopathy and associated left ventricular dysfunction, or allograft
      dysfunction and progressive symptoms of heart failure in the absence of acute
      rejection. Relative contraindications to transplantation (ie, advanced age,
      comorbidities, psychosocial issues) require thorough assessment when
      retransplantation is being considered.

PMID- 17545014
TI  - [Preliminary study of PRL-3 gene promoter binding sites of Snail in SW480 cells].
AB  - OBJECTIVE: To identify the region in PRL-3 gene promoter where the
      transcriptional factor Snail can bind. METHODS: PRL-3 promoter and the possible
      binding sites of the transcription factors were analyzed by bioinformatical
      methods. Chromatin immunoprecipitation and PCR were performed using the antibody
      specific for Snail to verify the binding of Snail to PRL-3 promoter. RESULTS:
      According to the prediction by TRED, a promoter prediction software, PRL-3 gene
      promoter was located between -700 bp to 299 bp of PRL-3 gene. Many possible
      transcription factor binding sites such as for Snail, n-MYC, ARNT, E74A, NF
      kappaB, NRF-2 and AML-1 were predicted by Consite, a promoter analysis web
      system. Interestingly, a 5'-CACCTG-3' core sequence and other related sequences
      of Snail binding sites were found in the promoter region of PRL-3 genes by
      Consite software. Two regions in PRL-3 promoter were validated to allow binding
      of Snail by chromatin immunoprecipitation analysis of SW480 cells. CONCLUSIONS:
      Snail regulates the activity of PRL-3 gene by binding to the promoter of PRL-3
      gene in SW480 cells.

PMID- 17545015
TI  - [SDS-PAGE analysis of the antibacterial activity of the hemolymph from housefly
      larva].
AB  - OBJECTIVE: To study the inducible antibacterial activity of the hemolymph from
      housefly larva and analyze the antibacterial molecules. METHODS: The hemolymph
      was collected from the third instar housefly larvae 48 h after pricking
      treatment. Nine standard bacterial strains were used for determination of the
      antibaterial activity of the collected hemolymph and its combination with
      ampicillin. The anti-yeast activity of the hemolymph and its mixture with
      fluconazol was also assayed. The antibacterial molecules in the hemolymph was
      analyzed by SDS-PAGE. RESULTS: The growth of E.coli, Staphylococcus aureus,
      Staphylococcus albus, subserotypes of Shigeila flexneri, Bacillus proteus,
      Bacillus subtilis, Bacillus typhi, Bacillus paratyphosus, and Micrococcus
      lysodeikticus could be inhibited by the hemolymph collected from housefly larva,
      and the effect differed significantly between the groups (Plt;0.001). The
      hemolymph produced the strongest antibacterial activity against Micrococcus
      lysodeikticus, and the combination of the hemolymph with ampicillin most
      conspicuously inhibited the growth of Staphylococcus albus. The hemolyph and
      fluconazol exhibited obvious synergistic effect against yeast. SDS-PAGE
      identified some specific antibacterial molecules in the hemolymph. CONCLUSION:
      The induced hemolymph from housefly larva possesses strong antibacterial and
      antifungal activities especially against Micrococcus lysodeikticus. The hemolymph
      in combination with ampicillin produces the strongest effect against
      Staphylococcus albus, and fluconazol can significantly enhance the anti-yeast
      activity of the hemolymph through a synergistic mechanism.

PMID- 17545016
TI  - [Alternatively activated macrophages/mononuclear phagocytes promote growth and
      invasion of breast cancer cell line SKBR3].
AB  - OBJECTIVE: To study the effect of alternatively activated macrophages
      /mononuclear phagocytes(MNP) on breast cancer cells and explore the mechanisms
      for the action of tumor-associated macrophages in breast cancer. METHODS: Human
      peripheral blood monocytes were isolated and cultured in vitro and divided into 3
      groups, namely classically activated monocytes (CAM) which were induced by
      lipopolysaccharide, alternatively activated monocytes (AAM) induce by IL-4, and
      control cells treated with the culture medium only. After cell culture for 48-72
      h, the mRNA of tumor necrosis factor-alpha (TNF-alpha), alternative monocytes
      activation- associated CC-chemokine 1 (AMAC-1), and beta-actin of the 3 groups
      were extracted for RT-PCR, or the cells were cocultured with breast cancer cell
      line SKBR3, or seeded in chicken chorioallantoic membrane along with SKBR3.
      RESULTS: TNF-alpha mRNA was significantly increased in CAM, and AMAC-1 was highly
      expressed in AAM. The coculture experiments showed that CAM exhibited obvious
      inhibitory effect on SKBR3 cells after a 3-day culture whereas AAM significantly
      promoted the growth of SKBR3 cells after a 5-day culture. In chicken on
      chorioallantoic membrane experiment, the macrophages promoted tumor angiogenesis
      and AAM showed the most obvious effect. CONCLUSION: IL-4 induces high expression
      of AMAC-1, a molecular marker of AAM, in the macrophages, and AAM can promote the
      growth of SKBR3 cells and tumor angiogenesis.

PMID- 17545017
TI  - [Butenolide induces apoptosis of cultured chondrocytes: study of its mechanism].
AB  - OBJECTIVE: To observe cell apoptosis and Bcl-2 and Bax expression changes of
      chondrocytes induced by butenolide (BUT) and the inhibitory effect of selenium
      against BUT-induced chondrcyte apoptosis, to gain insights into the mechanism by
      which BUT induces chondrcyte apoptosis. METHODS: Cartilage tissue reestablished
      from human fetal articular chondrocytes in vitro were treated with BUT at the
      concentrations of 0.1, 1.0 and 5.0 microg/ml and with the protective factor
      selenium. TUNEL method was used to detect chondrocyte apoptosis, which was
      quantified by flow cytometry. Immunohitochemistry was performed to analyze the
      expression of Bcl-2 and Bax in the reestablished cartilage tissue. RESULTS: BUT
      exposure induced chondrocyte apoptosis, and the apoptosis rate increased with the
      concentration increment of BUT from 0 to 1.0 mg/ml, resulting also increased
      positive expression rate of Bcl-2 and Bax(P<0.05). The apoptosis rate of
      chondrocytes in BUT+ selenium group was significantly lower than that of BUT
      groups (P<0.05), as was the positivity rate of Bcl-2 and Bax expression (P<0.05).
      CONCLUSION: BUT induces chondrocyte apoptosis in positive relation with BUT
      concentration (from 0 to 1.0 mg/ml) and causes increased expressions of Bcl-2 and
      Bax. Selenium can inhibit the chondrocyte apoptosis induced by BUT.

PMID- 17545018
TI  - [Expression of CCL20 and CXCR4 in epidermal condyloma acuminatum lesions].
AB  - OBJECTIVE: To detect CCL20 and CXCR4 expressions in epidermis infected with
      condyloma acuminatum (CA) and normal epidermis and investigate the effect of
      their expressions on Langerhans cells in CA epidermis. METHODS: Gene expression
      of CCL20 and CXCR4 in 3 epidermal CA lesions and in 3 normal epidermis specimens
      were detected using Affymetrix oligonucleotide microarrays HG-U 133A 2.0, and the
      protein levels of CCL20 and CXCR4 in these specimens were measured by Western
      blotting. RESULTS: Microarray analysis revealed markedly down-regulated mRNA
      expressions of CCL20 and CXCR4 in the 3 epidermal CA lesions as compared with
      those in the normal specimens. Western blot analysis showed that the protein
      expressions of CCL20 and CXCR4 in the CA lesions were significantly lower than
      those in normal epidermis. CONCLUSION: The protein and mRNA expressions of CCL20
      and CXCR4 are markedly down-regulated in epidermal CA lesions, which may
      contribute to decreased number and backflow disturbance of Langerhans cells in
      these lesions.

PMID- 17545019
TI  - [Localization of cracking sounds caused by cervical rotatory and local
      manipulation].
AB  - OBJECTIVE: To localize the facet joints that give rise to the cracking sounds
      caused by cervical rotatory and local manipulation. METHODS: Cervical rotatory
      and local manipulation was performed in 30 healthy adults at the spinous process
      at the C(4 )level once on each of the left and right side, and a set of equipment
      we designed for acoustic signal acquisition was applied to collect and locate the
      cracking sounds, followed by statistical analysis of the data collected. RESULTS:
      The cracking sounds caused by cervical rotatory and local manipulation were
      localized mainly at C(3-7) facet joints, and the times of cracking sounds at
      these facet joints had significant differences from those at the other facet
      joints. CONCLUSION: The location of cervical rotatory and local manipulation can
      be only relative, and definite localization seems impossible.

PMID- 17545020
TI  - [Nitroglycerine promotes myocardial oxygen metabolism and regional cardiac
      function in vivo].
AB  - OBJECTIVE: To investigate the effects of nitroglycerine (NTG) on myocardial
      oxygen metabolism and regional cardiac function in canine hearts with a stable
      systemic hemodynamics in situ. METHODS: Eight anesthetized open-chest dogs with
      flow-limited left anterior descending branch of the coronary artery or left
      circumflex artery (LCx) stenosis were studied. The percentage of ventricular wall
      thickening (%WT) was measured with quantitative two-dimensional echocardiography
      (2DE), myocardial blood flow (MBF) with radiolabeled microspheres and tissue
      oxygen pressure (tPO(2).) with oxygen-dependent quenching of phosphorescence. 2DE
      was performed and radiolabeled microspheres and Pd-porphyrin injected in the dogs
      at rest during intracoronary infusion of 0.3-0.6 mg x kg(-1) x min(-1) of NTG.
      Myocardial oxygen consumption (MVO(2), ml x min(-1) x 100 g(-1)) was calculated
      as the multiplication product between the arterio-venous oxygen content
      difference and MBF, and myocardial O(2) delivery as the product between arterial
      oxygen content and MBF. RESULTS: As compared with the baseline, NTG increased %WT
      and MBF significantly in both normal and ischemic beds (P<0.05). There was a
      significant increase in MVO(2) during NTG infusion in the ischemic bed (P<0.05)
      in comparison with that measured at rest. NTG, however, significantly increased
      the ability of myocardial O(2) delivery in both normal and ischemic beds
      (P<0.05), therefore tPO(2) was still higher in the ischemic bed during NTG
      infusion than that at rest (P<0.05). The percentage increment in tPO(2) was
      significantly greater in the ischemic bed than percentage MBF increment.
      CONCLUSIONS: NTG enhances myocardial oxygen concentration in normal and ischemic
      myocardium and may increase oxygen release to the ischemic myocardium in vivo.
      NTG may have a positive inotropic effect on regional cardiac function. In
      addition to direct effect on vascular tone, NTG plays important roles in the
      cardiovascular system by modulating myocardial oxygen metabolism and contractile
      function.

PMID- 17545021
TI  - [Comparative proteomic analysis of the prefrontal cortex between normal and
      heroin-addicted rats].
AB  - OBJECTIVE: To obtain two-dimensional gel electrophoresis maps of the prefrontal
      cortex (PFC) proteins of normal and heroin-addicted rats for identifying the
      differentially expressed proteins in the addicted rats. METHODS: Rat models of
      heroin addiction were established, and the proteins in the PFC underwent two
      dimensional gel electrophoresis with immobiline pH gradient isoelectric focusing
      as the first and vertical SDS-PAGE as the second dimension. ImageMaster 2D 5.0
      analysis software, matrix assisted laser desorption/ionization-time of flight
      mass spectrometry (MALDI-TOF-MS) or MALDI-TOF-TOF-MS as well as NCBInr database
      searching were performed to separate and identify the proteome in the rat PFC.
      RESULTS: Seven protein spots to represent 5 proteins were identified by PMF and
      MALDI-TOF-TOF-MS. Among those proteins, glucose-regulated protein (58 kD) and 26
      S proteasome subunit p40.5 existed only in heroin-addicted rats, in which ATP
      synthase D chain was down-regulated. Ndufa10 and Eno1 were present in both
      groups, but their molecular mass and pI were different. CONCLUSION: Immobilized
      pH gradient two-dimensional gel electrophoresis allows good reproducibility in
      separation and identification of the proteome in the PDF of heroin-addicted rats,
      which facilitates further investigation of pathogenic mechanisms of heroin
      addiction and central nerve injury.

PMID- 17545022
TI  - [Complementarity-determining region 3 analysis of T cell receptor beta chain
      variable region in peripheral blood mononuclear cells cultured with interleukin
      2].
AB  - OBJECTIVE: To analyze the drift of the complementarity-determining region 3
      (CDR3) of T cell receptor beta (TCRbeta) chain variable region in T cells of
      healthy volunteers cultured with interleukin-2 (IL-2). METHODS: T cells were
      isolated from the peripheral blood and cultured in vitro in the presence of IL-2.
      The non-specific killing effect of the cells was analyzed by LDH releasing assay,
      and the distribution of TCRbeta chain CDR3 in healthy volunteers by immunoscope
      spectratyping method to evaluate the clonality of the T cells. RESULTS: The
      results showed Gaussian distribution of TCR Vbeta gene CDR3 in healthy
      volunteers. The T cell cultured with IL-2, however, displayed some anomalous and
      oligoclonal expansion in different TCR Vbeta families without killing effect
      against nasophargngal carcinoma cell line CNE2. CONCLUSION: IL-2 may affect
      TCRbeta chain CDR3 distribution in T cells cultured in vitro.

PMID- 17545023
TI  - [Association between environmental risk factor exposure in the first trimester
      and nonsyndromic cleft lip with or without cleft palate: a case-control study].
AB  - OBJECTIVE: To identify the environmental risk factors during the first trimester
      responsible for nonsyndromic cleft lip with or without cleft palate to collect
      data for prevention of this congenital defect. METHODS: A hospital-based case
      control study was conducted to identify the risk factors by means of field
      investigation with standardized questionnaires. Single factor analysis and
      logistic regression of the data are performed using SPSS 13.0 software. RESULTS:
      Multifactorial analysis revealed that folic acid was significantly associated
      with lowered incidence of nonsyndromic cleft lip with or without cleft palate
      (OR=0.100, 95%CI: 0.032-0.312), whereas maternal infection (OR=4.155, 95%CI:
      2.166-7.970), poisonous chemical exposure (OR=6.816, 95%CI: 2.528-18.381) and
      emotional stress (OR=3.250, 95%CI: 1.477-7.154) were risk factors for this
      defect. CONCLUSIONS: Sufficient follic acid intake and prevention of infection
      and poisonous chemical exposure during the first trimester are measures to reduce
      the risks of nonsyndromic cleft lip with or without cleft palate.

PMID- 17545024
TI  - [Neonatal outcomes of pregnancy resulting from in vitro fertilization and embryo
      transfer: analysis of 1274 cases].
AB  - OBJECTIVE: To evaluate the neonatal outcomes of pregnancies resulting from in
      vitro fertilization and embryo transfer (IVF-ET) in relation to the occurrence of
      congenital malformations of the neonates. METHODS: A total of 1274 infants born
      after IVF-ET were reviewed. The neonatal outcome was evaluated based on
      gestational weeks, body weight, congenital malformations, manner of
      spermatization, maternal age and multiple gestation. RESULTS: IVF-ET resulted in
      930 deliveries, giving birth to a total of 1274 newborns. Spontaneous delivery
      occurred in 115 cases (12.37%), with preterm birth in 224 cases (24.09%). Among
      these newborns, 363 (28.49%) had very low born weight (VLBW), 13 (1.02%) had
      congenital malformations, and neonatal mortality occurred in 15 cases (1.18%).
      CONCLUSION: IVF increases the risks of twin pregnancies, preterm birth and VLBW,
      but does not increase the rate of congenital malformations and neonatal
      mortality. Intracytoplasmic sperm injection (ICSI) is at higher risk of
      congenital malformations. Maternal age and twin pregnancies are not associated
      with congenital malformations. IVF can be safe for treatment of infertility.

PMID- 17545025
TI  - [Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry
      for proteomic analysis of seminal plasma in patients with delayed semen
      liquefaction].
AB  - OBJECTIVE: To identify the differentially expressed proteins in seminal plasma
      between subjects with normal fertility and those with delayed semen liquefaction
      by proteomic techniques. METHODS: Semen samples of 6 patients with delayed semen
      liquefaction and 11 subjects with normal fertility (control group) were
      collected. Seminal plasma were separated and examined with surface-enhanced laser
      desorption/ionization time of flight mass spectrometry to compare the protein
      expressions between the two groups. RESULTS: Compared with normal control group,
      19 proteins were differentially expressed in the patients including 6 proteins
      with significant differences between the two groups, with m/z of 8696.621,
      9770.076, 9512.309, 10202.64, 2941.903, and 9617.759, respectively (P<0.01).
      CONCLUSION: Screening of differentially expressed proteins in seminal plasma may
      help understand the mechanism of delayed semen liquefaction for its potential
      clinical intervention.

PMID- 17545026
TI  - [Construction and identification of adenovirus vector for double-mutant human
      hypoxia-inducible factor-1alpha gene].
AB  - OBJECTIVE: To construct an adenovirus vector containing the double-mutant hypoxia
      inducible factor-1alpha (HIF-1alpha) gene for exploring the therapeutic
      angiogenesis for coronary heart disease. METHODS: Human double-mutant HIF-1alpha
      cDNA was obtained from PCR of pShuttle-2-HIF-1alpha containing the mutant HIF
      1alpha gene (564). The recombinant adenoviral plasmid containing mutant HIF
      1alpha cDNA was constructed by ligation of recombinant pShuttle2 containing
      double-mutant HIF-1alpha cDNA and Adeno-X viral DNA, followed by its
      identification and transfection into adenoviral packaging cells HEK293 via
      lipofectamine 2000. RESULT AND CONCLUSION: The recombinant pAdeno-HIF-1alpha was
      correctly constructed and verified by restriction endonuclease and DNA sequencing
      analyseis. This recombinant adenovirus containing the double-mutant HIF-1alpha
      gene may facilitate further investigation of mutant HIF-1alphagene therapy for
      coronary heart disease.

PMID- 17545027
TI  - [Analysis of clinical manifestations of subheath status in a medical college of
      Guangdong Province].
AB  - OBJECTIVE: To explore the clinical manifestation of subhealth status in teachers
      and medical staff. METHODS: An on-the-spot investigation was conducted in 891
      personnel of a medical college using a self-designed subhealth questionnaire. The
      diagnostic criteria for subhealth status were formulated on the basis of
      literature review and expert counseling. The results were analyzed by frequency
      analysis and multiple-factor logistic analyses. RESULTS: The total subhealth
      incidence was 57.2 %, and the clinical manifestations included many symptoms of
      the body, psychology and society. Multiple-factor logistic analysis revealed the
      most common clinical manifestations of subhealth status including ademonia,
      weariness, insomnia, waist and back pain, frequent sighs, eye dryness,
      inattention, irritability, foot and hand coldness, vulnerability to common cold
      etc. CONCLUSION: The clinical manifestations of sub-health status complex.

PMID- 17545028
TI  - [Directional differentiation of murine CD117+ hemopoietic stem cells into
      immature dendritic cells and their identification].
AB  - OBJECTIVE: To establish a stable method for obtaining large quantity of highly
      purified immature dendritic cells (imDCs) in vitro, and identify the morphology,
      function and surface markers of the cells. METHODS: CD117(+) hemopoietic stem
      cells (HSCs) were isolated and purified from the bone marrow of healthy C57 mice
      by magnetic affinity cell sorting. After cell expansion by treatment with stem
      cell factor (SCF) and interleukin-3 (IL-3), the HSCs were induced for directional
      differentiation into imDCs by treatment with GM-CSF, IL-4 and IL-10. The imDCs
      obtained were identified by morphological and functional observation under
      inverted microscope, scanning electron microscope and transmission electron
      microscope, followed by detection of the expressions of the surface markers using
      flow cytometry. RESULTS: After 3, 5 and 7 days of culture in the presence of
      SCF+IL-3, the cells were expanded by 10.34-/+1.43, 22.65-/+2.71 and 54.39-/+3.08
      folds, respectively. The HSCs were successfully induced to differentiate into
      imDCs with phagocytotic activity. The dendrites of the imDCs were short small,
      and appearing spinous. The expressions of surface markers were detected from the
      cells showing the phenotype of CD11c(+), I-A/I-E(low), CD40(-), CD80(-), CD86(-).
      CONCLUSION: The method described allows steadily acquisition of large quanty of
      highly purified imDCs and of their effective identification in vitro.

PMID- 17545029
TI  - [Expression pattern of nitric oxide synthase in the retina of diabetic rats].
AB  - OBJECTIVE: To investigate the expression of nitric oxide synthase (NOS) in the
      retina of 8-week-old diabetic rats, and explore the potential molecular
      mechanisms for the role of NO in diabetic retinopathy (DR). METHODS: Retinal gene
      expression profile of normal and 8-week-old diabetic rats was constructed with
      restriction fragment differential display polymerase chain reaction (RFDD-PCR).
      Bioinformatic analysis of the differentially expressed gene identified the genes
      coding for 3 subtypes of NOS, namely eNOS, nNOS and iNOS as the candidate genes
      related to DR, which was verified using semi-quantitative RT-PCR and
      immunohistochemistry. RESULTS: The results of RFDD-PCR revealed down-regulated
      expression of eNOS and nNOS and up-regulated iNOS expression in diabetic rat
      retina. RT-PCR showed that the expression levels of eNOS and nNOS in diabetic rat
      retina were obviously lower than that in normal retina (0.23-/+0.03 vs 0.32
      /+0.03 for eNOS, P<0.05; 0.25-/+0.02 vs 0.36-/+0.02 for nNOS, P<0.05), but the
      expression level of iNOS obviously higher (0.27-/+0.02 vs 0.20-/+0.03, P<0.05).
      Immunohistochemistry of healthy retina visualized eNOS-, nNOS- and iNOS-positive
      cells, all located in the inner nuclear layer (INL) and ganglion cell layer
      (GCL), and eNOS-positive cells were also found in vascular endothelium. In
      diabetic retina, the number of eNOS- and nNOS-positive cells was significantly
      lowered in comparison with normal rat retina (14.33-/+3.19 vs 22.13-/+3.60 for
      eNOS, P<0.05; 21.87-/+3.62 vs 34.40-/+7.09 for nNOS, P<0.05), but the number of
      iNOS-positive cells significantly increased (17.60-/+2.58 vs 11.73-/+2.70,
      P<0.05). CONCLUSION: The alterations in eNOS, nNOS and iNOS expression are
      associated with the deuelopmant and progression of DR.

PMID- 17545030
TI  - [Clinical study of Osaka formula and improved multiparameter ultrasonic
      measurement for fetal weight estimation].
AB  - OBJECTIVE: To analyze the factors affecting the accuracy of Osaka formula
      multiparameter ultrasound-based fetal mass estimation, thereby establishing new
      formulas to improve the accuracy of the estimation. METHODS: A retrospective
      review was conducted among 519 healthy women with singleton pregnancy. Three days
      before the delivery (between 37 and 42 weeks' gestation), ultrasonic measurement
      of the fetal weight and other indices of the fetus was routinely performed.
      Correlation and multiple linear stepwise regression analysis were used to correct
      the 3 equations, which, along with Osaka University formula, were used to predict
      another 219 fetuses' birth weight. The coincidence rate of the predicted value
      and with the actual birth weight, and the absolute error and relative error were
      compared between the equations. RESULTS: The fetal abdominal area (AA) and
      abdominal circumference (AC) showed the most conspicuous influence on the
      estimated fetal birth weight, and fetal humerus length (HL) was more sensitive
      than femur length (FL) for the estimation. Three new regression equations were
      established, among which the equation 2 (fetal birth weight=1082.859+4.116xAAxHL)
      showed the best accuracy in clinical prediction. CONCLUSION: AA,AC and HL are
      more sensitive indices for estimation of the fetal birth weight, and the equation
      2 established in this study still awaits further verification for its clinical
      value.

PMID- 17545031
TI  - [Lethal effect of adenovirus-mediated HSV-TK gene in combination with
      hydroxycamptothecin on human bladder cancer in vitro].
AB  - OBJECTIVE: To evaluate the lethal effect of adenovirus-mediated HSV-TK
      ganciclovir (GCV) gene therapy in combination with hydroxycamptothecin (HCPT) on
      hunman bladder carcinoma cell line T-24 cells. METHODS: Human bladder carcinoma
      cell line T-24 was transfected with adenovirus expression vector containing TK
      gene and green fluorescent protein (GFP) gene, and the transfection efficiency
      was observed and TK expression detected by PCR. After successful cell
      transfection indicated by GFP expression, GCV and hydroxycamptothecin are
      respectively added into the cell culture with normal T-24 cells serving as the
      blank control group. The growth inhibition rate of hunman bladder carcinoma cells
      in response to HCPT treatment for 72 h and the cell survival rate of 24 h, 48 h
      and 72 h after transfection with different protocols were observed by MTT assay.
      The apoptosis of the cells treated with GCV (0.5 mg/ml)+HCPT (10 mg/L) for 4 h
      was observed by flow cytometry. RESULTS: The cell inhibition rate increased
      gradually with increment of HCPT concentration, from 14% at HCPT concentration of
      0.01 mg/L to 60% at 50 mg/L, but for a concentration above 100 mg/L, the
      inhibition rate did not exhibit further increase (P=0.216). GCV alone and GCV in
      combination with HCPT both resulted in significantly decreased survival rate of
      human bladder carcinoma cells (P=0.00), and the killing efficiency of the cells
      by GCV+HCPT protocol increased obviously with increment of HCPT concentration and
      prolongation of the action time. The cells treated with 0.5 mg/ml GCV alone for
      72 h retained a cell survival rate of 34.6%, which was lowered to only 8.07% with
      combined treatment with GCV (0.5mg/ml) and HCPT (10 mg/L). Typical apoptotic peak
      before M1 phase of the cells appeared 4 h after treatment with GCV+10 mg/ml HCPT,
      which resulted in a apoptosis rate of 52.93%. CONCLUSION: HSV-TK/GCV in
      combination with HCPT can enhance the lethal effect of suicide gene therapy
      against human bladder carcinoma cells and effectively induce apoptosis of the
      cells.

PMID- 17545032
TI  - [Specific small interfering RNAs inhibit replication of hepatitis B virus].
AB  - OBJECTIVE: To obtain specific small interfering RNAs (siRNA) for hepatitis B
      virus (HBV) and evaluate their interfering effect. METHODS: Three siRNAs were
      transfected into HepG2.2.15 cells, and the amount of HBV mRNA in the cell culture
      medium was quantified with real-time fluorescence quantitative RT-PCR. HBsAg in
      the culture media was assayed with Western blotting at different time points
      after transfection. RESULTS: The cells transfected with specific siRNAs showed
      decreased levels of HBV mRNA and HBsAg (P<0.05), but those with nonspecific siRNA
      transfection as the negative control did not show such changes (P>0.05).
      CONCLUSION: Specific siRNA can significantly inhibit protein expression and mRNA
      synthesis of HBV in HepG2.2.15 cells in vitro.

PMID- 17545033
TI  - [Induced differentiation of bone marrow stem cells in transplanted rat liver].
AB  - OBJECTIVE: To investigate the differentiation of bone marrow stem cells in
      transplanted livers and its impact on the long-term survival of rats with
      orthotopic liver transplantation. METHODS: Twenty-four female recipient rats with
      orthotopic liver transplantation were randomized into blank-control group, D
      hanks solution group, bone marrow stem cells group with postoperative infusion of
      stem cells, and the pathological changes of the liver grafts and survival time of
      the rats were observed. The differentiation of the bone marrow stem cells were
      assessed 60 days after transplantation using in situ hybridization histochemistry
      for Sry gene and alpha-fetoprotein (AFP) immunohistochemistry. RESULTS: In rats
      with postoperative infusion of bone marrow stem cells through the portal vein,
      the median long-term graft survival time exceeded 180 days, significantly longer
      than that in the other two groups (P<0.05), and no obvious evidence of acute
      rejection was observed with positive Sry expression and AFP expression.
      CONCLUSION: Infusion of bone marrow stem cells through the portal vein following
      liver transplantation may alleviate acute graft rejection and promote long-term
      liver graft survival and AFP expression.

PMID- 17545034
TI  - [Value of perioperative adjuvant therapy in liver transplantation for advanced
      hepatocellular carcinoma].
AB  - OBJECTIVE: To evaluate the clinical value of perioperative adjuvant chemotherapy
      in prevention of tumor recurrence and improvement of patient survival after liver
      transplantation for advanced hepatocellular carcinoma (HCC). METHODS: Twenty
      patients with advanced HCC (pTNM stages III and IV a) receiving liver
      transplantation with preoperative transcatheter arterial chemoembolization (TACE)
      and postoperative adjuvant chemotherapy (ADM+5-Fu+CDDP) were retrospectively
      reviewed in comparison with 16 patients receiving liver transplantation only for
      tumor recurrence, cumulative and tumor-free survivals. The feasibility and side
      effects of the treatments were also studied. RESULTS: The recurrence rate was
      lower in the perioperative treatment group than in non-treatment group (12/20,
      60.0% vs 11/16, 87.5%, P<0.05). The 1- and 2-year overall survival rates were
      70.8% and 47.1% for the chemotherapy group and 43.8% and 20.5% for the non
      chemotherapy group respectively, showing significant differences between them
      (P<0.05). The 1- and 2-year tumor-free survival rates were 60.6%, 40.5% and
      33.6%, 15.6% in the two groups, respectively, with also significant differences
      (P<0.05). CONCLUSIONS: Perioperative adjuvant treatment may significantly
      decrease the likeliness of tumor recurrence and prolong the survival of patients
      with advanced HCC after liver transplantation. Chemotherapy with ADM+5-Fu+CDDP
      can be effective and safe with only mild side-effects.

PMID- 17545035
TI  - [Changes of CD4+CD28- T cell and CD4+CD25+ regulatory T cell subsets in patients
      with coronary heart disease].
AB  - OBJECTIVE: To investigate the changes of CD4(+)CD28(-) T cell and CD4(+)CD25(+)
      regulatory T cell (Treg) subsets in patients with coronary artery disease (CAD).
      METHODS: Twenty-eight patients with angiographically established CAD were
      recruited in this study, including 16 with unstable angina (UA group) and 12 with
      stable angina (SA group). Eleven patients with chest pain syndrome served as the
      control group. The proportions of peripheral CD4(+)CD28(-) T cells and
      CD4(+)CD25(+) Treg subsets were determined with fluorescence-activated cell
      sorting (FACS). RESULTS: The proportions of CD4(+)CD25(+) Treg were significantly
      lower in UA group (6.55-/+2.45%) than in SA (14.01-/+4.92%) and control groups
      (13.55-/+3.87%). The proportions of CD4(+)CD28(-) T cells were significantly
      higher in UA group (10.55-/+4.76%) than in SA (2.64-/+1.33%) and control (2.75
      /+1.55%) groups. CONCLUSION: Alterations of circulating T-lymphocyte subsets
      occur in patients with UA. The changes of Treg and CD4(+)CD28(-) T cells may lead
      to breakdown of peripheral autoimmune tolerance and play an important role in the
      development and progression of CHD.

PMID- 17545036
TI  - [Detection of Helicobacter pylori in oral cavity of patients with recurrent
      aphthous ulcer].
AB  - OBJECTIVE: To investigate the association of recurrent aphthous ulcer (RAU) with
      Helicobacter pylori (Hp) infection and digestive diseases. METHODS: Saliva
      samples were collected from 82 patients with RAU and 74 healthy volunteers for Hp
      detection with PCR. RESULTS: The positivity rates of HP differed significantly
      between RAU patients and healthy volunteers (43.9% vs 16.2%, P<0.001). In the 82
      RAU patients, 22 (26.82%) were identified to have gastritis and peptic ulcer,
      whereas only 7 out of the 74 healthy volunteers (10.45%) had such digestive
      diseases, showing significant difference between them (P<0.01). CONCLUSION: Hp
      might in some way associate with RAU, which in turn is associated with an
      increased incidence of digestive diseases.

PMID- 17545037
TI  - [Toxic effects of CD-TK double suicidal gene system against prostate carcinoma
      cells].
AB  - OBJECTIVE: To evaluate the toxic effects of the CD-TK fusion gene systems against
      prostate carcinoma cell line RM-1 for assessing the value of suicidal gene
      therapy for prostate carcinoma. METHODS: CD-TK fusion gene and green fluorescent
      protein (GFP) gene were transfected into RM-1 cells through adenovirus vectors.
      RT-PCR was used to demonstrate successful transfection and transcription of the
      suicidal genes. The toxic effects of 5-FC and GCV used alone or in combination on
      the transfected cells were observed by MTT assay, with the non-transfected RM-1
      cells serving as control. RESULTS: Cytotoxic activity of CD/5-FC and TK/GCV
      systems against RM-1 cells was observed, and combined treatment with the two
      drugs resulted in significantly lowered survival of CD-TK-expressing cells
      (P<0.05). After exposure to 5-FC and GCV for 72 h, the survival rate of the
      transfected cells decreased to 71.56% and 47.27%, respectively, and their
      combined use resulted in a survival rate as low as 18.46%. CONCLUSION: CD-TK
      fusion double suicidal gene system can produce significantly stronger toxic
      effect against RM-1 cells in vitro than either of suicidal genes.

PMID- 17545038
TI  - [Comparison of mental health state and psychological capacities between college
      students with and without siblings].
AB  - OBJECTIVE: To compare the differences in mental health state and psychological
      capacities between Chinese college students with and without siblings. METHODS:
      The psychological status and capacities were evaluated with SCL-90, the Self
      Esteem Scale, Spheres of Control Scale, Security Questionnaire and Cattell 16-PF
      Questionnaire in 427 college students, and among the students who presented valid
      responses, 139 with and 139 without siblings were selected for this comparative
      study. RESULTS: The total score and average score of SCL-90 in college students
      without siblings were significantly lower than those in students with siblings
      (P<0.05); the scores of factors C, E, and F of 16-PF were significantly higher
      but the score of factor O significantly lower in the former group (P<0.05). The
      scores of certainty in control, interpersonal security and total score of
      security were significantly higher in the students without siblings (P<0.01).
      CONCLUSION: The mental health state and some of the psychological capacities are
      generally better in college students with siblings than in those without
      siblings.

PMID- 17545039
TI  - [Association between ADAM33 gene polymorphism and bronchial asthma in South China
      Han population].
AB  - OBJECTIVE: To investigate the association between the polymorphism of T(1) locus
      allele in ADAM33 gene and bronchial asthma in South China Han population.
      METHODS: Polymerase chain reaction-restriction fragment length polymorphism (PCR
      RFLP) and DNA sequencing were used to determine the polymorphism of T(1) locus
      allele in ADAM33 gene in 160 unrelated patients with asthma and 95 unrelated
      healthy controls from South China Han population. RESULTS: No significant
      difference was found in T(1) locus allele distribution frequency in populations
      of UK, US, Germany, Korea, and South China (Chi(2)=9.085, P=0.109). The
      frequencies of the genotypes (TT, TC, CC) were 80.6% (n=129), 16.9% (n=27) and
      2.5% (n=4) in the 160 asthmatic patients and 94.7% (n=90), 3.2% (n=3) and 2.1%
      (n= 2) in the 95 controls, respectively, showing a significant difference in the
      distribution of the genotypes (TT, TC, CC ) between asthmatic patients and
      healthy controls (Chi(2)=10.955, P<0.05). The frequencies of the alleles (T, C)
      were 0.891 and 0.109 in the asthmatic patients and 0.963 and 0.037 in the
      controls, respectively, showing also a significant difference in the allele
      frequency between them (Chi square =8.299, P<0.05). The presence of C allele of
      ADAM33 gene T1 locus was found to be a greater risk factor in asthmatic patients
      than in the healthy controls. The odds ratio (OR) of TC and TC+CC were 6.279
      (1.849-21.328) and 4.326 (1.620-11.550), respectively, with P value of 0.001 and
      0.002, respectively, in comparison with TT genotype. CONCLUSION: The polymorphism
      of T(1) locus allele in ADAM33 gene is associated with the susceptibility to
      asthma in South China Han population.

PMID- 17545040
TI  - [Expressions of Sca-1, CD24 and Muc1 in quiescent mammary glands of female rats].
AB  - OBJECTIVE: To investigate the expressions of the stem cell antigen-1 (Sca-1),
      Mucin1 (Muc1) and CD24 in quiescent mammary glands of female rats. METHODS: The
      expressions of CD24 and Sca-1 were detected in 6- and 9-week-old female rat
      mammary gland by Western blotting. Sections (4 microm) of 6- and 9-week-old
      female SD rat mammary gland were prepared to observe the expressions of Sca-1,
      Muc1 and CD24 by immunohistochemical labeling and immunofluorescence labeling.
      RESULTS: CD24 and Sca-1 in the mammary glands were expressed at lower level in 6
      week-old female rats than in 9-week-old female rats. Sca-1 expression was
      detected in the mammary gland ductus, branching ductus, and areas surrounding the
      gland alveolus; CD24 was expressed in the mammary gland branching ductus and fat
      pads, and also the regions surrounding the gland alveolus. Muc1 expression was
      localized in the mammary gland ductus and branching ductus. CONCLUSIONS: Sca-1-,
      CD24- and Muc1-positive cells may represent mammary gland progenitor cells,
      mammary gland stem cells, and mammary gland mature epithelium cells,
      respectively. This study provides some morphological evidences for identifying
      these cells, but they still need further verifications in cellular
      transplantation experiments.

PMID- 17545041
TI  - [Effects of two different antigen-loading methods on the activity of dendritic
      cell vaccine for colorectal carcinoma cell inhibition in vitro].
AB  - OBJECTIVE: To observe the changes in the activity of dendritic cells (DCs) after
      carcino-embryonic antigen (CEA) gene transfection mediated by recombinant adeno
      associated virus type2 (rAAV) and tumor cell lysate. METHODS: Immature DCs
      isolated from peripheral blood monocytes of HLA-A11-positive healthy volunteers
      were infected with the rAAV carrying CEA gene or loaded with tumor cell lysate.
      The surface markers of the DCs such as CD40, CD 1alpha, and CD86 were analyzed by
      flow cytometry. Interleukin-12 (IL-12) in the supernatants of DCs and interferon
      gamma (IFN-gamma) released by the cytotoxic T lymphocytes (CTLs) were determined
      by ELISA detection kit. The specific killing activity of CTL against LoVo cells
      was assessed by MTT assay. RESULTS: The DCs following antigen loading with the
      two methods both highly expressed CD40, CD86 and IL-12, and induced specific CTL
      that specifically recognized and killed LoVo cells, but the killing effect
      resulting from rAAV infection of the DCs was much better than that induced by
      tumor cell lysate loading. CONCLUSION: Both methods of antigen loading can induce
      mature DCs from peripheral blood monocyte cells, but rAAV infection of the DCs
      can be more effective than tumor cells lysate loading. DCs infected with rAAV may
      have the potential to serve as an adjuvant immunotherapy for patients with
      colorectal carcinoma.

PMID- 17545042
TI  - [Tumor necrosis factor-alpha regulates the proliferation and syndecan-4
      expression of human umbilical vein endothelial-like cells cultured in vitro].
AB  - OBJECTIVE: To investigate the effects of tumor necrosis factor-alpha(TNF-alpha)
      on syndecan-4 protein expression and proliferation of cultured human umbilical
      vein endothelial-like cells (HUVECs) in vitro. METHODS: HUVECs exposed to
      different concentrations of TNF-alpha(100, 20, 10, and 1 ng/ml) were cultured for
      24 h and 36 h to observe their proliferation in comparison with the control
      group. The cell proliferation rate was determined by non-radioactive MTS/PES
      assay. The expression of syndecan-4 protein was evaluated by immunoblotting
      technique using anti-syndecan-4 antibody. Results The proliferation rate of the
      endothelial-like cells was 1.956-/+0.214 in the control group, and 2.154-/+0.250,
      2.260-/+0.151, 2.118-/+0.205 and 2.106-/+0.136 in TNF-alpha-treated groups
      corresponding to TNF-alpha concentrations of 100, 20, 10 and 1 ng/ml at 24 h,
      respectively. It was shown that TNF-alpha significantly stimulated cell
      proliferation at the concentration above 1 ng/ml (P<0.05) as compared with the
      control group (P<0.05). The proliferation rate of the endothelial-like cell was
      1.915-/+0.236 in the control group, and 2.067-/+0.328, 2.207-/+0.150, 2.052
      /+0.126 and 2.051-/+0.180 in TNF-alpha-treated groups corresponding to TNF
      alphaconcentrations of 100, 20, 10 and 1 ng/ml at 36 h, respectively. The
      expression of syndecan-4 protein was significantly enhanced by TNF-alpha.
      CONCLUSIONS: TNF-alpha can stimulate HUVEC proliferation, and expression of
      syndean-4 may represent an additional component of the pro-inflammatory, growth
      stimulating pathways that are activated in response to changes in the vascular
      wall.

PMID- 17545043
TI  - [Procyanidins inhibit proliferation and promote apoptosis of the prostate cancer
      cell line LNCaP].
AB  - OBJECTIVE: To investigate the effects of procyanidins on proliferation and
      apoptosis of a hormone-dependent prostate cancer cell line LNCaP in vitro.
      METHODS: LNCaP cells were cultured in the presence of procyanidin (at 100, 200
      and 300 microg/ml, respectively). After 24, 48 and 72 h of culture, the
      morphological changes of LNCaP cells were examined, and the inhibition of cell
      proliferation was measured by MTT assay and cell apoptosis evaluated by flow
      cytometry. RESULTS: After procyanidins treatment, some LNCaP cells presented
      characteristic morphological changes. Procyanidins inhibited the growth of LNCaP
      cells in a concentration- and time-dependent manner. Flow cytometry analysis
      showed that procyanidins induced apoptosis of LNCaP cells and the percentage of
      apoptotic cells increased with the concentration of procyanidins administered and
      also the elongation of treatment time. CONCLUSION: Procyanidins inhibit the
      proliferation and promote the apoptosis of prostate cancer cells.

PMID- 17545044
TI  - [Microstructural observation of epileptic neurons in vitro by atomic force
      microscopy].
AB  - OBJECTIVE: To observe the microstructure of the cell membrane of epileptic
      neurons using atomic force microscopy (AFM). METHODS: Model of epileptic neurons
      was established by subjecting the neurons culture for 14 days in vitro to
      magnesium-free media treatment for 3 h. Patch clamp technique was applied to
      record the electrophysiological activity of the epileptic neurons. AFM was
      performed to observe and measure the microstructure of the cell membrane of the
      epileptic neuron. RESULTS: After a 3-hour treatment with magnesium-free media,
      the epileptic neurons displayed sustained epileptiform discharge, which continued
      after the neurons were returned to normal medium culture on day 14. Under AFM
      scanning size of 80 microm x 80 microm and 2 microm x 2 microm, no obvious
      difference in the morphology of the cell membrane was noted between epileptic and
      normal neurons; under the scanning size of 500 nm x 500 nm, small pits occurred
      in the cell membrane in both groups, but no significant difference was found in
      the dimension of the pits between the two groups (the diameter and depth of the
      pits was 114.86-/+9.33 nm and 5.71-/+0.69 nm in epileptic neurons, and 116.4
      /+9.13 nm and 5.69-/+0.71 nm in the control neurons, respectively, P>0.05).
      CONCLUSION: AFM provides a new method for observing neuronal membrane
      microstructure at nanometer resolutions. No significant alterations occur in the
      membrane of the neurons after a 3-hour magnesium-free media treatment.

PMID- 17545045
TI  - [Effects of angiotensin II receptor antagonist on rat podocyte injury in early
      diabetic nephropathy].
AB  - OBJECTIVE: To investigate nephrin and desmin expression in rat podocytes in early
      diabetic nephropathy (DN) and the rale of angiotensin II receptor antagonist in
      renal protection. METHODS: Rat models of DN established by a injection of a
      single dose of streptozotocin (STZ) were randomized into model group and
      irbesartan group, with rats without STZ injection as the normal control group.
      The rats in irbesartan group were subjected to daily intragastric irbesartan
      administration for 8 consecutive weeks, while those in the model group received
      only saline in the same manner. Upon completion of the treatment, the rats were
      sacrificed and pathological changes of the kidney were examined with optical and
      transmission electron microscope. Nephrin and desmin expressions in the podocytes
      were detected by immunohistochemistry. RESULTS: In rats with DN, irbesartan
      administration alleviated podocyte injury and significantly lowered the
      expression of nephrin and desmin (P<0.05). CONCLUSION: Angiotensin II receptor
      antagonist may offer renal protection against DN by alleviating structural and
      functional podocyte damage through decreasing nephrin expression in the
      podocytes.

PMID- 17545046
TI  - [Correlation between MHC class I-related chain A gene *008 allele and human
      cytomegalovirus infection].
AB  - OBJECTIVE: To investigate the correlation between MHC class I-related chain A
      (MICA) gene *008 allele and human cytomegalovirus (HCMV) infection. METHODS:
      MICA*008 allele was detected in 86 patients with chronic granulocytic leukemia
      and 81 unrelated normal individuals by way of sequence-specific primers (PCR
      SSP). Anti-HCMV IgM was also detected in the sera of these subjects with enzyme
      linked immunosorbent assay (ELISA). RESULTS: MICA*008 allele frequency was lower
      in patients with chronic granulocytic leukemia than in the control group (22.2%
      vs 34.3%, Chi(2)=4.98, P<0.05). The infection rate of HCMV was significantly
      higher in those individuals with genotype of MICA*008 (-) than in those with
      MICA*008 (+), and moderate correlation was suggested between MICA*008 and HCMV
      infection (C=0.5829, 0.6142). CONCLUSION: Individuals with MICA*008 positivity is
      not liable to HCMV infection, but those with MICA*008 (-) can be vulnerable to
      HCMV infection, suggesting an inverse correlation between MICA*008 allele with
      HCMV.

PMID- 17545047
TI  - [Gene expression profiles of K562 cells treated with total saponin of Panax
      ginseng].
AB  - OBJECTIVE: To investigate the effect of the total saponin of Panax ginseng (TSPG)
      on gene expression profile of K562 cells using microarray technique. METHODS: The
      total RNA were extracted and purified from K562 cells treated by 200 microg/ml
      TSPG for 3 days, and untreated K562 cells cultured in parallel served as the
      control. cRNAs were synthesized and labeled with Cy3 and Cy5 respectively. The
      labeled cRNA fragments were hybridized with Agilent human 1B 60 mer
      oligonucleotide microarray, which was then scanned to reveal the changes of gene
      expression profile in relation to TSPG treatment. RESULTS: Totally 362
      differentially expressed genes were identified in TSPG-treated K562 cells,
      including 20 up-regulated ones (consisting of metabolism-associated genes, signal
      transduction-associated genes and cell receptor-associated genes etc) and 342
      down-regulated ones (consisting of immunity and defense-associated genes, DNA
      binding and transcription genes, metabolism-associated genes and cell cycle
      associated genes etc). Changes in expressions of FOSL1, E2F2, CCNE2 and ODZ1 were
      confirmed by semi-quantitative RT-PCR. CONCLUSIONS: TSPG may induce changes in
      the gene expression profile in k562 cells possibly relevant to the anti-tumor
      mechanism of TSPG.

PMID- 17545048
TI  - [Association of p16, p53, Ki-67 expressions with high-risk human papilloma virus
      infection in cervical intraepithelial neoplasia].
AB  - OBJECTIVE: To investigate the association between p16, p53 and Ki-67 expression
      and high-risk human papilloma virus (HPV) infection in cervical intraepithelial
      neoplasia (CIN). METHODS: Using a self-prepared tissue microarray, p16, p53, and
      Ki-67 expression was detected in 243 cases of CIN and 30 cases of normal cervical
      epitheliums by immunohistochemistry, and high-risk HPV infection was detected by
      gene hybridization capture II. RESULTS: p16, p53 and Ki-67 expressions were all
      negative in normal cervical epitheliums, but all positive in CIN. The expression
      of p16 and Ki-67 was 88.2 (67/76) and 92.1% (70/76) in CIN grade 1, respectively,
      and both were 100% in CIN grades 2 and 3, and the intensity of positive
      expression was significantly correlated with CIN grade (P<0.001). The positive
      cells in CIN grade 1 were mostly within the lower 1/3 of the squamous epithelium,
      while in CIN grade 2, the positive cells involved the lower 2/3 of the epithelium
      layers; in CIN grade 3, more than 2/3 or almost the full thickness of the
      epithelium was involved, suggesting significant correlation between the
      involvement and CIN grades (P<0.001). p53 expression was positive in 31.6%
      (24/76) of the cases in CIN grade 1, 53.4% (47/88) in CIN grade 2 and 58.2%
      (46/79) in CIN grade 3, and the intensity of positive expression was in
      significantly correlation with CIN grades (P<0.001), but no significant
      difference occurred between CIN 2 and CIN 3. High-risk HPV were detected in 37/52
      (71.2%) of the cases in CIN grade 1, 50/58 (86.2%) in CIN 2 and 50/55 (90.9%) in
      CIN 3, and the relative DNA amount was significantly correlated with CIN grade
      (P<0.001), but there as no significant difference between CIN 2 and CIN 3.
      CONCLUSIONS: High-risk HPV infection and p16, p53, Ki-67 overexpression all play
      important roles in the carcinogenesis of cervical precancerous lesion, and both
      p16 and Ki-67 expression are useful markers in diagnosis and staging of CIN.

PMID- 17545049
TI  - [Cell biological study of adipose-derived stem cells].
AB  - OBJECTIVE: To explore an approach to isolate and culture adipose-derived stem
      cells (ASCs) from the adipose tissue of liposuction aspirates, and conduct
      observations of the cell growth kinetics, morphology, differentiation capability,
      cell aging, and surface marker profiles. METHODS: From the liposuction aspirates,
      ASCs were isolated by means of enzymatic digestion, and the appearance of the
      cultured cells was observed. The cell viability was evaluated with MTT
      chromatometry and cell growth curve was generated. Flow cytometry was performed
      for cell cycle analysis, and acridine orange staining was utilized for cell aging
      evaluation. The expressions of the cell surface marker profiles were detected by
      flow cytometry and immunohistochemistry. Adipogenic differentiation of ASCs was
      assessed by Oil Red O staining. RESULTS: Primarily cultured ASCs adhered to the
      culture plates with a fibroblastic appearance and strong proliferation capacity
      as shown by MTT chromatometry. ASCs also showed characteristic stem cell cycle.
      Acridine orange staining of the ASCs at passages 3, 4, 6, and 8 did not reveal
      evidence of obvious cell aging. The expressions of CD29, CD44, and CD34 were
      observed in ASCs by flow cytometry while HLA-DR or CD133 expression was not
      detected. Expressions of VA factor, CD31, CD34, CD105 and SMA were observed in
      ASCs by immunohistochemistry. Oil Red O staining of the ASCs after 2 weeks of
      culture demonstrated numerous intracellular lipid droplets. CONCLUSION: ASCs can
      be isolated from autologous liposuction aspirates of human via enzymatic
      digestion and cultured ex vivo. These cells are fibroblast-like cells expressing
      cell surface markers of stem cells with strong proliferative ability, and can be
      induced to differentiate into adipose tissue.

PMID- 17545050
TI  - [Distribution and drug resistance spectrum analysis of 2478 clinical bacterial
      and Candida isolates].
AB  - OBJECTIVE: To investigate the distribution and drug resistance spectrum of
      clinical bacterial and Candida isolates. METHODS: Most of the bacterial isolates
      were identified using automated BD Phoenix, and a few with K-B method carried out
      manually. Candida isolates were identified by color-display plate and K-B method.
      RESULTS: The most common isolates in the 2478 strains were P. aeruginosa (15.6%),
      E. coli (11.5%), C. albicans (9.6%), K. pneumoniae (9.3%), S. aureu (8.2%), and
      S. epidermidis (7.5%). In gram-negative isolates, the antibiotics with the lowest
      resistance rate were meraopenem (14.4%), cefoperazone/Sulbactam (14.8%), Imipenem
      (21.9%), piperacillin/tazobactam (27.4%), ceftazidime (30.0%), amikacin (31.1%),
      and cefepime (33.1%). The detection rate of E.coli and K. pneumoniae isolates
      producing extended spectrum beta-lactamase (ESBLs) were 47.4% and 37.3%
      respectively. In gram-positive isolates, the antibiotics with the lowest
      resistance rate were vancomycin (0.9%), teicoplanin (1.1%), nitrofurantoin
      (6.9%), amikacin (20.1%), chloramphenicol (30.7%), and cefoperazone/sulbactam
      (31.5%). The methecillin-resistant rates of S. aureu , S. epidermidis, and S.
      haemolyticus were 57.1%, 65.0%, and 66.0%. For Candida isolates, the most
      sensitive antibiotics were amphotericin B (0.3%), nystain (0.3%), itraconazole
      (5.6%), fluconazole (9.4%), and fluorocytosine (9.4%). CONCLUSION: The results
      suggest high rate of ESBL production and oxacillin resistance of the bacteria
      isolated in the hospital. More rational use of antimicrobial agents is crucial
      for reducing the drug-resistance of the bacteria, and effective measures must be
      taken to reduce dissemination of multidrug-resistant bacteria.

PMID- 17545051
TI  - [PDX-1 gene transfection and expression in bone marrow stromal cells-derived
      nestin-positive cells].
AB  - OBJECTIVE: To introduce the eukaryotic expression vector pEGFP-C1-PDX-1 into
      nestin-positive cell derived from bone marrow stromal cells by nucleofection and
      optimize the conditions for transfection. METHODS: The recombinant plasmid was
      transfected into bone marrow stromal cells-derived nestin-positive cells with
      varied DNA quantities or the serum concentration in the medium. The expression of
      PDX-1 gene in the transfected cells was detected by RT-PCR. RESULTS: Satisfactory
      efficiency of transfection was achieved with the DNA quantity of 2-10 microg and
      medium serum concentration of 20%. PDX-1 expression was detected in the
      transfected cells by RT-PCR. CONCLUSION: The optimized transfection conditions
      result in enhanced efficiency of PDX-1 gene transfection into nestin-positive
      cells derived from bone marrow stromal cells, which may serve as the seed cells
      in tissue-engineering.

PMID- 17545052
TI  - [Effects of Huafenqinutang and vardenafil for treatment of chronic
      prostatitis/chronic pelvic pain syndrome with concomitant erectile dysfunction].
AB  - OBJECTIVE: To evaluate the effects of Huafenqinutang combined with vardenafil for
      the treatment of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) with
      erectile dysfunction. METHODS: One hundred and thirty-eight cases diagnosed as
      CP/CPPS with erectile dysfunction were randomized into trial group (70 cases) and
      control group (68 cases) for treatment with Huafenqinutang for 8 weeks, and in
      the former group, vardenaffil was added since the fifth weeks. All the cases were
      evaluated according to NIH-CPSI and IIEF-5 scores at 4 weeks and 8 weeks,
      respectively. RESULTS: At the end of the fourth weeks, NIH-CPSI score was 13.1
      /+4.7 in the trial group and 13.3-/+4.5 in the control group, which were
      comparable between the two groups (P>0.05) but significantly decreased compared
      with the pre-treatment scores in both groups (P<0.01). IIEF-5 score was also
      similar between the two groups (14.1-/+3.3 vs 14.3-/+5.0, P>0.05) but
      significantly increased compared with the pre-treatment scores in both groups
      (P<0.01). At the end of the eighth week, NIH-CPSI score was 7.8-/+2.2 and IIEF-5
      score 20.1-/+4.4 in the trial group, which were significantly different from
      those at the end of the fourth week (P<0.01). In the control group, NIH-CPSI
      score was 12.7-/+2.3 and IIEF-5 score 14.3-/+4.5 at the eighth week, similar to
      those at the end of the fourth week (P>0.05). There were significant differences
      in NIH-CPSI and IIEF-5 scores between the 2 groups (P<0.01), and the change of
      NIH-CPSI score was negatively correlated with IIEF-5 score in the trial group (r=
      0.89, P<0.01). CONCLUSION: For patients with CP/CPPS with erectile dysfunction,
      Huafenqinutang treatment in combination with vardenafil can effectively improve
      the erectile functions and decrease the NIH-CPSI score to favor the recovery from
      CP/CPPS.

PMID- 17545053
TI  - [Association between transforming growth factor beta-1 gene polymorphism and
      chronic allograft nephropathy].
AB  - OBJECTIVE: To investigate the association between transforming growth factor beta
      1 (TGF-beta1) gene polymorphism and chronic allograft nephropathy (CAN). METHODS:
      Fifty patients with failed renal allografts and clinically and
      histopathologically confirmed CAN were enrolled in this study along with another
      50 renal transplant recipients with normal graft function. The DNA extracted from
      whole blood of the patients was amplified with PCR with sequence-specific primers
      for determining TGF-beta1 genotypes (position +869, codon 10 and position +915,
      codon 25). According to documented descriptions, the patients were classified
      into high and moderate-to-low cytokine production genotypes. The distribution
      frequencies of high production genotypes was then compared between CAN and non
      CAN groups. To eliminate interference in the analysis of the association between
      TGF-beta1 polymorphism and CAN, other possible risk factors for CAN were
      screened, including the patients' gender, age, HLA match, delayed graft function,
      acute rejection, immunosuppressive regimen, cytomegalovirus infection,
      hypertension, and high cholesterol. RESULTS: CAN patients showed significantly
      greater proportion of high cytokine production genotype than the non-CAN group
      [70% (35/50) vs 38% (19/50), Chi(2)=10.306, P=0.001). Of the screened risk
      factors for CAN, only acute rejection showed some difference between the two
      groups, but analysis after subgrouping according to acute rejection did not
      suggest its influence on CAN, which supports the result that the rate of high
      production genotype was significantly higher in CAN group than in the non-CAN
      group. CONCLUSION: Most CAN patients have high TGF-beta1 production genotype,
      which might be a risk factor for CAN after renal transplantation. TGF-beta1
      genotyping can be of value in predicting the risk of CAN after renal
      transplantation.

PMID- 17545054
TI  - [Expression of hypoxia-inducible factor-1alpha in endometriosis].
AB  - OBJECTIVE: To detect the expression of hypoxia-inducible factor-1alpha(HIF
      1alpha) in endometriosis and explore the possible role of HIF-1alpha in the
      pathogenesis of endometriosis. METHODS: Immunohistochemistry was performed to
      examine the expression of HIF-1alpha in 20 normal endometrium, 20 ectopic
      endometrium and 68 eutopic endometrium specimens from 68 endometriosis patients,
      and the results were analyzed statistically. RESULTS: The expression of HIF
      1alpha was significantly increased in ectopic endometrium than in normal
      endometrium (P<0.01), and the expression did not undergo changes with the normal
      menstrual cycle in the three types of endometrium. CONCLUSION: HIF-1alpha
      expression increases in ectopic endometrium, suggesting that HIF-1alpha plays an
      important role in the pathogenesis of endometriosis.

PMID- 17545055
TI  - [Comparison of transdermal permeation in vitro of lidocaine tincture and
      microemulsion].
AB  - OBJECTIVE: To compare lidocaine tincture and microemulsion for their transdermal
      permeation. METHODS: The experimental model for percutaneous administration of
      lidocaine preparations in vitro was prepared using modified Franz diffusion cell.
      RESULTS: The accumulated infiltration amount of lidocaine microemulsion in unit
      area was higher than that in its cream or tincture preparations. CONCLUSION: The
      transdermal permeation of lidocaine microemulsion in vitro can be more efficient
      than that of the tincture preparation, and the permeation is linearly dependent
      on the dose administered within a certain range.

PMID- 17545056
TI  - [Protective effects of lidocaine against lung injury after hemorrhagic shock in
      rabbits].
AB  - OBJECTIVE: To study the protective effect of lidocaine against lung injury after
      hemorrhagic shock in rabbits. METHODS: Eighteen healthy rabbits were randomly
      divided into 3 groups (n=6), namely lidocaine group (group L), hemorrhagic shock
      group (group H) and control group (group C). Hemorrhagic shock model was
      established in rabbits in groups L and H, and the venous blood samples were
      collected for measurement of plasma malondialdehyde (MDA) and superoxidedismutase
      (SOD) before phlebotomy (T0), 2 h after hemorrhagic shock (T1) and 2 h after
      resuscitation (T2). Blood samples were also taken for measurement of MDA and SOD
      at the same time points in group C. The wet to dry weight ratio of the lung (W/D)
      was measured at T2. RESULTS: MDA level was significantly lower while SOD level
      significantly higher in group L than in group H (P<0.05). The W/D ratio in group
      L was reduced significantly as compared with that in group H (P<0.05).
      CONCLUSION: Lidocaine can remarkably alleviate lung injury after hemorrhagic
      shock by inhibiting MDA production and increasing SOD content.

PMID- 17545057
TI  - [Clinical effect of removable lingual arch plus auxiliary spring for dental arch
      expansion].
AB  - OBJECTIVE: Observe the clinical effect of removable lingual arch plus auxiliary
      spring for convenient dental (especially mandibular) arch expansion. METHODS:
      Seventeen patients with dental arch constriction complicated by mild dental
      crowding were enrolled in this study, including 9 requiring maxillary arch
      expansion and 8 necessitating mandibular expansion. The patients were divided to
      two groups at random for arch expansion with removable lingual arch plus
      auxiliary spring and with Quad-helix, respectively, and the effect of arch
      expansion was compared between the two groups. RESULTS: After 8 weeks of arch
      expansion, the average width of U4-U4 and U5-U5 in removable lingual arch group
      was enlarged by 2.2 mm and 3.0 mm, and that in Quad-helix group by 2.3 mm and 3.5
      mm, respectively, showing no significant differences between the two groups
      (P>0.05). After 12 weeks of treatment, the average width of L4-L4 and L5-L5 in
      the former group was enlarged by 2.3 mm and 2.5 mm, respectively, significantly
      greater than that in the latter group (1.0 mm and 1.2 mm, P<0.05). CONCLUSION:
      Removable lingual arch plus auxiliary spring allows significant expansion of the
      middle segment of the dental arch (bicuspids), and can be more effective than
      Quad-helix for mandibular arch expansion.

PMID- 17545058
TI  - [High-performance liquid chromatography for determining plasma alpha-lipoic acid
      in New Zealand rabbits].
AB  - OBJECTIVE: To establish a method for determining the content of alpha-lipoic acid
      in New Zealand rabbit plasma. METHODS: Alpha-lipoic acid in the plasma samples
      was purified by solid-phase extractor and analyzed on an HYPERSIL C18 column with
      isocratic mobile phase consisting of potassium dihydrogen phosphate-acetonitrile
      (50:50, v/v) at a flow rate of 1.0 ml/min and detection wavelength of 230 nm.
      RESULTS: The standard curve was linear in the range of 5-100 microg/L (r=1) and
      the average recovery was 77.4%-82.1%. The relative standard deviations of intra
      day and inter-day assay were within 1.5%-8.9%. CONCLUSION: The method is
      sensitive, accurate and simple for determining plasma alpha-lipoic acid levels in
      New Zealand rabbits.

PMID- 17545059
TI  - [From meridians and acupoints to self-supervision and control system: a
      hypothesis of the 10th functional system based on anatomical studies of digitized
      virtual human].
AB  - Chinese acupuncture and moxibustion has been widely accepted as a useful
      therapeutics all over the world, but its mechanism has not been fully defined.
      For this purpose, a reticular framework of whole-body fascia and connective
      tissues has been established by means of digitized virtual human technique. The
      virtual acupoints represented three-dimensionally were compared with the sites
      for stimulation in practice of traditional Chinese medicine (TCM) acupuncture
      therapy. The results showed that the fascial network constituted by the
      connective tissues may be the anatomical basis for acupuncture therapy. We found
      that the acupoints were mainly located where thick connective tissues were
      present. In this fascial network, sensitive nerve endings, active cells and
      lymphatic vessels abounded in the sites with thick connective tissue, and
      needling at these sites induced definite biological effects. In light of
      biological phylogeny and embryo development, we believe that the connective
      tissue network may constitute a new functional system in the human body, the Self
      supervision and control system (Fasciology), which provides a theoretical base
      for acupuncture therapy.

PMID- 17545060
TI  - [Relationship between radiosensitivity of nasopharyngeal carcinoma and MDR1 gene
      polymorphism].
AB  - OBJECTIVE: To investigate the relationship between human multidrug resistancel
      gene (MDR1) polymorphisms and the radiosensitivity of nasopharyngeal carcinoma
      (NPC). METHODS: Blood samples were collected from 59 NPC patients, who were
      devided into radiosensitive or radioresistant groups according to their responses
      to radiation therapy. The genotypes for MDR1 polymorphisms (G2677T in exon 21 and
      C3435T in exon 26) and their haplotypes were determined by PCR and restriction
      fragment length polymorphism analysis. The results were further confirmed by
      sequencing. RESULTS: The 3435CC genotype was associated with a significantly
      better response to radiotherapy than combined 3435 CT and TT genotype (P=0.026).
      The 2677GG genotype was also associated with a better response in comparison with
      combined 2677 GT and TT genotype, but this relation was not statistically
      significant. Patients with 2677G-3435C haplotype had a significant better
      response to radiotherapy than those with the other haplotypes (P=0.017).
      CONCLUSION: The MDR1 G2677T and C3435T polymorphisms may help predict the
      response to radiotherapy in NPC patients.

PMID- 17545061
TI  - [Cloning, prokaryotic expression and immunoreactivity evaluation of
      Angiostrongylus cantonensis galectin].
AB  - OBJECTIVE: To construct the recombinant plasmid for Angiostrongylus cantonensis
      (AC) galectin (GAL) cDNA and analyze the immunological activity of the
      recombinant protein. METHODS: AcGAL cDNA was screened from the cDNA library and
      amplified by PCR. The amplified fragment was subcloned into the expression vector
      pET32a(+) and expressed in E.coli. The inclusion body was washed, degenerated,
      refolded by dialysis, and condensed for SDS-PAGE and Western blot analysis of the
      protein. RESULTS: For the first time the full-length cDNA of AcGAL was cloned
      (GenBank GeneID: DQ384534). Restriction enzyme digestion indicated that the
      recombinant plasmid pET32a(+)-AcGAL was successfully constructed. SDS-PAGE
      analysis confirmed high expression of the recombinant protein AcGAL in E.coil in
      the form of inclusion bodies, which possessed good immunoreactivity as shown by
      Western blot analysis. CONCLUSION: The success in cloning and identification, the
      recombinant AcGAL may provide basis for further diagnostic study of
      angiostrongyliasis.

PMID- 17545062
TI  - [Clinical application of gonadotropin-releasing hormone antagonist in Chinese
      women undergoing controlled ovarian hyperstimulation for in vitro fertilization
      and embryo transfer].
AB  - OBJECTIVE: To analyze the clinical characteristics and cycle outcome of Chinese
      women with gonadotropin-releasing hormone (GnRH) antagonist treatment during
      controlled ovarian hyperstimulation (COH) for in vitro fertilization and embryo
      transfer (IVF-ET). METHODS: A retrospective review was conducted in patients who
      completed 54 consecutive cycles of IVF-ET with GnRH antagonist treatment for
      luteinizing hormone (LH) surge prevention. Descriptive statistics were recorded
      for the patients' age, GnRH treatment duration (days) and dose, timing and
      duration of GnRH antagonist treatment, serum E2 and LH level on the day of
      antagonist use and hCG injection, number of oocytes retrieved, and clinical
      pregnancy rate. RESULTS: The clinical pregnancy rate was 46.2% per ET cycle for
      GnRH antagonist group and 56.8% in GnRH agonist group, showing no significant
      difference between the two protocols. The age of the patients with GnRH
      antagonist averaged 35.7-/+3.8 years. Gn and GnRH antagonist treatment lasted for
      8.5-/+1.6 and 4.5-/+1.1 days, respectively. On the day of ovulation triggered by
      hCG, the serum estradiol level was 1616.7-/+721.1 pg/ml, and a mean of 7.4-/+4.6
      oocytes was collected per retrieval. The number of the embryos transferred was
      2.4-/+0.6, with an implantation rate of 27.7%, resulting in a clinical pregnancy
      rate of 50.0% in the fixed protocol (antagonist initiation on day 4 or 5 of
      stimulation) and 37.5% in the flexible protocol (antagonist treatment initiated
      for a follicle of 12-15 mm, on day 6 to 9 of stimulation). CONCLUSIONS: GnRH
      antagonists treatment results in good outcomes and can be safe, short, convenient
      and effective for Chinese women undergoing COH for IVF. GnRH antagonist treatment
      can be initiated on day 4 to 9 of Gn stimulation to obtain comparable pregnancy
      rate.

PMID- 17545063
TI  - [Expression of alpha7-nAChR on rat hippocampal astrocytes in vivo and in vitro].
AB  - OBJECTIVE: To investigate the expression of alpha7-nAChR on rat hippocampal
      astrocytes in vivo and in vitro. METHODS: Rat hippocampus was isolated and cut
      into 30-microm cryosections with anti-GFAP antibody staining followed by staining
      for alpha7-nAChR. The cultured astrocytes obtained from newborn rat (1-2 days
      old) hippocampus were identified with GFAP, and the expression of alpha7-nAChR
      was measured by fluorescein isothcyanate-tagged alpha-bungarotoxin staining
      analysis and double immunolabeling. RESULTS: The localization of alpha7-nAChR was
      visualized in green with fluorescein isothiocyanate labeled IgG, whereas that of
      GFAP in red with Texas red-labeled IgG in the hippocampal slices, and the yellow
      spots indicating colocalization of the two fluorescent probes was shown in a
      merging image. alpha-bungarotoxin-binding nicotinic receptors were clustered, and
      the colocalization of alpha7-nAChR and GFAP on the cultured hippocampal
      astrocytes was visualized with the two fluorescent probes. CONCLUSION: The
      expression of alpha7-nAChR is identified on hippocampal astrocytes in vivo and in
      vitro.

PMID- 17545064
TI  - [Synthesis and characterization of chitosan-DNA nanoparticles as gene carriers].
AB  - OBJECTIVE: To prepare chitosan nanoparticles (NPs) as gene carriers and study its
      pharmaceutical characteristics and gene transfection efficiency in vitro.
      METHODS: The plasmid expressing green fluorescent protein (pGFP) was used as the
      reporter gene, and the chitosan-pGFP NPs were prepared using a complex
      coacervation process. The binding of pDNA was evaluated by agarose gel
      electrophoresis analysis, and the encapsulation rate was determined with
      colorimetry. The size distribution and polydispersity of the NPs were measured by
      nanoparticle size analyzer, and their morphologies observed by atomic force
      microscope. The transfection studies were performed with LoVo cells in vitro.
      RESULTS: The results of gel electrophoresis demonstrated full binding of chitosan
      with the pDNA by electrostatic interaction. The encapsulation rates for these NPs
      all exceeded 90%. The morphology of the chitosan NPs was mostly spherical and
      well distributed, with a mean diameter of about 209 nm and polydispersity of
      0.32. The in vitro transfection of chitosan-pGFP NP was efficient in LoVo cells
      and the expression of green fluorescent proteins was observed under fluorescent
      microscope. CONCLUSIONS: Chitosan NP prepared by complex coacervation can bind to
      the pDNA efficiently with high encapsulation rate and diameter distribution of
      100 to 500 nm. These NPs allow efficient delivery of the reporter genes into
      cells in vitro for their expression. The chitosan-pDNA NPs may serve as an
      effective non-viral carrier for delivery of nucleotides into cells.

PMID- 17545065
TI  - [Polymorphism of 12 Y-STR loci in Guangzhou Han population and its application in
      forensic medicine].
AB  - OBJECTIVE: To investigate the allele frequency distribution, gene diversity and
      haplotype diversity of 12 Y-specific short tandem repeats (STR) in Guangzhou Han
      population and evaluate their forensic application. METHODS: Twelve Y-STR loci in
      401 unrelated male Han individuals in Guangzhou were amplified with PowerPlex(R)
      Y System, and the PCR products were detected with 3100 Genetic Analyzer. RESULTS:
      The data of allele distribution and gene diversity of the 12 Y-STR loci were
      obtained from these individuals. A total of 398 haplotypes were observed and the
      overall haplotype diversity for the 12 Y-STR loci was 0.99997. The DNA samples of
      13 different species of animals were amplified and no specific products were
      observed. Different tissues from the same individual exhibited the same Y-STR
      haplotype. CONCLUSION: The 12 Y-STR loci exhibit high genetic polymorphism and
      are of important value in understanding of the human origin, individual
      identification for mixed male/female DNA samples and paternity identification.

PMID- 17545066
TI  - [Hepatocyte growth factor enhances protein synthesis in cardiomyocytes exposed to
      gamma-ray irradiation].
AB  - OBJECTIVE: To investigate the protective effect of hepatocyte growth factor (HGF)
      on protein synthesis in rat cardiomyocytes exposed to gamma-ray irradiation.
      METHODS: Primary cultured cardiomyocytes were irradiated with single-dose (20 Gy)
      gamma ray in the absence or presence of HGF (40 ng/ml) added in the cell culture
      3 h before the exposure. Forty-eight hours after irradiation, the total cellular
      protein was measured and cell cycle analyzed by flow cytometry. The cardiomyoctes
      were also infected with AdGFP 48 h after irradiation and the fluorescence
      intensity of the green fluorescence protein (GFP) in the cells determined by flow
      cytometry 48 h after infection. RESULTS: The protein synthesis was decreased
      significantly in the irradiated cardiomyocytes as compared with the control group
      (P<0.01), but was remedied significantly by incubation of the cells with HGF
      before the exposure (P<0.05). Flow cytometry revealed much lower mean
      fluorescence intensity (MFI) of GFP in irradiated cardiomycytes than in cells
      without the exposure (P<0.01); The MFI was higher in HGF-treated cardiomyocytes
      than in cells without HGF treatment following the exposure (P<0.01). CONCLUSION:
      Gamma ray irradiation inhibits protein synthesis in cardiomyocytes, and HGF may
      attenuate this effect of gamma ray exposure for cardiomyocyte protection.

PMID- 17545067
TI  - [Microsurgical anatomy of the perforating arteries in the superior space of the
      internal carotid artery through a pterional approach].
AB  - OBJECTIVE: To study the microanatomy of the perforating arteries in the superior
      space of the internal carotid artery visualized through a pterional approach.
      METHODS: Twelve (24 sides) perfused cadaver heads were dissected via the
      pterional approach, and the perforating arteries in the superior space of the
      internal carotid artery were studied under microscope. The diameter, course and
      distribution in the anterior perforated substance of the perforating arteries
      were recorded. RESULTS: All the perforating arteries exposed lied on the side of
      the brain tissue. The carotid bifurcation on 8 sides had perforating arteries,
      and 11 sides showed medial lenticulostriate artery of the middle cerebral
      arteries, with short course and overlapped with another perforating arteries upon
      entry into the anterior perforated substance. On 4 sides, the medial
      lenticulostriate artery coincided with the perforating arteries in A1. All 24
      sides showed middle lenticulostriate artery and lateral lenticulostriate artery
      of the middle cerebral arteries. Most of the lenticulostriate arteries originated
      from the anterior segment of the bifurcation of the middle cerebral arteries. The
      earlier bifurcation occurred in M1 of the middle cerebral arteries, the more
      perforating arteries originated. On 22 sides, the anterior cerebral arteries had
      perforating arteries with many branches, and fewer perforating arteries in a main
      artery were associated with greater diameter of them. CONCLUSION: The superior
      space of the internal carotid artery allows a space for operation, and in some
      cases, part of the medial leticulostriate arteries and A1 perforating arteries
      can be severed to obtain larger space for the operation.

PMID- 17545068
TI  - [Spatiotemporal pattern analysis of event-related potentials elicited by
      emotional Stroop task].
AB  - OBJECTIVE: To investigate the spatiotemporal pattern of event-related potentials
      (ERPs) induced by emotional Stroop task. METHODS: The ERPs of 19 channels were
      recorded from 13 healthy subjects while performing emotional Stroop task by
      pressing the buttons representing the colors in which the words denoting
      different emotions were displayed. A repeated-measures factorial design was
      adopted with three levels (word valence: positive, neutral and negative). The
      result of ERP analysis was presented in the form of statistical parametric
      mapping (SPM) of F value. RESULTS: No significant difference was found in either
      reaction time or accuracy. The SPM of ERPs suggested significant emotional
      valence effects in the occipital region (200-220 ms), the left and central
      frontal regions (270-300 ms), and the bilateral temporal and parietal cortex (560
      580 and 620-630 ms, respectively). CONCLUSION: Processing of task-irrelevant
      emotional valence information involves the dynamic operation of extensive brain
      regions. The ERPs are more sensitive than the behavioral indices in emotional
      evaluation.

PMID- 17545069
TI  - [Sinerem labeling and MRI tracking of neural stem cells in vivo and in vitro].
AB  - OBJECTIVE: To label rat neural stem cells (NSCs) with the complex of Sinerem, the
      ultrasmall superparamagnetic iron oxide (USPIO), and poly-L-lysine (PLL), and
      evaluate the feasibility of tracking the labeled cells with magnetic resonance
      imaging (MRI) in vitro and in vivo. METHODS: Sinerem was incubated with PLL to
      obtain the complex of Sinerem-PLL. The mesenchymal stem cells (MSCs) isolated
      from the bone marrow of SD rats were cultured and induced to differentiate into
      the neural stem cells. The second-passage cells were cultured overnight with the
      Sinerem-PLL complex, after which Prussian blue staining and transmission electron
      microscopy were performed to observe the nanoparticles in the cytoplasm. Cell
      apoptosis assay was performed to assess the cell viability 1 day, 1 week, and 2
      weeks after the labeling. Cell tracking with 4.7 MR system was carried out in
      vivo and in vitro using T(2)WI and T(2)*WI sequences. RESULTS: The NSCs could be
      effectively labeled with Sinerem-PLL complex with the labeling efficiency
      exceeding 95%. Prussian blue staining showed numerous blue iron particles in the
      cytoplasm, and under transmission electron microscope, these particles
      accumulated in the endosomes/lysosomes. The labeling did not significantly affect
      the cell viability and proliferation. Remarkable low signal density changes of
      the labeled cells was seen on T(2)WI and T(2)*WI in vivo and in vitro.
      CONCLUSION: NSCs can be effectively labeled with Sinerem-PLL complex, and MRI can
      be used to track the labeled cells in vivo and in vitro.

PMID- 17545070
TI  - [Improved reconstruction for PROPELLER data in magnetic resonance imaging based
      on fuzzy enhancement].
AB  - To improve the conventional reconstruction algorithm for PROPELLER MRI data, we
      propose a new algorithm based on fuzzy enhancement. The motion parameters were
      extracted from fuzzy enhanced images reconstructed through zero-padding strips.
      After motion compensation, the image was obtained through gridding
      reconstruction. The experiment results showed that this algorithm could estimate
      and compensate the motion more robustly and precisely, and the motion artifacts
      could be better suppressed to obtain improved image quality.

PMID- 17545071
TI  - [AF172993 sequence of Plunc in GenBank database is not the complete CDS].
AB  - OBJECTIVE: To determine AF172993 sequence is either the complete CDS or a
      transcript variant. METHODS: RT-PCR was used to amplify the CDS sequence of
      Plunc, which was subsequently cloned into the pEGFP-N1 eukaryotic expression
      vector. After bi-directional sequence analysis, the sequence obtained was blasted
      against the AF172993 sequence, nr database and human genome database. RESULTS: In
      CDS of the new cloned sequence, the 658 base A in the AF172993 sequence was
      replaced by C, and the corresponding genetic code was also converted from AAG to
      CAG, leading to the alteration of the amino acid Gln to Lys. In addition, the
      base C at the 658 position of the CDS showed perfect match with the base C at
      2094188 position in human chromosome 20. CONCLUSION: The base A at the 658
      position of AF172993 sequence of Plunc is a mutation site, which alters the
      coding of the amino acid. AF172993 sequence is actually a transcript variant of
      Plunc, and the annotation to AF172993 in GenBank database is not correct and need
      to be revised.

PMID- 17545072
TI  - [Targeted killing of colorectal tumor cells by lentiviral constructs containing
      CD/TK suicide genes and KDR promoter].
AB  - OBJECTIVE: To investigate the selective killing of colorectal tumor cells by
      lentivirus-mediated double suicide gene under the regulation of KDR promoter.
      METHODS: 293T packaging cells were transfected with the plasmid FGW-KDRP-CD/TK to
      obtain the infectious viruses. KDR-expressing LoVo cells and LS174T cells that
      did not produce KDR were transfected with the recombinant virus, and the
      transfection efficiency was evaluated by the fluorecence microscope. RT-PCR was
      employed to examine the expression of CDglyTK. After treatment of the cells with
      5-FC and GCV, the killing effects on the two cell lines were evaluated. RESULTS:
      The recombinant construct showed similar infection rate of the two cell lines. RT
      PCR demonstrated that CDglyTK gene was expressed only in LoVo cells infected with
      FGW-KDRP-CD/TK but not in LS147T cells, and the sensitivity of the two cell lines
      to the prodrugs was significantly different (P<0.001). The killing effect of the
      double suicide gene was much stronger than that of single suicide gene
      administered (P<0.001). CONCLUSION: The double suicide gene driven by KDR
      promoter has specific killing effect on the KDR-expressing colorectal tumor
      cells.

PMID- 17545073
TI  - [Apoptosis induction of rhesus peripheral blood lymphocytes].
AB  - OBJECTIVE: To establish a method for inducing apoptosis of rhesus peripheral
      blood lymphocytes (PBLs). METHODS: Rhesus PBLs were irradiated with X-ray, (60)Co
      gamma-rays and ultraviolet (UVC254 nm), respectively, and the cell apoptosis was
      evaluated with flow cytometry using annexin-V staining and propidium iodide
      staining. RESULTS: X-ray and (60)Co gamma-ray irradiation induced only low
      apoptotic rates of the PBLs, and UVC resulted in the highest apoptotic rate of
      about 60%. UVC irradiation of the PBLs in RPMI supplemented with 10% heat
      inactivated fetal calf serum for 60 min at a distance of 20 cm led to an early
      apoptotic rate of 58.85% and necrotic rate of 11.5%. The apoptotic rate of PBLs
      increased in a dose- and time-dependent fashion. CONCLUSION: For inducing
      apoptosis of the rhesus PBLs, UVC can be more effective than X-ray and (60)Co
      gamma-ray. The highest apoptotic rate can be achieved when the rhesus PBLs in
      RPMI supplemented with 10% heat-inactivated fetal calf serum are exposed to UVC
      for 60 min at the distance of 20 cm.

PMID- 17545074
TI  - [Differential expression of isocitrate lyase in P. marneffei phagocytized by
      nonstimulated and stimulated murine macrophages].
AB  - OBJECTIVE: To investigate the differential expression of isocitrate lyase in
      Penicillium marneffei phagocytized by nonstimulated and stimulated murine
      macrophages, and explore the role of glyoxylate pathway in pathogenesis of
      Penicilliosis marneffei. METHODS: Penicillium marneffei conidia and Raw264.7
      cells were incubated in 16 cultures, which were divided to 4 groups for treatment
      with N-monomethyl-L-arginine (LNMMA, CI group), murine interferon-gamma (IFN
      gamma) plus lipopolysaccharide (LPS) (T group), IFN-gamma plus LPS and LNMMA (TI
      group), or the same volume of culture medium (C group). The transcriptional
      levels of isocitrate lyase were detected using real-time RT-PCR, and its
      expression levels detected biochemically. RESULTS: The transcriptional levels of
      isocitrate lyase in C, CI, T, TI groups were 1.00, 1.42, 33.09, and 74.88
      (P<0.05), while the expression levels were 0.06, 0.07, 0.18, and 0.93,
      respectively (P<0.05). The content of nitric oxide in T group was significantly
      higher than that in the other groups (P<0.01), but the CFU of T group was the
      lowest (P<0.01). CONCLUSION: Reactive nitrogen intermediates induced by
      stimulated murine macrophages restrain the expression of isocitrate lyase of
      Penicillium marneffei and development of Penicillium marneffei, in which process
      the glyoxylate pathway may play an important role.

PMID- 17545075
TI  - [Developmental changes in synaptic and extrasynaptic N-methyl-D-aspartate
      receptors in cultured rat hippocampal neurons].
AB  - OBJECTIVE: To investigate changes in synaptic and extrasynaptic N-methyl-D
      aspartate receptors (NMDAR) during the development of cultured rat hippocampal
      neurons. METHODS: Synaptic and extrasynaptic NMDAR channel currents were recorded
      from 1-day-old rat hippocampal neurons cultured for 1 and 2 weeks with patch
      clamp technique in whole-cell configuration and outside-out configuration,
      respectively. RESULTS: The amplitude of NMDAR-mediated miniature excited
      postsynaptic current (Meps(CNMDA)) decreased in neurons cultured for 2 weeks as
      compared with that recorded in neurons cultured for 1 week, and the 2-week
      neurons showed also much lowered sensitivity to selective NR2B blocker
      ifenprodil. The amplitude and open probability of extrasynaptic NMDAR in the 2
      week neurons were significantly higher than those in the 1-week neurons, but the
      neurons differred little in conduction and reverse potential. Ifenprodil
      decreased the high conductance and open probability in both neurons, but the
      effect was more potent in the 2-week ones. CONCLUSIONS: There can be
      developmental changes in synaptic and extrasynaptic NMDAR channel currents in
      cultured rat hippocampal neurons, indicating that different NMDAR subtypes are
      expressed in the synaptic and extrasynaptic regions during the development of the
      hippocampal neurons. In 1-week neurons, NR2B are predominant both in synaptic and
      extrasynaptic regions, and at 2 weeks, synaptic NR2B are replaced by NR2A but
      NR2B still remains the predominant subtypes outside the synapses.

PMID- 17545076
TI  - [Recombinant prokaryotic plasmid construction and high expression of FUS1 gene].
AB  - OBJECTIVE: To construct the prokaryotic plasmid of FUS1 gene for efficient FUS1
      expression in E.coli strain Rosetta(DE3)2plys. METHODS: The full-length FUS1 gene
      was amplified by PCR from the total RNA of umbilical mesenchymal stem cells and
      cloned into pET-32a(+) vector followed by identification with PCR and sequencing.
      The recombinant plasmid pET-32a(+)-FUS1 was transformed into the E.coli strain
      Rosetta(DE3)2plys and the target protein expression was induced by IPTG. RESULTS:
      The plasmid pET-32a(+)-FUS1 was obtained successfully as verified by PCR and
      sequence analysis. High expression of the fused FUS1 protein was achieved after
      induction by low-concentration IPTG (25 micromol/L) for 3 h, and the recombinant
      FUS1 protein accounted for 40% of the total bacterial protein of
      Rosetta(DE3)2plys. CONCLUSION: The recombinant FUS1 plasmid has been successfully
      cloned, which allows highly efficient FUS1 expression in Rosetta (DE3)2 plys.

PMID- 17545077
TI  - [Cloning of human PRL-3 gene and construction of its prokaryotic expression
      vector].
AB  - OBJECTIVE: To obtain the entire coding sequence of human PRL-3 gene and construct
      its prokaryotic expression vector. METHODS: With total RNA extracted from the
      human colorectal carcinoma cell line SW480 as the template, PRL-3 gene was
      amplified by RT-PCR with primers designed according to the published sequence of
      GenBank, and the product was inserted into pGEM-T Easy vector. The recombinant
      plasmid pGEM-T-PRL-3 was identified by restriction endonuclease analysis and DNA
      sequencing. After digestion with restriction endonuclease, PRL-3 gene was cloned
      into the multicloning sites of the prokaryotic expression vector pGEX-4T-1.
      RESULTS AND CONCLUSION: The entire coding region of human PRL-3 gene was cloned,
      and the recombinant pGEX-4T-1-PRL-3 vector was successfully constructed and
      expressed, which may provide the basis for further study of the relationship
      between human colorectal carcinoma and PRL-3 gene.

PMID- 17545078
TI  - [Phase IIa clinical trail of hemocoagulase acutus for injection].
AB  - OBJECTIVE: To evaluate the efficacy and safety of hemocoagulase acutus for
      injection and determine its curative dose. METHODS: Forty-five patients on
      abdominal surgeries were randomly allocated into 2 study groups and 1 control
      group. Thirty minutes before the operation, the patients in the study groups
      received intravenous hemocoagulase acutus at 1 U and 2 U, respectively, and
      control group had no treatment. The hemostatic time, hemorrhagic volume, and
      hemoagglutination were observed in all the groups. RESULTS: The average
      hemorrhagic volume and hemorrhagic volume per square were significantly lower in
      the two study groups than in the control group (P<0.05), and the average
      hemorrhagic volume per square were significantly lower in study group 2 U than in
      the 1 U group (P<0.05). No significant differences were found in adverse effects
      between the 3 groups. CONCLUSION: Hemocoagulase acutus for injection has good
      hemostatic effect for controlling capillary hemorrhage at the abdominal incisions
      and can be safely used in the surgical patients.

PMID- 17545079
TI  - [Avastin combined with cisplan inhibits malignant ascites production in nude mice
      bearing transplanted ovary carcinoma with high VEGF expression].
AB  - OBJECTIVE: To establish a nude mouse model of malignant ascites with human
      ovarian carcinoma cell line OVCAR3 which highly expresses VEGF and evaluate the
      therapeutic of Avastin combined with cisplan. METHODS: Forty-eight nude mice with
      malignant ascites resulting from intraperitoneal transplantation of human ovarian
      carcinoma cell line OVCAR3 were treated with intraperitoneal injection of
      Avastin, cisplan, their combination, and PBS, respectively, to observe the effect
      on ascites development, VEGF content in the ascites, peritoneal permeability,
      development of new vessels and number of tumor cells in the ascites. RESULTS:
      Avastin obviously inhibited ascites accumulation and peritoneal capillary
      permeability, reduced VEGF protein level and microvascular density in the tumor
      tissues and the number of red cells and tumor cells in the malignant ascites, and
      prolonged the survival of the mice. The combination of Avastin and cisplan
      further enhanced the therapeutic efficacy of Avastin. CONCLUSION: The bio
      chemotherapeutic strategy with Avastin combined with cisplan can be a promising
      method for treatment of malignant ascites.

PMID- 17545080
TI  - [Cromolyn sodium ameliorates rat left cardiac function during intestinal ischemia
      reperfusion].
AB  - OBJECTIVE: To investigate cardiac function impairment and myocardial injury in
      rats with intestinal ischemia-reperfusion and the protective effect of cromolyn
      sodium. METHODS: Thirty-two SD rats were randomized into 4 groups (n=8), namely
      the sham operation group, model group, 50 mg/kg cromolyn sodium group, and 25
      mg/kg cromolyn sodium group. Intestinal damage was induced by clamping the
      superior mesenteric artery for 45 min followed by reperfusion for 60 min.
      Cromolyn Sodium was administrated intaperitoneally 15 min before reperfusion. The
      heart rate (HR), left ventricle pressure (LVSP), and the maximal/minimum rate of
      LVSP (+dp/dt(max), -dp/dt(max)) were sacrificed immediately before ischemia
      (baseline, T(0)), at 15 min (T(1)), 30 min (T(2)), 45 min (T(3)) of ischemia, and
      at 3 min (T(4)), 5 min (T(5)), 10 min (T(6)), 15 min (T(7)), 45 min (T(8)), 60
      min (T(9)) of reperfusion. At the end of the experiment, the rats were executed
      and the hearts were immediately removed for observation of the pathological
      changes and determination of MDA contents and SOD activity. RESULTS: Compared
      with the baseline T(0), the HR, +dp/dt(max), -dp/dt(max) and the LVSP were
      decreased significantly at T(8) and T(9) in the model group and the two cromolyn
      sodium groups (P<0.05). Compared with the sham operation group, these indices
      were also significantly decreased at T(8) and T(9) in the model group and the two
      cromolyn sodium groups, but the model group had significantly lower levels for
      these indices at T(8) and T(9) than the two cromolyn sodium groups (P<0.05). The
      score of myocardial injury in the model group and the two cromolyn sodium groups
      were significantly higher than that of group A, and 50 mg/kg cromolyn sodium
      group had lower score than the model group (P<0.05). The rats in the model group
      had significantly higher MDA levels than those in the sham operation group and
      the 50 mg/kg cromolyn sodium group. SOD activities in the model group and 25
      mg/kg cromolyn sodium group was lower than that in the sham operation group
      (P<0.05), but 50 mg/kg cromolyn sodium group had significantly higher SOD
      activities than the model group (P<0.05). CONCLUSION: Cromolyn sodium can protect
      the myocardium against intestal ischemia-reperfusion injury and improve the
      cardiac function.

PMID- 17545081
TI  - [Construction of eukaryotic expression vector for VEGF165 gene and its expression
      in rat bladder smooth muscle cells].
AB  - OBJECTIVE: To construct an eukaryotic expression vector for vascular endothelial
      growth factor (VEGF) 165 gene and obtain VEGF expression in rat bladder smooth
      muscle cells. METHODS: VEGF165 cDNA was cloned into the eukaryotic expression
      vector pcDNA3.1(-), and the resultant recombinant vector pcDNA3.1(-)/VEGF165 was
      transfected into the rat bladder smooth muscle cells by electroporation. VEGF
      expression in the cells was determined by RT-PCR and immunofluoresence assay, and
      the biological activity of VEGF in the supernant of the transinfected cell
      culture was tested by MTT assay. RESULTS AND CONCLUSION: VEGF expression was
      obtained in the transinfected cells, and the supernant of the transinfected cell
      cultures stimulated the proliferation of the endothelial cells.

PMID- 17545082
TI  - [Treatment of recurrent condyloma acuminatum with solid lipid nanoparticle gel
      containing podophyllotoxin: a randomized double-blinded, controlled clinical
      trial].
AB  - OBJECTIVE: To observe the clinical efficacy and safety of podophyllotoxin
      delivered via solid lipid nanoparticle gel for topic treatment of recurrent
      condyloma acuminatum. METHODS: In a randomized double-blinded study,
      podophyllotoxin solid lipid nanoparticles gel and routine podophyllotoxin gel
      preparation was applied respectively for treatment of 97 volunteer patients with
      recurrent condyloma acuminatum. The therapeutic effect, condyloma acuminatum
      relapse following the treatment and adverse effect were evaluated. RESULTS: The
      wart clearance rate in the condyloma acuminatum patients in the first treatment
      course with podophyllotoxin solid lipid nanoparticle gel reached 97.1%, close to
      that with the routine preparation of 90.6%, but the nanoparticle preparation
      significantly reduced the recurrence rate and adverse effect (P<0.01).
      CONCLUSION: Podophyllotoxin delivered via solid lipid nanoparticle gel can
      effectively clear condyloma acuminatum and reduce its recurrence rate with only
      mild, tolerable adverse effect.

PMID- 17545083
TI  - [Evaluation of ultramicroporous expanded polytetrafluoroethylene mitral valve
      under pulsatile flow condition in vitro].
AB  - OBJECTIVE: To test 25# and 27# ultramicroporous expanded polytetrafluo-roethylene
      mitral valve (UPMV) under pulsatile flow condition in vitro. METHODS: Six 25# and
      six 27#UPMV were tested using TH-1200 HV Prosthesis Pulsatile Flow Tester in
      vitro at the cycling rate of 70 cycle/min, with the systolic pressure maintained
      at about 16 kPa (120 mmHg), diastolic pressure at 10.7 kPa (80 mmHg), and the
      percentage of mean forward flow at 35%. The stimulant cardiac output was
      maintained at 2, 3, 4, 5 and 6 L/min, respectively, for the testing. RESULTS: The
      mean pressure difference for the 25#UPMV under stimulant cardiac output of 2, 3,
      4, 5 and 6 L/min was 2.488-/+0.378, 4.427-/+0.240, 5.460-/+0.449, 6.776-/+0.391
      and 8.327-/+0.490 mmHg, and its effective valvular orifice was 1.430-/+0.333,
      1.993-/+0.208, 2.260-/+0.477, 3.204-/+0.174 and 3.652-/+0.158 cm(2),
      respectively. The regurgitant fraction of the 25#UPMV under each stimulant
      cardiac output was (5.731-/+0.643) %, (5.431-/+0.312) %, (5.059-/+0.708) %,
      (3.545-/+0.097) % and (2.615-/+0.125) %, respectively. The mean pressure
      difference of the 27#UPMV under each stimulant cardiac output was 1.618-/+0.497,
      3.448-/+0.440, 4.825-/+0.434, 5.494-/+0.446 and 7.482-/+0.455 mmHg, effective
      valvular orifice was 1.773-/+0.364, 2.113-/+0.305, 2.409-/+0.295, 3.326-/+0.417
      and 4.522-/+0.445 cm(2), and regurgitant fraction was (5.357-/+0.509) %, (5.407
      /+0.110) %, (4.999-/+0.182) %, (4.010-/+0.254) % and (2.584-/+0.114)%,
      respectively. CONCLUSION: The mean pressure difference, effective valvular
      orifice and regurgitant fraction of the UPMVs can measure up to the national
      criteria for artificial heart valve prosthesis of China.

PMID- 17545084
TI  - [Biological activity of survivin antisense oligonucleotide labeled with quantum
      dots or green fluorescein: a comparative study].
AB  - OBJECTIVE: To compare the durability of quantum dots with that of green
      fluorescein for labeling survivin antisense oligonucleotide (ASODN) and
      investigate the difference in growth and apoptosis of cells transfected with the
      labeled survivin ASODN. METHODS: Survivin ASODN labeled with quantum dots or
      green fluorescein was transfected into MCF-7 cells via Lipolifectmain(TM2000).
      The proliferation of MCF-7 cells was assessed with MTT assay, survivin mRNA
      expression determined by RT-PCR and its protein expression measured by Western
      blot analysis. The apoptosis rate of the transfected cells was estimated by flow
      cytometry, and the fluorescence distribution in the cells observed under
      fluorescent inverted microscope. RESULTS: The mRNA and protein expressions of
      survivin were significantly decreased in the MCF-7 cells after cell transfection
      with survivin ASODN labeled with quantum dots or green fluorescein, and no
      significant difference was noted between the two labeling methods (P>0.05). Nor
      did survivin ASODN transfection with different labeling methods produced
      significant difference in cell proliferation and apoptotic rate (P>0.05). For
      green fiuorescein labeling, the fluorescence disappeared 4 days after
      transfection, whereas the fluorescence sustained for 1 week for quantum dots
      labeling. CONCLUSION: Survivin ASODNs labeled with quantum dots and green
      fiuorescein do not significantly differ in survivin expression or the transfected
      cell proliferation and apoptosis rate, but quantum dot labeling can be more
      stable with longer maintcnance of the labeling.

PMID- 17545085
TI  - [Triptolide-eluting stent prevents porcine coronary artery in-stent restenosis by
      affecting PCNA and P27(kip1) expression].
AB  - OBJECTIVE: To investigate the effectiveness and safety of triptolide-eluting
      stents implanted in porcine coronary arteries for restenosis prevention, and its
      effect on the expression of proliferating cell nuclear antigen (PCNA) and
      P27(kip1). METHODS: Ten triptolide-eluting stents and 10 stainless steel stents
      (control) were implanted in 20 porcine coronary arteries at random. Four weeks
      later, angiography of the arteries was performed along with also
      histopathological and immunochemical examinations. RESULTS: The in-stent minimal
      lumen diameter of triptolide group was significantly greater, and the neointimal
      area significantly smaller, than those of the control group (P<0.05). PCNA
      expression was significantly lower while P27(kip1) protein significantly higher
      in triptolide group than in the control group (P<0.05). CONCLUSION: Triptolide
      eluting stent can effectively inhibit neointimal formation to prevent restenosis
      in porcine coronary artery 4 weeks after implantation, probably by inhibiting
      P27(kip1) expression and consequently vascular smooth muscle cell proliferation.

PMID- 17545086
TI  - [Identification of a novel candidate gene KLRC1 within the putative
      susceptibility locus for systemic lupus erythematosus at 12p12.3-13.2 in a
      Chinese cohort].
AB  - OBJECTIVE: To identify the candidate genes within the putative susceptibility
      locus for systemic lupus erythematosus (SLE) at 12p12.3-13.2. METHODS: KLRC1 was
      selected as the candidate gene according to the results of previous gene chip
      studies. TaqMan real-time quantitative PCR was performed for detecting KLRC1 mRNA
      expression in 55 SLE patients and 30 controls. RESULTS AND CONCLUSION: KLRC1 mRNA
      expression was significantly higher in the mononuclear cells and T cells of SLE
      patients than in the healthy controls (P<0.01), but showed no significant
      difference in the B cells. No obvious correlation was found between the SLE
      disease activity index (SLEDAI) and KLRC1expression level, suggesting that KLRC1
      can be a probable candidate gene for SLE on 12p12.3-13.2, but which is not
      associated with the disease activity.

PMID- 17545087
TI  - [Safety evaluation of iodine-125 seed implantation in rabbit liver tissue].
AB  - OBJECTIVE: To evaluate the safety of iodine-125 seed implantation in the liver.
      METHODS: Twenty New Zealand rabbits were divided into control and treatment
      groups and in the latter, iodine-125 seeds of 37 MBq were implanted into the
      liver under CT guidance whereas nonradioactive seeds were implanted in the
      control rabbits. Four weeks after implantation, white blood cell count, liver
      functions, and renal functions were measured or evaluated for comparison with
      those before implantation. The rabbits were then anesthetized to collect the
      liver tissue for pathological examination with HE staining and cell apoptosis
      assay. RESULTS: Obvious hepatic tissue necrosis was observed around the
      radioactive seeds in the treatment group. At a 5 mm distance to the seeds, a
      distinct boundary occurred between the necrotic hepatic cells and normal cells.
      The control rabbits, however, had normal liver structure around the seeds
      implanted. In situ cell apoptosis examination showed a distinct band of apoptotic
      cells in the liver tissue of rabbits in the treatment group, which was not found
      in the control group. Two weeks after iodine-125 irradiation, alanine
      aminotransferase significantly increased in the treatment group (t=6.285,
      P<0.001), but recovered two weeks later (t=2.002, P=0.06). No significant
      alterations occurred in aspartate aminotransferase, blood urea nitrogen, serum
      creatinine, hemoglobin, serum total bilirubin, white blood cell count, or
      platelet count after the seed implantation. CONCLUSION: Iodine-125 seed
      implantation in the liver results in conformal irradiation dose distribution
      without obvious effects on the vital organs, demonstrating iodine-125 seed
      implantation as a safe and minimally invasive technique for hepatic cancer
      treatment.

PMID- 17545088
TI  - [Tubeimoside I-induced ultrastructural changes of human cervical carcinoma HeLa
      cell line and the protective effect of cyclosporine A].
AB  - OBJECTIVE: To observe the ultrastructural changes of HeLa cells in response to
      tubeimoside I (TBMS1) treatment and the protective effect of cyclosporine A
      (CsA), and explore the role of intrinsic apoptosis pathway in TBMS1-induced HeLa
      cell apoptosis. METHODS: HeLa cells were treated with TBMS1 (10-50 micromo/L)
      alone or in combination with 2 micromol/L CsA for 12 and 24 h and observed with
      transmission electron microscope (TEM) for the ultrastructural changes of the
      cells. RESULTS: TBMS1 induced apoptosis of HeLa cells in a concentration- and
      time-dependant manner. Under TEM, the treated cells progressively shrunk and the
      intercellular space widened with loss of microvillus, mitochondrial swelling,
      rough endoplasmic reticulum enlargement, chromatin condensation, nuclear
      shrinkage and nuclear pyknosis as TBMS1 concentration increased. At low
      concentrations, CsA offered partial protection of the mitochondria from TBMS1
      induced damage whereas high-concentration CsA did not. CONCLUSION: TBMS1 induces
      ultrastructural changes typical for apoptosis of the HeLa cells, which provides
      morphological evidence for the role of intrinsic apoptosis pathway in TBMS1
      induced apoptosis.

PMID- 17545089
TI  - [Therapeutic effect of Ginkgo biloba leaf extract on hypercholestrolemia in
      children with nephrotic syndrome].
AB  - OBJECTIVE: To explore the therapeutic effects of the extract of Ginkgo biloba
      leaf on hypercholestrolemia in children with primary nephritic syndrome (NS).
      METHODS: Thirty-five children with NS were randomized into 2 groups for treatment
      with prednisone plus Ginkgo biloba leaf extract (18 cases) or with prednisone
      plus dipyridamole (17 cases) for 8 weeks. After completion of the treatments, the
      therapeutic effects were evaluated and the changes in the blood biochemical
      markers assayed. RESULTS: The 8-week treatment with the extract significantly
      ameliorated the clinical symptoms and blood biochemistry as compared with
      prednisone plus dipyridamole group (P<0.01). The levels of urinic protein and
      blood lipid in Ginkgo leaf group were significantly lower than those in
      prednisome plus dipyridamole group (P<0.05). CONCLUSION: The extract from Ginkgo
      biloba leaf can lower blood lipid levels and urinic protein in children with NS
      and improve their clinical syptoms and the renal function, therefore has much
      clinical value as an adjuvant treatment of steroid therapy in such children.

PMID- 17545090
TI  - [Time window for intubation after rocuronium administration during target
      controlled infusion of propofol and sulfentanil].
AB  - OBJECTIVE: To define the ideal time window for intubation after rocuronium
      administration during target-controlled infusion (TCI) ofpropofol and
      sulfentanil. METHODS: One hundred and twenty elective surgical patients (age
      range 18-55 years) were randomized into 4 groups (n=30) according to the
      intubation time after administration of the muscle relaxant. Patients with
      predicted difficult airway were excluded. General anesthesia was induced by TCI
      of propofol and sulfentanil. A senior anesthesiologist blinded for the
      randomization performed the intubations at 1, 2, 3, or 4 min after injection of
      rocuronium, and the vocal card visibility was evaluated upon full exposure of the
      vocal cord and the intubation conditions assessed according to Cooper's score.
      RESULTS: The intubation conditions were excellent or good in all patients, but
      the vocal cord visibility at 2-4 min differed significantly from that at 1 min
      after rocuronium administration (P<0.01). Suppression of the neuromuscular
      function 1 min after rocuronium administration differed significantly from that
      at other time points (P<0.01). CONCLUSION: The condition of vocal cord can be
      more suitable for intubation at 2-4 min than at 1 min after rocuronium
      administration as the ideal time window for intubation during TCI of propofol and
      sulfentanil.

PMID- 17545091
TI  - [Protective effect of Yigan Fuzheng Paidu capsules combined with ozone on CCl4
      induced acute hepatic injury in dogs].
AB  - OBJECTIVE: To investigate the protective effect of Yigan Fuzheng Paidu Capsules
      (YC) combined with medical ozone against hepatic injury in dogs induced by
      hepatotoxic drug. METHODS: Twenty-four dogs were randomized equally into 4 groups
      (n=6), namely the model group, oleanolic acid tablet (OAT) group, YC group and
      YC+O(3) group, given either no particular treatment, oral OAT at 10 mg/day, oral
      YC at 0.2 g/day, or YC at 0.2 g/day plus 150 ml medical ozone transrectal
      insufflation every other day, respectively, for totally 30 consecutive days.
      Acute hepatic injury was induced after the treatment in the dogs with a sing-dose
      intraperitoneal injection of 0.9 ml/kg CCl(4) and peanut oil mixture (1:1, W/W).
      The general condition, survival time, alanine aminotransferase (ALT), aspartate
      aminotransferase/alanine aminotransferase (AST/ALT), serum total bilirubin
      (TBIL), prothrombin time (PT), blood ammonia (AMMO), and blood urea nitrogen
      (BUN) were recorded or measured. The hepatic pathological changes were observed
      upon death or on day 15 following CCl(4) injection. RESULTS: Compared with the
      other 3 treatment protocols, YC plus O(3) showed favorable effects on the
      activity, mental state, diet, urination and defecation of the dogs, which had
      significantly higher survival rate and higher levels of ALT, TBIL, PT, and AMMO
      than the model and OAT groups (P<0.05). AST/ALT remained normal in YC+O(3) group,
      which had also milder hepatic injury than the other 3 groups. CONCLUSIONS: YC
      combined with medical ozone may decrease transaminase and blood ammonia levels,
      relieve jaundice, prolong the survival time of dogs with CCl(4)-induced hepatic
      injury.

PMID- 17545092
TI  - [Association of CD133 and endothelin-converting enzyme expressions with prognosis
      of non-small cell lung carcinoma].
AB  - OBJECTIVE: To investigate the expression of tumor stem cell marker CD133 and
      endothelin-converting enzymes (ECE) in non-small cell lung carcinoma (NSCLC) and
      their association with NSCLC lymphoid metastasis. METHODS: CD133 and ECE
      expressions was detected immunohistochemically in the specimens from 77 patients
      with NSCLC, and the association of CD133 and ECE expressions with the tumor size,
      histological type, differentiation, lymphoid metastasis, and prognosis of NSCLC
      was analyzed. RESULTS: The positive expression rate of CD133 and ECE was 51.9%
      (40/77) and 45.5% (35/77) in these specimens, respectively. Both CD133 and ECE
      expressions were associated positively with lymphoid metastasis (r=0.246 and
      0.339, P<0.05), and inversely with the survival time of the patients (P<0.05).
      CD133 and ECE expressions were not related to tumor size, histological type, and
      differentiation of the tumor (P>0.05). CD133 expression was associated positively
      with ECE expression in NSCLC (r=0.249, P<0.05). CONCLUSION: CD133 and ECE
      expressions are associated with lymphoid metastasis and prognosis of NSCLC, and
      their overexpression often suggests unfavorable prognosis of NSCLC.

PMID- 17545093
TI  - [Expression of aquaporins 1, 3, 8, 9 mRNA in human fetal membranes].
AB  - OBJECTIVE: To investigate the expression of aquaporin (AQP)-1, 3, 8, 9 in human
      fetal membrane and their role in the human amniotic fluid circulation. METHODS:
      RT-PCR was employed for detection of the expressions of AQP-1, 3, 8, 9 mRNA in
      human amnion and chorion from 20 women with normal term pregnancy. RESULTS: AQP
      1, 3, 8, 9 mRNA expression was detected in both human amnion and chorion, and no
      significant difference was found in their expression levels or between the amnion
      and chorion (P>0.05). CONCLUSION: AQP-1, 3, 8, 9 can be associated with
      intramembranous transport and volume regulation of amniotic fluid.

PMID- 17545094
TI  - [Ultrastrtctural observation of bone marrow stromal cells cultured in coralline
      hydroxyapatite].
AB  - OBJECTIVE: To observe the ultrastructure of bone marrow stromal cells (BMSCs)
      cultured in coralline hydroxyapatite (CHA) and evaluate their biocompatibility.
      METHODS: BMSCs isolated from dogs were cultured with CHA as the scaffold, and the
      morphologies of the cells were observed with phase-contrast microscope and
      scanning electron microscope. RESULTS AND CONCLUSION: BMSCs grew well with good
      attachment to the CHA scaffold and performed normal function, demonstrating CHA
      as one of useful biocarrier materials for bone tissue engineering.

PMID- 17545095
TI  - [Thermotherapy enhances the sensitivity of lymphoma cell line Raji to
      chemotherapy in vitro].
AB  - OBJECTIVE: To observe the effect of thermotherapy on the intracellular adriamycin
      concentration and apoptosis of Raji cells in vitro. METHODS: The working
      concentration of adriamycin against Raji cells was determined with MTT assay.
      Raji cells were subjected to thermotherapy (at 40 degrees Celsius;, 41 degrees
      Celsius; or 42 degrees Celsius;) and chemotherapy with adriamycin alone or in
      conjunction, and the cell survival rates were determined 48 h after the
      treatment. The cell growth inhibition effect of the treatment was evaluated with
      MTT assay, and the apoptotic rates of Raji cells and alteration of intracellular
      adriamycin concentration were determined by flow cytometry. RESULTS: The IC(50)
      of adriamycin was defined as the working concentration in the experiment.
      Thermotherapy at 40, 41 and 42 degrees Celsius; for 60 min in conjuction with
      chemotherapy significantly inhibited the growth of Raji cells (P<0.01). The
      results of flow cytometry showed that thermotherapy and adriamycin chemotherapy,
      used either alone or in combination, significantly increased the apoptotic rates
      of Raji cells (P<0.01), and thermotherapy remarkably increased the intracellular
      concentration of adriamycin. CONCLUSION: Adriamycin chemotherapy combined
      thermotherapy for 60 min can increase the intracellular concentration of
      adriamycin and the apoptosis rates of Raji cells.

PMID- 17545096
TI  - [Drug sensitivity test and drug-resistance gene assessment for chemotherapy
      planning for tumors derived from high-passage mouse gastric cancer cells:
      therapeutic effect observation in mice].
AB  - OBJECTIVE: To study the effect of chemotherapy with drugs selected according to
      drug sensitivity test and drug- resistance gene assessment in mice bearing tumors
      derived from high-passage gastric cancer cells. METHODS: Chemosensitivity of the
      mouse gastric cancer cells to 6 chemotherapeutic drugs was investigated using MTT
      assay before the 6 drugs were applied in mice with implanted tumors. The
      implanted tumor volume and tumor inhibition rate were observed, and the
      expression of the multidrug resistance-1 (MDR1) gene was detected. RESULTS: 5-FU,
      the most sensitive among the 6 drugs, resulted in significantly higher tumor
      inhibition rates in comparison with the control group, but did not significant
      affect MDR1 expression. Adriamycin (ADM) had the lowest sensitivity with low
      tumor inhibition rates and no significant effect on MDR1 expression. Cisplatin
      (DDP) was identified as the most sensitive drug for mouse gastric cancer with
      previous 5-FU exposure, and Mitomycin (MMC) was the most insensitive drug for
      mouse gastric cancer with previous ADM treatment. In mice bearing tumors of the
      second-passage cells, DDP showed high tumor inhibition rate but scarcely affected
      MDR1 expression; MMC resulted in low tumor inhibition rate and high MDR1
      expression. Application of 5-FU and ADM in these tumor-bearing mice of the second
      passage cancer cells resulted in rather low tumor inhibition rates without
      significant alterations in MDR1 expression as compared with the control group.
      CONCLUSION: Appropriate individualized chemotherapy should be implemented in full
      consideration of the results of drug sensitivity test and drug-resistance gene
      assessment.

PMID- 17545097
TI  - [CT perfusion study of acute local cerebral infarction in rhesus monkeys].
AB  - OBJECTIVE: To explore the value of CT perfusion in early diagnosis and management
      of superacute local cerebral infarction in rhesus monkeys. METHOD: Acute local
      cerebral infarction was induced in the rhesus monkeys during digital subtraction
      angiography (DSA) by introduction of pale thrombus prepared from autologous blood
      into the M1 branch of the middle cerebral artery (MCA). Plain CT scan and CT
      perfusion scanning were performed at different time points before and after DSA
      operation, and the results were analyzed in conjunction with the pathologic
      changes. RESULTS: Ischemic lesions were displayed on CT perfusion images, which
      showed local hypoperfusion, reduced cerebral blood flow and volume, and mean
      transit time delay in the compromised area. Local hypointense infarct area was
      identified in plain CT scan 24 h after the DSA operation, and the results were in
      good agreement with pathological examination during autopsy. CONCLUSION: CT
      perfusion imaging of the brain can accurately capture the cerebral perfusion
      deficits in acute ischemic stroke before morphologic changes take place, and
      therefore provides good means for thrombolytic treatment evaluation of stroke.

PMID- 17545098
TI  - [Audiological assessment in 79 patients with tympanosclerosis].
AB  - OBJECTIVE: To conduct audiological assessment in patients with tympanosclerosis.
      METHODS: A retrospective review was conducted in 79 patients with
      tympanosclerosis (involving 79 ears) with complete records, including 30 patients
      (30 ears) with fixed Malleus-incus complex, 29 (29 ears) with fixed stapes, and
      20 (20 ears) with fixations of both the stapes footplate and the Malleus-incus
      complex. Audiometry was performed for all the patients one or two days before
      operation, and the audiological features of the patients were compared between
      the 3 groups. RESULTS: Most of the patients (65.8%) suffered conductive hearing
      loss, 32.9% had mixed deafness, and one patient had sensorineural hearing loss.
      No statistically significant differences was noted in the speech frequency (0.5,
      1, and 2 kHz) air conduction pure tone average (PTA) or the air-bone gap (ABG) in
      the 3 groups (P<0.05). CONCLUSION: Most of the patients with tympanosclerosis
      suffer conductive hearing loss, and the severity of hearing loss is not
      associated with the site of tympanosclerosis.

PMID- 17545099
TI  - Effects of Saussurea lappa roots extract in ethanol on leukocyte phagocytic
      activity, lymphocyte proliferation and interferon-gamma (IFN-gamma).
AB  - Effects of Saussurea lappa root extracts prepared in ethanol according to the
      homeopathic principles were assessed on leukocyte phagocytic activity, lymphocyte
      transformation and mitogen-induced interferon-gamma (IFN-gamma) in the cultures
      of peripheral blood mononuclear cells of goats (PBMC) in vitro. Leukocyte
      phagocytic activity was measured by flow cytometry, lymphocyte proliferation by
      MTT and IFN-gamma level in cell culture supernatants was determined by ELISA. The
      results obtained demonstrated that all test dilutions (D4, D6, D8) of Saussurea
      lappa in ethanol have exerted a stimulating effect on leukocyte phagocytic
      activity in dose-dependent manner. A 10 microl dose of Saussurea lappa of each
      dilution markedly enhanced phagocytic activity, while other doses tested made
      only a feeble stimulating effect. The increases with 10 microl dose were found
      significantly (P<0.01) different between each dilution, maximal stimulation was
      observed by D8 dilution. Different doses (10 microl, 2 microl, 1 microl, 0.5
      microl) of all test dilutions (D4, D6, D8) of Saussurea lappa in sterile 0.9%
      NaCl solution inhibited lymphocyte proliferation. Maximal inhibitory effect was
      observed with the 2 microl dose. Similarly, Saussurea lappa suppressed the
      secretion of IFN-gamma by mitogen-activated (PHA; 2.5 microg/ml) of peripheral
      mononuclear cells in dose-dependent manner. In conclusion these findings suggest
      that enhanced leukocyte phagocytic activity may be helpful to clear the soluble
      immune complexes produced during a sustained immune response against self
      antigens which causes chronic inflammatory injury of tissue. On the other hand,
      inhibition of lymphocyte proliferation and IFN-gamma by Saussurea lappa may
      contribute to suppress immune-mediated inflammatory reactions possibly through a
      cell-mediated cytokine pathway. Thus it is concievable that ethanolic extracts of
      Saussurea lappa roots in homeopathetic dilutions may be considered as a potential
      candidate for therapeutic support in autoimmune and chronic inflammatory
      disorders.

PMID- 17545100
TI  - Cephradine antacids interaction studies.
AB  - The present work comprises of interaction studies of cephradine with antacids.
      Cephradine is included among the first generation cephalosporin, which is active
      against a wide range of Gram positive and Gram-negative bacteria including
      penicillinase-producing staphylococci. Since the presence of complexing ligand
      may affect the bioavailability of a drug in blood or tissues, therefore, in order
      to study the probable interaction of cephradine with antacids all the reaction
      conditions were simulated to natural environments. Antacids are commonly used in
      patients complaining of GI irritations. The behavior of cephradine in presence of
      seven antacids i.e., simethicone, magaldrate, magnesium carbonate, magnesium
      hydroxide, magnesium trisilicate, sodium bicarbonate and aluminium hydroxide was
      studied by using standard dissolution apparatus. Cephradine was monitored both by
      UV and by high performance liquid chromatography. The results revealed that
      antacids containing polyvalent cations retarded the in vitro availability of
      cephradine. Moreover, these studies indicated that cephradine was strongly
      adsorbed on antacids; magnesium trisilicate and simeco tablets (powdered)
      exhibited relatively higher adsorption capacities.

PMID- 17545101
TI  - Anti-inflammatory and analgesic alkaloid from Sida cordifolia linn.
AB  - The analgesic and anti-inflammatory activities of a new alkaloid, 1,2,3,9
      tetrahydro-pyrrolo [2,1-b] quinazolin-3-ylamine (compound 1) isolated from Sida
      cordifolia Linn. were investigated in animal models. In the acetic acid induced
      writhing model, the compound 1 showed 25.4 (P<0.05) and 52.43% (P<0.01)
      inhibition of writhing response at doses of 25 and 50 mg/kg body weight
      respectively. The alkaloid also produced significant increase in the tail flick
      latency in radiant heat tail-flick method. In Carrageenan induced rat paw edema
      the compound 1 produced 16.93 and 24.43 % inhibition of paw edema at the doses of
      25 and 50 mg/kg body weight respectively at the third hour of study.

PMID- 17545102
TI  - Neurochemical and behavioral effects of m-CPP in a rat model of tardive
      dyskinesia.
AB  - Present study was designed to monitor the responsiveness of 5HT (5
      Hydroxytryptamine) -2C receptors following the long-term administration of
      haloperidol in rats. Effects of m-CPP (meta-Chlorophenyl piperazine) were
      monitored 48 h after withdrawal from repeated (twice a day for 5 week)
      administration of haloperidol (at the dose of 1 mg/kg). Vacuous chewing movements
      (VCMs) were monitored on weekly basis. Two days after withdrawal, animals were
      injected with saline (1 ml/kg of body weight) or m-CPP (3 mg/kg of body weight).
      Activities in open field and light dark activity box were monitored 15 and 30 min
      post injection respectively. Animals were then decapitated (4 h post injection)
      to collect dorsal striatum (DS) samples for the neurochemical analysis by HPLC-EC
      (High Performance Liquid Chromatography with Electrochemical detection) method.
      Results from the present study showed significant hypolocomotive effect of m-CPP
      (p<0.05) in both repeated haloperidol as well as repeated saline injected rats.
      Neurochemical analysis of DS by HPLC-EC method showed that administration of m
      CPP significantly (p<0.05) decreased 5-HIAA (5-Hydroxyindol acetic acid) in
      repeated haloperidol injected rats. In conclusion, present study provides
      evidence that 5HT-2C receptors become hypersensitive in a rat model of Tardive
      Dyskinesia (TD). These findings have potential implication in the treatment of TD
      and attenuation of EPS induced by typical neuroleptics.

PMID- 17545103
TI  - W-7 (a calmodulin antagonist) inhibits carrageenan-induced paw edema in intact
      and adrenalectomized rats.
AB  - The aim of present study was to investigate the effect of W-7, a calmodulin
      antagonist, on carrageenan-induced rat's paw edema. W-7(50 microMol/kg) was given
      intraperitoneally synchronous with the intraplantar injection of 0.1 ml of 0.5%
      carrageenan solution. After four hours, paw edema was assessed by calculating the
      paw volume changes which measured by hydroplethysmometer. In adrenalectomized
      rats, both adrenal glands were removed. Treatment of animals with W-7 reduced
      carrageenan-induced paw edema by 50%. In adrenalectomized rats, W-7 was also
      effective in reduction of paw edema (52%). There was no significant difference
      between the effect of W-7 in adrenalectomized and control animals. Our findings
      suggest that W-7 as a calmodulin inhibitor reduce carrageenan-induced paw edema
      and the inhibitory effect of W-7 on edema formation appears not to be dependent
      on adrenal function.

PMID- 17545104
TI  - Determination of residues of sulphonamide in eggs and laying hens.
AB  - Eggs were collected from different areas of Faisalabad city. The quantity of
      sulphonamides was determined in yolk, white and whole egg and compared with the
      permissible limit 1 microg/ml for sulphadimethoxine available in literature. In
      another experiment, a group of hens were kept at a poultry farm after medicating
      them with darvisal liquid to see if the residues of sulphonamide pass into the
      eggs of poultry. The period of existence of residues was noted.

PMID- 17545105
TI  - In vitro interaction studies of diltiazem with NSAID's using UV spectrophotometry
      and RP-HPLC techniques.
AB  - Diltiazem (DTZ) is a well-known cardiovascular drug used clinically in the
      treatment of angina pectoris and hypertension. Present paper deals with the in
      vitro availability studies of DTZ in presence of commonly used nonsteroidal anti
      inflammatory drugs (NSAID's) like diclofenac sodium, flurbiprofen, mefenamic acid
      and meloxicam. Simultaneous administration of both types of drugs may alter the
      antihypertensive effect of DTZ. These studies were carried out using BP 2005
      dissolution test apparatus in simulated human body environments at body
      temperature and at elevated temperature in order to study the kinetics and
      energitics of these interactions. Both the drug in each case were analyzed either
      by measuring the absorbance of aliquots on a UV/VIS spectrophotometer, or by RP
      HPLC method. Present study clearly indicated that most of the NSAID's studied
      bind to DTZ forming charge transfer complexes, evident from the high availability
      of DTZ. Hence, concurrent administration of NSAID's with DTZ is not recommended.

PMID- 17545106
TI  - Pattern of adverse drug reactions due to cancer chemotherapy in a tertiary care
      teaching hospital in Nepal.
AB  - Use of cancer chemotherapeutic drugs is associated with several adverse drug
      reactions (ADRs) ranging from mild nausea to fatal myelosuppression. Data
      regarding safety profile of cancer chemotherapy is lacking in Nepal. To study the
      pattern of ADRs caused by cancer chemotherapeutic drugs in Manipal Teaching
      Hospital (MTH), Pokhara, Nepal. Hospitalized patients treated with cancer
      chemotherapy drugs from 1st January to 30th June 2006, was studied
      retrospectively. Necessary information was collected from the patients' hospital
      records. Total 60 patients underwent chemotherapy among which 25 (41.67%)
      developed ADRs. More than half (60 %) were male and 40 % were of age group 61-70
      years. The mean SD age was 57.8 +/- 11.54 years. More than half of the patients
      (56%) who developed ADRs were on adjuvant chemotherapy. Alkylating agents were
      responsible for the ADRs in nearly half of the patients (52%) followed by
      antimetabolites (20%). Cisplatin was the individual drug responsible for 44% of
      the ADRs. The onset of the ADR was within a day in 44% of the patients. Thirty
      six percent of patients developing ADRs stayed in the hospital for 1-4 days.
      Hematological system was affected primarily (40.47% of the patients), followed by
      the gastrointestinal tract (33.33%). Grade I neutropenia was the most common ADR
      affecting 28.6% of the patients, followed by emesis (21.4%). Increased dose of
      antiemetics was needed in 38.5% of the patients to manage the ADRs. Levamisole
      was the drug used primarily (30.43%) for managing ADRs. Male patients and age
      group 61-70 years were highly predisposed to ADRs. Cisplatin was the common drug
      responsible for ADRs. Levamisole was commonly used in managing the ADRs. Similar
      studies covering more patients form different regions are needed to validate our
      findings.

PMID- 17545107
TI  - Improved bioavailability of aceclofenac from spherical agglomerates: development,
      in vitro and preclinical studies.
AB  - The objective of present study was to improve the solubility, dissolution rate,
      micromeritic properties and bioavailability of aceclofenac (NSAID) by formulating
      its spherical agglomerates. They were prepared with different water soluble
      polymers (polyvinylpyrrolidone-K30, polyvinylpyrrolidone-K90 and sodium alginate)
      by using acetone-water-dichloromethane solvent system. The agglomerates were
      subjected to various physicochemical properties, DSC, IR spectroscopy, scanning
      electron microscopy (SEM), micromeritic properties and dissolution studies. The
      in vivo studies (anti-inflammatory, analgesic and pharmacokinetic studies) were
      conducted in Wistar rats and Swiss albino mice. SEM studies showed that
      agglomerates were spherical in structure and formed by cluster of small crystals.
      The agglomerates prepared with polyvinylpyrrolidone-K90 exhibited improved
      solubility, dissolution rate and micromeritic properties compared to those
      prepared with other polymers and pure drug. These optimized agglomerates showed
      rapid analgesic and anti-inflammatory activity besides exhibiting improved
      bioavailability of drug when compared to pure drug.

PMID- 17545108
TI  - Effect of partial replacement of different defatted oil seed cakes as substrate
      in biosynthesis of bacitracin in solid-state fermentation by Bacillus
      licheniformis.
AB  - The present study was conducted to ascertain the effect of partial replacement of
      different defatted oil seed cakes as substrate i.e. sunflower meal, rice hulls
      and soybean meal, in biosynthesis of Bacitracin in Solid-State Fermentation by
      Bacillus licheniformis on laboratory scale. In solid-state fermentation, wheat
      bran, soybean meal, sunflower meal, rice hulls and their different combinations
      were used. The antibiotic activity was determined at various intervals and
      recorded 48 hours gave maximum yield, 4375 i.u/gm when only soybean was used.
      However, maximum titre 4820 i.u / gm of antibiotic were obtained when wheat bran
      and soybean meal was in ratio of 1:3. The raw material for its production is
      readily available and cheap such as soybean meal, sunflower meal and wheat bran.
      Thus development of this technology in our country would result in utilizing our
      own resources in Pakistan.

PMID- 17545109
TI  - Ginger facilitates cholinergic activity possibly due to blockade of muscarinic
      autoreceptors in rat stomach fundus.
AB  - Ginger (Zingiber officinale) is a universally known food plant reputed for its
      medicinal use in gastrointestinal disorders as a prokinetic and laxative. We
      recently showed that 70% aqueous-methanolic extract of ginger (Zo.Cr) exhibits
      prokinetic activity in rats via activation of post-synaptic muscarinic M3
      receptor in rat stomach fundus. In view of the physiological significance of pre
      synaptic muscarinic M1 and M2 autoreceptors, this study was undertaken to further
      look into the possible mode of action of the prokinetic effect of ginger through
      inhibition of pre-synaptic muscarinic receptors. Isolated tissue bath experiments
      were performed with Sprague-Dawley rat stomach fundus strip preparations immersed
      in Kreb's solution at 37 degrees C. Carbachol (CCh) maximum responses (1 microM)
      were obtained in rat stomach fundus. Zo.Cr, given in multiple increasing bolus
      concentrations (0.01-0.1 mg/ml) 10 min prior to administration of CCh,
      potentiated the CCh peak responses showing that it is possibly inhibiting the pre
      synaptic muscarinic receptors. Like wise, increasing bolus concentrations of
      pirenzepine (0.03-0.3 microM) and himbacine (0.01-0.03 microM), standard
      muscarinic M1 and M2 antagonists respectively, also potentiated the CCh
      responses. These results show that ginger, in addition to having a direct
      cholinergic agonistic effect on the post-synaptic M3 receptors, also has a
      possible inhibitory effect on pre-synaptic muscarinic autoreceptors, similar to
      standard muscarinic antagonists, thus reiterating the gastric stimulant effect of
      this age-old plant.

PMID- 17545110
TI  - In vitro availability studies of enoxacin in presence of H2 receptor antagonists.
AB  - Enoxacin is a second-generation quinolone with increased antibacterial activity
      both in potency as well as in terms of broad spectrum against a wide range of
      clinically important pathogens over the first generation quinolones and produces
      its effect by inhibiting bacterial enzyme DNA gyrase. There are a number of drug
      interactions reported for enoxacin. On the other hand H2-receptor antagonists
      block gastric acid secretion and some cardiovascular effects of histamine. As the
      later drugs are used for a long-term therapy, they may be coadministered with
      other drugs. In present study in vitro release of enoxacin in presence of
      cimetidine, ranitidine and famotidine has been studied on a B.P. 2003 dissolution
      test apparatus and compared with the availability of enoxacin and H2-receptor
      antagonists alone. The interacting drugs were analyzed spectrophotometrically.
      These studies were carried out in simulated gastric juice, simulating empty
      stomach, simulated intestinal juice (pH 9) and buffers of pH 7.4 simulating blood
      pH at 37 degrees C. In order to support these interaction studies, the effect of
      H2-receptor antagonists on the antibacterial efficacy (MIC) of enoxacin was also
      studied by turbidity method and compared with parent drug against Staphylococcus
      aureus, Streptococcus pyogens, Streptococcus pneumoniae, Enterococcus,
      Escherichia coli, Salmonella typhi, Pseudomonas aeruginosa, Klebsiella
      pneumoniae, Proteus mirabilis and Bacillus subtilis. On the basis of these
      results, it is suggested that enoxacin should be coadministered with care along
      with H2-receptor antagonists especially in case of ranitidine, although chances
      of adverse reactions are rare but decrease in MIC of enoxacin may result in
      delayed effect or require prolonged use of the drug.

PMID- 17545111
TI  - Can drug utilization help in promoting the more rational use of medicine?
      Experiences from Western Nepal.
AB  - Drug utilization research describes the extent, nature and determinants of drug
      use in populations and aims to facilitate the more rational use of medicines. The
      departments of Pharmacology and Clinical Pharmacy at the Manipal College of
      Medical Sciences, Pokhara, Nepal are committed to promoting the more rational use
      of medicines. The departments run a Drug Information Center and a
      Pharmacovigilance Center in the teaching hospital. Over the last eight years, the
      departments have conducted drug utilization studies in the teaching hospital and
      the community. A few of these were of the intervention type and drug use was
      studied before and after the intervention. Members of the departments are on the
      hospital Drug and Therapeutics Committee. Educational initiatives to improve
      prescribing have been carried out in a few instances. Restricting the number of
      brands in the hospital pharmacy and creation of a hospital drug list has been
      carried out. The impact of these initiatives has been studied only in a few
      cases. Generic prescribing was found to be low. The educational initiatives to
      improve prescribing had only limited success. The hospital is in the process of
      framing antimicrobial use guidelines for various departments. A hospital
      formulary is under preparation. The influence of drug utilization studies on the
      prescribing patterns has been low to moderate. The department of Clinical
      Pharmacy runs a Medication Counseling Center in the hospital and teaches
      appropriate use of medicines to patients. The studies and initiatives to promote
      the more rational use of medicines should be continued and strengthened.

PMID- 17545112
TI  - Spectrophotometric estimation of ambroxol and cetirizine hydrochloride from
      tablet dosage form.
AB  - Fixed dose combination tablets containing ambroxol HCl and cetirizine HCl are
      clinically used as mucolytic and antiallergic. Several spectrophotometric and
      HPLC methods have been reported for simultaneous estimation of these drugs with
      other drugs. The drugs individually and in mixture obeys Beer's law over conc.
      range 1.2-4.4 microg/mL for cetirizine HCL and for ambroxol HCL 15-52 microg/mL
      at all five sampling wavelengths (correlation coeff. well above 0.995). The mean
      recoveries from tablet by standard addition method were 100.18% (+/-2.4) and
      100.66 % (+/-2.31). The present work reports simple, accurate and precise
      spectrophotometric methods for their simultaneous estimation from tablet dosage
      form.

PMID- 17545113
TI  - Fabrication of solid nanoparticles for drug delivery.
AB  - The use of nanoparticles in biotechnology presents a growing interest for the
      numerous possibilities offered by combining the world of materials, with its
      advanced technologies and their diverse properties, and the biological world,
      with its elaborate molecular architectures, properties and functions. Different
      nanoparticles are attractive for their intrinsic properties of optical
      transparency, controllable porosity, chemical inertness and biocompatibility.
      Various synthetic methods have been developed for preparing nanoparticles with
      well-controlled sizes and shapes. Research in nanotechnology and biopharmaceutics
      or collectively nanomedicine has recently taken a new dimension, with amazing
      variety of methods for fabrication of nanoparticles. It is now possible to
      enhance or control drug delivery, this is required in case of poorly soluble
      drug, or drugs to cross blood brain barrier (BBB). Moreover, this technique can
      also be utilized for targeted delivery of drugs. There are number of methods
      reported in literature for the fabrication of nanoparticles. These include Sol
      Gel technique, spraying the drug solution in vacuum, solvent diffusion or
      precipitation method. The former two techniques are mostly used to fabricate
      porous nanoparticles. Present paper reviews these techniques so as to give an
      idea to those planning to start with the fabrication of nanoparticles in a
      particular area of interest.

PMID- 17545114
TI  - [Arterial obliterative disease and physical activity].
AB  - Regular physical exercise represents an essential element in treating patients
      with second-stage peripheral arterial occlusive disease. Peripheral arterial
      occlusive disease is a characteristic clinical manifestation of atherothrombotic
      processes. Its prevalence is 2-3%, consequently, it is estimated to be 200,000
      300,000 patients in Hungary. Coronary artery disease and atherothrombosis of the
      carotid artery system may frequently coexist with peripheral arterial
      obliterative disease. Treatment of peripheral arterial obliterative disease
      influences their prevalence and prognosis as well. The main aim of regular
      physical exercise is to improve the quality of life of patients by increasing the
      functional capacity of the lower limbs. During exercise beneficial vascular
      changes occur like haemodynamic changes consisting of increasing pressure
      gradient of stenotic artery and opening of collateral vessels, as well as
      improvement of the endothelial dysfunction. It favourably influences lipid
      profile by decreasing LDL cholesterol and increasing HDL cholesterol. Physical
      exercise beneficially affects blood rheology as well. It also brings about
      structural changes in the skeletal muscles, increases the enzyme levels in the
      oxidative metabolic processes and enhances the density of capillaries in the
      skeletal muscle fibres. According to the data published so far, patients with
      peripheral arterial obliterative disease are recommended to take part in
      supervised treadmill walking at least 3 days per week for 30-60 minutes each
      session containing 5-5 minute warm-up and cool-down periods. The training should
      be of intermittent intensity at the pain-free threshold. The physiological
      benefits are optimised at 3-6 months. The home-based training programme is also
      remarkably useful.

PMID- 17545115
TI  - [RNA expression as a prognostic tool in idiopathic nephrotic syndrome].
AB  - Approximately 90% of children with nephrotic syndrome have idiopathic nephrotic
      syndrome. Idiopathic nephrotic syndrome includes three histologic types: minimal
      change disease, mesangial proliferation and focal segmental glomerulosclerosis.
      These diseases have similar clinical presentation but different prognosis. The
      aim of this review is to summarize the genetic knowledge related to idiopathic
      nephrotic syndrome, follow the progression of these diseases and to offer a
      survey of the gene expression pattern changes and their functional
      classification. Different types of RNA expression analysis methods, such as the
      northern-blot assay, the ribonuclease protection assay, the RNA in situ
      hybridization, the quantitative RT-PCR and the RNA expression microarray
      technology are discussed. Previous studies emphasize the importance of the
      following gene groups in the idiopathic nephrotic syndrome: genes involved the
      DNA synthesis and repair, growth factors, extracellular matrix proteins,
      extracellular ligand receptors, extracellular signal transduction, metabolic and
      transport process and immune regulation are frequently dys-expressed in
      idiopathic nephrotic syndrome. With the development and spread of the microarray
      technology these genes can be used as a compliment to the conventional diagnostic
      method.

PMID- 17545116
TI  - [Unifying theory of aging].
AB  - Every aging theory intended to find the ultimate cause of aging, however, so far
      all have failed to present the clue as to why aging occurs. Senescence is a
      complex process and the aging hypotheses concentrated on only one or very few
      elements of this process. The goal of the Unifying Theory of Aging is to organize
      these theories into an organic complex. Despite all our hopes aging is
      inevitable, the present information level of the human system allows only a
      temporary existence of an individual in time. During aging the system gradually
      drifts away from the developmentally differentiated state, which results in
      loosing step-by step the capability to cope with the deteriorating entropy force
      of the environment. Nevertheless, it is still possible to increase the mean life
      span of the human population but without altering the present information level
      of the human system aging still remains an incurable disease.

PMID- 17545117
TI  - [Molecular pathology and clinical manifestations of Fabry disease].
AB  - Fabry disease is a rare, progressive lysosomal storage disorder caused by
      mutation in the GAL gene and an impaired function of the alpha-galactosidase A
      enzyme. The enzymatic defect results in the progressive accumulation of
      glycosphingolipids in endothelial cells, smooth muscle cells, leucocytes and
      fibroblasts leading to organ damage in the skin, eye, nervous system, kidney and
      heart. Major clinical manifestations include acroparesthesis, angiokeratoma,
      corneal opacities, vascular diseases of the heart, kidney, and the central
      nervous system. Enzyme replacement therapy has recently become available for the
      treatment of Fabry patients. In this review the authors describe clinical
      features of Fabry disease in 31 Hungarian patients. At the time of this analysis
      the database consisted of 31 cases (15 males, 16 females) of whom 5 have died (4
      males, 1 female). The most common disease-specific manifestation was
      angiokeratoma in males, and eye symptoms in females. 25% of female subjects were
      symptom free. Genotyping was performed in all cases and disease-causing mutations
      were found in all families. Three new mutations were identified. Twelve patients
      (8 males and 4 females) are currently receiving enzyme replacement therapy.

PMID- 17545118
TI  - [Significance of metal ion metabolism and oxidative stress in male patients with
      porphyria cutanea tarda].
AB  - In the last decades, the role of oxidative stress and trace elements was proven
      to play an important role in the pathogenesis of more and more diseases. This is
      why a great importance is attributed lately to the antioxidant therapy, and lots
      of studies are dealing with this issue. In porphyria cutanea tarda (PCT) the
      biosynthesis of hem is damaged, because of the reduced activity of
      uroporphyrinogen-decarboxylase enzyme. The hem precursors are accumulating in
      blood, liver and skin. The hem precursors and porphyrin are eliminated with urine
      and stool. The enzyme defect is autosomal dominant. The skin symptoms are
      intensified by sun exposure. This is because the accumulation of uroporphyrins
      and heptacarboxylporphyrin in the skin causes photosensitivity, and the
      accumulated iron has a lipid-peroxidation effect. Besides the genetical origin,
      the alcohol consumption, the hepatotoxic drugs, estrogen and viral infections can
      also determine the development of the disease. The applied treatment is
      phlebotomy. In the case of PCT that appears in the field of liver damage, the
      accumulation of iron is responsible for the development of oxidative stress. The
      patient's redox homeostasis is changed, and the level of antioxidants is
      decreased. The redox state of liver and the effects of additional antioxidant
      treatment in phlebotomized PCT patients were determined by biochemical and trace
      element analytical methods. According to the clinical data, phlebotomy proved to
      be an effective treatment in PCT patients. Phlebotomy improved the phototoxic
      skin symptoms, but it did not improve the ratios of trace elements to each other
      in the blood of the patients.

PMID- 17545121
TI  - ["Laboratory without walls." Interview with Dr. Jozsef Molnar by B. Kiraly
      Gyorgyi].

PMID- 17545122
TI  - Anchorage of mature conifers: resistive turning moment, root-soil plate geometry
      and root growth orientation.
AB  - Eighty-four mature Norway spruce (Picea abies L. Karst), silver fir (Abies alba
      Mill) and Scots pine (Pinus sylvestris L.) trees were winched over to determine
      the maximum resistive turning moment (M(a)) of the root-soil system, the root
      soil plate geometry, the azimuthal orientation of root growth, and the occurrence
      of root rot. The calculation of M(a), based on digital image tracking of stem
      deflection, accounted not only for the force application and its changing
      geometry, but also for the weight of the overhanging tree, representing up to 42%
      of M(a). Root rot reduced M(a) significantly and was detected in 25% of the
      Norway spruce and 5% of the silver fir trees. Excluding trees with root rot,
      differences in M(a) between species were small and insignificant. About 75% of
      the variance in M(a) could be explained by one of the four variables--tree mass,
      stem mass, stem diameter at breast height squared times tree height, and stem
      diameter at breast height squared. Among the seven allometric variables assessed
      above ground, stem diameter at breast height best described the root-soil plate
      dimensions, but the correlations were weak and the differences between species
      were insignificant. The shape of the root-soil plate was well described by a
      depth-dependent taper model with an elliptical cross section. Roots displayed a
      preferred azimuthal orientation of growth in the axis of prevailing winds, and
      the direction of frequent weak winds matched the orientation of growth better
      than that of rare strong winds. The lack of difference in anchorage parameters
      among species probably reflects the similar belowground growth conditions of the
      mature trees.

PMID- 17545123
TI  - Fresh-wood bending: linking the mechanical and growth properties of a Norway
      spruce stem.
AB  - To provide data and methods for analyzing stem mechanics, we investigated
      bending, density and growth characteristics of 207 specimens of fresh wood from
      different heights and radial positions of the stem of one mature Norway spruce
      (Picea abies L. Karst.) tree. From the shape of each stress-strain curve, which
      was calculated from bending tests that accounted for shear deformation, we
      determined the modulus of elasticity (MOE), the modulus of rupture (MOR), the
      completeness of the material, an idealized stress-strain curve and the work
      involved in bending. In general, all mechanical properties increased with
      distance from the pith, with values in the ranges of 5.7-18 GPa for MOE, 23-90
      MPa for MOR and 370-630 and 430-1100 kg m(-3) for dry and fresh wood densities,
      respectively. The first three properties generally decreased with stem height,
      whereas fresh wood density increased. Multiple regression equations were
      calculated, relating MOR, MOE and dry wood density to growth properties. We
      applied these equations to the growth of the entire stem and considered the
      annual rings as superimposed cylindrical shells, resulting in stem-section values
      of MOE, MOR and dry and fresh densities as a function of stem height and cambial
      age. The standing tree exhibits an inner stem structure that is well designed for
      bending, especially at a mature stage.

PMID- 17545124
TI  - Isolation of genes up-regulated by copper in a copper-tolerant birch (Betula
      pendula) clone.
AB  - Suppression subtractive hybridization (SSH) was used to isolate genes
      differentially expressed following exposure to copper (Cu) in a naturally
      selected Cu-tolerant birch (Betula pendula Roth.) clone originating from a
      disused lead/zinc smelter. Of the 352 cDNA fragments initially isolated, 108 were
      up-regulated by Cu, of which 55 showed over twofold induction by macroarray
      analysis. Searches against protein databases (Blastx) and sequence analysis
      provided the tentative identity of 21 genes. Three fragments lacked homology to
      any sequences in the databases. Most of the identified genes are involved in
      cellular transport, regulation or cell rescue and defense. Several genes have not
      previously been reported to be up-regulated by Cu, e.g., plasma intrinsic protein
      2, glutamine synthetase and multi-drug resistance-associated protein (MRP4). The
      expression of MRP4, a vacuolar sorting receptor-like protein and an unidentified
      gene was studied in more detail by quantitative real-time PCR. These genes showed
      stronger up-regulation by Cu in the roots and shoots of the Cu-tolerant birch
      clone compared with a less tolerant clone. Clear clonal differences in gene
      expression were observed, e.g., for the regulator of chromosome condensation
      family protein, DnaJ protein homolog, vacuolar sorting receptor-like protein and
      MRP4. These findings contribute to our understanding of Cu tolerance in birch, a
      pioneer plant in metal-contaminated soils.

PMID- 17545125
TI  - Tea (Camellia sinensis) clones with shorter periods of winter dormancy exhibit
      lower accumulation of reactive oxygen species.
AB  - Tea (Camellia sinensis (L.) O. Kuntze) is a perennial crop grown throughout the
      world. During winter, tea undergoes a dormancy period when growth of apical buds
      almost ceases, severely reducing the commercial yield of tea. Low temperatures
      prevail during the period of winter dormancy, which alone or in combination with
      high solar irradiance have the potential to induce oxidative stress in plants. We
      studied six tea clones under field conditions to test whether a relationship
      exists between oxidative stress and winter dormancy. Data on the behavior of the
      enzymatic antioxidative system was collected for all clones during different
      phases of winter dormancy. There was a strong positive correlation among clones
      between accumulation of reactive oxygen species (ROS) and the length of the
      dormancy period. Clones having shorter dormancy periods exhibited higher
      induction of antioxidative enzymes. Results suggest that efficient scavenging of
      ROS is a desirable feature in tea because it leads to lower accumulations of ROS
      during winter months and is associated with reduced winter dormancy.

PMID- 17545126
TI  - Molecular identification and characterization of Tcmago and TcY14 in Taiwania
      (Taiwania cryptomerioides).
AB  - Mago nashi (Mago) and Y14 proteins are highly conserved among eukaryotes, and not
      only play important roles in oogenesis, embryogenesis and germ-line determination
      during animal development, but also participate in mRNA localization and splicing
      in cell growth. We identified mago (Tcmago) and Y14 (TcY14) homologues derived
      from expressed sequence tags of Taiwania cryptomerioides Hayata seedlings. Tcmago
      and TcY14 contain coding regions encoding 149 and 216 amino acids, respectively.
      Multiple amino acid sequence alignments as well as secondary and tertiary
      structure all predicted that TcMago and TcY14 possessed similar protein
      structures to the crystal structures of Drosophila melanogaster and human Mago
      and Y14 proteins. We demonstrated by yeast two-hybrid analysis and a GST pull
      down assay that TcMago and TcY14 interacted in vivo and in vitro, confirming
      structural predictions of their interaction. TcMago and TcY14 were predominately
      localized in the nucleus. Whole mount in situ hybridization and
      immunolocalization showed that Tcmago and TcY14 were both detected in root hairs
      at the levels of transcription and protein expression. Overexpression of Tcmago
      in transgenic tobacco plants resulted in longer roots and a more complex root
      system. TcMago and TcY14 may have cellular functions similar to the Mago and Y14
      proteins in animals and may be involved in root development in plants.

PMID- 17545127
TI  - Molecular cloning, expression analyses and primary evolution studies of REV- and
      TB1-like genes in bamboo.
AB  - Most cultured bamboos are perennial woody evergreens that reproduce from
      rhizomes. It is unclear why some rhizome buds develop into aerial bamboo shoots
      instead of new rhizomes. REVOLUTA (REV)-like Class III homeodomain leucine-zipper
      (HD-Zip) proteins and TEOSINTE BRANCHED1 (TB1)-like transcription factors have
      been shown to play regulatory roles in meristem initiation and outgrowth. We
      cloned and analyzed the bamboo (Phyllostachys praecox C.D. Chu & C.S. Chao.) REV-
      (PpHB1) and TB1-like (PpTB1) gene. Gene expression was mainly detected by in situ
      hybridization. PpHB1 expression was detected in the tips of lateral buds, on the
      adaxial portion of the leaf and within the developing procambium, indicating its
      close correlation to rhizome bud formation and procambial development. PpTB1
      expression was mainly detected on the top of buds at later developmental stages,
      suggesting it was more likely involved in bud outgrowth. Meristem genes might
      therefore serve as specific molecular markers of rhizome bud development and
      could be useful in studies designed to elucidate the mechanisms underlying bamboo
      shoot development. In addition, meristem genes such as TB1-like sequences may be
      useful in phylogenetic analyses of bamboo species.

PMID- 17545128
TI  - The aspartate aminotransferase family in conifers: biochemical analysis of a
      prokaryotic-type enzyme from maritime pine.
AB  - Plant aspartate aminotransferase (AAT, EC 2.6.1.1) plays a key role in primary
      nitrogen assimilation, the transfer of reducing equivalents and the interchanges
      of carbon and nitrogen pools between subcellular compartments. We investigated
      the AAT family in conifers using maritime pine as the experimental model. Genes
      for cytosolic, mitochondrial and two plastidic isoenzymes (eukaryotic- and
      prokaryotic-types) were identified and their deduced amino acid sequences
      compared. The primary structure of the eukaryotic-type enzymes is quite well
      conserved, whereas the prokaryotic-type AAT is highly divergent (15% of
      identity). These molecular data were confirmed by the absence of immunological
      cross-reactivity between the two types of native AATs. The mature prokaryotic
      type polypeptide was overexpressed in Escherichia coli, and the native enzyme was
      purified to apparent homogeneity and its molecular properties determined. The
      fully active recombinant holoenzyme showed highest catalytic activity at 50-60
      degrees C and was moderately thermostable, retaining about 50% of its activity
      after incubation at 70 degrees C for 5-10 min. The presence of pyridoxal 5'
      phosphate significantly increased the thermostability of the enzyme. These
      molecular characteristics were exploited to develop a rapid protocol for the
      purification of this prokaryotic-type enzyme from pine cotyledons. The results
      will be useful for studying aspartate and amino acid metabolism in trees.

PMID- 17545129
TI  - Acclimation of leaves to contrasting irradiance in juvenile trees differing in
      shade tolerance.
AB  - Leaves developing in different irradiances undergo structural and functional
      acclimation, although the extent of trait plasticity is species specific. We
      tested the hypothesis that irradiance-induced plasticity of photosynthetic and
      anatomical traits is lower in highly shade-tolerant species than in moderately
      shade-tolerant species. Seedlings of two evergreen conifers, shade-tolerant Abies
      alba Mill. and moderately shade-tolerant Picea abies Karst., and two deciduous
      angiosperm species, highly shade-tolerant Fagus sylvatica L. and moderately shade
      tolerant Acer pseudoplatanus L., were grown in deep shade (LL, 5% of full
      irradiance) or in full solar irradiance (HL) during 2003 and 2004. Steady state
      responses of quantum yield of PSII (Phi(PSII)), apparent electron transport rate
      (ETR), nonphotochemical quenching (NPQ) and photochemical quenching (qP) were
      generally modified by the light environment, with slower declines in Phi(PSII)
      and qP and greater maximal ETR and NPQ values in HL plants in at least one
      season; however, no link between quantitative measures of plasticity of these
      traits and shade tolerance was found. Plasticity of nine anatomical traits
      (including palisade cell length, which was reduced in LL) showed no relationship
      with shade tolerance, but was less in conifers than in deciduous trees,
      suggesting that leaf life span may be a significant correlate of plasticity. When
      LL-acclimated plants were exposed to HL conditions, the degree and duration of
      photoinhibition (measured as a decline in maximum quantum yield) was greatest in
      F. sylvatica, much lower in P. abies and A. alba, and lowest in A.
      pseudoplatanus. Thus, as with the other traits studied, vulnerability to
      photoinhibition showed no relationship with shade tolerance.

PMID- 17545130
TI  - Photosynthesis in response to sink-source activity and in relation to end
      products and activities of metabolic enzymes in peach trees.
AB  - Fruits were removed (-fruit) or retained (+fruit) on limbs of 'Yanfengyihao'
      peach (Prunus persica (L.) Batch) trees. In addition to the -fruit and +fruit
      treatments, leaves on 1-year-old fruit-bearing shoots of 'Bayuecui' peach trees
      were covered with bags for varying periods of time. Net photosynthetic rate
      (P(n)), stomatal conductance and transpiration rate around midday significantly
      decreased in the -fruit treatment and significantly increased in bagged leaves
      after removal of the bags compared with values in the +fruit treatment. Leaf
      temperature (T(l)) was higher in the -fruit treatment than in the +fruit
      treatment, and P(n) decreased in the -fruit treatment, especially when T(l)
      exceeded 38 and 36 degrees C in 'Yanfengyihao' and 'Bayuecui', respectively.
      Fruit removal resulted in a significant accumulation of sorbitol and starch in
      leaves, but it did not decrease activities of enzymes involved in carbon
      metabolism in leaves of 'Yanfengyihao'. In contrast, activities of aldose-6
      phosphate reductase and ADP-glucose pyrophosphorylase sometimes increased in
      leaves in the -fruit treatment. In 'Bayuecui', fruit removal significantly
      decreased maximal fluorescence and photochemical efficiency and increased minimal
      fluorescence around midday compared with values in the +fruit and bag treatments.
      The photosynthetic apparatus of peach may be damaged when T(l) exceeds a critical
      temperature under conditions of decreased sink demand. Decreased stomatal
      aperture and increased T(l) may regulate photosynthesis by affecting electron
      transport.

PMID- 17545131
TI  - Assessing nitrogen fixation in mixed- and single-species plantations of
      Eucalyptus globulus and Acacia mearnsii.
AB  - Mixtures of Eucalyptus globulus Labill. and Acacia mearnsii de Wildeman are twice
      as productive as E. globulus monocultures growing on the same site in East
      Gippsland, Victoria, Australia, possibly because of increased nitrogen (N)
      availability owing to N(2) fixation by A. mearnsii. To investigate whether N(2)
      fixation by A. mearnsii could account for the mixed-species growth responses, we
      assessed N(2) fixation by the accretion method and the (15)N natural abundance
      method. Nitrogen gained by E. globulus and A. mearnsii mixtures and monocultures
      was calculated by the accretion method with plant and soil samples collected 10
      years after plantation establishment. Nitrogen in biomass and soil confirmed that
      A. mearnsii influenced N dynamics. Assuming that the differences in soil, forest
      floor litter and biomass N of plots containing A. mearnsii compared with E.
      globulus monocultures were due to N(2) fixation, the 10-year annual mean rates of
      N(2) fixation were 38 and 86 kg ha(-1) year(-1) in 1:1 mixtures and A. mearnsii
      monocultures, respectively. Nitrogen fixation by A. mearnsii could not be
      quantified on the basis of the natural abundance of (15)N because such factors as
      mycorrhization type and fractionation of N isotopes during N cycling within the
      plant confounded the effect of the N source on the N isotopic signature of
      plants. This study shows that A. mearnsii fixed significant quantities of N(2)
      when mixed with E. globulus. A decline in delta(15)N values of E. globulus and A.
      mearnsii with time, from 2 to 10 years, is further evidence that N(2) was fixed
      and cycled through the stands. The increased aboveground biomass production of E.
      globulus trees in mixtures when compared with monocultures can be attributed to
      increases in N availability.

PMID- 17545132
TI  - Elevated temperature and CO(2) concentration effects on xylem anatomy of Scots
      pine.
AB  - We studied the effects of elevated temperature and carbon dioxide concentration
      ([CO(2)]) alone and together on wood anatomy of 20-year-old Scots pine (Pinus
      sylvestris L.) trees. The study was conducted in 16 closed chambers, providing a
      factorial combination of two temperature regimes and two CO(2) concentrations
      (ambient and elevated), with four trees in each treatment. The climate scenario
      included a doubling of [CO(2)] and a corresponding increase of 2-6 degrees C in
      temperature at the site depending on the season. Anatomical characteristics
      analyzed were annual earlywood, latewood and ring widths, intra-ring wood
      densities (earlywood, latewood and mean wood density), tracheid width, length,
      wall thickness, lumen diameter, wall thickness:lumen diameter ratio and mass per
      unit length (coarseness), and numbers of rays, resin canals and tracheids per
      xylem cross-sectional area. Elevated [CO(2)] increased ring width in four of six
      treatment years; earlywood width increased in the first two years and latewood
      width in the third year. Tracheid walls in both the earlywood and latewood tended
      to become thicker over the 6-year treatment period when temperature or [CO(2)]
      was elevated alone, whereas in the combined treatment they tended to become
      thinner relative to the tracheids of trees grown under ambient conditions.
      Latewood tracheid lumen diameters were larger in all the treatments relative to
      ambient conditions over the 6-year period, whereas lumen diameters in earlywood
      increased only in response to elevated [CO(2)] and were 3-6% smaller in the
      treatments with elevated temperature than in ambient conditions. Tracheid width,
      length and coarseness were greater in trees grown in elevated than in ambient
      temperature. The number of resin canals per mm(2) decreased in the elevated
      [CO(2)] treatment and increased in the elevated temperature treatments relative
      to ambient conditions. The treatments decreased the number of rays and tracheids
      per mm(2) of cross-sectional area, the greatest decrease occurring in the
      elevated [CO(2)] treatment. It seemed that xylem anatomy was affected more by
      elevated temperature than by elevated [CO(2)] and that the effects of temperature
      were confined to the earlywood.

PMID- 17545133
TI  - Variation in drought resistance, drought acclimation and water conservation in
      four willow cultivars used for biomass production.
AB  - Growth and water-use parameters of four willow (Salix spp.) clones grown in a
      moderate drought regime or with ample water supply were determined to
      characterize their water-use efficiency, drought resistance and capacity for
      drought acclimation. At the end of the 10-week, outdoor pot experiment, clonal
      differences were observed in: (1) water-use efficiency of aboveground biomass
      production (WUE); (2) resistance to xylem cavitation; and (3) stomatal
      conductance to leaf-specific, whole-plant hydraulic conductance ratio
      (g(st)/K(P); an indicator of water balance). Across clones and regimes, WUE was
      positively correlated with the assimilation rate to stomatal conductance ratio
      (A/g(st)), a measure of instantaneous water-use efficiency. Both of these water
      use efficiency indicators were generally higher in drought-treated trees compared
      with well-watered trees. However, the between-treatment differences in (shoot
      based) WUE were smaller than expected, considering the differences in A/g(st) for
      two of the clones, possibly because plants reallocated dry mass from shoots to
      roots when subject to drought. Higher root hydraulic conductance to shoot
      hydraulic conductance ratios (K(R)/K(S)) during drought supports this hypothesis.
      The same clones were also the most sensitive to xylem cavitation and,
      accordingly, showed the strongest reduction in g(st)/K(P) in response to drought.
      Drought acclimation was manifested in decreased g(st), g(st)/K(P), osmotic
      potential and leaf area to vessel internal cross-sectional area ratio, and
      increased K(R), K(P) and WUE. Increased resistance to stem xylem cavitation in
      response to drought was observed in only one clone. It is concluded that WUE and
      drought resistance traits are inter-linked and that both may be enhanced by
      selection and breeding.

PMID- 17545134
TI  - Intra-annual height increment of Pinus sylvestris at high latitudes in Finland.
AB  - Intra-annual height growth of Scots pine (Pinus sylvestris L.) in four stands was
      followed for up to four growing seasons (2000-2003) in the northern boreal zone
      in Lapland. Elongation of the leader shoot correlated with temperature sum
      expressed as degree-days. Total length of the leader shoot correlated with growth
      rate but not with duration of the height-growth period. The longer the annual
      shoot at the end of the season, the greater the height increment per degree- and
      growing day. Height-growth cessation was defined as the date when 95% of the
      total shoot length was achieved. In all stands and all years, height growth
      ceased when, on average, 41% of the relative temperature sum of the site was
      achieved (range of variation 38-43%). The relative temperature sum was calculated
      by dividing the actual temperature sum by the long-term mean for the site. Our
      results suggest that annual height growth is finished when a location-specific
      temperature sum threshold is attained.

PMID- 17545135
TI  - A comparison of daily water use estimates derived from constant-heat sap-flow
      probe values and gravimetric measurements in pot-grown saplings.
AB  - Use of Granier-style heat dissipation sensors to measure sap flow is common in
      plant physiology, ecology and hydrology. There has been concern that any change
      to the original Granier design invalidates the empirical relationship between sap
      flux density and the temperature difference between the probes. Here, we compared
      daily water use estimates from gravimetric measurements with values from variable
      length heat dissipation sensors, which are a relatively new design. Values
      recorded during a one-week period were compared for three large pot-grown
      saplings of each of the tropical trees Pseudobombax septenatum (Jacq.) Dugand and
      Calophyllum longifolium Willd. For five of the six individuals, P values from
      paired t-tests comparing the two methods ranged from 0.12 to 0.43 and differences
      in estimates of total daily water use over the week of the experiment averaged <
      3%. In one P. septenatum sapling, the sap flow sensors underestimated water use
      relative to the gravimetric measurements. This discrepancy could have been
      associated with naturally occurring gradients in temperature that reduced the
      difference in temperature between the probes, which would have caused the sensor
      method to underestimate water use. Our results indicate that substitution of
      variable length heat dissipation probes for probes of the original Granier design
      did not invalidate the empirical relationship determined by Granier between sap
      flux density and the temperature difference between probes.

PMID- 17545136
TI  - Genetic counseling and presenilin-1 Alzheimer's disease: "Research Family"
      members share some thoughts.
AB  - Genetic counseling is a 2-way street between counselor and the counseled. In this
      article, both share experiences gained through more than 25 years of searching
      for the gene, finding the presenilin-1 Alzheimer's disease gene, and waiting for
      a cure. "Research Families" made research models a reality. Few family members
      requested presymptomatic testing.

PMID- 17545137
TI  - Perceptions of the process of care among caregivers and care recipients in
      dementia care networks.
AB  - The Dementia Care Networks Study investigated 4 community-based, not-for-profit
      dementia care networks in Ontario, Canada. Investigators examined whether
      sociodemographic and health characteristics, type of support network, and amount
      of service use among care recipients and caregivers (n = 267 dyads) were
      associated with experiences with care processes. The process-of-care constructs
      were: family physicians' awareness of services; experiences with health care
      workers, and assessment and placement activities. The findings highlighted that
      family physicians' understanding of dementia and their ability to work with the
      dyad to become aware of and accept services, was an important component in the
      dyad's satisfaction. If caregivers received home support and the care recipients
      received emotional support from their social support network, they were more
      likely to be satisfied with their experiences with health care workers. In
      summary, increased awareness and provision of services were associated with more
      positive perceptions of network effectiveness.

PMID- 17545138
TI  - Use of the certified nursing assistant pain assessment tool (CPAT) in nursing
      home residents with dementia.
AB  - The purpose of this study was to develop a pain assessment tool utilized by
      certified nursing assistant (CNA) direct-care providers for nursing home
      residents with dementia and to examine the impact of such a tool on their
      function, behavior, or medication use. In the first phase, 41 items from an
      observational pain assessment tool were correlated with an objective pain "gold
      standard"; 12 statistically significant items were retained and used in the CNA
      pain assessment tool. Symmetry analysis was then conducted to determine if this
      resulted in any significant change in resident function, behavior, or medication
      use. This failed to detect significant change in these characteristics. A pain
      assessment tool utilized by CNA direct-care providers can be developed for use in
      nursing home residents with dementia. Further study is required to determine
      whether the use of such a tool will improve their function or quality of life.

PMID- 17545139
TI  - Comparative outcomes of two distance-based interventions for male caregivers of
      family members with dementia.
AB  - Data are presented on a preliminary study investigating the efficacy of 2
      distance-based psychosocial interventions (N = 32) for male family dementia
      caregivers. Male caregivers were randomly assigned to either a basic education
      intervention (ie, educational booklet and biweekly check-in telephone calls) or a
      video intervention (ie, set of 10 videos, an accompanying workbook, and weekly
      telephone coaching sessions using behavioral strategies to manage challenging
      caregiving situations). Results did not support the greater efficacy of the video
      condition in reducing psychosocial distress (eg, negative affect, upset and
      annoyance following behavior problems) or increasing positive affect or
      caregiving self-efficacy. There was, however, a statistically significant effect
      for postintervention improvement in both the video/coaching and the educational
      booklet/check-in conditions. Potential reasons for the lack of differential
      treatment effects are discussed, along with implications for recruitment of male
      dementia caregivers.

PMID- 17545140
TI  - Feasibility study of the integrated circuit tag monitoring system for dementia
      residents in Japan.
AB  - Videotaping, direct observation, and biomechanical devices have been used to
      measure the wandering behavior of institutionalized people with dementia and to
      identify patterns of movement. Owing to technical limitations, the variability in
      movement patterns or the distance traveled could not be examined. The present
      study examined the feasibility of an integrated circuit tag monitoring system to
      monitor the movement patterns of Japanese dementia residents. This system
      generated the following data: the frequency of detection by each receiver, the
      duration of stay in each location, the cumulative distance walked per day, and
      the graphic display of the movement pattern. This new system offers objective
      measurements of ambulation in time and space, which can be used to characterize
      demented patients and to evaluate the effects of treatment and care.

PMID- 17545141
TI  - Presenilin-1 C410Y Alzheimer disease plaques contain synaptic proteins.
AB  - Presenilin-1 (PS-1) mutations are associated with familial Alzheimer's disease
      (AD). Although beta-amyloid (Abeta) plaques in brain tissue are characteristic of
      AD patients, space occupying "cotton-wool" plaques (CWPs) lacking dense Abeta
      cores have also been described in patients with mutations in exon 9 of the PS-1
      gene. The composition of CWPs has not been fully described. To better elucidate
      the composition of these space-occupying plaques, we used immunohistochemistry
      with antibodies to the synaptic proteins synapsin-1 and synaptophysin, as well as
      antibodies to tau, Abeta(-42), Abeta(-40), ubiquitin, neurofilament, and glial
      fibrillary acidic protein. Confocal laser scanning microscopy (CLSM) was utilized
      to further characterize these plaques. CWPs showed increased synapsin-1 and
      synaptophysin immunoreactivity relative to the background gray matter. Synaptic
      protein-containing CWPs occurred in all affected MTL regions, including the
      granule cell layer of the dentate gyrus, where synaptic terminals are usually
      sparse. These data suggest that in C410Y PS-1 AD patients, CWPs may constitute a
      major component of synaptic terminal-specific proteins, and that the C410Y PS-1
      mutation may influence either synaptic structure or synaptic protein expression.

PMID- 17545143
TI  - Reversibility of antimicrobial resistance in respiratory isolates in HIV-positive
      Cambodian children after 36 months of HAART.

PMID- 17545144
TI  - Hospital-acquired pneumonia guidelines in Europe: a review of their status and
      future development.
AB  - Hospital-acquired pneumonia (HAP) is the most common healthcare-acquired
      infection contributing to death. Effective management requires accurate
      diagnosis, administration of a suitable antibiotic regimen early in infection and
      implementation of prevention strategies. In recent years, there has been a rapid
      increase in the number of country-specific HAP guidelines in Europe, which vary
      in their formulation, coverage of different disease aspects and overall
      recommendations. Development of comprehensive pan-European HAP guidelines would
      rationalize the conflicting proposals, provide a useful resource and limit
      guideline proliferation. However, careful consideration needs to be given to the
      principles of guideline development to ensure that the output is rigorous,
      broadly applicable and facilitates update as new data becomes available. The use
      of an evidence-based approach to HAP guideline development is optimal, but is
      compromised by limitations in the supporting data. The implementation of a
      formalized evidence grading system is key to introducing consistency into the
      guideline development process. Pan-European guidelines should provide
      recommendations on core aspects of HAP common to all treatment settings and
      locations, and reflect the differing perspectives of the countries involved.
      Given the different antibiotic susceptibility profiles across Europe, such
      guidelines should provide general treatment recommendations suitable for local
      adaptation. The development of such guidelines represents an ideal time to
      identify priorities for European research, by addressing controversies and
      identifying previously unconsidered aspects of HAP. Establishing a pan-European
      consensus on core processes of care should be viewed as an impetus for change to
      improve clinical practices and should include a suitable implementation strategy.

PMID- 17545145
TI  - Interactions of human rad54 protein with branched DNA molecules.
AB  - The Rad54 protein plays an important role during homologous recombination in
      eukaryotes. The protein belongs to the Swi2/Snf2 family of ATP-dependent DNA
      translocases. We previously showed that yeast and human Rad54 (hRad54)
      specifically bind to Holliday junctions and promote branch migration. Here we
      examined the minimal DNA structural requirements for optimal hRad54 ATPase and
      branch migration activity. Although a 12-bp double-stranded DNA region of
      branched DNA is sufficient to induce ATPase activity, the minimal substrate that
      gave rise to optimal stimulation of the ATP hydrolysis rate consisted of two
      short double-stranded DNA arms, 15 bp each, combined with a 45-nucleotide single
      stranded DNA branch. We showed that hRad54 binds preferentially to the open and
      not to the stacked conformation of branched DNA. Stoichiometric titration of
      hRad54 revealed formation of two types of hRad54 complexes with branched DNA
      substrates. The first of them, a dimer, is responsible for the ATPase activity of
      the protein. However, branch migration activity requires a significantly higher
      stoichiometry of hRad54, approximately 10 +/- 2 protein monomers/DNA molecule.
      This pleomorphism of hRad54 in formation of oligomeric complexes with DNA may
      correspond to multiple functions of the protein in homologous recombination.

PMID- 17545146
TI  - Control and regulation of KplE1 prophage site-specific recombination: a new
      recombination module analyzed.
AB  - KplE1 is one of the 10 prophage regions of Escherichia coli K12, located at 2464
      kb on the chromosome. KplE1 is defective for lysis, but it is fully competent for
      excisive recombination. In this study, we have mapped the binding sites of the
      recombination proteins, namely IntS, TorI, and IHF on attL and attR, and the
      organization of these sites suggests that the intasome is architecturally
      different from the lambda canonical form. We also measured the relative
      contribution of these proteins to both excisive and integrative recombination by
      using a quantitative in vitro assay. These experiments show a requirement of the
      TorI excisionase for excisive recombination and of the IntS integrase for both
      integration and excision. Moreover, we observed a strong influence of the
      supercoiled state of the substrates. The KplE1 recombination module, composed of
      the integrase and excisionase genes together with the attL and attR DNA regions,
      is highly similar to that of several phages infecting various E. coli strains as
      well as Shigella flexneri and Shigella sonnei. The in vitro recombination data
      reveal that HK620 and KplE1 att sequences are exchangeable. This study thus
      defines a new site-specific recombination module, and implications for the
      mechanism and regulation of recombination are discussed.

PMID- 17545147
TI  - Insulin-like growth factor type-I receptor internalization and recycling mediate
      the sustained phosphorylation of Akt.
AB  - Previously we demonstrated that insulin-like growth factor-I mediates the
      sustained phosphorylation of Akt, which is essential for long term survival and
      protection of glial progenitors from glutamate toxicity. These prosurvival
      effects correlated with prolonged activation and stability of the insulin-like
      growth factor type-I receptor. In the present study, we investigated the
      mechanisms whereby insulin-like growth factor-I signaling, through the insulin
      like growth factor type-I receptor, mediates the sustained phosphorylation of
      Akt. We showed that insulin-like growth factor-I stimulation induced loss of
      receptors from the cell surface but that surface receptors recovered over time.
      Blocking receptor internalization inhibited Akt phosphorylation, whereas
      inhibition of receptor trafficking blocked receptor recovery at the cell surface
      and the sustained phosphorylation of Akt. Moreover the insulin-like growth factor
      type-I receptor localized with the transferrin receptor and Rab11-positive
      endosomes in a ligand-dependent manner, further supporting the conclusion that
      this receptor follows a recycling pathway. Our results provide evidence that
      ligand stimulation leads to internalization of the insulin-like growth factor
      type-I receptor, which mediates Akt phosphorylation, and that receptor recycling
      sustains Akt phosphorylation in glial progenitors. Mathematical modeling of
      receptor trafficking further supports these results and predicts an additional
      kinetic state of the receptor consistent with sustained Akt phosphorylation.

PMID- 17545148
TI  - GAPex-5 mediates ubiquitination, trafficking, and degradation of epidermal growth
      factor receptor.
AB  - Upon ligand stimulation, epidermal growth factor receptor (EGFR) is rapidly
      ubiquitinated, internalized, and sorted to lysosomes for degradation. Rab5 has
      been shown to play an important role in the early stages of EGFR trafficking.
      GAPex-5 is a newly described Rab5 exchange factor. Herein, we investigate the
      role of GAPex-5 on EGFR trafficking and degradation. Down-regulation of GAPex-5
      by RNA interference decreases epidermal growth factor-stimulated EGFR
      degradation. Moreover, ubiquitination of EGFR is impaired by depletion of GAPex
      5. This inhibitory effect is due to a decrease in the interaction between the
      adapter protein c-Cbl and EGFR, but not the phosphorylation state of EGFR.
      Consistently, when examined by immunofluorescence microscopy in cells depleted of
      GAPex-5, ligand-bound EGFR appeared trapped in early endosomes and the
      trafficking of internalized receptor from early to late endosomes was impaired.
      In agreement with the depletion studies, EGFR degradation is enhanced by
      overexpressing GAPex-5 wild type, but not GAPex-5DeltaGAP, a mutant lacking the
      Ras GTPase-activating protein (GAP) domain. This is consistent with the finding
      that c-Cbl binds specifically to the Ras GAP domain. Finally, overexpression of
      dominant negative Rab5a or depletion of all three isoforms of Rab5 does not
      inhibit ubiquitination of EGFR, which suggests that GAPex-5-mediated EGFR
      ubiquitination is independent of Rab5 activation. Collectively, the results
      suggest a novel mechanism by which EGF-stimulated receptor ubiquitination and
      trafficking are mediated via GAPex-5.

PMID- 17545149
TI  - Amino acid transport in schistosomes: Characterization of the permeaseheavy chain
      SPRM1hc.
AB  - Schistosomes are human parasitic flatworms that constitute an important public
      health problem globally. Adult parasites live in the bloodstream where they
      import nutrients such as amino acids across their body surface (the tegument).
      One amino acid transporter, Schistosome Permease 1 light chain, SPRM1lc, a member
      of the glycoprotein-associated family of transporters (gpaAT), has been
      characterized in schistosomes. Only a single member of the SLC3 family of
      glycoproteins that associate with gpaATs is found following extensive searching
      of the genomes of Schistosoma mansoni and S. japonicum. In this report, we
      characterize this schistosome permease heavy chain (SPRM1hc) gene and protein.
      The 72-kDa gene product is predicted to possess a single transmembrane domain, a
      (betaalpha)(8) (TIM barrel) conformation and a catalytic triad. Xenopus oocytes
      functionally expressing SPRM1hc with SPRM1lc import phenylalanine, arginine,
      lysine, alanine, glutamine, histidine, tryptophan, and leucine. Biochemical
      characterization demonstrates that in Xenopus extracts and in schistosome
      extracts SPRM1hc is associated into a high molecular weight complex with SPRM1lc
      that is disrupted by reducing agents. Quantitative real-time PCR and Western
      analysis demonstrate that SPRM1hc is expressed in each schistosome life stage
      examined (eggs, cercariae, schistosomula, adult males and females). SPRM1hc is
      widely distributed throughout adult male and female worms as determined by
      immunolocalization. Consistent with the hypothesis that SPRM1hc functions to
      facilitate nutrient uptake from host blood, immunogold electron microscopy
      confirms that the protein is distributed on the host-interactive tegumental
      membranes. We propose that surface-exposed, host-interactive, nutrient
      transporting proteins like the SPRM1 heterodimer are promising vaccine
      candidates.

PMID- 17545150
TI  - Biosynthesis of (R)-beta-tyrosine and its incorporation into the highly cytotoxic
      chondramides produced by Chondromyces crocatus.
AB  - The chondramides are mixed non-ribosomal peptide/polyketide secondary metabolites
      produced by the myxobacterium Chondromyces crocatus Cm c5, which exhibit strong
      cytotoxic activity. On the basis of their striking structural similarity to the
      marine depsipeptides jaspamides, the chondramides have been assumed to
      incorporate a (R)-beta-tyrosine moiety, an expectation we confirm here. Thus, the
      recent sequencing of the chondramide biosynthetic gene cluster provided the
      opportunity to probe the shared origin of this unusual beta-amino acid. We
      demonstrate here that (R)-beta-tyrosine is produced directly from l-tyrosine by
      the aminomutase CmdF. Along with the tyrosine aminomutase SgcC4 from the C-1027
      enediyne pathway, this enzyme belongs to a novel family of tyrosine aminomutases
      related to the ammonium lyase family of enzymes but exhibits opposite facial
      selectivity for the hydroxycinnamate intermediate. We also show that the
      adenylation (A) domain in the chondramide pathway, which activates the beta
      tyrosine building block, exhibits the required preference for (R)-beta-tyrosine,
      further arguing against alternative origins for the moiety in the chondramides.
      Comparison to the (S)-beta-tyrosine specific A domain SgcC1 should enhance our
      understanding of the structural and stereochemical determinants guiding amino
      acid selection by non-ribosomal peptide synthetase multienzymes.

PMID- 17545151
TI  - Degradation of hsp70 and other mRNAs in Drosophila via the 5' 3' pathway and its
      regulation by heat shock.
AB  - Two general pathways of mRNA decay have been characterized in yeast. Both start
      with deadenylation. The major pathway then proceeds via cap hydrolysis and 5'
      exonucleolytic degradation whereas the minor pathway consists of 3'
      exonucleolytic decay followed by hydrolysis of the remaining cap structure. In
      higher eukaryotes, these pathways of mRNA decay are believed to be conserved but
      have not been well characterized. We have investigated the decay of the hsp70
      mRNA in Drosophila Schneider cells. As shown by the use of reporter constructs,
      rapid deadenylation of this mRNA is directed by its 3'-untranslated region. The
      main deadenylase is the CCR4.NOT complex; the PAN nuclease makes a lesser
      contribution. Heat shock prevents deadenylation not only of the hsp70 but also of
      bulk mRNA. A completely deadenylated capped hsp70 mRNA decay intermediate
      accumulates transiently and is degraded via cap hydrolysis and 5'-decay. Thus,
      decapping is a slow step in the degradation pathway. Cap hydrolysis is also
      inhibited during heat shock. Degradation of reporter RNAs from the 3'-end became
      detectable only upon inhibition of 5'-decay and thus represents a minor decay
      pathway. Because two reporter RNAs and at least two endogenous mRNAs were
      degraded primarily from the 5'-end with cap hydrolysis as a slow step, this
      pathway appears to be of general importance for mRNA decay in Drosophila.

PMID- 17545152
TI  - Activation and inhibition of photoreceptor guanylyl cyclase by guanylyl cyclase
      activating protein 1 (GCAP-1): the functional role of Mg2+/Ca2+ exchange in EF
      hand domains.
AB  - Guanylyl cyclase activating protein 1 (GCAP-1), a Ca(2+)/Mg(2+) sensor protein
      that accelerates retinal guanylyl cyclase (RetGC) in the light and decelerates it
      in the dark, is inactive in cation-free form. Binding of Mg(2+) in EF-hands 2 and
      3 was essential for RetGC activation in the conditions mimicking light
      adaptation. Mg(2+) binding in EF-hand 2 affected the conformation of a
      neighboring non-metal binding domain, EF-hand-1, and increased GCAP-1 affinity
      for RetGC nearly 40-fold compared with the metal-free EF-hand 2. Mg(2+) binding
      in EF-hand 3 increased GCAP-1 affinity for RetGC 5-fold and its maximal RetGC
      stimulation 2-fold. Mg(2+) binding in EF-hand 4 affected neither GCAP-1 affinity
      for RetGC, nor RetGC activation. Inactivation of Ca(2+) binding in EF-hand 4 was
      sufficient to render GCAP-1 a constitutive activator of RetGC, whereas the EF
      hand 3 role in Ca(2+)-dependent deceleration of RetGC was likely to be through
      the neighboring EF-hand 4. Inactivation of Ca(2+) binding in EF-hand 2 affected
      cooperativity of RetGC inhibition by Ca(2+), but did not prevent the inhibition.
      We conclude that 1) Mg(2+) binding in EF-hands 2 and 3, but not EF-hand 4, is
      essential for the ability of GCAP-1 to activate RetGC in the light; 2) Mg(2+) or
      Ca(2+) binding in EF-hand 3 and especially in EF-hand 2 is required for high
      affinity interaction with the cyclase and affects the conformation of the
      neighboring EF-hand 1, a domain required for targeting RetGC; and 3) RetGC
      inhibition is likely to be primarily caused by Ca(2+) binding in EF-hand 4.

PMID- 17545153
TI  - Contribution of the conserved amino acids of the melanocortin-4 receptor in
      [corrected] [Nle4,D-Phe7]-alpha-melanocyte-stimulating [corrected] hormone
      binding and signaling.
AB  - Melanocortin 4 receptor (MC4R) plays an important role in the regulation of food
      intake and body weight. To determine the molecular basis of human MC4R (hMC4R)
      responsible for alpha-melanocortin-stimulating hormone (alpha-MSH) binding, in
      this study, we utilized both receptor domain exchange and site-directed
      mutagenesis studies to investigate the molecular determinants of hMC4R
      responsible for alpha-MSH binding and signaling. alpha-MSH is a potent agonist at
      hMC4R but not at hMC2R. Cassette substitutions of the second, third, fourth,
      fifth, and sixth transmembrane regions (TM) of the hMC4R with the homologous
      regions of hMC2R were performed and alpha-MSH binding and signaling were
      examined. Our results indicate that each chimeric receptor was expressed at the
      cell surface and the expression levels remain similar to that of the wild-type
      receptor. The cassette substitutions of the second, fourth, fifth, and sixth TMs
      of the hMC4R with homologous regions of the hMC2R did not significantly alter
      alpha-MSH binding affinity and potency except substitution of the TM3 of the
      hMC4R, suggesting that the conserved residues in TMs of the hMC4R are crucial for
      alpha-MSH binding and signaling. Further mutagenesis studies indicate that
      conserved residues Glu(100) in TM2, Asp(122), Asp(126) in TM3 and Trp(258),
      Phe(261), His(264) in TM6 are involved in alpha-MSH binding and signaling. In
      conclusion, our results suggest that the conserved residues in the TM2, TM3, and
      TM6 of the hMC4R are responsible for alpha-MSH binding and signaling.

PMID- 17545154
TI  - ATP-driven MalK dimer closure and reopening and conformational changes of the
      "EAA" motifs are crucial for function of the maltose ATP-binding cassette
      transporter (MalFGK2).
AB  - We have investigated conformational changes of the purified maltose ATP-binding
      cassette transporter (MalFGK(2)) upon binding of ATP. The transport complex is
      composed of a heterodimer of the hydrophobic subunits MalF and MalG constituting
      the translocation pore and of a homodimer of MalK, representing the ATP
      hydrolyzing subunit. Substrate is delivered to the transporter in complex with
      periplasmic maltose-binding protein (MalE). Cross-linking experiments with a
      variant containing an A85C mutation within the Q-loop of each MalK monomer
      indicated an ATP-induced shortening of the distance between both monomers. Cross
      linking caused a substantial inhibition of MalE-maltose-stimulated ATPase
      activity. We further demonstrated that a mutation affecting the "catalytic
      carboxylate" (E159Q) locks the MalK dimer in the closed state, whereas a
      transporter containing the "ABC signature" mutation Q140K permanently resides in
      the resting state. Cross-linking experiments with variants containing the A85C
      mutation combined with cysteine substitutions in the conserved EAA motifs of MalF
      and MalG, respectively, revealed close proximity of these residues in the resting
      state. The formation of a MalK-MalG heterodimer remained unchanged upon the
      addition of ATP, indicating that MalG-EAA moves along with MalK during dimer
      closure. In contrast, the yield of MalK-MalF dimers was substantially reduced.
      This might be taken as further evidence for asymmetric functions of both EAA
      motifs. Cross-linking also caused inhibition of ATPase activity, suggesting that
      transporter function requires conformational changes of both EAA motifs.
      Together, our data support ATP-driven MalK dimer closure and reopening as crucial
      steps in the translocation cycle of the intact maltose transporter and are
      discussed with respect to a current model.

PMID- 17545155
TI  - Extracellular phosphorylation of collagen XVII by ecto-casein kinase 2 inhibits
      ectodomain shedding.
AB  - Ecto-phosphorylation is emerging as an important mechanism to regulate cellular
      ligand interactions and signal transduction. Here we show that extracellular
      phosphorylation of the cell surface receptor collagen XVII regulates shedding of
      its ectodomain. Collagen XVII, a member of the novel family of collagenous
      transmembrane proteins and component of the hemidesmosomes, mediates adhesion of
      the epidermis to the dermis in the skin. The ectodomain is constitutively shed
      from the cell surface by metalloproteinases of the ADAM (a disintegrin and
      metalloproteinase) family, mainly by tumor necrosis factor-alpha converting
      enzyme (TACE). We used biochemical, mutagenesis, and structural modeling
      approaches to delineate mechanisms controlling ectodomain cleavage. A standard
      assay for extracellular phosphorylation, incubation of intact keratinocytes with
      cell-impermeable [gamma-(32)P]ATP, led to collagen XVII labeling. This was
      significantly diminished by both broad-spectrum extracellular kinase inhibitor
      K252b and a specific casein kinase 2 (CK2) inhibitor. Collagen XVII peptides
      containing a putative CK2 recognition site were phosphorylated by CK2 in vitro,
      disclosing Ser(542) and Ser(544) in the ectodomain as phosphate group acceptors.
      Phosphorylation of Ser(544) in vivo and in vitro was confirmed by immunoblotting
      of epidermis and HaCaT keratinocyte extracts with phosphoepitope-specific
      antibodies. Functionally, inhibition of CK2 kinase activity or mutation of the
      phosphorylation acceptor Ser(544) to Ala significantly increased ectodomain
      shedding, whereas overexpression of CK2alpha inhibited cleavage of collagen XVII.
      Structural modeling suggested that the phosphorylation of serine residues
      prevents binding of TACE to its substrate. Thus, extracellular phosphorylation of
      collagen XVII by ecto-CK2 inhibits its shedding by TACE and represents novel
      mechanism to regulate adhesion and motility of epithelial cells.

PMID- 17545156
TI  - Receptor-mediated regulation of tomosyn-syntaxin 1A interactions in bovine
      adrenal chromaffin cells.
AB  - Tomosyn, a soluble R-SNARE protein identified as a binding partner of the Q-SNARE
      syntaxin 1A, is thought to be critical in setting the level of fusion-competent
      SNARE complexes for neurosecretion. To date, there has been no direct evaluation
      of the dynamics in which tomosyn transits through tomosyn-SNARE complexes or of
      the extent to which tomosyn-SNARE complexes are regulated by secretory demand.
      Here, we employed biochemical and optical approaches to characterize the dynamic
      properties of tomosyn-syntaxin 1A complexes in live adrenal chromaffin cells. We
      demonstrate that secretagogue stimulation results in the rapid translocation of
      tomosyn from the cytosol to plasma membrane regions and that this translocation
      is associated with an increase in the tomosyn-syntaxin 1A interaction, including
      increased cycling of tomosyn into tomosyn-SNARE complexes. The secretagogue
      induced interaction was strongly reduced by pharmacological inhibition of the Rho
      associated coiled-coil forming kinase, a result consistent with findings
      demonstrating secretagogue-induced activation of RhoA. Stimulation of chromaffin
      cells with lysophosphatidic acid, a nonsecretory stimulus that strongly activates
      RhoA, resulted in effects on tomosyn similar to that of application of the
      secretagogue. In PC-12 cells overexpressing tomosyn, secretagogue stimulation in
      the presence of lysophosphatidic acid resulted in reduced evoked secretory
      responses, an effect that was eliminated upon inhibition of Rho-associated coiled
      coil forming kinase. Moreover, this effect required an intact interaction between
      tomosyn and syntaxin 1A. Thus, modulation of the tomosyn-syntaxin 1A interaction
      in response to secretagogue activation is an important mechanism allowing for
      dynamic regulation of the secretory response.

PMID- 17545157
TI  - Expression of human protein phosphatase-1 in Saccharomyces cerevisiae highlights
      the role of phosphatase isoforms in regulating eukaryotic functions.
AB  - Human (PP1) isoforms, PP1alpha, PP1beta, PP1gamma1, and PP1gamma2, differ in
      primary sequences at N and C termini that potentially bind cellular regulators
      and define their physiological functions. The GLC7 gene encodes the PP1 catalytic
      subunit with >80% sequence identity to human PP1 and is essential for viability
      of Saccharomyces cerevisiae. In yeast, Glc7p regulates glycogen and protein
      synthesis, actin cytoskeleton, gene expression, and cell division. We substituted
      human PP1 for Glc7p in yeast to investigate the ability of individual isoforms to
      catalyze Glc7p functions. S. cerevisiae expressing human PP1 isoforms were
      viable. PP1alpha-expressing yeast grew more rapidly than strains expressing other
      isoforms. On the other hand, PP1alpha-expressing yeast accumulated less glycogen
      than PP1beta-or PP1gamma1-expressing yeast. Yeast expressing human PP1 were
      indistinguishable from WT yeast in glucose derepression. However, unlike WT
      yeast, strains expressing human PP1 failed to sporulate. Analysis of chimeric
      PP1alpha/beta subunits highlighted a critical role for their unique N termini in
      defining PP1alpha and PP1beta functions in yeast. Biochemical studies established
      that the differing association of PP1 isoforms with the yeast glycogen-targeting
      subunit, Gac1p, accounted for their differences in glycogen synthesis. In
      contrast to human PP1 expressed in Escherichia coli, enzymes expressed in yeast
      displayed in vitro biochemical properties closely resembling PP1 from mammalian
      tissues. Thus, PP1 expression in yeast should facilitate future structure
      function studies of this protein serine/threonine phosphatase.

PMID- 17545158
TI  - Regulation of the sodium/sulfate co-transporter by farnesoid X receptor alpha.
AB  - Fxralpha is known to regulate a variety of metabolic processes, including bile
      acid, cholesterol, and carbohydrate metabolism. In this study, we show direct
      evidence that Fxralpha is a key player in maintaining sulfate homeostasis. We
      identified and characterized the sodium/sulfate co-transporter (NaS-1; Slc13a1)
      as an Fxralpha target gene expressed in the kidney and intestine. Electromobility
      shift assays, chromatin immunoprecipitation, and promoter reporter studies
      identified a single functional Fxralpha response element in the second intron of
      the mouse Slc13a1 gene. Treatment of wild-type mice with GW4064, a synthetic
      Fxralpha agonist, induced Slc13a1 mRNA in the intestine and kidney. Slc13a1 mRNA
      was also induced in the kidney and intestine of wild-type, but not Fxralpha-/-
      mice, after treatment with the hepatotoxin alpha-naphthylisothiocyanate, which is
      known to result in elevated blood bile acid levels. Finally, we observed a
      decrease in Slc13a1 mRNA in the kidney and intestine of Fxralpha-/- mice and a
      corresponding increase in urinary excretion of free sulfates as compared with
      wild-type mice. These results demonstrate that mouse Slc13a1 is a novel Fxralpha
      target gene expressed in the kidney and intestine and that in the absence of
      Fxralpha, mice waste sulfate into the urine. Thus, Fxralpha is necessary for
      normal sulfate homeostasis in vivo.

PMID- 17545159
TI  - Mitochondrial fission and fusion mediators, hFis1 and OPA1, modulate cellular
      senescence.
AB  - The number and morphology of mitochondria within a cell are precisely regulated
      by the mitochondrial fission and fusion machinery. The human protein, hFis1,
      participates in mitochondrial fission by recruiting the Drp1 into the
      mitochondria. Using short hairpin RNA, we reduced the expression levels of hFis1
      in mammalian cells. Cells lacking hFis1 showed sustained elongation of
      mitochondria and underwent significant cellular morphological changes, including
      enlargement, flattening, and increased cellular granularity. In these cells,
      staining for acidic senescence-associated beta-galactosidase activity was
      elevated, and the rate of cell proliferation was greatly reduced, indicating that
      cells lacking hFis1 undergo senescence-associated phenotypic changes.
      Reintroduction of the hFis1 gene into hFis1-depleted cells restored mitochondrial
      fragmentation and suppressed senescence-associated beta-galactosidase activity.
      Moreover, depletion of both hFis1 and OPA1, a critical component of mitochondrial
      fusion, resulted in extensive mitochondrial fragmentation and markedly rescued
      cells from senescence-associated phenotypic changes. Intriguingly, sustained
      elongation of mitochondria was associated with decreased mitochondrial membrane
      potential, increased reactive oxygen species production, and DNA damage. The data
      indicate that sustained mitochondrial elongation induces senescence-associated
      phenotypic changes that can be neutralized by mitochondrial fragmentation. Thus,
      one of the key functions of mitochondrial fission might be prevention of the
      sustained extensive mitochondrial elongation that triggers cellular senescence.

PMID- 17545160
TI  - Anti-A beta 1-11 antibody binds to different beta-amyloid species, inhibits
      fibril formation, and disaggregates preformed fibrils but not the most toxic
      oligomers.
AB  - Different strategies proposed as therapy for Alzheimer disease (AD) have aimed to
      reduce the level of toxic forms of A beta peptide in the brain. Here, we directly
      analyze the therapeutic utility of the polyclonal anti-A beta(1-11) antibody
      induced in 3xTg-AD mice vaccinated with the second generation prototype epitope
      vaccine. Substoichiometric concentrations of purified anti-A beta(1-11) antibody
      prevented aggregation of A beta(42) and induced disaggregation of preformed A
      beta(42) fibrils down to nonfilamentous and nontoxic species. Anti-A beta(1-11)
      antibody delayed A beta(42) oligomer formation but ultimately appeared to
      stabilize nonfibrillar conformations, including oligomer-like assemblies. The
      reduced oligomer-mediated cytotoxicity observed upon preincubation of A beta
      oligomers with the anti-A beta(1-11) antibody in the absence of oligomer
      disaggregation suggests a possible oligomer rearrangement in the presence of the
      antibody. These in vitro observations suggest that preventive vaccination may
      protect from AD or may delay the onset of the disease, whereas therapeutic
      vaccination cannot disrupt the toxic oligomers and may only minimally alleviate
      preexisting AD pathology.

PMID- 17545161
TI  - Structure of the Ebola fusion peptide in a membrane-mimetic environment and the
      interaction with lipid rafts.
AB  - The fusion peptide EBO(16) (GAAIGLAWIPYFGPAA) comprises the fusion domain of an
      internal sequence located in the envelope fusion glycoprotein (GP2) of the Ebola
      virus. This region interacts with the cellular membrane of the host and leads to
      membrane fusion. To gain insight into the mechanism of the peptide-membrane
      interaction and fusion, insertion of the peptide was modeled by experiments in
      which the tryptophan fluorescence and (1)H NMR were monitored in the presence of
      sodium dodecyl sulfate micelles or in the presence of detergent-resistant
      membrane fractions. In the presence of SDS micelles, EBO(16) undergoes a random
      coil-helix transition, showing a tendency to self-associate. The three
      dimensional structure displays a 3(10)-helix in the central part of molecule,
      similar to the fusion peptides of many known membrane fusion proteins. Our
      results also reveal that EBO(16) can interact with detergent-resistant membrane
      fractions and strongly suggest that Trp-8 and Phe-12 are important for structure
      maintenance within the membrane bilayer. Replacement of tryptophan 8 with alanine
      (W8A) resulted in dramatic loss of helical structure, proving the importance of
      the aromatic ring in stabilizing the helix. Molecular dynamics studies of the
      interaction between the peptide and the target membrane also corroborated the
      crucial participation of these aromatic residues. The aromatic-aromatic
      interaction may provide a mechanism for the free energy coupling between random
      coil-helical transition and membrane anchoring. Our data shed light on the
      structural "domains" of fusion peptides and provide a clue for the development of
      a drug that might block the early steps of viral infection.

PMID- 17545162
TI  - Use of biotin derivatives to probe conformational changes in proteins.
AB  - Sulfosuccinimidyl-6-(biotinamido) hexanoate and derivatives thereof covalently
      bind to the epsilon-amino group of lysine residues. Our observation that access
      of the biotin derivative to specific lysine residues depends on conformational
      properties of the entire polypeptide chain prompted us to investigate whether
      differential biotinylation patterns of a protein can be used as indicators for
      conformational changes. Bovine serum albumin is a soluble protein with
      characteristic unfolding kinetics upon exposure to high temperature. First, we
      show that biotinylation patterns of proteins are highly reproducible. Second, we
      demonstrate by mass spectrometry and tandem mass spectrometry that unfolding of
      the protein correlates with the accessibility of the biotin derivative to
      specific lysine residues. We have applied this experimental strategy to the
      analysis of a cell-surface protein, viz. the human band 3 anion exchanger of
      erythrocytes infected with the malaria parasite Plasmodium falciparum. We found
      that Lys(826) in a highly flexible loop can be biotinylated in non-infected (but
      not infected) erythrocytes, confirming earlier observations (Winograd, E., and
      Sherman, I. W. (2004) Mol. Biochem. Parasitol. 138, 83-87) based on epitope
      specific monoclonal antibodies suggesting that this region undergoes a
      conformational change upon infection.

PMID- 17545163
TI  - Protein-tyrosine phosphatase 1B deficiency reduces insulin resistance and the
      diabetic phenotype in mice with polygenic insulin resistance.
AB  - Mice heterozygous for insulin receptor (IR) and IR substrate (IRS)-1 deficiency
      provide a model of polygenic type 2 diabetes in which early-onset, genetically
      programmed insulin resistance leads to diabetes. Protein-tyrosine phosphatase 1B
      (PTP1B) dephosphorylates tyrosine residues in IR and possibly IRS proteins,
      thereby inhibiting insulin signaling. Mice lacking PTP1B are lean and have
      increased insulin sensitivity. To determine whether PTP1B can modify polygenic
      insulin resistance, we crossed PTP1B-/- mice with mice with a double heterozygous
      deficiency of IR and IRS-1 alleles (DHet). DHet mice weighed slightly less than
      wild-type mice and exhibited severe insulin resistance and hyperglycemia, with
      approximately 35% of DHet males developing diabetes by 9-10 weeks of age. Body
      weight in DHet mice with PTP1B deficiency was similar to that in DHet mice.
      However, absence of PTP1B in DHet mice markedly improved glucose tolerance and
      insulin sensitivity at 10-11 weeks of age and reduced the incidence of diabetes
      and hyperplastic pancreatic islets at 6 months of age. Insulin-stimulated
      phosphorylation of IR, IRS proteins, Akt/protein kinase B, glycogen synthase
      kinase 3beta, and p70(S6K) was impaired in DHet mouse muscle and liver and was
      differentially improved by PTP1B deficiency. In addition, increased
      phosphoenolpyruvate carboxykinase expression in DHet mouse liver was reversed by
      PTP1B deficiency. In summary, PTP1B deficiency reduces insulin resistance and
      hyperglycemia without altering body weight in a model of polygenic type 2
      diabetes. Thus, even in the setting of high genetic risk for diabetes, reducing
      PTP1B is partially protective, further demonstrating its attractiveness as a
      target for prevention and treatment of type 2 diabetes.

PMID- 17545164
TI  - Two alternative conformations of S-adenosyl-L-homocysteine bound to Escherichia
      coli DNA adenine methyltransferase and the implication of conformational changes
      in regulating the catalytic cycle.
AB  - The crystal structure of the Escherichia coli DNA adenine methyltransferase
      (EcoDam) in a binary complex with the cofactor product S-adenosyl-L-homocysteine
      (AdoHcy) unexpectedly showed the bound AdoHcy in two alternative conformations,
      extended or folded. The extended conformation represents the catalytically
      competent conformation, identical to that of EcoDam-DNA-AdoHcy ternary complex.
      The folded conformation prevents catalysis, because the homocysteine moiety
      occupies the target Ade binding pocket. The largest difference between the binary
      and ternary structures is in the conformation of the N-terminal hexapeptide
      ((9)KWAGGK(14)). Cofactor binding leads to a strong change in the fluorescence of
      Trp(10), whose indole ring approaches the cofactor by 3.3A(.) Stopped-flow
      kinetics and AdoMet cross-linking studies indicate that the cofactor prefers
      binding to the enzyme after preincubation with DNA. In the presence of DNA,
      AdoMet binding is approximately 2-fold stronger than AdoHcy binding. In the
      binary complex the side chain of Lys(14) is disordered, whereas Lys(14)
      stabilizes the active site in the ternary complex. Fluorescence stopped-flow
      experiments indicate that Lys(14) is important for EcoDam binding of the
      extrahelical target base into the active site pocket. This suggests that the
      hexapeptide couples specific DNA binding (Lys(9)), AdoMet binding (Trp(10)), and
      insertion of the flipped target base into the active site pocket (Lys(14)).

PMID- 17545165
TI  - Induction of base damages representing a high risk site for double-strand DNA
      break formation in genomic DNA by exposure of cells to DNA damaging agents.
AB  - DNA repair is known as a defense mechanism against genotoxic insults. However,
      the most lethal type of DNA damages, double-strand DNA breaks (DSBs), can be
      produced by DNA repair. We have previously demonstrated that when long patch base
      excision repair attempts to repair a synthetic substrate containing two uracils,
      the repair produces DSBs (Vispe, S. and Satoh, M. S. (2000) J. Biol. Chem. 275,
      27386-27392 and Vispe, S., Ho, E. L., Yung, T. M., and Satoh, M. S. (2003) J.
      Biol. Chem. 278, 35279-35285). In this synthetic substrate, the two uracils are
      located on the opposite DNA strands (separated by an intervening sequence stable
      at 37 degrees C) and represent a high risk site for DSB formation. It is not
      clear, however, whether similar high risk sites are also induced in genomic DNA
      by exposure to DNA damaging agents. Thus, to investigate the mechanisms of DSB
      formation, we have modified the DSB formation assay developed previously and
      demonstrated that high risk sites for DSB formation are indeed generated in
      genomic DNA by exposure of cells to alkylating agents. In fact, genomic DNA
      containing alkylated base damages, which could represent high risk sites, are
      converted into DSBs by enzymes present in extracts prepared from cells derived
      from clinically normal individuals. Furthermore, DSBs are also produced by
      extracts from cells derived from ataxia-telangiectasia patients who show cancer
      proneness due to an impaired response to DSBs. These results suggest the presence
      of a novel link between base damage formation and DSBs and between long patch
      base excision repair and human diseases that occur due to an impaired response to
      DSB.

PMID- 17545166
TI  - A second proliferating cell nuclear antigen loader complex, Ctf18-replication
      factor C, stimulates DNA polymerase eta activity.
AB  - Replication factor C (RFC) loads the clamp protein PCNA onto DNA structures.
      Ctf18-RFC, which consists of the chromosome cohesion factors Ctf18, Dcc1, and
      Ctf8 and four small RFC subunits, functions as a second proliferating cell
      nuclear antigen (PCNA) loader. To identify potential targets of Ctf18-RFC, human
      cell extracts were assayed for DNA polymerase activity specifically stimulated by
      Ctf18-RFC in conjunction with PCNA. After several chromatography steps, an
      activity stimulated by Ctf18-RFC but not by RFC was identified. Liquid
      chromatography/tandem mass spectrometry (LC/MS/MS) analysis revealed the presence
      of two DNA polymerases, eta and lambda, in the most purified fraction, but
      experiments with purified recombinant proteins demonstrated that only polymerase
      (pol) eta was responsible for activity. Ctf18-RFC alone stimulated pol eta, and
      the addition of PCNA cooperatively increased stimulation. Furthermore, Ctf18-RFC
      interacted physically with pol eta, as indicated by co-precipitation in human
      cells. We propose that this novel loader-DNA polymerase interaction allows DNA
      replication forks to overcome interference by various template structures,
      including damaged DNA and DNA-protein complexes that maintain chromosome
      cohesion.

PMID- 17545167
TI  - Survival factor withdrawal-induced apoptosis of TF-1 cells involves a TRB2-Mcl-1
      axis-dependent pathway.
AB  - Tribbles, an atypical protein kinase superfamily member, coordinates cell
      proliferation, migration, and morphogenesis during the development of Drosophila
      and Xenopus embryos. Although Tribbles are highly conserved throughout evolution,
      the physiological functions of mammalian Tribbles family remain largely unclear.
      Here we report that human TRB2 is a pro-apoptotic molecule that induces apoptosis
      of cells mainly of the hematopoietic origin. TRB2 mRNA is selectively induced by
      removal of granulocyte macrophage colony-stimulating factor (GM-CSF) or
      interleukin-2 from human erythroleukemia-derived TF-1 cell line or activated
      primary CD4(+) T cells, respectively. It is, however, not induced by many other
      treatments that trigger apoptosis of these two cell types. Overexpression of TRB2
      activates many apoptotic events observed in GM-CSF-deprived TF-1 cells, including
      loss of mitochondrial membrane potential, Mcl-1 cleavage/degradation, and
      activation of Bax and a number of caspases. Specific knockdown of TRB2
      significantly suppresses GM-CSF deprivation-induced apoptosis and all apoptotic
      events mentioned above. Finally, we demonstrate that TRB2-induced cleavage and
      degradation of Mcl-1 are mediated via a caspase-dependent but proteasome
      independent mechanism, and overexpression of Mcl-1 or its upstream activator Akt
      can markedly overcome the apoptogenic effect of TRB2. Altogether, these results
      suggest that the TRB2-Mcl-1 axis plays an important role in survival factor
      withdrawal-induced apoptosis of TF-1 cells.

PMID- 17545168
TI  - Chaperone functions of the E3 ubiquitin ligase CHIP.
AB  - The carboxyl terminus of the Hsc70-interacting protein (CHIP) is an Hsp70 co
      chaperone as well as an E3 ubiquitin ligase that protects cells from proteotoxic
      stress. The abilities of CHIP to interact with Hsp70 and function as a ubiquitin
      ligase place CHIP at a pivotal position in the protein quality control system,
      where its entrance into Hsp70-substrate complexes partitions nonnative proteins
      toward degradation. However, the manner by which Hsp70 substrates are selected
      for ubiquitination by CHIP is not well understood. We discovered that CHIP
      possesses an intrinsic chaperone activity that enables it to selectively
      recognize and bind nonnative proteins. Interestingly, the chaperone function of
      CHIP is temperature-sensitive and is dramatically enhanced by heat stress. The
      ability of CHIP to recognize nonnative protein structure may aid in selection of
      slow folding or misfolded polypeptides for ubiquitination.

PMID- 17545169
TI  - Receptor occupancy and channel-opening kinetics: a study of GLUR1 L497Y AMPA
      receptor.
AB  - AMPA glutamate ion channels are tetrameric receptors in which activation to form
      the open channel depends on the binding of possibly multiple glutamate molecules.
      However, it is unclear whether AMPA receptors bound with a different number of
      glutamate molecules (i.e. one being the minimal and four being the maximal number
      of glutamate molecules) open the channels with different kinetic constants. Using
      a laser pulse photolysis technique that provides microsecond time resolution, we
      investigated the channel-opening kinetic mechanism of a nondesensitizing AMPA
      receptor, i.e. GluR1Q(flip) L497Y or a leucine-to-tyrosine substitution mutant,
      in the entire range of glutamate concentrations to ensure receptor saturation. We
      found that the minimal number of glutamate molecules required to bind to the
      receptor and to open the channel is two (or n = 2), and that the entire channel
      opening kinetics can be adequately described by just one channel-opening rate
      constant, k(op), which correlates to n = 2. This result suggests that higher
      receptor occupancy (n = 3 and 4) does not give rise to different k(op) values or,
      at least, not appreciably if the k(op) values are different. Furthermore,
      compared with the wild-type receptor (Li, G., and Niu, L. (2004) J. Biol. Chem.
      279, 3990-3997), the channel-opening and channel-closing rate constants of the
      mutant are 1.5- and 13-fold smaller, respectively. Thus, the major effect of this
      mutation is to decrease the channel-closing rate constant by stabilizing the open
      channel conformation.

PMID- 17545170
TI  - Let's get on with it!

PMID- 17545171
TI  - Invited commentary.

PMID- 17545172
TI  - On "A new evaluation method for lumbar spinal instability..." Kasai et Al. Phys
      Ther. 2006;86:1661-1667.

PMID- 17545173
TI  - What adult nephrologists should know about childhood blood pressure.

PMID- 17545174
TI  - Midazolam vs. diphenhydramine for the treatment of metoclopramide-induced
      akathisia: a randomized controlled trial.
AB  - OBJECTIVES: To compare the effects of midazolam, which is a fast and short-acting
      benzodiazepine, and diphenhydramine, which is a widely used anticholinergic
      agent, in clinical practice for the treatment of metoclopramide-induced
      akathisia. METHODS: All adults older than 17 years given metoclopramide for
      nausea and vomiting or for headache and who had akathisia were eligible for this
      clinical, randomized, double-blind trial. Patients were randomized to receive
      diphenhydramine or midazolam. Subjective, objective, and total akathisia scores
      and modified Ramsay Sedation Scale scores were recorded. Repeated-measures
      analysis of variance was used to compare the efficacy and side effects of the
      medications. RESULTS: Forty-one (73.3%) of the 56 enrolled patients were women.
      The mean (+/-SD) age was 39.9 (+/-15.7) years in the diphenhydramine group and
      40.9 (+/-16.2) years in the midazolam group. Mean subjective, objective, and
      total akathisia scores in the first 5 minutes declined considerably in the
      midazolam group compared with the diphenhydramine group (p < 0.001). However, the
      mean Ramsay Sedation Scale score in the first 15 minutes increased significantly
      in the midazolam group compared with the diphenhydramine group (p < 0.001).
      CONCLUSIONS: Midazolam can correct the symptoms of metoclopramide-induced
      akathisia faster than diphenhydramine, but it causes more sedation.

PMID- 17545175
TI  - Using archaeal histones for precise DNA fragmentation.
AB  - The fragmentation of DNA is a useful procedure for many molecular biology
      procedures. However, most methods used to fragment DNA are poorly controllable,
      and cannot be used to create small fragments. We describe a method to generate
      random DNA fragments of a predictable size to be cloned in expression vectors for
      the construction of display libraries. The DNA is allowed to form complexes with
      archaeal histones from Methanothermus fervidus (HMf) and the HMf/DNA core complex
      is naturally protected from nuclease DNaseI activity, giving rise to DNA
      fragments of approximately 60 bp and multiples thereof. We found that by varying
      the wt/wt ratio between DNA and HMf, the concentration of DNA and the incubation
      time with DNaseI, DNA fragments of desired size can be obtained. This approach
      should be applicable to the efficient fragmentation of DNA for the construction
      of phage display polypeptide libraries, as well as any other molecular biology
      procedures in which small DNA fragments of defined size are required.

PMID- 17545176
TI  - Histoplasmosis in a child with JRA on low-dose methotrexate.

PMID- 17545177
TI  - POODLE-L: a two-level SVM prediction system for reliably predicting long
      disordered regions.
AB  - MOTIVATION: Recent experimental and theoretical studies have revealed several
      proteins containing sequence segments that are unfolded under physiological
      conditions. These segments are called disordered regions. They are actively
      investigated because of their possible involvement in various biological
      processes, such as cell signaling, transcriptional and translational regulation.
      Additionally, disordered regions can represent a major obstacle to high
      throughput proteome analysis and often need to be removed from experimental
      targets. The accurate prediction of long disordered regions is thus expected to
      provide annotations that are useful for a wide range of applications. RESULTS: We
      developed Prediction Of Order and Disorder by machine LEarning (POODLE-L; L
      stands for long), the Support Vector Machines (SVMs) based method for predicting
      long disordered regions using 10 kinds of simple physico-chemical properties of
      amino acid. POODLE-L assembles the output of 10 two-level SVM predictors into a
      final prediction of disordered regions. The performance of POODLE-L for
      predicting long disordered regions, which exhibited a Matthew's correlation
      coefficient of 0.658, was the highest when compared with eight well-established
      publicly available disordered region predictors. AVAILABILITY: POODLE-L is freely
      available at http://mbs.cbrc.jp/poodle/poodle-l.html. SUPPLEMENTARY INFORMATION:
      Supplementary data are available at Bioinformatics online.

PMID- 17545178
TI  - BioText Search Engine: beyond abstract search.
AB  - The BioText Search Engine is a freely available Web-based application that
      provides biologists with new ways to access the scientific literature. One novel
      feature is the ability to search and browse article figures and their captions. A
      grid view juxtaposes many different figures associated with the same keywords,
      providing new insight into the literature. An abstract/title search and list view
      shows at a glance many of the figures associated with each article. The interface
      is carefully designed according to usability principles and techniques. The
      search engine is a work in progress, and more functionality will be added over
      time. AVAILABILITY: http://biosearch.berkeley.edu.

PMID- 17545179
TI  - PIP: a database of potential intron polymorphism markers.
AB  - MOTIVATION: With the recent progress made in large-scale plant functional genome
      sequencing projects, a great amount of EST (express sequence tag) data is
      becoming available. With the help of complete genomic sequence information of
      model plants (rice and Arabidopsis), it is possible to predict the joints between
      adjacent exons after splicing (or termed 'intron positions' for short) in
      homologous ESTs of other plants. This would allow developing potential intron
      polymorphism (PIP) markers in these plants by designing primers in exons flanking
      the target intron. RESULTS: We have extracted a total of 57,658 PIP markers in 59
      plant species and created a web-based database platform named PIP to provide
      detailed information of these PIP markers and homologous relationships among PIP
      markers from different species. The platform also provides a function of online
      designing of PIP markers based on cDNA/EST sequences submitted by users. With
      evaluations performed in silico, we have found that the intron position
      prediction is highly reliable and the polymorphism level of PIP markers is high
      enough for practical need. AVAILABILITY: http://ibi.zju.edu.cn/pgl/pip/.
      SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics
      online.

PMID- 17545180
TI  - OMA Browser--exploring orthologous relations across 352 complete genomes.
AB  - MOTIVATION: Inference of the evolutionary relation between proteins, in
      particular the identification of orthologs, is a central problem in comparative
      genomics. Several large-scale efforts with various methodologies and scope tackle
      this problem, including OMA (the Orthologous MAtrix project). RESULTS: Based on
      the results of the OMA project, we introduce here the OMA Browser, a web-based
      tool allowing the exploration of orthologous relations over 352 complete genomes.
      Orthologs can be viewed as groups across species, but also at the level of
      sequence pairs, allowing the distinction among one-to-one, one-to-many and many
      to-many orthologs. AVAILABILITY: http://omabrowser.org.

PMID- 17545181
TI  - Edge-based scoring and searching method for identifying condition-responsive
      protein-protein interaction sub-network.
AB  - MOTIVATION: Current high-throughput protein-protein interaction (PPI) data do not
      provide information about the condition(s) under which the interactions occur.
      Thus, the identification of condition-responsive PPI sub-networks is of great
      importance for investigating how a living cell adapts to changing environments.
      RESULTS: In this article, we propose a novel edge-based scoring and searching
      approach to extract a PPI sub-network responsive to conditions related to some
      investigated gene expression profiles. Using this approach, what we constructed
      is a sub-network connected by the selected edges (interactions), instead of only
      a set of vertices (proteins) as in previous works. Furthermore, we suggest a
      systematic approach to evaluate the biological relevance of the identified
      responsive sub-network by its ability of capturing condition-relevant functional
      modules. We apply the proposed method to analyze a human prostate cancer dataset
      and a yeast cell cycle dataset. The results demonstrate that the edge-based
      method is able to efficiently capture relevant protein interaction behaviors
      under the investigated conditions. SUPPLEMENTARY INFORMATION: Supplementary data
      are available at Bioinformatics online.

PMID- 17545182
TI  - VIPER: an advanced software package to support high-throughput LC-MS peptide
      identification.
AB  - SUMMARY: The accurate mass and time (AMT) tag approach is used for analysis of
      large scale experiments by combining information generated over multiple datasets
      and instrument types. The VIPER software package is one of the key components of
      the data processing pipeline and implements automated algorithms to discover LC
      MS features, align and match these LC-MS features to a database of peptides
      previously identified in LC-MS/MS analyses, and identify and quantify pairs of
      isotopically labeled peptides. AVAILABILITY: VIPER may be downloaded free of
      charge at http://ncrr.pnl.gov/software/

PMID- 17545183
TI  - OBO-Edit--an ontology editor for biologists.
AB  - OBO-Edit is an open source, platform-independent ontology editor developed and
      maintained by the Gene Ontology Consortium. Implemented in Java, OBO-Edit uses a
      graph-oriented approach to display and edit ontologies. OBO-Edit is particularly
      valuable for viewing and editing biomedical ontologies. AVAILABILITY:
      https://sourceforge.net/project/showfiles.php?group_id=36855.

PMID- 17545184
TI  - Limitations of rapid HIV-1 tests during screening for trials in Uganda:
      diagnostic test accuracy study.
AB  - OBJECTIVE: To evaluate the limitations of rapid tests for HIV-1. DESIGN:
      Diagnostic test accuracy study. SETTING: Rural Rakai, Uganda. PARTICIPANTS: 1517
      males aged 15-49 screened for trials of circumcision for HIV prevention. MAIN
      OUTCOME MEASURES: Sensitivity, specificity, negative predictive values, and
      positive predictive values of an algorithm using three rapid tests for HIV,
      compared with the results of enzyme immunoassay and western blotting as the
      optimal methods. RESULTS: Rapid test results were evaluated by enzyme immunoassay
      and western blotting. Sensitivity was 97.7%. Among 639 samples where the strength
      of positive bands was coded if the sample showed positivity for HIV, the
      algorithm had low specificity (94.1%) and a low positive predictive value
      (74.0%). Exclusion of 37 samples (5.8%) with a weak positive band improved the
      specificity (99.6%) and positive predictive value (97.7%). CONCLUSION: Weak
      positive bands on rapid tests for HIV should be confirmed by enzyme immunoassay
      and western blotting before disclosing the diagnosis. Programmes using rapid
      tests routinely should use standard serological assays for quality control. Trial
      registration Clinical Trials NCT00425984.

PMID- 17545185
TI  - Long term results of compression therapy alone versus compression plus surgery in
      chronic venous ulceration (ESCHAR): randomised controlled trial.
AB  - OBJECTIVE: To determine whether recurrence of leg ulcers may be prevented by
      surgical correction of superficial venous reflux in addition to compression.
      DESIGN: Randomised controlled trial. SETTING: Specialist nurse led leg ulcer
      clinics in three UK vascular centres. PARTICIPANTS: 500 patients (500 legs) with
      open or recently healed leg ulcers and superficial venous reflux. INTERVENTIONS:
      Compression alone or compression plus saphenous surgery. MAIN OUTCOME MEASURES:
      Primary outcomes were ulcer healing and ulcer recurrence. The secondary outcome
      was ulcer free time. RESULTS: Ulcer healing rates at three years were 89% for the
      compression group and 93% for the compression plus surgery group (P=0.73, log
      rank test). Rates of ulcer recurrence at four years were 56% for the compression
      group and 31% for the compression plus surgery group (P<0.01). For patients with
      isolated superficial reflux, recurrence rates at four years were 51% for the
      compression group and 27% for the compress plus surgery group (P<0.01). For
      patients who had superficial with segmental deep reflux, recurrence rates at
      three years were 52% for the compression group and 24% for the compression plus
      surgery group (P=0.04). For patients with superficial and total deep reflux,
      recurrence rates at three years were 46% for the compression group and 32% for
      the compression plus surgery group (P=0.33). Patients in the compression plus
      surgery group experienced a greater proportion of ulcer free time after three
      years compared with patients in the compression group (78% v 71%; P=0.007, Mann
      Whitney U test). CONCLUSION: Surgical correction of superficial venous reflux in
      addition to compression bandaging does not improve ulcer healing but reduces the
      recurrence of ulcers at four years and results in a greater proportion of ulcer
      free time. TRIAL REGISTRATION: Current Controlled Trials ISRCTN07549334
      [controlled-trials.com].

PMID- 17545186
TI  - Context dependence, ancestral misidentification, and spurious signatures of
      natural selection.
AB  - Population genetic analyses often use polymorphism data from one species, and
      orthologous genomic sequences from closely related outgroup species. These
      outgroup sequences are frequently used to identify ancestral alleles at
      segregating sites and to compare the patterns of polymorphism and divergence.
      Inherent in such studies is the assumption of parsimony, which posits that the
      ancestral state of each single nucleotide polymorphism (SNP) is the allele that
      matches the orthologous site in the outgroup sequence, and that all nucleotide
      substitutions between species have been observed. This study tests the effect of
      violating the parsimony assumption when mutation rates vary across sites and over
      time. Using a context-dependent mutation model that accounts for elevated
      mutation rates at CpG dinucleotides, increased propensity for transitional versus
      transversional mutations, as well as other directional and contextual mutation
      biases estimated along the human lineage, we show (using both simulations and a
      theoretical model) that enough unobserved substitutions could have occurred since
      the divergence of human and chimpanzee to cause many statistical tests to
      spuriously reject neutrality. Moreover, using both the chimpanzee and rhesus
      macaque genomes to parsimoniously identify ancestral states causes a large
      fraction of the data to be removed while not completely alleviating problem. By
      constructing a novel model of the context-dependent mutation process, we can
      correct polymorphism data for the effect of ancestral misidentification using a
      single outgroup.

PMID- 17545187
TI  - Contribution of horizontally acquired genomic islands to the evolution of the
      tubercle bacilli.
AB  - The contribution of horizontal gene transfer (HGT) to the evolution of
      Mycobacterium tuberculosis -- the main causal agent of tuberculosis in humans --
      and closely related members of the M. tuberculosis complex remains poorly
      understood. Using a combination of genome-wide parametric analyses, we have
      identified 48 M. tuberculosis chromosomal regions with atypical characteristics,
      potentially due to HGT. These specific regions account for 4.5% of the genome
      (199 kb) and include 256 genes. Many display features typical of the genomic
      islands found in other bacteria, including residual material from mobile genetic
      elements, flanking direct repeats, insertion in the vicinity of tRNA sequences,
      and genes with putative or documented virulence functions. Southern blotting
      analysis of nine of these 48 regions confirmed their presence in "Mycobacterium
      prototuberculosis," the ancestral species of the M. tuberculosis complex.
      Finally, our results strongly suggest that the ancestor of the tubercle bacilli
      was an environmental bacillus that exchanged genetic material with other
      bacterial species, including Proteobacteria in particular, present in its
      surroundings. This study describes a rational approach to searching for
      mycobacterial virulence genes, and highlights the importance of dissecting gene
      transfer networks to improve our understanding of mycobacterial pathogenicity and
      evolution.

PMID- 17545188
TI  - Adaptation of HIV-1 to its human host.
AB  - Human immunodeficiency virus type 1 (HIV-1) originated from three independent
      cross-species transmissions of simian immunodeficiency virus (SIVcpzPtt)
      infecting chimpanzees (Pan troglodytes troglodytes) in west central Africa,
      giving rise to pandemic (group M) and non-pandemic (groups N and O) clades of HIV
      1. To identify host-specific adaptations in HIV-1 we compared the inferred
      ancestral sequences of HIV-1 groups M, N and O to 12 full length genome sequences
      of SIVcpzPtt and four of the outlying but closely related SIVcpzPts (from P. t.
      schweinfurthii). This analysis revealed a single site that was completely
      conserved among SIVcpzPtt strains but different (due to the same change) in all
      three groups of HIV-1. This site, Gag-30, lies within p17, the gag-encoded matrix
      protein. It is Met in SIVcpzPtt, underwent a conservative replacement by Leu in
      one lineage of SIVcpzPts but changed radically to Arg on all three lineages
      leading to HIV-1. During subsequent diversification this site has been conserved
      as a basic residue (Arg or Lys) in most lineages of HIV-1. Retrospective analysis
      revealed that Gag-30 had reverted to Met in a previous experiment in which HIV-1
      was passaged through chimpanzees. To examine whether this substitution conferred
      a species specific growth advantage, we used site-directed mutagenesis to
      generate variants of these chimpanzee-adapted HIV-1 strains with Lys at Gag-30,
      and tested their replication in both human and chimpanzee CD4+ T lymphocytes.
      Remarkably, viruses encoding Met replicated to higher titers than viruses
      encoding Lys in chimpanzee T cells, but the opposite was found in human T cells.
      Taken together, these observations provide compelling evidence for host-specific
      adaptation during the emergence of HIV-1 and identify the viral matrix protein as
      a modulator of viral fitness following transmission to the new human host.

PMID- 17545189
TI  - The relationship between cancer and medication exposures in systemic lupus
      erythaematosus: a case-cohort study.
AB  - OBJECTIVE: To examine if, in systemic lupus erythaematosus (SLE), exposure to
      immunosuppressive therapy (cyclophosphamide, azathioprine, methotrexate)
      increases cancer risk. METHODS: A case-cohort study was performed within a multi
      site international SLE cohort; subjects were linked to regional tumour registries
      to determine cancer cases occurring after entry into the cohort. We calculated
      the hazard ratio (HR) for cancer after exposure to an immunosuppressive drug, in
      models that controlled for other medications (anti-malarial drugs, systemic
      glucocorticoids, non-steroidal anti-inflammatory drugs (NSAIDs), aspirin),
      smoking, age, sex, race/ethnicity, geographic location, calendar year, SLE
      duration, and lupus damage scores. In the primary analyses, exposures were
      treated categorically (ever/never) and as time-dependent. RESULTS: Results are
      presented from 246 cancer cases and 538 controls without cancer. The adjusted HR
      for overall cancer risk after any immunosuppressive drug was 0.82 (95% CI 0.50
      1.36). Age > or = 65, and the presence of non-malignancy damage were associated
      with overall cancer risk. For lung cancer (n = 35 cases), smoking was also a
      prominent risk factor. When looking at haematological cancers specifically (n =
      46 cases), there was a suggestion of an increased risk after immunosuppressive
      drug exposures, particularly when these were lagged by a period of 5 years
      (adjusted HR 2.29, 95% CI 1.02-5.15). CONCLUSIONS: In our SLE sample, age > or =
      65, damage, and tobacco exposure were associated with cancer risk. Though
      immunosuppressive therapy may not be the principal driving factor for overall
      cancer risk, it may contribute to an increased risk of haematological
      malignancies. Future studies are in progress to evaluate independent influence of
      medication exposures and disease activity on risk of malignancy.

PMID- 17545190
TI  - P-selectin glycoprotein ligand-1 VNTR polymorphisms and risk of thrombosis in the
      antiphospholipid syndrome.
AB  - OBJECTIVES: Antiphospholipid antibodies (aPLA) have been shown to enhance
      thrombus formation by increasing the expression of adhesive receptors such as P
      selectin on endothelial cells. The P-selectin counter-receptor on leucocytes is P
      selectin glycoprotein ligand-1 (PSGL-1). We have previously described a variable
      number of tandem repeats (VNTR) polymorphism in the mucin-like region of PSGL-1,
      with three alleles: allele A, 16 repeats; allele B, 15 repeats; and allele C, 14
      repeats. METHODS: We compared the PSGL-1 VNTR allele and genotype frequencies in
      90 patients with antiphospholipid syndrome (APS) with thrombosis, 39 patients
      with persistent aPLA positivity without thrombosis, and 203 healthy controls.
      RESULTS: The frequency of the B allele was significantly higher in patients with
      APS with thrombosis compared with patients without thrombosis (p = 0.023). When
      we compared the groups by genotype frequencies, we found a markedly higher
      frequency of the AB genotype in patients with APS with thrombosis than in aPLA
      positive patients without thrombosis (38.9% vs 10.3%, p = 0.001) or in normal
      population (38.9% vs 22.2%, p<0.01). CONCLUSIONS: We suggest that the VNTR
      polymorphism of PSGL-1 is a significant determinant of thrombotic predisposition
      in patients with APS. Furthermore, risk appears to correlate best with the
      combination of alleles inherited rather than with the presence of any particular
      allele.

PMID- 17545192
TI  - Intracellular localisation of galectin-3 has a protective role in chondrocyte
      survival.
AB  - OBJECTIVE: Although galectin-3 (gal-3) is expressed during arthritic disorders,
      the part it plays has never been described. The aim of the study was to determine
      the intracellular roles of gal-3 in chondrocytes and cartilage. METHODS:
      Following treatment with sodium nitroprusside, a cell death inducer,
      intracellular levels of total and phosphorylated gal-3 were measured by
      immunoblots in human osteoarthritic (OA) chondrocytes. Cell viability was also
      assessed by the lactate dehydrogenase activity in conditioned media from OA
      chondrocytes or from ATDC5 cells transfected with a gal-3-expressing vector.
      After generating an OA model by intra-articular injection of 0.5% mono
      iodoacetate (MIA), histological evaluation of articular cartilage and subchondral
      bone was performed in wild-type (WT) and gal-3 knockout (KO) mice aged 6 weeks
      and 4 months. RESULTS: In vitro experiments demonstrated that intracellular gal-3
      had a protective role in chondrocyte survival, which involved its
      phosphorylation. In contrast to 6-week-old mice, 4-month-old gal-3 KO mice,
      compared with WT mice, presented OA-like cartilage modifications. OA induction
      via MIA injection in WT mice generated cartilage lesions similar to those found
      in gal-3 KO animals. Moreover, OA induction showed a significant decrease in
      subchondral bone surface in the gal-3 KO mice in contrast to the WT group.
      CONCLUSIONS: Altogether these findings indicate that intracellular gal-3 has a
      beneficial effect in articular cells, as its absence in KO mice led to cartilage
      lesions.

PMID- 17545191
TI  - Differential expression of syndecans and glypicans in chronically inflamed
      synovium.
AB  - BACKGROUND: Membrane-bound heparan sulphate proteoglycans (HSPGs) act as co
      receptors and presenters of cytokines and are involved in cell-matrix and cell
      cell adhesion. AIM: To investigate which HSPGs are expressed in knee joint
      synovia from patients with different forms of arthritis and normal individuals.
      METHODS: Synovial samples were obtained from patients with early rheumatoid
      arthritis (n = 8), longstanding rheumatoid arthritis (n = 13), psoriatic
      arthritis (n = 7), osteoarthritis (n = 6) and normal joints (n = 12). Expression
      of syndecan-1, -2, -3 and -4 and glypican-1, -3 and -4 was analysed by
      immunohistochemistry and dual label immunofluorescence. RESULTS: The expression
      of HSPGs in chronically inflamed synovium exhibited a differential distribution.
      Syndecan-1 was present in the mononuclear infiltrates of synovia from patients
      with rheumatoid and psoriatic arthritis where it was expressed by plasma cells.
      Syndecan-2 was present mainly in blood vessels where it occurred on endothelial
      cells, pericytes and smooth muscle cells. Syndecan-3 stained intensely in
      endothelial cells but also occurred in sublining macrophages and the lining
      layer. Glypican-4 occurred in the lining layer and blood vessels. Increased
      expression of these HSPGs was apparent in rheumatoid and psoriatic compared to
      osteoarthritic and normal synovia. Little or no staining for syndecan-4, glypican
      1 and glypican-3 was seen in all samples. DISCUSSION: Selected HSPGs, such as
      syndecan-1, -2 and -3 and glypican-4, could play a part in the pathophysiology of
      arthritis, such as the migration and retention of leukocytes and angiogenesis in
      the chronically inflamed synovium.

PMID- 17545193
TI  - Effect of dehydroepiandrosterone administration on fatigue, well-being, and
      functioning in women with primary Sjogren syndrome: a randomised controlled
      trial.
AB  - OBJECTIVE: Dehydroepiandrosterone (DHEA) administration has been reported to
      improve fatigue, psychological distress, and physical disability. These are
      common features of primary Sjogren syndrome (pSS). We investigated the effects of
      DHEA administration on fatigue, well-being, and functioning in women with pSS.
      METHODS: In a double-blind, randomised placebo-controlled clinical trial, 60
      female patients with pSS received 200 mg oral DHEA or placebo. Primary outcome
      measures were general fatigue, depressive mood, mental well-being, and physical
      functioning. In addition, pain, sicca complaints and disease activity parameters
      were measured. Patients were assessed before treatment, after 3, 6, and 12 months
      on study medication, and 6 months after cessation of treatment. RESULTS: Patients
      from both the DHEA- and placebo-treated group improved on general fatigue
      (p<0.001), mental well-being (p = 0.04), and depressive mood (p = 0.008).
      Physical functioning did not change (p = 0.44). Of the secondary outcome
      variables, complaints of a dry mouth diminished during treatment in both groups
      (p = 0.006), the erythrocyte sedimentation rate showed a decrease for the DHEA
      group (p = 0.02), and complaints of dry eyes improved in the placebo group (p =
      0.01). The belief to have used DHEA was a stronger predictor for improvement of
      fatigue and well-being than the actual use of DHEA. CONCLUSIONS: Our study does
      not support a superior effect of DHEA over placebo in female patients with pSS.
      Both DHEA and placebo induce improvement of fatigue and well-being. This may
      suggest possibilities for cognitive behavioural interventions.

PMID- 17545194
TI  - Cross-species microarray analysis with the OSCAR system suggests an INSR->Pax6
      >NQO1 neuro-protective pathway in aging and Alzheimer's disease.
AB  - OSCAR is a web platform for cluster and cross-species analysis of microarray
      data. It provides a comprehensive but friendly environment to both users and
      algorithm developers. For users, OSCAR provides cluster tools for both single and
      multiple species data, together with interactive analysis features. For single
      species data, OSCAR currently provides Hierarchical Clustering, K-means,
      partition around medoids (PAM), Self-Organizing Map (SOM), Tight Clustering and a
      novel algorithm called 'Consensus Tight-clustering'. The new Consensus Tight
      clustering algorithm delivers robust gene clusters and its result is more
      resistant to false positives than other state-of-the-art algorithms. For cross
      species data analysis, OSCAR provides two novel computational tools:
      'coherentCluster', 'coherentSubset' and a novel visualization tool: 'comparative
      heatmap'. Applying the coherentCluster algorithm to human and fly aging data, we
      identified several coherent clusters of genes, which share co-regulation patterns
      that are highly correlated with the aging process in both of the two species. One
      coherent cluster suggests insulin receptor (INSR) may regulate Pax6 in both
      species and across different tissues. Further analysis with human brain
      expression and pathological data suggests an INSR->Pax6->quinone oxidoreductase
      (NQO1)->detoxification neuro-protective pathway might be present in aging or
      diseased brain. For algorithm developers, OSCAR is a plug-and-play platform. With
      little effort, developers can plug their own algorithms into the OSCAR server
      without revealing the source codes, which will equip their command line
      executables with user-friendly interface and interactive analysis capability. In
      summary, OSCAR initiates an open platform for development and application of
      clustering and cross-species analysis programs. OSCAR stands for an open system
      for cluster analysis of microarray data. It is available at:
      http://biocomp.bioen.uiuc.edu/oscar.

PMID- 17545195
TI  - s-RT-MELT for rapid mutation scanning using enzymatic selection and real time DNA
      melting: new potential for multiplex genetic analysis.
AB  - The rapidly growing understanding of human genetic pathways, including those that
      mediate cancer biology and drug response, leads to an increasing need for
      extensive and reliable mutation screening on a population or on a single patient
      basis. Here we describe s-RT-MELT, a novel technology that enables highly
      expanded enzymatic mutation scanning in human samples for germline or low-level
      somatic mutations, or for SNP discovery. GC-clamp-containing PCR products from
      interrogated and wild-type samples are hybridized to generate mismatches at the
      positions of mutations over one or multiple sequences in-parallel. Mismatches are
      converted to double-strand breaks using a DNA endonuclease (Surveyor) and
      oligonucleotide tails are enzymatically attached at the position of mutations. A
      novel application of PCR enables selective amplification of mutation-containing
      DNA fragments. Subsequently, melting curve analysis, on conventional or nano
      technology real-time PCR platforms, detects the samples that contain mutations in
      a high-throughput and closed-tube manner. We apply s-RT-MELT in the screening of
      p53 and EGFR mutations in cell lines and clinical samples and demonstrate its
      advantages for rapid, multiplexed mutation scanning in cancer and for genetic
      variation screening in biology and medicine.

PMID- 17545196
TI  - GeneHub-GEPIS: digital expression profiling for normal and cancer tissues based
      on an integrated gene database.
AB  - GeneHub-GEPIS is a web application that performs digital expression analysis in
      human and mouse tissues based on an integrated gene database. Using aggregated
      expressed sequence tag (EST) library information and EST counts, the application
      calculates the normalized gene expression levels across a large panel of normal
      and tumor tissues, thus providing rapid expression profiling for a given gene.
      The backend GeneHub component of the application contains pre-defined gene
      structures derived from mRNA transcript sequences from major databases and
      includes extensive cross references for commonly used gene identifiers. ESTs are
      then linked to genes based on their precise genomic locations as determined by
      GMAP. This genome-based approach reduces incorrect matches between ESTs and
      genes, thus minimizing the noise seen with previous tools. In addition, the gene
      centric design makes it possible to add several important features, including
      text searching capabilities, the ability to accept diverse input values,
      expression analysis for microRNAs, basic gene annotation, batch analysis and
      linking between mouse and human genes. GeneHub-GEPIS is available at
      http://www.cgl.ucsf.edu/Research/genentech/genehub-gepis/ or
      http://www.gepis.org/.

PMID- 17545197
TI  - ESTExplorer: an expressed sequence tag (EST) assembly and annotation platform.
AB  - The analysis of expressed sequence tag (EST) datasets offers a rapid and cost
      effective approach to elucidate the transcriptome of an organism, but requiring
      several computational methods for assembly and annotation. ESTExplorer is a
      comprehensive workflow system for EST data management and analysis. The pipeline
      uses a 'distributed control approach' in which the most appropriate
      bioinformatics tools are implemented over different dedicated processors. Species
      specific repeat masking and conceptual translation are in-built. ESTExplorer
      accepts a set of ESTs in FASTA format which can be analysed using programs
      selected by the user. After pre-processing and assembly, the dataset is annotated
      at the nucleotide and protein levels, following conceptual translation. Users may
      optionally provide ESTExplorer with assembled contigs for annotation purposes.
      Functionally annotated contigs/ESTs can be analysed individually. The overall
      outputs are gene ontologies, protein functional identifications in terms of
      mapping to protein domains and metabolic pathways. ESTExplorer has been applied
      successfully to annotate large EST datasets from parasitic nematodes and to
      identify novel genes as potential targets for parasite intervention. ESTExplorer
      runs on a Linux cluster and is freely available for the academic community at
      http://estexplorer.biolinfo.org.

PMID- 17545198
TI  - Efficient and exclusive induction of Tet repressor by the oligopeptide Tip
      results from co-variation of their interaction site.
AB  - Protein-protein interactions are an important element of signal transfer within
      and between organisms. They are mainly mediated by short oligopeptide motifs and
      represent a widely used alternative to small, organic molecules for conveying
      information. The transcription factor TetR, a regulator of tetracycline
      resistance in Gram-negative bacteria, is naturally induced by tetracycline or its
      derivatives. The oligopeptide Tip (Transcription inducing peptide) fused to
      either N- or C-terminus of Thioredoxin A (TrxA) has been isolated as an
      artificial inducer for TetR in Escherichia coli. This inducing property can be
      exploited to monitor the in vivo expression of a protein of interest by fusing
      Tip to its C-terminus. We improve the induction efficiency of Tip by adding an
      aromatic amino acid before residue 1 of Tip in C-terminal fusions to TrxA. The
      induction efficiency of that modified TrxA-Tip fusion is further enhanced when
      the effector-binding pocket of TetR is enlarged by the N82A and F86A mutations.
      The double mutant is also insensitive to induction by tetracyclines. Thus, Tip is
      an exclusive inducer of this TetR variant, representing the first example of
      fully converting a small molecular weight effector-dependent transcription factor
      into one depending solely on protein-protein recognition.

PMID- 17545199
TI  - FLAN: a web server for influenza virus genome annotation.
AB  - FLAN (short for FLu ANnotation), the NCBI web server for genome annotation of
      influenza virus (http://www.ncbi.nlm.nih.gov/genomes/FLU/Database/annotation.cgi)
      is a tool for user-provided influenza A virus or influenza B virus sequences. It
      can validate and predict protein sequences encoded by an input flu sequence. The
      input sequence is BLASTed against a database containing influenza sequences to
      determine the virus type (A or B), segment (1 through 8) and subtype for the
      hemagglutinin and neuraminidase segments of influenza A virus. For each
      segment/subtype of the viruses, a set of sample protein sequences is maintained.
      The input sequence is then aligned against the corresponding protein set with a
      'Protein to nucleotide alignment tool' (ProSplign). The translated product from
      the best alignment to the sample protein sequence is used as the predicted
      protein encoded by the input sequence. The output can be a feature table that can
      be used for sequence submission to GenBank (by Sequin or tbl2asn), a GenBank flat
      file, or the predicted protein sequences in FASTA format. A message showing the
      length of the input sequence, the predicted virus type, segment and subtype for
      the hemagglutinin and neuraminidase segments of Influenza A virus will also be
      displayed.

PMID- 17545200
TI  - MyHits: improvements to an interactive resource for analyzing protein sequences.
AB  - The MyHits web site (http://myhits.isb-sib.ch) is an integrated service dedicated
      to the analysis of protein sequences. Since its first description in 2004, both
      the user interface and the back end of the server were improved. A number of
      tools (e.g. MAFFT, Jacop, Dotlet, Jalview, ESTScan) were added or updated to
      improve the usability of the service. The MySQL schema and its associated API
      were revamped and the database engine (HitKeeper) was separated from the web
      interface. This paper summarizes the current status of the server, with an
      emphasis on the new services.

PMID- 17545201
TI  - MinActionPath: maximum likelihood trajectory for large-scale structural
      transitions in a coarse-grained locally harmonic energy landscape.
AB  - The non-linear problem of simulating the structural transition between two known
      forms of a macromolecule still remains a challenge in structural biology. The
      problem is usually addressed in an approximate way using 'morphing' techniques,
      which are linear interpolations of either the Cartesian or the internal
      coordinates between the initial and end states, followed by energy minimization.
      Here we describe a web tool that implements a new method to calculate the most
      probable trajectory that is exact for harmonic potentials; as an illustration of
      the method, the classical Calpha-based Elastic Network Model (ENM) is used both
      for the initial and the final states but other variants of the ENM are also
      possible. The Langevin equation under this potential is solved analytically using
      the Onsager and Machlup action minimization formalism on each side of the
      transition, thus replacing the original non-linear problem by a pair of linear
      differential equations joined by a non-linear boundary matching condition. The
      crossover between the two multidimensional energy curves around each state is
      found numerically using an iterative approach, producing the most probable
      trajectory and fully characterizing the transition state and its energy. Jobs
      calculating such trajectories can be submitted on-line at:
      http://lorentz.dynstr.pasteur.fr/joel/index.php.

PMID- 17545202
TI  - RTAnalyzer: a web application for finding new retrotransposons and detecting L1
      retrotransposition signatures.
AB  - Mobile genetic elements have significantly contributed to the shaping of
      mammalian genomes. The RTAnalyzer software tracks sequences of retrotransposed
      origin by scoring the signature results from an L1-mediated insertion within a
      genome. More specifically, a sequence of interest is searched for in genomic
      databases using BLAST. Each hit, along with additional 5' and 3' sequences of pre
      defined lengths, is saved. RTAnalyzer searches for specific L1 retrotransposition
      signatures (i.e. target site duplication, endonuclease cleavage site and
      poly(A)), and then calculates an overall retrotransposition score. This score
      represents the likelihood of a given sequence originating from a
      retrotransposition event involving the L1 machinery. RTAnalyzer may be used under
      GNU public license, and is available at http://www.riboclub.org/rtanalyzer.

PMID- 17545203
TI  - More physician consultations and antibiotic prescriptions in families with high
      concern about infectious illness--adequate response to infection-prone child or
      self-fulfilling prophecy?
AB  - BACKGROUND: Respiratory tract infections (RTI) in children is the most common
      cause of prescription of antibiotics. It is important to describe and analyse non
      medical factors in order to develop more rational use of antibiotics. OBJECTIVES:
      To compare families with high and low concern about infectious illness with
      regard to social variables, perception of infection proneness and beliefs in
      antibiotics and to relate the concern for infectious illness to reported
      morbidity, physician consultations and antibiotic prescriptions for the 18-month
      old child in the family. METHODS: A prospective, population-based survey was
      performed. During 1 month, all infectious symptoms, physician consultations and
      antibiotic treatments for 18-month-old children were noted. The 818 families also
      answered questions about their socio-economic situation, illness perception and
      concern about infectious illness. RESULTS: High concern about infectious illness
      was associated with more frequent physicians consultations and more prescriptions
      of antibiotics. There was no significant difference in reported days with
      symptoms of RTI, but the parents more often experienced their children with RTI
      without fever as being ill. The variables of infection proneness in the child,
      inadequate beliefs in antibiotics and the factor of being the only child were
      important explanatory factors for concern about infectious illness. CONCLUSIONS:
      High concern about infectious illness is an important determining factor for
      physician consultations and antibiotic prescription for small children. An
      adequate consultation, where the doctor deals with the parents' worries and gives
      appropriate information about symptoms and disease, might contribute to less
      antibiotic prescribing with preserved parental satisfaction.

PMID- 17545204
TI  - Deconstructing psychosis.

PMID- 17545205
TI  - Will undergraduate geriatric medicine survive?

PMID- 17545206
TI  - Post-acute transfer of older people to intermediate care services: the sooner the
      better?

PMID- 17545207
TI  - Application of the voluntary step execution test to identify elderly fallers.
AB  - OBJECTIVES: To assess the use of the Voluntary Step Execution Test to identify
      fallers. DESIGN: Cross-sectional retrospective. SETTING: Two self-care,
      residential facilities. PARTICIPANTS: a total of 100 healthy old volunteers (mean
      age = 78.4 +/- 5.7). MEASUREMENTS: The study investigated the use of the
      Voluntary Step Execution Test to identify fallers under single and dual-task
      conditions. Berg Balance Test (BBS) and Timed Get Up and Go (TUG) were used to
      assess balance and gait function. RESULTS: There were no significant differences
      found between fallers and non-fallers in BBS and TUG (50.5 +/- 4.6 versus 52.5 +/
      3.4 and 9.4 +/- 3.4 versus 7.98 +/- 2.3 respectively). There were no
      statistically significant differences between non-fallers and fallers across all
      step execution parameters under the single-task condition. However, adding
      cognitive load to the Voluntary Step Execution Test revealed statistically
      significant increases in duration of the preparatory phase, swing time and the
      time to foot-contact (P = 0.035;P = 0.033 and P = 0.037, respectively). Based on
      the coefficients of the logistic regression model participants with dual-task
      step execution times of > or =1,100 ms had five times the risk of falling than
      participants with execution times of <1,100 ms. CONCLUSIONS: The study provides
      evidence that a simple, safe measure of step execution under dual-task conditions
      can identify elderly individuals at risk for falls.

PMID- 17545208
TI  - A novel computer-based technique for the assessment of tremor in Parkinson's
      disease.
AB  - Parkinson's disease (PD) is a common neurodegenerative disease and the diagnosis
      of its idiopathic form remains challenging. The diagnosis of idiopathic form is
      based on clinical features which can have poor sensitivity with about 25% of
      patients diagnosed as having the disease actually having other conditions. In
      this study we assess the suitability and clinical value of a low cost computer
      based system as an aid to diagnosis of PD, in particular the presence of tremor.
      All participants (12 patients and 10 controls) performed a shape-tracing task
      using a graphic tablet attached to a laptop. To assess the presence of tremors in
      the collected data, a statistical spectral analysis of the moment-to-moment
      fluctuations in the position signal of the output from the digitising tablet was
      performed. This allowed the comparison of power spectrums obtained from the
      control and patient responses respectively. A peak in log power between the 5 Hz
      & 6 Hz can clearly be identified in the patient's spectrum and is indicative of
      Parkinson's related tremor and no similar peak could be seen in the control's
      spectrum, suggesting this type of sequential task and automated data analysis may
      be useful in the diagnosis of tremor.

PMID- 17545209
TI  - Antioxidant properties of beta-carboline alkaloids are related to their
      antimutagenic and antigenotoxic activities.
AB  - The beta-carboline alkaloids found in medical plants and in a variety of foods,
      beverages and cigarette smoke have a range of action in various biological
      systems. In vitro studies have demonstrated that these alkaloids can act as
      scavengers of reactive oxygen species. In this paper, we report the in vivo
      antioxidative properties of the aromatic (harmane, harmine, harmol) and dihydro
      beta-carbolines (harmaline and harmalol) studied by using Saccharomyces
      cerevisiae strains proficient and deficient in antioxidant defenses. Their
      antimutagenic activity was also assayed in S. cerevisiae and the antigenotoxicity
      was tested by the comet assay in V79 cell line, when both eukaryotic systems were
      exposed to H(2)O(2). We show that the alkaloids have a significant protective
      effect against H(2)O(2) and paraquat oxidative agents in yeast cells, and that
      their ability to scavenge hydroxyl radicals contributes to their antimutagenic
      and antigenotoxic effects.

PMID- 17545210
TI  - Arsenite slows S phase progression via inhibition of cdc25A dual specificity
      phosphatase gene transcription.
AB  - Arsenic acts as a toxicant, a carcinogen, and an effective chemotherapeutic
      agent, but its mechanisms of action are unclear. We have previously shown that
      treatment of U937 cells with 5 microM sodium arsenite inhibits cell cycle
      progression through each cell cycle phase, including S phase. Cdc25A dual
      specificity phosphatase controls entry into and progression through S phase by
      dephosphorylating sites of inhibitory phosphorylation on cyclin E-cdk2 (Thr14 and
      Tyr15). Immunoblotting reveals that a 3-h treatment of U937 cells with 5 microM
      sodium arsenite results in a dramatic decrease in cdc25A protein levels.
      Coimmunoprecipitation experiments confirm that cyclin E-cdk2 is more
      phosphorylated at Thr14 and Tyr15 in the presence of arsenite, and kinase
      activity assays reveal a decrease in cyclin E-associated cdk2 activity.
      Therefore, arsenite-dependent cdc25A depletion could contribute to S phase
      inhibition. There exists an S phase checkpoint known to be mediated by
      proteasomal cdc25A degradation. However, cycloheximide half-life assay reveals
      that cdc25A is actually stabilized in arsenite-treated cells. Real-time RT-PCR
      shows that cdc25A mRNA levels are substantially decreased with arsenite
      treatment, and actinomycin D half-life assay reveals no change in message
      stability. Decreased cdc25A message translation is shown by sucrose density
      gradient polysomal analysis to be an unlikely cause for the profound arsenite
      dependent reduction in cdc25A protein levels. Studies are ongoing to establish
      the mechanism by which 5 microM arsenite decreases cdc25A message abundance, but
      we surmise that, given the lack of effect on mRNA stability, an inhibition of
      gene transcription is likely involved.

PMID- 17545211
TI  - Toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin in the developing male
      Wistar(Han) rat. II: Chronic dosing causes developmental delay.
AB  - We have investigated whether fetal exposure to 2,3,7,8-tetrachlorodibenzo-p
      dioxin (TCDD) causes defects in the male reproductive system of the rat using
      chronically exposed rats to ensure continuous exposure of the fetus. Five- to six
      week-old rats were exposed to control diet, or diet containing TCDD, to attain an
      average dose of 2.4, 8, and 46 ng TCDD/kg/day for 12 weeks, whereupon the rats
      were mated and allowed to litter; rats were switched to control diet after
      parturition. Male offsprings were allowed to develop until kills on PND70 (25 per
      group) or PND120 (all remaining animals). Offspring from the high-dose group
      showed an increase in total litter loss, and the number of animals alive on
      postnatal day (PND)4 in the high-dose group was approximately 26% less than
      control. The high and medium dose offsprings showed decreased weights at various
      ages. Balano-preputial separation (BPS) was significantly delayed in all three
      dose groups compared to control. There were no significant effects of maternal
      treatment when the offsprings were subjected to a functional observational
      battery or learning tests, with the exception that the high-dose group showed a
      deficit in motor activity. Twenty rats per group were mated to females, and there
      were no significant effects of maternal treatment on the fertility of these rats
      or on the F1 or F2 sex ratio. Sperm parameters at PND70 and 120 showed no
      significant effect of maternal treatment, with the exception that there was an
      increase in the proportion of abnormal sperm in the high-dose group at PND70;
      this is associated with the developmental delay in puberty in this dose group.
      There were no remarkable findings of maternal treatment on organ weights, with
      the exception that testis weights were reduced by approximately 10% at PND70 (but
      not PND120), and although the experiment was sufficiently powered to detect small
      changes, ventral prostate weight was not reduced. There were no significant
      effects of maternal treatment upon histopathological comparison of high-dose and
      control group organs. These data confirm that developmental exposure to TCDD
      shows no potent effect on adult sperm parameters or accessory sexual organs, but
      show that delay in BPS occurs after exposure to low doses of TCDD, and this is
      dependent upon whether TCDD is administered acutely or chronically.

PMID- 17545212
TI  - Toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin in the developing male
      Wistar(Han) rat. I: No decrease in epididymal sperm count after a single acute
      dose.
AB  - It has been reported that fetal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin
      (TCDD) causes defects in the male reproductive system of the rat. We set out to
      replicate and extend these effects using a robust experimental design. Groups of
      75 (control vehicle) or 55 (50, 200, or 1000 ng of TCDD/kg bodyweight) female
      Wistar(Han) rats were exposed to TCDD on gestational day (GD)15, then allowed to
      litter. The high-dose group dams showed no sustained weight loss compared to
      control, but four animals had total litter loss. Pups in the high-dose group
      showed reduced body weight up till day 21, and pups in the medium dose group
      showed reduced body weight in the first week postpartum. Balano-preputial
      separation was significantly delayed in the high-dose group male offspring. There
      were no significant effects of treatment when the offspring were subjected to a
      functional observational battery or mated with females to assess reproductive
      capability. Twenty-five males per group were killed on postnatal day (PND) 70,
      and approximately 60 animals per group (approximately 30 for the high-dose group)
      on PND120 to assess seminology and other end points. At PND120, the two highest
      dose groups showed a statistically significant elevation of sperm counts,
      compared to control; however, this effect was small (approximately 30%), within
      the normal range of sperm counts for this strain of rat, was not reflected in
      testicular spermatid counts nor PND70 data, and is therefore postulated to have
      no biological significance. Although there was an increase in the proportion of
      abnormal sperm at PND70, seminology parameters were otherwise unremarkable.
      Testis weights in the high-dose group were slightly decreased at PND70 and 120,
      and at PND120, brain weights were decreased in the high-dose group, liver to body
      weight ratios were increased for all three dose groups, with an increase in
      inflammatory cell foci in the epididymis in the high-dose group. These data show
      that TCDD is a potent developmental toxin after exposure of the developing fetus
      but that acute developmental exposure to TCDD on GD15 caused no decrease in sperm
      counts.

PMID- 17545213
TI  - Erythrocebus patas monkey offspring exposed perinatally to NRTIs sustain skeletal
      muscle mitochondrial compromise at birth and at 1 year of age.
AB  - Antiretroviral nucleoside reverse transcriptase inhibitors (NRTIs), given to
      human immunodeficiency virus-1-infected pregnant women to prevent vertical viral
      transmission, have caused mitochondrial dysfunction in some human infants. Here,
      we examined mitochondrial integrity in skeletal muscle from offspring of pregnant
      retroviral-free Erythrocebus patas dams administered human-equivalent NRTI doses
      for the last 10 weeks of gestation or for 10 weeks of gestation and 6 weeks after
      birth. Exposures included no drug, Zidovudine (AZT), Lamivudine (3TC), AZT/3TC,
      AZT/Didanosine (ddI), and Stavudine (d4T)/3TC. Offspring were examined at birth
      (n=3 per group) and 1 year (n=4 per group, not including 3TC alone). Circulating
      levels of creatine kinase were elevated at 1 year in the d4T/3TC-exposed group.
      Measurement of oxidative phosphorylation enzyme activities (complexes I, II, and
      IV) revealed minimal NRTI-induced changes at birth and at 1 year. Histochemistry
      for complex IV activity showed abnormal staining with activity depletion at birth
      and 1 year in groups exposed to AZT alone and to the 2-NRTI combinations.
      Electron microscopy of skeletal muscle at birth and 1 year of age showed mild to
      severe mitochondrial damage in all the NRTI-exposed groups, with 3TC inducing
      mild damage and the 2-NRTI combinations inducing extensive damage. At birth,
      mitochondrial DNA (mtDNA) was depleted by approximately 50% in groups exposed to
      AZT alone and the 2-NRTI combinations. At 1 year, the mtDNA levels had increased
      but remained significantly below normal. Therefore, skeletal muscle mitochondrial
      compromise occurs at birth and persists at 1 year of age (46 weeks after the last
      NRTI exposure) in perinatally exposed young monkeys, suggesting that similar
      events may occur in NRTI-exposed human infants.

PMID- 17545214
TI  - Atrial fibrillation reduces the atrial impedance amplitude during cardiac cycle:
      a novel detection algorithm to improve recognition of atrial fibrillation in
      pacemaker patients.
AB  - AIMS: In carriers of dual chamber pacemakers and implantable cardioverter
      defibrillators (ICD), detection of atrial fibrillation (AF) is crucial for
      adequate mode switch function and to avoid inappropriate shock delivery.
      Detection algorithms rely on the atrial rate and on the relationship of atrial to
      ventricular intracardiac electrograms, but the relative portion of misclassified
      AF episodes remains high. Although myocardial impedance is a reliable indicator
      of contraction, little is known about atrial impedance as a marker of atrial
      arrhythmias. Methods During an electrophysiological study, we investigated the
      effect of induced AF on impedance at the right atrial free wall (RAFW) and right
      atrial appendage (RAA) in 20 patients. Using biphasic square-wave pulses (128 Hz,
      200 microA/15 micros), impedance changes were recorded during sinus rhythm (SR
      1), atrial pacing at 120 beats/min, AF induced by rapid atrial burst pacing, and
      after spontaneous AF termination (SR-2). Results At the RAA, peak-to-peak
      impedance amplitude during cardiac cycle (DeltaZ) dropped from 51.7 +/- 35.3
      Omega (SR-1) or 49.6 +/- 30.6 Omega (pacing) to 24.6 +/- 22.0 Omega (AF, P< or
      =0.0005), and subsequently increased to 37.7 +/- 24.7 Omega (SR-2, P < or =
      0.0004 v. AF). At the RAFW, DeltaZ changed from 16.2 +/- 15.5 Omega (SR-1) or
      13.5 +/- 9.9 Omega (pacing) to 5.9 +/- 4.1 Omega (AF, P < or = 0.003), and to
      11.4 +/- 10.7 Omega (SR-2, P < or = 0.015). Given a discrimination threshold of
      65%, the sensitivity and the specificity of DeltaZ to detect AF were 79 +/- 18
      and 89 +/- 14%, respectively (95% confidence interval). CONCLUSION: AF causes
      DeltaZ drop in pacemaker and ICD recipients. This impedance based algorithm can
      be used as an alternative method of AF detection.

PMID- 17545215
TI  - Effect of hypoxia on fatigue development in rat muscle composed of different
      fibre types.
AB  - This study investigated the relationship between hypoxia and the rate of fatigue
      development in contracting rat hindlimb muscles composed primarily of different
      fibre types. Hindlimb muscles of 11 rats were exposed, and the soleus (SOL) and
      gastrocnemius/plantaris (GP) were each isolated with circulation intact and
      attached to individual force transducers. Rats were then equilibrated with either
      normoxic (N; arterial partial pressure of O(2) 87.7 +/- 1.5 mmHg) or hypoxic
      conditions (H; arterial partial pressure of O(2) 30.0 +/- 2.4 mmHg) using an
      inspired O(2) fraction of 0.21 and 0.10, respectively. The stimulation protocol
      consisted of 2 min each at 0.125, 0.25, 0.33 and 0.5 tetanic contractions s(-1)
      sequentially for both conditions. Following the 8 min stimulation period,
      relative developed muscle tension (% of maximal) was nearly identical for both H
      and N in SOL (54.2 +/- 3.5 versus 54.3 +/- 4.2%), but was significantly (P <
      0.05) lower in H than N (10.8 +/- 0.9 versus 43.0 +/- 8.9%) in GP, indicating a
      greater amount of fatigue during hypoxia only in the GP. Soleus phosphocreatine
      (PCr) content fell to similar levels (24.1 +/- 1.6 versus 21.1 +/- 4.9 mmol (kg
      dry weight (dw))(-1)) during both H and N, but in the white portion of the
      gastrocnemius (WG), PCr was significantly lower following H than N (14.3 +/- 1.5
      versus 34.0 +/- 6.0 mmol (kg dw)(-1)). Similarly, muscle lactate increased in
      both fibre types at fatigue, but only in WG was the increase significantly
      greater with H (SOL 7.1 +/- 2.0 versus 5.3 +/- 1.1 mmol (kg dw)(-1); WG 13.7 +/-
      4.5 versus 5.3 +/- 2.2 mmol (kg dw)(-1)). Increases in calculated muscle [H(+)],
      free ADP and free AMP were similar between N and H in SOL but were significantly
      greater during H compared with N in WG. These data demonstrate that hypoxia
      induces greater fatigue and disruption of cellular homeostasis in rat hindlimb
      muscle composed primarily of fibres with low oxidative capacity compared with
      those of a more oxidative type.

PMID- 17545216
TI  - Role of vascular bed compliance in vasomotor control in human skeletal muscle.
AB  - The current view of neurogenic vasomotor control in skeletal muscle is based
      largely on changes in vascular bed resistance. The purpose of this study was to
      determine to what extent vascular bed compliance may also play a role in this
      regulation. For this purpose, pressure waveforms (Millar and Finometer) and flow
      waveforms (Doppler ultrasound) were measured simultaneously in the brachial
      artery of seven healthy individuals during physiological manoeuvres which were
      expected to produce non-neurogenic changes in resistance (wrist-cuff occlusion; n
      = 5) or compliance (arm elevation; n = 6) of the forearm vascular bed. Vascular
      resistance (R) was calculated from the average flow and pressure values. A lumped
      Windkessel model was used to obtain vascular bed compliance (C) from these
      concurrently measured waveforms. Compared with baseline (3.81 +/- 1.59 ml min(-1)
      mmHg(-1)), wrist occlusion increased R (65 +/- 75%; P < 0.05) with minimal change
      in C (-15 +/- 16%; n.s.). Compared with the arm in neutral position (0.0075 +/-
      0.003 ml mmHg(-1)), elevation of the arm above heart level produced a 86 +/- 41%
      increase in C (P < 0.05) with little change in R (-5 +/- 11%). In addition,
      neurogenic changes were assessed during lower body negative pressure (LBNP) and a
      cold pressor test (CPT; n = 7). Lower body negative pressure induced a 29 +/- 24%
      increase in R and a 26 +/- 12% decrease in C (both P < 0.05). The CPT induced no
      consistent change in R but a 22 +/- 7% reduction in C (P < 0.05). It was
      concluded that vascular bed compliance is an independent variable which should be
      considered along with vascular bed resistance in the mechanics of vasomotor
      regulation in skeletal muscle.

PMID- 17545217
TI  - Emergence of Vibrio cholerae O1 Inaba in Andaman & Nicobar Islands, India.

PMID- 17545218
TI  - Hodgkin's reed-sternberg cell line (KM-H2) promotes a bidirectional
      differentiation of CD4+CD25+Foxp3+ T cells and CD4+ cytotoxic T lymphocytes from
      CD4+ naive T cells.
AB  - A recent report revealed that a large population of Hodgkin's lymphoma
      infiltrating lymphocytes (HLILs) consisted of regulatory T cells. In this study,
      we cocultured CD4+ naive T cells with KM-H2, which was established as a Hodgkin's
      Reed-Sternberg cell line, to clarify their ability to induce CD25+ Forkhead box
      P3+ (Foxp3+) T cells. The characteristic analyses of T cells cocultured with KM
      H2 revealed the presence of CD4+CD25+ T cells. They expressed CTLA-4,
      glucocorticoid-induced TNFR family-related gene, and Foxp3 and could produce
      large amounts of IL-10. Conversely, KM-H2 also generated CD4+ CTLs, which
      expressed Granzyme B and T cell intracellular antigen-1 in addition to Foxp3+ T
      cells. They exhibit a strong cytotoxic effect against the parental KM-H2. In
      conclusion, KM-H2 promotes a bidirectional differentiation of CD4+ naive T cells
      toward Foxp3+ T cells and CD4+ CTLs. In addition to KM-H2, several cell lines
      that exhibit the APC function were able to generate Foxp3+ T cells and CD4+ CTLs.
      Conversely, the APC nonfunctioning cell lines examined did not induce both types
      of cells. Our findings suggest that the APC function of tumor cells is essential
      for the differentiation of CD4+ naive T cells into CD25+Foxp3+ T cells and CD4+
      CTLs and at least partly explains the predominance of CD25+Foxp3+ T cells in
      HLILs and their contribution to a better prognosis. Therefore, in APC-functioning
      tumors, including classical Hodgkin lymphomas, which generate Foxp3+ T cells and
      CD4+ CTLs, these T cell repertories play a beneficial role synergistically in
      disease stability.

PMID- 17545219
TI  - Protein dynamics and proteolysis in plant vacuoles.
AB  - Plant cells cannot live without their vacuoles. The tissues and organs of a plant
      contain a wide variety of differentiated and specialized vacuoles -- even a
      single plant cell can possess two or more types of vacuoles. Vacuolar proteins
      are encoded by nuclear genes and synthesized in the cytoplasm. Their transport
      into the vacuolar compartment is under cytoplasmic control. Transcription seems
      to be a major control level for differential protein supply to the vacuoles. It
      is at this level that vacuole differentiation and functions are mainly integrated
      into cellular processes. Recycling amino acids generated by protein degradation
      is a major function of the vacuole. This is most evident when storage proteins
      are mobilized in storage tissues of generative or vegetative organs in order to
      nourish the embryo of germinating seeds or sprouting buds. When specific proteins
      are transferred to the vacuole for immediate degradation this compartment
      contributes to the adaptation of protein complexes in response to changes in
      developmental or environmental conditions. Vacuolar proteases are involved in
      protein degradation during reversible senescence and programmed cell death, which
      is also called irreversible senescence. Vacuoles contribute to defence against
      pathogens and herbivores by limited and unlimited proteolysis. Our present
      knowledge on functions and processes of vacuolar protein dynamics in plants is
      reviewed. Research perspectives are deduced.

PMID- 17545220
TI  - Transcriptional responses of Arabidopsis thaliana ecotypes with different
      glucosinolate profiles after attack by polyphagous Myzus persicae and
      oligophagous Brevicoryne brassicae.
AB  - Plants are equipped with a range of defence mechanisms against herbivorous
      insects. In cruciferous species, jasmonic acid, salicylic acid, and ethylene
      along with glucosinolates and their hydrolysis products play important roles in
      plant protection and plant-insect communication. In turn, a number of herbivores
      have adapted to plants that contain glucosinolates. As a result of adaptation to
      their host plants, specialized insects may elicit different plant-inducible
      responses than generalists. Oligonucleotide microarrays and qRT-PCR analysis were
      used to characterize transcriptional profiles of Arabidopsis thaliana plants in
      response to infestation with a generalist aphid, Myzus persicae, or a cruciferous
      plant specialist, Brevicoryne brassicae. To find possible differences and
      similarities in molecular responses between plants differing in predominant
      glucosinolate hydrolysis products, three ecotypes of A. thaliana were chosen:
      Wassilewskija (Ws), Cape Verde Islands (Cvi), and Landsberg erecta (Ler), which,
      respectively, produce mainly isothiocyanates, epithionitriles, and nitriles. In
      all three ecotypes, general stress-responsive genes, genes belonging to
      octadecanoid and indole glucosinolate synthesis pathways were induced upon both
      generalist and specialist attack. By contrast, transcription of myrosinases,
      enzymes hydrolysing glucosinolates, was suppressed. The induction of the jasmonic
      acid synthesis pathway was strongest in Cvi, while the up-regulation of the
      indole glucosinolate synthesis pathway was highest in Ler, suggesting a slightly
      different defence strategy in these two ecotypes. Specialist and generalist
      infestations caused statistically significant differential regulation of 60 genes
      in Ws and 21 in Cvi. Among these were jasmonic acid and tryptophan synthesis
      pathway enzymes, and pathogenesis related protein (PR1). Insect no-choice
      experiments revealed lowered fitness of B. brassicae on Ler and Cvi in comparison
      to Ws, but no ecotype-dependent change in fecundity of M. persicae. Targeted
      studies employing constructs of GUS reporter gene under the control of promoters
      from CYP79B2 and CYP79B3 genes showed insect-specific induction of the indole
      glucosinolates synthesis pathway.

PMID- 17545221
TI  - Microtubule dynamics in relation to osmotic stress-induced ABA accumulation in
      Zea mays roots.
AB  - Microtubules play important roles in many physiological processes such as plant
      responses to drought stress. Abscisic acid (ABA) accumulates significantly in
      plants in response to drought conditions, which has been considered as a major
      response for plants to enhance drought tolerance. In this work, the focus was on
      the possible roles of microtubules in the induction of ABA biosynthesis in the
      roots of Zea mays when subjected to osmotic stress. The dynamic changes of
      microtubules in response to the stress were investigated by immunofluorescence
      staining, enzyme-linked immunosorbent assay, and a pharmacological approach.
      Disruption and stabilization of microtubules both significantly stimulated ABA
      accumulation in maize root cells, although this stimulation was markedly lower
      than that caused by osmotic stress. Cells in which the microtubule stability had
      been changed did not respond further to osmotic stress in terms of ABA
      biosynthesis. However, treatment with both a microtubule de-stabilizer and a
      stabilizer enhanced the sensitivity of cells to osmotic stress in terms of ABA
      accumulation. It is suggested that both osmotic stress and changes in microtubule
      dynamics would trigger maize root cells to biosynthesize ABA, and interactions
      between osmotic stress and microtubule dynamics would have an effect on ABA
      accumulation in root cells, although the exact mechanism is not clear at present.

PMID- 17545222
TI  - Modulation of flower colour by rationally designed dominant-negative chalcone
      synthase.
AB  - The intensity of flower colour, mainly determined by the amount of anthocyanin,
      is an important horticultural trait. To modulate flower colour intensity, post
      transcriptional gene silencing (PTGS)-based technology has been widely used. The
      constraint of PTGS, however, is that it requires a high degree of conservation in
      the nucleotide sequences of the target and the silencer. Further, it is difficult
      to restrict PTGS to the desired tissue or organ due to its systemic spread. To
      overcome these problems, dominant-negative chalcone synthase (CHS) enzymes have
      been developed by mutating a cysteine that is essential for the catalytic
      activity and a methionine that protrudes into the adjoining CHS monomer, as shown
      through crystallography. The dominant-negative action of mutated CHS enzymes from
      Mazus japonicus are demonstrated using transgenic Arabidopsis. Also, the
      modulation of Petunia flower colour intensity by the dominant-negative CHS is
      shown. The data support the crystallography result showing the importance of the
      protruding methionine for the function of the adjoining CHS monomer. Furthermore,
      the modulation of anthocyanin production by the mutated Mazus CHS in Arabidopsis
      and petunia suggests that the dominant-negative CHS can be used even in distantly
      related species.

PMID- 17545223
TI  - Characterization of monofunctional aspartate kinase genes in maize and their
      relationship with free amino acid content in the endosperm.
AB  - A quantitative trait locus has previously been identified in maize (Zea mays L.)
      that influences the level of free amino acids in the endosperm, especially those
      from the aspartate pathway: lysine, threonine, methionine, leucine, and
      isoleucine. Because this locus occurs in a region of the genome containing ask2,
      a monofunctional aspartate kinase, the nature of the monofunctional aspartate
      kinase genes in the parental inbreds, Oh545o2 and Oh51Ao2, was investigated. Two
      genes, Ask1 and Ask2 were isolated, and Ask2 was mapped to the ask2 locus.
      Nucleotide sequence analysis of the Ask2 alleles from Oh545o2 and Oh51Ao2 showed
      they differ by one amino acid. Both alleles complemented a yeast aspartate kinase
      mutant, hom3, and based on the growth of the yeast mutant it appeared that Ask2
      Oh545o2 produces an enzyme with greater total activity than that encoded by the
      Oh51Ao2 allele. The results suggest that the higher level of free amino acids
      derived from the aspartate pathway in Oh545o2 endosperm results from a single
      amino acid change in the ASK2 enzyme that has pleiotropic effects on its
      activity.

PMID- 17545224
TI  - Insights into rubber biosynthesis from transcriptome analysis of Hevea
      brasiliensis latex.
AB  - Hevea brasiliensis is the most widely cultivated species for commercial
      production of natural rubber (cis-polyisoprene). In this study, 10,040 expressed
      sequence tags (ESTs) were generated from the latex of the rubber tree, which
      represents the cytoplasmic content of a single cell type, in order to analyse the
      latex transcription profile with emphasis on rubber biosynthesis-related genes. A
      total of 3,441 unique transcripts (UTs) were obtained after quality editing and
      assembly of EST sequences. Functional classification of UTs according to the Gene
      Ontology convention showed that 73.8% were related to genes of unknown function.
      Among highly expressed ESTs, a significant proportion encoded proteins related to
      rubber biosynthesis and stress or defence responses. Sequences encoding rubber
      particle membrane proteins (RPMPs) belonging to three protein families accounted
      for 12% of the ESTs. Characterization of these ESTs revealed nine RPMP variants
      (7.9-27 kDa) including the 14 kDa REF (rubber elongation factor) and 22 kDa SRPP
      (small rubber particle protein). The expression of multiple RPMP isoforms in
      latex was shown using antibodies against REF and SRPP. Both EST and quantitative
      reverse transcription-PCR (QRT-PCR) analyses demonstrated REF and SRPP to be the
      most abundant transcripts in latex. Besides rubber biosynthesis, comparative
      sequence analysis showed that the RPMPs are highly similar to sequences in the
      plant kingdom having stress-related functions. Implications of the RPMP function
      in cis-polyisoprene biosynthesis in the context of transcript abundance and
      differential gene expression are discussed.

PMID- 17545225
TI  - Functional cross-talk between two-component and phytochrome B signal transduction
      in Arabidopsis.
AB  - The A-type response regulator ARR4 is an element in the two-component signalling
      network of Arabidopsis. ARR4 interacts with the N-terminus of the red/far-red
      light photoreceptor phytochrome B (phyB) and functions as a modulator of
      photomorphogenesis. In concert with other A-type response regulators, ARR4 also
      participates in the modulation of the cytokinin response pathway. Here evidence
      is presented that ARR4 directly modulates the activity state of phyB in planta,
      not only under inductive but also under extended irradiation with red light.
      Mutation of the phosphorylatable aspartate to asparagine within the receiver
      domain creates a version of ARR4 that negatively affects photomorphogenesis.
      Additional evidence suggests that ARR4 activity is regulated by a phosphorelay
      mechanism that depends on the AHK family of cytokinin receptors. Accordingly, the
      ability of ARR4 to function on phyB is modified by exogenous application of
      cytokinin. These results implicate a cross-talk between cytokinin and light
      signalling mediated by ARR4. This cross-talk enables the plant to adjust light
      reponsiveness to endogenous requirements in growth and development.

PMID- 17545226
TI  - Evaluation of drought response of two poplar clones (Populus x canadensis Monch
      'I-214' and P. deltoides Marsh. 'Dvina') through high resolution analysis of stem
      growth.
AB  - Different irrigation effects on stem radius variation (DeltaR) and maximum daily
      shrinkage (MDS) in Populus deltoides 'Dvina' and Populusxcanadensis 'I-214' were
      studied to assess differences in drought tolerance between clones. One-year-old
      trees growing in concrete tanks were submitted to two irrigation regimes (natural
      rainfall and irrigation) from 24 June to 10 August, and DeltaR was monitored by
      automatic point dendrometers. Independently of the irrigation regime, 'Dvina'
      showed a higher stem radial increment than 'I-214'. In both clones, the first
      response to changed soil water content was a significant increase in MDS, whilst
      DeltaR decreased about 20 d later when pre-dawn leaf water potential (Psipd)
      dropped below -0.4 MPa. However, they displayed different strategies to overcome
      drought. 'Dvina' maintained a positive DeltaR for longer than 'I-214', which had
      lower leaf Psipd and greater leaf abscission at the end of the drought period.
      After irrigation resumed, 'Dvina' showed a higher capacity to restore stem
      growth. 'I-214' was probably unable to recover secondary growth because of higher
      leaf abscission during drought stress and the production of newly expanded leaves
      during recovery. It is concluded that the larger radial growth of 'Dvina' derived
      from a better water use (carbon uptake versus water loss) than 'I-214' under
      limited water availability.

PMID- 17545227
TI  - Ion-mediated enhancement of xylem hydraulic conductivity is not always suppressed
      by the presence of Ca2+ in the sap.
AB  - The physiological significance of ion-mediated enhancement of xylem hydraulic
      conductivity (K(h)) in planta has recently been questioned. The phenomenon has
      been suggested to be an artefact caused by the use of deionized water as a
      reference fluid during measurements of the impact of different ions on K(h). In
      the present study, ion-mediated changes in K(h) were measured in twigs of five
      woody species during perfusion with 25 mM KCl compared with different reference
      fluids like deionized water, a commercial mineral water containing different ions
      (including 0.5 mM Ca(2+)), and a 1 mM CaCl(2) solution. Both fully hydrated twigs
      and twigs with about 50% loss of hydraulic conductivity due to cavitation-induced
      embolism were tested. Adding 25 mM KCl to the three reference fluids caused K(h)
      to increase by about 20%. The KCl-mediated increase of K(h) was even larger (up
      to 100%) in embolized twigs. The presence of Ca(2+) in the reference solution
      decreased, but not suppressed, the KCl-mediated enhancement of K(h) in fully
      hydrated twigs of three species, but not in the other two species tested. Ca(2+)
      did not affect the K(h) response to KCl in embolized twigs. These data suggest
      that the recently reported suppression of the 'ionic effect' by the presence of
      calcium in the xylem sap is not a general phenomenon and that ion-mediated
      changes of K(h) may play a role in planta partially to compensate for cavitation
      induced loss of xylem hydraulic conductivity.

PMID- 17545228
TI  - Functional characterization of LePT4: a phosphate transporter in tomato with
      mycorrhiza-enhanced expression.
AB  - Many plant roots acquire inorganic phosphate (Pi) from soils directly through the
      root-soil interface via high-affinity Pi transporters and/or through symbiotic
      associations between the cortical cells and arbuscular mycorrhizal fungi. In
      tomato, three phosphate transporters (LePT3, LePT4, and LePT5) are up-regulated
      upon colonization by arbuscular mycorrhizal fungi. In this study, the role of
      LePT4 in tomato is elucidated by molecular and physiological characterizations of
      a loss-of-function mutant lept4. In the absence of mycorrhizal infection and
      under solution-Pi concentrations (Cp) of 0.05 mM and 0.5 mM, the mutant exhibited
      severe Pi-deficiency symptoms which were associated with significantly lower Pi
      uptake as compared with that of the wild type. However, at a Cp of 5 mM, lept4
      grew better than the wild type. Mycorrhizal infection at a Cp of 0.05 mM resulted
      in a significant increase in the transcripts of LePT4 in the wild type and a
      concomitant 2-fold increase in Pi uptake. Although upon mycorrhizal infection,
      lept4 also exhibited an increased Pi uptake, it was significantly lower than that
      of the wild type. Under a Cp of 1 mM and in the absence of mycorrhizal infection,
      LePT4 expression was suppressed in the wild type and a mutation in this gene
      resulted in a slight reduction in total Pi uptake. These data highlight the
      pivotal role of LePT4 in mycorrhizal-mediated Pi uptake in tomato, and show that
      this function may not be fully compensated by other members of the family.
      Characterization of the mycorrhiza-associated Pi transporter lept4 mutant, along
      with expression analysis of LePT3, provides evidence for the different routes of
      mycorrhiza-mediated Pi uptake in plants.

PMID- 17545229
TI  - Peroxisomal membrane manganese superoxide dismutase: characterization of the
      isozyme from watermelon (Citrullus lanatus Schrad.) cotyledons.
AB  - In this work the manganese superoxide dismutase (Mn-SOD) bound to peroxisomal
      membranes of watermelon cotyledons (Citrullus lanatus Schrad.) was purified to
      homogeneity and some of its molecular properties were determined. The stepwise
      purification procedure consisted of ammonium sulphate fractionation, batch anion
      exchange chromatography, and anion-exchange and gel-filtration column
      chromatography using a fast protein liquid chromatography system. Peroxisomal
      membrane Mn-SOD (perMn-SOD; EC 1.15.1.1) was purified 5600-fold with a yield of
      2.6 mug of enzyme g(-1) of cotyledons, and had a specific activity of 480 U mg(
      1) of protein. The native molecular mass determined for perMn-SOD was 108 000 Da,
      and it was composed of four equal subunits of 27 kDa, which indicates that perMn
      SOD is a homotetramer. Ultraviolet and visible absorption spectra of the enzyme
      showed a shoulder at 275 nm and two absorption maxima at 448 nm and 555 nm,
      respectively. By isoelectric focusing, a pI of 5.75 was determined for perMn-SOD.
      In immunoblot assays, purified perMn-SOD was recognized by a polyclonal antibody
      against Mn-SOD from pea leaves, and the peroxisomal enzyme rapidly dissociated in
      the presence of dithiothreitol and SDS. The potential binding of the Mn-SOD
      isozyme to the peroxisomal membrane was confirmed by immunoelectron microscopy
      analysis. The properties of perMn-SOD and the mitMn-SOD are compared and the
      possible function in peroxisomal membranes of the peripheral protein Mn-SOD is
      discussed.

PMID- 17545230
TI  - Competitive markets for European public health research?

PMID- 17545231
TI  - Racism in health and health care in Europe: reality or mirage?

PMID- 17545232
TI  - Racism in health and health care in Europe: where does the Netherlands stand?

PMID- 17545233
TI  - Interaction of a self-assembling peptide with oligonucleotides: complexation and
      aggregation.
AB  - Molecular interaction of a self-assembling peptide, EAK16-II, to single- and
      double-stranded oligodeoxynucleotides (ODNs) was investigated under various
      solution conditions. The molecular events leading to EAK-ODN complexation and
      further aggregation were elucidated using a series of spectroscopic and
      microscopic methods. Despite the ability to self-assemble, EAK molecules bind to
      ODN molecules first upon mixing, resulting in EAK-ODN complexes. The complexes
      further associate to form EAK-ODN aggregates. A method based on UV-Vis absorption
      and centrifugation was developed to quantify the fraction of ODNs in the
      aggregates. The results were used to construct binding isotherms via a binding
      density function analysis. To compare the effects of different pH values and
      nucleotide types, the modified noncooperative McGhee and von Hippel model was
      used to extract binding parameters from the binding isotherms. The binding
      constant of EAK to ODNs was higher at pH 4 than at pH 7, and no binding was
      observed at pH 11, indicating that the interaction involved is primarily
      electrostatic in nature. EAK bound more strongly to single-stranded ODNs. The EAK
      ODN aggregates were further visualized using atomic force microscopy; their size
      distribution as a function of EAK concentration was monitored by dynamic light
      scattering. The timescale for the EAK-ODN aggregation was on the order of minutes
      by fluorescence anisotropy and steady-state light scattering experiments.
      Fluorescence quenching experiments demonstrated that the ODNs in the aggregates
      were less accessible to the solvent, demonstrating a potential of oligonucleotide
      encapsulation by the self-assembling peptide.

PMID- 17545234
TI  - Measurement and modeling of Ca2+ waves in isolated rabbit ventricular
      cardiomyocytes.
AB  - The time course and magnitude of the Ca(2+) fluxes underlying spontaneous Ca(2+)
      waves in single permeabilized ventricular cardiomyocytes were derived from
      confocal Fluo-5F fluorescence signals. Peak flux rates via the sarcoplasmic
      reticulum (SR) release channel (RyR2) and the SR Ca(2+) ATPase (SERCA) were not
      constant across a range of cellular [Ca(2+)] values. The Ca(2+) affinity (K(mf))
      and maximum turnover rate (V(max)) of SERCA and the peak permeability of the RyR2
      mediated Ca(2+) release pathway increased at higher cellular [Ca(2+)] loads. This
      information was used to create a computational model of the Ca(2+) wave, which
      predicted the time course and frequency dependence of Ca(2+) waves over a range
      of cellular Ca(2+) loads. Incubation of cardiomyocytes with the Ca(2+) calmodulin
      (CaM) kinase inhibitor autocamtide-2-related inhibitory peptide (300 nM, 30 mins)
      significantly reduced the frequency of the Ca(2+) waves at high Ca(2+) loads.
      Analysis of the Ca(2+) fluxes suggests that inhibition of CaM kinase prevented
      the increases in SERCA V(max) and peak RyR2 release flux observed at high
      cellular [Ca(2+)]. These data support the view that modification of activity of
      SERCA and RyR2 via a CaM kinase sensitive process occurs at higher cellular
      Ca(2+) loads to increase the maximum frequency of spontaneous Ca(2+) waves.

PMID- 17545235
TI  - Interaction of the C-terminal region of the Ggamma protein with model membranes.
AB  - Heterotrimeric G-proteins interact with membranes. They accumulate around
      membrane receptors and propagate messages to effectors localized in different
      cellular compartments. G-protein-lipid interactions regulate G-protein cellular
      localization and activity. Although we recently found that the Gbetagamma dimer
      drives the interaction of G-proteins with nonlamellar-prone membranes, little is
      known about the molecular basis of this interaction. Here, we investigated the
      interaction of the C-terminus of the Ggamma(2) protein (P(gamma)-FN) with model
      membranes and those of its peptide (P(gamma)) and farnesyl (FN) moieties alone. X
      ray diffraction and differential scanning calorimetry demonstrated that P(gamma)
      FN, segregated into P(gamma)-FN-poor and -rich domains in
      phosphatidylethanolamine (PE) and phosphatidylserine (PS) membranes. In PE
      membranes, FN increased the nonlamellar phase propensity. Fourier transform
      infrared spectroscopy experiments showed that P(gamma) and P(gamma)-FN interact
      with the polar and interfacial regions of PE and PS bilayers. The binding of
      P(gamma)-FN to model membranes is due to the FN group and positively charged
      amino acids near this lipid. On the other hand, membrane lipids partially altered
      P(gamma)-FN structure, in turn increasing the fluidity of PS membranes. These
      data highlight the relevance of the interaction of the C-terminal region of the
      Ggamma protein with the cell membrane and its effect on membrane structure.

PMID- 17545236
TI  - An infrared spectroscopic study of the conformational transition of elastin-like
      polypeptides.
AB  - The infrared spectroscopy of elastin-like polypeptides and the relation to the
      inverse thermal transition are discussed. To correlate the spectroscopic
      observations with structure a density function theory model was created that
      captures the essential hydrogen bonding and packing of the beta-spiral structure
      proposed for elastin and elastin-like polypeptides. The infrared spectrum was
      calculated using periodic boundary conditions and a method for estimating the
      difference dipole moment permits both frequencies and intensities to be obtained
      for the modeling of spectra. The two observed amide I bands at 1615 cm(-1) and
      1656 cm(-1) are shown to arise from the beta-spiral structure. The increase in
      intensity of these bands with increasing salt concentration and temperature is
      assigned to the closer association of strands of the beta-spiral. The sharp
      inverse temperature transition is observed within 1 degrees C and involves a
      change in secondary structure that involves formation of interstrand beta-sheets
      for approximately 25% of the amino acids. This conclusion is consistent with
      available data and simulations that have been reported to date.

PMID- 17545237
TI  - Molecular dynamics simulations reveal a disorder-to-order transition on
      phosphorylation of smooth muscle myosin.
AB  - We have performed molecular dynamics simulations of the phosphorylated (at S-19)
      and the unphosphorylated 25-residue N-terminal phosphorylation domain of the
      regulatory light chain (RLC) of smooth muscle myosin to provide insight into the
      structural basis of regulation. This domain does not appear in any crystal
      structure, so these simulations were combined with site-directed spin labeling to
      define its structure and dynamics. Simulations were carried out in explicit water
      at 310 K, starting with an ideal alpha-helix. In the absence of phosphorylation,
      large portions of the domain (residues S-2 to K-11 and R-16 through Y-21) were
      metastable throughout the simulation, undergoing rapid transitions among alpha
      helix, pi-helix, and turn, whereas residues K-12 to Q-15 remained highly
      disordered, displaying a turn motif from 1 to 22.5 ns and a random coil pattern
      from 22.5 to 50 ns. Phosphorylation increased alpha-helical order dramatically in
      residues K-11 to A-17 but caused relatively little change in the immediate
      vicinity of the phosphorylation site (S-19). Phosphorylation also increased the
      overall dynamic stability, as evidenced by smaller temporal fluctuations in the
      root mean-square deviation. These results on the isolated phosphorylation domain,
      predicting a disorder-to-order transition induced by phosphorylation, are
      remarkably consistent with published experimental data involving site-directed
      spin labeling of the intact RLC bound to the two-headed heavy meromyosin. The
      simulations provide new insight into structural details not revealed by
      experiment, allowing us to propose a refined model for the mechanism by which
      phosphorylation affects the N-terminal domain of the RLC of smooth muscle myosin.

PMID- 17545238
TI  - Structural characterization of ferric hemoglobins from three antarctic fish
      species of the suborder notothenioidei.
AB  - Spontaneous autoxidation of tetrameric Hbs leads to the formation of Fe (III)
      forms, whose physiological role is not fully understood. Here we report
      structural characterization by EPR of the oxidized states of tetrameric Hbs
      isolated from the Antarctic fish species Trematomus bernacchii, Trematomus
      newnesi, and Gymnodraco acuticeps, as well as the x-ray crystal structure of
      oxidized Trematomus bernacchii Hb, redetermined at high resolution. The oxidation
      of these Hbs leads to formation of states that were not usually detected in
      previous analyses of tetrameric Hbs. In addition to the commonly found aquo-met
      and hydroxy-met species, EPR analyses show that two distinct hemichromes coexist
      at physiological pH, referred to as hemichromes I and II, respectively. Together
      with the high-resolution crystal structure (1.5 A) of T. bernacchii and a survey
      of data available for other heme proteins, hemichrome I was assigned by x-ray
      crystallography and by EPR as a bis-His complex with a distorted geometry,
      whereas hemichrome II is a less constrained (cytochrome b5-like) bis-His complex.
      In four of the five Antartic fish Hbs examined, hemichrome I is the major form.
      EPR shows that for HbCTn, the amount of hemichrome I is substantially reduced. In
      addition, the concomitant presence of a penta-coordinated high-spin Fe (III)
      species, to our knowledge never reported before for a wild-type tetrameric Hb,
      was detected. A molecular modeling investigation demonstrates that the presence
      of the bulkier Ile in position 67beta in HbCTn in place of Val as in the other
      four Hbs impairs the formation of hemichrome I, thus favoring the formation of
      the ferric penta-coordinated species. Altogether the data show that ferric states
      commonly associated with monomeric and dimeric Hbs are also found in tetrameric
      Hbs.

PMID- 17545239
TI  - Relationship between membrane physical properties and secretory phospholipase A2
      hydrolysis kinetics in S49 cells during ionophore-induced apoptosis.
AB  - During apoptosis, changes occur in lymphocyte membranes that render them
      susceptible to hydrolysis by secretory phospholipase A(2) (sPLA(2)). To study the
      relevant mechanisms, a simplified model of apoptosis using a calcium ionophore
      was applied. Kinetic and flow cytometry experiments provided key observations
      regarding ionophore treatment: the initial rate of hydrolysis was elevated at all
      enzyme concentrations, the total amount of reaction product was increased
      fourfold, and adsorption of the enzyme to the membrane surface was unaltered.
      Analysis of these results suggested that susceptibility during calcium-induced
      apoptosis is limited by availability of substrate rather than adsorption of
      enzyme. Fluorescence experiments identified three membrane alterations during
      apoptosis that might affect substrate access to the sPLA(2) active site. First,
      intercalation of merocyanine 540 into the membrane was improved, suggesting an
      increase in lipid spacing. Second, laurdan detected increased solvation of the
      lower headgroup region of the membrane. Third, the rate at which fluorescent
      lipids could be removed from the membrane by albumin was enhanced, implying
      greater vertical mobility of phospholipids. Thus, it is proposed that the
      membranes of apoptotic cells become susceptible to sPLA(2) through a reduction in
      lipid-neighbor interactions that facilitates migration of phospholipids into the
      enzyme active site.

PMID- 17545241
TI  - Tank-tread frequency of the red cell membrane: dependence on the viscosity of the
      suspending medium.
AB  - Single human red cells were suspended in media with viscosities ranging from 12.9
      to 109 mPa s and subjected to shear flow ranging from 1/s to 290/s in a
      rheoscope. This is a transparent cone-plate chamber adapted to a microscope. The
      motion of the membrane around red cells oriented in a steady-state fashion in the
      shear field (tank-tread motion) was videotaped. The projected length and width of
      the cells as well as the frequency of tank-tread motion were measured. One
      thousand eight-hundred seventy-three cells of three blood donors were evaluated.
      The frequency increased with the mean shear rate in an almost linear fashion. The
      slope of this dependence increased weakly with the viscosity of the suspending
      medium. No correlation was found between the frequency and four morphological red
      cell parameters: the projected length and width of the cells as well as the ratio
      and the square root of the product of these quantities. The energy dissipation
      within the red cell membrane was estimated based on the measured parameters and
      compared to the energy dissipation in the undisturbed shear flow. At constant
      mean shear rate the rise of the energy dissipation with viscosity is slower
      whereas at constant viscosity the rise with the shear rate is steeper than in the
      undisturbed shear flow. A fit of the data collected in this work to a theoretical
      red cell model might allow one to determine intrinsic mechanical constants in the
      low deformation regime.

PMID- 17545240
TI  - Coupling of fast and slow modes in the reaction pathway of the minimal hammerhead
      ribozyme cleavage.
AB  - By employing classical molecular dynamics, correlation analysis of coupling
      between slow and fast dynamical modes, and free energy (umbrella) sampling using
      classical as well as mixed quantum mechanics molecular mechanics force fields, we
      uncover a possible pathway for phosphoryl transfer in the self-cleaving reaction
      of the minimal hammerhead ribozyme. The significance of this pathway is that it
      initiates from the minimal hammerhead crystal structure and describes the
      reaction landscape as a conformational rearrangement followed by a covalent
      transformation. The delineated mechanism is catalyzed by two metal (Mg(2+)) ions,
      proceeds via an in-line-attack by CYT 17 O2' on the scissile phosphorous (ADE 1.1
      P), and is therefore consistent with the experimentally observed inversion
      configuration. According to the delineated mechanism, the coupling between slow
      modes involving the hammerhead backbone with fast modes in the cleavage site
      appears to be crucial for setting up the in-line nucleophilic attack.

PMID- 17545242
TI  - Force-clamp spectroscopy of single-protein monomers reveals the individual
      unfolding and folding pathways of I27 and ubiquitin.
AB  - Single-protein force experiments have relied on a molecular fingerprint based on
      tethering multiple single-protein domains in a polyprotein chain. However,
      correlations between these domains remain an issue in interpreting force
      spectroscopy data, particularly during protein folding. Here we first show that
      force-clamp spectroscopy is a sensitive technique that provides a molecular
      fingerprint based on the unfolding step size of four single-monomer proteins. We
      then measure the force-dependent unfolding rate kinetics of ubiquitin and I27
      monomers and find a good agreement with the data obtained for the respective
      polyproteins over a wide range of forces, in support of the Markovian hypothesis.
      Moreover, with a large statistical ensemble at a single force, we show that
      ubiquitin monomers also exhibit a broad distribution of unfolding times as a
      signature of disorder in the folded protein landscape. Furthermore, we readily
      capture the folding trajectories of monomers that exhibit the same stages in
      folding observed for polyproteins, thus eliminating the possibility of entropic
      masking by other unfolded modules in the chain or domain-domain interactions. On
      average, the time to reach the I27 folded length increases with increasing
      quenching force at a rate similar to that of the polyproteins. Force-clamp
      spectroscopy at the single-monomer level reproduces the kinetics of unfolding and
      refolding measured using polyproteins, which proves that there is no mechanical
      effect of tethering proteins to one another in the case of ubiquitin and I27.

PMID- 17545243
TI  - Electrostatic domino effect in the Shaker K channel turret.
AB  - Voltage-gated K channels are regulated by extracellular divalent cations such as
      Mg(2+) and Sr(2+), either by screening of fixed negative surface charges, by
      binding directly or close to the voltage sensor, or by binding to the pore.
      Different K channels display different sensitivity to divalent cations. For
      instance, 20 mM MgCl(2) shifts the conductance versus voltage curve, G(V), of the
      Kv1-type Shaker channel with 14 mV, while the G(V) of Kv2.1 is shifted only with
      7 mV. This shift difference is paralleled with different working ranges. Kv1-type
      channels open at approximately -20 mV and Kv2.1 channel open at approximately +5
      mV. The aim of this study was to identify critical residues for this Mg(2+)
      induced G(V) shift by introducing Kv2.1 channel residues in the Shaker K channel.
      The K channels were expressed in Xenopus laevis oocytes and studied with the two
      electrode voltage-clamp technique. We found that three neutral-to-positive amino
      acid residue exchanges in the extracellular loops connecting transmembrane
      segments S5 and S6 transferred the Mg(2+)-shifting properties. The contributions
      of the three residues were additive, and thus independent of each other, with the
      contributions in the order 425 > 419 > 451. Charging 425 and 419 not only affect
      the Mg(2+)-induced G(V) shift with 5-6 mV, but also shifts the G(V) with 17 mV.
      Thus, a few strategically placed surface charges clearly modulate the channel's
      working range. Residue 425, located at some distance away from the voltage
      sensor, was shown to electrostatically affect residue K427, which in turn affects
      the voltage sensor S4-thus, an electrostatic domino effect.

PMID- 17545244
TI  - Serial perturbation of MinK in IKs implies an alpha-helical transmembrane span
      traversing the channel corpus.
AB  - I(Ks) channels contain four pore-forming KCNQ1 subunits and two accessory MinK
      subunits. MinK influences surface expression, voltage-dependence of gating,
      conduction, and pharmacology to yield the attributes characteristic of native
      channels in heart. The structure and location of the MinK transmembrane domain
      (TMD) remains a matter of scrutiny. As perturbation of gating analysis has
      correctly inferred the peripheral location and alpha-helical nature of TMDs in
      pore-forming subunits, the method is applied here to human MinK. Tryptophan and
      Asparagine substitution at 23 consecutive sites yields perturbation with alpha
      helical periodicity (residues 44-56) followed by an alternating impact pattern
      (residues 56-63). Arginine substitution across the span suggests that as few as
      eight sites are occluded from aqueous solution (residues 50-57). We favor a TMD
      model that is alpha-helical with the external portion of the span at a lipid
      protein boundary and the inner portion within the channel corpus in complex
      interactions.

PMID- 17545245
TI  - The chromophore structures of the Pr States in plant and bacterial phytochromes.
AB  - The resonance Raman spectra of the Pr state of the N-terminal 65-kDa fragment of
      plant phytochrome phyA have been measured and analyzed in terms of the
      configuration and conformation of the tetrapyrroles methine bridges. Spectra were
      obtained from phyA adducts reconstituted with the natural chromophore
      phytochromobilin as well as phycocyanobilin and its isotopomers labeled at the
      terminal methine bridges through (13)C/(12)C and D/H substitution. Upon comparing
      the resonance Raman spectra of the various phyA adducts, it was possible to
      identify the bands that originate from normal modes dominated by the stretching
      coordinates of the terminal methine bridges A-B and C-D. Quantum chemical
      calculations of the isolated tetrapyrroles reveal that these modes are sensitive
      indicators for the methine bridge configuration and conformation. For all phyA
      adducts, the experimental spectra of Pr including this marker band region are
      well reproduced by the calculated spectra obtained for the ZZZasa configuration.
      In contrast, there are substantial discrepancies between the experimental spectra
      and the spectra calculated for the ZZZssa configuration, which has been
      previously shown to be the chromophore geometry in the Pr state of the bacterial,
      biliverdin-binding phytochrome from Deinococcus radiodurans (Wagner, J. R., J. S.
      Brunzelle, K. T. Forest, R. D. Vierstra. 2005. Nature. 438:325-331). The results
      of this work, therefore, suggest that plant and bacterial (biliverdin-binding)
      phytochromes exhibit different structures in the parent state although the
      mechanism of the photoinduced reaction cycle may be quite similar.

PMID- 17545246
TI  - Folding and unfolding of gammaTIM monomers and dimers.
AB  - Kinetic simulations of the folding and unfolding of triosephosphate isomerase
      (TIM) from yeast were conducted using a single monomer gammaTIM polypeptide chain
      that folds as a monomer and two gammaTIM chains that fold to the native dimer
      structure. The basic protein model used was a minimalist Go model using the
      native structure to determine attractive energies in the protein chain. For each
      simulation type--monomer unfolding, monomer refolding, dimer unfolding, and dimer
      refolding--thirty simulations were conducted, successfully capturing each
      reaction in full. Analysis of the simulations demonstrates four main conclusions.
      First, all four simulation types have a similar "folding order", i.e., they have
      similar structures in intermediate stages of folding between the unfolded and
      folded state. Second, despite this similarity, different intermediate stages are
      more or less populated in the four different simulations, with 1), no
      intermediates populated in monomer unfolding; 2), two intermediates populated
      with beta(2)-beta(4) and beta(1)-beta(5) regions folded in monomer refolding; 3),
      two intermediates populated with beta(2)-beta(3) and beta(2)-beta(4) regions
      folded in dimer unfolding; and 4), two intermediates populated with beta(1)
      beta(5) and beta(1)-beta(5) + beta(6) + beta(7) + beta(8) regions folded in dimer
      refolding. Third, simulations demonstrate that dimer binding and unbinding can
      occur early in the folding process before complete monomer-chain folding. Fourth,
      excellent agreement is found between the simulations and MPAX (misincorporation
      proton alkyl exchange) experiments. In total, this agreement demonstrates that
      the computational Go model is accurate for gammaTIM and that the energy landscape
      of gammaTIM appears funneled to the native state.

PMID- 17545247
TI  - The low-energy forms of photosystem I light-harvesting complexes: spectroscopic
      properties and pigment-pigment interaction characteristics.
AB  - In this work the spectroscopic properties of the special low-energy absorption
      bands of the outer antenna complexes of higher plant Photosystem I have been
      investigated by means of low-temperature absorption, fluorescence, and
      fluorescence line-narrowing experiments. It was found that the red-most
      absorption bands of Lhca3, Lhca4, and Lhca1-4 peak, respectively, at 704, 708,
      and 709 nm and are responsible for 725-, 733-, and 732-nm fluorescence emission
      bands. These bands are more red shifted compared to "normal" chlorophyll a (Chl
      a) bands present in light-harvesting complexes. The low-energy forms are
      characterized by a very large bandwidth (400-450 cm(-1)), which is the result of
      both large homogeneous and inhomogeneous broadening. The observed optical
      reorganization energy is untypical for Chl a and resembles more that of BChl a
      antenna systems. The large broadening and the changes in optical reorganization
      energy are explained by a mixing of an Lhca excitonic state with a charge
      transfer state. Such a charge transfer state can be stabilized by the polar
      residues around Chl 1025. It is shown that the optical reorganization energy is
      changing through the inhomogeneous distribution of the red-most absorption band,
      with the pigments contributing to the red part of the distribution showing higher
      values. A second red emission form in Lhca4 was detected at 705 nm and originates
      from a broad absorption band peaking at 690 nm. This fluorescence emission is
      present also in the Lhca4-N-47H mutant, which lacks the 733-nm emission band.

PMID- 17545248
TI  - Calcium block of single sodium channels: role of a pore-lining aromatic residue.
AB  - Extracellular Ca(2+) ions cause a rapid block of voltage-gated sodium channels,
      manifest as an apparent reduction of the amplitude of single-channel currents. We
      examined the influence of residue Tyr-401 in the isoform rNa(V)1.4 on both single
      channel conductance and Ca(2+) block. An aromatic residue at this position in the
      outer mouth of the pore plays a critical role in high-affinity block by the
      guanidinium toxin tetrodotoxin, primarily due to an electrostatic attraction
      between the cationic blocker and the system of pi electrons on the aromatic face.
      We tested whether a similar attraction between small metal cations (Na(+) and
      Ca(2+)) and this residue would enhance single-channel conductance or pore block,
      using a series of fluorinated derivatives of phenylalanine at this position. Our
      results show a monotonic decrease in Ca(2+) block as the aromatic ring is
      increasingly fluorinated, a result in accord with a cation-pi interaction between
      Ca(2+) and the aromatic ring. This occurred without a change of single-channel
      conductance, consistent with a greater electrostatic effect of the pi system on
      divalent than on monovalent cations. High-level quantum mechanical calculations
      show that Ca(2+) ions likely do not bind directly to the aromatic ring because of
      the substantial energetic penalty of dehydrating a Ca(2+) ion. However, the
      complex of a Ca(2+) ion with its inner hydration shell, Ca(2+)(H(2)O)(6),
      interacts electrostatically with the aromatic ring in a way that affects the
      local concentration of Ca(2+) ions in the extracellular vestibule.

PMID- 17545249
TI  - Model-based definition of population heterogeneity and its effects on metabolism
      in sporulating Bacillus subtilis.
AB  - The soil bacterium Bacillus subtilis forms dormant, robust spores as a tactic to
      ensure survival under conditions of starvation. However, the sporulating culture
      includes sporulating and non-sporulating cells, because a portion of the cell
      population initiates sporulation in wild-type strain. We anticipated that the
      population effect must be considered carefully to analyse samples yielding
      population heterogeneity. We first built a mathematical model and simulated for
      signal transduction of the sporulation cue to see what mechanisms are responsible
      for generating the heterogeneity. The simulated results were confirmed
      experimentally, where heterogeneity is primarily modulated by negative feedback
      circuits, resulting in generation of a bistable response within the sporulating
      culture. We also confirmed that mutants relevant to negative feedback yield
      either sporulating or non-sporulating subpopulations. To see the effect of
      molecular mechanism between sporulating and non-sporulating cells in distinct
      manner, metabolome analysis was conducted using the above mutants. The metabolic
      profiles exhibited distinct characteristics with time regardless of whether
      sporulation was initiated or not. In addition, several distinct characteristics
      of metabolites were observed between strains, which was inconsistent with
      previously reported data. The results imply that careful consideration must be
      made in the interpretation of data obtained from cells yielding population
      heterogeneity.

PMID- 17545250
TI  - The cooperative role of OsCnfU-1A domain I and domain II in the iron sulphur
      cluster transfer process as revealed by NMR.
AB  - OsCnfU-1A is a chloroplast-type Nfu-like protein that consists of tandem repeats
      sharing high sequence homology. Domain I of this protein, but not domain II, has
      a C-X-X-C motif that is thought to assemble an iron-sulphur cluster. Herein we
      report the solution structure of OsCnfU-1A domain I (73-153). Although OsCnfU-1A
      domain I is structurally similar to OsCnfU-1A domain II (154-226), the
      electrostatic surface potential of the 2 domains differs. Domain I has an acidic
      surface, whereas that of domain II is predominantly basic. Chemical shift
      perturbation studies on OsCnfU-1A domain I and domain II with ferredoxin revealed
      negligible chemical shift changes in domain I, whereas much larger chemical shift
      changes were observed in domain II. The residues with larger chemical shift
      changes were located on the basic surface of domain II. Considering that
      ferredoxin is predominantly negatively charged, we propose the following
      hypothesis: First, an iron-sulphur cluster is assembled on domain I. Next, domain
      II interacts with the ferredoxin, thus tethering domain I close to the
      ferredoxin. Finally, domain I transfers the iron-sulphur cluster to the
      ferredoxin. Thus, domain II facilitates the efficient transfer of the iron
      sulphur cluster from domain I to the ferredoxin.

PMID- 17545251
TI  - Purification and characterization of tributyltin-binding protein type 2 from
      plasma of Japanese flounder, Paralichthys olivaceus.
AB  - We used gel filtration chromatography, anion-exchange chromatography and
      polyacrylamide gel electrophoresis to purify tributyltin-binding protein type 2
      (TBT-bp 2) from plasma of Japanese flounder (Paralichthys olivaceus) injected
      intraperitoneally with TBT (5.0 mg/kg body weight). Sodium dodecyl sulfate
      polyacrylamide gel electrophoresis indicated that the molecular mass of TBT-bp 2
      was approximately 48 kDa, and isoelectric focusing-polyacrylamide gel
      electrophoresis indicated that the isoelectric point was approximately 3.0. TBT
      bp 2 contained 40% N-glycan. The complete cDNA nucleotide sequence and the genome
      sequence of TBT-bp 2 were determined by means of rapid amplification of cDNA ends
      of liver tissue of Japanese flounder and a genome-walking technique,
      respectively. The 216 amino acid sequence of TBT-bp 2 showed 47% identity to the
      sequences of puffer fish (Takifugu pardalis) saxitoxin- and tetrodotoxin-binding
      protein but only 27% similarity to the sequence of TBT-bp 1. Analysis of the
      motif sequence of the amino acid sequence and the structure of the gene encoding
      TBT-bp 2 suggested that this protein belongs to the lipocalin superfamily.

PMID- 17545252
TI  - Patient satisfaction with health services in Bangladesh.
AB  - Concern over the quality of health care services in Bangladesh has led to loss of
      faith in public and private hospitals, low utilization of public health
      facilities, and increasing outflow of Bangladeshi patients to hospitals in
      neighbouring countries. Under the circumstances, assessment of the country's
      quality of health care service has become imperative, in which the patient's
      voice must begin to play a greater role. This study attempts to identify the
      determinants of patient satisfaction with public, private and foreign hospitals.
      A survey was conducted involving inpatients in public and private hospitals in
      Dhaka City and patients who have experienced hospital services in a foreign
      country. Their views were obtained through exit polls using probability and non
      probability (for foreign hospital patients) sampling procedures. Regression
      models were derived to identify key factors influencing patient satisfaction in
      the different types of hospitals. Doctors' service orientation, a composite of 13
      measures, is the most important factor explaining patient satisfaction. Policy
      implications are discussed.

PMID- 17545253
TI  - Caring for Ms. Class II Amalgam.

PMID- 17545254
TI  - Anesthetic study questioned.

PMID- 17545255
TI  - Continuing dental education.

PMID- 17545256
TI  - Metabolic syndrome.

PMID- 17545257
TI  - TMD debate.

PMID- 17545258
TI  - More about TMD.

PMID- 17545263
TI  - Prevention of infective endocarditis: guidelines from the American Heart
      Association: a guideline from the American Heart Association Rheumatic Fever,
      Endocarditis and Kawasaki Disease Committee, Council on Cardiovascular Disease in
      the Young, and the Council on Clinical Cardiology, Council on Cardiovascular
      Surgery and Anesthesia, and the Quality of Care and Outcomes Research
      Interdisciplinary Working Group.
AB  - BACKGROUND: The purpose of this statement is to update the recommendations by the
      American Heart Association (AHA) for the prevention of infective endocarditis,
      which were last published in 1997. METHODS AND RESULTS: A writing group appointed
      by the AHA for their expertise in prevention and treatment of infective
      endocarditis (IE) with liaison members representing the American Dental
      Association, the Infectious Diseases Society of America and the American Academy
      of Pediatrics. The writing group reviewed input from national and international
      experts on IE. The recommendations in this document reflect analyses of relevant
      literature regarding procedure-related bacteremia and IE; in vitro susceptibility
      data of the most common microorganisms, which cause IE; results of prophylactic
      studies in animal models of experimental endocarditis; and retrospective and
      prospective studies of prevention of IE. MEDLINE database searches from 1950
      through 2006 were done for English language articles using the following search
      terms: endocarditis, infective endocarditis, prophylaxis, prevention, antibiotic,
      antimicrobial, pathogens, organisms, dental, gastrointestinal, genitourinary,
      streptococcus, enterococcus, staphylococcus, respiratory, dental surgery,
      pathogenesis, vaccine, immunization and bacteremia. The reference lists of the
      identified articles were also searched. The writing group also searched the AHA
      online library. The American College of Cardiology/AHA classification of
      recommendations and levels of evidence for practice guidelines were used. The
      article subsequently was reviewed by outside experts not affiliated with the
      writing group and by the AHA Science Advisory and Coordinating Committee.
      CONCLUSIONS: The major changes in the updated recommendations include the
      following. (1) The committee concluded that only an extremely small number of
      cases of IE might be prevented by antibiotic prophylaxis for dental procedures
      even if such prophylactic therapy were 100 percent effective. (2) IE prophylaxis
      for dental procedures should be recommended only for patients with underlying
      cardiac conditions associated with the highest risk of adverse outcome from IE.
      (3) For patients with these underlying cardiac conditions, prophylaxis is
      recommended for all dental procedures that involve manipulation of gingival
      tissue or the periapical region of teeth or perforation of the oral mucosa. (4)
      Prophylaxis is not recommended based solely on an increased lifetime risk of
      acquisition of IE. (5) Administration of antibiotics solely to prevent
      endocarditis is not recommended for patients who undergo a genitourinary or
      gastrointestinal tract procedure. These changes are intended to define more
      clearly when IE prophylaxis is or is not recommended and to provide more uniform
      and consistent global recommendations.

PMID- 17545264
TI  - A legal perspective on antibiotic prophylaxis.

PMID- 17545265
TI  - The longevity of amalgam versus compomer/composite restorations in posterior
      primary and permanent teeth: findings From the New England Children's Amalgam
      Trial.
AB  - BACKGROUND: Limited information is available from randomized clinical trials
      comparing the longevity of amalgam and resin-based compomer/composite
      restorations. The authors compared replacement rates of these types of
      restorations in posterior teeth during the five-year follow-up of the New England
      Children's Amalgam Trial. METHODS: The authors randomized children aged 6 to 10
      years who had two or more posterior occlusal carious lesions into groups that
      received amalgam (n=267) or compomer (primary teeth)/composite (permanent teeth)
      (n=267) restorations and followed them up semiannually. They compared the
      longevity of restorations placed on all posterior surfaces using random effects
      survival analysis. RESULTS: The average+/-standard deviation follow-up was 2.8+/
      1.4 years for primary tooth restorations and 3.4+/-1.9 years for permanent tooth
      restorations. In primary teeth, the replacement rate was 5.8 percent of compomers
      versus 4.0 percent of amalgams (P=.10), with 3.0 percent versus 0.5 percent
      (P=.002), respectively, due to recurrent caries. In permanent teeth, the
      replacement rate was 14.9 percent of composites versus 10.8 percent of amalgams
      (P=.45), and the repair rate was 2.8 percent of composites versus 0.4 percent of
      amalgams (P=.02). CONCLUSION: Although the overall difference in longevity was
      not statistically significant, compomer was replaced significantly more
      frequently owing to recurrent caries, and composite restorations required seven
      times as many repairs as did amalgam restorations. CLINICAL IMPLICATIONS:
      Compomer/composite restorations on posterior tooth surfaces in children may
      require replacement or repair at higher rates than amalgam restorations, even
      within five years of placement.

PMID- 17545266
TI  - Survival and reasons for failure of amalgam versus composite posterior
      restorations placed in a randomized clinical trial.
AB  - BACKGROUND: Failure of dental restorations is a major concern in dental practice.
      Replacement of failed restorations constitutes the majority of operative work.
      Clinicians should be aware of the longevity of, and likely reasons for the
      failure of, direct posterior restorations. In a long-term, randomized clinical
      trial, the authors compared the longevity of amalgam and composite. SUBJECTS,
      METHODS AND MATERIALS: The authors randomly assigned one-half of the 472
      subjects, whose age ranged from 8 through 12 years, to receive amalgam
      restorations in posterior teeth and the other one-half to receive resin-based
      composite restorations. Study dentists saw subjects annually to conduct follow-up
      oral examinations and take bitewing radiographs. Restorations needing replacement
      were failures. The dentists recorded differential reasons for restoration
      failure. RESULTS: Subjects received a total of 1,748 restorations at baseline,
      which the authors followed for up to seven years. Overall, 10.1 percent of the
      baseline restorations failed. The survival rate of the amalgam restorations was
      94.4 percent; that of composite restorations was 85.5 percent. Annual failure
      rates ranged from 0.16 to 2.83 percent for amalgam restorations and from 0.94 to
      9.43 percent for composite restorations. Secondary caries was the main reason for
      failure in both materials. Risk of secondary caries was 3.5 times greater in the
      composite group. CONCLUSION: Amalgam restorations performed better than did
      composite restorations. The difference in performance was accentuated in large
      restorations and in those with more than three surfaces involved. CLINICAL
      IMPLICATIONS: Use of amalgam appears to be preferable to use of composites in
      multisurface restorations of large posterior teeth if longevity is the primary
      criterion in material selection.

PMID- 17545267
TI  - Replacement of a fixed partial denture secondary to abutment fracture.
AB  - BACKGROUND: The authors present a case that demonstrates the efficient
      replacement of a fixed prosthesis after a patient's abutment tooth fractured and
      required extraction. The fractured tooth had a local infection, and the maxillary
      bone was low-density and limited in height. CASE DESCRIPTION: The authors removed
      the tooth and grafted the site with particulate bone, while concurrently placing
      two implants in the edentulous region. After four months, they placed one
      additional implant and secured a fixed provisional prosthesis within one week.
      CLINICAL IMPLICATIONS: The patient wanted to minimize the time that she would
      have to be without a fixed prosthesis. The authors met her expectations by using
      an accelerated treatment plan.

PMID- 17545268
TI  - Osteoid osteoma of the zygoma: report of an unusual case.
AB  - BACKGROUND: Osteoid osteoma is a benign tumor of bone characterized by pain,
      usually occurring at night, that shows a dramatic response to aspirin. The
      literature contains reports of only a few cases in the head and neck region. CASE
      DESCRIPTION: The authors present an unusual case of an osteoid osteoma of the
      craniofacial bones. The patient sought an evaluation of pain in the area of the
      right zygoma. One of the authors, an oral and maxillofacial surgeon, noted a
      small area of swelling. The patient underwent radiographic, computed tomographic
      and nuclear medicine studies. On the basis of the images and the biopsy report,
      the authors made a diagnosis of osteoid osteoma. In this article, they describe
      the treatment of and new modalities of therapy for this condition. CLINICAL
      IMPLICATIONS: The general dentist should be aware of any lesion that is not
      common. If the generalist has any doubt about the nature or management of an
      unusual oral lesion, referral to appropriate specialists is mandatory.

PMID- 17545269
TI  - Screening for cardiovascular risk factors in a dental setting.
AB  - BACKGROUND: The authors assessed the utilization of oral health care
      professionals (OHCPs) as a resource for identifying patients who were unaware of
      their increased risk of developing cardiovascular disease (CVD). METHODS: OHCPs
      administered a CVD risk-screening questionnaire, measured blood pressure and
      tested cholesterol levels, high-density lipoprotein levels and hemoglobin A1c
      (HgA1c) levels using "finger-stick" blood testing in 100 patients treated in a
      dental school clinic who were unaware of their CVD risk status. The authors
      determined the prevalence of specific risk factors (that is, smoking and abnormal
      levels of systolic blood pressure, lipids, body mass index and HgA1c) and
      calculated Framingham 10-year coronary heart disease (CHD) risk scores. RESULTS:
      Seventeen percent of the 100 patients (35 percent of men, 5 percent of women) had
      an increased global risk of experiencing a CHD event within 10 years (Framingham
      risk score>10 percent). Seventy-three percent of participants had one or more
      risk factors and 31 percent had two or more risk factors present. More men than
      women had low levels of high-density lipoprotein (45 percent [18/40] of men
      versus 3.3 percent [2/60] of women; P<.0001). The mean Framingham CHD risk score
      increased with increasing risk factor burden. CONCLUSIONS: OHCPs identified
      patients with an increased CHD risk who could benefit from primary prevention
      activities. A substantial proportion of study patients who were unaware of their
      risk status were at an increased risk of experiencing a CHD event within 10
      years. OHCPs could contribute to public health CHD control efforts.

PMID- 17545270
TI  - Patients' satisfaction with dental esthetics.
AB  - BACKGROUND: Esthetics has become an important issue in modern society, as it
      seems to define one's character. In the past, functional demands were the main
      consideration in dental treatment. Today, with the decrease in caries prevalence,
      the focus has shifted toward dental esthetics. The authors conducted a study to
      evaluate the factors influencing patients' satisfaction with their dental
      appearance and with the results of esthetic treatment. METHODS: The authors
      surveyed a population of 407 adults (mean age, 21 years). They distributed a
      questionnaire regarding satisfaction with current dental esthetics and previous
      esthetic treatments. RESULTS: Of the 407 subjects, 152 (37.3 percent) were
      dissatisfied with their dental appearance. Tooth color was the primary reason for
      dissatisfaction (133 [89.3 percent] of 149 subjects), followed by poor tooth
      alignment (36 [23.7 percent] of 152 subjects), although 110 (27 percent) of the
      407 subjects had received orthodontic treatment. The authors found no correlation
      between patients' satisfaction with their dental appearance and having undergone
      any procedure to whiten their teeth. Nevertheless, 134 (88.2 percent) of the
      dissatisfied subjects reported that they would like to undergo this procedure.
      CONCLUSIONS: Tooth color was a major factor with regard to dental esthetics. Most
      subjects were interested in improving their appearance and whitening their teeth.
      CLINICAL IMPLICATIONS: When planning treatment, dentists should take into
      consideration esthetic objectives in addition to function, structure and biology.
      This requires the clinician to rely on several disciplines in dentistry to
      deliver the highest level of dental care, which should lead to a higher level of
      patient satisfaction.

PMID- 17545271
TI  - Predictors of variation in mandibular incisor enamel thickness.
AB  - BACKGROUND: Interproximal reduction of mandibular incisor enamel often is
      performed as an adjunct to orthodontic alignment. The authors conducted a study
      to determine factors contributing to variations in incisor enamel thickness.
      METHODS: The authors compared enamel thickness between mandibular central and
      lateral incisors, between mesial and distal surfaces, between male and female
      subjects (N=40 each) and between African-American and white subjects (N=40 each).
      The authors also evaluated correlations between overall tooth width and enamel
      thickness. RESULTS: The authors found significantly greater enamel thickness in
      lateral incisors, on distal tooth surfaces and in black subjects (P<.0001 for
      each); they found no differences between male and female subjects. They found
      that wider teeth were associated with greater enamel thickness (P<.01) but that
      the amount of thickness varied greatly among subjects (range: 0.44-1.28
      millimeters). CONCLUSIONS: Thicker enamel was found on the distal aspect of
      lateral incisors, in black subjects and in wider teeth. The authors observed,
      however, that the variations in thickness are not fully explained by these
      factors alone. CLINICAL IMPLICATIONS: If substantial enamel reduction is planned
      as part of dental treatment, the authors recommend that clinicians use calibrated
      radiographs to measure the thickness of their patients' enamel surfaces because
      of the extensive variation in enamel thickness among and within people.

PMID- 17545272
TI  - Should resin cements be used for every cementation?

PMID- 17545273
TI  - The dentist as chief executive officer.

PMID- 17545274
TI  - Is it ethical to have more than one fee schedule?

PMID- 17545275
TI  - For the dental patient...: antibiotics and your heart: new guidelines from the
      American Heart Association.

PMID- 17545276
TI  - Acid reflux into the oesophagus does not influence exercise-induced airway
      narrowing in bronchial asthma.
AB  - OBJECTIVES: A few studies on small patient series have investigated the
      relationship between gastroesophageal reflux and bronchial responsiveness as
      expressed by exercise-induced bronchoconstriction (EIB), with non-conclusive
      results. The aim of this study was to evaluate whether the presence of acid in
      the oesophagus may influence EIB. METHODS: 45 patients with bronchial asthma
      underwent spirometry, exercise challenge on bicycle ergometer and 24 h
      oesophageal pH monitoring. Subjects with EIB (Forced expiratory volume in the
      first second (FEV1)) percentage decrease after exercise (DeltaFEV1) > or =15%, n
      = 28) were retested after a 2 week treatment course with omeprazole 40 mg/daily.
      Exercise at baseline was performed at the same time as oesophageal pH monitoring.
      RESULTS: In basal condition, there was no difference in FEV1, acid exposure time
      or number of refluxes measured during 24 h pH monitoring between patients with
      and without EIB. There was no relationship between spirometry results and
      DeltaFEV1 on one hand, and parameters of gastroesophageal reflux on the other.
      Nine patients with EIB (31.0%) and six patients without EIB (37.5%) had one or
      more episodes of GER during exercise challenge, without significant differences
      between the two groups. After gastric acid inhibition by omeprazole, DeltaFEV1
      did not change significantly. CONCLUSIONS: The results indicate that acid in the
      oesophagus, or its short-term inhibition by proton pump inhibitors, has no
      influence on exercise-induced bronchoconstriction.

PMID- 17545278
TI  - The maintenance of human CD4+ CD25+ regulatory T cell function: IL-2, IL-4, IL-7
      and IL-15 preserve optimal suppressive potency in vitro.
AB  - CD4+ CD25+ regulatory T cells (Tregs) have far-reaching immunotherapeutic
      applications, the realization of which will require a greater understanding of
      the factors influencing their function and phenotype during ex vivo manipulation.
      In murine models, IL-2 plays an important role in both the maintenance of a
      functional Treg population in vivo and the activation of suppression in vitro. We
      have found that IL-2 maintains optimal function of human CD4+ CD25+ Tregs in
      vitro and increases expression of both forkhead box protein 3, human nomenclature
      (FOXP3) and the distinctive markers CD25, cytotoxic T lymphocyte antigen-4 (CTLA
      4) and glucocorticoid-induced tumor necrosis factor receptor superfamily member
      number 18 (GITR). Although IL-2 reduced spontaneous apoptosis of Tregs, this
      property alone could not account for the optimal maintenance of the regulatory
      phenotype. The inhibition of phosphatidylinositol 3-kinase (PI3K) signaling by
      LY294002, a chemical inhibitor of PI3K, abolished the maintenance of maximal
      suppressive potency by IL-2, yet had no effect on the up-regulation of FOXP3,
      CD25, CTLA-4 and GITR. Other common gamma chain (gammac) cytokines-IL-4, IL-7 and
      IL-15-had similar properties, although IL-4 showed a unique lack of effect on the
      expression of FOXP3 or Treg markers despite maintaining maximal regulatory
      function. Taken together, our data suggest a model in which the gammac cytokines
      IL-2, IL-4, IL-7 and IL-15 maintain the optimal regulatory function of human CD4+
      CD25+ T cells in a PI3K-dependent manner, offering new insight into the effective
      manipulation of Tregs ex vivo.

PMID- 17545279
TI  - The CD8 T cell response to vaccinia virus exhibits site-dependent heterogeneity
      of functional responses.
AB  - CD8 T cell responses to vaccinia virus (VV) and a virus-encoded ovalbumin peptide
      (OVAP) epitope were examined using adoptively transferred OT-I T cells. The
      results demonstrate that upon intra-peritoneal challenge with ovalbumin
      expressing VV (VV-OVAP), OT-I T cell proliferation occurs initially in lymph
      nodes and spleens followed by migration of the divided cells to the peritoneal
      cavity. Massive clonal expansion occurs in response to both the virus and the
      virus-encoded ovalbumin (OVA) epitope, as demonstrated using low numbers of
      adoptively transferred cells, and the responding OT-I cells display marked site
      dependent functional heterogeneity with respect to IFN-gamma and tumor necrosis
      factor-alpha (TNF-alpha) production and granzyme B expression. OT-I cells
      responding to VV-OVAP develop the capacity to produce IFN-gamma in response to
      antigen as they proliferate and differentiate. In marked contrast, naive OT-I
      cells rapidly produce TNF-alpha upon antigen recognition, and this capacity
      declines as the cells proliferate in response to the virus, suggesting that this
      potent inflammatory cytokine may be important primarily during initiation of the
      response. At the peak of clonal expansion, a large fraction (30-60%) of the OT-I
      cells responding to the virus express high IL-7Ralpha levels, and the majority of
      these cells is subsequently lost. While high IL-7Ralpha expression may be
      necessary for a CD8 T cell to transition to memory, it is clearly not sufficient.
      Thus, OT-I cells responding to VV infection exhibit a high degree of
      heterogeneity within the responding population that differs depending on their
      anatomical location, despite the specificity and affinity of the TCR being
      identical on all of the cells.

PMID- 17545280
TI  - Structure and function of cold shock proteins in archaea.
AB  - Archaea are abundant and drive critical microbial processes in the Earth's cold
      biosphere. Despite this, not enough is known about the molecular mechanisms of
      cold adaptation and no biochemical studies have been performed on
      stenopsychrophilic archaea (e.g., Methanogenium frigidum). This study examined
      the structural and functional properties of cold shock proteins (Csps) from
      archaea, including biochemical analysis of the Csp from M. frigidum. csp genes
      are present in most bacteria and some eucarya but absent from most archaeal
      genome sequences, most notably, those of all archaeal thermophiles and
      hyperthermophiles. In bacteria, Csps are small, nucleic acid binding proteins
      involved in a variety of cellular processes, such as transcription. In this
      study, archaeal Csp function was assessed by examining the ability of csp genes
      from psychrophilic and mesophilic Euryarchaeota and Crenarchaeota to complement a
      cold-sensitive growth defect in Escherichia coli. In addition, an archaeal gene
      with a cold shock domain (CSD) fold but little sequence identity to Csps was also
      examined. Genes encoding Csps or a CSD structural analog from three psychrophilic
      archaea rescued the E. coli growth defect. The three proteins were predicted to
      have a higher content of solvent-exposed basic residues than the noncomplementing
      proteins, and the basic residues were located on the nucleic acid binding
      surface, similar to their arrangement in E. coli CspA. The M. frigidum Csp was
      purified and found to be a single-domain protein that folds by a reversible two
      state mechanism and to exhibit a low conformational stability typical of cold
      adapted proteins. Moreover, M. frigidum Csp was characterized as binding E. coli
      single-stranded RNA, consistent with its ability to complement function in E.
      coli. The studies show that some Csp and CSD fold proteins have retained
      sufficient similarity throughout evolution in the Archaea to be able to function
      effectively in the Bacteria and that the function of the archaeal proteins
      relates to cold adaptation. The initial biochemical analysis of M. frigidum Csp
      has developed a platform for further characterization and demonstrates the
      potential for expanding molecular studies of proteins from this important
      archaeal stenopsychrophile.

PMID- 17545281
TI  - Protein modulator of multidrug efflux gene expression in Pseudomonas aeruginosa.
AB  - nalC multidrug-resistant mutants of Pseudomonas aeruginosa show enhanced
      expression of the mexAB-oprM multidrug efflux system as a direct result of the
      production of a ca. 6,100-Da protein, PA3719, in these mutants. Using a bacterial
      two-hybrid system, PA3719 was shown to interact in vivo with MexR, a repressor of
      mexAB-oprM expression. Isothermal titration calorimetry (ITC) studies confirmed a
      high-affinity interaction (equilibrium dissociation constant [K(D)], 158.0 +/-
      18.1 nM) of PA3719 with MexR in vitro. PA3719 binding to and formation of a
      complex with MexR obviated repressor binding to its operator, which overlaps the
      efflux operon promoter, suggesting that mexAB-oprM hyperexpression in nalC
      mutants results from PA3719 modulation of MexR repressor activity. Consistent
      with this, MexR repression of mexA transcription in an in vitro transcription
      assay was alleviated by PA3719. Mutations in MexR compromising its interaction
      with PA3719 in vivo were isolated and shown to be located internally and
      distributed throughout the protein, suggesting that they impacted PA3719 binding
      by altering MexR structure or conformation rather than by having residues
      interacting specifically with PA3719. Four of six mutant MexR proteins studied
      retained repressor activity even in a nalC strain producing PA3719. Again, this
      is consistent with a PA3719 interaction with MexR being necessary to obviate MexR
      repressor activity. The gene encoding PA3719 has thus been renamed armR
      (antirepressor for MexR). A representative "noninteracting" mutant MexR protein,
      MexR(I104F), was purified, and ITC confirmed that it bound PA3719 with reduced
      affinity (5.4-fold reduced; K(D), 853.2 +/- 151.1 nM). Consistent with this,
      MexR(I104F) repressor activity, as assessed using the in vitro transcription
      assay, was only weakly compromised by PA3719. Finally, two mutations (L36P and
      W45A) in ArmR compromising its interaction with MexR have been isolated and
      mapped to a putative C-terminal alpha-helix of the protein that alone is
      sufficient for interaction with MexR.

PMID- 17545282
TI  - The first agmatine/cadaverine aminopropyl transferase: biochemical and structural
      characterization of an enzyme involved in polyamine biosynthesis in the
      hyperthermophilic archaeon Pyrococcus furiosus.
AB  - We report here the characterization of the first agmatine/cadaverine aminopropyl
      transferase (ACAPT), the enzyme responsible for polyamine biosynthesis from an
      archaeon. The gene PF0127 encoding ACAPT in the hyperthermophile Pyrococcus
      furiosus was cloned and expressed in Escherichia coli, and the recombinant
      protein was purified to homogeneity. P. furiosus ACAPT is a homodimer of 65 kDa.
      The broad substrate specificity of the enzyme toward the amine acceptors is
      unique, as agmatine, 1,3-diaminopropane, putrescine, cadaverine, and sym-nor
      spermidine all serve as substrates. While maximal catalytic activity was observed
      with cadaverine, agmatine was the preferred substrate on the basis of the
      k(cat)/K(m) value. P. furiosus ACAPT is thermoactive and thermostable with an
      apparent melting temperature of 108 degrees C that increases to 112 degrees C in
      the presence of cadaverine. Limited proteolysis indicated that the only
      proteolytic cleavage site is localized in the C-terminal region and that the C
      terminal peptide is not necessary for the integrity of the active site. The
      crystal structure of the enzyme determined to 1.8-A resolution confirmed its
      dimeric nature and provided insight into the proteolytic analyses as well as into
      mechanisms of thermal stability. Analysis of the polyamine content of P. furiosus
      showed that spermidine, cadaverine, and sym-nor-spermidine are the major
      components, with small amounts of sym-nor-spermine and N-(3
      aminopropyl)cadaverine (APC). This is the first report in Archaea of an unusual
      polyamine APC that is proposed to play a role in stress adaptation.

PMID- 17545283
TI  - Crystal structures of the receiver domain of the response regulator PhoP from
      Escherichia coli in the absence and presence of the phosphoryl analog
      beryllofluoride.
AB  - The response regulator PhoP is part of the PhoQ/PhoP two-component system
      involved in responses to depletion of extracellular Mg(2+). Here, we report the
      crystal structures of the receiver domain of Escherichia coli PhoP determined in
      the absence and presence of the phosphoryl analog beryllofluoride. In the
      presence of beryllofluoride, the active receiver domain forms a twofold symmetric
      dimer similar to that seen in structures of other regulatory domains from the
      OmpR/PhoB family, providing further evidence that members of this family utilize
      a common mode of dimerization in the active state. In the absence of activating
      agents, the PhoP receiver domain crystallizes with a similar structure,
      consistent with the previous observation that high concentrations can promote an
      active state of PhoP independent of phosphorylation.

PMID- 17545284
TI  - Cell-wide responses to low-oxygen exposure in Desulfovibrio vulgaris
      Hildenborough.
AB  - The responses of the anaerobic, sulfate-reducing organism Desulfovibrio vulgaris
      Hildenborough to low-oxygen exposure (0.1% O(2)) were monitored via
      transcriptomics and proteomics. Exposure to 0.1% O(2) caused a decrease in the
      growth rate without affecting viability. Concerted upregulation of the predicted
      peroxide stress response regulon (PerR) genes was observed in response to the
      0.1% O(2) exposure. Several of the candidates also showed increases in protein
      abundance. Among the remaining small number of transcript changes was the
      upregulation of the predicted transmembrane tetraheme cytochrome c(3) complex.
      Other known oxidative stress response candidates remained unchanged during the
      low-O(2) exposure. To fully understand the results of the 0.1% O(2) exposure,
      transcriptomics and proteomics data were collected for exposure to air using a
      similar experimental protocol. In contrast to the 0.1% O(2) exposure, air
      exposure was detrimental to both the growth rate and viability and caused
      dramatic changes at both the transcriptome and proteome levels. Interestingly,
      the transcripts of the predicted PerR regulon genes were downregulated during air
      exposure. Our results highlight the differences in the cell-wide responses to low
      and high O(2) levels in D. vulgaris and suggest that while exposure to air is
      highly detrimental to D. vulgaris, this bacterium can successfully cope with
      periodic exposure to low O(2) levels in its environment.

PMID- 17545285
TI  - The oligomeric state of c rings from cyanobacterial F-ATP synthases varies from
      13 to 15.
AB  - We isolated the c rings of F-ATP synthases from eight cyanobacterial strains
      belonging to four different taxonomic classes (Chroococcales, Nostocales,
      Oscillatoriales, and Gloeobacteria). These c rings showed different mobilities on
      sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), probably
      reflecting their molecular masses. This supposition was validated with the
      previously characterized c(11), c(14), and c(15) rings, which migrated on SDS
      PAGE in proportion to their molecular masses. Hence, the masses of the
      cyanobacterial c rings can conveniently be deduced from their electrophoretic
      mobilities and, together with the masses of the c monomers, allow the calculation
      of the c ring stoichiometries. The method is a simple and fast way to determine
      stoichiometries of SDS-stable c rings and hence a convenient means to
      unambiguously determine the ion-to-ATP ratio, a parameter reflecting the
      bioenergetic efficacy of F-ATP synthases. AFM imaging was used to prove the
      accuracy of the method and confirmed that the c ring of Synechococcus elongatus
      SAG 89.79 is a tridecameric oligomer. Despite the high conservation of the c
      subunit sequences from cyanobacterial strains from various environmental groups,
      the stoichiometries of their c rings varied between c(13) and c(15). This
      systematic study of the c-ring stoichiometries suggests that variability of c
      ring sizes might represent an adaptation of the individual cyanobacterial species
      to their particular environmental and physiological conditions. Furthermore, the
      two new examples of c(15) rings underline once more that an F(1)/F(o) symmetry
      mismatch is not an obligatory feature of all F-ATP synthases.

PMID- 17545286
TI  - The intracellular concentration of acetyl phosphate in Escherichia coli is
      sufficient for direct phosphorylation of two-component response regulators.
AB  - Acetyl phosphate, the intermediate of the AckA-Pta pathway, acts as a global
      signal in Escherichia coli. Although acetyl phosphate clearly signals through two
      component response regulators, it remains unclear whether acetyl phosphate acts
      as a direct phospho donor or functions through an indirect mechanism. We used two
      dimensional thin-layer chromatography to measure the relative concentrations of
      acetyl phosphate, acetyl coenzyme A, ATP, and GTP over the course of the entire
      growth curve. We estimated that the intracellular concentration of acetyl
      phosphate in wild-type cells reaches at least 3 mM, a concentration sufficient to
      activate two-component response regulators via direct phosphoryl transfer.

PMID- 17545287
TI  - Deletion of the parA (soj) homologue in Pseudomonas aeruginosa causes ParB
      instability and affects growth rate, chromosome segregation, and motility.
AB  - The parA and parB genes of Pseudomonas aeruginosa are located approximately 8 kb
      anticlockwise from oriC. ParA is a cytosolic protein present at a level of around
      600 molecules per cell in exponential phase, but the level drops about fivefold
      in stationary phase. Overproduction of full-length ParA or the N-terminal 85
      amino acids severely inhibits growth of P. aeruginosa and P. putida. Both
      inactivation of parA and overexpression of parA in trans in P. aeruginosa also
      lead to accumulation of anucleate cells and changes in motility. Inactivation of
      parA also increases the turnover rate (degradation) of ParB. This may provide a
      mechanism for controlling the level of ParB in response to the growth rate and
      expression of the parAB operon.

PMID- 17545288
TI  - Oxidative DNA damage defense systems in avoidance of stationary-phase mutagenesis
      in Pseudomonas putida.
AB  - Oxidative damage of DNA is a source of mutation in living cells. Although all
      organisms have evolved mechanisms of defense against oxidative damage, little is
      known about these mechanisms in nonenteric bacteria, including pseudomonads. Here
      we have studied the involvement of oxidized guanine (GO) repair enzymes and DNA
      protecting enzyme Dps in the avoidance of mutations in starving Pseudomonas
      putida. Additionally, we examined possible connections between the oxidative
      damage of DNA and involvement of the error-prone DNA polymerase (Pol)V homologue
      RulAB in stationary-phase mutagenesis in P. putida. Our results demonstrated that
      the GO repair enzymes MutY, MutM, and MutT are involved in the prevention of base
      substitution mutations in carbon-starved P. putida. Interestingly, the
      antimutator effect of MutT was dependent on the growth phase of bacteria.
      Although the lack of MutT caused a strong mutator phenotype under carbon
      starvation conditions for bacteria, only a twofold increased effect on the
      frequency of mutations was observed for growing bacteria. This indicates that
      MutT has a backup system which efficiently complements the absence of this enzyme
      in actively growing cells. The knockout of MutM affected only the spectrum of
      mutations but did not change mutation frequency. Dps is known to protect DNA from
      oxidative damage. We found that dps-defective P. putida cells were more sensitive
      to sudden exposure to hydrogen peroxide than wild-type cells. At the same time,
      the absence of Dps did not affect the accumulation of mutations in populations of
      starved bacteria. Thus, it is possible that the protective role of Dps becomes
      essential for genome integrity only when bacteria are exposed to exogenous agents
      that lead to oxidative DNA damage but not under physiological conditions.
      Introduction of the Y family DNA polymerase PolV homologue rulAB into P. putida
      increased the proportion of A-to-C and A-to-G base substitutions among mutations,
      which occurred under starvation conditions. Since PolV is known to perform
      translesion synthesis past damaged bases in DNA (e.g., some oxidized forms of
      adenine), our results may imply that adenine oxidation products are also an
      important source of mutation in starving bacteria.

PMID- 17545289
TI  - Regulation of carbon and nitrogen utilization by CbrAB and NtrBC two-component
      systems in Pseudomonas aeruginosa.
AB  - The global effect of the CbrAB and NtrBC two-component systems on the control of
      carbon and nitrogen utilization in Pseudomonas aeruginosa was characterized by
      phenotype microarray analyses with single and double mutants and the isogenic
      parent strain. The tested compounds were clustered based on the growth phenotypes
      of these strains, and the results clearly demonstrated the pivotal roles of CbrAB
      and NtrBC in carbon and nitrogen utilization, respectively. Growth of the cbrAB
      deletion mutant on arginine, histidine, and polyamines used as the sole carbon
      source was abolished, while growth on the tricarboxylic acid (TCA) cycle
      intermediates was sustained. In this study, suppressors of the cbr mutant were
      selected from minimal medium containing l-arginine as the sole carbon and
      nitrogen source. These mutants fell into two groups according to the ability to
      utilize histidine. The genomic library of a histidine-positive suppressor mutant
      was constructed, and the corresponding suppressor gene was identified by
      complementation as an ntrB allele. Similar results were obtained from four
      additional suppressor mutants, and point mutations of these ntrB alleles
      resulting in the following changes in residues were identified, with implications
      for reduced phosphatase activities: L126W, D227A, P228L, and S229I. The Ntr
      systems of these ntrB mutants became constitutively active, as revealed by the
      activity profiles of glutamate dehydrogenase, glutamate synthase, and glutamine
      synthetase. As a result, these mutants not only regain the substrate-specific
      induction on catabolic arginine and histidine operons but are also expressed to
      higher levels than the wild type. While the DeltacbrAB ntrB(Con) mutant restored
      growth on many N-containing compounds used as the carbon sources, its capability
      to grow on TCA cycle intermediates and glucose was compromised when ammonium
      served as the sole nitrogen source, mostly due to an extreme imbalance of carbon
      and nitrogen regulatory systems. In summary, this study supports the notion that
      CbrAB and NtrBC form a network to control the C/N balance in P. aeruginosa.
      Possible molecular mechanisms of these two regulatory elements in the control of
      arginine and histidine operons used as the model systems are discussed.

PMID- 17545290
TI  - Role of staphylococcal phage and SaPI integrase in intra- and interspecies SaPI
      transfer.
AB  - SaPIbov2 is a member of the SaPI family of staphylococcal pathogenicity islands
      and is very closely related to SaPIbov1. Typically, certain temperate phages can
      induce excision and replication of one or more of these islands and can package
      them into special small phage-like particles commensurate with their genome sizes
      (referred to as the excision-replication-packaging [ERP] cycle). We have studied
      the phage-SaPI interaction in some depth using SaPIbov2, with special reference
      to the role of its integrase. We demonstrate here that SaPIbov2 can be induced to
      replicate by different staphylococcal phages. After replication, SaPIbov2 is
      efficiently encapsidated and transferred to recipient organisms, including
      different non-Staphylococcus aureus staphylococci, where it integrates at a SaPI
      specific attachment site, att(C), by means of a self-coded integrase (Int).
      Phages that cannot induce the SaPIbov2 ERP cycle can transfer the island by recA
      dependent classical generalized transduction and can also transfer it by a novel
      mechanism that requires the expression of SaPIbov2 int in the recipient but not
      in the donor. It is suggested that this mechanism involves the encapsidation of
      standard transducing fragments containing the intact island followed by int
      mediated excision, circularization, and integration in the recipient.

PMID- 17545291
TI  - Cysteine scanning mutagenesis and topological mapping of the Escherichia coli
      twin-arginine translocase TatC Component.
AB  - The TatC protein is an essential component of the Escherichia coli twin-arginine
      (Tat) protein translocation pathway. It is a polytopic membrane protein that
      forms a complex with TatB, together acting as the receptor for Tat substrates. In
      this study we have constructed 57 individual cysteine substitutions throughout
      the protein. Each of the substitutions resulted in a TatC protein that was
      competent to support Tat-dependent protein translocation. Accessibility studies
      with membrane-permeant and -impermeant thiol-reactive reagents demonstrated that
      TatC has six transmembrane helices, rather than the four suggested by a previous
      study (K. Gouffi, C.-L. Santini, and L.-F. Wu, FEBS Lett. 525:65-70, 2002).
      Disulfide cross-linking experiments with TatC proteins containing single cysteine
      residues showed that each transmembrane domain of TatC was able to interact with
      the same domain from a neighboring TatC protein. Surprisingly, only three of
      these cysteine variants retained the ability to cross-link at low temperatures.
      These results are consistent with the likelihood that most of the disulfide cross
      links are between TatC proteins in separate TatBC complexes, suggesting that TatC
      is located on the periphery of the complex.

PMID- 17545292
TI  - pH of the cytoplasm and periplasm of Escherichia coli: rapid measurement by green
      fluorescent protein fluorimetry.
AB  - Cytoplasmic pH and periplasmic pH of Escherichia coli cells in suspension were
      observed with 4-s time resolution using fluorimetry of TorA-green fluorescent
      protein mutant 3* (TorA-GFPmut3*) and TetR-yellow fluorescent protein.
      Fluorescence intensity was correlated with pH using cell suspensions containing
      20 mM benzoate, which equalizes the cytoplasmic pH with the external pH. When the
      external pH was lowered from pH 7.5 to 5.5, the cytoplasmic pH fell within 10 to
      20 s to pH 5.6 to 6.5. Rapid recovery occurred until about 30 s after HCl
      addition and was followed by slower recovery over the next 5 min. As a control,
      KCl addition had no effect on fluorescence. In the presence of 5 to 10 mM acetate
      or benzoate, recovery from external acidification was diminished. Addition of
      benzoate at pH 7.0 resulted in cytoplasmic acidification with only slow recovery.
      Periplasmic pH was observed using TorA-GFPmut3* exported to the periplasm through
      the Tat system. The periplasmic location of the fusion protein was confirmed by
      the observation that osmotic shock greatly decreased the periplasmic fluorescence
      signal by loss of the protein but had no effect on the fluorescence of the
      cytoplasmic protein. Based on GFPmut3* fluorescence, the pH of the periplasm
      equaled the external pH under all conditions tested, including rapid acid shift.
      Benzoate addition had no effect on periplasmic pH. The cytoplasmic pH of E. coli
      was measured with 4-s time resolution using a method that can be applied to any
      strain construct, and the periplasmic pH was measured directly for the first
      time.

PMID- 17545294
TI  - Peri-operative second molar tube failure during orthognathic surgery: two case
      reports.
AB  - With improvements in bonding techniques, bracket base design and bond strengths,
      molar tubes are becoming more popular in orthodontics. Molar tubes make an
      attractive alternative to conventional banding due to a reduction in clinical
      bonding time and ease of placement on partially erupted teeth. The use of molar
      tubes negates the need for orthodontic separation and subsequent cementation of
      bands, and offers improved periodontal health. Their use on terminal molars,
      however, should be limited to non-orthognathic cases. This paper presents two
      cases of peri-operative second molar tube failure during orthognathic surgery.
      They are presented in the hope that it will highlight the importance of banding
      the distal terminal molar in orthognathic cases to prevent loss of molar tubes
      and peri-operative contamination of the surgical wound site.

PMID- 17545295
TI  - Mini-screw implants (temporary anchorage devices): orthodontic and pre-prosthetic
      applications.
AB  - Mini-screw implants, often referred to as temporary anchorage devices (TADs),
      have become an accepted component of orthodontic treatment. The comparatively
      simple technique for the placement of these mini-screws is described with
      emphasis on the importance of correct site selection as well as an understanding
      of the possible complications that may arise. The application and description of
      appliances incorporating mini-screws are described with the aid of typodont
      models and clinical examples. While the technique is of primary relevance to
      orthodontists, the use of mini-screws as an aid for pre-prosthodontic tooth
      movement is also of relevance to prosthodontists. From the examples described in
      this paper, extrapolations can be made by individual clinicians to situations
      relevant to their particular treatment plans. Examples of appliances used in
      conjunction with mini-screws are described; however, depending on the
      requirements of individual malocclusions, these designs may be modified.

PMID- 17545296
TI  - Choosing a pre-adjusted orthodontic appliance prescription for anterior teeth.
AB  - A common orthodontic task is to correct anterior tooth position using brackets
      whose torque, tip and in-out are pre-adjusted. Bracket prescription greatly
      influences final aesthetics and function. Pre-adjusted orthodontic brackets have
      in-built prescriptions of torque, tip and in-out which are optimized for average
      cases. Refinement of tooth position can be achieved by archwire adjustment or
      archwire auxiliaries. Modifications to bracket position such as inversion can
      also help achieve individual tooth movements. Planning bracket position must be
      considered at the outset of treatment to achieve the maximum benefit. A number of
      clinical scenarios will be discussed including: a Class II division 1
      malocclusion with lateral incisors palatally displaced, and another case with
      absent lateral incisors for space closure. Also, Class III malocclusions with
      consideration given to: canine angulation; a palatally displaced canine requiring
      labial movement; absent upper central incisors (space closure), and finally, a
      Class III case where incisor inclination requires consideration. By using a
      typodont to illustrate some of the points, this article aims to (1) show how
      three pre-adjusted orthodontic bracket systems (Andrews, Roth and MBT) vary
      significantly in their ability to influence tooth position and appearance; (2)
      inform clinicians how modified bracket position can influence tooth position.

PMID- 17545297
TI  - Skeletal anchorage systems in orthodontics: absolute anchorage. A dream or
      reality?
AB  - This article examines the concept of orthodontic anchorage and focuses on ways
      skeletally derived anchorage is gained. A brief history of the different skeletal
      anchorage systems to date is given. The article gives an emphasis on the use of
      one particular skeletal anchorage technique--the micro-implant--to assist with
      orthodontic anchorage and active tooth movement. Advantages and disadvantages of
      this new technique are discussed. An illustration of the use of micro-implants is
      given with reference to a case where they have been used in a novel manner to
      provide distal movement of maxillary molars.

PMID- 17545299
TI  - Elective orthognathic treatment decision making: a survey of patient reasons and
      experiences.
AB  - OBJECTIVE: Few studies have explored decisions about orthognathic treatment (OGT)
      from the patient's perspective. This study describes the factors associated with
      the patient's decision to have or not have orthognathic treatment, and assesses
      whether the process can be considered to be informed decision making. DESIGN: A
      cross-sectional survey employing both interview and questionnaire methods,
      conducted in four OGT services in Yorkshire. SAMPLE: Participants were patients
      aged over 16 years, either making an OGT decision over a 6-month period or had
      made their treatment choice 18-42 months prior to the study start date in 2003.
      MEASURES: Questionnaires assessed patient demographics, dental history and
      psychopathology (anxiety, satisfaction with self, body satisfaction, facial
      appearance); interviews explored patients' reasons for, and experiences of,
      orthognathic treatment. RESULTS: Of 138 patients approached, 61 participated
      (mean age 25 years, 66% female). Psychopathology scores were within the normal
      range. The thematic content analysis of interview transcripts found: reasons
      given for having OGT were to improve the 'bite', as well as gaining a more normal
      facial appearance; most patients reported the service information was
      satisfactory, but about half made negative comments, with some reporting staff
      communications made them feel worse; knowledge of OGT risks and benefits was
      poor; patients had strong emotions about their facial appearance and the
      orthognathic treatment they received, which did not seem to be addressed by
      current practice. CONCLUSIONS: Some OGT patients do not appear to be making
      informed decisions about their treatment. They seem to have unmet needs in
      relation to support for their decision making, and managing the emotional effects
      of undergoing and adjusting to treatment. The implications for information
      provision, assessment and support during treatment are discussed.

PMID- 17545300
TI  - Bonded versus banded first molar attachments: a randomized controlled clinical
      trial.
AB  - OBJECTIVE: To compare the clinical failure rates of bonded first molar tubes with
      those of cemented bands during fixed appliance therapy. DESIGN: Prospective
      randomized controlled clinical trial. SETTING: Two UK hospital orthodontic
      clinics, February 2001-December 2004. PARTICIPANTS: Hospital waiting list
      patients needing fixed appliances (n = 110). METHOD: Patients were randomly
      allocated to two groups. Experimental group patients (n = 55) received single
      first molar tubes (n = 181) bonded with a no-mix chemically cured composite (Rely
      A-Bond) after a 30-second etch. Control group patients (n = 55) were treated with
      bands (n = 186) cemented with Intact glass ionomer cement (GIC). First-time
      failures were recorded together with the time of failure. All patients were
      followed to the end or discontinuation of treatment. RESULTS: First-time
      failures: bands = 18.8%; bonds = 33.7 %. Bonded tubes were more likely to fail
      [RR 2.4; 95% CI (1.4, 4.1)] compared with bands. Experimental group patients also
      had more bracket failures (P = 0.009), when analysed at patient level.
      CONCLUSION: First molar tubes bonded with Rely-A-Bond composite showed a
      significantly higher first-time failure rate than bands cemented with Intact GIC.

PMID- 17545301
TI  - Current products and practice. How to create and manage a regional orthognathic
      database.
AB  - This is a report on the use of a regional database of patients undergoing
      orthognathic treatment in the South West of England. The benefits and
      difficulties of using a regional database are discussed.

PMID- 17545302
TI  - Uncoupling of the VEGF-endothelial nitric oxide axis in diabetic nephropathy: an
      explanation for the paradoxical effects of VEGF in renal disease.
AB  - In many forms of experimental kidney diseases, renal VEGF is low, and
      administering VEGF can be shown to be protective. A paradox occurs in diabetes,
      in which renal VEGF levels are high and a deleterious effect of VEGF on kidney
      disease has been shown. We have hypothesized that endothelial dysfunction induced
      by hyperglycemia or other factors may underlie the pathogenic mechanisms of a
      high VEGF state. VEGF normally stimulates endothelial nitric oxide (NO) release
      and acts in concert with elevated NO levels as a trophic factor for vascular
      endothelium. The increased NO derived from the endothelial cell acts as an
      inhibitory factor that prevents excess endothelial cell proliferation, vascular
      smooth muscle cell proliferation, and macrophage infiltration. In the setting
      where NO bioavailability is reduced in diabetes, high levels of VEGF lead to
      excessive endothelial cell proliferation, stimulation of macrophage chemotaxis,
      and vascular smooth muscle cell activation. Consistent with this hypothesis is
      our recent observation that diabetes induced in endothelial NO-deficient mice
      results in clinical and histological features identical to human diabetic
      nephropathy. The discovery of the key role for impaired endothelial NO
      bioavailability in the stimulation of VEGF and VEGF-dependent disease may provide
      key insights into not only the pathogenesis of diabetic nephropathy but also the
      utility and hazard of administering VEGF as a treatment for kidney disease.

PMID- 17545303
TI  - Energetic cost of synthesizing proteins in Antarctic limpet, Nacella concinna
      (Strebel, 1908), is not temperature dependent.
AB  - The energetic cost of protein synthesis is thought to account for a significant
      proportion of total metabolism. However, attempts to estimate the energetic cost
      of synthesizing proteins have resulted in surprisingly variable results,
      particularly for the small number of polar organisms studied, where cost
      estimates vary by two orders of magnitude. Much of this variability is probably
      the result of differing methodologies and experimental designs. Here we have used
      two different, carefully validated methods to measure the costs of protein
      synthesis in Antarctic limpets. One method, which utilized a specific protein
      synthesis inhibitor, was used to measure the cost of protein synthesis at two
      temperatures to test the hypothesis that the cost of protein synthesis varies
      with temperature. The cost of protein synthesis measured using the inhibitor
      cycloheximide was 13.95 +/- 0.77 micromol O2/mg protein, while correlation of
      absolute protein synthesis with oxygen consumption suggested the cost of protein
      synthesis was 19.58 micromol O2/mg protein. Water temperature did not alter the
      cost of protein synthesis in Nacella concinna (Student's t-test, P = 0.849, t =
      0.19, df = 12). In a meta-analysis of literature values for the cost of protein
      synthesis there was no significant effect of temperature, but there was a
      significant relationship between the concentration of cycloheximide used to
      inhibit protein synthesis and the measured cost.

PMID- 17545304
TI  - Tagging SNP haplotype analysis of the secretory PLA2-V gene, PLA2G5, shows strong
      association with LDL and oxLDL levels, suggesting functional distinction from
      sPLA2-IIA: results from the UDACS study.
AB  - Animal and human studies suggest that both secretory PLA2 (sPLA2)-V and sPLA2-IIA
      (encoded, respectively, by the neighbouring PLA2G5 and PLA2G2A genes) contribute
      to atherogenesis. Elevated plasma sPLA2-IIA predicts coronary heart disease (CHD)
      risk, but no mass assay for sPLA2-V is available. We previously reported that
      tagging single nucleotide polymorphism (tSNP) haplotypes of PLA2G2A are strongly
      associated with sPLA2-IIA mass, but not lipid levels. Here, we use tSNPs of the
      sPLA2-V gene to investigate the association of PLA2G5 with CHD risk markers.
      Seven PLA2G5 tSNPs genotypes, explaining >92% of the locus genetic variability,
      were determined in 519 patients with Type II diabetes (in whom PLA2G2A tSNP data
      was available), and defined seven common haplotypes (frequencies >5%). PLA2G5 and
      PLA2G2A tSNPs showed linkage disequilibrium (LD). Compared to the common PLA2G5
      haplotype, H1 (frequency 34.9%), haplotypes H2-7 were associated with overall
      higher plasma LDL (P < 0.00004) and total cholesterol (P < 0.00003) levels yet
      lower oxLDL/LDL (P = 0.006) and sPLA2-IIA mass (P = 0.04), probably reflecting LD
      with PLA2G2A. Intronic tSNP (rs11573248), unlikely itself to be functional,
      distinguished H1 from LDL-raising haplotypes and may mark a functional site. In
      conclusion, PLA2G5 tSNP haplotypes demonstrate an association with total and LDL
      cholesterol and oxLDL/LDL, not seen with PLA2G2A, thus confirming distinct
      functional roles for these two sPLA2s.

PMID- 17545305
TI  - Collaboration between the ClpB AAA+ remodeling protein and the DnaK chaperone
      system.
AB  - ClpB and Hsp104, members of the AAA+ superfamily of proteins, protect cells from
      the devastating effects of protein inactivation and aggregation that arise after
      extreme heat stress. They exist as a hexameric ring and contain two nucleotide
      binding sites per monomer. ClpB and Hsp104 are able to dissolve protein
      aggregates in conjunction with the DnaK/Hsp70 chaperone system, although the
      roles of the individual chaperones in disaggregation are not well understood. In
      the absence of the DnaK/Hsp70 system, ClpB and Hsp104 alone are able to perform
      protein remodeling when their ATPase activity is asymmetrically slowed either by
      providing a mixture of ATP and ATP gamma S, a nonphysiological and slowly
      hydrolyzed ATP analog, or by inactivating one of the two nucleotide-binding
      domains by mutation. To gain insight into the roles of ClpB and the DnaK system
      in protein remodeling, we tested whether there was a further stimulation by the
      DnaK chaperone system under conditions that elicited remodeling activity by ClpB
      alone. Our results demonstrate that ClpB and the DnaK system act synergistically
      to remodel proteins and dissolve aggregates. The results further show that ATP is
      required and that both nucleotide-binding sites of ClpB must be able to hydrolyze
      ATP to permit functional collaboration between ClpB and the DnaK system.

PMID- 17545306
TI  - Long-range structural effects of a Charcot-Marie-Tooth disease-causing mutation
      in human glycyl-tRNA synthetase.
AB  - Functional expansion of specific tRNA synthetases in higher organisms is well
      documented. These additional functions may explain why dominant mutations in
      glycyl-tRNA synthetase (GlyRS) and tyrosyl-tRNA synthetase cause Charcot-Marie
      Tooth (CMT) disease, the most common heritable disease of the peripheral nervous
      system. At least 10 disease-causing mutant alleles of GlyRS have been annotated.
      These mutations scatter broadly across the primary sequence and have no apparent
      unifying connection. Here we report the structure of wild type and a CMT-causing
      mutant (G526R) of homodimeric human GlyRS. The mutation is at the site for
      synthesis of glycyl-adenylate, but the rest of the two structures are closely
      similar. Significantly, the mutant form diffracts to a higher resolution and has
      a greater dimer interface. The extra dimer interactions are located approximately
      30 A away from the G526R mutation. Direct experiments confirm the tighter dimer
      interaction of the G526R protein. The results suggest the possible importance of
      subtle, long-range structural effects of CMT-causing mutations at the dimer
      interface. From analysis of a third crystal, an appended motif, found in higher
      eukaryote GlyRSs, seems not to have a role in these long-range effects.

PMID- 17545308
TI  - Influence of base stacking on excited-state behavior of polyadenine in water,
      based on time-dependent density functional calculations.
AB  - A thorough study of the excited-state properties of the stacked dimers and
      trimers of 9-methyladenine in B-DNA conformation has been performed in aqueous
      solution by using time-dependent density functional calculations and the solvent
      polarizable continuum model, and results were compared with experimental results
      on polyadenine oligomers. The effect of base stacking on the absorption and
      emission spectra is fully reproduced by our calculations. Although light
      absorption leads to a state (S(B)) delocalized over several nucleobases, excited
      state geometry optimization indicates that S(B) subsequently evolves into a state
      in which the excitation is localized on a single base. Analysis of the excited
      state potential energy surfaces shows that S(B) can easily decay into the lowest
      energy excited state, S(CT), which is a dark excimer produced by intermonomer
      charge transfer between two stacked bases. The subpicosecond features of the time
      resolved experiments are interpreted in terms of ultrafast decay from S(B). After
      localization, two easy, radiationless decay channels are indeed open for S(B):
      (i) ground-state recovery, according to the same mechanisms proposed for isolated
      adenine and/or (ii) decay to S(CT). Our calculations suggest that the slowest
      part of the excited-state dynamics detected experimentally involves the S(CT)
      state.

PMID- 17545307
TI  - Dopaminergic modulation of short-term synaptic plasticity at striatal inhibitory
      synapses.
AB  - Circuit properties, such as the selection of motor synergies, have been posited
      as relevant tasks for the recurrent inhibitory synapses between spiny projection
      neurons of the neostriatum, a nucleus of the basal ganglia participating in
      procedural learning and voluntary motor control. Here we show how the
      dopaminergic system regulates short-term plasticity (STP) in these synapses. STP
      is thought to endow neuronal circuits with computational powers such as gain
      control, filtering, and the emergence of transitory net states. But little is
      known about STP regulation. Employing unitary and population synaptic recordings,
      we observed that activation of dopamine receptors can modulate STP between spiny
      neurons. A D(1)-class agonist enhances, whereas a D(2)-class agonist decreases,
      short-term depression most probably by synaptic redistribution. Presynaptic
      receptors appear to be responsible for this modulation. In contrast, STP between
      fast-spiking interneurons and spiny projection neurons is largely unregulated
      despite expressing presynaptic receptors. Thus, the present experiments provide
      an explanation for dopamine actions at the circuit level: the control of STP
      between lateral connections of output neurons and the reorganization of the
      balance between different forms of inhibitory transmission. Theoretically, D(1)
      receptors would promote a sensitive, responsive state for temporal precision
      (dynamic component), whereas D(2) receptors would sense background activity
      (static component).

PMID- 17545309
TI  - Mechanical limits of viral capsids.
AB  - We studied the elastic properties and mechanical stability of viral capsids under
      external force-loading with computer simulations. Our approach allows the
      implementation of specific geometries corresponding to specific phages, such as
      phi29 and cowpea chlorotic mottle virus. We demonstrate how, in a combined
      numerical and experimental approach, the elastic parameters can be determined
      with high precision. The experimentally observed bimodality of elastic spring
      constants is shown to be of geometrical origin, namely the presence of
      pentavalent units in the viral shell. We define a criterion for capsid breakage
      that explains well the experimentally observed rupture. From our numerics we find
      a crossover from gamma(2/3) to gamma(1/2) for the dependence of the rupture force
      on the Foppl-von Karman number, gamma. For filled capsids, high internal
      pressures lead to a stronger destabilization for viruses with buckled ground
      states versus viruses with unbuckled ground states. Finally, we show how our
      numerically calculated energy maps can be used to extract information about the
      strength of protein-protein interactions from rupture experiments.

PMID- 17545310
TI  - 2-[4-[(5,6-diphenylpyrazin-2-yl)(isopropyl)amino]butoxy]-N
      (methylsulfonyl)acetamide (NS-304), an orally available and long-acting
      prostacyclin receptor agonist prodrug.
AB  - Prostacyclin (PGI(2)) and its analogs are useful for the treatment of various
      vascular disorders, but their half-lives are too short for widespread clinical
      application. To overcome this drawback, we have synthesized a novel
      diphenylpyrazine derivative, 2-[4-[(5,6-diphenylpyrazin-2
      yl)(isopropyl)amino]butoxy]-N-(methylsulfonyl)acetamide (NS-304), a prodrug of
      the active form [4-[(5,6-diphenylpyrazin-2-yl)(isopropyl)amino]butoxy]acetic acid
      (MRE-269). NS-304 is an orally available and potent agonist for the PGI(2)
      receptor (IP receptor). The inhibition constant (K(i)) of MRE-269 for the human
      IP receptor was 20 nM; in contrast, the K(i) values for other prostanoid
      receptors were >2.6 microM. MRE-269 was therefore a highly selective agonist for
      the IP receptor. The plasma concentrations of MRE-269 remained near peak levels
      for more than 8 h after oral administration of NS-304 to rats and dogs, and NS
      304 increased femoral skin blood flow in rats in a long-lasting manner without
      affecting the hemodynamics. These findings indicate that NS-304 acts as a long
      acting IP receptor agonist in vivo. The continuous vasodilation evoked by NS-304
      was not attenuated by repeated treatment, indicating that NS-304 is unlikely to
      cause severe desensitization of the IP receptor in rats. Moreover, a microdose
      pharmacokinetic study in which NS-304 was orally administered to healthy male
      volunteers showed conversion of NS-304 to MRE-269 and a long plasma elimination
      half-life for MRE-269 (7.9 h). In conclusion, NS-304 is an orally available and
      long-acting IP receptor agonist prodrug, and its active form, MRE-269, is highly
      selective for the IP receptor. Therefore, NS-304 is a promising drug candidate
      for various vascular diseases, especially pulmonary arterial hypertension and
      arteriosclerosis obliterans.

PMID- 17545311
TI  - Opposing control of cannabinoid receptor stimulation on amyloid-beta-induced
      reactive gliosis: in vitro and in vivo evidence.
AB  - Beside cytotoxic mechanisms impacting on neurons, amyloid beta (A beta)-induced
      astroglial activation is operative in Alzheimer's disease brain, suggesting that
      persistent inflammatory response may have a role in the illness and that positive
      results may be achieved by curbing the astroglial reaction. Because the role of
      the endocannabinoid system could represent a promising field of research, the
      present study conducted in vitro and in vivo experiments to assess this system.
      C6 rat astroglioma cells were challenged with 1 microg/ml A beta 1-42 in the
      presence or absence of selective agonists and antagonists of cannabinoid (CB)1
      and CB2 receptors. Furthermore, rats were inoculated into the frontal cortex with
      30 ng of A beta 1-42 and were i.p. administered with 5 mg/kg of the same
      substances. Immunohistochemical and biochemical findings revealed that selective
      agonism at CB1 and antagonism at CB2 receptors was able to blunt A beta-induced
      reactive astrogliosis with subsequent overexpression of glial fibrillary acidic
      protein and S100B protein. Moreover, A beta provoked down-regulation of CB1
      receptors together with a reduction of anandamide concentration, whereas CB2
      receptors were up-regulated and 2-arachidonoyl glycerol concentration was
      increased. Finally, to our knowledge, the current study is the first showing that
      interactions at cannabinoid receptors result in a dual regulation of A beta
      induced reactive astrogliosis. The data support the assumption that compounds
      able to selectively block CB2 receptors may have therapeutic potential in
      controlling A beta-related pathology, due to their beneficial effects devoid of
      psychotropic consequences.

PMID- 17545312
TI  - Modulation of brainstem opiate analgesia in the rat by sigma 1 receptors: a
      microinjection study.
AB  - sigma(1) Receptors have been implicated in the modulation of opioid analgesia. In
      the current study, we examined the role of sigma(1) systems in the periaqueductal
      gray (PAG), the rostroventral medulla (RVM), and the locus coeruleus (LC) of the
      rat, regions previously shown to be sensitive to morphine. Morphine was a potent
      analgesic in all three regions. Coadministration of the sigma(1) agonist (+)
      pentazocine diminished the analgesic actions of morphine in all three regions,
      although the PAG was far less sensitive than the other two regions. Blockade of
      the sigma(1) receptors with haloperidol in the RVM markedly enhanced the
      analgesic actions of coadministered morphine, implying a tonic activity of the
      sigma(1) system in this region. This effect was mimicked by down-regulation of
      RVM sigma(1) receptors using an antisense approach. However, no tonic sigma(1)
      activity was observed in either the LC or the PAG. The RVM also was important in
      modulating analgesia elicited from morphine microinjected into the PAG. The
      analgesic actions of morphine given into the PAG could be attenuated by (+)
      pentazocine placed into the RVM, whereas haloperidol in the RVM enhanced PAG
      morphine analgesia. These studies illustrate the pharmacological importance of
      sigma(1) receptors in the brainstem modulation of opioid analgesia.

PMID- 17545313
TI  - Endocannabinoid enhancement protects against kainic acid-induced seizures and
      associated brain damage.
AB  - Endocannabinoids are released in response to pathogenic insults, and inhibitors
      of endocannabinoid inactivation enhance such on-demand responses that promote
      cellular protection. Here, AM374 (palmitylsulfonyl fluoride), an irreversible
      inhibitor of fatty acid amide hydrolase (FAAH), was injected i.p. into rats to
      test for endocannabinoid enhancement. AM374 caused a prolonged elevation of
      anandamide levels in several brain regions, including the hippocampus, and
      resulted in rapid activation of the extracellular signal regulated-kinase/mitogen
      activated protein kinase pathway that has been linked to survival. To evaluate
      the neuroprotective nature of the FAAH inhibitor, we tested AM374 in a seizure
      model involving rats insulted with kainic acid (KA). AM374 was injected
      immediately after KA administration, and seizure scores were significantly
      reduced throughout a 4-h observation period. The KA-induced seizures were
      associated with calpain-mediated cytoskeletal breakdown, reductions in synaptic
      markers, and loss of CA1 hippocampal neurons. FAAH inhibition protected against
      the excitotoxic damage and neuronal loss assessed 48 h postinsult. AM374 also
      preserved pre- and postsynaptic markers to levels comparable with those found in
      noninsulted animals, and the synaptic marker preservation strongly correlated
      with reduced seizure scores. With regard to behavioral deficits in the
      excitotoxic rats, AM374 produced nearly complete functional protection,
      significantly improving balance and coordination across different behavioral
      paradigms. These data indicate that AM374 crosses the blood-brain barrier,
      enhances endocannabinoid responses in key neuronal circuitries, and protects the
      brain against excitotoxic damage.

PMID- 17545314
TI  - Trichoderma atroviride PHR1, a fungal photolyase responsible for DNA repair,
      autoregulates its own photoinduction.
AB  - The photolyases, DNA repair enzymes that use visible and long-wavelength UV light
      to repair cyclobutane pyrimidine dimers (CPDs) created by short-wavelength UV,
      belong to the larger photolyase-cryptochrome gene family. Cryptochromes (UVA-blue
      light photoreceptors) lack repair activity, and sensory and regulatory roles have
      been defined for them in plants and animals. Evolutionary considerations indicate
      that cryptochromes diverged from CPD photolyases before the emergence of
      eukaryotes. In prokaryotes and lower eukaryotes, some photolyases might have
      photosensory functions. phr1 codes for a class I CPD photolyase in Trichoderma
      atroviride. phr1 is rapidly induced by blue and UVA light, and its photoinduction
      requires functional blue light regulator (BLR) proteins, which are White Collar
      homologs in Trichoderma. Here we show that deletion of phr1 abolished
      photoreactivation of UVC (200 to 280 nm)-inhibited spores and thus that PHR1 is
      the main component of the photorepair system. The 2-kb 5' upstream region of
      phr1, with putative light-regulated elements, confers blue light regulation on a
      reporter gene. To assess phr1 photosensory function, fluence response curves of
      this light-regulated promoter were tested in null mutant (Deltaphr1) strains.
      Photoinduction of the phr1 promoter in Deltaphr1 strains was >5-fold more
      sensitive to light than that in the wild type, whereas in PHR1-overexpressing
      lines the sensitivity to light increased about 2-fold. Our data suggest that PHR1
      may regulate its expression in a light-dependent manner, perhaps through negative
      modulation of the BLR proteins. This is the first evidence for a regulatory role
      of photolyase, a role usually attributed to cryptochromes.

PMID- 17545315
TI  - Mutual dependence of Candida albicans Est1p and Est3p in telomerase assembly and
      activation.
AB  - Telomerase is an RNA-protein complex responsible for extending one strand of the
      telomere terminal repeats. Analysis of the telomerase complex in budding yeasts
      has revealed the presence of one catalytic protein subunit (Est2p/TERT) and at
      least two noncatalytic components (Est1p and Est3p). The TERT subunit is
      essential for telomerase catalysis, while the functions of Est1p and Est3p have
      not been precisely elucidated. In an earlier study, we showed that telomerase
      derived from a Candida est1-null mutant is defective in primer utilization in
      vitro; it exhibits reduced initiation and processivity on primers that terminate
      in two regions of the telomere repeat. Here we show that telomerase derived from
      a Candida est3-null mutant has nearly identical defects in primer utilization and
      processivity. Further analysis revealed an unexpected mutual dependence of Est1p
      and Est3p in their assembly into the full telomerase complex, which accounts for
      the similarity between the mutant enzymes. We also developed an affinity
      isolation and an in vitro reconstitution protocol for the telomerase complex that
      will facilitate future mechanistic studies.

PMID- 17545317
TI  - Engineering of Saccharomyces cerevisiae for efficient anaerobic alcoholic
      fermentation of L-arabinose.
AB  - For cost-effective and efficient ethanol production from lignocellulosic
      fractions of plant biomass, the conversion of not only major constituents, such
      as glucose and xylose, but also less predominant sugars, such as l-arabinose, is
      required. Wild-type strains of Saccharomyces cerevisiae, the organism used in
      industrial ethanol production, cannot ferment xylose and arabinose. Although
      metabolic and evolutionary engineering has enabled the efficient alcoholic
      fermentation of xylose under anaerobic conditions, the conversion of l-arabinose
      into ethanol by engineered S. cerevisiae strains has previously been demonstrated
      only under oxygen-limited conditions. This study reports the first case of fast
      and efficient anaerobic alcoholic fermentation of l-arabinose by an engineered S.
      cerevisiae strain. This fermentation was achieved by combining the expression of
      the structural genes for the l-arabinose utilization pathway of Lactobacillus
      plantarum, the overexpression of the S. cerevisiae genes encoding the enzymes of
      the nonoxidative pentose phosphate pathway, and extensive evolutionary
      engineering. The resulting S. cerevisiae strain exhibited high rates of arabinose
      consumption (0.70 g h(-1) g [dry weight](-1)) and ethanol production (0.29 g h(
      1) g [dry weight](-1)) and a high ethanol yield (0.43 g g(-1)) during anaerobic
      growth on l-arabinose as the sole carbon source. In addition, efficient ethanol
      production from sugar mixtures containing glucose and arabinose, which is crucial
      for application in industrial ethanol production, was achieved.

PMID- 17545316
TI  - Identification and characterization of CPS1 as a hyaluronic acid synthase
      contributing to the pathogenesis of Cryptococcus neoformans infection.
AB  - Cryptococcus neoformans is a pathogenic yeast that often causes devastating
      meningoencephalitis in immunocompromised individuals. We have previously
      identified the C. neoformans CPS1 gene, which is required for a capsular layer on
      the outer cell wall. In this report, we investigate the function of the CPS1 gene
      and its pathogenesis. We demonstrated that treatment of yeast with either 4
      methylumbelliferone or hyaluronidase resulted in a reduction of the level of C.
      neoformans binding to human brain microvascular endothelial cells (HBMEC). Yeast
      extracellular structures were also altered accordingly in hyaluronidase-treated
      cells. Furthermore, observation of yeast strains with different hyaluronic acid
      contents showed that the ability to bind to HBMEC is proportional to the
      hyaluronic acid content. A killing assay with Caenorhabditis elegans demonstrated
      that the CPS1 wild-type strain is more virulent than the cps1Delta strain. When
      CPS1 is expressed in Saccharomyces cerevisiae and Escherichia coli, hyaluronic
      acid can be detected in the cells. Additionally, we determined by fluorophore
      assisted carbohydrate electrophoretic analysis that hyaluronic acid is a
      component of the C. neoformans capsule. The size of hyaluronic acid molecules is
      evaluated by gel filtration and transmission electron microscopy studies.
      Together, our results support that C. neoformans CPS1 encodes hyaluronic acid
      synthase and that its product, hyaluronic acid, plays a role as an adhesion
      molecule during the association of endothelial cells with yeast.

PMID- 17545318
TI  - Genetic diversity of rhizobia associated with Acacia longifolia in two stages of
      invasion of coastal sand dunes.
AB  - We examined the genetic diversity of root nodule bacteria associated with the
      Australian legume Acacia longifolia in two stages of invasion of a coastal sand
      dune system. All isolates belonged to the genus Bradyrhizobium. A higher
      diversity was found in the long-established trees. The results suggest the
      introduction of exotic bradyrhizobia with the plant.

PMID- 17545319
TI  - Quantitative analysis of population heterogeneity of the adaptive salt stress
      response and growth capacity of Bacillus cereus ATCC 14579.
AB  - Bacterial populations can display heterogeneity with respect to both the adaptive
      stress response and growth capacity of individual cells. The growth dynamics of
      Bacillus cereus ATCC 14579 during mild and severe salt stress exposure were
      investigated for the population as a whole in liquid culture. To quantitatively
      assess the population heterogeneity of the stress response and growth capacity at
      a single-cell level, a direct imaging method was applied to monitor cells from
      the initial inoculum to the microcolony stage. Highly porous Anopore strips were
      used as a support for the culturing and imaging of microcolonies at different
      time points. The growth kinetics of cells grown in liquid culture were comparable
      to those of microcolonies grown upon Anopore strips, even in the presence of mild
      and severe salt stress. Exposure to mild salt stress resulted in growth that was
      characterized by a remarkably low variability of microcolony sizes, and the
      distributions of the log(10)-transformed microcolony areas could be fitted by the
      normal distribution. Under severe salt stress conditions, the microcolony sizes
      were highly heterogeneous, and this was apparently caused by the presence of both
      a nongrowing and growing population. After discriminating these two
      subpopulations, it was shown that the variability of microcolony sizes of the
      growing population was comparable to that of non-salt-stressed and mildly salt
      stressed populations. Quantification of population heterogeneity during stress
      exposure may contribute to an optimized application of preservation factors for
      controlling growth of spoilage and pathogenic bacteria to ensure the quality and
      safety of minimally processed foods.

PMID- 17545320
TI  - Agrobacterium tumefaciens fur has important physiological roles in iron and
      manganese homeostasis, the oxidative stress response, and full virulence.
AB  - In Agrobacterium tumefaciens, the balance between acquiring enough iron and
      avoiding iron-induced toxicity is regulated in part by Fur (ferric uptake
      regulator). A fur mutant was constructed to address the physiological role of the
      regulator. Atypically, the mutant did not show alterations in the levels of
      siderophore biosynthesis and the expression of iron transport genes. However, the
      fur mutant was more sensitive than the wild type to an iron chelator, 2,2'
      dipyridyl, and was also more resistant to an iron-activated antibiotic,
      streptonigrin, suggesting that Fur has a role in regulating iron concentrations.
      A. tumefaciens sitA, the periplasmic binding protein of a putative ABC-type iron
      and manganese transport system (sitABCD), was strongly repressed by Mn(2+) and,
      to a lesser extent, by Fe(2+), and this regulation was Fur dependent. Moreover,
      the fur mutant was more sensitive to manganese than the wild type. This was
      consistent with the fact that the fur mutant showed constitutive up-expression of
      the manganese uptake sit operon. Fur(At) showed a regulatory role under iron
      limiting conditions. Furthermore, Fur has a role in determining oxidative
      resistance levels. The fur mutant was hypersensitive to hydrogen peroxide and had
      reduced catalase activity. The virulence assay showed that the fur mutant had a
      reduced ability to cause tumors on tobacco leaves compared to wild-type NTL4.

PMID- 17545321
TI  - Germination of Bacillus cereus spores is induced by germinants from
      differentiated Caco-2 Cells, a human cell line mimicking the epithelial cells of
      the small intestine.
AB  - Spores of 11 enterotoxigenic strains of Bacillus cereus isolated from foods and
      humans adhered with similar efficiencies to Caco-2 cells, whereas subsequent
      germination triggering was observed with only 8 of these strains. Notably, Hep-2
      cells did not trigger germination, while spores of all strains displayed similar
      germination efficiencies in brain heart infusion broth.

PMID- 17545323
TI  - Isolation and characterization of a novel haloacid permease from Burkholderia
      cepacia MBA4.
AB  - Burkholderia cepacia MBA4 is a bacterium that can utilize 2-haloacids as carbon
      and energy sources for growth. It has been proposed that dehalogenase-associated
      permease mediates the uptake of haloacid. In this paper, we report the first
      cloning and characterization of such a haloacid permease. The structural gene,
      designated deh4p, was found 353 bases downstream of the dehalogenase gene deh4a.
      Quantitative analysis of the expression of deh4p showed that it was induced by
      monochloroacetate (MCA), to a level similar to the MCA-induced level of deh4a.
      The nucleotide sequence of deh4p was determined, and an open reading frame of
      1,656 bp encoding a putative peptide of 552 amino acids was identified. Deh4p has
      a putative molecular weight of 59,414 and an isoelectric point of 9.88. Deh4p has
      the signatures of sugar transport proteins and integral membrane proteins of the
      major facilitator superfamily. Uptake of [(14)C]MCA into the cell was Deh4p
      dependent. Deh4p has apparent K(m)s of 5.5 and 8.9 muM and V(max)s of 9.1 and
      23.1 nmol mg(-1) min(-1) for acetate and MCA, respectively. A mutant with a
      transposon-inactivated haloacid operon failed to grow on MCA even when deh4a was
      provided in trans.

PMID- 17545322
TI  - Phylogenetic and metabolic diversity of Planctomycetes from anaerobic, sulfide-
      and sulfur-rich Zodletone Spring, Oklahoma.
AB  - We investigated the phylogenetic diversity and metabolic capabilities of members
      of the phylum Planctomycetes in the anaerobic, sulfide-saturated sediments of a
      mesophilic spring (Zodletone Spring) in southwestern Oklahoma. Culture
      independent analyses of 16S rRNA gene sequences generated using Planctomycetes
      biased primer pairs suggested that an extremely diverse community of
      Planctomycetes is present at the spring. Although sequences that are
      phylogenetically affiliated with cultured heterotrophic Planctomycetes were
      identified, the majority of the sequences belonged to several globally
      distributed, as-yet-uncultured Planctomycetes lineages. Using complex organic
      media (aqueous extracts of the spring sediments and rumen fluid), we isolated two
      novel strains that belonged to the Pirellula-Rhodopirellula-Blastopirellula clade
      within the Planctomycetes. The two strains had identical 16S rRNA gene sequences,
      and their closest relatives were isolates from Kiel Fjord (Germany), Keauhou
      Beach (HI), a marine aquarium, and tissues of marine organisms (Aplysina sp.
      sponges and postlarvae of the giant tiger prawn Penaeus monodon). The closest
      recognized cultured relative of strain Zi62 was Blastopirellula marina (93.9%
      sequence similarity). Detailed characterization of strain Zi62 revealed its
      ability to reduce elemental sulfur to sulfide under anaerobic conditions, as well
      as its ability to produce acids from sugars; both characteristics may potentially
      allow strain Zi62 to survive and grow in the anaerobic, sulfide- and sulfur-rich
      environment at the spring source. Overall, this work indicates that anaerobic
      metabolic abilities are widely distributed among all major Planctomycetes
      lineages and suggests carbohydrate fermentation and sulfur reduction as possible
      mechanisms employed by heterotrophic Planctomycetes for growth and survival under
      anaerobic conditions.

PMID- 17545324
TI  - Monitoring and source tracking of tetracycline resistance genes in lagoons and
      groundwater adjacent to swine production facilities over a 3-year period.
AB  - To monitor the dissemination of resistance genes into the environment, we
      determined the occurrence of tetracycline resistance (Tc(r)) genes in groundwater
      underlying two swine confinement operations. Monitoring well networks (16 wells
      at site A and 6 wells at site C) were established around the lagoons at each
      facility. Groundwater (n = 124) and lagoon (n = 12) samples were collected from
      the two sites at six sampling times from 2000 through 2003. Total DNA was
      extracted, and PCR was used to detect seven Tc(r) genes [tet(M), tet(O), tet(Q),
      tet(W), tet(C), tet(H), and tet(Z)]. The concentration of Tc(r) genes was
      quantified by real-time quantitative PCR. To confirm the Tc(r) gene source in
      groundwater, comparative analysis of tet(W) gene sequences was performed on
      groundwater and lagoon samples. All seven Tc(r) genes were continually detected
      in groundwater during the 3-year monitoring period at both sites. At site A,
      elevated detection frequency and concentration of Tc(r) genes were observed in
      the wells located down-gradient of the lagoon. Comparative analysis of tet(W)
      sequences revealed that the impacted groundwater contained gene sequences almost
      identical (99.8% identity) to those in the lagoon, but these genes were not found
      in background libraries. Novel sequence clusters and unique indigenous resistance
      gene pools were also found in the groundwater. Thus, antibiotic resistance genes
      in groundwater are affected by swine manure, but they are also part of the
      indigenous gene pool.

PMID- 17545325
TI  - NCgl2620 encodes a class II polyphosphate kinase in Corynebacterium glutamicum.
AB  - Corynebacterium glutamicum is able to accumulate up to 600 mM cytosolic
      phosphorus in the form of polyphosphate (poly P). Granular poly P (volutin) can
      make up to 37% of the internal cell volume. This bacterium lacks the classic
      enzyme of poly P synthesis, class I polyphosphate kinase (PPK1), but it possesses
      two genes, ppk2A (corresponds to NCgl0880) and ppk2B (corresponds to NCgl2620),
      for putative class II (PPK2) PPKs. Deletion of ppk2B decreased PPK activity and
      cellular poly P content, while overexpression of ppk2B increased both PPK
      activity and cellular poly P content. Neither deletion nor overexpression of
      ppk2A changed specific activity of PPK or cellular poly P content significantly.
      Purified PPK2B of C. glutamicum is active as a homotetramer and formed poly P
      with an average chain length of about 125, as determined with (31)P nuclear
      magnetic resonance. The catalytic efficiency of C. glutamicum PPK2B was higher in
      the poly P-forming direction than for nucleoside triphosphate formation from poly
      P. The ppk2B deletion mutant, which accumulated very little poly P and grew as C.
      glutamicum wild type under phosphate-sufficient conditions, showed a growth
      defect under phosphate-limiting conditions.

PMID- 17545326
TI  - Formate as an auxiliary substrate for glucose-limited cultivation of Penicillium
      chrysogenum: impact on penicillin G production and biomass yield.
AB  - Production of beta-lactams by the filamentous fungus Penicillium chrysogenum
      requires a substantial input of ATP. During glucose-limited growth, this ATP is
      derived from glucose dissimilation, which reduces the product yield on glucose.
      The present study has investigated whether penicillin G yields on glucose can be
      enhanced by cofeeding of an auxiliary substrate that acts as an energy source but
      not as a carbon substrate. As a model system, a high-producing industrial strain
      of P. chrysogenum was grown in chemostat cultures on mixed substrates containing
      different molar ratios of formate and glucose. Up to a formate-to-glucose ratio
      of 4.5 mol.mol(-1), an increasing rate of formate oxidation via a cytosolic
      NAD(+)-dependent formate dehydrogenase increasingly replaced the dissimilatory
      flow of glucose. This resulted in increased biomass yields on glucose. Since at
      these formate-to-glucose ratios the specific penicillin G production rate
      remained constant, the volumetric productivity increased. Metabolic modeling
      studies indicated that formate transport in P. chrysogenum does not require an
      input of free energy. At formate-to-glucose ratios above 4.5 mol.mol(-1), the
      residual formate concentrations in the cultures increased, probably due to
      kinetic constraints in the formate-oxidizing system. The accumulation of formate
      coincided with a loss of the coupling between formate oxidation and the
      production of biomass and penicillin G. These results demonstrate that, in
      principle, mixed-substrate feeding can be used to increase the yield on a carbon
      source of assimilatory products such as beta-lactams.

PMID- 17545327
TI  - Control of Mycosphaerella graminicola on wheat seedlings by medical drugs known
      to modulate the activity of ATP-binding cassette transporters.
AB  - Medical drugs known to modulate the activity of human ATP-binding cassette (ABC)
      transporter proteins (modulators) were tested for the ability to potentiate the
      activity of the azole fungicide cyproconazole against in vitro growth of
      Mycosphaerella graminicola and to control disease development due to this
      pathogen on wheat seedlings. In vitro modulation of cyproconazole activity could
      be demonstrated in paper disk bioassays. Some of the active modulators
      (amitriptyline, flavanone, and phenothiazines) increased the accumulation of
      cyproconazole in M. graminicola, suggesting that they reversed cyproconazole
      efflux. However, synergism between cyproconazole and modulators against M.
      graminicola on wheat seedlings could not be shown. Despite their low in vitro
      toxicity to M. graminicola, some modulators (amitriptyline, loperamide, and
      promazine) did show significant intrinsic disease control activity in preventive
      and curative foliar spray tests with wheat seedlings. The results suggest that
      these compounds have indirect disease control activity based on modulation of
      fungal ABC transporters essential for virulence and constitute a new class of
      disease control agents.

PMID- 17545328
TI  - Effect of nutrient starvation on the cellular composition and metabolic capacity
      of Saccharomyces cerevisiae.
AB  - This investigation addresses the following question: what are the important
      factors for maintenance of a high catabolic capacity under various starvation
      conditions? Saccharomyces cerevisiae was cultured in aerobic batch cultures, and
      during the diauxic shift cells were transferred and subjected to 24 h of
      starvation. The following conditions were used: carbon starvation, nitrogen
      starvation in the presence of glucose or ethanol, and both carbon starvation and
      nitrogen starvation. During the starvation period changes in biomass composition
      (including protein, carbohydrate, lipid, and nucleic acid contents), metabolic
      activity, sugar transport kinetics, and the levels of selected enzymes were
      recorded. Subsequent to the starvation period the remaining catabolic capacity
      was measured by addition of 50 mM glucose. The results showed that the glucose
      transport capacity is a key factor for maintenance of high metabolic capacity in
      many, but not all, cases. The results for cells starved of carbon, carbon and
      nitrogen, or nitrogen in the presence of glucose all indicated that the metabolic
      capacity was indeed controlled by the glucose transport ability, perhaps with
      some influence of hexokinase, phosphofructokinase, aldolase, and enolase levels.
      However, it was also demonstrated that there was no such correlation when
      nitrogen starvation occurred in the presence of ethanol instead of glucose.

PMID- 17545329
TI  - Toward automated analysis of biofilm architecture: bias caused by extraneous
      confocal laser scanning microscopy images.
AB  - An increasing number of studies utilize confocal laser scanning microscopy (CLSM)
      for in situ visualization of biofilms and rely on the use of image analysis
      programs to extract quantitative descriptors of architecture. Recently, designed
      programs have begun incorporating procedures to automatically determine threshold
      values for three-dimensional CLSM image stacks. We have found that the automated
      threshold calculation is biased when a stack contains images lacking pixels of
      biological significance. Consequently, we have created the novel program Auto
      PHLIP-ML to resolve this bias by iteratively excluding extraneous images based on
      their area coverage of biomass. A procedure was developed to identify the optimal
      percent area coverage value used for extraneous image removal (PACVEIR). The
      optimal PACVEIR was defined to occur when the standard deviation of mean
      thickness, determined from replicate image stacks, was at a maximum, because it
      more accurately reflected inherent structural variation. Ten monoculture biofilms
      of either Ralstonia eutropha JMP228n::gfp or Acinetobacter sp. strain BD413 were
      tested to verify the routine. All biofilms exhibited an optimal PACVEIR between 0
      and 1%. Prior to the exclusion of extraneous images, JMP228n::gfp appeared to
      develop more homogeneous biofilms than BD413. However, after the removal of
      extraneous images, JMP228n::gfp biofilms were found to form more heterogeneous
      biofilms. Similarly, JMP228n::gfp biofilms grown on glass surfaces vis-a-vis
      polyethylene membranes produced significantly different architectures after
      extraneous images had been removed but not when such images were included in
      threshold calculations. This study shows that the failure to remove extraneous
      images skewed a seemingly objective analysis of biofilm architecture and
      significantly altered statistically derived conclusions.

PMID- 17545330
TI  - Inhaled corticosteroids for asthma.

PMID- 17545331
TI  - Apparent life-threatening events (ALTEs) and the role of home monitors.

PMID- 17545332
TI  - Sudden infant death syndrome.

PMID- 17545333
TI  - Pediatric head injury.

PMID- 17545334
TI  - Index of suspicion.

PMID- 17545335
TI  - Visual diagnosis: an 8-month-old infant who has an erupting rash.

PMID- 17545337
TI  - Complementary, holistic, and integrative medicine: butterbur.

PMID- 17545339
TI  - Misconnecting for health: (lack of) advice for professionals on the safe use of
      mobile phone technology.

PMID- 17545340
TI  - Rates and types of events reported to established incident reporting systems in
      two US hospitals.
AB  - BACKGROUND: US hospitals have had voluntary incident reporting systems for many
      years, but the effectiveness of these systems is unknown. To facilitate
      substantial improvements in patient safety, the systems should capture incidents
      reflecting the spectrum of adverse events that are known to occur in hospitals.
      OBJECTIVE: To characterise the incidents from established voluntary hospital
      reporting systems. DESIGN: Observational study examining about 1000 reports of
      hospitalised patients at each of two hospitals. PATIENTS AND SETTING: 16 575
      randomly selected patients from an academic and a community hospital in the US in
      2001. MAIN OUTCOME MEASURES: Rates of incidents reported per hospitalised patient
      and characteristics of reported incidents. RESULTS: 9% of patients had at least
      one reported incident; 17 incidents were reported per 1000 patient-days in
      hospital. Nurses filed 89% of reports, physicians 1.9% and other providers 8.9%.
      The most common types were medication incidents (29%), falls (14%), operative
      incidents (15%) and miscellaneous incidents (16%); 59% seemed preventable and
      preventability was not clear for 32%. Among the potentially preventable
      incidents, 43% involved nurses, 16% physicians and 19% other types of providers.
      Qualitative examination of reports indicated that very few involved prescribing
      errors or high-risk procedures. CONCLUSIONS: Hospital reporting systems receive
      many reports, but capture a spectrum of incidents that differs from the adverse
      events known to occur in hospitals, thereby substantially underdetecting
      physician incidents, particularly those involving operations, high-risk
      procedures and prescribing errors. Increasing the reporting of physician
      incidents will be essential to enhance the effectiveness of hospital reporting
      systems; therefore, barriers to reporting such incidents must be minimised.

PMID- 17545341
TI  - Evaluation of an intervention aimed at improving voluntary incident reporting in
      hospitals.
AB  - OBJECTIVES: To assess the effectiveness of an intervention package comprising
      intense education, a range of reporting options, changes in report management and
      enhanced feedback, in order to improve incident-reporting rates and change the
      types of incidents reported. DESIGN, SETTING AND PARTICIPANTS: Non-equivalent
      group controlled clinical trial involving medical and nursing staff working in 10
      intervention and 10 control units in four major cities and two regional hospitals
      in South Australia. MAIN OUTCOME MEASURES: Comparison of reporting rates by type
      of unit, profession, location of hospital, type of incident reported and
      reporting mechanism between baseline and study periods in control and
      intervention units. RESULTS: The intervention resulted in significant improvement
      in reporting in inpatient areas (additional 60.3 reports/10,000 occupied bed days
      (OBDs); 95% CI 23.8 to 96.8, p<0.001) and in emergency departments (EDs)
      (additional 39.5 reports/10,000 ED attendances; 95% CI 17.0 to 62.0, p<0.001).
      More reports were generated (a) by doctors in EDs (additional 9.5 reports/10,000
      ED attendances; 95% CI 2.2 to 16.8, p = 0.001); (b) by nurses in inpatient areas
      (additional 59.0 reports/10,000 OBDs; 95% CI 23.9 to 94.1, p<0.001) and (c)
      anonymously (additional 20.2 reports/10,000 OBDs and ED attendances combined; 95%
      CI 12.6 to 27.8, p<0.001). Compared with control units, the study resulted in
      more documentation, clinical management and aggression-related incidents in
      intervention units. In intervention units, more reports were submitted on one
      page forms than via the call centre (1005 vs 264 reports, respectively).
      CONCLUSIONS: A greater variety and number of incidents were reported by the
      intervention units during the study, with improved reporting by doctors from a
      low baseline. However, there was considerable heterogeneity between reporting
      rates in different types of units.

PMID- 17545342
TI  - Why poor quality of ethnicity data should not preclude its use for identifying
      disparities in health and healthcare.
AB  - BACKGROUND: Data of quality are needed to identify ethnic disparities in health
      and healthcare and to meet the challenges in governance of race relations. Yet
      concerns over completeness, accuracy and timeliness have been long-standing and
      inhibitive with respect to the analytical use of the data. AIMS: To identify
      incompleteness of ethnicity data across routine health and healthcare datasets
      and to investigate the utility of analytical strategies for using data that is of
      suboptimal quality. METHODS: An analysis by government office regions of
      ethnicity data incompleteness in routine datasets and a comprehensive review and
      evaluation of the literature on appropriate analytical strategies to address the
      use of such data. RESULTS: There is only limited availability of ethnically coded
      routine datasets on health and healthcare, with substantial variability in valid
      ethnic coding: although a few have high levels of completeness, the majority are
      poor (notably hospital episode statistics, drug treatment data and non-medical
      workforce). In addition, there is also a more than twofold regional difference in
      quality. Organisational factors seem to be the main contributor to the
      differentials, and these are amenable-yet, in practice, difficult-to change. This
      article discusses the strengths and limitations of a variety of analytical
      strategies for using data of suboptimal quality and explores how they may answer
      important unresolved questions in relation to ethnic inequalities. CONCLUSIONS:
      Only by using the data, even when of suboptimal quality, and remaining close to
      it can healthcare organisations drive up quality.

PMID- 17545343
TI  - Safety of telephone triage in general practitioner cooperatives: do triage nurses
      correctly estimate urgency?
AB  - BACKGROUND: In recent years, there has been a growth in the use of triage nurses
      to decrease general practitioner (GP) workloads and increase the efficiency of
      telephone triage. The actual safety of decisions made by triage nurses has not
      yet been assessed. OBJECTIVES: To investigate whether triage nurses accurately
      estimate the urgency level of health complaints when using the national telephone
      guidelines, and to examine the relationship between the performance of triage
      nurses and their education and training. METHOD: A cross-sectional, multicentre,
      observational study employing five mystery (simulated) patients who telephoned
      triage nurses in four GP cooperatives. The mystery patients played standardised
      roles. Each role had one of four urgency levels as determined by experts. The
      triage nurses called were asked to estimate the level of urgency after the
      contact. This level of urgency was compared with a gold standard. RESULTS: Triage
      nurses estimated the level of urgency of 69% of the 352 contacts correctly and
      underestimated the level of urgency of 19% of the contacts. The sensitivity and
      specificity of the urgency estimates provided by the triage nurses were found to
      be 0.76 and 0.95, respectively. The positive and negative predictive values of
      the urgency estimates were 0.83 and 0.93, respectively. A significant correlation
      was found between correct estimation of urgency and specific training on the use
      of the guidelines. The educational background (primary or secondary care) of the
      nurses had no significant relationship with the rate of underestimation.
      CONCLUSION: Telephone triage by triage nurses is efficient but possibly not safe,
      with potentially severe consequences for the patient. An educational programme
      for triage nurses is recommended. Also, a direct second safety check of all cases
      by a specially trained GP telephone doctor is advisable.

PMID- 17545344
TI  - Have Nursing Home Compare quality measure scores changed over time in response to
      competition?
AB  - BACKGROUND: Currently, the Centers for Medicare and Medicaid Services report on
      15 Quality Measures (QMs) on the Nursing Home Compare (NHC) website. It is
      assumed that nursing homes are able to make improvements on these QMs, and in
      doing so they will attract more residents. In this investigation, we examine
      changes in QM scores, and whether competition and/or excess demand have
      influenced these change scores over a period of 1 year. METHODS: Data come from
      NHC and the On-line Survey Certification And Recording (OSCAR) system. QM change
      scores are calculated using values from January 2003 to January 2004. A series of
      regression analyses are used to examine the association of competition and excess
      demand on QM scores. RESULTS: Eight QMs show an average decrease in scores (ie,
      better quality) and six QMs show an average increase in scores (ie, worse
      quality). However, for 13 of the 14 QMs these average changes averaged less than
      1%. The regression analyses show an association between higher competition and
      improving QM scores and an association between lower occupancy and improving QM
      scores. CONCLUSION: As would be predicted based on the market-driven mechanism
      underlying quality improvements using report cards, we show that it is in the
      most competitive markets and those with the lowest average occupancy rates that
      improvements in the QM scores are more likely.

PMID- 17545345
TI  - Monitoring the rate of re-exploration for excessive bleeding after cardiac
      surgery in adults.
AB  - BACKGROUND: The monitoring of adverse events in clinical care can be an important
      part of quality assurance. There is little evidence on the monitoring of re
      exploration after cardiac surgery. OBJECTIVE: To apply statistical monitoring
      techniques to the rate of re-exploration for excessive bleeding in adult patients
      undergoing cardiac surgery procedures using cardiopulmonary bypass at Geelong
      Hospital, Victoria, Australia, between 1997 and 2003. METHODS: Shewhart charts,
      moving average plots and cumulative sum (CUSUM) charts were used to demonstrate
      changes in the rate of re-exploration over time. RESULTS: A CUSUM chart was used
      retrospectively at a time of perceived deteriorating clinical outcomes in
      patients of the cardiac surgery service. At this time, an intervention aimed at
      reducing the re-exploration rate was performed, and subsequent CUSUM charts
      indicated an improvement in this rate. The CUSUM chart has become an important
      part of the quality feedback of clinical care outcomes within the Anaesthesia &
      Pain Management unit of Geelong Hospital. CONCLUSION: Statistical monitoring
      techniques for quality assurance can identify important changes in clinical
      performance, and their adoption by clinicians is recommended.

PMID- 17545346
TI  - What is the role of quality circles in strategies to optimise antibiotic
      prescribing? A pragmatic cluster-randomised controlled trial in primary care.
AB  - OBJECTIVE: To evaluate the effect on antibiotic prescribing of an intervention in
      existing local quality circles promoting an evidence-based guideline for acute
      rhinosinusitis. DESIGN: A pragmatic cluster-randomised controlled trial comparing
      standard dissemination of the guideline by mail with an additional strategy using
      quality circles. SETTING: General practice in Flanders, Belgium. PARTICIPANTS:
      General practitioners (GPs) in 18 local quality circles were randomly allocated
      to two study arms. All GPs received the guideline by mail. GPs in the nine
      quality circles allocated to the intervention arm received an additional group
      intervention, which consisted of one self-led meeting using material introduced
      to the group moderator by a member of the research team. MAIN OUTCOME MEASURES:
      Adherence to the guideline was measured as differences in the proportion of
      antibiotic prescriptions, including the choice of antibiotic, between the two
      study arms after the intervention period. GPs registered their encounters with
      patients presenting with signs and symptoms of acute rhinosinusitis in a booklet
      designed for the study. RESULTS: A total of 75 doctors (29% of GPs in the
      participating quality circles) registered 408 consultations. In the intervention
      group, 56.9% of patients received an antibiotic compared with 58.3% in the
      control group. First-choice antibiotics were issued in 34.5% of antibiotic
      prescriptions in the intervention group compared with 29.4% in the control group.
      After adjusting for patient and GP characteristics, the ORadj for antibiotics
      prescribed in the intervention arm compared with the control arm was 0.63 (95% CI
      0.29 to 1.37). There was no effect on the choice of antibiotic (ORadj 1.07, 95%
      CI 0.34 to 3.37). CONCLUSION: A single intervention in quality circles of GPs
      integrated in the group's normal working procedure did not have a significant
      effect on the quality of antibiotic prescribing. More attention to the context
      and structure of primary care practice, and insight into the process of self
      reflective learning may provide clues to optimise the effectiveness of quality
      circles.

PMID- 17545347
TI  - Quality control of surgical and interventional procedures: a review of the CUSUM.
AB  - BACKGROUND: The report of the CUSUM across surgical and interventional procedures
      has spawned a fair confusion in the literature. AIM: To assess the use of the
      CUSUM and to clarify its utilisation in the perspective of future studies. Nature
      of the study: Retrospective review. METHODS: A systematic literature search of
      Medline was carried out. From each article, data regarding the design of the
      study, the specialty, the performance criterion, the unit under control, the
      methodology and the model of the CUSUM used, the use of a graph, the use of a
      test and the type of test applied were retrieved. RESULTS: 31 studies were found
      relevant. The design was mainly retrospective for the analysis of the learning
      curve. The main performance criteria under control were morbidity, mortality and
      success of the procedure. A graph was plotted in all studies as a CUSUM plot or
      as cumulative sums of non-negative values. A test was used in 17 studies.
      Mislabelling of the plot and the test, and misuse of control limits were the most
      commonly reported mistakes. CONCLUSION: The CUSUM tool is not yet properly
      reported in the surgical literature. Therefore, reporting of the CUSUM should be
      clarified and standardised before its use widens.

PMID- 17545348
TI  - Risk assessment in diabetes management: how do general practitioners estimate
      risks due to diabetes?
AB  - OBJECTIVES: To evaluate the ability of general practitioners (GPs) in Germany to
      estimate the risk of patients with diabetes developing complications. METHODS: An
      interview study using a structured questionnaire to estimate risks of four case
      vignettes having diabetes-specific complications within the next 10 years, risk
      reduction and life expectancy potential. A representative random sample of 584
      GPs has been drawn, of which 150 could be interviewed. We compared GPs' estimates
      among each other (intraclass correlation coefficient (ICC) and Cohen's
      (multirater-) kappa) and with risks for long-term complications generated by the
      multifactor disease model "Mellibase", which is a knowledge-based support system
      for medical decision management. RESULTS: The risk estimates by GPs varied widely
      (ICC 0.21 95% CI (0.13 to 0.36)). The average level of potential risk reduction
      was between 47% and 70%. Compared with Mellibase values, on average, the GPs
      overestimated the risk threefold. Mean estimates of potential prolongation of
      life expectancy were close to 10 years for each patient, whereas the Mellibase
      calculations ranged from 3 to 10 years. CONCLUSIONS: Overestimation could lead to
      unnecessary care and waste of resources.

PMID- 17545349
TI  - Patients use an internet technology to report when things go wrong.
AB  - BACKGROUND: As patients directly experience harm from adverse events,
      investigators have proposed patient-report to complement professional reporting
      of adverse events. OBJECTIVE: To investigate how an automated health assessment
      system can be used to identify adverse events. DESIGN AND SETTING: Internet
      survey responses from April 2003 to April 2005 involving communities and clinical
      practices across the USA. PATIENTS: 44,860 adults aged 19-69 years. OUTCOME:
      Patient perceptions of adverse events experienced during the previous year.
      Independent legal review was also used to estimate how many patient-reports were
      serious enough to be potentially compensable. RESULTS: Although patient reports
      of possible adverse events was low (1.4%), the percentage of adverse events was
      eight times higher for patients with the greatest burden of illness than for
      those with the least (3.4% vs 0.4%). Two expert malpractice attorneys agreed that
      9% of the adverse events seemed to be serious. CONCLUSIONS: PATIENTS will use
      internet technology to report their perceptions of health-related adverse events.
      Some of the patient-reported events reported will be serious.

PMID- 17545350
TI  - A patient decision aid to support shared decision-making on anti-thrombotic
      treatment of patients with atrial fibrillation: randomised controlled trial.
AB  - OBJECTIVE: To determine the efficacy of a computerised decision aid in patients
      with atrial fibrillation making decisions on whether to take warfarin or aspirin
      therapy. DESIGN: Two-armed open exploratory randomised controlled trial. SETTING:
      Two research clinics deriving participants from general practices in Northeast
      England. PARTICIPANTS: 109 patients with atrial fibrillation aged over 60.
      INTERVENTIONS: Computerised decision aid applied in shared decision-making clinic
      compared to evidence-based paper guidelines applied as direct advice. MAIN
      OUTCOME MEASURES: Primary outcome measure was the decision conflict scale.
      Secondary outcome measures included anxiety, knowledge, decision-making
      preference, treatment decision, use of primary and secondary care services and
      health outcomes. RESULTS: Decision conflict was lower in the computerised
      decision aid group immediately after the clinic; mean difference -0.18 (95% CI 
      0.34 to -0.01). Participants in this group not already on warfarin were much less
      likely to start warfarin than those in the guidelines arm (4/16, 25% compared to
      the guidelines group 15/16, 93.8%, RR 0.27, 95% CI 0.11 to 0.63). CONCLUSIONS:
      Decision conflict was lower immediately following the use of a computerised
      decision aid in a shared decision-making consultation than immediately following
      direct doctor-led advice based on paper guidelines. Furthermore, participants in
      the computerised decision aid group were significantly much less likely to start
      warfarin than those in the guidelines arm. The results show that such an approach
      has a positive impact on decision conflict comparable to other studies of
      decision aids, but also reduces the uptake of a clinically effective treatment
      that may have important implications for health outcomes.

PMID- 17545351
TI  - Qualitative methods in a randomised controlled trial: the role of an integrated
      qualitative process evaluation in providing evidence to discontinue the
      intervention in one arm of a trial of a decision support tool.
AB  - OBJECTIVE: To understand participants' experiences and understandings of the
      interventions in the trial of a computerised decision support tool in patients
      with atrial fibrillation being considered for anti-coagulation treatment. DESIGN:
      Qualitative process evaluation carried out alongside the trial: non-participant
      observation and semistructured interviews. PARTICIPANTS: 30 participants aged >60
      years taking part in the trial of a computerised decision support tool. RESULTS:
      Qualitative evidence provided the rationale to undertake a decision to
      discontinue one arm of the trial on the basis that the intervention in that arm,
      a standard gamble values elicitation exercise was causing confusion and was
      unlikely to produce valid data on participant values. CONCLUSIONS: Qualitative
      methods used alongside a trial allow an understanding of the process and progress
      of a trial, and provide evidence to intervene in the trial if necessary,
      including evidence for the rationale to discontinue an intervention arm of the
      trial.

PMID- 17545352
TI  - Recommendations for promoting the engagement of older people in activities to
      prevent falls.
AB  - OBJECTIVE: To develop recommendations for promoting uptake of and adherence to
      falls-prevention interventions among older people. DESIGN: The recommendations
      were initially developed from literature review, clinical experience of the core
      group members, and substantial qualitative and quantitative studies of older
      people's views. They were refined through a consultation process with members of
      the falls-prevention community, drawing on Delphi survey and nominal group
      techniques. Transparency was enhanced by recording and reporting aspects of the
      iterative consultation process such as the degree of consensus and critical
      comments on drafts of the recommendations. SETTING: The recommendations were
      developed and refined at three meetings of the core group, and through internet
      based consultation and two meetings involving members of the wider falls
      prevention community. PARTICIPANTS: The authors developed the recommendations
      incorporating the feedback from the researchers and practitioners responding to a
      broad-based internet consultation and consulted in the meetings. RESULTS: A high
      degree of consensus was achieved. Recommendations addressed the need for public
      education, ensuring that interventions were compatible with a positive identity,
      tailoring interventions to the specific situation and values of the individual,
      and using validated methods to maintain longer-term adherence. CONCLUSION: These
      recommendations represent a consensus based on current knowledge and evidence,
      but the evidence base from which these recommendations were developed was
      limited, and not always specific to prevention of falls. To increase the
      effectiveness of falls-prevention interventions, further research is needed to
      identify the features of falls-prevention programmes that will encourage older
      people's engagement in them.

PMID- 17545353
TI  - How do surgeons make intraoperative decisions?
AB  - Surgeons' intraoperative decision making is a key element of clinical practice,
      yet has received scant attention in the surgical literature. In recent years,
      serial changes in the configuration of surgical training in the UK have reduced
      the time spent by trainees in the operating theatre. The opportunity to replace
      this lost experience with active teaching of decision making is important, but
      there seem to have been very few studies that have directly examined the
      cognitive skills underlying surgical decision making during operations. From the
      available evidence in surgery, and drawing from research in other safety-critical
      occupations, four decision-making strategies that surgeons may use are discussed:
      intuitive (recognition-primed), rule based, option comparison and creative.
      Surgeons' decision-making processes should be studied to provide a better
      evidence base for the training of cognitive skills for the intraoperative
      environment.

PMID- 17545354
TI  - Current preoperative marking practice by UK ophthalmologists.

PMID- 17545355
TI  - Violent entertainment pitched to adolescents: an analysis of PG-13 films.
AB  - OBJECTIVE: The purpose of this study was to evaluate the violence content of the
      top-grossing PG-13 films of 1999 and 2000 to determine what percentage of it had
      potential for negative effects on young viewers and what percentage of it had
      potential for prosocial or beneficial effects. METHODS: A large, multidimensional
      analytic instrument was designed for systematic coding of each act of violence
      and its contextualization by features that have been shown either to enhance or
      to protect against harmful effects that are associated with violent media
      exposure: perpetrators and victims of violence, motivation for violence, presence
      of weapons, degree of realism, and consequences of violence. Descriptive
      statistics by genre were performed for each film. An ordinal logistic regression
      model was used to examine the association between the seriousness of violence and
      weapons, motive, and genre. RESULTS: In the sample of 77 PG-13 films, a total of
      2251 violent actions were observed with roughly half (47%) of lethal magnitude. A
      total of 118 acts contained justified violence that were initiated by major
      characters and were extremely serious, and approximately two thirds of the films
      (49 [64%]) were rated PG-13 for reasons other than violence. CONCLUSIONS:
      Violence permeated nearly 90% of the films in our study. Although only a small
      subset of this content contained violence that was associated with negative
      effects, only 1 film contained violence that was associated with protective or
      beneficial effects.

PMID- 17545356
TI  - A multicenter, randomized, double-blind, placebo-controlled trial to evaluate the
      metabolic and respiratory effects of growth hormone in children with cystic
      fibrosis.
AB  - OBJECTIVE: Positive effects of growth hormone therapy on growth, nutritional
      status, and lung function have been observed in patients with cystic fibrosis,
      but the current evidence is based on unblinded studies that involved a small
      number of patients. This trial was designed as a multicenter, randomized, placebo
      controlled, double-blind study to assess the efficacy and safety of 2 dosages of
      growth hormone in cystic fibrosis. METHODS: Sixty-three dystrophic patients with
      cystic fibrosis were randomly assigned for 24 weeks to 1 of 3 treatment arms:
      growth hormone dosage of 0.11 IU/kg body weight per day, growth hormone dosage of
      0.21 IU/kg body weight per day, or placebo. The 24-week double-blind period was
      followed by an open treatment period of 24 weeks. The primary outcome measure was
      the change in forced expiratory volume in 1 second in percentage predicted from
      baseline. Secondary outcome measures were changes in height, weight, and exercise
      tolerance. RESULTS: Height, growth velocity, and growth factors (insulin-like
      growth factor 1 and insulin-like growth factor-binding protein 3) increased
      significantly in both treatment groups, whereas weight gain did not differ
      between the growth hormone groups and placebo. A trend toward improvement in
      absolute forced vital capacity was observed in patients who received the higher
      growth hormone dosage, whereas forced expiratory volume in 1 second did not
      change significantly with growth hormone treatment. Maximal oxygen uptake during
      peak exercise increased significantly in treated patients. There were no
      significant differences in the frequency or severity of adverse effects or in the
      incidence of abnormalities in glucose metabolism. CONCLUSIONS: These data suggest
      that in the group investigated, growth hormone therapy was well tolerated and had
      positive metabolic effects but did not result in short-term improvement of lung
      function in patients with cystic fibrosis.

PMID- 17545357
TI  - A randomized, controlled trial of a removable brace versus casting in children
      with low-risk ankle fractures.
AB  - OBJECTIVES: Isolated distal fibular ankle fractures in children are very common
      and at very low risk for future complications. Nevertheless, standard therapy for
      these fractures still consists of casting, a practice that carries risks,
      inconveniences, and use of subspecialty health care resources. Therefore, the
      main objective of this study was to determine whether children who have these low
      risk ankle fractures that are treated with a removable ankle brace have at least
      as effective a recovery of physical function as those that are treated with a
      cast. METHODS: This was a noninferiority, randomized, single-blind trial in which
      children who were 5 to 18 years of age and treated in a pediatric emergency
      department for low-risk ankle fractures were randomly assigned to a removable
      ankle brace or a below-knee walking cast. The primary outcome at 4 weeks was
      physical function, measured by using the modified Activities Scale for Kids.
      Additional outcomes included patient preferences and costs. RESULTS: The mean
      activity score at 4 weeks was 91.3% in the brace group (n = 54), and this was
      significantly higher than the mean of 85.3% in the cast group (n = 50).
      Significantly more children who were treated with a brace had returned to
      baseline activities by 4 weeks compared with those who were casted (80.8% vs
      59.5%). Fifty-four percent of the casted children would have preferred the brace,
      but only 5.7% of children who received the brace would have preferred the cast.
      The cost-effectiveness acceptability curve was always >80%; therefore, the brace
      was cost-effective compared with the cast. CONCLUSIONS: The removable ankle brace
      is more effective than the cast with respect to recovery of physical function, is
      associated with a faster return to baseline activities, is superior with respect
      to patient preferences, and is also cost-effective.

PMID- 17545358
TI  - Birth weight, postnatal growth, and risk for high blood pressure at 7 years of
      age: results from the Collaborative Perinatal Project.
AB  - OBJECTIVE: A physiologic predisposition toward hypertension is theorized to
      result from the combination of intrauterine growth restriction followed by rapid
      catch-up growth. The objective of this study was to evaluate the effects of birth
      weight and weight gain during childhood on the risk for high blood pressure in
      childhood and to identify discrete periods of catch-up growth that put children
      with intrauterine growth restriction at increased risk for the development of
      high blood pressure later in life. METHODS: The US Collaborative Perinatal
      Project (1959-1974) studied 55,908 pregnancies in an observational cohort at 12
      medical centers in the United States and followed the offspring through 7 years
      of age. All white or black children who were born at term and completed the
      follow-up without kidney or heart disease were included in this posthoc analysis.
      z scores were calculated for weight at birth, 4 months, 1 year, 4 years, and 7
      years on the basis of study means and SD. Changes in z scores were calculated for
      each interval. RESULTS: Each 1-kg increase in birth weight increased the odds for
      high systolic blood pressure by 2.19 and high diastolic blood pressure by 1.82
      when race and change in weight z scores were also included in the regression
      model. An increase in weight z score of 1 SD above the previous weight z score
      increased the odds for high systolic blood pressure at 7 years by 1.65 (birth to
      4 months), 1.79 (4 months to 1 year), 1.71 (1-4 years), and 1.94 (4-7 years) in
      the full model. White race increased the odds for high systolic blood pressure by
      1.51. CONCLUSIONS: In this large biracial US cohort, infants who were small for
      gestational age were not at increased risk for high blood pressure at 7 years of
      age. However, children who crossed weight percentiles upward during early
      childhood did demonstrate an increased risk.

PMID- 17545359
TI  - Firearm ownership and storage patterns among families with children who receive
      well-child care in pediatric offices.
AB  - OBJECTIVE: In this study we examined firearm storage patterns and their
      associations in a diverse sample of families who attended pediatric practices
      from both rural and nonrural areas across the United States. METHODS: Parents who
      brought their children who were aged 2 to 11 years (N = 3745) to 96 Pediatric
      Research in Office Settings practices from 45 states, Canada, and Puerto Rico
      participated in an office-based survey before a well-child examination. The
      survey measured demographic variables; family history of guns in the home; and
      firearm types, storage behaviors, and ownership. RESULTS: Twenty-three percent of
      families reported firearm ownership. The majority (60%) of respondents reported
      making firearm storage decisions. Only one third of firearm owners reported safe
      firearm storage. Gun type owned was associated with storage habits, with long-gun
      owners storing their gun in places other than locked cabinets but with ammunition
      separate from guns and handgun users more likely to store guns loaded and to use
      gun locks. In a multivariate analysis, not being raised with a firearm was
      associated with safe storage behaviors. Families who had children aged 2 to 5
      years and owned long guns were more likely to store their guns safely than
      families with older children. CONCLUSIONS: Few families reported safe firearm
      storage. Storage patterns are most influenced by firearm type(s) owned, family
      socialization with guns, and the age of the child. Primary care providers need to
      understand better not only whether firearms are in the home but also which types
      are present and whether parents were raised in homes with guns.

PMID- 17545360
TI  - Heelys and street gliders injuries: a new type of pediatric injury.
AB  - OBJECTIVES: Our goals were to highlight an increasing trend in orthopedic
      injuries in children as a result of "heeling" or "street gliding," to describe
      injuries sustained by children using Heelys (HSL, Carrollton, TX) and Street
      Gliders (Glowgadgets Ltd, Bristol, United Kingdom), and to increase public
      awareness and prevent such injuries. PATIENTS AND METHODS: We prospectively
      recorded the data of all roller shoes injuries referred to our department during
      the summer school holiday. Using a data-collection sheet, we recorded demographic
      data, type of injury, mechanism and place of injury, heeling or street-gliding
      experience, use of safety equipment, methods of treatment, and intention to
      continue heeling or street gliding after recovery from injury. RESULTS: Over a 10
      week period, 67 children suffered orthopedic injuries while using Heelys or
      Street Gliders. There were 56 girls and 11 boys with a mean age of 9.6 years.
      Upper limbs were the most common location of injury. Distal radius fractures were
      the most prevalent, followed by supracondylar fractures, elbow dislocations, and
      hand fractures. The majority of children suffered the injury while heeling or
      street gliding outdoors. Interestingly, 20% of the injuries happened while trying
      Heelys or Street Gliders for the first time, and 36% of the injuries occurred
      while learning (using 1-5 times) how to use them. None of the children used any
      sort of protective gear at the time of the injury. The majority of the injured
      children expressed their intention to continue heeling or street gliding after
      complete recovery from their injury. CONCLUSIONS: Our study shows that the
      majority of children with injuries from heeling or street gliding are girls. We
      recommend close supervision of children using Heelys or Street Gliders during the
      steep learning curve and usage of protective gear at all times. These new types
      of injuries have a serious impact on child health and constitute a burden for the
      pediatric orthopedic service.

PMID- 17545361
TI  - Do skinfold measurements provide additional information to body mass index in the
      assessment of body fatness among children and adolescents?
AB  - OBJECTIVES: The purpose of this work was to validate the performance of age- and
      gender-specific BMI, triceps, and subscapular skinfold for the classification of
      excess of body fat in children and adolescents and to examine how much additional
      information these 2 skinfold measurements provide to BMI-for-age. METHODS: The
      receiver operating characteristic curve was used to characterize the sensitivity
      and specificity of these 3 indices in classifying excess body fat. Percentage of
      body fat was determined by dual-energy radiograph absorptiometry. Both > or =
      85th and > or = 95th percentile of percentage of body fat were used to define
      excess body fat. Data from the New York Pediatric Rosetta Body Composition
      Project were examined (n = 1196; aged 5-18 years). RESULTS: For children aged 5
      to 18 years, BMI-for-age, triceps skinfold-for-age, and subscapular skinfold-for
      age each performed equally well alone in the receiver operating characteristic
      curves in the identification of excess body fat defined by either the 85th or
      95th percentile of percentage of body fat by dual-energy radiograph
      absorptiometry. However, if BMI-for-age was already known and was > 95th
      percentile, the additional measurement of skinfolds did not significantly
      increase the sensitivity or specificity in the identification of excess body fat.
      CONCLUSIONS: In contrast to the recommendations of expert panels, skinfold
      measurements do not seem to provide additional information about excess body fat
      beyond BMI-for-age alone if the BMI-for-age is >95th percentile.

PMID- 17545362
TI  - Differences in severity-adjusted pediatric hospitalization rates are associated
      with race/ethnicity.
AB  - OBJECTIVE: Racial/ethnic disparities in health care delivery have been well
      described, but little is known about such disparities for children who seek
      emergency care. The objective of this study was to test the hypothesis that
      severity-adjusted emergency department pediatric admission rates are associated
      with race/ethnicity. METHODS: Secondary analyses were conducted of an established
      database of 16 emergency departments that participated in a national study to
      validate the Pediatric Risk of Admission II score, which is used to measure
      severity of illness. Patients were randomly selected by the coordinating center
      from daily emergency department visit logs. Crude and severity-adjusted admission
      rates were compared among the 3 most common races/ethnicities: white, black, and
      Hispanic. Adjusted admission rates were calculated by using the standardized
      admission ratio, which was calculated by dividing the observed admissions by the
      predicted admissions, when predicted was calculated from the Pediatric Risk of
      Admission II score. RESULTS: After exclusion of 3 sites that recorded
      race/ethnicity in <10% of patients, there were 13 sites with 8952 patients in the
      3 major race/ethnicity groups. Black and Hispanic patients were similar to each
      other and different from white patients; therefore, these 2 groups were combined
      for analyses. Both crude (8.2% vs 5.3%) and severity-adjusted (standardized
      admission ratio: 1.71 vs 1.1) admission rates were higher in white than in
      nonwhite patients. Standardized admission ratios were close to 1.0 in both
      race/ethnicity groups in the higher quintiles of illness severity. In contrast,
      white patients were admitted at 1.5 to 2 times the expected rate in the lowest 2
      quintiles of severity. CONCLUSIONS: There are differences in both crude and
      adjusted admission rates between white and black/Hispanic patients. The results
      are more consistent with high rates of discretionary admissions for white
      patients with low illness severity than with underadmitting severely ill black or
      Hispanic patients.

PMID- 17545363
TI  - Families' health-related social problems and missed referral opportunities.
AB  - OBJECTIVES: The objectives of this study were to characterize (1) families'
      cumulative burden of health-related social problems regarding access to health
      care, housing, food security, income security, and intimate partner violence; (2)
      families' experiences regarding screening and referral for social problems; and
      (3) parental acceptability of screening and referral. METHODS: We surveyed 205
      parents of children who were 0 to 6 years of age and attended 2 urban pediatric
      clinics for a well-child visit using a self-administered, computer-based
      questionnaire. The questionnaire included previously validated questions about
      health-related social problems and new questions about screening and referral in
      the past 12 months. RESULTS: A total of 205 (79%) of 260 eligible families
      participated. Eighty-two percent of families reported > or = 1 health-related
      social problem; 54% experienced problems in > or = 2 social domains. Families
      experienced similar types and frequencies of problems despite demographic
      differences between clinics. One third of families reported no screening in any
      domain in the previous 12 months. Of 205 families, 143 (70%) identified at least
      1 need for a referral; 101 (49%) expressed > or = 1 unmet referral need. Of
      families who reported receiving referrals, 115 referrals were received by 79
      families; of the referrals made, 63% (73 of 115) led to contact with the referral
      agency, and 82% (60 of 73) of the referral agencies were considered helpful. A
      computer-based system in a pediatrician's office for future screening and
      referral for health-related social problems was deemed acceptable by 92% of
      parents. CONCLUSIONS: Urban children and families reported a significant burden
      of health-related social problems yet infrequent pediatric screening or referral
      for these problems. Of families who reported receiving referrals, a majority
      contacted the recommended agencies and found them helpful. This study also
      demonstrates the feasibility of using a computer-based questionnaire to identify
      health-related social problems in a routine outpatient clinic setting.

PMID- 17545364
TI  - Visual function at 11 years of age in preterm-born children with and without
      fetal brain sparing.
AB  - OBJECTIVE: We have demonstrated earlier an accelerated maturation of the visual
      evoked potential in the first year of life in preterm infants with antenatal
      brain sparing. We have now assessed visual functioning at 11 years of age in the
      same cohort and compared the groups with and without brain sparing.
      DESIGN/METHODS: One hundred sixteen survivors included in a study on the outcome
      of preterm infants born at <33 weeks' gestation with and without fetal brain
      sparing and admitted to the NICU were followed extensively. Ninety-eight infants
      (85%) were again assessed at 11 years of age. Data were available for fetal
      Doppler measurements indicating brain sparing, neonatal cerebral ultrasound
      scanning, and developmental outcome in the first 5 years. Mean birth weight was
      1303 g; mean gestational age was 29.8 weeks. The infants were divided into 2
      groups with and without brain sparing. Visual functioning was estimated by
      measuring visual acuity, visual fields, eye position, and binocular function and
      by visual motor tests. RESULTS: Six percent of the children were found to have a
      visual acuity of <0.8, 12% had strabismus, and 14% to 46% showed abnormal results
      on the visual motor tests. No statistical differences were found between the 2
      groups. However, children with severe cerebral ultrasound diagnoses in the
      neonatal period were found to have significantly more abnormalities on visual
      functioning and lower scores on visual motor tests than children without these
      morbidities. CONCLUSIONS: Children with fetal brain sparing do not demonstrate a
      different development of their visual functioning at late school age. However, an
      abnormal cerebral ultrasound in the neonatal period is associated with impaired
      visual function in later life.

PMID- 17545365
TI  - Between stillness and story: lessons of children's illness narratives.
AB  - In answer to an increasingly impersonal medical environment, educators in the
      medical humanities frequently turn to narrative studies to teach students for an
      emotionally fulfilling and interpersonally related professional practice.
      However, to elicit, to interpret, and to integrate patient stories into their
      work effectively, physicians must be in a state of awareness and attention,
      attuned to their emotional and intellectual reactions. The experiences of
      children and their families, in the form of pediatric illness narratives, hold
      unique insights for physicians in how to engage in an ethical, empathetic, and
      self-reflective practice. In particular, these narratives demonstrate the
      importance not only of story but also of stillness or silence to the practice of
      medicine. The voices of patients and their families hold both literal and
      allegorical lessons for physicians in how to move toward a medical practice
      involving not only diagnosis and treatment but also recognition and healing.

PMID- 17545366
TI  - Go ahead punk, make my day: it's time for pediatricians to take action against
      media violence.

PMID- 17545367
TI  - Incidence of acute otitis media and sinusitis complicating upper respiratory
      tract infection: the effect of age.
AB  - Infants and young children are prone to developing upper respiratory tract
      infections, which often result in bacterial complications such as acute otitis
      media and sinusitis. We evaluated 623 upper respiratory tract infection episodes
      in 112 children (6-35 months of age) to determine the proportion of upper
      respiratory tract infection episodes that result in acute otitis media or
      sinusitis. Of all upper respiratory tract infections, 30% were complicated by
      acute otitis media and 8% were complicated by sinusitis. The rate of acute otitis
      media after upper respiratory tract infection declined with increasing age,
      whereas the rate of sinusitis after upper respiratory tract infection peaked in
      the second year of life. Risk for acute otitis media may be reduced substantially
      by avoiding frequent exposure to respiratory viruses (eg, avoidance of day care
      attendance) in the first year of life.

PMID- 17545368
TI  - Electronic prescribing systems in pediatrics: the rationale and functionality
      requirements.
AB  - This technical report discusses electronic prescribing systems and their
      limitations and potential benefits, particularly to the pediatrician in the
      ambulatory setting. In the report we acknowledge the benefits of integrating
      these systems with electronic health records and practice-management systems and
      recommend that the adoption of electronic prescribing systems be done in the
      context of ultimately moving toward an electronic health record. This technical
      report supports the accompanying American Academy of Pediatrics policy-statement
      recommendations on the adoption of electronic prescribing systems by
      pediatricians.

PMID- 17545369
TI  - Use of sleep medications in hospitalized pediatric patients.
AB  - OBJECTIVE: Little is known about the medications prescribed for sleep in
      hospitalized children. The aims of this study were to (1) determine the
      percentage of hospitalized children who receive medication for sleep
      disturbances, (2) determine what medications are prescribed for sleep
      difficulties, and (3) examine medical and demographic variables related to
      medications prescribed during hospitalization. PATIENTS AND METHODS: A chart
      review was conducted for all inpatients at 3 pediatric hospitals across 26
      randomly selected days in 2004. Demographic, medical, and medication data were
      collected on 9440 patients. The sample was 54.5% male, had a mean age of 7.0
      years, and was 63% white. Almost 19% of the patients had at least 1 psychiatric
      diagnosis. RESULTS: Overall, 6.0% of all hospitalized children (3% of all
      medically hospitalized children, excluding children with a psychiatric diagnosis)
      were prescribed medications for sleep, with antihistamines the most frequently
      prescribed medication (36.6%), followed by benzodiazepines (19.4%); hypnotic
      agents were the least frequently prescribed (2.2%). Significant differences were
      found in both the frequency of sleep-medication prescriptions and the types of
      medications used across hospitals, as well as for age, length of hospitalization,
      and service that the child was discharged from. Children with a psychiatric
      diagnosis were more likely to receive a sleep medication, with 22% of children on
      a psychiatric service receiving a sleep-related medication. CONCLUSIONS:
      Approximately 3% to 6% of children are treated pharmacologically with a broad
      array of sleep medications in hospital settings. Prescription practices vary by
      hospital, medical service, child age, and diagnosis. The results from this study
      indicate that medications are being prescribed for sleep in hospitalized
      children, especially in children with psychiatric diagnoses. However, given that
      there are neither Food and Drug Administration-approved sleep medications for
      children nor clinical consensus guidelines regarding their use, clinical trials,
      practice guidelines, and additional research are clearly needed.

PMID- 17545370
TI  - Compliance with alarm limits for pulse oximetry in very preterm infants.
AB  - OBJECTIVE: The objective of this study was to determine the rate of compliance
      with hospital guidelines for alarm limits for pulse oximetry in preterm infants
      on oxygen therapy. METHODS: All infants admitted to the nurseries at the Royal
      Women's Hospital, Melbourne, Australia, with gestational age <32 weeks or birth
      weight <1500 g between August 2005 and February 2006 were eligible for inclusion.
      Data on the alarm limits set for infants on oxygen therapy were collected
      prospectively. The target saturation range recommended in written hospital
      guidelines was 88% to 92%, with alarm limits set at 85% and 94%. RESULTS: Data
      were prospectively collected for 144 subjects with mean (SD) gestational age 29.3
      (2.4) weeks and birth weight 1226 (354) g; 1073 alarm limits were collected when
      infants were on oxygen. The lower alarm limit was set correctly 91.1% of the
      time. In contrast, the upper alarm limit was set correctly only 23.3% of the
      time: 76.5% of the time it was too high, and 23.8% of the time it was set at
      100%. Infants with an upper alarm limit set correctly on a particular day had a
      significantly lower birth weight, gestational age, postmenstrual age, and
      postnatal age than infants who had the upper alarm limit set too high. Use of
      assisted ventilation, higher inspired oxygen concentrations, and more frequent
      changes in inspired oxygen concentration were all associated with improved odds
      of having an appropriately set upper alarm limit. CONCLUSIONS: This study
      suggests that current guidelines regarding the upper pulse oximeter alarm limit
      for infants receiving oxygen might be commonly exceeded, although compliance
      might be better for infants at higher risk of adverse outcomes. However, there
      might be less variation from guidelines for the lower alarm limit.

PMID- 17545371
TI  - A national outbreak of Ralstonia mannitolilytica associated with use of a
      contaminated oxygen-delivery device among pediatric patients.
AB  - OBJECTIVES: In August 2005, the Centers for Disease Control and Prevention was
      notified of a Ralstonia species outbreak among pediatric patients receiving
      supplemental oxygen therapy with the Vapotherm 2000i (Vapotherm, Inc,
      Stevensville, MD). The Vapotherm 2000i is a reusable medical device that was used
      in >900 hospitals in the United States in 2005. Ralstonia are waterborne bacilli
      that have been implicated in hospital-acquired infections. We initiated an
      investigation to determine the source of the outbreak and implement infection
      control and prevention measures. PATIENTS AND METHODS: We performed a case
      control study at 1 hospital and conducted national case findings to obtain
      clinical and environmental samples for laboratory analysis. Case-patients had
      health care-acquired Ralstonia colonization or infection. Isolates were compared
      by using pulsed-field gel electrophoresis. We tested manufacturer-recommended
      disinfection protocols for the Vapotherm 2000i under simulated-use conditions.
      RESULTS: Case-patients at the hospital (n = 5) were more likely to have received
      Vapotherm therapy than controls. Nationally, Ralstonia mannitolilytica was
      confirmed in 38 patients (aged 5 days to 7 years); 35 (92%) of the patients were
      exposed to the Vapotherm 2000i before recovery of the organism. Pulsed-field gel
      electrophoresis showed related R. mannitolilytica strains from isolates sent from
      18 hospitals in 12 states. A Vapotherm machine reprocessed with a protocol
      proposed by the manufacturer grew Ralstonia spp after 7 days of simulated use. In
      December 2005, Vapotherm recalled the 2000i. CONCLUSIONS: Our findings suggest
      intrinsic contamination of Vapotherm devices with Ralstonia spp. New medical
      devices may provide therapy equivalent to current devices yet pose novel
      reprocessing challenges.

PMID- 17545372
TI  - Temporal relationships between colds, upper respiratory viruses detected by
      polymerase chain reaction, and otitis media in young children followed through a
      typical cold season.
AB  - INTRODUCTION: Otitis media is a frequent complication of a viral upper
      respiratory tract infection, and the reported co-incidence of those diseases
      increases with assay sensitivity and sampling density. We determined the
      incidence of otitis-media complications in young children when referenced to cold
      like illnesses and to concurrent virus recovery from the nasopharynx. METHODS: A
      total of 60 children from 24 families were followed from October 2003 through
      April 30, 2004, by daily parental recording of illness signs, weekly pneumatic
      otoscopic examinations, and periodic polymerase chain reaction assay of collected
      nasal fluids for common viruses. RESULTS: One hundred ninety-nine cold-like
      illnesses were observed, but a sample for virus assay was not collected
      concurrent with 71 episodes. Of the remainder, 73% of cold-like illnesses were
      temporally related to recovery of 1 or a combination of the assayed viruses, with
      rhinovirus predominating. For non-cold-like illness periods, 54 (18%) of 297
      assays were positive for virus, and the virus frequency distribution was similar
      to that for cold-like illnesses. There were 93 diagnosed otitis-media episodes;
      65 (70%) of these occurred during a cold-like illness. For the 79 otitis-media
      episodes with available nasal samples, 61 (77%) were associated with a positive
      virus result. In this population, the otitis-media complication rate for a cold
      like illness was 33%. CONCLUSIONS: A cold-like illness was not a prerequisite for
      polymerase chain reaction detection of viruses in the nose and nasopharynx of
      young children. Viral detection by polymerase chain reaction in the absence of a
      cold-like illness is associated with complications in some subjects. Otitis media
      is a complication of viral infection both with and without concurrent cold-like
      illnesses, thus downwardly biasing coincidence estimates that use cold-based
      illnesses as the denominator.

PMID- 17545373
TI  - Immunogenicity and safety of intradermal influenza immunization at a reduced dose
      in healthy children.
AB  - OBJECTIVES: We conducted this study to test the hypothesis that intradermal
      influenza vaccination at one fifth of a standard dose elicits comparable
      immunogenicity to full-dose intramuscular vaccination in children. PATIENTS AND
      METHODS: We conducted a randomized, open-label study in 112 healthy children aged
      3 to <18 years to compare the immunogenicity and safety of intradermal
      vaccination at one fifth of a dose with standard intramuscular vaccination.
      Analyses of hemagglutination inhibition antibody titers to each antigen in each
      group included geometric mean titers before and 21 days after vaccination, fold
      increase in geometric mean titers after vaccination, seroprotection rate, and
      seroconversion rate. RESULTS: The mean age of the subjects was 10.11 +/- 4.04
      years in the intradermal vaccination group and 10.57 +/- 3.91 years in the
      intramuscular group. Intradermal vaccination was safe. Induration and mild
      erythema at the injection site were reported at 25% and 57%, respectively, in the
      intradermal group. Fold increase of geometric mean titers against influenza
      A/Caledonia was robust in both groups (11.1-fold and 12.9-fold increase in the
      intramuscular and intradermal groups, respectively), whereas that for B/Shandong
      was more modest (4.3-4.4). Both approaches elicited very high geometric mean
      titers against influenza A/Panama: 1360.5 and 893.9 for the intramuscular and
      intradermal groups, respectively, but because the prevaccination antibody titers
      were high, the fold increase of geometric mean titers was only 4.5 and 2.6,
      respectively. CONCLUSION: The immunogenicity of one fifth of a dose of influenza
      vaccine delivered by the intradermal route is comparable to the standard-dose
      intramuscular vaccination in children as young as 3 years of age.

PMID- 17545374
TI  - Statistical literacy for readers of Pediatrics: a moving target.
AB  - OBJECTIVE: Pediatric residents are expected to study research design and
      statistical methods to enable them to critically appraise the pediatric
      literature and apply the findings to patient care. However, it is not clear how
      best to teach these skills or even which statistical concepts are most important.
      An earlier study demonstrated that the statistical complexity of articles
      published in Pediatrics increased from 1952 to 1982. The goals of our study were
      to assess whether this trend has continued and to determine the statistical
      measures and procedures most commonly encountered in Pediatrics. METHODS: We
      reviewed the print research articles published in Pediatrics, volume 115, 2005,
      and recorded the statistical measures and procedures reported in each article to
      determine how many articles used statistics or statistical procedures and what
      statistical procedures were encountered most commonly. RESULTS: The proportion of
      articles that used any inferential statistics increased from 48% in 1982 to 89%
      in 2005. The mean number of inferential procedures per article increased from 2.5
      in 1982 to 3.9 in 2005. The most commonly encountered statistical procedures or
      measures were descriptive statistics, tests of proportions, measures of risk,
      logistic regression, t tests, nonparametric tests, analysis of variance, multiple
      linear regression, sample size and power calculation, and tests of correlation.
      However, a reader who is familiar with only these concepts can understand the
      analyses used in only 47% of articles. CONCLUSIONS: Our results confirm a trend
      toward the use of new and increasingly complex statistical techniques in
      Pediatrics. Educational efforts might most profitably focus on the principles
      underlying statistical analysis rather than on specific statistical tests.
      Authors, reviewers, and journal editors have a greater responsibility for
      ensuring that statistical procedures are used appropriately, as it may be
      increasingly unrealistic to expect readers to fully understand the statistical
      analyses used in journal articles.

PMID- 17545375
TI  - Relationship between angiotensin-converting enzyme gene insertion or deletion
      polymorphism and insulin sensitivity in healthy newborns.
AB  - CONTEXT: It was proposed that the association between low birth weight and adult
      insulin resistance is principally genetically mediated. The insertion/deletion
      polymorphism of the angiotensin-converting enzyme gene was associated with
      insulin sensitivity in adults. OBJECTIVE: Our goal was to investigate the
      relationship between angiotensin-converting enzyme gene insertion/deletion
      polymorphism and the insulin sensitivity in healthy newborns. PATIENTS AND
      METHODS: One hundred eighty healthy newborns, all of whom had a 1-minute Apgar
      score of > 7 and gestational age > 33 weeks, were enrolled in the study. Fasting
      glucose and insulin levels were measured on day 2 or 3 after birth, and
      angiotensin-converting enzyme genotype was determined. RESULTS: The observed
      frequency distribution of angiotensin-converting enzyme genotypes did not deviate
      from that predicted by Hardy-Weinberg equilibrium in this group. There were no
      statistically significant differences in birth size and shape in different
      angiotensin-converting enzyme genotypes. Those carriers of the genotype
      homozygous for the deletion allele had the highest logarithmically transformed
      homeostasis model assessment compared with those who were heterozygous or
      homozygous for the insertion polymorphism. When compared with those with > or = 1
      insertion allele, those of the genotype homozygous for the deletion allele had
      significantly higher logarithmically transformed fasting insulin and
      logarithmically transformed homeostasis model assessment results. Regarding birth
      weight, birth length, ponderal index, and fasting glucose concentration, there
      were no significant differences between the genotype homozygous for the deletion
      allele and the genotypes heterozygous or homozygous for the insertion allele.
      CONCLUSIONS: In this study, the deletion allele was associated with relatively
      impaired insulin sensitivity in healthy neonates. It may be a clue to explain the
      association between the deletion allele and insulin resistance in the long-term.

PMID- 17545376
TI  - Infant swimming practice, pulmonary epithelium integrity, and the risk of
      allergic and respiratory diseases later in childhood.
AB  - OBJECTIVE: Irritant gases and aerosols contaminating the air of indoor swimming
      pools can affect the lung epithelium and increase asthma risk in children. We
      evaluated the impact of infant swimming practice on allergic status and
      respiratory health later in childhood. METHODS: Clara cell protein, surfactant
      associated protein D, and total and aeroallergen-specific immunoglobulin E were
      measured in the serum of 341 schoolchildren aged 10 to 13 years, among whom 43
      had followed an infant swimming program. Asthma was defined as doctor-diagnosed
      asthma and/or positive exercise-induced bronchoconstriction (15% decrease in
      postexercise forced expiratory volume). RESULTS: There were no significant
      differences between the infant swimming group and the other children regarding
      the levels of exhaled nitric oxide and total or aeroallergen-specific serum
      immunoglobulin E. Children who swam as infants showed, by contrast, a significant
      decrease of serum Clara cell protein and of the serum Clara cell
      protein/surfactant-associated protein D ratio integrating Clara cell damage and
      permeability changes of the lung epithelial barrier. These effects were
      associated with higher risks of asthma and of recurrent bronchitis. Passive
      exposure to tobacco alone had no effect on these outcomes but seemed to interact
      with infant swimming practice to increase the risk of asthma or of recurrent
      bronchitis. CONCLUSIONS: Our data suggest that infant swimming practice in
      chlorinated indoor swimming pools is associated with airways changes that, along
      with other factors, seem to predispose children to the development of asthma and
      recurrent bronchitis.

PMID- 17545377
TI  - Maternal asthma and maternal smoking are associated with increased risk of
      bronchiolitis during infancy.
AB  - OBJECTIVE: Our goal was to determine whether maternal asthma and maternal smoking
      during pregnancy are associated with the incidence and severity of clinically
      significant bronchiolitis in term, otherwise healthy infants without the
      confounding factors of small lung size or underlying cardiac or pulmonary
      disease. PATIENTS AND METHODS: We conducted a population-based retrospective
      cohort study of term, non-low birth weight infants enrolled in the Tennessee
      Medicaid Program from 1995 to 2003. The cohort of infants was followed through
      the first year of life to determine the incidence and severity of bronchiolitis
      as determined by health care visits and prolonged hospitalization. RESULTS: A
      total of 101,245 infants were included. Overall, 20% of infants had > or = 1
      health care visit for bronchiolitis. Compared with infants with neither factor,
      the risk of bronchiolitis was increased in infants with maternal smoking only,
      maternal asthma only, or both. Infants with maternal asthma only or with both
      maternal smoking and asthma had the highest risks for emergency department visits
      and hospitalizations. Infants with a mother with asthma had the highest risk of a
      hospitalization > 3 days, followed by infants with both maternal asthma and
      smoking, and maternal smoking only. CONCLUSIONS: Maternal asthma and maternal
      smoking during pregnancy are independently associated with the development of
      bronchiolitis in term, non-low birth weight infants without preexisting cardiac
      or pulmonary disease. The risk of bronchiolitis among infants with mothers who
      both have asthma and smoke during pregnancy is approximately 50% greater than
      that of infants with neither risk factor. Efforts to decrease the illness
      associated with these 2 risk factors will lead to decreased morbidity from
      bronchiolitis, the leading cause of hospitalization for severe lower respiratory
      tract infections during infancy.

PMID- 17545378
TI  - Laboratory values for children with newly diagnosed inflammatory bowel disease.
AB  - OBJECTIVE: The goal was to determine how often common laboratory tests yield
      normal results at the time of diagnosis for children with inflammatory bowel
      disease. METHODS: Data were obtained from a registry of children with newly
      diagnosed inflammatory bowel disease who were enrolled prospectively in 18
      US/Canadian centers. Laboratory values investigated included hemoglobin level,
      platelet count, albumin level, and erythrocyte sedimentation rate. Disease
      severity was categorized by physician global assessment. RESULTS: A total of 526
      children (mean age: 11.6 years; 58% male; 392 with Crohn disease and 134 with
      ulcerative colitis) were studied. All 4 values were normal for 21% of patients
      with mild Crohn disease and 54% with mild ulcerative colitis. In contrast, only
      3.8% of children with moderate/severe Crohn disease and 4.3% with moderate/severe
      ulcerative colitis had normal results for all 4 tests. The erythrocyte
      sedimentation rate was least likely to be normal; overall, 26% of patients with
      inflammatory bowel disease had a normal erythrocyte sedimentation rate, including
      18% with moderate/severe disease. Hemoglobin levels were normal for 32%, platelet
      counts for 50%, and albumin levels for 60%. There was no clear association
      between Crohn disease location and either severity or number of normal laboratory
      values. In contrast, there were direct correlations between ulcerative colitis
      disease severity and both the extent of bowel inflammation and the number of
      abnormal laboratory tests. CONCLUSION: The presence of normal screening
      laboratory studies should not dissuade clinicians from considering a diagnosis of
      inflammatory bowel disease.

PMID- 17545379
TI  - Role of zinc administration in prevention of childhood diarrhea and respiratory
      illnesses: a meta-analysis.
AB  - BACKGROUND: The quantified effect of zinc supplementation to prevent childhood
      diarrhea and respiratory illnesses is unclear. We conducted a meta-analysis of
      randomized, controlled trials on the subject. METHODS: We searched PubMed,
      Science Citation Index, and the Cochrane Database of Controlled Trials and hand
      searched the reference lists of identified articles. All randomized, controlled
      trials of zinc supplementation for > or = 3 months for children < 5 years of age,
      using blinded assessment, were eligible. The outcome measures studied were number
      of episodes of illness, number of days with illness, and number of episodes of
      severe illness. Data from 17 studies were pooled by using random-effects and
      fixed-effects models for data with and without significant heterogeneity,
      respectively. RESULTS: Children who received a zinc supplement had fewer episodes
      of diarrhea (rate ratio: 0.86) and respiratory tract infections (rate ratio:
      0.92) and significantly fewer attacks of severe diarrhea or dysentery (rate
      ratio: 0.85), persistent diarrhea (rate ratio: 0.75), and lower respiratory tract
      infection or pneumonia (rate ratio: 0.80) than did those who received placebo.
      They also had significantly fewer total days with diarrhea (rate ratio: 0.86) but
      not days with respiratory illness (rate ratio: 0.95). Published studies showed a
      publication bias and significant heterogeneity; however, no cause for the latter
      could be identified. CONCLUSIONS: Zinc supplementation reduced significantly the
      frequency and severity of diarrhea and respiratory illnesses and the duration of
      diarrheal morbidity. The relatively limited reduction in morbidity and the
      presence of significant heterogeneity and of publication bias indicate the need
      for larger, high-quality studies to identify subpopulations most likely to
      benefit.

PMID- 17545380
TI  - Quality of primary care and subsequent pediatric emergency department
      utilization.
AB  - OBJECTIVE: Our objective was to determine whether parent-reported, high-quality
      primary care was associated with decreased nonurgent pediatric emergency
      department utilization. METHODS: A retrospective analysis of prospectively
      collected data for a cohort of children from the 2000-2001 and 2001-2002 Medical
      Expenditure Panel Survey panels was performed. Baseline parent-reported quality
      of primary care with respect to family-centeredness, timeliness, and realized
      access (a measure of the child's ability to receive necessary care and referrals)
      was assessed by using composite scores from the Consumer Assessment of Healthcare
      Providers and Systems survey. The primary outcomes were the numbers of subsequent
      nonurgent and urgent emergency department visits per child. RESULTS: Of 8823
      children included, 70.0% rated family-centeredness, 88.2% rated realized access,
      and 55.6% rated timeliness as high quality. After adjustment for demographic
      factors and health status, high-quality family-centeredness was associated with a
      42% reduction in nonurgent emergency department visits for publicly insured
      children and a 49% reduction for children < or = 2 years of age. Greater realized
      access was associated with a 44% reduction in nonurgent emergency department
      visits for children 3 to 11 years of age and a 56% reduction for children > or =
      12 years of age. Greater realized access was also associated with decreased
      nonurgent emergency department visits for publicly and privately insured children
      (37% and 35%, respectively). There was no significant association between
      timeliness and nonurgent emergency department utilization, nor was any quality-of
      care domain associated with urgent emergency department utilization. CONCLUSIONS:
      Parent-reported, high-quality family-centeredness and a high level of realized
      access to primary care were associated with decreased subsequent nonurgent
      emergency department visits for children. Parent reports of health care quality
      in these domains provide important complementary information on health care
      quality.

PMID- 17545381
TI  - The host hospital 24-hour underreferral rate: an automated measure of call-center
      safety.
AB  - OBJECTIVES: The goals were to (1) define and illustrate an automated method of
      monitoring the safety of telephone triage, (2) demonstrate that this method
      approximates reasonably a more-global safety measure, and (3) describe the month
      to-month variability of this automated measure for the call center studied.
      METHODS: From October 2005 through March 2006, hospitalizations at a tertiary
      care pediatric hospital after calls to its call center were matched with their
      respective call-center dispositions. The host hospital 24-hour underreferral rate
      was defined as the percentage of total admissions to the study institution within
      24 hours after a call to the call center for treatment of the same illness or
      injury that had been assigned a nonurgent disposition by the call center. A
      convenience sample of call-center calls was surveyed for admissions to other
      facilities. This sample was then combined with admissions to the pediatric
      hospital to estimate a true 24-hour underreferral rate. Underreferrals were
      subjected to clinical and statistical analyses. RESULTS: The host hospital 24
      hour underreferral rate was 5.2%. The estimated true 24-hour underreferral rate
      was 5.95% +/- 2.75%. Diagnoses frequently associated with underreferral were
      gastroenteritis, croup, asthma, and bronchiolitis. Underreferred patients
      admitted to the study institution were hospitalized for an average of 1.6 +/- 1.1
      days, compared with 2.8 +/- 3.1 days for patients referred by the call center to
      a higher level of care. The monthly SD of the host hospital 24-hour underreferral
      rate was 1.56%. CONCLUSIONS: For the call center studied, the host hospital 24
      hour underreferral rate could be determined easily and objectively and
      approximated reasonably the true 24-hour underreferral rate. The month-to-month
      variability of the host hospital 24-hour underreferral rate was sufficiently
      small to allow for meaningful internal trending analyses.

PMID- 17545382
TI  - Intensive home visiting is associated with decreased risk of infant death.
AB  - OBJECTIVE: The goal was to test the hypothesis that participation in a community
      based home-visiting program is associated with a decreased risk of infant death.
      METHODS: A retrospective, case-control design was used to compare the risk of
      infant death among participants in Cincinnati's Every Child Succeeds program and
      control subjects matched for gestational age at birth, previous pregnancy loss,
      marital status, and maternal age. The likelihood of infant death, adjusted for
      level of prenatal care, maternal smoking, maternal education, race, and age, was
      determined with multivariate logistic regression. The interaction between race
      and program participation and the effect of home visiting on the risk of preterm
      birth were explored. RESULTS: Infants whose families did not receive home
      visiting (n = 4995) were 2.5 times more likely to die in infancy compared with
      infants whose families received home visiting (n = 1665). Black infants were at
      least as likely to benefit from home visiting as were nonblack infants. No effect
      of program participation on the risk of preterm birth was observed. CONCLUSION:
      The current study is consistent with the hypothesis that intensive home visiting
      reduces the risk of infant death.

PMID- 17545383
TI  - Endothelial function in newborn infants is related to folate levels and birth
      weight.
AB  - OBJECTIVE: Low maternal folate levels during pregnancy correlate with low birth
      weight, a perinatal risk factor for later cardiovascular disease. We studied
      relationships between red blood cell folate levels, birth weight, and vascular
      endothelial function (a key factor in the early pathophysiologic processes of
      heart disease) in newborn infants. METHODS: We included 82 infants (30 low birth
      weight) and their mothers. A laser Doppler technique was used to measure skin
      perfusion during transdermal iontophoresis of acetylcholine (an endothelium
      dependent vasodilator). Red blood cell folate, vitamin B12, and homocysteine
      levels were determined. RESULTS: The perfusion response to acetylcholine was
      lower in low birth weight infants than in normal birth weight control subjects
      (mean: 35 vs 76 perfusion units). The neonatal acetylcholine response correlated
      with red blood cell folate levels in both infants and their mothers. The folate
      levels of low birth weight and control infants did not differ significantly
      (mean: 1603 vs 1795 nmol/L), but mothers of low birth weight infants had lower
      folate levels than did mothers of control infants (mean: 805 vs 1109 nmol/L). In
      multivariate analysis, low birth weight and red blood cell folate levels
      contributed independently to endothelial function in newborn infants. The levels
      of vitamin B12 and homocysteine were similar in the 2 groups and did not
      correlate with endothelial function. CONCLUSION: The data presented here provide
      the first evidence for a relationship between folate levels and vascular
      endothelial function in newborn infants.

PMID- 17545384
TI  - Inhaled nitric oxide therapy decreases the risk of cerebral palsy in preterm
      infants with persistent pulmonary hypertension of the newborn.
AB  - OBJECTIVE: The aim was to determine whether inhaled nitric oxide therapy improves
      neurodevelopmental outcomes for infants with preterm persistent pulmonary
      hypertension of the newborn. METHODS: We conducted a historical cohort study to
      compare the 3-year incidence of cerebral palsy in preterm singleton infants (< 34
      gestational weeks) with hypoxemic respiratory failure caused by persistent
      pulmonary hypertension of the newborn who received inhaled nitric oxide (16
      patients) or 100% oxygen (15 patients) therapy. All neonates had clinical and
      echocardiographic evidence of pulmonary hypertension without structural heart
      disease. RESULTS: The incidence of cerebral palsy among patients treated with
      inhaled nitric oxide was 12.5%, whereas that among patients treated with 100%
      oxygen was 46.7%. After adjustment for maternal fever (> or = 38 degrees C)
      during delivery, birth weight, Apgar score at 5 minutes, high-frequency
      oscillatory ventilation, and surfactant therapy, inhaled nitric oxide therapy,
      compared with 100% oxygen therapy, was associated with a decreased risk of
      cerebral palsy in preterm infants with persistent pulmonary hypertension of the
      newborn. CONCLUSION: Inhaled nitric oxide therapy decreases the risk of cerebral
      palsy in preterm infants with persistent pulmonary hypertension of the newborn.

PMID- 17545385
TI  - Patent ductus arteriosus and its treatment as risk factors for neonatal and
      neurodevelopmental morbidity.
AB  - OBJECTIVES: The purpose of this work was to determine whether the reported
      association between neonatal morbidities and a patent ductus arteriosus is
      because of the left-to-right patent ductus arteriosus shunt itself, the therapies
      used to treat it, or the immaturity of the infants who are likely to develop a
      patent ductus arteriosus. METHODS: A total of 446 infants (<28 weeks' gestation)
      were treated with the same patent ductus arteriosus care-oriented protocol, and
      logistic regression analysis was used to examine the effects of several patent
      ductus arteriosus-related variables (presence of a symptomatic patent ductus
      arteriosus, the number of indomethacin doses used, the ductus response to
      indomethacin, and the use of surgical ligation) on the incidence of retinopathy
      of prematurity, necrotizing enterocolitis, chronic lung disease, death, and
      neurodevelopmental impairment. RESULTS: Most of the predictive effects that the
      presence of a patent ductus arteriosus and its treatment had on neonatal
      morbidity could be accounted for by the infants' immature gestation. Use of
      surgical ligation, however, was significantly associated with the development of
      chronic lung disease and was independent of immature gestation, other patent
      ductus arteriosus-related variables, or other perinatal and neonatal risk factors
      known to be associated with chronic lung disease. CONCLUSIONS: These findings add
      to the growing uncertainty about the benefits and risks of surgical ligation
      during the neonatal period.

PMID- 17545386
TI  - Continuity of health insurance coverage among young adults with disabilities.
AB  - OBJECTIVES: Although considered critical to facilitate the successful transition
      from pediatric to adult health care, the continuity of insurance coverage for
      young adults with disabilities as they make the transition to adulthood has not
      been well characterized. The purpose of this work was to compare the continuity
      of insurance coverage reported by a nationally representative sample of young
      adults 16 to 25 years old with and without disabilities during a consecutive 36
      month period. METHODS: We performed secondary analysis of data from the 2001
      Survey of Income Program and Participation. Data for the survey were collected at
      4-month intervals from February 2001 through January 2004 for 5170 young adults.
      Subjects with disabilities were those who reported limitations in activities of
      daily living or work, used assistive devices, and/or had learning disabilities,
      mental retardation, or other mental disorders. The primary outcome was
      uninsurance defined for each study month in which there was no coverage by
      private, public, or military programs. We present bivariate analyses of the
      months of uninsurance according to disability status using longitudinal weights
      and design-effect adjustments to account for the complex sample design. RESULTS:
      The sample consisted of 599 subjects with and 4571 without reported disabilities,
      representing 3,970,000 and 30,800,000 young adults in the United States,
      respectively. At study entry, 22% of the young adults with disabilities were
      uninsured. During the 36-month follow-up period, 56% of the young adults with
      disability reported gaps in insurance coverage with a mean of 15 months of
      uninsurance. The proportion of uninsured subjects did not significantly differ by
      disability status. CONCLUSIONS: The majority of young adults with disabilities
      reported gaps in insurance coverage, and many were uninsured for a substantial
      portion of the study period. As an increasing number of children with special
      health care needs make the transition to adulthood, improving the continuity of
      health insurance coverage for this population warrants specific attention.

PMID- 17545387
TI  - Neonatal intensive care unit oxygen management: a team effort.

PMID- 17545388
TI  - Drug pricing in pediatrics: the egregious example of indomethacin.

PMID- 17545389
TI  - Counseling youth about military service options and Selective Service
      registration: an integral part of anticipatory guidance of adolescents.

PMID- 17545390
TI  - Pediatric prevention of atherosclerosis: targeting early variation in vascular
      biology.

PMID- 17545391
TI  - Providing a safety net for children: investigating a multistate outbreak of
      Ralstonia mannitolilytica related to a contaminated reusable device.

PMID- 17545392
TI  - Maternal smoking, asthma, and bronchiolitis: clear-cut association or equivocal
      evidence?

PMID- 17545393
TI  - The success of an immunization information system in the wake of Hurricane
      Katrina.
AB  - Within days after Hurricane Katrina in September 2005, the Houston-Harris County
      Immunization Registry was connected to the Louisiana Immunization Network for
      Kids Statewide. This linkage provided immediate access to the immunization
      records of children who were forced to evacuate the New Orleans, Louisiana, area.
      One year later, >18,900 immunization records have been found, representing an
      estimated cost savings of more than $1.6 million for vaccine alone and $3.04
      million for vaccine plus administration fees. This experience demonstrated the
      vital and previously unrecognized functionality of immunization information
      systems in a public health emergency. Here we describe the Houston-Harris County
      Immunization Registry's experience after Hurricane Katrina in terms of maximizing
      the use of immunization information systems and the implications of this
      experience for patients, providers, and public health for future disaster
      preparedness planning.

PMID- 17545394
TI  - Provision of educationally related services for children and adolescents with
      chronic diseases and disabling conditions.
AB  - Children and adolescents with chronic diseases and disabling conditions often
      need educationally related services. As medical home providers, physicians and
      other health care professionals can assist children, adolescents, and their
      families with the complex federal, state, and local laws, regulations, and
      systems associated with these services. Expanded roles for physicians and other
      health care professionals in individualized family service plan, individualized
      education plan, and Section 504 plan development and implementation are
      recommended. Recent updates to the Individuals With Disabilities Education Act
      will also affect these services. Funding for these services by private and
      nonprivate sources also continue to affect the availability of these
      educationally related services. The complex range of federal, state, and local
      laws, regulations, and systems for special education and related services for
      children and adolescents in public schools is beyond the scope of this statement.
      Readers are referred to the American Academy of Pediatrics policy statement "The
      Pediatrician's Role in Development and Implementation of an Individual Education
      Plan (IEP) and/or an Individual Family Service Plan (IFSP)" for additional
      background materials. The focus of this statement is the role that health care
      professionals have in determining and managing educationally related services in
      the school setting. This policy statement is a revision of a previous statement,
      "Provision of Educationally Related Services for Children and Adolescents With
      Chronic Diseases and Disabling Conditions," published in February 2000 by the
      Committee on Children With Disabilities
      (http://aappolicy.aappublications.org/cgi/content/full/pediatrics;105/2/448).

PMID- 17545395
TI  - State Children's Health Insurance Program achievements, challenges, and policy
      recommendations.
AB  - This policy statement reviews the impressive progress of the State Children's
      Health Insurance Program since its enactment in 1997 and identifies outstanding
      challenges and state and federal policy recommendations. The American Academy of
      Pediatrics urges Congress to reauthorize SCHIP to strengthen its historic gains.
      The following set of recommended strategies for reauthorization pertain to
      funding, eligibility and enrollment, coverage, cost sharing, payment and provider
      network capacity, and quality performance.

PMID- 17545396
TI  - Electronic prescribing systems in pediatrics: the rationale and functionality
      requirements.
AB  - The use of electronic prescribing applications in pediatric practice, as
      recommended by the federal government and other national health care improvement
      organizations, should be encouraged. Legislation and policies that foster
      adoption of electronic prescribing systems by pediatricians should recognize both
      specific pediatric requirements and general economic incentives required to speed
      the adoption of these systems. Continued research into improving the
      effectiveness of these systems, recognizing the unique challenges of providing
      care to the pediatric population, should be promoted.

PMID- 17545397
TI  - Evaluation of suspected child physical abuse.
AB  - This report provides guidance in the clinical approach to the evaluation of
      suspected physical abuse in children. The medical assessment is outlined with
      respect to obtaining a history, physical examination, and appropriate ancillary
      testing. The role of the physician may encompass reporting suspected abuse;
      assessing the consistency of the explanation, the child's developmental
      capabilities, and the characteristics of the injury or injuries; and coordination
      with other professionals to provide immediate and long-term treatment and follow
      up for victims. Accurate and timely diagnosis of children who are suspected
      victims of abuse can ensure appropriate evaluation, investigation, and outcomes
      for these children and their families.

PMID- 17545398
TI  - Overuse injuries, overtraining, and burnout in child and adolescent athletes.
AB  - Overuse is one of the most common etiologic factors that lead to injuries in the
      pediatric and adolescent athlete. As more children are becoming involved in
      organized and recreational athletics, the incidence of overuse injuries is
      increasing. Many children are participating in sports year-round and sometimes on
      multiple teams simultaneously. This overtraining can lead to burnout, which may
      have a detrimental effect on the child participating in sports as a lifelong
      healthy activity. One contributing factor to overtraining may be parental
      pressure to compete and succeed. The purpose of this clinical report is to assist
      pediatricians in identifying and counseling at-risk children and their families.
      This report supports the American Academy of Pediatrics policy statement on
      intensive training and sport specialization.

PMID- 17545399
TI  - Score for Neonatal Acute Physiology (SNAP) or Vermont Oxford risk-adjustment
      model for very low birth weight infants?

PMID- 17545400
TI  - Asthma as a barrier to children's physical activity.

PMID- 17545401
TI  - Subarachnoid hemorrhage in a young child with sickle cell disease: is
      transcranial Doppler helpful?

PMID- 17545402
TI  - Neonatal brain volumetric studies: regression analysis and interpretation.

PMID- 17545403
TI  - Early autism identification.

PMID- 17545404
TI  - Marketing foods and beverages: why licensed commercial characters should not be
      used to sell healthy products to children.

PMID- 17545405
TI  - Mycoplasma pneumoniae encephalitis and reactivation of herpes simplex virus.

PMID- 17545406
TI  - Give Synagis via home care: a reply.

PMID- 17545407
TI  - Pulling the plug on entertainment industry ratings.

PMID- 17545408
TI  - Adverse events in the manipulation of pediatric patients: flaws in a systematic
      review.

PMID- 17545409
TI  - Adverse events in the manipulation of pediatric patients: flaws in a systematic
      review.

PMID- 17545410
TI  - Adverse events in the manipulation of pediatric patients: flaws in a systematic
      review.

PMID- 17545411
TI  - Noninitiation or withdrawal of intensive care for high-risk newborns.

PMID- 17545412
TI  - Neonatal blue-light phototherapy could increase the risk of dysplastic nevus
      development.

PMID- 17545413
TI  - Beyond pleasure: emotion activity affects the relationship between attitudes and
      behavior.
AB  - The research examined an additional proposed moderator of the attitude-behavior
      relationship: the activity level of emotions associated with an attitude object.
      In Experiment 1, participants who self-generated active rather than passive
      emotions as being associated with gay men displayed greater attitude-behavior
      consistency in hiring recommendations for a gay job applicant, as did
      participants who rated active rather than passive experimenter-provided emotions
      as being associated with gay men. In Experiment 2, participants who were
      instructed to associate active rather than passive emotions with gay men
      subsequently displayed greater attitude-behavior consistency in similar hiring
      recommendations. It is suggested that future research on the affective component
      of attitudes might benefit from going beyond consideration of whether the
      associated emotions entail displeasure or pleasure.

PMID- 17545414
TI  - Discordant evaluations of Blacks affect nonverbal behavior.
AB  - Previous research suggests that automatic prejudice directly manifests in
      nonverbal behavior. The authors offer a more complex picture of the relation
      between automatic processes and nonverbal behavior by suggesting that any
      discomfort that appears in nonverbal behavior stems not from negative attitudes
      per se but from discordance between automatically activated attitudes toward
      Blacks and the specific evaluations being expressed. White participants for whom
      estimates of automatic prejudice were available provided videotaped evaluations
      of several individuals, including two matched Black and White males. Discordance
      between general racial attitudes and evaluations of specific targets manifested
      in discomfort-related nonverbal behavior. Moreover, naive Black judges, but not
      White judges, doubted the sincerity of individuals characterized by discordance.
      The nature of the nonverbal "leakage" that automatic prejudice produces is
      discussed.

PMID- 17545415
TI  - Terror mismanagement: evidence that mortality salience exacerbates phobic and
      compulsive behaviors.
AB  - Terror management theory (TMT) posits that cultural worldviews and self-esteem
      function to buffer humans from mortality-related anxiety. TMT research has shown
      that important behaviors are influenced by mortality salience (MS) even when they
      have no obvious connection to death. However, there has been no attempt to
      investigate TMT processes in anxious responding. The present research examines
      that question. In Study 1, compared to a control condition, MS increased anxious
      responding to spider-related stimuli, but only for participants who met criteria
      for specific phobia. In Study 2, compared to an aversive control condition, MS
      increased time spent washing hands, but only for those scoring high on a measure
      of compulsive hand washing (CHW). In Study 3, compared to a different aversive
      control condition, MS increased avoidance of a social interaction, but only for
      those scoring high on a measure of social interaction anxiety. The relevance of
      TMT in anxious responding is discussed.

PMID- 17545416
TI  - Early pain relief and function after posterior minimally invasive and
      conventional total hip arthroplasty. A prospective, randomized, blinded study.
AB  - BACKGROUND: Few prospective randomized studies have demonstrated benefits of
      minimally invasive total hip arthroplasty when compared with conventional total
      hip arthroplasty. We hypothesized that patients treated with a posterior mini
      incision would have better results than those treated with a posterior long
      incision with regard to the achievement of established goals for pain relief and
      functional recovery permitting hospital discharge by the second postoperative
      day. METHODS: Sixty of 231 eligible patients were randomized (with thirty in each
      group) to have a total hip arthroplasty performed through either a posterior mini
      incision (10 +/- 2 cm) or a traditional long incision (20 +/- 2 cm). After
      completion of the total hip arthroplasty, the mini-incision group underwent
      extension of the skin incision to 20 cm. Patients were evaluated on the basis of
      self-determined pain scores, requirements for pain medicine, need for assistive
      gait devices, and time until discharge. Gait analysis provided objective
      functional assessment. RESULTS: The average hospital stay was 63.2 +/- 13.3 hours
      in the mini-incision group and 73.6 +/- 23.5 hours in the long-incision group (p
      = 0.04). More patients with a mini-incision were discharged by the second
      postoperative day (p = 0.003) and more were using just a single assistive device
      at the time of discharge (p = 0.005). As scored on a verbal analog scale of 0 to
      10 points, patients with a mini-incision had less pain on each postoperative day
      and the pain score remained significantly lower at the time of discharge (mean,
      2.2 +/- 1.0 points compared with 3.1 +/- 0.9 points in the long-incision group; p
      = 0.002). After hospital discharge, there were no clinical differences in pain or
      function between the two groups of patients. CONCLUSIONS: Compared with
      conventional total hip arthroplasty performed through a posterior incision,
      posterior minimally invasive total hip arthroplasty resulted in better early pain
      control, earlier discharge to home, and less use of assistive devices. Subsequent
      evaluations at six weeks and three months showed equivalency between the clinical
      results in the two groups. LEVEL OF EVIDENCE: Therapeutic Level I.

PMID- 17545417
TI  - Impact of psychological distress on pain and function following knee
      arthroplasty.
AB  - BACKGROUND: Preoperative psychological distress has been reported to be an
      important risk factor for poor outcome following lower-extremity arthroplasty. We
      determined the independent impact of preoperative psychological distress on
      three, twelve, and twenty-four-month WOMAC (Western Ontario and McMaster
      Universities Osteoarthritis Index) pain and function scores and on change scores
      over those time periods. METHODS: Data were obtained from an international group
      of 952 patients in thirteen centers participating in the Kinemax Outcomes Study.
      Patients completed the WOMAC and Short Form-36 (SF-36) questionnaires. The mental
      health (MH) scale of the SF-36 was used to quantify the impact of psychological
      distress on WOMAC pain and function scores. We also dichotomized patients into
      groups with and without psychological distress on the basis of evidence-based cut
      points. Repeated-measures models were used to derive mean preoperative and three,
      twelve, and twenty-four-month WOMAC pain and function scores and general linear
      models were used to derive change scores for patients with and without
      psychological distress after adjustment for covariates. RESULTS: Psychological
      distress, when examined on a continuous scale, was found to predict pain and
      function at all time-points. WOMAC pain scores for psychologically distressed
      patients were 3 to 5 points lower, depending on the time-frame, than the scores
      for the non-distressed patients, after adjustment for covariates. WOMAC function
      scores did not differ significantly between the two groups following surgery. The
      changes in the WOMAC pain and function scores for the psychologically distressed
      patients were not significantly different from those for the non-distressed
      patients. CONCLUSIONS: Many patients with psychological distress demonstrate a
      substantial decrease in that distress following surgery. Patients who are
      distressed have slightly worse pain preoperatively and for up to two years
      following knee arthroplasty as compared with patients with no psychological
      distress. With the exception of preoperative scores, these differences are not
      likely to be measurable at the individual patient level. WOMAC pain and function
      change scores do not differ between patients with and without distress after
      adjustment for covariates. LEVEL OF EVIDENCE: Prognostic Level I.

PMID- 17545418
TI  - Outcomes of posterior wall fractures of the acetabulum.
AB  - BACKGROUND: The Musculoskeletal Function Assessment (MFA) is a validated,
      reliable, self-administered questionnaire that is useful for determining
      functional status. The Merle d'Aubigne score is a clinical measure of hip
      function. The purpose of the present study was to evaluate the outcome
      information provided by these two instruments after operative treatment of
      elementary posterior wall fractures of the acetabulum. METHODS: Forty-six
      patients who had been followed for a minimum of two years after operative
      treatment of an elementary posterior wall fracture of the acetabulum were
      included in the study. Functional outcomes were assessed with use of the ten
      individual indices and total score of the MFA, and clinical outcomes were
      evaluated with use of the Merle d'Aubigne score. The MFA scores were compared
      with previously reported normative values and with previously reported values for
      similar patients with hip injuries. The duration of follow-up ranged from two to
      fourteen years (mean, five years). RESULTS: The mean Merle d'Aubigne score was 17
      (standard deviation, 1; range, 14 to 18), indicating overall good-to-excellent
      clinical results. However, the mean total MFA score was 23.17, which was
      significantly worse than the normative mean of 9.26 (p < 0.001). All MFA indices
      except hand/fine motor were similarly significantly worse than expected norms.
      The mean MFA total score was statistically similar to that reported by others for
      patients with hip injuries. The emotional category of the MFA score was found to
      be an important determinant of the total score. The Spearman rho correlation
      coefficient between the Merle d'Aubigne score and the MFA score was -0.62 (p <
      0.001). However, the Merle d'Aubigne score data were asymmetric, demonstrating a
      ceiling effect (crowding of the scores at the upper end of the scale, limiting
      the ability of the score to demonstrate differences between patients with
      supposedly better clinical outcomes). CONCLUSIONS: The total MFA scores for
      patients with a posterior wall fracture of the acetabulum were significantly
      worse than normative reference values. Thus, complete recovery after a posterior
      wall fracture of the acetabulum is uncommon, with residual functional deficits
      involving wide-ranging aspects of everyday living that do not necessarily have an
      obvious direct connection to hip function. Although the modified Merle d'Aubigne
      score may be useful for evaluating isolated hip function in patients who have
      been treated for an acetabular fracture, its shortcomings limit its usefulness as
      a method for evaluating functional outcome in these patients. Research efforts
      should be directed toward the identification of the psychosocial and other
      underlying determinants of functional outcome and potential related treatment
      interventions.

PMID- 17545419
TI  - Radiographic evaluation of idiopathic clubfeet undergoing Ponseti treatment.
AB  - BACKGROUND: The Ponseti method for treatment of idiopathic clubfeet involves the
      use of serial casts, percutaneous Achilles tenotomy in most cases, and bracing
      with an abduction orthosis to prevent relapse. Although Ponseti recommended
      evaluation of the infant clubfoot strictly by palpation, many orthopaedic
      surgeons still rely on radiographs for decision-making during treatment. The aim
      of this study was to document with radiographs the effect of percutaneous
      Achilles tenotomy as described by Ponseti. METHODS: We conducted a study of
      idiopathic clubfeet treated, at two centers, with the Ponseti method, including
      percutaneous Achilles tenotomy. Cast treatment was started within three weeks
      after birth, and radiographs were made before and after the tenotomy. Lateral
      radiographs with the foot in maximal dorsiflexion at the ankle were made for all
      patients, and anteroposterior radiographs of the foot were made at one center.
      The lateral tibiocalcaneal angle, the anteroposterior talocalcaneal angle, and
      the lateral talocalcaneal angle were measured on the radiographs. Foot
      dorsiflexion at the ankle was evaluated clinically. The results from both centers
      were evaluated separately and in combination. RESULTS: Lateral dorsiflexion
      radiographs that showed the foot and ankle were evaluated for eighty-seven
      clubfeet, and anteroposterior radiographs that showed the foot were evaluated for
      sixty-five clubfeet. The mean improvement in the lateral tibiocalcaneal angle
      after the tenotomy was 16.9 degrees . The mean change in the anteroposterior
      talocalcaneal angle was 2.1 degrees , and the mean change in the lateral
      talocalcaneal angle change was 1.4 degrees . The mean increase in clinically
      measured dorsiflexion after the tenotomy (in sixty-five feet) was 15.1 degrees .
      Only the lateral tibiocalcaneal angle and dorsiflexion as measured clinically
      changed significantly after the Achilles tenotomy (p < 0.05). When the results at
      each center were analyzed separately, they were found to be nearly identical.
      CONCLUSIONS: The increase in the lateral tibiocalcaneal angle after Achilles
      tenotomy is essentially the same as the increase in ankle dorsiflexion seen on
      clinical examination. The anteroposterior and lateral talocalcaneal angles are
      not influenced significantly by the tenotomy. Radiographs confirmed that the
      additional dorsiflexion obtained from the percutaneous Achilles tenotomy is true
      dorsiflexion occurring in the ankle and hindfoot and not in the midfoot. LEVEL OF
      EVIDENCE: Therapeutic Level IV.

PMID- 17545420
TI  - Structural integrity and clinical outcomes after arthroscopic repair of isolated
      subscapularis tears.
AB  - BACKGROUND: Isolated tears of the subscapularis occur less commonly than those
      involving the superior and posterior components of the rotator cuff. The purpose
      of the present study was to evaluate the structural integrity and clinical
      outcomes after arthroscopic repair of isolated subscapularis tears. METHODS: A
      prospective study of seventeen consecutive patients who were managed with an all
      arthroscopic repair of the subscapularis tendon was performed. The study group
      included thirteen men and four women who had an average age of forty-seven years
      at the time of surgery. The average interval from the onset of symptoms to the
      time of surgery was twenty-four months. Thirteen tears were traumatic, and four
      were degenerative. Seven patients had a tear involving the superior third of the
      tendon, six had a tear involving the superior two-thirds of the tendon, and four
      had complete separation of the subscapularis from its insertion on the lesser
      tuberosity. Clinical findings were assessed for all patients preoperatively and
      postoperatively with use of the Constant and University of California at Los
      Angeles scoring systems, and all patients had postoperative computed tomographic
      arthrography studies to evaluate the structural integrity of the repair. RESULTS:
      The average duration of follow-up was twenty-nine months. When the preoperative
      findings were compared with the most recent findings, the average relative
      Constant score had improved from 58% to 96% (p < 0.05), the average University of
      California at Los Angeles score had improved from 16 to 32 points (p < 0.05), the
      average pain score had improved from 5.9 to 13.5 points (p < 0.05), the average
      forward flexion had improved from 146 degrees to 175 degrees (p < 0.05), the
      average external rotation had improved from 50 degrees to 60.3 degrees (p <
      0.05), the average internal rotation had improved from the level of the sacrum to
      L1-L2 (p < 0.05), and the average abduction strength had improved from 7.4 to
      15.6 points (p < 0.05). The structural integrity of the repair was completely
      intact in fifteen patients and was partially reruptured in two patients on the
      basis of computed tomographic arthrography. Progression of fatty infiltration of
      the subscapularis was not observed in any patient. Subjectively, twelve patients
      were very satisfied with the result, four were satisfied, and one was not
      satisfied. CONCLUSIONS: Arthroscopic repair of an isolated subscapularis tear can
      yield marked improvements in shoulder function, can significantly reduce pain,
      and can result in a durable structural repair. LEVEL OF EVIDENCE: Therapeutic
      Level IV.

PMID- 17545421
TI  - Current practices of AAHKS members in the treatment of adult osteonecrosis of the
      femoral head.
AB  - BACKGROUND: There is currently no standardized protocol for evaluating and
      treating osteonecrosis of the femoral head in adults in the United States. We
      sought to understand current treatment practices of a group of surgeons who
      commonly treat this disease to determine if there was agreement on some aspects
      of care. METHODS: We designed a two-staged mixed-mode (mailed and faxed) sixteen
      question self-administered descriptive survey questionnaire to be sent to all 753
      active members of the American Association of Hip and Knee Surgeons (AAHKS). The
      survey design was based on Dillman's survey research methodology, and the
      questionnaire included hypothetical clinical scenarios based on the Steinberg
      classification system. The responses elucidated the opinions and treatment
      preferences of high-volume arthroplasty surgeons who treat adult patients with
      osteonecrosis of the femoral head. RESULTS: Of the 753 active members of the
      AAHKS, 403 (54%) responded to the questionnaire. Total hip replacement was
      reported to be the most frequent intervention for treatment of postcollapse
      (Steinberg stage-IIIB, IVB, V, and VI) osteonecrosis; core decompression was
      reported to be the most commonly offered intervention for symptomatic,
      precollapse (Steinberg stage-IB and IIB) osteonecrosis. Less frequently offered
      treatments included nonoperative management, osteotomy, vascularized and non
      vascularized bone-grafting, hemiarthroplasty, and arthrodesis. CONCLUSIONS: The
      care of adults with osteonecrosis of the femoral head varies among American
      orthopaedic surgeons specializing in hip and knee surgery. A consensus may evolve
      with a continued concerted effort on the part of interested surgeons, but it will
      require randomized, controlled, prospective studies of treatment of each stage of
      the disease and collaborative multicenter studies. LEVEL OF EVIDENCE: Therapeutic
      Level V.

PMID- 17545422
TI  - Classification, treatment, and outcome of osteochondritis dissecans of the
      humeral capitellum.
AB  - BACKGROUND: Indications for the treatment of osteochondritis dissecans of the
      humeral capitellum have remained unclear. The aims of this study were to analyze
      the outcomes and to determine the most useful classification for the choice of
      treatment. METHODS: The cases of 106 patients with osteochondritis dissecans of
      the capitellum were studied retrospectively. At the time of the initial
      presentation, the mean age of the patients was 15.3 years. The capitellar growth
      plate was open in eighteen patients and closed in eighty-eight. Thirty-six
      patients were treated nonoperatively. Fifty-five patients underwent fragment
      removal alone, twelve underwent fragment fixation with a bone graft, and three
      underwent reconstruction of the articular surface with use of osteochondral plug
      grafts from the lateral femoral condyle. The mean follow-up period was 7.2 years.
      The outcomes in terms of pain in the elbow, return to sports, and radiographic
      findings were analyzed and compared. RESULTS: An osteochondritis dissecans lesion
      with an open capitellar physis and a good range of elbow motion resulted in a
      good outcome. Continued elbow stress resulted in the worst outcome in terms of
      pain and radiographic findings. In patients with a closed capitellar physis,
      surgery provided significantly better results than elbow rest (p < 0.01).
      Fragment fixation or reconstruction provided significantly better results than
      fragment removal alone (p < 0.05). The results of removal alone were dependent on
      the size of the defect in the capitellum. The outcome in terms of pain was
      closely associated with sports activity and radiographic findings. CONCLUSIONS:
      We believe that osteochondritis dissecans of the capitellum can be classified as
      stable or unstable. Stable lesions that healed completely with elbow rest had all
      of the following findings at the time of the initial presentation: an open
      capitellar growth plate, localized flattening or radiolucency of the subchondral
      bone, and good elbow motion. Unstable lesions, for which surgery provided
      significantly better results, had one of the following findings: a capitellum
      with a closed growth plate, fragmentation, or restriction of elbow motion of > or
      =20 degrees . For large unstable lesions, fragment fixation or reconstruction of
      the articular surface leads to better results than simple excision. LEVEL OF
      EVIDENCE: Prognostic Level II.

PMID- 17545423
TI  - Functional outcomes after total claviculectomy as a salvage procedure. A series
      of six cases.
AB  - BACKGROUND: Total claviculectomy has been used for the treatment of tumor,
      infection, nonunion, and vascular compromise. Given its limited indications, few
      reports on the outcome after claviculectomy exist. The purpose of the present
      study was to evaluate the function of the shoulder, with use of a modern scoring
      system, after total claviculectomy. METHODS: A retrospective review of the
      records of six patients who had undergone unilateral claviculectomy was performed
      after an average duration of follow-up of 5.7 years. The indication for surgery
      had been an infection at the site of a clavicular nonunion for three patients,
      nonunion with subclavian vein compression for two, and pain after a failed medial
      clavicular excision for one. The preoperative and postoperative evaluations
      included testing of the range of motion, strength, and stability as well as
      determination of the American Shoulder and Elbow Surgeons score on the basis of a
      functional questionnaire. RESULTS: Range of motion was improved slightly or
      unchanged following claviculectomy. The mean American Shoulder and Elbow Surgeons
      score improved from 18 (range, 5 to 35) preoperatively to 88 (range, 75 to 95)
      postoperatively. The mean pain level (with 0 indicating no pain and 10 indicating
      the worst pain) decreased from 9.5 preoperatively to 1.5 postoperatively.
      Postoperatively, strength testing showed improvement from grade 4- (of 5) to 5 in
      all planes tested except extension (in which it remained at grade 4). Patient
      satisfaction was high, with a mean of 9.0 on a 10-point scale. There were five
      complications, including one subclavian vein laceration requiring vascular
      repair, two deep infections, and two superficial infections. CONCLUSIONS: Despite
      a high complication rate, the functional outcomes following claviculectomy were
      good in this group of six patients. Total claviculectomy may be a useful salvage
      procedure for clinical situations in which the restoration of normal clavicular
      osseous anatomy is impossible. Patients can expect acceptable pain relief and few
      or no deficits in activities of daily living. LEVEL OF EVIDENCE: Therapeutic
      Level IV.

PMID- 17545424
TI  - Safety of simultaneous bilateral total knee arthroplasty. A meta-analysis.
AB  - BACKGROUND: The safety of simultaneous bilateral total knee replacement remains
      controversial. Some studies have demonstrated a higher rate of serious
      complications, including death, following bilateral procedures, whereas others
      have suggested no increase in the complication rate. The objective of this meta
      analysis was to compare the safety of simultaneous bilateral total knee
      replacement with that of staged bilateral and unilateral total knee replacements.
      METHODS: A computerized literature search was conducted to identify all
      citations, from 1966 to 2005, concerning bilateral total knee replacement. All of
      the English-language abstracts were obtained. A multistage assessment was then
      performed to identify articles fulfilling the inclusion criteria for the study.
      All randomized, prospective studies reporting the outcome of bilateral total knee
      replacement were included. The details of the reported data were extracted, and
      an extensive analysis of relevant variables was carried out. RESULTS: One hundred
      and fifty published articles were identified, and eighteen that included a total
      of 27,807 patients (44,684 knees) were included in the meta-analysis. There were
      10,930 unilateral total knee replacements, 16,419 simultaneous bilateral total
      knee replacements, and 458 staged bilateral total knee replacements with at least
      three months between the operative procedures. The prevalences of pulmonary
      embolism (odds ratio = 1.8), cardiac complications (odds ratio = 2.49), and
      mortality (odds ratio = 2.2) were higher after simultaneous bilateral total knee
      replacement. The prevalence of deep venous thrombosis was lower after
      simultaneous bilateral total knee replacement, but this difference was not
      significant. The complication rates after the staged bilateral total knee
      replacements were similar to those in the patients who had undergone unilateral
      total knee replacement only. CONCLUSIONS: Compared with staged bilateral or
      unilateral total knee replacement, simultaneous bilateral total knee replacement
      carries a higher risk of serious cardiac complications, pulmonary complications,
      and mortality. The period of time between staged procedures that would eliminate
      these increased risks could not be determined from this study. LEVEL OF EVIDENCE:
      Therapeutic Level III.

PMID- 17545425
TI  - Two-stage reimplantation for periprosthetic knee infection involving resistant
      organisms.
AB  - BACKGROUND: Two-stage reimplantation is the most accepted mode of treatment for
      patients with a periprosthetic infection following total knee arthroplasty. Most
      studies, however, do not stratify their results on the basis of the type of
      infecting organism. The purpose of this study was to determine the outcomes for
      patients who had two-stage reimplantation for the treatment of infection with a
      resistant organism, methicillin-resistant Staphylococcus aureus or methicillin
      resistant Staphylococcus epidermidis, at the site of a total knee replacement.
      METHODS: A multicenter study was performed to review the cases of all patients
      treated between 1987 and 2003 because of an infection with methicillin-resistant
      Staphylococcus aureus or methicillin-resistant Staphylococcus epidermidis
      organisms at the site of a total knee replacement. The prevalence of reinfection
      following two-stage reimplantation was determined. Variables that may influence
      the outcome, such as the duration and type of intravenous antibiotics
      administered, previous surgery, and comorbidities of the host, were analyzed.
      RESULTS: We identified thirty-seven patients who had an infection with a
      resistant organism. All patients had negative cultures at the time of
      reimplantation. Four of the thirty-seven patients had a reinfection with the same
      organism, while five had a reinfection with a different organism. None of the
      variables noted above were found to be significantly associated with reinfection,
      on the basis of the numbers available. CONCLUSIONS: Reports in the literature
      have discouraged reimplantation for the treatment of an infection with a
      resistant organism at the site of a total knee replacement. While 24% of the
      patients in this series had a reinfection, 14% had a reinfection with a different
      organism. We believe that two-stage reimplantation remains a viable treatment
      option for patients who have an infection with a resistant organism at the site
      of a total knee replacement. LEVEL OF EVIDENCE: Therapeutic Level IV.

PMID- 17545426
TI  - Usefulness of histological analysis for predicting the presence of microorganisms
      at the time of reimplantation after hip resection arthroplasty for the treatment
      of infection.
AB  - BACKGROUND: Appropriate interpretation of a frozen section has a relatively high
      specificity and sensitivity for the diagnosis of infection when septic loosening
      of a prosthesis is suspected. However, its usefulness for predicting the presence
      of microorganisms at the time of reimplantation after hip resection arthroplasty
      for the treatment of infection is not well defined. The aim of the present study
      was to evaluate the usefulness of histological analysis in this situation.
      METHODS: From January 2002 to February 2006, a total of twenty-one patients
      underwent reimplantation after hip resection arthroplasty for the treatment of
      infection. Histological studies and cultures of specimens of periprosthetic
      tissue that had been obtained at the time of reimplantation were retrospectively
      reviewed. The results of culture were considered positive when the same
      microorganism was isolated in at least two samples. Two histological criteria
      were used to diagnose infection: (1) Criterion A (the Feldman criterion), defined
      as the presence of at least five neutrophils per high-power field (x400) in at
      least five separate microscopic fields and (2) Criterion B (the Athanasou
      criterion), defined as the presence of at least one neutrophil per high-power
      field (x400), on average, after examination of ten microscopic fields. The
      sensitivity, specificity, positive predictive value, and negative predictive
      value of each of these criteria were calculated with use of microbiological
      results as the gold standard for defining infection. RESULTS: Seven of the twenty
      one patients had a positive result on culture, and the most common microorganism
      was coagulase-negative staphylococcus. The sensitivity, specificity, positive
      predictive value, and negative predictive value of frozen-section analysis were
      28.5%, 100%, 100%, and 73.6%, respectively, according to the Feldman criterion
      and 71.4%, 64.2%, 50%, and 81.8%, respectively, according to the Athanasou
      criterion. The numbers of lymphocytes and plasma cells did not help in the
      diagnosis of infection. Fibrosis was more common in patients without an
      infection. CONCLUSIONS: The probability of infection is high when at least five
      neutrophils per high-power field are found in the periprosthetic tissue, but it
      is not possible to rule out infection when the number of neutrophils is less than
      five. LEVEL OF EVIDENCE: Diagnostic Level I.

PMID- 17545427
TI  - Tumor location affects the results of simple excision for multiple
      osteochondromas in the forearm.
AB  - BACKGROUND: The effectiveness of excision of osteochondromas in controlling the
      progression of forearm and wrist deformity remains an issue of controversy. The
      purpose of this study was to analyze the effectiveness of tumor excision in the
      correction of forearm and wrist deformity due to multiple osteochondromas in
      children, with an interpretation of the results based on different patterns of
      deformity. METHODS: Fourteen forearms in thirteen children with a follow-up of
      more than twenty-four months (average, fifty-three months) were included in the
      study. The forearms were divided into two groups on the basis of the location of
      the tumor and the pattern of deformity. In Group 1 (six forearms), the
      osteochondroma was only in the distal aspect of the ulna and caused compression
      of the radius. In Group 2 (eight forearms), tumors were in both the distal aspect
      of the ulna and the ulnar side of the distal part of the radius and were in
      contact with each other. Radial length, ulnar shortening, radial bowing, the
      radial articular angle, and carpal slip were measured as radiographic parameters.
      Ulnar shortening and radial bowing were expressed as a percentage of the radial
      length to make it possible to compare data between the individuals. Each
      parameter was evaluated before surgery and at the time of final follow-up.
      RESULTS: In Group 1, the percentage of ulnar shortening and the percentage of
      radial bowing had improved at the time of final follow-up; however, in Group 2,
      both the radial articular angle and the percentage of radial bowing had
      deteriorated significantly after the tumor excision (p = 0.049 and p = 0.017,
      respectively), even though the percentage of ulnar shortening showed no change.
      CONCLUSIONS: The effectiveness of simple excision of osteochondromas of the
      distal aspect of the forearm is influenced by the tumor location and is related
      to the pattern of the deformity. Simple tumor excision can correct the forearm
      deformity in patients with an isolated tumor of the distal part of the ulna.
      Conversely, in patients with tumors involving the distal part of the ulna and the
      ulnar side of the distal end of the radius, tumor excision alone is a less
      promising procedure for the correction of the deformity. LEVEL OF EVIDENCE:
      Prognostic Level IV.

PMID- 17545428
TI  - Arthroscopic rotator cuff repair with double-row fixation.
AB  - BACKGROUND: The treatment of rotator cuff tears has evolved from open surgical
      repairs to complete arthroscopic repairs over the past two decades. In this
      study, we reviewed the results of arthroscopic rotator cuff repairs with the so
      called double-row, or footprint, reconstruction technique. METHODS: Between 1998
      and 2002, 264 patients underwent an arthroscopic rotator cuff repair with double
      row fixation. The average age at the time of the operation was fifty-nine years.
      Two hundred and thirty-eight patients (242 shoulders) were available for follow
      up; 210 were evaluated with a full clinical examination and thirty-two, with a
      questionnaire only. Preoperative and postoperative examinations consisted of
      determination of a Constant score and a visual analogue score for pain as well as
      a full physical examination of the shoulder. Ultrasonography was done at a
      minimum of twelve months postoperatively to assess the integrity of the cuff.
      RESULTS: The average score for pain improved from 7.4 points (range, 3 to 10
      points) preoperatively to 0.7 point (range, 0 to 3 points) postoperatively. The
      subjective outcome was excellent or good in 220 (90.9%) of the 242 shoulders. The
      average increase in the Constant score after the operation was 25.4 points
      (range, 0 to 57 points). Ultrasonography demonstrated an intact rotator cuff in
      83% (174) of the shoulders overall, 47% (fifteen) of the thirty-two with a repair
      of a massive tear, 78% (thirty-two) of the forty-one with a repair of a large
      tear, 93% (113) of the 121 with a repair of a medium tear, and 88% (fourteen) of
      the sixteen with a repair of a small tear. Strength and active elevation
      increased significantly more in the group with an intact repair at the time of
      follow-up than in the group with a failed repair; however, there was no
      difference in the pain scores. CONCLUSIONS: Arthroscopic rotator cuff repair with
      double-row fixation can achieve a high percentage of excellent subjective and
      objective results. Integrity of the repair can be expected in the majority of
      shoulders treated for a large, medium, or small tear, and the strength and range
      of motion provided by an intact repair are significantly better than those
      following a failed repair. LEVEL OF EVIDENCE: Therapeutic Level IV.

PMID- 17545429
TI  - Late-presenting developmental dysplasia of the hip treated with the modified
      Hoffmann-Daimler functional method.
AB  - BACKGROUND: The general consensus is that nonoperative treatment of developmental
      dysplasia of the hip should not be attempted for patients in whom previous
      treatment of the disease has failed, those in whom the disease was neglected, or
      those in whom the disease presented late. In such cases, it is believed that the
      optimum period for hip remodeling has passed and that operative methods are
      preferable. The purpose of the present study was to report the efficacy of a
      modified form of the Hoffmann-Daimler method for the treatment of late-presenting
      developmental dysplasia of the hip. MATERIALS: We retrospectively reviewed the
      records of sixty-nine patients (ninety-five hips) with neglected developmental
      dysplasia of the hip who had been managed nonoperatively with a modification of
      the Hoffmann-Daimler method from 1971 to 2000. With this method, the patient
      wears a flexion harness (Phase A), during which time the femoral head is
      gradually reduced, followed by an abduction splint (Phase B), during which time
      the reduced hip remodels. We have modified the original method by introducing new
      treatment strategies. The study group included nine boys and sixty girls. The
      average age of the patients was sixteen months (range, six to forty-four months)
      at the start of treatment and 11.5 years (range, six to twenty-nine years) at the
      time of the latest follow-up. Radiographs were assessed to determine the
      acetabular index, the Severin classification, and the presence of evidence of
      osteonecrosis of the proximal femoral epiphysis. Hips that were rated as Severin
      class I or class II were classified as satisfactory, whereas those that were
      rated as Severin class III or class IV were classified as unsatisfactory.
      RESULTS: On the basis of the most recent follow-up radiographs, eighty-eight
      (93%) of the dislocated hips were classified as satisfactory (sixty-seven were
      rated as Severin class I and twenty-one were rated as Severin class II) and seven
      were classified as unsatisfactory (six were rated as Severin class III and one
      was rated as Severin class IV). No hip was rated as Severin class V or VI. The
      average acetabular index was 40 degrees +/- 7.4 degrees prior to the onset of
      treatment and 24 degrees +/- 5.7 degrees at the end of treatment. No
      redislocations or other complications were noted. Osteonecrosis was noted in six
      of the ninety-five hips. CONCLUSIONS: Late-presenting or neglected developmental
      dysplasia of the hip can be successfully treated with use of a modified Hoffmann
      Daimler method. The high rate of successful reduction, the low prevalence of
      osteonecrosis and residual dysplasia, and the limited complications may make this
      modified method a safe alternative to surgical treatment. LEVEL OF EVIDENCE:
      Therapeutic Level IV.

PMID- 17545430
TI  - Total elbow prosthesis loosening caused by ulnar component pistoning.
AB  - BACKGROUND: Linked semiconstrained total elbow prostheses have been used
      successfully but may be at higher risk for implant loosening than unlinked
      implants are. The purpose of the present report was to describe a previously
      unreported and potentially preventable cause of mechanical loosening of the ulnar
      component of a linked total elbow prosthesis. METHODS: A series of ten patients
      who had painful pistoning of the polymethylmethacrylate-coated ulnar component of
      a Coonrad-Morrey linked total elbow prosthesis were evaluated clinically and
      radiographically. RESULTS: All ten patients complained of elbow pain, and eight
      had a distinct sensation of the ulnar component moving within the ulna. Six
      patients either complained of squeaking within the elbow or could demonstrate
      squeaking on examination. Four patients had a complete radiolucent line around
      the ulnar component or the cement mantle, and six had an incomplete line around
      the ulnar component. Six patients had a radiolucent gap between the cement and
      the tip of the ulnar prosthesis. Two patients had proximal migration of the ulnar
      component within the cement mantle on lateral flexion radiographs. Three patients
      had anterior impingement, such as between the anterior flange of the humeral
      implant and a prominent coronoid process, on lateral flexion radiographs. At the
      time of revision arthroplasty, all ten patients were found to have a loose ulnar
      component, which was successfully revised with or without impaction grafting. At
      the time of the most recent follow-up, nine of the ten ulnar components were
      intact and stable. Three patients required an additional reoperation: one
      required triceps repair, one required revision of a loose humeral component, and
      one required a revision total elbow arthroplasty. CONCLUSIONS: Pistoning of the
      ulnar component in the cement mantle leading to failure by means of a pullout
      mechanism can occur in association with the Coonrad-Morrey total elbow prosthesis
      with a polymethylmethacrylate-precoated ulnar component. To prevent this problem
      following any total elbow arthroplasty, the surgeon should check for anterior
      impingement intraoperatively by ensuring that there is no contact between the
      anterior flange and a prominent coronoid process or the cement and that no
      distraction of the trial ulnar component from the ulna occurs with passive elbow
      flexion. This condition also can be avoided by ensuring that the ulnar component
      is not inserted too far distally. This mechanism of failure should be considered
      when future total elbow arthroplasty implants are designed. LEVEL OF EVIDENCE:
      Therapeutic Level IV.

PMID- 17545431
TI  - Correlation of body mass index and radiographic deformities in children with
      Blount disease.
AB  - BACKGROUND: Children with Blount disease tend to be heavier than their peers;
      however, the relationship between the magnitude of obesity and the severity of
      limb deformities in Blount disease has not been well studied. METHODS: A
      retrospective review of the preoperative medical records and radiographs of
      patients with previously untreated Blount disease was conducted. Demographic
      information including gender, ethnicity, the age when deformity was first noted,
      the age at the examination, and the body mass index was recorded. Frontal and
      sagittal plane deformities were analyzed by one examiner using full-length
      standing radiographs. The association of body mass index with various demographic
      and deformity parameters was then analyzed. RESULTS: Over an eight-year period,
      forty-five patients with sixty-five limbs affected by Blount disease were
      identified. Seventeen children (twenty-seven limbs) had early-onset Blount
      disease, and twenty-eight children (thirty-eight limbs) had late-onset disease.
      Fifteen of the children with early-onset disease and twenty-six of those with
      late-onset disease were overweight. There was no significant relationship between
      body mass index and gender, ethnicity, or laterality. The children with early
      onset disease tended to have a lower body mass index but a greater magnitude of
      radiographic deformities compared with the children with late-onset disease.
      Greater varus malalignment (r = 0.74, p < 0.0001) and tibial procurvatum (r = 
      0.79, p = 0.002) were noted with an increasing body mass index in the early
      onset, but not the late-onset, group of patients. Irrespective of the age at
      onset, the correlation of body mass index with frontal and sagittal plane
      deformities was stronger in extremely obese children (body mass index of > or
      =40). CONCLUSIONS: There is a significant relationship between the magnitude of
      obesity and biplanar radiographic deformities in children with the early-onset
      form of Blount disease and in those with a body mass index of > or =40. These
      clinical findings are consistent with the literature concerning the effect of
      compressive forces on growth at the proximal tibial physis. LEVEL OF EVIDENCE:
      Prognostic Level II.

PMID- 17545432
TI  - Self-assessed outcome at two to four years after shoulder hemiarthroplasty with
      concentric glenoid reaming.
AB  - BACKGROUND: Active and young individuals with glenohumeral arthritis who are
      treated with total glenohumeral arthroplasty are at risk for loosening or wear of
      the prosthetic glenoid component. This study tests the hypothesis that patients
      with severe glenohumeral arthritis have improvement in self-assessed shoulder
      comfort and function at two to four years after treatment with the combination of
      humeral hemiarthroplasty and concentric glenoid reaming without tissue or
      prosthetic component interposition. METHODS: Thirty-seven consecutive patients
      (thirty-eight shoulders), with a mean age of fifty-seven years, who were managed
      by one surgeon were enrolled in this prospective study. The procedure consisted
      of an uncemented humeral hemiarthroplasty combined with reaming of the glenoid to
      a diameter 2 mm larger than that of the prosthetic humeral head. The duration of
      follow-up ranged from two to four years (average, 2.7 years) for thirty-five
      shoulders. Self-assessed comfort and function was documented with use of the
      Simple Shoulder Test, and radiographs were evaluated. RESULTS: Thirty-two
      shoulders demonstrated improved comfort and function according to patient self
      assessment, one demonstrated no change, and two had worse function following the
      procedure. The total number of Simple Shoulder Test functions that could be
      performed increased from 4.7 (of a possible 12.0) before surgery to 9.4 at the
      time of the final follow-up. The patients demonstrated significant improvement in
      ten of the twelve individual functions of the Simple Shoulder Test (p < 0.022 to
      p < 0.00001). With the numbers studied, gender, diagnosis, age, glenoid wear, and
      preoperative glenoid erosion did not significantly affect final shoulder function
      or overall improvement. The range of motion was significantly improved for all
      individuals (p < 0.00001). Radiographically, twenty-two patients had a joint
      space between the glenoid bone and the humeral prosthesis at the time of final
      follow-up. These shoulders had significantly better function than those without a
      preserved joint space (p < 0.017). There were no surgical complications and no
      revisions to total shoulder arthroplasty. CONCLUSIONS: At a minimum follow-up of
      two years, a selected series of patients who had humeral hemiarthroplasty with
      concentric glenoid reaming for the treatment of glenohumeral arthritis showed
      significant improvement in self-assessed shoulder comfort and function. Further
      study, however, is needed before routine application of this procedure can be
      recommended. LEVEL OF EVIDENCE: Therapeutic Level IV.

PMID- 17545433
TI  - Brachialis muscle anatomy. A study in cadavers.
AB  - BACKGROUND: There have been conflicting descriptions of brachialis muscle anatomy
      in the literature. The purpose of the present study was to clarify brachialis
      muscle anatomy in order to refine surgical techniques around the elbow. METHODS:
      Eleven cadaveric upper limbs were dissected under loupe magnification. The gross
      morphological characteristics, relationships, and nerve supply of the brachialis
      muscle were recorded. The nerve supply was examined histologically to confirm the
      gross findings. RESULTS: In all specimens, the brachialis muscle had two heads.
      The larger, superficial head originated from the anterolateral aspect of the
      humerus, proximal to the smaller, deep head. The superficial head contained
      longitudinal fibers, which inserted by means of a thick round tendon onto the
      ulnar tuberosity. The deep head fibers were fan-shaped and converged to insert by
      means of an aponeurosis onto the coronoid process. In all specimens, a branch of
      the radial nerve supplied the inferolateral fibers of the deep head. CONCLUSIONS:
      Our observations of brachialis muscle anatomy differ considerably from the
      descriptions in the current literature. The larger, superficial head has the
      mechanical advantage of a more proximal origin and a more distal insertion, which
      may enable it to provide the bulk of flexion strength. The smaller, oblique, deep
      head has a more anterior insertion on the coronoid, which may facilitate the
      initiation of elbow flexion from full extension. The radial nerve-innervated
      inferolateral fibers of the deep head run in a direction similar to the anconeus
      muscle, forming a muscular sling around the elbow. This complex may act to
      dynamically stabilize the ulnohumeral joint. CLINICAL RELEVANCE: This information
      may enhance surgical techniques about the elbow. The identification of an
      internervous plane may allow for improvement in the current anterior and
      anterolateral surgical approaches to the humerus. The tendon of the superficial
      head is well positioned to allow its transfer to the radial tuberosity,
      potentially improving supination strength in the absence of a distal biceps
      tendon. It is possible that the tendon of the superficial head might also be used
      to reconstruct the anular ligament or the medial collateral ligament of the
      elbow.

PMID- 17545434
TI  - Identification of orthopaedic infections using broad-range polymerase chain
      reaction and reverse line blot hybridization.
AB  - BACKGROUND: Culture remains the gold standard in the diagnosis of bacterial
      infection, but molecular biological techniques have yielded promising results. In
      this study, we validated a combined polymerase chain reaction and reverse line
      blot hybridization protocol for identifying musculoskeletal infections. METHODS:
      Samples were obtained from seventy-six patients undergoing orthopaedic surgery
      for various aseptic and septic indications. The diagnosis of infection was based
      on a review of all available clinical and culture data. In addition to routine
      culture for aerobic and anaerobic growth, samples were analyzed with a broad
      range 16S rRNA polymerase chain reaction and subsequent reverse line blot
      hybridization with use of twenty-eight group, genus, and species-specific
      oligonucleotide probes. RESULTS: An infection was diagnosed on the basis of
      patient data in thirty-one patients. All but one of the patients with a clinical
      diagnosis of infection had a positive result of the polymerase chain reaction
      reverse line blot hybridization. Five of the forty-five patients in whom an
      infection was not suspected on the basis of patient data had at least one
      positive result of the polymerase chain reaction-reverse line blot hybridization.
      Cultures demonstrated microorganisms in twenty-five patients with an infection
      and in two patients in whom an infection was not suspected on the basis of the
      patient data. Staphylococcus aureus was the most common organism grown on
      culture. The species identified by the polymerase chain reaction-reverse line
      blot hybridization was in full accordance with that grown on culture in all but
      one patient. CONCLUSIONS: Polymerase chain reaction-reverse line blot
      hybridization performed well in detecting and identifying the various bacterial
      species and was more sensitive than routine culture. It identified Staphylococcus
      aureus as the most frequently found microorganism. Five patients in whom an
      infection was not suspected on the basis of the patient data had a positive
      result of the polymerase chain reaction, which may have been caused by
      contamination of the samples. However, three of these patients had aseptic
      loosening of a total hip prosthesis, suggesting the presence of a low-grade
      bacterial infection that remained undetected by the culture but was detected by
      the polymerase chain reaction-reverse line blot hybridization. LEVEL OF EVIDENCE:
      Diagnostic Level III.

PMID- 17545435
TI  - Factors associated with the loss of thickness of polyethylene tibial bearings
      after knee arthroplasty.
AB  - BACKGROUND: Wear of the polyethylene tibial bearing is a leading cause of failure
      of knee replacements done prior to the current decade. The objective of this
      study was to determine how patient-related factors, implant-related factors, and
      limb or tibial component alignment influenced the amount of thickness loss in
      polyethylene tibial bearings that were retrieved at the time of revision surgery
      or after the death of the patient. METHODS: We retrieved polyethylene tibial
      bearings from eighty-one unicondylar and eighty-nine total knee replacements that
      had been performed because of osteoarthritis with varus deformity from 1984 to
      1998. All of the polyethylene bearings had been sterilized with gamma radiation
      in air. Polyethylene loss was quantified as the change in the minimum bearing
      thickness per years in vivo (the mean time in vivo [and standard deviation] was 8
      +/- 4 years). Multiple linear regression was used to assess whether polyethylene
      loss was associated with age, weight, gender, varus angle of the tibial
      component, postoperative hip-knee-ankle angle, initial thickness of the
      polyethylene, shelf age of the polyethylene, and either the type of polyethylene
      (for total knee replacements, which were of one posterior cruciate ligament
      retaining design) or the manufacturer (for unicondylar knee replacements), and to
      determine the magnitude by which polyethylene loss would change if any of the
      significant risk factors were changed. RESULTS: The mean loss (and standard
      deviation) of polyethylene thickness in the medial compartment of total knee
      replacements (0.33 +/- 0.28 mm/yr) and that in medial unicompartmental knee
      replacements (0.49 +/- 0.40 mm/yr) were significantly (p < 0.05) associated with
      the same three variables: patient age, postoperative hip-knee-ankle angle, and
      shelf age of the polyethylene. A total knee bearing with a one-year increase in
      shelf age, a unicondylar knee bearing with a six-month increase in shelf age, a
      patient who was ten years younger at the time of operation, or a limb that was
      aligned in 5 degrees more varus (less valgus) had similar effects on the loss of
      polyethylene thickness in the medial compartment; the coefficients of the linear
      regression equations indicated that any one of these changes would increase
      polyethylene loss by 0.11 to 0.14 mm/yr. CONCLUSIONS: The wear-related loss of
      thickness in gamma-irradiated-in-air polyethylene bearings from unicondylar and
      total knee replacements implanted in osteoarthritic knees with varus deformity is
      influenced mainly by the shelf age of the polyethylene, the age of the patient,
      and the postoperative angulation of the knee in the coronal plane. CLINICAL
      RELEVANCE: Although polyethylene bearings have not been sterilized with gamma
      radiation in air since the end of the last decade, many arthroplasty patients
      have polyethylene bearings that were sterilized with use of this method. An
      understanding of the findings of this study may be of value as these patients
      return for follow-up care. Whether the study findings have relevance to bearings
      sterilized with other methods is unclear and will remain so for many years. LEVEL
      OF EVIDENCE: Prognostic Level II.

PMID- 17545436
TI  - BMP-14 gene therapy increases tendon tensile strength in a rat model of Achilles
      tendon injury.
AB  - BACKGROUND: Molecular and cellular-based enhancements of healing combined with
      conventional methods may yield better outcomes after the surgical management of
      tendon injury. We examined the histological and biomechanical effects of
      adenovirus-mediated transgene expression of bone morphogenetic protein-14 (BMP
      14) on healing in a rat Achilles tendon laceration model. Specifically, we
      hypothesized that this delivery system for gene therapy would hasten the
      restoration of the normal histological appearance and tensile strength of a
      surgically repaired tendon. METHODS: The right Achilles tendon of ninety male
      Sprague-Dawley rats was transected, repaired, and immediately infected with
      adenovirus expressing either the gene for green fluorescent protein (AdGFP) or
      the gene for human BMP-14 and green fluorescent protein (AdBMP-14). A sham
      control group received no viral-mediated infection after repair. Animals from
      each of the three groups were killed at one, two, and three weeks after surgery.
      The retrieved tendons were inspected, examined under light and fluorescent
      microscopy, and tested to determine their tensile strength. RESULTS: Tendons
      transduced with BMP-14 exhibited less visible gapping, a greater number of
      neotenocytes at the site of healing, and 70% greater tensile strength than did
      either those transduced with GFP or the sham controls at two weeks after repair.
      Histological examination revealed no inflammatory response to the adenovirus in
      tendons transduced with BMP-14 or GFP. No ectopic bone or cartilage formed in the
      tendons transduced with BMP-14. CONCLUSIONS: Adenovirus-mediated gene therapy
      with BMP-14 expedites tendon-healing in this animal model. No adverse
      immunological response to the adenoviral vector was detected in the host tissue,
      and the local production of BMP-14 did not induce unwelcome bone or cartilage
      formation within the healing tendon. CLINICAL RELEVANCE: The results of this
      animal study suggest that gene therapy with BMPs may improve the capacity of
      injured musculoskeletal tissue to heal.

PMID- 17545437
TI  - Malignant transformation of synovial chondromatosis of the shoulder to
      chondrosarcoma. A case report.

PMID- 17545438
TI  - Focal fibronodular heterotopic ossification. A case report.

PMID- 17545439
TI  - Atraumatic compartment syndrome: a manifestation of toxic shock and infectious
      pyomyositis in a child. A case report.

PMID- 17545440
TI  - Preventing the development of chronic pain after orthopaedic surgery with
      preventive multimodal analgesic techniques.
AB  - The prevalences of complex regional pain syndrome, phantom limb pain, chronic
      donor-site pain, and persistent pain following total joint arthroplasty are
      alarmingly high. Central nervous system plasticity that occurs in response to
      tissue injury may contribute to the development of persistent postoperative pain.
      Many researchers have focused on methods to prevent central neuroplastic changes
      from occurring through the utilization of preemptive or preventive multimodal
      analgesic techniques. Multimodal analgesia allows a reduction in the doses of
      individual drugs for postoperative pain and thus a lower prevalence of opioid
      related adverse events. The rationale for this strategy is the achievement of
      sufficient analgesia due to the additive effects of, or the synergistic effects
      between, different analgesics. Effective multimodal analgesic techniques include
      the use of nonsteroidal anti-inflammatory drugs, local anesthetics, alpha-2
      agonists, ketamine, alpha(2)-delta ligands, and opioids.

PMID- 17545441
TI  - The relevance of culturally competent care in orthopaedics to outcomes and health
      care disparities.

PMID- 17545442
TI  - Orthopaedic surgeons as educators. Applying the principles of adult education to
      teaching orthopaedic residents.

PMID- 17545443
TI  - Training resources in arthroscopic rotator cuff repair.
AB  - BACKGROUND: All-arthroscopic rotator cuff repair is becoming more commonly
      performed with recent improvements in implants, instrumentation, and techniques.
      This study evaluated the influence of different training resources for surgeons
      performing this procedure. METHODS: A twenty-eight-item survey was created to
      evaluate the methods by which orthopaedic surgeons are trained in the skill of
      all-arthroscopic rotator cuff repair. We selected 2455 surgeons from the American
      Academy of Orthopaedic Surgeons web site who indicated that they performed
      shoulder surgery, arthroscopic surgery, and/or sports medicine as part of their
      practice. Using a 5-point Likert scale, the respondents rated the relative
      importance of different training resources, including the completion of a sports
      medicine or shoulder surgery fellowship, attendance at instructional courses, and
      practice on shoulder models, in contributing to their ability to perform
      arthroscopic rotator cuff repair. RESULTS: Of the 2455 surveys sent, 1076 were
      returned (a response rate of 43.8%). Significantly more surgeons indicated that
      they performed arthroscopic repairs for a 2-cm tear compared with a 5-cm tear (p
      < 0.001). A younger age, higher volume of shoulder arthroscopies, and higher
      volume of rotator cuff repairs were all associated with significantly higher
      rates of preference for all-arthroscopic repairs compared with other types of
      repairs (p < 0.001). Compared with surgeons who received training in shoulder
      surgery during residency only, surgeons who had completed either shoulder or
      sports medicine fellowships were more likely to perform all-arthroscopic repairs.
      When ranking the relative importance of resources in the training for all
      arthroscopic repair, the overall Likert scale scores were highest for a sports
      medicine fellowship (3.49), hands-on instructional courses (3.33), and practice
      in an arthroscopy laboratory on cadaver specimens (3.22). Likert scores were
      lowest for residency training (2.02), practice on artificial shoulder models
      (2.13), and Internet resources (2.25). CONCLUSION: The information from this
      survey may be used to direct the continually evolving training of surgeons in
      arthroscopic rotator cuff repairs.

PMID- 17545444
TI  - What's new in musculoskeletal oncology.

PMID- 17545445
TI  - Geriatric psychiatry research in Australia.

PMID- 17545446
TI  - Prevalence of mental disorders in the elderly: the Australian National Mental
      Health and Well-Being Survey.
AB  - OBJECTIVE: To describe the 1- and 12-month prevalence of mental disorders, their
      demographic correlates, and their impact on service utilization and disability in
      individuals 65 years of age and over in a comprehensive epidemiological survey of
      mental health in Australia. METHODS: A noninstitutionalized national probability
      sample of elderly Australian residents was interviewed as part of the Australian
      National Mental Health and Well-being Survey (NMHWS). The prevalence of
      International Classification of Diseases, Tenth Revision and Diagnostic and
      Statistical Manual of Mental Disorders, Fourth Edition mental disorders was
      estimated from the Composite International Diagnostic Interview and other
      screening instruments. RESULTS: Of 1,792 elderly NMHWS respondents, 13% reported
      symptoms consistent with a mental disorder in the past 1 month, and 16% reported
      symptoms consistent with a mental disorder in the past 12 months. Women
      experienced higher rates of affective disorders and generalized anxiety disorder
      and had lower rates of substance abuse compared with men. After excluding
      cognitive disorder, increasing age was associated with less likelihood of having
      symptoms of any mental disorder. Older age and never having been married were
      associated with less likelihood of having symptoms of an affective disorder.
      Those with cognitive impairment were more likely to have had symptoms consistent
      with an affective disorder. Comorbidity was predictive of increasing disability
      on the 12-item Short Form but rates of mental health consultation were low, even
      for those with multiple disorders. CONCLUSION: Community-dwelling elderly
      Australians experience substantial rates of mental disorders. Demographic
      correlates of mental disorder in this elderly population appear to differ from
      those established in younger populations. Mental disorder in elderly Australians
      is associated with significant disability, but rates of specialist mental health
      consultation is low, even for those with multiple comorbidities. The reasons for
      this must be examined.

PMID- 17545447
TI  - Effects of sociodemographic and health variables on Mini-Mental State Exam scores
      in older Australians.
AB  - OBJECTIVE: This article examines the influence of sociodemographic, biological,
      and health variables on Mini-Mental State Exam (MMSE) performance, and assesses
      how the diversity of the population should be reflected in the MMSE cutoff scores
      used for screening. METHODS: The sociodemographic profiles and MMSE scores of
      adults aged 65-years and over who participated in the Australian National Mental
      Health and Well-being Survey were assessed (N = 1,792). RESULTS: The regression
      models showed that older age, education levels, language spoken at home and in
      country of birth, socioeconomic status (SES), occupation, sex, and presence of a
      mood disorder made significant and unique contributions to performance on the
      MMSE. The individual (univariate) influence of each factor ranged from -2.61 to
      0.09 points, with non-English speaking background (NESB) making the biggest
      impact. Based on a MMSE score of < or =23 points, 7.7% of the Australian elderly
      population screened positive for cognitive impairment that may be indicative of
      dementia. In those scoring < or =23 points, the multivariate model accounted for
      24.61% of the variance. CONCLUSION: Many sociodemographic variables and the
      presence of a mood disorder influence MMSE performance. Using conventional cutoff
      scores for screening will lead to a high rate of false positives in older adults
      (75+ years), those with NESB, and those with low SES, and is insensitive for
      those with high education. The authors suggest simple rules for the correction of
      the impact of these variables.

PMID- 17545448
TI  - Rates of depression at 3 and 15 months poststroke and their relationship with
      cognitive decline: the Sydney Stroke Study.
AB  - OBJECTIVE: To investigate the frequency and correlates of depression at 3 and 15
      months after stroke. METHODS: A total of 164 consecutive eligible stroke patients
      and 100 comparison subjects received extensive medical, psychiatric, and
      neuropsychological assessments; a subset also received magnetic resonance imaging
      scans. Comprehensive assessments included ratings for Diagnostic and Statistical
      Manual of Mental Disorders, Fourth Edition major or minor depression at 3-6
      months (index assessment) and 15 months (follow-up assessment) after stroke. The
      comparison subjects, who were similar in age and sex, were similarly assessed
      twice, 12 months apart. RESULTS: Major or minor depression was present in 12.0%
      of stroke patients at index assessment and in 20.7% at follow-up which included
      18 new cases (13.4%). By follow-up, stroke patients with depression had
      significantly greater impairment of functional ability and global cognition than
      nondepressed stroke patients or comparison subjects. Depression was not
      associated with age, intellectual decline prior to stroke or side or severity of
      stroke. Patients who experienced a TIA or stroke during the follow-up, who had
      developed dementia by three months or who were not living with a relative or
      partner were more likely to be depressed at follow-up. Dementia at 3 months
      predicted depression, but the reverse did not hold. CONCLUSION: Depression may be
      less frequent after stroke than previously reported and is related to cumulative
      vascular brain pathology rather than side and severity of single strokes.
      Clinicians should strive to slow the progression of cerebrovascular disease and
      encourage greater social support.

PMID- 17545449
TI  - Amygdala in stroke/transient ischemic attack patients and its relationship to
      cognitive impairment and psychopathology: the Sydney Stroke Study.
AB  - OBJECTIVE: To examine the structural abnormalities in the amygdala in stroke
      patients and see what contribution the amygdala may make to psychopathology and
      cognitive dysfunction related to stroke, because the amygdala has important roles
      in the processing of emotions, cognitive function, and psychiatric disorders.
      METHODS: The authors assessed 47 stroke/transient ischemic attack (TIA) patients
      3-6 months after the event and 54 comparison healthy subjects, using
      neuropsychological tests, medical and psychiatric examination and magnetic
      resonance imaging (MRI) brain scans. Volumetric T1-weighted MRI was used to
      obtain amygdala volumes by manual tracing. RESULTS: Stroke/TIA patients had
      smaller right amygdalar volume, more white matter hyperintensities (WMHs), and
      larger lateral ventricles. The amygdala was smaller in stroke/TIA patients with
      cognitive impairment compared to those without impairment. The right amygdala
      volume was negatively correlated with visual new learning and not related to
      depression, anxiety, irritability, agitation or apathy at baseline or 12-month
      follow-up. However, baseline amygdala volume was negatively correlated with
      Hamilton depression scores at 12 months in healthy comparison subjects.
      Hypertension and atrial fibrillation, and to a lesser extent WMHs, were
      predictors of amygdala volume. CONCLUSION: The amygdala is smaller in stroke/TIA
      patients, especially in those with cognitive impairment. This may partly be
      accounted for by hypertension, white matter lesions, and atrial fibrillation. It
      is not related to psychopathology except that small amygdalae may increase
      vulnerability to depression.

PMID- 17545450
TI  - Prevalence and risk factors for depression in a longitudinal, population-based
      study including individuals in the community and residential care.
AB  - OBJECTIVE: The authors report the population prevalence of depression in older
      adults living in the community and in residential care. Demographic, medical,
      health behavior, functional and cognitive measures, and transition to residential
      care are evaluated as risk factors for depression over eight years. METHODS:
      Depression prevalence estimates were obtained from the initial electoral role
      sample of the Australian Longitudinal Study of Ageing that included persons
      living in residential care. A subsample (N = 1,116) based on follow-up data were
      included in longitudinal multilevel analyses that evaluated between-person and
      within-person predictors associated with scores from the Center for Epidemiology
      Depression Scale. RESULTS: At wave 1, 14.4% of community-dwelling and 32.0% of
      residential care-dwelling participants were depressed (15.2% of total cases).
      Increase in depression was associated with antidepressant status, sex, education,
      and marital status, but not history of hypertension, stroke, diabetes, heart
      disease, or smoking. Time-varying predictors, including residential care,
      activities of daily living, instrumental activities of daily living, self-rated
      health, and Mini-Mental State Examination, predicted depressive symptoms both
      between and within persons. CONCLUSIONS: Depression is strongly linked with
      factors indicating increased dependency. Risk assessment and targeting of
      intervention strategies to prevent depression in late life should incorporate
      changes in functional capacity, mental status, and need for residential care.

PMID- 17545452
TI  - Unmet needs for services for older adults with mental illness: comparison of
      views of different stakeholder groups.
AB  - OBJECTIVE: The authors assessed the need for mental health services among older
      adults in San Diego County, California, by determining what needs were not being
      addressed by existing services, what services were necessary to address these
      needs, and how much consensus there was among different stakeholders with respect
      to the problems and solutions related to service delivery. METHODS:
      Semistructured interviews were conducted with 23 health care and social service
      providers and administrators, 16 services consumers and other older adults (55
      years of age and older), and 19 caregivers/family members and patient/client
      advocates. This was followed by four focus groups comprised of 18 providers and
      administrators, six focus groups comprised of 50 consumers and other older
      adults, and five focus groups comprised of 39 caregivers (family members and
      advocates). RESULTS: The unmet needs fell into three categories: mental health
      services, physical health services, and social services. Two interrelated themes
      were identified by participants: 1) the need for age-appropriate and culturally
      appropriate services to overcome barriers to mental health services access, use,
      and quality; and 2) the interrelations between unmet needs that address
      prevention as well as treatment of mental illness, including socialization and
      social support, transportation, housing, and physical health care. Differences in
      stakeholder assessment of unmet needs were associated with respective roles in
      delivery and use of mental health services. CONCLUSION: Age-appropriate and
      culturally appropriate solutions that address both prevention and treatment may
      represent the best strategies for addressing the challenges of mental illness and
      are most likely to be endorsed by all three groups of stakeholders.

PMID- 17545451
TI  - Late-life depressive symptoms are associated with both hyperactivity and
      hypoactivity of the hypothalamo-pituitary-adrenal axis.
AB  - OBJECTIVE: Although depression has been associated with hyperactivity of the
      hypothalamo-pituitary-adrenal (HPA) axis, recent studies among depressed elderly
      have found decreased cortisol levels, which may be due to underlying physical
      frailty associated with HPA-axis hypoactivity. The authors examined the
      relationship between urinary cortisol level and late-life depressive symptoms.
      The authors also explored whether hypo- and hypercortisolemic depressive symptoms
      are qualitatively different. METHODS: Data are from 881 community-dwelling
      participants, average age 74.2 years, of the Aging in the Chianti Area Study.
      Depressive symptoms were assessed using the Center for Epidemiologic Studies
      Depression Scale (CES-D) scale and cortisol levels were determined in 24-hour
      urine samples. RESULTS: Mean urinary cortisol level was 98.9 microg/24 hours
      (SD=47.8), and 31% of the sample had significant depressive symptoms (CES-D > or
      =16). There was no linear association between urinary cortisol level and
      depressive symptoms; however, there was a nonlinear association between urinary
      cortisol level and depressive symptoms. Older persons in the lowest and highest
      urinary cortisol deciles were 2.2 and 1.9 times more likely to have significant
      depressive symptoms than older persons in all other deciles. Depressed persons
      with low cortisol presented more physical frailty than depressed persons with
      high cortisol. CONCLUSION: Late-life depressive symptoms are associated with both
      hyperactivity and hypoactivity of the HPA axis, which suggests distinct
      mechanisms for these associations.

PMID- 17545453
TI  - Do cerebrovascular risk factors confer risk for suicide in later life? A case
      control study.
AB  - OBJECTIVE: Cerebrovascular pathologies have been implicated as a cause of
      depressive disorders. This study aims to examine the role of cerebrovascular risk
      factors in late-life suicide. METHODS: The authors calculated cerebrovascular
      risk factor (CVRF) score, based on the American Heart Association Criteria, for
      each case and comparison subject from a psychological autopsy study of suicide
      among community-dwelling adults over age 50 years. RESULTS: CVRF scores were
      significantly higher in suicide cases than community-dwelling comparison subjects
      after accounting for age, sex, depression diagnosis, and functional status.
      CONCLUSION: Cerebrovascular disease may predispose to suicide in older adults by
      a variety of psychopathological means.

PMID- 17545454
TI  - Chronic obstructive pulmonary disease and premature aging.

PMID- 17545455
TI  - Sickle cell disease-associated pulmonary hypertension: a coat of many colors.

PMID- 17545456
TI  - Obstructive sleep apnea and atherosclerosis: a new paradigm.

PMID- 17545457
TI  - Update in chronic obstructive pulmonary disease 2006.

PMID- 17545458
TI  - An official American Thoracic Society/European Respiratory Society statement:
      pulmonary function testing in preschool children.

PMID- 17545459
TI  - Circulating endothelial cells in obstructive sleep apnea: an important
      methodological lesson.

PMID- 17545460
TI  - Role of CD146 in detection of apoptotic circulating endothelial cells in
      obstructive sleep apnea.

PMID- 17545461
TI  - Avoiding mistakes in calculating the number needed to treat in severe COPD.

PMID- 17545462
TI  - Fishing for the origins of cancer.

PMID- 17545463
TI  - Translation factor control of ribosome conformation during start codon selection.

PMID- 17545464
TI  - Synchronicity: policing multiple aspects of gene expression by Ctk1.

PMID- 17545465
TI  - Advances in signaling in vertebrate regeneration as a prelude to regenerative
      medicine.
AB  - While all animals have evolved strategies to respond to injury and disease, their
      ability to functionally recover from loss of or damage to organs or appendages
      varies widely damage to skeletal muscle, but, unlike amphibians and fish, they
      fail to regenerate heart, lens, retina, or appendages. The relatively young field
      of regenerative medicine strives to develop therapies aimed at improving
      regenerative processes in humans and is predicated on >40 years of success with
      bone marrow transplants. Further progress will be accelerated by implementing
      knowledge about the molecular mechanisms that regulate regenerative processes in
      model organisms that naturally possess the ability to regenerate organs and/or
      appendages. In this review we summarize the current knowledge about the signaling
      pathways that regulate regeneration of amphibian and fish appendages, fish heart,
      and mammalian liver and skeletal muscle. While the cellular mechanisms and the
      cell types involved in regeneration of these systems vary widely, it is evident
      that shared signals are involved in tissue regeneration. Signals provided by the
      immune system appear to act as triggers of many regenerative processes.
      Subsequently, pathways that are best known for their importance in regulating
      embryonic development, in particular fibroblast growth factor (FGF) and Wnt/beta
      catenin signaling (as well as others), are required for progenitor cell formation
      or activation and for cell proliferation and specification leading to tissue
      regrowth. Experimental activation of these pathways or interference with signals
      that inhibit regenerative processes can augment or even trigger regeneration in
      certain contexts.

PMID- 17545466
TI  - Crystal structure of the human GINS complex.
AB  - The GINS complex mediates the assembly of the MCM2-7 (minichromosome maintenance)
      complex with proteins in a replisome progression complex. The eukaryotic GINS
      complex is composed of Sld5, Psf1, Psf2, and Psf3, which must be assembled for
      cell proliferation. We determined the crystal structure of the human GINS
      complex: GINS forms an elliptical shape with a small central channel. The
      structures of Sld5 and Psf2 resemble those of Psf1 and Psf3, respectively. In
      addition, the N-terminal and C-terminal domains of Sld5/Psf1 are permuted in
      Psf2/Psf3, which suggests that the four proteins have evolved from a common
      ancestor. Using a structure-based mutational analysis, we identified the
      functionally critical surface regions of the GINS complex.

PMID- 17545467
TI  - Notch activation stimulates transient and selective binding of Su(H)/CSL to
      target enhancers.
AB  - The CSL [CBF1/Su(H)/Lag2] proteins [Su(H) in Drosophila] are implicated in
      repression and activation of Notch target loci. Prevailing models imply a static
      association of these DNA-binding transcription factors with their target
      enhancers. Our analysis of Su(H) binding and chromatin-associated features at 11
      E(spl) Notch target genes before and after Notch revealed large differences in
      Su(H) occupancy at target loci that correlated with the presence of polymerase II
      and other marks of transcriptional activity. Unexpectedly, Su(H) occupancy was
      significantly and transiently increased following Notch activation, suggesting a
      more dynamic interaction with targets than hitherto proposed.

PMID- 17545468
TI  - Staphylococcus aureus RNAIII coordinately represses the synthesis of virulence
      factors and the transcription regulator Rot by an antisense mechanism.
AB  - RNAIII is the intracellular effector of the quorum-sensing system in
      Staphylococcus aureus. It is one of the largest regulatory RNAs (514 nucleotides
      long) that are known to control the expression of a large number of virulence
      genes. Here, we show that the 3' domain of RNAIII coordinately represses at the
      post-transcriptional level, the expression of mRNAs that encode a class of
      virulence factors that act early in the infection process. We demonstrate that
      the 3' domain acts primarily as an antisense RNA and rapidly anneals to these
      mRNAs, forming long RNA duplexes. The interaction between RNAIII and the mRNAs
      results in repression of translation initiation and triggers endoribonuclease III
      hydrolysis. These processes are followed by rapid depletion of the mRNA pool. In
      addition, we show that RNAIII and its 3' domain mediate translational repression
      of rot mRNA through a limited number of base pairings involving two loop-loop
      interactions. Since Rot is a transcriptional regulatory protein, we proposed that
      RNAIII indirectly acts on many downstream genes, resulting in the activation of
      the synthesis of several exoproteins. These data emphasize the multitude of
      regulatory steps affected by RNAIII and its 3' domain in establishing a network
      of S. aureus virulence factors.

PMID- 17545469
TI  - The RNA polymerase II CTD kinase Ctk1 functions in translation elongation.
AB  - Translation is a highly complex process that is regulated by a multitude of
      factors. Here, we show that the conserved kinase Ctk1 functions in translation by
      enhancing decoding fidelity. Ctk1 associates with translating ribosomes in vivo
      and is needed for efficient translation. Ctk1 phosphorylates Rps2, a protein of
      the small ribosomal subunit, on Ser 238. Importantly, Ctk1-depleted as well as
      rps2-S238A mutant cells show a defect in translation elongation through an
      increase in the frequency of miscoding. The role of Ctk1 in translation may be
      conserved as the mammalian homolog of Ctk1, CDK9, also associates with polysomes.
      Since Ctk1 interacts with the TREX (transcription and mRNA export) complex, which
      couples transcription to mRNA export, Ctk1/CDK9 might bind to correctly processed
      mRNPs during transcription and accompany the mRNP to the ribosomes in the
      cytoplasm, where Ctk1 enhances efficient and accurate translation of the mRNA.

PMID- 17545470
TI  - Infrequently transcribed long genes depend on the Set2/Rpd3S pathway for accurate
      transcription.
AB  - The presence of Set2-mediated methylation of H3K36 (K36me) correlates with
      transcription frequency throughout the yeast genome. K36me targets the Rpd3S
      complex to deacetylate transcribed regions and suppress cryptic transcription
      initiation at certain genes. Here, using a genome-wide approach, we report that
      the Set2-Rpd3S pathway is generally required for controlling acetylation at
      coding regions. When using acetylation as a functional readout for this pathway,
      we discovered that longer genes and, surprisingly, genes transcribed at lower
      frequency exhibit a stronger dependency. Moreover, a systematic screen using high
      resolution tiling microarrays allowed us to identify a group of genes that rely
      on Set2-Rpd3S to suppress spurious transcripts. Interestingly, most of these
      genes are within the group that depend on the same pathway to maintain a
      hypoacetylated state at coding regions. These data highlight the importance of
      using the functional readout of histone codes to define the roles of specific
      pathways.

PMID- 17545471
TI  - Endothelial nitric oxide synthase is dynamically expressed during bone marrow
      stem cell differentiation into endothelial cells.
AB  - This study was designed to investigate the developmental expression of
      endothelial nitric oxide synthase (eNOS) during stem cell differentiation into
      endothelial cells and to examine the functional status of the newly
      differentiated endothelial cells. Mouse adult multipotent progenitor cells
      (MAPCs) were used as the source of stem cells and were induced to differentiate
      into endothelial cells with vascular endothelial growth factor (VEGF) in serum
      free medium. Expression of eNOS in the cells during differentiation was evaluated
      with real-time PCR, nitric oxide synthase (NOS) activity, and Western blot
      analysis. It was found that eNOS, but no other NOS, was present in
      undifferentiated MAPCs. eNOS expression disappeared in the cells immediately
      after induction of differentiation. However, eNOS expression reoccurred at day 7
      during differentiation. Increasing eNOS mRNA, protein content, and activity were
      observed in the cells at days 14 and 21 during differentiation. The
      differentiated endothelial cells formed dense capillary networks on growth factor
      reduced Matrigel. VEGF-stimulated phosphorylation of extracellular signal
      regulated kinase (ERK)-1 and ERK-2 occurred in these cells, which was inhibited
      by NOS inhibitor N(G)-nitro-L-arginine methyl ester. In conclusion, these data
      demonstrate that eNOS is present in MAPCs and is dynamically expressed during the
      differentiation of MAPCs into endothelial cells in vitro.

PMID- 17545472
TI  - Involvement of cell surface ATP synthase in flow-induced ATP release by vascular
      endothelial cells.
AB  - Endothelial cells (ECs) release ATP in response to shear stress, a mechanical
      force generated by blood flow, and the ATP released modulates EC functions
      through activation of purinoceptors. The molecular mechanism of the shear stress
      induced ATP release, however, has not been fully elucidated. In this study, we
      have demonstrated that cell surface ATP synthase is involved in shear stress
      induced ATP release. Immunofluorescence staining of human pulmonary arterial ECs
      (HPAECs) showed that cell surface ATP synthase is distributed in lipid rafts and
      co-localized with caveolin-1, a marker protein of caveolae. Immunoprecipitation
      indicated that cell surface ATP synthase and caveolin-1 are physically
      associated. Measurement of the extracellular metabolism of [(3)H]ADP confirmed
      that cell surface ATP synthase is active in ATP generation. When exposed to shear
      stress, HPAECs released ATP in a dose-dependent manner, and the ATP release was
      markedly suppressed by the membrane-impermeable ATP synthase inhibitors
      angiostatin and piceatannol and by an anti-ATP synthase antibody. Depletion of
      plasma membrane cholesterol with methyl-beta-cyclodextrin (MbetaCD) disrupted
      lipid rafts and abolished co-localization of ATP synthase with caveolin-1, which
      resulted in a marked reduction in shear stress-induced ATP release. Pretreatment
      of the cells with cholesterol prevented these effects of MbetaCD. Downregulation
      of caveolin-1 expression by transfection of caveolin-1 siRNA also markedly
      suppressed ATP-releasing responses to shear stress. Neither MbetaCD, MbetaCD plus
      cholesterol, nor caveolin-1 siRNA had any effect on the amount of cell surface
      ATP synthase. These results suggest that the localization and targeting of ATP
      synthase to caveolae/lipid rafts is critical for shear stress-induced ATP release
      by HPAECs.

PMID- 17545473
TI  - Heart failure progression is accelerated following myocardial infarction in type
      2 diabetic rats.
AB  - Clinical studies have shown a greater incidence of myocardial infarction in
      diabetic patients, and following an infarction, diabetes is associated with an
      increased risk for the development of left ventricular (LV) dysfunction and heart
      failure. The goal of this study was to determine if the progression of heart
      failure following myocardial infarction in type 2 diabetic (T2D) rats is
      accelerated compared with nondiabetic rats. Male nondiabetic Wistar-Kyoto (WKY)
      and T2D Goto-Kakizaki (GK) rats underwent coronary artery ligation or sham
      surgery to induce heart failure. Postligation (8 and 20 wk), two-dimensional
      echocardiography and LV pressure measurements were made. Heart failure
      progression, as assessed by enhanced LV remodeling and contractile dysfunction,
      was accelerated 8 wk postligation in the T2D animals. LV remodeling was evident
      from increased end-diastolic and end-systolic diameters and areas in the GK
      compared with the WKY infarcted group. Furthermore, enhanced LV contractile
      dysfunction was evident from a greater deterioration in fractional shortening and
      enhanced myocardial performance index (an index of global LV dysfunction) in the
      GK infarcted group. This accelerated progression was accompanied by greater
      increases in atrial natriuretic factor and skeletal alpha-actin (gene markers of
      heart failure and hypertrophy) mRNA levels in GK infarcted hearts. Despite
      similar decreases in metabolic gene expression (i.e., peroxisome proliferator
      activated receptor-alpha-regulated genes associated with fatty acid oxidation)
      between infarcted WKY and GK rat hearts, myocardial triglyceride levels were
      elevated in the GK hearts only. These results, demonstrating enhanced remodeling
      and LV dysfunction 8 wk postligation provide evidence of an accelerated
      progression of heart failure in T2D rats.

PMID- 17545474
TI  - Dynamic changes in nitric oxide and mitochondrial oxidative stress with site
      dependent differential tissue response during anoxic preconditioning in rat
      heart.
AB  - In this study, dynamic changes in nitric oxide (NO) and mitochondrial superoxide
      (O(2)(*-)) were examined during anoxic preconditioning (AP) in rat heart model.
      AP and anoxia-reoxygenation (A/R) were performed on isolated hearts and single
      cardiomyocytes. The cellular insult in the form of infarct size and DNA damage
      were localized and correlated with NO synthases (endothelial and inducible)
      expression levels. The results showed that endocardium was the most affected
      region in AP groups, whereas the larger area of infarct was confined to mid- and
      epicardium in the A/R group. Interestingly, a high-level expression of
      immunofluorescent NO synthases was restricted to viable areas in the AP. In
      contrast to the gradual increase in O(2)(*-) level that occurred in the AP group,
      a sudden massive increase in its level was demonstrated at the onset of
      reoxygenation in the A/R group. The observed increase in NO production during
      reoxygenation in the AP group was attenuated by inducible NO synthase inhibitor.
      The study revealed, on a real-time basis, the role played by preconditioning for
      modulating NO and O(2)(*-) levels on behalf of cell survival. The results afford
      a better understanding of cardiac-adapting mechanism during AP and the role of
      inducible NO synthase in this important phenomenon.

PMID- 17545475
TI  - Influence of channel subunit composition on L-type Ca2+ current kinetics and
      cardiac wave stability.
AB  - Previous studies have demonstrated that the slope of the function relating the
      action potential duration (APD) and the diastolic interval, known as the APD
      restitution curve, plays an important role in the initiation and maintenance of
      ventricular fibrillation. Since the APD restitution slope critically depends on
      the kinetics of the L-type Ca(2+) current, we hypothesized that manipulation of
      the subunit composition of these channels may represent a powerful strategy to
      control cardiac arrhythmias. We studied the kinetic properties of the human L
      type Ca(2+) channel (Ca(v)1.2) coexpressed with the alpha(2)delta-subunit alone
      (alpha(1C) + alpha(2)delta) or in combination with beta(2a), beta(2b), or beta(3)
      subunits (alpha(1C) + alpha(2)delta + beta), using Ca(2+) as the charge carrier.
      We then incorporated the kinetic properties observed experimentally into the L
      type Ca(2+) current mathematical model of the cardiac action potential to
      demonstrate that the APD restitution slope can be selectively controlled by
      altering the subunit composition of the Ca(2+) channel. Assuming that beta(2b)
      most closely resembles the native cardiac L-type Ca(2+) current, the absence of
      beta, as well as the coexpression of beta(2a), was found to flatten restitution
      slope and stabilize spiral waves. These results imply that subunit modification
      of L-type Ca(2+) channels can potentially be used as an antifibrillatory
      strategy.

PMID- 17545476
TI  - Smooth muscle sparklet Ca(v) channels defined: 1.2 is the number.

PMID- 17545477
TI  - Factors released from embryonic stem cells inhibit apoptosis of H9c2 cells.
AB  - Our recent study (Singla DK, Hacker TA, Ma L, Douglas PS, Sullivan R, Lyons GE,
      Kamp TJ, J Mol Cell Cardiol 40: 195-200, 2006) suggests that transplanted
      embryonic stem (ES) cells subsequent to myocardial infarction differentiate into
      the major cell types in the heart and improve cardiac function. However, the
      extent of regeneration is relatively meager compared with the observed functional
      improvement. The mechanisms underlying their improved function are completely
      unknown. In this report, we provide evidence using a cell culture model system
      for novel mechanisms that involve the release of cytoprotective, anti-apoptotic
      factor(s) from ES cells and inhibit H(2)O(2)-induced apoptosis in the rat
      cardiomyocyte-derived cell line H9c2. Conditioned medium (CM) from growing mouse
      ES cells treated with and without H(2)O(2) was generated. Apoptosis was induced
      after exposure to H(2)O(2) in H9c2 cells for 2 h followed by replacement with
      fresh cell culture or ES cell-CM. After 24 h, H9c2 cells treated with both ES
      cell-CMs demonstrated significantly decreased apoptosis, as determined by
      terminal deoxynucleotidyl transferase dUTP-mediated nick-end labeling staining,
      apoptotic ELISA, caspase-3 activity, and DNA ladder. Next, using Luminex
      technology, we examined the presence of antiapoptotic proteins cystatin c,
      osteopontin, and clusterin and anti-fibrotic, tissue inhibitor of
      metalloproteinase-1 (TIMP-1) in both ES cell-CMs. The levels of released factors
      were 2- to 170-fold higher than those in H9c2 cell-CM. Antiapoptotic effects of
      ES cell-CM were significantly inhibited with TIMP-1 antibody, suggesting that
      TIMP-1 is an important factor to inhibit apoptosis. Furthermore, we used CM from
      an TIMP-1-overexpressing cell line and demonstrated that H(2)O(2)-induced
      apoptosis in the H9c2 cells was significantly inhibited. These observations
      demonstrate that factors released from ES cells contain antiapoptotic factors and
      that the effects are mediated by TIMP-1. Moreover, these findings suggest that
      released factors might be useful for therapeutic applications in ischemic heart
      disease as well as for many other diseases.

PMID- 17545478
TI  - The delta-opioid receptor agonist DADLE at reperfusion protects the heart through
      activation of pro-survival kinases via EGF receptor transactivation.
AB  - The specific delta-opioid receptor agonist [D-Ala(2)-D-Leu(5)]enkephalin (DADLE)
      protects against infarction in the heart when given before ischemia. In rabbit,
      this protection leads to phosphorylation of the pro-survival kinases Akt and
      extracellular signal-regulated kinase (ERK) and is dependent on transactivation
      of the epidermal growth factor receptor (EGFR). DADLE reportedly protects rat
      hearts at reperfusion. We therefore tested whether DADLE at reperfusion could
      protect isolated rabbit hearts subjected to 30 min of regional ischemia and 120
      min of reperfusion and whether this protection is dependent on Akt, ERK, and
      EGFR. DADLE (40 nM) was infused for 1 h starting 5 min before reperfusion and
      reduced infarct size from 31.0 +/- 2.3% in the control group to 14.6 +/- 1.6% (P
      = 0.01). This protection was abolished by cotreatment of the metalloproteinase
      inhibitor (MPI) and the EGFR inhibitor AG1478. In contrast, 20 nM DADLE, although
      known to be protective before ischemia, failed to protect. Western blotting
      revealed that DADLE's protection was correlated to increase in phosphorylation of
      the kinases Akt and ERK1 and -2 in reperfused hearts (2.5 +/- 0.5, 1.6 +/- 0.2,
      and 2.3 +/- 0.7-fold of baseline levels, P < 0.05 vs. control). The DADLE
      dependent increases in Akt and ERK1/2 phosphorylation were abolished by either
      MPI or AG1478, confirming a signaling through the EGFR pathway. Additionally,
      DADLE treatment increased phosphorylation of EGFR (1.4 +/- 0.2-fold, P = 0.03 vs.
      control). Thus the delta-opioid agonist DADLE protects rabbit hearts at
      reperfusion through activation of the pro-survival kinases Akt and ERK and is
      dependent on the transactivation of the EGFR.

PMID- 17545479
TI  - Activation of hypoxia-inducible factor-1 via prolyl-4 hydoxylase-2 gene silencing
      attenuates acute inflammatory responses in postischemic myocardium.
AB  - Emerging research suggests that oxidant-driven transcription of key
      cytokine/chemokine networks within the myocardium plays a crucial role in
      producing ischemia-reperfusion (I/R) injury. We recently showed that activation
      of hypoxia-inducible factor-1 (HIF-1) attenuated cardiac I/R injury. Diminished
      injury in these prior studies was associated with significant reductions in
      circulating interleukin-8 levels, suggesting that HIF-1 may play an important
      role in modulating postischemic cardiac inflammation. In the current study, we
      examined the role of HIF-1 activation in modulating proinflammatory chemokine
      [macrophage inflammatory protein (MIP)-2, cytokine-induced neutrophil
      chemoattractant factor (KC), and lipopolysaccharide-induced CXC chemokine (LIX)]
      and adhesion molecule [intercellular adhesion molecule (ICAM)-1] expression in
      murine cardiomyocytes in vitro (HL-1 cell line) and in intact murine hearts
      following in vivo I/R injury. Our results show that HIF-1 activation induced both
      pharmacologically by the prolyl hydroxylase inhibitor dimethyloxallyl glycine and
      via small-interfering RNA (siRNA)-mediated prolyl-4 hydroxylase-2 (P4HA2) gene
      silencing significantly attenuated tumor necrosis factor-alpha-induced chemokine
      (KC and LIX) and ICAM-1 expression in cardiomyocytes. In vivo, postischemic
      hearts obtained from animals receiving the P4HA2 siRNA (HIF-1 activation)
      exhibited significantly reduced CXC chemokine (MIP-2, KC, and LIX), CC chemokine
      (monocyte chemoattractant protein-1), and ICAM-1 expression when compared with
      postischemic hearts from either saline I/R controls or postischemic hearts from
      animals receiving a nontargeting control siRNA (no HIF-1 activation). Diminished
      chemokine and adhesion molecule expression in HIF-1-activated postischemic hearts
      was associated with significantly reduced polymorphonuclear leukocyte
      infiltration and myocardial infarct size (>60% reduction P4HA2 siRNA I/R vs.
      saline I/R, P < 0.001, n = 6). In conclusion, these results demonstrate for the
      first time that HIF-1 activation following infusion of siRNA to P4HA2 plays a key
      role in modulating I/R-associated cardiac inflammatory responses.

PMID- 17545480
TI  - The ligament of Marshall as a parasympathetic conduit.
AB  - The objective of the study was to investigate the morphology, distribution, and
      electrophysiological profile of the autonomic fibers that innervate the ligament
      of Marshall (LOM). Gross anatomical dissections were performed in 10 dogs.
      Sections of the left vagus nerve, left stellate ganglion, and the LOM were
      immunostained to identify adrenergic and cholinergic nerves. Hearts were also
      stained for acetylcholinesterase to identify epicardial cholinergic nerves. In
      vivo electrophysiological studies were performed in another 10 dogs before and
      after LOM ablation. The anatomical examination revealed that the LOM is
      innervated by a branch of the left vagus. Immunohistochemistry confirmed that
      these nerve bundles are predominantly cholinergic (cholinergic-to-adrenergic
      ratio of 12.6 +/- 3.9:1). Cholinergic nerves originating in the LOM were found to
      innervate surrounding left atrial structures, including the pulmonary veins, left
      atrial appendage, coronary sinus, and posterior left atrial fat pad. Ablation of
      the LOM significantly attenuated effective refractory period shortening at
      distant sites, such as pulmonary veins and left atrial appendage, in response to
      vagal stimulation (vagal-induced ERP decrease in the left atrium: baseline vs.
      postablation = 17 vs. 4%; P = 0.0056). In conclusion, the LOM contains a
      predominance of cholinergic nerve fibers. Cholinergic fibers arising from the LOM
      innervate surrounding structures and contribute to the electrophysiological
      profile of the left atrium. These findings may provide a basis for the role of
      the LOM in the genesis and maintenance of atrial fibrillation.

PMID- 17545481
TI  - Cardiomyocyte apoptosis in autoimmune cardiomyopathy: mediated via endoplasmic
      reticulum stress and exaggerated by norepinephrine.
AB  - Evidence suggests that the autoimmune cardiomyopathy produced by a peptide
      corresponding to the sequence of the second extracellular loop of the beta(1)
      adrenergic receptor (beta(1)-EC(II)) is mediated via a biologically active anti
      beta(1)-EC(II) antibody, but the mechanism linking the antibody to myocyte
      apoptosis and cardiac dysfunction has not been well elucidated. Since the beta(1)
      EC(II) autoantibody is a partial beta(1)-agonist, we speculate that the
      cardiomyopathy is produced by the beta(1)-receptor-mediated stimulation of the
      CaMKII-p38 MAPK-ATF6 signaling pathway and endoplasmic reticulum (ER) stress, and
      that excess norepinephrine (NE) exaggerates the cardiomyopathy. Rabbits were
      randomized to receive beta(1)-EC(II) immunization, sham immunization, NE pellet,
      or beta(1)-EC(II) immunization plus NE pellet for 6 mo. Heart function was
      measured by echocardiography and catheterization. Myocyte apoptosis was
      determined by terminal deoxytransferase-mediated dUTP nick-end labeling and
      caspase-3 activity, whereas CaMKII, MAPK family (JNK, p38, ERK), and ER stress
      signals (ATF6, GRP78, CHOP, caspase-12) were measured by Western blot,
      immunohistochemistry, and kinase activity assay. beta(1)-EC(II) immunization
      produced progressive LV dilation, systolic dysfunction, and myocyte apoptosis.
      These changes were associated with activation of GRP78 and CHOP and increased
      cleavage of caspase-12, as well as increased CaMKII activity, increased
      phosphorylation of p38 MAPK, and nucleus translocation of cleaved ATF6. NE pellet
      produced additive effects. In addition, KN-93 and SB 203580 abolished the
      induction of ER stress and cell apoptosis produced by the beta(1)-EC(II) antibody
      in cultured neonatal cardiomyocytes. Thus ER stress occurs in autoimmune
      cardiomyopathy induced by beta(1)-EC(II) peptide, and this is enhanced by
      increased NE and caused by activation of the beta(1)-adrenergic receptor-coupled
      CaMKII, p38 MAPK, and ATF6 pathway.

PMID- 17545482
TI  - Parvalbumin isoforms differentially accelerate cardiac myocyte relaxation
      kinetics in an animal model of diastolic dysfunction.
AB  - The cytosolic Ca(2+)/Mg(2+)-binding protein alpha-parvalbumin (alpha-Parv) has
      been shown to accelerate cardiac relaxation; however, beyond an optimal
      concentration range, alpha-Parv can also diminish contractility. Mathematical
      modeling suggests that increasing Parv's Mg(2+) affinity may lower the effective
      concentration of Parv ([Parv]) to speed relaxation and, thus, limit Parv-mediated
      depressed contraction. Naturally occurring alpha/beta-Parv isoforms show
      divergence in amino acid primary structure (57% homology) and cation-binding
      affinities, with beta-Parv having an estimated 16% greater Mg(2+) affinity and
      approximately 200% greater Ca(2+) affinity than alpha-Parv. We tested the
      hypothesis that, at the same or lower estimated [Parv], mechanical relaxation
      rate would be more significantly accelerated by beta-Parv than by alpha-Parv.
      Dahl salt-sensitive (DS) rats were used as an experimental model of diastolic
      dysfunction. Relaxation properties were significantly slowed in adult cardiac
      myocytes isolated from DS rats compared with controls: time from peak contraction
      to 50% relaxation was 57 +/- 2 vs. 49 +/- 2 (SE) ms (P < 0.05), validating this
      model system. DS cardiac myocytes were subsequently transduced with alpha- or
      beta-Parv adenoviral vectors. Upon Parv gene transfer, beta-Parv caused
      significantly faster relaxation than alpha-Parv (P < 0.05), even though estimated
      [beta-Parv] was approximately 10% of [alpha-Parv]. This comparative analysis
      showing distinct functional outcomes raises the prospect of utilizing naturally
      occurring Parv variants to address disease-associated slowed cardiac relaxation.

PMID- 17545483
TI  - Three distinct phases of VF during global ischemia in the isolated blood-perfused
      pig heart.
AB  - Changes in ventricular fibrillation (VF) organization occurring after the onset
      of global ischemia are relevant to defibrillation and survival but remain poorly
      understood. We hypothesized that ischemia-specific dynamic instability of the
      action potential (AP) causes a loss of spatiotemporal periodicity of propagation
      and broadening of the electrocardiogram (ECG) frequency spectrum during VF in the
      ischemic myocardium. We recorded voltage-sensitive fluorescence of di-4-ANEPPS
      (anterior left ventricle, 35 x 35 mm, 64 x 64 pixels) and the volume-conducted
      ECG in six blood-perfused hearts during 10 min of VF and global ischemia. We used
      coefficient of variation (CV) to estimate variability of AP amplitude, AP
      duration, and diastolic interval (CV-APA, CV-APD, and CV-DI, respectively). We
      computed excitation median frequency (Median_F), spectral width of the AP and ECG
      (SpW-AP and SpW-ECG, respectively), wavebreak incidence (WBI), and recurrence of
      propagation direction (RPD). We found three distinct phases of local VF dynamics:
      "relatively periodic" (<or=1 min, high Median_F, moderate AP variability, high
      WBI, low RPD), "highly periodic" (1-2 min, reduced Median_F, low AP variability,
      low WBI, high RPD), and "aperiodic" (3-10 min, low Median_F, high AP variability,
      high WBI, low RPD). In one experiment, spontaneous conversion from the aperiodic
      to the highly periodic phase occurred after 5 min of ischemia. The SpW-ECG was
      correlated with SpW-AP, CV-APD, and CV-APA. We conclude that 1) at least three
      distinct phases of VF dynamics are present in our model, and 2) the newly
      described aperiodic phase is related to ischemia-specific dynamic instability of
      the AP shape, which underlies broadening of the ECG spectrum during VF evolution.

PMID- 17545484
TI  - Effect of chemical stabilizers of hypoxia-inducible factors on early lung
      development.
AB  - Low oxygen stimulates pulmonary vascular development and airway branching and
      involves hypoxia-inducible factor (HIF). HIF is stable and initiates expression
      of angiogenic factors under hypoxia, whereas normoxia triggers hydroxylation of
      the HIF-1alpha subunit by prolyl hydroxylases (PHDs) and subsequent degradation.
      Herein, we investigated whether chemical stabilization of HIF-1alpha under
      normoxic (20% O(2)) conditions would stimulate vascular growth and branching
      morphogenesis in early lung explants. Tie2-LacZ (endothelial LacZ marker) mice
      were used for visualization of the vasculature. Embryonic day 11.5 (E11.5) lung
      buds were dissected and cultured in 20% O(2) in the absence or presence of cobalt
      chloride (CoCl(2), a hypoxia mimetic), dimethyloxalylglycine (DMOG; a nonspecific
      inhibitor of PHDs), or desferrioxamine (DFO; an iron chelator). Vascularization
      was assessed by X-gal staining, and terminal buds were counted. The fine vascular
      network surrounding the developing lung buds seen in control explants disappeared
      in CoCl(2)- and DFO-treated explants. Also, epithelial branching was reduced in
      the explants treated with CoCl(2) and DFO. In contrast, DMOG inhibited branching
      but stimulated vascularization. Both DFO and DMOG increased nuclear HIF-1alpha
      protein levels, whereas CoCl(2) had no effect. Since HIF-1alpha induces VEGF
      expression, the effect of SU-5416, a potent VEGF receptor (VEGFR) blocker, on
      early lung development was also investigated. Inhibition of VEGFR2 signaling in
      explants maintained under hypoxic (2% O(2)) conditions completely abolished
      vascularization and slightly decreased epithelial branching. Taken together, the
      data suggest that DMOG stabilization of HIF-1alpha during early development leads
      to a hypervascular lung and that airway branching proceeds without the
      vasculature, albeit at a slower rate.

PMID- 17545485
TI  - ErbB4 regulates fetal surfactant phospholipid synthesis in primary fetal rat type
      II cells.
AB  - Insufficient fetal surfactant production leads to respiratory distress syndrome
      among preterm infants. Neuregulin signals the onset of fetal surfactant
      phospholipid synthesis through formation of erbB receptor dimers. We hypothesized
      that erbB4 downregulation in fetal type II epithelial cells will downregulate not
      only fetal surfactant phospholipid synthesis, but also affect proliferation and
      erbB receptor localization. We tested these hypotheses using small interfering
      RNA (siRNA) directed against the erbB4 gene to silence erbB4 receptor function in
      cultures of primary day 19 fetal rat lung type II cells. ErbB4 siRNA treatment
      inhibited erbB4 receptor protein expression, fibroblast-conditioned medium
      induced erbB4 phosphorylation, and fetal surfactant phospholipid synthesis. Cell
      proliferation, measured as thymidine incorporation, was also inhibited by erbB4
      siRNA treatment. Downregulation of erbB4 receptor protein changed erbB1
      localization at baseline and after stimulation, as determined by confocal
      microscopy and subcellular fractionation. We conclude that erbB4 is an important
      receptor in the control of fetal lung type II cell maturation.

PMID- 17545486
TI  - A new mechanism for respiratory syncytial virus-induced beta2-adrenergic receptor
      insensitivity.

PMID- 17545487
TI  - Endothelial and epithelial signaling in the lung.
AB  - In recent years, pulmonary research has focused increasingly on the understanding
      of proinflammatory endothelial and epithelial signaling pathways underlying lung
      injury that is well known to be associated with high morbidity and mortality.
      Although traditionally considered separately, current research shows considerable
      convergence in epithelial and endothelial signaling mechanisms. This was well
      emphasized in the featured topic session held during the Experimental Biology
      2007 Meeting in Washington, D.C., that addressed the complex interdependence
      between signaling pathways in the two cellular phenotypes. Several perspectives
      on endothelial and epithelial signaling, as well as their contributions to
      pulmonary inflammation and damage, as presented and discussed in the session are
      summarized here.

PMID- 17545488
TI  - Resistin-like molecule-beta is an allergen-induced cytokine with inflammatory and
      remodeling activity in the murine lung.
AB  - Resistin-like molecule (RELM)-beta is a cysteine-rich cytokine implicated in
      insulin resistance and asthmatic responses, but its function remains an enigma.
      We now report that RELM-beta has a role in promoting airway inflammation and lung
      remodeling in the mouse lung. RELM-beta is strongly induced by diverse allergens
      and T helper type 2 (Th2) cytokines by an IL-13- and STAT6-dependent mechanism.
      To understand the in vivo role of RELM-beta, we delivered recombinant murine RELM
      beta intratracheally to naive mice. RELM-beta induced dose-dependent leukocyte
      accumulation (most prominently involving macrophages) and goblet cell
      hyperplasia. The most prominent effect induced by RELM-beta was increased
      perivascular and peribronchial collagen deposition. Mice genetically deficient in
      RELM-beta had reduced accumulation of collagen and goblet cell hyperplasia in an
      experimental model of allergic airway inflammation. In vitro experiments
      demonstrated that RELM-beta had fibroblast motogenic activity. These results
      identify RELM-beta as a Th2-associated cytokine with potent inflammatory and
      remodeling activity.

PMID- 17545489
TI  - Inhibition of serotonin-induced mitogenesis, migration, and ERK MAPK nuclear
      translocation in vascular smooth muscle cells by atorvastatin.
AB  - The HMG-CoA reductase inhibitors, statins, have pleiotropic effects which may
      include interference with the isoprenylation of Ras and Rho small GTPases.
      Statins have beneficial effects in animal models of pulmonary hypertension,
      although their mechanisms of action remain to be determined. Serotonin [5
      hydroxytryptamine (5-HT)] is implicated in the process of pulmonary artery smooth
      muscle (PASM) remodeling as part of the pathophysiology of pulmonary
      hypertension. We examined the effect of atorvastatin on 5-HT-induced PASM cell
      responses. Atorvastatin dose dependently inhibits 5-HT-induced mitogenesis and
      migration of cultured bovine PASM cells. Inhibition by atorvastatin was reversed
      by mevalonate and geranylgeranylpyrophosphate (GGPP) supplement, suggesting that
      the statin targets a geranylgeranylated protein such as Rho. Concordantly,
      atorvastatin inhibits 5-HT-induced cellular RhoA activation, membrane
      localization, and Rho kinase-mediated phosphorylation of myosin phosphatase-1
      subunit. Atorvastatin reduced activated RhoA-induced serum response factor
      mediated reporter activity in HEK293 cells, indicating that atorvastatin inhibits
      Rho signaling, and this was reversed by GGPP. While 5-HT-induced ERK MAP and Akt
      kinase activation were unaffected by atorvastatin, 5-HT-induced ERK nuclear
      translocation was attenuated in a GGPP-dependent fashion. These studies suggest
      that atorvastatin inhibits 5-HT-induced PASM cell mitogenesis and migration
      through targeting isoprenylation which may, in part, attenuate the Rho pathway, a
      mechanism that may apply to statin effects on in vivo models of pulmonary
      hypertension.

PMID- 17545490
TI  - Interleukin-17A modulates human airway epithelial responses to human rhinovirus
      infection.
AB  - Human rhinovirus (HRV) infections are associated with exacerbations of asthma and
      chronic obstructive pulmonary disease that are characterized by a selective
      neutrophil infiltration. IL-17A, a cytokine derived primarily from activated T
      cells, has been linked to neutrophilic inflammation of the airways. We
      hypothesized that IL-17A alters the response of HRV-infected epithelial cells to
      modulate airway inflammatory cell populations. IL-17A synergistically enhanced
      HRV-16-induced epithelial production of the neutrophil chemoattractant, IL-8, as
      well as human beta-defensin-2 (HBD-2), a chemoattractant for immature dendritic
      cells and memory T cells, but suppressed viral production of the eosinophil
      chemoattractant, RANTES. These effects were not due to alterations of viral
      uptake or replication by IL-17A. The synergy between HRV-16 and IL-17A for IL-8
      protein production was both dose- and time-dependent. IL-8 induction by IL-17A or
      HRV-16, alone and in combination, was reduced by inhibitors of the p38 and p44/42
      MAPK pathways. By contrast, induction of HBD-2 depended on the activation of the
      p38 and JNK pathways. The ability of IL-17A to synergistically enhance HRV
      induced IL-8 is mediated posttranscriptionally, since IL-8 promoter activation by
      the combination of the two stimuli was merely additive, whereas the combination
      of IL-17A and HRV-16 led to stabilization of IL-8 mRNA. Similarly, stimulation of
      HBD-2 promoter constructs by the combination of IL-17A and HRV-16 was no more
      than the sum of the individual responses. Further studies are needed to examine
      HBD-2 mRNA stability. Taken together, these data represent the first
      demonstration that IL-17A can modify epithelial responses to HRV in a manner that
      would be expected to favor the recruitment of neutrophils, immature dendritic
      cells, and memory T cells to the airways.

PMID- 17545491
TI  - Nicotine alters lung branching morphogenesis through the alpha7 nicotinic
      acetylcholine receptor.
AB  - There is abundant epidemiological data linking prenatal environmental tobacco
      smoke with childhood asthma and wheezing, but the underlying molecular and
      physiological mechanisms that occur in utero to explain this link remain
      unelucidated. Several studies suggest that nicotine, which traverses the
      placenta, is a causative agent. Therefore, we studied the effects of nicotine on
      lung branching morphogenesis using embryonic murine lung explants. We found that
      the expression of alpha(7) nicotinic acetylcholine receptors, which mediate many
      of the biological effects of nicotine, is highest in pseudoglandular stage lungs
      compared with lungs at later stages. We then studied the effects of nicotine in
      the explant model and found that nicotine stimulated lung branching in a dose
      dependent fashion. alpha-Bungarotoxin, an antagonist of alpha(7) nicotinic
      acetylcholine receptors, blocked the stimulatory effect of nicotine, whereas GTS
      21, a specific agonist, stimulated branching, thereby mimicking the effects of
      nicotine. Explants deficient in alpha(7) nicotinic acetylcholine receptors did
      not respond to nicotine. Nicotine also stimulated the growth of the explant.
      Altogether, these studies suggest that nicotine stimulates lung branching
      morphogenesis through alpha(7) nicotinic acetylcholine receptors and may
      contribute to dysanaptic lung growth, which in turn may predispose the host to
      airway disease in the postnatal period.

PMID- 17545492
TI  - Interleukin-1beta is the primary initiator of pulmonary inflammation following
      liver injury in mice.
AB  - Hepatic injury can lead to systemic and pulmonary inflammation through activation
      of NF-kappaB-dependent pathways and production of various proinflammatory
      cytokines. The exact mechanism remains unknown, although prior research suggests
      interleukin-1beta (IL-1beta) plays an integral role. Cultured murine alveolar
      macrophages were used to identify an optimized IL-1beta-specific short
      interfering RNA (siRNA) sequence, which then was encapsulated in liposomes and
      administered intraperitoneally to transgenic HLL mice (5'-HIV-LTR-Luciferase). A
      35% hepatic mass cryoablation in HLL and IL-1 receptor 1 knockout mice (IL1R1KO)
      was performed as a model for liver-induced pulmonary inflammation. IL-1beta siRNA
      pretreatment effectively and significantly reduced circulating IL-1beta levels at
      4 h post-hepatic injury. IL-6 also was suppressed in mice with impaired IL-1
      signaling pathways. NF-kappaB activation in the noninjured liver of HLL reporter
      mice pretreated with IL-1beta siRNA was found to be reduced compared with
      controls. Pulmonary NF-kappaB activity in this group also was diminished relative
      to controls. C-X-C chemokine levels in the lung remained significantly lower in
      IL-1 pathway-deficient mice. Similarly, lung myeloperoxidase content was
      unchanged from baseline at 24 h post-liver injury in IL-1beta siRNA-treated
      animals, whereas all other control groups demonstrated marked pulmonary
      neutrophilic infiltration. In conclusion, liver injury-induced lung inflammation
      in this model is mediated predominantly by IL-1beta. Knockdown of IL-1beta
      expression before hepatic injury led to significant reductions in both cytokine
      production and NF-kappaB activation. This translated to reduced pulmonary
      neutrophil accumulation. Pretreatment with IL-1beta siRNA may represent a novel
      intervention for preventing liver-mediated pulmonary inflammation.

PMID- 17545493
TI  - The significance of using US-Valued EQ-5D health states for comparative
      effectiveness and cost-effectiveness studies in US populations.

PMID- 17545494
TI  - Is all cost-effectiveness analysis local?

PMID- 17545495
TI  - Should we promote organ donor registries when so few registrants will end up
      being donors?
AB  - BACKGROUND: A major obstacle facing efforts to register organ donors is that the
      likelihood that any given registrant will die in such a way as to render his or
      her organs suitable for donation is extremely low. Such policies make sense only
      if the resources used to sign up an additional donor are proportional to the
      expected benefits. METHODS: Using data on historical donation patterns, estimates
      of the potential donor supply, and an estimate of the monetary value of an organ
      donor, the authors calculate the average value to society of a registrant as a
      function of age at registration. RESULT: Under a "first-person consent" regime,
      the value of a registrant ages 18 to 34 years is $1900. The value of registering
      individuals who have not already registered is even higher because these persons
      are more likely to become donors. If donor families have the right of refusal,
      the value of a registrant is substantially less, around $840. CONCLUSION: Given
      that most donor registries are fairly limited operations, piggybacking on
      drivers' license registration and renewal administration, results suggest that
      registries are cost-effective. Of course, a complete analysis awaits concrete
      data on the costs of operating registries and attracting new registrants.

PMID- 17545496
TI  - A graphical decision-theoretic model for neonatal jaundice.
AB  - BACKGROUND: Neonatal jaundice is treated daily at all hospitals. However, the
      routine, urgency, and case load of most doctors stop them from carefully
      analyzing all the factors that they would like to (and should) take into account.
      This article develops a complex decision support system for neonatal jaundice
      management. METHODS: The problem is represented by means of an influence diagram,
      including admission and treatment decisions. The corresponding uncertainty model
      is built with the aid of both historical data and subjective judgments. Parents
      and doctors were interviewed to elicit a multiattribute utility function. The
      decision analysis cycle is completed with sensitivity analyses and explanations
      of the results. RESULTS: The construction and use of this decision support system
      for jaundice management have induced a profound change in daily medical practice,
      avoiding aggressive treatments-there have been no exchange transfusions in the
      past 3 years-and reducing the lengths of stay at the hospital. More information
      is now taken into account to decide on treatments. Interestingly, after embarking
      on this modeling effort, physicians came to view jaundice as a much more
      difficult problem than they had initially thought. Comparisons between real cases
      and system proposals revealed that treatments by nonexpert doctors tend to be
      longer than what expert doctors would administer. CONCLUSION: The system is
      especially designed to help neonatologists in situations in which their lack of
      experience may lead to unnecessary treatments. Different points of view from
      several expert doctors and, more interestingly, from parents are taken into
      account. This knowledge gives a broader picture of the medical problem-
      incorporating new action criteria, new agents to intervene, more uncertainty
      variables-to get an insight into the suitability of each therapeutic decision for
      each patient situation. The benefits gained and the usefulness perceived by
      neonatologists are worth the increased and time-consuming effort of developing
      this complex system. Although specially designed for a specific hospital and for
      neonatal jaundice management, it can be easily adapted to other hospitals and
      problems.

PMID- 17545497
TI  - Why people refuse to make tradeoffs in person tradeoff elicitations: a matter of
      perspective?
AB  - OBJECTIVE: Person tradeoff (PTO) elicitations assess people's values for health
      states by asking them to compare the value of treatment programs. For example,
      people might be asked how many patients need to be cured of health condition X to
      equal the benefit of curing 100 people of condition Y. However, when faced with
      PTO elicitations, people frequently refuse to make quantifiable tradeoffs,
      exhibiting 2 kinds of refusals: 1) They say that 2 treatment programs have equal
      value, that curing 100 of X is just as good as curing 100 of Y, even if X is a
      less serious condition than Y, or 2) they say that the 2 programs are
      incomparable, that millions of people need to be cured of X to be as good as
      curing 100 of Y. The authors explore whether people would be more willing to make
      tradeoffs if the focus was changed from trading off groups of patients to
      choosing the best decision or evaluating treatment benefits. DESIGN: . Two
      randomized trials used diverse samples (N=2400) via the Internet to test for the
      effect of perspective on refusal rates. The authors predicted that perspectives
      that removed people from decision-making roles would increase their willingness
      make tradeoffs. RESULTS: Contrary to expectations, refusal rates increased when
      people were removed from decision-making roles. In fact, the more pressure put on
      people to make a decision, the less likely they were to refuse to make tradeoffs.
      CONCLUSION: To reduce PTO refusals, it is best to adopt a decision-maker
      perspective.

PMID- 17545498
TI  - Do risk attitudes differ across domains and respondent types?
AB  - OBJECTIVE: To evaluate differences in risk attitude across the domains of health
      and money for 2 types of respondents, patients and community members. METHODS:
      Two groups of respondents, patients with multiple sclerosis (n = 56) and members
      of the general community (n = 57), completed a survey that collected information
      on risk attitudes and socioeconomic and clinical variables (e.g., disability
      level). Risk attitude was measured using 2 standard-gamble questions on money and
      1 standard-gamble question on health outcomes. Multivariate regression was used
      to evaluate the relationship between risk attitude and respondent type (patient
      v. community), adjusting for covariates that could affect risk attitude. RESULTS:
      The median certainty equivalents for money gambles were significantly different
      from and less than the expected value of the gamble for both types of
      respondents. Median certainty equivalents for the health gamble were not
      significantly different from the expected value for either group of respondents.
      For all 3 gambles, there was no difference in median certainty equivalents
      between the 2 types of respondents in both unadjusted and adjusted analyses.
      CONCLUSIONS: Risk attitude varied across domains but not by respondent type.
      Patients and community members were predominantly risk neutral with respect to
      health outcomes and risk averse with respect to money. Research on risk
      preferences on money outcomes may not be an appropriate proxy for risk
      preferences regarding health outcomes. Risk preferences may depend more on
      characteristics of the choice than on respondent type.

PMID- 17545499
TI  - The default effect in end-of-life medical treatment preferences.
AB  - BACKGROUND: Living wills are intended to preserve patient autonomy, but recent
      studies suggest that they do not always have their desired effect. One possible
      explanation is that living wills do not capture the authentic preferences of the
      patients who write them but instead reflect transient contextual effects on
      preferences. PURPOSE: Two experiments examined whether end-of-life treatment
      preferences expressed in a living will were influenced by the presence of default
      options. METHOD: College students participated in 2 Web-based questionnaire
      experiments (Ns = 182 and 51). Participants were randomly assigned to 1 of 2 or 3
      default conditions. RESULTS: In experiment 1, participants expressed
      significantly different treatment preferences in 3 normatively equivalent, check
      box-formatted living wills that were either positively worded ("indicate medical
      treatments you would want administered"), negatively worded ("indicate treatments
      you would want withheld"), or of forced-choice format (P = 0.01). Participants
      expressed a stronger preference to receive treatment in the negatively worded
      document than in the positively worded document as a consequence of preferring
      the default option in both cases. Participants in experiment 2 were also
      influenced by the presence of a default option, but this time, while writing
      narrative living wills after viewing 1 of 2 sample living wills. In this
      experiment, the sample living will represented the default preference. The
      participants' own living wills tended to express preferences similar to those in
      the sample (P = 0.0005). CONCLUSION: The default manipulations in both
      experiments had potent but transient effects and influenced what participants
      wrote in their living wills but not their responses to later medical scenarios.
      Expression of end-of-life treatment preferences appears to be temporarily
      constructed from the decision-making context. These results have implications for
      surrogate decision making and the use of the living will as a tool to preserve
      patient autonomy.

PMID- 17545500
TI  - Factors influencing surgeons' decisions in elective cosmetic surgery
      consultations.
AB  - BACKGROUND: Current guidelines for surgeons' decisions about whether to offer
      cosmetic surgery are ineffective. Therefore, surgeons have to make difficult
      decisions on a case-by-case basis. The authors sought to identify the patient
      variables that influence surgeons' decisions in practice. DESIGN: A qualitative
      study first delineated, from observation of consultations and interviews with
      surgeons and other staff, variables that might influence their decisions. Then,
      in a cross-sectional survey of patients seeking cosmetic surgery, the authors
      measured these variables and tested whether they predicted the surgeons'
      decisions to offer surgery. PARTICIPANTS: Participants were 6 consultant plastic
      surgeons who assess cosmetic surgery referrals and 276 new patients aged 16 years
      or older referred to these surgeons. RESULTS: The qualitative study suggested
      that, as well as clinical factors (the probability of a satisfactory surgical
      outcome and the risks v. benefits of surgery), surgery was more likely to be
      offered where it was of low cost (i.e., minor skin surgery), physical symptoms or
      dysfunction were present, and abnormality of appearance was extreme. The role of
      patients' quality of life was unclear. The quantitative study confirmed that the
      probability of surgery was increased where requests were for minor skin
      procedures and by abnormality of patients' appearance. In patients seeking major
      body procedures, surgery was less likely when patients reported poor quality of
      life. CONCLUSION: Surgeons' decisions about whether to offer elective cosmetic
      surgery follow systematic rules. By incorporating the factors that surgeons use
      in their decision making, more effective guidelines about elective cosmetic
      surgery provision than are presently available could be developed.

PMID- 17545501
TI  - A comparison of EQ-5D index scores derived from the US and UK population-based
      scoring functions.
AB  - The authors recently introduced a new preference-based scoring function for the
      EQ-5D (D1 model) based on time tradeoff valuations from the general adult US
      population: In this study, they compared the EQ-5D index scores derived from the
      US (D1) algorithm to the more familiar UK (N3) algorithm. They compared
      preference-based EQ-5D index scores for all possible EQ-5D health states and
      differences in EQ-5D index scores between pairs of EQ-5D health states predicted
      by the D1 and N3 models. The responsiveness of D1- and N3-predicted EQ-5D index
      scores was assessed using simulated transitions between EQ-5D health states. The
      mean (SD) EQ-5D index scores for all 243 health states predicted by the D1 and N3
      models were 0.37 (0.23) and 0.14 (0.31), respectively. The mean (SD) absolute
      difference in EQ-5D index scores for all 29,403 pairs of health states was 0.25
      (0.19) and 0.35 (0.27), according to the D1 and N3 models, respectively. The D1
      and N3 models were consistent in predicting gains/losses for 27,592 (94%)
      transitions between EQ-5D health state pairs; Cohen effect size, calculated using
      these 27,592 consistent transitions, was 1.58 and 1.59 for the D1 and N3 models,
      respectively. Based on these simulation results, it appears that the D1 model
      would lead to smaller gains in quality-adjusted life years than the N3 model;
      however, their responsiveness appears to be similar. Empirical studies are needed
      to examine whether these 2 EQ-5D scoring functions would lead to different
      conclusions in cost-utility analyses.

PMID- 17545502
TI  - BCL6 programs lymphoma cells for survival and differentiation through distinct
      biochemical mechanisms.
AB  - The BCL6 transcriptional repressor is the most commonly involved oncogene in
      diffuse large B-cell lymphomas (DLBCLs). Constitutive expression of BCL6 mediates
      lymphomagenesis through aberrant proliferation, survival, and differentiation
      blockade. Binding of BCL6 to the SMRT/N-CoR corepressors mediates the BCL6
      survival effect in DLBCL. Although the basis for differentiation blockade is
      unknown in DLBCL, recent data suggest that BCL6 binding to the MTA3 corepressor
      might be involved. We report that BCL6 and MTA3 are coexpressed in normal
      germinal center B cells and DLBCL. Depletion of MTA3 in DLBCL cells induced a
      differentiation-related BCL6 target gene (PRDM1), but not target genes involved
      in survival. Accordingly, MTA3 and PRDM1 expression are mutually exclusive in
      germinal center B cells. We performed chromatin immunoprecipitation (ChIP)-on
      chip mapping of the PRDM1 locus, identifying a novel BCL6 binding site on intron
      3 of the PRDM1 gene, and show that BCL6 recruits MTA3 to this site. In DLBCL
      cells, MTA3 depletion induced plasmacytic differentiation but did not decrease
      viability of DLBCL cells. However, MTA3 depletion synergized with a specific BCL6
      inhibitor that blocks SMRT/N-CoR binding to decrease DLBCL viability. Taken
      together, these results show that BCL6 regulates distinct transcriptional
      programs through the SMRT/N-CoR and MTA3 corepressors, respectively, and provides
      a basis for combinatorial therapeutic targeting of BCL6.

PMID- 17545503
TI  - The role of jak2a in zebrafish hematopoiesis.
AB  - Janus kinase 2 (Jak2) transduces signals from hematopoietic cytokines, and a gain
      of-function mutation (Jak2(617V>F)) is associated with myeloproliferative
      diseases, particularly polycythemia vera. In this study, we examined the role of
      jak2a in zebrafish embryos in knock-down and overexpression studies using
      morpholinos (MOs) targeting the 5' untranslated region (UTR) (jak2a(UTR)-MO) and
      splice-site junction (jak2a(SS)-MO) of jak2a, a Jak inhibitor AG490 and a
      constitutive-active form of jak2a (jak2a(ca)). At 18 and 24 hours after
      fertilization (hpf), jak2a is expressed predominantly in the intermediate cell
      mass (ICM; site of primitive hematopoiesis) of wild-type and chordin morphant
      embryos (characterized by expansion of ICM). Both jak2a MOs and AG490 reduced
      gata1(+) (erythroid) cells in Tg(gata1:GFP) embryos, signal transducer and
      activation of transcription 5 (stat5) phosphorylation, and gene expression
      associated with early progenitors (scl and lmo2) and erythroid (gata1, alphahe1
      and betahe1) and myeloid (spi1 [early] and mpo [late]) lineages. The chordin
      morphant is associated with increased stat5 phosphorylation, and both jak2a MOs
      and treatment with AG490 significantly ameliorated ICM expansion and
      hematopoietic gene up-regulation in these embryos. Injection of plasmid encoding
      jak2a(ca) significantly increased erythropoiesis and expression of gata1,
      alphahe1 and betahe1, spi1, mpo, and l-plastin. In conclusion, zebrafish jak2a is
      involved in primitive hematopoiesis under normal and deregulated conditions.

PMID- 17545504
TI  - Farnesyltransferase inhibitors inhibit T-cell cytokine production at the
      posttranscriptional level.
AB  - Several cytoplasmic proteins, such as GTPases of the Ras family, containing a C
      terminal CAAX motif are prenylated by farnesyltransferase to facilitate
      localization to cellular membranes where activation occurs. Farnesyltransferase
      inhibitors (FTIs) interfere with this farnesylation process, thereby preventing
      proper membrane localization and rendering the proteins unavailable for
      activation. Currently, FTIs are being explored as antineoplastic agents for the
      treatment of several malignancies. However, since farnesylated proteins like Ras
      are also involved in intracellular signaling in lymphocytes, FTIs might interfere
      with T-cell activation. Based on this hypothesis we examined the effect of
      several FTIs on cytokine production in response to anti-CD3 + anti-CD28
      monoclonal antibodies or PMA + ionomycin. Murine Th1 and Th2 clones, stimulated
      in the presence of FTIs, showed a dose-dependent reduction of lineage-specific
      cytokine secretion (IFN-gamma, IL-2, IL-4, IL-5). However, no inhibition of ERK
      or JNK MAP kinases was observed, nor was induction of cytokine mRNA affected.
      Rather, intracellular cytokine protein synthesis was blocked. Inhibition of human
      T-cell INF-gamma production also was observed, correlating with reduced
      phosphorylation of p70S6K. These results indicate that FTIs inhibit T-cell
      activation at the posttranscriptional level and also suggest that they may have
      potential as novel immunosuppressive agents.

PMID- 17545506
TI  - Platelet particle formation by anti GPIIIa49-66 Ab, Ca2+ ionophore A23187, and
      phorbol myristate acetate is induced by reactive oxygen species and inhibited by
      dexamethasone blockade of platelet phospholipase A2, 12-lipoxygenase, and NADPH
      oxidase.
AB  - An HIV antibody (Ab) against platelet integrin GPIIIa49-66 induces complement
      independent platelet particle formation by the elaboration of reactive oxygen
      species (ROS) downstream of the activation of the platelet NADPH oxidase by the
      12-lipoxygenase (12-LO) product 12(S)-HETE. To determine whether other inducers
      of platelet particle formation also function via the induction of ROS, we
      examined the effects of the Ca(2+) ionophore A23187 and phorbol myristate acetate
      (PMA). Both agents induced oxidative platelet particle formation in an identical
      fashion as Ab, requiring Ca(2+) flux and 12(S)-HETE production as well as intact
      NADPH oxidase and 12-LO pathways. Since HIV-ITP patients with this Ab correct
      their platelet counts with dexamethasone (Dex), we examined the role of this
      steroid in this unique autoimmune disorder. Dex at therapeutic concentrations
      inhibited Ab-, A23187-, or PMA-induced platelet particle formation by inhibiting
      platelet PLA(2), 12-LO, and NADPH oxidase. The operational requirement of
      translocation of PLA(2), 12-LO, and NADPH oxidase components (p67 phox) from
      cytosol to membrane for induction of ROS was both inhibited and partially
      reversed by Dex in platelets. We conclude that (1) platelet particle formation
      can be induced by the generation of ROS; and (2) platelet PLA(2), 12-LO, NADPH
      oxidase, and cytosol membrane translocation, requirements for ROS production, are
      inhibited by Dex.

PMID- 17545507
TI  - Medicago truncatula root nodule proteome analysis reveals differential plant and
      bacteroid responses to drought stress.
AB  - Drought is one of the environmental factors most affecting crop production. Under
      drought, symbiotic nitrogen fixation is one of the physiological processes to
      first show stress responses in nodulated legumes. This inhibition process
      involves a number of factors whose interactions are not yet understood. This work
      aims to further understand changes occurring in nodules under drought stress from
      a proteomic perspective. Drought was imposed on Medicago truncatula 'Jemalong
      A17' plants grown in symbiosis with Sinorhizobium meliloti strain 2011. Changes
      at the protein level were analyzed using a nongel approach based on liquid
      chromatography coupled to tandem mass spectrometry. Due to the complexity of
      nodule tissue, the separation of plant and bacteroid fractions in M. truncatula
      root nodules was first checked with the aim of minimizing cross contamination
      between the fractions. Second, the protein plant fraction of M. truncatula
      nodules was profiled, leading to the identification of 377 plant proteins, the
      largest description of the plant nodule proteome so far. Third, both symbiotic
      partners were independently analyzed for quantitative differences at the protein
      level during drought stress. Multivariate data mining allowed for the
      classification of proteins sets that were involved in drought stress responses.
      The isolation of the nodule plant and bacteroid protein fractions enabled the
      independent analysis of the response of both counterparts, gaining further
      understanding of how each symbiotic member is distinctly affected at the protein
      level under a water-deficit situation.

PMID- 17545508
TI  - Synergid cell death in Arabidopsis is triggered following direct interaction with
      the pollen tube.
AB  - During angiosperm reproduction, one of the two synergid cells within the female
      gametophyte undergoes cell death prior to fertilization. The pollen tube enters
      the female gametophyte by growing into the synergid cell that undergoes cell
      death and releases its two sperm cells within the degenerating synergid cytoplasm
      to effect double fertilization. In Arabidopsis (Arabidopsis thaliana) and many
      other species, synergid cell death is dependent upon pollination. However, the
      mechanism by which the pollen tube causes synergid cell death is not understood.
      As a first step toward understanding this mechanism, we defined the temporal
      relationship between pollen tube arrival at the female gametophyte and synergid
      cell death in Arabidopsis. Using confocal laser scanning microscopy, light
      microscopy, transmission electron microscopy, and real-time observation of these
      two events in vitro, we demonstrate that synergid cell death initiates after the
      pollen tube arrives at the female gametophyte but before pollen tube discharge.
      Our results support a model in which a signaling cascade triggered by pollen tube
      synergid cell contact induces synergid cell death in Arabidopsis.

PMID- 17545509
TI  - Localization of members of the gamma-glutamyl transpeptidase family identifies
      sites of glutathione and glutathione S-conjugate hydrolysis.
AB  - gamma-Glutamyl transpeptidases (GGTs) are essential for hydrolysis of the
      tripeptide glutathione (gamma-glutamate-cysteine-glycine) and glutathione S
      conjugates since they are the only enzymes known to cleave the amide bond linking
      the gamma-carboxylate of glutamate to cysteine. In Arabidopsis thaliana, four GGT
      genes have been identified based on homology with animal GGTs. They are
      designated GGT1 (At4g39640), GGT2 (At4g39650), GGT3 (At1g69820), and GGT4
      (At4g29210). By analyzing the expression of each GGT in plants containing
      GGT:beta-glucuronidase fusions, the temporal and spatial pattern of degradation
      of glutathione and its metabolites was established, revealing appreciable overlap
      among GGTs. GGT2 exhibited narrow temporal and spatial expression primarily in
      immature trichomes, developing seeds, and pollen. GGT1 and GGT3 were coexpressed
      in most organs/tissues. Their expression was highest at sites of rapid growth
      including the rosette apex, floral stem apex, and seeds and might pinpoint
      locations where glutathione is delivered to sink tissues to supplement high
      demand for cysteine. In mature tissues, they were expressed only in vascular
      tissue. Knockout mutants of GGT2 and GGT4 showed no phenotype. The rosettes of
      GGT1 knockouts showed premature senescence after flowering. Knockouts of GGT3
      showed reduced number of siliques and reduced seed yield. Knockouts were used to
      localize and assign catalytic activity to each GGT. In the standard GGT assay
      with gamma-glutamyl p-nitroanilide as substrate, GGT1 accounted for 80% to 99% of
      the activity in all tissues except seeds where GGT2 was 50% of the activity.
      Protoplasting experiments indicated that both GGT1 and GGT2 are localized
      extracellularly but have different physical or chemical associations.

PMID- 17545510
TI  - Prognostic significance of fluorodeoxyglucose uptake in non-small cell lung
      cancer. A blurry picture?

PMID- 17545511
TI  - Multiple cytokine and growth factor serum biomarkers predict therapeutic response
      and survival in advanced-stage head and neck cancer patients.

PMID- 17545512
TI  - The mammalian target of rapamycin signaling pathway: twists and turns in the road
      to cancer therapy.
AB  - The immunosuppressive drug rapamycin played a key role in the functional
      characterization of mammalian target of rapamycin (mTOR), an unusual protein
      kinase that coordinates growth factor and nutrient availability with cell growth
      and proliferation. Several rapamycin-related compounds are now in various stages
      of clinical development as anticancer agents. This article highlights recent
      advances in our understanding of the mTOR signaling pathway and the implications
      of these findings for the clinical application of mTOR inhibitors in cancer
      patients.

PMID- 17545513
TI  - Interaction between cancer cells and stromal fibroblasts is required for
      activation of the uPAR-uPA-MMP-2 cascade in pancreatic cancer metastasis.
AB  - PURPOSE: Interaction between tumor cells and surrounding stromal fibroblast (SF)
      plays a critical role in tumor growth and invasion. The aim of the study is to
      determine the role of SF in regulating the invasive behaviors of pancreatic
      cancer by evaluating the mode of SF activating the urokinase plasminogen
      activator (uPA)-plasmin-matrix metalloproteinase (MMP)-2 cascade. EXPERIMENTAL
      DESIGN: The expression patterns of uPA, MMP-2, and uPA receptor (uPAR) in human
      metastatic pancreatic cancer were analyzed by immunohistochemistry and the roles
      of SF in activation of the uPA-plasmin-MMP-2 cascade were evaluated by
      coculturing pancreatic cancer cell lines with SF. RESULTS: uPA expression and
      fibroblastic uPAR expression were correlated with liver metastasis of human
      pancreatic cancer. MMP-2 rather than MMP-9 was activated in the metastatic
      pancreatic cancer. In the in vitro culture system, the coculture of peritumor
      fibroblasts with metastatic pancreatic cancer BxPc3 cells resulted in activation
      of MMP-2 and up-regulation of uPAR expression. In this coculture system, the uPA
      plasminogen cascade was involved in MMP-2 activation. This activation required a
      direct interaction between SF and cancer cells. In the coculture system,
      intergrin alpha(6)beta(1) expression was increased in BxPc3 cells, and blocking
      the function of integrin alpha(6)beta(1) decreased the activation of uPA and MMP
      2. This suggests that interaction between integrins of cancer cells and the uPARs
      of the SF might be involved in the activation of the uPAR-uPA-MMP-2 cascade.
      CONCLUSION: Our results suggest that SF plays a role in promoting pancreatic
      cancer metastasis via activation of the uPA-plasminogen-MMP-2 cascade.

PMID- 17545514
TI  - Molecular characterization of inflammatory genes in sentinel and nonsentinel
      nodes in melanoma.
AB  - PURPOSE: Identification of regional node metastasis is important for accurate
      staging and optimal treatment of early melanoma. We hypothesize that the nodal
      profile of immunoregulatory cytokines can confirm the identity of the first tumor
      draining regional node, i.e., the sentinel node (SN) and indicate its tumor
      status. EXPERIMENTAL DESIGN: RNA was extracted from freshly dissected and
      preserved nodal tissue of 13 tumor-negative SNs, 10 tumor-positive SNs
      (micrometastases <2 mm), and 11 tumor-negative non-SNs (NSN). RNA was converted
      into cDNA and then amplified by PCR. Expression of 96 cytokines and chemokines
      was assessed using cDNA microarray and compared by using hierarchical clustering.
      RESULTS: Fifty-seven genes were expressed at significantly (P < 0.05) different
      levels in SNs and NSNs (4 genes had higher expression, and 53 genes had lower
      expression in SNs). Expression levels of interleukin-13 (IL-13), leptin,
      lymphotoxin beta receptor (LTbR), and macrophage inflammatory protein 1b (MIP1b)
      were significantly higher (P < 0.04, P < 0.01, P < 0.05, and P < 0.01,
      respectively), and expression level of IL-11Ra was lower (P < 0.03) for tumor
      positive as compared with tumor-negative SN. Receiver-operator characteristics
      curve analyses showed that the area under the curve (AUC) for IL-13, leptin,
      LTbR, MIP1b, and IL-11Ra was 0.79, 0.83, 0.75, 0.81, and 0.77, respectively. The
      AUC for the five genes in combination was 0.973, suggesting high concordance of
      gene-expression profiles with SN staging. CONCLUSIONS: SNs have a different
      immunoregulatory cytokine profile than NSNs. The cytokine profile of tumor
      positive SNs; increased expression of IL-13, leptin, LTbR, and MIP1b and
      decreased expression of IL-11Ra, may provide clues to the local tumor lymph node
      interaction seen in the earliest steps of melanoma metastasis.

PMID- 17545515
TI  - DNA copy number gains at loci of growth factors and their receptors in salivary
      gland adenoid cystic carcinoma.
AB  - PURPOSE: Adenoid cystic carcinoma (ACC) is a malignant salivary gland tumor with
      a high mortality rate due to late, distant metastases. This study aimed at
      unraveling common genetic abnormalities associated with ACC. Additionally,
      chromosomal changes were correlated with patient characteristics and survival.
      EXPERIMENTAL DESIGN: Microarray-based comparative genomic hybridization was done
      to a series of 18 paraffin-embedded primary ACCs using a genome-wide scanning BAC
      array. RESULTS: A total of 238 aberrations were detected, representing more gains
      than losses (205 versus 33, respectively). Most frequent gains (>60%) were
      observed at 9q33.3-q34.3, 11q13.3, 11q23.3, 19p13.3-p13.11, 19q12-q13.43,
      21q22.3, and 22q13.33. These loci harbor numerous growth factor [fibroblast
      growth factor (FGF) and platelet-derived growth factor (PDGF)] and growth factors
      receptor (FGFR3 and PDGFRbeta) genes. Gains at the FGF(R) regions occurred
      significantly more frequently in the recurred/metastasized ACCs compared with
      indolent ACCs. Furthermore, patients with 17 or more chromosomal aberrations had
      a significantly less favorable outcome than patients with fewer chromosomal
      aberrations (log-rank = 5.2; P = 0.02). CONCLUSIONS: Frequent DNA copy number
      gains at loci of growth factors and their receptors suggest their involvement in
      ACC initiation and progression. Additionally, the presence of FGFR3 and PDGFRbeta
      in increased chromosomal regions suggests a possible role for autocrine
      stimulation in ACC tumorigenesis.

PMID- 17545516
TI  - Insulin-like growth factor-I produced by seminal vesicles: relationship to
      intraepithelial basal cell hyperplasia in the prostate.
AB  - PURPOSE: This study examined the seminal vesicle fluid (SVF) as a potential local
      source of insulin-like growth factor-I (IGF-I) in the peripheral zone of the
      prostate. EXPERIMENTAL DESIGN: IGF-I levels in seminal fluid were measured. The
      levels of the IGF-I receptor (IGF-IR) in its active, phosphorylated form as well
      as direct downstream targets were examined in the peripheral zone of the
      prostate. RESULTS: In situ, we find that the IGF-IR is activated in the
      peripheral zone in areas of atrophy, prostatic intraepithelial hyperplasia, and
      cancer. In addition, immunostaining reveals preferential activation of the IGF-IR
      in p63-positive cells in areas of intermediate basal cell hyperplasia in the
      peripheral zone, indicating that prostate progenitor cells are highly sensitive
      to increases in local IGF-I levels. These areas of basal cell hyperplasia occur
      at high incidence in the peripheral zone of the prostate. Relatively high levels
      of IGF-I were identified in SVF. In addition, we find that SVF can stimulate the
      proliferation of both normal and cancer-derived prostate cells. CONCLUSIONS:
      These results suggest that SVF is a local source of IGF-I that provides chronic
      stimulation of prostate cells. This chronic stimulation could contribute to the
      development of prostate cancer in older men.

PMID- 17545517
TI  - Identification and characterization of novel spliced variants of neuregulin 4 in
      prostate cancer.
AB  - PURPOSE: The neuregulin (NRG) 1, 2, and 3 genes undergo extensive alternative
      mRNA splicing, which results in variants that show structural and functional
      diversity. The aims of this study were to establish whether the fourth member of
      this family, NRG4, is expressed in prostate cancer, if it is alternatively
      spliced and whether any functional differences between the variants could be
      observed. EXPERIMENTAL DESIGN: The expression of NRG4 was determined using
      immunohistochemical staining of 40 cases of primary prostate cancer.
      Bioinformatic analysis and reverse transcription-PCR (RT-PCR) using NRG4 isotype
      specific primers on a panel of normal and prostate cancer cell lines were used to
      identify alternatively spliced NRG4 variants. Expression of these variants was
      determined using isotype-specific antibodies. Transfection into Cos-7 cells of
      two of these green fluorescent protein-tagged variants allowed analysis of their
      subcellular location. Four of the variants were chemically synthesized and tested
      for their ability to activate the ErbB4 receptor. RESULTS: NRG4 was variably
      expressed in the cytoplasm in the majority of prostate cancer cases, and in a
      subset of cases in the membrane, high levels were associated with advanced
      disease stage. Four novel NRG4 splice variants (NRGA2, NRG4 B1-3) were
      characterized, where each seemed to have a different subcellular location and
      were also expressed in the cytoplasm of the prostate tumors. NRG4 B3 was also
      present in endothelial cells. In transfected cells, the A type variant (NRG4 A1)
      was localized to the membrane, whereas the B type variant (NRG4 B1), which lacks
      the predicted transmembrane region, had an intracellular localization. Only the
      variants with an intact epidermal growth factor-like domain activated ErbB4
      signaling. CONCLUSION: NRG4 overexpression is associated with advanced-stage
      prostate cancer. The alternative splice variants may have different roles in cell
      signaling, some acting as classic receptor ligands and some with as-yet unknown
      functions.

PMID- 17545518
TI  - Cross-linking of signal transducer and activator of transcription 3--a molecular
      marker for the photodynamic reaction in cells and tumors.
AB  - PURPOSE: Photodynamic therapy (PDT) depends on the delivery of a photosensitizer
      to the target tissue that, under light exposure, produces singlet oxygen and
      other reactive oxygen species, which in turn cause the death of the treated cell.
      This study establishes a quantitative marker for the photoreaction that will
      predict the outcome of PDT. EXPERIMENTAL DESIGN: Cells in tissue culture, murine
      s.c. tumors, and endobronchial carcinomas in patients were treated with PDT, and
      the noncleavable cross-linking of the latent signal transducer and activator of
      transcription 3 (STAT3) was determined. RESULTS: Murine and human cancer cell
      lines reacted to PDT by an immediate covalent cross-linking of STAT3 to
      homodimeric and other complexes. The magnitude of this effect was strictly a
      function of the PDT reaction that is determined by the photosensitizer
      concentration and light dose. The cross-link reaction of STAT3 was proportional
      to the subsequent cytotoxic outcome of PDT. An equivalent photoreaction as
      detected in vitro occurred in tumors treated in situ with PDT. The light dose
      dependent STAT3 cross-linking indicated the relative effectiveness of PDT as a
      function of the distance of the tissue to the treating laser light source.
      Absence of cross-links correlated with treatment failure. CONCLUSIONS: The data
      suggest that the relative amount of cross-linked STAT3 predicts the probability
      for beneficial outcome, whereas absence of cross-links predicts treatment
      failure. Determination of STAT3 cross-links after PDT might be clinically useful
      for early assessment of PDT response.

PMID- 17545519
TI  - Identification of NTN4, TRA1, and STC2 as prognostic markers in breast cancer in
      a screen for signal sequence encoding proteins.
AB  - PURPOSE: In a previous screen using a signal-trap library, we identified a number
      of secreted proteins up-regulated in primary tumor cells isolated from invasive
      breast cancers. The purpose of this study was to assess the expression of these
      genes in human invasive breast tumors and to determine the significance of their
      expression for prognosis in breast cancer. EXPERIMENTAL DESIGN: A tissue
      microarray containing 245 invasive breast tumors from women treated with curative
      surgery followed by anthracycline-based chemotherapy and hormone therapy for the
      estrogen receptor (ER)-positive tumors was screened by in situ hybridization with
      probes against thrombospondin 3 (TSP3), insulin-like growth factor binding
      protein 7 (IGFBP7), tumor rejection antigen 1 (TRA1), stanniocalcin 2 (STC2), and
      netrin 4 (NTN4). Correlations between categorical variables were done using the
      chi(2) test and Fisher's exact test. Cumulative survival probabilities were
      calculated using the Kaplan-Meier method and multivariate survival analysis was
      done with Cox hazard model. A series of breast cancers were also stained with
      NTN4 antibodies. RESULTS: All five genes examined were expressed in invasive
      breast tumor cells. NTN4 protein expression was also confirmed by
      immunohistochemistry. Together, these data validate the design and screening of
      the signal-trap library. Univariate survival analysis revealed that expressions
      of TRA1, STC2, and NTN4 are correlated with longer disease-free survival and that
      TRA1 and NTN4 are associated with longer overall survival. Multivariate analysis
      showed that NTN4 is an independent prognostic factor of overall survival.
      CONCLUSIONS: This article describes the identification of three secreted
      proteins, NTN4, TRA1, and STC2, as potential novel prognostic markers in breast
      cancer.

PMID- 17545520
TI  - Methylation and silencing of protein tyrosine phosphatase receptor type O in
      chronic lymphocytic leukemia.
AB  - PURPOSE: Previous studies in our laboratory have shown the progressive
      methylation and suppression of the gene encoding protein tyrosine phosphatase,
      PTPRO, in the livers of rats fed a methyl-deficient diet that induces
      hepatocarcinogenesis. Subsequently, we observed the methylation of PTPRO in
      primary human lung tumors and also showed its potential tumor suppressor
      characteristics. The present study was undertaken to investigate whether the
      truncated form of PTPRO (PTPROt), specifically expressed in naive B lymphocytes,
      was also methylated and suppressed in chronic lymphocytic leukemia (CLL), a
      disease generally affecting B lymphocytes. EXPERIMENTAL DESIGN AND RESULTS:
      Initial screening showed that 60% of the 52 CLL samples analyzed using
      methylation-specific PCR assay were methylated compared with B lymphocytes from
      normal individuals, which were not methylated. The expression of PTPROt, as
      measured by semiquantitative reverse transcription-PCR, inversely correlated with
      methylation in the few samples tested. Analysis of additional samples (n = 50) by
      combined bisulfite restriction analysis showed that the PTPRO CpG island was
      methylated in 82% of patients with CLL compared with B lymphocytes from normal
      individuals. Furthermore, overall expression of PTPRO was reduced in CLL relative
      to normal lymphocytes. The PTPRO gene was also suppressed by methylation in the
      CLL cell line WaC3CD5, where it could be reactivated upon treatment with the DNA
      hypomethylating agent 5-AzaC. Ectopic expression of PTPROt in a nonexpressing
      cell line increased growth inhibition with fludarabine treatment, a therapy
      commonly used for CLL. CONCLUSION: This study reveals the potential role of PTPRO
      methylation and silencing in CLL tumorigenesis and also provides a novel
      molecular target in the epigenetic therapy.

PMID- 17545521
TI  - Nuclear factor-kappaB-related serum factors as longitudinal biomarkers of
      response and survival in advanced oropharyngeal carcinoma.
AB  - PURPOSE: Cytokines and growth factors modulated by transcription factor nuclear
      factor-kappaB and secreted by tumor and stromal cells are detectable in serum of
      patients with advanced cancers, including head and neck squamous cell carcinomas
      (SCC). Longitudinal changes in these serum factors could be early biomarkers of
      treatment response and survival. EXPERIMENTAL DESIGN: Interleukin (IL)-6, IL-8,
      growth-related oncogene-1 (GRO-1), vascular endothelial growth factor (VEGF), and
      hepatocyte growth factor (HGF) concentrations were determined by Luminex
      multiplex assay using serum obtained at baseline and every 3 months in a
      prospective study of 30 patients with locally advanced (stage III/IV)
      oropharyngeal SCC receiving chemoradiation therapy. The relationship between
      baseline and direction of change in individual and multiple cytokines with cause
      specific and disease-free survival was determined by Cox proportional hazards
      models and Kaplan-Meier survival analysis. Statistical analyses included
      adjustment for smoking status and response to chemoradiation. RESULTS: Three-year
      cause-specific and disease-free survival was 74.4% and 68.9%. Nonsmoking history
      (P = 0.05) and higher baseline VEGF (P = 0.003) correlated with increased
      survival. Longitudinal increases in levels of individual factors predicted
      decreased cause-specific survival when adjusted for smoking history [IL-6:
      relative risk (RR), 3.8; 95% confidence interval (95% CI), 2.0-7.4; P = 0.004; IL
      8: RR, 1.6; 95% CI, 1.2-2.2; P = 0.05; VEGF: RR, 3.0; 95% CI, 1.6-5.6; P = 0.01;
      HGF: RR, 2.9; 95% CI, 1.9-4.4; P = 0.02; and GRO-1: RR, 1.2; 95% CI, 1.1-1.3; P =
      0.02]. For a given individual, large increases in the upper quartile for any
      three or more factors predicted poorer cause-specific survival compared with
      patients with two or fewer large increases in factor levels (P = 0.004).
      CONCLUSIONS: Pretreatment VEGF levels and longitudinal change in IL-6, IL-8,
      VEGF, HGF, and GRO-1 may be useful as biomarkers for response and survival in
      patients with locally advanced oropharyngeal and head and neck SCC treated with
      chemoradiation.

PMID- 17545522
TI  - Methylation of CASP8, DCR2, and HIN-1 in neuroblastoma is associated with poor
      outcome.
AB  - PURPOSE: Epigenetic aberrations have been shown to play an important role in the
      pathogenesis of most cancers. To investigate the clinical significance of
      epigenetic changes in neuroblastoma, we evaluated the relationship between
      clinicopathologic variables and the pattern of gene methylation in neuroblastoma
      cell lines and tumors. EXPERIMENTAL DESIGN: Methylation-specific PCR was used to
      evaluate the gene methylation status of 19 genes in 14 neuroblastoma cell lines
      and 8 genes in 70 primary neuroblastoma tumors. Associations between gene
      methylation, established prognostic factors, and outcome were evaluated. Log-rank
      tests were used to identify the number of methylated genes that was most
      predictive of overall survival. RESULTS: Epigenetic changes were detected in the
      neuroblastoma cell lines and primary tumors, although the pattern of methylation
      varied. Eight of the 19 genes analyzed were methylated in >70% of the cell lines.
      Epigenetic changes of four genes were detected in only small numbers of cell
      lines. None of the cell lines had methylation of the other seven genes analyzed.
      In primary neuroblastoma tumors, high-risk disease and poor outcome were
      associated with methylation of DCR2, CASP8, and HIN-1 individually. Although
      methylation of the other five individual genes was not predictive of poor
      outcome, a trend toward decreased survival was seen in patients with a
      methylation phenotype, defined as > or =4 methylated genes (P = 0.055).
      CONCLUSION: Our study indicates that clinically aggressive neuroblastoma tumors
      have aberrant methylation of multiple genes and provides a rationale for
      exploring treatment strategies that include demethylating agents.

PMID- 17545523
TI  - Cytokeratin-18 is a useful serum biomarker for early determination of response of
      breast carcinomas to chemotherapy.
AB  - PURPOSE: With a widening arsenal of cancer therapies available, it is important
      to develop therapy-specific predictive markers and methods to rapidly assess
      treatment efficacy. We here evaluated the use of cytokeratin-18 (CK18) as a serum
      biomarker for monitoring chemotherapy-induced cell death in breast cancer.
      EXPERIMENTAL DESIGN: Different molecular forms of CK18 (caspase cleaved and
      total) were assessed by specific ELISA assays. Drug-induced release of CK18 was
      examined from breast carcinoma cells and tissue. CK18 protein composition was
      examined in serum. CK18 levels were determined in serum from 61 breast cancer
      patients during docetaxel or cyclophosphamide/epirubicin/5-fluorouracil (CEF)
      therapy. RESULTS: Caspase-cleaved CK18 molecules were released from monolayer
      cultures and tumor organ cultures to the extracellular compartment. CK18 was
      present in complexes with other cytokeratins in serum. Such CK18 protein
      complexes are remarkably stable, leading to favorable performance of CK18
      biomarker assays for clinical investigations. Docetaxel induced increased levels
      of caspase-cleaved CK18 in serum from breast cancer patients, indicating
      apoptosis. CEF therapy led to increases predominantly in uncleaved CK18,
      indicating induction of necrotic cell death in many tumors. The increase in total
      CK18 at 24 h of the first treatment cycle correlated to the clinical response to
      CEF therapy (P < 0.0001). CONCLUSIONS: Induction of necrotic cell death may
      explain the clinical efficacy of anthracycline-based therapy for breast
      carcinomas with defective apoptosis pathways. We suggest that CK18 biomarkers are
      useful for early prediction of the response to CEF therapy in breast cancer and
      may be useful biomarkers for clinical trials.

PMID- 17545524
TI  - Strong time dependence of the 76-gene prognostic signature for node-negative
      breast cancer patients in the TRANSBIG multicenter independent validation series.
AB  - PURPOSE: Recently, a 76-gene prognostic signature able to predict distant
      metastases in lymph node-negative (N(-)) breast cancer patients was reported. The
      aims of this study conducted by TRANSBIG were to independently validate these
      results and to compare the outcome with clinical risk assessment. EXPERIMENTAL
      DESIGN: Gene expression profiling of frozen samples from 198 N(-) systemically
      untreated patients was done at the Bordet Institute, blinded to clinical data and
      independent of Veridex. Genomic risk was defined by Veridex, blinded to clinical
      data. Survival analyses, done by an independent statistician, were done with the
      genomic risk and adjusted for the clinical risk, defined by Adjuvant! Online.
      RESULTS: The actual 5- and 10-year time to distant metastasis were 98% (88-100%)
      and 94% (83-98%), respectively, for the good profile group and 76% (68-82%) and
      73% (65-79%), respectively, for the poor profile group. The actual 5- and 10-year
      overall survival were 98% (88-100%) and 87% (73-94%), respectively, for the good
      profile group and 84% (77-89%) and 72% (63-78%), respectively, for the poor
      profile group. We observed a strong time dependence of this signature, leading to
      an adjusted hazard ratio of 13.58 (1.85-99.63) and 8.20 (1.10-60.90) at 5 years
      and 5.11 (1.57-16.67) and 2.55 (1.07-6.10) at 10 years for time to distant
      metastasis and overall survival, respectively. CONCLUSION: This independent
      validation confirmed the performance of the 76-gene signature and adds to the
      growing evidence that gene expression signatures are of clinical relevance,
      especially for identifying patients at high risk of early distant metastases.

PMID- 17545525
TI  - A polymorphism in HDM2 (SNP309) associates with early onset in superficial
      tumors, TP53 mutations, and poor outcome in invasive bladder cancer.
AB  - PURPOSE: The HDM2 gene represents one of the central nodes in the p53 pathway. A
      recent study reported the association of a single nucleotide polymorphism
      (SNP309) in the HDM2 promoter region with accelerated tumor formation in both
      hereditary and sporadic cancers. In this study, we aim to evaluate the SNP309 in
      bladder cancer and to link it to TP53 status. EXPERIMENTAL DESIGN: SNP309
      genotyping and TP53 mutation status were done on 141 bladder tumors and 8 bladder
      cancer cell lines using a RFLP strategy and TP53 genotyping arrays, respectively.
      Transcript profiling of a subset of cases (n = 41) was done using oligonucleotide
      arrays to identify genes differentially expressed regarding their SNP309 status.
      RESULTS: Of 141 bladder tumors analyzed, 36.9% displayed the SNP309 wild-type
      (WT; T/T) genotype, whereas 11.3% were homozygous (G/G) and 51.8% were
      heterozygous (T/G) cases. Patients with superficial disease and the G/G genotype
      had an earlier age on onset than those with the T/G or T/T genotypes (P = 0.029).
      Tumors with SNP309 WT genotype significantly displayed TP53 mutations when
      compared with tumors harboring G/G or T/G genotypes (P < 0.05). SNP309 WT cases
      had a poorer overall survival than cases with G/G and T/G genotypes (P < 0.05).
      TP53 mutation status provided enhanced prognostic value (P < 0.001). Transcript
      profiling identified TP53 targets among those differentially expressed between
      tumors displaying G/G or T/G SNP309 versus WT cases. CONCLUSIONS: SNP309 is a
      frequent event in bladder cancer, related to earlier onset of superficial disease
      and TP53 mutation status. SNP309 genotypes were found to be associated with
      clinical outcome.

PMID- 17545526
TI  - Distinction of hereditary nonpolyposis colorectal cancer and sporadic
      microsatellite-unstable colorectal cancer through quantification of MLH1
      methylation by real-time PCR.
AB  - PURPOSE: Promoter hypermethylation occurs frequently in tumors and leads to
      silencing of tumor-relevant genes like tumor suppressor genes. In a subset of
      sporadic colorectal cancers (CRC), inactivation of the mismatch repair gene MLH1
      due to promoter methylation causes high level of microsatellite instability (MSI
      H). MSI-H is also a hallmark of hereditary nonpolyposis colorectal cancer (HNPCC)
      in which mismatch repair inactivation results from germ-line mutations. For
      differentiation of sporadic and hereditary MSI-H tumor patients, MLH1 promoter
      methylation analysis is a promising tool but is not yet used in daily diagnostics
      because only qualitative techniques without standardization are available. The
      aim of this study is to establish a reliable and quantitative MLH1 methylation
      analysis technique and to define valid MLH1 methylation cutoff values for HNPCC
      diagnostics. EXPERIMENTAL DESIGN: We developed a new real-time PCR-based
      technique to detect and quantify methylation of both proximal and distal hMLH1
      promoter regions. We established and validated this technique in a cohort of 108
      CRCs [94 MSI-H and 16 microsatellite stable (MSS) cases] comprising a reference
      (n = 58) and a tester tumor group (n = 50). RESULTS: The reference tumor group
      contained 28 HNPCC with proven germ-line mutations or positive Amsterdam I
      criteria (median age, 37 years) and loss of MLH1 expression, 14 sporadic MSI-H
      CRC tumors with loss of MLH1 expression and BRAF V600E mutation (median age, 80.5
      years), and 16 sporadic MSS CRC (median age, 76.5 years). No MLH1 promoter
      methylation could be found in any MSS tumors. HNPCC patients showed no or low
      level of MLH1 promoter methylation. A cutoff value of 18% methylation extent
      could be determined in this study to define MLH1 hypermethylation specific for
      sporadic MSI-H cases. Methylation could also be verified qualitatively by melting
      point analysis. BRAF V600E mutations were not detected in any HNPCC patients (n =
      22 informative cases). CONCLUSION: According to the present data, quantitative
      MLH1 methylation analysis in MSI-H CRC is a valuable molecular tool to
      distinguish between HNPCC and sporadic MSI-H CRC. The detection of a BRAF V600E
      mutation further supports the exclusion of HNPCC.

PMID- 17545527
TI  - KIF14 messenger RNA expression is independently prognostic for outcome in lung
      cancer.
AB  - PURPOSE: The mitotic kinesin KIF14 is overexpressed in multiple cancers including
      lung cancer. Therefore, we investigated KIF14 expression in association with
      clinical variables and the effect of KIF14 on in vitro colony formation in non
      small-cell lung carcinoma. EXPERIMENTAL DESIGN: RNA was extracted from 129
      untreated, resected tumors and KIF14 expression was quantified by real-time
      reverse transcription-PCR. Associations with clinical variables were determined
      by standard statistical methods. KIF14 expression was knocked down by small
      interfering RNA in H1299 and HeLa cells; proliferation and growth in soft agar
      were assayed. RESULTS: Squamous cell carcinoma had the highest KIF14 level,
      followed by large-cell undifferentiated carcinoma, then adenocarcinoma (P =
      0.002). KIF14 level decreased with differentiation (P = 0.01) but was not
      associated with pathologic stage, T or N stage, or sex. When dichotomized about
      the median, KIF14 overexpression significantly decreased disease-free survival
      (Kaplan-Meier log-rank, P = 0.01) and trended toward decreasing overall survival
      (P = 0.08). In a univariate Cox proportional hazard regression, increasing KIF14
      expression decreased disease-free survival [P = 0.01; hazard ratio, 1.44 (95%
      confidence interval, 1.09-1.91)]. In a multivariate Cox regression, including
      stage, differentiation, histology, and tumor purity as covariates, KIF14
      overexpression remained an independent prognostic factor for disease-free
      survival [P = 0.01; hazard ratio, 1.45 (95% confidence interval, 1.09-1.94)].
      Knockdown of KIF14 in non-small-cell lung carcinoma and cervical carcinoma cell
      lines decreased proliferation and colony formation in soft agar. CONCLUSIONS:
      KIF14 expression is independently prognostic for disease-free survival in lung
      cancer and knockdown decreases tumorigenicity in vitro, showing that it is a
      clinically relevant oncogene and an exciting therapeutic target for further
      study.

PMID- 17545528
TI  - Association between the estrogen receptor alpha A908G mutation and outcomes in
      invasive breast cancer.
AB  - PURPOSE: Estrogen receptor alpha (ERalpha) predicts the natural history of breast
      cancer without intervening therapy. Here, we have optimized the detection of a
      somatic mutation, an A908G transition of ERalpha, and examined its association
      with clinical and biological features of invasive breast cancer. EXPERIMENTAL
      DESIGN: We compared two methods of sequencing to detect the A908G ERalpha
      mutation. We then used primer extension sequencing with genomic DNA isolated from
      invasive breast tumors to determine whether the mutation was associated with
      clinical outcome in 267 axillary node-negative and axillary node-positive breast
      tumors. The presence of the mutation and clinical variables were analyzed for
      association with recurrence-free survival and overall survival by Cox
      proportional hazards regression models. RESULTS: We determined that dye-labeled
      terminator sequencing was not adequate for detection of the A908G ERalpha
      mutation. The mutation was detected at a high frequency (50%) in invasive breast
      tumors using primer extension sequencing, and was found to be associated with
      clinical measures of poor outcome, including larger tumor size and axillary lymph
      node positivity. Although the mutation was associated with recurrence-free
      survival in univariate analysis, it was not an independent predictor of outcomes
      in multivariate analysis. CONCLUSIONS: Consistent with our previous finding of
      this somatic ERalpha mutation in breast ductal hyperplasias, we now present
      evidence that the A908G mutation is present in invasive breast tumors using an
      optimized sequencing method. We find that the mutation is significantly
      associated with aggressive biological tumor features, and with an unfavorable
      prognosis, but was not an independent prognostic marker in untreated patients.

PMID- 17545529
TI  - Changes of biochemical markers of bone turnover and YKL-40 following hormonal
      treatment for metastatic prostate cancer are related to survival.
AB  - PURPOSE: Elevated serum levels of biochemical markers of bone turnover and YKL-40
      in patients with metastatic prostate cancer (PC) at the time of diagnosis are
      associated to poor prognosis. In this study, we evaluated the value of these
      biomarkers in monitoring the patients during hormonal treatment. EXPERIMENTAL
      DESIGN: Serum procollagen type I N-terminal propeptide (PINP), bone-specific
      alkaline phosphatase (BAP), CTX-I, and YKL-40 were determined by ELISA in a
      longitudinal study of 106 patients with metastatic PC during treatment with total
      androgen ablation or parenteral estrogen. Serum samples were collected with 3
      months interval. Median observation time was 4.9 years (range, 3.6-6.2). A total
      of 78 patients died (64 within 7 months following the last blood sampling).
      RESULTS: After 6 months treatment, serum PINP, BAP, and YKL-40 decreased (P <
      0.0001), but not serum CTX-I compared with baseline values. Univariate Cox
      analysis showed that serum PINP at 6 months [log transformed and treated as a
      continuous variable; hazard ratio (HR), 2.2; P < 0.0001], serum BAP (HR, 1.8; P <
      0.0001), and serum CTX-I (HR, 2.4; P < 0.0001), but not serum YKL-40 (HR, 1.4; P
      = 0.16) were associated with survival. Multivariate Cox analysis including the
      biomarkers 6 months after the start of treatment showed that Soloway score (HR,
      3.9; P = 0.013), WHO tumor grade (HR, 3.9; P = 0.004), and serum PINP (HR, 2.2; P
      < 0.0001) were independent prognostic variables of survival. Scoring the
      biomarkers during treatment as time-dependent covariates in univariate Cox
      regression analysis showed that increases in serum PINP (HR, 2.0; P < 0.0001),
      BAP (HR, 2.1; P < 0.0001), and YKL-40 (HR, 2.1; P < 0.0001) were predictors of
      early death. CONCLUSIONS: Serial monitoring of serum PINP, BAP, CTX-I, and YKL-40
      in metastatic PC patients during hormonal treatment provided information of
      prognosis.

PMID- 17545530
TI  - Effect of positive bone marrow EBV in situ hybridization in staging and survival
      of localized extranodal natural killer/T-cell lymphoma, nasal-type.
AB  - PURPOSE: The aim of the study was to determine the effect of EBV-encoded RNA-1 in
      situ hybridization (EBER-1 ISH) in bone marrow specimens on survival outcome in
      patients with clinical stage I/II natural killer/T-cell lymphoma. EXPERIMENTAL
      DESIGN: We systematically did EBER-1 ISH on 182 archival bone marrow tissues from
      91 patients who were diagnosed of stage I/II natural killer/T-cell lymphoma and
      analyzed the correlation between bone marrow EBER-1 ISH status and survival. We
      defined minimal bone marrow involvement and definite bone marrow involvement to
      distinguish the subgroups who revealed EBV-positive cells from normal marrow by
      EBER-1 ISH from those who showed typical neoplastic cells in bone marrow
      biopsies. RESULTS: In total, 17 of the 91 (18.7%) patients showed positivity for
      EBER-1 ISH at least in one of the bilateral bone marrow biopsies with 14 minimal
      bone marrow involvements and 3 definite bone marrow involvements. Patients with
      positive bone marrow EBER-1 ISH showed significantly poorer overall survival than
      those who were negative for bone marrow EBER-1 ISH (median survival, 16.1 months
      versus not reached; P = 0.045). CONCLUSION: Considering a high proportion of
      stage I/II patients (15.4%) with minimal in bone marrow specimens, bone marrow
      EBER-1 ISH should be routinely done in all patients with localized disease for
      more accurate staging.

PMID- 17545531
TI  - Fluorodeoxyglucose uptake of primary non-small cell lung cancer at positron
      emission tomography: new contrary data on prognostic role.
AB  - PURPOSE: This prospective study evaluated the prognostic significance of (18)F
      fluorodeoxyglucose ((18)F-FDG) uptake in primary non-small cell lung cancer
      (NSCLC) at positron emission tomography, in a carefully staged population, while
      correcting for partial volume effects. EXPERIMENTAL DESIGN: Two hundred eight
      potentially resectable NSCLC patients were referred for FDG positron emission
      tomography staging after thoracic computed tomography. Each tumor stage was
      confirmed surgically, or for some stage IV tumors by additional imaging. The
      tumor maximum pixel-standardized uptake value (maxSUV) and the maxSUV partial
      volume corrected for lesion size (PVCmaxSUV) were compared with overall survival
      and disease-free survival using Cox proportional hazards regression. RESULTS:
      Stage distribution: stage I, 36%; stage II, 15%; stage III, 30%; stage IV, 19%.
      Patients were followed for a median of 33.6 months, with 90 deaths from NSCLC
      (median survival for all stages, 43.3 months). With respect to overall survival,
      the most significant cutoff value for both maxSUV and PVCmaxSUV was 7. MaxSUV >
      or =7 was significantly associated with an increased risk of death from NSCLC in
      univariable analysis, whereas PVCmaxSUV > or =7 was only marginally associated.
      However, in multivariable analyses, neither maxSUV > or =7 nor PVCmaxSUV > or =7
      provided significant additional prognostic information over stage, tumor size,
      and age. In the 103 patients who underwent surgical resection only, surgical
      stage, but not maxSUV or PVCmaxSUV, was univariably associated with survival or
      recurrence. SUV definitions based on lean body mass, body surface area, and
      plasma glucose correction yielded identical results. CONCLUSIONS: As expected,
      tumor stage is prognostic in NSCLC. However, tumor FDG uptake does not provide
      additional prognostic information. This prospective study contradicts prior
      reports.

PMID- 17545532
TI  - Body composition as an independent determinant of 5-fluorouracil-based
      chemotherapy toxicity.
AB  - PURPOSE: Evidence suggests that lean body mass (LBM) may be useful to normalize
      doses of chemotherapy. Data from a prospective study were used to determine if
      the highest doses of 5-fluorouracil (5-FU) per kilogram LBM would be associated
      with dose-limiting toxicity in stage II/III colon cancer patients treated with 5
      FU and leucovorin. EXPERIMENTAL DESIGN: Toxicity after cycle 1 was graded
      according to National Cancer Institute Common Toxicity Criteria, version 2.0.
      Muscle tissue was measured by computerized tomography. An extrapolation to the
      LBM compartment of the whole body was employed. RESULTS: Mean values of 5-FU/LBM
      of the entire population were different in terms of presence or absence of
      toxicity (P = 0.036). A cut point of 20 mg 5-FU/kg LBM seemed to be a threshold
      for developing toxicity (P = 0.005). This observation was pertinent to women
      (odds ratio, 16.73; P = 0.021). Women in this study had a relatively low
      proportion of LBM relative to their body surface area. CONCLUSION: Our study
      shows that low LBM is a significant predictor of toxicity in female patients
      administered 5-FU using the convention of dosing per unit of body surface area.
      We conclude that variation in toxicity between females and males may be partially
      explained by this feature of body composition.

PMID- 17545533
TI  - A phase I, randomized, open-label, parallel-cohort, dose-finding study of
      elacridar (GF120918) and oral topotecan in cancer patients.
AB  - PURPOSE: Breast cancer resistance protein (ABCG2) substantially limits the oral
      bioavailability of topotecan. Coadministration with elacridar, an inhibitor of
      breast cancer resistance protein-mediated drug transport, increases the
      bioavailability of topotecan. The aim of this study was to establish the lowest
      effective dose of elacridar to obtain maximum oral bioavailability of topotecan
      and to determine the optimal schedule of coadministration of oral topotecan and
      elacridar. In the second part of this study, dose-limiting toxicities and maximum
      tolerated dose of oral topotecan coadministered with elacridar, at a daily times
      five regimen administered every 21 days, were established. EXPERIMENTAL DESIGN:
      In part I, 20 patients were randomized to receive 100, 300, 500, 700, or 1,000 mg
      of elacridar on days 1 and 8 1 h before or simultaneously with 2.0 mg oral
      topotecan, which was also randomized. On day 15, all patients were treated with
      1.5 mg/m(2) i.v. topotecan. In part II of the study, patients were treated daily
      with oral topotecan and with the lowest effective dose of elacridar following
      from part I. The maximum tolerated dose and dose-limiting toxicity were
      determined in cohorts of three patients. Blood samples were taken on days 1, 8,
      and 15 of part I and on day 1 of cycles 1 and 2 of part II. RESULTS: Complete
      apparent oral bioavailability of topotecan (102 +/- 7%) for all treatment arms
      with elacridar in both schedules was seen in part I. In the topotecan dose
      escalation part, two dose-limiting toxicities were seen at the 2.5 mg topotecan
      dose level. CONCLUSION: The recommended schedule is 2.0 mg oral topotecan plus
      100 mg elacridar administered concomitantly daily times five every 21 days.

PMID- 17545534
TI  - A phase I biodistribution and pharmacokinetic trial of humanized monoclonal
      antibody Hu3s193 in patients with advanced epithelial cancers that express the
      Lewis-Y antigen.
AB  - PURPOSE: We report a first-in-man trial of a humanized antibody (hu3S193) against
      the Le(y) antigen. EXPERIMENTAL DESIGN: Patients with advanced Le(y)-positive
      cancers received four infusions of hu3S193 at weekly intervals, with four dose
      levels (5, 10, 20, and 40 mg/m(2)). The first infusion of hu3S193 was trace
      labeled with Indium-111, and biodistribution, pharmacokinetics, tumor uptake, and
      immune response were evaluated in all patients. RESULTS: A total of 15 patients
      (7 male/8 female; age range, 42-76 years; 6 breast, 8 colorectal cancer, and 1
      non-small-cell lung cancer) were entered into the study. Transient grade 1 to 2
      nausea and vomiting was observed following infusion of hu3S193 at the 40 mg/m(2)
      dose level only. There was one episode of dose-limiting toxicity with self
      limiting Common Toxicity Criteria grade 3 elevated alkaline phosphatase observed
      in one patient with extensive liver metastases. The biodistribution of (111)In
      hu3S193 showed no evidence of any consistent normal tissue uptake, and (111)In
      hu3S193 uptake was observed in cutaneous, lymph node, and hepatic metastases.
      Hu3S193 displayed a long serum half-life (T(1/2)beta = 189.63 +/- 62.17 h).
      Clinical responses consisted of 4 patients with stable disease and 11 patients
      with progressive disease, although one patient experienced a 89% decrease in a
      lymph node mass, and one patient experienced inflammatory symptoms in cutaneous
      metastases, suggestive of a biological effect of hu3S193. No immune responses
      (human anti-human antibody) to hu3S193 were observed. CONCLUSION: Hu3S193 is well
      tolerated and selectively targets tumors, and the long half-life and biological
      function in vivo of this antibody makes it an attractive potential therapy for
      patients with Le(y)-expressing cancers.

PMID- 17545535
TI  - Phase I and pharmacokinetic study of AI-850, a novel microparticle hydrophobic
      drug delivery system for paclitaxel.
AB  - PURPOSE: AI-850, paclitaxel in a novel polyoxyethylated castor oil-free
      hydrophobic microparticle delivery system, is being developed based on its
      favorable preclinical safety and antitumor activity profiles. The objectives of
      the study were to assess the feasibility and safety of administering AI-850 as a
      <30-min i.v. infusion without premedication every 3 weeks, determine the maximum
      tolerated dose and the phase II recommended dose of AI-850, study the
      pharmacokinetics of paclitaxel in this new formulation, and seek evidence of
      anticancer activity. EXPERIMENTAL DESIGN: This was an open-label phase I dose
      escalation study of AI-850 in patients with advanced solid malignancies. AI-850
      doses were escalated according to a modified Fibonacci scheme. Clinical and
      laboratory toxicity was monitored, and paclitaxel plasma concentrations were
      measured by liquid chromatography-tandem mass spectrometry. RESULTS: Twenty-two
      patients received 56 courses of AI-850 at five dose cohorts ranging from 36 to
      250 mg/m(2). Grade 4 neutropenia, either exceeding 5 days or complicated by
      fever, was dose limiting in two of six patients at 250 mg/m(2) AI-850. Three
      patients experienced grade 2 to 4 infusion-related adverse reactions. Toxicities,
      including fatigue, alopecia, nausea and vomiting, neuropathy, anorexia, and
      myalgia, were mild to moderate, reversible, and not dose related.
      Pharmacokinetics of free and total paclitaxel showed biexponential plasma decay
      and dose proportionality for maximum plasma paclitaxel concentration and area
      under the concentration versus time curve. Antitumor activity was documented in
      two patients with endometrial and tongue carcinomas. CONCLUSIONS: The
      administration of AI-850 as a brief infusion once every 3 weeks was feasible at
      doses up to 205 mg/m(2). The potential of AI-850 as an alternative to other
      approved paclitaxel formulations requires further clinical evaluation.

PMID- 17545536
TI  - A comparison of the pharmacokinetics and pharmacodynamics of docetaxel between
      African-American and Caucasian cancer patients: CALGB 9871.
AB  - PURPOSE: Increased clearance of drugs, such as oral cyclosporine, that are CYP3A
      and/or ABCB1 (P-gp/MDR1) substrates was reported in African-American compared
      with Caucasian patients. We hypothesized that the pharmacokinetics and
      pharmacodynamics of docetaxel, an i.v. administered cytotoxic and substrate for
      CYP3A4, CYP3A5, and ABCB1, would differ between African-American and Caucasian
      patients. EXPERIMENTAL DESIGN: We investigated population pharmacokinetics and
      pharmacodynamics and the pharmacogenetics of CYP3A4, CYP3A5, and ABCB1 in African
      American and Caucasian cancer patients who received docetaxel 75 or 100 mg/m(2)
      as a 1-h i.v. infusion. Plasma docetaxel concentrations were measured by high
      performance liquid chromatography. Clinical toxicity and absolute neutrophil
      count (ANC) were monitored on days 8, 15, and 22 postadministration of docetaxel.
      Using a limited sampling strategy and nonlinear mixed-effects modeling, each
      patient's docetaxel clearance was estimated. Genotyping for known polymorphisms
      in CYP3A4, CYP3A5, and ABCB1 was done. RESULTS: We enrolled 109 patients: 40
      African-Americans (26 males; 14 females), with a median age of 61 years (range,
      29-73), and 69 Caucasians (43 males; 26 females), with a median age of 63 years
      (range, 38-81). There was no difference in the geometric mean docetaxel clearance
      between African-American patients [40.3 L/h; 95% confidence interval (95% CI),
      19.3-84.1] and Caucasian patients (41.8 L/h; 95% CI, 22.0-79.7; P = 0.6). We
      observed no difference between African-American and Caucasian patients in the
      percentage decrease in ANC nor were docetaxel pharmacokinetic parameters related
      to the genotypes studied. CONCLUSIONS: Docetaxel clearance and its associated
      myelosuppression were similar in African-American and Caucasian cancer patients.

PMID- 17545537
TI  - Phase I trial of BAY 50-4798, an interleukin-2-specific agonist in advanced
      melanoma and renal cancer.
AB  - PURPOSE: BAY 50-4798 is an analogue of interleukin-2 that selectively activates T
      cells over natural killer cells. This phase I study was designed to determine the
      maximum tolerated dose (MTD) and safety of BAY 50-4798, screen for tumor
      response, and assess pharmacokinetics. EXPERIMENTAL DESIGN: Forty-five patients
      with metastatic melanoma or renal cancer were enrolled, 31 on escalating doses to
      determine the MTD, with 20 renal cell carcinoma patients treated at MTD to detect
      antitumor activity. BAY 50-4798 was delivered i.v. every 8 h, days 1 to 5 and 15
      to 19, and could be repeated after 9 weeks if tumor was stable or responding.
      RESULTS: The MTD was defined by and reported in terms of doses received. The
      doses tested ranged from 1.3 to 26.1 microg/kg, and the MTD was defined as 10.4
      microg/kg based on toxicities similar to those of aldesleukin. Two patients
      achieved partial responses, one with melanoma and one with renal cell carcinoma.
      Among all 45 patients, 53% and 9% experienced a grade 3 and 4 toxicity,
      respectively. Among the patients treated at the MTD of 10.4 microg/kg, 71% and
      10% experienced a grade 3 and 4 toxicity, respectively. Pharmacokinetics showed
      dose-dependent peak concentrations (C(max)) and area under the curve with a half
      life of approximately 2 h and no evidence of accumulation. Lymphocyte subset
      analysis confirmed the preferential expansion of T-cell subsets over natural
      killer cells. CONCLUSIONS: The antitumor activity of BAY 50-4798 in malignancies
      that respond to high-dose interleukin-2 was low. BAY 50-4798 might provide
      advantages over aldesleukin in antigen-specific immunotherapies.

PMID- 17545538
TI  - Multicenter clinical trial of bortezomib in relapsed/refractory Waldenstrom's
      macroglobulinemia: results of WMCTG Trial 03-248.
AB  - PURPOSE: Waldenstrom's macroglobulinemia (WM) is a B-cell disorder. Despite
      advances in the therapy, WM remains incurable. As such, novel therapeutic agents
      are needed for the treatment of WM. EXPERIMENTAL DESIGN: In this multicenter
      study, 27 patients with WM received up to eight cycles of bortezomib at 1.3
      mg/m(2) on days 1, 4, 8, and 11. All but one patient had relapsed/or refractory
      disease. RESULTS: Following therapy, median serum IgM levels declined from 4,660
      to 2,092 mg/dL (P < 0.0001). The overall response rate was 85%, with 10 and 13
      patients achieving minor and major responses, respectively. Responses were prompt
      and occurred at median of 1.4 months. The median time to progression for all
      responding patients was 7.9 (range, 3-21.4+) months. The most common grade III/IV
      toxicities occurring in > or =5% of patients were sensory neuropathies (22.2%),
      leukopenia (18.5%), neutropenia (14.8%), dizziness (11.1%), and thrombocytopenia
      (7.4%). Sensory neuropathies resolved or improved in nearly all patients
      following cessation of therapy. CONCLUSIONS: The results of these studies show
      that bortezomib is an active agent in relapsed and refractory WM.

PMID- 17545539
TI  - A novel approach for treatment of unresectable pancreatic cancer: design of
      radioactive stents and trial studies on normal pigs.
AB  - PURPOSE: Patients diagnosed with pancreatic cancer typically have a poor
      prognosis. The aims of these studies were to design radioactive stents and to
      evaluate the feasibility and safety of the stents in animals. EXPERIMENTAL
      DESIGN: To combine the effects of stents and brachytherapy, plastic stents with
      inserted iodine-125 seeds were designed and tested in 18 normal pigs. The pigs
      were divided into five groups on the basis of radiation dose. The estimated
      radiation dose at a 5-mm radial distance from the axis of the seeds was 50 Gy in
      group A, 100 Gy in group B, 150 Gy in group C, and 200 Gy in group D, with four
      pigs in each group. In the control group (n = 2), the same plastic stents with
      non-radioactive seeds were implanted in the pancreatic duct. RESULTS: The
      procedures were successfully done on 14 of 18 (78%) pigs, whereas pancreatic duct
      perforation occurred in four pigs (22%). The thickened wall of the dilated
      pancreatic duct was clearly observed in the control group. However, the normal
      morphologic structure of the pancreatic duct wall disappeared in the experimental
      groups. Histopathologic examination revealed that the stents were surrounded with
      necrotic tissues and lateral fibrous tissues. During the follow-up period, the
      width of outside fibrous tissues gradually increased. CONCLUSIONS: These results
      indicate that the radioactive stents are safe in all dose groups, and it is
      feasible to design a special radioactive stent for each patient according to the
      size, shape, and position of the pancreatic tumor.

PMID- 17545540
TI  - Functional up-regulation of human leukocyte antigen class I antigens expression
      by 5-aza-2'-deoxycytidine in cutaneous melanoma: immunotherapeutic implications.
AB  - PURPOSE: To investigate the potential of the DNA hypomethylating agent 5-aza-2'
      deoxycytidine (5-aza-CdR) to improve the effectiveness of immunotherapeutic
      approaches against melanocyte differentiation antigens. EXPERIMENTAL DESIGN: The
      effect of 5-aza-CdR on the constitutive expression of gp100 was investigated in
      11 human melanoma cell lines by real-time reverse transcription-PCR and indirect
      immunofluorescence (IIF) analyses. 5-aza-CdR-mediated changes in the levels of
      expression of human leukocyte antigen (HLA) class I antigens and HLA-A2
      allospecificity, intercellular adhesion molecule-1 (ICAM-1), and leukocyte
      function-associated antigen-3 were investigated by IIF analysis on melanoma cells
      under study. The recognition of gp100-positive Mel 275 melanoma cells, treated or
      not with 5-aza-CdR, by HLA-A2-restricted gp100((209-217))-specific CTL was
      investigated by (51)Cr-release assays, IFN-gamma release and IFN-gamma ELISPOT
      assays. RESULTS: The constitutive expression of gp100 was not affected by 5-aza
      CdR on all melanoma cells investigated. Compared with untreated cells, the
      exposure of Mel 275 melanoma cells to 5-aza-CdR significantly (P < 0.05) up
      regulated their expression of HLA class I antigens and of ICAM-1. These
      phenotypic changes significantly (P < 0.05) increased the lysis of 5-aza-CdR
      treated Mel 275 melanoma cells by gp100-specific CTL and increased their IFN
      gamma release. 5-aza-CdR treatment of Mel 275 cells also induced a higher number
      of gp100-specific CTL to secrete IFN-gamma. CONCLUSIONS: Treatment with 5-aza-CdR
      improves the recognition of melanoma cells by gp100-specific CTL through the up
      regulation of HLA class I antigens expression; ICAM-1 also contributes to this
      phenomenon. These findings highlight a broader range of therapeutic implications
      of 5-aza-CdR when used in association with active or adoptive immunotherapeutic
      approaches against a variety of melanoma-associated antigens.

PMID- 17545541
TI  - Overexpression of Clostridium perfringens enterotoxin receptors claudin-3 and
      claudin-4 in uterine carcinosarcomas.
AB  - PURPOSE: To evaluate the expression levels of claudin-3 and claudin-4, the low-
      and high-affinity receptors, respectively, for the cytotoxic Clostridium
      perfringens enterotoxin (CPE) in uterine carcinosarcomas and explore the
      potential for targeting these receptors in the treatment of this aggressive
      uterine tumor. EXPERIMENTAL DESIGN: We analyzed claudin-3 and claudin-4 receptor
      expression at mRNA and protein levels in flash frozen and formalin-fixed,
      paraffin-embedded carcinosarcoma specimens. Recombinant CPE was used as a novel
      therapy against chemotherapy-resistant carcinosarcoma cell lines in vitro. The
      therapeutic effect of sublethal doses of CPE was studied in severe combined
      immunodeficient mouse xenografts harboring large s.c. carcinosarcomas. RESULTS:
      All flash-frozen carcinosarcoma biopsies (12 of 12) and short-term carcinosarcoma
      cell lines evaluated overexpressed claudin-3 and claudin-4 by quantitative
      reverse transcription-PCR. Membranous immunoreactivity for claudin-4 protein
      expression was documented in 80% (20 of 25) of primary tumors and 100% (6 of 6)
      of the metastatic carcinosarcomas, whereas negligible staining was found in
      normal endometrial cells. Regardless of their resistance to chemotherapeutic
      agents, all short-term carcinosarcoma cell lines tested died within 1 h of
      exposure to 3.3 microg/mL of CPE in vitro. Intratumoral injections of well
      tolerated doses of CPE in large s.c. carcinosarcoma xenografts led to large areas
      of tumor cell necrosis and tumor disappearance in all treated animals.
      CONCLUSIONS: Claudin-3 and claudin-4 receptors are highly overexpressed in
      carcinosarcoma. These proteins may offer promising targets for the use of CPE as
      a novel type-specific therapy against this biologically aggressive variant of
      endometrial cancer.

PMID- 17545542
TI  - Identification and characterization of T-cell epitopes deduced from RGS5, a novel
      broadly expressed tumor antigen.
AB  - PURPOSE: Identification of tumor-associated antigens and advances in tumor
      immunology resulted in the development of vaccination strategies to treat
      patients with malignant diseases. In a novel experimental approach that combined
      comparative mRNA expression analysis of defined cell types with the
      characterization of MHC ligands by mass spectrometry, we found that regulator of
      G protein signaling 5 (RGS5) is extensively up-regulated in a broad variety of
      malignant cells, and we identified two HLA-A2- and HLA-A3-binding peptides
      derived from the RGS5 protein. Interestingly, RGS5 was recently shown to be
      involved in tumor angiogenesis. EXPERIMENTAL DESIGN: We used monocyte-derived
      dendritic cells pulsed with these novel antigenic peptides or transfected with
      RGS5-mRNA for the in vitro induction of CTLs, generated from healthy donors, to
      analyze the presentation of RGS5-deduced epitopes by malignant cells. RESULTS:
      The generated CTL lines elicited an antigen-specific and HLA-restricted cytolytic
      activity against tumor cells endogenously expressing the RGS5 protein.
      Furthermore, we were able to induce RGS5-specific CTLs using peripheral blood
      mononuclear cells from a patient with acute myeloid leukemia capable of
      recognizing the autologous leukemic blasts while sparing nonmalignant cells.
      CONCLUSIONS: These results indicate that the RGS5 peptides represent interesting
      candidates for the development of cancer vaccines designed to target malignant
      cells and tumor vessels.

PMID- 17545543
TI  - In vivo therapeutic synergism of anti-epidermal growth factor receptor and anti
      HER2 monoclonal antibodies against pancreatic carcinomas.
AB  - PURPOSE: Pancreatic carcinoma is highly resistant to therapy. Epidermal growth
      factor receptor (EGFR) and HER2 have been reported to be both dysregulated in
      this cancer. To evaluate the in vivo effect of binding both EGFR and HER2 with
      two therapeutic humanized monoclonal antibodies (mAb), we treated human
      pancreatic carcinoma xenografts, expressing high EGFR and low HER2 levels.
      EXPERIMENTAL DESIGN: Nude mice, bearing xenografts of BxPC-3 or MiaPaCa-2 human
      pancreatic carcinoma cell lines, were injected twice weekly for 4 weeks with
      different doses of anti-EGFR (matuzumab) and anti-HER2 (trastuzumab) mAbs either
      alone or in combination. The effect of the two mAbs, on HER receptor
      phosphorylation, was also studied in vitro by Western blot analysis. RESULTS: The
      combined mAb treatment significantly inhibited tumor progression of the BxPC-3
      xenografts compared with single mAb injection (P = 0.006) or no treatment (P =
      0.0004) and specifically induced some complete remissions. The two mAbs had more
      antitumor effect than 4-fold greater doses of each mAb. The significant
      synergistic effect of the two mAbs was confirmed on the MiaPaCa-2 xenograft and
      on another type of carcinoma, SK-OV-3 ovarian carcinoma xenografts. In vitro, the
      cooperative effect of the two mAbs was associated with a decrease in EGFR and
      HER2 receptor phosphorylation. CONCLUSIONS: Anti-HER2 mAb has a synergistic
      therapeutic effect when combined with an anti-EGFR mAb on pancreatic carcinomas
      with low HER2 expression. These observations may open the way to the use of these
      two mAbs in a large panel of carcinomas expressing different levels of the two
      HER receptors.

PMID- 17545544
TI  - Sorafenib inhibits imatinib-resistant KIT and platelet-derived growth factor
      receptor beta gatekeeper mutants.
AB  - PURPOSE: Targeting of KIT and platelet-derived growth factor receptor (PDGFR)
      tyrosine kinases by imatinib is an effective anticancer strategy. However,
      mutations of the gatekeeper residue (T670 in KIT and T681 in PDGFRbeta) render
      the two kinases resistant to imatinib. The aim of this study was to evaluate
      whether sorafenib (BAY 43-9006), a multitargeted ATP-competitive inhibitor of KIT
      and PDGFR, was active against imatinib-resistant KIT and PDGFRbeta kinases.
      EXPERIMENTAL DESIGN: We used in vitro kinase assays and immunoblot with
      phosphospecific antibodies to determine the activity of sorafenib on KIT and
      PDGFRbeta kinases. We also exploited reporter luciferase assays to measure the
      effects of sorafenib on KIT and PDGFRbeta downstream signaling events. The
      activity of sorafenib on interleukin-3-independent proliferation of Ba/F3 cells
      expressing oncogenic KIT or its imatinib-resistant T670I mutant was also tested.
      RESULTS: Sorafenib efficiently inhibited gatekeeper mutants of KIT and PDGFRbeta
      (IC(50) for KIT T670I, 60 nmol/L; IC(50) for PDGFRbeta T681I, 110 nmol/L).
      Instead, it was less active against activation loop mutants of the two receptors
      (IC(50) for KIT D816V, 3.8 micromol/L; IC(50) for PDGFRbeta D850V, 1.17
      micromol/L) that are also imatinib-resistant. Sorafenib blocked receptor
      autophosphorylation and signaling of KIT and PDGFRbeta gatekeeper mutants in
      intact cells as well as activation of AP1-responsive and cyclin D1 gene
      promoters, respectively. Finally, the compound inhibited KIT-dependent
      proliferation of Ba/F3 cells expressing the oncogenic KIT mutant carrying the
      T670I mutation. CONCLUSIONS: Sorafenib might be a promising anticancer agent for
      patients carrying KIT and PDGFRbeta gatekeeper mutations.

PMID- 17545546
TI  - Inhibition of p53-murine double minute 2 interaction by nutlin-3A stabilizes p53
      and induces cell cycle arrest and apoptosis in Hodgkin lymphoma.
AB  - PURPOSE: p53 is frequently expressed but rarely mutated in Hodgkin and Reed
      Sternberg (HRS) cells of Hodgkin's lymphoma (HL). p53 protein levels are
      regulated by murine double minute 2 (MDM2) through a well-established
      autoregulatory feedback loop. In this study, we investigated the effects of
      nutlin-3A, a recently developed small molecule that antagonizes MDM2 and disrupts
      the p53-MDM2 interaction, on p53-dependent cell cycle arrest and apoptosis in
      cultured HRS cells. EXPERIMENTAL DESIGN: HL cell lines carrying wild-type (wt) or
      mutated p53 gene were treated with the potent MDM2 inhibitor nutlin-3A or a 150
      fold less active enantiomer, nutlin-3B. RESULTS: We show that nutlin-3A, but not
      nutlin-3B, stabilizes p53 in cultured HRS cells carrying wt p53 gene resulting in
      p53-dependent cell cycle arrest and apoptosis. Cell cycle arrest was associated
      with up-regulation of the cyclin-dependent kinase inhibitor p21. Nutlin-3A
      induced apoptotic cell death was accompanied by Bax and Puma up-regulation and
      caspase-3 cleavage and was abrogated, in part, by inhibition of caspase-9 and
      caspase-3 activity. By contrast, no effects on cell cycle or apoptosis were found
      in HL cell lines harboring mutated p53 gene. Furthermore, combined treatment with
      nutlin-3A and doxorubicin revealed enhanced cytotoxicity in HRS cells with wt p53
      gene. Blocking of nuclear export by leptomycin B, or inhibition of proteasome by
      MG132, stabilized p53 at a level comparable with that of nutlin-3A treatment in
      HRS cells with wt p53. CONCLUSIONS: These data suggest that nutlin-3A stabilized
      p53 by preventing MDM2-mediated p53 degradation in HRS cells. wt p53
      stabilization and activation by nutlin-3A may be a novel therapeutic approach for
      patients with HL.

PMID- 17545545
TI  - Mifepristone inhibits ovarian cancer cell growth in vitro and in vivo.
AB  - PURPOSE: These studies were designed to determine whether the synthetic steroid
      mifepristone inhibits ovarian cancer growth in vitro and in vivo and the
      molecular mechanisms involved. EXPERIMENTAL DESIGN: The effect of mifepristone on
      ovarian cancer cell growth in vitro was studied in ovarian cancer cell lines of
      different genetic backgrounds (SK-OV-3, Caov-3, OV2008, and IGROV-1). In
      addition, the growth inhibition capacity of mifepristone on ovarian carcinoma
      xenografts was tested in nude mice. RESULTS: Mifepristone inhibited ovarian
      cancer cell proliferation in a dose- and time-dependent manner. The cytostatic
      effect of mifepristone was confirmed in a clonogenic survival assay and was not
      linked to loss of viability. Mifepristone blocked DNA synthesis, arrested the
      cell cycle at the G(1)-S transition, up-regulated cyclin-dependent kinase (cdk)
      inhibitors p21(cip1)and p27(kip1), down-regulated transcription factor E2F1,
      decreased expression of the E2F1-regulated genes cdk1 (cdc2) and cyclin A, and
      modestly decreased cdk2 and cyclin E levels. The abrupt arrest in cell growth
      induced by mifepristone correlated with reduced cdk2 activity, increased
      association of cdk2 with p21(cip1) and p27(kip1), increased nuclear localization
      of the cdk inhibitors, and reduced nuclear abundance of cdk2 and cyclin E. In
      vivo, mifepristone significantly delayed the growth of ovarian carcinoma
      xenografts in a dose-dependent manner and without apparent toxic effects for the
      animals. CONCLUSIONS: These preclinical studies show that mifepristone is
      effective as a single agent in vitro and in vivo, inhibiting the growth of human
      epithelial ovarian cancer cells. Mifepristone markedly reduces cdk2 activity
      likely due to increased association of cdk2 with the cdk inhibitors p21(cip1) and
      p27(kip1) and reduced nuclear cdk2/cyclin E complex availability. Acting as a
      cytostatic agent, mifepristone promises to be of translational significance in
      ovarian cancer therapeutics.

PMID- 17545547
TI  - The antitumor agent imexon activates antioxidant gene expression: evidence for an
      oxidative stress response.
AB  - PURPOSE: The aim of this study was to identify biomarkers that may be predictive
      for the clinical activity of the redox-active antitumor agent imexon.
      EXPERIMENTAL DESIGN: cDNA microarray and quantitative real-time PCR were used to
      identify global changes in gene expression in peripheral blood mononuclear cells
      (PBMC) collected from patients treated with imexon during a phase I trial.
      Electrophoretic mobility shift assays and Western blot analysis were done using
      the RPMI8226 myeloma cell line grown in vitro and PBMCs treated ex vivo to
      investigate the molecular mechanism responsible for these gene changes. RESULTS:
      Both cDNA microarray and quantitative real-time PCR showed the up-regulation of
      many antioxidant genes, including thioredoxin reductase-1, glutaredoxin-2, and
      peroxiredoxin-3 in PBMCs collected from patients treated with imexon. Studies in
      PBMCs treated ex vivo and RPMI8226 myeloma cells showed that imexon increased
      binding to the activator protein-1 consensus sequence measured by electrophoretic
      mobility shift assay. Supershift analysis showed that the majority of the
      activator protein-1 DNA binding activity was c-Jun, with minor contribution of
      Jun-D. Nuclear translocation of the nuclear factor (erythroid-derived 1)-like 2
      transcription factor and its binding to the antioxidant response element was also
      increased after imexon treatment, which correlated with an increase in the
      message levels for nuclear factor (erythroid-derived 1)-like 2/antioxidant
      response element-regulated antioxidant genes. CONCLUSIONS: Together, these
      results show that a predominant biological effect of imexon is a change in redox
      state that can be detected in surrogate normal tissues as increased redox
      sensitive transcription factor binding and increased antioxidant gene expression.

PMID- 17545548
TI  - Scheduling of radiation with angiogenesis inhibitors anginex and Avastin improves
      therapeutic outcome via vessel normalization.
AB  - PURPOSE: To test whether a direct antiangiogenic peptide (anginex) and a vascular
      endothelial growth factor antibody (bevacizumab, Avastin) can transiently
      normalize vasculature within tumors to improve oxygen delivery, alleviate
      hypoxia, and increase the effect of radiation therapy. EXPERIMENTAL DESIGN: Tumor
      oxygenation levels, microvessel density and pericyte coverage were monitored in
      three different solid tumor models (xenograft human ovarian carcinoma MA148,
      murine melanoma B16F10, and murine breast carcinoma SCK) in mice. Multiple
      treatment schedules were tested in these models to assess the influence on the
      effect of radiation therapy. RESULTS: In all three tumor models, we found that
      tumor oxygenation levels, monitored daily in real time, were increased during the
      first 4 days of treatment with both anginex and bevacizumab. From treatment day 5
      onward, tumor oxygenation in treated mice decreased significantly to below that
      in control mice. This "tumor oxygenation window" occurred in all three tumor
      models varying in origin and growth rate. Moreover, during the treatment period,
      tumor microvessel density decreased and pericyte coverage of vessels increased,
      supporting the idea of vessel normalization. We also found that the transient
      modulation of tumor physiology caused by either antiangiogenic therapy improved
      the effect of radiation treatment. Tumor growth delay was enhanced when single
      dose or fractionated radiotherapy was initiated within the tumor oxygenation
      window as compared with other treatment schedules. CONCLUSIONS: The results are
      of immediate translational importance because the clinical benefits of
      bevacizumab therapy might be increased by more precise treatment scheduling to
      ensure radiation is given during periods of peak radiosensitivity. The oxygen
      elevation in tumors by non-growth factor-mediated peptide anginex suggests that
      vessel normalization might be a general phenomenon of agents directed at
      disrupting the tumor vasculature by a variety of mechanisms.

PMID- 17545549
TI  - Bortezomib sensitizes primary human astrocytoma cells of WHO grades I to IV for
      tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis.
AB  - PURPOSE: Malignant gliomas are the most aggressive human brain tumors without any
      curative treatment. The antitumor effect of tumor necrosis factor-related
      apoptosis-inducing ligand (TRAIL) in gliomas has thus far only been thoroughly
      established in tumor cell lines. In the present study, we investigated the
      therapeutic potential of TRAIL in primary human glioma cells. EXPERIMENTAL
      DESIGN: We isolated primary tumor cells from 13 astrocytoma and oligoastrocytoma
      patients of all four WHO grades of malignancy and compared the levels of TRAIL
      induced apoptosis induction, long-term tumor cell survival, caspase, and caspase
      target cleavage. RESULTS: We established a stable culture model for isolated
      primary human glioma cells. In contrast to cell lines, isolated primary tumor
      cells from all investigated glioma patients were highly TRAIL resistant.
      Regardless of the tumor heterogeneity, cotreatment with the proteasome inhibitor
      bortezomib efficiently sensitized all primary glioma samples for TRAIL-induced
      apoptosis and tremendously reduced their clonogenic survival. Due to the
      pleiotropic effect of bortezomib-enhanced TRAIL DISC formation upon TRAIL
      triggering, down-regulation of cFLIP(L) and activation of the intrinsic apoptosis
      pathway seem to cooperatively contribute to the antitumor effect of
      bortezomib/TRAIL cotreatment. CONCLUSION: TRAIL sensitivity of tumor cell lines
      is not a reliable predictor for the behavior of primary tumor cells. The
      widespread TRAIL resistance in primary glioma cells described here questions the
      therapeutic clinical benefit of TRAIL as a monotherapeutic agent. Overcoming
      TRAIL resistance by bortezomib cotreatment might, however, provide a powerful
      therapeutic option for glioma patients.

PMID- 17545550
TI  - Schedule-dependent cytotoxic synergism of pemetrexed and erlotinib in human non
      small cell lung cancer cells.
AB  - PURPOSE: This study was undertaken to select the optimal combination schedule of
      erlotinib and pemetrexed for the treatment of relapsed non-small cell lung cancer
      (NSCLC) using a panel of human NSCLC lines. EXPERIMENTAL DESIGN: Human NSCLC cell
      lines, with variable expression of the known molecular determinants of erlotinib
      sensitivity, were exposed to pemetrexed and erlotinib using different schedules.
      Antitumor effect was measured by growth inhibition by cell count and 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, cell cycle
      distribution and apoptosis by flow cytometry, and expression of cell cycle
      mediators by immunoblots. The cytotoxic interaction between pemetrexed and
      erlotinib (i.e., synergistic, additive, or antagonistic) was determined by median
      effect analysis. RESULTS: When cells were exposed to concurrent pemetrexed and
      erlotinib or sequential pemetrexed followed by erlotinib, cytotoxic synergism was
      observed in both erlotinib-sensitive and erlotinib-resistant human NSCLC cell
      lines. This was independent of the mutation status of epidermal growth factor
      receptor or K-Ras genes. Synergism was associated with a combination of cell
      cycle effects from both agents. In contrast, exposure of cells to erlotinib
      followed by pemetrexed was mostly antagonistic in erlotinib-sensitive cells and
      additive at best in erlotinib-resistant cells. Antagonism was associated with
      erlotinib-induced G(1)-phase blockade of erlotinib-sensitive cells, which
      protects cells from pemetrexed cytotoxicity. Pemetrexed induced an epidermal
      growth factor receptor-mediated activation of the phosphatidylinositol 3
      kinase/AKT pathway, which was inhibited by erlotinib and a specific
      phosphatidylinositol 3-kinase inhibitor, LY294002. CONCLUSIONS: The combination
      of pemetrexed and erlotinib is synergistic in NSCLC in vitro if exposure to
      erlotinib before pemetrexed is avoided, particularly in tumors that are sensitive
      to erlotinib. Based on these findings, a randomized phase II study comparing the
      progression-free survival between an intermittent combination of erlotinib and
      pemetrexed (experimental arm) and pemetrexed alone (control arm) in patients with
      relapsing NSCLC has been initiated.

PMID- 17545551
TI  - Curcumin inhibits tumor growth and angiogenesis in ovarian carcinoma by targeting
      the nuclear factor-kappaB pathway.
AB  - PURPOSE: Curcumin, a component of turmeric, has been shown to suppress
      inflammation and angiogenesis largely by inhibiting the transcription factor
      nuclear factor-kappaB (NF-kappaB). This study evaluates the effects of curcumin
      on ovarian cancer growth using an orthotopic murine model of ovarian cancer.
      EXPERIMENTAL DESIGN: In vitro and in vivo experiments of curcumin with and
      without docetaxel were done using human ovarian cancer cell lines SKOV3ip1,
      HeyA8, and HeyA8-MDR in athymic mice. NF-kappaB modulation was ascertained using
      electrophoretic mobility shift assay. Evaluation of angiogenic cytokines,
      cellular proliferation (proliferating cell nuclear antigen), angiogenesis (CD31),
      and apoptosis (terminal deoxynucleotidyl transferase-mediated dUTP nick end
      labeling) was done using immunohistochemical analyses. RESULTS: Curcumin
      inhibited inducible NF-kappaB activation and suppressed proliferation in vitro.
      In vivo dose-finding experiments revealed that 500 mg/kg orally was the optimal
      dose needed to suppress NF-kappaB and signal transducers and activators of
      transcription 3 activation and decrease angiogenic cytokine expression. In the
      SKOV3ip1 and HeyA8 in vivo models, curcumin alone resulted in 49% (P = 0.08) and
      55% (P = 0.01) reductions in mean tumor growth compared with controls, whereas
      when combined with docetaxel elicited 96% (P < 0.001) and 77% reductions in mean
      tumor growth compared with controls. In mice with multidrug-resistant HeyA8-MDR
      tumors, treatment with curcumin alone and combined with docetaxel resulted in
      significant 47% and 58% reductions in tumor growth, respectively (P = 0.05). In
      SKOV3ip1 and HeyA8 tumors, curcumin alone and with docetaxel decreased both
      proliferation (P < 0.001) and microvessel density (P < 0.001) and increased tumor
      cell apoptosis (P < 0.05). CONCLUSIONS: Based on significant efficacy in
      preclinical models, curcumin-based therapies may be attractive in patients with
      ovarian carcinoma.

PMID- 17545553
TI  - The epidermal growth factor receptor D761Y mutation and effect of tyrosine kinase
      inhibitor.

PMID- 17545554
TI  - Therapeutic role of bisphosphonate and radiation combination in the management of
      myeloma bone disease.

PMID- 17545555
TI  - Traumatic brain injury: assessment, resuscitation and early management.
AB  - This review examines the evidence base for the early management of head-injured
      patients. Traumatic brain injury (TBI) is common, carries a high morbidity and
      mortality, and has no specific treatment. The pathology of head injury is
      increasingly well understood. Mechanical forces result in shearing and
      compression of neuronal and vascular tissue at the time of impact. A series of
      pathological events may then ensue leading to further brain injury. This
      secondary injury may be amenable to intervention and is worsened by secondary
      physiological insults. Various risk factors for poor outcome after TBI have been
      identified. Most of these are fixed at the time of injury such as age, gender,
      mechanism of injury, and presenting signs (Glasgow Coma Scale and pupillary
      signs), but some such as hypotension and hypoxia are potential areas for medical
      intervention. There is very little evidence positively in favour of any
      treatments or packages of early care; however, prompt, specialist neurocritical
      care is associated with improved outcome. Various drugs that target specific
      pathways in the pathophysiology of brain injury have been the subject of animal
      and human research, but, to date, none has been proved to be successful in
      improving outcome.

PMID- 17545556
TI  - Novel deletions of 14q11.2 associated with developmental delay, cognitive
      impairment and similar minor anomalies in three children.
AB  - METHODS AND RESULTS: We identified de novo submicroscopic chromosome 14q11.2
      deletions in two children with idiopathic developmental delay and cognitive
      impairment. Vancouver patient 5566 has a approximately 200 kb deletion and
      Vancouver patient 8326 has a approximately 1.6 Mb deletion. The Database of
      Chromosomal Imbalance and Phenotype in Humans using Ensembl Resources (DECIPHER)
      revealed a third patient with idiopathic developmental delay and cognitive
      impairment, DECIPHER patient 126, who has a approximately 1.1 Mb deletion of
      14q11.2. The deletion of patient 5566 overlaps that of patient 126 and both of
      these deletions lie entirely within that of patient 8326. All three children have
      similar dysmorphic features, including widely-spaced eyes, short nose with flat
      nasal bridge, long philtrum, prominent Cupid's bow of the upper lip, full lower
      lip and similar auricular anomalies. CONCLUSION: The minimal common deletion
      region on chromosome 14q11.2 is only approximately 35 kb (from 20.897 to 20.932,
      University of California at Santa Cruz (UCSC) Genome Browser; build hg18, March
      2006) and includes only two genes, SUPT16H and CHD8, which are good candidate
      genes for the phenotypes. The non-recurrent breakpoints of these patients, the
      presence of normal copy number variants in the region and the local genomic
      structure support the notion that this region has reduced stability.

PMID- 17545558
TI  - Fatal circumstances of human herpesvirus 6 infection: transcriptosome data
      analysis suggests caution in implicating HHV-6 in the cause of death.

PMID- 17545557
TI  - Stability of the m.8993T->G mtDNA mutation load during human embryofetal
      development has implications for the feasibility of prenatal diagnosis in NARP
      syndrome.
AB  - BACKGROUND: Mitochondrial DNA (mtDNA) mutations cause a wide range of serious
      genetic diseases with maternal inheritance. Because of the high transmission risk
      and the absence of therapy in these disorders, at-risk couples often ask for
      prenatal diagnosis (PND). However, because heteroplasmy load (coexistence of
      mutant and wild-type mtDNA) may vary among tissues and with time, the possibility
      that a single fetal sample may not reflect the whole neonate impedes prenatal
      diagnosis of mtDNA diseases. METHODS: We performed 13 prenatal diagnoses for the
      NARP (neurogenic weakness, ataxia, retinitis pigmentosa) m.8993T-->G mtDNA
      mutation (p.Leu156Arg) in the ATP synthase subunit 6 gene. Analyses were
      performed on chorionic villous (CVS) and/or amniocyte samples carried out at
      various stages of pregnancy, using a method enabling quantification of low DNA
      amounts. RESULTS: Maternal mutant loads ranged from 0 to 75% in blood and had no
      predictive value for the fetus status, except for women with no detectable mutant
      DNA, whose fetuses were consistently mutation-free. In 8/13 PND, mutant load was
      <30%. These children are healthy at 2-7 years of age. In 5/13 PND, mutant load
      ranged from 65 to 100%, and parents preferred to terminate the pregnancies (15-22
      weeks of gestation). Single-cell analysis of 20 trophoblastic cells and 21
      amniocytes isolated from two affected fetuses found an average mutant load close
      to the overall CVS and amniocyte mutant load, despite striking intercellular
      variation. The m.8993T-->G mutant loads, assessed in 7, 17, 11, and 5 different
      tissues from 4 terminations, respectively, were identical in all tissues from a
      given individual (mean (SD) 78 (1.2)%, 91 (0.7)%, 74 (2)%, and 63 (1.6)% for the
      4 fetuses, respectively). CONCLUSIONS: Our results indicate that the
      placental/amniotic mutant loads do reflect the NARP mutant mtDNA load in the
      whole fetus, even when the sample amount is small, and suggest that heteroplasmy
      level remains stable during pregnancy, at least after 10 weeks of gestation.
      Although these data establish the feasibility of PND for this mutation, assessing
      more precisely the correlation between mutant load and disease severity should
      further help in interpreting PND results.

PMID- 17545559
TI  - Malignant melanoma of the ciliary body presenting as extraocular metastasis in
      the temporalis muscle.

PMID- 17545560
TI  - Morphological diagnosis of urothelial neoplasms.
AB  - The morphological classification and diagnosis of bladder neoplasms is
      summarised, with specific focus on histological typing, grading and staging. Four
      diagnostic categories are described on the basis of the pattern of growth of the
      urothelial lesions and tumours (flat, exophytic or papillary, endophytic, and
      invasive). The WHO 2004 classification is currently used. However, the WHO 1973
      classification is still considered by many urologists and oncologists as the
      international standard in patient management.

PMID- 17545561
TI  - Antinuclear antibody is associated with a more advanced fibrosis and lower RNA
      levels of hepatitis C virus in patients with chronic hepatitis C.
AB  - AIMS: Positive serum antinuclear antibody (ANA) is present in a number of
      patients with chronic hepatitis C virus (HCV) infection. This study aimed to
      evaluate the prevalence of ANA in patients with chronic hepatitis C (CHC) and to
      elucidate its clinical implications in virological and histological
      characteristics of CHC infection. METHODS: A total of 614 CHC patients were
      enrolled in this prospective, hospital-based study. The serum levels of aspartate
      aminotransferase, alanine aminotransferase and ANA, and HCV genotype, HCV RNA
      level, and histological activity index scores for liver histopathology, were
      determined. RESULTS: The prevalence of positive ANA (titre >1:40) was 35.0%.
      Women had a significantly higher prevalence than men (41.2 vs 31.0%; p = 0.012).
      Patients positive for ANA were significantly older (mean (SD), 53.7 (10.5) vs
      49.7 (11.3) years; p<0.001) and had higher mean (SD) alanine aminotransferase
      levels (186.9 (178.8) vs 155.50 (113.5) IU/l; p<0.001) and lower mean (SD) HCV
      RNA levels (5.2 (0.9) vs 5.4 (1.0) log IU/ml; p = 0.048) than those without ANA.
      Among 447 patients undergoing liver biopsy, those positive for ANA had a
      significantly higher mean (SD) fibrosis score (2.0 (1.3) vs 1.5 (1.1); p<0.001)
      and a higher frequency of F3-4 (69/187, 36.9% vs 50/260, 19.2%; p<0.001) than
      those negative for ANA. Multivariate logistic regression analyses showed that
      advanced fibrosis, lower HCV RNA levels and age were significant factors related
      to positive ANA. CONCLUSION: ANA is associated with a more advanced liver
      fibrosis and lower serum HCV RNA level in patients with CHC.

PMID- 17545562
TI  - A comparative study of the quality of DNA obtained from fresh frozen and formalin
      fixed decalcified paraffin-embedded bone marrow trephine biopsy specimens using
      two different methods.
AB  - BACKGROUND: Given its prognostic value, there is renewed interest in molecular
      staging in non-Hodgkin's lymphoma (NHL) using immunoglobulin heavy and light
      chain (IgH, IgL) gene rearrangements. AIMS: To compare the efficiency of DNA
      amplification from fresh frozen and formalin-fixed decalcified paraffin-embedded
      (FFDPE) bone marrow trephines for use in molecular staging using two methods.
      METHODS: After manually extracting DNA from 13 FFDPE and 14 fresh frozen trephine
      biopsy specimens, two methods were used to test for amplifiability: use of the
      amplification control master mix supplied in the In Vivo Scribe immunoglobulin
      heavy chain (IgH) clonality kit, which creates 5 amplicons between 96-600 base
      pairs (bp); and real-time amplification of the beta-globin gene. RESULTS: Using
      the first method, the mean maximum length of amplicons generated from FFDPE
      trephines was statistically lower at 300 bp compared to fresh frozen samples, all
      of which generated amplicons up to 600 bp in size (p<0.001). Real-time
      amplification of the beta-globin gene showed that the mean crossing threshold of
      fresh frozen samples was statistically lower than that of FFDPE samples (23.48
      (95% CI 22.47 to 24.48) vs 33.64 (95% CI 32.15 to 35.12); p<0.001). CONCLUSIONS:
      Although amplifiable DNA can be extracted from both fresh-frozen and FFDPE
      trephine samples for IgH/IgL analysis, freshly frozen specimens are superior as a
      source of template DNA, especially for higher base pair PCR products.

PMID- 17545563
TI  - Human cell growth requires a functional cytoplasmic exosome, which is involved in
      various mRNA decay pathways.
AB  - The human exosome is a 3'-5' exoribonuclease complex that functions both in the
      nucleus and in the cytoplasm to either degrade or process RNA. Little is known
      yet about potential differences among core exosome complexes in these different
      cellular compartments and the roles of the individual subunits in maintaining a
      stable and functional complex. Glycerol gradient sedimentation analyses indicated
      that a significant subset of nuclear exosomes is present in much larger complexes
      (60-80S) than the cytoplasmic exosomes ( approximately 10S). Interestingly, siRNA
      mediated knock-down experiments indicated that the cytoplasmic exosome is down
      regulated much more efficiently than the nuclear exosome. In addition, we
      observed that knock-down of hRrp41p or hRrp4p but not PM/Scl-100 or PM/Scl-75
      leads to codepletion of other subunits. Nevertheless, PM/Scl-100 and PM/Scl-75
      are required to maintain normal levels of three different mRNA reporters: a wild
      type beta-globin mRNA, a beta-globin mRNA containing an AU-rich (ARE) instability
      element, and a beta-globin mRNA bearing a premature termination codon (PTC). The
      increased levels of ARE- and the PTC-containing mRNAs upon down-regulation of the
      different exosome subunits, in particular PM/Scl-100, appeared to be due to
      decreased turnover rates. These results indicate that, although not required for
      exosome stability, PM/Scl-100 and PM/Scl-75 are involved in mRNA degradation,
      either as essential subunits of a functional exosome complex or as exosome
      independent proteins.

PMID- 17545564
TI  - Healthy Cities, local environmental action and climate change.
AB  - This paper reports results of a study that explored the relationship between the
      local environmental actions of Healthy Cities programs and the adverse health
      impacts of climate change. The analysis is primarily based on a limited
      literature review of climate change and health, with particular attention to the
      relationships between Healthy Cities and climate change, and on documentary
      analysis of information from organization reports and website content associated
      with Healthy Cities programs in Europe and Australia. Four semi-structured
      interviews with key people in two Healthy Cities programs in Europe and Australia
      were conducted to provide information to supplement and complement the published
      information and to verify theme identification. The main findings of this study
      are that, although there is no explicit connection between the local activities
      of Healthy Cities programs and the potential (or actual) adverse health impacts
      of climate change, Healthy Cities programs are involved in many local
      environmental actions and some of these actions, for example, those relating to
      improving air quality and reducing pollution, are linked implicitly to the health
      impacts of climate change. Through their local relationships and their
      participation in regional networks, Healthy Cities are able to make connections
      between local environmental actions and the health impacts of climate change.
      Furthermore, expanding Healthy Cities to include eco-social sustainability as a
      central aim not only has the potential to strengthen the links between local
      environmental actions and climate change, but also presents a relevant health
      development setting for exploring the social and environmental sustainability of
      cities.

PMID- 17545565
TI  - Impact of a multiple, IVF birth on post-partum mental health: a composite
      analysis.
AB  - BACKGROUND: This study explored the impact of a multiple IVF birth on maternal
      mental health in the early post-partum period. METHODS: A prospective study of
      207 women who had conceived following IVF treatment and followed up at 6 weeks
      post-partum. Mothers rated their mood using the Edinburgh postnatal depression
      scale (EPDS) and their baby's behaviour using the Unsettled and Irregular
      Behaviour scale. Mothers' emotional well-being was explored using theme analysis
      of semi-structured telephone interviews. RESULTS: Of the 175 (84.5%) followed up
      post-partum, 56 (32%) had a multiple birth (7 triplets, 49 twins). Nearly 16% of
      mothers in the multiple group scored>12 on the EPDS indicating clinically
      significant symptoms, which represented a 3-fold increased risk compared to
      mothers of singletons (Odds ratio=3.4, Confidence Interval=1.011-11.618,
      P=0.048). Unsettled and irregular infant behaviour was another independent risk
      factor. Qualitative analysis of interviews identified 12 themes. Mothers of
      multiples were more likely to express negative themes including 'tiredness'
      (P<0.01), 'feelings of stress/depression' (P<0.05) and 'questioning parenthood'
      (P<0.05). Mothers of singletons were more likely to be 'feeling wonderful',
      reflecting their delight in parenthood (P<0.05). CONCLUSIONS: Mothers of
      multiples are at increased risk of poorer emotional well-being. Clinicians should
      focus on the psychological benefits of a singleton birth.

PMID- 17545567
TI  - Health disparities and violence against women: why and how cultural and societal
      influences matter.
AB  - This article encourages readers to consider the cultural and societal influences
      that impact health and health disparities among women survivors of intimate
      partner violence (IPV). Health consequences caused by IPV are widely documented
      and broadly discussed. Connections between health disparities and IPV are also
      discussed as related to women of color. Cultural factors and societal influences
      are identified to provide the reader with greater awareness of how these issues
      intersect with and impact IPV. Finally, the implications for scientific research
      and practice are discussed to include considerations for stronger assessment
      tools, greater collaboration and community participation, determination of best
      practices, requirement of cultural competence, mandated accountability,
      encouragement of mentorship, increased funding for research, increased advocacy,
      and increased culturally competent media and health promotion campaigns.

PMID- 17545568
TI  - Intimate partner violence and the childbearing year: maternal and infant health
      consequences.
AB  - Intimate partner violence (IPV) against women is a significant public health
      problem with negative physical and mental health consequences. Pregnant women are
      not immune to IPV, and as many as 4% to 8% of all pregnant women are victims of
      partner violence. Among pregnant women, IPV has been associated with poor
      physical health outcomes such as increased sexually transmitted diseases, preterm
      labor, and low-birth-weight infants. This article focuses on the physical health
      consequences of IPV for mothers and their infants. The purpose of this review is
      therefore to examine timely research ranging from 2001 to 2006 on IPV during
      pregnancy, the morbidity and mortality risks for mothers and their infants, and
      the association between IPV and perinatal health disparities. It will also
      identify gaps in the published empirical literature and make recommendations for
      practice, policy, and research.

PMID- 17545569
TI  - Inflammation, cardiovascular disease, and metabolic syndrome as sequelae of
      violence against women: the role of depression, hostility, and sleep disturbance.
AB  - Women who experience violence are significantly more likely to have serious
      health problems above and beyond any injuries they might incur. The intriguing
      question is why this is so. In this article, the author describes how three
      sequelae of violence against women-depression, hostility, and sleep disturbance
      can increase the risk of disease. One possible mechanism by which these sequelae
      increase risk is by elevating levels of pro-inflammatory cytokines. These
      cytokines have an adaptive function in fighting infection and repairing injured
      tissues. However, chronically high levels of pro-inflammatory cytokines have been
      implicated in a wide range of diseases. The author focuses on two illnesses that
      have not received much attention in the violence against women (VAW) literature:
      cardiovascular disease and metabolic syndrome, the precursor to type 2 diabetes.
      Preliminary studies also suggest that treatments that can lower inflammation may
      be promising adjuncts for survivors of VAW.

PMID- 17545570
TI  - Pregnancy following partner rape: what we know and what we need to know.
AB  - Despite more than 30 years of research on violence against women and scores of
      publications on intimate partner violence during pregnancy and consequences for
      maternal and infant health, little is known about the incidence and outcomes of
      pregnancies that follow partner rape. The occurrence and consequences of partner
      rape and violence during pregnancy are reviewed as well as the one study
      identified on the characteristics and consequences of pregnancy following partner
      rape. Literature on unintended pregnancy and violence against women is also
      reviewed. Directions for future research are explored, including the need for
      studies that explore women's control of their sexuality within the context of
      intimate partner relationships, how and when to ask women about partner rape, and
      how to include males as the solution to ending rape.

PMID- 17545571
TI  - Pregnancy-associated violent deaths: the role of intimate partner violence.
AB  - This literature review examines intimate partner violence in relation to
      pregnancy-associated femicide and suicide. Empirical publications were eligible
      for review if they included information on intimate partner violence and examined
      females who were pregnant/postpartum and who were victims of femicide/attempted
      femicide and/or suicide/attempted suicide. Nine publications met the inclusion
      criteria and were reviewed. Results suggest that intimate partners perpetrate one
      to two-thirds of the pregnancy-associated femicides in the United States and
      that pregnant women make up 5% of urban intimate partner femicides. Intimate
      partner abuse during pregnancy appears to be a risk factor for severe intimate
      partner violence, including attempted/completed femicide. So little information
      exists concerning intimate partner violence in pregnancy-associated suicides that
      it is impossible to draw conclusions regarding this topic; however, a hospital
      based study suggests that intimate partner violence may be a risk factor for
      attempting suicide while pregnant. More research is needed concerning intimate
      partner pregnancy-associated femicide and suicide so that evidenced-based
      preventive/therapeutic interventions may be developed.

PMID- 17545572
TI  - Does physical intimate partner violence affect sexual health? A systematic
      review.
AB  - Forty years of published research (1966-2006) addressing physical intimate
      partner violence (IPV) and sexual health was reviewed (51 manuscripts) and
      synthesized to determine (a) those sexual health indicators for which sufficient
      evidence is available to suggest a causal association and (b) gaps in the
      literature for which additional careful research is needed to establish causality
      and explain mechanisms for these associations. Sexual health was defined as a
      continuum of indicators of gynecology and reproductive health. IPV was
      consistently associated with sexual risk taking, inconsistent condom use, or
      partner nonmonogamy (23 of 27 studies), having an unplanned pregnancy or induced
      abortion (13 of 16 studies), having a sexually transmitted infection (17 of 24
      studies), and sexual dysfunction (17 of 18 studies). A conceptual model was
      presented to guide further needed research addressing direct and indirect
      mechanisms by which physical, sexual, and psychological IPV affects sexual
      health.

PMID- 17545573
TI  - HIV/AIDS and intimate partner violence: intersecting women's health issues in the
      United States.
AB  - This article reviews 35 U.S. studies on the intersection of HIV and adult
      intimate partner violence (IPV). Most studies describe rates of IPV among women
      at risk or living with HIV/AIDS and identify correlates, using multiple types of
      convenience samples (e.g., women in methadone treatment, women in shelters or
      clinics), cross-sectional designs, and self-reported risk behaviors. HIV-positive
      women appear to experience any IPV at rates comparable to HIV-negative women from
      the same underlying populations; however, their abuse seems to be more frequent
      and more severe. The authors found only four relevant interventions and none
      addressed sexually transmitted HIV and partner violence risk reduction
      simultaneously. There is a critical need for research on (a) causal pathways and
      cumulative effects of the syndemic issues of violence, HIV, and substance abuse
      and (b) interventions that target IPV victims at risk for HIV, as well as HIV
      positive women who may be experiencing IPV.

PMID- 17545574
TI  - Screening for intimate partner violence in medical settings.
AB  - Intimate partner violence (IPV) is associated with negative health consequences.
      Universal screening for IPV offers many opportunities for successful
      intervention, yet this practice in medical settings is controversial. This
      article examines the potential impact of the U.S. Preventive Services Task Force
      (USPSTF) recommendations for IPV screening and the emerging literature supporting
      measurable health benefits resulting from screening interventions in medical
      settings. Several screening tools and methods of administration that have been
      evaluated in various clinical settings, with goals to increase their sensitivity
      and to determine a best method of administration, are reviewed in this article.
      Mandatory reporting is closely linked to screening practices and may influence
      healthcare worker practice and patient disclosure. Mandatory reporting studies
      are lacking and show variable physician compliance, victim acceptance, and scant
      outcome data. Informed consent prior to screening, explaining the process of
      mandatory reporting statutes and victim options should be evaluated to increase
      sensitivity of screening tools.

PMID- 17545575
TI  - Preparing the next generation of physicians: medical school and residency-based
      intimate partner violence curriculum and evaluation.
AB  - Medical schools and postgraduate residency programs have largely included
      intimate partner violence (IPV) in their curricula. There is presently
      disagreement on the optimal model for implementing such training and the amount
      of time to be devoted to IPV. There is considerable overlap in the general
      content and teaching methods that focus on enhancing medical knowledge,
      professional attitudes, and clinical skills for asking about and responding to
      patient reports of IPV. Curricular evaluations have generally supported the idea
      that training increases knowledge, attitudes, and skills. However, a number of
      methodological issues preclude firm conclusions. There is a need for more
      randomized, controlled studies, better quasi-experimental designs, posttraining
      follow-up intervals, and demonstrations of actual clinical behavioral competency.
      Despite the latter concerns, however, the future shows promise that the next
      generation of physicians will understand and accept IPV and its health effects on
      their patients as constituting an important health issue that they will
      comfortably address.

PMID- 17545576
TI  - Interactions between victims of intimate partner violence against women and the
      health care system: policy and practice implications.
AB  - Intimate partner violence (IPV) affects the use of health care by increasing the
      risk of poor health outcomes. IPV victims seek health services as often as others
      but are less likely to receive needed services, more likely to overuse services,
      and more likely to have a poor relationship with their health care provider. This
      stems from patient and provider barriers to care that are exacerbated by the lack
      of a clear and consistent health care system response to IPV. Most health care
      systems are not equipped to assist either victims or providers seeking to help
      victims. There are a few models of system-wide interventions, but these are not
      the current standard. A strong health policy framework is needed, but the
      decision of the U.S. Preventative Task Force not to recommend universal screening
      is a setback. Overall, there is limited progress in moving the health care system
      toward assisting IPV victims.

PMID- 17545578
TI  - Accurate quantitation of allele-specific expression patterns by analysis of DNA
      melting.
AB  - Epigenetic and genetic mechanisms can result in large differences in expression
      levels of the two alleles in a diploid organism. Furthermore, these differences
      may be critical to phenotypic variations among individuals. In this study, we
      present a novel procedure and algorithm to precisely and accurately quantitate
      the relative expression of each allele. This method uses the differential melting
      properties of DNAs differing at even a single base pair. By referring to the
      melting characteristics of the two pure alleles, the fractional contribution of
      the two alleles to any unknown mixture can be mathematically resolved. These
      methods are highly accurate and precise because each single melting reaction
      yields multiple data points for analysis. Finally, we discuss how this approach
      can be used more generally to accurately quantitate gene expression relative to
      known standards.

PMID- 17545579
TI  - Myc goes global: new tricks for an old oncogene.
AB  - Myc, a transcription factor commonly deregulated in tumorigenesis, is thought to
      mediate its diverse cellular effects by altering the expression of specific
      target genes. However, it has been difficult to gain a precise understanding of
      how Myc drives cancer because Myc acts rather weakly at many of its target loci,
      and it has been reported to regulate as many as 10% to 15% of all cellular genes.
      A new perspective on this issue has been provided by a recent study that revealed
      Myc can regulate chromatin structure in a global fashion. These findings suggest
      actions for Myc that extend beyond the traditional concept of a targeted gene
      regulator.

PMID- 17545580
TI  - Tumor-associated macrophages press the angiogenic switch in breast cancer.
AB  - The development of a supportive vasculature is essential for tumor progression.
      In a mouse model of breast cancer, we found that tumor-associated macrophages
      that are recruited to the tumor just before malignant conversion are essential
      for the angiogenic switch. These findings establish a causal linkage to explain
      well-documented clinical correlations between macrophages, microvessel density,
      and poor prognosis in breast tumors.

PMID- 17545577
TI  - HIV integration site selection: analysis by massively parallel pyrosequencing
      reveals association with epigenetic modifications.
AB  - Integration of retroviral DNA into host cell DNA is a defining feature of
      retroviral replication. HIV integration is known to be favored in active
      transcription units, which promotes efficient transcription of the viral genes,
      but the molecular mechanisms responsible for targeting are not fully clarified.
      Here we used pyrosequencing to map 40,569 unique sites of HIV integration.
      Computational prediction of nucleosome positions in target DNA indicated that
      integration sites are periodically distributed on the nucleosome surface,
      consistent with favored integration into outward-facing DNA major grooves in
      chromatin. Analysis of integration site positions in the densely annotated ENCODE
      regions revealed a wealth of new associations between integration frequency and
      genomic features. Integration was particularly favored near transcription
      associated histone modifications, including H3 acetylation, H4 acetylation, and
      H3 K4 methylation, but was disfavored in regions rich in transcription-inhibiting
      modifications, which include H3 K27 trimethylation and DNA CpG methylation.
      Statistical modeling indicated that effects of histone modification on HIV
      integration were partially independent of other genomic features influencing
      integration. The pyrosequencing and bioinformatic methods described here should
      be useful for investigating many aspects of retroviral DNA integration.

PMID- 17545581
TI  - Mechanism and therapeutic reversal of immune suppression in cancer.

PMID- 17545582
TI  - Endothelial Akt signaling is rate-limiting for rapamycin inhibition of mouse
      mammary tumor progression.
AB  - Chronic activation of Akt signaling in the endothelium recapitulates the salient
      features of a tumor vasculature and can be inhibited by rapamycin, an inhibitor
      of mammalian target of rapamycin. This led to the hypothesis that the antitumor
      efficacy of rapamycin may be partially dependent on its ability to inhibit
      endothelial Akt signaling, making rapamycin an antiangiogenic agent and
      endothelial Akt pathway inhibitor. Dose-response studies with rapamycin showed
      that primary human endothelial cells and fibroblasts had a bimodal Akt response
      with effective reductions in phosphorylated Akt (pAkt) achieved at 10 ng/mL. In
      contrast, rapamycin increased pAkt levels in tumor cell lines. When tumor-bearing
      mice were treated with rapamycin doses comparable to those used clinically in
      transplant patients, we observed strong inhibition of mammary tumor growth. To
      test whether Akt activation in the endothelium was rate-limiting for this
      antitumor response, we engineered mouse mammary tumor virus-polyoma virus middle
      T antigen mice with endothelial cell-specific expression of constitutively
      activated Akt. We observed that the antitumor efficacy of rapamycin was reduced
      in the presence of elevated endothelial Akt activation. Just as we observed in
      MCF7 cells in vitro, rapamycin doses that were antiangiogenic resulted in
      increased pAkt levels in total mouse mammary tumor virus-polyoma virus middle T
      antigen tumor lysates, suggesting that tumor cells had an opposite Akt response
      following mammalian target of rapamycin inhibition compared with tumor
      endothelial cells. Together, these data support the hypothesis that endothelial
      Akt signaling in the tumor vasculature is an important target of the novel
      anticancer drug rapamycin.

PMID- 17545583
TI  - Human tumor xenografts recurring after radiotherapy are more sensitive to anti
      vascular endothelial growth factor receptor-2 treatment than treatment-naive
      tumors.
AB  - The effects of antiangiogenic therapy on tumors relapsing after irradiation are
      not known. To this end, we irradiated human tumors growing s.c. in nude mice with
      a single dose of 20 or 30 Gy. Compared with primary (treatment-naive) xenografts,
      the growth rate of recurrent tumors was 1.6-fold slower, which is consistent with
      the known "tumor bed effect." For similar size tumors, recurrences had fewer
      functional vessels, a reduced vessel coverage by perivascular cells, and were
      more necrotic. Placenta growth factor concentration was significantly lower in
      relapses, whereas vascular endothelial growth factor (VEGF) levels were similar
      between primary and recurrent tumors. On the other hand, fibrillar collagen
      deposition was significantly increased in recurrent tumors. This radiation
      induced fibrosis was partially responsible for the slower growth of recurrences;
      the i.t. injection of collagenase increased the growth rate of tumor relapses
      without affecting primary tumor growth. The mouse-specific VEGF receptor 2
      blocking antibody DC101 induced a 2.2-fold longer growth delay in recurrent
      tumors compared with treatment-naive tumors. DC101 significantly decreased the
      interstitial fluid pressure and did not change the functional vessel density and
      perivascular cell coverage in both tumor variants. Interestingly, DC101 induced a
      rapid (2 days after treatment initiation) and significant decrease in tumor cell
      proliferation in recurrent but not in primary tumors. Thus, our results show that
      the stromal compartment and the response to antiangionenic therapy of primary and
      in-field recurrent tumors are significantly different. Our findings suggest that
      antiangiogenic agents could be effective in the treatment of patients with
      relapses after radiotherapy.

PMID- 17545584
TI  - Mel-18 acts as a tumor suppressor by repressing Bmi-1 expression and down
      regulating Akt activity in breast cancer cells.
AB  - The Bmi-1 oncogene is overexpressed in a number of malignancies including breast
      cancer. In addition to Bmi-1, mammalian cells also express four other polycomb
      group (PcG) proteins that are closely related to Bmi-1. Virtually nothing is
      known about the role of these PcG proteins in oncogenesis. We have recently
      reported that Mel-18, a Bmi-1-related PcG protein, negatively regulates Bmi-1
      expression, and that its expression negatively correlates with Bmi-1 in
      proliferating and senescing human fibroblasts. Here, we report that the
      expression of Bmi-1 and Mel-18 inversely correlates in a number of breast cancer
      cell lines and in a significant number of breast tumor samples. Overexpression of
      Mel-18 results in repression of Bmi-1 and reduction of the transformed phenotype
      in malignant breast cancer cells. Furthermore, the repression of Bmi-1 by Mel-18
      is accompanied by the reduction of Akt/protein kinase B (PKB) activity in breast
      cancer cells. Similarly, Bmi-1 knockdown using RNA interference approach results
      in down-regulation of Akt/PKB activity and reduction in transformed phenotype of
      MCF7 cells. Importantly, we show that overexpression of constitutively active Akt
      overrides tumor-suppressive effect of Mel-18 overexpression and the knockdown of
      Bmi-1 expression. Thus, our studies suggest that Mel-18 and Bmi-1 may regulate
      the Akt pathway in breast cancer cells, and that Mel-18 functions as a tumor
      suppressor by repressing the expression of Bmi-1 and consequently down-regulating
      Akt activity.

PMID- 17545585
TI  - Reversible Smad-dependent signaling between tumor suppression and oncogenesis.
AB  - Cancer cells often gain advantage by reducing the tumor-suppressive activity of
      transforming growth factor-beta (TGF-beta) together with stimulation of its
      oncogenic activity as in Ras-transformed cells; however, molecular mechanisms
      remain largely unknown. TGF-beta activates both its type I receptor (TbetaRI) and
      c-Jun NH2-terminal kinase (JNK), which phosphorylate Smad2 and Smad3 at the COOH
      terminal (pSmad2/3C) and linker regions (pSmad2/3L). Here, we report that Ras
      transformation suppresses TbetaRI-mediated pSmad3C signaling, which involves
      growth inhibition by down-regulating c-Myc. Instead, hyperactive Ras
      constitutively stimulates JNK-mediated pSmad2/3L signaling, which fosters tumor
      invasion by up-regulating plasminogen activator inhibitor-1 and matrix
      metalloproteinase-1 (MMP-1), MMP-2, and MMP-9. Conversely, selective blockade of
      linker phosphorylation by a mutant Smad3 lacking JNK-dependent phosphorylation
      sites results in preserved tumor-suppressive function via pSmad3C in Ras
      transformed cells while eliminating pSmad2/3L-mediated invasive capacity. Thus,
      specific inhibition of the JNK/pSmad2/3L pathway should suppress cancer
      progression by shifting Smad-dependent signaling from oncogenesis to tumor
      suppression.

PMID- 17545586
TI  - DNA methylation and complete transcriptional silencing of cancer genes persist
      after depletion of EZH2.
AB  - Recent work suggests a link between the polycomb group protein EZH2 and mediation
      of gene silencing in association with maintenance of DNA methylation. However, we
      show that whereas basally expressed target cancer genes with minimal DNA
      methylation have increased transcription during EZH2 knockdown, densely DNA
      hypermethylated and silenced genes retain their methylation and remain
      transcriptionally silent. These results suggest that EZH2 can modulate
      transcription of basally expressed genes but not silent genes that are densely
      DNA methylated.

PMID- 17545587
TI  - Mainstream tobacco smoke causes paternal germ-line DNA mutation.
AB  - Despite the presence of known mutagens and carcinogens in cigarette smoke, there
      is currently no evidence to show that smoking, or exposure to cigarette smoke,
      can result in heritable genetic mutation. We show that male mice exposed to
      mainstream tobacco smoke (MTS) exhibit a significant increase in germ-line
      mutation frequency in spermatogonial stem cells. We exposed mature male mice to
      MTS for 6 or 12 weeks and investigated mutations arising in exposed
      spermatogonial stem cells at the expanded simple tandem repeat locus Ms6-hm. A
      generalized score test showed a significant treatment effect (P = 0.0214). Ms6-hm
      mutation frequency was 1.4 and 1.7 times higher in mice exposed to MTS for 6 and
      12 weeks, respectively, compared with sham controls. The data suggest that
      mutations accumulate in the spermatogonial stem cells with extended exposures.
      Mutation spectra were identical between exposed and sham individuals, supporting
      the hypothesis that tandem repeat mutations arise through indirect mechanisms of
      mutation. Mutations in sperm that are passed on to offspring cause permanent,
      irreversible changes in genetic composition and can persist in future
      generations. Our research suggests that the consequences of smoking extend beyond
      the smoker to their nonsmoking descendents.

PMID- 17545588
TI  - A role for the Fas/FasL system in modulating genetic susceptibility to T-cell
      lymphoblastic lymphomas.
AB  - The Fas/FasL system mediates induced apoptosis of immature thymocytes and
      peripheral T lymphocytes, but little is known about its implication in genetic
      susceptibility to T-cell malignancies. In this article, we report that the
      expression of FasL increases early in all mice after gamma-radiation treatments,
      maintaining such high levels for a long time in mice that resisted tumor
      induction. However, its expression is practically absent in T-cell lymphoblastic
      lymphomas. Interestingly, there exist significant differences in the level of
      expression between two mice strains exhibiting extremely distinct
      susceptibilities that can be attributed to promoter functional polymorphisms. In
      addition, several functional nucleotide changes in the coding sequences of both
      Fas and FasL genes significantly affect their biological activity. These results
      lead us to propose that germ-line functional polymorphisms affecting either the
      levels of expression or the biological activity of both Fas and FasL genes could
      be contributing to the genetic risk to develop T-cell lymphoblastic lymphomas and
      support the use of radiotherapy as an adequate procedure to choose in the
      treatment of T-cell malignancies.

PMID- 17545589
TI  - Molecular features of hormone-refractory prostate cancer cells by genome-wide
      gene expression profiles.
AB  - One of the most critical issues in prostate cancer clinic is emerging hormone
      refractory prostate cancers (HRPCs) and their management. Prostate cancer is
      usually androgen dependent and responds well to androgen ablation therapy.
      However, at a certain stage, they eventually acquire androgen-independent and
      more aggressive phenotype and show poor response to any anticancer therapies. To
      characterize the molecular features of clinical HRPCs, we analyzed gene
      expression profiles of 25 clinical HRPCs and 10 hormone-sensitive prostate
      cancers (HSPCs) by genome-wide cDNA microarrays combining with laser microbeam
      microdissection. An unsupervised hierarchical clustering analysis clearly
      distinguished expression patterns of HRPC cells from those of HSPC cells. In
      addition, primary and metastatic HRPCs from three patients were closely clustered
      regardless of metastatic organs. A supervised analysis and permutation test
      identified 36 up-regulated genes and 70 down-regulated genes in HRPCs compared
      with HSPCs (average fold difference > 1.5; P < 0.0001). We observed
      overexpression of AR, ANLN, and SNRPE and down-regulation of NR4A1, CYP27A1, and
      HLA-A antigen in HRPC progression. AR overexpression is likely to play a central
      role of hormone-refractory phenotype, and other genes we identified were
      considered to be related to more aggressive phenotype of clinical HRPCs, and in
      fact, knockdown of these overexpressing genes by small interfering RNA resulted
      in drastic attenuation of prostate cancer cell viability. Our microarray analysis
      of HRPC cells should provide useful information to understand the molecular
      mechanism of HRPC progression and to identify molecular targets for development
      of HRPC treatment.

PMID- 17545590
TI  - Insertional mutagenesis reveals progression genes and checkpoints in MYC/Runx2
      lymphomas.
AB  - In this study, we have exploited the power of insertional mutagenesis to
      elucidate tumor progression pathways in mice carrying two oncogenes (MYC/Runx2)
      that collaborate to drive early lymphoma development. Neonatal infection of these
      mice with Moloney murine leukemia virus resulted in accelerated tumor onset with
      associated increases in clonal complexity and lymphoid dissemination. Large-scale
      analysis of retroviral integration sites in these tumors revealed a profound bias
      towards a narrow range of target genes, including Jdp2 (Jundm2), D cyclin, and
      Pim family genes. Remarkably, direct PCR analysis of integration hotspots
      revealed that every progressing tumor consisted of multiple clones harboring hits
      at these loci, giving access to large numbers of independent insertion events and
      uncovering the contrasting mutagenic mechanisms operating at each target gene.
      Direct PCR analysis showed that high-frequency targeting occurs only in the tumor
      environment in vivo and is specific for the progression gene set. These results
      indicate that early lymphomas in MYC/Runx2 mice remain dependent on exogenous
      growth signals, and that progression can be achieved by constitutive activation
      of pathways converging on a cell cycle checkpoint that acts as the major rate
      limiting step for lymphoma outgrowth.

PMID- 17545591
TI  - X inactive-specific transcript RNA coating and genetic instability of the X
      chromosome in BRCA1 breast tumors.
AB  - Identification among breast tumors of those arising in a hereditary BRCA1 context
      remains a medical challenge. Abnormalities in X chromosome copy number and in the
      epigenetic stability of the inactive X chromosome (Xi) have been proposed to
      characterize BRCA1 breast tumors. In particular, it has been proposed that loss
      of BRCA1 function can lead to loss of X inactive-specific transcript (XIST) RNA
      association with the Xi. However, few studies have addressed this issue in a
      sufficiently large series of BRCA1 primary tumors. Here we assess X-chromosome
      status using single-cell (RNA and DNA fluorescence in situ hybridization) and
      global genomic (array-comparative genomic hybridization and allelotyping)
      approaches on a series of 11 well-defined BRCA1 tumors. We show that many or most
      cells of the tumors contain one or more XIST RNA domains. Furthermore, the number
      of XIST RNA domains per cell varied considerably even within a single tumor.
      Frequent X-chromosome allelic and copy number aberrations were found, in
      agreement with aberrant XIST RNA domain numbers. In summary, by combining
      multiple approaches to assess the genetics and epigenetics of a large series of
      BRCA1 primary tumors, we can conclude definitively that BRCA1 is not required for
      XIST RNA coating of the X chromosome. The intratumoral and intertumoral
      variability in XIST RNA domain number in BRCA1 tumors correlates with chromosomal
      genetic abnormalities, including gains, losses, reduplications, and
      rearrangements of the X-chromosome. Finally, we also show the necessity for
      combined global and single-cell approaches in the assessment of tumors with such
      a high degree of heterogeneity.

PMID- 17545592
TI  - Human macrophages promote the motility and invasiveness of osteopontin-knockdown
      tumor cells.
AB  - Increasing evidence indicates that macrophages in tumor stroma can significantly
      modify the malignant phenotypes of tumors. Osteopontin (OPN) is frequently
      overexpressed in cancers with high metastatic capacity and, thus, has been
      considered as a potential therapeutic target. To find out whether macrophages can
      affect the outcome of OPN-knockdown tumor cells, we used RNA interference (RNAi)
      to stably silence the OPN expression in the highly invasive human hepatoma cell
      line SK-Hep-1. Silencing of OPN markedly decreased the motility and invasiveness
      of the SK-Hep-1 cells. Further studies using this cell model revealed that
      coculture with human macrophages or macrophage-conditioned medium largely
      restored the migration and invasion potential of OPN-knockdown tumor cells.
      Moreover, such macrophage-promoted motility can be effectively blocked either by
      the addition of OPN-neutralizing antibody to the cocultured medium or by
      silencing OPN expression in macrophages. These results indicate that macrophage
      derived OPN can compensate for the decrease of OPN and thereby restore the
      metastatic potential of OPN-knockdown tumor cells. Further characterization of
      the underlying mechanisms disclosed that macrophage-derived OPN exerted its
      function independently of the actin cytoskeleton rearrangement or the activation
      of matrix metalloproteinase and Rho families. Our results suggest that there are
      fine-tuned complex interactions between cancer cells and stroma cells, which may
      modify the outcome of cancer therapy, and therefore should be considered for the
      rational design of anticancer strategy.

PMID- 17545593
TI  - Retroviral insertional mutagenesis identifies genes that collaborate with NUP98
      HOXD13 during leukemic transformation.
AB  - The t(2;11)(q31;p15) chromosomal translocation results in a fusion between the
      NUP98 and HOXD13 genes and has been observed in patients with myelodysplastic
      syndrome (MDS) or acute myelogenous leukemia. We previously showed that
      expression of the NUP98-HOXD13 (NHD13) fusion gene in transgenic mice results in
      an invariably fatal MDS; approximately one third of mice die due to complications
      of severe pancytopenia, and about two thirds progress to a fatal acute leukemia.
      In the present study, we used retroviral insertional mutagenesis to identify
      genes that might collaborate with NHD13 as the MDS transformed to an acute
      leukemia. Newborn NHD13 transgenic mice and littermate controls were infected
      with the MOL4070LTR retrovirus. The onset of leukemia was accelerated, suggesting
      a synergistic effect between the NHD13 transgene and the genes neighboring
      retroviral insertion events. We identified numerous common insertion sites
      located near protein-coding genes and confirmed dysregulation of a subset of
      these by expression analyses. Among these genes were Meis1, a known collaborator
      of HOX and NUP98-HOX fusion genes, and Mn1, a transcriptional coactivator
      involved in human leukemia through fusion with the TEL gene. Other putative
      collaborators included Gata2, Erg, and Epor. Of note, we identified a common
      insertion site that was >100 kb from the nearest coding gene, but within 20 kb of
      the miR29a/miR29b1 microRNA locus. Both of these miRNA were up-regulated,
      demonstrating that retroviral insertional mutagenesis can target miRNA loci as
      well as protein-coding loci. Our data provide new insights into NHD13-mediated
      leukemogenesis as well as retroviral insertional mutagenesis mechanisms.

PMID- 17545594
TI  - The peroxisome proliferator WY-14,643 promotes hepatocarcinogenesis caused by
      endogenously generated oxidative DNA base modifications in repair-deficient
      Csbm/m/Ogg1-/- mice.
AB  - Basal levels of endogenously generated oxidative DNA modifications such as 7,8
      dihydro-8-oxoguanine (8-oxoG) are present in apparently all mammalian cells, but
      their relevance for the generation of spontaneous cancers remains to be
      established. Both the 8-oxoG levels and the resulting spontaneous mutations are
      increased in the livers of Csb(m/m)/Ogg1(-/-) mice, which are deficient in the
      repair of 8-oxoG. In order to determine the consequences of these additional
      oxidative DNA modifications and mutations and thus assess the tumor initiating
      potency of this type of endogenous DNA damage, we treated Csb(m/m)/Ogg1(-/-) mice
      and repair-proficient controls with the peroxisome proliferator WY-14,643 (0.025%
      ad libitum), a potent inducer of liver cell proliferation. The treatment did not
      generate any additional oxidative DNA damage; the elevated levels of 8-oxoG in
      the Csb(m/m)/Ogg1(-/-) mice even decreased. Also, the spontaneous mutation
      frequencies observed in the lacI gene of BigBlue Csb(m/m)/Ogg1(-/-) mice, which
      were approximately 3-fold higher than in the repair-proficient mice, declined by
      39% under the treatment, whereas the frequencies in the livers of the repair
      proficient animals remained unchanged. Preneoplastic lesions (staining positive
      or negative for glucose-6-phoshatase) developed in the livers of both wild-type
      and Csb(m/m)/Ogg1(-/-) mice after 30 weeks. Both the numbers and the total
      volumes of the lesions were approximately 6-fold higher in the repair-deficient
      mice than in the wild-type mice. The results indicate that spontaneous mutations
      generated from endogenous oxidative DNA base damage efficiently translate into
      increased tumorigenesis when cell proliferation is stimulated.

PMID- 17545595
TI  - Inhibition of tumor growth and metastasis by depletion of vesicular sorting
      protein Hrs: its regulatory role on E-cadherin and beta-catenin.
AB  - Abnormally high signals from receptor tyrosine kinases (RTK) are associated with
      carcinogenesis, and impaired deactivation of RTKs may also be a mechanism in
      cancer. Hepatocyte growth factor-regulated tyrosine kinase substrate (Hrs) is one
      of the master regulators that sort activated receptors toward lysosomes and shut
      down their signals. Hrs contains a ubiquitin-interacting motif and is involved in
      the endosomal sorting of monoubiquitinated membrane proteins, such as growth
      factor receptor and E-cadherin. Here, we investigated the role of Hrs in
      determining the malignancy of cancer cells and discovered that the targeted
      disruption of Hrs by small interfering RNA effectively attenuated the
      proliferation, anchorage-independent growth, tumorigenesis, and metastatic
      potential of HeLa cells in vitro and in vivo. The restoration of Hrs expression
      increased cell proliferation and anchorage-independent growth in a mouse
      embryonic fibroblast line established from a Hrs knockout mouse. Further analysis
      revealed that Hrs depletion was associated with the up-regulation of E-cadherin
      and reduced beta-catenin signaling. The aberrant accumulation of E-cadherin most
      likely resulted from impaired E-cadherin degradation in lysosomes. These results
      suggest that Hrs may play a critical role in determining the malignancy of cancer
      cells by regulating the degradation of E-cadherin.

PMID- 17545596
TI  - Melanocyte expression of survivin promotes development and metastasis of UV
      induced melanoma in HGF-transgenic mice.
AB  - We previously found the apoptosis inhibitor Survivin to be expressed in
      melanocytic nevi and melanoma but not in normal melanocytes. To investigate the
      role of Survivin in melanoma development and progression, we examined the
      consequences of forced Survivin expression in melanocytes in vivo. Transgenic
      (Tg) mouse lines (Dct-Survivin) were generated with melanocyte-specific
      expression of Survivin, and melanocytes grown from Dct-Survivin mice expressed
      Survivin. Dct-Survivin melanocytes exhibited decreased susceptibility to UV
      induced apoptosis but no difference in proliferative capacity compared with
      melanocytes derived from non-Tg littermates. Induction of nevi in Dct-Survivin
      and non-Tg mice by topical application of 7,12-dimethylbenz(a)anthracene did not
      reveal significant differences in lesion onset (median, 10 weeks) or density (4
      lesions per mouse after 15 weeks). Dct-Survivin mice were bred with melanoma
      prone MH19/HGF-B6 Tg mice, and all progeny expressing either individual, neither,
      or both (Survivin/HGF) transgenes were UV-treated as neonates and then monitored
      for 43 weeks. Melanocytes in neonatal Survivin+/HGF+ mouse skin were less
      susceptible to UV-induced apoptosis than those from Survivin-/HGF+ mice. Onset of
      melanocytic tumors was earlier (median, 18 versus 24 weeks; P = 0.01, log-rank
      test), and overall tumor density was greater (7.7 versus 5.2 tumors per mouse; P
      = 0.04) in Survivin+/HGF+ compared with Survivin-/HGF+ mice. Strikingly,
      melanomas arising in Survivin+/HGF+ mice showed a greater tendency for lymph node
      (35% versus 0%; P = 0.04) and lung (53% versus 22%) metastasis and lower rates of
      spontaneous apoptosis than those in Survivin-/HGF+ mice. These studies show a
      role for Survivin in promoting both early and late events of UV-induced melanoma
      development in vivo.

PMID- 17545597
TI  - Apoptosis suppression by somatic cell transfer of Bcl-2 promotes Sonic hedgehog
      dependent medulloblastoma formation in mice.
AB  - Medulloblastomas are malignant brain tumors that arise in the cerebellum in
      children. Aberrant activation of the Sonic hedgehog (Shh) signaling pathway,
      which normally stimulates proliferation of granule neuron precursors (GNP) during
      cerebellar development, induces tumors in mice that closely mimic human
      medulloblastomas. Shh-dependent medulloblastoma formation is enhanced by
      hyperactive insulin-like growth factor (IGF) signaling and ectopic expression of
      Myc oncogenes. This enhanced tumorigenesis stems from the sensitivity of GNPs to
      IGF and Myc levels in regulating proliferation. An emerging theme in cancer
      research is that oncogene-induced cell proliferation cannot initiate neoplastic
      transformation unless cellular programs that mediate apoptosis are disabled.
      Here, we report a high frequency of medulloblastoma formation in mice after
      postnatal overexpression of the antiapoptotic protein Bcl-2 in cooperation with
      Shh. Ectopic expression of Bcl-2 alone or in combination with N-Myc did not
      induce tumors, indicating that Shh has essential transforming functions in GNPs
      not supplied by the mitogenic stimulus of N-Myc combined with a strong
      antiapoptotic signal provided by Bcl-2. Expression of endogenous Bcl-2 was not up
      regulated in Shh-induced tumors. Instead, elevated levels of phosphorylated Akt
      were found, suggesting that activated phosphatidylinositol 3-kinase signaling is
      one intrinsic mechanism for suppressing apoptosis in Shh-dependent
      medulloblastomas. Thus, blockade of apoptosis cooperates with Shh-stimulated
      proliferation to transform GNPs and induce aggressive medulloblastomas. These
      findings provide insights into the molecular signals that initiate
      medulloblastoma formation and they support the importance of blocking apoptosis
      in carcinogenesis.

PMID- 17545598
TI  - T-lymphokine-activated killer cell-originated protein kinase functions as a
      positive regulator of c-Jun-NH2-kinase 1 signaling and H-Ras-induced cell
      transformation.
AB  - T-lymphokine-activated killer cell-originated protein kinase (TOPK) is
      overexpressed in highly proliferating tumors such as leukemias and myelomas, and
      seems to play a key role in tumorigenesis or metastasis. However, the precise
      role and regulatory mechanism explaining the effects of TOPK on tumor cells still
      remain elusive. Here, we reported that TOPK regulates UVB-induced c-Jun-NH2
      kinase 1 (JNK1) activity, and is essential for H-Ras-induced activator protein-1
      activity and cell transformation. We showed that TOPK associated with and
      phosphorylated JNK1 following UVB irradiation in vitro or in vivo. Moreover, UVB
      induced JNK1 activity was greatly augmented in mouse epidermal JB6 Cl41 cells
      that stably expressed TOPK cDNA. On the other hand, JNK1 activity was markedly
      attenuated by stable expression of small interfering RNA against TOPK in
      malignant melanoma RPMI 7951 cells. Interestingly, TOPK interacted with JNK
      interacting protein 1 and caused an elevation of JNK-interacting protein 1
      scaffolding activity, thereby enhancing JNK1 activity. Furthermore, JNK1 was
      required for TOPK-mediated activator protein-1 transcriptional activity and
      transformed foci induced by UVB or H-Ras. Taken together, these findings showed
      that TOPK positively modulated UVB-induced JNK1 activity and played a pivotal
      role in JNK1-mediated cell transformation induced by H-Ras. These studies might
      also provide a novel molecular mechanism for the role of TOPK in UVB-mediated
      skin carcinogenesis.

PMID- 17545599
TI  - Whole-body subcellular multicolor imaging of tumor-host interaction and drug
      response in real time.
AB  - To noninvasively image cancer cell/stromal cell interaction in the tumor
      microenvironment and drug response at the cellular level in live animals in real
      time, we developed a new imageable three-color animal model. The model consists
      of green fluorescent protein (GFP)-expressing mice transplanted with dual-color
      cancer cells labeled with GFP in the nucleus and red fluorescent protein in the
      cytoplasm. The Olympus IV100 Laser Scanning Microscope, with ultra-narrow
      microscope objectives ("stick objectives"), is used for three-color whole-body
      imaging of the two-color cancer cells interacting with the GFP-expressing stromal
      cells. In this model, drug response of both cancer and stromal cells in the
      intact live animal is also imaged in real time. Various in vivo phenomena of
      tumor-host interaction and cellular dynamics were imaged, including mitotic and
      apoptotic tumor cells, stromal cells interacting with the tumor cells, tumor
      vasculature, and tumor blood flow. This new model system enables the first
      cellular and subcellular images of unperturbed tumors in the live intact animal.
      New visible real-time targets for novel anticancer agents are provided in this
      model, including the color-coded interacting cancer and stromal cells, tumor
      vasculature, and blood flow. This imageable model should lead to many new
      insights of in vivo cancer cell biology and to novel drug discovery.

PMID- 17545600
TI  - Platelet-derived growth factor receptor beta-mediated phosphorylation of MUC1
      enhances invasiveness in pancreatic adenocarcinoma cells.
AB  - MUC1 is a heterodimeric transmembrane glycoprotein that is overexpressed and
      aberrantly glycosylated in ductal adenocarcinomas. Differential phosphorylation
      of the MUC1 cytoplasmic tail (MUC1CT) has been associated with signaling events
      that influence the proliferation and metastasis of cancer cells. We identified a
      novel tyrosine phosphorylation site (HGRYVPP) in the MUC1CT by mass spectrometric
      analysis of MUC1 from human pancreatic adenocarcinoma cell lines. Analyses in
      vitro and in vivo showed that platelet-derived growth factor receptor beta
      (PDGFRbeta) catalyzed phosphorylation of this site and of tyrosine in the RDTYHPM
      site. Stimulation of S2-013.MUC1F cells with PDGF-BB increased nuclear
      colocalization of MUC1CT and beta-catenin. PDGF-BB stimulation had no significant
      effect on cell proliferation rate; however, it enhanced invasion in vitro through
      Matrigel and in vivo tumor growth and metastases. Invasive properties of the
      cells were significantly altered on expression of phosphorylation-abrogating or
      phosphorylation-mimicking mutations at these sites. We propose that interactions
      of MUC1 and PDGFRbeta induce signal transduction events that influence the
      metastatic properties of pancreatic adenocarcinoma.

PMID- 17545601
TI  - Distinctive features of angiogenesis and lymphangiogenesis determine their
      functionality during de novo tumor development.
AB  - Blood and lymphatic vasculature are essential components of all organs,
      responsible for maintaining organ fluid dynamics and tissue homeostasis. Although
      both vessel systems are composed of similar lineages of endothelial cells whose
      crude functions include fluid and cell transport, each system also possesses
      distinctive physiologic properties, enabling their distinctive functions in
      tissues. The role of hematogenous vasculature and development of angiogenic blood
      vessels during cancer development is well established; however, the role of
      lymphangiogenesis and structural/functional alterations occurring within
      lymphatic vessels during cancer development are incompletely understood. To
      assess premalignant versus malignant alterations in blood and lymphatic
      vasculature associated with squamous epithelial skin carcinogenesis, we assessed
      architectural and functional features of both vascular systems using a mouse
      model of de novo carcinoma development. We report that, as vasculature acquires
      angiogenic and/or lymphangiogenic properties, angiogenic blood vessels become
      leaky in premalignant tissue and at peripheries of carcinomas, where enlarged
      lymphatic capillaries efficiently drain increased tissue fluid, thereby
      maintaining tissue hemodynamics. In contrast, central regions of carcinomas
      exhibit elevated tissue fluid levels, compressed lymphatic lumina, and decreased
      vascular leakage, thus indicating impaired hemodynamics within solid tumors.
      Together, these data support the notion that therapeutic delivery of anticancer
      agents is best realized in premalignant tissues and/or at the peripheries of
      solid tumors where hemodynamic forces support drug delivery. Strategies to
      normalize intratumoral hemodynamics would therefore enhance therapeutic delivery
      to otherwise poorly accessible central regions of solid tumors.

PMID- 17545602
TI  - Kallikrein 4 is a proliferative factor that is overexpressed in prostate cancer.
AB  - Kallikrein 4 (KLK4) is a member of the human tissue KLK family. Whereas all other
      KLKs are secreted proteins with extracellular functions, KLK4 is primarily
      localized to the nucleus, indicating that it has a different function compared
      with other members of the KLK family. In addition, KLK4 expression is highly
      enriched in the prostate and is regulated by androgens. Here, we studied the
      possible functional role of KLK4 in prostate cancer cells and examined its
      expression at the protein level in prostate cancer specimens. Consistent with its
      mRNA expression, KLK4 protein is significantly overexpressed in malignant
      prostate compared with normal prostate. KLK4 expression is predominantly in the
      nucleus of basal cells in the prostate epithelium in keeping with its
      distribution in prostate cancer cells in vitro. Furthermore, adenovirus-mediated
      expression of KLK4 dramatically induces proliferation of prostate cancer cells,
      at least in part through significant alterations in cell cycle regulatory gene
      expression. Consistent with these data, small interfering RNA-mediated knockdown
      of endogenous KLK4 in LNCaP prostate cancer cells inhibits cell growth. These
      data identify KLK4 as the first member of the KLK family that is a proliferative
      factor with effects on gene expression and indicate that it may have an important
      role in prostate cancer development and progression.

PMID- 17545603
TI  - Arsenic induced mitochondrial DNA damage and altered mitochondrial oxidative
      function: implications for genotoxic mechanisms in mammalian cells.
AB  - Arsenic is a well-established human carcinogen that is chronically consumed in
      drinking water by millions of people worldwide. Recent evidence has suggested
      that arsenic is a genotoxic carcinogen. Furthermore, we have shown that
      mitochondria mediate the mutagenic effects of arsenic in mammalian cells, as
      arsenic did not induce nuclear mutations in mitochondrial DNA (mtDNA)-depleted
      cells. Using the human-hamster hybrid A(L) cells, we show here that arsenic
      alters mitochondrial function by decreasing cytochrome c oxidase function and
      oxygen consumption but increasing citrate synthase function. These alterations
      correlated with depletion in mtDNA copy number and increase in large
      heteroplasmic mtDNA deletions. In addition, mtDNA isolated periodically from
      cultures treated continuously with arsenic did not consistently display the same
      deletion pattern, indicating that the mitochondrial genome was subjected to
      repeated and continuous damage. These data support the theory that the
      mitochondria, and particularly mtDNA, are important targets of the mutagenic
      effects of arsenic in mammalian cells.

PMID- 17545604
TI  - Chemoresistant KM12C colon cancer cells are addicted to low cyclic AMP levels in
      a phosphodiesterase 4-regulated compartment via effects on phosphoinositide 3
      kinase.
AB  - One of the major problems in treating colon cancer is chemoresistance to
      cytotoxic chemotherapeutic agents. There is therefore a need to devise new
      strategies to inhibit colon cancer cell growth and survival. Here, we show that a
      combination of low doses of the adenylyl cyclase activator forskolin together
      with the specific cyclic AMP (cAMP) phosphodiesterase-4 (PDE4) inhibitor
      rolipram, but not the cAMP phosphodiesterase-3 (PDE3) inhibitor cilostamide,
      causes profound growth arrest of chemoresistant KM12C colon cancer cells. Low
      dose forskolin causes KM12C cells to exit the cell cycle in G1 by inducing
      p27(Kip1) and primes cells for apoptosis on addition of rolipram. The effect of
      the low-dose forskolin/rolipram combination is mediated by displacement of the
      phosphatidylinositol 3,4,5-trisphosphate/phosphoinositide 3-kinase signaling
      module from the plasma membrane and suppression of the Akt/protein kinase-B
      oncogene pathway, to which KM12C cells are addicted for growth. The cAMP and
      phosphoinositide 3-kinase pathways form a critical intersection in this response,
      and reexpression of the tumor suppressor lipid phosphatase, phosphatase and
      tensin homologue, which is commonly lost or mutated in colon cancer, sensitizes
      KM12C cells to growth inhibition by challenge with low-dose forskolin. Certain
      chemoresistant colon cancer cells are therefore exquisitely sensitive to subtle
      elevation of cAMP by a synergistic low-dose adenylyl cyclase activator/PDE4
      inhibitor combination. Indeed, these cells are addicted to maintenance of low
      cAMP concentrations in a compartment that is regulated by PDE4. Well-tolerated
      doses of PDE4 inhibitors that are already in clinical development for other
      therapeutic indications may provide an exciting new strategy for the treatment of
      colon cancer.

PMID- 17545605
TI  - ACTIBIND, a T2 RNase, competes with angiogenin and inhibits human melanoma
      growth, angiogenesis, and metastasis.
AB  - Melanoma is a very aggressive and highly angiogenic tumor in which standard
      treatments have had only limited success. Patients with advanced disease have a 5
      year survival rate of 5%. In search for alternatives, we identified a natural
      product extracted from the fungus Aspergillus niger, termed ACTIBIND, that
      inhibits tumor growth and metastasis of melanoma in vivo. ACTIBIND, a T2 RNase,
      exerts antitumorigenic and antiangiogenic activities by competing with the
      angiogenic factor angiogenin (itself an RNase homologue). Thus, there was
      decreased expression and activity of the matrix metalloproteinase 2 in melanoma
      and vascular endothelial cells, decreased vascularization, and increased tumor
      cell apoptosis in vivo. ACTIBIND significantly inhibited angiogenesis in an in
      vivo angiogenesis assay with sponges containing angiogenin. In vitro, ACTIBIND
      was internalized by both melanoma and human umbilical vein endothelial cells,
      reached the cell nuclei, and inhibited the activity of angiogenin response
      elements in a dose-dependent manner. Collectively, our data indicate that
      ACTIBIND should be tested for its potential as a new antiangiogenic modality for
      the treatment of melanoma.

PMID- 17545606
TI  - Somatic mutations in the tyrosine kinase domain of epidermal growth factor
      receptor (EGFR) abrogate EGFR-mediated radioprotection in non-small cell lung
      carcinoma.
AB  - The epidermal growth factor receptor (EGFR) is an important determinant of
      radioresponse, whose elevated expression and activity frequently correlates with
      radioresistance in several cancers, including non-small cell lung carcinoma
      (NSCLC). We reported recently that NSCLC cell lines harboring somatic, activating
      mutations in the tyrosine kinase domain (TKD) of the EGFR exhibit significant
      delays in the repair of DNA double-strand breaks (DSB) and poor clonogenic
      survival in response to radiation. Here, we explore the mechanisms underlying
      mutant EGFR-associated radiosensitivity. In three representative NSCLC cell
      lines, we show that, unlike wild-type (WT) EGFR, receptors with common oncogenic
      TKD mutations, L858R or DeltaE746-E750, are defective in radiation-induced
      translocation to the nucleus and fail to bind the catalytic and regulatory
      subunits of the DNA-dependent protein kinase (DNA-PK), a key enzyme in the
      nonhomologous end-joining repair pathway. Moreover, despite the presence of WT
      EGFR, stable exogenous expression of either the L858R or the DeltaE746-E750
      mutant forms of EGFR in human bronchial epithelial cells significantly delays
      repair of ionizing radiation (IR)-induced DSBs, blocks the resolution of frank or
      microhomologous DNA ends, and abrogates IR-induced nuclear EGFR translocation or
      binding to DNA-PK catalytic subunit. Our study has identified a subset of
      naturally occurring EGFR mutations that lack a critical radioprotective function
      of EGFR, providing valuable insights on how the EGFR mediates cell survival in
      response to radiation in NSCLC cell lines.

PMID- 17545607
TI  - HS1-associated protein X-1 regulates carcinoma cell migration and invasion via
      clathrin-mediated endocytosis of integrin alphavbeta6.
AB  - Enhanced expression levels of integrin alphavbeta6 have been linked to more
      aggressive invasive carcinoma cell behavior and poorer clinical prognosis.
      However, how alphavbeta6 determines invasion and the dynamics of integrin
      alphavbeta6 regulation in tumor cells are poorly understood. We have identified
      the 35-kDa HS1-associated protein X-1 (HAX-1) protein as a novel binding partner
      of the beta6 cytoplasmic tail using a yeast two-hybrid screen. We show that
      alphavbeta6-dependent migration is blocked following small interfering RNA
      (siRNA)-mediated depletion of HAX-1 in oral squamous cell carcinoma cell lines.
      Using both siRNA and membrane-permeable peptides, we show that alphavbeta6
      dependent migration and invasion require HAX-1 to bind directly to beta6 and
      thereby regulate clathrin-mediated endocytosis of alphavbeta6 integrins.
      Progression of oral cancer is associated with enhanced expression of alphavbeta6
      and HAX-1 proteins in patient tissue. This report establishes that integrin
      endocytosis is required for alphavbeta6-dependent carcinoma cell motility and
      invasion and suggests that this process is an important mechanism in cancer
      progression.

PMID- 17545608
TI  - Extracellular signal-regulated kinase is a target of cyclooxygenase-1-peroxisome
      proliferator-activated receptor-delta signaling in epithelial ovarian cancer.
AB  - The underlying causes of epithelial ovarian cancer (EOC) are unclear, and
      treatment options for patients with advanced disease are limited. There is
      evidence that the use of nonsteroidal anti-inflammatory drugs is associated with
      decreased risk of developing EOC. Nonsteroidal anti-inflammatory drugs inhibit
      cyclooxygenase (COX)-1 and COX-2, which catalyze prostaglandin biosynthesis. We
      previously showed that mouse and human EOCs have increased levels of COX-1, but
      not COX-2, and a COX-1-selective inhibitor, SC-560, attenuates prostaglandin
      production and tumor growth. However, the downstream targets of COX-1 signaling
      in EOC are not yet known. To address this question, we evaluated peroxisome
      proliferator-activated receptor delta (PPARdelta) expression and function in EOC.
      We found that EOC cells express high levels of PPARdelta, and neutralizing
      PPARdelta function reduces tumor growth in vivo. More interestingly, aspirin, a
      nonsteroidal anti-inflammatory drug that preferentially inhibits COX-1,
      compromises PPARdelta function and cell growth by inhibiting extracellular signal
      regulated kinases 1/2, members of the mitogen-activated protein kinase family.
      Our study, for the first time, shows that whereas PPARdelta can be a target of
      COX-1, extracellular signal-regulated kinase is a potential target of PPARdelta.
      The ability of aspirin to inhibit EOC growth in vivo is an exciting finding
      because of its low cost, lack of cardiovascular side effects, and availability.

PMID- 17545609
TI  - Metastatic potential of 21T human breast cancer cells depends on Akt/protein
      kinase B activation.
AB  - Most cancer lethality is caused by metastasis. To gain insight into the molecular
      basis of tumor progression to metastasis, we used the 21T series of human mammary
      epithelial cells obtained by successive biopsies from one breast cancer patient.
      The c-erbB2 gene is amplified and overexpressed in each of three 21T tumor lines.
      The erbB receptor tyrosine kinase-activated phosphatidylinositol 3-kinase/Akt
      signaling cascade is crucial for the development and maintenance of epithelial
      cells, and dysregulation of this pathway is frequently associated with cellular
      transformation and cancer. For Akt to be fully activated, Ser(473) on its COOH
      terminus needs to be phosphorylated. We detected more Ser(473) Akt
      phosphorylation in MT cells, derived from a pleural effusion, compared with cells
      from the primary tumor. This phosphorylation has recently been shown to be
      catalyzed by mammalian target of rapamycin (mTOR)/rictor kinase. By using genetic
      and pharmacologic activators and inhibitors, we showed that Ser(473) Akt
      phosphorylation is more sensitive to mTOR/rictor inhibition in metastatic tumor
      cells than normal mammary epithelial and primary tumor cells. The mTOR/rictor
      kinase activity was indispensable for both Ser(473) Akt phosphorylation and
      migration of metastatic MT2 cells. In addition, a large decrease of protein
      phosphatase PH domain leucine-rich repeat protein phosphatase (PHLPP) was found,
      which could be responsible for the overexpression of Ser(473) Akt in MT cells.
      Our data indicate that these breast cancer cells acquire new vulnerabilities,
      rictor and PHLPP, which might provide an Achilles' heel for therapeutic
      intervention of breast cancer metastasis.

PMID- 17545610
TI  - Alternative BCR/ABL splice variants in Philadelphia chromosome-positive leukemias
      result in novel tumor-specific fusion proteins that may represent potential
      targets for immunotherapy approaches.
AB  - Imatinib currently represents the standard treatment in the early chronic phase
      of chronic myelogenous leukemia (CML), thanks to the high percentage of
      cytogenetic complete remission achieved, but it is yet unclear to what extent it
      can eradicate leukemia. Therefore, different vaccination strategies have been
      suggested, mainly based on the exploitment of the junctional peptides spanning
      the fusion region of the Bcr/Abl proteins. To identify new potential immunologic
      targets, 63 Philadelphia chromosome-positive patients and 6 BCR/ABL-positive cell
      lines were tested in nested reverse transcriptase PCR to detect the presence of
      BCR/ABL transcripts arising from the alternative splicing of the main BCR/ABL
      transcripts. We could detect BCR/ABL transcripts with junctions between BCR exon
      1, 13, or 14 and ABL exon 4 in approximately 80% of patients and 84% of cell
      lines, beside the main fusion transcripts. Translation products of these
      transcripts were characterized at their COOH terminus by a large amino acid
      portion derived from the out of frame (OOF) reading of ABL gene. These proteins
      were detected in BCR/ABL-positive cell lines by immunoprecipitation and
      immunohistochemistry. Finally, we determined whether OOF-specific CD8+ T cells
      could be found in the peripheral blood of CML patients and whether they could
      acquire effector function following in vitro sensitization with OOF-derived
      peptides predicted to bind to human leucocyte antigen (HLA)-A2 and HLA-A3
      molecules. We detected the presence of OOF-specific CD8+ T cells in four of four
      patients studied, and in one case, these T cells exhibited specific cytotoxic
      activity against both peptide-pulsed targets and autologous primary CML cells.

PMID- 17545611
TI  - Protein kinase Calpha determines HER2 fate in breast carcinoma cells with HER2
      protein overexpression without gene amplification.
AB  - In some HER2-positive breast tumors, cell surface overexpression of HER2 is not
      associated with gene amplification but may instead rest in altered gene
      transcription, half-life, or recycling of the oncoprotein. Here, we show that
      HER2 overexpression in HER2 2+ carcinomas is associated with neither an increase
      in gene transcription nor a deregulation in the ubiquitin-dependent pathways, but
      instead seems to be regulated by protein kinase Calpha (PKCalpha) activity. The
      stimulation of PKCalpha up-regulated HER2 expression, whereas PKCalpha inhibition
      by pharmacologic treatments and PKCalpha-specific small interfering RNA led to a
      dramatic down-regulation of HER2 levels only in breast cancer cells HER2 2+.
      Consistent with the in vitro data, our biochemical analysis of HER2 2+ human
      primary breast specimens revealed significantly higher levels of phosphorylated
      PKCalpha compared with HER2-negative tumors. Inhibition of HER2 activation by the
      tyrosine kinase inhibitor lapatinib led to decreased levels of PKCalpha
      phosphorylation, clearly indicating a cross-talk between PKCalpha and HER2
      molecules. These data suggest that HER2 overexpression in HER2 2+ carcinomas is
      due to an accumulation of the recycled oncoprotein to the cell surface induced by
      activated PKCalpha.

PMID- 17545612
TI  - Histone deacetylase inhibitors sensitize prostate cancer cells to agents that
      produce DNA double-strand breaks by targeting Ku70 acetylation.
AB  - This study reports a histone deacetylation-independent mechanism whereby histone
      deacetylase (HDAC) inhibitors sensitize prostate cancer cells to DNA-damaging
      agents by targeting Ku70 acetylation. Ku70 represents a crucial component of the
      nonhomologous end joining repair machinery for DNA double-strand breaks (DSB).
      Our data indicate that pretreatment of prostate cancer cells with HDAC inhibitors
      (trichostatin A, suberoylanilide hydroxamic acid, MS-275, and OSU-HDAC42) led to
      increased Ku70 acetylation accompanied by reduced DNA-binding affinity without
      disrupting the Ku70/Ku80 heterodimer formation. As evidenced by increased
      Ser(139)-phosphorylated histone H2AX (gammaH2AX), impaired Ku70 function
      diminished cellular capability to repair DNA DSBs induced by bleomycin,
      doxorubicin, and etoposide, thereby enhancing their cell-killing effect. This
      sensitizing effect was most prominent when cells were treated with HDAC
      inhibitors and DNA-damaging agents sequentially. Mimicking acetylation was done
      by replacing K282, K317, K331, K338, K539, or K542 with glutamine via site
      directed mutagenesis, which combined with computer docking analysis was used to
      analyze the role of these lysine residues in the interactions of Ku70 with DNA
      broken ends. Mutagenesis of K282, K338, K539, or K542 suppressed the activity of
      Ku70 to bind DNA, whereas mutagenesis of K317 or K331 with glutamine had no
      significant effect. Moreover, overexpression of K282Q or K338Q rendered DU-145
      cells more susceptible to the effect of DNA-damaging agents on gammaH2AX
      formation and cell killing. Overall, the ability of HDAC inhibitors to regulate
      cellular ability to repair DNA damage by targeting Ku70 acetylation underlies the
      viability of their combination with DNA-damaging agents as a therapeutic strategy
      for prostate cancer.

PMID- 17545613
TI  - Down-regulation of PU.1 by methylation of distal regulatory elements and the
      promoter is required for myeloma cell growth.
AB  - The transcription factor PU.1 is essential for myeloid and B-cell development.
      Down-regulation of PU.1 by disruption of its 14-kb 5' upstream regulatory element
      induced acute myeloid leukemia, T-cell lymphoma, and chronic lymphocytic leukemia
      like disease in murine models. In the present study, we found that PU.1 was down
      regulated in the majority of human myeloma cell lines and a subset of freshly
      isolated myeloma cells, in contrast to relatively high expression of PU.1 in
      normal plasma cells. Patients in this low PU.1 expression subset may have a poor
      prognosis. In human myeloma cell lines, the 17-kb 5' upstream enhancer and the
      promoter region of the PU.1 gene were highly methylated, and this is consistent
      with disappearance of DNase I-hypersensitive sites in these regions. To elucidate
      the significance of down-regulation of PU.1, we generated stable myeloma cell
      lines with an inducible PU.1 expression system. Exogenous expression of PU.1 in
      PU.1 null myeloma cell lines, U266 and KMS12PE, induced complete growth arrest
      and cell death. Up-regulation of PU.1 by 5-aza-2'-deoxycytidine also induced
      growth arrest of KMS12PE and KHM11 myeloma cells. These data suggest that down
      regulation of PU.1 is an essential step for the survival of a subset of myeloma
      cells and that up-regulation of PU.1 by demethylation agents or other types of
      agents may represent a new therapeutic strategy for treatment of multiple myeloma
      patients.

PMID- 17545614
TI  - Estrogen receptor alpha mediates breast cancer cell resistance to paclitaxel
      through inhibition of apoptotic cell death.
AB  - Estrogen receptors (ER) are expressed in approximately 65% of human breast
      cancer. Cumulative data from clinical trials and retrospective analyses suggest
      that some chemotherapeutic agents may be less effective in patients with ER
      positive (ER+) tumors than those with ER-negative (ER-) tumors. Paclitaxel is an
      active agent used in breast cancer chemotherapy. To investigate the possible
      influence of ER on the therapeutic efficacy of paclitaxel and its underlying
      mechanism, we established several isogenic ER+ cell lines by stable transfection
      of ERalpha expression vectors into ER- breast cancer BCap37 cells. We showed that
      17-beta estradiol significantly reduces the overall cytotoxicity of paclitaxel in
      BCap37-expressing ERalpha but has no influence on the ER- parental cells. Further
      analyses indicate that expression of ERalpha in BCap37 cells mainly interferes
      with paclitaxel-induced apoptotic cell death, without affecting paclitaxel
      induced microtubule bundling and mitotic arrest. Moreover, we found that the
      addition of ICI 182,780 (Fulvestrant), a selective ER down-regulator, could
      completely reverse the resistance of ER+ BCap37 cells to paclitaxel. These
      findings showed that ERalpha-mediated breast tumor cell resistance to paclitaxel
      was through selective inhibition of paclitaxel-induced tumor cell apoptosis.
      Additionally, the combination of ICI 182,780 also sensitizes MCF-7 and T47D cell
      lines to the treatment of paclitaxel, which further confirmed the correlation
      between ERalpha and drug resistance in ER+ tumor cells. The results obtained from
      this study provide useful information for understanding ER-mediated resistance to
      paclitaxel and possibly other antineoplastic agents.

PMID- 17545615
TI  - Therapeutic efficacy of replication-competent retrovirus vector-mediated suicide
      gene therapy in a multifocal colorectal cancer metastasis model.
AB  - Replication-competent retrovirus (RCR) vectors are intrinsically incapable of
      infecting quiescent cells and have been shown to achieve highly efficient and
      tumor-restricted replicative spread and gene transfer in vivo after direct
      intratumoral injection in a variety of primary cancer models. However, i.v.
      delivery of RCR vectors expressing therapeutic genes has never previously been
      tested, particularly in an immunocompetent tumor model. Therefore, in the present
      study, we sought to test the therapeutic effect of an RCR vector (ACE-CD)
      carrying the yeast cytosine deaminase (CD) gene, which converts the nontoxic
      prodrug 5-fluorocytosine (5FC) into the chemotoxin 5-fluorouracil, after delivery
      by infusion into the locoregional circulation in a multifocal hepatic metastasis
      model of colon cancer. After confirmation of suicide gene cytotoxicity in vitro,
      multifocal hepatic tumors were established in syngeneic mice with murine CT26
      colorectal cancer cells expressing firefly luciferase (CT26-Luc), and the ACE-CD
      vector was infused via intrasplenic injection into the portal circulation.
      Fourteen days after locoregional infusion, systemic administration of 5FC
      resulted in significant inhibition of bioluminescent signals in mice whose tumors
      had been infected with RCR but not in control mice. Notably, there was no
      detectable RCR vector spread to normal liver or bone marrow by quantitative PCR
      analysis. Our results thus show that locoregional delivery of a suicide gene by
      RCR vectors infused into the portal circulation results in progressive
      transduction of multiple tumor foci in the liver, without evidence of spread to
      adjacent normal parenchyma or extrahepatic tissues, and can achieve significant
      tumor growth inhibition.

PMID- 17545616
TI  - Adenovirus tumor targeting and hepatic untargeting by a coxsackie/adenovirus
      receptor ectodomain anti-carcinoembryonic antigen bispecific adapter.
AB  - Adenovirus vectors have a number of advantages for gene therapy. However, because
      of their lack of tumor tropism and their preference for liver infection following
      systemic administration, they cannot be used for systemic attack on metastatic
      disease. Many epithelial tumors (e.g., colon, lung, and breast) express
      carcinoembryonic antigen (CEA). To block the natural hepatic tropism of
      adenovirus and to "retarget" the virus to CEA-expressing tumors, we used a
      bispecific adapter protein (sCAR-MFE), which fuses the ectodomain of the
      coxsackie/adenovirus receptor (sCAR) with a single-chain anti-CEA antibody (MFE
      23). sCAR-MFE untargets adenovirus-directed luciferase transgene expression in
      the liver by >90% following systemic vector administration. Moreover, sCAR-MFE
      can "retarget" adenovirus to CEA-positive epithelial tumor cells in cell culture,
      in s.c. tumor grafts, and in hepatic tumor grafts. The sCAR-MFE bispecific
      adapter should, therefore, be a powerful agent to retarget adenovirus vectors to
      epithelial tumor metastases.

PMID- 17545617
TI  - Localization of human TACC3 to mitotic spindles is mediated by phosphorylation on
      Ser558 by Aurora A: a novel pharmacodynamic method for measuring Aurora A
      activity.
AB  - Aurora A is a serine/threonine protein kinase essential for normal mitotic
      progression. Aberrant increased expression of Aurora A, which occurs frequently
      in human cancers, results in abnormal mitoses leading to chromosome instability
      and possibly tumorigenesis. Consequently, Aurora A has received considerable
      attention as a potential target for anticancer therapeutic intervention. Aurora A
      coordinates several essential mitotic activities through phosphorylation of a
      variety of proteins, including TACC3, which modulates microtubule stabilization
      of the mitotic spindle. Recent studies identified a conserved serine in Xenopus
      (Ser(626)) and Drosophila (Ser(863)) TACC3 orthologues that is phosphorylated by
      Aurora A. We show that this conserved serine on human TACC3 (Ser(558)) is also
      phosphorylated by Aurora A. Moreover, phosphorylation of TACC3 by Aurora A in
      human cells is essential for its proper localization to centrosomes and proximal
      mitotic spindles. Inhibition of Aurora A with the selective small molecule
      inhibitor MLN8054 in cultured human tumor cells resulted in mislocalization of
      TACC3 away from mitotic spindles in a concentration-dependent manner.
      Furthermore, oral administration of MLN8054 to nude mice bearing HCT-116 human
      tumor xenografts caused a dose-dependent mislocalization of TACC3 away from
      spindle poles that correlated with tumor growth inhibition. As TACC3 localization
      to mitotic spindles depends on Aurora A-mediated phosphorylation, quantifying
      TACC3 mislocalization represents a novel pharmacodynamic approach for measuring
      Aurora A activity in cancer patients treated with inhibitors of Aurora A kinase.

PMID- 17545618
TI  - The soluble wnt receptor Frizzled8CRD-hFc inhibits the growth of teratocarcinomas
      in vivo.
AB  - Wnt signaling is important for normal cell proliferation and differentiation, and
      mutations in pathway components are associated with human cancers. Recent studies
      suggest that altered wnt ligand/receptor interactions might also contribute to
      human tumorigenesis. Therefore, agents that antagonize wnt signaling at the
      extracellular level would be attractive therapeutics for these cancers. We have
      generated a soluble wnt receptor comprising the Frizzled8 cysteine-rich domain
      (CRD) fused to the human Fc domain (F8CRDhFc) that exhibits favorable
      pharmacologic properties in vivo. Potent antitumor efficacy was shown using the
      mouse mammary tumor virus-Wnt1 tumor model under dosing conditions that did not
      produce detectable toxicity in regenerating tissue compartments. In vitro,
      F8CRDhFc inhibited autocrine wnt signaling in the teratoma cell lines PA-1, NTera
      2, Tera-2, and NCCIT. In vivo, systemic administration of F8CRDhFc significantly
      retarded the growth of tumor xenografts derived from two of these cell lines, PA
      1 and NTera-2. Pharmacodynamic markers of wnt signaling, identified by gene
      expression analysis of cultured teratoma cells, were also modulated in the tumor
      xenografts following treatment with F8CRDhFc. Additionally, these markers could
      be used as indicators of treatment efficacy and might also be useful in
      identifying patients that would benefit from the therapeutic agent. This is the
      first report showing the efficacy of a soluble wnt receptor as an antitumor agent
      and suggests that further development of wnt antagonists will have utility in
      treating human cancer.

PMID- 17545619
TI  - NRH:quinone oxidoreductase 2 and NAD(P)H:quinone oxidoreductase 1 protect tumor
      suppressor p53 against 20s proteasomal degradation leading to stabilization and
      activation of p53.
AB  - Tumor suppressor p53 is either lost or mutated in several types of cancer. MDM2
      interaction with p53 results in ubiquitination and 26S proteasomal degradation of
      p53. Chronic DNA damage leads to inactivation of MDM2, stabilization of p53, and
      apoptotic cell death. Here, we present a novel MDM2/ubiquitination-independent
      mechanism of stabilization and transient activation of p53. The present studies
      show that 20S proteasomes degrade p53. The 20S degradation of p53 was observed in
      ubiquitin-efficient and -deficient cells, indicating that this pathway of
      degradation did not require ubiquitination of p53. The cytosolic quinone
      oxidoreductases [NRH:quinone oxidoreductase 2 (NQO2) and NAD(P)H:quinone
      oxidoreductase 1 (NQO1)] interacted with p53 and protected p53 against 20S
      proteasomal degradation. Further studies revealed that acute exposure to
      radiation or chemical leads to induction of NQO1 and NQO2 that stabilizes and
      transiently activates p53 and downstream genes. These results suggest that stress
      induced NQO1 and NQO2 transiently stabilize p53, which leads to protection
      against adverse effects of stressors.

PMID- 17545620
TI  - Regression of early and intermediate stages of colon cancer by targeting multiple
      members of the EGFR family with EGFR-related protein.
AB  - A role of the epidermal growth factor receptor (EGFR) family has been suggested
      in colon cancer etiology, progression, and/or severity. Our recently identified
      pan-erbB inhibitor EGFR-related protein (ERRP) targets EGFRs by attenuating their
      activation and subsequent signaling leading to cellular growth inhibition. In the
      present study, we evaluated the therapeutic effectiveness of ERRP on early and
      intermediate stages of colon cancer by examining regression of chemically induced
      aberrant crypt foci (ACF) in the colon of CF1 mice and intestinal adenomas in
      APC(Min+/-) (Min) mice. After formation of ACF or adenomas, the mice were
      injected (i.p.) with ERRP (50 microg/mouse) for 10 consecutive days. This
      treatment significantly reduced the number of ACF from 25.0 +/- 3.0 (controls) to
      14.9 +/- 1.6 (ERRP-treated; P = 0.011) and also reduced their size (P < 0.01). In
      Min mice, ERRP caused the regression of adenomas throughout the small intestine
      (P < 0.05) and reduced their size (P < 0.001). This could partly be attributed to
      inhibition of proliferation and stimulation of apoptosis in the intestinal mucosa
      and was associated with decreased activation of several EGFR family members,
      suppression of downstream effector nuclear factor kappaB and down-regulation of
      cyclooxygenase-2. ERRP-induced attenuation of EGFR activation could be due to
      increased sequestration of the ligand(s) by ERRP, rendering them unavailable for
      binding to and activation of the receptor. In conclusion, our data show that ERRP
      is effective in regressing both early and intermediate intestinal lesions and
      could be an effective therapeutic agent for colon cancer.

PMID- 17545621
TI  - Sequential treatment by ionizing radiation and sodium arsenite dramatically
      accelerates TRAIL-mediated apoptosis of human melanoma cells.
AB  - Melanoma is the most lethal form of skin cancer. There is a lack of effective
      treatments for individuals with advanced disease. Many melanomas exhibit high
      levels of radioresistance. The direct consequence of gamma-irradiation for most
      melanoma cells is growth arrest at the G2-M phase of cell cycle. However,
      radiation-induced signaling pathways may affect numerous additional targets in
      cancer cells. We show in the present study that gamma-irradiation, as well as
      alpha-particle exposure, dramatically increases the susceptibility of melanoma
      cells to recombinant tumor necrosis factor-related apoptosis-inducing ligand
      (TRAIL)-mediated apoptosis via up-regulation of surface TRAIL-receptor 1/receptor
      2 (DR4/DR5) levels and to Fas ligand-mediated apoptosis via up-regulation of
      surface Fas levels. Additionally, increased dynamin-2 expression after
      irradiation is critically important in the translocation of death receptor to the
      cell surface. Moreover, sodium arsenite treatment may up-regulate expression of
      endogenous TRAIL and induces its translocation to cell surface and further down
      regulates cFLIP levels in melanoma cells. We have evaluated the effects of
      sequential gamma-irradiation and arsenite treatment of melanoma cells for the
      induction of death signaling. Such treatment results in an efficient TRAIL
      mediated apoptosis via a paracrine mechanism. These data highlight the efficacy
      of combined modality treatment involving radiation and arsenite in clinical
      management of this often fatal form of skin cancer.

PMID- 17545622
TI  - Proton pump inhibitors induce apoptosis of human B-cell tumors through a caspase
      independent mechanism involving reactive oxygen species.
AB  - Proton pumps like the vacuolar-type H+ ATPase (V-ATPase) are involved in the
      control of cellular pH in normal and tumor cells. Treatment with proton pump
      inhibitors (PPI) induces sensitization of cancer cells to chemotherapeutics via
      modifications of cellular pH gradients. It is also known that low pH is the most
      suitable condition for a full PPI activation. Here, we tested whether PPI
      treatment in unbuffered culture conditions could affect survival and
      proliferation of human B-cell tumors. First, we showed that PPI treatment
      increased the sensitivity to vinblastine of a pre-B acute lymphoblastic leukemia
      (ALL) cell line. PPI, per se, induced a dose-dependent inhibition of
      proliferation of tumor B cells, which was associated with a dose- and time
      dependent apoptotic-like cytotoxicity in B-cell lines and leukemic cells from
      patients with pre-B ALL. The effect of PPI was mediated by a very early
      production of reactive oxygen species (ROS), that preceded alkalinization of
      lysosomal pH, lysosomal membrane permeabilization, and cytosol acidification,
      suggesting an early destabilization of the acidic vesicular compartment.
      Lysosomal alterations were followed by mitochondrial membrane depolarization,
      release of cytochrome c, chromatin condensation, and caspase activation. However,
      inhibition of caspase activity did not affect PPI-induced cell death, whereas
      specific inhibition of ROS by an antioxidant (N-acetylcysteine) significantly
      delayed cell death and protected both lysosomal and mitochondrial membranes. The
      proapoptotic activity of PPI was consistent with a clear inhibition of tumor
      growth following PPI treatment of B-cell lymphoma in severe combined
      immunodeficient mice. This study further supports the importance of acidity and
      pH gradients in tumor cell homeostasis and suggests new therapeutic approaches
      for human B-cell tumors based on PPI.

PMID- 17545623
TI  - Noxa up-regulation and Mcl-1 cleavage are associated to apoptosis induction by
      bortezomib in multiple myeloma.
AB  - Targeting the ubiquitin-proteasome pathway has emerged as a potent anticancer
      strategy. Bortezomib, a specific proteasome inhibitor, has been approved for the
      treatment of relapsed or refractory multiple myeloma. Multiple myeloma cell
      survival is highly dependent on Mcl-1 antiapoptotic molecules. In a recent study,
      proteasome inhibitors induced Mcl-1 accumulation that slowed down their
      proapoptotic effects. Consequently, we investigated the role of Bcl-2 family
      members in bortezomib-induced apoptosis. We found that bortezomib induced
      apoptosis in five of seven human myeloma cell lines (HMCL). Bortezomib-induced
      apoptosis was associated with Mcl-1 cleavage regardless of Mcl-1L accumulation.
      Furthermore, RNA interference mediated Mcl-1 decrease and sensitized RPMI-8226
      HMCL to bortezomib, highlighting the contribution of Mcl-1 in bortezomib-induced
      apoptosis. Interestingly, an important induction of Noxa was found in all
      sensitive HMCL both at protein and mRNA level. Concomitant to Mcl-1 cleavage and
      Noxa induction, we also found caspase-3, caspase-8, and caspase-9 activation.
      Under bortezomib treatment, Mcl-1L/Noxa complexes were highly increased, Mcl
      1/Bak complexes were disrupted, and there was an accumulation of free Noxa.
      Finally, we observed a dissociation of Mcl-1/Bim complexes that may be due to a
      displacement of Bim induced by Noxa. Thus, in myeloma cells, the mechanistic
      basis for bortezomib sensitivity can be explained mainly by the model in which
      the sensitizer Noxa can displace Bim, a BH3-only activator, from Mcl-1, thus
      leading to Bax/Bak activation.

PMID- 17545624
TI  - Mapping genes that contribute to daunorubicin-induced cytotoxicity.
AB  - Daunorubicin is an anthracycline antibiotic agent used in the treatment of
      hematopoietic malignancies. Toxicities associated with this agent include
      myelosuppression and cardiotoxicity; however, the genes or genetic determinants
      that contribute to these toxicities are unknown. We present an unbiased genome
      wide approach that incorporates heritability, whole-genome linkage analysis, and
      linkage-directed association to uncover genetic variants contributing to the
      sensitivity to daunorubicin-induced cytotoxicity. Cell growth inhibition in 324
      Centre d' Etude du Polymorphisme Humain lymphoblastoid cell lines (24 pedigrees)
      was evaluated following treatment with daunorubicin for 72 h. Heritability
      analysis showed a significant genetic component contributing to the cytotoxic
      phenotypes (h2 = 0.18-0.63 at 0.0125, 0.025, 0.05, 0.1, 0.2, and 1.0 mumol/L
      daunorubicin and at the IC50, the dose required to inhibit 50% cell growth).
      Whole-genome linkage scans at all drug concentrations and IC50 uncovered 11
      regions with moderate peak LOD scores (> 1.5), including 4q28.2 to 4q32.3 with a
      maximum LOD score of 3.18. The quantitative transmission disequilibrium tests
      were done using 31,312 high-frequency single-nucleotide polymorphisms (SNP)
      located in the 1 LOD confidence interval of these 11 regions. Thirty genes were
      identified as significantly associated with daunorubicin-induced cytotoxicity (P
      < or = 2.0 x 10(-4), false discovery rate < or = 0.1). Pathway and functional
      gene ontology analysis showed that these genes were overrepresented in the
      phosphatidylinositol signaling system, axon guidance pathway, and GPI-anchored
      proteins family. Our findings suggest that a proportion of susceptibility to
      daunorubicin-induced cytotoxicity may be controlled by genetic determinants and
      that analysis using linkage-directed association studies with dense SNP markers
      can be used to identify the genetic variants contributing to cytotoxicity.

PMID- 17545625
TI  - Eradication of therapy-resistant human prostate tumors using a cancer terminator
      virus.
AB  - Terminal prostate cancer is refractory to conventional anticancer treatments
      because of frequent overexpression of antiapoptotic proteins Bcl-2 and/or Bcl
      x(L). Adenovirus-mediated delivery of melanoma differentiation associated gene
      7/interleukin-24 (mda-7/IL-24), a secreted cytokine having cancer-selective
      apoptosis-inducing properties, profoundly inhibits prostate cancer cell growth.
      However, forced overexpression of Bcl-2 or Bcl-x(L) renders prostate cancer cells
      resistant to Ad.mda-7. We constructed a conditionally replication-competent
      adenovirus in which expression of the adenoviral E1A gene, necessary for
      replication, is driven by the cancer-specific promoter of progression elevated
      gene-3 (PEG-3) and which simultaneously expresses mda-7/IL-24 in the E3 region of
      the adenovirus (Ad.PEG-E1A-mda-7), a cancer terminator virus (CTV). This CTV
      generates large quantities of MDA-7/IL-24 as a function of adenovirus replication
      uniquely in cancer cells. Infection of Ad.PEG-E1A-mda-7 (CTV) in normal prostate
      epithelial cells and parental and Bcl-2- or Bcl-x(L)-overexpressing prostate
      cancer cells confirmed cancer cell-selective adenoviral replication, mda-7/IL-24
      expression, growth inhibition, and apoptosis induction. Injecting Ad.PEG-E1A-mda
      7 (CTV) into xenografts derived from DU-145-Bcl-x(L) cells in athymic nude mice
      completely eradicated not only primary tumors but also distant tumors
      (established in the opposite flank), thereby implementing a cure. These
      provocative findings advocate potential therapeutic applications of this novel
      virus for advanced prostate cancer patients with metastatic disease.

PMID- 17545626
TI  - A combination hybrid-based vaccination/adoptive cellular therapy to prevent tumor
      growth by involvement of T cells.
AB  - Cancer immunotherapy with dendritic cell-tumor cell fusion hybrids induces
      polyclonal stimulation against a variety of tumor antigens, including unknown
      antigens. Hybrid cells can prime CTLs, which subsequently develop antitumor
      responses. The aim of this study was to enhance the known antitumor effect of
      hybrid vaccination (HC-Vacc) and hybrid-primed adoptive T-cell therapy (HC-ACT)
      using the poorly immunogenic Lewis lung carcinoma (LLC1) model. The strategy used
      was a combination of a double HC-Vacc alternating with HC-ACT (HC-Vacc/ACT).
      Using flat-panel volumetric computer tomography and immunohistochemistry, we
      showed a significant retardation of tumor growth (85%). In addition, a
      significant delay in tumor development, a reduction in the number of pulmonary
      metastases, and increased survival times were observed. Furthermore, the tumors
      displayed significant morphologic changes and increased apoptosis, as shown by up
      regulation of gene expression of the proapoptotic markers Fas, caspase-8, and
      caspase-3. The residual tumor masses seen in the HC-Vacc/ACT-treated mice were
      infiltrated with CD4+ and CD8+ lymphocytes and showed elevated IFNgamma
      expression. Moreover, splenic enlargement observed in HC-Vacc/ACT-treated mice
      reflected the increased functionality of T cells, as also indicated by increased
      expression of markers for CTL activation, differentiation, and proliferation
      (Cd28, Icosl, Tnfrsf13, and Tnfsf14). Our findings indicate that the combination
      therapy of dendritic cell-tumor cell HC-Vacc/ACT is a very effective and a
      promising immunotherapeutic regimen against poorly immunogenic carcinomas.

PMID- 17545627
TI  - Host perforin reduces tumor number but does not increase survival in oncogene
      driven mammary adenocarcinoma.
AB  - The concept of tumor immune surveillance has been supported by several recent
      studies in mice which show that immune effector mechanisms suppress hematologic
      malignancy. However, because the most common forms of human cancer are epithelial
      in origin, and comparatively very little data supports the immune surveillance of
      epithelial malignancies, we have chosen to evaluate the role of perforin-mediated
      cytotoxicity in the prevention of BALB/c Her2/neu-induced mammary cancer.
      Interestingly, perforin significantly delayed the onset of mammary tumorigenesis
      and reduced the number of mammary tumors without improving survival. Natural
      killer cell, but not CD8+ T cell, depletion resulted in a similar phenotype to
      perforin deficiency in this regard. Histologic analysis further indicated that
      the effect of perforin was most evident during the earliest stages of
      carcinogenesis rather than prior to or during the hyperplastic phase. This data
      suggests that perforin may mediate some suppression of epithelial carcinogenesis
      by intervening early in the tumor development process.

PMID- 17545628
TI  - Epigenetically controlled fibroblast growth factor receptor 2 signaling imposes
      on the RAS/BRAF/mitogen-activated protein kinase pathway to modulate thyroid
      cancer progression.
AB  - Fibroblast growth factor (FGF) signals play fundamental roles in development and
      tumorigenesis. Thyroid cancer is an example of a tumor with nonoverlapping
      genetic mutations that up-regulate mitogen-activated protein kinase (MAPK). Here,
      we show that FGF receptor 1 (FGFR1), which is expressed mainly in neoplastic
      thyroid cells, propagates MAPK activation and promotes tumor progression. In
      contrast, FGFR2 is down-regulated in neoplastic thyroid cells through DNA
      promoter methylation. Reexpression of FGFR2 competes with FGFR1 for the immediate
      substrate FGFR substrate 2 to impede signaling upstream of the BRAF/MAPK pathway.
      These data unmask an epigenetically controlled FGFR2 signal that imposes
      precisely on the intragenically modified BRAF/MAPK pathway to modulate thyroid
      cancer behavior.

PMID- 17545629
TI  - Expression and functional analysis of human leukocyte antigen class I antigen
      processing machinery in medulloblastoma.
AB  - Defects in the expression and/or function of the human leukocyte antigen (HLA)
      class I antigen-processing machinery (APM) components are found in many tumor
      types. These abnormalities may have a negative impact on the interactions of
      tumor cells with host's immune system and on the outcome of T cell-based
      immunotherapy. To the best of our knowledge, no information is available about
      APM component expression and functional characteristics in human medulloblastoma
      cells (Mb). Therefore, in the present study, we have initially compared the
      expression of APM components in Mb, an embryonal pediatric brain tumor with a
      poor prognosis, with that in noninfiltrating astrocytic pediatric tumors, a group
      of differentiated brain malignancies with favorable prognosis. LMP2, LMP7,
      calnexin, beta2-microglobulin-free heavy chain (HC) and beta2-microglobulin were
      down-regulated or undetectable in Mb lesions, but not in astrocytic tumors or
      normal fetal cerebellum. Two Mb cell lines (DAOI and D283) displayed similar but
      not superimposable defects in APM component expression as compared with primary
      tumors. To assess the functional implications of HLA class I APM component down
      regulation in Mb cell lines, we tested their recognition by HLA class I antigen
      restricted, tumor antigen (TA)-specific CTL, generated by stimulations with
      dendritic cells that had been transfected with Mb mRNA. The Mb cell lines were
      lysed by TA-specific CTL in a HLA-restricted manner. Thus, defective expression
      of HLA class I-related APM components in Mb cells does not impair their ability
      to present TA to TA-specific CTL. In conclusion, these results can contribute to
      optimize T cell-based immunotherapeutic strategies for Mb treatment.

PMID- 17545630
TI  - Elevated interleukin-6 and G-CSF in human pancreatic cancer cell conditioned
      medium suppress dendritic cell differentiation and activation.
AB  - Although dendritic cell (DC) function is impaired in pancreatic cancer patients,
      the underlying mechanisms are unknown. This study analyzed the soluble factors
      released by pancreatic cancer cells responsible for inhibiting DC differentiation
      and activation. Medium conditioned by a highly metastatic human pancreatic cancer
      cell line BxPC-3 [BxPC-3 conditioned medium (BxCM)] was mainly used for the
      study. Both CD34+ hematopoietic progenitor cell-derived and CD14+ monocyte
      derived immature DCs and mature DCs (mDCs) were inhibited by BxCM.
      Allostimulation of CD4+ and CD8+ T cells by BxCM-treated mDCs was inefficient and
      resulted in production of lower levels of Th1 and Th2 cytokines. Antigen-specific
      T-cell activation capability was also reduced in BxCM-treated mDCs. Addition of
      exogenous interleukin-6 (IL-6) and granulocyte colony-stimulating factor (G-CSF),
      which were present in high amounts in BxCM, mimicked the inhibitory effect of
      BxCM on DC differentiation and maturation. IL-6 was able to suppress DC
      differentiation and G-CSF mainly acted on the suppressing allostimulatory
      capacity of DCs. In addition, pancreatic cancer patient sera were able to inhibit
      DC differentiation of CD14+ monocytes obtained from healthy donors. Depleting IL
      6 or G-CSF from BxCM could reverse the DC-inhibitory properties of BxCM.
      Furthermore, BxCM, IL-6, or G-CSF led to the activation of signal transducer and
      activator of transcription 3 (STAT3) in CD14+ monocytes to different degrees.
      Blocking BxCM-induced STAT3 activation also reversed the inhibitory effect of
      BxCM on DC differentiation. Therefore, IL-6 and G-CSF in BxCM represent two main
      factors responsible for suppression of DC differentiation, maturation, and
      antigen presentation, and this suppression of DC functions may be due to the
      aberrant activation of STAT3 by BxCM.

PMID- 17545631
TI  - BCR-ABL activity is critical for the immunogenicity of chronic myelogenous
      leukemia cells.
AB  - Chronic myelogenous leukemia (CML) is a myeloproliferative disorder caused by
      excessive granulopoiesis due to the formation of the constitutively active
      tyrosine kinase BCR-ABL. An effective drug against CML is imatinib mesylate, a
      tyrosine kinase inhibitor acting on Abl kinases, c-KIT, and platelet-derived
      growth factor receptor. Recently, a study revealed that patients treated with
      imatinib showed impaired CTL responses compared with patients treated with IFN
      alpha, which might be due to a treatment-induced reduction in immunogenicity of
      CML cells or immunosuppressive effects. In our study, we found that inhibition of
      BCR-ABL leads to a down-regulation of immunogenic antigens on the CML cells in
      response to imatinib treatment, which results in the inhibition of CML-directed
      immune responses. By treating CML cells with imatinib, we could show that the
      resulting inhibition of BCR-ABL leads to a decreased expression of tumor
      antigens, including survivin, adipophilin, hTERT, WT-1, Bcl-x(L), and Bcl-2 in
      correlation to a decreased development of CML-specific CTLs. In contrast, this
      reduction in immunogenicity was not observed when a CML cell line resistant to
      the inhibitory effects of imatinib was used, but could be confirmed by
      transfection with specific small interfering RNA against BCR-ABL or imatinib
      treatment of primary CML cells.

PMID- 17545632
TI  - Recognition of prostate and melanoma tumor cells by six-transmembrane epithelial
      antigen of prostate-specific helper T lymphocytes in a human leukocyte antigen
      class II-restricted manner.
AB  - The six-transmembrane epithelial antigen of prostate (STEAP) protein is an
      attractive candidate for T cell-based immunotherapy because it is overexpressed
      in prostate cancer and various other tumor types. Several peptide epitopes
      capable of stimulating CTLs that killed STEAP-expressing tumor cells have been
      described. Our goal was the identification of helper T lymphocyte (HTL) epitopes
      of STEAP for the optimization of T cell-based immunotherapies against STEAP
      expressing malignancies. Candidate HTL epitopes for STEAP were predicted using in
      silico algorithms for HLA class II-binding peptides and were tested for their
      ability to elicit HTL responses by in vitro peptide vaccination of CD4 T
      lymphocytes from healthy individuals and prostate cancer patients. Two peptides
      (STEAP(102-116) and STEAP(192-206)) were effective in stimulating in vitro
      antitumor HTL responses in both normal individuals and prostate cancer patients.
      Notably, both STEAP HTL peptides behaved as promiscuous T-cell epitopes because
      they stimulated T cells in the context of more than one MHC class II allele.
      These newly described STEAP HTL epitopes could be of value for the design and
      optimization of T cell-based immunotherapy against STEAP-expressing tumors.

PMID- 17545633
TI  - Oncogenic potential of the nuclear receptor coregulator proline-, glutamic acid-,
      leucine-rich protein 1/modulator of the nongenomic actions of the estrogen
      receptor.
AB  - Proline-, glutamic acid-, leucine-rich protein 1 (PELP1), a novel nuclear
      receptor coactivator, and its expression is deregulated in hormone-dependent
      cancers, including those of the breast, endometrium, and ovary. PELP1 interacts
      with estrogen receptor and modulates its genomic and nongenomic functions. In
      this study, we examined whether PELP1 functions as an oncogene. The
      overexpression of PELP1 in fibroblasts and epithelial model cells resulted in
      cellular transformation. PELP1 also enhanced the transformation potential of c
      Src kinase in focus formation assays, and PELP1 overexpression potentiated
      estradiol-mediated cell migratory potential and anchorage-independent growth.
      Using PELP1-small interfering RNA, we provided evidence that endogenous PELP1
      plays an essential role in E2-mediated anchorage-independent growth, cell
      migration, and cytoskeletal changes. When compared with control vector
      transfectants, breast cancer cells stably overexpressing PELP1 showed a rapid
      tumor growth in xenograft studies. Immunohistochemical analysis of PELP1
      expression using a tumor progression array of 252 breast carcinomas and normal
      breast tissue specimens revealed that PELP1 expression is deregulated to a
      greater degree in higher grade node-positive invasive tumors than in normal
      breast tissue or ductal carcinoma in situ. Our data suggest that PELP1 is a
      potential oncogene, that its expression is deregulated during cancer progression,
      and that PELP1 may play a role in oncogenesis.

PMID- 17545634
TI  - Differential regulation of estrogen receptor alpha turnover and transactivation
      by Mdm2 and stress-inducing agents.
AB  - In mammalian cells, the level of estrogen receptor alpha (ERalpha) is rapidly
      decreased upon estrogen treatment, and this regulation involves proteasome
      degradation. Using different approaches, we showed that the Mdm2 oncogenic
      ubiquitin-ligase directly interacts with ERalpha in a ternary complex with p53
      and is involved in the regulation of ERalpha turnover (both in the absence or
      presence of estrogens). Several lines of evidence indicated that this effect of
      Mdm2 required its ubiquitin-ligase activity and involved the ubiquitin/proteasome
      pathway. Moreover, in MCF-7 human breast cancer cells, various p53-inducing
      agents (such as UV irradiation) or treatment with RITA (which inhibits the
      interaction of p53 with Mdm2) stabilized ERalpha and abolished its 17beta
      estradiol-dependent turnover. Interestingly, our data indicated that ligand
      dependent receptor turnover was not required for efficient transactivation.
      Altogether, our results indicate that the Mdm2 oncoprotein and stress-inducing
      agents complexly and differentially regulate ERalpha stability and
      transcriptional activity in human cancer cells.

PMID- 17545635
TI  - MUC1 oncoprotein promotes refractoriness to chemotherapy in thyroid cancer cells.
AB  - Overexpression of MUC1 oncoprotein is frequently observed in cancer and
      contributes to confer resistance to genotoxic agents. Papillary, follicular, and
      anaplastic thyroid carcinomas are the three forms of thyroid epithelial cancer.
      Anaplastic tumors are less differentiated and extremely aggressive, characterized
      by a poor prognosis. Little is known about the role of MUC1 in thyroid cancer. We
      recently showed that autocrine production of interleukin (IL)-4 and IL-10
      controls thyroid cancer cell survival, growth, and resistance to chemotherapy
      through activation of Janus-activated kinase/signal transducers and activators of
      transcription (JAK/STAT) and phosphatidylinositide 3'-OH kinase (PI3K)/Akt
      pathways. In the present study, we showed that MUC1 COOH-terminal subunit (MUC1
      C) is overexpressed in all the histologic variants of thyroid cancer cells and
      localizes to mitochondria where it interferes with the release of mitochondrial
      proapoptotic proteins. Moreover, IL-4 and IL-10 promote the increase of MUC1-C
      expression levels in normal thyroid cells, whereas blockage of both cytokines or
      neutralization of JAK/STAT and PI3K/Akt pathways through the exogenous expression
      of SOCS-1 and Akt(K179M) leads to a significant decrease of MUC1-C in primary
      thyroid cancer cells. Interestingly, down-regulation of MUC1 expression by direct
      targeting with RNA interference sensitizes anaplastic thyroid cancer cells to
      chemotherapy-induced apoptosis in vitro. Thus, MUC1 is a main component of the
      survival network acting in thyroid cancer and could be considered a key molecular
      target for sensitizing cancer cells to conventional or novel treatments.

PMID- 17545636
TI  - Mechanism of increased lipolysis in cancer cachexia.
AB  - Loss of fat mass is a key feature of cancer cachexia and has been attributed to
      increased adipocyte lipolysis. The mechanism behind this alteration is unknown
      and was presently investigated. We studied mature s.c. fat cells and
      differentiated preadipocytes from 26 cancer patients with and without cachexia.
      Hormone-induced lipolysis and expression of lipolysis-regulating genes were
      determined together with body composition and in vivo lipolytic activity (fasting
      plasma glycerol or fatty acids related to body fat). Body fat was reduced by 40%
      and in vivo lipolytic activity was 2-fold increased in cachexia (P = 0.001). In
      mature adipocytes, the lipolytic effects of catecholamines and natriuretic
      peptide were 2- to 3-fold increased in cachexia (P < 0.001). This was completely
      counteracted by inhibiting the rate-limiting lipolysis enzyme hormone-sensitive
      lipase (HSL). In cachexia, the expression levels of HSL mRNA and protein were
      increased by 50% and 100%, respectively (P = 0.005-0.03), which strongly
      correlated with in vitro lipolytic stimulation (r = 0.7-0.9). The antilipolytic
      effect of insulin in mature fat cells and the stimulated lipolytic effect in
      differentiated preadipocytes were unaltered in cachexia. Patients who lost weight
      due to other factors than cancer cachexia had no change in adipocyte lipolysis.
      In conclusion, adipocyte lipolysis is increased in cancer cachexia not due to
      nonepigenic factors or to weight loss per se, but most probably because of
      enhanced expression and function of adipocyte HSL. The selective inhibition of
      this enzyme may prevent fat loss in cancer patients.

PMID- 17545637
TI  - Short telomere length and breast cancer risk: a study in sister sets.
AB  - Telomeres consist of a tandem repeats of the sequence TTAGGG at the ends of
      chromosomes and play a key role in the maintenance of chromosomal stability.
      Previous studies indicated that short telomeres are associated with increased
      risk for human bladder, head and neck, lung, and renal cell cancer. We
      investigated the association between white blood cell telomere length and breast
      cancer risk among 268 family sets (287 breast cancer cases and 350 sister
      controls). Telomere length was assessed by quantitative PCR. The mean telomere
      length was shorter in cases (mean, 0.70; range, 0.03-1.95) than in unaffected
      control sisters (mean, 0.74; range, 0.03-2.29), but no significant difference was
      observed (P = 0.11). When subjects were categorized according to the median
      telomere length in controls (0.70), affected sisters had shorter telomeres
      compared with unaffected sisters after adjusting for age at blood donation and
      smoking status [odds ratio (OR), 1.3; 95% confidence interval (95% CI), 0.9-1.8],
      but the association was not statistically significant. The association by
      quartile of telomere length (Q4 shortest versus Q1 longest) also supported an
      increase in risk from shorter telomere length, although the association was not
      statistically significant (OR, 1.6; 95% CI, 0.9-2.7). This association was more
      pronounced among premenopausal women (OR, 2.1; 95% CI, 0.8-5.5) than
      postmenopausal women (OR, 1.3; 95% CI, 0.5-3.6 for Q4 versus Q1). If these
      associations are replicated in larger studies, they provide modest epidemiologic
      evidence that shortened telomere length may be associated with breast cancer
      risk.

PMID- 17545638
TI  - Polychlorinated biphenyl levels in peripheral blood and non-Hodgkin's lymphoma: a
      report from three cohorts.
AB  - The incidence of non-Hodgkin's lymphoma (NHL) unrelated to HIV infection has
      steadily increased over the past several decades and remains substantially
      unexplained. Limited evidence suggests that increased concentrations of
      polychlorinated biphenyls (PCB) measured in blood or fat tissue are associated
      with increased risk of NHL. Although PCB congeners vary in their biological
      activity, the relation between individual congeners and NHL risk has not been
      examined previously using prospectively collected biospecimens. We examined
      congener-specific associations in three prospective cohorts. Prediagnostic serum
      or plasma concentrations of selected PCB congeners were measured among NHL cases
      and controls from these cohorts: Janus (190 cases and 190 controls) in Norway and
      CLUE I (74 cases and 147 controls) and the Nurses' Health Study (30 cases and 78
      controls) in the United States. All blood samples were collected in the 1970s or
      1980s. We used logistic regression to calculate odds ratios (OR) and 95%
      confidence intervals (95% CI) for the relations between risk of NHL and lipid
      corrected plasma or serum concentrations. Several congeners (i.e., 118, 138, and
      153) that were present at higher levels and were moderately to highly correlated
      with each other showed exposure-response trends with risk of NHL in all three
      cohorts. These associations were observed primarily among subjects diagnosed
      closer to the date of blood collection in the two cohorts with sufficient cases
      to permit stratification by time. Among cases diagnosed within the median years
      of follow-up (16 years in Janus and 12 years in CLUE I), ORs and 95% CIs for
      increasing fourths of concentration of congener 118 relative to the lowest fourth
      were as follows: 2.4 (0.9-6.5), 4.9 (1.6-15.3), and 5.3 (1.5-18.8; P(trend) <
      0.005) in Janus and 8.1 (1.0-68.9), 6.6 (0.7-59.0), and 13.0 (1.6-106.8; P(trend)
      < 0.05) in CLUE I. Similar patterns were seen for congeners 138 and 153 and for
      total PCBs. Limited evidence of exposure-response trends was also observed for
      several other congeners. The primary 1,1,1-trichloro-2,2-bis(p
      chlorophenyl)ethane metabolite, p,p'-DDE, was not significantly associated with
      NHL in most analyses but slightly to moderately confounded the PCB associations.
      The results from these three cohorts suggest that concentrations of certain PCBs
      in blood are associated with increased risk of NHL.

PMID- 17545639
TI  - Plasma folate, vitamin B6, vitamin B12, and homocysteine and pancreatic cancer
      risk in four large cohorts.
AB  - Folate deficiency induces DNA breaks and may alter cellular capacity for mutation
      and epigenetic methylation. Few studies have examined the influence of one-carbon
      nutrients on pancreatic cancer risk, although recent studies suggest a potential
      protective effect for one-carbon nutrients from food sources, but not from
      supplements. We conducted a prospective nested case-control study to examine
      plasma concentrations of folate, vitamin B6 [whose main circulating form is
      pyridoxal-5'-phosphate (PLP)], vitamin B12, and homocysteine in relationship to
      pancreatic cancer, using four large prospective cohorts. Multivariable adjusted
      odds ratios (OR) and 95% confidence intervals (95% CI) were calculated using
      conditional logistic regression. All statistical tests were two sided. Among 208
      cases and 623 controls, we observed no association between folate, PLP, vitamin
      B12, or homocysteine and pancreatic cancer risk. Comparing the highest to lowest
      quartiles of plasma concentration, the ORs were 1.20 (95% CI, 0.76-1.91) for
      folate, 0.80 (95% CI, 0.51-1.25) for B6, 0.91 (95% CI, 0.57-1.46) for B12, and
      1.43 (95% CI, 0.90-2.28) for homocysteine. In analyses restricted to nonusers of
      multivitamins, we observe a modest inverse trend between folate, PLP, and B12 and
      pancreatic cancer risk. In contrast, no such inverse associations were observed
      among study subjects who reported multivitamin supplement use. Among all
      participants, plasma levels of folate, B6, B12, and homocysteine were not
      associated with a significant reduction in the risk of pancreatic cancer. Among
      participants who obtain these factors exclusively through dietary sources, there
      may be an inverse relation between circulating folate, B6, and B12 and risk.

PMID- 17545640
TI  - Docosahexaenoic acid and butyrate synergistically induce colonocyte apoptosis by
      enhancing mitochondrial Ca2+ accumulation.
AB  - We have previously shown that butyrate, a short-chain fatty acid fiber
      fermentation product, induces colonocyte apoptosis via a nonmitochondrial, Fas
      mediated, extrinsic pathway. Interestingly, fermentable fiber when combined with
      fish oil containing docosahexaenoic acid (DHA, 22:6n-3) exhibits an enhanced
      ability to induce apoptosis and protect against colon tumorigenesis. To determine
      the molecular mechanism of action, the effect of DHA and butyrate cotreatment on
      intracellular Ca2+ homeostasis was examined. Mouse colonocytes were treated with
      50 micromol/L DHA or linoleic acid (LA) for 72 h +/- butyrate (0-10 mmol/L) for
      the final 24 h. Cytosolic and mitochondrial Ca2+ levels were measured using Fluo
      4 and Rhod-2. DHA did not alter basal Ca2+ or the intracellular inositol
      trisphosphate (IP3) pool after 6 h butyrate cotreatment. In contrast, at 12 and
      24 h, DHA- and butyrate-treated cultures exhibited a 25% and 38% decrease in
      cytosolic Ca2+ compared with LA and butyrate. Chelation of extracellular Ca2+
      abolished the effect of thapsigargin on the IP3-releasable Ca2+ pool. DHA and
      butyrate cotreatment compared with untreated cells increased the mitochondrial-to
      cytosolic Ca2+ ratio at 6, 12, and 24 h by 73%, 18%, and 37%, respectively. The
      accumulation of mitochondrial Ca2+ preceded the onset of apoptosis. RU-360, a
      mitochondrial-uniporter inhibitor, abrogated mitochondrial Ca2+ accumulation and
      also partially blocked apoptosis in DHA and butyrate cotreated cells.
      Collectively, these data show that the combination of DHA and butyrate, compared
      with butyrate alone, further enhances apoptosis by additionally recruiting a Ca2+
      -mediated intrinsic mitochondrial pathway.

PMID- 17545641
TI  - Induction of apoptosis by celecoxib in cell culture: an uncertain role for
      cyclooxygenase-2.

PMID- 17545642
TI  - A pitfall of propidium iodide staining in fluorescence-activated cell sorting
      cell cycle analysis?

PMID- 17545645
TI  - Spatiotemporal patterns and risks of herd breakdowns in pigs with postweaning
      multisystemic wasting syndrome.
AB  - A retrospective cohort study of 116 British pig farms was undertaken to
      investigate the epidemiological risk factors associated with herd breakdowns with
      postweaning multisystemic wasting syndrome (PMWS). Farmers reported the PMWS
      status of their herd (case definition 1) and, where applicable, when the disease
      was first suspected and what they observed; they described a prolonged increase
      in mortality in six to 16-week-old pigs that was not attributable to any disease
      known to be on their farm. There was over 90 per cent agreement on the farmers'
      PMWS status between the farmers and their veterinarians. Approximately 70 per
      cent of the breakdowns were confirmed at the laboratory (case definition 2)
      except during the outbreak of foot-and-mouth disease (FMD) in 2001 when it was
      reduced to 30 per cent. Porcine circovirus type 2 antigen was detected in pigs
      examined postmortem (case definition 3) in approximately 90 per cent of the farms
      with increased mortality. The breakdowns occurred initially in the south of
      England and spread west and north, as well as locally in a radial pattern from
      the affected farms, and there was strong statistical evidence that there was non
      random space-time clustering. The risk of herd breakdowns with PMWS was not
      constant; therefore, for each case definition, three survival models were
      developed with outcome variable time to breakdown of between January 2000 and
      January 2001, February 2001 to September 2001 (during FMD) or October 2001 to
      December 2003. Exposures with a bivariable significance of P<0.20 were tested in
      three multivariable Cox proportional hazard models. From January 2000 to January
      2001 the risk of a herd breakdown with PMWS for definitions 1, 2 and 3 was
      greater for farms with 600 or more breeding sows, and for definitions 1 and 3
      there was an increased risk associated with the purchase of replacement gilts
      rather than using homebred replacements. For definitions 1 and 3 the farms where
      the nearest pig farm had no breeding pigs were at greater risk of a breakdown
      than those where the nearest farm had breeding stock, as were the farms where
      visitors were not requested to avoid pigs for more than three days before
      visiting the farm during the FMD outbreak. From October 2001, the associated
      risks were identical for all three case definitions; farms were at greater risk
      when they had 600 or more breeding sows, if visitors had not avoided contact with
      pigs for more than three days before visiting the farm, and when there was a farm
      with PMWS less than five miles away. The affected farms were more likely to have
      disease associated with porcine parvovirus, porcine reproduction and respiratory
      syndrome virus, erysipelas, Escherichia coli and salmonella. These exposures were
      positively associated with large herds and the farm being close to other pig
      farms, but did not remain in the final models for breakdown with PMWS, indicating
      that such farms may be at greater risk of many infectious diseases.

PMID- 17545646
TI  - Effects of radial shockwave therapy on the limb function of dogs with hip
      osteoarthritis.
AB  - The objective of this study was to evaluate the effects of extracorporeal radial
      shock wave therapy on the hindlimb function of dogs suffering from hip
      osteoarthritis. Twenty-four client-owned dogs with hip osteoarthritis were
      investigated; 18 of them received radial shockwave therapy and six were left
      untreated as controls. Force plate analysis on a treadmill was used to assess the
      dogs' hindlimb function before treatment and four weeks after the last treatment,
      and the treated dogs were re-evaluated three and six months after the treatment.
      The parameters chosen for evaluation were peak vertical force and vertical
      impulse, and the calculated symmetry indices. In the treated dogs, differences
      between the ground reaction forces exerted by the right and left hindlegs
      disappeared four weeks after the treatment, whereas in the control dogs only the
      peak vertical force distribution changed significantly. The significant
      improvement in the treated dogs was confirmed by changes in the symmetry indices.
      Significant improvements in vertical impulse and peak vertical force were
      observed three months after the treatment.

PMID- 17545647
TI  - Comparison of two doses of ropivacaine for lumbosacral epidural analgesia in
      buffalo calves (Bubalus bubalis).
AB  - Six male buffalo calves aged from six to eight months and weighing 100 to 120 kg
      were used to evaluate the efficacy and safety of caudal epidural analgesia
      produced by doses of 37.5 mg (5 ml) and 75 mg (10 ml) ropivacaine (0.75 per
      cent). The study was completed in two phases. In phase 1, all the animals were
      used twice to evaluate the analgesic and clinical effects of two doses of
      ropivacaine. In phase 2, the animals were divided into two groups of three to
      evaluate the effects of two doses of ropivacaine on some haemodynamic and acid
      base parameters. Signs of analgesia, as evidenced by a loss of response to
      pinprick stimulation, were recorded only at the tail, perineum and hindlimbs of
      the animals given 5 ml ropivacaine, but they extended from the tail to the thorax
      (T9) in the animals given 10 ml ropivacaine. The duration of analgesia was five
      to six hours in the animals given 5 ml ropivacaine and seven to eight hours in
      the animals given 10 ml ropivacaine. Animals of both groups became recumbent, but
      the score for ataxia was higher in the animals given 10 ml ropivacaine. The
      respiratory rate decreased significantly (P<0.05) below the baseline in the
      animals given 10 ml ropivacaine, but the rectal temperature, heart rate, mean
      arterial pressure, central venous pressure and acid-base and electrolyte
      parameters did not change significantly in either group.

PMID- 17545648
TI  - Efficacy of danofloxacin in the treatment of pneumonic pasteurellosis in specific
      pathogen-free lambs.

PMID- 17545649
TI  - Serological evidence for West Nile virus infection in horses in Croatia.

PMID- 17545650
TI  - Sheep ectoparasites in Wales.

PMID- 17545651
TI  - Subacute symmetrical necrotising encephalopathy in young lambs.

PMID- 17545652
TI  - Rabies vaccination.

PMID- 17545653
TI  - Collapsing gun dogs.

PMID- 17545654
TI  - DNA archive for companion animals.

PMID- 17545655
TI  - Inducible supraventricular tachycardias in patients referred for catheter
      ablation of atrial fibrillation.
AB  - AIMS: To investigate the prevalence of underlying, inducible supraventricular
      arrhythmias in patients referred for ablation of atrial fibrillation (AF).
      METHODS AND RESULTS: Electrophysiology study reports of 409 consecutive patients
      (18% female), aged 55 +/- 9 years, who were referred for catheter ablation of AF,
      were studied. At electrophysiology study, arrhythmias other than AF were induced
      in 31 patients (7.6%). Cavotricuspid-dependent atrial flutter was induced in 15
      patients (3.7%), slow-fast atrioventricular nodal re-entrant tachycardia (AVNRT)
      in seven patients (1.7%), atrioventricular re-entrant tachycardia (AVRT) due to
      an accessory pathway in five patients (1.2%), and atrial tachycardia (AT) in four
      patients (0.98%). Specific ablation aimed at elimination of the underlying
      arrhythmia only was performed in 13 patients, isolation of the pulmonary veins
      without additional ablation in three patients, and a combined procedure was
      performed in the remaining 15 patients. No significant association was observed
      between type of induced arrhythmia and type of ablation performed (P = 0.338).
      Slow pathway ablation without pulmonary vein isolation was more common among
      patients with AVNRT (five patients, 71%). AF recurrence was higher among patients
      in whom atrial flutter was induced at electrophysiology study (eight patients,
      53%) compared to those with AVRT (no patient), AT (no patient), or AVNRT (one
      patient) (P = 0.03). CONCLUSION: Patients referred for ablation of paroxysmal AF
      should be investigated for evidence of underlying supraventricular arrhytmias. In
      patients with AVNRT, slow pathway ablation may be the only procedure that is
      necessary for cure of AF. Inducibility of atrial flutter appears to carry an
      increased risk of AF recurrence regardless of whether the cavotricuspid isthmus
      is also ablated.

PMID- 17545656
TI  - The architecture of first trimester chorionic villous vascularization: a confocal
      laser scanning microscopical study.
AB  - BACKGROUND: The aim of this study was to investigate normal chorionic villous
      vascularization using CD31 immunofluorescence and confocal laser scanning
      microscopy (CLSM) to elucidate the spatial arrangement in terms of connections
      between vessels and cords and their branching patterns compared to deficient
      chorionic villous vascularization in complicated pregnancies. METHODS: A
      descriptive morphologic study using CLSM after CD31 immunofluorescence staining
      of placental biopsies from normal pregnancies (n = 20), complete hydatidiform
      molar pregnancies (CHMs; n = 3) and empty sacs (n = 3), with a well documented
      gestational age (GA). RESULTS: In this three-dimensional study, first trimester
      chorionic villi were occupied by a complex network of mainly cords with redundant
      connections as early as 5(+5) weeks GA. With increasing GA cords transform into
      vessels. From about 9 weeks GA onwards, vascular development is characterized by
      the presence of two large vessels located centrally and surrounded by and
      connected to a capillary network. In first trimester CHM and empty sacs, we
      observed a primitive network of mainly cords. CONCLUSIONS: This first
      visualization of the spatio-temporal patterns of blood vessel formation in
      placental villi is characterized by the development of the vasculosyncytial
      membrane from a complex network of cords and can be regarded as the placental
      development before it becomes functional at the end of organogenesis.

PMID- 17545657
TI  - Determination of neutron energy spectra inside a water phantom irradiated by 64
      MeV neutrons.
AB  - A NE230 deuterated liquid scintillator detector (25 mm diameter x 25 mm) has been
      used to investigate neutron energy spectra as a function of position in a water
      phantom under irradiation by a quasi-monoenergetic 64 MeV neutron beam. Neutron
      energy spectra are obtained from measurements of pulse height spectra by the
      NE230 detector using the Bayesian unfolding code MAXED. The experimentally
      measured energy spectra are compared with spectra calculated by Monte Carlo
      simulation using the code MCNPX.

PMID- 17545658
TI  - A non-parametric statistical analysis in the measurement of outdoor gamma
      exposure to the residents around Trombay.
AB  - During this study, non-parametric statistical methods were used to validate the
      measured gamma dose rate with the calculated one, around Trombay. Portable dose
      rate digital gamma spectrometry system (target fieldSPEC) was used for in situ
      measurement of external gamma (gamma) dose rate (measured) with the range of 1
      nSv/h-10 Sv/h. The activity concentration of U-238, Th-232, K-40 and Cs-137 in
      the soil and their respective external dose-conversion factor (nSv/h/Bq/kg) was
      used to evaluate the gamma dose rate (calculated). Non-parametric statistical
      tool like Box- and -Whisker Plot, Spearman's (rho) rank Correlation coefficient,
      the Wilcoxon/Mann-Whitney test and chi(2) distribution test have been applied for
      validation. The randomness or discrete behaviour of measured and calculated dose
      rate was obvious from the Box- and -Whisker Plot as mean and median of the two
      are not equal. The inter quartile range (Q3-Q1), which explains about the
      dispersion of measured and calculated dose rate were also evaluated and found to
      be 10 and 16 microSv/y, respectively. The linear association between the order of
      ranks of the two dose rates was established by using Spearman's (rho) rank
      correlation that showed a coefficient of R = +0.90 with the intercept +1.9,
      whereas Pearson's correlation was observed with a coefficient of R = +0.93 with
      the intercept -25.6. Wilcoxon/Mann-Whitney test shows that, medians of the
      calculated and the measured dose rate as significantly different under the
      assumption of null hypothesis and measured dose rate was made to the normal
      distribution by applying Z-statistics. Value of chi(2) was calculated and found
      to be 284.95, which was very much greater than the critical value of chi(2)(0.05)
      = 43.77 at a degree of freedom 30, concluding that there is a highly significant
      difference between the measured and calculated dose rate at 5% significance
      level.

PMID- 17545659
TI  - Development of a neutron personal dose equivalent detector.
AB  - A new neutron-measuring instrument that is intended to measure a neutron personal
      dose equivalent, H(p)(10) was developed. This instrument is composed of two
      parts: (1) a conventional moderator-based neutron dose equivalent meter and (2) a
      neutron shield made of borated polyethylene, which covers a backward hemisphere
      to adjust the angular dependence. The whole design was determined on the basis of
      MCNP calculations so as to have response characteristics that would generally
      match both the energy and angular dependencies of H(p)(10). This new instrument
      will be a great help in assessing the reference values of neutron H(p)(10) during
      field testing of personal neutron dosemeters in workplaces and also in
      interpreting their readings.

PMID- 17545660
TI  - Plutonium in the Ozyorsk population.
AB  - Results of the long-term autopsy studies on plutonium body burden in the
      population of Ozyorsk situated in the vicinity of the radiochemical plant of the
      Mayak Production Association (Russia) have been presented. The data were obtained
      from radiochemical analysis of the soft tissue and bone samples collected at the
      autopsy of 239 non-occupational individuals for the period 1975-2003. The
      dynamics of plutonium accumulation in the Ozyorsk population is associated with
      the environmental contamination due to radioactive releases from the Mayak
      Production Association. Plutonium body burden and its distribution between the
      respiratory tract and extrapulmonary organs depend on the residence time of
      individuals in the city. Since the early 1950s, plutonium body burden in the
      Ozyorsk population was linearly increasing at the almost constant rate of
      accumulation and amounted to 5.8 Bq at 35 y after the beginning of residence in
      the city that was several tens of times higher than background levels of fallout
      plutonium. Distribution of plutonium in the body was also studied in Ozyorsk
      population. Plutonium deposition fraction in the respiratory tract did not exceed
      11% of the body burden in individuals with short residence times (1-9 y) and is
      halved for increasing residence times more than 10 y. The average skeleton:liver
      ratio was 65:20 = 3.25.

PMID- 17545661
TI  - TIARA: treatment initiatives after radiological accidents.
AB  - This paper describes the objectives, and reviews the progress, of the European
      project 'Treatment Initiatives After Radiological Accidents' (TIARA). TIARA forms
      part of the 'Preparatory Action for Security Research' (PASR) launched by the
      European Commission in 2004. The Preparatory Action is intended to reach
      preliminary conclusions on the needs for the security of EU citizens. It prepared
      a comprehensive Security Research Programme as part of the Commission's Seventh
      Framework Programme proposal, which was adopted in 2006 and launched in 2007. The
      principal purpose of TIARA is to constitute a European network that will
      participate in facilitating the management of a crisis in the event of the
      malevolent dispersal of radionuclides into the public environment.

PMID- 17545662
TI  - Comparisons of 239Pu inhalation doses calculated with ICRP 67 and proposed
      systemic models.
AB  - The International Commission on Radiological Protection (ICRP) has issued an age
      specific systemic biokinetic model for plutonium (Pu), which was later modified
      to give better agreement with measured urinary excretion data. Recently, the
      current ICRP systemic Pu model was improved by Leggett et al. based on recently
      developed data. Incorporation of 239Pu in the human body may result in
      significant internal radiation exposure. In the present work, the retentions in
      organs and tissues, the equivalent dose and effective dose from 239Pu for workers
      and members of the public were estimated and compared under the current ICRP and
      the proposed models. 239Pu contents in liver and in other soft tissue calculated
      with the proposed model are higher than predicted by the ICRP model, whereas bone
      content is lower than predicted by the ICRP model. Based on the proposed model,
      the inhalation equivalent dose coefficient in some organs, e.g. liver and
      kidneys, is increased, but there is no significant change in the effective
      inhalation dose coefficients of 239Pu for workers and members of the public.

PMID- 17545663
TI  - Voxel-based models representing the male and female ICRP reference adult--the
      skeleton.
AB  - For the forthcoming update of organ dose conversion coefficients, the
      International Commission on Radiological Protection (ICRP) will use voxel-based
      computational phantoms due to their improved anatomical realism compared with the
      class of mathematical or stylized phantoms used previously. According to the ICRP
      philosophy, these phantoms should be representative of the male and female
      reference adults with respect to their external dimensions, their organ topology
      and their organ masses. To meet these requirements, reference models of an adult
      male and adult female have been constructed at the GSF, based on existing voxel
      models segmented from tomographic images of two individuals whose body height and
      weight closely resemble the ICRP Publication 89 reference values. The skeleton is
      a highly complex structure of the body, composed of cortical bone, trabecular
      bone, red and yellow bone marrow and endosteum ('bone surfaces' in their older
      terminology). The skeleton of the reference phantoms consists of 19 individually
      segmented bones and bone groups. Sub-division of these bones into the above
      mentioned constituents would be necessary in order to allow a direct calculation
      of dose to red bone marrow and endosteum. However, the dimensions of the
      trabeculae, the cavities containing bone marrow and the endosteum layer lining
      these cavities are clearly smaller than the resolution of a normal CT scan and,
      thus, these volumes could not be segmented in the tomographic images. As an
      attempt to represent the gross spatial distribution of these regions as
      realistically as possible at the given voxel resolution, 48 individual organ
      identification numbers were assigned to various parts of the skeleton: every
      segmented bone was subdivided into an outer shell of cortical bone and a
      spongious core; in the shafts of the long bones, a medullary cavity was
      additionally segmented. Using the data from ICRP Publication 89 on elemental
      tissue composition, from ICRU Report 46 on material mass densities, and from ICRP
      Publication 70 on the distribution of the red bone marrow among and marrow
      cellularity in individual bones, individual elemental compositions for these
      segmented bone regions were derived. Thus, most of the relevant source and target
      regions of the skeleton were provided. Dose calculations using these regions will
      be based on fluence-to-dose response functions that are multiplied with the
      particle fluence inside specific bone regions to give the dose quantities of
      interest to the target tissues.

PMID- 17545664
TI  - Radiobiological investigations of soft X-rays near carbon, nitrogen, oxygen K
      shell edges on Aspergillus oryzae spores.
AB  - Soft X-rays at carbon, nitrogen, oxygen K-shell edges have special
      radiobiological effects. Using Aspergillus oryzae spores as sample, the radiation
      effects of soft X-rays near the K-shell edges of C, N and O elements from
      synchrotron radiation were investigated. Also the dose depositions of different X
      ray energies in spore were discussed. At the same time, the spores were
      irradiated by gamma rays from 60Co and relative biological effects were compared
      with those produced by soft X-rays. The results showed that soft X-rays near K
      shell edges of O element had higher ability of radiation damage than that of X
      rays near K-shell edges of C and N elements as compared with one another. But
      they all had higher killing abilities per unit dose than that of gamma rays from
      60Co. The relative biological effects (RBEs), the comparison of dose to gamma
      rays at 10% survival level, of the three soft X-rays were 1.65, 1.73 and 1.91,
      respectively.

PMID- 17545665
TI  - Proton-induced frequency distributions of ionization cluster size in propane.
AB  - The frequency distribution of clustered ionizations produced by a proton beam was
      measured in a nanodosimetric volume of the size of a DNA segment by means of an
      ion-counting nanodosimeter in the energy range from 0.4 to 3.5 MeV. In order to
      meet the needs of the ion-counting nanodosimeter, the accelerator's primary beam
      was reduced in intensity by means of Rutherford scattering. The comparison
      between experimental results and Monte Carlo simulations show a good agreement in
      the energy dependence of the mean cluster size, while the experimental cluster
      size distributions show a higher amount of large ionization clusters compared
      with those obtained with the simulations.

PMID- 17545666
TI  - Dose from slow negative muons.
AB  - Conversion coefficients from fluence to ambient dose equivalent, from fluence to
      maximum dose equivalent and quality factors for slow negative muons are examined
      in detail. Negative muons, when stopped, produce energetic photons, electrons and
      a variety of high-LET particles. Contribution from each particle type to the dose
      equivalent is calculated. The results show that for the high-LET particles the
      details of energy spectra and decay yields are important for accurate dose
      estimates. For slow negative muons the ambient dose equivalent does not always
      yield a conservative estimate for the protection quantities. Especially, the skin
      equivalent dose is strongly underestimated if the radiation-weighting factor of
      unity for slow muons is used. Comparisons to earlier studies are presented.

PMID- 17545667
TI  - The different intermolecular interactions of the soluble copper-binding domains
      of the menkes protein, ATP7A.
AB  - ATP7A is a P-type ATPase involved in copper(I) homeostasis in humans. It
      possesses a long N-terminal cytosolic tail containing six domains that are
      individually folded and capable of binding one copper(I) ion each. We
      investigated the entire N-terminal tail (MNK1-6) in solution by NMR spectroscopy
      and addressed its interaction with copper(I) and with copper(I)-HAH1, the
      physiological partner of ATP7A. At copper(I)-HAH1:MNK1-6 ratios of up to 3:1,
      thus encompassing the range of protein ratios in vivo, both the first and fourth
      domain of the tail formed a metal-mediated adduct with HAH1 whereas the sixth
      domain was simultaneously able to partly remove copper(I) from HAH1. These
      processes are not dependent on one another. In particular, formation of the
      adducts is not necessary for copper(I) transfer from HAH1 to the sixth domain.
      The present data, together with available in vivo studies, suggest that the
      localization of ATP7A between the trans-Golgi network and the plasma membrane may
      be regulated by the accumulation of the adducts with HAH1, whereas the main role
      of domains 5 and 6 is to assist copper(I) translocation.

PMID- 17545668
TI  - Recognition mechanism of galectin-4 for cholesterol 3-sulfate.
AB  - Galectin-4 binds to glycosphingolipids carrying 3-O-sulfated Gal residues, and it
      co-localizes on the cell surface of human colonic adenocarcinoma cells with
      glycosphingolipids carrying SO(-)(3)-->3Galbeta1-->3(GalNAc) residues (Ideo, H.,
      Seko, A., and Yamashita, K. (2005) J. Biol. Chem. 280, 4730-4737). In the present
      study, it was found that galectin-4 also binds to cholesterol 3-sulfate, which
      has no beta-galactoside moiety. This characteristic of galectin-4 is unique
      within the galectin family. The site-directed mutated galectin-4-R45A had
      diminished binding ability toward cholesterol 3-sulfate, suggesting that Arg(45)
      of galectin-4 is indispensable for cholesterol 3-sulfate recognition. Gel
      filtration and chemical cross-linking experiments revealed that some galectin-4
      exists as dimers, and this multivalency seemed to enhance its avidity for
      cholesterol 3-sulfate binding. Cholesterol 3-sulfate and sulfatide co-existed
      with galectin-4 in detergent-insoluble fractions of porcine esophagus and
      intestine, respectively. These results suggested that not only sulfated
      glycosphingolipids but also cholesterol 3-sulfate are endogenous ligands for
      galectin-4 in vivo.

PMID- 17545669
TI  - Activation of inhibitors by sortase triggers irreversible modification of the
      active site.
AB  - Sortases anchor surface proteins to the cell wall of Gram-positive pathogens
      through recognition of specific motif sequences. Loss of sortase leads to large
      reductions in virulence, which identifies sortase as a target for the development
      of antibacterials. By screening 135,625 small molecules for inhibition, we report
      here that aryl (beta-amino)ethyl ketones inhibit sortase enzymes from
      staphylococci and bacilli. Inhibition of sortases occurs through an irreversible,
      covalent modification of their active site cysteine. Sortases specifically
      activate this class of molecules via beta-elimination, generating a reactive
      olefin intermediate that covalently modifies the cysteine thiol. Analysis of the
      three-dimensional structure of Bacillus anthracis sortase B with and without
      inhibitor provides insights into the mechanism of inhibition and reveals binding
      pockets that can be exploited for drug discovery.

PMID- 17545670
TI  - Assessing the role of the active-site cysteine ligand in the superoxide reductase
      from Desulfoarculus baarsii.
AB  - Superoxide reductase is a novel class of non-heme iron proteins that catalyzes
      the one-electron reduction of O(2)(.) to H(2)O(2), providing an antioxidant
      defense in some bacteria. Its active site consists of an unusual non-heme Fe(2+)
      center in a [His(4) Cys(1)] square pyramidal pentacoordination. In this class of
      enzyme, the cysteine axial ligand has been hypothesized to be an essential
      feature in the reactivity of the enzyme. Previous Fourier transform infrared
      spectroscopy studies on the enzyme from Desulfoarculus baarsii revealed that a
      protonated carboxylate group, proposed to be the side chain of Glu(114), is in
      interaction with the cysteine ligand. In this work, using pulse radiolysis,
      Fourier transform infrared, and resonance Raman spectroscopies, we have
      investigated to what extent the presence of this Glu(114) carboxylic lateral
      chain affects the strength of the S-Fe bond and the reaction of the iron active
      site with superoxide. The E114A mutant shows significantly modified pulse
      radiolysis kinetics for the protonation process of the first reaction
      intermediate. Resonance Raman spectroscopy demonstrates that the E114A mutation
      results in both a strengthening of the S-Fe bond and an increase in the extent of
      freeze-trapping of a Fe-peroxo species after treatment with H(2)O(2) by a
      specific strengthening of the Fe-O bond. A fine tuning of the strength of the S
      Fe bond by the presence of Glu(114) appears to be an essential factor for both
      the strength of the Fe-O bond and the pK(a) value of the Fe(3+)-peroxo
      intermediate species to form the reaction product H(2)O(2).

PMID- 17545671
TI  - Cytosolic aspartate aminotransferase, a new partner in adipocyte
      glyceroneogenesis and an atypical target of thiazolidinedione.
AB  - We show that cytosolic aspartate aminotransferase (cAspAT) is involved in
      adipocyte glyceroneogenesis, a regulated pathway that controls fatty acid
      homeostasis by promoting glycerol 3-phosphate formation for fatty acid re
      esterification during fasting. cAspAT activity, as well as the incorporation of
      [(14)C]aspartate into the neutral lipid fraction of 3T3-F442A adipocytes was
      stimulated by the thiazolidinedione (TZD) rosiglitazone. Conversely, the ratio of
      fatty acid to glycerol released into the medium decreased. Regulation of cAspAT
      gene expression was specific to differentiated adipocytes and did not require any
      peroxisome proliferator-activated receptor gamma (PPARgamma)/retinoid X receptor
      alpha direct binding. Nevertheless, PPARgamma is indirectly necessary for both
      cAspAT basal expression and TZD responsiveness because they are, respectively,
      diminished and abolished by ectopic overexpression of a dominant negative
      PPARgamma. The cAspAT TZD-responsive site was restricted to a single AGGACA
      hexanucleotide located at -381 to -376 bp whose mutation impaired the specific
      RORalpha binding. RORalpha ectopic expression activated the cAspAT gene
      transcription in absence of rosiglitazone, and its protein amount in nuclear
      extracts is 1.8-fold increased by rosiglitazone treatment of adipocytes. Finally,
      the amounts of RORalpha and cAspAT mRNAs were similarly increased by TZD
      treatment of human adipose tissue explants, confirming coordinated regulation.
      Our data identify cAspAT as a new member of glyceroneogenesis, transcriptionally
      regulated by TZD via the control of RORalpha expression by PPARgamma in
      adipocytes.

PMID- 17545672
TI  - Monitoring patients using control charts: a systematic review.
AB  - OBJECTIVE: To systematically review the uses control charts to monitor clinical
      variables in individual patients. DATA SOURCES: Systematic searches of MEDLINE,
      CINAHL, Embase and five other databases yielded 74 studies, of which seven met
      our inclusion criteria of using control charts to monitor clinical variables for
      disease at an individual patient level. REVIEW METHODS: Included articles were
      reviewed independently by two reviewers. Data were extracted on study design
      clinical condition or disease being monitored, clinical variable or marker,
      measurement method, outcome measure and any changes in clinical indicator
      identified in the articles. RESULTS: Control charts were applied to four
      conditions--hypertension, asthma, renal function post-transplant and diabetes.
      Studies fell into two categories. Three studies sought to determine the
      'performance' of control charts in comparison with existing 'gold standard
      methods' in terms of sensitivity and specificity based on moderate sample sizes
      (n = 35-45). This category of studies found control charts to be simple, low
      cost, effective tools with good sensitivity and specificity characteristics and
      concluded in favour of control charts. The other four studies were individual
      patient case-studies in which the use of control charts to monitor clinical
      variables was associated with a positive impact on patient and carer experience
      albeit anecdotally and with varying degrees of attention. CONCLUSIONS: Control
      charts appear to have a promising but largely under-researched role in monitoring
      clinical variables in individual patients. Furthermore, rigorous evaluation of
      control charts is required.

PMID- 17545673
TI  - Questionnaire to assess patient satisfaction with pharmaceutical care in Spanish
      language.
AB  - OBJECTIVE: To develop and validate a questionnaire, in Spanish, for assessing
      patient satisfaction with pharmaceutical care received in community pharmacies.
      DESIGN: Selection and translation of questionnaire's items; definition of
      response scale and demographic questions. Evaluation of face and content
      validity, feasibility, factor structure, reliability and construct validity.
      SETTING: Forty-one community pharmacies of the province of Santa Fe. Argentina.
      PARTICIPANTS: Questionnaire administered to patients receiving pharmaceutical
      care or traditional pharmacy services. MAIN OUTCOME MEASURE: Pilot test to assess
      feasibility. Factor analysis used principal components and varimax rotation.
      Reliability established using internal consistency with Cronbach's alpha.
      Construct validity determined with extreme group method. RESULTS: A self
      administered questionnaire with 27 items, 5-point Likert response scale and
      demographic questions was designed considering multidimensional structure of
      patient satisfaction. Questionnaire evaluates cumulative experience of patients
      with comprehensive pharmaceutical care practice in community pharmacies. Two
      hundred and seventy-four complete questionnaires were obtained. Factor analysis
      resulted in three factors: Managing therapy, Interpersonal relationship and
      General satisfaction, with a cumulative variance of 62.51%. Cronbach's alpha for
      the whole questionnaire was 0.96, and 0.95, 0.88 and 0.76 for the three factors,
      respectively. Mann-Whitney test for construct validity did not showed significant
      differences between pharmacies that provide pharmaceutical care and those that do
      not, however, 23 items showed significant differences between the two groups of
      pharmacies. CONCLUSION: The questionnaire developed can be a reliable and valid
      instrument to assess patient satisfaction with pharmaceutical care in community
      pharmacies in Spanish. Further research is needed to deepen the validation
      process.

PMID- 17545674
TI  - High membrane transport status on peritoneal dialysis is not associated with
      reduced survival following transfer to haemodialysis.
AB  - BACKGROUND: High transporter status is associated with reduced survival of
      patients receiving peritoneal dialysis (PD). This may be due primarily to the
      development of complications related to the PD process, in which case the
      survival disadvantage may not persist following transfer to haemodialysis (HD).
      In this study, we aimed to assess the impact of peritoneal membrane transporter
      status on patient survival and the likelihood of return to PD following transfer
      from PD to HD. METHODS: The Australia and New Zealand Dialysis and Transplant
      (ANZDATA) Registry was searched to identify all patients between 1 April 1999 and
      31 March 2004 who had received PD and subsequently transferred to HD, in whom an
      incident 4 h dialysate: plasma creatinine ratio was recorded. A Cox proportional
      hazards model was used to identify factors significantly associated with patient
      and technique survival after commencement of HD. RESULTS: A total of 918 patients
      were included in the analysis. On multivariate Cox regression analysis there was
      no difference in survival between transport groups relative to the reference
      group of low average transporters (adjusted hazard ratio (HR) 0.71, 95% CI 0.42
      1.19, P = 0.19, HR 0.94, 95% CI 0.63-1.38, P = 0.73 and HR 0.24, 95% CI 0.06
      1.01, P = 0.051 for high, high average and low transporter groups, respectively).
      Significant predictors of mortality were duration of PD more than 22 months (HR
      2.32, 95% CI 1.24-4.33, P = 0.01), increasing age, late referral to a
      nephrologist and a history of diabetes mellitus. The likelihood of returning to
      PD was increased if initial PD technique failure was due to mechanical
      complications compared with all other causes of failure [HR 3.65 (95% CI 2.78
      4.79) P < 0.001] and decreased with higher body mass index [HR 0.97 per kg/m(2)
      (95% CI 0.94-0.99), P = 0.01] and the 4 h dialysate: plasma creatinine ratio
      considered as a continuous variable [4 h D:P Cr; HR 0.32 per unit (95% CI 0.12
      0.89), P = 0.03]. CONCLUSIONS: The survival disadvantage associated with high
      peritoneal membrane transport status during PD treatment does not persist
      following transfer to HD. Early transfer to HD may be beneficial in this patient
      group.

PMID- 17545675
TI  - Inhibitory effects of matrix metalloproteinase inhibitor ONO-4817 on
      morphological alterations in chlorhexidine gluconate-induced peritoneal sclerosis
      rats.
AB  - BACKGROUND: The activity of gelatinase, matrix metalloproteinase-2, in effluent
      was increased in peritoneal dialysis patients with encapsulated peritoneal
      sclerosis (EPS) and in chlorhexidine gluconate-induced peritoneal sclerosing (PS)
      animal models. The objective of the present study was to investigate the effect
      of matrix metalloproteinase inhibitor (ONO-4817), an anticancer agent with anti
      angiogenesis and anti-infiltration effects, on the development of peritoneal
      fibrosis in chlorhexidine gluconate-induced PS rats. METHODS: Forty-five Sprague
      Dawley (S-D) rats were intraperitoneally injected with saline as control (n = 15)
      or with chlorhexidine gluconate (CH) (1.5 ml/100 g) in the CH group (n = 15). ONO
      4817 (5 mg/rat) was administered intravenously to CH rats (the ONO-4817 group, n
      = 15) from initiation to the end of the study. After 22 days of ONO-4817
      administration, the rats were sacrificed and the parietal peritoneum was
      harvested. The gene expressions of transforming growth factor-beta (TGF-beta),
      alpha-smooth muscle actin (alpha-SMA) and type I collagen in the peritoneum were
      analysed by the reverse transcription-polymerase chain reaction (RT-PCR).
      Peritoneal tissues were also evaluated immunohistologically. RESULTS: ONO-4817
      significantly inhibited thickening of the submesothelial layer and accumulation
      of type I collagen in the peritoneum. ONO-4817 also prevented increases of the
      number of macrophages and blood vessels. The expressions of TGF-beta, alpha-SMA
      and type I collagen in the peritoneum were markedly suppressed in ONO-4817
      treated rats. CONCLUSION: It appears that the administration of the MMP inhibitor
      ONO-4817 might be a new approach to the amelioration of PS.

PMID- 17545676
TI  - Transient allograft dysfunction from immune reconstitution in a patient with
      polyoma BK-virus-associated nephropathy.

PMID- 17545677
TI  - Parathyroid hormone stimulates the endothelial nitric oxide synthase through
      protein kinase A and C pathways.
AB  - BACKGROUND: Parathyroid hormone (PTH), the major systemic calcium regulating
      hormone has been implicated in the development of hypertension and the occurrence
      of uraemic vascular changes. As nitric oxide synthase (NOS) is involved in the
      production of nitric oxide, and acute PTH effect is characterized by
      vasodilation, the effect of PTH on the endothelial NOS (eNOS) system was measured
      in cultured human umbilical cord vein endothelial cells (HUVEC) and the pathways
      possibly involved were studied. METHODS: The presence of the PTH receptor-1
      (PTHR1) on the HUVEC membrane was examined by RT-PCR, immunocytochemistry and
      western blot. HUVEC were stimulated with 10(-12) to 10(-10) mol/l PTH. The eNOS
      mRNA expression was established by RT-PCR and the eNOS protein levels were
      determined by western blot. The eNOS activity was measured by the conversion of
      [(14)C]arginine to [(14)C]citrulline. RESULTS: PTHR1 has been found to be
      expressed in HUVEC and its expression is depressed by increasing concentrations
      of PTH. PTH induced a significant increase in eNOS mRNA (10(-11) mol/l: 1.87 +/-
      0.16, P = 0.012; 10(-10) mol/l: 1.96 +/- 0.28, P = 0.007, fold of control), and
      protein expression. The eNOS activity was also significantly stimulated (10(-11)
      mol/l: 1139 +/- 203; 10(-10) mol/l: 1323 +/- 216 vs control: 621 +/- 154 cpm/150
      mug protein, P < 0.01). The addition of calphostin C (PKC inhibitor) or Rp-cAMP
      (PKA inhibitor) reduced the eNOS mRNA, protein expression and activity of PTH
      stimulated HUVEC. The combined treatment of calphostin C and Rp-cAMP abolished
      the eNOS protein expression and activity. CONCLUSION: PTH induces an increased
      activity of the eNOS system; probably both PKA and PKC pathways are involved in
      this activation. Such data may explain the vasodilation observed after acute
      treatment with PTH.

PMID- 17545678
TI  - Bosentan and losartan ameliorate acute renal failure associated with mild but not
      strong NO blockade.
AB  - BACKGROUND: Acute renal failure (ARF) is a devastating illness, especially when
      it occurs in various conditions with impaired nitric oxide (NO) synthesis, such
      as arterial hypertension, heart failure and some renal diseases. We have directed
      our investigations to effects of both angiotensin II (AII) and endothelin (ET)
      receptor blockade associated with mild or strong NO deficiency on haemodynamic,
      biochemical and morphological parameters in experimental post-ischaemic ARF.
      METHODS: In this study, we used bosentan (dual, ETA/ETB-receptor antagonist),
      losartan (non-peptide, competitive antagonist of type I AII receptor), and NG
      nitro-L-arginine methyl ester (L-NAME), inhibitor of NO synthesis. Experiments
      were performed in anaesthetized, adult male Wistar rats. The right kidney was
      removed and the renal ischaemia was performed by clamping the left renal artery
      for 45 min. Experimental groups received receptor antagonists (bosentan or
      losartan) or vehicle (saline) in the femoral vein 20 min before, during and 20
      min after the period of ischaemia. L-NAME was given as i.v. bolus before each
      antagonist infusion. All parameters were measured 24 h after reperfusion.
      RESULTS: Our results showed that strong NO blockade overcame effects of both ET
      and AII receptor blockade in experimental post-ischaemic ARF. In addition, the
      AII receptor blockade had a harmful effect on this condition, probably due to
      disturbed autoregulatory renal function. On the other hand, ET and AII receptor
      blockade in mild NO blockade associated with reperfusion injury, improves the
      most haemodynamic, biochemical and morphological parameters. CONCLUSIONS: We
      concluded that experimental post-ischaemic ARF is neither AII nor ET mediated in
      case of strong NO blockade, but, in more realistic conditions of mild NO
      deficiency, these peptides represent significant players whose receptor blockade
      expressed relevant therapeutic potential.

PMID- 17545679
TI  - Demonstration of secretory IgA in kidneys of patients with IgA nephropathy.
AB  - BACKGROUND: Recently we reported a possible role for secretory IgA (SIgA) in IgA
      nephropathy (IgAN), as suggested by increased serum levels in patients with
      active disease and accumulation of SIgA in a glomerular eluate. Therefore, we
      attempted to find support for these findings by analysis of the presence of SIgA
      in biopsies of IgAN patients. METHODS: Renal biopsies of 26 patients with biopsy
      proven IgAN were analysed for the presence of SIgA and complement proteins.
      RESULTS: In 15% mesangial deposition of SIgA was demonstrated, using a specific
      staining for secretory component (SC) and colocalization with IgA. The presence
      of SIgA in these biopsies showed a strong correlation with deposition of mannose
      binding lectin (MBL) and C4d. Moreover, we observed a strong colocalization
      between SIgA and MBL or C4d. This local complement activation has previously been
      linked to more severe renal disease. CONCLUSIONS: Therefore, these data provide
      additional evidence for a pathogenic role for SIgA in IgA nephropathy.

PMID- 17545680
TI  - Effective treatment of four consecutive idiopathic membranous nephropathy
      patients.

PMID- 17545681
TI  - Glutamine regulates the human epithelial intestinal HCT-8 cell proteome under
      apoptotic conditions.
AB  - Glutamine plays a key role in the metabolism of rapidly dividing cells, including
      enterocytes and lymphocytes, which may contribute to its beneficial clinical
      effects. Gut mucosal homeostasis is achieved through a balance between cell
      proliferation and apoptosis. In T cells, glutamine up-regulates antiapoptotic
      proteins and down-regulates proapoptotic proteins. In gut mucosa, glutamine
      prevents apoptosis in rat epithelial cell lines, whereas glutamine starvation
      induces apoptosis through caspase activation. Finally glutamine specifically
      prevents tumor necrosis factor-alpha-related apoptosis in the human intestinal
      cell line HT-29. Comparative functional proteomics enables the characterization
      of each differentially expressed protein in intestinal cells in response to
      modifications of nutritional environment. The influence of glutamine on
      intestinal proteome expression in apoptotic conditions has not been studied and
      evaluated. This comparative proteomics study was performed in the human
      epithelial intestinal cell line HCT-8 under experimental apoptotic conditions to
      investigate the influence of glutamine on protein expression during apoptosis.
      The pharmaconutritional effects of glutamine were determined under 2 mm
      (physiological concentration) and 10 mm (pharmaconutritional concentration)
      conditions. About 1,800 protein spots were revealed in both conditions.
      Comparative assessments indicated that 28 proteins were differentially expressed
      significantly (i.e. at least 2-fold modulated and Student's t test with p </=
      0.05) in response to an increase of glutamine concentration in the culture
      medium. Twenty-four proteins were identified by mass spectrometry and associated
      databases. From these proteins, 34% are involved in cell cycle and apoptosis
      mechanisms, 17% are involved in signal transduction, and 13% are involved in
      cytoskeleton organization. These data were integrated in a proposed schema of the
      interactome under apoptotic conditions. In conclusion, this study provides the
      first holistic picture of proteome modulation by glutamine in a human enterocytic
      cell line under apoptotic conditions and supports further evaluation of
      nutritional modulation of human intestinal proteome in various pathological
      conditions where apoptosis may be involved.

PMID- 17545682
TI  - Shotgun identification of the structural proteome of shrimp white spot syndrome
      virus and iTRAQ differentiation of envelope and nucleocapsid subproteomes.
AB  - White spot syndrome virus (WSSV) is a major pathogen that causes severe mortality
      and economic losses to shrimp cultivation worldwide. The genome of WSSV contains
      a 305-kb double-stranded circular DNA, which encodes 181 predicted ORFs. Previous
      gel-based proteomics studies on WSSV have identified 38 structural proteins. In
      this study, we applied shotgun proteomics using off-line coupling of an LC system
      with MALDI-TOF/TOF MS/MS as a complementary and comprehensive approach to
      investigate the WSSV proteome. This approach led to the identification of 45
      viral proteins; 13 of them are reported for the first time. Seven viral proteins
      were found to have acetylated N termini. RT-PCR confirmed the mRNA expression of
      these 13 newly identified viral proteins. Furthermore iTRAQ (isobaric tags for
      relative and absolute quantification), a quantitative proteomics strategy, was
      used to distinguish envelope proteins and nucleocapsid proteins of WSSV. Based on
      iTRAQ ratios, we successfully identified 23 envelope proteins and six
      nucleocapsid proteins. Our results validated 15 structural proteins with
      previously known localization in the virion. Furthermore the localization of an
      additional 12 envelope proteins and two nucleocapsid proteins was determined. We
      demonstrated that iTRAQ is an effective approach for high throughput viral
      protein localization determination. Altogether WSSV is assembled by at least 58
      structural proteins, including 13 proteins newly identified by shotgun proteomics
      and one identified by iTRAQ. The localization of 42 structural proteins was
      determined; 33 are envelope proteins, and nine are nucleocapsid proteins. A
      comprehensive identification of WSSV structural proteins and their localization
      should facilitate the studies of its assembly and mechanism of infection.

PMID- 17545683
TI  - Necrotizing fasciitis and hypothyroidism.

PMID- 17545684
TI  - Cost effectiveness of adalimumab for the treatment of ankylosing spondylitis in
      the United Kingdom.
AB  - OBJECTIVES: This study evaluated the cost effectiveness of adalimumab vs
      conventional therapy in patients with active ankylosing spondylitis (AS).
      METHODS: The analysis was based on pooled data from two Phase III studies of
      adalimumab in active AS. Patients with an inadequate response to >/=1 NSAID
      received adalimumab 40 mg every other week (n = 246) or placebo (n = 151) for 24
      weeks. A microsimulation model was developed with patients being treated with
      adalimumab according to the International ASAS Consensus Statement and BSR
      guidelines. The pooled adalimumab data, as well as data from the Outcome
      Assessment in AS International Study (OASIS) database and the literature, were
      used to model patients' BASDAI and BASFI scores and costs and health-related
      quality of life associated with various degrees of disease activity. Costs (in
      2004 British pound) of AS, drug, administration, monitoring, hospitalization and
      AEs were calculated from the perspective of the UK NHS. Discounting was applied
      at 3.5% per year for costs and benefits as per the NICE reference case for
      economic evaluations. Uncertainty was addressed via sensitivity analyses.
      RESULTS: The incremental cost-effectiveness ratio (ICER) of adalimumab vs
      conventional therapy was estimated to improve with longer time horizons (48 weeks
      to 5 and 30 yrs). The central estimate was that, over 30 yrs, adalimumab therapy
      yielded 1.03 more quality-adjusted life-years (QALYs) per patient initiating
      therapy. Some AS treatment-related costs were estimated to be offset by
      adalimumab (at 10,750 pounds/patient), leaving a total incremental cost
      (adalimumab vs conventional therapy) at 23,857 pounds per patient. The 30-yr ICER
      of adalimumab vs conventional therapy was estimated at 23 pounds 097/QALY.
      Sensitivity analyses demonstrated robustness of results. When indirect costs were
      also included (analysis from societal perspective), ICER improved to 5093
      pounds/QALY. CONCLUSIONS: This analysis indicates that adalimumab, when used
      according to UK treatment guidelines, is cost-effective vs conventional therapy
      for treating AS patients.

PMID- 17545685
TI  - Human MD-2 discrimination of meningococcal lipid A structures and activation of
      TLR4.
AB  - MD-2, a eukaryotic accessory protein, is an essential component for the molecular
      pattern recognition of bacterial endotoxins. MD-2 interacts with lipid A of
      endotoxins [lipopolysaccharide (LPS) or lipooligosaccharide (LOS)] to activate
      human toll-like receptor (TLR) 4. The structure of lipid A influences the
      subsequent activation of human TLR4 and the immune response, but the basis for
      the discrimination of lipid A structures is unclear. A recombinant human MD-2
      (rMD-2) protein was produced in the Pichia pastoris yeast expression system.
      Human embryonic kidney (HEK293) cells were transfected with human TLR4 and were
      stimulated with highly purified LOS (0.56 pmol) from Neisseria meningitidis or
      LPS from other structurally defined bacterial endotoxins in the presence or
      absence of human rMD-2. Human rMD-2 restored, in a dose-dependent manner,
      interleukin (IL-8) responsiveness to LOS or LPS in TLR4-transfected HEK293 cells.
      The interaction of endotoxin with human rMD-2 was then assessed by enzyme-linked
      immunosorbent assays. Wild-type meningococcal LOS (Wt m LOS) bound human rMD-2,
      and binding was inhibited by an anti-MD-2 antibody to MD-2 dose-dependently (P <
      0.005). Wt m LOS or meningococcal KDO(2)-lipid A had the highest binding affinity
      for human rMD-2; unglycosylated meningococcal lipid A produced by meningococci
      with defects in the 3-deoxy-d-manno-2-octulosonic acid (KDO) biosynthesis pathway
      did not appear to bind human rMD-2 (P < 0.005). The affinity of meningococcal LOS
      with a penta-acylated lipid A for human rMD-2 was significantly less than that
      for hexa-acylated LOS (P < 0.05). The hierarchy in the binding affinity of
      different lipid A structures for human rMD-2 was directly correlated with
      differences in TLR4 pathway activation and cytokine production by human
      macrophages.

PMID- 17545686
TI  - Drospirenone increases endothelial nitric oxide synthesis via a combined action
      on progesterone and mineralocorticoid receptors.
AB  - BACKGROUND: Progestins have actions on the cardiovascular system, which depend on
      the structure as well as on receptor binding characteristics. Drospirenone (DRSP)
      is a progestin that uniquely interferes with the signaling of the
      mineralocorticoid receptor (MR). Hormone therapy containing DRSP results in blood
      pressure reduction in hypertensive post-menopausal women. METHODS: We describe
      the effects of DRSP on endothelial nitric oxide (NO) synthesis and compare them
      with those of progesterone (P) and of medroxyprogesterone acetate (MPA). In
      addition, we herein tested the relevance of the anti-mineralocorticoid activity
      of DRSP for NO synthesis. RESULTS: DRSP results in rapid activation of the
      endothelial NO synthase (eNOS) through mitogen-activated protein kinases and
      phosphatidylinositol 3-kinase as well as in enhanced eNOS expression. These
      actions depend on P receptor. When the cells are exposed to aldosterone, a
      reduction of eNOS expression is found that is antagonized by DRSP. This action is
      not shared by P or MPA. In addition, DRSP does not interfere with the induction
      or activation of eNOS induced by estradiol, as opposed to MPA. CONCLUSIONS: DRSP
      acts on endothelial cells via a combined action through the P and MRs. These
      results help to interpret the anti-hypertensive effects of hormonal therapies
      containing DRSP.

PMID- 17545687
TI  - Highly specific and sensitive rise in Days 14-17 pro-alphaC inhibin with clinical
      pregnancy after frozen embryo transfer with ovulatory cycles.
AB  - BACKGROUND: Pro-alphaC inhibins are luteal derived analytes peaking in the
      maternal serum as early as Day 16 after conception. We set out to verify a
      previous post hoc analysis which suggested that pro-alphaC levels measured this
      early are extremely sensitive in predicting clinical pregnancy success after
      unstimulated IVF with ovulatory cycles. METHODS: Prospective observational study
      of 246 women undergoing frozen embryo transfer with ovulatory cycles. Serum pro
      alphaC and beta-HCG levels at 14-17 days after conception were measured by enzyme
      linked immunosorbent assay and grouped according to whether a clinical pregnancy
      occurred (demonstrable cardiac activity at > or =6 weeks' gestation). RESULTS: Of
      34 (13.8%) women who achieved a clinical pregnancy, median (25th-75th centile)
      Days 14-17 pro-alphaC levels were 995 pg/ml (758-1463), 6- to 7-fold higher than
      levels observed in the remainder who did not fall pregnant (112.8 pg/ml (104
      121); P < 0.0001). At a fixed 95% specificity, pro-alphaC was 100% sensitive in
      predicting clinical pregnancy. The best specificities achieved at 100%
      sensitivity were; 94.8% for pro-alphaC, 96.7% for beta-HCG and 98.1% when both
      analytes were combined. CONCLUSIONS: Clinical pregnancy is always associated with
      a release of luteal derived pro-alphaC 14-17 days after conception. Pro-alphaC
      may play a possible biological role and be a useful clinical biomarker of luteal
      health.

PMID- 17545688
TI  - Predictors of success and effect of biphasic energy on electrical cardioversion
      in patients with persistent atrial fibrillation.
AB  - AIMS: We sought predictors of successful electrical cardioversion (ECV) and the
      effect of biphasic energy in patients considered candidates for rhythm control.
      METHODS AND RESULTS: The patients were drawn from a registry, which included
      prospectively 1355 consecutive patients with persistent atrial fibrillation who
      underwent ECV in 96 Spanish hospitals. Successful ECV was considered excluding
      patients with an early relapse. Factors related to successful cardioversion were
      evaluated using logistic regression with the patients segregated with respect to
      the use of monophasic or biphasic energy. Sinus rhythm was restored in 92% of the
      patients, of which, 5% had an early relapse. Thus, we considered that a
      successful ECV was achieved in 87% of patients. Body surface area was the only
      factor independently related to failure of the monophasic energy cardioversion
      (OR = 0.20; P = 0.001). No single factor was predictive of biphasic energy
      cardioversion failure. Biphasic energy was more effective in restoring sinus
      rhythm in patients with body surface area >2.05 m(2) (83% success in monophasic
      vs. 92% in biphasic; P = 0.02). CONCLUSION: Body surface area was the only factor
      related to the success of ECV, but only in patients treated with monophasic
      energy. Biphasic energy should be the technique-of-choice in patients with a
      large body surface area.

PMID- 17545690
TI  - Founder and recurrent CDH1 mutations in families with hereditary diffuse gastric
      cancer.
AB  - CONTEXT: Hereditary diffuse gastric cancer is caused by germline mutations in the
      epithelial cadherin (CDH1) gene and is characterized by an increased risk for
      diffuse gastric cancer and lobular breast cancer. OBJECTIVE: To determine whether
      recurring germline CDH1 mutations occurred due to independent mutational events
      or common ancestry. DESIGN, SETTING, AND PATIENTS: Thirty-eight families
      diagnosed clinically with hereditary diffuse gastric cancer were accrued between
      November 2004 and January 2006 and were analyzed for CDH1 mutations as part of an
      ongoing study at the British Columbia Cancer Agency. Twenty-six families had at
      least 2 gastric cancer cases with 1 case of diffuse gastric cancer in a person
      younger than 50 years; 12 families had either a single case of diffuse gastric
      cancer diagnosed in a person younger than 35 years or multiple cases of diffuse
      gastric cancer diagnosed in persons older than 50 years. MAIN OUTCOME MEASURES:
      Classification of family members as carriers or noncarriers of CDH1 mutations.
      Haplotype analysis to assess recurring mutations for common ancestry was
      performed on 7 families from this study and 7 previously reported families with
      the same mutations. RESULTS: Thirteen mutations (6 novel) were identified in 15
      of the 38 families (40% detection rate). The 1137G>A splicing mutation and the
      1901C>T (A634V) missense/splicing mutation occurred on common haplotypes in 2
      families but on different haplotypes in a third family. The 2195G>A (R732Q)
      missense/splicing mutation occurred in 2 families on different haplotypes. The
      2064-2065delTG mutation occurred on a common haplotype in 2 families. Two
      families from this study plus 2 additional families carrying the novel 2398delC
      mutation shared a common haplotype, suggesting a founder effect. All 4 families
      originate from the southeast coast of Newfoundland. Due to concentrations of
      lobular breast cancer cases, 2 branches of this family had been diagnosed as
      having hereditary breast cancer and were tested for BRCA mutations. Within these
      4 families, the cumulative risk by age 75 years in mutation carriers for
      clinically detected gastric cancer was 40% (95% confidence interval [CI], 12%
      91%) for males and 63% (95% CI, 19%-99%) for females and the risk for breast
      cancer in female mutation carriers was 52% (95% CI, 29%-94%). CONCLUSIONS:
      Recurrent CDH1 mutations in families with hereditary diffuse gastric cancer are
      due to both independent mutational events and common ancestry. The presence of a
      founder mutation from Newfoundland is strongly supported.

PMID- 17545691
TI  - Clinical implications of founder and recurrent CDH1 mutations in hereditary
      diffuse gastric cancer.

PMID- 17545692
TI  - N-Glycosylation regulates endothelial lipase-mediated phospholipid hydrolysis in
      apoE- and apoA-I-containing high density lipoproteins.
AB  - Endothelial lipase (EL) is a member of the triglyceride lipase gene family with
      high phospholipase and low triacylglycerol lipase activities and a distinct
      preference for hydrolyzing phospholipids in HDL. EL has five potential N
      glycosylation sites, four of which are glycosylated. The aim of this study was to
      determine how glycosylation affects the phospholipase activity of EL in
      physiologically relevant substrates. Site-directed mutants of EL were generated
      by replacing asparagine (N) 62, 118, 375, and 473 with alanine (A). These glycan
      deficient mutants were used to investigate the kinetics of phospholipid
      hydrolysis in fully characterized preparations of spherical reconstituted high
      density lipoprotein (rHDL) containing apolipoprotein E2 (apoE2) [(E2)rHDL], apoE3
      [(E3)rHDL], apoE4 [(E4)rHDL], or apoA-I [(A-I)rHDL] as the sole apolipoprotein.
      Wild-type EL hydrolyzed the phospholipids in (A-I)rHDL, (E2)rHDL, (E3)rHDL, and
      (E4)rHDL to similar extents. The phospholipase activities of EL N118A, EL N375A,
      and EL N473A were significantly diminished relative to that of wild-type EL, with
      the greatest reduction being apparent for (E3)rHDL. The phospholipase activity of
      EL N62A was increased up to 6-fold relative to that of wild-type EL, with the
      greatest enhancement of activity being observed for (E2)rHDL. These data show
      that individual N-linked glycans have unique and important effects on the
      phospholipase activity and substrate specificity of EL.

PMID- 17545693
TI  - Impact of the universal hepatitis B immunization program in Mongolia:
      achievements and challenges.
AB  - BACKGROUND: The impact of the universal infant hepatitis B (HB) immunization
      program initiated in 1991 in Mongolia is still unclear. METHODS: A nationwide
      school-based cross-sectional serosurvey was conducted in 2004, with stratified,
      multistage, random cluster sampling from all public elementary schools (n=593) in
      Mongolia. All children were tested for serological markers of hepatitis B virus
      (HBV). RESULTS: Serology results were available for 1,145 children (592 boys and
      553 girls) aged 7-12 years (survey response rate: 93%). Immunization card was
      available for 702 (61.3%) children. The coverage of complete HB vaccination was
      60.1% and it was increased by birth cohort from 44% to 76%. Significantly higher
      proportion of children in Metropolitan cities (75.2%) was completely vaccinated
      with HB compared to those in Province centers (55.7%) and rural areas (59.1%).
      HBV infection occurred in 5.9%, 13.2%, and 20.8% of complete vaccinees living in
      Metropolitan, Province centers, and rural areas, respectively; of whom 1.2%,
      2.9%, and 8.6% were HB surface antigen (HBsAg) carriers, respectively. Only 17.0%
      of the children had protective anti-HBs which decreased from 31.1% to 16.3% among
      7 to 12-year-olds indicating its decay with time. CONCLUSIONS: Prevalence of HBV
      infection and carriage among young generation meaningfully declined compared with
      those of previous studies in Mongolia. The coverage of birth dose and complete HB
      vaccination was significantly low in Province centers and rural areas which
      should be taken into consideration.

PMID- 17545694
TI  - A case-control study in Hiroshima and Nagasaki examining non-radiation risk
      factors for thyroid cancer.
AB  - BACKGROUND: Because little is known about the etiology of thyroid cancer in
      Japan, we conducted a case-control study of thyroid cancer and lifestyle and
      other risk factors. The present report focuses on medical history, family
      history, smoking and alcohol drinking, and their interactions with radiation
      exposure. METHODS: Thyroid cancer cases reported to the Hiroshima and Nagasaki
      tumor registries during 1970-1986 were histologically reviewed by pathologists.
      For each of 362 cases with papillary or follicular adenocarcinoma diagnosed at
      <75 years of age, one control without cancer matched on city, sex, year of birth,
      and atomic-bomb radiation exposure was selected from the Life Span Study cohort
      or the offspring cohort. The cohort subjects were residents of Hiroshima and
      Nagasaki with or without atomic-bomb radiation exposure. Information on risk
      factors was obtained through a pre-structured interview carried out in 1986-1988.
      RESULTS: Analysis using conditional logistic regression showed history of goiter
      or thyroid nodule and family history of cancer to be significantly associated
      with an increased odds ratio for thyroid cancer. Smoking and alcohol drinking
      were significantly and independently associated with a reduced odds ratio.
      Interaction between smoking and alcohol drinking was not evident based on either
      an additive model or a multiplicative model. Radiation exposure did not
      significantly modify the associations between these factors and thyroid cancer
      risk. CONCLUSION: History of goiter/nodule and family history of cancer were risk
      factors for thyroid cancer. Smoking and alcohol drinking were independently
      associated with reduced risk. Self-reported retrospective information presents
      some limitations in interpretation of the data.

PMID- 17545695
TI  - Dietary intake of fatty acids and serum C-reactive protein in Japanese.
AB  - BACKGROUND: Inflammation has been established as a risk factor for cardiovascular
      diseases. The relationships of polyunsaturated fatty acids (PUFAs) and
      monounsaturated fatty acids to inflammation are still controversial in Western
      populations. The relationships are not clear in Japanese whose intake of seafood
      based long-chain n-3 PUFAs is high. METHODS: We conducted a cross-sectional
      epidemiologic study in the Japanese population (1,556 men and 1,461 women aged 35
      60). Serum high sensitivity C-reactive protein (CRP) was measured, and intakes of
      7 specific fatty acids (% of energy) were evaluated by a validated self
      administered dietary history questionnaire. RESULTS: CRP was significantly and
      inversely related to the intakes of oleic acid (p=0.008) and alpha-linolenic acid
      (p=0.026) in women after adjustment for confounding factors. A multiple
      regression analysis showed that, especially in the middle tertile of long-chain n
      3 PUFAs (eicosapentaenoic acid and docosahexaenoic acid) intake, CRP was
      inversely related to the intake of oleic acid and linoleic acid in both sexes and
      to the intake of alpha-linolenic acid in women. CONCLUSION: Intakes of oleic
      acid, linoleic acid, and alpha-linolenic acid would reduce serum CRP, especially
      when the intake of long-chain n-3 PUFAs is at a moderate level in Japanese.

PMID- 17545696
TI  - Different income information as an indicator for health inequality among Japanese
      adults.
AB  - BACKGROUND: There are several alternative indicators of income information, which
      is a fundamental measure of individual socioeconomic position. In this study, we
      compared the degrees of associations of four types of income information with
      health variables among Japanese adults. METHODS: Using a nationally
      representative sample of 29,446 men and 32,917 women aged 20 years and over, the
      associations between four income indicators and health variables were examined
      using the odds ratio in logistic regression analysis and the concentration index
      by sex and age group (20-59 years and 60+ years). Income indicators consisted of
      total household income, equivalent household income, total household expenditure,
      and equivalent household expenditure. Current smoking and self-rated health
      statuses were used as health variables. RESULTS: A low income was associated with
      a high prevalence of smoking and fair/poor self-rated health, with some
      differences among sex and age groups and income indicators, but less difference
      among methods of statistical analyses. Total and equivalent incomes were
      similarly and more markedly associated with smoking and self-rated health
      statuses, whereas equivalent expenditure showed the smallest degree of health
      difference. For the population aged 60+ years, the degree of health differences
      in smoking was similar between income and expenditure. CONCLUSIONS: Although the
      degree of income-related health differences is dependent on health outcome and
      both sex and age group, this study suggests that either crude or equivalent
      household income is a useful indicator for health inequality among Japanese
      adults.

PMID- 17545697
TI  - Reproducibility of a short food frequency questionnaire for Japanese general
      population.
AB  - BACKGROUND: In epidemiologic field studies, a food frequency questionnaire (FFQ)
      is one of the most feasible tools to assess usual dietary habits. The purpose of
      this study is to evaluate the reproducibility of consumption of foods and
      nutrients assessed with a self-administered short FFQ in a Japanese general
      population. METHODS: We have investigated 1-year interval reproducibility of a
      self-administered short FFQ, comprising 47 food items, and 8 frequency
      categories, among 1,918 subjects (844 males and 1,074 females) who participated
      in health check-up programs in Central Japan. RESULTS: Intakes of energy and 24
      nutrients along with 15 food groups estimated using the first questionnaire
      (FFQ1) were approximately equal to those using the second (FFQ2). Spearman's rank
      correlation coefficients (CCs) between intakes of nutrients quantified with FFQ1
      and FFQ2 in males were distributed as 0.74 - 0.66- 0.55 (maximum - median -
      minimum), and intraclass CCs (ICCs) as 0.85 - 0.78 - 0.67. Among females,
      Spearman's rank CCs were distributed as 0.73 - 0.62 - 0.54, and ICCs as 0.84 -
      0.77 - 0.69. Percentages of exact agreement, exact agreement plus agreement
      within adjacent categories and disagreement according to quintile categorization
      were 43%, 80%, and 1%, for males, and 42%, 79%, and 1% for females.
      Reproducibility figures were higher for the elderly than for young people in both
      sexes. CONCLUSIONS: Our FFQ yielded substantially high reproducibility and it may
      be applicable for assessing consumption of foods/food groups and energy and
      selected nutrients for the middle-aged and elderly population in Japan.

PMID- 17545698
TI  - The obligation to provide antiretroviral treatment in HIV prevention trials.
AB  - Providing antiretroviral therapy (ART) to participants who seroconvert during HIV
      prevention trials in developing countries is an ethical expectation. Promising
      treatment to the few seroconverters widens disparities within a resource-poor
      country and would be unjust. Such an assurance should be done in a way that also
      improves access to ART for others in the country. US funds for ART in poor
      countries from the PEPFAR should be available to all countries that host HIV
      prevention and clinical trials.

PMID- 17545699
TI  - Immune responses to abacavir in antigen-presenting cells from hypersensitive
      patients.
AB  - OBJECTIVES: A potentially life-threatening hypersensitive reaction accompanies
      the use of HIV nucleoside analogue abacavir (ABC) in 4-8% of Caucasian
      individuals. HLA-B*5701 and Hsp70 493T alleles have been shown to predict
      susceptibility to this hypersensitivity. DESIGN AND METHODS: This study was
      undertaken to provide a mechanistic understanding of the highly significant
      genetic association of HLA Class I and Hsp70 alleles with ABC hypersensitivity.
      RESULTS: In this study an ABC-induced localization of intracellular HSP70 to
      endosomal vesicles of antigen-presenting cells was demonstrated. This ABC
      stimulated redistribution of endogenous HSP70 was substantially higher in the
      genetically homogenous HLA-B*5701, Hsp70 493T ABC-hypersensitive individuals and
      ABC-naive individuals in comparison with the heterogeneous tolerant patients (P =
      0.023). Increased expression of HSP70 was also detected in the hypersensitive
      group as measured by flow cytometry (P = 0.032). Blocking of HSP70 and HSP70 cell
      surface receptors CD14 and TLR2 abrogated ABC-stimulated HSP70 redistribution in
      sensitized individuals to basal levels (P < 0.004). In addition, the use of
      TcRalphabeta and HLA-B57/58 antibodies also ablated the expression of HSP70.
      Cells expressing the activation markers CD40 were increased after ABC stimulation
      in the hypersensitive patients (P = 0.006). ABC-stimulated interferon-gamma
      levels were higher in hypersensitive patients in comparison with ABC-tolerant
      individuals with a mean of 123.54 versus 0 pg/ml (P = 0.001). CONCLUSION: The
      present data indicates that ABC stimulates an innate immune response and
      activates antigen-presenting cells via the endogenous HSP70-mediated Toll-like
      receptor pathway in genetically susceptible individuals potentially initiating
      the immuno-pathological hypersensitive response.

PMID- 17545700
TI  - Kaposi's sarcoma-associated herpesvirus-specific immune reconstitution and
      antiviral effect of combined HAART/chemotherapy in HIV clade C-infected
      individuals with Kaposi's sarcoma.
AB  - BACKGROUND: Kaposi's sarcoma-associated herpesvirus (KSHV) is endemic in South
      Africa and the clinical manifestation of AIDS-associated Kaposi's sarcoma (KS)
      represents a significant clinical problem. Whereas the positive effects of HAART
      on the regression of KS have been well established, less is known about the role
      of herpesvirus-specific cellular immunity in disease improvement. DESIGN: Thirty
      three treatment-naive HIV clade C-infected individuals with KS were randomly
      assigned into two treatment arms (HAART plus systemic chemotherapy versus HAART
      alone). KSHV-specific cellular immune responses, viral loads and clinical outcome
      were evaluated. METHODS: KSHV, Epstein-Barr virus and HIV-specific cellular
      immunity was measured using an IFN-gamma enzyme-linked immunospot assay in
      samples obtained at baseline and up to 11 months after treatment initiation. Cell
      associated KSHV viremia was determined by real-time polymerase chain reaction.
      RESULTS: Robust increases in CD4 cell counts and suppressed HIV viral loads were
      seen in parallel with significant increases in the KSHV-specific cellular immune
      responses over time. Although slowly increasing after 5 months, KSHV-specific T
      cell responses were significantly elevated only after 11 months, with both lytic
      and latent antigens being more frequently targeted. A trend towards better
      clinical outcome with HAART plus chemotherapy treatment was observed compared
      with HAART alone, and was accompanied by a significant reduction in cellular KSHV
      viral load in the HAART plus chemotherapy-treated subjects but not those treated
      with HAART alone after 11 months of treatment. CONCLUSION: The data show a
      temporal association between the clinical improvement of KS and the re-appearance
      of KSHV-specific cellular immunity, and demonstrate an effective suppression of
      KSHV viral replication using combination therapy.

PMID- 17545701
TI  - High frequency of rapid immunological progression in African infants infected in
      the era of perinatal HIV prophylaxis.
AB  - OBJECTIVES: To determine the natural history of HIV infection following
      peripartum single-dose nevirapine (sd-NVP) prophylaxis in a resource-limited
      country, and to assess implications for antiretroviral therapy (ART) roll-out
      programmes. METHODS: Infants of HIV-infected mothers in KwaZulu-Natal, South
      Africa, were tested on days 1 and 28 to detect intrauterine (IU) and intrapartum
      (IP) infection. Infant follow-up included monthly viral load and CD4 cell
      measurement. ART was initiated at infant CD4 cell% < or = 20%. RESULTS: In 740
      infants born to 719 HIV-infected women, mother-to-child transmission (MTCT) was
      10.3% (69% IU, 31% IP). Median viral load was higher in mothers of infants
      infected IP than IU (279 000 versus 86 600 copies/ml; P = 0.039) and lower in
      mothers of uninfected infants (median 26 750 copies/ml; P < 0.001). Peak viraemia
      was higher in infants infected IP than IU (5 160 000 versus 984 000 copies/ml; P
      < 0.001). Median viral load at birth in IU-infected infants (155 000 copies/ml)
      fell 1.4 log to 6510 copies/ml by day 5 and was beneath the detection limit using
      dried blood spot analysis in 38% of infants. CD4 cell% declined rapidly, to < or
      = 20% in 70% and < or = 25% in 85% [current World Health Organization (WHO)
      criteria for initiating ART] of infants by 6 months. CONCLUSIONS: MTCT was
      reduced by sd-NVP through an effect on IP transmission. Where MTCT occurred
      despite NVP, two-thirds of transmissions arose IU; IP-infected babies were born
      to mothers with very high viral load. Disease progression was particularly rapid,
      85% infants meeting WHO criteria for ART within 6 months. These findings argue
      for more effective MTCT-prevention programmes in resource-limited countries.

PMID- 17545702
TI  - HIV-1 pathogenesis differs in rectosigmoid and tonsillar tissues infected ex vivo
      with CCR5- and CXCR4-tropic HIV-1.
AB  - Gut-associated lymphoid tissue (GALT) has been identified as the primary target
      of HIV-1 infection. To investigate why GALT is especially vulnerable to HIV-1,
      and to determine whether the selective transmission of CCR5-using viral variants
      (R5) in vivo is the result of a greater susceptibility of GALT to this viral
      variant, we performed comparative studies of CXCR4-using (X4) and R5 HIV-1
      infections of human lymphoid (tonsillar) and rectosigmoid tissues ex vivo under
      controlled laboratory conditions. We found that the relative level of R5
      replication in rectosigmoid tissue is much greater than in tonsillar tissue. This
      difference is associated with the expression of the CCR5 co-receptor on
      approximately 70% of CD4 T cells in rectosigmoid tissue, whereas in tonsillar
      tissue it is expressed on fewer than 15% of CD4 T cells. Furthermore, tonsillar
      tissue responds to X4 HIV-1 infection by upregulating the secretion of CC
      chemokines, providing a potential CCR5 blockade and further resistance to R5
      infection, whereas gut tissue failed to increase such innate immune responses.
      Our results show that rectosigmoid tissue is more prone than tonsillar lymphoid
      tissue to R5 HIV-1 infection, primarily because of the high prevalence and
      availability of R5 cell targets and reduced chemokine blockade. The majority of
      CD4 T cells express CXCR4, however, and X4 HIV-1 readily replicates in both
      tissues, suggesting that although the differential expression of co-receptors
      contributes to the GALT vulnerability to R5 HIV-1, it alone cannot account for
      the selective R5 infection of the rectal mucosa in vivo.

PMID- 17545703
TI  - The safety of tenofovir disoproxil fumarate for the treatment of HIV infection in
      adults: the first 4 years.
AB  - OBJECTIVE: To characterize the safety profile of tenofovir disoproxil fumarate
      (DF) for the treatment of HIV infection in adults over the first 4 years of use.
      METHODS: A tenofovir DF expanded access program (EAP) was initiated in 2001;
      safety data were examined from this program and from the manufacturer's database,
      which contained reports of all postmarketing adverse drug reactions received up
      to 30 April 2005. Specific analyses were performed to characterize the renal
      safety of tenofovir DF. RESULTS: The EAP enrolled 10 343 patients; serious
      adverse events (SAEs) were reported in 631 (6%). A renal SAE of any type was
      observed in 0.5% of patients, and graded elevations in serum creatinine occurred
      in 2.2% of the patients evaluated. In a multivariate analysis, baseline risk
      factors for the development of increased serum creatinine on-study were elevated
      serum creatinine, concomitant nephrotoxic medications, low body weight, advanced
      age, and lower CD4 cell count. For postmarketing safety data (455 392 person
      years of exposure to tenofovir DF) the most commonly reported serious adverse
      drug reactions were renal events, with a distribution by type similar to that
      observed in the EAP. Bone abnormalities were infrequently reported in either the
      EAP or the postmarketing safety databases. No new unexpected toxicities were
      identified in postmarketing safety surveillance. CONCLUSIONS: The data
      demonstrate a favorable safety profile for tenofovir DF in the treatment of
      adults with HIV infection. Risk factors for development of nephrotoxicity can be
      identified and may be useful in managing those patients at greatest risk.

PMID- 17545704
TI  - Slower CD4 cell decline following cessation of a 3 month course of HAART in
      primary HIV infection: findings from an observational cohort.
AB  - OBJECTIVE: To investigate the effect of a short course of HAART during primary
      HIV infection (PHI) on rate of CD4 cell and viral load change. METHODS: Data
      following HAART cessation from 89 individuals (seroconverting 1999-2003) who
      chose to take a 3 month course of HAART at PHI were compared with 179 untreated
      controls in CASCADE, using linear and nonlinear random effects models.
      Participants were non-randomized but frequency matched for age, sex, risk factor,
      year of seroconversion and presentation within the first 6 months of
      seroconversion. Time to CD4 cell count < 350 cells/microl and initiation of
      clinically indicated antiretroviral therapy (ART) were also compared as competing
      risks. RESULTS: The rate of CD4 cell decline following therapy cessation appeared
      significantly slower among treated participants than untreated controls: losses
      of 51 cells/microl [95% confidence interval (CI), 32-69] and 77 cells/microl (95%
      CI, 65-89), respectively, 3 years after seroconversion (P = 0.011). Based on
      extrapolated data, viral loads also differed significantly at this point (4.09
      and 4.53 copies/ml, respectively). At 2 years, there was no significant
      difference in mean viral load levels: 4.31 copies/ml (95% CI, 4.14-4.48) and 4.47
      copies/ml (95% CI, 4.28-4.66), respectively. CASCADE seroconverters were more
      likely to reach CD4 cell count < 350 cells/microl or initiate clinically
      indicated ART (hazard ratio, 1.45; 95% CI, 1.02-2.05; P = 0.039). CONCLUSION: A
      short course of ART at PHI may delay CD4 cell decline. Confirmation of this
      requires a randomized clinical trial powered to address definitively the role of
      ART intervention in PHI (currently underway through SPARTAC).

PMID- 17545705
TI  - Antiviral activity, pharmacokinetics and safety of vicriviroc, an oral CCR5
      antagonist, during 14-day monotherapy in HIV-infected adults.
AB  - OBJECTIVE: To determine antiviral activity, pharmacokinetic properties, and
      safety of vicriviroc, an orally available CCR5 antagonist, as monotherapy in HIV
      infected patients. DESIGN AND METHODS: An ascending, multiple dose, placebo
      controlled study randomized within treatment group. Forty-eight HIV-infected
      individuals were enrolled sequentially to dose groups of vicriviroc: 10, 25 and
      50 mg twice a day, and were randomly assigned within group to receive vicriviroc
      or placebo (16 total patients/group) for 14 days. RESULTS: Significant reductions
      from baseline HIV RNA after 14 days were achieved in all active treatment groups.
      Suppression of viral RNA persisted 2-3 days beyond the end of treatment.
      Reductions of 1.0 log10 HIV RNA or greater were achieved in 45, 77 and 82% of
      patients in the three groups, respectively. Eighteen, 46 and 45% of subjects
      achieved declines of 1.5 log10 or greater in HIV RNA in the three groups,
      respectively. Vicriviroc was rapidly absorbed with a half-life of 28-33 h,
      supporting once-daily dosing. Pharmacokinetic parameters were dose linear; steady
      state was achieved by day 12. Two subjects experienced a transient detectable X4
      tropic virus. Vicriviroc was well tolerated in all dose groups. The frequency of
      adverse events was similar in the vicriviroc and placebo groups: 72 and 62%,
      respectively. The most frequently reported adverse events included headache,
      pharyngitis, nausea and abdominal pain, which were not dose related. CONCLUSION:
      Whereas all doses were well tolerated and produced significant declines in plasma
      HIV RNA, total oral daily doses of 50 or 100 mg vicriviroc monotherapy for 14
      days appeared to provide the most potent antiviral effect in this study.

PMID- 17545706
TI  - Hepatotoxicity in an African antiretroviral therapy cohort: the effect of
      tuberculosis and hepatitis B.
AB  - OBJECTIVE: Hepatotoxicity is a significant complication of antiretroviral therapy
      (ART). We assessed the incidence of and risk factors for hepatotoxicity among HIV
      infected individuals on ART in South Africa. DESIGN: We conducted a retrospective
      cohort study in a workplace HIV care program in South Africa which uses a first
      line regimen of efavirenz, zidovudine, and lamivudine and provides routine
      clinical and laboratory monitoring. METHODS: We included subjects with baseline
      and follow-up alanine transaminase and aspartate aminotransferase tests. Severe
      hepatotoxicity cases were identified during the first 12 months of ART. Potential
      risk factors, including concomitant medication use, tuberculosis, and hepatitis B
      and C, were determined from clinical records, database queries, and serological
      testing. Associations with hepatotoxicity were investigated using Cox
      proportional hazards modeling. RESULTS: Of the 868 subjects (94% male, median age
      41 years), the median nadir CD4 cell count was 136/microl, 25% received
      concomitant tuberculosis treatment during ART, and 17% of a randomly selected
      subset were positive for hepatitis B surface antigen (HBsAg). We identified 7.7
      episodes of severe hepatotoxicity per 100 person-years. Tuberculosis treatment
      increased risk 8.5 fold, positive HBsAg 3.0 fold, and nadir CD4 cells count <
      100/microl 1.9 fold. Importantly, the fraction of patients with severe
      hepatotoxicity on ART (4.6%) was similar to the fraction with liver enzyme
      elevations > 5 times the upper limit of normal before starting ART (4%).
      CONCLUSIONS: In this African ART cohort, we found a low incidence of and minimal
      morbidity due to hepatotoxicity. HBsAg and concomitant tuberculosis therapy
      significantly increased the risk of hepatotoxicity.

PMID- 17545707
TI  - The role of compartment penetration in PI-monotherapy: the Atazanavir-Ritonavir
      Monomaintenance (ATARITMO) Trial.
AB  - OBJECTIVES: To limit exposure to anti-HIV drugs and minimize risk of long-term
      side effects, studies have looked at the possibility of simplified maintenance
      strategies. Ritonavir-boosted protease-inhibitor (PI)-monotherapies are an
      attractive alternative, but limited compartmental penetration of PI remains a
      concern. DESIGN: Non-comparative 24-week pilot study. METHOD: Ritonavir-boosted
      atazanavir (ATV/r) monotherapy administered to fully suppressed patients (>3
      month HIV RNA < 50 copies/ml). Plasma was obtained every 4 weeks and
      cerebrospinal fluid (CSF) and semen at W24. RESULTS: Two patients (7%) failed
      ATV/r monotherapy. One patient was subsequently identified as a protocol violator
      since he had a previous history of treatment failure under indinavir. The second
      patient deliberately decided to stop treatment after W20. Excluding failing
      patients, individual measurements of HIV RNA in patients having occasional viral
      'blips' was found in five patients. At W24, 3/20 patients had elevated viral
      loads in CSF (HIV RNA > 100 copies/ml), and 2/15 in semen, despite viral
      suppression in plasma (< 50 copies/ml). Samples with elevated HIV RNA (> 500
      copies/ml) in CSF were all wild type. The mean ATV drug concentration ratio
      (CSF/blood, n = 22) was 0.9%. Indicators of altered immune activation (CD8CD38 C
      reactive protein) remained unchanged. CONCLUSION: This study supports previous
      results indicating the potential use of PI-based mono-maintenance therapies.
      However, our results in CSF cautions against the uncontrolled use of PI-based
      monotherapies.

PMID- 17545708
TI  - CCR5 density levels on primary CD4 T cells impact the replication and Enfuvirtide
      susceptibility of R5 HIV-1.
AB  - OBJECTIVE AND DESIGN: Studies in cell lines have demonstrated that CCR5
      coreceptor levels influence the replication efficiency and Enfuvirtide (T-20)
      susceptibility of R5 HIV-1 strains. At present, however, the role that CCR5
      levels on primary CD4 T cells--which are markedly lower than in cell lines and
      vary only approximately fivefold among most donors--may play in virus replication
      levels or susceptibility to T-20 is not known. In the present study we evaluated
      the impact of differences in CCR5 levels among donor CD4 T cells on the infection
      efficiency and T-20 susceptibility of R5 HIV-1. METHODS: CD4 and CCR5 density
      levels were determined by Quantitative FACS analysis. Virus infectivity assays
      were conducted in cell lines and primary cells. Associations between coreceptor
      density, virus replication and T-20 sensitivity were tested using the Spearman's
      correlation test. RESULTS: We found a positive correlation (r, 0.55; P = 0.011)
      between CCR5 density levels on primary CD4 T cells and replication of R5 HIV-1.
      In cell lines expressing physiologically relevant levels of CD4 and CCR5, T-20
      was significantly more potent in cells with low CCR5 levels. In addition, T20 50%
      inhibitory concentrations for R5 HIV-1 replication varied approximately 100-fold
      among primary cells from different donors and they were positively correlated
      with CCR5 density values (r, 0.84; P = 0.00004). CONCLUSIONS: These results
      suggest that CCR5 density levels in HIV-1 patients may impact the activity of T
      20 against R5 strains and that therapeutic approaches to alter CCR5 density may
      potentiate T-20.

PMID- 17545709
TI  - Epidemiology, diagnosis and treatment of chronic hepatitis B in HIV-infected
      patients (EPIB 2005 STUDY).
AB  - OBJECTIVE: To describe the characteristics of hepatitis B (HBV) infection in HIV
      infected patients and the impact of anti-HBV treatments. PATIENTS AND METHODS:
      All the patients with past or present chronic HBV infection seen in October 2005
      in 17 French hospitals were included. Data were retrospectively collected from
      their first visit in a time-dependent manner, through a detailed standardized
      questionnaire. RESULTS: Among 477 HBV-infected patients, 261 (55%) were co
      infected with HIV. The HBV-HIV co-infected patients underwent fewer serological,
      virological and histological evaluations. Initial positive HBe antigenemia (HBe
      Ag) was more frequent in these patients (57.9 versus 28.6%; P < 10), as was
      cirrhosis on the initial liver biopsy (17.9 versus 7.6%; P = 0.05). Throughout
      the mean 5-year follow-up, HBe Ag loss was less frequent (P = 0.04), as was HBe
      seroconversion (incidence rate 2.6 versus 10/100 patient-years; P < 10). HBe Ag
      loss was associated with fibrosis improvement (METAVIR score -0.5 +/- 0.4 versus
      +0.2 +/- 0.6 if persistent positive HBe Ag, P = 0.01). In co-infected patients on
      tenofovir, adefovir or interferon, HBe seroconversions were seen in patients on
      combined HBV treatment, the use of which is increasing (58% in 2005).
      Nevertheless, no significant difference in virological, immunological or
      biochemical evolution was observed between these different treatments.
      CONCLUSIONS: In HBV-HIV co-infected patients, the assessment of HBV infection
      still needs to be improved, the HBV wild-type remains predominant, and HBe Ag
      loss is rare and associated with a better histological evolution. There is
      insufficient evidence of the superiority of combined HBV treatment, and this
      still needs be demonstrated in long term studies.

PMID- 17545710
TI  - The cost effectiveness of antiretroviral treatment strategies in resource-limited
      settings.
AB  - BACKGROUND: Optimal resource allocation for antiretroviral treatment (ART) in
      developing countries requires assessment of different strategies for drug
      treatment and laboratory monitoring. OBJECTIVES: To compare costs and outcomes
      for 10 000 simulated HIV-infected patients followed every 6 months for 10 years
      in a limited-resource setting. METHOD: Five nested strategies, with and without
      the availability of a second-line treatment regimen, were simulated: (a) no ART
      (NO ART); (b) with ART but without any laboratory markers of HIV other than
      positive serology (ART ONLY); (c) ART plus total lymphocyte count (TLC); (d) ART
      plus CD4 cell counts (CD4); and (e) ART plus CD4 cell count plus viral load
      measurement (VL). Baseline prices of CD4 cell count and viral load measurements
      were $5.00 and $25.00 per test, respectively. RESULTS: With no second-line
      treatment available, treating 10 000 patients with ART ONLY compared with NO ART
      would cost $14.49 million [95% confidence interval (CI), 14.45-14.52] and would
      generate an additional 23 060 quality-adjusted life years (QALYS) (95% CI, 22 770
      23 360) for a median incremental cost effectiveness ratio (ICER) of $628/QALY.
      Median ICER values per QALY for CD4 and VL strategies are $238 and $16 139,
      respectively, when second-line treatment is unavailable. With second-line ART
      available, the corresponding median ICER values are $8636, and $14 670.
      CONCLUSIONS: In the absence of second-line ART, the CD4 strategy is a more cost
      effective laboratory testing strategy for managing HIV infection than either TLC
      or VL. Availability of second-line ART plus CD4 cell count and/or viral load
      measurement would save additional lives, but at high incremental cost.

PMID- 17545711
TI  - Surveillance of mother-to-child transmission prevention programmes at
      immunization clinics: the case for universal screening.
AB  - BACKGROUND: Surveillance programmes for prevention of mother-to-child
      transmission of HIV (PMTCT) fail to quantify numbers of infant HIV infections
      averted, often because of poor postnatal follow-up. Additionally, infected
      infants are often not identified early and only gain access to comprehensive HIV
      care and treatment late in their disease. METHODS: Anonymous, unlinked, HIV
      prevalence testing was conducted on dried blood spot (DBS) samples from all
      infants attending 6 week immunization clinics at seven primary health care
      clinics offering PMTCT. Samples were tested for HIV antibodies (indicating
      maternal HIV infection) and those determined to be from HIV-exposed infants were
      tested for HIV RNA by polymerase chain reaction. Infant and child mortality rates
      were determined using birth histories. RESULTS: Samples were collected from 2489
      infants aged 4-8 weeks. HIV antibodies were identified in 931 infants [37.4%; 95%
      confidence interval (CI), 35.4-39.4], of whom 188 were HIV RNA positive. The
      estimated vertical transmission rate (VTR) was 20.2% (95% CI, 17.8-23.1%); 7.5%
      of all infants at this age were infected. Amongst mothers who reported that they
      had taken single-dose nevirapine for PMTCT, VTR was 15.0%. Amongst women who
      reported being HIV uninfected but whose infants had HIV antibodies, VTR was
      30.5%. Infant mortality rates in KwaZulu Natal increased from 28/1000 live births
      in 1990-1994 to 92/1000 in 2000-2004. CONCLUSIONS: Anonymous HIV prevalence
      screening of all infants at immunization clinics is feasible to monitor the
      impact of PMTCT programmes on peripartum infection; linked screening could
      identify infected children early for referral into care and treatment programmes.

PMID- 17545712
TI  - 'Are you on the market?': a capture-recapture enumeration of men who sell sex to
      men in and around Mombasa, Kenya.
AB  - BACKGROUND: Men who have sex with men (MSM) are highly vulnerable to HIV
      infection, but this population can be particularly difficult to reach in sub
      Saharan Africa. We aimed to estimate the number of MSM who sell sex in and around
      Mombasa, Kenya, in order to plan HIV prevention research. METHODS: We identified
      77 potential MSM contact locations, including public streets and parks, brothels,
      bars and nightclubs, in and around Mombasa and trained 37 MSM peer leader
      enumerators to extend a recruitment leaflet to MSM who were identified as 'on the
      market', that is, a man who admitted to selling sex to men. We captured men on
      two consecutive Saturdays, 1 week apart. A record was kept of when, where and by
      whom the invitation was extended and received, and of refusals. The total
      estimate of MSM who sell sex was derived from capture-recapture calculation.
      RESULTS: Capture 1 included 284 men (following removal of 15 duplicates); 89 men
      refused to participate. Capture 2 included 484 men (following removal of 35
      duplicates); 75 men refused to participate. Of the 484 men in capture 2, 186 were
      recaptures from capture 1, resulting in a total estimate of 739 (95% confidence
      interval, 690-798) MSM who sell sex in the study area. CONCLUSIONS: We estimated
      that 739 MSM sell sex in and around Mombasa. Of these, 484 were contacted through
      trained peer enumerators in a single day. MSM who sell sex in and around Mombasa
      represent a sizeable population who urgently need to be targeted by HIV
      prevention strategies.

PMID- 17545713
TI  - Drug-resistance surveillance among newly HIV-1 diagnosed individuals in Buenos
      Aires, Argentina.
AB  - OBJECTIVE: Our objective was to estimate primary resistance in an urban setting
      in a developing country with a long history of antiretroviral delivery and high
      coverage levels. DESIGN: We carried out a resistance surveillance study according
      to WHO HIV-Resistance Guidelines. METHODS: Blood samples were collected from 323
      drug-naive HIV-1 infected individuals diagnosed at two HIV voluntary counselling
      and testing centers in Buenos Aires. Viral-load, CD4 cell counts and detuned
      assays were performed on all samples. The pol gene was sequenced and the
      resistance profile determined. Phylogenetic analysis was performed by neighbor
      joining trees and bootscanning analysis. RESULTS: We found that 12 (4.2%) of the
      284 samples sequenced harbored primary resistance mutations, of which K103N, M41L
      and V108I were most prevalent. Phylogenetic analysis revealed evidence for the
      transmission of the K103N mutation among the drug-naive population. The
      proportion of recent infections identified by the detuned assay was 10.1%.
      CONCLUSIONS: Levels of primary resistance in Buenos Aires are still low, despite
      a long history of ARV delivery and high coverage levels.

PMID- 17545714
TI  - Men who have sex with men and their HIV epidemics in Africa.

PMID- 17545715
TI  - Antiviral therapy for hepatitis C virus recurrence after liver transplantation in
      HIV-infected patients: outcome in the Bonn cohort.
AB  - Recurrent hepatitis C is a major cause of mortality in HIV/hepatitis C virus
      (HCV)-co-infected patients after orthotopic liver transplantation. We report
      sustained viral clearance in all four transplanted HIV/HCV-positive patients
      treated with pegylated interferon/ribavirin. Early therapy after HCV recurrence,
      tailoring treatment duration to the individual decline in HCV-RNA and the
      management of side effects are key factors for improved efficacy. At experienced
      centres interferon treatment is a valuable option for recurrent hepatitis C in
      HIV-positive patients.

PMID- 17545716
TI  - Transmission of multidrug-resistant HIV-1: 5 years of immunological and
      virological survey.
AB  - Multidrug resistant HIV-1 acquired at the time of primary infection in two
      patients persisted for at least 5 years with and without treatment. In each
      patient, only one back mutation to wild-type codon in the protease gene occurred,
      and that was concomitantly associated with a marked CD4 cell count decrease. In
      both cases, infection was caused by CCR5 viruses and no rapid clinical
      progression to AIDS after primary infection was observed.

PMID- 17545717
TI  - Fosamprenavir/ritonavir plus tenofovir does not affect amprenavir
      pharmacokinetics: no effect of tenofovir.
AB  - The effect of tenofovir disoproxil fumarate (TDF) in combination with two boosted
      fosamprenavir regimens on amprenavir pharmacokinetic parameters was assessed in
      this prospective phase I crossover study with 30 healthy volunteers. The co
      administration of TDF 300 mg once a day with fosamprenavir/ritonavir 1400/200 mg
      or 1400/100 mg once a day has no effect on the pharmacokinetics of amprenavir and
      results in non-significant increases of ritonavir pharmacokinetic parameters,
      suggesting that no dose modification is necessary when combining
      fosamprenavir/ritonavir with TDF.

PMID- 17545718
TI  - Cutaneous reactions with tenofovir disoproxil fumarate: a report of nine cases.
AB  - Adverse drug reactions causing the early discontinuation of therapy are common in
      patients with HIV infection. Hypersensitivity consisting mainly of a
      maculopapular rash on the face, extremities and trunk has been observed at a rate
      higher than expected in patients treated with tenofovir at our clinics. We
      therefore examined nine patients with suspected tenofovir hypersensitivity
      reactions in two indigent care HIV clinics. Type I and type IV hypersensitivity
      may be involved as immunological mechanisms.

PMID- 17545719
TI  - Pharmacokinetics of once-daily tenofovir, emtricitabine, ritonavir and
      fosamprenavir in HIV-infected subjects.
AB  - HAART has decreased the incidence of AIDS and death among HIV-infected
      individuals dramatically. This approach often becomes cumbersome to patients,
      involving multiple drugs administered on varying schedules. We investigated the
      pharmacokinetics, efficacy, and tolerability of a once-daily regimen of
      fosamprenavir, tenofovir, emtricitabine and ritonavir in HIV-infected treatment
      naive subjects. No clinically significant interaction between the drugs was
      noted, and the regimen showed good efficacy and tolerability over the course of
      48 weeks.

PMID- 17545720
TI  - The toll-like receptor 4 Asp299Gly variant and tuberculosis susceptibility in HIV
      infected patients in Tanzania.
AB  - Toll-like receptor 4 (TLR4) plays an important role in the pattern recognition of
      Mycobacterium tuberculosis, and polymorphisms in the TLR4 gene influence the
      function of the receptor. We therefore investigated in a cohort of HIV-infected
      Tanzanian patients whether the Asp299Gly TLR4 polymorphism is associated with the
      development of active tuberculosis. We found a greater risk of developing active
      tuberculosis as well as a reduction in CD4 T-cell counts in patients with the
      Asp299Gly TLR4 polymorphism.

PMID- 17545721
TI  - Effect of GB virus C co-infection on response to generic HAART in African
      patients with HIV-1 clade C infection.
AB  - In 38 African AIDS patients initiating generic HAART, GB virus C (GBV-C) RNA
      positive patients retained GBV-C viraemia during 52 weeks of HAART, had a faster
      decline in HIV viral load (P = 0.03), fewer opportunistic infections (14.3 versus
      50%, P = 0.18), and suffered no serious adverse events (none versus 61%, P =
      0.008) compared with patients without GBV-C. GBV-C co-infection may be associated
      with a beneficial effect on African AIDS patients treated with generic HAART.

PMID- 17545722
TI  - Expression of PD-L1, a marker of disease status, is not reduced by HAART in
      aviraemic patients.
AB  - Anergy and defective immune responses are characteristic of chronic HIV-1
      infection. The programmed death 1 (PD-1)/PD-1 ligand (PD-L1) pathway appears to
      be involved in downregulating T-cell functionality. We found raised levels of PD
      L1 in aviraemic chronically infected HIV-1-positive patients, which may
      contribute to incomplete immune reconstitution after treatment with HAART.

PMID- 17545723
TI  - A child with HIV-associated transient cerebral arteriopathy.

PMID- 17545724
TI  - Discontinuation of non-nucleoside reverse transcriptase inhibitor-based
      antiretroviral therapy: clinical implications in patients on CD4 T-cell-guided
      treatment interruption.

PMID- 17545725
TI  - Fatal myocardial co-infection by Toxoplasma gondii and Parvovirus B19 in an HIV
      patient.

PMID- 17545726
TI  - Successful long-course after failure of short-course desensitization in a patient
      with severe hypersensitivity reaction to enfuvirtide.

PMID- 17545727
TI  - Misleading results of screening for illicit drugs during efavirenz treatment.

PMID- 17545728
TI  - Alopecia associated with ritonavir-boosted atazanavir therapy.

PMID- 17545729
TI  - Efavirenz: innocent bystander or direct nephrotoxin?

PMID- 17545731
TI  - Topographic patterns of brain functional impairment progression according to
      clinical severity staging in 116 Alzheimer disease patients: FDG-PET study.
AB  - The study aimed to explore topographic progression pattern of brain functional
      impairment according to clinical stage in Alzheimer disease (AD). One hundred and
      sixteen AD patients and 25 normal subjects underwent a [18F] fluorodeoxyglucose
      positron emission tomography scan. Regional cerebral glucose metabolism was
      compared between severity groups based on the Clinical Dementia Rating through
      voxel-based analyses. As clinical severity progressed, hypometabolic areas
      gradually increased, involving initially posterior cingulate cortex, later
      temporoparietal, and finally frontal and some subcortical areas. The results
      indicate that progression patterns of hypometabolism in AD are close to that of
      typical neuropathology, but that they do not fully coincide with it.

PMID- 17545732
TI  - Heritability of magnetic resonance imaging (MRI) traits in Alzheimer disease
      cases and their siblings in the MIRAGE study.
AB  - Magnetic resonance imaging (MRI) traits can serve as more specific measures of
      degenerative or cerebrovascular brain injury than can be ascertained through
      personal history, risk factors, clinical signs, or symptoms. They are potentially
      useful intermediate phenotypes for genetic studies of Alzheimer disease (AD).
      Recent studies have estimated heritability of white matter hyperintensity (WMH)
      among cognitively normal family members to be between 0.55 and 0.73. Persons
      discordant for AD are expected to have substantially different MRI phenotype
      distributions; our goal was to determine whether MRI traits in siblings
      discordant for AD are heritable. We measured cerebral atrophy, medial temporal
      atrophy (MTA), WMH, and a rating of cerebrovascular disease (CVR) via MRI in 815
      participants from 424 families of the Multi-Institutional Research in Alzheimer's
      Genetic Epidemiology Study. Residual heritability after adjustment for covariates
      ranged from 0.17 (P=0.009) for MTA to 0.57 (P=10(-7)) for CVR. The number of APOE
      epsilon4 alleles was significantly associated with WMH (P=0.01) and CVR (P=0.005)
      but not cerebral atrophy (P=0.25) or MTA (P=0.83). Heritability remained
      significant and high after adjusting for APOE genotype, suggesting that a
      substantial proportion of the additive genetic variation in these MRI traits is
      explained by other genes. In the Multi-Institutional Research in Alzheimer's
      Genetic Epidemiology Study of AD-discordant siblings, MRI traits are heritable
      and are potential endophenotypes for genetic association studies.

PMID- 17545733
TI  - Impact of patient selection criteria on prevalence estimates and prevalence of
      diagnosed dementia in a Medicaid population.
AB  - OBJECTIVES: This study estimated the prevalence of diagnosed dementia among
      Indiana Medicaid beneficiaries in 2004. The dependence of prevalence estimates
      upon use of several patient selection criteria to identify patients with dementia
      also was evaluated. METHODS: Indiana Medicaid claims data were analyzed for the
      period July 1, 2002 to December 31, 2004. An expert panel survey was conducted to
      assess perceived specificity of ICD codes used in previous studies to define
      dementia. Prevalence estimates were calculated with varying levels of each
      selection criteria, that is, ICD code set, interval of data examined, and number
      of occurrences of dementia-related claims. To assess specificity and sensitivity
      of the dementia patient selection criteria, Minimum Data Set data for a subset of
      beneficiaries that resided in a nursing home any time in 2004 were examined.
      RESULTS: Depending on the patient selection criteria used, estimates of
      prevalence of diagnosed dementia for individuals 40 years old or older varied
      from 7.7% to 15.3%, whereas prevalence estimates for individuals 60 years old or
      older varied from 14.5% to 26.6%. When the following selection criteria were
      used: (1) occurrence of one or more dementia-related claims, (2) the expert panel
      ICD set, and (3) up to 30 months of data for defining dementia, the prevalence
      estimates in the Indiana Medicaid population were 10.9% for individuals 40 years
      old or older and 20.3% for individuals 60 years old or older. CONCLUSIONS:
      Careful selection of claims-based criteria for identifying patients with dementia
      is important because the criteria may affect estimates by 100%. Prevalence of
      diagnosed dementia among Indiana Medicaid beneficiaries was 3 to 4 times higher
      than the reported prevalence from a decade ago in Medicaid populations of other
      states, even when the same patient selection criteria were used. A number of
      factors beyond increased occurrence of the disease including increased screening,
      greater likelihood of recording dementia codes in claims, or other factors may be
      responsible. The combination of patient selection criteria used in this study had
      good sensitivity, specificity, and accuracy when compared with Minimum Data Set
      data.

PMID- 17545734
TI  - Symptoms of memory loss as predictors of cognitive impairment?: the use and
      reliability of memory ratings in a clinic population.
AB  - BACKGROUND: Symptoms of memory loss are very common with estimated prevalence
      between 22% and 50% in those older than 65 years of age. Those with symptoms of
      memory loss and impaired performance on memory tests are at high risk of
      progression to Alzheimer disease. The relative importance of different aspects of
      the clinical history in predicting cognitive impairment is uncertain. METHODS:
      Fifty-six patients with symptoms of memory loss were recruited from the National
      Hospital for Neurology and Neurosurgery. A clinician recorded type and duration
      of memory symptoms as perceived by the patient and their informant, and use of
      memory aids. All patients subsequently underwent magnetic resonance imaging (MRI)
      and neuropsychologic testing. FINDINGS: (i) Informant, but not patient, ratings
      of memory were associated with performance on tests of memory function and with
      hippocampal size on MRI. (ii) Decreased use of memory aids and shorter duration
      of memory symptoms were more common in those with memory impairment.
      INTERPRETATION: In a clinical setting, information gathered from the history was
      associated with cognitive impairment on memory testing and brain appearances on
      MRI. The history from a close informant is particularly important being more
      strongly predictive of cognitive impairment (P=0.0002) than subjective symptoms,
      use of memory aids or duration of symptoms.

PMID- 17545735
TI  - Dementia diagnosis disclosure: a study of patient and caregiver perspectives.
AB  - This paper reports the findings of a descriptive, exploratory, qualitative study
      of patient and caregiver perspectives of the disclosure of a dementia diagnosis.
      Data were collected at 3 points in time: (1) the disclosure meeting, (2) patient
      and caregiver interviews, and (3) focus group interviews. Thirty patient
      caregiver dyads participated in the disclosure meetings at the Geriatric Day
      Hospital at the Ottawa Hospital, Ottawa, Canada. Within a week of the disclosure
      of diagnosis, 27 (90%) patients and 29 (97%) caregivers were interviewed in their
      homes, and 12 caregivers participated in 3 focus group interviews within 1 month
      after the disclosure meeting. Most patients and caregivers said they preferred
      full disclosure of the diagnosis. Patients expressed satisfaction with the
      physician providing the diagnosis and with their caregivers being present at the
      disclosure meeting, however, wanted more information about their condition.
      Caregivers provided further insight regarding the patient response, and suggested
      the need to emphasize hope in the face of a difficult diagnosis, the use of
      progressive disclosure to allow the person (and caregivers) to prepare, and the
      provision of detail about the disease and its progression.

PMID- 17545736
TI  - Documentation, assessment, and treatment of aggression in patients with newly
      diagnosed dementia.
AB  - Practice guidelines recommend a search for underlying biopsychosocial causes and
      initial use of nonpharmacologic interventions. Using guidelines as a benchmark
      for standard care, we examined medical records to assess the documentation,
      assessment, and treatment of aggression in patients newly diagnosed with
      dementia. Study participants were at least 60 years old and diagnosed with
      dementia at the Michael E. DeBakey VA Medical Center in Houston, TX, from 2001 to
      2004. Of 385 eligible patients screened by telephone using 3 probes from the
      Ryden Aggression Scale, 75 had positive response to 1 or more of 3 probes from
      the Ryden. Medical records of these patients were reviewed for 12 months before
      and 3 months after telephone screening. Aggression had been documented in 31
      (42%), nonpharmacologic interventions had been used in 11 (35%), and
      pharmacologic interventions had been used in all 31. Among the 44 patients
      without previously documented aggression, pharmacologic interventions were used
      in 34 (79%) patients. Patients with documented aggression had more psychiatric
      comorbidities and received more psychotropic medications than patients with
      undocumented aggression. We conclude that dementia patients should be
      systematically screened for aggression and that new strategies to increase use of
      nonpharmacologic interventions and decrease use of pharmacologic interventions,
      particularly antipsychotics, should be identified.

PMID- 17545737
TI  - The sex specificity of navigational strategies in Alzheimer disease.
AB  - Alzheimer disease (AD) is associated with navigational impairments that limit
      functional independence. We have now examined the role of cognitive and
      perceptual mechanisms in the navigational impairment of AD to test the hypothesis
      that men and women with AD may focus on different navigational cues. We conducted
      navigational, neuropsychologic, and psychophysical testing in men and women from
      3 groups: older normal controls, patients with mild cognitive impairment, and
      patients with AD. Men and women showed parallel declines in navigational
      capacities from the older normal control, to the mild cognitive impairment, to
      the AD groups with men and women making similar numbers of errors but different
      types of errors. There were small sex differences in neuropsychologic and
      psychophysical performance but large sex differences in how those measures
      related to navigational capacity: men showed strong links between visual motion
      processing and navigation. Women showed strong links between verbal capacities
      and navigation. The findings of these cross-sectional comparisons suggest that
      there may be sex differences in the progressive navigational decline of AD: men
      and women who are impaired to the same degree may suffer somewhat different
      patterns of decline with men relying more on visuospatial processing and women
      relying more on verbal mediation.

PMID- 17545738
TI  - Perception of emotions on happy/sad chimeric faces in Alzheimer disease:
      relationship with cognitive functions.
AB  - AIMS: To investigate the ability to recognize facial emotions in patients with
      Alzheimer disease (AD). Happiness and sadness, fundamental emotions that are
      easily recognized across cultures, were evaluated. Results were further analyzed
      in relation to demographic, clinical, and neuropsychologic characteristics.
      METHODS: A test exploring recognition of facial emotions using chimeric faces
      based on Jaynes' happy and sad faces was administered to 71 patients with
      probable AD. RESULTS: The ability to identify positive and negative facial
      emotions was largely preserved in AD subjects. Impaired recognition of facial
      emotions was found in 27%. Poor test performance was associated with low scores
      on constructional praxis and nonverbal memory tasks. CONCLUSIONS: Decoding of
      emotional facial expressions seems to be differently affected in relation to
      patients' neuropsychologic profile, as poor test performance closely correlated
      with nonverbal cognitive impairment. This emotion-discrimination disorder likely
      characterizes the behavior of a subset of AD patients with predominant right
      hemisphere dysfunction. A preserved ability to process the emotional features of
      faces may have an important role in the management of demented patients, and
      suggests the use of nonverbal communication as an integrative/alternative system.
      The simple test used in our study may be a useful clinical tool to explore
      emotional behavior in demented subjects.

PMID- 17545739
TI  - A 24-week randomized, controlled trial of memantine in patients with moderate-to
      severe Alzheimer disease.
AB  - This study examined the efficacy and safety of memantine monotherapy in patients
      with moderate-to-severe Alzheimer disease (AD). Patients not receiving a
      cholinesterase inhibitor (N=350) were randomized to receive memantine (20 mg/d)
      or placebo during this 24-week, double-blind, placebo-controlled trial.
      Prospectively defined analyses failed to demonstrate a statistically significant
      benefit of memantine treatment compared with placebo on the Severe Impairment
      Battery (SIB) at week 24 end point, although a significant advantage was observed
      for memantine at weeks 12 and 18. The 19-item Alzheimer's Disease Cooperative
      Study-Activities of Daily Living Scale (ADCS-ADL19) did not differ significantly
      between groups in any analysis. Clinician's Interview-Based Impression of Change
      plus Caregiver Input (CIBIC-Plus) did not significantly favor memantine at week
      24 despite a significant advantage for memantine at weeks 12 and 18. Other
      secondary outcomes showed no significant treatment differences. Post hoc analyses
      of potentially confounding covariates and alternative methods of imputing missing
      data did not substantially alter the results. Because of the violations of
      normality assumptions for the SIB and ADCS-ADL19, nonparametric analyses were
      performed; statistically significant benefit of memantine over placebo was
      demonstrated at week 24 for the SIB but not the ADCS-ADL19. The type and
      incidence of adverse events were similar in both groups.

PMID- 17545740
TI  - Diabetes and parkinsonian signs in older persons.
AB  - We examined the relation of type 2 diabetes mellitus to parkinsonian signs in
      older persons. Participants were 1030 women and men (mean age 80.3 y, education
      14.5 y, Mini-Mental State Examination 27.9) without dementia or Parkinson
      disease, enrolled in the Rush Memory and Aging Project, an epidemiologic study of
      aging. We used separate linear and logistic regression models, adjusted for age,
      sex, and education, to examine the relation of diabetes, identified by history
      and medication inspection, to each of the scores of global parkinsonian signs and
      4 separate parkinsonian signs. Diabetes was present in 140 (14%) participants.
      Most participants had mild parkinsonian signs. Diabetes was associated with a
      more severe global parkinsonian signs score (beta=0.20, SE=0.10, P=0.05) and
      postural reflex impairment-gait disturbance (beta=0.40, SE=0.17, P=0.02), but not
      with bradykinesia, rigidity, or tremor. Associations were no longer significant
      after controlling for vascular risk factors or conditions, particularly body mass
      index and congestive heart failure. Overall, there was no evidence that vascular
      variables modified the relation of diabetes to parkinsonian signs. In summary, we
      found that diabetes was associated with parkinsonian signs, especially postural
      reflex impairment-gait disturbance, and that vascular factors may play a role in
      this association.

PMID- 17545741
TI  - Patients with dementia with lewy bodies have more impaired quality of life than
      patients with Alzheimer disease.
AB  - The primary aim of this study was to compare quality of life (QoL) in patients
      with Dementia with Lewy Bodies (DLB) and patients with Alzheimer disease (AD).
      The secondary aim of this study was to investigate determinants of QoL in DLB.
      Thirty-four patients with DLB at the Neuropsychiatry clinic, University Hospital
      MAS, Malmo, Sweden, were included in a cross-sectional study. These patients were
      matched to 34 patients with AD. Two QoL instruments, the EQ-5D instrument and the
      Quality of Life-Alzheimer disease (QoL-AD) instrument, were applied in this
      study. Both instruments were administered to both patients and caregivers.
      Patients with DLB in this study have significantly lower QoL than patients with
      AD regardless of instrument or whether patient or caregiver-reported QoL was
      used. Furthermore, this study shows that important determinants of QoL in DLB
      include Neuropsychiatric Inventory score, independency in instrumental activities
      of daily living, whether the patient is living with the caregiver and the
      presence of apathy and delusions.

PMID- 17545742
TI  - The diagnosis and course of frontotemporal dementia.
AB  - The course of frontotemporal dementia (FTD) is examined in a prospective,
      incipient clinical cohort. Three hundred nineteen patients were followed yearly
      for an average of 3.6 years. The relative frequencies at presentation were
      Behavioral variety (FTD-bv) 37.6%, Primary Progressive Aphasia (PPA) 31.6%,
      possible PPA 10.6%, Corticobasal Syndrome (CBDS) and Progressive Supranuclear
      Palsy (PSP) 8.1%, Semantic Dementia (SD) 6.6%, and possible FTD 5.3%. The age of
      onset was significantly lower in the FTD-bv and SD groups than in the rest, but
      survival and sex distribution was similar in all groups. The evolution is
      characterized by the appearance of additional FTD syndromes in two-thirds of the
      patients. A significant association of SD with FTD-bv and CBDS/PSP with PPA was
      found. The Frontal Behavioral Inventory was highly sensitive and specific for FTD
      bv. Visuospatial function was preserved except in CBDS/PSP. The clinical
      diagnosis showed a positive predictive value of 87% against autopsy in 67
      patients. Multiple syndromes increase the likelihood of FTD pathology. In
      conclusion, the clinical associations follow the tau-negative and tau-positive
      pathologic dichotomy to some extent, but there is too much overlap to consider
      the clinical groups or their associations separate diseases.

PMID- 17545743
TI  - Memantine for behavioral disturbances in frontotemporal dementia: a case series.
AB  - BACKGROUND: Frontotemporal dementia (FTD) is one of the more common presenile
      dementias. Unlike Alzheimer disease, there are no approved medications to treat
      this debilitating condition. OBJECTIVE: To report the response of memantine on
      the behavioral manifestations of FTD. DESIGN: Case series of 3 patients diagnosed
      with FTD and treated with memantine. RESULTS: All 3 patients showed an
      improvement in total Neuropsychiatric Inventory score with specific improvements
      in the subscale scores of apathy, agitation, and anxiety. Memantine was well
      tolerated in all patients. CONCLUSIONS: This small case series supports the
      notion that memantine may have a beneficial effect on the neuropsychiatric
      symptoms of FTD and should be further studied in a prospective clinical trial.

PMID- 17545744
TI  - Metabolic syndrome and cognitive disorders: is the sum greater than its parts?
AB  - Given the anticipated exponential increase in both the incidence and prevalence
      of dementia, it is critical to identify preventative strategies and improved
      treatments for this disorder. The metabolic syndrome is comprised of 5
      cardiovascular risk factors that include abdominal obesity, hypertriglyceridemia,
      low high-density lipoprotein levels, hypertension, and hyperglycemia. The
      prevalence of the metabolic syndrome, similar to that for cognitive disorders,
      increases dramatically with age. Several possible mechanisms may explain an
      association between the metabolic syndrome and cognitive decline including
      microvascular and macrovascular disease, inflammation, adiposity, and insulin
      resistance. Although some of the individual components of the metabolic syndrome
      have been linked to risk of developing dementia and cognitive impairment, few
      studies have looked at the components of the metabolic syndrome as a whole. We
      found, in 3 separate studies involving elders of different ethnicities, that the
      metabolic syndrome is a risk factor for accelerated cognitive aging. This was
      especially true for elders with the metabolic syndrome and with elevated serum
      level of inflammation. If metabolic syndrome is associated with increased risk of
      developing cognitive impairment, regardless of mechanism, then early
      identification and treatment of these individuals might offer avenues for disease
      course modification.

PMID- 17545745
TI  - Assessment of quality of life as outcome in dementia and MCI intervention trials:
      a systematic review.
AB  - We conducted a systematic review of the use of quality of life (QoL) measures as
      outcome in pharmacological and nonpharmacologic intervention trials in patients
      with Mild Cognitive Impairment or dementia, and their proxies. Randomized
      controlled trials (RCTs) were identified from a search of the Specialized
      Register of the Cochrane Dementia and Cognitive Improvement Group in April 2006.
      We also checked references and systematic reviews. Primary and secondary end
      points were screened for QoL-scales, and it was registered whether information on
      responsiveness was provided. We found 117 pharmacologic and 108 nonpharmacologic
      RCTs. One of the pharmacologic and 4 of the nonpharmacologic studies used QoL as
      primary outcome, and 2 and 3, respectively, as secondary end point. Altogether
      QoL was assessed in only 10 (4.4%) of these RCTs, of which 2 reported on
      responsiveness of QoL. This review provides evidence that QoL-instruments are
      seldom used as outcome measures in RCTs in dementia and Mild Cognitive
      Impairment, and that information on responsiveness is scarce. QoL-measures should
      be applied more often in clinical trials, as currently no disease modifying drugs
      are available, although there are valid and reliable QoL-measures for dementia
      that reflect the aims of palliative care and provide transparent information
      about patient's and caregiver's treatment benefits. We recommend further research
      efforts aimed at the determination of the minimal important difference in QoL
      scales and the responsiveness of QoL-scales. Subsequently, QoL should be measured
      as relevant end point, both in patients and their proxies, in all clinical trials
      in dementia.

PMID- 17545746
TI  - Nerve growth factor gene therapy in Alzheimer disease.
AB  - Nervous system growth factors potently stimulate cell function and prevent
      neuronal death. These broad effects on survival and function arise from direct
      downstream activation of antiapoptotic pathways, inhibition of proapoptotic
      pathways, and stimulation of functionally important cellular mechanisms including
      ERK/MAP kinase and CREB. Thus, as a class, growth factors offer the potential to
      treat neurodegenerative disorders for the first time by preventing neuronal
      degeneration rather than compensating for cell loss after it has occurred.
      Different growth factors affect distinct and specific populations of neurons: the
      first nervous system growth factor identified, nerve growth factor, potentially
      stimulates the survival and function of basal forebrain cholinergic neurons,
      suggesting that nerve growth factor could be a means for reducing the cholinergic
      component of cell degeneration in Alzheimer disease. This review will discuss the
      transition of growth factors from preclinical studies to human clinical trials in
      Alzheimer disease. The implementation of clinical testing of growth factor
      therapy for neurologic disease has been constrained by the dual need to achieve
      adequate concentrations of these proteins in specific brain regions containing
      degenerating neurons, and preventing growth factor spread to nontargeted regions
      to avoid adverse effects. Gene therapy is one of a limited number of potential
      methods for achieving these requirements.

PMID- 17545747
TI  - Combination of olanzapine with opioid-agonists in the treatment of heroin
      addicted patients affected by comorbid schizophrenia spectrum disorders.
AB  - The objective of this study was to evaluate the efficacy of olanzapine (OLA) in
      heroin-dependent patients affected by comorbid schizophrenia spectrum disorders
      (SSD). Sixty-one patients who met the Diagnostic and Statistical Manual of Mental
      Disorders, Fourth Edition criteria for heroin dependence and the criteria for SSD
      (schizophrenia and schizotypal and schizoaffective-bipolar disorders) were
      treated in a 12-week prospective observational trial of substitution treatment in
      combination with OLA or typical antipsychotic haloperidol. Patients were included
      into 2 subgroups, in relationship with treatment, for the evaluation of the end
      points at week 12: group 1, SSD treated with OLA (35 patients); group 2, SSD
      treated with haloperidol (26 patients). Efficacy measures were retention in
      treatment, Symptoms Checklist-90 score changes, negative urinalyses results, and
      craving reduction. The rate of patients who remained in treatment at week 12 in
      group 1 SSD, treated with OLA, was significantly higher (32[91.4%]) than that of
      group 2 SSD (13 [50%]), treated with the typical antipsychotic (P < 0.001). The
      decrease in Symptoms Checklist-90 total scores from baseline, as expression of an
      improvement in comorbid psychopathology in the patients who completed the
      treatment, was significantly more consistent in group 1 than in group 2 patients
      (P < 0.01). Among the patients who remained in treatment, 64.4% achieved early
      full substance abuse remission, whereas 35.6% achieved partial substance abuse
      remission, with a significant difference between 1 (78.13%) and 2 (46.1%)
      treatment subgroups (P = 0.04). Although obtained by an observational-open
      clinical study with multiple limitations, our findings suggest that OLA may be
      able to increase retention and negative urinalyses rates during opioid agonist
      maintenance treatment in the patients with SSD and to improve psychopathology
      symptoms and tolerability in these dually diagnosed heroin addicts. Preliminary
      accurate diagnostic assessment and appropriate psychoactive medication in
      addicted patients affected by schizophrenia and schizotypal and schizoaffective
      bipolar disorders seem to obtain less adverse effects and a more successful
      outcome of drug dependence treatment.

PMID- 17545748
TI  - An open-label, flexible-dose study of memantine in major depressive disorder.
AB  - OBJECTIVE: To assess the efficacy and safety of flexible-dose memantine in
      patients with major depressive disorder (MDD). METHODS: In this 12-week, single
      center, open-label study, 8 patients with MDD were titrated for 4 weeks to 20
      mg/d memantine. Nonresponsive patients were titrated to 30 mg/d (at week 8) or 40
      mg/d (at week 10), provided that no dose-limiting adverse events were observed.
      Outcome measures were the Montgomery-Asberg Depression Rating Scale (MADRS), the
      Hamilton Depression Rating Scale, the Clinical Global Impression-Severity of
      Illness and the Clinical Global Impression-Improvement Scales, the Patient Global
      Evaluation, and the Diagnostic and Statistical Manual of Mental Disorders, Fourth
      Edition, Major Depressive Episode Checklist. Tolerability and safety assessments
      were performed throughout the trial. RESULTS: The safety population comprised 8
      outpatients with a mean (SD) baseline MADRS score of 31.9 (4.45), indicative of
      severe depression. Seven subjects completed the study. All patients attained the
      target dose of 20 mg/d; 3 patients were titrated to 30 mg/d after week 8, and 2
      patients were titrated to 40 mg/d after week 10. The mean dosage across all weeks
      was 18.1 mg. Patients improved on all efficacy measures within 1 week of
      treatment initiation. The mean improvement peaked at week 8 and was maintained
      through week 12 (MADRS, 18.5 [10.3]; last-observation-carried-forward). All
      memantine doses were well tolerated. CONCLUSIONS: Memantine demonstrated early
      onset efficacy in patients with MDD. The treatment was well tolerated. This study
      suggests that double-blind, placebo-controlled studies of memantine in depression
      are merited.

PMID- 17545749
TI  - Transient decrease in serum albumin concentrations in epileptic children treated
      with sodium valproate monotherapy.
AB  - OBJECTIVE: Hypoalbuminemia has been reported in patients with severe disability
      and epilepsy and in patients with epilepsy treated with short-term sodium
      valproate (VPA) therapy; however, serum albumin concentrations have not
      previously been determined in otherwise healthy patients with epilepsy and
      receiving long-term VPA monotherapy. METHODS: Serum albumin concentrations were
      determined in 26 ambulatory children with epilepsy before and at 6, 12, and 24
      months of VPA monotherapy. Serum total protein concentrations and serum
      concentrations of other biochemical markers of liver and renal function such as
      alanine aminotransferase, aspartate aminotransferase, gamma-glutamyltransferase,
      and creatinine concentration were also measured in the study participants before
      and at 6, 12, and 24 months of treatment. RESULTS: Serum albumin concentrations
      were reduced at 6 months of treatment (P = 0.007). Serum alanine aminotransferase
      concentrations were significantly increased at 6 (P = 0.034) and 12 months of
      treatment (P = 0.046), whereas serum aspartate aminotransferase concentrations
      were significantly increased at 6 (P = 0.002) and 12 months of treatment (P =
      0.002). There were no significant correlations between serum albumin and the
      other parameters at 6 months of treatment. CONCLUSIONS: Ambulatory children who
      receive VPA monotherapy may have early but transient decrease in serum albumin
      concentrations. Further studies are needed to address this issue and to determine
      the possible clinical implications and the mechanisms involved in VPA-mediated
      decrease in serum albumin concentrations.

PMID- 17545750
TI  - Monamine oxidase inhibitors: current and emerging agents for Parkinson disease.
AB  - Monoamine oxidase type B (MAO-B) is the predominant isoform responsible for the
      metabolic breakdown of dopamine in the brain. Selective inhibition of brain MAO-B
      results in elevation of synaptosomal dopamine concentrations. Data have been
      reported regarding the selective MAO-B inhibitors, rasagiline and selegiline, for
      the symptomatic treatment of Parkinson disease (PD). Selegiline has demonstrated
      efficacy as monotherapy in patients with early PD (Deprenyl and Tocopherol
      Antioxidative Therapy of Parkinsonism study), but evidence of selegiline efficacy
      as adjunctive treatment in levodopa-treated PD patients with motor fluctuations
      is equivocal. A new formulation of selegiline (Zydis selegiline) has been
      evaluated in 2 small, placebo-controlled studies as adjunctive therapy to
      levodopa. The Zydis formulation allows pregastric absorption of selegiline,
      minimizing first-pass metabolism, and thereby increasing selegiline
      bioavailability and reducing the concentration of amphetamine metabolites.
      Rasagiline is a selective, second-generation, irreversible MAO-B inhibitor, with
      at least 5 times the potency of selegiline in vitro and in animal models.
      Rasagiline has demonstrated efficacy in 1 large, randomized, double-blind,
      placebo-controlled trial (TVP-1012 in Early Monotherapy for Parkinson's Disease
      Outpatients) as initial monotherapy in patients with early PD, and in 2 large,
      controlled trials (Parkinson's Rasagiline: Efficacy and Safety in the Treatment
      of "Off," Lasting Effect in Adjunct Therapy With Rasagiline Given Once Daily) as
      adjunctive treatment in levodopa-treated PD patients with motor fluctuations.
      Unlike selegiline, rasagiline is an aminoindan derivative with no amphetamine
      metabolites. A randomized clinical trial is underway to confirm preclinical and
      preliminary clinical data suggesting rasagiline has disease-modifying effects.

PMID- 17545751
TI  - Oral cholinesterase inhibitor add-on therapy for cognitive enhancement in
      schizophrenia: a quantitative systematic review, Part I.
AB  - RATIONALE: Cognitive impairment in schizophrenia is associated with outcomes
      affecting social function and vocational performance. Cognitive enhancement is
      thus recognized as fundamental in the treatment of schizophrenia. Some clinical
      trials have used acetylcholinesterase inhibitors (AChEIs) add-on therapy to test
      the cognitive-enhancing effects of these kinds of medication, which is usually
      prescribed for indications other than schizophrenia. OBJECTIVE: To perform a
      quantitative systematic review of the effects of AChEI on various cognitive
      domains (attention, language, and motor and executive functions) in
      schizophrenia. DATA SOURCE: Exhaustive electronic search engines, hand searches,
      cross-referencing of studies, and contacts with investigators were carried out.
      DATA SELECTION: The studies included compared neurocognitive performance in
      patients with schizophrenia before and after AChEI treatment in randomized
      controlled trials and crossover and open trials of AChEI in people with
      schizophrenia. RESULTS: Our findings reveal a small, but significant, homogeneous
      effect estimate of AChEI on attention before and after treatment. A small
      nonsignificant heterogeneous effect estimate was yielded for motor performance
      after AChEI treatment. However, no significant change appears in language
      performance or executive functions after AChEI treatment, independently of the
      type of AChEI. After AChEI treatment, when patients were compared with control
      groups, no difference appears in attention and executive functions. Nevertheless,
      the analysis reveals that the control groups performed better on language tasks
      than patients after AChEI treatment but worse on motor tasks. CONCLUSIONS:
      Despite an extensive investigation of the electronic and gray literature, few
      data appropriate for the meta-analysis were found. The results reveal a small
      improvement in attention and a trend on motor tasks after AChEI medication in
      schizophrenia. No clear conclusion can yet be reached concerning the cognitive
      enhancing effects of AChEI considering the small number of studies available.
      This finding needs to be substantiated by larger trials. This systematic review
      complements a meta-analysis focusing on memory, which showed a small improvement
      with a cocktail of antipsychotics and AChEIs.

PMID- 17545752
TI  - Successful treatment of trigeminal neuralgia with milnacipran.
AB  - Paroxysmal pain in a 64-year-old woman diagnosed with trigeminal neuralgia
      disappeared with the administration of carbamazepine, but carbamazepine had to be
      discontinued because of intolerable lassitude and liver dysfunction. Afterward,
      the paroxysmal pain reoccurred, and depressive symptoms appeared. Milnacipran was
      then administered at a dosage of 50 mg/d for 2 months, and the paroxysmal pain
      and depression disappeared completely. Carbamazepine is the drug of first choice
      for trigeminal neuralgia, but the present results suggest that milnacipran is
      worth investigating for patients who do not respond to carbamazepine, who cannot
      stay on carbamazepine because of side effects, and who exhibit depressive
      symptoms.

PMID- 17545753
TI  - Refractory hiccup: successful treatment with gabapentin.
AB  - OBJECTIVE: To report a patient with intractable hiccup which improved with
      gabapentin. CASE REPORT: A 69-year-old woman diagnosed with refractory hiccup
      that started 50 years before improved dramatically after a trial of gabapentin
      for essential tremor. Gabapentin withdrawal led to reappearance of hiccup, which
      improved again after its reintroduction. CONCLUSIONS: Gabapentin should be
      considered as a possible therapy for refractory hiccup.

PMID- 17545754
TI  - Papers presented at the 2006 Meeting of the Musculoskeletal Tumor Society.

PMID- 17545755
TI  - On the treatment of cystic myelogenous sarcoma (myeloid, giant cell sarcoma) with
      curettage instead of amputation. 1889.

PMID- 17545756
TI  - SH3BP2 is rarely mutated in exon 9 in giant cell lesions outside cherubism.
AB  - Giant cell tumor of bone and giant cell reparative granuloma are benign lesions
      with prominent giant (multinucleated) cells, and an understanding of the
      molecular biology and genetics of these lesions will likely aid in more effective
      treatment. Cherubism is a benign lesion of the maxilla and mandible
      histologically similar to giant cell tumor of bone and giant cell reparative
      granuloma. Germline mutations in exon 9 of the gene encoding Src homology 3
      binding protein 2 (SH3BP2) occur in most patients with cherubism. We therefore
      hypothesized SH3BP2 and its putative downstream effector nuclear factor of
      activated T cells c1 isoform (NFATc1) are highly expressed in sporadic
      nonsyndromic giant cell lesions and associated with somatic SH3BP2 mutations. We
      analyzed giant cell lesions for SH3BP2 and NFATc1 expression by RNA blot and/or
      immunohistochemistry and for exon 9 SH3BP2 mutations. We found the SH3BP2
      transcripts and protein were abundantly expressed in giant cell tumors of bone,
      as well as NFATc1 protein. Sequencing of exon 9 of SH3BP2 was normal in all
      sporadic nonsyndromic giant cell lesions. Although many multinucleated giant cell
      lesions of bone share histologic features, the primary genetic defect in
      cherubism and these other giant cell lesions appears different.

PMID- 17545757
TI  - Errors in the MRI evaluation of musculoskeletal tumors and tumorlike lesions.
AB  - Interpretation of an MRI of a suspected musculoskeletal neoplasm can be extremely
      difficult. Fifty-six MRIs originally evaluated by outside radiologists were
      independently evaluated by an expert panel consisting of three specialized
      musculoskeletal radiologists. The outside reports were then graded based upon
      accuracy and completeness of the differential diagnosis. We compared the expert
      opinions with those of the outside radiologists. According to the expert panel,
      only 30 of the 56 (54%) outside reports listed the most likely diagnosis as such
      and only 35 (63%) listed it at all. A complete appropriate differential diagnosis
      was listed in only 22 (39%) of the outside reports. Furthermore, 18 (32%) of the
      outside reports listed diagnoses judged to be extremely unlikely by the experts.
      In a subset of 15 patients with images that the expert panel had judged
      diagnostic of specific entities, only nine of the outside reports listed the
      correct diagnosis as such and only 10 listed it at all. Furthermore, 11 (73%) of
      the outside reports listed extremely unlikely possibilities for these diagnostic
      images. We found a substantial difference between the expert and the outside
      opinions.

PMID- 17545758
TI  - Effect of chemotherapy on initial compressive osseointegration of tumor
      endoprostheses.
AB  - Chemotherapy has long been suspected of having an adverse effect on bone healing.
      Massive tumor endoprostheses which achieve osseointegration via compressive force
      provide a unique model to study the effects of chemotherapy on bone healing. We
      compared distal femoral bone hypertrophy in patients who received chemotherapy
      with those who did not. Fifty four patients underwent distal femoral
      reconstruction with a compression implant. Thirty patients received chemotherapy
      (Group 1), and 24 did not (Group 2). The group of patients receiving chemotherapy
      was younger, had lower body mass indices, and had different diagnoses compared to
      the group of patients not receiving chemotherapy. We used a standardized
      technique to measure bone growth at the bone-prosthetic interface. The rate of
      cortical width increase at the bone-prosthetic junction was faster in Group 2
      compared to Group 1. Similarly, the increase in cortical width from immediate
      postop to 3 months and 6 months postop was greater in Group 2 when compared to
      Group 1. The data suggest chemotherapy administration for musculoskeletal
      malignancy has a substantial initial adverse effect on bone hypertrophy and a
      trend towards reduced prosthetic survival. These findings have important
      implications for the patients with musculoskeletal tumors.

PMID- 17545759
TI  - Experience with cemented large segment endoprostheses for tumors.
AB  - Published reports dealing with tumor prosthesis have yet to establish a clear
      advantage of using either cemented or cementless implants. We examined the
      outcome and complications with modular cemented implants in 135 patients
      identified from our database to strengthen the argument for routine use of
      cemented constructs. The minimum followup was 1.4 months (mean, 57 months;
      median, 47 months; range, 1.4-157 months). The majority of patients (104) had
      sarcoma. The complications included: 11 infections, three of which underwent
      amputation and one a stem revision; eight local recurrences, five of which
      underwent amputation; three hip dislocations; and three incidents of shoulder
      instability. One periprosthetic femur fracture was stabilized operatively. There
      was no aseptic loosening or stem fracture. The 5-year survival rates for distal
      femoral and proximal humeral replacements were 84% and 70%; the 10-year survival
      rates were 79% and 59%. The 5-year survival rates for proximal femur and proximal
      tibia replacements were 78% and 37%. Average Musculoskeletal Tumor Society 1987
      scores and Toronto Extremity Salvage Scores were 21.5 and 73% for proximal femur,
      28.1 and 67% for distal femur, and 21 and 78% for proximal humerus. The survival
      of the endoprostheses related to site of bone resection. Cemented constructs of
      modern design in the context of tumor surgery provide good short-term results.

PMID- 17545760
TI  - Bipolar proximal femoral replacement prostheses for musculoskeletal neoplasms.
AB  - While bipolar proximal femoral replacement prostheses (PFRP) have become a common
      treatment for tumors of the proximal femur, long-term results are not specified
      in the literature. The objective was to determine the complication and revision
      rates of bipolar PFRP and compare them to historical controls of bipolar
      hemiarthroplasties for nontumor indications. Information was retrospectively
      collected on 62 patients who received bipolar PFRP with cemented diaphyseal stems
      for primary or metastatic disease of the proximal femur from 1981 to 2003. Mean
      followup was 5 years. Twelve of 62 (19%) bipolar PFRPs underwent revision.
      Aseptic loosening was the most common complication with six (10%) undergoing
      revision. None were converted to THA due to acetabular erosion. Three patients
      (5%) had problems with dislocation and three (5%) had deep infections. Mean MSTS
      functional rating was 71% of normal function. The limb salvage rate was 98% and
      the 5-year event-free prosthetic survival was 79%. Bipolar PFRPs were found to
      have higher revision, dislocation, and deep infection rates compared to bipolar
      hemiarthroplasty for nontumor indications, but a lower rate of conversion to THA
      due to acetabular erosion. Bipolar PFRPs have good long-term durability with some
      complications, but are able to preserve the limb and provide good function for
      patients.

PMID- 17545761
TI  - Method for the physical analysis of drug-bone cement composite.
AB  - Skeletal metastases are often complicated by progression to impending or
      pathologic fracture and fixation with polymethylmethacrylate (PMMA) bone cement
      is used for stabilization and pain relief. Adjuvant therapy involving the
      delivery of PMMA composites mixed with antibiotic or chemotherapeutic agents
      requires an understanding of the rate of drug diffusion from the cement in
      addition to measurement of its mechanical properties pre- and postelution of
      drug. We have developed a method for the analysis of drug diffusion rate and
      mechanical properties of drug-cement composites using PMMA/methotrexate as a
      model system. The analysis method revealed the addition of methotrexate to PMMA
      in concentrations of 1.8 g methotrexate per 40 g PMMA did not change the
      compression modulus of the cement pre- or postelution of drug. The
      PMMA/methotrexate composites displayed an average diffusion rate of 50
      ng/(mm2)(hour) during the first 6 hours, which decreased to 10 ng/(mm2)(hour) by
      36 hours. Diffusion modeling predicts the 20 x 13-mm cylindrical
      PMMA/methotrexate samples used by the method deliver 10% of the total
      methotrexate content within 80 hours and 25% of the total within 133 days.

PMID- 17545762
TI  - The effect of simulated metastatic lytic lesions on proximal femoral strength.
AB  - Metastatic lesions in the proximal femur can reduce hip strength and lead to
      pathologic fracture. However, current methods for identifying patients at risk of
      pathologic fracture are inadequate. We hypothesized the percentage of intact
      proximal femoral strength remaining after formation of a simulated lytic defect
      within the femoral neck or at the level of the lesser trochanter depends on
      defect location within the respective region. Computed tomography scan-based
      finite element models of 12 cadaveric proximal femora were used to evaluate the
      effect of 20-mm-diameter spherical voids at various locations in the neck and at
      the level of the lesser trochanter. In both regions, the percentage of intact
      strength remaining depended on defect location (p < 0.001). In the neck, the
      strength of specimens with inferomedial defects (median, 50.4% of intact; range,
      27.8-71.7%) was less than the strength of specimens with defects located in the
      center of the neck, superolaterally, or anteriorly (p < 0.05). Near the lesser
      trochanter, anteromedial defects resulted in the lowest strength (median, 66.6%
      of intact; range, 49.2-73.8%). Other defects at the level of the lesser
      trochanter had a markedly smaller effect. These findings may be helpful for
      evaluating pathologic fracture risk.

PMID- 17545763
TI  - Endoscopic resection of symptomatic osteochondroma of the distal femur.
AB  - The surgical risk and complication rates for an open excision of a benign
      osteochondroma have been reported as high as 13%. The advent of minimally
      invasive techniques allows a surgical resection with a smaller incision and a
      potential for less postoperative morbidity. We presumed endoscopic resection of
      symptomatic osteochondroma of the distal femur would decrease postoperative
      morbidity of open surgery and improve functional outcome. We performed endoscopic
      resection of a symptomatic osteochondroma in seven patients among 24 who had
      surgical excision. Preoperative studies include radiographs and computed
      tomography scans. At a mean followup of 33 months, patients were functionally
      evaluated according to the Lysholm score and the International Knee Documentation
      Committee scale. Four exostoses were located at the anterolateral femoral cortex,
      one at the trochlea, and two at the anteromedial cortex. Histologic diagnosis of
      an osteochondroma was confirmed in all cases. The average Lysholm score improved
      22 points from a mean of 74 preoperatively to 96 postoperatively, and according
      to the International Knee Documentation Committee scale, all patients showed a
      normal knee. In 7 of 24 patients with a symptomatic osteochondroma of the distal
      femur close to the knee, we performed endoscopic resection with low morbidity and
      prompt functional recovery.

PMID- 17545764
TI  - Low-intensity pulsed ultrasound does not enhance distraction callus in a rabbit
      model.
AB  - Low-intensity pulsed ultrasound has been reported to have a positive effect when
      applied during the consolidation phase of distraction osteogenesis and bone
      transportation, but the optimal application time has not been determined. We used
      a rabbit model to determine whether low-intensity pulsed ultrasound applied
      during the distraction and early consolidation phases of tibial lengthening would
      have a positive effect on regenerated bone formation. Radiographic analysis
      showed no differences in regenerated callus area or in percent of callus
      mineralization between treated and control tibias immediately after distraction
      or at 1, 2, or 3 weeks after distraction. Similarly, we observed no differences
      in structural stiffness or maximal torque to failure at 1.5 or 3 weeks after
      distraction. We detected no differences in bone mineral appositional rates or
      percent tissue composition measured histologically between groups. Our data do
      not support the application of low-intensity pulsed ultrasound to regenerated
      bone during distraction osteogenesis.

PMID- 17545765
TI  - The 2007 ABJS Nicolas Andry Award: three decades of clinical, basic, and applied
      research on thromboembolic disease after THA: rationale and clinical results of a
      multimodal prophylaxis protocol.
AB  - Total hip arthroplasty is an operation with a high risk for venous
      thromboembolism. Three decades of research conducted at the Hospital for Special
      Surgery identified the exact timing of the thrombogenic stimulus during surgery,
      defined the role of magnetic resonance venography, and established the role of
      certain genetic and acquired predispositions. Based on these studies, we
      implemented a multimodal prophylaxis consisting of a series of safe preventive
      measures applied before, during, and immediately after surgery to reduce the risk
      of venous thromboembolism. If these safe preventive measures are strictly
      observed, postoperative pharmacologic prophylaxis does not need to be aggressive
      in the patient without predisposing factors who mobilizes promptly, thus
      diminishing the risk of bleeding associated with the use of anticoagulants and
      the overall cost of care. Our clinical experience with more than 5000 total hip
      arthroplasties performed during the last decade and closely followed
      prospectively for a minimum of 3 months clearly shows this multimodal prophylaxis
      is safe and effective resulting in a very low prevalence of thromboembolism.

PMID- 17545766
TI  - 50 years ago in CORR: some effects of x-rays on bone by Helen Quincy Woodard,
      PhD; and the long-range effects of radiation on bone by L. Henry Garland, MB.

PMID- 17545768
TI  - Bibliography. Current world literature. Inflammatory bowel disease.

PMID- 17545770
TI  - Immunopathogenesis of inflammatory bowel disease: current concepts.
AB  - PURPOSE OF REVIEW: According to the current paradigm, ulcerative colitis and
      Crohn's disease occur in genetically predisposed individuals because of
      dysregulated immune responses against intraluminal bacterial antigens. Data have
      recently accumulated supporting alternative hypotheses for the pathogenesis of
      inflammatory bowel disease. Here, we present novel immunogenetic pathways and
      discuss their impact on traditional understanding of inflammatory bowel disease.
      RECENT FINDINGS: In the gastrointestinal tract the innate immune system contains
      intraluminal bacteria locally, avoiding invasion of the deeper layers and
      preventing induction of long-standing proinflammatory responses. Failure of this
      protective function of the innate immune system appears to be the primary defect
      in inflammatory bowel disease, as a result of impairment of NOD2 signaling or
      other unidentified deficiencies. The adaptive immune response that ensues was
      thought to be strictly differentiated between T-helper-1 mediated in Crohn's
      disease and T-helper-2 mediated in ulcerative colitis. This concept is rapidly
      changing, however, in light of recent evidence suggesting that tissue injury in
      inflammatory bowel disease is mediated by novel effector pathways, the most
      prominent of which is the interleukin-23/Th17 axis. SUMMARY: Elucidation of the
      pathways that underlie chronic intestinal inflammation will facilitate the
      development of new treatments with increased specificity and probably with
      decreased toxicity.

PMID- 17545771
TI  - Defensins and other antimicrobial peptides in inflammatory bowel disease.
AB  - PURPOSE OF REVIEW: Recently published studies presenting novel and relevant
      information on defensins and other antimicrobial peptides in Crohn's disease and
      ulcerative colitis are reviewed. RECENT FINDINGS: Different clinical
      localizations of Crohn's disease are associated with different deficiencies in
      epithelial and leukocyte antimicrobial peptide expression. As compared with
      ulcerative colitis, Crohn's disease of the colon is characterized by an impaired
      induction of beta defensins, and antimicrobial antiproteases elafin and SLPI, as
      well as the cathelicidin LL37. The attenuated induction of beta defensins is
      linked to fewer gene copy numbers in this locus, which is associated with colonic
      but not ileal Crohn's disease. In contrast, ileal Crohn's disease patients are
      characterized by a reduced antibacterial activity and a specific reduction of
      ileal Paneth cell defensins. This decrease is independent of the grade of
      histological inflammation and cannot be found in inflammation controls. Thus,
      some of these defects can be explained either by direct or indirect genetic
      mechanisms and appear to be primary. SUMMARY: Unlike ulcerative colitis, ileal
      and colonic Crohn's disease are characterized by localized deficiencies of
      antibacterial peptides. Understanding the precise molecular mechanisms of the
      defective antibacterial barrier function might provide new therapeutic
      directions.

PMID- 17545772
TI  - Altered permeability in inflammatory bowel disease: pathophysiology and clinical
      implications.
AB  - PURPOSE OF REVIEW: To present the mechanisms behind barrier disturbance in
      inflammatory bowel disease and their functional consequences. RECENT FINDINGS: A
      reduction in tight junction strands, strand breaks and alteration of tight
      junction protein content and composition characterize Crohn's disease. In
      ulcerative colitis, epithelial leaks appear early as a result of microerosions,
      upregulated epithelial apoptosis and tight junction protein changes with
      pronounced increases in claudin-2. T-helper type 1 cytokine effects by interferon
      gamma and tumour necrosis factor alpha are important for epithelial damage in
      Crohn's disease. Interleukin-13 is the key effector cytokine in ulcerative
      colitis, stimulating epithelial cell apoptosis, and can upregulate claudin-2
      expression. Together with interleukin-13-induced epithelial restitution arrest,
      this may explain why ulcer lesions occur in early stages of ulcerative colitis
      but are only observed in advanced inflammatory stages in Crohn's disease.
      SUMMARY: Barrier dysfunction in inflammatory bowel disease contributes to
      diarrhea by a leak flux mechanism and can cause mucosal inflammation secondary to
      luminal antigen uptake. Barrier abnormalities, such as epithelial tight junction
      changes and apoptotic leaks, gross mucosal lesions, and epithelial restitution
      arrest are responsible for these abnormalities and are the result of immune
      dysregulation. Studying the underlying mechanisms is important in understanding
      the pathophysiology of inflammatory bowel disease and developing therapeutic
      strategies.

PMID- 17545773
TI  - Inflammation and the mucosal microcirculation in inflammatory bowel disease: the
      ebb and flow.
AB  - PURPOSE OF REVIEW: Inflammatory bowel disease pathogenesis involves the interplay
      of multiple biological factors, among which nonimmune cells, including the
      endothelium, represent a crucial component of disease pathogenesis. RECENT
      FINDINGS: Endothelial cells play a key role in chronic inflammation through
      multiple and disparate activities. The mucosal microvasculature in inflammatory
      bowel disease is dysfunctional, overexpresses inflammatory molecules and
      undergoes intense angiogenesis, failing to exert its physiological
      antiinflammatory and anticoagulant activities. SUMMARY: The mucosal
      microcirculation is abnormal in inflammatory bowel disease and represents a novel
      component of disease pathogenesis; targeting the various abnormalities of the
      inflammatory bowel disease microcirculation may lead to new forms of therapeutic
      intervention.

PMID- 17545774
TI  - Inflammatory bowel disease diagnosis, evaluation and classification: state-of-the
      art approach.
AB  - PURPOSE OF REVIEW: Progress in inflammatory bowel disease, aided by use of animal
      models, and focused on pathways leading to inflammation and the relationship
      between the innate and adaptive immune systems, is identifying target pathogenic
      mechanisms for therapeutic intervention. This review will describe the most
      recent advances and discuss promising pathways for therapeutic discovery. RECENT
      FINDINGS: Identification and testing of immune and genetic markers to distinguish
      subgroups of patients with inflammatory bowel disease have surged over the last
      decade. What was limited to a few serum antibodies is now complemented with a
      number of genetic associations. Recent years have seen renewed interest, with
      additional evidence on the relationship between intestinal commensal bacteria and
      the inflammatory process in Inflammatory bowel disease. SUMMARY: There is
      emerging evidence that discriminating pathogenic abnormalities are present in
      certain clusters of patients, defined by selected immune responses. These traits
      have been used to identify correlates between relevant mouse models and
      immunophenotypic clusters of patients. Such approaches will not only help us to
      more easily define groups of patients for study, but will also enhance our
      understanding of the interface between various pathways and disease expression,
      and ultimately, identify the primal therapeutic targets in the appropriate
      subgroups of patients.

PMID- 17545775
TI  - Biological therapies in inflammatory bowel disease: top-down or bottom-up?
AB  - PURPOSE OF REVIEW: Conventional therapeutic algorithms cannot, or only to a
      certain degree, prevent surgery or complications in inflammatory bowel disease.
      The new concept of early aggressive or 'top-down' treatment has evolved from the
      impressive results of new biological agents in the treatment of patients who were
      refractory to standard therapy. New data, suggesting that this strategy may be
      advantageous, has recently been published. RECENT FINDINGS: In uncontrolled
      studies, early administration of azathioprine as well as infliximab has been
      shown to be associated with a prolonged maintenance of remission in Crohn's
      disease patients. The recently presented preliminary data from a controlled study
      comparing early administration of infliximab and azathioprine ('top-down'
      therapy) versus conventional 'step-up' therapy showed superior mucosal healing, a
      more rapid remission and higher remission rates in patients in the top-down
      treatment arm. The ongoing SONIC study, which compares infliximab therapy with
      and without azathioprine, will provide additional information regarding the
      relative importance of both drugs in this respect. SUMMARY: The significance of
      top-down treatment remains to be confirmed in prospective clinical studies aimed
      at high-risk patients. The standard use of this approach cannot be advocated
      presently.

PMID- 17545776
TI  - Nutrition in inflammatory bowel disease.
AB  - PURPOSE OF REVIEW: Nutrition plays a significant role in the pathogenesis and
      treatment of the two major forms of inflammatory bowel disease: Crohn's disease
      and ulcerative colitis. In addition, patients with inflammatory bowel disease are
      often found to have nutrient deficiencies at the time of diagnosis, whereas
      others develop features of malnutrition over the course of their illness.
      Therefore, an understanding of the relationship between nutrients and
      inflammatory bowel disease is important if these patients are to receive optimal
      care. RECENT FINDINGS: Epidemiologic and basic research has helped to shed light
      on the interaction between diet and the pathogenesis of inflammatory bowel
      disease. Numerous clinical trials utilizing various types of lipids, including
      fish oil and short chain fatty acids, suggest that fats play an important role in
      the inflammatory response that characterizes inflammatory bowel disease. Vitamins
      and other micronutrients involved in nutrient metabolism and modulation of
      oxidative stress are also considered in this review. SUMMARY: This update
      discusses nutritional issues that can be used to help prevent and treat nutrient
      deficiencies and ameliorate disease activity in individuals with inflammatory
      bowel disease.

PMID- 17545777
TI  - Challenges and progress in pediatric inflammatory bowel disease.
AB  - PURPOSE OF REVIEW: The induction and maintenance of disease remission and
      prevention of complications are primary goals in the management of inflammatory
      bowel disease. Recent research has added new insights into the pathogenesis,
      epidemiology, and treatment options for children with inflammatory bowel disease,
      and the findings will enable clinicians to develop a more rational approach to
      the diagnosis and treatment of pediatric patients with ulcerative colitis and
      Crohn's disease. RECENT FINDINGS: Population-based studies have confirmed the
      increased incidence of inflammatory bowel disease in children. Previous medical
      history and serologies can be predictive of complications in Crohn's disease.
      Newer radiological and capsule endoscopic modalities have a potential future role
      in the diagnosis and interval assessment of patients with inflammatory bowel
      disease. Biological therapies play an increasingly prominent role in the
      management of children with ulcerative colitis and Crohn's disease. Studies of
      children with inflammatory bowel disease suggest that behavioral interventions
      may have a positive impact on morbidity and overall quality of life. SUMMARY: New
      information concerning the natural history of Crohn's disease and ulcerative
      colitis and a better understanding of different treatment modalities will enable
      the development of increasingly effective and individualized pharmacological
      treatment plans for children with inflammatory bowel disease.

PMID- 17545779
TI  - Recent developments in esophageal motor disorders.
AB  - PURPOSE OF REVIEW: Every year more insight into the pathogenesis and treatment of
      esophageal motor disorders is obtained. This review highlights some interesting
      literature published in this area during the last year. RECENT FINDINGS:
      Longitudinal and circular muscle contractions act in a well coordinated fashion
      to allow normal peristalsis. Techniques such as intraluminal impedance, high
      resolution manometry and intraluminal ultrasound provide useful additional
      information on esophageal function both in the normal and abnormal situation. The
      dynamics of the gastroesophageal junction can be studied with a newly developed
      probe, and the mechanism behind transient lower esophageal sphincter relaxations
      is still being unravelled. New manometric criteria for nutcracker esophagus have
      been proposed, whereas further evidence is reported supporting an association
      between diabetes mellitus and cardiovascular disease and esophageal dysmotility
      and spasm, respectively. Finally, several long-term follow-up results of surgical
      myotomy and pneumodilatation have been reported. SUMMARY: Due to the perfection
      of esophageal measuring techniques, our knowledge of esophageal function
      continues to increase. The studies reviewed here provide interesting information
      on the pathogenesis and treatment of several esophageal motor disorders.

PMID- 17545780
TI  - Diagnosis and therapy of esophageal vascular disorders.
AB  - PURPOSE OF REVIEW: The most relevant studies concerning the diagnosis of
      esophageal varices, primary and secondary prophylaxis and treatment of variceal
      bleeding published in the last year are reported. RECENT FINDINGS: The specific
      areas reviewed are those that refer to studies on the noninvasive or minimally
      invasive diagnosis of the presence of esophageal varices, the prevention of the
      formation and of the progression of varices from small to large, the prevention
      of the first variceal haemorrhage, the treatment of the acute bleeding episode,
      and the prevention of rebleeding. SUMMARY: Relevant studies are reviewed
      regarding the validation of noninvasive indices for the presence of varices, the
      use of the esophageal videocapsule to diagnose varices, the comparison of methods
      to prevent the first variceal haemorrhage, the use of the hepatic vein pressure
      measurement to monitor the haemodynamic response to beta-blockers, the long-term
      protection from bleeding by beta-blockers, the use of a double dose of
      somatostatin to control bleeding, the evaluation of the best endoscopic method to
      treat variceal bleeding in addition to vasoactive drugs, and the identification
      of prognostic factors for early and late mortality after a variceal bleed.

PMID- 17545781
TI  - Developments in pathogenesis and diagnosis of gastroesophageal reflux disease.
AB  - PURPOSE OF REVIEW: Although gastroesophageal reflux is a common disorder,
      diagnosis is still imprecise. Moreover, its pathogenesis is incompletely
      understood. This review summarizes recent progress in diagnosis and our
      understanding of the pathogenesis of gastroesophageal reflux disease. RECENT
      FINDINGS: Recent studies have focused on the pattern of reflux in the distal
      esophagus, just above the esophago-gastric junction, challenging its importance
      on the genesis of reflux symptoms. New techniques, such as impedance, could
      improve the diagnostic yield, especially in patients with nonacid reflux.
      Esophageal sensitivity and motility, transient lower esophageal sphincter
      relaxations, and hiatus hernia are important pathogenic mechanisms of reflux
      disease. Studies showed that obesity plays a role in the pathogenesis of reflux
      symptoms; a disruption of the esophago-gastric junction (leading to hiatus
      hernia) could allow reflux to occur. The association between reflux (particularly
      nonacid) and extraesophageal manifestations of gastroesophageal reflux disease
      has been further evaluated. SUMMARY: Improvement of diagnostic techniques and
      better understanding of the pathogenesis of reflux may lead to new or better
      therapeutic modalities. Our understanding of some of the risk factors for reflux
      has been increased. Extra-esophageal manifestations and their association with
      gastroesophageal reflux are still a very controversial and promising area of
      research.

PMID- 17545782
TI  - Medical therapy of gastroesophageal reflux disease.
AB  - PURPOSE OF REVIEW: Proton pump inhibitors remain the mainstay of medical therapy
      in gastroesophageal reflux disease. Despite their increasing use, up to 40% of
      patients are not fully satisfied with their antireflux therapy. Recent data on
      efficacy and safety are reviewed and causes of failure are discussed. RECENT
      FINDINGS: Several randomized studies and a metaanalysis have shown marginal
      differences in efficacy between various proton pump inhibitor regimens. In
      subgroups, however, such as severe esophagitis, esomeprazole may be superior.
      Poor compliance is one of the main causes of failure. Nonacid reflux is likely to
      play an important role, especially in patients with regurgitation or cough
      persisting on therapy. Genetic polymorphisms involved in proton pump inhibitor
      metabolism, Helicobacter pylori infection or nocturnal acid breakthrough during
      therapy are probably less important than initially suspected. Recent
      pharmacological developments include new proton pump inhibitor isomers, potassium
      competitive acid blockers and inhibitors of transient lower esophageal sphincter
      relaxations. SUMMARY: There are still important unmet needs in the treatment of
      gastroesophageal reflux disease. Optimizing acid control is unlikely to improve
      the condition of the majority of patients with incomplete proton pump inhibitor
      response. Inhibition of transient lower esophageal sphincter relaxations remains
      the major pharmacological target for future drug development.

PMID- 17545783
TI  - Novel findings in the pathogenesis of esophageal columnar metaplasia or Barrett's
      esophagus.
AB  - PURPOSE OF REVIEW: In esophageal metaplasia the transdifferentiation of the
      epithelium is the result of longstanding gastroesophageal reflux disease that
      causes inflammation of the esophageal squamous mucosa, and occasionally is
      followed by replacement of the squamous epithelium by a columnar type of mucosa.
      For a long time, the molecular mechanisms involved in metaplasia were poorly
      understood. This review focuses on several recent findings on the molecular
      mechanisms involved in esophageal columnar metaplasia. RECENT FINDINGS: Our
      recent findings on bone morphogenetic protein 4 and other recent discoveries in
      the field of cell signaling that take place during the sequence of inflammation
      and epithelial transdifferentiation are highlighted. In this process, several
      embryonic pathways that were silenced in the adult esophagus, and factors that
      are normally involved in the homeostasis of the large intestine, seem to be
      induced. These factors may mediate transdifferentiation of the esophageal
      epithelium. SUMMARY: Although there are many aspects that need further
      investigation, it seems that in columnar metaplasia of the esophagus inductive
      morphogenes such as bone morphogenetic protein 4 are important for development
      and differentiation. Development of specialized intestinal type of metaplasia is
      the result of a succession of events, in which the effect of stromal factors is
      followed by expression of intestine-specific factors.

PMID- 17545784
TI  - Nongastroesophageal reflux disease-related infectious, inflammatory and injurious
      disorders of the esophagus.
AB  - PURPOSE OF REVIEW: To review recently published studies presenting novel and
      relevant information on some esophageal infectious, inflammatory and injurious
      diseases. RECENT FINDINGS: In the treatment of Candida esophagitis, fluconazole
      remains the treatment of choice, but clinical failures indicate new therapeutic
      opportunities, like two new echinocandins, micafungin and anidulafungin.
      Eosinophilic esophagitis is an increasingly recognized entity. New therapeutic
      insights come from a six-food elimination diet in children and from fluticasone
      propionate in adults; humanized monoclonal IgG antibody anti-interlukin-5,
      mepolizumab, has been shown to decrease eosinophilia and ameliorate symptoms.
      There has been some advance in microscopic characterization of lymphocytic
      esophagitis. Esophagitis is found to be present in 67% of patients with pemphigo
      vulgaris, in 32.3% of patients with systemic sclerosis and to be associated with
      thoracic neoplasias. In the case of caustic ingestion, endoscopic ultrasound with
      miniprobes has proven not to be better than videoendoscopy. Recent evidence shows
      that systemic steroids might even be harmful. Mitomycin C applied on fresh wounds
      is currently being evaluated. Stenting of the stricture has been proposed for
      contrasting esophageal remodeling. SUMMARY: These recent findings, together with
      a better understanding of diseases such as eosinophilic or lymphocytic
      esophagitis, allow new diagnostic and therapeutic approaches.

PMID- 17545785
TI  - Surgical options and outcomes in Barrett's esophagus.
AB  - PURPOSE OF REVIEW: Barrett's esophagus is a complication of chronic
      gastroesophageal reflux that results in the replacement of normal stratified
      squamous epithelium in the distal esophagus by metaplastic columnar mucosa and it
      carries a 30-fold to 125-fold risk of progression to esophageal adenocarcinoma.
      RECENT FINDINGS: Laparoscopic antireflux surgery has proved durable and effective
      in treating reflux and reflux-related symptoms in patients with Barrett's
      esophagus. Recent studies have also focused on the histological changes induced
      in Barrett's epithelium by antireflux surgery. This article reviews the current
      literature, analysing the impact of antireflux surgery on both the clinical and
      the histopathological outcomes. SUMMARY: Recent studies have disproved the widely
      held assumption that, once established, Barrett's esophagus does not change.
      Antireflux surgery can achieve a regression of intestinal metaplasia to cardiac
      mucosa in patients with Barrett's esophagus and may thus alter the natural
      history of the disease.

PMID- 17545787
TI  - Bibliography. Current world literature. Esophagus.

PMID- 17545786
TI  - Pathogenesis, diagnosis and therapeutic possibilities of esophageal cancer.
AB  - PURPOSE OF REVIEW: This article reviews developments in pathogenesis, diagnosis
      and therapy of esophageal cancer published in 2006. RECENT FINDINGS: Gene
      expression profiles in esophageal adenocarcinoma reveal information on its
      pathogenesis. One study disputed the UK guideline to perform upper endoscopy only
      in the presence of alarm symptoms. Evidence was presented that staging
      investigations for esophageal cancer should preferentially be performed in expert
      centers. Early [F]fluorodeoxyglucose PET was shown to predict response to
      neoadjuvant chemotherapy. A large randomized study demonstrated that peroperative
      chemotherapy improved survival in esophagogastric adenocarcinoma. The current
      American Joint Committee on Cancer staging system probably needs revision in that
      the number of involved lymph nodes and extent of lymphadenectomy should be
      included. Socioeconomic factors are involved in treatment decisions and outcome
      of esophageal cancer. Chemotherapy and chemoradiotherapy are increasingly being
      used in the palliation of esophageal cancer. Palliation of dysphagia with stents
      was disputed as these devices may be associated with a high complication risk and
      may not improve nutritional status. SUMMARY: In 2006, microarray technology was
      introduced to elucidate the pathogenesis of esophageal cancer. In addition,
      refinements in staging of esophageal cancer were proposed. Finally, (chemo
      )radiotherapy is increasingly being used in the neoadjuvant setting and for
      palliation of esophageal cancer.

PMID- 17545790
TI  - Outpatient therapy for febrile neutropenia.
AB  - PURPOSE OF REVIEW: The management of febrile neutropenia has evolved
      significantly with the development of risk stratification and recognition of the
      efficacy of oral antibiotics in low-risk patients. There remains uncertainty
      concerning the need for hospitalization and role of early hospital discharge. We
      review recent evidence in this field and identify outstanding issues for future
      research. RECENT FINDINGS: Studies have confirmed the utility of the MASCC risk
      index. Preliminary findings suggest that early hospital discharge is feasible in
      low-risk patients with solid tumours and lymphomas, at least in specialist
      centres. Median hospital stays may be reduced to 48 h with no increase in serious
      medical complications. Readmission rates remain low. SUMMARY: All patients with
      febrile neutropenia should undergo risk stratification on admission, and low-risk
      patients should be considered eligible for combination oral antibiotics from the
      outset. Those patients who show signs of fever resolution and subjective
      improvement are eligible for early discharge. More research is required with
      regard to patients with haematological malignancies and/or receiving prophylactic
      antibiotics, and in the development of factors predictive of successful early
      discharge. Further data are required regarding whether strategies involving early
      discharge can be safely implemented at centres outside those which have pioneered
      these approaches.

PMID- 17545791
TI  - Granulocyte colony-stimulating factors: finding the right indication.
AB  - PURPOSE OF REVIEW: Neutropenic complications including febrile neutropenia
      represent major dose-limiting toxicities of cancer chemotherapy. Recommendations
      for the use of recombinant myeloid growth factors to reduce the risk of
      neutropenic complications and sustain dose intensity continue to evolve. RECENT
      FINDINGS: Several randomized controlled trials and meta-analyses have confirmed
      that the myeloid growth factors reduce the risk of neutropenic complications and
      may facilitate delivered dose intensity in patients receiving cancer
      chemotherapy. Older age and certain comorbidities significantly increase the risk
      of febrile neutropenia and its consequences. Three new clinical practice
      guidelines for the use of the myeloid growth factors have been published by major
      professional oncology organizations including the American Society of Clinical
      Oncology, the European Organization for Research and Treatment of Cancer and the
      National Comprehensive Cancer Network. The recommendations and evidence basis for
      these guidelines are presented here. All three new or updated guidelines
      recommend prophylactic use of the myeloid growth factors in cancer patients
      receiving chemotherapy at 20% or greater risk of febrile neutropenia and in those
      with important variables that increase individual risk of neutropenic
      complications. SUMMARY: Consistent clinical practice guidelines based on multiple
      randomized control trials and meta-analyses should further guide the appropriate
      and cost-effective use of these agents.

PMID- 17545792
TI  - Management of painful bone metastases.
AB  - PURPOSE OF REVIEW: This review examines recent data on the pathophysiology and
      mechanisms of bone pain; it highlights the use of multiple and interdisciplinary
      treatments rather than sole use of traditional analgesics. RECENT FINDINGS: Bone
      pain has been shown to have a unique pathophysiology. Recent experimental
      (animal) models have revealed that, parallel to increased bone destruction,
      ipsilateral spinal cord segments that receive primary input from the cancerous
      femur exhibit several notable neurochemical changes. These mandate the use of
      opioid doses sufficient to inhibit the observed nociceptive behaviours; these
      doses are greater than those required to alleviate pain behaviours of comparable
      magnitude generated by inflammatory pain. Several substances have been tested in
      this animal model. SUMMARY: According to new preclinical data, treatment of bone
      cancer pain requires multidisciplinary therapies such as radiotherapy applied to
      the painful area along with systemic treatment (hormone therapy or chemotherapy)
      and supportive care (analgesic therapy and bisphosphonates). In some selected
      cases use of radioisotopes and other noninvasive or minimally invasive techniques
      may be useful in the management of metastatic bone pain. The treatment should be
      individualized according to the patient's clinical condition, life expectancy,
      and quality of life.

PMID- 17545793
TI  - Osteonecrosis of the jaw related to the use of bisphosphonates.
AB  - PURPOSE OF REVIEW: Osteonecrosis of the jaw associated with the use of potent
      nitrogen containing bisphosphonates is a new and challenging clinical entity with
      a high impact on quality of life. This review attempts to consolidate the rapidly
      expanding literature into practical guidelines and provides expert consensus for
      areas of uncertainty. RECENT FINDINGS: Diagnostic criteria and a staging system
      for osteonecrosis of the jaw have been proposed, and histomorphologic analysis
      has confirmed osteonecrosis of the jaw as a proper disease, distinctively
      different from osteoradionecrosis. Various guidelines for the management of
      osteonecrosis of the jaw have been suggested and further retrospective research
      has provided new insights into its epidemiology. SUMMARY: Osteonecrosis of the
      jaw is a distinct entity of uncertain origin that is increasingly being observed
      in patients treated with potent aminobisphosphonates, although the etiology is
      probably multifactorial. Recent data confirm the predisposition of multiple
      myeloma patients to develop osteonecrosis of the jaw. Although various treatment
      strategies have been reported, conservative management remains the mainstay of
      therapy.

PMID- 17545794
TI  - Intestinal mucositis: mechanisms and management.
AB  - PURPOSE OF REVIEW: To describe the advances in the rapidly evolving field of
      intestinal (or alimentary) mucositis during the past year. RECENT FINDINGS: Major
      advances have been made in both the clinical and preclinical setting, with the
      publication of a suite of articles regarding the pathobiology and management of
      mucositis, as well as several articles on important basic research in the area.
      The mechanism of mucositis development is now understood to be much more complex
      than previously thought, with an interplay of host and drug factors leading to
      overt damage, and variation in manifestation of that damage depending on the
      specific region of the gut. The MASCC/ISOO management guidelines for mucositis
      have been updated: a recommendation for the use of palifermin in the hematology
      transplant setting has been added, and a couple of previous recommendations have
      been revoked. This marks an important milestone in mucositis, as it is the first
      time a drug has been available that substantially reduces the occurrence and
      severity of mucositis. SUMMARY: There is still much to be done to abolish the
      severe toxicity of chemotherapy and radiotherapy; however, progress is
      accelerating, and new targeted drugs are becoming available.

PMID- 17545795
TI  - Granulocyte colony-stimulating factors in the management of chemotherapy-induced
      neutropenia: evidence based review.
AB  - (1) Neutropenia is a frequent complication of chemotherapy associated with life
      threatening infections, hospitalisation, and chemotherapy dose reductions and
      delays.(2) Primary prophylaxis with granulocyte colony-stimulating factors has
      been shown to reduce the incidence and duration of neutropenia, febrile
      neutropenia, infections, hospitalisation and antibiotic use.(3) Recent randomised
      clinical trials of filgrastim, lenograstim and pegfilgrastim showed variable
      results across patient groups at different risks of febrile neutropenia.(4)
      Pegfilgrastim is at least as effective as filgrastim in the prophylaxis of
      chemotherapy-induced neutropenia and has improved pharmacokinetics requiring
      reduced administration.

PMID- 17545796
TI  - Treatment of patients with advanced soft tissue sarcoma: disappointment or
      challenge?
AB  - PURPOSE OF REVIEW: We give an overview on the emerging compounds for patients
      with soft tissue sarcoma. Included are recent developments in targeted therapy,
      focusing on the following: antiangiogenic and immunomodulatory drugs (e.g. anti
      cytotoxic T lymphocyte associated antigen-4 monoclonal antibody), Bcl-2 antisense
      therapy, raf kinase and mammalian target of rapamycin inhibition, heat shock
      protein modulators, minor groove binders and other agents being developed. RECENT
      FINDINGS: Soft tissue sarcomas are a heterogeneous group of tumours that arise
      predominantly from the embryonic mesoderm. They account for fewer than 1% of all
      adult malignancies. The prognosis of patients with advanced metastatic soft
      tissue sarcoma remains poor, with disease-free survival at 5 years below 10%.
      Complete resection remains the only potentially curative treatment option. Only
      few chemotherapeutic agents have been identified to be active, with reported
      response rates for doxorubicin and ifosfamide of around 20%. New strategies are
      urgently needed to improve outcomes. SUMMARY: Understanding of the molecular
      biology and pathogenesis of soft tissue sarcomas has been enhanced, and in the
      near future this should translate into molecular tumour characterization and
      development of new therapeutic strategies.

PMID- 17545797
TI  - Adjuvant and neoadjuvant combination chemotherapy for osteogenic sarcoma.
AB  - PURPOSE OF REVIEW: The most recent developments regarding chemotherapy treatment
      of osteogenic sarcoma are reviewed, with special emphasis on prospective clinical
      trials and evaluations of late effects of chemotherapy. RECENT FINDINGS: In
      recent years, clinical research has essentially focused on possible refinements
      of the classic four-drug (methotrexate, cisplatin, doxorubicin and ifosfamide)
      therapy rather than investigating new drugs. It has been demonstrated that dose
      intensification does not improve prognosis. Many investigators have evaluated
      late chemotherapy-related side effects, particularly in terms of cardiac, renal
      and auditive toxicity, risk of infertility and of second tumors. Recent findings
      recommend further studies to define the role of the immunostimulating agent
      muramyl tripeptide-phosphatidilethanolamine in osteosarcoma. Preclinical and
      phase II studies suggest an activity of mammalian target of rapamycin (mTOR)
      inhibitors in osteosarcoma, which also deserves further clinical studies.
      SUMMARY: At present, patients with nonmetastatic osteosarcoma of the extremity
      aged less than 40 years have an expected 5-year survival rate of 70% with a
      chemotherapy regimen based on methotrexate, cisplatin, doxorubicin and
      ifosfamide. Further improvement cannot be achieved by dose intensification of
      treatment and new strategies are required. Prolonged follow-up is mandatory due
      to the risk of late effects, second tumors and late relapse from osteosarcoma.

PMID- 17545798
TI  - Hormonal therapy of endometrial stromal sarcoma.
AB  - PURPOSE OF REVIEW: Low-grade endometrial stromal sarcomas are steroid receptor
      positive tumors with slow tumor progression and high recurrence rates, which lack
      established treatment protocols. We present an update on hormonal therapy
      options. RECENT FINDINGS: In the past, hormonal therapy consisted of progestins
      for advanced/recurrent/metastatic low-grade endometrial stromal sarcomas.
      Aromatase inhibitors and gonadotropin-releasing hormone analogues have become new
      effective alternatives for first and second line treatment. The high recurrence
      rates after short disease free intervals in low-grade endometrial stromal sarcoma
      patients were partly due to inadvertent growth stimulation during estrogen
      containing hormone replacement therapy and tamoxifen treatment, which - according
      to current knowledge - are contraindicated. Recently, hormonal therapy has been
      introduced for the prevention of recurrences. Aromatase inhibitors are becoming
      the treatment of choice, since progestins are poorly tolerated due to side
      effects. The effective duration of preventive hormonal therapy is still
      undetermined. SUMMARY: Hormonal therapy with progestins, aromatase inhibitors and
      gonadotropin-releasing hormone analogues has become an effective treatment
      alternative to radiation and chemotherapy for low-grade endometrial stromal
      sarcoma patients. Preventive hormonal therapy is of particular interest in the
      setting of concomitant endometriosis.

PMID- 17545799
TI  - Second line therapies for the treatment of gastrointestinal stromal tumor.
AB  - PURPOSE OF REVIEW: Most gastrointestinal stromal tumors eventually acquire
      resistance to imatinib mesylate. This review focuses on recent progress on
      management of patients whose disease progresses on the standard dose of imatinib.
      RECENT FINDINGS: Approximately 30% of patients failing standard-dose imatinib
      achieve disease stabilization with high-dose imatinib, but objective responses
      are few and the clinical benefit usually short-lived. Patients receiving enzyme
      inducing drugs may need high imatinib doses to achieve therapeutic blood
      concentrations. Surgical excision of a single growing metastasis leads to a
      median progression-free survival time of 7-11 months. Sunitinib malate is
      effective following imatinib failure. The median time to disease progression is
      approximately 6 months with sunitinib therapy versus 6 weeks with placebo
      following discontinuation of imatinib, but few (5%) patients achieve objective
      response. Patients with gastrointestinal stromal tumor with KIT exon 9 mutation
      may benefit more from sunitinib than those with exon 11 mutation. Sunitinib
      frequently causes abnormal thyroid function. SUMMARY: Sunitinib is now the
      approved second line therapy following imatinib failure and for patients
      intolerant to imatinib. The clinical benefit is only moderate, and thyroid
      function monitoring is required. Several investigational agents are being
      evaluated for imatinib-resistant gastrointestinal stromal tumor. Palliative
      procedures, such as hepatic arterial embolization, also require study.

PMID- 17545800
TI  - The role of radiation in retroperitoneal sarcomas: a surgical perspective.
AB  - PURPOSE OF REVIEW: This review focuses on the current concepts relating to the
      use of radiation therapy in the care of surgical patients with retroperitoneal
      sarcoma. Radiation therapy for retroperitoneal sarcoma patients is complex
      because it requires decisions on not only the timing of administration, but also
      the technique of delivery. RECENT STUDIES: Multiple studies have reported
      improved local recurrence-free survival in patients who received adjuvant
      external beam radiation therapy. Recent studies have demonstrated the efficacy of
      more sophisticated delivery methods for radiation therapy to deliver high dose
      rates while sparing surrounding normal tissues. Other recent studies have
      demonstrated the safety and feasibility of preoperative radiation therapy for
      retroperitoneal sarcoma. Preoperative radiation results in decreased local
      recurrence rates and minimal toxicity. The use of intraoperative radiation
      therapy has also been examined as a means to improve local recurrence rates, but
      may be associated with more radiation-related morbidity. SUMMARY: There is good
      evidence that radiation therapy improves local control rates. Preoperative
      external beam radiation therapy may be the preferred sequence to improve tumor
      resectability and local-regional control with less risk of complications.
      Although data suggest that the addition of intraoperative radiation therapy to
      external beam radiation therapy improves local control, intraoperative radiation
      therapy may be related to additional toxicity.

PMID- 17545801
TI  - Chordoma.
AB  - PURPOSE OF REVIEW: To review developments in chordoma treatment. RECENT FINDINGS:
      Recent series with prolonged follow-up show that adequate margins are necessary
      for surgery to be curative. Safe margins are often difficult to obtain due to the
      anatomical sites of chordoma: sacrum, skull base and spine. Tumors in these sites
      are problematic for radiation therapy as well, and this adds to the need for high
      doses. Hadrons have therefore been used in addition to, or instead of, photons.
      New photon beam techniques, e.g. intensity modulated radiation therapy and
      stereotactic procedures, have recently been evaluated. Although less available
      than photons, hadrons possess certain advantages. While chemotherapy is poorly
      active, recent interest has focused on molecular-targeted agents. Imatinib was
      shown to be active, providing mainly nondimensional tissue responses in a
      significant proportion of patients, which may improve symptoms and progression
      free interval. Epidermal growth factor receptor targeting, anti-angiogenics, and
      the combination of targeted agents with chemotherapy and radiation therapy are
      also under scrutiny. SUMMARY: Two major issues about local treatment remain
      unresolved: when to complement surgery with radiation therapy, and how best to
      deliver high doses of radiation therapy to the tumor tissue. Regarding systemic
      treatment, there is ongoing research into how to exploit molecular-targeted
      therapies.

PMID- 17545802
TI  - Update on chondrosarcomas.
AB  - PURPOSE OF REVIEW: This paper reviews recent molecular, biologic, developmental
      therapeutic, and clinical findings in conventional and variant chondrosarcomas.
      RECENT FINDINGS: The prognosis of chondrosarcomas traditionally correlates with
      histologic grade and adequacy of surgery. Newer markers of cell differentiation,
      activation, genetics, and cell signaling may offer important prognostic
      information. Translational research has validated platelet-derived growth factor
      receptor, estrogen signaling, matrix metalloproteinase-1, histone deacetylase,
      methylthioadenosine phosphorylase, and vascular endothelial growth factor-A as
      potential therapeutic targets. Bisphosphonates may also possess important
      antitumoral effects. Molecular studies have established that extraskeletal myxoid
      chondrosarcoma is a unique entity defined by the presence of a fusion gene
      between the orphan nuclear receptor, CHN/NOR1, and a promiscuous partner, most
      commonly EWSR1. Clinical studies have shown that development of second
      malignancies is an uncommon but real risk for chondrosarcoma survivors; the
      benefit of chemotherapy for dedifferentiated chondrosarcomas remains
      questionable; and late recurrences of clear cell chondrosarcomas emphasize the
      need for long-term follow up. SUMMARY: Chondrosarcomas are a heterogeneous group
      of bone and soft tissue tumors. Recent advances in molecular diagnostics,
      pathobiology, and developmental therapeutics will aid both scientists and
      clinicians in improving the classification and therapy of this diverse family of
      cartilaginous tumors.

PMID- 17545803
TI  - Telomere maintenance in sarcomas.
AB  - PURPOSE OF REVIEW: To examine the activation of telomere maintenance in a variety
      of sarcoma subtypes, and to review the consequences of telomere maintenance with
      respect to genome stability and tumor progression. RECENT FINDINGS: A hallmark of
      tumor cells is replicative immortality, which can be achieved, in part, by the
      activation of a telomere maintenance mechanism. A significant proportion of
      tumors show activation of telomerase, a specialized enzyme that adds telomeric
      repeats to pre-existing telomeres. Recent work has demonstrated, however, that a
      telomerase-independent mechanism called ALT (alternative lengthening of
      telomeres) is activated as frequently as telomerase in a variety of tumor types,
      particularly those of mesenchymal origin. Accordingly, panels of mesenchymal
      tumors have been interrogated for telomere maintenance mechanism, as well as
      characteristics such as tumor grade and patient survival. SUMMARY: These studies
      indicate a strong positive correlation between the activation of a telomere
      maintenance mechanism and tumor progression in sarcomas. In addition, the
      activation of either ALT or telomerase is correlated with poorer patient
      prognosis as compared with a lack of telomere maintenance. Ongoing studies aimed
      at elucidating the roles of ALT and telomerase in tumorigenesis should ultimately
      allow for the development of strategies to improve treatment of these
      malignancies.

PMID- 17545804
TI  - Don't believe ... check!!

PMID- 17545805
TI  - Neoadjuvant treatment in upper gastrointestinal adenocarcinomas: new paradigms
      from old concepts?
AB  - PURPOSE OF REVIEW: Despite a decline in the incidence of upper gastrointestinal
      adenocarcinomas in North America and western Europe during the past century,
      treatment remains a challenging problem for oncologists. The poor outcome
      associated with surgical resection with curative intent has generated intensive
      investigation of combined modality treatment approaches including systemic
      chemotherapy to prevent recurrences and improve overall mortality. This article
      reviews data on neoadjuvant and perioperative treatment modalities for upper
      gastrointestinal adenocarcinomas. RECENT FINDINGS: Postoperative chemoradiation
      is favored in the USA for good performance status patients with resected, high
      risk gastric or gastroesophageal junction carcinoma (more stage IA). More
      recently, the UK Medical Research Council Adjuvant Gastric Infusional
      Chemotherapy (MAGIC) and Federation Nationale des Centres de Lutte Contre le
      Cancer-Federation Francophone de Cancerologie Digestive trials results, showing
      survival benefit with perioperative chemotherapy in operable gastric and lower
      esophageal cancers, have had an impact on the treatment practice in Europe.
      SUMMARY: Novel strategies, involving induction with chemotherapy followed by
      preoperative chemoradiation, addition of targeted therapies to perioperative
      chemotherapy or use of new cytotoxic regimens are under evaluation to improve
      current standards and try to tailor therapeutic strategies.

PMID- 17545806
TI  - Targeted agents in the treatment of pancreatic cancer: history and lessons
      learned.
AB  - PURPOSE OF REVIEW: The treatment of pancreatic cancer is an ongoing challenge
      with minimal substantive improvement in patient outcomes despite many randomized
      phase III clinical trials evaluating multiple agents, both alone and in
      combination. Such disappointing outcomes clearly call for broadening the scope of
      pharmacologic approaches to managing this disease. With increasing insight into
      pathways within tumor cells that are related to tumor growth and spread, and
      development of 'targeted therapies' against these pathways, much attention has
      turned to the use of these agents, alone or coupled with chemotherapy, in the
      treatment of pancreatic cancer. RECENT FINDINGS: Several targeted agents have
      been studied in patients with pancreatic cancer. Of the agents studied, the only
      agent that has shown to provide a modest but significant benefit in survival for
      these patients is erlotinib, an epidermal growth factor receptor tyrosine kinase
      inhibitor. SUMMARY: From trials done to date, minimal benefit has been found with
      the addition of targeted agents in the treatment of pancreatic cancer. More
      potential pathways remain to be targeted, however, and there are a plethora of
      new agents to be tested. Due to the likelihood that different pathways drive the
      development and growth of different tumors of the same site of origin the
      inclusion of biomarker studies to correlate with treatment effect may be a
      necessary component of clinical trials to learn how to best tailor therapy to the
      patient.

PMID- 17545807
TI  - Current treatment for localized anal carcinoma.
AB  - PURPOSE OF REVIEW: Chemoradiation represents the standard of care for most
      patients with localized squamous cell carcinoma of the anal canal. This article
      reviews randomized trials and recent studies on chemoradiation for anal cancer.
      RECENT FINDINGS: A recent randomized trial showed that patients treated with
      induction 5-fluorouracil/cisplatin followed by concurrent 5
      fluorouracil/cisplatin and radiotherapy had a higher colostomy rate than patients
      treated with concurrent 5-fluorouracil/mitomycin C and radiotherapy. It remains
      unclear whether this difference in the rate of colostomy was due to the
      chemotherapy agents, the use of induction therapy in the 5-fluorouracil/cisplatin
      arm, or other factors. Recent studies have started to evaluate intensity
      modulated radiation therapy for anal cancer, in an effort to reduce acute and
      long-term toxicity from radiotherapy. SUMMARY: The role of cisplatin in anal
      cancer is not completely clear, although an ongoing randomized trial (Anal Cancer
      Trial II) may help clarify the role of cisplatin. Studies on tumor biology and
      patient genetics are warranted to identify patients that are most likely to
      benefit from newer locoregional and systemic therapies. Intensity modulated
      radiation therapy appears to be a promising approach for reducing treatment
      related toxicity in anal cancer patients. The Radiation Therapy Oncology Group
      (RTOG) is conducting a phase II trial evaluating the multi-institutional
      feasibility of intensity modulated radiation therapy for anal cancer.

PMID- 17545808
TI  - Health-related quality-of-life assessment in gastrointestinal cancer: are results
      relevant for clinical practice?
AB  - PURPOSE OF REVIEW: Health-related quality-of-life studies are now recognized as
      critical to understand the burden of disease and treatments on patients' well
      being. Significant advances have been recently achieved in gastrointestinal
      cancers, including the development and clinical use of new robust quality-of-life
      instruments. We review recent literature to evaluate whether quality-of-life
      assessment contributes to optimal patient information and helps treatment
      choices. RECENT FINDINGS: Treatments of gastrointestinal cancers have changed in
      the last few years with increasing use of multimodal therapies and advances in
      surgical techniques, especially for low-lying rectal cancers. Concurrent to the
      development of sphincter-saving procedures, however, the long-term consequences
      of a permanent stoma on quality of life have been debated. Results of new
      palliative treatments should also be considered looking at preservation or
      improvement of quality of life and not only prolongation of life. SUMMARY:
      Gastrointestinal malignancies impact strongly on patient quality of life due to
      the aggressiveness of the treatments. Short-term negative effects of surgery and
      specific deficits in survivors were recently described in gastrointestinal
      cancers. Baseline quality-of-life data predict length of survival in
      hepatocarcinoma and metastatic colorectal cancer. Generally, quality-of-life
      results help to fully inform the patients of the advantages or disadvantages of
      therapeutic options, including adjuvant and palliative treatments.

PMID- 17545809
TI  - Bibliography. Current world literature. Supportive care.

PMID- 17545812
TI  - When respecting patient autonomy may not be in the patient's best interest.

PMID- 17545814
TI  - Healthcare fraud: a primer for the nurse executive.
AB  - Healthcare fraud has become an issue about which all healthcare providers must be
      aware. Unfortunately, for most of us, the laws and the regulations developed to
      enforce the laws regarding fraud in healthcare are among the most confusing ever
      written. Healthcare fraud is an important area of risk for the nurse executive
      and an area about which all nurse executives need to be aware. Healthcare fraud
      primarily relates to improper billing of governmental healthcare programs. A
      basic understanding of these programs is therefore fundamental to understanding
      the problem of healthcare fraud and how to prevent it. This article will provide
      a basic overview of this subject for the nurse executive.

PMID- 17545816
TI  - The case for criminal background screening: informed licensure decision making.

PMID- 17545818
TI  - Preparing for the worst while hoping for the best: the relevance of hope in the
      heart failure illness trajectory.
AB  - BACKGROUND: Patients with heart failure have higher mortality rates than those
      with most malignant diseases. The heart failure illness trajectory is one of
      gradual decline characterized by unpredictable events such as acute
      decompensation of heart failure or a sudden cardiac death. Health professionals
      have an obligation to give patients and their families concise and honest
      information concerning their prognosis. The challenge exists to give what
      ostensibly may seem a bleak prognosis within a context of hope and optimism. AIM:
      To explore the role of hope in heart disease and the potential utility of this
      construct in the development of nursing interventions. METHODS: The electronic
      databases CINAHL, MEDLINE, EmBASE, and PSYCHlit were searched from 1982 to August
      2004 using the key words "hope," "hopelessness," "heart disease," and "heart
      failure." Articles were subsequently sorted to meet the inclusion criteria of (1)
      a philosophical discussion of the construct of hope and/or (2) investigation of
      hope in heart disease. RESULTS: This search retrieved 768 articles, and 24 met
      the inclusion criteria. Key findings from the review indicate that "hope" and
      "hopelessness" are underdeveloped, yet important constructs and conceptually
      linked with depression and spirituality. Intriguing findings from descriptive,
      observational studies have demonstrated the positive impact of expression of hope
      on cardiovascular outcomes. These findings need to be validated in randomized
      controlled trials. CONCLUSIONS: This critical literature review has determined
      that "hope" is strongly associated with the individual's future orientation.
      Increased understanding of this concept may assist in refining patient-focused
      interventions and developing therapeutic strategies to enhance hope.

PMID- 17545819
TI  - Improving outcomes for acute coronary syndrome patients in the hospital setting:
      successful implementation of the American Heart Association "Get With The
      Guidelines" program by Phase I cardiac rehabilitation nurses.
AB  - A treatment gap exists between published guidelines for secondary prevention of
      cardiovascular disease and application of these guidelines in clinical practice.
      The "Get With The Guidelines" program is a quality initiative developed by the
      American Heart Association to help acute care providers bridge this gap, thereby
      decreasing morbidity and mortality from cardiovascular disease. This article
      describes how cardiac rehabilitation nurses successfully implemented the program
      using a prospective case-management model in the acute care setting. An overview
      of the program including purpose, benefits, tools, and resources is provided
      along with start-up considerations, potential barriers, training needs, and keys
      to success.

PMID- 17545820
TI  - Sleep disturbances in people living with heart failure.
AB  - Approximately 10% to 70% of people living with chronic heart failure (HF)
      experience significant sleep disturbances, which have been shown to impair their
      health-related quality of life and overall functional performance. Research
      findings, however, report inconsistent conclusions about sleep disturbances and
      their adverse effects on HF. The purpose of this article is to review several
      research studies addressing sleep disturbances in patients with HF and to
      highlight contradictory and inconsistent findings. Further nursing research about
      the phenomena related to sleep disturbances in people with HF is warranted so
      that evidence-based assessments and interventions can be tested in the future.

PMID- 17545821
TI  - Interpreting 12-lead electrocardiograms for acute ST-elevation myocardial
      infarction: what nurses know.
AB  - In patients with acute myocardial infarction, early reperfusion and sustained
      patency of the culprit artery are important determinants of survival. The 12-lead
      electrocardiogram (ECG) is considered the noninvasive gold standard for
      identification of acute ST-elevation myocardial infarction. Nurses play a
      critical role in the process of obtaining, interpreting, and communicating ECG
      findings. This study evaluates nurses' ability to differentiate ischemic from
      nonischemic ECG patterns, to detect affected ECG leads and location of ischemia,
      and assesses skill level by hospital unit type. Seventy-five nurses were given a
      set of 6 patient scenarios, each with a corresponding 12-lead ECG, and asked to
      identify the presence or absence of ischemia. Fourteen (19%) of the 75 nurses
      correctly identified the presence or absence of ischemia in all 6 scenarios. Of
      the 3 ECGs with a myocardial infarction pattern, 59 (79%) of the nurses
      identified all 3 as ischemic; however, no one was able to determine the correct
      leads, location, or amplitude of ST-segment elevation. For the 3 nonischemic
      ECGs, 37 (49%) of the nurses identified a normal ECG as ischemic, 47 (63%)
      determined that an early repolarization pattern was ischemic, and 34 (45%)
      indicated that a left bundle branch block pattern was ischemic. These results not
      only identify educational opportunities but also provide important information
      for researchers implementing clinical trials evaluating the use of bedside ECG
      monitoring systems for detection of acute myocardial ischemia.

PMID- 17545823
TI  - Supraventricular dysrhythmias: nursing research to improve health outcomes.
AB  - Cardiovascular nursing practice includes accountability for the clinical and
      organizational processes to ensure positive outcomes for patients having cardiac
      dysrhythmias. For patients with supraventricular dysrhythmias, nurses have
      studied patient outcomes related to mortality, morbidity, quality of life,
      psychological and physical functioning, and symptoms. Nurses have also explored
      these same outcomes associated with the management of supraventricular
      dysrhythmias. In addition, nurses have contributed to understanding
      organizational outcomes such as healthcare utilization and costs associated with
      these patients. For patients with atrial fibrillation after cardiac surgery,
      nurses have studied patient and organizational outcomes related to mortality,
      morbidity, symptoms, psychological and physical functioning, and economic
      outcomes. This research has included numerous interdisciplinary studies, and most
      of it has been descriptive or observational in design. Areas for future nursing
      outcomes research, including more interventional studies, are discussed.

PMID- 17545824
TI  - Cardiovascular risk reduction in high-risk pediatric patients: a scientific
      statement from the American Heart Association Expert Panel on Population and
      Prevention Science; the Councils on Cardiovascular Disease in the Young,
      Epidemiology and Prevention, Nutrition, Physical Activity and Metabolism, High
      Blood Pressure Research, Cardiovascular Nursing, and the Kidney in Heart Disease;
      and the Interdisciplinary Working Group on Quality of Care and Outcomes Research.
AB  - Although for most children the process of atherosclerosis is subclinical,
      dramatically accelerated atherosclerosis occurs in some pediatric disease states,
      with clinical coronary events occurring in childhood and very early adult life.
      As with most scientific statements about children and the future risk for
      cardiovascular disease, there are no randomized trials documenting the effects of
      risk reduction on hard clinical outcomes. A growing body of literature, however,
      identifies the importance of premature cardiovascular disease in the course of
      certain pediatric diagnoses and addresses the response to risk factor reduction.
      For this scientific statement, a panel of experts reviewed what is known about
      very premature cardiovascular disease in 8 high-risk pediatric diagnoses and,
      from the science base, developed practical recommendations for management of
      cardiovascular risk.

PMID- 17545825
TI  - Concordance between routine interictal magnetoencephalography and simultaneous
      scalp electroencephalography in a sample of patients with epilepsy.
AB  - Both electroencephalography (EEG) and magnetoencephalography (MEG) localize
      epileptiform activity but may yield different results. This discordance may arise
      from different detection capabilities or from different data collection and
      interpretation techniques. Comparisons of MEG and EEG have focused on detection
      of individual spikes. However, side-by-side comparisons of results as used in the
      clinical setting is lacking. In this report, we present our empirical comparison.
      We reviewed 58 simultaneous MEG-EEG recordings (35 paired-sensors, 23 whole-head)
      from a diverse epilepsy population, comparing previous clinical MEG
      interpretations with new blinded EEG interpretations, noting lobar concordance of
      readers' judgments of regional abnormalities. A second-pass unblinded analysis,
      using all available clinical data, assessed the relative contribution and
      plausibility of the results of each technique. Concordance was high (85%)
      overall. Discordance was sometimes caused by constraints imposed by MEG dipole
      fitting techniques. Even when results of the techniques did not match, MEG often
      disambiguated the clinical scenario, especially when combined with imaging
      information. Thoughtful analysis of combined MEG-EEG datasets, beyond algorithm
      based interictal spike detection, can help guide clinical decision-making even
      when concordance between techniques is imperfect. In some cases, EEG and MEG are
      synergistic and provide complementary information.

PMID- 17545826
TI  - Removal of EEG noise and artifact using blind source separation.
AB  - A study was performed to investigate and compare the relative performance of
      blind signal separation (BSS) algorithms at separating common types of
      contamination from EEG. The study develops a novel framework for investigating
      and comparing the relative performance of BSS algorithms that incorporates a
      realistic EEG simulation with a known mixture of known signals and an objective
      performance metric. The key finding is that although BSS is an effective and
      powerful tool for separating and removing contamination from EEG, the quality of
      the separation is highly dependant on the type of contamination, the degree of
      contamination, and the choice of BSS algorithm. BSS appears to be most effective
      at separating muscle and blink contamination and less effective at saccadic and
      tracking contamination. For all types of contamination, principal components
      analysis is a strong performer when the contamination is greater in amplitude
      than the brain signal whereas other algorithms such as second-order blind
      inference and Infomax are generally better for specific types of contamination of
      lower amplitude.

PMID- 17545827
TI  - Clinical and electroencephalographic features of patients with polymicrogyria.
AB  - Polymicrogyria is a malformation of cortical organization. The aim of this
      historic cohort study was to describe clinical and EEG features of patients with
      polymicrogyria. Patients underwent clinical and neurologic examination and a
      prolonged routine EEG to allow recording during sleep. Neuroimaging data were
      classified as: perisylvian polymicrogyria (subdivided into holosylvian, posterior
      parietal, and generalized), hemispheric polymicrogyria, and frontal
      polymicrogyria. Forty patients were studied: 16 with holosylvian polymicrogyria,
      14 with posterior parietal polymicrogyria, 4 with generalized polymicrogyria, 3
      with hemispheric polymicrogyria, and 3 with frontal polymicrogyria. Patients with
      polymicrogyria usually did not have epilepsy and their EEGs were mostly normal
      (55%); the severity of the clinical and EEG features correlated with the extent
      of the cortical lesion. In perisylvian polymicrogyria, epileptiform abnormalities
      predominated in fronto-temporal regions. Dour patients had focal electrical
      status (FES) in awakeness and electrical status epilepticus of sleep (ESES);
      these four patients had right hemispheric polymicrogyria and asymmetric bilateral
      perisylvian polymicrogyria, mostly on the right hemisphere. The authors conclude
      that the EEG is usually normal in patients with polymicrogyria, despite it being
      associated with FES and ESES in certain patients.

PMID- 17545828
TI  - Rhythmic artifact of physiotherapy in intensive care unit EEG recordings.
AB  - Intensive care unit EEG recordings are often contaminated by artifacts that are
      unseen elsewhere and are usually not documented. One is the rhythmic artifact of
      physiotherapy (RAP), which can follow the frequency of chest percussion or
      vibration with either fundamental or harmonic sinusoidal wave forms, affecting
      single or multiple channels. The occipital electrodes are the most commonly
      affected, but others can be involved separately or in combination. RAP can easily
      be mistaken for cerebrally originating rhythms, including seizures. RAP is most
      easily detected by examining the ECG channel, which usually captures the
      artifact, but video EEG provides another means, at least for chest percussion.

PMID- 17545829
TI  - Comparative source localization of electrically and pressure-stimulated
      multichannel somatosensory evoked potentials.
AB  - The purpose of the study was to determine if there is a difference in the
      determination of the cortical hand area by dipole source estimation after
      artificial and natural stimuli. In principle, there are advantages of both
      methods: pressure stimulation is less invasive and compatible to fMRI, whereas
      electrical stimulation can be applied with higher stimulus rates and elicits
      sharper waveforms. Electrical and pressure stimulation was performed
      simultaneously on the thumb and fifth finger on eight healthy volunteers. The
      somatosensory evoked potentials after electrical stimulation showed sharper peaks
      and higher amplitudes than the pressure stimulated potentials. For the two
      stimulus qualities, cortical source positions of thumb and fifth finger separated
      significantly in the vertical z-axis. Both methods deliver reliable stimulation
      and therefore allow separate source localization of thumb and fifth finger. For
      cortical plasticity studies, peripheral somatosensory stimulation is of great
      importance. According to these findings, the choice of method, electrical or
      mechanical stimulation, may depend on practical criteria.

PMID- 17545830
TI  - Delayed N100m latency in focal epilepsy associated with spike dipoles at the
      primary auditory cortex.
AB  - Using magnetoencephalography (MEG), auditory evoked magnetic N100m were measured
      in patients with focal epilepsy and the influence of focal interictal epileptic
      spikes on primary auditory cortex (PAC) was evaluated. Spontaneous cerebral
      magnetic fields and auditory evoked magnetic fields were recorded in 40 epileptic
      patients and 9 healthy volunteers using MEG and latency of N100m in the bilateral
      hemisphere, and the distribution of epileptic spike dipoles were measured.
      Depending on the presence of structural lesions and the localization of spike
      dipoles, the patients were divided into groups as follows: group I, patients with
      structural lesions in PAC; group II, patients without structural lesions and with
      spike dipoles in PAC; and group III, patients with neither structural lesions nor
      spike dipoles in PAC. Nine healthy volunteers were recruited and evaluated as
      control group. Compared with group III and the control group, N100m latencies in
      groups I and II were significantly delayed. A delay in N100m latency was found
      not only among patients with structural lesions in PAC, but also among patients
      demonstrating cluster of epileptic spike dipoles in PAC. This finding indicates
      that the presence of epileptic spikes may influence the mechanism of processing
      auditory information in PAC.

PMID- 17545831
TI  - Antiepileptic drugs and the significance of event-related potentials.
AB  - The authors compared cognitive changes in epilepsy patients with or without
      antiepileptic drugs using event-related potential (ERP) N270 and P300. The
      patients were divided into three groups according to treatment type:
      carbamazepine, valproate acid (VPA), or no treatment. One control group composed
      of healthy subjects was included. The Mini-Mental State Examination detected no
      clinical dementia in all subjects. A modified Sternberg paradigm was used as a
      task when an ERP was recorded. When a stimulus was different from the memorized
      item (conflict condition), N270 was elicited in both controls and patients. All
      the three patient groups showed a delayed and smaller N270 than the control
      group. P300 was elicited when a stimulus was the same one as the memorized item
      (match condition), and its amplitude decreased in the VPA group. P300 latency did
      not differ among the four groups. ERP (N270 and P300) was abnormal in patients
      with epilepsy. These results indicate that antiepileptic drugs, especially VPA,
      might enhance the impairment of cognitive processing. N270 is more sensitive than
      P300 in the early detection of minor cognitive impairment in epileptics.

PMID- 17545832
TI  - Pattern-induced negative occipital potentials (PINOP).
AB  - SUMMARY: : We describe 24 subjects (16 female, 8 male; age range, 3 to 36 years
      [mean, 15.7]) who exhibited a hitherto inadequately described EEG response to
      visual scanning of geometric patterns. Like lambda waves (the normal physiologic
      response to visual scanning of pictures), the responses to pattern scanning were
      occipitally distributed and disappeared on eye closure. In contrast to lambda
      waves, they were surface negative, briefer in duration, and sharper in contour.
      To designate them, we have coined the term pattern-induced negative occipital
      potentials (PINOP). The prevalence of epilepsy was not significantly different
      among subjects with PINOP than among age- and sex-matched control subjects who
      did not have PINOP. None of the patients with PINOP exhibited paroxysmal
      epileptiform responses to intermittent photic stimulation or pattern activation.
      We conclude that PINOP represent an unusual benign physiologic phenomenon. The
      restricted distribution over the posterior head region and absence of associated,
      more widely distributed epileptiform responses during photic stimulation and
      pattern testing are clues to the diagnosis. We hypothesize that a differential
      area of activation in the occipital lobe during pattern viewing versus picture
      viewing and orientation of the activated areas to the scalp electrodes may
      account for the differences in the morphology of the wave forms observed during
      conventional EEG recording.

PMID- 17545833
TI  - Success rate of motor evoked potentials for intraoperative neurophysiologic
      monitoring: effects of age, lesion location, and preoperative neurologic
      deficits.
AB  - Transcranial electrical stimulation with myogenic motor evoked potential (MEP)
      recording was used for intraoperative neurophysiologic monitoring in 341
      consecutive "high-risk" neurosurgical or orthopedic procedures. Overall, the
      success rate for establishing reliable MEP response was 94.8% for upper
      extremities and 66.6% for lower extremities. The rate was only 39.1% for lower
      extremities in patients with preoperative motor deficit and up to 81% in
      neurologically intact adults. Further analysis demonstrated that extremes of age
      or the presence of a lesion in the spinal cord and motor deficit contributed to
      failure in obtaining reliable MEPs.

PMID- 17545834
TI  - Individual variation in human motor-sensory (rolandic) cortex.
AB  - Eloquent cortex is generally identified using a variety of techniques including
      direct electrical stimulation to identify motor-sensory, language, and memory
      cortex and somatosensory evoked potentials to identify motor-sensory cortex. It
      is important that these areas of cortex be identified so as to prevent damage
      during the course of neurosurgical procedures. Seventy epilepsy patients
      undergoing evaluation for epilepsy surgery with chronically implanted subdural
      grids were retrospectively studied using both somatosensory evoked potentials and
      direct electrical stimulation. Direct electrical stimulation of motor-sensory
      cortex elicited responses over a larger area than did somatosensory evoked
      potentials. A great deal of individual variation was identified using both
      techniques. The results presented here support previous conclusions that the
      concept of homunculus somatotopy (point to point representation) of the motor
      sensory cortex be abandoned and that of functional mosaicism of the motor-sensory
      cortex replace the earlier model. The individual variation found in the human
      motor-sensory cortex will require a continuation of "brain mapping" to identify
      eloquent cortex so that these vital areas will be spared during neocortical
      neurosurgical procedures.

PMID- 17545835
TI  - Conduction velocities of Adelta-fibers and C-fibers in human peripheral nerves
      and spinal cord after CO2 laser stimulation.
AB  - Conduction velocities (CVs) in two nociceptive afferents were estimated to
      clarify the mechanism of pain transmission. Late and ultra-late laser evoked
      potentials (LEPs) were recorded by stimulating Adelta- and C-nociceptive nerve
      endings at different skin sites (the hand, foot, and skin overlying the 7th
      cervical and 12th thoracic vertebrae), by which data CVs of the arm (CVA), leg
      (CVL), and spinothalamic tract (CVSTT) were estimated. In late LEPs, Adelta-CVA
      and Adelta-CVL respectively were between 6.7 and 23.7 (mean +/- SD, 12.8 +/- 5.2)
      m/s, and 9.0 and 26.7 (17.2 +/- 5.6) m/s. Adelta-CVSTT was between 4.1 and 22.1
      m/s (10.6 +/- 5.8). In ultra-late LEPs, C-CVA and C-CVL respectively varied
      between 1.0 and 2.1 (mean +/- SD, 1.5 +/- 0.3) m/s, and 1.0 and 1.9 (1.4 +/- 0.2)
      m/s. C-CVSTT was between 1.0 and 3.9 (1.8 +/- 0.8) m/s. No significant difference
      was found among CVA, CVL, and CVSTT values calculated from late or ultra-late LEP
      latencies. Nociceptive signals of the primary Adelta- and C-afferents therefore
      may be conveyed separately by myelinated (Adelta-) and unmyelinated (C) axons
      through peripheral nerves and spinal cord.

PMID- 17545836
TI  - Diagnostic accuracy of thoracic paraspinal electromyography in amyotrophic
      lateral sclerosis.
AB  - The goal of this study was to estimate the accuracy of thoracic paraspinal (T
      PSP) electromyography (EMG), performed at the time of initial evaluation, for the
      subsequent clinical diagnosis of amyotrophic lateral sclerosis (ALS). Medical
      records from a consecutive series of patients referred for suspected ALS were
      abstracted. Those in whom T-PSP EMG was not performed or for whom follow-up was
      not available were excluded. The study population included 64 patients. T-PSP EMG
      was abnormal in 28 (44%) study patients, 26 (93%) of whom were subsequently
      diagnosed with ALS. T-PSP EMG showed neither fibrillation potentials nor positive
      sharp waves in 36 (56%) patients, 9 (25%) of whom later developed ALS. The
      sensitivity of T-PSP for the diagnosis of ALS was 0.74 and the specificity was
      0.93. The likelihood ratio positive was 10.5 and the likelihood ratio negative
      was 0.28. These results suggest that T-PSP EMG is very useful for "ruling in" the
      diagnosis of ALS, but less useful as a screening test for "ruling out" the
      diagnosis. Because T-PSP EMG is used clinically in an effort to confirm the
      diagnosis (and not as a screening test), these results suggest that T-PSP EMG is
      an extremely useful adjunct for the diagnosis of ALS.

PMID- 17545837
TI  - Fasciculation potentials in high-density surface EMG.
AB  - Fasciculation potentials (FPs) are observed in healthy individuals, but also in
      patients with neurogenic disorders. The exact site of origin and the clinical
      relevance in distinguishing, for example, amyotrophic lateral sclerosis (ALS)
      from other neurogenic diseases based on specific characteristics of the FPs is
      still a matter of debate and needs further exploration. This report describes the
      use of high-density surface EMG (HD-sEMG), with multiple electrodes in a compact
      grid to noninvasively record FPs. The technique provides both temporal and
      spatial information of fasciculations. Examples of the FPs of a patient diagnosed
      with definite ALS are presented. FPs are shown in different electrode montages
      and the unique spatial characteristics of different FPs are presented. During 30
      second recordings, 137 FPs were detected that via a decomposition algorithm could
      be assigned to 11 different underlying sources. It is concluded that HD-sEMG,
      both because of its noninvasive character and the unique spatiotemporal
      information, is very suitable to examine fasciculations. It allows long stable
      recording times and provides quantitative information. This electrophysiologic
      tool is expected to expand the existing knowledge of FP properties.

PMID- 17545838
TI  - Alpha coma and locked-in syndrome.

PMID- 17545839
TI  - Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) pathway
      signaling.
AB  - Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)/Apo1L is a death
      ligand, a cytokine that activates apoptosis through cell surface death receptors.
      TRAIL is thought to be important in host tumor surveillance and metastasis
      suppression, and various therapeutic agonists that activate TRAIL receptors to
      induce tumor cell apoptosis are in clinical development. This review discusses
      recent findings about TRAIL pathway signaling and relates the signaling
      mechanisms to issues that need to be considered as we try to manipulate TRAIL
      signaling to treat cancer.

PMID- 17545840
TI  - Specific features of non-small cell lung cancer in women: a retrospective study
      of 1738 cases diagnosed in Bas-Rhin between 1982 and 1997.
AB  - INTRODUCTION: The literature suggests that lung cancer may represent a different
      disease in women compared with men and that gender specificities have been
      reported mostly in clinical trials patients. METHODS: We conducted a
      retrospective, population-based study of a sample of 1738 patients diagnosed with
      a non-small cell lung cancer (NSCLC) in the department of Bas-Rhin (northeastern
      France) between 1982 and 1997. Our study aimed to describe symptoms at
      presentation, stage, histological distribution, treatment modalities, and
      survival, according to sex. RESULTS: Tobacco exposure differed significantly
      according to sex: 28.9% of women were nonsmokers versus 1.4% of the men. More
      NSCLC were metastatic at diagnosis in women than in men (41.1% versus 29.9%).
      Adenocarcinoma predominated in women (54.4%), whereas squamous cell carcinoma
      predominated in men (65.9%). Invasive procedures, such as transthoracic needle
      biopsy, contributed more frequently to histological diagnosis in women. Men and
      women underwent the same procedures for disease staging, excepted for the
      abdominal computed tomography scan, which was performed more frequently in women.
      Treatment also differed: in resectable disease, fewer pneumonectomies were
      performed in women; in locally advanced disease, the mean doses of thoracic
      irradiation were significantly lower in women (48.0 grays versus 55.5 grays); in
      metastatic-stage disease, fewer women received platin-based chemotherapy, but
      this difference was not significant. Sex was not a significant prognostic factor
      in our study, contrary to most North American studies, where women seem to have
      had better survival rates. CONCLUSIONS: This study emphasizes gender differences
      in smoking exposure, presentation (stage, histological subtype), and diagnostic
      and therapeutic management of NSCLC.

PMID- 17545841
TI  - Informal caregiving burden in advanced non-small cell lung cancer: the HABIT
      study.
AB  - INTRODUCTION: This study's aim was to assess economic data regarding the home
      assistance burden for advanced non-small cell lung cancer (NSCLC) patients in
      Italy. PATIENTS AND METHODS: One hundred four NSCLC patients in second-line
      chemotherapy (2LC) or in supportive therapy (ST) were enrolled in 18 Italian
      oncology departments and were observed for 3 months. The main caregiver's
      workload was assessed monthly by a task scale; other caregivers' activities were
      also registered. Eastern Cooperative Oncology Group performance status was
      assessed by physicians, and patients completed the Lung Cancer Symptoms (LCS)
      subscale. Formal caregiving time was valued according to market prices; informal
      caregiving hours were valued using the wage rate for an equivalent service.
      Covariance analysis was performed to check for influential factors in assistance
      costs. RESULTS: The mean age of the total sample was 65.5 years, and prevalence
      of males was over 80%. In over 70% of cases, the principal caregiver was
      patient's spouse, living with the patient and not working. Principal caregiver
      support was the main cost item: 2.368 euros in 2LC and 2.805 euros in ST,
      representing 74% of total trimonthly assistance costs. Regression analysis showed
      a positive correlation between the severity of symptoms and the costs of
      assistance. The caregiving burden was higher in patients with bone and/or
      cerebral metastases; other metastasis sites seemed to have no impact on
      assistance costs. CONCLUSION: Considering quality of life as the ultimate health
      outcome, clinicians are challenged to contribute to a research and policy agenda
      that holds burden of care in due consideration.

PMID- 17545842
TI  - Lung cancer in New Zealand: patterns of secondary care and implications for
      survival.
AB  - INTRODUCTION: The survival of patients with lung cancer in New Zealand is poor
      compared with Australia and the United States. To determine whether these poorer
      outcomes were related to secondary care management or to other factors, we
      documented stage of disease, comorbidities, and initial secondary care management
      for patients diagnosed with lung cancer in 2004, in Auckland and Northland (New
      Zealand). These data were compared with international data. METHODS: Cases were
      identified from regional databases and the New Zealand Cancer Registry. Patient,
      tumor, and management details were collected from clinical records. RESULTS: Five
      hundred sixty-five eligible cases were identified: 55% were male, the median age
      was 69 years, 9% were never-smokers, 81% had documented comorbidity, and 32%
      belonged to the most deprived socioeconomic quintile. Histopathology was non
      small cell lung cancer (NSCLC) in 70%, small-cell lung cancer (SCLC) in 13%, 2%
      other types, and 15% clinicoradiological diagnoses. At presentation, 70% of NSCLC
      cases had locally advanced/metastatic disease, and 65% of SCLC cases had
      extensive disease. Overall, 70% of cases were referred to an anticancer service,
      and 50% received initial anticancer treatment. Potentially curative treatment was
      received by 20% of cases: 56% stage I/II, 10% stage III NSCLC, and 58% limited
      stage SCLC. CONCLUSIONS: This cohort was characterized by high comorbidity and
      advanced disease. Although similar to the United Kingdom, initial treatment rates
      were low in comparison with Australia and the United States, despite similar
      stage distributions. Overall, 50% of patients, including 30% with early-stage
      disease, did not receive initial anticancer treatment. Low anticancer treatment
      rates may contribute to poorer survival outcomes in New Zealand.

PMID- 17545843
TI  - Chemotherapy in patients > or = 80 with advanced non-small cell lung cancer:
      combined results from SWOG 0027 and LUN 6.
AB  - INTRODUCTION: We report outcomes for the combined cohort of patients ages 80 or
      older from two chemotherapy trials in advanced non-small cell lung cancer (NSCLC)
      conducted by the Southwest Oncology Group (S0027) and an investigator-initiated
      trial (LUN 6). METHODS: Patients with chemotherapy-naive, stage IIIB/IV NSCLC,
      ages 70 years or older with a performance status (PS) of 0 or 1, or patients of
      any age with PS 2, were eligible. Treatment in the S0027 study was 25 mg/m2 of
      vinorelbine on days 1 and 8, every 21 days for three cycles, and then 35 mg/m2 of
      docetaxel on days 1, 8, and 15, every 28 days for three cycles. Treatment in the
      LUN 6 study was 30 mg/m2 of docetaxel on days 1, 8, and 15, every 28 days, or 75
      mg/m2 every 21 days. Of the 228 patients treated, 49 (21.5%; 26 in LUN 6 and 23
      in S0027) were ages 80 years or older. Analysis of outcome was conducted in the
      80-and-older group and was compared with the under-80 cohort from S0027. RESULTS:
      Among patients with measurable disease, disease-control rates (partial response +
      stable disease) were 54% (n = 48) and 46% (n = 89) in the 80-and-older and under
      80 groups, respectively. Median survival was 7 and 11 months in PS 0/1 patients
      in the 80-and-older and under-80 groups, respectively. Median survival was 4 and
      5 months in PS 2 patients in the 80-and-older and under-80 groups, respectively.
      Treatment was well tolerated. Five treatment-related deaths were noted: two (4%)
      and three (3.4%) in the 80-or-younger and the under-80 groups, respectively.
      CONCLUSIONS: These chemotherapy regimens were associated with an encouraging
      disease-control rate (54%) in patients 80 years or older with advanced NSCLC,
      with good tolerance. Selected octogenarians with advanced NSCLC may benefit from
      single-agent chemotherapy.

PMID- 17545844
TI  - Clinical stage I non-small cell lung cancer including FDG-PET Imaging: sites and
      time to recurrence.
AB  - INTRODUCTION: Positron emission tomography (PET) has improved the accuracy of
      staging non-small cell lung cancer (NSCLC), although some early-stage patients
      will still relapse. The purpose of this study was to determine the sites and time
      to recurrence in patients with clinical stage I NSCLC whose initial staging
      evaluation included conventional imaging and fluorodeoxyglucose-PET. METHODS:
      This study was approved by our institutional review board and complies with the
      Health Insurance Portability and Accountability Act. We retrospectively searched
      our PET database and identified 231 patients (125 women, 106 men; ages 36-93
      years) with primary NSCLC and clinical stage I disease. The sites and time to
      recurrence were recorded. The average follow-up time was 33 months. RESULTS: Of
      the 231 patients with clinical stage I tumors, 196 patients (85%) had
      pathological stage I disease. Two patients developed a second primary lung
      cancer, and 40 patients (20%) developed local or distant recurrence. Ninety-three
      percent of all patients remained disease free at 1 year, and 27% (11/40) of those
      who recur do so in the first year. The most common site of first recurrence was
      the thorax, followed by the brain, bone, and adrenal glands. CONCLUSIONS: Twenty
      percent of stage I NSCLC patients staged with conventional imaging and PET will
      develop recurrent NSCLC. The sites of recurrence with the addition of PET are
      similar to those reported with staging by conventional imaging alone. Additional
      studies are needed to determine the optimal time for follow-up imaging if
      intervention for recurrent disease is shown to improve survival.

PMID- 17545845
TI  - Tolerability of accelerated chest irradiation and impact on survival of
      prophylactic cranial irradiation in patients with limited-stage small cell lung
      cancer: review of a single institution's experience.
AB  - INTRODUCTION: Evidence that has been published in the last decade indicates that
      in patients with limited-stage small-cell lung cancer (SCLC), hyperfractionated
      accelerated thoracic radiotherapy (RT) given twice daily and prophylactic cranial
      irradiation (PCI) have each separately improved survival. Concerns about the
      toxicities associated with these treatments and uncertainty about their impact on
      survival outside the trial setting may have restricted the extent to which they
      have been incorporated into standard treatment protocols. We have reviewed the
      experience at Peter MacCallum Cancer Centre to determine the tolerability of
      these treatments in routine practice and to determine their effects on survival.
      METHODS: A retrospective review of patients with limited-stage SCLC receiving a
      radical course of thoracic RT between June 1998 and May 2002, including either
      conventional fractionation at 50 Gy for 5 weeks, or hyperfractionated accelerated
      RT at 45 Gy for 3 weeks. Patients achieving a complete response were offered PCI
      at 36 Gy in 18 fractions. The main outcomes recorded were RT toxicity (graded
      using CTCAE v. 3.0 and RTOG/EORTC late scoring criteria), response, relapse-free
      survival, and overall survival. RESULTS: Ninety patients were identified as
      having undergone radical-intent thoracic RT, with a median potential follow-up of
      4.2 years. Fifty-seven patients (63%) were treated with hyperfractionated
      accelerated RT, and 33 (37%) were treated with conventional fractionation. Forty
      six patients (51%) received PCI. Patients receiving hyperfractionated accelerated
      RT compared with conventional fractionation had higher rates of grade 3 and 4
      esophagitis (14% versus 6%; p = 0.312), a higher rate of treatment interruptions
      (12% versus 3%; p = 0.250), and a higher hospital admission rate (39% versus 15%;
      p = 0.031). The majority of patients were able to complete the planned treatment,
      and there were no treatment-related deaths. Median survival for all patients from
      commencement of RT was 14.2 months (95% confidence interval [CI]: 11.9-18.1
      months), and survival at 2 years was 24.8% (95% CI: 16.9-35.0%). On multifactor
      analysis, the only factor associated with longer survival was PCI (hazard ratio =
      0.40; p < 0.001). CONCLUSIONS: Hyperfractionated accelerated RT was more toxic
      than conventional fractionation, but it was possible to deliver treatment as
      planned in the majority of patients. PCI was associated with improved survival.
      Both treatments can be incorporated into routine practice.

PMID- 17545846
TI  - The difficulties of a randomized study in superior vena caval obstruction.
AB  - INTRODUCTION: Superior vena caval obstruction (SVCO) is a not uncommon
      complication of malignant disease. Treatment may consist of radiation (RT) to the
      mediastinum, systemic therapy for chemosensitive tumors, and supportive measures
      such as oxygen and steroids. Advances in interventional radiology have allowed
      the introduction of expandable stents into the superior vena cava (SVC), with the
      theoretical advantage of providing symptom relief within hours, rather than the
      days and weeks over which RT exerts its effect. Although small case series have
      supported the use of stents in SVCO, there are no randomized data. METHODS: We
      set up a randomized study at Princess Margaret Hospital, Toronto. Patients were
      randomized to receive palliative RT to the mediastinum or immediate stenting of
      the SVC and then mediastinal RT within a week. The aim of the study was to
      compare symptom response between the two treatment arms. A second study, a
      prospective longitudinal study, was also set up to obtain information on symptom
      response and outcome regardless of the treatment given. RESULTS: In a 12-month
      period, we were unable to accrue any patients in the randomized study; of the 19
      patients approached, 13 have agreed to participate in the longitudinal study.
      CONCLUSIONS: In this report, we present the problems that we have encountered
      with these studies.

PMID- 17545847
TI  - A phase II trial of carboplatin/vinorelbine with pegfilgrastim support for the
      treatment of patients with advanced non-small cell lung cancer.
AB  - INTRODUCTION: The impact of chemotherapy dose delivery has not been well studied
      in patients with non-small cell lung cancer (NSCLC). Overlapping hematologic
      toxicities commonly limit planned dose intensity of combination chemotherapy
      regimens. A phase II study investigating carboplatin and vinorelbine, supported
      by pegfilgrastim, in the treatment of patients with advanced NSCLC was performed.
      METHODS: Chemotherapy-naive patients with locally advanced or metastatic NSCLC
      were treated with carboplatin area under the curve (AUC) 6 mg/ml per minute
      intravenously on day 1 and vinorelbine 30 mg/m2 intravenously on days 1 and 8
      every 3 weeks for four planned cycles. Pegfilgrastim was administered on day 9 of
      each cycle as a 6-mg subcutaneous injection. The primary endpoint was incidence
      of cycle 1 febrile neutropenia. Secondary endpoints included incidence of grade
      3/4 hematologic and nonhematologic toxicities, delivered dose intensity, and
      overall survival. RESULTS: Thirty patients (21 men, 9 women) with a median age of
      61 years (range, 43-79) were enrolled. Of 120 planned patient cycles, 101 (84%)
      were completed. There was one episode of cycle 1 febrile neutropenia. Overall
      response rate was 27%. Median dose delivered for vinorelbine was 17.2 mg/m2 per
      week, representing a delivered dose intensity of 86%. Median survival was 9.4
      months (95% confidence interval: 6.1-18.0) with a 3-year survival rate of 20%.
      CONCLUSIONS: This regimen of carboplatin and vinorelbine with pegfilgrastim
      support was associated with a low rate of febrile neutropenia and good
      maintenance of planned dose intensity. Although response and survival are similar
      to other chemotherapy regimens in advanced NSCLC, studies optimizing chemotherapy
      delivery in this setting may help inform treatment approaches in patients with
      earlier stage disease.

PMID- 17545848
TI  - Gemcitabine and irinotecan for patients with untreated extensive stage small cell
      lung cancer: SWOG 0119.
AB  - INTRODUCTION: To evaluate the activity of a nonplatinum-, nonetoposide-containing
      regimen for patients with extensive stage small cell lung cancer. METHODS:
      Patients with untreated extensive stage small cell lung cancer were treated with
      gemcitabine 1000 mg/m2 and irinotecan 100 mg/m2 on days 1 and 8 of a 21-day cycle
      for a maximum of six cycles. Patients with brain metastases were eligible if
      asymptomatic or controlled after radiation. RESULTS: Eighty-four eligible
      patients with untreated extensive stage small cell lung cancer with adequate
      organ function and a performance status of 0-2 were accrued. The median age was
      64 years (range, 42-85) and 45 (54%) were women. Six cycles were completed by 28
      (33%) patients. Some degree of diarrhea occurred in 57% (grade 3/4, 18%). Other
      grade 3/4 toxicities were neutropenia (26%), anemia (10%), thrombocytopenia (8%),
      febrile neutropenia (5%), fatigue (11%), nausea (10%), and vomiting (8%). The
      response rate was 32% (95% confidence interval: 22%-43%) among the 81 patients
      with measurable disease. The median survival was 8.5 months (95% confidence
      interval: 7.0-9.8) with 1- and 2-year survival rates of 26% and 7%, respectively.
      Salvage therapy data were captured by prospective collection, and only 50% of
      patients were treated secondarily. CONCLUSION: The overall response rate with the
      combination of gemcitabine and irinotecan was disappointing, and the median
      survival rate was lower than expected. Further development of this combination in
      small cell lung cancer is not recommended.

PMID- 17545849
TI  - Patterns of radiotherapy re-treatment in patients with lung cancer: a
      retrospective, longitudinal study.
AB  - INTRODUCTION: The optimal initial radiotherapy utilization rate for lung cancer
      is estimated to be 76% of all new cases. The actual re-treatment rate has not
      been defined. Re-treatment information can aid clinical decision making and
      resource planning. The aim of this study was to examine the indications for re
      treatment in a population cohort and report the proportion of patients who
      receive more than one radiotherapy treatment for lung cancer throughout their
      lifetime. METHODS: A retrospective longitudinal analysis of a cohort of patients
      with lung cancer treated with radiotherapy in the South Western Sydney Area
      Health Services (SWSAHS) in 1993 and 1996 was performed. The indication for and
      timing of all episodes of radiotherapy were recorded and analyzed using SPSS Data
      3.5 software (SPSS, Inc., Chicago, IL). RESULTS: Of the 527 patients diagnosed
      with lung cancer in the study period, 279(53%) were treated at least once with
      radiotherapy. Initial radiotherapy was palliative for 79%, definitive for 14%,
      and adjuvant for 7%. The most common sites of initial radiotherapy were chest
      (79%), bone (10%), and brain (9%). Of the 279 patients, 73 (27%) received
      treatment with a second course of radiotherapy, 19 (7%) had a third radiotherapy
      episode, and 6 (2%) had a fourth. One patient had five radiotherapy episodes.
      Overall, there were 328 radiotherapy courses delivered to the 279 patients.
      DISCUSSION: The re-treatment rate for our cohort was 27%, exceeding other
      estimations of re-treatment. Common sites re-treated were chest and bone. Re
      treatment was 17% of the initial linear accelerator treatment delivery work load
      for lung cancer.

PMID- 17545850
TI  - Independent review of interstitial lung disease associated with death in TRIBUTE
      (paclitaxel and carboplatin with or without concurrent erlotinib) in advanced non
      small cell lung cancer.
AB  - INTRODUCTION: A rare but serious complication of epidermal growth factor receptor
      (EGFR) tyrosine kinase inhibitor (TKI) therapy is a lung injury syndrome commonly
      referred to as a drug-induced interstitial lung disease (ILD). It has a typical
      clinical presentation of rapidly progressive acute or subacute dyspnea and a
      histopathology of diffuse alveolar damage (DAD). The incidence, severity, and
      risk factors for EGFR TKI-induced ILD remain poorly understood. Whether
      concurrent chemotherapy increases its risk is also unclear. The primary focus of
      this blinded review was to determine the incidence of ILD leading to death in
      1059 TRIBUTE patients randomized to chemotherapy plus erlotinib or placebo.
      METHODS: All fatal serious adverse events (SAEs) were reviewed by an independent
      three-person panel composed of a medical oncologist, radiologist, and
      pulmonologist not associated with the study and without knowledge of treatment
      assignment. Fatal respiratory SAEs were identified and assigned to one of four
      potential attributions: progressive cancer, concurrent illness, drug-induced ILD,
      or other toxicities not related to ILD. Each panel member first made an
      independent assignation; then each case was discussed jointly. If needed,
      consensus was reached by vote. RESULTS: Fatal SAEs were reported in 80 of 1059
      patients (7.6%): 53 of 526 patients on erlotinib (10.1%) and 27 of 533 on placebo
      (5.1%) (p < 0.05). Consensus assignation for 41 fatal respiratory SAEs was as
      follows: cancer, 18 (44%); concurrent illness, 15 (37%); other toxicities not
      related to ILD, five (12%); ILD, three (7%). All three ILD cases occurred in the
      erlotinib arm (3/526; 0.6%). The one biopsy-confirmed case of ILD revealed
      bronchiolitis obliterans organizing pneumonia, a histopathologic finding that has
      not previously been reported. All three cases of fatal ILD had a typical clinical
      presentation of acute or subacute onset of dyspnea with rapid progression to
      respiratory failure. CONCLUSIONS: This independent blinded analysis of the
      TRIBUTE study identified fatal ILD in 0.6% of cases treated with the combination
      of erlotinib plus chemotherapy, possibly higher than previous reports of EGFR
      TKIs alone in the non-Japanese population. Fatal ILD alone does not fully account
      for the imbalance in fatal SAEs observed in TRIBUTE. EGFR TKI-induced fatal ILD
      typically presents with acute or subacute dyspnea with rapid progression and a
      typical histopathology of diffuse alveolar damage both consistent with the acute
      respiratory distress syndrome, but can also be associated with a histopathology
      of bronchiolitis obliterans organizing pneumonia. Further studies designed to
      better understand the underlying pathophysiology and risk factors for ILD are
      needed.

PMID- 17545851
TI  - Spontaneous mediastinal hematoma presenting as a mass.
AB  - A 59-year-old man had undergone hemodialysis for 16 years because of chronic
      renal failure. The patient had taken an aspirin therapy (100 mg per day) for 4
      years because of his history of brain infarction. He had a 3-week history of
      increasing back pain. A chest computed tomographic scan demonstrated a mass in
      the upper mediastinum. The mass was located among the superior vena cava,
      trachea, and ascending aorta. Two weeks later, magnetic resonance imaging
      revealed that the mass had become slightly smaller. The patient's symptom also
      disappeared gradually. Follow-up imaging showed that the mass had resolved
      completely. The clinical and imaging findings corresponded with a case of
      spontaneous mediastinal hematoma presenting as a mass.

PMID- 17545852
TI  - Controversy about small peripheral lung adenocarcinomas: how should we manage
      them?
AB  - In recent years, the clinical use of high-resolution computed tomography has
      greatly advanced the diagnosis of small lesions of the peripheral lung. Such
      small lesions are often associated with ground-glass opacity in computed
      tomography findings. The noninvasive bronchioloalveolar carcinoma component with
      a replacement growth pattern of alveolar lining cells manifests as ground-glass
      opacity. Bronchioloalveolar carcinoma is classified as a subset of lung
      adenocarcinoma, but has a distinct clinical presentation, tumor biology, and
      favorable prognosis. Most small peripheral lung lesions including
      bronchioloalveolar carcinoma putatively originate from the peripheral airway
      epithelium, in which the epidermal growth factor receptor gene is frequently
      mutated. As with other subsets of non-small cell lung cancer, surgical resection
      is a potentially curative treatment. For the ground-glass opacity type of tiny
      lesions, particularly those less than 1 cm in their greatest dimension, the
      question has been raised whether lobectomy is really needed. Although several
      authors in Japan suggest the suitability of limited resection including
      segmentectomy and wedge resection without any nodal dissections for these small
      lung adenocarcinomas, this procedure should be validated in future clinical
      trials.

PMID- 17545853
TI  - Radiochemotherapy of esophageal cancer.
AB  - Cancer of the esophagus continues to be a threat to public health. The common
      practice is esophagectomy for surgically resectable tumors and radiochemotherapy
      for locally advanced, unresectable tumors. However, local regional tumor control
      and overall survival of esophageal cancer patients after the standard therapies
      remain poor, approximately 30% of patients treated with surgery only will develop
      local recurrence, and 50% to 60% patients treated with radiochemotherapy only
      fail local regionally due to persistent disease or local recurrence.
      Esophagectomy after radiochemotherapy or preoperative radiochemotherapy has
      increased the complete surgical resection rate and local regional control without
      a significant survival benefit. Induction chemotherapy followed by preoperative
      radiochemotherapy has produced encouraging results. In addition to patient-,
      tumor-, and treatment-related factors, involvement of celiac axis nodes, number
      of positive lymph nodes after preoperative radiochemotherapy, incomplete
      pathologic response, high metabolic activity on positron emission tomography scan
      after radiochemotherapy, and incomplete surgical resection are factors associated
      with a poor outcome. Radiochemotherapy followed by surgery is associated with
      significant adverse effects, including treatment-related pneumonitis,
      postoperative pulmonary complications, esophagitis and pericarditis. The
      incidence and severity of the adverse effects are associated with chemotherapy
      and radiotherapy dosimetric factors. Innovative treatment strategies including
      physically and biologically molecular targeted therapy is needed to improve the
      treatment outcome of patients with esophageal cancer.

PMID- 17545854
TI  - Hibernoma: 18F FDG PET/CT imaging.
AB  - The patient was a 40-year-old woman who was diagnosed with a malignant melanoma
      of the left posterior thigh. Follow-up positron emission tomography
      (PET)/computed tomography (CT) examination revealed an intensely FDG-avid lesion
      that predominantly contained fat in the right postero-lateral chest wall
      involving the latissimus dorsi. Ultrasound-guided fine needle aspirate and core
      biopsy confirmed the diagnosis of hibernoma rather than melanoma metastasis.

PMID- 17545855
TI  - Perforated viscus in a patient with non-small cell lung cancer receiving
      bevacizumab.
AB  - Bowel metastasis and perforation in patients with non-small cell lung cancer is
      rare. Bevacizumab has emerged as a new therapy in the treatment of metastatic non
      small cell lung cancer. Bowel perforation associated with its use has been
      described in colon and ovarian cancers. The exact mechanism by which perforation
      occurs is under debate, and many theories exist. In this report, we present the
      first known case of visceral perforation in a patient with metastatic non-small
      cell lung cancer after treatment with bevacizumab.

PMID- 17545856
TI  - Lung cancer management in the Asia-Pacific region: what's the difference compared
      with the United States and Europe? Results of the Second Asia Pacific Lung Cancer
      Conference.

PMID- 17545857
TI  - Chemotherapy and surgery in stage IIIa non-small cell lung cancer.

PMID- 17545858
TI  - Multidisciplinary management of lung cancer.

PMID- 17545861
TI  - Long-term efficacy of sublingual immunotherapy in patients with perennial
      rhinitis.
AB  - BACKGROUND: Sublingual immunotherapy has a documented clinical efficacy, but only
      a few long-term studies have been performed in people with perennial rhinitis.
      OBJECTIVES: The purpose of this study was to evaluate the long-term efficacy of
      sublingual immunotherapy. METHODS: One hundred thirty-seven patients with
      allergies to house dust mites were treated with sublingual house dust-mite
      specific immunotherapy for 2 or 3 years and were also observed for 3 years after
      discontinuation of the treatment. The patients were divided into 2 groups: group
      A (67 patients) received active treatment for 2 years and then 1 year for
      placebo, and group B (70 patients) received active treatment for 3 years. The
      success of the treatment was evaluated with the symptom score, skin prick test
      results, and the nasal allergen challenge score. RESULTS: According to our study
      results, we found a greater improvement in the 3 years of sublingual
      immunotherapy compared with the 2 years of sublingual immunotherapy when we
      looked at the comparative results of the total 6 years. CONCLUSION: We suggest 3
      years of sublingual immunotherapy for patients with perennial allergic rhinitis
      who require immunotherapy and do not accept the subcutaneous route of allergen
      administration.

PMID- 17545862
TI  - Does suture material and technique really matter? Lessons learned from 800
      consecutive blepharoplasties.
AB  - OBJECTIVES: The purpose of this study was to evaluate established suture
      materials and techniques for blepharoplasty closure and evaluate for any
      differences in rates of complications between these groups. STUDY DESIGN AND
      METHODS: This was a prospective study of a large sequential series of patients
      undergoing upper blepharoplasty who were treated by the same senior author over a
      5-year period. Patients were assigned one of four techniques for closure of the
      incision based on the senior author's experience. After 6 weeks, rates of
      complications and revisions were noted and addressed. Satisfaction rates were
      noted at 3 months. RESULTS: In the group whose incisions were closed with running
      subcuticular polypropylene (Prolene), 5 (2.5%) presented with milia, and 11
      (5.5%) had a standing cone deformity (SCD). Use of running cutaneous locked
      Prolene resulted in 8 patients (17%) with milia and 2 patients (4.4%) requiring
      revision of a SCD. Use of a running 6-0 plain gut suture resulted in 12 patients
      (6.7%) with milia and 5 patients (2.8%) with unsightly scarring. In the group
      whose incisions were closed with running 6-0 fast-absorbing gut, 10 patients (2%)
      presented with milia, and there were no scar revisions. There were statistically
      significant differences between the groups with respect to formation of milia,
      scarring, and persistent erythema (P < .008). CONCLUSIONS: Blepharoplasty is a
      safe and effective procedure that can be performed successfully with several
      established techniques. In our experience, closure with two interrupted 6-0
      Prolene sutures and a running 6-0 fast-absorbing gut resulted in the lowest rates
      of complications and revisions.

PMID- 17545863
TI  - Upper lateral cartilage-sparing component dorsal hump reduction in primary
      rhinoplasty.
AB  - BACKGROUND: Dorsal hump reduction is a critical step in rhinoplasty. Most of the
      reasons behind revisional procedures are related to incorrect hump reduction.
      METHODS: The authors used a modified dorsal hump reduction method in their
      primary cases, the steps of which are as follows: 1) dissection of the nasal
      vault; 2) bilateral submucoperichondrial dissections to free the cartilaginous
      septum; 3) separation of the upper lateral cartilages from the cartilaginous
      septum; 4) partial dissection of the upper lateral cartilages from the inner
      surfaces of the nasal bones bilaterally; 5) separation of the bony septum from
      the nasal bones bilaterally; 6) reduction of the partially isolated nasal bones;
      7) en bloc cartilaginous and bony septum removal. The authors have operated on 68
      primary cases over a 2 year period (30 mo). RESULTS: In the great majority of
      cases, the results were satisfactory. No revisions were performed in this patient
      group. CONCLUSIONS: This method is a good alternative to traditional techniques
      in noses with a high and narrow roof, thin skin, and weak middle nasal vault.
      Revision could be performed more easily when required. Initially, wide noses may
      not seem good candidates for this procedure; however, careful case-based
      preoperative planning may overcome this difficulty.

PMID- 17545864
TI  - Salvage surgery with free flap reconstruction: factors affecting outcome after
      treatment of recurrent head and neck squamous carcinoma.
AB  - OBJECTIVE: To determine factors predicting the outcome after salvage surgery with
      microvascular flap reconstruction for recurrent squamous cell cancer (SCC) of the
      head and neck. STUDY DESIGN: This is a retrospective analysis of patients treated
      at an academic medical center. METHODS: One hundred six patients underwent
      salvage surgery and microvascular flap reconstruction after prior unsuccessful
      cancer treatment using surgery, radiation, or chemotherapy. All patients had a
      follow-up interval after salvage surgery of at least 24 months unless cancer
      rerecurrence occurred within 24 months after salvage surgery. Factors including
      age, sex, comorbidity level, tobacco use, alcohol use, disease-free interval
      since prior therapy, prior radiation, prior chemotherapy, prior surgery,
      recurrent tumor T class, recurrent tumor N class, recurrent cancer stage, and
      tumor location were examined to determine their association with cancer
      rerecurrence after salvage surgery. Successful treatment was defined as patients
      who remained free from cancer rerecurrence for a minimum 2 year period after
      salvage surgery. RESULTS: Advanced recurrent T class (P = .02) was significantly
      associated with cancer recurrence. Recurrent cancer stage and patient smoking
      status approached statistical significance (P = .06). CONCLUSION: Patients with
      recurrent T1 and T2 class are the best candidates for salvage surgery and
      microvascular flap reconstruction for treatment of recurrent SCC of the head and
      neck. Patients with T3 and T4 class recurrent cancers and patients who continue
      to smoke after initial diagnosis and treatment of head and neck SCC are poor
      candidates to undergo salvage surgery.

PMID- 17545865
TI  - Virtual laryngoscopy: a noninvasive tool for the assessment of laryngeal tumor
      extent.
AB  - OBJECTIVES: Present a clinical application of virtual laryngoscopy (VL) in the
      assessment of laryngeal tumor and its extent. STUDY DESIGN: CT data from two
      subjects are acquired for this preliminary study. One subject is a healthy
      volunteer and the other is a patient with laryngeal tumor. The laryngeal
      framework and upper airway are reconstructed using CT data, which allows for
      computer-aided internal and external anatomical views and interactive fly
      through. METHODS: These CT data are reconstructed into 0.5 mm slice images,
      resulting in a total of 200-300 image slices. An advanced commercial
      visualization software (AMIRA) is used for 3D image segmentation, reconstruction
      and surface rendering of laryngeal anatomical structures. RESULTS: The 3D
      laryngeal framework and upper airway are reconstructed for both the tumor patient
      and the healthy subject. The conventional views of the reconstructed vocal folds
      are compared with those obtained from fiber-optic laryngoscope. Additionally,
      unique views of the vocal folds obtained from retrograde visualization and fly
      through are presented, which are not possible to obtain using conventional
      endoscope imaging. The segmented anatomical model and the tumor from the
      patient's CT images were displayed individually to show the distribution of the
      tumor and its extent as well as spatial and contextual relationships to the
      larynx and airway anatomical structures. CONCLUSIONS: This study demonstrated the
      potential application of VL as a noninvasive clinical diagnostic tool for the
      assessment of laryngeal tumor and its extent. Our preliminary results
      demonstrated that the VL may provide valuable insights for the diagnosis and
      treatment planning for laryngeal and airway tumors. The noninvasive VL may
      complement the invasive laryngoscopic examinations for the staging of tumors and
      follow-ups on surgical interventions.

PMID- 17545866
TI  - The ductal stretching technique: an endoscopic-assisted technique for removal of
      submandibular stones.
AB  - OBJECTIVE: The purpose of this study was to describe an innovative surgical
      technique for the removal of posterior and hilar stones of the submandibular
      salivary duct. METHODS: Between 1999 and 2005, 172 patients who had
      sialolithiasis of the submandibular duct were treated primarily by transoral
      incision and marsupialization of the duct and salivary gland. The ductal
      stretching technique involved endoscopic location of the stone, incision of the
      oral mucosa above the duct, isolation of the duct from the surrounding tissues,
      stretching of the duct, ductal incision above the calculus, sialolithotomy, and
      insertion of a drain. RESULTS: Forty-one patients with stones located in the
      posterior aspect of the duct were symptom-free and stone free after the
      procedure. One hundred and five patients with stones located in the hilum were
      treated with a success rate of 98%. Twenty-six patients with multiple stones in
      the hilar region were treated with a success rate of 81%. The overall success
      rate of the procedure was 96%. In 48 patients (28%), an additional undetected
      stone was diagnosed by endoscopy after the removal of the stone in the hilum. In
      62 patients (36%), strictures were diagnosed endoscopically posterior to the
      stone. Lingual nerve paresthesia occurred in one patient, who recovered
      completely. CONCLUSION: The ductal stretching technique is recommended as the
      procedure of choice in cases with posterior and hilar stones more than 5 mm in
      diameter to avoid surgical removal of the salivary gland.

PMID- 17545867
TI  - Equivalent noise level generated by drilling onto the ossicular chain as measured
      by laser Doppler vibrometry: a temporal bone study.
AB  - BACKGROUND: Inadvertent drilling on the ossicular chain is one of the causes of
      sensorineural hearing loss (HL) that may follow tympanomastoid surgery. A high
      frequency HL is most frequently observed. It is speculated that the HL is a
      result of vibration of the ossicular chain resembling acoustic noise trauma. It
      is generally considered that using a large cutting burr is more likely to cause
      damage than a small diamond burr. AIM: The aim was to investigate the equivalent
      noise level and its frequency characteristics generated by drilling onto the
      short process of the incus in fresh human temporal bones. METHODS AND MATERIALS:
      Five fresh cadaveric temporal bones were used. Stapes displacement was measured
      using laser Doppler vibrometry during short drilling episodes. Diamond and
      cutting burrs of different diameters were used. The effect of the drilling on
      stapes footplate displacement was compared with that generated by an acoustic
      signal. The equivalent noise level (dB sound pressure level equivalent [SPL eq])
      was thus calculated. RESULTS: The equivalent noise levels generated ranged from
      93 to 125 dB SPL eq. For a 1-mm cutting burr, the highest equivalent noise level
      was 108 dB SPL eq, whereas a 2.3-mm cutting burr produced a maximal level of 125
      dB SPL eq. Diamond burrs generated less noise than their cutting counterparts,
      with a 2.3-mm diamond burr producing a highest equivalent noise level of 102 dB
      SPL eq. The energy of the noise increased at the higher end of the frequency
      spectrum, with a 2.3-mm cutting burr producing a noise level of 105 dB SPL eq at
      1 kHz and 125 dB SPL eq at 8 kHz. In contrast, the same sized diamond burr
      produced 96 dB SPL eq at 1 kHz and 99 dB at 8 kHz. CONCLUSION: This study
      suggests that drilling on the ossicular chain can produce vibratory force that is
      analogous with noise levels known to produce acoustic trauma. For the same type
      of burr, the larger the diameter, the greater the vibratory force, and for the
      same size of burr, the cutting burr creates more vibratory force than the diamond
      burr. The cutting burr produces greater high-frequency than lower-frequency
      vibratory energy.

PMID- 17545868
TI  - Selective activation of cat primary auditory cortex by way of direct intraneural
      auditory nerve stimulation.
AB  - OBJECTIVES/HYPOTHESIS: Although cochlear implants have been successfully used by
      many individuals with profound hearing impairment, limitations still remain with
      this approach to hearing restoration, including poor stimulation selectivity
      because of cross-talk between electrodes and poor low-frequency percepts. These
      limitations may be mitigated by direct intraneural stimulation of the auditory
      nerve by way of an array of penetrating microelectrodes. Such an approach should
      provide focal stimulation and selective activation of the nerve fibers, thereby
      minimizing cross-talk among implanted stimulating electrodes and evoking narrow
      band frequency percepts. STUDY DESIGN: We investigated the activation of primary
      auditory cortex evoked by such direct intraneural electrical stimulation of the
      auditory nerve. METHODS: We implanted 11 penetrating microelectrodes in the cat
      auditory nerve, simulated the nerve by way of these electrodes, and recorded the
      evoked neuronal activity patterns in cat primary auditory cortex. We compared
      these activation patterns with acoustically evoked cortical activity patterns
      obtained in a different animal. RESULTS: Our results showed that direct
      stimulation of the auditory nerve evoked localized activity patterns in primary
      auditory cortex similar in spatial extent to those evoked by acoustic stimulation
      and that the extent of cortical activation by both acoustic and electrical
      stimuli was graded with stimulus intensity. These results suggest that the
      implanted electrodes can excite independent and small populations of nerve
      fibers. CONCLUSION: This study demonstrates the functional feasibility of direct
      intraneural auditory nerve stimulation with an array of penetrating
      microelectrodes and that such an approach could form the foundation for an
      auditory prosthesis with improved frequency coding.

PMID- 17545869
TI  - Cochlear implantation in the neurofibromatosis type 2 patient: long-term follow
      up.
AB  - OBJECTIVE: To evaluate the long-term hearing outcomes of neurofibromatosis type 2
      (NF2) patients with cochlear implants. METHODS: Retrospective analysis of
      cochlear implant performance in NF2 patients using open- and closed-set speech
      perception testing. RESULTS: Patients with NF2-associated bilateral vestibular
      schwannomas frequently become profoundly deaf. The aim of surgical resection
      should be to preserve serviceable hearing in at least one ear; however, this goal
      can be difficult to achieve. Frequently, tumor size or poor preoperative hearing
      status can require a surgical approach that leaves the patient with a profound,
      bilateral sensorineural hearing loss. If the cochlear nerve is preserved
      anatomically after vestibular schwannoma surgery, and if promontory stimulation
      confirms the functionality of the cochlear nerve, then cochlear implantation is
      an excellent option to restore hearing. We present six cochlear implant patients
      with NF2 who attained a significant improvement in open- and closed-set speech
      understanding with a mean follow-up of 7.9 (range: 5-13) years after surgery. In
      all but one case, the hearing results did not deteriorate over the follow-up
      period. CONCLUSION: Early surgical intervention for vestibular schwannomas in NF2
      patients when the cochlear nerve can be spared is an important consideration to
      allow for possible cochlear implantation. A 6- to 8-week recovery period for the
      anatomically intact cochlear nerve may be necessary to obtain a positive
      promontory stimulation response following tumor resection and should be performed
      prior to cochlear implantation.

PMID- 17545870
TI  - Outcome of endoscopic treatment of adult postintubation tracheal stenosis.
AB  - OBJECTIVES/HYPOTHESIS: To assess the results of primary endoscopic treatment of
      adult postintubation tracheal stenosis, to identify predictors of a successful
      outcome, and better define the scope and limitations of minimally-invasive
      surgery for this condition. METHODS: Sixty-two consecutive patients treated
      between April 2003 and 2006 with initial endoscopic surgery were prospectively
      studied. Patient and lesion characteristics, treatment details, complications,
      decannulation, and open surgery rates were recorded. Actuarial analysis and Cox
      regression were used to identify predictors of decannulation and freedom from
      external surgery. RESULTS: There were 34 male patients and the average age was 45
      +/- 16 years. The average stenosis height was 18 mm (range: 5-55 mm), and 82% of
      lesions were Myer-Cotton grades III or IV. Lesion height and intubation-to
      treatment latency independently predicted success of endoscopic surgery. Ninety
      six percent of patients with lesions <30 mm in height were treated
      endoscopically, but the success rate fell to 20% for lesions longer than 30 mm.
      Patients with recalcitrant lesions underwent airway augmentation (n = 11) or
      resection (n = 3), with a 79% success rate. All patients were decannulated, but
      some, predominantly morbidly obese patients, required long-term stents for
      dynamic airway compromise. Ninety-eight percent of re-interventions occurred
      within 6 months. CONCLUSIONS: Minimally invasive treatment is effective in
      postintubation airway stenosis and obviates the need for open cervicomediastinal
      surgery in most patients. Patients with old and long lesions are less likely to
      be cured endoscopically. For most patients in this subgroup, endoscopic surgery
      makes airway augmentation a viable, less invasive alternative to resection.
      Patients were unlikely to require further therapy after 6 months of symptom-free
      follow-up.

PMID- 17545871
TI  - Influence of age on the surgical outcome after endoscopic sinus surgery for
      chronic rhinosinusitis with nasal polyposis.
AB  - OBJECTIVES: To determine whether patient age is associated with the surgical
      outcome after endoscopic sinus surgery (ESS) with polypectomy. STUDY DESIGN: A
      prospective, controlled case series. MATERIALS AND METHODS: This study consisted
      of 60 patients who were diagnosed as having chronic rhinosinusitis (CRS) with
      nasal polyposis (NP) that was refractory to medical treatment. Three groups were
      classified according to patient age: pediatric (5-18 yr), adult (19-65 yr), and
      geriatric (over 65 yr). We collected 20 patients in each age group after applying
      the exclusion criteria. The extent of the polyps and the Lund-Mackay score were
      calculated for each patient, and they underwent ESS with polypectomy. We compared
      the objective endoscopic findings and subjective improvements in symptoms among
      the groups 6 months after the procedure. RESULTS: There were no statistical
      differences in polyp extent or Lund-Mackay score between the three age groups.
      The objective surgical outcome based on the endoscopic findings was worst in the
      pediatric group (45%), whereas the geriatric group showed the best results (90%).
      The differences in objective outcome among the three groups were significant, and
      patient age was a predictive variable for surgical result based on multiple
      logistic regression analysis. No major complications occurred, and the overall
      improvement in subjective symptoms was statistically significant in all three age
      groups at 6 months postoperatively. The subjective surgical outcome did not
      differ statistically between the groups, with the exception of olfactory
      disturbance. CONCLUSIONS: The results of the present study suggest that patient
      age influences the objective postoperative outcome in the endoscopic treatment of
      CRS with NP, and that ESS is an effective and reliable method for improving the
      subjective symptoms in patients of all age groups despite the statistically
      different objective surgical outcomes between the groups.

PMID- 17545872
TI  - Oropharyngeal foreign body after attempted nasal intubation: a case of traumatic
      middle turbinectomy.
AB  - A nasopharyngeal airway, or nasal trumpet, is an adjunctive airway device used to
      bypass upper airway obstruction at the level of the oral cavity or oropharynx.
      Although nasal trumpet placement on an awake patient may be uncomfortable, there
      are no reports of significant trauma from insertion. We present an unusual case
      of middle turbinate avulsion presenting as a foreign body in the oropharynx after
      several attempts at placement of a nasopharyngeal airway in an unconscious
      patient. We hope to raise awareness that nasal intubation in patients with
      altered consciousness can result in significant nasal trauma, especially after
      multiple attempts have failed.

PMID- 17545873
TI  - Adverse patient occurrences in otorhinolaryngology: results of a systematic
      registry in a tertiary referral hospital.
AB  - OBJECTIVE: To identify patient groups at risk for Adverse Patient Occurrences
      (APOs) to improve the quality of care. STUDY DESIGN: This study was conducted
      using retrospective analysis. METHODS: APOs have been systematically registered
      from 1997 to 2006 in all patients (6,932) admitted to the otorhinolaryngology
      head and neck surgery department of the University Hospital Maastricht, the
      Netherlands. Several characteristics such as length of stay, age, gender, season,
      and diagnosis were related to the incidence and type of APOs. RESULTS: Increasing
      age and length of stay are related to an increasing incidence of APOs. Children
      are found to be at high risk too and outpatient treatment (<24 h) is a risk
      factor for APOs. Of all APOs, 67% were organizational and 33% medical. The three
      diagnosis-related groups (DRGs), in which APOs occurred most, were the inner
      ear/cerebellopontine angle (CPA), esophagus, and head and neck oncology group. No
      seasonal influences on APO occurrences existed. CONCLUSIONS: Male and female
      patients >60 or <10 years old are at the highest risk for APOs. Their risk
      increases with their length of stay and is high when admitted less than 24 hours.
      When patients are among the three most prevalent DRGs, their risk is even higher.

PMID- 17545874
TI  - Stroboscopy versus high-speed glottography: a comparative study.
AB  - OBJECTIVES: To evaluate and to compare the diagnostic value of videostroboscopy
      (VS) and high-speed glottography (HGG) in dysphonic patients. STUDY DESIGN:
      Randomized, prospective study. METHODS: A total of 162 patients underwent
      indirect laryngoscopy using both methods (VS and HGG). The resulting 324 films
      were evaluated by two professionals (laryngologists, MDs) using a standardized
      protocol containing established criteria to classify vocal fold vibratory
      movement qualities. RESULTS: The rating "not assessable" was mentioned
      significantly more often in VS than in HGG (P < .001). In HGG, methodologic
      failures were less frequent, and the length of investigation was shorter. Even if
      the agreement between the two raters was higher in HGG (54%) compared with VS
      (42%), both percentage values show a low accordance in diagnostic findings.
      CONCLUSIONS: Regardless of the method used (VS or HGG), perceptive evaluations of
      vibratory movements of vocal folds revealed a higher variability than assumed.
      This result supports the need for objective methods to analyze vocal fold
      vibratory movements. Therefore, real-time imaging of vocal fold vibratory
      movements using HGG will be necessary.

PMID- 17545875
TI  - In reference to temporal bone imaging in GJB2 deafness.

PMID- 17545877
TI  - Pulmonary embolism in an adolescent soccer player: a case report.
AB  - Pulmonary emboli are potentially life threatening and are rare in the young,
      healthy, athletic population. We describe the presentation of pulmonary emboli in
      an otherwise healthy athlete; this has not been reported previously in the
      literature. A 16-yr-old male soccer player with no apparent risk factors
      presented in distress with bilateral pulmonary emboli. An extensive workup did
      not reveal a cause for this phenomenon. The patient was anticoagulated, and a
      Greenfield inferior vena cava filter was placed because of recurrent symptoms and
      poor compliance with anticoagulation. This case report illustrates the importance
      of considering pulmonary embolism as a diagnosis in athletes who present with
      sudden onset of dyspnea with no discernable cause. Greenfield filter placement in
      the management of these cases remains controversial.

PMID- 17545878
TI  - Recurrent concussion and risk of depression in retired professional football
      players.
AB  - PURPOSE: The purpose of our study was to investigate the association between
      prior head injury and the likelihood of being diagnosed with clinical depression
      among retired professional football players with prior head injury exposure.
      METHODS: A general health questionnaire, including information about prior
      injuries, the SF-36 (Short Form 36), and other markers for depression, was
      completed by 2552 retired professional football players with an average age of
      53.8 (+/-13.4) yr and an average professional football-playing career of 6.6 (+/
      3.6) yr. A second questionnaire focusing on mild cognitive impairment (MCI)
      related issues was completed by a subset of 758 retired professional football
      players (50 yr and older). RESULTS: Two hundred sixty-nine (11.1%) of all
      respondents reported having prior or current diagnosis of clinical depression.
      There was an association between recurrent concussion and diagnosis of lifetime
      depression (chi2=71.21, df=2, P<0.005), suggesting that the prevalence increases
      with increasing concussion history. Compared with retired players with no history
      of concussion, retired players reporting three or more previous concussions
      (24.4%) were three times more likely to be diagnosed with depression; those with
      a history of one or two previous concussions (36.3%) were 1.5 times more likely
      to be diagnosed with depression. The analyses controlled for age, number of years
      since retirement, number of years played, physical component score on the SF-36,
      and diagnosed comorbidities such as osteoarthritis, coronary heart disease,
      stroke, cancer, and diabetes. CONCLUSION: Our findings suggest a possible link
      between recurrent sport-related concussion and increased risk of clinical
      depression. The findings emphasize the importance of understanding potential
      neurological consequences of recurrent concussion.

PMID- 17545879
TI  - Quadratus lumborum asymmetry and L4 pars injury in fast bowlers: a prospective MR
      study.
AB  - PURPOSE: This prospective study examined the association between quadratus
      lumborum (QL) asymmetry and the development of symptomatic pars interarticularis
      lesions in the lumbar spine of adolescent cricket fast bowlers. METHODS: Annual
      magnetic resonance imaging was used to measure QL volume asymmetry and for
      identifying pars lesions of the lumbar vertebrae in fast bowlers (N=51) and a
      control group of swimmers (N=18). Manual segmentation of axial images spanning
      the lumbar spine was performed to calculate percent QL asymmetry relative to the
      bowling- or throwing- (swimmers) arm side. Asymmetry above 100% indicated a
      larger QL volume on the bowling- (throwing) arm side. RESULTS: The mean QL
      asymmetry in bowlers of 110.5% (SD=12.1%) was significantly different from the
      96.6% (SD=5.0%) asymmetry in swimmers (t=6.75, P<or=0.001). In bowlers with
      symptomatic unilateral L4 pars lesions (N=11), which all developed opposite the
      bowling-arm side, the mean 124.3% (SD=8.3%) QL asymmetry exceeded the 106.7%
      (SD=10.1%) asymmetry in bowlers without these one-sided lesions. A logistic
      regression model (intercept=-22.1, P<or=0.001; asymmetry coefficient=0.18,
      P<or=0.001) demonstrated a significant association between increasing QL
      asymmetry and L4 lesions in bowlers. Receiver operating characteristic curve
      analysis demonstrated that QL asymmetry was an excellent predictor of L4 lesions
      in fast bowlers (area under curve=0.89, 95% confidence interval: 0.79, 0.98).
      CONCLUSION: The strong association between QL asymmetry and the development of
      symptomatic unilateral L4 pars lesions in adolescent bowlers conceivably reflects
      a mechanical coupling between the loading milieu generating these injuries and
      preferential hypertrophy of this paraspinal muscle in response to repetitive
      activation during fast bowling.

PMID- 17545880
TI  - Cycling efficiency is not compromised for moderate exercise in moderately severe
      COPD.
AB  - INTRODUCTION/PURPOSE: Hyperpnea and hyperinflation have been proposed as
      contributors to exaggerated energy demands in chronic obstructive pulmonary
      disease (COPD), yet there are incomplete data on exercise requirements. This
      study compared total-body energy demands of the internal (unloaded) and external
      work of cycling and delta mechanical efficiency in 40 patients (FEV1: 36+/-14%
      predicted) with COPD and 28 healthy age-matched controls while characterizing
      dynamic hyperinflation. METHODS: Steady-state V O2 was obtained at rest, during
      unloaded and 20-W cycling, and at 20, 50, and 65% peak cycling power. Delta
      mechanical efficiency was calculated between constant-load cycling at 65 and 20%
      peak power. Dynamic hyperinflation was assessed from inspiratory capacity
      maneuvers. RESULTS: Oxygen demands (L.min) at rest, for internal work (0.47+/
      0.14 vs 0.45+/-0.11) or external work at 20 W (0.62+/-0.20 vs 0.57+/-0.13), were
      not different between patients and controls, although ventilation was elevated in
      COPD. Cycling at 65% of peak power induced dynamic hyperinflation in COPD, which
      indices were not related to cycling efficiency. Delta efficiency (%) was not
      different between patients (26.3+/-8.1) and controls (24.8+/-4.0). CONCLUSION:
      Findings suggest that bioenergetics of submaximal cycling is not compromised in
      moderately severe COPD despite tachypnea and dynamic hyperinflation.

PMID- 17545881
TI  - Effects of exercise in overweight Japanese with multiple cardiovascular risk
      factors.
AB  - PURPOSE: The effects of exercise in subjects with multiple cardiovascular risk
      factors (RF) have never been tested in a large-scale randomized controlled trial.
      The favorable results from our observational study led to this randomized
      controlled trial. METHODS: The participants, recruited from a community, were
      overweight, with two of the following three risk factors: hypertension,
      hyperlipidemia, or glucose intolerance (N=561; 44% male; mean age (SD) 67 (6);
      mean BMI 26.4 (2.0)). All participants received a standard health exam with
      counseling, followed by randomization. The intervention group (INT) was to
      exercise two to four times per week for 6 months at a fitness club. RESULTS:
      Dropout rate was 11% for INT and 10% for the controls. INT exercised an average
      of 2.6 times per week. Among primary outcome measures, there was a marginally
      significant between-group difference in changes in systolic blood pressure
      (intervention minus control, -2.46 mm Hg). Reductions in LDL cholesterol (-1.9
      mg.dL) and hemoglobin A1c (-0.042%) were not significant. Among secondary
      outcomes, between-group differences were significantly greater (P<0.05) for INT
      in mean body weight (-1.60 kg), waist circumference (-1.8 cm), triglyceride (-7
      mg.dL), hsCRP (-0.063 mg.L), and estimated VO2peak (2.0 mL.kg.min). All
      directional mean RF changes consistently favored INT. A cardiovascular risk
      reduction estimated from the changes in RF was about 24%. A greater improvement
      was also found in health-related quality-of-life measures (SF-36) in INT. No
      difference was found in the adverse event rate. CONCLUSIONS: Exercising an
      average of 2.6 times per week for 6 months produced a significant improvement in
      cardiovascular risk profile in subjects with multiple cardiovascular risk factors
      through cumulative results of modest yet pervasive changes in all conventional
      risk factors, without increased adverse effects.

PMID- 17545882
TI  - Dietary apple polyphenols enhance gastrocnemius function in Wistar rats.
AB  - PURPOSE: Green tea polyphenols have been reported to improve muscle function in
      dystrophic mice. The chemical structure of apple polyphenols (APP) is similar to
      that of tea polyphenols; however, their effects on muscle function have not been
      examined previously. We examined the effects of dietary intake of APP on
      gastrocnemius function in Wistar rats. METHODS: Sixteen male rats (11 wk old)
      were divided into two groups: the 4.8% APP diet group and the control group (N=8
      in each group). Before and after 3 wk of treatment, right-leg tetanic ankle
      torques were measured. Successive twitch torques (four sessions per minute for 2
      min) were also measured to test indications of fatigue. Contralateral (left) legs
      were used for wet weight measurement and examination of mRNA expression. RESULTS:
      Total-body and muscle weights were similar in both the groups. The adipose tissue
      weight of the APP group was significantly lower than that of the control group
      (P<0.05). The isometric torque of the APP group was significantly higher than
      that of the control group (P<0.05). During the 2-min experimental period, the
      relative twitch torques (compared with the initial value) of the APP group were
      larger than those of the control group. Statistical significance was observed at
      90, 105, and 120 s (P<0.05). Expression of peroxisome proliferator-activated
      receptors alpha and delta--positive regulators of lipid oxidation--were
      significantly higher in the APP group than in the control group (P<0.05).
      CONCLUSION: We conclude that dietary APP enhance normal muscle function in Wistar
      rats. Alteration of lipid metabolism might be one of the mechanisms of this
      phenomenon.

PMID- 17545883
TI  - Neuroendocrine responses to an acute bout of eccentric-enhanced resistance
      exercise.
AB  - PURPOSE: The purpose of this study was to compare the total testosterone (TT),
      bioavailable testosterone (BT), growth hormone (GH), lactate, and ratings of
      perceived exertion (RPE) responses between a single bout of traditional (TRAD)
      and eccentric-enhanced resistance exercise (ECC+) of matched training volumes.
      METHODS: Twenty-two previously untrained males (21.9+/-0.8 yr) completed one
      familiarization and one baseline 1RM testing bout, for the bench press and squat
      exercises, and then two exercise bouts. During exercise bout 1, all subjects
      completed a TRAD protocol (four sets of six reps at 52.5% 1RM), and the
      subsequent exercise bout consisted of either a TRAD or an ECC+ protocol (three
      sets of six reps at 40% 1RM concentric and 100% 1RM eccentric) for the bench
      press and squat exercises. Blood samples acquired at rest, immediately after
      (T1), and 15, 30, 45, and 60 min after exercise were assessed for serum TT, BT,
      GH, and blood lactate concentrations. RESULTS: Resting and postexercise TT, BT,
      and GH were not significantly different between groups. Postexercise TT was not
      elevated during either bout or in either group, whereas BT increased 15-16% at T1
      in both groups during bout 2. Postexercise GH concentrations were elevated 500
      7000% above baseline after both protocols. Postexercise lactate accumulation and
      RPE were greater with ECC+ than TRAD. CONCLUSION: TRAD and ECC+ show similar
      neuroendocrine and differing metabolic responses during the early phase of
      resistance exercise in untrained, college-age men.

PMID- 17545884
TI  - Neuromuscular fatigue during sustained contractions performed in short-term
      hypoxia.
AB  - PURPOSE: Hypoxia is known to change neuronal activity in vitro and to impair
      performance in vivo. The present study was designed to study neuromuscular
      fatigue in acute hypoxia, and we hypothesized that hypoxia results in additional
      fatigue during sustained contractions, presumably because of increased central
      fatigue. METHODS: Twelve healthy subjects participated in a normoxic (NX) and
      hypoxic (HX) experiment performed on separate days. Hypoxia was induced by
      breathing an HX air mixture containing 12% oxygen. Before, during, and after a 90
      s sustained voluntary maximal contraction (MVC) of the first dorsal interosseus
      muscle, we measured force, voluntary activation (VA), and parameters of motor
      cortical excitability (motor-evoked potentials (MEP) and silent periods (SP)).
      Measures of peripheral nerve and muscle function, compound motor action potential
      (M-wave), and muscle twitch forces were also taken. RESULTS: During the MVC,
      force declined similarly during both HX and NX. VA decreased throughout the
      contraction in HX, but, surprisingly, this decrease in VA in HX did not exceed
      that observed in NX. Also, motor cortical excitability changed to a similar
      degree in HX and NX; that is, MEP amplitude and SP duration increased. M-wave
      amplitude decreased significantly during the sustained MVC in NX and HX. The only
      difference observed between NX and HX was the quicker recovery of the muscle
      twitch in HX, which was even potentiated after 5 min of recovery. CONCLUSION: The
      present results show that peripheral and central neuromuscular adaptations during
      a sustained fatiguing contraction are similar in NX and HX. The quicker recovery
      and potentiation of twitch forces in HX suggest alterations in myosin
      phosphorylation, which may enhance contractile force.

PMID- 17545885
TI  - Indoor climbing elicits plasma oxidative stress.
AB  - PURPOSE: Indoor climbing is a worldwide sport with particular physiological and
      physical demands. The purpose of this study was to analyze the effect of
      sustained indoor climbing until exhaustion on plasma oxidative stress markers,
      and to relate it to whole-body dynamic exercise performed at the same percentage
      of maximal oxygen uptake (VO2max). METHODS: Fourteen male indoor climbers
      continuously climbed a competition-style route until exhaustion. Oxygen
      consumption and heart rate were continuously monitored during the climbing
      exercise. One week later, subjects performed a treadmill running protocol with
      the same duration and percentage of VO2max as that of climbing exercise. Blood
      samples were collected at rest, immediately after, and 1 h after both exercise
      protocols to analyze plasma levels of reduced (GSH) and oxidized (GSSG)
      glutathione, malondialdehyde (MDA), protein sulfhydryl (-SH) and carbonyl (CG)
      groups, total antioxidant status (TAS) and uric acid (UA), and total blood
      leukocytes, neutrophil, and lymphocyte counts. RESULTS: Compared with running,
      climbing significantly increased the %GSSG, MDA, CG, TAS, and UA and decreased
      the GSH and -SH content. Blood counts of total leukocytes and neutrophils
      increased immediately after and 1 h after both running and climbing (P<0.05),
      although counts were higher in climbing than in running (P<0.05). Lymphocytes
      significantly increased from baseline to 0 h, although they decreased below
      baseline 1 h after climbing (P<0.05). CONCLUSION: Data demonstrate that indoor
      climbing induces plasma oxidative stress. Moreover, results suggest that an
      ischemia-reperfusion prooxidant-based mechanism related to climbers' sustained
      and intermittent isometric forearm muscle contractions might have significantly
      contributed to observed plasma oxidative stress.

PMID- 17545886
TI  - Cytokine and oxidative responses to maximal cycling exercise in sedentary
      subjects.
AB  - INTRODUCTION: The simultaneous determination of the time course and magnitude of
      oxidative stress indicators and cytokine changes elicited by maximal incremental
      exercise has not yet been published for healthy sedentary subjects. PURPOSE: The
      determination of normal exercise-induced changes in oxidant-antioxidant status
      and plasma cytokine represents a fundamental step before exploring patients
      suspected of altered biochemical responses. METHODS: Fifteen healthy sedentary
      subjects performed an incremental cycle exercise until volitional exhaustion with
      measurement of maximal oxygen uptake (VO2max), two cytokines (IL-6 and TNF
      alpha), and three indicators of oxidative stress (plasma thiobarbituric acid
      reactive substances (TBARS), reduced erythrocyte glutathione (GSH), and reduced
      plasma ascorbic acid (RAA)). RESULTS: At VO2max, we noted a significant increase
      in plasma IL-6 and TNF-alpha concentrations, concomitant with the decrease in
      plasma RAA level. Besides, the plasma TBARS increase and erythrocyte GSH decrease
      respectively occurred at the 5th and 10th minutes of recovery. The exercise
      induced variations of all blood indicators were completed within the 20th minute
      of the recovery period. We found significant positive correlations between VO2max
      and the peak increases in IL-6 (but not TNF-alpha) and TBARS. The corresponding
      variations of IL-6 and TBARS were also correlated. CONCLUSION: This study
      indicates that blood samples for analyses of changes in both oxidant-antioxidant
      status and cytokine levels in response to maximal cycling exercise must be
      performed within the first 20 min of the postexercise recovery period.

PMID- 17545887
TI  - Peak cardiorespiratory responses during aquatic and land treadmill exercise.
AB  - PURPOSE: Aquatic treadmill exercise has traditionally been used for aerobic
      training during rehabilitation; however, its ability to elicit comparable
      cardiorespiratory stress compared with land exercise is unclear. The purpose of
      this study was to investigate the cardiorespiratory (CR) responses elicited
      during maximal-effort protocols using an aquatic treadmill (ATM) and a land
      treadmill (TM). METHODS: Twenty-three college runners participated in two
      continuous, incremental peak oxygen consumption protocols (ATM and TM) until
      volitional exhaustion. For the ATM protocol, subjects were submerged in 28
      degrees C water to the xiphoid process. ATM speed was increased incrementally to
      206.8+/-23.1 m.min, and water jet resistance was increased 10% every minute
      thereafter. For the TM protocol, speed was increased to 205.3+/-22.3 m.min, and
      grade was increased 2% every minute thereafter. Rest between sessions was at
      least 48 h. Oxygen consumption (VO2), heart rate (HR), minute ventilation (VE),
      tidal volume (VT), breathing frequency (f), and respiratory exchange ratio (RER)
      were measured continuously, with peak values used for analysis. Rating of
      perceived exertion (RPE) was recorded immediately after each test, and blood
      lactate (LA) was measured 3 min afterward. RESULTS: VE and f were significantly
      greater in ATM versus TM; however, VO2, HR, VT, RER, LA, RPE, speed, and exercise
      times were similar for both protocols. CONCLUSIONS: Despite differences in VE and
      f, it seems that the fluid resistance created by water and jets in an ATM elicits
      peak CR responses comparable with those seen with inclined TM. These findings
      suggest that ATM running may be as effective as TM running for aerobic
      conditioning in fit individuals.

PMID- 17545888
TI  - Dehydration impairs vigilance-related attention in male basketball players.
AB  - PURPOSE: To determine the effects of dehydration (DEH) on attentional vigilance
      in male basketball players. METHODS: The Test of Variables of Attention (TOVA;
      Universal Attention Disorders) was administered to 11 male basketball players (17
      28 yr) at baseline (test 1), after walking (50% V O2max) in the heat (40 degrees
      C and 20% relative humidity) (test 2), and then after a simulated basketball game
      (test 3). Tests 2 and 3 were performed while subjects were either DEH (1-4%) or
      euhydrated (EUH). The TOVA consisted of target-infrequent and target-frequent
      conditions, simulating static and dynamic (such as a basketball game)
      environments, respectively. TOVA measures included errors of omission (OE) and
      commission (CE), response time (RT), and sensitivity. RESULTS: During the target
      infrequent half of test 3, EUH resulted in significantly better sensitivity
      (+0.4+/-1.2 vs -0.9+/-1.3), faster RT (-8+/-20 vs +16+/-28), and fewer OE (-0.4+/
      0.7 vs +1.3+/-2.4) compared with DEH. During the target-frequent half, EUH
      resulted in significantly fewer OE (-4+/-15 vs +5+/-7) and CE (-1.9+/-3.2 vs
      0.6+/-1.4) in test 2 and greater sensitivity (+0.7+/-2.6 vs -0.7+/-1.1) and
      faster RT (-21+/-28 vs +5+/-31) than DEH in test 3. CONCLUSION: Vigilance-related
      attention of male basketball players was impaired by DEH, especially during the
      target-frequent condition of the TOVA. These results suggest that fluid
      replacement is essential to prevent the decline in vigilance that occurs with DEH
      in highly dynamic environments. Therefore, basketball players should be advised
      to maintain EUH for optimal concentration and attentional skills during
      competition.

PMID- 17545889
TI  - Validation of bioimpedance spectroscopy to assess acute changes in hydration
      status.
AB  - PURPOSE: To validate bioimpedance spectroscopy (BIS) as a field method for
      measuring small, acute changes in extracellular water (ECW) during a fluid
      fast/rehydration manipulation. METHODS: Seventeen young adults (15 female, 2
      male) participated in a 4-d fluid fast/rehydration protocol designed to induce
      acute changes in ECW. ECW change (DeltaECW), measured by bioimpedance
      spectroscopy (BIS-DeltaECW), was compared with DeltaECW, measured by bromide
      dilution (Br-DeltaECW), and change in body weight (DeltaBW). RESULTS: Regardless
      of hydration status, BIS-DeltaECW and Br-DeltaECW were similar; during
      dehydration, the mean difference between these two methods was 0.16 kg (P=0.61),
      and during rehydration, the mean difference was 0.58 kg (P=0.06). Assuming that
      DeltaECW=DeltaBW, DeltaECW as estimated from DeltaBW differed significantly from
      Br-DeltaECW, but not from BIS-DeltaECW. In addition, BIS-DeltaECW correlated
      significantly with DeltaBW (r=0.57 and 0.65 during dehydration and rehydration,
      respectively). However, the magnitude of DeltaECW impacted the accuracy of BIS
      DeltaECW because BIS measures tended to overestimate DeltaECW at values between
      0.0 and 1.0 kg and to underestimate changes at values above 1.0 kg. CONCLUSION:
      These findings suggest that BIS provides an accurate estimate of DeltaECW
      compared with bromide dilution during short-term changes in hydration.

PMID- 17545890
TI  - Effect of pedaling technique on mechanical effectiveness and efficiency in
      cyclists.
AB  - PURPOSE: To optimize endurance cycling performance, it is important to maximize
      efficiency. Power-measuring cranks and force-sensing pedals can be used to
      determine the mechanical effectiveness of cycling. From both a coaching and basic
      science perspective, it is of interest if a mechanically effective pedaling
      technique leads to greater efficiency. Thus, the purpose of this study was to
      determine the effect of different pedaling techniques on mechanical effectiveness
      and gross efficiency during steady-state cycling. METHODS: Eight male cyclists
      exercised on a cycle ergometer at 90 rpm and 200 W using four different pedaling
      techniques: preferred pedaling; pedaling in circles; emphasizing the pull during
      the upstroke; and emphasizing the push during the downstroke. Each exercise bout
      lasted 6 min and was interspersed with 6 min of passive rest. We obtained
      mechanical effectiveness and gross efficiency using pedal-reaction forces and
      respiratory measures, respectively. RESULTS: When the participants were
      instructed to pull on the pedal during the upstroke, mechanical effectiveness was
      greater (index of force effectiveness=62.4+/-9.8%) and gross efficiency was lower
      (gross efficiency=19.0+/-0.7%) compared with the other pedaling conditions (index
      of force effectiveness=48.2+/-5.1% and gross efficiency=20.2+/-0.6%; means and
      standard deviations collapsed across preferred, circling, and pushing
      conditions). Mechanical effectiveness and gross efficiency during the circling
      and pushing conditions did not differ significantly from the preferred pedaling
      condition. CONCLUSIONS: Mechanical effectiveness is not indicative of gross
      efficiency across pedaling techniques. These results thereby provide coaches and
      athletes with useful information for interpreting measures of mechanical
      effectiveness.

PMID- 17545891
TI  - Power versus strength-power jump squat training: influence on the load-power
      relationship.
AB  - PURPOSE: The purpose of this investigation was to compare the impact of power
      training and strength-power training on the load-power relationship in the jump
      squat. METHODS: Twenty-six recreationally trained male subjects were randomly
      assigned to either a power training group (P; N=10), a strength-power training
      group (SP; N=8), or a control group (C; N=8). The P group trained for 12 wk,
      performing seven sets of six jump squats with the optimal load for maximal power
      output (body mass only, no external load), whereas the SP group performed five
      sets of six jump squats with the optimal load for maximal power output (body mass
      only, no external load) and three sets of three squats with 90% of their one
      repetition maximum (1RM). Work performed by the P and SP subjects was equivalent
      throughout the 12 wk of training. Peak power relative to body mass (PP), jump
      height (JH), peak force relative to body mass (PF), and peak velocity (PV) during
      the jump squat were examined across loads of body mass (BM) and 20, 40, 60, and
      80 kg at week 0 (baseline) and after weeks 6 (midtest) and 12 (posttest).
      RESULTS: After training, the P group significantly increased PP at BM and 20 kg,
      whereas the SP group significantly increased PP output across all loading
      conditions. Similarly, jump height was significantly increased by the P group at
      the lighter loads (BM, 20 kg, and 40 kg) and by the SP group at all loads.
      Whereas significant improvements in maximal power output and jump height at BM
      were observed in both P and SP groups, no difference in maximal power output or
      maximal jump height existed between the training groups. CONCLUSION: Combined
      lower-body strength-power training is effective as power training for improving
      maximum jump height and maximum power output in the jump squat, and it is more
      effective than power training at producing all-around (i.e., from BM to 80 kg)
      improvements in the load-power relationship of the jump squat.

PMID- 17545892
TI  - Supplemental feedings increase self-selected work output during wildfire
      suppression.
AB  - PURPOSE: The purpose of this study was to determine the impact of supplemental
      feeding strategies on self-selected activity during wildland fire suppression.
      METHODS: Seventy-six wildland firefighters were studied in three experiments for
      three fire seasons. During the first two seasons, subjects consumed, in addition
      to their sack lunch, 1) liquid carbohydrate (CHO) (200 mL.h, 20% CHO (40 g.h, 160
      kcal.h)) or placebo (PLA) every hour, or 2) liquid CHO (200 mL.h, 20% CHO (40
      g.h, 160 kcal.h) every even hour and solid CHO (25 g of CHO, 10 g of protein, 2 g
      of fat, and 160 kcal.h) every odd hour, or PLA, using counterbalanced crossover
      designs. During the third season, subjects consumed their sack lunch halfway
      through their workday, or shift food items of approximately 150-400 kcal at 90
      min intervals after breakfast in a randomized crossover design (isocaloric
      intake, 1534+/-265 kcal per workday). Work output was monitored using CSA and
      MiniMitter actigraphy units. RESULTS: During the liquid CHO trials, subjects
      consuming CHO demonstrated significantly higher average activity counts
      throughout the day compared with PLA (50,262+/-36,560 and 40,159+/-35,969 counts
      per hour for 12 h for the CHO and PLA trials, respectively; P<0.05). For the
      liquid+solid CHO trials, subjects consuming CHO demonstrated higher average
      activity counts per minute 2 h before lunch and the last 4 h of the workday
      compared with PLA (P<0.05). For the sack lunch and shift food trials, subjects
      consuming shift foods demonstrated higher average counts per minute during the
      final 2 h compared with those consuming sack lunch (521+/-421 vs 366+/-249 counts
      per minute during 2 h; P<0.05). CONCLUSION: Liquid and/or solid supplemental CHO
      and regular feedings increased self-selected work rates during wildland fire
      suppression, particularly during the latter hours of the workday.

PMID- 17545893
TI  - Allometric scaling of biceps strength before and after resistance training in
      men.
AB  - PURPOSE: The purposes of this study were 1) derive allometric scaling models of
      isometric biceps muscle strength using pretraining body mass (BM) and muscle
      cross-sectional area (CSA) as scaling variables in adult males, 2) test model
      appropriateness using regression diagnostics, and 3) cross-validate the models
      before and after 12 wk of resistance training. METHODS: A subset of FAMuSS
      (Functional SNP Associated with Muscle Size and Strength) study data (N=136) were
      randomly split into two groups (A and B). Allometric scaling models using
      pretraining BM and CSA were derived and tested for group A. The scaling exponents
      determined from these models were then applied to and tested on group B
      pretraining data. Finally, these scaling exponents were applied to and tested on
      group A and B posttraining data. RESULTS: BM and CSA models produced scaling
      exponents of 0.64 and 0.71, respectively. Regression diagnostics determined both
      models to be appropriate. Cross-validation of the models to group B showed that
      the BM model, but not the CSA model, was appropriate. Removal of the largest six
      subjects (CSA>30 cm) from group B resulted in an appropriate fit for the CSA
      model. Application of the models to group A posttraining data showed that both
      models were appropriate, but only the body mass model was successful for group B.
      CONCLUSION: These data suggest that the application of scaling exponents of 0.64
      and 0.71, using BM and CSA, respectively, are appropriate for scaling isometric
      biceps strength in adult males. However, the scaling exponent using CSA may not
      be appropriate for individuals with biceps CSA>30 cm. Finally, 12 wk of
      resistance training does not alter the relationship between BM, CSA, and muscular
      strength as assessed by allometric scaling.

PMID- 17545894
TI  - Objective assessment of activity in older adults at risk for mobility disability.
AB  - PURPOSE: The purpose of this study was to evaluate the validity of three
      objective measures of physical activity (Accusplit Eagle 120 mechanical pedometer
      (AE120), NL-2000 electronic pedometer, and IDEEA pattern-recognition device) that
      varied in their levels of sophistication, among older adults at risk for mobility
      disability. In addition, we examined the potential influences of gait speed and
      body mass index (BMI) on step count accuracy. METHODS: Step counts recorded on
      the three devices were compared against manual step counts made by two
      investigators as each participant walked 131 m around an indoor track at their
      preferred walking speed (N=29; 75.8+/-4.2 yr). Gait speed was determined by
      dividing total distance walked by time to completion. BMI was calculated from
      height and body mass measurements. RESULTS: All three devices significantly
      underestimated steps taken (AE120=22.8+/-53.9 steps; NL-2000=4.0+/-5.8 steps;
      IDEEA=5.6+/-7.8 steps), but there was no significant difference between devices
      (P=0.084). Steps counted by the AE120, NL-2000, and IDEEA were significantly
      correlated with manual step counts (r=0.508, 0.980, and 0.965, respectively;
      P<or=0.005). However, the AE120 was not clinically acceptable, sharing only 26%
      common variance with actual steps taken. The accuracy of the three devices was
      not influenced systematically by either gait speed or BMI. CONCLUSION: Our data
      show that the AE120 is a poor choice for measuring physical activity in older
      adults at risk for mobility disability. Both the NL-2000 and IDEEA devices have
      acceptable measurement qualities; however, the NL-2000 is the more practical of
      the two for use in either research or clinical practice.

PMID- 17545895
TI  - It takes a team.

PMID- 17545896
TI  - How to control pain and improve functionality after total joint replacement
      surgery.

PMID- 17545897
TI  - Cultural competency benefits patients, therapists.

PMID- 17545898
TI  - Improve your assessment of bilingual clients with communication disorders.

PMID- 17545899
TI  - Biomechanical comparison of C1-C2 posterior arthrodesis techniques.
AB  - STUDY DESIGN: Biomechanical comparison of 5 atlantoaxial posterior arthrodesis
      techniques. OBJECTIVE: To assess the relative value of different posterior wire
      constructs when one or two transarticular screws are used. SUMMARY OF BACKGROUND
      DATA: A combination of Gallie or Brooks techniques and 2 posterior transarticular
      screws has been shown to be effective for atlantoaxial arthrodesis. Anatomic
      constraints may preclude the insertion of a transarticular screw unilaterally or
      bilaterally. METHODS: Ten adult human cadaveric upper cervical spine specimens
      were used. The specimens were tested intact, after odontoidectomy and transverse
      and capsular ligament section and after stabilization with each of the 5
      techniques: Brooks-Jenkins cable fixation, Brooks-Jenkins with unilateral
      transarticular screw, Gallie posterior wire construct with unilateral
      transarticular screw, Brooks-Jenkins with bilateral screws, and Gallie with
      bilateral screws. Pure moments were applied in flexion-extension, lateral
      bending, and torsion within physiologic limits (<1.5 Nm). RESULTS: In flexion
      extension and lateral bending, the range of motion (ROM) and neutral zone (NZ)
      increased significantly after the specimens were injured as compared with intact
      spines (P < 0.001). After stabilization, the ROM and NZ were significantly lower
      than in injured and intact spines in all motions (P < 0.01) except lateral
      bending in the intact spine. Among the 5 instrumented techniques, the ROM for the
      Gallie construct with 1 screw was significantly higher than for the Brooks
      Jenkins construct with 1 or 2 screws in flexion-extension (P < 0.05). In axial
      torsion, the Gallie construct with 1 screw displayed a larger NZ and ROM than any
      of the other 4 constructs (P < 0.05). CONCLUSIONS: Gallie or Brooks-Jenkins cable
      fixation alone may not be adequate for atlantoaxial arthrodesis. If 2
      supplemented transarticular screws can beinserted, there is no difference between
      the Gallie or Brooks techniques. If only a single screw can be inserted, the
      Brooks-Jenkins technique is recommended rather than a Gallie technique.

PMID- 17545900
TI  - Short-term comparison of cervical fusion with static and dynamic plating using
      computerized motion analysis.
AB  - STUDY DESIGN: This study is a retrospective review of fusion rates for cervical
      plates, analyzed by means of computerized analysis. OBJECTIVES: This study
      compares the fusion rates for two-level anterior cervical discectomy and fusion
      between patients with static versus dynamic plates. SUMMARY OF BACKGROUND DATA:
      Anterior cervical plating has been shown to decrease the pseudarthrosis rate.
      However, static plates, which have been successful in reducing nonunion rates,
      may be "too rigid" in certain situations, leading to pseudarthrosis in some
      patients. Recently, some surgeons have begun using dynamic plate constructs to
      avoid this problem. METHODS: A retrospective review was performed of patients
      having a two-level anterior cervical discectomy and fusion performed either with
      a static or dynamic plate. A computerized method for evaluating the presence of a
      solid fusion was used with a criterion of <2 degrees of motion considered a solid
      fusion. RESULTS: The follow-up time period averaged 10 months (range, 5.8-13
      months) for the static plate group and 9.5 months (range, 5.8-13 months) for the
      dynamic plate group. Based on a motion threshold of 2 degrees, the rate of fusion
      per level for patients in the static plate/autograft group was 87.8%, resulting
      in an overall fusion rate of 76.2%. The rate for fusion per level for patients
      treated with a dynamic plate and allograft was 89.8%, with an overall fusion rate
      of 81.8%. There was no statistically significant difference between the two
      groups (P = 0.469). The fusion rate increased during the follow-up period: In the
      6- to 9-month interval, the static plate/autograft group had a 62.5% fusion rate,
      versus 75% for the dynamic plate/allograft group. In the 10- to 13-month
      interval, the fusion rate had increased to 84.7% for the static plate/autograft
      group and 90% for the dynamic plate/allograft group. CONCLUSIONS: Computerized
      evaluation of digitized films can improve the accuracy and reproducibility of the
      analysis of anterior cervical fusion. An angular threshold of 2 degrees was
      selected for this purpose. This study showed that the rate of fusion with a
      dynamic plate was similar to that of the static plate despite the use of
      allograft bone with the dynamic plate. In addition, this study found that
      successful fusions continued to evolve throughout the first year following
      surgery.

PMID- 17545902
TI  - International collaboration beyond the culture gap.

PMID- 17545903
TI  - Foraminal stenosis and single-level degenerative disc disease: a randomized
      controlled trial comparing decompression with decompression and instrumented
      fusion.
AB  - STUDY DESIGN: A randomized controlled trial with 5-year outcome data. OBJECTIVE:
      To compare clinical outcomes following spinal decompression (Group 1) with those
      following decompression and instrumented posterolateral fusion (Group 2) and
      decompression and instrumented posterolateral fusion plus transforaminal
      interbody fusion (TLIF) (Group 3). SUMMARY OF BACKGROUND DATA: Decompression is
      frequently advocated for the relief of nerve root stenosis in the presence of
      degenerate disc disease. It is uncertain if spinal fusion is also necessary.
      MATERIALS AND METHODS: Following completion of a standardized physiotherapy
      program, 44 patients with single-level disc disease were randomly assigned to 1
      of 3 surgical groups. In those patients undergoing instrumentation, segmental
      pedicle screw fixation was used to stabilize the spine. Titanium interbody cages
      filled with autologous bone were inserted into patients in Group 3. Spinal
      disability, quality of life, and pain were assessed before surgery, and then at
      1, 2, and 5 years by an independent researcher. RESULTS: At 2 years, 82% of the
      patients were pain free or moderately improved. Disability (Low Back Outcome
      Score and Roland Morris index) were both better in Group 1, but only Low Back
      Outcome Score was better in Group 2 (P < 0.05). By 5 years, although patients in
      all 3 groups showed some improvements in all the ratings used (Low Back Outcome
      Score, SF-36 Physical Functioning, and Roland Morris score), only Group 1
      patients showed significant changes in all 3 outcomes (P < 0.05). There was no
      difference in any score between groups (P > 0.05). Two had secondary surgery for
      adjacent level stenosis (Group 2 and 3). One patient (Group 1) underwent
      subsequent lateral mass fusion for chronic pain. No patient required revision
      surgery for instrumentation failure, cage displacement, or pseudarthrosis.
      Evidence of at least unilateral lateral mass bone graft incorporation was evident
      in 95% of Groups 2 and 3. CONCLUSIONS: The results are encouraging in that almost
      all patients had improved by 5 years. However, it is a concern that no
      significant additional benefit has been noted from the more complex surgery. This
      suggests that patients are optimally treated by decompression alone, with the
      proviso that further operations may be required.

PMID- 17545904
TI  - Regulation of transgene expression using an inducible system for improved safety
      of intervertebral disc gene therapy.
AB  - STUDY DESIGN: Human nucleus pulposus cells (NPCs) were transduced with an
      adenoviral vector that expresses Fas Ligand (FasL) and green fluorescent protein
      (GFP) under the control of a tetracycline-regulated gene expression system to
      test the transgene control. OBJECTIVES: To describe the application of a Tet-off
      gene regulation system for intervertebral disc (IVD) gene therapy. SUMMARY OF
      BACKGROUND DATA: Gene therapy has proven its ability to beneficially modulate the
      biologic processes of the IVD cells in vitro and in vivo. However, we have
      observed that expression of transgenic growth factors outside the IVD in the
      event of a misdirected injection has potentially detrimental consequences (e.g.,
      toxicity). To date, a safety system that allows the control transgene expression
      has not been produced for intradiscal gene therapy. METHODS: Human NPCs were
      transduced with Ad/FasL-GFPTET, at 0, 50, 100, and 200 MOI. After 1 day (time 0)
      cells were cultured in the presence of tetracycline (1, 10, 100 mg/L) for 3 days,
      and then tetracycline was withdrawn. The transgene expression was evaluated
      either daily by flow cytometry (from time 0 to day 6) or by imaging the GFP
      signal (time 0, day 3 and day 9). RESULTS: NPC expression of GFP 1 day after
      transduction was proportional to the MOI used. GFP expression was decreased after
      3 days of tetracycline administration at all concentrations used. The expression
      of GFP recovered after removal of tetracycline. CONCLUSIONS: The transgene
      expressed by the transduced NPC was efficiently regulated by inclusion of
      tetracycline in culture media. The presence of tetracycline turns off the protein
      expression and the subsequent absence allows it to recover again, demonstrating
      the ability to control gene expression in NPCs. Therefore, we propose a Tet-off
      inducible system as an efficient tool for modulating the transgene expression to
      avoid the toxicity that could result from a missed injection.

PMID- 17545905
TI  - Safety of epidural administration of Osteogenic Protein-1 (OP-1/BMP-7):
      behavioral and macroscopic observation.
AB  - STUDY DESIGN: To assess the safety of epidural administration of Osteogenic
      Protein-1 (OP-1). OBJECTIVES: To examine if epidural administration of OP-1 or
      administration into the nucleus pulposus (NP) resulted in ectopic bone formation
      and/or pain-related behavior. SUMMARY OF BACKGROUND DATA: OP-1 has the potential
      for treatment of degenerative disc disease. However, OP-1's safety, when it is
      applied into the epidural space or herniated nucleus pulposus, is not well
      established. METHODS: Forty rats were divided into 5 groups. Sham group: Left L4
      and L5 nerve roots were exposed. NP group: The NP obtained from the tail was
      relocated onto the exposed nerve roots. NP+OP group: The NP obtained from the
      tail and injected with 0.2 microg of OP-1 in 1 microL of 5% lactose-buffered
      solution was placed on the nerve roots. GS group: A gelatin sponge was applied on
      the nerve roots. GS+OP group: A gelatin sponge soaked with 0.2 microg of OP-1 in
      1 microL of 5% lactose-buffered solution was placed onto the nerve roots. Motor
      function and reflex responses to mechanical noxious stimuli were measured in all
      rats up to 3 weeks after surgery. Three weeks after surgery, all rats were killed
      for analysis of ectopic bone formation and magnitude of neural compression.
      RESULTS: Motor paresis was not observed in any groups. Only rats in the NP group
      showed evidence of irreversible mechanical hyperalgesia after surgery. There were
      no differences in the mechanical stimuli response among all groups except the NP
      group. Macroscopic examination revealed no ectopic bone formation or differences
      in neural compression among the groups. CONCLUSION: OP-1 application in the
      epidural space is safe based on behavioral measures and macroscopic observation
      on ectopic bone formation at 21 days after surgery.

PMID- 17545906
TI  - In vivo measurements of lumbar segmental motion during axial rotation in
      asymptomatic and chronic low back pain male subjects.
AB  - STUDY DESIGN: Twenty male volunteers in their 30s (10 asymptomatic and 10 chronic
      low back pain) were passively rotated and CT scanned to determine lumbar
      segmental motion. OBJECTIVES: To determine the feasibility of measuring 3
      dimensional segmental motion in vivo in pain subjects. SUMMARY OF BACKGROUND
      DATA: Axial rotational spinal instability has been implicated as a potential
      cause of low back pain. Previous studies have not compared 3-dimensional
      segmental motions between healthy and symptomatic subjects due to torsion.
      METHODS: Lumbar segmental motions were calculated using volume merge method in 3
      major planes from 3-dimensional CT reconstructions. Disc degeneration grade was
      analyzed from MRI using the Thompson's grading method. RESULTS: All subjects
      could perform the imaging study without significant increase in pain. No
      differences were seen in disc degeneration grade or segmental motions between the
      2 groups. Segmental motion differences were seen in torsion, lateral bending, and
      frontal translation based on spinal level. CONCLUSIONS: Current noninvasive CT
      based method is feasible for use in healthy and low back pain subjects. Measured
      segmental motions were similar to other studies in torsion; however, other
      motions have not been measured previously.

PMID- 17545907
TI  - Biomechanical in vitro testing of human osteoporotic lumbar vertebrae following
      prophylactic kyphoplasty with different candidate materials.
AB  - STUDY DESIGN: Biomechanical study of human osteoporotic lumbar vertebrae
      following prophylactic kyphoplasty. OBJECTIVES: To evaluate the potential
      benefits of different resorbable candidate materials for use in prophylactic
      kyphoplasty compared with the behavior of polymethylmethacrylate cement. SUMMARY
      OF BACKGROUND DATA: Kyphoplasty using PMMA bone cement for the stabilization of
      fractured osteoporotic vertebrae has been established as a useful clinical tool.
      In several studies, consecutive compression fractures have been reported in
      vertebrae caudal or cranial to those augmented with bone cement. Consequently,
      some physicians have begun to treat adjacent vertebrae by means of prophylactic
      augmentation. METHODS: Biomechanical in vitro testing was performed on 40 human
      osteoporotic nonfractured lumbar vertebrae. Three types of bone cement (PMMA, 2
      different calcium phosphate cements) and one silicon derivative were assessed
      during compressive and cyclic sinusoidal testing. Each candidate material was
      applied bipedicularly under fluoroscopic control. RESULTS: Differing processing
      qualities of the materials led to substantial differences during cement
      injection, in particular in the amount of cement filling of the vertebrae.
      However, in comparison to native vertebrae, augmented specimens showed
      significantly higher compressive failure. No significant differences between
      vertebral bodies treated with PMMA and those treated with either type of calcium
      phosphate cement were documented. The biomechanical properties of the vertebrae
      could not be significantly improved by the silicon derivative. CONCLUSION: This
      study demonstrated that calcium phosphate cements displayed identical behavior to
      PMMA cement with respect to in vitro mechanical qualities. Consequently, from a
      mechanical viewpoint, calcium phosphate cements may be used in addition to PMMA
      cement for kyphoplasty and prophylactic kyphoplasty. Silicon derivatives are
      apparently not recommendable as candidate materials for kyphoplasty.

PMID- 17545908
TI  - The effects of anthropometrics, lifting strength, and physical activities in disc
      degeneration.
AB  - STUDY DESIGN: A cross-sectional study design was used. OBJECTIVE: The objective
      was to examine the influences of body anthropometrics, axial disc area, and
      lifting strength on disc degeneration and to compare these with the effects of
      lifetime physical demands and age. SUMMARY OF BACKGROUND DATA: Although recent
      studies have shown that heredity is a dominant factor in disc degeneration, the
      common notion that occupational physical loading is the major risk factor
      persists. However, substantial variations in disc degeneration, particularly at
      the lowest lumbar levels, remain unexplained by heredity or occupational physical
      demands. METHODS: Univariate methods and stepwise multiple regression modeling
      were used to estimate associations of body height, weight, fat content, axial
      disc area, isokinetic lifting performance, and lifetime routine physical
      activities at work and leisure with disc height narrowing and disc signal (in T2
      images) based on lumbar MRIs. These data were available from a population sample
      of 600 men, 35 to 70 years of age. RESULTS: Lower disc signal, representing disc
      desiccation, was associated with higher age, lower body mass and lifting
      strength, and larger axial disc area. Of the variance in disc signal, age
      explained 8.0% (P < 0.001) and body weight/axial disc area, isokinetic lifting
      strength, and occupational lifting history added 3.9%, 2.3%, and 1.3%,
      respectively. Greater disc narrowing was associated with higher age, larger axial
      disc area, and higher occupational physical loading. Of the variance in disc
      narrowing, age accounted for 3.8% (P < 0.001); axial disc area and occupational
      loading added 1.9% (P < 0.004) and 1.3% (P < 0.007), respectively. CONCLUSIONS:
      Body weight, lifting strength, and axial disc area were more highly associated
      with disc degeneration than occupational and leisure physical activity histories,
      although all had modest influences. Furthermore, higher body mass, greater
      lifting strength, and heavier work were all associated with more disc height
      narrowing but less disc desiccation contrary to current views. Smaller discs
      appeared to have beneficial effects.

PMID- 17545909
TI  - Outcome evaluation of surgical and nonsurgical management of lumbar disc
      protrusion causing radiculopathy.
AB  - STUDY DESIGN: Prospective cohort study. OBJECTIVE: To assess health-related
      quality of life (HRQOL) following either lumbar discectomy or nonoperative care
      for lumbar disc protrusion causing radiculopathy (LDPR). SUMMARY OF BACKGROUND
      DATA: Although LDPR is a prevalent disorder, little progress has been made in
      defining the optimal treatment strategy. METHODS: A total of 497 patients (333 in
      the lumbar discectomy group and 164 in the nonoperative group) were analyzed.
      Patients completed baseline as well as 6- and 12-month generic (SF-36) and
      disease-specific (NASS Lumbar Spine Instrument) HRQOL measures. Demographic
      comparisons between groups, using standard descriptive statistics, were made.
      Multivariate analysis was used to obtain a regression coefficient for the primary
      outcome: the neurogenic symptoms score (NSS) from the NASS instrument. Outcome
      measures were compared between groups and to published normative data. RESULTS:
      The mean baseline score was lower in the surgical group (30.9 nonoperative, 25.3
      surgical), indicative of greater baseline disability. The scores at follow-up
      were approximately equivalent (44.6 nonoperative, 43.8 surgical). However,
      neither group returned to an age-matched normative NSS (51.6) within the
      timeframe of the study. Using regression analysis, the outcome "change in NSS"
      was not associated with variable "treatment group." CONCLUSIONS: HRQOL after
      LDPR, as measured in this study by NASS NSS, demonstrated similar improvement in
      both groups and was not meaningfully associated with the treatment received,
      within the timeframe of this study. At follow-up, all outcome measures remained
      lower than population normative scores, suggesting that, irrespective of
      treatment, an element of disability remained.

PMID- 17545910
TI  - The relationship between the cross-sectional area of the cauda equina and the
      preoperative symptoms in central lumbar spinal stenosis.
AB  - STUDY DESIGN: A cross-sectional registry and imaging cohort study. OBJECTIVES: To
      study the association between typical symptoms and signs of central spinal
      stenosis and the minimum cross-sectional area (mCSA) of the cauda equina in
      patients subsequently undergoing surgery. SUMMARY OF BACKGROUND DATA: Relations
      between mCSA and the symptoms of spinal stenosis have not been studied before.
      SUBJECTS AND METHODS: The preoperative walking ability, pain in the leg(s) and
      back, duration of symptoms and quality of life in 82 men and women subsequently
      operated for spinal stenosis were related to the digitally determined CSA of the
      single most constricted level, mCSA of their lumbar spines. RESULTS: A smaller
      mCSA was directly related to a shorter walking distance before claudication. A
      small mCSA meant more leg and back pain and a lower health-related quality of
      life. For those with a walking ability <100 m, the average mCSA was around 53 mm;
      whereas it was just <69 mm for those able to walk >500 m. The average mCSA did
      not differ depending on gender, age, or vertebral level. CONCLUSIONS: The mCSA
      was a strong predictor of the preoperative walking ability, leg and back pain,
      and was directly related to the quality of life of patients with central spinal
      stenosis.

PMID- 17545912
TI  - Pelvic girdle pain and lumbar pain in relation to postpartum depressive symptoms.
AB  - STUDY DESIGN: A cohort study. OBJECTIVE: To investigate the possible association
      of lumbopelvic pain and postpartum depression and differences in the prevalence
      of depressive symptoms among women without lumbopelvic pain and women classified
      as having pelvic girdle pain (PGP) and/or lumbar pain. SUMMARY OF BACKGROUND
      DATA: Lumbopelvic pain and depression are common pregnancy complications, but
      their comorbidity has rarely been evaluated and has not been studied in relation
      to subgroups of lumbopelvic pain. METHODS: In a cohort of consecutively enrolled
      pregnant women, the Edinburgh Postnatal Depression Scale was used to evaluate
      depressive symptoms at 3 months postpartum, applying a primary screening cutoff
      of > or =10 and a cutoff of > or =13 for probable depression. Women were
      classified into lumbopelvic pain subgroups by means of mechanical assessment of
      the lumbar spine, standard history, pelvic pain provocation tests, a pain
      drawing, and the active straight leg raising test. RESULTS: The postpartum cohort
      (n = 267) comprised 180 (67%) women without lumbopelvic pain, 44 (16%) with PGP,
      29 (11%) with lumbar pain, and 14 (5%) with combined PGP and lumbar pain.
      Applying a cutoff of > or =10, postpartum depressive symptoms were more prevalent
      in women with lumbopelvic pain (27 of 87, 31%; 95% confidence interval, 26%-36%)
      than in women without lumbopelvic pain (17 of 180, 9%; 95% confidence interval,
      5%-13%; P < 0.001). The comorbidity of lumbopelvic pain and depressive symptoms
      was 10%. Depressive symptoms were more prevalent in women with lumbar pain versus
      women without lumbopelvic pain when applying cutoffs of > or =10 or > or =13 (P <
      or = 0.002); whereas for women with PGP, this comparison was significant only at
      the screening level of > or =10 (P = 0.01). CONCLUSIONS: Postpartum depressive
      symptoms were 3 times more prevalent in women having lumbopelvic pain than in
      those without. This comorbidity highlights the need to consider both symptoms in
      treatment strategies.

PMID- 17545913
TI  - Pelvic trauma with displaced sacral fractures: functional outcome at one year.
AB  - STUDY DESIGN: A prospective single-cohort study of 31 patients surgically treated
      for pelvic injuries with displaced sacral fractures. OBJECTIVE: To describe the
      medium term functional outcome in unstable sacral fractures. SUMMARY OF
      BACKGROUND DATA: Displaced sacral fractures pose a special challenge in
      orthopedic surgery due to the high rate of associated injuries. Little
      information is available on the medium-term functional outcome of patients with
      injuries which include unstable sacral fractures. METHODS: We examined 31
      patients with displaced sacral fractures having 10 mm or more displacement, 1
      year (mean, 1.4 years; range, 1.0-2.5 years) after injury. Data from a previous
      study were supplemented with functional outcome measures (work status,
      independence in ADL, and SF-36). An association between outcome and tested
      variables was sought. RESULTS: Fifteen months after injury, 65% of the patients
      had regained their independence in functions pertaining to daily activities; 33%
      had returned to work. All dimensions of perceived health were affected.
      Polytrauma and impairments relative to voiding and sexual function had a
      detrimental effect on outcome. Fracture characteristics were not predictive of
      poor outcome. CONCLUSIONS: Although the majority of patients achieved independent
      living, medium-term follow-up indicated significant residual disability. The
      complex nature of these fractures and the associated injuries should be
      considered in the rehabilitation of these patients.

PMID- 17545914
TI  - Variation in care among spinal deformity surgeons: results of a survey of the
      Shriners hospitals for children.
AB  - STUDY DESIGN: Survey. OBJECTIVE: To understand the variation in scoliosis surgery
      and perioperative care among spinal deformity surgeons. SUMMARY OF BACKGROUND
      DATA: While variation in care has been well described in many spinal disorders,
      the degree of variation has not been described for spinal deformity. METHODS:
      Clinical histories and radiographs of 4 typical spinal deformity patients were
      sent to spinal deformity surgeons for review. The cases consisted of idiopathic
      thoracolumbar, double major, and right thoracic curves and a neuromuscular lumbar
      curve. The survey queried choice of surgical approach, levels fused and
      instrumented, type of instrumentation, preoperative testing, intraoperative
      neurologic monitoring, blood and antibiotic use, and postoperative care,
      including pain control and patient mobilization. Cost estimates for each case
      were obtained from the individual hospitals' pricing. RESULTS: There was wide
      variation in the specific fusion levels and instrumentation for the idiopathic
      curves. The variation was greatest for the thoracolumbar curve. The double major
      and right thoracic curves differed primarily in their choice of instrumenting
      secondary curves. The neuromuscular curve had the least variation. Costs
      estimates were widely disparate between centers. Perioperative care had much less
      disparity. CONCLUSIONS: Agreement appears common in areas with readily
      identifiable outcomes such as shorter length of stay and rapid postoperative
      mobilization. However, agreement is poor in areas where outcomes are difficult to
      measure and require long-term follow-up such as instrumentation fusion and
      levels.

PMID- 17545915
TI  - Imaging assessment of lumbar pedicle screw placement: sensitivity and specificity
      of plain radiographs and computer axial tomography.
AB  - STUDY DESIGN: This is a diagnostic study in which cadavers were evaluated by
      imaging and dissection after pedicle screw placement. OBJECTIVE: This study was
      designed to evaluate the accuracy of plain radiographs and/or CT in determining
      pedicle instrumentation. SUMMARY OF BACKGROUND DATA: One biomechanical advantage
      provided by pedicle screws fixation is improved fusion rates. The accuracy of
      pedicle screw placement has relied on radiograph and CT. Our goal is to evaluate
      the accuracy of these methods. METHODS: Cadaveric lumbar spines were exposed by a
      posterior approach. Titanium pedicle screws were inserted. Radiographs and CTs
      were obtained. The spines were then dissected to examine screw location. A
      blinded examiner reviewed the imaging. Screws were considered misaligned if they
      were extrapedicular or had evidence of cortical perforation. RESULTS: The
      sensitivity of radiographs, CT, and combined is 93.9%, 94%, and 98.7%,
      respectively. The specificity of radiograph, CT, and combined is 12.5%, 36.7%,
      and 40.7%, respectively. The positive predictive value for radiograph, CT, and
      combined is 83.2%, 88.1%, and 90.4%, respectively. The negative predictive value
      for radiograph, CT, and combined is 30.8%, 55.9%, and 84.6%, respectively. The
      accuracy of radiograph, CT, and combined is equal to 79.4%, 84.4%, and 90%,
      respectively. CONCLUSION: Patients who present with significant complaints of
      pain or neurologic deficits, optimal determination of pedicle screw positions is
      with the combination of radiographs and CT. Furthermore, routine evaluation of
      patients' status post pedicle screw fixation can be reliable obtained with
      radiographs. The biomechanical advantage of pedicle screw fixation has improved
      fusion rates and diminished the number of levels required for stability. Despite
      the widespread clinical use of pedicle screw fixation, there is relatively little
      literature concerning accuracy. This study was designed to evaluate the accuracy
      of plain radiographs and/or CT in determining the proper position of pedicle
      screws.

PMID- 17545916
TI  - Back muscle response to sudden trunk loading can be modified by training among
      healthcare workers.
AB  - STUDY DESIGN: Experimental study of the effect of physical training on the
      reaction to sudden back loading. OBJECTIVE: To investigate the effect and
      sustainability of "on the job training" on the reaction to sudden back loading
      among employees at a geriatric ward. SUMMARY OF BACKGROUND DATA: Available data
      suggest that a delayed muscle reflex response to sudden trunk loading may
      increase the risk of low back injuries. We have previously shown that training
      may alter the response to sudden trunk loading in healthy subjects and decrease
      the time elapsed until stopping of the forward movement of the trunk (stopping
      time). Data on the possibilities of a training-induced improvement in the reflex
      response among workers exposed to sudden trunk loading on the job are, however,
      nonexistent, and there is no evidence of long-term benefits, i.e., the
      sustainability of a positive training effect. METHODS: The study included 23
      participants and 14 controls. All were healthy without prior history of low back
      pain (LBP). The training group participated in a total of 18 training sessions
      during a 9-week period. The training focused on reactions to a variety of sudden
      trunk loadings. Before and after the training intervention and at a 1-year follow
      up, all subjects were tested for their reaction to expected and unexpected sudden
      trunk loading by applying a horizontal force of 58 N to the upper back of the
      subjects and measuring the electromyographic (EMG) response from the erector
      spinae muscles. RESULTS: In the training group, the stopping time and the
      distance moved after unexpected sudden trunk loading decreased significantly (13%
      19%, P = 0.02). The improved stopping time was associated with marked changes in
      the time-wise distribution of the EMG signal after training. In addition, the
      follow-up study showed a high sustainability of the training effect. CONCLUSIONS:
      The results demonstrated a training-induced improvement of the response to sudden
      trunk loading that may be beneficial in workers, such as nurses, who are exposed
      to sudden trunk perturbations during patient handling.

PMID- 17545917
TI  - Translation, adaptation, and validation of the Moroccan version of the Roland
      Morris Disability Questionnaire.
AB  - STUDY DESIGN: Cross-cultural adaptation and cross-sectional psychometric testing.
      OBJECTIVES: To translate and culturally adapt the Moroccan version of the Roland
      Morris Disability Questionnaire and to validate its use for assessing disability
      in Moroccan patients with low back pain (LBP). SUMMARY OF BACKGROUND DATA: The
      RMDQ is a reliable evaluation instrument for LBP disability, but no validated
      Moroccan version is available. METHODS: The RMDQ was translated and back
      translated to dialectal Arabic, pretested, and reviewed by a committee following
      the Guillemin criteria. It was then validated on 76 Moroccan patients with
      chronic LBP. Reliability for the 1-week test-retest was assessed using internal
      consistency by Cronbach's alpha coefficient, the intraclass correlation
      coefficient, and the constructed Bland Altman plot. Structure validity was
      evaluated by multiple correspondence analysis. External construct validity was
      assessed by association with pain, spinal mobility, and other key variables
      (weight, height, duration of LBP). RESULTS: The reproducibility of the 24 items
      was satisfactory with a kappa statistic of agreement superior to 0.6 except item
      10 and ranging from 0.47 to 0.9. The intraclass correlation coefficient for
      global score reproducibility was good and reached 0.93 (95% confidence interval,
      0.89-0.95). The constructed Bland and Altman plot for test-retest agreement
      showed a good reliability. The internal consistency was very good with a
      Cronbach's alpha coefficient of 0.96. The multiple correspondence analysis for
      internal structure validity showed a preponderant factor explaining 22% of the
      variance in the score. The construct validity showed a positive correlation
      between RMDQ and the visual analog scale (r = 0.32; P = 0.005). There was no
      statistic correlation between RMDQ and the other variables. CONCLUSION: The
      Moroccan version of the RMDQ has good comprehensibility internal consistency,
      reliability, and validity for the evaluation of Moroccan-speaking patients with
      LBP.

PMID- 17545919
TI  - The impact of extroversion or menopause status on depressive symptoms among
      climacteric women in Taiwan: neuroticism as moderator or mediator?
AB  - OBJECTIVE: The study was designed to test whether neuroticism moderated the
      effect of extroversion and mediated the impact of menopause status on depressive
      symptoms among women in Taiwan during their menopausal transition. DESIGN: A
      sample of 197 women, aged 40 to 60 years, were recruited from the community. We
      used Ko's Depression Inventory, the Five-Factor Inventory-Chinese version, the
      Menopausal Symptoms Scale, and the Chinese version of the Modified Schedule of
      Affective Disorders and Schizophrenia-Lifetime to gather data. Moreover, each
      woman underwent a semistructured diagnostic interview in person to obtain her
      lifetime psychiatric history. RESULTS: The hierarchy regression analyses showed
      that the interaction between neuroticism and extroversion was statistically
      significant. Further analyses indicated that in the high neuroticism group,
      extroversion was negatively associated with depressive symptoms; however, in the
      low neuroticism group, extroversion was not correlated with depressive symptoms.
      Menopause status was correlated with depressive symptoms, but after adding
      neuroticism and extroversion, the main effect of menopause status became
      insignificant. Results of the Sobel test showed that depressive symptoms of women
      during the menopause transition largely represented neuroticism. CONCLUSIONS: The
      present study revealed that the lower levels of extroversion are associated with
      depression among all stages of menopausal women with high levels of neuroticism;
      moreover, all stages of menopausal women who have high levels of neuroticism are
      more vulnerable to depression. The results support that personality may play an
      important role in women's depression during the transition of menopausal status.

PMID- 17545920
TI  - Lignan-rich sesame seed negates the tumor-inhibitory effect of tamoxifen but
      maintains bone health in a postmenopausal athymic mouse model with estrogen
      responsive breast tumors.
AB  - OBJECTIVE: Flaxseed, the richest source of mammalian lignan precursors, enhances
      the tumor growth-inhibitory effect of tamoxifen while exerting no adverse effects
      on other estrogen-responsive tissues such as bone. Ingestion of sesame seed
      produces mammalian lignans comparable with flaxseed, but its anticancer potential
      is unknown. This study determined the interactive effects of sesame seed and
      tamoxifen on established MCF-7 tumor growth and bone health in ovariectomized
      athymic mice simulating a postmenopausal condition. DESIGN: Mice with established
      MCF-7 tumors were treated for 8 weeks with (1) basal diet (negative control), (2)
      10% sesame seed, (3) basal diet + tamoxifen implant, (4) 10% sesame seed +
      tamoxifen implant, or (5) basal diet + estrogen implant (positive control).
      Weekly palpable tumor size, final tumor weight, cell proliferation, and apoptosis
      were measured. Bone mineral content, bone mineral density, and biomechanical
      strength testing were performed on the femur and lumbar vertebrae. RESULTS:
      Sesame seed induced regression of established tumor size similar to the negative
      control but tended to negate the tumor-inhibitory effect of tamoxifen, in part by
      reducing apoptosis. Sesame seed combined with tamoxifen induced higher bone
      mineral content, bone mineral density, and biomechanical strength in the femur
      and lumbar vertebrae than either treatment alone. A significant positive
      relationship was found between final tumor weight and bone strength parameters.
      CONCLUSIONS: Sesame seed is not protective and negatively interferes with
      tamoxifen in inducing regression of established MCF-7 tumor size but beneficially
      interacts with tamoxifen on bone in ovariectomized athymic mice.

PMID- 17545921
TI  - Circulating osteoprotegerin is associated with age and systolic blood pressure,
      but not with lipid profile or fasting glucose, in postmenopausal women.
AB  - OBJECTIVE: Osteoprotegerin (OPG), an inhibitor of osteoclastogenesis and
      osteoclast activation, has been reported to be linked to vascular biology. The
      aim of this study was to clarify the relationships between circulating OPG and
      the risk factors for vascular disorders in postmenopausal women. DESIGN: Eighty
      Japanese postmenopausal women were enrolled in this cross-sectional study.
      Clinical parameters (age, number of years since menopause, body mass index,
      systolic and diastolic blood pressure); serum concentrations of OPG, creatinine,
      calcium, and phosphorus; serum lipid profile; plasma glucose; and bone mineral
      density of the L2-4 vertebral bodies were determined for each woman. RESULTS: In
      rank-order correlation analysis, serum OPG concentrations had significant
      positive correlations with age (r = 0.29, P = 0.03), systolic blood pressure (r =
      0.45, P < 0.01), diastolic blood pressure (r = 0.34, P < 0.01), and serum
      creatinine (r = 0.29, P = 0.04). Serum OPG concentration also had a marginally
      significant negative correlation with bone mineral density of the L2-4 vertebral
      bodies (r = -0.25, P = 0.06). However, serum OPG did not correlate with body mass
      index, serum lipid profile, or plasma glucose. The correlation of serum OPG with
      systolic blood pressure persisted after adjustment for both age and serum
      creatinine. CONCLUSIONS: These results suggest that increased circulating OPG in
      postmenopausal women is closely related to higher systolic blood pressure, which
      could cause atherosclerosis.

PMID- 17545923
TI  - To the editor. Post menopausal hormone therapy in clinical perspective.

PMID- 17545925
TI  - The use of repeated head computed tomography in pediatric blunt head trauma:
      factors predicting new and worsening brain injury.
AB  - OBJECTIVE: Opinion is divided on the value of repeat head computed tomography for
      guiding clinical management of pediatric patients with blunt head trauma. This
      study describes the prevalence of worsening brain injury on repeat computed
      tomography, predictors of worsening computed tomography findings, and the
      frequency of neurosurgical intervention after the repeat computed tomography.
      DESIGN: Retrospective cohort study. SETTING: All patients were admitted to a
      level I pediatric trauma center between 1994 and 2003. PATIENTS: Children <15 yrs
      old with two or more head computed tomographies following hospital admission for
      blunt head trauma. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We
      reviewed the imaging reports to determine injury progression. Potential
      predictors of worsening computed tomography findings and neurosurgical
      intervention were recorded by chart review. Logistic regression and recursive
      partitioning were used to identify predictors. Twenty percent (50 of 257) of
      patients with mild head injury had worsening computed tomography findings, and
      three patients (1%) had subsequent neurosurgical intervention. Patients with
      moderate and severe head injuries were more likely to have worsening computed
      tomography findings (107 of 248; 43%) and to have neurosurgical intervention (15
      of 248; 6%). In most surgical patients, repeat computed tomography was preceded
      by rapid decline in neurologic status or elevated intracranial pressure.
      Stratification based on four clinical factors (initial head injury severity, any
      intraparenchymal finding on initial computed tomography, normal findings on
      initial computed tomography, coagulopathy) identified 100% of the surgical
      patients and 89% of patients with worsening brain injuries on the repeat computed
      tomography. CONCLUSIONS: Repeat head computed tomography imaging is frequently
      used. About 30% of repeated computed tomographies showed new or worsening brain
      injury. However, worsening brain injury on repeat computed tomography rarely
      resulted in neurosurgical intervention. Patients with moderate or severe head
      injury and intraparenchymal injuries were more likely to show worsening brain
      injury and undergo neurosurgical intervention.

PMID- 17545926
TI  - Going back for more: an evaluation of clinical outcomes and characteristics of
      readmissions to a pediatric intensive care unit.
AB  - OBJECTIVE: To determine mortality, length of stay, and factors associated with
      readmissions to the pediatric intensive care unit (PICU). DESIGN: A retrospective
      analysis of prospectively collected data. SETTING: A 16-bed medical-surgical
      tertiary PICU and a coexisting 15-bed pediatric cardiac intensive care unit.
      PATIENTS: All admissions from July 1, 1998, through June 30, 2004. INTERVENTIONS:
      None. MEASUREMENTS AND RESULTS: Of 8,885 total eligible admissions, 711 (8%) were
      readmissions to the PICU. The median age of the overall cohort was 35.2 months
      (interquartile range, 5.5-128.2). Readmitted patients were younger (10.4 vs. 37.7
      months, p < .01), had greater severity of illness (p < .01), and were more likely
      to be admitted emergently (p < .01), in comparison with single admissions. In
      multivariate analyses, readmitted patients had a trend toward higher odds of
      mortality (odds ratio, 1.39; 95% confidence interval, 0.98-1.98) and stayed 2.96
      days longer in the PICU (95% confidence interval, 1.98-3.94) compared with single
      admissions to the PICU. Factors independently associated with PICU readmission
      were infant age (odds ratio, 1.98; 95% confidence interval, 1.57-2.49), emergent
      admission (odds ratio, 2.21; 95% confidence interval, 1.78-2.77), illness
      severity (odds ratio, 1.03; 95% confidence interval, 1.01-1.04), and time of the
      year between July and September (odds ratio, 1.52; 95% confidence interval, 1.20
      1.93). A diagnosis of trauma was associated with low likelihood of PICU
      readmission (odds ratio, 0.30; 95% confidence interval, 0.18-0.50). CONCLUSIONS:
      Patients readmitted to the PICU during the same hospitalization have
      significantly adverse outcomes. The study highlights important factors associated
      with PICU readmissions that can be incorporated into efforts to reduce mortality
      and resource utilization associated with readmission of critically ill children.

PMID- 17545927
TI  - Association of nursing workload and unplanned extubations in a pediatric
      intensive care unit.
AB  - OBJECTIVE: To estimate nursing workload from the patient acuity level (PAL)
      assigned to patients in a pediatric intensive care unit (PICU) and to determine
      its influence on unplanned extubations. DESIGN: Prospective cohort study.
      SETTING: The 19-bed PICU of an urban, university-affiliated, tertiary children's
      hospital. PATIENTS: All patients admitted to the PICU. INTERVENTIONS: None.
      MEASUREMENTS AND MAIN RESULTS: The study encompassed 2,193 nursing shifts and
      1,919 admissions to the PICU over 24 months. The shift census averaged 12.0
      patients (range 5-18) and was staffed by 9.4 nurses (range 4-16) for an average
      patient/nurse ratio of 1.3 +/- 0.2. Patients were assigned a PAL of 1-7 based on
      a classification system derived from time studies of 12 general nursing tasks.
      The total PALs per shift divided by the number of nursing staff yielded an
      average assignment of 5.8 +/- 0.7 PALs. Forty unplanned extubations (0.76
      unplanned extubations/100 ventilator days) were observed during the study period.
      Logistic regression revealed positive associations between unplanned extubations
      and patient/nurse ratio (p = .03) and the shift PAL/nurse ratio (p = .01). The
      likelihood of an unplanned extubation when nurses covered >6.3 PALs was 3.8 times
      higher than during those shifts when they covered <5.3 PALs. CONCLUSIONS: The
      likelihood of an unplanned extubation increased with higher patient/nurse and
      patient acuity/nurse ratios. Successful interventions to reduce the frequency of
      this medical error may need to address both nurse demand methodology and
      workload.

PMID- 17545928
TI  - Continuous venovenous hemofiltration with or without extracorporeal membrane
      oxygenation in children.
AB  - OBJECTIVES: We report the frequency of usage, patient demographics, and outcomes
      in children treated with continuous venovenous hemofiltration (CVVH) in three
      pediatric intensive care units (PICUs), with one unit providing combined
      extracorporeal membrane oxygenation (ECMO) and CVVH. DESIGN: Prospective database
      analysis. SETTING: Three regional PICUs in the Trent Haemofiltration Network with
      two general PICUs admitting 450-500 patients annually and the other providing
      regional cardiac support and a supraregional service for ECMO (600-650 admissions
      annually with 50 ECMO patients). PATIENTS: Children who underwent CVVH alone or
      in combination with ECMO or other therapies between January 2000 and December
      2002. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: There were 115 children
      (58 male) treated, with a median age of 18 months (range 1 day to 17 yrs) and
      median weight of 12 kg (range 1.8-119 kg). In the two PICUs without ECMO, CVVH
      was undertaken in 2.5% of admissions annually compared with 3% of annual
      admissions to the PICU with an ECMO service. Fifty-five patients received CVVH
      alone (group 1), while 53 patients underwent CVVH in conjunction with ECMO (group
      2). In addition, five patients received plasmafiltration followed by CVVH, and
      two patients were treated with combined CVVH and molecular adsorbents
      recirculating system. Mean duration of therapy in group 1 was 142 hrs (1-840 hrs)
      and in group 2,231 hrs (3-1104 hrs). Overall patient survival was 43% with 29 of
      55 (53%) CVVH patients surviving and 18 of 53 (34%) of those treated with ECMO
      plus CVVH. CONCLUSIONS: Performing CVVH in a heterogeneous population with large
      age and weight ranges poses significant clinical and technical challenges. The
      low frequency of CVVH use, as well as the use of other extracorporeal therapies,
      also raises problems with maintaining nursing skills. Objective clinical and
      biochemical markers for commencing CVVH alone or in combination with ECMO remain
      to be defined.

PMID- 17545929
TI  - Fatal acute fibrinous and organizing pneumonia in an infant: The histopathologic
      variability of acute respiratory distress syndrome.
AB  - OBJECTIVE: The histopathologic pattern of acute fibrinous and organizing
      pneumonia (AFOP) has been described recently in cases of acute respiratory
      distress syndrome (ARDS) in adults and differs from the well-recognized pattern
      of classic diffuse alveolar damage (DAD). The objective of this study was to
      determine whether similar appearances can be seen in infant ARDS. DESIGN: Case
      report and retrospective review of infant lung biopsies 1995-2005. SETTING:
      Paediatric and neonatal intensive care units in a tertiary referral center.
      PATIENTS: None. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A formerly
      premature infant with ARDS secondary to respiratory syncytial virus pneumonitis
      had histopathologic features of AFOP on open lung biopsy. Nine infants from 1995
      to 2005 had definite histology of DAD or AFOP and fulfilled American-European
      Consensus Conference criteria for the diagnosis of ARDS. Of these, classic DAD
      findings were present in seven, whereas two had features of AFOP and DAD.
      Features suggesting viral infection were identified in five infants. CONCLUSIONS:
      The histopathologic features of AFOP may be seen in some cases of infant ARDS.
      The variability in the histopathology of ARDS raises questions as to the
      pathogenesis and clinical correlates of these different patterns.

PMID- 17545930
TI  - Parental involvement in treatment decisions regarding their critically ill child:
      a comparative study of France and Quebec.
AB  - OBJECTIVE: To examine whether physicians or parents assume responsibility for
      treatment decisions for critically ill children and how this relates to
      subsequent parental experience. A significant controversy has emerged regarding
      the role of parents, relative to physicians, in relation to treatment decisions
      for critically ill children. Anglo-American settings have adopted decision-making
      models where parents are regarded as responsible for such life-support decisions,
      while in France physicians are commonly considered the decision makers. DESIGN:
      Grounded theory qualitative methodology. SETTING: Four pediatric intensive care
      units (two in France and two in Quebec, Canada). PATIENTS: Thirty-one parents of
      critically ill children; nine physicians and 13 nurses who cared for their
      children. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Semistructured
      interviews were conducted. In France, physicians were predominantly the decision
      makers for treatment decisions. In Quebec, decisional authority practices were
      more varied; parents were the most common decision maker, but sometimes it was
      physicians, while for some decisional responsibility depended on the type of
      decision to be made. French parents appeared more satisfied with their
      communication and relationship experiences than Quebec parents. French parents
      referred primarily to the importance of the quality of communication rather than
      decisional authority. There was no relationship between parents' actual
      responsibility for decisions and their subsequent guilt experience. CONCLUSIONS:
      It was remarkable that a certain degree of medical paternalism was unavoidable,
      regardless of the legal and ethical norms that were in place. This may not
      necessarily harm parents' moral experiences. Further research is required to
      examine parental decisional experience in other pediatric settings.

PMID- 17545931
TI  - Acute lung injury in pediatric intensive care in Australia and New Zealand: a
      prospective, multicenter, observational study.
AB  - OBJECTIVE: Acute lung injury (ALI) is poorly defined in children. The objective
      of this prospective study was to clarify the incidence, demographics, management
      strategies, outcome, and mortality predictors of ALI in children in Australia and
      New Zealand. DESIGN: Multicenter prospective study during a 12-month period.
      SETTING: Intensive care unit. PATIENTS: All children admitted to intensive care
      and requiring mechanical ventilation were screened daily for development of ALI
      based on American-European Consensus Conference guidelines. Identified patients
      were followed for 28 days or until death or discharge. INTERVENTIONS: None.
      MEASUREMENTS AND MAIN RESULTS: There were 117 cases of ALI during the study
      period, giving a population incidence of 2.95/100,000 <16 yrs. ALI accounted for
      2.2% of pediatric intensive care unit admissions. Mortality was 35% for ALI, and
      this accounted for 30% of all pediatric intensive care unit deaths during the
      study period. Significant preadmission risk factors for mortality were chronic
      disease, older age, and immunosuppression. Predictors of mortality during
      admission were ventilatory requirements (peak inspiratory pressures, mean airway
      pressure, positive end-expiratory pressure) and indexes of respiratory severity
      on day 1 (Pao2/Fio2 ratio and oxygenation index). Higher maximum and median tidal
      volumes were associated with reduced mortality, even when corrected for severity
      of lung disease. Development of single and multiple organ failure was
      significantly associated with mortality. CONCLUSIONS: ALI in children is uncommon
      but has a high mortality rate. Risk factors for mortality are easily identified.
      Ventilatory variables and indexes of lung severity were significantly associated
      with mortality.

PMID- 17545932
TI  - Prevalence of heparin-dependent platelet antibodies in children after
      cardiopulmonary bypass.
AB  - OBJECTIVE: To determine the prevalence of heparin-dependent platelet antibodies
      (HDPA) in children requiring heparin for >5 days after cardiopulmonary bypass
      surgery. DESIGN: Prospective, observational study. SETTING: Tertiary care
      pediatric intensive care unit. PATIENTS: Thirty children were enrolled: 15
      patients <30 days old and 15 patients between 30 days and 12 yrs of age.
      INTERVENTIONS: Detection of HDPA by heparin-platelet factor 4 enzyme-linked
      immunosorbent assay after 5-10 days of postoperative heparin exposure. Positive
      or equivocal results were confirmed with serotonin release assay. MEASUREMENTS
      AND MAIN RESULTS: There were no confirmed cases of HDPA in this study (95%
      confidence interval 0-11.6%). Despite the lack of HDPA, the study population was
      at high risk of thrombosis with symptomatic clot developing in six patients
      (20%). Clinical models developed in adults to determine the pretest risk of
      heparin-induced thrombocytopenia were not valid in this study population.
      CONCLUSIONS: The prevalence of HDPA in children after cardiopulmonary bypass
      surgery is low. After bypass surgery, critically ill children are at risk of
      developing thrombosis from multiple etiologies, and suspicion of heparin-induced
      thrombocytopenia needs to be confirmed with laboratory testing including a
      functional assay.

PMID- 17545933
TI  - Invasive nosocomial aspergillosis associated with heart failure and complete
      heart block following recovery from dengue shock syndrome.
AB  - OBJECTIVE: To report a case of invasive aspergillosis, associated with complete
      heart block and heart failure, in an immunocompetent child recovering from dengue
      shock syndrome. DESIGN: Case report and literature review. SETTING: Pediatric
      intensive care unit in a tertiary care center. PATIENT AND RESULTS: A 9-yr-old
      boy was admitted to our pediatric intensive care unit with dengue shock syndrome,
      for which he was successfully managed. During the recovery phase, the child
      developed recurrence of fever and signs of congestive heart failure. Thereafter,
      he developed complete heart block and died. Myocardial biopsy revealed
      myocarditis and invading fungal elements with branching septate hyphae suggestive
      of Aspergillus. A renal biopsy specimen also showed glomerular invasion with
      Aspergillus and patchy necrosis. This suggested the diagnosis of invasive
      aspergillosis. CONCLUSIONS: This case highlights an unusual manifestation of
      invasive aspergillosis in a critically ill immunocompetent child.

PMID- 17545934
TI  - Co-ingestion of methanol and nitromethane: using falsely elevated creatinine as
      indicator for methanol antidote use.
AB  - OBJECTIVE: To report a case of co-ingestion of methanol and nitromethane in a
      child in order to heighten the awareness of false elevation of serum creatinine
      from nitromethane ingestion. DESIGN: Case report. SETTING: Pediatric intensive
      care unit. PATIENT: A 4-yr-old previously healthy girl ingested an unknown
      quantity of "Blue Thunder" model-engine fuel, which consisted of methanol and
      nitromethane. The patient was treated with fomepizole for methanol ingestion
      using elevated creatinine level as a reason for treatment. RESULTS: The patient
      was asymptomatic but her creatinine level increased ten-fold (from 0.4 mg/dL to 4
      mg/dL) within 6 hrs. Blood urea nitrogen, anion gap, and osmolar gap remained
      within normal limits. When the serum creatinine level was measured with enzymatic
      method instead of Jaffe's method, a normal creatinine level was obtained. The
      falsely elevated creatinine level was due to nitromethane. CONCLUSION: The
      falsely elevated serum creatinine levels due to nitromethane ingestion can lead
      to unnecessary therapeutic interventions. We intend to heighten awareness of this
      potential misstep by reporting this case.

PMID- 17545935
TI  - Chylothorax and child abuse.
AB  - OBJECTIVE: Report of an unusual presentation of child abuse in a critical care
      setting. DESIGN: Case report. SETTING: Pediatric intensive care unit of a
      tertiary care hospital. PATIENT: A 6-month-old infant. BACKGROUND: Chylothorax in
      young children can be a sign of systemic illness or a nondisease entity
      (idiopathic); however, it also can be the only apparent manifestation of child
      abuse. CLINICAL RELEVANCE: Child abuse can present with unusual findings, and the
      diagnosis is not always apparent. In this and previous case reports of child
      abuse presenting as chylothorax, the diagnosis of abusive injury was not
      initially made by the managing clinicians. When abusive injury is in the
      differential diagnosis of a child's condition, a thorough and complete
      investigation-including skeletal survey, eye exam by an ophthalmologist, cranial
      neuroimaging, and consultation with child abuse physicians and child protective
      services-may be indicated. CONCLUSION: Before diagnosis of idiopathic chylothorax
      is made in a young child, clinicians should reexamine the patient and all
      radiographic studies, searching for findings that may indicate abuse. Further
      evaluation with a dedicated skeletal survey is suggested.

PMID- 17545937
TI  - Have changes in ventilation practice improved outcome in children with acute lung
      injury?
AB  - OBJECTIVES: To describe the changes that have occurred in mechanical ventilation
      in children with acute lung injury in our institution over the last 10-15 yrs and
      to examine the impact of these changes, in particular of the delivered tidal
      volume on mortality. DESIGN: Retrospective study. SETTING: University-affiliated
      children's hospital. PATIENTS: The management of mechanical ventilation between
      1988 and 1992 (past group, n = 79) was compared with the management between 2000
      and 2004 (recent group, n = 85). INTERVENTIONS: None. MEASUREMENTS AND MAIN
      RESULTS: The past group patients were ventilated with a significantly higher mean
      tidal volume (10.2 +/- 1.7 vs. 8.1 +/- 1.4 mL.kg actual body weight, p < .001),
      lower levels of positive end-expiratory pressure (6.1 +/- 2.7 vs. 7.1 +/- 2.4 cm
      H2O, p = .007), and higher mean peak inspiratory pressure (31.5 +/- 7.3 vs. 27.8
      +/- 4.2 cm H2O, p < .001) than the recent group patients. The recent group had a
      lower mortality (21% vs. 35%, p = .04) and a greater number of ventilator-free
      days (16.0 +/- 9.0 vs. 12.6 +/- 9.9 days, p = .03) than the past group. A higher
      tidal volume was independently associated with increased mortality (odds ratio
      1.59; 95% confidence interval 1.20, 2.10, p < .001) and reduction in ventilation
      free days (95% confidence interval -1.24, -0.77, p < .001). CONCLUSIONS: The
      changes in the clinical practice of mechanical ventilation in children in our
      institution reflect those reported for adults. In our experience, mortality among
      children with acute lung injury was reduced by 40%, and tidal volume was
      independently associated with reduced mortality and an increase in ventilation
      free days.

PMID- 17545938
TI  - Relationship between physiologic deadspace/tidal volume ratio and gas exchange in
      infants with acute bronchiolitis on invasive mechanical ventilation.
AB  - OBJECTIVES: To evaluate the association between deadspace/tidal volume ratio
      (Vd/Vt) and gas exchange variables: Pao2, Paco2, Pao2/Fio2, arterial/alveolar
      oxygen tension ratio (Pao2/PAo2), alveolar-arterial oxygen tension
      difference/arterial oxygen tension ratio (P(A-a)o2/Pao2), carbon dioxide
      production (Vco2), ventilation index ([Paco2 x peak inspiratory pressure x
      mechanical respiratory rate]/1000), and oxygenation index ([mean airway pressure
      x Fio2 x 100]/Pao2), all measured at an early stage in children with obstructive
      acute respiratory failure. DESIGN: Prospective, cross-sectional, observational
      study. SETTING: Pediatric intensive care unit, university hospital. PATIENTS:
      Twenty-nine infants with acute bronchiolitis, defined according to clinical and
      radiologic criteria. Children with chronic pulmonary disease, neuromuscular
      disease, congenital cardiopathies, or hemodynamic instability were excluded.
      INTERVENTIONS: Measurements were made between 24 and 72 hrs of mechanical
      ventilation using volumetric capnography and arterial blood gas analysis.
      MEASUREMENTS AND MAIN RESULTS: The following variables significantly correlated
      with Vd/Vt, calculated using Spearman's correlation coefficient (rs): Pao2 (rs = 
      0.63, p < .001), Pao2/Fio2 (rs = -0.56, p = .002), Pao2/PAo2 (rs = -0.46, p =
      .012), P(A-a)o2/Pao2 (rs = -0.46, p = .012), Paco2 (rs = 0.51, p = .005), Vco2
      (rs = -0,62, p < .01), oxygenation index (rs = 0.48, p = .009), and ventilation
      index (rs = -0.53, p = .003). A statistically significant association was found
      between an increase in Vd/Vt and severity of lung injury, defined as Pao2/Fio2
      <200 (p = .03, Mann-Whitney). CONCLUSIONS: In the study population, Vd/Vt not
      only reflected ventilatory disorders, as is well recognized, but also was
      associated with disturbances of oxygenation. These results warrant further
      evaluation of the usefulness of serial measurement of Vd/Vt as a marker of
      disease severity in severe acute bronchiolitis and other causes of respiratory
      failure.

PMID- 17545939
TI  - Glucosamine administration improves survival rate after severe hemorrhagic shock
      combined with trauma in rats.
AB  - We have previously shown that glucosamine administration resulted in higher
      cardiac output and improved tissue perfusion after trauma-hemorrhage with
      resuscitation in rats, which was associated with the increased levels of protein
      O-linked-N-acetylglucosamine (O-GlcNAc). The purpose of the study was to evaluate
      the effect of glucosamine on the survival, without resuscitation, in rats. Adult
      male rats underwent midline laparotomy and 55% of total blood volume was
      withdrawn for 25 min under isoflurane anesthesia. At the end of the hemorrhage
      period, 2.5 mL of 150 mM glucosamine or equivalent osmolarity of mannitol
      solution was injected intravenously for 10 min. The survival time, mean blood
      pressure, heart rate, and central body temperature were monitored continuously;
      then, the O-GlcNAc levels in heart, brain, liver, and muscle were measured by
      means of Western blot analysis. Glucosamine administration significantly
      increased the survival rate in comparison with mannitol administration
      (percentage of survival after 2 h, 47% vs. 20%; P < 0.05). The mean arterial
      pressure was significantly higher in the glucosamine group for 18 min after
      treatment. The protein O-GlcNAc levels, assessed 30 min after glucosamine
      treatment, were significantly increased in the heart, brain, and liver. These
      data demonstrate that i.v. glucosamine administration improves the survival rate
      after trauma-hemorrhage without resuscitation; this effect may be related to the
      glucosamine-induced increase in protein O-glycosylation. Furthermore, the
      increase in mean arterial pressure may suggest a vasoactive and/or positive
      inotropic effect of glucosamine in hypovolemic shock.

PMID- 17545940
TI  - Trans-sodium crocetinate and hemorrhagic shock.
AB  - Trans-sodium crocetinate (TSC) has been found to alleviate the symptoms of
      hemorrhagic shock in that, after the drug is given to hemorrhaged rats, blood
      pressure rises, elevated lactate levels are reduced, cellular damage in the liver
      and kidney is less, and survival is increased. The mechanism of action proposed
      for TSC is that it increases the diffusion of oxygen through blood plasma and
      into the tissue. The study reported here explores another proposed mechanism, the
      scavenging of free radicals. It is shown that TSC does scavenge radicals and may
      be more efficient than other free-radical scavengers. However, this may not be
      the mechanism of action for TSC during hemorrhagic shock. Not only are the TSC
      concentrations needed for radical scavenging greater than those which provide
      beneficial effects in hemorrhagic shock, but it is also shown that another
      radical scavenger, trolox, has no effect on oxygen consumption during shock.
      Trans-sodium crocetinate clearly holds promise as a useful treatment of
      hemorrhagic shock. Pharmacokinetics data are presented for different modes of
      administration. Initial studies suggest that instillation of TSC into the trachea
      or intramuscular injection may provide useful alternative treatment routes.

PMID- 17545941
TI  - Hypoxia activates c-Jun N-terminal kinase via Rac1-dependent reactive oxygen
      species production in hepatocytes.
AB  - The earliest events after the induction of hemorrhagic shock (HS) are complex and
      poorly understood. We have recently demonstrated that decreased tissue perfusion
      and hypoxia during HS lead to an increased phosphorylation of c-Jun N-terminal
      kinase (JNK) in vivo. The purpose of these investigations was to test the
      hypothesis that hypoxia activates JNK via Rac1-dependent reactive oxygen species
      (ROS) signaling. Mice subjected to HS and resuscitated with Ringer's ethyl
      pyruvate solution (REPS) or N-acetylcysteine (NAC), two scavengers of ROS,
      demonstrated decreased levels of phosphorylated JNK. Exposure of primary mouse
      hepatocytes in culture to 1% oxygen led to increased production of ROS and
      phosphorylation of JNK. The duration of hypoxia correlated with the level of
      generation of ROS and JNK activation. The phosphorylation of JNK was attenuated
      in the presence of ROS scavengers or the nicotinamide adenosine dinucleotide
      phosphate [NDA(P)H] oxidase inhibitor, diphenyleneiodonium (DPI). In addition,
      hypoxia increased activation of Rac1. Inhibition of Rac1 activation by adenoviral
      gene transfer of dominant-negative Rac1 (AdRac1) attenuated both ROS formation
      and JNK activation. Together, these data suggest that ROS generation during
      hypoxia in the liver directly leads to JNK activation in a Rac1-dependent
      process.

PMID- 17545942
TI  - The green tea polyphenol epigallocatechin-3-gallate improves systemic
      hemodynamics and survival in rodent models of polymicrobial sepsis.
AB  - Epigallocatechin-3-gallate (EGCG) is the main polyphenolic flavonoid found in
      green tea. Recent in vitro studies have suggested that EGCG inhibits activation
      of the nuclear factor-kappaB (NF-kappaB) pathway. The NF-kappaB is a
      transcriptional factor required for gene expression of many inflammatory
      mediators, including the inducible isoform of nitric oxide synthase (NOS2).
      Excessive NO production by NOS2 is directly linked to the vasoplegia, shock, and
      mortality associated with sepsis. Accordingly, we hypothesized that EGCG
      administration would inhibit NOS2 gene expression and thereby improve survival in
      a rodent model of polymicrobial sepsis. Polymicrobial sepsis was induced in male
      Sprague-Dawley rats (hemodynamic study) and C57BL6 mice (mortality study) via
      cecal ligation and double puncture (CL2P). Rodents were treated with either EGCG
      (10 mg/kg intraperitoneally) or vehicle at 1 and 6 h after CL2P and every 12 h
      thereafter. In the hemodynamic study, mean arterial blood pressure was monitored
      for 18 h, and rats were killed at 3, 6, and 18 h after CL2P. In the mortality
      study, survival was monitored for 72 h after CL2P in mice. In vehicle-treated
      rodents, CL2P was associated with profound hypotension and greater than 80%
      mortality rate. Epigallocatechin-3-gallate treatment significantly improved both
      the hypotension and survival. In vitro experiments further showed that EGCG
      inhibited activation of NF-kappaB and subsequent NOS2 gene expression in a
      primary culture of rat aortic smooth muscle cells. Epigallocatechin-3-gallate may
      therefore represent a potential nutritional supplement or pharmacologic agent in
      patients with sepsis.

PMID- 17545943
TI  - Molecular signatures of trauma-hemorrhagic shock-induced lung injury: hemorrhage-
      and injury-associated genes.
AB  - The etiology of trauma-hemorrhagic shock (T/HS)-induced acute lung injury has
      been difficult to elucidate because of, at least in part, the inability of in
      vivo studies to separate the noninjurious pulmonary effects of trauma-hemorrhage
      from the tissue-injurious ones. To circumvent this in vivo limitation, we used a
      model of T/HS in which T/HS lung injury was abrogated by dividing the mesenteric
      lymph duct. In this way, it was possible to separate the pulmonary injurious
      response from the noninjurious systemic response to T/HS by comparing the
      pulmonary molecular responses of rats subjected to T/HS, which did and did not
      develop lung injury, with those of nonshocked rats. Using high-density
      oligonucleotide arrays and treatment group comparisons of whole lung tissue
      collected at 3 h after the end of the shock or sham-shock period, 139 of 8,799
      assessed genes were identified by significant analysis of microarrays. Hemorrhage
      without the secondary effects of lung injury modulated the expression of 21 genes
      such as interleukin 1beta, metallothionein-2, and myeloctomatosis oncogene (c
      myc). In response to injury, 42 genes were identified to be differentially
      expressed. Upregulated genes included the L1 retroposon and guanine deaminase,
      whereas downregulated genes included catalase and superoxide dismutase 1. Real
      time polymerase chain reaction confirmed the differential expression for selected
      genes. PathwayAssist analysis identified interleukin 1beta as a central regulator
      of two subpathways of stress response-related genes (c-myc and superoxide
      dismutase 1/catalase) as well as several unrelated genes such as lipoprotein
      lipase. Our model system provided a unique opportunity to distinguish the
      molecular changes associated with T/HS-induced acute lung injury from the
      systemic molecular response to T/HS.

PMID- 17545944
TI  - The hemodynamic effects of dobutamine during reoxygenation after hypoxia: a dose
      response study in newborn pigs.
AB  - Asphyxiated neonates usually have myocardial stunning and hypotension and require
      inotropic support. A randomized controlled study was designed to examine the dose
      response effect of dobutamine (5-20 microg x kg(-1) x min(-1)) on systemic and
      regional circulations and oxygen metabolism in a neonatal swine model of
      hypoxia/reoxygenation. Thirty-eight anesthetized newborn piglets were acutely
      instrumented for continuous monitoring of heart rate, systemic and pulmonary
      arterial pressures, and pulmonary (surrogate for cardiac index), right common
      carotid, and superior mesenteric and left renal arterial flows. After
      stabilization, they were exposed to normocapnic alveolar hypoxia (10%-15% oxygen)
      for 2 h followed by reoxygenation with 100% oxygen for 1 h, then 21% for 3 h.
      Piglets were block randomized to receive dobutamine infusion (5, 10, or 20 microg
      x kg(-1) x min(-1)) or saline (control) at 2 to 4 h of reoxygenation (n = 8
      each). A nonasphyxiated, sham-operated group was included (n = 6). Blood samples
      were collected for blood gas analysis, arterial and venous co-oximetry, and
      plasma lactate concentration determination. At 2-h reoxygenation after hypoxia,
      there was hypotension (systemic arterial pressure, 27 to 36 mmHg) and myocardial
      dysfunction (cardiac index from 178-209 to 134-156 mL x kg(-1) x min(-1)).
      Cardiac index improved significantly with 20 microg x kg(-1) x min(-1) of
      dobutamine (P < 0.05) and modestly in the treatment groups of 5 and 10 microg x
      kg(-1) x min(-1) (P < 0.1) (at 120 min, 172 +/- 35, 160 +/- 30, and 158 +/- 56 mL
      x kg(-1) x min(-1) vs. 119 +/- 33 mL x kg(-1) x min(-1) of controls,
      respectively), with corresponding increases in stroke volume. Pulmonary vascular
      resistance was lower in all dobutamine-treated groups (vs. controls, P < 0.05)
      There were no differences in heart rate, systemic and pulmonary arterial
      pressures, systemic vascular resistance, and regional flows between groups. The
      group of 20 mug.kg.min of dobutamine also had higher systemic oxygen delivery (at
      120 min, 18 +/- 5 vs. 11 +/- 3 O(2) mL x kg(-1) x min(-1) of controls, P < 0.05)
      with no significant differences in systemic oxygen consumption and regional
      oxygen delivery between groups. After the reoxygenation of newborn piglets with
      severe hypoxia, high dose of dobutamine is effective to treat myocardial stunning
      and low cardiac output with no significant effect on blood pressure or regional
      circulation. Further clinical studies are needed to confirm these findings in the
      human neonate.

PMID- 17545945
TI  - Alterations in membrane cholesterol cause mobilization of lipid rafts from
      specific granules and prime human neutrophils for enhanced adherence-dependent
      oxidant production.
AB  - The present study sought to examine the function of membrane lipid rafts in
      adherence-dependent oxidant production in human neutrophils. Rafts are membrane
      domains that are rich in glycosphingolipids and cholesterol and are thought to be
      the foci for formation of signaling complexes in a variety of cells. Disruption
      of lipid rafts by depletion of membrane cholesterol with the chelating agent
      methyl-beta-cyclodextrin (MbetaCD) has been widely used to examine the function
      of lipid rafts. Here, we report that treatment of human neutrophils with MbetaCD
      unexpectedly caused priming of these cells, manifested as enhanced adherence
      dependent oxidant production. Treatment of neutrophils with MbetaCD dose
      dependently increased oxidant production after adhesion to fibronectin-coated
      plates. This priming effect was associated with recruitment of CD11b- and CD66b
      rich raft domains from the specific granules, as determined by immunoblot and
      flow cytometry. Confocal microscopy showed that MbetaCD caused otherwise
      untreated neutrophils to rapidly adhere and spread on fibronectin-coated plates.
      Furthermore, three-dimensional reconstruction microscopy studies showed that
      MbetaCD caused expansion and coalescence of raft domains that covered most of the
      cell surface. These large raft domains expressed CD11b primarily in the core of
      these regions. Our studies demonstrate that cholesterol depletion with MbetaCD
      results in neutrophil priming manifested as enhanced adherence-dependent oxidant
      production. These studies caution against assumption that any observed MbetaCD
      effects are a function of reduced raft formation.

PMID- 17545946
TI  - The reduction of tumor necrosis factor-alpha release and tissue damage by
      pentobarbital in the experimental endotoxemia model.
AB  - Sepsis is the leading cause of death for intensive care patients.
      Lipopolysaccharide (LPS) administration to animals under anesthesia is a strategy
      for the study of uncontrolled release of proinflammatory cytokines. Anesthetics
      have been indicated that they can specially affect immune responses, such as the
      inflammatory response. Pentobarbital is an anesthetic used mainly in animal
      studies. Thus, the effect of pentobarbital on tumor necrosis factor-alpha (TNF
      alpha) release was determined. The results revealed that pentobarbital suppressed
      the expression of TNF-alpha mRNA and its proteins, which may result from the
      decrease in the activities of nuclear factor-kappaB and activator protein 1 and
      the reduction of the expression of p38 mitogen-activated protein kinase by
      pentobarbital. After the inhibitory activity of the pentobarbital for TNF-alpha
      release was proven in vivo, the cytotoxic effects of LPS were examined in vivo
      with or without pentobarbital treatments. In vivo results indicated that plasma
      levels of alanine aminotransferase, aspartate aminotransferase, lactic
      dehydrogenase, creatine kinase, serum urea nitrogen, and amylase decreased
      dramatically in the anesthetic group with pentobarbital administration. Finally,
      the effect of pentobarbital on TNF-alpha-related cell death was monitored in
      vitro, and the results indicated the pentobarbital could directly enhance the
      viabilities of cells under the treatment of TNF-alpha and protected cells from
      apoptosis induced by deferoxamine mesylate-induced hypoxia. These results suggest
      that pentobarbital significantly influences the LPS-induced inflammatory response
      and protects cells from death directly and indirectly induced by TNF-alpha. The
      information provides a perspective to re-evaluate the results of the experiments
      in which animals were anesthetized with pentobarbital. The anti-inflammatory
      effects of the drugs may have been caused by the synergistic effect of
      pentobarbital.

PMID- 17545947
TI  - Regulation of the postburn wound inflammatory response by gammadelta T-cells.
AB  - Healing of the burn injury site is a critical component of the patient's
      successful recovery from this form of trauma. Previous studies from our
      laboratory have demonstrated that gammadelta T-cells via the production of growth
      factors are important in burn wound healing. Nonetheless, the role of these cells
      in burn wound inflammation remains unknown. To study this, wild-type (WT) and
      gammadelta T-cell receptor-deficient (delta TCR) C57BL/6 male mice were subjected
      to burn injury or sham procedure. Wound cells were collected by implantation of
      polyvinyl alcohol sponges beneath the burn site in injured mice or beneath
      uninjured skin in sham mice. At 3 days after injury, infiltrating cells, wound
      fluid, and skin were collected for analysis. Burn injury markedly increased skin
      tumor necrosis factor-alpha (TNF-alpha) and monocyte chemoattractant protein 1
      levels. In WT mice, the numbers of infiltrating cells were similar between
      nonburn wounds and burn wounds. In contrast, deltaTCRmice displayed a 6-fold
      reduction in the cellular infiltrate. Burn injury in WT mice caused a marked
      increase in burn wound TNF-alpha, monocyte chemoattractant protein 1, and
      interleukin 6 content as compared with nonburn wounds, whereas in delta TCRmice,
      the burn-induced increase of TNF-alpha and interleukin 6 was not observed. The
      wound cell infiltrate at 3 days postinjury was devoid of gammadelta T-cells in WT
      mice. It was predominately of myeloid origin expressing high levels of CD11b and
      F4/80. In conclusion, these findings suggest that resident gammadelta T-cells are
      important in the recruitment of inflammatory cells and regulation of the
      inflammatory response at the wound site after thermal injury.

PMID- 17545948
TI  - Hydroxyethyl starch normalizes platelet and leukocyte adhesion within pulmonary
      microcirculation during LPS-induced endotoxemia.
AB  - Growing evidence supports substantial pathophysiological impact of platelets and
      their interactions on the development of septic lung failure. We developed a rat
      model of endotoxemia for direct in situ visualization of pulmonary
      microcirculation by in vivo fluorescence videomicroscopy. Male Sprague-Dawley
      rats were assigned to control, endotoxemia (Escherichia coli LPS, 15 mg/kg,
      i.v.), and fluid management for treatment of LPS-induced hypovolemia (Ringer
      lactate, hydroxyethyl starch [HES] 6%) groups (n = 7 each). Leukocytes were
      labeled in vivo by rhodamine, and 5 x 10(6) Calcein-AM-labeled nonactivated
      platelets were injected. Microcirculatory parameters (vessel diameter,
      ventilation-perfusion ratio) and adhesive characteristics of platelets and
      leukocytes (velocity, rolling, sticking) within the pulmonary microcirculation
      were quantified after endotoxin application under various regimens of fluid
      substitution for 60 min. A reduction of cell velocity and enhanced cell adhesion
      was seen in leukocytes and platelets (P < 0.05) after LPS injection. Fluid
      treatment with HES 6% resulted in a significant increase of platelet's velocity
      compared with the LPS group (442.86 +/- 20.60 vs. 343.93 +/- 11.17; P < 0.05),
      whereas Ringer lactate showed no beneficial effects. Similarly, HES 6% normalized
      LPS-induced platelet rolling and sticking as well as alterations in ventilation
      perfusion ratio. Using direct visualization of the pulmonary microcirculation, we
      observed that platelet and leukocyte interactions are enhanced in the lung during
      LPS endotoxemia. Fluid therapy with HES 6% seems to have restorative effects on
      these cellular functions within the pulmonary microcirculation.

PMID- 17545949
TI  - Role of p38 mitogen-activated protein kinase on cardiac dysfunction after
      hemorrhagic shock in rats.
AB  - Cardiac dysfunction is a well-known complication of hemorrhagic shock as a
      consequence of local inflammatory response. Several studies have indicated that
      p38 mitogen-activated protein kinase (MAPK) is a key mediator in organ
      dysfunction that is associated with the inflammatory state through the activation
      of proinflammatory cytokines such as TNF-alpha and IL-1beta. Whether the same
      applies to cardiac dysfunction after hemorrhagic shock has not been clearly
      determined. Therefore, in this study, the role of p38 MAPK on cardiac dysfunction
      after hemorrhagic shock was studied up to 5 h after a hemorrhage using FR167653,
      a specific inhibitor of p38 MAPK phosphorylation. The p38 MAPK phosphorylation,
      the cardiac mRNA expressions of TNF-alpha and IL-1beta, and intracardiac serum
      concentrations of each cytokine and creatine phosphokinase-MB isozyme increased
      after a hemorrhage. Activated neutrophil accumulation in the heart, histological
      inflammation-related injuries, and frequent ventricular arrhythmia were observed
      in the late phase after hemorrhagic shock. FR167653 inhibited these hemorrhagic
      changes except the induction of the primary hypotensive state. These results
      demonstrate that p38 MAPK phosphorylation in hemorrhagic shock plays an important
      role in the cardiac expression of the proinflammatory cytokines and in the
      development of cardiac dysfunction relative to the inflammatory responses.

PMID- 17545950
TI  - Is Magnet a money-maker?

PMID- 17545951
TI  - Push parameters forward using evidence-based approaches.

PMID- 17545952
TI  - Novel therapeutics for schizophrenia: targeting glycine modulation of NMDA
      glutamate receptors.

PMID- 17545953
TI  - Psychiatric comorbidity in 36 adults with mitochondrial cytopathies.
AB  - INTRODUCTION: Mitochondria are intracellular organelles involved in adenosine
      triphosphate production. The literature has established the presence of
      mitochondrial dysfunction in some subjects with psychiatric disorders. Also,
      there are multiple reports of patients with mitochondrial dysfunction who have
      various psychiatric disorders. Although the literature on mitochondrial
      dysfunction and its relation to psychiatric disorders is growing, there remain
      many unanswered questions. OBJECTIVE: To review subjects with mitochondrial
      cytopathies for prevalence of psychiatric comorbidity. METHODS: For this study,
      36 adults were interviewed. The Mini International Neuropsychiatric Interview and
      the Short-Form 36 Health Survey, version 1 were used. RESULTS: Lifetime diagnoses
      included 54% major depressive disorder, 17% bipolar disorder, and 11% panic
      disorder. These prevalence rates are compared with the general population and
      subjects with cancer and epilepsy. Subjects with a comorbid psychiatric diagnosis
      were older (P=.05), had more hospital admissions (P=.02), more medical conditions
      (P=.01), and lower quality of life (P=.01) than subjects with mitochondrial
      disease alone. CONCLUSION: Clinicians caring for persons with mitochondrial
      cytopathies should note the high prevalence of psychiatric problems. Also, this
      comorbidity might have etiological and therapeutic implications.

PMID- 17545954
TI  - An open-label trial of divalproex extended-release in the treatment of borderline
      personality disorder.
AB  - INTRODUCTION: Borderline personality disorder (BPD) is associated with several
      symptoms, including impulsivity, aggression, and intense unstable affect, which
      can be targeted with anticonvulsant agents. Divalproex extended-release (ER) is
      used widely in clinical practice, which leads to the question of its efficacy and
      tolerability in treating BPD. METHODS: This study assessed the efficacy and
      tolerability of divalproex ER in 20 adult outpatients with Diagnostic and
      Statistical Manual of Mental Disorders, Fourth Edition BPD via a 12-week open
      label trial. Primary outcome measures included the Clinical Global Impression
      Improvement (CGI-I) scale and the Global Assessment Scale. Secondary outcome
      measures assessed aggression (Aggression Questionnaire, Overt Aggression Scale
      Modified); affective disturbance (Affective Intensity Measure, Affective Lability
      Scale); dissociation (Dissociative Experiences Scale); and general
      psychopathology (Symptom-Checklist 90-Revised). RESULTS: Thirteen subjects were
      male and seven were female with a mean age of 37.0+/-11.3 years. Treatment was
      associated with statistically significant improvement on the CGI-I, the Global
      Assessment Scale, the Overt Aggression Scale-Modified irritability subscale, and
      the Aggression Questionnaire. A trend toward significant improvement was observed
      on the Affective Intensity Measure. Seven out of 10 completers (70%) were
      treatment responders, with an endpoint CGI-I of 2 (much improved) or 1 (very much
      improved). There was no significant decline in affective lability or in
      dissociation. One participant discontinued treatment due to adverse events.
      CONCLUSION: These findings support that divalproex ER is an efficacious and well
      tolerated pharmacologic agent for BPD, with the additional advantage of single
      daily dosing at bedtime. Placebo-controlled trials are needed for replication.

PMID- 17545955
TI  - A case of resolution of an acute psychotic episode after high fever.
AB  - Fever (pyretotherapy) was used for psychosis during the turn of the 19th century,
      but pyretotherapy (ie, the treatment of a disorder by inducing fever) fell out of
      use after the introduction of convulsive methods. Here, we report on a case of
      schizoaffective disorder and review classical and recent literature on fever and
      psychosis. The patient developed auditory hallucinations, persecutory delusional
      ideas, and was terrified soon upon his arrival in a foreign country. After being
      treated for 12 days with olanzapine and haloperidol, he developed a fever due to
      urinary infection; his creatine phosphokinase levels were high, prompting the
      suspension of antipsychotics. Psychotic symptom resolution followed immediately
      fever abatement. Antipsychotics were reintroduced at lower dosages. He was
      discharged asymptomatic with a prescription of olanzapine 15 mg/day and
      haloperidol 3 mg/day. The time course of symptom resolution in this patient
      suggests that fever had a beneficial role in this case. The associations between
      body temperature changes and psychotic symptoms need to be further studied.

PMID- 17545956
TI  - Problematic Internet use: clinical implications.
AB  - Impulse-control disorders have received relatively little attention from the
      mental health community. An increasing awareness of the prevalence and impact of
      these disorders is emerging. Among impulse-control disorders, problematic
      Internet use has been considered and examined. Prevalence estimate studies
      indicate that problematic Internet use is experienced across geographic locations
      by many individuals of diverse backgrounds. This review examines problematic
      Internet use from epidemiological and clinical perspectives. Clinicians should be
      familiar with the extent of problematic Internet use and the data regarding the
      efficacies and tolerabilities of available treatments.

PMID- 17545957
TI  - Does obsessive-compulsive personality disorder belong within the obsessive
      compulsive spectrum?
AB  - It has been proposed that certain Diagnostic and Statistical Manual of Mental
      Disorders, Fourth Edition Axis I disorders share overlapping clinical features,
      genetic contributions, and treatment response and fall within an "obsessive
      compulsive" spectrum. Obsessive-compulsive personality disorder (OCPD) resembles
      obsessive-compulsive disorder (OCD) and other spectrum disorders in terms of
      phenomenology, comorbidity, neurocognition, and treatment response. This article
      critically examines the nosological profile of OCPD with special reference to OCD
      and related disorders. By viewing OCPD as a candidate member of the obsessive
      compulsive spectrum, we gain a fresh approach to understanding its neurobiology,
      etiology, and potential treatments.

PMID- 17545958
TI  - The brain as a substrate for psychotropic therapeutics. Introduction.

PMID- 17545959
TI  - Special considerations in diagnosing and treating attention-deficit/hyperactivity
      disorder.
AB  - Attention-deficit/hyperactivity disorder (ADHD) is a prevalent chronic condition
      that affects people of all ages, including young children, school-aged children,
      adolescents, and adults. Symptoms can be noted as early as preschool age, tend to
      progress into functional impairment and behavioral problems in later childhood,
      and typically persist into adulthood. Contrary to previous belief, the disorder
      does not resolve with puberty for the majority of children; rather, the symptoms
      are manifested differently throughout the lifecycle. Presentation in adults is
      heavily biased toward inattentive symptoms, which are less likely to draw notice
      than hyperactive or impulsive symptoms and may contribute to the underrecognition
      of ADHD in this patient population. Diagnosis is particularly difficult due in
      large part to the pronounced comorbidity of psychiatric disorders in this patient
      population. Identification may be even more difficult in adults than children as
      the diagnostic criteria are not as clear, adults have difficulty remembering
      symptoms prior to 7 years of age, and there is a high prevalence of comorbid
      psychiatric disorders in adults. Early identification and treatment of symptoms
      of ADHD in preschool-age children is essential to effective long-term management
      of the disorder. Both medication and behavioral treatments appear to alleviate
      the symptoms of ADHD, and evidence suggests that discontinuation of treatment
      leads to the reemergence of the condition. Efforts are currently continuing
      toward understanding the genetic underpinnings of ADHD. This expert review
      supplement will address the prevalence, comorbidity, treatment issues, and
      special considerations surrounding ADHD management throughout each stage of the
      lifecycle beginning with ADHD in preschool-aged children, continuing with school
      aged children and adolescents, and ending with adulthood.

PMID- 17545960
TI  - Evidence for immune etiology in clozapine-induced thrombocytopenia of 40 months'
      duration: a case report.
AB  - Platelet dysfunction and thrombocytopenia rarely occur during clozapine therapy,
      but constitute an important source of morbidity and mortality if they are not
      detected and therapy is discontinued. The manufacturer recommends discontinuing
      clozapine when the platelet count falls below 100,000/muL and resuming therapy
      when the count returns to within normal range (150,000-450,000/muL). If
      thrombocytopenia recurs, clozapine should be permanently discontinued. The
      authors report a rare case of long-term thrombocytopenia persisting 40 months
      postclozapine treatment. In addition, increased in vitro platelet [14C]serotonin
      release was observed in the presence of the drug, suggesting an immune-related
      cause for the thrombocytopenia.

PMID- 17545961
TI  - Dyskinesias differentiate autistic disorder from catatonia.
AB  - Autistic disorder and catatonia are neuropsychiatric syndromes defined by
      impairments in social interaction, communication, and restricted, stereotypical
      motor routines. Assessments of children with these disorders are typically
      restricted in scope by the patients' limited ability to comprehend directions.
      The authors performed systematic assessments of dyskinesias on six prepubertal
      boys with autistic disorder and mental retardation and on one adolescent male
      with catatonia to determine if this type of information could be routinely
      obtained. The boys with autistic disorder had more stereotypies and tics, a
      greater degree of akathisia and hyperactivity, and more compulsions than the
      adolescent with catatonia. Catatonia was associated with catalepsy and dystonic
      postures. The authors conclude that the diagnostic accuracy and specificity of
      neuropsychiatric syndromes may be enhanced by the systematic assessment of the
      dyskinesias associated with each condition.

PMID- 17545962
TI  - Pharmacotherapeutic options in the treatment of comorbid depression and anxiety.
AB  - Although anxiety and mood disorders are listed as separate disorders in the
      Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, they
      frequently coexist. They may be expressed phenotypically as comorbidities or as
      the provisional entity mixed anxiety-depressive disorder. Patients with both
      anxiety and depression are more symptomatic, use more health care resources, and
      have a worse prognosis than those with a single disorder. Recognizing and
      treating these patients are challenges for physicians because the symptoms of the
      two disorders often overlap. Administration of effective treatment, comprising
      both anxiolytic and antidepressant effects, can reduce patient distress and
      disability, as well as inappropriate utilization of medical services. Medications
      such as tricyclic antidepressants, selective serotonin reuptake inhibitors,
      nefazodone, venlafaxine XR (extended release) and mirtazapine, are highly
      effective in treating comorbid depression and anxiety. These newer agents now
      represent the pharmacotherapeutic treatments of choice for the comorbid
      conditions.

PMID- 17545963
TI  - Onset of obsessive-compulsive disorder: premorbid conditions and prodromal phase.
AB  - This article focuses on the clinical onset of obsessive-compulsive disorder
      (OCD), specifically addressing the age of onset, gradual and acute onset, and
      whether there are some types of premorbid conditions or a prodromal phase that
      predispose individuals to the onset of OCD. Clinical and epidemiological studies
      have come to different conclusions regarding age at onset as well as regarding
      differences between the sexes. Data gleaned from research to date have
      demonstrated a relationship between OCD and obsessive-compulsive personality
      disorder (OCPD), although OCPD does not appear to be the more prevalent
      personality disorder among patients with OCD. Preliminary research has suggested
      that Axis I disorders may predispose individuals to OCD onset; however, the
      significance of this relationship remains to be clarified. Evidence of the
      association between OCD and subthreshold obsessive-compulsive syndrome suggests
      that these disorders lie on a continuum of severity, with some cases developing
      OCD while others do not.

PMID- 17545964
TI  - The role of recent life events in the onset of obsessive-compulsive disorder.
AB  - Although many investigations into the onset of obsessive-compulsive disorder
      (OCD) suggest the occurrence of potential life events as triggering factors, such
      an association has not been well studied to date. The purpose of the present
      paper is to review the literature on OCD onset in order to determine whether OCD
      is triggered by recent life events, what specific events may serve as triggers,
      and the clinical and research implications of these factors. Overall, the
      available studies do not consistently support the theory that OCD is triggered by
      specific antecedent life events. However, there is a body of evidence to support
      the theory that the specific life events of pregnancy and birth of a child can
      trigger OCD. This apparent association has led to the investigation of certain
      neurohormonal factors, including changes in estrogen or oxytocin levels, that may
      be of etiopathogenetic significance in OCD. Confirming such associations may
      allow clinicians to provide more targeted preventive and therapeutic
      interventions.

PMID- 17545965
TI  - Ocular langerhans cell histiocytosis.

PMID- 17545966
TI  - Combined treatment of a juxtapapillary retinal capillary haemangioma with
      intravitreal bevacizumab and photodynamic therapy.

PMID- 17545967
TI  - Protocols for growth and development of Dictyostelium discoideum.
AB  - Dictyostelium discoideum, a unicellular organism capable of developing into a
      multicellular structure, is a powerful model system to study a variety of
      biological processes. Because it is inexpensive and relatively easy to grow,
      Dictyostelium is also frequently used in teaching laboratories. Here we describe
      conditions for successfully growing and developing Dictyostelium cells and
      methods for long-term storage of Dictyostelium amoebae and spores.

PMID- 17545968
TI  - Transformation of Dictyostelium discoideum with plasmid DNA.
AB  - DNA-mediated transformation is one of the most widely used techniques to study
      gene function. The eukaryote Dictyostelium discoideum is amenable to numerous
      genetic manipulations that require insertion of foreign DNA into cells. Here we
      describe two commonly used methods to transform Dictyostelium cells: calcium
      phosphate precipitation, resulting in high copy number transformants; and
      electroporation, an effective technique for producing single integration events
      into genomic DNA. Single integrations are required for gene disruption by
      homologous recombination. We also discuss how different selection markers affect
      vector copy number in transformants and explain why blasticidin has become the
      preferred selectable marker for making gene knockouts. Both procedures can be
      accomplished in less than 2 h of hands-on time; however, the calcium phosphate
      precipitation method contains several incubations, including one of at least 4 h,
      so the total time required for the transformation is approximately 8 h.

PMID- 17545969
TI  - A reliable general purpose method for extracting genomic DNA from Dictyostelium
      cells.
AB  - In this protocol, we present a standard method for extracting DNA from cells of
      the social amoeba Dictyostelium discoideum. While this procedure is similar to
      other phenol:chloroform-based purification methods, it is modified to account for
      the high level of carbohydrate and nucleases found in Dictyostelium cells.
      Genomic DNA can be isolated from wild-type and genetically modified cells using
      the described protocol, allowing molecular genetic analyses to be performed.
      Following cell lysis, nucleic acid extraction, and precipitation, the isolated
      DNA is suitable for digestion by restriction enzymes, amplification by PCR and
      Southern blotting. This procedure takes approximately 3 h to complete.

PMID- 17545970
TI  - A general purpose method for extracting RNA from Dictyostelium cells.
AB  - Here we present a protocol for the extraction of RNA from Dictyostelium
      discoideum. Dictyostelium is a social amoeba that undergoes a basic developmental
      program, and therefore analysis of RNA levels over a time course is a commonly
      used technique. This procedure is similar to other guanidine thiocyanate-based
      methods; however, it has been adjusted because of the large quantities of
      carbohydrate and nucleases found in Dictyostelium cells. After cell lysis and
      phenol:chloroform extraction, the resulting high-quality RNA isolated with the
      described protocol allows the molecular genetic analysis of wild-type and
      genetically modified cells. The purified RNA can be used for analyses such as
      northern blotting, RT-PCR and microarrays. This procedure requires approximately
      2 h to complete.

PMID- 17545971
TI  - Peptide arrays on cellulose support: SPOT synthesis, a time and cost efficient
      method for synthesis of large numbers of peptides in a parallel and addressable
      fashion.
AB  - Peptide synthesis on cellulose using SPOT technology allows the parallel
      synthesis of large numbers of addressable peptides in small amounts. In addition,
      the cost per peptide is less than 1% of peptides synthesized conventionally on
      resin. The SPOT method follows standard fluorenyl-methoxy-carbonyl chemistry on
      conventional cellulose sheets, and can utilize more than 600 different building
      blocks. The procedure involves three phases: preparation of the cellulose
      membrane, stepwise coupling of the amino acids and cleavage of the side-chain
      protection groups. If necessary, peptides can be cleaved from the membrane for
      assays performed using soluble peptides. These features make this method an
      excellent tool for screening large numbers of peptides for many different
      purposes. Potential applications range from simple binding assays, to more
      sophisticated enzyme assays and studies with living microbes or cells. The time
      required to complete the protocol depends on the number and length of the
      peptides. For example, 400 9-mer peptides can be synthesized within 6 days.

PMID- 17545972
TI  - A liquid chromatography-mass spectrometry method for the quantitative analysis of
      urinary endogenous estrogen metabolites.
AB  - The ability to measure estrogen metabolites (EMs) quantitatively is important for
      investigating their individual roles in cancer screening, treatment and
      prevention, as well as in a host of other hormone-related disorders. In this
      protocol we describe a method that is capable of quantitating 15 distinct EMs in
      urine. Endogenous EMs are quantitatively measured using a liquid chromatography
      tandem mass spectrometry method in which the spectrometer operates in a selected
      reaction monitoring mode. This method is capable of quantifying estrone and its 2
      , and 4- and 16alpha-hydroxy and its 2-, 4-methoxy derivatives, and 2
      hydroxyestrone-3-methyl ether; 17beta-estradiol and its 2-hydroxy, and 2- and 4
      methoxy derivates, and estriol, 16-epiestriol, 17-epiestriol, and 16
      ketoestradiol. The method requires only 0.5 ml of urine and approximately 60
      urine samples can be quantitatively analyzed per week.

PMID- 17545973
TI  - Isolation of renal proximal tubular brush-border membranes.
AB  - This protocol describes a method for the isolation and purification of renal
      proximal tubular brush-border membranes in high yield and high purity. Based on a
      different reactivity of the brush-border membrane compared to other cellular
      membranes with divalent cations, such as Mg2+, purified membrane vesicles can be
      obtained after a few differential centrifugation steps (within approximately 3 h)
      that are suitable for in vitro studies, such as transport experiments or protein
      and lipid analysis.

PMID- 17545974
TI  - Versatile synthesis of oligodeoxyribonucleotide-oligospermine conjugates.
AB  - A protocol for the rapid, automated synthesis of oligospermine-oligonucleotide
      sequences is described. To this end, a protected spermine phosphoramidite
      derivative was synthesized in six steps from spermine and used as the fifth
      synthon in an oligonucleotide synthesizer. Parameters were optimized to reach
      greater than 95% coupling yields. Cationic oligonucleotides show enhanced
      hybridization and strand invasion properties, and hence are an alternative to
      conventional oligonucleotides for molecular biology, diagnostic and potential
      therapeutic applications. A multi-gram-scale synthesis of the spermine
      phosphoramidite allowing several hundred coupling steps takes 2-3 weeks.
      Oligonucleotide synthesis and purification takes approximately 3 d.

PMID- 17545975
TI  - Identifying specificity profiles for peptide recognition modules from phage
      displayed peptide libraries.
AB  - Signaling complexes usually involve multidomain proteins containing catalytic
      domains and peptide recognition modules (PRMs), which mediate protein-protein
      interactions and assemble complexes by binding to ligands containing a core
      sequence motif. Concomitant to large-scale physical interaction screening,
      considerable effort has been devoted toward the elucidation of consensus profiles
      for common PRMs. We describe herein a robust and proven protocol to generate
      consensus profiles for PRMs using phage-displayed peptide libraries. The initial
      phase of the protocol entails the cloning, expression and purification of PRMs as
      fusion proteins, in addition to the construction of highly diverse phage
      displayed peptide libraries. The affinity selection process described thereafter
      enables a single researcher to efficiently probe the recognition profiles of
      numerous PRMs in a 1 week time period.

PMID- 17545976
TI  - AFLP technology for DNA fingerprinting.
AB  - The AFLP technique is a powerful DNA fingerprinting technology applicable to any
      organism without the need for prior sequence knowledge. The protocol involves the
      selective PCR amplification of restriction fragments of a total digest of genomic
      DNA, typically obtained with a mix of two restriction enzymes. Two limited sets
      of AFLP primers are sufficient to generate a large number of different primer
      combinations (PCs), each of which will yield unique fingerprints. Visualization
      of AFLP fingerprints after gel electrophoresis of AFLP products is described
      using either a conventional autoradiography platform or an automated LI-COR
      system. The AFLP technology has been used predominantly for assessing the degree
      of variability among plant cultivars, establishing linkage groups in crosses and
      saturating genomic regions with markers for gene landing efforts. AFLP fragments
      may also be used as physical markers to determine the overlap and positions of
      genomic clones and to integrate genetic and physical maps. Crucial
      characteristics of the AFLP technology are its robustness, reliability and
      quantitative nature. This latter feature has been exploited for co-dominant
      scoring of AFLP markers in sample collections such as F2 or back-cross
      populations using appropriate AFLP scoring software. This protocol can be
      completed in 2-3 d.

PMID- 17545977
TI  - AFLP-based transcript profiling (cDNA-AFLP) for genome-wide expression analysis.
AB  - Although DNA microarrays are currently the standard tool for genome-wide
      expression analysis, their application is limited to organisms for which the
      complete genome sequence or large collections of known transcript sequences are
      available. Here, we describe a protocol for cDNA-AFLP, an AFLP-based transcript
      profiling method that allows genome-wide expression analysis in any species
      without the need for prior sequence knowledge. In essence, the cDNA-AFLP method
      involves reverse transcription of mRNA into double-stranded cDNA, followed by
      restriction digestion, ligation of specific adapters and fractionation of this
      mixture of cDNA fragments into smaller subsets by selective PCR amplification.
      The resulting cDNA-AFLP fragments are separated on high-resolution gels, and
      visualization of cDNA-AFLP fingerprints is described using either a conventional
      autoradiography platform or an automated LI-COR system. Observed differences in
      band intensities between samples provide a good measure of the relative
      differences in the gene expression levels. Identification of differentially
      expressed genes can be accomplished by purifying cDNA-AFLP fragments from
      sequence gels and subsequent sequencing. This method has found widespread use as
      an attractive technology for gene discovery on the basis of fragment detection
      and for temporal quantitative gene expression analysis. The protocol can be
      completed in 3-4 d.

PMID- 17545978
TI  - Tandem orthogonal proteolysis-activity-based protein profiling (TOP-ABPP)--a
      general method for mapping sites of probe modification in proteomes.
AB  - Activity-based protein profiling (ABPP) utilizes active site-directed chemical
      probes to monitor the functional state of enzymes directly in native biological
      systems. Identification of the specific sites of probe labeling on enzymes
      remains a major challenge in ABPP experiments. In this protocol, we describe an
      advanced ABPP platform that utilizes a tandem orthogonal proteolysis (TOP)
      strategy coupled with mass spectrometric analysis to simultaneously identify
      probe-labeled proteins together with their exact sites of probe modification.
      Elucidation of probe modification sites reveals fundamental insights into the
      molecular basis of specific probe-protein interactions. The TOP-ABPP method can
      be applied to any type of proteomic sample, including those derived from in vitro
      or in vivo labeling experiments, and is compatible with a variety of chemical
      probe structures. Completion of the entire protocol, including chemical synthesis
      of key reagents, requires approximately 8-10 days.

PMID- 17545979
TI  - Synthesis and utilization of reversible and irreversible light-activated
      nanovalves derived from the channel protein MscL.
AB  - This protocol details the chemical modification of the mechanosensitive channel
      of large-conductance (MscL) channel protein into a light-activated nanovalve and
      its utilization for triggered delivery in synthetic liposomal vesicles. It is
      based on charge-induced activation of this otherwise mechanosensitive channel by
      covalent attachment to the protein of rationally designed synthetic
      functionalities. In the dark, these functionalities will be uncharged and the
      channel will stay closed, but UV illumination will cause their ionization and
      trigger channel activity. In the case of reversible activation, subsequent
      illumination with visible light will neutralize the charge, causing the channel
      to close. The protocol includes synthesis of light-responsive compounds, protein
      isolation and its chemical labeling, reconstitution of the protein into
      artificial membranes, its analysis at the single-molecule level and its
      application in liposomal delivery. The whole protocol takes 4 days. Unlike
      mutagenesis, this method allows the introduction of custom-designed functional
      groups.

PMID- 17545980
TI  - Detection of proteins using a colorimetric bio-barcode assay.
AB  - The colorimetric bio-barcode assay is a red-to-blue color change-based protein
      detection method with ultrahigh sensitivity. This assay is based on both the bio
      barcode amplification method that allows for detecting miniscule amount of
      targets with attomolar sensitivity and gold nanoparticle-based colorimetric DNA
      detection method that allows for a simple and straightforward detection of
      biomolecules of interest (here we detect interleukin-2, an important biomarker
      (cytokine) for many immunodeficiency-related diseases and cancers). The protocol
      is composed of the following steps: (i) conjugation of target capture molecules
      and barcode DNA strands onto silica microparticles, (ii) target capture with
      probes, (iii) separation and release of barcode DNA strands from the separated
      probes, (iv) detection of released barcode DNA using DNA-modified gold
      nanoparticle probes and (v) red-to-blue color change analysis with a graphic
      software. Actual target detection and quantification steps with premade probes
      take approximately 3 h (whole protocol including probe preparations takes
      approximately 3 days).

PMID- 17545981
TI  - Extraction, purification and analysis of histones.
AB  - Histone proteins are the major protein components of chromatin, the
      physiologically relevant form of the genome (or epigenome) in all eukaryotic
      cells. Chromatin is the substrate of many biological processes, such as gene
      regulation and transcription, replication, mitosis and apoptosis. Since histones
      are extensively post-translationally modified, the identification of these
      covalent marks on canonical and variant histones is crucial for the understanding
      of their biological significance. Many different biochemical techniques have been
      developed to purify and separate histone proteins. Here, we present standard
      protocols for acid extraction and salt extraction of histones from chromatin;
      separation of extracted histones by reversed-phase HPLC; analysis of histones and
      their specific post-translational modification profiles by acid urea (AU) gel
      electrophoresis and the additional separation of non-canonical histone variants
      by triton AU(TAU) and 2D TAU electrophoresis; and immunoblotting of isolated
      histone proteins with modification-specific antibodies.

PMID- 17545982
TI  - Single-strand conformation polymorphism analysis using capillary array
      electrophoresis for large-scale mutation detection.
AB  - This protocol describes capillary array electrophoresis single-strand
      conformation polymorphism (CAE-SSCP), a screening method for detection of unknown
      and previously identified mutations. The method detects 98% of mutations in a
      sample material and can be applied to any organism where the goal is to determine
      genetic variation. This protocol describes how to screen for mutations in 192
      singleplex or up to 768 multiplex samples over 3 days. The protocol is based on
      the principle of sequence-specific mobility of single-stranded DNA in a native
      polymer, and covers all stages in the procedure, from initial DNA purification to
      final CAE-SSCP data analysis, as follows: DNA is purified, followed by PCR
      amplification using fluorescent primers. After PCR amplification, double-stranded
      DNA is heat-denatured to separate the strands and subsequently cooled on ice to
      avoid reannealing. Finally, samples are analyzed by capillary electrophoresis and
      appropriate analysis software.

PMID- 17545983
TI  - Detection of in vivo protein-DNA interactions using DamID in mammalian cells.
AB  - Understanding gene regulatory networks in mammalian cells requires detailed
      knowledge of protein-DNA interactions. Commonly used methods for genome-wide
      mapping of these interactions are based on chromatin immunoprecipitation.
      However, these methods have some drawbacks, such as the use of crosslinking
      reagents, the need for highly specific antibodies and relatively large amounts of
      starting material. We present DamID, an alternative technique to map genome-wide
      occupancy of interaction sites in vivo, that bypasses these limitations. DamID is
      based on the expression of a fusion protein consisting of a protein of interest
      and DNA adenine methyltransferase (Dam). This leads to methylation of adenines
      near sites where the protein of interest interacts with the DNA. These methylated
      sequences are subsequently amplified by a methylation-specific PCR protocol and
      identified by hybridization to microarrays. Using DamID, genome-wide maps of the
      binding of DNA-interacting proteins in mammalian cells can be constructed
      efficiently. Depending on the strategy used for expression of the Dam-fusion
      proteins, genome-wide binding maps can be obtained in as little as 2 weeks.

PMID- 17545984
TI  - Application of direct current electric fields to cells and tissues in vitro and
      modulation of wound electric field in vivo.
AB  - It has long been known that cells can be induced to migrate by the application of
      small d.c. electric fields (EFs), a phenomenon referred to as galvanotaxis. We
      recently reported some significant effects of electric signals of physiological
      strength in guiding cell migration and wound healing. We present here protocols
      to apply an EF to cells or tissues cultured in an electrotactic chamber. The
      chamber can be built to allow controlled medium flow to prevent the potential
      development of chemical gradients generated by the EFs. It can accommodate cells
      on planar culture or tissues in 3D gels. Mounted on an inverted microscope, this
      setup allows close and well-controlled observation of cellular responses to
      electric signals. As similar EFs are widely present during development and wound
      healing, this experimental system can be used to simulate and study cellular and
      molecular responses to electric signals in these events.

PMID- 17545985
TI  - Isolation and culture of adult neurons and neurospheres.
AB  - Here we present a protocol for extraction and culture of neurons from adult rat
      or mouse CNS. The method proscribes an optimized protease digestion of slices,
      control of osmolarity and pH outside the incubator with Hibernate and density
      gradient separation of neurons from debris. This protocol produces yields of
      millions of cortical, hippocampal neurons or neurosphere progenitors from each
      brain. The entire process of neuron isolation and culture takes less than 4 h.
      With suitable growth factors, adult neuron regeneration of axons and dendrites in
      culture proceeds over 1-3 weeks to allow controlled studies in pharmacology,
      electrophysiology, development, regeneration and neurotoxicology. Adult
      neurospheres can be collected in 1 week as a source of neuroprogenitors ethically
      preferred over embryonic or fetal sources. This protocol emphasizes two
      differences between neuron differentiation and neurosphere proliferation:
      adhesion dependence and the differentiating power of retinyl acetate.

PMID- 17545986
TI  - In vitro methods to prepare astrocyte and motoneuron cultures for the
      investigation of potential in vivo interactions.
AB  - This protocol details methods to isolate and purify astrocytes and motoneurons
      (MNs) from the chick lumbar spinal cord. In addition, an approach to study the
      influences of astrocyte secreted factors on MNs is provided. Astrocytes are
      isolated between embryonic days 10 and 12 (E10-12), propagated in serum (2-3 h)
      and differentiated in chemically defined medium (3-4 h). When prepared according
      to this protocol, astrocyte cultures are more than 98% pure when assessed using
      the astrocyte-specific markers glial fibrillary acidic protein (GFAP) and
      S100beta. MNs are isolated between E5.5 and 6.0 (3-4 h) using a procedure that
      takes selective advantage of the large size of these cells. These cultures can be
      maintained using individual trophic factors, target-derived factors or astrocyte
      derived factors, the preparation of which is also described (5-6 h). All or part
      of these techniques can be used to investigate a variety of processes that occur
      during nervous system development and disease or after injury.

PMID- 17545987
TI  - Market economy for scientists.

PMID- 17545988
TI  - What is anonymous?

PMID- 17545989
TI  - Animal rights, human wrongs? Introduction to the Talking Point on the use of
      animals in scientific research.

PMID- 17545990
TI  - Animal research: a moral science. Talking Point on the use of animals in
      scientific research.

PMID- 17545991
TI  - The ethics of animal research. Talking Point on the use of animals in scientific
      research.

PMID- 17545992
TI  - Inevitable or avoidable? Despite the lessons of history, the world is not yet
      ready to face the next great plague.

PMID- 17545993
TI  - Bioethics goes global. A growing coalition of scientists, ethicists and wealthy
      benefactors is turning its attention to global health problems.

PMID- 17545994
TI  - The ins and outs of tRNA transport.

PMID- 17545995
TI  - SUMO junction-what's your function? New insights through SUMO-interacting motifs.
AB  - The small ubiquitin-like modifier, SUMO, can be covalently linked to specific
      proteins and many substrates carrying this modification have been identified.
      However, for some proteins, the role that SUMO modification imparts remains
      obscure. Our understanding of SUMO biology and function has been significantly
      advanced by the recent discovery of proteins and protein domains that contain
      SUMO-interacting motifs (SIMs), which interact non-covalently with SUMO. Unlike
      the motifs and domains that mediate ubiquitin binding, the diversity of SIMs
      seems limited. Nevertheless, SIMs have already increased our understanding of how
      SUMO affects DNA repair, transcriptional activation, nuclear body formation and
      protein turnover. This review takes a detailed look at how SIMs were identified,
      how they specifically bind to SUMO, their crucial roles in multi-step enzymatic
      processes, and how they direct the assembly and disassembly of dimeric and
      multimeric protein complexes.

PMID- 17545998
TI  - Titanium dioxide as a chemo-affinity solid phase in offline phosphopeptide
      chromatography prior to HPLC-MS/MS analysis.
AB  - We have developed a new offline chromatographic approach for the selective
      enrichment of phosphorylated peptides that is directly compatible with subsequent
      analysis by online nano electrospray ionization tandem mass spectrometry. In this
      technique, a titanium dioxide (TiO2)-packed pipette tip is used as a
      phosphopeptide trap that acts as an offline first-dimension separation step in a
      two-dimensional chromatography system. This is followed by online nano reversed
      phase high-performance liquid chromatography. Here, we present suitable methods
      for enrichment, optimized separately for each step: sample loading, washing and
      elution from the TiO2-filled tips. To increase the trapping selectivity of the
      TiO2 column, we used the sodium salt of 1-octanesulfonic acid combined with 2,5
      dihydroxybenzoic acid as ion-pairing agents and displacers for acidic peptides.
      These agents also improve the binding of phosphorylated peptides and block the
      binding of non-phosphorylated ones. This enrichment procedure takes 30 min,
      followed by a 100-min HPLC program, including washing and an elution gradient.

PMID- 17545996
TI  - Metabolism, cytoskeleton and cellular signalling in the grip of protein Nepsilon 
      and O-acetylation.
AB  - Acetylation of the epsilon-amino group of lysine residues (N(epsilon)
      acetylation) is a reversible post-translational modification with the potential
      to rival phosphorylation. In addition to histones and many transcription factors
      such as p53, regulators of DNA repair, replication and recombination are subject
      to N(epsilon)-acetylation. This modification is also important for governing the
      activities of various enzymes, including histone acetyltransferases, histone
      deacetylases, bacterial and mammalian acetyl-CoA synthases, kinases,
      phosphatases, the ubiquitin ligase murine double minute 2 and the chaperonin heat
      shock protein 90. Furthermore, lysine acetylation occurs in cellular structure
      proteins such as alpha-tubulin, actin, cortactin and p120 catenin. Strikingly,
      the Yersinia outer protein YopJ promotes O-acetylation of crucial serine and
      threonine residues that are required for activation of the MAPK/ERK kinase and
      IkappaB kinase families, which precludes their phosphorylation and blocks signal
      transduction. Thus, N(epsilon)- and O-acetylation are becoming recognized as two
      prominent mechanisms for regulating protein functions in diverse organisms.

PMID- 17545999
TI  - Identification and insertion of 3-carbon bridges in protein disulfide bonds: a
      computational approach.
AB  - More than 42,000 3D structures of proteins are available on the Internet. We have
      shown that the chemical insertion of a 3-carbon bridge across the native
      disulfide bond of a protein or peptide can enable the site-specific conjugation
      of PEG to the protein without a loss of its structure or function. For success,
      it is necessary to select an appropriate and accessible disulfide bond in the
      protein for this chemical modification. We describe how to use public protein
      databases and molecular modeling programs to select a protein rationally and to
      identify the optimum disulfide bond for experimental studies. Our computational
      approach can substantially reduce the time required for the laboratory-based
      chemical modification. Identification of solvent-accessible disulfides using
      published structural information takes approximately 2 h. Predicting the
      structural effects of the disulfide-based modification can take 3 weeks.

PMID- 17546000
TI  - Cytokinesis-block micronucleus cytome assay.
AB  - The cytokinesis-block micronucleus cytome assay is a comprehensive system for
      measuring DNA damage, cytostasis and cytotoxicity. DNA damage events are scored
      specifically in once-divided binucleated (BN) cells and include (a) micronuclei
      (MNi), a biomarker of chromosome breakage and/or whole chromosome loss, (b)
      nucleoplasmic bridges (NPBs), a biomarker of DNA misrepair and/or telomere end
      fusions, and (c) nuclear buds (NBUDs), a biomarker of elimination of amplified
      DNA and/or DNA repair complexes. Cytostatic effects are measured via the
      proportion of mono-, bi- and multinucleated cells and cytotoxicity via necrotic
      and/or apoptotic cell ratios. Further information regarding mechanisms leading to
      MNi, NPBs and NBUDs formation is obtained using centromere and/or telomere
      probes. The assay is being applied successfully for biomonitoring of in vivo
      genotoxin exposure, in vitro genotoxicity testing and in diverse research fields
      such as nutrigenomics and pharmacogenomics as well as a predictor of normal
      tissue and tumor radiation sensitivity and cancer risk. The procedure can take up
      to 5 days to complete.

PMID- 17546001
TI  - Cis-regulatory hairpin-shaped mRNA encoding a reporter protein: catalytic sensing
      of nucleic acid sequence at single nucleotide resolution.
AB  - DNA sensing at a single nucleotide resolution is achieved using a hairpin-shaped,
      unmodified (unlabeled) RNA probe or the precursor double-stranded DNA (dsDNA) in
      a prokaryotic cell-free translation medium. The molecular-beacon-like probe
      consists of a loop region that is complementary to the target sequence and a stem
      composed of a ribosome-binding site (RBS) and its docking domain; the RBS is
      followed by the gene for a reporter protein such as luciferase or beta
      galactosidase. Target binding at the loop opens the hairpin to make RBS
      accessible by the ribosome to start translation of the reporter protein. This
      sensing system is signal amplifying by virtue of catalytic DNA-to-RNA
      transcription when using a dsDNA probe, catalytic RNA-to-protein translation,
      catalytic signal transduction by the enzymatic reaction of the translated
      reporter protein and, in the presence of RNase H, catalytic or even irreversible
      translation-activation of the target-probe heteroduplex. Preparation of a probe
      takes 1-3 d and gene sensing using the probe takes 1-3 h.

PMID- 17546002
TI  - In vivo imaging of vesicle motion and release at the Drosophila neuromuscular
      junction.
AB  - Recently, it has become possible to directly detect changes in neuropeptide
      vesicle dynamics in nerve terminals in vivo and to measure the release of
      neuropeptides induced experimentally or evoked by normal behavior. These results
      were obtained with the use of transgenic fruit flies that express a neuropeptide
      tagged with green fluorescent protein. Here, we describe how vesicle movement and
      neuropeptide release can be studied in the larval Drosophila neuromuscular
      junction using fluorescence microscopy. Analysis methods are described for
      quantifying movement based on time lapse and fluorescence recovery after
      photobleaching data. Specific approaches that can be applied to nerve terminals
      include single particle tracking, correlation and Fourier analysis. Utilization
      of these methods led to the first detection of vesicle mobilization in nerve
      terminals and the discoveries of activity-dependent capture of transiting
      vesicles and post-tetanic potentiation of neuropeptide release. Overall, this
      protocol can be carried out in an hour with ready Drosophila.

PMID- 17546003
TI  - Split-intein mediated circular ligation used in the synthesis of cyclic peptide
      libraries in E. coli.
AB  - Recent advances in chemical biology and the advantages presented by in vivo
      screening have highlighted the need for a robust and flexible biologically
      synthesized small-molecule library. Herein we describe a method for the
      biosynthesis of cyclic peptide libraries of up to 10(8) members in Escherichia
      coli using split-intein circular ligation of peptides and proteins (SICLOPPS).
      The method utilizes split-intein chemistry to cyclize randomized peptide
      sequences. The cyclic peptide library can potentially be of any size and the
      peptide itself may contain unlimited random residues. However, the library size
      is limited by the transformation efficiency of E. coli and random residues are
      generally limited to five, but additional amino acids can be used in the cyclic
      peptide backbone, varying the structure and ring size of the cyclic peptide.
      SICLOPPS libraries have been combined with a bacterial reverse two-hybrid system
      in our labs and used in the identification of inhibitors of several protein
      protein interactions. This protocol is expected to take around 3-4 weeks to
      implement.

PMID- 17546004
TI  - Development and optimization of high-throughput in vitro protein phosphatase
      screening assays.
AB  - We describe here detailed protocols to design, optimize and validate in vitro
      phosphatase assays that we have utilized to conduct high-throughput screens for
      inhibitors of dual-specificity phosphatases: CDC25B, mitogen-activated protein
      kinase phosphatase (MKP)-1 and MKP-3. We provide details of the critical steps
      that are needed to effectively miniaturize the assay into a 384-well, high
      throughput format that is both reproducible and cost effective. In vitro
      phosphatase assays that are optimized according to these protocols should satisfy
      the assay performance criteria required for a robust high-throughput assay with Z
      factors >0.5, and with low intra-plate, inter-plate and day-to-day variability
      (CV <20%). Assuming the availability of sufficient active phosphatase enzyme and
      access to appropriate liquid handling automation and detection instruments, a
      single investigator should be able to develop a 384-well format high-throughput
      assay in a period of 3-4 weeks.

PMID- 17546005
TI  - Tandem affinity purification of functional TAP-tagged proteins from human cells.
AB  - Tandem affinity purification (TAP) is a generic two-step affinity purification
      protocol for isolation of TAP-tagged proteins together with associated proteins.
      We used bacterial artificial chromosome to heterologously express TAP-tagged
      murine Sgo1 protein in human HeLa cells. This allowed us to test the
      functionality of the Sgo1-TAP protein by RNA interference-mediated depletion of
      the endogenous human Sgo1. Here, we present an optimized protocol for
      purification of TAP-tagged Sgo1 protein as well as KIAA1387 from HeLa cells with
      detailed instructions. The purification protocol can be completed in 1 day and it
      should be applicable to other proteins.

PMID- 17546006
TI  - Bioconjugated quantum dots for multiplexed and quantitative immunohistochemistry.
AB  - Bioconjugated quantum dots (QDs) provide a new class of biological labels for
      evaluating biomolecular signatures (biomarkers) on intact cells and tissue
      specimens. In particular, the use of multicolor QD probes in immunohistochemistry
      is considered one of the most important and clinically relevant applications. At
      present, however, clinical applications of QD-based immunohistochemistry have
      achieved only limited success. A major bottleneck is the lack of robust protocols
      to define the key parameters and steps. Here, we describe our recent experience,
      preliminary results and detailed protocols for QD-antibody conjugation, tissue
      specimen preparation, multicolor QD staining, image processing and biomarker
      quantification. The results demonstrate that bioconjugated QDs can be used for
      multiplexed profiling of molecular biomarkers, and ultimately for correlation
      with disease progression and response to therapy. In general, QD bioconjugation
      is completed within 1 day, and multiplexed molecular profiling takes 1-3 days
      depending on the number of biomarkers and QD probes used.

PMID- 17546007
TI  - Immobilization of enzymes on heterofunctional epoxy supports.
AB  - Immobilization of enzymes and proteins on activated supports permits the
      simplification of the reactor design and may be used to improve some enzyme
      properties. In this sense, supports containing epoxy groups seem to be useful to
      generate very intense multipoint covalent attachment with different nucleophiles
      placed on the surface of enzyme molecules (e.g., amino, thiol, hydroxyl groups).
      However, the intermolecular reaction between epoxy groups and soluble enzymes is
      extremely slow. To solve this problem, we have designed "tailor-made"
      heterofunctional epoxy supports. Using these, immobilization of enzymes is
      performed via a two-step process: (i) an initial physical or chemical
      intermolecular interaction of the enzyme surface with the new functional groups
      introduced on the support surface and (ii) a subsequent intense intramolecular
      multipoint covalent reaction between the nucleophiles of the already immobilized
      enzyme and the epoxy groups of the supports. The first immobilization may involve
      different enzyme regions, which will be further rigidified by multipoint covalent
      attachment. The design of some heterofunctional epoxy supports and the
      performance of the immobilization protocols are described here. The whole
      protocol to have an immobilized and stabilized enzyme could take from 3 days to 1
      week.

PMID- 17546008
TI  - Generation of a defined and uniform population of CNS progenitors and neurons
      from mouse embryonic stem cells.
AB  - A detailed protocol is described allowing the generation of essentially pure
      populations of glutamatergic neurons from mouse embryonic stem (ES) cells. It is
      based on the culture of ES cells that are kept undifferentiated by repeated
      splitting and subsequently amplified as non-adherent cell aggregates. Treatment
      with retinoic acid causes these ES cells to essentially become neural progenitors
      with the characteristics of Pax6-positive radial glial cells. As they do in vivo,
      these progenitors differentiate in glutamatergic pyramidal neurons that form
      functional synaptic contacts and can be kept in culture for long periods of time.
      This protocol does not require the use of ES lines expressing resistance or
      fluorescent markers and can thus be applied in principle to any wild-type or
      mutant ES line of interest. At least 2 weeks are required from starting ES cell
      culture until plating progenitors and differentiating neurons establish synaptic
      transmission within about 10 days.

PMID- 17546009
TI  - Isolation and culture of rat and mouse oligodendrocyte precursor cells.
AB  - The ability to isolate oligodendroglial precursor cells (OPCs) provides a
      powerful means to characterize their differentiation, properties and potential
      for myelin repair. Although much knowledge is available for isolation of OPCs
      from the rat central nervous system, preparation and maintenance of mouse OPCs
      has been until recently a challenge owing to difficulties in obtaining a
      sufficient quantity of purified OPCs. Here, we describe protocols to prepare
      highly enriched rat OPCs and nearly homogenous mouse OPCs. The mouse method
      generates predominantly OPCs from cortical neural progenitor cells as clonal
      aggregates called "oligospheres" by taking advantage of molecular genetic tools.
      Isolated OPCs can be further differentiated into oligodendrocytes. Collectively,
      we describe simple and efficient methods for the preparation and in vitro
      maintenance of enriched OPCs from rats and mice. Isolation and culture of a
      large, homogenous population of rodent OPCs should significantly facilitate
      studies on OPC lineage progression and their utility in myelin repair after
      injury.

PMID- 17546010
TI  - Synthesis of oligo-RNAs with photocaged adenosine 2'-hydroxyls.
AB  - This protocol describes a general method for the preparation of RNAs in which the
      reactivity or hydrogen-bonding properties of the molecule are modified in a
      photoreversible fashion by use of a caging strategy. A single caged adenosine,
      modified at the 2' position as a nitro-benzyl ether, can be incorporated into
      short RNAs by chemical synthesis or into long RNAs by a combination of chemical
      and enzymatic synthesis. The modified RNAs can be uncaged by photolysis under a
      variety of conditions including the use of a laser or xenon lamp, and the course
      of this uncaging reaction may be readily followed by HPLC or thin-layer
      chromatography.

PMID- 17546011
TI  - A protocol for isolating Xenopus oocyte nuclear envelope for visualization and
      characterization by scanning electron microscopy (SEM) or transmission electron
      microscopy (TEM).
AB  - This protocol details methods for the isolation of oocyte nuclear envelopes (NEs)
      from the African clawed toad Xenopus laevis, immunogold labeling of component
      proteins and subsequent visualization by field-emission scanning electron
      microscopy (FESEM) and transmission electron microscopy (TEM). This procedure
      involves the initial removal of the ovaries from mature female X. laevis, the
      dissection of individual oocytes, then the manual isolation of the giant nucleus
      and subsequent preparation for high-resolution visualization. Unlike light
      microscopy, and its derivative technologies, electron microscopy enables 3-5 nm
      resolution of nuclear structures, thereby giving unrivalled opportunities for
      investigation and immunological characterization in situ of nuclear structures
      and their structural associations. There are a number of stages where samples can
      be stored, although we recommend that this protocol take no longer than 2 d.
      Samples processed for FESEM can be stored for weeks under vacuum, allowing
      considerable time for image acquisition.

PMID- 17546012
TI  - Generation of cell-free extracts of Xenopus eggs and demembranated sperm
      chromatin for the assembly and isolation of in vitro-formed nuclei for Western
      blotting and scanning electron microscopy (SEM).
AB  - This protocol details methods for the generation of cell-free extracts and DNA
      templates from the eggs and sperm chromatin, respectively, of the clawed toad
      Xenopus laevis. We have used this system with scanning electron microscopy (SEM),
      as detailed herein, to analyze the biochemical requirements and structural
      pathways for the biogenesis of eukaryotic nuclear envelopes (NEs) and nuclear
      pore complexes (NPCs). This protocol requires access to female frogs, which are
      induced to lay eggs, and a male frog, which is killed for preparation of the
      sperm chromatin. Egg extracts should be prepared in 1 d and can be stored for
      many months at -80 degrees C. Demembranated sperm chromatin should take only
      approximately 2-3 h to prepare and can be stored at -80 degrees C almost
      indefinitely. The time required for assembly of structurally and functionally
      competent nuclei in vitro depends largely on the quality of the cell-free
      extracts and, therefore, must be determined for each extract preparation.

PMID- 17546013
TI  - Visualization of the nucleus and nuclear envelope in situ by SEM in tissue
      culture cells.
AB  - Our previous work characterizing the biogenesis and structural integrity of the
      nuclear envelope and nuclear pore complexes (NPCs) has been based on amphibian
      material but has recently progressed into the analysis of tissue-culture cells.
      This protocol describes methods for the high resolution visualization, by field
      emission scanning electron microscopy (FESEM), of the nucleus and associated
      structures in tissue culture cells. Imaging by fluorescence light microscopy
      shows general nuclear and NPC information at a resolution of approximately 200
      nm, in contrast to the 3-5 nm resolution provided by FESEM or transmission
      electron microscopy (TEM), which generates detail at the macromolecular level.
      The protocols described here are applicable to all tissue culture cell lines
      tested to date (HeLa, A6, DLD, XTC and NIH 3T3). The processed cells can be
      stored long term under vacuum. The protocol can be completed in 5 d, including 3
      d for cell growth, 1 d for processing and 1 d for imaging.

PMID- 17546014
TI  - Imaging mass spectrometry at cellular length scales.
AB  - Imaging mass spectrometry (IMS) allows the direct investigation of both the
      identity and the spatial distribution of the molecular content directly in tissue
      sections, single cells and many other biological surfaces. In this protocol, we
      present the steps required to retrieve the molecular information from tissue
      sections using matrix-enhanced (ME) and metal-assisted (MetA) secondary ion mass
      spectrometry (SIMS) as well as matrix-assisted laser desorption/ionization
      (MALDI) IMS. These techniques require specific sample preparation steps directed
      at optimal signal intensity with minimal redistribution or modification of the
      sample analytes. After careful sample preparation, different IMS methods offer a
      unique discovery tool in, for example, the investigation of (i) drug transport
      and uptake, (ii) biological processing steps and (iii) biomarker distributions.
      To extract the relevant information from the huge datasets produced by IMS, new
      bioinformatics approaches have been developed. The duration of the protocol is
      highly dependent on sample size and technique used, but on average takes
      approximately 5 h.

PMID- 17546015
TI  - Selective proliferation of rat hepatocyte progenitor cells in serum-free culture.
AB  - This protocol details a method of obtaining selectively proliferated hepatocyte
      progenitor cells using hyaluronic acid (HA)-coated dishes and serum-free medium.
      A small hepatocyte (SH) is a hepatocyte progenitor cell of adult livers and has
      many hepatic functions. When the rat SH begins to proliferate, CD44 is
      specifically expressed. To define the purification of SH, CD44 and cytokeratin 8
      are used as marker proteins. The growth of SHs is faster on HA-coated dishes than
      on other extracellular matrix-coated ones. The use of both DMEM/F12 medium and HA
      coated dishes allows the selective proliferation of SHs in culture. The
      purification of SHs is approximately 85% at day 10.

PMID- 17546016
TI  - Pronuclear injection for the production of transgenic mice.
AB  - Transgenic mice have been instrumental in dissecting the role of various neuronal
      proteins under both physiological and pathological conditions. Pronuclear
      injection is the most widely used protocol for the generation of transgenic mice.
      Here, we describe all steps involved from DNA purification to the set up of a
      mouse colony including vasectomy, injection of the DNA into a donor zygote,
      transfer of injected zygotes into recipient foster mice, screening of offspring
      and establishment of transgenic mouse lines. We discuss the use of neuron
      specific promoters to express proteins with a role in Alzheimer disease.
      Transgenic expression of a truncated form of the microtubule-associated protein
      tau (delta tau) is used as an example for the anticipated results.

PMID- 17546017
TI  - Stripe assay to examine axonal guidance and cell migration.
AB  - Stripe assays have been widely employed as in vitro test systems to study the
      responses of growing axons, as well as migrating cells, to established or novel
      guidance molecules. We provide detailed protocols for both the original and the
      modified version of this assay, as they allow the analysis of the 'guidance
      properties' of active components present in crude membrane fractions or as
      purified molecules. Silicon matrices are used to produce striped patterns of
      active molecules on a surface (referred to as 'carpet'), followed by culturing of
      neurons, or any other cell type, on these carpets. After 1-2 days in culture,
      striped outgrowth of extending neurites--indicative of guided migration of cell
      processes--can be observed. We also discuss potential other applications (e.g.,
      in neuronal regeneration and development) and modifications of the assay. The
      preparation of 10-12 carpets takes approximately 4-5 h.

PMID- 17546018
TI  - Site-specific incorporation of fluorotyrosines into the R2 subunit of E. coli
      ribonucleotide reductase by expressed protein ligation.
AB  - Expressed protein ligation (EPL) allows semisynthesis of a target protein with
      site-specific incorporation of probes or unnatural amino acids at its N or C
      termini. Here, we describe the protocol that our lab has developed for
      incorporating fluorotyrosines (F(n)Ys) at residue 356 of the small subunit of
      Escherichia coli ribonucleotide reductase using EPL. In this procedure, the
      majority of the protein (residues 1-353 out of 375) is fused to an intein domain
      and prepared by recombinant expression, yielding the protein in a thioester
      activated, truncated form. The remainder of the protein, a 22-mer peptide, is
      prepared by solid-phase peptide synthesis and contains the F(n)Y at the desired
      position. Ligation of the 22-mer peptide to the thioester-activated R2 and
      subsequent purification yield full-length R2 with the F(n)Y at residue 356. The
      procedure to generate 100 mg quantities of Y356F(n)Y-R2 takes 3-4 months.

PMID- 17546019
TI  - A protocol for rapid generation of recombinant adenoviruses using the AdEasy
      system.
AB  - Recombinant adenoviruses provide a versatile system for gene expression studies
      and therapeutic applications. We have developed an approach that simplifies the
      generation and production of such viruses called the AdEasy system. A recombinant
      adenoviral plasmid is generated with a minimum of enzymatic manipulations,
      employing homologous recombination in bacteria rather than in eukaryotic cells.
      After transfection of such plasmids into a mammalian packaging cell line, viral
      production is conveniently followed with the aid of GFP encoded by a gene
      incorporated into the viral backbone. This system has expedited the process of
      generating and testing recombinant adenoviruses for a variety of purposes. In
      this protocol, we describe the practical aspects of using the AdEasy system for
      generating recombinant adenoviruses. The full protocol usually takes 4-5 weeks to
      complete.

PMID- 17546020
TI  - Primary culture of bovine chromaffin cells.
AB  - This protocol describes the primary culture of individual chromaffin cells
      derived by enzymatic digestion from the adrenal medulla of the bovine adrenal
      gland. Since the late 1970s, such cells have provided a useful model system to
      study neurotransmitter biosynthesis, storage and release in the catecholaminergic
      system. The protocol can be divided into three stages: isolation of cells (4-6
      h), determination of viable cell numbers (approximately 30 min) and growth in
      culture (3-7 d). An alternative procedure is to perform studies in a continuous
      chromaffin (pheochromocytoma) cell line, such as PC12, although such transformed
      cells are typically less highly differentiated than primary cells. The bovine
      chromaffin cell procedure should yield approximately 10-20 million cells,
      suitable for several experiments over the subsequent 3-7 d. Typical experiments
      involve transmitter biosynthesis, vesicular storage, exocytotic release, stimulus
      coupling (signal transduction) toward secretion or transcription, or morphology,
      including ultrastructure. The total time, from adrenal gland harvest until
      functional experiments, is typically 4-8 d.

PMID- 17546021
TI  - Biosensor-based assays for PQS, HHQ and related 2-alkyl-4-quinolone quorum
      sensing signal molecules.
AB  - 2-Alkyl-4-quinolones (AHQs) such as 2-heptyl-3-hydroxy-4-quinolone (PQS) and 2
      heptyl-4-quinolone (HHQ) are quorum sensing signal molecules. Here, we describe
      methods for AHQ detection, tentative identification and quantification, which
      employ a lux-based Pseudomonas aeruginosa AHQ biosensor strain. The protocol
      describes both thin-layer chromatography (TLC) and microtiter plate assays, which
      use bioluminescence or the green color of pyocyanin as detection end points.
      Organic solvent extracts of bacterial cells or cell-free culture supernatants are
      chromatographed on TLC plates, which are dried and overlaid with the AHQ
      biosensor. AHQs appear as both luminescent and green spots. For the microtiter
      assay, either spent bacterial culture supernatants or extracts are added to a
      growth medium containing the AHQ biosensor. Light output is proportional to the
      AHQ content of the sample. The assays described take approximately 2 days to
      complete, are simple to perform, do not require sophisticated instrumentation and
      are highly amenable to screening large numbers of bacterial samples. However,
      apart from PQS and HHQ in P. aeruginosa, definitive AHQ identification will
      require additional MS and NMR analyses.

PMID- 17546022
TI  - Affinity purification of plasmid DNA by temperature-triggered precipitation.
AB  - This protocol presents a new method to purify plasmid DNA using temperature
      triggered precipitation. The principle is based on the specific DNA-binding
      affinity of a bacterial metalloregulatory (MerR) protein to its cognate DNA
      sequence and the temperature responsiveness of elastin-like protein (ELP). A
      bifunctional ELP-MerR fusion protein is created to enable the precipitation of
      plasmid DNA, designed to contain the MerR recognition sequence, by a simple
      temperature trigger. The protocol covers all stages of the process from the
      design of ELP-MerR fusion proteins and MerR-binding plasmids, to the isolation of
      plasmid DNA from Escherichia coli cultures after boiling lysis, the subsequent
      temperature-triggered precipitation of plasmid DNA-fusion protein complexes and
      final elution of plasmid DNA by mild heating. This protocol is well suited to
      laboratory research-scale applications, producing plasmid DNA of better purity
      and similar yield as one of the most commonly used laboratory methods, standard
      alkaline lysis (known as the midiprep procedure). The protocol takes
      approximately 30 min to obtain pure plasmid DNA from cell cultures using the
      temperature-triggered precipitation method.

PMID- 17546023
TI  - Collagen-induced arthritis.
AB  - The collagen-induced arthritis (CIA) mouse model is the most commonly studied
      autoimmune model of rheumatoid arthritis. Autoimmune arthritis is induced in this
      model by immunization with an emulsion of complete Freund's adjuvant and type II
      collagen (CII). This protocol describes the steps necessary for acquisition,
      handling and preparation of CII, as well as selection of mouse strains, proper
      immunization technique and evaluation of the arthritis incidence and severity.
      Typically, the first signs of arthritis appear in this model 21-28 days after
      immunization, and identification of the arthritic limbs is not difficult. Using
      the protocol described, the investigator should be able to reproducibly induce a
      high incidence of CIA in various strains of genetically susceptible mice as well
      as learn how to critically evaluate the pathology of the disease. The total time
      for the preparation of reagents and the immunization of ten mice is about 1.5 h.

PMID- 17546024
TI  - Mos1-mediated insertional mutagenesis in Caenorhabditis elegans.
AB  - We describe a protocol for mutating genes in the nematode Caenorhabditis elegans
      using the Mos1 transposon of Drosophila mauritiana. Mutated genes containing a
      Mos1 insertion are molecularly tagged by this heterologous transposable element.
      Mos1 insertions can therefore be identified in as little as 3 weeks using only
      basic molecular biology techniques. Mutagenic efficiency of Mos1 is tenfold lower
      than classical chemical mutagens. However, the ease and speed with which
      mutagenic insertions can be mapped compares favorably with the vast amount of
      work involved in classical genetic mapping. Therefore, Mos1 could be the tool of
      choice when screening procedures are efficient. In addition, Mos1 mutagenesis can
      greatly simplify the mapping of mutations that exhibit low penetrance, subtle or
      synthetic phenotypes. The recent development of targeted engineering of C.
      elegans loci carrying Mos1 insertions further increases the attractiveness of
      Mos1-mediated mutagenesis.

PMID- 17546025
TI  - A simple one-pot multicomponent synthesis of an octahedral nanocontainer
      molecule.
AB  - A nearly quantitative 18-component synthesis of a nanocontainer, which is built
      up from six bowl-shaped cavitands that are connected together with 12 -CH=N
      CH2CH2-N=CH- linkers, and its subsequent reduction are described. This
      nanocontainer has an estimated cavity volume of 1,700 A3, large enough to
      encapsulate several smaller guest molecules or a small-sized biomacromolecule.
      Potential uses of this nanocontainer and of water-soluble derivatives are in drug
      delivery, wastewater detoxification, separation technology and as molecular
      reactor for controlled oligomerizations. Typically, the four-step synthesis of
      the cavitand building block and the subsequent multicomponent synthesis of the
      nanocontainer, including its purification, can be accomplished in about 4 weeks.

PMID- 17546026
TI  - Construction of soil environmental DNA cosmid libraries and screening for clones
      that produce biologically active small molecules.
AB  - Culture-independent studies on environmental samples indicate that most bacteria
      are not readily cultured in the laboratory. The small fraction of bacteria that
      have been successfully cultured from environmental samples have been a very
      rewarding source of novel biologically active natural products. The introduction
      of DNA extracted directly from environmental samples into easily cultured
      bacteria and the screening of these large libraries for clones that produce
      biologically active small molecules is one means to access natural products
      encoded by the genomes of previously uncultured bacteria. This protocol provides
      detailed procedures for cloning DNA directly from environmental samples and
      screening these clones for the production of antibacterially active natural
      products. The entire protocol, from soil sample to the identification of
      antibacterially active environmental DNA clones, will take approximately 2 weeks.

PMID- 17546027
TI  - Probabilistic reasoning by neurons.
AB  - Our brains allow us to reason about alternatives and to make choices that are
      likely to pay off. Often there is no one correct answer, but instead one that is
      favoured simply because it is more likely to lead to reward. A variety of
      probabilistic classification tasks probe the covert strategies that humans use to
      decide among alternatives based on evidence that bears only probabilistically on
      outcome. Here we show that rhesus monkeys can also achieve such reasoning. We
      have trained two monkeys to choose between a pair of coloured targets after
      viewing four shapes, shown sequentially, that governed the probability that one
      of the targets would furnish reward. Monkeys learned to combine probabilistic
      information from the shape combinations. Moreover, neurons in the parietal cortex
      reveal the addition and subtraction of probabilistic quantities that underlie
      decision-making on this task.

PMID- 17546028
TI  - RNase H-mediated retrovirus destruction in vivo triggered by
      oligodeoxynucleotides.
AB  - The HIV-1 RNase H can be prematurely activated by oligodeoxynucleotides targeting
      the highly conserved polypurine tract required for second strand DNA synthesis.
      This inhibits retroviral replication in cell-free HIV particles and newly
      infected cells. Here we extend these studies to an in vivo model of retroviral
      replication. Mice that are chronically infected with the spleen focus-forming
      virus and treated with oligodeoxynucleotides that target the polypurine tract,
      exhibit either transient or long-term reductions in plasma virus titer, depending
      on the therapeutic regimen. Treatment prior to, during or shortly after infection
      can delay disease progression, increase survival rates and prevent viral
      infection. This strategy destroys viral RNA template in virus particles in serum
      as well as early retroviral replication intermediates in infected cells. As it
      targets events common to the replication cycle of all retroviruses, this approach
      may be broadly applicable to retroviruses of medical and agricultural importance.

PMID- 17546029
TI  - Mutations in LCA5, encoding the ciliary protein lebercilin, cause Leber
      congenital amaurosis.
AB  - Leber congenital amaurosis (LCA) causes blindness or severe visual impairment at
      or within a few months of birth. Here we show, using homozygosity mapping, that
      the LCA5 gene on chromosome 6q14, which encodes the previously unknown ciliary
      protein lebercilin, is associated with this disease. We detected homozygous
      nonsense and frameshift mutations in LCA5 in five families affected with LCA. In
      a sixth family, the LCA5 transcript was completely absent. LCA5 is expressed
      widely throughout development, although the phenotype in affected individuals is
      limited to the eye. Lebercilin localizes to the connecting cilia of
      photoreceptors and to the microtubules, centrioles and primary cilia of cultured
      mammalian cells. Using tandem affinity purification, we identified 24 proteins
      that link lebercilin to centrosomal and ciliary functions. Members of this
      interactome represent candidate genes for LCA and other ciliopathies. Our
      findings emphasize the emerging role of disrupted ciliary processes in the
      molecular pathogenesis of LCA.

PMID- 17546030
TI  - Mutations in X-linked PORCN, a putative regulator of Wnt signaling, cause focal
      dermal hypoplasia.
AB  - Focal dermal hypoplasia is an X-linked dominant disorder characterized by patchy
      hypoplastic skin and digital, ocular and dental malformations. We used array
      comparative genomic hybridization to identify a 219-kb deletion in Xp11.23 in two
      affected females. We sequenced genes in this region and found heterozygous and
      mosaic mutations in PORCN in other affected females and males, respectively.
      PORCN encodes the human homolog of Drosophila melanogaster porcupine, an
      endoplasmic reticulum protein involved in secretion of Wnt proteins.

PMID- 17546031
TI  - Deficiency of PORCN, a regulator of Wnt signaling, is associated with focal
      dermal hypoplasia.
AB  - Focal dermal hypoplasia (FDH) is an X-linked dominant multisystem birth defect
      affecting tissues of ectodermal and mesodermal origin. Using a stepwise approach
      of (i) genetic mapping of FDH, (ii) high-resolution comparative genome
      hybridization to seek deletions in candidate chromosome areas and (iii) point
      mutation analysis in candidate genes, we identified PORCN, encoding a putative O
      acyltransferase and potentially crucial for cellular export of Wnt signaling
      proteins, as the gene mutated in FDH. The findings implicate FDH as a
      developmental disorder caused by a deficiency in PORCN.

PMID- 17546032
TI  - Allelic 'choice' governs somatic hypermutation in vivo at the immunoglobulin
      kappa-chain locus.
AB  - Monoallelic demethylation and rearrangement control allelic exclusion of the
      immunoglobulin kappa-chain locus (Igk locus) in B cells. Here, through the
      introduction of pre-rearranged Igk genes into their physiological position, the
      critical rearrangement step was bypassed, thereby generating mice producing B
      cells simultaneously expressing two different immunoglobulin-kappa light chains.
      Such 'double-expressing' B cells still underwent monoallelic demethylation at the
      Igk locus, and the demethylated allele was the 'preferred' substrate for somatic
      hypermutation in each cell. However, methylation itself did not directly inhibit
      the activation-induced cytidine-deaminase reaction in vitro. Thus, it seems that
      the epigenetic mechanisms that initially bring about monoallelic variable
      (diversity)-joining rearrangement continue to be involved in the control of
      antibody diversity at later stages of B cell development.

PMID- 17546033
TI  - Comprehensive epigenetic profiling identifies multiple distal regulatory elements
      directing transcription of the gene encoding interferon-gamma.
AB  - Unlike the well defined T helper type 2 cytokine locus, little is known about the
      regulatory elements that govern the expression of Ifng, which encodes the
      'signature' T helper type 1 cytokine interferon-gamma. Here our evolutionary
      analysis showed that the mouse Ifng locus diverged from the ancestral locus as a
      result of structural rearrangements producing deletion of the neighboring gene
      encoding interleukin 26 and disrupting synteny 57 kilobases upstream of Ifng.
      Proximal to that disruption, we identified by high-resolution mapping many
      regions with CD4+ T cell subset-specific epigenetic modifications. A subset of
      those regions represented enhancers, whereas others blocked the activity of
      upstream enhancers or insulated Ifng from neighboring chromatin. Our findings
      suggest that proper expression of Ifng is maintained through the collective
      action of multiple distal regulatory elements present in a region of about 100
      kilobases flanking Ifng.

PMID- 17546034
TI  - Dynamic changes in histone-methylation 'marks' across the locus encoding
      interferon-gamma during the differentiation of T helper type 2 cells.
AB  - The 'histone-code' hypothesis proposes that cell fate 'decisions' are achieved
      through the creation of stable epigenetic histone 'marks' at gene loci. Here we
      explored the formation of marks of repressive methylation of histone 3 at lysine
      9 (H3-K9) and of H3-K27 at the locus encoding interferon-gamma (Ifng locus)
      during the commitment of naive T cells to the T helper type 1 (TH1) and TH2
      lineages. Methylation of H3-K9 across the Ifng locus was rapidly induced in
      differentiating TH1 and TH2 cells and was sustained in TH1 cells. In contrast,
      TH2 differentiation caused loss of methylation of H3-K9 and gain of methylation
      of H3-K27 by mechanisms dependent on the transcription factors GATA-3 and STAT6.
      Thus, histone-methylation marks at the Ifng locus are highly dynamic, which may
      ensure higher-order transcriptional regulation during early lineage commitment.

PMID- 17546035
TI  - Magnetic effects at the interface between non-magnetic oxides.
AB  - The electronic reconstruction at the interface between two insulating oxides can
      give rise to a highly conductive interface. Here we show how, in analogy to this
      remarkable interface-induced conductivity, magnetism can be induced at the
      interface between the otherwise non-magnetic insulating perovskites SrTiO3 and
      LaAlO3. A large negative magnetoresistance of the interface is found, together
      with a logarithmic temperature dependence of the sheet resistance. At low
      temperatures, the sheet resistance reveals magnetic hysteresis. Magnetic ordering
      is a key issue in solid-state science and its underlying mechanisms are still the
      subject of intense research. In particular, the interplay between localized
      magnetic moments and the spin of itinerant conduction electrons in a solid gives
      rise to intriguing many-body effects such as Ruderman-Kittel-Kasuya-Yosida
      interactions, the Kondo effect and carrier-induced ferromagnetism in diluted
      magnetic semiconductors. The conducting oxide interface now provides a versatile
      system to induce and manipulate magnetic moments in otherwise non-magnetic
      materials.

PMID- 17546036
TI  - The self-organizing properties of squid reflectin protein.
AB  - Reflectins, a recently identified protein family that is enriched in aromatic and
      sulphur-containing amino acids, are used by certain cephalopods to manage and
      manipulate incident light in their environment. These proteins are the
      predominant constituent of nanoscaled photonic structures that function in static
      and adaptive colouration, extending visual performance and intra-species
      communication. Our investigation into recombinantly expressed reflectin has
      revealed unanticipated self-assembling and behavioural properties, and we
      demonstrate that reflectin can be easily processed into thin films, photonic
      grating structures and fibres. Our findings represent a key step in our
      understanding of the property-function relationships of this unique family of
      reflective proteins.

PMID- 17546037
TI  - Nucleic acid and protein mass mapping by live-cell deep-ultraviolet microscopy.
AB  - We developed a deep-ultraviolet (UV) microscope capable of imaging cell mitosis
      and motility at 280 nm for 45 min with minimal UV-induced toxicity, and for 6 h
      before the onset of visible cell death in cultured human and mouse cells.
      Combined with computational methods that convert the intensity of each pixel into
      an estimate of mass, deep-UV microscopy images generate maps of nucleic acid
      mass, protein mass and fluorescence yield in unlabeled cells.

PMID- 17546038
TI  - Mast cells promote atherosclerosis by releasing proinflammatory cytokines.
AB  - Mast cells contribute importantly to allergic and innate immune responses by
      releasing various preformed and newly synthesized mediators. Previous studies
      have shown mast cell accumulation in human atherosclerotic lesions. This report
      establishes the direct participation of mast cells in atherogenesis in low
      density lipoprotein receptor-deficient (Ldlr(-/-)) mice. Atheromata from compound
      mutant Ldlr(-/-) Kit(W-sh)(/W-sh) mice showed decreased lesion size, lipid
      deposition, T-cell and macrophage numbers, cell proliferation and apoptosis, but
      increased collagen content and fibrous cap development. In vivo, adoptive
      transfer of syngeneic wild-type or tumor necrosis factor (TNF)-alpha-deficient
      mast cells restored atherogenesis to Ldlr(-/-)Kit(W-sh/W-sh) mice. Notably,
      neither interleukin (IL)-6- nor interferon (IFN)-gamma-deficient mast cells did
      so, indicating that the inhibition of atherogenesis in Ldlr(-/-)Kit(W-sh/W-sh)
      mice resulted from the absence of mast cells and mast cell-derived IL-6 and IFN
      gamma. Compared with wild-type or TNF-alpha-deficient mast cells, those lacking
      IL-6 or IFN-gamma did not induce expression of proatherogenic cysteine proteinase
      cathepsins from vascular cells in vitro or affect cathepsin and matrix
      metalloproteinase activities in atherosclerotic lesions, implying that mast cell
      derived IL-6 and IFN-gamma promote atherogenesis by augmenting the expression of
      matrix-degrading proteases. These observations establish direct participation of
      mast cells and mast cell-derived IL-6 and IFN-gamma in mouse atherogenesis and
      provide new mechanistic insight into the pathogenesis of this common disease.

PMID- 17546039
TI  - Extension of Drosophila melanogaster life span with a GPCR peptide inhibitor.
AB  - G protein-coupled receptors (GPCRs) mediate signaling from extracellular ligands
      to intracellular signal transduction proteins. Methuselah (Mth) is a class B
      (secretin-like) GPCR, a family typified by their large, ligand-binding, N
      terminal extracellular domains. Downregulation of mth increases the life span of
      Drosophila melanogaster; inhibitors of Mth signaling should therefore enhance
      longevity. We used mRNA display selection to identify high-affinity (K(d) = 15 to
      30 nM) peptide ligands that bind to the N-terminal ectodomain of Mth. The
      selected peptides are potent antagonists of Mth signaling, and structural studies
      suggest that they perturb the interface between the Mth ecto- and transmembrane
      domains. Flies constitutively expressing a Mth antagonist peptide have a robust
      life span extension, which suggests that the peptides inhibit Mth signaling in
      vivo. Our work thus provides new life span-extending ligands for a metazoan and a
      general approach for the design of modulators of this important class of GPCRs.

PMID- 17546040
TI  - Molecular basis for the functional interaction of dynein light chain with the
      nuclear-pore complex.
AB  - Nucleocytoplasmic transport occurs through nuclear pore complexes (NPCs) embedded
      in the nuclear envelope. Here, we discovered an unexpected role for yeast dynein
      light chain (Dyn2) in the NPC. Dyn2 is a previously undescribed nucleoporin that
      functions as molecular glue to dimerize and stabilize the Nup82-Nsp1-Nup159
      complex, a module of the cytoplasmic pore filaments. Biochemical analyses showed
      that Dyn2 binds to a linear motif (termed DID(Nup159)) inserted between the Phe
      Gly repeat and coiled-coil domain of Nup159. Electron microscopy revealed that
      the reconstituted Dyn2-DID(Nup159) complex forms a rigid rod-like structure, in
      which five Dyn2 homodimers align like 'pearls on a string' between two extented
      DID(Nup159) strands. These findings imply that the rigid 20 nm long Dyn2
      DID(Nup159) filament projects the Nup159 Phe-Gly repeats from the Nup82 module.
      Thus, it is possible that dynein light chain plays a role in organizing natively
      unfolded Phe-Gly repeats within the NPC scaffold to facilitate nucleocytoplasmic
      transport.

PMID- 17546041
TI  - Assessment of MLH1 promoter methylation in relation to gene expression requires
      specific analysis.
AB  - About 15% of colorectal cancers are called MSI because they demonstrate
      microsatellite instability. In most sporadic MSI cases, the DNA mismatch repair
      (MMR) defect is due to methylation of the MLH1 promoter. In hereditary MSI cases,
      it is the consequence of germline mutations of one of the MMR genes. We analysed
      the MLH1 promoter for methylation using the methylation-specific PCR technique.
      With a previously described and widely used primer set, a number of samples with
      an intact MMR system were found to have methylated MLH1 promoter, a finding
      normally associated with lack of MLH1 expression. Another primer set, specific
      for a more proximal region of the promoter, gave results that correlated more
      closely with loss of MLH1 expression. We then conducted a survey of the
      literature on the subject, and a total of 161 articles were examined. Although it
      was shown as early as 1999 that absence of MLH1 expression correlated with
      methylation of the proximal but not distal regions of the MLH1 promoter, 60% of
      published studies analysed nonspecific regions. Our findings suggest that these
      studies are likely to have wrongly estimated the association between methylation
      of the MLH1 gene and the lack of its protein expression.

PMID- 17546042
TI  - Role of CEACAM1 isoforms in an in vivo model of mammary morphogenesis: mutational
      analysis of the cytoplasmic domain of CEACAM1-4S reveals key residues involved in
      lumen formation.
AB  - CEACAM1 (carcinoembryonic antigen-related cell adhesion molecule 1) is a type I
      transmembrane glycoprotein expressed in epithelial cells with three or four
      extracellular domains (ECDs) and either long or short cytoplasmic domain
      isoforms. We have previously shown that the four extracellular domains, short
      cytoplasmic domain isoform, CEACAM1-4S, plays an essential role in lumen
      formation in an in vitro model of mammary morphogenesis. In this study, we
      transfected MCF-7 cells with either the long or short cytoplasmic domain isoforms
      of CEACAM1, and grew the cells in humanized mammary mouse fat pads in NOD/SCID
      mice. In this in vivo model, only the long cytoplasmic domain isoform, CEACAM1
      4L, formed glands with lumen. On the basis of other studies that revealed
      phosphorylation of key Thr and Ser residues in the short cytoplasmic domain, we
      introduced phosphorylation mimic (for example, Thr or Ser to Asp) or null (Thr or
      Ser to Ala) mutations into the cytoplasmic domain of CEACAM1-4S and tested them
      in the in vivo model. Mutation of either Thr or Ser to Asp or the double mutant
      Thr+Ser to Asp, but not the null mutants, induced gland formation with a central
      lumen-containing apoptotic cells. Moreover, the phosphorylation mimic mutants of
      CEACAM1-4S induced downregulation of beta1-integrin, overexpression of beta2
      integrin, inhibited phosphorylation of focal adhesion kinase (pTyr-397) and
      resulted in myofibroblast differentiation as characterized by expression of
      vimentin, alpha-smooth muscle actin and beta2-integrin, as well as the production
      of abundant extracellular matrix.

PMID- 17546043
TI  - TrkC binds to the type II TGF-beta receptor to suppress TGF-beta signaling.
AB  - Growing evidence suggests that overexpression of TrkC, a member of the Trk family
      of neurotrophin receptors, could drive tumorigenesis, invasion and metastatic
      capability in cancer cells. However, relatively little is known about the
      mechanism of TrkC-mediated oncogenesis. The TrkC gene is a partner of the Tel
      TrkC (ETV6-NTRK3) chimeric tyrosine kinase, a potent oncoprotein expressed in
      tumors derived from multiple cell lineages. Recently, we have shown that ETV6
      NTRK3 suppresses transforming growth factor-beta (TGF-beta) signaling by directly
      binding to the type II TGF-beta receptor (TbetaRII). Here, we report that
      expression of TrkC also suppresses TGF-beta-induced Smad2/3 phosphorylation and
      transcriptional activation. Silencing TrkC expression by small interfering RNA in
      the highly metastatic 4T1 mammary tumor cell line expressing endogenous TrkC
      significantly enhanced TGF-beta-induced Smad2/3 phosphorylation and restored TGF
      beta growth inhibitory activity. In contrast, expression of TrkC in 67NR cells,
      in which TrkC is not expressed, suppressed TGF-beta transcriptional activation.
      Moreover, we show that TrkC directly binds to the TbetaRII, thereby preventing it
      from interacting with the type I TGF-beta receptor (TbetaRI). These results
      indicate that TrkC is an inhibitor of TGF-beta tumor suppressor activity.

PMID- 17546044
TI  - PLDLS-dependent interaction of E1A with CtBP: regulation of CtBP nuclear
      localization and transcriptional functions.
AB  - C-terminal binding proteins (CtBPs) are cellular corepressors that are targeted
      by adenovirus E1A. A conserved motif of E1A (PLDLS) interacts with an N-terminal
      hydrophobic cleft of CtBPs. Many cellular cofactors also interact with CtBPs
      through PLDLS-like motifs. E1A interaction with CtBP2 changed the composition of
      the CtBP2 protein complex and enhanced CtBP2 acetylation. We have identified a
      mutant of CtBP2 (M48A) that fails to interact with cellular cofactors while
      interacting normally with E1A. Other cleft mutations in CtBP2 affected
      interaction of both cellular cofactors and E1A. The M48A mutant did not repress
      the cellular E-cadherin promoter but inhibited transactivation mediated by the
      E1A N-terminal region through interaction with the E1A PLDLS motif. In vitro, E1A
      enhanced CtBP2 acetylation by p300 via a mechanism involving dissociation of
      acetylated CtBP2 from p300. E1A enhanced nuclear localization of CtBP1 as well as
      a cytoplasmically localized acetylation-deficient mutant of CtBP2 (3KR-CtBP2)
      through PLDLS-dependent interaction. Chromatin immunoprecipitation assays
      revealed presence of CtBP2 on E-cadherin and c-fos promoters. While E1A did not
      significantly alter targeting of CtBP2 to the E-cadherin and c-fos promoters, it
      dramatically enhanced promoter targeting of 3KR-CtBP2. Our results raise a
      possibility that E1A may gain access to cellular promoters through PLDLS
      dependent interaction with CtBPs.

PMID- 17546045
TI  - Repression of Dmp1 and Arf transcription by anthracyclins: critical roles of the
      NF-kappaB subunit p65.
AB  - Both genotoxic and oncogenic stress activates the nuclear factor-kappa B (NF
      kappaB) and p53 proteins; however, the p53 activity is antagonized by NF-kappaB
      signaling. Dmp1 is a Myb-like transcription factor that activates the Arf-p53
      pathway. The Dmp1 promoter was activated by a classical NF-kappaB activator tumor
      necrosis factor alpha, but repressed by treatment of cells with non-classical NF
      kappaB activators, anthracyclins and UV-C. p65 and other subsets of NF-kappaB
      proteins were bound to the Dmp1 promoter following anthracyclin/UV-C treatment of
      rodent fibroblasts. This resulted in the downregulation of Dmp1 mRNA and protein.
      Repression of the Dmp1 transcription by anthracyclins depended on the unique NF
      kappaB site on the promoter. Downregulation of p65 significantly attenuated the
      repression of the Dmp1 promoter by anthracyclins/UV-C. The amount of Dmp1 bound
      to the Arf promoter decreased significantly upon anthracyclin treatment; this, in
      turn, downregulated the Arf levels. Repression of the Arf promoter by p65 or
      anthracyclins depended on Dmp1, which was significantly attenuated in Dmp1(-/-)
      cells. Both Dmp1(-/-)and Arf(-/-)cells showed resistance to anthracyclin-induced
      cell death compared to wild-type cells; non-immortalized p65-knockdown cells were
      much more sensitive. Thus, the Dmp1-Arf pathway is repressed by p65 in response
      to genotoxic stress, which implicates a novel mechanism of p53 inactivation by NF
      kappaB.

PMID- 17546046
TI  - Expression of the RNA-binding protein IMP1 correlates with poor prognosis in
      ovarian carcinoma.
AB  - The IMP (IGFII mRNA-binding protein) family comprises a group of three RNA
      binding proteins involved in the regulation of cytoplasmic mRNA-fate. Recent
      studies identified IMP proteins as oncofetal factors in various neoplasias, but
      knowledge of a potential role in ovarian carcinomas is still lacking. The
      immunohistochemical analysis of 107 ovarian carcinomas, 30 serous borderline
      tumors of the ovary and five normal ovaries revealed de novo synthesis of IMP1 in
      69% of ovarian carcinomas. Elevated IMP1 expression was observed preferentially
      in high-grade and high-stage cases and was a significant prognostic indicator for
      reduced recurrence-free and overall survival. Phenotypic studies in ovarian
      carcinoma-derived ES-2 cells demonstrated that IMP1 knockdown affects
      proliferation and cell survival. Reduced proliferation was associated with
      decreased c-myc mRNA half-life, suggesting IMP1 as an oncogenic factor that is
      involved in promoting elevated proliferation by stabilizing the c-myc mRNA in
      ovarian carcinoma cells.

PMID- 17546047
TI  - Regulation of mitochondrial Smac/DIABLO-selective release by survivin.
AB  - The intrinsic apoptotic pathway is characterized by the release of several
      mitochondrial intermembrane proteins into the cytosol of dying cells. It is
      unclear whether the release of these proteins follows a common or specific
      pathway. In the present report we show that survivin and, to a lesser extent, the
      survivin splice variant survivin DeltaEx3 regulate the specific liberation of
      second mitochondria-derived activator of caspase/direct IAP binding protein with
      low pI (Smac/DIABLO), an inhibitor of apoptosis proteins binding protein, during
      apoptosis induced by etoposide, a DNA damaging agent. This antineoplastic drug
      induced posttranscriptional upregulation of survivin and survivin DeltaEx3. In
      turn, mitochondrial survivin associated with Smac/DIABLO, delaying its release.
      In addition, cytosolic survivin also stabilized the cytosolic levels of released
      Smac/DIABLO. These results provide an explanation for the observed differences in
      the release of mitochondrial intermembrane proteins in various apoptotic models
      and present a new mechanism for the anti-apoptotic effects of survivin in cancer
      cells.

PMID- 17546048
TI  - Epigenetic identification of ADAMTS18 as a novel 16q23.1 tumor suppressor
      frequently silenced in esophageal, nasopharyngeal and multiple other carcinomas.
AB  - Tumor suppressor genes (TSGs) often locate at chromosomal regions with frequent
      deletions in tumors. Loss of 16q23 occurs frequently in multiple tumors,
      indicating the presence of critical TSGs at this locus, such as the well-studied
      WWOX. Herein, we found that ADAMTS18, located next to WWOX, was significantly
      downregulated in multiple carcinoma cell lines. No deletion of ADAMTS18 was
      detected with multiplex differential DNA-PCR or high-resolution 1-Mb array-based
      comparative genomic hybridization (CGH) analysis. Instead, methylation of the
      ADAMTS18 promoter CpG Island was frequently detected with methylation-specific
      PCR and bisulfite genome sequencing in multiple carcinoma cell lines and primary
      carcinomas, but not in any nontumor cell line and normal epithelial tissue. Both
      pharmacological and genetic demethylation dramatically induced the ADAMTS18
      expression, indicating that CpG methylation directly contributes to the tumor
      specific silencing of ADAMTS18. Ectopic ADAMTS18 expression led to significant
      inhibition of both anchorage-dependent and -independent growth of carcinoma cells
      lacking the expression. Thus, through functional epigenetics, we identified
      ADAMTS18 as a novel functional tumor suppressor, being frequently inactivated
      epigenetically in multiple carcinomas.

PMID- 17546049
TI  - KIT oncogenic signaling mechanisms in imatinib-resistant gastrointestinal stromal
      tumor: PI3-kinase/AKT is a crucial survival pathway.
AB  - Most gastrointestinal stromal tumor (GIST) patients respond to KIT inhibition
      with imatinib, yet will eventually exhibit resistance. Imatinib-resistance
      mechanisms are heterogeneous, and little is known about KIT functional roles in
      imatinib-resistant GIST. Biological consequences of biochemical inhibition of
      KIT, phosphatidyl-inositol-3-kinase (PI3-K), PLCgamma, MAPK/ERK kinase/mitogen
      activated protein kinase (MEK/MAPK), mammalian target of rapamycin (mTOR) and JAK
      were determined by immunoblotting for protein activation, and by cell
      proliferation and apoptosis assays in GIST cell lines from imatinib-sensitive
      GIST (GIST882), imatinib-resistant GISTs (GIST430 and GIST48) and KIT-negative
      GIST (GIST62). KIT activation was 3- to 6-fold higher in GIST430 and GIST48 than
      in GIST882, whereas total KIT expression was comparable in these three GIST
      lines. In addition to the higher set point for KIT activation, GIST430 and GIST48
      had intrinsic imatinib resistance. After treatment with 1 muM imatinib, residual
      KIT activation was 6- and 2.8-fold higher in GIST430 and GIST48, respectively,
      compared to GIST882. In all GIST lines, cell growth arrest resulted from PI3-K
      inhibition, and - to a lesser extent - from MEK/MAPK and mTOR inhibition.
      Inhibition of JAK/STAT or PLCgamma did not affect cell proliferation. Similarly,
      only PI3-K inhibition resulted in substantial apoptosis in the imatinib-resistant
      GISTs. We conclude that GIST secondary KIT mutations can be associated with KIT
      hyperactivation and imatinib resistance. Targeting critical downstream signaling
      proteins, such as PI3-K, is a promising therapeutic strategy in imatinib
      resistant GISTs.

PMID- 17546050
TI  - Progesterone enhances branching morphogenesis in the mouse mammary gland by
      increased expression of Msx2.
AB  - Branching morphogenesis within the peripubertal mouse mammary gland is directed
      by progesterone (P). A role for the homeobox-containing transcription factor,
      Msx2, during branching morphogenesis is suggested from its ontogenic expression
      profile and hormonal regulation. Herein, we define the spatio-temporal control of
      Msx2 expression, the regulation of its expression by P and its direct role in
      ductal branching morphogenesis. P induces Msx2 in the presence of estrogen (E)
      both in vitro and in vivo while absence of the P receptor (PR) decreased Msx2
      expression. Stable transfection of PR into mouse mammary epithelial cells
      increased the endogenous expression of Msx2 and their ability to undergo
      branching morphogenesis in vitro. Furthermore, normal mammary cells stably
      transfected with Msx2 demonstrated increased branching morphogenesis in vitro
      while transgenic mice expressing Msx2 in their mammary glands demonstrated
      enhanced lateral branching during early development. The action of P on branching
      morphogenesis appears to involve Bmp2/4. Together, these data demonstrate that P,
      acting through PR-A and the Bmp2/4 pathway, induces Msx2 to enhance ductal
      branching in the mammary glands.

PMID- 17546051
TI  - DNA damage response mediators MDC1 and 53BP1: constitutive activation and
      aberrant loss in breast and lung cancer, but not in testicular germ cell tumours.
AB  - MDC1 and 53BP1 are critical components of the DNA damage response (DDR) machinery
      that protects genome integrity and guards against cancer, yet the tissue
      expression patterns and involvement of these two DDR adaptors/mediators in human
      tumours remain largely unknown. Here we optimized immunohistochemical analyses of
      human 53BP1 and MDC1 proteins in situ and identified their virtually ubiquitous
      expression, both in proliferating and quiescent, differentiated tissues. Focus
      formation by 53BP1 and/or MDC1 in human spermatogenesis and subsets of breast and
      lung carcinomas indicated physiological and 'pathological' activation of the DDR,
      respectively. Furthermore, aberrant reduction or lack of either protein in
      significant proportions of carcinomas supported the candidacy of 53BP1 and MDC1
      for tumour suppressors. Contrary to carcinomas, almost no activation or loss of
      MDC1 or 53BP1 were found among testicular germ-cell tumours (TGCTs), a tumour
      type with unique biology and exceptionally low incidence of p53 mutations. Such
      concomitant presence (in carcinomas) or absence (in TGCTs) of DDR activation and
      DDR aberrations supports the roles of MDC1 and 53BP1 within the ATM/ATR-regulated
      checkpoint network which, when activated, provides an early anti-cancer barrier
      the pressure of which selects for DDR defects such as p53 mutations or loss of
      53BP1/MDC1 during cancer progression.

PMID- 17546052
TI  - C-terminal-binding protein interacting protein binds directly to adenovirus early
      region 1A through its N-terminal region and conserved region 3.
AB  - C-terminal-binding protein interacting protein (CtIP) was first isolated as a
      binding partner of C-terminal-binding protein (CtBP). It is considered to
      contribute to the transcriptional repression and cell cycle regulatory properties
      of the retinoblastoma (Rb) family of proteins and to have a role in the cellular
      response to DNA damage. Here, we have shown that CtIP is a novel target for the
      adenovirus oncoprotein early region 1A (AdE1A). AdE1A associates with CtIP in
      both Ad5E1-transformed cells and Ad5-infected cells and binds directly in
      glutathione-S-transferase pull-down assays. Two binding sites have been mapped on
      Ad5E1A - the N-terminal alpha-helical region (residues 1-30) and conserved region
      3 (CR3) - the transcriptional activation domain. CtIP can bind AdE1A and CtBP
      independently, raising the possibility that ternary complexes exist in Ad
      transformed and -infected cells. Significantly, reduction of CtIP expression with
      small interfering RNAs results in reduction of the ability of a Gal4 DNA-binding
      domain-CR3 construct to transactivate a Gal 4-responsive luciferase reporter and
      this effect is reversed by reduction of CtBP expression. Therefore, in this
      model, CtIP acts as a transcriptional co-activator of AdE1A when dissociated from
      CtBP, through the action of AdE1A. These data are consistent with observations
      that CtIP expression is induced by AdE1A during viral infection and that
      reduction of CtIP expression with RNA interference can retard virus replication.
      In addition, AdE1A causes disruption of the CtIP/Rb complex during viral
      infection by its interaction with CtIP, possibly contributing to transcriptional
      derepression.

PMID- 17546053
TI  - The leukemia-associated cytoplasmic nucleophosmin mutant is an oncogene with
      paradoxical functions: Arf inactivation and induction of cellular senescence.
AB  - Mutations leading to aberrant cytoplasmic localization of Nucleophosmin 1 (NPM1)
      have been recently identified as the most frequent genetic alteration in acute
      myelogenous leukemia. However, the oncogenic potential of this nucleophosmin
      mutant (NPMc+) has never been established, which casts doubt on its role in
      leukemogenesis. By performing classical transformation assays, we find that
      NPMc+, but not wild-type NPM, cooperates specifically with adenovirus E1A to
      transform primary mouse embryonic fibroblasts in soft agar. We demonstrate that
      NPMc+ blocks the p19(Arf) (Arf) induction elicited by E1A. Surprisingly, however,
      we find that NPMc+ induces cellular senescence and that E1A is able to overcome
      this response. We propose a model whereby the NPMc+ pro-senescence activity needs
      to be evaded for oncogenic transformation, even though NPMc+ can concomitantly
      blunt the Arf/p53 pathway. These findings identify for the first time NPMc+ as an
      oncogene and shed new unexpected light on its mechanism of action.

PMID- 17546054
TI  - Roles for negative cell regulator 14-3-3sigma in control of MDM2 activities.
AB  - The 14-3-3sigma, upregulated by p53 in response to DNA damage, can have a
      positive-feedback impact driving p53 activities and is a human cancer epithelial
      marker downregulated in various tumors. However, the precise roles of 14-3-3sigma
      during tumorigenesis are not well characterized. Here, we show that 14-3-3sigma
      is a critical regulator of murine double minute oncogene (MDM2). 14-3-3sigma
      interacts with MDM2 at the RING domain. The C-terminal region of 14-3-3sigma
      binds to MDM2 very efficiently. Importantly, 14-3-3sigma overexpression leads to
      destabilization of MDM2 through enhancing MDM2 self-ubiquitination and
      accelerating turnover rate. Conversely, loss of 14-3-3sigma results in a
      significant increase in MDM2 protein. Moreover, live-cell images indicated that
      14-3-3sigma can affect the location of MDM2 from the nucleus to the cytoplasm,
      and that MDM2-mediated cytoplasmic localization of p53 can be reversed by the
      presence of 14-3-3sigma. Significantly, we further showed that 14-3-3sigma causes
      MDM2 downregulation, thereby stabilizing p53 and inhibiting tumor growth in
      animal tumors. Also, 14-3-3sigma blocks MDM2-mediated retinoblastoma degradation
      and p53 NEDDylation. Our results provide evidence that 14-3-3sigma is a pivotal
      MDM2 regulator involved in blocking a variety of activities of MDM2.

PMID- 17546055
TI  - The reversible epigenetic silencing of BRM: implications for clinical targeted
      therapy.
AB  - The SWI/SNF chromatin-remodeling complex serves as a master switch that directs
      and limits the execution of specific cellular programs, such as differentiation
      and growth control. SWI/SNF function requires one of two paralogous ATPase
      subunits, Brahma (BRM) or BRM-related gene 1 (BRG1), which we previously found
      are lost together in cancer cell lines and primary lung cancers. Although BRG1
      has been found to be mutated in cancer cell lines, the mechanisms underlying BRM
      silencing are not known. To address this question, we sequenced BRM in 10
      BRM/BRG1-deficient cancer cell lines and found that BRM was devoid of abrogating
      mutations. Moreover, histone deacetylase (HDAC) inhibitors restored BRM
      expression in each of these BRG1/BRM-deficient cancer cell lines, indicating that
      epigenetic silencing is a major mechanism underlying the loss of BRM expression.
      Despite their ability to restore BRM expression, these HDAC inhibitors also
      blocked BRM function when present. However, after their removal, we observed that
      BRM expression remained elevated for several days, and during this period, BRM
      activity was detected. We also found that the suppression of BRM occurs in a
      broad range of human tumor types and that loss of one or both BRM alleles
      potentiated tumor development in mice. Thus, BRG1 and BRM are silenced by
      different mechanisms, and it may be possible to clinically target and reexpress
      BRM in a number of tumor types, potentially impacting tumor development.

PMID- 17546056
TI  - Disruption of transforming growth factor-beta signaling through beta-spectrin ELF
      leads to hepatocellular cancer through cyclin D1 activation.
AB  - Transforming growth factor-beta (TGF-beta) signaling members, TGF-beta receptor
      type II (TBRII), Smad2, Smad4 and Smad adaptor, embryonic liver fodrin (ELF), are
      prominent tumor suppressors in gastrointestinal cancers. Here, we show that 40%
      of elf(+/-) mice spontaneously develop hepatocellular cancer (HCC) with markedly
      increased cyclin D1, cyclin-dependent kinase 4 (Cdk4), c-Myc and MDM2 expression.
      Reduced ELF but not TBRII, or Smad4 was observed in 8 of 9 human HCCs (P<0.017).
      ELF and TBRII are also markedly decreased in human HCC cell lines SNU-398 and SNU
      475. Restoration of ELF and TBRII in SNU-398 cells markedly decreases cyclin D1
      as well as hyperphosphorylated-retinoblastoma (hyperphosphorylated-pRb). Thus, we
      show that TGF-beta signaling and Smad adaptor ELF suppress human
      hepatocarcinogenesis, potentially through cyclin D1 deregulation. Loss of ELF
      could serve as a primary event in progression toward a fully transformed
      phenotype and could hold promise for new therapeutic approaches in human HCCs.

PMID- 17546060
TI  - Clinical performance of reinforced glass ionomer restorations placed in UK dental
      practices.
AB  - AIM: To retrospectively evaluate the performance of reinforced glass ionomer
      restorations placed in load-bearing surfaces of posterior teeth in three UK
      general dental practices. METHODS: Inclusion criteria for the participating
      practitioners were that they would be able to find, in their regularly attending
      patients' mouths, a minimum of 30 Fuji IX restorations placed in load-bearing
      cavities in posterior teeth. The three practitioners who agreed to participate
      were given training in the methods of assessment of restorations.
      Presence/absence of the restoration, presence of secondary caries, anatomic form,
      margin adaptation, margin discolouration, surface roughness and colour match were
      recorded. RESULTS: Three general dental practitioners and 169 restorations in 116
      patients were included in the study. Seventy-eight percent of restorations were
      placed in molar teeth, the remainder in premolar teeth, with 67 being Class I and
      102 Class II. The mean age of restorations at examination was 25 months, ranging
      from five months to 56 months. Of the restorations examined, 98% (n = 166) were
      found to be present and intact. No secondary caries was detected clinically.
      Three restorations were found to have fractured. CONCLUSION: Reinforced glass
      ionomer restorations placed in load-bearing situations in patients attending
      three dental practices in the UK were found to be performing satisfactorily at
      two years. Further investigations, of improved rigour, may now be indicated to
      more fully assess the performance of such restorations in the long term.

PMID- 17546066
TI  - The 5S DNA sequences in Hordeum bogdanii and in the H. brevisubulatum complex,
      and the evolution and the geographic dispersal of the diploid Hordeum species
      (Triticeae: Poaceae).
AB  - The molecular diversity of 5S rDNA from the closely related Asiatic diploid
      species, Hordeum bogdanii and the H. brevisubulatum complex has been catalogued
      and analysed. As in previous studies in Hordeum, we found that the sequences are
      constrained in such an manner that unit classes can be defined. The long H1 unit
      class, known to occur in all Eurasian species, was frequently found in these 2
      taxa. In addition, we identified a new unit class, called the short H3 to reflect
      the H genome found in these 2 taxa. Although the 2 taxa are very close
      morphologically, the variation in the long H1 DNA units is constrained to such a
      great degree that, in many cases, the accessions in a unit class from a single
      species are clustered. In H. bogdanii, the majority of the sequences are grouped
      in this manner, whereas in the H. brevisubulatum complex, the tendency to be
      constrained is lower in some but not all subspecies. These results support
      keeping H. brevisubulatum ssp. violaceum and ssp. iranicum as 1 species with the
      long H1 and short H1 unit classes, while retaining ssp. nevskianum and ssp.
      turkestanicum in the H. brevisubulatum complex. We have summarized our work on
      the presence/absence of the 10 unit classes found in all diploid species of
      Hordeum. A phylogenetic analysis, based strictly on the presence/absence of unit
      classes, indicated clearly that all the South American diploids and all the North
      American diploids possess long H2 and long Y2 unit classes and, except for H.
      californicum and H. pusillum, which contain long H1 in addition to the long H2
      and long Y2 classes, are devoid of the long H1 unit class. This suggests that the
      gene gain/loss process from a common ancestor has been concomitant with
      intercontinental dispersal between the Old and the New Worlds.

PMID- 17546067
TI  - New STS molecular markers for assessment of genetic diversity and DNA
      fingerprinting in hop (Humulus lupulus L.).
AB  - Molecular markers have been increasingly used in genetic studies of crop species
      for their applicability in breeding programs. In this work, we report on the
      development of new sequence-tagged site (STS) markers based on sequence
      information from several identified hop (Humulus lupulus L.) genes. We
      demonstrate the usefulness of these STS markers and compare them to SSRs for
      identifying hop genotypes and estimating genetic diversity in a collection of 68
      hop cultivars from around the world. We found 3 individual gene variants (A, B,
      C) of the chs_H1 gene in this collection. The most frequent gene variant, B
      (AJ304877), was not detected in Mt. Hood, Glacier, and Horizon (US) cultivars.
      Gene variant A came from an American germplasm through wild hops. We found length
      polymorphism in intron 1 of the chs2 gene, and 4 different amplified markers were
      detected in PCRs. The chs3 gene was found in only one third of the cultivars.
      None of the variants of the studied CHS genes were found in Humulus japonicus. We
      detected 5 major gene variants of DNA-binding protein in the collection of H.
      lupulus cultivars and 2 others in H. japonicus. We also found 3 individual gene
      variants of an endochitinase gene. The distribution of gene variants did not
      correlate with any resistance. We proved that developed STS markers can be
      successfully used for the analysis of genetic diversity and can substitute and
      supplement SSR markers in hop.

PMID- 17546068
TI  - Genetic mapping of ascochyta blight resistance in chickpea (Cicer arietinum L.)
      using a simple sequence repeat linkage map.
AB  - Ascochyta blight, caused by the fungus Ascochyta rabiei (Pass.) Lab., is one of
      the most devastating diseases of chickpea (Cicer arietinum L.) worldwide.
      Research was conducted to map genetic factors for resistance to ascochyta blight
      using a linkage map constructed with 144 simple sequence repeat markers and 1
      morphological marker (fc, flower colour). Stem cutting was used to vegetatively
      propagate 186 F2 plants derived from a cross between Cicer arietinum L.
      'ICCV96029' and 'CDC Frontier'. A total of 556 cutting-derived plants were
      evaluated for their reaction to ascochyta blight under controlled conditions.
      Disease reaction of the F1 and F2 plants demonstrated that the resistance was
      dominantly inherited. A Fain's test based on the means and variances of the
      ascochyta blight reaction of the F3 families showed that a few genes were
      segregating in the population. Composite interval mapping identified 3 genomic
      regions that were associated with the reaction to ascochyta blight. One
      quantitative trait locus (QTL) on each of LG3, LG4, and LG6 accounted for 13%,
      29%, and 12%, respectively, of the total estimated phenotypic variation for the
      reaction to ascochyta blight. Together, these loci controlled 56% of the total
      estimated phenotypic variation. The QTL on LG4 and LG6 were in common with the
      previously reported QTL for ascochyta blight resistance, whereas the QTL on LG3
      was unique to the current population.

PMID- 17546069
TI  - Identification of molecular markers associated with mite resistance in coconut
      (Cocos nucifera L.).
AB  - Coconut mite (Aceria guerreronis 'Keifer') has become a major threat to Indian
      coconut (Coccos nucifera L.) cultivators and the processing industry. Chemical
      and biological control measures have proved to be costly, ineffective, and
      ecologically undesirable. Planting mite-resistant coconut cultivars is the most
      effective method of preventing yield loss and should form a major component of
      any integrated pest management stratagem. Coconut genotypes, and mite-resistant
      and -susceptible accessions were collected from different parts of South India.
      Thirty-two simple sequence repeat (SSR) and 7 RAPD primers were used for
      molecular analyses. In single-marker analysis, 9 SSR and 4 RAPD markers
      associated with mite resistance were identified. In stepwise multiple regression
      analysis of SSRs, a combination of 6 markers showed 100% association with mite
      infestation. Stepwise multiple regression analysis for RAPD data revealed that a
      combination of 3 markers accounted for 83.86% of mite resistance in the selected
      materials. Combined stepwise multiple regression analysis of RAPD and SSR data
      showed that a combination of 5 markers explained 100% of the association with
      mite resistance in coconut. Markers associated with mite resistance are important
      in coconut breeding programs and will facilitate the selection of mite-resistant
      plants at an early stage as well as mother plants for breeding programs.

PMID- 17546070
TI  - Development and molecular cytogenetic identification of new winter wheat--winter
      barley ('Martonvasari 9 kr1' - 'Igri') disomic addition lines.
AB  - This paper describes a series of winter wheat - winter barley disomic addition
      lines developed from hybrids between winter wheat line Triticum aestivum L.
      'Martonvasari 9 kr1' and the German 2-rowed winter barley cultivar Hordeum
      vulgare L. 'Igri'. The barley chromosomes in a wheat background were identified
      from the fluorescent in situ hybridization (FISH) patterns obtained with various
      combinations of repetitive DNA probes: GAA-HvT01 and pTa71-HvT01. The disomic
      addition lines 2H, 3H, and 4H and the 1HS isochromosome were identified on the
      basis of a 2-colour FISH with the DNA probe pairs GAA-pAs1, GAA-HvT01, and pTa71
      HvT01. Genomic in situ hybridization was used to confirm the presence of the
      barley chromosomes in the wheat genome. The identification of the barley
      chromosomes in the addition lines was further confirmed with simple-sequence
      repeat markers. The addition lines were also characterized morphologically.

PMID- 17546071
TI  - A high-resolution, intraspecific linkage map of pepper (Capsicum annuum L.) and
      selection of reduced recombinant inbred line subsets for fast mapping.
AB  - A high-resolution, intraspecific linkage map of pepper (Capsicum annuum L.) was
      constructed from a population of 297 recombinant inbred lines. The parents were
      the large-fruited inbred cultivar 'Yolo Wonder' and the hot pepper line 'Criollo
      de Morelos 334', which is heavily used as a source of resistance to a number of
      diseases. A set of 587 markers (507 amplified fragment length polymorphisms, 40
      simple sequence repeats, 19 restriction fragment length polymorphisms, 17
      sequence-specific amplified polymorphisms, and 4 sequence tagged sites) were used
      to generate the map; of these, 489 were assembled into 49 linkage groups (LGs),
      including 14 LGs with 10 to 60 markers per LG and 35 with 2 to 9 markers per LG.
      The framework map covered 1857 cM with an average intermarker distance of 5.71
      cM. Twenty-three LGs, composed of 69% of the markers and covering 1553 cM, were
      assigned to 1 of the 12 haploid pepper chromosomes, leaving 26 LGs (304 cM)
      unassigned. The chromosome framework map built with 250 markers led to a high
      level of mapping confidence and an average intermarker distance of 6.54 cM. By
      applying MapPop software, it was possible to select smaller subsets of 141 or 93
      most informative individuals with a view to reducing the time and cost of further
      mapping and phenotyping. To define the smallest number of individuals sufficient
      for assigning any new marker to a chromosome, subsets from 12 to 45 individuals
      and a set of 13 markers distributed over all 12 chromosomes were screened. In
      most cases, the markers were correctly assigned to their expected chromosome, but
      the accuracy of the map position decreased as the number of individuals was
      reduced.

PMID- 17546072
TI  - Resistance gene analogues are clustered on chromosome 3 of sugar beet and
      cosegregate with QTL for rhizomania resistance.
AB  - Worldwide, rhizomania is the most important disease of sugar beet. The only way
      to control this disease is to use resistant varieties. Four full-length
      resistance gene analogues (RGAs) from sugar beet (cZR-1, cZR-3, cZR-7, and cZR-9)
      were used in this study. Their predicted polypeptides carry typical nucleotide
      binding sites (NBSs) and leucin-rich repeat (LRR) regions, and share high
      homology to various plant virus resistance genes. Their corresponding alleles
      were cloned and sequenced from a rhizomania resistant genotype. The 4 RGAs were
      mapped as molecular markers, using sequence-specific primers to determine their
      linkage to the rhizomania resistance locus Rz1 in a population segregating for
      rhizomania resistance. One cZR-3 allele, named Rz-C, together with 5 other
      molecular markers, mapped to the Rz1 locus on chromosome 3 and cosegregated with
      quantitative trait loci for rhizomania resistance. After screening a bacterial
      artificial chromosome (BAC) library, 25 cZR-3-positive BACs were identified. Of
      these, 15 mapped within an interval of approximately 14 cM on chromosome 3, in
      clusters close to the Rz1 locus. Rz-C differentiates between susceptible and
      resistant beet varieties, and its transcripts could be detected in all rhizomania
      resistant varieties investigated. The potential of this RGA marker for cloning of
      rhizomania resistance genes is discussed.

PMID- 17546073
TI  - Genetic structure and phylogeography of rice landraces in Yunnan, China, revealed
      by SSR.
AB  - Yunnan Province is one of the largest centers of genetic diversity of Oryza
      sativa L. in China, and in the world. Using a genetically representative core
      collection of 692 rice landraces from Yunnan, the genetic structure,
      differentiation, and geographic diversity of this rice germplasm were analyzed.
      The accessions were classified into different populations, according to the model
      based structure analysis. Model-based populations were characterized through the
      reconstruction of a neighbor-joining tree, principal coordinate analysis, and the
      estimation of morphologic and SSR variations. Finally, the distribution of
      genetic diversity and differentiation among districts were studied. Seven model
      based populations were identified on the basis of the structure analysis. This
      classification was partly consistent with Ting's 5-level taxonomic system.
      Differentiation between 2 rice subspecies is the most apparent, with a clearer
      differentiation between soil-watery ecotypes in japonica than in indica; however,
      differentiation among seasonal ecotypes in indica is clearer than in japonica.
      Cropping system and man-made restricted-growth environments could be considered
      to be the main forces driving the intraspecific differentiation of cultivated
      rice. It has been suggested that, because it possesses the highest genetic
      diversity and all the necessary conditions as a center of genetic diversity, the
      southwest region of Yunnan, encompassing Simao, Lincang, and Xishuangbanna
      districts, is the center of genetic diversity of Yunnan rice landraces.

PMID- 17546074
TI  - An SSR genetic map of Sorghum bicolor (L.) Moench and its comparison to a
      published genetic map.
AB  - Sorghum bicolor (L.) Moench is an important grain and forage crop grown
      worldwide. We developed a simple sequence repeat (SSR) linkage map for sorghum
      using 352 publicly available SSR primer pairs and a population of 277 F2
      individuals derived from a cross between the Westland A line and PI 550610. A
      total of 132 SSR loci appeared polymorphic in the mapping population, and 118
      SSRs were mapped to 16 linkage groups. These mapped SSR loci were distributed
      throughout 10 chromosomes of sorghum, and spanned a distance of 997.5 cM. More
      important, 38 new SSR loci were added to the sorghum genetic map in this study.
      The mapping result also showed that chromosomes SBI-01, SBI-02, SBI-05, and SBI
      06 each had 1 linkage group; the other 6 chromosomes were composed of 2 linkage
      groups each. Except for 5 closely linked marker flips and 1 locus (Sb6_34), the
      marker order of this map was collinear to a published sorghum map, and the
      genetic distances of common marker intervals were similar, with a difference
      ratio <or= 0.05 between the 2 maps. The difference ratio is a new index developed
      in this study that can be used to compare the genetic distances of DNA markers
      between 2 maps. This SSR map carrying additional SSR markers will facilitate
      mapping quantitative trait loci to the sorghum genome and map-based gene cloning.
      Furthermore, the novel method for calculating distance between DNA markers will
      be a useful tool for the comparative analysis of genetic markers between linkage
      maps with different genetic backgrounds and the alignment of different sorghum
      genetic maps.

PMID- 17546075
TI  - AFLP analysis of genetic relationships in the genus Fosterella L.B. Smith
      (Pitcairnioideae, Bromeliaceae).
AB  - The neotropical genus Fosterella L.B. Smith (Pitcairnioideae, Bromeliaceae)
      comprises about 30 species, with a centre of diversity in semiarid to humid
      habitats of the Andean slopes and valleys of Bolivia. Morphologic differentiation
      of species is difficult because of a paucity of diagnostic characters, and little
      is known about the infrageneric phylogeny. Here, we present the results of an
      amplified fragment length polymorphism (AFLP) analysis of 77 Fosterella
      specimens, covering 18 recognized species and 9 as-yet undescribed morphospecies.
      Eight primer combinations produced 310 bands, which were scored as
      presence/absence characters. Neighbour-joining tree reconstruction revealed 12
      clusters (A-L) with various levels of support. Well-supported species groups were
      also recovered by a principal coordinates analysis. With few exceptions,
      morphologically defined species boundaries were confirmed by the molecular data.
      Phylogenetic relationships between species groups remained ambiguous, however,
      because of short internal branch lengths. The AFLP data were complemented by a
      survey of the leaf anatomy of 19 Fosterella species. Species concepts and
      assemblages are discussed in the context of molecular, morphologic, anatomic,
      ecologic, and biogeographic data. The data suggest that accidental long-distance
      dispersal and founder events have been important for Fosterella speciation.

PMID- 17546076
TI  - Haplotype diversity of preharvest sprouting QTLs in wheat.
AB  - Preharvest sprouting (PHS) is one of the most important factors affecting wheat
      production worldwide in environments characterized by rainfall and high humidity
      at harvest. In such environments, the incorporation of seed dormancy of a limited
      duration is required to minimize losses associated with PHS. A global collection
      of 28 PHS-resistant and -susceptible wheat germplasm was characterized with
      microsatellite markers flanking the genomic regions associated with PHS
      resistance quantitative trait loci (QTLs), particularly on chromosomes 3D and 4A.
      The genetic diversity analysis revealed 380 alleles at 54 microsatellite loci,
      with an average of 7.0 alleles per locus, among the 28 wheat genotypes. Gower's
      genetic similarity values among all possible pairs of genotypes varied from 0.44
      to 0.97, indicating that there is considerable diversity in the PHS germplasm
      evaluated. Cluster and principal coordinates analysis of genetic similarity
      estimates differentiated the genotypes into groups, according to their source of
      PHS resistance. Three major SSR haplotypes were observed on chromosome 4AL,
      designated RL4137-type allele, Aus1408-type allele, and synthetic-hexaploid-type
      allele. The RL4137-type allele was prevalent in Canadian cultivars, mostly in
      cluster 6, followed by the Aus1408-type and its derivatives in clusters 4 and 5.
      The Syn36 and Syn37 alleles on chromosome 4AL were rare. On chromosome 3DL, the
      SSRs haplotypes derived from Syn36 and Syn37 were also rare, and proved unique to
      the Aegilops tauschii - derived synthetic hexaploids. They are therefore likely
      carrying resistance genes different from those previously reported. Based on
      genetic relationships, PHS resistance might be improved by selecting parental
      genotypes from different clusters.

PMID- 17546077
TI  - Unisexual salamanders (genus Ambystoma) present a new reproductive mode for
      eukaryotes.
AB  - To persist, unisexual and asexual eukaryotes must have reproductive modes that
      circumvent normal bisexual reproduction. Parthenogenesis, gynogenesis, and
      hybridogenesis are the modes that have generally been ascribed to various
      unisexuals. Unisexual Ambystoma are abundant around the Great Lakes region of
      North America, and have variously been described as having all 3 reproductive
      modes. Diploid and polyploid unisexuals have nuclear genomes that combine the
      haploid genomes of 2 to 4 distinct sexual species, but the mtDNA is unlike any of
      those 4 species and is similar to another species, Ambystoma barbouri. To obtain
      better resolution of the reproductive mode used by unisexual Ambystoma and to
      explore the relationship of A. barbouri to the unisexuals, we sequenced the
      mitochondrial control and highly variable intergenic spacer region of 48
      ambystomatids, which included 28 unisexuals, representatives of the 4 sexual
      species and A. barbouri. The unisexuals have similar sequences over most of their
      range, and form a close sister group to A. barbouri, with an estimated time of
      divergence of 2.4-3.9 million years ago. Individuals from the Lake Erie Islands
      (Kelleys, Pelee, North Bass) have a haplotype that demonstrates an isolation
      event. We examined highly variable microsatellite loci, and found that the
      genetic makeup of the unisexuals is highly variable and that unisexual
      individuals share microsatellite alleles with sexual individuals within
      populations. Although many progeny from the same female had the same genotype for
      5 microsatellite DNA loci, there was no indication that any particular genome is
      consistently inherited in a clonal fashion in a population. The reproductive mode
      used by unisexual Ambystoma appears to be unique; we suggest kleptogenesis as a
      new unisexual reproductive mode that is used by these salamanders.

PMID- 17546078
TI  - Genetic maps of the proximal half of chromosome arm 2L of Drosophila
      melanogaster.
AB  - Drosophila mutants have played an important role in elucidating the physiologic
      function of genes. Large-scale projects have succeeded in producing mutations in
      a large proportion of Drosophila genes. Many mutant fly lines have also been
      produced through the efforts of individual laboratories over the past century. In
      an effort to make some of these mutants more useful to the research community, we
      systematically mapped a large number of mutations affecting genes in the proximal
      half of chromosome arm 2L to more precisely defined regions, defined by
      deficiency intervals, and, when possible, by individual complementation groups.
      To further analyze regions 36 and 39-40, we produced 11 new deficiencies with
      gamma irradiation, and we constructed 6 new deficiencies in region 30-33, using
      the DrosDel system. trans-heterozygous combinations of deficiencies revealed 5
      additional functions, essential for viability or fertility.

PMID- 17546079
TI  - Linkage maps for Arabidopsis lyrata subsp. lyrata and Arabidopsis lyrata subsp.
      petraea combining anonymous and Arabidopsis thaliana-derived markers.
AB  - Arabidopsis lyrata, a close relative of the model plant Arabidopsis thaliana, is
      1 of a few plant species for which the genome is to be entirely sequenced, which
      promises to yield important insights into genome evolution. Only 2 sparse linkage
      maps have been published, and these were based solely on markers derived from the
      A. thaliana genome. Because the genome of A. lyrata is practically twice as large
      as that of A. thaliana, the extent of map coverage of the A. lyrata genome
      remains uncertain. In this study, a 2-way pseudo-testcross strategy was used to
      construct genetic linkage maps of A. lyrata subsp. petraea and A. lyrata subsp.
      lyrata, using simple sequence repeat (SSR) and cleaved amplified polymorphic
      sequence (CAPS) markers from the A. thaliana genome, and anonymous amplified
      fragment length polymorphism (AFLP) markers that could potentially uncover
      regions unique to the A. lyrata genome. The SSR and CAPS markers largely
      confirmed the relationships between linkage groups in A. lyrata and A. thaliana.
      AFLP markers slightly increased the coverage of the A. lyrata maps, but mostly
      increased marker density on the linkage groups. We noted a much lower level of
      polymorphism and a greater segregation distortion in A. lyrata subsp. lyrata
      markers. The implications of these findings for the sequencing of the A. lyrata
      genome are discussed.

PMID- 17546080
TI  - Amphipod genome sizes: first estimates for Arctic species reveal genomic giants.
AB  - The genome sizes of 8 species of amphipods collected from the Canadian Arctic
      were estimated by flow cytometry. Haploid genome sizes ranged from 2.94 +/- 0.04
      pg DNA in Acanthostepheia malmgreni (Oedicerotidae) to 64.62 +/- 2.85 pg in
      Ampelisca macrocephala (Ampeliscidae). The value for Ampelisca macrocephala
      represents the largest crustacean genome size recorded to date (and also the
      largest within the Arthropoda) and indicates a 400-fold variation in genome size
      among crustaceans. The presence of such large genomes within a relatively small
      sample of Arctic amphipods is striking and highlights the need to further explore
      the relationships between genome size, development rates, and body size in both
      Arctic and temperate amphipods.

PMID- 17546081
TI  - Wide range QTL analysis for complex architectural traits in a 1-year-old apple
      progeny.
AB  - The present study aimed at investigating the genetic determinisms of
      architectural traits in a 1-year-old apple (Malus x domestica Borkh.). F1
      progeny. A precise phenotyping including both tree topology and geometry was
      performed on 123 offspring. For a wide range of developmental traits, broad-sense
      heritability was estimated and quantitative trait loci (QTLs) were investigated.
      Several loci controlling geometry were identified (i) for integrated traits, such
      as tree surface and volume; (ii) for traits related to the form of long sylleptic
      axillary shoots (LSAS), such as bending and basis angle; and (iii) for traits of
      finer components, such as internode length of the trunk and LSAS. Considering
      topology, 4 QTLs were mapped for the total number of sylleptic branching in the
      tree, suggesting a strong and complex genetic control that was analysed through
      colocalisations between QTLs mapped for the different shoot types (long, medium,
      short). Two QTLs were also mapped for a phenological trait (date of bud break).
      When several QTLs were detected for a trait, a linear model was built to test
      epistatic effects and estimate the whole percentage of variability explained. The
      discussion focuses on particular colocalisations and on the relevance of traits
      to further tree development.

PMID- 17546082
TI  - Mutations in acetylcholinesterase genes of Rhopalosiphum padi resistant to
      organophosphate and carbamate insecticides.
AB  - Apple grain aphid, Rhopalosiphum padi (Linnaeus), is an important wheat pest. In
      China, it has been reported that R. padi has developed high resistance to
      carbamate and organophosphate insecticides. Previous work cloned from this aphid
      2 different genes encoding acetylcholinesterase (AChE), which is the target
      enzyme for carbamate and organophosphate insecticides, and its insensitive
      alteration has been proven to be an important mechanism for insecticide
      resistance in other insects. In this study, both resistant and susceptible
      strains of R, padi were developed, and their AChEs were compared to determine
      whether resistance resulted from this mechanism and whether these 2 genes both
      play a role in resistance. Bioassays showed that the resistant strain used was
      highly or moderately resistant to pirimicarb, omethoate, and monocrotophos
      (resistance ratio, 263.8, 53.8, and 17.5, respectively), and showed little
      resistance to deltamethrin or thiodicarb (resistance ratio, 5.2 and 3.4,
      respectively). Correspondingly, biochemistry analysis found that AChE from
      resistant aphids was very insensitive to the first 3 insecticides (I50 increased
      43.0-, 15.2-, and 8.8-fold, respectively), but not to thiodicarb (I50 increased
      1.1-fold). Enzyme kinetics tests showed that resistant and susceptible strains
      had different AChEs. Sequence analysis of the 2 AChE genes cloned from resistant
      and susceptible aphids revealed that 2 mutations in Ace2 and 1 in Ace1 were
      consistently associated with resistance. Mutation F368(290)L in Ace2 localized at
      the same position as a previously proven resistance mutation site in other
      insects. The other 2 mutations, S329(228)P in Ace1 and V435(356)A in Ace2, were
      also found to affect the enzyme structure. These findings indicate that
      resistance in this aphid is mainly the result of insensistive AChE alteration,
      that the 3 mutations found might contribute to resistance, and that the AChEs
      encoded by both genes could serve as targets of insecticides.

PMID- 17546083
TI  - Genetic variation in the chloroplast genome suggests multiple domestication of
      cultivated Asian rice (Oryza sativa L.).
AB  - Two hundred and seventy-five accessions of cultivated Asian rice and 44
      accessions of AA genome Oryza species were classified into 8 chloroplast (cp)
      genome types (A-H) based on insertion-deletion events at 3 regions (8K, 57K, and
      76K) of the cp genome. The ancestral cp genome type was determined according to
      the frequency of occurrence in Oryza species and the likely evolution of the
      variable 57K region of the cp genome. When 2 nucleotide substitutions (AA or TT)
      were taken into account, these 8 cp types were subdivided into 11 cp types. Most
      indica cultivars had 1 of 3 cp genome types that were also identified in the wild
      relatives of rice, O. nivara and O. rufipogon, suggesting that the 3 indica cp
      types had evolved from distinct gene pools of the O. rufipogon - O. nivara
      complex. The majority of japonica cultivars had 1 of 3 different cp genome types.
      One of these 3 was identified in O. rufipogon, suggesting that at least 1
      japonica type is derived from O. rufipogon with the same cp genome type. These
      results provide evidence to support a polyphyletic origin of cultivated Asian
      rice from at least 4 principal lineages in the O. rufipogon - O. nivara complex.

PMID- 17546084
TI  - Mitochondrial genomic comparisons of the subterranean termites from the Genus
      Reticulitermes (Insecta: Isoptera: Rhinotermitidae).
AB  - Termites of the genus Reticulitermes are some of the most significant pests of
      structural timber and tree farming in the northern hemisphere, causing losses in
      the billions of dollars annually because of direct damage and termite control
      costs. This group has been frequently targeted for population genetic,
      phylogenetic, and species limit studies, most of which use mitochondrial (mt)
      genes; however, only a small fraction of the genome has been sequenced. The
      entire mt genome was sequenced for the eastern North American members of
      Reticulitermes: R. flavipes, R. santonensis, R. virginicus, and R. hageni. The mt
      genome has the same gene content and organization as that found in most insect
      species; however, the nucleotide composition and skew are highly biased (AT% low,
      strong A- and C-skew). Both the protein-coding and transfer RNA genes show high
      absolute levels of nucleotide substitution, suggesting that the high rates of
      mutation within Reticulitermes inferred from analyses of single mt genes are a
      general characteristic of the entire mt genome. The AT-rich or control region has
      a remarkable structure not previously observed in insect mt genomes. The majority
      of the control region is made up of 2 sets of repeat units, typically with 2 full
      and 1 partial copies of both the A (or small; 186 bp) and B (or large; 552 bp)
      repeats. The partial repeat units overlap by 36 bp. The size, location, and
      degree of overlap for the partial repeat units correspond to highly conserved
      stem/loop structures within the repeat units, suggesting that these structures
      are involved in the replication-mediated processes that govern repeat-unit
      evolution within mt genomes. Finally, molecular variation within the mt gene
      regions was compared with previous regions used in molecular diagnostics or
      phylogenetics of Reticulitermes. High numbers of single nucleotide polymorphisms
      were found in each of the mt genes, and some of the highest variability was found
      in gene regions that have not previously been investigated in this group. The
      whole mt genome sequence can thus be used to predict useful regions for future
      investigation.

PMID- 17546085
TI  - Genetic architecture of chalcone isomerase non-coding regions in common bean
      (Phaseolus vulgaris L.).
AB  - Sequence data for 2 non-coding regions of the chalcone isomerase gene were
      analyzed to study the genetic architecture of common bean (Phaseolus vulgaris
      L.). One region corresponded to the first 596 nucleotides (nt) of the 5'
      untranslated region (UTR). The other region was the 710 nt intron 3. Data were
      collected from 67 genotypes representing both landraces and cultivars from the
      geographical range of the cultivated form of the species. Variability in the 5'
      UTR region was represented by single nucleotide polymorphisms (SNPs), whereas
      intron 3 variation was due to a collection of SNPs and insertion-deletion events.
      Diversity was greater in the 5'-UTR (pi = 0.0175) than in intron 3 (pi = 0.0089).
      For each region, diversity was greater for genotypes of Middle American than
      Andean origin. A single recombination event was observed, and the hybridization
      pattern necessary to derive the recombinant genotypes supported the previous
      observation of an ancestral gene pool from which modern domesticated genotypes
      are derived. For both regions, a strongly supported Andean group was observed,
      whereas the presence of 2 Middle American subgroups was also supported. Although
      a significantly positive Tajima's D statistic was observed for the 5'-UTR for all
      genotypes, we conclude that this is more likely the result of a strong
      demographic effect and that balancing selection is occurring only among the
      Middle American genotypes.

PMID- 17546086
TI  - Sequencing cucumber (Cucumis sativus L.) chloroplast genomes identifies
      differences between chilling-tolerant and -susceptible cucumber lines.
AB  - Chilling injury in cucumber (Cucumis sativus L.) is conditioned by maternal
      factors, and the sequencing of its chloroplast genome could lead to the
      identification of economically important candidate genes. Complete sequencing of
      cucumber chloroplast (cp)DNA was facilitated by the development of 414 consensus
      chloroplast sequencing primers (CCSPs) from conserved cpDNA sequences of
      Arabidopsis (Arabidopsis thaliana L.), spinach (Spinacia oleracea L.), and
      tobacco (Nicotiana tabacum L.) cpDNAs, using degenerative primer technologies.
      Genomic sequence analysis led to the construction of 301 CCSPs and 72 cucumber
      chloroplast-specific sequencing primers (CSSPs), which were used for the complete
      sequencing of cpDNA of Gy14 (155 525 bp) and 'Chipper' (155 524 bp) cucumber
      lines, which are, respectively, susceptible and tolerant to chilling injury (4
      degrees C for 5.5 h) in the first leaf stage. Comparative cpDNA sequence analyses
      revealed that 1 sequence span (located between genes trnK and rps16) and 2
      nucleotides (located in genes atpB and ycf1) differed between chilling
      susceptible and -tolerant lines. These sequence differences correspond to
      previously reported maternally inherited differences in chilling response between
      reciprocal F1 progeny derived from these lines. Sequence differences at these 3
      cpDNA sites were also detected in a genetically diverse array of cucumber
      germplasm with different chilling responses. These and previously reported
      results suggest that 1 or several of these sequences could be responsible for the
      observed response to chilling injury in cucumber. The comprehensive sequencing of
      cpDNA of cucumber by CCSPs and CSSPs indicates that these primers have immediate
      applications in the analysis of cpDNAs from other dicotyledonous species and the
      investigation of evolutionary relationships.

PMID- 17546087
TI  - Alteration of chromosome behavior and synchronization of parental chromosomes
      after successive generations in Brassica napus x Orychophragmus violaceus
      hybrids.
AB  - In an earlier study, the progenies of intergeneric hybrids Brassica napus (2n =
      38) x Orychophragmus violaceus (2n = 24) were investigated in successive
      generations (F1-F4) for the cytological phenomenon of parental genome separation
      during mitotic and meiotic division. In the present study, inbred lines (F5-F8)
      derived from 1 such hybrid were characterized for morphology, chromosome pairing
      behaviour, and genome composition. One F5 plant (2n = 31) with slightly yellow
      petals and 12:19 and 15:16 segregation ratios in its pollen mother cells (PMCs)
      produced F6 plants with distinct morphological characteristics and wide
      variations in fertility and chromosome numbers (2n = 25-38). F7 and F8 lines with
      distinctive morphology and wide ranges in chromsome numbers were established. In
      PMCs of F7 plants from 4 F6 plants, 0-12 labelled chromosomes from O. violaceus,
      which predominantly appeared as bivalents, were identified by genomic in situ
      hybridization. They behaved synchronously with B. napus chromosomes during
      meiotic division. The results provide molecular cytogenetic evidence of the
      inclusion of O. violaceus chromosomes in the original hybrids and the cytology in
      the hybrids documented earlier. They also show that chromosome behaviour was
      altered and the parental chromosomes became synchronized after successive
      generations.

PMID- 17546088
TI  - Investigation of the origin and transmission of linear mitochondrial plasmid
      based on phylogenetic analysis in Japanese rapeseed varieties.
AB  - A linear mitochondrial plasmid is present in some varieties of rapeseed. To
      elucidate its origin and transmission the author investigated types of
      mitochondrial genome and the presence of plasmid in 78 rapeseed varieties and
      landraces in Japan and carried out a comparative analysis using the breeding
      history of Japanese rapeseed varieties. The mitochondrial genome of rapeseed was
      classified roughly into 2 types, type I (nap) and type II (cam). Type II rapeseed
      mitochondria closely resembles that of Brassica rapa, which is a related species
      of rapeseed. In this study, the author found that all varieties with type II
      mitochondria originated from interspecific crosses between rapeseed (B. napus)
      and B. rapa. This indicates that type II cytoplasm was introduced to rapeseed
      through a breeding program. The presence of plasmid was limited to B. rapa
      landraces and rapeseed varieties that arose by interspecific crosses between B.
      napus and B. rapa. The results suggest that mitochondrial plasmid is of B. rapa
      origin and that it has been introduced into rapeseed by interspecific crosses in
      a modern breeding program, as in the case of the mitochondrial genome.
      Phylogenetic study of Japanese rapeseed varieties suggests the participation not
      of the mitochondrial genome but, rather, the nuclear genome for the perpetuation
      of plasmid in progeny varieties.

PMID- 17546089
TI  - Reference karyotype and cytomolecular map for loblolly pine (Pinus taeda L.).
AB  - A reference karyotype is presented for loblolly pine (Pinus taeda L., subgenus
      Pinus, section Pinus, subsection Australes), based on fluorescent in situ
      hybridization (FISH), using 18S-28S rDNA, 5S rDNA, and an Arabidopsis-type
      telomere repeat sequence (A-type TRS). Well separated somatic chromosomes were
      prepared from colchicine-treated root meristems, using an enzymatic digestion
      technique. Statistical analyses performed on chromosome-arm lengths, centromeric
      indices, and interstitial rDNA and telomeric positions were based on observations
      from 6 well-separated metaphase cells from each of 3 unrelated trees.
      Statistically, 7 of the 12 loblolly pine chromosomes could be distinguished by
      their relative lengths. Centromeric indices were unable to distinguish additional
      chromosomes. However, the position and relative strength of the rDNA and
      telomeric sites made it possible to uniquely identify all of the chromosomes,
      providing a reference karyotype for use in comparative genome analyses. A
      dichotomous key was developed to aid in the identification of loblolly pine
      chromosomes and their comparison to chromosomes of other Pinus spp. A
      cytomolecular map was developed using the interstitial 18S-28S rDNA and A-type
      TRS signals. A total of 54 bins were assigned, ranging from 3 to 5 bins per
      chromosome. This is the first report of a chromosome-anchored physical map for a
      conifer that includes a dichotomous key for accurate and consistent
      identification of the P. taeda chromosomes.

PMID- 17546090
TI  - The mitochondrial genome structure of the clouded leopard (Neofelis nebulosa).
AB  - The complete 16 844 bp mitochondrial genome of Neofelis nebulosa has been
      sequenced and compared with the complete mitochondrial genomes of Felis catus and
      the Acinonyx jubatus. The base composition of the mitochondrial genome of N.
      nebulosa is as follows: A, 5343 bp (31.7%); C, 4441 bp (26.4%); G, 2491 bp
      (14.8%); T, 4569 bp (27.1%). The genome complement and the gene order of this
      mitochondrial genome was found to be typical of those reported for other mammals.
      Several unusual features of this genome, however, were found. First, in protein
      coding regions, AT bias in the genome was not prevalent in the third position of
      codons, as it is in most other mammals, but was found in the second position of
      codons. Second, in tRNA regions, tRNASer (AGY), which lacked the "DHU" arm, could
      not be folded into the typical cloverleaf-shaped structure. Third, in the control
      region, no repetitive sequences (RS)-2 were found. However, RS-2 repetitive
      motifs usually occurr in the control regions of most great cats. In addition, 4
      variable sites were found in CSB-3 of the control region. Fourth, AT content in
      the control region of the mtDNA from the clouded leopard was lower than it is in
      other regions.

PMID- 17546091
TI  - Correlations of geographic distribution and temperature of embryonic development
      with the nuclear DNA content in the Salamandridae (Urodela, Amphibia).
AB  - We used flow cytometry to measure the nuclear DNA content in erythrocytes of 27
      salamandrid species. Across these species, diploid genome size varied more than 2
      fold (51.3-104.4 pg). According to genome size and geographic distribution, 3
      groups of newt species were recognized: West Palearctics with smaller amounts of
      nuclear DNA; Nearctic, with intermediate values; and East Asiatic, with higher
      genome sizes. Viviparous West Palearctic salamanders differed from most of the
      oviparous West Palearctic newts in possessing larger genome sizes. The nuclear
      DNA content strongly correlates with species range limits. At the same
      temperature, embryos of salamandrid species with larger genome sizes have a
      markedly longer developmental time than those with smaller genomes. We present an
      analysis of the relationships between the amount of nuclear DNA and water
      temperature at the breeding sites.

PMID- 17546092
TI  - Screen for new mutations on the 2nd chromosome involved in indirect flight muscle
      development in Drosophila melanogaster.
AB  - An extensive ethylmethanesulfonate mutagenesis of Drosophila melanogaster was
      undertaken to isolate the stronger alleles of 3 indirect flight-muscle mutations.
      We isolated 17 strong mutant lines, with nearly complete penetrance and
      expressivity, using direct screening under polarized light, from more than 1700
      mutagenized chromosomes. On complementation, we found 11 of these 17 mutant lines
      to be alleles of 3 indirect flight-muscle mutations (Ifm(2)RU1, 3
      noncomplementing lines; ifm(2)RU2, 6 alleles; ifm(2)RU3, 2 alleles) of the
      previously isolated 8 complementation groups (Ifm(2)RU1to ifm(2)RU8). In
      addition, we found 6 new complementation groups with strong defects in adult
      muscle morphology; we named these ifm(2)RS1 to ifm(2)RS6. All mutant lines were
      mapped by meiotic recombination, and 5 of the 6 new complementation lines were
      mapped using chromosome deficiencies. ifm(2)RS1 maps to a region that harbors
      ifm(2)RU4 (a mutation that was isolated previously); however, theses are not
      alleles because each complements the other mutation, and the mutant-muscle
      phenotype is very different. We used direct screening under polarized light to
      find recessive mutations; although this method was labor intensive, it can be
      used to identify recessive genes involved in myogenesis, unlike screens for
      flightlessness or wing-position defects. This screen identifies regions on the
      second chromosome that harbor probable genes that are likely expressed in the
      mesoderm and are thought to be involved in myogenesis. This screen has generated
      valuable resources that will help us to understand the role of many molecular
      players involved in myogenesis.

PMID- 17546093
TI  - Nuclear genome size in Selaginella.
AB  - Estimates of nuclear genome size for 9 Selaginella species were obtained using
      flow cytometry, and measurements for 7 of these species are reported for the
      first time. Estimates range from 0.086 to 0.112 pg per holoploid genome (84-110
      Mb). The data presented here agree with the previously published flow cytometric
      results for S. moellendorffii. Within the 9 species sampled here, chromosome
      number varies from 2n = 16 to 2n = 27. Nuclear genome size appears to be strongly
      correlated with chromosome number (Spearman's rank correlation; p = 0.00003725).
      Cultivated S. moellendorffii lacks sexual reproduction--manifest by the
      production of abortive megasporangia. Flow cytometric data generated from a
      herbarium specimen of a fertile wild-collected S. moellendorffii are virtually
      indistinguishable from the data generated from fresh material (0.088 vs. 0.089
      pg/1C). Therefore, the limited fertility observed in cultivated plants is
      probably not the result of abnormal chromosome number (e.g., induced by
      interspecific hybridization).

PMID- 17546094
TI  - The genetic relationship among plant-height traits found using multiple-trait QTL
      mapping of a dent corn and popcorn cross.
AB  - Plant height (PH) is one of the most important traits in maize breeding programs.
      In popcorn, inferior plant traits can be improved with the dent/flint corn
      germplasm. In the current study, a total of 259 F2:3 families, developed from a
      cross between a dent corn inbred and a popcorn inbred, were evaluated for 4 PH
      traits. Quantitative trait loci (QTLs) for each trait were detected using
      composite interval mapping methods. In addition, genetic interrelationships were
      investigated using multiple-trait joint analysis for PH with ear height (EH), and
      for PH with top height (TH). In total, 6, 5, 2, and 6 QTLs were identified for
      PH, EH, TH, and TH/PH in single-trait analysis, respectively. Joint-analysis data
      suggest a strong and complex genetic relationship between PH and EH, and between
      PH and EH, with no QTLs controlling any single trait independently. In addition,
      4 kinds of QTLs detected were classified as closely linked QTLs, pleiotropic
      QTLs, QTLs with opposite effects, and additional QTLs. It was, consequently,
      difficult to improve lodge resistance through selection on any individual PH
      trait. The current study demonstrates that multiple-trait joint analysis not only
      identified additional QTLs, but also revealed the genetic relationship among
      different highly correlated traits at the molecular level.

PMID- 17546095
TI  - A natural population of the butterfly Eurema hecabe with Wolbachia-induced female
      biased sex ratio not by feminization.
AB  - In butterflies, the adult sex ratio observed in the field is usually male-biased,
      although the sex ratio of their progeny is 1:1. This is due to the higher
      motility and larger behavioral range of males than females. As expected, the sex
      ratio of Eurema hecabe butterflies collected at 6 localities throughout Japan was
      male-biased. However, in Tsukuba, located in the central part of Japan, the sex
      ratio was found to be biased toward females. Their progeny reared in the
      laboratory also exhibited a female-biased sex ratio. A single strain of Wolbachia
      is considered to be the cause of the sex-ratio distortion, because antibiotic
      treatment reversed the sex ratio to 1:1, and only a single nucleotide sequence of
      wsp, a highly variable Wolbachia gene, was detected by molecular analysis.
      Cytogenetic analysis excluded the possibility of feminization as the underlying
      mechanism. In addition, when the wild-caught females that had already mated in
      nature were treated with antibiotics before oviposition, egg-hatch rates were
      extremely low, suggesting that the same Wolbachia strain also caused cytoplasmic
      incompatibility. Our findings suggest the possibility that a single strain of
      Wolbachia induces 2 distinct reproductive manipulations in the same host.

PMID- 17546096
TI  - Relationships among durum wheat accessions. I. Comparative analysis of SSR, AFLP,
      and phenotypic data.
AB  - The determination of genetic relatedness among elite materials of crop species
      allows for more efficient management of breeding programs and for the protection
      of breeders' rights. Seventy simple sequence repeats (SSRs) and 234 amplified
      fragment length polymorphisms (AFLPs) were used to profile a collection of 58
      durum wheat (Triticum durum Desf.) accessions, representing the most important
      extant breeding programs. In addition, 42 phenotypic traits, including the
      morphological characteristics recommended for the official distinctness,
      uniformity, and stability tests, were recorded. The correlation between the
      genetic similarities obtained with the 2 marker classes was high (r = 0.81),
      whereas lower values were observed between molecular and phenotypic data (r =
      0.46 and 0.56 for AFLPs and SSRs, respectively). Morphological data, even if
      sampled in high numbers, largely failed to describe the pattern of genetic
      similarity, according to known pedigree data and the indications provided by
      molecular markers.

PMID- 17546097
TI  - Relationships among durum wheat accessions. II. A comparison of molecular and
      pedigree information.
AB  - The study of direct ancestry relationships provides information with which to
      determine essential derivation. SSR profiles were used to determine the pattern
      of relatedness among 134 durum wheat accessions, representing the most important
      modern durum wheat gene pools. Simple sequence repeat (SSR)- and amplified
      fragment length polymorphism (AFLP)-based genetic similarities among cultivars
      with accurate pedigrees were compared with pedigree-based coefficients of
      parentage. Sizeable departures of molecular similarities from the expected ones
      were observed, indicating the unreliability of inferring the pattern of genetic
      relatedness from the coefficient of parentage. Case studies consisting of parent
      progeny cultivar trios and pairs, identified on the basis of their registered
      pedigree, were studied to evaluate the probability of ancestry of each progeny
      cultivar, compared with all the remaining accessions. Rare alleles and haplotype
      sharing were also explored. When the results did not agree with the registered
      parentages, SSR markers provided information with which to identify the most
      probable parents (or the corresponding "breeding lineages") in the collection.

PMID- 17546098
TI  - CAPS markers specific to Eb, Ee, and R genomes in the tribe Triticeae.
AB  - Wild Triticeae grasses serve as important gene pools for forage and cereal crops.
      Understanding their genome compositions is pivotal for efficient use of this vast
      gene pool in germplasm-enhancement programs. Several cleaved amplified
      polymorphic sequence (CAPS) markers were developed to distinguish the Eb, Ee, and
      R genomes. With the aid of disomic addition lines of wheat, it was confirmed that
      all 7 chromosomes of Eb, Ee, and R genomes carry these genome-specific CAPS
      markers. Thus, the identified CAPS markers are useful in detecting and monitoring
      the chromosomes of these 3 genomes. This study also provides evidence suggesting
      that some Purdue and Chinese germplasm lines developed for barley yellow dwarf
      virus (BYDV) resistance are different from those developed in Australia.
      Furthermore, Thinopyrum intermedium and Thinopyrum ponticum were shown to have
      different genome constitutions. Sequence analyses of the 1272 bp sequences,
      containing Ty3/gypsy retrotransposons, from the Eb, Ee, and R genomes also shed
      light on the evolution of these 3 genomes.

PMID- 17546099
TI  - Construction, characterization, and preliminary BAC-end sequencing analysis of a
      bacterial artificial chromosome library of white clover (Trifolium repens L.).
AB  - White clover (Trifolium repens L.) is a forage legume widely used in combination
      with grass in pastures because of its ability to fix nitrogen. We have
      constructed a bacterial artificial chromosome (BAC) library of an advanced
      breeding line of white clover. The library contains 37 248 clones with an average
      insert size of approximately 85 kb, representing an approximate 3-fold coverage
      of the white clover genome based on an estimated genome size of 960 Mb. The BAC
      library was pooled and screened by polymerase chain reaction (PCR) amplification
      using both white clover microsatellites and PCR-based markers derived from
      Medicago truncatula, resulting in an average of 6 hits per marker; this supports
      the estimated 3-fold genome coverage in this allotetraploid species. PCR-based
      screening of 766 clones with a multiplex set of chloroplast primers showed that
      only 0.5% of BAC clones contained chloroplast-derived inserts. The library was
      further evaluated by sequencing both ends of 724 of the clover BACs. These were
      analysed with respect to their sequence content and their homology to the
      contents of a range of plant gene, expressed sequence tag, and repeat element
      databases. Forty-three microsatellites were discovered in the BAC-end sequences
      (BESs) and investigated as potential genetic markers in white clover. The BESs
      were also compared with the partially sequenced genome of the model legume M.
      truncatula with the specific intention of identifying putative comparative-tile
      BACs, which represent potential regions of microsynteny between the 2 species; 14
      such BACs were discovered. The results suggest that a large-scale BAC-end
      sequencing strategy has the potential to anchor a significant proportion of the
      genome of white clover onto the gene-space sequence of M. truncatula.

PMID- 17546100
TI  - Identification of plant genes regulated in resistant potato Solanum sparsipilum
      during the early stages of infection by Globodera pallida.
AB  - Using a complementary (c)DNA-amplified fragment length polymorphism (AFLP)
      approach, we investigated differential gene expression linked to resistance
      mechanisms during the incompatible potato - Globodera pallida interaction.
      Expression was compared between a resistant and a susceptible potato clone,
      inoculated or not inoculated with G. pallida. These clones were issued from a
      cross between the resistant Solanum sparsipilum spl329.18 accession and the
      susceptible dihaploid S. tuberosum Caspar H3, and carried, respectively,
      resistant and susceptible alleles at the resistance quantitative trait loci
      (QTLs). Analysis was done on root fragments picked up at 4 time points, during a
      period of 6 days after infection, from penetration of the nematode in the root to
      degradation of the feeding site in resistant plants. A total of 2560 transcript
      derived fragments (TDFs) were analyzed, resulting in the detection of 46 TDFs
      that were up- or downregulated. The number of TDFs that were up- or downregulated
      increased with time after inoculation. The majority of TDFs were upregulated at
      only 1 or 2 time points in response to infection. After isolation and sequencing
      of the TDFs of interest, a subset of 36 sequences were identified, among which 22
      matched plant sequences and 2 matched nematode sequences. Some of the TDFs that
      matched plant genes showed clear homologies to genes involved in cell-cycle
      regulation, transcription regulation, resistance downstream signalling pathways,
      and defense mechanisms. Other sequences with homologies to plant genes of unknown
      function or without any significant similarity to known proteins were also found.
      Although not exhaustive, these results represent the most extensive list of genes
      with altered RNA levels after the incompatible G. pallida-potato interaction that
      has been published to date. The function of these genes could provide insight
      into resistance or plant defense mechanisms during incompatible potato-cyst
      nematode interactions.

PMID- 17546101
TI  - Timing of thrombotic events in patients receiving 2 weeks of clopidogrel therapy
      post bare metal coronary artery stenting: a New Zealand retrospective study.
AB  - OBJECTIVE: To investigate if increased thrombotic events occurred after cessation
      of a 2-week course of clopidogrel treatment in patients who had implantation of
      bare metal stent. SETTING: Dunedin Public Hospital, a tertiary referral centre in
      New Zealand. PATIENTS: 1000 consecutive patients undergoing percutaneous coronary
      intervention (PCI) with stent implantation from January 2000 to October 2003 were
      analysed. Those who had successful implantation of bare metal stent without
      clinical events in the first 24 hours and who received 2 weeks of clopidogrel
      treatment were included in the study (n=983). MAIN OUTCOME MEASURES: Stent
      thromboses between 24 hours and 6 weeks post PCI. RESULTS: There were 13 (1.3%)
      stent thromboses between 24 hours and 6 weeks post PCI, resulting in 3 deaths
      (23%), 2 ST-elevation acute coronary syndrome [ACS] (15%), and 8 non-ST elevation
      ACS (62%). The median time for stent thrombosis was 18 +/-s 14 days. Five of the
      13 cases (38%) of stent thrombosis occurred after the first 2-weeks (1 in week 3,
      1 in week 5, 3 in week 6), and all had predisposing factors for stent thrombosis
      (2 with stent length > or = to 30 mm, 3 with stent diameter < or = to 2.5mm and 2
      with bifurcation stenting). CONCLUSION: Five of 13 (38%) stent thromboses
      occurred in week 3 to week 6 after cessation of a 2-week course of clopidogrel
      post bare metal stenting.

PMID- 17546102
TI  - Clopidogrel and stent thrombosis after percutaneous coronary intervention.

PMID- 17546103
TI  - The use of amino-terminal fraction brain natriuretic peptide (NT-proBNP) assays
      in general practices in Waikato, New Zealand.
AB  - AIMS: To assess the use of the amino-terminal fraction brain natriuretic peptide
      (NT-proBNP) assay in the management of patients with suspected heart failure in
      general practice in Waikato District Health Board (DHB). METHODS: We undertook an
      audit of all BNP requests to Waikato Health Laboratory from 1 March 2005 to 28
      February 2006 inclusive. Data were analysed for age, gender, test result, and
      requesting general practitioner (GP). Crude incidence rate of BNP test by age
      group, sex, and by district was obtained. Second tests were analysed to ascertain
      numbers of patients re-tested in primary care. RESULTS: 1553 tests were ordered
      on 1327 patients; 1182 (89%) of patients had only one test in primary care; 680
      (51.2%) of first tests were <40 pmol/L, 409 (30.8%) were between 40-220 pmol/L;
      and 238 (17.9%) were >220 pmol/L. Of the estimated 250 GPs in Waikato DHB, 75%
      (189) of GPs had requested one or more BNP tests. 27% (51/189) of GPs requested a
      repeat test on one or more patient. 27% of patients with result >220 pmol/L had a
      further BNP test in general practice. CONCLUSIONS: The majority of Waikato GPs
      have experience with BNP testing in primary care. It appears to be used
      appropriately as a tool to rule out the diagnosis of heart failure by most GPs. A
      small number of doctors appear to use BNP more frequently, possibly to monitor
      treatment or change in condition (an indication for which it is not currently
      recommended). The use of BNP varies by district.

PMID- 17546104
TI  - Interventions for severe coronary artery disease: it's not a question of can but
      a question of should.

PMID- 17546105
TI  - Surgery or percutaneous coronary intervention for three-vessel and left main
      coronary artery disease: a critical appraisal of the literature.

PMID- 17546106
TI  - Two cases of endocarditis due to Bartonella henselae.

PMID- 17546107
TI  - Living alone following first-ever stroke: a prospective study in Turkey
      identifying the risk factors and evaluating their effects.
AB  - INTRODUCTION: The incidence of stroke, death, and dependency rates shows
      variability between countries and ethnic groups. The cost of management of stroke
      is extremely high. Thus, determination of controllable risk factors is important.
      The aim of this study was to evaluate the risk factors and the effects of risk
      factors on death rates, dependency, and stroke recurrence in hospitalised
      patients having first-ever stroke. METHOD: A total of 100 patients admitting to
      our hospital during the period April 2002 to March 2003 inclusive who were
      diagnosed as stroke according to WHO criteria were included in this study and
      evaluated prospectively. RESULTS: The mean age of the patients was 66.7 +/- 9.9
      years and 60% was male. 76 of the patients had ischaemic stroke; 24 had
      hemorrhagic stroke. The death rates were 12% in the first 28 days and 26% in 6
      months. The best predictors of death rate in 6 months were stroke severity,
      living alone, and prestroke dementia. Stroke severity was also the best predictor
      for dependency. Peripheral atherosclerosis, pre-stroke dementia, and stroke
      severity were the best predictors for recurrent stroke. CONCLUSION: Living alone
      may be an important predictive factor for survival, although its importance has
      been underestimated.

PMID- 17546108
TI  - The pre-hospital phase of acute myocardial infarction: a national audit is needed
      in New Zealand.
AB  - The outcome of acute myocardial infarction is usually settled before the patient
      reaches hospital, because ventricular fibrillation, when it occurs, is most
      common soon after the onset of symptoms. Ventricular fibrillation can be treated
      as effectively by ambulance personnel as in hospital, and many more deaths can be
      prevented, mainly by timely defibrillation, for patients coming under ambulance
      care within 1 hour of onset than can be prevented by use of more recent treatment
      advances. Both patient performance in reporting symptoms promptly, and ambulance
      performance in responding to calls for help, need to be audited. A prolonged
      campaign to educate the public on the cause and symptoms of heart attack, and how
      to respond to them, is also necessary.

PMID- 17546109
TI  - Fever following appendicectomy: think about thoracic empyema.

PMID- 17546110
TI  - Hepatocutaneous fistula: a complication after radiofrequency ablation therapy for
      hepatocellular carcinoma.
AB  - A 34-year-old male was admitted for recurrent hepatocellular carcinoma (HCC) with
      poor healing of a radiofrequency ablation wound over the subxiphoid region. The
      patient underwent lobectomy of the liver 3 years previously. Transarterial
      chemoembolisation was performed twice for tumour recurrence, and radiofrequency
      ablation was done for new recurrence 2 months previously. Due to poor healing
      with discharge through the puncture wound and elevated alpha feto-protein (AFP)
      level, recurrent hepatocellular carcinoma and tumour seeding of the needle tract
      were suspected. During surgery, a recurrent tumour mass over segment 3 with a
      hepatocutaneous fistula within the adhesion tissue between the liver surface and
      abdominal wall was discovered. We recommend that hepatocutaneous fistula should
      be considered as a complication of radiofrequency ablation for hepatic tumours.

PMID- 17546111
TI  - Medical image. "Hot cross bun" sign.

PMID- 17546112
TI  - Rapid determination of fluconazole susceptibilities for clinical specimens with
      possible polymicrobial Candida spp.

PMID- 17546113
TI  - Still room for improvement in our handover practices.

PMID- 17546114
TI  - Rational pharmacoeconomics?

PMID- 17546115
TI  - A fatal error.

PMID- 17546116
TI  - What's the cost of a fees review?

PMID- 17546119
TI  - Electro-optical fiber modulation in a Sagnac interferometer.
AB  - The linear electro-optical effect was induced in optical fibers by thermal
      poling. A Sagnac all-spliced fiber loop was constructed incorporating an electro
      optical fiber used as a phase modulator at 1.5 microm and stable switching was
      obtained. A rise time of approximately 40 ns was obtained, and signals <2 V
      generated a measurable optical response.

PMID- 17546118
TI  - Broadband attosecond pulse shaping.
AB  - We use semiconductor (Si) and metallic (Al, Zr) transmission filters to shape, in
      amplitude and phase, high-order harmonics generated from the interaction of an
      intense titanium sapphire laser field with a pulsed neon gas target. Depending on
      the properties of the filter, the emitted attosecond pulses can be optimized in
      bandwidth and/or pulse length. We demonstrate the generation of attosecond pulses
      centered at energies from 50 to 80 eV, with bandwidths as large as 45 eV and with
      pulse durations compressed to 130 as.

PMID- 17546121
TI  - Converging-axicon-based radially polarized ytterbium fiber laser and evidence on
      the mode profile inside the gain fiber.
AB  - The radially polarized mode is achieved from an active Yb fiber by utilizing of
      an intracavity converging axicon, where the axicon acts as a TM(01) mode selector
      based on not only its Brewster convex surface but also the distance between its
      vertex and plane output coupler. The polarization state of the annular laser beam
      is checked by using a home-made eight-hole aperture. Furthermore, an uncoated
      plane glass plate is inserted into the cavity, and the reflected beam points to
      the existence of an annular lasing mode inside the gain fiber. The issues for
      developing high-power radially polarized fiber lasers also are considered.

PMID- 17546122
TI  - Design and fabrication of a dual-element off-axis near-eye optical magnifier.
AB  - The key contribution is the design, analysis, and fabrication of a dual-element
      off-axis magnifier to improve the state of the art in catadioptric magnifiers.
      The catadioptric magnifier is composed of a free-form mirror and a lens with a
      diffractive optical element. A monocular magnifier was prototyped, to our
      knowledge for the first time, with the specifications of an 8 mm exit pupil, 20
      degrees diagonal full field of view, 15 mm eye clearance, 1.5 arcmin resolution,
      and operating in the photopic visual regime.

PMID- 17546123
TI  - Visibility interference fringes optimization on a single beam in the case of
      partially polarized and partially coherent light.
AB  - We analyze the optimal visibility one can obtain in interference experiments with
      partially polarized light when one acts on only one of the two interfering beams.
      This is a practical situation that can appear when one does not want to modify or
      attenuate one of the beams, such as in homodyne detection. It is shown that the
      optimal configuration usually does not correspond to light with the same degrees
      of polarization for the two interfering beams. We also demonstrate that a simple
      interpretation can be obtained with the recently introduced normalized mutual
      coherence matrix.

PMID- 17546124
TI  - Squeezing the local oscillator does not improve signal-to-noise ratio in
      heterodyne laser radar.
AB  - The signal-to-noise ratio for heterodyne laser radar with a coherent target
      return beam and a squeezed local-oscillator beam is lower than that obtained
      using a coherent local oscillator, regardless of the method employed to combine
      the beams at the detector.

PMID- 17546125
TI  - Two-dimensional streaking: complete characterization of an arbitrarily polarized
      few-cycle laser pulse using a stereodetector technique.
AB  - We discuss the feasibility of measuring the temporal variation of the electric
      field strength of a few-cycle laser pulse with arbitrary polarization using the
      attosecond streaking method. It is shown that a full characterization of the
      field requires measuring the photoelectron momenta in two opposite directions in
      the laser polarization plane for various delays of the extreme ultraviolet burst
      with respect to the probed laser pulse.

PMID- 17546126
TI  - Operating characteristics of near-infrared self-assembled polymer microlasers.
AB  - We report near-infrared laser emission from self-assembled luminescent polymer
      microcavities. The microrings are formed around silica optical fibers of varying
      diameters (80, 125, and 200 microm) and are shown to exhibit photopumped lasing
      at approximately 820 nm. The microrings with 200 mum inner diameter have an
      overall quality factor of approximately 2 x 10(3), which is limited by surface
      roughness and scattering. We illustrate how the laser threshold varies inversely
      with both the quality factor and the diameter of the microrings. The free
      spectral range and the intensity variation of the laser output are also
      presented.

PMID- 17546127
TI  - Local control of light polarization with low-temperature fiber optics.
AB  - A fiber-optic-based polarization control system that uses a backreflection
      measurement scheme at low temperatures has been developed. This provides a
      stringent test of the light polarization state at the output of the fiber,
      allowing for determination and control of the degree of circular polarization;
      i.e., it can generate linear, right, or left circular polarization with cryogenic
      fibers. This polarization controller is paving the way toward the control and
      manipulation of nuclear spins in semiconductors via the optical Overhauser effect
      and could be used, for example, for the purpose of quantum information processing
      with the large nuclear spins of GaAs.

PMID- 17546128
TI  - Reducing the first-order Doppler shift in a Sagnac interferometer.
AB  - We demonstrate a technique to reduce first-order Doppler shifts in crossed
      atomic/molecular and laser beam setups by aligning two counterpropagating laser
      beams as part of a Sagnac interferometer. Interference fringes on the exit port
      of the interferometer reveal minute deviations from perfect antiparallelism.
      Residual Doppler shifts of this method scale with the ratio v/(4d) of the typical
      atomic/molecular velocity v and the laser beam diameter d. The method is
      implemented for precision frequency calibration studies at deep-UV wavelengths,
      both in one- and two-photon excitation schemes: the 6s(2) --> 6s30p(3/2)J=1 line
      in Yb at 199 nm and the 4p(6) --> 4p(5)p[1/2](0) transition in Kr at lambda=212
      nm. The achieved precision of 6 x 10(-10) is limited by the characteristics of
      the laser system.

PMID- 17546129
TI  - Femtosecond pulse shaping using a two-dimensional liquid-crystal spatial light
      modulator.
AB  - We introduce a programmable, high-rate scanning femtosecond pulse shaper based on
      a two-dimensional liquid crystal on a silicon spatial light modulator (SLM).
      While horizontal resolution of 1920 addressable pixels provides superior fidelity
      for generating complex waveforms, scanning across the vertical dimension (1080
      pixels) has been used to facilitate at least 3 orders of magnitude speed increase
      as compared with typical liquid-crystal SLM-based pulse shapers. An update rate
      in excess of 100 kHz is demonstrated.

PMID- 17546130
TI  - Continuous-wave 1.55 microm diode-pumped surface emitting semiconductor laser for
      broadband multiplex spectroscopy.
AB  - A room-temperature-operating vertical external cavity surface emitting laser is
      applied around 1550 nm to intracavity laser absorption spectroscopy analyzed by
      time-resolved Fourier-transform interferometry. At an equivalent path length of
      15 km, the high-resolution spectrum of the semiconductor disk laser emission
      covers 17 nm simultaneously. A noise-equivalent absorption coefficient at 1 s
      averaging equal to 1.5 x 10(-10) cm(-1)Hz(-1/2) per spectral element is reported
      for 65 km, the longest path length employed.

PMID- 17546131
TI  - Surface superlattice gap solitons.
AB  - We demonstrate that specific surface superlattice gap solitons can be supported
      at an interface between a one-dimensional photonic superlattice and a uniform
      medium with saturable nonlinearity. The solitons are stable in the semi-infinite
      gap but do not exist in the first gap. With the decrease of the power, the
      solitons jump from the surface site to the next one, and they may continue the
      motion into the lattices, which offers potential applications for the routing of
      optical signals.

PMID- 17546132
TI  - Effect of spatial coherence on radiation forces acting on a Rayleigh dielectric
      sphere.
AB  - We show that the radiation forces (RFs) on a Rayleigh dielectric sphere induced
      by a partially coherent light beam are greatly affected by the spatial coherence.
      We find that the magnitude of the RFs greatly decreases as the spatial coherence
      decreases and derive an inequality for the required correlation width sigma(0)
      (i.e., the spatial coherence of the beam) to stably trap the particles.

PMID- 17546133
TI  - Coherent synthesis using carrier-envelope phase-controlled pulses from a dual
      color femtosecond optical parametric oscillator.
AB  - By using a dual-color femtosecond optical parametric oscillator (OPO), a coherent
      waveform was synthesized from two coresonant near-infrared signal pulses whose
      center wavelengths had a separation of 100 nm. Immediately after the OPO cavity
      the pulses had independent carrier-envelope phase-slip frequencies, and synthesis
      was achieved by shifting these frequencies using an acousto-optic modulator
      driven by an internally generated difference frequency. Soliton self-frequency
      shifted pulses from a photonic crystal fiber and a cross-correlation frequency
      resolved optical gating (XFROG) measurement were used to analyze the result of
      the synthesis experiment and revealed that the synthesized waveform was a train
      of high-contrast 30 fs pulses.

PMID- 17546134
TI  - All-fiber pulsed lasers passively mode locked by transferable vertically aligned
      carbon nanotube film.
AB  - An all-fiber passive laser mode locking is realized with a vertically aligned
      single-walled carbon nanotube film that can be transferred onto an arbitrary
      substrate using only hot water. A D-shaped fiber is employed as the substrate for
      the evanescent field interaction of propagating light with the nanotubes. The
      scheme highlights the efficient interaction achieved by the nanotube alignment as
      well as the dramatically simplified device preparation process. The demonstrated
      pulsed laser output has 2.9 nm of spectral full width at half-maximum and a 20.8
      MHz repetition rate.

PMID- 17546135
TI  - Improvement in underwater phase measurement of an amplitude-modulated laser beam
      by polarimetric techniques.
AB  - The phase of the amplitude-modulated radiation reflected by a Lambertian target
      immersed in water was measured by using a linearly and circularly polarized
      sounding laser beam. Different values of the water extinction coefficient in the
      range of 0.06 - 2 m(-1) were realized by adding skim milk as a scattering
      element. It is shown that very efficient rejection of optical noise, resulting in
      reliable phase measurements, is accomplished with a cross-polarized and
      copolarized detection scheme for linear and circular polarization, respectively.
      The experiment demonstrates that phase measurements are very sensitive to optical
      noise suppression and that, as far as single scattering is the main involved
      mechanism, significant improvements can be achieved by adopting a polarization
      control on both the transmitter and the receiver stages of the apparatus.

PMID- 17546137
TI  - Generation of 3.5 nJ femtosecond pulses from a continuous-wave laser without mode
      locking.
AB  - Using time-lens compression in a loop configuration, we generate 516 fs pulses at
      3.5 nJ pulse energy from a continuous-wave 1.55 mum source without mode locking.
      Just as a spatial lens can expand or focus a beam in space, so can a time-lens
      broaden or compress a pulse in time. By placing a time-lens in a loop, we
      maximize the efficiency of bandwidth generation by using one time-lens driven at
      low power to emulate a stack of many lenses. Our system is compact, is all fiber,
      and allows large tuning of the repetition rate and continuous tuning of the pulse
      width and center wavelength.

PMID- 17546136
TI  - Optoelectric biosensor using indium-tin-oxide electrodes.
AB  - The use of an optically thin indium-tin-oxide (ITO) electrode is presented for an
      optoelectric biosensor simultaneously recording optical images and microimpedance
      to examine time-dependent cellular growth. The transmittance of a 100 nm thick
      ITO electrode layer is approximately the same as the transmittance of a clean
      glass substrate, whereas the industry-standard Au(47.5 nm)/Ti(2.5 nm) electrode
      layer drops the transmittance to less than 10% of that of the glass substrate.
      The simultaneous optoelectric measurements permit determining the correlation of
      the cell-covered area increase with the microimpedance increase, and the example
      results obtained for live porcine pulmonary artery endothelial cells delineate
      the quantitative and comprehensive nature of cellular attachment and spreading to
      the substrate, which has not been clearly perceived before.

PMID- 17546138
TI  - Universal generation of higher-order multiringed Laguerre-Gaussian beams by using
      a spatial light modulator.
AB  - Laguerre-Gaussian (LG) beams of various higher-order radial modes are generated
      by using a reflective phase-only liquid crystal on silicon (LCOS) spatial light
      modulator (SLM). Because of the LCOS SLM's phase-modulation characteristic of a
      wide spatial bandwidth, a phase modulation scheme effectively generates higher
      order LG beams of up to the fifth-order radial mode. We also perform correlation
      analyses between the observed and the theoretical two-dimensional mode profiles
      to universally obtain correlation coefficients of more than 0.946, which suggest
      mode generations of high quality.

PMID- 17546139
TI  - Composite frequency comb spanning 0.4-2.4 microm from a phase-controlled
      femtosecond Ti:sapphire laser and synchronously pumped optical parametric
      oscillator.
AB  - A repetition-rate-stabilized frequency comb ranging from the violet to the mid
      infrared (0.4-2.4 microm) is obtained by phase locking a femtosecond Ti:sapphire
      laser and a synchronously pumped optical parametric oscillator to a common
      supercontinuum reference. The locking results have bandwidths lower than 3 kHz.
      By changing the locking frequencies, different relative and absolute offsets of
      the constituent frequency combs are achievable.

PMID- 17546140
TI  - Dynamic speckle illumination microscopy with wavelet prefiltering.
AB  - Dynamic speckle illumination (DSI) provides a simple and robust technique to
      obtain fluorescence depth sectioning with a widefield microscope. We report a
      significant improvement to DSI microscopy based on a statistical image-processing
      algorithm that incorporates spatial wavelet prefiltering. The resultant gain in
      sectioning strength leads to a fundamentally improved scaling law for the out-of
      focus background rejection.

PMID- 17546141
TI  - Scanning near-field optical coherent spectroscopy of single molecules at 1.4 K.
AB  - We present scanning near-field extinction spectra of single molecules embedded in
      a solid matrix. By varying the tip-molecule separation, we modify the line shape
      of the spectra, demonstrating the coherent nature of the interaction between the
      incident laser light and the excited state of the molecule. We compare the
      measured data with the outcome of numerical calculations and find a very good
      agreement.

PMID- 17546142
TI  - Resonant terahertz generation from InN thin films.
AB  - Highly efficient conversion from ultrafast optical pulses to their terahertz
      (THz) counterparts has been achieved with InN thin films. An average THz output
      power as high as 0.931 microW has been obtained for an average pump power of 1 W,
      corresponding to a normalized conversion efficiency of 190% mm(-2). Based on our
      measured dependences of the THz output power on pump polarization, incident
      angle, pump power, and InN film thickness, resonance-enhanced optical
      rectification is one of the most plausible mechanisms for the THz generation in
      the InN films.

PMID- 17546143
TI  - 6450 nm wavelength tissue ablation using a nanosecond laser based on difference
      frequency mixing and stimulated Raman scattering.
AB  - A four-stage laser system was developed, emitting at a wavelength of 6450 nm with
      a 3-5 ns pulse duration, < or = 2 mJ pulse energy, and 1/2 Hz pulse repetition
      rate. The laser system successfully ablated rat brain tissue, where both the
      collateral damage and the ablation rate compare favorably with that previously
      observed with a Mark-III Free-Electron Laser.

PMID- 17546144
TI  - Slow-light switching in nonlinear Bragg-grating couplers.
AB  - We study propagation and switching of slow-light pulses in nonlinear couplers
      with phase-shifted Bragg gratings. We demonstrate that power-controlled nonlinear
      self-action of light can be used to compensate for dispersion-induced broadening
      of pulses through the formation of gap solitons, to control pulse switching in
      the coupler, and to tune the propagation velocity.

PMID- 17546145
TI  - Observation of large positive and negative lateral shifts of a reflected beam
      from symmetrical metal-cladding waveguides.
AB  - Both large positive and negative lateral shifts were observed for the reflected
      light beam on a symmetrical metal-cladding waveguide. The positive and negative
      shifts approach about 480 and 180 microm, respectively, which to our knowledge
      are the largest experimental results ever reported. The experiment also proves
      that the positive or the negative shift depends on sign of the difference between
      the intrinsic and radiative damping.

PMID- 17546146
TI  - Third-order nonlinearity of nickel oxide nanoparticles in toluene.
AB  - We report measurements of the nonlinear refractive index, n(2), of nickel oxide
      nanoparticles (NPs) in toluene at 532 nm. The measurements were performed using
      the Z-scan technique with 80 ps laser pulses at 7 Hz. Large values of n(2) in the
      range of 10(-13)-10(-12) cm(2)/W were measured, and negligible two-photon
      absorption coefficient was estimated for colloids having NP filling fractions in
      the range of 10(-8)-10(-7).

PMID- 17546147
TI  - Optical coherence tomography with plasmon resonant nanorods of gold.
AB  - We explored plasmon resonant nanorods of gold as a contrast agent for optical
      coherence tomography (OCT). Nanorod suspensions were generated through wet
      chemical synthesis and characterized with spectrophotometry, transmission
      electron microscopy, and OCT. Polyacrylamide-based phantoms were generated with
      appropriate scattering and anisotropy coefficients (30 cm(-1) and 0.89,
      respectively) to image distribution of the contrast agent in an environment
      similar to that of tissue. The observed signal was dependent on whether the
      plasmon resonance peak overlapped the source bandwidth of the OCT, confirming the
      resonant character of enhancement. Gold nanorods with plasmon resonance
      wavelengths overlapping the OCT source yielded a signal-to-background ratio of
      4.5 dB, relative to the tissue phantom. Strategies for OCT imaging with nanorods
      are discussed.

PMID- 17546148
TI  - Autocorrelation artifacts in optical coherence tomography and interferometric
      synthetic aperture microscopy.
AB  - Interferometric synthetic aperture microscopy processing of optical coherence
      tomography data has been shown to allow computational focusing of en face planes
      that have traditionally been regarded as out of focus. It is shown that this
      focusing of the image also produces a defocusing effect in autocorrelation
      artifacts resulting from Fourier-domain data collection. This effect is verified
      experimentally and through simulation.

PMID- 17546149
TI  - Method for designing an arbitrary continuous refracting surface with specified
      property of wavefronts conversion.
AB  - A method is proposed for designing an arbitrary continuous refracting surface
      that can realize conversion between two specified distributions of wavefront.
      Optimization technique is avoided by solving a partial differential equation
      governing the surface-profile function. This equation is obtained using the
      property of congruence and the law of refraction, and its solution in this
      special case is found to be the same as that obtained in wavefront conjugation. A
      method based on finding the local coefficients of the surface is developed to
      solve the equation numerically, and an example is given to illustrate its
      feasibility.

PMID- 17546150
TI  - Nonlinearly controlled angular momentum of soliton clusters.
AB  - We demonstrate an original approach, to the best of our knowledge, to acquire
      nonlinear control over the angular momentum of a cluster of solitary waves. We
      show that the angular momentum can be adjusted by acting on the global excitation
      of the system. The effect is verified in liquid crystals by observing power
      dependent rotation of a two-soliton cluster.

PMID- 17546151
TI  - Limitations of the tunability of dual-crystal optical parametric oscillators.
AB  - We demonstrate what is believed to be the first continuous-wave dual-crystal
      optical parametric oscillator (D-OPO) for generation of waves with a frequency
      difference of some terahertz. It is based on two magnesium-doped periodically
      poled lithium niobate crystals pumped with near-infrared light at 1030 nm. By
      changing the temperature difference of the crystals we achieve a difference
      frequency tuning. This ranges from an initially unexpected lower threshold of 1.3
      THz up to higher frequencies. The linewidth of the considered signal waves is
      smaller than 5 GHz. Smaller difference frequencies were not achievable. Our
      model, describing the dual-crystal parametric gain, explains the observed lower
      tuning limit by showing that the assumption of independent oscillation conditions
      in a D-OPO is not necessarily valid.

PMID- 17546152
TI  - Characterization of Fourier components in type I infrared ultrafast laser induced
      fiber Bragg gratings.
AB  - Type I infrared ultrafast laser induced fiber Bragg gratings have been shown to
      exhibit higher-order resonances related to the Fourier components possessed by
      their nonsinusoidal index change profile. Using successive higher-order phase
      masks, we determine the Fourier components of type I-IR gratings in both hydrogen
      loaded and unloaded fiber. Knowledge of the relative dc and ac components of a
      fiber Bragg grating is required for tailoring its spectral response.

PMID- 17546153
TI  - Accurate phase-shifting digital interferometry.
AB  - In phase-shifting interferometry experiments, the accuracy of the phase shift is
      a major issue. Many experimental and data analyses are done to cancel phase-shift
      errors inherent to the modulation techniques used. We propose to remove most of
      the phase-shift error by recourse to a frequency-shifting method. This approach
      can be applied to both holography and interferometry. We validate the idea with a
      holographic experiment.

PMID- 17546154
TI  - Femtosecond laser writing of porous capillaries inside fused silica glass.
AB  - We demonstrate that within a restricted optical pulse duration-pulse energy
      parameter space tightly focused femtosecond laser radiation can be used to
      fabricate porous capillaries in bulk fused silica glass by simply moving the
      laser focus through the material. We show that the rate of penetration of liquids
      into the porous capillaries can be controlled by the laser polarization, which
      determines their morphology. The fluid propagation is measured using the form
      birefringence of nanocrack/nanovoid structures produced inside the capillaries.
      We also demonstrate the nanofiltration capabilities of the capillaries by
      separating the relatively small molecules of Rhodamine 6G dye from their solvent.

PMID- 17546155
TI  - Diode-pumped Pr(3+):KY(3)F(10) red laser.
AB  - We report the first observation to our knowledge of room-temperature continuous
      wave laser operation of a Pr(3+):KY(3)F(10) single crystal at 644.5 nm, pumped by
      a blue GaN laser diode emitting at 446 nm. With a 2.5% transmission output
      coupler and a nonoptimized optical cavity, an output power of 39 mW was obtained
      at 644.5 nm with a laser threshold of 125 mW and a differential slope efficiency
      of 23%.

PMID- 17546156
TI  - Numerical solution of inverse scattering for near-field optics.
AB  - A novel regularized recursive linearization method is developed for a two
      dimensional inverse medium scattering problem that arises in near-field optics,
      which reconstructs the scatterer of an inhomogeneous medium located on a
      substrate from data accessible through photon scanning tunneling microscopy
      experiments. Based on multiple frequency scattering data, the method starts from
      the Born approximation corresponding to weak scattering at a low frequency, and
      each update is obtained by continuation on the wavenumber from solutions of one
      forward problem and one adjoint problem of the Helmholtz equation.

PMID- 17546157
TI  - Efficient extracavity generation of radially and azimuthally polarized beams.
AB  - We demonstrate an efficient transformation of a linearly polarized Gaussian beam
      to a radially or an azimuthally polarized doughnut (0,1)* Laguerre-Gaussian beam
      of high purity. We use a spatially variable retardation plate, composed of eight
      sectors of a lambda/2 retardation plate, to transform a linear polarization
      distribution to radial/azimuthal distribution. We transformed an Nd:YAG Gaussian
      beam with M(2)=1.3 to a radially and azimuthally polarized (0,1)* Laguerre
      Gaussian beams with M(2)=2.5 and degree of radial/azimuthal polarization of 96
      98%.

PMID- 17546158
TI  - Maximum visibility under unitary transformations in two-pinhole interference for
      electromagnetic fields.
AB  - In terms of the spectral density tensors associated with the electric field
      vector, the maximum visibility one can obtain in a two-point interference
      arrangement by using local (i.e., position-dependent) unitary transformations
      applied at such points is determined. It is also shown that the maximum
      visibility can be expressed in terms of a number of well-known parameters
      describing the coherence and polarization features of the field.

PMID- 17546159
TI  - All-fiber mode-locked fiber laser.
AB  - An environmentally stable mode-locked fiber laser based on nonlinear polarization
      rotation is experimentally demonstrated. The laser is based on a novel laser
      configuration that has negligible low-power steady-state reflectivity from one
      side and, consequently, no CW gain. The laser is self starting and the
      configuration is implementable as an all-fiber laser with standard polarization
      maintaining fiber-pigtailed components. A pulse duration of 5.6 ps is obtained at
      a repetition rate of 5.96 MHz and at an average power of 8 mW. As an application
      of the proposed laser configuration, 213 mW of supercontinuum (600-1750 nm) was
      demonstrated from a fiber laser system with no sections of free-space optics.

PMID- 17546160
TI  - Proposal for all-optical format conversion based on a periodically poled lithium
      niobate loop mirror.
AB  - We propose and simulate two novel schemes of 40 Gbit/s format conversion from non
      return-to-zero to return-to-zero based on cascaded second-harmonic generation and
      difference-frequency generation in a periodically poled lithium niobate loop
      mirror. We investigate the conversion performance, including eye diagrams,
      conversion efficiency, pulse width, Q-factor, extinction ratio, and tunability.
      The proposed schemes can perform single-to-dual-channel format conversion. In
      addition, it is found that simultaneous multichannel format conversion as well as
      tunable multicasting format conversion can potentially be implemented with great
      flexibility.

PMID- 17546161
TI  - AlGaInAs quantum-well as a saturable absorber in a diode-pumped passively Q
      switched solid-state laser.
AB  - We demonstrate what is believed to be the first use of AlGaInAs quantum wells
      (QWs) as a saturable absorber in the Q switching of a high-power diode-pumped Nd
      doped 1.06 mum laser. The barrier layers are designed to locate the QW groups in
      the region of the nodes of the lasing standing wave to avoid damage. With an
      incident pump power of 13.5 W, an average output power of 3.5 W with a Q-switched
      pulse width of 0.9 ns at a pulse repetition rate of 110 kHz was obtained.

PMID- 17546162
TI  - Strong-interaction-mediated critical coupling at two distinct frequencies.
AB  - I study a multilayered medium consisting of a metal-dielectric composite film, a
      spacer layer, and a dielectric Bragg reflector. I demonstrate a greater
      flexibility over the critical coupling phenomenon [Tischler et al., Opt. Lett.
      31, 2045 (2006)], whereby nearly all the incident light energy is absorbed by the
      composite film through suppression of both transmission and reflection from the
      structure. For a larger volume fraction of the metal inclusions, strong light
      matter coupling is shown to lead to almost total absorption at two distinct
      frequencies.

PMID- 17546163
TI  - Stable high-power continuous-wave Yb(3+)-doped silica fiber laser utilizing a
      point-by-point inscribed fiber Bragg grating.
AB  - We report on a narrowband 5 W cw fiber laser incorporating a point-by-point fiber
      Bragg grating inscribed into the core of a Yb(3+)-doped double-clad fiber. The
      laser featured excellent long-term wavelength and power stability (0.3%), as well
      as a very narrow (15 pm) linewidth, when passive temperature stabilization of the
      grating was implemented.

PMID- 17546164
TI  - Near-infrared optical parametric amplifier at 1 MHz directly pumped by a
      femtosecond oscillator.
AB  - We demonstrate a high-average-power optical parametric amplifier directly pumped
      by a cavity-dumped Yb:KYW mode-locked laser oscillator at 1 MHz repetition rate.
      The two-stage system uses periodically poled lithium niobate crystals both for
      optical parametric generation and for power amplification. We obtain average
      powers as high as 190 mW with 220 fs average pulse widths and wavelength
      tunability in the 1.3-1.6 microm (signal) and 3.1-4.6 microm (idler) range.

PMID- 17546165
TI  - Passive broadband silicon-on-insulator polarization splitter.
AB  - We present the implementation of a novel wavelength independent polarization
      splitter on a silicon-on-insulator platform. The waveguide splitter is based on a
      zero-order arrayed waveguide grating (AWG) configuration. The splitting function
      is realized by employing cladding stress-induced birefringence. The device
      demonstrated a TE to TM splitting ratio better than -15 dB over a 20 nm tuning
      range centered around lambda=1550 nm and better than -10 dB over our entire
      accessible wavelength range from lambda=1465 nm to 1580 nm. The highest splitting
      extinction ratio achieved was -20 dB. To our knowledge, this is the first
      reported passive broadband polarization splitter based on AWG.

PMID- 17546166
TI  - High efficiency grating coupler between silicon-on-insulator waveguides and
      perfectly vertical optical fibers.
AB  - A high-efficiency waveguide-to-fiber grating coupler for silicon-on-insulator
      waveguides was designed. Perfectly vertical fiber coupling is achieved by using
      an asymmetric grating structure to suppress the second-order Bragg reflection
      from the grating. The ability to use a perfectly vertical positioned optical
      fiber simplifies the packaging of the photonic integrated circuit. A coupling
      efficiency of 80% at a wavelength of 1.55 microm is obtained.

PMID- 17546167
TI  - Demonstration of a spatial filtering amplifier for high-order harmonics.
AB  - We report what is to our knowledge the first demonstration of spatial filtering
      of a high-order harmonic beam into a soft-x-ray laser plasma amplifier at 32.8
      nm. After amplification the seed energy is enhanced by a factor of 50, and the
      beam profile of the amplified beam exhibits an Airy-like shape due to the spatial
      filtering by the optical field ionized plasma. Moreover, the transverse coherence
      of the spatially filtered amplified beam is strongly enhanced, resulting in the
      generation of a peak coherent power of 0.9 x 10(5) to 1.8 x 10(5) W.

PMID- 17546168
TI  - Realization of receptive fields with excitatory and inhibitory responses on
      equilibrium-state luminescence of electron trapping material.
AB  - Our theoretical modelings and experimental observations illustrate that the
      equilibrium-state luminescence of electron-trapping materials (ETMs) can be
      controlled to produce either excitatory or inhibitory responses to the same
      optical stimulus. Because of this property, ETMs have a unique potential in
      optical realization of neurobiologically based parallel computations. As a
      classic example, we have controlled the equilibrium-state luminescence of a thin
      film of this stimulable storage phosphor to make it behave similarly to the
      receptive fields of sensory neurons in the mammalian visual system, which are
      responsible for early visual processing.

PMID- 17546169
TI  - Relation between degrees of coherence for electromagnetic fields.
AB  - In terms of the electric spectral density tensors associated with a random
      electromagnetic field, it is shown that, under certain conditions, a link can be
      established between two definitions of the degree of coherence for
      electromagnetic beams introduced not long ago by Wolf [Phys. Lett. A312, 263
      (2003)] and by Setala [Opt. Lett.29, 328 (2004)]. This connection is formulated
      as a certain equivalence relationship concerning the behavior of the above
      degrees of coherence and the degree of polarization of the field at two points.

PMID- 17546170
TI  - Entangled symplectic wavelet transformation.
AB  - The symplectic wavelet transformation proposed in Opt. Lett. 31, 3432 (2006),
      which is related to the optical Fresnel transform in the quantum optics version,
      is developed into an entangled symplectic wavelet transformation (ESWT) after
      pointing out the contrast between the single-mode Fresnel operator and the
      entangled Fresnel operator. The ESWT possesses well-behaved properties and
      corresponds to the entangled Fresnel transform [Phys. Lett. A334, 132 (2005)].

PMID- 17546171
TI  - Comment on "Negative refractive index in artificial metamaterials".
AB  - We dispute Grigorenko's statement [Opt. Lett. 31, 2483 (2006)] that measuring
      only the reflection intensity spectrum is sufficient for determining the
      effective refractive index. In addition, our simulations do not confirm his
      conclusions regarding the negative refractive index and the negative permeability
      of the nanopillar sample in the visible range.

PMID- 17546172
TI  - Reply to comment on "Negative refractive index in artificial metamaterials".
AB  - The claims of the preceding Comment [Opt. Lett. 32, 1510 (2007)] are discussed.
      It is shown that Kildishev misread the previously presented method [Opt. Lett.
      31, 2483 (2006)] for determining optical constants of nanostructured films.
      Reasons for a disagreement of the simulations presented in the Comment are also
      discussed.

PMID- 17546173
TI  - Asymptotic formalism for ultraflat optical frequency comb generation using a Mach
      Zehnder modulator.
AB  - We theoretically prove that a conventional Mach-Zehnder modulator can generate an
      optical frequency comb with excellent spectral flatness. The modulator is
      asymmetrically dual driven by large amplitude sinusoidal signals with different
      amplitudes. The driving condition to obtain spectral flatness is analytically
      derived and optimized, yielding a simple formula. This formula also predicts the
      conversion efficiency and bandwidth of the generated frequency comb.

PMID- 17546174
TI  - Dynamic spectral imaging with spectral zooming capability.
AB  - We report a dynamic spectral imaging system with spectral band zooming and
      selection capability that can adapt to different application requirements and
      significantly reduce the size of the captured spectral image data cube. It
      employs a diffraction grating to disperse the spectral information of the
      captured image and uses a dynamic spatial filter at the Fourier plane to select
      the spectral channel and spectral bandwidth for each spectral image. With a
      limited fixed spectral channel number, it can provide both coarse and fine
      spectral image viewing and capture. A prototype spectral imaging system with such
      spectral band zooming and selection features has been constructed. Spectral
      zooming from 9 to 50 nm resolution has been demonstrated.

PMID- 17546175
TI  - Fractionalization of optical beams: I. Planar analysis.
AB  - We apply the tools of the fractional calculus to introduce new fractional-order
      beam solutions to the paraxial wave equation that can be regarded as intermediate
      solutions between the known integral-order solutions. We restrict our attention
      to the fractionalization of the elegant and standard Hermite-Gaussian beams.

PMID- 17546176
TI  - Polarization controller for hollow-core fiber.
AB  - We demonstrate a universal polarization controller for hollow-core fibers, a
      simple device consisting of three twisted fiber sections that makes use of the
      inherent birefringence of the air-core fiber. The device 5% bandwidth at 1550 nm
      is calculated from measured data to be approximately 13 nm.

PMID- 17546177
TI  - Spontaneous emission in coupled microcavity-waveguide structures at the band
      edge.
AB  - We examine spontaneous emission and photon dynamics in a microcavity coupled to a
      coupled-resonator optical waveguide (CROW) in a photonic crystal. We present an
      efficient tight-binding approach to obtain the Green tensor in large, arbitrary
      systems of coupled microcavities. We use this approach to examine spontaneous
      emission when the microcavity is strongly coupled to the CROW at the band center
      and band edge. We confirm the validity of weak-coupling theories for
      microcavities resonant at band center and obtain strong peak splitting in the
      previously inaccessible case of band-edge coupled structures.

PMID- 17546178
TI  - Linearly polarized, 3.35 W narrow-linewidth, 1150 nm fiber master oscillator
      power amplifier for frequency doubling to the yellow.
AB  - A high-power linearly polarized Yb-doped silica fiber master oscillator power
      amplifier at 1150 nm is reported. It produced 3.35 W cw and 2.33 W of average
      power in 1 micros pulses at a 100 kHz repetition rate, both with 8 pm linewidth.
      This is the first report, to the best of our knowledge, of a high-power Yb-doped
      fiber amplifier at a wavelength longer than 1135 nm. The pulsed output was
      frequency doubled in a bulk periodically poled near-stoichiometric LiTaO(3) chip
      to generate 976 mW of average power at 575 nm with an overall system optical-to
      optical efficiency of 9.8% with respect to launched pump power.

PMID- 17546179
TI  - Angular tolerance of Shack-Hartmann wavefront sensors with microaxicons.
AB  - Wavefront sensing under nonparaxial conditions was studied with Shack-Hartmann
      setups based on arrays of microaxicons. The robustness of the generated
      pseudonondiffracting subbeams against tilt and axial displacement was
      demonstrated for ultraflat Gaussian- and inverse-Gaussian-shaped elements in
      transmission and reflection. To characterize slight aberrations and to identify
      optimum parameter fields, spatial moments of intensity profiles were analyzed
      with high sensitivity. Reflective design enables for wavefront sensing at oblique
      incidence as necessary for low-feedback detection and phase diagnostics of
      ultrashort pulses.

PMID- 17546180
TI  - Fabrication of microfluidic optical waveguides on glass chips with femtosecond
      laser pulses.
AB  - We describe the fabrication of microfluidic channel structures on the surface of
      a borosilicate glass slide by femtosecond laser direct writing for optical
      waveguide application. Liquid with a variable refractive index is fed into the
      microchannel, serving as the core of the waveguide. We demonstrate that either a
      multimode or a single-mode waveguide can be achieved by controlling the
      refractive index of the liquid.

PMID- 17546181
TI  - Toward an understanding of white-light generation in cubic media - polarization
      properties across the entire spectral range.
AB  - We present an extensive investigation of the polarization properties of a
      femtosecond-laser-induced white-light (WL) continuum generated in a cubic crystal
      (CaF(2)). The WL spectrum and threshold energies have been examined for input
      polarizations with various degrees of ellipticity. For linear input polarization,
      the WL spectrum shows strong depolarization around the input wavelength, while
      the preservation of the input polarization is pronounced toward the blue spectral
      region. The observed depolarization effect has been elucidated in the framework
      of current models for WL generation.

PMID- 17546182
TI  - Demonstration of 100 GHz electrically tunable liquid-crystal Bragg gratings for
      application in dynamic optical networks.
AB  - We demonstrate liquid-crystal-based integrated optical devices with >140 GHz
      electrical tuning for potential applications in dynamic optical networks. Bragg
      wavelength tuning covering five 25 GHz wavelength-division multiplexing channel
      spacing has been achieved with 170 V (peak-to-peak) sinusoidal voltages applied
      across electropatterned indium tin oxide-covered glass electrodes placed 60
      microm apart. This tunability range was limited only by the initial grating
      strength and supply voltage level. We also observed two distinct threshold
      behaviors that manifest during increase of supply voltage, resulting in a
      hysteresis in the tuning curve for both TE and TM input light.

PMID- 17546183
TI  - Ultrashort single-shot pulse characterization with high spatial resolution using
      localized nonlinearities in ferroelectric domain walls.
AB  - Second-order nonlinearities localized in the regions adjacent to the
      ferroelectric domain wall in KTiOPO(4) are used to realize a single-shot
      noncollinear frequency-resolved optical gating arrangement for ultrashort pulse
      characterization with high spatial resolution. Cerenkov phase matching is
      utilized to achieve spectral dispersion and makes the same nonlinear crystal
      applicable over wide spectral ranges from the visible to the mid-infrared.

PMID- 17546184
TI  - Monolithic optical parametric oscillator using chirped quasi-phase matching.
AB  - We describe a highly efficient monolithic, Q-switched, nanosecond optical
      parametric oscillator based on a magnesium-oxide-doped periodically poled lithium
      niobate crystal and containing multiple quasi-phase-matched gratings. The crystal
      consisted of a single unchirped grating and five gratings containing
      progressively increasing amounts of longitudinal chirp. The monolithic design
      makes the device highly compact, stable, and robust, and it demonstrated a pump
      to-signal conversion efficiency of around 50%, generating 50 microJ pulses at
      1.55 microm with a spectral bandwidth of 20 nm. Sonogram traces are presented
      showing the effect of crystal chirp on the temporal and spectral performance.

PMID- 17546185
TI  - Millijoule pulse energy Q-switched short-length fiber laser.
AB  - We report on a Q-switched short-length fiber laser producing 100 W of average
      output power at 100 kHz repetition rate and pulse durations as short as 17 ns. Up
      to 2 mJ of energy and sub-10-ns pulse duration are extracted at lower repetition
      rates. This performance is obtained by employing a rod-type ytterbium-doped
      photonic crystal fiber with a 70 microm core as gain medium, allowing for very
      short pulse durations, high energy storage, and emission of a single-transverse
      mode beam.

PMID- 17546186
TI  - Strongly enhanced mode selection in a thin dielectric-coated layered microcavity
      laser.
AB  - Strong mode selection through an enhanced interferential coupling effect was
      observed in a thin dielectric-coated layered cylindrical microcavity laser. The
      strong coupling effect was induced owing to an enhanced reflectivity of around
      50% at the dielectric-coated inner boundary of a fused silica capillary filled
      with a dye-doped liquid. At an optimized coating thickness of about 0.4 microm,
      the lasing peaks appeared only at the wavelengths corresponding to the
      constructive interference condition, whereas those from a bare capillary were
      weakly modulated.

PMID- 17546187
TI  - Coupling of whispering-gallery modes in size-mismatched microdisk photonic
      molecules.
AB  - Mechanisms of whispering-gallery (WG)-mode coupling in microdisk photonic
      molecules (PMs) with slight and significant size mismatches are numerically
      investigated. The results reveal two different scenarios of modes interaction
      depending on the degree of this mismatch and offer new insight into how PM
      parameters can be tuned to control and modify WG-mode wavelengths and Q factors.
      From a practical point of view, these findings offer a way to fabricate PM
      microlaser structures that exhibit low thresholds and directional emission and at
      the same time are more tolerant to fabrication errors than previously explored
      coupled-cavity structures composed of identical microresonators.

PMID- 17546189
TI  - Mode coupling between first- and second-order whispering-gallery modes in coupled
      microdisks.
AB  - The mode characteristics for two coupled microdisks are investigated by the
      finite-difference time-domain technique. In the two coupled micodisks, mode
      coupling between the same order whispering-gallery modes (WGMs) results in
      coupled WGMs with split mode wavelengths. The numerical results show that the
      split mode wavelengths of the coupled first- and second-order WGMs can have a
      crossing point in some cases, which can induce anticrossing mode coupling between
      them and greatly reduce the mode Q factor of the coupled first-order WGMs. The
      time variation of mode field pattern shows the transformation between the coupled
      first- and second-order WGMs.

PMID- 17546188
TI  - Estimation of the scattering coefficients of turbid media using angle-resolved
      optical frequency-domain imaging.
AB  - Noninvasive measurements of the scattering coefficients of optically turbid media
      using angle-resolved optical frequency-domain imaging (OFDI) are demonstrated. It
      is shown that, by incoherently averaging OFDI reflectance signals acquired at
      different backscattering angles, speckle noise is reduced, allowing scattering
      coefficients to be extracted from a single A-line with much higher accuracy than
      with measurements from conventional OFDI and optical coherence tomography
      systems. Modeling speckle as a random phasor sum, the relationship between the
      measurement accuracy and the number of compounded angles is derived. The
      sensitivity analysis is validated with measurements from a tissue phantom.

PMID- 17546190
TI  - High repetition rate, low jitter, low intensity noise, fundamentally mode-locked
      167 fs soliton Er-fiber laser.
AB  - A fundamentally mode-locked soliton Er-fiber laser generating 167 fs pulses at
      194 MHz via polarization additive-pulse mode locking is demonstrated. This
      simple, compact, and high repetition rate source exhibits a low timing jitter of
      18 fs [1 kHz, 10 MHz] and the lowest relative intensity noise of less than 0.003%
      [1 kHz, 10 MHz] observed from an Er-fiber laser.

PMID- 17546191
TI  - Single-shot imaging of ground-state hydrogen atoms with a nonlinear laser
      spectroscopic technique.
AB  - We report on a novel nonlinear laser spectroscopic technique for single-shot
      imaging of ground-state hydrogen atoms in harsh environments. H atoms from the
      ground state were first pumped to the 2s state via a two-photon excitation with a
      243 nm laser beam, and the population of the 2s state was further probed through
      the 2s-4p transition with conventional polarization spectroscopy at 486 nm. A
      single Nd:YAG-pumped optical parametric oscillator laser system was enough to
      provide both laser beams. Single-shot visualization of native H atoms in an
      atmospheric pressure premixed H(2)/O(2) flame is demonstrated.

PMID- 17546192
TI  - Imaging voltage-dependent cell motions with heterodyne Mach-Zehnder phase
      microscopy.
AB  - We describe a heterodyne Mach-Zehnder interferometric microscope capable of
      quantitative phase imaging of biological samples with subnanometer sensitivity
      and frame rates up to 10 kHz. We use the microscope to image cultured neurons and
      measure nanometer-scale voltage-dependent motions in cells expressing the
      membrane motor protein prestin.

PMID- 17546193
TI  - Micromachining structured optical fibers using focused ion beam milling.
AB  - A focused ion beam is used to mill side holes in air-silica structured fibers. By
      way of example, side holes are introduced in two types of air-structured fiber,
      (1) a photonic crystal four-ring fiber and (2) a six-hole single-ring step-index
      structured fiber.

PMID- 17546194
TI  - Nanometer-thick Au-films as antireflection coating for infrared light.
AB  - The optical properties of ultrathin Au films on silicon have been studied in the
      infrared over a wide frequency range from 200 to 10,000 cm(-1). Thick films show
      a Drude behavior; i.e., with increasing frequency the transmission increases; for
      films below the percolation threshold at about 5 nm a negative slope for the
      frequency-dependent transmission is observed. When the thickness is further
      reduced, between 1 and 3 nm an anomaly occurs: the relative transmission reaches
      maximum values above 100% compared with the bare substrate, indicating an
      antireflection coating of nanometer thickness for light of 5 microm wavelength.
      This anomaly can be explained in the framework of effective-medium theories.

PMID- 17546195
TI  - Generation of multiple gain-guided solitons in a fiber laser.
AB  - We report the experimental observation of multiple gain-guided solitons in an
      erbium-doped fiber laser made of all normal-dispersion fibers. Numerical
      simulations show that, in the case of a narrow gain bandwidth, under the action
      of the cavity pulse peak clamping effect multiple gain-guided solitons can indeed
      be formed in a laser.

PMID- 17546196
TI  - Wavefront sensing with random amplitude mask and phase retrieval.
AB  - A light beam with an ideal wavefront that is transmitted or reflected from an
      object is modified by different characteristics of the object such as shape,
      refractive index, density, or temperature. Wavefront sensing therefore yields
      valuable information about the system or the changes happening to the system. A
      new method for wavefront sensing using a random amplitude mask and a phase
      retrieval method based on the Rayleigh-Sommerfeld wave propagation equation is
      described. The proposed method has many potential applications ranging from phase
      contrast imaging and measurement of lens aberration to shape measurement of three
      dimensional objects.

PMID- 17546197
TI  - Quantification of a three-dimensional velocity vector using spectral-domain
      Doppler optical coherence tomography.
AB  - Multiangle, fiber-based, spectral-domain Doppler optical coherence tomography
      with a phase-resolved algorithm is presented to measure three components of an
      arbitrary velocity vector. A beam divider that divides a probe beam to have five
      independent viewpoints and path length delays was designed. The divider was
      inserted into the sampling arm of a Doppler optical coherence tomography system
      between the collimator and the first galvo mirror of a two-axis galvo scanner.
      The divider produced five independent D k's (the average difference between the
      wave vectors of incoming and outgoing beams) after passing through the focusing
      lens while keeping two-axis scanning capability. After calibration, an unknown
      velocity vector field inside a microtube was quantified by solving a three
      dimensional minimization problem.

PMID- 17546198
TI  - Observation of interference in reflection profile resulting from excitation of
      optical normal modes with focused beams.
AB  - We report the observation of novel interference patterns in reflected beam
      profiles resulting from the excitation with a focused laser beam of both the long
      range surface plasmon mode and leaky waveguide modes in a prism-coupled thin-film
      geometry. Many new features of the observation are in good agreement with the
      theory; namely, the greater than unity normalized peak interference intensities,
      the monotonically decreasing spacing between the periodic intensity variations,
      and the reshaping of the reflected profile due to propagation. Implications of
      these results for submicrometer patterning in nanoscience are pointed out.

PMID- 17546199
TI  - Microjoule pulses from a passively mode-locked Yb:KY(WO(4))(2) thin-disk
      oscillator with cavity dumping.
AB  - We demonstrate, for the first time to our knowledge, a passively mode-locked
      femtosecond thin-disk oscillator with cavity dumping. A beta-barium-borate-based
      pockels cell imposes cavity dumping at a repetition rate of 1 MHz. The laser
      generates pulse energies up to 3 microJ with a pulse duration of 680 fs in a
      diffraction-limited beam.

PMID- 17546200
TI  - Generation of in-phase pulse train from optical beat signal.
AB  - We propose and demonstrate generation of an in-phase optical pulse train from an
      optical beat signal. The proposed method is based on four-wave mixing occurring
      between the two continuous waves of the beat signal and on spectral filtering to
      shape the spectrum to be symmetric about the carrier frequency. We perform an
      experiment to verify the proposed method and obtain a 1.5 ps width in-phase pulse
      train from a 160 GHz beat signal. Furthermore, we employ a pulse compression
      scheme to reshape and compress the obtained pulse train, and we show that a 160
      GHz repeating, 0.7 ps FWHM, nearly transform-limited, in-phase sech pulse train
      is successfully generated.

PMID- 17546201
TI  - Calcium- and proton-dependent relocation of annexin A6 in Jurkat T cells
      stimulated for interleukin-2 secretion.
AB  - Annexin A6 (AnxA6) is a Ca(2+)-dependent membrane-binding protein involved in
      vesicular traffic. The likely participation of AnxA6 in the response of
      lymphocytes to Ca(2+) signals has not been investigated yet. The present study
      focuses on intracellular relocation of AnxA6 in human Jurkat T lymphoblasts upon
      stimulation followed by transient increase of intracellular [Ca(2+)] and
      exocytosis of interleukin-2 (IL-2). Stimulation of the cells under different
      experimental conditions (by lowering pH and/or by rising extracellular [Ca(2+)]
      in the presence of ionomycin) induced time-dependent transients of intracellular
      [Ca(2+)] and concomitant changes in AnxA6 intracellular localization and in IL-2
      secretion, with only minor effects on cell viability and apoptosis. In resting
      conditions (in the presence of EGTA or with no ionophore) AnxA6 was localized
      uniformly in the cytosol, whereas it translocated to vesicular structures beneath
      the plasma membrane within 5 min following stimulation of Jurkat T cells and rise
      of intracellular [Ca(2+)] at pH 7.4. Lowering the extracellular pH value from 7.4
      to 6.0 significantly enhanced this process. AnxA6 changed its location from the
      cytosol to the secretory granules and early endosomes which seem to represent
      membranous targets for annexin. In conclusion, AnxA6 is sensitive to variations
      in intracellular [Ca(2+)] upon stimulation of Jurkat T cells, as manifested by a
      switch in its intracellular localization from the cytosol to vesicular structures
      located in close proximity to the plasma membrane, suggestive of participation of
      AnxA6 in calcium- and proton-dependent secretion of cytokines by lymphocytes.

PMID- 17546202
TI  - Two-electron reduction of quinones by Enterobacter cloacae PB2 pentaerythritol
      tetranitrate reductase: quantitative structure-activity relationships.
AB  - In order to clarify the poorly understood mechanisms of two-electron reduction of
      quinones by flavoenzymes, we examined the quinone reductase reactions of a member
      of a structurally distinct old yellow enzyme family, Enterobacter cloacae PB2
      pentaerythritol tetranitrate reductase (PETNR). PETNR catalyzes two-electron
      reduction of quinones according to a 'ping-pong' scheme. A multiparameter
      analysis shows that the reactivity of quinones increases with an increase in
      their single-electron reduction potential and pK(a) of their semiquinones (a
      three-step (e(-),H(+),e(-)) hydride transfer scheme), or with an increase in
      their hydride-transfer potential (E(7)(H(-))) (a single-step (H(-)) hydride
      transfer scheme), and decreases with a decrease in their van der Waals volume.
      However, the pH-dependence of PETNR reactivity is more consistent with a single
      step hydride transfer. A comparison of X-ray data of PETNR, mammalian NAD(P)H :
      quinone oxidoreductase (NQO1), and Enterobacter cloacae nitroreductase, which
      reduce quinones in a two-electron way, and their reactivity revealed that PETNR
      is much less reactive, and much less sensitive to the quinone substrate steric
      effects than NQO1. This may be attributed to the lack of pi-pi stacking between
      quinone and the displaced aromatic amino acid in the active center, e.g., with
      Phe-178' in NQO1.

PMID- 17546203
TI  - Gamijeonssibaekchulsan regulates mast cell-mediated anaphylactic reaction.
AB  - Gamijeonssibaekchulsan (GJBS) is a typical Oriental medicine prescription which
      has been used in Korea for the treatment of allergic diseases and the development
      of physical strength. However, as yet there is no clear explanation of how GJBS
      affects the anaphylactic reaction and the immune function. In the present study
      murine models and MOLT-4 cells, a T cell line, were used to investigate these
      effects. Compound 48/80-induced systemic anaphylactic shock and ear swelling
      response were firstly analyzed. We also assayed histamine release and passive
      cutaneous anaphylaxis (PCA) in mice and cytokine productions in MOLT-4 cells.
      GJBS significantly inhibits compound 48/80-induced systemic anaphylactic shock
      and ear swelling response. GJBS also inhibits histamine release from rat
      peritoneal mast cells induced by compound 48/80. PCA activated by anti
      dinitrophenyl immunoglobulin E is attenuated by GJBS. However, GJBS dose not
      affect the production of interferon-gamma, interleukin (IL)-2, and IL-4 in MOLT-4
      cells. These results indicate that GJBS has a potential regulatory effect on
      allergic reactions that are mediated by mast cells.

PMID- 17546204
TI  - pVAX1 plasmid vector-mediated gene transfer of soluble TRAIL suppresses human
      hepatocellular carcinoma growth in nude mice.
AB  - The extracellular domain of the tumor necrosis factor-related apoptosis-inducing
      ligand (TRAIL) may function as a soluble cytokine to selectively kill various
      cancer cells without toxicity to most normal cells. We used a high-biosafety
      plasmid pVAX1 as a vector and constructed a recombinant plasmid expressing the
      extracellular domain (95-281 aa) of human TRAIL fused with signal peptides of
      human IgGgamma, designated as pVAX-sT. Transduction of human BEL7402 liver cancer
      cells with pVAX-sT led to high levels of sTRAIL protein in the cell culture media
      and induced apoptosis. The therapeutic potential of pVAX-sT was then evaluated in
      the BEL7402 transplanted naked mouse model. Subsequent intratumoral
      administration of naked pVAX-sT resulted in the expression of soluble TRAIL in
      the sera and the tumor site, as well as effective suppression of tumor growth,
      with no toxicity to liver. In conclusion, the successful inhibition of liver
      cancer growth and the absence of detectable toxicity suggest that pVAX-sT could
      be useful in the gene therapy of liver cancer.

PMID- 17546205
TI  - Electronic publishing and VCOT - A review.

PMID- 17546206
TI  - Acquired muscle contractures in the dog and cat. A review of the literature and
      case report.
AB  - Canine and feline muscle contracture is reported to affect several different
      muscles, is associated with a number of predisposing factors, and a varying
      prognosis depending upon which muscle is affected. Most patients suffer some form
      of trauma weeks to months before the contracture is present. The clinical signs
      include: lameness, pain, weakness, decreased range of motion, a firmness noted
      throughout the entire muscle, and usually a characteristic gait. Pre-disposing
      factors for muscle contracture include: compartment syndrome, infection, trauma,
      repetitive strains, fractures, infectious diseases, immune-mediated diseases,
      neoplasia, and ischaemia. There does appear to be some breed and age
      predilection, however, the sex of the animal does not have an appreciable
      influence. In general, muscle contractures of the forelimb respond better to
      treatment and carry a better prognosis than muscle contractures of the hindlimb.

PMID- 17546207
TI  - 3D kinematics of the equine metacarpophalangeal joint at walk and trot.
AB  - The metacarpophalangeal (MCP) joint and its supporting soft tissues are common
      sites of injury in athletic horses. Equine gait analysis has focused on 2D
      analysis in the sagittal plane and little information is available which
      describes 3D motions of the MCP joint and their possible role in the development
      of injuries. The aim was to characterize the 3D rotations of the equine MCP joint
      during walking and trotting. Three-dimensional trajectories of marker triads
      fixed rigidly to the third metacarpus and proximal phalanx of the right forelimb
      of healthy horses were recorded at walk (n = 4) and trot (n = 6) at 120 Hz using
      eight infra-red cameras. Kinematics of the MCP joint were calculated in terms of
      helical angles between the two segments using singular-value decomposition and
      spatial attitude methods. The ranges of motion were: flexion/extension: 62 +/- 7
      degrees at walk, 77 +/- 5 degrees at trot; adduction/abduction: 13 +/- 7 degrees
      at walk, 18 +/- 7 degrees at trot; and axial rotation: 6 +/- 3 degrees at walk, 9
      +/- 5 degrees at trot. Flexion/extension had a consistent pattern and amplitude
      in all horses and appeared to be coupled with adduction/abduction, such that
      stance phase extension was accompanied by abduction and swing phase flexion was
      accompanied by adduction. Axial rotation was small in amount and the direction
      varied between horses but was consistent within an individual for the two gaits.

PMID- 17546208
TI  - Evaluation of three approaches to meniscal release.
AB  - Three approaches to medial meniscal release (MMR) were compared using 48 canine
      cadaver stifles. The approaches included a caudomedial arthrotomy approach, a
      blind stab incision based on anatomic landmarks, and an arthroscopic guided
      approach. The cranial cruciate ligament was intact in all specimens. The time
      required to perform the meniscal release and joint capsule closure was recorded,
      as well as completeness and location of the meniscal transection. Damage to the
      caudal cruciate ligament, femoral cartilage, and medial collateral ligament were
      recorded. The mini-arthrotomy was 81% successful in accomplishment of MMR with a
      4% rate of iatrogenic damage. The blind technique was 56% successful in the
      accomplishment of MMR with a 4% rate of iatrogenic damage. The arthroscopic
      guided approach was 62.5% successful in accomplishment of MMR, with a 10% rate of
      iatrogenic damage. Accomplishment and iatrogenic damage rates were not
      significantly different among procedures (p > 0.05). Significantly less time was
      required to perform the blind technique, and significantly greater time was
      required to perform the arthroscopic guided technique (p > 0.05). Significant
      differences were not noted among the procedures regarding the ability to
      accomplish the meniscal release or damage surrounding structures. None of the
      evaluated approaches for meniscal release resulted in a complete and accurate
      meniscal release for over 81% of the time.

PMID- 17546209
TI  - Measurement differences between three versus five photocells during collection of
      ground reaction forces in dogs.
AB  - The differences between velocities and accelerations obtained from three and five
      photocells were examined when obtaining ground reaction force (GRF) data in dogs.
      Ground reaction force data was collected 259 times from 16 different dogs in two
      experimental phases. The first phase compared velocities and accelerations
      reported by the two systems based on trials accepted by the three photocell
      system. The second phase accepted trials based on data from five photocells.
      Three photocell data were calculated mathematically in the second phase in order
      to compare the values of both systems. The velocity and acceleration values
      obtained from each system were significantly different (at the hundredth of a
      meter per second). Differences in measured values did not result in acceptance of
      data by the three photocell system that would not have been acceptable with the
      five photocell system (false positives), but did result in rejection of
      acceptable data by the three photocell system (11% false negative rate). Given
      the small differences between the two systems, GRF data collected should not be
      significantly different, though the three photocell system is less efficient in
      gathering data due to the number of trials rejected as false negatives.

PMID- 17546210
TI  - Comparison of trot kinetics between dogs with stifle or hip arthrosis.
AB  - The purposes of this study were: 1) to describe and compare the trotting gait of
      normal and lame dogs secondary to stifle (GONOA) or hip (COXOA) osteoarthritis
      (OA) using multiple ground reaction forces (GRF) parameters, and 2) to pinpoint
      any characteristic in gait profile ('signatures') which could help to
      discriminate a lameness secondary to GONOA or COXOA. Fifty-one large breed dogs
      with OA (19 GONOA, 32 COXOA) and 22 normal dogs were included in the study. The
      vertical and cranio-caudal (braking-propelling) GRF were collected. The total
      stance time, and for each orthogonal vector, the peak force, impulse, time to
      peak, and the rate of limb loading were recorded. Vertical and craniocaudal
      forces were found to be significantly decreased in both OA groups compared to
      normal dogs. Vertical, cranial and caudal limb loading were also most often lower
      for both OA groups. In addition, the vertical and cranial forces were
      significantly lower in dogs with GONOA compared to COXOA and normal dogs. This
      study has demonstrated that, at a trotting gait, OA dogs secondary to GONOA and
      COXOA load their affected limb, brake and propel earlier during the stance phase,
      but generally with less magnitude than normal dogs. Dogs affected by GONOA also
      present more severe gait alterations than dogs with COXOA. The vertical and
      braking specific GRF alterations described may be kinetic 'signatures' linked
      more to lame dogs secondary to GONOA versus COXOA. Finally, this study has also
      provided useful baseline GRF data for further clinical and research
      investigations.

PMID- 17546211
TI  - The effect of measurement method on static weight distribution to all legs in
      dogs using the Quadruped Biofeedback System.
AB  - An application to measure static quadruped load distribution would be highly
      beneficial in the assessment of rehabilitation and lameness in many small animal
      patients. The scope of this study was to analyze the effects of confinement,
      location and local environment on the measurement of static quadruped load
      distribution as measured by the Quadruped Biofeedback System in normal dogs in
      order to better prescribe the use of this system. A prospective study of 20
      healthy adult dogs was performed to evaluate effects on measurement on quadruped
      load distribution. Data collection in the form of mean load per extremity was
      recorded four times in five positions for a total of 20 measurements for each
      limb. A replicated cross-over design in which a mixed effect, repeated measures
      analysis of variance was used to test for main effects of treatment and end as
      well as their interaction. The effects of right vs. left within each end and for
      each end was analyzed for each treatment and significance of p < 0.01 was
      established. Measurements were taken from 20 healthy adult dogs with no obvious
      lameness at the time of data collection. Analysis by end suggests that
      measurements were affected in similar manners in comparable locations. Each
      method demonstrated consistency in measurement without any significant influence
      by day or session, suggesting that one standardized method be established for
      measurement. With standardization, the Quadruped Biofeedback System has potential
      use as a reliable instrument for the measurement of quadruped load distribution
      in dogs.

PMID- 17546212
TI  - The effect of computed tomographical gantry angle on the measurement of the
      canine intercondylar notch.
AB  - This study was conducted to evaluate the clinical application of computed
      tomography of the canine femoral intercondylar notch. The canine femoral
      intercondylar notch is angled 12 degrees from the dorsal plane and obliqued 7
      degrees proximolateral to distomedial in the sagittal plane. Measurements of the
      notch were performed with eight, 12, and 16 degrees of gantry tilt. With the
      exception of proximal opening notch angle, significant differences were not
      detected in measurements referenced to 12 degrees of gantry tilt. Evidence from
      this study indicated that a +/- 4 degree variation in gantry tilt angle from a
      desired angle of 12 degrees did not significantly affect clinical interpretations
      of intercondylar notch measurements or notch width index ratios.

PMID- 17546213
TI  - Upward fixation of the patella in the horse. A retrospective study.
AB  - The objective of the present study was to assess the incidence of upward fixation
      of the patella (UFP) in different types of patients and to evaluate the outcome
      of conservative and surgical treatment for correcting this condition. A
      particular attempt was made to find out whether corrective trimming and/or
      shoeing (CTS) is efficient in the conservative treatment of UFP, and whether a
      longer postoperative resting period reduces the risk of complications after
      medial patellar desmotomy (MPD). Medical records of 78 horses with intermittent
      or permanent UFP were analyzed retrospectively. Young animals and ponies were
      mostly affected, mainly during winter (P < 0.05). Seventy-six horses with UFP
      were treated conservatively, with follow-up being possible in 64 of them. This
      treatment, in which CTS seemed the most important aspect, was fully successful in
      51.6% of these patients; 20.3% of them improved partially. In case of no response
      to conservative treatment, or in case of a permanent fixation, MPD was performed
      in 20 horses, which corrected UFP completely in 17 of the 18 followed-up
      patients. However, gait abnormalities were seen in seven of those 17 horses
      postsurgically, but with the incidence being lower in horses that had rested for
      at least three months (25%) compared to horses that had only rested for less than
      one month (66.6%). Results indicate that conservative treatment, with special
      attention for CTS, is worth trying before performing more radical procedures to
      correct UFP, and that a longer convalescence period after MPD is desirable.

PMID- 17546214
TI  - Carpal laxity syndrome in forty-three puppies.
AB  - Forty-three dogs with carpal laxity syndrome were included in the study. The
      cases were assessed with clinical and radiographical examinations. The case
      histories were obtained from patient owners. We recommended exercise and
      commercially available balanced diets for the treatment. In all cases, the
      clinical recovery period varied between one to four weeks. Healing occurred by
      the second week in the majority of cases (65.11%). The deformity was observed
      more frequently in male dogs (n = 30) than in female dogs (n = 13), and in six-
      to eight-week-old dogs. Carpal Laxity Syndrome is a more general term, used for
      both hyperextension and hyperflexion deformity. Malnutrition or over-nutrition of
      rapidly growing large breed puppies causes weakness and irregular tension between
      extensor and flexor muscle groups, which leads to laxity of the carpal joint.
      Exercise and commercially available balanced diets without any other treatment is
      usually enough to achieve physical and functional recovery.

PMID- 17546215
TI  - The use of an external skeletal traction device for distal fractures in the dog.
      A clinical case series of 11 patients.
AB  - Metacarpal and metatarsal fractures in 11 patients were treated 'closed' with a
      specially designed External Skeletal Fixation (ESF) frame with a walking bar and
      traction applied to the digits. Mediolateral angulation had improved
      postoperatively in 10 of the 11 patients. Craniocaudal angulation had improved in
      eight patients and could not be evaluated in three due to ESF frame
      superimposition. At follow-up, eight patients had a good clinical function,
      whereas three patients were still slightly lame. Only minor ESF-related
      complications were seen (pin loosening, pin tract infection, cerclage wire
      breakage and bending of the frame), which resolved without intervention after
      frame removal.

PMID- 17546216
TI  - Evaluation of clinical, radiographical and cytological findings compared to
      arthroscopic findings in shoulder joint lameness in the dog.
AB  - Forty-two dogs with lameness emanating from the shoulder joint were studied by
      clinical examination, radiographic examination, joint fluid analysis, and
      arthroscopic examination, following a set protocol. Dogs with mild clinical
      signs, absent or mild radiographic signs of osteoarthrosis, and without or with
      very mild changes in the synovial fluid, may still have moderate to severe
      degenerative pathological changes in the shoulder joint.

PMID- 17546217
TI  - Eosinophilic synovitis of the tarsocrural joint in a horse.
AB  - Eosinophilic synovitis (ES) is a rare disease described in human and veterinary
      medicine. Only three cases have been reported in the horse. A case of tarsocrural
      synovitis in an Hispano-Arabian gelding is presented in this report. The patient
      presented with severe joint effusion and lameness of the right tarsocrural joint
      on admission. Synovial fluid analysis revealed an increased WBC of 12800
      leukocytes/microliter with 76% of eosinophils. Lavage of the diseased joint and
      medical treatment with antibiotics and non-steroidal anti-inflammatory drugs
      produced remission of the clinical problem.

PMID- 17546218
TI  - Treatment of a shoulder luxation in a forelimb amputee dog.
AB  - An eight-year-old, male, thoracic limb amputee Whippet presented with a traumatic
      lateral luxation of the scapulohumeral joint. Surgical reduction and
      stabilisation of the shoulder joint by means of a modified Campbell
      scapulohumeral prosthesis and capsulorrhaphy was unsuccessful and reluxation of
      the shoulder joint occurred. Subsequent surgical stabilisation using bicipital
      tendon transposition and a modified Campbell scapulohumeral encircling prosthesis
      in combination with a novel body cast / Spica splint resulted in a return to
      satisfactory function of this limb.

PMID- 17546220
TI  - [Computational prediction of the tertiary structure of the human iduronate 2
      sulfate sulfatase].
AB  - INTRODUCTION: Hunter syndrome (MC KUSIK 309900) or mucopolysacharidosis type II
      is due to the deficiency of the enzyme iduronate 2 sulfate sulfatase (E.C.
      3.1.6.13). This enzyme has not been crystallized, and therefore the experimental
      structures are not available. OBJECTIVES: A computational three-dimensional model
      was proposed for the iduronate 2 sulfate sulfatase enzyme. MATERIALS AND METHODS:
      A computational analysis of this enzyme used the following free internet software
      programs: Comput pI/MW, JaMBW Chapter 3.1.7, SWISS-MODEL, Geno3d, ProSup. Energy
      minimization was done with Discover 3 and Insight II version 2004. RESULTS: A
      three-dimensional conformational model was proposed. The model showed 33.3% of
      helix structure, 7.2% beta sheet, and 59.5% random coil. RMS values (Root Mean
      Square) (0.78 and 0.86A) were found when compared with other enzymes of the same
      family. The model presented 5 exposed N-glycosylation potential sites and an
      entry to the pocket that contains the amino acids of the active site. A high
      correlation was found between the type of mutations and the severity of the
      phenotype in twenty patients analyzed. CONCLUSION: The RMS values, as well as the
      high correlation between the type of mutation and the phenotype, indicated that
      the model predicts some aspects of the enzymes biological behavior.

PMID- 17546221
TI  - [Subgingival microbiota in chronic and aggressive periodontitis in Bogota,
      Colombia: an epidemiological approach].
AB  - INTRODUCTION: Periodontitis-associated microbiotas differ in regions around the
      world and vary with a variety of factors. This suggests that each country must
      establish its own dental microbiobiotic profile in order to formulate adequate
      prevention measures and more specific treatments. OBJECTIVE: The prevalence and
      proportions of the following microorganisms were investigated: Porphyromonas
      gingivalis, Tannerella forsythia, Actinobacillus actinomycetemcomitans,
      Prevotella intermedia/Prevotella nigrescens, Eikenella corrodens, Campylobacter
      rectus, Micromonas micros, Fusobacterium spp, Dialister pneumosintes and enteric
      rods. The patients selected had been diagnosed with chronic periodontitis and
      aggressive periodontitis from clinical populations in Bogota, Colombia. The
      variables of age, gender and socioeconomic level were included in the
      comparisons. MATERIALS AND METHODS: 183 patients were classified in two groups,
      chronic periodontitis (n=84) and aggressive periodontitis (n=59); 40 healthy
      subjects were selected for comparison. A pooled subgingival plaque sample was
      obtained from the 6 deepest periodontal pockets in every patient and processed by
      culture for the isolation and identification of bacteria. RESULTS: In chronic
      periodontitis and aggressive periodontitis, P. gingivalis, T. forsythia, P.
      intermedia/P. nigrescens, C. rectus, Fusobacterium spp and E. corrodens showed
      high and similar prevalence, whereas M. micros, A. actinomycetemcomitans, D.
      pneumosintes and enteric rods (commonly from the tribe Klebsielleae) showed less
      and similar prevalence. In the healthy group, P. intermedia/P. nigrescens, C.
      rectus and Fusobacterium spp showed high frequency whereas M. micros and E.
      corrodens showed moderate frequency. CONCLUSIONS: Porphyromonas gingivalis, T.
      forsythia, P. intermedia/P. nigrescens, C. rectus, Fusobacterium spp. and E.
      corrodens are important constituents of the microbiologic profile of the
      periodontitis in Colombian populations. Porphyromonas gingivalis was found more
      frequently than A. actinomycetemcomitans in aggressive periodontitis.

PMID- 17546222
TI  - Genetic diversity of Giardia intestinalis populations in Colombia.
AB  - INTRODUCTION: Giardia intestinalis is a protozoan parasite that causes a
      gastrointestinal infection known as giardiosis, which is transmitted primarily
      through fecal-oral contamination. Genetic studies of axenically cultivated
      Giardia isolates have identified two major genetic groups distributed throughout
      the world. In the present study 24 native strains of the parasite were analyzed
      by the RAPD technique (Random Amplified Polymorphic DNA). OBJECTIVE: To determine
      the level of polymorphism and the complexity of Giardia intestinalis circulating
      strains in specific areas of Colombia. MATERIALS AND METHODS: The RAPD method was
      used, as it allows for a quick, simple and reliable analysis that requires no
      prior knowledge of the genetics of the parasite. A RAPD analysis was conducted on
      native isolates collected in Colombia between 1997 and 2001, established in
      continuous cultures. Several primers were tested separately, in order to enhance
      the capacity for discrimination of the method. RESULTS: Of the 24 strains that
      were included in the study, 22 were arranged in independent clusters. The strains
      that were from the same geographic area and collected at about the same time,
      generally displayed highly similar but distinguishable RAPD patterns. Clones
      isolated from a strain were analyzed as well, and it was possible to
      differentiate them molecularly. CONCLUSION: The studied strains showed to belong
      to genotype A . The results suggest that the Colombian strains studied consist of
      a heterogeneous mixture of closely related populations.

PMID- 17546223
TI  - [Diagnostic accuracy of five gestational references to predict insufficient birth
      weight].
AB  - INTRODUCTION: The maternal anthropometry is a potentially valuable tool in the
      evaluation of pregnancy status and prediction of birth weight. OBJECTIVES:
      Diagnostic accuracy of birth weight was compared for five gestational
      anthropometric references. MATERIALS AND METHODS: Longitudinal study was designed
      for 245 pregnant Colombian participants. Variables consisted of birth weight,
      gestational age, maternal height and weight. The references were as follows:
      gestational weight gain of Fescina (Uruguayan samples), % weight/height and body
      mass index of Rosso-Mardones (Chilean sample), pregestational weight of the
      Institute of Medicine (United States sample), and the body mass index of Atalah
      and colleagues (Chilean sample). The insufficient birth weight (<3,000 g) was
      defined as the critical threshold value. The following indices, with
      correspondent confidence intervals (CI 95%) were obtained: diagnostic accuracy,
      sensitivity, specificity, positive and negative predictive values, and agreement
      (Kappa index). RESULTS: The ability to predict the weight <3,000 g was higher in
      the first trimester measurement with the Chilean references, and in the second
      trimester with the USA and the Uruguayan references. The best concordance was
      presented between the Chilean references and the least with the Uruguayan. After
      the second trimester, the Chilean reference of Atalah and colleagues provided the
      best diagnostic accuracy, specificity and positive predictive value. CONCLUSION:
      The gestational anthropometric references that provided the most heterogeneous
      results were the US Institute of Medicine and the Fescina. Overall, the Atalah
      reference was the most accurate diagnostic predictor of insufficient weight at
      birth.

PMID- 17546224
TI  - [Polymorphisms of IL-10 gene promoter and rheumatoid arthritis in a Colombian
      population].
AB  - INTRODUCTION: Rheumatoid arthritis is an inflammatory disease driven by TH1 CD4+
      cells. Interleukin-10 is present in higher concentrations in serum and synovial
      fluid from patients with rheumatoid arthritis and has a marked anti-inflammatory
      activity. Furthermore, it is capable of stimulating B cells and increasing
      autoantibody production. Interleukin-10 synthesis is under genetic control.
      OBJECTIVE: Three polymorphisms of the promoter region were analyzed for
      interleukin-10 genes -1082, -819 and -592. Subjects were patients with rheumatoid
      arthritis compared with a control population for these genes. MATERIAL AND
      METHODS: One hundred two patients with rheumatoid arthritis and 102 matched
      healthy controls were studied. The following data were taken from the rheumatoid
      arthritis patients: age of disease onset, presence and titers of rheumatoid
      factor, and history of replacement joint surgery. Genotypes were obtained by
      polymerase chain reaction and sequence-specific primer method. The three
      polymorphisms are in strong linkage-disequilibrium and form three haplotypes 
      1082A/-819C/-592C, -1082A/-819T/-592A y -1082G/-819C/-592C. RESULTS: No
      association was detected between Interleukin-10 alleles, haplotypes/genotypes and
      rheumatoid arthritis. No significant differences occurred between interleukin-10
      polymorphisms and age of disease onset, presence and titer of rheumatoid factor
      and history of major joint replacement. CONCLUSIONS: Interleukin-10 is an
      important regulator of the immune response and likely plays a role in the
      pathogenesis of rheumatoid arthritis. The current results suggested that
      Interleukin-10 promoter polymorphisms were not important for development or
      severity of rheumatoid arthritis.

PMID- 17546225
TI  - [Adverse reactions by antibiotics in a pediatric and neonatal intensive care unit
      located in Bogota, Colombia].
AB  - INTRODUCTION: Critical care patients have a high probability of presenting
      adverse drugs reactions because the polytherapy that they receive usually include
      schemes with two or more antibiotics. Most antibiotics have high toxicity risk,
      which can be potentialized when being associated with other drugs. OBJECTIVE:
      Adverse reactions were detected and described in patients treated with
      antibiotics in a pediatric and neonatal intensive care. MATERIALS AND METHODS: A
      follow up, descriptive and observational study of a cohort was made without
      control group. A daily follow-up was administered for a three month period for
      each patient. Causality was evaluated on the basis of the Naranjo scale. RESULTS:
      Eighty-five patients were included in the study, 36.5% from the neonatal
      intensive care unit and 63.5% from the pediatric clinic. Of twenty-seven
      antimicrobial medications administered, 97 adverse reactions were detected for 15
      of these, in 37 patients (20 newborn and 17 older children). They were classified
      as mild (65%), moderate (35%) and serious (0). According to scale of Naranjo, 68%
      were possible, 32% probable, and defined, none. Based on laboratory test results,
      renal toxicity was detected in 38.1%, hematotoxicity in 24.7%,electrolytic
      abnormalities in 21.6% and hepatotoxicity in 15.5%. The distribution of adverse
      antibiotic reactions was as follows: gentamycine 20.6%, vancomycin 17.5%,
      amikacine 16.5%, ceftriaxone 15.5% and piperaciline tazobactam 13.4%.
      CONCLUSIONS: The proportion of adverse reactions was of 43.7%. 55.6% of
      antibiotics produced adverse reactions. A program of institutional
      pharmacovigilance coordinated by a medical pharmacologist or pharmaceutical
      chemist was recommended by these data.

PMID- 17546226
TI  - [Iron and vitamin A micronutrient status, risk factors for their deficiencies and
      anthropometric assessment in preschool child from Funza municipality, Colombia].
AB  - INTRODUCTION: The malnutrition and deficiencias of iron and vitamin A are
      frequent in the Colombian population and are associated with biological and
      environmental risk factors. OBJECTIVE: Prevalence of anemia, iron and vitamin A
      deficiencies and nutritional status was determined by anthropometric assessment
      in a population of preschool children in the municipality of Funza. Associations
      were made between micronutrient deficiency and other risk factors reported in the
      literature. MATERIALS AND METHODS: The nutrition status of 287 child preschool
      was assessed by means of anthropometric evaluation, levels of hemoglobin,
      ferritin, and vitamin A in blood sera, in addition to fecal examination. A survey
      was administered to identify risk factors associated with these deficiencies.
      RESULTS: Of these children, 40.8% showed anemia, 5.2% iron deficiency and 4.6%
      vitamin A deficiency. In addition, the children were generally malnourished.
      Significant associations were noted between low levels of hemoglobin, rented
      housing, lack of a nutritional program, low levels of vitamin A, and illness in
      the previous month. Nonsignificant, but statistical association was observed with
      other risk factors. CONCLUSION: Incentive programs are necessary to improve the
      nutritional situation of the preschool children from Funza municipality,
      Colombia. Nutritional status can be determined by examination of levels of folic
      acid, vitamin B12, iron and vitamin A in association with social risk factors.

PMID- 17546227
TI  - [Results of nine years of the clinical and epidemiological survey on
      cryptococcosis in Colombia, 1997-2005].
AB  - INTRODUCTION: A national survey on cryptococcosis has been conducted in Colombia
      since 1997. The survey data recorded over a 9-year period, 1997 to 2005, was
      summarized. MATERIALS AND METHODS: The format provided by the European
      Confederation of Medical Mycology was adapted with the correspondent permission.
      RESULTS: Over the 9 year period, 931 surveys were received from 76 centers. The
      associated disease syndromes were as follows: 891 (95.7%) were neurocryptococosis
      cases, 27 (2.9%) pulmonary disease, 5 (0.5%) cutaneous lesions, 2 (0.2%)
      ganglionar forms, 2 (0.2%) oropharyngeal lesions and one case (0.1%) each from
      peritonitis, liver lesion, cellulitis and urinary tract infection. Demographic
      data indicated 82.7% of the subjects were males, and 59.4% were between 20-39
      years old; 25 children less than 16 years old were reported. The prevalent risk
      factor was HIV infection (78.1%). The mean annual incidence rate of
      cryptococcosis in the general population was 2.4 X 106 inhabitants, but in AIDS
      patients the rate rose to one in 3 X 103. The most frequent clinical features
      were headache (85.2%), nausea and vomiting (59.1%), fever (59.0%), mental changes
      (46.2%), meningeal signs (33.4%), cough (23.6%) and visual alterations or loss of
      vision (20.9%). Laboratory data showed that direct examination of cerebrospinal
      fluid (CSF) was positive in 92.8% cases and Cryptococcus was recovered in 90.3%
      of the cases. Cryptococcal antigen reactivity was 98.9% in CSF and 93.7% in serum
      samples. From 788 isolates submitted, 95.9% were C. neoformans var. grubii
      serotype A, 0.3% var. neoformans serotype D, 3.3% C. gattii serotype B and 0.5%
      C. gattii serotype C. The majority of patients were treated initially with
      amphotericin B. CONCLUSION: Cryptococcosis incidence has increased dramatically
      in Colombia with the AIDS pandemic and it can be considered as a sentinel marker
      for HIV infection.

PMID- 17546228
TI  - [Antiinflammatory activity of extracts and fractions obtained from Physalis
      peruviana L. calyces].
AB  - INTRODUCTION: Cape gooseberry calyces (Physalis peruviana) have been used in folk
      medicine for their medicinal properties including anticancer, antimycobacterial,
      antipyretic, diuretic, immunomodulatory and antiinflammatory properties.
      OBJECTIVE: The antiinflammatory effect was evaluated for extracts and fractions
      obtained from Physalis peruviana calyces in a mice model of acute inflammation.
      The fractions responsible for antiinflammatory activity were extracted for
      possible identification. MATERIALS AND METHODS: The Physalis peruviana calyces
      were extracted by percolation with organic solvents. The primary hydroalcoholic
      fraction was purified by column chromatography. The antiinflammatory effect of
      extracts and fractions was evaluated using the 12-O-tetradecanoylphorbol-13
      acetate-induced mouse model of ear edema. RESULTS: Thirty-eight secondary
      fractions were obtained by column chromatography of primary hydroalcoholic
      fraction. Six fractions, evaluated in 12-O-tetradecanoylphorbol-13-acetate
      induced inflammation assay, showed significant antiinflammatory activity
      (p<0.05). The major fraction, Pp-D28-LF, showed a significant dose-dependent
      response at doses over 250 microg/ear. CONCLUSION: The antiinflammatory activity
      attributed to Physalis peruviana calyces was confirmed and validated its use in
      folk medicine. Fractions responsible for the antiinflammatory action were
      identified and seem promising for phytomedicinal development. Further studies are
      needed to isolate and identify the active constituents of these fractions as well
      as to ascertain the mechanisms involved in the antiinflammatory effect.

PMID- 17546229
TI  - [Mathematical models to correlate molecular topology with substrate affinity of
      the glycine antagonist in glutamate receptors].
AB  - INTRODUCTION: Mathematical models that correlate chemical structure with
      biological activity have been useful in the design of new drugs and can be used
      to predict biological behavior of new, chemically related molecules. OBJECTIVES:
      A mathematical model was generated to correlate the substrate affinities with
      variations in the molecular topology of glycine antagonists in NMDA sub-class
      glutamate receptor and, subsequently, to propose new molecules with antagonist
      activity. MATERIALS AND METHODS: By use of molecular connectivity indexes, the
      electronic structure and atomic bonding patterns of 45 glycine antagonists were
      coded. Correlation between connectivity indexes and antagonist affinity was
      determined by regression analysis. RESULTS: The connectivity index that best
      described affinity behavior was 4Xvpc, which indicates the relative importance of
      heteroatoms, the vicinity of aromatic ring substitutes, and valency gradient. The
      equations generated predicted new antagonist affinities, and the model was able
      to suggest structural requirements for designating compounds with increased
      affinity. Twelve new molecules were proposed, from which three appeared promising
      based of the affinities previously calculated by means of the new equations.
      Energetic interaction analysis was developed as a control for the mathematical
      methodology. CONCLUSION: Glycine antagonists structure were analyzed
      mathematically by means of connectivity indexes. The equations modeled receptor
      behavior and contributed useful information for new antagonist design.

PMID- 17546230
TI  - [Assessment of the efficacy of antimalarial drugs in Tarapaca, in the Colombian
      Amazon basin].
AB  - INTRODUCTION: The current antimalarial drug policy in Colombia has been based on
      studies conducted in Antioquia and the Pacific Coast. However, the efficacy of
      antimalarial drugs in other endemic regions is unknown. OBJECTIVE: The
      therapeutic efficacy of three monotherapies was assessed: amodiaquine and
      sulfadoxine/pyrimethamine for uncomplicated Plasmodium falciparum malaria, and
      chloroquine for Plasmodium vivax malaria in the municipality of Tarapaca, located
      in the Colombian province of Amazonas. MATERIALS AND METHODS: Treatment was
      supervised and clinical/parasitological follow-up was undertaken through a 28-day
      period following to World Health Organization standard protocols for subjects
      with a single P. falciparum or P. vivax infection. RESULTS: Due to a decrease in
      malaria transmission at the time of the study, the sample size was very small.
      The treatment failed for two subjects who received amodiaquine, and treatment
      with sulfadoxine/pyrimethamine was discontinued due to a high frequency of
      therapeutic failures (7/8). Most subjects (18/20) with P. vivax infections showed
      an adequate therapeutic response. CONCLUSIONS: The use of
      sulfadoxine/pyrimethamine in Tarapaca, and possibly in the Amazon region of
      Colombia, needs to be reviewed. Therapeutic efficacy studies in other endemic
      areas in the Amazon and Orinoco regions in Colombia are desirable but not
      feasible. Alternative methods such as in vitro assays or detection of molecular
      markers for resistance in the parasite can provide a basis for decisions
      concerning antimalarial drug policy for the Amazon and Orinoco regions in
      Colombia.

PMID- 17546231
TI  - Parental origin, nondisjunction, and recombination of the extra chromosome 21 in
      Down syndrome: a study in a sample of the Colombian population.
AB  - INTRODUCTION: Free trisomy 21 is responsible for 95% of Down syndrome cases.
      Advanced maternal age and susceptible recombination patterns are recognized risk
      factors associated to Down syndrome. Maternal origin of trisomy occurs in
      approximately 90% of cases; paternal and mitotic origin share the remaining 10%.
      However, the recombination events that serve as a risk factors for trisomy 21
      have not been carefully characterized. OBJECTIVE: To analyze and validate
      observations in a sample of Colombian trysonomy 21 cases. MATERIALS AND METHODS:
      Twenty-two Colombian families were selected, each with one affected Down syndrome
      (free trisomy 21) child. Microsatellite polymorphisms were used as DNA markers to
      determine the parental/stage origin of non-disjunction and recombination events.
      Non-parametric tests were used to compare our results with those reported.
      Multiple correspondence analysis was used to outline different groups and their
      associations. RESULTS: Distribution of trisomy 21 was 90.9% maternal, 4.5%
      paternal and 4.5% from mitotic origin, similar to distributions reported
      previously. However, we found differences in the frequency of maternal meiotic
      stage errors between the present study (46.1% meiosis I and 53.9% meiosis II)
      compared to those reported previously (70% meiosis I and 30% meiosis II).
      Multiple correspondence analyses showed association of either local recombination
      events or absence of recombination with specific non-disjunction stages.
      CONCLUSIONS: Recombination patterns found in this study support the hypothesis
      that susceptible chiasmate configurations are associated to maternal meiosis I
      and meiosis II errors. Non-disjunction frequencies between maternal meiotic
      stages need to be clarified in our population.

PMID- 17546233
TI  - [In Turner syndrome the thyroid function should not be forgotten].

PMID- 17546234
TI  - [Revising the stigmas of the thyroid in Turner Syndrome].

PMID- 17546235
TI  - [Mineralocorticoid resistance: pseudohypoaldosteronism type 1].
AB  - Pseudohypoaldosteronism type 1 (PHA1) is a rare genetic disease characterized by
      neonatal renal salt wasting, vomiting, dehydration and failure to thrive.
      Affected patients present hyponatremia, hyperkalemia, associated with high levels
      of plasma renin and aldosterone resulting from a renal or systemic resistance to
      aldosterone. The systemic form of PHA1 results in a severe phenotype, and high
      doses of salt supplementation are necessary. The symptoms are life-long
      recurrent. This form is associated with autosomal recessive transmission.
      Homozygous or compound heterozygous loss of function mutations in the genes
      coding for the epithelial sodium channel (ENaC) subunities are responsible for
      this disease. The renal form of PHA1 results in a mild phenotype. Low doses of
      salt supplementation are required and usually the symptoms remit at the end of
      the first year of life. Heterozygous loss-of-function mutations in the
      mineralocorticoid receptor (MR) gene are associated with the renal form of PHA1
      in the majority of the affected families but sporadic cases have been reported.
      In this review the mechanisms of aldosterone action and its effects are
      discussed. Additionally, clinical and molecular findings of a Brazilian family
      with the renal form of PHA1 caused by a nonsense mutation (R947X) in the MR gene
      are presented.

PMID- 17546236
TI  - [Effects of glycemic index on energy balance].
AB  - The prevalence of obesity has increased over the last decades. Associated to
      this, there has been observed a chance in the dietetic pattern of the population
      in general, related to the increase in carbohydrate consumption. According to
      some authors, the glycemic index (GI) of food may affect body composition and
      body weight. The purpose of this review was to evaluate the effects of GI on
      appetite, satiety, and body composition. Based on the scientific evidences
      reviewed, it was possible to verify that the majority of the studies that
      observed a positive effect of GI in that matter have a lot of methodological
      limitations. Well-designed studies have not observed any benefit of GI on these
      parameters. Therefore, it is concluded that GI has little application in clinical
      practice, as a useful tool to control satiety, reduce appetite, and consequently,
      to reduce the prevalence of obesity.

PMID- 17546237
TI  - [High-carbohydrate diets: effects on lipid metabolism, body adiposity and its
      association with physical activity and cardiovascular disease risk].
AB  - For many years the reduction in the dietary fat has been recommended to the
      population, in order to prevent cardiovascular diseases, obesity, type 2 diabetes
      mellitus, among other chronic diseases. The consequence has been the replacement
      of carbohydrates by fat, resulting in the adoption of high carbohydrate diets.
      However, it has been still discussed if very rich carbohydrate diets should be
      recommended to the general population. Researches point out controversies about
      the association between these dietary habits and harmful effects on health and
      metabolic aspects, such as raise in de novo lipogenesis and triglyceride
      concentration, reduction in HDL concentration and effects on adiposity. This
      review evaluates the effects of diet modification, particularly the high
      carbohydrate diet, in cardiovascular risk factors such as dyslipidemia and
      obesity. It also reviews its interaction with physical activity since it is still
      unknown with which extension it can minimize possible harmful effects of high
      carbohydrate diets in the long term.

PMID- 17546238
TI  - [Evidences for subclinic chronic autoimmune thyroid disease in girls with Turner
      Syndrome].
AB  - Patients with Turner syndrome (TS) frequently exhibit transient, recurrent and
      asymptomatic variations of TSH and/or thyroid hormones (TH). This work was
      carried out to evaluate thyroid function and structure in patients with TS who
      had had such variations in hormone concentrations. Our sample comprised 24
      patients, 17 less than 20-years old. Evaluation included serum levels of TSH,
      free T4, total T3, TPO and Tg autoantibodies, thyroid ultrasound (US) and
      scintigraphy with 99mTc-pertechnetate. Thirteen patients had abnormal TSH and/or
      TH levels; 23 exhibited US features compatible with chronic thyroid disorder,
      particularly thyromegaly (established according to volume expected for stature)
      and heterogeneous echogenicity. Uptake was normal in 21 cases and tracer
      distribution was homogeneous in 22. The finding of abnormal hormone
      concentrations was independent of age, length of time since the first similar
      finding, thyroid autoantibodies, number of abnormalities at US and abnormal
      scintigraphic findings. Patients aged more than 20 years had higher frequency of
      thyroid antibodies and heterogeneous echogenicity, and thyroid volume was
      significantly correlated to length of time since detection of the first hormone
      variation, indicating progressive thyroid disease. These results suggest that
      subclinical thyroid dysfunction in TS is due to chronic autoimmune thyroid
      disease.

PMID- 17546239
TI  - [Nephropathy and retinopathy in type 1 diabetics assisted by a universitary
      multiprofessional program].
AB  - Type 1 diabetes mellitus (DM) is linked to micro and macrovascular long-term
      complications. We proposed to study the association between diabetic nephropathy
      (DN) and retinopathy (DR), and of these complications with clinical-laboratory
      variables in type 1 DM patients followed in a universitary center. It was a
      transversal study through medical registry analysis. We studied 81 patients;
      prevalence of DR was 21.0% and of DN was 35.8%, there was association between the
      complications. Carriers of DN and DR have greater DM duration, greater
      hypertension prevalence, worse glycemic control and greater LDL cholesterol. It
      was found reduced glomerular filtration rate (GFR) in patients with microvascular
      complications, mainly in the ones with advanced lesions. In our study there was
      association between DR, ND and GFR, DM duration and hypertension were
      independently associated variables.

PMID- 17546240
TI  - [Diagnosis of metastases in patients with papillary thyroid cancer by the
      measurement of thyroglobulin in fine needle aspirate].
AB  - The widespread use of neck ultrasonography (US) during the follow-up of patients
      with papillary thyroid carcinoma (PTC) has led to the discovery of small cervical
      lymph nodes (LN). Although US has a high sensitivity for diagnosing LN, fine
      needle aspiration biopsy (FNA) and measurement of thyroglobulin in fine needle
      aspirates (FNA-Tg) have proven to be invaluable tools. The aim of this study is
      to determine the sensitivity of the combined use of neck US, FNA biopsy and FNA
      Tg for diagnosis of cervical lymph nodes. We have studied 32 patients with 44 LN
      detected by US, 19 classified as inflammatory and 25 as suspicious. 15 of those
      25 suspicious LN had high FNA-Tg (13 of the 15 had positive cytology and 2
      indeterminate). All of these 15 LN (11 patients) were proven to be PTC metastasis
      by histopathology. All 19 inflammatory LN and those 10/25 suspicious LN, had
      cytology negative for malignancy and undetectable FNA-Tg. We conclude that fine
      needle aspiration biopsy and FNA-Tg combined with neck US are essential for
      detecting positive cervical lymph nodes due to its high sensitivity and
      specificity and it should be considered the standard for investigating locally
      recurrent disease in patients with PTC.

PMID- 17546241
TI  - [Switching of NPH insulin to glargine therapy in a cohort of diabetic patients:
      observational study].
AB  - This study examined the impact of insulin glargine introduction in basal-bolus
      therapy in type 1 and type 2 diabetic patients with inadequate metabolic control
      (A1c > 6.9%) using previous NPH insulin regime. In this uncontrolled,
      retrospective study, 49 patients (28F/21M), average age 24.7 +/- 16.5, mean
      duration of DM 13.2 +/- 10.1 yrs., 93.1% DM1 patients, received insulin glargine
      plus mealtime rapid-acting insulin (lispro or aspart) followed by 90-day
      treatment. We analyzed mean total insulin dose, incidence of hypoglycemic events,
      convulsive crisis, hyperglycemic complications and A1c levels before and after
      three months of introduction of glargine therapy. A1c values were determined
      using the HPLC instrument, with a normal range of 4.3% to 6.9%. After switching
      to insulin glargine therapy, mean A1c dropped from 10.2 +/- 2.0 to 9.1 +/- 1.8%,
      with significant impact (p= 0.019). We observed a significant reduction of 0.11
      U/kg/day in total insulin dose, dropped from 0.75 U/kg of NPH to 0.64 U/kg of
      glargine, with significant correlation (p< 0.05). The introduction of glargine
      therapy was coincident with a decrease of hypoglycemic crisis (p= 0.02),
      convulsive events due to hypoglycemia (severe hypoglycemic crisis) (p= 0.023) and
      ketosis (p= 0.001) switching MDI-treated patients with improvement of metabolic
      control (reduction of A1c levels). This therapy improved quality of life in these
      patients due to a significant reduction of hypoglycemic (including severe)
      events, ketosis episodes and total daily insulin dose, with important impact on
      health public services.

PMID- 17546242
TI  - [Morphologic evaluation and Ca2+ mobilization by glicose and acetylcholine in
      human pancreatic cells].
AB  - AIMS: The proposal of this study was to analyze morphology of the organelles and
      cytoskeleton in human pancreatic cells cultured and the mobilization of the
      cytosolic calcium ([Ca2+]c) in response to glucose and ACh by fluorimetry method.
      MATERIAL AND METHODS: The cells were plated on glass coverslips, fixed and
      stained with a combination of fluorophores: the nuclei were stained with DAPI and
      mitochondria with Mytotracker Red. It was used phalloidin and the secondary
      antibodies Alexa Fluor conjugated green and red-fluorescent (488 and 594) to
      identify the protein cell actin F and type M3 muscarinic receptor respectively.
      The cells also were loaded with fura-2/AM to study Ca2+ mobilization. RESULTS:
      The human pancreatic cells show characteristics morphologically preserved with
      great amount of mitochondria. In region major cell density was evidenced pseudo
      islets and type M3 muscarinic receptors. Through increase of [Ca2+]c due to
      action of glucose and ACh were shown that the cells capacity to respond to these
      stimuli were conserved. The elevation of the [Ca2+]c depended on concentration by
      glucose-induced promoting sustained phase and ACh-induced a biphasic response.
      CONCLUSION: The morphologic characteristics of human pancreatic cells cultured
      were preserved. The Ca2+ mobilization in response to glucose and ACh confirmed
      its functionality. The expression of the M3 muscarinic receptors in human
      pancreatic cell cultured was demonstrated.

PMID- 17546243
TI  - [Prevalence of vitamin D deficiency, insufficiency and secondary
      hyperparathyroidism in the elderly inpatients and living in the community of the
      city of Sao Paulo, Brazil].
AB  - The occurrence of osteoporotic fractures in the elderly is associated with
      reduced levels of vitamin D and resulting secondary hyperparathyroidism, and
      inpatients are the ones at a higher risk. In Brazil, given its high level of
      insolation, the populations large amount of vitamin D is inferred to be adequate.
      In this study we aimed to assess the serum levels of 25-hydroxivitamin D (25OHD),
      parathormone (PTH) and ionized calcium (Cai), as well as to analyze the
      prevalence of both hypovitaminosis D and secondary hyperparathyroidism in the
      elderly living in the city of Sao Paulo. We studied 177 inpatients (125 women and
      52 men) with mean age (SD) 76.6 (9.0) years, and 243 outpatients (168 women and
      75 men) aged 79.1 (5.9) years. In this assessment 71.2% in the inpatients group
      and 43.8% in the outpatients group had 25OHD levels below the minimum recommended
      (50 nmol/l), with the women presenting with levels considerably lower than the
      men. Secondary hyperparathyroidism occurred in 61.7% of the inpatients and in 54%
      of the outpatients. Considering the results achieved, we recommend vitamin D
      supplementation in effective doses for the Brazilian elderly population, in
      addition to suggesting a discussion for the implementation of vitamin D-enhanced
      food policies, particularly oriented to the ones at a greater risk.

PMID- 17546244
TI  - [Waist measure and waist-to-hip ratio and identification of clinical conditions
      of cardiovascular risk: multicentric study in type 2 diabetes mellitus patients].
AB  - Abdominal obesity is associated with cardiovascular disease. This study aims to
      compare two measures of abdominal obesity [waist and wais-to-hip ratio (WHR)] in
      patients with DM2 to identify cardiovascular risk factors: ischemic cardiopathy,
      hypertension, dislipidemia, obesity and diabetic nephropathy. A multicentric
      study was performed in 820 patients with type 2 DM. Waist circumference strongly
      correlated with body mass index (BMI), for men (r= 0.814; P< 0.05) and women (r=
      0.770; P< 0.05). On the other hand, WRH was weakly correlated (r= 0.263, P< 0.05
      for men; r= 0.092, P< 0.05 for women). Only waist circumference correlated with
      systolic pressure (r= 0.211, P< 0.05 for men; r= 0,224, P< 0.05 for women). ROC
      curve analysis demonstrated the superiority of waist circumference measurement
      compared to WHR regarding obesity and hypertension for men and women, and
      dyslipidemia for men. In conclusion, waist circumference is better correlated
      with cardiovascular risk factor than WRH.

PMID- 17546245
TI  - [Phenotype variability in Noonan syndrome patients with and without PTPN11
      mutation].
AB  - INTRODUCTION: Around 50% of Noonan syndrome (NS) patients present heterozygous
      mutations in the PTPN11 gene. AIM: To evaluate the frequency of mutations in the
      PTPN11 in patients with NS, and perform phenotype-genotype correlation. PATIENTS:
      33 NS patients (23 males). METHODS: DNA was extracted from peripheral blood
      leukocytes, and all 15 PTPN11 exons were directly sequenced. RESULTS: Nine
      different missense mutations, including the novel P491H, were found in 16 of 33
      NS patients. The most frequently observed features in NS patients were
      posteriorly rotated ears with thick helix (85%), short stature (79%), webbed neck
      (77%) and cryptorchidism (60%) in boys. The mean height SDS was -2.7 +/- 1.2 and
      BMI SDS was -1 +/- 1.4. Patients with PTPN11 mutations presented a higher
      incidence of pulmonary stenosis than patients without mutations (38% vs. 6%, p<
      0.05). Patients with and without mutations did not present differences regarding
      height SDS, BMI SDS, frequency of thorax deformity, facial characteristics,
      cryptorchidism, mental retardation, learning disabilities, GH peak at stimulation
      test and IGF-1 or IGFBP-3 SDS. CONCLUSION: We identified missense mutations in
      48.5% of the NS patients. There was a positive correlation between the presence
      of PTPN11 mutations and pulmonary stenosis frequency in NS patients.

PMID- 17546246
TI  - [Low-dose aspirin in patients with diabete melitus: risks and benefits regarding
      macro and microvascular complications].
AB  - Aspirin is recommended as cardiovascular disease prevention in patients with
      diabetes mellitus. Due to the increased risk of bleeding and because of the
      hypothesis that there could be a worsening of microvascular complications related
      to aspirin, there has been observed an important underutilization of the drug.
      However, it is now known that aspirin is not associated with a deleterious effect
      on diabetic retinopathy and there is evidence indicating that it also does not
      affect renal function with usual doses (150 mg/d). On the other hand, higher
      doses may prove necessary, since recent data suggest that diabetic patients
      present the so called "aspirin resistance". The mechanisms of this resistance are
      not yet fully understood, being probably related to an abnormal intrinsic
      platelet activity. The employment of alternative antiplatelet strategies or the
      administration of higher aspirin doses (150-300 mg/d) should be better evaluated
      regarding effective cardiovascular disease prevention in diabetes as well as the
      possible effects on microvascular complications.

PMID- 17546247
TI  - Bone density and bone turnover markers in patients with epilepsy on chronic
      antiepileptic drug therapy.
AB  - In this comparative, cross-sectional study, we evaluated 55 patients with
      epilepsy on chronic use of antiepileptic drugs (AED); [(38 females and 17 males,
      35 +/- 6 years (25 to 47)] and compared to 24 healthy subjects (17 females/7
      males). Laboratorial evaluation of bone and mineral metabolism including
      measurements of bone specific alkaline phosphatase (BALP) and carboxyterminal
      telopeptide of type I collagen (CTX-I) were performed. Bone mineral density (BMD)
      was measured by DXA. BALP and CTX-I levels did not differ significantly between
      the groups. CTX-I levels were significantly higher in patients who were exposed
      to phenobarbital (P< 0.01) than those who were not. Patients presented BMD of
      both sites significantly lower than the controls (0.975 +/- 0.13 vs. 1.058 +/-
      0.1 g/cm(2); p= 0.03; 0.930 +/- 0.1 vs. 0.988 +/- 0.12 g/cm(2); p= 0.02,
      respectively). Total hip BMD (0.890 +/- 0.10 vs. 0.970 +/- 0.08 g/cm(2); p<
      0.003) and femoral neck (0.830 +/- 0.09 vs. 0.890 +/- 0.09 g/cm(2); p< 0.03) were
      significantly lower in patients who had been exposed to phenobarbital, in
      comparison to the non-phenobarbital users. In conclusion, patients on AED
      demonstrate reduced BMD. Among the AED, phenobarbital seems to be the main
      mediator of low BMD and increases in CTX-I.

PMID- 17546248
TI  - [Carotid intima-media thickness as a marker of cardiovascular risk in patients
      with subclinical hypothyroidism].
AB  - Subclinical hypothyroidism (SH) has been associated with an increased risk for
      coronary disease. Carotid intima-media thickness (IMT), as assessed by
      ultrasonography, is a precise marker of atherosclerotic changes and can be used
      as an endpoint for cardiovascular events. Aims of this study were to determine
      carotid IMT in a group of patients with SH and its possible association with an
      increase in cardiovascular risk. There were no significant differences in mean
      carotid IMT between patients and controls. Results of both groups were,
      respectively: common carotid arteries, 0.573 +/- 0.070 mm and 0.576 +/- 0.068 mm
      (p= 0.904); carotid bifurcation, 0.602 +/- 0.079 mm and 0.617 +/- 0.102 mm (p=
      0.714). Similar results were obtained when analyzing subgroups with serum TSH <
      or > 8 mIU/L and with positive or negative titers of TPOAb. The mean carotid IMT
      in these subgroups were: TSH 4-8 mIU/L: 0.579 +/- 0.070 mm and 0.586 +/- 0.063
      mm; TSH > 8 mIU/L: 0.569 +/- 0.073 mm and 0.616 +/- 0.091 mm; TPOAb+: 0.585 +/-
      0.070 mm and 0.621 +/- 0.085 mm; TPOAb-: 0.554 +/- 0.072 mm and 0.571 +/- 0.066
      mm. No differences in the lipid profile and in the apoprotein B and lipoprotein
      (a) levels between the groups were found. These findings suggest that mild SH
      with no related metabolic changes is not associated with an increase in
      cardiovascular risk, as assessed by carotid IMT.

PMID- 17546249
TI  - [Primary aldosteronism caused by aldosteronoma: problems in the etiologic
      diagnosis].
AB  - Primary aldosteronism (PA) represents an important cause of secondary
      hypertension, potentially curable, and it has been receiving particular attention
      due to its increasing prevalence, after the beginning of the use of plasma
      aldosterone concentration to plasma renin activity ratio as a screening method.
      We present a case of PA caused by an aldosteronoma associated with a
      contralateral nonfunctioning adrenal adenoma, which resulted in difficulties in
      the final diagnosis. We discuss the most appropriated tests to screen, confirm
      the diagnosis of PA and define the etiology of the disorder, especially the
      adrenal veins sampling to distinguish the aldosteronoma and idiopathic
      hyperaldosteronism and to guide successful treatment.

PMID- 17546250
TI  - [Diabetes mellitus associated with atypical antipsychotic medications: case
      report and review of the literature].
AB  - Since the introduction of atypical antipsychotic medications, starting with
      clozapine in 1990, many studies have associated these drugs with the development
      of diabetes among other metabolic disorders, as well as with the onset of the
      disease as ketoacidosis. We report the case of a 28-year-old patient with
      schizophrenia who was admitted with diabetic acidosis 1 month after the beginning
      of clozapine therapy. No weight gain was reported and the patient maintains
      satisfactory glycemia levels with no treatment required after discontinuation of
      the drug. The literature on this subject and cases reported so far are reviewed,
      including the association of other atypical antipsychotic drugs also involved in
      endocrine disorders. The objective of this report is to raise the awareness of
      physicians treating psychiatric patients to the possibility of new-onset diabetes
      during therapy with atypical antipsychotic drugs and to emphasize the necessity
      for increased vigilance and close metabolic follow-up of these patients.

PMID- 17546251
TI  - [Discrepancy between IGF-1 and GH during 75 g oral glucose tolerance test
      measures to acromegaly screening in a patient with macroprolactinoma--case report
      and literature review].
AB  - We describe a patient with macroprolactinoma and discrepant insulin-like growth
      factor (IGF-1) concentration (elevated) and growth hormone (GH) values during a
      75 g oral glucose tolerance test (normal), that were measured to evaluate the co
      secretion of GH by tumor. With the bromocriptin use, the patient achieved
      normalization of prolactin, but persisted with high levels of IGF1, suggesting to
      be subclinical acromegaly. After the development of new more sensitive GH assays,
      cases of discrepant GH and IGF-1 results have been observed and taken to some
      authors to suggest that GH nadir concentration during 75 g OGTT used to
      acromegaly diagnosis and treatment could be lower than values considered
      currently normal. Thus, if this is confirmed, subclinical and oligosymptomatic
      acromegaly cases could have earlier diagnoses.

PMID- 17546252
TI  - [High intake of phytoestrogens and precocious thelarche: case report with a
      possible correlation].
AB  - Precocious thelarche is the breast development before 8 years of age with two
      peaks of incidence during the first two years of life and after 6 years of age. A
      4.75-year-old girl presented with thelarche associated to an excessive intake of
      phytoestrogens (phye). Tanner development B2P1-2, hormonal levels and pelvic US
      were compatible with peripheral precocious puberty. During follow-up, a daily
      intake of soy-based foods was observed (> 40 mg phye/day). Soy is rich in
      phytoestrogens, mainly genistein and daidzein. Although phye are less strong than
      estradiol, its concentration could be from 13,000 to 22,000 times stronger in
      children fed only by soy-based formulas. Parents were advised and soy intake was
      reduced to once a week. Progression of pubertal development ceased at B2-3P1. The
      patient, now 8.66 years old, keeps growing with similar bone and chronological
      ages. Some questions related to industrial food security, mainly the soy-based
      food, remain without precise answer. Although it is well known the entity of non
      progressive precocious puberty and premature thelarche, pubertal development in
      this case was strongly related to excessive daily intake of soy and other phye
      rich food that could trigger puberty as endocrine disruptor.

PMID- 17546253
TI  - Cross-reactivity of new insulin analogs in insulin assays.

PMID- 17546254
TI  - Multi-arterial myocardial bridge: uncommon clinical and anatomical presentations.
AB  - We report the case of a 42-year-old man with no risk factors for coronary artery
      disease admitted with atypical chest pain. The electrocardiogram performed after
      intravenous injection of nitrate revealed ST-segment elevation in leads V1 to V4.
      The coronary angiography showed myocardial bridges in the three coronary
      arteries, besides an unusual length of the left anterior descending artery (80
      mm). The patient progressed well following the discontinuation of nitrate use and
      introduction of beta-blockers and calcium channel antagonists.

PMID- 17546255
TI  - Coronary artery bypass surgery in patients with anomalous circumflex artery.
AB  - The anomalous origin of the circumflex artery (Cx) is uncommon and presents
      course variations that might make the coronary artery bypass surgery (CABG)
      difficult. Two patients presenting unstable angina were submitted to coronary
      angiography that disclosed tri-vessel disease and presence of Cx with an
      anomalous origin and retroaortic course with severe stenosis. Both patients
      underwent CABG with use of bilateral internal thoracic artery (ITA) grafts.
      Therefore, CABG with bilateral ITA use is feasible in cases of an anomalous
      origin of the Cx artery. However, this finding may constitute an additional
      technical setback.

PMID- 17546256
TI  - Eustachian valve endocarditis.
AB  - Eustachian valve endocarditis is a rare condition that affects mostly injectable
      drug users and patients using pacemakers or central venous catheter. We describe
      the case of a patient who underwent myocardial revascularization with
      extracorporeal circulation and who presented Eustachian valve endocarditis in the
      postoperative period, diagnosed by echocardiogram. The blood culture identified
      Klebsiella pneumoniae. He received appropriate antibiotic therapy and presented
      resolution of the condition within four weeks.

PMID- 17546257
TI  - Infracardiac total anomalous pulmonary venous drainage: a diagnostic challenge.
AB  - Infracardiac total anomalous pulmonary venous drainage can be erroneously
      diagnosed as respiratory distress of several different etiologies during the
      neonatal period. A cross-sectional echocardiography study with Doppler color flow
      mapping can preoperatively determine the precise drainage site and pulmonary
      venous return pattern, thereby allowing cardiac surgery to be performed promptly,
      prior to any clinical deterioration.

PMID- 17546258
TI  - Coronary giant cell arteritis and acute myocardial infarction.
AB  - Giant cell arteritis (GCA) is a systemic immune-mediated granulomatous vasculitis
      of large- and medium-sized arteries mainly affecting elderly people. Death from
      GCA alone is rare and usually results of ruptured aorta. In this paper is
      reported a case of a 83-year-old woman who unexpectedly died during treatment of
      GCA. Necropsy revealed inflammatory involvement of the coronary arteries with
      left descendent anterior artery thrombosis, myocardial infarct and rupture of the
      anterior wall of the left ventricle, as well as hemopericardium and cardiac
      tamponade. Myocardial infarction leading to sudden death is an exceptional
      complication of GCA.

PMID- 17546259
TI  - Health profiles--Brazil 2006--changes and their causes.

PMID- 17546260
TI  - Surgical treatment of patients with heart failure through myocardial
      revascularization, ventricular reconstruction, and mitral valve surgery.

PMID- 17546261
TI  - Left atrial appendage: real-time three-dimensional transthoracic
      echocardiographic image.

PMID- 17546262
TI  - I(f) current and heart rate control.

PMID- 17546263
TI  - Economic analysis of drug-eluting coronary stents in Brazil: a choice for all or
      just for a few patients?

PMID- 17546264
TI  - Evaluating cardiac vagal activity on a conventional electrocardiogram.
AB  - OBJECTIVE: To determine the viability of using a conventional electrocardiogram
      (ECG) tracing for assessment of CVA. METHODS: We retrospectively analyzed 1395
      individuals (995 males), aged 46 +/- 17.2 years (mean +/- standard deviation)
      with conventional ECG tracings to measure the delta RR (which represents the
      difference in milliseconds (ms) between the greatest and smallest RR interval)
      and results of a second autonomic parasympathetic evaluation, the 4-second
      exercise test (T4s), that quantifies CVA by the cardiac vagal index (CVI). ROC
      curves were obtained to determine the values of Delta RR for a closer correlation
      with sensitivity and specificity for 1.20 and 1.95 ms, the low and high CVA
      cutoff points, respectively. RESULTS: The delta RR levels correlated
      significantly with those of the CVI (r=0.40; p<0.001). We identified < or = 60
      and > or = 120 ms as the best cutoff points for low and high CVA. Sensitivity was
      75% and 57%, specificity was 62% and 79%, and the areas of the ROC curves were
      0.76 and 0.74, respectively. CONCLUSION: The visual measurement of delta RR on an
      ECG tracing seems to be a valid quick preliminary clinical evaluation of CVA and
      can be useful in medical offices, emergency units, or situations in which the use
      of more sophisticated methods may not be feasible, appropriate, or convenient.

PMID- 17546265
TI  - Effectiveness of the Amplatzer device for transcatheter closure of an ostium
      secundum atrial septal defect.
AB  - OBJECTIVE: To evaluate the effectiveness of the Amplatzer septal occluder in the
      treatment of ostium secundum atrial septal defects (OS ASDs). METHODS:
      Retrospective cohort study conducted between November 1998 and September 2005
      involving 101 OS ASD transcatheter occlusion procedures in our institution. All
      procedures were conducted in the hemodynamic laboratory under general anesthesia
      with transoesophageal echocardiographic monitoring (TEE). Clinical and
      echocardiography assessments of the patients were conducted at 30 days, six
      months and on an annual basis. The results are presented as averages, standard
      deviations and percentages. Event-free survival was estimated using the Kaplan
      Meier curve. RESULTS: From the 101 patients, 60 (59.4%) were females. Mean age,
      weight, height, body mass index and body surface area were, respectively: 24.3 +/
      18.31 years, 51.88 +/- 23.76 kg, 140.59 +/- 39.3 cm, 23.18 +/- 18.9 kg/m(2) and
      1.24 +/- 0.21 m(2). The prevalence of interatrial septum aneurysms was 4.95%, and
      98 cases had an isolated defect. ASD diameters were 21.47 +/- 6.96 mm using an
      angiography and 21.22 +/- 7.93 mm using a TEE. The average size of the implanted
      devices was 23.92 +/- 7.25 mm, ranging from 9 mm to 40 mm. The procedure time was
      90.47 +/- 26.67 minutes and the average hospital stay was 2.51 +/- 0.62 days.
      Clinical and echocardiography follow-up was conducted at 12.81 +/- 8.41 months
      and all devices were securely anchored without any residual shunts. The procedure
      success rate was 93% (94/101). In five cases adequate deployment of the device
      was not possible and 2 patients presented residual ASD. No major complications
      occurred. CONCLUSION: The Amplatzer septal occluder is an effective OS ASD
      transcatheter treatment device.

PMID- 17546266
TI  - Randomized comparative study of diamond-like carbon coated stainless steel stent
      versus uncoated stent implantation in patients with coronary artery disease.
AB  - OBJECTIVE: To compare restenosis and major cardiac event rates at one and six
      months after DLC-coated stent implantation with those of uncoated stents.
      METHODS: Randomized, prospective, comparative study of 180 patients with coronary
      insufficiency undergoing DLC coated stent (Phytis) or uncoated stent (Penta)
      implantation, from January, 2003 to July, 2004. Inclusion criteria were: de novo
      lesion with >50% diameter stenosis in a coronary artery with reference diameter >
      or = 2.5 mm and < or = 4 mm, and length < 20 mm. Exclusion criteria were: left
      main coronary artery and bifurcation lesions, chronic total occlusion, and in
      stent restenosis. RESULTS: Clinical and angiographic baseline characteristics of
      the groups were similar. Procedural success was achieved in 98.9% of the patients
      in both groups. One cardiac death occurred in each group during hospitalization.
      Reference diameter and acute gain were greater in the Penta group (3.21 +/- 0.37
      mm vs. 3.34 +/- 0.8 mm, p=0.02 and 2.3 +/- 0.5 vs. 2.49 +/- 0.5, p=0.009,
      respectively). Angiographic follow-up at six months showed similar rates of
      restenosis (24.3% vs. 21.8%, p=0.84) and of major cardiac events (16.8% vs.
      17.5%, p=1). CONCLUSION: DLC coated stents did not provide better outcomes in
      relation to uncoated stents.

PMID- 17546267
TI  - Echocardiograph pulmonary venous flow patterns in congenital heart defects with
      increased pulmonary flow.
AB  - OBJECTIVES: To describe pulmonary venous flow patterns using transthoracic
      echocardiograms on children suffering from different congenital heart defects
      with increased pulmonary flow. METHODS: Prospective study and consecutive
      selection of children suffering from congenital heart defects with increased
      pulmonary flow. The transthoracic, apical view, Doppler echocardiogram was used,
      positioning the sample-volume at the lower pulmonary vein, 4mm from its junction
      with the left atrium. The data analyzed included: dominant systolic or diastolic
      pulmonary venous flow and atrial contraction waveform characteristics, designated
      as "A" for absent and "R" for reversed. RESULTS: The study included twenty-nine
      patients with a mean age of 29.9 +/- 58.9 months, suffering from the following
      congenital heart conditions: interatrial and interventricular communication
      defects, patent ductus arteriosus, atrioventricular septal defects, total
      transposition of the great arteries and truncus arteriosus. All the patients
      presented a continuous pattern of high velocity pulmonary venous flow. Nine
      patients presented a dominant systolic waveform (31%), eighteen presented a
      dominant diastolic wave form (62%) and 2 patients had systolic and diastolic wave
      forms of equal amplitude (7%). Six patients (21%) presented a R atrial
      contraction waveform and 23 (79%) presented an A atrial contraction waveform.
      CONCLUSION: Congenital heart diseases with increased pulmonary flow present a
      continuous pattern of high velocity pulmonary venous flow with alterations mainly
      in the atrial contraction reversal pattern.

PMID- 17546268
TI  - Aortopulmonary window--impact of associated lesions on surgical results.
AB  - OBJECTIVES: The aortopulmonary window (APW) is a communication between the
      pulmonary artery (PA) and the ascending aorta in the presence of two separate
      semilunar valves. This review describes the natural history of the APW and the
      impact of associated defects on surgical results in patients treated at our
      institution. METHODS: Retrospective longitudinal study, based on the review of
      medical files of patients diagnosed between 1995 and 2005. RESULTS: Of nine
      patients diagnosed as having APW, six had associated lesions. Seven patients were
      submitted to surgical treatment with two deaths. One patient was not submitted to
      surgery due to pulmonary hypertension and another one died before the surgery due
      to a respiratory infection complication. CONCLUSION: The surgical results are
      satisfactory when the APW presents as an isolated defect and when surgery is
      performed early, preventing the development of irreversible arterial pulmonary
      hypertension (APH). The presence of associated complex congenital heart disease
      is a bad prognostic factor in our series.

PMID- 17546269
TI  - Correction of simple congenital heart defects in children and adolescents through
      minithoracotomies.
AB  - OBJECTIVE: To evaluate the repair of congenital heart defects through
      minithoracotomies. METHODS: Between January 1998 and March 2005, 98 patients
      underwent minithoracotomies for simple congenital heart defect repairs at our
      institution. All patients were female between the ages of 14 months and 16 years
      (mean 4.6) with weights ranging from 8 to 58 Kg (mean 20). Diagnoses included 78
      cases of atrial septal defects (ASD) (six with associated partial anomalous
      pulmonary venous drainage and four with pulmonary valve stenosis) and 20 cases of
      perimembranous ventricular septal defects (PVSD). All diagnoses were confirmed
      with an echocardiogram; therefore, cardiac catheterization was not required. A
      right submammary minithoracotomy was performed on 10 patients and a
      minithoracotomy with a partial median sternotomy was performed on 88 patients.
      RESULTS: All defects were corrected successfully with satisfactory exposure.
      Cardiopulmonary bypass times ranged from 8 to 30 min (mean 10) and aortic
      clamping times ranged from 5 to 22 min (mean 12). All patients were extubated in
      the operating room and hospital stays ranged from 3 to 7 days (mean 5). There
      were no deaths during the operation or severe postoperative complications. No
      residual shunts were observed. CONCLUSION: Our study demonstrated that the
      minithoracotomy is a safe effective and technically viable alternative to a
      median sternotomy to correct selected simple congenital heart defects. The
      advantages of this approach include less trauma, partial or complete preservation
      of sternum continuity and integrity, and elimination of postoperative deformities
      such as pectus carinatum. The cosmetic outcome was superior to a median
      sternotomy.

PMID- 17546270
TI  - Metabolic syndrome in patients undergoing coronary artery bypass graft:
      prevalence and a marker of morbidity/mortality during hospitalization and 30 days
      after hospital discharge.
AB  - OBJECTIVES: To compare the morbidity and mortality of patients with and without
      metabolic syndrome (MS) (according to the First Brazilian Guidelines for
      Diagnosis and Treatment of MS) undergoing coronary artery bypass graft (CABG)
      during hospitalization and after 30 days. METHODS: A total of 107 patients who
      underwent CABG with no associated procedures were assessed between August and
      October 2005; 74 (69.2%) of them had MS. Criteria of in-hospital outcome were:
      acute atrial fibrillation (AF), prolonged mechanical ventilation (MV), need for
      transfusion of blood products, number of hours spent in the ICU, length of
      hospital stay (days), respiratory and surgical wound infection, and death. For 30
      days, the combination of events such as the need for readmission to hospital,
      surgical wound infection and death was assessed. RESULTS: The mean age was 60.6
      +/- 9.7 years, and the group with MS presented a higher body mass index and body
      surface, and a higher prevalence of diabetes. No statistically significant
      difference was observed in the occurrence of in-hospital events such as AF (15.2%
      vs. 16.2%), MV (3.0% vs. 2.7%), number of units of blood products used (3.2 +/-
      2.7 vs. 2.6 +/- 2.9), length of ICU stay (53.7 +/- 27.3 vs. 58.9 +/- 56.5),
      length of hospital stay (9.2 +/- 8.7 x 8.5 +/- 8.5), respiratory infection (6.1%
      vs. 2.7%), surgical wound infection (3.0% vs. 5.4%), and mortality rate (3.0% vs.
      0.0%). The occurrence of combined events in 30 days was similar in both groups
      (12.2% vs. 20.3%, p = NS). CONCLUSION: Patients with MS did not have increased
      morbidity and mortality when undergoing CABG, however they had a higher trend of
      occurrence of surgical wound infection.

PMID- 17546271
TI  - Hospital costs of coronary artery bypass grafting on elective coronary patients.
AB  - OBJECTIVE: To assess hospital costs associated with coronary artery bypass
      grafting performed on elective coronary patients, and the relation of costs with
      the number of grafts. METHODS: Descriptive prospective study carried out at
      Instituto Dante Pazzanese de Cardiologia in April, May and June of 2005. Coronary
      patients of different ages and both genders were included. Emergency patients,
      patients with other associated heart conditions and reoperation cases were
      excluded. Appropriate forms for the operating room, early postoperative period
      and for the final period in the ward were developed for the initial
      hospitalization phase preoperatively. RESULTS: The procedure was performed on 103
      patients, at an average cost of R$6,990.00 (US$2,784.98), at a minimum of
      R$5,438.69 (US$2,166.81), and maximum of R$11,778.96 (US$4,692.81); standard
      deviation was R$1,035.47 (US$412.54) and the confidence interval was 95%, ranging
      from R$6,790.33-R$7,190.27 (US$2,705.31-US$2,864.67). The total average cost for
      three to five bypass grafts was higher (R$7,148.05) than for one and two bypass
      grafts (R$6,659.29) and the difference was significant (p < 0.05). CONCLUSION:
      The highest average costs were in the operating room (R$4,627.97), and in the
      early postoperative period (R$1,221.39), followed by costs incurred in the ward
      after the early postoperative period (R$840.04) and by the initial preoperative
      period in the ward (R$300.90).

PMID- 17546272
TI  - Total plasmatic homocysteine and von Willebrand factor in experimental diabetes
      mellitus.
AB  - OBJECTIVES: To determine the plasma homocysteine and von Willebrand factor levels
      as markers of endothelial dysfunction in rats with diabetes mellitus induced by
      streptozotocin. METHODS: Thirty-five adult male rats (Rattus norvegicus albinus)
      (weight between 180-200 g) were randomized into three groups: control group
      (n=10), which received no drugs or vehicles; sham group (n=10), which received
      streptozotocin solution; and diabetic group (n=15), which received
      streptozotocin. Eight weeks after diabetes mellitus induction, the animals were
      weighed and anesthesized; blood samples were collected from abdominal aorta for
      plasma total homocysteine, von Willebrand factor and glucose levels. RESULTS: The
      experimental model was reproducible in 100% of animals. The mean plasma
      homocysteine levels were: 7.9 micromol/l (control), 8.6 micromol/l (sham) and 6.1
      micromol/l (diabetic), with difference among the groups (p<0.01). Multiple
      comparison analysis among the groups showed that values in the diabetic group
      were lower than in the sham group (p<0.01). The mean von Willebrand factor values
      were 0.15 U/l (control), 0.16 U/l (sham) and 0.18 U/l (diabetic), with difference
      among the groups (p=0.03). The mean value was higher in the diabetic group than
      in the control group (p<0.05). Correlation between homocysteine and von
      Willebrand factor was not observed in the diabetic group. CONCLUSION: Reduced
      homocysteine levels and increased von Willebrand factor levels were observed in
      diabetes mellitus induced by streptozotocin; nevertheless, there were no
      correlations between them and with final glucose levels.

PMID- 17546273
TI  - Serum ferritin and obstructive coronary artery disease: angiographic correlation.
AB  - OBJECTIVE: To verify the possible association between the levels of serum
      ferritin and the degree of obstructive coronary artery disease. METHODS: 115
      patients with coronary arteriography and concomitant evaluation of serum ferritin
      were studied. The adopted cut-off values were 80 ng/ml for women and 120 ng/ml
      for men. RESULTS: The mean ferritin levels for males and females were 133.9 +/-
      133.8 ng/ml and 214.6 +/- 217.2 ng/ml, respectively (p=0.047). It was observed
      that 44.1% of the women had normal serum ferritin levels in comparison to 30.9%
      of the men (p=0.254). In the patients without obstructive coronary artery disease
      or with less severe obstructions (group A) the serum ferritin level was 222.3 +/-
      325 ng/ml. On the other hand, for those with moderate (group B) and severe
      obstructions (group C) the levels were 145.6+-83.7 ng/ml and 188.9 +/- 150.6
      ng/ml, respectively. There was no correlation between the degree of coronary
      artery disease and the mean level of serum ferritin. Regarding the cut-off value,
      the number of women with serum ferritin level > 80 ng/ml in groups B+C or only C
      was significantly higher than the number of women in group A (ODDS RATIO 9.71
      with 95%CI from 1.63 to 57.72). For males there was no significant difference
      between the number of cases above or below the cut-off values (ODDS RATIO 0.92
      with 95%CI from 0.28 to 2.95). CONCLUSION: It was verified that women with serum
      ferritin levels > 80 ng/mL presented more severe obstructive coronary artery
      disease than women with lower levels. In men, the serum ferritin level was not a
      predictor element of the degree of obstruction.

PMID- 17546274
TI  - Effectiveness of sustained-release bupropion in the treatment of smoker patients
      with cardiovascular disease.
AB  - OBJECTIVES: To evaluate the effectiveness of and tolerability to sustained
      release bupropion, in smokers with cardiovascular diseases treated in a smoking
      cessation service, as well as to investigate variables predictive of success or
      failure in smoking cessation. METHODS: Sustained-release bupropion was prescribed
      to 100 current smokers with cardiovascular disease for 12 weeks. Patients were
      followed for 52 week. The variables studied were gender, age, number of
      cigarettes, exhaled carbon monoxide, nicotine dependence (Fagerstrom Tolerance
      Questionnaire), depression (Beck Depression Inventory), anxiety (State-Trait
      Anxiety Inventory), alcohol consumption (Alcohol Use Disorders Identification
      Test), number of diagnoses other than smoking, adverse events, and use of
      medications concomitantly with sustained-release bupropion. RESULTS: Abstinence
      rate was 50% at week 12 and 25% at week 52. The logistic regression analysis
      showed that ageing was positively associated with success, whereas the worsening
      of the condition, as verified by the presence of a higher number of other health
      conditions associated with smoking, was negatively associated with success.
      CONCLUSION: We conclude that the prescription of bupropion for smokers with
      cardiovascular diseases proved to be safe and effective, especially during the
      treatment period (week 12).

PMID- 17546275
TI  - A study on systemic arterial hypertension in Campo Grande, MS, Brazil.
AB  - OBJECTIVES: To detect the actual prevalence of systemic hypertension in the city
      of Campo Grande, MS, Brazil, and frequent factors. METHODS: Cross-sectional study
      with a randomized sample of the adult population of the city of Campo Grande, MS,
      in a total of 892 individuals. A questionnaire on age, gender, level of
      education, smoking, alcohol consumption, and aspects of the treatment was
      applied. Anthropometric data (weight and height) were collected. According to the
      WHO, a BMI<25 kg/m2 was considered normal weight; 25>BMI<30 overweight; and BMI>
      30 obesity. Criteria for hypertension were based on the JNC VII report, with
      blood pressure cut-off values of 140 x 90 mmHg. RESULTS: The prevalence of
      hypertension was 41.4%, varying with age (up to 29 years: 11.8%; 30-39: 24.8%; 40
      49: 43.3%; 50-59: 42.4%; 60-69: 48.6% and > 70: 62.3%). A higher prevalence was
      observed among men (51.8%), whereas among women the prevalence was 33.1%.
      Individuals with basic level of education tended to present higher rates. Among
      overweight and obese individuals, a higher prevalence of hypertension was
      observed: normal BMI (27.9%), overweight (45.6%) and obesity (58.6%). Above 60
      years of age, a higher percentage of isolated systolic hypertension was observed,
      with 16.4% (60-69 years) and 24.6% (>70 years). Daily or weekly alcohol
      consumption was also related to a higher incidence, of 63.2% and 47.2%,
      respectively. Only 59.7% were known to be hypertensive. Of the hypertensive
      individuals, 57.3% were undergoing some type of treatment. Of those undergoing
      regular treatment, 60.5% presented hypertension. CONCLUSION: The prevalence of
      hypertension was 41.4%, therefore higher than the average verified in some
      studies. This calls the attention for worsened epidemiologic conditions and
      cardiovascular repercussions, thus showing the need for higher public investment
      on education and orientation of these population groups as regards prevention.

PMID- 17546276
TI  - Combined analysis of genetic and environmental factors on essential hypertension
      in a brazilian rural population in the Amazon region.
AB  - OBJECTIVE: In the present study, we evaluated the contribution of six genetic
      polymorphisms of the Renin-Angiotensis-Aldosterone system (RAAS) and clinical
      risk factors in the development of essential hypertension in a Brazilian rural
      population in the Amazon region. METHODS: Eighty-two hypertensive patients and
      seventy-eight normotensive individuals were evaluated. Genotyping for renin (REN
      G1051A), angiotensinogen (AGT) M235T, insertion/deletion of angiotensin
      converting enzyme (ACE I/D), angiotensin II type 1 receptor (AGTR1) A1166C and
      aldosterone synthase (CYP11B2) C344T polymorphisms were performed using
      polymerase chain reaction, with further restriction analysis when required. The
      influence of genetic polymorphisms and clinical risk factors on blood pressure
      variation was assessed by stepwise linear regression. RESULTS: We report the co
      occurrence of clinical risk factors and angiotensin-converting enzyme (ACE) gene
      polymorphism in a Brazilian rural population in the Amazon region. Our results
      indicate that increase of systolic blood pressure (SBP) is favored by ACE I/D- D
      allele and advanced age, while alcohol consumption and aging are associated with
      high diastolic blood pressure (DBP). CONCLUSION: These findings suggest that in
      the Santa Isabel do Rio Negro population, the residents that carry ACE-D allele
      or have an alcohol consumption habit present higher values of SBP and DBP,
      respectively, with the passing of years.

PMID- 17546277
TI  - High blood pressure and some risk factors in a Brazilian capital.
AB  - OBJECTIVES: Estimate the prevalence of hypertension and some cardiovascular risk
      factors in the adult population of a major city in Brazil. METHODS: Descriptive,
      observational, transversal population-based study substantiated by the home
      survey of a simple random sample (>18 years old). Standardized questionnaires
      were used to obtain sociodemographic information, measurements of blood pressure
      (2 measurements), weight, height, and abdominal circumference (AC). Microsoft
      Access and Epi Info 6 were used for data storage and analysis, respectively. The
      last blood pressure reading was used (hypertension: BP>140 x 90 mm Hg). RESULTS:
      The study evaluated 1,739 individuals (87% of the estimated sample). There was a
      predominance of females (65.4%) and mean age was 39.7 years (+/- 15.6); arterial
      hypertension prevalence was 36.4%, higher for the male population (41.8%) when
      compared to females (31.8%). Correlation between Hypertension and Body Mass Index
      was positive, as well as with AC and age. The female gender and higher income
      were protective factors against hypertension. There was no correlation with
      schooling. Prevalence of overweight and obesity were 30.0% and 13.6%,
      respectively; overweight was higher among females and obesity among males. The
      prevalence of smoking was 20.1%, more frequent among males (27.1%), when compared
      to females (16.4%). A sedentary lifestyle was observed in 62.3% of the
      population, with no difference between the genders. Regular alcohol consumption
      was reported by 44.4% of the individuals, being more frequent in males.
      CONCLUSION: Hypertension and other cardiovascular risk factors (particularly
      overweight/obesity) indicators are high, reinforcing the need for objective
      nationwide measures to fight this disease, in order to reduce CVD morbidity and
      mortality.

PMID- 17546278
TI  - Impact analysis of drug-eluting stent in the unified health system budget.
AB  - BACKGROUND: Drug-eluting stents represent an additional option to treat coronary
      artery disease. This technology represents a major breakthrough that may require
      additional funding in the short-term to enable its inclusion in procedures of the
      Unified Health System. OBJECTIVE: To estimate the impact on the Unified Health
      System budget in the first year of use of drug-eluting stents. METHODS: A Budget
      Impact Model was designed to predict the economic impact of the inclusion of drug
      eluting stents in the Unified Health System budget. Data about costs and local
      procedures were collected in multiple sources, specifically procedure volume
      data, hospital costs, cost of stents, drug costs and number of stents used in
      single and multi-vessel procedures. RESULTS: The results in the first year
      indicate that the impact on the Unified Health System is of 12.8% in the best
      scenario and 24.4% in the worst scenario, representing an increase by R$ 24 to 44
      million in the total projected budget. CONCLUSION: Drug-eluting stents have an
      additional cost compared with standard stents in the first year of use in the
      Unified Health System.

PMID- 17546279
TI  - Cost-effectiveness of sirolimus-eluting stents in percutaneous coronary
      interventions in Brazil.
AB  - OBJECTIVES: To compare the cost-effectiveness ratios of sirolimus-eluting stents
      (SES) with bare-metal stents (BMS) under two perspectives: the "supplementary
      medical system" (health plans and private patients) and the public health (SUS)
      system. METHODS: A decision-analytic model using three different therapeutic
      strategies for coronary lesions: percutaneous coronary intervention (PCI) with
      BMS; with SES; or with BMS followed by SES to treat symptomatic restenosis. Study
      endpoints were one-year event-free survival and life expectancy. Decision trees
      were constructed using the results of published registries and clinical trials.
      RESULTS: One-year restenosis-free survival was 92.7% with SES and 78.8% with BMS.
      Estimated life expectancy was very similar for all the strategies, ranging from
      18.5 to 19 years. Under a nonpublic perspective, the cost difference in the first
      year between BMS and SES was R$3,816, with an incremental cost-effectiveness
      ratio of R$27,403 per event avoided in one year. Under the SUS perspective, the
      cost per event avoided in one year was R$47,529. In the sensitivity analysis,
      probability of restenosis, risk reduction expected with SES, the price of the
      stent and cost of treating restenosis were all important predictors. In the Monte
      Carlo simulation, data per years of life saved showed very high cost
      effectiveness ratios. CONCLUSION: In the Brazilian model, the cost-effectiveness
      ratios for SES were elevated. The use of SES was more favorable for patients with
      high risk of restenosis, as it is associated with elevated costs in restenosis
      management of and under a nonpublic perspective.

PMID- 17546280
TI  - Heart failure treatment profile at the beta blockers era.
AB  - OBJECTIVES: The inhibition of the rennin-angiotensin-aldosterone system (RAAS)
      and sympathetic autonomous nervous system has increased the perspective of
      survival in these patients, as well as allowing the improvement of the quality of
      life. The aim of this study was to evaluate the reality of the treatment employed
      and its impact on the disease in patients followed at a specialized heart failure
      (HF) outpatient clinic. METHODS: A sample of 96 patients followed at the HF and
      Transplant Outpatient Clinic of Heart Institute of the University of Sao Paulo
      School of Medicine (InCor -HCFMUSP) were evaluated. The data were collected
      during the ambulatory consultation from the medical files and through physical
      examination. Patients were randomly selected for the study. RESULTS: Most of the
      patients were Functional Class II (42.3%) and evolution stage C (94.9%). The
      medical prescription given to the patients was quite similar to the one
      recommended by the directives. Approximately 95% of them received RAAS inhibitors
      (ACE inhibitor--enalapril and captopril--or angiotensin receptor antagonist-
      losartan), whereas 85% of the patients additionally received beta blockers
      (carvedilol). The mean dose prescribed was also similar to the one used in large
      studies and reached more than 60% of the maximum dose for each medication. The
      hemodynamic data show that patients were stable, despite the intensity of the
      dysfunction and ventricular remodeling observed in these patients. CONCLUSION:
      Patients with HF followed by a specialized medical team receive a medical
      prescription that is closer to the recommended one. These patients, despite the
      marked characteristics of disease severity, achieve hemodynamic and clinical
      stability with an adequate therapeutic optimization.

PMID- 17546281
TI  - Influence of pregnancy on clinical course and fetal outcome of women with
      hypertrophic cardiomyopathy.
AB  - OBJECTIVES: To study clinical evolution of women with HCM during pregnancy; the
      influencing factors of gestation on natural course of HCM and the frequency of
      HCM in their children in early childhood. METHODS: A prospective study was
      conducted in 35 women with HCM; there were 23 pregnant women (PG group) and 12
      nonpregnant control patients (NP group), matched for age and functional class
      (FC). Clinical monthly evaluations were carried out and electrocardiogram and
      transthoracic echocardiography tests were performed. The offspring endpoints
      included stillbirth and prematurity rates and investigation of HCM during
      childhood. RESULTS: No deaths occurred in either group. Cardiac arrhythmias were
      significantly (p< 0.05) more frequent in the NP group (33.3% vs. 13.4%), and no
      differences were observed between the groups (p>0.05) in heart failure (30.3% vs.
      16.6%) or ischemic stroke (4.3% vs. 8.3%) rates. In the PG group, required
      hospitalization for treatment of cardiac complication was more frequent (p=0.05)
      in patients with family history of HCM (71.4% vs. 25.0%). Cesarean section was
      performed in 12 (52%) patients, for obstetrical reasons; there were 7 (30.4%)
      premature babies and 1 (4.3%) neonatal death. One child was clinically diagnosed
      as having HCM, and his genetic study identified a mutation in the beta myosin
      heavy chain gene, located on chromosome 14. CONCLUSION: Heart failure is a
      frequent cardiac complication in women with HCM during pregnancy, particularly in
      patients with family history of the disease, but this did not influence the
      natural course of HCM. In one child, clinical examination allowed HCM
      identification during early childhood.

PMID- 17546282
TI  - Macroscopic aspects of chronic Chagas heart disease in aging.
AB  - OBJECTIVE: To describe the macroscopic characteristics of chronic Chagas heart
      disease in autopsied elderly. METHODS: The elderly studied were 60 or older.
      Twenty of them had chronic Chagas heart disease (CHD) and positive serology for
      the disease, and 14 had no heart disease (WHD) nor morphological changes
      suggestive of it and were serologically negative for Chagas disease. RESULTS: The
      CHD elderly had cardiac weight greater than the WHD (385 +/- 141.1 vs 306.8 +/-
      62.1g, respectively; p > 0.05), in addition to significantly higher heart weight
      to-body weight ratio (0.71% [0.5-1.42%] vs 0.59% [0.47-0.91%] p < 0.05). When
      compared, the CHD elderly presented lower fibrous thickening and/or
      atherosclerosis in the ascending aorta, mitral and tricuspid valves, and left and
      right coronaries than the WHD elderly. In the aortic and mitral valves, the
      lesions were significantly less severe (p < 0.05). Left ventricular apical lesion
      was observed in 45% of the CHD elderly, and intracardiac thrombosis in the left
      ventricle was found in 10% of them. CONCLUSION: Fibrous thickening and/or
      atherosclerosis were found to be less severe in the valves and arteries of the
      CHD elderly. Moreover, heart weight and intracardiac thrombosis frequency were
      lower than those detailed in the literature for non-elderly individuals.

PMID- 17546283
TI  - Blood pressure measurement in children and adolescents: guidelines of high blood
      pressure recommendations and current clinical practice.
AB  - OBJECTIVE: To determine, in a school-based sample of children and adolescents,
      aged from 7 to 17 years, of both gender, in public and private schools, the
      frequency of students already submitted to blood pressure measure. METHODS: A
      cross-sectional study was carried out, sampling from a population pool of
      elementary and middle schools, randomly selected. The sample was calculated based
      on the expected prevalence of hypertension for the age group. Data were collected
      through a questionnaire. Blood pressure was measured twice and hypertension was
      defined as mean systolic and/or diastolic blood pressure over the 95th
      percentile. Independent variables studied: sex; age groups; economic status;
      public/private school. RESULTS: The final sample included 1253 students. The
      response rate was 97%: 1215 students; 531 males; mean age 12,4 +/- 3 years (236
      from 7 to 9 years; 638 from 10 to 14 years; 341 from 15 to 17 years). Prevalence
      of hypertension was 7.7%; 348 students (29%) were already submitted to blood
      pressure measures (54% once; 35% 2 to 4 times; 11% 5 or more times). High
      economic status, private school and adolescent group were significantly
      associated to previous blood pressure measure. CONCLUSION: Despite of pediatric
      consensus statements and guidelines recommendations about importance of blood
      pressure measure at every examination after age 3 years, there is a very low
      frequency of this practice (29%) in children and adolescents.

PMID- 17546284
TI  - Epicardial lesions in Chagas' heart disease reflect an inflammatory process.
AB  - OBJECTIVE: Furnish a more detailed anatomicopathological description of the
      epicardial lesions in chronic chagasic cardiopathy, evaluate their incidence and
      discuss their probable pathogenesis METHODS: We examined the hearts of 39 chronic
      chagasic cardiopathy patients who underwent autopsies and submitted to
      histological analysis the epicardial lesions. RESULTS: Milk spots, characterized
      by well defined white areas in the epicardium were found in 80% of the cases,
      mainly on the anterior face of the right ventricle. Histological analysis
      revealed abrupt fibrous thickening of the epicardium, with no elastic fibers,
      inflammation or blood vessels. Chagasic rosary, characterized by small round
      whitish granules deposited sequentially along the coronary vessels were present
      in 23% of the hearts. They presented the same histological structure as the milk
      spots, but interestingly were only found immediately above the coronary artery
      branches. Villous plaque was found on the apex or anterior face of 21% of the
      hearts. It is characterized by an exophytic aspect, probably due to previous
      localized pericardial adhesion. Microscopic analysis revealed foci of
      inflammatory infiltrate and vascular proliferation, typical of epicarditis still
      under organization. In addition to the lesions described above, the vast majority
      of cases presented sparse mononuclear inflammatory cells with occasional foci.
      CONCLUSION: We concluded that epicardial lesions related to chronic chagasic
      heart disease are probably a result of epicardial reactions to chronic
      inflammatory process.

PMID- 17546286
TI  - [What are we good at?].

PMID- 17546287
TI  - Proposal of a new technique for bile duct reconstruction after iatrogenic injury:
      study in dogs and review of the literature.
AB  - PURPOSE: Interposition of a jejunal tube between the common bile duct and
      duodenum. METHODS: Five adult mongrel dogs of both sexes, weighing on average
      22.3 kg (18 to 26.5 kg), were used. Obstructive jaundice was induced by ligation
      of the distal common bile duct. After one week, a 2.5-cm long jejunal tube was
      fabricated from a segment of the loop removed 15 cm from the Treitz angle and
      interposed between the common bile duct and duodenum. RESULTS: The animals
      presented good clinical evolution and no complications were observed. After 6
      weeks, complete integration was noted between the bile duct mucosa, tube and
      duodenum and a significant reduction in total bilirubin and alkaline phosphatase
      was observed when compared to the values obtained one week after ligation of the
      common bile duct. CONCLUSION: The jejunal tube interposed between the dilated
      bile duct and duodenum showed good anatomic integration and reduced total
      bilirubin and alkaline phosphatase levels in the animals studied.

PMID- 17546288
TI  - Validation of the ovine fetus as an experimental model for the human
      myelomeningocele defect.
AB  - PURPOSE: To produce a myelomeningocele-like human defect in the ovine fetus and
      validate this experimental model in our population. METHODS: A prospective study
      on 12 pregnant sheep of a crossed Hampshire/Down breed where a spinal defect was
      surgically created between Day 75 and Day 77 after conception. The technique
      consisted of a hysterotomy with exposure of fetal hind limbs and tail up to the
      mid spine. Fetal skin, paravertebral muscles, and 4 posterior spinal arches were
      excised, exposing the spinal cord. Duramater was opened and the medulla was
      incised until the medullar canal. Animals were euthanized at 139 days of
      gestation for fetal evaluation. The central nervous system was submitted to post
      mortem magnetic resonance imaging (MRI) and the spine was submitted to
      pathological examination. RESULTS: The defect was created in 13 fetuses and 5
      survived. Mean gestational age at necropsy was 121.6 days (varying from 93 to 145
      days). Macroscopically, the defect was present in 4 cases. Microscopy revealed a
      flattened medulla with disappearance of the medullar canal and disruption of
      normal medullar architecture with neuronal apoptosis and/or fusion of the
      piamater and duramater. The MRI showed herniation of the cerebellum into the
      cervical canal and syringomyelia. CONCLUSIONS: The surgically produced defect
      mimics the defect found in the human fetus, including the Arnold-Chiari
      malformation. Post-mortem MRI was used for the first time in our study and proved
      an excellent alternative for demonstrating the cerebellar herniation. We
      standardized the technique for creating the defect in our population.

PMID- 17546289
TI  - Biosynthetic cellulose induces the formation of a neoduramater following pre
      natal correction of meningomyelocele in fetal sheep.
AB  - PURPOSE: The aim of this study was to compare the effectiveness of two dura-mater
      substitutes, namely human acellular dermal matrix (HADM) and biosynthetic
      cellulose (BC), in repairing, in utero, surgically-induced meningomyelocele (MMC)
      in fetal sheep. METHODS: A neural tube defect was created at 74-77 days gestation
      in 36 fetal sheep. They were divided into 3 groups, the control group that did
      not receive pre-natal corrective surgery, and the other two groups that received
      corrective surgery using HADM (Group A) or BC (Group B). Both materials were used
      as a dura-mater substitutes between the neural tissue and the sutured skin.
      Correction was performed at gestation day 100 and the fetuses were maintained in
      utero until term. Sheep were sacrificed on gestation day 140. The fetal spine was
      submitted to macro and microscopic analysis. At microscopy, adherence of the
      material to the skin and neural tissue was analyzed. RESULTS: In the initial
      phase (pilot), experimentally-induced MMC was performed on 11 fetuses and 4
      survived (37%). In the second phase (study), 25 fetuses received surgery and 17
      survived (68%). In the study group, 6 fetuses did not undergo repair (control
      group), 11 cases were submitted to corrective surgery (experimental group) and
      one fetal loss occurred. Of the surviving cases in the experimental group, 4
      constituted Group A and 6 in Group B. Macroscopically, skin and underlying
      tissues where easily displaced from the BC in all cases it was used; in contrast,
      HADM adhered to these tissues. To compare the adherence, 4 cases from Group A and
      4 in Group B were studied. We observed adherence, host cell migration and vessel
      proliferation into the HADM all sections from Group A and this aspect was not
      present in any cases in Group B (p < 0.05). In Group B, we also observed that a
      new fibroblast layer formed around the BC thus protecting the medulla and
      constituting a "neoduramater". CONCLUSION: The use of BC seems to be more
      adequate as a dura-mater substitute to cover the damaged neural tissue than HADM.
      It seems promising for use in the in utero correction of MMC because to does not
      adhere to neural tissue of superficial and deep layers ("tethered spinal cord").
      Thus, BC minimizes the mechanical and chemical intrauterine damage to the spinal
      medulla.

PMID- 17546290
TI  - Ultrasonography for measuring rectus abdominis muscles diastasis.
AB  - PURPOSE: Preoperative imaging evaluation may be useful for determining the
      position of recti abdominis muscles before their correction. The purpose of this
      study is to evaluate the accuracy of ultrasonography to measure the width of
      rectus abdominis muscle diastasis. METHODS: Rectus diastasis was measured by
      ultrasonography preoperatively in 20 females. Rectus diastasis was measured in
      seven levels along the anterior rectus sheath by ultrasound after sustained deep
      inspiration and after expiration. Rectus diastasis, at the same levels, was also
      measured after its exposition during abdominoplasty by two independent observers,
      using a surgical compass. These values were compared using Wilcoxon's statistical
      text, for non independent values. RESULTS: There was no significant difference
      between the values obtained by ultrasound and those measured during surgery in
      the supra-umbilical levels and at the level of the umbilicus. However, below the
      umbilicus these values differed significantly, showing smaller values in the
      imaging evaluation. CONCLUSION: Ultrasonography is an accurate method to measure
      rectus diastasis above the umbilicus and at the umbilical level.

PMID- 17546291
TI  - Comparison between textured silicone implants and those bonded with expanded
      polytetrafluoroethylene in rats.
AB  - PURPOSE: Comparison of the inflammatory reaction promoted by textured silicone
      implants and that caused by the implant bonded with e-ptfe. METHODS: One-hundred
      and fifty rats were divided into three equal groups (control, silicone, and
      bonded e-ptfe). These groups were subdivided into five groups, according to the
      second operation, i.e., 7,30,60,90 and 180 days. Histology of the peri-implant
      tissue was analyzed by morphometry with blood count (neutrophils, lymphocytes,
      macrophages, fibroblasts and capillaries). RESULTS: Comparison of subgroups
      7,30,60,90, 180 days: - neutrophils: silicone: > in subgroup 7 days; bonded e
      ptfe: > in subgroups 7 and 30 days; - lymphocytes: silicone: > in subgroup 7 and
      180 days; bonded e-ptfe: > in subgroup 180 days; - macrophages: silicone: > in
      subgroup 7 and 60 days; bonded e-ptfe: > in subgroup 7,30 and 60 days; -
      fibroblasts: silicone: > in subgroup 30 and 60 days;- vascular volume: silicone:
      in subgroup 7, 60 and 90 days; bonded e-ptfe: > in subgroup 7 days. Comparison of
      groups: neutrophils : 7 days: > in silicone and bonded e-ptfe; 30 days: > in
      bonded e-ptfe; - lymphocytes: - 7,30,90 and 180 days: in the control;
      macrophages: - 7,30 and 60 days: > in silicone & bonded e-ptfe; 180 days > in
      silicone; fibroblasts: - 7,30 and 90 days: > in silicone and bonded e-ptfe; 180
      days: > in bonded e-ptfe; vascular volume 7,60,90 and 180 days: > in silicone and
      bonded e-ptfe; 30 days: > in bonded e-ptfe. CONCLUSIONS: The acute stage of the
      inflammatory response was more severe and irregular in the silicone implant; both
      the silicone implant and the silicone bonded with e-ptfe promoted chronic
      inflammatory reaction and weak foreign body inflammatory response. These
      reactions were greater in the silicone implant group.

PMID- 17546292
TI  - Bacterial translocation in rats nonfunctioning diverted distal colon.
AB  - PURPOSE: To investigate whether the alterations of the diverted colon segment
      mucosa, evidenced in fecal colitis, would be able to alter Bacterial
      Translocation (BT). METHODS: Sixty-two Wistar male rats ranging from 220 to 320
      grams of weight, were divided in two groups: A (Colostomy) and B (Control), with
      31 animals each one. In group A, all animals underwent end colostomy, one stoma,
      in ascending colon; and in the 70th POD was injected in five rats, by rectal
      route diverted segment - 2 ml of a 0.9% saline solution in animals (A1 subgroup);
      in eight it was inoculated, by rectal route, 2 ml of a solution containing
      Escherichia coli ATCC 25922 (American Type Culture Collection), in a
      concentration of 10(8) Colony Forming Unit for milliliters (CFU/ml) - A2
      Subgroup; in ten animals the same solution of E. coli was inoculated, in a
      concentration of 10(11) CFU/ml (A3 Subgroup); and in eight it was collected part
      of the mucus found in the diverted distal colonic segment for neutral sugars and
      total proteins dosage (A4 subgroup). The animals from the group B underwent the
      same procedures of group A, but with differences in the colostomy confection. In
      rats from subgroups A1, A2, A3, B1, B2, and B3 2 ml of blood were aspirated from
      the heart, and fragments from mesenteric lymphatic nodule, liver, spleen, lung
      and kidney taken for microbiological analysis, after their death. This analysis
      consisted of evidencing the presence of E. coli ATCC 25922 CFU. Mann-Whitney and
      ANOVA Tests were applied as analytic techniques for association of variables.
      RESULTS: The occurrence of BT was evidenced only in those animals in which
      inoculated concentration of E. coli ATCC 25922, reached levels of 10(11)CFU/ml,
      i.e. in Subgroups A3 and B3, although, being significantly greater (80%) in those
      animals without colostomy (subgroup B3) when compared to the ones with colostomy
      (20%) from the subgroup A3 (P <0.05). Lung, liver and mesenteric lymphatic
      nodules were the tissues with larger percentile of bacterial recovery, so much in
      subgroup A3, as in B3. Blood culture was considered positive in 60% of the
      animals from subgroup B3 and in 10% of those from subgroup A3 (p <0.05). There
      was greater concentration of neutral sugars, in subgroup A4 - mean 27.3mg/ml -,
      than in subgroup B4 - mean 8.4 mg/ml - (P <0.05). CONCLUSION: The modifications
      in the architecture of intestinal mucosa in colitis following fecal diversion can
      cause alterations in the intestinal barrier, but it does not necessarily lead to
      an increased frequency of BT.

PMID- 17546293
TI  - Pancreatic intraepithelial neoplasia and ductal adenocarcinoma induced by DMBA in
      mice: effects of alcohol and caffeine.
AB  - PURPOSE: To evaluate the effects of alcohol and caffeine in a pancreatic
      carcinogenesis mouse model induced by 7,12-dimethylbenzantracene (DMBA),
      according to the PanIN classification system. METHODS: 120 male, Mus musculus, CF
      1 mice were divided into four groups. Animals received either water or caffeine
      or alcohol or alcohol + caffeine in their drinking water. In all animals, 1 mg of
      DMBA was implanted into the head of the pancreas. After 30 days, euthanasia was
      performed; excised pancreata were then fixed in formalin, stained with
      hematoxylin-eosin and categorized as follows: normal ducts, reactive hyperplasia,
      PanIN-1A, PanIN-1B, PanIN-2, PanIN-3 or adenocarcinoma. RESULTS: PanIN lesions
      were verified in all groups. Adenocarcinoma was detected in 15% of animals in the
      caffeine group, 16.6% in the water group, 23.8% in the alcohol + caffeine group
      and 52.9% in the alcohol group (P<0.05). CONCLUSIONS: The experimental pancreatic
      carcinogenesis mouse model using DMBA effectively induces PanIN lesions and
      pancreatic adenocarcinoma. This study verified the association between alcohol
      use and pancreatic adenocarcinoma; caffeine did not present the same effect.

PMID- 17546294
TI  - Does troncular vagotomy modify the proliferative gastric lesions induced in rats
      by duodenogastric reflux?
AB  - PURPOSE: to investigate if combining VT to DGR through the pylorus can modulate
      the biological behavior of PL induced by DGR and to verify if TV alone can induce
      morphologic lesions in the gastric mucosa. METHODS: 62 male Wistar rats were
      assigned to four groups: 1 - Control (CT) gastrotomy; 2 - Troncular Vagotomy (TV)
      plus gastrotomy; 3 - Duodenogastric reflux through the pylorus (R) and 4 -
      Troncular vagotomy plus DGR (RTV). The animals were killed at the 54 week of the
      experiment. DGR was obtained by anastomosing a proximal jejunal loop to the
      anterior gastric wall. TV was performed through isolation and division of the
      vagal trunks. Gastrotomy consisted of 1 cm incision at the anterior gastric wall.
      PL were analyzed gross and histologically in the antral mucosa, at the
      gastrojejunal stoma and at the squamous portion of the gastric mucosa. RESULTS:
      Groups R and RTV developed exophytic lesions in the antral mucosa (R=90.9%;
      RTV=100%) and at the gastrojejunal stoma (R=54.54%; RTV=63.63%). Histologically
      they consisted of proliferative benign lesions, without cellular atypias,
      diagnosed as adenomatous hyperplasia. Both groups exposed to DGR presented
      squamous hyperplasia at the squamous portion of the gastric mucosa (R= 54.5%;
      RTV= 45.4%). TV, alone, did not induce gross or histological alterations in the
      gastric mucosa. TV did note change the morphologic pattern of the proliferative
      lesions induced by DGR. CONCLUSIONS: DGR induces the development of PL in the
      pyloric mucosa and at the gastrojejunal stoma. TV does not change the morphologic
      pattern of the proliferative lesions induced by DGR. TV alone is not able to
      induce morphologic lesions in the gastric mucosa.

PMID- 17546295
TI  - Glutamine or whey-protein supplementation on alloxan-induced diabetic rats.
      Effects on CD4+ and CD8+ lymphocytes.
AB  - PURPOSE: To evaluate the effects of glutamine (L-Gln) or whey-protein
      supplementation on CD4+ and CD8+ lymphocytes in alloxan-induced diabetic rats.
      METHODS: Thirty-two healthy male Wistar rats were used in the experiment. Eight
      rats served as baseline controls (G-1). The remaining 24 animals received alloxan
      150 mg/Kg intraperitonially dissolved in buffer solution and were equally
      distributed in 3 subgroups, upon induction of diabetes mellitus, and treated as
      follows: (G2): saline, 2.0 ml; (G3): glutamine solution (0.7 g/kg), 2.0 ml; and
      (G4): whey-protein (WPS) solution (0.7 g/kg), 2.0 ml. All solutions were
      administered by daily 7:00 AM gavages during 30 days. Next, arterial blood
      samples (3.0 ml) were collected from anesthetized rats for CD4+ and CD8+
      lymphocyte count through flow cytometry technology. RESULTS: CD4+ and CD8+ counts
      decreased significantly in all groups compared with baseline values (G1). G2 rats
      CD4+/CD8+ ratio decreased significantly compared with G1. CD4+/CD8+ ratio
      increased significantly (>260%) in L-Gln treated group (G3) compared with saline
      treated rats (G2). There were no statistical differences in lymphocyte counts
      (CD4+ and CD8+) between L-Gln (G3) and saline-treated (G2) groups. There was a
      significant reduction in CD8+ cell count compared with CD4+ cell count in L-Gln
      treated rats (G3). CONCLUSION: The offer of L-Gln to experimental diabetic rats
      enhances the immunologic response to infection.

PMID- 17546296
TI  - Superior laryngeal nerve anatomy in corpses not preserved in formaldehyde:
      contribution to the operative technique.
AB  - PURPOSE: To carry out an anatomic study of superior laryngeal nerve in not
      preserved in formaldehyde and not frozen corpses. METHODS: Thirty-eight male
      corpses from the Minas Gerais Medico-legal Institute (IML) were studied. In 18
      corpses dissection was performed bilaterally and in 20 only on the left side,
      total number 56 nerves dissected. Their descriptive segments measurements and the
      anatomic relations with the cervical structures of the region were described.
      This nerve was statistically analyzed; the variables were corpse side (Friedman's
      test (p<0.05), height (Pearson), racial group (Kruskal-Wallis). RESULTS: The
      superior laryngeal nerve presented a definite anatomical disposition in all the
      56 nerves studied, emerging from the nervus vagus inferior ganglion. The superior
      laryngeal nerve trunk was in average longer in corpses over 25 years old
      (p<0.05). Significant differences (p<0.05) between the internal and external
      branches were observed in all racial groups, and the internal branch average was
      inferior to the external branch average. There were not significant differences
      between the 18 studied corpses' left and right sides paired measurements.
      CONCLUSIONS: Concerning emergence, trunk, bifurcation and major branches, the 56
      studied nerves disposition had a definite anatomic pattern. The superior
      laryngeal nerve trunk was in average longer in corpses over 25 years old. In this
      study, the external branch of the laryngeal nerve was in average longer than the
      internal branch.

PMID- 17546297
TI  - Anesthetic experimental device for small animal.
AB  - PURPOSE: The difficulty to anesthetize small laboratory animals with vaporizer
      prompted us to go in search of new materials, and create new techniques. The
      improved equipment of anesthesia we looked for should be low cost, practical,
      versatile, and its management serve ethical, teaching, and research purposes.
      METHODS: The new components of the equipment were: the vaporizer, the
      unidirectional valve, the glass cylinder filled with water, the flow guidance y
      shape tube, the flow regulators, the mask modifications, and another free airway
      for emergency occurrence. A test was done with 30 Wistar rats, Rattus norvegicus
      albinus, divided into three groups with 10 rats for each one. Groups 1, 2 and 3
      were anesthetized with Ether, Halothane and Sevoflurane respectively, using the
      new gadget. The anesthetic induction time, the breathing rhythm alteration during
      an anesthesia pre-established time (10 minutes), and the recovery time were
      observed. RESULTS: The equipment enabled an easy handling, and fulfilled a larger
      safeness and stability during the induction and anesthetic management. The test
      showed it was possible to make use of several anesthetic agents. CONCLUSION: The
      device is effective, and turns the anesthesia procedure into a very easy practice
      with low-cost. It should be recommended for experimental surgery, teaching and
      research.

PMID- 17546298
TI  - What will it cost to attain the health MDGs?

PMID- 17546299
TI  - Evidence to action in the developing world: what evidence is needed?

PMID- 17546300
TI  - Appropriate information-communications technologies for developing countries.

PMID- 17546301
TI  - WHO to launch first essential medicines list for children.

PMID- 17546302
TI  - Making malaria deaths easier to count.

PMID- 17546303
TI  - WHOs longest serving leader.

PMID- 17546306
TI  - Estimated global resources needed to attain universal coverage of maternal and
      newborn health services.
AB  - OBJECTIVE: To estimate the amount of additional resources needed to scale up
      maternal and newborn health services within the context of the Millennium
      Development Goals, and to inform countries, donors and multilateral agencies
      about the resources needed to achieve these goals. METHODS: A costing model based
      on WHOs clinical guidelines was used to estimate the incremental resource needs
      for maternal and newborn health care in 75 countries. The model estimated the
      costs for care during pregnancy, childbirth, the neonatal period and the
      postpartum period, as well as the costs for postpartum family planning and
      counselling, abortion and post-abortion care; programme-level costs were also
      estimated. An ingredients-based approach, with financial costs for the years 2006
      to 2015 as the output, allowed estimates to be made of country-specific and year
      specific populations, unit costs and scale-up rates. Two scenarios using
      different scale-up rates were used (moderate and rapid). FINDINGS: The results
      show that a minimum yearly average increase in resources of US$ 3.9 billion is
      needed, although annual costs increase over the time period of the model. When
      more rapid rates of scale-up are assumed, this minimum figure may be as high as
      US$ 5.6 billion per year. The 10-year estimated incremental costs range from US$
      39.3 billion for a moderate scale-up scenario to US$ 55.7 billion for the rapid
      scale-up scenario. CONCLUSION: These projections of future financial costs may be
      used as a starting point for mobilizing global resources. Countries will have to
      further refine these estimates, but these figures may serve as goals towards
      which donors can direct their plans. Further research is needed to measure the
      costs of health system reforms, such as recruiting, training and retaining a
      sufficient number of personnel.

PMID- 17546307
TI  - Determinants of womens participation in cervical cancer screening trial,
      Maharashtra, India.
AB  - OBJECTIVE: To determine the factors associated with participation in cervical
      cancer screening and follow-up treatment in the context of a randomized
      controlled trial. The trial was initiated to evaluate the efficacy and cost
      effectiveness of visual inspection with acetic acid, cytological screening and
      testing for human papillomavirus in reducing the incidence of and mortality from
      cervical cancer in Maharashtra, India. METHODS: Between October 1999 and November
      2003 women aged 30-59 years were randomized to receive one of the three tests or
      to a control group. Participation was analysed for all three intervention arms.
      The differences between those who were screened versus those who were not was
      analysed according to the sociodemographic characteristics of the 100,800
      eligible women invited for screening. Those who were treated versus those who
      were not were analysed according to the sociodemographic characteristics of the
      932 women diagnosed with high-grade lesions. Participation in screening and
      compliance with treatment were also analysed according to the type of test used.
      FINDINGS: Compared with women who were not tested, screened women were younger
      (aged 30-39), better educated and had ever used contraception. A higher
      proportion of screened women were married and a lower proportion had never been
      pregnant. Of the 932 women diagnosed with high-grade lesions or invasive cancer,
      85.3% (795) received treatment. Women with higher levels of education, who had
      had fewer pregnancies and those who were married were more likely to comply with
      treatment. There were no differences in rates of screening or compliance with
      treatment when results were analysed by the test received. CONCLUSIONS:
      Irrespective of the test being used, good participation levels for cervical
      cancer screening can be achieved in rural areas of developing countries by using
      appropriate strategies to deliver services. Communication methods and delivery
      strategies aimed at encouraging older, less-educated women, who have less contact
      with reproductive services, are needed to further increase screening uptake.

PMID- 17546308
TI  - Tsunami mortality in Aceh Province, Indonesia.
AB  - OBJECTIVE: Nine tsunami-affected districts in Aceh, Indonesia, were surveyed
      between February and August 2005 to characterize tsunami mortality. METHODS: The
      surveys employed a two-stage cluster methodology with probability proportional to
      size sampling, and encompassed 1653 tsunami-displaced households with a pre
      tsunami population of 10 063 individuals. FINDINGS: Of the original pre-tsunami
      population, a total of 1642 people, or 17%, were reported as dead or missing in
      the tsunami. Crude mortality rates in the four survey areas ranged from a high of
      23.6% in Aceh Jaya district on the west coast to 5.3% on the east coast. Age
      specific mortality rates followed a similar pattern across the four survey areas,
      with the highest mortality concentrating in the youngest children (aged 0-9
      years) and oldest adults (70+). The risk of mortality was significantly greater
      among females than males; this difference was most pronounced among individuals
      between ages 10 and 69 years, and diminished among younger and older age groups.
      CONCLUSION: Mortality risk in the 2004 Asian tsunami varied by geographic
      location, age and sex. The districts of Aceh Jaya, Banda Aceh and Aceh Besar
      experienced the greatest mortality. Risk of death was highest among females, and
      among the oldest and youngest population subgroups. While the full human impact
      of the Asian tsunami in Aceh Province, in terms of lives lost or damaged, may
      never be fully measured, the resulting female deficit will likely be the tsunamis
      most deeply felt and prolonged impact.

PMID- 17546309
TI  - The availability and affordability of selected essential medicines for chronic
      diseases in six low- and middle-income countries.
AB  - OBJECTIVE: To assess the availability and affordability of medicines used to
      treat cardiovascular disease, diabetes, chronic respiratory disease and glaucoma
      and to provide palliative cancer care in six low- and middle-income countries.
      METHODS: A survey of the availability and price of 32 medicines was conducted in
      a representative sample of public and private medicine outlets in four
      geographically defined areas in Bangladesh, Brazil, Malawi, Nepal, Pakistan and
      Sri Lanka. We analysed the percentage of these medicines available, the median
      price versus the international reference price (expressed as the median price
      ratio) and affordability in terms of the number of days wages it would cost the
      lowest-paid government worker to purchase one month of treatment. FINDINGS: In
      all countries<or=7.5% of these 32 medicines were available in the public sector,
      except in Brazil, where 30% were available, and Sri Lanka, where 28% were
      available. Median price ratios varied substantially, from 0.09 for losartan in
      Sri Lanka to 30.44 for aspirin in Brazil. In the private sector in Malawi and Sri
      Lanka, the cost of innovator products (the pharmaceutical product first given
      marketing authorization) was three times more than generic medicines. One month
      of combination treatment for coronary heart disease cost 18.4 days wages in
      Malawi, 6.1 days wages in Nepal, 5.4 in Pakistan and 5.1 in Brazil; in Bangladesh
      the cost was 1.6 days wages and in Sri Lanka it was 1.5. The cost of one month of
      combination treatment for asthma ranged from 1.3 days wages in Bangladesh to 9.2
      days wages in Malawi. The cost of a one-month course of intermediate-acting
      insulin ranged from 2.8 days wages in Brazil to 19.6 in Malawi. CONCLUSION:
      Context-specific policies are required to improve access to essential medicines.
      Generic products should be promoted by educating professionals and consumers, by
      implementing appropriate policies and incentives, and by introducing market
      competition and/or price regulation. Improving governance and management
      efficiency, and assessing local supply options, may improve availability. Prices
      could be reduced by improving purchasing efficiency, eliminating taxes and
      regulating mark-ups.

PMID- 17546310
TI  - Infant feeding counselling for HIV-infected and uninfected women: appropriateness
      of choice and practice.
AB  - OBJECTIVE: To examine infant feeding intentions of HIV-infected and uninfected
      women and the appropriateness of their choices according to their home resources;
      and to determine their adherence to their intentions in the first postnatal week.
      METHODS: Feeding intentions of pregnant women were compared against four
      resources that facilitate replacement feeding: clean water, adequate fuel, access
      to a refrigerator and regular maternal income. First-week feeding practices were
      documented. FINDINGS: The antenatal feeding intentions of 1253 HIV-infected women
      were: exclusive breastfeeding 73%; replacement feeding 9%; undecided 18%. Three
      percent had access to all four resources, of whom 23% chose replacement feeding.
      Of those choosing replacement feeding, 8% had access to all four resources. A
      clean water supply and regular maternal income were independently associated with
      intention to replacement feed (adjusted odds ratio (AOR) 1.94, 95% confidence
      interval (CI) 1.2-3.2; AOR 2.1, 95% CI: 1.2-3.5, respectively). Significantly
      more HIV-infected women intending to exclusively breastfeed, rather than
      replacement feed, adhered to their intention in week one (exclusive breastfeeding
      78%; replacement feeding 42%; P<0.001). Of 1238 HIV-uninfected women, 82%
      intended to exclusively breastfeed; 2% to replacement feed; and 16% were
      undecided. Seventy-five percent who intended to exclusively breastfeed adhered to
      this intention postnatally, and only 11 infants (<1%) received no breast milk.
      The number of antenatal home visits significantly influenced adherence to feeding
      intention. CONCLUSION: Most HIV-infected women did not have the resources for
      safe replacement feeding, instead choosing appropriately to exclusively
      breastfeed. Adherence to feeding intention among HIV-infected women was higher in
      those who chose to exclusively breastfeed than to replacement feed. With
      appropriate counselling and support, spillover of suboptimal feeding practices to
      HIV-negative women is minimal.

PMID- 17546311
TI  - Trichomoniasis and bacterial vaginosis in pregnancy: inadequately managed with
      the syndromic approach.
AB  - OBJECTIVE: To measure the prevalence of Trichomonas vaginalis (TV) infection and
      bacterial vaginosis (BV) among pregnant women in Botswana, and to evaluate the
      syndromic approach and alternative management strategies for these conditions in
      pregnancy. METHODS: In a cross-sectional study, 703 antenatal care attendees were
      interviewed and examined, and specimens were collected to identify TV, BV,
      Candida species, Chlamydia trachomatis and Neisseria gonorrhoeae. Information on
      reproductive tract infections earlier in pregnancy was obtained from a structured
      interview and the antenatal record. FINDINGS: TV was found in 19% and BV in 38%
      of the attendees. Three-fourths of women with TV or BV were asymptomatic.
      Syndromic management according to the vaginal discharge algorithm would lead to
      substantial under-diagnosis and over-treatment of TV and BV. Signs of vaginal
      discharge were more predictive of the presence of these conditions than were
      symptoms. Among the 546 attendees on a repeat antenatal visit, 142 (26%) had been
      diagnosed with vaginal discharge earlier in their pregnancy--14 of them twice. In
      143 cases, an attendee was diagnosed with vaginal discharge in the second or
      third trimester; however, metronidazole had been prescribed only 17 times (12%).
      CONCLUSION: Diagnosis and treatment of TV and BV among pregnant women in sub
      Saharan Africa presents major challenges. Half the pregnant women in this study
      were diagnosed with TV or BV, but these conditions were not detected and treated
      during antenatal care with syndromic management. Also, health workers did not
      adhere to treatment guidelines. These results indicate that management guidelines
      for TV and BV in antenatal care should be revised.

PMID- 17546312
TI  - A financial road map to scaling up essential child health interventions in 75
      countries.
AB  - OBJECTIVE: To estimate the additional resources required to scale up
      interventions to reduce child mortality and morbidity within the context of the
      fourth Millennium Development Goals aim to reduce mortality among children aged<5
      years by two-thirds by 2015. METHODS: A costing model was developed to estimate
      the financial resources needed in 75 countries to scale up priority interventions
      that address the major causes of mortality among children aged < 5 years,
      including malnutrition, pneumonia, diarrhoea, malaria and key newborn causes of
      death such as sepsis. Calculations were made using bottom-up and ingredients
      based approaches; this allowed financial costs to be estimated for each
      intervention, country and year. Costs reflect WHO guidelines on inputs and
      delivery strategies and encompass the delivery of interventions at community and
      facility levels. These costs also include programme-specific investments needed
      at national level and district level. FINDINGS: The scale-up scenario predicts
      that an additional US$ 52.4 billion will be required for the period 2006-2015.
      This represents an increase in total per-capita health expenditure in the 75
      countries of US$ 0.47 in 2006; this is projected to increase to US$ 1.46 in 2015.
      Projected costs in 2015 are equivalent to increasing the average total health
      expenditure from all financial sources in the 75 countries by 8% and raising
      general government health expenditure by 26% over 2002 levels. (The latest data
      available at the time of the study were for 2002.) The scale-up scenario
      indicates that countries with weak health systems may experience difficulties
      mobilizing enough domestic public funds. CONCLUSIONS: While the results are
      approximate estimates, they show a substantial investment gap that low- and
      middle-income countries and their development partners need to bridge to reach
      the fourth Millennium Development Goal.

PMID- 17546313
TI  - Improving national data collection systems from voluntary counselling and testing
      centres in Kenya.
AB  - PROBLEM: Voluntary counselling and testing (VCT) data from the registered sites
      in Kenya have been fraught with challenges, leading to insufficient statistics in
      the national office for planning purposes. An exercise was carried out to
      determine the barriers to the flow of data in VCT sites in Kenya. APPROACH: A
      record-based survey was conducted at 332 VCT sites in Kenya. Data from on-site
      records were compared with those in the national office. The exercise was
      conducted in 2004 between 5 September and 15 October. LOCAL SETTING: All
      registered VCT sites in Kenya. RELEVANT CHANGES: After the exercise, various
      measures to enhance VCT data collection and reporting were implemented. They
      include the provision of a uniform data collection and reporting tool to all the
      districts in the country, the strengthening of a feedback mechanism to update
      provinces and districts on their reporting status and increased support to the
      data component of the national quality assurance for VCT. LESSONS LEARNED:
      Periodical field visits by the national officials to offer on-the-job training
      about data management to data collectors and to address data quality issues can
      dramatically improve the quality and completeness of VCT reports. The perceived
      relevance of the data and the data collection process to those working at the
      sites is the critical factor for data quality and timeliness of reporting.

PMID- 17546314
TI  - Setting priorities for health research: lessons from low- and middle-income
      countries.

PMID- 17546315
TI  - Saving womens lives: evidence-based recommendations for the prevention of
      postpartum haemorrhage.

PMID- 17546317
TI  - [Reviews, systematic reviews, and essays in public health].

PMID- 17546318
TI  - [Socioeconomic inequality and mental health: a Latin American literature review].
AB  - This study provides a review of the scientific output in Latin America concerning
      the impact of socioeconomic status (SES) on mental disorders and drug use or
      addiction. International and regional databases were analyzed. According to the
      majority of the studies, adults and adolescents with low SES showed increased
      risk of mental disorders, and alcohol consumption was higher among individuals
      with high SES, while low SES was associated with alcohol abuse and addiction,
      although the evidence was less conclusive. Smoking was more frequent among young
      people with high SES, but in adults it was more common with low SES. Illicit drug
      use was more frequent among adults (but not adolescents) with low SES.
      Prescription drugs tended to be consumed by adults and adolescents with higher
      SES. Use of solvents was more frequent among low SES adolescents. The studies'
      observed trends and methodological aspects are also discussed.

PMID- 17546319
TI  - [Adolescence and mental health: a review of the Brazilian literature].
AB  - The objective of this work was to review the Brazilian scientific literature from
      1995 to 2005 on mental health in adolescence, considering the priorities
      identified by the World Health Organization (depression, anxiety, substance
      abuse, behavioral disorders, eating disorders, psychosis, child abuse, and
      violence). 971 abstracts were identified in the LILACS, MEDLINE, INDEXPsi, and
      SciELO databases, using descriptors associated with the themes. After selection
      according to specified criteria, 267 abstracts were analyzed by year, focus,
      methodological design, and principal conclusions. A qualitative analysis was
      performed on the main findings. Brazilian publications in this area have
      increased in the last five years. The majority of the articles aimed to identify
      the problem, while a smaller proportion dealt with the development of
      intervention and prevention strategies.

PMID- 17546320
TI  - Child health and nutrition in the Western Brazilian Amazon: population-based
      surveys in two counties in Acre State.
AB  - The article presents prevalence rates for malnutrition, intestinal parasitic
      infections, anemia, and iron deficiency in under-five children in a population
      based cross-sectional survey performed in the urban area of two counties in the
      Western Brazilian Amazon, Assis Brasil (n = 200) and Acrelandia (n = 477).
      Available data included: (a) weight and height measurements, standardized as z
      scores using the 1977 NCHS reference population, (b) diagnosis of current
      intestinal parasitic infection, (c) blood hemoglobin levels, and (d) plasma
      ferritin and soluble transferrin receptor levels. Overall prevalence rates of low
      weight-for-height, low weight-for-age, and low height-for-age were 3.7%, 8.7%,
      and 7.5%, respectively, with similar figures in the two towns. Intestinal
      parasites were detected in 32.5% children; helminths were uncommon. Anemia and
      iron deficiency were diagnosed in 30.6% and 43.5% of the children, respectively.
      Evidence of anemia was found in only 47.6% of the children with depleted iron
      reserves, indicating that hemoglobin measurement alone would severely
      underestimate the magnitude of iron deficiency in this population. In both towns,
      anemia and malnutrition were significantly more prevalent among children in the
      lowest socioeconomic stratum.

PMID- 17546321
TI  - [Health resort, industrial city: urban space and health policy in Sao Jose dos
      Campos, Sao Paulo, Brazil].
AB  - This study is part of the renewed theoretical and conceptual approach to space in
      health policies. The key potential of this approach lies in dealing with the
      organization of space as a product of relations between society and state power,
      influenced by the economy and enabled by politics. When understood as a social
      construction, such space provides the material basis for a historical narrative,
      allowing a better understanding of how policies are formulated and implemented in
      urban space. Based on this space, we investigate the policy governing the
      configuration of health services in the city of Sao Jose dos Campos, Sao Paulo,
      Brazil, during two different periods: the 1920s, in which the town became a
      health resort, and the early 1980s, when the municipal public health system was
      organized. A historical and geographic social reconstitution revealed both
      ambiguities and consistencies in a town whose health profile acquired the
      characteristics of an industrial city.

PMID- 17546322
TI  - Utilization of human papillomavirus testing for cervical cancer prevention in a
      university hospital.
AB  - This study aimed to evaluate the performance and cost of using polymerase chain
      reaction (PCR) and hybrid capture in the detection of cervical intraepithelial
      neoplasia (CIN) in patients with cytological abnormalities (ASCUS/low-grade
      squamous intraepithelial lesion--LSIL), and the feasibility of implementing these
      methods in Brazil's Unified National Health System (SUS). Colposcopy gave a
      negative predictive value of 92.86% and efficiency of 87.8% for diagnosing CIN.
      The sensitivity of PCR and hybrid capture for detecting CIN was 83.33% and
      66.67%, respectively, and the negative predictive value for diagnosing CIN2/CIN3
      was 100% and 94.74%, respectively. The annual cost for 80 patients was lower when
      all patients with ASCUS/LSIL were referred for colposcopy than when HPV testing
      was performed and those with positive results were referred for colposcopy.
      Therefore, at present, it is financially unfeasible for the National Health
      System to implement HPV testing to screen patients with cytological abnormalities
      (ASCUS/LSIL). However, considering that large-scale use might make such methods
      cheaper, PCR should be the chosen method, since it is less expensive, more
      sensitive, and has a high negative predictive value.

PMID- 17546323
TI  - [Factors associated with smoking cessation in two different adult populations
      (Bambui and Belo Horizonte Projects)].
AB  - The aim of this study was to verify smoking cessation rates and associated
      factors. The study was performed in Greater Metropolitan Belo Horizonte and the
      town of Bambui, both in the State of Minas Gerais, Brazil. Study participants
      included 13,261 and 1,018 adults (> 20 years), respectively, randomly selected
      among residents of each area. The smoking cessation rate was 40.6% (95%CI: 39.1
      42.3) in Greater Metropolitan Belo Horizonte and 38.8% (95%CI: 34.4-43.1) in
      Bambui. In Greater Metropolitan Belo Horizonte, smoking cessation showed an
      independent and positive association with age (> 40 years), schooling (4-7 and >
      8 years), number of chronic conditions (> 2), and number of medical visits in the
      previous year (1-3 and > 4), and a negative association with marital status
      (unmarried). Bambui showed an independent and positive association with age (> 40
      years) and a negative association with number of hospitalizations in the previous
      year (> 2). The heterogeneity of factors associated with smoking cessation made
      it difficult to identify vulnerable groups in order to target prevention
      strategies. Further research is important to elucidate this heterogeneity.

PMID- 17546324
TI  - [Variables associated with sedentary leisure time in the elderly in Campinas, Sao
      Paulo State, Brazil].
AB  - The objective of this study was to identify the prevalence of sedentary leisure
      time (no type of leisure-time exercise once a week or more) among the elderly in
      the city of Campinas, Sao Paulo State, Brazil, according to demographic and
      socioeconomic factors, other health-related behaviors, and the presence of
      morbidity. This was a population-based cross-sectional study with multiple-stage
      sampling. Data analysis considered the sample design. Prevalence of sedentary
      leisure time was 70.9%, and the prevalence ratio was significantly higher than
      1.0 for the elderly with lower socioeconomic status (1.31: 1.11-1.55), smokers
      (1.39: 1.23-1.57), those with common mental disorders (1.20: 1.04-1.39), and
      females (1.16: 1.00-1.35). Prevalence of walking was 23.5%, followed by fitness
      or bodybuilding programs (3.8%), and swimming or water aerobics (3.6%). The
      results show the need to develop global action for health-related behaviors in
      order for this approach to succeed. Attention should focus on the elderly with
      common mental disorders and those with lower socioeconomic status to ensure
      equity in health promotion practices.

PMID- 17546325
TI  - [Malaria in Amapa State, Brazil, 1970-2003: background and control].
AB  - The present study aims to describe malaria occurrence from 1970 to 2003 in the
      State of Amapa, Brazil. With positive films obtained from health agencies,
      temporal series on the annual parasite incidence--API (per 1,000 inhabitants)
      were elaborated, taking into account population data available from the Brazilian
      Institute of Geography and Statistics. The results showed an increase in API
      values, although non-linear, related to the rapid population growth associated
      with regional economic and social development during the period, ranging from
      15.1 in 1970 to 74.0 in 2000. Reversing this trend, a decrease appeared from 2001
      onward, reaching a reduction of 50% in 2002. The results showed an increase in
      API values from 1970 to 2000, consistent with the incidence profile for malaria
      occurrence in the Amazon. A reduction in API was observed by 2002, reaching the
      goals set by the current control program.

PMID- 17546326
TI  - [Results of childbirth care at a birthing center in Belo Horizonte, Minas Gerais,
      Brazil].
AB  - This was a descriptive and retrospective study of 2,117 deliveries from January
      2002 to July 2003 at the Dr. David Capistrano da Costa Filho Birthing Center in
      Belo Horizonte, Minas Gerais, Brazil. Widespread questions have been raised
      concerning the quality of services provided at birthing centers by obstetric
      nurses. The results of the current study were: 11.4% maternal transfer rate; 2.2%
      cesarean sections; 1.2% neonatal ICU admissions; and 1% 5-minute Apgar scores
      below 7. Delivery dystocia and the request for epidural anesthesia were the main
      reasons for maternal transfer, and respiratory distress was the main cause of
      neonatal ICU admission. Corrected neonatal mortality was 2 per 1,000 live births.
      The results at this birthing center did not differ significantly from those in a
      review of the international literature. The most striking finding was the low
      cesarean rate. Comparative studies and more comprehensive national data on low
      risk gestations are needed.

PMID- 17546327
TI  - [Prevalence of overweight and obesity and associated factors among schoolchildren
      in a southern Brazilian city].
AB  - This cross-sectional study aimed to determine the prevalence of overweight and
      obesity in a group of 11-13-year-old schoolchildren in Capao da Canoa, Rio Grande
      do Sul State, Brazil, and to investigate the association with possible risk
      factors for excess body weight. The sample was stratified, proportional to the
      number of pupils in each school. Nutritional status was assessed by body mass
      index (BMI) cutoffs according to age and gender as proposed by Cole et al.
      (2000). Socioeconomic, demographic, genetic, and behavior variables were
      analyzed. 719 children from 11 schools were interviewed, of whom there were 541
      (75.2%) with normal BMI, 153 (21.3%) with overweight, and 25 (3.5%) with obesity.
      Statistically significant associations were found with type of school, parents'
      nutritional status, level of physical activity, and time of sedentary behavior.
      Prevalence of overweight and obesity in these schoolchildren was high (24.8%), in
      keeping with the literature, confirming the problem's magnitude and severity in
      Brazil.

PMID- 17546328
TI  - Institutional change and political decision-making in the creation of the
      Brazilian National Health Surveillance Agency.
AB  - This article examines the decision-making process that led to the creation of the
      Brazilian National Health Surveillance Agency (ANVISA) in 1999. The authors begin
      by discussing the history of the Agency's predecessor, the Health Surveillance
      Secretariat, and the need for its modernization to adjust the quality of the
      products under its control to domestic and international demands. From the
      theoretical perspective of neo-institutionalism, the article goes on to analyze
      the social and political context surrounding the debate on the proposed
      alternatives to adjust Health Surveillance to new rules in line with such
      requirements, focusing especially on the formulation of the new policy, the
      decision-making arena, and the actors with specific interests in the sector. The
      research drew on extensive documentary and media material, plus interviews with
      key actors. The article concludes that a determinant factor for the creation of
      ANVISA was the favorable domestic political context, fostering a positive
      correlation of forces that (in an extremely short timeframe, 1998-1999) allowed
      the creation of the first regulatory agency in the social policies area in
      Brazil.

PMID- 17546329
TI  - [Inequality and damaged teeth: oral sequelae from living in poverty in the Dende
      community, Fortaleza, Ceara, Brazil].
AB  - This anthropological study focuses on the experience of dental disease in the
      context of poverty in Northeast Brazil. For six months in 2004, ethnographic
      interviews, narratives, and participatory observation were conducted with 31
      residents of the low-income Dende neighborhood in Fortaleza, Ceara, and the
      results were analyzed using a hermeneutic-dialectic method. Precarious living
      conditions make healthcare a difficult priority. Even when individuals experience
      acute toothache, seeking dental care is perceived as a "luxury" rather than a
      citizen's right. Difficult access to services and poor-quality restorations favor
      tooth extraction as the most effective intervention. Local residents complain
      about their deteriorating oral health and seek help from substandard clinics,
      patronizing politicians, and traditional healers. In this context, dental disease
      differs according to social class, leaves the sequelae of inequality, jeopardizes
      self-esteem, and hinders social inclusion. Dealing with such inequality requires
      a deeper understanding of the social determinants of health, reducing injustices
      in access to quality care, eliminating stigma, and empowering community members
      to confront the structural forces affecting their lives.

PMID- 17546330
TI  - [Evaluation of a methodology for financial resources allocation in Brazilian
      health sector].
AB  - In the early 1990s, a group of British researchers developed a new methodology
      for healthcare resource allocation based on need. The methodology's main
      characteristics are to draw on the theoretical model for healthcare services
      demand and apply data on health services utilization to estimate needs-based use.
      The objective of the current study was to assess the applicability of this
      methodology for allocating Federal resources at the local level in Brazil. Data
      from all acute hospital admissions in 1999 came from the Inpatient Information
      System of the Unified National Health System (SUS). The country was divided into
      134 geographic areas. The statistical models tested to estimate needs-based use
      applied the following need variables: infant mortality rate; standardized
      mortality rate; illiteracy rate; proportion of households headed by women; and
      mean number of household members. All tested models showed negative regression
      coefficients, indicating that the methodology is inadequate for resource
      allocation based on need in places like Brazil with large social inequalities in
      healthcare utilization.

PMID- 17546331
TI  - [The Integrar Project: an evaluation of comprehensive health care services in
      Vitoria, Espirito Santo, Brazil].
AB  - This article describes an experience with the integration of various healthcare
      services, called the Integrar Project, in Vitoria, capital of the State of
      Espirito Santo, Brazil, and analyzes the project's contribution to the
      development of comprehensive healthcare practices. The case study used a
      qualitative approach and covered the period from 2000 to 2003, identifying the
      project's potential in the areas of maternal and child health, continuing health
      education, and the family health strategy, but also identified difficulties in
      establishing integrated treatment projects involving both the Family Health
      Program teams and the various medical specialties. To a major extent the work
      proposal failed to materialize, highlighting the need to review the strategy to
      include new forms of communications and developing greater formal cooperation,
      beyond the existing informal coordination between individuals, teams, or
      services, based on a contractual logic in public healthcare services. Standards
      and norms that are negotiated through dialogue and a management contract would
      allow the involvement of professionals in sharing common goals and changing work
      processes. Such changes would involve management tools and new values to ensure
      accountability.

PMID- 17546332
TI  - [Efficacy of iron supplementation with or without vitamin A for anemia control].
AB  - This study aimed to evaluate the efficacy of weekly iron supplementation with or
      without vitamin A in the treatment of iron deficiency anemia, using an
      experimental, randomized, non-placebo-controlled design in 1999. 267
      schoolchildren 6 to 14 years of age were randomized to two treatment groups: one
      group (144) received 200mg iron sulfate alone, with 40 mg of elemental iron,
      while the other (123) received the same iron supplementation dose plus 10,000 IU
      of vitamin A (both groups for 30 weeks). Final anemia prevalence was reduced from
      48.4% to 17.7% (p < 0.001) in the group receiving iron supplementation alone and
      58.1% to 14.3% (p < 0.001) in the group receiving iron plus vitamin A. There was
      no significant difference between the groups at the end of the study according to
      mean Hb (p = 0.355) and anemia (p = 0.479). There was a significant correction
      for iron deficiency anemia with weekly iron-alone supplementation, but with no
      additional advantage of vitamin A. New studies on the synergism between these two
      micronutrients are recommended.

PMID- 17546333
TI  - [Out-of-pocket drug expenditures by retirees and pensioners 60 years and older in
      Belo Horizonte, Minas Gerais, Brazil].
AB  - The aim of this study was to analyze the structure of private drug expenditures
      by individuals 60 years and older in Belo Horizonte, Minas Gerais, Brazil. The
      study population consisted of a representative sample of retirees under the
      National Social Security Institute (INSS) in the city of Belo Horizonte,
      interviewed through a household survey. Monthly out-of-pocket drug expenditures
      were calculated, and a drug cost structure analysis was performed according to
      drug characteristics. 667 elders answered the survey. Mean drug expenditures per
      month were US$ 38.91. The therapeutic groups representing the majority of drug
      expenditures were: cardiovascular system (26%), nervous system (24%), and
      digestive/metabolic system (15%). Considering drug registration categories, brand
      name drugs accounted for the majority of expenditures (54%). The results of this
      study can support policies to improve both access to medicines and overall health
      conditions for the Brazilian elderly population.

PMID- 17546334
TI  - [Hearing screening in a public hospital in Belo Horizonte, Minas Gerais State,
      Brazil: hearing impairment and risk factors in neonates and infants].
AB  - The objective of this study was to estimate the prevalence of hearing impairment
      in children in a public hospital in Belo Horizonte, Minas Gerais, Brazil, and to
      investigate the association with risk factors described in the literature. This
      study was cross-sectional and retrospective and analyzed 798 newborns and infants
      evaluated in the Universal Neonatal Hearing Screening Program from June 2002 to
      December 2003. The risk factors established by the Joint Committee on Infant
      Hearing in 1994 and Azevedo in 1996 were studied, besides prematurity. Prevalence
      of hearing impairment was 1.8% (15 cases). A multivariate logistic regression
      analysis was used to verify associations between risk factors and hearing
      impairment, showing a significant statistical association (p < 0.05) between
      hearing loss and suspicion of hearing loss by relatives, hyperbilirubinemia
      (serum level requiring exchange transfusion), ototoxic drugs, and low birth
      weight. A significant prevalence of hearing impairment in neonates and infants
      was confirmed. Attention should thus be focused on risk factors for hearing
      impairment, using hearing programs that ensure prevention, early detection, and
      intervention.

PMID- 17546335
TI  - [Anthropometric assessment of Kamayura adolescents in the Upper Xingu, Central
      Brazil (2000-2001)].
AB  - Despite the proximity between indigenous groups in the Upper Xingu Region and
      Brazilian national society, studies have shown adequate weight-for-height and low
      height-for-age in indigenous children. Little is known about the nutritional
      status of indigenous adolescents. The present study aimed to evaluate the
      nutritional status of Kamayura adolescents. Anthropometric variables were
      collected from a sample of 65 adolescents (31 males and 34 females). Mean height
      was lower than both that of the Brazilian National Survey on Health and Nutrition
      and the reference population of the U.S. National Center for Health Statistics.
      There was a high rate of overweight in both males (38.7%) and females (23.5%),
      and one female adolescent was obese (2.9%). No overweight adolescent presented
      both the triceps and subscapular skinfolds above the 90th percentile. There were
      no cases of nutritional deficit among either male or female adolescents. Despite
      the high prevalence of overweight, the nutritional status of these adolescents is
      adequate, since the group presents low adiposity.

PMID- 17546336
TI  - [Psychiatric reform and substitutive mental health practices: an institutional
      reading of an experience at a psychosocial care center].
AB  - This article discusses the development of mental health care services based on
      the Anti-Asylum Movement. Drawing on contributions from psychoanalysis and social
      psychology, the study analyzes the conflicts and dilemmas arising in a
      Psychosocial Care Center (NAPS) in Santos, Sao Paulo, Brazil. This study is part
      of Master's degree research at the Social and Occupational Psychology Department,
      Institute of Psychology, University of Sao Paulo. Semi-structured interviews were
      used with workers at the NAPS. According to the interviews, the transformation of
      the mental health care model mobilizes psychological issues among the workers.
      Various conflicts and anxieties were observed in relation to changes in the
      institutional support provided by the NAPS over time. The article analyzes
      difficulties in dealing with differences in the team or feelings of abandonment
      resulting from changes in the local administration in the interface between
      subjects and the institution.

PMID- 17546337
TI  - [Opportunities in the pharmaceutical industry and the local development logic
      based on the Brazilian biomes: the basis for a national policy discussion].
AB  - This study discusses new concepts in the technological development of plant
      derived medicines and their relevance to public health, highlighting
      opportunities in the pharmaceutical market both for the production of herbal
      medicines and the development of new drugs based on plant substrates and
      molecules. Recent theoretical and scientific premises for the socioeconomic
      development of the "Knowledge Age" (considering local production arrangements and
      systems) could guarantee a competitive advantage for the sector, given the
      exuberant flora and biodiversity in the various Brazilian biomes.

PMID- 17546338
TI  - [Occupational risks for laryngeal cancer: a case-control study].
AB  - The most solidly established risk factors for laryngeal cancer are tobacco and
      alcohol. As for occupational factors, the only established carcinogen is exposure
      to strong inorganic acid mists. However, asbestos, pesticides, paints, gasoline,
      diesel engine emissions, dusts, and other factors have been reported in the
      literature as occupational agents that increase the risk of laryngeal cancer. A
      hospital-based case-control study was conducted to investigate occupational risk
      factors for laryngeal cancer. Detailed data on smoking, alcohol consumption, and
      occupational history were collected for 122 laryngeal cancers and 187 controls
      matched by frequency (according to sex and age). Laryngeal cancer was associated
      with exposure to respirable free crystalline silica (OR = 1.83; 95%CI: 1.00
      3.36), soot (from coal, coke, fuel oil, or wood) (odds ratio - OR = 1.78; 95%
      confidence interval - 95%CI: 1.03-3.03), fumes (OR = 2.55; 95%CI: 1.14-5.67), and
      live animals (OR = 1.80; 95%CI: 1.02-3.19).

PMID- 17546339
TI  - [Test-retest reliability of self-perceived oral health in an adult population in
      Rio de Janeiro, Brazil].
AB  - This study evaluated the test-retest reliability of a single item, namely self
      perceived oral health, included in a questionnaire applied in a longitudinal
      study (the "Pro-Saude" or Pro-Health Study, 2001). The questionnaire was applied
      twice in a sample of 101 employees at a State university in Rio de Janeiro,
      Brazil. Self-perceived oral health was based on a single item, with five choices,
      ranging from "very good" to "very bad". Agreement was estimated using weighted
      kappa statistics and stratified according to gender, age, income, and schooling.
      Overall kappa coefficient was 0.80. Higher values were found in women (k = 0.84),
      young adults (k = 0.85), subjects with medium-level schooling (k = 0.86), and
      those earning more than six times the minimum wage (k = 0.91). Lower kappa
      estimates were obtained for individuals over 40 years of age (k = 0.67 for 40-49
      years and k = 0.69 for > 50). The reliability of the single item "self-perceived
      oral health" varied from "considerable" to "almost perfect" in all population
      strata, suggesting that this item can be used in future analyses in the scope of
      the "Pro-Saude" Study.

PMID- 17546340
TI  - Giardia duodenalis infection: risk factors for children living in sub-standard
      settlements in Brazil.
AB  - The objective of the present study was to characterize Giardia duodenalis
      infection among children living in sub-standard settlement areas in the
      municipality of Juiz de Fora, Minas Gerais State, Brazil. The cross-sectional
      epidemiological study included 590 children from 1 to 5 years of age. Data were
      collected from one child per selected family through home interviews with the
      parent or guardian and parasitological examination of stool samples. Thirty-one
      putative risk factors concerning family structure, socioeconomic status, and
      environmental factors were analyzed by multivariate logistic regression.
      Prevalence of G. duodenalis infection was 18% (106 children). Four potential risk
      factors were heavily associated with G. duodenalis infection: number of under
      five children in the same household, index child's birth order, existence of a
      bathroom in the home, and drinking water source.

PMID- 17546341
TI  - [A paradigm for understanding and treating psychiatric illness].

PMID- 17546342
TI  - [Depression and stress: is there an endophenotype?].
AB  - OBJECTIVE: To review the new findings about stress, hypothalamic-pituitary
      adrenal axis and depression trying to explain a possible endophenotype prone to
      depression. METHOD: Nonsystematic review of the literature based on the
      endophenotype hypothesis. RESULTS: Depression is linked to hypercortisolemia in
      many patients, but not all patients present these hypothalamic-pituitary-adrenal
      axis dysfunction. The dexamethasone suppression test is not the most accurate
      test to measure the hypothalamic-pituitary-adrenal axis function, and its use in
      the first studies published probably jeopardized the results. Hypercortisolemia
      frequently occurs in patients with severe depression, melancholic, either
      psychotic or nonpsychotic type; it is linked to the presence of a polymorphism in
      the promoter of the serotonin transporter gene, with a history of childhood abuse
      or neglect, or other significant stressful experiences like the loss of a parent
      during childhood and temperament leading to alterations in the response to
      stress. CONCLUSIONS: The alterations of the hypothalamic-pituitary-adrenal axis
      depend on many factors like severity and type of depression, genotype, history of
      exposure to stress, temperament, and probably resilience. All these factors
      together result in an endophenotype thought to be prone to depression.

PMID- 17546343
TI  - [Overlap between atypical depression, seasonal affective disorder and chronic
      fatigue syndrome].
AB  - OBJECTIVE: We reviewed previous studies that have described an association
      between abnormal functioning of the hypothalamic-pituitary-adrenal axis and
      depression. In addition to melancholic depression, a spectrum of conditions may
      be associated with increased and prolonged activation of the hypothalamic
      pituitary-adrenal axis. In contrast another group of states is characterized by
      hypoactivation of the stress system, rather than sustained activation, in which
      chronically reduced secretion of corticotropin releasing factor may result in
      pathological hypoarousal and an enhanced hypothalamic-pituitary-adrenal negative
      feedback. Patients with atypical depression, seasonal affective disorder and
      chronic fatigue syndrome fall in this category. METHOD: The literature data on
      the overlap between the key-words were reviewed, summarized and discussed.
      RESULTS: Many studies suggest that these conditions themselves overlap
      biologically, showing hypofunction of central corticotropin releasing factor
      neuronal systems. CONCLUSIONS: Therefore, in the real world of clinical practice,
      patients often present in a grey area between classical idiopathic fatigue and
      early chronic atypical depression and/or seasonal depression. This underscores
      the potential common biological links underpinning common symptom clusters not
      only between depression (atypical and seasonal) and chronic fatigue syndrome, but
      also other conditions characterized by the hypothalamic-pituitary-adrenal axis
      mainly diminished the corticotropin realising factor activity.

PMID- 17546344
TI  - [Brain-immune interactions and implications in psychiatric disorders].
AB  - OBJECTIVE: This review will focus on the role of cytokines in the central nervous
      system and its implications to depressive disorder. We will then discuss the main
      findings of cytokine measurements in patients with major depressive disorder.
      METHOD: We searched Pubmed for studies published from 1999-2007, using the
      keywords depression and cytokine; and depressive disorder and cytokine. We have
      focused on pro-inflammatory cytokine measurements in patients with depression
      syndrome using DSM-criteria. RESULTS: Several lines of evidence suggest that
      cytokines have effects on depression, such as the induction of sickness behavior;
      clinical conditions related to cytokines that also overlap depressive symptoms;
      and immunotherapy that can lead to depressive symptoms attenuated by
      antidepressant treatment. Finally, patients with depression exhibit increased
      levels of pro-inflammatory cytokines, although conflicting results have been
      described. CONCLUSION: Cytokines may play a role in the pathophysiology of some
      cases of depression, although a causal link has not been established yet. Further
      longitudinal studies are needed to determine patterns of cytokine in patients
      with major depressive disorder, taking into account confounding factors closely
      associated with the activation of pro-inflammatory cytokines. In addition,
      simultaneous measurements of multiple biomarkers could provide critical insights
      into mechanisms underlying major depressive disorder and a variety of common
      cytokine-related diseases.

PMID- 17546345
TI  - [Anxiety, panic and the hypothalamic-pituitary-adrenal axis].
AB  - OBJECTIVE: This article focuses on the differential activation of the
      hypothalamic-pituitary-adrenal axis in generalized anxiety disorder and panic
      disorder. METHOD: The results of recently reported reviews of the literature are
      summarized and discussed. RESULTS: The results of experimental studies that
      assayed adrenocorticotropic hormone, cortisol and prolactin show that real-life
      panic attacks, as well as those induced by selective panicogenic agents such as
      lactate and carbon dioxide, do not activate the hypothalamic-pituitary-adrenal
      axis. Agonists of the cholecystokinin receptor B such as the cholecystokinin-4
      peptide and pentagastrin increase stress hormones regardless of the occurrence of
      a panic attack and, thus, seem to activate the hypothalamic-pituitary-adrenal
      axis directly. The benzodiazepine antagonist flumazenil does not increase stress
      hormones, but this agent does not reliably induce panic attacks. Pharmacological
      agents that increase anxiety in both normal people and panic patients (caffeine,
      yohimbine, serotonergic agonists) raise stress hormone levels. CONCLUSIONS: In
      addition to the differences in symptomatology and pharmacological response,
      generalized anxiety disorder and panic disorder affect stress hormones in
      distinct ways. While anticipatory anxiety and generalized anxiety disorder
      activate both the hypothalamic-pituitary-adrenal and the sympathoadrenal axes,
      panic attack causes major sympathetic activation, but has little effect on the
      hypothalamic-pituitary-adrenal axis.

PMID- 17546346
TI  - [Immune outcomes of sleep disorders: the hypothalamic-pituitary-adrenal axis as a
      modulatory factor].
AB  - OBJECTIVE: To review the literature on the interaction between sleep and the
      immune system. METHOD: A search on Web of Science and Pubmed database including
      the keywords sleep, sleep deprivation, stress, hypothalamic-pituitary-adrenal
      axis, immune system, and autoimmune diseases. RESULTS: On Web of Science, 588
      publications were retrieved; 61 references, more significant and closer to our
      objective, were used, including original articles and review papers. CONCLUSION:
      Sleep deprivation and immune system exert a bidirectional influence on each
      other. Since sleep deprivation is considered a stressor, inasmuch as it induces
      elevation of cortisol or corticosterone levels in humans and rodents,
      respectively, and given the well-known immunosuppressive effect of
      glucocorticoids, we propose that increased activation of the hypothalamic
      pituitary-adrenal axis is a major mediator of the immune alterations observed in
      patients with insomnia or in sleep deprived subjects.

PMID- 17546347
TI  - [Psychoneuroendocrinology of posttraumatic stress disorder].
AB  - OBJECTIVE: To review the literature on neurobiological findings related to
      hypothalamic-pituitary-adrenal axis dysfunctions associated with posttraumatic
      stress disorder. METHOD: The relevant scientific findings were described
      according to the date of publication and the characteristics of the studies:
      preclinical studies, studies on early life violence as a risk factor, and
      clinical findings related to patients diagnosed with posttraumatic stress
      disorder. RESULTS: A rich literature on hypothalamic-pituitary-adrenal axis
      dysfunctions and posttraumatic stress disorder was found. Neurobiological
      findings showed that posttraumatic stress disorder is associated with
      hypothalamic-pituitary-adrenal axis dysfunctions and other brain-related
      structures: prefrontal cortex, hippocampus, and amygdala. Posttraumatic stress
      disorder patients have low plasma levels of cortisol and present increased
      responsivity of glucocorticoid receptors, suggesting that the inhibition of
      negative feedback plays a significant role in the disorder pathology. Preclinical
      studies using animal models of maternal deprivation showed that depending on the
      moment the trauma occurred during the development, different hypothalamic
      pituitary-adrenal axis dysfunctions were produced. Clinical studies showed that
      early life stress is related to the development of psychopathologies during
      adulthood. CONCLUSIONS: There is robust evidence of hypothalamic-pituitary
      adrenal axis dysfunctions related to posttraumatic stress disorder, and the
      mechanisms underlying this association are being better understood.

PMID- 17546348
TI  - The innovative and enterprising course of the Latin American Journal of Nursing
      and the adoption of an internationalization policy.

PMID- 17546349
TI  - Nurses' visibility according to the perceptions of the communication
      professionals.
AB  - This study aimed to further our understanding of the social representations of
      nurses and the nursing profession by communication professionals, since they are
      intermediates in the decoding of imaging and written representations about
      society. METHOD: this is a qualitative study, based on the social representation
      theory of Moscovici. Five communication professionals working on radio,
      television, written press, advertising and events were interviewed. Results
      suggest 1) ignorance about the nurse's field of work, job market and nursing
      profession categorization. 2) nurses' invisibility before the media and society
      and 3) nurse's own responsibility to obtain professional recognition and
      visibility. Participants in this study pointed two essential processes for
      building a more coherent image of nursing and nurses: 1) exposing the profession
      primarily before the media, which ignores its potentialities, and 2) through the
      media in order to reach the population in general.

PMID- 17546350
TI  - The health-illness care process and the logic of the nurse's work in the ICU.
AB  - The present study aims to learn the health production logic in the ICU based on
      the discourse defended by nurses and on the professional practice that is
      recognized by the relatives accompanying the hospitalized patients. This is a
      qualitative and dialectic investigation performed with seven nurses and five
      relatives in an ICU for adults of a teaching hospital in Santa Catarina. The
      theoretical-philosophical referential was based on Marxist and Gramscians
      readings. The results show that the logic of the health production in the ICU is
      inserted in a dialectic rhythm of autonomy, dependence and co-responsibility for
      the care. We understand that this reality can demonstrate the need to rethink the
      knowledge and practices to promote the constant re-formularization and
      transformation of the assistant context of intensive care.

PMID- 17546351
TI  - Perceptions of nursing undergraduate students concerning the human dimension in
      the learning process.
AB  - This study aimed to identify and interpret the perceptions presented by
      undergraduate students of a Nursing course after internship in Mental Health.
      Twelve nursing undergraduate students at the Nursing School of ABC Foundation -
      Santo Andre, Sao Paulo, Brazil were interviewed. These interviews using a semi
      structure script were performed and recorded in August 2004. Through Content
      Analysis, thematic modality, four categories were identified, 1. mental health:
      providing understanding of the other; 2. respect for the human being: the
      importance of listening, 3. mental health: contributing for a contextualized view
      of the patient and 4. nursing graduation: undesirable "signs and symptoms" of the
      profession. The analysis and the discussion of these categories suggest the
      possibility of teaching based on the human condition. Thus, we support the idea
      of new research been carried out, considering that the Mental Health discipline
      must be valued in the Political and Pedagogical projects of the Nursing
      Undergraduate Courses.

PMID- 17546352
TI  - Group therapy with nursing students during the theory-practice transition.
AB  - This study aimed to verify whether the intervention of short term groups could
      provide nursing students means to cope with stress, typical of the transition
      process from the theoretical to the practical learning. Participant observation
      was used, allowing 12 students in the discipline Fundamentals II, to express
      their anxieties and anguish towards the new and future role of taking care of
      other people's health. Results suggest that higher nursing education institutions
      should consider the group technique not only as a support resource, but also as a
      didactical resource in their curricula. At a time when educational reforms are
      discussed, is important to bear in mind that any planned changes will have an
      effect not only in technical terms but will also affect the human being.

PMID- 17546353
TI  - Characterization of the structure for medication preparation in teaching
      hospitals: factors that interfere with the quality of care.
AB  - This article describes the physical environment, material and human resources of
      the structure for the preparation of medicaments. It is an exploratory
      descriptive study. Data were collected through scripts structured for observation
      and interview carried out with a sample of 92 (76%) nurse auxiliaries and all
      nurses of, two hospitals in Recife, PE, Brazil. Results showed that the
      environment in which medication is prepared is in disagreement with current
      legislation, the available materials need to be reviewed and professionals need
      to get their knowledge updated. It is concluded that the structure in the system
      of medication is essential and the factors pointed out in the study interfere
      with the quality of the process of medication.

PMID- 17546354
TI  - Women's social space and the reference for breastfeeding practice.
AB  - This study aimed to identify agents or institutions taken as reference by women
      when breastfeeding. A qualitative study was carried out on 20 primiparous who
      were assisted, for reasons not related to breastfeeding, in the five health
      services selected by this study. Data were collected by semi-structured
      interviews carried out in the participants' households and were analyzed by
      content analysis in the thematic mode. We identified that health professionals
      play a standardize role of breastfeeding based on scientific knowledge. In the
      daily breastfeeding routine, the family is the first reference for women,
      transmitting beliefs, habits and behaviors. We believe in the valorization of the
      family context by the health professional, in which actions and interactions in
      the breastfeeding issue are developed in order to constitute the foundations for
      a new care model in breastfeeding. This model should, therefore, consider the
      practice diversity, adapting actions to the multiple roles of being
      mother/fortress/wife/worker in the social context.

PMID- 17546355
TI  - The participation of parents in the care of premature children in a neonatal
      unit: meanings attributed by the health team.
AB  - This qualitative study aims to identify and analyze the meanings the health team
      attributes to the parents' participation in the care of premature children
      hospitalized at a public hospital. Data were recorded and collected through semi
      structured interviews performed with 23 professionals. The results show that
      parents' participation in the care of these children is still in an initial stage
      at the hospital's neonatal unit. However, there is interest from the health team
      to implement it because its importance is recognized in improving the clinical
      stability, the growth and development process of premature children. In addition
      to allowing for mother-child interaction and affective bonding, it prepares the
      mother for the child's discharge. The presence of the mother helps the nursing
      team by giving maternal care to the hospitalized child. On the other hand, the
      parents' presence interferes in the environment of the neonatal unit. It affects
      the work dynamics and creates insecurity among team workers, who feel supervised.
      Besides, there is concern regarding hospital infection. Thus, in accordance with
      other studies from different countries, these meanings entail reflections on the
      need to base the premature care in terms of collectively building a care
      philosophy that restores concepts of human rights, citizenship, bonding and
      mother-child attachment, pediatric psychology and also expands the concept of
      training for a participative health education.

PMID- 17546356
TI  - The interference of the care context with the visibility of the drug consumption
      by women.
AB  - In light of the increasing demand for female drug addiction care and its
      internationally acknowledged specificity, this qualitative study was carried out
      in Salvador, BA, Brazil, from October 2003 to September 2004. It aimed to
      investigate whether the context of care in which participants are inserted
      interferes with the visibility of female drug addiction. Participant observation
      and content analysis of 19 interviews performed with health care practitioners
      revealed that some aspects of female drug addiction were perceived differently
      according to the context of care (institution versus outdoors): demand, kind of
      drug used, age, social roles and partner's influence in the initiation and
      maintenance of drug use. Since the context of care impacts the health care
      practitioners' representation of female drug users which in turn can affect the
      strategies devised for their care, we recommend that not only the contexts of
      care within the studied unit should be articulate, but these contexts with those
      from other health services as well.

PMID- 17546357
TI  - The experience of a woman working in nursing suffering from De Quervain's
      disease.
AB  - This is a case study with a phenomenological approach on the experience of a
      woman who works in nursing and suffers from the de Quervain's disease, an osteo
      muscular disorder related to working conditions. This study aimed to understand
      what means to be a woman working in nursing and suffering from an osteo-muscular
      disorder related to working conditions through a worker of the Material and
      Sterilization Center of a private hospital. The philosophical referential from
      Martin Heidegger was used for the comprehensive analysis of the statement in
      question. The analysis revealed that the physiopathological process of the de
      Quervain's disease caused changes in the worker's life, characterized by painful
      manifestations and especially by physical limitations, which generate a
      multiplicity of feelings. Anguish is present in the process of accepting the
      disease, when the worker perceives the fragility of her existence and recognizes
      herself as the one responsible for her own care, reaching authenticity and
      transcending the disease.

PMID- 17546358
TI  - The vulnerability of nursing workers to tuberculosis in a teaching hospital.
AB  - This study aimed to identify aspects that potentially increase the vulnerability
      of nursing workers to tuberculosis, through the verification of personal life,
      work and disease knowledge indexes. The sample is composed of 81 nursing workers
      involved with assistance in the night and day shifts at USP Teaching Hospital,
      who answered a questionnaire about life and work habits. The sample aggregated
      the indexes that increase vulnerability to tuberculosis: long professional
      experience in hospitals and work load longer than 12 hours. Data show that
      nursing auxiliaries and workers from the night shift in general have a higher
      number of vulnerability indexes.

PMID- 17546359
TI  - Psychosocial and behavioral factors associated to STD/AIDS risk among health
      students.
AB  - This study aimed to identify and compare psychosocial and behavioral factors
      associated to STD/AIDS risk among students enrolled in the first and last years
      of the Nursing and Medical Undergraduate Programs at State University of
      Londrina. A convenience sample was selected from 263 enrolled students, and the
      183 students who were sexually active (70.4%) had their data assessed. The Aids
      Risk Reduction Model framework was used to design the questionnaire in which a 5%
      statistical significance level was considered. Some risk factors were identified
      such as the perception of invulnerability, multiple sexual partners, consumption
      of alcoholic beverages before intercourse, and the discontinuous use or no use of
      condom. The risk factors are common both to the freshman and senior students,
      with no significant differences related to the passage of time or to the
      students' higher educational level. Senior students tend to be monogamous which
      makes them feel safer and decrease the use of condom with their sexual partners.

PMID- 17546360
TI  - Domestic violence: from the visible to the invisible.
AB  - This study aimed to identify and analyze notifications of domestic violence
      against children registered at the Regional Health Services in Guarulhos, Sao
      Paulo, Brazil; the limitations imposed to health professionals' actions and the
      meaning of domestic violence against children in the health professionals'
      routine. The notifications registered between 2001 and 2002 were characterized in
      order to better understand this reality and also to support the collected data
      through the qualitative approach. There is a predominance of negligence cases
      45%, while 26% of the notifications related to physical violence and 14% to
      suspected sexual violence. Social workers registered the highest number of
      notifications, 46%. Based on the social agents' discourse, we identified two
      empirical categories: "interfaces of the violence" and "fear".

PMID- 17546361
TI  - Complementary feeding practices to children during their first year of life.
AB  - This study aimed to investigate complementary feeding practices during children's
      first year of life in Botucatu, SP, Brazil. Practices were described according to
      the age range and the breastfeeding (BF) practice. Data were collected during a
      multi-vaccination campaign through the interview of 1,238 individuals who
      accompanied children younger than one year old being vaccinated. Differences
      associated with the BF situation were identified by the chi-square test and
      Fisher's exact test. The early introduction of complementary food was observed,
      which led to the low frequency of exclusive breastfeeding (36.9% <4 months).
      Children younger than 4 months old consumed tea (30.7%); children between 4 and 6
      months old consumed fruits (54.1%), soups (39.9%) and home-made food (19.2%).
      Juice was offered only to 15.2% of children younger than 4 months old who were
      completed weaned, 60% of the children was offered water. Data show that the
      consistence of the food consumed was inappropriate: children between 6 and 8
      months old were offered the family's regular food (48.8%) and children older than
      8 months (71.6%) were offered soup. Therefore, interventions focused on
      complementary feeding are justified on the city.

PMID- 17546362
TI  - Playing in the waiting room of an infant outpatient clinic from the perspective
      of children and their companions.
AB  - Playing is one way children use to communicate with the world that surrounds
      them. This descriptive-exploratory study aimed to understand the experience of
      playing for children and their companions in an outpatient waiting room. We
      performed semi-structured interviews with 12 children and those responsible for
      them. In the data analysis, three themes were identified: waiting time: "there is
      no other way, you have to wait"; using the time to play: turning the clinic into
      a more pleasant space; and the toy as a relations mediator. Playing is revealed
      to be an effective pediatric nursing intervention strategy in helping the child
      to overcome barriers imposed by the assistance. This resource favors the
      communication process among children, companions and professionals and, thus,
      greatly contributes to improve the care delivery.

PMID- 17546363
TI  - Evaluation of the growth percentiles of children with congenital heart disease.
AB  - The purpose of this study was to evaluate the correlation between anthropometric
      measures of children with congenital heart disease with percentiles that
      represent their growth indicators. Anthropometric evaluations of 135 hospitalized
      children with congenital heart disease were performed in a hospital specialized
      in cardiac diseases in Fortaleza, CE, Brazil. For the growth evaluation,
      percentiles of height by age, weight by height and weight by age were calculated.
      Children's average age was 4.74 months (+ 3.78) and 66.7% of the children were
      male. The medians of the three percentiles presented values below percentile 10,
      indicating a high proportion of values considered of risk. The subscapular
      thickness presented positive correlation with the three percentiles. The values
      of percentiles studied indicated growth delay.

PMID- 17546364
TI  - Family visitors and companions of hospitalized elderly and adults: analysis of
      the experience from the perspective of the nursing working process.
AB  - This is a qualitative study using Grounded Theory as the methodological reference
      and the Process of Work in Nursing as the theoretical reference in order to
      understand the role assumed by nurses regarding hospital norms and routines
      applied to family visitors and companions of adult and elderly patients in a
      teaching hospital. Data analysis identified the theme: defining the modality of
      family support during hospitalization. This theme aggregates two main categories:
      becoming the family visitor and becoming the family companion. Through the
      analysis, it could be observed how established rules, which aims at disciplining
      and developing an efficient work in the hospital, can expose the lack of autonomy
      in the work process to modify relations in this context and how the familiar
      appropriation, as part of the health team, is far from being considered in the
      institutions.

PMID- 17546365
TI  - The association between nursing diagnoses and the occurrence of falls observed
      among elderly individuals assisted in an outpatient facility.
AB  - This is an exploratory descriptive study with a quantitative approach, in which
      variables associated to the occurrence of falls observed in elderly assisted in
      an outpatient clinic are delineated from the nursing diagnoses. Data from the
      files of 490 elderly with age between 60 and 98 years old were investigated.
      Univariate and bivariate statistical analyses were performed (p <0,05). The
      dependent variable, occurrence of falls, was prevalent in 30% of the cases and
      occurred with more frequency among females. A positive and independent
      association with the following diagnoses of Nursing was found: loss of balance (p
      <0,001), high blood pressure (p <0,001), weakness (p <0,025) and urinary
      incontinence (p <0,025). No association was observed for: altered vision, altered
      audition, joints pain, altered march and postural hypotension. The study shows
      the importance of working issues related to the variables that presented positive
      association with the occurrence of falls in the nursing practice.

PMID- 17546366
TI  - Postoperative urinary retention: evaluation of patients using opioids analgesic.
AB  - The study aimed to determine the occurrence of urinary retention in patients
      using opioid analgesic and to describe the method used for vesical relief. A
      prospective and consecutive series of 1,316 patients undergoing surgery from
      September 1999 to April 2003 and using opioids post surgery were studied. From
      the 1,136 patients, 594 did not use urinary catheters pre-surgery. From these 594
      patients, 128 (22%) suffered post operative urinary retention. Urinary retention
      was significantly related to the use of continuous epidural analgesia (p=0.009).
      About 69% of patients experiencing urinary retention post surgery returned to
      spontaneous micturition following a single catheterization. The incidence found
      of urinary retention was similar to the literature, more frequent in men who
      received continuous epidural analgesia. The findings suggest orientation and
      careful nursing team observation of post operative micturition, emphasizing the
      intermittent aseptically catheterization for urinary retention in order to
      prevent potential complications of the urinary tract.

PMID- 17546367
TI  - Evaluation of social support among surgical cardiac patients: support for nursing
      care planning.
AB  - This descriptive and cross-sectional study aimed to measure social support among
      subjects hospitalized for surgical treatment of cardiac diseases and to verify
      the relations between social support and socio-demographic variables. Data were
      collected between May, 2004 and June, 2005. A total of 86 patients were studied,
      47 men, 58 married and the average age was 53 years old. Regarding social
      support, in an interval from 1 to 5, we found an average of 4.2+0.74 (interval of
      1.92 to 5) for the emotional support and 4.2+0.6 (interval of 2.3 to 5) for the
      instrumental support, which indicate high satisfaction and availability of
      received supports. We found weak but statistically significant correlations
      between instrumental and emotional supports and the participants' age and between
      instrumental support and years of education. We did not find any differences in
      the perception of social support in terms of participants' gender and marital
      status.

PMID- 17546368
TI  - Amputation in the perception of those who experience it: a study under the
      phenomenological.
AB  - This study aimed to understand the implications and feelings associated with the
      experience of amputation. The literature review allowed the knowledge of this
      phenomenon under several perspectives, besides the appropriation of some ideas of
      the philosopher Merleau-Ponty about body and perception. After this initial
      knowledge, interviews were performed with people who underwent amputation, by
      living in their world and listening to their statements. By sharing these
      moments, it was possible to understand meanings from the perspective of those who
      experience it, which led to six thematic categories. In addition to understanding
      those who underwent amputation in their context and in their essence, some facets
      of this phenomenon were revealed through the phenomenological referential.

PMID- 17546369
TI  - Health education: a strategy of care for the lay caregiver.
AB  - This article aimed to reflect about the importance of the role nurses perform in
      strategies of health education to lay caregivers, who are important actors in the
      health/disease process. It is a thematic reflection, built through bibliographic
      review, which discusses the role of lay caregivers in different stages of the
      life cycle. Considering the participation of lay caregivers in the Brazilian
      reality, strategies have been sought to include them in the health care, given
      the little attention Public Policies have given to them. Therefore, the nurses as
      health educators, must offer support to the lay caregivers helping them to choose
      among available alternatives, while delivering care, to not harm their own
      health. Concluding, health education can be an alternative to offer attention to
      the lay caregivers, while the nurse has important role in the development of
      alternatives.

PMID- 17546370
TI  - Educational settings in the management of patients with heart failure.
AB  - Congestive heart failure (CHF) presents, besides the magnitude of epidemiological
      data, relevant characteristics, including frequent hospitalizations caused by
      severe signs and symptoms, which should be studied to reduce the negative impact
      of the disease on the public health system. With the advent of several clinical
      trials in the area of CHF, the treatment has become more complex, with the need
      of a more organized structure to assist these patients. Education is considered
      essential to reduce morbidity and mortality. The setting, to begin or to continue
      the educational process, can be a hospital (hospitalization), outpatient clinic,
      home, a day-hospital or yet, a combination of these. The main researches in this
      area recognize and motivate an investigation of other paths to get better results
      in the pharmacological and non-pharmacological treatments. In this study we
      review recent data, approaching several educational settings in the management of
      patients with CHF.

PMID- 17546371
TI  - Palliative care to the cancer patient: reflections according to Paterson and
      Zderad's view.
AB  - This reflective study presents the approach of the Nursing Palliative Care to the
      cancer patient without therapeutic possibility according to the Paterson and
      Zderad's Humanistic Nursing Theory. The palliative care aims to provide the
      patient without therapeutic possibility and his family better quality of life.
      When the nurse, in addition to delivering palliative care to the cancer patient,
      uses the Humanistic Theory, (s)he starts to recognize each person as a singular
      existence. This recognition permits one to understand the person's meaning in the
      process of his(er) disease.

PMID- 17546372
TI  - Women's health education in undergraduate nursing courses.
AB  - This article aimed to analyze the Women's Health Education in the Nursing courses
      in Sao Paulo, SP, Brazil, characterizing faculty members and the pedagogical
      processes implemented. A questionnaire was carried out with 17 professors
      responsible for the teaching. It was possible to observe good qualification of
      the faculty members, in its majority with teaching experience superior to five
      years. In addition, most of the professors have teaching education with partial
      dedication to teaching and research or work per hour. The denomination "Women's
      Health Nursing Assistance" is adopted by the majority of courses. The pedagogical
      processes tend to extend conceptual references, keeping expositive classes as the
      main teaching strategy and written tests are the most applied evaluation method.
      The teaching of woman's health presents, therefore, a more critical perspective
      about woman's health with the participation of graduate professors and learning
      situations that integrate both the transmission and the active construction of
      knowledge.

PMID- 17546374
TI  - [Treatment of periodontal patients - current clinical concepts].
AB  - The main goal of the treatment of patients with periodontitis is to establish
      adequate infection control. To satisfy demands for acceptable aesthetics and
      chewing function with good long-term prognosis in patients with periodontitis
      requires the establishment of adequate infection control. Pocket instrumentation
      (scaling and root planing with or without flap elevation), combined with
      effective self-performed supragingival plaque control measures, constitutes the
      basic treatment modalities.

PMID- 17546375
TI  - [Detection of gingipian gene of Porphyromonas gingivalis in subgingival plaque].
AB  - PURPOSE: The purpose of this study was to detect two genes (kgp-cd and rgpB-cd)
      of Porphyromonas gingivalis in subgingival plaque, and determine the relationship
      between the two genes and the periodontal clinical indexes. METHODS: Eighty four
      subgingival plaque samples were included in this study. The extracted DNA was
      amplified with the primers designed to obtain the genes encoding the catalytic
      domain of kgp and rgpB (kgp-cd, rgpB-cd), and typing P.gingivalis into two
      genotypes. The relationship between different genotypes of P. gingivalis and the
      periodontal clinical indexes was statistically analyzed by SPSS11.5 software
      package for Student's t test and Chi-square test. RESULTS: The detection rate of
      type-A P.gingivalis (85.29%) was higher than that of type-B P.gingivalis
      (14.71%), P<0.05. Both probe depth and bleeding on probing had significant
      difference between different genotypes of P.gingivalis
      (PD:t=2.85,P<0.05;BOP:P<0.05). CONCLUSIONS: kgp-cd and rgpB-cd were related to
      pathogenicity of P.gingivalis.

PMID- 17546376
TI  - [Detection and significance of IL-1beta and MMP-8 in patients with periodontitis
      of whole unstimulated saliva].
AB  - PURPOSE: To detect the role of IL-1beta and MMP-8 by ELISA in whole unstimulated
      saliva of patients with different type of periodontitis and to determine whether
      they are possible specific biomarkers of periodontitis. METHODS: A total of 80
      saliva samples were collected from 28 GCP patients, 28 GAgP patients and 24
      healthy subjects. The levels of IL-1beta and MMP-8 were respectively measured by
      ELISA kits. The data were analysed statistically with one-way ANOVA. RESULTS: The
      mean salivary levels of IL-1beta in GCP group,GAgP group and control group were
      144.40 pg/ml+/-150.70 pg/ml+/-72.56 pg/ml+/-69.36 pg/ml and 65.96 pg/ml+/-71.18
      pg/ml respectively, There was no significance difference between the three groups
      (P>0.05); GCP and GAgP groups presented significantly elevated salivary levels of
      MMP-8 than that of the control group, which was (576.89+/-559.24) ng/ml,
      (420.93+/-533.73)ng/ml and (151.49+/-216.38) ng/ml respectively (P<0.05), while
      there was no significant difference between GCP and GAgP group (P>0.05).
      CONCLUSION: Salivary levels of MMP-8 may be a biomarker for diagnosis for
      periodontitis while IL-1beta needs to be further testified.

PMID- 17546377
TI  - [The influence of the try-in pastes on the colour of all-ceramic veneers].
AB  - PURPOSE: To study the influence of the try-in pastes on the color of all-ceramic
      veneers made by Ips-empress II system. METHODS: 50 discolored teeth were
      collected and restored with all-ceramic veneers. Five try-in pastes including A1,
      A3, transleucent(Trt), white opaque(WOT) and B0.5 opaque(B0.5),which were
      different in shade, were respectively used to try in before cementing. The color
      was measured by the ShadeEye, a digital colorimeter, and expressed in terms of 3
      coordinate values (L*,a*,b*) of the CIEL*a*b* system. Then the color
      differences(deltaEa*b*) of all-ceramic
      veneers[deltaEa*b*=(deltaL*(2)+deltaa*(2)+deltab*(2))(1/2)] as well as the value
      of L*deltaC(ab)[C(ab)=(a*(2)+b*(2))(1/2)] and H(ab)[H(ab)=arctan(b*/a*)]were
      calculated. Meanwhile,the thickness of the measurement point was measured and
      recorded. One-way ANOVA was used to analyze deltaEa*b* as well as L*,C(ab) and
      Hab. RESULTS: The average thickness of the ceramic was 1.088mm, and the colour of
      the veneers after try in with WOT paste and B0.5 paste performed a higher L*
      value than the other pastes (P<0.05).And the veneers also showed a higher C(ab)
      value after try in with WOT,B0.5 and A3 paste than the A1 and Trt paste (P<0.05).
      No significant differences were found in Hab value after these 50 veneers tried
      in with these five kinds of pastes. CONCLUSIONS: It's more advisable to choose
      the WOT or the B0.5 luting agent to cement the veneer when the abutment tooth is
      severely discolored, while the Trt or the A1 shade and A3 shade luting resin may
      be more appropriate if the abutment tooth doesn't discolor or a little compared
      with the adjacent tooth.

PMID- 17546378
TI  - [Preliminary study of the clinical indices for halitosis].
AB  - PURPOSE: To explore the possibility of using other clinical indices to detect
      halitosis in stead of organoleptic test(OST). MEATHODS: 56 medical students were
      chosen as the subjects. Spearman test and Pearson test were used to analyze the
      relationship between OST results and other indices. RESULTS: It was found that
      the value of volatile sulfur compounds (VSC) (r(Max)=0.537,P<0.01)
      rStable=0.572,P<0.01), pH of the saliva(r=0.344,P<0.01), cadaverine
      (r=0.352,P<0.01), OHI-S (r=0.323,P<0.05), colonies of facultative anaerobe from
      saliva(r=0.398,P<0.01) and tongue dorsum(r=0.293,P<0.05), colonies of anaerobe
      from tongue dorsum(r=0.473,P<0.01) correlated positively with OST score, but the
      coefficients were all low. CONCLUSION: It is not practical and feasible to
      replace OST with any other single index at present.

PMID- 17546379
TI  - [Treatment of chronic apical periodontitis teeth complicated by open apices with
      Vitapex in the adults].
AB  - PURPOSE: The aim of this study was to evaluate Vitapex (a premixed calcium
      hydroxide and iodoform paste) for treatment of chronic apical periodontitis
      complicated by incompletely developed apices in the adults. METHODS: 36 teeth
      with incompletely formed apices were selected. After the root canals were
      prepared and sterilized , Vitapex was used in the apexification. All the patients
      were followed-up clinically and radiographically 3 months and 10-18 months
      postoperatively. The root canal were then filled with Obtura II gutta-percha when
      the apical barrier could be detected. RESULTS: A radiographic evaluation showed
      that 7(19.4%) teeth completed root development and apical closure. 27 (75%) teeth
      could be detected apical barrier. 2 (5.6%) teeth were failed. The overall success
      rate was 94.4%. The average period of the whole endodontic treatment was 13.0
      weeks. CONCLUSION: Vitapex is a good material in the treatment of chronic apical
      periodontitis complicated by incompletely formed apices in the adults.

PMID- 17546380
TI  - [Evaluation of the clinical effects and scanning electron microscopic observation
      of different kinds of ultrasonic scaler used in subgingival scaling].
AB  - PURPOSE: To assess and compare the clinical effects of Odontogain and Prophy Max
      ultrasonic scaler used in periodontal treatment. METHODS: Twenty patients with
      chronic periodontitis were selected using both the Odontogain (group A) and
      Prophy Max (group B) ultrasonic scaler in a split mouth design. Six teeth of each
      patient were included in one group. The time used in each instrumentation was
      collected, and the periodontal indices (BOP,PD,CAL) were recorded before
      treatment, one month and two months after treatment, respectively. Meanwhile, 10
      extracted human single-rooted teeth were collected and divided randomly into A
      and B group. The root surface of the treated teeth were examined with scanning
      electron microscopy (SEM). The time used in each instrumentation was recorded.
      SAS6.12 software package was used for statistical analysis. RESULTS: Each
      periodontal index of group A and group B had improved significantly one and two
      months after subgingival scaling (P<0.01). The effect of the treatment of group A
      was better than group B, but there was no significant difference between them
      (P>0.05). For the time used on clinical treatment and extracted teeth , group A
      was significantly better than group B (P<0.01). It was observed from SEM that the
      root surfaces of both group A and B were smooth after scaling, and the remaining
      dental calculus of group A was less. CONCLUSION: The two kinds of ultrasonic
      scaler could improve the clinical indices in periodontal therapy. Odontogain
      ultrasonic scaler was more effective.

PMID- 17546381
TI  - [Effects of three caries removal methods on children's dental fear evaluated by
      physiological measure].
AB  - PURPOSE: To evaluate the effects of three caries removal methods on children's
      dental fear by physiological measure. METHODS: 90 children with caries lesions
      into dentin in primary molars were divided into three groups randomly:
      Chemomechanical carious removal group, atraumatic restorative treatment (ART)
      groups and traditional rotary instrument group. The baseline of blood pressure,
      pulse was recorded before the treatment. Then the blood pressure and the pulse of
      each subjects were measured 5, 10 and 15 minutes and at the end of the treatment
      respectively. The dental fear was evaluated by observing the trend of blood
      pressure and pulse in the process of the treatment, and the results were analyzed
      by SPSS11.5 software package, using one-way ANOVA and Student-Newman-Keuls
      methods to determine the effects of different caries removal methods on
      children's dental fear. RESULTS: The degree of dental fear in traditional
      drilling group was significantly higher than that in chemo-mechanical group and
      ART group. The difference of each index between rotary instrument group and ART
      group was significant at the first time-point from the beginning of the treatment
      (P<0.05), but not significantly between rotary group and chemo-mechanical group
      (P>0.05), and between ART and chemo-mechanical group. (P>0.05). At the second
      time-point, the difference of systolic blood pressure was significant between
      rotary group and chemomechanical group(P<0.05), and the same between rotary group
      and ART group (P<0.05), but not between ART and chemo-mechanical group (P>0.05),
      while the difference of the other index among the three groups was not
      significant(P>0.05). There was no significantly difference of each index among
      the three groups at the time-point afterwards(P>0.05). CONCLUSION: Compared to
      traditional caries removal method, chemomechanical technique and ART may decrease
      children's dental fear effectively.

PMID- 17546382
TI  - [The effects of dentists'performance on the clinical effects of root canal
      preparation].
AB  - PURPOSE: To evaluate the effects of dentists'performance on the clinical
      efficacies of root canal preparation. METHODS: 164 teeth, including 66 vital
      teeth and 98 necrotic pulp teeth , were divided into two groups in random. All
      the root canals were prepared using ProTaper nickel-titanium rotary by two
      dentists with junior senior qualification. The incidence of instruments fracture,
      endodontic interappointment pain (EIP) and successful rates of root canal filling
      of the two groups were compared by X(2) test with SAS 6.2 software package.
      RESULTS: Between the two groups, the difference of the incidence of instruments
      fracture in molar was significant (P<0.05). The incidence of EIP between the two
      groups had high significant difference (P<0.01); The difference of vital teeth
      and necrotic pulp teeth was significant (P<0.05) in junior dentist group. The
      successful rates of root canal filling had significant differences (P<0.05),
      especially in necrotic pulp molar teeth. CONCLUSION: Skilled and accurate
      operation can improve the clinical efficacies of root canal preparation.

PMID- 17546383
TI  - [Expression of Survivin and its significance in tongue squamous cell carcinoma].
AB  - PURPOSE: To investigate the expression of Survivin,one of inhibitors of apoptosis
      proteins(IAPs) in tongue squamous cell carcinoma(TSCC), and discuss its clinical
      significance. METHODS: Immunohistochemical staining was employed to detect the
      expression of Survivin in 10 normal lingual mucosal membranes, 13 highly
      differentiated SCCs,20 medium-differentiated SCCs and 12 low-differentiated SCCs.
      Data was analyzed with SPSS13 software package for nonparametric Kruskal-Wallis
      test and Mann-Whitney U test. RESULTS: The positive staining rate of Survivin in
      TSCC was 68.9%, and significantly higher than that in normal control group
      (P<0.01). Overexpression of Survivin was related to the pathological grade, TNM
      stage (P<0.05) and closely to lymph node metastasis of TSCC (P<0.01).
      CONCLUSIONS: The positive staining of Survivin increased in different grades of
      TSCC, and Survivin is relative to carcinogenesis, progression and prognosis of
      TSCC. It may be a new clinical therapeutic target for TSCC.

PMID- 17546384
TI  - [Preliminary clinical study on intrusion of overerupted molars with a removable
      appliance].
AB  - PURPOSE: To evaluate the clinical effect of molar intrusion with a removable
      appliance and determine its clinical value. METHODS: Seven patients were selected
      in the study.The clinical effect of intrusion was evaluated,the periodontal
      attachments and root resorption post-treatment were accessed by models,clinical
      examination, periapical radiograph analysis via CygnusRay2TM digital X-ray system
      pre and post-treatment.The data was analyzed using SAS6.12 software package.
      RESULTS: All the overerupted molars had been intruded successfully within an
      average time of 3.7 months.Pre and post-treatment model analysis demonstrated the
      maximum intrusion amount was 3.05mm,minimum 1.03mm and mean 0.58mm per
      month.Analysis of pre and post-treatment periapical radiographs and periodontal
      probing depth showed no significant difference in probing depth,distance from
      cemento-enamel junction to alveolar bone crest,mesial and distal tooth length
      between pre- and post- treatment (P>0.05). CONCLUSIONS: Molar intrusion with the
      removable appliance has a significant effect without apparent destruction of the
      periodontal tissue and root resorption.

PMID- 17546385
TI  - [Changes of aspartate aminotransferase and alkaline phosphatase activities in
      gingival crevicular fluid during rapid palatal expansion].
AB  - PURPOSE: This study was designed to examine the changes of aspartate
      aminotransferase (AST) and alkaline phosphatase(ALP) activities in gingival
      crevicular fluid (GCF) during rapid palatal expansion, and to explore the
      relationship between these changes and periodontal tissue remodeling. METHODS:
      Thirty-eight patients (aged 10.5 to 12.8years) who required opening of the
      palatal suture as the first stage of their orthodontic treatment were included
      and studied. The patients were divided into two groups: control group (18 cases)
      and experimental group (20 cases). GCF samples were collected at 6 observation
      periods with filter paper strips: before activation, 24 hours and 7 days after
      activation, 7 days, 14 days, and 28 days in retention. AST and ALP activities
      were determined by a full automatic biochemical analyzer, and the results were
      expressed as total AST and ALP activities. The data was analyzed with SAS (r)
      Proprietary Software Version 9.00 for paired t test and two-sample t test.
      RESULTS: AST activity was significantly elevated after 24-hour activation in the
      test group (P<0.05), but after 7-day activation in the control group (P<0.01).
      Both in the control and experimental group, AST activity remained high until 28
      day in retention (P<0.01). AST activity in the test group was significantly
      greater compared to the control group from 24-hour activation to 28-day in
      retention (P<0.05). ALP activity increased significantly from 7-day activation to
      28-day retention in the control and experimental group (P<0.01), and there was
      statistically significant difference between the control and the experimental
      group from 7-day to 28-day in retention (P<0.01). CONCLUSION: Our results suggest
      that AST and ALP levels in GCF may reflect the tissue remodeling which occurs in
      the periodontium during rapid palatal expansion to some degree.

PMID- 17546386
TI  - [Effect of two kinds of chewing gums on dental plaque pH].
AB  - PURPOSE: The aim of the study was to evaluate the change of plaque pH after
      chewing 2 kinds of gums. METHODS: The investigation consisted of 8 healthy
      subjects (aged 23-27 years, 4 males and 4 females) who refrained from
      toothbrushing for 24 hours before the test. The pH of dental plaque was measured
      using a Beetrode pH microelectrode before and after sucrose challenge with a 10%
      sucrose solutions at 5, 10, 15, 20 minutes as the baseline data. One week later
      the pH of dental plaque was measured again before the rinse and then the subjects
      rinsed with a 10% sucrose solutions. After 1 minute the sugar-free chewing gum
      was given and started to chew for 5, 10, 15, 20 minutes. The pH of dental plaque
      was measured at the same time on the non-chewing side. One week later the same
      test was carried out but the chewing gum was changed to tea polyphenol gum.
      Dental plaque pH value were analyzed by one-way ANOVA and SNK using SPSS 10.0
      software package. RESULTS: Compared with the baseline chewed either tea
      polyphenol gum or sugar-free gum could increase the plaque pH recovery due to the
      sucrose rinsing challenge and it could maintain the dental plaque pH above the
      resting value. There was no statistically significant difference between tea
      polyphenol gum and sugar-free gum (P>0.05). CONCLUSION: Both gums can increase
      the plaque pH and decrease the risk of caries.

PMID- 17546387
TI  - [The ultrastructure and activities of free radical scavenger in discolored
      gingiva adjacent to porcelain fused to metal crowns].
AB  - PURPOSE: This study was designed to study the discolored gingiva adjacent to
      porcelain fused to metal (PFM) crowns in terms of ultrastructure , SOD and GSH
      activities in 40 cases. METHODS: The discolored gingival ultrastructures were
      observed and metal X-ray energy level was analyzed;The activities of SOD and GSH
      were measured and compared with normal control by student's t test and one-way
      ANOVA with SPSS10.0 software package. RESULTS: The discolored gingival
      ultrastructure had changes compared with the normal gingiva. Nickel and chromium
      were not found in the particles through X-ray energy machine within the
      discolored gingiva adjacent to PFM crown. The activities of SOD and GSH in
      discolored gingiva were significantly different from control(P<0.05) and the
      values at 6 to 18 months were significantly different from those at other times.
      CONCLUSION: The ultrastructure underwent changes in discolored gingiva after PFM
      restoration; the activity of SOD and GSH in discolored gingiva changed to result
      in apoptosis, and discoloration.

PMID- 17546388
TI  - [The application of headgear in treatment of the upper crowding].
AB  - PURPOSE: To evaluate the treatment effect of headgear for distal movement of
      maxillary first molars to correct the crowding caused by molar anterior
      displacement. METHODS: 12 crowding cases were treated with headgear combining
      with fixed appliances if necessary. Cephalometric radiographs and casts were
      taken and analyzed before and after treatment. SPSS13.0 software package was used
      for paired-samples t test. RESULTS: The crowding of upper arch was significantly
      decreased (P<0.05), the amount of crowding decrease was from 3.0 mm to 6.0 mm,
      the average crowding decrease of 12 cases was 4.52 mm. The decrease was mainly
      due to the distal movement of the first upper molar, the amount of decrease of
      Ptm-U6 was from 1.2 mm to 3.5 mm, the average was 2.14 mm. CONCLUSION: Distal
      movement of the first upper molar by headgear is one of the effective way to
      solve the upper crowding.

PMID- 17546389
TI  - [Fabrication and clinical application of molar distal jet].
AB  - PURPOSE: To design a kind of appliance to open space for aligning cuspid which is
      buccally and gingivally malpositioned.This kind of appliance can also be used to
      open space for distal movement of the upper arch moderate protrusion. METHODS: At
      first, two bands of maxillary cuspids were made, then the two cuspid bands and
      additional two molar bands were put on the teeth respectively. After the
      impression was taken and poured, the molar distal jet was fabricated on the
      model. Finally, it was worn and one piece of coil was used to apply force to
      remove the molars distally. RESULTS: Four cases were treated using this
      appliance.Both molars were distally moved within three months, and the necessary
      space was gained for subsequent treatment. CONCLUSION: Maxillary molar distal jet
      is an effective appliance to open space and move the maxillary molars distally.

PMID- 17546390
TI  - [An experimental study on the relationship between the orthodontic tooth
      movements and menstrual cycle].
AB  - PURPOSE: The purpose of this study was to explore the relationship between the
      menstrual cycle and orthodontic tooth movement. METHODS: A Wistar rat model was
      established to apply orthodontic activation during different stages of the
      estrous cycle. The distances of the tooth movements were measured and the serum
      estradiol level was detected by radioimmunoassay. The data of each group was
      analyzed with SPSS11.0 software package for Student-Newman-Keuls(S-N-K)test and
      one way ANOVA test. And cosinor-rhythmometry method was used for chronobiologic
      analysis to show the rhythmic change of the serum estradiol level. RESULTS: There
      was a 5-day rhythm of the rat serum estradiol during the estrous cycle. The
      distances of orthodontic tooth movement were different at various stages. Teeth
      moved fastest in the estrus while the serum estradiol was lowest (P<0.05), the
      distance of tooth moved was (2.10+/-0.14)mm. And teeth moved slowest in the
      proestrus while the serum estradiol was highest (P+/-0.05), the distance of tooth
      moved was (1.79+/-0.03)mm. Totally, orthodontic activation increased the serum
      estradiol level without disturbing its fluctuating rhythm. CONCLUSION: It was
      inferred that female patients may have an optimal opportunity of orthodontic
      activation for rapid tooth movement, which should be applied on a few days before
      the menorrhea in order to move the teeth rapidly.

PMID- 17546391
TI  - [Construction and verification of the dual-promoter plasmid pCN-SSISG as bivalent
      anti-caries DNA vaccine].
AB  - PURPOSE: The aim of the study is to construct an anti-caries DNA vaccine with
      high immunogenicity due to its unique properties of being able to express target
      antigens both in eukaryotic and prokaryotic host cells and harboring two main
      virulence genes from caries pathogen Streptoccocus mutans (S. mutans). METHODS:
      The gene encoding glucan binding region (GBR) of glucosyltransferase-I (GTF-I)
      was amplified from the plasmid harboring the gtfB gene from S. mutans by PCR.
      Then the GBR gene that was upstream linked with tissue-type plasminogen activator
      signal peptide (tPA-SP) was directly cloned into the plasmid pCN-SSIE containing
      sSBR gene encoding tPA-SP and saliva binding region (SBR) of antigen protein I/II
      (AgI/II) from S. mutans. And finally the recombinant plasmid pCN-SSISG was
      analysed by DNA sequencing and endonuclearase digestion mapping. RESULTS: DNA
      sequencing and endonuclearase digestion mapping showed that the open reading
      frame (ORF) and the tPA-SP sequence of the recombinant plasmid pCN-SSISG were
      identical with the expectant ones. CONCLUSION: We have successfully constructed
      the dual-promoter bivalent recombinant plasmid pCN-SSISG.

PMID- 17546392
TI  - [Combination use of rh-bFGF and Bio-Oss collagen to enhance periodontal
      regeneration: an experimental study in dogs].
AB  - PURPOSE: To evaluate the effectiveness of combined use of rh-bFGF and Bio-Oss
      collagen compounds on regeneration of the canine periodontal tissues. METHODS:
      Four adult hybrid canine were selected and bone defect of 5mmx5mmx5mm in size was
      created in the mesio and distal alveolar crest where the premolars were lost in
      both sides of the maxilla and mandible. Three methods were used in 3 groups,in
      the experimental group 1, rh-bFGF and Bio-Oss collagen compounds were
      implanted,Bio-Gide were overlaid; in the experimental group 2,Bio-Oss collagen
      compounds were implanted, Bio-Gide were overlaid;in the control group only Bio
      Gide were overlaid. The therapeutic results were evaluated by clinical and
      imaging examination as well as histological index. SAS 6.2 software package was
      used for paired t test. RESULTS: 8 weeks post operation, there were various
      amounts of newly formed alveolar bone,cement and connective tissues in each 3
      wall intrabony defect. There was significant difference in alveolar osteogenesis
      between the control group(1.2mm+/-0.1mm) and the 2 experimental groups (3.7mm+/
      0.3mm, 2.3mm+/-0.2mm).The difference was also significant between the two
      experimental groups (P<0.01). There was no significant difference in newly formed
      cement and connective tissues among the 3 groups (P>0.05). CONCLUSIONS:
      Application of rh-bFGF/ Bio-Oss collagen compounds benefits to the regeneration
      of the alveolar bone and avoid the side effects of root resorption ,bone malunion
      which often occur after conventional periodontal regeneration therapy.Addition of
      rh-bFGF/ Bio-Oss collagen compounds was useless to cement genesis and periodontal
      ligament formation.

PMID- 17546393
TI  - [Effect of different nanophase hydroxyapatite particles on osteoblasts
      metabolism].
AB  - PURPOSE: To compare two different structural nanophase hydroxyapatite(HA)
      particles on the proliferation activity and functions of osteoblasts. METHODS:
      Primary culture of osteoblasts from rat calvaria was established and then
      cultured on the coatings of different size of nano particles (groupI 20
      40nm,group II 70-100nm), the HA coatings without nano-particles was used as
      control group. Proliferation activity, protein content and synthesis of alkaline
      phosphatase(ALP) by osteoblasts were examined by MTT assay, coomassic brilliant
      blue method and PNPP test, and statistical significance was assessed by multiple
      comparison (q test, SNK) in one-way analysis of variance (ANOVA) with SPSS10.0
      software package. RESULTS: Osteoblasts grew well on HA coatings. MTT assay
      demonstrated that there was significant difference between group I and group II
      at 6th day and 8th day (P<0.05).At first half stage(5th day and 10th day) ALP
      activity test showed no significant difference between group I and groupII
      (P>0.05) and as the culture going on(15th day and 20th day), there was
      significant difference between the two groups (P<0.05). Coomassic brilliant blue
      method showed that there was significant difference between group I and group II
      from 5th day to 20th day (P<0.05). CONCLUSION: The diameter of nano-particles on
      the HA coatings could influence the proliferation activity and functions of the
      osteoblasts. The nano-particles of similar size with HA crystal in vivo showed
      better cytocompatibility.

PMID- 17546394
TI  - [An experimental study of the effects of root-canal treatment on orthodontic
      movement in cat cuspids].
AB  - PURPOSE: To evaluate the effectiveness of orthodontic forces in moving teeth
      after root canal therapy and the risk of apical resorption which may happen
      during orthodontic movement in an animal model. METHODS: Under general
      anesthesia, root canal therapy was performed on the mandibular canines on one
      side of 16 adult cats. Tipping movement of the canines was induced with an
      orthodontic spring (100 to 120 g). Eight weeks later, tooth movement was assessed
      from pre- and posttreatment mandibular casts, including measurement of root
      lengths in both radiographs and histological sections. All the data were analysed
      with SPSS 11.0 for windows. Student's t test was used for comparisons between
      paired groups. RESULTS: The results showed that teeth after root canal therapy
      and vital teeth moved similar distances when subjected to the same forces
      (P>0.05). And teeth after root canal therapy had greater loss of cementum after
      tooth movement than vital teeth (P<0.05), but without significant differences in
      radiographic root length (P>0.05). CONCLUSIONS: Teeth after root canal therapy
      can be moved orthodontically as readily as vital teeth when subjected to the same
      orthodontic forces under the conditions of the study. However, teeth after root
      canal therapy have more root resorption than vital teeth during orthodontic
      movement which may not be detected form the radiography.

PMID- 17546395
TI  - [Gene therapy of bone morphogenetic protein-2 for periodontal tissue regeneration
      in vivo].
AB  - PURPOSE: To evaluate the effect of pIRES-rhBMP-2 gene on the regeneration of
      periodontal bone defects of beagle dogs in vivo. METHODS: Following surgery to
      create a U-shaped periodontal osseous defect on the buccal aspect of 6 mandibular
      premolar (P2,P3,P4) mesial roots, 6 adult beagle dogs were divided into three
      groups, pIRES-rhBMP-2 group, rhBMP-2 group and phosphate-buffered saline (PBS)
      group respectively. The animals were sacrificed after 4 or 8 weeks and the
      mandible taken for histological examination. Histometric measurements were
      performed with Image-Pro- Express system. The height of new bone and cementum and
      the formation of new connective tissue were analyzed and compared. The results
      were analyzed by N-K test using SAS6.12 software package. RESULTS: After 8 weeks,
      a complete osseous healing occurred and dense new periodontal ligament fibers
      rich in blood vessels were observed in the pIRES-rhBMP-2 group and the rhBMP-2
      group, whereas fewer new bone occurred and sparse collagen fibers aligned
      irregularly were observed in the blank control group. The height of new bone and
      cementum and the formation of new connective tissue were significantly greater in
      the two experimental group than in the blank control group (P<0.05,P<0.01),
      whereas there was no significant difference in the two experimental groups
      (P>0.05). CONCLUSION: pIRES-rhBMP-2 can accelerate the regeneration of dogs'
      periodontal bone defects.

PMID- 17546396
TI  - [Current gene study in etiological analysis of congenital craniofacial
      abnormalities].
AB  - The cause of congenital craniofacial abnormalities are very complicated.
      Understanding of the gene mechanisms of abnormalities taking place are very
      important for prevention and therapy.DNA sequence analysis provides the
      fundaments of gene study of the congenital craniofacial abnormalities. Human
      genome project (HGP) paved the confirmation of candidate gene of the congenital
      craniofacial abnormalities.Transgenic animal models and gene knockout techniques
      are effective methods in study of gene function. This paper reviews current gene
      study in etiopathogenisis analysis of the congenital craniofacial abnormalities.

PMID- 17546397
TI  - [Current application of confocal laser scanning microscope (CLSM) in
      stomatology].
AB  - Confocal laser scanning microscopy is one kind of modern Hi-tech on the basis of
      confocal imaging which is characterized by depth discrimination capability. It
      has been widely used in the field of stomatology due to its great advantages of
      non-destructive and non-invasive optical sectioning and three-dimensional
      reconstruction of the vital objects, in situ and dynamic real-time observation of
      the tissues and cells can be performed at high resolution. This paper reviews the
      fundamentals of confocal imaging and the application of CLSM in the fields of
      dental material, caries, dentin bonding interface and other basic researches in
      stomatology in recent years.

PMID- 17546398
TI  - Endovascular treatment of a bleeding secondary aorto-enteric fistula. A case
      report with 1-year follow-up.
AB  - We report a patient with life-threatening gastrointestinal bleeding caused by a
      secondary aorto-enteric fistula. Because the patient had several comorbid
      conditions, we succesfully stopped the bleeding by endovascular placement of a
      bifurcated aortic stent-graft. The patient developed periaortic infection 4
      months later, but he was managed with antibiotics. The patient is well 1 year
      after the procedure.

PMID- 17546399
TI  - Embolization with the Amplatzer Vascular Plug in TIPS patients.
AB  - Vessel embolization can be a valuable adjunct procedure in transjugular
      intrahepatic portosystemic shunt (TIPS). During the creation of a TIPS,
      embolization of portal vein collaterals supplying esophageal varices may lower
      the risk of secondary rebleeding. And after creation of a TIPS, closure of the
      TIPS itself may be indicated if the resulting hepatic encephalopathy severely
      impairs mental functioning. The Amplatzer Vascular Plug (AVP; AGA Medical, Golden
      Valley, MN) is well suited for embolization of large-diameter vessels and has
      been employed in a variety of vascular lesions including congenital arteriovenous
      shunts. Here we describe the use of the AVP in the context of TIPS to embolize
      portal vein collaterals (n = 8) or to occlude the TIPS (n = 2).

PMID- 17546400
TI  - Follow-up results of 71 patients undergoing metallic stent placement for the
      treatment of a malignant obstruction of the superior vena cava.
AB  - PURPOSE: To retrospectively clarify the utility of metallic stent placement for
      the treatment of the malignant obstruction of the superior vena cava (SVC) in 71
      patients with VC syndrome (SVCS) on the basis of long-term follow-up data.
      MATERIALS AND METHODS: Seventy-one patients underwent stent placement and were
      followed until death. The applicability of the spiral Z-stent (S-Z-stent) mainly
      used the initial and follow-up results, stent placement for bilateral BCV
      obstruction and the value of concurrent anticancer therapy were studied. RESULTS:
      The technical success rate was 100%, the initial clinical success rate was 87%
      (62/71), the primary clinical patency rate was 88% (57/65), and the secondary
      clinical patency rate was 95% (62/65). The obstruction rate of the stent was 12%
      (8/65), and an additional stent was useful for relief of recurrent SVCS. Survival
      of 57 patients in whom there was no recurrence of SVCS until death ranged from 1
      week to 29 months (mean, 5.4 months and the S-Z-stent appeared to be suitable for
      the treatment of the malignant obstruction of SVC. Unilateral stent placement was
      effective for relief of SVCS with bilateral BCV obstruction. Patients who
      received concurrent anticancer therapy survived 2 months longer than those who
      did not. CONCLUSION: Stent placement is an effective treatment for SVCS. Further,
      the utility of S-Z-stent for SVCS, an additional stent for recurrence, unilateral
      stent for patients with bilateral BCV obstruction, and anticancer therapy after
      stent placement were verified.

PMID- 17546401
TI  - Development of a hypertrophic ovarian artery after uterine artery embolization
      with polyvinyl alcohol particles.
AB  - Uterine artery embolization (UAE) for the treatment of symptomatic leiomyomata
      has shown excellent short-term clinical efficacy and minimal complications, yet
      recurrences after successful treatments at mid- and long-term follow-up have been
      reported. Exact etiologies for such recurrences have not been fully understood.
      We present a case of symptom recurrence with the development of a hypertrophic
      ovarian artery after successful UAE with polyvinyl alcohol particles,
      successfully treated with ovarian and repeat UAEs.

PMID- 17546402
TI  - Late intrahepatic hematoma complicating transjugular intrahepatic portosystemic
      shunt for Budd-Chiari syndrome.
AB  - Late intrahepatic hematoma is a rare complication of the transjugular
      intrahepatic portosystemic shunt (TIPS) procedure. We describe a patient with
      Budd-Chiari syndrome (BCS), who presented with a large inrahepatic hematoma 13
      days after TIPS. Review of the literature reveals only two previous cases, both
      occurring in patients with BCS and presenting after a similar time interval. This
      potentially serious complication appears to be specific for TIPS in BCS.

PMID- 17546403
TI  - The current role of venous sampling in the localization of endocrine disease.
AB  - Endocrine venous sampling plays a specific role in the diagnosis of endocrine
      disorders. In this article, we cover inferior petrosal sinus sampling, selective
      parathyroid venous sampling, hepatic venous sampling with arterial stimulation,
      adrenal venous sampling, and ovarian venous sampling. We review their indications
      and the scientific evidence justifying these indications in the diagnosis and
      management of Cushing's syndrome, hyperparathyroidism, pancreatic endocrine
      tumors, Conn's syndrome, primary hyperaldosteronism, pheochromocytomas, and
      androgen-secreting ovarian tumors. For each sampling technique, we compare its
      diagnostic accuracy with that of other imaging techniques and, where possible,
      look at how it impacts patient management. Finally, we incorporate venous
      sampling into diagnostic algorithms used at our institution.

PMID- 17546404
TI  - CT-guided biopsy of small liver lesions: visibility, artifacts, and corresponding
      diagnostic accuracy.
AB  - PURPOSE: Our study aimed to determine the visibility of small liver lesions
      during CT-guided biopsy and to assess the influence of lesion visibility on
      biopsy results. MATERIAL AND METHODS: Fifty patients underwent CT-guided core
      biopsy of small focal liver lesions (maximum diameter, 3 cm); 38 biopsies were
      performed using noncontrast CT, and the remaining 12 were contrast-enhanced.
      Visibility of all lesions was graded on a 4-point-scale (0 = not visible, 1 =
      poorly visible, 2 = sufficiently visible, 3 = excellently visible) before and
      during biopsy (with the needle placed adjacent to and within the target lesion).
      RESULTS: Forty-three biopsies (86%) yielded diagnostic results, and seven
      biopsies were false-negative. In noncontrast biopsies, the rate of insufficiently
      visualized lesions (grades 0-1) increased significantly during the procedure,
      from 10.5% to 44.7%, due to needle artifacts. This resulted in more (17.6%) false
      negative biopsy results compared to lesions with good visualization (4.8%),
      although this difference lacks statistical significance. Visualization impairment
      appeared more often with an intercostal or subcostal vs. an epigastric access and
      with a subcapsular vs. a central lesion location, respectively. With contrast
      enhanced biopsy the visibility of hepatic lesions was only temporarily improved,
      with a risk of complete obscuration in the late phase. CONCLUSION: In conclusion,
      visibility of small liver lesions diminished significantly during CT-guided
      biopsy due to needle artifacts, with a fourfold increased rate of insufficiently
      visualized lesions and of false-negative histological results. Contrast
      enhancement did not reveal better results.

PMID- 17546405
TI  - Failure of chronic transmyocardial laser revascularization to alter cardiac
      nociceptive reflexes: implications for the treatment of angina pectoris.
AB  - The aim of this study was to assess the delayed effects of transmyocardial laser
      revascularization (TMLR) on cardiac nociceptors. Experiments were performed in
      anesthetized dogs 1 month after thoracotomy with either TMLR (n = 17) or sham
      laser procedure (n = 17). All dogs underwent sinoaortic denervation and vagotomy
      to isolate the sympathetic afferent system. Left ventricular sympathetic
      afferents were stimulated by intracoronary bradykinin and transmural myocardial
      ischemia. Efferent responses were measured by direct recording of renal
      sympathetic nerve activity. Renal nerve responses to intracoronary bradykinin
      administered to the laser-treated anterior ventricular wall were not
      significantly different from those observed from the unlased posterior wall.
      Anterior transmural ischemia elicited similar renal nerve responses in laser
      treated and sham groups. Pathologic analysis showed intact neural structures in
      the subepicardial regions both near and remote from the lased channels. We
      conclude that reflexes mediated by left ventricular sympathetic afferents are
      preserved after chronic TMLR. These findings do not support the neural hypothesis
      for angina relief.

PMID- 17546406
TI  - Melt fracture of entangled polymers.
AB  - We construct a model for a slippage plane in a sheared melt, based on a balance
      between reptation bridging and shear debonding. The resulting state could show up
      at rather low shear rates and be locally stable. But it is not easy to nucleate:
      the conventional entangled state is also locally stable. We propose that slippage
      occurs on solid walls: either at the container surface, or on dust particles
      floating in the melt. Slippage at solid/melt interfaces was studied
      (experimentally and theoretically) long ago. There is a critical stress sigma*
      for slippage: our estimate (for strong adsorption of melt chains on the solid)
      gives sigma* approximately 1/3 (plateau modulus) for typical cases. Thus, melt
      fracture is expected at moderate stresses, in agreement with observations by S.Q.
      Wang and coworkers.

PMID- 17546407
TI  - Sulfide increases labile iron pool in RD4 cells.
AB  - A linkage between sulfur and iron metabolism has been suggested since sulfide has
      the ability to release iron from ferritin in the presence of iron acceptors in
      vitro. Nevertheless, this linkage is still lacking evidence in vivo as well as in
      cellular models. In this study we have treated human RD4 skeletal muscle cells
      with sodium sulfide and measured the level of the labile iron pool (LIP) as well
      as the intracellular sulfide concentration. We have also detected the amounts of
      L-ferritin protein as well as the iron regulatory protein 2 (IRP2). The sulfide
      treatment resulted in a 100% increase in the amount of LIP after 1 and 2 h. We
      also found that the raise of the LIP levels was coupled to an elevation of the
      amounts of intracellular sulfide that increased by 60%. The bioavailability of
      the released iron was confirmed by a 100% increase in L-ferritin protein as well
      as a 60% decrease of the IRP2 protein levels. These results suggest that there is
      a linkage between sulfur metabolism and intracellular iron regulation in
      mammalian cells.

PMID- 17546408
TI  - In vitro interactions between the oral absorption promoter, sodium caprate
      (C(10)) and S. typhimurium in rat intestinal ileal mucosae.
AB  - PURPOSE: The medium chain fatty acid, sodium caprate (C(10)), is a promising oral
      drug delivery agent that may promote permeability of peptides through increasing
      paracellular permeability of the intestinal epithelium. One safety concern is
      that it may permit co-absorption of by-stander agents including pathogens. The
      purpose of this in vitro study was to examine the effects of C(10) on rat
      intestinal ileal mucosae in the presence of co-administered Salmonella
      typhimurium in a low volume vertical Ussing chamber. METHODS: C(10) or S.
      typhimurium was added to rat ileal mucosae mounted in chambers and the flux of
      the paracellular flux of [(14)C]-mannitol examined. S. typhimurium adherence and
      uptake by ileal mucosae was also examined by counting. Bacterial growth curves
      were assessed in the presence of C(10). Minimum inhibitory- and bacteriocidal
      concentrations of C(10) were determined against a range of bacteria. RESULTS:
      Apical addition of either C(10) or S. typhimurium to rat ileal mucosae mounted in
      modified diffusion chambers significantly increased the flux of [(14)C]-mannitol
      in a concentration-dependent fashion. Co-exposure with increasing concentrations
      of C(10) attenuated the Salmonella-induced increase in mannitol flux.
      Histological evaluation revealed that C(10) inhibited both adhesion and invasion
      of S. typhimurium to intestinal mucosae. Short term bacterial growth studies in
      the presence of C(10) showed evidence of concentration-dependent inhibition.
      C(10) was bacteriocidal in mM concentrations against S. typhimurium and selected
      gram positive and negative bacteria. CONCLUSIONS: C(10) does not promote the
      permeation of a common bacterium across isolated intestinal tissue upon acute co
      exposure. It prevents S. typhimurium attachment to epithelia and impedes growth
      of a range of different bacterial strains.

PMID- 17546409
TI  - Binding of betaxolol, metoprolol and oligonucleotides to synthetic and bovine
      ocular melanin, and prediction of drug binding to melanin in human choroid
      retinal pigment epithelium.
AB  - PURPOSE: To characterize the binding of betaxolol, metoprolol and
      oligonucleotides to synthetic and bovine ocular melanin, and to predict the
      binding to melanin in human choroid-retinal pigment epithelium (RPE). MATERIALS
      AND METHODS: The shape, size and specific surface area of synthetic melanin and
      isolated melanin granules from bovine choroid-retinal pigment epithelium (RPE)
      were characterized by SEM, laser diffractometry and BET. The binding of
      betaxolol, metoprolol, fluorescein isothiocyanate (FITC)-labeled phosphodiesther
      oligonucleotides and 6-carboxyfluorescein (6-CF) to melanin was determined. The
      binding of beta-blockers to melanin in human choroid-RPE was estimated based on
      binding parameters and the melanin content in human choroid-RPE. RESULTS: Bovine
      melanin granules were round or oval with a mean diameter of ca. 1 mum. Synthetic
      granules were slightly smaller and irregular and had a two times higher specific
      surface area than bovine melanin. Synthetic melanin bound more betaxolol and
      metoprolol than bovine melanin and both melanin types showed a high affinity and
      a low affinity binding sites. The human choroid-RPE was predicted to contain 3-19
      times more melanin bound drug than unbound drug at typical therapeutic
      concentrations (1-1,000 ng/ml). FITC-labeled oligonucleotides and 6-CF did not
      bind to melanin. CONCLUSIONS: The binding of lipophilic drugs to biological
      melanin differs from that of synthetic melanin. Lipophilic beta-blockers are
      expected to bind significantly to melanin in human choroid-RPE: only a small
      fraction of the drug being in active free form. In contrast, phosphodiesther
      oligonucleotides do not seem to bind to melanin.

PMID- 17546410
TI  - A novel light-cured glass-ionomer system for improved dental restoratives.
AB  - A novel light-cured glass-ionomer cement (LCGIC) system based on the 4-arm star
      shape poly(acrylic acid) (AA) tethered with glycidyl methacrylate has been
      developed. The 4-arm poly(AA) polymer was synthesized using atom-transfer radical
      polymerization. The purified polymer was used to formulate with water and Fuji II
      LC filler to form LCGICs. Compressive strength (CS) was used as a screening tool
      for evaluation. The effects of grafting ratio, polymer/water (P/W) ratio, filler
      powder/polymer liquid (P/L) ratio and aging on strengths were investigated. All
      the specimens were conditioned in distilled water at 37 degrees C for 24 h prior
      to testing. The results show that the 4-arm poly(AA) polymer exhibited a lower
      viscosity as compared to its linear counterpart that was synthesized via
      conventional free-radical polymerization. This novel LCGIC system was 13% in CS,
      86% in diametral tensile strength (DTS) and 123% in flexural strength higher but
      93.6% in shrinkage lower than Fuji II LC. Increasing P/W ratio significantly
      increased both CS and DTS. Upon increasing grafting ratio, the CS was increased
      from 35% to 50% but not from 50% to 70%. Likewise, when P/L ratio was increased,
      the CS was increased from 2.2 to 2.7 but not from 2.7 to 3.0. During aging, the
      ultimate CS (MPa) was significantly increased from 209.2 at 1 h to 329.7 at 1
      week. It appears that this novel LCGIC system will be a better dental restorative
      because it demonstrated improved mechanical strengths as well as little shrinkage
      and may eliminate cytotoxicity in current LCGICs caused by leached HEMA.

PMID- 17546411
TI  - Proliferation of osteoblasts and fibroblasts on model surfaces of varying
      roughness and surface chemistry.
AB  - Physical and chemical properties of the surfaces of implants are of considerable
      interest for dental and orthopedic applications. We used self-assembled
      monolayers (SAMs) terminated by various functional chemical groups to study the
      effect of surface chemistry on cell behavior. Cell morphology and proliferation
      on silicon wafers of various roughnesses and topographies created by chemical
      etching in caustic solution and by corundum sandblasting were analyzed as well.
      Water contact angle data indicated that oxidized wafer surfaces displayed high
      hydrophilicity, modification with poly(ethylene glycol) (PEG) created a
      hydrophilic surface, and an amino group (NH2) led to a moderately wettable
      surface. A hydrophobic surface was formed by hydrocarbon chains terminated by
      CH3, but this hydrophobicity was even further increased by a fluorocarbon (CF3)
      group. Cell proliferation on these surfaces was different depending primarily on
      the chemistry of the terminating groups rather than on wettability. Cell
      proliferation on CH3 was as high as on NH2 and hydrophilic oxidized surfaces, but
      significantly lower on CF3. Precoating of silicon wafers with cell culture serum
      had no significant influence on cell proliferation. Scanning electron microscopy
      indicated a very weak initial cell-surface contact on CF3. The cell number of
      osteoblasts was significantly lower on sandblasted surfaces compared with other
      rough surfaces but no differences were detected with 3T3 mouse fibroblasts. The
      different surface roughnesses and topographies were recognized by MG-63
      osteoblasts. The cells spread well on smooth surfaces but appeared smaller on a
      rough and unique pyramid-shaped surface and on a rough sandblasted surface.

PMID- 17546412
TI  - Effects of sterilization on an extracellular matrix scaffold: part I. Composition
      and matrix architecture.
AB  - The impact of peracetic acid (PAA), lyophilization, and ethylene oxide (EO)
      sterilization on the composition and three dimensional matrix structure of small
      intestinal submucosa (SIS), a biologic scaffold used to stimulate the repair of
      damaged tissues and organs, was examined. Fibronectin and glycosaminoglycans are
      retained in SIS following oxidation by peracetic acid and alkylation using
      ethylene oxide gas. Significant amounts of FGF-2 are also retained, but VEGF is
      susceptible to the effects of PAA and is dramatically reduced following
      processing. Further, matrix oxidation, lyophilization, and sterilization with EO
      can be performed without irreversibly collapsing the three dimensional structure
      of the native SIS. These structural features and growth promoting extracellular
      matrix constituents are likely to be important variables underlying cellular
      attachment, infiltration and eventual incorporation of SIS into healing host
      tissues.

PMID- 17546413
TI  - Effects of sterilization on an extracellular matrix scaffold: part II.
      Bioactivity and matrix interaction.
AB  - Small intestinal submucosa (SIS) has been successfully used to treat a variety of
      damaged or diseased tissues in human patients. As a biologic scaffold, SIS
      stimulates repair of damaged or diseased tissues and organs with tissue that is
      similar in structure and function to the material it was meant to replace. To
      meet clinical safety requirements, biologic materials from animal tissues must
      undergo processing treatments to minimize host immune response and to eliminate
      the possibility of disease transmission. The effect of peracetic acid
      disinfection, lyophilization, and ethylene oxide sterilization on the in vitro
      bioactivity of the processed SIS was therefore examined in murine fibroblasts and
      pheochromocytoma (PC12) cells. Specifically, the ability of processed SIS to
      support fibroblast attachment, to stimulate PC12 cell differentiation, and to
      upregulate fibroblast VEGF secretion was examined. Fibroblasts attach to the
      sterilized SIS, remain viable, and more than double their secretion of VEGF as a
      result of interacting with the SIS matrix components. Additionally, PC12 cells
      exhibit increased neurite outgrowth following stimulation by SIS matrix proteins
      versus controls. We conclude that a biologic scaffold can be prepared for human
      use and still retain significant bioactivity.

PMID- 17546414
TI  - Growth of human osteoblast-like cells on beta-tricalciumphosphate (TCP) membranes
      with different structures.
AB  - Bioresorb, a bioactive, bioresorbable bone replacement material, consisting of
      pure beta-tricalciumphos phate (TCP) ceramic, was evaluated in cell culture with
      human osteoblast-like cells. The aim of our study was to investigate the
      influence of TCP on the growth behavior of human osteoblast-like cells. Different
      granule sizes and plate sizes were used in this study: Granule sizes 500-1000
      microm, 1000-2000 microm and 2000-5000 microm; plate sizes 1.7 mm, 2.0 mm and 2.2
      mm. Under scanning electron microscopic (SEM) observations the cell colonization
      on the surface of the biomaterial and the tissue compatibility were studied. Thin
      sections were used to study the growth of human osteoblast-like cells inside the
      biomaterial. It could be clearly shown that all investigated biomaterials are
      tissue compatible and that the size and structure (granule or plate) of the
      biomaterial effects the colonization rate. Bioresorb plates enhance the
      colonization comparable to granule. The results obtained by SEM and thin sections
      were confirmed immunhistochemically by the nonradioactive assay EZ4U - EASY FOR
      YOU.In conclusion, all investigated sizes and structures of Bioresorb are tissue
      compatible but the cell growth is much better on plates than on granule small in
      size. The results suggest that the plates may be favourable useful as scaffold
      for regrowth of bone.

PMID- 17546415
TI  - Surface characteristics and bioactivity of oxide film on titanium metal formed by
      thermal oxidation.
AB  - In this study, we characterized the surface of oxide film formed on titanium
      metal through the use of thermal treatment and investigated the effect of surface
      characteristics on the bioactivity of titanium. The as-received sample group was
      prepared by polishing and cleaning CP-Ti as a control group, and thermally
      oxidized sample groups were prepared by heat treating at 530, 600, 700, 800, 900,
      and 1000 degrees C respectively. Micro-morphology, crystalline structure,
      chemical composition, and binding state were evaluated using FE-SEM, XRD, and
      XPS. The bioactivity of sample groups was investigated by observing the degree of
      calcium phosphate formation from immersion testing in MEM. The surface
      characterization tests showed that hydroxyl group content in titanium oxide film
      was increased, as the density of titanium atoms was high and the surface area was
      large. In MEM immersion test, initial calcium phosphate formation was dependent
      upon the thickness of titanium oxide, and resultant calcium phosphate formation
      depended on the content of the hydroxyl group of the titanium oxide film surface.

PMID- 17546416
TI  - Two different types of age-hardening behaviors in commercial dental gold alloys.
AB  - Age-hardening behavior during continuous heating in commercial dental casting
      gold alloys was investigated by means of electrical resistivity measurements,
      hardness tests and X-ray diffraction. Two distinguishable behaviors were
      detected. It is considered that the difference was attributed to the amount of
      platinum, and the atomic ratio of gold and copper in each alloy. The phase
      transformations during continuous heating progressed into two steps (stages I and
      II). Increase of the platinum addition in gold-based alloys retards the rate of
      the reaction and decreases remarkably the amount of stage I.

PMID- 17546417
TI  - Preoperative opacification of acrylic intraocular lenses in storage.
AB  - The preoperative opacification of acrylic intraocular lenses (IOLs) was
      investigated in order to determine its cause. Opacified IOLs were examined by
      energy dispersive X-ray (EDX), the buffer solutions were analysed by inductively
      coupled plasma optical emission spectroscopy (ICP-OES) and the rubber seals used
      in the bottles in which the IOLs were stored were ashed and tested. The deposit
      covering the opacified lenses contained a significant amount of zinc, which was
      absent from fresh IOLs and buffer solution. The source of this was found to be
      the rubber seals used to seal the glass bottles in which the IOLs were stored.
      There were two types of rubber seals used, red and grey in colour. The buffer
      solutions in which opacification had occurred was also contaminated with zinc,
      but this was only noticeable when using the red seals. This contamination was
      reproduced by boiling red seals in fresh buffer solution for eighty minutes, to
      simulate autoclaving. It was concluded that zinc from the zinc oxide used as
      filler in the rubber seals was leaching into the buffer solution and causing the
      IOLs to become opacified. This was found to be much worse in the case of the red
      seals than for the grey ones. However, minute crystals were found on the IOLs
      stored using the grey ones, which could potentially act as nucleation points for
      postoperative opacification.

PMID- 17546418
TI  - Microindentation in bone: hardness variation with five independent variables.
AB  - Microindentation is an investigational tool often used to determine hardness and
      other derived material properties of the material bone. This study explored the
      variation of microindentation hardness results with five independent variables.
      The variables were: applied mass, dwell time, drying time, time between
      indentation and measurement, and distance between the center of an indentation
      and the edge of other indentations and pores. These variables were selected
      because they represented a reasonable range of specimen investigational steps. We
      also investigated the cross sections of typical indentation residual impressions
      to determine the degree of material pile-up at the edges of the impressions. We
      found that microindentation hardness varied with applied mass and with distance
      between the indentation and neighboring indentations and pores but not with the
      other variables. Our recommended minimum applied mass is 0.10 kg versus a
      previously published value of 0.05 kg. We also found no discernable material pile
      up at the residual impression edges, in contrast to reports of others.

PMID- 17546419
TI  - Evaluation of the influence of albumin on the mineralization of a glass by Atomic
      Force Microscopy.
AB  - Bioactive glasses have been used as a graft material that can stimulate the
      formation of a new bone. In vitro tests usually give sensible indications about
      the potential bioactivity of these glasses. In the present work the influence of
      egg albumin on the formation of a Ca-P precipitate on a glass of the system
      SiO(2)-CaO-MgO-P(2)O(5) was evaluated. The samples were immersed in simulated
      body fluid (SBF) that simulates the composition of human plasma, with and without
      albumin. After immersion in this solution for 7 and 14 days, the glass was
      characterized by X-Ray Diffraction (XRD) and Atomic Force Microscopy (AFM). AFM
      results of the samples after immersion in SBF with albumin show the development
      of a precipiate formed from the solution/substrate reaction. Glasses immersed in
      albumin-free SBF exhibit the formation of a thin layer easily detached from the
      substrate. XRD results indicate that the precipitate is essentially amorphous,
      evolving to octacalcium phosphate. As the formation of an adherent precipitate on
      the glass samples only occurred when the substrate was immersed in SBF with
      albumin, it is suggested that albumin improves the mineralization on the glasses.

PMID- 17546420
TI  - Evaluation of different bonded investments for dental titanium casting.
AB  - The properties of several different investments were investigated including
      phosphate bonded, magnesia bonded, and alumina cement investments. Measurements
      included the setting expansion, thermal expansion, and compressive strength of
      investments, as well as the tensile strength, elongation, Vickers hardness (VHN)
      and surface roughness of titanium castings. For phosphate bonded investment, the
      setting expansion after being mixed with its own mixing solution was 2.10%, which
      was larger than the other investments; the thermal expansion was -0.25% at 200
      degrees C, the compressive strength 14 and 5 MPa after heating. For titanium cast
      in phosphate bonded investment, the hardness on its top surface was 655 Hv, the
      tensile strength was 379 MPa, the elongation was 19.4%, and the surface roughness
      was 2.29 microm. Athough the thermal expansion of phosphate bonded investment is
      small, the setting expansion is large enough to compensate for the shrinkage of
      titanium castings. As its thermal expansion at T >/= 600 degrees C was constant
      and its heating-cooling cycle was almost reversible, these two properties can
      reduce the thermal shock and thus avoid cracking of the investment.

PMID- 17546421
TI  - Cell behaviour on phospholipids-coated surfaces.
AB  - Effective integration of orthopedic biomaterials requires the rapid formation of
      the inorganic mineral phase during the first hours of implantation and the
      subsequent adhesion and proliferation of the osteoblasts. It has recently been
      demonstrated that phosphatidylserine-rich phospholipid coatings can induce a fast
      mineralisation of titanium implant surfaces on incubation in simulated body
      fluids. The aim of this work was to investigate the biocompatibility of these
      coatings in terms of cytotoxicity and ability to support osteoblast adhesion and
      activity. Cytotoxicity and cell adhesion to uncoated titanium, calcified
      phospholipid-coated titanium and HA-coated titanium was assessed using
      fibroblasts and osteoblast-like cells. The synthesis of type I collagen by
      osteoblast-like cells cultured on the calcified-phospholipid coatings was also
      comparable to that observed for osteoblast-like cells cultured on the titanium
      and HA-Ti surfaces.The results suggest that the fast mineralization of the
      phospholipid matrix, obtained in vitro by its pre-treatment in a SBF, exposes the
      cells to an environment similar to that present in the bone during its natural
      formation that allow cells to adhere, proliferate and produce proteins
      fundamental for bone growth. The biocompatibility of these phospholipid-based
      coatings, in combination with their ability to initiate rapid mineralisation,
      provides a promising material that could in vivo create bone cell interactions
      and bone integration.

PMID- 17546422
TI  - Hydroxyapatite forming ability of electrostatic spray pyrolysis derived calcium
      phosphate nano powder.
AB  - A novel fabrication technique, i.e., electrostatic spray pyrolysis (ESP), has
      been used in this study to prepare calcium phosphate nano powders. Final
      annealing was done at 400 degrees C for 30 min in air. The hydroxyapatite-forming
      ability of the annealed powder has been investigated in Eagle's minimum essential
      medium solution. X-ray diffracton, field emission scanning electron microscope,
      energy dispersive X-ray spectroscope, and Fourier transform infrared spectroscope
      were employed to characterize the annealed powders after immersion. The powder
      with an amorphous structure induced hydroxyapatite formation on their surfaces
      after immersion for 15 days.

PMID- 17546423
TI  - Examination of local variations in viscous, elastic, and plastic indentation
      responses in healing bone.
AB  - A viscous-elastic-plastic indentation model was used to assess the local
      variability of properties in healing porcine bone. Constant loading- and
      unloading-rate depth-sensing indentation tests were performed and properties were
      computed from nonlinear curve-fits of the unloading displacement-time data. Three
      properties were obtained from the fit: modulus (the coefficient of an elastic
      reversible process), hardness (the coefficient of a nonreversible, time
      independent process) and viscosity (the coefficient of a nonreversible, time
      dependent process). The region adjacent to the dental implant interface
      demonstrated a slightly depressed elastic modulus along with an increase in local
      time-dependence (smaller viscosity); there was no clear trend in bone hardness
      with respect to the implant interface. Values of the elastic modulus and
      calculated contact hardness were comparable to those obtained in studies
      utilizing traditional elastic-plastic analysis techniques. The current approach
      to indentation data analysis shows promise for materials with time-dependent
      indentation responses.

PMID- 17546424
TI  - A micromechanical elastic property study of trabecular bone in the human
      mandible.
AB  - Micromechanical properties of human mandibular trabecular bone, with particular
      interest to any site differences were investigated. A mandible was harvested from
      a 66 year-old female cadaver free from bone disease. It was embedded in PMMA, cut
      into 2mm sections and polished. Micromechanical property measurements were
      obtained using the UH3 Scanning Acoustic Microscope (SAM) (Olympus Co., Tokyo,
      Japan) at 400MHz in the burst mode. 6 vertical slices from the right and 6
      horizontal slices from the left were chosen. In each of the 12 samples, 3 points
      were measured; first in the center, the other 2 from the margins. Data were
      analyzed statistically by SPSS (SPSS, Inc.) using Student's t-test. The average
      value of reflection coefficient r is 0.58+/-0.079 with the range from 0.46 to
      0.64; E=25.0+/-5.64 GPa. There is no significant difference in properties in the
      osteonal direction of related cortical bone and those found between the marginal
      area and center areas. The average value of r from the right side, 0.60+/-0.07,
      is statistically higher than the average value of from the left side, 0.56+/
      0.07. Micromechanical properties of both mandibular trabecular and cortical bone
      have almost the same values.

PMID- 17546425
TI  - Preparation and in vivo investigation of artificial cornea made of nano
      hydroxyapatite/poly (vinyl alcohol) hydrogel composite.
AB  - An artificial cornea consisted of a porous nano-hydroxyapatite/poly (vinyl
      alcohol) hydrogel (n-HA/PVA-H) skirt and a transparent center poly (vinyl
      alcohol) hydrogel (PVA-H) were prepared. The n-HA/PVA-H skirt was homogeneously
      porous and these pores were interconnected. Inter-penetrating network was
      observed along the interface between the core and the skirt. Artificial corneas
      were implanted in eyes of rabbit. The corneal tissues were evaluated
      histological. The results displayed that a good biocompatibility and interlocking
      had happened between artificial cornea and host tissues. This novel cornea
      prepared here is potential to be used clinically.

PMID- 17546426
TI  - Studies on the use of hollow fibre membrane bioreactors for tissue generation by
      using rat bone marrow fibroblastic cells and a composite scaffold.
AB  - Production of sufficient tissue in vitro for use in tissue engineering is limited
      mainly by the absence of adequate oxygenation and appropriate transport of
      nutrients to, and waste product from, the tissue. To overcome the limitations of
      diffusive transport, the possibility of growing three dimensional (3D) tissue
      structures by using hollow fibre membrane bioreactors (HFMB) has been considered
      in this study. The hollow fibre membranes, embedded in the 3D scaffold, are
      porous and semi-permeable and can thus serve similar functions to arteries and
      veins in vivo. Collagen gel and Cytodex 1 microcarriers were used as a composite
      3D scaffold and permeating cellulose acetate hollow fibre membranes were attached
      to both ends of a polycarbonate cylindrical shell to form a bioreactor. Rat bone
      marrow fibroblastic (RBMF) cells were seeded initially onto Cytodex 1
      microcarriers and these were subsequently mixed with collagen gel before
      inoculation into the bioreactor. Bioreactors were perfused by culture medium
      through the hollow fibre membranes for a one week period. Bioreactors containing
      cells cultured under similar conditions except for the lack of perfusion of
      medium served as controls. The proliferation, viability, metabolism and
      morphological appearances of the cells in the perfused and non-perfused
      constructs were compared. The results indicated that there was significantly
      greater maintenance of functional activity and normal cellular morphology in the
      perfused group than in the non-perfused group. Further studies are required to
      evaluate the additional advantages of using this novel HFMB for growing 3D dense
      tissues.

PMID- 17546427
TI  - Ion release by endodontic grade glass-ionomer cement.
AB  - Cylindrical specimens (6 mm high x 4 mm diameter) of the endodontic grade glass
      ionomer (Ketac Endo) were exposed to various media for 1 week, after which
      changes in their mass, pH of storage medium, and ion release were determined. In
      water, this cement was shown to release reasonable amounts of sodium, aluminium
      and silicon, together with smaller amounts of calcium and phosphorus, as well as
      taking up 2.41% by mass of water. A comparison with the restorative grade
      materials (Ketac Molar, ex 3M ESPE and Fuji IX, ex GC) showed both ion release
      and water uptake to be greater. All three cements shifted pH from 7 to around 6
      with no significant differences between them. Other storage media were found to
      alter the pattern of ion release. Lactic acid caused an increase, whereas both
      saturated calcium hydroxide and 0.6% sodium hypochlorite, caused decreases. This
      suppression of ion-release may be significant clinically. Aluminium is the most
      potentially hazardous of the ions involved but amounts released were low compared
      with levels previously reported to show biological damage.

PMID- 17546428
TI  - Chemical-physical and preliminary biological properties of poly (2
      hydroxyethylmethacrylate)/poly-(epsilon-caprolactone)/hydroxyapa- tite composite.
AB  - In the present study, the synthesis of a semi-Interpenetrating Polymer Network
      (semi-IPN) incorporating linear poly-(epsilon-caprolactone) (PCL) into cross
      linked poly-(2-hydroxyethylmethacrilate) (PHEMA) reinforced with hydroxyapatite
      (HA) has been described. The aim of this study was to improve the mechanical and
      biological performance of the PHEMA/PCL in the hydrated state, for orthopaedic
      applications. The swelling behaviour, mechanical (compressive and tensile) and
      surface chemical-physical (morphology, stoichiometric composition)
      characterisation of the novel HA reinforced composite based on PHEMA/PCL polymer
      matrix, PHEMA/PCL 70/30 (w/w) + 50% (w/w) HA (PHEMA/PCL/HA), were evaluated.
      Furthermore, a preliminary in vitro biological evaluation was also performed on
      the composite using a fully characterised primary human osteoblast-like (HOB)
      cell model. The inclusion of HA in the composite improved the mechanical
      performance in the swollen state, with values of elastic modulus in a similar
      range to that of trabecular bone. The composite surfaces showed a porous,
      irregular topography with the presence of: oxygen (O), carbon (C); phosphorous
      (P); calcium (Ca) where the Ca/P ratio was 1.78. Biological evaluation indicated
      undetectable weight loss of the sample, no release of toxic leachables from the
      composite and pH values within an acceptable range for cell growth. The results
      indicate that the novel PHEMA/PCL/HA composite is a promising candidate as filler
      or substitute for spongy bone for orthopaedic applications.

PMID- 17546429
TI  - Mechanical properties and apatite forming ability of TiO2 nanoparticles/high
      density polyethylene composite: Effect of filler content.
AB  - Composite materials consisting of TiO(2) nanoparticles and high-density
      polyethylene (HDPE), designated hereafter as TiO(2)/HDPE, were prepared by a
      kneading and forming process. The effect of TiO(2) content on the mechanical
      properties and apatite forming ability of these materials was studied. Increased
      TiO(2) content resulted in an increase in bending strength, yield strength,
      Young's modulus and compressive strength (bending strength = 68 MPa, yield
      strength = 54 MPa, Young's modulus = 7 GPa, and compressive strength = 82 MPa) at
      50 vol% TiO(2). The composite with 50 vol% TiO(2) shows a similar strength and
      Young's modulus to human cortical bone. The TiO(2)/HDPE composites with different
      TiO(2) contents were soaked at 36.5 degrees C for up to 14 days in a simulated
      body fluid (SBF) whose ion concentrations were nearly equal to those of human
      blood plasma. The apatite forming ability, which is indicative of bioactivity,
      increased with TiO(2) content. Little apatite formation was observed for the
      TiO(2)/HDPE composite with 20 vol% content. However, in the case of 40 vol%
      TiO(2) content and higher, the apatite layers were formed on the surface of the
      composites within 7 days. The most potent TiO(2) content for a bone-repairing
      material was 50 vol%, judging from the mechanical and biological results. This
      kind of bioactive material with similar mechanical properties to human cortical
      bone is expected to be useful as a load bearing bone substitute in areas such as
      the vertebra and cranium.

PMID- 17546430
TI  - Bulgarian Bone Marrow Donors Registry--past and future directions.
AB  - Recently Bulgarian Bone Marrow Donors Registry (BBMDR) has been established and
      since August 2005 it has been a member of Bone Marrow Donors Worldwide. Currently
      the number of healthy donors included in the BBMDR is relatively low. All donors
      included in the BBMDR are typed for HLA-A, -B, -DRB loci. Phylogenetic analysis
      based on HLA allele frequencies shows that Bulgarians were characterized with
      closest genetic similarity to Macedonians, Greeks, Romanians, Cretans and
      Sardinians in comparison to the other European and Mediterranean populations. On
      the contrary the second largest ethnic minority-the Roma were the closest to the
      other Roma populations and North Indians. These differences were due to the
      predominance of alleles and haplotypes that are specific for the Asian and the
      other Roma populations. These specific genetic profiles in the Bulgarian ethnic
      minorities justify the need of an adequate representation of minorities in BBMDR.
      Future directions for BBMDR development are discussed, including an increase of
      the total number of donors and these for ethnic minorities, as well the
      enhancement of the level of resolution of the HLA typing for the donors in the
      registry.

PMID- 17546431
TI  - Cord blood stem cell transplantation. Why it is necessary to establish a
      Bulgarian cord blood bank?
AB  - The allogenic transplantation of hemopoietic stem cell from bone marrow and
      peripheral blood is limited due to the necessity to identify HLA matched donor
      within the family or in bone marrow donor registries. Although, more than 10
      million donors are available worldwide, completely HLA matched donors could be
      found only for 75% of the patients. It is well known that transplantations of
      hematopoietic stem cell from cord blood are characterized with a lower risk of
      GvHD and therefore do not require so strict criteria for HLA matching, and less
      time for search of matched donor is needed. The necessity to establish a National
      cord blood bank in Bulgaria is emphasized further by the heterogeneity of HLA
      allele and haplotype distribution in the Bulgarian population. That could be
      explained by the ethnic diversity of the population. As a result some alleles are
      more frequent in Bulgarians compared to other populations. The organization,
      accreditation, and development of a strategy for a National cord blood bank will
      be discussed.

PMID- 17546432
TI  - [Photodynamic therapy: non-oncologic indications].
AB  - While efficacy of topical photodynamic therapy (PDT) for the treatment of
      superficial non-melanoma skin cancer is already well-proven by several controlled
      clinical trials, there are only a few controlled studies showing efficacy of PDT
      for non-oncologic skin disorders. This report provides information on the use of
      PDT for inflammatory skin disorders, disorders of the pilosebaceous unit,
      infections of the skin, sclerotic skin diseases and cosmetic indications.

PMID- 17546433
TI  - [Traumatic posterior shoulder dislocation : diagnosis and therapy].
AB  - In contrast to anterior dislocations, traumatic dorsal shoulder dislocation is a
      rare complication of upper extremity injuries. If the diagnosis is overseen and
      treated incorrectly, severe mobility restrictions might be the consequence for
      the injured individual. Hence, the aim of this article is to demonstrate the
      adequate diagnostic and therapeutic management and to critically discuss the
      literature.

PMID- 17546434
TI  - [Reduction of glenoid rim fractures after primary shoulder dislocation in
      external rotation].
AB  - The treatment of anterior glenoid rim fractures depends on the size of the
      fracture and the articular surface involved. The operative treatment is open or
      arthroscopic refixation. In cases with small fragments and a stable shoulder
      nonoperative treatment is recommended. In patients with a primary shoulder
      dislocation immobilization in external rotation has been showed to improve the
      position of the displaced labrum on the glenoid rim. However, whether external
      rotation can reduce displaced glenoid rim fractures is not known. With the use of
      CT the repositioning of a glenoid rim fracture in a single patient in external
      rotation is evaluated.A 26-year-old patient with an anterior glenoid rim fracture
      after a primary shoulder dislocation was referred to our shoulder service. After
      initial reduction a CT scan in internal and external rotation of the involved
      shoulder was performed. In the external rotation CT the glenoid rim fracture was
      reduced in anatomic position. The patient was immobilized in a 30 degrees
      external rotation brace for 4 weeks. Six weeks after trauma the internal rotation
      CT showed the fracture healed in the anatomic position. At the 1-year follow-up
      the Constant Score and the Rowe Score were 100 points each. In patients with
      anterior glenoid rim fractures immobilization of the shoulder in external
      rotation seems to allow a reduction of the fracture. A study with a large number
      of patients is under way to evaluate long-term results.

PMID- 17546435
TI  - [Navigation for placement of scaphoid screws : a new indication for
      intraoperative 3D navigation-a cadaver study].
AB  - INTRODUCTION: Up to now, the use of navigation systems for the placement of
      scaphoid screws has been impossible, mainly because there have been no ways of
      fixing the reference markers. Faulty placement rates in internal fixation of the
      scaphoid show there is a current need for a 3D image-based navigation system and
      intraoperative monitoring of how successful the procedure will be. For this
      reason, we have developed a new radiotransparent hand fixation device (Scaph
      Splint), which allows reliable and accurate drilling of the scaphoid using 3D
      navigation. Tests of this device and the simultaneous precise placement of screws
      securing an internal fixation device are described in this paper. MATERIAL AND
      METHODS: Relative movements between the wrist and fixation device were measured
      with a 3-D ultrasound motion analyser system. Five cadaveric upper extremity
      specimens were then used for further navigated test applications. Each specimen
      was placed in the fixation device, and both the forearm and hand were secured to
      the two surfaces, with the wrist in approximately 80 degrees of extension. A
      reference marker was then securely fixed to the fixation device. A commercial
      navigation system and 3-D fluoroscopic imaging were used for each trial. Under
      navigation, the scaphoid was drilled in retrograde fashion, and a screw was
      placed into the drilled hole. Following screw placement, a 3D scan was performed
      to evaluate its position. The screw placement was analysed blindly to optimal
      placement and drill or screw perforation, and the image quality was rated on a
      visual analog scale (VAS). RESULTS: There were few artefacts, and the image
      quality of the 3-D scan was judged as as good (VAS 79). Deviations of >or=0.2 mm
      between planned trajectory and drilling tunnal were not found in any of the
      specimens; there were deviations of >or=1 mm in one case, and all other cases
      showed deviations of <or=1 mm. There were no registration failures of the
      navigation system, indicating that no loosening of the reference marker or
      movement of the hand occurred. There was one case of scaphoid perforation at the
      distal pole. DISCUSSION: We found that the Scaph-Split allowed complete
      immobilisation of the hand and carpus. This allowed for adequate reference
      tracker stability and subsequent successful 3D navigated fluoroscopic drilling
      and screw placement in the scaphoid. While further tests on fresh-frozen cadavers
      is warranted, this technique may prove clinically to be very useful for surgeons
      treating scaphoid fractures.

PMID- 17546436
TI  - [Vacuum-assisted closure therapy. Current status and basic research].
AB  - The gap between the broad clinical use of vacuum-assisted closure therapy (VT)
      and knowledge of the physiological mechanisms leading to its effectiveness is
      great. The value of the technique and its future development are dependent on
      research into these mechanisms. A meta-analysis evaluating the results of basic
      research on the effectiveness of VT was carried out based on peer reviewed
      publications. This is considered in relation to other therapeutic approaches of
      basic research to wound healing (growth factors etc.). Our study includes a
      concise description of the scientific background to the mechanisms of cell
      stimulation using basic work on tissue expansion, bone, vessel and nerve
      distraction as well as in vitro cell stimulation. Evaluation of the scientific
      data on all known effects of VT was made based on the results from experimental
      animal studies, the results of randomized clinical studies, observations on
      clinical applications and case reports. Assessment of the studies was based on
      design and significance as well as the appraisal of our own clinical experience.
      Data involving cellular effects (proliferation, synthesis, wound healing),
      systemic effects (mediators, systemic inflammatory disease), extracellular
      effects (perfusion, edema, local wound environment, stabilization, barriers) and
      complex effects of VT (inflammation, matrix function, blood supply) were
      examined. Systematic analysis of the data allows scientifically interested
      surgeons rapid access to the theme, the first, to this extent, extensive overview
      of the current scientific situation as well as a comprehensive bibliography for
      all areas involving the theme of mechanical cell stimulation. The authors list
      major areas for future research and encourage the development of multicenter
      studies.

PMID- 17546437
TI  - Wasps robbing food from ants: a frequent behavior?
AB  - Food robbing, or cleptobiosis, has been well documented throughout the animal
      kingdom. For insects, intrafamilial food robbing is known among ants, but social
      wasps (Vespidae; Polistinae) taking food from ants has, to the best of our
      knowledge, never been reported. In this paper, we present two cases involving
      social wasps robbing food from ants associated with myrmecophytes. (1)
      Polybioides tabida F. (Ropalidiini) rob pieces of prey from Tetraponera aethiops
      Smith (Formicidae; Pseudomyrmecinae) specifically associated with Barteria
      fistulosa Mast. (Passifloraceae). (2) Charterginus spp. (Epiponini) rob food
      bodies from myrmecophytic Cecropia (Cecropiaceae) exploited by their Azteca
      mutualists (Formicidae; Dolichoderinae) or by opportunistic ants (that also
      attack cleptobiotic wasps). We note here that wasps gather food bodies (1) when
      ants are not yet active; (2) when ants are active, but avoiding any contact with
      them by flying off when attacked; and (3) through the coordinated efforts of two
      to five wasps, wherein one of them prevents the ants from leaving their nest,
      while the other wasps freely gather the food bodies. We suggest that these
      interactions are more common than previously thought.

PMID- 17546438
TI  - Cognitive performance in type 1 diabetes patients is associated with cerebral
      white matter volume.
AB  - AIMS/HYPOTHESIS: Cognitive performance in type 1 diabetes may be compromised as a
      result of chronic hyperglycaemia. The aim of this study was to investigate the
      cognitive functioning of patients with type 1 diabetes (including a subgroup with
      a microvascular complication) and nondiabetic controls, and to assess the
      relationship between cognition and cerebral grey and white matter volumes.
      MATERIALS AND METHODS: Twenty-five patients with type 1 diabetes (of whom ten had
      proliferative retinopathy) and nine nondiabetic controls (matched in terms of
      sex, age and education) underwent a neuropsychological examination and magnetic
      resonance imaging of the brain. Fractional brain tissue volumes (tissue volume
      relative to total intracranial volume) were obtained from each participant.
      RESULTS: Compared with nondiabetic controls, patients with diabetes performed
      worse on tests measuring speed of information processing and visuoconstruction;
      patients with microvascular disease performed worse on the former cognitive
      domain (p = 0.03), whereas patients without complications performed worse on the
      latter domain (p = 0.01). Patients with a microvascular complication had a
      significantly smaller white matter volume than nondiabetic controls (p = 0.04),
      and smaller white matter volume was associated with worse performance on the
      domains of speed of information processing and attention and executive function.
      CONCLUSIONS/INTERPRETATION: Patients with diabetes demonstrated several subtle
      neuropsychological deficits, which were found to be related to white matter
      volume. Since patients with diabetic retinopathy had a smaller white matter
      volume, this suggests that cognitive decline is at least partly mediated by
      microvascular disease. This needs to be addressed in future studies.

PMID- 17546439
TI  - Comment on: Krabbe KS, Nielsen AR, Krogh-Madsen R et al (2007) Brain-derived
      neurotrophic factor (BDNF) and type 2 diabetes. Diabetologia 50:431-438.

PMID- 17546440
TI  - [Standards and perspectives for thromboembolism prophylaxis].
AB  - Thromboembolic complications are one of the most severe complications after
      orthopaedic or trauma surgery. More than 50% of patients undergoing total knee
      replacement are at risk of suffering deep-vein thrombosis if not provided
      sufficient prophylaxis. The former standard prophylaxis with unfractionated
      heparin has been changed over the few last years to low molecular weight heparin
      or heparinoids, due to the increased incidence of heparin-induced
      thrombocytopenia under therapy with unfractionated heparin. Risk management is
      based on different risk levels: highest risk, high risk, intermediate risk and
      low risk. The probabilities of suffering from deep-vein thrombosis have been
      determined dependent on the risk level. In patients with total knee replacement,
      which are at highest risk, a higher dose for the prevention of thromboembolism
      has been recommended. The synthetic, selective antithrombin-binding
      pentasaccharide fondaparinux has been successfully used in prophylaxis for the
      prevention of thrombosis in highest risk patients. However, because of a higher
      risk of bleeding, this pentasaccharide can be only given 6-8 h after surgery. Low
      molecular weight heparins and the pentasaccharide are the standard
      pharmacological prophylaxis for the prevention of venous thromboembolism.
      Physical therapy, pneumatic compression, A-V impulse systems, passive ankle
      motion systems and graduated compression stockings are an additional, effective
      prophylaxis without side effects.

PMID- 17546441
TI  - [The value of regional and general anaesthesia in orthopaedic surgery].
AB  - Adequate postoperative pain management is of major importance for a short
      rehabilitation time after painful orthopaedic surgery. Multimodal pathways have
      been established to achieve a surgical patient free of pain and complications.
      Peripheral and central nerve blocks are a fundamental part of these
      interdisciplinary strategies and are already implemented in orthopaedic surgical
      care. This article summarises the value of special anaesthetic techniques,
      especially regional anaesthesia, in orthopaedic surgery and discusses their
      impact on several postoperative outcome goals.

PMID- 17546443
TI  - The effect of sulfur compounds on H2 evolution/consumption reactions, mediated by
      various hydrogenases, in the purple sulfur bacterium, Thiocapsa roseopersicina.
AB  - The influence of reduced sulfur compounds (including stored S(0)) on H(2)
      evolution/consumption reactions in the purple sulfur bacterium, Thiocapsa
      roseopersicina BBS, was studied using mutants containing only one of the three
      known [NiFe] hydrogenase enzymes: Hox, Hup or Hyn. The observed effects depended
      on the kind of hydrogenase involved. The mutant harbouring Hox hydrogenase was
      able to use S(2)O (3) (2-) , SO (3) (2-) , S(2-) and S(0) as electron donors for
      light-dependent H(2) production. Dark H(2) evolution from organic substrates via
      Hox hydrogenase was inhibited by S(0). Under light conditions, endogenous H(2)
      uptake by Hox or Hup hydrogenases was suppressed by S compounds. CO(2)-dependent
      H(2) uptake by Hox hydrogenase in the light required the additional presence of S
      compounds, unlike the Hup-mediated process. Dark H(2) consumption via Hyn
      hydrogenase was connected to utilization of S(0) as an electron acceptor and
      resulted in the accumulation of H(2)S. In wild type BBS, with high levels of
      stored S(0), dark H(2) production from organic substrates was significantly
      lower, but H(2)S accumulation significantly higher, than in the mutant
      GB1121(Hox(+)). There is a possibility that H(2) produced via Hox hydrogenase is
      consumed by Hyn hydrogenase to reduce S(0).

PMID- 17546444
TI  - Contact angle measurements under thermodynamic equilibrium conditions.
AB  - The precise control of the ambient humidity during contact angle measurements is
      needed to obtain stable and valid data. For a such purpose, a simple low-cost
      device was designed, and several modified surfaces relevant to biosensor design
      were studied. Static contact angle values for these surfaces are lower than
      advancing contact angles published for ambient conditions, indicating that
      thermodynamic equilibrium conditions are needed to avoid drop evaporation during
      the measurements.

PMID- 17546445
TI  - UPLC-MS as a powerful technique for screening the nonvolatile contaminants in
      recycled PET.
AB  - The possibility of using recycled polyethylene terephthalate as a food contact
      material is being seriously considered, but the potential migration of
      nonvolatile compounds from it must be assessed to ensure that it is safe to do
      so. In the study presented here, four samples of recycled PET were each exposed
      to three food simulants under the harsh extraction conditions stipulated by
      European legislation regarding migration tests. The nonvolatile compounds that
      migrated from them were determined by ultra performance liquid chromatography
      mass spectrometry using three different cone voltages, and both positive and
      negative ionization modes. A total of 36 chemical compounds were detected, some
      of which were identified, including common additives such as N,N'-di-beta
      naphthyl-p-phenylenediamine (antioxidant) and 2,4-di-tert-butyl-6-(5-chloro-2H
      benzotriazol-2-yl)phenol (light stabilizer) as well as degradation compounds such
      as ethylene terephthalate dimers and trimers. In addition, specific migration
      values of three common components of polyethylene terephthalate (diethylene
      glycol, terephthalic acid, and isophthalic acid) were determined and found to
      occur at levels of <1 mg/kg-much lower than the specific migration limits
      stipulated by European legislation.

PMID- 17546446
TI  - Small organic molecular imprinted materials: their preparation and application.
AB  - Molecular imprinting is a technique for preparing polymeric materials that are
      capable of recognizing and binding the desired molecular target with a high
      affinity and selectivity. The materials can be applied to a wide range of target
      molecules, even those for which no natural binder exists or whose antibodies are
      difficult to raise. The imprinting of small organic molecules (e.g.,
      pharmaceuticals, pesticides, amino acids, steroids, and sugars) is now almost
      routine. In this review, we pay special attention to the synthesis and
      application of molecular imprinted polymer (MIPs) imprinted with small organic
      molecules, including herbicides, pesticides, and drugs. The advantages,
      applications, and recent developments in small organic molecular imprinted
      technology are highlighted.

PMID- 17546447
TI  - Analysis of heterocyclic aromatic amines.
AB  - Heterocyclic aromatic amines are formed in protein and amino acid-rich foods at
      temperatures above 150 degrees C. Of more than twenty heterocyclic aromatic
      amines identified ten have been shown to have carcinogenic potential. As
      nutritional hazards, their reliable determination in prepared food, their uptake
      and elimination in living organisms, including humans, and assessment of
      associated risks are important food-safety issues. The concentration in foods is
      normally in the low ng g(-1) range, which poses a challenge to the analytical
      chemist. Because of the complex nature of food matrixes, clean-up and enrichment
      of the extracts are also complex, usually involving both cation-exchange
      (propylsulfonic acid silica gel, PRS) and reversed-phase purification. The
      application of novel solid-phase extraction cartridges with a wettable apolar
      phase combined with cation-exchange characteristics simplified this process--both
      the polar and apolar heterocyclic aromatic amines were recovered in one fraction.
      Copper phthalocyanine trisulfonate bonded to cotton ("blue cotton") or rayon, and
      molecular imprinted polymers have also been successfully used for one-step sample
      clean-up. For analysis of the heterocyclic aromatic amines, liquid chromatography
      with base-deactivated reversed-phase columns has been used, and, recently, semi
      micro and capillary columns have been introduced. The photometric, fluorimetric,
      or electrochemical detectors used previously have been replaced by mass
      spectrometers. Increased specificity and sub-ppb sensitivities have been achieved
      by the use of the selected-reaction-monitoring mode of detection of advanced MS
      instrumentation, for example the triple quadrupole and Q-TOF instrument
      combination. Gas chromatography, also with mass-selective detection, has been
      used for specific applications; the extra derivatization step needed for
      volatilization has been balanced by the higher chromatographic resolution.

PMID- 17546448
TI  - Determination of lead in wine by hydride generation atomic fluorescence
      spectrometry in the presence of hexacyanoferrate(III).
AB  - A rapid, accurate, and precise method is described for the determination of Pb in
      wine using continuous-flow hydride generation atomic fluorescence spectrometry
      (CF-HGAFS). Sample pretreatment consists of ten-fold dilution of wine followed by
      direct plumbane generation in the presence of 0.1 mol L(-1) HCl and 1% m/v
      K(3)[Fe(CN)(6)] with 1% m/v NaBH(4) as reducing agent. An aqueous standard
      calibration curve is recommended for Pb quantification in wine sample. The method
      provides a limit of detection and a limit of quantification of 0.3 microg L(-1)
      and 1 microg L(-1), respectively. The relative standard deviation varies between
      2-6% (within-run) and 4-11% (between-run) at 3-30 microg L(-1) Pb levels in wine.
      Good agreement has been demonstrated between results obtained by CF-HGAFS and
      direct electrothermal atomic absorption spectrometry in analyses of red and white
      wines within the concentration range of 9.2-25.8 microg L(-1) Pb.

PMID- 17546449
TI  - Increased anisotropy in neonatal meningitis: an indicator of meningeal
      inflammation.
AB  - INTRODUCTION: Increased anisotropy in brain abscesses has been shown to be due to
      adhesion of inflammatory cells and is suggestive of an active inflammatory
      process. The objective of this study was to determine if similar changes occur in
      the pia-arachnoid on the surface of the cerebral cortex in patients with pyogenic
      meningitis, and if these changes regress following antibiotic therapy. METHODS:
      Diffusion tensor imaging (DTI) was performed on 14 term neonates (mean age 13
      days) with bacterial meningitis and 10 healthy age- and sex-matched controls.
      Regions of interest (ROIs) were placed on areas including the leptomeninges, the
      cerebral cortex and adjoining subcortical white matter for quantitation of mean
      fractional anisotropy (FA) and diffusivity (MD) values. Follow-up MRI was
      performed in five of the neonates in the patient group after 2 weeks of
      antibiotic treatment. FA and MD values were compared in patients before and after
      antibiotic treatment as well as with those in the healthy controls. RESULTS:
      Significantly higher FA values but no difference in MD values were observed in
      the patient group as compared to the healthy controls at both time points (before
      and after antibiotic treatment). Significantly decreased FA values in the
      frontal, occipital and temporal cortical regions were observed in patients
      following antibiotic treatment. CONCLUSION: DTI-derived FA may be of value in the
      noninvasive assessment of meningeal inflammatory activity and treatment response
      in neonates.

PMID- 17546450
TI  - The neural network involved in a bimanual tactile-tactile matching discrimination
      task: a functional imaging study at 3 T.
AB  - INTRODUCTION: The cerebral and cerebellar network involved in a bimanual object
      recognition was studied in blood oxygenation dependent level functional magnetic
      resonance imaging (fMRI). METHODS: Nine healthy right-handed volunteers were
      scanned (1) while performing bilateral finger movements (nondiscrimination motor
      task), and (2) while performing a bimanual tactile-tactile matching
      discrimination task using small chess pieces (tactile discrimination task).
      RESULTS: Extensive activations were specifically observed in the parietal (SII,
      superior lateral lobule), insular, prefrontal, cingulate and neocerebellar
      cortices (HVIII), with a left predominance in motor areas, during the tactile
      discrimination task in contrast to the findings during the nondiscrimination
      motor task. CONCLUSION: Bimanual tactile-tactile matching discrimination recruits
      multiple sensorimotor and associative cerebral and neocerebellar networks
      (including the cerebellar second homunculus, HVIII), comparable to the neural
      circuits involved in unimanual tactile object recognition.

PMID- 17546451
TI  - Bilateral renal venous thrombosis and adrenal hemorrhage: sequential prenatal US
      with postnatal recovery.
AB  - A neonate presented with bilateral renal venous thrombosis (RVT) and adrenal
      hemorrhage. Serial fetal ultrasonography showed progressive development of severe
      atrophy of one kidney and mild atrophy of the other. At sequential postnatal
      imaging, both kidneys showed progressive growth. Bilateral fetal RVT is quite
      uncommon, and postnatal recovery of a kidney severely affected by RVT is very
      rare.

PMID- 17546452
TI  - Mesenteric lymphatic malformation.

PMID- 17546453
TI  - An analysis of the physiological FDG uptake in the stomach with the water gastric
      distention method.
AB  - PURPOSE: Physiological FDG uptake in the stomach is a common phenomenon,
      especially noted at the cardia. Water intake just before scanning will result in
      gastric distention and thinning of the gastric wall, which in turn may lead to a
      reduction in the physiological uptake in the gastric wall. In the current study,
      we investigated whether gastric distention by water intake just before PET
      imaging reduces physiological FDG uptake in the stomach. METHODS: The patient
      population comprised 60 patients who underwent whole-body FDG-PET imaging for
      cancer screening following gastroscopy performed within the preceding week. All
      patients took 400 ml of water for hydration and were administered 185 MBq of FDG
      intravenously. The patients were randomly divided into two groups: a group with
      additional water intake (AW group; n = 30) and a group without additional water
      intake (NW group; n = 30). In the AW group, an additional 400 ml of water was
      given just before PET imaging. For quantitative analysis, the stomach was
      classified into three areas [upper (U), middle (M) and lower (L)], and the degree
      of FDG uptake in each area was evaluated using standardised uptake values (SUVs).
      RESULTS: In the NW group, the mean SUVs in the U, M and L areas were 2.41 +/-
      0.75, 2.28 +/- 0.73 and 1.61 +/- 0.89, respectively, while in the AW group they
      were 1.82 +/- 0.66, 1.73 +/- 0.56 and 1.48 +/- 0.49, respectively, and 2.21 +/-
      0.38 in the oesophago-gastric junction. The mean SUVs in the U and M areas in the
      AW group were significantly lower than those in the NW group (p < 0.05).
      CONCLUSION: Additional water intake just before PET imaging is an effective
      method for suppressing physiological FDG uptake in the stomach.

PMID- 17546454
TI  - PET/CT demonstrates increased myocardial FDG uptake following irradiation
      therapy.

PMID- 17546455
TI  - Intense [18F]FDG tongue uptake in a case of acipimox-related angio-oedema during
      FDG-PET myocardial viability study.

PMID- 17546456
TI  - Somatostatin receptor subtype 2-mediated uptake of radiolabelled somatostatin
      analogues in the human kidney.
AB  - PURPOSE: Renal irradiation is a dose-limiting factor in peptide receptor
      radionuclide therapy using radiolabelled somatostatin analogues. This irradiation
      is mainly caused by reabsorption of radiolabelled peptides in the proximal
      tubule. In the human kidney, somatostatin receptors are expressed in the vasa
      recta, tubuli and glomeruli. It is not clear to what extent these receptors
      contribute to the total kidney radioactivity uptake. METHODS: Retrospectively,
      [(111)In-DTPA(0)]octreotide scans of ten selected patients with carcinoids (well
      differentiated gastrointestinal endocrine tumour) with liver metastases were
      evaluated. For each patient, two scans were obtained: one scan was performed
      without (control) and one during treatment with unlabelled octreotide. Kidney,
      tumour, spleen and liver uptake was measured in both scans. RESULTS: The interval
      between the two scans per patient varied from 50 to 397 days. Octreotide
      treatment substantially lowered kidney [(111)In-DTPA(0)]octreotide uptake in
      eight out of ten patients. Kidney uptake in all patients was reduced to 82%+/-15%
      of control, (p < 0.01). A correlation between kidney uptake and spleen uptake was
      found (r=0.67, p < 0.05). Serum creatinine was unchanged. Surprisingly, tumour
      and liver [(111)In-DTPA(0)]octreotide uptake was not significantly influenced by
      unlabelled octreotide therapy, but spleen uptake was significantly lowered by
      treatment (30.6% of control, p < 0.002). CONCLUSION: We conclude that the
      somatostatin receptor plays a role in the total renal uptake of radiolabelled
      somatostatin analogues. The long interval between scans might explain the finding
      that tumour and liver metastasis uptake of [(111)In-DTPA(0)]octreotide was
      unchanged. Further studies are needed to confirm and eludicate the results of
      this study.

PMID- 17546457
TI  - PET probes and oncological surgery: a productive new marriage for nuclear
      medicine?

PMID- 17546458
TI  - Visual acuity of the midland banded water snake estimated from evoked
      telencephalic potentials.
AB  - The visual acuity of seven midland banded water snakes was measured by recording
      evoked responses from telencephalon to temporally modulated square wave grating
      patterns. Using conventional electrophysiological techniques and signal
      averaging, high contrast square wave gratings of different spatial frequencies
      were presented. Acuity was estimated by extrapolating relative response
      amplitude/log(10) spatial frequency functions which yielded an average acuity of
      4.25 cycles/degree. Refractive state was also estimated by recording evoked
      potentials to intermediate spatial frequencies with different lenses in front of
      the eye. Polynomial fits indicated that under the experimental conditions the
      snakes were around 6.4 diopters hyperopic suggesting a corrected acuity of 4.89
      cycles/degree. Reduction of grating luminance resulted in a reduction in evoked
      potential acuity measurements. These results indicate that the spatial resolution
      of midland banded water snakes is the equal of cat; about 20/120 in human
      clinical terms.

PMID- 17546459
TI  - Expiratory muscle fatigue impairs exercise performance.
AB  - High-intensity, exhaustive exercise may lead to inspiratory as well as expiratory
      muscle fatigue (EMF). Induction of inspiratory muscle fatigue (IMF) before
      exercise has been shown to impair subsequent exercise performance. The purpose of
      the present study was to determine whether induction of EMF also affects
      subsequent exercise performance. Twelve healthy young men performed five 12-min
      running tests on a 400-m track on separate days: a preliminary trial, two trials
      after induction of EMF, and two trials without prior muscle fatigue. Tests with
      and without prior EMF were performed in an alternate order, randomly starting
      with either type. EMF was defined as a >or=20% drop in maximal expiratory mouth
      pressure achieved during expiratory resistive breathing against 50% maximal
      expiratory mouth pressure. The average distance covered in 12 min was
      significantly smaller during exercise with prior EMF compared to control exercise
      (2872+/-256 vs. 2957+/-325 m; P=0.002). Running speed was consistently lower
      (0.13 m s(-1)) throughout the entire 12 min of exercise with prior EMF. A
      significant correlation was observed between the level of EMF (decrement in
      maximal expiratory mouth pressure after resistive breathing) and the reduction in
      running distance (r2=0.528, P=0.007). Perceived respiratory exertion was higher
      during the first 800 m and heart rate was lower throughout the entire test of
      running with prior EMF compared to control exercise (5.3+/-1.6 vs. 4.5+/-1.7
      points, P=0.002; 173+/-10 vs. 178+/-7 beats min(-1), P=0.005). We conclude that
      EMF impairs exercise performance as previously reported for IMF.

PMID- 17546460
TI  - Effect of transcutaneous electrical acupoint stimulation on fatigue recovery of
      the quadriceps.
AB  - The aim of this study was to evaluate the effect of transcutaneous electrical
      acupoint stimulation (TEAS) at selected acupoints on enhancing the rate of muscle
      force recovery after strenuous knee extension/flexion exercise. Ten male and
      seven female healthy young adults participated in this study in which they
      performed isokinetic knee fatigue exercise on the Biodex System 3 ergometer on
      three separate days. After the familiarization trial on day 1, subjects underwent
      15 min of either TEAS or pseudo-TEAS recovery treatment after the isokinetic
      exercise in the following two trials on days 2 and 3, respectively. The TEAS
      treatment was applied on four selected acupoints [Zusanli (ST36), Chenshan
      (BL57), Yanglingquan (GB34) and Sanyinjiao (SP6)] while the pseudo-TEAS treatment
      was applied to the points away from the true acupoints. Isometric knee extension
      peak torque was measured before and immediately after the test exercise, and
      again during the 15-min recovery period at 5-min intervals. Blood lactate and
      median power frequency (MF) of the vastus medialis, vastus lateralis and rectus
      femoris were also measured at the same time points. The results indicated that
      the TEAS treatment was significantly more effective than the pseudo-TEAS
      treatment in enhancing the rate of muscle force recovery (knee extension peak
      torque recovery after 15 min, from 155 to 195 Nm in TEAS group and from 155 to
      182 Nm in the pseudo-TEAS group), but had no effect on lactate removal and MF
      restitution rate. It is proposed that pain control is a plausible mechanism to
      explain the benefit of TEAS treatment. As TEAS is a non-invasive and simple
      treatment, it is feasible to apply it during and immediately after training.

PMID- 17546461
TI  - Intraoperative biliary exploration through the left hepatic duct orifice during
      left hepatectomy in patients with left-sided hepatolithiasis.
AB  - BACKGROUND AND AIMS: Left-sided hepatolithiasis often requires left hepatectomy
      and exploration of the common bile duct and right hepatic duct. The aim of this
      study was to assess the feasibility of alternative method of bile duct
      exploration other than choledochotomy. MATERIALS AND METHODS: A prospective study
      involving 50 cases of left hepatectomy for left or bilateral intrahepatic stone
      was performed. Left hepatic duct (LHD) orifice was used as primary access route
      for biliary exploration. Choledochotomy was performed only for large common bile
      duct stones, variant bile duct anatomy, or intentional T-tube insertion for later
      removal of residual stones. RESULTS: In 44 patients with left-sided
      hepatolithiasis, biliary exploration through LHD orifice was performed in 40
      (90.9%); T-tube choledochotomy was required in three (9.1%). There was neither
      residual stone nor major surgical complication except infection, and recurrence
      occurred in one patient during mean follow-up of 32 months. On the other hand, T
      tube choledochotomy was performed in three of six patients with bilateral
      hepatolithiasis (50%). Three patients had residual stones, and two of them were
      treated by cholangioscopy through the T-tube tract. Recurrence occurred in two
      patients. CONCLUSION: We think that intraoperative biliary exploration through
      LHD orifice in left-sided hepatolithiasis patients is an effective approach
      simplifying the operation procedure by avoiding choledochotomy and subsequent T
      tube insertion.

PMID- 17546462
TI  - The impact of stimulus-specific practice and task instructions on response
      congruency effects between tasks.
AB  - In task switching experiments participants have to respond to the same set of
      stimuli while task instructions vary (e.g., digit stimuli are assigned to left-
      or right-sided key presses by means of magnitude vs. parity classification).
      Response congruency effects denote worse performance for a stimulus, which is
      associated with different responses in the two tasks as compared to a stimulus,
      which is associated with the same response. Previous research suggests that such
      effects reflect direct links between stimuli and responses acquired in the course
      of experimental practice. In the current study we investigated the impact of
      stimulus-specific practice and task instruction by reversing the S-R mapping of
      one task (Experiment 1) or replacing one task with a new one (Experiment 2) in
      the second half of an experimental session. Consistent with the direct link
      account, S-R links practiced during the first half of the experiment largely
      determined congruency effects despite altered task instructions. Furthermore, the
      results suggest that previously practiced S-R links (a) can be relatively quickly
      overwritten by practicing a novel S-R mapping, and (b) are subject to passive
      decay when no longer in use.

PMID- 17546463
TI  - High prevalence of molecular markers for resistance to chloroquine and
      pyrimethamine in Plasmodium falciparum from Zimbabwe.
AB  - Chloroquine has been the first line drug of treatment for malaria in Zimbabwe
      until a recent adoption of an interim policy to treat using a combination of
      chloroquine (CQ) and sulfadoxine/pyrimethamine (SP). We examined the prevalence
      of parasites with mutations associated with resistance to the drug combination in
      three areas that have been previously described to differ in malaria endemicity.
      Our results show that the parasite population from the three areas had a high
      prevalence of molecular markers of resistance to chloroquine and pyrimethamine.
      The prevalence of crt (K76T) was 64, 82, and 92% for Chiredzi, Kariba, and
      Bindura, respectively. On the dhfr locus, the presence of triple mutations
      (codons 51, 59, and 108) was approximately 50% for all the three locations. On
      the other hand, the prevalence of dhps mutations (codons 436, 437, and 540) was
      low accounting for less than 20% in all the areas. Studies reported here
      demonstrate widespread prevalence of molecular markers associated with
      chloroquine and pyrimethamine resistance and should be taken into consideration
      for further refinement of malaria control strategies in Zimbabwe. The design and
      implementation of successful control strategies would benefit from understanding
      the prevalence of mutations associated with drug resistance in parasite
      populations.

PMID- 17546464
TI  - Mitochondrial disruption and DNA fragmentation in Trypanosoma cruzi induced by
      naphthoimidazoles synthesized from beta-lapachone.
AB  - Three naphthoimidazoles presenting aromatic groups attached to the imidazole ring
      were the most active against trypomastigotes of Trypanosoma cruzi between 45
      derivatives from beta-lapachone. N1 is active against the three forms of the
      parasite. In this work, we investigated N2 and N3 and analyzed the effect of the
      three derivatives on metacyclogenesis, endocytosis, and cell cycle. In
      epimastigotes, N2 and N3 blocked the cell cycle, inhibited succinate cytochrome c
      reductase, metacyclogenesis, and induced damage to mitochondrion, Golgi, and
      reservosomes. In treated trypomastigotes, there were alterations in the
      mitochondrion, nucleus and kinetoplast, and DNA fragmentation. Preincubation with
      cysteine protease inhibitors reversed the effect of N1, N2, and N3. Such
      reversion and ultrastructural alterations suggest the involvement of autophagy in
      parasite death. Ultrastructural, flow cytometry, and biochemical studies suggest
      that naphthoimidazoles interferes with the energetic metabolism and induces DNA
      fragmentation.

PMID- 17546465
TI  - Common genetic variation in eight genes of the GH/IGF1 axis does not contribute
      to adult height variation.
AB  - Stature (adult height) is one of the most heritable human traits, yet few genes,
      if any, have been convincingly associated with adult height variation in the
      general population. Here, we selected 150 tag SNPs from eight candidate genes in
      the growth hormone (GH)/insulin-like growth factor-1 (IGF1) axis (GHR, GHRH,
      GHRHR, IGF1, IGFALS, IGFBP3, JAK2, STAT5B), and genotyped them in approximately
      2,200 individuals ascertained for short or tall stature. Nominally significant
      tag SNPs were then tested in three additional replication cohorts, including a
      family-based panel to rule out spurious associations owing to population
      stratification. Across the four height cohorts (N = 6,075 individuals), we did
      not observe any consistent associations between stature and common variants (> or
      =5% minor allele frequency) in these eight genes, including a common deletion of
      the growth hormone receptor gene exon 3. Tests of epistatic interactions between
      these genes did not yield any results beyond those expected by chance. Although
      we have not tested all genes in the GH/IGF1 axis, our results indicate that
      common variation in these GH/IGF1 axis genes is not a major determinant of
      stature, and suggest that if common variation contributes to adult height
      variation in the general population, the variants are in other, possibly
      unanticipated genes.

PMID- 17546466
TI  - Grasshopper (Orthoptera: Acrididae) communities respond to fire, bison grazing
      and weather in North American tallgrass prairie: a long-term study.
AB  - Because both intrinsic and extrinsic factors influence insect population
      dynamics, operating at a range of temporal and spatial scales, it is difficult to
      assess their contributions. Long-term studies are ideal for assessing the
      relative contributions of multiple factors to abundance and community dynamics.
      Using data spanning 25 years, we investigate the contributions of weather at
      annual and decadal scales, fire return interval, and grazing by bison to
      understand the dynamics of abundance and community composition in grasshopper
      assemblages from North American continental grassland. Each of these three
      primary drivers of grassland ecosystem dynamics affects grasshopper population
      and community dynamics. Negative feedbacks in abundances, as expected for
      regulated populations, were observed for all feeding guilds of grasshoppers.
      Abundance of grasshoppers did not vary in response to frequency of prescribed
      burns at the site. Among watersheds that varied with respect to controlled spring
      burns and grazing by bison, species composition of grasshopper assemblages
      responded significantly to both after 25 years. However, after more than 20 years
      of fire and grazing treatments, the number of years since the last fire was more
      important than the managed long-term fire frequency per se. Yearly shifts in
      species composition (1983-2005), examined using non-metric multidimensional
      scaling and fourth-corner analysis, were best explained by local weather events
      occurring early in grasshopper life cycles. Large-scale patterns were represented
      by the Palmer Drought Severity Index and the North Atlantic Oscillation (NAO).
      The NAO was significantly correlated with annual mean frequencies of
      grasshoppers, especially for forb- and mixed-feeding species. Primary grassland
      drivers-fire, grazing and weather-contributing both intrinsic and extrinsic
      influences modulate long-term fluctuations in grasshopper abundances and
      community taxonomic composition.

PMID- 17546467
TI  - Ligand-induced monomerization of Allochromatium vinosum cytochrome c' studied
      using native mass spectrometry and fluorescence resonance energy transfer.
AB  - Cytochrome c' from Allochromatium vinosum is an attractive model protein to study
      ligand-induced conformational changes. This homodimeric protein dissociates into
      monomers upon binding of NO, CO or CN(-) to the iron of its covalently attached
      heme group. While ligand binding to the heme has been well characterized using a
      variety of spectroscopic techniques, direct monitoring of the subsequent
      monomerization has not been reported previously. Here we have explored two
      biophysical techniques to simultaneously monitor ligand binding and
      monomerization. Native mass spectrometry allowed the detection of the dimeric and
      monomeric forms of cytochrome c' and even showed the presence of a CO-bound
      monomer. The kinetics of the ligand-induced monomerization were found to be
      significantly enhanced in the gas phase compared with the kinetics in solution,
      however. Ligand binding to the heme and the dissociation of the dimer in solution
      were also studied using energy transfer from a fluorescent probe to both heme
      groups of the protein. Comparison of ligand binding kinetics as observed with UV
      vis spectroscopy with changes in fluorescence suggested that binding of one CO
      molecule per dimer could be sufficient for monomerization.

PMID- 17546468
TI  - Density functional theory and molecular dynamics investigations on substituted
      banana-shaped compounds.
AB  - Density functional theory (DFT) calculations and molecular dynamics (MD)
      simulations on the atomic level were performed on three different substituted
      banana-shaped compounds derived from 1,3-phenylene bis[4-(4-n
      hexyloxyphenyliminomethyl)benzoate] (P-6-O-PIMB). The DFT studies were carried
      out on the isolated molecules, and in the MD simulations clusters were treated
      with up to 64 monomers. The effect of polar substituents, such as chlorine and
      the nitro group, on the central 1,3-phenylene unit of banana-shaped compounds was
      investigated. In particular, flexibility, polarity, electrostatic potential (ESP)
      group charge distributions, B-factors, bending angles and molecular lengths were
      considered. The MD results were analysed by trajectories of significant torsion
      angles as well as order parameters such as radial atom pair distribution
      functions g(r), orientational correlation functions g(o), diffusion coefficients
      (D) and root mean square deviations (RMSD) values. The g(r) and g(o) values show
      that a certain long range order is generated by the introduction of a NO(2) group
      in the 2-position of the central 1,3-phenylene ring. In contrast, the
      chlorination at the 4 and 6 positions of the central 1,3-phenylene unit decreases
      the long range order tendency by its perturbation effect on the conformations in
      such molecules. Moreover, g(r) and g(o) values, as well as diffusion
      coefficients, show that in the NO(2) substituted compound the formation of
      microphase areas is preferred. Finally, the aggregation effect in such compounds
      was studied in a systematic way by a comparison of the conformational properties
      of the isolated molecules and the monomers in the clusters.

PMID- 17546469
TI  - Dietary lipids impacts on healthy ageing.
AB  - Healthy ageing is gaining attention in the lipid nutrition field. As in vivo
      biomarkers of healthy ageing, we have evaluated the survival, learning/memory
      performance, and physical potencies in rodents fed a diet supplemented with high
      linoleic acid (LNA, omega6) safflower oil or high-alpha-linolenic acid (ALA,
      omega3) perilla oil for long periods. The results suggested that perilla oil with
      a low omega6/omega3 ratio is beneficial for healthy ageing. In order to address
      this issue further, we determined the survival of stroke-prone SHR (SHRSP) rats
      fed a conventional rodent diet supplemented with 10% fat or oil. Survival was
      longer with omega3-rich oils compared with omega6-rich oils. However, some kinds
      of vegetable oils and hydrogenated oils shortened the survival of SHRSP rats to
      an unusual degree (ca. 40% compared with that of omega6-rich oil) that could not
      be accounted for by the fatty acid and phytosterol composition of the oils. The
      observed decrease in platelet counts was associated with pathological changes in
      the kidney and other organs. Dihydro-vitamin K1 is proposed as a likely candidate
      as a stroke-stimulating factor in hydrogenated oils. Thus, factors other than
      fatty acids (omega6/omega3 balance) and phytosterols must be taken into account
      when fats and oils are evaluated in relation to healthy ageing.

PMID- 17546470
TI  - A Bayesian model unifies multisensory spatial localization with the physiological
      properties of the superior colliculus.
AB  - "Multisensory integration" refers to the phenomenon by which information from
      different senses is integrated in order to interpret and guide responses to
      external events. Here, we advance two specific hypotheses: (1) the process of
      multisensory integration in spatial localization is statistically optimal, and
      (2) the optimality of the processes guiding this localization results from the
      implementation of Bayes' rule. We explicitly test the predictions of an optimal
      (Bayesian) model for the behavior of animals trained and tested in a spatial
      localization task, and find that the model correctly predicts behavioral patterns
      which are at times counterintuitive. The model also predicts the receptive field
      properties of superior colliculus neurons that are involved in these behaviors,
      and sheds new light on the computational responsibilities different circuits have
      in effecting these behaviors. Thus, the Bayesian model appears to represent not
      only a yardstick for the optimality of a behavior, but also a descriptor of the
      underlying neural processes.

PMID- 17546471
TI  - Enhanced stability of heterologous proteins by supramolecular self-assembly.
AB  - Recently, we reported on the dual function of human ferritin heavy chain (hFTN-H)
      used for the fusion expression and solubility enhancement of various heterologous
      proteins: (1) high-affinity interaction with HSP70 chaperone DnaK and (2)
      formation of self-assembled supramolecules with limited and constant sizes.
      Especially the latter, the self-assembly function of hFTN-H is highly useful in
      avoiding the undesirable formation of insoluble macroaggregates of heterologous
      proteins in bacterial cytoplasm. In this study, using enhanced green fluorescent
      protein (eGFP) and several deletion mutants of Mycoplasma arginine deiminase
      (ADI(132-410)) as reporter proteins, we confirmed through TEM image analysis that
      the recombinant fusion proteins (hFTN-H::eGFP and hFTN-H::ADI(132-410)) formed
      intracellular spherical particles with nanoscale diameter ( approximately 10 nm),
      i.e., noncovalently cross-linked supramolecules. Surprisingly, the supramolecular
      eGFP and ADI showed much enhanced stability in bioactivity. That is, the activity
      level was much more stably maintained for the prolonged period of time even at
      high temperature, at high concentration of Gdn-HCl, and in wide range of pH. The
      stability enhancement by supramolecular self-assembly may make it possible to
      utilize the protein supramolecules as novel means for drug delivery, enzymatic
      material conversion (biotransformation), protein chip/sensor, etc. where the
      maintenance of protein/enzyme stability is strictly required.

PMID- 17546472
TI  - An azoreductase, aerobic NADH-dependent flavoprotein discovered from Bacillus
      sp.: functional expression and enzymatic characterization.
AB  - The gene coding for an azoreductase, designated as an azrA, was cloned by
      polymerase chain reaction amplification from the genomic DNA of Bacillus sp.
      strain B29 isolated from soil. The azrA encoded a protein of 208 amino acids with
      calculated molecular mass of 22,766 Da. The enzyme was heterologously expressed
      in Escherichia coli with a strong band of 23 kDa on sodium dodecyl sulfate
      polyacrylamide gel electrophoresis. Purified recombinant AzrA was a homodimer
      with a native molecular mass of 48 kDa containing two molecules of flavin
      mononucleotide (FMN; oxidized). This activity was oxygen insensitive and was
      nicotinamide adenine dinucleotide (reduced form; NADH) dependent. Recombinant
      AzrA exhibited a broad pH stability between 6 and 10 with a temperature optimum
      of 60-80 degrees C. The enzyme cleaved the model azo compound of methyl red [MR,
      4'-(dimethylamino)-azobenzene-2-carboxylic acid] into 2-aminobenzoic acid and N,
      N'-dimethyl-p-phenylenediamine by ping-pong mechanism. The enzyme was not only
      able to decolorize MR but also able to decolorize sulfonated azo dyes such as
      Orange I and Acid Red 88.

PMID- 17546474
TI  - Prognostic factors in primary gastric lymphoma.
AB  - BACKGROUND: There is not a gold standard in the treatment of primary gastric
      lymphoma (PGL). This study aimed to establish prognostic factors that should be
      considered for the staging and management of this disease. METHODS: We
      retrospectively reviewed and analyzed the clinicopathological features of
      patients treated for PGL in a tertiary referral center in Mexico City in a 10
      year period from 1990 through 2000. Staging was performed with the Ann-Arbor
      system. Overall and disease-free survivals were the primary endpoints. RESULTS:
      We identified 41 patients of which 19 (46.3%) were classified as large-cell
      lymphoma, 16 (39.0%) as low-grade MALT, and 6 (14.6%) patients as lymphoma
      unspecified. The series included 15 (36.6%) patients with stage IV disease.
      Twenty patients (48.8%) underwent surgery and 34 (82.1%) received chemotherapy.
      Twenty-three patients were treated with at least two different types of therapy
      (56.1%). Actuarial 1 and 5 years survival were 77.8 and 71.2%, respectively.
      Early stage at presentation, surgery, normal lactic dehydrogenase (LDH) levels
      and good performance status were associated with longer survival in univariate
      analysis. Only normal LDH and good performance status retained their significance
      in multivariate analysis. Regarding disease-free survival in multivariate
      analysis, only normal LDH was associated with a better prognosis: 131 versus 12
      months for LDH <197 and >or=197 mg/dl, respectively (P < 0.0001). CONCLUSIONS:
      Optimal treatment of PGL remains controversial. High LDH levels and poor
      performance status at diagnosis are associated with shorter overall and disease
      free survival and should be considered for the staging and management of these
      patients.

PMID- 17546475
TI  - Fractional reproduction-dispersal equations and heavy tail dispersal kernels.
AB  - Reproduction-Dispersal equations, called reaction-diffusion equations in the
      physics literature, model the growth and spreading of biological species. Integro
      Difference equations were introduced to address the shortcomings of this model,
      since the dispersal of invasive species is often more widespread than what the
      classical RD model predicts. In this paper, we extend the RD model, replacing the
      classical second derivative dispersal term by a fractional derivative of order
      1<alpha</=2. Fractional derivative models are used in physics to model anomalous
      super-diffusion, where a cloud of particles spreads faster than the classical
      diffusion model predicts. This paper also establishes a connection between the
      new RD model and a corresponding ID equation with a heavy tail dispersal kernel.
      The general theory developed here accommodates a wide variety of infinitely
      divisible dispersal kernels that adapt to any scale. Each one corresponds to a
      generalised RD model with a different dispersal operator. The connection
      established here between RD and ID equations can also be exploited to generate
      convergent numerical solutions of RD equations along with explicit error bounds.

PMID- 17546476
TI  - Coalescent size versus coalescent time with strong selection.
AB  - This work studies the coalescent (ancestral pedigree, genealogy) of the entire
      population. The coalescent structure (topology) is robust, but selection changes
      the rate of coalescence (the time between branching events). The change in the
      rate of coalescence is not uniform, rather the reduction in the time between
      branching events is greatest when the coalescent is small (immediately after the
      common ancestor is the only member of the coalescent) with little change when the
      coalescent is large (immediately preceding when that common ancestor becomes
      fixed and the size of the coalescent is N). This provides that the reduction in
      the coalescent time due to selection is much greater than the reduction in the
      cumulative size of the coalescent (total number of ancestors of the present
      population after and including the most recent common ancestor) due to selection.
      If Ns>>1, the coalescent and fixation times are approximately equal to [Formula:
      see text] , which is much less than the value N which would result from neutral
      drift (N rather than the canonical haploid neutral fixation time 2N is the
      appropriate comparison for the model considered here), in particular, it is 70%
      less for Ns=10 and 95% less for Ns=100. However, for those values of Ns, and N
      ranging between 10(3) and 10(6), the reduction in the cumulative size of the
      coalescent of the entire population compared to the neutral case ranges from 17%
      to 65% (depending on the values of N and s). The coalescent time for two
      individuals for Ns of 10 and 100 is reduced by approximately 70% and 94%,
      respectively, compared with the neutral case. Because heterozygosity is
      proportional to the coalescent time for two individuals and the number of
      segregating alleles is proportional to the cumulative size of the coalescent,
      selection reduces heterozygosity more than it reduces the number of segregating
      alleles.

PMID- 17546477
TI  - The impact of the 2004-2005 influenza vaccine shortage in the Veterans Health
      Administration.
AB  - BACKGROUND: The Veterans Health Administration (VHA) serves a population at high
      risk of influenza-related morbidity and mortality. The national public health
      response to the vaccine shortage of the 2004-2005 season resulted in
      prioritization of recipients and redistribution of available supply. OBJECTIVE:
      To characterize the impact of the 2004-2005 influenza vaccine shortage on
      vaccination among users of VHA facilities. DESIGN: Analysis using data from the
      cross-sectional VHA Survey of Healthcare Experiences of Patients. PARTICIPANTS:
      Outpatients seen in VHA clinics during the months September 2004-March 2005.
      MEASUREMENTS: Sociodemographics, vaccination prevalence, setting of vaccination,
      and reasons cited for not getting vaccinated. RESULTS: Influenza vaccination
      prevalence among VHA outpatients aged 50-64 was 56% and for those aged > or = 65
      was 86%. Compared to the 2 previous seasons, this estimate was lower for patients
      age 50-64 but similar for patients > or = 65. After adjustment for patient
      characteristics, unvaccinated patients aged 50-64 were 8.3 (95% CI 6.0, 11.4)
      times as likely to cite that they were told they were not eligible for
      vaccination because of the national shortage compared to patients > or = 65.
      Regional VHA variation in vaccination receipt and shortage-related reasons for
      nonvaccination was small. CONCLUSIONS: The national influenza vaccine shortage of
      2004-2005 primarily affected VHA users aged 50-64, consistent with the tiered
      prioritization guidance issued by the Centers for Disease Control and Prevention
      and Advisory Committee on Immunization Practices. Despite the shortage,
      vaccination prevalence among VHA users > or = 65 remained high.

PMID- 17546478
TI  - Prevalence of vitamin D deficiency in uninsured women.
AB  - BACKGROUND: Vitamin D deficiency, an important risk factor for osteoporosis and
      other chronic medical conditions, is epidemic in the United States. Uninsured
      women may be at an even higher risk for vitamin D deficiency than others owing to
      low intake of dietary and supplemental vitamin D and limited sun exposure.
      OBJECTIVE: Our goal was to determine the prevalence of vitamin D deficiency in
      this vulnerable population. SETTING AND PARTICIPANTS: We enrolled 145 uninsured
      women at a County Free Medical Clinic in urban Michigan. Questionnaires were used
      to obtain information about demographics, medical history, vitamin
      supplementation, sunlight exposure, and dietary vitamin D intake. RESULTS: The 96
      women who were tested for vitamin D status ranged in age from 21 to 65 years
      (mean 48 +/- 11), and 67% were vitamin D deficient as indicated by a 25
      hydroxyvitamin D [25(OH)D)] level <50 nmol/L (20 ng/mL). Non-Caucasians were 3
      times more likely than Caucasians to be vitamin D deficient (P = .049). Mean
      dietary vitamin D intake was low (125 +/- 109 IU/d) and only 24% of the
      participants used any supplemental vitamin D. Participants with total vitamin D
      intake <400 IU/day from diet and supplements were 10 times more likely to be
      vitamin D deficient than others (P < .001). CONCLUSIONS: These results
      demonstrate a high prevalence of vitamin D deficiency in an uninsured, medically
      underserved female population. Uninsured women should be strongly encouraged to
      increase their vitamin D intake.

PMID- 17546479
TI  - Gallstones containing bacteria are biofilms: bacterial slime production and
      ability to form pigment solids determines infection severity and bacteremia.
AB  - OBJECTIVE: Gallstone bacteria provide a reservoir for biliary infections. Slime
      production facilitates adherence, whereas beta-glucuronidase and phospholipase
      generate colonization surface. These factors facilitate gallstone formation, but
      their influence on infection severity is unknown. METHODS: Two hundred ninety-two
      patients were studied. Gallstones, bile, and blood (as applicable) were cultured.
      Bacteria were tested for beta-glucuronidase/phospholipase production and
      quantitative slime production. Infection severity was correlated with bacterial
      factors. RESULTS: Bacteria were present in 43% of cases, 13% with bacteremia.
      Severe infections correlated directly with beta-glucuronidase/phospholipase (55%
      with vs 13% without, P < 0.0001), but inversely with slime production (55 vs 8%,
      slime <75 or >75, P = 0.008). Low slime production and beta
      glucuronidase/phospholipase production were additive: Severe infections were
      present in 76% with both, but 10% with either or none (P < 0.0001). beta
      Glucuronidase/phospholipase production facilitated bactibilia (86% with vs 62%
      without, P = 0.03). Slime production was 19 (+/-8) vs 50 (+/-10) for bacteria
      that did or did not cause bacteremia (P = 0.004). No bacteria with slime >75
      demonstrated bacteremia. CONCLUSIONS: Bacteria-laden gallstones are biofilms
      whose characteristics influence illness severity. Factors creating colonization
      surface (beta-glucuronidase/phospholipase) facilitated bacteremia and severe
      infections; but abundant slime production, while facilitating colonization,
      inhibited detachment and cholangiovenous reflux. This shows how properties of the
      gallstone biofilm determine the severity of the associated illness.

PMID- 17546480
TI  - Religious characteristics and the death penalty.
AB  - Using one mock trial scenario, this study investigated whether religious and
      demographic factors were related to death penalty attitudes and sentencing
      verdicts. Those who favored the death penalty differed from those who had doubts
      about the penalty in gender, affiliation, fundamentalism, evangelism, literal
      Biblical interpretism, beliefs about God's attitudes toward murders, and
      perceptions of how their religious groups felt about the death penalty. These
      relationships generally held after mock jurors were death qualified. Gender,
      fundamentalism, literal interpretism, beliefs about God's death penalty position,
      and perceptions of how one's religious group felt about the death penalty
      predicted death penalty sentencing verdicts. Future research could determine
      whether using peremptory challenges to exclude potential jurors based on religion
      can help lawyers choose a more favorable jury.

PMID- 17546481
TI  - An indepth actuarial assessment for wife assault recidivism: the Domestic
      Violence Risk Appraisal Guide.
AB  - An actuarial tool, the Ontario Domestic Assault Risk Assessment (ODARA), predicts
      recidivism using only variables readily obtained by frontline police officers.
      Correctional settings permit more comprehensive assessments. In a subset of ODARA
      construction and cross-validation cases, 303 men with a police record for wife
      assault and a correctional system file, the VRAG, SARA, Danger Assessment, and
      DVSI also predicted recidivism, but the Hare Psychopathy Checklist (PCL-R) best
      improved prediction of recidivism, occurrence, frequency, severity, injury, and
      charges. In 346 new cases, ODARA and PCL-R independently predicted recidivism. An
      algorithm was derived for a combined instrument, the Domestic Violence Risk
      Appraisal Guide (DVRAG), and an experience table is presented (N=649). Results
      indicated the importance of antisociality in wife assault.

PMID- 17546482
TI  - Addressing gaps in the maturity of judgment literature: age differences and
      delinquency.
AB  - Over the past decade, a majority of states have legislated to expand their
      capacity to try adolescents as adults [Griffin (2003). Trying and sentencing
      juveniles as adults: An analysis of state transfer and blended sentencing laws.
      Pittsburgh, PA: National Center for Juvenile Justice]. In response, researchers
      have investigated factors that may affect adolescent culpability [Steinberg and
      Scott (Am Psychol 58(12):1009-1018, 2003)]. Research on immature judgment posits
      that psychosocial influences on adolescent decision processes results in reduced
      criminal responsibility [Cauffman and Steinberg (Behav Sci Law 18(6):741-760,
      2000); Scott, Reppucci, and Woolard (Law Hum Behav 19(3):221-244, 1995);
      Steinberg and Cauffman (Law Hum Behav 20(3):249-272, 1996)]. The current study
      utilizes hypothetical vignettes and standardized measures of maturity of judgment
      (responsibility, temperance, and perspective) to examine gaps in previous
      maturity of judgment findings (Cauffman and Steinberg 2000). This work suggests
      that adolescents (ages 14-17) display less responsibility and perspective
      relative to college students (ages 18-21), young-adults (ages 22-27), and adults
      (ages 28-40). Further, this research finds no maturity of judgment differences
      between delinquent and non-delinquent youth, but does find significant maturity
      of judgment differences between high and low delinquency male youth. Finally,
      results show that maturity of judgment predicts self-reported delinquency beyond
      the contributions of age, gender, race, education level, SES, and antisocial
      decision making. Implications for the juvenile justice system are discussed.

PMID- 17546483
TI  - Competence-related abilities and psychiatric symptoms: an analysis of the
      underlying structure and correlates of the MacCAT-CA and the BPRS.
AB  - The current study used confirmatory factor analysis to examine the factor
      structures of two instruments commonly used in the assessment of competency to
      stand trial--the MacArthur Competence Assessment Tool--Criminal Adjudication
      (MacCAT-CA) and the Brief Psychiatric Rating Scale (BPRS). Results revealed
      support for the three-subscale factor structure of the MacCAT-CA defined by the
      authors of the instrument; for a slightly altered three-factor structure defined
      by Zapf, Skeem, and Golding (2005, Psychological Assessment, 17, 433-445); and
      for the four symptom clusters of the BPRS as defined by Hedlund and Vieweg (1980,
      Journal of Operational Psychiatry, 11, 48-63). In addition, exploratory factor
      analysis of all 24 items of the BPRS revealed a five-factor structure.
      Correlations between psychiatric symptoms, symptom clusters, and competence
      related abilities were also examined using the previously identified and the
      newly identified factor structures of the MacCAT-CA and the BPRS. Significant
      relations between symptoms and psycholegal abilities are discussed.

PMID- 17546484
TI  - Characteristics and pregnancy outcomes of pregnant women asymptomatic for
      bacterial vaginosis.
AB  - STUDY DESIGN: To determine the clinical, behavioral or demographic factors
      associated with asymptomatic bacterial vaginosis (BV) and to examine if women
      with asymptomatic BV had a higher risk of a variety of pregnancy outcomes
      compared to symptomatic BV positive women. For this study, 1916 pregnant women
      who were 12 weeks' gestation or less were enrolled. Interviewers facilitated
      vaginal swab collection for BV assessment, and completed the baseline
      questionnaire. BV was identified by Gram stain. RESULTS: Forty percent of
      pregnant women screened positive for BV and a substantial proportion of BV
      positive pregnant women were asymptomatic (67%). Asymptomatic BV positive women
      reported lower stress scores (RR = 0.78, 95% CI: 0.67-0.89), slightly more prior
      STD's (RR = 1.03, 95% CI: 1.01-1.07), and a higher quantity of Mobiluncus (RR =
      1.04 95% CI: 1.01-1.07) compared to symptomatic BV positive women. We did not
      find an increase in adverse pregnancy outcomes related to BV symptomatology.
      CONCLUSION: Among first trimester pregnant women, only stress, STD history, and
      quantity of Mobiluncus were associated with symptom reports among BV positive
      pregnant women. We also found that women with asymptomatic BV did not have an
      increased risk of a variety of adverse pregnancy outcomes compared to symptomatic
      BV positive women.

PMID- 17546485
TI  - Transcriptional activity of genes encoding interferon gamma (IFNgamma) and its
      receptor assessed in peripheral blood mononuclear cells in patients with cardiac
      syndrome X.
AB  - BACKGROUND: Cardiac syndrome X is typically characterized by effort induced
      anginal pain with ST segment depression suggestive of myocardial ischemia and
      normal coronary arteries at angiography. The possible mechanism that may
      participate in the pathology of CSX is a microvascular dysfunction related to
      inflammatory process affecting endothelium. Interferon gamma (IFN-gamma) is an
      important cytokine in inflammatory reaction. It acts through its specific
      receptor composed of 2 subunits IFN-gamma R1 (ligand binding) and R2 (signal
      transduction). The expression and proportion of these subunits influences IFN
      gamma activity. The aim of the study was to assess the gene expression of IFN
      gamma and its receptors in peripheral blood mononuclear cells (PBMC) from
      patients with syndrome X. METHODS: The study was carried out in 36 patients aged
      44-77 (average 57 years old) with cardiac syndrome X and 23 sex- and age-matched
      healthy subjects (control group). To evaluate gene expression of IFNgamma and its
      receptor total mRNA was extracted from peripheral blood mononuclear cells (PBMC)
      and the number of mRNA copies were assessed by quantitive reverse transcriptase
      polymerase chain reaction (QRT-PCR). RESULTS: We have not observed statistically
      significant differences in INFgamma gene expression between studied group and
      control. Genes encoding IFNgamma receptor subunits showed higher expression in
      PBMCs from patients with cardiac syndrome X vs control subjects (IFNgammaR1,
      97,244 +/- 26,956 c/microg vs 12,120 +/- 2,940 c/microg, p < 0.005, respectively
      and IFNgammaR2, 129,153 +/- 36,883 c/microg vs 16,445 +/- 2,923 c/microg, p <
      0.005, respectively). CONCLUSION: Variation in transcriptional activity of genes
      encoding INF-gamma receptor subunits may affect function of microvasculature and
      thereby participate in the pathology of cardiac syndrome X.

PMID- 17546486
TI  - Azithromycin as a cause of QT-interval prolongation and torsade de pointes in the
      absence of other known precipitating factors.
AB  - During treatment with azithromycin, a 55 year-old woman developed a newly
      prolonged QT interval and torsade de pointes in the absence of known risk
      factors. Female gender and acute renal failure may be considerations in patients
      treated with azithromycin.

PMID- 17546488
TI  - Using time-delay to improve social play skills with peers for children with
      autism.
AB  - Interventions that teach social communication and play skills are crucial for the
      development of children with autism. The time delay procedure is effective in
      teaching language acquisition, social use of language, discrete behaviors, and
      chained activities to individuals with autism and developmental delays. In this
      study, three boys with autism, attending a non-public school, were taught play
      activities that combined a play sequence with requesting peer assistance, using a
      graduated time delay procedure. A multiple-baseline across subjects design
      demonstrated the success of this procedure to teach multiple-step social play
      sequences. Results indicated an additional gain of an increase in pretend play by
      one of the participants. Two also demonstrated a generalization of the skills
      learned through the time delay procedure.

PMID- 17546489
TI  - Estimating the burden of disease for autism spectrum disorders in Spain in 2003.
AB  - Autism Spectrum Disorders (ASD) are lifelong neurodevelopmental disabilities.
      Burden of Disease is an indicator that provides important information on health
      status and outcomes such as premature mortality and disability. In order to
      estimate the burden of disease of ASD in the Spanish population during 2003, we
      followed the procedures used in the WHO Global Burden of Disease Study. ASD
      generated 43,928 Disability Adjusted Life Years (DALY) in Spain in 2003, from
      which 33,797 were attributable to Autistic Disorder and 10,131 were caused by
      Asperger's Disorder and Pervasive Developmental Disorder-Not Otherwise Specified.
      DALY could be a useful tool for health policy makers for setting health service
      priorities, allocating available resources effectively and providing a comparable
      measure of output for early intervention.

PMID- 17546490
TI  - Enhancing the conversation skills of a boy with Asperger's Disorder through
      Social Stories and video modeling.
AB  - This study combined Social Stories with video modeling in an effort to enhance
      the conversation skills of a boy with Asperger's Disorder. Treatment consisted of
      two components: (a) observation of video taped Social Stories that included two
      adults modeling targeted conversational skills and (b) 5-min social interactions.
      A multiple baseline design across behaviors was used to evaluate the intervention
      and an increase in 2 out of 3 targeted conversation skills occurred. In addition,
      generalized behavior changes were observed. These findings provide support for
      including Social Stories as part of a video treatment package in teaching complex
      social interaction behaviors to young children with Asperger's Disorder.

PMID- 17546491
TI  - Constant and progressive time delay procedures for teaching children with autism:
      a literature review.
AB  - A review of 22 empirical studies examining the use of constant (CTD) and
      progressive (PTD) time delay procedures employed with children with autism frames
      an indirect analysis of the demographic, procedural, methodological, and outcome
      parameters of existing research. None of the previous manuscripts compared the
      two response prompting procedures. This review suggests that the effectiveness of
      the two procedures is similar on some variables. However, the CTD procedure
      resulted in more errors to criterion, a greater magnitude of procedural
      modifications, and in a delayed moment of transfer of stimulus control than in
      the PTD studies. Conclusions may influence clinical and educational practices and
      indicate a need for research.

PMID- 17546492
TI  - Role of a consensus AP-2 regulatory sequence within the Epstein-Barr virus LMP1
      promoter in EBNA2 mediated transactivation.
AB  - The Epstein-Barr virus (EBV) tumor-associated latent membrane protein 1 (LMP1)
      gene expression is transactivated by EBV nuclear antigen 2 (EBNA2) in human B
      cells. We previously reported that an E-box element at the LMP1 regulatory
      sequence (LRS) represses transcription of the LMP1 gene through the recruitment
      of a Max-Mad1-mSin3A complex. In the present study, using deletion/mutation
      analysis, and electrophoretic mobility shift assays, we show that the promoter
      region adjacent to the E-box (-59/-67) is required for the full repression
      conferred by E-box binding proteins. The repressive effect of these factors was
      overcome by an inhibitor of histone deacetylation, Trichostatin A (TSA),
      concurring with the reports that histone deacetylation plays an important role in
      repression mediated by Max-Mad1-mSin3A complex. Furthermore, ChIP analyses showed
      that histones at the transcriptionally active LMP1 promoter were hyperacetylated,
      whereas in the absence of transcription they were hypoacetylated. EBNA2
      activation of the promoter required a consensus AP-2 sequence in the -103/-95 LRS
      region. While EMSA results and the low level of AP-2 factors expression in B
      cells argue against known AP-2 factors binding to this site, several pieces of
      evidence point to a similar mechanism of promoter activation as seen by AP-2
      factors. We conclude that an AP-2 site-binding factor and EBNA2 act in concert to
      overcome the repression of the LMP1 promoter via the consensus AP-2 site. This
      activation showed strong correlation with histone hyperacetylation at the
      promoter, indicating this to be a major mechanism for the EBNA2 mediated LMP1
      transactivation.

PMID- 17546493
TI  - Characterisation and partial sequence analysis of two novel cypoviruses isolated
      from the winter moth Operophtera brumata (Lepidoptera: Geometridae).
AB  - The complete nucleotide sequences of genomic segments S5 to S10 from Operophtera
      brumata cypovirus 18 (OpbuCPV18), and the complete nucleotide sequences of
      genomic segments S2, S5, S9 and S10 from Operophtera brumata cypovirus 19
      (OpbuCPV19) have been determined. Each genome segment contained a single open
      reading frame (ORF). Conserved motifs 5' (AGUAAA....GUUAGCU) 3' were found at the
      ends of each segment of OpbuCPV18, whilst conserved motifs 5' (AACAAA....UUUGC)
      3' were found at each segment terminus of OpbuCPV19. The putative proteins were
      compared with those of other members of the Reoviridae family. Phylogenetic
      analysis using the polyhedrin gene (S10) indicated that OpbuCPV18 was most
      closely related to Dendrolimus punctatus cypovirus 1, whilst OpbuCPV19 was most
      closely related to Trichoplusia ni cypovirus 15. In addition, analysis of S2,
      which encoded a putative RNA-dependant RNA polymerase gene, confirmed OpbuCPV19
      belonged to the genus Cypovirus. Following the expression of the ORF from
      OpbuCPV19 S10, using a baculovirus expression vector, occlusion bodies were
      observed in insect cell culture. This demonstrated that segment 10 coded for the
      polyhedrin gene, capable of forming a polyhedral crystalline matrix.

PMID- 17546495
TI  - Evolution of the special projects of national significance prevention with HIV
      infected persons seen in primary care settings initiative.

PMID- 17546494
TI  - Induction of chromosomally integrated HIV-1 LTR requires RBF-2 (USF/TFII-I) and
      Ras/MAPK signaling.
AB  - The HIV-1 LTR is regulated by multiple signaling pathways responsive to T cell
      activation. In this study, we have examined the contribution of the MAPK,
      calcineurin-NFAT and TNFalpha-NF-kappaB pathways on induction of chromosomally
      integrated HIV-1 LTR reporter genes. We find that induction by T-cell receptor
      (CD3) cross-linking and PMA is completely dependent upon a binding site for RBF-2
      (USF1/2-TFII-I), known as RBEIII at -120. The MAPK pathway is essential for
      induction of the wild type LTR by these treatments, as the MEK inhibitors PD98059
      and U0126 block induction by both PMA treatment and CD3 cross-linking.
      Stimulation of cells with ionomycin on its own has no effect on the integrated
      LTR, indicating that calcineurin-NFAT is incapable of causing induction in the
      absence of additional signals, but stimulation with both PMA and ionomycin
      produces a synergistic response. In contrast, stimulation of NF-kappaB by
      treatment with TNFalpha causes induction of both the wild type and RBEIII mutant
      LTRs, an effect that is independent of MAPK signaling. USF1, USF2 and TFII-I from
      unstimulated cells are capable of binding RBEIII in vitro, and furthermore can be
      observed on the LTR in vivo by chromatin imunoprecipitation from untreated cells.
      DNA binding activity of USF1/2 is marginally stimulated by PMA/ ionomycin
      treatment, and all three factors appear to remain associated with the LTR
      throughout the course of induction. These results implicate major roles for the
      MAPK pathway and RBF-2 (USF1/2-TFII-I) in coordinating events necessary for
      transition of latent integrated HIV-1 to active transcription in response to T
      cell signaling.

PMID- 17546496
TI  - Access to housing as a structural intervention for homeless and unstably housed
      people living with HIV: rationale, methods, and implementation of the housing and
      health study.
AB  - Homelessness and unstable housing have been associated with HIV risk behavior and
      poorer health among persons living with HIV/AIDS (PLWHA), yet prior research has
      not tested causal associations. This paper describes the challenges, methods, and
      baseline sample of the Housing and Health Study, a longitudinal, multi-site,
      randomized controlled trial investigating the effects of providing immediate
      rental housing assistance to PLWHA who were homeless or at severe risk of
      homelessness. Primary outcomes included HIV disease progression, medical care
      access and utilization, treatment adherence, mental and physical health, and
      risks of transmitting HIV. Across three study sites, 630 participants completed
      baseline sessions and were randomized to receive either immediate rental housing
      assistance (treatment group) or assistance finding housing according to local
      standard practice (comparison group). Baseline sessions included a questionnaire,
      a two-session HIV risk-reduction counseling intervention, and blood sample
      collection to measure CD4 counts and viral load levels. Three follow-up visits
      occurred at 6, 12, and 18 months after baseline. Participants were mostly male,
      Black, unmarried, low-income, and nearly half were between 40 and 49 years old.
      At 18 months, 84% of the baseline sample was retained. The retention rates
      demonstrate the feasibility of conducting scientifically rigorous housing
      research, and the baseline results provide important information regarding
      characteristics of this understudied population that can inform future HIV
      prevention and treatment efforts.

PMID- 17546497
TI  - Differential effect of hormone therapy on E1S-sulfatase activity in non-malignant
      and cancerous breast cells in vitro.
AB  - Breast tissue possesses the enzymes for local estrogen biosynthesis. We measured
      the effect of Estradiol (E2), Tibolone (OrgOD14) and its metabolite Org4094 on
      estrone sulfate (E1S)-sulfatase (STS) using breast cancer (MCF-7) and non
      malignant breast cells (HBL-100). Cells were cultured in 5% steroid depleted
      fetal calf serum for 3 days and subsequently incubated with each steroid for
      either 24 h or directly in cell extracts. STS mRNA and protein expression, and
      its subcellular localization were determined by semi-quantitative RT-PCR,
      immunoblotting, and confocal immunofluorescence microscopy. STS activity was
      evaluated by incubating homogenized breast cells with [(3)H]-E1S. The products E1
      and E2 were separated by thin layer chromatography. STS was co-localized with the
      Golgi marker protein GM130 and the endoplasmic reticulum marker protein calnexin.
      Treatment did not significantly alter STS mRNA expression. STS protein expression
      was increased by each steroid in HBL-100 cells but by E2 only in MCF-7 cells. 24
      h incubation with OrgOD14 and Org4094 did not alter STS activity in both cell
      lines. However, STS activity was significantly diminished in HBL-100 but slightly
      increased in MCF-7 cells by 24 h treatment with E2. "Direct" incubation of cell
      extracts, eliminating cellular regulation of metabolism, reduced estrogen
      biosynthesis regardless of cell line and treatment. In conclusion, the immediate
      reduction of estrogen biosynthesis by OrgOD14 is counteracted by an increased STS
      protein expression. On the contrary, E2 exerts a differential effect on STS in
      HBL-100 and MCF-7 cells. The transition from normal to malignant breast cells may
      be accompanied by an abolished autoregulation of local estrogen formation.

PMID- 17546498
TI  - Estimation of parameters in logistic and log-logistic distribution with grouped
      data.
AB  - In many situations, instead of a complete sample, data are available only in
      grouped form. For example, grouped failure time data occur in studies in which
      subjects are monitored periodically to determine whether failure has occurred in
      the predetermined intervals. Here the model under consideration is the log
      logistic distribution. This paper demonstrates the existence and uniqueness of
      the MLEs of the parameters of the logistic distribution under mild conditions
      with grouped data. The times with the maximum failure rate and the mode of the
      p.d.f. of the log-logistic distribution are also estimated based on the MLEs. The
      methodology is further studied with simulations and exemplified with a data set
      with artificially introduced grouping from a locomotive life test study.

PMID- 17546499
TI  - The neuropsychology and neurology of sexual deviance: a review and pilot study.
AB  - Current neurological hypotheses of paraphilia posit that sexual deviance is
      associated with frontal and/or temporal lobe damage. This broad conception is
      based on few investigations, however, and the first goal of this study was to
      review the existing data derived from neuropsychiatry, neuroimaging and
      neuropsychology. It is concluded that although fronto-temporal dysfunctions are
      sporadically reported among sexual offenders, the evidence is scarce and it might
      not be specific to this type of offending. The second objective of this
      investigation was to gather preliminary neuropsychological data with more
      homogeneous subgroups of sexual offenders. A profile of lower-order executive
      dysfunctions (e.g. sustained attention and inhibition) and verbal deficits with
      intact or good capacities for higher-order executive functioning (e.g. reasoning
      and cognitive flexibility) and visuo-spatial processing was preferentially found
      among sexual offenders, suggesting basal fronto-temporal anomalies. Importantly,
      pedophiles were more consistently and severely impaired than rapists of adults.
      However, this basal fronto-temporal profile is not characteristic of sexual
      deviance, as it is also found in association with delinquency and criminality in
      general. Future neuropsychological and brain imaging studies should consider
      subgroups of sexual offenders and recruit non-sexual violent persons and non
      violent individuals in order to disentangle the complex relations between brain
      anomalies and sexual deviance.

PMID- 17546500
TI  - The impact of nativity on chronic diseases, self-rated health and comorbidity
      status of Asian and Hispanic immigrants.
AB  - This study examines the physical health status of immigrants with specific
      considerations of Asian and Hispanic populations and explores possible mechanisms
      through which health outcomes of interest can be explained. Analyses of the
      National Health Interview Surveys (NHIS) of 2000 and 2001 revealed that foreign
      born individuals reported fewer chronic diseases (hypertension, heart disease,
      asthma, cancer and diabetes) and had lower prevalences of various chronic
      diseases compared with U.S.-born whites, controlling for possible confounders and
      mediators. However, U.S-born minority groups did not show the health advantage
      seen in foreign-born immigrants, reflecting the importance of nativity
      distinctions in studying immigrant health. Despite having fewer chronic diseases,
      foreign-born Asians were more likely to rate their health negatively relative to
      their U.S.-born counterparts and to U.S.-born whites. In addition, our findings
      provide evidence that failure to consider comorbid status may attenuate the
      nativity effect on certain chronic diseases.

PMID- 17546501
TI  - Reproductive characteristics of Southeast Asian immigrants before and after
      migration.
AB  - We describe the reproductive health and practices of Hmong immigrants before and
      after migration to the United States. Data were gathered as part of an ongoing
      study on the impact of perinatal exposure to environmental chemicals on
      children's health in Hmong residents of Green Bay, Wisconsin between August 1999
      and May 2002. Of the 742 pregnancies reported by 141 reproductive-aged couples,
      669 were live births. The Hmong have an average of 5.2 children (range 0-14) and
      the sex ratio differed by country of birth. Prenatal care began in the first
      trimester for 60% of US-born infants, up from 12% prior to immigration.
      Breastfeeding decreased from 94% and 88% in Laos and Thailand to only 11% for
      Hmong born in the US. Contraceptive use was reported by 25.5% of women; few
      reported smoking and alcohol consumption. The results suggest that Hmong
      immigrants may benefit from public health support targeting prenatal care and
      breastfeeding practices.

PMID- 17546502
TI  - Hmong adults self-rated oral health: a pilot study.
AB  - Since 1975, the Hmong refugee population in the U.S. has increased over 200%.
      However, little is known about their dental needs or self-rated oral health
      (SROH). The study aims were to: (1) describe the SROH, self-rated general health
      (SRGH), and use of dental/physician services; and (2) identify the factors
      associated with SROH among Hmong adults. A cross-sectional study design with
      locating sampling methodology was used. Oral health questionnaire was
      administered to assess SROH and SRGH, past dental and physician visits, and
      language preference. One hundred twenty adults aged 18-50+ were recruited and 118
      had useable information. Of these, 49% rated their oral health as poor/fair and
      30% rated their general health as poor/fair. Thirty-nine percent reported that
      they did not have a regular source of dental care, 46% rated their access to
      dental care as poor/fair, 43% visited a dentist and 66% visited a physician
      within the past 12 months. Bivariate analyses demonstrated that access to dental
      care, past dental visits, age and SRGH were significantly associated with SROH (P
      < 0.05). Multivariate analyses demonstrated a strong association between access
      to dental care and good/excellent SROH. About half of Hmong adults rated their
      oral health and access to dental care as poor. Dental insurance, access to dental
      care, past preventive dental/physician visits and SRGH were associated with SROH.

PMID- 17546503
TI  - Non-invasive time-lapsed monitoring and quantification of engineered bone-like
      tissue.
AB  - The formation of bone-like tissue from human mesenchymal stem cells (hMSC)
      cultured in osteogenic medium on silk fibroin scaffolds was monitored and
      quantified over 44 days in culture using non-invasive time-lapsed micro-computed
      tomography (microCT). Each construct was imaged nine times in situ. From microCT
      imaging, detailed morphometrical data on bone volume density, surface-to-volume
      ratio, trabecular thickness, trabecular spacing, and the structure model index
      and tissue mineral density were obtained. microCT irradiation did not impact the
      osteogenic performance of hMSCs based on DNA content, alkaline phosphatase
      activity, and calcium deposition when compared to non-exposed control samples.
      Bone-like tissue formation initiated at day 10 of the culture with the deposition
      of small mineralized clusters. Tissue mineral density increased linearly over
      time. The surface-to-volume ratio of the bone-like tissues converged
      asymptotically to 26 mm(-1). Although in vitro formation of bone-like tissue
      started from clusters, the overall bone volume was not predictable from the time,
      number, and size of initially formed bone-like clusters. Based on microstructural
      analysis, the morphometry of the tissue-engineered constructs was found to be in
      the range of human trabecular bone. In future studies, non-invasive, time-lapsed
      monitoring may enable researchers to culture tissues in vitro, right until the
      development of a desired morphology is accomplished. Our data demonstrate the
      feasibility of qualitatively and quantitatively detailing the spatial and
      temporal mineralization of bone-like tissue formation in tissue engineering.

PMID- 17546504
TI  - Probabilistic modeling of knee muscle moment arms: effects of methods, origin
      insertion, and kinematic variability.
AB  - In musculoskeletal modeling, reliable estimates of muscle moment arms are an
      important step in accurately predicting muscle forces and joint moments. The
      degree of agreement between the two common methods of calculating moment arms
      tendon excursion (TE) and geometric origin-insertion, is currently unknown for
      the muscles crossing the knee joint. Further, measured moment arm data are
      subject to variability in estimation of attachment sites as points from irregular
      surfaces on the bones, and due to differences in joint kinematics observed in
      vivo. Thus, the objectives of the present study were to compare moment arms of
      major muscles crossing the knee joint obtained from TE and geometric methods
      using a finite element-based lower extremity model, and to quantify the effects
      of potential muscle origin-insertion and tibiofemoral kinematic variability on
      the predicted moment arms using probabilistic methods. A semiconstrained, fixed
      bearing, posterior cruciate-retaining total knee arthroplasty was included due to
      available in vivo kinematic data. In this study, muscle origin and insertion
      locations and kinematic variables were represented as normal distributions with
      standard deviations of 5 mm for origin-insertion locations and up to 1.6 mm and
      3.0 degrees for the kinematic parameters. Agreement between the deterministic
      moment arm calculations from the two methods was excellent for the flexors, while
      differences in trends and magnitudes were observed for the extensor muscles.
      Model-predicted deterministic moment arms from both methods agreed reasonably
      with the experimental values from available literature. The uncertainty in input
      parameters resulted in substantial variability in predicted moment arms, with the
      size of 1-99% confidence interval being up to 41.3 and 35.8 mm for the TE and
      geometric methods, respectively. The sizeable range of moment arm predictions and
      associated excursions has the potential to affect a muscle's operating range on
      the force-length curve, thus affecting joint moments. In this study, moment arm
      predictions were more dependent on muscle origin-insertion locations than the
      kinematic variables. The important parameters from the TE method were the origin
      and insertion locations in the sagittal plane, while the insertion location in
      the sagittal plane was the dominant parameter using the geometric method.

PMID- 17546505
TI  - How green is my city?

PMID- 17546506
TI  - A polymorphism of microRNA 27a genome region is associated with the development
      of gastric mucosal atrophy in Japanese male subjects.
AB  - Noncoding microRNAs regulate the expression of various mRNAs. We attempted to
      clarify the relationship between miR-27a genome polymorphism and chronic
      gastritis. The study was performed in 179 patients with no evidence of gastric
      malignancy. The severity of histologic chronic gastritis was classified according
      to the updated Sydney system. The frequency of miR-27a G allele was 34.6%.
      Although the frequencies of miR-27a G allele were increased in subjects with
      peptic ulcer or severe mucosal atrophy, no significant differences were seen. The
      miR-27a polymorphism showed an interaction with gender in relation to gastric
      mucosal atrophy (P=.090). In only male subjects, the miR-27a polymorphism was
      associated with the gastric mucosal atrophy (P=.039) and both atrophy and
      metaplasia scores in G/G group were significantly higher than those in the other
      groups. The miR-27a genome region polymorphism may be an important definitive
      factor to develop the gastric mucosal atrophy in Japanese male subjects.

PMID- 17546507
TI  - Effect of imatinib mesylate in a patient with a metastatic gastrointestinal
      stromal tumor with a c-kit mutation in exon 11.

PMID- 17546508
TI  - Reduced Kv1.3 potassium channel expression in human prostate cancer.
AB  - The presence of Kv1.3 voltage-gated potassium channels in rat and human prostate
      epithelial cells has been previously reported. We examined, by
      immunohistochemistry, Kv1.3 levels in 10 normal human prostate, 18 benign
      prostatic hyperplasia (BPH) and 147 primary human prostate cancer (Pca)
      specimens. We found high epithelial expression of Kv1.3 in all normal prostate,
      16 BPH and 77 (52%) Pca specimens. Compared to normal, Kv1.3 levels were reduced
      in 1 (6%) BPH specimen and in 70 (48%) Pca specimens. We found a significant
      inverse correlation between Kv1.3 levels and tumor grade (r = -0.25, P = 0.003)
      as well as tumor stage (r = -0.27, P = 0.001). Study of an additional 30 primary
      Pca specimens showed that 15 (50%) had reduced Kv1.3 immunostaining compared to
      matched normal prostate tissue. Our data suggest that in Pca reduced Kv1.3
      expression occurs frequently and may be associated with a poor outcome.

PMID- 17546509
TI  - Interplay between cystic fibrosis transmembrane regulator and gap junction
      channels made of connexins 45, 40, 32 and 50 expressed in oocytes.
AB  - The cystic fibrosis transmembrane regulator (CFTR) is a Cl(-) channel known to
      influence other channels, including connexin (Cx) channels. To study the
      functional interaction between CFTR and gap junction channels, we coexpressed in
      Xenopus oocytes CFTR and either Cx45, Cx40, Cx32 or Cx50 and monitored junctional
      conductance (G (j)) and its sensitivity to transjunctional voltage (V (j)) by the
      dual voltage-clamp method. Application of forskolin induced a Cl(-) current;
      increased G (j) approximately 750%, 560%, 64% and 8% in Cx45, Cx40, Cx32 and
      Cx50, respectively; and decreased sensitivity to V (j ) gating, monitored by a
      change in the ratio between G (j) steady state and G (j) peak (G (j)SS/G (j)PK)
      at the pulse. In oocyte pairs expressing just Cx45 in one oocyte (#1) and both
      Cx45 and CFTR in the other (#2), with negative pulses applied to oocyte #1
      forskolin application still increased G (j) and decreased the sensitivity to V
      (j) gating, indicating that CFTR activation is effective even when it affects
      only one of the two hemichannels and that the G (j) and V (j) changes are not
      artifacts of decreased membrane resistance in the pulsed oocyte. COOH-terminus
      truncation reduced the forskolin effect on Cx40 (Cx40TR) but not on Cx32 (Cx32TR)
      channels. The data suggest a cross-talk between CFTR and a variety of gap
      junction channels. Cytoskeletal scaffolding proteins and/or other intermediate
      cytoplasmic proteins are likely to play a role in CFTR-Cx interaction.

PMID- 17546510
TI  - Protein secretion and membrane insertion systems in gram-negative bacteria.
AB  - In contrast to other organisms, gram-negative bacteria have evolved numerous
      systems for protein export. Eight types are known that mediate export across or
      insertion into the cytoplasmic membrane, while eight specifically mediate export
      across or insertion into the outer membrane. Three of the former secretory
      pathway (SP) systems, type I SP (ISP, ABC), IIISP (Fla/Path) and IVSP (Conj/Vir),
      can export proteins across both membranes in a single energy-coupled step. A
      fourth generalized mechanism for exporting proteins across the two-membrane
      envelope in two distinct steps (which we here refer to as type II secretory
      pathways [IISP]) utilizes either the general secretory pathway (GSP or Sec) or
      the twin-arginine targeting translocase for translocation across the inner
      membrane, and either the main terminal branch or one of several protein-specific
      export systems for translocation across the outer membrane. We here survey the
      various well-characterized protein translocation systems found in living
      organisms and then focus on the systems present in gram-negative bacteria.
      Comparisons between these systems suggest specific biogenic, mechanistic and
      evolutionary similarities as well as major differences.

PMID- 17546511
TI  - Swelling-activated K+ efflux and regulatory volume decrease efficiency in human
      bronchial epithelial cells.
AB  - This study describes the correlation between cell swelling-induced K+ efflux and
      volume regulation efficiency evaluated with agents known to modulate ion channel
      activity and/or intracellular signaling processes in a human bronchial epithelial
      cell line, 16HBE14o(-1). Cells on permeable filter supports, differentiated into
      polarized monolayers, were monitored continuously at room temperature for changes
      in cell height (T(c)), as an index of cell volume, whereas (86)Rb efflux was
      assessed for K+ channel activity. The sudden reduction in osmolality of both the
      apical and basolateral perfusates (from 290 to 170 mosmol/kg H(2)O) evoked a
      rapid increase in cell volume by 35%. Subsequently, the regulatory volume
      decrease (RVD) restored cell volume almost completely (to 94% of the isosmotic
      value). The basolateral (86)Rb efflux markedly increased during the hyposmotic
      shock, from 0.50 +/- 0.03 min(-1) to a peak value of 6.32 +/- 0.07 min(-1), while
      apical (86)Rb efflux was negligible. Channel blockers, such as GdCl(3) (0.5 mM),
      quinine (0.5 mM) and 5-nitro-2-(3-phenyl-propylamino) benzoic acid (NPPB, 100
      microM), abolished the RVD. The protein tyrosine kinase inhibitors tyrphostin 23
      (100 microM) and genistein (150 microM) attenuated the RVD. All agents decreased
      variably the hyposmosis-induced elevation in (86)Rb efflux, whereas NPPB induced
      a complete block, suggesting a link between basolateral K(+) and Cl(-1) efflux.
      Forskolin-mediated activation of adenylyl cyclase stimulated the RVD with a
      concomitant increase in basolateral (86)Rb efflux. These data suggest that the
      basolateral extrusion of K+ and Cl(-1) from 16HBE14o(-1) cells in response to
      cell swelling determines RVD efficiency.

PMID- 17546512
TI  - The association between angiotensin II-induced free radical generation and
      membrane fluidity in neutrophils of patients with metabolic syndrome.
AB  - Angiotensin II (Ang II) is able to induce free radical generation in neutrophils,
      which is more elevated in neutrophils of patients with hypercholesterolemia (HC).
      In addition, the signal processing through angiotensin I (Ang I) receptors is
      altered. In present study, we compared the Ang II-triggered free radical
      generation of neutrophils obtained from patients with relatively isolated forms
      of metabolic syndrome (MS) with membrane-bound cholesterol content and membrane
      fluidity. We determined the enhancement of Ang II-induced superoxide anion and
      leukotriene C(4) (LTC(4)) generation, membrane fluidity and cell-bound
      cholesterol content of neutrophils obtained from 12 control subjects, 11 patients
      with obesity (Ob), 10 patients with type 2 diabetes mellitus (t2-DM) and 12
      patients with HC. The alteration of signal processing was studied after
      preincubation with different inhibiting drugs. Superoxide anion, LTC(4)
      production and membrane rigidity were increased in the following order: control <
      Ob < t2-DM < HC. Both Ang II-induced superoxide anion and LTC(4) generation were
      decreased in control cells by pertussis toxin and fluvastatin (Flu), whereas in
      each patient group, mepacrin, verapamil and Flu were effective, suggesting
      alterations in signal pathways, which may be attributed to isoprenylation. The
      enhancement of superoxide anion and LTC(4) generation correlated significantly
      with membrane rigidity, independently from the experimental groups and membrane
      bound cholesterol content. Membrane rigidity of neutrophils, obtained from
      patients with MS, plays a role in Ang II-induced free radical generation
      independent of intracellular cholesterol homeostasis.

PMID- 17546513
TI  - Effects of SR141716 and WIN 55,212-2 on tolerance to ethanol in rats using the
      acute and rapid procedures.
AB  - RATIONALE: Our previous findings have shown rapid cross-tolerance between ethanol
      and Delta(9)-tetrahydrocannabinol and that intraperitoneal (i.p.) injection of
      cannabinoid receptor type 1 (CB1R) antagonist SR141716 (SR) does not interfere
      with tolerance to either of these drugs in mice. OBJECTIVES: This study
      investigates the effects of SR, alone or in combination with the CB receptor
      agonist WIN 55,212-2 (WIN), on the development of acute and rapid tolerance to
      the incoordinating effect of ethanol in rats. MATERIALS AND METHODS: Male Wistar
      rats received SR, through i.p. (0.5-2.0 mg/kg) or intracerebroventricular
      (i.c.v.) injections (0.5-4.0 microg), alone or together with WIN (1.0 microg,
      i.c.v.), in combination with ethanol (2.7 g/kg, i.p.). Another group received WIN
      (1.0 microg, i.c.v.) in combination with ethanol (2.3 g/kg), and the rats were
      tested for motor coordination. Rapid tolerance was assessed 24 h later by
      administering ethanol to all animals and retesting them under the same dose
      regimen. Acute tolerance was evaluated for 75 min after ethanol (3.0 g/kg, i.p.)
      in animals treated with SR or WIN (i.c.v.). RESULTS: The reduced motor impairment
      on day 2 (i.e., rapid tolerance) was blocked by SR (i.p. and i.c.v.). WIN (1.0
      microg, i.c.v.) facilitated rapid tolerance and also prevented the blockade of
      rapid tolerance by SR (1.0 microg, i.c.v.). In the acute tolerance procedure, SR
      did not affect the motor incoordination induced by ethanol. CONCLUSIONS: The
      results suggest that the endocannabinoid system may contribute to the development
      of rapid tolerance to ethanol.

PMID- 17546519
TI  - Impact of ectomycorrhizosphere on the functional diversity of soil bacterial and
      fungal communities from a forest stand in relation to nutrient mobilization
      processes.
AB  - The ectomycorrhizal symbiosis alters the physicochemical and biological
      conditions in the surrounding soil, thus creating a particular environment called
      ectomycorrhizosphere, which selects microbial communities suspected to play a
      role in gross production and nutrient cycling. To assess the ectomycorrhizosphere
      effect on the structure of microbial communities potentially involved in the
      mobilization of nutrients from the soil minerals in a poor-nutrient environment,
      we compared the functional diversity of soil and ectomycorrhizosphere bacterial
      communities in a forest stand. Two hundred and sixty-four bacterial strains and
      107 fungal strains were isolated from the bulk soil of an oak (Quercus petraea)
      stand and from oak-Scleroderma citrinum ectomycorrhizosphere and ectomycorrhizae,
      in two soil organo-mineral horizons (0 to 3 cm and 5 to 10 cm). They were
      characterized using two in vitro tests related to their capacities to mobilize
      iron and phosphorus. We demonstrated that the oak-S. citrinum
      ectomycorrhizosphere significantly structures the culturable bacterial
      communities in the two soil horizons by selecting very efficient strains for
      phosphorus and iron mobilization. This effect was also observed on the diversity
      of the phosphate-solubilizing fungal communities in the lower soil horizon. A
      previous study already demonstrated that Laccaria bicolor-Douglas fir
      ectomycorrhizosphere structures the functional diversity of Pseudomonas
      fluorescens population in a forest nursery soil. Comparing to it, our work
      highlights the consistency of the mycorrhizosphere effect on the functional
      diversity of bacterial and fungal communities in relation to the mineral
      weathering process, no matter the fungal symbiont, the age and species of the
      host tree, or the environment (nursery vs forest). We also demonstrated that the
      intensity of phosphorus and iron mobilization by the ectomycorrhizosphere
      bacteria isolated from the lower soil horizon was significantly higher compared
      to that which was isolated from the upper horizon. This reveals for the first
      time a stratification of the functional diversity of the culturable soil
      bacterial communities as related to phosphorus and iron mobilization.

PMID- 17546520
TI  - Just add water and the Colorado River still reaches the sea.
AB  - A recent article in Environmental Management by All argued that flood flows in
      North America's Colorado River do not reach the Gulf of California because they
      are captured and evaporated in Laguna Salada, a below sea-level lakebed near the
      mouth of the river. We refute this hypothesis by showing that (1) due to its
      limited area, the Laguna Salada could have evaporated less than 10% of the flood
      flows that have occurred since 1989; (2) low flow volumes preferentially flow to
      the Gulf rather than Laguna Salada; (3) All's method for detecting water surface
      area in the Laguna Salada appears to be flawed because Landsat Thematic Mapper
      images of the lakebed show it to be dry when All's analyses said it was flooded;
      (4) direct measurements of salinity at the mouth of the river and in the Upper
      Gulf of California during flood flows in 1993 and 1998 confirm that flood waters
      reach the sea; and (5) stable oxygen isotope signatures in clam shells and fish
      otoliths recorded the dilution of seawater with fresh water during the 1993 and
      1998 flows. Furthermore, All's conclusion that freshwater flows do not benefit
      the ecology of the marine zone is incorrect because the peer-reviewed literature
      shows that postlarval larval shrimp populations increase during floods, and the
      subsequent year's shrimp harvest increases. Furthermore, freshwater flows
      increase the nursery area for Gulf corvina (Cynoscion othonopterus), an important
      commercial fish that requires estuarine habitats with salinities in the range of
      26-38 per thousand during its natal stages. Although flood flows are now much
      diminished compared to the pre-dam era, they are still important to the remnant
      wetland and riparian habitats of the Colorado River delta and to organisms in the
      intertidal and marine zone. Only a small fraction of the flood flows are
      evaporated in Laguna Salada.

PMID- 17546521
TI  - Past on-site experience, crowding perceptions, and use displacement of visitor
      groups to a peri-urban national park.
AB  - Past on-site experience was linked to the crowding perceptions and use
      displacement of 383 on-site visitors to the peri-urban Danube Floodplains
      National Park, Austria. Three visitor groups were determined according to their
      area experience: local residents from Vienna and rural communities, having the
      highest level of experience; regional visitors from the city and eastern Austria;
      and tourists from Austria and abroad with the lowest degree of experience.
      Crowding perceptions were significantly different across the user groups. More
      than 50% of local residents perceived the national park as crowded, whereas only
      27% of regional visitors and 19% of tourists reported such an evaluation. Even
      among local residents and regional visitors, respondents with more on-site
      experience expressed a greater impression of a crowded park. Differences in
      crowding evaluations between local rural and urban residents and between regional
      rural and urban visitors were not found. For 27% of local residents and 15% of
      regional visitors, use levels were so unacceptable that they displaced temporally
      and spatially, whereas use displacement was relatively irrelevant for tourists.
      The use displacement strategies involved differ among the three user groups.
      Management implications were discussed, taking the specific situation of the
      small national park on the urban-rural fringe into consideration.

PMID- 17546522
TI  - Understanding anglers' preferences for fishing tournament characteristics and
      policies.
AB  - Saltwater fishing tournaments in the United States are generally not regulated
      nor are there different fishing regulations for tournament and nontournament
      anglers. Although much is known about those who participate in fishing
      tournaments in terms of their fishing motivations, attitudes, and
      characteristics, much less is known at the angler population level regarding
      their preferences for tournament opportunities. Using a stated preference choice
      model with hypothetical scenarios to simulate participation choices and
      understand preferences, study objectives were to identify angler preferences for
      various types of tournament fishing "products." Four tournament policy
      characteristics were investigated: promotion of catch and release, bait
      restrictions, whether a percentage of the tournament entrance fee should go to
      support fishery management activities, and whether a tournament should be a
      nonprofit or profit-making venture. Three expectation attributes were inserted:
      tournament size, trip cost per day, and whether a tournament is family friendly.
      We sent seven different versions of the mail questionnaire to 1,633 anglers. Of
      795 returns, 648 were used for estimating conditional logit models. Analysis
      indicated that a scenario with no management interventions was not most
      preferred. Anglers most preferred a conservation-oriented option that introduced
      additional management measures. Overall, scenarios with management interventions
      were more favored than the status quo situation (with no management
      interventions). Although respondents showed reluctance to adopt other management
      related options, results generally indicated they were increasingly concerned
      with sustainability of fish stocks and potential conflicts between tournament and
      nontournament users and preferred tournament products that reflect these
      concerns.

PMID- 17546523
TI  - Using GIS to generate spatially balanced random survey designs for natural
      resource applications.
AB  - Sampling of a population is frequently required to understand trends and patterns
      in natural resource management because financial and time constraints preclude a
      complete census. A rigorous probability-based survey design specifies where to
      sample so that inferences from the sample apply to the entire population.
      Probability survey designs should be used in natural resource and environmental
      management situations because they provide the mathematical foundation for
      statistical inference. Development of long-term monitoring designs demand survey
      designs that achieve statistical rigor and are efficient but remain flexible to
      inevitable logistical or practical constraints during field data collection. Here
      we describe an approach to probability-based survey design, called the Reversed
      Randomized Quadrant-Recursive Raster, based on the concept of spatially balanced
      sampling and implemented in a geographic information system. This provides
      environmental managers a practical tool to generate flexible and efficient survey
      designs for natural resource applications. Factors commonly used to modify
      sampling intensity, such as categories, gradients, or accessibility, can be
      readily incorporated into the spatially balanced sample design.

PMID- 17546524
TI  - Status of heavy metals in agricultural soils as affected by different patterns of
      land use.
AB  - This study was conducted to determine status of heavy metals in agricultural
      soils under different patterns of land use. A total of 38, 40 and 45 soil samples
      for bare vegetable field, greenhouse vegetable field, and grain crop field were
      respectively taken from surface layer (0-20 cm) from selected experimental areas
      away from suburbs of ten counties (or districts or cities) in four provinces or
      municipalities of Huabei plain in north China. Information of crop production
      history, including varieties, rotation systems and fertilizer use, at the
      corresponding sampling sites was surveyed. Soil total Cu, Zn, Cd, Pb, Cr, As and
      Hg were measured. The results showed that the contents of total Cu, Zn, Cd, Pb,
      Cr, As, and Hg in the soil samples, especially soil total Cu and Zn contents,
      were higher in the bare vegetable field and the greenhouse vegetable field than
      that in the grain crop field. Long-term use of excessive chemical fertilizers and
      organic manures in the bare vegetable field and the greenhouse vegetable field
      contributed to the accumulation of Cu, Zn, and other heavy metals in the soils.
      The contents of total Cu, Zn, and other heavy metals in soils increased with
      increasing vegetable production history of the research areas. In comparison with
      the grain crop field, the comprehensive pollution indices of the seven soil heavy
      metals and the single-factor pollution indices of soil Zn, Cu, Cd, Cr, and Hg
      based on the second criterion of Environmental Quality Standard for Soils were
      significantly higher in the bare vegetable field and the greenhouse vegetable
      field. Soils from the greenhouse vegetable field were slightly contaminated
      according to the comprehensive pollution index, and soils from the bare vegetable
      field and the grain crop field were at the warning heavy metal pollution level.
      The soils were contaminated with Cd according to the single-factor pollution
      index. The Cd pollution was relatively more serious in the bare vegetable field
      and the greenhouse vegetable field than that in the grain crop field. The soils
      selected with different land use patterns were not contaminated with Zn, Cu, Pb,
      Cr, As and Hg.

PMID- 17546527
TI  - Postconditioning protects human atrial muscle through the activation of the RISK
      pathway.
AB  - Ischemic postconditioning (IPost) has been demonstrated to reduce myocardial
      injury in patients undergoing primary coronary angioplasty for an acute
      myocardial infarction.Pre-clinical animal studies suggest that pro-survival
      protein kinases of the Reperfusion Injury Salvage Kinase (RISK) pathway such as
      Akt and Erk1/2 mediate the cardioprotective effect of IPost. Whether IPost can
      protect human myocardial tissue ex vivo and whether it recruits the RISK pathway
      in human myocardium are both not known. To investigate this, atrial appendages
      were harvested from patients undergoing cardiac surgery. From these samples
      atrial trabeculae were isolated and mounted on a superperfusion apparatus and
      subjected to 90 min of hypoxia followed by 120 min of reoxygenation at the end of
      which function expressed as a percentage of the recovery of baseline contractile
      function was determined. Atrial trabeculae were randomized to control, hypoxic
      preconditioning (HPre), hypoxic postconditioning comprising either four 30-s
      (HPost-30) or 60-s (HPost-60) episodes of alternating hypoxia and reoxygenation,
      and HPost in the presence or absence of UO126 (a MEK1/2 inhibitor) or LY294002 (a
      PI3K inhibitor). HPre and HPost-60 improved the recovery of baseline contractile
      function (45.4+/-3.2% with HPre and 45.2+/-2.2% with HPost-60 vs 26.7+/-2.1 % in
      control: N>or=6/group: P<0.05), whereas HPost-30 failed to cardioprotect (28.3+/
      3.4% with HPost-30 vs 26.7+/-2.1 % in control: N>or=6/group: P>0.05). The
      cardioprotective effect of HPost-60 was abolished in the presence of either LY
      (28.1+/-2.5% with HPost-60+LY vs 45.2+/-2.2% with HPost-60: N>or=6/group: P<0.05)
      or UO (32.7+/-1.8% with HPost-60+UO vs 45.2+/-2.2% with HPost-60:N=7/group:
      P<0.05). The kinase inhibitors alone had no effect on functional recovery (28.2+/
      3.6% with LY and 30.1+/-4.8% with UO vs 26.7+/-2.1 % in control: N>or=5/group:
      P>0.05). In conclusion, we demonstrate for the first time that postconditioning
      protects human myocardium ex vivo and that this effect is dependent on the
      activation of the RISK pathway.

PMID- 17546528
TI  - Effects of contractile protein phosphorylation on force development in
      permeabilized rat cardiac myocytes.
AB  - The phosphorylation status of myofibrillar proteins influences the Ca(2+)
      responsiveness of the myofilaments,but the contribution of and the interaction
      between the individual components is poorly characterized. Therefore, in
      Langendorff perfused rat hearts (n=30), the phosphorylation levels of cardiac
      myosin binding protein-C (cMyBP-C), troponin I and T (cTnI, cTnT) and myosin
      light chain 1 and 2 (MLC-1, MLC-2) were determined by 1- and 2-dimensional gel
      electrophoresis. Isometric force development, its Ca(2+)-sensitivity, the rate of
      tension redevelopment (k(tr)) and passive force (F(pas)) were studied at optimal
      sarcomere length (2.2 microm) in mechanically isolated,permeabilized
      cardiomyocytes at 15 degrees C. Protein phosphorylation was varied by: 1)
      blocking spontaneous cardiac activity by lidocaine (0.35 mM; Quiescence); 2)
      electrical stimulation of the hearts at 5 Hz (Contraction) and 3. treatment of
      contracting hearts with Isoprenaline (1 microM). MLC-2 phosphorylation was
      increased in the Contraction group almost 2-fold, relative to the Quiescence
      group, whereas cMyBP-C and cTnI phosphorylation remained the same. Isoprenaline
      resulted in 3.7-fold increases in both cMyBP-C and cTnI phosphorylation, but did
      not result in a further increase in MLC-2 phosphorylation. No significant
      differences were found in maximum force and k(tr) between groups, both before and
      after protein kinase A (PKA) treatment. Ca(2+)-sensitivity in the Contraction and
      Isoprenaline groups was significantly reduced in comparison to the Quiescence
      group. These differences were largely abolished by PKA and F(pas) was reduced.
      These results highlight the impact of PKA-dependent phosphorylation on Ca(2+)
      sensitivity and provide evidence for an interaction between the effects of TnI
      and MLC-2 phosphorylation.

PMID- 17546529
TI  - Growth-differentiation factor-15 in cardiovascular disease: from bench to
      bedside, and back.

PMID- 17546530
TI  - Transgenic upregulation of IK1 in the mouse heart is proarrhythmic.
AB  - The role of the cardiac current Ik1 in arrhythmogenesis remains highly
      controversal. To gain further insights into the mechanisms of IK1 involvement in
      cardiac excitability, we studied the susceptibility of transgenic mice with
      altered IK1 to arrhythmia during various pharmacological and physiological
      challenges. Arrhythmogenesis was studied in transgenic mice expressing either
      dominant negative Kir2.1-AAA or wild type Kir2.1 subunits in the heart, models of
      IK1 suppression (AAA-TG) and up-regulation (WT-TG), respectively. Under normal
      conditions, both anesthetized wild type (WT) and AAA-TG mice did not display any
      spontaneous arrhythmias. In contrast,WT-TG mice displayed numerous arrhythmias of
      various types. In isolated hearts, the threshold concentration for halothane
      induced ventricular tachycardias (VT) was increased to 167% [corrected] in the
      AAA-TG and decreased to 54% [corrected] in WT-TG hearts when compared to WT
      hearts. The number of PVCs induced by AV node ablation combined with hypokalemia
      was reduced in AAA-TG hearts and increased in WT-TG mice. After AV node ablation
      AAA-TG hearts were more tolerant, and WT-TG less tolerant to isoproterenol-
      induced arrhythmias than WT hearts. Analysis of monophasic action potentials in
      isolated hearts shows a significant reduction in the dispersion of action
      potential repolarization in mice with suppressed IK1. The data strongly support
      the hypothesis that in the mouse heart upregulation of IK1 is proarrhythmic, and
      that under certain conditions IK1 blockade in cardiac myocytes may be a
      potentially useful antiarrhythmic strategy.

PMID- 17546531
TI  - [Self-help from the cyberspace?--An analysis of self-help forums for patients
      with bipolar affective disorders].
AB  - OBJECTIVE: The study aimed to evaluate if and how online self-help forums are
      used by patients with bipolar affective disorders. METHODS: Within a six-months
      period 1200 postings of 135 users in two German language forums were analysed
      with respect to fields of interest and self-help mechanisms. RESULTS: The topics
      most discussed were social network of the patients, symptoms of the illness, and
      medication. Disclosure, online-group cohesion as well as empathy and support were
      the main self-help mechanisms. CONCLUSIONS: Our study reveals that the social
      network is very important for patients coping with bipolar affective disorders.
      We infer that the main interest in participating in online forums for bipolar
      affective disorders is to share emotions. Attention to those aspects should be
      given also in psychoeducative programs.

PMID- 17546532
TI  - [Placement and treatment of mentally ill offenders--basic concepts and service
      provision in European Union Member States].
AB  - OBJECTIVE: Internationally, there is a variety of approaches and concepts for
      placing and treating mentally disordered offenders in forensic-psychiatric care.
      European overviews are missing. Major indicators have not been standardized yet,
      which is a serious obstacle for cross-boundary comparisons. METHODS: Basic
      concepts, legal frameworks, service provision and prevalences in forensic care of
      15 European Union Member States were assessed by an expert evaluation.
      Administrative data was compared and conclusions for a possible harmonization of
      approaches were drawn. RESULTS: The placement and treatment of mentally
      disordered offenders in the European Union Member States is characterized by a
      considerable variety of concepts and practice routines. National health reporting
      standards and the quality of available administrative data is poor. On the basis
      of available information, models of good practice are hard to choose.
      CONCLUSIONS: National and cross-boundary research should be intensified. Defining
      European quality and training standards in forensic psychiatry seems to be an
      activity to be started on a short term basis.

PMID- 17546533
TI  - [Is supplying homeless individuals with permanent housing effective? A
      prospective three year study on the course of mental health problems].
AB  - OBJECTIVE: Description of the three-year course of mental illness after supplying
      permanent housing to homeless individuals. METHODS: 109-male and 20 female
      homeless individuals were assessed at the assignment of permanent housing and at
      one and three year follow-up using the Structured Clinical Interview for DSM-IV.
      RESULTS: A high percentage (86 %) was able to maintain or even improve the index
      housing situation. Only minor changes were observed in mental illness severity
      and global functioning. Symptoms improved slightly over the three year period.
      High degrees of alcohol consumption and mental illness severity increased the
      risk of deterioration of the housing arrangement. CONCLUSIONS: Supplying homeless
      individuals with permanent housing is an effective measure but insufficient for
      improving mental illness. Combined measures of social and medical interventions
      from one provider are suggested for effective support of homeless people.

PMID- 17546534
TI  - [Is "Internet Addiction" a disorder of its own?--a study on subjects with
      excessive internet use].
AB  - OBJECTIVE: The term "Internet Addiction" implies that by using the pathological
      agent "Internet" an addiction-like behavior with a negative psychosocial outcome
      occurs. By using the pathogenetically more neutral term "Pathological Internet
      Use" (PIU) it is examined how frequently such behavior occurs in isolation and
      thus possibly as an independent condition and how often it occurs in the context
      of other psychiatric diseases. In the latter case PIU might merely be the
      consequence or a symptom of another underlying psychiatric disease. METHODS: 30
      persons with PIU were compared to 31 with intensive but not pathological internet
      use. A structured psychiatric diagnostic interview was carried out. RESULTS: The
      main finding is that in the group with PIU a psychiatric diagnosis was found in
      27 of 30 persons (e. g. anxiety disorders: 50.0 %). In the group without PIU only
      7 of 31 individuals (e. g. anxiety disorders: 12.9 %) had a psychiatric
      diagnosis. CONCLUSIONS: The finding that PIU occurs mostly in combination with
      other psychiatric diseases has a lot to commend against "Internet addiction" as a
      frequent and independent disease and gives reason for further in-depth studies to
      consider other psychiatric disorders in people exhibiting PIU with regard to
      diagnosis and therapy.

PMID- 17546535
TI  - Endoscopic treatment of lumbar arachnoiditis.
AB  - OBJECTIVE: The diagnosis of lumbar arachnoiditis remains complex and often
      inconclusive. Using the technique of lumbar subarachnoidal endoscopy
      (thecaloscopy), the pathology can be identified and the patient treated with long
      term effects on the symptoms. METHOD: Endoscopic operations were performed on 23
      patients suffering from varying symptoms with an enlarged lumbar subarachnoidal
      space. Having confirmed the diagnosis of lumbar arachnoiditis, a number of
      endoscopic operations ranging from adhesiolysis to subarachno-epidurostomy were
      carried out. RESULTS: Radicular symptoms in lumbar arachnoiditis were
      successfully relieved by various endoscopic dissection techniques, such as
      restoration of the improved CSF flow by subarachno-epidurostomy along the
      rootlet. This has been identified as one of the causal factors of the clinical
      symptoms. In cases where lumbar pain persists in spite of a previous
      thecaloscopy, further treatment with a lumboperitoneal shunt device has proved
      most successful.

PMID- 17546536
TI  - Keyhole approach for posterior cervical discectomy: experience on 84 patients.
AB  - Anterior cervical discectomy with or without fusion has been commonly used for
      cervical disc disease since the description by Smith and Robinson in 1958. In
      this report, surgical technique, advantages, and disadvantages of the posterior
      approach, known as the posterior keyhole laminotomy-foraminotomy, are reviewed
      and motion versus fusion surgery discussed. Between 1996 and 2004, the keyhole
      laminotomy-foraminotomy was performed on 84 patients suffering from lateral
      cervical soft disc herniation or osteophytes. All the procedures were performed
      under the surgical microscope. A high-speed drill was used for drilling the bone.
      In 49 patients (58%), soft disc herniation was removed, while in 35 patients
      (42%) there were osteophytes. Successful relief of radiculopathy symptoms was
      achieved in 80 patients (96%). In 4 patients the symptoms recurred. One patient
      (1.2%) developed kyphosis. The only complication observed intraoperatively was a
      partial root injury in one patient (1.2%). Mean hospitalization time was 48
      hours. The posterior approach is particularly appropriate in patients whose root
      compression is located posterolaterally. Advantages of this surgery are minimal
      lamina resection, good visualization of the nerve root, postoperative early
      mobilization and minimal hospitalization. Microsurgery enables us to both
      preserve the motion of operated segment and avoid cervical instability.

PMID- 17546537
TI  - Vertebroplasty in the treatment of osteoporotic vertebral fractures: results and
      functional outcome in a series of 175 consecutive patients.
AB  - Osteoporosis is the most common cause of vertebral collapse, which significantly
      impairs mobility and quality of life. Primary management consists of conservative
      therapeutic measures such as analgesics, bed rest, external bracing and
      rehabilitation. Percutaneous vertebroplasty for the treatment of osteoporotic
      compressive fractures has gained popularity during the last decade. The limited
      invasiveness and encouraging results of vertebroplasty obtained in the treatment
      of patients with symptomatic osteoporotic compression fractures have favored an
      extensive use of the procedure for the management of patients with disabling pain
      refractory to conservative therapy. In the present paper, the authors provide
      procedure results and functional outcomes in a series of 175 consecutive patients
      with 242 symptomatic osteoporotic vertebral compression fractures treated by
      means of percutaneous polymethylmethacrylate vertebroplasty.

PMID- 17546538
TI  - Minimally invasive decompression for lumbar spinal canal stenosis in younger age
      patients could lead to higher stresses in the remaining neural arch -- a finite
      element investigation.
AB  - BACKGROUND AND PURPOSE: A young patient group with the symptoms of acquired
      spinal stenosis has been identified recently in the literature. The patients
      between 25-50 years of age were found to have signs of lumbar spinal stenosis
      because of degenerative spinal changes. Some of them were operated on using the
      same limited decompression approaches as the older patients. However, this group
      differs from the geriatric population due to the scarcity of remodeling
      degenerative signs at the spine. Therefore, the possible ligamentous laxity,
      facet joint degeneration or only the removal of some spinal structures could lead
      to the increased stresses in the remaining spinal arch and could have an
      unfavorable course of events after the procedure. A biomechanical study has been
      done using an experimentally validated finite element model (FEM) of the intact
      L3-S1 lumbar spine to elucidate the influence of the limited decompression on
      range of motion (ROM) and stress distribution on the neural arch in this patient
      group. METHODS: We simulated unilateral laminotomy L4 and medial facetectomy L4
      5, medial facetectomy L4-5 and lateral fenestration of L5 pars interarticularis,
      combined transarticular lateral and medial approach with partial facetectomy L4
      5, "port-hole" decompression at the L4 level, and hemilaminectomy L4 with medial
      facetectomy L4-5. The ROM and maximum von Mises stresses were analyzed in
      flexion, extension, lateral bending, and axial rotation in response to a 10.6 Nm
      moment with 400 N axial compression. The data were compared with the intact spine
      and hemilaminectomy L4 with medial facetectomy L4-5 models. RESULTS AND
      CONCLUSION: The investigation revealed almost the same ROM after simulation but a
      considerable increase in stresses at both the pars interarticularis and the
      inferior facet after limited decompressions, especially in extension and rotation
      to the contralateral side. Stresses at the contralateral L4 pedicle were highest
      after L4 hemilaminectomy and medial facetectomy L4-5. Due to the observed
      increases in stresses, the surgeon should be aware of the possibilities of stress
      fractures in this patient group.

PMID- 17546539
TI  - Severe cerebral vasospasm caused by non-aneurysmal subarachnoid hemorrhage
      treatment with transluminal balloon angioplasty.
AB  - Non-aneurysmal subarachnoid hemorrhage (NSAH) is a benign form of subarachnoid
      hemorrhage (SAH). The angiographic changes of cerebral vasospasm (CVS) are
      uncommon in patients with this type of SAH. NSAH is uniformly associated with an
      excellent outcome without associated rebleeding or symptomatic CVS. We report a
      patient with NSAH who developed severe and diffuse CVS. He was treated with
      transluminal balloon angioplasty because he has been refractory to conventional
      treatment measures for CVS.

PMID- 17546540
TI  - Virtual endoscope-assisted intracranial aneurysm surgery: evaluation of fifty
      eight surgical cases.
AB  - OBJECTIVE: Better visualization of the intracranial aneurysm may improve surgical
      outcomes. To this aim, we evaluated the effectiveness of using virtual endoscopy
      (VE) during intracranial aneurysm surgery. METHODS: Fifty-eight patients with 63
      intracranial aneurysms were enrolled in this study. Every patient was examined by
      digital subtraction angiography (DSA) and a randomly selected twenty-six cases
      were also examined by computed tomography (CT). CT angiography data were linked
      via imaging software for reconstruction of VE images. All patients were operated
      on using standard microsurgical procedures. Among these cases, randomly selected
      cohorts of twenty-six patients with 28 intracranial aneurysms were operated on
      also using VE-assisted surgical procedures. The surgical results of both groups
      were compared to determine the efficacy of the VE-assisted surgical procedure.
      RESULTS: Aneurysm locations, surgical timing and Hunt-Hess grade distribution
      were not statistically significant between both groups (p=0.948). However,
      significantly reduced complication rates and increased post-operative Glasgow
      outcome scores were observed in the VE group (p<0.05) compared to control.
      CONCLUSION: Aneurysms and surrounding anatomic structures were well depicted by
      VE in three dimensions with interactive fly-through views. This method improved
      our surgical results by improving visualization of the aneurysm and increasing
      surgical orientation. We report that this method can be very helpful to surgeons
      during intracranial aneurysm surgery and may reduce post-surgical complications.

PMID- 17546541
TI  - Laparoscopic neurolysis of the sacral plexus and the sciatic nerve for extensive
      endometriosis of the pelvic wall.
AB  - BACKGROUND: The aim of this study is to report on the feasibility of laparoscopic
      neurolysis of the plexus sacralis and the sciatic nerve in deep endometriotic
      infiltration of the lateral pelvic wall. METHODS: A transperitoneal approach to
      the pelvic nerves combined with the LANN technique for intraoperative assessment
      of the function of the exposed nerves permit exposure and sparing of all somatic
      nerves during resection of the endometriotic lesion. RESULTS: We report on our
      short experience with 21 patients who underwent this technique for the treatment
      of endometriotic infiltration of the sacral plexus at different levels.
      CONCLUSION: In young patients with chronic unilateral sciatica or unilateral
      pudendal neuralgia - Alcock's canal syndrome - where no neurological/orthopedic
      etiologies have been found, endometriotic infiltration of the lateral pelvic wall
      has to be implicated as a potential etiology and an indication for laparoscopy
      must be discussed. Laparoscopic neurolysis of the pelvic somatic nerves is a
      feasible procedure for trained laparoscopic surgeons who have a good knowledge of
      the retroperitoneal pelvic (neuro)anatomy.

PMID- 17546542
TI  - Display of the epileptogenic zone on the frontal cortical surface using dynamic
      voltage topography of ictal electrocorticographic discharges.
AB  - To evaluate the usefulness of computerized brain-surface dynamic voltage
      topography (DVT) of ictal electrocorticographic (ECoG) discharges to localize and
      identify epileptogenic areas, 3 patients with intractable frontal lobe epilepsy
      who underwent epilepsy surgery after chronic subdural electrode recording were
      assessed. Cortical surfaces and subdural electrodes were photographed during
      initial surgery to create an electrode map that could be superimposed onto a
      picture of the brain surface. DVT was performed by calculating sequential
      amplitudes of ictal ECoG discharges, which were then superimposed onto the
      cortical and electrode maps. In all cases, DVT clearly identified the ictal onset
      zone and the early propagation area on the operative field. DVT allowed
      recognition of spatial relationships between the epileptogenic area and
      structural abnormalities, functional cortex, and cortical veins; and was useful
      to decide on the resection area.

PMID- 17546543
TI  - Evolution of a focal brain lesion produced by interlaced microplanar X-rays.
AB  - Stereotactic radiosurgery has led to advances in the treatment of central nervous
      system disease. It relies upon the principle of delivering relatively high dose
      irradiation to a precise target, while exposing surrounding tissues to extremely
      low doses. We describe a novel radiosurgical approach using interlaced
      microplanar X-rays which we have termed "microradiosurgery." The use of
      microbeams allows for 1,000-times greater precision than current clinically
      employed techniques. As a demonstration of this new method, we produced a
      approximately 3.8 mm (3) lesion in the rat brain. The lesion was followed over a
      period of 216 days using 9.4 Tesla magnetic resonance imaging. Our results show a
      gradually developing lesion at the site of the interlaced beams. The lesion began
      as a high T2 signal only, but advanced to include a central area of low T1 and
      mixed T2 signal within 2 months. No lesion was observed in the other side of the
      brain which was exposed to non-interlaced microbeams only. Interlaced microbeams
      is an effective method to create focal brain microlesions. This technique may
      allow the future treatment of pathology not accessible by surgical or more
      traditional radiosurgical means.

PMID- 17546544
TI  - Is endoscopic third ventriculostomy an internal shunt alone?
AB  - OBJECTS: This study was made to define the mechanism of endoscopic third
      ventriculostomy (ETV) in the various forms of hydrocephalus. METHODS: One hundred
      and forty patients with various forms of hydrocephalus treated by ETV are
      reviewed. The series includes 75 cases (53.5%) of triventricular obstructive
      hydrocephalus (group 1), 20 (14.3%) with hydrocephalus following CSF infection or
      hemorrhage (group 2) and 45 (32.3%) with idiopathic normal pressure hydrocephalus
      (group 3). Factors which have been considered include type and etiology of the
      hydrocephalus, intraoperative evidence of downward and upward movement of the
      third ventricular floor after the stomy, patient outcome and rate of shunt
      independent cases. RESULTS: The overall rate of successful ETV was 79.3% (111/140
      shunt-free patients). The success rate was 88% (66/75) in group 1, 60% (12/20) in
      group 2 and 73.4% (33/45) in group 3. The intraoperative finding of significant
      movement of the third ventricular floor after the stomy was evidenced in 121/140
      cases (86.4%) and particularly in all cases of group 1, in 9/20 (45%) of group 2
      and in 37/45 (82%) of group 3. CONCLUSIONS: The relatively high rate of success
      of ETV in various forms of hydrocephalus and the intraoperative finding of
      mobility of the third ventricle floor after the stomy suggest that the first
      mechanism of the ETV is the restoration of pulsatility of the ventricular walls.
      This results in restoration of the CSF flow from the ventricular system into the
      subarachnoid spaces and normalization of the CSF dynamics. Accordingly, ETV is
      not only an internal shunt, but it primarily influences the capacity of the brain
      pulsatility to ensure CSF flow.

PMID- 17546545
TI  - Cerebrospinal fluid composition modifications after neuroendoscopic procedures.
AB  - Normal saline solution is currently used as the ventricular irrigation fluid
      during neuroendoscopic procedures. The aim of this study is to determine the
      alterations in the cerebrospinal fluid (CSF) composition after neuroendoscopic
      interventions. Twenty nine patients who underwent a neuroendoscopic procedure
      under general anaesthesia were studied. Temperature inside the cerebral ventricle
      was measured and samples of CSF were taken to determinate oxygen and carbon
      dioxide partial pressures, pH, base excess, ionised calcium, standard
      bicarbonate, glucose, sodium, potassium, magnesium, total calcium, proteins,
      chlorine and osmolality before initiating the irrigation and after the
      neuronavigation. Patient demographics, neuronavigation time, total fluid volume
      used and temperature of the irrigation solution and complications that appeared
      in the first 24 hours were collected. Mean age of the patients was 42+/-18 years.
      The mean neuronavigation time was 21.5+/-15.4 minutes. The mean amount of saline
      solution used for irrigation was 919.6+/-994.7 mL. All the values studied in the
      CSF, except osmolality, showed significant variations. There was a significant
      correlation between the CSF variation of pH, oxygen and carbon dioxide partial
      pressures, base excess, standard bicarbonate, glucose and total calcium with
      respect to the total volume of irrigation solution, but not with respect to the
      neuronavigation time. A cut-off point of 500 mL of irrigation solution
      (sensitivity 0.7; specificity 0.87) was related with a CSF pH decrease greater
      than 0.2. The use of saline as irrigation solution during neuroendoscopic
      procedures produces important changes in CSF.

PMID- 17546546
TI  - Exceptional symptomatology of a lipoma beneath the third ventricular floor and
      successful neuroendoscopic treatment.
AB  - The aim of this paper is to present the exceptional case of a lipoma located
      beneath the floor of the third ventricle in front of right mamillary body
      manifesting with psychiatric symptoms and treated by navigated neuroendoscopy. A
      58-year-old male was referred for neurosurgical treatment because of paroxysmal
      disturbances of consciousness accompanied by aggressive behaviour. Because
      electroencephalographic evaluation failed to confirm the epileptic origin of the
      presenting symptoms, the final psychiatric diagnosis was syndrome of amentia.
      However, when the MRI investigation revealed two tiny lipomas with one of them
      located in front of the right mamillary body, a hypothesis was established that
      this lipoma might be the cause of the clinical symptoms. After a thorough
      analysis of the patient's symptoms and taking into special consideration the
      functional role of hypothalamic structures the decision to remove the lipoma
      endoscopically was accepted. After stereotactic planning and functional
      correlation using digital stereotactic atlases, the lipoma located in front of
      the right mamillary body was endoscopically removed. The clinical course after
      navigated neuroendoscopic surgery proved complete disappearance of symptoms and
      problems supported by the results of imaging techniques, psychological
      investigations and neurological findings. Detailed anatomic analysis with
      pathophysiological consideration substantiated the excellent result of minimally
      invasive endoscopic surgery for lipoma removal.

PMID- 17546547
TI  - Depth-mark taping on neurosurgical instruments for brain tumor surgery: technical
      note.
AB  - The authors present a method for applying sterile surgical tape to neurosurgical
      instruments (suckers and/or ultrasonic surgical implements) as depth gauges in
      brain tumor surgery. This simple and inexpensive modification is helpful in the
      achievement of gross anatomic orientation in situations where it is difficult to
      find anatomic landmarks, e.g., with initial detachment of large meningiomas from
      the dura in the deep region.

PMID- 17546548
TI  - Laparoscopic placement of ventriculoperitoneal shunts: an innovative
      simplification of the existing techniques.
AB  - Ventriculoperitoneal shunting (VPS) remains one of the alternative choices for
      the surgical treatment of hydrocephalus. During the last two decades laparoscopy
      has been utilized to facilitate the placement of the abdominal portion of the
      shunt. We describe a minimally invasive laparoscopic technique, which facilitates
      the rapid, safe and direct placement of the peritoneal component of the VPS. A
      side frontal ventricular catheter is placed through a small burr hole and
      connected to the valve at the postauricular region. An infra-umbilical trocar is
      placed, using the Hasson technique, and after the pneumoperitoneum is
      established, a 10-mm laparoscope is introduced for identification of a VPS entry
      side free of adhesions. A 5-mm skin incision is made at the decided point of
      catheter insertion, usually at the right upper quadrant. Using a tunneler, the
      VPS catheter is placed subcutaneously from abdomen insertion point, to the
      postauricular region, where it is connected to the valve. A split type, 10-12 Fr
      and 12-15 cm long metallic puncture cannula, like those used for suprapelvic
      percutaneous bladder drainage, is introduced into the abdomen. Under direct
      laparoscopic vision the peritoneal portion of the VPS is passed into the abdomen
      through the cannula. The catheter is leaded to a desirable location by pointing
      the needle accordingly. Alteration of the position of the catheter can also be
      attained by entraining the catheter with the laparoscope and without using
      auxiliary graspers. The function of the VPS is confirmed under direct
      visualization. Suturing the abdominal and cranial incisions completes the
      procedure. We used this technique in a series of 12 patients with excellent
      outcome. There were no intra- or postoperative complications and no mortalities.
      Our technique is less invasive than a minilaparotomy, embraces all laparoscopic
      benefits and does not require auxiliary forceps or guidewires. It uses easy
      available materials with low cost, and attains an easy, rapid, and safe placement
      of the abdominal portion of the VPS.

PMID- 17546549
TI  - [Career profiles of physicians in our time. Speech of the president of the DGTHG
      on the occasion of the 36th annual convention of the DGTHG 2007 in Hamburg].

PMID- 17546550
TI  - [Politics and science: a view into the history of organ transplantation in
      Russia].

PMID- 17546551
TI  - Extracorporeal membrane oxygenation: experience in an adult medical ICU.
AB  - BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is a technology that can
      provide extracorporeal gas exchange to patients with severe pulmonary or cardiac
      dysfunction. We report on our clinical experience with ECMO in critically ill
      patients. METHODS: We performed a retrospective analysis of 23 patients treated
      with ECMO in a medical intensive care unit in a tertiary referral academic
      centre. RESULTS: 13 patients were considered immunocompetent and 10 were
      immunocompromised when extracorporeal membrane oxygenation was started. 16
      patients presented with acute respiratory distress syndrome (ARDS), 2 patients
      had intractable cardiac failure, and 5 patients had combined respiratory and
      cardiac failure. In 16 patients, a veno-venous bypass was constructed; in 7
      patients, the initial bypass was venoarterial. 11 patients survived. In 2
      patients technical complications were fatal. CONCLUSIONS: Our data indicate that
      patients with community-acquired pneumonia and no underlying disease will benefit
      most from this technique. However, long-term survival is possible in
      immunocompromised patients. Venoarterial bypass can carry a higher risk for
      technical complications. Increasing experience apparently also reduces the risk
      of technical complications.

PMID- 17546552
TI  - Regurgitation of the atrioventricular valves after corrective surgery for
      complete atrioventricular septal defects - comparison of different surgical
      techniques.
AB  - OBJECTIVE: Different surgical approaches have been used to repair complete
      atrioventricular septal defects (AVSD). Regurgitant atrioventricular valves (AV
      valves) are common after surgery. We compared different surgical techniques with
      respect to long-term postoperative AV-valve regurgitation. METHODS: In 69
      patients with complete AVSD, three different surgical techniques were applied:
      Single-patch, two-patch, and modified techniques. The left-sided AV-valve cleft
      was surgically closed in all patients. RESULTS: A comparison of the results of
      the different techniques showed no difference in the degree of AV-valve
      regurgitation on either the right or the left side. The average degree was mild
      on both sides. Only one patient needed reoperation for severe left-sided AV-valve
      regurgitation. CONCLUSION: The different surgical techniques used for the
      correction of AVSD do not have a major bearing on the degree of AV-valve
      regurgitation.

PMID- 17546553
TI  - Recombinant hirudin for cardiopulmonary bypass anticoagulation: a randomized,
      prospective, and heparin-controlled pilot study.
AB  - BACKGROUND: Lepirudin, a recombinant hirudin, is a direct acting thrombin
      inhibitor that has been used as a heparin alternative in patients with heparin
      induced thrombocytopenia requiring on-pump cardiac surgery. To evaluate the
      efficacy, safety, and clinical utility of lepirudin as a cardiopulmonary bypass
      (CPB) anticoagulant, we compared lepirudin with heparin in a routine CPB setting.
      METHODS: Twenty patients were randomly assigned to receive lepirudin (0.25 mg/kg
      b. w. bolus and 0.2 mg/kg b. w. added to the CPB priming) or heparin (400 U/kg b.
      w. bolus) with protamine reversal. Lepirudin and heparin anticoagulation during
      CPB was monitored using the ecarin clotting time or ACT, respectively and
      additional lepirudin (5 mg) or heparin (5000 U) boluses were administered.
      RESULTS: The CPB circuit was performed in both groups without thromboembolic
      complications. Median blood loss during the first 36 hours was statistically
      higher ( P = 0.007) in the lepirudin group (1.226 +/- 316 ml) compared to the
      heparin group (869 +/- 189 ml). One patient of the lepirudin group developed
      pulmonary embolism 24 hours after surgery. This patient was tested homozygous for
      the FV-Leiden mutation. CONCLUSION: Lepirudin provides effective CPB
      anticoagulation but induces a higher postoperative blood loss than heparin.
      Lepirudin should be restricted to patients undergoing CPB who cannot be exposed
      to heparin.

PMID- 17546554
TI  - Artificial chordae for mitral valve repair: mid-term clinical and
      echocardiographic results.
AB  - BACKGROUND: This paper reports on the mid-term clinical and echocardiographic
      results of mitral valve repair with chordal replacement. METHODS: Sixty-nine
      patients (mean age 61 +/- 14 years) underwent mitral valve repair with chordal
      replacement. The etiology was degenerative in 53 (77 %), rheumatic in 7 (10 %),
      ischemic in 6 (9 %) and infective in 3 (4 %). Mean ejection fraction was 58 +/-
      14. In 35 patients (51 %), a minimally invasive approach was used. Mean follow-up
      time was 45 +/- 27 months. RESULTS: Anterior leaflet chordae were replaced in 58
      (84 %) patients. There were 3 operative deaths. Freedom from non-trivial
      recurrent mitral regurgitation (MR) was 81.3 +/- 8.7 % at 97 months. Follow-up
      echocardiographic controls showed mild recurrent MR in 5 (8 %) patients and
      moderate in 2 (3.2 %). These two patients required reoperation due to mitral
      annulus redilation after suture annuloplasty. Competent neochordae were found at
      reoperation. Freedom from reoperation at 97 months was 96.6 +/- 2.4 %. Four
      patients died during follow-up resulting in an actuarial survival of 87 +/- 6.2
      %. CONCLUSION: The replacement of chordae tendineae with ePTFE sutures during
      mitral valve repair has shown good mid-term results. The implantation of the
      neochordae can be also performed safely using minimally invasive procedures.

PMID- 17546555
TI  - Thoracic surgical operations performed under local anesthesia and sedation for
      diagnosis and treatment.
AB  - Generally, the operative procedures for the diagnosis or treatment of
      mediastinal, intrathoracic and/or chest wall lesions requiring rib resection are
      performed under general anesthesia. Although evidence suggests that thoracoscopy
      can be performed under local anesthesia, no report has indicated that some major
      thoracic procedures can be accomplished without general anesthesia. In our study,
      we advocate that certain surgical procedures could be performed under local
      anesthesia with a performance similar to that of general anesthesia. Thirty
      patients underwent thoracic procedures with local anesthesia and sedation for
      diagnosis and treatment. Seventeen of the patients were men, and the mean age of
      the patients was 49.6 years (range 16 to 71 years). There were 13 diagnostic
      procedures, and 17 procedures were for treatment purposes. The operative
      procedures performed using only local anesthesia were mini-thoracotomy (n = 9),
      mediastinotomy (n = 4), revision of a full-thickness posterolateral thoracic
      incision (n = 7), resection of the chondroma (n = 4), Eloesser flap (n = 1),
      metastasectomy of the chest wall (n = 3), empyectomy (n = 1), and video-assisted
      thoracoscopy (n = 2). Severity of pain was evaluated by VAS. There were no oral
      or intravenous analgesic requirements in the early postoperative period. No
      complications attributable to the procedure were observed. Thoracic surgical
      procedures for diagnosis and treatment performed under local anesthesia are
      simple, effective, economical and comfortable for the patient.

PMID- 17546556
TI  - Foreign bodies aspirated in children: role of bronchoscopy.
AB  - OBJECTIVE: To examine the diagnostic and therapeutic role of fiber-optic and
      rigid bronchoscopy in pediatric patients with foreign body inhalations. METHODS:
      From January 1986 to December 2004, we observed 128 young patients with suspicion
      of foreign body aspiration. Patients were divided into 3 groups: group I,
      patients with negative chest X-ray; group II, patients with radiological direct
      signs; group III, patients with radiological indirect signs. RESULTS: Removal of
      the foreign body was effected in 105 patients by rigid bronchoscopy and in 13
      patients by fiber-optic bronchoscopy. In 3 group II patients a thoracotomy with a
      bronchotomy was necessary. CONCLUSIONS: Fiber-optic bronchoscopy showed a
      diagnostic accuracy rate of 100 % but played a poor therapeutic role with a case
      resolution of 10.7 %. Rigid bronchoscopy was the main technique, permitting the
      removal of the tracheobronchial foreign body in 97.2 % of patients.

PMID- 17546557
TI  - Prediction of cardiopulmonary morbidity after resection for lung cancer: stair
      climbing test complications after lung cancer surgery.
AB  - BACKGROUND: The objective of this study was to assess the role of a modified
      stair climbing test in predicting postoperative cardiopulmonary complications.
      METHODS: A consecutive series of 150 patients who had undergone pulmonary
      resection for lung carcinoma formed the prospective database of this study. All
      patients performed a preoperative modified stair climbing test. Univariate and
      multivariate analyses were performed to identify predictors of postoperative
      cardiopulmonary complications. RESULTS: With univariate analysis, the patients
      with complications had a lower pre-exercise and postexercise percentage of oxygen
      saturation. PaO (2) levels were found to be lower and a greater change in oxygen
      desaturation during exercise was noted. Logistic regression analysis showed that
      the percent of oxygen saturation pre-exercise and the change in percent of oxygen
      desaturation during exercise were independent and reliable predictors of
      cardiopulmonary morbidity. CONCLUSIONS: A modified stair climbing test is a safe,
      economical and simple test capable of predicting cardiopulmonary complications.

PMID- 17546558
TI  - Successful treatment of mucormycosis endocarditis complicated by pulmonary
      involvement.
AB  - Cardiac mucormycosis is an exceedingly rare condition. This case report describes
      mucormycosis endocarditis in an immunocompromised patient with ulcerative
      colitis. His condition was further complicated by multiple septic emboli to the
      lungs. His management included surgical excision of the right atrial endocarditic
      vegetation and antifungal treatment with high-dose liposomal amphotericin B.

PMID- 17546559
TI  - A new technique of myocardial protection during aortic root replacement:
      antegrade/retrograde coronary perfusion.
AB  - Aortic root surgery has traditionally been performed with an arrested and cooled
      heart using cardioplegia. A new technique of myocardial protection was utilized
      in the treatment of ascending aortic aneurysm with severe aortic valve
      regurgitation requiring aortic root replacement with the Cabrol technique.
      Retrograde and antegrade perfusion of the heart with blood allowed the surgical
      operation to be performed safely while the heart was beating and eliminated the
      ischemic reperfusion injury which occurs during cardioplegic arrest and
      reinstitution of blood perfusion after removal of the aortic cross-clamping
      required in traditional techniques.

PMID- 17546560
TI  - Surgical management in paediatric patients with left abnormal subclavian artery
      and right aortic arch.
AB  - Left abnormal subclavian artery and right aortic arch is described as a rare
      cause of dyspnoea and dysphagia in paediatric patients. The optimal surgical
      management of such cases is not clearly established. We propose a single-stage
      repair by transection of the patent ductus arteriosus or ligamentum arteriosum
      and an additional transection of the left abnormal subclavian artery with
      reimplantation into the common carotid artery.

PMID- 17546561
TI  - Telematics in medicine: a network infrastructure to optimize processes in
      cardiology and heart surgery.
AB  - OBJECTIVES: During the past 2 decades, cardiac surgery has developed into a high
      tech field. Increasing numbers of urgent surgical procedures mean that the time
      interval from diagnosis to surgical treatment must become ever shorter.
      Optimizing inconvenient and slow processes such as postal correspondence by using
      internet services is therefore mandatory in current cardiosurgical practice, and
      this includes the electronic transfer of patient data and diagnostic imaging
      material [12]. This study focuses on the internet connection of several cardiac
      referral centers to a cardiosurgical institution. METHODS: Eleven cath lab
      centers were connected to a cardiosurgical center by internet. Auser program was
      especially developed to optimize connecting processes with the department. Data
      conversion was based on HL7 codes and angiograms were based on CD-ROM mediums and
      the DICOM standard. An online registration based on the HL7 communications
      standard was provided. RESULTS: All cath lab centers were successfully connected
      to the cardiosurgical institution. Angiography data were transmitted within 30 +/
      15minutes. The time interval from diagnosis to decision for surgery decreased
      from 36 +/- 13 hours to 1 +/- 0.5 hours (p = 0.01). Urgent or emergent surgery
      could be provided after 18 +/- 19 hours, compared to 56 +/- 35 hours before (p =
      0.02). CONCLUSION: Special programs transmitting data via the internet
      significantly reduces the time interval from diagnosis to surgical treatment.
      Standardizing data transmitting processes from referral centers markedly
      optimizes cardiological and cardiosurgical treatments and could thereby improve
      survival rates and reduce costs.

PMID- 17546562
TI  - Secondary endovascular repair of a reconstructed superior vena cava in a patient
      with a malignant thymic epithelial neoplasm.
AB  - Thymic epithelial tumors can cause venous obstruction from compression or direct
      invasion of the superior vena cava (SVC) or the innominate veins. We report a
      case of a 40-year-old patient with a Masaoka stage III thymoma that resulted in
      obstruction of the left innominate vein and extrinsic compression of the SVC. All
      macroscopic tumors were resected together with ligation of the left innominate
      vein and reconstruction of the SVC with an ePTFE graft. Early graft thrombosis
      occurred in the first postoperative month with clinical signs of SVC syndrome.
      Endovascular repair was performed with the deployment of self-expanding nitinol
      stents, resulting in immediate relief of symptoms. The stented graft has remained
      patent for a follow-up period of 7 months.

PMID- 17546563
TI  - Synchronous thymoma and lung carcinoma resected via median sternotomy with VATS
      guidance.
AB  - Synchronous tumours of the thymus and lung are rare. We describe the case of a 57
      year-old gentleman, who presented with a large type AB thymoma in the superior
      anterior mediastinum and a primary bronchogenic adenocarcinoma in the right upper
      lobe. In view of this, he underwent surgical resection of the thymoma directly
      through amedian sternotomy and right upper lobectomy via the median sternotomy
      with video assisted thoracoscopic guidance.

PMID- 17546564
TI  - Giant intraosseous lipoma of the rib.
AB  - Lipoma is defined as a benign tumor consisting of a circumscribed mass of adipose
      tissue. Intraosseous lipomas represent fewer than 0.08% of all primary bone
      tumors. We present an unusual case of intraosseous lipoma arising from the left
      10th and 11th ribs and extending to the subdiaphragmatic area and abdomen. Lipoma
      of the rib is an extremely rare disorder presenting diagnostic challenges.

PMID- 17546565
TI  - Chylothorax following extended thymectomy for myasthenia gravis.
AB  - The effectiveness of extended thymectomy for the treatment of myasthenia gravis
      is well documented. Most of the postoperative complications have been related to
      respiratory distress or wound complication, but chylothorax following thymectomy
      has been reported as a rare complication. From January 1995 to December 2004, 217
      patients underwent extended thymectomy for myasthenia gravis at Taipei Veterans
      General Hospital. Three cases (1.38%) developed chylothorax after operation.
      Injury to the unseen division of the mediastinal lymphatics and branches from the
      thoracic duct during extensive dissection of perithymic fat tissue, which is
      seldom performed in classical thymothymectomy procedures, may have been the main
      cause of this complication. Two of the cases received conservative treatment and
      recovered uneventfully. The other patient (0.46%) underwent ligation of the
      thoracic duct 3 months later, which also resulted in the complication being
      cured. CONCLUSIONS: Post-thymectomy chylothorax is rare and seems to be related
      to extended thymectomy. Even a small invasive procedure such as VATS for extended
      thymectomy formyasthenia gravis could be complicated by chylothorax. We recommend
      that if chylothorax develops after thymectomy, conservative treatment is the
      treatment of choice; however, thoracic duct ligation is a useful method for
      treating long-term unhealed chylothorax.

PMID- 17546566
TI  - Supradiaphragmatic ectopic liver: delayed traumatic hepatic hernia mimics
      pulmonary tumor.
AB  - We present a rare case of a 63-year-old woman, the oldest one in the literature,
      with supradiaphragmatic ectopic liver that mimics a pulmonary nodule. The chest
      roentgenogram and chest computer tomography showed a lobulated tumor nearby the
      diaphragm. Pathological examination of the resected tumor disclosed only
      remarkable fatty liver change. Ectopic liver should be kept in mind to
      differentiate for the pulmonary tumor nearby the diaphragm.

PMID- 17546567
TI  - [Intensive care medicine].

PMID- 17546569
TI  - [Pulmonary rehabilitation in COPD].
AB  - COPD as a widespread disease will need much more attention of all health care
      providers in future. Otherwise COPD could lead to increasing costs, especially
      caused by the systemic nature of this disease and the large number of
      comorbidities as well as an increase of morbidity with reduced personal fitness
      and quality of life. As a result, the occupational and social participation
      subsequently decrease. Specific diagnostic in rehabilitation shows these
      consequences and a multimodal, multi-professional therapeutic management can be
      started. This means an optimized pharmacotherapy, different steps of intensity of
      indoor or outdoor rehabilitation with a training for patients, withdrawal
      therapy, psycho-social support and in severe cases non invasive artificial
      respiration. The indication for rehabilitation and the legal requirements are
      shown, as well as the ways to get rehabilitation and the possibilities of a
      rehabilitation chain including rehabilitation follow up and physical training. It
      has been proved that rehabilitation improves the symptoms of the disease, the
      personal fitness and the quality of life. Futhermore, rehabilitation reduces the
      days and the time spent in hospital and eventually reduces fear and depression.
      Therefore if consequently followed, rehabilitation in COPD is a valid therapeutic
      measure that can diminish the epidemiologic burden of this widespread disease.

PMID- 17546570
TI  - [The critically ill patient with COPD].

PMID- 17546571
TI  - Antipyretic drug use in children in French office based medical practice.
AB  - PURPOSE: To analyse antipyretics (APs) prescriptions profile in children,
      particularly the frequency of AP combinations. METHODS: APs (acetylsalicylic
      acid, paracetamol, ibuprofen or ketoprofen) prescribed to children below 12 years
      and refunded by a public health insurer in 2003, throughout France, were
      examined. RESULTS: A total of 513 034 prescriptions were refunded for 240 720
      children. The mean number of AP prescriptions per child was the highest in
      children aged 6 months to 2 years. Paracetamol was the main AP prescribed, but
      its prescription declined with age, from 90.8% below 3 months old to 57.4%
      between 6 and 12 years old. Ibuprofen-only prescriptions were rare below 3 months
      and maximal between 2 and 6 years. The ibuprofen/paracetamol combination was
      prescribed from 6 months old, and its frequency was maximal between 2 and 6 years
      old (21.7%). CONCLUSIONS: The clear predominance of paracetamol prescriptions
      suggests that French prescribers are relatively aware of the relative risk
      benefit ratio of the different APs. Studies are required to determine if the APs
      are prescribed to be used alternately or when a monotherapy fails. Guidelines to
      manage fever in children are needed in France to restrict APs combination to the
      case of paracetamol failure.

PMID- 17546572
TI  - A quantitative approach to benefit-risk assessment of medicines--part 1: the
      development of a new model using multi-criteria decision analysis; part 2: the
      practical application of a new model.

PMID- 17546573
TI  - A quantitative approach to benefit-risk assessment of medicines - part 1: the
      development of a new model using multi-criteria decision analysis.
AB  - PURPOSE: One of the most important uses of benefit-risk assessment pertains to
      approval of new medicines by regulatory authorities and the subsequent review of
      these products during their life-cycle when new safety and/or efficacy data
      becomes available. At present, there exist no validated, well-accepted models for
      benefit-risk assessment that have the appropriate degree of sophistication, and
      as a consequence no models are widely used by regulatory authorities or industry.
      The aim of the study was therefore to develop a new model for benefit-risk
      assessment of medicines using multi-criteria decision analysis (MCDA). METHODS:
      The MCDA methodology was used for a systematic approach to assess the benefit
      risk ratio of medicines. The reasons for adopting this approach were (1) taking
      multiple benefit and risk criteria into account, (2) making a judgement on the
      evidence and potential uncertainty because of the incompleteness of evidence, and
      (3) making trade-offs of the benefits against risks. RESULTS: It was demonstrated
      through a seven-step approach how MCDA is used to construct the model. Ten
      benefit and ten risk criteria were identified to form a value tree. Then fixed
      scales were established for all criteria and options on the criteria were scored.
      Weights were assigned for each criteria using swing-weighting. Finally
      sensitivity analysis was carried. CONCLUSIONS: This novel approach based on MCDA
      has the potential for being applied as a new tool for judging and deciding on the
      benefits and risks, thereby helping regulators and industry in the development
      and approval of new medicines and their adequate use.

PMID- 17546574
TI  - A quantitative approach to benefit-risk assessment of medicines - part 2: the
      practical application of a new model.
AB  - PURPOSE: Decisions leading to drug approval demand careful attention with respect
      to balancing benefits and risks. The new benefit-risk assessment model provides
      reassembling of the pieces of decision-making information using computer software
      to present a coherent overall picture for decision-makers. The aims of the study
      were to evaluate content validity of the new model and examine its practical
      application. METHODS: The expert panel (Annex 1) drawn from regulatory agencies
      in USA and Europe, academia and pharmaceutical industry, were encouraged to frank
      and open discussions about the way in which important, far-reaching decisions are
      taken within both companies and regulatory agencies and the potential
      shortcomings of such processes. The main component of the meeting was an
      interactive demonstration of the application of the technical model MCDA. The
      model was discussed using a hypothetical scenario based on safety and efficacy
      data relating to an atypical antipsychotic agent that was clinically tested
      against placebo and a comparator compound. RESULTS: The expert panel unanimously
      agreed that the methodology had great potential and it was recommended that it
      should be explored further as an adjunct to the decision-making process for both
      companies and regulatory agencies. An important part of this would be to
      undertake retrospective testing using actual case studies. CONCLUSIONS: The
      outcome of the workshop underpins practical utility of the new benefit-risk
      assessment MCDA model and provides evidence of its content validity. It is hoped
      that this encourages acceptability by regulatory agencies and the industry for
      its use in real scenarios.

PMID- 17546575
TI  - Interpreting clinically significant changes in patient-reported outcomes.
AB  - BACKGROUND: The goal of this study was to determine what magnitude of change in a
      patient-reported outcome score is clinically meaningful, so a clinicians' guide
      may be provided for estimating the minimal important difference (MID) when
      empiric estimates are not available. METHODS: Consecutive laryngeal cancer
      patients (n = 98) rated their quality of life (QOL) relative to other patients.
      These comparisons were contrasted with arithmetic differences in scores on the
      Functional Assessment of Cancer Therapy-Head and Neck (FACT-H&N) scale,
      Functional Assessment of Cancer Therapy-General (FACT-G) scale, 2 utility
      measures (the time tradeoff [TTO] and Daily Active Time Exchange [DATE]), and
      performance status (Karnofsky) scores. RESULTS: The FACT-H&N score needed to
      differ by 4% for average patients to rate themselves as "a little bit better"
      relative to other patients (95% CI, 1%-8%) and by 9% to rate themselves as "a
      little bit worse" relative to others (95% CI, 4%-13%). The corresponding values
      for other measures were FACT-G 4% (1%-7%) and 8% (95% CI, 5%-11%); TTO 5% (95%
      CI, 0%-11%) and 6% (95% CI, 0%-10%); DATE 5% (95%CI, 2%-9%) and 14% (95% CI, 0%
      5%); Karnofsky 4% (95% CI, 1%-6%) and 10% (95% CI, 7%-13%). In each case, the
      minimal important difference (MID) was about 5% to 10% of the instrument range.
      CONCLUSIONS. One rule of thumb for interpreting a difference in QOL scores is a
      benchmark of about 10% of the instrument range. Patients appear to be more
      sensitive to favorable differences, so an improvement of 5% may be meaningful.
      This simple benchmark may be useful as a rough guide to meaningful change.

PMID- 17546576
TI  - The geometric and electronic structure of a one-electron-oxidized nickel(II)
      bis(salicylidene)diamine complex.

PMID- 17546577
TI  - Total synthesis of (+)-azaspiracid-1. Part I: Synthesis of the fully elaborated
      ABCD aldehyde.

PMID- 17546578
TI  - Total synthesis of (+)-azaspiracid-1. Part II: synthesis of the EFGHI sulfone and
      completion of the synthesis.

PMID- 17546579
TI  - Silicon analogues of crown ethers and cryptands: a new chapter in host-guest
      chemistry?

PMID- 17546580
TI  - Drying droplets: a window into the behavior of nanorods at interfaces.

PMID- 17546581
TI  - One-dimensional, cofacial porphyrin polymers formed by self-assembly of meso
      tetrakis(ERE donor) zinc(II) porphyrins.
AB  - A series of meso-tetrakis-(ERE donor) zinc(II) porphyrins nZn (ERE donor = 4-R
      3,5-bis[(E)-methyl]phenyl; 1Zn: E = NMe2, R = Br; 2Zn: E = NMe2, R = H; 3Zn: E =
      OMe, R = Br; 4Zn: E = OMe, R = H) have been synthesized in excellent yields. As a
      result of the combination of a Lewis acidic site and eight Lewis basic sites
      within one molecule, monomeric molecules of nZn self-assemble to form one
      dimensional porphyrin polymers [nZn](infinity) in the solid state, as confirmed
      for 1Zn and 3Zn by X-ray crystallography. The coordination environment around the
      zinc(II) ions in these polymers is octahedral. They are ligated by four
      equatorial nitrogen atoms of the porphyrin and two apical E atoms (E = N, O)
      provided by the EBrE donor groups of adjacent nZn molecules. Complexes 2Zn and
      4Zn did not form single crystals, but solid-state UV/Vis analysis points to the
      formation of similar structures. Solution UV/Vis and 1H NMR spectroscopy
      indicated that interactions between 1Zn and 2Zn monomers in the polymers are
      stronger than between 3Zn and 4Zn monomers. Interestingly, they also revealed
      that the presence of a neighboring bromine atom in the EBrE donor groups has a
      considerable influence on the coordination properties of the benzylic N or O
      atoms. The zinc(II) ions of the porphyrins most likely adopt only
      hexacoordination in the solid state, owing to the unique predisposition of Lewis
      acidic and basic sites in the nZn molecules. Several parameters of the
      aggregates, for example, the interplanar separation between porphyrins and the
      zinc-zinc distances, change as a function of the coordinating E groups. The high
      degree of modularity in their synthesis makes these zinc(II) porphyrins an
      interesting new entry in noncovalent multiporphyrin assemblies.

PMID- 17546582
TI  - Persistent and remodeling hepatic preneoplastic lesions present differences in
      cell proliferation and apoptosis, as well as in p53, Bcl-2 and NF-kappaB
      pathways.
AB  - During rat hepatocarcinogenesis preneoplastic lesions (PNL) emerge which may
      persist (pPNL) and be sites of progress to cancer or suffer remodeling (rPNL)
      tending to disappear. Cellular and molecular mechanisms involved in both
      phenotypes are not sufficiently elucidated. pPNL and rPNL cellular proliferation
      and apoptosis were evaluated in rats submitted to the resistant hepatocyte (RH)
      model, and an adjusted growth index (AGI) was established. p53, Bcl-2, and NF
      kappaB p65 subunit expression was evaluated by immunohistochemistry in pPNL and
      rPNL. p65 expression and NF-kappaB activation was evaluated by Western blot
      assays in whole livers. A lower number of BrdU-stained hepatocyte nuclei/mm(2)
      and higher number of apoptotic bodies (AB) per mm(2) were observed in remodeling
      compared to pPNL. Cytoplasmic p53 accumulation is related to increased
      hepatocarcinoma malignancy. We observed that 71.3% pPNL and 25.4% rPNL (P < 0.05)
      presented p53 staining in the cytoplasm. Similarly, 67.7% pPNL and 23.1 % rPNL (P
      < 0.05) presented increased Bcl-2 staining. Thirty-two percent pPNL and 15.6%
      rPNL (P < 0.05) presented p65 staining. Compared to normal rats, increase (P <
      0.05) of hepatic p65 expression and NF-kappaB activation in rats submitted to the
      RH model was observed. In agreement to previous studies hepatic pPNL and rPNL
      differ regarding cell proliferation and apoptosis. Moreover, persistence and
      remodeling involve differences in p53, Bcl-2, and NF-kappaB pathways. These data
      point to molecular pathways that may direct preneoplastic lesions to
      spontaneously regress or to progress to cancer. J. Cell. Biochem. 103: 538-546,
      2008. (c) 2007 Wiley-Liss, Inc.

PMID- 17546583
TI  - Diapause disruption with tebufenozide for early-instar control of the spruce
      budworm, Choristoneura fumiferana.
AB  - In North America, the eastern spruce budworm, Choristoneura fumiferana Clem., is
      an important coniferous pest against which tebufenozide has proven effective as a
      control product. By acting as an ecdysone agonist, tebufenozide can induce
      precocious moulting in late (fifth-sixth) instars but can also be carried over to
      the next generation owing to its persistence on foliage. The authors conducted
      laboratory experiments on first-instar larvae treated with tebufenozide dissolved
      in acetone. Larvae exposed to doses equal to or above 0.1 microg cm(-2) displayed
      precocious moulting in the second instar after hibernaculum spinning, which
      effectively disrupted diapause. Larger doses induced moulting in first instars.
      Evidence is provided that this dose-response difference is related to whether or
      not an effective dose of tebufenozide is ingested by the first instar prior to
      the peak of moulting hormone (20-hydroxyecdysone) in first instars. Doses
      ineffective to kill first instars are carried over to the second instar, where
      they induce a precocious moult. This type of response to tebufenozide is
      dependent on the presence of a moulting machinery (the EcR-USP receptor complex)
      that is ready for ecdysone transduction. Interestingly, ecdysone levels are low
      in second instars, as measured by a radioimmunoassay, which suggests that
      diapause in spruce budworm is maintained by a suppression of ecdysone production.
      Thus, diapause disruption by tebufenozide may well provide an alternative control
      strategy for this important pest.

PMID- 17546584
TI  - Effects of follicle size and stages of maturation on mRNA expression in bovine in
      vitro matured oocytes.
AB  - Transcription in bovine oocytes: The goal of this study was to unravel the
      dynamics of transcripts thought to be critically involved in oocyte maturation.
      The relative abundance (RA) of DYNLL1 (cytoplasmic dynein light chain LC8),
      DYNC1I1 (cytoplasmic dynein 1 intermediate chain), DCTN1 (dynactin 1; pGlued
      homolog, the activator of the cytoplasmic dynein complex 1), PMSB1 (proteasome
      beta subunit 1), PMSA4 (proteasome alfa subunit 4), PAP (poly-A polymerase) and
      Cx43 (connexin 43) were determined by semi-quantitative endpoint RT-PCR at
      different stages of IVM, that is, GV, GVBD, MI and MII in oocytes collected from
      follicles of two different size categories, that is, <2 mm and 2-8 mm. The RA of
      DYNLL1 and DYNC1I1 were significantly higher in immature oocytes from bigger
      follicles than in oocytes from small follicles. Messenger RNA expression levels
      were similar for DCTN1, PMSB1, PMSA4, PAP, and Cx43 in the two groups during the
      maturation process. RA of DYNLL1, DYNC1I1 and PMSB1 decreased significantly
      during IVM in oocytes from follicles 2 to 8 mm. The RA for DYNLL1 was
      significantly higher in GVBD and MI in the oocytes from follicles 2 to 8 mm in
      size compared to the other group. The higher mRNA expression of DYNLL1 and
      DYNC1I1 and the diverging dynamics of DYNLL1, DYNC1I1, and PMSB1 mRNA expression
      during IVM in oocytes from the different follicle categories could be related to
      the developmental capacity, that is, development to blastocysts after IVF. The
      differences found between groups of oocytes could serve as a marker to assess the
      developmental capacity of bovine oocytes.

PMID- 17546585
TI  - Mechanotransduction from the ECM to the genome: are the pieces now in place?
AB  - A multitude of biochemical signaling processes have been characterized that
      affect gene expression and cellular activity. However, living cells often need to
      integrate biochemical signals with mechanical information from their
      microenvironment as they respond. In fact, the signals received by shape alone
      can dictate cell fate. This mechanotrasduction of information is powerful,
      eliciting proliferation, differentiation, or apoptosis in a manner dependent upon
      the extent of physical deformation. The cells internal "prestressed" structure
      and its "hardwired" interaction with the extra-cellular matrix (ECM) appear to
      confer this ability to filter biochemical signals and decide between divergent
      cell functions influenced by the nature of signals from the mechanical
      environment. In some instances mechanical signaling through the tissue
      microenvironment has been shown to be dominant over genomic defects, imparting a
      normal phenotype on cells that otherwise have transforming genetic lesions. This
      mechanical control of phenotype is postulated to have a central role in
      embryogenesis, tissue physiology as well as the pathology of a wide variety of
      diseases, including cancer. We will briefly review studies showing physical
      continuity between the external cellular microenvironment and the interior of the
      cell nucleus. Newly characterized structures, termed nuclear envelope lamina
      spanning complexes (NELSC), and their interactions will be described as part of a
      model for mechanical transduction of extracellular cues from the ECM to the
      genome.

PMID- 17546586
TI  - Comparison of RNA amplification methods and chip platforms for microarray
      analysis of samples processed by laser capture microdissection.
AB  - Laser capture microdissection (LCM) permits isolation of pure cell populations
      from which RNA can be extracted, amplified, and subjected to microarray analysis,
      allowing information to be obtained on the gene expression profile of defined
      cell types. To avoid amplification artifacts and detect genes expressed at
      different levels, it is important to optimize the choice of both RNA
      amplification step and microarray platform. We captured by LCM the same colon
      cancer biopsy and conducted a cross comparison of distinct RNA amplification
      methods and different chip platforms. We tested two RNA amplification methods
      with different chemistry: the one-cycle Ovation system (NuGEN) and the two-cycle
      Ribo OA method (Arcturus). We also compared two different whole genome platforms,
      based on Affymetrix technology: the U133 plus 2.0 and the X3P array, with probe
      sets closer to the 3' end of transcripts. After RNA amplification, microarray
      analysis, and data normalization, we investigated reproducibility and correlation
      of different methods and arrays. Our results indicate that the Arcturus Ribo OA
      method is superior for both array choices, especially in combination with X3P
      arrays, showing the lowest variance and Spearman correlation of 0.986. The
      quicker NuGEN procedure, when coupled with X3P arrays, also yielded excellent
      results (correlation of 0.951). These observations will be useful for planning
      large-scale analyses of LCM-dissected clinical samples.

PMID- 17546587
TI  - Novel hormone "receptors".
AB  - Our concepts of hormone receptors have, until recently, been narrowly defined. In
      the last few years, an increasing number of reports identify novel proteins, such
      as enzymes, acting as receptors. In this review we cover the novel receptors for
      the hormones atrial naturetic hormone, enterostatin, hepcidin, thyroid hormones,
      estradiol, progesterone, and the vitamin D metabolites 1,25(OH)(2)D(3) and
      24,25(OH)(2)D(3).

PMID- 17546589
TI  - Overexpression of ErbB2 in the exocrine pancreas induces an inflammatory response
      but not increased proliferation.
AB  - Tyrosine kinase receptors such as members of the epidermal growth factor receptor
      family and their respective ligands are frequently overexpressed in pancreatic
      cancer as well as in chronic pancreatitis. In this study, the role of ErbB2 in
      the exocrine pancreas was examined by ectopic overexpression under the control of
      the proximal rat elastase promoter. Three independent transgenic mouse lines
      overexpressing ErbB2 were established by pronuclear injection. Pancreatic mRNA
      and protein levels were analyzed by real time PCR, immunohistochemistry and
      immunoblot analysis, RAS activity by using a specific immunoprecipitation assay
      and various kinase activities by phosphospecific antibodies. Overexpression of
      ErbB2 in the exocrine pancreas resulted in increased RAS activity and downstream
      activation of ERK1/2, but not in transgenic increased proliferation of acinar and
      ductal cells. At later timepoints, some mice showed focal areas of acinar cell
      damage with upregulated mRNA levels for Cyclin D1 and p16(INK4a). Despite the
      increased mRNA level, cyclin D1 protein levels were downregulated. We observed
      areas of focal infiltrations with inflammatory cells interspersed in the exocrine
      pancreas. NF-kappaB activity was induced in transgenic acinar cells compared with
      controls contributing to high levels of chemokine and cytokine gene expression
      such as CCR-1 and CCL3. These data suggest that overexpression of ErbB2 in acinar
      cells leads to increased RAS activity without cell cycle progression and mediates
      inflammation via NF-kappaB. We conclude that the biological response of ErbB2/RAS
      signaling depends highly on cellular context.

PMID- 17546590
TI  - Novel approach for detecting global epigenetic alterations associated with tumor
      cell aneuploidy.
AB  - Although aneuploidy is commonly observed in human cancers, the molecular
      mechanism underlying aneuploidization remains unclear. We used multiploid cancer
      model that had diploid and aneuploid cancer cells within the same cancerous
      tissue and attempted to detect specific epigenetic alterations associated with
      tumor cell aneuploidy. Thirty-four multiploid colorectal cancers were subjected
      to crypt isolation and cell sorting, and paired diploid and aneuploid cancer
      cells were separated from each cancerous tissue. A methylated CpG island
      amplification provided a considerable number of CpG sequences that showed
      different methylation status between the above 2 cell populations. BLAST homology
      search revealed 24 different candidates (11 hypermethylated and 13
      hypomethylated) from these sequences. The putative promoter sequence of the SALL4
      (sal-like 4, a human homolog to Drosophila spalt) gene was particularly more
      frequently hypermethylated in aneuploid cells (62%) than diploid ones (35%) in
      the 34 multiploid cancers. Moreover, such hypermethylation occurred more often in
      aneuploid cancers (8 of 16, 50%) than diploid cancers (3 of 18, 17%). In
      combination with demethylation study on cultured cells, these results implied a
      possible association between epigenetic silencing of SALL4 and tumor cell
      aneuploidy. SALL4 may be one of important key players that act as "caretakers"
      for chromosomal stability. Our new approach is a powerful tool for the global
      identification of such key players.

PMID- 17546591
TI  - Expression of an endogenous retroviral sequence from the HERV-H group in
      gastrointestinal cancers.
AB  - Human endogenous retroviruses (HERVs) account for approximately 8% of the human
      genome. Since the majority of HERV elements have accumulated inactivating
      mutations in the viral genes, only few expressed viral open reading frames (ORFs)
      have been described. In this study, we have analyzed the expression of a HERV-H
      copy located on Xp22.3 encompassing a potential ORF immediately downstream of the
      viral promoter. Conventional and real time RT-PCR based expression analysis of
      this specific HERV-H sequence showed overexpression in 16 of 34 (47%) colorectal,
      25 of 63 (40%) gastric and 2 of 12 (17%) pancreatic cancers, whereas no
      overexpression was detected in bronchial and cervical cancers. Normal human
      testis, placenta and breast tissue did not show expression of this sequence. CpG
      methylation analysis of the viral promoter revealed a loss of methylation in cell
      lines expressing the HERV-H sequence as compared to nonexpressing cell lines and
      lymphocyte DNA derived from healthy individuals. Further investigations of the
      HERV-H long terminal repeat and the HERV-H RNA are necessary to assess the
      functional relevance of the HERV-H expression.

PMID- 17546592
TI  - Survival of squamous cell carcinoma of the head and neck in relation to human
      papillomavirus infection: review and meta-analysis.
AB  - Human papillomavirus (HPV) has been associated with head and neck squamous cell
      carcinomas (HNSCC), especially of the oropharynx, with highest distribution in
      the tonsils. HPV infection has been associated with improved outcome, although
      not all the studies show consistent results. The reason for this is not clear. We
      reviewed all published articles and conducted a meta-analysis on the overall
      relationship between HPV infection and overall survival (OS) and disease-free
      survival (DFS) in HNSCC. Patients with HPV-positive HNSCC had a lower risk of
      dying (meta HR: 0.85, 95% CI: 0.7-1.0), and a lower risk of recurrence (meta HR:
      0.62, 95%CI: 0.5-0.8) than HPV-negative HNSCC patients. Site-specific analyses
      show that patients with HPV-positive oropharyngeal tumours had a 28% reduced risk
      of death (meta HR: 0.72, 95%CI: 0.5-1.0) in comparison to patients with HPV
      negative oropharyngeal tumours. Similar observations were made for DFS (meta HR:
      0.51, 95% CI: 0.4-0.7). There was no difference in OS between HPV-positive and
      negative non-oropharyngeal patients. The observed improved OS and DFS for HPV
      positive HNSCC patients is specific to the oropharynx; these tumours may have a
      distinct etiology from those tumours in non-oropharyngeal sites.

PMID- 17546593
TI  - Mutations of the PIK3CA gene in hereditary colorectal cancers.
AB  - Somatic mutations of the PIK3CA gene have recently been detected in various human
      cancers, including sporadic colorectal cancer. However, mutations of the PIK3CA
      gene in hereditary colorectal cancers have not been clarified. To elucidate the
      mutation status in familial adenomatous polyposis (FAP) and hereditary
      nonpolyposis colorectal cancer (HNPCC), which are the most common hereditary
      colorectal cancers, we investigated PIK3CA mutations in 163 colorectal tumors,
      including adenomas, intramucosal carcinomas and invasive carcinomas. For
      comparison, we also analyzed mutations of the same gene in 160 sporadic
      colorectal tumors at various histopathological stages. Analysis at exons 1, 7, 9
      and 20 of the PIK3CA gene revealed somatic mutations in 21% (8 of 39) of FAP
      invasive carcinomas, 21% (7 of 34) of HNPCC invasive carcinomas, 15% (8 of 52) of
      sporadic invasive carcinomas, and 14% (7 of 50) of sporadic colorectal metastases
      in the liver. Mutations in FAP and HNPCC carcinomas predominantly occurred in the
      kinase domain (exon 20), while the majority of mutations in sporadic cases
      occurred in the helical domain (exon 9). Adenomas and intramucosal carcinomas
      from all patients exhibited no mutations (0 of 148). Our data suggest that PIK3CA
      mutations contribute to the invasion step from intramucosal carcinoma to invasive
      carcinoma in colorectal carcinogenesis in FAP and HNPCC patients at a similar
      extent to that seen in sporadic patients.

PMID- 17546594
TI  - P53 codon 72 polymorphism and gastric cancer: a meta-analysis of the literature.
AB  - Studies investigating the association between p53 codon 72 polymorphism and
      gastric cancer risk report conflicting results. The objective of this study was
      to quantitatively summarize the evidence for such a relationship. Two
      investigators independently searched the Medline and Embase databases. This meta
      analysis included 12 case-control studies, which included 1,665 gastric cancer
      cases and 2,358 controls. The combined results based on all studies showed that
      there was no significant difference in genotype distribution [Arg/Arg odds ratio
      (OR) = 0.96, 95% confidence interval (CI) = 0.79, 1.16; Pro/Pro (OR = 1.21, 95%
      CI = 0.92, 1.58); Pro/Arg (OR = 0.95, 95% CI = 0.79, 1.14)] between gastric
      cancer and noncancer patients. When stratifying for race, results were similar
      except that patients with gastric cancer had a significantly lower frequency of
      Arg/Arg (OR = 0.84, 95% CI = 0.72, 0.99) than noncancer patients among Asians.
      Stratified the various studies by the location, stage, Lauren's classification,
      and histological differentiation of gastric cancer, we found that (i) patients
      with cardia gastric cancer had a significantly higher frequency of Pro/Pro (OR =
      3.20, 95% CI = 1.46,7.01) than those with noncardia gastric cancer among Asians;
      (ii) patients with advanced (stage III/IV) gastric cancer had a significantly
      higher frequency of Arg/Arg (OR = 1.48, 95% CI = 1.01, 2.16) than those with
      early (stage I/II) gastric cancer among Asians; (iii) patients with poor
      differentiation had a significantly lower frequency of Pro/Pro (OR = 0.13, 95% CI
      = 0.03, 0.64) than those with well differentiation among Caucasians. This meta
      analysis suggests that the p53 codon 72 polymorphism may be associated with
      gastric cancer among Asians, and that difference in genotype distribution may be
      associated with the location, stage, and histological differentiation of gastric
      cancer.

PMID- 17546595
TI  - Sperm binding properties and secretory activity of the bovine oviduct immediately
      before and after ovulation.
AB  - The possibility that differences in hormonal regimes between the two oviducts in
      the cow around ovulation affects secretory activity of the oviduct epithelial
      cells and/or sperm-oviduct binding was studied. Oviducts were collected
      immediately after slaughter at 6 hr before to 5 hr after timed ovulation of 14
      normally cyclic cows that had been inseminated (n = 6) or not (n = 8) and
      material obtained from the same cows was processed in three ways. First, in vivo,
      after artificial insemination of the cows, low numbers of sperm cells (approx. 15
      per oviduct) were found within the entire oviducts as observed by scanning
      electron microscopy (SEM). Almost all sperm were located in the isthmus and then
      only on ciliated cells and showed without exception fully matured, intact
      morphology. Secretory activity of noninseminated oviduct epithelia was induced
      after ovulation which was most predominant in the pockets of the ipsi-lateral
      ampulla compared to the contra-lateral ampulla (P < 0.01). Second, ex vivo,
      explants dissected from oviducts of the noniseminated cows were incubated with
      sperm. In all cases, the sperm bound to the explants in a similar pattern as
      observed in vivo and this binding was strictly fucose-dependent. The main
      difference with in vivo experiments was the high numbers of sperm bound at any
      site of the oviduct ( approximately 3,000 cells per mm(2)) indicating the high
      sperm binding capacity of the oviduct epithelia. Ovulation induced a striking
      drop in sperm binding capacity in the oviducts and was most pronounced in the
      isthmus ( approximately 1,300 cells per mm(2); P < 0.001) and to a lesser extent
      in the ampulla ( approximately 2,000 cells per mm(2), P < 0.01). Third, in vitro,
      pieces of tissue dissected from oviducts of the noninseminated cows were cultured
      to mono-layers. Culturing epithelial cells resulted in loss of their normal
      morphological appearance. In all cases, the sperm binding capacity in monolayers
      was very low (<50 cells per mm(2)) when compared to corresponding explants (P <
      0.0001). Sperm binding to monolayers originating from the isthmus (<25 cells per
      mm(2)) was lower than in those from the ampulla (40-50 cells per mm(2); P < 0.01)
      and remained similar after ovulation. In all three approaches, no significant
      differences were found in sperm-oviduct binding characteristics and sperm
      distribution in the ipsi- versus contra-lateral oviducts. This indicates, that
      systemic endocrine changes around ovulation rather than specific oviduct changes
      at the ipsi-lateral oviduct induce secretion in oviduct epithelial cells, and
      thus induce sperm release.

PMID- 17546596
TI  - Reduced numbers of IL-7 receptor (CD127) expressing immune cells and IL-7
      signaling defects in peripheral blood from patients with breast cancer.
AB  - Interleukin-7-receptor-signaling plays a pivotal role in T-cell development and
      maintenance of T-cell memory. We studied IL-7Ralpha (CD127) expression in PBMCs
      obtained from patients with breast cancer and examined IL-7 receptor-mediated
      downstream effects defined by STAT5 phosphorylation (p-STAT5). Reduced numbers of
      IL-7Ralpha-positive cells were identified in CD4+ T-cells as well as in a CD8+ T
      cell subset defined by CD8alpha/alpha homodimer expression in patients with
      breast cancer. PBMCs obtained from healthy donors (n = 19) and from patients with
      breast cancer (n = 19) exhibited constitutive p-STAT5 expression in the range of
      0-6.4% in CD4+ T-cells and 0-4% in CD8+ T-cells. Stimulation with recombinant
      human IL-7 for 15 min increased p-STAT5 expression up to 36-97% in CD4+T-cells
      and to 26-90% in CD8+T-cells obtained from healthy control donors (n = 19). In
      contrast, PBMCs obtained from 13/19 patients with breast cancer did not respond
      to IL-7 as defined by STAT5 phosphorylation, despite expression of IL-7Ralpha on
      T-lymphocytes. T-cells were further characterized for IL- 2 and IFN-gamma
      production induced by PMA/Ionomycin. PBMCs from 9/19 patients with breast cancer
      showed decreased IL-2 and IFN-gamma production combined with IL-7-signaling
      defects; PBMCs from 4 patients with breast cancer exhibited deficient IL-7
      signaling, yet intact cytokine production. Reduced numbers of IL-7Ralpha-positive
      cells and nonresponsiveness to IL-7, defined by lack of STAT5 phosphorylation,
      characterizes the immunological profile in T-cells from patients with breast
      cancer.

PMID- 17546597
TI  - Epstein-Barr virus latent membrane protein 1 promotes concentration in
      multivesicular bodies of fibroblast growth factor 2 and its release through
      exosomes.
AB  - FGF-2, a potent angiogenic factor that is involved in tumor invasion, is known to
      be released extracellularly by a nonclassical secretory pathway. Recently it has
      become clear that Epstein-Barr virus, specifically its oncoprotein LMP1, can
      induce expression of angiogenic factors. Among these factors is FGF-2. LMP1 not
      only promotes expression of FGF-2, but also the release extracellularly of its 18
      kDa isoform. We analyzed the mechanism of FGF-2 release induced by LMP1. Confocal
      immunofluorescence microscopy revealed colocalization of FGF-2 with LMP1 in small
      dots also stained positively for CD63 and cathepsin D, markers of late endosomes
      or multivesicular bodies. Biochemical analysis and immunoelectron microscopy of
      purified exosomal fractions from cotransfected cells demonstrated increased
      release of exosomes and the concentration of LMP1 and FGF-2 in these structures.
      Moreover, cotransfection appeared to induce partial redistribution of the
      Na(+)/K(+)-ATPase, which participates in FGF-2 release, from the plasma membrane
      to the intracellular LMP1/FGF-2 positive dots. Treatment with ouabain, which
      inhibits Na(+)/K(+)-ATPase activity, partially suppressed FGF-2 secretion via
      exosomes in a dose-dependent manner. The results suggest that exosomes may
      represent a previously unrecognized mechanism for FGF-2 release mediated by LMP1,
      and that this pathway involves the activity of Na(+)/K(+)-ATPase.

PMID- 17546598
TI  - Gene therapy using ets-1 transcription factor decoy for peritoneal dissemination
      of gastric cancer.
AB  - The ets-1 transcription factor plays an important role in cell proliferation,
      differentiation, apoptosis and tissue remodeling. Aberrant ets-1 expression
      correlates with aggressive tumor behavior and poorer prognosis in patients with
      various malignancies. This study evaluated the efficacy of double-stranded decoy
      oligonucleotides targeting ets-1-binding cis elements for the suppression of ets
      1 in treatment of a peritoneal dissemination model of gastric cancer. In vitro,
      MTT assay was performed to evaluate the effect of the ets-1 decoy on cell growth.
      Electrophoretic mobility shift assay (EMSA) was performed to determine ets-1
      activity. In vivo, the effect of the ets-1 decoy was investigated in the
      peritoneal dissemination nude mice model. Disseminated nodules were analyzed
      immunohistochemically. Ets-1 decoy, but not scrambled decoy, significantly
      inhibited cell growth in 2 gastric cancer cell lines, which showed overexpression
      of ets-1 protein by inhibiting the binding activity of ets-1. In the peritoneal
      dissemination model, the ets-1 decoy significantly suppressed the disseminated
      nodules, and tended to prolong the survival rate. PCNA index, microvessel density
      and VEGF expression were also reduced in peritoneal tumors treated with ets-1
      decoy. Intraperitoneal injection of ets-1 decoy inhibited peritoneal
      dissemination of gastric cancer in a nude mice model. The results indicate that
      the decoy strategy for ets-1 offers a promising therapy for patients with
      incurable peritoneal dissemination of gastric cancer, most of which show
      overexpression of ets-1 protein.

PMID- 17546599
TI  - Targeting the IGF-1R using picropodophyllin in the therapeutical 5T2MM mouse
      model of multiple myeloma: beneficial effects on tumor growth, angiogenesis, bone
      disease and survival.
AB  - During the last decade, a central role for insulin-like growth factor 1 (IGF-1)
      in the pathophysiology of multiple myeloma (MM) has been well established. IGF-I
      provided by the tumor-microenvironment interaction may directly and indirectly
      facilitate the migration, survival and expansion of the MM cells in the bone
      marrow (BM). The inhibition of the IGF-1R-mediated signaling pathway has recently
      been suggested to be a possible new therapeutic principle in MM. Using the mouse
      5T2MM model, we now demonstrate that targeting the IGF-1R using picropodophyllin
      (PPP) in a therapeutical setting not only has strong antitumor activity on the
      established MM tumor but also influences the BM microenvironment by inhibiting
      angiogenesis and bone disease, having a profound effect on the survival of the
      mice. At therapeutically achievable concentrations of PPP, the average survival
      was 180 days for the PPP-treated mice as compared to 100 days for vehicle-treated
      mice. PPP used as single drug treatment in the 5T2MM model resulted in a decrease
      of tumor burden by 65% while the paraprotein concentrations were reduced by 75%.
      This decrease was associated with a significant inhibition of tumor-associated
      angiogenesis and osteolysis. The present studies on the biological effects of PPP
      in the 5T2MM model constitute an important experimental platform for future
      therapeutic implementation.

PMID- 17546600
TI  - Improvement of hyperlipidemia by indomethacin in Min mice.
AB  - Apc gene-deficient Min and Apc(1309) mice feature a hyperlipidemic state with a
      markedly low expression level of lipoprotein lipase (LPL) compared to their wild
      type counterparts. We previously showed that induction of LPL mRNA by peroxisome
      proliferator-activated receptor (PPAR) alpha and gamma agonists or an LPL
      selective inducer suppresses both high serum lipid levels and intestinal polyp
      formation in these model animals. Since the general cyclooxygenase inhibitor,
      indomethacin, is known to suppress intestinal tumor development, but not to
      affect serum lipids, its influence in Min mice was here investigated. Treatment
      with 2.5, 5 and 10 ppm indomethacin in the diet for 14 weeks from 6 weeks of age
      caused significant dose-dependent reduction in serum triglycerides, along with a
      reduction in the numbers of intestinal polyps to 25% of the untreated control
      value. LPL mRNA levels in the liver were slightly increased by indomethacin
      treatment. We further performed oligonucleotide microarray analysis and
      quantitative PCR analysis and found 8 lipid metabolism-related genes, regulated
      by sterol regulatory element binding protein-1c, to be modulated by indomethacin
      treatment in the Min mouse liver. Furthermore, TNFalpha was downregulated. These
      results indicate that indomethacin might suppress intestinal tumor formation
      together with a hyperlipidemic state by regulating LPL and other lipid metabolic
      factors.

PMID- 17546601
TI  - Use of a novel 3D culture model to elucidate the role of mesothelial cells,
      fibroblasts and extra-cellular matrices on adhesion and invasion of ovarian
      cancer cells to the omentum.
AB  - The omentum is a major site of ovarian cancer metastasis. Our goal was to
      establish a three-dimensional (3D) model of the key components of the omental
      microenvironment (mesothelial cells, fibroblasts and extracellular matrices) to
      study ovarian cancer cell adhesion and invasion. The 3D model comprised of
      primary human fibroblasts extracted from normal human omentum, mixed with ECM and
      covered by a layer of primary human mesothelial cells, also from normal human
      omentum. After addition of ovarian cancer cells, the histological appearance of
      the 3D culture mimicked microscopic metastases to the omentum from patients with
      ovarian cancer. When ovarian cancer cells, SKOV3ip.1 and HeyA8, were applied to
      the 3D omental culture, 60% and 68% of all cells attached, respectively, but only
      18% and 25% were able to invade. Ovarian cancer cells preferentially adhered to
      and invaded collagen I, followed by binding to collagen IV, fibronectin,
      vitronectin, laminin 10 and 1. Omental mesothelial cells significantly inhibited
      ovarian cancer cell adhesion and invasion, while omental fibroblasts induced
      adhesion and invasion. This effect is clearly mediated by direct cell-cell
      contact, since conditioned medium from mesothelial cells or fibroblasts has a
      minimal, or no, effect on ovarian cancer cell adhesion and invasion. In summary,
      we have established a 3D model to study the early steps of ovarian cancer
      metastasis to the human omentum, and found that omental mesothelial cells
      inhibit, while omental fibroblasts and the ECM enhance, the attachment and
      invasion of ovarian cancer cells.

PMID- 17546602
TI  - Cross-talk between Wnt signaling pathways in human mesenchymal stem cells leads
      to functional antagonism during osteogenic differentiation.
AB  - Wnt signaling is involved in developmental processes and in adult stem cell
      homeostasis. This study analyzes the role(s) of key Wnt signaling mediators in
      the maintenance and osteogenesis of mesenchymal stem cells (MSCs). We focus
      specifically on the involvement of low-density lipoprotein-related protein 5
      (LRP5), T-cell factor 1 (TCF1), and Frizzled (Fz) receptors, in the presence or
      absence of exogenous, prototypical canonical (Wnt3a), and non-canonical (Wnt5a)
      Wnts. In undifferentiated MSCs, LRP5 and TCF1 mediate canonical Wnt signal
      transduction, leading to increased proliferation, enhanced synergistically by
      Wnt3a. However, LRP5 overexpression inhibits osteogenic differentiation, further
      suppressed by Wnt3a. Wnt5a does not affect cell proliferation but enhances
      osteogenesis of MSCs. Interestingly, Wnt5a inhibits Wnt3a effects on MSCs, while
      Wnt3a suppresses Wnt5a-mediated enhancement of osteogenesis. Flow cytometry
      revealed that LRP5 expression elicits differential changes in Fz receptor
      profiles in undifferentiated versus osteogenic MSCs. Taken together, these
      results suggest that Wnt signaling crosstalk and functional antagonism with the
      LRP5 co-receptor are key signaling regulators of MSC maintenance and
      differentiation.

PMID- 17546603
TI  - Effects of tyroserleutide on gene expression of calmodulin and PI3K in
      hepatocellular carcinoma.
AB  - Tyroserleutide (YSL) is a tripeptide compound that has exhibited inhibitory
      effects on hepatocellular carcinoma in our previous research. The mechanism of
      this antitumor activity involves the second messenger, Ca(2+). Ca(2+) influences
      cell function through the Ca(2+)/calmodulin (CaM) pathway, and abnormality of the
      Ca(2+)/CaM system correlates closely with the occurrence of tumors. In addition,
      CaM associates with phosphatidylinositol 3 kinase (PI3K), thereby enhancing the
      activity of PI3K, which promotes cell proliferation. In order to investigate its
      anti-tumor mechanism, we studied the effects of YSL on CaM protein expression and
      mRNA level, PI3K activity, PI3K regulatory subunit p85 protein expression and
      mRNA level, and the mRNA level of PI3K catalytic subunits p110alpha and p110gamma
      in human hepatocellular carcinoma BEL-7402 xenograft tumors in nude mice. Our
      results showed that YSL decreased the mRNA level and protein expression of CaM,
      inhibited the activity of PI3K, and reduced the mRNA level and protein expression
      of the PI3K regulatory subunit p85 and mRNA level of PI3K catalytic subunits
      p110alpha and p110gamma. Accordingly, it is suggestive that the anti-tumor
      effects of YSL may be mediated by down regulation of CaM and PI3K subunits p85
      and p110, influencing the signal transduction pathway in the tumor cells and
      perhaps overcoming the dysfunctional PI3K activity in tumors.

PMID- 17546604
TI  - A novel role for Bcl-2 associated-athanogene-1 (Bag-1) in regulation of the
      endoplasmic reticulum stress response in mammalian chondrocytes.
AB  - BAG-1 (Bcl-2 associated athanogene-1) is a multifunctional protein, linking cell
      proliferation, cell death, protein folding, and cell stress. In vivo, BAG-1 is
      expressed in growth plate and articular cartilage, and the expression of BAG-1 is
      decreased with aging. Chondrocytes respond to endoplasmic reticulum (ER) stress
      with decreased expression of extracellular matrix proteins, and prolonged ER
      stress leads to chondrocyte apoptosis. Here we demonstrate for the first time
      that BAG-1 is involved in ER stress-induced apoptosis in chondrocytes. Induction
      of ER stress through multiple mechanisms all resulted in downregulation of BAG-1
      expression. In addition, direct suppression of BAG-1 expression resulted in
      chondrocyte growth arrest and apoptosis, while stable overexpression of BAG-1
      delayed the onset of ER stress-mediated apoptosis. In addition to regulating
      apoptosis, we also observed decreased expression of collagen type II in BAG-1
      deficient chondrocytes. In contrast, overexpression of BAG-1 resulted in
      increased expression of collagen type II. Moreover, under ER stress conditions,
      the reduced expression of collagen type II was delayed in chondrocytes
      overexpressing BAG-1. These results suggest a novel role for BAG-1 in supporting
      viability and matrix expression of chondrocytes.

PMID- 17546605
TI  - Prenatal diagnosis of Marfan syndrome.

PMID- 17546606
TI  - Selected anthropometric measurements of Akwesasne Mohawk youth: skinfolds,
      circumferences, and breadths.
AB  - Nationally, Native American youth have been shown to be at risk for overweight,
      and an increased prevalence of obesity among Native American children has been
      consistently reported. We describe skinfolds, circumferences, and body breadths
      to assess body size and shape of Akwesasne Mohawk youth (n = 271) between the
      ages of 10.0 and 16.99. Akwesasne is a sovereign nation with territory in New
      York state and Canada. Sex- and age-specific comparisons were made to reference
      values published from the Advance Data from Vital and Health Statistics and from
      the Third National Health and Examination Survey (NHANES III). Akwesasne youth
      have thicker skinfolds and larger circumferences than youth in the national
      surveys. Additionally, these cross-sectional data indicate that body fat is more
      centrally distributed in Akwesasne Mohawk boys and girls. Given the numerous
      studies emphasizing the importance of body fat distribution as a risk factor for
      chronic, obesity-related diseases prevalent within Native American communities,
      and the high level of fatness presented in this study, more concerted efforts
      need to be applied to help reduce the development of overweight in children from
      an early age.

PMID- 17546607
TI  - Longitudinal relationships between nutritional status, body composition, and
      physical fitness in rural children of South Africa: The Ellisras longitudinal
      study.
AB  - The objective of this study was to investigate the development and tracking of
      nutritional status, body composition and physical fitness, and the longitudinal
      relationship of changes in nutritional status, and body composition with changes
      in physical fitness over a 1-year period of follow-up. Studied were 380 boys and
      322 girls aged 7-14 years from the Ellisras Longitudinal Study. Boys and girls
      were divided into two groups of pre-adolescence (<11 years) and adolescence (>10
      years). High tracking coefficients (>8) were found for nutritional status, body
      mass index, and fat-free mass, while low tracking coefficients (<4) were found
      for the sum of skinfolds, fat mass, arm muscle area, and central fat
      distribution. Moderate and low tracking coefficients were found for the physical
      fitness items. Longitudinal regression analyses showed that physical fitness
      performances that require a high energy flux over a short period of time are
      affected by muscle wasting, whereas having a low body weight appears to be
      important for a good performance on other fitness items in these malnourished
      rural South African children.

PMID- 17546608
TI  - Polymorphic Alu insertions in five North-West Italian populations.
AB  - We analyzed the frequencies of eight human polymorphic Alu insertion loci in
      population samples from five towns in North-West Italy: Postua, Cavaglia, Biella,
      Torino, and Genova. All loci under scrutiny were found to be polymorphic in all
      samples, with the two exceptions of locus A25 in Postua, which was fixed for the
      absence of the Alu element, and APO in Genova, where the Alu insertion was fixed.
      Heterozigosity values were highly variable in all loci. F(ST) values for all loci
      indicate that most of the variability is found within populations, while between
      population variability is lower. In the multidimensional scaling (MDS) analysis
      plot, the studied populations are separated from the main group represented by
      European populations. The Postua sample is set apart also from neighboring towns
      as Cavaglia and Biella, confirming previous observations of the demographic
      isolation of this population.

PMID- 17546610
TI  - The stem cell hypothesis in head and neck cancer.
AB  - Cancer stem cells (CSCs) are tumoral cells which have stem features such as self
      renewal, high migration capacity, drug resistance, high proliferation abilities.
      In the last 10 years the pathological meaning and the existence of CSCs have been
      matter of discussion and a large number of articles have been published about the
      role that these cells play in the development and maintenance of the tumors. Head
      and neck squamous-cell carcinoma (HNSCC) is the sixth most common cancer
      worldwide: early diagnosis of high-risk premalignant lesions are high priorities
      for reducing deaths due to head and neck cancer. In the last years the CSCs
      hypothesis has been faced also for head and neck cancer, with the aim of a better
      comprehension of the tumor biology and an early diagnosis. The evidence that the
      development of a tumor comes from a small number of cells with stem-like
      characteristic, could bring too to the identification of therapies against these
      cellular target, fundamental for maintenance and progression of the lesion. Here,
      a literature review has been reported about the detection of supposed CSCs in
      head and neck cancer.

PMID- 17546611
TI  - Estimating inbreeding in large, semi-isolated populations: effects of varying
      generation lengths and of migration.
AB  - The purpose of the study reported here was to investigate two important
      assumptions used in a recently reported new method of estimating inbreeding in
      large, relatively isolated populations over historic times. The method, based on
      modeling the genealogical "paradox," produces values of Pearl's coefficients, Z,
      a measure of inbreeding or genealogical coalescence, as a function of time. In
      this study, the effects on inbreeding of two important assumptions made in
      earlier studies, namely those of using a constant generation length and of
      ignoring migration, have been investigated for the population of Britain. First,
      by relating the median age of women at childbirth to the development level of
      various societies, the variation of the generation lengths for different periods
      in historic Britain were estimated. Values of Z for two types of varying
      generation lengths were then calculated and compared with the case of constant
      generation length. Second, the population curve for Britain used in earlier
      studies was modified to obtain the subpopulation at any time during the past two
      millennia that was descended from the pre-Roman British Celts. Values of Z for
      the case with migration were then calculated and compared with the case for no
      migration. It is shown that these two assumptions may be taken into account if
      and when required. Both the effect of a varying generation length and the effect
      of migration on Z were found to be 20-40%, when no known value of inbreeding was
      used, and 2-5%, when a known value of inbreeding was used.

PMID- 17546612
TI  - Phenotypic plasticity and functional asymmetry in response to grip forces exerted
      by intercollegiate tennis players.
AB  - This study examined phenotypic and functional responses to extreme asymmetry in
      hand use, and recorded the grip forces that occur during the tennis serve to
      assess the forces that contribute to asymmetry. Compressive grip performance was
      measured for Division I collegiate tennis players (24 female, 24 male) and
      nonathlete college students (18 females, 17 males) during three experiments:
      single-repetition maximum voluntary contraction, 30 consecutive repetitions, and
      a 30-s static hold. Tennis players had significant asymmetry in both forearm
      circumference and grip strength. The dominant hand of female tennis players
      produced 25% more force than the opposite hand, while the difference between
      hands of male tennis players was 18%. However, endurance over 30-repetitions and
      during the 30-s hold did not significantly differ between the limbs of tennis
      players. No significant asymmetry in forearm measurements, grip strength, or
      endurance was detected between the limbs of nonathletes. Grip forces generated
      during the tennis serve were recorded for 4 male tennis players, using a racket
      with a dynamometer incorporated into the handle. Peak handgrip forces generated
      during the serve (150-250 N) averaged 31-44% of the maximum grip force of the
      participant. Tennis players have increased muscle mass and strength of the
      dominant limb. Moderate forces, occurring hundreds of times each match and
      practice, are likely the primary forces contributing to this morphological and
      functional asymmetry.

PMID- 17546613
TI  - Docosahexaenoic acid biosynthesis and dietary contingency: Encephalization
      without aquatic constraint.
AB  - Reconstructing evolutionary processes in the distant past is necessarily an
      inductive endeavor, typically appealing to numerous considerations thought to be
      relevant to the veracity of a particular conclusion. In this respect, it is
      essential that the considerations invoked to support hypotheses are in turn well
      established truths. It is with these concerns that we sought to examine the
      nutritional, physiological, and archeological premises underlying the perspective
      that access to an aquatic diet rich in docosahexaenoic acid (DHA, 22:6n-3) was
      critical to human brain evolution (Carlson and Kingston [2007]: Am J Hum Biol
      19:132-141). In our report investigating links between omega-3 (n-3) fatty acids
      and hominin encephalization, we concluded that the regular consumption of aquatic
      resources rich in preformed DHA may not have been essential given a varied diet
      of wild terrestrial foods (Carlson and Kingston [2007]). This assessment was
      based primarily on evidence of potential physiological adaptations in modern
      humans to ensure sufficient availability of DHA during critical periods of brain
      growth. While modern human physiology provides critical information regarding DHA
      as a constraint in evolving a large brain, it is also important to consistently
      contextualize interpretations within a framework of eclectic foraging diets
      rather than nutritionally limited modern agricultural populations or even modern
      foragers. We contend that current interpretations of Pleistocene hominin
      nutritional ecology do not uniquely support a shore-based foraging niche as
      claimed by Cunnane et al. ([2007]: Am J Hum Biol, 19:578-581). Specific issues
      raised in response to our article by Cunnane et al. and Joordens et al. ([2007]:
      Am J Hum Biol, 19:582-584) are addressed here.

PMID- 17546614
TI  - BMI, income, and social capital in a native Amazonian society: interaction
      between relative and community variables.
AB  - Researchers have shown interest in the relation between (a) social capital and
      individual income and (b) the individual health of people of industrial nations.
      The socioeconomic complexity of industrial nations makes it difficult to arrive
      at firm conclusions. We circumvent the obstacle by using data from a small-scale
      rural society of foragers-farmers in the Bolivian Amazon (Tsimane'). We examine
      the interactions between the outcome (BMI) and relative income, relative social
      capital, village income, and village social capital. We test three hypotheses:
      people in villages with more social capital should have higher BMI, the positive
      association between social capital and BMI will be more marked among the less
      well-off, and better-off people who display generosity will have higher BMI than
      better-off people who do not. On the methodological side we show the importance
      of: focusing on relative measures of income and social capital, estimating
      interaction between community and relative measures of income and social capital,
      and showing results through contour plots that summarize the relation between BMI
      and pairs of explanatory variables. On the substantive side we find evidence that
      village social capital and village income complement each other and are
      associated with higher BMI, the rich who are stingy have lower BMI than the rich
      who display generosity, and increase in village income might reduce individual
      incentives to invest in social capital. We explore interactions between
      explanatory variables and their influence on BMI, and end by recommending the use
      of an experimental research design to obtain unbiased estimates of causal
      effects.

PMID- 17546615
TI  - Comparison of methods to evaluate changes in relative body mass index in
      pediatric weight control.
AB  - Our objective was to compare three BMI-based adiposity measures to assess change
      in pediatric weight control: LMS z-BMI, BMI sympercent, and percent overBMI.
      Comparison 1 presents changes of +1.0, -1.0, and -2.0 BMI units for 36
      hypothetical children (7-, 11-, and 15-year-old children with BMI values from 19
      39 kg/m(2)). Comparison 2 presents effect sizes over 12 months and the
      relationship between baseline and change for 140 8-12-year-old children with BMI
      values ranging from 21 to 37 kg/m(2). Comparison 1 showed smaller changes in z
      BMI than BMI sympercent or percent overBMI for equal changes in BMI when initial
      BMI values are greater. Comparison 2 showed similar effect sizes for the three
      measures, since there is a reduction in both standard deviation and magnitude of
      LMS z-BMI values as the BMI values increase. The three measures perform
      differently when considering the relationship of initial value to change. Initial
      percent overBMI shows a negative relationship with change, as heavier children
      show larger changes, LMS z-BMI shows a positive relationship, as children with
      lower baseline values show larger changes, and BMI sympercent changes were
      inconsistently related to baseline BMI sympercent values. Although all three
      measures result in similar effect sizes when evaluating treatment over time, we
      conclude that LMS z-BMI is less appropriate for comparing individuals and percent
      overBMI is the only measure that shows heavier children have greater change.

PMID- 17546616
TI  - Advancing biocultural models by working with communities: a partnership approach.
AB  - Culture and human behavior are recognized today as major forces acting on human
      biological variation around the world. Studies of the relationships between
      biology and processes, such as modernization, urbanization, and social
      stratification, are prominent in our journals and meetings. An ongoing study of
      the interrelationships between toxicant exposure (organochlorines, lead, and
      mercury), health, and culture among youth of the Mohawk Nation at Akwesasne is
      located within this context and is used to analyze the strengths and challenges
      of a partnership approach to biocultural research. To assist in modeling the
      complex relationships between health, behavior, and culture, we have employed
      concepts from contemporary social theory, integrated qualitative and quantitative
      research, and implemented community-based research principles to develop a
      partnership approach to research in human biology. The community is directly
      involved in identifying research goals, developing research protocols appropriate
      for local cultural sensitivities and complexities, implementing the protocols in
      the field, and collaborating in the analysis and publication of results. We show
      the utility of this approach for understanding the relationships of toxicants to
      behavior and biological outcomes (adolescent growth, sexual maturation, and
      endocrine system alteration); as well as how it facilitates the agency of
      participants and communities involved in research, and brings greater social
      engagement to the development of the new human biology.

PMID- 17546617
TI  - Do children take the same number of steps every day?
AB  - The purpose of this study was to examine the day-to-day variability in pedometer
      assessed physical activity (steps/day). A total of 1,443 children aged 6-12 years
      from the United States (195 boys, 254 girls), Sweden (257 boys, 252 girls), and
      Australia (229 boys, 256 girls) wore a pedometer for 4 consecutive weekdays.
      Repeated measures analysis of variance was used to examine daily differences in
      steps/day and the coefficient of variation (CV) was calculated for each
      individual to describe the day-to-day variability. Overall, mean steps/day were
      higher among boys (14,698 +/- 3,373 steps/day) than girls (12,086 +/- 2,929
      steps/day). Significant differences were found between the 4 monitoring days for
      the entire sample; however, the absolute mean differences were small (55-958
      steps) with an overall effect size of 0.01. This trend was apparent regardless of
      age, gender, and country. Individual CVs ranged from approximately 2 to 88% and
      the overall mean CV approximated 22%. An age-related increase in the mean CV was
      observed between 6- and 12-year-old children. The age x gender x country
      interaction was not significant (P > 0.05). These findings have implications
      toward the proper design, analysis, and interpretation of studies regarding
      physical activity among children. Beyond this aspect, our results lend insight
      into potential age-related biological mechanisms that may also influence daily
      levels and patterns of physical activity.

PMID- 17546618
TI  - Sex differences in young adulthood metabolic syndrome and physical activity: the
      Fels longitudinal study.
AB  - OBJECTIVE: To evaluate the effects of habitual physical activity (PA) on the
      metabolic syndrome (MS) in young adult men and women. RESEARCH METHODS AND
      PROCEDURES: Cross-sectional PA data were utilized from 249 women and 237 men,
      aged 18-40 years in the Fels Longitudinal Study. MS components--abdominal
      circumference (AC), triglycerides (TG), HDL, blood pressure (BP), and fasting
      glucose (FG)--were dichotomized according to the National Cholesterol Education
      Program's Adult Treatment Panel III revised criteria. Leisure, sport, work, and
      total PA scores were calculated using the Baecke Questionnaire of Habitual
      Physical Activity. Multiple logistic regression modeling assessed the effects of
      PA, age, smoking, and BMI on MS status. RESULTS: 26.9% of men and 19.3% of women
      had MS. For men, MS risk was reduced with increases in both total PA [OR = 0.65
      (95% CI: 0.47, 0.90)] and sport PA [OR = 0.40 (95% CI: 0.23, 0.70)]. AC, TG, and
      HDL values also improved with total and sport PA. Among women, the risk for MS
      was marginally reduced by total PA [OR = 0.72 (95% CI: 0.50, 1.02)] and HDL
      levels were increased by both total PA [OR = 0.79 (95% CI: 0.63, 0.98)] and sport
      PA [OR = 0.54 (95% CI: 0.35, 0.84)]. DISCUSSION: Increased total and sport PA
      reduces risk for the MS in young men, though not as clearly in young women.

PMID- 17546619
TI  - Variations in RANK gene are associated with adult height in Caucasians.
AB  - Height is a complex trait significantly influenced by genetic factors, with
      heritability ranging from 48% to 98%. Previous studies have yielded a number of
      important genomic regions that may account for the variation of height in human
      populations. However, more 'height' genes still wait for identification. Recent
      studies have revealed that tumor necrosis factor receptor superfamily member 11a
      (RANK) is a vital factor for chondroclastic/osteoclastic differentiation and
      activity that influence the morphology of growth plates and linear bone growth.
      Despite its importance, little effort has been made to find out whether the RANK
      polymorphisms are associated with adult height variation in normal populations.
      Herein, we performed a family based association test (FBAT) in 1873 white
      subjects from 405 nuclear families. Among eighteen single nucleotide
      polymorphisms (SNPs) and seven blocks, SNP rs6567274 was detected to be
      significant even after multiple-testing correction. In corroboration with single
      locus analysis, a major haplotype in block 5 bearing the variant "T" of rs6567274
      was significantly associated with higher stature. Our findings firstly suggested
      the RANK polymorphisms might contribute to adult height variation. Further
      researches need to be launched to replicate the present results and further
      unravel the molecular mechanism underlying the significant associations
      discovered.

PMID- 17546620
TI  - Docosahexaenoic acid and shore-based diets in hominin encephalization: a
      rebuttal.
AB  - Carlson and Kingston ([2007]: Am J Hum Biol 19:132-141) propose that preformed
      dietary docosahexaenoic acid (an omega-3 fatty acid in fish) did not have a
      significant role in hominin encephalization. Their position hinges on claiming
      that humans are able to make sufficient docosahexaenoic acid from the plant-based
      "parent" omega-3 fatty acid-alpha-linolenic acid. They also suggest that hominin
      fish consumption occurred too late to have materially influenced encephalization.
      The authors quantify here a summary of the published data showing that humans
      cannot make sufficient docosahexaenoic acid to maintain normal infant brain
      development. The authors also provide evidence that the fossil record shows that
      some of the earliest hominins were regularly consuming fish. Hence, we reject
      Carlson and Kingston's position and reiterate support for the concept that access
      to shore-based diets containing docosahexaenoic acid was necessary for hominin
      encephalization beyond the level seen in the great apes.

PMID- 17546621
TI  - Preformed dietary DHA: The answer to a scientific question may in practice become
      translated to its opposite.
AB  - In a previous issue of AJHB, Carlson and Kingston ([2007]: Am J Hum Biol 19:132
      141) raised the question whether modern humans need preformed docosahexaenoic
      acid (DHA) from the aquatic food chain in their diet. The authors concluded that
      at the moment, there is not sufficient hard evidence to answer this scientific
      question in a positive way. In our comment on their review, we argue that because
      results from various studies and trials strongly indicate a positive correlation
      between preformed dietary DHA and human health and development, it may be a risky
      strategy to await the ultimate evidence before recommending the inclusion of
      sufficient seafood or fish oil supplements in the modern human diet.

PMID- 17546622
TI  - Multiple mortality optima due to heterogeneity in the birth cohort: a continuous
      model of birth weight by gestational age-specific infant mortality.
AB  - Birth weight and gestational age are both important predictors of infant
      survival. Covariate Density Defined mixture of logistic regressions (CDDmlr), a
      method that accounts for unobserved heterogeneity, has been applied to birth
      outcomes using birth weight alone. This paper investigates a CDDmlr model of
      birth outcomes that includes birth weight and gestational age. Applications to
      four birth cohorts, composed of all non-Hispanic singleton African/European
      American female/male live births in New York State from 1985-1988, are presented.
      Multiple birth weight by gestational age optimal (minimal) mortalities are
      observed in the birth weight by gestational age-specific mortality surface.
      Multiple optima have not been mentioned in the published literature, but they do
      appear in some published plots of birth weight by gestational age mortality. It
      is possible that misreporting of gestational age contributes to this phenomenon,
      but it cannot completely explain the locations of the local optima. The global
      optimum is associated with a "normal" fetal development subpopulation, while the
      local optima are due to a subpopulation that accounts for most low birth weight,
      intrauterine growth retarded, pre-term, post-term, and small for gestational age
      births, as well as, births with misestimated gestational ages. These two
      subpopulations have significantly different birth weight by gestational age
      specific mortality surfaces. Consequently, the presence of multiple optima can be
      attributed to heterogeneity in the birth cohort. Comparisons of CDDmlr based on
      birth weight by gestational age and birth weight alone might statistically
      identify births with "erroneous" gestational age.

PMID- 17546623
TI  - MGEA5-14 polymorphism and type 2 diabetes in Mexico City.
AB  - A family-based study has recently reported that a variant located in intron 10 of
      the gene MGEA5 increases susceptibility to Type 2 Diabetes (T2D). We evaluated
      the distribution of this SNP in a sample of T2D patients (N = 271) and controls
      (N = 244) from Mexico City. The frequency of the T allele was higher in the cases
      (2.6%) than in the controls (1.8%). After adjusting for age, sex, BMI, education,
      and individual ancestry the odds ratio was 1.60 but the 95% confidence interval
      was wide and overlapped 1 (0.52-4.86, P-value : 0.404). In order to characterize
      the distribution of the MGEA5-14 polymorphism in the relevant parental
      populations, we genotyped this variant in European (and European Americans), West
      African, and Native American samples. The T-allele was present at a frequency of
      2.3% in Spain, 4.2% in European Americans, and 13% in Western Africans, but was
      absent in two Native American samples from Mexico and Peru. Given the low
      frequency of the T-allele, further studies using large sample sizes will be
      required to confirm the role of this variant in T2D.

PMID- 17546624
TI  - Interleukin-4 antagonizes oncostatin M and transforming growth factor beta
      induced responses in articular chondrocytes.
AB  - Oncostatin M (OSM) stimulates cartilage degradation in rheumatoid arthritis (RA)
      by inducing matrix metalloproteinases (MMPs) and aggrecanases (ADAMTS; a
      disintegrin and metalloproteinase with thrombospondin motif). Transforming growth
      factor beta (TGF-beta1) induces cartilage repair in joints but in excessive
      amounts, promotes inflammation. OSM and TGF-beta1 also induce tissue inhibitor of
      metalloproteinase-3 (TIMP-3), an important natural inhibitor of MMPs,
      aggrecanases, and tumor necrosis factor alpha converting enzyme (TACE), the
      principal proteases involved in arthritic inflammation and cartilage degradation.
      We studied cartilage protective mechanisms of the antiinflammatory cytokine,
      interleukin-4 (IL-4). IL-4 strongly (MMP-13 and TIMP-3) or minimally (ADAMTS-4)
      suppressed OSM-induced gene expression in chondrocytes. IL-4 did not affect OSM
      stimulated phosphorylation of extracellular signal-regulated kinases (ERKs),
      protein 38 (p38), c-Jun N-terminal kinase (JNK) and Stat1. Lack of additional
      suppression with their inhibitors suggested that MMP-13, ADAMTS-4, and TIMP-3
      inhibition was independent of these mediators. IL-4 also downregulated TGF-beta1
      induced TIMP-3 gene expression, Smad2, and JNK phosphorylation. Additional
      suppression of TIMP-3 RNA by JNK inhibitor suggests JNK implication. The
      cartilage protective effects of IL-4 in animal models of arthritis may be due to
      its inhibition of MMPs and ADAMTS-4 expression. However, suppression of TIMP-3
      suggests caution for using IL-4 as a cartilage protective therapy.

PMID- 17546625
TI  - Synergistic induction of osteopontin by aldosterone and inflammatory cytokines in
      mesangial cells.
AB  - Hypertensive nephrosclerosis is characterized by activation of the renin
      angiotensin-aldosterone system in combination with an inflammatory response
      characterized by an infiltration of T-cells and mononuclear cells, which release
      proinflammatory cytokines like IL-1beta/TNFalpha. In various models of
      experimental hypertensive disease the chemokine osteopontin (OPN) enhances
      further leukocyte infiltration. Therefore, we investigated the induction of OPN
      expression in renal mesangial cells (MCs) by aldosterone and the inflammatory
      cytokines IL-1beta/TNFalpha. Incubation with aldosterone resulted in a time- and
      concentration-dependent increase in OPN mRNA and protein. OPN mRNA expression
      followed a biphasic time course with an early increase between 4 and 8 h and the
      second phase starting at 14 h. The early phase was independent of protein
      synthesis, indicating a direct effect of aldosterone. Aldosterone-mediated
      induction of OPN was prevented by spironolactone, indicative of a receptor
      mediated aldosterone effect. The mineralocorticoid receptor (MR) was identified
      in MCs by RT-PCR and immunoprecipitation, and shown to interact with a putative
      aldosterone-response element of the OPN promoter. The proinflammatory cytokines
      IL-1beta and TNFalpha only marginally affected OPN expression in MCs. However,
      coincubation of aldosterone and the cytokines synergistically increased OPN mRNA
      and protein levels. Since the synergistic effect on OPN mRNA was inhibited by
      diphenyleneiodonium, we assume an involvement of reactive oxygen species (ROS).
      We conclude that the chemokine OPN is a target gene of aldosterone in renal MCs,
      which is activated via the MR, and that proinflammatory cytokines enhance
      aldosterone-dependent OPN expression. In vivo, this may result in further
      leukocyte infiltration aggravating hypertensive nephrosclerosis.

PMID- 17546626
TI  - The cyclooxygenase-2-mediated prostaglandin signaling is causally related to
      epithelial carcinogenesis.
AB  - Epidemiologic, pharmacologic, clinical, and experimental studies document the
      importance of prostaglandin (PG) signaling in cancer development, including non
      melanoma skin cancer lesions in humans and mice. First of all, enzymes involved
      in PG biosynthesis, such as cyclooxygenase (COX)-2 and/or membrane prostaglandin
      E synthase (mPGES)-1, were found to be overexpressed in a wide range of
      premalignant and malignant epithelial tumors, including those of the skin,
      breast, esophagus, stomach, colorectum, pancreas, and bladder. On the other hand,
      15-hydroxy-prostaglandin dehydrogenase (15-PGDH), which is involved in the
      degradation pathway of PG including PGE(2,) thus counteracting the activities of
      COX-2 and PGES, was found to be downregulated in human epithelial tumors,
      indicating a tumor suppressor activity of this enzyme. Most remarkably, genetic
      studies showed that mice, which are deficient in COX-2 and/or PGES are resistant
      to the development of cancer of skin, colon, and stomach. In contrast, the forced
      overexpression of COX-2 in proliferative compartments of simple or stratified
      epithelia such as skin epidermis, urinary bladder, mammary gland, and pancreas
      results in spontaneous hyperplasia and dysplasia in transgenic mice. In skin, the
      pathological changes are found to be due to an abnormal process of terminal
      differentiation, while in other tissues, hyperproliferation seems to be the main
      contributor to the pre-invasive neoplasms. Moreover, the COX-2 transgenic mouse
      lines are sensitized for cancer development.

PMID- 17546627
TI  - Low p38 MAPK and JNK activation in cultured hepatocytes of DRH rats; a strain
      highly resistant to hepatocarcinogenesis.
AB  - DRH rats are a hepatocarcinogenesis-resistant strain isolated from
      hepatocarcinogenesis-sensitive Donryu rats, and the liver of DRH shows less
      histological damage and fewer/smaller neoplastic hepatic lesions by the treatment
      with hepatocarcinogens. To investigate the mechanism of the resistance, the
      properties of hepatocytes of DRH and Donryu were compared. In primary culture,
      DRH hepatocytes exhibited higher proliferation and less apoptosis than Donryu
      hepatocytes in the presence of EGF and insulin. However, such difference was not
      correlated to the degree of DNA damage associated with cell culture or cell cycle
      checkpoint function. Although the mitogen-activated protein kinases [EGF receptor
      (EGFR) and extracellular signal regulating kinases (ERK1/2)] were activated to
      the same degree, the stress-activated protein kinases [p38 mitogen-activated
      protein kinase (p38) and c-jun N-terminal kinase (JNK)] were activated to a
      lesser degree in the DRH hepatocytes. Treatment with 2-acetylaminofluorene (2
      AAF) in vivo also resulted in less JNK and p38 activation in the DRH livers.
      Furthermore, apoptosis signal-regulating kinase 1 (ASK1) was inhibited by the
      lysate from the DRH but not by the Donryu hepatocytes. The low activation of the
      stress-activated protein kinases may be linked to the resistance to cellular
      stress, which may underlie the hepatocarcinogenesis-resistance in DRH rats.

PMID- 17546628
TI  - Association of matrix metalloproteinase-2 and -9 promoter polymorphisms with
      colorectal cancer in Chinese.
AB  - Matrix metalloproteinase-2 (MMP-2) and -9 (MMP-9) play an important role in
      cancer initiation, invasion, and metastasis. The aim of this study was to
      investigate whether common genetic variants in these two key MMPs are associated
      with the development and progression of colorectal cancer in a Chinese
      population. We detected the MMP-2-790T/G, -955A/C, -1575G/A, and MMP-9-1562 C/T
      polymorphisms in 126 colorectal cancer patients and matched normal controls by
      PCR-denaturing high-performance liquid chromatography (DHPLC) or PCR-restriction
      fragment length polymorphism (RFLP), respectively. We found that the G/G genotype
      in the MMP-2-1575G/A polymorphism was significantly increased in colorectal
      cancer patients than in the controls (odds ratio (OR), 1.96; 95% CI, 1.06-3.64).
      Colorectal cancers with G/G genotype were more common with serosa/adventitia
      layer involvement than those with G/A+A/A genotypes (P<0.05). However, no
      significant differences were observed in distribution of the MMP-2-790T/G, 
      955A/C, and MMP-9-1562 C/T polymorphisms or haplotype of MMP-2 SNPs between
      patients and controls. Our results suggest that the presence of -1575G allele in
      the MMP-2 promoter region may be of significance in the assessment of colorectal
      cancer risk and invasive potential.

PMID- 17546629
TI  - Public safety aspects of pyrethroid insecticides used in West Nile virus-carrying
      mosquito control.
AB  - West Nile virus is becoming increasingly prevalent in the USA, causing fever,
      encephalitis, meningitis and many fatalities. Spread of the disease is reduced by
      controlling the mosquito vectors by a variety of means, including the use of
      pyrethroid insecticides, which are currently under scrutiny for potential
      carcinogenic effects in humans. Pyrethrins and resmethrin, a pyrethroid, have
      been shown to cause tumours in rat and mouse models respectively. However, the
      tumours appear to be caused by liver enzyme induction and hypertrophy rather than
      genotoxicity, and the results are therefore unlikely to be applicable to humans.
      Nonetheless, for resmethrin, the US Environmental Protection Agency (EPA) has
      concluded that there is a likely risk of carcinogenicity in humans, requiring the
      manufacturers to provide more detailed data to prove that it can be used safely
      in vector control. Reproductive toxicity of resmethrin in the rat is also
      discussed.

PMID- 17546630
TI  - Dynamic changes in the localization of five members of the methyl binding domain
      (MBD) gene family during murine and bovine preimplantation embryo development.
AB  - There are five methyl binding domain (MBD) proteins characterized by a methyl CpG
      binding domain. Four MBD proteins (MeCP2 and MBDs 1-3) are linked to
      transcriptional repression and one (MBD4), to DNA repair. During preimplantation
      development, the embryo undergoes global demethylation following fertilization
      and selective remethylation following the maternal to zygotic transition (MZT).
      This study characterized changes in MBD mRNA expression and protein localization
      during both murine and bovine preimplantation development. These species were
      selected because they undergo MZT at different developmental stages. Gene
      expression profiling during preimplantation development detected the presence of
      all MBDs examined, although stage and species-specific differences were observed.
      MBD2 was not expressed in murine or bovine oocytes and MeCP2 was not detected in
      murine blastocysts, subcellular protein localization was found to vary at time
      points critical in development. Most MBDs showed species-specificity in
      localization patterns and differences were found between individual MBDs. MBD1
      localization is consistent with a novel role during MZT for both species. MBD3,
      known to play a crucial role in murine embryogenesis, was highly localized to the
      nucleus before and after, but not during the MZT in the bovine. MBD2, MBD4, and
      MeCP2 show varying patterns of localization which indicate possible roles in the
      early cleavage stages and in inner cell mass differentiation. Further experiments
      are currently underway to define discreet functional roles for specific MBDs
      during bovine preimplantation embryogenesis.

PMID- 17546631
TI  - Multiple myeloma: a prototypic disease model for the characterization and
      therapeutic targeting of interactions between tumor cells and their local
      microenvironment.
AB  - The interaction between tumor cells and the local milieu where are homing has
      recently become the focus of extensive research in a broad range of malignancies.
      Among them, multiple myeloma (MM) is now recognized as a prototypical tumor model
      for the characterization of these interactions. This is due not only to the
      propensity of MM cells to target the skeleton and form lytic bone lesions, but
      because interactions of MM cells with normal cells of the bone milieu can
      attenuate the anti-tumor activity of conventional therapies, such as
      glucocorticoids and standard cytotoxic agents, including alkylators. Herein, we
      highlight the recent advances in our understanding of cellular and molecular
      mechanisms of interactions between MM cells and their milieu. Particular emphasis
      is placed on the interface between MM cells and normal cell compartments of the
      BM, especially bone marrow stromal cells (BMSCs), and on the development of a
      series of new classes of therapeutic agents, including the proteasome inhibitor
      bortezomib, thalidomide and lenalidomide, which counteract specific aspects of
      those MM-BM interactions. The significant clinical activity of these novel
      therapies has not only led to a new era in the therapeutic management of this
      disease, but also underscored the importance of comprehensively characterizing
      the role of the local microenvironment in the pathophysiology of human
      neoplasias.

PMID- 17546632
TI  - Impaired cytotrophoblast cell-cell fusion is associated with reduced Syncytin and
      increased apoptosis in patients with placental dysfunction.
AB  - Preeclampsia (PE), Hemolysis Elevated Liver Enzymes and Low Platelets (HELLP)
      syndrome, and intrauterine growth restriction (IUGR) are associated with abnormal
      placentation. In early pregnancy, placental cytotrophoblasts fuse and form
      multinuclear syncytiotrophoblasts. The envelope gene of the human endogenous
      retrovirus-W, Syncytin, is a key factor for mediating cell-cell fusion of
      cytotrophoblasts. This study investigated clinical parameters of PE and HELLP
      associated IUGR and analyzed the cell-cell fusion index and beta-human chorionic
      gonadotropin (beta-hCG) secretion of cytotrophoblasts isolated and cultured from
      placentas of these patients. In addition, we performed absolute quantitation of
      Syncytin and determined the apoptosis rate in both cultured cytotrophoblasts and
      placental tissues. Cultured cytotrophoblasts from PE and HELLP-associated IUGR
      correlated with a pronounced lower cell-cell fusion index, 1.8- and 3.6-fold;
      less nuclei per syncytiotrophoblast, 1.4- and 2.0-fold; a significantly decreased
      beta-hCG secretion, 4.3- and 17.2-fold and a reduction of Syncytin gene
      expression, 8.1 (P = 0.019) and 222.7-fold (P = 0.011) compared with controls,
      respectively. In contrast, a significantly 2.3-fold higher apoptosis rate was
      observed in cultured PE/IUGR cytotrophoblasts (P = 0.043). Importantly, Syncytin
      gene expression in primary placental tissues of PE/IUGR was 5.4-fold lower (P =
      0.047) and in HELLP/IUGR 10.6-fold lower (P = 0.019) along with a 1.8- and 1.9
      fold significant increase in the apoptosis rate compared with controls,
      respectively. Low Syncytin expression in both cultured cytotrophoblasts and
      primary tissues from pathological placentas supports an intrinsic placenta
      specific deregulation of cell-cell fusion in the formation of
      syncytiotrophoblasts leading to increased apoptosis. These processes could
      contribute to the development and severity of PE and HELLP-associated IUGR.

PMID- 17546633
TI  - Transient transgene transmission to piglets by intrauterine insemination of
      spermatozoa incubated with DNA fragments.
AB  - An efficient and low-cost production of transgenic pigs has significant
      applications to the pig industry and biomedical science. Generation of transgenic
      pig by sperm-mediated gene transfer (SMGT) was inexpensive and convenient, and
      reported with high efficiency. To test the method of SMGT in pigs, we employed
      deep post-cervical intrauterine insemination of incubated spermatozoa in this
      study. A test of sperm motility of semen from nine Landrace boars after
      incubation with radioactively labeled DNA construct indicated that DNA uptake of
      the sperm was highly correlated with sperm motility at the time of collection.
      DNA concentration of 50 and 300 microg per one billion sperm was incubated with
      washed high-motility sperm at 17 degrees C for 2 hr. Twenty one hybrid gilts and
      sows of Meishan crossed with Large White were inseminated with transgene
      incubated sperm and produced 156 piglets. Transgene DNA sequences were identified
      in 31 piglets by PCR amplification of genomic DNA isolated from piglet ears at
      the age of 3 days. The deep intrauterine insemination had a higher rate of
      positive transgenic piglets than regular insemination (29.6% of 98 piglets vs.
      3.4% of 58 piglets). However, the exogenous transgene DNA was not detected in any
      piglets at the age of 70-100 days. Therefore, the results further demonstrated
      that transgene through incubation with spermatozoa was mostly transiently
      transmitted to the offspring at early growing stage and lost in adulthood, which
      may result from episomal DNA replications during cell divisions only at the early
      stage of development.

PMID- 17546634
TI  - Chronic thrombopoietin overexpression induces mesangioproliferative
      glomerulopathy in mice.
AB  - We previously reported that mice transgenic (Tg) for thrombopoietin (TPO)
      developed progressive fibrosis and osteosclerosis of the bone marrow. Here, we
      show that TPO-overexpressing mice also exhibited notable histological changes in
      the kidneys, including an increased number of mesangial cells, expansion of the
      mesangial matrix in the glomerulus, and atrophy of the renal tubuli. Plasma
      transforming growth factor (TGF)-beta1 and platelet-derived growth factor (PDGF)
      BB, which could induce mesangioproliferative responses in glomeruli, were both
      elevated in TPO Tg mice, even though TPO itself has no effect on mesangial cells
      due to their lack of c-Mpl. The mesangial proliferative change in TPO Tg mice was
      thought to be induced by the elevation of these cytokines. In conclusion, our
      finding that TPO-overexpressing mice developed mesangioproliferative
      glomerulopathy might represent an undesirable effect of chronically elevated TPO
      in vivo, which should be taken into consideration before new TPO-like growth
      factors become available in clinical practice.

PMID- 17546635
TI  - Successful treatment of pure red cell aplasia with autologous stem cell
      transplantation.
AB  - We report a case of 64-year-old patient with pure red cell aplasia (PRCA) who was
      intolerant of conventional immunosuppressive therapies but achieved a complete
      long-term remission following autologous hematologic stem cell transplant (HSCT).
      The patient was initially treated with high-dose prednisone, cyclophosphamide,
      cyclosporine, antithymocyte globulin, and then rituximab. With the exception of
      rituximab, all of the above regimens achieved a transient response. However,
      because of the persistent requirement for red blood cell transfusions and
      intolerance to the multiple immunosuppressive therapies, autologous HSCT was
      eventually performed. The patient remains in complete remission and on no other
      therapy for 36 months following the autologous HSCT.

PMID- 17546636
TI  - Bexarotene blunts malignant T-cell chemotaxis in Sezary syndrome: reduction of
      chemokine receptor 4-positive lymphocytes and decreased chemotaxis to thymus and
      activation-regulated chemokine.
AB  - The malignant cells in Sezary syndrome express the skin trafficking molecules'
      cutaneous lymphocyte associated antigen (CLA) and chemokine receptor 4 (CCR4).
      High levels of the CCR4 ligand, thymus, and activation-regulated chemokine
      (TARC), have been reported in the blood and skin of patients. The rexinoid X
      receptor specific retinoid, bexarotene, has contributed to the resolution of
      cutaneous disease among patients. To evaluate the effects of bexarotene on skin
      trafficking molecule expression and chemotaxis, peripheral blood mononuclear
      cells from Sezary syndrome patients and healthy controls were treated with
      bexarotene in vitro. CCR4 and CLA expression levels and chemotaxis in response to
      TARC (6.25 ng/ml) were evaluated among lymphocytes before and after treatment
      with bexarotene (10 microM). Flow cytometric analysis was performed to evaluate
      CD4, CD26, CLA, and CCR4 cell surface expression. Transwell migration assays were
      performed to evaluate chemotaxis to TARC. Prior to treatment, malignant cells
      exhibited higher CCR4 expression (45-90%) and greater than four times more
      chemotaxis to TARC compared with healthy controls. After treatment with
      bexarotene for 36-96 hr, a 28% reduction in CCR4 expression was noted (P < 0.05)
      among the malignant population with an associated 9% decrease in chemotaxis to
      TARC (P < 0.05). Our results show that bexarotene may inhibit malignant cell
      trafficking to the skin through an ability to suppress CCR4 expression among
      Sezary syndrome lymphocytes.

PMID- 17546637
TI  - Polymorphisms involved in the folate metabolizing pathway and risk of multiple
      myeloma.
AB  - Folate and methionine metabolism plays an essential role in both DNA synthesis
      and methylation. Polymorphisms in the genes of the folate-dependent enzymes have
      been shown to affect disease susceptibility. We conducted a Korean population
      based case-control study to evaluate whether genetic variation in folate
      metabolism may have a role in the risk of multiple myeloma (MM). The study
      subjects were 173 patients with MM and 1,700 population-based controls. The
      polymorphisms studied include methylenetetrahydrofolate reductase (MTHFR) 677 C >
      T and 1298 A > C, methionine synthase (MS) 2756 A > G, methionine synthase
      reductase (MTRR) 66A > G, thymidylate synthase (TS) 28-bp repeat (2R-->3R) and 6
      bp deletion/insertion. MS 2756 AG genotypes were associated with a 1.5-fold lower
      risk of MM (OR = 0.66, 95%CI; 0.43-0.99, P = 0.047). There was no association
      between MTHFR C677T, A1298C, MTRR A66G, TS 2R-->3R and 6-bp deletion/insertion
      polymorphisms and MM. These results suggest that MTHFR C677T, A1298C, MTRR A66G,
      TS 2R-->3R, and 6-bp deletion/insertion do not significantly factor into the
      pathogenesis of MM in the Korean population, but that MS A2756G polymorphism may
      play an important role.

PMID- 17546638
TI  - Hypermethylation of the p15INK4B gene promoter in B-chronic lymphocytic leukemia.
AB  - The p15 gene is a putative tumor suppressor gene that encodes a member of the
      cyclin dependent kinase inhibitors. Inactivation of p15 by promoter
      hypermethylation has been postulated as a possible way by which tumor suppressor
      genes are inactivated in cancer. In this study, we examined the methylation
      status of the p15 gene promoter in 34 patients with B-Chronic Lymphocytic
      Leukemia (B-CLL), by the Methylation-Specific Polymerase Chain Reaction.
      Selective methylation of the p15 gene promoter was found in 4/34 cases (11.8%).
      According to Rai staging, the four patients with methylated p15 were staged on
      diagnosis as: 1 on Stage 0, 1 in Stage I, 1 in Stage III, and 1 in Stage IV. Our
      results suggest that methylation of the p15 gene promoter can be detected in a
      small subset of B-CLL patients, at all stages of the disease.

PMID- 17546639
TI  - Predictive value of alkaline phosphatase for response and time to progression in
      bortezomib-treated multiple myeloma patients.
AB  - Myeloma bone disease is characterized by osteolytic destruction associated with
      suppressed osteoblastic activity. Using data from the APEX (Richardson et al., N
      Engl J Med 2005;352:2487-2498) study, we have assessed the relationship of
      changes in alkaline phosphatase (ALP) levels during bortezomib therapy with
      response and time to progression on this therapy. The percentage of ALP
      increments in responders (complete and partial response) and nonresponders was
      analyzed at different thresholds and time points. For all bortezomib-treated
      patients enrolled in the trial (N = 333), at least a 25% increase in ALP from the
      baseline at 6 week was the most powerful predictor of treatment response (P <
      0.0001) and time to progression (206 vs. 169 days) relative to patients with less
      than a 25% increase in ALP (P = 0.01). Markers of osteoblastic activation may
      predict quality and duration of response in multiple myeloma. In addition, our
      data suggest that bone anabolism could inhibit myeloma growth.

PMID- 17546640
TI  - Detection of genomic copy number changes in patients with idiopathic mental
      retardation by high-resolution X-array-CGH: important role for increased gene
      dosage of XLMR genes.
AB  - A tiling X-chromosome-specific genomic array with a theoretical resolution of 80
      kb was developed to screen patients with idiopathic mental retardation (MR) for
      submicroscopic copy number differences. Four patients with aberrations previously
      detected at lower resolution were first analyzed. This facilitated delineation of
      the location and extent of the aberration at high resolution and subsequently,
      more precise genotype-phenotype analyses. A cohort of 108 patients was screened,
      57 of which were suspected of X-linked mental retardation (XLMR), 26 were
      probands of brother pairs, and 25 were sporadic cases. A total of 15 copy number
      changes in 14 patients (13%) were detected, which included two deletions and 13
      duplications ranging from 0.1 to 2.7 Mb. The aberrations are associated with the
      phenotype in five patients (4.6%), based on the following criteria: de novo
      aberration; involvement of a known or candidate X-linked nonsyndromic(syndromic)
      MR (MRX(S)) gene; segregation with the disease in the family; absence in control
      individuals; and skewed X-inactivation in carrier females. These include
      deletions that contain the MRX(S) genes CDKL5, OPHN1, and CASK, and duplications
      harboring CDKL5, NXF5, MECP2, and GDI1. In addition, seven imbalances were
      apparent novel polymorphic regions because they do not fulfill the proposed
      criteria. Taken together, our data strongly suggest that not only deletions but
      also duplications on the X chromosome contribute to the phenotype more often than
      expected, supporting the increased gene dosage mechanism for deregulation of
      normal cognitive development.

PMID- 17546641
TI  - Granular acute lymphoblastic leukemia: a case report and literature review.
AB  - Authors report a rare case of granular acute lymphoblastic leukemia (ALL) in a 45
      year-old woman with a history of multiple myeloma. The patient's lymphoblasts
      contained large numbers of distinctive cytoplasmic granules closely mimicking
      heavily granulated myeloblasts in acute myeloid leukemia. These blasts were
      completely negative for myeloperoxidase but positive for acid phosphatase and
      Periodic Acid-Schiff reaction by cytochemical staining. Immunophenotype analysis
      by immunohistochemistry clearly demonstrated precursor B-cell phenotype. Granular
      ALL occurs approximately 2 to 7% in childhood populations but is extremely rare
      in adults. Such cases may cause problematic distinction from myeloid
      differentiation and lead to misdiagnosis of acute myeloid leukemia. Ten cases of
      adult granular acute lymphoblastic leukemia described to date in the literature
      were also reviewed.

PMID- 17546644
TI  - Fragmentation study on the phenolic alkaloid neferine and its analogues with anti
      HIV activities by electrospray ionization tandem mass spectrometry with
      hydrogen/deuterium exchange and its application for rapid identification of in
      vitro microsomal metabolites of neferine.
AB  - The application of mass spectrometry in drug discovery, especially in drug
      metabolites, is very important. This present paper is at first focused on the
      elucidation of fragmentation patterns of the phenolic
      bisbenzyltetrahydroisoquinoline alkaloid, neferine, together with its analogues
      isoliensinine and liensinine with anti-HIV activities using electrospray
      ionization tandem mass spectrometry (ESI-MS/MS) and hydrogen/deuterium (H/D)
      exchange. All title compounds displayed major diagnostic fragments that formed by
      the cleavage of the C1'--C9' bond resulting in positive group CD, and the loss of
      4-ethyl-1-phenol or 4-ethyl-1-methoxybenzene following rearrangements. Their ESI
      MS/MS spectra also showed the relatively stable fragment ions formed by the
      elimination of H2O, CH3NH2, CH3OH, and CH3-N==CH2. Secondly, the metabolites of
      neferine from dog hepatic microsomal incubations were analyzed and characterized
      by high-performance liquid chromatography (HPLC) and data-dependent ESI-MS/MS.
      Based on fragmentation patterns and compared with their retention times in LC,
      molecular weights and ultraviolet (UV) absorbances with standard compounds, six
      metabolites were identified as isoliensinine, liensinine and four novel
      bisbenzyltetrahydroisoquinoline alkaloids named as 6-O-desmethylneferine, 2'-N
      desmethylneferine, 2'-N-6-O-didesmethylneferine, and 6,13-O-didesmethylneferine.
      All metabolites were desmethyl or didesmethyl products of neferine. The possible
      metabolic pathways for neferine have been proposed. The results suggest that N
      demethylation and O-demethylation are two important metabolic pathways of
      neferine in dog hepatic microsomal incubations. This is critical for screening
      and development of phenolic bisbenzyltetrahydroisoquinoline alkaloids with anti
      HIV activities such as neferine and its analogues isoliensinine and liensinine.

PMID- 17546645
TI  - Mutational spectrum of MYO15A: the large N-terminal extension of myosin XVA is
      required for hearing.
AB  - Human MYO15A is located on chromosome 17p11.2, has 66 exons and encodes
      unconventional myosin XVA. Recessive mutations of MYO15A are associated with
      profound, nonsyndromic hearing loss DFNB3 in humans, and deafness and circling
      behavior in shaker 2 mice. In the inner ear, this motor protein is necessary for
      the development of hair cell stereocilia, which are actin-filled projections on
      the apical surface and the site of mechanotransduction of sound. The longest
      isoform of myosin XVA has 3,530 amino acid residues. Two isoform classes of
      MYO15A are distinguished by the presence or absence of 1,203 residues preceding
      the motor domain encoded by alternatively-spliced exon 2. It is not known whether
      this large N-terminal extension of myosin XVA is functionally necessary for
      hearing. We ascertained approximately 600 consanguineous families segregating
      hereditary hearing loss as a recessive trait and found evidence of linkage of
      markers at the DFNB3 locus to hearing loss in 38 of these families ascertained in
      Pakistan (n=30), India (n=6), and Turkey (n=2). In this study, we describe 16
      novel recessive mutations of MYO15A associated with severe to profound hearing
      loss segregating in 20 of these DFNB3-linked families. Importantly, two
      homozygous mutant alleles-c.3313G>T (p.E1105X) and c.3334delG (p.G1112fsX1124) of
      MYO15A-located in exon 2 are associated with severe to profound hearing loss
      segregating in two families. These data demonstrate that isoform 1, containing
      the large N-terminal extension, is also necessary for normal hearing.

PMID- 17546646
TI  - Expression of coxsackie and adenovirus receptor reduces the lung metastatic
      potential of murine tumor cells.
AB  - The coxsackie and adenovirus receptor (CAR) is involved in the epithelial cell
      tight junction, the downregulated expression of which is observed in different
      cancer types. In the present study, we examined CAR's role in tumor metastasis
      using a B16 melanoma and CT26 colon adenocarcinoma model of experimental
      metastasis. In lung metastasis, the colony number of B16 cells stably expressing
      CAR (B16CAR) was significantly lower than that of the control CAR-negative B16
      cells. B16 and CT26 cells transiently expressing CAR, which were transduced with
      adenovirus (Ad) vector expressing CAR, also reduced lung metastasis, suggesting
      that CAR plays a role in the early stage of metastasis. CAR expression
      significantly decreased the accumulation of B16 cells in the lung after i.v.
      injection and the migration in vitro. CAR expression reduced expression of
      alpha(v), alpha(4), beta(3) and beta(1) integrin, which play important roles in
      attachment to cells or basement membrane. Thus, CAR expression likely acts as a
      metastatic suppressor.

PMID- 17546647
TI  - SEPT9 sequence alternations causing hereditary neuralgic amyotrophy are
      associated with altered interactions with SEPT4/SEPT11 and resistance to
      Rho/Rhotekin-signaling.
AB  - SEPT9 is a member of the cytoskeleton-related septin family, which is highly
      expressed in glia cells in neuronal tissues. Sequence alterations in SEPT9 are
      known to cause hereditary neuralgic amyotrophy (HNA) but precise cellular
      consequences have yet to be determined. Since SEPT9 is thought to function
      through interaction with other septins and small GTPase Rho-mediated signaling,
      we analyzed the properties of HNA-associated SEPT9 missense variants, SEPT9F
      (c.278C>T/p.Ser93Phe in SEPT9_v3; NM_006640.3) and SEPT9W (c.262C>T/p.Arg88Trp in
      SEPT9_v3). We found both sequence variants, but not the wild type, to form
      filaments with SEPT4 along stress fibers in mesenchymal mouse mammary gland NMuMG
      cells. In the epithelial cells, the variants, but not the wild type, were
      colocalized with SEPT11 at cell-cell junctions. In addition, although septin
      filaments containing SEPT9_v3 were disrupted by Rho/Rhotekin signaling, this was
      not the case with SEPT9F and SEPT9W. Sequence variations in SEPT9 causing HNA are
      thus likely to alter modes of interaction with partner molecules in cells, and
      consequently contribute to the pathogenesis of HNA.

PMID- 17546648
TI  - A multiplexed post-translational modification monitoring approach on a matrix
      assisted laser desorption/ionization time-of-flight/time-of-flight mass
      spectrometer.
AB  - Post-translational modifications (PTMs) of proteins are essential for proper
      function, as they regulate many aspects of a protein's activity and interaction
      with substrates. When analyzing modified peptides derived from such proteins by
      mass spectrometry, these modifications can dissociate, producing either a marker
      ion or neutral loss characteristic of the modification, which have conventionally
      been monitored with a precursor ion scan or neutral loss scan, respectively.
      Although powerful, both precursor ion scans and neutral loss scans can only
      screen for one particular modification at a time. This has led to the development
      of multiple neutral loss monitoring (MNM) for neutral losses and multiple
      precursor ion monitoring (MPM) for marker ions on electrospray instruments. Here,
      we report their implementation on a matrix-assisted laser desorption/ionization
      (MALDI) instrument as well as the inception of a novel scan strategy termed
      targeted multiple precursor ion monitoring (tMPM). This latter scan strategy has
      been developed on a MALDI tandem time-of-flight (TOF/TOF) mass spectrometer for
      the identification of multiple PTMs via their associated marker ions by
      manipulating certain components of the instrument, notably the timed ion selector
      and the delayed extraction source 2. Targeted MPM combined with a second
      approach, multiple neutral loss monitoring (MNM), is shown to be a successful
      approach in the identification of PTMs, identifying multiple modified peptides in
      a complex sample matrix.

PMID- 17546649
TI  - Laser desorption/ionization mass spectrometry on porous silicon for metabolome
      analyses: influence of surface oxidation.
AB  - Laser desorption/ionization mass spectrometry (LDI-MS) on porous silicon is a
      promising analytical strategy for the rapid detection of metabolites in
      biological matrices. We show that both oxidized and unoxidized porous silicon
      surfaces are useful in detecting protonated/deprotonated molecules from compounds
      when analyzed in mixtures. We demonstrate the feasibility of using this technique
      for the simultaneous detection of multiple analytes using a synthetic cocktail of
      30 compounds commonly associated with prokaryotic and eukaryotic primary
      metabolism. The predominantly detected species were the protonated molecules or
      their sodium/potassium adducts in the positive-ion mode and the deprotonated
      molecules in the negative-ion mode, as opposed to fragments or other adducts.
      Surface oxidation appears to influence mass spectral responses; in particular, in
      the mixture we studied, the signal intensities of the hydrophobic amino acids
      were noticeably reduced. We show that whilst quantitative changes in individual
      analytes can be detected, ion suppression effects interfere when analyte levels
      are altered significantly. However, the response of most analytes was relatively
      unaffected by changes in the concentration of one of the analytes, so long as it
      was not allowed to dominate the mixture, which may limit the dynamic range of
      this approach. The differences in the response of the analytes when analyzed in
      mixtures could not be accounted for by considering their gas-phase and aqueous
      basicities alone. The implications of these findings in using the technique for
      metabolome analyses are discussed.

PMID- 17546650
TI  - Quantitative detection of metabolites using matrix-assisted laser
      desorption/ionization mass spectrometry with 9-aminoacridine as the matrix.
AB  - Quantitative detection of metabolites is a highly desirable feature in metabolome
      analyses. Recently, the successful detection of multiple metabolites using matrix
      assisted laser desorption/ionization mass spectrometry (MALDI-MS) in the negative
      ion mode employing 9-aminoacridine as the organic matrix was reported (Edwards
      JL, Kennedy RT. Anal. Chem. 2005; 77: 2201-2209). However, there is little
      information available on quantitative detection of multiple metabolites using
      MALDI-MS and in particular the influence changes in metabolite levels have on
      such detections. We investigated this aspect by spiking a synthetic metabolite
      cocktail (consisting of 39 metabolites including amino acids, organic acids and
      phospho-metabolites) with five representative metabolites at increasing
      concentrations, one metabolite at a time, and assessed the signals from replicate
      determinations. It was possible to detect quantitative changes in the spiked
      metabolites. Although analyte suppression was observed, it was possible to
      observe scenarios where the spiked metabolite had little or no influence on the
      quantitative detection of some metabolites. It appears that the mass spectral
      response of the metabolite is suppressed only when the spiked chemical species
      are relatively similar in chemical terms. This suggests that quantitation is
      possible in scenarios where changes in a specific metabolite or a class of
      metabolites are monitored following appropriate analyte separation strategies,
      and that careful interpretations must be made when using the technique for
      quantitative analysis in unbiased metabolomic approaches.

PMID- 17546651
TI  - Determination of three natural pesticides in processed fruit and vegetables using
      high-performance liquid chromatography/tandem mass spectrometry.
AB  - This paper describes a method for the sensitive and selective determination of
      two macrocyclic lactones (abamectin and spinosad) and azadirachtin in apple
      puree, concentrated lemon juice, tomato puree and canned peas. The general sample
      extraction-partitioning method for our gas chromatography and liquid
      chromatography multiresidue methods has been used. The analytical procedure
      involves an extraction with acetone and liquid-liquid partitioning with ethyl
      acetate/cyclohexane combined in one step. The extracts are analyzed by liquid
      chromatography/electrospray ionization tandem mass spectrometry (LC/ESI-MS/MS)
      without any further clean-up step. The pesticides are separated on a reversed
      phase C12 column using a gradient elution. Thirteen simultaneous MS/MS
      transitions of precursor ions were monitored. Studies at fortification levels of
      2.5-10 microg/kg and 25-100 microg/kg gave mean recoveries ranging from 70-100%
      for all compounds with satisfactory precision (relative standard deviation (RSD)
      from 3-20%). The excellent selectivity and sensitivity allows quantification and
      identification of low levels of pesticides in canned peas, tomato and apple
      purees (limits of quantitation (LOQs) 1-5 microg/kg) and in concentrated lemon
      juice (LOQs 2-10 microg/kg). The quantification of analytes was carried out using
      the most sensitive transition for every compound and by 'matrix-matched'
      standards calibration.

PMID- 17546652
TI  - CNS malformations in Knobloch syndrome with splice mutation in COL18A1 gene.

PMID- 17546653
TI  - Development of a sensitive and specific liquid chromatography/mass spectrometry
      method for the determination of tenofovir in human plasma.
AB  - A sensitive and specific method for the quantitation of tenofovir (TFV) in human
      plasma by liquid chromatography/electrospray ionization mass spectrometry was
      developed and validated. Plasma samples were prepared by solid-phase extraction
      performed on Waters Oasis cation-exchange cartridges (30 mg). Chromatographic
      separation was performed isocratically on a reversed-phase Waters Atlantis dC18
      column (2.0x100 mm, 3 microm). The mobile phase consisted of a
      hydroxylamine/acetic acid buffer (pH 6.75) and methanol (93:7, v/v). The
      acquisition was performed in selected ion monitoring mode for the protonated
      molecular ions [M+H]+ of m/z 288.2 for TFV and 212.2 for the internal standard,
      zalcitibine. The method was fully validated to determine its specificity,
      recovery, linearity and sensitivity, accuracy and precision. The analytical range
      was set at 1-750 ng/mL using a 200 microL plasma sample, with a mean coefficient
      of determination (r2) of 0.9969. The mean accuracies for the calibration
      standards ranged from -5.0 to 4.3%, while the precisions were within 1.2 and
      6.4%. Intra-assay and inter-assay mean accuracies for three quality control
      concentrations (2, 60, and 600 ng/mL) ranged from -6.1 to 10.7%, while the
      precisions were within 1.3 and 9.1%. TFV was shown to be stable under normal
      storage and assay conditions; no degradation was seen when stored at -20 degrees
      C or -80 degrees C for up to 6 months, and after 16 h at room temperature in the
      injection matrix. The present method provides an accurate, precise, and sensitive
      tool for TFV quantitation and was successfully applied to an external proficiency
      testing program and pharmacokinetic analysis.

PMID- 17546654
TI  - Polyaniline-coated nanoelectrospray emitters treated with hydrophobic polymers at
      the tip.
AB  - In nanoelectrospray ionization (nanoESI) techniques, the hydrophilic character of
      the emitters generally produces large bases for the Taylor cones, thereby
      generating relatively large droplet sizes and consequently reduced sensitivity.
      In order to minimize this 'wetting' effect in nanoESI, a model hydrophobic
      polymer (an acrylic paint) was coated at the tip of commercial polyaniline (PANI)
      coated emitters, and their performance was compared with that of unmodified PANI
      emitters using oxytocin and neuropeptide Y (NPY) solutions. In experiments with
      oxytocin, the hydrophobic emitter produced higher signal intensities (up to 3.6
      times) as well as higher signal-to-noise ratios (33% increase) than those from
      the unmodified PANI emitter. In addition, the hydrophobic emitter showed
      reusability and a slightly wider linear dynamic range (10 nM to 50 microM,
      r2=0.9938) than that from the unmodified PANI emitter (10 nM to 10 microM,
      r2=0.9904). In the case of NPY, the hydrophobic emitter also enabled an
      approximately 350-fold overall increase in sensitivity than the unmodified PANI
      emitter (70 zmol vs. 25 amol). The enhanced performance of the hydrophobic
      emitter clearly indicates potential for further increases in nanoESI sensitivity
      using emitters with tailored hydrophobic overcoatings.

PMID- 17546655
TI  - PRG4 exchange between the articular cartilage surface and synovial fluid.
AB  - The boundary lubrication function of articular cartilage is mediated in part by
      proteoglycan 4 (PRG4) molecules, found both in synovial fluid (SF) and bound to
      the articular cartilage surface. Currently the mechanism by which PRG4 binds to
      the articular surface is not well understood. The objectives of this study were
      to determine (1) the effect of bathing fluid contents on PRG4 concentration at
      the articular surface ([PRG4](cart)), and (2) whether native PRG4 can be removed
      from the surface and subsequently repleted with PRG4 from synovial fluid. In one
      experiment, cylindrical cartilage disks were stored in solutions of various PRG4
      concentrations, either in phosphate-buffered saline (PBS) or SF as the carrier
      fluid. In a separate experiment, cartilage disks were stored in solutions
      expected to remove native PRG4 from the articular surface and allow subsequent
      repletion with PRG4 from SF. [PRG4](cart) was independent of PRG4 concentration
      of the bathing fluid, and was similar for both carrier fluids. PRG4 was removed
      from cartilage by treatment with hyaluronidase, reduction/alkylation, and sodium
      dodecyl sulphate, and was repleted fully by subsequent bathing in SF. These
      results suggest that the articular surface is normally saturated with tightly
      bound PRG4, but this PRG4 can exchange with the PRG4 in SF under certain
      conditions. This finding suggests that all tissues surrounding the joint cavity
      that secrete PRG4 into the SF may help to maintain lubrication function at the
      articular surface.

PMID- 17546656
TI  - Implementing molecular connectivity theory, a basic tool in modeling drugs.
AB  - The concepts of chain graph, general graph, and complete graph have been used to
      implement the graph framework of molecular connectivity (MC) theory. Some
      concepts of this theory have been addressed using "external" theoretical concepts
      belonging mostly to quantum or structural chemistry, with no direct counterpart
      in graph theory. Thus, while the concept of chain graph can be used to tackle the
      cis-trans isomerism problem, the concept of pseudograph, or general graph can be
      used to tackle the description of the sigma-, pi-, and nonbonding n-electrons.
      The concept of complete graph can instead be used to tackle the electron core
      problem of the atoms of a molecule. Graph concepts can also be used to tackle the
      problem of the hydrogen contribution in hydrogen depleted graphs, which are
      encoded by the aid of a perturbation parameter, which differentiates between
      compounds with similar hydrogen-suppressed chemical graphs, like the graphs of
      CH(3)F and BH(2)F. These concepts have allowed redesign of a central parameter of
      MC theory, the valence delta, giving MC indices with improved model quality as
      exemplified here with different properties for each treated topic.

PMID- 17546657
TI  - Determination of the elemental composition of trace analytes in complex matrices
      using exact masses of product ions and corresponding neutral losses.
AB  - The emergence of time-of-flight (TOF) and hybrid quadrupole/time-of-flight (Q
      TOF) mass spectrometers has offered new possibilities for determining the
      elemental composition of analytes present at trace levels. The mass accuracy
      provided by these instruments is currently in the range of 2-5 m m/z units,
      permitting the determination of the elemental composition of small molecules. The
      orthogonal information of relative isotopic abundances (RIAs) is used to reduce
      the number of elemental compositions that are possible, based on consideration of
      exact masses. Elimination of additional possible compositions has been reported
      when the analyte is fragmented and its resulting product ions and corresponding
      neutral losses are carefully analyzed. Published algorithms reduce the number of
      proposed precursor ions by deleting each precursor candidate which cannot be
      explained by summing any combination of postulated product ion and corresponding
      neutral loss elemental composition candidates. An extension of such algorithms is
      described in this paper. This approach compares not only the precursor ion with
      the different fragments, but tests the possible descent of any ion from all other
      recorded ions. This extended algorithm has been tested by processing published
      data. Algorithms analyzing product ion spectra can be used for real-life data.
      However, there is a risk that an ion which originates from the mobile phase or
      from a co-eluting matrix compound can be mathematically correlated to the
      investigated precursor ion. Such an incorrect correlation can lead to the
      deletion of a correct elemental composition. This is an important issue if TOF
      rather than Q-TOF instruments are used. Therefore, ultra-performance liquid
      chromatography (UPLC) and a peak deconvolution algorithm were used to generate
      and process TOF chromatograms in order to minimize the number of ions which are
      not related to the analyte precursor ion. The combined use of chromatographic
      deconvolution and product ion spectra has been tested and is critically
      discussed.

PMID- 17546658
TI  - Matrix-assisted laser desorption/ionization mass spectrometry of polysaccharides
      with 2',4',6'-trihydroxyacetophenone as matrix.
AB  - So far, there have been only a few matrices reported for detection of
      polysaccharides with molecular weight higher than 3000 Daltons by matrix-assisted
      laser desorption/ionization mass spectrometry (MALDI-MS). In this work, we found
      that 2',4',6'-trihydroxyacetophenone (THAP) is a good matrix for MALDI time-of
      flight MS analysis of polysaccharides with broad mass range. Large
      polysaccharides, dextrans, glycoproteins and polysialic acids have been
      successfully detected by MALDI-MS with THAP as matrix.

PMID- 17546659
TI  - The crystal structure of the catalytic domain of the chick retinal neurite
      inhibitor-receptor protein tyrosine phosphatase CRYP-2/cPTPRO.

PMID- 17546660
TI  - Hot spots--a review of the protein-protein interface determinant amino-acid
      residues.
AB  - Proteins tendency to bind to one another in a highly specific manner forming
      stable complexes is fundamental to all biological processes. A better
      understanding of complex formation has many practical applications, which include
      the rational design of new therapeutic agents, and the analysis of metabolic and
      signal transduction networks. Alanine-scanning mutagenesis made possible the
      detection of the functional epitopes, and demonstrated that most of the protein
      protein binding energy is related only to a group of few amino acids at
      intermolecular protein interfaces: the hot spots. The scope of this review is to
      summarize all the available information regarding hot spots for a better atomic
      understanding of their structure and function. The ultimate objective is to
      improve the rational design of complexes of high affinity and specificity as well
      as that of small molecules, which can mimic the functional epitopes of the
      proteic complexes.

PMID- 17546661
TI  - XC5848, an ORFan protein from Xanthomonas campestris, adopts a novel variant of
      Sm-like motif.

PMID- 17546662
TI  - Redox properties and evolution of human glutaredoxins.
AB  - Glutaredoxins (Grxs) are glutathione-dependent oxidoreductases that belong to the
      thioredoxin superfamily catalyzing thiol-disulfide exchange reactions via active
      site cysteine residues. Focusing on the human dithiol glutaredoxins having a C-X
      Y-C active site sequence motif, the redox potentials of hGrx1 and hGrx2 were
      determined to be -232 and -221 mV, respectively, using a combination of redox
      buffers, protein-protein equilibrium and thermodynamic linkage. In addition, a
      nonactive site disulfide was identified between Cys28 and Cys113 in hGrx2 using
      redox buffers and chemical digestion. This disulfide confers nearly five kcal
      mol(-1) additional stability by linking the C-terminal helix to the bulk of the
      protein. The redox potential of this nonactive site disulfide was determined to
      be -317 mV and is thus expected to be present in all but the most reducing
      conditions in vivo. As all human glutaredoxins contain additional nonactive site
      cysteine residues, a full phylogenetic analysis was performed to help elucidate
      their structural and functional roles. Three distinct groups were found: Grx1,
      Grx2, and Grx5, the latter representing a highly conserved group of monothiol
      glutaredoxins having a C-G-F-S active site sequence, with clear homologs from
      bacteria to human. Grx1 and Grx2 diverged from a common ancestor before the
      origin of vertebrates, possibly even earlier in animal evolution. The highly
      stabilizing nonactive site disulfide observed in hGrx2 is found to be a conserved
      feature within the deuterostomes and appears to be the only additional conserved
      intramolecular disulfide within the glutaredoxins.

PMID- 17546663
TI  - Carnosine interaction with nitric oxide and astroglial cell protection.
AB  - The neuropeptide carnosine (beta-amyloid peptide aggregation has been
      demonstrated. Carnosine protection against peroxynitrite damage is particularly
      relevant, but until now there has been no evidence of any direct interaction with
      nitric oxide. In this study we examined the protection that carnosine provides
      against nitric oxide (NO)-induced cell death in primary rat astroglial cell
      cultures treated with lipopolysaccharide (LPS) and interferon gamma (INFgamma), a
      well-known neurotoxic proinflammatory condition. A correlation was found between
      cell protection and NO free-radical scavenging activity of carnosine. Moreover,
      by competitive spectrophotometric measurement and electrospray mass spectrometry
      analysis in cell-free experiments, we demonstrated a direct interaction of the
      dipeptide with NO. A comparison of carnosine with its homologues or derivatives
      (homocarnosine and carcinine) as well as with its amino acid constituents (L
      histidine and beta-alanine) highlighted that only histidine showed significant
      scavenging activity. Therefore, carnosine shows direct NO-trapping ability and
      may be a valuable multifunctional molecule in the treatment of neurodegenerative
      disorders.

PMID- 17546665
TI  - pH-dependent interactions of indinavir and lipids in nanoparticles and their
      ability to entrap a solute.
AB  - We have investigated the ability of lipid-indinavir particles composed of 3-to-1
      lipid-drug molar ratio to encapsulate an aqueous marker calcein and anti-HIV drug
      (3)H-phosphonylmethoxypropyl-adenine (PMPA). Even at a high density of indinavir
      associated to lipid-indinavir nanoparticles, they form an enclosed lipid membrane
      that allows encapsulation of calcein and PMPA in an aqueous compartment. At
      neutral pH, practically all indinavir was incorporated into lipid bilayer and
      lipid associated indinavir can be dissociated with half-maximum pH recorded
      between 5.2 and 5.5. pH-Dependent release of indinavir did not influence calcein
      release significantly. However, pH-dependent release of indinavir affected PMPA
      release. By lowering pH, PMPA release was enhanced in the presence of indinavir
      in the lipid bilayer. Collectively, these data indicate that indinavir
      incorporated in lipid particles provides (1) stable bilayers capable of
      encapsulating other hydrophilic drugs, (2) ability to dissociate indinavir (which
      is acid stable) from lipid membranes, by lowering the pH, and (3) enabling
      enhancement in pH-dependent release of aqueous contents. However, the degree of
      pH-dependent release could be related to the charge and size of an aqueous
      molecule.

PMID- 17546666
TI  - Near infrared spectroscopy of magnesium stearate hydrates and multivariate
      calibration of pseudopolymorph composition.
AB  - Samples of magnesium stearate monohydrate and dihydrate were used to prepare
      standard mixtures of known pseudopolymorphic composition. Near infrared spectra
      (NIR) of the standard mixtures were measured to develop multivariate calibration
      models for the pseudopolymorphic composition of magnesium stearate by partial
      least squares (PLS) regression. Magnesium stearate hydrate compositions of the
      standard mixtures were compared against the hydrate composition based on
      thermogravimetric analysis (TGA). The mixture compositions determined from TGA
      mass loss on drying (LOD) measurements were found to be inaccurate. PLS
      regression was applied to the TGA thermograms of the standard mixtures to
      generate more accurate reference values, and this model was then applied to a set
      of validation samples. Application of the NIR PLS model to the validation sample
      set resulted in precise estimates of sample pseudopolymorphic composition when
      compared to the TGA PLS reference values. The NIR PLS model was found to be more
      sensitive than TGA LOD to small quantities of hydrates, and the TGA PLS model was
      also found to be more sensitive that TGA LOD. The results demonstrate the
      challenges and opportunities that arise when rapid, nondestructive spectroscopic
      methods depend on insensitive or inaccurate reference methods for development of
      multivariate calibration models.

PMID- 17546667
TI  - Mesoporous silicon in drug delivery applications.
AB  - During the last few years, a number of interesting drug delivery applications of
      mesoporous materials have been demonstrated. Mesoporous silicon has many
      important properties advantageous to drug delivery applications. The small size
      of the pores confines the space of a drug and engages the effects of surface
      interactions of the drug molecules and the pore wall. The size of the pores and
      the surface chemistry of the pore walls may be easily changed and controlled.
      Depending on the size and the surface chemistry of the pores, increased or
      sustained release of the loaded drug can be obtained. Drug loading from a
      solution at room temperature enables the use of porous silicon (PSi) also with
      sensitive therapeutic compounds susceptible to degradation, like peptides and
      proteins. This article reviews the fabrication and chemical modifications of PSi
      for biomedical applications, and also the potential advantages of PSi in drug
      delivery.

PMID- 17546668
TI  - Increased risk of essential tremor in first-degree relatives of patients with
      Parkinson's disease.
AB  - We conducted a historical cohort study of 981 first-degree relatives of 162
      patients with Parkinson's disease (PD) and of 838 first-degree relatives of 147
      controls representative of the population of Olmsted County, Minnesota. In
      addition, we studied 2,684 first-degree relatives of 411 patients with PD
      referred to the Mayo Clinic. Relatives were interviewed and screened for tremor
      either directly or through a proxy, and those who screened positive were examined
      or copies of their medical records were obtained to confirm the diagnosis of
      essential tremor (ET). We also obtained ET information from a medical records
      linkage system (family study method). In the population-based sample, the risk of
      ET was significantly increased for relatives of patients with onset of PD<or=66
      years (first tertile; hazard ratio [HR]=2.24; 95% confidence interval [95%
      CI]=1.26-3.98; P=0.006). In the referral-based sample, the risk of ET among
      relatives increased with younger onset of PD in patients (linear trend; P=0.001),
      and was higher in relatives of PD patients with the tremor-predominant or mixed
      form when compared with relatives of patients with the akinetic-rigid form, and
      in men compared with women. These findings suggest that PD and ET may share
      familial susceptibility factors.

PMID- 17546669
TI  - Prevalence of nonmotor symptoms in Parkinson's disease in an international
      setting; study using nonmotor symptoms questionnaire in 545 patients.
AB  - 2006, there was, no single instrument (questionnaire or scale) for attempting a
      comprehensive assessment of the wide range of nonmotor symptoms (NMS) of
      Parkinson's disease (PD). The PD nonmotor group, a multidisciplinary group of
      experts including patient group representatives developed and validated the NMS
      screening questionnaire (NMSQuest) comprising 30 items. The NMSQuest is a self
      completed screening tool designed to draw attention to the presence of NMS. In
      this paper, we present the results gathered from 545 patients using the
      definitive version of the NMSQuest highlighting the prevalence of the wide range
      of NMS flagged in the NMSQuest from consecutive PD patients in an international
      setting.

PMID- 17546670
TI  - Cardiomyopathy in Friedreich's ataxia-assessment by cardiac MRI.
AB  - Cardiomyopathy is an important and frequently life limiting manifestation of
      Friedreich's ataxia (FA), the most prevalent form of autosomal recessive ataxia.
      Left ventricular mass is used as primary outcome measure in recent intervention
      studies but systematic analyses of FA cardiomyopathy are sparse. To assess
      cardiac hypertrophy by cardiac magnetic resonance imaging (MRI) in vivo, we
      assessed 41 adult patients with genetically confirmed FA and 33 age- and sex
      matched healthy controls by cardiac MRI and echocardiogarphy. Septal hypertrophy
      and left ventricular mass index were determined by two independent raters. MRI
      revealed hypertrophy of the interventricular septum in 40% and increased left
      ventricular mass index in 29% of patients. Interobserver variability was less
      than 5% for both measures. GAA repeat length had only minor influence on
      interventricular septum thickness. Left ventricular mass index decreased with
      age. Severity of ataxia did not correlate with cardiac disease. In
      echocardiography wall diameter was assessable only in 31 of 41 FA patients with
      32% of patients presenting septal hypertrophy and 6% increased left ventricular
      mass index. We conclude that cardiac hypertrophy is present only in a minority of
      adult FA patients. If despite this limitation intervention studies use left
      ventricular mass as outcome measure, MRI is recommended as the most accurate
      assessment of cardiac anatomy in vivo.

PMID- 17546671
TI  - Dynamics of heteropentameric nicotinic acetylcholine receptor: implications of
      the gating mechanism.
AB  - The dynamics characteristics of the currently available structure of Torpedo
      nicotinic acetylcholine receptor (nAChR), including the extracellular,
      transmembrane, and intracellular domains (ICDs), were analyzed using the Gaussian
      Network Model (GNM) and Anisotropic Network Model (ANM). We found that a
      symmetric quaternary twist motion, reported previously in the literature in a
      homopentameric receptor (Cheng et al. J Mol Biol 2006;355:310-324; Taly et al.
      Biophys J 2005;88:3954-3965), occurred also in the heteropentameric Torpedo
      nAChR. We believe, however, that the symmetric twist alone is not sufficient to
      explain a large body of experimental data indicating asymmetry and subunit
      nonequivalence during gating. Here we report our results supporting the
      hypothesis that a combination of symmetric and asymmetric motions opens the gate.
      We show that the asymmetric motion involves tilting of the TM2 helices.
      Furthermore, our study reveals three additional aspects of channel dynamics: (1)
      loop A serves as an allosteric mediator between the ligand binding loops and
      those at the domain interface, particularly the linker between TM2 and TM3; (2)
      the ICD can modulate the pore dynamics and thus should not be neglected in gating
      studies; and (3) the F loops, which are peculiarly longer and poorly-conserved in
      non-alpha-subunits, have important dynamical implications.

PMID- 17546673
TI  - RLS, PLM, and their differential diagnosis--a video guide.
AB  - This video guide has been designed as an introduction to the full spectrum of
      nocturnal presentations of restless legs syndrome (RLS) and periodic limb
      movements (PLM), and to their differential diagnoses. The DVD consists of four
      sections: In the first part, clinical presentations of RLS are covered (videos 1
      3). In the second part, the variety of typical and less frequent presentations of
      PLM are demonstrated (videos 4-14). The third part shows the clinical
      presentation of augmentation (videos 15-19). The last section is dedicated to the
      differential diagnosis of RLS and PLM and demonstrates nocturnal manifestations
      of other motor disorders during sleep, which must be distinguished: Epilepsy,
      parasomnias, and other movement disorders (of sleep) (videos 20-33). After
      viewing this DVD, the reader should be able to: (1) appreciate the spectrum of
      voluntary and unvoluntary movements seen in patients with RLS during wakefulness;
      (2) recognize typical PLM during sleep in subjects with RLS, and appreciate the
      enormous variability of clinical presentations of PLM; (3) describe specific and
      distinct aspects of motor activity in augmentation in patients with RLS; and (4)
      be aware of the most important differential diagnosis of RLS/PLM from a video or
      nocturnal motor activity point of view, namely, nocturnal epilepsy, parasomnias,
      and others.

PMID- 17546672
TI  - Crystal structure of homoserine O-succinyltransferase from Bacillus cereus at 2.4
      A resolution.

PMID- 17546674
TI  - Effect of age on geriatric depression scale performance in Parkinson's disease.
AB  - The purpose of this study was to compare the validity of the 15-item Geriatric
      Depression Scale (GDS-15) in nonelderly (<65 years), young-elderly (age, 65-75),
      and old-elderly (>75 years) patients with Parkinson's disease (PD). 57
      nonelderly, 88 young-elderly, and 81 old-elderly PD patients were administered
      the GDS-15 and the Structured Clinical Interview for DSM-IV depression module.
      Receiver-operating characteristic (ROC) curves were plotted for GDS-15 scores
      against a DSM-IV diagnosis of major or minor depression. The discriminant
      validity of the GDS-15 was high for nonelderly, young-elderly, and old-elderly
      subjects (ROC area under curve = 0.92, 0.91, and 0.95, respectively), with
      optimal dichotomization at a cut-off of 4/5 (85% sensitivity and 84% specificity
      in nonelderly; 89% sensitivity and 82% specificity in young-elderly) and 5/6 (90%
      sensitivity and 90% specificity in old-elderly). In conclusion, the GDS-15 has
      comparable validity in younger and older PD patients, suggesting its
      appropriateness as a depression screening instrument in PD patients of all ages.

PMID- 17546675
TI  - Cavendish's crocodile and dark horse: the lives of Rutherford and Aston in
      parallel.
AB  - Ernest Rutherford and Francis Aston were born a world apart but both would become
      two of the most influential physicists of their time. Their separate training,
      under the direction of J.J. Thomson at the Cavendish Laboratory, shaped their
      future and allowed both men to develop and apply their considerable skills in
      experimental physics. It also catalyzed their careers and ultimately led to each
      receiving a Nobel Prize. Although they had very different characters, Rutherford
      and Aston became close colleagues and confidants who spent considerable time
      together within the confines of the Cavendish Laboratory, at Trinity College, and
      elsewhere in Cambridge. They also traveled the world in company, usually as part
      of a group or British delegation of scientists attending conferences and meetings
      overseas. This article parallels the lives of the two men. It describes how they
      came to work at the Cavendish, their scientific accomplishments and accolades,
      and their activities and interactions away from the laboratory.

PMID- 17546676
TI  - New all-atom force field for molecular dynamics simulation of an AlPO(4)-34
      molecular sieve.
AB  - A force field of the triclinic framework of AlPO(4)-34, important in methanol
      hydrocarbon conversion reactions, was developed using an empirical potential
      function. Molecular dynamics simulation of an AlPO(4)-34 triclinic framework
      segment of 1216 atoms, containing the template molecules isopropylamine and
      water, was performed with explicit consideration of atomic charges. The average
      RMS difference between instantaneous positions of the framework atoms during 1 ns
      simulation and their positions in the structure determined from single crystal X
      ray diffraction was calculated, and the average structure of the flexible
      framework was determined. The computed Debye-Waller factors and simulated FTIR
      spectra are in good agreement with the experimental data. The new force field
      permits detailed molecular dynamics simulations of flexible, charged
      aluminophosphate molecular sieves which should lead to a better understanding of
      the catalytic processes and the crucial role played by templating molecules.

PMID- 17546677
TI  - Improving the efficiency of the NEB reaction path finding algorithm.
AB  - The nudged elastic band (NEB) method is a successful optimization method for
      obtaining minimum energy reaction paths if only the initial and final structures
      are known. However, the original implementation of the method had some
      limitations, which has meant that there has been considerable interest in
      proposing alternative NEB formulations, which show improved convergence behavior.
      In this work, we present two modifications to the standard NEB procedure. The
      first involves the use of a second-order quasi-Newton optimization technique
      applied separately to each of the images that form the path. The second consists
      of the use of an interpolating spline to represent the path. This ensures that
      the images along the path are evenly spaced and means that the arbitrary spring
      forces employed in the standard NEB method are no longer necessary. We tested
      these modifications on a set of small, but relatively complex, chemical systems
      and found that the computation time was reduced by as much as 90% compared with
      the standard method.

PMID- 17546678
TI  - Lysosomal hydrolases in cerebrospinal fluid from subjects with Parkinson's
      disease.
AB  - Recent studies have shown a genetic association between glucocerebrosidase
      deficiencies and Parkinson's disease (PD). To further explore this issue the
      activity of beta-glucocerebrosidase and the activities of other lysosomal
      enzymes, alpha-mannosidase, beta-mannosidase, beta-hexosaminidase, and beta
      galactosidase have been evaluated in the cerebrospinal fluid (CSF) of PD
      patients. The activities of alpha-mannosidase, beta-mannosidase, beta
      glucocerebrosidase, and beta-hexosaminidase were substantially decreased in the
      CSF of PD patients, while levels of beta-galactosidase were essentially identical
      to controls. This study indicates that in PD several lysosomal hydrolases have
      decreased activities, further supporting a possible link between
      pathophysiological mechanisms underlying PD and lysosomal hydrolases.

PMID- 17546679
TI  - Allopurinol and 6MP: steering through the therapeutic obstacle course.

PMID- 17546680
TI  - Cell cycle alteration and decreased cell proliferation in the hippocampal dentate
      gyrus and in the neocortical germinal matrix of fetuses with Down syndrome and in
      Ts65Dn mice.
AB  - Down syndrome (DS), the leading genetic cause of mental retardation, is
      characterized by reduced number of cortical neurons and brain size. The
      occurrence of these defects starting from early life stages points at altered
      developmental neurogenesis as their major determinant. The goal of our study was
      to obtain comparative evidence for impaired neurogenesis in the hippocampal
      dentate gyrus (DG) of DS fetuses and Ts65Dn mice, an animal model for DS. Cell
      proliferation in human fetuses was evaluated with Ki-67 (a marker of cells in S +
      G(2) + M phases of cell cycle) and cyclin A (a marker of cells in S phase)
      immunohistochemistry. We found that in the DG of DS fetuses the number of
      proliferating cells was notably reduced when compared with controls. A similar
      reduction was observed in the germinal matrix of the lateral ventricle. In both
      structures, DS fetuses showed a reduced ratio between cyclin A- and Ki-67
      positive cells when compared with controls, indicating that they had a reduced
      number of cycling cells in S phase. In the DG of P2 Ts65Dn mice cell
      proliferation, assessed 2 h after an injection of bromodeoxyuridine (BrdU), was
      notably reduced, similarly to DS fetuses. After 28 days, Ts65Dn mice had still
      less BrdU-positive cells than controls. Phenotypic analysis of the surviving
      cells showed that Ts65Dn mice had a percent number of cells with astrocytic
      phenotype larger than controls. Using phospho-histone H3 immunohistochemistry we
      found that both DS fetuses and P2 Ts65Dn mice had a higher number of
      proliferating cells in G(2) and a smaller number of cells in M phase of cell
      cycle. Results provide novel evidence for proliferation impairment in the
      hippocampal DG of the DS fetal brain, comparable to that of the P2 mouse model,
      and suggest that cell cycle alterations may be critical determinants of the
      reduced proliferation potency.

PMID- 17546681
TI  - Perinatal iron deficiency results in altered developmental expression of genes
      mediating energy metabolism and neuronal morphogenesis in hippocampus.
AB  - The human and rat hippocampus is highly susceptible to iron deficiency (ID)
      during the late fetal, early neonatal time period which is a peak time of
      regulated brain iron uptake and utilization. ID during this period alters
      cognitive development and is characterized by distinctive, long-term changes in
      hippocampal cellular growth and function. The fundamental processes underlying
      these changes are not entirely understood. In this study, ID-induced changes in
      expression of 25 genes implicated in iron metabolism, including cell growth and
      energy metabolism, dendrite morphogenesis, and synaptic connectivity were
      assessed from postnatal day (P) 7 to P65 in hippocampus. All 25 genes showed
      altered expression during the period of ID (P7, 15, and 30); 10 had changes on
      P65 after iron repletion. ID caused long-term diminished protein levels of four
      factors critical for hippocampal neuron differentiation and plasticity, including
      CamKII alpha, Fkbp1a (Fkbp12), Dlgh4 (PSD-95), and Vamp1 (Synaptobrevin-1). ID
      altered gene expression in the mammalian target of rapamycin (mTOR) pathway and
      in a gene network implicated in Alzheimer disease etiology. ID during late fetal
      and early postnatal life alters the levels and timing of expression of critical
      genes involved in hippocampal development and function. The study provides
      targets for future studies in elucidating molecular mechanisms underpinning
      iron's role in cognitive development and function.

PMID- 17546682
TI  - Spontaneous navigational strategies and performance in the virtual town.
AB  - The 4-on-8 virtual maze provides evidence for variability in spontaneous strategy
      use during navigation. Functional magnetic resonance imaging (MRI) confirmed that
      these spatial and response strategies rely on the hippocampus and caudate nucleus
      memory systems, respectively. We asked whether the spontaneous use of a
      particular navigational strategy was associated with a particular ability to
      navigate in one's environment. We tested 30 young participants on the 4-on-8
      virtual maze and we assessed their way finding ability in a virtual town. As
      expected, spatial learners performed well in the virtual town and the response
      learners, who never used external landmarks and relied purely on an egocentric
      strategy, performed poorly. Interestingly, a group who used the most efficient
      response strategy based on external landmarks in the 4-on-8 virtual maze,
      switched to the most efficient spatial strategy in the virtual town. Our data
      suggest that the best navigators are those who appropriately use spatial or
      response strategies depending on the demands of the task.

PMID- 17546683
TI  - Contrasting roles of neural firing rate and local field potentials in human
      memory.
AB  - Recording the activity of neurons is a mainstay of animal memory research, while
      human recordings are generally limited to the activity of large ensembles of
      cells. The relationship between ensemble activity and neural firing rate during
      declarative memory processes, however, remains unclear. We recorded neurons and
      local field potentials (LFPs) simultaneously from the same sites in the human
      hippocampus and entorhinal cortex (ERC) in patients with implanted intracranial
      electrodes during a virtual taxi-driver task that also included a memory
      retrieval component. Neurons increased their firing rate in response to specific
      passengers or landmarks both during navigation and retrieval. Although we did not
      find item specificity in the broadband LFP, both theta- and gamma-band LFPs
      increased power to specific items on a small but significant percent of channels.
      These responses, however, did not correlate with item-specific neural responses.
      To contrast item-specific responses with process-specific responses during
      memory, we compared neural and LFP responses during encoding (navigation) and
      retrieval (associative and item-specific recognition). A subset of neurons also
      altered firing rates nonspecifically while subjects viewed items during encoding.
      Interestingly, LFPs in the hippocampus and ERC increased in power nonspecifically
      while subjects viewed items during retrieval, more often during associative than
      item-recognition. Furthermore, we found no correlation between neural firing rate
      and broadband, theta-band, and gamma-band LFPs during process-specific responses.
      Our findings suggest that neuronal firing and ensemble activity can be
      dissociated during encoding, item-maintenance, and retrieval in the human
      hippocampal area, likely relating to functional properties unique to this region.

PMID- 17546684
TI  - Effect of PEG modification on subtilisin Carlsberg activity, enantioselectivity,
      and structural dynamics in 1,4-dioxane.
AB  - The employment of enzymes as catalysts within organic media has traditionally
      been hampered by the reduced enzymatic activities when compared to catalysis in
      aqueous solution. Although several complementary hypotheses have provided
      mechanistic insights into the causes of diminished activity, further development
      of biocatalysts would greatly benefit from effective chemical strategies (e.g.,
      PEGylation) to ameliorate this event. Herein we explore the effects of altering
      the solvent composition from aqueous buffer to 1,4-dioxane on structural,
      dynamical, and catalytic properties of the model enzyme subtilisin Carlsberg
      (SBc). Furthermore, we also investigate the effects of dissolving the enzyme in
      1,4-dioxane through chemical modification with poly(ethylene)-glycol (PEG, M(W) =
      20 kDa) on these enzyme properties. In 1,4-dioxane a 10(4)-fold decrease in the
      enzyme's catalytic activity was observed for the hydrolysis reaction of vinyl
      butyrate with D(2)O and a 50% decrease in enzyme structural dynamics as evidenced
      by reduced amide H/D exchange kinetics occurred. Attaching increasing amounts of
      PEG to the enzyme reversed some of the activity loss. Evaluation of the
      structural dynamic behavior of the PEGylated enzyme within the organic solvent
      revealed an increase in structural dynamics at increased PEGylation. Correlation
      analysis between the catalytic and structural dynamic parameters revealed that
      the enzyme's catalytic activity and enantioselectivity depended on the changes in
      protein structural dynamics within 1,4-dioxane. These results demonstrate the
      importance of protein structural dynamics towards regulating the catalytic
      behavior of enzymes within organic media.

PMID- 17546685
TI  - Cell-free synthesis and maturation of [FeFe] hydrogenases.
AB  - [FeFe] hydrogenases catalyze the reversible reduction of protons to molecular
      hydrogen (Adams (1990); Biochim Biophys Acta 1020(2): 115-145) and are of
      significant interest for the biological production of hydrogen fuel. They are
      complex proteins with active sites containing iron, sulfur, and carbon monoxide
      and cyanide ligands (Peters et al. (1998); Science 282(5395): 1853-1858).
      Maturation enzymes for [FeFe] hydrogenases have been identified (Posewitz et al.
      (2004); J Biol Chem 279(24): 25711-25720), but complete mechanisms have not yet
      been elucidated. The study of [FeFe] hydrogenases has been impeded by the lack of
      an easily manipulated expression/activation system capable of producing these
      complex and extremely oxygen-sensitive enzymes. Here we show the first expression
      of functional [FeFe] hydrogenases in an Escherichia coli-based cell-free
      transcription/translation system. We have produced and matured both algal and
      bacterial hydrogenases using E. coli cell extracts containing the HydG, HydE, and
      HydF proteins from Shewanella oneidensis. The current system produces
      approximately 22 microg/mL of active protein, constituting approximately 44% of
      the total protein produced. Active protein yield is greatly enhanced by pre
      incubation of the maturation enzyme-containing extract with inorganic iron and
      sulfur for reconstitution of the [Fe-S] clusters in HydG, HydE, and HydF. The
      absence of cell walls permits direct addition of cofactors and substrates,
      enabling rapid production of active protein and providing control over the
      maturation conditions. These new capabilities will enhance the investigation of
      complex proteins requiring helper proteins for maturation and move us closer to
      the development of improved hydrogenases for biological production of hydrogen as
      a clean, renewable alternative fuel.

PMID- 17546686
TI  - HSP70 kinetics study by continuous observation of HSP-GFP fusion protein
      expression on a perfusion heating stage.
AB  - The direct correlation between levels of heat shock protein expression and
      efficiency of its tissue protection function motivates this study of how thermal
      doses can be used for an optimal stress protocol design. Heat shock protein 70
      (HSP70) expression kinetics were visualized continuously in cultured bovine
      aortic endothelial cells (BAECs) on a microscope heating stage using green
      fluorescent protein (GFP) as a reporter. BAECs were transfected with a DNA
      vector, HSP(p)-HSP70-GFP which expresses an HSP70-GFP fusion protein under
      control of the HSP70 promoter. Expression levels were validated by western blot
      analysis. Transfected cells were heated on a controlled temperature microscope
      stage at 42 degrees C for a defined period, then shifted to 37 degrees C for
      varied post-heating times. The expression of HSP70-GFP and its sub-cellular
      localization were visualized via fluorescence microscopy. The progressive
      expression kinetics were measured by quantitative analysis of serial fluorescence
      images captured during heating protocols from 1 to 2 h and post-heating times
      from 0 to 20 h. The results show two sequential peaks in HSP70 expression at
      approximately 3 and 12 h post-heat shock. A progressive translocation of HSP70
      from the cytoplasm to the nucleus was observed from 6 to 16 h. We conclude that
      we have successfully combined molecular cloning and optical imaging to study
      HSP70 expression kinetics. The kinetic profile for HSP70-GFP fusion protein is
      consistent with the endogenous HSP70. Furthermore, information on dynamic
      intracellular translocation of HSP70 was extracted from the same experimental
      data.

PMID- 17546687
TI  - Versatile RHDV virus-like particles: incorporation of antigens by genetic
      modification and chemical conjugation.
AB  - Virus-like particles have proved to be excellent molecular scaffolds, yet the
      individual characteristics and immune responses generated against each VLP
      requires the development of a wide range of capsids for use as vaccines,
      molecular delivery vessels, and nanoscale templates. Here we describe the
      development of Rabbit haemorrhagic disease virus (RHDV)-like particles as a
      rapidly versatile molecular workbench, overcoming limitations imposed by
      established genetic antigen incorporation procedures with chimeric VLP.
      Production of the RHDV capsid protein in a baculovirus system led to the self
      assembly of VLP which were recovered at over 99% purity and manipulated both
      genetically and chemically. Fusion of small peptide sequences to RHDV VLP was
      well tolerated, forming chimeric capsids that enhanced the presentation of
      foreign peptide to hybridoma T helper cells 700-fold. Rapid and simple
      conjugation techniques employing the hetero-bifunctional chemical linker sulfo
      SMCC enabled both small peptides and whole proteins to be conjugated to the
      surface of RHDV VLP, overcoming limitations imposed on VLP formation and yield
      experienced with chimeric VLP. Administration of VLP/ovalbumin conjugate provoked
      high titre ovalbumin-specific antibody in mice, demonstrating the immune
      stimulatory properties of the capsid were conferred to conjugated foreign
      antigen. VLP facilitated delivery of conjugated antigen to dendritic cells,
      eliciting proliferative responses in naive TCR transgenic T helper cells that
      were at least 10-fold greater than ovalbumin antigen delivered alone.

PMID- 17546688
TI  - A new process for the continuous production of succinic acid from glucose at high
      yield, titer, and productivity.
AB  - A novel three stages continuous fermentation process for the bioproduction of
      succinic acid at high concentration, productivity and yield using A.
      succiniciproducens was developed. This process combined an integrated membrane
      bioreactor-electrodialysis system. An energetic characterization of A.
      succiniciproducens during anaerobic cultured in a cell recycle bioreactor was
      done first. The very low value of Y(ATP) obtained suggests that an ATP dependent
      mechanism of succinate export is present in A. succiniciproducens. Under the best
      culture conditions, biomass concentration and succinate volumetric productivity
      reach values of 42 g/L and 14.8 g/L.h. These values are respectively 28 and 20
      times higher compared to batch cultures done in our laboratory. To limit end
      products inhibition on growth, a mono-polar electrodialysis pilot was secondly
      coupled to the cell recycle bioreactor. This system allowed to continuously
      remove succinate and acetate from the permeate and recycle an organic acids
      depleted solution in the reactor. The integrated membrane-bioreactor
      electrodialysis process produced a five times concentrated succinate solution (83
      g/L) compared to the cell recycle reactor system, at a high average succinate
      yield of 1.35 mol/mol and a slightly lower volumetric productivity of 10.4 g/L.h.
      The process combined maximal production yield to high productivity and titer and
      could be economically viable for the development of a biological route for
      succinic acid production.

PMID- 17546689
TI  - Pretreatment of eucalyptus wood chips for enzymatic saccharification using
      combined sulfuric acid-free ethanol cooking and ball milling.
AB  - A combined sulfuric acid-free ethanol cooking and pulverization process was
      developed in order to achieve the complete saccharification of the cellulosic
      component of woody biomass, thereby avoiding the problems associated with the use
      of strong acid catalysts. Eucalyptus wood chips were used as a raw material and
      exposed to an ethanol/water/acetic acid mixed solvent in an autoclave. This
      process can cause the fibrillation of wood chips. During the process, the
      production of furfural due to an excessive degradation of polysaccharide
      components was extremely low and delignification was insignificant. Therefore,
      the cooking process is regarded not as a delignification but as an activation of
      the original wood. Subsequently, the activated solid products were pulverized by
      ball-milling in order to improve their enzymatic digestibility. Enzymatic
      hydrolysis experiments demonstrated that the conversion of the cellulosic
      components into glucose attained 100% under optimal conditions. Wide-angle X-ray
      diffractometry and particle size distribution analysis revealed that the scale
      affecting the improvement of enzymatic digestibility ranged from 10 nm to 1
      microm. Field emission scanning electron microscopy depicted that the sulfuric
      acid-free ethanol cooking induced a pore formation by the removal of part of the
      lignin and hemicellulose fractions in the size range from a few of tens
      nanometers to several hundred nanometers.

PMID- 17546690
TI  - Online monitoring of microcarrier based fibroblast cultivations with in situ
      microscopy.
AB  - Animal cell culture is widely used in biotechnology for the production of many
      biological products. In situ microscopes acquire images directly from cell
      suspensions and analyze the images in matters of cell concentration, cell size
      distribution and cell morphology. Their applicability was already proven for
      yeast and suspended mammalian cell cultivations. In this work the in situ
      microscope was utilized to measure the level of colonization of fibroblasts on
      microcarrier surfaces during cultivation. For this study the murine cell line NIH
      3T3 was used in combination with Cytodex 1 microcarriers. Cultivations were
      carried out in a 5 L stirred tank bioreactor equipped with the in situ
      microscope. Images were obtained sequentially with the in situ microscope over
      the whole cultivation time (900 images per sequence, 7.5 h per sequence on
      average). For the microcarrier analysis an image analysis algorithm based on a
      neural network was developed and implemented in the microscope analysis software.

PMID- 17546691
TI  - Inorganic nanoparticles for transfection of mammalian cells and removal of
      viruses from aqueous solutions.
AB  - Owing to their small size, synthetic nanoparticles show unprecedented biophysical
      and biochemical properties which may foster novel advances in life-science
      research. Using flame-spray synthesis technology we have produced non-coated
      aluminum-, calcium-, cerium-, and zirconium-derived inorganic metal oxide
      nanoparticles which not only exhibit high affinity for nucleic acids, but can
      sequester such compounds from aqueous solution. This non-covalent DNA-binding
      capacity was successfully used to transiently transfect a variety of mammalian
      cells including human, reaching transfection efficiencies which compared
      favorably with classic calcium phosphate precipitation (CaP) procedures and
      lipofection. In this straightforward protocol, transfection was enabled by simply
      mixing nanoparticles with DNA in solution prior to addition to the target cell
      population. Transiently transfected cells showed higher production levels of the
      human secreted glycoprotein SEAP compared to isogenic populations transfected
      with established technologies. Inorganic metal oxide nanoparticles also showed a
      high binding capacity to human-pathogenic viruses including adenovirus, adeno
      associated virus and human immunodeficiency virus type 1 and were able to clear
      these pathogens from aqueous solutions. The DNA transfection and viral clearance
      capacities of inorganic metal oxide nanoparticles may provide cost-effective
      biopharmaceutical manufacturing and water treatment in developing countries.

PMID- 17546692
TI  - Diamagnetic levitation changes growth, cell cycle, and gene expression of
      Saccharomyces cerevisiae.
AB  - Inhomogeneous magnetic fields are used in magnetic traps to levitate biological
      specimens by exploiting the natural diamagnetism of virtually all materials.
      Using Saccharomyces cerevisiae, this report investigates whether magnetic field
      (B) induces changes in growth, cell cycle, and gene expression. Comparison to the
      effects of gravity and temperature allowed determination of whether the responses
      are general pathways or stimulus specific. Growth and cell cycle analysis were
      examined in wild-type (WT) yeast and strains with deletions in transcription
      factors Msn4 or Sfp1. Msn4, Sfp1, and Rap1 have been implicated in responses to
      physical forces, but only Msn4 and Sfp1 deletions are viable. Gene expression
      changes were examined in strains bearing GFP-tagged reporters for YIL052C (Sfp1
      dependent), YST-2 (Sfp1/Rap1-dependent), or SSA4 (Msn4-dependent). The cell
      growth and gene expression responses were highly stimulus specific. B increased
      growth only following Msn4 or Sfp1 deletion, associated with decreased G1 and
      G2/M and increased S phase of the cell cycle. In addition, B suppressed
      expression of both YIL052C and YST2. Gravity decreased growth in an Sfp1 but not
      Msn4-dependent manner, in association with decreased G2/M and increased S phase
      of the cell cycle. Additionally, gravity decreased expression of SSA4 and YIL052C
      genes. Temperature increased cell growth in an Msn4- and Sfp1-dependent manner in
      association with increased G1 and G2/M with decreased S phase of the cell cycle.
      In addition, temperature increased YIL052C gene expression. This study shows that
      B has selective effects on cell growth, cell cycle, and gene expression that are
      stimulus specific.

PMID- 17546693
TI  - Acidification of methanol-fed anaerobic granular sludge bioreactors by cobalt
      deprivation: Induction and microbial community dynamics.
AB  - The acidification of mesophilic (30 degrees C) methanol-fed upflow anaerobic
      sludge bed (UASB) reactors induced by cobalt deprivation from the influent was
      investigated by coupling the reactor performance (pH 7.0; organic loading rate
      4.5 g COD . L(-1) . d(-1)) to the microbial ecology of the bioreactor sludge. The
      latter was investigated by specific methanogenic activity (SMA) measurements and
      fluorescence in situ hybridization (FISH) to quantify the abundance of key
      organisms over time. This study hypothesized that under cobalt limiting
      conditions, the SMA on methanol of the sludge gradually decreases, which
      ultimately results in methanol accumulation in the reactor effluent. Once the
      methanol accumulation surpasses a threshold value (about 8.5 mM for the sludge
      investigated), reactor acidification occurs because acetogens outcompete
      methylothrophic methanogens at these elevated methanol concentrations.
      Methanogens present in granular sludge at the time of the acidification do not
      use methanol as the direct substrate and are unable to degrade acetate.
      Methylotrophic/acetoclastic methanogenic activity was found to be lost within 10
      days of reactor operation, coinciding with the disappearance of the
      Methanosarcina population. The loss of SMA on methanol can thus be used as an
      accurate parameter to predict reactor acidification of methanol-fed UASB reactors
      operating under cobalt limiting conditions.

PMID- 17546694
TI  - Protective effect of HLA-B57 on HCV genotype 2 infection in a West African
      population.
AB  - Recovery from Hepatitis C virus (HCV) infection is considered infrequent (<20%)
      in western populations but reaches 50% in West Africa where genotype 2 infection
      is predominant. To investigate the role of cellular immune responses and host
      genetics in this phenomenon, samples from 104 Ghanaian blood donors reactive with
      anti-HCV assays were collected between 2000 and 2005. HCV antibody was confirmed
      by Western blot using genotype 2 recombinant core, E2 and NS3 proteins. Viral
      load and genotype were determined. Samples were stratified into 37 chronic, 35
      recovered infections and 32 false positive. Eighty-one percentage of subjects
      with chronic infection (RNA positive) carried genotype 2 HCV. Cellular immune
      response was investigated in 35 frozen peripheral blood mononuclear cell (PBMC)
      samples suitable for interferon-gamma ELISPOT assay. Twelve out of 24 confirmed
      recovered, 1 out of 5 chronically infected and none of the 6 false-positive
      controls reacted to recombinant proteins. HLA-A, -B and -DR types were determined
      by DNA methodology. HLA-B*57 was significantly more frequent in the group which
      had recovered from HCV infection compared with chronically infected subjects (P =
      0.0053, OR = 8.02). In conclusion, it is hypothesized that the dominance of
      genotype 2 HCV strains may be an important factor explaining the high rate of
      recovery from HCV infections in Ghana via an efficient contribution of HLA-B*57
      which is relatively frequent in the population.

PMID- 17546695
TI  - Molecular diagnosis of beta-thalassemia by multiplex ARMS-PCR: a cost effective
      method for developing countries like Pakistan.

PMID- 17546696
TI  - The impact of maternal serum screening programs for Down syndrome in southeast
      Michigan, 1988-2003.

PMID- 17546697
TI  - Effects of chorionic villus sampling on placental hemodynamic assessed by three
      dimensional power Doppler ultrasonography.

PMID- 17546698
TI  - MLPA as a screening method of aneuploidy and unbalanced chromosomal
      rearrangements in spontaneous miscarriages.
AB  - OBJECTIVE: The present study aims to validate multiplex ligation-dependent probe
      amplification (MLPA) technique with subtelomeric probe mixes as a screening
      method to detect aneuploidy and unbalanced terminal chromosomal rearrangements in
      spontaneous abortions (SAs). METHODS: MLPA with P036B and P070 probe mixes was
      performed on 221 miscarriage DNA samples between the 5th and 24th week of
      gestation. Cytogenetic culture was attempted on 178 miscarriages. Karyotyped
      miscarriages served as controls in this blinded study. Results were confirmed by
      quantitative fluorescent-PCR (QF-PCR). RESULTS: Among the karyotyped
      miscarriages, MLPA was able to detect all the expected aneuploidies, as well as
      an unbalanced product from a reciprocal translocation, and revealed cryptic
      deletions and duplications not visible at the 550-band resolution level. In
      addition, chromosomal anomalies were found in approximately 37% of cases that
      failed to grow or could not be cultivated. As expected, ploidy changes were not
      detected. Copy number variation was found for target sequences of P036B (CYFIP1,
      MRPL41, CAB45) and P070 (DECR2, TNFRSF18) probe mixes. CONCLUSIONS: We propose
      the use of MLPA with subtelomeric probe mixes as a reliable, rapid and economical
      first approach to detect aneuploidy and unbalanced terminal chromosomal
      rearrangements in SAs.

PMID- 17546699
TI  - First-trimester fetal limb biometry in the Chinese population.

PMID- 17546700
TI  - 3D sonographic prenatal diagnosis of lobar holoprosencephaly associated with
      cebocephaly. Assessment and diagnosis with multiplanar reconstruction.

PMID- 17546702
TI  - Evaluation of tumor affinity of mono-[(123)I]iodohypericin and mono
      [(123)I]iodoprotohypericin in a mouse model with a RIF-1 tumor.
AB  - In this study we have compared the tumour-seeking properties of mono
      [(123)I]iodoprotohypericin and mono-[(123)I]iodohypericin in C3H mice with a
      subcutaneous radiation-induced fibrosarcoma-1 tumor. After intravenous injection,
      both tracers were rapidly cleared from all organs and were retained by the
      tumors. There was no significant difference in tumor uptake of the two tracers at
      all studied time points (p > 0.05). To study the plausible mechanism of hypericin
      and mono-iodohypericin uptake in tumor, their plasma binding profile was
      investigated. Both agents show high affinity for low-density lipoproteins and to
      a lesser extent high-density lipoproteins and other heavy proteins. Mono
      [(123)I]iodohypericin appears to be more promising as a tumor diagnostic agent,
      given its faster clearance from all organs.

PMID- 17546703
TI  - A further case with a small supernumerary marker chromosome (sSMC) derived from
      chromosome 1--evidence for high variability in mosaicism in different tissues of
      sSMC carriers.
AB  - A prenatally ascertained case with a de novo small supernumerary marker
      chromosome (sSMC) derived from chromosome 1 is reported. Due to a fetal heart
      defect the parents decided in favour of an induced abortion. Postmortem, a
      molecular cytogenetic study on eleven formalin fixed, paraffin-embedded tissues
      of the fetus was performed, to further characterize the levels of mosaicism of
      the sSMC(1). sSMC presence varied between 13 and 62% within different tissues of
      sSMC carriers. This finding is something common in sSMC carriers and could
      explain why up to the present no clinical correlations for sSMC mosaicism and
      clinical outcome in the corresponding carriers could be established.

PMID- 17546704
TI  - Intrafamilial variability in Fraser syndrome.
AB  - Fraser syndrome (OMIM 219000) is a rare, autosomal recessive disorder
      characterized by cryptophthalmos, cutanaeous syndactyly, malformations of the
      larynx and genitourinary tract, craniofacial dysmorphism, orofacial clefting,
      mental retardation and musculoskeletal anomalies. There is marked interfamilial
      clinical heterogeneity. However, there is strong phenotypic similarity and
      concordance of the degree of severity of the disease within a family. We report a
      family with two cases of Fraser syndrome with marked clinical heterogeneity. One
      case had lethal phenotype with bilateral renal agenesis, while the other had mild
      phenotype with normal kidneys. It has not been reported before and highlights the
      importance of careful screening of pregnancies in families with Fraser syndrome.

PMID- 17546705
TI  - Does offering and performing prenatal screening influence women's attachment to
      their unborn child? A longitudinal randomized controlled trial.
AB  - OBJECTIVE: The question addressed was: Does offering prenatal screening and
      receiving a negative screening outcome influence women's attachment to their
      unborn child? METHODS: Women were offered a nuchal translucency measurement,
      maternal serum screening, or no screening at all in a randomized controlled
      trial. Attachment was measured by a self-developed questionnaire at four points
      in time: before screening was offered, after the offer, after receiving the
      negative screening result (or at comparable points in time) and in the last
      trimester of pregnancy. In the last trimester, the Prenatal Attachment Inventory
      was also filled in. RESULTS: Women who had been offered screening (n = 1031)
      showed more attachment (F(1,1415) = 19.42, p < .001) compared to women who had
      not been offered screening (n = 387). This difference disappeared later in
      pregnancy. At all points in time, negatively screened women (n = 466) had equal
      levels of attachment compared to screening decliners (n = 565). No difference was
      observed between women who received a negative result of the ultrasound screening
      (n = 285) as compared to the blood screening (n = 162). CONCLUSION: Offering
      prenatal screening seems to temporarily increase attachment. However, this
      difference is very small. Attachment is not influenced by whether a blood
      screening or an ultrasound screening is performed.

PMID- 17546706
TI  - Hybridization kinetics on microarray surfaces.
AB  - Kinetic hybridization data are compared to a number of different models. A first
      order Langmuir model provides the best fit to the data.

PMID- 17546707
TI  - New food sources of essential trace elements produced by biotechnology
      facilities.
AB  - Population satiety with trace elements (TE) is a problem that is widely discussed
      in nutrition science. For optimal nutrition, the form of TE eaten in food is very
      important. Organic forms of TE in nutrition are appropriate as human metabolism
      has adapted to these kinds of nutrients during species evolution. This is now
      considered a reason for the beneficial use of biotechnologically produced TE
      sources in human food. Advanced matrixes for TE incorporation are unicellular
      organisms such as yeast, lactobacilli and Spirulina. Addition of inorganic salts
      at certain concentrations into cultivation media enables the mineral ions to
      incorporate into the microbial biomass. As a consequence, the biomass becomes
      enriched with organic forms of incorporated TE, which are presented by their
      complexes with amino acids, proteins and probably lipids and polysaccharides. In
      addition, a new direction of research has made good advances, in which technology
      has been developed for production of organic forms of TE through complex
      formation between transition metals (zinc, copper, manganese, chromium, iron)
      with amino acids and peptides formed during enzymatic hydrolysis of food protein.
      This brief review discusses the results demonstrating the advances in the
      biotechnological production of new TE sources, to obtain food components destined
      for wide prophylaxis of TE deficiency or for dietary treatment of the adverse
      consequences of these deficiencies.

PMID- 17546708
TI  - Impact of chromosomal abnormalities on preimplantation embryo development.
AB  - OBJECTIVES: To evaluate the influence of numerical chromosomal abnormalities on
      preimplantation embryo development. METHODS: This study includes 6936 embryos
      from 1245 women undergoing preimplantation genetic diagnosis (PGD). Indications
      for aneuploidy screening were: recurrent miscarriages, implantation failure,
      severe male factor, advanced maternal age, and mixed causes. Embryo biopsy was
      performed on day 3, and embryos were co-cultured until day 5, when embryo
      transfer was performed. RESULTS: In the aneuploidy screening regimen, normal
      euploid embryos showed significantly higher blastocyst rates (68.2%) compared to
      chromosomally abnormal (42.8%, p < 0.0001) and mosaic (53.7%, p < 0.0001)
      embryos. Among aneuploid embryos for autosomes, higher blastocyst rates were
      observed in trisomies than monosomies, although only statistically significant in
      patients over 36 years of age (50.8 vs 38.9%; p < 0.0001). In contrast, in
      embryos with sex chromosomes aneuploidy, similar blastocyst rates were observed
      between trisomies and monosomy X. CONCLUSION: Embryos with certain types of
      chromosomal abnormalities were negatively selected during preimplantation embryo
      development. Despite this selection, a remarkable percentage of chromosomally
      abnormal embryos can develop normally to blastocyst stage with high probability
      of implantation and pregnancy.

PMID- 17546709
TI  - Atom-transfer radical addition (ATRA) and cyclization (ATRC) reactions catalyzed
      by a mixture of [RuCl(2)Cp*(PPh3)] and Magnesium.
AB  - A new catalytic procedure for atom-transfer radical addition (ATRA) and
      cyclization (ATRC) reactions is described. The combination of the ruthenium(III)
      complex [RuCl(2)Cp*(PPh3)] (Cp*: pentamethylcyclopentadienyl) with magnesium
      allows these reactions to be performed under mild conditions with high
      efficiency. In most cases, the catalyst concentrations required are significantly
      lower than those used in previously reported procedures. It is suggested that
      magnesium acts as a reducing agent that generates and regenerates the
      catalytically active ruthenium(II) species. The precatalyst [RuCl(2)Cp*(PPh3)]
      has been analyzed by X-ray crystallography.

PMID- 17546710
TI  - A dyadic sensitizer for dye solar cells with high energy-transfer efficiency in
      the device.
AB  - A new bichromophoric dyad based on an alkyl-functionalized aminonaphthalimide as
      energy-donor chromophore and [Ru(dcbpy)2(acac)]Cl (dcbpy=4,4'
      dicarboxybipyridine, acac=acetylacetonato) as energy acceptor and sensitizing
      chromophore is synthesized. Efficient quenching of the donor-chromophore emission
      is observed in solution, presumably due to resonant energy transfer. This dyad is
      then used as a sensitizer in a dye solar cell. By comparing the spectral
      properties of transparent dye solar cells sensitized with the dyad and
      [Ru(dcbpy)2(acac)]Cl, it is possible to demonstrate that photons absorbed by the
      donor moiety also contribute significantly to the generation of current. Instead
      of using acceptor luminescence as a probe, enhanced photocurrent generation is
      employed to estimate the energy-transfer efficiency. Fitting theoretical to
      experimental external quantum efficiency functions gives a value for the energy
      transfer efficiency of 85 %. Evaluation of the maximum output power of dye solar
      cells sensitized with the dyad and [Ru(dcbpy)2(acac)]Cl showed, under selective
      illumination at the absorption maximum of the donor chromophore, that the
      introduction of the energy-donor moiety leads to a significant increase in the
      monochromatic maximum output power under blue illumination. This result
      demonstrates the usefulness of energy transfer for the generation of current in
      dye-sensitized solar cells.

PMID- 17546711
TI  - Enhanced growth inhibition of hepatic multicellular tumor spheroids by
      lactosylated poly(ethylene glycol)-siRNA conjugate formulated in PEGylated
      polyplexes.
AB  - PEGylated polyplexes (lac-PEGylated polyplexes) composed of poly(L-lysine) and
      lactosylated poly(ethylene glycol)-small interfering RNA conjugate, which
      inhibits the RecQL1 gene product, were revealed to show an appreciable growth
      inhibition of multicellular HuH-7 spheroids (human hepatocarcinoma cell lines)
      for up to 21 days (IC(50)=6 nM); this system used as an in vitro three
      dimensional (3D) model mimicking the in vivo biology of tumors. The PEGylated
      polyplexes thus prepared had a size of approximately 110 nm with clustered
      lactose moieties on their periphery as targeting ligands for the
      asialoglycoprotein-receptor-expressing HuH-7 cells. In contrast,
      OligofectAMINE/siRNA (cationic lipoplex) was observed to have almost no growth
      inhibitory effect against HuH-7 spheroids, even though the lipoplex showed a
      stronger growth-inhibitory effect than the lac-PEGylated polyplexes on
      conventional monolayer-cultured HuH-7 cells. The FITC-tagged conjugate in the lac
      PEGylated polyplexes showed smooth penetration into the HuH-7 spheroids compared
      with that in the lipoplexes, as observed by confocal fluorescence-scanning
      microscopy. This indicates that the small size of approximately 100 nm and the
      reduced nonspecific interaction due to the nonionic and hydrophilic lactosylated
      PEG layer contributes to the smooth penetration of the PEGylated polyplexes into
      the spheroid interior, eventually facilitating their uptake into the cells
      composing the spheroids. Cellular apoptosis indicating programmed cell death was
      also observed in the HuH-7 spheroids treated with the PEGylated polyplexes,
      revealing that the observed growth inhibition was indeed induced by the RNAi of
      the RecQL1 siRNA. These data suggest that the smart PEGylated polyplexes can
      indeed penetrate into the multiple cell layers of 3D tumor masses in vivo,
      exerting therapeutic effects through the RNAi.

PMID- 17546712
TI  - A probabilistic algorithm for robust interference suppression in
      bioelectromagnetic sensor data.
AB  - Magnetoencephalography (MEG) and electroencephalography (EEG) sensor measurements
      are often contaminated by several interferences such as background activity from
      outside the regions of interest, by biological and non-biological artifacts, and
      by sensor noise. Here, we introduce a probabilistic graphical model and inference
      algorithm based on variational-Bayes expectation-maximization for estimation of
      activity of interest through interference suppression. The algorithm exploits the
      fact that electromagnetic recording data can often be partitioned into baseline
      periods, when only interferences are present, and active time periods, when
      activity of interest is present in addition to interferences. This algorithm is
      found to be robust and efficient and significantly superior to many other
      existing approaches on real and simulated data.

PMID- 17546713
TI  - [Au3Ge45]9- --a binary anion containing a {Ge45} cluster.

PMID- 17546714
TI  - Controlling the bonding of CO on cobalt clusters by coadsorption of H2.

PMID- 17546715
TI  - The generation of aryl anions by double electron transfer to aryl iodides from a
      neutral ground-state organic super-electron donor.

PMID- 17546716
TI  - Catalytic C-F bond activation of hexafluoropropene by rhodium: formation of
      (3,3,3-trifluoropropyl)silanes.

PMID- 17546717
TI  - Double inversion of emulsions by using nanoparticles and a di-chain surfactant.

PMID- 17546718
TI  - Isolation of a cubane-type metal sulfido cluster with a molecular nitrogen
      ligand.

PMID- 17546719
TI  - Synthetic vaccines of tumor-associated glycopeptide antigens by immune-compatible
      thioether linkage to bovine serum albumin.

PMID- 17546720
TI  - A foreign body due to a broken disc punch in the S1 root sleeve.

PMID- 17546721
TI  - [Shift of tasks from physicians to nurses].

PMID- 17546722
TI  - On COURAGE and lessons from the heart.

PMID- 17546724
TI  - Washington update: changing times.

PMID- 17546725
TI  - Biodiversity loss in the ocean: how bad is it?

PMID- 17546726
TI  - Biodiversity loss in the ocean: how bad is it?

PMID- 17546727
TI  - An EZ-diffusion model for response time and accuracy.
AB  - The EZ-diffusion model for two-choice response time tasks takes mean response
      time, the variance of response time, and response accuracy as inputs. The model
      transforms these data via three simple equations to produce unique values for the
      quality of information, response conservativeness, and nondecision time. This
      transformation of observed data in terms of unobserved variables addresses the
      speed-accuracy trade-off and allows an unambiguous quantification of performance
      differences in two-choice response time tasks. The EZ-diffusion model can be
      applied to data-sparse situations to facilitate individual subject analysis. We
      studied the performance of the EZ-diffusion model in terms of parameter recovery
      and robustness against misspecification by using Monte Carlo simulations. The EZ
      model was also applied to a real-world data set.

PMID- 17546728
TI  - Gender differences in object location memory: a meta-analysis.
AB  - The goal of the present study was to quantify the magnitude of gender differences
      in object location memory tasks. A total of 123 effect sizes (d) drawn from 36
      studies were included in a meta-analysis using a hierarchical approach. Object
      identity memory (37 effect sizes) and object location memory (86 effect sizes)
      tasks were analyzed separately. Object identity memory task showed significant
      gender differences that were homogeneous and in favor of women. For the object
      location memory tasks, effect sizes had to be partitioned by age (younger than
      13, between 13 and 18, older than 18), object type (common, uncommon, gender
      neutral, geometric, masculine, feminine), scoring method (accuracy, time,
      distance), and type of measure (recall, recognition) to achieve homogeneity.
      Significant gender differences in favor of females were obtained in all clusters
      above the age of 13, with the exception of feminine, uncommon, and gender-neutral
      objects. Masculine objects and measures of distance produced significant effects
      in favor of males. Implications of these results for future work and for
      theoretical interpretations are discussed.

PMID- 17546729
TI  - Effects of redundant auditory stimuli on reaction time.
AB  - Auditory redundancy gains were assessed in two experiments in which a simple
      reaction time task was used. In each trial, an auditory stimulus was presented to
      the left ear, to the right ear, or simultaneously to both ears. The physical
      difference between auditory stimuli presented to the two ears was systematically
      increased across experiments. No redundancy gains were observed when the stimuli
      were identical pure tones or pure tones of different frequencies (Experiment 1).
      A clear redundancy gain and evidence of coactivation were obtained, however, when
      one stimulus was a pure tone and the other was white noise (Experiment 2).
      Experiment 3 employed a two-alternative forced choice localization task and
      provided evidence that dichotically presented pure tones of different frequencies
      are apparently integrated into a single percept, whereas a pure tone and white
      noise are not fused. The results extend previous findings of redundancy gains and
      coactivation with visual and bimodal stimuli to the auditory modality.
      Furthermore, at least within this modality, the results indicate that redundancy
      gains do not emerge when redundant stimuli are integrated into a single percept.

PMID- 17546730
TI  - Orthogonal cross-task compatibility: abstract spatial coding in dual tasks.
AB  - Spatially orthogonal stimulus and response sets can produce compatibility
      effects. To explore whether such effects cross the border of logically
      independent tasks, we combined a nonspeeded visual task requiring verbal report
      of a stimulus movement (up vs. down) with an auditory reaction time task that
      required a unimanual movement to the left or right. Two experiments demonstrated
      that up stimuli facilitate rightward responses and down stimuli facilitate
      leftward responses, relative to the opposite combinations, thus producing an
      orthogonal cross-task compatibility effect. This effect presumably arises from
      abstract coding with respect to the salient referents of a spatial dimension
      (i.e., up and right), so that coactivation of structurally similar codes leads to
      mutual priming even when the codes refer to different tasks. The present evidence
      for abstract spatial coding extends previously proposed coding principles from
      single-task settings to dual-task settings.

PMID- 17546732
TI  - Homophonic and semantic priming of Japanese Kanji words: a time course study.
AB  - In an examination of the time course of activation of phonological and semantic
      information in processing kanji script, two lexical decision experiments were
      conducted with native readers of Japanese. Kanji targets were preceded at short
      (85-msec) and long (150-msec) intervals by homophonic, semantically related, or
      unrelated primes presented in kanji (Experiment 1) or by hiragana transcriptions
      of the kanji primes (Experiment 2). When primes were in kanji, semantic
      relatedness facilitated kanji target recognition at both intervals but homophonic
      relatedness did not. When primes were in hiragana, kanji target recognition was
      facilitated by homophonic relatedness at both intervals and by semantic
      relatedness only at the longer interval. The absence of homophonic priming of
      kanji targets by kanji primes challenges the universal phonology principle's
      claim that phonology is central to accessing meaning from print. The stimuli used
      in the present study may be downloaded from www.psychonomic.org/archive.

PMID- 17546731
TI  - Iconic gestures prime related concepts: an ERP study.
AB  - To assess priming by iconic gestures, we recorded EEG (at 29 scalp sites) in two
      experiments while adults watched short, soundless videos of spontaneously
      produced, cospeech iconic gestures followed by related or unrelated probe words.
      In Experiment 1, participants classified the relatedness between gestures and
      words. In Experiment 2, they attended to stimuli, and performed an incidental
      recognition memory test on words presented during the EEG recording session.
      Event-related potentials (ERPs) time-locked to the onset of probe words were
      measured, along with response latencies and word recognition rates. Although word
      relatedness did not affect reaction times or recognition rates, contextually
      related probe words elicited less-negative ERPs than did unrelated ones between
      300 and 500 msec after stimulus onset (N400) in both experiments. These findings
      demonstrate sensitivity to semantic relations between iconic gestures and words
      in brain activity engendered during word comprehension.

PMID- 17546733
TI  - Sequential effects in time perception.
AB  - Taylor and Lupker (2001) reported that in a naming task, stimuli were named more
      rapidly when preceded by an easy-to-name stimulus than when preceded by a
      difficult-to-name stimulus (sequential effects). The goal of the present research
      was to investigate whether sequential effects could be explained in terms of time
      perception processes (within the context of Lupker, Brown, and Colombo's [1997]
      time criterion account). Participants were required to name easy and difficult
      stimuli (high-frequency words and nonwords in Experiment 1; words only in
      Experiment 2). Each naming trial was followed by a set of asterisks (*****). The
      participants were required to press a button when they thought the asterisks had
      been presented for exactly 1 sec. Time intervals produced after naming difficult
      stimuli were longer than time intervals produced after naming easy stimuli. That
      is, time perception was affected by the difficulty of word/nonword naming in a
      way that carried over to the next stimulus, supporting the idea that carryover
      effects in time perception may be the source of sequential effects in the naming
      task.

PMID- 17546734
TI  - Orthographic facilitation and phonological inhibition in spoken word recognition:
      a developmental study.
AB  - We investigated the extent to which learning to read and write affects spoken
      word recognition. Previous studies have reported orthographic effects on spoken
      language in skilled readers. However, very few studies have addressed the
      development of these effects as a function of reading expertise. We therefore
      studied orthographic neighborhood (ON) and phonological neighborhood (PN) effects
      in spoken word recognition in beginning and advanced readers and in children with
      developmental dyslexia. We predicted that whereas both beginning and advanced
      readers would show normal PN effects, only advanced readers would show ON
      effects. The results confirmed these predictions. The size of the ON effect on
      spoken word recognition was strongly predicted by written language experience and
      proficiency. In contrast, the size of the PN effect was not affected by reading
      level. Moreover, dyslexic readers showed no orthographic effects on spoken word
      recognition. In sum, these data suggest that orthographic effects on spoken word
      recognition are not artifacts of some uncontrolled spoken language property but
      reflect a genuine influence of orthographic information on spoken word
      recognition.

PMID- 17546735
TI  - Verbal ability modulates the associative neighbors effect.
AB  - The number of associative neighbors (ANs) of a word has been found to modulate
      the associative priming effect (Canas & Bajo, 1994). Pilot studies have shown
      that this influence might be dependent on verbal ability. This possibility was
      examined by comparing the influence of a prime's ANs on the priming effect in
      students with high and low verbal ability, using a lexical decision task.
      Participants with high verbal ability showed a priming effect regardless ofANs.
      In contrast, low-verbal-ability students showed a significant influence of ANs
      upon the priming effect, which was demonstrated in responding to related targets.
      In particular, the lexical decisions to targets that were preceded by primes with
      a large number of ANs were slower. The effects were not modulated by stimulus
      onset asynchrony. The results are discussed in relation to automatic and
      strategic mechanisms of word processing. These findings have important
      implications for studies in the field of word recognition.

PMID- 17546736
TI  - When two heads are not better than one: partner neglect in paired memory tasks.
AB  - People can monitor the accuracy of their own memories and regulate their
      responses accordingly. But can they monitor and make use of another person's
      memory? We document a new phenomenon whereby participants neglect a partner's
      expertise when deciding whether to defer to that partner's memory or to rely on
      their own. In two experiments, participants studied images for more time than,
      less time than, or the same amount of time as a partner, and on subsequent
      recognition tests they were directed to maximize team performance by either
      answering themselves or letting their partner respond. In both experiments,
      individuals failed to use the knowledge that the partner would probably have a
      better memory for certain items. Only when explicitly instructed to estimate
      their accuracy relative to their partner's did participants take advantage of the
      partner's greater expertise.

PMID- 17546737
TI  - Collaboration can improve individual recognition memory: evidence from immediate
      and delayed tests.
AB  - In two experiments, we tested the effects of collaboration on individual
      recognition memory. In Experiment 1, participants studied pictures and words
      either for meaning or for surface properties and made recognition memory
      judgments individually either following group discussion among 3 members
      (collaborative condition) or in the absence of discussion (noncollaborative
      condition). Levels of processing and picture superiority effects were replicated,
      and collaboration significantly increased individual recognition memory.
      Experiment 2 replicated this positive effect and showed that even though memory
      sensitivity declined at longer delays (48 h and 1 week), collaboration continued
      to exert a positive influence. These findings show that (1) consensus is not
      necessary for producing benefits of collaboration on individual recognition, (2)
      collaborative facilitation on individual memory is robust, and (3) collaboration
      enhances individual memory further if conditions predispose individual accuracy
      in the absence of collaboration.

PMID- 17546738
TI  - Learning is impaired by activated intentions.
AB  - Two experiments examined the task interference that sometimes accrues from having
      an intention. In standard prospective memory tasks, latency is often slower to an
      ongoing task performed concurrently with having an intention than it is when no
      intention is given. If the locus of this slowing resulted from different
      attentional allocation policies in the two cases, we predicted that the process
      of learning a word list would be impaired if participants had an intention rather
      than if they did not. Four different event-based prospective memory tasks were
      used in Experiment 1 to demonstrate that worse free recall of a word list
      resulted when studied with a concurrent intention than with a control condition
      that had no intention. In that experiment, linking an intention to a distal
      context that was to occur after learning did not impair free recall. Two time
      based tasks were used in Experiment 2 to demonstrate that possessing a time-based
      prospective memory also hinders learning, unless the intention is linked to a
      future context that is expected to occur after the study session. In the latter
      case, no impairment was obtained.

PMID- 17546739
TI  - Illusions of competence and overestimation of associative memory for identical
      items: evidence from judgments of learning.
AB  - The relation between subjects' predicted and actual memory performance is a
      central issue in the domain of metacognition. In the present study, we examined
      the influence of item similarity and associative strength on judgments of
      learning (JOLs) in a cued recall task. We hypothesized that encoding fluency
      would cause a foresight bias, so that subjects would overestimate recall of
      identical pairs (scale-scale), as compared with strong associates (weight-scale)
      or unrelated pairs (mask-scale). In Experiment 1, JOLs for identical word pairs
      were higher than those for related and unrelated pairs, but later recall of
      identical pairs was lower than recall of related pairs. In Experiment 2, the
      effect of encoding fluency (inferred from self-paced study time) was examined,
      and a similar pattern of results was obtained, with subjects spending the least
      amount of time studying identical pairs. We conclude that overconfidence for
      identical pairs reflects an assessment of item similarity when JOLs are made,
      despite associative strength being a better predictor of later retrieval.

PMID- 17546740
TI  - Psychotropic placebos create resistance to the misinformation effect.
AB  - Can a placebo for a psychotropic drug help participants resist the misinformation
      effect? To answer this question, we gave participants a mixture of baking soda
      and water and told half of them that the mixture was a cognition-enhancing drug
      called R273 and told the other half that it was an inactive version of the drug.
      Shortly thereafter, all participants took part in a three-stage misinformation
      experiment. Compared with participants who were told that they had taken the
      placebo, the participants who were told that they had taken the drug reported
      improved cognitive abilities and were less susceptible to the misinformation
      effect. We provide source-monitoring and mindfulness accounts of our findings.

PMID- 17546741
TI  - Defining task-set reconfiguration: the case of reference point switching.
AB  - Some researchers argue that task switching involves task-set reconfiguration-
      that is, changing the existing task set to perform a different task. Although
      this idea is intriguing, it is often unclear what is reconfigured and which
      processes are involved in reconfiguration. We addressed these issues by defining
      task sets, identifying differences between them, and obtaining evidence that was
      diagnostic of reconfiguration. In two experiments, subjects performed relative
      judgment tasks that involved comparing a target with a reference point that
      repeated or switched across trials. The task was the same on every trial, but the
      task set was not, because a task-set parameter--the reference point--had to be
      changed. Target-reference point distance effects that changed with the reference
      point provided diagnostic evidence that reconfiguration occurred, and this
      reconfiguration led to switch costs. We discuss how our approach can be
      generalized to define reconfiguration more clearly in other task-switching
      situations.

PMID- 17546742
TI  - Electrophysiological evidence of central interference in the control of
      visuospatial attention.
AB  - Visuospatial attention can be deployed to different locations in space without
      movement of the eyes. A large body of human electrophysiological studies reveals
      enhanced sensory-perceptual responses to stimuli that appear at an attended
      location. However, it is not clear that the mechanisms that underlie visuospatial
      attention are under the control of attention mechanisms that limit central
      processing in multiple-task situations. We investigated this question by
      incorporating a visual task that required the deployment of visuospatial
      attention as the second task of psychological refractory period (PRP) dual-task
      paradigms. The N2pc component of the event-related potential was used as an
      electrophysiological index of the moment-by-moment deployment of visuospatial
      attention to monitor when and where observers were attending while they performed
      concurrent central processing known to cause the PRP effect. Electrophysiological
      evidence shows that central processing interfered with the N2pc, suggesting that
      visuospatial attention is under the control of capacity-limited central
      mechanisms.

PMID- 17546743
TI  - Parallel central processing between tasks: evidence from lateralized readiness
      potentials.
AB  - The present dual-task study used lateralized readiness potentials (LRPs) and
      behavioral measures to determine whether response activation for Task 1 and Task
      2 can occur in parallel. We also examined whether task similarity (known as
      dimensional overlap) increases parallel central processing by making it difficult
      to selectively activate one task set. With dimensional overlap, the behavioral
      data replicated previous findings of backward correspondence effects: The Task 1
      response was influenced by its compatibility with the Task 2 response. This
      finding suggests parallel response activation. The LRP data supported this
      conclusion: Task 2 response activation (indexed by the LRP) began before Task 1
      central operations had finished. When there was no dimensional overlap, backward
      correspondence effects could not be measured, but the LRP data confirmed that
      parallel response activation still occurred. We argue that parallel response
      activation does occur, perhaps due to accidental activation of Task 2 mapping
      rules when the intention is to selectively execute Task 1 mapping rules.

PMID- 17546744
TI  - Executive working memory load induces inattentional blindness.
AB  - When attention is engaged in a task, unexpected events in the visual scene may go
      undetected, a phenomenon known as inattentional blindness (IB). At what stage of
      information processing must attention be engaged for IB to occur? Although
      manipulations that tax visuospatial attention can induce IB, the evidence is more
      equivocal for tasks that engage attention at late, central stages of information
      processing. Here, we tested whether IB can be specifically induced by central
      executive processes. An unexpected visual stimulus was presented during the
      retention interval of a working memory task that involved either simply
      maintaining verbal material or rearranging the material into alphabetical order.
      The unexpected stimulus was more likely to be missed during manipulation than
      during simple maintenance of the verbal information. Thus, the engagement of
      executive processes impairs the ability to detect unexpected, task-irrelevant
      stimuli, suggesting that IB can result from central, amodal stages of processing.

PMID- 17546745
TI  - Working memory and the guidance of visual attention: consonance-driven orienting.
AB  - Two experiments investigated the potential role of the content of working memory
      in guiding visual attention. Experiment 1 showed that maintaining a shape in
      working memory resulted in a decisive preference for moving attention to the same
      shape in the background when those shapes were task irrelevant. Experiment 2
      showed a similar preference for words that were semantically related to an item
      held in working memory. We suggest that keeping an item active in working memory
      automatically results in a tendency for attention to be "attracted" to stimuli
      that are related to that item either visually or semantically.

PMID- 17546746
TI  - Visual working memory as the substrate for mental rotation.
AB  - In mental rotation, a mental representation of an object must be rotated while
      the actual object remains visible. Where is this representation stored while it
      is being rotated? To answer this question, observers were asked to perform a
      mental rotation task during the delay interval of a visual working memory task.
      When the working memory task required the storage of object features, substantial
      bidirectional interference was observed between the memory and rotation tasks,
      and the interference increased with the degree of rotation. However, rotation
      dependent interference was not observed when a spatial working memory task was
      used instead of an object working memory task. Thus, the object working memory
      subsystem--not the spatial working memory subsystem--provides the buffer in which
      object representations are stored while they undergo mental rotation. More
      broadly, the nature of the information being stored--not the nature of the
      operations performed on this information--may determine which subsystem stores
      the information.

PMID- 17546747
TI  - Top-down guidance in visual search for facial expressions.
AB  - Using a visual search paradigm, we investigated how a top-down goal modified
      attentional bias for threatening facial expressions. In two experiments,
      participants searched for a facial expression either based on stimulus
      characteristics or a top-down goal. In Experiment 1 participants searched for a
      discrepant facial expression in a homogenous crowd of faces. Consistent with
      previous research, we obtained a shallower response time (RT) slope when the
      target face was angry than when it was happy. In Experiment 2, participants
      searched for a specific type of facial expression (allowing a top-down goal).
      When the display included a target, we found a shallower RT slope for the angry
      than for the happy face search. However, when an angry or happy face was present
      in the display in opposition to the task goal, we obtained equivalent RT slopes,
      suggesting that the mere presence of an angry face in opposition to the task goal
      did not support the well-known angry face superiority effect. Furthermore, RT
      distribution analyses supported the special status of an angry face only when it
      was combined with the top-down goal. On the basis of these results, we suggest
      that a threatening facial expression may guide attention as a high-priority
      stimulus in the absence of a specific goal; however, in the presence of a
      specific goal, the efficiency of facial expression search is dependent on the
      combined influence of a top-down goal and the stimulus characteristics.

PMID- 17546748
TI  - Automatic, stimulus-driven attentional capture by objecthood.
AB  - In three experiments, we investigated whether the mere organization of some
      elements in the visual field by Gestalt factors into a coherent unit (an object),
      with no abrupt onset or any other unique transient, could attract attention
      automatically. Participants viewed a display of nine red and green elements, one
      of which was the target, and had to identify the target's color. On some trials,
      a subset of the elements was grouped by Gestalt factors (collinearity, closure,
      and symmetry) into an object. The object was task-irrelevant and unpredictive of
      the target. Performance on trials with an object present in the display was
      faster than performance on trials with no object for targets in the object area
      (a benefit) but slower for targets in a nonobject area (a cost). These findings
      demonstrate that an object by itself can capture attention automatically in a
      stimulus-driven manner, much as exogenous cues can.

PMID- 17546749
TI  - Perceived object trajectories during occlusion constrain visual statistical
      learning.
AB  - Visual statistical learning of shape sequences was examined in the context of
      occluded object trajectories. In a learning phase, participants viewed a sequence
      of moving shapes whose trajectories and speed profiles elicited either a bouncing
      or a streaming percept: The sequences consisted of a shape moving toward and then
      passing behind an occluder, after which two different shapes emerged from behind
      the occluder. At issue was whether statistical learning linked both object
      transitions equally, or whether the percept of either bouncing or streaming
      constrained the association between pre- and postocclusion objects. In
      familiarity judgments following the learning, participants reliably selected the
      shape pair that conformed to the bouncing or streaming bias that was present
      during the learning phase. A follow-up experiment demonstrated that differential
      eye movements could not account for this finding. These results suggest that
      sequential statistical learning is constrained by the spatiotemporal perceptual
      biases that bind two shapes moving through occlusion, and that this constraint
      thus reduces the computational complexity of visual statistical learning.

PMID- 17546750
TI  - The categorization effect in hedonic contrast: experts differ from novices.
AB  - Test stimuli are rated as less "good" when they follow very good context stimuli
      than when they are presented alone. This diminution in rating is called hedonic
      contrast. Contrast is attenuated if the context and the test stimuli are
      perceived as being in different categories. Because experts use as their basic
      level categories what are the subordinate levels for novices, they will
      categorize when novices do not. Therefore, in the following studies, both experts
      and novices showed hedonic contrast when attractive context orchids preceded more
      neutral test orchids. However, only the novices showed hedonic contrast when
      attractive context irises preceded the test orchids. Novices viewed the irises
      and the orchids as "flowers" and therefore members of the same category,
      resulting in contrast. Experts, however, viewed the irises and the orchids as
      being in different categories; therefore, hedonic contrast did not occur.

PMID- 17546751
TI  - Letter regarding "What is not part of the child abduction news story?".

PMID- 17546752
TI  - Blues pitches institute. Some question insurer-paid efficacy research.

PMID- 17546753
TI  - AHA presents reform agenda. 'Work-in-progress' focuses on coverage, access, cost.

PMID- 17546754
TI  - AMA abstains from IHI crusade. No direct comment on why doc group not involved.

PMID- 17546755
TI  - Sedation for MRI.

PMID- 17546756
TI  - Tackling tobacco: one doctor, one issue, two fronts.

PMID- 17546757
TI  - Not convinced new system is better.

PMID- 17546758
TI  - Re: health, wealth and the pursuit of happiness, March 2007;1 27(2): 61-2.

PMID- 17546759
TI  - Re: cow 2.0 (millennium edition), cutting edge, March 2007; 127(2): 53.

PMID- 17546760
TI  - [Current practice in Fabry disease: a comprehensive multidisciplinary approach].

PMID- 17546761
TI  - [X chromosome].
AB  - X and Y chromosomes hove evolved from a common proto-chromosome, 300 million
      years ago. They shore 29 genes, scottered in two homologous regions (PAR1 and
      PAR2). Ten per cent of humon genetic diseases result from mutations of X-linked
      genes. Disorders with mental handicap, muscle involvement or infertility ore
      overrepresented. X chromosome inactivation is a complex epigenetic process. This
      mechanism keeps a single transcriptionally active chromosome per cell. At
      fecondotion, in XX embryo, the active X is always the maternal one, with the
      paternal X is kept inactive. At the time of implantation of a XX egg,
      inactivation is erased and reinstalled at random in the embryo, except in the
      germinal cell line, where both X remain inactive, and in placenta, where only the
      maternal X is expressed. Skewed inactivation of a X in a woman may indicate the
      presence of a mutated gene on the inactive X. Contrasting with outosomal
      disorders, the difference between recessivity and dominance is often relative, as
      heterozygous women con disclose a phenotype comparable to affected males, as a
      result of random X inactivation.

PMID- 17546762
TI  - [Genetics of Fabry disease: diagnostic and therapeutic implications].
AB  - Fabry disease (FD, OMIM 301500) is an X-linked inborn error of metabolism due to
      mutations in the gene encoding a-galactosidase A, a lysosomal enzyme. FD is an X
      linked disease and affected males are more severely affected than females. In
      Fabry disease, the penetrance and the severity index of the phenotype are high in
      males, while expressivity and severity index appears highly variable and often
      "intermediate" in heterozygous females. Classic definitions of X-linked recessive
      and dominant inheritance neither reflect the variable expressivity, nor take into
      account the multiple mechanisms that can lead to disease expression in
      heterozygous females. The use of the terms X-linked recessive and dominant should
      probably be abandoned, and Fabry disease simply described as following 'X-linked'
      inheritance. Due to random X-chromosomal inactivation, enzymatic detection of
      carriers is often inconclusive. Molecular testing of females at-risk to be
      carriers is therefore mandatory for accurate genetic counselling. The GLA gene
      has been cloned and more than 300 mutations have been identified. Most of them
      are private and have been identified in only one family

PMID- 17546763
TI  - [Announcing the diagnosis of a genetic disease and psychological care of the
      patient and family].
AB  - Announcing a diagnostic of genetic disease to a child is for parents such a pain,
      also brutal and destructive. Even if the physician chooses the best moment, the
      right words, it's a sign of a rupture, a real disaster combined with physical
      feeling of bascule and temporo-spacial confusion. It's a beach in their flesh, a
      lost of identity, a profound norcissic failure. In addition this feature is
      associated with a high feeling of guilt failure with sometimes non logical
      imaginary structures. All those testimonies confirm that the identification of a
      genetic disease is a key in the family history. Announcing a diagnostic almost
      stay in mind as a bad new enduring a period of life when disease was absent or
      undiagnosed. Even if previews complementary investigations were done, the
      revelation still stays a mess. Also the diagnosis could be a relief the beginning
      of a new life with possibility of rebuilding. Regarding genetic diseases, it's
      the whole family that is concerned. The patients will deal with the diseases
      daily sometimes invisible by the circle. After the announcement of the diagnosis,
      the parents will have to structure that life according to the changes that the
      diseases rags in the family Brothers and sisters will have to find their place
      compared to this affetted brother or sister. In the some time as finding answers
      too many questions. The grand parents may feel guilty and wonder how to help the
      parents. The main part to this psychological approach in genetic diseases is to
      give each member of the family his role.

PMID- 17546764
TI  - [Various topics in population genetics].
AB  - Through quite simple mathematic tools, population genetics affords quite simple
      views in biology or medicine as well as the opportunity to enlarge these views
      toward topics like epidemiology and public health. It is quite easy to show that
      every population owns, in its gene pool, a set of deleterious mutations that is
      maintained because it escapes the natural selection. It may also be pointed out
      the efficiency of consanguinity in exacerbating the frequency of genetic
      recessive disease, a newly arisen question in some subpopulotions in Europe. As
      the medicine is more and more efficient, the dysgenic effect of medicine, due to
      the transmission of deleterious mutations, may be estimated and we may conclude
      that it is not as high as some would like to exclaim. The selection has a special
      effect upon genes located on the X chromosome, especially for the one which is
      responsible for the Fabry disease.

PMID- 17546765
TI  - [Fabry disease in childhood].
AB  - Fabry disease is a lysosomal disease caused by the accumulation of
      glycosphingolipids, mainly the globotriaosylceromid (Gb3) in different body
      tissues, mostly the kidney, the heart and the brain. Occuring most frequently
      during childhood, the first signs of the disease (hypohidrosis, ocroporesthesia,
      GI tract signs, and ongiokeratoma) are often unrecognized and the diagnosis is
      delayed. Even though Fabry disease is on x-linked disorder, the carrier females
      can also be symptomatic, and can even present sometimes with a pattern similar to
      that of the males. The availability of enzyme replacement therapy, which can
      potentially prevent the occurrence of renal, cardiac and neurological life
      threatening manifestations, underlines the importance of having an early
      diagnosis. The indications to start enzyme replacement therapy in childhood are
      currently the subject of specialists discussion in France.

PMID- 17546766
TI  - [Functional renal investigation in Fabry disease].
AB  - Progressive decline in kidney function is a cardinal manifestation of Fbry
      disease. Proteinuria is usually the earliest biological marker of renal
      involvement. Renoprotection should associate both effective Enzyme Replocement
      Therapy (ERT) and non-specific anti-proteinuric therapy as recommended for all
      chronic kidney diseases. ERT has demonstrated high efficiency in the early
      clearing of globotriaosylceromide deposits, however the functional protecting
      effect on GFR decrease remains to be validated, especially in patients with CKD
      stage 3 or higher Estimation of GFR should be very cautious using creatinine
      based formulas, leading to measure GFR whenever possible in order to characterize
      the progression of CKD in Fabry patients.

PMID- 17546767
TI  - [Results of enzyme replacement therapy in Fabry disease nephropathy].
AB  - Kidney involvement in Fabry disease is frequent and severe since it leads to
      terminal renal failure in the fifth decode. Enzyme replacement therapy was
      evaluated on kidney function in two phase III trials, each performed with one of
      the two enzymes available (agalsidase beta and agalsidase alpha). A phase IV
      trial was also conducted with agalsidase beta. Results of those three clinical
      trials were consistent, evidencing stabilization of renal function and clearance
      of the sphingolipid deposits in most of the kidney cells. Enzyme replacement
      therapy should be given early since among patients with kidney failure, it
      appeared to be less efficient.

PMID- 17546768
TI  - [Inherited metabolic cardiomyopathies].
AB  - Hypertrophic cardiomyopathies have an estimated prevalence of 1/500. The analysis
      of the genes coding for the 10 most commonly involved sarcomeric proteins, fails
      to detect a mutation in about one third of cases. In some of these cases,
      cardiomyopathy can be attributed to a genetics storage disease with enlarged
      glycogen vacuolss (PRKAG2 deficiency, Danon disease, Pompe disease) and/or
      lysosomol vacuoles (Donon disease, Pompe disease, Fabry disease). These diseases
      all have in common a short PR interval. PRKAG2 deficiency is due to a dominant
      mutation of the gamma2 subunit of the cardiac AMP kinose. It leads to a storage
      cardiomyopathy which may be associated with sudden death in 10% of cases, due to
      ventricular arrhythmia or auriculoventricular blocks. Danon disease is an X
      linked dominant inherited disease characterized by cardiomyopathy, squeletal
      myopathy and mental retardation. Cardiac transplantation is indicated in both
      affected men and women. In the infantile form of Pompe disease, enzyme
      replacement therapy with olglucosidase alpha shows efficacy on cardiac failure
      with a significant regression of ventricular hypertrophy on ECG, echocardiography
      and radiography

PMID- 17546769
TI  - [Perspectives in cardiac cell therapy].
AB  - The objective of cardiac cell therapy is to restore a certain degree of
      functionality of the infarct zones by injecting stem cells. This therapy was
      tested primarily in two clinical fields: chronic heart failure and acute
      myocardial infarction. Clinical trials have showed safety of cardiac cell therapy
      and encouraging efficacy results. Three challenges for on optimal therapeutic
      benefit: prevent cells migration, increase their survival and improve their
      integration within the recipient myocardium. Many perspectives exist in the field
      of regeneration of cardiac tissue.

PMID- 17546770
TI  - [Ischemic stroke in young adults].
AB  - Ischemic strokes are not exceptional in young adults. The causes of cerebral
      ischemia are multiple: arterial (cervical dissection, and to a lesser extent,
      arteriosclerosis, small-vessel occlusion ond vasculopathy) cardiac,
      hematological, genetic etc. Depending on the exhaustivity of the diagnostic work
      up, 30 to 50% of cases have no clear cause. The long-term prognosis for the
      ischemic stroke in the young is better than in the elderly, mortality and
      recurrence rates are low. Many subjects suffer sequeloe that have on important
      impact on quality of life of the patients and their family

PMID- 17546771
TI  - [Neurological aspects of Fabry disease].
AB  - Fabry disease, rare X-linked disorder with deficient activity of alpha
      galactosidase A, leads to a multiple organ failure caused by a progressive
      accumulation of the substrat globotriasocylceramide in cells. Peripheral nerve
      involvement, neuropathic pain and chronic acroparesthesiae, are the most
      frequently reported signs and often revealing the disease. They are secondary to
      the small nerve fibres (fibres 5), that explained the normality of
      electroneuromyography. Cochleovestibular and autonomic nervous system involvement
      appear later in the illness, aseptic meningitis are rare. Cerebrovascular events
      (stroke, transient ischaemic attack) are reported in 25% of patients, increasing
      with age. Affecting essentially the posterior circulation, their etiologies have
      to be clarified. MRI shows numerous silent lesions, increasing with age, mainly
      in small perforant arteries and pulvinar calcifications, due to on increase in
      cerebral perfusion with an impaired cerebral autoregulation, secondary to the
      glycosphingolipid storage in vascular endothelial cells. Enzyme replacement
      therapy could improve cerebral regional blood flow disturbances and painful
      neuropathy

PMID- 17546772
TI  - [Development of an orphan drug to treat a genetic disease: the paradigm of
      agalsidase beta].
AB  - Preclinical and phase I/II studies gave the proof of principle of enzyme
      replacement therapy (ERT) with recombinant alpha-galactosidase A through the
      demonstration of the clearance of the accumulated subtrate from plasma and
      tissues. In a multicenter, randomized, placebo-controlled, double-blind phase Ill
      study, the biological efficacy of recombinant alpha-galactosidose A (agalsidase
      beta 1 mg/kg/714 days) was demonstrated on the basis of complete clearance of
      accumulated globotriaosylceramide from the endothelia of the kidney, heart and
      skin. The phase III extension study data gives additional results: kidney
      function appears to be stabilized after 54 to 60 months of treatment with
      agolsidase beta in most patients. Intent-to-treat analysis of a double-blind,
      randomized, placebo-controlled, phase IV study, showed that, adjusted for on
      imbalance in baseline proteinuria, agalsidase beta significantly reduces by 53%
      the risk of a first clinical event (renal, cardiac and cerebrovascular), compared
      with placebo. Clinical benefits of ERT depend on patients' clinical status at
      baseline, therefore prompting for onset of ERT before irreversible damage occur
      and underlying the need to stratify patients' populations to better understand
      the outcome of ERT.

PMID- 17546773
TI  - [Laboratory diagnosis of Fabry disease: historical perspectives and recent
      breakthroughs].
AB  - Due to its high sensitivity and specificity, determination of the c-galactosidase
      A activity in leukocytes is the gold standard to confirm the diagnosis of Fabry
      disease in hemizygous moles. In contrast, heterozygous females cannot be
      dependably diagnosed by this method and genotyping should always be carried out.
      Two recent breakthroughs have contributed to the rise of screening programs for
      Fabry disease: first, the use of filter papers to collect blood or urine spots
      from individuals in at-risk populations for Fabry disease, second, the
      development of moss spectrometry Substrate accumulation and enzyme activity can
      be measured on urine and blood samples, respectively Moss spectrometry allows the
      qualitative and quantitative determination of the accumulation of the undegraded
      substrate (globotriaosylceromide) in urine, but also the measurement of enzyme
      activities in blood samples for the simultaneous diagnosis of several inborn
      errors of metabolism, among which lysosomal storage diseases and in particular
      Fabry disease.

PMID- 17546774
TI  - [A new imaging technique as a diagnostic tool: mass spectrometry].
AB  - Moss spectrometry proceeds from the generation of gas-phase ions from the
      molecules present in a sample. Recent ionisation methods make use of a focalized
      energy transfer onto a surface, allowing the localized analysis of a solid
      sample. The signals recorded are all the more intense as the corresponding
      molecules are more abundant. The point-by-point recording of mass spectra thus
      enables to generate ion images inasmuch as the translation of ionic intensity
      variations in a colour code creates the visible contrast. By applying mass
      spectrometry imaging to thin tissue slices originating, for example, from
      biopsies, it is possible to detect and locate simultaneously on the tissue
      surface a variety of biomolecules such as lipids, metabolites, drugs or proteins.
      This method can either play a role of support to the clinical diagnostic or
      emerge as a new tool in metabolomic and proteomic studies. The particular case of
      the Fabry disease is presented here in order to illustrate the present
      capabilities of this novel chemical imaging approach.

PMID- 17546775
TI  - [Lysosomal storage diseases: functional classification and treatment principles].
AB  - Until recently, lysosomes were only considered as the place of macromolecules
      degradation. To date, these organelles are considered as playing a key role in
      cellular homeostasis. The knowledge of their complex role allows a better
      understanding of the physiopathology of the diseases resulting from their
      dysfunction. Biosynthesis of lysosomal enzymes and routes for macromolecules
      influx within lysosomes are briefly described and a functional classification of
      lysosomal diseases, which allows a comprehensive approach of treatment rationale,
      is proposed. Except cystinosis which is a lysosomal membrane transport disorder
      the majority of current treatments aim at treating enzymatic defects. Normal
      enzyme can be brought by hoematopoietic cell transplant (or other cell therapies)
      or by infusions of human recombinant enzyme. The normal enzyme can be also
      produced in situ by bringing the normal gene: it is the objective of gene therapy
      The other therapeutic approaches aim at decreasing the quantity of non degraded
      substrate reaching the lysosomes by limiting its biosynthesis or thanks to small
      pharmacologic molecules, at increasing the residual enzyme activity by
      stabilizing the protein (chaperones) or by improving read through possibilities
      of some stop codons in special contexts. The better knowledge of secondary
      phenomena set by the cell in order to try to restore homeostasis which are
      sometimes more deleterious than the storage itself should allow to develop
      complementary treatments. The rationale of these different therapeutic approaches
      and their limits are described in this paper

PMID- 17546776
TI  - [Overview of enzyme replacement therapy in mucopolysaccharidosis].
AB  - Mucopolysaccharidosis are rare, multisystemic and progressive diseases with an
      extremely various clinical spectrum. For the type I, II and VI
      mucopolysaccharidosis, enzyme replacement therapy is available. In these three
      diseases, enzyme replacement therapy induces a reduction in urinary
      glycosaminoglycanes excretion and on improvement in functional tests, 6 minutes
      walk test, pulmonary function test and range of motion.

PMID- 17546777
TI  - [Clinical development of acid alpha-glucosidase for the treatment of Pompe
      disease].
AB  - Alglucosidose alpha has been developed for the treatment of Pompe disease, a
      rare, progressive, and often fatal muscular disease caused by deficient activity
      of the lysosomal enzyme alphaglucosidase. Clinical data from the clinical trials
      show that the enzyme replacement therapy significantly prolongs survival in
      infants, clears glycogen from cardiac muscle and improves cardiac and skeletal
      muscle function. Skeletal muscle response is variable, the best results are noted
      in patients treated early, prior to severe skeletal muscle damage. However there
      are patients who have not a good response despite early treatment. More distance
      is needed to establish the possible role of different other factors in
      determining outcome and the extent of long-term benefit. Trials of enzyme
      replacement therapy in late onset Pompe disease are underway The availability of
      this therapeutic option makes early identification of this condition even more
      critical.

PMID- 17546778
TI  - Obtaining a throat culture.

PMID- 17546779
TI  - New outlook for age-related macular degeneration.

PMID- 17546780
TI  - Does my patient have ulcerative colitis or Crohn's disease?

PMID- 17546781
TI  - Managing pain in a patient who's drug-dependent.

PMID- 17546782
TI  - Blind faith.

PMID- 17546783
TI  - Give event reports their due respect.

PMID- 17546784
TI  - What you need to know about sepsis.

PMID- 17546785
TI  - Cardiac resynchronization therapy.

PMID- 17546786
TI  - Can a bloodless surgery program work in the trauma setting?

PMID- 17546787
TI  - Fighting the triple threat of lower extremity ulcers.

PMID- 17546788
TI  - HPV vaccine: new treatment for an old disease.

PMID- 17546789
TI  - Battling obesity: small steps, big rewards.

PMID- 17546790
TI  - Prevent dangerous hemodialysis catheter disconnections.

PMID- 17546791
TI  - New standards for improving peripheral i.v. catheter securement.

PMID- 17546792
TI  - Combination drugs...

PMID- 17546793
TI  - Suspected cervical spine injury.

PMID- 17546794
TI  - Analysis of recent papers in hypertension.

PMID- 17546795
TI  - Tibotec and Aspen collaborate on Prezista.

PMID- 17546796
TI  - Low incidence of entecavir resistance in nucleoside-naive chronic hepatitis B
      patients.

PMID- 17546797
TI  - Reply to Wood WG. Questionable results--who directs the EQAS organisers?

PMID- 17546798
TI  - Reply to Wood WG. Questionable results--who directs the EQAS organisers?

PMID- 17546799
TI  - Reply to Wood WG. Questionable results--who directs the EQAS organisers?

PMID- 17546800
TI  - Reply to Wood WG. Questionable results--who directs the EQAS organisers?

PMID- 17546801
TI  - Reply to Wood WG. Questionable results--who directs the EQAS organisers? A
      comment from the point of view of the ECAT Foundation.

PMID- 17546802
TI  - Medicare Part D: successes and continuing challenges. Impact of Medicare Part D
      on Massachusetts health programs and beneficiaries.
AB  - On January 1, 2006, the Centers for Medicare and Medicaid Services (CMS)
      implemented the Medicare Drug Benefit, or "Medicare Part D." The program offers
      prescription drug coverage for the one million Medicare beneficiaries in
      Massachusetts. Part D affects Massachusetts state health programs and
      beneficiaries in a number of ways. The program: (1) provides prescription drug
      insurance, including catastrophic coverage, through a choice of private
      prescription drug plans (PDPs) or integrated Medicare Advantage (MA-PD) health
      plans; (2) shifts prescription drug coverage for dual-eligible Medicare /
      Medicaid beneficiaries from Medicaid to Medicare Part D drug plans; (3) requires
      a maintenance-of-effort, or "clawback" payments from states to CMS designed to
      capture a portion of states' Medicaid savings to help finance the benefit; (4)
      offers additional help for premiums and cost sharing to low income beneficiaries
      through the Low Income Subsidy (LIS); and (5) provides a subsidy to employer
      groups that maintain their own prescription drug coverage for retired
      beneficiaries. This paper summarizes the activities involved in implementing
      Medicare Part D, the impact it has had on Massachusetts health programs, and the
      experiences of beneficiaries and others conducting outreach and enrollment. The
      data are drawn from interviews with officials and documents provided by state
      health programs, CMS and the Social Security Administration, and representatives
      of provider and advocacy groups involved in the enrollment and ongoing support of
      Medicare beneficiaries.

PMID- 17546803
TI  - Drugs: just a click away. Online pharmacies can make dangerous drugs easy to get,
      but also can promote better health care. Should we regulate them?

PMID- 17546804
TI  - Women aren't "small men": women's health issues are different than men's and need
      to be addressed specifically.

PMID- 17546805
TI  - Medical self-defense, prohibited experimental therapies, and payment for organs.

PMID- 17546806
TI  - [Multi-resistant tuberculosis in France].

PMID- 17546807
TI  - [Weaning from mechanical ventilation: as from now, a standardized technique?].

PMID- 17546808
TI  - [Weaning from ventilation in the child: a plea to be more rigorous].

PMID- 17546809
TI  - [Therapeutic education in the asthmatic patient].

PMID- 17546810
TI  - [Asthma and atopy: when genetics are involved].

PMID- 17546811
TI  - [Helping patients cope with the psychological burden of chronic disease].

PMID- 17546812
TI  - [Depression, anxiety and coping strategies in adult patients with cystic
      fibrosis].
AB  - The considerable progress that has been made in the treatment of cystic fibrosis
      has significantly increased life expectancy. The multi-disciplinary approach is
      now considered to be a priority by centers providing care for adults with cystic
      fibrosis. The aim of this study was to investigate three psychological
      morbidities that are commonly present with this disease: depression, anxiety and
      poor coping mechanisms for stress. Sixteen subjects (aged 19 to 37 years)
      participated in this study and were divided in three groups according to the
      severity of their pulmonary disease. Assessments of depression and anxiety were
      made from two perspectives: 1) the subject's own perception of his/her depressive
      and anxious state; 2) a psychologist's assessment of the patients depressive and
      anxious state. Then, reactions to stress were explored by analyzing "coping"
      strategies employed. Results indicate that patients underestimated the level of
      their depressive and anxious state when compared to the psychologists assessment.
      The majority of them exhibited "coping" strategies based on emotional responses.
      Levels of anxiety and depression did not show any relationship with the severity
      of pulmonary disease suggesting that the major determinant of emotional well
      being lies with the individual's own perception of their state and of the support
      available to them.

PMID- 17546813
TI  - [Contribution of psychomotricity in respiratory rehabilitation programs].
AB  - Pulmonary rehabilitation traditionally benefits COPD patients through physical
      training, optimization of medical treatment, education and nutritional advice. In
      this paper we introduce psychomotricity which provides these with a more global
      approach to pulmonary rehabilitation. This approach takles postural tone,
      mobility, anxiety and self-confidence in order to improuve control of breathing
      and perception of breathlessness. Consequently handicap is reduced and its
      adverse effects are curbed. Psychomotricity, through corporeal techniques and
      relaxation, complements the other components of pulmonary rehabilitation. We
      report on our experience with ninety patients. All the assessments were carried
      out before and after the program. This study showed significant improvement in
      many outcomes including psychomotricity assessments, quality-of-life
      questionnaire scores and visual analogue scales. Psychomotricity, when
      incorporated into a multi-disciplinary rehabilitation program, appears to help
      patients regain self-confidence and use their capacities in a better way. This
      technique gives patients better control over their handicap and allows them to
      face the future with more dignity.

PMID- 17546814
TI  - [Multi-parameter indices of weaning from mechanical ventilation in children].
AB  - Simple clinical markers have poor sensitivity; specificity and predictive value
      in both infants and adults when predicting the success of weaning from mechanical
      ventilation. Recently, multi-parametric indices, such as the CROP (Compliance
      Respiratory Rate-Oxygenation-Pressure) and the RSB (Rapid-Shallow-Breathing) have
      been used in adults and subsequently in children. The aim of this study was to
      test the value of the pediatric CROP and RSB (CROPp, RSBp) and the accuracy of a
      simplified pediatric CROP (CROPpS) that does not require an arterial blood gas
      sample. MATERIALS AND METHODS: This prospective study was conducted in a
      pediatric ICU which does not admit neonates. All infants were intubated and
      ventilated at the time of entry. Spontaneous tidal volume and maximal negative
      inspiratory pressure, that are required to assess and calculate the indices, were
      measured using a Fleish pneumotachograph and a unidirectional valve. The other
      parameters were recorded or calculated. A maximum 4 hour-duration trial of
      spontaneous ventilation was then performed. Weaning failure was defined as the
      requirement of re-ventilation within 48 hours of extubation. The discriminant
      power of CROPp and RSBp was determined by calculating the area under the receiver
      operating characteristic (ROC) curve. The best cut-off value of the CROPpS was
      determined by chi2 optimisation. RESULTS: 39 children (20 males) were included in
      the trial. They had a median age of 3.2 years and a median duration of mechanical
      ventilation of 1.3 days. 89.7% of children were successfully weaned of mechanical
      ventilation. Sensitivity of CROP, and RSB, was 97% and 94%, specificity was 0%
      and 0%, positive predictive value was 89% and 89%, and negative predictive value
      was 0% and 0% respectively; the area under the ROC curve was 0.57 and 0.74. The
      CROP,S was found to be as accurate as the CROP, index using the same cut-off
      value. Comparison of the 2 groups (success, failure) revealed a significant
      difference in duration of ventilation (longer in the failure group). CONCLUSION:
      Even though they correctly classified 87% and 85% of patients respectively, the
      CROPp and RSBp are not good predictors of weaning from mechanical ventilation as
      the area under the ROC curve is less than 0.80. Other indices need to be
      evaluated.

PMID- 17546815
TI  - [Epidemiological study on the Genetics and Environment of Asthma, bronchial
      hyperresponsiveness and atopy (EGEA) - First results of a multi-disciplinary
      study].
AB  - The French co-operative epidemiological study EGEA realised in 1991/95 combines a
      case control study and a study of the families of asthmatic cases. A synthesis of
      the results already obtained is presented. Smoking was related to IgE, even in
      asthmatics and was clearly related to the clinical severity of asthma, an aspect
      insufficiently taken into account. The relationships of occupational exposures to
      asthma have been assessed using a job exposure matrix. Segregation analyses on
      IgE have shown, after correction for the mode of ascertainment, the existence of
      a dominant major gene and familial residual correlation. A systematic genome
      screen realised in families with 2 asthmatic siblings showed linkage of various
      regions in the genome implicated to asthma or related phenotypes (1p, 11p, 11q,
      12q, 13q, 17q, 19q), coherent with genome screens realised in other studies.
      Regarding candidate genes, no association was evidenced between asthma and the
      AF508 mutation of the cystic fibrosis gene. The analysis is still in progress by
      studies on the heterogeneity of asthma with refined genetic studies and by
      searching to integrate results regarding environmental and genetic factors and
      studying their interactions.

PMID- 17546816
TI  - [Education of the adult asthmatic].
AB  - This article aims to examine educational strategies in the context of the overall
      management of the asthmatic patient. The objectives are analysed from the
      viewpoints of the both the patient and the health care professionnal. The
      complexity of the manifestations of asthma and the variability of perception of
      symptoms require a personalised approach to education. The asthmatic patients, co
      operation with their therapeutic management, in particular in matters of
      compliance, reveals problems common to other chronic conditions. If an agreement
      can be reached during an exchange of beliefs and points of view, this will lead
      to the most appropriate choice of therapy. The evaluation of educational
      strategies has been the subject of many publications and sequential studies must
      be distinguished from randomised controlled trials. Sequential studies of
      educational strategies generally include severe asthmatics, previously under
      treated. The improvement in measured parameters of morbidity is often striking
      but it is difficult to separate the true effect of education from that of
      improved total management, particularly the introduction of preventative
      treatment. Randomised trials with an "uneducated" control group give more
      conflicting results. A particular emphasis may be placed on action plans based on
      monitoring of peak flow and/or symptoms. Finally the inclusion of educational
      strategies in the training programmes of health care professionnals is now well
      established and its impact should be evaluated.

PMID- 17546818
TI  - [Recommendations for nebulizer therapy].

PMID- 17546819
TI  - [Inhalation therapy in asthma].

PMID- 17546820
TI  - [Skeletal muscle metastases from non small cell lung].
AB  - We report a case of metastatic spread to skeletal muscle in a patient with an
      inoperable NSCLC complaining of a painful swelling of the right thigh. The
      treatment included muscle resection, radiotherapy to the thigh and chemotherapy,
      and resulted in complete pain relief There was no local recurrence, but the
      patient developed multiple systemic metastases and died 11 months after the
      muscle resection. Skeletal muscles metastases from lung cancer are rare and
      although indicative of a poor prognosis, local aggressive treatment may be
      worthwhile.

PMID- 17546821
TI  - [Pleural trichomoniasis due to trichomonas tenax].
AB  - Thoracic infections due to Trichomonas species often go unrecognised as they are
      seldom described in the literature. We describe a case that, to our knowledge, is
      the first reported case of empyema caused by this organism. A 59 year old man
      with metastatic adenocarcinoma of the lung developed a right pyopneumothorax
      following treatment with corticosteroids and radiotherapy. The pleural fluid was
      purulent and fetid, and contained large numbers of Trichomonas tenax amongst a
      mixed bacterial flora. Pleural drainage and antibiotic therapy with
      metronidazole, ciprofloxacin and gentalline were instituted immediately, but the
      patient died 4 days later. Trichomonas tenax is part of the normal oral floral
      and may on occasions colonize the airways. It can thus become involved during
      aspiration pneumonia or cause pleural infection following the rupture of a
      pulmonary abscess. Such infection tends to be associated with concurrent
      respiratory pathology or with immunodepression. The significance Trichomonas
      tenax when found in the airways is unclear and their pathogenic role is
      discussed.

PMID- 17546822
TI  - [Sarcoidosis and renal insufficiency].
AB  - Renal complications of sarcoidosis are rare but they may lead to renal failure.
      The two most common mechanisms are interstitial nephritis and acute
      hypercalcaemic renal failure. We report the case of a woman who presented both of
      these complications.

PMID- 17546823
TI  - [Sarcoidosis and pulmonary dust exposure, a plausible pathogenic link].

PMID- 17546824
TI  - [Bronchial carcinoma: an at-risk group who are often not offered the pneumococcal
      vaccine].

PMID- 17546825
TI  - [Asthma in Africa].

PMID- 17546826
TI  - [Consensus critical care conference: weaning from mechanical ventilation. The
      French Language Society of Pneumology (in association with the SPLF)].

PMID- 17546827
TI  - [National Agency for Health Accreditation and Evaluation good practice
      recommendations: educating the asthmatic patient].

PMID- 17546828
TI  - Screening for urologic malignancies in primary care: pros, cons, and
      recommendations.
AB  - Interest in screening for urologic cancers has grown in recent years. This
      article considers the pros and cons of screening for four epidemiologically
      compelling urologic cancers: prostate, bladder, kidney, and testicular.
      Unfortunately, many of the urologic cancers do not meet the criteria for a
      successful cancer screening program-namely, high prevalence, availability of a
      sensitive and specific screening test, ability to detect clinically important
      cancers at an early stage, and cost-effectiveness. While age-based screening for
      prostate cancer should be offered to the general population after discussion of
      its benefits and risks, for the other three urologic malignancies the current
      consensus points more toward selective screening based on specific patient risk
      factors.

PMID- 17546829
TI  - Benign prostatic hyperplasia: when to 'watch and wait,' when and how to treat.
AB  - Benign prostatic hyperplasia (BPH) is a clinical diagnosis. While BPH is a common
      cause of lower urinary tract symptoms (LUTS) in men, LUTS can signify a number of
      other disease states. For this reason, the patient evaluation, which includes a
      digital rectal examination, and careful differential diagnosis are crucial in men
      with LUTS. Many men with BPH are asymptomatic, and many others are not bothered
      by their symptoms; watchful waiting is appropriate management for these patients.
      When symptoms affect quality of life, pharmacologic therapy should be an option;
      choices include an alphablocker, a 5 alpha-reductase inhibitor, or, for men with
      larger prostates, a combination of the two. Surgical intervention is indicated
      when BPH leads to other medical complications, including urinary retention and
      renal insufficiency.

PMID- 17546830
TI  - Overactive bladder: recognition requires vigilance for symptoms.
AB  - Overactive bladder (OAB) is a prevalent condition in both men and women that
      imposes significant burdens on the patient and his or her quality of life.
      Nevertheless, only a small percentage of patients with OAB receive diagnosis and
      treatment. The identification of OAB is well within the scope of the primary care
      provider, as it is symptom-based and does not generally require specialized
      testing. The treatment of OAB relies on behavioral modification and/or
      pharmacologic options, primarily antimuscarinic therapy. Better identification of
      OAB symptoms in the primary care setting should reduce the number of patients
      suffering from untreated OAB.

PMID- 17546831
TI  - Identifying and treating premature ejaculation: importance of the sexual history.
AB  - Premature ejaculation (PE) is one of the most common sexual dysfunctions in men,
      with prevalence rates ranging from 21% to 31%. Because many physicians do not
      inquire about sexual dysfunction and patients are reluctant to offer it as a
      medical complaint, PE is underreported in clinical practice. A sexual history is
      therefore necessary to uncover the diagnosis. PE can have a significant impact on
      the quality of life of the patient and his sexual partner, and may lead to
      psychological distress and loss of self-esteem. It appears that PE has no single
      etiology, and treatments have been based on both its neurophysiologic and
      behavioral components. Although no therapies are currently approved for PE by the
      US Food and Drug Administration, medications that have shown some success include
      selective serotonin reuptake inhibitors, tricyclic antidepressants,
      phosphodiesterase type 5 inhibitors, and topical anesthetics. Behavioral
      techniques have been the mainstay of PE treatment, and include techniques to
      decrease sensory input.

PMID- 17546832
TI  - Interstitial cystitis/painful bladder syndrome: symptom recognition is key to
      early identification, treatment.
AB  - Once thought to be rare, interstitial cystitis (IC) is now believed to have a
      markedly higher prevalence. This potentially devastating disease is also known as
      painful bladder syndrome (PBS) and can significantly impact quality of life. It
      is diagnosed by its symptoms, as there are no proven pathological findings.
      Unfortunately, the symptoms of IC/PBS overlap those of other common disease
      states such as overactive bladder, endometriosis, urinary tract infection, and
      prostatitis, which complicates the differential diagnosis. Understanding the
      presenting symptoms of urinary frequency, urinary urgency, and pelvic pain in the
      presence of otherwise normal findings can enhance primary care providers' ability
      to appropriately identify the disease. Early identification may allow initiation
      of therapy or referral before the disease becomes refractory to standard
      treatment, which typically includes behavioral therapy and possibly multimodal
      drug therapy.

PMID- 17546833
TI  - The patient barrier to growth of bariatric surgery: another French paradox?
AB  - The bariatric surgery community is complaining about the multiple barriers that
      hamper the growth of procedures that have been found to be the only effective
      treatment for morbid obesity. The French situation demonstrates that the number
      of procedures has stabilized after a period of rapid growth, despite the facts
      that the needs are not satisfied and that there are less important barriers to
      surgery than in most countries. This new "French paradox" is understandable if
      one accepts the reluctance of the public audience and an insufficient level of
      evidence for a systematic referral to bariatric surgery. Less invasive procedures
      should make it possible to re-unify the physicians who deal with obesity, as well
      as the implementation of comparatives and randomized clinical studies.

PMID- 17546834
TI  - Anastomotic leak following antecolic versus retrocolic laparoscopic Roux-en-Y
      gastric bypass for morbid obesity.
AB  - BACKGROUND: Laparoscopic Roux-en-Y gastric bypass (LRYGBP) is the most commonly
      performed operation for the treatment of morbid obesity in the United States.
      Previous reports suggest that postoperative complications may be influenced by
      Roux limb orientation (antecolic versus retrocolic), although this remains
      controversial. The aim of this study was to analyze our experience with
      anastomotic leaks following LRYGBP with an antecolic- versus retrocolic-routed
      Roux limb. METHODS: During the 2-year period of June 2003 to June 2005, 353
      patients underwent a LRYGBP. 135 were antecolic and 218 retrocolic. All cases
      were performed by one of three bariatric surgeons. The decision to perform
      antecolic versus retrocolic LRYGBP was left to the surgeon's preference. The
      primary outcome measure was anastomotic leak. RESULTS: Mean follow-up was 28
      weeks. There were no perioperative deaths. Overall complication rate was 16.9%.
      17 gastrojejunal leaks (4.8%) were identified, consisting of 12 intraoperative
      leaks (3.4%) and 5 postoperative leaks (1.4%). Postoperative gastrojejunal leak
      rate was higher in the antecolic group (P=0.04). CONCLUSION: Mortality and
      complication rates were consistent with reported benchmarks on the efficacy and
      safety of LRYGBP. Our review suggests that anastomotic leak may be more common
      after antecolic than after retrocolic LRYGBP for morbid obesity. A prospective
      randomized study is needed to determine whether antecolically-routed Roux limb is
      an independent predictor for anastomotic leak following LRYGBP.

PMID- 17546835
TI  - Endoscopic balloon dilation of stomal stenosis following gastric bypass.
AB  - BACKGROUND: Roux-en-Y gastric bypass (RYGBP) is a common operation for severely
      obese patients, particularly those with co-morbid disease. Postoperative
      complications include those amenable to endoscopic therapy, specifically those
      involving the gastric stoma. METHODS: 26 patients with prior history of RYGBP for
      morbid obesity presented with symptoms of gastric outlet obstruction. Symptoms
      included accelerated weight loss (n=22), nausea/vomiting (n=26), dehydration
      (n=5), and dysphagia (n=2). Endoscopic dilatation was performed using through-the
      scope dilating balloons (8-15 mm). Following dilatation, a steroid solution was
      injected to prevent re-stenosis. RESULTS: Patients underwent 1-7 dilating
      sessions (mean 2.7/patient) at 2-week intervals. Estimated stoma diameter prior
      to dilation ranged from 1 mm to 8 mm (mean 3.5). Following dilation, diameter of
      the stoma increased to 10 to 15 mm (mean 12.4) at final endoscopy. In patients
      requiring a single dilating session (n=7), predilation stoma size was a mean 5.8
      mm (range 3-8 mm), which increased to a mean of 12.7 mm (range 10-15 mm). In
      patients requiring multiple dilating sessions (n=19), pre-dilation stoma size was
      a mean of 2.7 mm (range 0-4 mm), which increased to a mean of 12.2 mm (range 10
      14 mm). 25 of 26 patients had good long-term response, with follow-up of 6-38
      months (mean 26). No treatment-related complications occurred. All had
      appropriate weight loss as determined at the bariatric clinic following
      endoscopic therapy. CONCLUSIONS: Of the complications following bariatric surgery
      that are amenable to endoscopic therapy, stomal stenosis appears to be relatively
      common. Endoscopic balloon dilation is an effective nonsurgical method for
      treatment of stomal stenosis, with no complications observed in this, the largest
      reported, series.

PMID- 17546836
TI  - Early changes in ghrelin following Roux-en-Y gastric bypass: influence of vagal
      nerve functionality?
AB  - BACKGROUND: Roux-en-Y gastric bypass (RYGBP) effectively produces massive weight
      reduction, improving health in morbidly obese patients. The mechanisms for the
      weight loss, and the fate of the excluded gastric mucosa, are not fully
      clarified. To what extent the appetite-stimulating gastric peptide ghrelin is
      affected remains controversial. METHODS: Circulating concentrations of ghrelin,
      pancreatic polypeptide (PP), pepsinogen I (PGI) and gastrin were examined in 15
      morbidly obese patients (median BMI 45 kg/m2) preoperatively, and on days 1, 2,
      4, 6 and at months 1, 6 and 12 after RYGBP. RESULTS: Ghrelin levels fell on
      postoperative day 1 and increased after 1 month to preoperative levels, and rose
      further at 6 and 12 months. PP concentrations decreased on day 1 and subsequently
      returned to preoperative levels. PGI levels peaked transiently the first days
      after surgery and subsequently declined to lower than preoperative levels.
      Gastrin levels were gradually reduced postoperatively. CONCLUSION: Ghrelin and PP
      fall transiently after surgery, possibly due to vagal dysfunction, and
      ultimately, as weight loss ensues, ghrelin secretion increases to higher than
      preoperative levels. The RYBGP procedure affects the gastric mucosa, as reflected
      by a transient increase in circulating PGI, and subsequently, the mucosa in the
      excluded stomach is at rest, as shown by low levels of PGI and gastrin.

PMID- 17546837
TI  - Abnormal findings on routine upper GI series following laparoscopic Roux-en-Y
      gastric bypass.
AB  - BACKGROUND: The use of postoperative upper GI series (UGIS) after laparoscopic
      Roux-en-Y gastric bypass (LRYGBP) varies among bariatric surgeons. The authors
      describe the findings and impact of UGIS after LRYGBP. METHODS: From July 2003 to
      January 2006, 487 patients undergoing primary LRYGBP at a single academic
      institution had a single-contrast Gastrografin UGIS performed on the first
      postoperative day, without complication. Patient and operative demographics were:
      mean age 43 years, mean BMI 47 kg/m2, female 84%, and laparoscopic 100%. RESULTS:
      Of the 487 patients, the UGIS revealed 14 (2.9%) major and 88 (15.2%) minor
      abnormalities. Among the major UGIS abnormalities, 6 (1.2%) demonstrated a
      gastrojejunal anastomotic (GJA) leak, 8 (1.4%) confirmed complete obstruction at
      the GJA, and 1 (0.2%) disclosed a communication with the bypassed stomach. For
      the minor UGIS abnormalities, 45 (9.2%) displayed significant delay in contrast
      passage through the GJA, 23 (5.0%) had evidence of dilated loops of small and/or
      large bowel, and 6 (1.2%) verified miscellaneous abnormal findings (malrotation,
      lower esophageal dysmotility, jejunal clots). Patients with UGIS abnormalities
      necessitated additional procedures, delayed oral intake and/or longer length of
      stay (LOS). CONCLUSIONS: UGIS on postoperative day 1 is a useful means of
      evaluating postoperative LRYGBP anatomy and influenced postoperative care.

PMID- 17546838
TI  - Does pouch size matter?
AB  - BACKGROUND: Mechanical restriction, malabsorption, and hormonal changes appear to
      play a role in weight loss after Roux-en-Y gastric bypass (RYGBP). This
      investigation chose to investigate one aspect of the restrictive role of gastric
      bypass: the pouch size. Our hypothesis was that a small pouch size with no fundus
      after laparoscopic RYGBP (LRYGBP) would lead to greater loss of excess weight and
      weight loss success. METHODS: Upper gastrointestinal radiological (UGI) studies
      were retrospectively reviewed by three blinded experts (2 bariatric surgeons and
      1 expert radiologist), to determine pouch size and fundus size. The following
      grading system was utilized: Size I - smaller than average pouch, Size II -
      average pouch, Size III larger than average pouch, and Size IV - over 3 times the
      size of an average pouch. Fundus 0 - no fundus appreciated, Fundus I - slight
      amount of fundus barely noted, Fundus II - fundus noted, Fundus III - large
      amount of fundus noted, and Fundus IV - majority of the pouch was fundus.
      Percentage of excess weight loss (%EWL) and successful weight loss (A. >50% EWL,
      B. within 50% of ideal body weight, C. loss of >25% of preoperative weight) were
      calculated. RESULTS: There were 59 patients in this study with 97% follow-up of
      >1 year. No Size IV or Fundus IV were noted. There were no statistically
      significant differences between in %EWL or success for either pouch size or
      fundus size. CONCLUSIONS: While there may be a trend for the mean %EWL to be
      lower with larger pouches and larger amounts of fundus, no significant
      differences were found. Larger pouches and the presence of fundus (within reason)
      still result in a high rate of success after LRYGBP.

PMID- 17546839
TI  - Predictors of outcome after gastric bypass surgery.
AB  - BACKGROUND: Weight loss outcome predictions after gastric bypass (GBP) surgery
      based on individual findings have shown relatively little consistency. The
      present study took a more comprehensive approach, utilizing extensive pre-surgery
      interview and psychological test data both individually and in composite
      predictors. METHODS: Pre-surgery data were obtained for 131 morbidly obese
      patients on a 273-item interview and 5 psychological assessment instruments, and
      weight loss measures (simple weight change and BMI change) were obtained at a
      mean of 12.8 months following surgery. RESULTS: Individual predictor variables
      based on existing research findings showed expected but mostly nonsignificant
      correlations with weight loss. Optimal composite predictor variables were
      constructed for 4 general areas of pre-surgery assessment as represented in the
      literature: physica/medical health, psychological health, interpersonal support,
      and eating disorder. Each composite variable significantly predicted weight loss,
      and together they showed multiple correlations of .50 with simple weight change
      and .54 with simple BMI change. CONCLUSIONS: Sustained weight loss after GBP was
      related to a rather wide range of pre-surgery variables, each of which made a
      small contribution, but composite variables grounded in the general literature
      provided more effective prediction. It is cautioned that continued success after
      > or =2 years could be dependent on yet other variables, with a possible
      contribution from some post-surgery factors.

PMID- 17546840
TI  - Band erosion following gastric banding: how to treat it.
AB  - BACKGROUND: Intragastric band migration is an unusual but major long-term
      complication of gastric banding: its frequency ranges from 0.5-3.8% and always
      requires removal of the band. Different laparoscopic, laparotomic or endoscopic
      methods are currently used for band removal. METHODS: 571 morbidly obese patients
      underwent adjustable gastric banding from February 1998 to July 2006. Band
      erosion occurred in 3 patients (0.52%). In addition, 6 such patients were
      referred to our Department from other hospitals. To remove the migrated band, in
      most patients we used an endoscopic approach with a device designed to cut the
      band: the Gastric Band Cutter (AMI, Agency for Medical Innovation). RESULTS: In 7
      of the 9 patients, we used the gastric band cutter to remove the band
      endoscopically. It was able to cut the band successfully in all cases except one,
      where twisting of the cutting wire required conversion from endoscopy to
      laparoscopy. In another case, the band, after being cut, was locked in the
      gastric wall and required laparotomic removal. In 2 patients, we had to remove
      the band surgically - in one case for port-site infection with subphrenic
      abscess, and in the other case for complete band migration into the jejunum
      associated with acute pancreatitis, cholelithiasis and choledocholithiasis.
      CONCLUSION: The Gastric Band Cutter, when used, was successful in dividing the
      band in all cases except one, although we could not always complete the procedure
      endoscopically. Endoscopic removal seems to be the procedure of choice for band
      erosion, because it allows earlier patient discharge and avoids a surgical
      operation. It is advisable to perform the endoscopic removal in the operating
      theater, because of possible complications of the procedure.

PMID- 17546841
TI  - Prospective study of a two-stage operative concept in the treatment of morbid
      obesity: primary lap-band followed if needed by sleeve gastrectomy with duodenal
      switch.
AB  - BACKGROUND: We investigated the success rate of a two-stage operative concept for
      treatment of morbid obesity: primary laparoscopic adjustable gastric banding
      (LAGB, Lap-Band) for all morbidly obese patients, followed by sleeve gastrectomy
      with biliopancreatic diversion (duodenal switch or DS) in case of failure.
      METHODS: From Dec 1996 to May 2004, 366 consecutive patients (female 78%, mean
      age 41 (17-66) years, BMI 44.3 (35-75) kg/m2 were prospectively evaluated, using
      the two-stage operative concept. The follow-up rate after a mean of 4.1 (1-8.4)
      years was 98%. Primary outcome measure was BAROS score, defined according to
      weight loss, quality of life, reduction in co-morbidities, complications and re
      operations. RESULTS: A very good-to-excellent result was found in 118 patients
      (32%), 141 (39%) had a good results, 76 (21%) a fair result, and 31 (8%) were
      failures. 39 patients needed re-banding due to slippage, 68 a DS, and 11 patients
      had band removal. Early morbidity of the Lap-Band was 3.8%, that of DS 13%, and
      mortality was zero. The excess weight loss at last follow-up of all the patients
      was 44% (40% after Lap-Band/rebanding, and 82% 2 years after DS). CONCLUSION: The
      two-stage concept with primary LAGB, followed by DS in case of failure, leads to
      a good result in 71% of morbidly obese patients. LAGB alone does not appear to be
      an adequate procedure for every morbidly obese patient.

PMID- 17546842
TI  - Systemic inflammation in morbidly obese subjects: response to oral
      supplementation with alpha-linolenic acid.
AB  - BACKGROUND: Morbidly obese patients frequently display asymptomatic chronic
      activation of acute phase response, with potentially adverse metabolic and
      cardiovascular consequences. Nutritional preparations to improve this phenomenon
      have rarely been administered. Aiming to investigate the supplementation of
      flaxseed flour, a source of omega-3 fatty acids, a prospective randomized double
      blind cross-over study was designed. METHODS: Outpatient obese subjects (n=41)
      were clinically and biochemically screened, and results for 24 randomized
      subjects are shown. Age was 40.8 +/- 11.6 years (83.3% females) and body mass
      index (BMI) was 47.1 +/- 7.2 kg/m2. Flaxseed flour (Farinha de Linhaca Dourada
      LinoLive, Cisbra, Brazil) in the amount of 30 g/day (5 g of alpha-linolenic acid 
      omega-3) and an equal mass of placebo (manioc flour) were administered for 2
      weeks each. Variables included general biochemical investigation, white blood
      cell count (WBC), C-reactive protein (CRP), serum amyloid A (SAA) and
      fibronectin. RESULTS: No intolerance was registered. Body weight and general
      biochemical indices remained stable. Initial CRP and SAA were elevated (13.7 +/-
      9.9 and 17.4 +/- 8.0 ). WBC (8100 +/- 2100/mm3) and fibronectin (463.2 +/- 61.3
      mg/dL) were acceptable but in the upper normal range. Corresponding findings
      after supplementation of flaxseed were 10.6 +/- 6.2 mg/L, 14.3 +/- 9.2 mg/L, 7300
      +/- 1800/mm3 and 412.8 +/- 38.6 respectively (P<0.05). No change during the
      control period regarding baseline occurred when placebo was randomized to be
      given first; however, when it followed omega-3 supplementation, CRP and SAA
      recovered, whereas WBC and fibronection remained depressed during those 2 weeks
      (7500 +/- 2100/mm3 and 393.2 +/- 75.8 mg/dL, P<0.05). CONCLUSIONS: 1) Various
      inflammatory markers were elevated in the studied population, although not
      necessarily exceeding the normal range; 2) Significant reduction could be
      demonstrated; 3) Some persistent effects of flaxseed supplement 2 weeks after
      discontinuation were observed.

PMID- 17546843
TI  - Parathyroid hormone and bone marker levels in patients with morbid obesity before
      and after biliopancreatic diversion.
AB  - BACKGROUND: Scopinaro biliopancreatic diversion (BPD) is associated with
      malabsorption of calcium and vitamin D, which manifests as a secondary
      hyperparathyroidism (SHP) and may lead to osteopenia. METHODS: 96 morbidly obese
      patients were studied (age 19-60 years, 23 men and 73 women, with mean initial
      BMI 53) following intervention by Scopinaro BPD. The change in iPTH levels, urine
      DPD, Pyrilinks-D of DPC and serum CTx were studied at 0, 3, 6, 12, 18 and 24
      months after surgery. Postoperatively, they were given supplements of calcium and
      vitamin D3. The control group consisted of 67 non-obese women and 10 men.
      RESULTS: The iPTH levels gradually increased after BPD, with a substantial
      difference compared to presurgery levels at month 6. In spite of the calcium and
      vitamin D supplements, 77% of the patients with presurgery SHP did maintain high
      levels of iPTH after 2 years. The percentage of SHP among the patients with
      normal pre-surgery iPTH was 58%. The basal figures of DPD/cre were significantly
      higher than in the control group, 9.06 (4.6-13.5) nM/mMcre vs 3.9 (2.8-5.6) in
      men and 6.75 (5.4-7.9) vs 7.67 (3.3-11.6) in women, but not CTx, 0.24 (0.02-0.89)
      vs 0.22 (0.07-0.55). After the operation, there was a noticeable increase which
      persisted at 2 years. There was a lack of correlation between the levels of iPTH
      and the bone resorption markers, i.e. the first ones decreased from month 6 in
      men and from month 12 in women, while the levels of iPTH continued to increase.
      CONCLUSION: In obese patients, we found no correlation between iPTH levels and
      BMI. Supplements of calcium and vitamin D did not prevent the appearance of SHP
      following BPD. The patients with high pre-surgery iPTH levels have a higher risk
      of malabsorption of calcium and vitamin D. Following malabsorptive bariatric
      surgery, there is an increase in bone resorption, which results in DPD and CTx
      increase. Those markers do not correlate with iPTH, and this may suggest that
      there is a phenomenon of bone reshaping parallel to the loss of weight.

PMID- 17546844
TI  - Reconstructive procedures after massive weight loss.
AB  - BACKGROUND: Following excess weight loss in many patients, a dermolipectomy of
      the abdomen, arms and thighs becomes necessary. This kind of operation was
      offered to 88 former morbidly obese patients after having lost between 50% and
      75% of their excess weight. METHODS AND RESULTS: Abdomen: Because of a distinct
      pannus, a dermolipectomy was performed in 66 females and 16 males. An average of
      2800+/-1381 g of tissue was removed from the females and 3116+/-2195 g from the
      males. Operative time was 166+/-35 and 177+/-46 minutes for the female and male
      patients, respectively. Minor and major wound healing disorders occurred in 23%
      and 19% of the patients. In two females, a panniculectomy (12.4/13.5 kg) was
      performed after they had reached 150 kg of body weight. Thighs: A medial thigh
      lift was performed in 19 females (excision of varicose veins was included in 9
      patients). In patients receiving a dermolipectomy only, 1212 g of tissue was
      removed in 172+/-81 minutes. Five patients had complications (wound infection,
      lymphatic fistula). With both dermolipectomy and varicectomy, 1358 g of tissue
      were removed in 294+/-80 minutes. Four patients developed a wound infection.
      Arms: 7 female patients had brachioplasty performed, with an average of 410 g of
      tissue removed from both arms over a period of 161+/-64 minutes. In one patient,
      a neurolysis of the ulnar nerve became necessary due to postoperative edema.
      CONCLUSIONS: Dermolipectomy and/or panniculectomy should be offered to bariatric
      patients who have lost massive amounts of weight.

PMID- 17546845
TI  - Dehydroepiandrosterone behavior and lipid profile in non-obese women undergoing
      abdominoplasty.
AB  - BACKGROUND: The aim of this study was to determine any change in
      dehydroepiandrosterone (DHEA) and lipid profile in non-obese women after
      abdominoplasty. METHODS: An auto-controlled clinical trial was carried out. 9
      women aged 35 to 40 years with BMI 22-25 kg/m2 were studied. Basal lipid profile
      and DHEA were performed and repeated 1 month postoperatively. Statistical
      analysis used Wilcoxon signed-ranks test (two-tailed). RESULTS: Weight of
      resected specimen was 606.11 +/- 143.4 grams. No significant changes were
      observed in high-density cholesterol (48.0 +/- 9.6 vs 48.8 +/- 11.0 mg/dl;
      P=0.106) or in triglycerides (119.2 +/- 50.9 vs 148.4 +/- 45.8 mg/dl; P = 0.139).
      Significant increases were obtained in DHEA (3.69 +/- 3.05 vs 11.09 +/- 6.3
      ng/ml; P<0.008), low-density cholesterol (LDL) (87.4 +/- 23.5 vs 108.5 +/- 28.3
      mg/dl; P<0.008 and total cholesterol (155.1 +/- 30.6 vs 186.6 +/- 33.1 mg/dl;
      P<0.008). CONCLUSION: Excision of subcutaneous abdominal fat in studies 1 month
      later increased DHEA, whose role is controversial in visceral fat distribution,
      and increased LDL cholesterol and total cholesterol, both risk markers for
      cardiovascular illness.

PMID- 17546846
TI  - Red blood cell aggregation and deformability among patients qualified for
      bariatric surgery.
AB  - BACKGROUND: The study presents red blood cell (RBC) aggregability and
      deformability among obese patients qualified for bariatric surgery and its
      correlation with plasma lipid concentration. METHODS: We studied 40 morbidly
      obese patients who were qualified for bariatric surgery: mean age was 43.5 +/-
      11.3 years, and mean body mass index (BMI) was 48.9 +/- 7.7 kg/m2. The RBC
      deformability and aggregation parameters: aggregation index (AI), syllectogram
      amplitude (AMP) and aggregation half-time (t1/2) were measured by Laser-assisted
      Optical Rotational Cell Analyser - LORCA. RESULTS: Elongation index of RBC was
      significantly lower in obese patients than in the control group (P<0.001) in 3.16
      60.03 Pa shear stresses. Correlations between elongation index and triglyceride
      levels ranged between 0.42 to 0.44 (P<0.05). AI was significantly higher in the
      obese patients (P<0.001), t1/2 and the AMP were decreased (P<0.001) compared to
      the control group. The RBC aggregation index correlated positively with total
      cholesterol level (r = 0.61, P<0.05), non-HDL cholesterol level (r = 0.54,
      P<0.05) and BMI (r = 0.48, P<0.05). Negative correlation presented t1/2 with
      total cholesterol (r = -0.64, P<0.05), non-HDL cholesterol (r = - 0.51, P<0.05)
      and BMI (r= -0.59, P<0.05). CONCLUSION: Obesity is associated with RBC
      rheological disturbances expressed by a decrease in RBC deformability, increased
      total aggregation extent and the alteration of kinetics of RBC aggregation. These
      results may suggest the necessity of introducing treatment forms to correct
      erythrocyte rheological properties, which may improve the blood-flow condition in
      the microcirculation and prevent postoperative complications after bariatric
      surgery.

PMID- 17546847
TI  - ZFP36: a promising candidate gene for obesity-related metabolic complications
      identified by converging genomics.
AB  - BACKGROUND: Few genes have been associated with the metabolic syndrome (MS),
      although its genetic component is well accepted. The aim of this study was to
      compare the adipose tissue gene expression profiles of obese men with and without
      the MS and to apply an integrative genomic approach to propose new candidate
      genes. METHODS: Affymetrix HG-U133 plus 2 arrays have been used for expression
      profiling of omental adipose tissue of non-diabetic obese men with (n=7) and
      without (n=7) the MS, as defined by the NCEP-ATPIII, that undergo a bariatric
      operation. RESULTS: Omentum expresses a total of 23 055 transcripts. Overall, 489
      genes were differentially expressed between the two groups. A total of 80
      differentially expressed genes were located within a previously identified region
      of linkage. In this subset of genes, zinc finger protein 36 (ZFP36) gene has been
      identified as the most promising genetic target for the MS-based mean fold
      expression differences and on biological plausibility. 2 out of 5 identified
      ZFP36 gene polymorphisms have been genotyped in a cohort of 698 obese subjects.
      The minor allele of these polymorphisms was associated with a lower body weight
      in women (rs251864; P< or =0.01) and glucose level in men (c.1564_1565delTT;
      P<0.05). The haplogenotype was associated with plasma LDL-cholesterol levels in
      men and women (P< or =0.02), and weight in women (P< or =0.05). The haplogenotype
      was also associated with omental adipose tissue ZFP36 mRNA levels (n=83 women;
      P=0.02), and explained 10.1% of its variance. CONCLUSION: These results suggest
      that converging genomics is helpful to prioritize MS-related candidate genes and
      that ZFP36 is a promising candidate gene for obesity-associated metabolic
      complications.

PMID- 17546848
TI  - Gallbladder disease among obese patients in Taiwan.
AB  - BACKGROUND: Obesity is a risk factor for gallbladder disease. The authors analyze
      the prevalence and clinicopathology of gallbladder disease among obese patients
      in Taiwan. METHODS: Prevalence and various clinical factors associated with
      cholelithiasis were studied in 199 patients who were undergoing bariatric surgery
      for obesity. Clinical data (gender, age, BMI and associated diseases), laboratory
      evaluation and immunoglobulin G antibodies against Helicobacter pylori were
      obtained from the patient records. The histopathologic findings of the
      gallbladder were also examined retrospectively. The degree of acute inflammation,
      chronic inflammation, cholesterolosis, cholesterol polyp and gastric metaplasia
      was determined and scored. RESULTS: Of the patients, 91% (n=181) were females and
      9% (n=18) were males, age 34.26 +/- 8.41 years, with mean BMI 35.28 +/- 6.11
      kg/m2. The prevalence of cholelithiasis was 10.1%. Increased diastolic blood
      pressure and HBsAg carrier were the only significant factors associated with
      cholelithiasis. All obese patients in our study presented with variable degrees
      of chronic mononuclear cell infiltration in the gallbladder mucosa.
      Cholesterolosis was present in 100 patients (50.3%), followed by gastric
      metaplasia (27.1%), cholesterol polyp (16.1%) and acute inflammation (9.5%).
      Multivariate analysis showed an association between cholelithiasis and acute and
      chronic inflammation. The predictors of cholesterolosis were BMI, waist
      circumference and high-sensitivity C-reactive protein. The seroprevalence of H.
      pylori was 42.2%. Older age, abnormal liver function tests, calcium and HBsAg
      carrier were significantly different between H. pylori-seropositive and H. pylori
      seronegative obese patients. However, we could rarely find H. pylori within the
      gallbladder mucosa. CONCLUSION: Cholelithiasis in Asian obese patients is
      significantly associated with increased diastolic blood pressure and hepatitis B
      surface antigen carriers. Because chronic liver disease seems to be a risk factor
      for cholelithiasis in both non-obese and obese populations, prophylactic
      cholecystectomy can be considered in obese patients with HBsAg positivity. We did
      not find evidence that H. pylori has a role in the pathogenesis of gallbladder
      disease and gallstone by histologic and serologic examinations. Furthermore,
      mucosal abnormalities of acute and chronic inflammatory cell infiltration are
      common in obese patients, which related to cholelithiasis.

PMID- 17546849
TI  - Psychological distress in morbid obesity in relation to weight history.
AB  - BACKGROUND: Very few data are available on psychological distress in morbidly
      obese subjects in relation to the history of their weight. In subjects with
      childhood obesity, psychological distress might be better than in adult-onset
      obesity, because of progressive adaptation to the social stigma. METHODS:
      Psychological distress was tested in relation to BMI at age 20 years (BMI-20),
      weight history and somatic co-morbidities in 632 treatment-seeking, morbidly
      obese participants from the QUOVADIS cohort (130 men, 502 women; mean age 45.5
      years). The number of dieting attempts/year, BMI increase and cumulative BMI loss
      since age 20 were calculated as weight cycling parameters. The Symptom Check List
      90 (SCL-90), the Psychological General Well-Being (PGWB), the Binge-Eating Scale,
      and the ORWELL-97 questionnaire were used to score psychometry and health-related
      quality of life (HRQL). Complications were quantitatively assessed by a modified
      Charlson's score. RESULTS: BMI-20 was normal in 35% of cases and >35 kg/m2 in
      only 14%. Psychometric scores were not different in relation to BMI-20, when
      corrected for age, with the exception of the General Health scale of PGWB,
      showing a greater distress in subjects with normal BMI-20. In most cases, the
      prevalence of pathological results of questionnaires showed a J-shaped curve,
      with participants with normal BMI-20 or those with Class II-III obesity in early
      adulthood having the highest prevalence of psychological/psychiatric distress and
      poor HRQL. Weight cycling was a risk factor for binge-eating, depression and
      interpersonal sensitivity in SCL-90, whereas somatic co-morbidities adversely
      affected most SCL-90 and all PGWB scales. CONCLUSION: Weight cycling and somatic
      co-morbidities, but not age of onset of obesity, are the main factors negatively
      influencing psychological health in treatment-seeking, morbidly obese subjects.

PMID- 17546850
TI  - Obesity surgery in England: an examination of the health episode statistics 1996
      2005.
AB  - BACKGROUND: The authors examined the uptake of obesity surgery across England.
      METHODS: Data were analyzed from the Hospital Episode Statistics covering all 9
      goverment office regions with a total population of 49.1 million. The data
      analyzed covered 9 years 1996/97 - 2004/05. RESULTS: 1,465 records were
      identified with a primary diagnostic code for obesity and an operation code for
      obesity surgery. The surgery was performed mostly in women (male to female ratio
      of 1:5), who were predominantly mid-aged (average 40.4 years +/- SD 9.00), the
      majority of whom reside in local authority districts ranked within the lowest two
      deprivation quintiles. The availability of obesity surgery varied considerably
      across the 9 different regions of England, although the number of operations
      increased nationally over time. CONCLUSIONS: Access to this intervention is
      highly variable and does not appear to reflect estimated regional differences in
      morbid obesity. This specialist service may benefit from more effective national
      organization, to ensure appropriate capacity and eliminate inequalities in
      service delivery.

PMID- 17546851
TI  - Gastric/intestinal electrical stimulation modulates appetite regulatory peptide
      hormones in the stomach and duodenum in rats.
AB  - BACKGROUND: Gastric/intestinal electrical stimulation (GIES) has been used to
      suppress appetite in the treatment of obesity with promising results. However,
      the mechanisms by which GIES benefits obese patients are not completely
      understood. This study investigated the acute effects of GIES on gastric and
      intestinal tissue levels of peptide hormones related to satiety and appetite in
      rats. METHODS: 32 rats were divided into 4 groups: 1) sham stimulation, 2)
      gastric electrical stimulation (GES) with pulse trains, 3) GES with long pulse,
      and 4) duodenal electrical stimulation (DES) with pulse trains. After 2 hours of
      GIES, the rats were sacrificed immediately, and gastric fundus, duodenum and
      distal colon were harvested and extracted. Hormone levels of ghrelin, obestatin,
      cholecystokinin-8 (CCK-8) and peptide YY (PYY) were measured by radioimmunoassay
      (RIA). RESULTS: 1) The mean gastric fundus ghrelin level was 1789.04+/-362.81
      pg/mg in the sham stimulation and significantly decreased with GES of pulse
      trains (597.85+/-195.33 pg/mg, P=0.012), GES of long pulse (754.6+/-282.6 pg/mg,
      P=0.039) and DES (731.69+/-110.84 pg/mg, P=0.037). 2) The mean duodenal CCK-8
      concentration was 413.27+/-42.14 pg/mg in the sham stimulation and significantly
      increased by DES (762.6+/-98.75 pg/mg, P=0.013) but not in others. 3) Neither
      gastric obestatin nor distal colonic PYY was altered by any of GES or DES.
      CONCLUSIONS: GIES significantly impacts appetite-related peptide hormones in
      gastric and duodenal tissues. Acute GIES-induced manipulation of gut peptide
      hormones related to appetite and satiety is a nonpharmacologic, well-tolerated
      clinical procedure that could substantially contribute to the successful
      treatment and long-term management of obesity.

PMID- 17546852
TI  - Hepatobiliary scintigraphy as a diagnostic modality for gastroparesis of the
      bypassed stomach after gastric bypass for morbid obesity.
AB  - After Roux-en-Y gastric bypass (RYGBP), the excluded gastric remnant represents a
      challenge for the surgeon. Many diseases are reported to take place in that
      remnant, such as cancer, gastritis, and ulcer. On the other hand, diagnosing
      these pathological changes requires invasive intervention. We report the use of a
      noninvasive study to diagnose pathology in the bypassed stomach.

PMID- 17546853
TI  - Laparoscopic transgastric access to the biliary tree after Roux-en-Y gastric
      bypass.
AB  - Gallstone disease, common after Roux-en-Y gastric bypass (RYGBP), may be
      complicated by biliary duct obstruction and gallstone pancreatitis. Although
      endoscopic retrograde cholangiopancreatography plays an important role in
      management of biliary duct obstruction, the altered anatomy of patients who have
      had a RYGBP makes this procedure technically difficult. With the increased number
      of patients undergoing RYGBP for morbid obesity, bariatric surgeons may benefit
      from an alternative laparoscopic technique for accessing the biliary tree. We
      describe a laparoscopic technique of accessing the biliary tree through the
      bypassed stomach.

PMID- 17546854
TI  - Invited commentary. The gastric remnant and duodenum after gastric bypass are
      accessible via combined laparoscopic/endoscopic techniques.

PMID- 17546855
TI  - Laparoscopic solution for early gastric cancer in a morbidly obese patient.
AB  - During preoperative work-up for laparoscopic gastric bypass in a morbidly obese
      female, gastroscopy visualized two small ulcers in the antrum. Biopsies diagnosed
      adenocarcinoma of the diffuse type. Staging was performed, and endoscopic
      ultrasonography showed early gastric cancer. A laparoscopic neartotal gastrectomy
      with D1 resection and perigastric lymph node dissection and full omentectomy in
      combination with a gastric bypass, was peformed. This approach respects the
      oncologic and bariatric principles and gives a combined solution for the patient.

PMID- 17546856
TI  - Vertical gastric resection (sleeve gastrectomy) in a morbidly obese patient with
      past jejunoileal bypass.
AB  - Jejunoileal bypass (JIB) is a purely malabsorptive operation, which has been
      abandoned in the USA and Western Europe due to occasional serious complications.
      We are still seeing past JIB patients who have become obese again over the years,
      but are not suffering side-effects of the previous JIB, and are complaining of
      typical co-morbidities of the obesity. We present a prior JIB patient who
      underwent a sleeve gastrectomy in 2003 for recurrence of morbid obesity. The
      patient has been followed for another 4 years with regular laboratory tests,
      monitoring of weight loss, bone densitometry and possible complications. Selected
      morbidly obese patients who have undergone past JIB, can be safely treated by a
      restrictive procedure, sleeve gastrectomy, to accomplish successful weight loss
      without increasing the risk of possible serious complications.

PMID- 17546857
TI  - New device for introduction of circular stapler.

PMID- 17546858
TI  - An overview of the dental pulp: its functions and responses to injury.
AB  - The dental pulp is a unique tissue and its importance in the long-term prognosis
      of the tooth is often ignored by clinicians. It is unique in that it resides in a
      rigid chamber which provides strong mechanical support and protection from the
      microbial rich oral environment. If this rigid shell loses its structural
      integrity, the pulp is under the threat of the adverse stimuli from the mouth,
      such as caries, cracks, fractures and open restoration margins, all of which
      provide pathways for micro-organisms and their toxins to enter the pulp. The pulp
      initially responds to irritation by becoming inflamed and, if left untreated,
      this will progress to pulp necrosis and infection. The inflammation will also
      spread to the surrounding alveolar bone and cause periapical pathosis. The
      magnitude of pulp-related problems should not be underestimated since their most
      serious consequence is oral sepsis, which can be life threatening, and hence
      correct diagnosis and management are essential. Clinicians must have a thorough
      understanding of the physiological and pathological features of the dental pulp
      as well as the biological consequences of treatment interventions.

PMID- 17546859
TI  - A clinical classification of the status of the pulp and the root canal system.
AB  - Many different classification systems have been advocated for pulp diseases.
      However, most of them are based on histopathological findings rather than
      clinical findings which leads to confusion since there is little correlation
      between them. Most classifications mix clinical and histological terms resulting
      in misleading terminology and diagnoses. This in turn leads to further confusion
      and uncertainty in clinical practice when a rational treatment plan needs to be
      established in order to manage a specific pathological entity. A simple, yet
      practical classification of pulp diseases which uses terminology related to
      clinical findings is proposed. This classification will help clinicians
      understand the progressive nature of the pulp disease processes and direct them
      to the most appropriate and conservative treatment strategy for each condition.
      With a comprehensive knowledge of the pathophysiology of pain and inflammation in
      the pulp tissues, clinicians may accomplish this task with confidence.

PMID- 17546860
TI  - Treatment planning the endodontic case.
AB  - Following a definitive diagnosis of the need for root canal treatment, the
      treatment planning stage should be straightforward if a logical sequence of
      decision-making is followed. Very few contra-indications exist for providing root
      canal treatment, but the planning must include several aspects. Firstly, is root
      canal treatment best for the patient to maintain a functional dentition long
      term? Secondly, who should provide the treatment? Thirdly, what are the
      restorative options that will ensure the best long-term prognosis? The sequencing
      of root canal treatment generally occurs early in a typical treatment plan, and
      prompt restoration after treatment is crucial to long-term survival of the tooth.

PMID- 17546861
TI  - A big role for the very small--understanding the endodontic microbial flora.
AB  - Apical periodontitis, an inflammatory process around the apex of a tooth root, is
      primarily a sequel to microbial infection of the pulp space. The microbial flora
      is composed of a restricted group of the total oral flora, selected by
      environmental pressures of anaerobiosis, nutrition and competition with other
      species and inhabits the root canal as a biofilm of coaggregated communities in
      an extracellular matrix. The untreated infected canal is generally composed of a
      polymicrobial mix with approximately equal proportions of Gram-positive and Gram
      negative species, dominated by obligate anaerobes. The type of microbial flora in
      the root-filled tooth with persistent apical periodontitis has very different
      characteristics. These infections are characterized by one or just a few species,
      predominantly Gram-positive micro-organisms with an equal distribution of
      facultative and obligate anaerobes. Enterococcus faecalis has been a conspicuous
      finding in most studies. Because the primary aetiological problem is infection,
      endodontic treatment is directed at control and elimination of the root canal
      flora by working in a sterile way. Based on current knowledge, the best available
      method for obtaining clean, microbe-free root canals is by instrumentation with
      antimicrobial irrigation reinforced by an intracanal dressing with calcium
      hydroxide.

PMID- 17546862
TI  - The principles of techniques for cleaning root canals.
AB  - Chemomechanical preparation of the root canal includes both mechanical
      instrumentation and antibacterial irrigation, and is principally directed toward
      the elimination of micro-organisms from the root canal system. A variety of
      instruments and techniques have been developed and described for this critical
      stage of root canal treatment. Since their introduction in 1988, nickel-titanium
      (NiTi) rotary instruments have become a mainstay in clinical endodontics because
      of their exceptional ability to shape root canals with potentially fewer
      procedural complications. Safe clinical usage of NiTi instruments requires an
      understanding of basic metallurgy of the alloy including fracture mechanisms and
      their correlation to canal anatomy. This paper reviews the biologic principles of
      preparing root canals with an emphasis on correct use of current rotary NiTi
      instrumentation techniques and systems. The role and properties of contemporary
      root canal irrigants is also discussed.

PMID- 17546863
TI  - The use of calcium hydroxide, antibiotics and biocides as antimicrobial
      medicaments in endodontics.
AB  - Bacteria have been implicated in the pathogenesis and progression of pulp and
      periapical diseases. The primary aim of endodontic treatment is to remove as many
      bacteria as possible from the root canal system and then to create an environment
      in which any remaining organisms cannot survive. This can only be achieved
      through the use of a combination of aseptic treatment techniques, chemomechanical
      preparation of the root canal, antimicrobial irrigating solutions and intracanal
      medicaments. The choice of which intracanal medicament to use is dependent on
      having an accurate diagnosis of the condition being treated, as well as a
      thorough knowledge of the type of organisms likely to be involved and their
      mechanisms of growth and survival. Since the disease is likely to have been
      caused by the presence of bacteria within the root canal, the use of an
      antimicrobial agent is essential. Many medicaments have been used in an attempt
      to achieve the above aims but no single preparation has been found to be
      completely predictable or effective. Commonly used medicaments include calcium
      hydroxide, antibiotics, non-phenolic biocides, phenolic biocides and iodine
      compounds. Each has advantages and disadvantages, and further research is
      required to determine which is best suited for root canal infections.

PMID- 17546864
TI  - Interim and temporary restoration of teeth during endodontic treatment.
AB  - One of the main aims of endodontic treatment is to eliminate micro-organisms from
      within the root canal system. A further aim is to prevent the ingress of any
      further bacteria during and after treatment. These aims are usually achieved by
      various means and stages throughout the treatment process. Endodontic treatment
      is usually performed on teeth that have lost the integrity of the external
      coronal tooth structure which has allowed bacteria to enter the tooth and
      ultimately reach the pulp space. Further opening of the tooth occurs when an
      endodontic access cavity is made to allow treatment to be performed. Hence, there
      will always be a need for interim and temporary restoration of teeth undergoing
      endodontic treatment. Many different materials and techniques have been proposed,
      and these proposals have been based on many research reports. The purposes of
      this article are to review the literature regarding the use of interim and
      temporary restorations, and to provide recommendations regarding such
      restorations for clinicians to follow when providing endodontic treatment.

PMID- 17546865
TI  - The differential diagnosis of toothache from other orofacial pains in clinical
      practice.
AB  - BACKGROUND: Teeth are a common and obvious source of orofacial pain. There is a
      risk that endodontic treatment may be initiated in patients that do not have pulp
      or periapical pathosis. METHODS: A retrospective survey of a sample of patients
      referred for endodontic treatment was analysed to determine the accuracy of the
      diagnosis and to identify non-dental cases. A separate prospective study of
      complex non-dental orofacial pain cases was performed to determine which cases
      had previously received dental treatment. RESULTS: Seventy-seven (88 per cent) of
      88 patients referred for endodontic treatment had been correctly diagnosed with
      solely endodontic problems. Eight (9 per cent) had endodontic plus other
      orofacial pain problems and three (3 per cent) had no endodontic problems but
      other orofacial pain problems. Forty-four (44 per cent) of 100 non-dental
      orofacial pain patients had previously received either extractions or
      endodontics. CONCLUSION: Dentists need to carefully evaluate all toothache
      patients to ensure that the diagnosis is correct prior to the initiation of
      irreversible treatment.

PMID- 17546866
TI  - Management of tooth resorption.
AB  - A correct diagnosis and an understanding of the aetiology and dynamics of the
      processes involved in tooth resorption is critical to effective management. Tooth
      resorptions can be classified as: (1) trauma induced; (2) infection induced; or
      (3) hyperplastic invasive. Some transient trauma induced resorptions require no
      treatment but must be carefully monitored to check that there are no complicating
      issues such as infection. In cases of trauma induced replacement resorption, a
      multidisciplinary approach is usually necessary to ensure an optimal long-term
      solution. Infection induced tooth resorptions require the removal of the invading
      micro-organisms by endodontic therapy including intra-canal medication which can
      also facilitate repair of the resorbed tooth structure. The hyperplastic invasive
      tooth resorptions pose considerable challenges in management due to the
      complexity and aggressive nature of the resorptive process. With careful case
      selection and complete inactivation of resorptive tissue successful management
      can be achieved.

PMID- 17546867
TI  - The endodontic management of traumatized permanent anterior teeth: a review.
AB  - Despite the many journal articles and reviews that have been published regarding
      the treatment of trauma to teeth, the endodontic management of these injuries is
      often still not fully understood. The purpose of this review is to establish
      clear and up-to-date guidelines for practitioners who are faced with treating
      dental injuries on a day-to-day basis, based on an assessment of current
      available scientific information relating to the endodontic management of these
      injuries. Treatment is discussed under the headings: infractions, uncomplicated
      crown fractures, complicated crown fractures, crown-root fractures, root
      fractures, luxation injuries, avulsion, root resorption, pulp canal obliteration
      and open-apex teeth. Emphasis is placed on the treatment of traumatized immature
      teeth where maintenance of pulp blood supply is important to encourage continued
      development of the root system. Only the treatment of traumatized permanent
      anterior teeth is reviewed. Information contained in this article is based on a
      review of the literature on dental trauma which involved a MEDLINE search using
      the key words "dental trauma" and the individual topics listed above. The
      guidelines produced by the International Association of Dental Traumatology, the
      American Academy of Pediatric Dentistry and the American Association of
      Endodontists were also reviewed and the recommendations contained in this paper
      are in concert with the major recommendations of these bodies.

PMID- 17546868
TI  - Implant or the natural tooth--a contemporary treatment planning dilemma?
AB  - An assessment of whether to rehabilitate a tooth requiring endodontic treatment
      or to replace it with a dental implant can often involve a challenging and
      complex decision-making process. This paper reviews the literature pertaining to
      both treatment modalities and identifies key issues that need careful
      consideration in planning the most appropriate course of care in a given clinical
      situation. A need to appreciate advances across both disciplines is highlighted,
      allowing the development of effective interdisciplinary evidence-based treatment
      strategies to maximize treatment outcome.

PMID- 17546869
TI  - [Applied microanatomic study of pudendal-thigh skin flap].
AB  - OBJECTIVE: To investigate the microanatomic basis of the pudendal-thigh flap and
      provide the anatomic basis for clinical application. METHODS: Skin
      microdissection of the pudendal regions was performed on 11 adult cadavers (22
      sides). Then, the clinical way was simulated to obtain the flaps, and the vessels
      and nerves contained in them were surveyed. After that, the tissues in the deep
      part were dissected, and the vessels and nerves were traced back to their
      origins. The notes were taken. RESULTS: The blood supply to the pudenal regions
      was plentiful and constant. The initiation point of the superficial external
      pudendal artery was 2.14+ 0.23 mm in diameter; one branch of it was the inguinal
      branch and the other branch was the perineal branch. Their diameters were
      1.38+0.34 mm and 1.21+0.24 mm. The initiation point of the posterior labial or
      scrotum arteries was 1.13+ 0.24 mm in diameter, and the lateral branch was 0.
      67+0. 33 mm in diameter. The anterior cutaneous branch of the obturator artery
      was 1.68+ 0.11 mm in diameter. The position of all the blood vessels was
      relatively constant, especially the external pudendal artery and the lateral
      branch of the posterior scrotal artery. Many of the blood vessels passed through
      the areas of the pudendum and the thigh, anastomosed with each other. Three
      groups of the vascular net passed through the upper, middle and lower parts of
      the flap. Three main groups of the innervation were as the following: the ramus
      femoralis nervi genitofemoralis, the cutaneous branches of the ilioinguinal
      nerve, and the post-nerve of the scrotum or the labia vulvae. CONCLUSION: The
      pudendal-thigh flap has an abundant blood supply, and its dissection is
      convenient with an easy incision; the donor site is covert. The pudendal-thigh
      skin flap has the following advantages for the sexual organ reconstruction: the
      skin flap can have a good sensation and a good shape, and the operative procedure
      is easy to perform.

PMID- 17546870
TI  - [Influence of pedicle length on perforator flap in hemodynamics].
AB  - OBJECTIVE: To study the influence of the pedicle length on the perforator flaps
      in hemodynamics. METHODS: Four mature swine (2 males, 2 females; weight, 23.0 +/-
      2.0 kg) were applied to the experiment. Two transverse abdominal skin flaps,
      based on the superior epigastric pedicle or its rectus abdominal muscle
      perforators, were designed; each swine was used as its own control. At 2 hours
      and 1, 2, 3 weeks postoperatively, the skin paddle perfusion and the blood stream
      velocity in the superior epigastric artery were measured by the Laser Doppler
      Flowmeter and the Color Doppler Ultrasound, respectively. Flap survival
      percentages were calculated by the grid method at 1 week postoperatively. The
      swine were euthanatized, and they underwent angiography at 3 weeks
      postoperatively. RESULTS: At 2 hours and 1 week after operation, edema of the
      perforator flaps with the superior epigastric pedicle was more severe than that
      of the skin flaps with the rectus abdominal muscle perforator, and the skin
      perfusion had a statistical difference between the two kinds of flaps (P<0.05).
      The skin paddle viability and the skin perfusion had no statistical difference
      after the first week postoperatively (P>0.05). At 2 hours and 1 week after
      operation, the blood stream velocity in the superior epigastric artery in the
      perforator flap with the superior abdominal artery pedicle was reduced, and there
      was a statistical difference between the two kinds of flaps (P<0.05); however,
      the velocity was almost the same after the first week postoperatively.
      CONCLUSION: The excessively long pedicle of the perforator skin flap may have an
      unfavorable influence on the flap perfusion, especially during the first week
      after operation, because of the vascular compromise during the dissection of the
      long pedicle. The blood vessel anastomosis at this level of the blood vessels may
      have no relationship with the perforator flap in hemodynamics. This study can
      also indicate that the ligation of the branches in the recipient vessels cannot
      make the perforator flaps overperfused.

PMID- 17546871
TI  - [Reestablishment of sensory function after greater auricular nerve implanted into
      flap for reconstruction of buccal defect in rabbits].
AB  - OBJECTIVE: To assess the sensory restoration after the greater auricular nerve is
      implanted into the flap to repair the buccal defect in rabbits. METHODS: Fifteen
      Japanese white rabbits, weighing 2.0-2.5 kg, were randomly divided into the
      experimental group (nerve implanted), the control group (nerve unimplanted), and
      the normal group (without any treatment). In the experimental and the control
      group, circular defects (2.0 cm x 2.0 cm) were constructed in the left cheek of
      the rabbits. Then, the cervical flaps (4.5 cm x 2.5 cm) were transferred and the
      great auricular nerve was implanted into the defects in the experimental group,
      and the flaps without any nerve were implanted into the defects in the control
      group. The subjects in the normal group were given no treatment. After 6 months,
      the nerve discharge, the HE staining, and the immunohistochemical method were
      used to assess the regeneration of the nerve fibers. RESULTS: The nerve discharge
      and the percentage of the different kinds of the nerve fibers in the experimental
      group (124.2 +/- 33.8 roots) were not statistically different from those in the
      normal group (138.4+/-20.4 roots, P>0.05), but significantly different from those
      in the control group (18.8+/-5.6 roots, P<0.05). In the center of the flap in the
      experimental group, the receptive field of the nerve fibers was identical to the
      implanting approach of the greater auricular nerve. The HE staining and the
      immunohistochemical staining showed that the density of the regenerated fibers in
      the center of the flap in the experimental group reached the normal level. There
      was no regenerated fibers in the control group. CONCLUSION: The great auricular
      nerve implanted into the cervical flaps has a good effect on reconstruction of
      the buccal defect in rabbits.

PMID- 17546872
TI  - [Anterolateral thigh perforator free flaps for reconstruction of head and four
      limb soft tissue defects after tumor resection].
AB  - OBJECTIVE: To investigate the method, effectiveness, and clinical application of
      the anterolateral thigh perforator free flaps for reconstruction of the soft
      tissue defects in the head and the four limbs after tumor resection. METHODS:
      From April 2004 to April 2006, 16 patients (13 males, 3 females; aged 26-72
      years) with the soft tissue defects in the head (9 patients) and the four limbs
      (7 patients) underwent reconstructive operations with the anterolateral thigh
      perforator free flaps after their tumor resection. The defects ranged in area
      from 8 cm x 6 cm to 20 cm x 13 cmin the head with the process of diseases from 6
      to 24 months, and the defects ranged in area from 10 cm x 7 cm to 21 cm x 12 cm
      in the four limbs with the process of diseases from 2 to 18 months. The technique
      for the anterolateral thigh perforator flap free grafting, the degree of the
      injury in the donor sites, and the appearance of the donor and recipient sites,
      and the influence on the anatomy and function in the both local sites were
      analyzed. RESULTS: In the 16 patients with the soft tissue defects in the head
      and the four limbs after tumor resection, 14 had a primary wound healing (Stage I
      ), and 2 had a delayed wound healing (Stage II). Fifteen flaps survived
      completely but two flaps had a partial failure. The flap appearance was good and
      smooth without any severe scarring, and there was a minimal effect on the
      function at the donor and recipient sites. CONCLUSION: Because of the less
      morbidity at the donor site, the better result at the recipient site, and the use
      of the anterolateral thigh perforator flap free grafting, this kind of the
      technique for reconstruction of the head and four-limb soft tissue defects after
      tumor resection is well acceptable.

PMID- 17546873
TI  - [Reconstruction of soft tissue defects in maxillofacial region using sternal head
      of sternocleidomastoid myocutaneous flap].
AB  - OBJECTIVE: To evaluate the preliminary etfect of using the sternal head of the
      sternocleidomastoid myocutaneous flap to reconstuct a defect in the maxillofacial
      region. METHODS: From May 2004 to September 2006, 5 male patients aged 23-34
      underwent the reconstruction for the defect in the maxillofacial region by using
      the sternal head of the sternocleidomastoid myocutaneous flap. Their defects were
      caused by an infection of the face, an injection of medicine in the mother's
      uterus or a scar or depressed abnormality left by an electric injury. The defects
      ranged in size from 5 cm x 3 cm to 9 cm x 6 cm. RESULTS: All the 5
      sternocleidomastoid myocutaneous flaps survived, with a little necrosis of the
      epidermis because of the venous return disturbance, but 2-3 weeks after operation
      the necrosis healed spontaneously with just a little scar formation around the
      flap. One patient had weakness in the left shoulder after operation, which almost
      recovered 6 months after operation. The postoperative follow-up for 1-6 months
      revealed that 1 patient had a little fat and clumsy appearance in the flap
      pedicle, 1 patient had an obvious scar at the operation site, but the 2 patients
      still felt satisfaction. The other 3 patients were satisfied with their good
      appearance at the operation sites. CONCLUSION: The sternal head of the
      sternocleidomastoid myocutaneous flap can be designed with more flexibility
      compared with the entire sternocleidomastoid myocutaneous flap. It can provide an
      enough tissue mass for restoring the defect. The sternal head of the
      sternocleidomastoid myocutaneous flap is an ideal tissue flap for restoring
      defects in the maxillofacial region.

PMID- 17546874
TI  - [Clinical application of groin skin and iliac bone composite graft in contracture
      of first web space and reconstruction of pollicis opponens function].
AB  - OBJECTIVE: To investigate the therapeutic effects of the groin skin and iliac
      bone composite graft on the repair of severe contracture of the first web space
      and one-stage reconstruction of the pollicis opponens function under the
      condition of no ideal muscle or tendon used. METHODS: From July 2003 to February
      2006, 5 patients (4 males, 1 females; age range, 20-38 years) with severe
      contracture of the first web space with loss of the pollicis opponens function
      were treated by the groin skin and iliac bone composite graft, with the clinical
      observation performed. The defect was caused by a crush injury in 3 patients, by
      an explosion injury in 1 patient, and by a wrist joint mutilation injury in 1
      patient. They all had been treated by operation at least once with a disease
      course of 6-24 months. The width and the angle of the first web space was 18 mm
      and 20 degrees on average. RESULTS: The followed-up for 6-12 moths revealed that
      all the flaps had a success. The pedicle of the groin skin and iliac bone
      composite graft was cut off after 3 weeks, and 8 weeks later there was a bone
      union between the imbedded bone block and the first and second metacarpal bones.
      There was no evidence that the imbedded bone block was deformed or absorbed. The
      width of the first web space was augmented by an average of 32 mm, the angle of
      the first web space was augmented by an average of 60 degrees. The pollicis
      opponens function recovered. CONCLUSION: It is relatively simple and reliable to
      repair the contracture of the first web space and reconstruct the pollicis
      opponens function in one-stage using the groin skin and iliac bone composite
      graft.

PMID- 17546875
TI  - [Clinical application of vasularisied anterolateral thigh fascial flap].
AB  - OBJECTIVE: To evaluate a modified anterolateral thigh fascial flap designed for
      the treatment of the soft tissue defects in the forearms and hands. METHODS: From
      September 2000 to December 2003, a modified anterolateral thigh fascial flap
      combined with the intermediate split thickness skin graft was applied to the
      treatment of 13 patients with the soft tissue defects in the forearms or the
      hands. There were 8 males and 5 females, aged 19-43 years (average, 27. 6 years).
      Three patients had a mangled injury, 4 had a belt injury, and 6 had a crush
      injury; 6 patients had their tissue defects on the palm side of the forearm, 6
      had their tissue defects on the dorsal side of the hand, and 1 had the defect in
      the index finger (dorsal side of the hand). The tissue defects ranged in size
      from 17. 5 cm x 7. 7 cm to 4. 6 cm x 3. 4 cm. In addition, 4 of the patients had
      an accompanying fracture in the forearm or the hand, and the remaining 9 had an
      extenor tendon injury. All the patients underwent emergency debridement and
      reposition with an internal fixation for the fracture; 3-5 days after the repair
      of the injured nerves, muscle tendons and blood vessels, the tissue defects were
      repaired with the anterolateral thigh fascial flap combined with the intermediate
      split thickness skin graft. RESULTS: No vascular crisis developed after
      operation. All the flaps survived except one flap that developed a parial skin
      necrosis (2.0 cm x 1.0 cm) in the hand, but the skin survived after another
      skingrafting. The follow-up for 3-12 months revealed that all the flaps and skin
      grafts had a good appearance with no contracture of the skin. According to the
      evaluation criteria for the upper limbs recommended by the Hand Society of
      Chinese Medical Association, 9 patients had an excellent result, 2 had a good
      result, I had a fair result, and 1 had a poor result, with a good/excellence rate
      of 85%. CONCLUSION: The modified anterolateral thigh fascial flap combined with
      the skin graft is one of the best methods for the treatment of the soft tissue
      defects in the forearms and the hands. This method has advantages of no
      requirement for a further flap reconstruction, no skin scar or contracture in the
      future, easy management for the donor site, and less wound formation.

PMID- 17546876
TI  - [Application of medial head gastrocnemius muscle flap to limb-salvage operation
      of proximal tibial malignant tumor].
AB  - OBJECTIVE: To evaluate the efficacy of transposition of the medial gastracnemius
      muscle flap in the limb-salvage operation of the proximal tibial tumors. METHODS:
      From January 2001 to September 2005, 13 patients (8 males, 5 females; aged 14-57
      years, averaged 29.7 years) suffering from the proximal tibial tumors were
      treated with a limb-salvage operation. Among them, there were 4 patients with
      osteosarcoma, 6 with malignant fibrous histocytoma, 1 with malignant giant cell
      tumor, 1 with synovial sarcoma, and 1 with Ewing's sarcoma. According to the
      Enneking staging system, 1 case was in Stage I B, 9 in Stage II A, and 3 in Stage
      II B. One or two cycles of neoadjuvant chemotherapy were used to each of the
      patients before operation. All of the patients underwent the medial head of the
      gastrocnemius muscle flap transposition to reconstruct the soft tissues after
      resection of the tumors and reconstruction of the bone defect by prothesis or
      bone-graft or the two methods combined. RESULTS: The follow-up for 7-47 months
      (average, 19. 2 months) in all the patients revealed that. there was no flap
      necrosis, no skin necrosis at the incision margins, and no infection or fracture
      of the implanted bone. The patient with malignant fibrous histocytoma died of
      systemic metastasis 20 months after operation. The patient with Ewing's sarcoma
      had a local tumor recurrence 18 months after operation; though treated with the
      focal cleaning and the bone cement filling, the patient still developed lung
      metastasis of the tumor 26 months after operation. The patient with osteosarcoma
      underwent amputation 12 months after operation because of the tumor recurrence.
      According to the function assessment by the Mankin system, there were 6 patients
      who had an excellent result, 4 had a good result, and 3 had a poor result, with a
      satisfaction rate of 77%. CONCLUSION: The flap transposition of the medial head
      of the gastrocnemius muscle can reconstruct the soft tissue defect, decrease the
      local complication rate and improve the clinical outcome of the limb salvage for
      the proximal tibia malignant tumor.

PMID- 17546877
TI  - [Clinical application of lower rotating point super sural neurocutaneous
      vascular].
AB  - OBJECTIVE: To explore the clinical effect of the lower rotating point super sural
      neurocutaneous vascular flap on the repair of the soft tissue defects in the
      ankle and foot. METHODS: From May 2001 to February 2006, 24 patients with the
      soft tissue defects in the ankle and foot were treated with the lower rotating
      point super sural neurocutaneous vascular flaps. Among the patients, 15 had an
      injury in a traffic accident, 6 were wringed and rolled by a machine, 1 was
      frostbited in both feet, 2 were burned, 25 had an exposure of the bone and joint.
      The disease course varied from 3 days to 22 months; 19 patients began their
      treatment 3-7 days after the injury and 5 patients were treated by an elective
      operation. The soft tissue defects ranged in area from 22 cm x 12 cm to 28 cm x
      12 cm. The flaps ranged in size from 24 cm x 14 cm to 30 cm x 14 cm, with a range
      up to the lower region of the popliteal fossa. The rotating point of the flap
      could be taken in the region 1-5 cm above the lateral malleolar. The donor site
      was covered by an intermediate thickness skin graft. RESULTS: All the 25 flaps in
      24 patients survived with a satisfactory appearance and a good function. The
      distal skin necrosis occurred in 1 flap, but healing occurred after debridement
      and intermediate thickness skin grafting. The follow-up for 3 months to 5 years
      revealed that the patients had a normal gait, the flaps had a good sense and a
      resistance to wearing, and no ulcer occurred. The two point discrimination of the
      flap was 5-10 mm. CONCLUSION: The lower rotating point super sural neurocutaneous
      vascular flap has a good skin quality, a high survival rate, and a large donor
      skin area. The grafting is easy, without any sacrifice of the major blood vessel;
      therefore, it is a good donor flap in repairing a large soft tissue defect in the
      ankle and foot.

PMID- 17546878
TI  - [Distally-based sural musculocutaneous flap for chronic calcaneal osteomyelitis].
AB  - OBJECTIVE: To investigate the clinical significance of the distally-based sural
      musculocutaneous flap for the treatment of chronic calcaneal osteomyelitis.
      METHODS: From January 2002 to October 2005, 7 patients (4 males, 3 females; age
      range, 15-68 years) were treated with the distally-based sural musculocutaneous
      flap, who had chronic calcaneal osteomyelitis after calcaneal fracture. After the
      radical debridement for all the nonviable and poorly vascularized tissues, all
      the chronic calcaneal osteomyelitis patients, who had suffered from open
      calcaneal fracture or closed calcaneal fracture, were treated with the open
      reduction, the internal fixation, and the bone graft. The ulcer lasted for 3-12
      months before diagnosis of osteomyelitis. The musculocutaneous flaps ranged in
      size from 8 cm x 4 cm to 12 cm x 7 cm and the muscle flaps ranged from 4 cm x 3
      cm to 6 cm x 5 cm. The donor defects were closed primarily in 5 patients and were
      resurfaced with the split-thickness skin graft in 2 patients. RESULTS: All the
      musculocutaneous flaps survived completely and all the wounds healed smoothly.
      All the patients followed up for 2-6 months had no recurrence of osteomyelitis or
      return to their preoperative ambulatory status. CONCLUSION: It is feasible to use
      the distally-based sural musculocutaneous flap for treatment of chronic calcaneal
      osteomyelitis.

PMID- 17546879
TI  - [Anatomical studies and clinical applications of distally-based intermediate
      dorsal neurocutaneous flap on the foot].
AB  - OBJECTIVE: To provide the anatomic basis for the design of the intermediate
      dorsal neurocutaneous flap on the foot and to report the clinical results.
      METHODS: On 32 adult cadaver lower limb specimens perfused with red latex, the
      origins, diameters, courses, branches, and distributions of the intermediate
      dorsal cutaneous nerve of the foot and its nutrient vessels were observed. On
      this anatomic basis, from June 2004 to October 2005, 5 flaps were developed and
      applied to the repair of the soft tissue defect in the feet of 4 patients.
      RESULTS: The intermediate dorsal cutaneous nerve of the foot was found to arise
      from the superficial peroneal nerve. Crossing the intermalleolar line, it was
      located 1.3+/-0.6 cm lateral to the midpoint of the line with a diameter of
      2.05+/-0.56 mm. The nerve stem divided into branches 2.8+/-1.3 cm distal to the
      line. They distributed the dorsal skin of the second, third and fourth metatarsal
      and toe. On average, 5. 1 perforators per specimen were identified. At least 3
      nutrient vessels were always found in each. They originated from the cutaneous
      branches of the anterior tibial artery and the dorsalis pedis artery in the
      proximal end and the dorsalis metatarsal artery in the distal end. They
      perforated the deep fascia 4.3+/-0.4 cm proximal to the intermalleolar, 1.6+/-0.3
      cm proximal to the tip of the third toe webspace and 1.5+/-0.3 cm proximal to the
      tip of the forth toe webspace, respectively. The external diameters of them were
      0.82+/-0.13, 0.42+/-0.07 and 0.49+/-0.09 mm, respectively. The patients were
      followed up for 4-10 months. All the flaps survived completely. Their appearance
      and function were satisfactory. CONCLUSION: The distally-based intermediate
      dorsal neurocutaneous flap on the foot has an abundant blood supply. This kind of
      flap is especially useful in repair of the soft tissue defect in the foot.

PMID- 17546880
TI  - [Management of soft tissue defect after achilles tendon repair].
AB  - OBJECTIVE: To investigate the management of the soft tissue defect after the
      Achilles tendon repair. METHODS: From April 1996 to April 2006, 24 patients (17
      males, 7 females; aged 16-59 years), who suffered from postoperative Achilles
      tendon exposure caused by local soft-tissue necrosis after the Achilles tendon
      repair, were treated and evaluated. Of the 24 patients, 8 had an original open
      injury (machine-crush injury in 2 patients, heavy-object press injury in 3, motor
      cycle wheel crush injury in 3) and 16 patients had a closed injury (sports
      injury). In their treatment, the transfer of the sural neurovascular flap was
      performed on 8 patients and the transfer of the saphenous neurovascular flap was
      performed on 3 patients. The secondary Achilles tendon repair was performed on 13
      patients before the neurovascular flap transfer was performed. The time between
      the injury and the operation was 9-76 days, and the time between the Achilles
      tendon expousure and the operation was 3-65 days. RESULTS: All the flaps survived
      and the Achilles tendon exposure was well covered by the flaps of good texture.
      Eighteen patients followed up for 6 months to 24 months had no flap complication,
      and the two point discrimination of the flaps was 12-20 mm. The AOFAS Ankle
      Hindfoot Scale assessment revealed that 8 patients had an excellent result, 6 had
      a good result, 3 had a fair result, and just 1 had a poor result, with the
      excellent and good results accounting for 77.8%. Sixteen patients (89%) were able
      to perform a tip-toe stance on their operative sides, and only 3 of them
      complained a loss of plantarflexion strength. However, 2 patients still could not
      perform the tip-toe stance. CONCLUSION: The Achilles tendon repair, if not well
      performed, can result in the local soft-tissue necrosis and the subsequent
      Achilles tendon exposure. If those complications occur, the neurovascular flap
      transfer should be performed as soon as possible; if necessary, the secondary
      Achilles tendon repair should be performed, too.

PMID- 17546881
TI  - [Treatment of cervicothoracic junction spinal lesions by modified anterior
      approach].
AB  - OBJECTIVE: To investigate the therapeutic effect of the modified anterior
      approach in treatment of the patients with cervicothoracic junction spinal
      lesions. METHODS: From September 2000 to January 2005, 23 patients (15 males, 8
      females) with spinal lesions in the cervicothoracic junction underwent a standard
      cervical approach, which was combined with a partial median steotomy and
      transverse steotomy through the synostosis between the manubrium and body of the
      sternum to expose the lesion adequately. Among the patients, 3 had fracture, 7
      had dislocation, 6 had tuberculosis, and 7 had tumor. The pathologic change
      regions was as follows: 2 in the C6-T1 segment, 2 in the C6-T2 segment, 3 in the
      C7-T1 segment, 3 in the T3 segment, 8 in the T1 segment, and 5 in the T2 segment.
      The classification of Frankel were as follows: 2 at grade A, 4 at grade B, 7 at
      grade C, 4 at grade D, and 6 at grade E. All the patients underwent a radical
      excision of the affected spinal bone, were given a proper tricortical iliac crest
      and anterior instrumentation to reconstruct the anterior spinal column, followed
      by immobilization in a brace for 3-6 months. RESULTS: The mean follow-up period
      was 30 months (range, 10-42 months). Bony fusion was obtained in all the
      patients. One patient died of pulmonary cancer metastasis 10 months after
      operation. The nerve function of the spinal cord recovered at different degrees
      (1 at grade A, None at grade B, 2 at grade C, 10 at grade D, 10 at grade E).
      CONCLUSION: Our modified anterior approach can provide a direct and safe access
      to the lesions in the region.

PMID- 17546882
TI  - [Treatment of lower cervical fracture dislocation by titanium screw-plate
      internal fixation on cervical lateral mass].
AB  - OBJECTIVE: To evaluate surgical results of the titanium screw-plate internal
      fixation in treatment of the lower cervical fracture dislocation. METHODS: From
      September 2001 to March 2006, 31 patients (24 males, 7 females; age range, 20-63
      years) with the lower cervical fracture dislocation were treated in our
      department. The injuries were caused by a road accident in 25 patients, a high
      crash in 4, and a heavy object crash in 2. The fracture dislocation occurred in
      the following cervical segments: C3 (1 patient), C1 (5 patients), C5 (12
      patients), C6 (10 patients), and C7 (3 patients). The disease course ranged from
      1 to 23 days. The associated spinal nerve root injury occurred in 29 patients.
      The Frankle scaling revealed that 14 patients were at Grade A, 3 at Grade B, 7 at
      Grade C, 3 at Grade D, and 2 at Grade E (associated nerve root injury with hand
      and shoulder numbness). The 29 patients underwent the spinal cord decompression,
      the grafting fusion of the small joints, and the lateral mass titanium screw
      plate internal fixation; 2 patients without nerve injury underwent only the
      grafting fusion of the small joints and the lateral mass titanium screw-plate
      internal fixation. The bone fusion, cervical vertebra movement, and internal
      fixation condition were observed by the X-ray examinations postoperatively. The
      nerve function recovery was evaluated by the Frankle scaling system. RESULTS: The
      followed-up in all the patients for 6 months to 4 years revealed that the small
      joint fusion time was 3-6 months, with an average of 3. 6 months. The cervical X
      ray films showed that there was no instability or fracture looseness of the
      internal fixation at 6 months. Among the 29 patients with the spinal nerve root
      injury, 14 were at Grade A preoperatively but 13 were improved at Grade B and 1
      at Grade C postoperatively; 3 were at Grade B preoperatively but 2 were improved
      at Grade C and 1 at Grade D postoperatively; 7 were at Grade C preoperatively but
      3 were improved at Grade D and 4 at Grade E postoperatively; 3 at Grade D
      preoperatively but all the 3 were improved at Grade E postoperatively; 2 were at
      Grade E preoperatively and remained unchanged postoperatively. In the 2 patients
      with only the nerve root injury, numbness disappeared soon after operation.
      CONCLUSION: This posterior approach has two advantages: the mobility range of the
      cervical vertebra can preserved to the greatest extent because of the short
      segment fixation; the better stability can obtained because of the titanium screw
      plate internal fixation on the cervical joint-column to prevent the
      hyperextension and hyperflexion. Therefore, the titanium screw-plate internal
      fixation on the cervical lateral mass is an effective treatment of the lower
      cervical fracture dislocation.

PMID- 17546883
TI  - [Comparative study on repair of medium and large-sized osteochondral compound
      defects with mosaicplasty].
AB  - OBJECTIVE: To investigate the effectiveness of mosaicplasty in repair of large
      sized osteochondral compound defects and the integrity of transplanted tissue
      with recipient sites so as to lay a foundation for clinical application. METHODS:
      Twenty-four adult goats were divided into 3 groups randomly. The diameters of
      defect were 6 mm for the medium-sized defects and 9 mm for the large-sized
      defects, which were created by a trepan. All of the defects were repaired with
      osteochondral plugs in diameters of 2 mm (the medium-sized defects) or 3 mm (the
      large-sized defects). The osteochondral plugs were harvested around the
      intercondylar fossa or intertrochlea groove, and pressed into the recipient sites
      by specialized instruments in a mosaic mode. No internal fixation was needed and
      the animal were allowed to move freely after operation. From 4 to 24 weeks
      postoperatively, the specimens were observed in gross and under
      electromicroscopy. X-ray detection and glycosaminoglycan (GAG) analysis were also
      performed to testify the healing process and the integrity of the cartilage and
      subchondral bone. RESULTS: The transplanted subchondral bone was integrated
      firmly with each other or with recipient sites in both mosaicplasty groups. But
      24 weeks postoperatively, transplanted cartilage was not integrate with each
      other apparently. Obvious cleavage between cartilage plugs could be seen. But in
      the large-sized defect groups, some of the osteochondral plugs were relapsed into
      the defects leaving the recipient sites some steps, leading to some degree of
      abrasion in the opposing articular cartilage. There was no significant difference
      in the GAG content between the transplanted cartilage and normal cartilage. X-ray
      analysis also demonstrated the healing process between the subchondral bone.
      CONCLUSION: Mosaicplasty can repair the medium or small-sized osteochondral
      defects efficiently.

PMID- 17546884
TI  - [Expression of vascular cell adhesion molecule 1 in acellular dermal matrix
      grafting in pigs].
AB  - OBJECTIVE: To explore the expression of the vascular cell adhesion molecule 1
      (VCAM-1) in the acellular dermal matrix grafting in pigs. METHODS: Experimental
      models were established with 15 Inbred Strain mini pigs, 6 full-thichness skin
      defect wounds, 6 cm x 6 cm in size, were produced on both-side backs of the each
      pig, and then the pigs were randomly divided into 3 groups. In Group A (n = 5,
      control) the thin auto-skin transplantation alone was made; in Group B (n = 5),
      the grafting was performed in the acellular allo-dermal matrix combined with the
      thin auto-skins; in Group C (n = 5), the grafting was performed in the acellular
      xeno-dermal matrix combined with the thin auto-skins. The areas of the wounds
      were measured and the survival condition of the grafted skins was observed at 3,
      9, 21 and 30 days after the grafting. The histological samples were harvested
      from the grafting area at 3, 6, 9, 12, 21 and 30 days after the procedure. The
      flow cytometry was employed to analyze the changes in the VCAM-1 level in the
      sample at different time points after the grafting. RESULTS: In the 3 groups, the
      transplanted skin base was easily separated at 3 days after transplantation; the
      areas of the wound healing accounted for 94Y+/- 12%, 92%+/- 9% , and 91%+/- 11%,
      respectively, at 21 days; good wound healing was achieved at 30 days. At 9 and 12
      days after transplantation, there was an evidently-increased level of the VCAM-1
      expression in the tissue samples in the composite skin grafting groups. Compared
      with the control group, the difference was significant (P < 0.05); however, the
      VCAM-1 expression at 3 days was not statistically different between the composite
      skin grafting groups and the control group after transplantation. In contrast,
      the level of the VCAM-1 expression was significantly higher at 6 days in the
      control group than in the composite skin grafting groups (P < 0.05). The levels
      of the VCAM-1 expression were significantly lower at 30 days than at 3 days after
      transplantation in all the 3 groups (P < 0.01). CONCLUSION: The highest level of
      the VCAM-1 expression can be delayed in the composite skin grafting when compared
      with that in the thin auto-skins alone, which implies that the VCAM-1 expression
      may be correlated with angiogenesis and composite skin survival. The VCAM-1
      expression is not different between the acellular allo-dermal matrix composite
      skin grafting groups and the acellular xeno-dermal matrix group.

PMID- 17546885
TI  - [Effect of platelet-rich plasma on proliferation and osteogenic differentiation
      of bone marrow stem cells in China goats].
AB  - OBJECTIVE: To explore the effect of the platelet-rich plasma (PRP) on
      proliferation and osteogenic differentiation of the bone marrow mesenchymal stem
      cells (MSCs) in China goat in vitro. METHODS: MSCs from the bone marrow of China
      goat were cultured. The third passage of MSCs were treated with PRP in the PRP
      group (the experimental group), but the cells were cultured with only the fetal
      calf serum (FCS) in the FCS group (the control group). The morphology and
      proliferation of the cells were observed by an inverted phase contrast
      microscope. The effect of PRP on proliferation of MSCs was examined by the MTT
      assay at 2, 4, 6 and 8 days. Furthermore, MSCs were cultured with
      dexamethasone(DEX)or PRP; alkaline phosphatase (ALP) and the calcium staining
      were used to evaluate the effect of DEX or PRP on osteogenic differatiation of
      MSCs at 18 days. The results from the PRP group were compared with those from the
      FCS group. RESULTS: The time for the MSCs confluence in the PRP group was earlier
      than that in the FCS group when observed under the inverted phase contrast
      microscope. The MTT assay showed that at 2, 4, 6 and 8 days the mean absorbance
      values were 0.252 +/- 0.026, 0.747 +/- 0.042, 1.173 +/- 0.067, and 1.242 +/-0.056
      in the PRP group, but 0.137+/-0.019, 0.436+/-0.052, 0.939+/-0.036, and 1.105+/
      0.070 in the FCS group. The mean absorbance value was significantly higher in the
      PRP group than in the FCS group at each observation time (P< 0.01). Compared with
      the FCS group, the positive-ALP cells and the calcium deposition were decreased
      in the PRP group; however, DEX could increase both the number of the positive-ALP
      cells and the calcium deposition. CONCLUSION: The PRP can promote proliferation
      of the MSCs of China goats in vitro but inhibit osteogenic differentiation.

PMID- 17546886
TI  - [Synergistic effect of fibronection and basic fibroblast growth factor on
      osteoblast adhesion efficiency].
AB  - OBJECTIVE: To investigate effects of the basic fibroblast growth factor (bFGF)
      and fibronection (FN) on the osteoblast adhesion on the bio-derived bone.
      METHODS: The third generation of the osteoblast was treated with bFGF 0. 1, 1,
      10, and 100 ng/ml, respectively, and then was seeded in the bio-derived bone,
      which had been modified with FN 0.1, 1, 10, and 100 microg/ml, or Polylysine,
      respectively. The cell adhesion was measured by the MTT assay. The cell density
      and the cell appearance were observed by the scanning electron microscope. The
      above-mentioned procedures were repeated by an application of the GRGDS peptide.
      RESULTS: Both FN and bFGF could enhance the osteoblast adhesion efficiency on the
      bio-derived bone (P < 0.05). However, the osteoblast adhesion efficiency could be
      significantly strengthened by a combined use of FN and bFGF. FN and bFGF had a
      significant synergistic effect in statistics (P < 0.01), but Polylysine and bFGF
      had no such synergistic effect (P > 0.05). The combined use of FN and bFGF had a
      better effect on the cell density and the cell appearance than either of them
      when observed with the scanning electron microscope. Adhesion efficiency
      generated by the combined use of FN and bFGF was significantly blocked by the
      application of the GRGDS peptide. CONCLUSION: The combined use of FN and bFGF has
      a significant synergistic effect on the osteoblast adhesion efficiency on the bio
      derived bone. This effect is probably mediated by the RGD-integrin alpha5beta1
      pathway.

PMID- 17546887
TI  - [Construction and identification of replication-defective recombinant adinovirus
      expressing human bone morphogenetic protein 4].
AB  - OBJECTIVE: To construct a replication-detective recombinant adinovirus including
      tne target gene human bone morphogenetic protein 4 (fragment hBMP-4). METHODS:
      The hBMP-4 gene fragment was cut down from pCS2(+)/hBMP-4, cloned into the
      eukaryotic expressive vector pcDNA 3.1(+), then subcloned into pShuttle-CMV and
      transformed into the competent E. coli BJ5183/p by electroporation. The resulting
      recombinant plasmid pAdE/ hBMP-4 was transformed into the packaging of the cell
      lines HEK293 to produce the replication-defective recombinant adenoviruses
      containing the hBMP-4 gene. These replication-defective recombinant adinoviruses
      were transfected into HEK293 and HeLa cells. Then, total RNA and total protein
      were detected by RT-PCR and the Western-blot assay. RESULTS: The pAdE/hBMP-4 was
      confirmed by the restrictional endonuclease digestion. In HEK293 and HeLa cells,
      the specific transcription of the hBMP-4 gene was confirmed by RT-PCR, and the
      expression of the hBMP-4 protein was confirmed by the Western-blot assay.
      CONCLUSION: The replication-defective recombinant adinovirus expression vector
      containing the hBMP-4 gene can be constructed and expressed successfully, which
      has laid a foundation for the further research on the genetherapy of hBMP-4.

PMID- 17546888
TI  - [Fabrication of collagen/sodium hyaluronate scaffold and its biological
      characteristics for cartilage tissue engineering].
AB  - OBJECTIVE: To develop a scaffold material containing collagen 1 and sodium
      hyaluronate for the cartilage tissue engineering and to evaluate its
      biocompatibility by using the rabbit chondrocytes derived from a mandibular
      condylar process. METHODS: The porous matrices containing collagen 1 and sodium
      hyaluronate were fabricated by the freeze-drying technique and were crosslinked
      by using 1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide (EDC). The
      microstructure of the scaffold was observed under the scanning electron
      microscope (SEM), and the enzymatic degradation test was performed to compare the
      ability of the scaffold resistance to collagenase before and after the
      crosslinking. The chondrocytes from the rabbits' condylar process were isolated
      and cultured before they were seeded into the scaffold, and cell attachment and
      proliferation were measured by the cell count 1, 3, 5, 7 and 10 days after the
      cell being seeded; then, the biocompatibility of the scaffold was evaluated by
      the light microscopic examination, histological examination, and the SEM
      exmination. RESULTS: The porous structure of the scaffold facilitated the
      penetration and attachment of the seeded cells. The porosity was 83.7% and the
      pore size was 100-120 microm. The cell number increased from 3.7 x 10(4) per
      scaffold 1 day after the cell being seeded to 8.2 x 10(4) per scaffold 10 days
      after the cell being seeded. The crosslinking treatment could significantly
      enhance the scaffold resistance to the collagenase activity. The examinations
      under the light microscope and SEM indicated that the chondrocyte adhered and
      spread well on the scaffold, and the extracellular matrices were also observed
      around the chondrocytes. CONCLUSION: The porous scaffold composed of collagen I
      and hyaluronan has an appropriate structure and a good biocompatibility for the
      attachment and proliferation of the chondrocytes, which can facilitate it to
      become a useful scaffold in the cartilage tissue engineering.

PMID- 17546889
TI  - [Fast reconstruction of composite tissue-engineered skin in vitro].
AB  - OBJECTIVE: To find a feasible method that can reconstruct the composite tissue
      engineered skin fast in vitro and can provide enough skin as soon as possible for
      covering the surface of the large-area burn. METHODS: The foreskin was taken
      during the posthectomy. The epidermal cells and fibroblasts were isolated,
      identified and cultured. The cytokeratin 19 (K19) flow cytometry and the
      fluorescein isothiocyanate (FITC)-immunofluorescence for K19 and the FITC
      immunofluorescence for PAN-cytokeratin of the epidermal cells and the FITC
      immunofluorescence for vimentin of the fibroblasts were performed to identify the
      epidermal cells and the fibroblasts. Then, the epidermal cells were seeded onto
      the papillary surface of an acellular dermal matrix (ADM) and were submerged into
      the condition culture medium added with 25 ng/ml of the keratinocyte growth
      factor (KGF). However, in the control group, no KGF was added. After 24 hours,
      the ADM was moved up to the air-fluid surface, and the culture was continued.
      After 6 days, the fibroblasts were seeded onto the other surface of the ADM.
      After a 24-hour culture, the ADM was harvested and fixed in formalin, and the
      hematoxylin-eosin staining was conducted. Then, the structure of the
      reconstructed skin was observed under the microscope and the cell count in the
      epidermal layer was also conducted. RESULTS: All the cultured and expanded
      epidermal cells stained by the immunofluorescence demonstrated a positive
      reaction for PAN-FITC, and a partially positive for K19-FITC, and 17% of the
      cells demonstrated a positive reaction for K19 identified by the flow cytometry.
      The fibroblasts could be expanded by more than 100 times after a 7-day culture in
      vitro, and they could demonstrate a positive reaction for vimentin-FITC. After a
      7-day culture, a composite tissue-engineered skin could be attained. The
      hematoxylin-eosin staining of the reconstructed skin showed that there was one
      continuous layer of the epidermis on the papillary surface of the ADM and there
      were fibroblasts in the superficial layer of the other one, but the epidermal
      layer did not stick tightly to the ADM. The cell count demonstrated that KGF
      promoted the epidermal cells to proliferate better (P<0.01) and to form more
      significantly continuous layers of the epidermis in the experimental group than
      in the control group (P < 0.01). CONCLUSION: Through the seed-cell separation by
      the digestion of collagenase and trypsin combined with the use of the KGF-added
      condition culture medium, a composite tissue-engineered skin can be reconstructed
      within 7 days.

PMID- 17546890
TI  - [Application of electrostatic spinning technology in nano-structured polymer
      scaffold].
AB  - OBJECTIVE: To review the latest development in the research on the application of
      the electrostatic spinning technology in preparation of the nanometer high
      polymer scaffold. METHODS: The related articles published at home and abroad
      during the recent years were extensively reviewed and comprehensively analyzed.
      RESULTS: Micro/nano-structure and space topology on the surfaces of the scaffold
      materials, especially the weaving structure, were considered to have an important
      effect on the cell adhesion, proliferation, directional growth, and biological
      activation. The electrospun scaffold was reported to have a resemblance to the
      structure of the extracellular matrix and could be used as a promising scaffold
      for the tissue engineering application. The electrospun scaffolds were applied to
      the cartilage, bone, blood vessel, heart, and nerve tissue engineering fields.
      CONCLUSION: The nano-structured polymer scaffold can support the cell adhesion,
      proliferation, location, and differentiation, and this kind of scaffold has a
      considerable value in the tissue engineering field.

PMID- 17546891
TI  - [Experimental studies of adenoviral-mediated exogenous gene transfer to donor
      heart].
AB  - OBJECTIVE: To study efficiency and security of the recombinant adenoviral
      mediated gene transfer to the donor heart during the heart transplantation.
      METHODS: A total of 140 healthy male Wistar rats, aged 10 weeks, weighing 200-250
      g, were equally divided into the donor group and the recipient group, and then 70
      rats in the recipient group were randomly and equally divided into 2 subgroups:
      the gene transfer group and the control group. The rat model of heterotopic heart
      transplantation(Abdomen)was developed, the donor hearts were removed and their
      coronary arteries were perfused with 800 microl of the recombinant adenoviral
      vectors encoding the beta-galactosidase gene (Ad-LacZ). The grafts were stored in
      the 4 C cold saline solution for 30 minutes, and then the syngeneic transplant
      was performed. In the control group, saline of tales doses was perfused. The
      donor hearts were harvested at 3, 5, 7, 14, and 28 days (n = 7) after
      transplantation, and the beta-galactosidase activity was assessed by the X-gal
      staining. At 28 days the major organs of the recipients were tested by the
      histopathological analysis and the polymerase chain reaction of the adenoviral
      E1A sequences. RESULTS: The successful gene transfer of the beta-galactosidase
      gene was demonstrated in the adenovirus-perfused hearts, with no staining in the
      control group. The gene expression reached a peak level at 3, 5 and 7 days, and
      the averaged numbers of the total beta-galactosidase positive staining cells per
      slice were 66.4 +/- 23.1, 91.3 +/- 32.4 and 68.7 +/- 22.7, respectively, with no
      significant difference between the groups (P > 0.05). At 14 days the gene
      expression gradually declined (32.1+/-13.9), and the significant difference was
      found when compared with that at 3, 5 and 7 days (P< 0.05). At 28 days the cells
      positive for beta-galactosidase were sparse (3.9 +/- 3.4), and the gene transfer
      was significantly less efficient compared with that at 3, 5, 7 and 14 days
      (P<0.05). The major organs of the recipients were not affected seriously at 28
      days. No virus spread to other organs in this experimental protocol. CONCLUSION:
      The ex vivo adenoviral-mediated gene transfer intracoronarily to the donor heart
      during the heart transplantation is feasible and safe.

PMID- 17546892
TI  - [Novel magnetic rings for rapid large vascular reconstruction in canine liver
      transplantation model].
AB  - OBJECTIVE: To investigate an improved large vascular reconstruction method in the
      canine liver transplantation and see whether it can shorten the anheptic time and
      thus reduce the harmful effects during the anhepatic phase. METHODS: Thirty-two
      mongrel dogs were enrolled and divided into two groups randomly:the donor group
      (n= 16) and the acceptor group (n = 16). The dogs in the acceptor group were
      divided into two groups, according to the different reconstruction methods: Group
      A using the magnetic rings for a large vein reconstruction in the canine liver
      transplantation (n = 10), and Group B using a hand-sewing large vein
      reconstruction in the canine liver transplantation (n = 6). The operation time,
      hemodymics change, anastomosis site, and survival were observed. RESULTS: The
      operation time was as follows: In Group A, the total operation time, the inferior
      vena cava anastomosis time, and the anheptic phase time were significantly
      shorter than those in Group B (3.24+/-0.49 h vs 4.12+/-0.51 h, 5.89+/-2.27 min vs
      28.33+/-6.04 min, 3.89+/-0.73 min vs 12.16+/-3.72 min),with a significant
      difference between the two groups (P< 0.01). The haemodymics changes were as
      follows: In Group A, MAP dropped during the anhepatic phase, but it soon
      recovered after reperfusion, and there was only 730.56+/-150.56 ml of fluid
      including the donor blood that needed to be transfused, with no pressor agent
      required. In Group B, blood pressure dropped during the anhepatic phase, but it
      slowly recovered,and there was 2241.67+/-390.78 ml of fluid. In Group A, all the
      stomas had no errhysis, twist or thrombus. The twisted stomas could be corrected
      by the revolving of the magnetic rings. The endangium at the site of anastomosis
      was smooth. In Group B, most of the stomas had errthysis. In Group A, 3 dogs
      survived for more than 7 days, 6 dogs survived for 3-6 days, and 1 dog survived
      for only 12 hours. In Group B, 2 dogs survived for 3-6 days, 3 dogs survived for
      1-2 days, and 1 dog survived for only 12 hours. CONCLUSION: Using the magnetic
      rings for a large vascular reconstruction in the canine liver transplantation is
      an improved method, which can simplify the anastomosis procedures and
      significantly shorten the anheptic phase time. However, the magnetic rings have
      to be placed in the abdomen, so this method remains to be further improved.

PMID- 17546893
TI  - [Application of autologous platelet-rich gel to refractory chronic diabetic
      cutaneous ulcers].
AB  - OBJECTIVE: To review and evaluate the clinical application of autologous platelet
      rich gel (APG) in refractory chronic diabetic cutaneous ulcers. METHODS: The
      latest literature was extensively reviewed, and the potential mechanism of APG
      for healing diabetic cutaneous ulcers was discussed. RESULTS: APG accelerated the
      ulcer healing, especially in healing the refractory diabetic cutaneous ulcers,
      and the high-level growth factors from the platelet releasate were thought to be
      the major potential mechanism of the APG action. CONCLUSION: APG can promote the
      healing of refractory chronic diabetic cutaneous ulcers. Topical haemotherapy
      with APG may be considered an adjuvant treatment of a multidisciplinary process
      and may be useful to the effective therapy of cutaneous ulcers.

PMID- 17546894
TI  - [Epidemiology of oral cancer].
AB  - In Hungary, the mortality rate from oral cancer is dramatically increasing,
      causing great concern. Smoking, drinking and poor oral hygiene are the major risk
      factors, and their combined effect could only be prevented by primary preventive
      measures in a long time period and therefore the benefit from primary prevention
      can be detected much later. The possibilities of the secondary preventive
      measures are much better to identify the premalignant conditions and lesions for
      these cancers. Screening could be used to detect both precancerous lesions and
      early invasive cancers, however, no study as yet has demonstrated a reduced
      mortality from screening, therefore, sui generis regular, organised screening,
      based on personal call-and-recall system, is not recommended. In the same time,
      regular opportunistic screening by clinical examination, i.e. visual inspection,
      using dental mirror, and palpation of the region in asymptomatic persons at high
      risk offers prime opportunity for early detection and early treatment. Recently,
      the government has decided to take action by promoting the clinical examination.
      To this effect, a Working Group consisting of subject experts and headed by the
      Chief Medical Officer has been appointed and charged with elaboration of a
      workable plan of action. In terms of action, priority',should be given to men and
      women above 40 years of age who are heavy smokers and drinkers; socioeconomic
      differentials should be taken into account. In the first place, dentist-patient
      encounters provide opportunity for such an examination, but primary care
      physicians and those engaged in occupational medicine are also requested to take
      part in the endeavour. As a prerequisite, the screening method needs to be
      incorporated in the curriculum of dental/medical education. From all these, the
      oral cancer-related epidemiological situation is expected to improve in Hungary.

PMID- 17546895
TI  - [Diagnostic value of radiographic and ultrasonic examinations in patients with
      sialoadenitis and sialolithiasis].
AB  - PURPOSE: The aim of this study was to evaluate diagnostic role of the native x
      ray and ultrasonography (US) in sialoadenitis and sialolithiasis. MATERIALS AND
      METHODS: During a period of 30 months 52 patients were selected in a study group
      with lithiasis and adenitis of the major salivary glands. Panoramic and either
      occlusal plain radiographs (sublingual and submandibular cases) or
      anteroposterior "blowed out" bucca and intraoral bucca radiographs (parotid
      cases), and US were taken of all patients. Further investigations, such as CT,
      MRI or FNAB were performed to discover probable differential diagnostic problems.
      RESULTS: The sensitivity of US for salivary stones was 75.0%, for inflammation
      was 77.4%. The sensitivity of x-ray for salivary stones was 60.7%. The cumulative
      effectiveness of x-ray and US for sialolithiasis was 91.3%. In the remaining two
      cases of sialolithiasis, CT supported the earlier diagnosis. In sialoadenitis,
      twice FNAB, four times MRI verified the supposed diagnosis. CONCLUSIONS: Despite
      the advantages of CT and MR evaluations, sonography and native x-ray seems to
      keep their priorities as diagnostic methods, because they are cost-effective and
      easily available in dento-alveolar surgical practice. The lack of intraductal
      imaging ability might be considered as one of the major disadvantages in
      evaluation of possible diagnostic alternatives.

PMID- 17546896
TI  - [The prevalence of oral mucosal lesions in Hungary].
AB  - The aim of the survey was to recognize the lesions of the oral mucosa (any
      alterations from healthy normal tissues) related to gender, age, intraoral
      localization, geographic regions, according to smoking habits and dental surgery
      attendance, based on the data of "Epidemiological national survey on oral health
      2003-2004.". In the nationwide survey 4606 people (2923 women, 1683 men)
      participated. Oral mucosal lesions registered in 10.14 and 9.41% in males and
      females (respectively). The highest prevalence of mucosal lesions occurred in 45
      64 year old age group. The highest number of the oral lesions was found in the
      buccal mucosa in males (42%). In females the most of the lesions are registered
      on the hard palate (24%) and on the buccal mucosa (24%). By geographic regions
      the highest prevalence of oral mucosal lesions occurred in "Kozep-Dunantul"
      statistical region, and the lowest prevalence was found in "Del-Dunantul".
      Statistically significant correlation could be shown between prevalence of oral
      mucosal lesions and smoking habits (p < or = 0.05) and there was a significant
      correlation between the frequency of dental surgery attendance and the prevalence
      of mucosal lesions in the examined population. The data of this epidemiological
      study could serve a good base for planning of preventive programs in different
      populations in the future.

PMID- 17546898
TI  - [Orthodontic treatment possibilities of allergic patients].
AB  - During the past two decades the incidence of allergies against dental materials
      has been rising. The most common allergens are nickel, mercury, benzoxyl
      peroxide, formaldehyde, MMA, HEMA, EGDMA and TEGDMA. Contact allergy develops in
      predisposed individuals as a consequence of environmental exposures to allergens.
      Although the relatively high frequency of contact allergies in children is well
      documented, its importance during orthodontic treatments is still often
      underestimated. The most common metal to cause dental allergic reactions is
      nickel. Nickel-containing metal alloys, such as nickel-titanium, are widely used
      in orthodontics because of their favorable physical properties. Coated wires
      (epoxi coating, teflon, etc.) are not only more aesthetic, but can play a role in
      the orthodontic treatment of patients with nickel allergy. In our case report we
      present two patients with nickel allergy, and their treatment with alternative
      orthodontic appliances. During the orthodontic treatment our patients did not
      have any objective or subjective allergy-related symptoms.

PMID- 17546897
TI  - [Mixed odontogenic tumors in children and adolescents].
AB  - Mixed odontogenic tumors in the jaws of children and adolescents usually cause
      dentition anomalies. The typical forms of these are ameloblastic fibroma,
      ameloblastic fibroodontoma, complex odontoma and compound odontoma. In the
      present study mixed odontogenic tumor cases are presented in patients under 20
      years of age. All of them were associated with tooth eruption disturbances.
      Further aim of this study was to discuss the nature and interrelationships of
      this group of lesions. Ameloblastic fibromas (AFs) are true, mixed, soft tissue
      neoplasms, deriving from the proliferation of both odontogenic epithelium and
      mesenchyma. They have a potential to both recurrence and malignant
      transformation. Ameloblastic fibroodontomas (AFOs) may be regarded as hamartomas,
      which exhibit epithelial, mesenchymal and abundant hard tissue components of the
      developing teeth. Odontomas are calcifying benign hamartomas, and represent the
      most common type of odontogenic jaw tumors among patients less than 20y, having
      complex and compound variants. Complex odontomas (CXOs) are built up from
      amorphous hard tissue elements, and generally occur in the premolar or molar
      regions of the maxilla. Compound odontomas (CDOs) usually appear in the maxilla,
      in the region of the incisors and canines, and contain small, radio-opaque
      structures reminiscent of rudimentary teeth. Early diagnosis and treatment of
      mixed odontogenic jaw tumors in children may prevent the serious orthodontic
      complications and jaw deformations.

PMID- 17546899
TI  - [Possible methods for evaluating bone density in the maxillofacial region].
AB  - Bone densitometry is a commonly used procedure in general medicine to measure the
      mineral content of the bone. The method helps in establishing an early diagnosis
      of metabolic diseases of the bone (especially osteoporosis), which decreases the
      incidence of pathological fractures in a high degree. Recent studies have shown
      that significant correlation can be found between the optical densitometric
      evaluations of the jaws and the densitometric figures of other bones of the
      skeleton (spine, hip). These results point out the possible role of the dentist
      in the early diagnosis of osteoporosis. The recent methods in general medicine
      are based on the measurement of photon and x-ray absorption followed by
      computerized analysis (single photon absorptiometry, single energy x-ray
      absorptiometry, dual photon absorptiometry, dual energy x-ray absorptiometry).
      Besides the previously mentioned techniques ultrasound attenuation detection
      (quantitative ultrasound) and computed tomographic approaches are also widely
      spread. Methods utilizing the developed panoramic x-ray films are also being used
      for densitometric evaluations. The results given by these measurements seem to be
      promising as a unique detection of the early signs of osteoporosis.

PMID- 17546900
TI  - Unconditional compensation: reducing the costs of disagreement about compensation
      for research subjects.
AB  - A central requirement of research involving humans is that people who participate
      as subjects should do so voluntarily. We argue that disagreements about the
      effect of offers of compensation on subjects' ability to participate voluntarily
      are likely to persist and to have high social costs. We propose a novel
      compensation practice--to pay potential subjects whether or not they participate-
      and argue that its implementation in some regions, including the Eastern
      Mediterranean Region, may reduce disagreement and thus mitigate such costs. We
      outline a research programme for assessing the potential of this practice to
      reduce costs.

PMID- 17546901
TI  - Climatic variables and transmission of falciparum malaria in New Halfa, eastern
      Sudan.
AB  - The study investigated the role of climatic variables and irrigated agricultural
      on the seasonality of malaria transmission in New Halfa, eastern Sudan. A time
      series analysis was performed using monthly climatic variables, monthly water
      available for irrigation of crops and monthly slide positive rate of malaria
      during the period 1986-2002. Cases of malaria were reported every month of the
      year with a mean of 13.0/100 persons/month (95% CI: 11.9-14.2), and bimodal
      annual pattern in autumn and winter seasons. Rainfall was the significant
      climatic variable in the transmission of the disease, whereas heavy rainfall was
      found to initiate epidemics. Temperature, relative humidity and irrigation water
      were not significant factors.

PMID- 17546903
TI  - Malaria signs and infection rate among asymptomatic schoolchildren in Hajr
      Valley, Yemen.
AB  - This study recorded malaria signs and the rate of parasitaemia among asymptomatic
      schoolchildren in Hajr valley, Hadhramout governorate, Yemen. Tests were made for
      malaria parasites and anaemia in 469 randomly selected primary-school children
      aged 6-11 years, together with clinical examination to determine spleen size, and
      interviews to study sociodemographic factors. Of the children, 12.8% had positive
      malaria blood films and 11.3% had spleen enlargement. There were significant
      associations between malaria infection, anaemia and splenomegaly and fever.
      Children with malaria parasitaemia were more often absent from school.

PMID- 17546902
TI  - Efficacy of chloroquine and sulfadoxine/pyrimethamine mono- and combined therapy
      against falciparum malaria in Sudan.
AB  - We assessed the efficacy of chloroquine and sulfadoxine/pyrimethamine monotherapy
      in several sentinel sites in northern Sudan and the efficacy of combined therapy
      in 2 sites. Chloroquine efficacy in children under 5 years was also assessed in 2
      sites in southern Sudan. Patients with indications of uncomplicated falciparum
      malaria and sufficient parasite density were enrolled. The chloroquine failure
      rates in the northern and southern sites were 43.4% and 80.2% respectively.
      Treatment failure was significantly higher in children than adults, while there
      was no significant sex difference. Sulfadoxine/pyrimethamine had an overall
      failure rate of 4.4%. Combination of the 2 drugs had a failure rate of 14.5% and
      5.9% in the 2 sites.

PMID- 17546904
TI  - Human cystic echinococcosis in nomads of south-west Islamic Republic of Iran.
AB  - We investigated the prevalence of human CE among nomadic communities in 4 areas
      of Khuzestan province: Behbahan, Shoush, Masjed Soleiman and Izeh. Blood samples
      from 3446 individuals from 700 randomly selected families were examined for
      detection of antibody against Echinococcus granuIosus. Family members were
      interviewed to assess possible risk factors for infection such as age, sex, dog
      ownership. The prevalence of CE was 13.8%: 1.9% in Behbahan, 12.4% in Shoush,
      17.3% in Masjed Soleiman and 18.2% in Izeh. These differences were statistically
      significant. There was no significant association between CE seropositivity and
      age, sex and dog ownership.

PMID- 17546905
TI  - Antibiotic-resistant Salmonella spp. from human and non-human sources in Oman.
AB  - We investigated the antibiotic resistance of various strains of Salmonella
      isolated from different sources in Oman, namely sewage water, chicken and food
      handlers. Of 1242 isolates from food handlers, 15 (1.2%) were resistant to one or
      more antibiotic. Of these, 41% were resistant to ampicillin, 42% to co
      trimoxazole and 22% to chloramphenicol. None of the isolates was resistant to
      ciprofloxacin. Of 515 isolates from chicken and 432 from sewage water, 23.7% and
      14.1% respectively were resistant to one or more antibiotic. Susceptibility to
      the different antibiotics varied but none of the isolates from chicken was
      resistant to amikacin.

PMID- 17546906
TI  - [Prevalence and risk factors for nosocomial infections in Hassan II University
      Hospital, Fes, Morocco].
AB  - We determined the prevalence and risk factors for nosocomial infection at Hassan
      II University Hospital and the causative microorganisms among 282 inpatients. The
      mean duration of hospitalization was 16.4 (SD = 15) days. The prevalence of
      nosocomial infection was 6.7%. Infections at the site of the operation were the
      commonest. No catheter-related infection was noted. The main organisms isolated
      were Escherichia coli, Klebsiella pneumoniae and Candida albicans. The occurrence
      of a nosocomial infection was significantly associated with surgical operation (P
      = 0.005), presence of urinary catheter (P = 0.002) and length of hospital stay
      greater than 3 weeks (P = 0.04).

PMID- 17546907
TI  - Infective endocarditis at a tertiary care centre in Saudi Arabia: review of 47
      cases over 10 years.
AB  - To describe the pattern of infective endocarditis in a tertiary hospital in
      Riyadh, Saudi Arabia, a retrospective review was made of all cases admitted
      between 1993 and 2003. Of 47 patients, a native valve was involved in 37 (78.7%)
      and a prosthetic valve in 10 (21.3%). Predisposing cardiac conditions were
      present in 27 patients: rheumatic and congenital heart disease were the most
      common. Blood cultures were positive in 76.4% of patients: the most commonly
      isolated organisms were Staphylococcus spp. in 20 patients (12 Sta. aureus and 8
      coagulase-negative staphylococci) and Enterococcus spp. (6 patients). The
      complication rate was 78.7% and hospital mortality rate was 8.5%.

PMID- 17546908
TI  - [Diagnosis of pulmonary tuberculosis: evaluation of the TB IgA EIA assay in
      Morocco].
AB  - We analysed 2 evaluation lots of the TB IgA EIA test in pulmonary tuberculosis
      patients (TBp). Sera were obtained from 345 TBp, 18 healthy subjects (HS), 28
      subjects in contact with tuberculous patients (CS) and 16 non-tuberculous lung
      disease patients (N-TB) for the first evaluation lots and 302 TBp, 60 HS, 21 CS
      and 18 N-TB for the second. IgA titres against p-90 antigen with the second
      evaluation lot were significantly higher than the first evaluation lot. With the
      second evaluation lots, the sensitivity was 78.8% whereas with the first
      evaluation lot, the sensitivity was 75.9%. Specificity for the first and second
      evaluation lots was 50% and 70.7% respectively. The sensitivity of this test is
      still not satisfactory to establish pulmonary tuberculosis diagnosis.

PMID- 17546909
TI  - Platelet storage time and cytokine (IL-2R, IL-8, TNF-alpha) levels.
AB  - This study investigated whether cytokine accumulation in plasma of platelet
      concentrates obtained from single apheresis donors was beyond the acceptable
      limits of white blood cell contamination at different storage time-points.
      Samples were obtained from 11 voluntary apheresis donors. All products were
      heavily contaminated with leukocytes. Sampling times from stored platelets were
      0, 1, 3, 5 days respectively. Platelet, white blood cell counts and cytokines (IL
      2R, IL-8 and TNF-alpha) were measured. The study found significant cytokine
      accumulation during 5 days of storage time in leukocyte contaminated platelet
      concentrates, suggesting that the platelet storage time has an effect on IL-2R
      levels.

PMID- 17546910
TI  - [Demographic factors influencing hepatitis B and C infection in Benghazi, Libyan
      Arab Jamahiriya].
AB  - We studied the epidemiology of hepatitis B and C infection among a sample of
      patients referred to the Department of the Infectious and Endemic Diseases at Al
      Jamahiriya Hospital in Benghazi. Of a total 3250 patients, 40% were randomly
      selected. Of these, 51.2% were infected with hepatitis B virus, 46.9% with
      hepatitis C virus and 1.9% with hepatitis B and C. Younger patients and single
      patients were more prone to hepatitis B infection, while older patients, married
      patients and travellers were more prone to hepatitis C. About 20% of hepatitis B
      cases and 25% of hepatitis C cases were non-Libyans. Males were more affected
      (65%) than females (35%).

PMID- 17546911
TI  - Prevalence of antibodies to hepatitis E virus among male blood donors in Tabriz,
      Islamic Republic of Iran.
AB  - Serum samples from 399 voluntary male blood donors were tested for anti-hepatitis
      E virus (HEV) IgG during July and August 2004 at a blood transfusion centre in
      Tabriz city. The prevalence of anti-HEV IgG was 7.8% (95% CI: 5.2-10.4). Risk
      factors for infection included age and a low educational level. Seroprevalence
      increased significantly with age, from 3.3% in subjects under 30 years of age to
      37.5% in individuals 50 years and over. Illiterate individuals were at
      significantly higher risk for infection than educated persons. The high
      seropositive rate among our male blood donors is compatible with endemicity of
      HEV in the Islamic Republic of Iran.

PMID- 17546912
TI  - Primary health care emergency services in Abha district of southwestern Saudi
      Arabia.
AB  - To study emergency services delivery in all 30 primary health care centres in
      Abha district of Asir region, Saudi Arabia, data were collected about equipment
      and facilities, physicians' practices and attitudes, and patients' utilization of
      and satisfaction with emergency services. Two centres had no devoted place for
      emergency services. Lack of some essential equipment and drugs was evident. The
      greatest continuing medical education need for doctors was the management of
      cardiovascular emergencies (72.3%). Many doctors (40.4%) did not consider the
      majority of cases as true emergencies. Many patients (43.7%) used the centres for
      emergency services, the most common being trauma, burns and orthopaedics (47.8%).
      Most patients were satisfied overall with emergency services (82.2%).

PMID- 17546913
TI  - Epidemiology of hospitalized female burns patients in a burn centre in Shiraz.
AB  - During 2000 to 2001, all 170 female burn patients admitted to the Ghotbeddin Burn
      Centre in Shiraz were studied to determine the epidemiological characteristics
      and outcome of burn for these patients. The overall mortality rate was 64%. The
      highest frequency of burns (53.5%) occurred among 16-25-year-olds. The commonest
      cause of burn was flame (98.2%). The mean (SD) length of hospital stay was 13
      (14.3) days. Mean (SD) of total body surface area (TBSA) burned among all
      patients was 56% (28.5%); among those who survived it was 29% (13.4%) and among
      those who died it was 72% (21.7%). The relation between TBSA and mortality was
      statistically significant.

PMID- 17546914
TI  - Determinants and causes of son preference among women delivering in Mansoura,
      Egypt.
AB  - This study in Egypt, measured the son preference index, its determinants, and
      impact on reproductive behaviour and intention of 400 mothers attending for
      delivery. Overall son preference index was 1.4. The causes of sex preference were
      mainly psychological and social. Mothers with only girls were 496 times more
      likely to prefer a son as compared to those with boys only. Mothers with
      illiterate husbands were nearly 10 times more likely to prefer a son than those
      married to highly educated husbands. Achievement of the desired sex, whether son
      or daughter, was associated with less desire for more children, intention to
      prolong pregnancy spacing and intention to use contraceptives.

PMID- 17546915
TI  - Preregistration programme for medical practice: a survey of Cypriot trainees
      (2000 and 2002).
AB  - This paper reports the attitudes of medical school graduates participating in the
      preregistration training programme in Cyprus. There were 2 independent samples,
      one in the year 2000 of 34 trainees and one in 2002 of 45 trainees. The trainees
      responded to 45 statements of attitude on a 5-point Likert scale covering 3
      areas: workload, educational environment and lifestyle issues. The sample means
      for each statement were reported in both years and differences between the 2
      years were analysed. In general, the trainees had an overall neutral to negative
      attitude towards the programme in both years and there was little change over the
      2 years.

PMID- 17546916
TI  - Accreditation of hospitals in Lebanon: a challenging experience.
AB  - The quality of hospital care in Lebanon has witnessed a paradigm shift since May
      2000, from a traditional focus on physical structure and equipment to a broader
      multidimensional approach, emphasizing managerial processes, performance and
      output indicators. In the absence of an effective consumer voice, the impetus for
      change has come from the Ministry of Public Health, which has supported the
      development of an accreditation programme for hospitals. This paper describes and
      analyses the experience of Lebanon in introducing this programme. It looks at the
      application of normative measures on private institutions that have been used to
      operating in a loosely controlled environment with little accountability.

PMID- 17546917
TI  - Psychological aspects of orthognathic surgery and its effect on quality of life
      in Egyptian patients.
AB  - A study was made of 120 patients aged 11-33 years who underwent various types of
      orthognathic surgery in a Cairo hospital between 1998 and 2004. Patients answered
      a standardized questionnaire to identify motives for seeking surgery, the degree
      of satisfaction with the outcome and its effect on quality of life.
      Preoperatively, aesthetic reasons were the primary motive for seeking surgery in
      95% of patients. Postoperatively, 85% of the patients were positive about the
      outcome of surgery as well as its effect on their quality of life. Postoperative
      improvement of facial aesthetics of the patients was associated with improvement
      of their quality of life in all aspects tested.

PMID- 17546918
TI  - Internists in training; what do they know about inhalers?
AB  - The study tested the knowledge of internal medicine residents in recognizing the
      types and demonstrating the ways of using 6 different inhalers. Of the residents
      61%, 49%, 78% and 90% were unable to recognize commonly used devices (a metered
      dose inhaler, Turbuhaler, Diskus and Diskhaler respectively), while 24%, 53%, 81%
      and 93% were unable to demonstrate the correct the ways of using them. None of
      the residents (0%) were able to recognize or to demonstrate the use of Rotahaler
      and Aerolizer correctly. None of them had received any formal education about the
      use of the inhalers during their training, while only 2% had attended sessions
      with medical educators.

PMID- 17546919
TI  - Profile of diabetes health care at Benghazi Diabetes Centre, Libyan Arab
      Jamahiriya.
AB  - The aim of this study was to assess the standards of care and patients' knowledge
      and practices at Benghazi Diabetes Centre, the largest diabetes registry in the
      Libyan Arab Jamahiriya. A sample of 805 attending patients was interviewed over 2
      months in 2002. Overall, 48.3% had never had blood pressure checked and 14.2% had
      never had a fundus examination and none had ever had glycosylated haemoglobin
      estimation. Only 2.4% of type 1 diabetics used a glucometer and 8.0% of all
      diabetics used urine sticks. Many patients were not compliant with treatment and
      were ignorant about hypoglycaemia symptoms or the complications of diabetes.
      Better continuing care and better education is needed for diabetic patients in
      this clinic.

PMID- 17546920
TI  - Developing a culturally valid and reliable quality of life questionnaire for
      diabetes mellitus.
AB  - The aim of this study was to design a culturally adapted questionnaire for
      studying quality of life (QOL) among type 1 and 2 adult diabetes patients in the
      Islamic Republic of Iran. The 41 items on the questionnaire were based on
      qualitative research and covered general and health-related QOL. In a descriptive
      survey, 104 patients completed the questionnaire; 68 (65.4%) were female. Mean
      age was 50.5 years (standard deviation 12.8). Most patients (86.5%) had type 2
      diabetes. Cronbach's alpha coefficient for the questionnaire was 0.98. The
      questionnaire successfully distinguished the lower QOL of patients suffering from
      pain in the limbs, loss of appetite, fatigue, constipation and itching. The
      questionnaire could determine both general and health-related QOL.

PMID- 17546921
TI  - Community participation in environmental health: Eastern Azerbaijan Healthy
      Villages project.
AB  - The objective of this project in East Azerbaijan villages was to improve
      community participation in rural areas in a Healthy Villages programme. The
      project covered 1680 villages, and 3605 training courses for health staff and
      village residents on environmental health were conducted in 10 stages from 1992
      to 2000. Men's and women's health councils in villages were established in 92%
      and 62% of villages respectively. In 39% of villages, people collected animal
      waste and improved the disposal collection process. A decrease in the prevalence
      of parasitic disease in the area was prominent after the project.

PMID- 17546922
TI  - Opinions of an Iranian nursing faculty on barriers to implementing problem-based
      learning.
AB  - We investigated the opinions of all 53 lecturers in the nursing faculty of Tabriz
      University of Medical Sciences about barriers to implementation of problem-based
      learning (PBL). A 13-item questionnaire was used which included questions on
      number and preparedness of students and lecturers, educational space and course
      content. We found that 95% of the respondents believed that the most important
      barrier was the students' lack of knowledge and skills in group work and active
      interaction; 94% also believed that the change in their role from lecturer to
      facilitator would not reduce their motivation but it could be a potential
      barrier. The majority (98%) indicated that the cost of implementation and
      maintenance of PBL, too many students and a shortage of lecturers competent in
      PBL were among the barriers that needed to be considered.

PMID- 17546923
TI  - Comparison of fern and evaporation tests for detection of ruptured fetal
      membranes.
AB  - Timely diagnosis of ruptured fetal membranes during the pregnancy is important.
      This study in the Islamic Republic of Iran compared the sensitivity and
      specificity of the evaporation test that requires no special equipment with the
      standard fern test requiring a microscope. Two groups of 50 pregnant women were
      studied: 1 with artificially ruptured membranes (gold standard) and 1 with intact
      membranes. The positive and negative predictive values of the fern test were 92%
      and 96% and for the evaporation test were 89% and 98%. The evaporation test is a
      simple, easy and non-expensive diagnostic test for ruptured membranes.

PMID- 17546924
TI  - Genetic pattern of 3 cases of Emery-Dreifuss muscular dystrophy in a family.

PMID- 17546925
TI  - Chlorine residual efficiency in inactivating bacteria from secondary
      contamination.

PMID- 17546926
TI  - Health impact of the Israeli invasion on Nablus.

PMID- 17546927
TI  - Evaluation of needle-stick injuries among health care workers in Isfahan
      province, Islamic Republic of Iran.

PMID- 17546928
TI  - Taking patients' values seriously.

PMID- 17546929
TI  - How much risk can medicine allow a willing altruist?

PMID- 17546930
TI  - Living donor transplantation: the perfect balance of public oversight and medical
      responsibility.

PMID- 17546931
TI  - What should we do with patients who buy a kidney overseas?

PMID- 17546932
TI  - As sure as eggs? Responses to an ethical question posed by Abramov, Elchalal, and
      Schenker.

PMID- 17546933
TI  - Is subfertility a medical condition?

PMID- 17546935
TI  - Ethical considerations in clinical care of the "VIP".

PMID- 17546936
TI  - Ethics consultants' recommendations for life-prolonging treatment of patients in
      persistent vegetative state: a follow-up study.

PMID- 17546937
TI  - Embracing the new world of personalized medicine.

PMID- 17546938
TI  - A rare ulcer with a common cause.

PMID- 17546939
TI  - Atrial fibrillation: more help for the most common arrhythmia.

PMID- 17546940
TI  - Guidelines for treatment of sport-related concussions.

PMID- 17546941
TI  - An unusual cause of pancreatitis in a young man.

PMID- 17546942
TI  - Can cellular cardiomyoplasty cure heart failure?

PMID- 17546944
TI  - TMI (too much information).

PMID- 17546943
TI  - Reviewing prognostic factors in breast cancer management.

PMID- 17546945
TI  - Can B vitamin therapy help to prevent future vascular events?

PMID- 17546946
TI  - Should I get the HPV vaccine?

PMID- 17546947
TI  - A young man with acute onset of testicular pain.

PMID- 17546948
TI  - Case of the month. Ruptured aneurysm of the ulnar artery.

PMID- 17546949
TI  - Aquaporins of tonoplast and plasmalemma in axial organs of germinating broad bean
      seeds.

PMID- 17546950
TI  - Simulation of growth of colonies of filamentous fungi in a hydrogen peroxide
      gradient.

PMID- 17546951
TI  - Guanosine and inosine (riboxin) eliminate the long-lived protein radicals induced
      X-ray radiation.

PMID- 17546952
TI  - Orange-red light attenuates inhibition of proliferation of rat fibroblasts
      induced by ultraviolet-A.

PMID- 17546953
TI  - Mycoplasma adaptation to adverse growth conditions: nanotransformation and
      phytopathogenicity of Acholeplasma laidlawii PG8.

PMID- 17546954
TI  - Substrate specificity of catalytic autoantibodies in neurodegenerative processes.

PMID- 17546955
TI  - CombiHIVvac vaccine which contains polyepitope B and T- cell immunogens of HIV-1.

PMID- 17546956
TI  - Aggregation and physiological effect on plant cells of amphiphilic
      calix[4]resorcinarenes with hydroxymethylmethylamide and carboxymethyl groups.

PMID- 17546957
TI  - Changes in the shape of photodynamically damaged Tetrahymena pyriformis cells.

PMID- 17546958
TI  - Retrotransposon gtwin in the Drosophila melanogaster laboratory strain G-32: an
      increased number of copies of this element in the genome caused chromosomal
      aberration.

PMID- 17546959
TI  - Effect of dimeric derivatives of netropsin and their combinations with acyclovir
      on herpes simplex virus type 1 infection in mice.

PMID- 17546960
TI  - A new marker of tamoxifen resistance of estrogen receptor-positive breast cancer.

PMID- 17546961
TI  - Activation of growth and accumulation of phenolic compounds in tea callus culture
      by melafen is not associated with its possible cytokinin activity.

PMID- 17546962
TI  - Changes in the structure of collagen in the annulus fibrosus under thermal or IR
      laser treatment.

PMID- 17546963
TI  - Where are we with biofilms now? Where are we going?
AB  - The IWA's BiofilmVl conference presented a wide range of research on biofilm
      systems. Particularly popular themes were nitrogen removal, mathematical
      modelling and microbial ecology. Emerging themes included biofilms with
      membranes, pathogens in biofilms, biofouling and detachment. Within microbial
      ecology and mathematical modelling, emphasis was given to N-removal systems,
      particularly involving nitrifiers and Anammox bacteria. Both themes also
      recognised the importance of biofilm detachment. Although biofilms on membranes
      gained attention, little interest was exhibited towards linking biofilms with
      other advanced materials, such as ceramics, conductors, semi-conductors or nano
      materials. Research presented at BiofilmVI marked major advances in improving
      water sustainability towards removing BOD and N, but did not address many
      emerging contaminants, such as oxidised contaminants and endocrine disruptors.
      Attention to energy sustainability, such as with bio-hydrogen or microbial fuel
      cells, was minimal. Thus, research reported at BiofilmVI was strong towards
      "improving the expected" with regard to BOD and N removal, but not yet focused on
      "exploiting the unexpected" to deal with emerging pollutants and bio-energy.

PMID- 17546964
TI  - Development of a super high-rate Anammox reactor and in situ analysis of biofilm
      structure and function.
AB  - The anaerobic ammonium oxidation (Anammox) process is a new efficient and cost
      effective method of ammonium removal from wastewater. Under strictly anoxic
      condition, ammonium is directly oxidised with nitrite as electron acceptor to
      dinitrogen gas. However, it is extremely difficult to cultivate Anammox bacteria
      due to their low growth rate. This suggests that a rapid and efficient start-up
      of Anammox process is the key to practical applications. To screen appropriate
      seeding sludge with high Anammox potential, a real-time quantitative PCR assay
      with newly designed primers has been developed. Thereafter, the seeding sludge
      with high abundance of Anammox bacteria (1.7 x 10(8) copies/mg-dry weight) was
      selected and inoculated into an upflow anaerobic biofilters (UABs). The UABs were
      operated for more than 1 year and the highest nitrogen removal rate of 24.0 kg-N
      m-3 day(-1) was attained. In addition, the ecophysiology of Anammox bacteria
      (spatial distribution and in situ activity) in biofilms was analysed by combining
      a full-cycle 16S rRNA approach and microelectrodes. The microelectrode
      measurement clearly revealed that a successive vertical zonation of the partial
      nitrification (NH4+ to NO2-), Anammox reaction and denitrification was developed
      in the biofilm in the UAB. This result agreed with the spatial distribution of
      corresponding bacterial populations in the biofilm. We linked the micro-scale
      information (i.e. single cell and/or biofilm levels) with the macro-scale
      information (i.e. the reactor level) to understand the details of Anammox
      reaction occurring in the UABs.

PMID- 17546965
TI  - A one-stage system with partial nitritation and anammox processes in the moving
      bed biofilm reactor.
AB  - The ability of bacterial cultures to create biofilm brings a possibility to
      enhance biological wastewater treatment efficiency. Moreover, the ability of
      Anammox and Nitrosomonas species to grow within the same biofilm layer enabled a
      one-stage system for nitrogen removal to be designed. Such a system, with Kaldnes
      rings as carriers for biofilm growth, was tested in a technical pilot plant scale
      (2.1 m(3)) at the Himmerfjarden Waste Water Treatment Plant (WWTP) in the
      Stockholm region. The system was directly supplied with supernatant originating
      from dewatering of digested sludge containing high ammonium concentrations.
      Nearly 1-year of operational data showed that during the partial
      nitritation/Anammox process, alkalinity was utilised parallel to ammonium
      removal. The process resulted in a small pH drop, and its relationship with
      conductivity was found. The nitrogen removal rate for the whole period oscillated
      around 1.5g N m(-2)d(-1) with a maximum value equal to 1.9 g N m(-2)d(-1).
      Parallel to the pilot plant experiment, a series of batch tests were run to
      investigate the influence on removal rates of different dissolved oxygen
      conditions and addition of nitrite. The highest nitrogen removal rate (5.2g N m(
      2)2d(-1)) in batch tests was obtained when the Anammox process was stimulated by
      the addition of nitrite. In the simultaneous partial nitritation and Anammox
      process, the partial nitritation was the rate-limiting step.

PMID- 17546966
TI  - Full-scale granular sludge Anammox process.
AB  - The start-up of the first full scale Anammox reactor is complete. The reactor
      shows stable operation, even at loading rates of 10 kg N/m3.d. This performance
      is the result of the formation of Anammox granules, which have a high density and
      settling velocities exceeding 100 m/h. With this performance, the Anammox
      granular sludge technology has been proven on full scale.

PMID- 17546967
TI  - Biological nitrogen removal from landfill leachate by deammonification assisted
      by heterotrophic denitrification in a rotating biological contactor (RBC).
AB  - Due to negative environmental effects of nitrogen discharge to recipients and
      increasingly stringent effluent standards, effective nitrogen removal is
      necessity. Biological methods are the simplest and cheapest way to treat
      wastewater; however, it may become an extremely expensive option when high
      influent nitrogen concentrations are measured and there is a lack of
      biodegradable organic carbon. Therefore, there is a great need to find new
      solutions and improve existing technologies. The deammonification is an excellent
      example of such a new process that requires considerably low amounts of organic
      carbon and oxygen in comparison to conventional nitrification/denitrification.
      The main objective of presented research was to investigate an Anammox process
      accompanied with autotrophic nitrification and heterotrophic denitrification in
      one rotating biological contactor (RBC). During the research period, it was
      possible to carry out the Anammox process in low temperature below 20 'C.
      Additionally, it was found that the process is insensitive to high nitrite
      concentration in the reactor, up to 100 g NO2-N m(-3), resulting only in a
      temporary decrease in removal rates. Furthermore, analysis of data indicated that
      the Stover-Kincannon model can be used for the description of ammonium and
      nitrite removal processes.

PMID- 17546968
TI  - Evaluation of hybrid processes for nitrification by comparing MBBR/AS and IFAS
      configurations.
AB  - An integrated fixed-film activated sludge (IFAS) pilot plant and a moving bed
      biofilm reactor coupled with an activated sludge process (MBBR/AS) were operated
      under different temperatures, carbon loadings and solids retention times (SRTs).
      These two types of hybrid systems were compared, focusing on the nitrification
      capacity and the nitrifiers population of the media and suspended biomass
      alongside other process performances such as carbonaceous and total nitrogen (TN)
      removal rates. At high temperatures and loadings rates, both processes were fully
      nitrifying and achieved similarly high carbonaceous removal rates. However, under
      these conditions, the IFAS configuration performed better in terms of TN removal.
      Lower temperatures and carbon loadings led to lower carbonaceous removal rates
      for the MBBR/AS configuration, whereas the IFAS configuration was not affected.
      However, the nitrification capacity of the IFAS process decreased significantly
      under these conditions and the MBBR/AS process was more robust in terms of
      nitrification. Ammonia oxidising bacteria (AOB) and nitrite oxidising bacteria
      (NOB) population counts accurately reflected the changes in nitrification
      capacity. However, significantly less NOBs than AOBs were observed, without
      noticeable nitrite accumulation, suggesting that the characterisation method used
      was not as sensitive for NOBs and/or that the NOBs had a higher activity than the
      AOBs.

PMID- 17546969
TI  - Nutrients removal in hybrid fluidised bed bioreactors operated with aeration
      cycles.
AB  - Abstract Two hybrid fluidised bed reactors filled with sepiolite and granular
      activated carbon (GAC) were operated with short cycled aeration for removing
      organic matter, total nitrogen and phosphorous, respectively. Both reactors were
      continuously operated with synthetic and/or industrial wastewater containing 350
      500 mg COD/L, 110-130 mg NKT/L, 90-100 mg NH3-N/L and 12-15 mg P/L for 8 months.
      The reactor filled with sepiolite, treating only synthetic wastewater, removed
      COD, ammonia, total nitrogen and phosphorous up to 88, 91, 55 and 80% with a
      hydraulic retention time (HRT) of 10 h, respectively. These efficiencies
      correspond to removal rates of 0.95 kgCODm(-3)d(-1) and 0.16 kg total N m(-3)d(
      1). The reactor filled with GAC was operated for 4 months with synthetic
      wastewater and 4 months with industrial wastewater, removing 98% of COD, 96% of
      ammonia, and 66% of total nitrogen, with an HRT of 13.6 h. No significant
      phosphorous removing activity was observed in this reactor. Microbial communities
      growing with both reactors were followed using polymerase chain reaction (PCR)
      and denaturing gradient gel electrophoresis (DGGE) techniques. The microbial
      fingerprints, i.e. DGGE profiles, indicated that biological communities in both
      reactors were stable along the operational period even when the operating
      conditions were changed.

PMID- 17546970
TI  - Total nitrogen removal from high-strength ammonia recycle stream using a single
      submerged attached growth bioreactor.
AB  - An experimental study investigating the nitrogen removal efficiency from the
      recycle stream generated in the dewatering facility of the anaerobically digested
      sludge at the Deer Island wastewater treatment plant (WWTP) in Boston was
      conducted using a single submerged attached growth bioreactor (SAGB), designed
      for simultaneous nitrification and denitrification. The applied nitrogen loading
      to the reactor ranged from 0.7 to 2.27 kg-N/m3xd, and the corresponding total
      nitrogen (TN) removal rate ranged from 0.38 to 1.8 kg-N/m(3)xd. The observed
      nitrification rates varied from 0.42 kg-N/m3-d to 1.45 kg-N/m(3) xd with an
      ammonia load of 0.5 kg-N/m3-d and 1.8 kg-N/m(3)xd, respectively. An average
      nitrification efficiency of 91% was achieved throughout the experiment.
      Denitrification efficiency varied from 55%/o, obtained without any addition of
      carbon source, to 95% when methanol was added in order to obtain a
      methanol/nitrate ratio of about 3 kg methanol/kg NO3- -N.

PMID- 17546971
TI  - Inhibitory effect of the xenobiotic 1,2-dichloroethane in a nitrifying biofilm
      reactor.
AB  - The aim was to investigate the inhibitory effect of the xenobiotic 1,2-DCA on
      nitrification during the cometabolic degradation in a packed bed nitrifying
      biofilm reactor. This xenobiotic inhibited primarily the conversion of NH4-N to
      hydroxylamine by binding to the AMO enzyme. It had no inhibitory effect on the
      conversion of nitrite to nitrate. At high NH4-N loadings, the presence of 1,2-DCA
      inhibited NH4-N utilisation more severely than at low loadings. The suppressing
      effect of 1,2-DCA on NH4-N utilisation was found to be reversible due to the
      ability of cells to recover from inhibition. These results could fill a gap in
      the literature about the potential use of nitrifying biofilm systems for
      cometabolic treatment of 1,2-DCA and could be useful in the design of engineered
      1,2-DCA remediation/treatment in biofilm reactors.

PMID- 17546972
TI  - Aerobic granular sludge--state of the art.
AB  - In September 2006, preliminary to the IWA biofilm conference, a second workshop
      about aerobic granular sludge was held in Delft, The Netherlands, of which a
      summary of the discussion outcomes is given in this paper. The definition of
      aerobic granular sludge was discussed and complemented with a few additional
      demands. Further topics were formation and morphology of aerobic granular sludge,
      modelling and use of the aerobic granular sludge in practice.

PMID- 17546973
TI  - Wastewater treatment with submerged fixed bed biofilm reactor systems--design
      rules, operating experiences and ongoing developments.
AB  - Wastewater treatment systems using bio-films that grow attached to a support
      media are an alternative to the widely used suspended growth activated sludge
      process. Different fixed growth biofilm reactors are commercially used for the
      treatment of municipal as well as industrial wastewater. In this paper a fairly
      new fixed growth biofilm system, the submerged fixed bed biofilm reactor (SFBBR),
      is discussed. SFBBRs are based on aerated submerged fixed open structured plastic
      media for the support of the biofilm. They are generally operated without sludge
      recirculation in order to avoid clogging of the support media and problems with
      the control of the biofilm. Reactor and process design considerations for these
      reactors are reviewed. Measures to ensure the development and maintenance of an
      active biofilm are examined. SFBBRs have been applied successfully to small
      wastewater treatment plants where complete nitrification but no high degree of
      denitrification is necessary. For the pre-treatment of industrial wastewater the
      use of SFBBRs is advantageous, especially in cases of wastewater with high
      organic loading or high content of compounds with low biodegradability.
      Performance data from exemplary commercial plants are given. Ongoing research and
      development efforts aim at achieving a high simultaneous total nitrogen (TN)
      removal of aerated SFBBRs and at improving the efficiency of TN removal in anoxic
      SFBBRs.

PMID- 17546974
TI  - Benchmarking of BAF plants: operational experience on 40 full-scale installations
      in Germany.
AB  - For some years, bio-filtration has been used in municipal wastewater treatment as
      a relatively new method. Within a German DWA research project, the method of
      benchmarking was used to compile and scientifically evaluate performance data and
      operation experiences with this technology on municipal wastewater treatment
      plants in Germany. This report presents selected partial results from the
      project. Generally, it becomes apparent that bio-filters as supplementary
      technology allow for additional improvements in regard to the COD and nitrogen
      effluent values. Bio-filtration is a compact method which combines biological
      purification processes with the filtration process. Apart from sound results in
      regard to the operation costs, operational problems (MSR technology, filter
      material losses) are described. In terms of energy balances, dimensions of the
      biological main stages can be compared to other biological purification methods.
      In regard to the sludge production, further research is necessary.

PMID- 17546975
TI  - Comparing cost and process performance of activated sludge (AS) and biological
      aerated filters (BAF) over ten years of full sale operation.
AB  - In the early 1990s, the Wastewater Treatment Plant (WWTP) of Frederikshavn,
      Denmark, was extended to meet new requirements for nutrient removal (8 mg/L TN,
      1.5 mg TP/L) as well as to increase its average daily flow to 16,500 m(3)/d (4.5
      MGD). As the most economical upgrade of the existing activated sludge (AS) plant,
      a parallel biological aerated filter (BAF) was selected, and started up in 1995.
      Running two full scale processes in parallel for over ten years on the same
      wastewater and treatment objectives enabled a direct comparison in relation to
      operating performance, costs and experience. Common pretreatment consists of
      screening, an aerated grit and grease removal and three primary settlers with
      chemical addition. The effluent is then pumped to the two parallel biological
      treatment stages, AS with recirculation and an upflow BAF with floating media.
      The wastewater is a mixture of industrial and domestic wastewater, with a
      dominant discharge of fish processing effluent which can amount to 50% of the
      flow. The maximum hydraulic load on the pretreatment section as a whole is 1,530
      m(3)/h. Approximately 60% of the sewer system is combined with a total of 32
      overflow structures. To avoid the direct discharge of combined sewer overflows
      into the receiving waters, the total hydraulic wet weather capacity of the plant
      is increased to 4,330 m(3)/h, or 6 times average flow. During rain, some of the
      raw sewage can be directed through a stormwater bypass to the BAF, which can be
      modified in its operation to accommodate various treatment needs: either using
      simultaneous nitrification/denitrification in all filters with recirculation
      introducing bottom aeration with full nitrification in some filters for storm
      treatment and/or post-denitrification in one filter. After treatment, the
      wastewater is discharged to the Baltic Sea through a 500 m outfall. The BAF
      backwash sludge, approximately 1,900 m(3) per 24 h in dry weather, is redirected
      to the AS plant. Primary settler sludge and the combined biosolids from the AS
      plant are anaerobically digested, with methane gas being used for generation of
      heat and power. On-line measurements for the parameters NO3, NO2, NH4,
      temperature as well as dissolved oxygen (DO) are used for control of aeration and
      external carbon source (methanol). Dosing of flocculants for P-removal is carried
      out based on laboratory analysis and jar tests. This paper discusses the
      experience gained from the plant operation during the last ten years, compiling
      comparative performance and cost data of the two processes, as well as their
      optimisation.

PMID- 17546976
TI  - Full-scale applications for both COD and nutrient removal in a CIRCOX airlift
      reactor.
AB  - The airlift reactor technology has been successfully applied at full scale for
      both COD and nitrogen removal. In this study, the results of the biofilm
      development and biological performance of two full scale reactors are discussed.
      At Paulaner Brewery in Munich, the airlift reactor was applied for COD and
      ammonia removal of anaerobically treated wastewater. In the other case the
      airlift reactor was applied as a pretreatment of nitrogen removal by the Anammox
      process. Water from a Tannery company in Lichtenvoorde in the Netherlands, The
      Hulshof Royal Dutch Tanneries, was pretreated anaerobically for COD removal and
      aerobically to remove the sulphides as sulphur. In an airlift reactor the ammonia
      was partially oxidised to nitrite. In both cases the granular biomass developed
      well; the concentrations amounted to 250 microl/L and 500 ml/L respectively. In
      the first case, 4 kg/m(3)/day of COD was removed, the soluble concentration of
      COD was less than 250 mg/L. The nitrification to nitrate was nearly complete and
      amounted to 0.5 kg NH4-N/m(3)/day. In the second application, 50% of the ammonia
      (on average 0.45 kg N/m3/d) was nitrified to nitrite. This process was easily
      controlled by regulating the amount of air according to the nitrite and ammonia
      concentrations in the effluent. It can be concluded that in both cases the
      particular processes were very stable and easy to operate.

PMID- 17546977
TI  - Potentials and limits of a pre-denitrification/ nitrification biofilter
      configuration for advanced municipal wastewater treatment.
AB  - Pre-denitrification in biofilters is limited by the amount of easily degradable
      organic substrate, resulting in relatively high requirements for external carbon.
      The combination of pre-DN, N and post-DN filters is much more advisable for most
      municipal wastewaters, because the recycle rate can be reduced and external
      carbon can be saved. For minimum use of external carbon, 100-150% recycle rate
      should not be exceeded. Then, approximately 50-60% of the total NO3-N can be
      depleted in the pre-DN stage. On average, 10 g total (t) COD/g NO3-N were
      required in the pre-DN stage for denitrification in the pilot and full-scale
      plant and 0.4-0.5 kg NO3-N/(m(3)DN d) can be reached without external carbon. As
      only 40-70% of the COD load is eliminated in the pre-DN, the remaining COD load
      is removed in the nitrification stage. 1 kg COD/(m(3) d) suppresses nitrification
      rates by approximately 0.1 kg NH4-N/(m(3) d). For nitrification rates, > 0.5 kg
      NH4N/(m(3) d) at 12 degrees C not more than 2 kg COD/(m(3) d) may be eliminated
      in the nitrification.

PMID- 17546978
TI  - Performances of a granular sequencing batch reactor (GSBR).
AB  - Aerobic granulation in sequencing batch reactors is widely reported in literature
      and in particular in SBAR (Sequencing batch airlift reactor) configuration, due
      to the high localised hydrodynamic shear forces that occur in this type of
      configuration. The aim of this work was to observe the phenomenon of the aerobic
      granulation and to confirm the excellent removal efficiencies that can be
      achieved with this technology. In order to do that, a laboratory-scale plant,
      inoculated with activated sludge collected from a conventional WWTP, was operated
      for 64 days: 42 days as a SBAR and 22 days as a SBBC (sequencing batch bubble
      column). The performances of the pilot plant showed excellent organics removal.
      COD and BOD removal efficiencies were respectively, 93 and 94%; on the contrary,
      N-removal efficiency was extremely low (5%-45%/o). The granules dimensions
      increased during the whole experimentation; change of reactor configuration
      contributed to further improve this aspect. The experimental work confirmed the
      essential role of hydraulic settling time in the formation of aerobic granules
      and in the sludge settleability and the need to find an optimum between granule
      size and oxygen supply to achieve good N-removal efficiency.

PMID- 17546979
TI  - A pilot-plant study of a moving-bed biofilm reactor system using PVA gel as a
      biocarrier for removals of organic carbon and nitrogen.
AB  - A pilot-plant study was conducted to evaluate the performance of a moving-bed
      biofilm reactor process using PVA-gel beads as a biocarrier. Real primary-settled
      wastewater was fed to the pre-denitrification system and removals of nitrogenous
      and organic contaminants were evaluated over a 1-year period. The results
      demonstrated that at a total nitrogen (TN) loading of 18 mg/L.h, a TN removal
      efficiency in keeping with and even exceeding the theoretical maximum efficiency
      based on the level of internal recycle, was possible and a nitrification rate of
      15 mg/L.h was sustained with a HRT of only 2.5 h at 15 degrees C. Furthermore,
      soluble COD and BOD5 in the effluent of the pilot plant were reduced to levels
      well below most regulatory discharge limits. In addition, the possibility of
      using this biocarrier in a system, including the elimination of waste organic
      sludge, was discussed.

PMID- 17546980
TI  - Iron and manganese removal from textile effluents in anaerobic attached-growth
      bioreactor filled with coirfibres.
AB  - A laboratory scale study on Fe and Mn removal in upflow anaerobic bioreactor of a
      working volume of 20 L with coir fibre as the filter medium was investigated for
      a period of 312 days. The maximum Fe and Mn levels considered were 10 and 5 mg/L
      respectively, which are the typical average values of textile effluents
      subsequent to the primary and secondary treatments. Ten sub-experimental runs
      were conducted with varying HRTs (5 days to 1 day), ratios of COD:SO42- (20 to
      3.5), Fe levels (0.005 to 10 mg/L) and Mn levels (0 to 5 mg/L). COD:SO2 of 3.5
      was identified as the optimum point at which sulphate reducing bacteria (SRBs)
      out competed methane producing bacteria (MPBs) and further reduction of this
      ratio caused total and/or significant inhibition of MPBs, thus building sulphate
      reducing conditions. The effluent contained Fe and Mn below the permissible
      levels (1.6 and 1.1 mg/L for Fe and Mn, respectively) stipulated by US National
      Pollution Discharge Elimination System (NPDES) for inland surface waters at HRTs
      higher than 3 days. Results of the mass balance showed more Fe accumulation (60%)
      in sediments whereas 27% in the filter media. An opposite observation was noticed
      for Mn.

PMID- 17546981
TI  - Sequencing batch reactor (SBR) as optimal method for production of granular
      activated sludge (GAS)--fluid dynamic investigations.
AB  - Fluid dynamic investigations of multiphase flow (fluid, air, granules) in a
      sequencing batch reactor (SBR) are presented. SBR can be considered as an
      attractive technology for cultivation of granular activated sludge (GAS).
      Granulation is a complicated process and its mechanism is not fully understood
      yet. Many factors influence the formation and structure of aerobic granular
      sludge in a bioreactor. Extracellular polymer substances (EPS) and superficial
      gas velocity (SGV) play a crucial role for granules formation. Additionally, it
      is supposed that EPS production is stimulated by mechanical forces. It is also
      assumed that hydrodynamic effects have a major influence on the formation, shape
      and size of GAS in SBR under aerobic condition. However, the influence of stress
      on granulation is poorly investigated. Thus, in the present paper, fluid dynamic
      investigations of multiphase flow in a SBR, particularly effect of normal and
      shear strain, are reported. In order to analyse multiphase flow in the SBR,
      optical in-situ techniques with particle image velocimetry (PIV) and particle
      tracking velocimetry (PTV) are implemented. Obtained results show a
      characteristic flow pattern in a SBR. It is pointed out that additional effects
      like particle-wall collisions, inter particle collisions, erosion can also affect
      significantly granules formation.

PMID- 17546982
TI  - Effect of temperature and salinity on the wastewater treatment performance of
      aerobic submerged fixed bed biofilm reactors.
AB  - The influence of temperature (5-35 C) and salinity (up to 20 g/l NaCl) on the
      wastewater purification process in completely mixed and aerated submerged fixed
      bed biofilm reactors (SFBBRs) was studied. C- and N-conversion in SFBBRs designed
      according to the DWA (German Association for Water, Wastewater and Waste) rules
      for carbon removal was investigated for several months on synthetic wastewater.
      The DOC degradation rate was even at, according to the DWA, high DOC/BOD loading
      rates not much affected by temperatures between 5-35 degrees C and salt contents
      up to 20 g/L NaCl. At these high DOC loadings an appreciable ammonium conversion
      could also be observed. The ammonium conversion proved to be sensitive to
      temperature and salinity. At 5 degrees C the ammonium removal rate decreased by a
      factor of five compared to 25-35 degrees C. Under many operation conditions
      investigated more than 50% of the converted ammonium was transformed into gaseous
      nitrogen. The addition of 20 g/L NaCl caused a strong inhibition of the ammonium
      removal rate over the whole temperature range investigated.

PMID- 17546983
TI  - Influence of temperature on microbial colonisation of clayey schist as a support
      media of a submerged filter for groundwater denitrification.
AB  - The effect of temperature on biofilm formation and denitrification activity was
      evaluated. Assays were made in a lab-scale submerged filter for the
      denitrification of polluted groundwater, with and without a previous inoculation.
      The inoculation was carried out with a selected strain of Pseudomonas mandelii.
      Different temperatures were tested: 5, 10, 20 and 30 degrees C. Biofilm
      observations were made, and monitoring of the denitrification capacity of the
      system was maintained during the experiment. Our results showed that both
      colonisation of the support material of the filter and biofilm maturity have a
      dependency with temperature, with an optimum temperature of 20 'C if the system
      was previously inoculated with the Pseudomonas mandelii strain. For a correct
      achievement of the denitrification process, a previous inoculation of the system
      is essential. Although the development of a biofilm from the natural microbiota
      present in the groundwater is possible, it is not capable to adequately denitrify
      polluted groundwater. In terms of the correct achievement of the denitrification
      process, temperature affects the operation of the system at cold environments,
      although the use of Pseudomonas mandelii strain A103 allows denitrification at 10
      30 degrees C with very good results (above 90% removal), affecting only to the
      time needed for the stabilisation of the system.

PMID- 17546984
TI  - Influence of backwashing on the microbial community in a biofilm developed on
      biological activated carbon used in a drinking water treatment plant.
AB  - The influence of backwashing on the biofilm community developed on biological
      activated carbon (BAC) used in a drinking water treatment plant was investigated
      by means of bacterial cell enumeration and terminal-restriction fragment length
      polymorphism (T-RFLP) fingerprinting analysis of bacterial and eukaryotic
      ribosomal RNA genes (rDNA). After backwashing, the attached bacterial abundance
      in the top layer of the BAC bed decreased to 64% of that before backwashing. The
      community level changes caused by backwashing were examined through the T-RFLP
      profiles. In the bacterial 16S rDNA analysis, the relative abundances of some
      terminal-restriction fragments (T-RFs) including the Planctomycetes-derived
      fragment increased; however, the relative abundances of some T-RFs including the
      Betaproteobacteria-derived fragments decreased. In the eukaryotic 18S rDNA
      analysis, the relative abundances of some T-RFs including the protozoan Cercozoa
      derived fragments increased; however, the relative abundances of some T-RFs
      including the metazoan Chaetonotus- and Paratripyla-derived fragments decreased.
      The T-RFLP analysis suggests that backwashing can cause changes in the relative
      compositions of microorganisms in a BAC biofilm in the top layer of the bed.

PMID- 17546985
TI  - Investigation of microbial communities on reverse osmosis membranes used for
      process water production.
AB  - In the present study, the diversity and the phylogenetic affiliation of bacteria
      in a biofouling layer on reverse osmosis (RO) membranes were determined. Fresh
      surface water was used as a feed in a membrane-based water purification process.
      Total DNA was extracted from attached cells from feed spacer, RO membrane and
      product spacer. Universal primers were used to amplify the bacterial 16S rRNA
      genes. The biofilm community was analysed by 16S rRNA-gene-targeted denaturing
      gradient gel electrophoresis (DGGE) and the phylogenetic affiliation was
      determined by sequence analyses of individual 16S rDNA clones. Using this
      approach, we found that five distinct bacterial genotypes (Sphingomonas, Beta
      proteobacterium, Flavobacterium, Nitrosomonas and Sphingobacterium) were dominant
      genera on surfaces of fouled RO membranes. Moreover, the finding that all five
      "key players" could be recovered from the cartridge filters of this RO system,
      which cartridge filters are positioned before the RO membrane, together with
      literature information where these bacteria are normally encountered, suggests
      that these microorganisms originate from the feed water rather than from the RO
      system itself, and represent the fresh water bacteria present in the feed water,
      despite the fact that the feed water passes an ultrafiltration (UF) membrane
      (pore size approximately 40 nm), which is able to remove microorganisms to a
      large extent.

PMID- 17546986
TI  - Biofilm growth in response to various concentrations of biodegradable material in
      drinking water.
AB  - Biological stability is one of the most important aspects of safe drinking water.
      It depends crucially on the availability of biodegradable organic carbon (BDOC).
      Measurement of BDOC is time-consuming and only performed if an increase is
      suspected. In this study, a fibre optical sensor (FOS) was used to detect changes
      in BDOC, detected as an increase in biofilm growth. The FOS consists of a sending
      and a receiving optical fibre, the latter connected to a detector. When material
      is deposited at the tip of the fibre, an increase of backscattered light is
      detected. In a system fed with drinking water, the signal was correlated to
      biofilm growth which was confirmed by independent surface colonisation
      determination. When 1 and 3mgL(-1) of BDOC respectively was added, the increment
      of the FOS signal over a period of 1 week could be distinguished. Interference by
      planktonic components and humic substances could be excluded. The biofilm on the
      FOS could be used as a means to detect changes in BDOC in drinking water and the
      signal has an early warning capacity.

PMID- 17546987
TI  - The membrane fouling simulator: a suitable tool for prediction and
      characterisation of membrane fouling.
AB  - A new tool--the Membrane Fouling Simulator (MFS)--is developed to measure
      membrane fouling (pressure drop increase) in a small and simple system,
      representative for spiral wound membranes applied in water treatment. With the
      MFS, fouling development can be monitored systematically by (i) pressure drop,
      (ii) in situ and non-destructive (visual) observations using the sight glass and
      (iii) analysis of coupons sampled from the membrane sheet in the MFS. A
      comparison study of the MFS with spiral wound membrane elements (test rigs and a
      full scale installation) showed the same fouling. The MFS provided reproducible
      data. The small size and low water and chemical use of the MFS facilitate to
      perform systematic parallel studies. With the MFS, fouling of membranes applied
      in water treatment can be characterised.

PMID- 17546988
TI  - Simultaneous visualisation of biofouling, organic and inorganic particle fouling
      on separation membranes.
AB  - Fouling is a major problem in membrane processes of water treatment. It can be
      caused by the deposition of inorganic and organic particulate material, and of
      microbial cells which may subsequently form biofilms. In practice, usually more
      than one foulant participates in the formation of membrane deposits. Knowledge of
      the composition of fouling layers is important for the development of appropriate
      countermeasures. For this purpose, an experimental system was established for the
      generation and microscopic visualisation of mixed deposits, using fluorescently
      labelled model foulants: (i) drinking-water bacteria stained with nucleic acid
      specific dyes (biofouling), (ii) synthetic clay mineral laponite stained with
      rhodamine 6G (inorganic particle fouling), and (iii) fluorescently labelled
      polystyrene microspheres (organic particle fouling). Polycarbonate and
      polyethersulfone membranes were challenged with these foulants by dead-end
      filtration. On the basis of different fluorescent labels, the single foulants in
      these mixed deposits could be visualised separately by confocal laser scanning
      microscopy which, in combination with image analysis, allowed the generation of
      three-dimensional views of the complete deposits. This method offers the
      possibility for the estimation of quantitative surface coverage by foulants and
      for the determination of the efficacy of cleaning measures with respect to the
      removal of different foulants.

PMID- 17546989
TI  - Evaluating the potential of biofilm control in water supply systems by removal of
      phosphorus from drinking water.
AB  - Effect of microbially available phosphorus (MAP) on biofilm development in
      drinking water systems was investigated at the pilot-scale experiments over 3
      years. Completely mixed biofilm reactors Propella (water detention time 24 h,
      flow rate 0.25 m s(-1), PVC pipe coupons) were used as water distribution network
      models. Four experimental runs were carried out with water containing different
      levels of phosphorus which was limiting nutrient for bacterial growth. Positive
      correlation between MAP in the inlet water and heterotrophic plate count
      (correlation coefficient 0.95) in biofilm, as well as for the total bacteria
      number (correlation coefficient 0.71), was observed. However, our experiments
      showed that removal of phosphorus down to very low levels (below detection limits
      of chemical method and MAP < 1 microg L(-1) was not an efficient strategy to
      eliminate bacterial regrowth and biofilm formation (< 51,00,000 cells/cm2) in
      drinking water supply systems.

PMID- 17546990
TI  - Assessing chemical cleaning of nanofiltration membranes in a drinking water
      production plant: a combination of chemical composition analysis and fluorescence
      microscopy.
AB  - The efficiency of cleaning procedures to remove the fouling deposit from the
      surface of NF membranes operating in the drinking water plant of Mery sur Oise
      (Val d'Oise, France) was assessed by a combination of chemical analysis and
      fluorescence microscopy. The ATR-FTIR spectra of the fouled membranes revealed
      the presence of biological matter at the membrane surface, mainly composed of
      polysaccharides, nucleic acids and proteins. IR bands corresponding to the
      membrane material were detected for stage 1 but not for stage 3. Confocal laser
      scanning microscopy (CLSM) observations confirmed the microbial origin of the
      fouling deposit. After chemical cleaning, the analysis of the inorganic foulants
      revealed a significant decrease of the inorganic content. Moreover, ATR-FTIR
      spectra of the fouled membranes were modified, mainly in a broad complex region
      corresponding to polysaccharides and nucleic acids. The amide bands were also
      altered for stage 1, and some peaks corresponding to the clean membrane appeared
      for stage 3 after cleaning. CLSM observations revealed a general decrease of the
      lectin staining for the two stages with some variations between lectins. A
      decrease of the DAPI staining indicative of the removal of some microbial cells
      was also observed for stage 1. In conclusion, cleaning of the NF fouled membranes
      decreased significantly the inorganic foulants but only partially removed the
      organic fouling deposit characteristic of a microbial biofilm.

PMID- 17546991
TI  - Modelling the competition of planktonic and sessile aerobic heterotrophs for
      complementary nutrients in biofilm reactor.
AB  - A comprehensive, simplified microbial biofilm model was developed to evaluate the
      impact of bioreactor operating parameters on changes in microbial population
      abundance. Biofilm simulations were conducted using three special cases: fully
      penetrated, internal mass transfer resistance and external mass transfer
      resistance. The results of model simulations showed that for certain operating
      conditions, competition for growth limiting nutrients generated oscillations in
      the abundance of planktonic and sessile microbial populations. These oscillations
      resulted in the violation of the competitive exclusion principle where the number
      of microbial populations was greater than the number of growth limiting
      nutrients. However, the operating conditions which impacted microbial community
      diversity were different for the three special cases. Comparing the results of
      model simulations for dispersed-growth, biofilms and bioflocs showed that
      oscillations and microbial community diversity were a function of competition as
      well as other key features of the ecosystem. The significance of the current
      study is that it is the first to examine competition as a mechanism for
      controlling microbial community diversity in biofilm reactors.

PMID- 17546992
TI  - Modelling of hybrid moving bed biofilm reactors: a pilot plant experiment.
AB  - In recent years there has been an increasing interest in the development of
      hybrid biofilm reactors, especially in the upgrading of existing WWTP that are no
      longer able to respect concentration limits. In fact, today's challenge is the
      achievement of a good aquatic state for the receiving water bodies according to
      the Water Framework Directive requirements, which indeed limit even more the
      continuous emissions, i.e. coming from WWTP. This paper presents the setting up
      of a mathematical model for the simulation of a hybrid MBBR system; the model
      calibration/validation has been carried out considering a field gathering
      campaign on an experimental pilot plant. The main goal is to gain insight about
      MBBR processes attempting to overcome main shortcomings in particular referring
      to the modelling aspects. The model is made up of two connected sub-models for
      the simulation of the suspended and attached biomass. The model is mainly based
      on the concepts of the activated sludge model No. 1 (ASM1) for the description of
      the biokinetic process both for the suspended and for the attached biomass. The
      results show a good agreement between predicted and observed values both for the
      attached and for the suspended biomass moreover they are encouraging for further
      researches.

PMID- 17546993
TI  - Simulation of nitrification of municipal wastewater in a Moving Bed biofilm
      process: a bottom-up approach based on a 2D-continuum model for growth and
      detachment.
AB  - This paper presents a complete mathematical model of a Moving Bed biofilm process
      for waste-water treatment, in particular for the nitrification process. The model
      is based on a bottom up approach adopting a multidimensional model for the
      biofilm growth and metabolism and a global mass balance model for the whole
      reactor. The model shows that oxygen is limiting the amount of biomass involved
      in the nitrification process. Furthermore, it suggests the existence of an
      optimal amount biomass for an optimal reactor turnover rate. Studies of two
      specific new suspended carriers show that the model output is dependable on the
      geometry of the carrier, and to a satisfactory extent agreeable with
      measurements.

PMID- 17546994
TI  - Stochastic modeling for characterisation of biofilm development with discrete
      detachment events (sloughing).
AB  - The monitoring of biofilm development at a small-scale is often observed to be a
      stochastic process. This raises important issues concerning the reproducibility
      of biofilm growth monitoring experiments. By realising that there are limits to
      the latter, a model of biofilm accumulation curves that takes into account the
      dynamics of seemingly random fluctuations resulting from sloughing events is
      proposed. The model is derived from a stochastic differential equation (SDE)
      based on the logistic equation, adding a stochastic term for the sloughing events
      and measurement noise. Experimental light absorbance data that correlate with
      biofilm biomass obtained from the development of phototrophic biofilms are
      analysed to illustrate the use of SDE modeling.

PMID- 17546995
TI  - Description of mechanical response including detachment using a novel particle
      model of biofilm/flow interaction.
AB  - Bacterial biofilms, while made up of microbial-scale objects, also function as
      meso- and macroscale materials. In particular, macro-scale material properties
      determine how biofilms respond to large-scale mechanical stresses, e.g. fluid
      shear. Viscoelastic and other constitutive properties influence biomass structure
      (through growth and fluid shear stresses) by erosion and sloughing detachment. In
      this paper, using the immersed boundary method, biofilm is modelled by a system
      of viscoelastic, breakable springs embedded in a fluid flow, evolving according
      to the basic physical laws of conservation of mass and momentum. We demonstrate
      in the context of computer simulation biofilm deformation and detachment under
      fluid shear stress.

PMID- 17546996
TI  - Modelling biofilm-modified hydrodynamics in 3D.
AB  - A simulation-based study to predict the impact of biofilm growth on displacement
      distributions for flow of water through a supporting packed bed is presented. The
      lattice Boltzmann method and a directed random walk algorithm are used, and are
      applied to the system with and without biofilm being present. The aim of this
      simulation study is to model the anomalous transport dynamics induced by biofilm,
      as reported in the literature, and thus to study the impact of observation time,
      delta, on the shape of the displacement distributions (propagators). We believe
      that this is the first demonstration of a propagator simulation for flow through
      a complex porous structure modulated by biofilm growth. The propagator
      distributions undergo a transition from a pre-asymptotic to a Gaussian-shaped
      distribution with increasing delta. The propagators were simulated for a wide
      range of delta going up to 500 seconds. This transition occurs with and without
      biofilm, but is very significantly delayed when biofilm is present due to the
      consequential development of essentially stagnant regions. The transition can be
      classified into three stages: a diffusion-dominated stage, a "twin-peak" stage
      and an advection-dominated stage.

PMID- 17546997
TI  - Experimental and simulation analysis of community structure of nitrifying
      bacteria in a membrane-aerated biofilm.
AB  - Until now, only few attempts have been made to assess biofilm models simulating
      microenvironments in a biofilm. As a first step, we compare the microenvironment
      observed in a membrane aerated biofilm (MAB) to that derived from a two
      dimensional computational model with individual ammonia oxidizing bacteria (AOB)
      and nitrite oxidizing bacteria (NOB) embedded in a continuum EPS matrix.
      Gradients of oxygen were determined by means of microelectrodes. The change in
      nitrifying bacterial populations with the biofilm depth was quantified using
      fluorescence in situ hybridization (FISH) in combination with a confocal laser
      scanning microscopy (CLSM). Microelectrode measurements revealed that oxic and
      anoxic or anaerobic regions exist within the MAB. The oxygen profile predicted by
      the model showed good agreement with that obtained by microelectrode
      measurements. The oxic part of the biofilm was dominated by NSO190 probe
      hybridized AOB, which formed relatively large clusters of cells directly on the
      membrane surface, and by the NOB belonging to genus Nitrobacter sp. On the other
      hand, NOB belonging to genus Nitrospira sp. were abundant at the oxic-anoxic
      interface. The model prediction regarding AOB and Nitrobacter sp. distribution
      was consistent with the experimental counterpart. Measurements of AOB cluster
      size distribution showed that colonies are slightly larger adjacent to the
      membrane than at the inner part of the biofilm. The sizes predicted by the
      current model are larger than those obtained in the experiment, leading to the
      arguments that some factors not contained in the model would affect the cluster
      size.

PMID- 17546998
TI  - Estimation of kinetic parameters of a model for deammonification in biofilms and
      evaluation of the model.
AB  - A systematic approach to estimate and evaluate parameters for deammonification in
      biofilms from available experimental data was evaluated. Parameter estimation was
      based on a regional steady state sensitivity analysis to select relevant
      parameters and design of experiments based on a local identifiability analysis.
      The calibrated model was evaluated under different experimental conditions. Nine
      of the 16 kinetic and stoichiometric parameters had a significant influence on
      model predictions. Of these nine parameters only six kinetic parameters were
      identifiable from batch experiments regardless of the experimental design. More
      parameters were not identifiable due to high correlations between growth rates
      and the corresponding affinity constant for oxygen. Data from a batch experiment
      at 2 mg/L dissolved oxygen (DO) were used to estimate inactivation rates and
      affinity constants for oxygen for ammonium oxidisers (AO), nitrite oxidisers (NO)
      and anaerobic ammonium oxidisers (AN). In addition, it was found that not only
      kinetic and stoichiometric parameters but also the external mass transfer
      resistance significantly affected model predictions. The resulting model was able
      to reproduce batch test and continuous reactor operation where DO concentrations
      were similar to those in the batch experiment used for parameter estimation.
      However, the model overestimated deammonification for a batch experiment at a
      much higher DO concentration (5 mg/L). Thus, parameter values that are
      identifiable and are estimated for given environmental conditions may not
      necessarily be valid for significantly different experimental conditions.

PMID- 17546999
TI  - Toward an operational dynamic model for tertiary nitrification by submerged
      biofiltration.
AB  - This work deals with the methodology put in place to fit and validate the
      parameters of a biofiltration model (BAF) in tertiary nitrification treatment and
      dynamic conditions. For an average loading rate of 0.65 kg NH4-N/m(3) media/d,
      different time loading rates are applied inside a filtration-backwash run using a
      semi-industrial pilot. Comparisons between predicted and observed values on the
      NH4-N, NO3-N and TSS in treated water and the total head loss deltaP are carried
      out firstly using default values of BAF parameters. Model predictions
      overestimate values measured but trends are well reproduced. A sensitivity
      analysis is carried out and the hierarchy of BAF parameters has been set up
      classifying them into strong and low influence on the effluent concentrations.
      Among parameters revealing the strongest influence are those of the filtration
      module and the mean density of biofilm for the TSS effluent and the total AP, the
      specific autotrophic growth rate, the maximum biofilm thickness and the reduction
      coefficient of diffusivity in the biofilm for the NH4-N, NO3-N effluent. Finally,
      this classification leads to setting a calibration procedure, thanks to specific
      experimental tests directly measuring some BAF parameters.

PMID- 17547000
TI  - Modelling and dynamic simulation of a pilot-scale moving bed bioreactor for the
      treatment of municipal wastewater: model concepts and the use of respirometry for
      the estimation of kinetic parameters.
AB  - A model for the simulation of a moving bed bioreactor (MBBR) used for the
      treatment of municipal wastewater is proposed. The model includes attachment of
      particulates to the biofilm and detachment of biofilm into the bulk liquid. The
      growth kinetics are modelled with the activated sludge model no. 1 (ASM1).
      Respirometry was used for the estimation of kinetic parameters. The resulting
      respirograms featured the typical endogenous and exogenous respiration phases and
      the respirogram shapes were as expected from analogous respirometry with
      activated sludge. The estimated parameter set was used for modelling and
      simulation of the pilot-scale MBBR. The main proportion of biomass in the MBBR
      was found to be attached as biofilm on the carrier elements (4.1 -4.6 g dm-3) and
      only a small amount was suspended in the bulk liquid (0.15gdm(-3)). Attachment
      and detachment rates were estimated to be 4.8-7.5g m(-2) d(-1) 1for attachment
      and 6.5-7.5g m(-2) d(-1) for detachment. The biofilm age was estimated to be 1.8
      2.7d. The model was used to predict effluent quality parameters and a good fit of
      the simulated data to the measured data originating from a four-days-long
      measurement campaign was obtained.

PMID- 17547001
TI  - Optimizing and modelling nitrogen removal in a new configuration of the moving
      bed biofilm reactor process.
AB  - A new configuration of the moving-bed biofilm reactor process with pre
      denitrification and nitrification was investigated in a pilot plant, which is fed
      with urban raw wastewater, the primary settler is located between the anoxic and
      the aerobic reactors, and primary sludge is recycled to the anoxic reactor as a
      hybrid pre-denitrification. The carriers used in the experiments are made of high
      density polyethylene, with a diameter of 10 mm and a specific surface area of 400
      m(2)/m(3). The new process was compared with conventional pre-denitrification
      nitrification using in-series reactors fed with settled wastewater. The new
      configuration achieved an increase of 45% for the denitrification rate and of 30%
      for the nitrification rate when compared with conventional configuration. These
      results were analysed in light of the calibration study of the mixed-culture
      biofilm (MCB) model and simulations in AQUASIM 2.1 platform. Regarding
      denitrification, the high values obtained in the new configuration were
      attributed to a higher removal of the slowly biodegradable substrate (Xs) in the
      anoxic reactor due to the use of raw wastewater and sludge recycle. Accordingly,
      the amounts of heterotrophic biomass (XH) and Xs obtained in simulations were
      higher in both the biofilm and the bulk liquid. Regarding nitrification, the
      higher values were attributed to a lower removal of Xs in the aerobic reactors
      and accordingly, a lower accumulation of heterotrophic biomass in the biofilm was
      found in the simulations.

PMID- 17547002
TI  - A biofilm model for engineering design.
AB  - A biofilm model is presented for process engineering purposes--wastewater
      treatment plant design, upgrade and optimisation. The model belongs in the 1D
      dynamic layered biofilm model category, with modifications that allow it to be
      used with one parameter set for a large range of process situations. The biofilm
      model is integrated with a general activated sludge/anaerobic digestion model
      combined with a chemical equilibrium, precipitation and pH module. This allows
      the model to simulate the complex interactions that occur in the aerobic, anoxic
      and anaerobic layers of the biofilm. The model has been tested and is shown to
      match a variety of design guidelines, as well as experimental results from batch
      testing and full-scale plant operation. Both moving bed bioreactors (MBBR) and
      integrated fixed film activated sludge (IFAS) systems were simulated using the
      same model and parameter set. A new steady-state solver generates fast solutions
      and allows interactive design work with the complex model.

PMID- 17547003
TI  - Microbial motility involvement in biofilm structure formation--a 3D modelling
      study.
AB  - A computational model explaining formation of mushroom-like biofilm colonies is
      proposed in this study. The biofilm model combines for the first time cell growth
      with twitching motility in a three-dimensional individual-based approach. Model
      simulations describe the tendency of motile cells to form flat biofilms spreading
      out on the substratum, in contrast with the immotile variants that form only
      round colonies. These computational results are in good qualitative agreement
      with the experimental data obtained from Pseudomonas aeruginosa biofilms grown in
      flowcells. Simulations reveal that motile cells can possess a serious ecological
      advantage by becoming less affected by mass transfer limitations. Twitching
      motility alone appears to be insufficient to generate mushroom-like biofilm
      structures with caps on stalks. Rather, a substrate limitation-induced detachment
      of motile cells followed by reattachment could explain this intriguing effect
      leading to higher-level biofilm structure.

PMID- 17547004
TI  - Study of rotating biological contactor performance in wastewater treatment using
      multi-culture biofilm model.
AB  - The rotating biological contactor (RBC) process offers the specific advantages of
      a biofilm system in treatment of wastewater for removal of soluble organic
      substances and stabilisation of nitrogen compounds. Being a unique adaptation of
      the moving-medium biofilm system, it facilitates easy and effective oxygen
      transfer. However, process optimisation and adaptability under different
      conditions remain challenging tasks for the efficient use of this technology.
      Although modelling helps to study system performance under various external
      conditions, satisfactory mathematical representation is lacking due to the
      dynamic nature of the RBC system. In this work, it has been attempted to frame a
      mathematical model for a three-stage RBC process in simple and realistic ways.
      The model is based on the well-known principles of one-dimensional mass transfer
      and transport of substances. The biochemical conversion process is adopted from
      the Activated Sludge Model No. 3 which represents a mixed-culture biomass
      environment. Owing to the dynamic nature of oxygen transfer, which is the typical
      limiting substrate in municipal wastewaters, the boundary layer is assumed to be
      completely mixed and concentrations averaged over the entire volume. A part of
      the boundary layer is assumed to be exposed to air and the rest submerged in bulk
      liquid at all times. The model results are compared with laboratory-scale
      experimental data available at 25 'C. Sensitivity analysis is performed with the
      model to study the significance of variation of different system parameters or
      the surrounding environment. In essence, the model helps to explore the
      flexibilities within a RBC system and optimise the process design accordingly.

PMID- 17547005
TI  - Performance and microbial ecology of the hybrid membrane biofilm process for
      concurrent nitrification and denitrification of wastewater.
AB  - We report on a novel process for total nitrogen (TN) removal, the hybrid membrane
      biofilm process (HMBP). The HMBP uses air-supplying hollow-fibre membranes inside
      an activated sludge tank, with suppressed aeration, to allow concurrent
      nitrification and denitrification. We hypothesised that a nitrifying biofilm
      would form on the membranes, and that the low bulk-liquid BOD concentrations
      would encourage heterotrophic denitrifying bacteria to grow in suspension. A
      nitrifying biofilm was initially established by supplying an influent ammonia
      concentration of 20 mgN/L. Subsequently, 120 mg/L acetate was added to the
      influent as BOD. With a bulk-liquid SRT of only 5 days, nitrification rates were
      0.85 gN/m(2) per day and the TN removal reached 75%. The biofilm thickness was
      approximately 500 lim. We used DGGE to obtain a microbial community fingerprint
      of suspended and attached growth, and prepared a clone library. The DGGE results,
      along with the clone library and operating data, suggest that nitrifying bacteria
      were primarily attached to the membranes, while heterotrophic bacteria were
      predominant in the bulk liquid. Our results demonstrate that the HMBP is
      effective for TN removal, achieving high levels of nitrification with a low bulk
      liquid SRT and concurrently denitrifying with BOD as the sole electron donor.

PMID- 17547006
TI  - Changes in ammonia oxidiser population during transition to low pH in a biofilm
      reactor starting with Nitrosomonas europaea.
AB  - Recent experiments in our laboratory using both biofilm and suspended biomass
      reactors have demonstrated high rate nitrification at low pH with known
      autotrophic nitrifying bacteria originating from wastewater treatment plants
      refuting previous assumptions that nitrification is significantly inhibited at
      low pH. Since much of the earlier microbiological work regarding ammonia
      oxidising bacteria (AOB) physiology was carried out using Nitrosomonas europaea,
      this model bacterium's capability for high rate nitrification at low pH in a
      continuous biofilm reactor was tested. A biofilm reactor filled with sintered
      glass particles was inoculated with a pure culture of N. europaea. The reactor
      was first operated to high nitrification rates under conditions favourable to N.
      europaea (pH > 7; high ammonium concentrations). To eliminate inhibitory
      concentrations of nitrite at low pH, an enriched culture of Nitrospira (a nitrite
      oxidising bacterium) was then added. The transition from neutral to acidic
      conditions was attempted by sharply lowering the nitrification rate and by using
      a feeding solution containing insufficient buffer for complete nitrification. As
      opposed to other successful transitions, the pH in the N. europaea/Nitrospira
      reactor initially dropped only slightly and maintained pH > 6 for over two weeks.
      The reactor reached pH 4.5 only after four weeks. FISH results showed that while
      the percent of AOB and Nitrospira to eubacteria remained relatively constant at
      51.1 +/- 8.2% and 40.8 +/- 6.4%, respectively, the AOB community changed
      completely in 60 days from 100% N. europaea to 100% Nitrosomonas oligotropha.
      Even though N. oligotropha was not intentionally introduced into the reactor, it
      is apparently much better adapted to conditions of low pH.

PMID- 17547007
TI  - Determination and localisation of in situ substrate uptake by anaerobic
      wastewater treatment granular biofilms.
AB  - Radiotracer incubation experiments and beta microimaging, along with fluorescent
      in situ hybridisation (FISH), are proposed as a complementary approach to
      specific methanogenic activity testing and measurement of in vitro substrate
      utilisation rates to understand better the ecophysiology of anaerobic granular
      biofilms from wastewater treatment reactors.

PMID- 17547008
TI  - Occurrence and persistence of bacterial and viral faecal indicators in wastewater
      biofilms.
AB  - Biofilms within wastewater treatment plants can capture enteric microorganisms
      initially present in the water phase immobilising them either definitively or
      temporarily. Consequently, fates of microorganisms may totally change depending
      on whether they interact or not with biofilms. In this study, we assessed the
      stability of wastewater biofilms comparing the evolution of the concentrations of
      bacteria (heterotrophic plate count [HPC], thermotolerant coliforms [TC]) and
      viral (somatic coliphages [SC] and F-specific phages [F +]) indicators in the
      biofilms and in the corresponding wastewaters at 4 and 20 dgrees C. Additionally,
      we assessed the monthly occurrence of these bacterial and viral indicators as
      well as of pathogenic protozoa (Cryptosporidium oocysts and Giardia cysts) in
      three native wastewater biofilms for four months. Our results show that viral
      indicators (SC and F + ) persist longer in biofilms than in the corresponding
      wastewaters at 4 degrees C as well as at 20 degrees C. In contrast, persistence
      of bacterial indicators (TC and HPC) depends on both the temperature and the
      matrix. Differences between viral and bacterial persistence are discussed.
      Monthly analysis of native wastewater biofilms shows that bacterial and viral
      indicators, as well as Cryptosporidium oocysts and Giardia cysts, attach to
      wastewater biofilms to a concentration that remains stable in time, probably as a
      result of a dynamic equilibrium between attachment and detachment processes.

PMID- 17547009
TI  - Use of fluorescent in situ hybridisation for the visualisation of Helicobacter
      pylori in real drinking water biofilms.
AB  - A fluorescently labelled peptide nucleic acid (PNA) probe has been applied for
      the in situ detection of Helicobacter pylori in drinking water biofilms. The
      method was originally applied to real pipe samples removed from a drinking water
      distribution system (DWDS) but the curvature and the heavy fouling of the pipes
      prevented an accurate detection of the bacterium by epifluorescence microscopy.
      Therefore, two semi-circular flow cells were placed in a bypass of the DWDS, and
      coupons with up to 72 days of exposure were regularly sampled and analysed for
      the presence of H. pylori. In the flat surfaces of the coupons, it was possible
      to sparsely detect cells exhibiting similar morphology to H. pylori that were
      emitting the PNA probe fluorescent signal. Coupons were also visualised under the
      microscope before the hybridisation procedure to serve as negative controls and
      ensure the validity of the method. This work corroborates the findings already
      published elsewhere that this bacterium might be present in DWDS biofilms. The
      method requires, however, highly trained personnel for an accurate detection of
      the pathogen and will need simplification before being routinely used in standard
      water analysis laboratories.

PMID- 17547010
TI  - An ecology-based analysis of irreversible biofouling in membrane bioreactors.
AB  - To provide the first step towards a microbial ecology-based understanding of
      irreversible membrane biofouling, four laboratory-scale membrane bioreactors
      (MBRs) were operated to investigate the identity of bacterial populations highly
      correlated with irreversible membrane biofouling. The conventional MBR was
      divided into two separate experimental units. Unit one consisted of four
      suspended-growth, activated sludge, sequencing batch bioreactors treating a
      synthetic paper mill wastewater. Unit two consisted of a microfiltration membrane
      cell. Amplified ribosomal deoxyribonucleic acid restriction analysis (ARDRA) was
      used to compare the predominant bacterial populations in samples of mixed liquor
      and irreversibly bound to the membrane surface. The results of ARDRA showed a
      significant difference between the planktonic and sessile bacterial communities
      suggesting that irreversible biofouling of microfiltration membranes may be more
      highly correlated to specific bacterial populations rather than the total, bulk
      concentration of biomass. A custom-built mini-flow cell and light microscopy were
      used to visualise the early formation of biofilms by two pure cultures
      (Escherichia coli and Acinetobacter calcoaceticus) on membrane surfaces. The
      results confirmed that A. calcoaceticus was able to enhance the initiation of
      biofilm formation on microfiltration membranes.

PMID- 17547011
TI  - Comparison of some characteristics of aerobic granules and sludge flocs from
      sequencing batch reactors.
AB  - Physical, chemical and biological characteristics were investigated for aerobic
      granules and sludge flocs from three laboratory-scale sequencing batch reactors
      (SBRs). One reactor was operated as normal SBR (N-SBR) and two reactors were
      operated as granular SBRs (G-SBR1 and G-SBR2). G-SBR1 was inoculated with
      activated sludge and G-SBR2 with granules from the municipal wastewater plant in
      Garching (Germany). The following major parameters and functions were measured
      and compared between the three reactors: morphology, settling velocity, specific
      gravity (SG), sludge volume index (SVI), specific oxygen uptake rate (SOUR),
      distribution of the volume fraction of extracellular polymeric substances (EPS)
      and bacteria, organic carbon and nitrogen removal. Compared with sludge flocs,
      granular sludge had excellent settling properties, good solid-liquid separation,
      high biomass concentration, simultaneous nitrification and denitrification.
      Aerobic granular sludge does not have a higher microbial activity and there are
      some problems including higher effluent suspended solids, lower ratio of VSS/SS
      and no nitrification at the beginning of cultivation. Measurement with CLSM and
      additional image analysis showed that EPS glycoconjugates build one main fraction
      inside the granules. The aerobic granules from G-SBR1 prove to be heavier,
      smaller and have a higher microbial activity compared with G-SBR2. Furthermore,
      the granules were more compact, with lower SVI and less filamentous bacteria.

PMID- 17547012
TI  - Using microbial genomics to evaluate the effectiveness of silver to prevent
      biofilm formation.
AB  - Increasingly, monovalent silver cations are being considered as an alternative
      biocide in water distribution systems. The objective of this study was to
      understand how bacteria respond when challenged with silver. The approach used
      included cultivation of Escherichia coli in planktonic and sessile phases,
      exposing biomass to a solution of silver nitrate and evaluating genetic responses
      using commercial Affymetrix microarrays. Experimental results showed that lower
      pH enhanced silver toxicity in a dose-dependent manner. Sessile biomass
      demonstrated resistance to silver, and the microarray results indicated that the
      genetic mechanism for silver resistance was similar to the mechanism for copper
      resistance including upregulation of efflux pumps as well as upregulation of
      metal oxidoreductases. The gene, copA, a P-type ATPase efflux flux, was
      upregulated in response to silver exposure, and the gene of CusCFBA, a Cu(I)
      efflux pump, was also upregulated. The gene of CueO, a robust cuprous oxidase,
      was also upregulated and may have reduced silver toxicity through oxidation of
      silver ions. This study is significant because it provides baseline data to
      understand the genetic response of bacteria to silver biocides.

PMID- 17547013
TI  - Cohesion and detachment in biofilm systems for different electron acceptor and
      donors.
AB  - This work deals with the cohesion and detachment in biofilm systems for two
      electron acceptors and for two electron donors. Biofilms were developed on
      plates, under very low shear stress for one month and then subjected to an
      erosion test for two hours in a Couette-Taylor reactor. Biofilm was characterised
      in terms of average thickness and residual TOC mass. It was found that the
      biofilm structure is very heterogeneous and stratified. The top layer, which
      represents 60% of the biofilm mass, is very fragile and can be easily detached;
      the basal layer, which represents 20% of the biofilm mass, is very cohesive and
      can resist shear stresses up to 13 Pa. Between these two layers, a middle layer
      of intermediary cohesion represents 20% of the initial biofilm mass.

PMID- 17547014
TI  - The effect of detachment on biofilm structure and activity: the oscillating
      pattern of biofilm accumulation.
AB  - In our previous papers we have demonstrated that biofilm structure never reaches
      a steady state in biofilm reactors; in this paper we link this fact to biofilm
      detachment and to the oscillating pattern of biofilm accumulation. In one respect
      reactors supporting suspended microbial growth and reactors supporting attached
      microbial growth (biofilms) are similar: in both the biomass accumulates in the
      reactor and is disposed of with the effluent. However, while in reactors with
      suspended microbial growth biomass accumulation and disposal occur
      simultaneously, in biofilm reactors these two processes are separated in time.
      Biomass accumulation in biofilm reactors shows a distinct pattern composed of
      three phases: (1) growth, (2) detachment, (3) regrowth. Despite this distinct
      pattern of biofilm accumulation observed at the microscale, biofilm reactors do
      reach a steady state of substrate removal.

PMID- 17547015
TI  - The role of hydrodynamic stress on the phenotypic characteristics of single and
      binary biofilms of Pseudomonas fluorescens.
AB  - This study investigates the phenotype of turbulent (Re = 5,200) and laminar (Re =
      2,000) flow-generated Pseudomonas fluorescens biofilms. Three P. fluorescens
      strains, the type strain ATCC 13525 and two strains isolated from an industrial
      processing plant, D3-348 and D3-350, were used throughout this study. The
      isolated strains were used to form single and binary biofilms. The biofilm
      physiology (metabolic activity, cellular density, mass, extracellular polymeric
      substances, structural characteristics and outer membrane proteins [OMP]
      expression) was compared. The results indicate that, for every situation,
      turbulent flow-generated biofilms were more active (p < 0.05), had more mass per
      cm(2) (p < 0.05), a higher cellular density (p < 0.05), distinct morphology,
      similar matrix proteins (p > 0.1) and identical (isolated strains -single and
      binary biofilms) and higher (type strain) matrix polysaccharides contents (p <
      0.05) than laminar flow-generated biofilms. Flow-generated biofilms formed by the
      type strain revealed a considerably higher cellular density and amount of matrix
      polysaccharides than single and binary biofilms formed by the isolated strains (p
      < 0.05). Similar OMP expression was detected for the several single strains and
      for the binary situation, not dependent on the hydrodynamic conditions. Binary
      biofilms revealed an equal coexistence of the isolated strains with apparent
      neutral interactions. In summary, the biofilms formed by the type strain
      represent, apparently, the worst situation in a context of control. The results
      obtained clearly illustrate the importance of considering strain variation and
      hydrodynamics in biofilm development, and complement previous studies which have
      focused on physical aspects of structural and density differences.

PMID- 17547016
TI  - Variation in the mechanical properties of a porous multi-phase biofilm under
      compression due to void closure.
AB  - Biofilm properties change drastically from one point to another inside the
      matrix, and from one minute to the next, bringing about similar variations in
      biofilm mechanical properties, both in time and space. In this article, we
      present a theory that quantifies deformation-dependent changes in the mechanical
      properties of a composite porous material that undergoes compression. Such
      changes are a result of the pores either closing (when the biofilm is under
      compression) or opening (when under tension). The theory borrows well-established
      principles of continuum mechanics and is modified to represent a biofilm composed
      of four different phases, three different solid biomass materials (active
      biomass, extracellular polymers and inert biomass) and pores. We see that, when
      the evolution of the volume fractions of the different phases in a uniaxial
      compression test is taken into account, the material "hardens" or becomes stiffer
      as the deformation increases, due to void closure. Once complete void closure is
      achieved, the material reaches its maximum stiffness. Different homogenisation
      schemes are presented and comparisons are performed with stress-strain
      calculations for all of them.

PMID- 17547017
TI  - The role of fouling mechanisms in a membrane bioreactor.
AB  - The present study has aimed to quantify the role of pore blocking and cake layer
      in a laboratory scale hollow fibre membrane module in submerged configuration,
      The membrane reactor (MBR) was fed with raw wastewater, only screened with a 2-mm
      sieve, collected from the Palermo WWTP. The MBR was characterised by an operating
      volume of 190 L and equipped with an aeration system located on the bottom of the
      reactor. The MBR operated for 65 days. The permeate was extracted by imposing a
      constant flux through the membrane (21 Lh(-1) m(-2)). The results confirm the
      importance of pore blocking control during start-up. In particular, it provides a
      rapid irreversible fouling that takes place at the beginning of the filtration
      process, before the deposition mechanism. Therefore, low suspended solids
      concentration in the initial phase causes a fast irreversible fouling. This
      circumstance creates the need for more frequent chemical cleaning after start-up
      without inoculum. Finally, the results underline that the cake has a mainly
      reversible feature.

PMID- 17547018
TI  - Ultrastructure of a bio-electrolytic methanogenic/methanotrophic granular biofilm
      for the complete degradation of tetrachloroethylene in contaminated groundwater.
AB  - The electrolytical methanogenic/methanotrophic coupling (eMaMoC) process was
      tested in a laboratory-scale single-stage reactor for the treatment of
      tetrachloroethene (PCE)-contaminated waters. A water electrolysis cell was placed
      directly in the effluent recirculation loop for the supply of both O2 and H2 to
      the system: H2 serving as the electron donor for both carbonate reduction into
      CH4 and reductive dechlorination. The concurrent presence of O2 and CH4 could be
      used by the methanotrophs for co-metabolically oxidising the chlorinated
      intermediates left over by the anaerobic transformation of PCE. At a PCE inlet of
      33-52 microM and a hydraulic residence time (HRT) of 5.6 days, PCE reductive
      dechlorination to dichloroethene (DCE) was over 95% with a maximum DCE
      mineralisation of 83%. Fluorescence in situ hybridisation with 16S rRNA probes
      related to type I and type II methanotrophic bacteria were utilised to localise
      the methanotrophic communities in the anaerobic/aerobic granules. It evidenced
      that with operational time, along with increasing oxygenation rate,
      methanotrophic communities were specifically colonising onto the outermost layer
      of the anaerobic/aerobic granule.

PMID- 17547019
TI  - Influence of biofilm composition on the resistance to detachment.
AB  - Bacillus cereus and Pseudomonas fluorescens were used to develop monoculture
      biofilms in a bioreactor rotating system using a stainless steel cylinder for
      biofilm formation. The biofilms were allowed to grow for 7 days, exposed
      continuously to a Reynolds number of agitation (ReA) of 2,400. Afterwards, the
      biofilms were characterised in terms of respiratory activity, amount of biomass,
      cellular density, cellular size and total and extracellular proteins and
      polysaccharides. The biofilm mechanical stability was assessed by sequential
      submission of the biofilms to increasing ReA, respectively, 4,000, 8,100, 12,100
      and 16,100. The results showed that P. fluorescens biofilms were five times more
      active, had a higher amount of biomass, cellular density, a reduced cellular size
      and a four-fold higher amount of extracellular proteins and polysaccharides than
      B. cereus biofilms. The application of shear stress forces higher than the one
      under which the biofilm was formed (ReA = 2,400) caused biomass removal. The high
      percentage of removal occurred with the implementation of a ReA of 8,100 for both
      B. cereus and P. fluorescens biofilms. The total series of ReA did not give rise
      to total biofilm removal, as only about 76% of P. fluorescens biofilm mass and
      53% of B. cereus biofilm mass were detached from the cylinders. This latter
      result evidences that B. cereus had a higher mechanical stability than P.
      fluorescens biofilms. The overall results demonstrate that P. fluorescens and B.
      cereus formed physiologically distinct biofilms, B. cereus biofilms mainly being
      constituted by cells and P. fluorescens biofilms largely constituted by
      extracellular proteins and polysaccharides. B. cereus biofilms had a
      substantially higher mechanical stability than P. fluorescens biofilms.

PMID- 17547020
TI  - Texture analysis of spatial biofilm development.
AB  - The quantitative evaluation of images taken during biofilm experiments is an
      important step in determining the relation between biofilm performance and
      biofilm architecture. Whereas areal descriptors are used by some researchers,
      descriptors of biofilm texture have received limited attention. In our research,
      the texture of images documenting long-term biofilm experiments was evaluated
      using a spatial grey level dependence matrices (SGLDM) approach. By calculating
      SGLDM for a wide range of position operators (angle-distance combinations), the
      discriminatory power of this approach was extended. For some descriptors, surface
      plots allowed the direct spatial interpretation of texture. Using principal
      component analysis (PCA) a subset of independent textural descriptors was
      identified. It is suggested to determine textural fingerprints of stages during
      biofilm development by making use of PCA and biplots.

PMID- 17547021
TI  - The rate of iron corrosion for different organic carbon sources during biofilm
      formation.
AB  - The effects of total organic carbon and biofilm on microbial corrosion were
      quantified using serum bottles in a 2 x 2 factorial design. Both organic carbon
      and biofilm bacteria had a significant effect on the iron corrosion rate,
      irrespective of the levels of the other variable (p = 0.05). There was no
      evidence of interaction between organic carbon and biofilm bacteria. Within the
      tested levels, the addition of exogenous organic carbon increased the corrosion
      rate by an average of 3.838 mg dm(-2) day(-1) (mdd), but the presence of biofilm
      bacteria decreased the rate by an average of 2.305 mdd. More iron was released
      from the coupon in response to organic carbon. Powder x-ray diffractometry
      indicated that the scales deposited on the corroded iron surface consisted
      primarily of lepidocrocite (gamma-FeOOH), magnetite (Fe3O4) and hematite (alpha
      Fe203). Corrosion rates by different organic carbon sources, i.e. acetate,
      glucose and humic substances, were compared using an annular biofilm reactor. One
      way ANOVA suggested that the effect of each carbon source on corrosion was not
      the same, with the iron corrosion rate highest for glucose, followed by acetate,
      humic substances and the control. Magnetite was a major constituent of the
      corrosion products scraped from iron slides. Examination of community-level
      physiological profile patterns on the biofilms indicated that acetate was a
      carbon source that could promote the metabolic and functional potentials of
      biofilm communities.

PMID- 17547022
TI  - A dual-electrochemical cell to study the biocorrosion of stainless steel.
AB  - The presence of microorganisms on metal surfaces can alter the local
      physical/chemical conditions and lead to microbiologically influenced corrosion
      (MIC). The goal of the present work was to study the effect of a mixed aerobic
      anaerobic biofilm on the behaviour of stainless steel (316 L) in underground
      conditions. Rather than testing different bacteria or consortia, investigations
      were based on the mechanisms of MIC. Mixed biofilms were simulated by the
      addition of glucose oxidase to reproduce the aerobic conditions and by sulphide
      or sulphate-reducing bacteria (SRB) for the anaerobic conditions. A double
      thermostated electrochemical cell has been developed to study the coupling
      between aerobic and anaerobic conditions. Results suggested a transfer of
      electrons from the stainless steel sample of the anaerobic cell to the stainless
      steel sample of the aerobic one. Inorganic sulphide was replaced by SRB in the
      anaerobic cell revealing an increase of the galvanic current which may be
      explained by an effect of lactate and/or acetate on the anodic reaction or by a
      high sulphide concentration in the biofilm. The results of this study underline
      that the dual-electrochemical cell system is representative of phenomena present
      in natural environments and should be considered as an option when studying MIC.

PMID- 17547023
TI  - National Breastfeeding Awareness Week.

PMID- 17547024
TI  - Job guarantee for newly-qualified midwives?

PMID- 17547025
TI  - Campaign for normal birth: less intervention.

PMID- 17547026
TI  - IDM: a day for midwives across the globe.

PMID- 17547027
TI  - The effect of position.

PMID- 17547028
TI  - Skills drills training: the way forward.

PMID- 17547029
TI  - Discrimination: pregnant at work.

PMID- 17547030
TI  - Retention and return in the NHS in England.

PMID- 17547031
TI  - Conference motions 2006: action update.

PMID- 17547032
TI  - Direct entry: equipped for competence?

PMID- 17547033
TI  - PRECOG: detecting pre-eclampsia early.

PMID- 17547034
TI  - Midwifery in New Zealand.

PMID- 17547035
TI  - Sustaining innovation.

PMID- 17547036
TI  - Payment by results: speaking in code.

PMID- 17547037
TI  - Professors of midwifery: the emergence.

PMID- 17547038
TI  - Pay 2007: the campaign continues.

PMID- 17547039
TI  - 'Measly' pay rise for midwives.

PMID- 17547040
TI  - A retrospective prevalence study of malaria in an aborigine hospital in Gombak,
      Selangor, Malaysia.
AB  - This was a five-year retrospective study (1999-2004) on the prevalence of malaria
      at the Aborigine Hospital, Gombak, Malaysia. A total of 94 malaria cases was
      analysed. The highest case reports were for the year 2000, with 32 cases (34%),
      and the lowest was in 2004, with only 1 (1%). The majority of cases reported were
      among the Semai tribe (44%), followed by the Temiar tribe (34%) and the
      unspecified tribe (s) (20%). Females (53%) were more commonly affected than males
      (47%). The majority of cases were within the age group 1-5 years (51%).
      Plasmodium falciparum was the most common species reported in this study, at 57%,
      followed by Plasmodium vivax (38%) and 5% mixed infection of P. falciparum and P.
      vivax. Most patients (27%) stayed for more than one month in hospital. Most
      patients came from Kuala Lipis, Pahang, (78%). The most common complication was
      anemia (38%) followed by splenomegaly (18%); only 2% had cerebral malaria. All
      patients were treated with the standard anti-malarial drugs. No deaths were
      reported in this study.

PMID- 17547041
TI  - Strengthening of national capacity in implementation of antimalarial drug quality
      assurance in Thailand.
AB  - Substandard and counterfeit pharmaceutical products, including antimalarial
      drugs, appear to be widespread internationally and affect both the developing and
      developed countries. The aim of the study was to investigate the quality of
      antimalarial drugs, ie, artesunate (ART), chloroquine (CHL), mefloquine (MEF),
      quinine (QUI), sulfadoxine/pyrimethamine (S/P) and tetracycline (TT) obtained
      from the government sector and private pharmacies in 4 Thai provinces: Mae Hong
      Son, Kanchanaburi, Ranong, and Chanthaburi. Three hundred sixty-nine samples of 6
      antimalarial drugs from 27 government hospitals, 27 malaria clinics, and 53
      drugstores, were collected. Drug quality was assessed by simple disintegration
      test and semi-quantitative thin-layer chromatography in each province; 10%
      passed, 100% failed and doubtful samples were sent to be verified by high
      performance liquid chromatography (HPLC) at the Thai National Drug Analysis
      Laboratory, (NL). Fifteen point four percent of ART, 11.1% of CHL and 29.4% of
      QUI were substandard. Based on the finding, drug regulatory authorities in the
      country took appropriate action against violators to ensure that antimalarial
      drugs consumed by malaria patients are of good quality.

PMID- 17547042
TI  - Chemoprophylaxis according to the guidelines on malaria prevention for Japanese
      overseas travelers.
AB  - Mefloquine has been licensed and registered in Japan for chemoprophylaxis against
      malaria since 2001. Guidelines for the prevention of malaria for Japanese
      overseas travelers were published by a group of malaria specialists under the
      auspices of the Japanese Society of Tropical Medicine and the Ministry of Health,
      Labor and Welfare, but not until March 2005. We implemented these guidelines in
      our clinic at the International Medical Center of Japan in Tokyo and, to better
      understand whether these guidelines are optimally useful, we conducted a study of
      Japanese travelers who visited our clinic seeking pertinent information and
      prophylaxis against malaria. The study group comprised 52 individuals who visited
      our clinic during the period October 2004 through June 2005 prior to travel
      abroad. On the basis of the above-mentioned guidelines, mefloquine was given to
      27 of these individuals, 22 of whom were judged to need regular chemoprophylaxis.
      Mefloquine was not recommended to the other 25 individuals because their stays
      abroad would have been too long to avoid possible side effects or too short for
      symptoms to appear. In fact, some were traveling to malaria-free areas. Of the 27
      individuals given mefloquine, 7 (26%) reported side effects, such as headache,
      vertigo, and nausea, 17 (63%) reported no side-effects, and the other 3 (11%)
      were unable to be followed. The diversity of destinations and accompanying
      malaria risks makes it very difficult for us to administer chemoprophylaxis to
      overseas travelers appropriately. The guidelines proved to be somewhat useful,
      but further experience in malaria chemoprophylaxis is needed for physicians to
      provide reliable pre-travel consultation.

PMID- 17547043
TI  - Detection of Toxolasma gondii in captive wild felids.
AB  - Toxoplasma gondii can infect all species of warm-blooded animals, including
      humans, and causes serious diseases in immunocompromized hosts. Live tachyzoites
      derived from serial passage in HeLa culture were used in the Sabin-Feldman dye
      test for detection of Toxoplasma gondii antibody in serum samples of 21 captive
      wild felids including one fishing cat (Prion nailurus viverrina), one leopard
      (Panthera pardus), two flat-headed cats (Prion nailurus planiceps), 6 tigers
      (Panthera tigris), two leopard cats (Felis bengalensis), two clouded leopards
      (Felis nebulosa), 3 pumas (Puma concolor), and 4 jungle cats (Felis chaus).
      Antibodies to Toxoplasma gondii were founded in 9 of 21 felids (42.8%). This
      study revealed that cell culture-derived tachyzoites can be used successfully as
      a source of live organisms in a gold standard Sabin-Feldman dye test, which is
      simpler, cheaper and less ethically sensitive than in vivo inoculation.

PMID- 17547044
TI  - In vivo culture of Cryptosporidium oocysts for laboratory use.
AB  - In the present study, we describe in vivo cultivation to produce oocysts. Seven
      day-old mice were orally infected with 100,000-120,000 Cryptosporidium oocysts.
      On day 8 post-infection, the mice were killed by ether, and the small and large
      intestines collected. A simple extraction procedure was used and purified using
      Ficoll gradient centrifugation. After purification, the oocysts were preserved in
      phosphate buffered saline with antibiotic at 4 degrees C before use.

PMID- 17547045
TI  - Cultivation of Giardia duodenalis in Mongolian gerbils.
AB  - The Mongolian gerbil (Meriones unguiculatus) is susceptible to infection with
      Giardia duodenalis trophozoites. Each animal was orally infected with 0.5 ml
      Diamond's TYIS-33 culture medium containing 10(6) trophozoites. Cysts were then
      collected and concentrated by sucrose gradient centrifugation. G. duodenalis
      cysts were first observed in feces on day 5 post-infection. The characteristic of
      G. duodenalis infection in gerbils was intermittent cyst release. The range in
      the number of cysts released per gerbil for a 4-hour collection period was 0-1.5
      x 10(3).

PMID- 17547046
TI  - Giardiacidal activity of lemon juice, vinifer and vinegar on Giardia intestinalis
      cysts.
AB  - The giardiacidal efficacy of simple disinfecting materials, ie lemon juice,
      vinifer, and vinegar, for uncooked foods with Giardia cysts was investigated to
      help travelers in Giardia-endemic areas. The cysts were obtained from stools of
      individuals with Giardia intestinalis infection by modified sucrose gradient
      procedure. A pooled batch of 3 x 10(4)/ml Giardia cysts was made from all
      specimens. The cysts were kept at 4 degrees C until use. Before each experiment,
      the number of cysts was determined by hemocytometer. Two sets of Eppendorf tubes
      were used for the experiments, one set at 4 degrees C and one at 24 degrees C.
      One thousand microliters each of lemon juice, vinifer, or vinegar was poured into
      each tube, and 1,000 microl of Giardia cysts were added. Variables were
      disinfectant materials, temperature, and time of exposure. Cyst viability 140 was
      determined by eosin inclusion procedure. Viability of at least 250 cysts in each
      tube at 0, 0.5, 1, 2 and 3 hours after the beginning of the experiments was
      determined. The mean giardiacidal activity at 4 degrees C after 3 hours for lemon
      juice, vinifer, and vinegar was 18.9, 12.8, and 28.4%, and at 24 degrees C, 28.3,
      16.2, and 40.6%, respectively. In conclusion, the giardiacidal activity of
      vinegar was more than the other materials, and as exposure time and temperature
      increased, giardiacidal activity also increased; the highest giardiacidal
      activity of vinegar was at 3-hours exposure at 24 degrees C.

PMID- 17547047
TI  - The exsheathment of Necator americanus infective larvae.
AB  - Infective 3rd-stage larvae of Necator americanus were treated with human sweat
      under various conditions, and compared with human serum, 1.5% saline solution,
      and distilled water. The infective larvae were observed under inverted
      microscopy. The highest percentage (14.0%) of the exsheathed larvae was found in
      human sweat after 2 hours' incubation at 37 degrees C. The proportion of
      exsheathed larvae in human sweat was significantly different from human serum
      (p<0.001), 1.5% saline solution (p<0.001), and distilled water (p<0.001). This
      may reflect the effect of human sweat on the process of skin penetration by
      Necator americanus larvae.

PMID- 17547048
TI  - Randomized comparative trial of two high-dose albendazole regimens for
      uncomplicated human strongyloidiasis.
AB  - A randomized trial study was conducted comparing the efficacy of two high-dose
      regimens of albendazole for the treatment of uncomplicated human
      strongyloidiasis. Agar plate culture (APC) was used as an evaluation technique
      for coprological diagnosis. All 115 subjects infected with Strongyloides
      stercoralis from 7 provinces in northeastern Thailand were divided randomly into
      two groups. Regimen-1 group received albendazole 800 mg/day twice daily for 3
      consecutive days, and regimen-2 group received the same dose for 5 consecutive
      days. For each regimen, the same treatment was repeated once 7 days later. Stools
      were parasitologically examined at 14 days, and 10 days after the second course
      of treatment, respectively. A coprological cure rate of 87.9% (51/58) was
      obtained in the regimen-1 group, with 89.5% (51/57) in the regimen-2 group, which
      was not statistically significantly different (P = 0.794). The mild adverse
      effects were not statistically different between the two groups, at 8.6% and
      8.8%, respectively (P = 0.977). We therefore suggest albendazole treatment using
      regimen 1 should be recommended. However, the use of new effective drugs should
      be considered, especially in hyperinfective strongyloidiasis.

PMID- 17547049
TI  - Anisakids in marine fish from the coast of Chon Buri Province, Thailand.
AB  - A total of 1,600 specimens, consisting of 16 different species of marine fish,
      were dissected and examined for anisakid larvae and adults in visceral organs,
      abdominal cavity, and muscles. One species of adult-stage nematode was found in
      two of 16 species of marine fish studied, Johnius carouna and Dendrophysa
      russelli. No anisakid larvae (third-stage) was found in any of the 16 species of
      marine fish studied. Morphological study of the adult-stage nematode showed
      similar morphology to Anisakis simplex. We found that the nematode adult
      recovered from the marine fish differed from other anisakids in morphology, life
      cycle and locality of infection in the fish. The anisakid adults recovered were
      ovoviviparous or larviparous, but not oviparous as is seen in most other
      anisakids. The intensity and prevalence of nematode infection in Johnius carouna
      were 2.4 and 31.7%, respectively, and in Dendrophysa russelli 3.9 and 87.5%,
      respectively.

PMID- 17547050
TI  - The observation of microfilarial rate and density in cats inoculated with
      increasing numbers of Brugia pahangi infective larvae.
AB  - Having close kinship to Brugia malayi, B. pahangi is a member of the family
      Filariidae, which causes lymphatic filariasis in dogs and cats. Although this
      nematode is unlikely to cause a zoonotic disease in humans, study of the B.
      pahangi life cycle may help control human filariasis. The objective of this study
      was to examine microfilarial rates and densities of B. pahangi in experimentally
      induced infections in cats as a relative measurement. Cats were infected with 3
      different amounts of 3rd-stage larvae (L3); 100, 300 and 500. Cats infected with
      100 L3 became patent for microfilariae longer than the other groups (mean100 =
      99+/-44 days). In comparison, the pre-patent period of B. pahangi was somewhat
      shorter in cats with 300 and 500 L3 infections (mean300 = 76+/-13 and mean500 =
      63+/-5 days). The microfilarial densities of these cats were also determined; the
      density of microfilariae (mf/1 ml blood) increased relative to the duration of
      infection. One-way ANOVA tests were used to compare the microfilarial densities
      of the cats with varying numbers of L3. We found that the microfilarial density
      of cats with 500 L3 exhibited significant differences (p < 0.05) from cats with
      300 and 100 L3. However, we concluded that the amount of microfilariae produced
      in the blood circulation of these cats were not increasing relative to the
      numbers of L3 taken by the host.

PMID- 17547051
TI  - Enzyme markers to identify and characterize Opisthorchis viverrini in Thailand
      and Lao PDR.
AB  - We conducted an allozyme electrophoretic study to explore potential enzyme
      markers to distinguish Opisthorchis viverrini in Thailand and Lao PDR. Twenty
      eight enzymes encoding presumptive 32 loci were established. The enzymes glucose
      6-phosphate dehydrogenase and pyruvate kinase were diagnostic between two
      geographically separate isolates from Thailand. Twelve enzymes, ie, aconitate
      hydratase, aldolase, creatine kinase, enolase, esterases, fumarate hydratase,
      aspartate aminotransferase, glucose-phosphate isomerase, alanine
      aminotransferase, isocitrate dehydrogenase, malic enzyme, and pyruvate kinase,
      also provided diagnostic markers for these two isolates from Thailand and one
      isolate from Lao PDR.

PMID- 17547052
TI  - Application of multiplex pcr for species discrimination using individual
      metacercariae of Paragonimus occurring in Thailand.
AB  - A total of 6 lung fluke species have been documented in Thailand, of which P.
      heterotremus is the most important, since it affects humans. Although P.
      westermani is found as metacercariae in the same crab species as P. heterotremus
      in Thailand, human infections with P. westermani have not been confirmed. To
      accurately discriminate between the individual metacercariae of these two
      species, we established a multiplex PCR method. Using this method, two products
      each were amplified from the metacercarial DNA samples of P. heterotremus (ca.
      310 and 520 bp) and P. westermani (ca. 140 and 520 bp). In contrast, 520-bp
      products alone were found to be generated from the DNA samples of P. siamensis,
      P. bangkokensis and P. harinasutai, 3 other species of lung flukes known to occur
      in Thailand. Digestion of these 520-bp products with the restriction enzyme ScrFI
      could unequivocally discriminate species by the number and size of the produced
      band(s): 3 bands (ca. 60, 210 and 250 bp) for P. harinasutai, 2 bands (ca. 250
      and 270 bp) for P. bangkokensis, and an uncut band (520 bp) for P. siamensis. The
      established multiplex PCR used in combination with restriction enzyme digestion
      (PCR-RFLP with ScrFI) is effective for discriminating the 5 different species of
      lung flukes occurring in Thailand, even at the metacercarial stage.

PMID- 17547053
TI  - Possible discovery of Chinese lung fluke, Paragonimus skrjabini in Manipur,
      India.
AB  - To obtain more information about Paragonimus species prevalent in Manipur, India,
      hundreds of freshwater crabs, Potamiscus manipurensis, were captured from
      mountain streams in the Motbung Mountains in Senapati District, from December
      1997 to January 1998. Crab extracts were prepared by digestion, differential
      filtration, and sedimentation. The filtered sediments were critically examined
      under a stereomicroscope. Isolated Paragonimus metacercariae were used for
      morphological study and animal experimentation. Forty-seven metacercariae were
      fed orally to a 3-month-old male puppy of local breed; at autopsy 155 days after
      inoculation, 12 adult worms were recovered; 2 were free in the thoracic cavity
      and 5 pairs were in lung cysts. Two adult worms were flattened and fixed in 70%
      ethanol and the remaining worms were put directly into 70% ethanol and preserved
      until July 2005. The former 2 worms were stained with borax carmine for
      morphological study at Sikkim Manipal Institute of Medical Sciences, Sikkim,
      India. Two adult worms in the latter group were sent to the National Institute of
      Infectious Diseases, Tokyo, Japan, for morphological identification and DNA
      sequencing. The morphological features of the borax carmine-stained worms were
      characteristic of P. skrjabini, although no genetic material for PCR
      amplification and sequencing could be extracted from the worm.

PMID- 17547054
TI  - A new record of Paragonimus other than P. westermani in southern Thailand.
AB  - Field surveys of Paragonimus in Surat Thani Province, southern Thailand, revealed
      a new record of a lung fluke species other than P. westermani. The metacercariae
      were obtained from the crab, Ranguna smalleyi. The cysts of the metacercariae
      were spherical in shape and the larval body in the cysts contained pinkish
      granules. Fully mature adult worms were obtained from experimental infections
      with a rat and a ferret. The adult worms from the two host animals resembled each
      other, except for size, and had the anatomical characteristics of P.
      bangkokensis, ie the cuticular spines were arranged mainly in groups, the ovaries
      were highly branched, while the testes were more simply divided. Chromosomal
      preparations of the testes showed a haploid number of 11. As no sequence data of
      P. bangkokensis has been deposited in the GenBank/EMBL/DDBJ nucleotide database,
      the ITS2 region was sequenced using the metacercariae as starting material. A
      similarity search of P. bangkokensis ITS2 sequence using the BLAST program
      revealed that there was only one base difference between this population and P.
      harinasutai occurring in central Thailand. The result may suggest a close
      relationship between P. bangkokensis and P. harinasutai. This is the first
      description of Paragonimus species other than P. westermani occurring in southern
      Thailand.

PMID- 17547055
TI  - Dna quantities and qualities from various stages of some trematodes using optical
      and HAT-RAPD methods.
AB  - The aim of this experiment was to minimize DNA quantity and quality for detection
      by optical (spectrophotometer at 260 nm and 280 nm) and HAT-RAPD methods. Total
      DNA from different stages, adult, metacercaria and eggs of 6 trematode species
      were isolated for analysis. In this experiment, the adult trematodes were
      classified into 3 groups by size: small, Haplorchis taichui and Stellantchasmus
      falcatus; medium, Opisthorchis viverrini and Ganeo tigrinus; and large,
      Paramphistomum epiclitum and Fischoederius elongatus. The adult minimal DNA
      quantities and qualities of all specimen samples detected by optical method were
      97.22,72.28, 3,167.00, 1,490.62, 21,382.66, and 27,321.77 ng; eggs were 3.92,
      3.57, 3.72, 6.23, 17.53, and 14.01 ng, respectively; and metacercarial stages
      50.70 and 40.98 ng in H. taichui and S. falcatus. In addition, the HAT-RAPD
      technique was chosen to amplify the minimal DNA qualities and quantities of all
      trematode specimens. Total DNA was 1-1 x 10(-12) ng; DNA templates in each
      dilution were used for amplification by primer OPA-09. DNA concentrations ranging
      between 1 x 10(-8) and 1 x 10(-11) ng were amplified with high polymorphism. Our
      experiment concluded that only a single specimen of each egg, metacercaria, or
      adult stage could be amplified with distinct bands.

PMID- 17547056
TI  - Chronological observations of intestinal histopathology in rats (Rattus
      norvegicus) infected with Centrocestus caninus.
AB  - Intestinal pathological enzyme activity changes were studied chronologically in
      rats after Centrocestus caninus infection. A single inoculation of 300
      metacercariae isolated from the gills of goldfish (Carassius auratus), was orally
      administered to male rats (n = 15). Uninfected animals were used as controls (n =
      5). At days 3, 7, 14, 21, and 28 post-infection (PI), three infected rats, and
      one from each control group, were sacrificed. The duodenum, jejunum, and ileum
      were removed separately and fixed in 10% formalin and 10% cold formal calcium
      solution for histopathological and alkaline phosphatase activity investigations,
      respectively. The worms were found intruded into the intervillous space of the
      mucosa and the mucosa showed villous atrophy, crypt hyperplasia and stromal
      inflammation with inflammatory cell accumulations. Alkaline phosphatase (ALP)
      activity also showed retardation. However, it seemed that these phenomena would
      return to normal at the end of the experiment. It can be concluded, from our
      data, that C. caninus could cause mild histopathological alterations and reduce
      ALP activity in the small intestines.

PMID- 17547057
TI  - Neurocysticercosis: clinical manifestation, neuroimaging, serology and molecular
      confirmation of histopathologic specimens.
AB  - Diagnosis of neurocysticercosis (NCC) is usually based on neuroimaging and/or
      immunological analysis of cerebrospinal fluid (CSF) and/or serum samples for
      detection of specific antibodies against T. solium antigens. Additional
      confirmative diagnosis may be possible by morphological and molecular
      confirmation of resected histopathologic specimens. The majority of NCC cases do
      not always show typical neuroimaging figures with invaginated scolex. So,
      serology using highly specific antigens of T. solium, either semi-purified native
      or recombinant antigens, is essential for confirming NCC cases. There is some
      debate about the usefulness of CSF and serum for immunodiagnosis. When NCC cases
      with a solitary cyst or with calcified lesions are examined, serology is not
      always sensitive to differentiating such cases. Malignant brain tumor is most
      commonly suspected in Japan and is often treated surgically as an urgent task, if
      the clinicians have no experience of NCC cases. Only histopathological specimens
      are expected to show direct evidence of T. solium cysticercosis. Morphology is
      not always sufficient for identification of the Taenia species, even if the
      majority of cysticerci in the human brain are expected to be T. solium. Crucial
      confirmation is based on molecular identification. In this review, these four
      issues are briefly summarized.

PMID- 17547058
TI  - Towards the international collaboration for detection, surveillance and control
      of taeniasis/ cysticercosis and echinococcosis in Asia and the Pacific.
AB  - Both cysticercosis and echinococcosis are potentially among the most serious
      helminth zoonoses threatening human health worldwide. However, due to the lack of
      reliable tools for confirmation or identification of patients or infected
      animals, epidemiological data are expected to be underestimated. Conversely,
      sometimes, such data are over estimated due to the lack of specificity. The most
      important issue for doing field surveys is that they use evidence based science.
      In this communication, advanced immunological and molecular tools for detection
      of individuals infected with either metacestodes or adult tapeworms are briefly
      overviewed, and the applications of such tools for epidemiological surveys in
      Indonesia, China and other countries are introduced. As immunological tools are
      based on antigen-antibody responses, there may exist some cross-reactions.
      Therefore, immunodiagnostic tools are expected to be useful for primary
      screening, and should be combined with confirmation of direct parasitological
      evidence (morphology or DNA), and imaging techniques for cysts. As a risk factor
      for human cysticercosis is the presence of tapeworm carriers, detection of
      taeniasis cases and differentiation of the three human Taenia species (Taenia
      solium, T. saginata and T. asiatica) in Asia and the Pacific requires
      consideration. Similarly, in northwest China, Echinococcus granulosus and E.
      multilocularis are coendemic and differentiation of these species is required in
      humans and definitive hosts. It is stressed that combination of several tools for
      identification of the parasite and for confirmation of diseases is important for
      obtaining highly reliable data before consideration of control of these zoonoses.
      Recent projects coordinated by Asahikawa Medical College have concentrated on
      immunological and molecular diagnostic techniques transferable to colleagues from
      endemic regions of Asia and the Pacific, and on organization of two international
      symposia to establish a platform for further collaboration in the future.

PMID- 17547059
TI  - A case of auricular myiasis in Malaysia.
AB  - Many cases of myiasis have been reported in Malaysia. This is the second reported
      case of auricular myiasis caused by Chrysomya bezziana. The patient was a 41-year
      old, mentally retarded, Orang Asli man. He was brought to the clinic by his
      mother with a complaint of pain and bleeding in his right ear for 3 days. On
      examination, blood and multiple maggots were seen packed in the external auditory
      canal of the right ear. A total of 39 live maggots were removed and maintained
      until they developed into 3rd instar larvae, which were later processed and
      identified as Chrysomya bezziana. The patient was discharged with amoxicillin 500
      mg three times a day for 1 week.

PMID- 17547060
TI  - Pediculus capitis infestation according to sex and social factors in Hamedan,
      Iran.
AB  - Pediculus capitis or head-louse infestation has been a worldwide public-health
      problem, especially among school-aged children. To determine the intensity of
      infestation (abundance) among schoolchildren, children's sex and social factors
      were analyzed as modifiers of the general prevalence of parasitism. The study
      included 847 schoolchildren (407 girls, 440 boys) aged 6-12 years, from 12 public
      rural primary schools of Hamedan, Hamedan Province, Iran. Classic prevalence was
      obtained as the percentage of children with nits and/or lice. The general
      prevalence was 6.85% (girls: 13.5%; boys: 0.7%, p<0.001), head lice were much
      more common in girls than boys. The results showed significant variations in head
      lice infestation, and factors such as parents' literacy, type of hair, previous
      infestation, sharing of bed and comb, and care centers, while there was no
      significant variation between school grade, parents' job, members of family, and
      pediculosis in the studied areas (p>0.05). Sex and social factors are important
      modifiers of P. capitis general prevalence and degree of infestation. The
      classification of children by intensity of infestation allowed a more precise
      delimitation of this condition, which is especially important for disease
      surveillance and application of control measures.

PMID- 17547061
TI  - A new record of Clinostomum philippinensis (Valasquez, 1959) in Trichogaster
      microlepis (Gunther, 1861) from Bung Borapet, Nakhon Sawan, Thailand.
AB  - Thirty-six freshwater fish from Bung Borapet, a large reservoir, were examined
      for helminths in July 2005. The prevalence of infection was 19.44 (7/36) and the
      intensity was 4.67 (168/36) per fish. Seven fish were infected with 4 species of
      helminths: 1 trematode, Clinostomum philippinensis (metacercariae); 1 cestode,
      Senga chiangmaiensis; 1 acanthocephalan, Pallisentis sp and 1 nematode,
      Camallanus anabantis. An encysted metacercaria of Clinostomum philippinensis was
      found in the gills of Trichogaster microlepis. The present study is a new report
      of Clinostomum metacercariae in the second intermediate host, T. microlepsis, in
      Thailand. Future work should investigate the epidemiology of the metacercarial
      stage in the intermediate host and the adult in the experimental definitive host.

PMID- 17547062
TI  - Malacological survey in Phang-Nga Province, southern Thailand, pre- and post
      Indian Ocean tsunami.
AB  - Three malacological surveys were conducted in the Takua Pa District of Phang-Nga
      Province, southern Thailand, before and after the Indian Ocean Tsunami disaster.
      Twenty-nine species of fresh- and brackish-water snails were found, in which 10
      species of freshwater snails were present, including live Pila polita; 8 species
      were of medical importance. Two brackish-water snails, Nerita articulata and
      Littorinopsis scabra, were absent after the tsunami disaster, while brackish
      water Cerithidea cingulata and C. djadjariensis harbored 9 types of trematode
      cercariae.

PMID- 17547063
TI  - Vector competence of Aedes aegypti (L.) and Culex quinquefasciatus (Say) for
      Dirofilaria immitis (Leidy).
AB  - This study was performed to examine the vector competence of Aedes aegypti and
      Culex quinquefasciatus for Dirofilaria immitis. Eleven individual experiments
      were conducted in this study. Nonthaburi and Udon Thani strains of Ae. aegypti
      were allowed to feed on infected dogs that had 5,750 and 4,600 microfilariae (mW)
      per ml of blood, respectively. Three groups of Bangkok-strain Cx.
      quinquefasciatus were allowed to feed on dogs that had 4,800, 5,200, and 5,850 mf
      per ml of blood. Six groups of Liverpool-strain Ae. aegypti were allowed to feed
      on dogs with 1,650, 1,950, 3,350, 9,000, 9,250, and 11,550 mf per ml of blood.
      Three to 4% of Nonthaburi-strain, and 0-6% of Udon Thani-strain Ae. aegypti
      became infected and had infective-stage larvae (L3) of D. immitis in their
      probosces. Zero to 1 and 7% of Bangkok-strain Cx. quinquefasciatus had L3 in
      their probosces after taking blood meals with 4,800 and 5,850 mf per ml of blood,
      respectively. The percent-infected Liverpool-strain Ae. aegypti with L3 in their
      probosces were 3-12, 0-12, 10, 16, 7-19, and 0-21 after taking blood meals with
      1,650, 1,950, 3,350, 9,000, 9,250, and 11,550 mf per ml of blood, respectively,
      when tested at different post-blood-feeding days. This study showed both Ae.
      aegypti and Cx. quinquefasciatus from Thailand can become vectors for D. immitis;
      however, Liverpool-strain Ae. aegypti are more likely to be competent vectors for
      D. immitis than Ae. aegypti and Cx. quinquefasciatus from Thailand. The percent
      infection rates of Ae. aegypti and Cx. quinquefasciatus with D. immitis in the
      field in Thailand need to be investigated, to confirm the role of these
      mosquitoes in the life cycle of D. immitis in nature.

PMID- 17547064
TI  - Entomological studies of Phlebotomus papatasi and P. sergenti (Diptera:
      Psychodidae) as vectors of cutaneous leishmaniasis in Shiraz, Iran.
AB  - Leishmaniasis is considered endemic in 82 countries, including Iran. In order to
      control the vectors of leishmaniasis, entomological studies, such as fauna,
      seasonal abundance, nocturnal activity, sex ratio, resting site, etc, are
      necessary. In this investigation, the species composition of sandflies. and the
      seasonality and nocturnal activity, sex ratio, and resting site, of Phlebotomus
      papatasi and P. sergenti, for implementation of future control measures, were
      surveyed in northeast Shiraz City, southern Iran. Two thousand, five hundred
      (2,500) adult sandflies were collected from internal and external fixed places by
      sticky trap. SPSS version 1.3 software was used to analyze the data.
      Meteorological data were obtained from the meteorological organization in Shiraz.
      In this investigation, a total of 4 species were recorded: P. papatasi, P.
      sergenti, Sergentonmyia sintoni, and Ser. dentata. Peak abundance of both P.
      papatasi and P. sergenti occurred in September, and declined by December. Between
      sunset and sunrise, the maximum and minimum abundance were found to be at 20 00
      hour, and 05 00 or 06 00 hour, respectively. The sex ratio (F/M) of the P.
      papatasi varied from a high ratio of 10.9: 1 in October, to a low ratio of 1.2: 1
      in June. The abundance of sandflies in the external regions was significantly
      more (p<0.05) than the internal regions in all months except May and June. Using
      the results of this investigation, health workers in this area can better manage
      the control and prevention of cutaneous leishmaniasis.

PMID- 17547065
TI  - Insecticide susceptibility of mosquitoes invading tsunami-affected areas of
      Thailand.
AB  - In order to control the mosquitoes invading tsunami-affected areas of Thailand,
      the insecticide susceptibility status of field larvae and mosquitoes (Anopheles
      sundaicus and Culex sitiens) was tested under laboratory conditions. Larval
      bioassay tests were conducted using the WHO standard method. Three larvicides:
      temephos, malathion, and plant extract (ethanolic extract of the Southeast Asian
      long pepper. Piper retrofractum Vahl), were used in the experiments. The results
      revealed that Cx. sitiens was more susceptible to temephos than malathion and the
      plant extract, with LC50 ranges of 0.0008-0.0014 mg/l, 0.0046-0.0078 mg/l, and
      5.3180-10.1030 mg/l, respectively. Cx. quinquefasciatus showed greater tolerance
      to every tested larvicide than Cr sitiens. Adult bioassay tests using a WHO test
      kit and diagnostic doses of 5% malathion, 0.75% permethrin, 0.05% deltamethrin,
      and 4% DDT were also conducted. The results revealed that Cx. sitiens and An.
      sundaicus were susceptible to all tested insecticides. The LT50 of 5% malathion
      ranged between 25.7-26.0 minutes for Cx. sitiens, and 44.7 minutes for An.
      sundaicus. In addition, Cx. quinquefasciatus showed susceptibility to malathion,
      with LT10 of 19.7 minutes. However, it showed resistance to both pyrethroid
      insecticides, with LT50 of 33.1 minutes for 0.75% permethrin, and 19.6 minutes.
      for 0.05% deltamethrin; it showed low percentage mortality at 24 hour post
      exposure, of 48 and 32%, respectively. In conclusion, every tested larvicide
      could be used for controlling Cx. sitiens larvae, even in brackish water,
      pyrethroid insecticides for adult Cx. sitiens and An. sundaicus, and malathion
      for all three species.

PMID- 17547066
TI  - Bioactivity of citrus seed for mosquito-borne diseases larval control.
AB  - This study aimed to determine the activity of citrus-seed extract against Ae.
      aegypti and Cx. quinquefasciatus larvae. The results indicated that ethanol
      citrus-seed extract showed the best killing effect on Ae. aegypti larvae,
      followed by local liquor, and water, with LC50 of 2,267.71, 6,389.22, and
      135,319.40 ppm, respectively, whereas against Cx. quinquefasciatus larvae, the
      LC50 were 2,639.27, 5,611.66, and 127,411.88 ppm, respectively. Temephos was
      tested against Ae. aegypti larvae; the LC50 was 0.00057 ppm, which was nearly
      4,000,000 times less than ethanol citrus-seed extract. When ethanol citrus-seed
      extract and temephos were tested with Nile tilapia (Oreochromis niloticus), a
      standard environmental organism, using LC50 of Ae. aegypti larvae at 2,267 and
      0.00057 ppm, respectively, fish mortality was 0%. The results suggested that
      ethanol citrus-seed extract had no harmful effect on the fish, and that temephos,
      which is recommended by WHO, was safe for use in drinking water. However, when
      the LC50 dose that killed Ae. aegypti larvae for local liquor (6,389 ppm) and
      water extract (135,319 ppm) were tested with fish, the mortality rates were 35%
      and 100%, respectively. On the whole, the results suggested that ethanol citrus
      seed extract is environmentally friendly and can be used in the control of Ae.
      aegypti and Cx. quinquefasciatus larvae.

PMID- 17547067
TI  - Differential tolerance of two morphological variants of Culex tritaeniorhynchus
      (Diptera: Culicidae), a Japanese encephalitis vector, to pyrethroid insecticides
      in Mysore, India.
AB  - Five synthetic pyrethroids, deltamethrin, cypermethrin, permethrin, alpha
      cypermethrin, and lambdacyhalothrin, were tested on the larvae of 2 morphological
      variants of Cx. tritaeniorhynchus collected from Mysore City (ground pools) and
      outside Mysore (paddy fields), in Karnataka State, India. The morphological
      characters, ie, length and width of siphon, siphonal index, comb scale numbers,
      pecten teeth numbers, length of anal gills and anal gill index of larvae of two
      Cx. tritaeniorhynchus populations were found to be significantly different
      (p<0.05). To elicit further detail of these two variants, pyrethroid bioassays
      were undertaken. In general, the toxicity ranking of these pyrethroids tested on
      the Cx. tritaeniorhynchus variants from Mysore City was deltamethrin >
      lambdacyhalothrin > cypermethrin > permethrin > alpha-cypermethrin. However, for
      the rural variety it was deltamethrin > lambdacyhalothrin > alpha-cypermethrin >
      permethrin > cypermethrin. Of the 5 pyrethroids tested, deltamethrin was the most
      effective on both variants. Alpha-cypermethrin and lambdacyhalothrin were
      respectively 2.17 and 2.09 times more effective on the city variety (p<0.05),
      based on LC50 values. The results suggest that, in addition to morphological
      differences, the 2 tested varieties of Cx. tritaeniorhynchus also differ in
      susceptibility status.

PMID- 17547068
TI  - Inhibitory potential of Quercus lusitanica extract on dengue virus type 2
      replication.
AB  - This study reports the in vitro inhibitory potential of crude extract of Quercus
      lusitanica (Q. lusitanica) seeds on the replication of dengue virus type 2 (DEN
      2). In vitro antiviral activity of Q. lusitanica extract, assessed in C6/36 cells
      (cloned cells of Aedes albopictus larvae) employing a virus inhibition assay,
      showed dose-dependent inhibition. The Q. lusitanica extract at its maximum non
      toxic concentration of 0.25 mg/ml completely inhibited 10-1,000 TCID50 of virus,
      as indicated by the absence of cytopathic effect (CPE). The low dose of Q.
      lusitanica (0.032 mg/ml) showed 100% inhibition with 10 TCID50 of virus, but only
      50% and 25% inhibition with 100 and 1,000 TCID50, respectively. The NS1 is a
      glycoprotein present in all flaviviruses and appears essential for virus
      viability. To further evaluate Q. lusitanica extract as an antiviral compound, we
      investigated the effect of Q. lusitanica extract on the NS1 protein expression of
      infected C6/36 cells through proteomics technique. The result showed
      downregulation of NS1 protein expression of infected C6/36 cells after treatment
      with this extract. In conclusion, we found that Q. lusitanica extract has a good
      inhibitory effect on the replication of dengue virus type 2, both in conventional
      cell culture and proteomics technique.

PMID- 17547069
TI  - Use of IgM-capture ELISA for confirmation of Japanese encephalitis infections in
      the Philippines.
AB  - In 2001, the Research and Biotechnology Division (RBD) of St Luke's Medical
      Center, in collaboration with the Institute of Tropical Medicine of Nagasaki
      University in Japan, initiated a long-term study of Japanese encephalitis in the
      Philippines. Laboratory confirmation of acute cases of Japanese. encephalitis was
      done by IgM-capture ELISA, which detects anti-JEV immunoglobulin M in
      cerebrospinal fluid (CSF) samples. In the period 2002-2004, a total of 614 CSF
      samples were submitted to RBD, and of these, 11.7% were positive for anti-JEV
      IgM: 17 in 2002, 18 in 2003, 32 in 2004, and 5 in 2005. Positive cases came from
      patients aged 2-77 years. In the 72 positive cases where gender was identified,
      44 were male and 28 female. Possible co-infections with dengue virus were also
      detected by separate testing for anti-dengue IgM by ELISA in 17 CSF samples
      positive for JE.

PMID- 17547070
TI  - Influenza vaccination among the elderly in Bangkok.
AB  - This study aimed to determine the effectiveness of influenza vaccinations among
      the elderly in Bangkok in reducing influenza-like illness (ILI) and influenza
      related complications. Using a non-randomized, controlled, prospective
      methodology, healthy, active people aged 60 years or more, living in the Bangkok
      Metropolitan Administration (BMA) area, were studied. The two study cohorts
      comprised 519 persons in the vaccinated group and 520 in the non-vaccinated
      group. The outcome under study was influenza-like illness (ILI), as reported by
      the study volunteers. The two groups were comparable for most socio-demographic
      characteristics, except for gender, level of education, marital status, and
      smoking habit. The age range was 60-88 years (mean: 68 years). Females
      outnumbered males in both groups, with ratio of female to male of 2.6:1 and 1.9:1
      in the vaccinated and non-vaccinated groups, respectively. The top three co
      morbidities among these groups were hypertension, diabetes mellitus, and heart
      disease, in that order. Only 1% of the volunteers reported lung disease as co
      morbidity. During the 12-month study period, a total of 107 volunteers reported
      ILI in both groups, with 38 persons in the vaccinated group and 69 persons in the
      non-vaccinated group. There were 46 ILI episodes in the vaccinated group, and 86
      in the non-vaccinated group, for a total of 132 episodes. The incidence rates
      rates of influenza in this population, therefore, were 8.9% for the vaccinated
      and 16.9% for the non-vaccinated groups; with a reduction in the rate of reported
      ILI and doctor visits of 8%. Vaccine effectiveness was rated at 47.6%, crude risk
      ratio at 1.9 (1.33-2.75), and adjusted risk ratio at 1.92 (95% CI: 1.25-2.95),
      after adjustment for gender, marital status, education, and smoking habit. No
      complications due to ILI were observed in this population during the study
      period. Hospitalizations during this period were due to non-ILI related causes,
      such as cancer and accident.

PMID- 17547071
TI  - Study on serum transcobalamin II in patients with murine typhus.
AB  - We measured the serum transcobalamin II in murine typhus- infected patients (n =
      16) admitted to the Hospital for Tropical Diseases in 1996-1997, compared with
      healthy controls (n = 60). The results showed that the transcobalamin II (TCII)
      and total serum unsaturated vitaminB12 binding capacity (UBBC) in patients with
      murine typhus (2,126.5 pg/ml, range 1,262-4,568 and 3,771.5 pg/ml, range 1,576
      6,763 pg/ml) were statistically significantly higher than normal subjects (987.5
      pg/ml, range 678-2,000 pg/ml and 1,402 pg/ml, range 932-2,470 ml) (p<0.001).
      Serum TCII levels in patients (63%) were elevated during the febrile period and
      returned to normal post-treatment. These findings suggest that patients with
      murine typhus had stimulation of reticulo-endothelial system, spleen, mesenteric
      lymph nodes, liver and skin and then released TCII into the blood circulation.
      The elevation in TCII may be used for confirming a diagnosis of murine typhus.

PMID- 17547072
TI  - Salmonella lamphun: first isolation of a new Salmonella serovar in Thailand.
AB  - Two isolates of a new Salmonella serovar, Salmonella Lamphun were discovered from
      animal feeds in Thailand, in 2003, which belongs to group C, with antigenic
      formula 6,8:y: 1,2. Both isolates were susceptible to all antimicrobials tested.
      The pulsed field gel electrophoresis pattern of both isolates comprises 11 DNA
      fractions sized 48, 65, 77, 105, 110, 170, 244, 330, 337,453 and 1,135 kbp. Up to
      April 2005, no human or animal infection by this new Salmonella serovar was
      reported.

PMID- 17547073
TI  - Tuberculosis: a resurgent disease in immunosuppressed patients.
AB  - A total of 136 patients, 67 HIV, 69 diabetes mellitus (DM) with or without (+/-)
      end-stage renal disease (ESRD), were registered for tuberculosis treatment at the
      National Tuberculosis Center (NTBC) from May to December, 2003. Ages ranged from
      21-78 years (median 57.7 years) in TB/DM patients, and 21-62 (mean 37.6 +/- 8.3
      years) in TB/HIV patients. TB was significantly found in younger and single HIV
      patients, but in older and married DM patients (p<0.05). Male patients in both
      groups were strongly associated with TB, while females more commonly had TB with
      DM (p<0.05). The majority of these patients were Malays, unemployed, and resided
      in Kuala Lumpur territory; however, no statistically significant difference was
      found between the 2 groups. Smoking, IVDUs and hepatitis C virus (HCV) infection
      were more significantly found in TB/HIV patients and further analysis showed that
      pulmonary TB was strongly associated with HCV infection in these patients
      (p<0.05). Pulmonary TB (62; 89.9%) was the most common type found in both groups
      and was a markedly more common disease location in TB/DM patients, while
      extrapulmonary TB (21; 31.3%) and miliary TB (14; 21%) were significantly higher
      in TB/HIV patients. Cough with or without sputum, fever and loss of appetite
      and/or weight were common clinical presentations in both groups. Nevertheless,
      fever (54; 80.6%) and lymphadenopathy (17; 25.4%) were significantly related to
      TB/HIV patients (p<0.05). Interestingly, the presence of BCG vaccination and
      positive tuberculin skin test were stronger in TB/HIV (27; 40.3%) and TB/DM (20;
      29%) patients, respectively (p<0.05). Overall, regular 6-, 9- and 12-months' anti
      tubercular therapy (ATT) were routine practice, and EHRZ+B6 was the most common
      regimen used. The highest percentage of patients with treatment success were in
      both groups with 6 months' ATT; however, a significantly higher percentage was
      found in TB/DM (24; 34.8%) than TB/HIV (13; 19.4%) (p<0.05). A success rate of 15
      (21.7%) was noted for TB/DM patients with 9 months' ATT, which was similar to
      both groups with the 12-month regimen. A higher percentage failure rate (lost to
      follow-up) was seen in TB/HIV (19; 28.4%) patients. Nine patients were reported
      to have anti-tubercular-drug side-effects, such as drug-induced hepatitis,
      blurred vision, and skin rash. No cases of drug resistance or death were notified
      among these patients.

PMID- 17547074
TI  - Risk of Mycobacterium tuberculosis transmission in an aboriginal village, Taiwan.
AB  - Tuberculosis is the leading cause of death for notifiable diseases in Taiwan. The
      incidence rate of tuberculosis for aborigines is 3.1 times higher than the
      general population, and the mortality rate for the aboriginal population is 3.2
      times higher than the rate for the rest of Taiwan. The proportion of tuberculosis
      retreatment cases among aborigines is higher than the general population, and
      this is why tuberculosis is widespread in aboriginal communities. To determine
      the risk factors for retreatment cases living in an aboriginal village, a case
      control study was performed. From January 2000 to June 2004, a total of 60
      confirmed tuberculosis cases were enrolled. Tuberculosis was diagnosed by chest
      radiograph, sputum-smear microscopy, and culture. Epidemiological data were
      collected by structured questionnaires. Comparisons of proportions were done by
      chi-square test. Of the 60 cases, 19 were retreatment patients. Most education
      levels among the study subjects were elementary and junior high school. The
      majority of occupations were farmer and laborers. The Odds Ratios (ORs) of 'poor
      compliance' and 'not receiving DOTS' in the retreatment-patient group were
      significantly increased compared with the new patient group. In March 24, 2005,
      CDC-Taiwan vowed to halve the tuberculosis incidence and mortality by 2015. To
      accomplish this goal, CDC-Taiwan is investing funds and personnel in the National
      Tuberculosis Plan (2005-2015). The plan commits the government to implementing
      DOTS, to enhance the public health and medical networks for the country,
      especially for aboriginal villagers.

PMID- 17547075
TI  - Mutation in the rpoB gene of the rifampicin resistant M. avium complex strains
      from Thailand.
AB  - Forms of mutation never before described in the rpoB gene are reported for a
      sample of 20 rifampicin-resistant Mycobacterium avium Complex (MAC) strains
      isolated from AIDS patients in Thailand. All strains were analyzed by polymerase
      chain reaction-single strand conformation polymorphism (PCR-SSCP) and polymerase
      chain reaction-DNA sequencing (PCR-DNA sequencing). Sequence analysis of these
      strains revealed that only one strain (5%) has missense mutation at Lys-626 (Thr)
      and the rest of the strains had 15 different silent mutations within a 542 bp
      region of the rpoB gene. Five strains (25%) had a silent mutation at only one
      position, 7 (35%) at 2 positions, 7 (35%) at 3 positions, and 1 (5%) at 7
      positions. The silent mutation at the Ala-630 codon occurred in the largest
      proportion of the strains (15 strains, 75%), followed by the Val-581 in 8 strains
      (40%), Tyr-578 and Thr-600 in 4 strains (20%), and Gly-597 in 3 strains (15%).
      This investigation demonstrates that mutation in the rpoB gene of MAC strains
      from Thailand are more varied than previously reported for RIF MAC strains. PCR
      SSCP screening clearly separated RIFr strains from rifampicin-susceptible (RIFs)
      strains.

PMID- 17547076
TI  - A prospective study of genital infections in Hamedan, Iran.
AB  - A prospective study of genital infections was conducted in a university
      affiliated teaching hospital in Hamedan City, Iran. A total of 540 women were
      recruited and divided into two equal groups: (1) the case group with vaginitis
      (N=270) and, (2) the asymptomatic control group (N=270). Participants were
      interviewed about the occurrence of any vaginal or urethral discharge. Two
      vaginal swabs were obtained for pH testing, KOH and wet mount examination, Gram
      staining and culture at the time of speculum examination. In the case group, the
      prevalence of candidiasis, trichomoniasis, and bacterial vaginosis was 17.2,
      18.1, and 28.5%, respectively. Measurement of vaginal pH in the clinic was the
      single most useful clinical finding for directing empirical therapy. No single
      specimen was found ideal for all pathogens; a cervical swab is better for
      Trichomonas vaginalis but a vaginal swab is needed for candida and bacterial
      vaginosis. To achieve STD control in this and similar populations, public health
      programs must target asymptomatic infections.

PMID- 17547077
TI  - Vitamin B12 status of Thai women with neoplasia of the cervix uteri.
AB  - The vitamin B12 statuses of Thai women with high- and low-grade cervical
      dysplasia were studied and compared with women with normal cytological smears.
      Serum vitamin B12 and vitamin B12 intakes were assessed, as well as demographic
      characteristics, sexual behavior, reproductive and menstrual history, exogenous
      hormone use, personal and familial medical history, smoking habit, and other risk
      factors. The presence or absence of genital HPV DNA was determined by polymerase
      chain reaction (PCR). Serum vitamin B12 levels in women with normal cytological
      smears were significantly higher than those with both high- and low-grade
      cervical dysplasia (p<0.001). Low vitamin B12 serum levels were significantly
      statistically associated with increased low-grade (OR = 4.08; 95% CI = 1.41
      11.79; p < 0.05) and increased high-grade cervical dysplasia risk (OR = 3.53; 95%
      CI = 1.24-10.04; p< 0.05) for the highest vs lowest quartiles of serum vitamin
      B12. This study indicated a relationship between low vitamin B12 status and
      increased risk of cervical cancer.

PMID- 17547078
TI  - Preliminary study of the effect of vitamin E supplementation on the antioxidant
      status of hemoglobin-E carriers.
AB  - The antioxidant status of hemoglobin-E carriers was studied pre- and post
      treatment with vitamin E for 3 months. Fourteen hemoglobin-E carriers (age =
      21.36 +/- 1.08 years, BMI = 18.32 +/- 1.22 kg/m2) were treated with vitamin E 200
      I.U. daily for 3 months. Fasting blood samples were collected and analyzed for
      erythrocyte superoxide dismutase activity, total antioxidant activity, hemoglobin
      concentration, hematocrit, MCV, Heinz body formation and osmotic fragility test.
      The blood parameters before and after vitamin E treatment were compared. The
      results showed that superoxide dismutase activity in the erythrocytes was
      significantly decreased, while total antioxidant activity in plasma, and the
      osmotic fragility of the erythrocytes, was significantly increased after vitamin
      E supplementation. However, hematocrit, MCV, and Heinz body formation did not
      change significantly. This demonstrated that vitamin E 200 IU could be used as a
      lipophilic antioxidant in red blood cells and could help increase the level of
      antioxidant in hemoglobin-E carriers.

PMID- 17547079
TI  - Hairy-cell leukemia: a rare blood disorder in Asia.
AB  - We report a 68-year-old Indian man who was referred to the Hematology Unit for
      investigation for thrombocytopenia, an incidental finding during a pre-operative
      screening for prostatectomy. Physical examination was unremarkable. There was no
      splenomegaly, hepatomegaly or lymphadenopathy. Complete blood counts showed
      normal hemoglobin and total white cell count with moderate thrombocytopenia.
      Hairy-cell leukemia was diagnosed based on peripheral blood film, bone-marrow
      aspirate and trephine biopsy findings, supported by immunophenotyping results by
      flow cytometry. The purpose of this report is to create awareness of this
      uncommon presentation and to emphasize that a single-lineage cytopenia or absence
      of splenomegaly does not exclude the diagnosis of hairy-cell leukemia. Careful
      attention to morphological detail is important for early diagnosis, especially
      when low percentages of "hairy" cells are present in the peripheral blood and
      bone marrow. Early diagnosis is important to ensure that patients obtain maximum
      benefit from the newer therapeutic agents that have greatly improved the
      prognosis in this rare disorder.

PMID- 17547080
TI  - Mutagenicity study of weeds and common plants used in traditional medicine and
      for animal feed.
AB  - Mutagenicity and antimutagenicity potentials were tested using Ames' test in
      crude distilled water and absolute ethanol extracts from the stems and leaves of
      Peperomia pellucida (Linn.) Kunth, Eichhornia crassipes Solms, Colocasia
      esculenta Schott and Brachiaria mutica (Forssk.) Stapf, and the stems of Musa
      sapientum Linn. No mutagenic effect was found in any of the 10 mg/plate crude
      extracts of these plants for either TA98 or TA100 of Salmonella typhimurium, in a
      direct test and a mutagenic induced test by S-9 mix. Both distilled water and
      absolute ethanol extract of 0.5-10 mg/plate B. mutica showed strong
      antimutagenicity to AFB1, B(a)P and 4NQO in two tester strains. Ethanol extract
      of 0.1-0.5 mg/plate C. esculenta also showed antimutagenicity to AFB1, B(a)P and
      4NQO in two tester strains, but the 0.5-10 mg/plate water extract had an
      antimutagenic effect only for B(a)P in TA98. The ethanol extracts of 5 mg/plate
      B. mutica and 0.5 mg/plate C. esculenta are cytotoxic, as indicated by their
      partial killing effect.

PMID- 17547081
TI  - Safety evaluation of aqueous extracts from Aegle marmelos and Stevia rebaudiana
      on reproduction of female rats.
AB  - The purpose of this study was to evaluate the safety of a Thai medicinal plant,
      Aegle marmelos, and a non-caloric sweetener, Stevia rebaudiana, on the
      reproduction of female rats. Female rats were treated orally with aqueous extract
      of A. marmelos (6%) and S. rebaudiana at various concentrations (0, 0.2, 1, or
      10%) for 60 days (1 ml/day) before mating. The control rats received only
      distilled water. At the end of the treatment period, treated females were mated
      with untreated males and the effects on reproduction were examined at day 14 of
      pregnancy. No notable abnormalities were observed in any of the pregnant rats.
      The number of corpus lutea, implanted and dead fetuses, as well as the sizes of
      the fetuses in the treated rats were not significantly different from those of
      the controls. Based on these results, it may be concluded that aqueous extracts
      of A. marmelos and S. rebaudiana at the concentrations used in this study do not
      alter the reproduction of female rats.

PMID- 17547082
TI  - Toxicological evaluation of Cladophora glomerata Kutzing and Microspora floccosa
      Thuret in albino rats.
AB  - This study aimed to evaluate the toxicity of Cladophora glomerata and Microspora
      floccosa ethanolic extracts in rats. Acute toxicity was tested with a single oral
      administration of the extract at a dose of 25 g/kg bd wt. Mortality, behavior,
      amount of food intake, body weight, and any abnormalities of the visceral organs,
      were observed. The results showed that the extract caused neither mortality, nor
      abnormalities. Subchronic toxicity was tested by administering the extract at
      doses of 0.5 g/kg and 1.0 g/kg for 60 days. Differences in body weight,
      hematology and blood biochemistry (alanine aminotransferase, ALT; aspartate
      aminotransferase, AST; blood urea nitrogen, BUN and creatinine, Cre) were not
      detected among the control and treatment groups. Although the packed cell volume
      of the male rats treated with 1.0 g/kg extract was significantly lower than the
      controls (p< or =0.05), the level was in the standard range for rat hematocrit.

PMID- 17547083
TI  - Effect of Kaempferia parviflora Wall. ex. Baker on sexual activity of male rats
      and its toxicity.
AB  - Kaempferia parviflora Wall. Ex. Baker (Krachaidum) has long been used among Thai
      men for sexual enhancement. The aim of this study was to determine the effect of
      K. parviflora ethanolic extract on the sexual behavior of male rats and its
      toxicity. The experiment was divided into three groups of rats given K.
      parviflora extract at doses of 60, 120, and 240 mg/kg BW for 60 days, whilst a
      control group received distilled water at 1 ml/day per oral. The results showed
      that all groups of male rats had significantly higher courtship behavior during
      the first 10-minute period of observation than in the 2nd and 3rd 10-minute
      periods, except those receiving the highest dose of K. parviflora. They revealed
      the same amount of courtship behavior throughout a whole 30-minute period, which
      was significantly lower than the control group. There was no significant
      difference between treated and control groups in other sexual behaviors; mount
      frequency (MF), intromission frequency (IF), mount latency (ML), or intromission
      latency (IL). Toxicological study revealed no significant difference of
      hemoglobin, WBC or differential cell count. All dosages had no effect on kidney
      and liver function, according to the normal values of blood urea nitrogen (BUN),
      creatinine (Crea), aspartate aminotransferase (AST) and alanine aminotransferase
      (ALT). Nevertheless, the histopathological study showed a morphological change in
      the liver. It was concluded that K. parviflora extract at 240 mg/kg BW reduced
      the time in the first 10 mintues of rat courtship behavior and the use of high
      and chronic doses of K. parviflora in humans should be considered inadvisable.

PMID- 17547084
TI  - Preliminary post-tsunami water quality survey in Phang-Nga province, southern
      Thailand.
AB  - This preliminary water quality survey was performed eight weeks after the tsunami
      hit Phang-Nga Province on 26 December 2004. Water samples collected from the
      affected area, 10 km parallel to the seaside, were compared with water samples
      from the control area approximately 4 km from the seaside, which the tsunami
      waves could not reach. These samples included 18 surface-water samples, 37 well
      water samples, and 8 drinking-water samples, which were examined for microbiology
      and physical-chemical properties. The microbiological examinations focused on
      enteric bacteria, which were isolated by culture method, while physical-chemical
      properties comprised on-site testing for pH, salinity, dissolved oxygen (DO),
      conductivity and total dissolved solids (TDS) by portable electrochemical meter
      (Sens Ion 156). The results of the microbiological examinations showed that water
      samples in the affected areas were more contaminated with enteric bacteria than
      the control area: 45.4% of surface-water samples in the affected area, and 40.0%
      in the control; 19.0% of well-water samples in the affected area, and 7.7% in the
      control. All eight drinking-water samples were clear of enteric bacteria. Tests
      for physical-chemical properties showed that the salinity, pH, conductivity, and
      TDS of surface-water samples from the affected area were significantly higher
      than the control. The salinity, conductivity, and TDS of the well-water samples
      from the affected areas were also significantly greater than those from the
      control area. The surface and well water in the tsunami-affected area have been
      changed greatly and need improvement.

PMID- 17547085
TI  - [Clinical implication and frequency of the incidental finding of endometriosis
      during oocyte retrieval].
AB  - BACKGROUND: Endometriosis is a clinical disease that is associated with poor
      outcomes in in vitro fertilization (IVF) programs with a decrease in oocyte
      retrieval, oocyte quality, implantation and pregnancy rates. When an endometrioma
      is diagnosed, it is indicated to remove endometrial cysts by laparoscopy or
      perform an aspiration before the cycle of IVF. OBJECTIVES: To evaluate the effect
      of endometriosis diagnosed incidentally during oocyte retrieval on the IVF
      outcome, as well as to establish its frequency. MATERIAL AND METHODS:
      Retrospective analysis of 1,000 files of patients who underwent to oocyte
      retrieval between January 2002 and March 2005, in the Centro Especializado para
      la Atenci6n de la Mujer in Mexico City. Of the total procedures tubal factor was
      the first indication for IVF and male factor was on second place. Only in seven
      patients of 1,000 oocyte retrievals was detected the presence of endometriosis
      fluid instead of folicular fluid. RESULTS: The prevalence of endometriosis
      diagnosed incidentally during oocyte retrieval was 0.7%, and the oocyte quality
      was 1.55 (regular). The fertilization rate for patients with endometriomas was
      45% and the implantation and pregnancy rates were zero per cent while the
      patients without endometriomas the fertilization rate was 65% with an
      implantation rate of 18% and the pregnancy rate was 35%. CONCLUSION:
      Endometriosis is a disease that must be treated before an IVF cycle in stages III
      IV and especially in presence of endometriomas because it could affect negatively
      IVF outcomes.

PMID- 17547086
TI  - [Effectiveness of nasal vs oral estrogens in the climacteric syndrome].
AB  - BACKGROUND: Hormone replacement therapy reestablishes the diminished hormonal
      level and reduces mild, moderate and severe effects of climacteric. Its treatment
      includes estrogens, progestagens and a mixture of both. OBJECTIVE: To evaluate
      the efficacy of intranasal and oral estrogens in the climacteric syndrome.
      MATERIAL AND METHODS: 60 patients were evaluated with climacteric syndrome; 30
      received intranasal estrogens (group A) and 30 received oral estrogens (group B).
      Age range, 34-64 years. The symptoms were classified as vasomotor, collagen
      related symptoms and tropic changes. The patients were evaluated four times a
      week, and the symptoms were measured as mild, moderate and severe according with
      the Guia de evaluacion de riesgo en la paciente climaterica. RESULTS: Group A
      (intranasal estrogens) showed faster clinical response in the first two weeks
      (63%), compared with group B (30%). No side effects were found in both groups.
      CONCLUSIONS: Climacteric syndrome can be treated better and faster with
      intranasal estrogens than with oral estrogens, and without side effects.

PMID- 17547087
TI  - [An explanation of depression and anxiety symptoms in sterile women].
AB  - OBJECTIVE: To discriminate variables that could account for depression and
      anxiety in women with infertility. The independent variables were gender role,
      assertive behavior and self-esteem; the dependent variables were depression and
      anxiety. PATIENTS AND METHODS: The sample consisted of 240 women selected through
      a special program intended to choose patients based on infertility medical
      criteria. Five tests translated into Spanish language were administered:
      Masculinity and femininity questionnaire, Assertive behavior questionnaire, Self
      esteem questionnaire, Depression self-assessment scale (ZUNG) and State-trait
      anxiety inventory. Intervening variables were obtained through discriminant
      analysis. Three explaining models were built with p = 0.005. RESULTS: For the
      psychologic variable of the self-esteem, the cut point marked by the instrument
      is 17 points (+/-5), so that, 75% (180) of the women had a normal self-esteem and
      25% (60) obtained a low self-esteem score. As for the anxiety-feature, 60% (144)
      were normal and 40% (96) were over the cut point. For anxiety-state, 52.9% (127)
      were below the cut point and 47.1% (113) over. In depression, the last variable,
      67.9% (163) of them were below and 32.1% (77) over the cut point. CONCLUSIONS:
      Patients showing low self-esteem will tend to show depression and anxiety
      symptoms chronically, no matter their disorder.

PMID- 17547088
TI  - [Preauricular tags: prevalence, clinical characteristics and maternal risk
      factors].
AB  - OBJECTIVE: To determine prevalence and maternal risk factors associated with
      preauricular tags. MATERIAL AND METHOD: A case-control study of 254 newborns with
      isolated preauricular tags not considered part of a syndrome and their controls,
      and who were delivered at the Hospital Civil de Guadalajara Dr. Juan I. Menchaca
      between 1990 and 2003. The maternal risk factors were demonstrated by means of a
      direct interview with the mother. RESULTS: The prevalence of the isolated
      preauricular tags was 1.96 per 1,000 newborns alive, in a 1.2 men for each woman.
      The history of another affected relative was strongly associated with
      preauricular tags (OR 19.28; 95% CI: 4.44-117.60). Infants with preauricular tags
      frequently showed parents consanguinity (OR 3.04; 95% CI: 0.28-76.26), maternal
      age > or =35 years (OR 1.14; 95% CI: 0.53-2.48), exposure to some disease (OR:
      1.23, 95% CI: 0.72-2.12), and drugs use in the first trimester of pregnancy (OR:
      1.11; 95% CI: 0.65-1.92). No associations were found for the frequency of
      abortion, exposure to organic solvents and maternal occupation. CONCLUSIONS: The
      prevalence of isolated preauricular tags in this population was similar to that
      reported in other regions of Latin America, but lower to the prevalences in
      Sweden and Israel. This malformation has an important hereditary component;
      however, it is probably that some teratogenic factors, such as diabetes mellitus,
      can increase its frequency.

PMID- 17547089
TI  - [Mechanism of action of insulin sensitizer agents in the treatment of polycystic
      ovarian syndrome].
AB  - Polycystic ovarian disease (PCOD) is the most important endocrine abnormality
      that affects women in reproductive age. It is characterized by chronic
      anovulation and hyperandrogenemia probably secondary to insulin resistance. Hence
      insulin sensitizers agents had been used in PCOD. Metformin is a biguanide used
      in the treatment of PCOD via decrease of hepatic gluconeogenesis and insulinemia;
      improvement peripheral glucose utilization, oxidative glucose metabolism,
      nonoxidative glucose metabolism and intracellular glucose transport. Such
      effects, when this drug is administered alone during 3 to 6 months, increase sex
      hormone binding globulin (SHBG), reduce free androgens index and hirsutism,
      decrease insulin resistance, and regulate menses in 60 to 70% of cases.
      Thiazolidinodiones are drugs that decrease insulin resistance in the liver with
      hepatic glucose production. Their mechanism of action is through the peroxisome
      proliferator-activated receptors gamma (PPAR-gamma), that help to decrease
      plasmatic concentrations of free fatty acids, pre and postprandial glucose,
      insulin, triglycerides, increased HDL cholesterol and decreased LDL, menses
      return to normality, with improvement of ovulation and decreased hirsutism. It
      seems that by modulation and attenuation of insulin resistance, hypoglucemic
      agents such as metfomin and thiazolidinodiones can be used effectively to treat
      anovulation, infertility and hyperandrogenemia.

PMID- 17547090
TI  - [Burch procedure: experience of 45 years of history].
AB  - It has been 45 years since John C. Burch first described his "colposuspension of
      the Cooper's ligament" technique for the surgical management of stress urinary
      incontinence. Half a century later, his legacy remains alive. His technique, and
      its further modifications, still occupies a privileged place among the surgical
      options for the management of the stress urinary incontinence. Even now, Burch
      procedure is considered the gold standard with which all the other new techniques
      must be compared in order to measure their effectiveness. In the past few years,
      there have been important advances in the knowledge and standardization of the
      female urodynamics. This has increased the accuracy of the medical assessments to
      have a better selection for this surgical procedure. Then, with the technique
      focused on such cases, the results of the procedure have been optimized,
      considering that its complications are not serious and they are relatively
      infrequent. The success rates of this technique are up to approximately 90% in 5
      to 10 years follow-ups and 69% in 10 to 20 years follow-ups. Therefore, it is
      believed that Burch's urethropexia continues contributing greatly to the
      management of the stress urinary incontinence. This revision includes 33
      articles, all of them related with this matter from Ovid database.

PMID- 17547091
TI  - [Recurrent breast haematoma after fine needle aspiration biopsy of angiosarcoma].
AB  - It is reported a rare complication after a fine needle aspiration biopsy of a
      breast angiosarcoma. A 30-years-old female presented with a right breast lump. An
      ovoid, hypoecoic lesion of 39 x 13 mm was detect by ultrasonography. A fine
      needle aspiration biopsy was carried out for diagnosis, but only blood was
      report. After the biopsy the skin showed a violaceous color, the lump was tender,
      reappeared in three instances and increased its size (15 cm). In spite of
      conservative management the pain and the mass did not disappear, then surgical
      management was decided. A soft, violaceous mass of 13 x 6 x 4 cm, with well
      demarcated boundaries was removed. A capillary and cavernous breast hemangioma
      was diagnosed. Four months later a recurrence presented, and a new excision was
      carried out with a resulting moderately differentiated angiosarcoma, then a
      simple mastectomy was performed for definitive treatment. On a literature search
      only one similar case was found. A recurrent haematoma after a fine needle
      aspiration biopsy of a breast tumor mandates to rule out an angiosarcoma.

PMID- 17547092
TI  - [Endometrial ossification: a report of four cases and literature review].
AB  - Endometrial ossification is a rare endometrial pathology. Its predisposing
      factors include history of uterine curettage to metabolic abnormalities. It
      usually presents in patients with secondary infertility and history of first
      trimester pregnancy loss, accompanied by severe dysmenorrhea and dyspareunia. The
      diagnosis is suspected by OB-GYN history and USG findings, therapeutic strategies
      range from D&C to hysterectomy, we propose diagnosis and management by
      hysteroscopy in order to preserve future fertility and minimize uterine damage. A
      review of four cases during 1985-2004 from a large assisted reproduction center
      in Mexico City is presented.

PMID- 17547093
TI  - [Tests of estrogenic substances activity in women. Application to the study of
      etinil-estradiol and of bisdehydrodoisynolic acid. 1952].

PMID- 17547094
TI  - Monitoring and evaluation of integrated disease surveillance and response in
      selected districts in Tanzania.
AB  - Integrated Disease Surveillance and Response (IDSR) is a strategy developed by
      the World Health Organization Regional Office for Africa in 1998. The Ministry of
      Health, Tanzania has adopted this strategy for strengthening communicable
      diseases surveillance in the country. In order to improve the effectiveness of
      the implementation of IDSR monitoring and evaluating the performance of the
      surveillance system, identifying areas that require strengthening and taking
      action is important. This paper presents the findings of baseline data collection
      for the period October-December 2003 in 12 districts representing eight regions
      of Tanzania. The districts involved were Mbulu, Babati, Dodoma Rural, Mpwapwa,
      Igunga, Tabora Urban, Mwanza Urban, Muleba, Nkasi, Sumbawanga Rural, Tunduru and
      Masasi. Results are grouped into three key areas: surveillance reporting, use of
      surveillance data and management of the IDSR system. In general, reporting
      systems are weak, both in terms of receiving all reports from all facilities in a
      timely manner, and in managing those reports at the district level. Routine
      analysis of surveillance data is not being done at facility or district levels,
      and districts do not monitor the performance of their surveillance system. There
      was also good communication and coordination with other sectors in terms of
      sharing information and resources. It is important that districts' capacity on
      IDSR is strengthened to enable them monitor and evaluate their own performance
      using established indicators.

PMID- 17547095
TI  - Pattern and spatial distribution of plague in Lushoto, north-eastern Tanzania.
AB  - A review of plague records from 1986 to 2002 and household interviews were
      carried out in the plague endemic villages to establish a pattern and spatial
      distribution of the disease in Lushoto district, Tanzania. Spatial data of
      households and village centres were collected and mapped using a hand held Global
      Positioning System and Geographical Information System. During the 16-year
      period, there were 6249 cases of plague of which 5302 (84.8%) were bubonic, 391
      (6.3%) septicaemic, and 438 (7.0%) pneumonic forms. A total of 118 (1.9%) cases
      were not categorized. Females and individuals aged 7-18 years old were the most
      affected groups accounting for 54.4% (95% CI: 52.4-56.0) and 47.0% (95% CI: 45
      49) of all reported cases, respectively. Most cases were found in villages at
      high altitudes (1700-1900m); and there was a decline in case fatality rate (CFR)
      in areas that experienced frequent outbreaks. Overall, there was a reduction in
      mean reporting time (from symptoms onset to admission) to an average of 1.35 days
      (95% CI: 1.30-1.40) over the years, although this remained high among adult
      patients (>18 years). Despite the decrease in the number of cases and CFR over
      the years, our findings indicate that Lushoto district experiences human plague
      epidemic every year; with areas at high altitudes being more prone to outbreaks.
      The continued presence of plague in this focus warrants further studies.
      Nonetheless, our findings provide a platform for development of an epidemic
      preparedness plan to contain future outbreaks.

PMID- 17547096
TI  - Susceptibility of Simulium damnosum complex larvae to temephos in the Tukuyu
      onchocerciasis focus, southwest Tanzania.
AB  - Tukuyu onchocerciasis focus was earmarked for vector control using insecticide
      against larval stages. Susceptibility tests of mature larvae of Simulium damnosum
      s.l. vectors to temephos insecticide were carried out before and after two years
      of insecticide treatment of rivers within Tukuyu onchocerciasis focus, south
      western Tanzania. The tests were done in 1999/2000 and 2004 using WHO standard
      methods. Mature larvae were exposed to 9 concentrations of temephos active
      ingredient, from the weakest 0.00975mg/litre to the strongest of 2.5mg/l. Each
      test concentration and control was run in duplicates of 25 larvae each, set for
      three hours in a cool temperature. After incubation, test solution was discarded
      and larval condition checked. Numbers of larvae in each category were recorded
      and used to determine mortality rate for each concentration as well as for the
      LC50 and LC95. A total of 1,666 larvae were tested, 942 during the pre- and 724
      post-treatment. Results showed that both pre and post-treatment samples were
      susceptible, attaining 100% mortality at the diagnostic dose of 1.25mg/l, and
      LC50 between 0.129-0.34mg/l pre - and 0.144-0.211 mg/l (95% CI, P < 0.05) post-
      treatment. These values fall within the standard diagnostic dose of < or =
      0.4mg/l for susceptible S. damnosum s.l populations. It was concluded that the
      endemic S. damnosum population was susceptible to temephos before and after two
      years of intermittent field application. Temephos was thus recommended for
      continued use in onchocerciasis vector control in the Tukuyu focus, to complement
      Community Directed Treatment with Ivermectin, but close monitoring of vector
      susceptibility should be done.

PMID- 17547097
TI  - Characterisation of the Trypanosoma brucei rhodesiense isolates from Tanzania
      using serum resistance associated gene as molecular marker.
AB  - Serum resistance associated (SRA) gene has been found to confer resistance to the
      innate trypanolytic factor (TLF) found in normal human serum; thus allowing
      Trypanosoma brucei brucei to survive exposure to normal human serum. This study
      was carried out to examine the presence of SRA gene and identify the origin of T.
      b. rhodesiense isolates from three districts in Tanzania, namely Kibondo, Kasulu
      and Urambo. Twenty-six T. b. rhodesiense isolates and two references T. b.
      rhodesiense isolates from Kenya were examined for SRA gene using simple
      Polymerase Chain Reaction technique. The gene was found to be present in all 26
      T. b. rhodesiense isolates including the two references isolates from Kenya. The
      SRA gene was confirmed to be specific to T. b. rhodesiense since it could not be
      amplified from all other Trypanozoon including T. b. gambiense; and gave an
      amplified fragment of the expected size (3.9kb), confirming that all these
      isolates were T. b. rhodesiense of the northern variant. Although the geographic
      distributions of T. b. gambiense and T. b. rhodesiense are clearly localized to
      west/central Africa and eastern Africa, respectively, natural movement of people
      and recent influx of large number of refugees into Tanzania from the Democratic
      Republic of Congo, could have brought T. b. gambiense in western Tanzania. The
      overlap in distribution of both of these pathogenic sub-species could result in
      erroneous diagnoses since both trypanosome sub-species are morphologically
      identical, and currently serologic methods have low specificity. Both the
      susceptible and resistant T. b. rhodesiense isolates possessed the SRA gene
      suggesting that there is no correlation between drug resistance and presence of
      SRA gene. The use of SRA gene helps to confirm the identity and diversity of some
      of the isolates resistant to various drugs.

PMID- 17547098
TI  - Malaria specific mortality in lowlands and highlands of Muheza district, north
      eastern Tanzania.
AB  - Vital registration of causes of death in Tanzania is incomplete and many deaths
      occur outside health care settings. Verbal autopsies (VA) are used to determine
      the underlying cause of death, and the probable diagnosis helps to estimate
      reasonably cause-specific mortality. In this paper, we report findings of a
      verbal autopsy survey which involved eight villages in both low and highlands of
      Muheza district, north-eastern Tanzania. The survey was conducted following a
      rapid census, which was done to identify households that had lost one or more
      members within a period of two years from the date of census. Trained research
      assistants administered VA questionnaires to parents/close relatives. Two
      physicians reviewed each report independently and a third opinion was sought
      where there was discordant report between the two. A total of 9,872 households
      were surveyed and 134 deaths were recorded. A total of 96 (71.6%) deaths were
      from lowland villages representing high malaria transmission. Majority (72.4%) of
      the reported deaths occurred at home whilst 32.1% occurred at heath facility
      settings. Overall, severe malaria was the leading cause accounting for 34.3% of
      all deaths. Infants were most affected and accounted for 43.5% of the total
      deaths. Pulmonary tuberculosis ranked second (8.2%) cause of deaths and was
      exclusively confined to individuals > or = 15 years. Probable cause of death
      could not be determined in 13.4% of deaths. In conclusion, majority of deaths in
      rural north-eastern Tanzania occur at home and the immediate causes are usually
      unknown or not documented. These findings indicate that the verbal autopsy is a
      useful tool for detecting leading causes of death at community level in the
      absence of health facility-based data.

PMID- 17547099
TI  - Community knowledge, attitudes and practices towards tuberculosis and its
      treatment in Mpwapwa district, central Tanzania.
AB  - Tuberculosis (TB) is one of the leading causes of adult mortality with 32% of the
      global population infected with Mycobacterium tuberculosis. The current control
      of TB depends mainly on case management using the Direct-Observed Treatment,
      Short-course (DOTs) regimen. Despite the measures taken, the disease burden is
      still on increase especially in the developing countries including Tanzania.
      Correct knowledge and positive perception of the community towards TB and its
      management is a prerequisite to early treatment seeking. This study was carried
      out in Mpwapwa district, central Tanzania, to assess the knowledge, attitudes and
      practice as regards to TB and its treatment. Focus group discussions involving
      men and women were conducted in six villages. Results show that TB was an
      important public health problem. However, community knowledge on its cause was
      poor. Symptoms of TB as mentioned by the community included persistent cough and
      weight loss. TB was reported to be transmitted mainly through air. Self
      medication was the first most preferred option, whereas health care facility
      consultation was the last one. Focus group discussants knew that TB cure requires
      a 8-month period of treatment. Friends and relatives were the main source of TB
      information in the community. In conclusion, rural communities of Mpwapwa
      District have a low knowledge on the causes and the transmission of tuberculosis
      which is a likely cause of the delay in seeking treatment. An intensive
      appropriate community health education is required for a positive behavioural
      change in tuberculosis control.

PMID- 17547100
TI  - Quality of HIV laboratory testing in Tanzania: a situation analysis.
AB  - Tanzania is scaling up prevention, treatment, care and support of individuals
      affected with HIV. There is therefore a need for high quality and reliable HIV
      infection testing and AIDS staging. The objective of this study was to assess
      laboratories capacities of services in terms of HIV testing and quality control.
      A baseline survey was conducted from December 2004 to February 2005 in 12
      laboratories which were conveniently selected to represent all the zones of
      Tanzania. The questionnaires comprised of questions on laboratory particulars,
      internal and external quality control for HIV testing and quality control of
      reagents. Source and level of customer satisfaction of HIV test kits supply was
      established. Of 12 laboratories, nine used rapid tests for screening and two used
      rapid tests for diagnosis. In the 12 laboratories, four used double ELISA and
      five used single ELISA and three did not use ELISA. Confirmatory tests observed
      were Western Blot in three laboratories, DNA PCR in two laboratories, CD4
      counting in seven laboratories, and viral load in two laboratories. Although all
      laboratories conducted quality control (QC) of the HIV kits, only two
      laboratories had Standard Operating Procedures (SOPs). Internal and external
      quality control (EQC) was done at varied proportions with the highest frequency
      of 55.6% (5/9) for internal quality control (IQC) for rapid tests and EQC for
      ELISA, and the lowest frequency of 14.3% (1/ 7) for IQC for CD4 counting. None of
      the nine laboratories which conducted QC for reagents used for rapid tests and
      none of the five which performed IQC and EQC had SOPs. HIV kits were mainly
      procured by the Medical Store Department and most of laboratories were not
      satisfied with the delay in procurement procedures. Most of the laboratories used
      rapid tests only, while some used both rapid tests and ELISA method for HIV
      testing. In conclusion, the survey revealed inadequacy in Good Laboratory
      Practice and poor laboratory quality control process for HIV testing reagents,
      internal and external quality control.

PMID- 17547101
TI  - Prevalence and determinants of cigarette smoking among adolescents in Blantyre
      City, Malawi.
AB  - Tobacco smoking is a major risk factor for non-communicable diseases such as
      ischaemic heart disease, stroke, chronic obstructive airways disease and several
      cancers. There is little data about the prevalence and determinants of smoking
      among adolescents in southern Africa. This study aimed to determine the
      prevalence and determinants of cigarette smoking among adolescents in Blantyre
      City, Malawi. Cross-sectional data were obtained from school-going adolescents in
      Blantyre in 2001 using the Global Youth Tobacco Survey data collection
      instrument. Data were analysed to determine prevalence of current and ever
      cigarette smoking, and predictors of smoking. The prevalence of current smoking
      and ever smoking were 3.0% and 15.6%, respectively. Predictors of current tobacco
      smoking included male gender, having friends or parents who smoked, having been
      exposed to advertisements about tobacco brands on television and having seen a
      lot of advertisements in newspapers and magazines. School programmes that
      included being taught about smoking in class and a class discussion on the
      dangers of tobacco were not associated with reduced current smoking. Intervention
      programmes aiming to curb tobacco smoking among adolescents should focus on
      dealing also with parental smoking, peer influence and pay special attention
      toward male gender. School-based programmes to prevent smoking should be
      evaluated as some may have little impact in influencing current smoking status.

PMID- 17547102
TI  - The prevalence of occupational asthma and rhinitis among woodworkers in south
      eastern Nigeria.
AB  - Wood dusts are known to cause respiratory disorders like rhinitis and asthma.
      This study was therefore done to determine the magnitude of the problem among
      woodworkers in south-eastern Nigeria exposed to high level of wood dust. Five
      hundred and ninety one woodworkers were selected using a stratified random
      sampling. The prevalence of woodwork-related rhinitis and asthma were then
      observed in the study population. Also the peak expiratory flow rate (PEFR) of
      each woodworker was obtained. The prevalence of occupational rhinitis was 78%,
      while that of asthma was 6.5%. As period of woodwork increased the prevalence of
      rhinitis and asthma increased (rhinitis: chi2 trend = 53.015, df = 1, P = 0.000).
      For asthma, chi2 trend = 19.721, df = 1, P = 0.000). Also the PEFR significantly
      became low with increasing years of exposure to woodwork (chi2 trend = 75.965, df
      = 1, P = 0.000). In conclusion the prevalence of rhinitis and asthma in
      woodworkers was high and significantly increased with years of working as a
      woodworker.

PMID- 17547103
TI  - The quality of water in small community supplies of Kingolwira village, Morogoro,
      Tanzania.
AB  - Water quality is an important aspect in human health, as the majority of
      infectious diseases that cause morbidity and mortality in population are water
      related. The present study was undertaken to assess the quality of water in
      Kingolwira, Morogoro Rural District, Tanzania. Water was collected from different
      sites in the village and analysed for a period of six months. Physical, chemical
      and microbiological qualities of water were examined. The pH of the water ranged
      from 7.02 to 7.20 and the water temperature ranged from 25.7 degrees C to 27.0
      degrees C. The total dissolved solids of the water samples ranged from 110 to 510
      ppm. The water contained considerable levels of lead and copper ranging from
      0.034 to 0.090 ppm and 0.022 to 0.030 ppm, respectively. Total water hardness
      ranged from 19.60 to 228.10 ppm as calcium carbonate. The total viable counts and
      faecal coliform counts ranged from 2.75 x 10(3) to 5.4 x 10(3) c.f.u/ml and 0.93
      x 10(2) to 2.1 x 10(2) counts/100ml, respectively. Overall, water supplies in the
      village were judged as of poor quality. Water is usually used for domestic
      purposes including cooking, drinking, washing and preparation of infant foods
      without any treatment. In conclusion therefore, water in Kingolwira village is of
      poor quality and needs to be treated before consumption. Theres is also a need
      for the rural population to be educated on hazards of using untreated water. In
      general, sanitary facilities in rural areas in Tanzania need to be improved in
      order to avoid health hazards.

PMID- 17547104
TI  - Lost investment returns from the migration of medical doctors from Malawi.
AB  - Migration of medical doctors from African countries to developed nations
      compromises the delivery of health care on the continent. The full cost of
      producing a medical doctor was estimated in Malawi by adding the costs of
      education from primary school through undergraduate medical education. The cost
      in fees for one medical doctor produced was US$ 56,946.79. The amount of lost
      investment returns for a doctor who migrated out and served for 30 years in the
      receiving country ranged from about US$ 433,493 to US$46 million at interest
      rates 7% and 25%, respectively. Quantitative assessments of the estimated loss in
      investment allows for informed policy discussions and decisions.

PMID- 17547105
TI  - [Metabolic syndrome: pathogenesis, future studies].

PMID- 17547106
TI  - [Insulin resistance as the basis of metabolic syndrome].

PMID- 17547107
TI  - [Hepatic lesions at insulin resistance].

PMID- 17547108
TI  - [Genetic mechanisms of abdominal obesity].

PMID- 17547109
TI  - [Eating behavior types and eating behavior hormones in patients with metabolic
      syndrome].

PMID- 17547110
TI  - [Atherogenic dyslipidemia, non-alcohol steatohepatitis, methods of treatment].

PMID- 17547111
TI  - [Sandpaper gallbladder and atherogenic dyslipidemia: a chain of successive
      events].

PMID- 17547112
TI  - [Pleiotropic effects of fibric acid derivatives (Lipanthyl-200) among patients
      with metabolic syndrome].

PMID- 17547113
TI  - [Particular features of the clinical course of gastroesophageal reflux disease in
      patients suffering from obesity].

PMID- 17547114
TI  - [Treatment of arterial hypertension with the use of trandolapril for patients
      with metabolic syndrome].

PMID- 17547115
TI  - [Non-steroid gastropathy: particular features of treatment].

PMID- 17547116
TI  - [Experience of treatment of patients with gastropathy induced by non-steroid anti
      inflammatory drugs].
AB  - A complex study of 147 patients who were taking non-steroid anti-inflammatory
      drugs (NSAIDs) revealed gastric lesions in 120 patients (81.6%). H2 blocker
      (ranitidine) was used for treating 40 patients with NSAID-induced gastropathy,
      proton pump inhibitor (omeprazole) was used for 40 patients, and Gastrozepin
      combined with Misoprostol--for 40 patients. Pain syndrome and dyspepsia were
      eliminated in most of the patients as a result of the treatment. Using
      Gastrozepin and Misoprostol produced an active effect on the trophic processes in
      the gastric mucous coat and caused erosion and ulcer healing. As compared to
      ranitidine and omeprazole, Gastrozepin used in combination with Cytotec produces
      a lower effect on the reduction of the acid-producing stomach function, yet it
      has a considerably greater effect on the normalization of the gastric mucus
      structure and restoration of metabolism of the gastric mucous coat collagen.

PMID- 17547117
TI  - [Non-steroid gastropathy combined with Helicobacter pylori: current problems].

PMID- 17547118
TI  - [Particular features of the clinical course of ulcer in tobacco farmers from
      Kyrgyzstan].
AB  - The article describes the results of the dispensary follow-up of patients with
      stomach and duodenal ulcers residing in tobacco farming districts in Osh Region
      (Kyrgyzstan). It turned out that tobacco farmers suffer from ulcers more
      frequently with a more severe course of the disease and various complications.
      Young farmers suffer from ulcers more frequently.

PMID- 17547119
TI  - Psychologic versus somatic? Is it a pertinent alternative?

PMID- 17547120
TI  - Clinical findings and psychosocial factors in patients with atypical odontalgia:
      a case-control study.
AB  - AIM: To provide a systematic description of clinical findings and psychosocial
      factors in patients suffering from atypical odontalgia (AO). METHODS: Forty-six
      consecutive AO patients (7 men and 39 women; mean age, 56 years; range, 31 to 81
      years) were compared with 35 control subjects (11 men and 24 women; mean age, 59
      years; range, 31 to 79 years). RESULTS: The pain of the AO patients was
      characterized by persistent, moderate pain intensity (mean, 5.6 +/- 1.9) with
      long pain duration (mean, 7.7 +/- 7.8 years). Eighty-three percent reported that
      onset of pain occurred in conjunction with dental treatment. No significant
      difference was found between the groups in number of remaining teeth or number of
      root fillings. Temporomandibular disorder (TMD) pain (P < .001), tension-type
      headache (P < .002), and widespread pain (P < .001) were significantly more
      common among AO patients than controls. Significantly higher scores for
      somatization (P < .01) and depression (P < .01) and limitations in jaw function
      (P < .001) were found for the AO group compared with the control group.
      Significant differences between groups were found in 4 general health domains:
      role-physical (P < .001), bodily pain (P < .001), vitality (P < .004), and social
      functioning (P < .001). CONCLUSION: A majority of the AO patients reported
      persistent, moderately intense intraoral pain that in most cases had an onset in
      conjunction with dental treatment. AO patients had more comorbid pain conditions
      and higher scores for depression and somatization. Significant limitation in jaw
      function and significantly lower scores on quality of life measures were found
      for AO patients compared with controls.

PMID- 17547121
TI  - Pain and pain-related interference associated with recurrent aphthous ulcers.
AB  - AIMS: (1) To use psychometrically sound measures to characterize the pain levels
      and pain-related interference associated with recurrent aphthous ulcers (RAU);
      (2) to determine whether subjects with RAU report clinically significant
      psychologic symptoms; and (3) to examine the relationships between physical
      characteristics and self-reported psychologic symptoms, pain, and pain-related
      interference. METHODS: Forty-seven subjects with RAU and an active ulcer
      completed the Graded Chronic Pain Scale and the Symptom Checklist-90R (SCL-90R).
      Ulcers were photographed for measurement, and subjects rated pain levels on a 0
      to-l0 scale before and after swabbing of the ulcer with a saturated solution of
      sodium chloride and distilled water. RESULTS: Mean characteristic pain intensity
      was 4.76, with a pain-related interference score of 1.21. None of the average SCL
      90R subscale scores were considered elevated. In the model predicting pain
      intensity after swabbing, pain intensity before swabbing explained 43.6% of the
      variance (P = .000). Neither the addition of physical characteristics (R2 change
      = .04; P = .28) nor psychologic characteristics (R2 change = .09; P = .83)
      contributed significantly to the model. In contrast, only psychologic
      characteristics contributed to the variance explained in the model predicting
      pain-related interference (R2 change = .505; P = .007). CONCLUSIONS: RAU is a
      moderately painful condition causing some impairment in functioning. Self
      reported pain intensity of a sore does not appear to be influenced by psychologic
      characteristics. However, pain-related interference appears to be related to
      psychologic and not physical characteristics.

PMID- 17547122
TI  - Prevalence and impact of post-traumatic stress disorder symptoms in patients with
      masticatory muscle or temporomandibular joint pain: differences and similarities.
AB  - AIMS: To evaluate temporomandibular disorder (TMD) patients for differences
      between masticatory muscle (MM) and temporomandibular joint (TMJ) pain patients
      in the prevalence of posttraumatic stress disorder (PTSD) symptoms and evaluate
      the level of psychological dysfunction and its relationship to PTSD symptoms in
      these patients. METHODS: This study included 445 patients. Psychological
      questionnaires included the Symptom Check List-90-Revised (SCL-90-R), the
      Multidimensional Pain Inventory, the Pittsburgh Sleep Quality Index, and the PTSD
      Check List Civilian. The total sample of patients was divided into 2 major
      groups: the MM group (n = 242) and the TMJ group (n = 203). Each group was
      divided into 3 subgroups based on the presence of a stressor and severity of PTSD
      symptoms. RESULTS: Thirty-six patients (14.9%) in the MM group and 20 patients
      (9.9%) in the TMJ group presented with PTSD symptomatology (P = .112).
      Significant differences were found between the MM and the TMJ group in several
      psychometric domains, but when the presence of PTSD symptomatology was
      considered, significant differences were mostly maintained in the subgroups
      without PTSD. MM and TMJ pain patients in the "positive PTSD" subgroups scored
      higher on all SCL-90-R scales (P < .001) than patients in the other 2 subgroups
      and reached levels of distress indicative of psychological dysfunction. TMJ pain
      patients (58.3%; P = .008) in the positive-PTSD subgroups were more often
      classified as dysfunctional. Both positive-PTSD subgrounps of the MM and TMJ
      groups presented with more sleep disturbance (P < .005) than patients in the
      other 2 subgroups. CONCLUSION: A somewhat elevated prevalence rate for PTSD
      symptomatology was found in the MM group compared to the TMJ group. Significant
      levels of psychological dysfunction appeared to be linked to TMD patients with
      PTSD symptoms.

PMID- 17547123
TI  - Juvenile arthritis and development of symptoms of temporomandibular disorders: a
      15-year prospective cohort study.
AB  - AIMS: To compare the development of symptoms of temporomandibular disorders (TMD)
      in a sample of patients with juvenile arthritis (JA) and a matched control
      sample. METHODS: In 1986, 40 patients with JA (28 girls and 12 boys; mean age +/-
      SD, 18 +/- 4.5 years) and an age- and sex-matched control sample were examined
      for signs and symptoms of TMD. Fifteen years later in 2001, a questionnaire
      concerning symptoms of TMD was sent to these subjects. Twenty-eight individuals
      (68%) in the JA sample (20 women and 8 men; mean age +/- SD, 35 +/- 5.2 years)
      and 26 controls (19 women and 7 men; 34 +/- 4.0 years) were available for the
      follow-up. RESULTS: The overall prevalence of symptoms of TMD increased between
      the 2 examinations in both groups. The prevalence of reported TMD symptoms, such
      as jaw pain, fatigue in the jaws, and difficulty opening the jaws wide, as well
      as awareness of tooth clenching, headaches, neck and shoulder pains, was
      significantly greater among the JA sample than among the controls at the follow
      up. CONCLUSION: The study indicates that prevalence of pain and dysfunction in
      the craniofacial or cervical regions of JA patients is increased more than 20
      years after the onset of JA compared to healthy individuals.

PMID- 17547124
TI  - Incidence and temporal patterns of temporomandibular disorder pain among Swedish
      adolescents.
AB  - AIMS: To estimate the incidence of temporomandibular disorder (TMD) pain among
      Swedish adolescents by age and gender and to describe the temporal patterns of
      TMD pain. METHODS: This 3-year longitudinal study was carried out at all Public
      Dental Service clinics in a Swedish county from 2000 to 2003. All individuals
      aged 12 to 19 years in the county who visited the clinics for annual examinations
      were eligible for the study. RESULTS: Overall, the incidence of TMD pain among
      all adolescents was 2.9% annually among 2,255 participating adolescents.
      Incidence among girls was significantly higher than in boys, 4.5% versus 1.3%,
      respectively. Incidence increased with age in girls and boys, although less so in
      boys (3.0% to 6.9% versus 1.7% to 2.6%). These adolescents were re-examined
      annually for 3 years, and a fluctuating pattern of TMD pain was common. Overall,
      11.4% of all subjects reported TMD pain on at least 1 occasion; 88.6% of the
      cohort remained pain-free. Of those reporting TMD pain, 4.7% could be defined as
      intermittent cases, 3.1% were single-incident cases, 0.9% were recurrent cases,
      and 0.9% had continuing pain for 1 or 2 years. CONCLUSION: The incidence of self
      reported TMD pain among Swedish adolescents aged 12 to 19 years increased with
      age, particularly among girls. The pattern of pain in most adolescents fluctuated
      over time. Less than 1% of the cohort had continued pain over each year, and the
      majority of these subjects were girls.

PMID- 17547125
TI  - Intra- and interrater agreement of pressure pain threshold for masticatory
      structures in children reporting orofacial pain related to temporomandibular
      disorders and symptom-free children.
AB  - AIMS: To determine intra- and interrater agreement of the pressure pain threshold
      (PPT) values for children reporting orofacial pain related to temporomadibular
      disorders and symptom-free subjects when the mean of 3 consecutive measurements
      or the mean of the last 2 consecutive measurements was considered. METHODS:
      Fourteen children reporting pain in masticatory muscles or the temporomandibular
      joint and 16 symptom-free children were selected at random from a sample of 100
      children. Two trained raters used an algometer to obtain 3 consecutive
      measurements of PPT of the masticatory system sites. The children were evaluated
      in 3 sessions after a minimum period of 3 days after the initial evaluation. The
      intraclass correlation coefficient (ICC) was used to evaluate the levels of
      agreement. RESULTS: Excellent intra- and interrater agreement was observed (ICC >
      0.75) for most of the structures evaluated in symptom-free children, and
      excellent and moderate agreement was obtained for the symptomatic group.
      Discarding the first of the 3 measurements increased the number of sites with ICC
      values classified as excellent in both groups. For evaluations performed on
      different days, this procedure reduced significantly the percentage of sites with
      ICC values classified as excellent only for the interrater agreement for the
      symptomatic group. CONCLUSION: The lower levels of reproducibility for the
      measurements obtained on different days in the children who reported pain may
      have been related to instability of their clinical signs and symptoms, and a PPT
      assessment based on the mean of 3 consecutive measurements or the procedure of
      discarding the first measure should be considered for such evaluations,
      especially when they are conducted by different raters. Algometry was shown to be
      a reliable tool for the evaluation of pain threshold in the masticatory
      structures of children.

PMID- 17547126
TI  - Low bone mineral density and temporomandibular joint derangement in young
      females.
AB  - AIMS: To analyze the bone mineral density (BMD) in a group of young female
      patients with a disc displacement in at least 1 temporomandibular joint (TMJ) as
      well as in a group of age-matched young females with a normal condyle-disc
      relationship. METHODS: Fifty-six young female patients with anterior disc
      displacement based on magnetic resonance imaging (MRI) and 40 age- and gender
      matched controls with asymptomatic TMJs were recruited for this study. Subjects
      between 18 and 30 years were recruited. Based on the MRI findings, 10 of the 40
      subjects in the control group also had anterior disc displacement. In all, 16
      subjects had an anterior disc displacement with reduction (DDwR), 50 had an
      anterior disc displacement without reduction (DDw/oR), and 30 had a normal
      condyle-disc relationship. BMD was measured in the lumbar area by means of dual
      energy x-ray absorptiometry. The relationship between the 3 types of condyle-disc
      relationship and BMD was then analyzed. RESULTS: Patients with a DDw/oR had a
      significantly lower mean BMD value in the lumbar area than the subjects with a
      normal condyle-disc relationship (P < .05, analysis of variance, post-hoc with
      Bonferroni test). Twenty-two (44%) of 50 patients with DDw/oR had osteopenia.
      CONCLUSION: Low BMD is often associated with DDw/oR in young Taiwanese female
      patients.

PMID- 17547127
TI  - Orofacial pain, where are we? Scientific meeting of the European Academy of
      Craniomandibular Disorders and the Spanish Society of Craniomandibular Disorders
      and Orofacial Pain September 28 to October 1, 2006, Barcelona, Spain.

PMID- 17547128
TI  - An image morphing technique based on optimal mass preserving mapping.
AB  - Image morphing, or image interpolation in the time domain, deals with the
      metamorphosis of one image into another. In this paper, a new class of image
      morphing algorithms is proposed based on the theory of optimal mass transport.
      The L(2) mass moving energy functional is modified by adding an intensity
      penalizing term, in order to reduce the undesired double exposure effect. It is
      an intensity-based approach and, thus, is parameter free. The optimal warping
      function is computed using an iterative gradient descent approach. This proposed
      morphing method is also extended to doubly connected domains using a harmonic
      parameterization technique, along with finite-element methods.

PMID- 17547129
TI  - The error-amended sharp edge (EASE) scheme for image zooming.
AB  - This paper proposes a new interpolation method, called the error-amended sharp
      edge (EASE) scheme, which is a modified bilinear method. In order to
      remove/reduce interpolation artifacts such as image blur and the checkerboard
      effect (ringing), EASE tries to amend the interpolation error by employing the
      classical interpolation error theorem in an edge-adaptive fashion. EASE is
      applied for image zooming by both integer and noninteger magnification factors.
      The new interpolation scheme has proved to result in high-resolution images
      having clearer and sharper edges than linear interpolation methods, for all
      synthetic and natural images we have tested. EASE can be implemented with ease;
      it turns out to be similarly efficient as cubic interpolation schemes.

PMID- 17547130
TI  - Algebraic signal processing theory: 2-D spatial hexagonal lattice.
AB  - We develop the framework for signal processing on a spatial, or undirected, 2-D
      hexagonal lattice for both an infinite and a finite array of signal samples. This
      framework includes the proper notions of z-transform, boundary conditions,
      filtering or convolution, spectrum, frequency response, and Fourier transform. In
      the finite case, the Fourier transform is called discrete triangle transform.
      Like the hexagonal lattice, this transform is nonseparable. The derivation of the
      framework makes it a natural extension of the algebraic signal processing theory
      that we recently introduced. Namely, we construct the proper signal models, given
      by polynomial algebras, bottom-up from a suitable definition of hexagonal space
      shifts using a procedure provided by the algebraic theory. These signal models,
      in turn, then provide all the basic signal processing concepts. The framework
      developed in this paper is related to Mersereau's early work on hexagonal
      lattices in the same way as the discrete cosine and sine transforms are related
      to the discrete Fourier transform-a fact that will be made rigorous in this
      paper.

PMID- 17547131
TI  - Hyperanalytic denoising.
AB  - A new threshold rule for the estimation of a deterministic image immersed in
      noise is proposed. The full estimation procedure is based on a separable wavelet
      decomposition of the observed image, and the estimation is improved by
      introducing the new threshold to estimate the decomposition coefficients. The
      observed wavelet coefficients are thresholded, using the magnitudes of wavelet
      transforms of a small number of "replicates" of the image. The "replicates" are
      calculated by extending the image into a vector-valued hyperanalytic signal. More
      than one hyperanalytic signal may be chosen, and either the hypercomplex or Riesz
      transforms are used, to calculate this object. The deterministic and stochastic
      properties of the observed wavelet coefficients of the hyperanalytic signal, at a
      fixed scale and position index, are determined. A "universal" threshold is
      calculated for the proposed procedure. An expression for the risk of an
      individual coefficient is derived. The risk is calculated explicitly when the
      "universal" threshold is used and is shown to be less than the risk of
      "universal" hard thresholding, under certain conditions. The proposed method is
      implemented and the derived theoretical risk reductions substantiated.

PMID- 17547132
TI  - Fast planar-oriented ripple search algorithm for hyperspace VQ codebook.
AB  - This paper presents a fast codebook search method for improving the quantization
      complexity of full-search vector quantization (VQ). The proposed method is built
      on the planar Voronoi diagram to label a ripple search domain. Then, the
      appropriate codeword can easily be found just by searching the local region
      instead of global exploration. In order to take a step further and obtain the
      close result full-search VQ would, we equip the proposed method with a
      duplication mechanism that helps to bring down the possible quantizing distortion
      to its lowest level. According to the experimental results, the proposed method
      is indeed capable of providing better outcome at a faster quantization speed than
      the existing partial-search methods. Moreover, the proposed method only requires
      a little extra storage for duplication.

PMID- 17547133
TI  - Histogram approaches for lossy compression of digital holograms of three
      dimensional objects.
AB  - We present a novel nonuniform quantization compression technique-histogram
      quantization-for digital holograms of 3-D real-world objects. We exploit a priori
      knowledge of the distribution of the values in our data. We compare this
      technique to another histogram based approach: a modified version of Max's
      algorithm that has been adapted in a straight-forward manner to complex-valued 2
      D signals. We conclude the compression procedure by applying lossless techniques
      to our quantized data. We demonstrate improvements over previous results obtained
      by applying uniform and nonuniform quantization techniques to the hologram data.

PMID- 17547134
TI  - Iterative decoding of serially concatenated arithmetic and channel codes with
      JPEG 2000 applications.
AB  - In this paper, an innovative joint-source channel coding scheme is presented. The
      proposed approach enables iterative soft decoding of arithmetic codes by means of
      a soft-in soft- out decoder based on suboptimal search and pruning of a binary
      tree. An error-resilient arithmetic coder with a forbidden symbol is used in
      order to improve the performance of the joint source/channel scheme. The
      performance in the case of transmission across the AWGN channel is evaluated in
      terms of word error probability and compared to a traditional separated approach.
      The interleaver gain, the convergence property of the system, and the optimal
      source/channel rate allocation are investigated. Finally, the practical relevance
      of the proposed joint decoding approach is demonstrated within the JPEG 2000
      coding standard. In particular, an iterative channel and JPEG 2000 decoder is
      designed and tested in the case of image transmission across the AWGN channel.

PMID- 17547135
TI  - Joint source-channel coding using real BCH codes for robust image transmission.
AB  - In this paper, a new still image coding scheme is presented. In contrast with
      standard tandem coding schemes, where the redundancy is introduced after source
      coding, it is introduced before source coding using real BCH codes. A joint
      channel model is first presented. The model corresponds to a memoryless mixture
      of Gaussian and Bernoulli-Gaussian noise. It may represent the source coder, the
      channel coder, the physical channel, and their corresponding decoder. Decoding
      algorithms are derived from this channel model and compared to a state-of-art
      real BCH decoding scheme. A further comparison with two reference tandem coding
      schemes and the proposed joint coding scheme for the robust transmission of still
      images has been presented. When the tandem scheme is not accurately tuned, the
      joint coding scheme outperforms the tandem scheme in all situations. Compared to
      a tandem scheme well tuned for a given channel situation, the joint coding scheme
      shows an increased robustness as the channel conditions worsen. The soft
      performance degradation observed when the channel worsens gives an additional
      advantage to the joint source-channel coding scheme for fading channels, since a
      reconstruction with moderate quality may be still possible, even if the channel
      is in a deep fade.

PMID- 17547136
TI  - Detecting wide lines using isotropic nonlinear filtering.
AB  - Lines provide important information in images, and line detection is crucial in
      many applications. However, most of the existing algorithms focus only on the
      extraction of line positions, ignoring line thickness. This paper presents a
      novel wide line detector using an isotropic nonlinear filter. Unlike most
      existing edge and line detectors which use directional derivatives, our proposed
      wide line detector applies a nonlinear filter to extract a line completely
      without any derivative. The detector is based on the isotropic responses via
      circular masks. A general scheme for the analysis of the robustness of the
      proposed wide line detector is introduced and the dynamic selection of parameters
      is developed. In addition, this paper investigates the relationship between the
      size of circular masks and the width of detected lines. A sequence of tests has
      been conducted on a variety of image samples and our experimental results
      demonstrate the feasibility and effectiveness of the proposed method.

PMID- 17547137
TI  - Image superresolution using support vector regression.
AB  - A thorough investigation of the application of support vector regression (SVR) to
      the superresolution problem is conducted through various frameworks. Prior to the
      study, the SVR problem is enhanced by finding the optimal kernel. This is done by
      formulating the kernel learning problem in SVR form as a convex optimization
      problem, specifically a semi-definite programming (SDP) problem. An additional
      constraint is added to reduce the SDP to a quadratically constrained quadratic
      programming (QCQP) problem. After this optimization, investigation of the
      relevancy of SVR to superresolution proceeds with the possibility of using a
      single and general support vector regression for all image content, and the
      results are impressive for small training sets. This idea is improved upon by
      observing structural properties in the discrete cosine transform (DCT) domain to
      aid in learning the regression. Further improvement involves a combination of
      classification and SVR-based techniques, extending works in resolution synthesis.
      This method, termed kernel resolution synthesis, uses specific regressors for
      isolated image content to describe the domain through a partitioned look of the
      vector space, thereby yielding good results.

PMID- 17547138
TI  - A hybrid algorithm with artifact detection mechanism for region filling after
      object removal from a digital photograph.
AB  - This work aims to develop a novel function of the digital camera, i.e., region
      filling after object removal from a digital photograph. This problem is defined
      as how to "guess" the Lacuna region after removal of an object by replicating a
      part from the remainder of the whole image with visually plausible quality. We
      propose a hybrid region-filling algorithm composed of a texture synthesis
      technique and an efficient interpolation method with a refinement approach: 1)
      the "subpatch texture synthesis technique" can synthesize the Lacuna region with
      significant accuracy; 2) the "weighted interpolation method" is applied to reduce
      computaion time; and 3) the "artifact detection mechanism" integrates the Kirsch
      edge detector and color ratio gradients to detect the artifact blocks in the
      filled region after the first pass of filling the Lacuna region when the result
      may not be satisfactory. This can lead to resynthesizing the artifact blocks
      without user intervention and can be compliant to the unsuccessful results of
      other algorithms. In the procedure of region-filling, color texture distribution
      analysis is used to choose whether the subpatch texture synthesis technique or
      the weighted interpolation method should be applied. In the subpatch texture
      synthesis technique, the actual pixel values of the Lacuna region are synthesized
      by adaptively sampling from the source region. The experimental results show that
      our proposed algorithm can achieve a better performance than previous methods.
      Particularly, the regular computation of our proposed algorithm is more suitable
      for implementation of the hardware in a digital camera.

PMID- 17547139
TI  - The equivalence of half-quadratic minimization and the gradient linearization
      iteration.
AB  - A popular way to restore images comprising edges is to minimize a cost function
      combining a quadratic data-fidelity term and an edge-preserving (possibly
      nonconvex) regularizalion term. Mainly because of the latter term, the
      calculation of the solution is slow and cumbersome. Half-quadratic (HQ)
      minimization (multiplicative form) was pioneered by Geman and Reynolds (1992) in
      order to alleviate the computational task in the context of image reconstruction
      with nonconvex regularization. By promoting the idea of locally homogeneous image
      models with a continuous-valued line process, they reformulated the optimization
      problem in terms of an augmented cost function which is quadratic with respect to
      the image and separable with respect to the line process, hence the name "half
      quadratic." Since then, a large amount of papers were dedicated to HQ
      minimization and important results--including edge-preservation along with convex
      regularization and convergence-have been obtained. In this paper, we show that HQ
      minimization (multiplicative form) is equivalent to the most simple and basic
      method where the gradient of the cost function is linearized at each iteration
      step. In fact, both methods give exactly the same iterations. Furthermore,
      connections of HQ minimization with other methods, such as the quasi-Newton
      method and the generalized Weiszfeld's method, are straightforward.

PMID- 17547140
TI  - A short- time beltrami kernel for smoothing images and manifolds.
AB  - We introduce a short-time kernel for the Beltrami image enhancing flow. The flow
      is implemented by "convolving" the image with a space dependent kernel in a
      similar fashion to the solution of the heat equation by a convolution with a
      Gaussian kernel. The kernel is appropriate for smoothing regular (flat) 2-D
      images, for smoothing images painted on manifolds, and for simultaneously
      smoothing images and the manifolds they are painted on. The kernel combines the
      geometry of the image and that of the manifold into one metric tensor, thus
      enabling a natural unified approach for the manipulation of both. Additionally,
      the derivation of the kernel gives a better geometrical understanding of the
      Beltrami flow and shows that the bilateral filter is a Euclidean approximation of
      it. On a practical level, the use of the kernel allows arbitrarily large time
      steps as opposed to the existing explicit numerical schemes for the Beltrami
      flow. In addition, the kernel works with equal ease on regular 2-D images and on
      images painted on parametric or triangulated manifolds. We demonstrate the
      denoising properties of the kernel by applying it to various types of images and
      manifolds.

PMID- 17547141
TI  - Ultrasound image segmentation with shape priors: application to automatic cattle
      rib-eye area estimation.
AB  - Automatic ultrasound (US) image segmentation is a difficult task due to the
      quantity of noise present in the images and the lack of information in several
      zones produced by the acquisition conditions. In this paper, we propose a method
      that combines shape priors and image information to achieve this task. In
      particular, we introduce knowledge about the rib-eye shape using a set of images
      manually segmented by experts. A method is proposed for the automatic
      segmentation of new samples in which a closed curve is fitted taking into account
      both the US image information and the geodesic distance between the evolving
      curve and the estimated mean rib-eye shape in a shape space. This method can be
      used to solve similar problems that arise when dealing with US images in other
      fields. The method was successfully tested over a database composed of 610 US
      images, for which we have the manual segmentations of two experts.

PMID- 17547142
TI  - Learning and matching of dynamic shape manifolds for human action recognition.
AB  - In this paper, we learn explicit representations for dynamic shape manifolds of
      moving humans for the task of action recognition. We exploit locality preserving
      projections (LPP) for dimensionality reduction, leading to a low-dimensional
      embedding of human movements. Given a sequence of moving silhouettes associated
      to an action video, by LPP, we project them into a low-dimensional space to
      characterize the spatiotemporal property of the action, as well as to preserve
      much of the geometric structure. To match the embedded action trajectories, the
      median Hausdorff distance or normalized spatiotemporal correlation is used for
      similarity measures. Action classification is then achieved in a nearest-neighbor
      framework. To evaluate the proposed method, extensive experiments have been
      carried out on a recent dataset including ten actions performed by nine different
      subjects. The experimental results show that the proposed method is able to not
      only recognize human actions effectively, but also considerably tolerate some
      challenging conditions, e.g., partial occlusion, low-quality videos, changes in
      viewpoints, scales, and clothes; within-class variations caused by different
      subjects with different physical build; styles of motion; etc.

PMID- 17547143
TI  - Incremental kernel principal component analysis.
AB  - The kernel principal component analysis (KPCA) has been applied in numerous image
      related machine learning applications and it has exhibited superior performance
      over previous approaches, such as PCA. However, the standard implementation of
      KPCA scales badly with the problem size, making computations for large problems
      infeasible. Also, the "batch" nature of the standard KPCA computation method does
      not allow for applications that require online processing. This has somewhat
      restricted the domains in which KPCA can potentially be applied. This paper
      introduces an incremental computation algorithm for KPCA to address these two
      problems. The basis of the proposed solution lies in computing incremental linear
      PCA in the kernel induced feature space, and constructing reduced-set expansions
      to maintain constant update speed and memory usage. We also provide experimental
      results which demonstrate the effectiveness of the approach.

PMID- 17547144
TI  - Joint source and channel coding for 3-D scene databases using vector quantization
      and embedded parity objects.
AB  - Three-dimensional graphic scenes contain various mesh objects in one geometric
      space where different objects have potentially unequal importance regarding
      display. This paper proposes an object-oriented system for efficiently coding and
      streaming 3-D scene databases in lossy and rate-constrained environments. Vector
      quantization (VQ) is exploited to code 3-D scene databases into multiresolution
      hierarchies. For the best distortion-rate performance, adaptive quantization
      precisions are allocated to different objects and different layers of each object
      based on a weighted distortion model. Upon transmission, scalably coded objects
      are delivered in respective packet sequences to preserve their manipulation
      independency. For packet loss resilience, a plurality of FEC codes are generated
      as "parity objects" parallel to graphic objects, which protect the graphic
      objects concurrently and also preferentially in regard to their unequal decoding
      importance. A rate-distortion optimization framework is then developed, which
      performs rate allocation between graphic objects and parity objects and generates
      the parity data properly. We show that, by treating graphic objects jointly and
      preferentially in source and channel coding while preserving their independencies
      in transport, the proposed system reduces the receiving distortion of the 3-D
      database significantly compared to conventional methods.

PMID- 17547145
TI  - Reversible integer color transform.
AB  - In this correspondence, we introduce a systematic algorithm that can convert any
      3 x 3 color transform into a reversible integer-to-integer transform. We also
      discuss the ways to improve accuracy and reduce implementation complexity. We
      derive the integer RGB-to-KLA, IV1 V2, YCbCr, DCT, YUV, and YIQ transforms that
      are optimal in accuracy.

PMID- 17547146
TI  - Objective distortion measure for binary text image based on edge line segment
      similarity.
AB  - This paper proposes a new approach to measure the distortion introduced by
      changing individual edge pixels in binary text images. The approach considers not
      only how many pixels are changed but also where the pixels are changed and how
      the flipping affects the overall shape formed by the edge line. Similarities
      between the edge line segments in the original and distorted image are compared
      to measure the distortion. Subjective testing shows that the new distortion
      measure correlates well with human visual perception.

PMID- 17547147
TI  - Snow shows perfluorochemical source.

PMID- 17547148
TI  - New Jersey dives into PFOA water guidance.

PMID- 17547149
TI  - Pricing tomorrow's coal-fired power plant.

PMID- 17547150
TI  - Bush expands influence over regulations.

PMID- 17547151
TI  - Sharing sustainable solutions.

PMID- 17547152
TI  - A potential new Crypto source.

PMID- 17547153
TI  - Aerosolized contaminants from biosolids.

PMID- 17547154
TI  - A heavy-metal history in Peru.

PMID- 17547155
TI  - Drugs, pesticides, and politics--a potent mix in Colombia.

PMID- 17547156
TI  - Pesticides in U.S. streams and groundwater.

PMID- 17547157
TI  - Integrating developed and developing world knowledge into global discussions and
      strategies for sustainability. 1. Science and technology.
AB  - Sustainable development in both the developed and developing world has the common
      fundamental themes of advancing economic and social prosperity while protecting
      and restoring natural systems. While many recent efforts have been undertaken to
      transfer knowledge from the developed to the developing world to achieve a more
      sustainable future, indigenous knowledge that often originates in developing
      nations also can contribute significantly to this global dialogue. Selected case
      studies are presented to describe important knowledge, methodologies, techniques,
      principles, and practices for sustainable development emerging from developing
      countries in two critical challenge areas to sustainability: water and energy.
      These, with additional analysis and quantification, can be adapted and expanded
      for transfer throughout the developed and developing world in advancing
      sustainability. A common theme in all of the case studies presented is the
      integration of natural processes and material flows into the anthropogenic
      system. Some of these techniques, originating in rural settings, have recently
      been adapted for use in cities, which is especially important as the global trend
      of urban population growth accelerates. Innovations in science and technology,
      specifically applied to two critical issues of today, water and energy, are
      expected to fundamentally shift the type and efficiency of energy and materials
      utilized to advance prosperity while protecting and restoring natural systems.

PMID- 17547158
TI  - Integrating developed and developing world knowledge into global discussions and
      strategies for sustainability. 2. Economics and governance.
AB  - Knowledge transfer from the developing to the developed world is described in the
      domain of economics and governance for sustainable development. Three system
      areas are explored: the structure of commons governance institutions, the process
      of community-based participatory action research, and the role of microfinance
      and microenterprise for the development, adoption, and diffusion of sustainable
      technologies. Case studies from both the developed and developing world
      demonstrate the effectiveness of social networks and community cooperative
      strategies in a wide range of sectors. Developing world experiences are shown to
      be particularly rich in the application of local knowledge and social capital
      toward sustainable development.

PMID- 17547159
TI  - Baseload coal investment decisions under uncertain carbon legislation.
AB  - More than 50% of electricity in the U.S. is generated by coal. The U.S. has large
      coal resources, the cheapest fuel in most areas. Coal fired power plants are
      likely to continue to provide much of U.S. electricity. However, the type of
      power plant that should be built is unclear. Technology can reduce pollutant
      discharges and capture and sequester the CO2 from coal-fired generation. The U.S.
      Energy Policy Act of 2005 provides incentives for large scale commercial
      deployment of Integrated Coal Gasification Combined Cycle (IGCC) systems (e.g.,
      loan guarantees and project tax credits). This analysis examines whether a new
      coal plant should be Pulverized Coal (PC) or IGCC. Do stricter emissions
      standards (PM, SO2, NOx, Hg) justify the higher costs of IGCC over PC? How does
      potential future carbon legislation affect the decision to add carbon capture and
      storage (CCS) technology? Finally, can the impact of uncertain carbon legislation
      be minimized? We find that SO2, NOx, PM, and Hg emission standards would have to
      be far more stringent than twice current standards to justify the increased costs
      of the IGCC system. A C02 tax less than $29/ton would lead companies to
      continuing to choose PC, paying the tax for emitted CO2. The earlier a decision
      maker believes the carbon tax will be imposed and the higher the tax, the more
      likely companies will choose IGCC w/CCS. Having government announce the date and
      level of a carbon tax would promote more sensible decisions, but government would
      have to use a tax or subsidy to induce companies to choose the technology that is
      best for society.

PMID- 17547160
TI  - Chemical quality of depositional sediments and associated soils in New Orleans
      and the Louisiana peninsula following Hurricane Katrina.
AB  - Hurricane Katrina made landfall on the Louisiana peninsula south of New Orleans
      on Aug 29, 2005. The resulting storm surge caused numerous levy breaches in the
      parishes of New Orleans as well as on the Louisiana peninsula. This study was
      conducted to determine the concentrations of inorganic and organic constituents
      in sediments and associated soils in New Orleans parishes and the Louisiana
      peninsula after the floodwaters had been removed and/or receded following
      Hurricane Katrina. A total of 46 sediment and soil samples were analyzed that
      were collected throughout New Orleans and the Louisiana peninsula. Approximately
      20% of the sediment samples were analyzed, including shallow sediment samples
      from locations that included the top and beneath automobiles, in residential and
      commercial areas, and near refineries. Gasoline constituents, pesticides, and
      leachable heavy metals were analyzed using headspace gas chromatography/mass
      spectrometry (GC/MS), organic extraction GC/MS, and inductively coupled
      plasma/mass spectrometry, respectively. A significant number of samples had
      leachable As and Pb concentrations in excess of drinking water standards. The
      remaining metals analyzed (i.e., Cd, Cr, Cu, Hg, and V) generally had much lower
      leachable levels. Of the gasoline constituents, only benzene was observed above
      the limit of detection (of 5 microg/kg), with no samples observed as being above
      the method detection limits of 10 microg/kg. For the 18 pesticides analyzed, most
      were in the nondetectable range and all were in trace amounts that were orders of
      magnitude below regulatory guidelines.

PMID- 17547161
TI  - Magnetic resonance imaging of the effect of zeolite on lithium uptake in poplar.
AB  - The use of a zeolite (clinoptilolite) to protect poplar plants from lithium
      contaminated soil has been studied using magnetic resonance imaging. Lithium was
      used as a model contaminant as it could be tracked directly using specific
      nuclear magnetic resonance probes, rather than relying on relaxation time effects
      on protons due to paramagnetic solutes. The sorption of lithium to the zeolite
      was investigated both in static and dynamic systems; lithium was found to sorb
      readily to the zeolite over time. Poplar plants were grown in soil microcosms
      consisting of either sand or sand and zeolite with nutrients provided through the
      use of Hoagland's solution as the pore fluid. Both one-dimensional profiles of
      lithium concentration along poplar stems and direct lithium imaging of stem cross
      sections were employed to reveal the uptake of the contaminant into the plant
      structure, showing significantly less lithium present in plants grown in sand and
      zeolite than those grown in sand alone. Evidence of structural features involved
      in the uptake of lithium was also obtained.

PMID- 17547162
TI  - Reflectance spectroscopy study of Cd contamination in the sediments of the
      Changjiang River, China.
AB  - Sediments of the Changjiang River have been found in recent studies to be
      enriched in cadmium (Cd). The possibility and mechanisms for evaluating total Cd
      concentration and its binding form using reflectance spectroscopy within the
      visible-near-infrared (VNIR) region (400-2500 nm) have been investigated. Bottom
      sediments (69 samples) in the lower reaches of the river were collected for
      chemical analyses and spectral measurements. Total Cd concentration in the
      sediments was found to be exponentially related to the spectral proxies for
      organic matter(spectral reflectance at 400-530 nm), clay minerals (first
      derivative (FD) values at the shoulders related to absorption bands near 1400,
      1900, and 2200 nm), and Fe oxides (FD values at 560-760 nm). The results
      indicated that the spectrally featureless Cd was mostly bound to these spectrally
      active materials, which made it possible for Cd concentration to be determined
      from reflectance spectra. This conclusion was also confirmed bythe results of
      chemically sequential extraction of Cd. This study has demonstrated the usage and
      theoretical basis of reflectance spectroscopy, which is a rapid and inexpensive
      analytical method, for evaluating contamination by heavy metals and their binding
      forms in sediments.

PMID- 17547163
TI  - Perfluorinated acids in Arctic snow: new evidence for atmospheric formation.
AB  - Perfluorinated acids (PFAs) are ubiquitously found in water and biota, including
      remote regions such as the High Arctic. Under environmental conditions, PFAs
      exist mainly as anions and are not expected to be subject to long-range
      atmospheric transport in the gas phase. Fluorinated telomer alcohols (FTOHs) are
      volatile and can be atmospherically oxidized to form perfluorocarboxylic acids.
      Analogously, fluorosulfamido alcohols can be oxidized to form perfluorooctane
      sulfonate (PFOS). High Arctic ice caps experience contamination solely from
      atmospheric sources. By examining concentrations of PFAs in ice cap samples, it
      is possible to determine atmospheric fluxes to the Arctic. Ice samples were
      collected from high Arctic ice caps in the spring of 2005 and 2006. Samples were
      concentrated using solid-phase extraction and analyzed by LC-MS-MS. PFAs were
      observed in all samples, dating from 1996 to 2005. Concentrations were in the low
      mid pg L(-1) range and exhibited seasonality, with maximum concentrations in the
      spring-summer. The presence of perfluorodecanoic acid (PFDA) and
      perfluoroundecanoic acid (PFUnA) on the ice cap was indicative of atmospheric
      oxidation as a source. Ratios of PFAs to sodium concentrations were highly
      variable, signifying PFA concentrations on the ice cap were unrelated to marine
      chemistry. Fluxes of the PFAs were estimated to the area north of 65 degrees N
      for the 2005 season, which ranged from 114 to 587 kg year(-1) for
      perfluorooctanoic acid (PFOA), 73 to 860 kg year(-1) for perfluorononanoic acid
      (PFNA), 16 to 84 kg year(-1) for PFDA, 26 to 62 kg year(-1) for PFUnA, and 18 to
      48 kg year(-1) for PFOS. The PFOA and PFNA fluxes agreed with FTOH modeling
      estimations. A decrease in PFOS concentrations through time was observed,
      suggesting a fast response to changes in production. These data suggest that
      atmospheric oxidation of volatile precursors is a primary source of PFAs to the
      Arctic.

PMID- 17547164
TI  - Occurrence of natural and synthetic glucocorticoids in sewage treatment plants
      and receiving river waters.
AB  - This paper first reports the occurrence of sixglucocorticoids (prednisone,
      prednisolone, cortisone, cortisol, dexamethasone, and 6alpha-methylprednisolone)
      in sewage treatment plants (STPs) and receiving rivers by establishing a method
      for analyzing glucocorticoids in complex environmental waters. For the various
      types of aqueous matrices considered, the absolute recoveries were from 73 to
      99%, and limits of quantification were below 0.2 ng/L. Among the seven STPs
      studied, the average concentrations of prednisone, prednisolone, cortisone,
      cortisol, dexamethasone, and 6alpha-methylprednisolone in influents were,
      respectively, 2.6 +/- 2.1, 3.0 +/- 1.6, 30 +/- 21, 39 +/- 26, 1.2 +/- 0.70, and
      0.62 +/- 0.65 ng/L, and their percent removals were 99 +/- 3.1, 78 +/- 8.8, 99 +/
      1.2, 98 +/- 2.5, 99 +/- 1.8, and 100 +/- 0%, respectively. The lower removal of
      prednisolone was found to be due to its relatively low efficiency of
      biodegradation, especially in anoxic and aerobic units. The frequently detected
      glucocorticoids in effluents were prednisolone, cortisol, and cortisone with
      average concentrations 0.56 +/- 0.06, 0.50 +/- 0.33, and 0.26 +/- 0.10 ng/ L. In
      the receiving waters, the Tonghui and Qing Rivers, the concentrations of these
      compounds in some samples were much higher than those in their corresponding STP
      effluents; these differences depended on the sampling date, suggesting that there
      was random discharging of untreated wastewaters into these rivers. In addition,
      the ratio between the combined concentrations of two natural glucocorticoids
      (cortisol and cortisone) and the concentration of one synthetic glucocorticoid,
      prednisolone, was found to be a potential index to reflect the wastewater
      discharging.

PMID- 17547165
TI  - A millennium of metallurgy recorded by lake sediments from Morococha, Peruvian
      Andes.
AB  - To date, information concerning pre-Colonial metallurgy in South America has
      largely been limited to the archaeological record of artifacts. Here, we
      reconstruct a millennium of smelting activity in the Peruvian Andes using the
      lake-sediment stratigraphy of atmospherically derived metals (Pb, Zn, Cu, Ag, Sb,
      Bi, and Ti) and lead isotopic ratios (206Pb/ 207Pb) associated with smelting from
      the Morococha mining region in the central Peruvian Andes. The earliest evidence
      for metallurgy occurs ca. 1000 A.D., coinciding with the fall of the Wari Empire
      and decentralization of local populations. Smelting during this interval appears
      to have been aimed at copper and copper alloys, because of large increases in Zn
      and Cu relative to Pb. A subsequent switch to silver metallurgy under Inca
      control (ca. 1450 to conquest, 1533 A.D.) is indicated by increases in Pb, Sb,
      and Bi, a conclusion supported by further increases of these metals during
      Colonial mining, which targeted silver extraction. Rapid development of the
      central Andes during the 20th century raised metal burdens by an order of
      magnitude above previous levels. Our results represent the first evidence for pre
      Colonial smelting in the central Peruvian Andes, and corroborate the sensitivity
      of lake sediments to pre-Colonial metallurgical activity suggested by earlier
      findings from Bolivia.

PMID- 17547166
TI  - Distinguishing respirable quartz in coal fly ash using computer-controlled
      scanning electron microscopy.
AB  - Determination and classification of quartz in coal fly ash (CFA) is a subject of
      interest because of the adverse health effects caused by inhalation of
      crystalline silica. Workers with prolonged exposure to this carcinogen can
      develop respiratory diseases over time. This obviously may include utility plant
      workers involved in the handling, loading, and hauling of CFA. In this
      investigation, computer-controlled scanning electron microscopy (CCSEM) and X-ray
      diffraction (XRD) were used to investigate Si-rich phases in CFA to develop a
      better approach for the determination of respirable quartz. Three CFA samples
      from utility boilers and a NIST standard CFA sample were investigated. The XRD
      measurements indicated that the four samples contained from 7.0 to 16.0 wt.% of
      quartz. The CCSEM measurements utilized both particle size distributions and a
      particle shape parameter, circularity, to classify the Si-rich phases in these
      ashes as either crystalline or amorphous (glass). The results indicated that the
      amount of free, respirable, quartz in these CFA samples ranged from only 0.1-1.0
      vol % and showed little correlation with the XRD results for the bulk ash. These
      results are significant in view of the factthat XRD is the traditional method of
      measuring crystalline silica in dust collected from workplace atmospheres.

PMID- 17547167
TI  - Urinary methoxyphenol biomarkers and woodsmoke exposure: comparisons in rural
      Guatemala with personal CO and kitchen CO, levoglucosan, and PM2.5.
AB  - Urinary methoxyphenols have been proposed as biomarkers for woodsmoke exposure,
      but few field studies have been undertaken. We evaluated these biomarkers for
      assessing the exposure to woodsmoke of householders in rural Guatemala. The study
      population was a subset (10 female cooks, 2 female non-cooks, and 8 male non
      cooks ranging in age from 7 to 60) drawn from those participating in a longterm
      randomized intervention trial (RESPIRE) in the highlands. All households rely
      solely on woodburning for cooking and home heating. Approximately half of the
      homes in the trial used open woodfires in the home, while the intervention group
      used cookstoves, called "planchas, "that vent most of the woodsmoke outdoors
      through a chimney. Corrected for creatinine levels, 16 of the 19 methoxyphenols
      measured were lower in the urine of cooks using the plancha; and 11 of the 19
      compounds were lower in the urine of non-cooks from homes using the plancha.
      Furthermore, the 4 low-molecular-weight syringyl methoxyphenols (syringol,
      methysyringol, ethylsyringol, propylsyringol) were each moderately correlated (r2
      = 0.71,0.64, 0.68, 0.53 respectively, with all p < 0.05) with personal exposure
      measurements determined by carbon monoxide (CO) passive diffusion tubes, but not
      with CO in exhaled breath. 48-Hour kitchen area measurements of PM2.5 mass, PM2.5
      levoglucosan, and CO were highly correlated (>0.89) with each other and
      moderately correlated (0.54-0.78) with personal CO measurements. Although based
      on relatively few measurements, this study demonstrates that the urinary
      concentrations of specific methoxyphenols may be effective biomarkers of short
      term exposures to inhaled woodsmoke in field conditions.

PMID- 17547168
TI  - Characterization and source apportionment of particulate matter < or = 2.5
      micrometer in Sumatra, Indonesia, during a recent peat fire episode.
AB  - An intensive field study was conducted in Sumatra, Indonesia, during a peat fire
      episode to investigate the physical and chemical characteristics of particulate
      emissions in peat smoke and to provide necessary data for source-receptor
      analyses. Ambient air sampling was carried out at three different sites located
      at varying distances from the peatfires to determine changes in mass and number
      concentrations of PM2.5 and its chemical composition (carbonaceous and
      nitrogenous materials, polycyclic aromatic hydrocarbons, water-soluble inorganic
      and organic ions, and total and water-soluble metals). The three sites represent
      a rural site directly affected by the local peat combustion, a semirural site,
      and an urban site situated downwind of the peat fires. The mass concentration of
      PM2.5 and the number concentration of airborne particles were as high as 1600
      microg/m3 and 1.7 x 10(5) cm(-3), respectively, in the vicinity of peat fires.
      The major components of PM2.5 in peat smoke haze were carbonaceous particles,
      particularly organic carbon, NO3-, and SO4(2-), while the less abundant
      constituents included ions such as NH4+, NO2-, Na+, K+, organic acids, and metals
      such as Al, Fe, and Ti. Source apportionment by chemical mass balance receptor
      modeling indicates that peat smoke can travel long distances and significantly
      affect the air quality at locations downwind.

PMID- 17547169
TI  - Enrichment of heavy metals in sediment resulting from soil erosion on
      agricultural fields.
AB  - Heavy metal pollution of soil and water is often associated with industry, but in
      this paper we demonstrate that water erosion on agricultural soil which has
      received only agrochemicals has enriched sediment metal concentrations to toxic
      levels which breach many accepted standards for soils and sediments. Eight 0.1 ha
      erosion plots with different cultivation treatments were monitored over a 6 year
      period for surface runoff, soil loss, and Cr, Cu, Pb, and Ni concentrations. Mean
      concentrations of these heavy metals were up to 3.98 times higher in the sediment
      than in the parent soil and in some erosion events the sediment had 13.5 times
      the concentration of metals in the soil. All the sediment heavy metal
      concentrations were significantly correlated (p < 0.01) with the clay and silt
      sized fractions of the sediment and with carbon content. The erosion was a highly
      selective process enriching the detached material in silt, clay, and organic
      carbon. This was particularly true in smaller erosion events. Sediment metal
      concentrations tended to follow the shape of runoff hydrographs, although the
      pattern changed from storm to storm.

PMID- 17547170
TI  - Spatial and habitat-based variations in total and methyl mercury concentrations
      in surficial sediments in the San Francisco Bay-Delta.
AB  - Recent studies indicate significant amounts of mercury (Hg) are annually
      transported into the San Francisco Bay-Delta (Bay-Delta) as a result of historic
      gold and Hg mining activities. We examined temporal and spatial variation in
      concentrations of total Hg (Hg(T)) and monomethylmercury (MMHg) in surficial
      sediments of various ecosystem types in the Bay-Delta. We sampled surficial
      sediments across the Bay-Delta system and found Hg(T) sediment concentrations in
      the central Delta were generally 100-200 ng g(-1) and increased westward through
      Suisun Bay to 250-350 ng g(-1). MMHg concentrations in the central Delta were
      between 1 and 3 ng g(-1), while those in sediments in the perimeter waterways and
      adjacent bays were less than 1 ng g(-1). Six sites were monitored monthly for
      over a year to identify seasonal changes in Hg sediment concentrations. Hgtau
      sediment concentrations ranged from 48 to 382 ng g(-1) and varied as a function
      of location not season. However, MMHg concentrations varied seasonally,
      increasing from 1 ng g(-1) during winter months to 6 ng g(-1) during spring and
      summer. Transects conducted at three marshes in the central Delta revealed MMHg
      sediment concentrations of 4-8 ng g(-1) at the interior and 2 ng g(-1) at the
      exterior of the marshes. Habitat type was a major factor controlling MMHg
      concentration and the MMHg to Hg(T) ratio in sediments of the Bay-Delta. MMHg was
      significantly correlated to Hgt (r2 = 0.49) in marsh sediments.

PMID- 17547171
TI  - Lead in bottled waters: contamination from glass and comparison with pristine
      groundwater.
AB  - Using clean lab methods and protocols developed for measuring lead (Pb) in polar
      snow and ice, we report the abundance of Pb in 125 brands of bottled water from
      28 countries. Comparison of six samples of each of three brands of water
      available in both glass and polyethyelene terephthalate (PET(E)) showed that the
      waters bottled in glass contained approximately 57, 30, and 26 times more Pb due
      to leaching from the containers. Excluding the bottled waters in glass, the
      median Pb concentration in all bottled waters was found to be 8.5 ng/L (n=185),
      with a range from <1 to 761 ng/L Pb. Our study includes 25 brands of bottled
      water from Canada, and the median Pb concentration in these samples was 15.9 ng/L
      (n=25), with a range from 2.1 to 268 ng/L. For comparison with the bottled
      waters, pristine groundwater from six artesian flows in southern Ontario, Canada,
      where some of the bottled waters originate, yielded a median concentration of 5.1
      ng/L Pb (n=18). The median Pb concentrations reported here for bottled waters
      from Canada are 32-588 times less than those presented in recently published
      studies. In fact, all of the waters tested were well below the maximum allowable
      concentration established by the EU, Health Canada, and the WHO for Pb in
      drinking water (10 microg/L).

PMID- 17547172
TI  - Rangeland grazing as a source of steroid hormones to surface waters.
AB  - Cattle and other livestock excrete endogenous steroid hormones, including
      estrogens, androgens, and progestins; therefore, allowing grazing livestock
      direct access to surface waters can result in the release of steroids in
      agricultural watersheds. Elevated concentrations of steroids are problematic
      because low concentrations of certain steroids can affect fish reproduction. To
      assess the occurrence and transport of steroids arising from grazing cattle, gas
      chromatography-tandem mass spectrometry (GC/MS/MS) was used to quantify a suite
      of estrogens, androgens, and progestins in small creeks impacted by rangeland
      grazing. Steroids were detected in 86% of samples from rangeland creeks where
      cattle had direct access to the water, with concentrations as high as 44 ng/L
      observed shortly after rain events at the beginning of the winter wet season.
      Estrogens were present at concentrations above the predicted no-effect
      concentrations for fish in 10-20% of the samples, and androstenedione was
      detected at concentrations higher than response thresholds for pheromonal
      communication in fish. The results suggest that, in certain cases, measures such
      as stream fencing in rangeland areas to limit direct discharge of animal wastes
      to surface waters or better manure management practices might be merited to
      protect ecosystem health.

PMID- 17547173
TI  - Prevalence of long-chained perfluorinated carboxylates in seabirds from the
      Canadian Arctic between 1975 and 2004.
AB  - Temporal trends in perfluoroalkyl compounds (PFCs) were investigated in liver
      samples from two seabird species, thick-billed murres (Uria lomvia) and northern
      fulmars (Fulmaris glacialis), from Prince Leopold Island in the Canadian Arctic.
      Thick-billed murre samples were from 1975, 1993, and 2004, whereas northern
      fulmars were from 1975, 1987, 1993, and 2003. Between 8 and 10 individuals were
      analyzed per year. Analytes included C7-C15 perfluorinated carboxylates (PFCAs)
      and their suspected precursors, the 8:2 & 10:2 fluorotelomer saturated and
      unsaturated carboxylates (FTCAs, FTUCAs), C6, C8 (perfluorooctane sulfonate,
      PFOS), C10 sulfonates, and perfluorooctane sulfonamide (PFOSA). Liver samples
      were homogenized, liquid-liquid extracted with methyl tert-butyl ether, cleaned
      up using hexafluoropropanol, and analyzed by LC-MS/ MS. Overall, concentrations
      in seabirds were lower than those in other marine animals that occupy similar or
      higher trophic positions. In contrast to most other wildlife samples, PFC
      profiles were dominated by the PFCAs which comprised 81% and 93% of total PFC
      profiles in the 2004 thick-billed murre and 2003 northern fulmar samples,
      respectively. As well, the PFCA profiles were mainly comprised of the C11-C15
      PFCAs, which appears to be unique among other wildlife species. PFC
      concentrations were found to increase significantly from 1975 to 2003/2004.
      Doubling times in thick-billed murres ranged from 2.3 yrs for
      perfluoropentadecanoate (PFPA) to 9.9 yrs for perfluorododecanoate (PFDoA), and
      from 2.5 yrs for PFPA to 11.7 yrs for perfluorodecanoate (PFDA) in northern
      fulmars. PFCA concentration increases in thick-billed murres were significant for
      both time periods (1975-1993, 1993-2004), but in northern fulmars appeared to
      remain steady after 1993. Differences in the temporal trends observed may be the
      result of differing migratory patterns of the seabirds. Finally, the detection of
      the 8:2 and 10:2 FTUCAs in seabirds is suggestive of fluorotelomer alcohols as a
      source of some PFCAs.

PMID- 17547174
TI  - Perfluoroalkyl contaminants in the Canadian Arctic: evidence of atmospheric
      transport and local contamination.
AB  - Perfluorosulfonates (PFSAs) and perfluorocarboxylates (PFCAs) have been
      hypothesized to reach remote locations such as the Canadian Arctic either
      indirectly as volatile precursor chemicals that undergo atmospheric transport and
      subsequent degradation, or directly via oceanic and atmospheric transport of the
      PFSAs and PFCAs themselves. Water, sediment, and air samples were collected from
      three Arctic lakes (Amituk, Char, and Resolute) on Cornwallis Island, Nunavut,
      Canada. Samples were analyzed for PFSAs and PFCAs, precursor chemicals including
      the fluorotelomer alcohols (FTOHs) and polyfluorinated sulfonamides (FSAs), and
      precursor degradation products such as the fluorotelomer unsaturated carboxylates
      (FTUCAs). PFSAs and PFCAs were detected in water and sediment of all three Arctic
      lakes (concentrations ranged from nondetect to 69 ng/L and nondetect to 85 ng/g
      dry weight, respectively). FTOHs and FSAs were observed in air samples (mean
      concentrations ranged from 2.8 to 29 pg/m3), and confirm that volatile precursors
      are reaching Arctic latitudes. The observation of degradation products, including
      FTUCAs observed in sediment and atmospheric particles, and N-ethyl
      perfluorooctanesulfonamide (NEtFOSA) and perfluorooctanesulfonamide (PFOSA) in
      air samples, indicate that degradation of the FTOHs and FSAs is occurring in the
      Arctic environment. PFSAs and PFCAs were also observed on atmospheric particles
      (mean concentrations ranged from < 0.1 to 5.9 pg/m3). In addition, results of
      this study also indicate that local perfluoroalkyl contamination of Resolute
      Lake, which is located downstream of an airport wastewater input, has occurred.

PMID- 17547175
TI  - Emission rates and characterization of aerosols produced during the spreading of
      dewatered class B biosolids.
AB  - This study measured aerosol emission rates produced during the spreading of
      dewatered class B biosolids onto agricultural land. Rates were determined in
      multiple independent experimental runs by characterizing both the source aerosol
      plume geometry and aerosol concentrations of PM10, total bacteria, heterotrophic
      plate count bacteria (HPC), two types of biosolids indicator bacteria, endotoxin,
      and airborne biosolids regulated metals. These components were also measured in
      the bulk biosolids to allow for correlating bulk biosolids concentrations with
      aerosol emission rates and to produce reconstructed aerosol concentrations. The
      average emission rates and associated standard deviation for biosolids PM10,
      total bacteria, HPC, total coliforms, sulfite-reducing Clostridia, endotoxin, and
      total biosolids regulated metals were 10.1 +/- 8.0 (mg/s), 1.98 +/- 1.41 x 10(9)
      (no./s), 9.0 +/- 11.2 x 10(7) (CFU/s), 4.9 +/- 2.2 x 10(3) (CFU/ s), 6.8 +/- 3.8
      x 10(3) (CFU/s), 2.1 +/- 1.8 x 10(4) (EU/s), and 36.9 +/- 31.8 (microg/s)
      respectively. Based on the land application rates of spreaders used in this
      study, an estimated 7.6 +/- 6.3 mg of biosolids were aerosolized for every 1 kg
      (dry weight) applied to land. Scanning electron microscopy particle size
      distribution analysis of the aerosols revealed that greater than 99% of the
      emitted particles were less than 10 microm and particle size distributions had
      geometric mean diameters and standard deviations near 1.1 +/- 0.97 microm. The
      demonstrated correlations of bulk biosolids concentrations with aerosol emission
      rates, and the reconstruction of aerosol concentration based on PM10 and bulk
      biosolids concentration provide a more fundamental, bulk biosolids-based approach
      for extending biosolids aerosol exposure assessment to different land application
      scenarios and a broader range of toxins and pathogens.

PMID- 17547176
TI  - Reactions of semivolatile organics and their effects on secondary organic aerosol
      formation.
AB  - Secondary organic aerosol (SOA) constitutes a significant fraction of total
      atmospheric particulate loading, but there is evidence that SOA yields based on
      laboratory studies may underestimate atmospheric SOA. Here we present chamber
      data on SOA growth from the photooxidation of aromatic hydrocarbons, finding that
      SOA yields are systematically lower when inorganic seed particles are not
      initially present. This indicates that concentrations of semivolatile oxidation
      products are influenced by processes beyond gas-particle partitioning, such as
      chemical reactions and/or loss to chamber walls. Predictions of a kinetic model
      in which semivolatile compounds may undergo reactions in both the gas and
      particle phases in addition to partitioning are qualitatively consistent with the
      observed seed effect, as well as with a number of other recently observed
      features of SOA formation chemistry. The behavior arises from a kinetic
      competition between uptake to the particle phase and reactive loss of the
      semivolatile product. It is shown that when hydrocarbons react in the absence of
      preexisting organic aerosol, such loss processes may lead to measured SOA yields
      lower than would occur under atmospheric conditions. These results underscore the
      need to conduct studies of SOA formation in the presence of atmospherically
      relevant aerosol loadings.

PMID- 17547177
TI  - Atmospheric outflow of anthropogenic semivolatile organic compounds from East
      Asia in spring 2004.
AB  - To estimate the emissions of anthropogenic semivolatile organic compounds (SOCs)
      from East Asia and to identify unique SOC molecular markers in Asian air masses,
      high-volume air samples were collected on the island of Okinawa, Japan between 22
      March and 2 May 2004. Contributions from different source regions (China, Japan,
      the Koreas, Russia, and ocean/local) were estimated by use of source region
      impact factors (SRIFs). Elevated concentrations of hexachlorobenzene (HCB),
      hexachlorcyclohexanes (HCHs), dichlorodiphenyltrichloroethanes (DDTs), and
      particulate-phase polycyclic aromatic hydrocarbons (PAHs) were attributed to air
      masses from China. A large proportion of the variation in the current-use
      pesticides, gas-phase PAHs, and polychlorinated biphenyl (PCB) concentrations was
      explained by meteorology. Chlordanes showed a technical mixture profile and
      similar concentrations regardless of source region. alpha/gamma HCH and trans/cis
      chlordane ratios did not vary significantly with different source regions and had
      regional averages of 2.5 +/- 1.0 and 1.2 +/- 0.3, respectively. Particulate-phase
      PAH concentrations were significantly correlated (p value < 0.05) with other
      incomplete combustion byproduct concentrations, including elemental mercury
      (Hg0), CO, NOx, black carbon, submicrometer aerosols, and SO2. By use of measured
      PAH, CO, and black carbon concentrations and estimated CO and black carbon
      emission inventories, the emission of six carcinogenic particulate-phase PAHs was
      estimated to be 1518-4179 metric tons/year for Asia and 778-1728 metric tons/year
      for China, respectively. These results confirm that East Asian outflow contains
      significant emissions of carcinogenic particulate-phase PAHs.

PMID- 17547178
TI  - Importance of structural makeup of biopolymers for organic contaminant sorption.
AB  - Sorption of pyrene, phenanthrene, naphthalene, and 1-naphthol by original
      (lignin, chitin, and cellulose) and coated biopolymers was examined. Organic
      carbon normalized distribution coefficients (Koc) of all compounds by the
      original biopolymers followed the order lignin > chitin > cellulose, in line with
      the order of their hydrophobicity. Hydrophobicity of structurally similar organic
      compounds is the main factor determining their ability to occupy sorption sites
      in biopolymers. Specific interactions (e.g., H-bonding) between 1-naphthol and
      chitin or cellulose increased its ability to occupy sorption sites. Lignin
      coating resulted in an increased Koc for phenanthrene (13.6 times for chitin and
      6.9 times for cellulose) and 1-naphthol (6.0 times for chitin and 3.7 times for
      cellulose) relative to the acetone-treated chitin and cellulose. Also, these
      coated biopolymers had increased isotherm nonlinearity, due to the newly formed
      condensed domains. An increase in phenanthrene and 1-naphthol sorption by lignin
      coated biopolymers as compared to chitin and cellulose was contributed by the
      newly created high-energy sites in condensed domains and coated lignin. Results
      of this study highlight the importance of the structural makeup of biopolymers in
      controlling the sorption of hydrophobic organic compounds.

PMID- 17547179
TI  - Deposition of glomalin-related soil protein and sequestered toxic metals into
      watersheds.
AB  - We hypothesized that glomalin-related soil proteins (GRSP) are eroded in
      sufficient quantities to influence metal loading into watersheds. We tested
      correlations among GRSP, Glomeromycota fungi, and metals (cadmium, iron, lead,
      and manganese) in proteins extracted from embankment soils at seven locations
      along an urban/coastal watershed. Immunoreactive (IRSP) and easily extractable
      (EE-IRSP) glomalin ranged from 0.007 to 2.9 mg g(-1) and from 0.006 to 0.63 mg g(
      1) of soils, respectively. Glomalin-bound metals (microg mg(-1) protein) were Cd
      = 0.00-0.338; Fe = 0.5-227.7; Pb = 0.11-188.95; Mn = 2.23-784.42). Glomeromycota
      fungi were detected in 24% of all samples tested with PCR targeting the 18S and
      28S ribosomal DNA extracted from soils. Specific assay for G. intraradices showed
      3.08 x 10(7) copies g(-1) and 1.96 x 10(3) copies g(-1) of soil at two sites.
      Estimated annual glomalin loading into the watershed ranged from 5.48 x 10(2) to
      7.22 x 10(4) kg of IRSP and from 2.57 x 102 to 2.86 x 10(4) kg of EE-IRSP;
      including 2.7 kg (Cd), 6.3 x 10(3) kg (Fe), 5.06 x 10(2) kg (Pb), and 1.80 x
      10(3) kg (Mn). These data provide insights into the sources and ecological fate
      of a ubiquitous soil protein and its metals content.

PMID- 17547180
TI  - Anaerobic degradation of linear alkylbenzene sulfonates in coastal marine
      sediments.
AB  - This research shows for the first time the degradation of linear alkylbenzene
      sulfonates (LAS) under anaerobic conditions, together with the presence of
      metabolites and the identification of microorganisms involved in this process.
      This compound is the most widely used surfactant and its main environmental
      concern is related to its persistence in the absence of oxygen as LAS accumulates
      in anaerobic sediments and sewage sludges. Laboratory experiments performed with
      anoxic marine sediments spiked with 10-50 ppm of LAS demonstrated, however, that
      its degradation reached 79% in 165 days via the generation of sulfophenyl
      carboxylic acids (SPCs). Almost all of the added LAS (>99%) was found to be
      attached to the sediment while the less hydrophobic SPCs were predominant in
      solution, as their concentration increased progressively up to 3 ppm during the
      full course of the experiment. Average half-life for LAS has been estimated to be
      90 days, although higher values should be expected when the LAS concentration
      exceeds 20 ppm, due to inhibition of the microbial community. Sulfate-reducing
      and methanogenic activities proved to be intense during the experiment. Several
      sulfate-reducing bacteria and firmicutes/clostridia have been identified as
      possible candidates for effecting this degradation. Our results imply that the
      persistence of LAS in anoxic compartments, such as marine sediments, should be
      reconsidered when evaluating its environmental risk.

PMID- 17547181
TI  - Monitoring the primary biodegradation of linear alkylbenzene sulfonates and their
      coproducts in anoxic sediments using liquid chromatography-mass spectrometry.
AB  - An accompanying article has demonstrated the anaerobic degradation of the
      surfactant linear alkylbenzene sulfonate (LAS) in microcosms filled with marine
      sediments through the generation of sulfophenylcarboxylic acids (SPCs). A
      detailed study shows that this process was uniform in the blanks (non-spiked
      natural sediments) for every LAS homologue during the complete course of the
      experiment. However, when sediments were spiked with commercial LAS and,
      therefore, enriched with short-chain homologues, degradation was enhanced for
      these homologues until their percentages were close to those for non-spiked
      sediments. The reason is that short-chain homologues are more bioavailable due to
      their higher solubility and lower sorption capacity. Thus, sorption on sediments
      was found to be increased with the length of the alkyl chain for LAS homologues,
      following a linear Freundlich isotherm, whereas the metabolites generated were
      predominant in solution due to their much higher polarity. Intermediate-chain SPC
      homologues (C7-C9 SPCs) were the most abundant during the experiment, but a
      significant increase in the concentration of shorter-chain SPC homologues (C4-C6
      SPCs) was detected toward the end. In the case of isomers, the steric effect of
      the aromatic group implies that LAS primary degradation took place preferentially
      over external isomers. Therefore, the generation of external isomers of SPCs was
      predominant during the complete experiment although internal isomers of SPCs
      became more evident when the degradation process had advanced and external
      isomers of LAS became scarce. The identity of both types of SPC isomer was
      confirmed by tandem mass spectrometry. With respect to LAS coproducts, the
      relative percentage of iso-LAS increased during the complete experiment and
      removal percentages for dialkyl tetralinsulfonates (<30%) were typically lower
      that those for LAS (66-79%), although a similar behavior was observed for their
      homologues in both cases.

PMID- 17547182
TI  - Surface complexation modeling of U(VI) sorption to Hanford sediment with varying
      geochemical conditions.
AB  - A series of U(VI) sorption experiments with varying pH, ionic strength,
      concentrations of dissolved U(VI), and alkalinity was conducted to provide a more
      realistic database for U(VI) sorption onto near-field vadose zone sediments at
      the proposed Integrated Disposal Facility (IDF) on the Hanford Site, Washington.
      The distribution coefficient (Kd) for U(VI) in a leachate that is predicted to
      result from the weathering of vitrified wastes disposed in the IDF is 0 mL/g due
      to the high sodium and carbonate concentrations and high pH of the glass
      leachate. However, when the pH and alkalinity of the IDF sediment native pore
      water increases during mixing with the glass leachate, U(VI) uptake is observed
      and the value of the U(VI) Kd increases 4.3 mL/g, because of U(VI)
      coprecipitation with newly formed calcite. A nonelectrostatic, generalized
      composite approach for surface complexation modeling was applied and a
      combination of two U(VI) surface species, monodentate (SOUO2+), and bidentate
      (SO2UO2(CO3)2-), simulated the measured U(VI) sorption data very well. The
      generalized composite surface complexation model, when compared to the constant
      or single-valued Kd model, more accurately predicted U(VI) sorption under the
      varying geochemical conditions expected at the IDF.

PMID- 17547183
TI  - Laccase-mediated michael addition of 15N-sulfapyridine to a model humic
      constituent.
AB  - Chemical incorporation of sulfonamide antimicrobials into natural organic matter
      may represent an important process influencing the fate of these synthetic,
      primarily agents in soil and sediment environments. We previously demonstrated
      that a fungal peroxidase mediates covalent coupling of sulfonamide antimicrobials
      to model humic constituents; reactions with the 2,6-dimethoxyphenol syringic acid
      produced Schiff bases (Bialk et al. Environ. Sci. TechnoL 2005, 39, 4436-4473).
      Here, we show that fungal laccase-mediated reaction of sulfapyridine with the
      orthodihydroxyphenol protocatechuic acid yields a Michael adduct. We synthesized
      15N-enriched sulfapyridine to facilitate determination of the covalent linkage(s)
      formed between sulfapyridine and protocatechuic acid by NMR spectroscopy. 1H
      (15)N heteronuclear multiple bond correlation experiments and tandem mass
      spectrometry demonstrated that the sulfapyridine anilinic nitrogen engaged in a
      Michael addition reaction to oxidized protocatechuic acid to form an
      anilinoquinone. Michael adducts are more stable than the previously reported
      imine linkages between sulfonamides and 2,6-dimethoxyphenols. Michael addition to
      quinone-like structures in soil organic matter is expected to diminish the
      mobility and biological activity of sulfonamide antimicrobials.

PMID- 17547184
TI  - Selenomethionine biotransformation and incorporation into proteins along a
      simulated terrestrial food chain.
AB  - Selenium is an essential trace element in vertebrates, but there is a narrow
      concentration range between dietary requirement and toxicity threshold. Although
      a great deal is known about the biochemistry of Se from a nutritional
      perspective, considerably less attention has been focused on the specific
      biochemistry of Se as an environmental toxicant. Recent advances in hyphenated
      analytical techniques have provided the capability of quantifying specific
      chemical forms of Se in biological tissues as well as the distribution of Se
      among macromolecules. We applied liquid chromatography coupled to inductively
      coupled plasma mass spectrometryto investigate biotransformations of
      selenomethionine along a simulated terrestrial food chain consisting of
      selenomethionine exposed crickets (Acheta domesticus) fed to western fence
      lizards (Sceloporus occidentalis). Evidence was obtained for selenomethionine
      biotransformation as well as for sex-specific differences in the metabolism of Se
      compounds and their subsequent incorporation into proteins in the lizard. The
      results demonstrate the complexities involved in trophic transfer of Se due to
      the potential for extensive biotransformation and the species- and even sex
      specific nature of these biotransformations.

PMID- 17547185
TI  - Natural production of organic bromine compounds in Berlin Lakes.
AB  - Berlin surface waters are characterized by elevated concentrations of organic
      bound bromine (up to 35 microg/L) in late summer. Organic bromine compounds in
      lakes are of significant importance because human life is closely connected to
      fresh water. Apart from recreational use, fresh water is frequently used for the
      production of drinking water, e.g., after bank filtration. Therefore the source,
      particularly the mechanism responsible for the formation is studied. Field
      studies indicate that the organic bromine compounds, measured as adsorbable
      organic bromine (AOBr), are autochthonous. Staggered maxima concentrations of
      chlorophyll-a, DOC and AOBr indicate that phototrophic organisms might contribute
      to the AOBr after death. The involvement of phototrophic organisms was
      established in the laboratory using surface water and/or cultures of organisms.
      Light and the presence of phototrophic organisms are essential for an AOBr
      production. Phototrophic organisms incorporate bromide, which is released
      randomly and after cell death. A part of the incorporated bromide is used for the
      formation of organic bromine compounds in the cell. After death of the organisms
      the brominated compounds and the incorporated bromide are released into the water
      phase, and an extracellular AOBr production can lead to a further formation of
      AOBr, most probably due to the parallel release of haloperoxidases.

PMID- 17547186
TI  - Relationship between the adsorption capacity of pesticides by wood residues and
      the properties of woods and pesticides.
AB  - With the aim to explore the potential use of wood residues in technologies aimed
      at preventing the pollution of soil and water, we studied the adsorption of four
      non-ionic pesticides (linuron, alachlor, metalaxyl, and chlorpyrifos) and two
      ionic pesticides (dicamba and paraquat) with a Kow range of -4.5 to 4.7 by nine
      types of wood with lignin content in the 18.2-26.9% range. The Freundlich Kf
      values were considered as indicators of the adsorption capacity. A statistical
      study was carried out using simple and multiple correlations to establish the
      degree to which the different parameters of the woods and of the pesticides were
      involved in adsorption. In the case of the non-ionic pesticides, positive and
      negative significant correlations were observed between Kf and the lignin (r =
      0.73-0.83, p < 0.05-0.01), and soluble C contents of the woods (r = 0.66-0.84), p
      < 0.1-0.01). For dicamba, a correlation between Kf and pH (r = -0.66, p < 0.1) of
      the woods was found, while for paraquat, this was seen between Kf and the cation
      exchange capacity (r = 0.71, p < 0.1) of the woods. No significant correlation
      was observed between Kf and the total C content of the woods. A highly
      significant correlation between Kf and Kow values (r > or = 0.93, p < 0.01) was
      found in the adsorption of the pesticides by the woods (with the exception of
      paraquat) showing that this parameter is very important in this adsorption
      process. The determination coefficient of the multiple correlation between Kf and
      the parameters Kow, soluble C, and lignin contents accounts for nearly 100% of
      the variability in adsorption for non-ionic pesticides. Based on the results of
      our study and of those of the literature related to the adsorption of aromatic
      hydrocarbons, we used the Kow values to define a predictive model of adsorption
      of hydrophobic organic compounds in general by the woods.

PMID- 17547187
TI  - Phylogenetic analysis implicates birds as a source of Cryptosporidium spp.
      oocysts in agricultural watersheds.
AB  - Cryptosporidium parvum and C. hominis are protozoan parasites responsible for
      cryptosporidiosis, an acute gastrointestinal illness that can be life-threatening
      for immunocompromised persons. Sources and genotypes of Cryptosporidium oocysts
      were investigated in two agricultural areas within the Wachusett Reservoir
      watershed, a drinking water source for Boston, Massachusetts. Two brooks (denoted
      Brook SF and Brook JF, respectively), each downgradient from a dairy farm, were
      chosen as sample sites. For one year, Brooks SF and JF were sampled monthly;
      oocysts were detected in 6 (50%) out of 12 samples from Brook JF, and no oocysts
      were detected in Brook SF. Oocyst genotypes from agricultural surface waters were
      compared to oocyst genotypes from Genbank, as well as fecal samples of cattle and
      birds, using phylogenetic analysis of a hypervariable region of the 18S rRNA gene
      by both neighbor-joining and parsimony methods. Results show extensive
      heterogeneity among Cryptosporidium spp. 18S rRNA sequences, and also suggest
      that birds are an oocyst source in this watershed. Principal components analysis
      showed oocyst presence correlating strongly with seasonal factors, and oocysts in
      surface waters were only detected in the summer through late fall, co-incident
      with the presence of migratory birds in this watershed. If birds are confirmed to
      be an important source of oocysts infectious to humans, the data suggest that
      protection of raw drinking water supplies in some agricultural areas may depend
      upon management and control of resident and migratory bird populations.

PMID- 17547188
TI  - Temperature and wavelength dependence of nitrite photolysis in frozen and aqueous
      solutions.
AB  - While the photolysis of nitrite is an important source of hydroxyl radical (*OH)
      in some natural waters, its wavelength and temperature dependence have not been
      fully described in solution. In addition, there are no studies of this reaction
      on ice, although there is evidence of nitrite production in snow. To address
      these gaps, we have measured the wavelength and temperature dependence of the
      quantum yields of *OH from the photolysis of frozen and aqueous NO2-. From our
      solution and ice results, we derive a master equation that describes the *OH
      quantum yield from NO2 photolysis as a function of both temperature (240-295 K)
      and illumination wavelength (302-390 nm): phi(NO1- -->OH*)(T,lamda) = (Y0 + a/(1
      + exp((lamda-c)/b)))exp-(((e lamda) + f)/R) x (1/295 - 1/T)) where Y0 = 0.0204 +/
      0.0010, a = 0.0506 +/- 0.0022, b = 11.2 +/- 1.2, c = 332 +/- 1, e = 20.5 +/-
      3.2, f = 7553 +/- 1204, uncertainties represent 1 standard error, Tis the
      temperature (K), Ris the gas constant (8.314 J mol(-1) K(-1)), and lamda is the
      wavelength (nm). Using these results we predict the pseudo-steady-state
      concentrations of nitrite on sunlit polar snow grains and compare the relative
      importance of the photolysis of nitrite, nitrate, and hydrogen peroxide as
      sources of snow-grain *0H.

PMID- 17547189
TI  - Low concentrations of surfactants enhance siderophore-promoted dissolution of
      goethite.
AB  - Surface-active agents (surfactants) are released by many soil bacteria and plant
      roots and are also important as environmental contaminants. Their presence at
      interfaces could influence important biogeochemical processes in soils such as
      ligand-controlled dissolution, an important process in biological iron
      acquisition. To investigate their potential influence on ligand-controlled
      dissolution of iron oxides, we studied the dissolution kinetics of goethite
      (alpha FeOOH) at pH 6 in the presence of the bacterial siderophore
      desferrioxamine B (DFOB) and the anionic surfactant sodium dodecyl sulfate (SDS).
      The adsorption isotherm of SDS on goethite showed an increase in the slope at
      concentrations ranging between 300 and 400 microM SDS in solution. This increase
      in slope suggested the onset of admicelle formation. Adsorption of DFOB onto
      goethite increased strongly with increasing concentrations of adsorbed SDS. Small
      concentrations of SDS (5 microM) resulted in a 3-fold acceleration of DFOB
      controlled goethite dissolution in the presence of 80 microM DFOB, compared to
      the suspensions without SDS. The effects of SDS on the goethite dissolution rates
      were less pronounced at higher SDS concentrations, and became negligible above
      600 microM total SDS. The dissolution rates of goethite were not proportional to
      the adsorbed DFOB concentrations, as would be expected for ligand-controlled
      dissolution. We speculate that increasing concentrations of adsorbed SDS result
      in a change in DFOB surface speciation from inner-sphere to outer-sphere
      complexes and, consequently, the ligand-controlled dissolution rates are not
      linearly related to the adsorbed DFOB concentration. Our results provide the
      first evidence for an important role of biosurfactants in biological iron
      acquisition involving siderophores.

PMID- 17547190
TI  - Mobilization of arsenic during one-year incubations of grey aquifer sands from
      Araihazar, Bangladesh.
AB  - Elevated As concentrations in shallow groundwater pose a major health threat in
      Bangladesh and similarly affected countries, yet there is little consensus on the
      mechanism of As release to groundwater or how it might be influenced by human
      activities. In this study, the rate of As release was measured directly with
      incubations lasting 11 months, using sediment and groundwater collected
      simultaneously in Bangladesh and maintained under anaerobic conditions throughout
      the study. Groundwater and gray sediment were collected as diluted slurries
      between 5 and 38 m in depth, a range over which ambient groundwater As
      concentrations increased from 20 to 100 microg L(-1). Arsenic was released to
      groundwater in slurries from 5 and 12 m in depth at a relatively constant rate of
      21 +/- 4 (2 sigma) and 23 +/- 6 microg As kg(-1) yr(-1), respectively. Amendment
      with a modest level of acetate increased the rate of As release only at 12 m (82
      +/- 18 mirog kg(-1) yr(-1)). Although the groundwater As concentration was
      initially highest at 38 m depth, no release of As was observed. These results
      indicate that the spatial distribution of dissolved As in Bangladesh and local
      rates of release to groundwater are not necessarily linked. Iron release during
      the incubations did not occur concurrently with As release, providing further
      confirmation thatthe two processes are not directly coupled. Small periodic
      additions of oxygen suppressed the release of As from sediments at all three
      depths, which supports the notion that anoxia is a prerequisite for accumulation
      of As in Bangladesh groundwater.

PMID- 17547191
TI  - Quantum chemical modeling of humic acid/air equilibrium partitioning of organic
      vapors.
AB  - Classical approaches for predicting soil organic matter partition coefficients of
      organic compounds require a calibration with experimental partition data and, for
      good accuracy, experimental compound descriptors. In this study we evaluate the
      quantum chemical model COSMO-RS in its COSMOtherm implementation for the
      prediction of about 200 experimental Leonardite humic acid/air partition
      coefficients without calibration or experimental compound descriptors, but simply
      based on molecular structures. For this purpose a Leonardite Humic Acid model
      monomer limited to 31 carbon atoms was derived from 13C NMR analysis, elemental
      analysis, and acidic function analysis provided in the literature. Altogether the
      COSMOtherm calculations showed a good performance and we conclude that it may
      become a very promising tool for the prediction of sorption in soil organic
      matter for compounds for which the molecular structure is the only reliable
      information available. COSMOtherm can be expected to be very robust with
      respectto new and complex compound structures because its calculations are based
      on a fundamental assessment of the underlying intermolecular forces. In contrast,
      other empirical models that are also based on the molecular structure of the
      sorbate have an application domain that is limited by their calibration data set
      that is often unknown to the user.

PMID- 17547192
TI  - Uncertainty-accounting environmental policy and management of water systems.
AB  - Environmental policies for water quality and ecosystem management do not commonly
      require explicit stochastic accounts of uncertainty and risk associated with the
      quantification and prediction of waterborne pollutant loads and abatement
      effects. In this study, we formulate and investigate a possible environmental
      policy that does require an explicit stochastic uncertainty account. We compare
      both the environmental and economic resource allocation performance of such an
      uncertainty-accounting environmental policy with that of deterministic, risk
      prone and risk-averse environmental policies under a range of different
      hypothetical, yet still possible, scenarios. The comparison indicates that a
      stochastic uncertainty-accounting policy may perform better than deterministic
      policies over a range of different scenarios. Even in the absence of reliable
      site-specific data, reported literature values appear to be useful for such a
      stochastic account of uncertainty.

PMID- 17547193
TI  - Modeling the transport of metals with rate-limited EDTA-promoted extraction and
      dissolution during EDTA-flushing of copper-contaminated soils.
AB  - EDTA-flushing of artificially contaminated soils enhanced Cu extraction but also
      induced mineral dissolution simultaneously. The mobilization and transport of
      these metal-EDTA complexes was investigated with column experiments. A
      quantitative transport model was proposed for simulating the experimental
      breakthrough curves of Cu, Fe, Al, and Ca. The rate-limited EDTA-promoted
      extraction and dissolution could be described by respective second-order kinetic
      terms, which were necessary for explaining the time-dependent depletion of
      extractable metals (sorbed and indigenous) in soils with continuous EDTA
      flushing. Simultaneous simulation of extraction of sorbed Cu and dissolution of
      soil Fe, Al, and Ca is more conceptually accurate than individual modeling of
      each metal because the latter approach tends to overestimate the concentration of
      free EDTA during transport and thus underestimate the rate coefficients of EDTA
      promoted dissolution. The fitted rate coefficients of Cu were about an order of
      magnitude larger than those of Fe and Al; these values probably reflect Cu
      extraction from weakly sorbed fractions and Fe and Al dissolution from amorphous
      oxides. The apparent retardation of Fe, Al, and Ca transport had to be taken into
      account by empirical determination, which was attributed to the metal lability in
      soils and thermodynamics of surface complexation.

PMID- 17547194
TI  - Evaluating aquatic toxicity by visual inspection of thallus color in the green
      macroalga Ulva: testing a novel bioassay.
AB  - A novel bioassaythat uses visual inspection of reproduction of the aquatic green
      macroalga Ulva has been developed for testing toxic chemicals. The method employs
      a technique to quantify percentage reproduction based on thallus color change
      during the progression of reproduction. The validity of visual inspection as a
      reliable method was supported by a high test score (80.4) from a test of the
      ability of 97 first year university students with no biology background to
      evaluate reproduction by visual observation after 30 min training. The
      sensitivity of the method was assessed using a reference toxicant (sodium dodecyl
      sulfate; SDS; EC50 = 7.1 mg x L(-1)), heavy metals Cu (0.063 mg x L(-1)), Cd
      (0.217 mg x L(-1, Pb (0.840 mg x L(-1)), Zn (0.966 mg x L(-1)), formalin (1.458
      mg x L(-1)), diesel fuel (3.7 mL x L(-1)), and is shown to be similar or better
      than more established aquatic toxicity bioassays. Toxicity data obtained by the
      Ulva bioassay for elutriates of sludge collected from nine different locations
      were directly compared with the commercially available Microtox test. Ulva
      reproduction was significantly inhibited in all elutriates with the greatest and
      least toxic effects, estimated by toxicity units (TU) observed in elutriates from
      industrial waste (13.1 TU) and a filtration bed (4.8 TU), whereas values ranging
      from 1 to 4.5 TU were obtained from the Microtox test, confirming that the Ulva
      bioassay is more sensitive. Correlation analyses for EC50 data versus the
      concentrations of toxicants in the sludge indicated a significant relationship
      between toxicity and four heavy meals (Cd, Cu, Pb, Zn) for the Ulva bioassay but
      no such correlation was detected by the Microtox test. The new bioassay method is
      simple to use, easy to interpret, economical, and eco-relevant so would be a
      valuable addition to aquatic toxicity testing protocols for a wide range of
      toxicants. Moreover, since Ulva has a wide geographical distribution and species
      have similar reproductive processes, the test method has worldwide application.

PMID- 17547195
TI  - Characterization of NAPL source zone architecture and dissolution kinetics in
      heterogeneous porous media using magnetic resonance imaging.
AB  - A direct visualization method using magnetic resonance imaging (MRI) was
      developed to characterize sand grain size distribution, nonaqueous phase liquid
      (NAPL) source zone architecture, and aqueous flowpaths in a three-dimensional (3
      D) flowcell (26.5 cm x 10.5 cm x 10.5 cm) packed with a heterogeneous
      distribution of five different sand fractions. All images were acquired at a
      resolution of 0.1875 cm x 0.1875 cm x 0.225 cm. A 1H image of pore water resolved
      the heterogeneous permeability field; grain size differences as small as 0.1 mm
      could be distinguished. A time series of 1H images of water doped with the
      paramagnetic tracer MnCl2 were acquired and used to obtain voxel-scale
      breakthrough curves. Water preferentially flowed through coarse sands before NAPL
      release. After NAPL release, the flow bypassed NAPLzones, and bypassing was more
      evident for high NAPL saturation zones. A time series of 19F images of NAPL were
      acquired and used to determine voxel-scale NAPL saturation (Sn) during
      dissolution. Results show that 93% of NAPL mass was in the coarsest sand, most
      NAPL was trapped as pools and not as residual ganglia, NAPL saturation increased
      with depth, and the NAPL dissolution front moved vertically from the top to the
      bottom of the flowcell during the first 170 pore volumes of waterflushed. NAPL
      component effluent concentrations initially increased due to the development of
      flow in zones with decreasing NAPL saturation. Flowpath images suggest that this
      occurs as NAPL transitions from pools (Sn > 0.15) to residual ganglia. The
      results highlight the importance of flow bypassing and provide the opportunity to
      develop more accurate NAPL dissolution models.

PMID- 17547196
TI  - Determining residence patterns of rainbow trout using laser ablation inductively
      coupled plasma mass spectrometry (LA-ICP-MS) analysis of selenium in otoliths.
AB  - Toxicological studies are often hampered by concerns of fish residency in the
      industrial effluent being evaluated. Contaminants in muscle or visceral tissue
      are useful indicators of recent exposure, but depuration, metabolic
      transformation, and tissue recompartmentalization of contaminants makes their use
      as temporal markers tenuous. Otoliths are metabolically stable and can provide
      temporal resolution for exposure to some elements that are incorporated into
      their calcified structure, including the divalent cations Sr, Zn, and Mn. Here we
      provide the first determinations of selenium, an anion in biological systems, in
      the otoliths of rainbow trout captured from a site receiving runoff with elevated
      selenium from a coal mine operation. Concentrations of selenium in annual growth
      zones of otoliths suggest that fish from the mine-impacted system are recent
      immigrants from nearby reference streams not receiving selenium-bearing effluent.

PMID- 17547197
TI  - On-line monitoring system of P5CDF homologues in waste incineration plants using
      VUV-SPI-IT-TOFMS.
AB  - It usuallytakes a few weeks to analyze dioxin concentrations and dioxin-TEQ
      (toxicity equivalency quantity) in fluegases from municipal solid waste (MSW)
      incinerators by a standard method provided by Japanese industrial standard (JIS
      0311). To reduce the required time for analysis, we have developed a new on-line
      measuring system for furans homologues. This system is composed of a sensitive
      and robust vacuum ultraviolet (VUV) single-photon ionization (SPI) ion trap (IT)
      time-of-flight mass spectrometer (VUV-SPI-IT-TOFMS) and automatic
      sampling/concentrating process. In this work, pentachloro-dibenzofuran (P5CDF)
      was selected as an index homologue in chlorinated dibenzo-p-dioxin/ furan
      homologues (DXNs) because its concentration and I-TEF (international toxicity
      equivalency factor), which are 2,3,4,7,8-P5CDF is 0.5 and 1,2,3,7,8-P5CDF is
      0.05, are high and the concentration correlates closely with the total amount of
      dioxin-TEQ. The lowest detectable limit, 1 pg (0.001 ng-TEQ/m3 N) was
      demonstrated by laboratory tests. This system underwent a field test at several
      actual MSW plants and the tests revealed the following: (a) This system is
      applicable for dioxin-TEQ evaluation from actual MSW incinerators. (b) It can
      continuously monitor P5CDF in a fluegas for 7 months. (c) The frequency of the
      measurements is once every 2-6 h, depending on the concentration of P5-CDF.

PMID- 17547198
TI  - Applicability of stable isotope fractionation analysis for the characterization
      of benzene biodegradation in a BTEX-contaminated aquifer.
AB  - In recent years the analysis of stable isotope fractionation has increasingly
      been used for characterizing and quantifying biodegradation of contaminants in
      aquifers. The correlation of carbon and hydrogen isotope signatures of benzene in
      a BTEX-contaminated aquifer located in the area of a former hydrogenation plant
      gave indications that biodegradation mainly occurred under anoxic conditions.
      This finding was consistent with the investigation of hydrogeochemical conditions
      within the aquifer. Furthermore, the biodegradation of benzene was calculated by
      changes in carbon isotope signatures using the Rayleigh-equation-streamline
      approach. Since contaminant concentrations can be also affected by nonisotope
      fractionating abiotic processes such as dilution, volatilization, or irreversible
      sorption to the aquifer matrix, the Rayleigh-equation-streamline approach was
      adjusted for scenarios assuming that biodegradation and abiotic processes occur
      either consecutively or simultaneously along a groundwater flow path between
      contaminant source and sampling well. The results of the scenarios differed
      significantly, indicating that an abiotic process (typically dilution) causes a
      decrease in benzene concentration within the investigated aquifer transect. This
      comparison of results derived from the different scenarios can help to identify
      whether biodegradation is the predominant process for decrease in contaminant
      concentration. However, for a proper quantification of biodegradation, the
      temporal sequence between biodegradation and dilution needs to be known. The
      uncertainty associated with the quantification of pollutant biodegradation by the
      Rayleigh-equation-streamline approach increases when nonisotope-fractionating
      abiotic processes cause a significant decrease in contaminant concentrations.

PMID- 17547199
TI  - n-alkane profiles of engine lubricating oil and particulate matter by molecular
      sieve extraction.
AB  - As part of the Canadian Atmospheric Fine Particle Research Program to obtain
      reliable primary source emission profiles, a molecular sieve method was developed
      to reliably determine n-alkanes in lubricating oils, vehicle emissions, and
      mobile source dominated ambient particulate matter (PM). This work was also
      initiated to better calculate carbon preference index values (CPI: the ratio of
      the sums of odd over even n-alkanes), a parameter for estimating anthropogenic
      versus biogenic contributions in PM. n-Alkanes in lubricating oil and mobile
      source dominated PM are difficult to identify and quantify by gas chromatography
      due to the presence of similar components that cannot be fully resolved. This
      results in a hump, the unresolved complex mixture (UCM) that leads to incorrect n
      alkane concentrations and CPI values. The sieve method yielded better
      chromatography, unambiguous identification of n-alkanes and allowed examination
      of differences between n-alkane profiles in light (LDV) and heavy duty vehicle
      (HDV) lubricating oils that would have been otherwise difficult. These profile
      differences made it possible to relate the LDV profile to that of the PM samples
      collected during a tunnel study in August 2001 near Vancouver (British Columbia,
      Canada). The n-alkane PM data revealed that longer sampling times result in a
      negative artifact, i.e., the desorption of the more volatile n-alkanes from the
      filters. Furthermore, the sieve procedure yielded n-alkane data that allowed
      calculation of accurate CPI values for lubricating oils and PM samples. Finally,
      this method may prove helpful in estimating the respective diesel and gasoline
      contributions to ambient PM.

PMID- 17547200
TI  - Raman microspectroscopic analysis of changes in the chemical structure and
      reactivity of soot in a diesel exhaust aftertreatment model system.
AB  - Raman microspectroscopy has been applied to follow structural changes in spark
      discharge (GfG) soot and light-duty diesel vehicle (LDV) soot upon oxidation and
      gasification by nitrogen oxides and oxygen in a diesel exhaust aftertreatment
      model system at 523 and 573 K. Raman spectra have been recorded before and during
      the oxidation process, and spectral parameters have been determined by curve
      fitting with five bands (G, D1-D4). For GfG soot, a steep initial decrease of the
      relative intensity of the D3 band suggested rapid preferential oxidation of a
      highly reactive amorphous carbon fraction, while a less steep but also
      substantial decrease of band widths (in particular, the D1 band) indicated a
      slower overall increase of chemical homogeneity and structural order in the
      partially oxidized material. The spectroscopic changes are in agreementwith a
      strong decrease of chemical reactivity at increasing mass conversion of GfG soot.
      In contrast, the spectral parameters and reactivity of partially oxidized LDV
      soot remained largely unchanged throughout the oxidation process. Overall, the
      spectroscopic and kinetic findings suggest that Raman spectroscopic parameters
      provide information about the relative abundance and structural order of
      graphitelike and amorphous carbon and can be used as proxies for the chemical
      reactivity of soot undergoing oxidation and gasification. Thus, Raman
      spectroscopy promisesto become an efficient tool forfurther investigation and
      optimization of diesel exhaust aftertreatment in continuously regenerating traps
      and particle filters.

PMID- 17547201
TI  - Elimination of selected acidic pharmaceuticals from municipal wastewater by an
      activated sludge system and membrane bioreactors.
AB  - The elimination of six acidic pharmaceuticals (clofibric acid, diclofenac,
      ibuprofen, ketoprofen, mefenamic acid, and naproxen) in a real wastewater
      treatment plant (WWTP) using an activated sludge system and membrane bioreactors
      (MBRs) was investigated by using a gas chromatography/mass spectrometry (GC/MS)
      system for measurement of the compounds. Limited information is available for
      some of the tested pharmaceuticals at present. Solid retention times (SRTs) of
      the WWTP and the two MBRs were 7, 15, and 65 days, respectively. The elimination
      rates varied from compound to compound. The MBRs exhibited greater elimination
      rates for the examined pharmaceuticals than did the real plant. Dependency of the
      elimination rates of the pharmaceuticals on SRTs was obvious; the MBR operated
      with a longer SRT of 65 days clearly showed better performance than did the MBR
      with a shorter SRT of 15 days. The difference between the two MBRs was
      particularly significant in terms of elimination of ketoprofen and diclofenac.
      Measurements of the amounts of adsorbed pharmaceuticals on the sludge and aerobic
      batch elimination experiments were carried out to investigate the elimination
      pathways of the pharmaceuticals. Results of the batch elimination tests revealed
      that the sludges in the MBRs had large specific sorption capacities mainly due to
      their large specific surface areas. Despite the sorption capacities of sludges,
      the main mechanism of elimination of the pharmaceuticals in the investigated
      processes was found to be biodegradation. Biodegradation of diclofenac, which has
      been believed to be refractory to biodegradation, seemed to occur very slowly.

PMID- 17547202
TI  - Tobacco waste/industrial sludge based desulfurization adsorbents: effect of phase
      interactions during pyrolysis on surface activity.
AB  - Industrial waste derived adsorbents were obtained by pyrolysis of tobacco waste
      with either metal sludge or waste oil sludge from a shipyard. The materials were
      used as media to remove hydrogen sulfide at room temperature in the presence of
      moisture. The initial and exhausted adsorbents after the breakthrough tests were
      characterized using sorption of nitrogen, thermal analysis, XRD, elemental
      analysis, and surface pH measurements. It was found that mixing tobacco and
      industrial sludges results in a strong synergy, enhancing the catalytic
      properties of adsorbents. This synergy is observed in both surface chemistry and
      porosity. During pyrolysis, new mineral phases are formed as a result of solid
      state reactions between the components of the sludges. They are highly dispersed
      on the surface of mesopores. A high volume of these pores is a result of
      activation of the carbon phase in the composite by alkaline earth metals and also
      by the release of water from the decomposition of an inorganic phase that is in
      the predominant quantity. A high temperature of pyrolysis is beneficial for the
      adsorbents due to the enhanced activation of the carbonaceous phase and the
      chemical stabilization of the inorganic phase. Samples obtained at low
      temperatures are sensitive to water, which deactivates their catalytic centers.

PMID- 17547203
TI  - Enhanced corrosion-based Pd/Mg bimetallic systems for dechlorination of PCBs.
AB  - Polychlorinated biphenyls (PCBs) are toxic pollutants notorious for their aquatic
      and sedimentary prevalence and recalcitrant nature. Bimetallic systems like Pd/Fe
      have been widely studied for degrading them. Mg, with oxidation potential higher
      than Fe, has been reported to dechlorinate PCBs in conjunction with K2PdCl6
      systems that are distinct from Pd/Mg bimetals. This study primarily aims to
      evaluate Pd/Mg bimetallic systems for dechlorinating 2-chlorobiphenyl (2-CIBP), a
      model PCB. Candidacy of Mg is based on its unique corrosion properties that
      afford synthesis and storage under ambient conditions and application-based
      advantages. A simple wet-chemistry procedure was developed to synthesize Pd/Mg
      particles with 0.11-1.62% Pd content and nanoscale Pd-islands as determined by X
      ray diffraction (XRD) and environmental scanning electron microscopy (ESEM).
      Aqueous 2-CIBP matrices were effectively degraded using these particles, the
      dechlorination kinetics showing linear dependence on the total Pd content. The pH
      profile obtained with varying bimetallic content led to useful insights into the
      unique behavior of Mg surface. A carbon mole balance showed 85-105% recoveries.
      Performance of the Pd/Mg particles in PCB spiked clays and sediment suggests that
      they may work well in such systems. Finally, a mechanism for PCB dechlorination
      in Pd/Mg systems was proposed.

PMID- 17547204
TI  - Sunlight-induced photochemical decay of oxidants in natural waters: implications
      in ballast water treatment.
AB  - The transport and discharge of ship ballast water has been recognized as a major
      vector for the introduction of invasive species. Chemical oxidants, long used in
      drinking water and wastewater treatment, are alternative treatment methods for
      the control of invasive species currently being tested for use on ships. One
      concern when a ballasted vessel arrives in port is the adverse effects of
      residual oxidant in the treated water. The most common oxidants include chlorine
      (HOCl/OCl-), bromine (HOBr/OBr-), ozone (03), hydrogen peroxide (H2O2), chlorine
      dioxide (ClO2), and monochloramine (NH2Cl). The present study was undertaken to
      evaluate the sunlight-mediated photochemical decomposition of these oxidants.
      Sunlight photodecomposition was measured at various pH using either distilled
      water or oligotrophic Gulf Stream water for specific oxidants. For selected
      oxidants, quantum yields at specific wavelengths were obtained. An environmental
      photochemical model, GCSOLAR, also provided predictions of the fate (sunlight
      photolysis half-lives) of HOCI/OCl-, HOBr/OBr-, ClO2, and NH2Cl for two different
      seasons at latitude 40 degrees and in water with two different concentrations of
      chromophoric dissolved organic matter. These data are useful in assessing the
      environmental fate of ballast water treatment oxidants if they were to be
      discharged in port.

PMID- 17547205
TI  - Influence of the oxidizing species on the reactivity of iron-based Bimetallic
      reductants.
AB  - Anticipating which pollutants are amenable to treatment by iron-based bimetallic
      reductants requires an understanding of the mechanism(s) driving pollutant
      reduction. Here, batch studies with six bimetals (Au/Fe, Co/Fe, Cu/Fe, Ni/ Fe,
      Pd/Fe, and Pt/Fe) and four oxidants (alkyl polyhalides, vinyl polyhalides,
      alkynes, and water) explored the influence of the electron acceptor on reductant
      reactivity. Bimetals exhibited disparate reactivity toward some oxidant classes.
      For example, Pt/Fe enhanced rates of cis-dichloroethylene reduction, but it
      inhibited the reduction of several alkyl polyhalides. Moreover, the rate increase
      for vinyl polyhalide reduction by Ni/Fe (approximately 100-fold) and Pd/Fe
      (approximately 1000-fold) was far greater than that measured for alkyl
      polyhalides (approximately 10-fold), and reactivity toward vinyl polyhalides
      exhibited a more pronounced dependence on Ni and Pd loadings than did reactivity
      toward alkyl polyhalides. These results suggest that the reactions of alkyl and
      vinyl polyhalides with iron-based bimetals involve different active reductants.
      Neither rates of alkyl nor vinyl polyhalide reduction correlated with rates of
      iron corrosion by water, contrary to expectations if galvanic corrosion was
      primarily responsible for organohalide reduction. Trends observed for the
      hydrogenation of 2-butyne did mirror the sequence we identified for 1,1,1
      trichloroethane reduction, consistent with a role for atomic hydrogen as the
      principal electron donor in these two systems.

PMID- 17547206
TI  - Different catalytic effects by copper and chromium on the formation and
      degradation of chlorinated aromatic compounds in fly ash.
AB  - Fly ash from municipal solid waste incineration may catalytically enhance the
      formation and degradation of chlorinated aromatic compounds. The activities of
      three Deacon catalysts in this process were investigated in a statistically
      designed experiment. Chlorides of copper, chromium, and nickel were added to fly
      ash samples and the resulting samples heated at 300 degrees C for 2 h in an air
      atmosphere. The addition of copper increases the formation of all chlorinated
      aromatic compounds except the low chlorinated congeners of polychlorinated
      dibenzo-p-dioxins and dibenzofurans. The addition of chromium decreased the
      formation of most chlorinated aromatic compounds except the highest chlorinated
      species, where it was without effect. The addition of nickel did not show any
      significant effect. The outcome of the experiment can be interpreted as two
      competing processes: the chlorination of aromatic rings and the oxidation of
      carbon-carbon and carbon-oxygen bonds. The delicate balance between chlorination
      and oxidation could probably be further exploited to minimize both the emissions
      and the net production of chlorinated aromatic compounds from combustion.

PMID- 17547207
TI  - FeCl3/NaNO2: an efficient photocatalyst for the degradation of aquatic steroid
      estrogens under natural light irradiation.
AB  - Assistance and acceleration of the environment's self-remediation of pollutants
      represent an important and long-standing goal for environmental chemistry
      communities. Here, a degradation route using a combination of a nitrite and a
      ferric salt as the photocatalyst is presented for catalytically removing 17beta
      estradiol (E2), estriol (E3), and 17alpha-ethynylestradiol (EE2) in water under
      mimicked natural environmental conditions, i.e., in the phytotron. After a 1 day
      reaction, 86.6% of the estrogen E2 was degraded. Extending the incubation time to
      30 days, more than 99.9% E2 was removed and a very small quantity of malonic acid
      observed as the residual organic compound, and estrogenic activity was
      determined. The results showed that the estrogenic activities of the intermediate
      products are negligible and that there is no secondary risk associated with
      increased the estrogenic activity. The degradation system demonstrated that
      FeCl3/NaN02 is an efficient photocatalyst which is active on natural light
      irradiation. This work highlights a promising development for in situ treatment
      of pollutants in natural-environment conditions.

PMID- 17547208
TI  - Effect of methanol on pH and stability of inorganic biofilters treating dimethyl
      sulfide.
AB  - The biofiltration of dimethyl sulfide (DMS) and other reduced sulfur compounds
      (RSC) results in acidification of biofilters due to the accumulation of the
      sulfuric acid in packing material. This may lead to a decrease in biofilter
      performance due to a drop in pH. Results obtained from continuous experiments
      using three bench-scale biofilters packed with inorganic material mixed with
      limestone show that methanol (MeOH) alleviates the pH drop and enhances the
      stability of biofilter performance and DMS removal. The pH drop in the biofilters
      treating DMS with MeOH is 4 fold slower than that in the control biofiler
      treating DMS only. For the biofilters with MeOH addition, the pH of the
      biofilters drops more gradually (0.044 pH units per day) when compared to the
      MeOH suspension periods when MeOH is not added (0.23 pH units per day). MeOH
      addition consumes oxygen and results in a lower conversion ratio of sulfide to
      sulfuric acid due to the formation of elemental sulfur, reducing acidification in
      the biofilters. Nitrification was found to be actively taking place in the
      control biofilter treating DMS without MeOH addition, contributing to the
      significant pH drop in the reactor. It is proposed that MeOH prevents acid
      production from nitrification likely by limiting oxygen and nutrients to
      nitrifying bacteria in the MeOH-fed biofilters.

PMID- 17547209
TI  - Catalytic ammonia decomposition over industrial-waste-supported Ru catalysts.
AB  - Industrial solid wastes (fly ash and red mud) have been employed as supports for
      preparation of Ru-based catalysts. Physical and chemical treatments on red mud
      were conducted and these modified supports were also used for preparation of Ru
      based catalysts. Those Ru catalysts were characterized by various techniques such
      as N2 adsorption, H2 adsorption, XRD, XPS, and temperature-programmed reduction
      (TPR), and were then tested for catalytic ammonia decomposition to hydrogen. It
      was found that red-mud-supported Ru catalyst exhibits higher ammonia conversion
      and hydrogen production than fly-ash-supported catalyst. Heat and chemical
      treatments of the red mud greatly improve the catalytic activity. Moreover, a
      combination of acid and heat treatments produces the highest catalytic conversion
      of ammonia.

PMID- 17547210
TI  - Hyperbranched poly(epsilon-caprolactone) as a nonmigrating alternative
      plasticizer for phthalates in flexible PVC.
AB  - Hyperbranched (dendritic) poly(epsilon-caprolactone)s (HPCLs) were synthesized to
      have architectural variations, which are the different lengths of linear segments
      and different numbers of branches, and were used as plasticizers for flexible
      poly(vinyl chloride) (PVC). The plasticization efficiency estimated by the
      lowering of glass transition temperature and the enhancement in ultimate
      elongation indicated that the HPCLs with the shorter linear segments and the
      larger number of branches imparted as high flexibility as di(ethylhexyl)
      phthalate (DEHP) and much higher flexibility than their linear analogue, linear
      poly(epsilon-caprolactone), which is one of currently used polymer plasticizers.
      Volatility, extractability, and exudation tests for PVC/HPCL samples showed that
      there was no plasticizer migration even at very harsh condition, while ca. 7-78%
      of additives in PVC/DEHP was migrated out of samples, indicating that the HPCL
      can be used as an alternative plasticizer to remove the potential health risk
      from migrating phthalates during end use.

PMID- 17547211
TI  - Classification of heavy-metal toxicity by human DNA microarray analysis.
AB  - Microarray technology is proving to be a useful tool to classify undefined
      environmental toxicants, to investigate underlying mechanisms of toxicity, and to
      identify candidate toxicant-specific genetic markers by examining global effects
      of putative toxicants on gene expression profiles. The aim of this study was to
      evaluate the toxicities of six heavy metals through the comparison with gene
      expression patterns induced by well-known chemicals. For this purpose, we first
      identified the genes altered specifically in HepG2 under the exposure of 2,3
      dimethoxy-1,4-naphthoquinone (DMNQ), phenol, and N-nitrosodimethylamine (DMN),
      which were selected as the model chemicals, using DNA microarray. On the basis of
      the expression profiles of these genes, toxicities of six heavy metals, arsenic,
      cadmium, nickel, antimony, mercury, and chromium, were evaluated. The specific
      gene alteration and hierarchical clustering revealed that biological action of
      six heavy metals was clearly related to that of DMNQ which has been reported to
      be a reactive oxygen species (ROS) generating chemical and which induced the
      genes associated with cell proliferative responses. These results suggest that
      cell proliferative responses which are probably caused by ROS are a major
      apparent biological action of high-dose heavy metals, supporting the previous
      reports. Overall, a mechanism-based classification by DNA microarray would be an
      efficient method for evaluation of toxicities of environmental samples.

PMID- 17547212
TI  - Aryl hydrocarbon receptor plays a significant role in mediating airborne
      particulate-induced carcinogenesis in mice.
AB  - Urban particulate air pollution is associated with an increased incidence of
      cancers, and especially lung cancer. Organic extracts of airborne particulate
      matter (APM) cause cancer in mice, and PAHs adsorbed to APM are associated with
      particle-induced carcinogenesis. PAHs are agonists for AhR and are predominantly
      responsible for lung cancer through induction of highly carcinogenic metabolites.
      PAH metabolization requires CYP1A1 induction through activation of AhR, and
      therefore we hypothesized that carcinogenesis due to PAHs in APM would be reduced
      in AhR-/- mice. To examine this hypothesis, we performed a long-term continuous
      application study of carcinogenesis in AhR-/- mice using airborne particulate
      extract (APE) of APM collected in Sapporo. Tumor development (squamous cell
      carcinoma) occurred in 8 of 17 AhR+/+ mice (47%), but no tumors were found in AhR
      /-mice, and CYP1A1 was induced in AhR+/+ mice but not in AhR-/- mice. These
      results demonstrate that AhR plays a significant role in APE-induced
      carcinogenesis in AhR+/+ mice and CYP1A1 activation of carcinogenic PAHs is also
      of importance. Therefore, measurement of CYP1A1 induction in vitro may be useful
      for assessment of APM-induced carcinogenesis in humans. We also show that PAH
      like compounds are major contributors to AhR-mediated carcinogenesis, whereas
      TCDD and related compounds make a smaller contribution.

PMID- 17547213
TI  - Impact of surface water conditions on preservative leaching and aquatic toxicity
      from treated wood products.
AB  - New alternative wood preservatives contain higher levels of copper (Cu) which can
      promote aquatic toxicity in natural water systems. Earlier work focused on
      evaluating toxicity using laboratory generated leaching solutions. In this study,
      the impact on preservative leaching and aquatic toxicity from treated wood
      products was evaluated using natural surface waters including waters from two
      rivers, three lakes, two wetlands, and one seawater, in addition to synthetic
      moderate hard water and deionized water. Blocks of wood treated with Cu based
      alternatives such as alkaline copper quaternary (ACQ) and copper boron azole
      (CBA), along with chromated copper arsenate (CCA)-treated wood, were leached
      under quiescent conditions, and total Cu, labile Cu, and heavy metal toxicity
      were measured. Results show that ACQ- and CBA-treated wood leach approximately 10
      and 20 times more total Cu relative to CCA-treated wood and that the presence of
      organic and inorganic ligands in natural waters lowered the labile fraction of Cu
      relative to that from laboratory generated leaching solutions. Aquatic toxicity
      was found to correlate with the labile Cu fraction, and hence, the aquatic
      toxicity of the treated wood leachates was lower in natural waters in comparison
      to laboratory leaching solutions. The results of the present study suggest that
      studies designed to evaluate the impacts of treated wood should therefore
      consider the role of complexation in reducing the labile Cu fraction and its
      potential role in decreasing toxicity.

PMID- 17547214
TI  - [Rubella epidemiology in Italy in years 1998-2004].
AB  - In November 2003 the National Plan for the elimination of measles and congenital
      rubella was approved, with the aim of reducing and maintaining the incidence of
      congenital rubella syndrome (CRS) at less than 1 case per 100,000 live births by
      2007. In order to describe the epidemiology of rubella in Italy, we conducted a
      serosurvey and evaluated incidence and vaccination coverage data available for
      the period 1998-2004. In the years considered, national mean coverage of measles
      mumps-rubella vaccination within the second year of life, even though still below
      the 95% threshold, has progressively increased reaching 87%. In addition,
      previously existing differences in coverage among regions have diminished. In the
      same period the incidence of rubella has decreased, with a historic minimum of
      461 cases notified in 2004. The cyclic pattern typical of rubella persists, but
      with a prolongation of the interepidemic period and an increased mean age of
      acquisition of the infection. Although the proportion of immune individuals has
      increased, the percentage of women of childbearing age susceptible to rubella
      remains high (11% in the 15-19 year age group and 8% in the 20-39 year age group)
      and CRS cases continue to occur. Despite the clear results achieved through the
      implementation of vaccination strategies in children within the second year of
      life, a continued strong public health commitment is required to increase the
      proportion of vaccinated individuals and absolute priority must be given to
      immunising women of childbearing age.

PMID- 17547215
TI  - [Physicians working at the NHS Prevention Department: a national survey in
      Italy].
AB  - In Italy NHS Prevention Departments (PDs) are central in Public Health (PH)
      management. Objective was to describe profile of Medical Doctors (MDs) working at
      Italian PDs. The study, part of another survey, was conducted in 2003, using a
      phone questionnaire to administer to a sample of Italian MDs in PH. Response rate
      was 72.3% (603/833). Physicians of PDs were 255, 42.3% of whole sample. Job
      satisfaction mean (scale: 0-100) was 66.6 (SD = 19.3). 81.6% (208/225) of MDs
      said that Regions must monitor health status to identify collective risks and
      problems, while 77.3% (197/255) of them answered that function of State is to
      develop politics and planes to pursue individual and collective health. The study
      gives a positive frame of MDs at PDs. They were satisfied and persuaded of
      importance of State and Regions in PH management.

PMID- 17547216
TI  - Is an institution-wide programme able to reduce the in-patients' experiences of
      pain in a high specialization hospital?
AB  - The study examines the implication of an institution-wide programme on pain
      management in reducing the patients' perception of the pain carried out in a
      university hospital by comparing the results of two surveys conducted in 2002
      (prior to the programme) and in 2003 (during the course of the programme). The
      study was conducted in November 2003 and it consisted in a priority survey on the
      patients' pain perception using a questionnaire which was distributed to all the
      patients admitted in a highly specialised hospital and interviewed by trained
      interviewers. Later on the data were compared to the results obtained with a
      similar survey carried out in November 2002 in the same hospital. In 2002 the
      percentage of patients reporting pain at the moment of the interview was 43.4%
      (82/145), in the year 2003 it was 35.3% (49/139) [OR = 2.4, CI (95%) = 1.4-4.0, p
      < 0.001]. With regards to the pain reported in the previous 24 hrs, there was a
      reduction in the percentage of patients experiencing pain from 69.0% in 2002
      (100/145) to 42.4% in 2003 (59/139) [OR = 3.0, CI (95%) = 1.8-5.0, p < 0.001].
      Our hospital wide program succeeded in reducing pain in patients, improving
      professional quality and creating customer satisfaction in a hospital.

PMID- 17547217
TI  - [Customer satisfaction in home care: methodological issues based on a survey
      carried out in Lazio].
AB  - Home care customer satisfaction has been, until now, rarely evaluated. After
      illustrating the main italian regional surveys on this issue, the article
      presents a customer satisfaction survey carried out in the district of
      Civitavecchia (Local Health Unit 'Rome F'), Lazio, regarding 30 home care
      beneficiaries. Methodological aspects emerging from the survey are basically
      focused on: advantages and disadvantages of quantitative and qualitative
      approaches (possibly associated each other); main criteria of eligibility of
      people selected for interviewing, both patients or caregivers; conditions that
      maximize answers reliability, including training on interviewers. Authors
      highlight opportunity of using such kind of survey, integrated with other
      different tools, into a systemic vision, for promoting management changes coming
      from suggested problems, aimed at total quality management.

PMID- 17547218
TI  - [Home care for patients with ictus cerebri. An observational study in the
      metropolitan area of Milano].
AB  - Health care assessment is a very relevant process in health services
      organization. Despite home care appears to be a very important tool in health
      care delivery system, its impact has been only rarely evaluated in this country.
      The observational study we performed in the ASL Citta di Milano on patients
      affected by ictus cerebri was aimed at addressing some questions in order to
      assess whether services can be delivered more cost effectively. We chose to look
      mainly at the effectiveness and cost of services for the people in need and their
      caregivers selected in two years time. The results are showed according to
      different patients' profiles and precocity of recruitment. Their analysis shows
      that further improvements can still be made in order to achieve a better tailored
      profile of delivery. Moreover it can be seen how the burden of costs still falls
      largely on families and caregivers. The study can be seen as premises for further
      analyses as well as a follow up intervention.

PMID- 17547219
TI  - [Societal cost of pre-lingual deafness].
AB  - Congenital hearing loss still remain an important medical and social problem for
      the delayed language development. Object of this study is to provide an updated
      and close estimate of the economic burden involved in pre-lingual hearing loss.
      Data were provided by the Ministry of Health data bank, the Ministry of Education
      national data bank, the National Institute of Social Insurance national data bank
      and the Italian Central Statistics Institute. The information was collected by
      means of a specially provided Societal Cost Questionnaire (SCQ). Direct medical
      costs, direct non-medical costs and indirect welfare costs involved in deafness
      were included in the cost estimate. Was enrolled in the study a sample of
      subjects with pre-lingual deafness, with a mean bilateral neuro-sensorial hearing
      impairment equal to 60 dB or more for 500, 1,000 and 2,000 Hz frequency tones in
      the better ear detected in neonatal age, had prevented speech from developing.
      The statistical assessment was performed according to an actuarial approach,
      considering the estimated life expectancy at birth, based on updated population
      data from census 2001. Based on life expectancy, the lifetime mean cost assessed
      for a subject affected by profound pre-lingual deafness turned out to be equal to
      Euro 737,994.76 for a male and Euro 755,404.02 for a female. Unlike other
      disabling affections, deafness weighs significantly more on the social system
      than on the health system. As a matter of fact, the direct medical costs, such as
      audiological diagnosis, hearing aids, etc., only account for 3.8% of the societal
      cost, whereas education, rehabilitation and welfare costs reach 96.2% of the
      total. Finally, our results suggest that societal costs can only be reduced by
      zeroing in on promotion and broadening of effective prevention strategies. The
      appropriate public health measures (such as the universal newborn hearing
      screening) set up and implemented in several European and non-European countries
      proved effective and reduced the handicap degree resulting from deafness. The
      investment in prevention will be widely paid.

PMID- 17547220
TI  - Access to and quality of health and social care for rare diseases: patients' and
      caregivers' experiences.
AB  - People suffering from rare diseases, independently of the condition, often
      experience the same problems in receiving adequate health and social care. It is
      not clear how these problems differ in severity among different diseases and in
      different countries and how they change in time. In the framework of the NEPHIRD
      (Network of Public Health Institutions on Rare Diseases), a European project,
      funded by DG-SANCO (EU Commission), an effort was made to develop a simple but
      comprehensive tool to show patients' and/or caregivers' opinions about the
      quality and accessibility of health and social services. The self-filled
      questionnaire asks how often patients or caregivers had both negative and
      positive experiences about the quality and accessibility of health and social
      services and their opinion on their improvement, on 5-level scales. A pilot
      survey was carried out in several European Countries among members of Myasthenia
      Gravis, Neurofibromatosis, Prader Willi and Rett Syndrome volunteers'
      associations. Descriptive and comparative analyses were performed using Stata and
      Epi Info 2000. In total, 302 questionnaires were completed in France, Italy,
      Romania, Spain, Turkey and United Kingdom during 2004-05. In general, respondents
      thought that health care accessibility was worse than quality, and that social
      care and legal provisions were worse than health care, with some differences
      among countries. For all diseases, and for both patients and caregivers, the most
      frequent reported positive experiences were health professionals' kindness and
      readiness to help (all medians ranged from 3 to 5). As for the efforts for
      improvement made by public services in the last three years, the opinions were
      generally favourable. This study has several limitations. However the assessment
      tool that has been developed has some innovative and interesting features and may
      be considered a useful attempt to compare patients' and caregivers' experiences
      for a range of different diseases, countries and services, with respect to a rare
      disease programme.

PMID- 17547221
TI  - A pilot survey of child restraint and seating position in cars in Florence Health
      Authority area.
AB  - To investigate the use of child restraint and seating position in Florence, in
      the Centre of Italy, after the introduction of the New Italian road traffic law,
      a survey has been conducted. Direct observations were made in the areas related
      to three schools attended by children of different age groups, to determine the
      presence of child car seats and their positioning as well as child positioning in
      case of absence of the seat. A total of 328 vehicles have been observed; in 48.5%
      of the cars, seats for children were present, 39% were used, and 9% were not
      used. The presence of child restraint and its use differed according to age,
      school opening and closing time and number of children on board. When restraints
      were not present, children were mostly (38%) located on the front seat without an
      accompanying adult. Child seats were prevalently located in the rear. In spite of
      the introduction of New Italian road traffic law, in the study area the modality
      of children's transport in cars was frequently not correct, which constitutes a
      risk for the health of this specific target group.

PMID- 17547222
TI  - [Protection of the environment, protection of health. Note 2--Monitoring of flood
      environments: comparison of the results of the different methods and hygienic
      evaluations].
AB  - The authors take into consideration the results obtained from the application of
      the different methods and systems of river monitoring (E.B.I, Law 152/99, I.F.F),
      and they evaluate the agreement of the final judgment. The comparative analysis
      is conducted pointing out the conceptual and methodological differences of the
      three systems of the river monitoring. A good agreement of judgement arises from
      the correlation.

PMID- 17547223
TI  - A call for renewed research on tick-borne Francisella tularensis in the Arkansas
      Missouri primary national focus of tularemia in humans.
AB  - Arkansas-Missouri has emerged as the primary U.S. focus of tularemia, which is
      caused by the National Institute of Allergy and Infectious Diseases Category A
      Priority Pathogen Francisella tularensis, over the past 30 yr. There are several
      pieces of indirect evidence suggesting that a key role of ticks in the
      transmission of F. tularensis to humans in Arkansas-Missouri is the primary
      reason why tularemia has remained a prominent disease of humans in this two-state
      area while fading away from other central or eastern states after a general
      decline in rabbit-associated tularemia cases. The primary tick vector(s) in
      Arkansas-Missouri can, based on a comparison of seasonal patterns of human
      tularemia cases and peak host-seeking activity of commonly human-biting tick
      species and life stages, be narrowed down to Amblyomma americanum (L.) nymphs, A.
      americanum adults, or Dermacentor variabilis (Say) adults. Unfortunately,
      currently available data cannot be used to further elucidate the relative roles
      of these ticks as vectors of F. tularensis to humans in Arkansas-Missouri. To
      address the fact that we do not know which tick species is the primary vector of
      F. tularensis to humans in the most prominent U.S. focus of tularemia, we need to
      determine (1) relative contributions of different tick species and life stages as
      human biters in Arkansas-Missouri; (2) natural rates of infection with F.
      tularensis tularensis (type A) and F. tularensis holarctica (type B) of the most
      prominent human-biting ticks in areas of Arkansas-Missouri hyperendemic for
      tularemia; (3) experimental vector efficiency of these ticks for both F.
      tularensis tularensis and F. tularensis holarctica; and (4) presence of infection
      with F. tularensis tularensis or F tularensis holarctica in ticks collected from
      humans in Arkansas-Missouri.

PMID- 17547224
TI  - Salivary glands of second and third instars of Dermatobia hominis (Diptera:
      Oestridae).
AB  - Salivary glands of Dermatobia hominis (L., Jr.) (Diptera: Oestridae) larvae were
      studied under light and electron microscopy. The salivary glands of second (L2)
      and third instars (L3) are similar and consist of pairs of translucent tubules.
      The individual efferent ducts unite to form a single deferent duct, which inserts
      dorsally into the cephalopharingeal skeleton. Each gland has a monolayer of
      epithelial cells surrounded by basement membrane and connective tissue. The
      cellular plasma membrane is enfolded at its base, forming a labyrinthine area.
      The cell surface is linked to the basement membrane (BM) by hemidesmosomes and to
      adjacent cells by septet junctions and desmosomes. Irregular channels with
      several vesicles occur between the cytoplasm and BM. Golgi complex, rough and
      smooth endoplasmic reticulum, ribosome, lysosomes, multivesicular bodies, and
      myelin figures are usually present in the cells. The nucleus is large, with
      diffuse chromatin. The connective tissue circling the BM contains collagen
      fibrils, muscle fibers and tracheal tubes. Lined cuticle encloses the efferent
      and deferent ductal cells, which have few, widely dispersed mitochondria, free
      ribosomes, microtubules, and a large nucleus with diffuse chromatin.

PMID- 17547225
TI  - Revision of the genus Andreacarus (Acari: Laelapidae) with description of seven
      new species and a new genus for Australian species formerly placed in
      Andreacarus.
AB  - The mesostigmatid genus Andreacarus Radford, 1953 (Acari: Laelapidae), species of
      which are obligatory parasites of small mammals, is revised. Andreacarus includes
      11 species, four species previously recognized and seven new species described
      from Madagascar hosts: A. brachyuromys sp. n. from Brachyuromys betsileoensis
      Bartlett, A. eliurus sp. n. from Eliurus species, A. gymnuromys sp. n. from
      Gymnuromys roberti Major, A. voalavo sp. n. from Voalavo gymnocaudus Carleton &
      Goodman, A. nesomys sp. n. from Nesomys rufus Peters-all from nesomyid rodents;
      A. tenrec sp. n. from Tenrec ecaudatus Schreber (Afrosoricida: Tenrecidae); and
      A. galidia from Galidia elegans I. Geoffroy Saint-Hilaire (Carnivora:
      Viverridae). An amended generic diagnosis and key to females are also given. Six
      species described in Andreacarus from Australian and New Guinean hosts are
      removed and transferred to the new genus, Juxtalaelaps.

PMID- 17547226
TI  - Age and body size influence male sperm capacity of the dengue vector Aedes
      aegypti (Diptera: Culicidae).
AB  - Understanding mosquito mating biology is essential for studies of mosquito
      behavior, gene flow, population structure, and genetic control. In the current
      study, we examine the effect of age and body size on spermatozoa number in two
      laboratory strains of the dengue vector, Aedes aegypti (L.), Thailand and
      Rockefeller (ROCK), and in wild-collected mosquitoes from Thailand. Body size was
      a major predictor of total spermatozoa number, with significantly greater sperm
      numbers in large (2.27-mm wing length) versus small males (1.85-mm wing length)
      within the same age group. Total sperm capacity also varied by male age.
      Spermatozoa numbers in virgin Ae. aegypti males increased significantly up to 10
      d after emergence and then leveled off until 20 d. Significant variations in
      sperm number were detected among Ae. aegypti strains, with wild-collected
      mosquitoes having the greatest total number of sperm. Our study provides the
      first evidence of spermatogenesis in adult mosquitoes and indicates high rates of
      spermatogenesis in male mosquitoes up to 10 d of age (3.3 degree-days). Our
      results emphasize the potential role of body size and age on the mating capacity
      of this important vector of dengue and yellow fever viruses.

PMID- 17547227
TI  - Comparative laboratory study on the reaction of Aedes aegypti and Aedes
      albopictus to different attractive cues in a mosquito trap.
AB  - The behavioral responses of Aedes aegypti (L.) and Aedes albopictus (Skuse)
      adults to several attractive cues, as reactions to mosquito traps, are compared
      in the laboratory, and differences in the primary attractive factors for both
      species are discussed. Target-attacking frequency of unfed Ae. aegypti females
      was >30 times that of unfed Ae. albopictus females under simulated conditions.
      Changes in the percentage of trapped mosquitoes under several attractive
      conditions using commercial mosquito traps showed that Ae. aegypti mosquitoes
      were trapped 2-3 times faster than Ae. albopictus. For Ae. aegypti, the
      combination of a visual cue + CO, alone enhanced attractiveness, whereas both a
      visual cue + CO, as well as a visual cue + octenol enhanced Ae. albopictus. The
      combination of at least three factors, such as a visual cue, CO2, and a chemical
      cue is thought to be valuable for trapping and estimating the relative adult
      population sizes of Ae. aegypti and Ae. albopictus

PMID- 17547228
TI  - Genetic structure and gene flow along an altitudinal gradient among two
      stomoxyine species (Diptera: Muscidae) on La Reunion Island.
AB  - Seasonal variations of insect population sizes are often dramatic, particularly
      in temperate regions and at altitudes where the climatic conditions are
      unfavorable to insect development during the winter. Decline of population size
      (or bottlenecks) and founder events may reduce the genetic variability and may
      create genetic differentiation between populations by drift and founder effects,
      but this reduction of genetic diversity is strongly influenced by gene flow
      between populations. In this study, we determined the population genetic
      structure for two stomoxyine species (Diptera: Muscidae), Stomoxys calcitrans
      (L.) and Stomoxys niger niger Macquart, which co-occur in dairy barns along an
      altitudinal gradient on La Reunion island. Using microsatellite markers, we
      quantified the genetic variation within and among populations for different
      altitudes. This study displays that, contrary to expectations, genetic diversity
      is not correlated with altitude and that genetic differentiation is not larger
      among high-altitude populations than among low-altitude populations. These
      results attest to the small drift and founder effects in high-altitude
      populations despite drastic decreases in population size during the winter.
      Furthermore, at the island scale, the populations of S. calcitrans were slightly
      differentiated, but those of S. niger niger were not. Together, the results
      revealed large levels of gene flow on La Reunion Island despite the dramatic
      geographic barriers, and they emphasize the importance of considering
      agricultural practices to restrict the dispersal of stomoxyines.

PMID- 17547229
TI  - Isolation and partial characterization of proteins with vasodegenerative and
      proinflammatory properties from the egg-nests of Hylesia metabus (Lepidoptera:
      Saturniidae).
AB  - The Hylesia genus comprises a group of Neotropical moths ubiquitous in the
      Americas from Arizona to Argentina. One of the species of the Hylesia genus in
      Venezuela, French Guyana, and Trinidad has been identified as Hylesia metabus
      (Cramer 1775) (Lepidoptera: Saturniidae). In Venezuela, these moths are found in
      abundance in the mangrove (Avicennia spp.) swamps surrounding the Gulf of Paria
      and the Orinoco Delta in the eastern part of the country. During the mating
      season, the female adults shed copious amounts of urticating setae in the air,
      producing a severe papulovesicular dermatitis among the population in the
      affected areas. The females also use their urticating setae to protect the eggs
      during the hatching period. In the current study, we have isolated and partially
      characterized proteins with proinflammatory properties from the urticating setae
      in the egg-nests by using sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis and anionic exchange-high-performance liquid chromatography
      (HPLC). We also have studied the biological response of the egg-nest extract and
      the HPLC purified fractions by inoculation in guinea pigs; and, analyzing the
      tissue samples by means of histopathological methods. The results of this study
      show that the extracted venom and HPLC purified subcomponents give rise to an
      intense inflammatory reaction characterized by massive infiltration of
      inflammatory cells, echymoses, and vascular degeneration. Chromatographic
      separation showed that the venom was made up of proteins having selectively
      vasodegenerative-fibrinolytic or proinflammatory-quimotactic properties.

PMID- 17547230
TI  - Cuticular hydrocarbon composition in pupal exuviae for taxonomic differentiation
      of six necrophagous flies.
AB  - Gas chromatography-mass spectrometry was used to analyze the cuticular
      hydrocarbons extracted from the pupal exuviae of six necrophagous flies:
      Aldrichina grahami (Aldrich), Chrysomya megacephala (F.), Lucilia sericata
      (Meigen), Achoetandrus rufifacies (Macquart), Boettcherisca peregrina (Robineau
      Desvoidy), and Parasarcophaga crassipalpis (Macquart). A discriminant model
      including the variables of peak 1 (tricosane), peak 7 (9-,11-,13-methyl
      pentacosane), peak 21 (11,12-;9,13-dimethyl-hexacosane), peak 24 (octocosane),
      peak 41 (7,11-dimethyl-nonacosane), peak 42 (3-methyl-nonacosane), peak 46 (2
      methyl-hentriacontane), and peak 51 (unknown) was constructed, which allowed a
      complete separation of the pupal exuviae of the six species. These results
      indicate that cuticular hydrocarbons as chemotaxonomic characters for insects of
      forensic importance are of high value and feasibility.

PMID- 17547231
TI  - Field evaluation against mosquitoes of regular and polymer-based deet
      formulations in Manitoba, Canada, with comment on methodological issues.
AB  - Studies were carried out in Manitoba, Canada, to evaluate the efficacy of three
      repellent products for protection of human subjects against mosquito bites. All
      test substances contained the active ingredient N,N-diethyl-3-methylbenzamide
      (deet); two were polymer-based creams (3M Ultrathon Insect Repellent and Morflex
      DEET Insect Repellent 30) and the third (Muskol Insect Repellent) was an alcohol
      based pump spray formulation. Application of repellent was to the forearm and
      lower legs of subjects at 0.75 or 0.83 mg deet/cm2. Exposure to mosquito attack
      was continuous, and efficacy was determined by measuring complete protection time
      (CPT). Regardless of whether delivered as a polymer cream or in alcohol, mean CPT
      was similar for the tested repellents at 623 +/- 107 to 644 +/- 163 min. By
      contrast, mean CPT for the different test subjects showed significant variation,
      ranging from 531 +/- 42 to 756 +/- 54 min. Mosquito collections from untreated
      human test subjects, Centers for Disease Control and Prevention (CDC) light traps
      and sweep-netting consisted primarily of Ochlerotatus sticticus (Meigen) and
      Aedes vexans (Meigen). Relative catch of these two species was similar for
      different sampling methods through much of the day, but not in the evening, when
      CDC light traps oversampled Ae. vexans relative to untreated human subjects.
      Results are used to highlight the need to account for intersubject variation when
      designing repellent studies, and also are used as a basis to discuss limitations
      associated with using relatively few subjects when testing repellents.

PMID- 17547232
TI  - Different amino-acid substitutions confer insecticide resistance through
      acetylcholinesterase 1 insensitivity in Culex vishnui and Culex tritaeniorhynchus
      (Diptera: Culicidae) from China.
AB  - Insecticide resistance owing to insensitive acetylcholinesterase (AChE)1 has been
      reported in several mosquito species, and only two mutations in the ace-1 gene
      have been implicated in resistance: 119S and 331W substitutions. We analyzed the
      AChE1 resistance status of Culex vishnui (Theobald) and Culex tritaeniorhynchus
      Giles sampled in various regions of China. These two species displayed distinct
      mutations leading to AChE1 insensitivity; the 119S substitution in resistant C.
      vishnui mosquitoes and the 331W substitution in resistant C. tritaeniorhynchus. A
      biochemical test was validated to detect the 331W mutation in field samples. The
      comparison of the recombinant G119S and 331W mutant proteins produced in vitro
      with the AChE1 extracted from resistant mosquitoes indicated that the AChE1
      insensitivity observed could be specifically attributed to these substitutions.
      Comparison of their biochemical characteristics indicated that the resistance
      conferred by these mutations depends on the insecticide used, regardless of its
      class. This resistance seemed to be fixed in the Cx. tritaeniorhynchus
      populations sampled in a 2000-km transect, suggesting a very high level of
      insecticide application or a low fitness cost associated with this 331W mutation.

PMID- 17547233
TI  - Efficacy of two pyrethroid insecticides applied as barrier treatments for
      managing mosquito (Diptera: Culicidae) populations in suburban residential
      properties.
AB  - Increased threat of mosquito-borne disease coupled with decreased tolerance of
      nuisance mosquitoes has opened a market for pest management professionals to
      offer mosquito control services for homeowners. A pest management professional
      applied bifenthrin (0.08%) and lambda-cyhalothrin (0.1%) at their maximum label
      concentrations as barrier treatments. We tested treatments residual efficacy in
      reducing adult mosquito populations and compared these chemicals against a water
      control at 24 residential properties (eight replications by three treatments).
      Mosquito populations were measured on each property by using five methods: CO2
      baited Centers for Disease Control (CDC) light traps (without a light), human
      landing rates, CDC gravid traps, ovitraps, and sweep nets. Populations were
      monitored weekly for 2 wk before treatment and 8 wk posttreatment. Additionally,
      to confirm residual efficacy of each insecticide, a randomly treated leaf
      underwent a no-choice bioassay with laboratory-reared Aedes albopictus (Skuse).
      Trap collections were dominantly Aedes albopictus and Culex pipiens L. Both
      insecticidal treatments significantly reduced Aedes spp. lambda-Cyhalothrin- and
      bifenthrin-treated sites had 89.5 and 85.1% fewer Ae. albopictus bites than the
      untreated control, respectively. Ae. albopictus bioassay results showed
      significant residual efficacy for both insecticides up to 6 wk posttreatment.
      There were no significant differences between properties treated with the two
      insecticides. In contrast, Culex spp. were not reduced by either insecticidal
      treatment. Our study indicated that barrier sprays applied to low-lying
      vegetation do not properly target adult daytime resting sites for Culex
      mosquitoes but that they can reduce Aedes mosquitoes. Perhaps by treating upper
      tree canopies Culex spp. abundance may be reduced.

PMID- 17547234
TI  - Transmission of bacterial agents from lone star ticks to white-tailed deer.
AB  - Amblyomma americanum (L.), the lone star tick, is an aggressive ixodid tick that
      has been implicated as a vector for several bacteria. Among these bacteria are
      the disease agents Ehrlichia chaffeensis and Ehrlichia ewingii, and the putative
      disease agent "Borrelia lonestari." The hypothesis in this study was that wild
      lone star ticks from northeastern Georgia are capable of transmitting all three
      agents to white-tailed deer, Odocoileus virginianus, a known reservoir host for
      E. chaffeensis. In this study, transmission of all three agents from wild caught
      lone star ticks to captive reared white-tailed deer was demonstrated by
      polymerase chain reaction (PCR), culture, or serology. Two of three deer showed
      evidence of E. chaffeensis and E. ewingii infection by polymerase chain reaction
      assay; all three deer showed evidence of B. lonestari by PCR assay. E.
      chaffeensis was isolated in culture from both PCR-positive deer on multiple days.
      All three deer seroconverted to E. chaffeensis, whereas one deer seroconverted to
      B. lonestari. This study supports the role of lone star ticks and white-tailed
      deer as a vector and reservoir host for E. chaffeensis and E. ewingii and
      suggests for the first time, transmission of B. lonestari from lone star ticks to
      white-tailed deer.

PMID- 17547235
TI  - Conservation of transmission phenotype of Anaplasma marginale (Rickettsiales:
      Anaplasmataceae) strains among Dermacentor and Rhipicephalus ticks (Acari:
      Ixodidae).
AB  - Before the eradication of Boophilus ticks from the United States, Rhipicephalus
      (Boophilus) microplus (Canestrini) and Rhipicephalus (Boophilus) annulatus (Say)
      were important biological vectors of the cattle pathogen Anaplasma marginale
      Theiler. In the absence of Boophilus ticks, A. marginale continues to be
      transmitted by Dermacentor ticks. However, a few U.S. strains are not
      transmissible by Dermacentor andersoni Stiles, Dermacentor variabilis (Say), or
      both, raising the question of how these strains evolved and how they are
      maintained. We hypothesize that the U.S. non-Dermacentor-transmissible strains of
      A. marginale were formerly Boophilus-transmitted strains that have been
      maintained by a combination of persistent infection and mechanical transmission
      since the eradication of their biological vector from the United States. To test
      this hypothesis, we attempted to transmit a well-documented non-Dermacentor
      transmissible A. marginale strain (Florida), by using D. andersoni and the two
      Boophilus species that formerly occurred in the United States. For comparison, we
      examined tick-borne transmission of a strain of A. marginale (Puerto Rico), which
      has previously been shown to be transmissible by both D. andersoni and B.
      microplus. All three species of tick transmitted the Puerto Rico strain, and
      immunohistochemical (IHC) analysis confirmed the presence ofA. marginale colonies
      in their salivary glands. All three tick species failed to transmit the Florida
      strain. Although both D. andersoni and B. microplus acquired transient midgut and
      salivary gland infections after acquisition feeding, we were unable to detect
      colonies of the Florida strain in the salivary glands with IHC. This demonstrates
      that the transmission phenotype ofA. marginale strains is conserved among tick
      species, and it suggests that the failure of the Florida strain to be transmitted
      by ticks is related to a general inability to efficiently invade or replicate in
      tick cells, rather than to a failure to invade or replicate in cells of a
      specific tick species.

PMID- 17547236
TI  - Survival and replication of dengue-2 virus in diapausing eggs of Aedes albopictus
      (Diptera: Culicidae).
AB  - Survival and replication of dengue-2 virus (family Flaviviridae, genus
      Flavivirus, DENV-2) was determined in diapausing eggs of Aedes albopictus (Skuse)
      (Diptera: Culicidae) to evaluate the importance of this mechanism for viral
      maintenance during adverse climatic conditions. Infected and uninfected eggs of
      Ae. albopictus were induced to diapause under low temperature and short
      photoperiod. Virus was detected by reverse transcription-polymerase chain
      reaction and isolated in C6/36 cells from both diapausing eggs and nondiapausing
      eggs. Nucleic acid hybridization was used to monitor viral replication in
      diapausing eggs. DENV-2 might survive in infected diapausing eggs in a relatively
      quiescent status based on the absence of areplicative intermediate RNA. In
      contrast, the viral replicative intermediate RNA along with the replicative form
      RNA was detected in nondiapausing eggs. It seemed that the virus replicated more
      actively in nondiapausing eggs than in diapausing eggs. Infected diapausing eggs
      may play an important role in the maintenance of DENV during adverse climatic
      conditions in nature.

PMID- 17547237
TI  - Effectiveness of permanet in Cote d'Ivoire rural areas and residual activity on a
      knockdown-resistant strain of Anopheles gambiae.
AB  - The effectiveness of long-lasting preimpregnated nets of Permanet type
      (deltamethrin, 50 mg/m2) erected in households in rural areas of Cote d'Ivoire
      was tested on two laboratory strains of Anopheles gambiae s.s.: the Kisumu
      susceptible strain and the Vk per pyrethroids resistant strain with >70% kdr
      allelic frequency. Treated nets were distributed in households in three villages
      of Danan6 forest area in western part of Cote d'Ivoire. In each village, a net
      was sampled for bioassays. Three Permanets also were erected in the laboratory,
      serving as control samples. From May 2001 to July 2002, the effectiveness of
      these deltamethrin-pretreated nets was monitored using World Health Organization
      cone tests on the two strains of An. gambiae. Mortality rates were recorded 24 h
      postexposure. Knockdown times for 50 and 95% mosquitoes (kdT50 and kdT95,
      respectively) were estimated by means of WIN DL software. One-way analysis of
      variance was used to compare the knockdown times. Times to failure of nets were
      analyzed using Cox model. The kdT50 of the Kisumu susceptible strain with both
      laboratory samples and nets used in the field varied around 10 min. No
      significant difference was recorded between the kdT50 of the Kisumu susceptible
      strain with laboratory kept nets and samples of nets used in the field. The kdT95
      values were in the same scale with the two types of nets. The kdT50 of the Vk per
      resistant strain when exposed to used nets were twofold that of the Kisumu
      susceptible strain at the beginning of the trial, and they increased to fivefold
      15 mo later. These latter kdT50 significantly differed to those of the Kisumu
      susceptible strain tested with laboratory and field samples of nets. The kdT95
      significantly differed from those of the Kisumu strain with laboratory kept nets
      and with field kept nets. Baseline bioassay mortality rates were always 99-100%
      with the Kisumu susceptible strain, and they did not show any significant
      difference between laboratory-kept nets and field-used nets during the 15-mo
      trial. With the Vk per resistant strain, the expected long-lasting activity was
      not achieved. A high decrease of mortality rates was observed from 69 to 75% in
      the first 3 mo to 2% at the month 15. This mortality was associated with
      significant differences between Vk per resistant strain tested with field-used
      nets compared with Kisumu susceptible strain tested with both laboratory kept
      nets and field-used nets. This study emphasized the actual long-lasting
      effectiveness of Permanet against the An. gambiae Kisumu susceptible reference
      strain and a rapid decrease of residual activity against a strain with kdr-based
      resistance to pyrethroids.

PMID- 17547238
TI  - Evaluation of four sampling techniques for surveillance of Culex quinquefasciatus
      (Diptera: Culicidae) and other mosquitoes in African rice agroecosystems.
AB  - Field studies were conducted in a rice, Oryza sativa L., agroecosystem in Mwea
      Kenya to compare the efficiency of CO2-baited Centers for Disease Control (CDC)
      light traps against nonbaited CDC light traps and gravid traps against
      oviposition traps in outdoor collection of Culex quinquefasciatus Say (Diptera:
      Culicidae) and other mosquitoes. Collectively, 21 mosquito species from the
      genera Culex, Anopheles, Mansonia, Ficalbia, and Aedes were captured during the
      10-wk study period. Cx. quinquefasciatus was the predominant species in all trap
      types with proportions ranging from 57% in the nonbaited CDC light traps to 95%
      in the gravid traps. Significantly higher numbers of Cx. quinquefasciatus and
      Culex annulioris Theobald were collected in the CO2-baited CDC light traps than
      in the nonbaited CDC light traps, but the numbers of other mosquito species,
      including malaria vectors Anopheles arabiensis Patton and Anopheles funestus
      Giles did not differ significantly between the two trap types. More Cx.
      quinquefasciatus females were collected in grass infusion-baited gravid traps
      than egg rafts of this species in oviposition traps containing the same infusion.
      Although most mosquitoes captured in CO,-baited and nonbaited CDC light traps
      were unfed, most of those collected in gravid traps were gravid. From these
      findings, it is concluded that at least in the rice-growing area of Mwea Kenya,
      CO2-baited CDC light traps in conjunction with gravid traps can be used in
      monitoring of Cx. quinquefasciatus both for control and disease surveillance.

PMID- 17547239
TI  - Forensically important calliphoridae (diptera) associated with pig carrion in
      rural north-central Florida.
AB  - A study to determine the relative abundance and seasonality of forensically
      important blow flies (Diptera: Calliphoridae) in rural north-central Florida was
      conducted using pig carcasses (Sus scrofa L.) as models for human bodies. Seven
      species of Calliphoridae were collected: Lucilia coeruleiviridis (=Phaenicia)
      (Macquart), Cochliomyia macellaria (F.), Chrysomya rufifaces (Macquart), Phormia
      regina (Meigen), Chrysomya megacephala (F.), and a few specimens of Calliphora
      livida Hall, and Calliphora vicina Robineau-Desvoidy. Species composition in
      aerial collections of adult flies, preserved larval collections, and samples of
      larvae reared to the adult stage were all highly correlated. Relative abundance
      of the species found was significantly different, with L. coeruleiviridis the
      most abundant species year-round. The relative abundance of the collected species
      varied significantly by day of decomposition and by season, with significant
      interactions between season and day, season and species, and day and species. L.
      coeruleiviridis, C. macellaria, C. rufifaces, and P. regina were found during the
      entire year, two C. vicina specimens and 11 C. livida specimens were collected
      from December to March, whereas C. megacephala was collected only from June
      through September.

PMID- 17547240
TI  - Thermoregulation in larval aggregations of carrion-feeding blow flies (Diptera:
      Calliphoridae).
AB  - The growth and development of carrion-feeding calliphorid (Diptera:
      Calliphoridae) larvae, or maggots, is of great interest to forensic sciences,
      especially for estimation of a postmortem interval (PMI). The development rate of
      calliphorid larvae is influenced by the temperature of their immediate
      environment. Heat generation in larval feeding aggregations (=maggot masses) is a
      well-known phenomenon, but it has not been quantitatively described. Calculated
      development rates that do not include internally generated temperatures will
      result in overestimation of PMI. Over a period of 2.5 yr, 80 pig, Sus scrofa L.,
      carcasses were placed out at study sites in north central Florida and
      northwestern Indiana. Once larval aggregations started to form, multiple internal
      and external temperatures, and weather observations were taken daily or every few
      days between 1400 and 1800 hours until pupation of the larvae. Volume of each
      aggregation was determined by measuring surface area and average depth. Live and
      preserved samples of larvae were taken for species identification. The four most
      common species collected were Lucilia coeruleiviridis (=Phaenicia) (Macquart)
      (77%), Cochliomyia macellaria (F.) (8.3%), Chrysomya rufifaces (Macquart) (7.7%),
      and Phormnia regina (Meigen) (5.5%). Statistical analyses showed that 1) volume
      of a larval mass had a strong influence on its temperature, 2) internal
      temperatures of masses on the ground were influenced by soil temperature and mass
      volume, 3) internal temperatures of masses smaller than 20 cm3 were influenced by
      ambient air temperature and mass volume, and 4) masses larger than 20 cm3 on the
      carcass had strongly regulated internal temperatures determined only by the
      volume of the mass, with larger volumes associated with higher temperatures.
      Nonsignificant factors included presence of rain or clouds, shape of the
      aggregation, weight of the carcass, species composition of the aggregation, time
      since death, or season.

PMID- 17547241
TI  - Toxicity of Myristica fagrans seed compounds against Blattella germanica
      (Dictyoptera: Blattellidae).
AB  - The insecticidal constituents of hexane-soluble fraction from a methanolic
      extract of the seeds from Myristica fragrans (Myristicaceae) against adult
      females of Blattella germanica (L.) (Dictyoptera: Blattellidae) were analyzed by
      gas chromatography and gas chromatography-mass spectrometry. The insecticidal
      activity of 13 Myristica seed compounds against female B. germanica was examined
      by using the filter-paper contact toxicity and vapor phase toxicity bioassays.
      Results were compared with those of the other 23 known compounds of Myristica
      seed and currently used insecticides: dichlorvos, deltamethrin, permethrin, and
      propoxur. In contact toxicity tests using female B. germanica, (IS)-(-) -beta
      pinene (0.06 mg/cm2) was the most toxic insecticide, based on 24-h LD50 values.
      The insecticidal activity of this compound was comparable with that of permethrin
      (0.05 mg/cm2). (1R)-(+) -Camphor, (1S)-(-) -camphor, dipentene, (1R)-(+) -3
      pinene, and (+)-alpha-terpineol (0.10-0.14 mg/cm2) were more toxic than propoxur
      (0.19 mg/cm2). (E)-Sabinene hydrate and propoxur were almost equitoxic. Potent
      insecticidal activity also was observed with (R)-(+) -citronellal, (S)-(-) 
      citronellal, (R)-(-) -alpha-phellandrene, (1S)-(-) -alpha-pinene, (1R)-(+) -alpha
      pinene, and safrole (0.27-0.48 mg/cm2). In vapor phase toxicity tests, the
      compounds tested were effective in closed but not in open containers. These
      results indicate that the effect of these compounds was largely a result of
      action in the vapor phase. Myristica seed compounds described merit further study
      as potential insecticides or as leads for the control of cockroaches.

PMID- 17547242
TI  - Human plague in the southwestern United States, 1957-2004: spatial models of
      elevated risk of human exposure to Yersinia pestis.
AB  - Plague is a rare but highly virulent flea-borne zoonotic disease caused by the
      Gram-negative bacterium Yersinia pestis Yersin. Identifying areas at high risk of
      human exposure to the etiological agent of plague could provide a useful tool for
      targeting limited public health resources and reduce the likelihood of
      misdiagnosis by raising awareness of the disease. We created logistic regression
      models to identify landscape features associated with areas where humans have
      acquired plague from 1957 to 2004 in the four-corners region of the United States
      (Arizona, Colorado, New Mexico, and Utah), and we extrapolated those models
      within a geographical information system to predict where plague cases are likely
      to occur within the southwestern United States disease focus. The probability of
      an area being classified as high-risk plague habitat increased with elevation up
      to approximately 2300 m and declined as elevation increased thereafter, and
      declined with distance from key habitat types (e.g., southern Rocky Mountain
      pinon--juniper [Pinus edulis Engelm. and Juniperus spp.], Colorado plateau pinon-
      juniper woodland, Rocky Mountain ponderosa pine (Pinus ponderosa P.& C. Lawson
      var. scopulorum), and southern Rocky Mountain juniper woodland and savanna). The
      overall accuracy of the model was >82%. Our most conservative model predicted
      that 14.4% of the four-corners region represented a high risk of peridomestic
      exposure to Y. pestis.

PMID- 17547243
TI  - Intraspecific variation of second internal transcribed spacer of nuclear
      ribosomal DNA among populations of Anopheles (Kerteszia) cruzii (Diptera:
      Culicidae).
AB  - Anopheline species of the subgenus Kerteszia, including Anopheles (Kerteszia)
      cruzii Dyar & Knab (Diptera: Culicidae), are bromeliad-malaria vectors in the
      Atlantic rain forest of Brazil. Morphological, genetic, and molecular
      polymorphisms among different populations of An. cruzii have been reported, and
      it has been suggested that this taxon includes a complex of cryptic species.
      Specimens of An. cruzii were collected in the states of SHo Paulo and Santa
      Catarina, from locations where autochthonous malaria cases have been reported
      during the last decade. The second internal transcribed spacers (ITS2) of nuclear
      ribosomal DNA of the captured specimens were sequenced and compared with each
      other. Intraspecific ITS2 sequence polymorphisms were identified, and nucleotide
      divergence among specimens varied from 0.3 to 0.9%. The number of nucleotides in
      the ITS2 sequences of these mosquitoes varied from 327 to 334, and the CG
      contents varied from 61.7 to 62%. The data provide further indication of An.
      cruzii being a complex of cryptic species.

PMID- 17547244
TI  - "I came so that they may have life": amative space and faith as vital concern.
AB  - This article describes four attributes of faith as vital concern--relational
      spontaneity, responsiveness, receptiveness, and vulnerability--which are key
      ingredients to subjective and intersubjective experiences of being alive and
      real. The metaphor, amative space, refers to the processes and dynamics that make
      faith as vital concern a viable possibility between and among people. The author
      depicts these processes as four, interrelated dialectical pairs--recognition
      negation, surrender-generation, trust-distrust, and disruption-repair. The four
      attributes of faith as vital concern combined with the processes and dynamics of
      amative space can be used as a relational model to understand faith experience
      and interactions of individuals and groups.

PMID- 17547245
TI  - A preliminary proposal for a scale to measure the effectiveness of pastoral care
      with family members of hospitalized patients.
AB  - The authors conducted an electronic search of the Medline database for articles
      measuring family satisfaction. Content analysis was then performed on the
      relevant studies to determine the types of themes included in scales measuring
      family satisfaction in healthcare settings. The authors used these themes to
      develop a scale for measuring the effectiveness of pastoral care with family
      members. A convenience sample of chaplains that was asked to judge the usefulness
      of each of the scale items, rated them all, on average, to be "somewhat useful"
      to "very useful" for evaluating chaplains' effectiveness. The value of the scale
      is discussed in terms of its being a more outcome-oriented measure of
      effectiveness compared to typical family satisfaction instruments.

PMID- 17547246
TI  - Patterns of conversation between clergy and their parishioners and referral to
      other professionals.
AB  - Clergy deal with mental and physical health care issues as well as spiritual
      concerns within their congregations. Collaboration with psychotherapists and
      physicians could be argued to be "best practice" by clergy, but little is known
      about how clergy collaborate, particularly in non-hospital settings. This study
      describes reported practice patterns of referral by clergy in the context of
      their conversations with parishioners. Clergy report that parishioners regularly
      express psychosocial and medical concerns to them, and clergy also initiate these
      conversations. Clergy refer to medical providers and psychotherapist 23% of the
      time, and these referrals are found to be helpful, even though the professionals
      rarely connect with each other. Physicians and psychotherapists report they refer
      to clergy 10% and 24% of the time, respectively, and often find these referrals
      helpful. Further research is needed to understand the barriers and bridges to
      collaboration between professionals in different domains of care.

PMID- 17547247
TI  - The clergy: a valuable resource for church members with alcohol problems.
AB  - The role of the minister or pastor is pivotal in the development and operation of
      church-based services and programs and in the delivery of services. They can
      initiate changes and can equip the officers and members so that families troubled
      by substance abuse issues can find a climate of acceptance, understanding, and
      recovery in the local congregation. They can also serve as a referral source to
      members of the mental health professionals for assistance with alcohol and other
      substance abuse problems. For our purposes in this article, the term "clergy"
      refers to congregational and parish clergy. The focus of this discussion pertains
      to the role of clergy in providing assistance for members of their congregations
      with substance abuse problems. Implications and recommendations for
      collaborations and specific resources are also included that may increase the
      awareness of those issues and to increase effectiveness of service to those
      needing it.

PMID- 17547248
TI  - The psalms of lament and the transformation of sorrow.
AB  - This article explores how the psalms of lament can be used as a resource for
      pastoral care, and how ultimately they point toward the transformation of sorrow.
      Relying on Walter Brueggemann's scheme of orientation--disorientation--new
      orientation as a way to recognize the depth of human experience, the article sees
      the laments as honest engagement and dialogue with God within a covenantal
      relationship where hurt and pain are acknowledged rather than denied and avoided.
      The implications of using the psalms of lament in pastoral care and in Clinical
      Pastoral Education are discussed.

PMID- 17547249
TI  - Murder and faith: a reflected case study of pastoral interventions in traumatic
      grief.
AB  - Pastoral response to death in the family of a congregate is familiar terrain for
      most ministers. Pastors are often called upon to pray for the sick, comfort the
      bereaved, and preside at memorial services and graveside gatherings. While most
      get some orientation in the work of death and dying in seminary, few are prepared
      to minister effectively to church members who suffer traumatic bereavement caused
      by human-perpetrated violence. This paper describes the power of facilitated
      cathartic narrative, bearing witness, and reflective meaning-making in a case
      study involving a pastor, his wife, and the grief-stricken widow of a murdered
      comrade in ministry.

PMID- 17547250
TI  - Psychoanalysis, the brain, and amazing grace.
AB  - Believing that there are many paths to wholeness, the author attempts to
      investigate three seemingly diverse concepts of healing--spirituality,
      psychoanalysis, and brain biology. He demonstrates how these three modes may have
      more in common than often has been historically recognized and this leads him to
      celebrate that reality.

PMID- 17547251
TI  - Unconditional giving and unconditional taking: empathy and narcissism among
      pastors.
AB  - Empathy is a key factor in successful pastoral contact. This article reports on
      an investigation among pastors of the relationship between empathy and
      narcissism, a personality trait which has acquired considerable importance in
      recent years. The article distinguishes between several dimensions of empathy and
      narcissism. In the case of empathy these dimensions are perspective-taking,
      fantasy, empathic concern, and personal distress, and in the case of narcissism
      they are centripetal narcissism, centrifugal narcissism, isolation, and self
      satisfaction. The meaning of the relationship between empathy and narcissism for
      pastoral performance is discussed.

PMID- 17547252
TI  - Will we ring the bell? Clinical Pastoral Education (CPE) with the Salvation Army.
AB  - This article describes an "experimental" Clinical Pastoral Education (CPE)
      program, designed for eight Salvation Army Officers [Ministers] who were located
      in cities from Washington, DC to Antonio, Texas. The four Consecutive Units were
      accomplished over a two year span, with most of the work taking place by e-mail
      and long-distance telephone conference calls. One of the important questions to
      be answered is, "Can CPE be done mostly long-distance"?

PMID- 17547253
TI  - A lesson from Katrina: pastoral care from an Asian theological perspective.
AB  - Situating pastoral caregivers in the dramatic catastrophe caused by hurricane
      "Katrina" in New Orleans, this article attempts to address some appropriate
      pastoral responses toward the disaster from an Asian theological perspective. The
      article highlights the significance of remembrance and connection rather than
      repression and forgetfulness in order to bring justice to all victims of Katrina.
      It builds on Jacoby's "social amnesia," calls for redefining the meaning of
      community, and attempts to address the human predicaments on the surface of
      Katrina through an Asian perspective. In order to address pastoral responses, the
      article builds upon Martin Luther King, Jr.'s concept of interrelatedness and
      shared destiny. It critically examines Jung Young Lee's theology of marginality,
      and draws the pastoral implications of this theology of marginality with respect
      to Katrina.

PMID- 17547254
TI  - A Spiritual Issues Discussion Group for psychiatric in-patients.
AB  - This article describes a weekly Spiritual Issues Discussion Group, co-led by the
      author, open to psychiatric in-patients at New York Presbyterian Hospital. The
      group is open to people of all faiths and endeavors to allow participants to
      explore the many relationships between their beliefs, past experiences, mental
      illness, and spiritual lives. The article also summarizes the professional
      literature reporting on similar groups and suggests areas for further study.

PMID- 17547255
TI  - Pastor to immigrants.

PMID- 17547256
TI  - Was I really suffering?

PMID- 17547257
TI  - The Gadarene Demoniac finds wholeness.

PMID- 17547258
TI  - Dementia, my father's final gift!

PMID- 17547259
TI  - Everything I needed to know about chaplaincy I learned from Sukkot.

PMID- 17547260
TI  - The right time for me.

PMID- 17547261
TI  - Getting what we don't deserve.

PMID- 17547262
TI  - New evidence report on nurse staffing and quality of patient care.

PMID- 17547263
TI  - A basic guide to understanding plasma B-type natriuretic peptide in the diagnosis
      of congestive heart failure.
AB  - Congestive heart failure (CHF) affects millions of Americans and is responsible
      for the highest number of annual hospital admissions (Braunwald, 2005). Recent
      developments have occurred regarding clinical markers used in diagnosing CHF,
      including plasma B-type natriuretic peptide (BNP). In this article, the
      pathophysiology of plasma BNP in the CHF patient, indications for its use,
      benefits, and factors that can affect plasma BNP levels are explored.

PMID- 17547264
TI  - Older women's breast screening behaviors: what nurses need to know.
AB  - A study was conducted to assess whether the screening behaviors of breast self
      examination, mammography, and clinical breast examination differed among older
      women. Results have implications for nurses caring for older women.

PMID- 17547265
TI  - Nurse-physician collaboration: a comparison of the attitudes of nurses and
      physicians in the medical-surgical patient care setting.
AB  - Past literature reveals the multiple dimensions of the nurse-physician
      relationship. The current study was conducted within medical-surgical units of a
      major medical center in the South to determine attitudes of nurses and physicians
      regarding their collaboration.

PMID- 17547266
TI  - Pursuing safe medication use and the promise of technology.
AB  - Medical-surgical nurses are challenged to reduce and eliminate medication errors.
      They use technologic innovations aimed at error prevention, yet medication errors
      persist. The importance of improved decision making through computerized systems
      in the prevention of medication errors is emphasized.

PMID- 17547267
TI  - Care of the breastfeeding mother in medical-surgical areas.
AB  - Benefits and myths of breastfeeding may interfere with the breastfeeding
      relationship during maternal hospitalization. Guidelines for maintaining the
      breastfeeding relationship and/or protecting the milk supply during contact with
      the health care system outside of the maternal child area are presented.

PMID- 17547268
TI  - The effect of respiratory rate and ingestion of hot and cold beverages on the
      accuracy of oral temperatures measured by electronic thermometers.
AB  - Researchers examined hot and cold beverage consumption, tachypnea, and bradypnea
      effects on oral electronic thermometer readings. Results indicate that waiting at
      least 30 minutes after drinking yields a more accurate reading. Outcomes also
      suggest that bradypnea may create false temperature elevations.

PMID- 17547269
TI  - A competency-based approach to expanding the cancer care workforce.

PMID- 17547270
TI  - Critique of 'nurse-physician collaboration: a comparison of the attitudes of
      nurses and physicians in the medical-surgical patient care setting'.
AB  - This Research Roundtable has taken you through the research report from
      describing a problem and defending it as a significant or important problem, to
      stating the purpose of the study and formulating a research question, designing
      research to answer the research question and selecting methods appropriate to
      answer the research question (sampling methods, data collection methods, data
      analysis methods), and presenting and interpreting findings.

PMID- 17547271
TI  - Diabetes.

PMID- 17547272
TI  - A historical perspective on the nursing shortage.

PMID- 17547273
TI  - Moral courage: a virtue in need of development?

PMID- 17547274
TI  - [Sympathomimetics in ADHD. Cardiovascular risks, FDA warns].

PMID- 17547275
TI  - [Insufficient studies of diagnostic cancer tests. Neither systematic review nor
      original studies come up to expectations].

PMID- 17547276
TI  - [Eradication of polio is taking time].

PMID- 17547277
TI  - [Povidone hypersensitivity--extremely unusual or underestimated? The pharmaceutic
      aid povidone was earlier not considered toxic or allergenic].

PMID- 17547278
TI  - [Difficult to decide whether neck symptoms are work-related. New studies and
      identification of general risk factors form a better basis].

PMID- 17547279
TI  - [Nanomedicine challenges European ethicians, lawyers and toxicologists].

PMID- 17547280
TI  - [More about the significance of "social engineering" in psychiatry].

PMID- 17547281
TI  - [Beautiful new psychiatry--Stockholm's perspective...].

PMID- 17547282
TI  - [Can we afford not to cooperate?].

PMID- 17547283
TI  - [We want the most suitable persons as leaders at SAS].

PMID- 17547284
TI  - [New guidelines support physician-assisted suicide!].

PMID- 17547285
TI  - [Create a "tattooe-free" stick channel].

PMID- 17547286
TI  - [Research ethics--reflections on research committee work].

PMID- 17547287
TI  - New treatment options in systemic diseases.

PMID- 17547288
TI  - Advances in genetic diseases of the kidney: impact on renal medicine.

PMID- 17547289
TI  - Pulmonary-renal syndromes.
AB  - Pulmonary-renal syndromes or lung-kidney syndromes are clinical syndromes defined
      by a combination of diffuse alveolar haemorrhage (DAH) and glomerulonephritis.
      Pulmonary-renal syndromes are not a single entity, but are caused by a wide
      variety of diseases, including various forms of primary systemic vasculitis
      (especially Wegener's granulomatosis and microscopic polyangiitis), Goodpasture's
      syndrome (associated with autoantibodies to the alveolar and glomerular basement
      membrane) and systemic lupus erythematosus. The diagnosis rests on the
      identification of particular patterns of clinical, radiologic, pathologic and
      laboratory features. Serologic testing is important in the diagnostic work-up of
      patients presenting with a pulmonary-renal syndrome. The majority of cases of
      pulmonary-renal syndrome are associated with ANCAs, either c-ANCA or p-ANCA, due
      to autoantibodies against the target antigens proteinase-3 and myeloperoxidase
      respectively. The antigen target in Goodpasture's syndrome is type IV collagen,
      the major component of basement membranes. Diffuse alveolar haemorrhage is
      characterized by the presence of a haemorrhagic bronchoalveolar lavage (BAL) in
      serial BAL samples. In the clinical setting of an acute nephritis syndrome,
      percutaneous renal biopsy is commonly performed for histopathology and
      immunofluorescence studies. Treatment of generalized ANCA-associated vasculitis
      consists of corticosteroids and immunosuppressive agents such as cyclophosphamide
      (as induction therapy) or azathioprine (as maintenance therapy once remission has
      been achieved). The combination of plasmapheresis with these cytotoxic agents and
      steroids is effective in patients with Goodpasture's syndrome, especially if
      instituted early in the course of the disease. Recent evidence suggests that
      patients with severe ANCA-associated vasculitis, defined by the presence of
      diffuse alveolar haemorrhage and/or severe renal involvement (creatinine
      concentration > 5.7 mg/dl), might benefit from plasma exchange in combination
      with cyclophosphamide and corticosteroids.

PMID- 17547290
TI  - Diabetes and the endothelium.
AB  - Abnormal endothelial function plays a pivota role in the pathogenesis of diabetic
      complications. Due to lack of autoregulation of glucose transport in the presence
      of high extracellular glucose concentrations, intracellular hyperglycaemia
      induces a series of metabolic changes that ultimately lead to the genesis of both
      microvascular complications (the hallmark of chronic hyperglycaemic states) and
      macrovascular damage. In type 2 diabetes, the abnormalities associated with
      insulin resistance and the metabolic syndrome phenotype (such as high blood
      pressure, dyslipidaemia, abnormal levels of circulating adipokines and free fatty
      acids e.g.) also contribute to accelerate the endothelial damage sustained as a
      result of chronic exposure to hyperglycaemia. Only recently was a unifying theory
      proposed to account for the four major abnormal pathways activated by chronic
      hyperglycaemia and thought to damage the endothelial cell and to trigger the
      downstream micro- and macrovascular complications associated with diabetes
      mellitus. This pathophysiological sequence revolves around the metabolic
      abnormalities triggered as a result of overproduction of superoxide by the
      mitochondrial electron transport chain and subsequent inhibition of the key
      glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase by increased activity
      of nuclear poly(ADP-ribose)polymerase.

PMID- 17547291
TI  - Dopps estimate of patient life years attributable to modifiable haemodialysis
      practices in Belgium.
AB  - BACKGROUND: Various organizations have published clinical practice guidelines for
      the care of haemodialysis patients. However, it is unknown to what extent
      improving or even reaching perfect compliance with guidelines would improve the
      survival of HD patients in Belgium. METHODS: Using data from the second phase of
      the Dialysis Outcomes and Practice Patterns Study (DOPPS), the proportion of
      haemodialysis patients failing to meet six key practice targets (Kt/V > or = 1.2,
      haemoglobin > or =11 g/dl, phosphate 1.1-1.5 mmol/l, calcium 2.1-2, 4 mmol/l,
      albumin > or =40 g/l, and facility catheter use < or =10%) was calculated along
      with the relative risk of mortality associated with being outside these targets.
      The life years potentially gained from adherence to the six targets, both
      separately and all six together were then estimated. RESULTS: The percentage of
      patients outside the targets were as follows: 30.3%, Kt/V; 33.6%, haemoglobin;
      56.2%, phosphate; 58.2%, calcium; 67.1%, albumin; and 91.1%, catheter. Estimated
      patient life years gained with improved compliance with guidelines was highest
      for albumin (3.670) and catheter use (2.331) but still substantial for the other
      four targets (ranging from 551 to 1.258). The total of patient years gained if
      100% of patients have all six practices brought within target reaches 7.516
      years. A conservative estimate of 50% of patients within all targets still yields
      an improvement of survival of 3.958 patient years. CONCLUSION: This analysis
      suggests large opportunities to improve HD patient care in Belgium. The avoidance
      of HD catheters, with the use of AV fistulas whenever possible, should be given a
      high priority. Admittedly, these calculations assume causality or partial
      causality that has not been definitively proven. Still, if causality is only
      partial, the results emphasize that the improvement of patient care through
      adherence to targets of clinical guidelines might be substantial and all Belgian
      nephrologists and staff members of dialysis units should carefully pursue every
      potential effort.

PMID- 17547292
TI  - Hepatitis C and insulin resistance: mutual interactions. A review.
AB  - Worldwide approximately 200 million people are chronically infected with
      hepatitis C virus (HCV). Chronic HCV infection represents the leading cause of
      liver cirrhosis and the main indication for liver transplantation in the western
      world. In addition, chronic HCV infection is associated with numerous clinical
      manifestations, including type 2 diabetes. An obvious and frequently suggested
      explanation for the connection between HCV infection and type 2 diabetes is that
      cirrhosis by itself causes insulin resistance. However, the prevalence of type 2
      diabetes in HCV cirrhosis is higher than in HBV cirrhosis (23.6% vs 9.4%). This
      suggests that HCV infection by itself can lead to insulin resistance and
      predispose to the onset of type 2 diabetes. First, HCV core protein induces
      hepatic steatosis by inhibition of microsomal triglyceride transfer protein and
      hepatic steatosis causes insulin resistance. Secondly, HCV core protein inhibits,
      through elevation of TNF-alfa and other factors, the insulin-signalling pathways
      causing insulin resistance. Moreover, recent data strongly suggest that insulin
      resistance is an important predictor of poor response to antiviral therapy in
      chronic hepatitis patients treated with peginterferon plus ribavirin.

PMID- 17547293
TI  - Heterotopic gastric mucosa in gallbladder associated with kidney agenesis and
      congenital hip dysplasia.
AB  - Heterotopic gastric tissue in the gallbladder is an extremely rare condition.
      There is not any specific clinical or laboratory finding and correct diagnosis is
      not possible before histopathological examination. Preoperative diagnosis usually
      resembles a polypoid Lesion or a fixed gallstone. We reported a 34-year-old
      female patient with heterotopic gastric mucosa in the gallbladder associated with
      congenital hip dysplasia and kidney agenesis. Laparoscopic cholecystectomy was
      performed and histopathology of the resected specimen showed that the "polyp"
      consisted of heterotopic gastric mucosa with glands of body and fundic type. Some
      cases of heterotopia in the gallbladder come from metaplasia, and may be one of
      the causes of gall bladder cancer. We discussed the clinical and histologic
      features of heterotopic gastric tissues and reviewed reported cases in the
      literature.

PMID- 17547294
TI  - Severe hiccups and intravenous lidocaine.
AB  - We report the case of a patient in whom the use of intravenous Lidocaine to treat
      incapacitating hiccups was a success. Intravenous lidocaine should be considered
      as an alternative treatment for severe hiccups when classical medications are
      ineffective or produce side effects.

PMID- 17547295
TI  - Immune reconstitution inflammatory syndrome in an HIV/TB co-infected patient four
      years after starting antiretroviral therapy.
AB  - The Immune reconstitution inflammatory syndrome (IRIS) after starting
      antiretroviral therapy for HIV is well known. We describe an HIV seropositive
      woman, presenting 2 IRIS episodes associated with Mycobacterium tuberculosis.
      Exceptional was that the last episode occurred 4 years after initiating
      antiretroviral treatment, when her CD4+ lymphocyte count had been around 300
      cells/mm3 for one year.

PMID- 17547296
TI  - Infection of the thyroid gland caused by Campylobacter fetus subsp. fetus.
AB  - We report what we consider to be the first case of an abscess of the thyroid
      gland due to Campylobacter fetus subsp. fetus (C. fetus) in a patient suffering
      from hyperthyroidism. C. fetus is known as a rare and opportunistic pathogen in
      humans, causing a broad variety of systemic infections. Acquisition by humans is
      thought to occur through contact with animals or animal products and to start as
      a gastro-intestinal colonization. The detection of C. fetus in stool is
      challenging, since culture efforts are generally directed in order to fulfil
      growth requirements of C.jejuni, a much more common enteric pathogen. Detection
      of C. fetus in non-stool samples is even more challenging since routine culture
      doesn't imply prolonged incubation (>72h), selective media and microaerophilic
      conditions. It is therefore not unlikely that human infections caused by C. fetus
      occur more often than generally assumed.

PMID- 17547297
TI  - A case for operational approach in advanced research projects-the augmented
      cognition story.

PMID- 17547298
TI  - Military medical research on cognitive performance: the warfighter's competitive
      edge.

PMID- 17547299
TI  - 21st century human-system computing: augmented cognition for improved human
      performance.

PMID- 17547300
TI  - Mitigation of three types of stress on cognitive performance.
AB  - The development of reliable and valid generalizations about realworld behavior,
      based on laboratory and simulation experiments, continues to be a major challenge
      in the applied behavioral sciences, particularly cognitive psychology. This
      challenge, and the tradeoff between reliability and generalizability, is
      discussed in light of the principal goal of applied science, which is successful
      generalization, in contrast to basic science, which is the generation of
      successful theory. Cognitive psychology has been successful in providing useful
      guidance for the design of performance enhancing techniques to mitigate the
      effects of stress that can be found in military operations and other applied
      settings. The manuscripts in this section on Cognitive Foundations of Human
      Information Processing address three types of stress occurring in the operational
      environment-sleep deprivation, cognitive load, and physical exertion-and options
      that may aid in monitoring or counteracting their negative effects. Separately,
      the manuscripts focus on: the impairing effects of total sleep deprivation on
      attention versus cognitively demanding tasks, as well as language-based tasks and
      the utility of short probe tasks to monitor these effects; cognitive load during
      driving and the ability of supplemental cues to improve performance and
      subjective questionnaires to assess load status; and the degrading effects of
      physical exertion on vigilance aspects of cognitive performance and its
      implications in the military environment. In concluding remarks, based on
      Tinbergen's four fundamental interrogatives, the need is underscored for the
      field of cognitive psychology to go beyond descriptive findings of human behavior
      into the realm of scientific explanatory answers.

PMID- 17547301
TI  - Human performance under sustained operations and acute sleep deprivation
      conditions: toward a model of controlled attention.
AB  - INTRODUCTION: Although a number of studies have examined the effects of sleep
      deprivation on performance, the results are not easily explained. The purpose of
      the current study was to examine the effects of sustained operations and acute
      sleep deprivation on tasks that require a wide range of information processing.
      The current study also provided preliminary data on the use of the controlled
      attention model to better understand the effects of sleep deprivation. METHODS:
      There were 24 college students who were paid to remain awake for one night and
      complete a variety of cognitive and vigilance tasks. Each task was administered
      four times during the night, once in each testing session (17:30-21:30, 21:45
      01:45, 02:30-06:30, and 06:45-10:45). All tasks were counterbalanced across the
      testing sessions. RESULTS: The data were converted to z-scores and repeated
      measures ANOVAs were completed. Performance did not significantly decrease on the
      more complex cognitive tasks over the night of sleep deprivation. Performance on
      the vigilance tasks decreased significantly across the night. CONCLUSIONS:
      Examining the characteristics of the cognitive tasks indicated that although they
      required different types of processing, they encouraged the participants to
      remain attentive to and engaged in the task. In contrast, the vigilance tasks
      were less intrinsically interesting and engaging. Thus, it seems likely that the
      participants were less capable of maintaining attention on the vigilance tasks
      than the cognitive tasks. These results indicate that a controlled attention
      model may be useful in better understanding the effects of sustained operations
      and sleep deprivation on performance.

PMID- 17547302
TI  - Language performance under sustained work and sleep deprivation conditions.
AB  - INTRODUCTION: Although substantial research has been completed on the effects of
      sleep deprivation on performance, very little research has focused on language
      based tasks. The purpose of the current study was two-fold: 1) to determine the
      extent to which short-term sleep deprivation affects language performance; and 2)
      to examine whether relatively short and easy-to-administer "probe" tasks could
      signal decrements in language performance under sleep deprivation conditions.
      METHODS: There were 38 non-native English-speaking students who were paid to
      complete a 28-h sleep deprivation study. The participants completed several
      potential cognitive and vigilance probe tasks and a variety of language-based
      tasks. Each task was administered four times, once in each testing session during
      the night (18:30-22:30, 23:00-03:00, 03: 30-07:30, and 08:00-12:00). All tasks
      were counterbalanced across the testing sessions. RESULTS: Repeated-measures
      ANOVAs indicated that language tasks that required sustained attention and higher
      level processing (e.g., reading comprehension) were negatively affected by sleep
      deprivation, whereas other tasks that relied primarily on more basic language
      processing (e.g., antonym identification) were not affected. Hierarchical linear
      modeling analyses assessed how well the probe tasks predicted language
      performance. These results indicated that performance accuracy and/or speed on
      many of the probe tasks predicted decrements in language performance.
      CONCLUSIONS: These findings suggest that sustained work conditions and sleep
      deprivation negatively affect some types of language performance. Moreover, the
      use of probe tasks indicates that easy-to-administer tasks may be useful to
      identify when detriments are likely to occur in language-based performance under
      sleep deprivation conditions.

PMID- 17547303
TI  - Sensitivity of subjective questionnaires to cognitive loading while driving with
      navigation aids: a pilot study.
AB  - INTRODUCTION: Developers of future forces are implementing automated aiding for
      driving tasks. In designing such systems, the effect of cognitive task
      interference on driving performance is important. The crew of such vehicles may
      have to occasionally perform communication and planning tasks while driving.
      Subjective questionnaires may aid researchers to parse out the sources of task
      interference in crew station designs. METHOD: In this preliminary study, sixteen
      participants drove a vehicle simulator with automated road-turn cues (i.e.,
      visual, audio, combined, or neither) along a course marked on a map display while
      replying to spoken test questions (i.e., repeating sentences, math and logical
      puzzles, route planning, or none) and reporting other vehicles in the scenario.
      Following each trial, a battery of subjective questionnaires was administered to
      determine the perceived effects of the loading on their cognitive functionality.
      RESULTS: Considering the performance, the participants drove significantly faster
      with the road-turn cues than with just the map. They recalled fewer vehicle
      sightings with the cognitive tests than without them. Questionnaire results
      showed that their reasoning was more straightforward, the quantity of information
      for understanding higher, and the trust greater with the combined cues than the
      map-only. They reported higher perceived workload with the cognitive tests. The
      capacity for maintaining situational awareness was reduced with the cognitive
      tests because of the increased division of attention and the increase in the
      instability, variability, and complexity of the demands. The association and
      intuitiveness of cognitive processing were lowest and the subjective stress
      highest for the route planning test. Finally, the confusability in reasoning was
      greater for the auditory cue with the route planning than the auditory cue
      without the cognitive tests. CONCLUSION: The subjective questionnaires are
      sensitive to the effects of the cognitive loading and, therefore, may be useful
      for guiding the development of automated aid designs.

PMID- 17547304
TI  - The effects of movement and physical exertion on soldier vigilance.
AB  - INTRODUCTION: The effects of movement and physical exertion on cognitive
      processes remain unclear. Some studies report improvements in information
      processing while others report decrements or no change. To address relationships
      between movement, physical exertion, and cognitive performance, vigilance
      performance while soldiers walked with a heavy (40 kg) load was examined.
      METHODS: Volunteers (n = 18) completed six 30-min test sessions on separate days:
      standing; walking with or without obstacles; while carrying a 40-kg load or no
      load. Suprathreshold visual, auditory or tactile stimuli were presented during
      the vigilance task. Dependent measures included accuracy, response time and
      distance traversed. RESULTS: Volunteers reported higher perceived exertion (p <
      0.05) when carrying a load and these ratings increased with time (p < 0.05).
      There were fewer correct responses on the vigilance task when carrying a load (p
      < 0.05) or when walking over obstacles (p < 0.05). Vigilance performance was
      superior with auditory compared with visual or tactile stimuli (p < 0.05). Less
      distance was covered when carrying a load (p < 0.05), traversing the course with
      obstacles (p < 0.05), and when responding to a tactile, compared with an
      auditory, stimulus (p < 0.05). DISCUSSION: These results indicate walking around
      obstacles and the exertion of load carriage affect performance on the basic
      cognitive function of vigilance. Furthermore, they raise fundamental questions
      about whether cognitive performance data collected from sedentary, rested
      volunteers are applicable to individuals, including dismounted soldiers, engaged
      in tasks that concurrently require physical and cognitive resources.

PMID- 17547305
TI  - Implications for studying team cognition and team performance in network-centric
      warfare paradigms.
AB  - Network-centric warfare's (NCW) information-rich systems involving sophisticated
      sensors, tracking systems, smart weapons, and enhanced digital communications
      threaten to overload combatants with voluminous amounts of data. It is unclear
      whether warfighters will perceive such extensive data as actionable information
      to which they will respond accurately in a timely enough manner. Members of small
      teams in command and control centers, operating in crew-served vehicles, or
      simply "grunting it out" as ground-pounding infantrymen, may be disparately
      separated by space, but will communicate and be connected by electronic linkages,
      e.g., radio, text messages, situation displays, or global positioning data.
      However, team members will also have to remember shared mental models of tasks at
      hand, pay attention to and share common situation awareness in complex
      operational environments, perform team cognition and team coordination, and
      integrate both lower and higher cognitive processes with those of team behaviors.
      Such exceptional capabilities are required more now than ever before; such
      capabilities today are far from assured. After two workshops to establish
      performance metrics for assessing cognitive performance of military personnel in
      NCW, this preface introduces five manuscripts addressing team cognition and team
      performance from both a theoretical and a practical perspective. The authors of
      this preface question if NCW, and perhaps the politico-social ramifications of
      modern warfare, have already outstripped behavioral scientists' approach to
      researching team cognition and team performance-expertise that is so crucially
      needed for combatants on the rapidly changing 21st-century battlegrounds.

PMID- 17547306
TI  - Augmenting team cognition in human-automation teams performing in complex
      operational environments.
AB  - There is a growing reliance on automation (e.g., intelligent agents, semi
      autonomous robotic systems) to effectively execute increasingly cognitively
      complex tasks. Successful team performance for such tasks has become even more
      dependent on team cognition, addressing both human-human and human-automation
      teams. Team cognition can be viewed as the binding mechanism that produces
      coordinated behavior within experienced teams, emerging from the interplay
      between each team member's individual cognition and team process behaviors (e.g.,
      coordination, communication). In order to better understand team cognition in
      human-automation teams, team performance models need to address issues
      surrounding the effect of human-agent and human-robot interaction on critical
      team processes such as coordination and communication. Toward this end, we
      present a preliminary theoretical framework illustrating how the design and
      implementation of automation technology may influence team cognition and team
      coordination in complex operational environments. Integrating constructs from
      organizational and cognitive science, our proposed framework outlines how
      information exchange and updating between humans and automation technology may
      affect lower-level (e.g., working memory) and higher-level (e.g., sense making)
      cognitive processes as well as teams' higher-order "metacognitive" processes
      (e.g., performance monitoring). Issues surrounding human-automation interaction
      are discussed and implications are presented within the context of designing
      automation technology to improve task performance in human-automation teams.

PMID- 17547307
TI  - Characterizing team performance in network-centric operations: philosophical and
      methodological issues.
AB  - The recently promulgated doctrine of network-centric warfare suggests that
      increases in shared situation awareness and self-synchronization will be emergent
      properties of densely connected military networks. What it fails to say is how
      these enhancements are to be measured. The present article frames the discussion
      as a question of how to characterize team performance, and considers such
      performance in the context of its hypothetical components: situation awareness,
      workload, and error. This examination concludes that reliable measures of these
      constructs are lacking for teams, even when they exist for individual operators,
      and that this is due to philosophical and/or methodological flaws in their
      conceptual development. Additional research is recommended to overcome these
      deficiencies, as well as consideration of novel multidisciplinary approaches that
      draw on methodologies employed in the social, physical, and biological sciences.

PMID- 17547308
TI  - Markers for enhancing team cognition in complex environments: the power of team
      performance diagnosis.
AB  - Team cognition has been identified as a key component to achieve mission goals in
      dynamic, team-based, stressful, distributed and multicultural operations.
      Effective team performance in complex environments requires that team members
      hold a shared understanding of the task, their equipment, and their teammates.
      So, many of the simulation-based training (SBT) systems and programs have been
      designed (partly) to enhance shared/team cognition. However, these simulation
      systems lack the sufficient robustness in their performance assessment tools or
      capabilities (if they have any) to allow for a rich and deep understanding of
      team cognition. Therefore, the purpose of this article is fourfold: I) to present
      a brief account of team cognition; 2) to develop the concept of performance
      diagnosis and present SBT as an approach to the performance diagnosis of team
      cognition; 3) to present a set of illustrative behavioral markers of team
      cognition; and 4) to explicate how these elements (performance diagnosis, team
      cognition, and SBT) can be leveraged to increase training effectiveness through
      the development of performance profiles--a rich, detailed, and informative set of
      metrics--and cognitive and behavioral indicators or illustrative markers of team
      cognition. Research needs are discussed in terms of realizing the potential of
      this approach in operational and embedded training contexts.

PMID- 17547309
TI  - Linguistic correlates of team performance: toward a tool for monitoring team
      functioning during space missions.
AB  - INTRODUCTION: Approaches to mitigating the likelihood of psychosocial problems
      during space missions emphasize preflight measures such as team training and team
      composition. Additionally, it may be necessary to monitor team interactions
      during missions for signs of interpersonal stress. The present research was
      conducted to identify features in team members' communications indicative of team
      functioning. METHODS: Team interactions were studied in the context of six
      computer-simulated search and rescue missions. There were 12 teams of 4 U.S. men
      who participated; however, the present analyses contrast the top two teams with
      the two least successful teams. Communications between team members were analyzed
      using linguistic analysis software and a coding scheme developed to characterize
      task-related and social dimensions of team interactions. Coding reliability was
      established by having two raters independently code three transcripts. Between
      rater agreement ranged from 78.1 to 97.9%. RESULTS: Team performance was
      significantly associated with team members' task-related communications,
      specifically with the extent to which task-critical information was shared.
      Successful and unsuccessful teams also showed different interactive patterns, in
      particular concerning the frequencies of elaborations and no-responses. Moreover,
      task success was negatively correlated with variability in team members' word
      count, and positively correlated with the number of positive emotion words and
      the frequency of assenting relative to dissenting responses. CONCLUSIONS:
      Analyses isolated certain task-related and social features of team communication
      related to team functioning. Team success was associated with the extent to which
      team members shared task-critical information, equally participated and built on
      each other's contributions, showed agreement, and positive affect.

PMID- 17547310
TI  - Ready or not: enhancing operational effectiveness through use of readiness
      measures.
AB  - Current and future military operations require personnel to perform a multitude
      of mission tasks. Military personnel are required to execute these tasks, and to
      perform to high levels of expectation. Many of these tasks are complex and demand
      substantial cognitive readiness, which may optimize and enhance cognitive
      performance. Technologies are being developed to aid individual soldiers to
      successfully complete their missions; however, the proliferation of new
      technologies, coupled with the varying operational missions, make leveraging
      cognitive readiness a mandate for the achievement of military effectiveness and
      enhanced overall performance. It is important to have a militarily relevant
      psychological battery that can be used to assess each individual's cognitive
      capabilities and appraisals, factors that enhance military operational
      effectiveness. Assessing individual cognitive readiness becomes particularly
      important when researchers broaden their examinations of military effectiveness
      to assess team cognition, team behavior, and team effectiveness. We discuss the
      theoretical development and the components of the U.S. Army Research Laboratory's
      Readiness Assessment and Monitoring System (RAMS). Data from several studies are
      presented to illustrate the behavioral profiles of individuals in extreme
      operational environments. Data show how specific factors (e.g., personality,
      coping) contribute to performance in operational settings (e.g., command and
      control, chemical decontamination operations). Understanding the effect of
      cognitive readiness on overall military effectiveness not only has implications
      for selection, training, and system design, but also provides the basis for the
      proactive development and sustainment of optimal performance, both in individual
      soldiers, and in small teams or military

PMID- 17547311
TI  - Considerations of pharmacology on fitness for duty in the operational
      environment.
AB  - Coordination of strategies for transitioning psychoactive pharmacological
      compounds from basic laboratory research to the field environment has been an
      ongoing effort among military laboratories. Several workshops have been held
      specifically to address the operationally relevant issues and other military and
      scientific challenges as they relate to the enhancement and sustainability of
      cognitive performance. In this preface, we tie together recommendations of the
      Pharmacological Strategies Focus Team for one such Workshop, review current
      literature, and discuss findings reported at recent professional meetings. The
      papers presented within this pharmacology section are discussed. These section
      papers are organized into three areas of operational relevance--the first
      assesses the effectiveness of a treatment given for migraines, a condition with
      known detrimental effects on productivity and readiness; the second discusses
      ethical considerations surrounding the use of pharmaceutical countermeasures for
      fatigue in the operational environment; and the third discusses a case report
      highlighting the aeromedical considerations regarding selective serotonin
      reuptake inhibitors (SSRIs) and aviator flight performance, particularly as
      assessed with neuropsychological testing. The papers and commentaries in this
      section encourage us to consider the complex variables effecting the decisions to
      administer pharmacological agents, as the impact of their use is weighed against
      the cognitive performance effects they may have in the operational environment.

PMID- 17547312
TI  - Botulinum toxin type-a in the prevention of migraine: a double-blind controlled
      trial.
AB  - INTRODUCTION: Migraine is a frequent medical complaint. In military populations,
      migraine can be detrimental to productivity and troop readiness, and can be
      disqualifying for service in some military duty specialties. This study assessed
      the effectiveness of botulinum neurotoxin type-A (BTX-A) in reducing the
      frequency of migraines in known migraineurs. METHODS: There were 32 subjects
      (control = 17, test n = 15) who completed the assessment battery at baseline and
      monthly for 3 mo. Adult subjects with migraine headaches occurring more than 5
      times/month were recruited and randomized to receive placebo saline injection vs.
      BTX-A. The primary efficacy parameter was the average frequency of headache days
      for 3 mo. Secondary outcome measures were severity of attacks and quality of
      life. RESULTS: Quadratic trends were noted for headache severity (F (2,29) =
      14.1, p = 0.001) and headache indexes (F (2,29) = 4.5, p = 0.042) for both
      groups, suggesting changes in severity of head pain and overall intensity of
      headaches experienced over time; however, results were not significant for
      headache frequency and severity between groups. Paired t-tests of the headache
      index scores for the control group revealed a significant increase from the first
      to the third follow-up periods (t = -2.58, p = 0.020). Such a trend was not
      observed for the BTX-A group. Both groups, however, reported similarly low to
      moderate quality of life as a result of their migraines. CONCLUSIONS: This
      controlled trial failed to demonstrate efficacy of BTX-A in reducing the
      frequency of migraine headaches. The pattern headache index in the botox group,
      however, suggested a protective effect for botox against the headache severity.

PMID- 17547313
TI  - Recommendations for the ethical use of pharmacologic fatigue countermeasures in
      the U.S. military.
AB  - Culture and public opinion strongly influence debates on ethics-and what may be
      ethically acceptable to one nationality may be unacceptable to others. In
      military operations, some cognitive performance enhancement technologies are more
      ethically controversial than others. Of the enhancement technologies, use of
      psychoactive pharmaceuticals to alter behavior in healthy humans possibly
      presents the most controversial ethical challenge. Discussion of the bioethics of
      psychoactive enhancement agents is advisable because their military use is
      increasing while doctrine for their use remains limited. This paper focuses on
      psychoactive pharmaceuticals to enhance cognitive performance of military
      members. The topics addressed include: the use of psychoactive pharmaceuticals
      within a coalition framework; if ethical circumstances do exist for their use,
      what are these circumstances in clear and operationally useful terms; and
      guidelines to aid leaders in making ethically acceptable decisions. These
      questions should be answered: 1) Is use truly informed and voluntary--e.g., is an
      individual soldier requesting the medication with full understanding of its
      primary effects and side effects; 2) Is the medication safe for use in this
      individual, and safe within the context of the operational environment?; 3) Is
      the use of the medication consistent with its dosage and pharmacological function
      -i.e., is a sleep-inducing medication being used at appropriate doses, for a
      specified period, to facilitate sleep; and 4) Have available non-pharmacologic
      alternatives been fully utilized? This paper addresses a very narrow segment of
      the larger bioethics discussion: the use of pharmacologic enhancing agents in
      military members in times of war or national emergency.

PMID- 17547314
TI  - Premenstrual dysphoric disorder: treatment with sertraline, neuropsychological
      effects, and flight status.
AB  - INTRODUCTION: This case report reviews the aeromedical factors associated with
      considering a return to flight status of an aviator treated with sertraline 25 mg
      PO QD 5-7 d x mo(-1) for premenstrual dysphoric disorder (PMDD). Particular
      emphasis is given to her performance on serial neuropsychological assessments
      while both on and off of the medication. CASE PRESENTATION: Each testing occasion
      included a comprehensive battery of neuropsychological functioning, coupled with
      a blinded flight evaluation by a standardization pilot. The first testing
      occasion was on day 6 of menses while the aviator was taking 25 mg sertraline PO
      QD. The second testing occasion was completed 1 mo later, on day 6 of menses,
      while off the sertraline. The aviator's performance was compared with normative
      data at each testing occasion, as well as for possible significant change between
      testing occasions. DISCUSSION: An interpretation of this aviator's overall
      neuropsychological performance is discussed, with particular attention given to
      the potential cognitive effects of sertraline. In light of previously published
      aeromedical considerations related to selective serotonin reuptake inhibitor use
      by aviators, the aeromedical considerations regarding this aviator's use of
      sertraline for PMDD are also highlighted.

PMID- 17547315
TI  - Neurocognitive monitors: toward the prevention of cognitive performance
      decrements and catastrophic failures in the operational environment.
AB  - Network-centric doctrine and the proposed C41SR (command, control,
      communications, computers, intelligence, surveillance and reconnaissance)
      distributions to the individual warfighter require that the cognitive
      performance, judgment, and decision making of warfighters must be sustained and
      effectively managed in the forward operating environment, where various
      physiological and psychological stressors abound, in order to reduce human errors
      and catastrophic failures. The U.S. Army Medical Research and Materiel Command
      (USAMRMC) established the Cognitive Performance, Judgment, and Decision-Making
      Research Program (CPJDRP) in 2004 to direct research to this issue. A
      Neurophysiological Measures and Cognition Focus Team (NMFCT) was formed to work
      with augmented cognition investigators and to specifically address the
      development of neurophysiological measures as potential monitors of alertness
      cognitive state in warfighters. The USAM-RMC approach complemented the Defense
      Advanced Research Projects Agency (DARPA) Augmented Cognition approach, which
      focused on the detection of workload-related impaired cognitive state, and
      subsequent modification of information flow through automation. In this preface,
      the premise for neurophysiological measures as neurocognitive monitors is
      explained using an example of a neurophysiological index: the oculomotor measure,
      saccadic velocity. The progress of the NMFCT on the development of a
      neurocognitive monitor is described, as well as the recommendations of a 2005
      USAMRMC/Telemedicine and Advanced Technology Research Center (TATRC)-sponsored
      workshop. Awareness of neurocognitive monitoring is discussed, as are future
      endeavors related to operational testing and fieldability. Four papers are
      summarized in this Neurophysiological Monitoring and Augmented Cognition section
      involving technologies to enhance cognitive performance in the operational
      environment: one on dynamic cortical electroencephalography, two on oculometrics,
      and one on a spatial orientation enhancement system.

PMID- 17547316
TI  - Event-related cortical dynamics of soldiers during shooting as a function of
      varied task demand.
AB  - INTRODUCTION: Cortical dynamics of soldiers were examined during a reactive
      shooting task under varied task demands to investigate the effects of cognitive
      load on functional states of soldiers in real-time. METHODS: Task demand factors
      consisted of task load (single, dual), decision load (no-decision, choice
      decision), and target-exposure time (short, long). The Dismounted Infantryman
      Survivability and Lethality Testbed (DISALT) shooting simulator was programmed to
      generate the eight shooting scenarios and record weapon aim-point data while EEG
      was acquired continuously during each scenario. Event-related spectral
      perturbation (ERSP) was derived from single-trial data time-locked to the onsets
      of targets and peak amplitude and latency measures were analyzed in theta (4-7
      Hz) and upper alpha (11-13 Hz) frequency bands. RESULTS: The results are as
      follows: 1) a stimulus-evoked ERSP theta peak exhibited higher amplitude in the
      parietal region for choice- vs. no-decision scenarios and longer latency in the
      right central and temporal regions for dual- vs. single-task scenarios; and 2)
      ERSP alpha exhibited a progressive increase following the onset of targets with
      less of an increase in the left central region for dual- vs. single-task
      scenarios. DISCUSSION: ERSP theta synchronization reflects stimulus encoding and
      exhibits increased peak power with more complex decision demands and longer
      latency with secondary task demands, whereas ERSP alpha synchronization reflects
      motor preparation and exhibits less of an increase with secondary task demands
      during reactive target shooting tasks. This research contributes the first study
      of cortical dynamics of soldiers performing a reactive shooting task and has
      implications for theories of attention and cognitive workload, human factors
      engineering, and soldier performance.

PMID- 17547317
TI  - Identifying cognitive state from eye metrics.
AB  - INTRODUCTION: This paper describes a new approach for identifying cognitive state
      by using information obtained only from the eye. Data are collected from cameras
      mounted on a lightweight headband. A set of eye metrics captures essential eye
      information from the raw data of pupil size and point-of-gaze. The metrics are
      easily calculated every second, so that the entire set of metrics can be computed
      in real time. METHODS: Three studies provide empirical evidence to test whether
      the eye metrics are sufficient to discriminate between two different cognitive
      states. The first study examines the states of relaxed and engaged in the context
      of problem solving. The second study looks at the states of focused and
      distracted attention in the context of driving. The third study inspects the
      states of alert and fatigued in the context of visual search. Two statistical
      models are used to classify cognitive state for all three studies: linear
      discriminant function analysis and non-linear neural network analysis. Data for
      the models are eye metrics computed at 1-, 4-, and 10-s intervals. RESULTS: All
      discriminant function analyses are statistically significant, and classification
      rates are high. Neural network models have equal or better performance than
      discriminant function models across all three studies. DISCUSSION: The seven eye
      metrics successfully discriminate between the states in all studies. Models from
      individual participants as well as the aggregate model over all participants are
      successful in identifying cognitive states based on task condition.
      Classification rates compare favorably with similar studies.

PMID- 17547318
TI  - Task performance and eye activity: predicting behavior relating to cognitive
      workload.
AB  - INTRODUCTION: The focus of this study was to examine oculomotor behavioral
      changes while subjects performed auditory and driving tasks. METHODS: There were
      13 participants who completed 3 10-min tasks consisting of driving only, the
      Paced Auditory Serial Addition Task (PASAT) only, and a dual task of both driving
      and auditory tasks. For each participant, changes in six measures were assessed
      as a function of cognitive workload, specifically changes in eye activity,
      including blink frequency, blink duration, fixation frequency, fixation duration,
      pupil diameter, and horizontal vergence. In addition, deviations in lateral lane
      position were assessed as a measure of driving behavior. RESULTS: Compared with
      the subjects' behavior in the driving-only task, results showed an increase in
      blink frequency during the combined driving and auditory task. Also, during the
      dual task the mean pupil diameter and horizontal vergence increased when subjects
      performed well in the auditory task in contrast to when the subjects performed
      poorly. Evidence of visual tunneling or reduced range of scanning and decreases
      in rearview mirror and odometer glances appeared when subjects performed the
      driving and auditory dual task. There was no significant change in fixation
      frequency. However, decreased fixation duration appeared to predict upcoming
      errors in the auditory task. Pupil diameter changes were significantly higher
      when performing well on the auditory task than when subjects were performing
      poorly. CONCLUSION: Eye behavior trends reported in this study may provide
      insight to human behavior corresponding with cognitive workload, which may in
      turn be utilized to produce reliable workload indicators and applications that
      predict poor performance in real time.

PMID- 17547319
TI  - Multisensory cueing for enhancing orientation information during flight.
AB  - The U.S. Air Force still regards spatial disorientation (SD) and loss of
      situational awareness (SA) as major contributing factors in operational Class A
      aircraft mishaps ($1M in aircraft loss and/or pilot fatality). Air Force Safety
      Agency data show 71 Class A SD mishaps from 1991-2004 in both fixed and rotary
      wing aircraft. These mishaps resulted in 62 fatalities and an aircraft cost of
      over $2.OB. These losses account for 21 % of the USAF's Class A mishaps during
      that 14-yr period. Even non-mishap SD events negatively impact aircrew
      performance and reduce mission effectiveness. A multisensory system has been
      developed called the Spatial Orientation Retention Device (SORD) to enhance the
      aircraft attitude information to the pilot. SORD incorporates multisensory aids
      including helmet mounted symbology and tactile and audio cues. SORD has been
      prototyped and demonstrated in the Air Force Research Laboratory at Wright
      Patterson AFB, OH. The technology has now been transitioned to a Rotary Wing
      Brownout program. This paper discusses the development of SORD and a potential
      application, including an augmented cognition application. Unlike automatic
      ground collision avoidance systems, SORD does not take over the aircraft if a pre
      set altitude is broached by the pilot; rather, SORD provides complementary
      attitude cues to the pilot via the tactile, audio, and visual systems that allow
      the pilot to continue flying through disorienting conditions.

PMID- 17547320
TI  - Operational neuroscience: neurophysiological measures in applied environments.
AB  - There is, without question, an interest within the military services to
      understand, account for, and adapt to the cognitive state of the individual
      warfighter. As the field of neuroscience has matured through investments from
      numerous government agencies, we are on the cusp of being able to move
      confidently from the lab into the field--and deepen our understanding of the
      cognitive issues embedded in the warfighting environment. However, as we edge
      closer to this integration--it is critical for researchers in this arena to
      understand the landscape they are entering-reflected not only in the challenges
      of each task or operational environment but also in the individual differences
      intrinsic to each warfighter. The research papers in this section cover this
      spectrum, including individual differences and their prediction of adaptability
      to high-stress environments, the influence of sleep-deprivation on
      neurophysiological measures of stimulus categorization, neurophysiological
      measures of stress in the training environment and, finally, real-time neural
      measures of task engagement, mental workload and vigilance. It is clear from this
      research, and other work detailed in this supplement, that the judicious use of
      neuroscience, cognitive psychology, and physiology in the applied environment is
      desirable for both researchers and operators. In fact, we suggest that these
      investigations merit a field designation unto their own: Operational
      Neuroscience. It is our hope that the discussion of this new field of study will
      galvanize others to increase the confidence and utility of this research through
      their own investigations.

PMID- 17547321
TI  - Converging indicators for assessing individual differences in adaptation to
      extreme environments.
AB  - It is well known that microgravity results in various physiological alterations,
      for example, head-ward fluid shifts which can impede physiological adaptation.
      Other factors that may affect crew operational efficiency include disruption of
      sleep-wake cycles, high workload, isolation, confinement, stress, and fatigue.
      From an operational perspective, it is difficult to predict which individuals
      will be most or least affected in this unique environment given that most
      astronauts are first-time flyers. During future lunar and Mars missions space
      crews will include both men and women of multi-national origins, different
      professional backgrounds, and various states of physical condition. Therefore,
      new methods or technologies are needed to monitor and predict astronaut
      performance and health, and to evaluate the effects of various countermeasures on
      crew during long-duration missions. Herein we describe the development and
      validation of a new methodology for assessing the deleterious effects of
      spaceflight on crew health and performance. We reviewed several studies conducted
      in both laboratory and operational environments with men and women ranging in age
      between 18 to 50 yr. The studies included the following: soldiers performing
      command and control functions during mobile operations in enclosed armored
      vehicles; subjects participating in laboratory tests of an anti-motion sickness
      medication; subjects exposed to chronic hypergravity aboard a centrifuge; and
      subject responses to 36-h of sleep deprivation. Physiological measurements,
      performance metrics, and subjective self-reports were collected in each study.
      The results demonstrate that multivariate converging indicators provide a
      significantly more reliable method for assessing environmental effects on
      performance and health than any single indicator.

PMID- 17547322
TI  - The effect of 24-40 hours of sleep deprivation on the P300 response to auditory
      target stimuli.
AB  - INTRODUCTION: Recent studies report lengthening of latency and the reduction of
      amplitude of the P300 component of event-related potentials (ERP) recorded to
      auditory targets following a night of sleep deprivation. However, no study has
      examined whether sleep deprivation impacts the circadian effect on P300. In the
      present study, we examined the impact of 24-40 h of sleep deprivation and of the
      circadian rhythm on the P300. METHODS: There were 18 subjects tested at 08:30,
      14:30, and 21:30 on two different days: once following a night of normal
      nocturnal sleep and once following a night in which subjects did not sleep.
      Behavioral and electrophysiological measures were recorded during each session.
      RESULTS: P300 amplitude was not significantly affected either by sleep
      deprivation or by time of day. However, P300 latency was lengthened by 27 ms
      following sleep deprivation [F (1,14) = 28.55; p < 0.0001]. There was a
      significant interaction between sleep deprivation and circadian rhythm [F (2,13)
      = 3.27; p < 0.05]. When subjects were not sleep deprived, P300 latency was
      decreased during the late evening session. In contrast, when subjects were sleep
      deprived, P300 latency was significantly increased during the 21:30 session. P300
      latency significantly predicted reaction time when subjects were sleep deprived,
      but not when they were not sleep deprived. DISCUSSION: Sleep deprivation impacts
      negatively on the ability to correctly categorize stimuli in discrimination tasks
      especially during the late evening hours. The impact of sleep loss at critical
      hours of the day on cognitive processing should be included in any planning of
      operations requiring speedy and accurate decisions.

PMID- 17547323
TI  - Neurophysiologic methods to measure stress during survival, evasion, resistance,
      and escape training.
AB  - Training in Survival, Evasion, Resistance, and Escape (SERE) is required for U.S.
      military members at high risk of capture. This physically and psychologically
      demanding course is considered an analog to the stress imposed by war, captivity,
      and related events, thus offering a unique and unprecedented medium in which to
      systematically examine human stress and performance during a realistically
      intense operational context. Operational stress is multifaceted, manifesting
      cerebral, neuroendocrine, cardiac, and cognitive characteristics, and
      necessitating an integration of multiple methods of measurement to appropriately
      characterize its complexity. Herein we describe some of our present research
      methods and discuss their applicability to real-time monitoring and predicting of
      key aspects of human performance. A systems approach is taken, whereby some of
      the "key players" implicated in the stress response (e.g., cerebral,
      neuroendocrine, cardiac) are briefly discussed, to which we link corresponding
      investigative techniques (fMRI, acoustic startle eye-blink reflex, heart rate
      variability, and neuroendocrine sampling). Background and previous research with
      each investigative technique and its relationship to the SERE context is briefly
      reviewed. Ultimately, we discuss the operational applicability of each measure,
      that is, how each may be integrated with technologies that allow computational
      systems to adapt to the performer during operational stress.

PMID- 17547324
TI  - EEG correlates of task engagement and mental workload in vigilance, learning, and
      memory tasks.
AB  - INTRODUCTION: The ability to continuously and unobtrusively monitor levels of
      task engagement and mental workload in an operational environment could be useful
      in identifying more accurate and efficient methods for humans to interact with
      technology. This information could also be used to optimize the design of safer,
      more efficient work environments that increase motivation and productivity.
      METHODS: The present study explored the feasibility of monitoring
      electroencephalo-graphic (EEG) indices of engagement and workload acquired
      unobtrusively and quantified during performance of cognitive tests. EEG was
      acquired from 80 healthy participants with a wireless sensor headset (F3-F4,C3
      C4,Cz-POz,F3-Cz,Fz-C3,Fz-POz) during tasks including: multi-level
      forward/backward-digit-span, grid-recall, trails, mental-addition, 20-min 3
      Choice Vigilance, and image-learning and memory tests. EEG metrics for engagement
      and workload were calculated for each 1 -s of EEG. RESULTS: Across participants,
      engagement but not workload decreased over the 20-min vigilance test. Engagement
      and workload were significantly increased during the encoding period of verbal
      and image-learning and memory tests when compared with the recognition/ recall
      period. Workload but not engagement increased linearly as level of difficulty
      increased in forward and backward-digit-span, grid-recall, and mental-addition
      tests. EEG measures correlated with both subjective and objective performance
      metrics. DISCUSSION: These data in combination with previous studies suggest that
      EEG engagement reflects information-gathering, visual processing, and allocation
      of attention. EEG workload increases with increasing working memory load and
      during problem solving, integration of information, analytical reasoning, and may
      be more reflective of executive functions. Inspection of EEG on a second-by
      second timescale revealed associations between workload and engagement levels
      when aligned with specific task events providing preliminary evidence that second
      by-second classifications reflect parameters of task performance.

PMID- 17547325
TI  - Potential paradigm for assessments of biomedical technologies in the operational
      environment.
AB  - The U.S. Army Medical Research and Materiel Command Cognitive Performance,
      Judgment, Decision-making Research Program (CPJDRP) was initiated in part to
      prevent/mitigate performance shortfalls associated with cognitive-psychological
      combat stressors such as workload, fatigue, sleep, and nutritional aspects. An
      Operational Processes and Cognitive Mapping Focus Team (OPCMFT) was established
      for the purposes of integrating laboratory-based research into operational
      environments, embedding metrics into appropriate operational platforms, and
      providing an operational perspective to research that may veer off pragmatic and
      utilitarian courses. The OPCMFT's goal as originally formulated in 2004 was to
      determine operational requirements and test environments for evaluating cognitive
      performance metrics and models, pharmacological countermeasures, and
      neurocognitive monitors for the purpose of sustaining warfighter cognitive
      performance in operational environments (2). This preface first reviews the
      OPCMFT's major deliverables as developed from the CPJDRP workshop in 2005 (6).
      Next, a gap/needs analysis of cognitive research products and test and evaluation
      platforms is presented. Lastly, a summary of each of the three articles-one on
      the role and mitigation of stress, a second on the development of intellectual
      ability norms and statistical methods to interpolate an individual's post-morbid
      capabilities, and a third on a specific measure to assess physiological reactions
      to cognitive stressors--illustrates how each contributes to the effort to help
      improve warfighter cognitive performance. The preface authors emphasize the need
      for an integrated research program focused on the Battle Laboratory (1) with a
      solid infrastructure and an integration of the operational end-user, human
      factors, medical practitioners, and research and development expertise.

PMID- 17547326
TI  - Stress, mental health, and cognition: a brief review of relationships and
      countermeasures.
AB  - Today's network-centric battlefield environment is highly stressful and
      cognitively demanding. Many warfighters are feeling overwhelmed and end up being
      medically evacuated from theater due to mental health problems [i.e., post
      traumatic stress disorder (PTSD) and depression]. Of a sample of troops evacuated
      for psychiatric reasons, 21% (106 out of 509) had psychiatric histories prior to
      deploying to the theater of operations. Most cases were either related to stress
      (i.e., PTSD, n - 33, 310%) or to depression (n = 72, 66%). Stress disorders and
      depression predominate among the psychiatric causes for medical evacuation. This
      review paper discusses stress theories as they pertain to warfighting, the types
      of stress and stress disorders most prevalent on modern battlefields, the
      relationships among stress, psychiatric disease, and cognitive performance, and
      potential methods to decrease some types of stress-related acute and chronic
      disorders (i.e., virtual-reality stress inoculation training).

PMID- 17547327
TI  - The estimated full-scale intellectual abilities of U.S. Army aviators.
AB  - INTRODUCTION: The intellectual abilities of U.S. Army aviators have received a
      paucity of research attention over the years. The resultant lack of idiographic
      and aggregate data on this population has a direct impact on the
      neuropsychologist's ability to make clinical recommendations regarding a return
      to cognitive baseline following a neurological insult. Similarly, no research has
      assessed the generalizability of U.S. Air Force (USAF) research on premorbid
      aviator intellectual abilities to U.S. Army aviators. METHODS: To establish
      estimates of general intellectual abilities in U.S. Army aviators, 1050 rated
      U.S. Army aviators without a head injury history were randomly selected from an
      aeromedical database and coupled with corresponding personnel data that contained
      Armed Services Vocational Aptitude Battery (ASVAB) scores. Estimated Wechsler
      Adult Intelligence Scale-IIII (WAIS-Ill) and Multidimensional Aptitude Battery
      (MAB) full-scale intellectual (FSIQ) abilities were computed. RESULTS: Mean U.S.
      Army aviator intellectual abilities were found to fall in the high average to
      superior range, with a notably large range of scores. Significant differences
      between these results and those of previously published USAF aviators on the MAB
      were found. Significant differences based on gender were absent. Significant
      differences based on rank were found. DISCUSSION: Findings suggest estimated U.S.
      Army aviator intellectual abilities exceed previously published findings, with
      the wide range and non-normal distribution of scores suggesting idiographic
      baseline data would be clinically ideal for today's U.S. Army aviators. Clinical
      and operational benefits of establishing baseline cognitive abilities are
      presented. In the absence of baseline data, estimating the WAIS-III FSIQ score is
      a viable alternative in determining one's premorbid intellectual abilities.

PMID- 17547328
TI  - Field assessment and enhancement of cognitive performance: development of an
      ambulatory vigilance monitor.
AB  - INTRODUCTION: Limited opportunities to study human cognitive performance in non
      laboratory, ambulatory situations exist. However, advances in technology make it
      possible to extend behavioral assessments to the field. One of the first devices
      to measure human behavior in the field was the wrist-worn actigraph. This device
      acquires minute-by-minute information on an individual's physical activity and
      can distinguish sleep from waking, the most basic aspect of behavior. METHODS:
      Our laboratory developed a series of wrist-worn devices, not much larger than a
      watch, which assess reaction time, vigilance and memory. The devices concurrently
      assess motor activity with greater temporal resolution than standard actigraphs.
      They also continuously monitor multiple environmental variables including
      temperature, humidity, sound, and light. RESULTS: These monitors have been
      employed during training and simulated military operations to collect behavioral
      and environmental information that would typically be unavailable under such
      circumstances. Development of the vigilance monitor, and how each successive
      version extended capabilities of the device are described. Data from several
      studies are presented, including studies conducted in harsh field environments
      during a simulated infantry assault, an officer training course. DISCUSSION: The
      monitors simultaneously documented environmental conditions, patterns of sleep
      and activity and effects of nutritional manipulations on cognitive performance.
      They provide a new method to relate cognitive performance to real world
      environmental conditions and assess effects of various interventions on human
      behavior in the field. They can also monitor cognitive performance in real time,
      and if it is degraded, attempt to intervene to maintain

PMID- 17547329
TI  - A new game plan.

PMID- 17547330
TI  - When all else fails.

PMID- 17547331
TI  - Take a number.

PMID- 17547332
TI  - Seal of approval.

PMID- 17547333
TI  - Interpersonal violence in Texas: a physician's role.
AB  - The overall national incidence rates of domestic violence are falling, yet the
      Texas rates are rising and are now twice the national average. Domestic violence,
      now termed intimate-partner violence, affects both men and women of all ages,
      races, and socioeconomic strata. While some risk factors are known, the Texas
      disparities are not yet fully understood. Studies indicate three contributors to
      the national decline: the provision of legal services, improvements in economic
      status, and population aging. Legal action has been shown to decrease repeat
      incidents by 80%. A little known Texas law requires doctors to provide safety and
      shelter information to patients with injuries believed to be caused by family
      violence and to document in the patient's medical record that the information was
      made available to the patient. Our best hope to aid in breaking the cycle of
      violence is to actively screen and distribute safety information to our patients.
      Every physician can ask every patient, "Do you feel safe in your home?"

PMID- 17547334
TI  - Let the family in.

PMID- 17547337
TI  - Parental guidance.

PMID- 17547338
TI  - Bedbugs: an old menace bites back.

PMID- 17547339
TI  - Taking your patient off a ventilator.

PMID- 17547340
TI  - Should the family stay?

PMID- 17547341
TI  - A change of heart: my experience with family presence.

PMID- 17547342
TI  - What it takes to be a leader.

PMID- 17547343
TI  - Interactive teaching: a concept analysis.
AB  - Interactive teaching is conceptually analyzed using the strategies of Walker and
      Avant to promote a common understanding of interactive teaching and to clearly
      explicate interactive teaching characteristics that will foster the construct
      validity of using interactive teaching in pedagogical research. In doing so,
      nurse researchers will be able to better understand and integrate interactive
      teaching into their research protocols, ultimately providing evidence for
      educators to use in determining the most effective teaching methods to
      incorporate into curricula. Interactive teaching is defined and examined using
      relevant sources; related concepts are analyzed and compared with these
      definitions. Antecedents, critical attributes, and consequences of interactive
      teaching are identified and applied in model, borderline, and contrary cases.
      Concluding remarks and suggestions are presented.

PMID- 17547344
TI  - Concept mapping: a nursing model for care planning.
AB  - Concept mapping has many applications and has been used as an effective teaching
      strategy in nursing and other disciplines to evaluate both content knowledge and
      student thinking patterns. Previous applications related to nursing care planning
      usually organize client information around a medical diagnosis. The approach
      described is focused around the reason for nursing care and a holistic nursing
      view of the client, rather than a disease model. Students use a software program
      to cluster and sort assessment data to identify client problems and describe
      relationships between the problems. This results in a nonlinear "picture" of the
      client that can be used for nursing care planning. The process is dynamic and
      flexible, prompting students to identify gaps in information, consider salience,
      and understand the complexity of the particular client situation. It teaches
      critical thinking skills and nursing theory, develops competence with technology,
      and fosters effective interchange between faculty and students.

PMID- 17547345
TI  - Serial concept maps: tools for concept analysis.
AB  - Nursing theory challenges students to think abstractly and is often a difficult
      introduction to graduate study. Traditionally, concept analysis is useful in
      facilitating this abstract thinking. Concept maps are a way to visualize an
      individual's knowledge about a specific topic. Serial concept maps express the
      sequential evolution of a student's perceptions of a selected concept. Maps
      reveal individual differences in learning and perceptions, as well as progress in
      understanding the concept. Relationships are assessed and suggestions are made
      during serial mapping, which actively engages the students and faculty in
      dialogue that leads to increased understanding of the link between nursing theory
      and practice. Serial concept mapping lends itself well to both online and
      traditional classroom environments.

PMID- 17547346
TI  - Learning style preference and student aptitude for concept maps.
AB  - Acknowledging that individuals' preferences for learning vary, faculty in an
      undergraduate nursing program questioned whether a student's learning style is an
      indicator of aptitude in developing concept maps. The purpose of this research
      was to describe the relationship between nursing students' learning style
      preference and aptitude for concept maps. The sample included 120 undergraduate
      students enrolled in the adult health nursing course. Students created one
      concept map and completed two instruments: the Learning Style Survey and the
      Concept Map Survey. Data included Learning Style Survey scores, grade for the
      concept map, and grade for the adult health course. No significant difference was
      found between learning style preference and concept map grades. Thematic analysis
      of the qualitative survey data yielded further insight into students' preferences
      for creating concept maps.

PMID- 17547347
TI  - Concept mapping as a means of course evaluation.
AB  - Concept mapping is a teaching and learning tool that is especially suited for
      science-based instruction. This article describes concept mapping as a tool for
      course evaluation in a fourth-year undergraduate Wellness course in a Health
      Studies Department. Pre-lecture and post-lecture concept maps describing wellness
      were compared on the basis of the degree of complexity of the diagram and the
      relationships among the various parameters. The post-lecture maps showed
      significantly more detail than did the pre-lecture maps, and the complexity of
      the post-lecture maps provided evidence that the students had a clearer
      understanding of all wellness parameters. Compared with a traditional course
      survey, this method detailed what information was important to students in their
      understanding of the course material and provided meaningful feedback on material
      that required greater emphasis in the course. Further research into the use of
      concept mapping to refine evaluative criteria and provide effective teaching is
      recommended.

PMID- 17547348
TI  - A capstone teaching project for undergraduate nursing students: development of a
      visual teaching-learning tool.
AB  - The purpose of this article is to describe an original teaching-learning capstone
      project designed to promote active learning by senior nursing students as they
      transition to professional practice. The centerpiece of the capstone experience
      is the creation of a three-dimensional educational tool called a Visual Project,
      which addresses the learning needs of patients, their families, or the nursing
      staff. Students create their project during the spring semester of their senior
      year, when they are paired with an experienced, baccalaureate-prepared nurse
      preceptor. Students present their projects to both the nursing unit in which they
      worked and the faculty and students of the nursing school. Students consistently
      express a sense of accomplishment when they present their projects and recognize
      that they themselves have undergone the same teaching-learning process that was
      the focus of their project.

PMID- 17547349
TI  - Use of oral examinations to teach concepts of evidence-based practice to nurse
      practitioner students.
AB  - Evidence-based practice has become part of nurse practitioner education. One
      innovative approach to teaching and evaluating evidence-based practice is the
      implementation of oral examinations, in which students orally present their
      review of a research article. Prior to the examination, students are given a
      research article to critique and can prepare for the examination using their
      notes and textbooks. At a scheduled time, they meet with a faculty member to
      respond to both predetermined and unexpected questions requiring critique of the
      research and thorough explanation of how it will (or will not) influence their
      practice. Although this approach may produce anxiety in students, it provides
      another way to evaluate students' ability to communicate about a complex topic
      and is an excellent complementary evaluation method to other approaches, such as
      case studies or written examinations.

PMID- 17547350
TI  - Using the Blackboard platform--more than a course site.

PMID- 17547351
TI  - Intramedullary nailing of proximal femur fractures.
AB  - Despite the general success of the sliding hip screw for stabilization of
      intertrochanteric fractures, there is dissatisfaction with the resultant
      deformity associated with its use, particularly in unstable fracture patterns.
      These concerns have resulted in increasing use of intramedullary devices for
      treatment of peritrochanteric fractures. Use of an intramedullary device for
      peritrochanteric fracture stabilization limits the amount of lag screw sliding
      and resultant limb deformity, particularly shortening, since the fracture can
      settle only until the proximal fragment abuts against the nail. This article
      describes some of the advances in intramedullary nails used to stabilize
      peritrochanteric fractures.

PMID- 17547352
TI  - Osteobiologics.
AB  - Osteobiologic adjuvants that aid in bone grafting have recently been popularized.
      Current osteobiologic technologies can be organized into 3 main categories:
      osteoconductive, osteogenic, and osteoinductive. Appropriate use of osteobiologic
      agents mimics autograft. Compared with autograft , synthetic adjuvants minimize
      donor morbidity. Understanding how synthetic agents can enhance bone formation
      and their appropriate use can aid the orthopedic surgeon in delivering optimal
      care in these difficult cases. The understanding of how synthetic grafts can
      enhance the normal bone healing cascade defines their role and use in treating
      fracture gaps.

PMID- 17547353
TI  - Staged management of tibial plateau fractures.
AB  - Careful and thorough assessment of injury severity, with particular attention
      paid to identifying high-energy injuries, is critical to achieving optimal
      outcomes and avoiding complications following tibial plateau fractures. Staged
      management of tibial plateau fractures refers to the use of temporizing methods
      of care (often spanning external fixation) in high-energy injuries, as well as
      delaying definitive fracture surgery until such a time as the risk of soft tissue
      complications is decreased. This article discusses the principles and techniques
      of staged management, including the use of less invasive methods for definitive
      stabilization.

PMID- 17547354
TI  - What potent blood: non-invasive prenatal genetic diagnosis and the transformation
      of modern prenatal care.

PMID- 17547355
TI  - Some realism about end of life: the current prohibition and the euthanasia
      underground.

PMID- 17547357
TI  - The patentability of the Native Hawaiian genome.

PMID- 17547356
TI  - Merck KGaA v. Integra Lifesciences I, Ltd: implications of the supreme court's
      decision for the people who matter most...the consumer.

PMID- 17547358
TI  - [Retreatment of chronic hepatitis C patients non responder to a previous
      antiviral treatment].
AB  - Treatment of chronic hepatitis C during the past years has shown a significant
      increase of the percentage of therapeutic response, mostly due to the
      availability of pegylated interferons. Nevertheless a proportion of patients,
      ranging from 15% to 60%, do not achieve the virus eradication after treatment,
      largely depending on viral genotype. Retreatment of non responders is recommended
      in those patients who have been treated with non-pegylated interferon. In these
      patients, the rate of antiviral response to retreatment depends on genotype,
      viral load, degree of histological damage, ethnicity and metabolic conditions,
      but also on patients' adherence to the therapy schedule. The probability of a
      sustained virological response after retreatment ranges from 8% to 26%. To
      improve the efficacy of retreatment, either interferon and/or ribavirin dosage
      have been increased, either other antiviral drugs have been added to combination
      therapy. Although these new strategies have produced variable results, they
      remain the cornerstone of retreatment in view of forthcoming new antiviral drugs.

PMID- 17547359
TI  - [Management of pain from osteoporotic vertebral fractures with continuous
      intrathecal administration of morphine].
AB  - Vertebral fractures are the most common consequences of severe osteoporosis. The
      chronic pain from collapse of osteoporotic vertebrae affects quality of life and
      autonomy of patients. The management of pain with oral or transdermal opiates can
      cause severe side-effects. Continuous intrathecal administration of morphine with
      an implantable pump represents a good alternative therapy and has advantages in
      pain relief and quality of life. MATERIALS AND METHODS: We report our experience
      in the treatment of refractory chronic pain due to vertebral fractures using
      pumps for intrathecal infusion of morphine in 24 patients. We administered the
      Visual Analogue Scale (VAS) and the Quality of Life Questionnaire of the European
      Foundation of Osteoporosis (QUALEFFO). RESULTS: A significant pain relief was
      obtained in all implanted patients. Using the QUALEFFO we observed significant
      improvements of all variables such as QDL (quality of life), DW (domestic work),
      ambulation and PHS (perception of health status), before and after 1 year from
      pump implantation. With intrathecal morphine infusion none of the patients
      required additional systemic analgesics. CONCLUSIONS: Our results show that
      intrathecal administration of morphine efficiently relieves the symptoms of pain
      and improve the quality of life. Continuous intrathecal administration of
      morphine represents a good alternative therapy and has advantages in those
      patients who suffer from severe side-effects with systemic administration.

PMID- 17547360
TI  - [Acute renal failure as a complication of transarterial chemoembolization in a
      patient with hepatocellular carcinoma].
AB  - Transarterial chemoembolization (TACE) is included among the wide therapeutic
      tools for the treatment of hepatocellular carcinoma (HCC), tumour with high
      frequency and malignancy. The approach is invasive and, beyond the discomfort for
      the patient, it is charged by a number of side effects and complications. In this
      study we report the case of renal acute failure of hypovolemic origin, as a
      consequence of a TACE in a patient suffering from HCC, occurred after one week of
      intervention. The different possible mechanisms involved in the pathogenesis of
      this complication are discussed.

PMID- 17547361
TI  - [Recent advances in the treatment of the acute hepatitis C].
AB  - Acute hepatitis C is characterized by a frequent evolution in chronic form (70
      85% of cases). The recent literature evidences that Peg-interferon alpha-2b is
      efficacy for the treatment of acute hepatitis C (90% of sustained response).
      Treatment, independently by HCV genotype and baseline viral load, must be
      prolonged for three months and it must be started into three months by onset.

PMID- 17547362
TI  - [Recent advances in the treatment of the hepatitis HBV-related. Effectiveness and
      tolerability of adefovir dipivoxil].
AB  - Adefovir dipivoxil is an analogue nucleotide recently approved for the treatment
      of chronic hepatitis HBV-related. Some recent studies have evidenced that
      treatment with 10 mg/die orally with adefovir dipivoxil is efficacy and well
      tolerate in patients with chronic hepatitis B, both HBeAg-positive and anti-HBe
      positive, with LAM-resistance. Also, adefovir dipivoxil effectively suppresses
      lamivudine-resistant HBV in patients with chronic hepatitis B after liver
      transplantation, compensated or decompensated liver disease and co-infection with
      HIV. Other studies are needed to evaluate the efficacy of prolonged treatment in
      relation to emerge of adefovir-resistant HBV mutants.

PMID- 17547363
TI  - [Physical and psychic elements in chronic pain].
AB  - Chronic pain is a widespread problem in general medicine and in psychiatry. It
      consists in physical and psychic elements. The pain has a specific role, a
      different frequency and a different intensity in each mental illness. Medical
      treatments can get benefit from psychiatric drugs.

PMID- 17547364
TI  - [Management of HCV cirrhosis in patients awaiting liver transplantation and
      prevention of hepatocellular carcinoma].
AB  - HCV correlated chronic hepatophaty represents one of the main causes of cirrhosis
      and, therefore, of orthotopic liver transplantation (OLT). Furthermore, it is
      known how the post-OLT recurrent chronic hepatitis C represents a main cause for
      the re-transplantation. Aim of the present review is the analysis of the natural
      history of HCV cirrhosis and the evaluation of the introduction form in waiting
      list. It has been examined the management of the main complications due to portal
      hypertension in patients awaiting OLT with particular reference to the use of
      TIPS (transjugular intrahepatic porto-systemic stent shunt) and possible
      antiviral treatment to obtain post-OLT HCV negativization. Finally, the problem
      of chemoprevention of hepatocellular carcinoma (HCC) has been considered. As a
      matter of fact, the treatment with Interferon (IFN) has led to undeniable
      benefits. Nevertheless, its use has not lowered the incidence of HCC. Probably,
      such an effect will be reached by means of a maintenance treatment with a small
      weekly dose of Pegylated IFN independently from virological response.

PMID- 17547365
TI  - [Possible causes of oro-facial pain].
AB  - Oral tissue damage and mucositis pain can be a significant problem for patients.
      The frequency and severity of these problems can vary significantly from patient
      to patient. Oral complications primarily are associated with discomfort and
      interference with oral function. Oral tissue damage and pain can result from a
      number of different processes. There are many types of pain and many locations to
      get pain. The body uses pain to tell the brain that something is wrong. Never
      ignore pain. Any type of pain symptom needs prompt professional medical advice
      for diagnosis of the underlying cause of the pain.

PMID- 17547366
TI  - Tagged small molecule library approach for facilitated chemical genetics.
AB  - Chemical genetics is a powerful method which utilizes small molecule regulators
      to reveal the molecular basis of diverse biological processes. However, the
      current chemical genetic approach sometimes meets a serious bottleneck during the
      process of target identification. One faces difficulty in conjugating the active
      compound to an affinity matrix without losing or reducing its activity that leads
      to laborious structure-activity relationship (SAR) studies. To facilitate this
      process, we have developed a tagged triazine library containing a built-in linker
      that provides a straightforward transition from phenotypic screening to target
      identification. A strategy for constructing a tagged library and applications
      with a streamlined target identification and subsequent mechanistic study are
      discussed in this Account.

PMID- 17547367
TI  - Effects of thin-film structural parameters on laser desorption/ionization from
      porous alumina.
AB  - Nanoporous aluminum oxide layers, grown by anodization of aluminum thin films on
      glass and then sputter-coated with gold, were used to study the effects of the
      thin-film structural parameters on laser desorption/ionization (LDI) mass
      spectrometry (MS) of peptides. Variation of MS signal intensity was examined as a
      function of alumina pore depth, pore width, and gold layer thickness. Peptide
      molecular ion intensity was optimal with porous alumina formed from aluminum
      films of approximately 600-nm thickness; thinner or thicker films gave
      significantly lower signals. Signals decreased when pore sizes were increased
      beyond the as-formed width of approximately 100 nm. The MS signal also varied
      with the thickness of the sputtered gold layer with an optimum thickness being
      approximately 90 nm. The results of these studies provide values for empirical
      optimization of LDI MS performance as well as potential clues to the LDI
      mechanism.

PMID- 17547368
TI  - Elucidation of double bond position in unsaturated lipids by ozone electrospray
      ionization mass spectrometry.
AB  - The position(s) of carbon-carbon double bonds within lipids can dramatically
      affect their structure and reactivity and thus has a direct bearing on biological
      function. Commonly employed mass spectrometric approaches to the characterization
      of complex lipids, however, fail to localize sites of unsaturation within the
      molecular structure and thus cannot distinguish naturally occurring regioisomers.
      In a recent communication [Thomas, M. C.; Mitchell, T. W.; Blanksby, S. J. J. Am.
      Chem. Soc. 2006, 128, 58-59], we have presented a new technique for the
      elucidation of double bond position in glycerophospholipids using ozone-induced
      fragmentation within the source of a conventional electrospray ionization mass
      spectrometer. Here we report the on-line analysis, using ozone electrospray mass
      spectrometry (OzESI-MS), of a broad range of common unsaturated lipids including
      acidic and neutral glycerophospholipids, sphingomyelins, and triacylglycerols.
      All lipids analyzed are found to form a pair of chemically induced fragment ions
      diagnostic of the position of each double bond(s) regardless of the polarity, the
      number of charges, or the adduct ion (e.g., [M - H](-), [M - 2H](2-), [M + H](+),
      [M + Na](+), [M + NH(4)](+)). The ability of OzESI-MS to distinguish lipids that
      differ only in the position of the double bonds is demonstrated using the
      glycerophosphocholine standards, GPCho(9Z-18:1/9Z-18:1) and GPCho(6Z-18:1/6Z
      18:1). While these regioisomers cannot be differentiated by their conventional
      tandem mass spectra, the OzESI-MS spectra reveal abundant fragment ions of
      distinctive mass-to-charge ratio (m/z). The approach is found to be sufficiently
      robust to be used in conjunction with the m/z 184 precursor ion scans commonly
      employed for the identification of phosphocholine-containing lipids in shotgun
      lipidomic analyses. This tandem OzESI-MS approach was used, in conjunction with
      conventional tandem mass spectral analysis, for the structural characterization
      of an unknown sphingolipid in a crude lipid extract obtained from a human lens.
      The OzESI-MS data confirm the presence of two regioisomers, namely, SM(d18:0/15Z
      24:1) and SM(d18:0/17Z-24:1), and suggest the possible presence of a third
      isomer, SM(d18:0/19Z-24:1), in lower abundance. The data presented herein
      demonstrate that OzESI-MS is a broadly applicable, on-line approach for structure
      determination and, when used in conjunction with established tandem mass
      spectrometric methods, can provide near complete structural characterization of a
      range of important lipid classes. As such, OzESI-MS may provide important new
      insight into the molecular diversity of naturally occurring lipids.

PMID- 17547369
TI  - Depth analysis of polymer-coated steel samples using near-infrared femtosecond
      laser ablation inductively coupled plasma mass spectrometry.
AB  - The viability of near-infrared femtosecond laser ablation (fs-LA) inductively
      coupled plasma mass spectrometry (ICPMS) for the in-depth analysis of polymer
      coatings over galvanized steel substrates has been studied. A good depth
      resolution was obtained modifying the femtosecond Gaussian beam to a flat-top
      beam by using a liquid-crystal display. In order to avoid mixing of information
      coming from successive shots, a low repetition rate was accomplished and signals
      were monitored shot by shot. Different kinds of coatings were used to demonstrate
      the capability of femtosecond ablation for depth-profiling analysis. Ablation was
      conducted under He atmosphere, after sample cell Ar was admixed. The depth
      profiles obtained by LA-ICPMS are in good agreement with those obtained by GD-OES
      for the three analyzed samples. In cases where due to averaging over several
      millimeter sample roughness determines the depth resolution of GD-OES, it was
      found that LA-ICPMS achieves better depth resolution due to the better lateral
      resolution. The depth resolution obtained by LA-ICPMS was found to be 240 nm and
      2.3 microm, for a hot-dip galvanized steel (HDGS) and a polymer-polymer-coated
      HDGS, respectively, compared to the 2.2 and 4.5 microm achieved with GD-OES for
      the same samples.

PMID- 17547370
TI  - Nanoliter dispensing method by degassed poly(dimethylsiloxane) microchannels and
      its application in protein crystallization.
AB  - This paper describes a method of dispensing a nanoliter volume of liquid into
      arrays of microwells through degassed poly(dimethylsiloxane) (PDMS)
      microchannels. In this method, the PDMS microchannels were reversibly bound to
      arrays of microwells. The PDMS elastomer was predegassed and served as an
      internal vacuum pumping source. Various aqueous solutions were infused into
      arrays of microwells through the reversibly sealed PDMS microchannels. Microwells
      fabricated in PDMS, poly(methyl methacrylate) (PMMA), and glass were all
      compatible with this dispensing method. By removing the PDMS microchannels,
      arrays of droplets confined in the microwells were obtained. Multiplex reaction
      and screening at the nanoliter scale were carried out by binding two such arrays
      of microwells to form microchambers. We applied this method to screening the
      crystallization conditions of four known proteins. Long-term incubation of over 2
      months was achieved by employing glass microwells. An unknown protein was then
      crystallized using the screening method in microwells. The crystals with
      sufficient size were harvested from the reversibly bound microwells. X-ray
      diffraction with a resolution of 3.1 Angstrom was obtained.

PMID- 17547371
TI  - The isolated sixth gelsolin repeat and headpiece domain of villin bundle F-actin
      in the presence of calcium and are linked by a 40-residue unstructured sequence.
AB  - Villin is an F-actin regulating, modular protein with a gelsolin-like core and a
      distinct C-terminal "headpiece" domain. Localized in the microvilli of the
      absorptive epithelium, villin can bundle F-actin and, at higher calcium
      concentrations, is capable of a gelsolin-like F-actin severing. The headpiece
      domain can, in isolation, bind F-actin and is crucial for F-actin bundling by
      villin. While the three-dimensional structure of the isolated headpiece is known,
      its conformation in the context of attachment to the villin core remains
      unexplored. Furthermore, the dynamics of the linkage of the headpiece to the core
      has not been determined. To address these issues, we employ a 208-residue modular
      fragment of villin, D6-HP, which consists of the sixth gelsolin-like domain of
      villin (D6) and the headpiece (HP). We demonstrate that this protein fragment
      requires calcium for structural stability and, surprisingly, is capable of Ca2+
      dependent F-actin bundling, suggesting that D6 contains a cryptic F-actin binding
      site. NMR resonance assignments and 15N relaxation measurements of D6-HP in 5 mM
      Ca2+ demonstrate that D6-HP consists of two independent structural domains (D6
      and HP) connected by an unfolded 40-residue linker sequence. The headpiece domain
      in D6-HP retains its structure and interacts with D6 only through the linker
      sequence without engaging in other interactions. Chemical shift values indicate
      essentially the same secondary structure elements for D6 in D6-HP as in the
      highly homologous gelsolin domain 6. Thus, the headpiece domain of villin is
      structurally and functionally independent of the core domain.

PMID- 17547372
TI  - Destabilization of membranes containing cardiolipin or its precursors by peptides
      derived from mitogaligin, a cell death protein.
AB  - Galig, a gene embedded within the galectin-3 gene, induces cell death when
      transfected in human cells. This death is associated with cell shrinkage, nuclei
      condensation, and aggregation of mitochondria. Galig contains two different
      overlapping open reading frames encoding two unrelated proteins. Previous
      observations have shown that one of these proteins, named mitogaligin, binds to
      mitochondria and promotes the release of cytochrome c. However, the mechanism of
      action of this cytotoxic protein remains still obscure. The present study
      provides evidence that synthetic peptides enclosing the mitochondrial
      localization signal of mitogaligin bind to anionic biological membranes leading
      to membrane destabilization, aggregation, and content leakage of mitochondria or
      liposomes. This binding to anionic phospholipids is the most efficient when
      cardiolipin, a specific phospholipid of mitochondria, is inserted in the
      membranes. Thus, cardiolipin may constitute a target of choice for mitogaligin
      sorting and membrane destabilization activity.

PMID- 17547373
TI  - Probing electrostatic interactions along the reaction pathway of a glycoside
      hydrolase: histidine characterization by NMR spectroscopy.
AB  - We have characterized by NMR spectroscopy the three active site (His80, His85,
      and His205) and two non-active site (His107 and His114) histidines in the 34 kDa
      catalytic domain of Cellulomonas fimi xylanase Cex in its apo, noncovalently aza
      sugar-inhibited, and trapped glycosyl-enzyme intermediate states. Due to
      protection from hydrogen exchange, the level of which increased upon inhibition,
      the labile 1Hdelta1 and 1H epsilon1 atoms of four histidines (t1/2 approximately
      0.1-300 s at 30 degrees C and pH approximately 7), as well as the nitrogen-bonded
      protons in the xylobio-imidazole and -isofagomine inhibitors, could be observed
      with chemical shifts between 10.2 and 17.6 ppm. The histidine pKa values and
      neutral tautomeric forms were determined from their pH-dependent 13C epsilon1-1H
      epsilon1 chemical shifts, combined with multiple-bond 1H delta2/epsilon1-15N
      delta1/epsilon2 scalar coupling patterns. Remarkably, these pKa values span more
      than 8 log units such that at the pH optimum of approximately 6 for Cex activity,
      His107 and His205 are positively charged (pKa > 10.4), His85 is neutral (pKa <
      2.8), and both His80 (pKa = 7.9) and His114 (pKa = 8.1) are titrating between
      charged and neutral states. Furthermore, upon formation of the glycosyl-enzyme
      intermediate, the pKa value of His80 drops from 7.9 to <2.8, becoming neutral and
      accepting a hydrogen bond from an exocyclic oxygen of the bound sugar moiety.
      Changes in the pH-dependent activity of Cex due to mutation of His80 to an
      alanine confirm the importance of this interaction. The diverse ionization
      behaviors of the histidine residues are discussed in terms of their structural
      and functional roles in this model glycoside hydrolase.

PMID- 17547374
TI  - DFT and TD-DFT calculations on the electronic structures and spectroscopic
      properties of cyclometalated platinum(II) complexes.
AB  - The electronic structures and spectroscopic properties of the three tridentate
      cyclometalated Pt(II) complexes Pt(N/?N/?C)C(triple bond)CPh (N/?N/?CH = 6-phenyl
      2,2'-bipyridine) (1), Pt(N/?N/?S)C(triple bond)CPh (N/?N/?SH = 6-thienyl-2,2'
      bipyridine) (2), and Pt(N/?N/?O)C(triple bond)CPh (N/?N/?OH = 6-furyl-2,2'
      bipyridine) (3) were investigated theoretically using the density functional
      theory (DFT) method. The geometric structures of the complexes in the ground and
      excited states were explored at the B3LYP and UB3LYP levels, respectively. The
      absorption and emission spectra of the complexes in CH2Cl2 and CH3CN solutions
      were calculated by time-dependent density functional theory (TD-DFT) with the PCM
      solvent model. The calculated energies of the lowest singlet state and lowest
      triplet state in the three complexes are in good agreement with the results of
      experimental absorption and luminescence studies. All of the lowest-lying
      transitions were categorized as LLCT combined with MLCT transitions. The 623-nm
      emission of 1 from the 3A' --> 1A' transition was assigned as 3LLCT and 3MLCT
      transitions, whereas the 657- and 681-nm emissions of 2 and 3, respectively, were
      attributed to 3ILCT perturbed by 3MLCT transitions. NLO response calculations
      revealed that the nonzero values of the static first hyperpolarizability (beta0)
      for 1-3 are greatly enhanced through the introduction of the metal Pt(II) into
      the cyclometalated ligands, an effect that is determined by MLCT and LLCT
      transitions.

PMID- 17547375
TI  - K-dependent predissociation dynamics of CS2 in the 210-216 nm region.
AB  - The dependence of CS2 predissociation upon rotational quantum number K at
      vibrational levels below the barrier to linearity of the 1B2(1Sigmau+) state has
      been investigated in detail with laser spectroscopy, by using a heated supersonic
      source to increase the intensities of hot band transitions. Predissociation
      lifetimes were determined from rotational contour simulations of 13 vibronic
      bands in the CS photofragment excitation (PHOFEX) spectrum, each terminating at
      the same upper vibrational level but via transitions with different K number (K =
      0, 1, 2, respectively). The rovibrational populations of CS fragment at these
      excitation bands were derived from the laser-induced fluorescence (LIF) spectrum,
      and were used further to obtain the dissociation branching ratios S(1D)/S(3P) as
      well as the excess energy partitionings after dissociation. The lifetimes and the
      branching ratios were found to be sensitively dependent on quantum number K; the
      lifetime decreases with the increase of K, and the branching ratio increases with
      K. Analysis shows that quantum number K influences the S(1D) channel more
      effectively than the S(3P) channel. About 28 and 15% of the total available
      energy is taken up by the CS vibrational and rotational degrees of freedom,
      respectively. Systematic analysis indicates that the two electronic states
      interacting with 1B2(1Sigmau+) state should be bent, and the state correlating
      with S(1D) channel should be more bent.

PMID- 17547376
TI  - The reaction Cl+NO2-->ClONO and ClNO2.
AB  - The extant data (see Int. J. Chem. Kinet. 1984, 16, 1311; Int. J. Chem. Kinet.
      1988, 20, 811; and J. Phys. Chem. 1996, 100, 4019)1-3 for the reaction of Cl
      atoms with NO2 has been examined and compared with calculated values using
      RRKM/ME methods through the use of the coded suite "Multiwell" (see Int. J. Chem.
      Kinet. 2001, 33, 232; MultiWell-2.08 Software; University of Michigan: Ann Arbor,
      MI, 2007; http://aoss.engin.umich.edu/multiwell/)4,5 and ab initio quantum
      calculations in the literature (see J. Phys. Chem. 1994, 98, 111; J. Phys. Chem.
      A 2005, 109, 4736; and Chemphyschem 2004, 5, 1864).6-8 The data are in, or very
      near, the low-pressure limit and therefore sensitive to the density of states of
      the excited ClONO and ClNO2 molecules as well as collisional energy transfer,
      centrifugal effects, and anharmonicity corrections. The data were underpredicted
      by a factor of 2.6 using accepted prescriptions for centrifugal corrections,
      collision frequency, and ignoring anharmonicity. The data could be fit by either
      making all rotational degrees of freedom active or artificially increasing the
      collision frequency, or maybe some of each. This last could also be complemented
      or supplemented by a multiplicative factor ascribed to anharmonicity.

PMID- 17547377
TI  - Calculations of molecular properties in hybrid coupled-cluster and molecular
      mechanics approach.
AB  - We report benchmark calculations obtained with our new coupled-cluster singles
      and doubles (CCSD) code for calculating the first- and second-order molecular
      properties. This code can be easily incorporated into combined [Valiev, M.;
      Kowalski, K. J. Chem. Phys. 2006, 125, 211101] classical molecular mechanics (MM)
      and ab initio coupled-cluster (CC) calculations using NWChem, enabling us to
      study molecular properties in a realistic environment. To test this methodology,
      we discuss the results of calculations of dipole moments and static
      polarizabilities for the Cl2O system in the CCl4 solution using the CCSD (CC with
      singles and doubles) linear response approach. We also discuss the application of
      the asymptotic extrapolation scheme (AES) [Kowalski, K.; Valiev, M. J. Phys.
      Chem. A 2006, 110, 13106] in reducing the numerical cost of CCSD calculations.

PMID- 17547378
TI  - Role of excited core Rydberg states in dissociative recombination.
AB  - Intermediate states formed during the dissociative recombination of molecular
      ions with electrons can play significant roles in determining the magnitude of
      the total rate coefficient. These resonances are Rydberg states of two types,
      that is, they can have the ground or excited states of the ion as a core. Those
      with the excited cores have a fundamentally different excitation mechanism than
      those with the ground state core. The importance of excited core states in
      dissociative recombination has received only limited attention in the literature.
      Theoretical calculations on the dissociative recombination of N2+ are reported
      which compare the two types of resonances. Potential curves, electronic widths,
      cross sections, and rate coefficients are calculated for dissociative
      recombination along the 2(1)Sigma(g)+ state, one of several routes for the
      dissociative recombination of N2+. The ground core resonances, in this example,
      are relatively unimportant compared to those with the excited core. Inclusion of
      the excited core resonances increases the rate coefficient by about a factor of 4
      at room temperature, but the increase is not enough to establish 2(1)Sigma(g)+ as
      the dominant dissociative route.

PMID- 17547379
TI  - Infrared spectra and theoretical calculations of lithium hydride clusters in
      solid hydrogen, neon, and argon.
AB  - A matrix isolation IR study of laser-ablated lithium atom reactions with H2 has
      been performed in solid para-hydrogen, normal hydrogen, neon, and argon. The LiH
      molecule and (LiH)(2,3,4) clusters were identified by IR spectra with isotopic
      substitution (HD, D(2), and H(2) + D(2)) and comparison to frequencies calculated
      by density functional theory and the MP2 method. The LiH diatomic molecule is
      highly polarized and associates additional H(2) to form primary (H(2))(2)LiH
      chemical complexes surrounded by a physical cage of solid hydrogen where the
      ortho and para spin states form three different primary complexes and play a role
      in the identification of the bis-dihydrogen complex and in characterization of
      the matrix cage. The highly ionic rhombic (LiH)(2) dimer, which is trapped in
      solid matrices, is calculated to be 22 kcal/mol more stable than the inverse
      hydrogen bonded linear LiH-LiH dimer, which is not observed here. The cyclic
      lithium hydride trimer and tetramer clusters were also observed. Although the
      spontaneous reaction of 2 Li and H(2) to form (LiH)(2) occurs on annealing in
      solid H(2), the formation of higher clusters requires visible irradiation. We
      observed the simplest possible chemical reduction of dihydrogen using two lithium
      valence electrons to form the rhombic (LiH)(2) dimer.

PMID- 17547380
TI  - Theoretical study of low-spin, high-spin, and intermediate-spin states of
      [Fe(III)(pap)2](+) (pap = N-2-pyridylmethylidene-2-hydroxyphenylaminato).
      Mechanism of light-induced excited spin state trapping.
AB  - The mechanism of light-induced excited spin state trapping (LIESST) of
      [FeIII(pap)2]+ (pap = N-2-pyridylmethylidene-2-hydroxyphenylaminato) was
      discussed on the basis of potential energy surfaces (PESs) of several important
      spin states, where the PESs were evaluated with the DFT(B3LYP) method. The PES of
      the quartet spin state crosses those of the doublet and sextet spin states around
      its minimum. This means that the spin transition occurs from the quartet spin
      state to either the doublet spin state or the sextet spin state around the PES
      minimum of the quartet spin state. The PES minimum of the sextet spin state is
      slightly less stable than that of the doublet spin state by 0.18 eV (4.2
      kcal/mol). This small energy difference is favorable for the LIESST. The doublet
      sextet spin crossover point is 0.41 eV (9.6 kcal/mol) above the PES minimum of
      the sextet spin state. Because of this considerably large activation barrier, the
      thermal spin transition and the tunneling process do not occur easily. In the
      doublet spin state, the ligand to ligand charge transfer (LLCT) transition is
      calculated to be 2.16 eV with the TD-DFT(B3LYP) method, in which the pi orbital
      of the phenoxy moiety and the pi* orbital of the imine moiety in the pap ligand
      participate. This transition energy is moderately smaller than the visible light
      of 550 nm used experimentally. In the sextet spin state, the ligand to metal
      charge transfer (LMCT) transition is calculated to be at 2.36 eV, which is
      moderately higher than the visible light (550 nm). These results indicate that
      the irradiation of the visible light induces the LIESST to generate the sextet
      spin state but the reverse-LIESST is also somewhat induced by the visible light,
      indicating that the complete spin conversion from the doublet spin state to the
      sextet one does not occur, as reported experimentally.

PMID- 17547381
TI  - Excited-state dynamics of donor-acceptor bridged systems containing a boron
      dipyrromethene chromophore: interplay between charge separation and
      reorientational motion.
AB  - The excited-state dynamics of a series of electron donor-acceptor bridged systems
      (DABS) consisting of a boron-dipyrromethene chromophore covalently linked to a
      dinitro-substituted triptycene has been investigated using femtosecond time
      resolved spectroscopy. The chromophores differ by the number of bromine atom
      substituents. The fluorescence lifetime of the DABS without any bromine atom is
      strongly reduced when going from toluene to polar solvents, this shortening being
      already present in chloroform. This effect is about 10 times weaker with a single
      bromine atom and negligible with two bromine atoms on the chromophore. The
      excited-state lifetime shortening is ascribed to a charge transfer from the
      excited chromophore to a nitrobenzene moiety, the driving force of this process
      depending on the number of bromine substituents. The occurrence of this process
      is further confirmed by the investigation of the excited-state dynamics of the
      chromophore alone in pure nitrobenzene. Surprisingly, no correlation between the
      charge separation time constant and the dielectric properties of the solvents
      could be observed. However, a good correlation between the charge separation time
      constant and the diffusional reorientation time of the chromophore alone,
      measured by fluorescence anisotropy, was found. Quantum chemistry calculations
      suggest that quasi-free rotation about the single bond linking the chromophore to
      the triptycene moiety permits a sufficient coupling of the donor and the acceptor
      to ensure efficient charge separation. The charge separation dynamics in these
      molecules is thus controlled by the reorientational motion of the donor relative
      to the acceptor.

PMID- 17547382
TI  - Thermochemistry and accurate quantum reaction rate calculations for H2/HD/D2 +
      CH3.
AB  - Accurate quantum-mechanical results for thermodynamic data, cumulative reaction
      probabilities (for J = 0), thermal rate constants, and kinetic isotope effects
      for the three isotopic reactions H2 + CH3 --> CH4 + H, HD + CH3 --> CH4 + D, and
      D2 + CH3 --> CH(3)D + D are presented. The calculations are performed using flux
      correlation functions and the multiconfigurational time-dependent Hartree (MCTDH)
      method to propagate wave packets employing a Shephard interpolated potential
      energy surface based on high-level ab initio calculations. The calculated
      exothermicity for the H2 + CH3 --> CH4 + H reaction agrees to within 0.2 kcal/mol
      with experimentally deduced values. For the H2 + CH3 --> CH4 + H and D2 + CH3 -->
      CH(3)D + D reactions, experimental rate constants from several groups are
      available. In comparing to these, we typically find agreement to within a factor
      of 2 or better. The kinetic isotope effect for the rate of the H2 + CH3 --> CH4 +
      H reaction compared to those for the HD + CH3 --> CH4 + D and D2 + CH3 --> CH(3)D
      + D reactions agree with experimental results to within 25% for all data points.
      Transition state theory is found to predict the kinetic isotope effect accurately
      when the mass of the transferred atom is unchanged. On the other hand, if the
      mass of the transferred atom differs between the isotopic reactions, transition
      state theory fails in the low-temperature regime (T < 400 K), due to the neglect
      of the tunneling effect.

PMID- 17547383
TI  - Full dimensional quantum calculations of vibrational energies of N-methyl
      acetamide.
AB  - We report quantum calculations of vibrational states of trans N-methyl acetamide
      (H3C-HNCO-CH3) in full dimensionality using the code MULTIMODE. In this code, the
      full potential is represented as a hierarchical sum of n-mode potentials in the
      normal coordinates. All 30 one- and 435 two-mode potentials are included in the
      sum, as well as a restricted set of 10 three-mode potentials corresponding to the
      experimentally probed amide band. The electronic energies on the various n-mode
      grids are obtained using ab initio Moller-Plesset perturbation theory with a
      triple-zeta quality, correlation-consistent basis set. Convergence tests of the
      low-lying vibrational eigenvalues of the amide band show that this limited three
      mode representation of the full potential yields well converged results that are
      in excellent agreement with experiment. The infrared spectrum in the region of
      the amide bands is calculated and also agrees well with experiment.

PMID- 17547384
TI  - Differential and integral cross sections for the H + O2 --> OH + O combustion
      reaction.
AB  - We present accurate differential and integral cross sections for the H + O2 -->
      OH + O reaction obtained on a newly developed ab initio potential energy surface
      using time-independent and time-dependent quantum mechanical methods. The product
      angular distributions near the reaction threshold show pronounced forward and
      backward peaks, reflecting the complex-forming mechanism. However, the asymmetry
      of these peaks suggests certain nonstatistical behaviors, presumably due to some
      relatively short-lived resonances. The integral cross section increases
      monotonically with the collision energy above a reaction threshold.

PMID- 17547385
TI  - De novo design of selective antibiotic peptides by incorporation of unnatural
      amino acids.
AB  - The evolution of drug-resistant bacteria is one of the most critical problems
      facing modern medicine and requires the development of new drugs that exhibit
      their antibacterial activity via novel mechanisms of action. One potential source
      of new drugs could be the naturally occurring peptides that exhibit antimicrobial
      activity via membrane disruption. To develop antimicrobial peptides exhibiting
      increased potency and selectivity against Gram positive, Gram negative, and
      Mycobacterium bacteria coupled with reduced hemolytic activity, peptides
      containing unnatural amino acids have been designed, synthesized, and evaluated.
      These compounds were designed on the basis of the electrostatic surface potential
      maps derived from the NMR determined SDS and DPC micelle-bound conformations of
      (Ala8,13,18)magainin-2 amide. Unnatural amino acids were incorporated into the
      polypeptide backbone to control the structural and physicochemical properties of
      the peptides to introduce organism selectivity and potency. The methods and
      results of this investigation are described below.

PMID- 17547386
TI  - High-throughput synthesis and screening of cyclic peptide antibiotics.
AB  - Cyclic peptides are a rich source of biologically active compounds and are
      produced in nature by plants, bacteria, fungi, and lower sea animals. A high
      throughput methodology has been developed for the combinatorial synthesis,
      screening, and identification of cyclic peptide natural product analogues with
      improved biological activities or useful new activities. The methodology was
      applied to generate a library of 1716 tyrocidine A analogues, which were screened
      for antibacterial activity in 96-well plates. The identity of the active peptides
      was determined by partial Edman degradation/mass spectrometry. This has resulted
      in the discovery of a series of tyrocidine analogues that have significantly
      improved therapeutic indices compared to the natural product. The availability of
      tyrocidine analogues with varying antibacterial activities has provided important
      insights into the structure-function relationship of tyrocidine A, which should
      help reveal its mechanism of action.

PMID- 17547387
TI  - Recursive distance partitioning algorithm for common pharmacophore
      identification.
AB  - An improved method for exhaustively identifying common pharmacophores from a
      given list of 3D conformers is proposed. The method partitions feature lists into
      multidimensional boxes according to the distances between the pharmacophore
      centers. Unlike some existing techniques, each feature list is mapped into
      multiple boxes to ensure that good matches will never be missed due to the
      partitioning. To circumvent the computational complexity of the problem, a
      recursive distance partitioning (RDP) algorithm is introduced, in which the
      partitioning and the elimination of unqualified feature lists are carried out at
      multiple levels. The method is demonstrated to be both accurate and efficient.

PMID- 17547388
TI  - Nonconjugated dendritic iridium(III) complexes with tunable pyridine-based
      ligands: synthesis, photophysical, electrochemical, and electroluminescent
      properties.
AB  - A simple synthetic route was developed for nonconjugated dendritic iridium(III)
      complex based on tunable pyridine-based ligands. From an intermediate 2
      bromopyridyl-4-methanol, three series of polybenzyloxy dendritic pyridine-based
      ligands with 2-phenyl, 2-benzothienyl, and 2,4-difluorophenyl subsitituents were
      easily synthesized via two-step reactions (Suzuki reaction and etherifying
      reaction). Using these pyridine derivatives as the CwedgeN ligands, these
      dendritic iridium(III) complexes exhibiting tunable photoluminescence from blue
      to red were obtained. The photoluminescence quantum yields of these dendritic
      complexes in neat films increased with the increasing generation number of
      dendritic CwedgeN ligands. Importantly, these iridium complexes were used as
      dopants for successfully fabricating polymer-based electrophosphorescent light
      emitting diodes (PLEDs) with the highest external quantum efficiency of 12.8%.

PMID- 17547389
TI  - Cleavage of C-S bonds with the formation of a tetranuclear Cu(I) cluster.
AB  - The treatment of a ligand, 2,6-bis((4-(pyridin-2-yl)pyrimidin-2-ylthio)methyl)-4
      chlorophenol (ClPPT2), with cuprous chloride under a weak base condition led to
      the formation of a neutral CuI4-centered cluster [Cu4(PPT2)4], whose X-ray
      diffraction analysis indicated that C-S bonds of the ligand were cleaved in the
      course of the reaction. To explain the C-S bond cleavage, a reasonable mechanism
      has been proposed. In support of it, four additional ligands, 2,6-bis((4-(pyridin
      2-yl)pyrimidin-2-ylthio)methyl)-4-methylphenol (MePPT2), 2,6-bis((4-(pyridin-3
      yl)pyrimidin-2-ylthio)methyl)-4-methylphenol (MePPT3), 2,6-bis((4-(pyridin-3
      yl)pyrimidin-2-ylthio)methyl)-4-chlorophenol (ClPPT3), and 5-((4-(pyridin-3
      yl)pyrimidin-2-ylthio)methyl)-2-hydroxybenzaldehyde (HBPPT2) were further tested
      to undertake the analogous reaction, and the cleaved products in these
      experiments were detected by electrospray ionization mass spectrometry techniques
      to clarify the process.

PMID- 17547390
TI  - First infrared spectroscopic detection of the monobridged diboranyl radical
      (B2H5, C2v) and its D5-isotopomer in low-temperature diborane ices.
AB  - With the use of a surface-scattering machine, layers of 27+/-4 nm diborane (B2H6)
      frosts were irradiated at 10 K and 10(-10) Torr with energetic electrons. The
      electrons induce a unimolecular decomposition of the diborane molecules and lead
      to boron-hydrogen bond rupture processes. Here, we report the first infrared
      spectroscopic detection of the monobridged diboranyl radical (B2H5, C2v) via the
      nu8 mode at 1033 cm(-1). The infrared assignment of the B2H5 isomer was verified
      by conducting experiments with diborane-d6 (B2D6). Under identical experimental
      conditions, the monobridged B2D5 isomer was observed via the nu6(1154 cm(-1)),
      nu8(823 cm(-1)), and nu5(1307 cm(-1)) absorptions. These data can be utilized in
      future spectroscopic studies of chemical vapor deposition processes to allow an
      identification of the monobridged diboranyl isomer in real time via infrared
      spectroscopy.

PMID- 17547391
TI  - Crystal structures and magnetic and ferroelectric properties of chiral layered
      metal-organic frameworks with dicyanamide as the bridging ligand.
AB  - Two homochiral 2D-layered frameworks composed of a Cu2O2 core and dicyanamide
      (dca) linkers, [Cu((R)-hmp*)(dca)]n (1) and [Cu((S)-hmp*)(dca)]n (2) (hmp*=alpha
      methyl-2-pyridinemethanol), have been synthesized and structurally characterized.
      Preliminary investigations suggest that 1 and 2 show possible ferroelectric
      behaviors. Magnetic studies reveal the existence of strong antiferromagnetic
      interactions between the CuII centers in both complexes. The results demonstrate
      that 1 and 2 are multifunctional material candidates combining ferroelectric and
      antiferromagnetic properties in one molecule.

PMID- 17547392
TI  - A new N,N,O chelate for transition metal chemistry: Fe5 and Fe6 clusters from the
      use of 6-hydroxymethyl-2,2'-bipyridine (hmbpH).
AB  - The initial use of the anion of 6-hydroxymethyl-2,2'-bipyridine (hmbpH) as a
      chelate in coordination chemistry is described. The syntheses, crystal
      structures, and magnetochemical characterization are reported of four new
      iron(III) clusters [Fe5O2(OH)(O2CMe)5(hmbp)3](ClO4)2 (1) and
      [Fe6O2(OH)2(O2CR)6(hmbp)4](NO3)2 (R=Ph (2), Me (3), But (4); hmbpH=6
      hydroxymethyl-2,2'-bipyridine). The reaction of Fe(ClO4)3, hmbpH, and sodium
      acetate in a 1:1: approximately 4 ratio in EtOH gave 1, and the reaction between
      [Fe3O(O2CR)6(H2O)3](NO3) (R=Ph, Me, But) and hmbpH in a 1:1 ratio in MeCN gave 2
      4, respectively. The core of 1 consists of a [Fe4(mu3-O)2]8+ butterfly unit to
      which is attached a fifth Fe atom by bridging O atoms. The core of 2-4 also
      consists of a [Fe4(mu3-O)2]8+ butterfly unit to which are attached an Fe atom on
      either side by bridging O atoms. Variable-temperature (T) and -field (H) solid
      state DC and AC magnetization (M) studies were carried out on complexes 1-4 in
      the 5.0-300 K range. Fitting of the data revealed that 1 has an S=5/2 ground
      state spin whereas 2-4 possess an S=5 ground state. Fitting of the M/NmicroB vs
      H/T data by matrix diagonalization and including only axial zero-field splitting
      (ZFS) gave values of the axial ZFS parameter |D| of 0.75, 0.36, 0.46, and 0.36
      cm(-1) for 1-4, respectively.

PMID- 17547393
TI  - Preparation of Au(I), Ag(I), and Pd(II) N-heterocyclic carbene complexes
      utilizing a methylpyridyl-substituted NHC ligand. formation of a luminescent
      coordination polymer.
AB  - Reaction of the imidazolium N-heterocyclic carbene precursor containing a methyl
      substituted pyridyl functionality [HCH3im(CH3py)]PF6, 1, with Ag2O produces the
      homoleptic Ag(I) complex, [Ag(CH3im(CH3py))2]PF6, 2. In a simple carbene transfer
      reaction the analogous Au(I) species, [Au(CH3im(CH3py))2]PF6, 3, is formed by
      treatment of 2 with Au(tht)Cl in dichloromethane. Both 2 and 3 are structurally
      similar with nearly linearly coordinated NHC ligands. The methyl group appended
      to the pyridyl ring inhibits rotation of the pyridyl group at room temperature.
      Addition of AgBF4 to a hot propionitrile solution of 3 followed by
      crystallization with diethyl ether yields the one-dimensional coordination
      polymer, {[AuAg(CH3im(CH3py))2(NCCH2CH3)](BF4)2}n, 4, which contains Au-Ag
      separations of 2.9845(5) and 2.9641(5) A with intermetallic angles of 167.642(14)
      degrees and 162.081(9) degrees. This material is intensely luminescent in the
      solid state and exhibits an emission band at 453 nm (lambdaex=350 nm). Nearly
      colorless [Pd(CH3im(CH3py))2Cl]PF6, 5, is produced upon treatment of 2 with
      PdCl2(NCC6H5)2. The Pd(II) center in 5 is coordinated to one NHC ligand in a
      chelate fashion, while the second NHC is bound solely through the carbon center.
      The X-ray crystal structures of 1-5 are reported.

PMID- 17547394
TI  - Solvent-dependent resonance Raman spectra of high-valent oxomolybdenum(V)
      tris[3,5-bis(trifluoromethyl)phenyl]corrolate.
AB  - UV-visible, infrared (IR), and resonance Raman (RR) spectra were measured and
      analyzed for a high-valent molybdenum(V)-oxo complex of 5,10,15-tris[3,5
      bis(trifluoromethyl)phenyl]corrole (1) at room temperature. The strength of the
      metal-oxo bond in 1 was found to be strongly solvent-dependent. Solid-state IR
      and RR spectra of 1 exhibited the MoVO stretching vibration at nu(MoVO)=969 cm(
      1). It shifted up by 6 cm(-1) to 975 cm(-1) in n-hexane and then gradually
      shifted to lower frequencies in more polar solvents, down to 960 cm(-1) in
      dimethyl sulfoxide. The results imply that stronger acceptor solvents weaken the
      MoVO bond. The 45-cm(-1) frequency downshifts displayed by 1 containing an 18O
      label in the molybdenum(V)-oxo unit confirmed the assignments for the observed IR
      and RR nu(MoVO) bands. The solvent-induced frequency shift for the nu(MoVO) RR
      band, measured in a series of 25 organic solvents ranging from n-hexane (AN=0.0)
      to N-methylformamide (AN=32.1), did not decrease in direct proportion to
      Gutmann's solvent acceptor numbers (ANs). However, a good linear correlation of
      the nu(MoVO) frequency was found against an empirical "solvent polarity" scale
      (A+B) of Swain et al. J. Am. Chem. Soc. 1983, 105, 502-513. A molecular
      association was observed between chloroform and oxomolybdenum(V) corrole 1
      through MoO...H/CCl3 hydrogen-bonding interactions. This association manifested
      itself as a shift of the nu(MoVO) RR band of 1 in CDCl3 to a higher frequency
      compared to that in CHCl3.

PMID- 17547395
TI  - Technetium fluoride trioxide, TcO3F, preparation and properties.
AB  - TcO4- in HF solution reacts to form Tc3O9F4- along with some TcO3F. Pure TcO3F is
      obtained if a mixture of HF/BiF5 is applied. TcO3F dimerizes in the solid state
      via fluoride bridges, similar to the structures of CrO2F2 and VOF3. TcO3F reacts
      in HF with AsF5 or SbF5 under formation of TcO2F2+As(Sb)F6-.

PMID- 17547396
TI  - Low-valent vanadium oxide nanostructures with controlled crystal structures and
      morphologies.
AB  - Low-valent vanadium oxide nanostructures have been synthesized in large
      quantities using commercial V2O5 powder as the precursor by a facile reduction
      method. The crystal structures and morphologies of vanadium oxide nanostructures
      can be adjusted by altering the concentrations and types of reductants. VO2(B)
      nanostructures are fabricated using oxalic acid as the reductant. VO2(B)
      nanobelts with widths of 80-150 nm, thicknesses of 20-30 nm, and lengths up to
      several micrometers can evolve to olive-like nanostructures composed of
      nanosheets with thicknesses of several nanometers and lateral dimensions of
      several micrometers as the concentration of oxalic acid increases. H2V3O8
      nanobelts with widths of 200-300 nm, thicknesses of 10-20 nm, and lengths up to
      several 10s of micrometers are obtained under the reduction of V2O5 powder with
      ethanol. The belt-shaped morphologies of H2V3O8 are not affected by the
      concentration of ethanol.

PMID- 17547397
TI  - Metallic versus covalent bonding: Ga nanoparticles as a case study.
AB  - A systematic X-ray absorption spectroscopy investigation of the local
      coordination in gallium nanostructures has been performed as a function of
      temperature and particle size. It is shown that the nanostructure strongly
      affects the polymorphism of solid gallium and the (meta)stability range of the
      liquid phase (in agreement with previous works) and that the surface tension acts
      in the same direction as hydrostatic pressure in stabilizing the Ga solid phases.
      The effect of surface free energy is first to favor the metallic arrangement of
      the delta phase and then to stabilize a liquid-like phase based on dimeric
      molecules even at 90 K. The Ga-Ga distance in the dimers is lower in the liquid
      phase than in the alpha solid. The experimental results are discussed in
      comparison with molecular dynamic calculations to assess the presence of covalent
      character of the dimeric Ga2 units in liquid nanostructured gallium.

PMID- 17547398
TI  - "Simulating synthesis": ceria nanosphere self-assembly into nanorods and
      framework architectures.
AB  - We predict, from computer modeling and simulation in partnership with experiment,
      a general strategy for synthesizing spherical oxide nanocrystals via
      crystallization from melt. In particular we "simulate synthesis" to generate full
      atomistic models of undoped and Ti-doped CeO2 nanoparticles, nanorods, and
      nanoporous framework architectures. Our simulations demonstrate, in quantitative
      agreement with experiment [Science 2006, 312, 1504], that Ti (dopant) ions change
      the shape of CeO2 nanocrystals from polyhedral to spherical. We rationalize this
      morphological change by elucidating, at the atomistic level, the mechanism
      underpinning its synthesis. In particular, CeO2 nanocrystals can be synthesized
      via crystallization from melt: as a molten (undoped) CeO2 nanoparticle is cooled,
      nucleating seeds spontaneously evolve at the surface and express energetically
      stable [111] facets to minimize the energy. As crystallization proceeds, the
      [111] facets grow, thus facilitating a polyhedral shape. Conversely, when doped
      with Ti, a (predominantly) TiO2 shell encapsulates the inner CeO2 core. This
      shell inhibits the evolution of nucleating seeds at the surface thus rendering it
      amorphous during cooling. Accordingly, crystallization is forced to proceed via
      the evolution of a nucleating seed in the bulk CeO2 region of the nanoparticle,
      and as this seed grows, it remains surrounded by amorphous ions, which "wrap"
      around the core so that the energies for high-index facets are drastically
      reduced; these amorphous ions adopt a spherical shape to minimize the surface
      energy. Crystallization emanates radially from the nucleating seed, and because
      it is encapsulated by an amorphous shell, the crystallization front is not
      compelled to express energetically favorable surfaces. Accordingly, after the
      nanoparticle has crystallized it retains this spherical shape. A typical
      animation showing the crystallization (with atomistic detail) is available as
      Supporting Information. From this data we predict that spherical oxide
      nanocrystals can be synthesized via crystallization from melt in general by
      suppressing nucleating seed evolution at the surface thus forcing the nucleating
      seed to spontaneously evolve in the bulk. Nanospheres can, similar to zeolitic
      classifications, constitute Secondary Building Units (SBUs) and can aggregate to
      form nanorods and nanoporous framework architectures. Here we have attempted to
      simulate this process to generate models for CeO2 and Ti-doped CeO2 nanorods and
      framework architectures. In particular, we predict that Ti doping will "smooth"
      the surfaces: hexagonal prism shaped CeO2 nanorods with [111] and [100] surfaces
      become cylindrical, and framework architectures change from facetted pores and
      channels with well-defined [111] and [100] surfaces to "smooth" pores and
      channels (expressing both concave and convex curvatures). Such structures are
      difficult to characterize using, for example, Miller indices; rather we suggest
      that these new structural materials may be better described using minimal
      surfaces.

PMID- 17547399
TI  - An experimental and computational approach to defining structure/reactivity
      relationships for intramolecular addition reactions to bicyclic epoxonium ions.
AB  - In this manuscript we report that oxidative cleavage reactions can be used to
      form oxocarbenium ions that react with pendent epoxides to form bicyclic
      epoxonium ions as an entry to the formation of cyclic oligoether compounds.
      Bicyclic epoxonium ion structure was shown to have a dramatic impact on the ratio
      of exo- to endo-cyclization reactions, with bicyclo[4.1.0] intermediates showing
      a strong preference for endo-closures and bicyclo[3.1.0] intermediates showing a
      preference for exo-closures. Computational studies on the structures and
      energetics of the transition states using the B3LYP/6-31G(d) method provide
      substantial insight into the origins of this selectivity.

PMID- 17547400
TI  - Intracrystalline diffusivities and surface permeabilities deduced from transient
      concentration profiles: methanol in MOF manganese formate.
AB  - The intracrystalline concentration profiles during molecular uptake of methanol
      by an initially empty, single crystal of microporous manganese(II) formate
      (Mn(HCO2)2), representing an ionic inorganic-organic hybrid within the MOF
      family, are monitored by interference microscopy. Within these profiles, a
      crystal section could be detected where over the total of its extension (
      approximately 2 microm x 50 microm x 30 microm) molecular uptake ideally followed
      the pattern of one-dimensional diffusion. Analysis of the evolution of
      intracrystalline concentration in this section directly yields the permeability
      of the crystal surface and the intracrystalline diffusivity as a function of the
      concentration of the total range of 0 <or= theta <or= 0.57 covered in the
      experiments. Within this range, the surface permeability is found to increase by
      1 order of magnitude, while, within the limits of accuracy (+/-30%), the
      transport diffusivity remains constant, thus reflecting the properties of the
      lattice gas model.

PMID- 17547401
TI  - Prototypical phosphorus analogues of ethane: general and versatile synthetic
      approaches to hexaalkylated P-P diphosphonium cations.
AB  - Versatile alkylation reactions give access to symmetric, homoleptic nonsymmetric,
      and heteroleptic symmetric hexaalkylated 1,2-diphosphonium derivatives as
      bottleable salts in high yields. A series of 1,2-diphosphonium salts has been
      isolated and characterized, representing prototypical phosphorus analogues of
      ethane. Additionally, the solid-state structures for four derivatives have been
      determined crystallographically. Nonsymmetrically substituted derivatives of 1,2
      diphosphonium cations enable the direct observation of 1J(PAPB) coupling
      constants for two tetracoordinate phosphorus centers. The synthetic approaches
      promise access to a vast array of derivatives and will provide means to the
      systematic development of phosphorus analogues of hydrocarbon chemistry.

PMID- 17547402
TI  - Size-controlled interparticle charge transfer between TiO2 and quantized
      capacitors.

PMID- 17547403
TI  - Decomposition of ruthenium olefin metathesis catalysts.
AB  - The decomposition of a series of ruthenium metathesis catalysts has been examined
      using methylidene species as model complexes. All of the phosphine-containing
      methylidene complexes decomposed to generate methylphosphonium salts, and their
      decomposition routes followed first-order kinetics. The formation of these salts
      in high conversion, coupled with the observed kinetic behavior for this reaction,
      suggests that the major decomposition pathway involves nucleophilic attack of a
      dissociated phosphine on the methylidene carbon. This mechanism also is
      consistent with decomposition observed in the presence of ethylene as a model
      olefin substrate. The decomposition of phosphine-free catalyst
      (H2IMes)(Cl)2Ru=CH(2-C6H4-O-i-Pr) (H2IMes = 1,3-dimesityl-4,5-dihydroimidazol-2
      ylidene) with ethylene was found to generate unidentified ruthenium hydride
      species. The novel ruthenium complex (H2IMes)(pyridine)3(Cl)2Ru, which was
      generated during the synthetic attempts to prepare the highly unstable pyridine
      based methylidene complex (H2IMes)(pyridine)2(Cl)2Ru=CH2, is also reported.

PMID- 17547404
TI  - ClnH6-nSiGe compounds for CMOS compatible semiconductor applications: synthesis
      and fundamental studies.
AB  - We describe the synthesis of a new family of chlorinated Si-Ge hydrides based on
      the formula ClnH6-nSiGe. Selectively controlled chlorination of H3SiGeH3 is
      provided by reactions with BCl3 to produce ClH2SiGeH3 (1) and Cl2HSiGeH3 (2).
      This represents a viable single-step route to the target compounds in commercial
      yields for semiconductor applications. The built-in Cl functionalities are
      specifically designed to facilitate selective growth compatible with CMOS
      processing. Higher order polychlorinated derivatives such as Cl2SiHGeH2Cl (3),
      Cl2SiHGeHCl2 (4), ClSiH2GeH2Cl (5), and ClSiH2GeHCl2 (6) have also been produced
      for the first time leading to a new class of highly reactive Si-Ge compounds that
      are of fundamental and practical interest. Compounds 1-6 are characterized by
      physical and spectroscopic methods including NMR, FTIR, and mass spectroscopy.
      The results combined with first principles density functional theory are used to
      elucidate the structural, thermochemical, and vibrational trends throughout the
      general sequence of ClnH6-nSiGe and provide insight into the dependence of the
      reaction kinetics on Cl content in the products. The formation of 1 was also
      demonstrated by an alternative route based on the reaction of (SO3CF3)SiH2GeH3
      and CsCl. Depositions of 1 and 2 at very low temperatures (380-450 degrees C)
      produce near stoichiometric SiGe films on Si exhibiting monocrystalline
      microstructures, smooth and continuous surface morphologies, reduced defect
      densities, and unusual strain properties.

PMID- 17547405
TI  - One-electron photooxidation and site-selective strand cleavage at 5
      methylcytosine in DNA by sensitization with 2-methyl-1,4-naphthoquinone-tethered
      oligonucleotides.
AB  - Photosensitized one-electron oxidation was applied to discriminate a specific
      base site of 5-methylcytosine (mC) generated in DNA possessing a partial sequence
      of naturally occurring p53 gene, using a sensitizing 2-methyl-1,4-naphthoquinone
      (NQ) chromophore tethered to an interior of oligodeoxynucleotide (ODN) strands.
      Photoirradiation and subsequent hot piperidine treatment of the duplex consisting
      of mC-containing DNA and NQ-tethered complementary ODN led to oxidative strand
      cleavage selectively at the mC site, when the NQ chromophore was arranged so as
      to be in close contact with the target mC. The target mC is most likely to be one
      electron oxidized into the radical cation intermediate by the sensitization of
      NQ. The resulting mC radical cation may undergo rapid deprotonation and
      subsequent addition of molecular oxygen, thereby leading to its degradation
      followed by strand cleavage at the target mC site. In contrast to mC-containing
      ODN, ODN analogs with replacement of normal cytosine, thymine, adenine, or
      guanine at the mC site underwent less amount of such an oxidative strand cleavage
      at the target base site, presumably due to occurrence of charge transfer and
      charge recombination processes between the base radical cation and the NQ radical
      anion. Furthermore, well designed incorporation of the NQ chromophore into an
      interior of ODN could suppress a competitive strand cleavage at consecutive
      guanines, which occurred as a result of positive charge transfer. Thus,
      photosensitization by an NQ-tethered ODN led to one-electron oxidative strand
      cleavage exclusively at the target mC site, providing a convenient method of
      discriminating mC in naturally occurring DNA such as human p53 gene as a positive
      band on a sequencing gel.

PMID- 17547406
TI  - Surface effects on quantum dot-based energy transfer.
AB  - CdSe quantum dot (QD)-phthalocyanine (Pc) conjugates were prepared as energy
      transfer donor-acceptor pairs, and the efficiency of the energy transfer process
      in this system was investigated as a function of QD size and under different
      surface chemistry conditions. The kinetics and efficiency of the energy transfer
      process were studied by femtosecond time-resolved laser spectroscopy. We observed
      that the energy transfer efficiency does not follow a linear dependence on
      spectral overlap integrals as predicted by the Forster theory for molecules. This
      observation is found to be due to the involvement of QD surface states in the
      energy transfer process from the photoexcited QDs to the molecular energy
      acceptor.

PMID- 17547407
TI  - Photogeneration of hydrogen from water using an integrated system based on TiO2
      and platinum(II) diimine dithiolate sensitizers.

PMID- 17547408
TI  - Nanoparticle film charging--ion rectified or ion limited?

PMID- 17547409
TI  - Reversible C-F bond formation and the Au-catalyzed hydrofluorination of alkynes.

PMID- 17547410
TI  - Type-2 isopentenyl diphosphate isomerase. Mechanistic studies with cyclopropyl
      and epoxy analogues.

PMID- 17547411
TI  - Alternating copolymerization of vinyl acetate with carbon monoxide.

PMID- 17547412
TI  - On-demand protection of electrochemical sensors based on adaptive nanowires.

PMID- 17547413
TI  - The highly enantioselective addition of indoles to N-acyl imines with use of a
      chiral phosphoric acid catalyst.
AB  - The highly enantioselective organocatalytic addition of N-benzyl indoles to N
      acyl imines is reported. A total of 15 examples with product yield ranging from
      89% to 99% and enantioselectivities from 90% to 97% are presented. A chiral
      phosphoric acid catalyst derived from a hindered binol derivative was employed
      most effectively in the reaction. Attractive features of the reaction include
      desirable catalyst loadings, good reactivity, generality of substrates, and
      easily removable groups from both nitrogen atoms.

PMID- 17547415
TI  - New indicators of beef sensory quality revealed by expression of specific genes.
AB  - To identify new molecular markers of beef sensory quality, the transcriptomes of
      Longissimus thoracis muscle from 25 Charolais bull calves were analyzed using
      microarrays and compared between high and low meat quality groups; 215 genes were
      differentially expressed according to tenderness, juiciness, and/or flavor. Among
      these, 23 were up-regulated in the tenderest, juiciest, and tastiest meats, and
      18 were highly correlated with both flavor and juiciness (e.g., PRKAG1),
      explaining up to 60% of their variability. Nine were down-regulated in the same
      meats, but only DNAJA1 [the results relating to DNAJA1 and its relationship with
      tenderness have been patented (Genomic marker for meat tenderness; Patent
      EP06300943.5, September 12, 2006)], which encodes a heat shock protein, showed a
      strong negative correlation with tenderness that alone explained 63% of its
      variability. This protein, known for its anti-apoptotic role, could be involved
      in meat aging. Thus, DNAJA1 could constitute a new marker of beef sensory
      quality.

PMID- 17547416
TI  - Inhibition of hemoglobin-mediated oxidation of regular and lipid-fortified washed
      cod mince by a white grape dietary fiber.
AB  - The effectiveness of a white grape dietary fiber concentrate (WGDF) against
      hemoglobin-mediated oxidation of washed cod mince, with and without 10% added
      herring oil, was evaluated during ice storage. WGDF was added at two different
      levels: 2 and 4% based on final weight. An ethanol extract with the ethanol
      extractable polyphenols (EPP) and the ethanol-extracted grape dietary fiber
      residue were also tested as antioxidants in the washed cod mince. The addition of
      WGDF to the model system completely and significantly (p <or= 0.05) inhibited the
      hemoglobin-mediated development of rancid odor during the entire ice storage (10
      days). Thiobarbituric acid reactive substances (TBARS) development and red color
      (a*) losses supported the sensory data. Controls fortified with 10% herring oil
      oxidized at the same rate as oil-free controls and were also significantly
      stabilized by 2% WGDF. The EEP of the WGDF had the same high antioxidant capacity
      as whole WGDF. The ethanol-extracted fiber residue significantly (p <or= 0.05)
      reduced maximum oxidation values obtained for controls by approximately 50% and
      extended the oxidation lag phase by 1 day (p <or= 0.05). Thus, this study showed
      great potential of WGDF to prevent rancidity in fish, mainly due to EPP but also
      due to the ethanol-extracted dietary fiber residue itself.

PMID- 17547417
TI  - Comparison of leaching predictions based on PRZM3.12, LEACHP, and RZWQM98 using
      standard scenario modeling.
AB  - Regulatory agencies in the NAFTA region use ground water leaching models to help
      determine risks to ground water resources. The results of three models for
      leaching predictions are compared using a standard soil and weather scenario
      currently used by the New York Department of Environmental Conservation (NYDEC)
      to simulate the Riverhead soil found on Long Island, New York. The three models,
      PRZM3.12, LEACHP, and RZWQM98, were configured to simulate the behavior of two
      example molecules in corn, turfgrass, and bare soil. For the bare soil
      simulations, LEACHP and RZWQM98 predicted similar peak concentrations and timing
      of peak concentration. Depending on the dissipation rate of the molecule,
      PRZM3.12 predicted similar to reduced peak concentrations due to the delayed
      timing to reach the peak concentration. For the corn and turfgrass simulations,
      peak concentrations and timing to reach peak concentrations varied between the
      models due to differences in how each simulates plant growth and
      evapotranspiration.

PMID- 17547418
TI  - Antibacterial activity of red and white wine against oral streptococci.
AB  - Wine contains a number of biologically active compounds with beneficial effects
      on human health. The antibacterial action of commercial red and white wines
      against oral streptococci responsible for caries development and against S.
      pyogenes responsible for pharyngitis was studied. Its postcontact effect against
      S. mutans was also studied. Both wines displayed activity. The compounds
      responsible for such activities were succinic, malic, lactic, tartaric, citric,
      and acetic acid. The synthetic mixtures of the organic acids tested at the
      concentrations found in wine had greater antibacterial activity than the
      beverages, indicating that in wine they are inhibited by other components. Wine
      polyphenols displayed no activity against oral streptococci or S. pyogenes.
      Findings show that wine is active against oral streptococci and S. pyogenes and
      suggest that it enhances oral health.

PMID- 17547419
TI  - Phenolics in maize genotypes differing in susceptibility to Gibberella stalk rot
      (Fusarium graminearum Schwabe).
AB  - The relationship between phenolic compounds and maize pith resistance to Fusarium
      graminearum, the causal agent of Gibberella stalk rot, was investigated. The
      phenolic acid profiles in the stalks of six maize inbred lines of varying
      susceptibility were evaluated from silking to grain maturity. Four different
      fractions of phenolic compounds were extracted from inoculated and non-inoculated
      (control) pith tissues: insoluble cell-wall-bound, free, soluble ester-bound, and
      soluble glycoside-bound phenolics. Analysis by HPLC revealed that p-coumaric acid
      and ferulic acid were the most abundant compounds in the soluble and cell-wall
      bound fractions. The quantity of free, glycoside-bound, and ester-bound phenolics
      in the pith was lower than the level required for the inhibition of Fusarium
      growth or mycotoxins production; however, significant negative correlations
      between diferulic acid contents in the cell walls and disease severity ratings 4
      days after inoculation were found. The results indicated that future studies
      should focus on the levels of diferulic acids during the early infection process.
      Diferulates may play a role in genotypic resistance of maize to Gibberella stalk
      rot as preformed barriers to infection.

PMID- 17547420
TI  - Characterization of monoclonal antibodies for lead-chelate complexes:
      applications in antibody-based assays.
AB  - Monoclonal antibodies against lead were generated by immunizing BALB/c mice with
      lead conjugated to keyhole limpet hemocyanin (KLH) via a bifunctional chelator, S
      2-(4-aminobenzyl)diethylenetriamine pentaacetic acid (DTPA). Stable hybridoma
      cell lines were produced by fusion of murine splenocytes and SP2/0 myeloma cells.
      One of the hybridomas generated from this fusion (4/7) synthesized and secreted
      an antibody that bound tightly to Pb2+-DTPA complexes but not to metal-free DTPA.
      The performance for a competitive inhibition enzyme-linked immunosorbent assay
      (ELISA) incorporating this antibody was assessed for its sensitivity to changes
      in pH, ionic strength, and blocking reagents. The cross-reactivities in this
      ELISA were less than 3% for Fe3+, Cd2+, Hg2+, and Cu2+ and less than 0.3% for
      Cr3+, Mn2+, Mg2+, In3+, Ag1+, Ni2+, Co2+, Zn2+, Ca2+, Cu1+, and Hg1+. The IC50
      value achieved for lead was 2.72 +/- 0.034 microM, showing the detection range of
      0.092-87.2 microM and the lowest detection limit of 0.056 +/- 0.005 microM.
      Recoveries from the analyte-fortified tap water and ultrapure water were in the
      range of 80-114% . These results indicate that the ELISA could be a convenient
      analytical tool for monitoring lead residues in drinking water.

PMID- 17547421
TI  - The unusal redox centers of SoxXA, a novel c-type heme-enzyme essential for
      chemotrophic sulfur-oxidation of Paracoccus pantotrophus.
AB  - The heterodimeric hemoprotein SoxXA, essential for lithotrophic sulfur oxidation
      of the aerobic bacterium Paracoccus pantotrophus, was examined by a combination
      of spectroelectrochemistry and EPR spectroscopy. The EPR spectra for SoxXA showed
      contributions from three paramagnetic heme iron centers. One highly anisotropic
      low-spin (HALS) species (gmax = 3.45) and two "standard" cytochrome-like low-spin
      heme species with closely spaced g-tensor values were identified, LS1 (gz = 2.54,
      gy = 2.30, and gx = 1.87) and LS2 (gz = 2.43, gy = 2.26, and gx = 1.90). The
      crystal structure of SoxXA from P. pantotrophus confirmed the presence of three
      heme groups, one of which (heme 3) has a His/Met axial coordination and is
      located on the SoxX subunit [Dambe et al. (2005) J. Struct. Biol. 152, 229-234].
      This heme was assigned to the HALS species in the EPR spectra of the isolated
      SoxX subunit. The LS1 and LS2 species were associated with heme 1 and heme 2
      located on the SoxA subunit, both of which have EPR parameters characteristic for
      an axial His/thiolate coordination. Using thin-layer spectroelectrochemistry the
      midpoint potentials of heme 3 and heme 2 were determined: Em3 = +189 +/- 15 mV
      and Em2 = -432 +/- 15 mV (vs NHE, pH 7.0). Heme 1 was not reducible even with 20
      mM titanium(III) citrate. The Em2 midpoint potential turned out to be pH
      dependent. It is proposed that heme 2 participates in the catalysis and that the
      cysteine persulfide ligation leads to the unusually low redox potential (-436
      mV). The pH dependence of its redox potential may be due to (de)protonation of
      the Arg247 residue located in the active site.

PMID- 17547422
TI  - Halide binding by the D212N mutant of Bacteriorhodopsin affects hydrogen bonding
      of water in the active site.
AB  - Bacteriorhodopsin (BR), a membrane protein found in Halobacterium salinarum,
      functions as a light-driven proton pump. The Schiff base region has a quadrupolar
      structure with positive charges located at the protonated Schiff base and Arg82,
      and the counterbalancing negative charges located at Asp85 and Asp212. The
      quadropole inside the protein is stabilized by three water molecules, forming a
      roughly planar pentagonal cluster composed of these waters and two oxygens of
      Asp85 and Asp212 (one from each carboxylate side chain). It is known that BR
      lacks proton-pumping activity if Asp85 or Asp212 is neutralized by mutation, but
      binding of Cl- has different functional effects in mutants at these positions.
      Binding of Cl- to D85T converts into a chloride ion pump (Sasaki, J., Brown, L.
      S., Chon, Y.-S., Kandori, H., Maeda, A., Needleman, R., and Lanyi, J. K. (1995)
      Science 269, 73-75). On the other hand, photovoltage measurements suggested that
      binding of Cl- to D212N restores the proton-pumping activity at low pH (Moltke,
      S., Krebs, M. P., Mollaaghababa, R., Khorana, H. G., and Heyn, M. P. (1995)
      Biophys. J. 69, 2074-2083). In this paper, we studied halide-bound D212N mutant
      BR in detail. Light-induced pH changes in a suspension of proteoliposomes
      containing D212N(Cl-) at pH 5 clearly showed that Cl- restores the proton-pumping
      activity. Spectral blue-shift induced by halide binding to D212N indicates that
      halides affect the counterion of the protonated Schiff base, whereas much smaller
      halide dependence of the lambdamax than in D85T suggests that the binding site is
      distant from the chromophore. In fact, the K minus BR difference Fourier
      transform infrared (FTIR) spectra of D212N at 77 K exhibit little halide
      dependence for vibrational bands of retinal and protein. The only halide
      dependent bands were the C=N stretch of Arg82 and some water O-D stretches,
      suggesting that these groups constitute a halide-binding pocket. A strongly
      hydrogen-bonded water molecule is observed for halide-bound D212N, but not for
      halide-free D212N, which is consistent with our hypothesis that such a water
      molecule is a prerequisite for proton-pumping activity of rhodopsins. We
      concluded that halide binding near Arg82 in D212N restores the water-containing
      hydrogen-bonding network in the Schiff base region. In particular, the ion pair
      formed by the Schiff base and Asp85 through a strongly hydrogen-bonded water is
      essential for the proton-pumping activity of this mutant and may be controlled by
      the halide binding to the distant site.

PMID- 17547423
TI  - Properties of hybridized DNA arrays on single-crystalline undoped and boron-doped
      (100) diamonds studied by atomic force microscopy in electrolytes.
AB  - Properties of hybridized deoxyribonucleic acid (DNA) arrays on single-crystalline
      undoped and boron-doped diamonds are studied at the microscopic level by atomic
      force microscopy (AFM) in buffered electrolytic solutions. DNA is linked to
      diamond via aminodecene molecules (TFAAD) that are attached to undoped diamonds
      by a photochemical reaction and via nitrophenyl-diazonium molecules attached
      electrochemically to boron-doped diamonds. Both H-terminated and oxidized diamond
      surfaces are used in this process. On H-terminated surfaces, AFM measurements
      detect compact DNA layers. By analyzing phase and height contrast in AFM, a DNA
      layer height of 76 A is determined on the photochemically functionalized diamonds
      and a DNA layer height of up to 92 A is determined on the electrochemically
      functionalized diamonds. Based on the layer thickness, the DNA chains are tilted
      under the angle of 31 degrees . The morphology of the DNA layers exhibits long
      range (30-50 nm) undulations of 20 A in height and a nanoroughness of 8 A. Using
      Hertz's model for calculating the contact area of the AFM tip on a DNA layer and
      a geometrical model of DNA arrangement on diamond yields the DNA density on
      diamonds of 6 x 10(12) cm(-2) on both photochemically and electrochemically
      functionalized diamonds. The structure of these dense DNA layers is not
      significantly influenced by variations in buffer salinity of 1-300 mM NaCl. DNA
      molecules can be removed from the diamond surface by contact-mode AFM with forces
      >or= 45 nN and >or= 76 nN on photochemically and electrochemically functionalized
      diamonds, respectively, indicating that DNA is bonded covalently and stronger on
      diamond than on gold substrates. The DNA arrangement and bonding strength are
      similar on oxidized diamond surfaces when using an electrochemical process. On
      oxidized surfaces after photochemical processing, DNA is bonded noncovalently as
      deduced from the removal force < 6 nN. The presence of hybridized DNA as well as
      the selective removal of DNA by AFM scanning are corroborated by fluorescence
      microscopy.

PMID- 17547424
TI  - Electrophoretic transport of latex particles in lipid nanotubes.
AB  - Lipid vesicles can be connected by membrane nanotubes to build networks with
      promising bioanalytical properties. Here we characterize electrophoretic
      transport in such membrane tubes, with a particular eye to how their soft
      material nature influences the intratube migration. In the absence of field, the
      tube radius is 110 +/- 26 nm, and it remains in this range during electrophoresis
      even though the applied electric field causes a slight decrease in the tube
      radius (approximately 6-11%). The electrophoretic velocity of the membrane wall
      (labeled with quantum dots) varies linearly with the field strength. Intratube
      migration is studied with latex spheres of radii 15, 50, 100, and 250 nm. The
      largest particle size does not enter the tube at fields strengths lower than 1250
      V/m because the energy cost for expanding the tube around the particles is too
      high. The smaller particles migrate with essentially the same velocity as the
      membrane at low fields. Above 250 V/cm, the 15 nm particles exhibit an upward
      deviation from linear behavior and in fact migrate faster than in free solution
      whereas the 100 nm particles deviate downward. We propose that these nonlinear
      effects arise because of lipid adsorption to the particles (dominating for 15 nm
      particles) and a pistonlike compression of the solvent in front of the particles
      (dominating for 100 nm). As expected from such complexities, existing theories
      for a sphere migrating in a rigid-wall cylinder cannot explain our velocity
      results in lipid nanotubes.

PMID- 17547425
TI  - Structure-property relationship in stimulus-responsive bolaamphiphile hydrogels.
AB  - The formation of temperature-, concentration-, and pH-responsive hydrogels
      composed of the symmetric long-chain bolaamphiphile dotriacontane-1,1'-diyl
      bis[[2-(dimethylammonio)ethyl]phosphate] (Me(2)PE-C32-Me(2)PE) was investigated
      by rheological, scattering, and spectroscopic techniques. At pH 5, this
      bolaamphiphile is known to form a dense network of helically structured
      nanofibers (Kohler et al. Soft Matter 2006, 2, 77-86). Rheological measurements
      and dynamic light scattering were used to describe the macroscopic behavior of
      the hydrogels. Small-angle neutron scattering (SANS) and time-resolved static
      light scattering were applied to get information about the morphology of the self
      assembled aggregates. Finally, solid-state 31P NMR spectroscopy was used to gain
      insight into the mobility of the bolaamphiphile molecules within the fiber
      aggregates. In comparison with the previously examined trimethylammonio analogue
      PC-C32-PC, which forms temperature-dependent hydrogels, Me(2)PE-C32-Me(2)PE
      exhibits additional concentration- and pH-dependent gelling properties. The
      significantly higher stability of the Me(2)PE-C32-Me(2)PE hydrogel is supported
      by the SANS data, which indicate the presence of fiber aggregates up to 50
      degrees C.

PMID- 17547426
TI  - Liposome layers characterized by quartz crystal microbalance measurements and
      multirelease delivery.
AB  - Intact liposomes have been immobilized onto solid surfaces by a NeutrAvidin
      biotin link. The construction of these layers has been followed up by X-ray
      photoelectron spectroscopy (XPS) and quartz crystal microbalance (QCM)
      measurements with energy dissipation monitoring. Also, the simultaneous release
      of two fluorescent probes from these liposome layers has been investigated with
      the aim to validate this method in multirelease delivery systems. XPS showed the
      successful immobilization of the different layers. XPS results also point out the
      importance of the deactivation method used to reveal the presence of the specific
      NeutrAvidin-biotin attachment. QCM measurements allowed the buildup of the
      different layers to be followed in real time and in situ and suggest that
      biotinylated liposomes stay intact upon surface attachment on NeutrAvidin-covered
      surfaces and had viscoelastic behavior. QCM experiments also demonstrated that
      surface-immobilized liposomes were able to resist irreversible adsorption from
      fetal bovine serum. Release kinetic profiles were studied by monitoring the
      release of two different fluorescent probes, namely, carboxyfluorescein and
      levofloxacin, from these liposome layers. These studies showed that it was
      possible to modulate to some extent the release rates of the two molecules by
      using different configurations of liposome layers.

PMID- 17547427
TI  - Solution-assisted assembly of organic semiconducting single crystals on surfaces
      with patterned wettability.
AB  - Two efficient approaches to assembling organic semiconducting single crystals are
      described. The methods rely on solvent wetting and dewetting on substrates with
      patterned wettability to selectively direct the deposition or removal of organic
      crystals. Substrates were functionalized with different self-assembled monolayers
      (SAMs) to achieve the desired wettabilities. The assembly of different organic
      crystals over centimeter-squared areas on Au, SiO2, and flexible plastic
      substrates was demonstrated. By designing line features on the substrate, the
      alignment of crystals, such as CuPc needles, was also achieved. As a
      demonstration of the potential application of this assembly approach, arrays of
      single-crystal organic field-effect transistors were fabricated by patterning
      organic single crystals directly onto and between transistor source and drain
      electrodes.

PMID- 17547428
TI  - Layered inorganic materials as redox agents: ferrocenium-intercalated zirconium
      phosphate.
AB  - The direct intercalation reaction of ferrocene (bis(eta5
      cyclopentadienyl)iron(II), Fc) with a highly hydrated layered zirconium phosphate
      (ZrP) resulted in the formation of the ferrocenium ion (Fc+) within the ZrP
      material. The Fc+-intercalated ZrP material has an interlayer distance of 10.7 A.
      The intercalated material was used as an electron acceptor for the oxidation of
      both ferro-cytochrome c and the excited state of tris(2,2'
      bipyridine)ruthenium(II) ([Ru(bpy)3]2+). Upon contact of the material with a 1.5
      x 10(-5) M solution of ferro-cytochrome c, the UV-vis absorption spectrum shows
      the successful formation of ferri-cytochrome c. Luminescence spectroscopy shows
      that the Fc+-intercalated ZrP material quenches the luminescence of [Ru(bpy)3]2+.
      The excited-state quenching mechanism of [Ru(bpy)3]2+* by Fc+-intercalated ZrP
      follows a dynamic plus sphere of action model. The second-order dynamic quenching
      rate constant kq is 2.2 x 10(8) M(-1) s(-1).

PMID- 17547429
TI  - Adsorption of bovine serum albumin on template-polymerized
      chitosan/poly(methacrylic acid) complexes.
AB  - Particulate systems composed of polyelectrolyte complexes (PEC) based on chitosan
      and poly(methacrylic acid) were obtained via template polymerization. The
      resultant particles were characterized as having regions with different charge
      densities: chitosan predominating in the core and poly(methacrylic acid) at the
      surface, the particles being negatively charged, as a consequence. Albumin was
      adsorbed on these particles (after cross-linking with glutardialdehyde), and pH
      was controlled to obtain two conditions: (i) adsorption of positively charged
      albumin and (ii) adsorption of albumin at its isoelectric point. Adsorption
      isotherms and zeta-potential measurements showed that albumin adsorption was
      controlled by hydrogen bonding/van der Waals interactions and that brush-like
      structures may enhance the adsorption of albumin on these particles. It was also
      found that shearing can induce desorption of albumin from the PEC surface,
      depending on the continuous phase albumin concentration.

PMID- 17547430
TI  - Interfacial and bulk behavior of sodium dodecyl sulfate in isopropanol-water and
      in isopropanol-poly(vinylpyrrolidone)-water media.
AB  - The surface activity of isopropanol (IP) and poly(vinylpyrrolidone) (PVP) at the
      air/water interface has been studied. The self-aggregation of sodium dodecyl
      sulfate (SDS) in IP-water as well as in IP-PVP-water media has been investigated
      using physical methods, viz., tensiometry, conductometry, calorimetry, and
      viscometry. The interaction of SDS with PVP in IP-water medium as well as its
      self-aggregation (or micellization) in the presence of PVP has been assessed. The
      results reveal a fair degree of surface activity of IP in aqueous medium, which
      is only moderate for PVP. The critical micellar concentration (CMC) of SDS passes
      through a minimum at (v/v) % IP = 6.62. SDS interacts with PVP, yielding a
      critical aggregation concentration (CAC) at a low [SDS], independent of IP
      content in the medium. At a higher [SDS], free micelle formation takes place in
      solution, which is lower in mixed solvent than in water and is independent of
      solvent composition by tensiometry, but not by conductometry and calorimetry. The
      viscosity of micelle-interacted PVP in solution takes a long time to stabilize,
      whereas, for non-interacting additives, such as NaCl and cetyltrimethylammonium
      bromide (CTAB), it is time independent.

PMID- 17547431
TI  - Photografted thin polymer hydrogel layers on PES ultrafiltration membranes:
      characterization, stability, and influence on separation performance.
AB  - Highly fouling-resistant ultrafiltration (UF) membranes were synthesized by
      heterogeneous photograft copolymerization of two water-soluble monomers,
      poly(ethylene glycol) methacrylate (PEGMA) and N,N-dimethyl-N-(2
      methacryloyloxyethyl-N-(3-sulfopropyl)ammonium betaine (SPE), with and without
      cross-linker monomer N,N'-methylene bisacrylamide (MBAA), onto a polyethersulfone
      (PES) UF membrane. The characteristics, the stability, and the UF separation
      performance of the resulting composite membranes were evaluated in detail. The
      membranes were characterized with respect to membrane chemistry (by ATR-IR
      spectroscopy and elemental analysis), surface wettability (by contact angle),
      surface charge (by zeta potential), surface morphology (by scanning electron
      microscopy), and pure water permeability and rejection of macromolecular test
      substances (including the "cutoff" value). The surface chemistry and wettability
      of the composite membranes did not change after incubating in sodium hypochlorite
      solution (typically used for cleaning UF membranes) for a period of 8 days.
      Changes in water permeability after static contact with solutions of a model
      protein (myoglobin) were used as a measure of fouling resistance, and the results
      suggest that PEGMA- and SPE-based composite membranes at a sufficient degree of
      graft modification showed much higher adsorptive fouling resistance than
      unmodified PES membranes of similar or larger nominal cutoff. This was confirmed
      in UF experiments with myoglobin solutions. Similar results, namely, a very much
      improved fouling resistance due to the grafted thin polymer hydrogel layer, were
      also obtained in the UF evaluation using humic acid as another strong foulant. In
      some cases, the addition of the cross-linker during modification could improve
      both permeate flux and solute rejection during UF. Overall, composite membranes
      prepared with an "old generation" nonfouling material, PEGMA, showed better
      performance than composite membranes prepared with a "new generation" one, the
      zwitterionic SPE.

PMID- 17547432
TI  - Pyranine-induced micellization of poly(ethylene glycol)-block-poly(4
      vinylpyridine) and pH-triggered release of pyranine from the complex micelles.
AB  - The pyranine-induced micellization of poly(ethylene glycol)-block-poly(4
      vinylpyridine) (PEG114-b-P4VP61) in aqueous solutions and pH-triggered release of
      pyranine from the complex micelles were studied by dynamic and static light
      scattering, transmission electron microscopy, 1H NMR spectroscopy, and UV-vis
      spectroscopy. At pH 2, the ionized pyranine can ionically cross-link the
      protonated P4VP block and result in well-defined spherical complex micelles with
      a P4VP/pyranine core surrounded by a PEG corona. The ratio of pyranine to pyridyl
      units can influence the structure and the properties of the resultant complex
      micelles. The complex micelles are stable upon dilution and heating but are
      sensitive to pH changes. pH-triggered release of the incorporated pyranine from
      the complex micelles demonstrates that the release behavior is pH-tunable and
      displays good controlled-release characteristics at pH approximately 4.

PMID- 17547433
TI  - Solubilization of n-alkylbenzenes into octaethylene glycol mono-n-tetradecyl
      ether (C14E8) micelles.
AB  - Solubilization of benzene, toluene, ethylbenzene, n-propylbenzene, n
      butylbenzene, and n-pentylbenzene into the micelles of octaethylene glycol
      monotetradecyl ether (C(14)E(8)) was studied, where equilibrium concentrations of
      all the solubilizates were determined spectrophotometrically at 298.2, 303.2, and
      308.2 K. The concentration of the above solubilizates except benzene remained
      constant below the critical micelle concentration (cmc) and increased linearly
      with an increase in C(14)E(8) concentration above the cmc, whereas benzene
      concentration was found to remain constant over the whole concentration range of
      C(14)E(8). The Gibbs energy change (DeltaG(0)) for their solubilization was
      evaluated by the partitioning of the solubilizates between the aqueous phase and
      the micellar phase because of the large aggregation number of the C(14)E(8)
      micelle. Furthermore, enthalpy and entropy changes for their solubilization were
      evaluated from the temperature dependence of the DeltaG(0) values. From these
      thermodynamical parameters and the change in absorption spectra of the
      solubilizates due to their incorporation into the micelles, the solubilization
      site was found to move into the inner core of the micelle with increasing alkyl
      chain length of the solubilizates.

PMID- 17547434
TI  - Surface chemistry and rheology of polysulfobetaine-coated silica.
AB  - We have measured the viscosity of suspensions of colloidal silica particles (d =
      300 nm) and the properties of silica surfaces in solutions of a polymer
      consisting of zwitterionic monomer groups, poly(sulfobetaine methacrylate),
      polySBMA. This polymer has potential use in modifying surface properties because
      the polymer is net uncharged and therefore does not generate double-layer forces.
      The solubility of the polymer can be controlled and varies from poor to good by
      the addition of sodium chloride salt. Ellipsometry was used to demonstrate that
      polySBMA adsorbs to silica and exhibits an increase in surface excess at lower
      salt concentration, which is consistent with a smaller area per molecule at low
      salt concentration. Neutron reflectivity measurements show that the adsorbed
      polymer has a thickness of about 3.7 nm and is highly hydrated. The polymer can
      be used to exercise considerable control over suspension rheology. When silica
      particles are not completely covered in polymer, the suspension produces a highly
      viscous gel. Atomic force microscopy was used to show this is caused by bridging
      of polymer between the particles. At higher surface coverage, the polymer can
      produce either a high or very low viscosity slurry depending on the sodium
      chloride concentration. At high salt concentration, the suspension is stable, and
      the viscosity is lower. This is probably because the entrainment of many small
      ions renders the polymer film highly hydrophilic, producing repulsive surface
      forces and lubricating the flow of particles. At low salt concentrations, the
      polymer is barely soluble and more densely adsorbed. This produces less stable
      and more viscous solutions, which we attribute to attractive interactions between
      the adsorbed polymer layers.

PMID- 17547435
TI  - Bifunctional magnetic-optical nanocomposites: grafting lanthanide complex onto
      core-shell magnetic silica nanoarchitecture.
AB  - A new class of bifunctional architecture combining the useful functions of
      superparamagnetism and terbium complex luminescence into one material has been
      prepared via two main steps by a modified Stober method and the layer-by-layer
      (LbL) assembly technique. The obtained bifunctional nanocomposites exhibit
      superparamagnetic behavior, high fluorescence intensity, and color purity. The
      architecture has been characterized by field-emission scanning electron
      microscopy (FE-SEM), transmission electron microscopy (TEM), UV-vis absorption
      and emission spectroscopy, X-ray diffraction, and superconducting quantum
      interference device (SQUID) magnetometry.

PMID- 17547436
TI  - Micro- and nanopatterned star poly(ethylene glycol) (PEG) materials prepared by
      UV-based imprint lithography.
AB  - A UV-based imprint lithography method is used for the direct surface structuring
      of hydrogel-based biomaterials, which are prepared from a family of tailor-made
      star poly(ethylene glycol) formulations. Bulk star poly(ethylene glycol) (PEG)
      hydrogels are fabricated by cross-linking acrylate-functionalized star PEG
      macromolecules. Cross-linking is achieved by radical reactions initiated by UV
      irradiation. This UV-curable star PEG formulation allows templating of mold
      structures to yield a stable, stand-alone, elastomeric replica of the mold. In
      particular, when a secondary, soft mold is used that consists of a perfluorinated
      elastomer with inherent excellent release properties, nanometer-sized features
      (down to 100 nm) can be imprinted without specialized equipment. The applied UV
      based imprint lithography is a fast and simple technique to employ for the direct
      topographic structuring of bulk PEG-based biomaterials. The UV-based imprinting
      into the star PEG prepolymer by means of a perfluorinated, soft mold can be
      carried out on the bench top, while nanoscale resolution is demonstrated.

PMID- 17547437
TI  - Shared immunoproteome for ovarian cancer diagnostics and immunotherapy: potential
      theranostic approach to cancer.
AB  - Elimination of cancer through early detection and treatment is the ultimate goal
      of cancer research and is especially critical for ovarian and other forms of
      cancer typically diagnosed at very late stages that have very poor response
      rates. Proteomics has opened new avenues for the discovery of diagnostic and
      therapeutic targets. Immunoproteomics, which defines the subset of proteins
      involved in the immune response, holds considerable promise for providing a
      better understanding of the early-stage immune response to cancer as well as
      important insights into antigens that may be suitable for immunotherapy. Early
      administration of immunotherapeutic vaccines can potentially have profound
      effects on prevention of metastasis and may potentially cure through efficient
      and complete tumor elimination. We developed a mass-spectrometry-based method to
      identify novel autoantibody-based serum biomarkers for the early diagnosis of
      ovarian cancer that uses native tumor-associated proteins immunoprecipitated by
      autoantibodies from sera obtained from cancer patients and from cancer-free
      controls to identify autoantibody signatures that occur at high frequency only in
      cancer patient sera. Interestingly, we identified a subset of more than 50
      autoantigens that were also processed and presented by MHC class I molecules on
      the surfaces of ovarian cancer cells and thus were common to the two
      immunological processes of humoral and cell-mediated immunity. These shared
      autoantigens were highly representative of families of proteins with roles in key
      processes in carcinogenesis and metastasis, such as cell cycle regulation, cell
      proliferation, apoptosis, tumor suppression, and cell adhesion. Autoantibodies
      appearing at the early stages of cancer suggest that this detectable immune
      response to the developing tumor can be exploited as early-stage biomarkers for
      the development of ovarian cancer diagnostics. Correspondingly, because the T
      cell immune response depends on MHC class I processing and presentation of
      peptides, proteins that go through this pathway are potential candidates for the
      development of immunotherapeutics designed to activate a T-cell immune response
      to cancer. To the best of our knowledge, this is the first comprehensive study
      that identifies and categorizes proteins that are involved in both humoral and
      cell-mediated immunity against ovarian cancer, and it may have broad implications
      for the discovery and selection of theranostic molecular targets for cancer
      therapeutics and diagnostics in general.

PMID- 17547438
TI  - Identification of proteolytic cleavage sites by quantitative proteomics.
AB  - The identification of natural substrates and their cleavage sites is pivotal to
      defining proteolytic pathways. Here we report a novel strategy for the
      identification of the signature of proteolytic cleavage events based on
      quantitative proteomics. Lysine residues in proteins are blocked by guanidination
      so that free N-terminals can be labeled with amine-specific iTRAQ reagents. The
      quantitative nature of iTRAQ reagents allows us to distinguish N-terminals newly
      formed by proteolytic treatment (neoepitopes) from original N-terminals in
      proteins. Proteins are digested with trypsin and analyzed using MALDI-TOF/TOF
      mass spectrometry. Peptides labeled with iTRAQ reagents are distinguished from
      other peptides by exhibiting intense signature ions in tandem mass spectrometry
      analysis. A corresponding data acquisition strategy was developed to specifically
      analyze iTRAQ tagged N-terminal peptides. To validate the procedure, we examined
      a set of recombinant Escherichia coli proteins that have predicted caspase-3
      cleavage motifs. The protein mixture was treated with active or inactive caspase
      3 and subsequently labeled with two different iTRAQ reagents. Mass spectrometric
      analysis located 10 cleavage sites, all corresponding to caspase-3 consensus.
      Spiking caspase-cleaved substrate into a human cell lysate demonstrated the high
      sensitivity of the procedure. Moreover, we were able to identify proteolytic
      cleavage products associated with the induction of cell-free apoptosis. Together,
      these data reveal a novel application for iTRAQ technology for the detection of
      proteolytic substrates.

PMID- 17547439
TI  - Complexation of phenols by calix[4]arene Diethers in a low-permittivity solvent.
      Self-switched complexation by 25,27-Dibenzyloxycalix[4]arene.
AB  - To improve the selectivity of sensing, the thermodynamics of the complex
      formation of some calix[4]arene hosts with neutral phenol guests was studied in
      carbon tetrachloride as nonpolar solvent. The molecular shape of calixarenes was
      varied by the selective functionalization with tBu and O-CH2-Ph (O-benzyl) or OPr
      groups at the upper and lower rim, respectively. To vary the electron density on
      the guest's aromatic rings, the parent phenol was functionalized in the para
      position with electron-withdrawing Cl, as well as H, and electron-releasing CH3
      and tBu groups. To study the interaction between calixarene and the guests, PL
      and quantum-chemical methods were applied. The results revealed an overall 1:1
      complex stoichiometry except for the parent dibenzyloxycalix[4]arene, where 1:2
      host-guest stoichiometries were observed irrespective of the quality of phenol.
      In the latter case, the complex formation shows a self-switched character: the
      first phenol molecule is included in the calixarene cavity, and only afterward, a
      second guest molecule is bound by the two benzyloxy aromatics. Although the
      enthalpy change predicts strong interaction between the host and the guest, the
      Gibbs free energy change of the complex formation is small, resulting in a
      relatively low complex stability. The solvent-relaxation measurements support
      that the unexpected entropy change could be the consequence of the reorientation
      of solvent molecules around the calixarene building block. The reorientation is
      assisted by dispersive forces between solute and solvent molecules. IR and RAMAN
      analysis of the complexes exclude a considerable participation of the phenolic OH
      group in the stabilization of the complex. This result is in agreement with
      earlier findings where deterministic role of pi-pi interaction in the complex
      stability was assumed.

PMID- 17547440
TI  - Determination of charge and molecular weight of rigid-rod polyelectrolytes.
AB  - Rod-like polyelectrolytes are an interesting model system because their
      persistence length is independent of the ionic strength and pH of the surrounding
      medium and they permit the investigation of polyelectrolytes in the absence of
      conformational degrees of freedom. In this work, rigid-rod poly(aramide)
      polyelectrolytes were synthesized by the Higashi method. Electrophoresis NMR
      spectroscopy in conjunction with diffusion NMR spectroscopy has been applied to
      determine the effective charge of the polymer. The charge was determined from the
      balance between the force in the electric field and the hydrodynamic friction in
      the steady-state electrophoretic motion. Because only organic counterions were
      present, and were identified in the proton NMR spectra, the counterions were
      investigated as well, and the fraction of condensed counterions was determined
      directly. From the effective charge per molecule and the knowledge of the
      fraction of condensed counterions, the total charge per molecule was determined.
      Finally, from the total charge, the number of repeat units and thus the molecular
      weight were inferred.

PMID- 17547441
TI  - Cellular interaction of different forms of aluminum nanoparticles in rat alveolar
      macrophages.
AB  - Nanomaterials, with dimensions in the 1-100 nm range, possess numerous potential
      benefits to society. However, there is little characterization of their effects
      on biological systems, either within the environment or on human health. The
      present study examines cellular interaction of aluminum oxide and aluminum
      nanomaterials, including their effect on cell viability and cell phagocytosis,
      with reference to particle size and the particle's chemical composition.
      Experiments were performed to characterize initial in vitro cellular effects of
      rat alveolar macrophages (NR8383) after exposure to aluminum oxide nanoparticles
      (Al2O3-NP at 30 and 40 nm) and aluminum metal nanoparticles containing a 2-3 nm
      oxide coat (Al-NP at 50, 80, and 120 nm). Characterization of the nanomaterials,
      both as received and in situ, was performed using transmission electron
      microscopy (TEM), dynamic light scattering (DLS), laser Doppler velocimetry
      (LDV), and/or CytoViva150 Ultra Resolution Imaging (URI)). Particles showed
      significant agglomeration in cell exposure media using DLS and the URI as
      compared to primary particle size in TEM. Cell viability assay results indicate a
      marginal effect on macrophage viability after exposure to Al2O3-NP at doses of
      100 microg/mL for 24 h continuous exposure. Al-NP produced significantly reduced
      viability after 24 h of continuous exposure with doses from 100 to 250 microg/mL.
      Cell phagocytotic ability was significantly hindered by exposure to 50, 80, or
      120 nm Al-NP at 25 microg/mL for 24 h, but the same concentration (25 microg/mL)
      had no significant effect on the cellular viability. However, no significant
      effect on phagocytosis was observed with Al2O3-NP. In summary, these results show
      that Al-NP exhibit greater toxicity and more significantly diminish the
      phagocytotic ability of macrophages after 24 h of exposure when compared to Al2O3
      NP.

PMID- 17547442
TI  - Plum-pudding gels as a platform for drug delivery: understanding the effects of
      the different components on the diffusion behavior of solutes.
AB  - The internal structure of composite gels made of responsive microgel particles
      inserted into a bulk hydrogel (N-isopropylacrylamide microgel particles in a
      cross-linked dimethylacrylamide matrix) has been investigated from the diffusion
      behavior of poly(ethylene glycol) (PEG) probes through the network, in the
      absence of specific interactions between the diffusing molecules and the system.
      The effect of the different components has been examined, for example, the size
      of the probe, the bulk structure, and the microgel nature. Particles were
      characterized prior to their insertion into the hydrogel in order to describe
      their properties as a function of size and cross-linker content, thus revealing
      different swelling behaviors. The biggest effects on the diffusion of the PEG
      probes were related to the bulk structure, and no major effects were registered
      by the addition of different microgels into the hydrogel network. We attempt to
      rationalize this behavior in terms of the composite gel structure and discuss the
      results in terms of their meaning for controlled drug delivery strategies.

PMID- 17547443
TI  - Structural investigations on the hydrolysis and condensation behavior of pure and
      chemically modified alkoxides. 2. Germanium alkoxides.
AB  - Structural investigations on the hydrolysis and condensation behavior of
      germanium alkoxides were for the first time performed by means of X-ray
      absorption fine structure and Raman spectroscopy. The studies reveal that
      germanium alkoxides are monomeric in nature and undergo very fast hydrolysis and
      condensation reactions upon water addition. However, the chelation of germanium
      alkoxides by acetylacetone does not take place even 48 h after mixing, and any
      change in hydrolysis and condensation behavior is not observed after
      acetylacetone addition. When mixed with prehydrolyzed silicon alkoxide, the
      structures of germanium alkoxides are not modified. Both Si and Ge precursors are
      insensitive to the presence of each other in the reaction solution even after 48
      h of aging. The addition of water to this mixture catalyzes the hydrolysis and
      condensation reactions very fast and leads to the formation of Ge-O-Ge (and
      consequently Si-O-Si) homocondensation products.

PMID- 17547444
TI  - Simulation of heme using DFT + U: a step toward accurate spin-state energetics.
AB  - We investigate the DFT + U approach as a viable solution to describe the low
      lying states of ligated and unligated iron heme complexes. Besides their central
      role in organometallic chemistry, these compounds represent a paradigmatic case
      where LDA, GGA, and common hybrid functionals fail to reproduce the experimental
      magnetic splittings. In particular, the imidazole pentacoordinated heme is
      incorrectly described as a triplet by all usual DFT flavors. In this study, we
      show that a U parameter close to 4 eV leads to spin transitions and molecular
      geometries in quantitative agreement with experiments and that DFT + U represents
      an appealing tool in the description of iron porphyrin complexes, at a much
      reduced cost compared to correlated quantum-chemistry methods. The possibility of
      obtaining the U parameter from first principles is explored through a self
      consistent linear-response formulation. We find that this approach, which proved
      to be successful in other iron systems, produces in this case some overestimation
      with respect to the optimal values of U.

PMID- 17547445
TI  - Structural investigations on the hydrolysis and condensation behavior of pure and
      chemically modified alkoxides. 1. Transition metal (Hf and Ta) alkoxides.
AB  - Structural investigations on the hydrolysis and condensation behavior of hafnium
      and tantalum alkoxides were for the first time performed by means of X-ray
      absorption fine structure and Raman spectroscopy. The studies reveal that both of
      the alkoxides are dimeric in nature and instantaneously undergo hydrolysis and
      condensation reactions upon the addition of water. The results indicate that the
      chemical reaction of the alkoxides with acetylacetone occurs immediately with an
      increase from 6- to 8-fold coordination around the metal. As a consequence of the
      coordination by a bidentate ligand, hydrolysis and condensation reactions are
      hindered in solutions of the chemically modified Hf(OnBu)4 and Ta(OEt)5.
      Furthermore, the investigations demonstrate that the structure of metal alkoxides
      is not altered after mixing with prehydrolyzed silicon tetraethoxide, and even
      after 48 h, both of the species remain as separate entities in the mixture. The
      addition of water to this mixture starts the hydrolysis and condensation
      reactions instantaneously and leads to the formation of a M-O-M homocondensation
      product due to the different reactivity of the two alkoxides.

PMID- 17547446
TI  - ESR studies of poly(aniline-co-m-aminophenol) in the solid state and nonaqueous
      solution.
AB  - The copolymers, poly(aniline-co-m-aminophenol)s, used for the ESR studies were
      synthesized chemically in the solutions consisting of different concentration
      ratios of m-aminophenol to aniline. On the basis of the ESR measurements, the
      unpaired spin (polaron) densities of the copolymers were calculated to be 1.14 x
      10(19) spins per gram for copolymer-A with the conductivity of 7.02 x 10(-6) S cm
      1 and 2.03 x 10(20) spins per gram for copolymer-C with the conductivity of 2.34
      S cm-1. The ESR measurements of the copolymers in the solid states show that the
      peak-to-peak line width DeltaHpp decreases with a decreasing concentration ratio
      of m-aminophenol to aniline, but the g-value hardly changes. A conversion of
      Curie spins to Pauli spins for the copolymers is observed as the temperature
      changes in going from low temperature to high temperature between 136 and 356 K.
      The ESR studies of the copolymers in a nonaqueous solution first reveal that
      there are two free radicals in the copolymer, and the unpaired spins in the
      copolymers arise from nitrogen nuclei.

PMID- 17547447
TI  - Measuring conformational dynamics: a new FCS-FRET approach.
AB  - Fluorescence correlation spectroscopy (FCS) has recently emerged as a powerful
      technique to study conformational dynamics of biomolecules, but often its
      applicability is limited by the difficulty of separating the contributions of
      kinetics from those due to diffusion. We present a new approach based on the
      simultaneous analysis of the auto- and cross-correlation functions of the
      intensities measured in two independent detectors for a donor-acceptor labeled
      biomolecule. Fluctuations in fluorescence intensity are a consequence of
      diffusion and the variations in fluorescence resonance energy transfer (FRET)
      efficiency due to changes in donor-acceptor distance. Although the complete
      description of the correlation functions requires that diffusion is well
      characterized, the ratio of any two correlation functions depends on kinetic
      parameters only. This provides a means by which kinetic information can be
      obtained independently of the diffusion contributions. As proof of principle, we
      reanalyze data obtained in previous work with nucleosomes. In contrast to our
      previous work, where a donor-only sample was used to characterize diffusion, we
      now show that the same kinetic information can be obtained from a single
      experiment with a double-labeled biomolecule. This eliminates not only the need
      of a reference, but also artifacts associated with changes in the observation
      volume between measurements.

PMID- 17547448
TI  - Sugar radicals formed by photoexcitation of guanine cation radical in
      oligonucleotides.
AB  - This work presents evidence that photoexcitation of guanine cation radical (G+*)
      in dGpdG and DNA-oligonucleotides TGT, TGGT, TGGGT, TTGTT, TTGGTT, TTGGTTGGTT,
      AGA, and AGGGA in frozen glassy aqueous solutions at low temperatures leads to
      hole transfer to the sugar phosphate backbone and results in high yields of
      deoxyribose radicals. In this series of oligonucleotides, we find that G+* on
      photoexcitation at 143 K leads to the formation of predominantly C5'* and C1'*
      with small amounts of C3'*. Photoconversion yields of G+* to sugar radicals in
      oligonucleotides decreased as the overall chain length increased. However, for
      high molecular weight dsDNA (salmon testes) in frozen aqueous solutions,
      substantial conversion of G+* to C1'* (only) sugar radical is still found (ca.
      50%). Within the cohort of sugar radicals formed, we find a relative increase in
      the formation of C1'* with length of the oligonucleotide, along with decreases in
      C3'* and C5'*. For dsDNA in frozen solutions, only the formation of C1'* is found
      via photoexcitation of G+*, without a significant temperature dependence (77-180
      K). Long wavelength visible light (>540 nm) is observed to be about as effective
      as light under 540 nm for photoconversion of G+* to sugar radicals for short
      oligonucleotides but gradually loses effectiveness with chain length. This
      wavelength dependence is attributed to base-to-base hole transfer for wavelengths
      >540 nm. Base-to-sugar hole transfer is suggested to dominate under 540 nm. These
      results may have implications for a number of investigations of hole transfer
      through DNA in which DNA holes are subjected to continuous visible illumination.

PMID- 17547449
TI  - Thermodynamic studies of aqueous and CCl4 solutions of 15-crown-5 at 298.15 K: an
      application of McMillan-Mayer and Kirkwood-Buff theories of solutions.
AB  - The density and osmotic coefficient data for solutions of 15-crown-5 (15C5) in
      water and in CCl4 solvent systems at 298.15 K have been reported using techniques
      of densitometry and vapor pressure osmometry in the concentration range of 0.01-2
      mol kg-1. The data are used to obtain apparent molar and partial molar volumes,
      activity coefficients of the components as a function of 15C5 concentration.
      Using the literature heat of dilution data for aqueous system, it has become
      possible to calculate entropy of mixing (DeltaS(mix)), excess entropy of solution
      (DeltaS(E)), and partial molar entropies of the components at different
      concentrations. The results of all these are compared to those obtained for
      aqueous 18-crown-6 solutions reported earlier. It has been observed that the
      partial molar volume of 15C5 goes through a minimum and that of water goes
      through a maximum at approximately 1.2 mol kg(-1) in aqueous solutions whereas
      the opposite is true in CCl4 medium but at approximately 0.5 mol kg(-1). The
      osmotic and activity coefficients of 15C5 and excess free energy change for
      solution exhibit distinct differences in the two solvent systems studied. These
      results have been explained in terms of hydrophobic hydration and interactions in
      aqueous solution while weak solvophobic association of 15C5 molecules in CCl4
      solutions is proposed. The data are further subjected to analysis by applying
      McMillan-Mayer and Kirkwood-Buff theories of solutions. The analysis shows that
      osmotic second virial coefficient value for 15C5 is marginally less than that of
      18C6 indicating that reduction in ring flexibility does not affect the energetics
      of the interactions much in aqueous solution while the same gets influenced much
      in nonpolar solvent CCl4.

PMID- 17547450
TI  - Role of B800 in carotenoid-bacteriochlorophyll energy and electron transfer in
      LH2 complexes from the purple bacterium Rhodobacter sphaeroides.
AB  - The role of the B800 in energy and electron transfer in LH2 complexes has been
      studied using femtosecond time-resolved transient absorption spectroscopy. The
      B800 site was perturbed by application of lithium dodecyl sulfate (LDS), and
      comparison of treated and untreated LH2 complexes from Rhodobacter sphaeroides
      incorporating carotenoids neurosporene, spheroidene, and spheroidenone was used
      to explore the role of B800 in carotenoid to bacteriochlorophyll-a (BChla) energy
      transfer and carotenoid radical formation. Efficiencies of the S1-mediated energy
      transfer in the LDS-treated complexes were 86, 61, and 57% in the LH2 complexes
      containing neurosporene, spheroidene, and spheroidenone, respectively. Analysis
      of the carotenoid S1 lifetimes in solution, LDS-treated, and untreated LH2
      complexes allowed determination of B800/B850 branching ratio in the S1-mediated
      energy transfer. It is shown that B800 is a major acceptor, as approximately 60%
      of the energy from the carotenoid S1 state is accepted by B800. This value is
      nearly independent of conjugation length of the carotenoid. In addition to its
      role in energy transfer, the B800 BChla is the only electron acceptor in the
      event of charge separation between carotenoid and BChla in LH2 complexes, which
      is demonstrated by prevention of carotenoid radical formation in the LDS-treated
      LH2 complexes. In the untreated complexes containing neurosporene and
      spheroidene, the carotenoid radical is formed with a time constant of 300-400 fs.
      Application of different excitation wavelengths and intensity dependence of the
      carotenoid radical formation showed that the carotenoid radical can be formed
      only after excitation of the S2 state of carotenoid, although the S2 state itself
      is not a precursor of the charge-separated state. Instead, either a hot S1 state
      or a charge-transfer state lying between S2 and S1 states of the carotenoid are
      discussed as potential precursors of the charge-separated state.

PMID- 17547451
TI  - Chiral discrimination in host-guest supramolecular complexes. Understanding
      enantioselectivity and solid solution behaviors by using spectroscopic methods
      and chemical sensors.
AB  - Diastereomeric host-guest associations formed between permethylated-beta
      cyclodextrin (TMbeta-Cd) and the two enantiomers of p-bromophenylethanol (pBrPE)
      were characterized in aqueous solution by NMR spectroscopy, revealing similar
      inclusion geometries and weak binding constants, whatever the guest
      configuration. These features were confirmed by hydrogenation experiments, and do
      not allow to account for the ability of TMbeta-Cd to resolve racemic pBrPE by
      successive crystallizations [Grandeury, A.; Petit, S.; Gouhier, G.; Agasse, V.;
      Coquerel, G. Tetrahedron: Asymmetry 2003, 14, 2143-2152]. The analysis, by means
      of solid-state NMR, oxidation experiments, and solubility measurements, of the
      two crystalline phases containing known proportions of guest enantiomers revealed
      identical inclusion geometries in a given phase, irrespective of the enantiomeric
      composition. The corresponding solid solutions were further characterized by the
      determination of an isothermal section (40 degrees C) in the relevant ternary
      phase diagram. It appears from all these data that chiral resolution mechanisms
      in this system can only be envisaged in terms of nucleation conditions of each
      crystal form (with its specific inclusion geometry) and enantiomeric recognition
      at crystal solution interfaces during the growth of each crystal packing.

PMID- 17547452
TI  - Limiting partition coefficients of solutes in biphasic
      trihexyltetradecylphosphonium chloride ionic liquid-supercritical CO2 system:
      measurement and LSER-based correlation.
AB  - Limiting partition coefficients of a selection of low-to-medium volatility
      solutes between both phases in a biphasic trihexyltetradecylphosphonium chloride
      ([thtdp][Cl]) ionic liquid (IL)-supercritical carbon dioxide (scCO2) system were
      obtained by capillary column chromatography with [thtdp][Cl] as the stationary
      liquid and scCO2 as the carrier fluid. It is shown that supercritical fluid
      chromatography can be used to probe the partitioning behavior of solutes in
      biphasic IL-scCO2 systems even when the IL has nonzero solubility in scCO2.
      Relative partition coefficients of solutes at a particular temperature and
      density of CO2 can be correlated within Abraham's linear solvation energy
      relationships. Compared with our previous results in a [bmim][BF4]-scCO2 system,
      the solute partition coefficients in the [thtdp][Cl]-scCO2 system are more
      sensitive to the solute hydrogen bond acidity descriptor.

PMID- 17547453
TI  - Damping by bulk and shear viscosity of confined acoustic phonons for
      nanostructures in aqueous solution.
AB  - A nanoparticle in aqueous solution is modeled as a homogeneous elastic isotropic
      continuum sphere in contact with an infinite viscous compressible Newtonian
      fluid. The frequencies and damping of the confined vibrational modes of the
      sphere are calculated for the material parameters of a CdSe nanoparticle in water
      and a poly(methyl methacrylate) nanosphere in water. Although the effects of
      viscosity are found to be negligible for macroscopic objects, for nanoscale
      objects, both the frequency and damping of the vibrational modes are
      significantly affected by the viscosity of the liquid. Furthermore, both shear
      viscosity and bulk viscosity play an important role. A model of the spherical
      satellite tobacco mosaic virus consisting of outer solid layers with a water core
      is also investigated, and the viscosity of the water core is found to
      significantly damp the free vibrational modes. The same approach can be applied
      for nonspherical geometries and also to viscoelastic nanoparticles.

PMID- 17547454
TI  - Conformational behavior of comb-like polyelectrolytes in selective solvent:
      computer simulation study.
AB  - In this work, we present molecular dynamics simulations of comb-like
      polyelectrolytes in selective solvent. The studied polymers have a neutral
      backbone and polyelectrolyte side chains. The solvent is poor for the backbone
      and the theta solvent for the side chains. The polymers are modeled on a coarse
      grained level with implicit solvent. The simulations show that the comb-like
      polyelectrolytes tend to form intramolecular self-organized structures of the
      pearl necklace type. This type of conformational behavior has been predicted by
      Borisov and Zhulina (Borisov, O. V.; Zhulina, E. B. Macromolecules 2005, 38,
      2506) for neutral comb-like copolymers in selective solvent. The present study
      shows that comb-like polyelectrolytes in selective solvent exhibit the same type
      of behavior; however, it can be controlled by one additional parameter, the
      degree of dissociation of the grafts. The local conformational characteristics
      are studied using the ensemble-averaged bond angle cosines as functions of
      monomer position in the chain, which reveal structural details invisible by other
      means.

PMID- 17547455
TI  - Adsorption and hydrolysis reactions of poly(hydroxybutyric acid) depolymerases
      secreted from Ralstonia pickettii T1 and Penicillium funiculosum onto poly[(R)-3
      hydroxybutyric acid].
AB  - Reaction processes of poly[(R)-3-hydroxybutyric acid] (P(3HB)) with two types of
      poly(hydroxybutyric acid) (PHB) depolymerases secreted from Ralstonia pickettii
      T1 and Penicillium funiculosum were characterized by means of atomic force
      microscopy (AFM) and quartz crystal microbalance (QCM). The PHB depolymerase from
      R. pickettii T1 consists of catalytic, linker, and substrate-binding domains,
      whereas the one from P. funiculosum lacks a substrate-binding domain. We
      succeeded in observing the adsorption of single molecules of the PHB depolymerase
      from R. pickettii T1 onto P(3HB) single crystals and the degradation of the
      single crystals in a phosphate buffer solution at 37 degrees C by real-time AFM.
      On the contrary, the enzyme molecule from P. funiculosum was hardly observed at
      the surface of P(3HB) single crystals by real-time AFM, even though the enzymatic
      degradation of the single crystals was surely progressed. On the basis of the AFM
      observations in air of the P(3HB) single crystals after the enzymatic treatments,
      however, not only the PHB depolymerase from R. pickettii T1 but also that from P.
      funiculosum adsorbed onto the surface of P(3HB) crystals, and both concentrations
      of the enzymes on the surface were nearly identical. This means both enzymes were
      adsorbed onto the surface of P(3HB) single crystals. Moreover, QCM measurements
      clarified quantitatively the differences in detachment behavior between two types
      of PHB depolymerases, namely the enzyme from R. pickettii T1 was hardly detached
      but the enzyme from P. funiculosum was released easily from the surface of P(3HB)
      crystals under an aqueous condition.

PMID- 17547456
TI  - Formation of hydroxyapatite provides a tunable protein reservoir within porous
      polyester membranes by an improved soaking process.
AB  - Biomineralization on porous polyester membranes was examined using an improved
      alternate soaking process (ASP). The effect of ion migration for the formation of
      hydroxyapatite (HAp) was shown to be crucial. Ion migration was improved by
      reducing the surface tension by mixing ethanol into an aqueous solution. The
      resulting hybrid materials were evaluated in terms of calcium content; structure
      using scanning electron microscopy (SEM), X-ray diffraction (XRD), and infrared
      spectroscopy (IR); and protein adsorption. The amount of formed HAp was
      controlled by the number of ASP cycles and also through the ethanol content of
      the mixed solvent. As the formation of HAp increased, the formed structure could
      be verified using SEM, IR, and XRD. Protein adsorption was investigated using
      albumin, gamma-globulin, and fibrinogen, and the amount of adsorbed protein was
      well-correlated with that of the formed HAp. This result shows that the total
      amount of the adsorbed proteins can be regulated by the HAp content. In summary,
      a tunable protein reservoir was formed on a porous polyester membrane.

PMID- 17547457
TI  - Vasorelaxant activity of diterpenes from Croton zambesicus and synthetic
      trachylobanes and their structure-activity relationships.
AB  - The diterpenes previously isolated from the leaves of Croton zambesicus were
      tested to evaluate their vasorelaxant activity on the Wistar rat aorta. Their
      vasorelaxant effect was compared to a series of synthetic trachylobanes and
      related polycyclic compounds on KCl- or noradrenaline-induced contractions in
      order to evaluate structure-activity relationships. We demonstrate the
      vasorelaxant properties of some pure trachylobane diterpenes at low concentration
      (IC50 < 10 microM) on KCl-induced contractions, but none have a significant
      effect in noradrenaline-induced contractions. Comparing structures and activity
      we observed that a C-14 carbonyl group associated with a C-15 hydroxy or ketone
      function or a C-3 carbonyl associated with a hydroxymethyl group plays an
      important role in the vasorelaxant activity of trachylobane diterpenes. We also
      observed that the absolute configuration or the cleavage of the C13-C16
      cyclopropane bond does not have a marked effect on the activity. The cytotoxicity
      of all of these compounds has also been evaluated on HeLa cells in order to
      verify that the vasorelaxant activity was not correlated with general
      cytotoxicity.

PMID- 17547458
TI  - Bioactive polyketides from Peperomia duclouxii.
AB  - Four new compounds (1-4) were isolated along with 16 known compounds from whole
      plants of Peperomia duclouxii. The new structures were elucidated as 4-hydroxy-2
      [(3,4-methylenedioxyphenyl)nonanoyl]cyclohexane-1,3-dione (1), 4-hydroxy-2-[(3,4
      methylenedioxyphenyl)undecanoyl]cyclohexane-1,3-dione (2), 4-hydroxy-2-[(3,4
      methylenedioxyphenyl)tridecanoyl]cyclohexane-1,3-dione (3), and 2-[(3,4
      methylenedioxyphenyl)dodecyl]-4-hydroxy-2,3,4,6,7,8-hexahydro-2H-1-benzopyran-5
      one (4), by analysis of their spectroscopic data. The known polyketides, surinone
      A and oleiferinone, showed cell growth inhibitory activity against the WI-38, VA
      13, and HepG2 cell lines with IC50 values that ranged from 4.4 to 9.6 microg/mL.
      The known sesquiterpenoid, sinugibberodiol, showed a more potent effect on
      calcein accumulation than verapamil at 2.5 and 25 microg/mL. Compounds 3 and 4,
      surinone A, and oleiferinone showed moderate to weak inhibitory activity on the
      induction of the intercellular adhesion molecule-1 (ICAM-1) in the presence of IL
      1alpha or TNF-alpha.

PMID- 17547459
TI  - Etnangien, a macrolide-polyene antibiotic from Sorangium cellulosum that inhibits
      nucleic acid polymerases.
AB  - Etnangien (1), a new macrolide antibiotic active against Gram-positive bacteria,
      was isolated from the culture broth of the myxobacterium Sorangium cellulosum,
      strains So ce750 and So ce1045. Spectroscopic structure elucidation of 1 revealed
      a complex macrocyclic lactone bearing a modified C21 carboxylic acid side chain.
      The latter contains two allylic hydroxyl groups and an all-E hexaene unit, which
      provides the characteristic UV chromophore of 1. Initial studies toward the
      mechanism of action showed that bacterial and viral nucleic acid polymerases are
      inhibited by etnangien (1).

PMID- 17547460
TI  - Antiproliferative cardenolides of an Elaeodendron sp. from the Madagascar rain
      forest(1).
AB  - Bioassay-guided fractionation of an ethanol extract obtained from the Madagascar
      plant Elaeodendron sp. led to the isolation of two new cardenolides,
      elaeodendrosides T and U (1 and 2). The structures of the new compounds were
      elucidated using 1D and 2D NMR experiments and mass spectrometry. Compounds 1, 3,
      4, and 5 showed significant antiproliferative activity against A2780 human
      ovarian cancer cells with IC50 values of 0.085, 0.019, 0.19, and 0.10 microM,
      respectively, while compounds 2 and 6 were less active.

PMID- 17547461
TI  - Straightforward methodology for the enantioselective synthesis of benzo[a]- and
      indolo[2,3-a]quinolizidines.
AB  - An enantioselective two-step route to substituted benzo[a]- and indolo[2,3
      a]quinolizidines has been developed. It consists of (i) a stereoselective
      cyclocondensation of a racemic or prochiral delta-oxo(di)ester with either (S)
      (3,4-dimethoxyphenyl)alaninol or (S)-tryptophanol in a process involving a
      dynamic kinetic resolution and/or the differentiation of enantiotopic or
      diastereotopic ester groups, and (ii) a subsequent stereocontrolled cyclization
      on the aromatic ring taking advantage of the masked N-acyl iminium ion present in
      the resulting oxazolopiperidone lactams.

PMID- 17547462
TI  - Synthesis and structure of upper-rim 1,3-alternate
      tetraoxacalix[2]arene[2]triazine azacrowns and change of cavity in response to
      fluoride anion.
AB  - The upper-rim 1,3-alternate tetraoxacalix[2]arene[2]triazine azacrowns were
      constructed effectively by macrocyclic condensation reaction of diamines with
      dichlorinated tetraoxacalix[2]arene[2]triazine intermediates that were
      synthesized from the stepwise fragment coupling reactions of 3,5-dihydroxybenzoic
      acid esters with cyanuric chlorides. Because of the formation of conjugation of
      amino groups with triazine rings, tetraoxacalix[2]arene[2]triazine azacrowns
      existed in a mixture of syn- and anti-isomeric forms. Both fluorescence titration
      and 1H NMR spectroscopic study showed that tetraoxacalix[2]arene[2]triazine
      azacrowns interacted with fluoride anion, leading to cavity changes of the host
      molecules.

PMID- 17547463
TI  - A combinatorial approach to studying the effects of N-alkyl groups on poly(N
      alkyl and N,N-dialkylacrylamide) solubility.
AB  - Soluble polymers including poly(N-alkylacrylamide)s with low mole percent
      loadings of pendant groups are of interest in applications in catalysis,
      synthesis, sequestration, and soluble affinity chromatography where their thermal
      and phase-dependent solubility facilitates purification and separation. This work
      describes a library synthesis and study of the effects of polymer composition on
      the phase-selective solubility of dye-labeled poly(N-n-octadecylacrylamide-co-N-n
      butylacrylamide) copolymers. To study the relative importance of n-octadecyl
      versus n-butyl groups, copolymers with different ratios of n-octadecylacrylamide
      and n-butylacrylamide but with similar degrees of polymerization and
      polydispersity were prepared by a split-pool synthesis using a highly soluble
      poly(N-acryloxy-2-dodecylsuccinimide) as the precursor. Polymer sequestrants were
      used to remove excess amines and the byproduct N-hydroxyl-2-dodecylsuccinimide
      without fractionation of the polyacrylamides. Other studies of dye-labeled
      poly(N,N-dialkylacrylamide)s prepared by the polymerization of N,N
      dialkylacrylamides with methyl, ethyl, propyl, butyl, pentyl, and hexyl N-alkyl
      groups in a variety of thermomorphic or latent biphasic polar/nonpolar solvent
      mixtures showed that poly(N,N-dialkylacrylamide)s like poly(N-alkylacrylamide)s
      have phase-selective solubility that is highly dependent on the size of the N
      alkyl group.

PMID- 17547464
TI  - Chemically induced potential barriers at the carbon nanotube-metal nanoparticle
      interface.
AB  - Single-walled carbon nanotube (SWNT) field effect transistors were
      electrochemically decorated with Pt, Pd, Au, and Ag nanoparticles. Upon exposure
      to 10 ppm NO gas in N2 a trend was found wherein the magnitude of electron
      transfer into the SWNT valence band scaled with the work function of the
      individual metal. This trend gives experimental support for the formation of a
      metal work function dependent potential barrier at the SWNT--nanoparticle
      interface.

PMID- 17547465
TI  - Direct nanoimprinting of metal nanoparticles for nanoscale electronics
      fabrication.
AB  - One-step direct nanoimprinting of metal nanoparticles was investigated to
      fabricate nano-/microscale metallic structures such as nanodot and nanowire
      arrays. This was done at low temperatures and pressures, utilizing the low
      melting temperature and viscosity of metal nanoparticle solutions. Through
      precise control of the fluidic properties of the nanoparticle solution and the
      mold design, high-quality nanoscale features with no or negligible residual layer
      were nanoimprinted. Nanoscale electronic devices were also demonstrated,
      including nanowire resistors and nanochannel organic field effect transistors
      with an air-stable semiconducting polymer.

PMID- 17547466
TI  - Insights on interfacial charge transfer across P3HT/fullerene photovoltaic
      heterojunction from Ab initio calculations.
AB  - The interfacial charge-transfer mechanism of the P3HT/fullerene photovoltaic
      heterojunction is elucidated using density functional theory calculations. Our
      findings indicate that an efficient adiabatic electron transfer is highly
      probable due to the presence of an extended electronic state that has a
      significant probability distribution across the interface in the lowest excited
      state. Furthermore, efficient exciton dissociation is possible because this
      bridging state has significant overlap with near-degenerate unoccupied states
      that are localized on the fullerene.

PMID- 17547469
TI  - Glucocorticoids in the prevention of restenosis after coronary angioplasty:
      therapeutic potential.
AB  - Vessel luminal narrowing after percutaneous coronary intervention (PCI) is
      characterised by platelet aggregation, release of growth factors, inflammatory
      cell infiltration, medial smooth muscle cell (SMC) proliferation, proteoglycan
      deposition and extracellular matrix remodelling. It is broadly accepted that the
      central mechanism at the basis of the whole pathophysiological process of
      restenosis is inflammation, triggered by vascular injury and activated through
      autocrine or paracrine mediators. Glucocorticosteroids exert beneficial effects
      on platelet function, on SMC proliferation and on collagen synthesis as well as
      inflammatory cell migration and activation, thus interfering with several steps
      of the cascade leading to neointima formation and subsequent late lumen loss.
      Initial experiences with systemic administration of glucocorticoids after PCI
      failed to confirm the expected benefits of this treatment, probably as a result
      of inadequate dosage and pharmacokinetic calculations. Recently a short-term,
      high-dose immunosuppressive treatment scheme with oral prednisone has
      demonstrated remarkable clinical and angiographic results when prednisone was
      given orally at a dose of 1 mg/kg for 10 days, 0.5 mg/kg for 20 days and 0.25
      mg/kg for 15 days. This treatment has dramatically reduced the incidence of
      clinical vascular events at 1 year compared with controls (relative risk 0.34;
      95% CI 0.12, 0.96; p = 0.006) and reduced the incidence of angiographic
      restenosis below 10% in different clinical and angiographic subsets. Secondary
      effects of a short course of glucocorticoids are generally minor, predictable and
      reversible: gastric pain, water and salt retention and worsened hypertension
      manifest in nearly 10% of patients. The addition of diuretics and acid
      suppressants before discharge, and the upgrading of antihypertensive medication
      thereafter, if needed, are useful preventive measures to control these temporary
      disorders. A routine blood cell count 4 weeks after PCI is advised in patients
      receiving thienopyridines (clopidogrel or ticlopidine) in addition to prednisone
      to rule out infrequent haematological dyscrasias. Emerging evidence supports this
      strategy as a convenient and well tolerated alternative to more expensive and
      complex revascularisation procedures such as drug eluting stent (DES)
      implantation or cardiac surgery, provided that the treatment is reserved for
      carefully selected candidates, i.e. after the exclusion of those with diabetes
      mellitus, a recent transmural myocardial infarction, or contraindications to the
      administration of a short-course of high-dose glucocorticosteroids. The recent
      concerns regarding the long-term safety of first-generation DES and the as yet
      undetermined duration of dual anti-platelet treatment, further supports the need
      for a simple pharmacological treatment that can be applied in a large percentage
      of patients currently treated with PCI. Multicentre randomised studies aimed at
      defining the efficacy and safety of oral prednisone treatment compared with
      metallic stents and DES are ongoing, and will become available in upcoming years.

PMID- 17547470
TI  - Advanced renal cell carcinoma: current and emerging management strategies.
AB  - Management of renal cell carcinoma (RCC) has made considerable progress in recent
      years, and new emerging strategies are being developed. On the basis of the
      results of two randomised studies in the early 2000s, nephrectomy has now become
      the standard as cytoreductive surgery before embarking on systemic treatment with
      cytokines. Interleukin (IL)-2 and interferon were the standard treatment in
      metastatic RCC (MRCC) until 2006. The efficacy of these two drugs, which have now
      been used for >20 years in MRCC, is still controversial. On the basis of many
      studies, these drugs should not be given to patients with a poor prognosis. In
      patients with good prognostic factors, a cytokine-based regimen should remain the
      standard as either a high-dose IL-2 or subcutaneous regimen. In patients with
      intermediate risk, the results of the French Percy Quattro study encourage the
      use of new targeted therapies as first-line therapy. Development of targeted
      therapies in RCC has been necessary largely because the Von Hippel-Lindau (VHL)
      gene is often mutated in sporadic RCC. VHL protein abnormalities lead to
      accumulation of hypoxia-inducible factor (HIF)-alpha and activation of a series
      of genes, including vascular endothelial growth factor (VEGF), thus inducing
      angiogenesis. Results from many recent studies with new agents that block the
      VEGF pathway have been reported and offer new strategic options for patients with
      MRCC. Sunitinib and sorafenib, two tyrosine kinase inhibitors, improve
      progression-free survival in RCC compared with standard treatment and have been
      recently approved. Temsirolimus, a mammalian target of rapamycin inhibitor
      regulating HIF-alpha, improves survival in RCC patients with poor risk features.
      Bevacizumab, a monoclonal antibody against VEGF, has shown very promising
      efficacy. Overall, treatment of MRCC is currently moving from the cytokine era to
      the targeted agent era. However, many questions still remain regarding the
      efficacy of combination treatments and on the best way to achieve complete
      remission, which is probably the best hope of curing MRCC.

PMID- 17547471
TI  - Antiepileptic drugs in the treatment of neuropathic pain.
AB  - Antiepileptic drugs are an effective treatment for various forms of neuropathic
      pain of peripheral origin, although they rarely provide complete pain relief.
      Multiple multicentre randomised controlled trials have shown clear efficacy of
      gabapentin and pregabalin for postherpetic neuralgia and painful diabetic
      neuropathy. Theses drugs can be rapidly titrated and are well tolerated.
      Topiramate, lamotrigine, carbamazepine and oxcarbazepine are alternatives for the
      treatment of painful diabetic neuropathy, but should be titrated slowly.
      Carbamazepine remains the drug of choice for trigeminal neuralgia; however,
      oxcarbazepine and lamotrigine are potential alternatives. There is an apparent
      need for large-scale randomised controlled trials on the efficacy of
      antiepileptic drugs in neuropathic pain in general, and in cancer-related
      neuropathic pain and neuropathic pain of central origin in particular. Trials
      with long-term follow-up are required to establish the long-term efficacy of
      antiepileptic drugs in neuropathic pain. There is only limited scientific
      evidence to support the idea that drug combinations are likely to be more
      efficacious and safer than each drug alone; further studies are warranted in this
      area.

PMID- 17547472
TI  - The role of NSAIDs in the management of postoperative ophthalmic inflammation.
AB  - Recent advances in cataract surgery, such as phacoemulsification, small-incision
      surgery and advances in foldable intraocular lenses, have resulted in the
      decrease of physical trauma associated with cataract surgery. The decrease in the
      physical surgical trauma decreases the release of prostaglandins, which are the
      main players in postoperative ocular inflammation. However, postoperative
      inflammation continues to be a cause of patient discomfort, delayed recovery and,
      in some cases, suboptimal visual results. Left untreated, this inflammation might
      interfere with patients' rehabilitation and/or contribute to the development of
      other complications, such as cystoid macular oedema.NSAIDs are commercially
      available, in topical or systemic formulations, for the prophylaxis and treatment
      of ocular conditions. Topically applied NSAIDs are commonly used in the
      management and prevention of non-infectious ocular inflammation and cystoid
      macular oedema following cataract surgery. They are also used in the management
      of pain following refractive surgery and in the treatment of allergic
      conjunctivitis. Despite their chemical heterogeneity, all NSAIDs share the
      similar therapeutic property of inhibiting the cyclo-oxygenase enzyme. The appeal
      of using NSAIDs in the treatment of ocular inflammation hinges on the
      complications associated with corticosteroids, the other commonly used therapy
      for ophthalmic inflammation.

PMID- 17547473
TI  - Dihydropyridine calcium channel antagonists in the management of hypertension.
AB  - Dihydropyridine calcium channel antagonists have been maligned in recent years
      because of concerns regarding their cardiovascular and overall safety profile.
      Specifically, it was widely publicised in the mid-1990s that these agents might
      increase the risk of myocardial infarction, gastrointestinal bleeding and cancer.
      Data linking these agents with increased cardiovascular risk were based on
      nonrandomised studies and implicated short-acting, immediate-release agents.
      These results were inappropriately extrapolated to longer-acting compounds,
      extended-release products, and to the non-dihydropyridine class. Fortunately,
      recent studies have vindicated the class from safety allegations. These studies
      are reviewed herein. Compared with both diuretics and contemporary agents,
      amlodipine decreases cardiovascular events to a similar or greater extent without
      evidence for increased coronary heart disease, gastrointestinal bleeding or
      cancer. Despite these data, initial concerns have had lasting repercussions, as
      the use of dihydropyridine calcium channel antagonists appears to lag behind what
      emerging data would support. Dihydropyridine calcium channel antagonists have
      several noteworthy attributes that merit consideration in the management of
      hypertension. The blood pressure response to this class of drugs is less
      contingent on patient factors such as age and race compared with other
      antihypertensive agents (e.g. ACE inhibitors). Dihydropyridine calcium channel
      antagonists may exert effects that protect against stroke that are independent of
      their blood pressure-lowering mechanism. Unlike diuretics and beta-adrenoceptor
      anatagonists (beta-blockers), dihydropyridine calcium channel antagonists are
      lipid neutral and do not disturb glucose homeostasis. Dihydropyridine calcium
      channel antagonists demonstrate a highly desirable profile when administered as
      part of combination therapy. Combinations of dihydropyridine calcium channel
      antagonists and ACE inhibitors or angiotensin receptor antagonists display
      additive efficacy and an enviable adverse-effect profile. Collectively, the
      cardiovascular benefit, metabolic neutrality and homogeneous blood pressure
      response illuminated in recent studies, and reviewed here, represent a
      reaffirmation of the benefit of long-acting dihydropyridine calcium channel
      antagonists and should serve to help reinforce the critical importance of these
      agents in the therapeutic armamentarium against cardiovascular disease.

PMID- 17547474
TI  - HER2-positive breast cancer: current and future treatment strategies.
AB  - In the year 2006, breast cancer was estimated to affect >200,000 American women
      and cause nearly 56,000 deaths. Furthermore, breast cancer is the most common
      cancer diagnosed and second most common cause of cancer-related deaths in women.
      The current treatment armamentarium for breast cancer includes chemotherapy,
      endocrine therapy and biological therapy. Treatment has become more
      individualised based on characteristics of the tumour including overexpression of
      the human epidermal growth factor receptor (HER)-2. Between 20 and 30% of all
      breast cancers overexpress HER2, which means 40,000 - 60,000 patients will have
      this type of cancer.Previously, overexpression of HER2 was a negative prognostic
      and predictive risk factor for survival; however, with the advent of trastuzumab,
      patients' prognosis is improving in all treatment settings. Much controversy
      exists in the use of trastuzumab, including (i) the sequence of adjuvant
      trastuzumab (concurrent with chemotherapy or sequential); (ii) the treatment
      duration (<1 year, 1 year or 2 years); and (iii) the treatment choice upon
      disease progression (whether to continue or not with trastuzumab and add another
      cytotoxic agent). Current trials are ongoing to help answer these
      questions.Furthermore, there has been interest in predicting which HER2-positive
      patients would require anthracycline therapy, and which could avoid anthracycline
      therapy and its toxicities. Novel therapeutics, such as lapatinib, an oral
      tyrosine kinase inhibitor, which blocks both the epidermal growth factor receptor
      and HER2 receptor has recently been approved by the US FDA. Whereas pertuzumab, a
      humanised monoclonal antibody, directed against heterodimerisation of HER2 and
      HER3 has entered phase II and III clinical trials.

PMID- 17547475
TI  - Hyoscine butylbromide: a review of its use in the treatment of abdominal cramping
      and pain.
AB  - Abdominal cramping and pain is a frequent problem in the adult population of
      Western countries, with an estimated prevalence of < or =30%. Hyoscine
      butylbromide (scopolamine butylbromide) [Buscopan/Buscapina] is an antispasmodic
      drug indicated for the treatment of abdominal pain associated with cramps induced
      by gastrointestinal (GI) spasms. It was first registered in Germany in 1951 and
      marketed in 1952, and has since become available worldwide both as a prescription
      drug and as an over-the-counter medicine in many countries. This article reviews
      the pharmacology and pharmacokinetic profile of hyoscine butylbromide, and
      summarises efficacy and safety data from clinical trials of this drug for
      abdominal cramping and pain. Pharmacological studies have revealed that hyoscine
      butylbromide is an anticholinergic drug with high affinity for muscarinic
      receptors located on the smooth-muscle cells of the GI tract. Its anticholinergic
      action exerts a smooth-muscle relaxing/spasmolytic effect. Blockade of the
      muscarinic receptors in the GI tract is the basis for its use in the treatment of
      abdominal pain secondary to cramping. Hyoscine butylbromide also binds to
      nicotinic receptors, which induces a ganglion-blocking effect. Several
      pharmacokinetic studies in humans have consistently demonstrated the low systemic
      availability of hyoscine butylbromide after oral administration, with plasma
      concentrations of the drug generally being below the limit of quantitation. The
      bioavailability of hyoscine butylbromide, estimated from renal excretion, was
      generally <1%. However, because of its high tissue affinity for muscarinic
      receptors, hyoscine butylbromide remains available at the site of action in the
      intestine and exerts a local spasmolytic effect.Ten placebo-controlled studies
      have evaluated the efficacy and safety of oral or rectal hyoscine butylbromide.
      Hyoscine butylbromide was considered beneficial in all of these trials, which
      supports its use in the treatment of abdominal pain caused by cramping. Hyoscine
      butylbromide is barely absorbed and detectable in the blood and does not
      penetrate the blood-brain barrier, and is, therefore, generally well tolerated.
      Few adverse events have been reported; in particular, no significant increases in
      the incidence of anticholinergic-related adverse effects have been observed. In
      summary, hyoscine butylbromide appears to be a valuable treatment option for
      patients with symptoms of abdominal pain or discomfort associated with cramping.

PMID- 17547476
TI  - Imidapril: a review of its use in essential hypertension, Type 1 diabetic
      nephropathy and chronic heart failure.
AB  - Imidapril (Tanatril), through its active metabolite imidaprilat, acts as an ACE
      inhibitor to suppress the conversion of angiotensin I to angiotensin II and
      thereby reduce total peripheral resistance and systemic blood pressure (BP). In
      clinical trials, oral imidapril was an effective antihypertensive agent in the
      treatment of mild to moderate essential hypertension. Some evidence suggests that
      imidapril also improves exercise capacity in patients with chronic heart failure
      (CHF) and reduces urinary albumin excretion rate in patients with type 1 diabetes
      mellitus. Imidapril was well tolerated, with a lower incidence of dry cough than
      enalapril or benazepril, and is a first choice ACE inhibitor for the treatment of
      mild to moderate essential hypertension.

PMID- 17547477
TI  - Imidapril: will fewer adverse events translate into better long-term outcomes?

PMID- 17547478
TI  - Cognitive behavioral therapy in the elderly: what every PCP should know about
      CBT.

PMID- 17547479
TI  - Contact dermatitis: diagnosing and treating skin conditions in the elderly.
AB  - Contact dermatitis is a significant cause of skin disease in geriatric patients.
      We discuss factors that predispose older adults to contact dermatitis, such as
      changes in barrier function and types of commonly contacted irritants and
      allergens.

PMID- 17547480
TI  - Use of cognitive behavioral therapy in late-life psychiatric disorders.
AB  - With prevalence rates approaching 10% for anxiety disorders and 6% for major
      depression, anxiety and depression have a significant impact on adults in later
      life. Cognitive behavioral therapy (CBT) is a psychosocial intervention for
      anxiety and depression that can serve as a useful alternative or adjunct to
      pharmacologic intervention for older adults.

PMID- 17547481
TI  - Itchy lesion on the forehead.

PMID- 17547482
TI  - (Close) distance makes the heart grow fonder:Improving implicit racial attitudes
      and interracial interactions through approach behaviors.
AB  - In 4 studies, the authors examined the effect of approaching Blacks on implicit
      racial attitudes and immediacy behaviors. In Studies 1-3, participants were
      trained to pull a joystick toward themselves or to push it away from themselves
      when presented with photographs of Blacks, Whites, or Asians before completing an
      Implicit Association Test to measure racial bias. In Study 4, the effect of this
      training procedure on nonverbal behavior in an interracial contact situation was
      investigated. Results from the studies demonstrated that approaching Blacks
      decreased participants' implicit racial prejudice and increased immediacy when
      interacting with a Black confederate. The implications of these findings for
      current theories on approach, avoidance, and intergroup relations are discussed.

PMID- 17547483
TI  - Error and bias in comparative judgment: on being both better and worse than we
      think we are.
AB  - People believe that they are better than others on easy tasks and worse than
      others on difficult tasks. In previous attempts to explain these better-than
      average and worse-than-average effects, researchers have invoked bias and
      motivation as causes. In this article, the authors develop a more parsimonious
      account, the differential information explanation, in which it is assumed only
      that people typically have better information about themselves than they do about
      others. When one's own performance is exceptional (either good or bad), it is
      often reasonable to assume others' will be less so. Consequently, people estimate
      the performance of others as less extreme (more regressive) than their own. The
      result is that people believe they are above average on easy tasks and below
      average on difficult tasks. These effects are exacerbated when people have
      accurate information about their performances, increasing the natural discrepancy
      between knowledge of the self and knowledge of others. The effects are attenuated
      when people obtain accurate information about the performances of others.

PMID- 17547484
TI  - Misunderstanding the affective consequences of everyday social interactions: the
      hidden benefits of putting one's best face forward.
AB  - Positive self-presentation may have beneficial consequences for mood that are
      typically overlooked. Across a series of studies, participants underestimated how
      good they would feel in situations that required them to put their best face
      forward. In Studies 1 and 2A, participants underestimated the emotional benefits
      of interacting with an opposite sex stranger versus the benefits of interacting
      with a romantic partner. In Study 2B, participants who were instructed to engage
      in self-presentation felt happier after interacting with their romantic partner
      than participants who were not given this instruction, although other
      participants serving as forecasters did not anticipate such benefits. Increasing
      the generalizability of this self-presentation effect across contexts, the
      authors demonstrated that participants also underestimated how good they would
      feel before and after being evaluated by another person (Studies 3 and 4). This
      failure to recognize the affective benefits of putting one's best face forward
      may underlie forecasting errors regarding the emotional consequences of the most
      common forms of social interactions.

PMID- 17547485
TI  - Across the thin blue line: police officers and racial bias in the decision to
      shoot.
AB  - Police officers were compared with community members in terms of the speed and
      accuracy with which they made simulated decisions to shoot (or not shoot) Black
      and White targets. Both samples exhibited robust racial bias in response speed.
      Officers outperformed community members on a number of measures, including
      overall speed and accuracy. Moreover, although community respondents set the
      decision criterion lower for Black targets than for White targets (indicating
      bias), police officers did not. The authors suggest that training may not affect
      the speed with which stereotype-incongruent targets are processed but that it
      does affect the ultimate decision (particularly the placement of the decision
      criterion). Findings from a study in which a college sample received training
      support this conclusion.

PMID- 17547486
TI  - Social acceptance and self-esteem: tuning the sociometer to interpersonal value.
AB  - The authors draw on sociometer theory to propose that self-esteem is attuned to
      traits that garner others' acceptance, and the traits that garner acceptance
      depend on one's social role. Attunement of self-esteem refers to the linkage, or
      connection, between self-esteem and specific traits, which may be observed most
      clearly in the association between self-esteem and specific self-evaluations. In
      most roles, appearance and popularity determine acceptance, so self-esteem is
      most attuned to those traits. At the same time, interdependent social roles
      emphasize the value of communal qualities, so occupants of those roles have self
      esteem that is more attuned to communal qualities than is the general norm. To
      avoid the biases of people's personal theories, the authors assessed attunement
      of self-esteem to particular traits indirectly via the correlation between self
      esteem and self-ratings, cognitive accessibility measures, and an experiment
      involving social decision making. As hypothesized, self-esteem was generally more
      attuned to appearances than to communal qualities, but interdependent social
      roles predicted heightened attunement of self-esteem to qualities like kindness
      and understanding.

PMID- 17547487
TI  - The socialization of dominance: peer group contextual effects on homophobic and
      dominance attitudes.
AB  - Using the framework of social dominance theory, the current investigation tested
      for the contextual effects of adolescent peer groups on individuals' homophobic
      and social dominance attitudes. Results from multilevel models indicated that
      significant differences existed across peer groups on homophobic attitudes. In
      addition, these differences were accounted for on the basis of the hierarchy
      enhancing or -attenuating climate of the group. A group socialization effect on
      individuals' social dominance attitudes over time was also observed. Furthermore,
      the social climate of the peer group moderated the stability of individuals'
      social dominance attitudes. Findings support the need to examine more proximal
      and informal group affiliations and earlier developmental periods in efforts to
      build more comprehensive theoretical models explaining when and how prejudiced
      and dominance attitudes are formed and the way in which they are perpetuated.

PMID- 17547488
TI  - No pain, no gain: the conditions under which upward comparisons lead to better
      performance.
AB  - In 3 studies, the authors explored the relation between threatening upward social
      comparisons and performance. In an initial study, participants were exposed to
      comparison targets who either threatened or boosted self-evaluations and then
      completed a performance task. Participants exposed to the threatening target
      performed better than those in a control group, whereas those exposed to the
      nonthreatening target performed worse. In Study 2, self-affirmation prior to
      comparison with threatening targets eliminated performance improvements. In Study
      3, performance improvements were found only when the performance domain was
      different from the domain of success of the comparison target. These boundary
      conditions suggest that increases in performance following social comparison
      arise from individuals' motivations to maintain and repair self-evaluations.
      Implications for the study of the behavioral consequences of social comparison
      are discussed.

PMID- 17547489
TI  - Perceived discrimination as worldview threat or worldview confirmation:
      implications for self-esteem.
AB  - In 3 studies, the authors tested the hypothesis that discrimination targets'
      worldview moderates the impact of perceived discrimination on self-esteem among
      devalued groups. In Study 1, perceiving discrimination against the ingroup was
      negatively associated with self-esteem among Latino Americans who endorsed a
      meritocracy worldview (e.g., believed that individuals of any group can get ahead
      in America and that success stems from hard work) but was positively associated
      with self-esteem among those who rejected this worldview. Study 2 showed that
      exposure to discrimination against their ingroup (vs. a non-self-relevant group)
      led to lower self-esteem, greater feelings of personal vulnerability, and ingroup
      blame among Latino Americans who endorsed a meritocracy worldview but to higher
      self-esteem and decreased ingroup blame among Latino Americans who rejected it.
      Study 3 showed that compared with women informed that prejudice against their
      ingroup is pervasive, women informed that prejudice against their ingroup is rare
      had higher self-esteem if they endorsed a meritocracy worldview but lower self
      esteem if they rejected this worldview. Findings support the idea that perceiving
      discrimination against one's ingroup threatens the worldview of individuals who
      believe that status in society is earned but confirms the worldview of
      individuals who do not.

PMID- 17547490
TI  - Grit: perseverance and passion for long-term goals.
AB  - The importance of intellectual talent to achievement in all professional domains
      is well established, but less is known about other individual differences that
      predict success. The authors tested the importance of 1 noncognitive trait: grit.
      Defined as perseverance and passion for long-term goals, grit accounted for an
      average of 4% of the variance in success outcomes, including educational
      attainment among 2 samples of adults (N=1,545 and N=690), grade point average
      among Ivy League undergraduates (N=138), retention in 2 classes of United States
      Military Academy, West Point, cadets (N=1,218 and N=1,308), and ranking in the
      National Spelling Bee (N=175). Grit did not relate positively to IQ but was
      highly correlated with Big Five Conscientiousness. Grit nonetheless demonstrated
      incremental predictive validity of success measures over and beyond IQ and
      conscientiousness. Collectively, these findings suggest that the achievement of
      difficult goals entails not only talent but also the sustained and focused
      application of talent over time.

PMID- 17547491
TI  - Influence and adjustment goals: sources of cultural differences in ideal affect.
AB  - Previous studies have found that in American culture high-arousal positive states
      (HAP) such as excitement are valued more and low-arousal positive states (LAP)
      such as calm are valued less than they are in Chinese culture. What specific
      factors account for these differences? The authors predicted that when people and
      cultures aimed to influence others (i.e., assert personal needs and change
      others' behaviors to meet those needs), they would value HAP more and LAP less
      than when they aimed to adjust to others (i.e., suppress personal needs and
      change their own behaviors to meet others' needs). They test these predictions in
      1 survey and 3 experimental studies. The findings suggest that within and across
      American and Chinese contexts, differences in ideal affect are due to specific
      interpersonal goals.

PMID- 17547492
TI  - Culture, gender, and the self: variations and impact of social comparison
      processes.
AB  - Psychological differences between women and men, far from being invariant as a
      biological explanation would suggest, fluctuate in magnitude across cultures.
      Moreover, contrary to the implications of some theoretical perspectives, gender
      differences in personality, values, and emotions are not smaller, but larger, in
      American and European cultures, in which greater progress has been made toward
      gender equality. This research on gender differences in self-construals involving
      950 participants from 5 nations/cultures (France, Belgium, the Netherlands, the
      United States, and Malaysia) illustrates how variations in social comparison
      processes across cultures can explain why gender differences are stronger in
      Western cultures. Gender differences in the self are a product of self
      stereotyping, which occurs when between-gender social comparisons are made. These
      social comparisons are more likely, and exert a greater impact, in Western
      nations. Both correlational and experimental evidence supports this explanation.

PMID- 17547493
TI  - A required rural health module increases students' interest in rural health
      careers.
AB  - INTRODUCTION: The Australian Commonwealth Department of Health and Ageing has
      funded University Departments of Rural Health (UDRHs) to facilitate student
      placements with the goal of encouraging students to choose rural health practice.
      The objective of this article is twofold: first, to report student feedback
      regarding The University of Melbourne-UDRH required 4 week Rural Health Module
      based in Shepparton, Victoria, at the School of Rural Health, with placements in
      communities in rural northeast Victoria; and second, to identify students'
      attitudes about practising in rural areas at the completion of the course.
      METHODS: Student evaluations conducted at the completion of the program were
      analysed utilising both quantitative and qualitative survey questions. RESULTS:
      Of 393 students who completed the course, 93% participated in the evaluation.
      Over half (70%) said that the course increased their interest in rural health
      issues more than 'somewhat', and 47% stated that the course increased their
      interest in practising rurally more than 'somewhat'. Students valued their
      community placements highly but wanted greater clinical focus. CONCLUSIONS: A
      required community-based rural health course positively influences many medical
      students' reported intention toward rural practice and increases most students
      interest in rural health. Rural general practice placements are in short supply.
      This course offers valuable rural experience to students without depending
      significantly on GPs, but student feedback has increased efforts to make the
      course more clinically focussed.

PMID- 17547495
TI  - Toll-like receptor signaling in HIV-1 infection: a potential target for therapy?

PMID- 17547496
TI  - Optimizing sputum smear microscopy for the diagnosis of pulmonary tuberculosis.

PMID- 17547497
TI  - Combating the growing problem of methicillin-resistant Staphylococcus aureus: do
      the newer antibiotics represent a better alternative to vancomycin?

PMID- 17547500
TI  - Tinidazole for bacterial vaginosis.
AB  - Tinidazole has been used for bacterial vaginosis (BV) outside the USA for almost
      four decades. Tinidazole has recently been resurrected and FDA approved for
      trichomoniasis and BV in the USA and is being restudied as an alternative to
      metronidazole for BV. In vitro antimicrobial activity and pharmacokinetics
      studies indicate that when compared directly with metronidazole, tinidazole has
      minor but possibly relevant antimicrobial as well as pharmacokinetic advantages.
      Clinical comparisons have been infrequent, although the limited head-to-head
      studies indicate minimal therapeutic advantage with tinidazole. Perhaps the more
      relevant differences relate to the enhanced tolerance and reduced toxicity of
      tinidazole. Currently, studies are still ongoing directly comparing the clinical
      efficacy of metronidazole and tinidazole. These studies should establish the role
      of tinidazole in the treatment of BV; however, cure rates are unlikely to be
      significantly different.

PMID- 17547501
TI  - Fosamprenavir calcium plus ritonavir for HIV infection.
AB  - Fosamprenavir is a protease inhibitor (PI) approved for the treatment of HIV-1
      infection. Fosamprenavir is a prodrug of amprenavir developed to reduce the pill
      burden yet maintain the unique resistance pattern and efficacy associated with
      amprenavir. In a head-to-head, noninferiority trial in antiretroviral treatment
      naive HIV-infected patients, the antiviral efficacy and tolerability of ritonavir
      boosted fosamprenavir was not inferior to ritonavir-boosted lopinavir, when the
      PIs were combined with two other nucleoside reverse transcriptase inhibitors.
      There are fewer studies published about fosamprenavir use in antiretroviral
      treatment-experienced HIV-infected patients. The high genetic barrier to the
      development of resistance to fosamprenavir and the low level of cross-resistance
      between ritonavir-boosted fosamprenavir and other PI regimens are notable. As
      with amprenavir, gastrointestinal disturbance and rash are the most frequent
      short-term treatment-limiting events with fosamprenavir. Treatment with ritonavir
      boosted fosamprenavir can produce a durable response. To date, fosamprenavir is
      one of the recommended preferred PI components for the treatment of
      antiretroviral-naive HIV-infected patients.

PMID- 17547502
TI  - Piperacillin-tazobactam: a beta-lactam/beta-lactamase inhibitor combination.
AB  - Piperacillin-tazobactam is a beta-lactam/beta-lactamase inhibitor combination
      with a broad spectrum of antibacterial activity that includes Gram-positive and 
      negative aerobic and anaerobic bacteria. Piperacillin-tazobactam retains its in
      vitro activity against broad-spectrum beta-lactamase-producing and some extended
      spectrum beta-lactamase-producing Enterobacteriaceae, but not against isolates of
      Gram-negative bacilli harboring AmpC beta-lactamases. Piperacillin-tazobactam has
      recently been reformulated to include ethylenediaminetetraacetic acid and sodium
      citrate; this new formulation has been shown to be compatible in vitro with the
      two aminoglycosides, gentamicin and amikacin, allowing for simultaneous Y-site
      infusion, but not with tobramycin. Multicenter, randomized, double-blinded
      clinical trials have demonstrated piperacillin-tazobactam to be as clinically
      effective as relevant comparator antibiotics. Clinical trials have demonstrated
      piperacillin-tazobactam to be effective for the treatment of patients with intra
      abdominal infections, skin and soft tissue infections, lower respiratory tract
      infections, complicated urinary tract infections, gynecological infections and
      more recently, febrile neutropenia. Piperacillin-tazobactam has an excellent
      safety and tolerability profile and continues to be a reliable option for the
      empiric treatment of moderate-to-severe infections in hospitalized patients.

PMID- 17547503
TI  - Lethal interaction: the colliding epidemics of tobacco and tuberculosis.
AB  - Tobacco consumption ranks high among the leading health risks and tuberculosis
      (TB) is a major public health issue in countries where the smoking problem has
      reached epidemic proportions. Given that both smoking and TB are major health
      concerns and are widely prevalent in several countries, it is surprising that the
      association between smoking and TB is still a matter of debate and controversy.
      Although several studies have evaluated the effect of smoking on TB, the
      association has been largely overlooked by the TB and public health communities
      at large. Three recent reviews, including two meta-analyses, have summarized a
      large body of published literature on the association between smoking and various
      TB outcomes. These reviews show that there is considerable evidence that tobacco
      smoking is associated with TB. The evidence is strong for TB disease but less
      strong for TB infection and mortality. Even if the effect is relatively modest,
      the population-attributable risk is likely to be substantial due to the
      widespread nature of tobacco exposure. TB control programs must begin to address
      tobacco control as a potential preventive intervention. Since tobacco control
      will have multiple health benefits, it is likely to be a highly cost-effective
      intervention from a societal perspective.

PMID- 17547504
TI  - Vancomycin: does it still have a role as an antistaphylococcal agent?
AB  - The recognition of the shortcomings of vancomycin as an antistaphylococcal agent,
      together with the burgeoning availability of alternative effective
      antistaphylococcal antibiotics, has led to a reassessment of the role of this
      glycopeptide antimicrobial in clinical therapeutics. Evidence indicates that
      vancomycin is inferior to semisynthetic penicillins in the treatment of
      infections due to methicillin-susceptible Staphylococcus aureus. Additional
      evidence suggests that vancomycin may be inferior to some comparator agents in
      the treatment of infections due to methicillin-resistant S. aureus (MRSA). While
      high-level resistance remains rare, data from some centers suggest an
      evolutionary change in S. aureus, evidenced by reduced susceptibility to
      vancomycin. This, together with the problem of heteroresistance to vancomycin, as
      well as poor tissue penetration after its systemic administration, presents
      potential obstacles to the successful therapy of S. aureus infections with this
      glycopeptide. While it has been suggested that these problems may be overcome by
      administration of vancomycin in much higher doses, the efficacy and safety of
      this approach remains to be determined and will require randomized clinical
      trials for its demonstration. A number of novel agents with activity against MRSA
      have been introduced to clinical practice in the last 2 years and others are
      still in the investigational stage. Despite the fact that these newer agents have
      been compared with vancomycin in trials only designed to demonstrate
      noninferiority, some potential evidence of superiority over vancomycin has
      emerged. While the relative roles of each of these newer agents and vancomycin
      can only be determined definitively by performance of adequately powered
      randomized clinical trials, current evidence suggests that vancomycin may be an
      inferior therapeutic agent.

PMID- 17547505
TI  - Advanced therapeutic and prophylactic strategies for Epstein-Barr virus infection
      in immunocompromised patients.
AB  - Epstein-Barr virus (EBV) is an ubiquitous human herpesvirus. Primary infection is
      generally subclinical but in certain circumstances, such as in patients with
      either hereditary or secondary immunodeficiency, EBV infection may cause overt
      disease that is often lethal. Strategies for the prophylaxis and treatment of
      these potentially life-threatening complications of EBV infection have advanced
      dramatically. They include immunological-based approaches targeted at EBV
      infected cells, as well as improvement in the treatment of the underlying and
      predisposing disease. This review will discuss EBV biology and immune events that
      occur in both immunocompetent and immunocompromised individuals and introduce the
      novel prophylactic and therapeutic strategies for EBV-associated life-threatening
      diseases.

PMID- 17547506
TI  - Chemokines and their receptors in respiratory disease: a therapeutic target for
      respiratory syncytial virus infection.
AB  - Cell recruitment is a multistep process orchestrated by chemokines and their
      receptors. The chemokine/receptor system is central to many inflammatory
      diseases, making it a key target for therapeutic intervention. Despite complexity
      and redundancy within the system, effective antagonists are in development and
      undergoing clinical trials, for example, maraviroc, for use in HIV treatment.
      Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract
      infection in infants, with global annual infection estimated at 64 million
      people. Current treatment is purely supportive, with no effective vaccine
      available. RSV pathology is partly due to excessive airway inflammation. Evidence
      is growing for a key role for chemokine receptors. Receptor blockade may
      therefore provide a feasible therapeutic option to inhibit RSV-induced
      inflammation and thereby reduce disease severity.

PMID- 17547507
TI  - Recent developments in human cytomegalovirus diagnosis.
AB  - Since the early 1990s, great efforts have been made in the field of human
      cytomegalovirus (HCMV) diagnosis. Besides HCMV diagnosis in immunosuppressed
      patients (solid organ transplant recipients, hematopoietic stem cell transplant
      patients and AIDS patients), diagnosis in connection with congenital HCMV
      infection is of great interest. This review focuses on the development and
      clinical utility of serological assays, as well as on virological tests
      (molecular and nonmolecular assays). Interpretation of these tests is strongly
      dependent on the patient group (solid organ transplant recipients and
      hematopoietic stem cell transplant patients) and whether the tests are used for
      screening, risk stratification or diagnosis. Furthermore, a better understanding
      of HCMV infection has led to new approaches in HCMV diagnosis and monitoring.
      Thus, assays for viral resistance testing and assays for monitoring the HCMV
      specific cellular immune response are increasingly important for the guidance of
      antiviral therapy.

PMID- 17547508
TI  - Treatment of congenital cytomegalovirus: where are we now?
AB  - Congenital cytomegalovirus (CMV) is the most common congenital infection in the
      USA, affecting approximately 1% of all live births. While the majority of infants
      will remain asymptomatic, approximately 10% will be symptomatic at birth and
      another 10-15% will go on to develop problems during the first 6 years of life.
      Congenital CMV is now the most common cause of nonhereditary sensorineural
      hearing loss in children. Accordingly, researchers and clinicians have long been
      interested in identifying strategies to prevent or treat symptomatic congenital
      CMV infection. This article reviews congenital CMV with a focus on treatment
      strategies.

PMID- 17547509
TI  - Vaccine strategies against human cytomegalovirus infection.
AB  - Human cytomegalovirus (HCMV) disease is a major cause of morbidity and mortality
      in neonates and immunocompromised populations, such as transplant recipients and
      HIV-infected patients. The development of a vaccine to prevent HCMV infection or
      disease has been assigned the highest priority by the US Institute of Medicine.
      Although, after 30 years of intensive study, a clinically licensed vaccine is
      still not available, significant progress has been made in the field of HCMV
      vaccine development, along with greater understanding of HCMV immunology,
      molecular biology and pathology. In recent years, new vaccine strategies have
      been developed that have shown promising results in preclinical studies and are
      able to induce HCMV-specific immune responses in clinical studies, although
      efficacy data are not yet available. Here we review the history of HCMV vaccine
      development and the current strategies in the development of new HCMV vaccines.
      We propose that research should focus on the development of a vaccine to prevent
      or control HCMV-related disease rather than to prevent infection, and that
      discerning strategies should be used for targeting HCMV disease in different
      clinical settings.

PMID- 17547510
TI  - Immunological options for the treatment of tuberculosis: evaluation of novel
      therapeutic approaches.
AB  - The emergence of multidrug-resistant tuberculosis strains and the coinfection
      with HIV, together with advances in immunology, have led to renewed interest
      regarding ways to exploit the immune responses against Mycobacterium tuberculosis
      therapeutically. Here we review the fundamentals of tuberculosis therapy in view
      of the epidemiological and clinical challenges, and explore the experience with
      immune-based therapies for the treatment of active tuberculosis. These immune
      based therapies are discussed here with the aim of assessing their potential use
      as adjuncts to chemotherapy.

PMID- 17547511
TI  - Chronic helminth infections may negatively influence immunity against
      tuberculosis and other diseases of public health importance.
AB  - Tuberculosis (TB) has once again become a major public health threat owing to the
      combined effects of deteriorating socioeconomic situations and the emergence of
      the HIV/AIDS pandemic. The only vaccine available against TB, although effective
      in reducing the burden of childhood TB, shows enormous variability in its
      efficacy against pulmonary TB, which is the most common form of the disease in
      adults. Most areas of high TB incidence and poor TB vaccine efficacy have a high
      prevalence of intestinal helminth infections. Such infections have been shown to
      cause a range of immunomodulation characterized by enhanced T helper 2-type
      cytokine profile, high immunoglobulin E levels and upregulated regulatory T-cell
      activity, as well as chronic immune activation. An altered background immune
      profile could have adverse effects on the outcome of subsequent infections and
      vaccinations. In support of this hypothesis, studies conducted in animals and
      humans living in worm-endemic areas have shown that helminths impair resistance
      against a number of infections of major public health importance, including TB,
      malaria and HIV/AIDS. Understanding such interactions could assist in the design
      of vaccines against these diseases.

PMID- 17547512
TI  - Advances in malaria diagnosis.
AB  - Malaria is a leading cause of mortality worldwide and accurate diagnostic testing
      for malaria can potentially save an estimated 100,000 lives annually. New
      technologies have the potential to circumvent limitations of the traditional
      diagnostic method, light microscopy, which is labor intensive and requires
      considerable technician expertise. Immunochromatographic tests, which are easy to
      use in field conditions and relatively inexpensive, offer a potential solution to
      the problem of malaria overtreatment in resource-poor endemic countries. Assays
      based on the PCR are highly sensitive, can be used for unambiguous species
      identification and, thus, may increasingly complement or even replace light
      microscopy in developed countries. Experimental diagnostics using flow cytometry
      and mass spectrometry are currently under investigation for high-throughput
      screening.

PMID- 17547513
TI  - Tea catechins as a potential alternative anti-infectious agent.
AB  - Besides well-known health benefits, green tea catechins exert antimicrobial and
      antiviral activities against a variety of infectious agents. Although the
      detailed mechanism of the antimicrobial activity of tea catechins remains to be
      explored, the broad-spectrum activity of catechins may involve common target(s),
      such as the cell membrane, in addition to specific targets for each pathogen.
      This extends to antiviral activities, where many pronounced activities were
      reported for enveloped viruses. Yet, the effectiveness of tea catechins as
      antimicrobials is compromised by relative chemical instability and poor
      bioavailability. Whether tea catechins will emerge as a viable option as
      alternative medicine or as a synergistic combination therapy with pre-existing
      antivirals or antibiotics must therefore depend on a method of delivery that
      ensures its stability and bioavailability. However, green tea may provide an
      option for mitigating the health and economic burdens associated with emerging
      and re-emerging infectious diseases, especially considering the paucity of
      effective control measures. Considering the zoonotic nature of newly arising
      infectious diseases, the dual use of green tea components in both humans and
      livestock may reduce animal-human transmission, which would complement the
      current management of infectious diseases.

PMID- 17547514
TI  - Empiric therapy for febrile neutropenia: what are the choices?
AB  - The management of febrile neutropenia has evolved gradually over the years toward
      a risk-adapted strategy based on validated prediction rules by risk of
      complications. The drug choice for empiric therapy is influenced by several
      factors, either related to the patient or to the institution. Microbiological
      distribution of offending pathogens and their pattern of susceptibility to
      antibiotics are continuously changing. New mechanisms of resistance in both Gram
      negative and -positive bacteria have emerged. Guidelines and general statements
      should always be considered with the local epidemiology.

PMID- 17547515
TI  - In vitro and in vivo expression of human erythrocyte pyruvate kinase in erythroid
      cells: a gene therapy approach.
AB  - Human pyruvate kinase deficiency (PKD), an autosomal recessive disorder produced
      by mutations in the PKLR gene, is the most common cause of chronic nonspherocytic
      hemolytic anemia. Transduction of wild-type erythroid (R-type) pyruvate kinase
      (RPK) cDNA into deficient hematopoietic stem cells could be of potential use as
      rescue therapy in severe clinical cases. In this study, gammaretroviral vectors
      expressing human RPK were designed as possible gene therapy candidates for this
      disease. Through real-time quantitative reverse transcriptase-polymerase chain
      reaction, Western blotting, and flow cytometric analysis, we demonstrate stable
      RPK expression in both undifferentiated and differentiated murine erythroleukemia
      cells. In this in vitro assay, the proportion of transduced cells and the
      intensity of expression of the transgene remained unaltered after 6 months of
      culture. Moreover, transplanting human RPK-transduced Lin(-)Sca-1(+) mouse cells
      in myeloablated primary and secondary recipients rendered high proportions of
      erythroid precursors and mature erythrocytes expressing RPK, without inducing
      hematopoietic effects. These findings suggest that retroviral vectors could be
      useful for the delivery and expression of RPK in erythroid cells, and provide
      evidence of the potential use of gene therapy strategies to phenotypically
      correct erythroid PKD.

PMID- 17547516
TI  - Understanding racial differences in colorectal cancer aids in individualized
      medicine.

PMID- 17547518
TI  - Erlotinib: success of a molecularly targeted agent for the treatment of advanced
      pancreatic cancer.
AB  - Epidermal growth factor receptor (EGFR) is overexpressed by several solid tumors,
      including pancreatic cancer, and has become an important target for novel
      anticancer pharmacotherapy. Erlotinib (Tarceva, OSI-774) is an orally available
      small-molecule inhibitor of the EGFR tyrosine kinase. The addition of erlotinib
      to gemcitabine has been shown to prolong survival of patients treated for
      advanced pancreatic cancer in the National Cancer Institute of Canada PA.3 trial.
      This survival advantage is small yet noteworthy, in that numerous gemcitabine
      containing combinations have failed to show a statistically significant survival
      advantage over gemcitabine alone. The most frequent toxicities associated with
      the addition of erlotinib are diarrhea and rash. Erlotinib-induced rash appears
      to be predictive of outcome. Further clinical studies of erlotinib in the
      treatment of pancreatic cancer are ongoing.

PMID- 17547519
TI  - Iodine 131 tositumomab in the treatment of non-Hodgkin's lymphoma.
AB  - Iodine 131 (I131) tositumomab is composed of murine anti-CD20 antibody linked to
      the radioisotope I131. I131 tositumomab exploits the specificity of monoclonal
      antibody therapy and the radiosensitivity of non-Hodgkin's lymphoma to exact a
      combined antitumor effect. It is currently approved in the USA for treatment of
      relapsed or refractory low-grade (and transformed) non-Hodgkin's lymphoma. High
      response rates in this setting, with some patients achieving a remission of
      longer duration than that of their prior treatment, provided the basis for
      approval of the drug. Studies using I131 tositumomab as initial treatment for low
      grade non-Hodgkin's lymphoma (with or without chemotherapy), and in conditioning
      regimens for autologous transplantation, have yielded promising results.
      Randomized, comparative trials are needed to define its optimal clinical use.

PMID- 17547520
TI  - Oblimersen in the treatment of metastatic melanoma.
AB  - Oblimersen (Genasense is a Bcl-2 antisense compound that selectively targets Bcl
      2 RNA for degradation by RNase H and thereby decreases Bcl-2 protein production.
      Bcl-2 protein plays a major role in preventing apoptosis and has been linked to
      chemotherapy resistance in melanoma. Preclinical studies with oblimersen in
      melanoma cell lines and xenograft models of melanoma have demonstrated
      downregulation of Bcl-2 protein, induction of apoptosis and enhanced tumor
      response when combined with chemotherapy. Results of a Phase I/II study have
      shown that reducing Bcl-2 with oblimersen coincident with the administration of
      dacarbazine may amplify apoptosis and improve therapeutic outcome. A subsequent
      Phase III trial showed that the addition of oblimersen to dacarbazine
      significantly improved multiple clinical outcomes relative to dacarbazine alone
      based on an intent-to-treat analysis of progression-free survival and response
      rate (overall, complete and durable), as well as overall survival in patients
      with normal lactate dehydrogenase. This article reviews the biochemistry,
      pharmacodynamics and pharmacokinetics, safety and efficacy data related to
      oblimersen in melanoma.

PMID- 17547521
TI  - Endobronchial ultrasound-guided biopsy of coin lesions.
AB  - Evaluation of: Dooms CA, Verbeken EK, Becker HD, Demedts MG, Vansteenkiste JF:
      Endobronchial ultrasonography in bronchoscopic occult pulmonary lesions. J.
      Thorac. Oncol. 2, 121-124 (2007). Transbronchial biopsy (TBB) for solitary
      pulmonary nodules is usually performed under fluoroscopic guidance, but the
      diagnostic yield depends on lesion size and varies widely. An alternative
      guidance technique, endobronchial ultrasound (EBUS), also allows for the
      visualization of pulmonary nodules. Dooms and colleagues evaluated the yield of
      EBUS-guided TBB in a series of consecutive patients with a bronchoscopic-occult
      pulmonary lesion. The mean diameter of the lesions was 36.6 mm. A histologic
      diagnosis upon TBB was obtained in 84% of patients. However, the diagnostic yield
      was very poor for lesions less than 20 mm in diameter. The group concluded that
      EBUS-guided TBB is effective for localizing and diagnosing bronchoscopic-occult
      pulmonary masses.

PMID- 17547522
TI  - Setting the benchmark for tailoring treatment with EGFR tyrosine kinase
      inhibitors.
AB  - Overexpression and mutational activation of the epidermal growth factor receptor
      (EGFR) is involved in tumor development and progression in non-small-cell lung
      cancer (NSCLC). Somatic mutations in the EGFR kinase domain confer high
      sensitivity to tyrosine kinase inhibitors (TKIs). The two most frequent mutations
      are the exon 19 deletion and the exon 21 L858R. Distinct EGFR mutations differ in
      their effect on response and survival to TKIs. We have examined EGFR mutations in
      more than 1800 stage IV NSCLCs for erlotinib customization as both first- and
      second-line treatment. EGFR mutations cluster in never-smokers, women and
      adenocarcinomas, as has been described in multiple retrospective studies. The
      overall frequency of EGFR mutations in our study was 15% and the response in
      first- and second-line treatment was 84%. Overall, progression-free survival was
      13 months and median survival has not been reached. However, patients with exon
      19 deletions showed a significantly longer progression-free survival than those
      harboring L858R mutations. Despite abundant molecular evidence on the role of
      EGFR mutations, there is still no general agreement as to their predictive value.
      To clarify this important issue, the Spanish Lung Cancer Group has opened a Phase
      III trial comparing erlotinib with chemotherapy in stage IV NSCLC patients with
      EGFR mutations. This study is open to other European institutions.

PMID- 17547523
TI  - Evolving management of newly diagnosed brain metastases: expanding role of
      radiosurgery in lieu of whole brain radiation.
AB  - The use of stereotactic radiosurgery has grown increasingly prevalent in the
      management of patients with brain metastases. In this perspective we contend that
      a large number of patients can be offered the alternative of treatment with this
      modality alone, reserving whole brain radiation for salvage. The relevant data
      will be presented supporting this approach, with emphasis on the toxicities of
      whole brain radiation and equivalence of survival outcomes regardless of
      treatment approach. Patient selection for radiosurgery alone will also be
      addressed.

PMID- 17547524
TI  - Biomarker approaches to the development of cancer screening tests: can cancer
      blood tests become a routine health check-up?
AB  - Cancer is a deadly disease associated with high rates of morbidity and mortality.
      The vast majority of cancers are identified at a late stage, when therapy is
      rarely successful Morbidity and mortality associated with cancer can be reduced
      with improved prevention and early detection activities. Identification of cancer
      biomarkers is one of the most promising approaches for the detection of early
      stage malignant or even premalignant lesions with a simple blood test. A large
      number of research teams are investigating the role of biomarkers in cancer
      detection and progression, making the dream of early and painless cancer
      detection become a reality.

PMID- 17547525
TI  - Cancer vaccines: a promising cancer therapy against all odds.
AB  - Vaccination as an approach to control cancer growth and recurrence, also known as
      active-specific immunotherapy (ASI), has been successful at inducing immune
      responses, even in patients with advanced or metastatic disease. Clinical
      responses, as determined by the criteria set for chemotherapy and radiation, have
      been much more difficult to assess. In general, the effectiveness of ASI in
      advanced disease is expected to be limited. The lack of toxicity in thousands of
      vaccinated patients with many different tumor types, and clearly observed, albeit
      rare, efficacy, support the use of ASI in early disease following resection of
      the primary tumor or removal of precancerous lesions. This setting will permit a
      much more rational assessment of the long-term efficacy of ASI, as well as its
      toxicity. Given that ASI relies on a healthy immune system to be effective, it is
      also predicted to be more successful when it is employed prior to the use of
      standard chemotherapy. At the very least, it should be given primary
      consideration in situations where the role of cytotoxic chemotherapy is equivocal
      and patients are in need of a nontoxic alternative.

PMID- 17547526
TI  - Phytoestrogens: perpetrators or protectors?
AB  - Phytoestrogens are estrogen-like substances produced by plants that account for
      some of the constituents present in vegetation that may be responsible for the
      health benefits of a diet rich in fruit and vegetables. Phytoestrogens have a
      plethora of different actions that they are capable of exerting on cellular
      metabolism. This review will focus on some of the major non-estrogen receptor
      mediated cellular effects used by phytoestrogens and will draw attention to the
      fact that while they may have a number of beneficial effects, particularly in
      offering a protective effect against some hormone-dependent cancers, such as
      breast and prostate cancer, they may also have possible unfavorable effects by
      interfering with the functioning of normal cellular activities such as receptor
      mediated signal transduction and DNA replication, as well as being genotoxic,
      mutagenic and promoting the proliferation of some cancer cells.

PMID- 17547527
TI  - Cervical cancer screening following the implementation of prophylactic human
      papillomavirus vaccination.
AB  - The recognition that infection with certain human papillomavirus (HPV) types is a
      necessary cause of cervical cancer has opened new fronts in the prevention of
      this disease. Primary prevention is now possible via immunization with highly
      efficacious HPV vaccines, and secondary prevention has gained impetus with the
      advent of sensitive HPV-DNA testing to improve traditional Pap cytology screening
      programs. Although universal vaccination of teenagers and young women is a
      desirable policy, cost remains a key obstacle. To achieve cost-effective
      reductions in cervical cancer burden, prevention initiatives must consider
      screening and immunization as integrated and organized approaches that take
      advantage of HPV testing as a primary screening test followed by triage with Pap
      cytology. This strategy has the added benefit of providing immunosurveillance of
      vaccinated populations.

PMID- 17547528
TI  - Tumor hypoxia, DNA repair and prostate cancer progression: new targets and new
      therapies.
AB  - Increasingly, the tumor microenvironment and hypoxia are being studied as
      potential prognostic factors in prostate cancer given their effects on the
      hypoxia inducible factor-1alpha and vascular endothelial growth factor signaling
      pathways. Based on immunohistochemical studies using hypoxic cell markers and
      direct oxygen-electrode measurements, clinically relevant levels of hypoxia are
      detected in 30-90% of prostate cancers. Exciting new data suggest that hypoxia
      can alter cell-cycle checkpoints and DNA repair within the prostate epithelium,
      thereby driving genetic instability and tumor aggression. Novel therapies
      designed to target the hypoxic response and resulting defective DNA repair may
      therefore be effective as chemoprevention agents or as adjuncts to surgery,
      radiotherapy and chemotherapy to improve clinical outcome.

PMID- 17547529
TI  - Regional lymph node irradiation in breast cancer.
AB  - A recent meta-analysis, published by the Early Breast Cancer Trialists'
      Collaborative Group, demonstrated a clear survival advantage of post-operative
      radiotherapy on the breast, chest wall and regional lymphatics in node-positive
      disease. The extensive target volume in locoregional irradiation of breast
      cancer, in close proximity to the heart and lungs, complicates treatment
      planning. The breast or chest wall fields need to match the
      supraclavicular/axillary and parasternal fields, at the subclavicular and
      parasternal matchline, respectively. Dose distribution near the junction area is
      often inhomogeneous, and under- and over-dosage can occur, which can lead to
      recurrences and complications. This paper describes briefly the indications,
      complications and target localization concerning regional lymph node radiotherapy
      and discusses more extensively the advantages and disadvantages of the most
      frequently used treatment techniques.

PMID- 17547530
TI  - Aberrant kinase signaling: lessons from head and neck cancer.
AB  - Cancers, including head and neck squamous cell carcinoma (HNSCC), are
      characterized by the increased expression of receptor and nonreceptor tyrosine
      kinases. Many small molecules have been developed that selectively inhibit these
      kinases. These drugs have demonstrated antitumor effects in many preclinical
      cancer models and are now either approved for use in selected cancer patients or
      are under active clinical development. Receptor tyrosine kinases can also be
      targeted using monoclonal antibodies. Cetuximab is a chimeric antibody that
      inhibits the epidermal growth factor receptor and was approved for use in HNSCC,
      making it the first new drug for the treatment of this malignancy in over 40
      years. Serine/threonine kinases are also aberrantly expressed in HNSCC and
      inhibitors of these kinases are being developed for clinical use. These
      developments will allow for the rational design of treatment regimens for HNSCC
      patients based on the aberrant kinase signaling in their tumors.

PMID- 17547531
TI  - Cognition in organizations.
AB  - This article reviews major developments from 2000 to early 2007 in the
      psychological analysis of cognition in organizations. Our review, the first in
      this series to survey cognitive theory and research spanning the entire field of
      industrial and organizational psychology, considers theoretical, empirical, and
      methodological advances across 10 substantive domains of application. Two major
      traditions, the human factors and organizational traditions, have dominated
      cognitively oriented research in this field. Our central message is that the
      technological and human systems underpinning contemporary organizational forms
      are evolving in ways that demand greater cooperation among researchers across
      both traditions. Such cooperation is necessary in order to gain theoretical
      insights of sufficient depth and complexity to refine the explanation and
      prediction of behavior in organizations and derive psychologically sound
      solutions to the unprecedented information-processing burdens confronting the
      twenty-first century workforce.

PMID- 17547532
TI  - Histamine receptor H1 and dermatopontin: new downstream targets of the vitamin D
      receptor.
AB  - In this study, we used multipotential MSCs and microarray assays to follow the
      changing patterns of gene expression as MSCs were differentiated to osteoblasts.
      We analyzed co-expressed gene groups to identify new targets for known
      transcription factor VDR during differentiation. The roles of two genes
      (histamine receptor H1 and dermatopontin) as downstream targets for the VDR were
      confirmed by gel electromotility shift, siRNA inhibition, and chromatin
      immunoprecipitation assays. INTRODUCTION: Osteogenesis is stringently controlled
      by osteoblast-specific signaling proteins and transcription factors. Mesenchymal
      stem or multipotential stromal cells from bone marrow (MSCs) have been shown to
      differentiate into osteoblasts in the presence of vitamin D(3). MATERIALS AND
      METHODS: We used MSCs and microarray assays to follow the changing patterns of
      gene expression as MSCs were differentiated to osteoblasts. The data were
      analyzed with a previously developed strategy to identify new downstream targets
      of the vitamin D receptor (VDR), known osteogenesis transcription factor.
      Hierarchical clustering of the data identified 15 distinct patterns of gene
      expression. Three genes were selected that expressed in the same time-dependent
      pattern as osteocalcin, a known target for the VDR: histamine receptor H1 (HRH1),
      Spondin 2 (SPN), and dermatopontin (DPT). RT-PCR, electromotility shift, siRNA
      inhibition assays, and chromatin immunoprecipitation assays were used to analyze
      the role of VDR in activation of DPT and HRH1 during differentiation. RESULTS AND
      CONCLUSIONS: RT-PCR assays confirmed that the genes were expressed during
      differentiation of MSCs. The roles of two genes as downstream targets for the VDR
      were confirmed by gel electromotility shift and chromatin immunoprecipitation
      assays that showed the presence of VDR complex binding sequences. Overexpression
      of VDR in MG-63 osteosarcoma cells induced the expression of HRH1 and DPT.
      Inhibition studies with siRNA to DPT and HRH1 showed a decrease in MSC
      differentiation to osteogenic lineage. In addition, osteogenic differentiation of
      MSCs was inhibited by the HRH1 inhibitor mepyramine but not the HRH2 inhibitor
      ranitidine. In conclusion, we show that analysis of co-expressed gene groups is a
      good tool to identify new targets for known transcription factors.

PMID- 17547533
TI  - Zinc-finger transcription factor odd-skipped related 2 is one of the regulators
      in osteoblast proliferation and bone formation.
AB  - We report that Osr2 is one of the regulators of osteoblast function, because
      dominant-negative Osr2 transgenic mice exhibited decreased osteoblast activity
      and delayed mineralization in calvarial and tibial bone tissues. Our results
      indicate that Osr2 functions in regulation of osteoblast proliferation.
      INTRODUCTION: Molecular mechanisms that control bone formation have received
      attention with increasing knowledge related to genetic control of osteoblast
      differentiation. The odd-skipped related (Osr) gene is a zinc-finger
      transcription factor recently suggested to be involved in bone formation,
      although little is known about its role. MATERIALS AND METHODS: To elucidate the
      in vivo function of Osr2, we generated transgenic mice overexpressing dominant
      negative Osr2. RESULTS: In this study, N-terminal-deleted Osr2 was found to act
      as a dominant-negative mutant toward both Osr1 and Osr2. Dominant-negative Osr2
      (Osr2DeltaN) transgenic mice showed delayed mineralization in calvarial and
      cortical bone tissues. Furthermore, soft X-ray analysis of transgenic mice bones
      revealed distinctly increased radiolucency. Examinations of newborn Osr2DeltaN
      transgenic mice skeletons stained with alcian blue and alizarin red showed
      reduced intensities in the skull and skeletal elements. Morphologically,
      calvariae and tibias of Osr2DeltaN transgenic mice were composed of markedly
      thinner parietal and cortical bones and lower numbers of osteoblastic cells on
      bone surfaces, indicating a reduced proliferation of osteoblasts. Furthermore,
      calvarial osteoblasts obtained from Osr2DeltaN transgenic mice showed highly
      attenuated osteoblast differentiation and proliferation, confirming that Osr2 is
      needed for osteogenesis. Finally, results of Runx2-deficient cell assays
      suggested that Osr2 induces alkaline phosphatase (ALP) expression, but to a
      lesser degree than Runx2-expressing cells. CONCLUSIONS: Our genetic observations
      showed that the Osr2 gene plays a key role in osteoblastic cell proliferation.

PMID- 17547534
TI  - Strontium ranelate treatment improves trabecular and cortical intrinsic bone
      tissue quality, a determinant of bone strength.
AB  - Beside its influence on determinants of bone strength (geometry,
      microarchitecture), which is likely to be related to a cellular effect, strontium
      ranelate improves bone tissue quality as evaluated by nanoindentation, increasing
      elastic modulus, hardness, and dissipated energy in vertebrae of rats treated for
      104 wk with daily dose from 0 to 900 mg/kg. INTRODUCTION: We previously showed
      that strontium ranelate treatment improves the mechanical properties of the
      vertebral body and long bone midshaft in intact rats. The increased energy to
      failure obtained with strontium ranelate is essentially caused by an increase in
      plastic energy, suggesting that bone formed during treatment can withstand
      greater deformation before fracture. In the bone mineral phase, strontium is
      mainly located in the hydrated shell and could thus potentially influence
      intrinsic bone tissue quality. MATERIALS AND METHODS: To study whether strontium
      ranelate treatment could positively influence intrinsic bone tissue quality
      (elastic modulus, hardness, and dissipated energy), nanoindentation tests were
      performed at the level of trabecular nodes and cortex under physiological or dry
      conditions in vertebrae of rats treated for 104 wk with strontium ranelate at a
      daily dose of 0, 225, 450, or 900 mg/kg (n = 12 per group). Ex vivo microCT
      measurements and axial compression tests of adjacent vertebral bodies were also
      performed. Significance of difference was evaluated using ANOVA. RESULTS: In
      agreement with previous results, strontium ranelate (900 mg/kg/d) [corrected]
      increased versus controls in maximal load (+23%), total energy (+71%), and
      plastic energy (+143%). At the level of trabecular bone, strontium ranelate
      treatment resulted in a significant increase in elastic modulus (+15.1%, p <
      0.01), hardness (+11.5%, p < 0.05), and dissipated energy (+16.2%, p < 0.001)
      versus controls in physiological, but not in dry, conditions. The effect was less
      pronounced in cortex. CONCLUSIONS: These results show for the first time a direct
      action of strontium ranelate on bone tissue quality. Beside its shown influence
      on classical determinants of bone strength (geometry, microarchitecture), which
      is likely to be related to a cellular effect, strontium ranelate improves bone
      tissue quality. This could contribute to the increase in bone strength and thus
      be involved in the reduction of fracture risk in postmenopausal osteoporotic
      patients treated with strontium ranelate.

PMID- 17547535
TI  - Longitudinal analysis of mesenchymal progenitors and bone quality in the stem
      cell antigen-1-null osteoporotic mouse.
AB  - We performed a longitudinal analysis of bone quality in Sca-1-null mice. A tight
      temporal, site-specific association between Sca-1-deficient BMD deficiency and
      reduced mesenchymal progenitor frequency was observed. Defects in trabecular
      microarchitecture and mineralization were, at least partially, responsible for
      the age-related reduction in toughness of Sca-1(-/-) bones. INTRODUCTION: We
      previously showed that stem cell antigen 1 (Sca-1)-null mice undergo normal bone
      development but exhibit significantly decreased bone mass characteristic of age
      dependent osteoporosis. The objective of this study was to characterize the
      initiation and progression of the Sca-1 mutant skeletal phenotype at the
      cellular, structural, material, and mechanical levels. MATERIALS AND METHODS: Sca
      1-null and control mice were analyzed at 3, 5, 7, and 9 mo of age. In vitro
      osteoclastogenesis of bone marrow and spleen-derived progenitor populations was
      assessed. Bone marrow-derived mesenchymal progenitor frequency, along with
      osteogenic and adipogenic differentiation potential, was analyzed in vitro.
      Static histomorphometry of the sixth lumbar vertebrae was performed. Whole body,
      femoral, and vertebral BMD were assessed using DXA. Lumbar vertebrae were
      analyzed using microCT, back-scattered electron imaging, and compression tests.
      Three-point bending and femoral neck fracture tests were performed on excised
      femurs. RESULTS: Sca-1-null mice displayed an age-dependent, cell-autonomous
      osteoclast deficiency in vitro. From 7 mo of age onward, reduced Sca-1-null
      femoral BMD was observed alongside reduced mesenchymal progenitor frequency, and
      decreased in vitro osteogenic and adipogenic differentiation potential. Sca-1
      deficient mice exhibited reduced whole body BMD compared with controls at all
      time-points analyzed. Although no differences in spinal BMD were observed, Sca-1(
      /-) vertebrae exhibited decreased bone formation, with a maximal difference at 7
      mo of age, inferior trabecular microarchitecture, and a greater degree of
      mineralization. At all sites tested, Sca-1-null bones exhibited reduced energy to
      failure from 5 mo onward. CONCLUSIONS: We showed a tight association within Sca-1
      null mice between the initiation of stem cell defects and the exacerbation of
      deficiencies in bone quality at two sites clinically relevant to developing
      osteoporotic fractures. Sca-1-deficient mice, therefore, provide a novel and
      useful murine model of age-related osteoporosis, which with additional study,
      should further our understanding of the mechanisms underlying this increasingly
      prevalent disease.

PMID- 17547536
TI  - Heritability of BMD of femoral neck and lumbar spine: a multivariate twin study
      of Finnish men.
AB  - Of the 80% variation in BMD among male twins that is caused by genetics, part was
      explained by genetic influences on lifting strength and lean body mass/height.
      Lifting strength was significant in both the femoral and spine BMD and body
      weight only for lumbar BMD. INTRODUCTION: The dominant role of heritability in
      BMD has been shown in twin studies among women. However, the mechanisms of
      genetic influences are poorly understood. BMD is associated with lean body mass
      and muscle strength, which both have a genetic component, but the relative
      effects of muscle strength and lean body mass/height on the total genetic and
      environmental variations influencing BMD of men are unclear. MATERIALS AND
      METHODS: Measurements of BMD from a DXA scanner on a representative sample of 147
      monozygotic and 153 dizygotic male twin pairs (age, 35-70 yr) were related to a
      variety of anthropometric and behavioral covariates and interview data. Data were
      analyzed with univariate modeling of genetic characteristics, bivariate modeling
      of covariates that were significant in univariate models, and multivariate
      modeling of the simultaneous effects of significant covariates from the bivariate
      models. RESULTS: Heritability influences were estimated to account for 75% of the
      variance in femoral BMD and 83% in lumbar BMD. Univariate and bivariate modeling
      showed that, of the factors studied, only lifting force and lean body mass/height
      had statistically significant influences. Of the total genetic variation in
      femoral BMD, lifting force explained 9%, and lean body mass/height 18%; the
      proportions for lumbar BMD were 9% and 11%, respectively. Of the total
      environmental variation, the correlation with isokinetic lifting force explained
      9% for femoral BMD and 10% for lumbar BMD. The genetic correlations between
      lifting force and femoral and lumbar BMD were approximately 0.3, as were the
      environmental correlations of isokinetic lifting force and femoral and lumbar BMD
      and of lean body mass/height and femoral BMD. The environmental correlation of
      lean body mass/height and femoral BMD was not significant. CONCLUSIONS: Lifting
      force had effects on both femoral and lumbar BMD. Body weight was important, but
      only for lumbar BMD. Muscle strength may have the best potential for modification
      among behavioral factors to increase both femoral and lumbar BMD.

PMID- 17547537
TI  - Monitoring teriparatide-associated changes in vertebral microstructure by high
      resolution CT in vivo: results from the EUROFORS study.
AB  - We introduce a method for microstructural analysis of vertebral trabecular bone
      in vivo based on HRCT. When applied to monitor teriparatide treatment, changes in
      structural variables exceeded and were partially independent of changes in
      volumetric BMD. INTRODUCTION: Monitoring of osteoporosis therapy based solely on
      bone densitometry is insufficient to assess anti-fracture efficacy. Assessing
      bone microstructure in vivo is therefore of importance. We studied whether it is
      possible to monitor effects of teriparatide on vertebral trabecular
      microstructure independent of BMD by high-resolution CT (HRCT). MATERIALS AND
      METHODS: In a subset of 65 postmenopausal women with established osteoporosis who
      participated in the EUROFORS study, HRCT scans of T(12), quantitative CT of L(1)
      L(3), and DXA of L(1)-L(4) were performed after 0, 6, and 12 mo of teriparatide
      treatment (20 microg/d). We compared BMD and 3D microstructural variables in
      three groups of women, based on prior antiresorptive treatment: treatment-naive;
      pretreated; and pretreated women showing inadequate response to treatment.
      RESULTS: We found statistically highly significant increases in most
      microstructural variables and BMD 6 mo after starting teriparatide. After 12 mo,
      apparent bone volume fraction (app. BV/TV) increased by 30.6 +/- 4.4% (SE), and
      apparent trabecular number (app. Tb.N.) increased by 19.0 +/- 3.2% compared with
      6.4 +/- 0.7% for areal and 19.3 +/- 2.6% for volumetric BMD. The structural
      changes were partially independent of BMD as shown by a significantly larger
      standardized increase and a standardized long-term precision at least as good as
      DXA. Patients who had shown inadequate response to prior osteoporosis treatment
      did show improvements in BMD and structural measures comparable to treatment
      naive patients. CONCLUSIONS: HRCT is a feasible method for longitudinal
      microstructural analysis of human vertebrae in vivo, offers information beyond
      BMD, and is sufficiently precise to show profound effects of teriparatide after
      12 mo.

PMID- 17547538
TI  - Induction of labor with oral misoprostol for premature rupture of membranes at
      term in women with unfavorable cervix.

PMID- 17547539
TI  - Does maternal docosahexaenoic acid supplementation during pregnancy and lactation
      lower BMI in late infancy?
AB  - We compared growth of infants whose mothers either did or did not receive
      docosahexaenoic acid (DHA) supplements during pregnancy and lactation. At 21
      weeks' gestation, 144 women were enrolled into a randomized, double-blind
      clinical trial receiving: (1) a basic supplement consisting of vitamins and
      minerals (BS), or (2) BS plus 4.5 g fructooligosaccharide (BSF), or (3) BSF plus
      fish oil DHA (200 mg) until the end of the third month of lactation. Infants'
      length, weight and head circumference were measured at birth and at 1, 3 and 21
      months. A total of 51 mothers/infants were lost to follow-up by the third month
      and 24 at 21 months. The two groups not receiving DHA were combined into a
      control group. Analysis with mixed models adjusted for confounding factors showed
      a significant time dependent effect for the DHA group on the development of the
      body mass index (BMI) (P=0.037), and of weight (P=0.046), but no effect on the
      development of length (P=0.537), or of head circumference (P=0.267). At 21
      months, weight of the DHA group was lower by -601 g (95% CI -171; -1030 g) and
      BMI was lower by -0.76 kg/m(2) (95% CI -0.07; -1.46) compared to controls. The
      results indicate that DHA taken by pregnant and lactating mothers may reduce BMI
      in late infancy.

PMID- 17547540
TI  - Risk factors and outcomes for ventilator-associated pneumonia in neonatal
      intensive care unit patients.
AB  - In order to determine the risk factors and outcomes of ventilator-associated
      pneumonia (VAP) in the neonatal intensive care unit (NICU), a retrospective
      cohort study was conducted on 259 patients who were ventilated >48 h. Clinical
      characteristics and risk factors were compared and non-conditional logistic
      regression analysis was performed to determine independent predictors for VAP.
      There were 52 episodes of VAP (20.1%). The main pathogens were G(-) bacterium
      (82.1%, 23/28). Hospital stay in the VAP group was 19.9+/-5.9 vs. 16.7+/-7.2 days
      in controls (P<0.01). The mortality rate of the VAP group was 13.5% (7/52) vs.
      12.1% in controls (P>0.05). By logistic regression analysis the following
      independently predicted VAP: re-intubation (OR 5.3, 95% CI 2.0, 14.0), duration
      of mechanical ventilation (OR 4.8, 95% CI 2.2, 10.4), treatment with opiates (OR
      3.8, 95% CI 1.8, 8.5) and endotracheal suctioning (OR 3.5, 95% CI 1.6, 7.4). VAP
      occurred at significant rates among mechanically ventilated NICU patients and is
      associated with care procedures. The risk factors of neonatal VAP were re
      intubation, duration of mechanical ventilation, treatment with opiates and
      endotracheal suctioning. Additional studies are necessary to develop
      interventions to prevent neonatal VAP.

PMID- 17547541
TI  - Challenges in cancer control in Australia.
AB  - Despite advances in treatment, the greatest gains in cancer control are achieved
      through prevention.

PMID- 17547542
TI  - Rheumatic fever and social justice.
AB  - High rates of this disease are the face of Indigenous disadvantage.

PMID- 17547543
TI  - Experience with cardiac valve operations in Cape York Peninsula and the Torres
      Strait Islands, Australia.
AB  - OBJECTIVE: To describe the outcome of valve surgery, for rheumatic heart disease
      (RHD) and non-RHD, in residents of Cape York Peninsula and the Torres Strait
      Islands referred to the Cairns Base Hospital specialist outreach service. DESIGN
      AND PARTICIPANTS: Retrospective review of medical records on all patients
      residing in the outreach area who had surgery for valvular heart disease between
      1 January 1992 and 31 December 2004. MAIN OUTCOME MEASURES: Operation type and
      perioperative characteristics; 5- and 10-year survival rates; reoperation rates;
      complications. RESULTS: Forty-seven patients met the selection criteria; the
      median age was 40 years (range, 4-76 years); and 39 patients were Indigenous. RHD
      was the predominant cause of valve dysfunction (30/47 patients). Thirty-seven
      patients had valve replacements, six had valve repair and four had balloon
      valvotomy as the initial procedure. There were three bleeding complications, two
      episodes of operated valve endocarditis, and six embolic complications. There
      were nine valve-related deaths (six in the first 5 years). At 5 years, all seven
      patients who had had valve repair or balloon valvotomy were alive. Seven of the
      47 patients required reoperation. Survival analysis showed freedom from valve
      related deaths to be 83% (95% CI, 66%-92%) at 5 years and 61% (95% CI, 33%-80%)
      at 10 years. Freedom from reoperation at 5 years was 88% (95% CI, 71%-95%). Among
      the 30 patients with RHD, freedom from valve-related death was 80% (95% CI, 60%
      92%) at 5 years and 52% (95% CI, 21%-75%) at 10 years. In patients with RHD,
      freedom from reoperation at 5 years was 87% (95% CI, 65%-96%). CONCLUSION:
      Valvular heart disease results in substantial morbidity and mortality, despite
      intervention. Efforts need to focus on prevention of rheumatic fever and closer
      follow-up.

PMID- 17547545
TI  - Job satisfaction of staff and the team environment in Australian general
      practice.
AB  - OBJECTIVE: To study the work satisfaction of general practice staff, the
      differences between types of staff, and the individual and organisational factors
      associated with work satisfaction. DESIGN, SETTING AND PARTICIPANTS: Cross
      sectional multipractice study based on a self-completed job satisfaction survey
      of 626 practice staff in 96 general practices in Australia between 16 December
      2003 and 8 October 2004. MAIN OUTCOME MEASURES: Job satisfaction scores for all
      staff and for general practitioners alone; relationship between job satisfaction
      and the team climate, practice size, particular jobs within practices,
      demographic characteristics of participants, and geographical location of
      practices. RESULTS: The response rate was 65%. Job satisfaction was high, with a
      mean score of 5.66 (95% CI, 5.60-5.72). Multilevel analysis showed that all
      general practice staff were highly satisfied if they worked in a practice with a
      good team climate. Practice managers reported the highest satisfaction with their
      work. Practice size and individual characteristics such as the sex of the
      participant were unrelated to job satisfaction. GPs tended to have lower
      satisfaction than other staff in relation to income, recognition for good work
      and hours of work. Rural GPs were more satisfied. CONCLUSIONS: Most general
      practice staff are satisfied with their work. Facilitating teamwork may be a key
      strategy for both recruitment and retention of the general practice workforce,
      especially staff who are not GPs.

PMID- 17547544
TI  - The epidemiology of invasive group A streptococcal disease in Victoria,
      Australia.
AB  - OBJECTIVE: To estimate the incidence and severity of invasive group A
      streptococcal infection in Victoria, Australia. DESIGN: Prospective active
      surveillance study. SETTING: Public and private laboratories, hospitals and
      general practitioners throughout Victoria. PATIENTS: People in Victoria diagnosed
      with group A streptococcal disease notified to the surveillance system between 1
      March 2002 and 31 August 2004. MAIN OUTCOME MEASURE: Confirmed invasive group A
      streptococcal disease. RESULTS: We identified 333 confirmed cases: an average
      annual incidence rate of 2.7 (95% CI, 2.3-3.2) per 100,000 population per year.
      Rates were highest in people aged 65 years and older and those younger than 5
      years. The case-fatality rate was 7.8%. Streptococcal toxic shock syndrome
      occurred in 48 patients (14.4%), with a case-fatality rate of 23%. Thirty cases
      of necrotising fasciitis were reported; five (17%) of these patients died. Type 1
      (23%) was the most frequently identified emm sequence type in all age groups. All
      tested isolates were susceptible to penicillin and clindamycin. Two isolates (4%)
      were resistant to erythromycin. CONCLUSION: The incidence of invasive group A
      streptococcal disease in temperate Australia is greater than previously
      appreciated and warrants greater public health attention, including its
      designation as a notifiable disease.

PMID- 17547546
TI  - A case for universal salt iodisation to correct iodine deficiency in pregnancy:
      another salutary lesson from Tasmania.
AB  - OBJECTIVE: To assess the impact of iodine fortification of bread on the iodine
      status of pregnant women, and to determine if studies of iodine levels in school
      age children were indicative of women's gestational iodine status. DESIGN:
      Urinary iodine surveys of pregnant Tasmanian women before and after bread was
      fortified with iodine in October 2001. PARTICIPANTS AND SETTING: 285 women
      attending the Royal Hobart Hospital (RHH) antenatal clinic from 1 October 2000 to
      30 September 2001 and 517 women attending the RHH antenatal clinic or primary
      health care centres in 2003-2006. MAIN OUTCOME MEASURES: Median urinary iodine
      concentration (UIC) for comparison against the World Health Organization
      recommendation of of 150-249 microg/L for pregnant women. RESULTS: Before
      supplementation, the median UIC of the 285 women attending the RHH antenatal
      clinic was 76 microg/L. After supplementation, median UICs were 81 microg/L for
      288 women attending primary health care centres and 86 microg/L for 229 women
      attending the RHH antenatal clinic. Differences in mean UIC were not significant
      for either the antenatal clinic group (P=0.237) or the primary health care group
      (P=0.809) compared with the pre-supplementation group. CONCLUSIONS: Iodine
      deficiency in pregnancy persists despite being corrected in Tasmanian children.
      Successful iodine supplementation must target reproductive-age and pregnant women
      and be substantiated by ongoing monitoring during pregnancy and lactation. A
      robust national program for correcting iodine deficiency is urgently needed.
      Mandatory universal salt iodisation has international endorsement, and should be
      considered the preferred strategy for eliminating iodine deficiency in Australia.

PMID- 17547547
TI  - Hospital utilisation among people born in refugee-source countries: an analysis
      of hospital admissions, Victoria, 1998-2004.
AB  - OBJECTIVE: To investigate whether hospital utilisation and health outcomes in
      Victoria differ between people born in refugee-source countries and those born in
      Australia. DESIGN AND SETTING: Analysis of a statewide hospital discharge dataset
      for the 6 financial years from 1 July 1998 to 30 June 2004. Hospital admissions
      of people born in eight countries for which the majority of entrants to Australia
      arrived as refugees were included in the analysis. MAIN OUTCOME MEASURES: Age
      standardised rates and rate ratios for: total hospital admissions; emergency
      admissions; surgical admissions; total days in hospital; discharge at own risk;
      hospital deaths; admissions due to infectious and parasitic diseases; and
      admissions due to mental and behavioural disorders. RESULTS: In 2003-04, compared
      with the Australia-born Victorian population, people born in refugee-source
      countries had lower rates of surgical admission (rate ratio [RR], 0.85; 95% CI,
      0.81-0.88), total days in hospital (RR, 0.74; 95% CI, 0.73-0.75), and admission
      due to mental and behavioural disorders (RR, 0.70; 95% CI, 0.65-0.76). Over the 6
      year period, rates of total days in hospital and rates of admission due to mental
      and behavioural disorders for people born in refugee-source countries increased
      towards Australian-born averages, while rates of total admissions, emergency
      admissions, and admissions due to infectious and parasitic diseases increased
      above the Australian-born averages. CONCLUSIONS: Use of hospital services among
      people born in refugee-source countries is not higher than that of the Australian
      born population and shows a trend towards Australian-born averages. Our findings
      indicate that the Refugee and Humanitarian Program does not currently place a
      burden on the Australian hospital system.

PMID- 17547548
TI  - An Australian guideline for rheumatic fever and rheumatic heart disease: an
      abridged outline.
AB  - Acute rheumatic fever (ARF) and rheumatic heart disease (RHD) are diseases of
      poverty. They occur at world-record rates in Indigenous Australians, yet
      individual cases are often poorly managed, and most jurisdictions with high rates
      of these diseases do not have formal control strategies in place. New Australian
      guidelines formulated in 2005 by the National Heart Foundation of Australia and
      the Cardiac Society of Australia and New Zealand for diagnosis and management of
      ARF and RHD are a valuable resource for clinicians and policymakers. Key
      recommendations of the guidelines include: New diagnostic criteria for ARF in
      high-risk populations, including Indigenous Australians, which include
      echocardiographic evidence of subclinical valvular disease, and polyarthralgia or
      aseptic monoarthritis as major manifestations. Clear guidance about treatment of
      ARF. Non-steroidal anti-inflammatory drugs should be withheld until the diagnosis
      is confirmed, and corticosteroids may be an option in severe acute carditis. Most
      cases of chorea do not require medication, but use of carbamazepine or sodium
      valproate is recommended if medication is needed. Clear guidance about dose,
      dosing frequency and duration of secondary prophylaxis. Benzathine penicillin G
      is the preferred medication for this purpose. Establishment of a coordinated
      control program for all regions of Australia where there are populations with
      high prevalence of ARF and RHD. Key elements and indicators for evaluation are
      recommended. Active screening and legislated notification of ARF and RHD, where
      possible. Development of a structured care plan for all patients with a history
      of ARF or with established RHD, to be recorded in the patient's primary health
      care record.

PMID- 17547549
TI  - New money for mental health: will it make things better for rural and remote
      Australia?
AB  - New Australian government funding for the Better Outcomes in Mental Health Care
      initiative is a significant step forward for mental health, with general
      practitioners now able to offer direct referrals to psychologists, social
      workers, occupational therapists and Aboriginal health workers. Incentives for
      better teamwork between GPs and other mental health professionals have been
      introduced, but may have unintended consequences, including an exacerbation of
      workforce shortages in rural and remote areas. Possible solutions to these
      shortages include rural scholarships for students in the mental health
      professions; recruitment and retention of students coordinated by university
      departments of rural health; better access to continuing professional
      development; and federally funded rural positions and additional financial
      incentives for rural mental health practitioners.

PMID- 17547550
TI  - The role of family and maternal factors in childhood obesity.
AB  - OBJECTIVE: To investigate the relationship between a child's weight and a broad
      range of family and maternal factors. DESIGN, SETTING AND PARTICIPANTS: Cross
      sectional data from a population-based prospective study, collected between
      January 2004 and December 2005, for 329 children aged 6-13 years (192 healthy
      weight, 97 overweight and 40 obese) and their mothers (n=265) recruited from a
      paediatric hospital endocrinology department and eight randomly selected primary
      schools in Perth, Western Australia. MAIN OUTCOME MEASURES: Height, weight and
      body mass index (BMI) of children and mothers; demographic information; maternal
      depression, anxiety, stress and self-esteem; general family functioning;
      parenting style; and negative life events. RESULTS: In a multilevel model,
      maternal BMI and family structure (single-parent v two-parent families) were the
      only significant predictors of child BMI z scores. CONCLUSION: Childhood obesity
      is not associated with adverse maternal or family characteristics such as
      maternal depression, negative life events, poor general family functioning or
      ineffective parenting style. However, having an overweight mother and a single
      parent (single-mother) family increases the likelihood of a child being
      overweight or obese.

PMID- 17547551
TI  - Medical professionalism: is it really under threat?
AB  - Recent publications on medical professionalism have created an impression of a
      medical profession under siege in several countries. These publications recommend
      a new approach to medical professionalism to assist the profession to respond to
      new challenges. I suggest that the issue is not one of failed professionalism,
      but a shift in the balance of the ethical responsibilities brought about by major
      changes in health care systems. This shift has not yet been accepted or responded
      to by the medical profession. Medical professionalism is not under threat in
      Australia. Stronger leadership is required to address this altered ethical
      balance in the responsibilities of doctors.

PMID- 17547552
TI  - Brucellosis mimicking Henoch-Schonlein purpura.
AB  - A young male immigrant from Syria with a vasculitic-appearing leg rash,
      asymmetrical polyarthritis, microscopic haematuria, and raised inflammatory
      markers was provisionally diagnosed with Henoch-Schonlein purpura. Skin biopsy
      showed leukocytoclastic vasculitis. Low-grade fevers persisted despite non
      steroidal anti-inflammatory therapy, and Brucella sp. was subsequently grown from
      both blood and synovial fluid aspirates. Further tests gave positive results for
      B. abortus, and triple antibiotic therapy produced a rapid clinical response.
      Cutaneous vasculitis has rarely been described in brucellosis, and this is the
      first report in the English medical literature of brucellosis mimicking Henoch
      Schonlein purpura.

PMID- 17547553
TI  - Ototoxic ear drops with grommet and tympanic membrane perforations: a position
      statement.

PMID- 17547554
TI  - Finger fracture mitral valvuloplasty: a tribute to the pioneers of cardiac
      surgery.

PMID- 17547556
TI  - Should clinical software be regulated?

PMID- 17547557
TI  - Lessons from the NHS National Programme for IT.

PMID- 17547559
TI  - Risk factors for red cell transfusion in adults undergoing coronary artery bypass
      surgery: a systematic review.
AB  - BACKGROUND AND OBJECTIVE: Identifying factors that can predict adults at high
      risk of receiving red blood cell transfusion during coronary artery bypass graft
      (CABG) surgery may aid in more efficient blood banking practices and may tailor
      blood conservation strategies for these adult patients. The objective was to
      identify clinical factors associated with increased red cell transfusion in
      adults undergoing CABG surgery. METHODS: A systematic review of the MEDLINE and
      HealthSTAR databases from 1966 to December 2005 was conducted. Citations
      containing the medical subject heading or textwords 'coronary artery bypass
      graft', 'CABG' and 'cardiovascular surgery' were combined with the medical
      subject headings or textwords 'transfusion' and 'blood transfusion'. RESULTS: A
      total of 2461 abstracts were retrieved. Twenty-one studies met the
      inclusion/exclusion criteria. Transfusion rates ranged from 7 to 97%. Several
      variables were identified that were associated with increased red cell
      transfusion rates including older age, female sex, low haemoglobin concentration
      or haematocrit value, renal insufficiency and urgent/emergent surgery. The
      strongest risk factor was the urgency of surgery (urgent or emergent surgery),
      which was associated with a 4x to 8x increase in transfusion rates compared to
      elective surgery. Increasing age and female sex increased the likelihood of
      transfusion by 1x to 3x and 2x, respectively. CONCLUSIONS: Increasing patient
      age, female sex, lower preoperative haemoglobin levels, as well as the urgency of
      the CABG surgery were associated with higher transfusion rates. Identifying risk
      factors for transfusion may allow for targeted use of blood conservation
      strategies, improved efficiency in blood utilization and informing adults at risk
      of transfusion.

PMID- 17547560
TI  - Oxygenating the microcirculation: the perspective from blood transfusion and
      blood storage.
AB  - Tissue oxygen delivery depends on red blood cell (RBC) content and RBC flow
      regulation in the microcirculation. The important role of the RBC in tissue
      oxygenation is clear from anaemia and the use of RBC transfusion which has saved
      many lives. Whether RBC transfusion actually restores tissue oxygenation is
      difficult to determine due to the lack of appropriate clinical monitoring
      techniques. Some patients with restored haemoglobin levels and stable
      haemodynamics still develop tissue hypoxia, emphasizing that, in addition to
      global parameters, local microcirculatory control mechanisms are also important
      in the restoration of tissue oxygenation. Both clinical and animal experimental
      studies have indicated that storage of RBC diminishes their ability to oxygenate
      the tissue. Several intrinsic RBC parameters that change during storage and might
      influence tissue oxygenation will be mentioned. The release of vasodilators from
      RBC that will alter blood flow during hypoxia, mediated by haemoglobin in the RBC
      that functions as an oxygen sensor, could be impaired during storage. A better
      understanding of hypoxia-induced vasodilator release from RBC might become a
      potential target for drug development and improve tissue oxygenation after
      transfusion.

PMID- 17547558
TI  - Alternative promoters and repetitive DNA elements define the species-dependent
      tissue-specific expression of the FMO1 genes of human and mouse.
AB  - In humans, expression of the FMO1 (flavin-containing mono-oxygenase 1) gene is
      silenced postnatally in liver, but not kidney. In adult mouse, however, the gene
      is active in both tissues. We investigated the basis of this species-dependent
      tissue-specific transcription of FMO1. Our results indicate the use of three
      alternative promoters. Transcription of the gene in fetal human and adult mouse
      liver is exclusively from the P0 promoter, whereas in extra-hepatic tissues of
      both species, P1 and P2 are active. Reporter gene assays showed that the proximal
      P0 promoters of human (hFMO1) and mouse (mFmo1) genes are equally effective.
      However, sequences upstream (-2955 to -506) of the proximal P0 of mFmo1 increased
      reporter gene activity 3-fold, whereas hFMO1 upstream sequences (-3027 to -541)
      decreased reporter gene activity by 75%. Replacement of the upstream sequence of
      human P0 with the upstream sequence of mouse P0 increased activity of the human
      proximal P0 8-fold. Species-specific repetitive elements are present immediately
      upstream of the proximal P0 promoters. The human gene contains five LINE (long
      interspersed nuclear element)-1-like elements, whereas the mouse gene contains a
      poly A region, an 80-bp direct repeat, an LTR (long terminal repeat), a SINE
      (short-interspersed nuclear element) and a poly T tract. The rat and rabbit FMO1
      genes, which are expressed in adult liver, lack some (rat) or all (rabbit) of the
      elements upstream of mouse P0. Thus silencing of FMO1 in adult human liver is due
      apparently to the presence upstream of the proximal P0 of L1 (LINE-1) elements
      rather than the absence of retrotransposons similar to those found in the mouse
      gene.

PMID- 17547561
TI  - Increase in recently acquired syphilis infections in English, Welsh and Northern
      Irish blood donors.
AB  - BACKGROUND AND OBJECTIVES: Syphilis can be transmitted by blood. We describe
      syphilis infections detected in blood donors and investigate the epidemiology of
      syphilis in English, Welsh and Northern Irish blood donors. MATERIALS AND
      METHODS: This article analyses routine surveillance data regarding syphilis
      infections in blood donors from England, Wales and Northern Ireland between 1998
      and 2004. Infections are classified as recently acquired or past syphilis and
      donor characteristics and trends examined. RESULTS: A total of 518 syphilis
      infected donors were identified; 40 had recently acquired infection and 407 had
      past syphilis (71 were unclassified). Thirteen times more recently acquired
      syphilis infections were identified among people who donated between 2002 and
      2004 compared to 1998 to 2001. Young, white and regular donors were most likely
      to have recently acquired syphilis infections. Heterosexual sex was the main risk
      exposure identified overall; in contrast, the greatest proportion of recently
      acquired infections were in men who have sex with men. CONCLUSION: The increase
      in recently acquired syphilis, although low, indicates that risky sexual
      behaviours are increasing in the blood donor population, with implications for
      the microbiological safety of blood. Continued vigilance is required by blood
      services as the risk of syphilis increases in the general population.

PMID- 17547562
TI  - Storage of buffy-coat-derived platelets in additive solutions at 4 degrees C and
      22 degrees C: flow cytometry analysis of platelet glycoprotein expression.
AB  - BACKGROUND: The aim of our in vitro study is to compare the effects on platelet
      membrane glycoproteins that play an important role in the main functions of
      platelets, when platelets are stored for a period of 21 days at 4 degrees C or 22
      degrees C. STUDY DESIGN AND METHODS: Platelet concentrates (PC) were prepared
      from pooled buffy-coats (BC) for paired studies (total eight pools from 80 BCs)
      by using the OrbiSac system. We divided each pool into two PCs and stored them at
      4 degrees C or 22 degrees C. RESULTS: The activation marker CD62 remained almost
      unchanged during storage in all units. The expression of CD63 was higher in PCs
      stored at 22 degrees C than in those stored at 4 degrees C. No significant
      difference in CD41 expression was detected over time. The expression of CD42b
      declined during storage and even more in PCs stored at 4 degrees C until day 21
      [day 14: mean flourscence intensity: 32.5 +/- 13.1 vs. 46.5 +/- 19.1], but the
      percentage of platelets expressing CD42b remained high in platelets stored at 4
      degrees C, but gradually decreased at 22 degrees C (day 14: 95.0 +/- 1.5 vs. 59.0
      +/- 9.9). Storage at 4 degrees C reduced the rate of glycolysis and maintained
      the pH better after day 10 than in PCs stored at 22 degrees C (day 14: 7.009 +/-
      0.067 vs. 7.233 +/- 0.125). The concentration of regulated upon activation of
      normal T-cells expressed and secreted was higher in PCs stored at 22 degrees C
      than at 4 degrees C (day 7: 414.7 +/- 32.3 vs. 49.6 +/- 19.0). No response to
      extent of shape change and no swirling were detected at 4 degrees C. CONCLUSION:
      Platelets stored at 4 degrees C retain their in vitro characteristics better than
      those stored at 22 degrees C, except for parameters that reflect changes in
      shape. Storage at 4 degrees C is not associated with an increased expression of
      glycoprotein (GpIb, GpIIb/IIIa) and platelet activation markers (CD62p and CD63)
      as compared with storage at 22 degrees C.

PMID- 17547563
TI  - Balance module allows consistent monitoring and documentation of the pooling
      process for nucleic acid amplification technology testing.
AB  - BACKGROUND AND AIMS: When performing minipool testing of blood donations for
      transfusion-transmissible viruses, it is crucial to correctly dispense plasma
      from each donation into the pools. However, concerns regarding the monitoring and
      documentation of the pooling process exist. METHODS: A balance module with a tube
      holder has been developed, which can be easily integrated into liquid handling
      platforms. The existing software monitors and evaluates every single dispensing
      from primary samples to the minipool to confirm liquid arrival. The weighing
      accuracy of the balance module is approximately 2 mg per dispensing episode.
      RESULTS: Ten thousand one hundred and fifty-six blood donations were tested on a
      Tecan Genesis RSP pipetting system. Thirty-one donations were not pipetted
      because the pipetting workstation identified a clot or sample shortage in the
      primary tube. The balance module exclusively detected another 18 mispipettings,
      which were outside of the acceptance criteria of 100 +/- 10%. The mean pipetted
      volume for these samples was 34.2 microl (range 0-87 microl). Visual inspection
      of the corresponding primary tubes showed blood clots, short sample or no
      apparent cause. The average deceleration of the pooling process, using the
      balance, was determined to be about 22%. CONCLUSIONS: With the novel liquid
      arrival check system, complete and consistent process documentation of pooling
      for nucleic acid amplification technology (NAT) testing is feasible. It enables
      blood banks to monitor and compare every single dispense made with predefined,
      required volumes. Results can be transferred to the laboratory information
      management system for automated selective exclusion of inaccurately dispensed
      samples. ONE SENTENCE SUMMARY: Monitoring and documenting the pooling process for
      NAT testing using a balance-based liquid arrival check system.

PMID- 17547564
TI  - Clinical effect of buffy-coat vs. apheresis platelet concentrates in patients
      with severe thrombocytopenia after intensive chemotherapy.
AB  - BACKGROUND AND OBJECTIVES: Therapeutic or prophylactic use of platelet
      concentrates (PC) is essential for patients with thrombocytopenia due to
      intensive chemotherapy for various malignancies. PC quality has been improved
      after introduction of storage containers that are more oxygen permeable than the
      second-generation PC containers. Consequently, shelf life of PCs at our blood
      bank has been extended to 6.5 days after monitoring each PC for bacterial
      contamination. In this prospective observational study, we compared apheresis PCs
      harvested by Amicus cell separator with buffy-coat (BC) PCs during storage for up
      to 6.5 days. MATERIALS AND METHODS: All PCs were collected from healthy volunteer
      donors and were prepared for routine clinical use. A total of 446 transfusion
      episodes with 688 PCs for 77 adult patients with oncological and haematological
      diseases were registered during a 13-month period. Outcome measures were
      corrected count increment after 1 h (CCI-1), after 18-24 h (CCI-2), and
      transfusion intervals. Transfusions were carried out after storage from 1.5 to
      6.5 days. RESULTS: Both CCI and the transfusion intervals decreased statistically
      significantly by increasing storage time after transfusions with apheresis PCs or
      BC PCs. However, less than 4% of the variation in CCI and transfusion interval
      could be explained by platelet storage time. There were no significant
      differences between BC PCs and apheresis PCs, regarding CCI and transfusion
      intervals. CONCLUSION: We can conclude that BC PCs are not inferior to apheresis
      PCs, and may serve the clinical purposes as well as apheresis PCs harvested by
      Amicus.

PMID- 17547565
TI  - Elastic plasma protein film blended with platelet releasate accelerates healing
      of diabetic mouse skin wounds.
AB  - BACKGROUND AND OBJECTIVES: The growth factors derived from platelets and plasma
      proteins mediate the wound-healing process that is characterized by the
      sequential migration and differentiation of several cell populations that give
      rise to angiogenesis, collagen synthesis, wound contraction, and re
      epithelialization. To evaluate the efficacy of the blood-derived factors in wound
      healing, we examined a novel wound dressing consisting of concentrated human
      plasma proteins and platelet releasate (CPPP). MATERIALS AND METHODS: To generate
      CPPP, plasma proteins and platelets in the peripheral blood (n = 5) were
      concentrated with the cold ethanol precipitation method. The thrombin obtained
      from the same blood unit and calcium chloride (CaCl(2)) were mixed to a
      concentrate. The CPPP has enough strength to dress cutaneous wounds and contains
      large amounts of cytokines and fibronectin. We applied the CPPP to excisional
      skin wounds in genetically healing-impaired model mice (n= 5) and the wounds were
      evaluated 10 days after the operation. RESULTS: The area of CPPP-treated wounds
      decreased significantly compared with that of the control wounds (65% vs. 94% of
      the original size, respectively, P= 0.032). The immunostained section revealed a
      striking effect of CPPP on vascularization compared with the control wounds (13.2
      vs. 2.7 vessels per mm(2) as mean vascular density observed in the sections,
      respectively, P= 0.013). CONCLUSIONS: Our results suggest that CPPP is a
      promising biologically active dressing for full-thickness skin wounds. CPPP can
      be an entirely autologous biological dressing, suggesting that it is free from
      the risk of transmission of pathogens through blood products.

PMID- 17547566
TI  - Predicting potential drop-out and future commitment for first-time donors based
      on first 1.5-year donation patterns: the case in Hong Kong Chinese donors.
AB  - BACKGROUND AND OBJECTIVES: Adequate blood supply is crucial to the health-care
      system. To maintain a stable donor pool, donation-promotion strategies should not
      only be targeted in recruitment but also focus on retaining donors to give blood
      regularly. A study using statistical modelling is conducted to understand the
      first 4-year donation patterns for drop-out and committed first-time blood donors
      and to build model for the donor-type identification based on their first 1.5
      year donation patterns. SUBJECTS AND METHODS: First-time whole blood (n= 20 631)
      adult donors recruited in year 2000 and 2001 in Hong Kong were observed for more
      than 4 years. Cluster analysis was first applied to group donor type by their
      similarities in donation behaviour under the surveillance period. A decision tree
      model based on a shorter surveillance period (1.5 years) is then built to predict
      the donor type. RESULTS: Three donation patterns - one-time, drop-out, and
      committed donor behaviour - were identified in cluster analysis. Three variables 
      donation frequencies in the first-year and in the half-year period after first
      year, and the number of donation centre visits in the following half year after
      first year, were able to predict drop-out donors with potential to become
      committed and committed donors with relatively lower donation frequency.
      CONCLUSIONS: The present statistical modelling is able to identify those donors
      with potential to become committed donors and those committed donors who can
      donate more frequently. This information is useful for development of targeted
      donor retention strategies.

PMID- 17547567
TI  - Evaluation of the utility of the HemoCue 301 haemoglobinometer for blood donor
      screening.
AB  - BACKGROUND AND OBJECTIVES: Reliable blood donor screening requires more accurate
      measure of haemoglobin (Hb) than by either copper sulphate or the haemoglobin
      colour scale. The HemoCue haemoglobinometer has established a method for this,
      but it is considerably more expensive; a modified version (HemoCue 301) has now
      been developed with a cheaper reagent-free cuvette for use in budget-restricted
      situations. This report describes evaluation of the performance, the assessment
      of reproducibility and accuracy of this modified analyser against the reference
      technique for Hb measurement. MATERIALS AND METHODS: Over 300 routine blood
      samples from specimens received routinely in a hospital laboratory were tested in
      accordance with the International Committee for Standardization in Haematology
      (ICSH) protocol. Accuracy and linearity were confirmed by the reference method
      with the WHO international haemoglobincyanide reference standard. Tests were also
      performed on selected samples for checking interference by biochemical
      abnormalities and leucocytosis. The effects of various sample storage conditions
      prior to testing were also tested. RESULTS: Ninety per cent of results were
      within 4% of true values, 96% within 6% and in only three cases was the deviation
      > 10%, due to interference by bilirubinaemia and/or C-reactive protein. At an Hb
      value of 120 g/l for donor selection, there were no cases where the method would
      have been misleading. CONCLUSION: HemoCue 301 provides a simple and reliable
      anaemia screen method, conforming to the requirements of CLIA'88 regulations; it
      is reliable for discriminating Hb values for donor acceptance. The main advantage
      is that the cuvettes are significantly cheaper than the previous models, and will
      not deteriorate in adverse climatic conditions.

PMID- 17547568
TI  - Transfusion-related acute lung injury and leucocyte-reacting antibodies.
AB  - BACKGROUND AND OBJECTIVES: Transfusion-related acute lung injury (TRALI) is
      underdiagnosed and underreported. This is why we present cases suspected for
      TRALI, in which leucocyte antibodies were examined. MATERIAL AND METHODS: We
      analysed 44 patients with respiratory insufficiency, related to transfusion, who
      met criteria of acute lung injury (ALI). Lymphocyte and granulocyte antibodies
      were examined in donors and patients by six methods. RESULTS: Based on recent
      trends, we divided patients into two groups: TRALI (without risk factors for ALI)
      and possible TRALI (with probable risk factors). The incidence of antibodies was
      68.2%, the majority were human leucocyte antigen (HLA) class I and/or II, the
      minority were non-specific granulocyte antibodies; half of all detected
      antibodies, however, reacted with granulocytes. Antibodies were found in 17
      donors (more often in TRALI than in possible TRALI) and in 19 patients (in four -
      suspected to be of the donor origin, which would diminish the number of
      antibodies to 15). In seven available cases, we observed cognate antigen and/or
      positive cross-match. In the majority of patients, TRALI occurred after
      transfusion of red cells, in 56.2%- stored above 14 days; all the units were non
      leucoreduced. Lookback in two donors showed that transfusions in 20 patients did
      not result in reported TRALI, even in the patient with cognate antigen.
      CONCLUSIONS: Our clinical observations suggest that to distinguish between TRALI
      and possible TRALI is difficult and the results are equivocal - it is worth
      considering whether it can be omitted. We have confirmed that antibodies are
      involved in TRALI, although their role is very complex. The role of stored red
      blood cells in the development of TRALI requires further observations in
      comparison with a control group of patients without TRALI.

PMID- 17547569
TI  - Interference with TRALI-causing anti-HLA DR alloantibody induction of human
      pulmonary microvascular endothelial cell injury by purified soluble HLA DR.
AB  - BACKGROUND AND OBJECTIVE: Antibodies to human leucocyte antigens (HLA) and human
      polymorphonuclear neutrophil (PMN) antigens are considered etiologic agents of
      transfusion-related acute lung injury (TRALI). The aim of this study was to
      clarify the role of anti-HLA DR antibodies in the pathophysiology of TRALI and
      the ability of purified soluble HLA DR (psHLA DR) to inhibit the release of
      cytokines in an in vitro model. MATERIALS AND METHODS: A coculture of human
      pulmonary microvascular endothelial cells (HMVEC) and monocytes in the presence
      of serum containing anti-HLA DR alloantibodies previously associated with cases
      of TRALI was used as an in vitro TRALI model. The release of leukotriene B(4)
      (LTB(4)) and tumour necrosis factor-alpha (TNF-alpha), the apoptosis of HMVECs
      were measured. RESULTS: The release of LTB(4) and TNF-alpha and apoptosis of
      HMVECs were observed in the model. The addition of psHLA DR markedly reduced the
      release of LTB(4) and TNF-alpha and inhibited apoptosis of HMVECs. CONCLUSION:
      These results support the critical role of anti-HLA DR alloantibodies in the
      pathogenesis of TRALI and suggest that the soluble HLA DR could inhibit TRALI
      development caused by anti-HLA DR alloantibodies.

PMID- 17547570
TI  - Report of the Second International Workshop on molecular blood group genotyping.
AB  - The second International Society of Blood Transfusion and International Council
      for Standardization in Haematology workshop on molecular blood group genotyping
      was held in 2006. Forty-one laboratories participated. Six samples were
      distributed: two representing DNA from transfusion-dependent patients for testing
      for all clinically important polymorphisms; two representing DNA from amniotic
      fluid for RhD, Rhc, and K testing; and two plasma samples from RhD-negative
      pregnant women for fetal RhD testing (only tested by 20 laboratories). Overall, a
      high level of accuracy was achieved by most of the laboratories, although the
      error rate caused by RHDPsi was not acceptable and needs to be addressed. With
      greater care and attention to detail, very high standards could be set for
      molecular blood group genotyping.

PMID- 17547571
TI  - Preoperative autologous blood donation in Spain (1994-2004).

PMID- 17547572
TI  - The ethics of blood management.

PMID- 17547573
TI  - The safety of electronic cross-match in patients with warm autoantibodies.

PMID- 17547578
TI  - Diagnosing bipolar disorder in trauma exposed primary care patients.
AB  - OBJECTIVES: Bipolar disorder (BD) is often under-recognized in non-psychiatric
      settings, especially in African Americans. The Mood Disorder Questionnaire (MDQ)
      is a screening instrument proposed to show adequate sensitivity and specificity
      for bipolar spectrum disorders. The current study is an examination of the
      usefulness of this instrument in a trauma exposed subgroup of mainly African
      American patients attending primary care clinics. METHODS: The sample is a part
      of a larger study exploring traumatic stress exposure and psychopathology.
      Consenting patients in 3 academically affiliated primary care clinics were asked
      to complete the MDQ. Ninety percent of the participants were African American.
      Diagnostic performance was determined in a trauma exposed subgroup by employing
      the Structured Clinical Interview for DSM-IV (SCID) as a gold standard. RESULTS:
      Of the total group of 579 participants, 178 (30.7%) screened positive for BD
      along with 77 (33.7%) of the 228 trauma exposed subjects who were SCID
      interviewed. Only 13 (27%) of the MDQ positives met SCID criteria for BD and were
      true positives. The sensitivity was 61.9% and the specificity was 69%, with a
      positive predictive value of 16.8% and a negative predictive value of 94.7%.
      CONCLUSIONS: The MDQ was found to have low specificity in a predominately African
      American group of trauma exposed patients attending primary care.

PMID- 17547579
TI  - Early identification and high-risk strategies for bipolar disorder.
AB  - OBJECTIVES: To describe and compare the relative merits of different
      identification strategies for individuals at risk for bipolar disorder (BPD).
      METHODS: Selective review of data that support early identification in BPD, with
      a particular focus on emerging clinical high-risk strategies. RESULTS: Early
      detection of individuals at risk for BPD can utilize genetic, endophenotypic and
      clinical methods. Most published work focuses on genetic familial endophenotypic
      risk markers for BPD. However, despite encouraging results, problems with
      specificity and sensitivity limit the application of these data to early
      prevention programs. In addition, offspring studies of BPD patients
      systematically exclude the majority of subjects without a first-degree bipolar
      relative. On the other hand, emerging work in the clinical-high-risk arena has
      already produced encouraging results. Although still preliminary, the
      identification of individuals in subsyndromal or attenuated symptom 'prodromal'
      stages of BPD seems to be an under-researched area that holds considerable
      promise deserving increased attention. Required next steps include the
      development of rating tools for attenuated and subsyndromal manic and depressive
      symptoms and of prodromal criteria that will allow prodromal symptomatology to be
      systematically studied in patients with recent-onset bipolar, as well as in
      prospective population-based phenomenology trials and attenuated symptom-based
      high-risk studies. CONCLUSIONS: Given the current limitations of each early
      identification method, combining clinical, endophenotypic and genetic strategies
      will increase prediction accuracy. Since reliable biological markers for BPD have
      not been established and since most patients with BPD lack a first-degree
      relative with this disorder, clinical high-risk approaches have great potential
      to inform early identification and intervention programs.

PMID- 17547580
TI  - Rates, types, and psychosocial correlates of legal charges in adolescents with
      newly diagnosed bipolar disorder.
AB  - OBJECTIVES: To examine the rates, types, and psychosocial correlates of legal
      charges in adolescents with newly diagnosed bipolar disorder (BD). METHODS:
      Adolescents (n = 80), between the ages of 12 and 21 years (mean = 15.6, standard
      deviation = 2.3), hospitalized for their initial manic or mixed episode of BD,
      were evaluated for the incidence of prior juvenile offending (i.e., legal
      charges). We examined potential psychosocial correlates associated with legal
      charges using chi-square, t-tests, and discriminant function analyses to
      determine if there were differences between adolescents who did and did not
      offend prior to their first manic episode. RESULTS: Juvenile antisocial behaviors
      were common (55%) for adolescents with newly diagnosed BD. Discriminant function
      analysis revealed that older age at first treatment (p < 0.01), sexual activity
      over the previous month (p < 0.05), therapeutic use of stimulants (p < 0.05), and
      anxiety disorders were the most significant factors to differentiate between
      bipolar adolescents who offended and those who did not (Wilks' lambda = 0.80, p <
      0.005). CONCLUSIONS: Our findings indicate that there are identifiable
      psychosocial correlates associated with antisocial behaviors in adolescents with
      newly diagnosed BD that may improve our understanding of juvenile antisocial
      behaviors.

PMID- 17547581
TI  - Is a lack of disgust something to fear? A functional magnetic resonance imaging
      facial emotion recognition study in euthymic bipolar disorder patients.
AB  - OBJECTIVES: To determine the neural responses invoked in the recognition of
      facial fear and disgust in euthymic bipolar patients as compared with healthy
      subjects. METHODS: This study examined 10 female euthymic bipolar patients, and
      10 suitably matched healthy subjects using functional magnetic resonance imaging
      (fMRI) while subjects were engaged in an explicit facial emotion recognition task
      involving fear, disgust and neutral expressions. The activation paradigm involved
      nominating the facial expression using specified response keys. Behavioural data
      were collected and analysed and both within-group (Fear versus Neutral; Disgust
      versus Neutral) and random-effects between-group analyses were performed on fMRI
      data using BrainVoyager (Brain Innovations, Maastricht, the Netherlands).
      RESULTS: Patients were equally accurate in identifying facial expressions as
      healthy subjects but were slower to respond, especially with respect to fear and
      disgust. Responses to fear and disgust (within-group analyses) resulted in
      activation of anticipated brain regions such as amygdala and insula,
      respectively. However, between-group random effects analysis revealed
      differential responses to both disgust and fear in both healthy subjects and
      euthymic bipolar patients such that euthymic bipolar patients responded largely
      to fear and healthy subjects responded more so to disgust. This partitioning of
      responsiveness was reflected by differential activation involving the hippocampus
      and amygdala. CONCLUSIONS: Greater responsiveness to fear with hippocampal
      activation in patients perhaps reflects recollection of traumatic events
      associated with past experiences of illness or simply the use of a more mnemonic
      (hippocampal) as opposed to affective (amygdala) approach when performing the
      task. It is possible that in bipolar disorder, prefrontal-subcortical network
      dysfunction that relegates neural processing to limbic regions is impaired and
      that clinically euthymic bipolar patients, although able to accurately and
      effectively identify emotions such as fear and disgust, are limited in their
      ability to interpret their salience. The implications of these findings are
      discussed.

PMID- 17547582
TI  - The nature of abnormal language processing in euthymic bipolar I disorder:
      evidence for a relationship between task demand and prefrontal function.
AB  - OBJECTIVES: Abnormal language processing is a consistent finding in bipolar
      disorder (BD). We used functional magnetic resonance imaging (fMRI) to
      investigate the core components of language processing as well as the impact of
      task demand in a group of bipolar subjects. METHODS: Twelve euthymic dextral male
      BD I participants receiving lithium monotherapy were matched with 12 controls.
      Groups were matched for age, years of education and estimated premorbid IQ. We
      employed a factorial design manipulating task demand (decision versus fluency)
      and task domain (phonetic versus semantic) to investigate differences in language
      processing between groups and across different task domains and requirements.
      Data were fitted to haemodynamic response models convolved to the experimental
      design. Group and task difference maps were generated. RESULTS: During the
      scanning session bipolar patients demonstrated significantly slower reaction
      times. However, groups demonstrated the same task accuracy except for one domain
      (phonetic decision). All participants activated regions known to be engaged by
      language tasks, but compared to controls the bipolar patients showed altered
      patterns of prefrontal activation which were related to the nature of the task,
      language processing, and increasing task demand. CONCLUSIONS: We have
      demonstrated abnormal prefrontal activation in bipolar patients across a range of
      language tasks with varying task demands.

PMID- 17547583
TI  - COMT genotype increases risk for bipolar I disorder and influences neurocognitive
      performance.
AB  - OBJECTIVES: Bipolar disorder (BPD) is an affective disorder characterized by
      episodes of depression and mania. Cognitive impairment in patients with BPD is
      common and recent data suggest that it may represent a trait-like feature of the
      illness, as it persists during periods of wellness and co-segregates in families
      of bipolar patients. This suggests an underlying genetic predisposition towards
      cognitive impairment in patients with BPD; however, there have been few studies
      investigating the effects of candidate genes on this symptom domain. The catechol
      O-methyl transferase (COMT) gene is located on chromosome 22q11 and is involved
      in the metabolism of dopamine and norepinephrine. A large body of evidence
      suggests that COMT is associated with cognitive performance in patients with
      schizophrenia and in healthy volunteers but there have been no reports of its
      relationship to cognition in BPD. METHODS: We genotyped 52 Caucasian bipolar I
      probands and 102 Caucasian healthy controls across four single nucleotide
      polymorphisms (SNPs) within the COMT gene and administered a cognitive screening
      battery. We first assessed the relationship between COMT genotype and diagnosis
      and then tested for effects on cognition. RESULTS: We observed a modest but
      significant association between SNP rs165599 and BPD I, with the g allele being
      over-represented in cases versus controls (odds ratio, OR = 2.41; allelic p =
      0.02; genotypic p = 0.04). Further, we found a relationship between the risk
      allele at this SNP and poorer performance on measures of verbal memory
      [California Verbal Learning Test (CVLT) Trials 1-5; p = 0.005, eta(2) = 0.07]
      particularly with regard to prefrontal aspects of learning (CVLT semantic
      cluster; p = 0.037, eta(2) = 0.04) in patients with BPD and in healthy controls.
      The common Val158Met polymorphism was not associated with diagnosis (p = 0.32) or
      cognition in our sample. CONCLUSIONS: These data suggest that COMT genetic
      variation at SNP rs165599 is associated with BPD I and influences prefrontal
      aspects of verbal memory in bipolar patients and healthy controls.

PMID- 17547584
TI  - Heterogeneity of the risk of suicidal behavior in bipolar-spectrum disorders.
AB  - OBJECTIVES: The risk of suicidal behavior is substantially elevated in major
      affective disorders (AD). In bipolar disorder (BD), as many as 15% of patients
      may commit suicide and family history of suicide is recognized as one of the most
      important risk factors. Lithium reduces the rates of suicidal behavior in BD,
      especially in patients who achieve full mood stabilization. Yet even patients who
      continue experiencing mood episodes do benefit from anti-suicidal properties of
      lithium. These observations raise questions about the nature of the relationship
      between the neurobiological mechanisms of BD and suicide, namely whether they are
      shared or independent. METHODS: We studied the distribution of suicides and
      suicide attempts in 539 subjects from 78 families of probands with major AD, all
      responders to lithium prophylaxis. A Cox proportional hazard regression model was
      used to assess the contribution of several independent variables to the risks of
      AD, BD, and suicidal behavior. RESULTS: The lifetime prevalence of BD was
      significantly greater among first-degree relatives of suicide than non-suicide
      probands (22% versus 11%) and the prevalence of BD in families was associated
      with an increased risk of developing mood disorder and subsequently committing or
      attempting suicide (p = 0.003). Families fell into 1 of 3 groups, corresponding
      to a low (<0.1%), intermediate (17.8%), and high (87.8%) risk for suicide in
      affectively ill subjects. CONCLUSIONS: Suicidal behavior is distributed unevenly
      in families of probands with BD, aggregating in a subset of families. Our results
      also suggest that partially overlapping sets of genetic factors may underlie BD
      and suicide.

PMID- 17547585
TI  - Effects of treatment latency on response to maintenance treatment in manic
      depressive disorders.
AB  - OBJECTIVES: To further test the hypothesis that past illness episodes and delay
      of long-term treatment do not limit maintenance treatment response among patients
      with manic-depressive illnesses (MDI). METHODS: In a sample of 764 MDI patients
      in Cagliari and Berlin, 77% of whom had bipolar disorder (BPD), we: (i)
      correlated treatment latency or pretreatment episode counts versus hospitalized
      morbidity during treatment; (ii) correlated treatment duration versus
      pretreatment morbidity; (iii) correlated treatment latency versus pretreatment or
      treated morbidity; (iv) modeled factors associated with longer treatment latency;
      (v) compared treatment latencies at extremes of treatment outcomes, and (vi)
      compared pretreatment morbidity within 2 years of the longest versus shortest
      treatment latency quartiles. RESULTS: Pretreatment morbidity was strongly
      correlated with shorter treatment latency, but morbidity during treatment was
      unrelated to treatment latency, pretreatment episode counts, sex, diagnosis,
      treatment type or treatment duration. In multivariate modeling, treatment latency
      was longer among patients who had experienced an early onset of illness, mainly
      in depressive disorders (BPD II and major depression) and among women, but was
      unrelated to morbidity during treatment. Patients with no illness recurrences
      during treatment and those who were ill at least 50% of the time had similar
      treatment latencies. Pretreatment morbidity occurring just prior to the
      initiation of long-term treatment was very similar at the highest and lowest
      treatment latencies. CONCLUSIONS: These findings support the therapeutically
      favorable conclusion that prior episode counts and treatment delay have little
      association with morbidity during prophylaxis with mood-stabilizing agents.
      Comparisons of morbidity during versus before treatment in episodic disorders are
      misleading because overall morbidity becomes diluted with longer time-at-risk,
      whereas therapeutic intervention is typically determined by immediately preceding
      illness.

PMID- 17547586
TI  - Effectiveness of mood stabilizers and antipsychotics in the maintenance phase of
      bipolar disorder: a systematic review of randomized controlled trials.
AB  - BACKGROUND: Bipolar disorder (BD) is a leading cause of disability. Systematic
      reviews of randomized trials for the treatment of the maintenance phase of BD are
      lacking. OBJECTIVES: To determine the efficacy and tolerability of mood
      stabilizers and antipsychotics in the maintenance treatment of BD. METHODS: We
      systematically reviewed randomized controlled trials of licensed medications for
      the treatment of any phase of BD. We included randomized controlled trials
      comparing a medication to placebo or another medication. Comprehensive searches
      of electronic databases were conducted to March 2005. Outcomes investigated were
      relapse due to mania, depression or any mood episode, and withdrawal due to any
      reason or due to an adverse event. Data were combined through meta-analysis.
      RESULTS: Fourteen studies (n = 2,526) met the inclusion criteria. Lithium,
      lamotrigine, olanzapine and valproate semisodium each demonstrated evidence to
      support long-term use. Compared with placebo, all medications were more effective
      at preventing relapse because of any mood episode. Hazard ratios (HR) were 0.68
      [95% confidence interval (CI) = 0.53-0.86] for lithium, 0.68 (95% CI = 0.55-0.85)
      for lamotrigine, and 0.82 (95% CI = 0.57-1.20) for valproate semisodium; for
      olanzapine, the risk ratio (RR) was 0.58 (95% CI = 0.49-0.69). Lithium and
      olanzapine significantly reduced manic relapses (HR = 0.53; 95% CI = 0.35-0.79
      and RR = 0.37; 95% CI = 0.24-0.57, respectively). Lamotrigine and valproate
      semisodium significantly reduced depressive relapses (HR = 0.65; 95% CI = 0.46
      0.91 and RR = 0.40; 95% CI = 0.20-0.82, respectively). Lithium significantly
      reduced manic relapses compared with lamotrigine (HR = 0.56; 95% CI = 0.34-0.92)
      and olanzapine significantly reduced manic relapses compared with lithium (RR =
      1.69; 95% CI = 1.12-2.55). Withdrawal due to an adverse event was approximately
      twice as likely with lithium compared with valproate semisodium (RR = 1.81; 95%
      CI = 1.08-3.03) and lamotrigine (RR = 2.20; 95% CI = 1.31-3.70). There were few
      data for carbamazepine or medications given as adjunct therapy. CONCLUSIONS: Mood
      stabilizers have differing profiles of efficacy and tolerability, suggesting
      complementary roles in long-term maintenance treatment.

PMID- 17547587
TI  - Quetiapine monotherapy in the treatment of patients with bipolar I or II
      depression and a rapid-cycling disease course: a randomized, double-blind,
      placebo-controlled study.
AB  - OBJECTIVES: To investigate the efficacy and tolerability of quetiapine
      monotherapy in patients with bipolar I or II disorder with a rapid-cycling
      disease course. METHODS: Adult patients with a DSM-IV diagnosis of bipolar
      disorder, most recent episode depressed, with a rapid-cycling disease course from
      a previously completed multicenter trial randomized to 8 weeks of treatment with
      quetiapine 600 mg/day (n = 31), quetiapine 300 mg/day (n = 42), or placebo (n =
      35) were included in this sub-analysis. The primary efficacy variable was change
      from baseline to week 8 in Montgomery-Asberg Depression Rating Scale (MADRS)
      total score. RESULTS: Quetiapine (600 and 300 mg/day) provided significantly
      greater mean reductions from baseline to week 8 in the MADRS total score than
      placebo (-21.1, -20.7 versus -11.6, both p < 0.001) in this patient population.
      Effect sizes in patients with a rapid-cycling disease course were 1.2 (600
      mg/day) and 1.1 (300 mg/day) and were similar for bipolar I (0.98 and 1.22) and
      bipolar II (1.45 and 0.97) sub-groups. Significant improvements were also noted
      on the Clinical Global Impression, Hamilton Rating Scale for Depression, Hamilton
      Rating Scale for Anxiety, Pittsburgh Sleep Quality Index, and Quality of Life
      Enjoyment and Satisfaction Questionnaire scales. Quetiapine was generally well
      tolerated with moderate increases in weight and extrapyramidal side effects
      compared to placebo. The incidence of treatment-emergent mania was similar to
      placebo. CONCLUSIONS: Quetiapine monotherapy (600 or 300 mg/day) is clinically
      effective and well tolerated in the short-term treatment of depressive episodes
      in patients with bipolar I or II disorder who have a rapid-cycling disease
      course.

PMID- 17547588
TI  - A 24-week, randomized, controlled trial of adjunctive sibutramine versus
      topiramate in the treatment of weight gain in overweight or obese patients with
      bipolar disorders.
AB  - OBJECTIVES: Patients with bipolar disorder (BD) have an increased risk of obesity
      as well as psychotropic-associated weight gain. The objective of this study was
      to compare sibutramine and topiramate as adjunctive treatments for psychotropic
      associated weight gain in overweight or obese outpatients with BD. METHODS: In
      this 24-week, open-label, flexible-dose, comparison trial, 46 outpatients with
      bipolar disorders who had a body mass index (BMI) > or =30 kg/m(2), or > or =27
      kg/m(2) with obesity-related comorbidities, and psychotropic-associated weight
      gain were randomly assigned to receive sibutramine (n = 18; 5-15 mg/day) or
      topiramate (n = 28; 25-600 mg/day). The primary outcome measure was weight loss.
      Secondary measures included changes in BMI, percent body weight loss, and mood
      symptoms. RESULTS: Patients randomized either to sibutramine or topiramate lost
      comparable amounts of weight (4.1 +/- 5.7 and 2.8 +/- 3.5 kg, respectively) and
      displayed similar rates of weight loss (0.85 and 0.82 kg/week, respectively).
      However, only four (22%) patients receiving sibutramine and six (21%) patients
      receiving topiramate completed the 24-week trial. In addition, the attrition
      patterns for the two drugs were different, with patients discontinuing topiramate
      doing so early in treatment and patients discontinuing sibutramine doing so
      throughout treatment. Also, higher ratings of manic and depressive symptoms
      significantly increased risk for early topiramate discontinuation compared to
      that for sibutramine. CONCLUSIONS: Adjunctive sibutramine and topiramate may have
      comparable weight loss effects in overweight or obese bipolar patients with
      psychotropic-associated weight gain, but are each associated with similarly high
      discontinuation rates. In addition, they may have different attrition profiles.
      Compared to sibutramine, discontinuation of topiramate may be more likely to
      occur early in treatment and may be more dependent upon manic and depressive
      symptoms.

PMID- 17547590
TI  - Future trends in joint replacement and tissue engineering in small animal
      orthopedics.

PMID- 17547591
TI  - Outcomes based medicine in veterinary surgery: getting hard measures of
      subjective outcomes.

PMID- 17547592
TI  - Custom total knee replacement in a dog with femoral condylar bone loss.
AB  - OBJECTIVE: To report surgical planning, technique, and outcome of custom total
      knee replacement (TKR) performed to manage a medial femoral condylar nonunion in
      a dog. STUDY DESIGN: Clinical case report. ANIMAL: A 3-year-old, 20 kg Karelian
      Bear Hound. METHODS: Computed tomographic scan of the left pelvic limb was used
      to build a stereolithography model of the distal portion of the femur. The model
      was used to create a custom augment to replace the missing medial femoral condyle
      and a custom stem for intramedullary condylar cemented fixation. The augment and
      stem were adapted to femoral and tibial components already available. The model
      was used to rehearse the surgery and then the custom prosthesis was implanted.
      RESULTS: Weight bearing returned 8 hours after surgery and improved thereafter.
      Joint alignment was normal and prosthetic joint motion was 60-165 degrees
      postoperatively. The dog resumed moose hunting 3 months after surgery. Peak
      vertical force and impulse of the operated limb measured 17 months after surgery
      were 65% and 47% of the normal, contralateral limb. CONCLUSION: Based on short
      term follow-up, cemented canine TKR was successfully achieved for management of a
      severely abnormal stifle joint. CLINICAL RELEVANCE: With further refinement and
      development of commercially available prostheses, TKR should be possible for
      canine patients.

PMID- 17547593
TI  - Reclassification of small intestinal and cecal smooth muscle tumors in 72 dogs:
      clinical, histologic, and immunohistochemical evaluation.
AB  - OBJECTIVES: To reclassify canine small intestinal and cecal leiomyoma (LM) and
      leiomyosarcoma (LMS) into smooth muscle and gastrointestinal stromal tumors
      (GIST) using histologic and immunohistochemical (IH) analysis and to report
      clinical findings and survival data. STUDY DESIGN: Retrospective review of cases.
      ANIMALS: Dogs (n=47) with small intestinal (40 LMS; 7 LM) and 25 dogs with cecal
      tumors (23 LMS; 2 LM). METHODS: Clinical and survival data were reviewed. Tissue
      sections were reevaluated for light-microscopic malignancy criteria and examined
      for expression of SMA, desmin, vimentin, S-100, and CD117 (KIT) by
      immunohistochemistry. RESULTS: Reclassification resulted in 2 LM, 9 LMS, 19 GIST,
      and 17 GIST-like tumors in the small intestine and 23 GIST and 2 GIST-like tumors
      in the cecum. GIST-like tumors were morphologic and IH identical to GIST but
      lacked KIT expression. No significant difference in survival was observed for
      tumor type, location, histologic, or IH characteristics; however, dogs with cecal
      tumors were significantly older in age, presented more commonly with intestinal
      perforation and peritonitis, and less commonly with weight loss. Cecal tumors had
      more histologic malignancy criteria than small intestinal tumors. After excision,
      1 and 2 year recurrence-free periods were 80.1% and 67.2% for small intestinal
      and 83.3% and 61.9% for cecal tumors. CONCLUSION: Prognosis for intestinal tumors
      with histologic smooth muscle appearance is good after excision and not related
      to tumor type, location, histologic, or IH characteristics. CLINICAL RELEVANCE:
      Clinical importance could not be demonstrated for reclassification, but may be
      for future treatment, of intestinal smooth muscle or stromal tumors.

PMID- 17547594
TI  - Intraoperative radiation for limb sparing of the distal aspect of the radius
      without transcarpal plating in five dogs.
AB  - OBJECTIVES: To evaluate intraoperative irradiation (IORT) as a method of limb
      spare with preservation of the radiocarpal joint. STUDY DESIGN: Prospective case
      series. ANIMALS: Dogs (n=5) with stage II sarcoma of the distal aspect of the
      radius. METHODS: A bone segment containing the tumor was isolated surgically,
      treated by IORT, reimplanted, and secured by internal fixation. In 1 dog, the
      postradiation tumor bed was curetted and filled with bone cement. Dogs were
      administered alternating adriamycin and carboplatin starting 2 weeks after IORT
      and monitored at regular intervals. RESULTS: Four dogs had osteosarcoma and 1 had
      undifferentiated sarcoma. Implant failure (n=3), deep tissue infection (3), and
      pathologic fracture (3) resulted in amputation (3) or pancarpal plating (2). The
      dog with undifferentiated sarcoma was euthanatized because of suspected tumor
      recurrence 4 months postoperatively. Osteotomy healing was documented by
      radiography (1), histopathology (2), or by direct observation (2). CONCLUSIONS: A
      technique for limb-sparing surgery of the distal portion of the radius in dogs
      using IORT had advantages include healing of the autograft and a source for a
      perfectly fitting autograft but did not appear to offer any advantage with
      respect to infection rate. Long-term preservation of the radiocarpal joint was
      not successful. CLINICAL RELEVANCE: It was not possible to preserve the function
      of the radiocarpal joint and so this technique cannot be recommended currently.
      Further study is needed to evaluate whether or not IORT can be considered in
      combination with pancarpal plating and possibly curettage and cementation of the
      tumor to prevent subchondral bone collapse.

PMID- 17547595
TI  - Transverse ulnar bone transport osteogenesis: a new technique for limb salvage
      for the treatment of distal radial osteosarcoma in dogs.
AB  - OBJECTIVE: To develop instrumentation and a technique for transverse ulnar bone
      transport osteogenesis in dogs. STUDY DESIGN: Cadaveric study and in vivo
      validation (1 dog). SAMPLE POPULATION: Paired cadaveric antebrachii (n=10 dogs)
      and 1 live dog. METHODS: Circular fixator constructs were applied and fitted with
      reeling or linear motors designed to transport an ulnar segment transversely into
      a defect created by excising the distal 50% of the ipsilateral radius. A
      longitudinal osteotomy of the adjacent ulna was created and the segment was
      transported across the radial defect. Pre- and post-distraction CT scans were
      used to compare the efficacy of each construct. The procedure was performed
      unilaterally in a live dog using the reeling motor (RM) construct. RESULTS: Both
      constructs effectively transported the ulnar segment into the defect.
      Subjectively, the RMs were easier to apply and operate. No significant
      differences were observed in the objective measures of efficacy between the 2
      construct types. The live dog produced viable regenerate bone after transverse
      ulnar bone transport. CONCLUSIONS: Transverse ulnar bone transport should be
      considered a potential method for limb salvage in dogs with osteosarcoma (OSA) of
      the distal radius. The RMs were effective and clinically applicable. CLINICAL
      RELEVANCE: Transverse ulnar bone transport osteogenesis affords the benefits of
      longitudinal radial bone transport osteogenesis, allowing resolution of large
      longitudinal radial defects in a substantially less time as a result of
      shortening the transport distance. This would be beneficial when treating
      conditions such as OSA where minimizing convalescence and maximizing quality of
      life is a priority.

PMID- 17547596
TI  - Effect of 9 mm tibial tuberosity advancement on cranial tibial translation in the
      canine cranial cruciate ligament-deficient stifle.
AB  - OBJECTIVE: To assess the effect of 9 mm tibial tuberosity advancement (TTA) on
      cranial tibial translation (CTT) in a cranial cruciate ligament (CCL)-deficient
      canine stifle model. STUDY DESIGN: In vitro cadaveric study. ANIMALS: Canine
      pelvic limbs (n=12). METHODS: Each stifle was placed in a jig at 135 degrees with
      a simulated quadriceps force and tibial axial force. CTT distance was measured
      with the CCL intact (iCCL), transected (tCCL), and after performing TTA using a 9
      mm cage. RESULTS: Mean CTT for iCCL was 0.42 mm, 1.58 mm after severing the CCL,
      and 1.06 mm post-TTA. The tCCL CTT measured without any quadriceps force was 2.59
      mm. Differences between the intact and tCCL (P<.0001) and tCCL and TTA (P=.0003)
      were significant. The difference between the tCCL with and without the quadriceps
      force was not significant (P=.0597). CONCLUSIONS: These data confirm that TTA
      does reduce CTT in tCCL stifles in this model. The CTT noted was less than that
      noted clinically. The addition of a simulated quadriceps force to a CCL-deficient
      stifle before a TTA, by itself, may not significantly lessen CTT. CLINICAL
      RELEVANCE: Whereas this in vitro model demonstrated that TTA reduced CTT in
      canine stifles with CCL transected, the model limitations preclude extrapolation
      to the effect of TTA in a live dog.

PMID- 17547597
TI  - Surgical stapling devices in veterinary medicine: a review.
AB  - OBJECTIVES: To review indications, benefits, and complications of surgical
      stapling in animals. STUDY DESIGN: Literature review. RESULTS: Benefits and
      complications of surgical stapling depend on the procedure performed. Use of
      surgical staplers does not improve wound strength but may decrease surgical time.
      CLINICAL RELEVANCE: In patients at significant risk for intraoperative
      contamination or morbidity from prolonged anesthesia time, use of stapling
      devices should be considered.

PMID- 17547598
TI  - Septic arthritis of the distal interphalangeal joint in cattle: comparison of
      digital amputation and joint resection by solar approach.
AB  - OBJECTIVE: To determine in cattle with septic arthritis of the distal
      interphalangeal joint (SADIJ) the efficacy of resection of the distal
      interphalangeal joint (JRES) as a digit salvage technique compared with digital
      amputation (DAMP). STUDY DESIGN: Prospective, randomized clinical study. ANIMALS:
      German Holstein-Friesian dairy cattle with SADIJ of 1 hind limb (n=52). METHODS:
      SADIJ diagnosis was based on clinical examination and radiography. Cows were
      randomly assigned with owner consent to DAMP (n=26) or JRES (n=26). After JRES, a
      wooden block was fixed to the partner claw in combination with a tipping claw
      prophylaxis. RESULTS: After surgery, degree of lameness improved significantly
      faster after DAMP than after JRES. New claw diseases in the opposite limb
      occurred more frequently after JRES (n=6) than after DAMP (n=1). New claw defects
      developed in the partner claw on the operated limb in 6 cows after DAMP compared
      with 1 after JRES. Tipping claw was observed in 50% of JRES cows at day 180. Mean
      life span between groups was not significantly different (DAMP=13.5 months,
      JRES=10.9 months). CONCLUSION: Higher surgical and postsurgical expenditures for
      JRES were not counterbalanced by a longer productive life; however, frequent
      disease of the partner claw of cows after DAMP should be considered a critical
      point, as this generally leads to culling. CLINICAL RELEVANCE: The higher
      expenditure for JRES can be justified only for young, valuable cattle.

PMID- 17547599
TI  - Evaluation of agreement between numerical rating scales, visual analogue scoring
      scales, and force plate gait analysis in dogs.
AB  - OBJECTIVE: To evaluate the accuracy of numerical rating (NRS) and visual analogue
      (VAS) scoring scales compared with force plate gait analysis and agreement
      between observers for each scoring scale. STUDY DESIGN: Experimental study.
      ANIMALS: Mixed breed dogs (n=21) with a right limb tibial osteotomy repaired with
      an external fixator. METHODS: Three small-animal veterinarians with orthopedic
      training scored lameness using NRS and VAS before surgery, and at 4 and 8 weeks
      after surgery. Peak force and impulse were determined at the same time points
      using a force plate. Agreement between observers and with force plate data was
      assessed. Significance was set at P< or =.05. RESULTS: Agreement was generally
      low among observers for both NRS and VAS scores. When evaluated at each time
      point, an acceptable level of agreement was present only at 4 weeks after
      surgery. Only impulse had a significant relationship with some of the observers'
      subjective scores. No significant relationships between any observer's scores and
      force plate data existed if very lame dogs were omitted. CONCLUSIONS: Subjective
      scoring scales do not replace force plate gait analysis. Agreement is low unless
      lameness is severe, and each observer uses an individually unique scale.
      Subjective scoring scales most accurately reflect force plate gait analysis when
      lameness is severe. CLINICAL RELEVANCE: Subjective lameness scoring scales may
      not accurately reflect lameness and do not replace force plate gait analysis.
      Observers must stay the same during the duration of a study for accurate
      analyses.

PMID- 17547600
TI  - In vitro mechanical comparison of screwed, bolted, and novel interlocking nail
      systems to buttress plate fixation in torsion and mediolateral bending.
AB  - OBJECTIVE: To compare standard interlocking nails (ILN) with a newly designed ILN
      featuring an angle-stable locking mechanism (ILNn). STUDY DESIGN: Six
      experimental groups. SAMPLE POPULATION: Bone models (n=48) treated with 6 and 8
      mm nails locked with screws or bolts (ILN6s, ILN8s, ILN6b, ILN8b, respectively),
      ILNn, and a 3.5 mm broad-DCP (br-DCP); n=4/testing mode. METHODS: Specimens were
      tested in torsion or 4-point bending. Construct compliance, deformation, and
      slack were statistically compared (P<.05). RESULTS: Regardless of testing mode,
      construct compliance was greater with smaller ILN. Screwed constructs were more
      compliant than bolted ones, with a significant difference between ILN6s and ILN6b
      in torsion. Plated constructs were significantly more compliant than the ILNn.
      Angular deformation was consistently greater with smaller ILN. Screwed ILN
      constructs sustained approximately 2 x the torsional deformation of the bolted
      ones (approximately 36 degrees [ILN6s] versus approximately 18 degrees [ILN6b]).
      Comparatively, ILNn constructs had significantly less torsional (approximately 8
      degrees) and bending (approximately 4 degrees) deformation than other constructs.
      Whereas standard ILN constructs had slack in both modes, ILNn and br-DCP
      construct deformations consistently occurred without slack. CONCLUSIONS: Use of
      bolts rather than screws improved ILN mechanical behavior, but neither locking
      mechanism completely counteracted torsion and bending forces. Conversely, the
      ILNn angle-stable locking system eliminated torsional and bending slack,
      resulting in comparable mechanical performances between ILNn and plated
      constructs. CLINICAL RELEVANCE: The angle-stable locking mechanism of the new ILN
      eliminates all slack in the system; thus, interfragmentary motion will likely be
      reduced compared with standard ILN, which may improve the local environment for
      fracture healing.

PMID- 17547601
TI  - Repair of a longitudinal scapular fracture in a horse.
AB  - OBJECTIVE: To report repair of a longitudinal scapular fracture in a horse. STUDY
      DESIGN: Case report. ANIMALS: A 2-year-old Paint Horse colt. METHODS: A
      longitudinal scapular fracture was surgically repaired using four 4.5 mm dynamic
      compression plates. RESULTS: An acute longitudinal scapular fracture repaired
      surgically returned the horse to soundness within 6 months. CONCLUSIONS: Internal
      fixation of longitudinal scapular fracture is possible with multiple 3-5 hole
      dynamic compression plates. CLINICAL RELEVANCE: Longitudinal fractures of the
      scapula should be considered when there is lateral instability of the shoulder
      after trauma. A displaced fracture can be adequately stabilized by internal
      fixation with a reasonable prognosis for soundness.

PMID- 17547602
TI  - Intramedullary pinning of metacarpal and metatarsal fractures in cats using a
      simple distraction technique.
AB  - OBJECTIVE: To describe a simple technique of intramedullary (IM) pinning for open
      reduction and internal fixation of metacarpal and metatarsal fractures in cats
      and evaluate outcome. STUDY DESIGN: Retrospective study. ANIMALS: Cats (n=17).
      METHODS: Medical records of cats with metacarpal and metatarsal fractures treated
      by a specific IM pinning method with Kirschner wires were reviewed. Types of
      fractures and number of pins used were recorded. Pre- and postoperative
      radiographs were evaluated. Outcome was assessed based on clinical examination,
      evaluation of radiographs, and owner questionnaire. RESULTS: Seventeen
      questionnaires were evaluated. Thirteen cats had a final recheck and radiographic
      assessment. Eight cats were lost to follow-up. Sixteen owners (94%) reported no
      obvious change in their cat's gait after treatment. One owner reported excellent
      function in her cat despite a slightly abnormal gait because of bent implants.
      CONCLUSIONS: IM pinning after distraction of bone fragments is a reliable
      technique for treatment of metacarpal and metatarsal fractures in cats.
      Complications associated with fracture healing may or may not be associated with
      lameness. CLINICAL RELEVANCE: IM pinning used in conjunction with appropriate
      bandaging for 4 weeks yields excellent functional outcome for treatment of
      metacarpal and metatarsal fractures in cats. Metacarpo- and metatarsophalangeal
      joint damage is prevented using this technique.

PMID- 17547603
TI  - The effectiveness of transtelephonic monitoring of pacemaker function in
      pediatric patients.
AB  - BACKGROUND: To determine the sensitivity and specificity, rate of compliance, and
      predictors of failure of telephone transmission of pacemaker function in a
      pediatric population. METHODS: A total of 2,638 pacemaker transmission records
      were reviewed retrospectively. Standard calculations of sensitivity, specificity,
      and positive and negative predictive values were performed. Longitudinal data
      analysis was used to detect factors influencing the effectiveness of
      transtelephonic monitoring. The proportion of missed transmissions was
      calculated, thus enabling assessment of compliance. Logistic regression was
      performed to determine predictors of poor compliance. RESULTS: Telephone
      transmission of pacemaker function, as a diagnostic tool, had a sensitivity of
      94.8%, specificity of 99.2%, positive predictive value of 82.1%, and negative
      predictive value of 99.9%. Longitudinal analysis failed to show any significant
      predictors of transmission failure. Compliance with a prescribed transmission
      reached 84.5% in our patient population. Logistic regression analysis failed to
      identify any predictors of noncompliance. CONCLUSION: Values for sensitivity and
      specificity indicate that telephone transmission is a useful diagnostic tool for
      assessing pacemaker function at a distance. Negative predictive value is 99.9%,
      indicating that normal telephone transmissions are very reassuring of normal
      pacemaker function. Telephone transmission is equally successful in all age
      groups, genders, distances from a tertiary referral center, underlying diagnoses,
      pacing modes, and pacemaker models. Compliance with telephone transmission follow
      up was higher in our population than in previous studies.

PMID- 17547604
TI  - Complication risk with pulse generator change: implications when reacting to a
      device advisory or recall.
AB  - BACKGROUND: Recent advisories and recalls of pacemakers and implantable
      cardioverter-defibrillators (ICDs) have highlighted the need for evidence-based
      recommendations regarding management of patients with advisory devices. In order
      to better facilitate decision-making when weighing the relative risks and
      benefits of performing generator changes in these patients, we conducted a review
      to assess operative complication rates. METHODS: We reviewed generator changes
      performed between 2000 and 2005 at the Mayo Clinic-Rochester, including a total
      of 732 change-outs consisting of 570 done for elective replacement indicators
      (ERI) and 162 for manufacturer advisories or recalls. Complications included all
      those requiring reoperation, occurring within a 60-day period postoperatively and
      directly attributable to the generator change. These included infection requiring
      device excision, hematoma requiring evacuation, and incisional dehiscence
      requiring reclosure. RESULTS: Operation-associated complications requiring
      intervention were noted in 9 patients, or 1.24% of our population. Of these nine
      complications, eight occurred among patients receiving pulse generator
      replacement for ERI (1.40%) and one occurred in a patient receiving replacement
      for a manufacturer advisory or recall (0.62%). Complications included 5
      infections, 3 hematomas, and 1 incisional dehiscence. CONCLUSIONS: Generator
      replacement is not a benign procedure and associated risks must be weighed in the
      context of other variables when making management choices in patients with
      advisory or recall devices.

PMID- 17547605
TI  - Electromagnetic Interference (EMI) and arrhythmic events in ICD patients
      undergoing gastrointestinal procedures.
AB  - BACKGROUND: The objective was to determine the effect of electromagnetic
      interference (EMI) in patients undergoing gastrointestinal endoscopy. The
      implantable cardioverter-defibrillator (ICD) is the primary therapeutic modality
      for patients at risk for sudden cardiac death. One potential problem with ICDs is
      interactions with electrical devices and medical procedures causing EMI or
      triggering arrhythmic events. Endoscopy frequently employs electrocautery (EC)
      for diagnosis and treatment of gastrointestinal diseases. Current guidelines
      advise inactivating ICDs before any surgical procedure. There is limited
      information on management of ICDs during endoscopy with or without EC. We
      prospectively evaluated patients with ICDs undergoing endoscopic procedures at
      our institution. METHODS AND RESULTS: Forty-one ICD patients underwent 52
      gastrointestinal endoscopies over 17 months. The mean age of the population was
      66 years (51-83). There were 28 men and 13 women. Thirteen patients had single
      chamber devices, 25 had dual chamber devices, and 2 had biventricular ICDs. The
      mean tachyarrhythmia detection rate programmed was 164.7 bpm (125-188). Eighteen
      procedures (43.9%) required biopsy, coagulation, or polypectomy. Of these, 10
      (55%) required the use of EC. Only unipolar EC with mean current 19.6 mA was
      used. All ICDs were programmed to detection-only with therapies off. Sensitivity
      was left at nominal programmed settings. Post procedure interrogation showed no
      detection of EMI or tachyarrhythmic events. CONCLUSIONS: Our study shows no EMI
      or arrhythmic events triggered during endoscopic procedures in patients with
      pectorally implanted transvenous ICDs. Routine practice of programming ICDs off
      for gastrointestinal procedures may not be necessary. However, larger studies are
      needed before change in current recommendations.

PMID- 17547606
TI  - Single chamber atrial pacing: a realistic option in sinus node disease: a long
      term follow-up study of 213 patients.
AB  - BACKGROUND: Despite several decades of experience with atrial pacing, many
      centers do not apply this mode to any greater extent, mainly because of concerns
      for the development of future atrioventricular (AV) block or atrial fibrillation.
      Recent studies have emphasized possible negative effects of right ventricular
      stimulation, even when AV-synchrony is preserved, and have thus given rise to
      renewed interest in single chamber atrial pacing for sinus node disease. METHODS:
      This study presents the results of up to 19 years' follow-up of 213 patients with
      sinus node disease treated with atrial pacing with respect to survival and causes
      of death, development of atrial fibrillation and AV block, and total mode
      survival. Patients were divided into two groups: with or without associated
      atrial tachyarrhythmias at the time of implant. Results are given for all
      patients and for the two groups separately. RESULTS: The mean follow-up time was
      10.1 years. The survival of the entire group was lower after 10 years than that
      of an age and gender-matched general Swedish population. This was caused by
      patients with the brady-tachy syndrome (BT) having a significantly higher
      mortality rate than controls, whereas those with bradycardia only (B) had
      survival comparable to the general population. Permanent atrial fibrillation (AF)
      developed in 20% of patients and was significantly more common in patients with
      BT. The majority of patients with AF (78%) no longer needed any pacing, i.e., did
      not require ventricular stimulation due to slow ventricular rate. The annual
      incidence of high grade AV block was 1.8%. If patients with preexisting bundle
      branch block were excluded, the incidence was 1.6%. No fatal episode of AV block
      was seen. The overall mode survival at the end of follow-up was 75%, with 155
      patients still with atrial pacemakers. CONCLUSION: Atrial pacing is a safe and
      reliable mode of pacing in patients with sinus node disease, even in the very
      long-term.

PMID- 17547607
TI  - Intramyocardial pacing and sensing for the enhancement of cardiac stimulation and
      sensing specificity.
AB  - BACKGROUND: Intracardiac electrodes create an "antenna" capable of
      unintentionally recording and stimulating tissue beyond the chamber in which they
      are positioned, resulting in far-field R wave oversensing in pacemakers and
      inappropriate detection in defibrillators. This feasibility study sought to
      determine whether a specially constructed lead with two distal totally
      intramyocardial electrodes could overcome these limitations. METHODS: Two mongrel
      dogs were anesthetized and a median sternotomy performed. Epicardial
      intramyocardial pacing and sensing function was assessed and compared to standard
      active fixation pacing and sensing placed at the same atrial and ventricular
      sites. Right ventricular pacing was also assessed. RESULTS: For the novel
      intramyocardial lead, the average R wave amplitude was 7.2 mV, compared to an
      average R wave of 8.4 mV for the standard active fixation lead placed at
      identical ventricular sites; P-waves were also similar. Cross-chamber sensing was
      present in the ventricle and atrium with the standard lead, and absent with the
      intramyocardial lead. The average pacing threshold was 0.7 mA at 0.2 ms for the
      novel lead compared to 1.1 mA for the standard lead. With the standard lead,
      phrenic stimulation was seen at threshold (cathode distal) and at 3 mA (cathode
      proximal electrode). No phrenic stimulation was seen with the novel
      intramyocardial lead despite outputs up to 20 mA at sites located 3-5 mm from the
      phrenic nerve. CONCLUSION: Totally intramyocardial pacing is feasible, and
      results in site-specific pacing and sensing function. This may eliminate far
      field signal oversensing and phrenic stimulation in future devices.

PMID- 17547608
TI  - Alternate site atrial pacing in the young: conventional echocardiography and
      tissue Doppler analysis of the effects on atrial function and ventricular
      filling.
AB  - BACKGROUND: Although the right atrial appendage (RAA) is typically used for
      atrial pacing lead implant, recent studies have shown benefits of alternate site
      atrial pacing (ASAP) in the elderly. However, comparable studies in the young are
      lacking. METHODS: To investigate effects of ASAP on cardiac function and
      atrioventricular mechanical interactions in the young, 26 subjects (ages 10 to 23
      years) with normal cardiac anatomy, function, and atrioventricular node
      conduction underwent echocardiography during electrophysiology studies while in
      sinus rhythm (NSR), and with temporary pacing from high right atrium (HRA), RAA,
      mid septal right atrium approximating Bachmann's bundle (BB), and left atrium
      (LA) via the distal coronary sinus (CS). After a paced steady state of 10
      minutes, left atrial total and systolic ejection fractions, color-guided mitral
      inflow, and annular tissue Doppler indices were obtained. Left ventricular
      ejection fraction and myocardial performance indexes (MPI) were calculated.
      RESULTS: The total and systolic LA ejection fractions were higher during the NSR
      compared to all ASAP. Mitral inflow velocities changed significantly with ASAP.
      The passive/active ventricular filling ratio (E/A) deteriorated from NSR to HRA
      to BB to CS. There were significant changes in late diastolic tissue Doppler
      velocities during ASAP compared to NSR. The MPI during ASAP differed from those
      during the NSR. HRA and Bachmann bundle pacing provided better MPIs than RAA or
      CS pacing. CONCLUSION: The location of atrial pacing leads has an acute impact on
      cardiac function and atrioventricular mechanical interaction. Pacing close to
      sinus node location may be beneficial in the young.

PMID- 17547609
TI  - Bradypacing: indications and management challenges in Nigeria.
AB  - BACKGROUND: Permanent pacemaker implantation is a life-saving procedure that is
      performed worldwide. There is paucity of reports on pacemaker surgery in Nigeria.
      The aims of the study were to determine the indications for pacemaker insertion,
      the demographic distribution of the patients requiring it, the
      electrocardiographic (ECG) changes, and the management challenges in Nigeria.
      MATERIALS AND METHOD: One hundred consecutive patients who had pacemaker
      insertion done by our team from 1999 were included in the study. The patients'
      biodata, indications for pacemaker insertion, ECG changes, and the treatment
      profile were recorded. RESULTS: There was female preponderance (93.0%) among the
      patients studied. Third-degree heart block was the indication in 86.0% of the
      patients and most patients did well with single lead ventricular pacing which is
      generally cheaper than the dual chamber pacing. CONCLUSION: The majority of
      bradyarrhythmia patients in this environment can be maintained on single lead
      ventricular pacemaker.

PMID- 17547610
TI  - Early detection of regional myocardial dysfunction in paced children with
      congenital complete atrioventricular block.
AB  - BACKGROUND: Right ventricular apical pacing leads to global left ventricular
      dysfunction. Assessment of regional myocardial function may allow for earlier
      detection of pacing-induced myocardial remodeling. The aim of this study was to
      evaluate regional myocardial function in paced children with congenital complete
      atrioventricular block (CCAVB). METHODS: We investigated regional myocardial
      function using strain echocardiography and tissue velocity imaging in 10 paced
      children with CCAVB and in 14 age-matched healthy children. Echocardiograms of
      the paced children were obtained during intrinsic junctional rhythm. RESULTS: All
      patients had normal biventricular size and global function. The time from R wave
      to peak regional strain rate and the time from R wave to peak regional myocardial
      tissue velocity were measured in nine segments. The differences between maximum
      and minimum values were used as a measure of contraction delay (dSR and dTV).
      Study group patients had significantly higher dSR and dTV values compared to the
      control group. Mean peak strain rates and peak tissue velocities obtained from
      same segments were significantly decreased in the study group compared to the
      control group. Regional dysfunction was more prominent in the areas of
      ventricular pacing. No significant correlation is found between the duration of
      pacing (2.5-18 years) and dSR, dTV, mean peak strain rates, or mean peak tissue
      velocities. CONCLUSION: Pacing leads to regional myocardial dysfunction that can
      be detected with strain echocardiography and tissue velocity imaging during
      intrinsic junctional rhythm in children with CCAVB. Pacing-induced regional
      myocardial remodeling does not seem to progress with long-term right ventricular
      pacing in children with CCAVB.

PMID- 17547611
TI  - Cardiac autonomic modulation evaluated by heart interval variability is unaltered
      but subtly widespread in the indeterminate Chagas' disease.
AB  - BACKGROUND: Cardiac autonomic function in the indeterminate chronic form of
      Chagas' disease deserves better clearing-up and understanding, since the existing
      findings are scarce and controversial. This work analyzed the short-term heart
      interval variability in order to verify the cardiac autonomic modulation in
      indeterminate Chagas' disease subjects examined in a Brazilian endemic area.
      METHODS: Variability in time and frequency domain of 5-minute electrocardiogram
      (ECG) series of R-R intervals in supine and active standing positions were
      obtained from 18 age-, gender-, body mass index-, lifestyle-, and physical
      activity-matched chagasics and 18 control healthy subjects examined in Agua
      Comprida city, MG, Brazil. Mann-Whitney test was used for analysis of the data
      and spread of the individual indices in both groups. RESULTS: The median of the
      all variability indices in the chagasic group were statistically similar (P= 0.17
      0.87) to that in the control group. A wide dispersion of the almost all
      individual indices values, ranging from normal to variably reduced or increased
      ones, was noted in the majority of the chagasics in relation to the control
      interquartile range, in both postural positions. CONCLUSION: As a group,
      indeterminate Chagas' disease subjects showed unaltered short-term heart interval
      variability. Individual somewhat widespread of majority of time- and frequency
      domain indices, from depressed to exacerbated ones appears to exist. This
      conforms to a variable cardiac autonomic modulation in this form of disease,
      suggesting that the majority of chagasics has no lesions, and a minority has
      subtle lesions of the efferent innervation-sinus node complex.

PMID- 17547612
TI  - Combined ventricular endocardial and epicardial substrate mapping using a
      sonomicrometry-based electroanatomical mapping system.
AB  - BACKGROUND: Substrate mapping using a magnetic electroanatomical mapping system
      (MEAM) has been shown to accurately delineate the location/extent of scarred
      myocardium. This study examined the ability of a sonomicrometry-based
      electroanatomic mapping system (SEAM) to render endocardial and epicardial
      substrate maps of infarcted ventricular myocardium. METHODS AND RESULTS: In 7
      swine with healed myocardial infarctions, combined epicardial and endocardial
      left ventricular (LV) substrate maps were created with both SEAM and MEAM mapping
      systems using 246+/-68 and 244+/-44 points respectively. Scarred myocardium was
      identified based upon bipolar electrogram amplitude < 1.5 mV, and radiofrequency
      ablation lesions were delivered to the scar border as defined by the
      sonomicrometry mapping system. The LV endocardial chamber volume as defined by
      SEAM (125+/-46 ml) correlated well with that defined by the MEAM (137+/-45 ml,
      r=0.77, p < 0.05). The area of infarcted tissue as determined by SEAM was highly
      correlated with that determined by gross pathology (r=0.96 for endocardial scar
      and r=0.92 for epicardial scar p < 0.05). The scar area calculated by the SEAM
      system also correlated well with the scar area determined by the MEAM system
      (0.91 for endocardial scar and 0.90 for epicardial scar p < 0.05). Finally, the
      sonomicrometry-based system was able to guide the placement of radiofrequency
      ablation lesions to the borders of the scar. CONCLUSIONS: This study demonstrates
      that the sonomicrometry-based mapping can accurately reconstruct three
      dimensional voltage maps of the endocardial and epicardial ventricular surfaces
      and guide the placement of ablation lesions along the scar border zone.

PMID- 17547613
TI  - Heart rate turbulence after short runs of nonsustained ventricular tachycardia in
      chronic heart failure.
AB  - BACKGROUND: Heart rate turbulence (HRT) following isolated premature complexes is
      a baroreceptor-mediated prognostic marker. Short runs of spontaneous,
      nonsustained ventricular tachycardia (nsVT) exert a greater hemodynamic effect
      than extrasystoles and may trigger a more potent turbulence-like response
      (HRT(VT)), possibly related to other risk-related markers, such as heart rate
      variability (HRV), left ventricular ejection fraction (EF), and original HRT
      parameters (turbulence slope [TS] and turbulence onset [TO]). METHODS: We studied
      27 patients with heart failure (HF) and nsVT (4-7 beats) on 24-hour Holter
      electrocardiographic recordings (mean age 58 +/- 3.6 years, EF 36%+/- 5.0%).
      Following nsVT, TS(VT) and TO(VT) were measured according to the original
      definitions. HRV, TS, and TO were also assessed. RESULTS: HRT(VT) parameters were
      related to HRV. A significant relation existed between TS(VT) and EF (r= 0.66, P
      < 0.05). HRT(VT) parameters were related to the originally described (TS and TO),
      whereas TO(VT) was higher than TO (1.63 +/- 1.6 vs -1.7 +/- 0.65, P < 0.05).
      CONCLUSIONS: In mild-to-moderate HF, turbulence is observed following short nsVT
      runs and is related to prognostically important HRV indexes and EF. HRT(VT) is
      similar to HRT but TO(VT) is shifted toward more positive values than TO. HRT(VT)
      might be prognostically significant.

PMID- 17547614
TI  - A wide QRS complex tachycardia with different initiation patterns: what is the
      mechanism?
AB  - A 47-year-old man with palpitations underwent electrophysiologic testing (EPS).
      Burst atrial pacing while infusing isoproterenol induced non-reproducible wide
      QRS tachycardias with an unusual pattern of an H-A-V activation with the same
      tachycardia cycle length and two different initiation patterns. The tachycardia
      had the earliest atrial activation at the His bundle region. No dual
      atrioventricular (AV) nodal physiology was demonstrated by programmed atrial
      stimulation. Though a definite diagnosis of AV nodal reentrant tachycardia was
      not obtained, slow pathway ablation was performed in order to avoid inadvertent
      AV block as a complication. Thereafter, no tachycardias were induced by repeat
      burst atrial pacing.

PMID- 17547615
TI  - Sustained ventricular tachycardia in apical hypertrophic cardiomyopathy,
      midcavitary obstruction, and apical aneurysm.
AB  - The prevalence of hypertrophic cardiomyopathy is estimated at 1:500 in the
      general population. Of these patients, approximately 1% develops midcavitary
      obstruction and subsequent apical aneurysm. We present a brief review of the
      literature on apical hypertrophic cardiomyopathy (HCM) using a rare case-based
      example. The etiology for apical aneurysm development is unclear but is thought
      to extend from apical fibrosis and necrosis secondary to subendocardial ischemia.
      The lifetime risk of cardiovascular death in patients with HCM is 2%. However,
      the risk may be higher in patients with apical aneurysms. Definitive therapy
      involves implantation of an automatic implantable cardioverter defibrillator,
      since medical therapy has variable success.

PMID- 17547617
TI  - Acoustic cardiography: validated technology need not be widely applied.

PMID- 17547618
TI  - Visualizing pacemaker-induced phrenic nerve stimulation with acoustic
      cardiography.
AB  - This case study illustrates that acoustic cardiography--a simple non-invasive
      test--can be applied in any diagnostic setting as well as during biventricular
      pacemaker implantation to ensure that the pacemaker settings are not leading to
      phrenic nerve stimulation.

PMID- 17547619
TI  - Focal atrial tachycardia from the fossa ovalis in a patient with Bachmann's
      bundle block.
AB  - We report the case of a patient with tracings during sinus rhythm compatible with
      block of the Bachmann's bundle and presenting with focal atrial tachycardia
      arising from the fossa ovalis with successful ablation on the right side of the
      septum. Upward activation of the left atrium has been related in this case to the
      block of the Bachmann's bundle and to the lack of transseptal conduction.

PMID- 17547620
TI  - Bilateral inferior vena cava: a vascular abnormality encountered during
      electrophysiologic study.
AB  - In the course of clinical practice, the electrophysiologist may encounter a wide
      variety of vascular abnormalities, which are important to recognize, as they may
      potentially impact on the health and welfare of the patient. We describe a case
      of bilateral inferior vena cava and review its etiology, diagnosis, and
      significance to the cardiologist and electrophysiologist.

PMID- 17547621
TI  - Inferior vena cava approach to permanent pacemaker implantation.
AB  - A 89-year-old woman required permanent pacemaker implantation because of
      symptomatic bradyarrhythmia with multiple falls and repeated fractures. Because
      of the obstruction of the thoracic veins and infection of both groins, an
      alternative approach via directly punctured inferior vena cava was performed. At
      follow-up, the patient remained well with an excellent symptomatic response to
      pacing. The method seems simple to perform and is an alternative when the usual
      pectoral implantation site is inaccessible.

PMID- 17547622
TI  - Occurrence of "J waves" in 12-lead ECG as a marker of acute ischemia and their
      cellular basis.
AB  - The "J wave" (also referred to as "the Osborn wave,""the J deflection," or "the
      camel's hump") is a distinctive deflection occurring at the QRS-ST junction. In
      1953, Dr. John Osborn described the "J wave" as an "injury current" resulting in
      ventricular fibrillation during experimental hypothermia. Although "J Wave" is
      supposed to be pathognomonic of hypothermia, it is seen in a host of other
      conditions such as hypercalcemia, brain injury, subarachnoid hemorrhage,
      cardiopulmonary arrest from over sedation, the Brugada syndrome, vasospastic
      angina, and idiopathic ventricular fibrillation. However, there is paucity of
      literature data as regards to ischemic etiology of "J Wave." In this article, we
      present a case where "J waves" were probably induced by ischemia. We also discuss
      the mechanism of ischemia-induced "J wave" accentuation and its prognostic
      implications.

PMID- 17547623
TI  - Cardiac papillary fibroelastoma presenting with recurrent ventricular
      tachycardia.
AB  - A 72-year-old man presented with multiple episodes of pulseless ventricular
      tachycardia, 10 days following an ST-segment elevation myocardial infarction. He
      had a 6-year cardiovascular history that included four neurological events and
      two myocardial infarctions. Transesophageal echocardiography revealed two mobile
      masses on the aortic valve. A transaortic surgical approach was successful in
      removing both masses. Histology confirmed papillary fibroelastoma. The patient
      subsequently received an implantable cardioverter defibrillator.

PMID- 17547624
TI  - Brugada type electrocardiographic changes induced by concomitant use of lithium
      and propafenone in patient with Wolff-Parkinson-White syndrome.
AB  - We report a case of ST elevation in right precordial leads compatible with type 1
      Brugada syndrome following administration of propafenone in a patient with Wolff
      Parkinson-White syndrome who was receiving lithium at concentrations within
      therapeutic levels. The mechanism of the electrocardiogram changes was considered
      to be caused by the two drugs synergistic sodium channel blocking effects.

PMID- 17547625
TI  - Re: Magnetocardiography study on ventricular depolarization-current pattern in
      patients with brugada syndrome and complete right-bundle branch blocks.

PMID- 17547627
TI  - Atrioventricular nodal reentrant tachycardia in the elderly: efficacy and safety
      of radiofrequency catheter ablation.

PMID- 17547628
TI  - Concerning diagnosis and management of pacemaker endocarditis.

PMID- 17547630
TI  - Vaccine protection against feline immunodeficiency virus: setting the challenge.

PMID- 17547632
TI  - Assessment of the hip reduction angle for predicting osteoarthritis of the hip in
      the Labrador Retriever.
AB  - Hip palpation has been used to provide semiquantitative information regarding
      passive joint laxity and susceptibility to hip dysplasia. The purpose of this
      study was to: (1) evaluate the intra- and inter-examiner repeatability of the hip
      reduction angle measured at 4 months of age by three examiners using manual
      goniometry and an electromagnetic tracking system; (2) compare the hip reduction
      angle measured with manual goniometry to the hip reduction angle measured with
      the electromagnetic tracking system; and (3) evaluate the hip reduction angle,
      distraction index and Ortolani manoeuvre at 4 months of age as predictors of the
      development of hip osteoarthritis at 12 months of age in 11 Labrador Retriever
      dogs. Intra- and inter-examiner repeatability was demonstrated for both the
      manual and electromagnetic goniometric measurement of the hip reduction angle
      (coefficient of variation < 4.3% and < 6.1%; and P = 0.163 and P = 0.836
      respectively). The hip reduction angle measured by manual goniometry was
      moderately correlated to the hip reduction angle measured by the electromagnetic
      tracking system (r = 0.603, P < 0.0000). The hip reduction angle measured by
      manual and electromagnetic goniometry was a poor predictor of osteoarthritis at
      12 months of age (r = 0.231, P < 0.062, and r = 0.321, P < 0.01). The distraction
      index was moderately correlated with the development of osteoarthritis by 12
      months of age (r = 0.493, P < 0.0000). The Ortolani sign was sensitive (100%) but
      not specific (41%) for the development of osteoarthritis at 12 months of age. The
      hip reduction angle did not further quantify the Ortolani manoeuvre as a
      predictor of osteoarthritis in Labrador Retrievers.

PMID- 17547633
TI  - Determinants of passive hip range of motion in adult Greyhounds.
AB  - OBJECTIVE: To determine the ranges of normal pelvic limb range of motion in adult
      Greyhound dogs, and to explore which factors influence hip range of motion in a
      population bred to meet the specific demands of racing. Design A cross-sectional
      study design. METHOD: Thirty-two dogs (17 male and 15 female) 13 to 81 months old
      were randomly selected from a local pool of 160 Greyhounds. Goniometric
      measurements of hip, stifle and hock range of motion were recorded in triplicate.
      Signalment information collected included sex, weight and age of each Greyhound.
      The outcome factors for the study were range of hip flexion and hip extension.
      The theorised exposures, age, sex, weight, racing history and hock and stifle
      range of motion, were modelled against the outcome variables by linear regression
      analysis. RESULTS: Male dogs were significantly heavier (P < 0.001) and older (P
      < 0.002) than female dogs. Mean hip flexion was 71.75 degrees and mean hip
      extension 128.10 degrees. The determinants of hip flexion were sex (P = 0.008)
      and range of stifle flexion (P = 0.002). Race training did not influence the
      range of hip flexion in the sample. Determinants of hip extension included range
      of stifle extension (P = 0.015), history of race training (P = 0.004) and hock
      flexion. The mean hip extension of raced Greyhounds was 134.95 degrees compared
      with 121.25 degrees for unraced Greyhounds (mean difference -13.70, 95%
      confidence interval -18.12, -9.29; P < 0.001). CONCLUSIONS: This study has
      reported isolated pelvic limb joint range of motion in the racing Greyhound. Hip
      range of motion was affected by stifle range of motion, sex and race training.
      Dogs that had received race training had greater flexibility, possibly due to
      training having an active stretching role on muscles, tendons and other
      structures limiting the hip range of motion.

PMID- 17547634
TI  - Accuracy of prediction of canine litter size and gestational age with ultrasound.
AB  - Different sonographic criteria have been developed to estimate canine fetal age,
      including fetal mensuration and assessment of fetal organ development. This
      retrospective study assessed the accuracy of gestational age and litter size
      predictions in 76 bitches using one of two techniques. The first method used the
      differential features of fetal organ development that occur in early and mid
      pregnancy, based on published tables for beagles. The second method used
      biparietal head and trunk diameters to predict gestational age based on tables
      published for late gestational Labrador Retrievers. The accuracy of the two
      methods was compared and the effect of maternal body weight and litter size
      evaluated. Litter size and maternal body weight did not affect the accuracy of
      gestational age prediction. Using a combination of both methods, the overall
      accuracy of predicting parturition date within 65 +/- 1 day and +/- 2 days was
      70.8% and 86.1%, respectively. The correct litter size was predicted in 65% of
      cases, and in 89.5% of cases for +/- 1 pup. Pearson's correlation between actual
      litter size and predicted litter size was high (R = 0.957, P < 0.001). The organ
      development method of predicting gestational age was more accurate than late
      gestational fetal mensuration (P = 0.019). The optimum time for sonographic
      estimation of fetal age and litter size is early and mid pregnancy.

PMID- 17547635
TI  - Gall bladder torsion and rupture in a dog.
AB  - A 6-year-old desexed female German Shepherd dog was referred to the Murdoch
      University Veterinary Hospital for assessment and management of acute onset
      vomiting, diarrhoea, polydipsia and lethargy of 2 days duration. Surgical,
      microbiological and histological findings were consistent with necrotising
      cholecystitis secondary to gall bladder torsion, resulting in gall bladder
      rupture and secondary non-septic bile peritonitis. A chronic peritoneopleural
      perforation resulting from an abdominal cavity foreign body and congenital
      peritoneopericardial hernia were also present. The dog made a full recovery
      following cholecystectomy, foreign body removal, repair of the peritoneopleural
      perforation and peritoneopericardial herniorrhaphy. This is the first recorded
      case of gall bladder torsion in the dog.

PMID- 17547636
TI  - A comparison of duck and chicken egg yolk for cryopreservation of stallion sperm.
AB  - OBJECTIVE: Duck and chicken egg yolk were compared for their protective effects
      against cold shock during the cryopreservation of stallion sperm in a lactose
      EDTA-glycerol cryodiluent. DESIGN: A completely randomised design was used.
      Procedure Ejaculates from five stallions (n = 14 ejaculates) were split and
      diluted to either 20 or 200 x 10(6) sperm/mL in a lactose-EDTA extender
      containing either duck or chicken egg yolk. The extended semen was then frozen in
      liquid nitrogen. The percentage of sperm total motility and forward progressive
      motility were assessed before freezing and at 0 and 1 hr after thawing.
      Morphology data were also collected at 0 and 1 hr post thaw. RESULTS: Total and
      forward progressive motility were higher when the sperm were frozen in the
      presence of duck rather than chicken egg yolk. Furthermore, the total and forward
      progressive motility and percentage of morphologically normal sperm were higher
      when frozen at a concentration of 200 than 20 x 10(6)/mL. CONCLUSION: The results
      of this study demonstrate that the motility parameters of stallion sperm are
      improved when the semen is frozen in lactose EDTA extender supplemented with duck
      egg yolk rather than chicken egg yolk. Moreover, sperm motility and the
      percentage of morphologically normal sperm were higher after freezing at a
      concentration of 200 x 10(6)/ml rather than 20 x 10(6)/ml.

PMID- 17547637
TI  - A serological and virological survey for evidence of infection with Newcastle
      disease virus in Australian chicken farms.
AB  - OBJECTIVE: To determine the prevalence and distribution of antibodies to
      Newcastle disease virus on Australian chicken farms and to determine the
      pathotype and relationships of the Newcastle disease viruses present on those
      farms. DESIGN: A cross-sectional survey of 753 commercial chicken farms.
      PROCEDURE: The survey comprised a detailed questionnaire and collection of venous
      blood samples. The titre of antibodies to Newcastle disease virus was determined
      by haemagglutination inhibition. Virus isolation was conducted from cloacal and
      tracheal swabs taken from chickens in serologically positive flocks. Virus
      isolates were pathotyped on the basis of the deduced Fusion protein cleavage site
      determined by nucleotide sequencing of a 265 bp region of the genome in the
      region of the cleavage site. RESULTS: Antibody evidence of Newcastle disease
      virus infection was found on 300 of the 753 surveyed farms throughout all 11
      geographic regions of the survey. The highest prevalence occurred in the Sydney
      basin, New South Wales and Victoria east regions. Antibody titres were also
      highest in the regions where serologically positive flocks were most prevalent.
      The 259 virus isolates revealed nine different RNA sequences. Of the nine virus
      groups isolated, the most common group W was identical in sequence to the V4
      vaccine strain. Five of the other groups had novel RNA sequences in the region of
      the F protein cleavage site. CONCLUSIONS: Antibodies to Newcastle disease virus
      are highly prevalent in the Australian chicken flock but all identified strains
      were avirulent in nature.

PMID- 17547638
TI  - Pooled faecal culture for the detection of Mycobacterium avium subsp
      paratuberculosis in goats.
AB  - OBJECTIVE: To evaluate pooled faecal culture for herd diagnosis of caprine
      Johne's disease and relate these findings to faecal shedding rates of
      Mycobacterium avium subsp paratuberculosis (Map). DESIGN: Radiometric broth
      culture was applied to several pooling dilutions, and shedding rates were
      estimated from a regression equation based on bacterial growth rates and known
      processing losses during radiometric culture. PROCEDURE: Sixteen faecal samples
      from goats naturally infected with sheep (n = 3) or cattle (n = 13) strains of
      Map, were diluted in normal goat faeces from 1 in 5 to 1 in 50. Cultures were
      confirmed by IS900 polymerase chain reaction and restriction endonuclease
      analysis, and mycobactin dependency. The numbers of viable Map in the culture
      inocula were determined by endpoint titration (most probable number) of nine
      samples and related to a cumulative growth index. RESULTS: A pooling dilution of
      1 in 25 with an incubation period of 10 weeks detected 13 of 16 culture positive
      goats, all shedding > or = 2 x 10(4) Map per gram of faeces. Two samples
      containing very low numbers of Map (< 2 x 10(3)/g) were only culture positive
      from undiluted faeces. Thirteen of 16 goats were considered to be shedding low to
      moderate concentrations of Map (< 2 x 10(5)/g faeces). CONCLUSIONS: These data
      support a pooling dilution of 1 in 25 for application of pooled faecal culture as
      a diagnostic tool in caprine Johne's disease control. A test based on this
      dilution would reduce laboratory costs of whole herd testing in goats by
      approximately 40% relative to serology and 75 to 90% relative to individual
      faecal culture.

PMID- 17547640
TI  - Investigation of diseases with an infectious aetiology.

PMID- 17547641
TI  - Neosporosis and hammondiosis in dogs.
AB  - The dog is a definitive host of the protozoan parasite Neospora caninum, and in
      many parts of the world, infection is relatively common as determined by
      serology. Reported seroprevalences usually range from 0 to 20 per cent, however,
      reports of clinically affected dogs are infrequent. Affected dogs are generally
      less than six months old and predominantly have signs of an ascending hindleg
      paralysis, with the associated lesions of polyradiculoneuritis and granulomatous
      polymyositis. Although any organ may be affected, infections are more common in
      the central nervous system, muscles, lungs and skin. Ante-mortem diagnosis is
      difficult but serology and cytology can aid diagnosis. The diagnosis can be
      confirmed by histology, immunohistochemistry, the use of molecular techniques on
      biopsy material, or on post-mortem examination. Neospora caninum oocysts are
      rarely found in faeces and must be differentiated from oocysts of related
      coccidians such as Hammondia heydorni and Toxoplasma gondii. Hammondia heydorni
      can cause diarrrhoea in immunosuppressed dogs. Neosporosis should be suspected in
      young pups with an ascending paralysis of the hindlegs. Treatment with
      clindamycin and potentiated sulphonamides may be useful in cases where muscular
      atrophy and fibrosis are absent. Feeding of raw meat is a potential risk factor
      for infection of dogs and should be discouraged.

PMID- 17547642
TI  - Recurrent supraventricular arrhythmias in a dog with atrial myocarditis and
      gastritis.
AB  - This report describes a dog with recurrent atrial fibrillation and atrial flutter
      associated with chronic gastritis. Although no underlying structural heart
      disease was apparent antemortem or on gross post-mortem examination, chronic
      atrial myocarditis was seen on histopathological examination. Atrial myocarditis
      is a recognised cause of atrial fibrillation in human beings with presumed lone
      fibrillation, and an association between supraventricular tachyarrhythmias and
      infectious agents has been made.

PMID- 17547643
TI  - Providencia stuartii infection in a dog with severe skin ulceration and
      cellulitis.
AB  - The aim of this report is to present a case of severe skin ulceration and
      cellulitis in a seven year old mongrel dog following cystitis. The Providencia
      stuartii strain was the only isolate from skin lesions. This bacterium is a Gram
      negative rod belonging to the family of Enterobacteriaceae. To the best of our
      knowledge, even though there are some reports in the literature concerning animal
      infections with Providencia species, there have been no cases of cellulitis in
      which this pathogen is involved. The Providencia stuartii strain was highly
      sensitive to amikacin, and the dog responded quickly to this antibiotic.

PMID- 17547644
TI  - What is your diagnosis? Nocadia infection.

PMID- 17547647
TI  - Brachyury-downstream notochord genes and convergent extension in Ciona
      intestinalis embryos.
AB  - Formation of the chordate body is accomplished by a complex set of morphogenetic
      movements including convergent extension of notochord cells. In the ascidian
      Ciona intestinalis, Brachyury plays a key role in the formation of the notochord,
      and more than 30 Bra-downstream notochord genes have been identified. In the
      present study, we examined the effects of functional suppression of nine Bra
      downstream notochord genes, which include Ci-PTP, Ci-ACL, Ci-prickle, Ci-netrin,
      Ci-trop, Ci-Noto3, Ci-ASAK, Ci-ERM and Ci-pellino. When the function of the first
      two genes (Ci-PTP and Ci-ACL) was suppressed with specific morpholinos, the
      notochord cells failed to converge, while functional suppression of Ci-prickle
      resulted in a failure of intercalation, and therefore the cells in these three
      types of embryo remained in the mid-dorsal region of the embryo. Functional
      suppression of the next four genes (Ci-netrin, Ci-trop, Ci-Noto3 and Ci-ASAK)
      resulted in the partial defect of intercalation, and the notochord did not
      consist of a single row. In addition, when the function of the last two genes (Ci
      ERM and Ci-pellino) was suppressed, notochord cells failed to elongate in the
      embryo, even though convergence/extension took place normally. These results
      indicate that many Bra-downstream notochord genes are involved in
      convergence/extension of the embryo.

PMID- 17547648
TI  - Regeneration-dependent conditional gene knockdown (Readyknock) in planarian:
      demonstration of requirement for Djsnap-25 expression in the brain for negative
      phototactic behavior.
AB  - Freshwater planarians have a simple and evolutionarily primitive brain structure.
      Here, we identified the Djsnap-25 gene encoding a homolog of the evolutionarily
      conserved synaptic protein SNAP-25 from the planarian Dugesia japonica and
      assessed its role in brain function. Djsnap-25 was expressed widely in the
      nervous system. To investigate the specific role of Djsnap-25 in the brain, we
      developed a unique technique of RNA interference (RNAi), regeneration-dependent
      conditional gene knockdown (Readyknock), exploiting the high regenerative
      capacity of planarians, and succeeded in selectively eliminating the DjSNAP-25
      activity in the head region while leaving the DjSNAP-25 activity in the trunk
      region intact. These knockdown animals showed no effect on brain morphology or on
      undirected movement of the trunk itself. Light-avoidance behavior or negative
      phototaxis was used to quantitatively analyze brain function in the knockdown
      animals. The results suggested that the DjSNAP-25 activity within the head region
      is required for two independent sensory-processing pathways that regulate
      locomotive activity and directional movement downstream of distinct primary
      sensory outputs coming from the head margin and the eyes, respectively, during
      negative phototaxis. Our approach demonstrates that planarians are a powerful
      model organism to study the molecular basis of the brain as an information
      processing center.

PMID- 17547649
TI  - Right-elevated expression of charon is regulated by fluid flow in medaka
      Kupffer's vesicle.
AB  - Recent studies have revealed that a cilium-generated liquid flow in the node has
      a crucial role in the establishment of the left-right (LR) axis in the mouse. In
      fish, Kupffer's vesicle (KV), a teleost-specific spherical organ attached to the
      tail region, is known to have an equivalent role to the mouse node during LR axis
      formation. However, at present, there has been no report of an asymmetric gene
      expressed in KV under the control of fluid flow. Here we report the earliest
      asymmetric gene in teleost KV, medaka charon, and its regulation. Charon is a
      member of the Cerberus/DAN family of proteins, first identified in zebrafish.
      Although zebrafish charon was reported to be symmetrically expressed in KV,
      medaka charon displays asymmetric expression with more intense expression on the
      right side. This asymmetric expression was found to be regulated by KV flow
      because symmetric and up-regulated charon expression was observed in flow
      defective embryos with immotile cilia or disrupted KV. Taken together, medaka
      charon is a reliable gene marker for LR asymmetry in KV and thus, will be useful
      for the analysis of the early steps downstream of the fluid flow.

PMID- 17547650
TI  - Involvement of hydrogen peroxide and nitric oxide in salt resistance in the
      calluses from Populus euphratica.
AB  - Nitric oxide (NO) and hydrogen peroxide (H2O2) function as signalling molecules
      in plants under abiotic and biotic stresses. Calluses from Populus euphratica,
      which show salt tolerance, were used to study the interaction of NO and H2O2 in
      plant adaptation to salt resistance. The nitric oxide synthase (NOS) activity was
      identified in the calluses, and this activity was induced under 150 mM NaCl
      treatment. Under 150 mM NaCl treatment, the sodium (Na) percentage decreased, but
      the potassium (K) percentage and the K/Na ratio increased in P. euphratica
      calluses. Application of glucose/glucose oxidase (G/GO, a H2O2 donor) and sodium
      nitroprusside (SNP, a NO donor) revealed that both H2O2 and NO resulted in
      increased K/Na ratio in a concentration-dependent manner. Diphenylene iodonium
      (DPI, an NADPH oxidase inhibitor) counteracted H2O2 and NO effect by increasing
      the Na percentage, decreasing the K percentage and K/Na ratio. NG-monomethyl-L
      Arg monoacetate (NMMA, an NO synthase inhibitor) and 2-phenyl-4,4,5,5-tetramethyl
      imidazoline-1-oxyl-3-oxyde (PTIO, a specific NO scavenger) only reversed NO
      effect, but did not block H2O2 effect. The increased activity of plasma membrane
      (PM) H+ -ATPase caused by salt stress was reversed by treatment with DPI and
      NMMA. Exogenous H2O2 increased the activity of PM H+ -ATPase, but the effect
      could not be diminished by NMMA and PTIO. The NO-induced increase of PM H+ 
      ATPase can be reversed by NMMA and PTIO, but not by DPI. Western blot analysis
      demonstrated that NO and H2O2 stimulated the expression of PM H+ -ATPase in P.
      euphratica calluses. These results indicate that NO and H2O2 served as
      intermediate molecules in inducing salt resistance in the calluses from P.
      euphratica under slat stress by increasing the K/Na ratio, which was dependent on
      the increased PM H+ -ATPase activity.

PMID- 17547651
TI  - Consequences of insect herbivory on grape fine root systems with different growth
      rates.
AB  - Herbivory tolerance has been linked to plant growth rate where plants with fast
      growth rates are hypothesized to be more tolerant of herbivory than slower
      growing plants. Evidence supporting this theory has been taken primarily from
      observations of aboveground organs but rarely from roots. Grapevines differing in
      overall rates of new root production, were studied in Napa Valley, California
      over two growing seasons in an established vineyard infested with the sucking
      insect, grape phylloxera (Daktulosphaira vitifoliae Fitch). The experimental
      vineyard allowed for the comparison of two root systems that differed in rates of
      new root tip production (a 'fast grower', Vitis berlandieri x Vitis rupestris cv.
      1103P, and a slower-growing stock, Vitis riparia x Vitis rupestris cv. 101-14
      Mgt). Each root system was grafted with a genetically identical shoot system
      (Vitis vinifera cv. Merlot). Using minirhizotrons, we did not observe any
      evidence of spatial or temporal avoidance of insect populations by root growth.
      Insect infestations were abundant throughout the soil profile, and seasonal peaks
      in phylloxera populations generally closely followed peaks in new root
      production. Our data supported the hypothesis that insect infestation was
      proportional to the number of growing tips, as indicated by similar per cent
      infestation in spite of a threefold difference in root tip production. In
      addition, infested roots of the fast-growing rootstock exhibited somewhat shorter
      median lifespans (60 d) than the slower-growing rootstock (85 d). Lifespans of
      uninfested roots were similar for the two rootstocks (200 d). As a consequence of
      greater root mortality of younger roots, infested root populations in the fast
      growing rootstock had an older age structure. While there does not seem to be a
      trade-off between potential growth rate and relative rate of root infestation in
      these cultivars, our study indicates that a fast-growing root system may more
      readily shed infested roots that are presumably less effective in water and
      nutrient uptake. Thus, differences in root tip production may be linked to
      differences in the way plants cope with roots that are infested by sucking
      insects.

PMID- 17547652
TI  - Interaction of nitrogen nutrition and salinity in Grey poplar (Populus tremula x
      alba).
AB  - Salinity represents an increasing environmental problem in managed ecosystems.
      Populus spp. is widely used for wood production by short-rotation forestry in
      fertilized plantations and can be grown on saline soil. Because N fertilization
      plays an important role in salt tolerance, we analysed Grey poplar (Populus
      tremula x alba, syn. Populus canescens) grown with either 1 mM nitrate or
      ammonium subjected to moderate 75 mM NaCl. The impact of N nutrition on
      amelioration of salt tolerance was analysed on different levels of N metabolism
      such as N uptake, assimilation and N (total N, proteins and amino compounds)
      accumulation. Na concentration increased in all tissues over time of salt
      exposure. The N nutrition-dependent effects of salt exposure were more intensive
      in roots than in leaves. Application of salt reduced root increment as well as
      stem height increase and, at the same time, increased the concentration of total
      amino compounds more intensively in roots of ammonium-fed plants. In leaves, salt
      treatment increased concentrations of total N more intensively in nitrate-fed
      plants and concentrations of amino compounds independently of N nutrition. The
      major changes in N metabolism of Grey poplar exposed to moderate salt
      concentrations were detected in the significant increase of amino acid
      concentrations. The present results indicate that N metabolism of Grey poplar
      exposed to salt performed better when the plants were fed with nitrate instead of
      ammonium as sole N source. Therefore, nitrate fertilization of poplar plantations
      grown on saline soil should be preferred.

PMID- 17547653
TI  - Timing of cotyledon damage affects growth and flowering in mature plants.
AB  - Although the effects of herbivory on plant fitness are strongly linked to age, we
      understand little about how the timing of herbivory at the seedling stage affects
      growth and reproduction for plants that survive attack. In this study, we
      subjected six north-western European, dicotyledonous grassland species (Leontodon
      autumnalis, Leontodon hispidus, Plantago lanceolata, Plantago major, Trifolium
      pratense and Trifolium repens) to cotyledon removal at 7, 14 and 21 d old. We
      monitored subsequent growth and flowering (number of inflorescences recorded, and
      time taken for first flowers to open) over a 107 d period. Cotyledon removal
      reduced growth during establishment (35 d) for all species, and a further three
      exhibited reduced growth at maturity. Four species developed fewer
      inflorescences, or had delayed flowering after cotyledon removal. Although early
      damage (7 d old) had the greatest long-term effect on plant performance,
      responses varied according to the age at which the damage occurred and the
      species involved. Our results illustrate how growth and flowering into the mature
      phase is affected by cotyledon damage during different stages of seedling
      ontogeny, and we highlight the ways in which ontogenetic variation in seedling
      tolerance of tissue loss might impact upon plant fitness in mature plant
      communities.

PMID- 17547654
TI  - Does growth irradiance affect temperature dependence and thermal acclimation of
      leaf respiration? Insights from a Mediterranean tree with long-lived leaves.
AB  - Understanding the response of leaf respiration (R) to changes in irradiance and
      temperature is a prerequisite for predicting the impacts of climate change on
      plant function and future atmospheric CO2 concentrations. Little is known,
      however, about the interactive effects of irradiance and temperature on leaf R.
      We investigated whether growth irradiance affects the temperature response of
      leaf R in darkness (Rdark) and in light (Rlight) in seedlings of a broad-leaved
      evergreen species, Quercus ilex. Two hypotheses concerning Rdark were tested: (1)
      the Q10 (i.e. the proportional increase in R per 10 degrees C rise in
      temperature) of leaf Rdark is lower in shaded plants than in high-light-grown
      plants, and (2) shade-grown plants exhibit a lower degree of thermal acclimation
      of Rdark than plants exposed to higher growth irradiance. We also assessed
      whether light inhibition of Rlight differs between leaves exposed to contrasting
      temperatures and growth irradiances, and whether the degree of thermal
      acclimation of Rlight is dependent on growth irradiance. We showed that while
      growth irradiance did impact on photosynthesis, it had no effect on the Q10 of
      leaf Rdark. Growth irradiance had little impact on thermal acclimation when fully
      expanded, pre-existing leaves were exposed to contrasting temperatures for
      several weeks. When Rlight was measured at a common irradiance, Rlight/Rdark
      ratios were higher in shaded plants due to homeostasis of Rlight between growth
      irradiance treatments and to the lower Rdark in shaded leaves. We also showed
      that Rlight does not acclimate to the same degree as Rdark, and that Rlight/Rdark
      decreases with increasing measuring and growth temperatures, irrespective of the
      growth irradiance. Collectively, we raised the possibility that predictive carbon
      cycle models can assume that growth irradiance and photosynthesis do not affect
      the temperature sensitivity of leaf Rdark of long-lived evergreen leaves, thus
      simplifying incorporation of leaf R into such models.

PMID- 17547655
TI  - Intercellular communication in plants: evidence for two rapidly transmitted
      systemic signals generated in response to electromagnetic field stimulation in
      tomato.
AB  - Exposing all of a wild-type tomato plant to electromagnetic radiation evoked
      rapid and substantial accumulation of basic leucine-zipper transcription factor
      (bZIP) mRNA in the terminal leaf (#4) with kinetics very similar to that seen in
      response to wounding, while in the abscisic acid (ABA) mutant (Sitiens), the
      response was more rapid, but transient. Submitting just the oldest leaf (#1) of a
      wild-type plant to irradiation evoked bZIP mRNA accumulation both locally in the
      exposed leaf and systemically in the unexposed (distant) leaf #4, although
      systemic accumulation was delayed somewhat. Accumulation of Pin2 mRNA was less
      than bZIP in both the exposed and distant leaves in wild type, but there was no
      delay in the systemic response. In Sitiens, bZIP mRNA accumulation was far less
      than in wild type in both local and distant leaves, while Pin2 mRNA accumulation
      was stronger in the exposed leaf, but totally prevented in the systemic leaf. In
      the jasmonic acid (JA) mutant (JL-5) and in wild-type plants treated with the ABA
      biosynthesis inhibitor, naproxen, responses were similar to those in the ABA
      mutant, while treatment of the exposed leaf with calcium antagonists totally
      abolished both local and systemic increases in bZIP transcript accumulation.

PMID- 17547656
TI  - During measurements of root hydraulics with pressure probes, the contribution of
      unstirred layers is minimized in the pressure relaxation mode: comparison with
      pressure clamp and high-pressure flowmeter.
AB  - The effects of unstirred layers (USLs) at the endodermis of roots of young maize
      plants (Zea mays L.) were quantified, when measuring the water permeability of
      roots using a root pressure probe (RPP) in the pressure relaxation (PR) and
      pressure clamp (PC) modes. Different from PRs, PCs were performed by applying a
      constant pressure for certain periods of time. Experimental data were compared
      with results from simulations based on a convection versus diffusion (C/D) model,
      with the endodermis being the main barrier for solutes and water. Solute profiles
      in the stele were calculated as they occurred during rapid water flows across the
      root. The model quantitatively predicted the experimental finding of two distinct
      phases during PRs, in terms of a build-up of concentration profiles in the stele
      between endodermis and xylem vessels. It also predicted that, following a PC,
      half-times (T1/2) of PRs increased as the time used for clamping (and the build
      up of USLs) increased. Following PCs of durations of 15, 30 and 60 s, T1/2
      increased by factors of between 2.5 and 7.0, and water permeability of roots
      (root hydraulic conductivity, Lpr) was reduced by the same factors. When root
      pressure was immediately taken back to the original equilibrium root pressure
      following a PC, there was a transient uptake of water into the root stele
      (transient increase of root pressure), and the size of transients rose with time
      of clamping, as predicted by the model. The results indicated that the 'real'
      hydraulic conductivity of roots should be measured during initial water flows,
      such as during the rapid phase of PRs, when the effect of USLs was minimized. It
      was discussed that 'pressure-propagation effects' could not explain the finding
      of two phases during PRs. The results of USL effects threw some doubt on the use
      of PC and high-pressure flowmeter (HPFM) techniques with roots, where rigorous
      estimates of USLs were still missing despite the fact that large quantities of
      water were forced across the root.

PMID- 17547657
TI  - Comparison between gradient-dependent hydraulic conductivities of roots using the
      root pressure probe: the role of pressure propagations and implications for the
      relative roles of parallel radial pathways.
AB  - Hydrostatic pressure relaxations with the root pressure probe are commonly used
      for measuring the hydraulic conductivity (Lp(r)) of roots. We compared the Lp(r)
      of roots from species with different root hydraulic properties (Lupinus
      angustifolius L. 'Merrit', Lupinus luteus L. 'Wodjil', Triticum aestivum L.
      'Kulin' and Zea mays L. 'Pacific DK 477') using pressure relaxations, a pressure
      clamp and osmotic gradients to induce water flow across the root. Only the
      pressure clamp measures water flow under steady-state conditions. Lp(r)
      determined by pressure relaxations was two- to threefold greater than Lp(r) from
      pressure clamps and was independent of the direction of water flow. Lp(r)
      (pressure clamp) was two- to fourfold higher than for Lp(r) (osmotic) for all
      species except Triticum aestivum where Lp(r) (pressure clamp) and Lp(r) (osmotic)
      were not significantly different. A novel technique was developed to measure the
      propagation of pressure through roots to investigate the cause of the differences
      in Lp(r). Root segments were connected between two pressure probes so that when
      root pressure (P(r)) was manipulated by one probe, the other probe recorded
      changes in P(r). Pressure relaxations did not induce the expected kinetics in
      pressure in the probe at the other end of the root when axial hydraulic
      conductance, and probe and root capacitances were accounted for. An electric
      circuit model of the root was constructed that included an additional capacitance
      in the root loaded by a series of resistances. This accounted for the double
      exponential kinetics for intact roots in pressure relaxation experiments as well
      as the reduced response observed with the double probe experiments. Although
      there were potential errors with all the techniques, we considered that the
      measurement of Lp(r) using the pressure clamp was the most unambiguous for small
      pressure changes, and provided that sufficient time was allowed for pressure
      propagation through the root. The differences in Lp(r) from different methods of
      measurement have implications for the models describing water transport through
      roots and the potential role of aquaporins.

PMID- 17547658
TI  - Compatible solutes reduce ROS-induced potassium efflux in Arabidopsis roots.
AB  - Reactive oxygen species (ROS) are known to be primarily responsible for the
      impairment of cellular function under numerous abiotic and biotic stress
      conditions. In this paper, using non-invasive microelectrode ion flux measuring
      (MIFE) system, we show that the application of a hydroxyl radical (OH*)
      generating Cu2+/ascorbate (Cu/a) mixture to Arabidopsis roots results in a
      massive, dose-dependent efflux of K+ from epidermal cells in the elongation zone.
      Pharmacological experiments suggest that both outward-rectifying K+ channels and
      non-selective cation channels (NSCCs) mediate such effluxes. Low (5 mM)
      concentrations of compatible solutes (glycine betaine, proline, mannitol,
      trehalose or myo-inositol) significantly reduces OH*-induced K+ efflux, similar
      to our previous reports for NaCl-induced K+ efflux. Importantly, a significant
      reduction in K+ efflux was found using osmolytes with no reported free radical
      scavenging activity, as well as those for which a role in free radical scavenging
      has been demonstrated. This indicates that compatible solutes must play other
      (regulatory) roles, in addition to free radical scavenging, in mitigating the
      damaging effects of oxidative stress.

PMID- 17547659
TI  - A potato carboxypeptidase inhibitor gene provides pathogen resistance in
      transgenic rice.
AB  - A defensive role against insect attack has been traditionally attributed to plant
      protease inhibitors. Here, evidence is described of the potential of a plant
      protease inhibitor, the potato carboxypeptidase inhibitor (PCI), to provide
      resistance to fungal pathogens when expressed in rice as a heterologous protein.
      It is shown that rice plants constitutively expressing the pci gene exhibit
      resistance against the economically important pathogens Magnaporthe oryzae and
      Fusarium verticillioides. A M. oryzae carboxypeptidase was purified by affinity
      chromatography and further characterized by mass spectrometry. This fungal
      carboxypeptidase was found to be a novel carboxypeptidase B which was fully
      inhibited by PCI. Overall, the results indicate that PCI exerts its antifungal
      activity through the inhibition of this particular fungal carboxypeptidase B.
      Although pci confers protection against fungal pathogens in transgenic rice, a
      significant cost in insect resistance is observed. Thus, the weight gain of
      larvae of the specialist insect Chilo suppressalis (striped stem borer) and the
      polyphagous insect Spodoptera littoralis (Egyptian cotton worm) fed on pci rice
      is significantly larger than that of insects fed on wild-type plants. Homology
      based modelling revealed structural similarities between the predicted structure
      of the M. oryzae carboxypeptidase B and the crystal structure of insect
      carboxypeptidases, indicating that PCI may function not only as an inhibitor of
      fungal carboxypeptidases, but also as an inhibitor of insect carboxypeptidases.
      The potential impact of the pci gene in terms of protection against fungal and
      insect diseases is discussed.

PMID- 17547660
TI  - Resolving methane fluxes.

PMID- 17547661
TI  - Interactions between abscisic acid, hydrogen peroxide and nitric oxide mediate
      survival responses during water stress.

PMID- 17547662
TI  - Transcriptional or post-transcriptional regulation - how does a plant know when
      to senesce?

PMID- 17547663
TI  - Environmental change and carbon limitation in trees: a biochemical,
      ecophysiological and ecosystem appraisal.
AB  - As C(3) photosynthesis is not yet CO(2)-saturated, forests offer the possibility
      of enhanced growth and carbon (C) sequestration with rising atmospheric CO(2).
      However, at an ecosystem scale, increased photosynthetic rates are not always
      translated into faster tree growth, and in free air carbon enrichment (FACE)
      experiments with trees, the stimulation in above-ground growth often declines
      with time. So is tree growth C-limited? The evidence is reviewed here at three
      different scales. First, at the biochemical scale, the role of Rubisco is
      discussed by considering its evolution and role as a nitrogen (N) storage
      protein. Second, at the ecophysiological scale, C allocation to gain nutrients
      from the soil is considered and it is argued that any C limitation is only
      through a limitation to soil nutrient cycling. Finally, the response of forest
      ecosystems to rising atmospheric CO(2) concentrations is considered and evidence
      from FACE experiments is discussed. From the three lines of evidence we conclude
      that the growth of trees is not C-limited, with the key to understanding future
      responses to climate change being turnover of soil organic matter and nutrient
      cycling.

PMID- 17547664
TI  - No evidence for substantial aerobic methane emission by terrestrial plants: a 13C
      labelling approach.
AB  - * The results of a single publication stating that terrestrial plants emit
      methane has sparked a discussion in several scientific journals, but an
      independent test has not yet been performed. * Here it is shown, with the use of
      the stable isotope (13)C and a laser-based measuring technique, that there is no
      evidence for substantial aerobic methane emission by terrestrial plants,
      maximally 0.3% (0.4 ng g(-1) h(-1)) of the previously published values. * Data
      presented here indicate that the contribution of terrestrial plants to global
      methane emission is very small at best. * Therefore, a revision of carbon
      sequestration accounting practices based on the earlier reported contribution of
      methane from terrestrial vegetation is redundant.

PMID- 17547665
TI  - Nitric oxide induced by hydrogen peroxide mediates abscisic acid-induced
      activation of the mitogen-activated protein kinase cascade involved in
      antioxidant defense in maize leaves.
AB  - * The role of nitric oxide (NO) and the relationship between NO, hydrogen
      peroxide (H(2)O(2)) and mitogen-activated protein kinase (MAPK) in abscisic acid
      (ABA)-induced antioxidant defense in leaves of maize (Zea mays) plants were
      investigated. * Both ABA and H(2)O(2) induced increases in the generation of NO
      in mesophyll cells of maize leaves, and H(2)O(2) was required for the ABA-induced
      generation of NO. Pretreatment with NO scavenger and nitric oxide synthase (NOS)
      inhibitor substantially reduced the ABA-induced production of NO, and partly
      blocked the activation of a 46 kDa MAPK and the expression and the activities of
      several antioxidant enzymes induced by ABA. Treatment with the NO donor sodium
      nitroprusside (SNP) also induced the activation of the MAPK, and enhanced the
      antioxidant defense systems. * Conversely, SNP treatment did not induce the
      production of H(2)O(2), and pretreatments with NO scavenger and NOS inhibitor did
      not affect ABA-induced H(2)O(2) production. * Our results suggest that ABA
      induced H(2)O(2) production mediates NO generation, which, in turn, activates
      MAPK and results in the upregulation in the expression and the activities of
      antioxidant enzymes in ABA signaling.

PMID- 17547666
TI  - Plant Cd2+ and Zn2+ status effects on root and shoot heavy metal accumulation in
      Thlaspi caerulescens.
AB  - * In this study we address the impact of changes in plant heavy metal, (i.e. zinc
      (Zn) and cadmium (Cd)) status on metal accumulation in the Zn/Cd
      hyperaccumulator, Thlaspi caerulescens. * Thlaspi caerulescens plants were grown
      hydroponically on both high and low Zn and Cd regimes and whole-shoot and -root
      metal accumulation, and root (109)Cd(2+) influx were determined. * High-Zn-grown
      (500 microm Zn) plants were found to be more Cd-tolerant than plants grown in
      standard Zn conditions (1 microm Zn). Furthermore, shoot Cd accumulation was
      significantly greater in the high-Zn-grown plants. A positive correlation was
      also found between shoot Zn accumulation and increased plant Cd status.
      Radiotracer (109)Cd root flux experiments demonstrated that high-Zn-grown plants
      maintained significantly higher root Cd(2+) influx than plants grown on 1 microm
      Zn. It was also found that both nickel (Ni) and copper (Cu) shoot accumulation
      were stimulated by high plant Zn status, while manganese (Mn) accumulation was
      not affected. * A speculative model is presented to explain these findings,
      suggesting that xylem loading may be one of the key sites responsible for the
      hyperaccumulation of Zn and Cd accumulation in Thlaspi caerulescens.

PMID- 17547667
TI  - Adaptation of tree growth to elevated CO2: quantitative trait loci for biomass in
      Populus.
AB  - * Information on the genetic variation of plant response to elevated CO(2)
      (e[CO(2)]) is needed to understand plant adaptation and to pinpoint likely
      evolutionary response to future high atmospheric CO(2) concentrations. * Here,
      quantitative trait loci (QTL) for above- and below-ground tree growth were
      determined in a pedigree - an F(2) hybrid of poplar (Populus trichocarpa and
      Populus deltoides), following season-long exposure to either current day ambient
      CO(2) (a[CO(2)]) or e[CO(2)] at 600 microl l(-1), and genotype by environment
      interactions investigated. * In the F(2) generation, both above- and below-ground
      growth showed a significant increase in e[CO(2)]. Three areas of the genome on
      linkage groups I, IX and XII were identified as important in determining above
      ground growth response to e[CO(2)], while an additional three areas of the genome
      on linkage groups IV, XVI and XIX appeared important in determining root growth
      response to e[CO(2)]. * These results quantify and identify genetic variation in
      response to e[CO(2)] and provide an insight into genomic response to the changing
      environment.

PMID- 17547668
TI  - When is breeding for drought tolerance optimal if drought is random?
AB  - * Increasing climatic unpredictability associated with characteristics of some
      species makes plant drought-tolerance an important drought-adaptation strategy.
      Using norm-of-reaction functions, or empirically determined functions that enable
      us to predict the state of a trait given the state of an environmental variable,
      allows modelling of plant performance when water availability varies randomly. *
      A mathematical model is proposed to evaluate drought-tolerance and growth
      strategies given a set of environmental parameters: the frequency of rainy days,
      the soil water-storage capacity, plant water use and plant growth rates. This
      model compares the performance of genotypes that differ in drought tolerance
      expressed as the ability to grow in drier soils, and assumes a general trade-off
      function between drought tolerance and maximum plant growth rate. * It is worth
      selecting plants with a greater degree of drought tolerance, expressed by the
      ability to grow in drier soils whenever the frequency of rains is smaller than
      the rate of soil water depletion. Otherwise, maximizing growth rate at the
      expense of drought tolerance is the best strategy. The nature of the trade-off
      between drought tolerance and plant growth rate also constrains the selection for
      optimal drought-adapted genotypes. * Breeders will have to consider these aspects
      of plant-environment interactions before establishing selection programs for
      drought adaptation.

PMID- 17547669
TI  - Photosynthetic limitations in response to water stress and recovery in
      Mediterranean plants with different growth forms.
AB  - * Whether photosynthesis is limited during water stress and recovery because of
      diffusive or biochemical factors is still open to debate, and apparent
      contradictions appear when various studies on species with different growth forms
      are compared. * Ten Mediterranean species, representing different growth forms,
      were subjected to different levels of water stress, the most severe followed by
      rewatering. A quantitative limitation analysis was applied to estimate the
      effects of water stress on stomatal (S(L)), mesophyll conductance (MC(L)) and
      biochemical limitations (B(L)). * Results confirmed a general pattern of
      photosynthetic response to water stress among C(3) plants when stomatal
      conductance (g(s)) is used as a reference parameter. As g(s) values decreased
      from a maximum to approx. 0.05 mol H(2)O m(-2) s(-1), the total photosynthetic
      limitation rose from 0 to approx. 70%, and this was caused by a progressive
      increase of both S(L) and MC(L) limitations, while B(L) remained negligible. When
      lower values of g(s) were achieved (total photosynthetic limitation increased
      from 70 to 100%), the contribution of S(L) declined, while MC(L) still increased
      and B(L) contributed significantly (20-50%) to the total limitation. *
      Photosynthetic recovery of severely stressed plants after rewatering showed a
      dominant role of MC(L), irrespective of the degree of photosynthesis recovery.

PMID- 17547670
TI  - Simple equations to estimate light interception by isolated trees from canopy
      structure features: assessment with three-dimensional digitized apple trees.
AB  - * Simple models of light interception are useful to identify the key structural
      parameters involved in light capture. We developed such models for isolated trees
      and tested them with virtual experiments. Light interception was decomposed into
      the projection of the crown envelope and the crown porosity. The latter was
      related to tree structure parameters. * Virtual experiments were conducted with
      three-dimensional (3-D) digitized apple trees grown in Lebanon and Switzerland,
      with different cultivars and training. The digitized trees allowed actual values
      of canopy structure (total leaf area, crown volume, foliage inclination angle,
      variance of leaf area density) and light interception properties (projected leaf
      area, silhouette to total area ratio, porosity, dispersion parameters) to be
      computed, and relationships between structure and interception variables to be
      derived. * The projected envelope area was related to crown volume with a power
      function of exponent 2/3. Crown porosity was a negative exponential function of
      mean optical density, that is, the ratio between total leaf area and the
      projected envelope area. The leaf dispersion parameter was a negative linear
      function of the relative variance of leaf area density in the crown volume. * The
      resulting models were expressed as two single equations. After calibration, model
      outputs were very close to values computed from the 3-D digitized databases.

PMID- 17547671
TI  - Functional ecology of ecotypic differentiation in the Californian serpentine
      sunflower (Helianthus exilis).
AB  - * Here, we examined phenotypic differences between locally adapted serpentine and
      riparian populations of the serpentine sunflower Helianthus exilis from northern
      California, USA. * Within a common environment, plants from serpentine and
      riparian sites were grown in regular potting soil or serpentine soil. Physiology,
      morphology, phenology and fitness-related traits were measured. * Overall,
      riparian plants grew more rapidly, attained a larger final size, produced larger
      leaves, and smaller flowering heads. Riparian plants also invested less in root
      biomass and were more water-use-efficient than the serpentine plants. Serpentine
      and riparian plants also differed in leaf concentrations of boron, magnesium,
      sodium and molybdenum. * These ecotypic differences suggest contrasting adaptive
      strategies to cope with either edaphic stress in serpentine sites or intense
      above-ground competition at riparian sites. There was a significant population
      origin x soil type crossing interaction in one fitness trait (average dry weight)
      that mirrored local adaptation previously documented for these riparian and
      serpentine ecotypes. However, because all other fitness traits did not exhibit
      this crossing interaction in our common garden study, it is possible that
      phenotypic differences underlying local adaptation may be amplified in the field
      as a result of biotic and abiotic interactions.

PMID- 17547672
TI  - Changes in photosynthetic metabolism induced by tobamovirus infection in
      Nicotiana benthamiana studied in vivo by thermoluminescence.
AB  - * In thylakoids from Nicotiana benthamiana infected with the pepper mild mottle
      virus (PMMoV), a decreased amount of the PsbP and PsbQ proteins of photosystem II
      and different proteins of the Calvin cycle have been previously observed. We used
      thermoluminescence to study the consequences in vivo. * Measurements on unfrozen
      discs from symptomatic and asymptomatic leaves of plants infected by two
      tobamovirus PMMoV-S and PMMoV-I strains were compared with homologous samples in
      control plants. * Thermoluminescence emission did not reveal noticeable
      alteration of PSII electron transfer activity in infected symptomatic leaves. In
      these leaves, the relative intensity of the 'afterglow' emission indicated an
      increase of the NADPH + ATP assimilatory potential, contrasting with its decrease
      in asymptomatic leaves. High-temperature thermoluminescence, as a result of
      peroxides, increased in symptomatic and asymptomatic leaves. * In young infected
      leaves, PSII activity is preserved, producing a high assimilatory potential.
      Older asymptomatic leaves export more nutrients towards young infected leaves.
      This depresses their assimilatory potential and weakens their defence mechanisms
      against reactive oxygen species, resulting in higher peroxide content.

PMID- 17547673
TI  - Plant signalling components EDS1 and SGT1 enhance disease caused by the
      necrotrophic pathogen Botrytis cinerea.
AB  - * Botrytis cinerea is a necrotrophic fungus that causes grey mould on a wide
      range of food plants, especially grapevine, tomato, soft fruits and vegetables.
      This disease brings about important economic losses in both pre- and postharvest
      crops. Successful protection of host plants against this pathogen is severely
      hampered by a lack of resistance genes in the hosts and the considerable
      phenotypic diversity of the fungus. * The aim of this study was to test whether
      B. cinerea manipulates the immunity-signalling pathways in plants to restore its
      disease. * We showed that B. cinerea caused disease in Nicotiana benthamiana
      through the activation of two plant signalling genes, EDS1 and SGT1, which have
      been shown to be essential for resistance against biotrophic pathogens; and more
      interestingly, virus-induced gene silencing of these two plant signalling
      components enhanced N. benthamiana resistance to B. cinerea. Finally, plants
      expressing the baculovirus antiapoptotic protein p35 were more resistant to this
      necrotrophic pathogen than wild-type plants. * This work highlights a new
      strategy used by B. cinerea to establish disease. This information is important
      for the design of strategies to improve plant pathogen resistance.

PMID- 17547674
TI  - Rhodococcus fascians infection accelerates progression of tobacco BY-2 cells into
      mitosis through rapid changes in plant gene expression.
AB  - * To characterize plant cell cycle activation following Rhodococcus fascians
      infection, bacterial impact on cell cycle progression of tobacco BY-2 cells was
      investigated. * S-phase-synchronized BY-2 cells were cocultivated with R.
      fascians and cell cycle progression was monitored by measuring mitotic index,
      cell cycle gene expression and flow cytometry parameters. Cell cycle alteration
      was further investigated by cDNA-AFLP (amplified fragment length polymorphism). *
      It was shown that cell cycle progression of BY-2 cells was accelerated only upon
      infection with bacteria whose virulence gene expression was induced by a leafy
      gall extract. Thirty-eight BY-2 genes showed a differential expression within 6 h
      post-infection. Among these, seven were previously associated with specific plant
      cell cycle phases (in particular S and G2/M phases). Several genes also showed a
      differential expression during leafy gall formation. * R. fascians-infected BY-2
      cells provide a simple model to identify plant genes related to leafy gall
      development. R. fascians can also be regarded as a useful biotic agent to alter
      cell cycle progression and, thereby, gain a better understanding of cell cycle
      regulation in plants.

PMID- 17547675
TI  - How does a symbiotic fungus modulate expression of its host-plant nitrite
      reductase?
AB  - * In the mycorrhizal association, changes in the metabolic activities expressed
      by the plant and fungal partners could result from modulations in the quantity
      and nature of nutrients available at the plant-fungus interface. This hypothesis
      was tested for the nitrite reductase gene in the association Hebeloma
      cylindrosporumxPinus pinaster. * Transcripts from plant and fungal nitrite
      reductases and a fungal ammonium transporter were quantified in control
      uninoculated roots, extraradical mycelia and mycorrhizas formed by either wild
      type or nitrate reductase deficient fungal strains. * The fungal genes were
      downregulated in mycorrhizas compared with extraradical hyphae. The plant nitrite
      reductase was induced only transiently by NO(3)(-) in the association with a wild
      type strain, but permanently expressed at a high level in mycorrhizas formed by
      the deficient mutant. * These results suggest that reduced nitrogen compounds
      transferred from the fungus to the root cortical cells repress the plant nitrite
      reductase, thus highlighting a plant gene regulation by the nutrients available
      in the Hartig net.

PMID- 17547676
TI  - Wide geographical and ecological distribution of nitrogen and carbon gains from
      fungi in pyroloids and monotropoids (Ericaceae) and in orchids.
AB  - * Stable isotope abundance analyses recently revealed that some European green
      orchids and pyroloids (Ericaceae) are partially myco-heterotrophic, exploiting
      mycorrhizal fungi for organic carbon and nitrogen. Here we investigate related
      species to assess their nutritional mode across various forest and climate types
      in Germany and California. * C- and N-isotope signatures of five green pyroloids,
      three green orchids and several obligate myco-heterotrophic species (including
      the putatively fully myco-heterotrophic Pyrola aphylla) were analysed to quantify
      the green plants' nutrient gain from their fungal partners and to investigate the
      constancy of enrichment in (13)C and (15)N of fully myco-heterotrophic plants
      from diverse taxa and locations relative to neighbouring autotrophic plants. *
      All green pyroloid and one orchid species showed significant (15)N enrichment,
      confirming incorporation of fungi-derived N compounds while heterotrophic C gain
      was detected only under low irradiance in Orthilia secunda. Pyrola aphylla had an
      isotope signature equivalent to those of fully myco-heterotrophic plants. * It is
      demonstrated that primarily N gain from mycorrhizal fungi occurred in all
      taxonomic groups investigated across a wide range of geographical and ecological
      contexts. The (13)C and (15)N enrichment of obligate myco-heterotrophic plants
      relative to accompanying autotrophic plants turned out as a fairly constant
      parameter.

PMID- 17547677
TI  - Specialist and generalist herbivores exert opposing selection on a chemical
      defense.
AB  - * Plant defense traits often show high levels of genetic variation, despite clear
      impacts on plant fitness. This variation may be partly maintained by trade-offs
      in the defense against multiple herbivore species, for example between
      generalists and coevolved specialists. Despite a long-standing discussion in the
      literature on the subject, no study to date has specifically manipulated
      specialist and generalist herbivores independently of one another to determine
      whether the two guilds exert opposing selection pressures on specific defensive
      traits. * In two separate experiments, the dominant specialist and generalist
      herbivores of Brassica nigra were independently manipulated to test whether the
      composition of the herbivore community altered the direction of selection on a
      major defensive trait of the plant, sinigrin concentration. * It was found that
      generalist damage was negatively correlated but specialist loads were positively
      correlated with increasing sinigrin concentrations; and sinigrin concentration
      was favored when specialists were removed, disfavored (past an intermediate
      point) when generalists were removed and selectively neutral when plants faced
      both generalists and specialists.

PMID- 17547678
TI  - Sexing pollen reveals female bias in a dioecious plant.
AB  - * Information on angiosperm sex ratios has largely been restricted to surveys of
      flowering individuals. These often deviate from equality, with male bias more
      commonly reported. Female-biased sex ratios are concentrated in a few taxa and
      have been linked to the possession of heteromorphic sex chromosomes and bias
      introduced during the gametophytic stage of the life cycle. It has been proposed
      that differences in gamete quantity and quality could give rise to female bias,
      although there is no direct evidence with which to evaluate this possibility. *
      Here, we use flow cytometry to investigate microgametophytic 'sex ratios' in a
      flowering plant. We demonstrate that differences in DNA content between the sexes
      in Rumex nivalis, a species with heteromorphic sex chromosomes, make it possible
      to distinguish female- vs male-determining pollen nuclei. * We found a small but
      significant female bias in microgametophytes produced by males (mean 0.515) with
      significant variation among family means (range 0.463-0.586), and 18 of 22
      families averaging > 0.50. * The observed female bias at the gametophytic stage
      of the life cycle is consistent with the direction of bias previously reported
      for seeds and vegetative and reproductive plants in wild populations of R.
      nivalis, but is insufficient to fully explain the degree of bias.

PMID- 17547679
TI  - Corticosteroid-binding globulin gene polymorphisms: clinical implications and
      links to idiopathic chronic fatigue disorders.
AB  - Corticosteroid-binding globulin (CBG) binds cortisol with high affinity,
      facilitating transport of cortisol in blood, although tissue-specific CBG
      cortisol interactions have long been postulated. There are three heritable, human
      CBG gene mutations that can reduce CBG-cortisol binding affinity and/or reduce
      circulating CBG levels. In some families, fatigue and low blood pressure have
      been associated with affinity altering or CBG level reducing mutations. The
      limited numbers of reports raise the possibility of ascertainment bias as many
      cases presented with features suggesting cortisol deficiency. The recent
      description of a genetically CBG-deficient mouse listed fatigue, manifest as
      reduced activity levels, as part of the phenotype, which also included immune
      aberrations. Severe CBG mutations may produce fatigue, but one study suggests
      that these are a rare cause of idiopathic fatigue. A mechanism for the effect of
      CBG mutations on fatigue is not readily apparent because free cortisol levels are
      normal, although we speculate that CBG may have an effect on cortisol-brain
      transport.

PMID- 17547680
TI  - Two compound heterozygous mutations (c.215delA/c.2422T-->C and c.387delC/c.1159G-
      >A) in the thyroid peroxidase gene responsible for congenital goitre and iodide
      organification defect.
AB  - BACKGROUND: Iodide organification defects are frequently but not always
      associated with mutations in the thyroid peroxidase (TPO) gene and characterized
      by a positive perchlorate discharge test. These mutations phenotypically produce
      a congenital goitrous hypothyroidism, with an autosomal recessive mode of
      inheritance. OBJECTIVES: In the present study we extended our initial molecular
      studies in six unrelated patients heterozygous for the TPO mutations, in order to
      identify the second mutation in this autosomal recessive disease. METHODS: The
      promoter and the complete coding regions of the human TPO and DUOXA2 genes, along
      with the flanking regions of each intron were analysed by direct DNA sequencing.
      RESULTS: Four different inactivating TPO mutations were identified in two
      patients: two novel mutations (c.215delA [p.Q72fsX86] and c.1159G-->A [p.G387R])
      and two previously reported (c.387delC [p.N129fsX208] and c.2422T-->C [p.C808R]),
      confirming the inheritance of two different compound heterozygous mutations,
      c.215delA/c.2422T-->C and c.387delC/c.1159G-->A. The remaining four patients did
      not show additional inactivating mutations in the TPO gene and all had only the
      wild type sequencing in the DUOXA2 gene. CONCLUSIONS: We have reported two
      patients with iodide organification defect caused by two compound heterozygous
      mutations, c.215delA/c.2422T-->C [p.Q72fsX86/p.C808R] and c.387delC/c.1159G-->A
      [p.N129fsX208/p.G387R], in the TPO gene and four patients with monoallelic TPO
      defect. Identification of the molecular basis of this disorder might be helpful
      for understanding the pathophysiology of congenital hypothyroidism.

PMID- 17547681
TI  - A novel compound heterozygous mutation of the aromatase gene in an adult man:
      reinforced evidence on the relationship between congenital oestrogen deficiency,
      adiposity and the metabolic syndrome.
AB  - BACKGROUND: Descriptions of new cases of human aromatase deficiency are useful
      for a better understanding of male oestrogen pathophysiology, as some aspects
      remain controversial. OBJECTIVE: To present a new case of an adult man affected
      by aromatase deficiency, along with a description of clinical phenotype, and
      hormonal and genetic analysis. DESIGN: Case report study. PATIENT: A 25-year-old
      man with continuing linear growth, eunuchoid body habitus and diffuse bone pain.
      MEASUREMENTS: Amplification and sequencing of all coding exons with their
      flanking intronic sequences of the CYP19A1 gene. Aromatase expression of the
      mutant human cDNAs was compared with wild type. Serum LH, FSH, testosterone,
      oestradiol, insulin, glucose, glycosylated haemoglobin (HbA1c), serum lipids and
      liver enzymes were measured. Histological analysis of liver and testis biopsies
      was performed. RESULTS: Two novel heterozygous compound inactivating mutations of
      the CYP19A1 gene were disclosed. The first mutation is at bp380 (T-->G) in exon
      IV and the second one at bp 1124 (G-->A) in exon IX. LH and testosterone were
      normal, FSH was slightly elevated, and serum oestradiol undetectable. The subject
      showed a metabolic syndrome characterized by abdominal obesity,
      hyperinsulinaemia, acanthosis nigricans and nonalcoholic fatty liver disease.
      CONCLUSIONS: These novel mutations improve our knowledge on genetics of the
      CYP19A1 gene. This new case of aromatase deficiency sheds new light on the
      heterogeneity of mutations in the CYP19A1 gene causing loss of function of the
      aromatase enzyme. The evidence of metabolic syndrome and of obesity associated
      with congenital oestrogen deprivation emphasizes the role of oestrogens in fat
      accumulation and distribution in men, a role that has long been partially
      overlooked in these patients.

PMID- 17547682
TI  - The Leu544Ile polymorphism of the growth hormone receptor gene affects the serum
      cholesterol levels during GH treatment in children with GH deficiency.
AB  - OBJECTIVE: The cellular effects of growth hormone (GH) are mediated by the
      interaction between GH and the GH receptor (GHR). We investigated the association
      between polymorphisms in GHR and changes in height standard deviation scores
      (SDS), and lipid metabolism during GH treatment for GH-deficient children.
      DESIGN: A 1-year study on growth rate and lipid metabolism under GH treatment.
      PATIENTS: Eighty-three children (61 boys and 22 girls) with GH deficiency were
      treated with GH for 1 year after diagnosis. INTERVENTION: The patients were
      treated with recombinant human GH (0.19 mg/kg/week) for at least 1 year after
      diagnosis. The growth rates and biochemical parameters for lipid metabolism were
      measured both before and during treatment. Four single nucleotide polymorphisms
      (SNPs) in the GHR gene, Cys440Phe, Pro495Thr, Leu544Ile and Pro579Thr, and exon 3
      deletion polymorphisms were genotyped by direct sequencing and multiplex PCR.
      RESULTS: We found no significant association between GHR polymorphisms and
      changes in height SDS during GH treatment. The total cholesterol levels of the GH
      deficient boys with Ile/Ile at codon 544 showed significantly higher cholesterol
      levels before GH treatment and then maintained high levels during the GH
      treatment, compared to those with other genotypes. No other polymorphisms seemed
      to have any apparent effects on lipid metabolism. CONCLUSION: The Leu544Ile
      polymorphism of the GHR gene is associated with cholesterol levels in boys with
      GH deficiency.

PMID- 17547683
TI  - Serum resistin in gestational diabetes mellitus and early postpartum.
AB  - OBJECTIVES: To observe the alterations in serum resistin in gestational diabetes
      (GDM) and the early postpartum period, and compare this to nondiabetic
      pregnancies in order to evaluate the role of serum resistin in gestational
      diabetes mellitus. DESIGN: A cross-sectional study. PATIENTS: Twenty women with
      normal pregnancy and 20 with gestational diabetes. MEASUREMENTS: Serum resistin
      concentration was assayed by ELISA. RESULTS: Serum resistin concentration was
      significantly higher in women with GDM than in controls before delivery. Serum
      levels of resistin significantly decreased after delivery in both the GDM group
      and controls (P < 0.001 for both). There was a trend of higher serum resistin in
      women with GDM than in controls. Differences existed on days 1 (P < 0.001) and 3
      (P = 0.013), but not by day 5 (P = 0.052) after delivery. CONCLUSIONS: Elevated
      serum resistin level was observed in women with gestational diabetes, suggesting
      that it is important in the pathology of the disease.

PMID- 17547684
TI  - Impact of the Y-containing cell line on histological differentiation patterns in
      dysgenetic gonads.
AB  - OBJECTIVE: Gonadal karyotyping is considered a tool for increasing our knowledge
      of disturbed gonadal development in patients with gonadal dysgenesis and for
      estimating more accurately the risk for gonadoblastoma formation. The objective
      was to gain insight into the role of Y chromosome distribution in the
      histological heterogeneity of gonads of patients with gonadal dysgenesis. DESIGN:
      Investigation of the possible relationship between peripheral blood karyotype,
      gonadal karyotype, morphological differentiation patterns of dysgenetic gonads
      and tumour formation. PATIENTS: In total 22 gonadal samples from 19 patients with
      gonadal dysgenesis (45,X/46,XY and variants n = 14; 46,XY: n = 3; 46,XX: n = 2)
      were examined. MEASUREMENTS: Morphological examination and immunohistochemical
      staining for testis specific protein, Y encoded (TSPY) and fluorescent and
      nonfluorescent in situ hybridization directly on gonadal tissue. RESULTS: No
      correlation was observed between peripheral blood karyotype and gonadal karyotype
      or between gonadal karyotype and the corresponding differentiation pattern. A Y
      containing cell line in Sertoli cells was encountered no more frequently than
      were other cell types. CONCLUSIONS: The distribution of the Y-containing cell
      line in peripheral blood is not a suitable indicator for predicting the
      histological differentiation pattern found in the gonads of patients with gonadal
      dysgenesis. The analysis of Y-containing cell lines in the gonads of such
      patients could be informative with regard to the specific characteristics of
      gonadal development in humans as compared to chimeric mouse models. Moreover, it
      is essential to understand the mechanisms underlying disturbed gonadogenesis in
      these patients. As the gonadal karyotype is not related to the encountered
      gonadal differentiation pattern, it does not allow prediction of the risk for
      gonadoblastoma formation.

PMID- 17547685
TI  - Impact of the high-molecular-weight form of adiponectin on endothelial function
      in healthy young men.
AB  - OBJECTIVE: Adiponectin is an adipocyte-derived, antiatherogenic protein that is
      present in plasma as a large multimeric structure of high molecular weight (HMW)
      and in a trimer or hexamer form (non-HMW). The biological activities of these
      isoforms have not yet been elucidated. We therefore examined the effect of these
      isoforms on endothelial function in healthy young men. DESIGN: One hundred
      apparently healthy young men without overt cardiovascular disease (mean age 30
      years) were recruited in this cross-sectional study based on voluntary
      enrollment. MEASUREMENTS: We evaluated endothelial function estimated by flow
      mediated dilatation (FMD) of the brachial artery during reactive hyperaemia, and
      measured total and HMW adiponectin levels. RESULTS: Both HMW and non-HMW
      adiponectin levels showed a significant, inverse correlation with body mass index
      (BMI). FMD was significantly correlated with fasting insulin, homeostasis model
      assessment of insulin resistance (HOMA-IR), malondialdehyde-modified low density
      lipoprotein (MDA-LDL), LDL particle size, and HMW adiponectin (r = 0.320, P =
      0.001), but not non-HMW adiponectin (r = 0.125, P = 0.22). In multivariate
      analysis, HMW adiponectin and MDA-LDL were selected as independent factors
      capable of influencing FMD. No variables determined nitroglycerin-induced
      dilatation. CONCLUSIONS: These results suggest that even in young men, plasma
      adiponectin levels can predict endothelial dysfunction before any overt vascular
      disease has occurred. HMW adiponectin may be more useful as a marker of
      endothelial dysfunction than total adiponectin.

PMID- 17547686
TI  - Bone mineral density remains stable in HAART-treated HIV-infected men over 2
      years.
AB  - OBJECTIVE: Recently we reported that human immunodeficiency virus (HIV)-infected
      Caucasian men treated with highly active antiretroviral therapy (HAART) have
      normal weight-adjusted bone mineral density (BMD), in contrast to most other
      cross-sectional analyses, which have reported low BMD in HIV-infected patients.
      We have now addressed the question of whether there is accelerated BMD loss over
      time in HIV-infected men. DESIGN: A 2-year, prospective, longitudinal study.
      SUBJECTS: Twenty-three HAART-treated, HIV-infected men and 26 healthy controls.
      MEASUREMENTS: All participants had measurements of BMD and bone-related
      laboratory parameters at baseline, and a repeat measurement of BMD at 2 years.
      RESULTS: In the HIV-infected men the mean age was 47 years, the mean duration of
      infection was 8.2 years, and the mean duration of HAART was 54 months. Over 2
      years of follow-up, BMD increased from baseline in the HIV-infected men by 2.6%
      at the lumbar spine (P = 0.05 vs. baseline), and remained stable at the total hip
      (mean change 0.1%, P > 0.99) and total body (mean change 0.6%, P = 0.39). Mean
      changes in BMD in the control group were 1.4% at the lumbar spine, -0.1% at the
      total hip, and -0.8% at the total body. The HIV-infected men lost less total body
      BMD than the control group (P = 0.01). In the HIV-infected men, body weight
      remained stable over 2 years while fat mass decreased and lean mass tended to
      increase, whereas in the controls, body weight and fat mass increased while lean
      mass remained stable. CONCLUSIONS: Accelerated bone loss does not occur in HIV
      infected men treated with HAART. Monitoring of BMD in HIV-infected men may not be
      necessary.

PMID- 17547687
TI  - Free triiodothyronine and thyroid stimulating hormone are directly associated
      with waist circumference, independently of insulin resistance, metabolic
      parameters and blood pressure in overweight and obese women.
AB  - OBJECTIVE: To examine whether obesity, body fat distribution and insulin
      resistance have an independent effect on serum TSH and free thyroid hormones (FT3
      and FT4) in a cohort of euthyroid women, represented by overweight and obese
      patients. DESIGN AND PATIENTS: A total of 201 women, aged 18-68 years, with body
      mass index (BMI) > or = 25.0 kg/m(2) and TSH levels < 4.0 mU/l were investigated.
      MEASUREMENTS: Fasting TSH, FT3, FT4, insulin, glucose, and serum lipid
      concentrations, and the level of insulin resistance, estimated by the homeostasis
      model assessment for insulin resistance (HOMA-IR). Waist circumference was
      measured as an indirect parameter of central fat accumulation. RESULTS: FT3 was
      directly associated with BMI (P < 0.01) and waist circumference (P < 0.01), and
      negatively correlated with age (P < 0.001). FT4 was negatively associated with
      HOMA-IR (P < 0.05) and fasting insulin levels (P < 0.05). TSH was positively
      correlated with waist circumference (P < 0.05) and negatively associated with age
      (P < 0.05). When multiple regression analysis was performed with FT3 as the
      dependent variable, and waist circumference, HOMA-IR, blood pressure levels and
      serum lipid concentrations as independent variables, FT3 maintained an
      independent association only with waist circumference (positive, P < 0.05) and
      age (negative, P < 0.001). When multiple regression analysis was performed with
      TSH as the dependent variable, and the above parameters as independent variables,
      TSH maintained an independent association only with waist circumference
      (positive, P < 0.05) and age (negative, P < 0.05). By contrast, when multiple
      regression analysis was performed with FT4 as the dependent variable, FT4 did not
      maintain an independent association with any of the independent parameters.
      CONCLUSIONS: Progressive central fat accumulation is associated with an increase
      in both FT3 and TSH serum levels, independently of insulin sensitivity, metabolic
      parameters and blood pressure. These results suggest that (1) progressive central
      fat accumulation is associated with a parallel increase in FT3 levels, possibly
      as an adaptive thermogenic phenomenon, and (2) the control of TSH secretion by
      free thyroid hormones is possibly impaired in obesity.

PMID- 17547688
TI  - Age-, gender-, and weight-related effects on levels of 25-hydroxyvitamin D are
      not mediated by vitamin D binding protein.
AB  - OBJECTIVE: 25-hydroxyvitamin D (25OHD) levels are inversely related to body
      weight, and have been reported to decline with age and be lower in women than
      men. We hypothesized that these findings might be explained by effects of these
      variables on vitamin D binding protein (DBP) levels. We set out to determine the
      relationships between DBP and gender, 25OHD, body weight and body composition.
      DESIGN: Cross-sectional analysis. PATIENTS: One hundred healthy, middle-aged and
      older, community-dwelling men and women. MEASUREMENTS: All participants were
      measured for 25OHD, DBP, body weight, bone mineral density and body composition.
      RESULTS: Women had higher mean DBP levels than men but lower total 25OHD levels
      [DBP: women, mean (SD) 339 (36) mg/l, men 307 (71) mg/l, P = 0.005; 25OHD: women
      67 (23) nmol/l, men 91 (39) nmol/l, P < 0.001]. In women, there were significant
      positive relationships between DBP and albumin (r = 0.33) and 25OHD (r = 0.34)
      whereas in men there were no significant relationships between DBP and any
      measured variables. There was no significant relationship between DBP and age,
      body weight, body mass index, fat mass or percentage fat in men or women.
      CONCLUSION: We found no evidence to support the hypothesis that DBP levels are
      related to age, or adiposity. The changes in 25OHD levels with age, gender, or
      fat mass are not due to underlying relationships between DBP and these variables.
      This suggests that the relationships consistently observed between 25OHD and body
      composition and gender are of biological origin and not due to adaptation to
      changes in transport proteins.

PMID- 17547689
TI  - Elevated levels of growth-related hormones in autism and autism spectrum
      disorder.
AB  - OBJECTIVE: Children with autism are known to have larger head circumferences;
      whether they are above average in height and weight is less clear. Moreover,
      little is known about growth-related hormone levels in children with autism. We
      investigated whether children with autism were taller and heavier, and whether
      they had higher levels of growth-related hormones than control children did.
      DESIGN: A case-control study design was employed. PATIENTS: Boys with autism
      spectrum disorder (ASD) or autism (n = 71) and age-matched control boys (n = 59)
      were evaluated at Cincinnati Children's Hospital. MEASUREMENTS: Height, weight
      and head circumference were measured. Blood samples were assayed for IGF-1 and 2,
      IGFBP-3, growth hormone binding protein (GHBP) and for dehydroepiandrosterone
      (DHEA) and DHEA sulphate (DHEAS). RESULTS: Subjects with autism/ASD had
      significantly (P = 0.03) greater head circumferences (mean z-score 1.24, SD 1.35)
      than controls (mean z-score 0.78, SD 0.93). Subjects with autism also had
      significantly (P = 0.01) greater weights (mean z-score 0.91, SD 1.13) than
      controls (mean z-score 0.41, SD 1.11). Height did not differ significantly
      between groups (P = 0.65); subjects with autism/ASD had significantly (P = 0.003)
      higher body mass indices (BMI) (mean z-score 0.85, SD 1.19) than controls (mean z
      score 0.24, SD 1.17). Levels of IGF-1, IGF-2, IGFBP-3 and GHBP in the group with
      autism/ASD were all significantly higher (all P < or = 0.0001) than in controls.
      CONCLUSIONS: Children with autism/ASD had significantly higher levels of many
      growth-related hormones: IGF-1, IGF-2, IGFBP-3 and GHBP. These findings could
      help explain the significantly larger head circumferences and higher weights and
      BMIs seen in these subjects. Future studies should examine the potential role of
      growth-related hormones in the pathophysiology of autism.

PMID- 17547690
TI  - Screening of Cushing's syndrome in adult patients with newly diagnosed diabetes
      mellitus.
AB  - OBJECTIVE: Recent studies have shown that a relatively high number of diabetic
      patients may have unsuspected Cushing's syndrome (CS). The aim of the present
      study was to screen for CS in adult patients with newly diagnosed diabetes
      mellitus who were not selected for clinical characteristics, such as poor control
      and obesity, which may increase the pre-test probability of CS. DESIGN, PATIENTS
      AND MEASUREMENT: We prospectively evaluated 100 consecutive diabetic patients at
      diagnosis from 2003 to 2004. No patient had clear Cushingoid features. Screening
      was performed by using the overnight 1-mg dexamethasone suppression test (DST)
      after complete recovery from acute concomitant illnesses and attainment of
      satisfactory glycaemic control. The threshold of adequate suppression after DST
      was set at 110 nmol/l. RESULTS: Five patients failed to suppress cortisol after
      DST and underwent a repeated DST and a confirmatory standard 2-day, 2-mg DST
      after 3-6 months from the baseline evaluation. In one woman, a definitive
      diagnosis of CS was made by a surgically proven pituitary adenoma, and glycaemic
      control improved after cure of CS. CONCLUSIONS: The results of the present study
      support the view that unknown CS is not rare among patients with diabetes
      mellitus. This is the first demonstration that screening for CS may be feasible
      at the clinical onset of diabetes in an unselected cohort of patients. Therefore,
      early diagnosis and treatment of CS may provide the opportunity to improve the
      prognosis of diabetes.

PMID- 17547691
TI  - Hyperthyroidism may affect serum N-terminal pro-B-type natriuretic peptide levels
      independently of cardiac dysfunction.
AB  - BACKGROUND AND AIM: It is known that NT-proBNP levels increase in cardiac
      failure. However, NT-proBNP levels in different thyroid states are still unclear.
      We aimed to evaluate serum NT-proBNP levels in both hyperthyroid and hypothyroid
      patients without cardiac insufficiency. SUBJECTS AND METHODS: Thirty-six patients
      with hyperthyroidism (42.9 +/- 16.7 years), 25 patients with hypothyroidism (35.4
      +/- 13.9 years) and 34 age-matched euthyroid subjects (41.4 +/- 13.8 years) were
      included in the study. After anthropometric evaluations, body fat analyses were
      determined by bioelectrical impedance. Electrocardiography and echocardiography
      were used in cardiac evaluations. Serum NT-proBNP was measured by immunoassay.
      RESULTS: Mean serum NT-proBNP levels in hyperthyroid patients were higher than in
      both control subjects (13.65 +/- 13.02 vs. 6.50 +/- 4.83 pmol/l, P = 0.002) and
      hypothyroid patients (13.65 +/- 13.02 vs. 5.98 +/- 5.08 pmol/l, P = 0.003).
      However, mean serum NT-proBNP levels in hypothyroid patients were not different
      from those in control subjects. There was a positive correlation between serum NT
      proBNP and thyroid hormones (NT-proBNP and FT3: r = 0.324, P = 0.001; NT-proBNP
      and FT4: r = 0.269, P = 0.009, respectively). Serum NT-proBNP levels were
      positively correlated with left ventricle end-diastolic diameters (r = 0.232, P =
      0.04), interventricular septum thickness (r = 0.315, P = 0.006), and negatively
      correlated with left ventricular ejection fraction (r = -0.238, P = 0.04).
      CONCLUSIONS: Serum NT-proBNP levels may increase in hyperthyroidism independently
      of cardiac insufficiency. Therefore, hyperthyroidism may lead to cardiac
      ultrastructural changes undetermined by conventional echocardiography and these
      changes may be responsible for elevation of NT-proBNP levels. In contrast to
      decreased thyroid hormones, excess thyroid hormones may have a more pronounced
      effect on serum NT-proBNP levels.

PMID- 17547692
TI  - Genetic polymorphism of CYP2D6 influences susceptibility to papillary thyroid
      cancer.
AB  - OBJECTIVE: Xenobiotic-metabolizing enzymes are widely polymorphic and confer
      interindividual variation in the ability to detoxify carcinogens or to activate
      pro-carcinogens. A common polymorphism of cytochrome P450 2D6 (CYP2D6) results in
      lack of enzyme activity and has been associated with an altered susceptibility to
      several cancers. The aim of this study was to investigate the association between
      the CYP2D6 poor metaboliser genotype and the risk of papillary thyroid cancer
      (PTC). DESIGN: Retrospective case-control study. PATIENTS: One hundred and eighty
      seven patients with PTC and 256 controls. MEASUREMENTS: Genotyping was performed
      by PCR and restriction enzyme analysis to detect the presence of the common
      CYP2D6*4 poor metaboliser allele. RESULTS: The frequency of individuals with the
      homozygous poor metaboliser genotype was lower in the patient group [1.6 vs.
      5.5%, P = 0.037, OR = 0.28 (95% CI 0.09-0.93)]. The CYP2D6*4 allele frequency was
      also lower in the patient group [13.4 vs. 21.7%, P = 0.002, OR = 0.56 (95% CI
      0.39-0.80)]. CONCLUSIONS: The results suggest that the poor metaboliser genotype
      is associated with a protective effect against PTC. This could be explained by a
      possible role of CYP2D6 on the metabolic activation of putative environmental
      chemical thyroid carcinogens or by linkage to another cancer-causing gene.
      Further research may allow the identification of metabolic risk factors and
      contribute towards understanding the molecular mechanisms involved in thyroid
      carcinogenesis.

PMID- 17547693
TI  - Seasonal variation in serum concentrations of reproductive hormones and urinary
      excretion of 6-sulfatoxymelatonin in men living north and south of the Arctic
      Circle: a longitudinal study.
AB  - OBJECTIVE: Seasonal variation in photoperiod or temperature may influence human
      reproductive biology. The present study evaluated whether seasonal changes
      occurred in the levels of reproductive hormones and the major melatonin
      metabolite, 6-sulfatoxymelatonin (aMT6s), in populations exposed to extreme
      variation in photoperiod and temperature. DESIGN: Two separate cohorts of
      Norwegian men were recruited from the general population in either of two
      locations: Tromso (69.5 degrees N, n = 92) or Oslo (60 degrees N, n = 112),
      located north and south of the Arctic Circle (66.5 degrees N), respectively.
      MEASUREMENTS: Four blood and 12-h overnight urine samples were obtained on
      separate occasions over a 12-month period, including during the photoperiod
      maximum and minimum. Serum concentrations of FSH, LH, testosterone (T),
      oestradiol (E(2)), SHBG and the urinary excretion of aMT6s were assessed.
      RESULTS: Statistical analysis using generalized estimating equations indicated
      that LH levels were lowest during early winter in both locations (both P = 0.01).
      In Tromso, free T and E(2) concentrations peaked during early winter (P = 0.02
      and 0.003, respectively). In Oslo, free T levels were lowest during early winter
      (P = 0.06) whereas E(2) levels were lowest during late summer (P < 0.001).
      Urinary aMT6s concentrations were lowest during early summer in Tromso and Oslo.
      Concentrations peaked during early winter in Tromso (P < 0.001) and during late
      winter in Oslo (P < 0.001). CONCLUSIONS: LH levels exhibited similar changes in
      both locations, whereas the patterns of changes of the sex steroid concentrations
      differed, possibly indicating different underlying mechanisms. Excretion of aMT6s
      was lowest during early summer in both locations, indicating that the long
      natural photoperiod was sufficient to cause suppression of melatonin secretion.
      Whether these changes have any biological significance remains uncertain.

PMID- 17547694
TI  - Activation of Stat5 and induction of a pregnancy-like mammary gland
      differentiation by eicosapentaenoic and docosapentaenoic omega-3 fatty acids.
AB  - The protective effect of early pregnancy against breast cancer can be attributed
      to the transition from undifferentiated cells in the nulliparous to the
      differentiated mature cells during pregnancy. Considerable evidence suggests
      strongly that the n-3 polyunsaturated fatty acid (PUFA) content of adipose breast
      tissue is inversely associated with an increased risk of breast cancer. Here, we
      report that there was a decrease in the n-6/n-3 PUFA ratio and a significant
      increase in concentration of n-3 PUFA docosapentaenoic acid and eicosapentaenoic
      acid in the pregnant gland. The functional role of n-3 PUFAs on differentiation
      was supported by the studies in the fat-1 transgenic mouse, which converts
      endogenous n-6 to n-3 PUFAs. Alternation of the n-6/n-3 ratio in favor of n-3
      PUFA, and particularly docosapentaenoic acid, in the mammary gland of fat-1 mouse
      resulted in development of lobulo-alveolar-like structure and milk protein beta
      casein expression, mimicking the differentiated state of the pregnant gland.
      Docosapentaenoic acid and eicosapentaenoic acid activated the Jak2/Stat5
      signaling pathway and induced a functional differentiation with production of
      beta-casein. Expression of brain type fatty acid binding protein brain type fatty
      acid binding protein in virgin transgenic mice also resulted in a reduced ratio
      of n-6/n-3 PUFA, a robust increase in docosapentaenoic acid accumulation, and
      mammary differentiation. These data indicate a role of mammary derived growth
      inhibitor related gene for preferential accumulation of n-3 docosapentaenoic acid
      and eicosapentaenoic acid in the differentiated gland during pregnancy. Thus,
      alternation of n-6/n-3 fatty acid compositional ratio in favor of n-3 PUFA, and
      particularly docosapentaenoic acid and eicosapentaenoic acid, is one of the
      underlying mechanisms of pregnancy-induced mammary differentiation.

PMID- 17547696
TI  - The conserved isoleucine-valine-phenylalanine motif couples activation state and
      endocytic functions of beta-arrestins.
AB  - Beta-arrestins (betaarrs) play a central role in the regulation of G-protein
      coupled receptors (GPCRs). Their binding to phosphorylated activated GPCRs
      induces a conformational transition to an active state resulting in the release
      of their flexible C-terminal tail. Binding sites for clathrin and the adaptor
      protein (AP)-2 clathrin adaptor complex are then unmasked, which drive the
      recruitment of betaarrs-GPCR complexes into clathrin-coated pits (CCPs). A
      conserved isoleucine-valine-phenylalanine (IVF) motif of the C-terminal tail
      controls betaarr activation through intramolecular interactions. Here, we provide
      structural, biochemical and functional evidence in living cells that the IVF
      motif also controls binding to AP-2. While the F residue is directly involved in
      AP-2 binding, substitutions of I and V residues, markedly enhanced affinity for
      AP-2 resulting in active betaarr mutants, which are constitutively targeted to
      CCPs in the absence of any GPCR activation. Conformational change and endocytic
      functions of betaarrs thus appear to be coordinated via the complex molecular
      interactions established by the IVF motif.

PMID- 17547695
TI  - An acidic cluster of the cytoplasmic tail of the RD114 virus glycoprotein
      controls assembly of retroviral envelopes.
AB  - Retroviral core proteins, Gag and envelope (Env) glycoproteins are expressed from
      distinct cellular areas and therefore need to encounter to assemble infectious
      particles. The intrinsic cell localisation properties of either viral component
      or their capacity to mutually interact determines the assembly of infectious
      particles. Here, we address how Env determinants and cellular sorting proteins
      allow the Env derived from gamma retroviruses, murine leukemia virus (MLV) and
      RD114, to travel to or from late endosomes (LE), which may represent the Env
      assembly site of retroviruses in some cells. The individual expression of MLV Env
      resulted in its accumulation in LE in contrast to RD114 Env that required the
      presence of gamma retroviral Gag proteins. To discriminate between intrinsic
      intracellular Env localisation and gamma retroviral Gag/Env interactions in
      influencing Env viral incorporation, we studied Env assembly on heterologous
      lentiviral particles on which they are passively recruited. We found that an
      acidic cluster present at the C-terminus of the RD114 Env cytoplasmic tail
      determines its sub-cellular localisation and retrograde transport. Mutation of
      this motif induced late endosomal concentration of the RD114 Env, correlating
      with increased viral incorporation and infectivity. Reciprocally, the
      reinforcement of a poorly functional acidic motif in the MLV Env resulted in a
      marked decrease of its late endosomal localisation, leading to weakly infectious
      lentiviral particles with low Env densities. Finally, through upregulation versus
      downregulation of its cellular expression, we show that phosphofurin acidic
      cluster-sorting protein 1 (PACS-1) controls the function of the RD114 Env acidic
      cluster, assigning to this cellular effector a crucial role in modulation of Env
      assembly of some retroviruses.

PMID- 17547697
TI  - RhoB-dependent modulation of postendocytic traffic in polarized Madin-Darby
      canine kidney cells.
AB  - The Rho family of GTPases is implicated in the control of endocytic and
      biosynthetic traffic of many cell types; however, the cellular distribution of
      RhoB remains controversial and its function is not well understood. Using
      confocal microscopy, we found that endogenous RhoB and green fluorescent protein
      tagged wild-type RhoB were localized to early endosomes, and to a much lesser
      extent to recycling endosomes, late endosomes or Golgi complex of fixed or live
      polarized Madin-Darby canine kidney cells. Consistent with RhoB localization to
      early endosomes, we observed that expression of dominant-negative RhoBN19 or
      dominant-active RhoBV14 altered postendocytic traffic of ligand-receptor
      complexes that undergo recycling, degradation or transcytosis. In vitro assays
      established that RhoB modulated the basolateral-to-apical transcytotic pathway by
      regulating cargo exit from basolateral early endosomes. Our results indicate that
      RhoB is localized, in part, to early endosomes where it regulates receptor egress
      through the early endocytic system.

PMID- 17547698
TI  - Clathrin-mediated endocytosis at synapses.
AB  - Neurons are communication specialists that convert electrical into chemical
      signals at specialized cell-cell junctions termed synapses. Arrival of an action
      potential triggers calcium-regulated exocytosis of neurotransmitter (NT) from
      small synaptic vesicles (SVs), which then diffuses across the synaptic cleft and
      binds to postsynaptic receptors to elicit specific changes within the
      postsynaptic cell. Endocytosis of pre- and postsynaptic membrane proteins
      including SV components and postsynaptic NT receptors is essential for the proper
      functioning of the synapse. During the past several years, we have witnessed
      enormous progress in our understanding of the mechanics of clathrin-mediated
      endocytosis (CME) and its role in regulating exo-endocytic vesicle cycling at
      synapses. Here we summarize the molecular machinery used for recognition of
      synaptic membrane protein cargo and its clathrin-dependent internalization, and
      describe the inventory of tools that can be used to monitor vesicle cycling at
      synapses or to inhibit CME in a stage-specific manner.

PMID- 17547699
TI  - A di-acidic sequence motif enhances the surface expression of the potassium
      channel TASK-3.
AB  - We have characterized a sequence motif, EDE, in the proximal C-terminus of the
      acid-sensitive potassium channel TASK-3. Human TASK-3 channels were expressed in
      Xenopus oocytes, and the density of the channels at the surface membrane was
      studied with two complementary techniques: a luminometric surface expression
      assay of hemagglutinin epitope-tagged TASK-3 channels and voltage-clamp
      measurements of the acid-sensitive potassium current. Both approaches showed that
      mutation of the two glutamate residues of the EDE motif to alanine (ADA mutant)
      markedly reduced the transport of TASK-3 channels to the cell surface. Mutation
      of the central aspartate of the EDE motif had no effect on surface expression.
      The functional role of the EDE motif was further characterized in chimaeric
      constructs consisting of truncated Kir2.1 channels to which the C-terminus of
      TASK-3 was attached. In these constructs, too, replacement of the EDE motif by
      ADA strongly reduced surface expression. Live-cell imaging of enhanced green
      fluorescent protein-tagged channels expressed in COS-7 cells showed that 24 h
      after transfection wild-type TASK-3 was mainly localized to the cell surface
      whereas the ADA mutant was largely retained in the endoplasmic reticulum (ER).
      Mutation of a second di-acidic motif in the C-terminus of TASK-3 (DAE) had no
      effect on surface expression. Coexpression of TASK-3 with a GTP-restricted mutant
      of the coat recruitment GTPase Sar1 (Sar1H79G) resulted in ER retention of the
      channel. Our data suggest that the di-acidic motif, EDE, in human TASK-3 is a
      major determinant of the rate of ER export and is required for efficient surface
      expression of the channel.

PMID- 17547700
TI  - Notch signaling--constantly on the move.
AB  - The Notch pathway is a highly conserved and ubiquitous signaling system that
      functions in determining a diverse array of cell fates and regulates many
      cellular processes during embryonic development and throughout adulthood. Links
      to cancer, stroke and Alzheimer's disease underscore the need to define the
      molecular basis of Notch activation. Notch signaling is induced through direct
      cell-cell interactions that promote receptor activation following engagement with
      a membrane-bound Delta, Serrate, Lag-2 (DSL) ligand on adjacent cells. Cells take
      on distinct fates because Notch signaling is consistently activated in only one
      of the two interacting cells, highlighting the importance of establishing and
      maintaining signaling polarity. Studies in flies and worms have identified
      positive and negative transcriptional feedback mechanisms that amplify small
      differences in Notch and DSL ligand expression to bias which cells send or
      receive signals. However, endocytosis by signal-sending and signal-receiving
      cells also appears critical for directing and regulating Notch activation. In
      particular, endocytosis and membrane trafficking of DSL ligands, Notch and
      modulators can determine the competence of cells to send or receive signals that
      ensure reproducibility in generating cell types regulated by Notch signaling.

PMID- 17547701
TI  - Endocytosis at ribbon synapses.
AB  - Unlike conventional synaptic terminals that release neurotransmitter episodically
      in response to action potentials, neurons of the visual, auditory and vestibular
      systems encode sensory information in graded signals that are transmitted at
      their synapses by modulating the rate of continuous release. The synaptic ribbon,
      a specialized structure found at the active zones of these neurons, is necessary
      to sustain the high rates of exocytosis required for continuous release. To
      maintain the fidelity of synaptic transmission, exocytosis must be balanced by
      high-capacity endocytosis, to retrieve excess membrane inserted during vesicle
      fusion. Capacitance measurements following vesicle release in ribbon-type neurons
      indicate two kinetically distinct phases of compensatory endocytosis, whose
      relative contributions vary with stimulus intensity. The two phases can be
      independently regulated and may reflect different underlying mechanisms operating
      on separate pools of recycling vesicles. Electron microscopy shows diversity
      among ribbon-type synapses in the relative importance of clathrin-mediated
      endocytosis versus bulk membrane retrieval as mechanisms of compensatory
      endocytosis. Ribbon synapses, like conventional synapses, make use of multiple
      endocytosis pathways to replenish synaptic vesicle pools, depending on the
      physiological needs of the particular cell type.

PMID- 17547702
TI  - Annexins and endocytosis.
AB  - Annexins are calcium- and phospholipid-binding proteins that have been proposed
      to have multiple roles in membrane traffic. Historically, this has been based on
      the in vitro properties of annexins and their localization to specific membrane
      compartments. However, recent functional evidence supports a role for annexins in
      specific membrane traffic steps, although the requirement for annexins may be
      highly dependent on the cellular context. Here we review the roles of annexins in
      traffic within the endocytic pathway, focusing on clathrin-dependent
      internalization from the plasma membrane, multivesicular endosome/body (MVB)
      biogenesis and MVB-lysosome fusion.

PMID- 17547703
TI  - A family of aspartic proteases and a novel, dynamic and cell-cycle-dependent
      protease localization in the secretory pathway of Toxoplasma gondii.
AB  - Aspartic proteases are important virulence factors in pathogens like HIV, Candida
      albicans or Plasmodium falciparum. We report here the identification of seven
      putative aspartic proteases, TgASP1 to TgASP7, in the apicomplexan parasite
      Toxoplasma gondii. Bioinformatic and phylogenetic analysis of the TgASPs and
      other aspartic proteases from related Apicomplexa suggests the existence of five
      distinct groups of aspartic proteases with different evolutionary lineages. The
      members of each group share predicted biological features that validate the
      phylogeny. TgASP1 is expressed in tachyzoites, the rapidly dividing asexual stage
      of T.gondii. We present the proteolytic maturation and subcellular localization
      of this protease through the cell cycle. TgASP1 shows a novel punctate
      localization associated with the secretory system in non-dividing cells, and
      relocalizes dramatically and unambiguously to the nascent inner membrane complex
      of daughter cells at replication, before coalescing again at the end of division.

PMID- 17547704
TI  - Clathrin-coated pits: vive la difference?
AB  - Because of the discovery of coated pits and vesicles more than 40 years ago and
      the identification of clathrin as a major component of the coat, it has been
      assumed that clathrin-coated pits (CCPs) are responsible for the uptake of most
      plasma membrane receptors undergoing internalization. The recent molecular
      characterization of clathrin-independent routes of endocytosis confirms that
      several alternative endocytic pathways operate at the plasma membrane of
      mammalian cells. This heterogeneous view of endocytosis has been expanded still
      further by recent studies, suggesting that different subpopulations of CCPs
      responsible for the internalization of specific sets of cargo may coexist. In the
      present review, we have discussed the experimental evidence in favor or against
      the existence of distinct parallel clathrin-dependent pathways at the plasma
      membrane.

PMID- 17547705
TI  - Structure/function analysis of four core ESCRT-III proteins reveals common
      regulatory role for extreme C-terminal domain.
AB  - Endosomal sorting complex required for transport-III (ESCRT-III) is a large
      complex built from related ESCRT-III proteins involved in multivesicular body
      biogenesis. Little is known about the structure and function of this complex.
      Here, we compare four human ESCRT-III proteins - hVps2-1/CHMP2a, hVps24/CHMP3,
      hVps20/CHMP6, and hSnf7-1/CHMP4a - to each other, studying the effects of
      deleting predicted alpha-helical domains on their behavior in transfected cells.
      Surprisingly, removing approximately 40 amino acids from the C-terminus of each
      protein unmasks a common ability to associate with endosomal membranes and
      assemble into large polymeric complexes. Expressing these truncated ESCRT-III
      proteins in cultured cells causes ubiquitinated cargo to accumulate on enlarged
      endosomes and inhibits viral budding, while expressing full-length proteins does
      not. hVps2-1/CHMP2a lacking its C-terminal 42 amino acids further fails to bind
      to the AAA+ adenosine triphosphatase VPS4B/SKD1, indicating that C-terminal
      sequences are important for interaction of ESCRT-III proteins with VPS4. Overall,
      our study supports a model in which ESCRT-III proteins cycle between a default
      'closed' state and an activated 'open' state under control of sequences at their
      C-terminus and associated factors.

PMID- 17547706
TI  - Differential requirements for ts-O45-G and procollagen biosynthetic transport.
AB  - Emerging experimental evidence favours the existence of cargo sorting occurring
      upon the endoplasmic reticulum (ER) exit. Recent studies revealed that, in
      contrast to the conventional secretory marker ts-O45-G, procollagen (PC I) exits
      the ER at sites not coated with coat protein II and is transported to the Golgi
      complex in carriers devoid of coat protein I. Here, we investigated whether PC I
      trafficking requires a different molecular machinery in comparison with the ts
      O45-G. By combining colocalization of the cargoes with endogenous markers,
      downregulation of transport machinery by RNA interference and knock-ins by
      complementary DNA over-expression, we provide strong evidence that PC I and ts
      O45-G have common but also different molecular requirements during pre- and post
      Golgi trafficking events.

PMID- 17547707
TI  - Dysferlin in membrane trafficking and patch repair.
AB  - The muscular dystrophies are a heterogeneous group of inherited disorders,
      defined by progressive muscle weakness and atrophy. Following the discovery of
      dystrophin, remarkable progress has been made in defining the molecular
      properties of proteins involved in the various dystrophies. This has underlined
      the importance of the dystrophin-associated protein complex as a cell membrane
      scaffold, providing structural stability to muscle cells (McNeil PL, Khakee R.
      Disruptions of muscle fiber plasma membranes. Role in exercise-induced damage. Am
      J Pathol 1992;140:1097-1109). While the dystrophies linked to loss of function of
      dystrophin and its associated proteins are caused by diminished membrane
      integrity, it is now believed that a new class of dystrophies arises because of a
      diminished capacity for rapid muscle membrane repair after injury. Dysferlin is
      the first identified member of a putative muscle-specific repair complex that
      permits rapid resealing of membranes disrupted by mechanical stress. Membrane
      resealing is a function conserved by most cells and is mediated by a mechanism
      closely resembling regulated, Ca2+-dependent exocytosis. A primary role for
      dysferlin in this pathway, as a Ca2+-regulated fusogen, has been suggested, and a
      number of candidate partner proteins have been identified. This review outlines
      the current understanding of the role of dysferlin in membrane repair and the
      evolving picture of dysferlin-related signaling pathways in muscle cell
      physiology and pathology.

PMID- 17547708
TI  - Role of the innate immune system in host defence against bacterial infections:
      focus on the Toll-like receptors.
AB  - The innate immunity plays a critical role in host protection against pathogens
      and it relies amongst others on pattern recognition receptors such as the Toll
      like receptors (TLRs) and the nucleotide-binding oligomerization domains proteins
      (NOD-like receptors, NLRs) to alert the immune system of the presence of invading
      bacteria. Since their recent discovery less than a decade ago, both TLRs and NLRs
      have been shown to be crucial in host protection against microbial infections but
      also in homeostasis of the colonizing microflora. They recognize specific
      microbial ligands and with the use of distinct adaptor molecules, they activate
      different signalling pathways that in turns trigger subsequent inflammatory and
      immune responses that allows a immediate response towards bacterial infections
      and the initiation of the long-lasting adaptive immunity. In this review, we will
      focus on the role of the TLRs against bacterial infections in humans in contrast
      to mice that have been used extensively in experimental models of infections and
      discuss their role in controlling normal flora or nonpathogenic bacteria. We also
      highlight how bacteria can evade recognition by TLRs.

PMID- 17547709
TI  - Gallstone disease.
AB  - Gallstone disease is one of the most prevalent gastrointestinal diseases with a
      substantial burden to health care systems that is supposed to increase in ageing
      populations at risk. Aetiology and pathogenesis of cholesterol gallstones still
      are not well defined, and strategies for prevention and efficient nonsurgical
      therapies are missing. This review summarizes current concepts on the
      pathogenesis of cholesterol gallstones with focus on the uptake and secretion of
      biliary lipids and special emphasis on recent studies into the genetic
      background.

PMID- 17547710
TI  - The membrane protein universe: what's out there and why bother?
AB  - Chances are that you have come across membrane proteins many times in your
      professional life: ion channels, aquaporins, G-protein-coupled receptors, drug
      resistance proteins. But it is also quite likely that you have never bothered to
      think about what the implications are of being a membrane protein, as opposed to
      a soluble protein. What is special about membrane proteins in terms of structure
      and function, how many membrane proteins are out there, how are they made in the
      cell? Welcome to the membrane protein universe!

PMID- 17547711
TI  - Vitamin D status and parathyroid hormone levels in relation to blood pressure: a
      population-based study in older men and women.
AB  - BACKGROUND: Evidence is accumulating that the vitamin D endocrine system has
      physiological functions beyond bone health including a role in the regulation of
      blood pressure. Effects of poor vitamin D status on blood pressure may be
      mediated by elevated parathyroid hormone (PTH) levels. AIM: To evaluate whether
      serum 25-hydroxyvitamin D [25(OH)D] and PTH levels are independently associated
      with blood pressure in a population-based study of older men and women. METHODS:
      Subjects were participants of the Longitudinal Aging Study Amsterdam, aged 65
      years and older. In 1205 participants, serum 25(OH)D and PTH levels were
      determined and diastolic and systolic blood pressure were measured. Linear and
      logistic regression analyses were performed with adjustments for age, sex,
      region, season, lifestyle factors (physical activity, smoking, alcohol intake),
      and waist circumference. RESULTS: Serum 25(OH)D was not significantly associated
      with diastolic (beta 0.00, P = 0.98) or systolic (beta 0.06, P = 0.11) blood
      pressure. In contrast, higher ln-PTH levels were significantly associated with
      higher diastolic (beta 1.93, P = 0.03) and systolic (beta 4.67, P = 0.01) blood
      pressure. Higher PTH levels were associated with a substantially higher
      prevalence of hypertension (OR 2.00, 95% CI 1.31-3.06 for the highest versus the
      lowest quartile), whereas 25(OH)D showed no significant association (OR 0.89, 95%
      CI 0.47-1.69 for the lowest versus the highest 25(OH)D category). CONCLUSION:
      These results indicate that PTH is a potentially modifiable determinant of blood
      pressure in the general elderly population. Serum 25(OH)D, however, was not
      associated with blood pressure, possibly due to the relatively high levels in our
      population.

PMID- 17547712
TI  - Secular trends in cardiovascular risk factors: an age-period cohort analysis of
      698,954 health examinations in 181,350 Austrian men and women.
AB  - OBJECTIVES: It is well established that morbidity and mortality patterns in
      cardiovascular diseases vary strongly over time, yet the determinants of such
      trends remain poorly understood. To assess the potential contribution of secular
      or cross-generation patterns, we evaluated birth cohort-related trends across the
      20th century of risk factors in a large database of Austrian men and women.
      SUBJECTS AND SETTING: Trends in risk factors were investigated for 181,350 adults
      aged 20-79 years born between 1905 and 1975 undergoing 698,954 health
      examinations between 1985 and 2005 as participants of the Vorarlberg Health
      Monitoring and Promotion Programme. RESULTS: There was clear evidence of cohort
      related shifts in all risk factors. Total serum cholesterol and triglyceride
      declined markedly, particularly in the youngest cohorts, as did systolic and
      diastolic blood pressure in both men and women. By contrast, fasting glucose
      showed a strong rising tendency in both sexes and at all ages, most markedly in
      young males. Average glucose levels were between 4 and 15 mg dL(-1) higher in
      individuals at the same age born 20 years later. In males, body weight expressed
      in kg m(-2) (body mass index) was increasing as well; however, in women, patterns
      were most marked at the 90th percentile. CONCLUSION: These findings provide
      strong evidence of population wide secular shifts and suggest that in addition to
      period influences, most probably through treatment intervention and lifestyle
      change, determinants across the life-course are programming shifts from childhood
      onwards.

PMID- 17547713
TI  - Angiotensin converting enzyme inhibitor and angiotensin receptor blockade use in
      relation to outcomes in anticoagulated patients with atrial fibrillation.
AB  - BACKGROUND: The renin-angiotensin-aldosterone-system (RAAS) plays an important
      role in atrial fibrillation (AF). Evidence shows that blocking the RAAS with
      angiotensin converting enzyme inhibitors (ACEIs) and angiotensin receptor
      blockers (ARBs) has a definite role in preventing new onset AF and in maintaining
      sinus rhythm in recurrent AF. Our aim was to determine if ACEI/ARB treatment was
      associated with clinical outcomes [stroke/systemic embolic events (SEE),
      mortality] in a controlled, anticoagulated AF population. METHODS: An ancillary
      retrospective cross-sectional and longitudinal analysis of participants in the
      Stroke Prevention using an ORal Thrombin Inhibitor in AF (SPORTIF) III and V
      trials, in relation to use (or nonuse) of ACEI/ARBs. RESULTS: Rates of
      stroke/SEEs, mortality or major bleeding were no different between users and
      nonusers in the whole cohort, or in relation to the presence/absence of
      hypertension, coronary artery disease and previous stroke/transient ischaemic
      attack, nor amongst those aged <75 years. Patients aged > or = 75 years taking
      ACEIs or ARBs had lower mortality (HR 0.71, 95% CI 0.52-0.95), but no significant
      influence on other end-points was noted. Diabetics and those with left
      ventricular dysfunction on ximelagatran had a higher odds ratio of abnormal liver
      enzyme levels. There was no apparent benefit of ACEIs or ARBs on other event
      rates. CONCLUSIONS: This analysis from two large randomized trials of
      anticoagulation has not demonstrated a significant benefit of ACEI or ARB use
      amongst AF patients, except amongst elderly subjects.

PMID- 17547714
TI  - Increased formation of 8-iso-prostaglandin F(2alpha) is associated with altered
      bone metabolism and lower bone mass in hypercholesterolaemic subjects.
AB  - OBJECTIVES: To investigate the relationship of 8-iso-prostaglandin (PG) F(2alpha)
      levels, a reliable marker of in vivo oxidative stress and lipid peroxidation,
      with bone mineral density (BMD), bone turnover markers, osteoprotegerin (OPG) and
      receptor activator of nuclear factor-kappa B ligand (RANKL) in
      hypercholesterolaemia. DESIGN: Cross-sectional study. SETTING: University
      hospital centre. METHODS: Serum 8-iso-PGF(2alpha) levels were measured in 173
      hypercholesterolaemic subjects and in 152 age- and sex-matched
      normocholesterolaemic controls. Femoral neck and lumbar spine BMD, serum bone
      specific alkaline phosphatase (BAP), osteocalcin (OC), OPG and RANKL levels, as
      well as urinary levels of C-terminal telopeptides of type I collagen (CTX-I),
      were also assessed. RESULTS: Hypercholesterolaemic subjects showed higher (P <
      0.0001) serum 8-iso-PGF(2alpha) levels than controls. They also had decreased (P
      < 0.0001) femoral neck and lumbar spine BMD, and lower (P < 0.0001) serum BAP and
      OC levels. No significant differences between hypercholesterolaemic and control
      subjects were found when comparing urinary CTX-I levels, or serum OPG and RANKL
      levels. In multivariate linear regression analysis, serum 8-iso-PGF(2alpha) was
      the only negative predictor for femoral neck BMD and serum BAP and OC levels in
      hypercholesterolaemic subjects. No significant correlation (all P > 0.25) was
      present between serum 8-iso-PGF(2alpha) levels and urinary CTX-I levels, or serum
      OPG and RANKL levels, in hypercholesterolaemic subjects. CONCLUSIONS: We found an
      association between increased serum 8-iso-PGF(2alpha) levels and lower bone mass
      and reduced serum BAP and OC concentrations in hypercholesterolaemic subjects.
      These results would suggest a possible role for oxidative stress in the
      development of lower bone mass in hypercholesterolaemia.

PMID- 17547715
TI  - Validation of a clinical prognostic model to identify low-risk patients with
      pulmonary embolism.
AB  - OBJECTIVE: To validate the Pulmonary Embolism Severity Index (PESI), a clinical
      prognostic model which identifies low-risk patients with pulmonary embolism (PE).
      DESIGN: Validation study using prospectively collected data. SETTING: A total of
      119 European hospitals. SUBJECTS: A total of 899 patients diagnosed with PE.
      INTERVENTION: The PESI uses 11 clinical factors to stratify patients with PE into
      five classes (I-V) of increasing risk of mortality. We calculated the PESI risk
      class for each patient and the proportion of patients classified as low-risk
      (classes I and II). The outcomes were overall and PE-specific mortality for low
      risk patients at 3 months after presentation. We calculated the sensitivity,
      specificity and predictive values to predict overall and PE-specific mortality
      and the discriminatory power using the area under the receiver operating
      characteristic curve. RESULTS: Overall and PE-specific mortality was 6.5%
      (58/899) and 2.3% (21/899) respectively. Forty-seven per cent of patients
      (426/899) were classified as low-risk. Low-risk patients had an overall mortality
      of only 1.2% (5/426) and a PE-specific mortality of 0.7% (3/426). The sensitivity
      was 91 [95% confidence interval (CI): 81-97%] and the negative predictive value
      was 99% (95% CI: 97-100%) for overall mortality. The sensitivity was 86% (95% CI:
      64-97%) and the negative predictive value was 99% (95% CI: 98-100%) for PE
      specific mortality. The areas under the receiver operating characteristic curve
      for overall and PE-specific mortality were 0.80 (95% CI: 0.75-0.86) and 0.77 (95%
      CI: 0.68-0.86) respectively. CONCLUSIONS: This validation study confirms that the
      PESI reliably identifies low-risk patients with PE who are potential candidates
      for less costly outpatient treatment.

PMID- 17547716
TI  - Recurrent herpes simplex virus infection in a patient with autoimmune
      polyendocrinopathy-candidiasis-ectodermal dystrophy associated with L29P and IVS9
      1G>C compound heterozygous autoimmune regulator gene mutations.
AB  - Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) has
      characteristic clinical features with organ-specific autoimmune polyendocrine
      diseases and candidiasis, caused by the mutations of autoimmune regulator (AIRE)
      gene. Although almost all patients are complicated with mucocutaneous
      candidiasis, no apparent susceptibility to other infections has yet been
      reported. We herein report that a patient with APECED suffered from recurrent
      herpes simplex virus type 1 (HSV-1) infection after severe primary herpetic
      stomatitis, associated with sequential HSV-1 isolates of the same genomic
      profile, consistent with endogeneous recurrence. Thus, not only candidiasis but
      also HSV infection should receive more attention in patients with APECED, with
      treatment being administered accordingly.

PMID- 17547717
TI  - Establishment and characterization of a cell line (DEOC-1) originating from a
      human malignant melanoma of the skin.
AB  - A new human malignant melanoma cell line, designated DEOC-1, was established from
      the heel lesion of a 59-year-old man. This cell line has grown well for 84
      months. The monolayer, cultured cells are polygonal in shape, appear to be
      spindle-shaped cells or multipolar cells, and have a tendency to pile up without
      contact inhibition. The cells are aneuploid, and the modal chromosomal number is
      in the hyper-triploid range. The cells were transplanted into the subcutis of
      SCID mice and produced tumors resembling the original tumor. The DEOC-1 cells (1
      x 10(6)/5 mL) produced 5-S-cysteinyldopa (5-S-CD). The cells were not sensitive
      in vitro to any anticancer drug currently used for the treatment of malignant
      melanoma. Increases in both the protein and the transcriptional levels (mRNA) of
      multidrug resistance-related genes (multidrug resistance gene 1, multidrug
      resistance-associated protein 1 and lung resistance-related protein) were
      observed in DEOC-1 cells. The DEOC-1 cells are well characterized and are a very
      useful material for basic research of malignant melanoma.

PMID- 17547718
TI  - Characterization, anticancer drug susceptibility and atRA-induced growth
      inhibition of a novel cell line (HUMEMS) established from pleural effusion of
      alveolar rhabdomyosarcoma of breast tissue.
AB  - We recently established a cell line derived from pleural effusion from a 13-year
      old girl with primary alveolar rhabdomyosarcoma (RMS with a chromosomal
      translocation t[2;13]) in the breast tissue. The cell line was designated as
      HUMEMS. Cases of primary alveolar RMS swelling in the breast are extremely rare
      (about 0.2% of all RMSs). Therefore, the HUMEMS cell line is an important
      material for studying therapeutics for malignant tumors in children. The HUMEMS
      cell line we isolated consisted of two morphological subtypes. One type (SSN
      cells) is small in size and has a single nucleus. Another (LMN cells) is large in
      size and has two or more nuclei. Both SSN cells and LMN cells were
      immunohistochemically positive for desmin and slightly positive for myoglobin.
      Our data suggested LMN cells are well-differentiated SSN cells. Moreover, in some
      of the LMN cells, rapid cell contractions (1-5 times/10 sec) were observed. We
      investigated the anticancer drug susceptibility of the HUMEMS cell line with an
      oxygen electrode apparatus (Daikin, DOX-10, JPN) and effect of all-trans-retinoic
      acid (atRA) to the cell line. The atRA-treatment inhibited proliferation of the
      HUMEMS cells.

PMID- 17547719
TI  - Establishment and characterization of an IGSK-2 cell line derived from ascitic
      fluid of recurrent hCG and somatostatin secreted adenocarcinoma of the stomach.
AB  - We examined a 32-year-old Japanese man who was clinically diagnosed with gastric
      cancer, type 4, and histopathologically diagnosed with mucinous and poorly
      differentiated adenocarcinoma (mucinous > poorly) of the stomach. We successfully
      established and characterized a cell line (designated as IGSK-2) derived from the
      ascitic fluid of the patient with recurrent and cisplatin-resistant carcinoma.
      The IGSK-2 cells grew in multi-layered culture in culture dishes. The cells
      secreted 18 pg/mL somatostatin, 9.1 mIU/mL human chorionic gonadotrophin (hCG),
      8000 U/mL carbohydrate antigen 19-9 and 410 ng/mL carcinoembryonic antigen over 4
      days of culture. The population doubling time was approximately 83 h. The
      susceptibility test of anticancer drugs revealed that IGSK-2 cells were sensitive
      to Taxol, but were not sensitive to cisplatin, 5-fluorouracil and irinotecan.
      Immunohistochemical staining revealed that the IGSK-2 cells were positive against
      antihCG antibody and antiserotonin antibody, and negative against
      antisomatostatin antibody and antigastrin antibody.

PMID- 17547720
TI  - Nephrogenic systemic fibrosis: is any contrast safe in renal failure?

PMID- 17547721
TI  - Respiratory infectious disease: complacency with empiricism in the age of
      molecular science. We can do better!

PMID- 17547722
TI  - Neurology of Fabry disease.
AB  - BACKGROUND: Fabry disease has diverse neurological manifestations, many of which
      influence morbidity and quality of life. AIMS: The aim of the study was to
      document the clinical and subclinical neurological manifestations in a cohort of
      Australian patients with Fabry disease, using multiple clinical tools and a
      multidisciplinary approach. METHODS: Participants completed focused
      questionnaires and underwent clinical neurological examination, Neurocognitive
      testing using Mini Mental State Examination and Neuropsychiatry Unit Cognitive
      Screen, Quantitative Sensory Testing (QST), autonomic assessment using RR
      interval variation, intracranial magnetic resonance imaging (MRI) and audiology.
      In subsets of patients who had previously undergone QST and/or prospective serial
      quality-of-life assessments over the previous 5 years, results before and after
      enzyme replacement therapy were compared. RESULTS: Twenty hemizygotes and two
      heterozygotes were recruited. The age (mean +/- standard deviation (SD)) of male
      participants was 40.4 +/- 11.9 years (range 20-62 years); the women were aged
      between 20 and 56 years. Increasing age was strongly associated with increasing
      neurological disability. Clinical peripheral neuropathy predominantly affected
      thermal sensation in all patients, with variable involvement of pinprick and
      light touch. QST confirmed these findings. Clinical cerebellar tests were
      commonly abnormal: this has not been previously reported in the absence of
      symptomatic cerebrovascular disease. There was hearing loss was in 90% of
      patients and no patient older than 44 years had normal hearing. MRI lesion
      prevalence increased with age. Despite neurological complications being common,
      formal cognitive testing was basically normal. QST thresholds for pain showed a
      significant change after enzyme replacement therapy. CONCLUSIONS: Neurological
      complications in Fabry disease are common, complex and may be devastating. All
      patients studied had neurological involvement, with protean and diverse
      manifestations.

PMID- 17547723
TI  - Prevalence of thyroid disease in an older Australian population.
AB  - AIM: To determine the prevalence of thyroid disease in an older Australian
      population in a population-based cross-sectional study. BACKGROUND: Community
      living subjects, aged 49 years or older, in two Blue Mountains postcodes were
      invited to participate in an eye, nutrition and health study between 1997 and
      2000. METHODS: Three thousand five hundred and nine of the 4489 identified
      persons participated. Fifty-seven per cent of 3504 who completed questionnaires
      were women; their mean age was 66.8 years. Thyroid-stimulating hormone (TSH) was
      measured in 2665 subjects (76% of those completing the questionnaire). The main
      outcome measures were serum TSH and free thyroxine levels, serum lipids, urate
      and sugar levels and questionnaire responses. RESULTS: The prevalence of
      recognized thyroid disease (either self-reported history of thyroid disease or
      current thyroxine treatment) was 10% (95% confidence interval (CI) 8.9-11.1%). An
      additional 3.6% (95%CI 2.9-4.3%) of participants had unrecognized thyroid disease
      (abnormal TSH). The TSH was abnormal in 7.1% (95%CI 5.8-8.4%) of women and 3.7%
      (95%CI 2.6-4.8%) of men. Sixty-five per cent of those with an abnormal TSH did
      not report a history of thyroid disease, whereas 25% of those taking thyroxine
      replacement therapy had an abnormal TSH level. The prevalence of hypothyroidism
      increased with increasing age in women. The mean fasting cholesterol was 0.36
      mmol/L (95%CI 0.15-0.57) higher in hypothyroid subjects than in euthyroid
      subjects. CONCLUSION: Thyroid disease in older Australian women is relatively
      common and may be undiagnosed. Ongoing monitoring of patients on thyroxine
      replacement therapy is important, given that 25% of treated patients had an
      abnormal TSH.

PMID- 17547724
TI  - Diagnostic and prognostic utility of the serum free light chain assay in patients
      with AL amyloidosis.
AB  - BACKGROUND: Organ dysfunction in AL amyloidosis is related to the production and
      deposition of amyloidogenic monoclonal light chains. These pathological light
      chains can now be quantified using the recently developed serum free light chain
      assay. METHODS: We retrospectively reviewed 31 patients with AL amyloidosis to
      determine the frequency of abnormal free light chain assay results at diagnosis
      and whether changes in the serum free light chain assay predict outcome after
      therapy. RESULTS: An abnormal free light chain assay was found in 30 of 31
      patients (97%) at the time of diagnosis. In the subset of our patients who
      received treatment for AL amyloidosis, a >50% reduction of the pathological free
      light chain following treatment was shown to predict improved overall survival.
      In our series of analyses, achievement of greater magnitudes of reduction of the
      free light chain result did not appear to provide additional prognostic
      information, nor did the baseline free light chain result predict outcome.
      CONCLUSION: Our findings support the use of the free light chain assay in the
      diagnostic work-up of patients with suspected AL amyloidosis, and also as a
      sensitive biomarker of response to therapy.

PMID- 17547725
TI  - Clinical perspectives in lymphoma.
AB  - The classification of both Hodgkin's and non-Hodgkin's lymphomas continues to
      evolve. The current World Health Organization classification incorporates data
      derived from advances in our understanding of the pathogenesis of these disorders
      together with their distinguishing immunophenotypic, genotypic, clinical and
      histopathological characteristics. As outcomes have improved, the main emphasis
      of treatment has been to incorporate a risk-adapted approach to reduce long-term
      toxicity without sacrificing efficacy through the use of varying combinations of
      chemotherapy, radiotherapy and immunotherapy.

PMID- 17547726
TI  - Pulmonary arterial hypertension in systemic sclerosis: the need for early
      detection and treatment.
AB  - Pulmonary arterial hypertension (PAH) is an important cause of mortality in
      systemic sclerosis (SSc). The symptoms are non-specific and can be ascribed to
      other features of the disease, so it is often underrecognized until the late
      stages. Earlier treatment with new agents is associated with better treatment
      outcomes. The aim of this article is to develop evidence-based guidelines for
      screening for PAH and interstitial lung disease (ILD) in SSc. PAH occurs in up to
      27% of patients with SSc. Abnormal pulmonary function, particularly a
      disproportionate fall in carbon monoxide diffusing capacity (DLCO), can identify
      patients in the early stages of PAH, prompting further investigation in high-risk
      patients (limited SSc of >10 years' duration, symptoms and/or signs of PAH, DLCO
      <50% predicted, a rapid or large fall in DLCO without evidence of ILD and/or
      estimated systolic pulmonary artery pressure >45 mmHg on echocardiography). Right
      heart catheter remains the diagnostic gold standard. An algorithm for screening
      with regular pulmonary function tests for the early detection of PAH and ILD in
      SSc is proposed.

PMID- 17547727
TI  - Effect of long-term nebulized colistin on lung function and quality of life in
      patients with chronic bronchial sepsis.
AB  - Recurrent Gram-negative bacterial infection is a significant cause of death in
      patients with bronchiectasis and severe chronic obstructive pulmonary disease
      (COPD). Nebulized colistin in cystic fibrosis has shown maintenance of pulmonary
      function and improved symptom scores. We prospectively followed 18 patients with
      chronic bronchial sepsis treated with nebulized colistin 30 mg daily. Mean
      decline in forced expiratory volume in 1 s was significantly slower following
      commencement of inhaled colistin (44 mL/year vs 104 mL/year, P = 0.035). Mean
      decline in forced vital capacity was also significantly slower following
      commencement of colistin (48 mL/year vs 110 mL/year, P = 0.033). Patient-reported
      quality of life improved following commencement of colistin (3.6 vs 6.2, P =
      0.001). No patient had isolates resistant to colistin. No side-effects were
      reported by patients in the cohort. Use of inhaled colistin in the treatment of
      bronchiectasis and severe (COPD) in patients with recurrent Gram-negative
      infections is safe. Inhaled colistin may improve quality of life and slow decline
      in forced expiratory volume in 1 s and forced vital capacity.

PMID- 17547728
TI  - Tilt-test diagnosis of hypotensive transient ischaemic attacks.
AB  - Eight elderly patients with postural hypotension who presented with transient
      ischaemic attacks are reported. Six patients underwent head-up tilt testing with
      continuous blood pressure monitoring. During tilt, postural hypotension was found
      in five patients and in three patients transient ischaemic attacks were
      reproduced. Postural hypotension is probably a rare cause of transient ischaemic
      attacks, but may be underrecognized.

PMID- 17547729
TI  - Tripe palms or acanthosis palmaris.

PMID- 17547730
TI  - Cerebral dural arteriovenous fistulas presenting as pulsatile tinnitus.

PMID- 17547731
TI  - Non-traumatic kidney rupture in a tuberosclerosis patient with renal
      angiomyolipomas.

PMID- 17547732
TI  - Severe palmar-plantar erythema in a patient with breast cancer receiving
      doxorubicin-cyclophosphamide chemotherapy.

PMID- 17547733
TI  - Deep vein thrombosis occurring on treatment of patients receiving thalidomide
      with erythropoietin.

PMID- 17547734
TI  - Strong association between the use of gadolinium-based contrast agents with
      nephrogenic fibrosing dermopathy/nephrogenic systemic fibrosis.

PMID- 17547736
TI  - Management of infected pacemakers and implantable cardioverter-defibrillators.

PMID- 17547738
TI  - General practitioner referral letters: are we getting the full picture?

PMID- 17547739
TI  - Research degrees for medical graduates.

PMID- 17547740
TI  - A study of spatial resolution in pollution exposure modelling.
AB  - BACKGROUND: This study is part of several ongoing projects concerning
      epidemiological research into the effects on health of exposure to air pollutants
      in the region of Scania, southern Sweden. The aim is to investigate the optimal
      spatial resolution, with respect to temporal resolution, for a pollutant database
      of NOx-values which will be used mainly for epidemiological studies with
      durations of days, weeks or longer periods. The fact that a pollutant database
      has a fixed spatial resolution makes the choice critical for the future use of
      the database. RESULTS: The results from the study showed that the accuracy
      between the modelled concentrations of the reference grid with high spatial
      resolution (100 m), denoted the fine grid, and the coarser grids (200, 400, 800
      and 1600 meters) improved with increasing spatial resolution. When the pollutant
      values were aggregated in time (from hours to days and weeks) the disagreement
      between the fine grid and the coarser grids were significantly reduced. The
      results also illustrate a considerable difference in optimal spatial resolution
      depending on the characteristic of the study area (rural or urban areas). To
      estimate the accuracy of the modelled values comparison were made with measured
      NOx values. The mean difference between the modelled and the measured value were
      0.6 mug/m3 and the standard deviation 5.9 mug/m3 for the daily difference.
      CONCLUSION: The choice of spatial resolution should not considerably deteriorate
      the accuracy of the modelled NOx values. Considering the comparison between
      modelled and measured values we estimate that an error due to coarse resolution
      greater than 1 mug/m3 is inadvisable if a time resolution of one day is used.
      Based on the study of different spatial resolutions we conclude that for urban
      areas a spatial resolution of 200-400 m is suitable; and for rural areas the
      spatial resolution could be coarser (about 1600 m). This implies that we should
      develop a pollutant database that allows different spatial resolution for urban
      and rural areas.

PMID- 17547742
TI  - Characteristics of predictor sets found using differential prioritization.
AB  - BACKGROUND: Feature selection plays an undeniably important role in
      classification problems involving high dimensional datasets such as microarray
      datasets. For filter-based feature selection, two well-known criteria used in
      forming predictor sets are relevance and redundancy. However, there is a third
      criterion which is at least as important as the other two in affecting the
      efficacy of the resulting predictor sets. This criterion is the degree of
      differential prioritization (DDP), which varies the emphases on relevance and
      redundancy depending on the value of the DDP. Previous empirical works on
      publicly available microarray datasets have confirmed the effectiveness of the
      DDP in molecular classification. We now propose to establish the fundamental
      strengths and merits of the DDP-based feature selection technique. This is to be
      done through a simulation study which involves vigorous analyses of the
      characteristics of predictor sets found using different values of the DDP from
      toy datasets designed to mimic real-life microarray datasets. RESULTS: A
      simulation study employing analytical measures such as the distance between
      classes before and after transformation using principal component analysis is
      implemented on toy datasets. From these analyses, the necessity of adjusting the
      differential prioritization based on the dataset of interest is established. This
      conclusion is supported by comparisons against both simplistic rank-based
      selection and state-of-the-art equal-priorities scoring methods, which
      demonstrates the superiority of the DDP-based feature selection technique.
      Reapplying similar analyses to real-life multiclass microarray datasets provides
      further confirmation of our findings and of the significance of the DDP for
      practical applications. CONCLUSION: The findings have been achieved based on
      analytical evaluations, not empirical evaluation involving classifiers, thus
      providing further basis for the usefulness of the DDP and validating the need for
      unequal priorities on relevance and redundancy during feature selection for
      microarray datasets, especially highly multiclass datasets.

PMID- 17547741
TI  - Human Polycomb group EED protein negatively affects HIV-1 assembly and release.
AB  - BACKGROUND: The human EED protein, a member of the superfamily of Polycomb group
      (PcG) proteins with WD-40 repeats, has been found to interact with three HIV-1
      components, namely the structural Gag matrix protein (MA), the integrase enzyme
      (IN) and the Nef protein. The aim of the present study was to analyze the
      possible biological role of EED in HIV-1 replication, using the HIV-1-based
      vector HIV-Luc and EED protein expressed by DNA transfection of 293T cells.
      RESULTS: During the early phase of HIV-1 infection, a slight negative effect on
      virus infectivity occurred in EED-expressing cells, which appeared to be
      dependent on EED-MA interaction. At late times post infection, EED caused an
      important reduction of virus production, from 20- to 25-fold as determined by
      CAp24 immunoassay, to 10- to 80-fold based on genomic RNA levels, and this
      decrease was not due to a reduction of Gag protein synthesis. Coexpression of
      WTNef, or the non-N-myristoylated mutant NefG2A, restored virus yields to levels
      obtained in the absence of exogenous EED protein. This effect was not observed
      with mutant NefDelta57 mimicking the Nef core, or with the lipid raft-retargeted
      fusion protein LAT-Nef. LATAA-Nef, a mutant defective in the lipid raft
      addressing function, had the same anti-EED effect as WTNef. Cell fractionation
      and confocal imaging showed that, in the absence of Nef, EED mainly localized in
      membrane domains different from the lipid rafts. Upon co-expression with WTNef,
      NefG2A or LATAA-Nef, but not with NefDelta57 or LAT-Nef, EED was found to
      relocate into an insoluble fraction along with Nef protein. Electron microscopy
      of HIV-Luc producer cells overexpressing EED showed significant less virus
      budding at the cell surface compared to control cells, and ectopic assembly and
      clustering of nuclear pore complexes within the cytoplasm. CONCLUSION: Our data
      suggested that EED exerted an antiviral activity at the late stage of HIV-1
      replication, which included genomic RNA packaging and virus assembly, resulting
      possibly from a mistrafficking of viral genomic RNA (gRNA) or gRNA/Gag complex.
      Nef reversed the EED negative effect on virus production, a function which
      required the integrity of the Nef N-terminal domain, but not its N-myristoyl
      group. The antagonistic effect of Nef correlated with a cellular redistribution
      of both EED and Nef.

PMID- 17547743
TI  - Ellis-van Creveld syndrome.
AB  - Ellis-van Creveld syndrome (EVC) is a chondral and ectodermal dysplasia
      characterized by short ribs, polydactyly, growth retardation, and ectodermal and
      heart defects. It is a rare disease with approximately 150 cases reported
      worldwide. The exact prevalence is unknown, but the syndrome seems more common
      among the Amish community. Prenatal abnormalities (that may be detected by
      ultrasound examination) include narrow thorax, shortening of long bones,
      hexadactyly and cardiac defects. After birth, cardinal features are short
      stature, short ribs, polydactyly, and dysplastic fingernails and teeth. Heart
      defects, especially abnormalities of atrial septation, occur in about 60% of
      cases. Cognitive and motor development is normal. This rare condition is
      inherited as an autosomal recessive trait with variable expression. Mutations of
      the EVC1 and EVC2 genes, located in a head to head configuration on chromosome
      4p16, have been identified as causative. EVC belongs to the short rib-polydactyly
      group (SRP) and these SRPs, especially type III (Verma-Naumoff syndrome), are
      discussed in the prenatal differential diagnosis. Postnatally, the essential
      differential diagnoses include Jeune dystrophy, McKusick-Kaufman syndrome and
      Weyers syndrome. The management of EVC is multidisciplinary. Management during
      the neonatal period is mostly symptomatic, involving treatment of the respiratory
      distress due to narrow chest and heart failure. Orthopedic follow-up is required
      to manage the bones deformities. Professional dental care should be considered
      for management of the oral manifestations. Prognosis is linked to the respiratory
      difficulties in the first months of life due to thoracic narrowness and possible
      heart defects. Prognosis of the final body height is difficult to predict.

PMID- 17547744
TI  - Spatial analysis of colorectal cancer incidence and proportion of late-stage in
      Massachusetts residents: 1995-1998.
AB  - BACKGROUND: The aims of this study were to determine if observed geographic
      variations in colorectal cancer incidence are simply random or are statistically
      significant deviations from randomness, whether statistically significant
      excesses are temporary or persistent, and whether they can be explained by risk
      factors such as socioeconomic status (SES) or the percent of the population
      residing in an urban area rather than a rural area. Between 1995 and 1998, 6360
      male and 6628 female invasive colorectal cancer cases were diagnosed in
      Massachusetts residents. Cases were aggregated to Census tracts and analyzed for
      deviations from random occurrence with respect to both location and time.
      RESULTS: Six geographic areas that deviated significantly from randomness were
      uncovered in the age-adjusted analyses of males: three with higher incidence
      rates than expected and eight lower than expected. In the age-adjusted analyses
      of females, one area with a higher incidence rate, and one area with a lower
      incidence rate than expected, were found. After adjustment for SES and percent
      urban, some of these areas were no longer significantly different. CONCLUSION:
      Public health practitioners can use the results of this study to focus their
      attention onto areas in Massachusetts that need to increase colorectal screening
      or have elevated risk of colorectal cancer incidence.

PMID- 17547745
TI  - Interventions for increasing chlamydia screening in primary care: a review.
AB  - BACKGROUND: Despite guidelines recommending opportunistic chlamydia screening of
      younger women, screening rates in some countries remain low. Our aim was to
      review the evidence for specific interventions aimed at increasing chlamydia
      screening rates in primary care. METHODS: A Medline search was conducted for
      controlled trials that assessed the effectiveness of interventions aimed at
      improving chlamydia screening rates in primary health care settings. The Medline
      search was done for studies in English published prior to December 2005 using the
      following key words: chlamydia, screening, intervention, primary care and GPs. In
      addition, the references cited in the articles were reviewed. Studies in English
      published prior to December 2005 were reviewed. RESULTS: Four controlled studies
      met the inclusion criteria--3 were randomized studies and one was not. Strategies
      to increase screening rates included the use of educational packages targeting
      primary care physicians and the correction of barriers to screening within clinic
      systems. In 3 studies, the intervention was associated with an increase in
      screening rates of between 100% and 276% (p < 0.04). In the fourth study, the
      intervention was associated with a significant attenuation in declining screening
      rates over time (4% versus 34% decline, p = 0.04). CONCLUSION: There are only a
      limited number of randomized or controlled studies that demonstrate improved
      chlamydia screening of younger women in primary care.

PMID- 17547746
TI  - Morbidity associated with systemic corticosteroid preparation for coronary artery
      bypass grafting in patients with chronic obstructive pulmonary disease: a case
      control study.
AB  - BACKGROUND: Coronary artery bypass grafting (CABG) is associated with high
      morbidity in patients with chronic obstructive pulmonary disease (COPD).We
      examine the effect of preoperative systemic corticosteroids on morbidity in this
      setting. METHODS: Ninety candidates for elective CABG participated in a
      prospective, open randomized trial, including 30 patients with COPD who received
      a single injection of a long-acting corticosteroid, 30 with COPD who received
      placebo, and 30 without COPD who served as controls. Primary end-points were
      postoperative pulmonary and nonpulmonary complications. Secondary end-points were
      length of hospital stay (LOS), ICU stay of less than 24 hours and more than 48
      hours, duration of mechanical ventilation, and time to walking and sitting.
      RESULTS: The rate of pulmonary complications was similar in the two COPD groups
      and in the COPD patients and controls. The placebo group had more major
      nonpulmonary complications than the treatment group, but the difference was not
      statistically significant (26% vs. 17%, P = NS). The non-COPD control group had
      significantly fewer nonpulmonary complications than the COPD patients
      (treatment+placebo) (33% vs 70%, P = 0.014) and a similar rate of pulmonary
      complications. There was a statistically significant difference between the
      treated and placebo COPD groups in ICU stay less than 24 hours (P < or = 0.001)
      and more than 48 hours (P = 0.03) and hospital stay (P = 0.013). On stepwise
      analysis, only age and number of coronary grafts were predictors of pulmonary
      complications. CONCLUSION: The use of preoperative systemic corticosteroids in
      patients with COPD undergoing CABG may shorten ICU and hospital stay.

PMID- 17547747
TI  - Mixture modeling of transcript abundance classes in natural populations.
AB  - BACKGROUND: Populations diverge in genotype and phenotype under the influence of
      such evolutionary processes as genetic drift, mutation accumulation, and natural
      selection. Because genotype maps onto phenotype by way of transcription, it is of
      interest to evaluate how these evolutionary factors influence the structure of
      variation at the level of transcription. Here, we explore the distributions of
      cis-acting and trans-acting factors and their relative contributions to
      expression of transcripts that exhibit two or more classes of abundance among
      individuals within populations. RESULTS: Expression profiling using cDNA
      microarrays was conducted in Drosophila melanogaster adult female heads for 58
      nearly isogenic lines from a North Carolina population and 50 from a California
      population. Using a mixture modeling approach, transcripts were identified that
      exhibit more than one mode of transcript abundance across the samples. Power
      studies indicate that sample sizes of 50 individuals will generally be sufficient
      to detect divergent transcript abundance classes. The distribution of transcript
      abundance classes is skewed toward low frequency minor classes, which is
      reminiscent of the typical skew in genotype frequencies. Similar results are
      observed in reported data on gene expression in human lymphoblast cell lines, in
      which analysis of association with linked polymorphisms implies that cis-acting
      single nucleotide polymorphisms make only a modest contribution to bimodal
      distributions of transcript abundance. CONCLUSION: Population surveys of gene
      expression may complement genetical genomics as a general approach to quantifying
      sources of transcriptional variation. Differential expression of transcripts
      among individuals is due to a complex interplay of cis-acting and trans-acting
      factors.

PMID- 17547748
TI  - Did an ancient chlamydial endosymbiosis facilitate the establishment of primary
      plastids?
AB  - BACKGROUND: Ancient endosymbioses are responsible for the origins of mitochondria
      and plastids, and they contribute to the divergence of several major eukaryotic
      groups. Although chlamydiae, a group of obligate intracellular bacteria, are not
      found in plants, an unexpected number of chlamydial genes are most similar to
      plant homologs, which, interestingly, often contain a plastid-targeting signal.
      This observation has prompted several hypotheses, including gene transfer between
      chlamydiae and plant-related groups and an ancestral relationship between
      chlamydiae and cyanobacteria. RESULTS: We conducted phylogenomic analyses of the
      red alga Cyanidioschyzon merolae to identify genes specifically related to
      chlamydial homologs. We show that at least 21 genes were transferred between
      chlamydiae and primary photosynthetic eukaryotes, with the donor most similar to
      the environmental Protochlamydia. Such an unusually high number of transferred
      genes suggests an ancient chlamydial endosymbiosis with the ancestral primary
      photosynthetic eukaryote. We hypothesize that three organisms were involved in
      establishing the primary photosynthetic lineage: the eukaryotic host cell, the
      cyanobacterial endosymbiont that provided photosynthetic capability, and a
      chlamydial endosymbiont or parasite that facilitated the establishment of the
      cyanobacterial endosymbiont. CONCLUSION: Our findings provide a glimpse into the
      complex interactions that were necessary to establish the primary endosymbiotic
      relationship between plastid and host cytoplasms, and thereby explain the rarity
      with which long-term successful endosymbiotic relationships between heterotrophs
      and photoautotrophs were established. Our data also provide strong and
      independent support for a common origin of all primary photosynthetic eukaryotes
      and of the plastids they harbor.

PMID- 17547749
TI  - Role of stem cells in cancer therapy and cancer stem cells: a review.
AB  - For over 30 years, stem cells have been used in the replenishment of blood and
      immune systems damaged by the cancer cells or during treatment of cancer by
      chemotherapy or radiotherapy. Apart from their use in the immuno-reconstitution,
      the stem cells have been reported to contribute in the tissue regeneration and as
      delivery vehicles in the cancer treatments. The recent concept of 'cancer stem
      cells' has directed scientific communities towards a different wide new area of
      research field and possible potential future treatment modalities for the cancer.
      Aim of this review is primarily focus on the recent developments in the use of
      the stem cells in the cancer treatments, then to discuss the cancer stem cells,
      now considered as backbone in the development of the cancer; and their role in
      carcinogenesis and their implications in the development of possible new cancer
      treatment options in future.

PMID- 17547750
TI  - A new advance in alternative splicing databases: from catalogue to detailed
      analysis of regulation of expression and function of human alternative splicing
      variants.
AB  - BACKGROUND: Most human genes produce several transcripts with different exon
      contents by using alternative promoters, alternative polyadenylation sites and
      alternative splice sites. Much effort has been devoted to describing known gene
      transcripts through the development of numerous databases. Nevertheless, owing to
      the diversity of the transcriptome, there is a need for interactive databases
      that provide information about the potential function of each splicing variant,
      as well as its expression pattern. DESCRIPTION: After setting up a database in
      which human and mouse splicing variants were compiled, we developed tools (1) to
      predict the production of protein isoforms from these transcripts, taking account
      of the presence of open reading frames and mechanisms that could potentially
      eliminate transcripts and/or inhibit their translation, i.e. nonsense-mediated
      mRNA decay and microRNAs; (2) to support studies of the regulation of transcript
      expression at multiple levels, including transcription and splicing, particularly
      in terms of tissue specificity; and (3) to assist in experimental analysis of the
      expression of splicing variants. Importantly, analyses of all features from
      transcript metabolism to functional protein domains were integrated in a highly
      interactive, user-friendly web interface that allows the functional and
      regulatory features of gene transcripts to be assessed rapidly and accurately.
      CONCLUSION: In addition to identifying the transcripts produced by human and
      mouse genes, fast DB http://www.fast-db.com provides tools for analyzing the
      putative functions of these transcripts and the regulation of their expression.
      Therefore, fast DB has achieved an advance in alternative splicing databases by
      providing resources for the functional interpretation of splicing variants for
      the human and mouse genomes. Because gene expression studies are increasingly
      employed in clinical analyses, our web interface has been designed to be as user
      friendly as possible and to be readily searchable and intelligible at a glance by
      the whole biomedical community.

PMID- 17547751
TI  - Cystic fibrosis and renal disease: a case report.
AB  - BACKGROUND: Cystic fibrosis (CF) is an autosomal recessive disease that is
      predominantly seen in the Caucasian population and involves multiple organs.
      Traditionally it has been thought that the kidney is the only organ which does
      not seem to be generally affected by the disease although the cystic fibrosis
      transmembrane conductance regulator (CFTR) gene is expressed in the kidney. CASE
      PRESENTATION: We report the case of an 11 year old boy with cystic fibrosis and
      nephrotic syndrome and review the literature that describes nephrotic syndrome
      and renal involvement in cystic fibrosis. CONCLUSION: With continued advances in
      the management of cystic fibrosis and improvement in life expectancy, several
      unrecognized co-morbidities are expected to emerge. It is important to screen
      patients for possible co-morbidities. Urine analysis may be helpful in this group
      of patients and any proteinuria should raise the suspicion of cystic fibrosis
      related renal disease.

PMID- 17547752
TI  - Pediatricians' attitudes, experience and referral patterns regarding
      Complementary/Alternative Medicine: a national survey.
AB  - BACKGROUND: To assess pediatricians' attitudes toward & practice of
      Complementary/Alternative Medicine (CAM) including their knowledge, experience, &
      referral patterns for CAM therapies. METHODS: An anonymous, self-report, 27-item
      questionnaire was mailed nationally to fellows of the American Academy of
      Pediatrics in July 2004.648 of 3500 pediatricians' surveyed responded (18%).
      RESULTS: The median age ranged from 46-59 yrs; 52% female, 81% Caucasian, 71%
      generalists, & 85% trained in the US. Over 96% of pediatricians' responding
      believed their patients were using CAM. Discussions of CAM use were initiated by
      the family (70%) & only 37% of pediatricians asked about CAM use as part of
      routine medical history. Majority (84%) said more CME courses should be offered
      on CAM and 71% said they would consider referring patients to CAM practitioners.
      Medical conditions referred for CAM included; chronic problems (headaches, pain
      management, asthma, backaches) (86%), diseases with no known cure (55.5%) or
      failure of conventional therapies (56%), behavioral problems (49%), & psychiatric
      disorders (47%). American born, US medical school graduates, general
      pediatricians, & pediatricians who ask/talk about CAM were most likely to believe
      their patients used CAM (P < 0.01). CONCLUSION: Pediatricians' have a positive
      attitude towards CAM. Majority believe that their patients are using CAM, that
      asking about CAM should be part of routine medical history, would consider
      referring to a CAM practitioner and want more education on CAM.

PMID- 17547753
TI  - Time variations in the transmissibility of pandemic influenza in Prussia,
      Germany, from 1918-19.
AB  - BACKGROUND: Time variations in transmission potential have rarely been examined
      with regard to pandemic influenza. This paper reanalyzes the temporal
      distribution of pandemic influenza in Prussia, Germany, from 1918-19 using the
      daily numbers of deaths, which totaled 8911 from 29 September 1918 to 1 February
      1919, and the distribution of the time delay from onset to death in order to
      estimate the effective reproduction number, Rt, defined as the actual average
      number of secondary cases per primary case at a given time. RESULTS: A discrete
      time branching process was applied to back-calculated incidence data, assuming
      three different serial intervals (i.e. 1, 3 and 5 days). The estimated
      reproduction numbers exhibited a clear association between the estimates and
      choice of serial interval; i.e. the longer the assumed serial interval, the
      higher the reproduction number. Moreover, the estimated reproduction numbers did
      not decline monotonically with time, indicating that the patterns of secondary
      transmission varied with time. These tendencies are consistent with the
      differences in estimates of the reproduction number of pandemic influenza in
      recent studies; high estimates probably originate from a long serial interval and
      a model assumption about transmission rate that takes no account of time
      variation and is applied to the entire epidemic curve. CONCLUSION: The present
      findings suggest that in order to offer robust assessments it is critically
      important to clarify in detail the natural history of a disease (e.g. including
      the serial interval) as well as heterogeneous patterns of transmission. In
      addition, given that human contact behavior probably influences transmissibility,
      individual countermeasures (e.g. household quarantine and mask-wearing) need to
      be explored to construct effective non-pharmaceutical interventions.

PMID- 17547754
TI  - t(8;14;18): a 3-way chromosome translocation in two patients with Burkitt's
      lymphoma/leukemia.
AB  - Burkitt's lymphoma (BL) is a heterogeneous group of highly aggressive mature B
      cell malignancies. It is characterized by a high rate of turnover of malignant
      cells and deregulation of the c-myc gene. It is typically associated with a
      t(8;14) translocation. Dual translocation of t(8;14) (c-myc) and t(14;18) (bcl-2)
      was reported to be associated with extremely poor prognosis. This study reports a
      novel t(8;14;18) triple translocation in two patients with Burkitt's lymphoma.

PMID- 17547755
TI  - Testicular involution prior to sex change in gilthead seabream is characterized
      by a decrease in DMRT1 gene expression and by massive leukocyte infiltration.
AB  - BACKGROUND: Leukocytes are found within the testis of most, if not all, mammals
      and are involved in immunological surveillance, physiological regulation and
      tissue remodelling. The testis of seasonal breeding fish undergoes a regression
      process. In the present study, the second reproductive cycle (RC) of the
      protandrous seasonal teleost fish, gilthead seabream, was investigated and the
      presence of leukocytes analysed. Special attention has been paid to the
      testicular degenerative process which is particularly active in the last stage of
      the second RC probably due to the immediacy of the sex change process. METHODS:
      Sexually mature specimens (n = 10-18 fish/month) were sampled during the second
      RC. Some specimens were intraperitoneally injected with bromodeoxyuridin (BrdU)
      before sampling. Light and electron microscopy was used to determine the
      different stages of gonadal development and the presence of leukocytes and PCR
      was used to analyse the gene expression of a testis-differentiating gene and of
      specific markers for macrophages and B and T lymphocytes. Immunocytochemistry and
      flow cytometry were performed using a specific antibody against acidophilic
      granulocytes from the gilthead seabream. Cell proliferation was detected by
      immunocytochemistry using an anti-BrdU antibody and apoptotic cells by in situ
      detection of DNA fragmentation. RESULTS: The fish in the western Mediterranean
      area developed as males during the first two RCs. The testis of all the specimens
      during the second RC underwent a degenerative process, which started at post
      spawning and was enhanced during the testicular involution stage, when
      vitellogenic oocytes appeared in the ovary accompanied by a progressive increase
      in the ovarian index. However, only 40% of specimens were females in the third
      RC. Leukocytes (acidophilic granulocytes, macrophages and lymphocytes) were
      present in the gonad and acidophilic granulocyte infiltration occurred during the
      last two stages. At the same time DMRT1 gene expression decreased. CONCLUSIONS:
      The results demonstrate that innate and adaptive immune cells are present in the
      gonads of gilthead seabream. Moreover, the whole fish population underwent a
      testicular degenerative process prior to sex change, characterized by high rates
      of apoptosis and necrosis and accompanied by an infiltration of acidophilic
      granulocytes and a decrease in DMRT1 levels.

PMID- 17547756
TI  - Conservation of the links between gene transcription and chromosomal organization
      in the highly reduced genome of Buchnera aphidicola.
AB  - BACKGROUND: Genomic studies on bacteria have clearly shown the existence of
      chromosomal organization as regards, for example, to gene localization, order and
      orientation. Moreover, transcriptomic analyses have demonstrated that, in free
      living bacteria, gene transcription levels and chromosomal organization are
      mutually influenced. We have explored the possible conservation of relationships
      between mRNA abundances and chromosomal organization in the highly reduced genome
      of Buchnera aphidicola, the primary endosymbiont of the aphids, and a close
      relative to Escherichia coli. RESULTS: Using an oligonucleotide-based microarray,
      we normalized the transcriptomic data by genomic DNA signals in order to have
      access to inter-gene comparison data. Our analysis showed that mRNA abundances,
      gene organization (operon) and gene essentiality are correlated in Buchnera
      (i.e., the most expressed genes are essential genes organized in operons) whereas
      no link between mRNA abundances and gene strand bias was found. The effect of
      Buchnera genome evolution on gene expression levels has also been analysed in
      order to assess the constraints imposed by the obligate symbiosis with aphids,
      underlining the importance of some gene sets for the survival of the two
      partners. Finally, our results show the existence of spatial periodic
      transcriptional patterns in the genome of Buchnera. CONCLUSION: Despite an
      important reduction in its genome size and an apparent decay of its capacity for
      regulating transcription, this work reveals a significant correlation between
      mRNA abundances and chromosomal organization of the aphid-symbiont Buchnera.

PMID- 17547757
TI  - Long-term maintenance of increased exercise involvement following a self
      management intervention for housebound older adults with arthritis.
AB  - BACKGROUND: Sustained maintenance of health behaviors is a determinant of
      successful symptom reduction strategies for older adults with arthritis. This
      study examined whether or not short-term improvements in exercise involvement
      were maintained 8 months following a home-based arthritis self-management
      intervention as well as the moderating role of individual characteristics in the
      maintenance of behavior change. METHODS: Of the 113 housebound older adult
      participants at pre-intervention, 97 completed the post-intervention interview,
      and 80 completed the 8-month post-intervention interview. RESULTS: Some post
      intervention improvements in exercise involvement were maintained 8 months later.
      More specifically, weekly exercise frequency, particularly regarding walking
      frequency, and variety of exercise activities were still significantly greater in
      the experimental group than in the control group 8 months following the
      completion of the intervention. No moderating influences were observed for any of
      the individual characteristics. CONCLUSION: We conclude that gains in exercise
      involvement achieved through a self-management intervention can be maintained 8
      months following the intervention.

PMID- 17547758
TI  - Developmental variations in plasma leptin, leptin soluble receptor and their
      molar ratio in healthy infants.
AB  - BACKGROUND: Leptin and its soluble receptor (sOB-R) are important to regulation
      of body composition but there are no data on the developmental variations in
      these plasma variables and their relationship with body composition measurements,
      METHODS: Weight, length, and body composition (bone, fat and lean mass) by dual
      energy absorptiometry, and plasma variables were measured in healthy infants at
      2, 4, 8 and 12 months. RESULTS: 15 whites and 29 African Americans (21 males and
      23 females) with mean birth weight 3357 +/- 45 (SEM) g and gestation of 39.3 +/-
      0.17 weeks were studied. The overall Z score for weight, length and weight for
      length during the study were 0.00 +/- 0.15, -0.08 +/- 0.11 and 0.12 +/- 0.14
      respectively. With increasing age, plasma leptin (1.0 to 18.2, median 5.5 ng/mL)
      and sOB-R:leptin molar ratio (10.1 to 247.4, median 59.9) were lowered (r = 
      0.47, p < 0.01; and r = -0.37, p < 0.05 respectively), best predicted by weight Z
      score and percentage of fat mass, and higher in African American and female.
      Presence of body composition measurements eliminated the race and gender effect
      on the plasma variables. Plasma sOB-R (49.5 to 173.9, median 81.3 ng/mL) did not
      change significantly with age and was correlated and predicted only by body
      composition measurements. CONCLUSION: In healthy growing infants, plasma leptin
      but not sOB-R decreases with age. Gender, race and anthropometric measurements
      are additional physiological determinants predictive of plasma leptin and the
      receptor:ligand ratio. However, body composition is the only variable that can
      predict plasma leptin and its soluble receptor and the receptor: ligand ratio;
      and body composition measurements eliminated the race and gender effect on these
      plasma variables.

PMID- 17547759
TI  - Antisense RNA directed to the human papillomavirus type 16 E7 mRNA from herpes
      simplex virus type 1 derived vectors is expressed in CaSki cells and
      downregulates E7 mRNA.
AB  - BACKGROUND: Human papillomavirus (HPV) infection is known to be the most
      important etiologic factor of cervical cancer. There is no HPV specific therapy
      available for treatment of invasive squamous cell carcinoma of the cervix and its
      precursor lesions. The present study elucidates the potential to use herpes
      simplex virus (HSV) derived vectors for expression of antisense RNA to HPV -16 E7
      oncogene. RESULTS: We have constructed replication competent, nonneuroinvasive
      HSV-1 vectors, deleted of the gamma134.5 gene. The vectors express RNA antisense
      to the first 100 nucleotides of the HPV-16 E7 gene. We assayed the ability of the
      antisense E7 vectors R5225 (tk-) and R5226 (tk+), to produce antisense RNA, as
      well as the consequent effects on E7 mRNA and protein levels in HPV-16 positive
      CaSki cells. Anti-E7 RNA was expressed by both constructs in a dose-dependent
      manner. Expression of HPV-16 E7 mRNA was downregulated effectively in CaSki cells
      infected with the tk- recombinant R5225 or with R5226. The tk+ recombinant R5226
      was effective in downregulating E7 protein expression. CONCLUSION: We have shown
      that anti-E7 RNA expressed from an HSV vector could efficiently downregulate HPV
      16 E7 mRNA and E7 protein expression in CaSki cells. We conclude that HSV vectors
      may become a useful tool for gene therapy of HPV infections.

PMID- 17547760
TI  - Implementing a guideline for the treatment of type 2 diabetics: results of a
      cluster-randomized controlled trial (C-RCT).
AB  - BACKGROUND: In Italy many diabetics still lack adequate care in general practice.
      We assessed the effectiveness of different strategies for the implementation of
      an evidence-based guideline for the management of non-complicated type 2 diabetes
      among General Practitioners (GPs) of Lazio region. METHODS: Three-arm cluster
      randomised controlled trial with GPs as units of randomisation (clusters). 252
      GPs were randomised either to an active strategy (training module with
      administration of the guideline), or to a passive dissemination (administration
      of the guideline only), or to usual care (control). Data on prescriptions of
      tests and drugs were collected by existing information systems, whereas patients'
      data came from GPs' databases. Process outcomes were measured at the cluster
      level one year after the intervention. Primary outcomes concerned the measurement
      of glycosilated haemoglobin and the commissioning of micro- and macrovascular
      complications assessment tests. In order to assess the physicians' drug
      prescribing behaviour secondary outcomes were also calculated. RESULTS: GPs
      identified 6395 uncomplicated type 2 patients with a high prevalence of
      cardiovascular risk factors. Data on GPs baseline performance show low
      proportions of glycosilated haemoglobin assessments. Results of the C-RCT
      analysis indicate that the active implementation strategy was ineffective
      relating to all primary outcomes (respectively, OR 1.06 [95% IC: 0.76-1.46]; OR
      1.07 [95% IC: 0.80-1.43]; OR 1.4 [95% IC:0.91-2.16]. Similarly, passive
      dissemination of the guideline showed no effect. CONCLUSION: In our region
      compliance of GPs with guidelines was not enhanced by a structured learning
      programme. Implementation through organizational measures appears to be essential
      to induce behavioural changes. TRIAL REGISTRATION: ISRCTN80116232.

PMID- 17547761
TI  - Comprehensive EST analysis of Atlantic halibut (Hippoglossus hippoglossus), a
      commercially relevant aquaculture species.
AB  - BACKGROUND: An essential first step in the genomic characterisation of a new
      species, in this case Atlantic halibut (Hippoglossus hippoglossus), is the
      generation of EST information. This forms the basis for subsequent microarray
      design, SNP detection and the placement of novel markers on genetic linkage maps.
      RESULTS: Normalised directional cDNA libraries were constructed from five
      different larval stages (hatching, mouth-opening, midway to metamorphosis,
      premetamorphosis, and post-metamorphosis) and eight different adult tissues
      (testis, ovary, liver, head kidney, spleen, skin, gill, and intestine).
      Recombination efficiency of the libraries ranged from 91-98% and insert size
      averaged 1.4 kb. Approximately 1000 clones were sequenced from the 5'-end of each
      library and after trimming, 12675 good sequences were obtained. Redundancy within
      each library was very low and assembly of the entire EST collection into contigs
      resulted in 7738 unique sequences of which 6722 (87%) had matches in Genbank.
      Removal of ESTs and contigs that originated from bacteria or food organisms
      resulted in a total of 7710 unique halibut sequences. CONCLUSION: A Unigene
      collection of 7710 functionally annotated ESTs has been assembled from Atlantic
      halibut. These have been incorporated into a publicly available, searchable
      database and form the basis for an oligonucleotide microarray that can be used as
      a tool to study gene expression in this economically important aquacultured fish.

PMID- 17547762
TI  - Increased platelet expression of FcGammaRIIa and its potential impact on platelet
      reactivity in patients with end stage renal disease.
AB  - BACKGROUND: Increased platelet reactivity has been implicated in cardiovascular
      disease - the major cause of death in patients with end stage renal disease
      (ESRD). FcGammaRIIA is a component of glycoprotein VI and Ib-IX-V that mediate
      activation of platelets by collagen and von Willebrand factor. To determine
      whether expression of FcGammaRIIA impacts platelet reactivity we quantified its
      expression and platelet reactivity in 33 patients with ESRD who were undergoing
      hemodialysis. METHODS: Blood samples were obtained from patients immediately
      before hemodialysis and before administration of heparin. Platelet expression of
      FcGammaRIIA and the activation of platelets in response to low concentrations of
      convulxin (1 ng/ml, selected to mimic effects of collagen), thrombin (1 nM),
      adenosine diphosphate (ADP, 0.2 microM), or platelet activating factor (PAF, 1
      nM) were determined with the use of flow cytometry in samples of whole blood
      anticoagulated with corn trypsin inhibitor (a specific inhibitor of Factor XIIa).
      RESULTS: Patients were stratified with respect to the median expression of
      FcGammaRIIA. Patients with high platelet expression of FcGammaRIIA exhibited 3
      fold greater platelet reactivity compared with that in those with low expression
      in response to convulxin (p < 0.01) and 2-fold greater activation in response to
      thrombin, ADP, and PAF (p < 0.05 for each). For each agonist, expression of
      FcGammaRIIA correlated modestly but positively with platelet reactivity. The
      strongest correlation was with thrombin-induced activation (r = 0.6, p < 0.001).
      CONCLUSION: Increased platelet reactivity in response to low concentrations of
      diverse agonists is associated with high expression of FcGammaRIIA and may
      contribute to an increased risk of thrombosis in patients with ESRD.

PMID- 17547763
TI  - Efficient replication of pneumonia virus of mice (PVM) in a mouse macrophage cell
      line.
AB  - Pneumonia virus of mice (PVM; family Paramyxoviridae, subfamily Pneumovirinae) is
      a natural respiratory pathogen of rodent species and an important new model for
      the study of severe viral bronchiolitis and pneumonia. However, despite high
      virus titers typically detected in infected mouse lung tissue in vivo, cell lines
      used routinely for virus propagation in vitro are not highly susceptible to PVM
      infection. We have evaluated several rodent and primate cell lines for
      susceptibility to PVM infection, and detected highest virus titers from infection
      of the mouse monocyte-macrophage RAW 264.7 cell line. Additionally, virus
      replication in RAW 264.7 cells induces the synthesis and secretion of
      proinflammatory cytokines relevant to respiratory virus disease, including tumor
      necrosis factor-alpha (TNF-alpha), interferon-beta (IFN-beta), macrophage
      inflammatory proteins 1alpha and 1beta (MIP-1alpha and MIP-1beta) and the
      functional homolog of human IL-8, mouse macrophage inflammatory peptide-2 (MIP
      2). Identification and characterization of a rodent cell line that supports the
      replication of PVM and induces the synthesis of disease-related proinflammatory
      mediators will facilitate studies of molecular mechanisms of viral pathogenesis
      that will complement and expand on findings from mouse model systems.

PMID- 17547765
TI  - Traditional medicinal plant knowledge and use by local healers in Sekoru
      District, Jimma Zone, Southwestern Ethiopia.
AB  - The knowledge and use of medicinal plant species by traditional healers was
      investigated in Sekoru District, Jimma Zone, Southwestern Ethiopia from December
      2005 to November 2006. Traditional healers of the study area were selected
      randomly and interviewed with the help of translators to gather information on
      the knowledge and use of medicinal plants used as a remedy for human ailments in
      the study area. In the current study, it was reported that 27 plant species
      belonging to 27 genera and 18 families were commonly used to treat various human
      ailments. Most of these species (85.71%) were wild and harvested mainly for their
      leaves (64.52%). The most cited ethnomedicinal plant species was Alysicarpus
      quartinianus A. Rich., whose roots and leaves were reported by traditional
      healers to be crushed in fresh and applied as a lotion on the lesions of patients
      of Abiato (Shererit). No significant correlation was observed between the age of
      traditional healers and the number of species reported and the indigenous
      knowledge transfer was found to be similar. More than one medicinal plant species
      were used more frequently than the use of a single species for remedy
      preparations. Plant parts used for remedy preparations showed significant
      difference with medicinal plant species abundance in the study area.

PMID- 17547764
TI  - Genetic flux over time in the Salmonella lineage.
AB  - BACKGROUND: DNA sequences that are shared between closely related organisms while
      being absent from their common ancestor and from sister lineages of that ancestor
      are likely to have been acquired by horizontal gene transfer. Over time, the
      composition of those sequences tends to become more similar to the compositional
      signature of their host (amelioration). RESULTS: From a whole-genome comparative
      analysis of eleven Salmonella, three Escherichia coli and one Shigella strain, we
      inferred the relative time of insertion of putative horizontally acquired (PHA)
      genes in three Salmonella strains on different branches of the S. enterica
      phylogenetic tree. Compositional analysis suggests that most of the PHA genes are
      still undergoing an amelioration process and shows a clear correlation between
      time of insertion and the level of amelioration. CONCLUSION: The results show
      that older insertions include almost all functional classes. However, very recent
      horizontal transfer events in the Salmonella lineage involve primarily prophage
      elements that are shared only between very recently diverged lineages; despite
      this, the prophage sequence composition is close to that of the host, indicating
      that host adaptation, rather than amelioration, is likely to be the source of the
      compositional similarity. Almost half of the PHA genes were acquired at the base
      of the Salmonella lineage, whereas nearly three-quarters are shared between most
      S. enterica subspecies. The numerical distribution of PHA genes in the Salmonella
      tree topology correlates well with the divergence of the major Salmonella
      species, highlighting the major impact of horizontal transfer on the evolution of
      the salmonellae.

PMID- 17547766
TI  - Construction and characterization of a full-length cDNA library for the wheat
      stripe rust pathogen (Puccinia striiformis f. sp. tritici).
AB  - BACKGROUND: Puccinia striiformis is a plant pathogenic fungus causing stripe
      rust, one of the most important diseases on cereal crops and grasses worldwide.
      However, little is know about its genome and genes involved in the biology and
      pathogenicity of the pathogen. We initiated the functional genomic research of
      the fungus by constructing a full-length cDNA and determined functions of the
      first group of genes by sequence comparison of cDNA clones to genes reported in
      other fungi. RESULTS: A full-length cDNA library, consisting of 42,240 clones
      with an average cDNA insert of 1.9 kb, was constructed using urediniospores of
      race PST-78 of P. striiformis f. sp. tritici. From 196 sequenced cDNA clones, we
      determined functions of 73 clones (37.2%). In addition, 36 clones (18.4%) had
      significant homology to hypothetical proteins, 37 clones (18.9%) had some
      homology to genes in other fungi, and the remaining 50 clones (25.5%) did not
      produce any hits. From the 73 clones with functions, we identified 51 different
      genes encoding protein products that are involved in amino acid metabolism, cell
      defense, cell cycle, cell signaling, cell structure and growth, energy cycle,
      lipid and nucleotide metabolism, protein modification, ribosomal protein complex,
      sugar metabolism, transcription factor, transport metabolism, and
      virulence/infection. CONCLUSION: The full-length cDNA library is useful in
      identifying functional genes of P. striiformis.

PMID- 17547767
TI  - Quality of life of adult retinoblastoma survivors in the Netherlands.
AB  - BACKGROUND: To assess the quality of life (QoL) and predictors thereof in Dutch
      adult hereditary and non-hereditary retinoblastoma (RB) survivors. METHODS: In
      this population-based cross-sectional study, a generic QoL questionnaire (SF-36)
      and a disease-specific interview were administered to 87 adult RB survivors aged
      18 to 35 years. Their QoL data were compared with those of a Dutch healthy
      reference group. Among the RB hereditary/non-hereditary survivors, the QoL was
      compared and predictors for QoL were identified by linear multiple regression
      analyses. RESULTS: As a group, RB survivors scored significantly lower than the
      reference group on the SF-36 subscale 'mental health' (t = -27, df = 86, p <
      0.01). Hereditary RB survivors scored lower on the subscale 'general health' (t =
      2.6, df = 85, p < 0.01) than non-hereditary RB survivors. Having experienced
      bullying, as a child was a predictor for the SF-36 subscales: 'physical
      functioning' (p < 0.05), 'role functioning physical' (p < 0.01), 'role
      functioning emotional' (p < 0.05) and 'social functioning' (p < 0.01). Having
      experienced bullying (p < 0.01), but also subjective experience of impairment
      related to RB (p < 0.05), was predictors for 'general health'. Subjective
      experience of impairment was a predictor for 'vitality' (p < 0.01) and 'bodily
      pain' (p < 0.01). CONCLUSION: In this exploratory study, it appears that the
      group of adult RB survivors experience a relatively good overall but slightly
      decreased QoL compared with the reference group. However, they report more
      problems with regard to their mental health (anxiety, feelings of depression, and
      loss of control). Hereditary RB survivors differ significantly from non
      hereditary RB survivors only in 'general health'. Bullying in childhood and
      subjective experience of impairment are the main predictors of a worse QoL. In
      order to prevent worsening of QoL, or perhaps to improve it, clinicians should
      make an inventory of these issues at an early stage. We recommend further
      research to assess the specific psychological factors that may lead to mental
      health problems in this population.

PMID- 17547768
TI  - Resolving RAD51C function in late stages of homologous recombination.
AB  - DNA double strand breaks are efficiently repaired by homologous recombination.
      One of the last steps of this process is resolution of Holliday junctions that
      are formed at the sites of genetic exchange between homologous DNA. Although
      various resolvases with Holliday junctions processing activity have been
      identified in bacteriophages, bacteria and archaebacteria, eukaryotic resolvases
      have been elusive. Recent biochemical evidence has revealed that RAD51C and
      XRCC3, members of the RAD51-like protein family, are involved in Holliday
      junction resolution in mammalian cells. However, purified recombinant RAD51C and
      XRCC3 proteins have not shown any Holliday junction resolution activity. In
      addition, these proteins did not reveal the presence of a nuclease domain, which
      raises doubts about their ability to function as a resolvase. Furthermore,
      oocytes from infertile Rad51C mutant mice exhibit precocious separation of sister
      chromatids at metaphase II, a phenotype that reflects a defect in sister
      chromatid cohesion, not a lack of Holliday junction resolution. Here we discuss a
      model to explain how a Holliday junction resolution defect can lead to sister
      chromatid separation in mouse oocytes. We also describe other recent in vitro and
      in vivo evidence supporting a late role for RAD51C in homologous recombination in
      mammalian cells, which is likely to be resolution of the Holliday junction.

PMID- 17547769
TI  - Nuclear import of influenza A viral ribonucleoprotein complexes is mediated by
      two nuclear localization sequences on viral nucleoprotein.
AB  - BACKGROUND: The influenza A virus replicates in the nucleus of its host cell.
      Thus, entry of the influenza genome into the cell nucleus is necessary for
      establishing infection. The genome of the influenza A virus consists of eight
      single-stranded, negative-sense RNA molecules, individually packed with several
      copies of the viral nucleoprotein (NP) into ribonucleoprotein particles (vRNPs).
      These vRNPs are large, rod-shaped complexes containing a core of NP, around which
      the RNA is helically wrapped. The vRNPs are the entities that enter the nucleus,
      and their nuclear import must be mediated by nuclear localization sequences
      (NLSs) exposed on the vRNPs. NP contains at least two putative NLSs, one at the N
      terminus (NLS1) and one in the middle (NLS2) of the protein. These NP NLSs have
      been shown to mediate the nuclear import of recombinant NP molecules. However, it
      remains to be determined which NLS mediates the nuclear import of influenza vRNP
      complexes. RESULTS: To directly track the nuclear import of the influenza A
      genome, we developed an experimental assay based on digitonin-permeabilized cells
      and fluorescently-labeled vRNPs isolated from the influenza A virus. We used this
      assay to determine the contribution of the two proposed NLSs on NP to the nuclear
      import of influenza vRNP complexes. Peptides that mimic each of the two NLSs on
      NP were used to compete with vRNPs for their nuclear import receptors. In
      addition, antibodies against the two NP NLSs were used to block the NLSs on the
      vRNP complexes, and thereby inhibit vRNP nuclear import. Both peptide competition
      and antibody inhibition of either sequence resulted in decreased nuclear
      accumulation of vRNPs. The two sequences act independently of each other, as
      inhibition of only one of the two NLSs still resulted in significant, though
      diminished, nuclear import of vRNPs. Furthermore, when both sequences were
      blocked, vRNP nuclear import was almost completely inhibited. Antibody inhibition
      studies further showed that NLS1 on NP is the main contributor to the nuclear
      import of vRNPs. CONCLUSION: Our results demonstrate that both NLS1 and NLS2 on
      NP can mediate the nuclear uptake of influenza A vRNPs.

PMID- 17547770
TI  - Hollow viscus injury in children: Starship Hospital experience.
AB  - Starship Children's Hospital in Auckland, New Zealand, serves a population of 1.2
      million people and is a tertiary institution for pediatric trauma. This study is
      designed to review all cases of abdominal injury (blunt and penetrating) that
      resulted in injury of a hollow abdominal viscus including the stomach, duodenum,
      small intestine, large intestine and urinary bladder. The mechanism of injury;
      diagnosis and outcome were studied. This was done by retrospective chart review
      of patients admitted from January 1995 to December 2001. Thirty two injuries were
      found in 29 children. The age ranged from 7 months to 15 years with boys
      represented more commonly. Small bowel was the most frequently injured hollow
      viscus. Computerized Tomography (CT scan) is an extremely useful tool for the
      diagnosis of HVI.

PMID- 17547771
TI  - Sequential use of bronchial aspirates, biopsies and washings in the preoperative
      management of lung cancers.
AB  - BACKGROUND: The combination of cytology and biopsies improves the recognition and
      typing of small cell (SCLC) versus non small cell (NSCLC) lung cancers in the
      fiberoptic bronchoscopy assessment of centrally located tumours. METHODS: We
      studied whether bronchial aspirates performed before biopsies (BA) and washings
      performed after biopsies (BW) could increase the diagnostic yield of fiberoptic
      bronchoscopy. A series of 334 consecutive samples taken in patients with
      suspicious fiberoptic bronchoscopy findings was studied. Two hundred primary
      tumours were included in the study. The actual diagnosis was based on surgical
      tissue specimen analysis and/or imaging techniques. The typing used was that of
      the 1999 WHO/IASLC classification. RESULTS: The diagnosis of malignancy and
      tumour typing were analyzed according to the sequential (combined) or single use
      of tests. Malignancy was assessed by cytology in 144/164 (87.8%) positive biopsy
      cases and in 174/200 tumour cases (87.0%). BA before biopsies allowed 84.0% of
      cancers to be diagnosed, whereas BW after biopsies allowed 79.0% of cancers to be
      found (p = ns). However, combining biopsies with BW allowed 94.0% of cancers to
      be diagnosed, whereas 82.0% were diagnosed by biopsies alone (p < 0.001). The
      highest diagnostic yield was obtained with the combination of BA, biopsies and
      BW, with 97.0% sensitivity. Exact concordance in typing was obtained in 83.8% of
      cases. The six surgically resected cases (3.0%) with negative cytology and biopsy
      results included four squamous cell carcinomas with necrotizing or fibrous
      surface and two adenocarcinomas, pT1 stage. CONCLUSION: Fiberoptic bronchoscopy
      may reach a yield of close to 100% in the diagnosis and typing of centrally
      located, primary lung cancers by combining bronchial aspirates, biopsies and
      washings.

PMID- 17547772
TI  - Understanding network concepts in modules.
AB  - BACKGROUND: Network concepts are increasingly used in biology and genetics. For
      example, the clustering coefficient has been used to understand network
      architecture; the connectivity (also known as degree) has been used to screen for
      cancer targets; and the topological overlap matrix has been used to define
      modules and to annotate genes. Dozens of potentially useful network concepts are
      known from graph theory. RESULTS: Here we study network concepts in special types
      of networks, which we refer to as approximately factorizable networks. In these
      networks, the pairwise connection strength (adjacency) between 2 network nodes
      can be factored into node specific contributions, named node 'conformity'. The
      node conformity turns out to be highly related to the connectivity. To provide a
      formalism for relating network concepts to each other, we define three types of
      network concepts: fundamental-, conformity-based-, and approximate conformity
      based concepts. Fundamental concepts include the standard definitions of
      connectivity, density, centralization, heterogeneity, clustering coefficient, and
      topological overlap. The approximate conformity-based analogs of fundamental
      network concepts have several theoretical advantages. First, they allow one to
      derive simple relationships between seemingly disparate networks concepts. For
      example, we derive simple relationships between the clustering coefficient, the
      heterogeneity, the density, the centralization, and the topological overlap. The
      second advantage of approximate conformity-based network concepts is that they
      allow one to show that fundamental network concepts can be approximated by simple
      functions of the connectivity in module networks. CONCLUSION: Using protein
      protein interaction, gene co-expression, and simulated data, we show that a) many
      networks comprised of module nodes are approximately factorizable and b) in these
      types of networks, simple relationships exist between seemingly disparate network
      concepts. Our results are implemented in freely available R software code, which
      can be downloaded from the following webpage:
      http://www.genetics.ucla.edu/labs/horvath/ModuleConformity/ModuleNetworks.

PMID- 17547773
TI  - The role of CDK in the initiation step of DNA replication in eukaryotes.
AB  - Cyclin-dependent kinases (CDKs) regulate the progression of the cell cycle in
      eukaryotes. One of the major roles of CDK is to promote chromosomal DNA
      replication. However, how CDKs promote DNA replication has been a long-standing
      question, because all the essential CDK substrates in DNA replication have not
      been identified yet. Recently Sld2 and Sld3 were identified as essential
      substrates of CDKs in the initiation step of DNA replication in budding yeast.
      Moreover, bypass of their phosphorylations is sufficient to promote DNA
      replication. Phosphorylation of Sld2 and Sld3 by CDKs enhances the formation of
      complex(es) with a BRCT (BRCA1 C-Terminal)-containing replication protein, Dpb11.
      We further propose that multiple phosphorylation by CDKs controls this process in
      budding yeast. Even though Sld3 orthologues in multicellular eukaryotes have not
      been identified, similar complex formation and, therefore, a similar mechanism of
      initiation control might be employed in eukaryotes.

PMID- 17547774
TI  - Susceptibility to obesity and gallbladder stasis produced by a protein- and fat
      enriched diet in male mice compared with female mice.
AB  - BACKGROUND: The frequency of Japanese subjects over 20 years old with metabolic
      syndrome is 45.6% in men but just 16.7% in women. The reason why Japanese male
      subjects are more susceptible to metabolic syndrome than women is unknown. One
      possibility is the higher frequency of Japanese male subjects (40-70 years old)
      who had a drinking habit (67%), while that of female subjects was only 25%. In
      addition, daily fat intake was markedly increased in Japanese subjects (from 9%
      to 25%), and cholesterol cholelithiasis is one of the most rapidly increasing
      digestive diseases during the past 50 years. The object of this study is to
      examine whether a potential sex-related risk factor exists in the manifestation
      of metabolic syndrome as well as gallstone formation. METHODS: Gallbladder
      dysmotility accerelates gallstone formation and gallbladder contraction depends
      on cholecystokinin (CCK) and its receptor (CCK-1R). We developed CCK-1R gene
      knockout (-/-) mice. The effects of the fat- and protein- enriched diet OA-2 on
      body weight, hyperlipidemia, and frequencies of sludge and gallstone formation
      were examined, and compared between wild-type and CCK-1R(-/-) male and female
      mice. The OA-2 diet contains slightly higher protein and fat (7.9 % fat and 27.6
      % protein) compared with a standard diet (CRF-1) (5.6 % fat and 22.6 % protein),
      but their total energies are similar. After weaning, CRF-1 was provided until 3
      months of age in all animals. Administration of an OA-2 diet was started when age
      matched CCK-1R(-/-) and wild-type male and female mice reached maturity, at 3
      months of age. Administration of CRF-1 was continued in the rest of the animals.
      Mice were sacrificed by guillotine at 6 and 12 months of age and the blood was
      collected to measure plasma levels of triglyceride and cholesterol. The
      gallbladder was removed and classified as normal (clear gallbladder), clouded
      (sludge formation), and/or containing gallstone formations. RESULTS: As long as
      CRF-1 was provided, the frequency of sludge and/or gallstone formation in CCK-1R(
      /-) male mice was 3 of 8 (35%) and 4 of 9 (45%) in females at 12 months of age,
      whereas no gallstone formation was observed at 6 months of age. On the other
      hand, male mice fed OA-2 increased their body weight and plasma lipid
      concentrations, compared with those fed CRF-1 regardless of genotype. Under the
      OA-2 diet, sludge and gallstone formation was observed at 6 months of age, not
      only in CCK-1R(-/-) male mice but also in wild-type male mice. In contrast,
      parameters in female mice did not differ between the two diets. CONCLUSION: Male
      mice were more susceptible to protein- and fat-enriched diet-induced obesity than
      female mice, and hyper-nutritional status accelerated sludge and gallstone
      formation in male mice.

PMID- 17547775
TI  - O6-methylguanine-DNA methyltransferase is downregulated in transformed astrocyte
      cells: implications for anti-glioma therapies.
AB  - BACKGROUND: A novel alkylating agent, temozolomide, has proven efficacious in the
      treatment of malignant gliomas. However, expression of O6-methylguanine-DNA
      methyltransferase (MGMT) renders glioma cells resistant to the treatment,
      indicating that identification of mechanisms underlying the gene regulation of
      MGMT is highly required. Although glioma-derived cell lines have been widely
      employed to understand such mechanisms, those models harbor numerous unidentified
      genetic lesions specific for individual cell lines, which complicates the study
      of specific molecules and pathways. RESULTS: We established glioma models by
      transforming normal human astrocyte cells via retroviral-mediated gene transfer
      of defined genetic elements and found that MGMT was downregulated in the
      transformed cells. Interestingly, inhibitors of DNA methylation and histone
      deacetylation failed to increase MGMT protein levels in the transformed astrocyte
      cells as well as cultured glioblastoma cell lines, whereas the treatment
      partially restored mRNA levels. These observations suggest that downregulation of
      MGMT may depend largely on cellular factors other than promoter-hypermethylation
      of MGMT genes, which is being used in the clinic to nominate patients for
      temozolomide treatment. Furthermore, we discovered that Valproic acid, one of
      histone deacetylase inhibitors, suppressed growth of the transformed astrocyte
      cells without increasing MGMT protein, suggesting that such epigenetic compounds
      may be used to some types of gliomas in combination with alkylating agents.
      CONCLUSION: Normal human astrocyte cells allow us to generate experimental models
      of human gliomas by direct manipulation with defined genetic elements, in
      contrast to tumor-derived cell lines which harbor numerous unknown genetic
      abnormalities. Thus, we propose that the study using the transformed astrocyte
      cells would be useful for identifying the mechanisms underlying MGMT regulation
      in tumor and for the development of rational drug combination in glioma
      therapies.

PMID- 17547776
TI  - Does health intervention improve socioeconomic inequalities of neonatal, infant
      and child mortality? Evidence from Matlab, Bangladesh.
AB  - BACKGROUND: Although there are wide variations in mortality between developed and
      developing countries, socioeconomic inequalities in health exist in both the
      societies. The study examined socioeconomic inequalities of neonatal, infant and
      child mortality using data from the Matlab Health and Demographic Surveillance
      System of the International Centre for Diarrhoeal Disease Research, Bangladesh
      (ICDDR,B). METHODS: Four birth cohorts (1983-85, 1988-90, 1993-95, 1998-00) were
      followed for five years for death and out-migration in two adjacent areas
      (ICDDR,B-service and government-service) with similar socioeconomic but differ
      health services. Based on asset quintiles, inequality was measured through both
      poor-rich ratio and concentration index. RESULTS: The study found that the
      socioeconomic inequalities of neonatal, infant and under-five mortality increased
      over time in both the ICDDR,B-service and government-service areas but it
      declined substantially for 1-4 years in the ICDDR,B- service area. CONCLUSION:
      The study concluded that usual health intervention programs (non-targeted) do not
      reduce poor-rich gap, rather the gap increases initially but might decrease in
      long run if the program is very intensive.

PMID- 17547777
TI  - Influence of different treatment techniques on radiation dose to the LAD coronary
      artery.
AB  - BACKGROUND: The purpose of this proof-of-principle study was to test the ability
      of an intensity-modulated radiotherapy (IMRT) technique to reduce the radiation
      dose to the heart plus the left ventricle and a coronary artery. Radiation
      induced heart disease might be a serious complication in long-term cancer
      survivors. METHODS: Planning CT scans from 6 female patients were available. They
      were part of a previous study of mediastinal IMRT for target volumes used in
      lymphoma treatment that included 8 patients and represent all cases where the
      left anterior descending coronary artery (LAD) could be contoured. We compared 6
      MV AP/PA opposed fields to a 3D conformal 4-field technique and an optimised 7
      field step-and-shoot IMRT technique and evaluated DVH's for several structures.
      The planning system was BrainSCAN 5.21 (BrainLAB, Heimstetten, Germany). RESULTS:
      IMRT maintained target volume coverage but resulted in better dose reduction to
      the heart, left ventricle and LAD than the other techniques. Selective dose
      reduction could be accomplished, although not to the degree initially attempted.
      The median LAD dose was approximately 50% lower with IMRT. In 5 out of 6
      patients, IMRT was the best technique with regard to heart sparing. CONCLUSION:
      IMRT techniques are able to reduce the radiation dose to the heart. In addition
      to dose reduction to whole heart, individualised dose distributions can be
      created, which spare, e.g., one ventricle plus one of the coronary arteries.
      Certain patients with well-defined vessel pathology might profit from an approach
      of general heart sparing with further selective dose reduction, accounting for
      the individual aspects of pre-existing damage.

PMID- 17547778
TI  - How do nurses and teachers perform breast self-examination: are they reliable
      sources of information?
AB  - BACKGROUND: Breast cancer is the most common cause of cancer-related deaths among
      women worldwide. The aim of the present study was to determine and compare
      knowledge, behavior and attitudes among female nurses and teachers concerning
      breast self-examination (BSE). METHODS: Two-hundred and eighty nine women working
      in Aydin, Turkey (125 nurses and 164 teachers) were included in the study. The
      data were collected using a questionnaire designed to measure the knowledge,
      attitudes and behavior of the groups. Analysis involved percentiles, chi2 tests,
      t tests and factor analysis. RESULTS: The knowledge of nurses about BSE was
      higher than that of teachers (81.5% versus 45.1%; p < 0.001). BSE practice
      parameters (i.e. age groups, indications, frequency) were similar (p > 0.05),
      whereas skills in performing self-examination were higher in nurses (p < 0.001).
      Fear of having breast cancer is the most frequent reason for performing BSE.
      Among nurses, the reasons for failure to perform BSE were the absence of
      prominent breast problems (82%) and forgetting (56.4%). The teachers who did not
      perform BSE said that the reasons were lack of knowledge on how to perform self
      examination (68.9%) and absence of problems (54%). Both groups had unacceptable
      technical errors in the performance of BSE. CONCLUSION: We conclude that nurses
      and teachers should be supported with information enabling them to accomplish
      their roles in the community. To improve BSE practice, it is crucial to
      coordinate continuous and planned education.

PMID- 17547779
TI  - Pitfalls in Portacath location using the landmark technique: case report.
AB  - A 34 year old woman diagnosed with breast cancer and liver metastases underwent a
      left subclavian Portacath insertion. During the procedure, the clinical features
      and the findings of intra-operative investigations provided conflicting evidence
      of the catheter position. This report highlights the potential difficulties in
      establishing long-term central venous access, the limitations of common
      investigations and safety issues relating to the process of subclavian line
      insertion.

PMID- 17547780
TI  - Pilot study of fluvoxamine treatment for climacteric symptoms in Japanese women.
AB  - BACKGROUND: Selective serotonin-reuptake inhibitors (SSRIs) are commonly
      prescribed for the treatment of depression and can be used as nonhormonal
      alternatives to manage hot flashes for women with a history of breast cancer and
      unable to take hormone replacement therapy. There are, however, few reports on
      the efficacy of SSRIs for the treatment of natural postmenopausal climacteric
      symptoms. In this pilot study, we evaluate the SSRI, fluvoxamine, for controlling
      climacteric symptoms and vasomotor symptoms, in particular. METHODS: Twenty-two
      patients were enrolled from our hospital. All were orally administered
      fluvoxamine (50 mg daily). Climacteric and depressive symptoms were assessed
      using simple menopausal index (SMI) and self-rating questionnaire for depression
      (SRQ-D), respectively, at baseline, and at 2 and 6 weeks post-treatment. RESULTS:
      Six weeks following drug administration, neither the SRQ-D nor SMI scores
      significantly decreased compared to baseline. The mean levels of vasomotor
      symptoms and mental symptoms decreased significantly following fluvoxamine
      administration, while skeletal muscle symptom scores did not. CONCLUSION: We were
      able to demonstrate that fluvoxamine was effective in treating not only
      depressive moods in climacteric symptoms but also the associated vasomotor
      symptoms. There are several limitations to this preliminary study. Future
      controlled studies are needed to further evaluate the efficacy of fluvoxamine for
      climacteric disturbances.

PMID- 17547781
TI  - Traditional knowledge on zootherapeutic uses by the Saharia tribe of Rajasthan,
      India.
AB  - The present zootherapeutic study describes the traditional knowledge related to
      the use of different animals and animal-derived products as medicines by the
      Saharia tribe reside in the Shahabad and Kishanganj Panchayat Samiti's of Baran
      district of Rajasthan, India. A field survey was conducted from April to June
      2006 by performing interview through structured questionnaire with 21 selected
      respondents, who provided information regarding use of animals and their products
      in folk medicine. A total of 15 animal species were recorded and they are used
      for different ethnomedical purposes, including cough, asthma, tuberculosis,
      paralysis, earache, herpes, weakness, muscular pain etc. The zootherapeutic
      knowledge was mostly based on domestic animals, but some protected species like
      the peacock (Pavo cristatus,), hard shelled turtle (Kachuga tentoria), sambhar
      (Cervus unicolor) were also mentioned as medicinal resources. We would suggest
      that this kind of neglected traditional knowledge should be included into the
      strategies of conservation and management of faunistic resources. Further studies
      are required for experimental validation to confirm the presence of bioactive
      compounds in these traditional remedies and also to emphasize more sustainable
      use of these resources.

PMID- 17547782
TI  - Effect of chronic stress and L-carnitine on rat stomach.
AB  - BACKGROUND AND AIM: L-Carnitine is an essential cofactor in the mitochondrial
      transfer of fatty acids, and it is also a scavenger of free radicals in mammalian
      tissues. The aim of the study was to determine the effect of L-carnitine on
      chronic restraint stress-induced gastric mucosal injury. METHODS: Wistar rats
      were applied restraint stress (1 h/day) and L-carnitine (50 mg/kg) for 21 days.
      The lesion index, prostaglandin E(2) and mucus content, lipid peroxidation,
      superoxide dismutase, and catalase activity in gastric mucosa were evaluated.
      RESULTS: Chronic restraint stress increased the lesion index, lipid peroxidation,
      and superoxide dismutase activity in gastric mucosa, and it decreased
      prostaglandin E(2) and mucus content. L-Carnitine treatment prevented the stress
      induced increase in lesion index, lipid peroxidation and a stress-induced decline
      in prostaglandin E(2), and mucus content in gastric mucosa, but it increased
      catalase activity. CONCLUSIONS: L-Carnitine prevents the occurrence of lesion by
      strengthening the gastric mucosal barrier and by reducing lipid peroxidation
      against the harmful effects of chronic restraint stress.

PMID- 17547783
TI  - [Lymphology in the training and practice of general surgeons].

PMID- 17547784
TI  - [The surgical treatment of the diastasis recti abdominis: an original technique
      of prosthesis repair of the abdominal wall].
AB  - The Authors talk about on the surgical correction of the diastasis recti
      abdominis and underline its indications and aims. Firstly, they specify the
      possibilities and define the limits of the traditional surgical method. Secondly,
      they illustrate the rational of an innovating and original technique of
      prosthesis repair of the abdominal anterior wall setted up to treat the important
      diastasis recti abdominis. Particularly, this technique is the result of a kind
      of eclecticism and integration of some phases of the Quenu's self-plastic surgery
      and of the Welti-Eudel and Chevrel's technique. Thirdly, the authors describe the
      sequence of the times of the new technique and present the preliminary clinical
      experience carried out with it. Therefore, they determine gratifying and
      encouraging the findings of this method as regards the immediate and enduring
      curative efficacy (cosmetic and functional), the security and the compliance of
      the patient. Finally, in accordance with the outcomes, the authors decide to
      defend the undoubted reliability of the prosthesis repair of the abdominal wall
      to treat the big diastasis recti abdominis. Moreover, they intend to pass
      definitive judgement on the method after further clinical experiences on larger
      series of cases.

PMID- 17547785
TI  - Adrenal pheochromocytoma and jejunal neurofibroma in type 1 neurofibromatosis:
      report of a case.
AB  - INTRODUCTION: Neurofibromatosis type 1 (NF1), known as von Recklinghausen's
      disease, is characterized by presence of cafe au lait spots, and neurofibromas in
      the skin or along the course of peripheral nerves. Diagnosis, despite extreme
      clinical variability, is defined by established diagnostic criteria. Clinical
      status is frequently complicated by systemic disorders and neoplasias. CASE
      REPORT: A case of a patient affected by NF1, with hypertension due to adrenal
      pheochromocytoma and with jejunal neurofibroma, is reported. DISCUSSION AND
      CONCLUSIONS: Variability in clinical presentation of NF1 with possible
      manifestation of severe systemic benign and malignant diseases requires strict
      follow-up and specific screening of extra-cutaneous lesions.

PMID- 17547786
TI  - [Low rectal cancer treatment in frail elderly patients. A personal series].
AB  - Rectal cancer predominantly affects elderly people, who are however more likely
      to have concomitant medical diseases and, therefore, are at higer surgical risk.
      After a careful selection of the patients, some surgical procedures can be
      performed safely. We studied a series of 149 patients affected by low rectal
      cancer; of these, 46 were aged 75 or older and comprise the elderly group; 94
      curative resections, 19 palliative surgical treatments, 31 local excisions were
      performed. This approach demonstrated to be safe and effective among older
      patients too; therefore we may conclude that it is associated with a good control
      of surgical risk and of cancer in selected patients.

PMID- 17547787
TI  - [Multiple repetitive mammary fibroadenomas. Case report].
AB  - Multiple and ripetitive mammary fibroadenomas represent a rare disease. The
      etiology is uncertain. The diagnostic radiology is able to allow a correct
      diagnosis. The authors report a case of a woman 22 years old undergone a surgical
      treatment many times to remove multiple and ripetitive mammary fibroadenomas. The
      proposed management provides for periodic radiological exams; the surgical
      treatment is proposed only for the lesions with a rapid growth.

PMID- 17547788
TI  - The misdiagnosis of ruptured abdominal aortic aneurysm: an ancient problem always
      present. Report of an atypical case.
AB  - The rupture of an abdominal aortic aneurysm is one of the most dramatic event in
      the daily clinical practice. It is often easily suspected when the classical
      signs of hemorrhagic shock are associated with an anterior (mesogastric)
      abdominal pain and an expanding mass, especially in the non-obese patients.
      Sometimes many of these signs can lack and, as a consequence, the diagnosis might
      be very difficult. This may cause a fatal delay for the patients. We describe a
      singular case in which the rupture of an abdominal aortic aneurysm was simulating
      an acute cholecystitis: the presented symptoms, together with a negative personal
      medical history, were so atypical that even four experienced practitioners
      misdiagnosed the vascular lesion and the diagnosis was possible only at autopsy.

PMID- 17547789
TI  - [Closed trauma of the spleen. Indications to surgical treatment].
AB  - The Authors mention the historical evolution that led to consider the splenectomy
      as the ideal operation in patients with post-traumatic lesions of the spleen.
      They linger then on the actual knowledges about the physiopathology of this organ
      that determined a substantial change of mind to a conservative treatment, when
      possible. By reporting their experience of the last decade, they weigh up how
      every therapeutic choice must be consequent to an accurate clinical evaluation
      that suggests the surgical abdomen exploration in urgency or, on the contrary,
      the monitoring of the patient. They linger particularly on the validity of the
      investigation and quantization of organ lesions and of the subsequent
      hemoperitoneum. The Authors end affirming that an accurate diagnostic evaluation
      and the subsequent therapy must take place in a specialized Trauma Center that
      ensures intensive monitoring and, if necessary, a timely operation in these
      patients.

PMID- 17547790
TI  - [Piezosurgery mandibular enostosis: case report].
AB  - The bone surgery has always used manual and rotary instruments. The biomedical
      engineering with ultrasound working principle has given a new surgery
      instruments, which allow a selective cutting action of bone tissue and the
      protection of soft tissue. Our case shows an uncommon clinical lesion surgically
      dangerous for the narrow adjoining of important anatomical structures as the
      lower alveolar artery and the lower alveolar nerve. The clinical result and
      recovery time go toward a smaller traumatic situation of this methodology of the
      cutting of bone tissue.

PMID- 17547791
TI  - [Bowel preparation before colonoscopy: personal experience and brief literature
      review].
AB  - INTRODUCTION: Colonoscopy is the most commonly used technique for inspection of
      the colonic mucosa. The safety and effectiveness of colonoscopy in identifying
      important colonic pathology is directly impacted by the operator experience and
      by the quality of the bowel preparation performed in anticipation of the
      procedure. PATIENTS AND METHODS: From December 2000 to June 2006, we performed
      8328 total colonoscopy (M:F ratio =1:1.8, mean age 54.7 years, range 16-93). All
      the patients were submitted to routinary bowel preparation with polyethylenglycol
      (PEG) the evening before the exam, with fibres diet restriction 5 days before the
      exam. RESULTS: On 8328 colonoscopy, 1243 were not actable for worst/absent
      intestinal toilette. 423 colonoscopy were completed after visceral washing with
      saline solution during the exam. On 1243 colonoscopy repeated, 852 were in
      subjects affected by diabetes (p < 0.05); in these patients we prescribed 5
      litres solution of PEG one day before the endoscopy, diet without fibers 7 days
      before the exam and the use of 250 ml solution of PEG (bid): with these method,
      all the patients were submitted successfully to colonoscopy and retrograde
      ileoscopy. DISCUSSION: Physicians favor preparations associated with the best
      patient compliance to achieve the best results. Patients favour preparations that
      are low in volume, palatable, have easy to complete regimens, and are reimbursed
      by health insurance or are inexpensive. Both patients and physicians favor
      preparations that are safe to administer in light of existing comorbid conditions
      and those that will not interact with previously prescribed medications.
      CONCLUSIONS: Today doesn't exist the "gold standard" for bowel preparation before
      colonoscopy. Basing on our experience, the 4 litres PEG solution mentioned above
      is well tolerated and effective. In patients with severe comorbidity (diabetes,
      renal failure, high blood pressure) only little modifications are required to
      optimize the colon cleansing.

PMID- 17547792
TI  - [Telemedicine].
AB  - Recent innovations in the area of telecommunications, computer science and
      technical scientific devices have contributed to the development of interesting
      future perspectives in the medical sector and in the sanitary structure
      organization. These innovations may contribute to the sensible reduction of costs
      in a struggling sanitary system. It may become possible to manage not only the
      patient from a distance but also the numerous medical, informational and
      statistical data freeing important medical and paramedical personnel resources
      from carrying out the most simple activities. The ability to monitor the main
      vital parameters of a multi-traumatised patient, or the ability to contact a
      specialist without the need to transfer the patient, would be some of the most
      simple benefits of the new medical area called telemedicine.

PMID- 17547793
TI  - [Insulin resistance as an early marker of non-alcoholic fatty liver].

PMID- 17547794
TI  - [Prevention and treatment of diabetic nephropathy].

PMID- 17547795
TI  - [Evaluation of new technologies in interventional treatment of certain heart
      diseases].

PMID- 17547796
TI  - [A survey of microalbuminuria prevalence in hypertensive type 2 diabetic patients
      in mainland China].
AB  - OBJECTIVE: To determine the prevalence and risk factors of microalbuminuria (MA)
      in diabetic patients with hypertension in mainland China. METHODS: This cross
      sectional study involved 2473 patients enrolled from 42 diabetic and cardiac
      outpatient clinics. An immunospecific dipstick Micral Test II was used for MA
      screening and Nephur7 urinary strip for macroalbuminuria. In addition, blood
      pressure levels were recorded and questionnaire forms were filled out. Chi square
      and logistic regression analyses were used for statistical analyses. RESULTS: In
      the study population the prevalence of MA in hypertensive type 2 diabetic
      patients was 42.9% and that of macroalbuminuria was 17.0%. Logistic regression
      analysis showed that age, BMI and systolic blood pressure were independently
      associated with the occurrence of MA, while the duration of type 2 diabetic and
      diuretics used were independently associated with the occurrence of
      macroalbuminuria. CONCLUSIONS: It is shown that there is a high prevalence of MA
      in hypertensive diabetic patients. Screening of MA and lowering of blood pressure
      should be the important measures for lowering its occurrence.

PMID- 17547797
TI  - [The reference values of glycemic parameters for continuous glucose monitoring
      and its clinical application].
AB  - OBJECTIVE: To establish reference values of glycemic parameters for continuous
      glucose monitoring in Chinese. METHODS: Forty-eight individuals with normal
      glucose regulation were observed with continuous glucose monitoring system (CGMS)
      for 3 days. Indexes in CGMS were analyzed, including mean level of 24 h blood
      glucose (BG) values (24 h MBG) and its standard deviation (SDBG), percentage of
      time above 7.8 mmol/L or below 3.9 mmol/L, area under the curve (AUC) of BG above
      5.6 mmol/L, the largest amplitude of glycemic excursions (LAGE), mean amplitude
      of glycemic excursions (MAGE) and absolute means of daily differences (MODD).
      RESULTS: (1) The upper limits of indexes for continuous glucose monitoring were
      as follows: 6.5 mmol/L for 24 h MBG, 6.0 mmol/L, 6.3 mmol/L and 6.0 mmol/L for
      mean BG levels 1 h before breakfast, lunch and dinner respectively, 7.0 mmol/L,
      6.7 mmol/L and 7.0 mmol/L for mean BG levels 3 h after breakfast, lunch and
      dinner respectively, 1.4 mmol/L for SDBG, 5.7 mmol/L for LAGE, 3.4 mmol/L for
      MAGE and 1.4 mmol/L for MODD. The percentage of time over 7.8 mmol/L was less
      than 9%, while the percentage of time below 3.9 mmol/L was less than 20%. The AUC
      of BG above 5.6 mmol/L was less than 0.9 d x mmol x L(-1). There was no
      statistical difference among sex subgroups (P > 0.05). (2) The correlations of
      24h MBG with MAGE, MODD and SDBG were not significant (P > 0.05). MAGE was
      positively correlated with SDBG (r = 0.93, P < 0.01). CONCLUSION: The reference
      values of glycemic parameters for continuous glucose monitoring are initially
      established and can be used as a temporary reference for clinical practice in
      Chinese. The CGMS profile can reflect the overall BG control and the feature of
      glycemic excursions in detail.

PMID- 17547798
TI  - [The effect of enteral nutritional suspension (diabetes) (TPF-DM) on blood
      glucose, serum insulin and lipids in patients with type 2 diabetes].
AB  - OBJECTIVE: To investigate the effect of a new enteral nutrition suspension
      (diabetes) (TPF-DM) (Dixson 0.75 kcal/ml) (1 kcal = 4.184 kJ) on blood glucose,
      serum insulin and lipids as compared with a standard formula (Nutrition MF 0.75
      kcal/ml) in patients with type 2 diabetes. METHODS: A randomized, controlled,
      paralleled and single center trial was carried out. A total of 76 patients with
      type 2 diabetes without using insulin and obvious complications were randomized
      into a study group and a control group. 36 patients in the study group and 35 in
      the control group completed the trial. The observation lasted 6 days. All
      calories came from enteral nutrition. At baseline all the patients had standard
      mixed meal (bread 50 g, egg 50 g, milk 250 ml, total calorie 400 kcal) test and
      at the end of the trial a enteral nutrient meal (enteral nutrient 400 ml, total
      calorie 300 kcal) test. Blood samples were taken before the meal and 30, 60, 120
      and 180 minutes after the meal to test plasma glucose, serum insulin, serum
      lipids and some safety parameters. The area under curve (AUC) for plasma glucose,
      serum insulin, serum lipids was calculated. RESULTS: Compared with the mixed meal
      test, the AUC of plasma glucose and serum insulin during both Dixson 0.75 kcal/ml
      test and standard formula (Nutrition MF 0.75 kcal/ml) test were significantly
      lower (P < 0.01). The change at baseline in the study group was more than that in
      the control group [the change of AUC for plasma glucose (-6.42 +/- 8.62) h x mmol
      x L(-1) vs (-1.87 +/- 5.30) h x mmol x L(-1), P < 0.01; that of AUC for serum
      insulin (-36.94 +/- 49.77) h x mIU x L(-1) vs (-18.20 +/- 32.62) h x mIU x L(-1),
      P < 0.05]. Both the enteral nutrition formula can reduce insulin resistance
      (calculated by HOMA-IR), but there was no difference between them. There was no
      significant effect on total cholesterol, high density lipoprotein and low density
      lipoprotein. AUC of serum triglycerides was lower during the tests with both
      enteral nutrients than that during mixed meal test, but there was no significant
      difference between the two groups. There was no safety concern about the enteral
      nutrition. CONCLUSION: Enteral nutrition suspension (diabetes) (TPF-DM) (Dixson
      0.75 kcal/ml) is an effective and safe enteral nutrient to be used in patients
      with type 2 diabetes.

PMID- 17547799
TI  - [Analysis of the mechanisms of thrombosis after implantation of drug-eluting
      stents].
AB  - OBJECTIVE: Stent thrombosis has been regarded as a severe complication of PCI
      therapy, therefore, analyzing the causes of thrombosis after implantation of drug
      eluting stents (DES) is necessary. METHODS: This is a single center study with no
      limitation of entry criteria for using DES in patients with coronary heart
      disease (CHD). From Dec. 2001 to Dec. 2005, 3345 consecutive patients underwent
      implantation with Cypher stents (eluted with sirolimus: 2165 patients, 2362
      lesions, 2695 stents) or TAXUS stents (eluted with paclitaxel: 1180 patients,
      1453 lesions, 1725 stents) in our hospital. 10-month follow-up was completed in
      2296 patients (1455 patients with 1632 lesions using 1773 Cypher stents & 841
      patients with 1032 lesions used 1182 TAXUS stents). All patients were treated
      with aspirin plus clopidogrel at least 9 months after PCI procedure. RESULTS:
      Among 3345 patients, 9 patients had acute stent thrombosis (0.27%): 7 in the
      sirolimus group, 2 in the paclitaxel group (0.32% vs 0.17%, P = 0.637), 7
      patients had subacute stent thrombosis (0.21%): 5 in the sirolimus group and 2 in
      the paclitaxel group (0.23% vs 0.17%, P = 0.526) and 13 patients had late stent
      thrombosis (0.57%): 5 in the sirolimus group and 8 in the paclitaxel group (0.34%
      vs 0.95%, P = 0.114) Among the 29 patients with DES thrombosis. 8 patients
      (26.7%) presented as sudden death, 13 nonfatal MI and 8 unstable angina. Stent
      thrombosis was demonstrated by angiography in 21 patients (72.4%). The causes of
      acute and subacute DES thrombosis were related to suboptimal stenting in 8
      patients including 7 patients with bifurcation lesions or to uncovered injury
      segment of the diffuse lesions in five patients. The causes for late thrombosis
      were discontinuation of antiplatelet drugs in four cases and related to poor left
      ventricular function in 6 cases with history of old myocardial infarction.
      CONCLUSIONS: Our study showed that suboptimal stenting, especially for
      bifurcation lesions and uncovered injury segment of diffuse lesions were the main
      causes of acute and subacute stent thrombosis. Left ventricular disfunction and
      premature discontinuation of antiplatelet therapy were the main reasons of late
      thrombosis.

PMID- 17547800
TI  - [The application of a 0.75 mg/kg intra-arterial dose of enoxaparin in coronary
      angiography and percutaneous coronary intervention].
AB  - OBJECTIVE: This study was designed to examine the efficacy and safety of a dose
      of 0.75 mg/kg intra-arterial enoxaparin in elective percutaneous coronary
      intervention in Chinese population. METHODS: A total of 160 consecutive patients
      undergoing elective PCI were randomized to either enoxaparin or UFH (80 cases for
      each) group for procedural anticoagulation. The patients in enoxaparin group were
      given a bolus of enoxaparin (0.75 mg/kg) intra-arterially before PCI, and a
      superaddition (0.3 mg/kg) would be administered if the procedural time > 90
      minutes. Serial plasma anti-X a factor activities were measured before and after
      the bolus of enoxaparin. The patients in UFH group were given a bolus of UFH (100
      U/kg) intra-arterially before PCI and ACT was controlled between 250 and 300
      seconds. Then coronary angiography and PCI was performed immediately. Bleeding
      complications were classified according to thrombolysis in myocardial infarction
      (TIMI) criteria. All patients were monitored for thrombosis during PCI and
      adverse events (i.e. death, myocardial infarction demanding revascularization) 30
      days after PCI. RESULTS: 159 patients completed the procedure. Plasma anti-X a
      factor activities in patients of the enoxaparin group were above 0.5 IU/ml 5
      minutes to 2 hours after enoxaparin (0.75 mg/kg) injection and the measurements
      in 61% of the patients were above 0.5 IU/ml 3 hours after injection. If a
      supplement of 0.3 mg/kg of enoxaparin was given after 90 minutes, plasma anti-X a
      factor activities of all the patients were above 0.5 IU/ml within 4 hours after
      the procedure. As compared with UFH, enoxaparin increased the likelihood of
      thrombosis significantly in sheath catheter during PCI (26.6% vs 10.0%, P <
      0.001). There was no obvious difference in adverse events (2.5% vs. 2.6%, P >
      0.05) and bleeding events (2.5% vs 3.8%, P > 0.05) between the two groups.
      CONCLUSIONS: A 0.75 mg/kg intra-arterial dose of enoxaparin for anticoagulation
      in patients undergoing elective PCI is safe and effective. Anticoagulation effect
      can be maintained for at least 2 hours. An additional bolus is proposed when
      procedure time exceeds 2 hours.

PMID- 17547801
TI  - [Stent-assisted angioplasty and long-term results in atherosclerotic vertebral
      artery ostial stenosis].
AB  - OBJECTIVE: To evaluate the safety, feasibility and long-term results of stent
      assisted angioplasty in atherosclerotic ostial stenosis of vertebral artery (VA).
      METHODS: Forty one patients (48 lesions) with symptomatic cerebral ischemic
      events or stroke attributed to VA atherosclerotic ostial stenosis > or = 50%
      (NASCET method) found in digital subtraction angiography (DSA) were approached
      for consent to participate in the study. During the procedure, three cases used
      protection devices and three used drug-eluting stents. RESULTS: Thirty seven of
      the patients were male and 4 female. Mean age was 63.4 years (range 36 - 80).
      Technical success was achieved in 97.9 % of the lesions. One suffered from a
      stroke that occurred within 30-days postprocedural. 37 patients were followed up
      for 22.4 months. The clinical follow-up outcomes showed that there were no lesion
      related strokes and deaths, three appeared to have return of neurological
      symptoms (TIA). Among the 21 patients (26 lesions) who had angiography follow-up,
      re-stenosis (> or = 50%) was revealed in 9 patients (9 lesions) (34.6%). However,
      seven of these 9 patients remained asymptomatic. CONCLUSIONS: Stent-assisted
      angioplasty for atherosclerotic ostial stenosis of VA is safe and feasible. It
      can prevent the lesion-related stroke, death and TIA recurrence. However, further
      studies are needed to clarify how to reduce the relatively high re-stenosis rate.

PMID- 17547802
TI  - [A clinical analysis of 23 cases of allergic bronchopulmonary aspergillosis].
AB  - OBJECTIVE: To describe the clinical characteristics of allergic bronchopulmonary
      aspergillosis (ABPA). METHODS: The clinical presentations, serologic results,
      lung function data, chest radiology and the results of treatment of 23 patients
      with ABPA in Peking Union Medical College Hospital were retrospectively analyzed.
      RESULTS: There were 11 males and 12 females, with a mean age of (34.0 +/- 13.2)
      yrs. Tuberculosis, pneumonia, lung cancer and Wegener's granulomatosis were
      initially diagnosed in 12, 3, 2 and 1 cases respectively. Cough was present in
      all patients and sputum production in 22 cases, wheeze in 18, sputum plugs in 16,
      fever in 15 (high degree of fever in 4), hemoptysis in 12, chest pain/backache in
      8 and weight loss in 7 cases. Forced expired volume in one second (FEV(1)) was
      (54.7 +/- 24.1)% predicted, and FEV(1)/forced vital capacity (FVC) was (62.5 +/-
      11.9)%. The FEV(1) reversibility was found in 56% (9/16) of the patients. Chest
      CT were performed in 22 cases. Patchy infiltrations were present in 21, central
      bronchiectasis in 17, nodular opacities in 9, mucoid impaction (glover
      finger/band linear opacities) in 6, consolidation in 5, and mediastinal
      adenopathy in 11 cases, while 17 cases presented fleeting infiltrations. Twenty
      two patients were treated with prednisone plus itraconazole and 17 patients were
      followed. The median follow up time was 26.2 months (13 days -19 years).
      Pulmonary infiltrations relapsed in 9 patients and not appeared for more than 6
      years in only one patient. CONCLUSIONS: ABPA was mostly misdiagnosed as
      tuberculosis. Wheeze is present in almost all patients with ABPA, which can be
      useful in differentiation from tuberculosis. Obstructive ventilatory defect,
      peripheral blood eosinophilia, fleeting pulmonary infiltration and central
      bronchiectasis were features of ABPA. Measurement of total IgE, A.fumigatus
      specific IgE levels and immediate cutaneous reaction to A.fumigatus are helpful
      for confirmation of the diagnosis.

PMID- 17547803
TI  - [The oxidative DNA damage of monocytes and its in vitro repair by melatonin in
      patients with tuberculous pleurisy].
AB  - OBJECTIVE: To explore the level of mononuclear cell oxidative DNA damage and the
      total antioxidative capacity (TAC) in patients with tuberculous pleurisy. To
      evaluate the in vitro repair effects of melatonin on mononuclear cell DNA damage
      in pleural effusion of the patients. METHODS: The mononuclear cell DNA damages in
      pleural effusion and peripheral blood of 28 patients with tuberculous pleurisy
      and in peripheral blood of 25 healthy persons were detected by single cell gel
      electrophoresis (comet%). The levels of TAC in supernatant of pleural effusion
      and blood plasma of 28 patients and in blood plasma of 25 healthy persons were
      measured by o-phenanthroline colorimetric analysis. The mononuclear cells from
      pleural effusions of 20 patients were treated by melatonin in vitro. RESULTS: The
      comet percentage of mononuclear cells in pleural effusion from patients with
      tuberculous pleurisy was (41.3 +/- 14.5)%, which was higher than in peripheral
      blood (21.2 +/- 4.2)%, P < 0.01. The level of TAC in supernatant of pleural
      effusion was (5.17 +/- 1.19) U/ml, which was lower than in blood plasma (8.66 +/-
      1.59) U/ml, P < 0.01. There was a negative correlation between the comet
      percentage of mononuclear cells and the level of TAC (r = -0.425, P < 0.05) in
      pleural effusion. The comet percentage of mononuclear cells in peripheral blood
      from patients was (21.2 +/- 4.2)%, which was higher than from controls (8.9 +/-
      3.7)%, P < 0.01. The level of TAC in blood plasma was (8.66 +/- 1.59) U/ml, which
      was lower than from the controls (10.61 +/- 1.39) U/ml, P < 0.01. After treatment
      with melatonin, the comet percentage of mononuclear cells in pleural effusion
      decreased from (40.8 +/- 9.3)% to (11.0 +/- 3.7)%, P < 0.01. CONCLUSION: There
      are oxidative DNA damage and oxidation/antioxidation imbalance in patients with
      tuberculous pleurisy, particularly in the diseased pleural cavity. Melatonin can
      facilitate, probably by its antioxidative effects, the in vitro repair of the
      damaged DNA of mononuclear cells from pleural effusion of patients with
      tuberculous pleurisy.

PMID- 17547805
TI  - [An analysis of the early diagnostic criteria for tuberculosis meningitis].
AB  - OBJECTIVE: To find a method for the early diagnosis of tuberculous meningitis
      (TM). METHODS: Cases with the discharge diagnosis of TM during 1995 - 2004 ten
      years in the Peking Union Medical College Hospital were analyzed retrospectively.
      History of tuberculosis other sites of tuberculous infection, the findings of
      cerebrospinal fluid (CSF) and CSF culture result were studied. RESULTS: 16 of the
      68 patients had past history of tuberculosis. During hospitalization 20 had
      pulmonary tuberculosis, while 9 had other sites of tuberculous infection. The
      rate of tuberculous infection aside from neurological system was 43%. The top 7
      clinical manifestations were: coma, onset of the disease more than 5 days,
      lymphocyte predominant in CSF, glucose level in CSF 50% lower than that of blood,
      abnormal CT findings. Abnormal ocular fundi and proved tuberculosis of other
      sites. CONCLUSIONS: TM is often accompanied with tuberculous infection of other
      sites. Its diagnosis can not be relied mainly on the culture result of CSf. When
      4 of the 7 above mentioned criteria are present, TM should be diagnosed and anti
      tuberculosis therapy started.

PMID- 17547806
TI  - [Anti-Helicobacter pylori effect and regulation of T helper response of
      chitosan].
AB  - OBJECTIVE: To study the anti-Helicobacter pylori (Hp) effect and the regulation
      of T helper (Th) response of chitosan. METHODS: Hp infected grade one female
      BALB/c mice model was established by inoculating Hp Sydney strain 1 and the mice
      were randomly divided into eight groups and administrated with (1) Arabia glue
      solution (control group), (2) omeprazole, (3) amoxicillin, (4) amoxicillin plus
      omeprazole, (5) chitosan, (6) chitosan plus omeprazole, (7) chitosan plus
      amoxicillin, (8) chitosan plus amoxicillin plus omeprazole respectively twice
      daily for 14 consecutive days. Four weeks after the last administration, these
      mice were all killed and samples of gastric mucosa were embedded in paraffin,
      sectioned and assayed with Giemsa stain. The remaining gastric mucosa was used to
      quantitatively culture Hp. An quantitative ELISA was used to detect IL-2,
      IFNgamma, IL-12, IL-4, IL-10 content in gastric mucosa. RESULTS: The eradication
      rate of Hp was 0, 0, 41.7%, 58.3%, 58.3%, 66.7%, 83.3% and 91.7% respectively
      among these eight groups (P < 0.01). The Hp colony density in the (1) group and
      (2) group was significantly higher than that in the other six groups (P < 0.05).
      The Hp colony density in (3) group was significantly higher than that in (6)
      group, (7) group and (8) group (P < 0.05) and that in (4) group was significantly
      higher than that in (8) group (P < 0.05). There was no difference in the content
      of IL-2 in the gastric mucosa among these eight groups (P > 0.05). The content of
      IFNgamma, IL-12, IL-4 and IL-10 in the gastric mucosa in groups with chitosan was
      significantly higher than that in groups without chitosan (P < 0.05).
      CONCLUSIONS: Chitosan has anti-Hp effect and synergism with amoxicillin in vivo.
      Chitosan can up-regulate Th1 and Th2 response.

PMID- 17547807
TI  - [Real-time reverse-transcriptase polymerase chain reaction in monitoring BCR/ABL
      transcript levels in chronic myeloid leukemia patients after allogeneic
      hematopoietic stem cells transplantation].
AB  - OBJECTIVE: To monitor the gene expression of BCR/ABL in chronic myeloid leukemia
      patients after allogeneic hematopoietic stem cells transplantation with real-time
      RT-PCR for evaluating therapeutic efficacy and guiding further treatment.
      METHODS: Taqman real-time RT-PCR technique was performed to monitor peripheral
      blood BCR/ABL transcript levels in 10 patients at the time of diagnosis and
      serially at intervals in 25 patients after allogeneic hematopoietic stem cells
      transplantation. beta-actin mRNA was used as an endogenous reference. RESULTS:
      The sensitivity of real-time RT-PCR was 10 copies/microl. In 15 patients
      receiving transplantation, the median of N(BCR/ABL) (%) before transplantation, 1
      month after transplantation and 2 months after transplantation was respectively:
      6.57 (0.14 - 38.83), 0.10 (0 - 1.71) and 0 (0 - 0.52). 3 months later N(BCR/ABL)
      (%) all turned to 0. BCR/ABL transcripts after transplantation were detected to
      decrease gradually. N(BCR/ABL) (%) 1 month after transplantation and 2 months
      after transplantation was both lower than that before transplantation (chi(2)
      both = 13.07, P < 0.01). N(BCR/ABL) (%) at 2 months after transplantation was
      lower than that at 1 month after transplantation (chi(2) = 8.10, P < 0.01). In 10
      other patients, N(BCR/ABL) (%) was 0 in consecutive tests from 3 to 43 months
      after transplantation. CONCLUSION: Real-time RT-PCR is sensitive, reliable and
      reproducible for monitoring CML relapse after transplantation. It is of help in
      detecting minimal residual disease, predicting the prognosis of the disease and
      providing practical indications for further treatment.

PMID- 17547808
TI  - [A study of the clinical classification of 3638 cases of mushroom poisoning].
AB  - OBJECTIVE: To study the clinical classification and characteristics as well as
      prognosis of mushroom poisoning. METHODS: We retrospectively analyzed 191 papers
      published domestically for 3466 cases of mushroom poisoning from 1995 to 2004 and
      studied the Xinqiao Hospital data of 172 cases of mushroom poisoning treated from
      1980 through 2004. We made a retrospective investigation and clinical
      classification of all the 3638 cases of mushroom poisoning. RESULTS: Among the
      3638 patients, clinical manifestations as gastroenteritis were found in 571, all
      of them were cured. The most common symptoms were those of acute renal failure
      being found in 1450 cases; 1414 were cases (97.5%) and 36 died (2.5%). Symptoms
      of toxic hepatitis were found in 1010 cases, 841 were cases (83.3%) and 169 died
      (16.7%). Psychoneurological disorder was manifested in 214 cases; 197 were cases
      (92.1%) and 17 died (7.9%). Erythrolysis was found in 73 cases; 71 were cases
      (97.3%) and 2 died (2.7%). The therapeutic effect and prognosis of mushroom
      poisoning with different clinical manifestation varied very significantly (P <
      0.001). Of the 320 cases clinically unclassified, multiple organ dysfunction
      syndrome was found in 222 cases; 98 were cases (44.1%) and 124 died (55.9%).
      Definite classification could not be made in 98 cases; 90 were cases (91.8%) and
      8 died (8.2%). CONCLUSIONS: The clinical classification of mushroom poisoning was
      usually of four types as described in the textbooks or special articles, but it
      should be of five types according to the analysis of the data of the present
      study, i.e. gastroenteritis type, acute renal failure type, toxic hepatitis type,
      psychoneurological disorder type and erythrolysis type. It is not clear whether
      there is a mixed type or not. Further investigation is needed in this respect.

PMID- 17547825
TI  - Should antiretroviral therapy be started earlier?
AB  - Current treatment guidelines recommend that antiretroviral therapy be deferred
      until the CD4 count has fallen into the 200 to 350 cells/mm(3) range. However,
      treatment has become simpler, less toxic, and more forgiving of missed doses.
      Longer-term follow-up data from clinical cohorts are now showing better outcomes
      when therapy is started at higher CD4 cell counts. Therapy initiated early has
      better virologic and immunologic responses, is better tolerated, and is cost
      effective. Recent developments and clinical data support a return to earlier
      initiation of therapy.

PMID- 17547826
TI  - Confronting proviral HIV infection.
AB  - The course of HIV infection is arrested by antiretroviral therapy (ART). However,
      life-long ART is undesirable. To eradicate infection, strategies are needed to
      deplete the rare population of proviral genomes that persist and reemerge if ART
      is interrupted. Proviral HIV persists due to the simultaneous deficiency of
      factors required to allow proviral expression and virion production, and a
      predominance of factors that obstruct proviral expression. Combining ART with
      global inducers of T-cell activation has so far failed to eradicate HIV
      infection. One approach to the selective removal of obstacles to proviral
      expression, inhibition of the chromatin remodeling enzyme histone deacetylase,
      has entered clinical testing. Additional approaches may be needed. Ultimately,
      therapies that eliminate rare cells that persistently express HIV and interrupt
      low levels of viremia that persist in some patients may be required to render
      depletion of proviral HIV infection clinically relevant, and lead to the
      clearance of HIV infection.

PMID- 17547827
TI  - Adherence-resistance relationships to combination HIV antiretroviral therapy.
AB  - Early views on the relationship between adherence and resistance postulated a
      bell-shaped relationship that balanced selective drug pressure and improved viral
      suppression along a continuum of adherence. Although this conceptual relationship
      remains valid, recent data suggest that each regimen class may have different
      adherence-resistance relationships. These regimen-specific relationships are a
      function of the capacities of resistant virus to replicate at different levels of
      drug exposure, which are largely, but not entirely, determined by the impact of
      mutations on susceptibility of the virus and the impact of the mutations on the
      inherent ability of the virus to replicate efficiently. Specific patterns of
      adherence, such as treatment discontinuations, may influence adherence-resistance
      relationship to combination regimens comprised of medications with differing half
      lives. Host genomics that alters antiretroviral drug distribution and metabolism
      may also impact adherence-resistance relationships. Optimal antiretroviral
      regimens should be constructed such that there is little overlap in the window of
      adherence that selects for antiretroviral drug resistance.

PMID- 17547828
TI  - Antiretroviral treatment strategies in resource-limited settings.
AB  - To date, a minority of persons living with HIV worldwide has benefited from the
      advances in HIV therapeutics fueled by the scientific community, policy-makers,
      advocates, and the pharmaceutical industry in the global North. A growing body of
      evidence demonstrates that access to highly active antiretroviral therapy can be
      successfully scaled-up in less wealthy nations in the South. High rates of
      adherence correspond with clinical, immunologic, and virologic outcomes similar
      to those seen in wealthier nations. Recent reports of successful programs
      highlight the provision of free care, reliance on the international funding
      sources, and proactive adherence counseling. As access to antiretroviral therapy
      has improved, there is an urgent need to develop better strategies for initiating
      and monitoring therapy, including the scale-up of viral load testing.

PMID- 17547829
TI  - Does antiretroviral therapy prevent HIV transmission to sexual partners?
AB  - The majority of HIV-1 infections are acquired sexually, and interventions to
      prevent sexual transmission are urgently needed to curb the growth of the HIV
      pandemic. The potential role of antiretroviral therapy in preventing sexual
      transmission of HIV is still emerging. Highly active antiretroviral therapy has
      been shown to decrease HIV RNA shedding in the genital tract, and its use among
      serodiscordant couples has been associated with reduced seroconversions in
      partners who are HIV negative. However, other studies have associated the use of
      antiretroviral therapy with increased HIV transmission risk behaviors. In this
      review, we explore the rationale for using highly active antiretroviral therapy
      to prevent sexual transmission of HIV including its role in prevention strategies
      at the population level, as well as the cost-effectiveness and potential
      limitations of this approach.

PMID- 17547830
TI  - Interventions for body habitus changes associated with HIV infection and its
      treatment.
AB  - Lipodystrophy and its two components lipo-accumulation and lipoatropy are very
      common among individuals with HIV infection on treatment, especially among those
      who started therapy in the late 1990s and early 2000s. This review discusses the
      current management of these complications of HIV and its treatment. For the
      purpose of clarity in this review, we have divided the interventions according to
      the predominant phenotype of the individual.

PMID- 17547831
TI  - Treatment of children with HIV infection.
AB  - The treatment of pediatric HIV infection has seen vast improvements in terms of
      better long-term suppression of HIV replication and subsequent improvements in
      the longevity and quality of life in children. This has been realized, in part,
      by development of newer antiretroviral medications, better knowledge about the
      pharmaco-kinetics of these drugs in children, and improved insight on drug
      toxicities in children. This review will discuss some of the newer agents that
      may be available for children in the near future, in addition to new
      pharmacokinetic and toxicity data that are specific to the pediatric patient. New
      information on key vaccines that should be administered to children with HIV
      infection is also discussed.

PMID- 17547833
TI  - ADOPT: lessons from comparison of glycemic durability of rosiglitazone,
      metformin, or glyburide monotherapy.

PMID- 17547832
TI  - The new diabetes inhalers: new tools for the clinician.

PMID- 17547834
TI  - NASH and the risk of cirrhosis and hepatocellular carcinoma in type 2 diabetes.
AB  - The risk of chronic liver disease and liver-related mortality is increased in
      patients with type 2 diabetes mellitus. Several cohort studies have suggested a
      metabolic pathway from nonalcoholic fatty liver, nonalcoholic steatohepatitis,
      cryptogenic cirrhosis, and eventually hepatocellular carcinoma. Although
      cardiovascular risk remains the major cause for excess mortality in type 2
      diabetes mellitus, the risk of progressive liver disease should no longer be
      underscored.

PMID- 17547835
TI  - Nonalcoholic fatty liver disease and cardiovascular disease risk.
AB  - Nonalcoholic fatty liver disease (NAFLD) is prevalent in people with the
      metabolic syndrome and type 2 diabetes. Evidence is now accumulating that NAFLD
      is associated with obesity and diabetes and may serve as a predictor of
      cardiovascular disease. Although at present, treatment of the individual risk
      factors pertinent to NAFLD is advocated, novel therapies are emerging that may
      target steatosis and/or inflammation, thus ameliorating the overall
      cardiovascular disease risk. Long-term outcome studies need to establish whether
      treatment of NAFLD (and in particular which therapy) will affect the long-term
      outcome.

PMID- 17547836
TI  - Antihypertensive agents, insulin sensitivity, and new-onset diabetes.
AB  - The effects of the antihypertensive drugs on carbohydrate metabolism and the
      development of diabetes have been a major research field for more than two
      decades. Many clinical studies have investigated the effects of the
      antihypertensive classes on insulin sensitivity and glycemic control, whereas
      several observational studies and large outcome trials have examined associations
      of antihypertensive agents with diabetes incidence. In general, thiazide
      diuretics and conventional beta blockers decrease insulin sensitivity and
      increase new-onset diabetes, whereas angiotensin-converting enzyme inhibitors,
      calcium channel blockers, and angiotensin II receptor blockers have neutral or
      beneficial effects on these parameters. However, several issues in this field,
      such as the specific properties of newer agents and the relationship of adverse
      metabolic outcomes and cardiovascular risk, remain to be fully elucidated. This
      article presents and evaluates the current knowledge in this important area.

PMID- 17547837
TI  - Prevention of type 2 diabetes: an update.
AB  - With the rising tide of the diabetes epidemic leading to increased morbidity and
      mortality (primarily from cardiovascular disease), together with failure to
      control the disease and its associated complications, prevention of diabetes
      appears to be the logical option for curbing this epidemic. Several trials have
      been completed, and others ongoing, using various strategies for diabetes
      prevention. In this review, we provide an update on diabetes prevention
      strategies, highlighting the rationale behind such interventions, together with
      an outlook of the ongoing efforts that are likely to provide additional options
      for patients at risk for diabetes.

PMID- 17547838
TI  - Hypertension in people with diabetes and the metabolic syndrome: pathophysiologic
      insights and therapeutic update.
AB  - Hypertension (HTN) and type 2 diabetes mellitus (T2DM) are emerging as epidemics
      of the 21st century and are important components of the metabolic syndrome (MS).
      Evidence demonstrates a relationship between HTN, T2DM, and several vascular and
      metabolic abnormalities that are components of the MS. HTN affects nearly 70
      million Americans and over one billion worldwide; likewise, the MS affects 44% of
      the US population above the age of 60 years and is rapidly increasing. HTN
      associated with the MS has certain pathophysiologic characteristics that provide
      clinical challenges. There is growing evidence that tissue activation of the
      renin-angiotensin system contributes to endothelial dysfunction,
      microalbuminuria, insulin resistance, and subsequent increased risk for
      cardiovascular and chronic kidney disease. The notion that HTN is a metabolic as
      well as a vascular disease provides a new treatment paradigm.

PMID- 17547839
TI  - Effects of hyperglycemia and hyperinsulinemia on the tissue factor pathway of
      blood coagulation.
AB  - Tissue factor (TF) is the primary initiator of blood coagulation. Circulating TF
      procoagulant activity (TF-PCA) is associated with blood cells and microparticles
      and is elevated in patients with type 2 diabetes mellitus. Combined
      hyperinsulinemia and hyperglycemia and to a lesser degree selective
      hyperinsulinemia for 24 hours in healthy volunteers increased circulating TF-PCA,
      monocyte TF surface expression and mRNA, plasma thrombin generation, and
      coagulation factors VII and VIII activities, suggesting that the coagulation
      system had been activated. In addition, platelet CD40L and platelet-monocyte
      aggregates increased, indicating platelet activation. Somatostatin abolished
      these changes. We conclude that hyperinsulinemia, but particularly the
      combination of hyperinsulinemia and hyperglycemia, creates a prothrombotic state
      and may, in addition, be proinflammatory and proatherogenic by virtue of the
      actions of CD40L and TF.

PMID- 17547840
TI  - Dyslipidemia in type 2 diabetes mellitus.
AB  - Cardiovascular disease is a significant cause of morbidity and mortality in
      patients with diabetes mellitus (DM). DM is now recognized as a risk equivalent
      for coronary heart disease. The lipid profile in patients with type 2 DM is
      characterized by elevated triglycerides, low levels of high-density lipoprotein
      cholesterol, and small dense low-density lipoprotein cholesterol (LDLC) particles
      and is believed to be a key factor promoting atherosclerosis in these patients.
      Both primary and secondary prevention studies have provided ample evidence that
      aggressive statin therapy reduces cardiovascular end points in patients with DM.
      In all persons with DM, current treatment guidelines recommend reduction of LDLC
      to less than 100 mg/dL, regardless of baseline lipid levels. Lowering LDLC to
      less than 70 mg/dL may provide even greater benefits, particularly in very high
      risk patients with DM and coronary heart disease.

PMID- 17547841
TI  - Glycotoxins in the diet promote diabetes and diabetic complications.
AB  - Oxidant stress underlies diabetes and diabetic complications, including
      cardiovascular, renal, and retinal disease. Advanced glycation end products
      (AGEs), or glycotoxins, are a significant contributor to oxidant stress in
      diabetes. The diet is a major, unrecognized source of AGEs. Importantly,
      reduction of dietary AGEs decreases circulating inflammatory markers in both
      diabetic patients and prediabetic patients and complications in animal models.
      This beneficial outcome requires only a 50% decrease in dietary AGEs, making this
      necessary intervention practical and inexpensive.

PMID- 17547842
TI  - Inflammatory mechanisms of diabetic complications.
AB  - Activation of inflammatory processes may contribute to the development of type 2
      diabetes mellitus. In addition, inflammation appears to be a major mechanism
      responsible for vascular damage leading to the clinically well-recognized
      complications of diabetes. Inflammatory cytokine and chemokine mediators released
      from visceral fat contribute to atherosclerotic plaque formation and increased
      risk for myocardial infarction and stroke. Activation of growth factors and
      adhesion molecules may promote the movement of inflammatory cells into the renal
      microvasculature, predisposing to the development of diabetic nephropathy.
      Emerging evidence also indicates that markers of inflammation are associated with
      the more severe forms of diabetic retinopathy. Future approaches to the treatment
      of diabetic complications may involve regulation of inflammatory processes,
      specifically targeting factors that contribute to vascular damage.

PMID- 17547843
TI  - Exhaled nitric oxide in asthma: "everything we have always wanted" or "not quite
      ready for prime time?".

PMID- 17547844
TI  - Stevens-Johnson syndrome and toxic epidermal necrolysis.
AB  - Since their first descriptions in 1922 and 1948, respectively, Stevens-Johnson
      syndrome and toxic epidermal necrolysis (SJS/TEN) have become recognized as
      manifestations--with different severity--of the same disease process along a
      spectrum of illness. Even today, decades after their description, there is still
      disagreement about when a particular bullous disease evolves from erythema
      multiforme to SJS/TEN. There is no disagreement, however, about the potentially
      life-threatening nature of the disease. Many cases are misdiagnosed, especially
      in their early stages. In this paper we address our current understanding of this
      disease spectrum and discuss both accepted and more controversial modes of
      therapy.

PMID- 17547845
TI  - Mastocytosis: advances in diagnosis and treatment.
AB  - Mastocytosis is characterized by pathologic mast cell accumulation and activation
      in tissues. Establishment of objective histopathologic and molecular criteria for
      diagnosis of mastocytosis has allowed sensitive detection of mast cells with
      aberrant features in patients presenting with suspected mast cell activation
      symptoms. Frequent detection of the D816V c-kit tyrosine kinase mutation in
      mastocytosis has led to evaluation of small-molecular-weight tyrosine kinase
      inhibitors as mast cell cytoreductive agents. In vitro experiments, however,
      showed that mast cells carrying the D816V c-kit mutation were resistant to the
      prototypical tyrosine kinase inhibitor imatinib. Efficacy of newer generation
      tyrosine inhibitors in mast cell disease is currently being evaluated.

PMID- 17547846
TI  - What's new in blistering disorders?
AB  - From the characterization of new animal models for the study of disease
      pathogenesis, to the demonstration of new therapeutic modalities, many
      developments have revolutionized the field of autoimmune bullous diseases in the
      past several years. This review highlights many of the significant advances that
      have taken place in the diagnosis, pathogenesis, and treatment options for
      pemphigus, pemphigoid, epidermolysis bullosa acquisita, and immunoglobulin (Ig) A
      mediated bullous disorders.

PMID- 17547847
TI  - C1-inhibitor deficiencies (hereditary angioedema): where are we with therapies?
AB  - Hereditary angioedema, an autosomal dominant disorder, presents clinically as
      recurrent episodes of swelling. It results from either deficient production or
      function of C1 inhibitor. Acquired angioedema is associated with
      lymphoproliferative or autoimmune disease. Conventionally attenuated androgens
      and antifibrinolytics have been used for prophylaxis, both for the long term and
      presurgically. Fresh frozen plasma and plasma-derived C1 inhibitor concentrate
      have been used primarily for treatment of acute attacks. All have drawbacks in
      side effects or potential for infection transmission. New treatments (recombinant
      C1 inhibitor, icatibant, DX-88, and for acquired angioedema, rituximab) so far
      show good safety profiles. Early data suggest these may be effective treatment
      alternatives. The efficacy of current treatment and the potential held by newer
      agents that target specific elements in complement or kinin pathways are
      examined. Some agents are likely to have a wider role in treatment of other, more
      common, forms of angioedema.

PMID- 17547849
TI  - Plasmapheresis for chronic inflammatory demyelinating polyradiculoneuropathy.
AB  - Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an immune
      mediated disorder characterized by progressive or relapsing symmetrical motor or
      sensory symptoms and signs in more than one limb, developing over at least 2
      months. It may cause prolonged periods of disability and even death. Evidence
      from trials suggests that plasma exchange provides significant short-term benefit
      in about two thirds of patients with chronic inflammatory demyelinating
      polyradiculoneuropathy. This review evaluates the role of plasmapheresis in CIDP.

PMID- 17547850
TI  - The spectrum of multiple sclerosis.
AB  - Multiple sclerosis (MS) is the most common cause of chronic neurologic disability
      in young people. Genetic susceptibility and unidentified environmental triggers
      appear to be necessary in order to result in disease. MS is an extraordinarily
      complex trait with evidence of heterogeneity at clinical, pathologic, and
      therapeutic levels. Recent studies have not resolved the important question
      whether at a mechanistic level MS is a single disease with a wide spectrum of
      clinical expression, or whether it encompasses a group of separate diseases that
      share certain pathologic final common pathways. This question is important not
      only for helping to understand the causes of MS but also for designing and
      applying better treatments.

PMID- 17547851
TI  - Immunology of multiple sclerosis.
AB  - Multiple sclerosis (MS) is an autoimmune disease of the central nervous system
      (CNS) leading to demyelination, axonal damage, and progressive neurologic
      disability. The development of MS is influenced by environmental factors,
      particularly the Epstein-Barr virus (EBV), and genetic factors, which include
      specific HLA types, particularly DRB1*1501-DQA1*0102-DQB1*0602, and a
      predisposition to autoimmunity in general. MS patients have increased circulating
      T-cell and antibody reactivity to myelin proteins and gangliosides. It is
      proposed that the role of EBV is to infect autoreactive B cells that then seed
      the CNS and promote the survival of autoreactive T cells there. It is also
      proposed that the clinical attacks of relapsing-remitting MS are orchestrated by
      myelin-reactive T cells entering the white matter of the CNS from the blood, and
      that the progressive disability in primary and secondary progressive MS is caused
      by the action of autoantibodies produced in the CNS by -meningeal lymphoid
      follicles with germinal centers.

PMID- 17547852
TI  - Current management options in myasthenia gravis.
AB  - Myasthenia gravis has changed from being a frequently fatal condition with a
      reputation little better than motor neuron disease to a generally treatable
      condition over the previous century. However, the chronic, largely
      immunosuppressive treatment comes with the major problems of very slow response
      and of treatment-induced morbidity and mortality. -Myasthenia gravis is a model
      autoimmune disease of a model physiologic structure, so is well placed for trials
      of novel treatments with ramifications for autoimmunity generally. There are also
      good animal models, so specific approaches to reinduction of tolerance can be
      tested. Hope of future revolutions in treatment should not hinder efforts to
      better understand currently available therapies and a concerted approach to
      ameliorate the side effects of treatment.

PMID- 17547853
TI  - The role of environmental tobacco smoke in the origins and progression of asthma.
AB  - Exposure to environmental tobacco smoke (ETS) is a major source of indoor air
      pollution and causes adverse effects on the respiratory health of individuals
      with asthma. At least one third of children and adults with asthma are exposed to
      ETS on a regular basis. There is convincing evidence for a causal relationship
      between exposure to ETS and development of asthma in children and in nonsmoking
      adults. Exposure to ETS also worsens asthma control in children and nonsmoking
      adults who have established asthma. The mechanism by which ETS causes these
      harmful effects is not established but may involve genetic predisposition,
      impairment of lung development, and altered lung inflammatory responses.
      Workplace smoking restrictions and reduced smoking in the home may lower the
      prevalence of asthma, improve asthma control, and reduce the use of medical
      services in both children and adults who are exposed to ETS.

PMID- 17547854
TI  - Levalbuterol for asthma: a better treatment?
AB  - The purpose of this review is to determine whether the proinflammatory actions
      identified in vitro for (S)-albuterol provide a clinically significant
      therapeutic advantage for levalbuterol over racemic albuterol. Clinical trials
      evaluating the bronchodilation in chronic and acute asthma provide conflicting
      evidence. Older trials suggested an advantage for levalbuterol; however, the
      newer trials have failed to confirm those advantages. Although (S)-albuterol
      produces increased bronchial hyperresponsiveness in vitro and in animal models,
      this has not been consistently confirmed in clinical trials; however, the
      heterogeneity of the trials precludes definitive conclusions. Current clinical
      trials do not provide evidence of a substantial advantage of levalbuterol over
      racemic albuterol although the data are insufficient to determine whether subsets
      of the patient population might benefit from single isomer therapy.

PMID- 17547855
TI  - Efficacy of infliximab for luminal and fistulizing Crohn's disease and in
      ulcerative colitis.
AB  - Infliximab is arguably the first major advance in therapy for inflammatory bowel
      disease in more than a quarter of a century. Although it is important to
      distinguish efficacy from effectiveness, the data from clinical practice mirror
      those from randomized controlled trials. Infliximab has proven efficacious for
      luminal manifestations of Crohn's disease (CD) regardless of location. It also
      has proven efficacy in the subset of penetrating disease to the skin and perianal
      area, and it increases rates of steroid-free remission. These benefits are
      reflected in improved quality of life, with limited data showing that infliximab
      can decrease rates of hospitalization and CD-related surgery. Infliximab also has
      proven to be efficacious in patients with ulcerative colitis (UC) and has
      increased rates of steroid-free remission. Whether infliximab will have an impact
      on the risk of colorectal cancer in UC and Crohn's colitis has yet to be
      determined. The combination of strong evidence from large randomized controlled
      trials with substantial examination of use in the practice setting has moved
      biologic therapy with infliximab from novel to mainstream. In this review, the
      data for the efficacy of infliximab in controlled trials will be discussed in the
      context of real world effectiveness.

PMID- 17547856
TI  - Efficacy of infliximab for extraintestinal manifestations of inflammatory bowel
      disease.
AB  - Crohn's disease (CD) and ulcerative colitis (UC), collectively referred to as
      inflammatory bowel disease (IBD), are associated with extraintestinal
      manifestations (EIMs) in approximately 40% of patients. Infliximab, a chimeric
      monoclonal antibody to tumor necrosis factor-alpha, is effective for induction
      and maintenance of remission of CD and UC. The role of infliximab for EIMs
      related to IBD has been less studied, but it is likely as effective. The EIMs may
      run a course that parallels IBD activity or may present separately. The EIMs that
      parallel intestinal inflammation (eg, peripheral arthritis, pyoderma gangrenosum,
      erythema nodosum, and episcleritis) generally respond to infliximab. Therefore,
      treating patients with IBD who have one of these EIMs will more often than not
      improve the EIM. The EIMs that run a separate course from IBD are more difficult
      to treat. Ankylosing spondylitis (AS), uveitis, and primary sclerosing
      cholangitis (PSC) have variable responses to IBD medications. Infliximab is
      efficacious for uveitis and is approved by the US Food and Drug Administration
      for treatment of AS. The efficacy of infliximab for PSC is unknown. The dosing
      schedule of infliximab for IBD patients with EIMs should be induction doses with
      5 mg/kg at 0, 2, and 6 weeks followed by every 8 weeks. Whether long-term
      infliximab therapy is necessary to maintain remission of EIMs, as in the case of
      IBD, has not been established.

PMID- 17547857
TI  - Pharmacoeconomics and quality of life of current and emerging biologic therapies
      for inflammatory bowel disease.
AB  - The development of biologic therapies for Crohn's disease and ulcerative colitis
      has profoundly affected the treatment of these diseases. The impact of these
      novel therapies has been tremendous in terms of their ability to cause clinical
      improvement in symptoms and endoscopic and histologic evidence of healing, as
      well as improvements in quality of life. However, the success of these new
      remedies comes with a significant price tag. In the current cost-containment
      environment of health care, it is essential to evaluate the impact of these novel
      and promising therapies on health care resource utilization, employment
      productivity, and quality of life. Despite the high cost of these new
      medications, they may result in a net cost savings through their ability to
      induce remission in the sickest of inflammatory bowel disease (IBD) patients,
      thereby averting the large expenditures associated with hospitalization and
      surgery. Likewise, by improving patients' physical symptoms, emotional well
      being, and quality of life, biologic agents have the potential to reduce much of
      the unemployment, missed work, and disability through which IBD patients suffer.
      In a disease with an early age of onset and a chronic course with normal life
      expectancy, reducing morbidity and improving quality of life should be important
      measures of treatment success. Biologic therapies for IBD hold significant
      promise in this regard, allowing clinicians to achieve lasting remission in
      patients who are unresponsive to conventional therapies. Comparison of the costs
      and benefits of biologic therapies with conventional treatments for IBD is
      complicated by the need to assess the downstream effects of an intervention. For
      example, corticosteroids are inexpensive and very effective for induction of
      remission, but they come with significant long-term complications, such as
      osteoporosis, cataracts, impaired glucose tolerance, and poor wound healing,
      which must be taken into account when assessing their true cost as a maintenance
      medication. We do not yet have enough experience with biologic therapies to
      evaluate their potential to prevent or create future costs associated with
      adverse effects. However, as we move forward with our knowledge of biologic
      agents, an understanding of the economic and quality-of-life implications of
      these innovative therapies is crucial for patients, clinicians, and third-party
      payers alike.

PMID- 17547858
TI  - Current and Future Anti-TNF Therapy for Inflammatory Bowel Disease.
AB  - Anti-tumor necrosis factor-alpha (anti-TNF) therapy has become a very important
      modality in the treatment of patients with inflammatory bowel disease. A number
      of anti-TNF medications have been investigated for this purpose, many via
      randomized controlled trials. Infliximab, the most studied of these agents, has
      shown impressive efficacy in the treatment of luminal and fistulizing Crohn's
      disease, as well as ulcerative colitis. Adalimumab and certolizumab have shown
      similar efficacy in Crohn's disease but have not yet been studied in ulcerative
      colitis. Less impressive results were seen in randomized controlled trials
      involving CDP-571, etanercept, or onercept for patients with Crohn's disease.
      Thalidomide and CNI-1493 have been evaluated only preliminarily in small, open
      label pilot studies in patients with Crohn's disease. The future of anti-TNF
      therapy in inflammatory bowel disease is very bright, as exciting new
      developments continue to be made at a rapid pace.

PMID- 17547859
TI  - Treatment of Perianal Fistula and Abscess: Crohn's and Non-Crohn's.
AB  - The management of perianal abscesses and fistulas is relatively straightforward
      in most cases and based on a sound knowledge of the anatomy of the anorectum and
      adherence to established medical and surgical principles. Asymptomatic fistulas
      should not be treated, whereas abscesses require surgical drainage under general
      anesthesia. Fistula treatment includes drainage of any associated sepsis and
      eradication of the fistula track to prevent recurrence while preserving sphincter
      integrity. A small percentage of anal abscesses and fistulas are complex and very
      challenging to manage, particularly in conditions such as rectovaginal fistulas
      and abscesses and/or fistulas complicating Crohn's disease. Treatment strategies
      in these situations rely on an accurate clinical assessment of the degree of
      rectal inflammation and perianal pathology. Treatment should combine aggressive
      medical therapy (antibiotics, immunomodulators, and anti-tumor necrosis factor
      antibody treatment) and minimal surgical interventions. Patients with proctitis
      have a significantly lower healing rate and a significantly higher complication
      rate with aggressive surgical interventions.

PMID- 17547860
TI  - Functional disorders of defecation: evaluation and treatment.
AB  - Functional disorders of defecation are common and often overlap with slow-transit
      constipation. They are comprised of functional obstructive conditions such as
      dyssynergic defecation, as well as structural obstructive conditions such as
      rectal prolapse, excessive perineal descent, and rectocele. Evaluation includes
      detailed history and rectal and pelvic exam together with physiologic tests such
      as anorectal manometry, balloon expulsion test, defecography, and MRI. Treatment
      involves several medical, behavioral, and surgical approaches. Recently,
      randomized controlled trials have shown that biofeedback therapy is an effective
      treatment for dyssynergic defecation. Stapled transanal rectal resection appears
      to be a promising technique for treating defecation disorders associated with
      rectocele, excessive perineal descent, and mucosal intussusception, but
      controlled trials are lacking.

PMID- 17547861
TI  - Microscopic colitis.
AB  - As the diagnosis of microscopic colitis (MC) is made on the basis of histologic
      criteria, it is crucial to render an accurate microscopic interpretation.
      Features include 20 or more lymphocytes per 100 epithelial cells, mixed lamina
      propria inflammatory infiltrate, and preservation of crypt architecture for both
      lymphocytic and collagenous colitis (CC). CC is further characterized by a
      collagen band at least 10 mum thick. Although the pathogenesis of MC is poorly
      understood, medication-induced toxicity to the colonic mucosa is important to
      recognize, as medication cessation leads to prompt improvement. If MC is mild,
      symptomatic treatment is all that is needed, because some cases are self
      limiting. Budesonide, 9 mg daily for at least 8 weeks, is the best documented
      treatment of choice for more severe or protracted cases. A 75% response rate has
      been reported; however, when treatment is discontinued, relapse is common, and
      longer-term tapering dose therapy often is necessary. There are disadvantages and
      no advantage to other forms of steroid therapy. Cholestyramine, bismuth, and 5
      aminosalicylate derivatives appear to be less efficacious but are reasonable
      therapeutic options for less severe cases. Use of immunosuppressant therapy such
      as azathioprine or 6-mercaptopurine should be highly restricted because MC is a
      benign condition that does not result in other complications. Probiotic therapy
      with Lactobacillus acidophilus and Bifidobacterium animalis has not been shown to
      be effective in reducing bowel frequency. Surgical diversion of the fecal stream
      can control diarrhea and improve histology but is very rarely indicated and
      should be reserved for highly selected cases of severely symptomatic steroid
      refractory MC.

PMID- 17547862
TI  - Acute and chronic megacolon.
AB  - Megacolon, defined as dilation of the abdominal colon, may occur acutely or in a
      chronic form. Acute megacolon that occurs in association with severe inflammation
      of the colon is known as toxic megacolon, whereas acute megacolon without obvious
      colonic disease is known as Ogilvie's syndrome. The pathophysiology and
      management of toxic megacolon, Ogilvie's syndrome, and chronic megacolon in
      adults differ significantly, and it is critically important to distinguish among
      these entities. Toxic megacolon is a medical emergency that requires coordinated
      intensive medical and surgical management. In addition to vigorous resuscitation
      with fluids, electrolytes, and blood products, medical treatment consists of
      parenteral corticosteroids, broad-spectrum antibiotics, and close monitoring of
      the patient. Surgical intervention is required if there is no improvement, or
      deterioration after 12 to 24 hours of intensive medical management, or if there
      is evidence of colon perforation. Ogilvie's syndrome usually occurs in
      hospitalized patients with serious underlying medical or surgical illnesses.
      Management is directed at preventing ischemia and perforation of the distended
      colon. Supportive therapy includes nasogastric suction, correction of fluid and
      electrolyte imbalances, stopping potentially aggravating medications, and
      decompressing the colon with a rectal tube and positional changes. Intravenous
      neostigmine is the only pharmacologic agent of proven efficacy; colonoscopic
      decompression is an alternative in patients who do not respond to neostigmine or
      who have conditions that contraindicate its use. Daily oral administration of
      polyethylene glycol electrolyte solutions appears to decrease the relapse rate
      after initial decompression is achieved. Chronic megacolon in adults represents
      advanced colon failure that does not respond to pharmacologic stimulation. Goals
      of therapy are to cleanse the colon, prevent impaction, and minimize stool volume
      and gas buildup. For patients with disabling symptoms, surgical exclusion of the
      colon, decompression and antegrade enemas via cecostomy, or subtotal or segmental
      resection may be palliative.

PMID- 17547863
TI  - Diverticular disease: update.
AB  - Diverticular disease is an extremely common disease entity in our society. The
      major complication of diverticular disease, diverticulitis, can have quite
      variable presentations. In the acute setting, treatment is divided into
      nonsurgical (conservative) or surgical therapy. Cases of mild or "uncomplicated"
      disease benefit from a conservative approach involving antibiotic therapy. With
      more severe or "complicated" presentations (abscess, phlegmon, obstruction,
      fistula, or peritonitis), a more aggressive approach may involve percutaneous
      abscess drainage or urgent surgical therapy. This also may be required after a
      failed initial attempt at medical management. The decision regarding elective
      surgery after successful medical management of diverticulitis is more
      complicated. The primary goal is to minimize disease recurrence with as little
      morbidity as possible while maintaining a high quality of life. Recent evidence
      challenges indications for elective surgery. However, data on the natural history
      of recurrent diverticulitis are not clear enough to support altering current
      surgical guidelines. In addition, the increasing use of minimally invasive
      techniques with favorable outcomes for sigmoid colectomy must be considered.
      Prior to offering elective colectomy for diverticulitis, it remains important to
      individualize each case, giving special consideration to age, symptomatology, and
      recurrence. Ultimately, the decision for elective surgery is made by both the
      surgeon and a well-informed patient.

PMID- 17547864
TI  - Discussion: 'Assessing physical fitness' by Heimmel et al.

PMID- 17547866
TI  - Use of amniotic fluid index in diabetic patients.

PMID- 17547867
TI  - Can uterine rupture in patients attempting vaginal birth after cesarean delivery
      be predicted?

PMID- 17547869
TI  - Sizing up our teens.

PMID- 17547871
TI  - Asymptomatic bacterial vaginosis: is it time to treat?

PMID- 17547872
TI  - Can maternal dietary intervention modify Doppler parameters of the fetoplacental
      circulation?

PMID- 17547873
TI  - Risk factors for antepartum and intrapartum stillbirth: a population-based study.
AB  - To examine disparities in risk factors for stillbirths and its occurrence in the
      antepartum versus intrapartum periods. A population-based, cross-sectional study
      using data on women that delivered singleton births between 20 and 43 weeks in
      Missouri (1989-1997) was conducted (n = 626,883). Hazard ratios and 95%
      confidence intervals were derived from regression models and population
      attributable fractions were estimated to examine the impact of risk factors on
      stillbirth. Among African Americans, risks of antepartum and intrapartum
      stillbirth were 5.6 and 1.1 per 1,000 singleton births, respectively; risks among
      whites were 3.4 and 0.5 per 1,000 births, respectively. Maternal age > or = 35
      years, lack of prenatal care, prepregnancy body mass index (BMI) > or = 30 kg/m2,
      and prior preterm or small-for-gestational age birth were significantly
      associated with increased risk for antepartum stillbirth among whites, but not
      African Americans. BMI < or = 18.5 kg/m2 was associated with antepartum and
      intrapartum stillbirth among African Americans, but not whites. The presence of
      any congenital anomaly, abruption, and cord complications were associated with
      antepartum stillbirth in both races. Premature rupture of membranes was
      associated with intrapartum stillbirth among whites and African Americans, but
      intrapartum fever was associated with intrapartum stillbirth among African
      Americans. These risk factors were implicated in 54.9% and 19.7% of antepartum
      and intrapartum stillbirths, respectively, among African American women, and in a
      respective 46.6% and 11.9% among white women. Considerable heterogeneity in risk
      factors between antepartum and intrapartum stillbirths is evident. Knowledge on
      timing of stillbirth specific risk factors may help clinicians in decreasing
      antepartum and intrapartum stillbirth risks through monitoring and timely
      intervention.

PMID- 17547874
TI  - To the point: medical education reviews--providing feedback.
AB  - Formative feedback is an essential component of effective teaching and learning.
      Without it, the learner flounders. Furthermore, the Liaison Committee on Medical
      Education requires formative feedback within the clerkship and specifies that
      students must have the time and ability to remediate deficiencies before
      completing the clerkship. Few articles in the medical literature address how to
      give effective feedback. However, the themes within these articles are
      consistent. Formative feedback should be an interactive activity between the
      teacher and learner. Feedback must be approached with mutual respect and should
      be provided in a safe environment. Quality feedback is timely, specific to the
      situation, constructive, based on direct observation and nonjudgmental. With
      effective feedback, learners (and teachers) can discover what to improve, as well
      as which behaviors and skills to reinforce and augment. Learners appreciate and
      request specific feedback. In addition, learners tend to rate teachers who
      provide feedback more highly than they rate teachers who do not provide feedback.
      This article in the "To the Point" series will focus on the components of
      effective feedback and provide a practical and effective approach to giving
      feedback.

PMID- 17547875
TI  - Expectant management of severe preeclampsia remote from term: patient selection,
      treatment, and delivery indications.
AB  - Severe preeclampsia that develops at <34 weeks of gestation is associated with
      high perinatal mortality and morbidity rates. Management with immediate delivery
      leads to high neonatal mortality and morbidity rates and prolonged
      hospitalization in the neonatal intensive care unit because of prematurity.
      Conversely, attempts to prolong pregnancy with expectant management may result in
      fetal death or asphyxial damage in utero and increased maternal morbidity. Since
      1990, 2 randomized trials and several observational studies have evaluated the
      benefits vs risks of expectant management of severe preeclampsia at <34 weeks of
      gestation. These studies included 1677 women with gestational age between 24 and
      34 weeks and 115 women with gestational age of <25 weeks (overlap in some
      studies). The results of these studies suggest that expectant treatment in a
      select group of women with severe preeclampsia between 24 0/7 and 32 6/7 weeks of
      gestation in a suitable hospital is safe and improves neonatal outcome. For
      gestational age of <24 0/7 weeks, expectant treatment was associated with high
      maternal morbidity with limited perinatal benefit. Based on the review of these
      studies and our own experience, recommendations are made for the selection of the
      appropriate candidates for expectant treatment, criteria for maternal-fetal
      monitoring, and targets for delivery. Finally, we provide information regarding
      maternal counseling based on maternal condition and fetal gestational age at time
      of diagnosis.

PMID- 17547876
TI  - A randomized trial of metronidazole in asymptomatic bacterial vaginosis to
      prevent the acquisition of sexually transmitted diseases.
AB  - OBJECTIVE: The purpose of this study was to determine whether treatment of
      bacterial vaginosis (BV) decreases the incidence of sexually transmitted diseases
      (STDs). STUDY DESIGN: Women with asymptomatic BV were studied prospectively to
      determine the effect of treatment of BV for the prevention of STD. Women were
      assigned randomly to observation or treatment and prophylaxis with intravaginal
      metronidazole gel. Women were screened monthly for STDs. RESULTS: Women who were
      assigned randomly to receive metronidazole gel had a significantly longer time to
      the development of STDs compared with women in the observation group (P = .02).
      The 6-month STD rate was 1.58 per person-year (95% CI, 1.29, 1.87) for women in
      the metronidazole gel group vs 2.29 per person-year (95% CI, 1.95, 2.63) for
      women in the observational group. The difference in STD rates was driven by a
      significant difference in the number of chlamydial infections (P = .013).
      CONCLUSION: Treatment and twice-weekly prophylactic use of intravaginal
      metronidazole gel resulted in significantly fewer cases of chlamydia.

PMID- 17547877
TI  - Uterine artery embolization versus hysterectomy in the treatment of symptomatic
      uterine fibroids: 2 years' outcome from the randomized EMMY trial.
AB  - OBJECTIVE: The purpose of this study was to compare the 2 years' efficiency of
      uterine artery embolization (UAE) with hysterectomy in the treatment of
      menorrhagia caused by uterine fibroids in a randomized controlled trial. STUDY
      DESIGN: Twenty-eight Dutch hospitals recruited patients with uterine fibroids and
      menorrhagia, who were eligible for hysterectomy. Patients were randomized to UAE
      or hysterectomy. The primary endpoint was if UAE could avoid a subsequent
      hysterectomy in at least 75% of cases. Secondary endpoints were changes in pain,
      bulk-related complaints, and uterine and dominant fibroid volume reduction.
      RESULTS: One hundred seventy-seven patients were randomized to UAE (n = 88) or
      hysterectomy (n = 89). Two years after treatment 23.5% of UAE patients had
      undergone a hysterectomy. There were no significant differences in improvement
      compared to baseline in pain and bulk-related complaints. Uterine and dominant
      fibroid volume reduction in UAE patients was 48.2% and 60.5%, respectively.
      CONCLUSION: UAE is a valuable alternative treatment for symptomatic uterine
      fibroids. Nevertheless, when patients seek for certainty on the cessation of
      bleeding problems, a hysterectomy remains the treatment of choice.

PMID- 17547878
TI  - Evaluation of physical fitness in an ambulatory setting.
AB  - OBJECTIVE: The purpose of this study was to perform a brief physical fitness
      evaluation for ambulatory gynecologic patients and to determine whether a woman's
      perceived fitness level corresponded to her actual level. Except for patient
      report of exercise activity, no objective measures of fitness are assessed during
      annual gynecologic office visits. STUDY DESIGN: Written surveys and physical
      measurements were administered to 103 healthy women during their annual
      gynecologic visit. Patient self-report of fitness level, compared with actual
      fitness level determined by physical testing, was used as the main outcome
      measure. RESULTS: Physical fitness testing took 5-7 minutes to administer in a 3
      x 2.2-meter office area. The woman's report of physical fitness did not correlate
      with actual fitness; rather, percent body fat as calculated by Lange skinfold
      caliper correlated most accurately with overall fitness (correlation coefficient,
      -0.389). Body mass index was correlated less strongly with a coefficient of 
      0.274; surprisingly, the waist/hip ratio had the weakest correlation to fitness
      (correlation coefficient, -0.129). CONCLUSION: Patient report does not appear to
      correlate with actual physical fitness. Physicians may consider initiating an
      objective measure, such as body fat measurement as calculated by Lange skinfold
      calipers, to the routine examination.

PMID- 17547879
TI  - Untreated asymptomatic group B streptococcal bacteriuria early in pregnancy and
      chorioamnionitis at delivery.
AB  - OBJECTIVE: The objective of the study was to determine the frequency of adverse
      pregnancy outcomes in women with untreated asymptomatic group B beta-hemolytic
      streptococcal (GBS) bacteriuria during pregnancy. STUDY DESIGN: In this
      retrospective cohort, all women with antepartum GBS bacteriuria in a research
      registry were included. Controls were women with negative urine cultures. The
      frequency of chorioamnionitis was compared between groups. Chorioamnionitis was
      defined as intrapartum fever, fetal tachycardia, and histologic inflammation of
      the membranes. RESULTS: One hundred twenty-two women with bacteriuria (study
      group) and 183 women with negative antepartum cultures (controls) were included.
      There were no differences in demographic characteristics between the groups.
      Thirty-one women (10.2%) had chorioamnionitis. Untreated GBS bacteriuria was
      associated with chorioamnionitis after controlling for confounding variables,
      adjusted odds ratio 7.2 (95% confidence interval 2.4 to 21.2). There was also a
      significant positive rank correlation between increasing colony count of GBS
      bacteriuria and increasing grade of chorioamnionitis (P = .02). CONCLUSION:
      Untreated antepartum GBS bacteriuria is associated with chorioamnionitis.

PMID- 17547880
TI  - Variation in the rates of operative delivery in the United States.
AB  - OBJECTIVES: This study was undertaken to examine the national and regional rates
      of operative delivery among almost one quarter million births in a single year in
      the nation's largest healthcare delivery system, using variation as an arbiter of
      the quality of decision making. STUDY DESIGN: We compared the variation in rates
      of primary cesarean and operative vaginal delivery in facilities of the Hospital
      Corporation of America during the year 2004. RESULTS: In 124 facilities
      representing almost 220,000 births during a 1-year period, the primary cesarean
      and operative vaginal delivery rates were 19% +/- 5% (range 9-37) and 7% +/- 4%
      (range 1-23). Within individual geographic regions, we consistently found
      variations of 200-300% in rates of primary cesarean delivery and variations
      approximating an order of magnitude for operative vaginal delivery. CONCLUSION:
      Within broad upper and lower limits, rates of operative delivery in the United
      States are highly variable and suggest a pattern of almost random decision
      making. This reflects a lack of sufficient reliable, outcomes-based data to guide
      clinical decision making.

PMID- 17547881
TI  - Modified classification of Gram-stained vaginal smears to predict spontaneous
      preterm birth: a prospective cohort study.
AB  - OBJECTIVE: The purpose of this study was to identify women at risk of spontaneous
      preterm birth through a 4-category Gram-stained vaginal smear method, not
      restricted to bacterial vaginosis. STUDY DESIGN: This was a prospective cohort
      study correlating Gram-stained vaginal smears in early pregnancy with spontaneous
      preterm birth. Smears were categorized as 'normal,' 'bacterial vaginosis-like,'
      'grade I-like' (atypical gram-positive rods) or 'purulent grade I' (lactobacilli
      dominated smears showing heavy leukorrhea of unknown cause). RESULTS: Normal
      microflora were associated with a 4-fold decreased risk (95%CI 0.1-0.6, P < .001)
      of spontaneous preterm birth and an abnormal Gram stain with an overall adjusted
      odds ratio of 5.2 (95%CI 1.8-14.5, P < .001). The sensitivity of vaginal smear
      diagnosis for preterm birth increased from 25% with conventional scoring up to
      70% with these modified criteria. CONCLUSION: Accounting for atypical gram
      positive bacteria and neutrophils on Gram-stained vaginal smears may identify a
      larger proportion of women at risk of preterm birth compared to diagnosis of
      bacterial vaginosis alone.

PMID- 17547882
TI  - Changes in prepregnancy body mass index between the first and second pregnancies
      and risk of large-for-gestational-age birth.
AB  - OBJECTIVE: The objective of our study was to determine whether changes in
      prepregnancy body mass index (BMI) between the first 2 pregnancies is associated
      with increased risk for large-for-gestational-age (LGA) birth in the second
      pregnancy. STUDY DESIGN: A population-based, retrospective cohort analysis was
      performed using the Missouri 1989-1997 longitudinally linked data. Women with the
      first 2 consecutive singleton live births (n = 146,227) were analyzed. BMI
      (kilograms per square meter) was categorized as underweight (less than 18.5),
      normal (18.5 to 24.9), overweight (25 to 29.9), and obese (30 or greater), and
      LGA was defined as gestational age-specific birthweight greater than the 90th
      centile. Multivariate logistic regression analysis was used to estimate the odds
      ratio (OR) with 95% confidence interval (CI). Population attributable fraction
      for LGA births was calculated. RESULTS: Compared to women with normal BMI in
      their first and second pregnancies, overweight-overweight (OR 1.7, 95% CI 1.6,
      1.8) and obese-obese (OR 2.3, 95% CI 2.2, 2.4) women in their first and second
      pregnancies were at increased risk of LGA births. Any increase in BMI from normal
      to obese between pregnancies increased LGA risk (OR 1.6 to 2.0), whereas any
      decrease in BMI from obese to normal attenuated the risk (OR 1.3 to 1.7). 17.1%,
      13.2%, and 7.6% of LGA births are likely preventable had BMI not increased from
      first pregnancy underweight, normal, and overweight, respectively. CONCLUSION: In
      comparison with women with normal BMI in both pregnancies, any increase or
      decrease in prepregnancy BMI between normal and obese is associated with
      increased risk of LGA birth. A modification in the risk of LGA births by long
      term maternal BMI status or maternal genetic factors appears likely.

PMID- 17547883
TI  - Is the association of maternal smoking and pregnancy-induced hypertension
      dependent on fetal growth?
AB  - OBJECTIVE: The risk of pregnancy-induced hypertension (PIH) is decreased by
      smoking, but the mechanisms remain unclear. Our objective was to determine
      whether this association is dependent on decreased fetal growth. METHODS: A
      population-based, retrospective cohort study in the United States was performed
      consisting of nulliparous women who delivered a singleton birth (n = 8,025,295)
      between 1995 and 2002. Fetal growth was defined as birthweight for gestational
      age and characterized as less than 1, 1-2, 3-4, 5-9, 10-19, ..., 90 or greater
      centiles. Risk and relative risk of PIH before and after adjusting for
      confounders were estimated. RESULTS: Smoking was associated with decreased risk
      of PIH with up to a 46% decreased risk of PIH for growth-restricted babies (less
      than the 10th centile). This association, however, decreased with increasing
      birthweight centile and was nonsignificant at 20th or greater centile among heavy
      smokers, at 60th or greater centile for moderate, and 80th or greater centile for
      light smokers. CONCLUSION: Smoking was primarily associated with decreased risk
      of PIH among growth-restricted babies.

PMID- 17547884
TI  - ANGELS and University of Arkansas for Medical Sciences paradigm for distant
      obstetrical care delivery.
AB  - OBJECTIVE: This article describes the process by which the Arkansas Medicaid
      Program, the University of Arkansas for Medical Sciences (the state's only
      academic health center), and Arkansas' practicing physicians are collaborating to
      improve the process of perinatal regionalization by providing access to
      expertise, education, and support of maternal-fetal medicine specialists. The
      described ANGELS model encourages replication among other programs that wish to
      improve perinatal regionalization attempts in their service areas. STUDY DESIGN:
      Through this unique collaboration, ANGELS is composed of 5 distinctive elements:
      a statewide telemedicine and clinic network, an education and support program for
      obstetric providers, case management services, a 24-hour Call Center, and an
      evidence-based guidelines development and distribution network. RESULTS: Since
      Arkansas has undertaken perinatal regionalization, technology has allowed the
      state's only group of board-certified maternal-fetal medicine specialists,
      located centrally in Little Rock, to provide real-time clinical support to
      physicians, as well as consultation or direct care to patients statewide.
      CONCLUSION: ANGELS' continued efforts have the potential to significantly improve
      perinatal care in rural areas throughout the state, while the cost of maternal
      and fetal health care could decline. The program's design, although unique, can
      be replicated elsewhere to encourage perinatal regionalization.

PMID- 17547885
TI  - Trial of labor and vaginal birth after cesarean section in patients with uterine
      Mullerian anomalies: a population-based study.
AB  - OBJECTIVE: The aim of our study was to determine the success rate of vaginal
      birth after cesarean section among patients with Mullerian anomalies in
      comparison to the success rate of vaginal birth after cesarean section in
      patients with normal uterus with emphasis on the rate of uterine rupture. STUDY
      DESIGN: A retrospective population-based study was designed, including all
      patients with a previous cesarean section that attempted vaginal birth after
      cesarean section during the study period. Women with known Mullerian anomalies
      were included in the study group. The control group consisted of women with
      normal uterus. The rates of vaginal birth after cesarean section, uterine
      rupture, maternal morbidity, and perinatal outcome were compared between the
      groups. RESULTS: Of 5571 eligible patients, 165 (2.96%) had Mullerian anomalies.
      The rate of vaginal birth after cesarean section was significantly lower among
      patients with Mullerian anomalies than in patients with normal uterus, 37.6%
      (62/165) vs 50.7% (2740/5406), respectively (P = .0009). During the study period,
      there were 10 cases of uterine rupture, all in patients with normal uterus. The
      major indication for repeated cesarean delivery among Mullerian anomalies
      patients was malpresentation, 58.3% (60/103) vs 14.4% (385/2666) in patients with
      normal uterus (P < .001). CONCLUSION: A trial of vaginal birth after cesarean
      section in patients with uterine Mullerian malformations and cephalic
      presentation is not associated with a higher rate of maternal morbidity and
      uterine rupture.

PMID- 17547886
TI  - Comparing mechanical fetal response during descent, crowning, and restitution
      among deliveries with and without shoulder dystocia.
AB  - OBJECTIVE: Previous computer simulations of shoulder dystocia (SD) explored the
      effect of SD itself on the mechanical response of the fetus. Our objective was to
      perform a mechanical simulation study to explore the variations in fetal response
      during routine, unilateral SD (USD), and bilateral SD (BSD) deliveries. STUDY
      DESIGN: Using a biofidelic birthing simulator, we performed 30 experiments
      mimicking passage of the fetus through the pelvis. For routine deliveries, we
      engaged the fetal head and allowed it to progress through cardinal movements
      using typical uterine contraction forces. Deliveries stopped when the head
      restituted externally to left occiput anterior (LOA) position. The identical
      procedure was repeated for USD deliveries, except we obstructed the anterior
      shoulder on the symphysis pubis; for BSD, the posterior shoulder was also
      impacted on the sacral promontory. For each delivery we continuously measured
      head rotation, brachial plexus (BP) stretch and neck extension, selecting peak
      values for analysis. Maximum rotation, BP stretch, and extension were compared
      among groups using analysis of variance, with P < .05 considered significant.
      RESULTS: Among routine, USD, and BSD deliveries, mean peak BP stretch varied
      between 10% and 21%, rotation varied between 70 degrees and 77 degrees, and
      extension varied between 6% and 18%. Greatest stretch occurred in the posterior
      BP during descent in non-SD deliveries, whereas anterior BP stretch, rotation,
      and extension were similar among the 3 types of deliveries. CONCLUSION:
      Quantifiable mechanical response occurs in routine and SD deliveries. Posterior
      BP stretch is significantly longer for routine deliveries than either USD or BSD
      deliveries. By itself, shoulder dystocia does not pose additional risk of
      brachial plexus stretch over routine deliveries.

PMID- 17547887
TI  - Live birth patterns among human immunodeficiency virus-infected women before and
      after the availability of highly active antiretroviral therapy.
AB  - OBJECTIVE: The objective of the study was to investigate the relationship between
      human immunodeficiency virus (HIV) infection and childbearing before and after
      the availability of highly active antiretroviral therapy (HAART). METHODS:
      Enrollment in the Women's Interagency HIV study took place in 1994-1995 (pre
      HAART era) and again in 2001-2002 (HAART era). Live birth rates prior to
      enrollment were compared between treatment era cohorts for HIV-infected and HIV
      uninfected women aged 15-44 years using Poisson regression. For HIV-infected
      women, we included live births between HIV diagnosis date and study entry; the
      HAART era cohort included only women diagnosed with HIV in 1996 and afterward.
      RESULTS: Among HIV-infected women, the HAART era live birth rate was 150% higher
      than in the pre-HAART era (P = .001) vs a 5% increase among HIV-uninfected women.
      The rate of increase in live birth rate was higher for women > or = 35 years old
      (vs younger than 25 years, P = .02), and with more than a high school education
      (vs. less than high school, P = .05). CONCLUSION: The availability of effective
      therapeutic interventions has had a profound impact on child-bearing among HIV
      infected women.

PMID- 17547888
TI  - Increasing use of antidepressants in pregnancy.
AB  - OBJECTIVE: The purpose of this study was to quantify the rate of exposures to
      antidepressants during pregnancy in a large cohort of women. STUDY DESIGN: This
      was a retrospective cohort study of 105,335 pregnancies among women enrolled in
      Tennessee Medicaid from 1999-2003. Pregnancies were classified according to
      antidepressant exposures during pregnancy using previously validated computerized
      pharmacy records linked with birth certificates. RESULTS: During the study
      period, 8.7% of women giving birth had exposure to any antidepressant; 6.2% had
      exposure to a selective serotonin reuptake inhibitor. Maternal age > 25 years (P
      < .0001), white race (P < .0001), and education > 12 years (P = .008) were
      significant predictors of antidepressant exposure. The proportion of pregnancies
      with antidepressant use increased from 5.7% of pregnancies in 1999 to 13.4% of
      pregnancies in 2003 (p < .0001). The increase was mostly accounted for by
      increases in selective serotonin reuptake inhibitor exposures. CONCLUSION: There
      is an urgent need for further studies that better quantify the fetal consequences
      of exposure to antidepressants.

PMID- 17547889
TI  - Stage III endometrial cancer: preoperative predictability, prognostic factors,
      and treatment outcome.
AB  - OBJECTIVE: The survival rate for the most common gynecologic cancer, endometrial
      cancer, has fallen significantly in the last 25 years. Stage III (International
      Federation of Gynecology and Obstetrics) disease accounts for most of the deaths.
      We evaluated prognostic factors, treatment-related survival, and routinely used
      assessments for identifying stage III disease before the operation. STUDY DESIGN:
      The data for patients with endometrial cancer stage III (n = 101) who had been
      treated at the McGill University Health Center between 1989 and 2003 were
      analyzed. RESULTS: Stage IIIA, IIIB, and IIIC tumors accounted for 63%, 4%, and
      33% of the data, respectively. The cause-specific survival at 2, 3, and 5 years
      was 82%, 77%, and 67%, respectively. In multivariate analysis with an adjustment
      for the standard prognostic variables, the final tumor grade, adnexal
      involvement, and lymph node dissection were significant predictors of cause
      specific survival (P = .001, .028, and .017, respectively). Of the preoperative
      investigations, an elevated CA-125 level was a significant predictor of cause
      specific survival in multivariate analysis (P = .029). CONCLUSION: An elevated CA
      125 level, adnexal involvement, the final tumor grade, and lymph node dissection
      were independent predictors for cause-specific survival.

PMID- 17547890
TI  - Effect of a cholesterol-lowering diet during pregnancy on maternal and fetal
      Doppler velocimetry: the CARRDIP study.
AB  - OBJECTIVE: The purpose of this study was to evaluate the effect of a low
      cholesterol low-saturated fat diet on Doppler indices in the fetus and mother.
      STUDY DESIGN: Two hundred ninety nonsmoking white women, aged 21-38 years,
      without previous pregnancy complications and carrying a single fetus were
      assigned randomly to continue their usual diet (control subjects; n = 149) or to
      adopt a low-cholesterol low-saturated fat diet (intervention group; n = 141) from
      gestational week 17-20 to birth. Doppler velocimetry of the umbilical artery and
      both uterine arteries were assessed at gestational weeks 24, 30, and 36. RESULTS:
      The physiologic gestational decrease in umbilical artery pulsatility index (PI)
      from week 24-30 was more pronounced in the intervention group, compared with the
      control group, with median values (interquartile range) of -0.17 (-0.29, -0.06)
      and -0.11 (-0.25, 0.01), respectively (P = .048). Assignment to the intervention
      diet did not influence the changes in mean PI value of the 2 uterine arteries (P
      = .3). The change in umbilical artery PI and mean PI value of the uterine
      arteries between weeks 24 and 36 were not significantly different between the 2
      groups (P = 1.0 and .2 respectively). CONCLUSION: Our study shows that a
      cholesterol-lowering diet during pregnancy may modify fetoplacental circulation
      in mid pregnancy.

PMID- 17547891
TI  - The effect of a matrix metalloproteinase inhibitor on inflammation-mediated
      preterm delivery.
AB  - OBJECTIVE: Several matrix metalloproteinases (MMP) have been implicated in
      preterm parturition. We hypothesized that administration of a MMP inhibitor would
      reduce the rate of inflammation-mediated preterm delivery and prolong gestation
      in a mouse model. STUDY DESIGN: We utilized an animal model of endotoxin-induced
      preterm delivery using timed pregnant C57Bl6 mice. Test animals received
      lipopolysaccharide (LPS) followed by the MMP inhibitor at 1 dose 12 hours after
      the LPS. Control mice received the same dose of LPS, followed by a control
      solution 12 hours after the LPS. The primary outcome was preterm delivery rate.
      RESULTS: Mice in the study group had a significantly lower rate of preterm
      delivery (44%) compared to 100% in the controls (P = .009). Furthermore, the
      latency between the administration of injection and delivery was also longer in
      the study group (means 28.3 hours, standard deviation 9.4 hours) than among
      controls (mean 15.7 hours, standard deviation 1.8 hours) (P < .001). CONCLUSION:
      Administration of an MMP inhibitor results in a decreased rate of inflammation
      mediated preterm delivery in this animal model.

PMID- 17547892
TI  - Betamethasone-related acute alterations of microtubule-associated proteins in the
      fetal sheep brain are reversible and independent of age during the last one-third
      of gestation.
AB  - OBJECTIVE: The purpose of this study was to examine whether glucocorticoid
      effects on neuronal cytoskeleton, which we have shown previously at 0.87
      gestation when the hypothalamo-pituitary-adrenal axis matures, are age-dependent
      and reversible. STUDY DESIGN: Fetal sheep received 3.3 microg kg(-1) h(-1)
      betamethasone (n = 10) or saline solution (n = 9) intravenously over 48 hours at
      0.75 gestation (ie, before the hypothalamo-pituitary-adrenal axis matures and
      when betamethasone is administered clinically). RESULTS: Betamethasone diminished
      microtubule-associated protein (MAP) 1B and 2 immunoreactivity in the frontal
      neocortex and caudate putamen (P < .05) and MAP2 in the hippocampus (P < .05),
      which is similar to the effects that are seen at 0.87 gestation. In agreement,
      the number of glucocorticoid receptors did not differ at both ages. Loss of MAP1B
      and MAP2 immunoreactivity was not accompanied by neuronal death and was
      reversible within 24 hours. CONCLUSION: Alteration of neuronal cytoskeletal
      proteins caused by antenatal betamethasone exposure is transient and independent
      of age during late gestation.

PMID- 17547893
TI  - The timing of nutrient restriction during rat pregnancy/lactation alters
      metabolic syndrome phenotype.
AB  - OBJECTIVE: Modulation of growth of intrauterine growth restricted (IUGR) newborns
      causes either adult obesity or normalization of body weight and fat. We
      investigated the impact of rapid versus delayed catch-up growth of IUGR offspring
      on glucose and lipid profiles. STUDY DESIGN: From 10 days to term gestation and
      through lactation, control pregnant rats received ad libitum food, whereas study
      rats were 50% food restricted. Cross-fostering techniques were used to examine
      effects of food restriction during pregnancy and/or lactation periods. Glucose
      and lipid profiles were determined in offspring at ages 1 day, 3 weeks, and 9
      months. RESULTS: Food restriction during pregnancy produced hypoglycemic IUGR
      pups. Those permitted rapid catch-up growth demonstrated adult obesity with
      insulin resistance (hyperglycemia/hyperinsulinemia) and hypertriglyceridemia.
      Conversely, IUGR exhibiting delayed catch-up growth demonstrated normal adult
      body weight and insulin deficiency (hyperglycemia/hypoinsulinemia) and elevated
      cholesterol levels as compared with controls. However, these adult offspring had
      higher glucose though similar insulin levels as control offspring nursed by food
      restricted dam. CONCLUSION: The timing and the rate of IUGR newborn catch-up
      growth causes markedly altered adult phenotypes. Although delayed newborn catch
      up growth may be beneficial in the prevention of adult obesity, there may be
      significant adverse effects on pancreatic function.

PMID- 17547894
TI  - Maternal leptin across pregnancy in women with small-for-gestational-age infants.
AB  - OBJECTIVE: We hypothesized that women with small-for-gestational-age (SGA)
      neonates would have lower concentrations of leptin compared to women with
      appropriately grown infants (AGA). STUDY DESIGN: This is a nested case-control
      study of normotensive nulliparous women. Cases (n = 28) delivered SGA < 10
      percentile and controls (n = 77) delivered AGA. Maternal plasma leptin
      concentrations were compared at 18, 28, and 40 weeks' gestation via repeated
      measures. RESULTS: Maternal leptin concentrations at 18 weeks were correlated
      with prepregnancy BMI (r = 0.69, P < .0001) and early pregnancy waist
      circumference (r = 0.59, P < .0001). After adjustment for maternal body
      composition, leptin was lower across pregnancy in women with SGA compared to AGA
      neonates (13.6 vs 15.2 ng/mL at 18 weeks; 13.6 vs 17.3 ng/mL at 28 weeks; 16.6 vs
      20.7 ng/mL at 40 weeks; P = .04). CONCLUSION: Maternal leptin was correlated with
      maternal adiposity; however, after adjustment for body composition, leptin was
      lower across pregnancy in women with SGA.

PMID- 17547895
TI  - Be prepared: Katrina's aftermath--health care in crisis.

PMID- 17547896
TI  - An evaluation of health care providers' sexual violence screening practices.
AB  - OBJECTIVE: To evaluate whether health care providers (HCPs) screen women and
      provide them with information about sexual violence and how women receive this
      information. STUDY DESIGN: A multiethnic sample of 945 low-income women recruited
      from family planning clinics responded to an anonymous survey regarding their
      discussions with HCPs about sexual violence. RESULTS: Forty-eight percent of
      women reported that they had been screened or given information about sexual
      violence by a HCP. Only 6% of women expressed discomfort with being screened, and
      more than 95% found the information given to them by HCPs to be helpful. Latina,
      less educated, and monolingual Spanish-speaking women were less likely to have
      been screened or provided information. CONCLUSION: Women find discussions of
      sexual violence by their HCPs to be helpful and nonintrusive. Educational,
      linguistic, and cultural factors appear to affect the likelihood that HCPs
      discuss sexual violence with their patients.

PMID- 17547897
TI  - Expectant management of preterm premature rupture of membranes and nonvertex
      presentation: what are the risks?
AB  - OBJECTIVE: Preterm premature rupture of membranes (PPROM) continues to be a major
      cause of preterm births. The objective of this study was to compare the morbidity
      of patients with PPROM nonvertex presentations with patients with PPROM with
      vertex presentations. STUDY DESIGN: A retrospective analysis of data from 74
      patients with PPROM with nonvertex presentations (study group) and 74 patients
      with PPROM with vertex presentations (control group) comprised the 2 study
      groups. All patients that met the study admission criteria were treated in a
      similar manner at 1 of 3 level-III hospitals. The gestational ages at delivery of
      all patients were between 23-34 weeks, and the gestational ages between case and
      control patients were matched for gestational age. RESULTS: A statistically
      significant (P = .03) higher incidence of a prolapsed umbilical cord was found in
      the study group (n = 8; 10.8%) relative to the control group (n = 1; 1.4%). More
      infants in the study group had low 5-minute Apgar scores (<5) and/or low cord pH
      (<7.20; n = 25 [33.8%]) than in the control group (n = 12 [16.2%]; P = .02). Five
      infants with breech presentations underwent a precipitous unplanned vaginal
      delivery. Significant morbidity was not detected in these 5 infants. CONCLUSION:
      After transfer to an antenatal ward, patients with PPROM with nonvertex
      presentations appear to have a significantly higher risk for prolapsed umbilical
      cords, lower Apgar scores, and/or lower umbilical cord blood pH values, when
      compared with their vertex counterparts. Additionally, there appears to be
      substantial risk of an unintended, vaginal breech delivery.

PMID- 17547898
TI  - Endometrial cells identified in cervical cytology in women > or = 40 years of
      age: criteria for appropriate endometrial evaluation.
AB  - OBJECTIVE: No consensus exists regarding evaluation of asymptomatic premenopausal
      women with benign endometrial cells (BECs) identified on cervical cytology. We
      determined the frequency of uterine pathology in asymptomatic women, > or = 40
      years of age, positive for BECs on cervical cytology. STUDY DESIGN: Cervical
      cytopathology records from a Midwestern US teaching hospital from April 2002
      through December 2005 were reviewed and cases with BECs identified. Patient age,
      symptomatology, and endometrial sampling results were obtained. RESULTS: Of
      194,717 records examined, 1784 (0.9%) of women > or = 40 years had BECs present
      and 440 had follow-up endometrial pathology. There were 4 cases of complex
      hyperplasia with atypia, 2 from patients < or = 50 years, 1 was asymptomatic; 4
      cases of adenocarcinoma were identified, all from women > 50 years. CONCLUSION:
      To date, the present study is among the largest follow-up studies of women with
      BECs on cervical cytology. Follow-up endometrial sampling may not be indicated in
      asymptomatic patients < or = 50 years.

PMID- 17547899
TI  - The ultrasound estimation of amniotic fluid volume in diamniotic twin pregnancies
      and prediction of peripartum outcomes.
AB  - OBJECTIVE: To determine ultrasonic estimations of amniotic fluid in diamniotic
      twins across gestation using the single deepest pocket (SDP) technique and
      correlate volumes to intrapartum and neonatal outcomes. STUDY DESIGN: Prospective
      observational study using diamniotic dichorionic and diamniotic monochorionic
      pregnancies. Intrapartum and neonatal outcomes were evaluated. RESULTS: Between
      April 2004 and April 2006, 299 women were recruited. There was no significant
      relationship between SDP and gestational age. Statistically significant
      differences by SDP groups (for low, normal, and high volumes) include preterm
      delivery (P = .043; 56, 62, and 86%), abnormal labor tracing (P = .013; 5, 8, and
      27%), fetal labor intolerance (P = .026; 6, 9, and 27%), Apgar scores at 5
      minutes (P = .028; 17, 10, and 27%) and any neonatal complications (P = .002; 28,
      21, and 55%). CONCLUSION: The SDP is constant between 17 and 37 weeks. Fetal
      labor intolerance and adverse neonatal outcomes are greater in a twin with
      hydramnios.

PMID- 17547900
TI  - Early maturation of sinus rhythm dynamics in high-risk fetuses.
AB  - OBJECTIVE: The purpose of this study was to compare cardiac dynamics of high-risk
      and low-risk fetuses using beat to beat variability. STUDY DESIGN: This study
      obtained 214 fetal magnetocardiography recordings from a group of high-risk
      fetuses with maternal conditions associated with placental insufficiency with the
      risk of developing intrauterine growth restriction or were already diagnosed with
      intrauterine growth restriction. For purpose of comparison, another 136
      recordings were obtained from low-risk fetuses. The cardiac beat-to-beat
      intervals computed as RR intervals were analyzed from both groups using the mean
      and median interval, standard deviation of normal-to-normal intervals, root mean
      square of the successive differences, and the fraction of the normal-to-normal
      intervals (pNNx) that differ by more than the chosen tolerance level of 'x'
      milliseconds from the previous normal-to-normal intervals. Tests for significance
      between high-risk and low-risk fetuses were calculated using an independent
      samples t test within the following gestational age groups, 27-30 weeks, 31-35
      weeks, and 36-40 weeks. RESULTS: The root mean square of the successive
      differences, and the pNNx showed a significant difference between the low-risk
      and high-risk fetuses in the 31-35-week and the 36-40-week divisions. In the 31
      35-week age division, low-risk fetuses had significantly lower root mean square
      of the successive differences, and pNN values than the high risk, but in the 36
      40-week division, the low-risk fetuses had significantly higher root mean square
      of the successive differences, and pNN values. CONCLUSION: Cardiac dynamics for
      fetuses of mothers at risk for placental insufficiency mature quicker than
      fetuses not at risk for placental insufficiency.

PMID- 17547901
TI  - An episode of preterm labor is a risk factor for the birth of a small-for
      gestational-age neonate.
AB  - OBJECTIVE: Patients with an episode of preterm labor that subsides in response to
      tocolysis and who, subsequently, deliver at term are considered to have false
      preterm labor. However, the episode of "preterm labor" may represent the uterine
      response (ie, uterine contractions) to an insult not severe enough to trigger
      preterm parturition, but which may put the fetus at risk for additional pregnancy
      complications, including growth restriction. The objective of this study was to
      compare the frequency of small-for-gestational-age (SGA) neonates among patients
      with an episode of increased uterine contractility who delivered at term and
      those who delivered preterm. STUDY DESIGN: This retrospective cohort study
      included 849 patients. Inclusion criteria were (1) regular uterine contractions
      that required hospitalization, (2) intact membranes, and (3) gestational age
      between 20 and 36 weeks. SGA was defined as a birth weight of <10th percentile
      for gestational age. Placental pathologic evidence was reviewed, and the results
      were used to classify patients into an inflammatory cluster, vascular cluster, or
      both. Contingency tables, Mann-Whitney U test, and multivariate logistic
      regression were used for statistical analyses. A probability value of <.05 was
      considered significant. RESULTS: The prevalence of SGA neonates in the study
      population was 16.1% (124/772). Patients who delivered at term had a
      significantly higher frequency of SGA neonates than those who delivered preterm
      (21.5% [64/298] vs 12.7% [60/474]; P = .001); the results of placental pathologic
      evidence were available in 63.7% (492/772) of the patients. Patients who
      delivered at term had a higher frequency of fetal or maternal vascular lesions
      without histologic evidence of inflammation than those who delivered preterm
      (29.1 % [43/148] vs 18.9% [65/344]; P = .01). Term delivery after an episode of
      regular preterm uterine contractions was associated with an odds ratio of 2.22
      (95% CI, 1.28-3.85) to deliver an SGA neonate after the statistics were
      controlled for confounding variables. A subanalysis limited to patients who
      received tocolysis showed similar results. CONCLUSION: Patients with an episode
      of increased uterine contractility that subsided and who deliver at term are at
      risk for delivering an SGA neonate, which suggests that an episode of false
      preterm labor is not a benign condition. We propose that insults to the
      fetoplacental unit may be resolved by either irreversible preterm parturition or
      restriction of fetal growth.

PMID- 17547902
TI  - Recurrence risk for preterm delivery.
AB  - OBJECTIVE: To estimate recurrence risk of preterm delivery in third births. STUDY
      DESIGN: We conducted a population-based cohort study of Missouri mothers who
      delivered 3 consecutive singleton live births during 1989-1997. The recurrence
      risk was computed for 4 cohorts based on prior preterm delivery status and
      adjusted using Mantel-Haenszel stratified analysis. RESULTS: The study population
      included 19,025 third births. The recurrence risk ranged from 42% (for women with
      2 prior preterm deliveries), through 21% (term/preterm) and 13% (preterm/term),
      to 5% (term/term). The recurrence risk was highest (57%) for women with 2 prior
      very preterm deliveries (21-31 weeks) and lowest (33%) for those with 2 prior
      moderate preterm deliveries (32-36 weeks). The recurrence risk was less
      pronounced for women with 1 prior very or moderate preterm delivery. CONCLUSION:
      These data show a strong association between prior preterm delivery and
      recurrence risk, which is affected by the frequency, order, and severity of prior
      preterm births.

PMID- 17547903
TI  - Reproductive medicine: where we have been, where we are, where are we going? An
      ethical perspective.

PMID- 17547904
TI  - Asymptomatic bacteriuria and intimate partner violence in pregnant women.
AB  - OBJECTIVE: This study was undertaken to determine whether the association of
      intimate partner violence with urinary tract infection and pyelonephritis in
      pregnancy is due to a higher rate of asymptomatic bacteriuria in those suffering
      intimate partner violence. STUDY DESIGN: Women enrolling in prenatal care had
      urine collected for quantitative culture (n = 342) and completed 2 scales with a
      computer-based survey system: The Conflict Tactics Scale for verbal and physical
      abuse and the Castro survey for sexual abuse. RESULTS: The prevalence of verbal
      abuse during pregnancy was 46.9%, physical abuse, 7.6%, sexual abuse 5.8%. No
      significant associations were seen between quantitative culture of uropathogens
      and verbal, physical, or sexual abuse. CONCLUSION: It is unlikely that the reason
      for the association of urinary tract infection and intimate partner violence is
      due to a higher number of uropathogens present in the urine of women with verbal,
      physical, or sexual abuse.

PMID- 17547905
TI  - Perinatal outcomes after successful and failed trials of labor after cesarean
      delivery.
AB  - OBJECTIVE: To compare maternal and neonatal outcomes after successful and failed
      trials of labor after cesarean in women at term, excluding uterine ruptures, and
      to examine predictors of successful and failed trials of labor. STUDY DESIGN:
      Matched maternal and neonatal data from 1993-1999 in women with singleton term
      pregnancies with prior cesarean undergoing trial of labor were reviewed. Women
      with uterine rupture were excluded. Maternal and neonatal outcomes were analyzed
      for successful and failed trials. Predictors of success and failure were
      examined. RESULTS: 1284 women and their neonates were available for analysis.
      1094 (85.2%) had a vaginal birth and 190 (14.8%) underwent repeat cesarean.
      Failed trials of labor were associated with higher incidence of choriamnionitis
      (25.8% vs. 5.5%, P<.001), postpartum hemorrhage (35.8% vs. 15.8%, P<.001),
      hysterectomy (1% vs. 0%, P=.022), neonatal jaundice (17.4% vs.10.2%, P=.004) and
      composite major neonatal morbidities (6.3% vs. 2.8%, P=.014). CONCLUSION: Failed
      trial of labor in women at term with prior cesarean is associated with increased
      maternal and neonatal morbidities.

PMID- 17547906
TI  - Duration of the second stage of labor in multiparous women: maternal and neonatal
      outcomes.
AB  - OBJECTIVE: This study was undertaken to examine perinatal outcomes associated
      with the second stage of labor in multiparous women. STUDY DESIGN: This is a
      retrospective cohort study of all term, cephalic, singleton births delivered by
      multiparous women between 1991 and 2001. Duration of the second stage of labor
      was stratified into hourly intervals: 0-1 hour, 1-2 hours, 2-3 hours, and 3 hours
      or longer. Perinatal outcomes were analyzed by using chi2 test and multivariable
      logistic regression models, by using P<.05 and 95% CI to indicate statistical
      significance. RESULTS: Compared with women who delivered between the 0- and 2
      hour interval, women with a second stage more than 3 hours had higher risks of
      operative vaginal deliveries (odds ratio = 13.27; 95% CI [9.38-18.8]), cesarean
      deliveries (odds ratio = 6.00; [4.06-8.86]), and maternal morbidity including
      third- or fourth-degree perineal lacerations, postpartum hemorrhage, and
      chorioamnionitis. Their neonates had higher risks of 5-minute Apgar score less
      than 7 (odds ratio = 3.63; 95% CI [1.77-7.43]), meconium stained amniotic fluid
      (odds ratio = 1.44; 95% CI [1.07-1.94]), admission to intensive care nursery
      (odds ratio = 2.08; 95% CI [1.15-3.77]), composite neonatal morbidity (odds ratio
      = 1.85; 95% CI [1.23-2.77]), and longer neonatal stay in the hospital (odds ratio
      = 1.67; 95% CI [1.11-2.51]). CONCLUSION: Multiparous women with a second stage of
      3 hours or greater are at increased risks for operative deliveries, peripartum
      morbidity, and undesirable neonatal outcomes. These outcomes should be considered
      in the management of multiparous women with a second stage of labor beyond 3
      hours.

PMID- 17547907
TI  - Disruptive behavior in obstetrics: a hidden threat to patient safety.
AB  - OBJECTIVE: This study was to determine the frequency of disruptive behavior on
      labor and delivery units, its effect on work performance, and its contribution to
      adverse outcomes. STUDY DESIGN: One hundred questionnaires were sent to nurse
      managers of labor and delivery units in selected hospitals in Washington, Oregon,
      and California regarding the occurrence of disruptive behavior and the
      consequences of this behavior with respect to patient safety. RESULTS: Fifty-six
      percent of questionnaires were returned. Disruptive behavior was currently
      occurring on 60.7% of the units. Multiple professionals demonstrated the
      behavior. Nurses had left the unit and there were reported adverse outcomes as a
      consequence of this behavior. CONCLUSION: Disruptive behavior occurs frequently
      on labor and delivery units on the West Coast. This behavior contributed to the
      nursing shortage, near misses, and adverse occurrences, and was exhibited by a
      broad range of professionals. The behavior was not always effectively managed by
      the organization.

PMID- 17547908
TI  - Predictors of hysterectomy after uterine artery embolization for leiomyoma.
AB  - OBJECTIVE: This study was undertaken to describe long-term outcomes after uterine
      artery embolization for leiomyoma. STUDY DESIGN: Data from Kaiser Permanente
      Northern California members undergoing uterine artery embolization for leiomyoma
      before July 2001 were collected. Survival analysis was performed to describe
      hysterectomy rates and identify predictors of hysterectomy. RESULTS: Uterine
      artery embolization was performed in 562 women from 1997-2001. Thirty-three women
      (5.9%) had unilateral uterine artery embolization. One hundred women (18%)
      underwent hysterectomy after uterine artery embolization, and 32 (5.7%) had
      additional uterine sparing procedures. Only unilateral uterine artery
      embolization predicted subsequent hysterectomy (relative risk = 2.19; 95% CI 1.34
      3.57), whereas age, indication, uterine volume, embolizing particle, and
      radiologist experience did not. The rate of hysterectomy at 5 years was 19.7%;
      rates for bilateral and unilateral uterine artery embolizations were 18.5% and
      39.2%, respectively. Fifty-four women (9.6%) had emergency room visits and 17
      (3%) had unplanned readmissions. CONCLUSIONS: Uterine artery embolization for
      leiomyoma permits uterine conservation in more than 80% of women monitored long
      term. When bilateral procedures cannot be performed, failure rates are
      considerably higher.

PMID- 17547909
TI  - Chorionic villus sampling and risk for hypertensive disorders of pregnancy.
AB  - OBJECTIVE: This study was undertaken to evaluate the relationship between
      chorionic villus sampling at 10-13 weeks' gestational age and hypertensive
      disorders of pregnancy. STUDY DESIGN: The prevalence of hypertensive disorders of
      pregnancy in women with singleton gestations, undergoing transcervical or
      transabdominal chorionic villus sampling between 10 weeks 0 days' and 13 weeks 6
      days' gestational age was compared with that of control women with singleton
      gestations having first-trimester screening with nuchal translucency and
      biochemistry between 11 weeks 0 days' and 13 weeks 6 days' gestational age.
      Patients having invasive prenatal diagnosis (chorionic villus sampling or
      amniocentesis) were excluded from the control group. All patients delivered at
      Cedars-Sinai Medical Center. RESULTS: There were 1540 women who had chorionic
      villus sampling and 840 controls. Hypertensive disorders of pregnancy were
      diagnosed in 76 (4.9%) patients in the chorionic villus sampling group and in 37
      (4.4%) of the controls (chi2 = 0.34, P = .31). CONCLUSION: Chorionic villus
      sampling at 10 to 13 weeks' gestational age does not appear to increase the
      overall risk for hypertensive disorders of pregnancy. However, there appears to
      be an association between chorionic villus sampling and severe hypertensive
      disorders including severe preeclampsia, eclampsia, and hemolysis, elevated liver
      enzymes, and low platelet count syndrome.

PMID- 17547910
TI  - Night sweats, sleep disturbance, and depression associated with diminished libido
      in late menopausal transition and early postmenopause: baseline data from the
      Herbal Alternatives for Menopause Trial (HALT).
AB  - OBJECTIVE: The objective of the study was to evaluate the association of
      depression, sleep disturbance, and menopausal symptoms with diminished libido.
      STUDY DESIGN: Data from a 2001-2002 baseline survey of 341 peri- and
      postmenopausal women, aged 45-55 years, participating in a randomized trial, was
      analyzed. Eligibility included at least 2 hot flashes and/or night sweats per day
      and no hormone therapy for at least the prior 3 months. The survey evaluated
      sexual function, depression, sleep, and vasomotor symptoms. We examined the
      association between these factors, using multivariate regression models. RESULTS:
      Of 341 women, 64% had diminished libido, 18% had moderate to severe depression,
      and 43% had poor sleep quality. Women averaged 4.6 hot flashes and 1.9 night
      sweats per day. Depressive symptoms (P = .003), poor sleep (P = .02), and night
      sweats (P = .04) were significantly associated with diminished libido.
      CONCLUSION: Factors associated with diminished libido in midlife are complex but
      include depression, disturbed sleep, and night sweats, all common symptoms of the
      menopausal transition and early menopause.

PMID- 17547911
TI  - Isolated choroid plexus cyst or echogenic cardiac focus on prenatal ultrasound:
      is genetic amniocentesis indicated?
AB  - OBJECTIVE: The purpose of this study was to determine whether or not genetic
      amniocentesis is warranted when isolated choroid plexus cysts (CPC) or echogenic
      cardiac foci (EF) are noted on prenatal ultrasound. STUDY DESIGN: We performed a
      retrospective analysis on patients from our perinatal database. All obstetric
      patients with CPC or EF noted on second-trimester perinatology ultrasound from
      April, 1998 to November, 2004 were included. Information regarding ultrasound
      findings and neonatal outcome were analyzed. RESULTS: During the study period,
      515 patients with CPC or EF were evaluated. Of these, 429 (83.3%) had isolated
      CPC or EF and 86 (16.7%) had additional risk factors. The incidence of abnormal
      karyotype was 0 versus 2.3%, respectively (P = .03). The additional risk factors
      considered were: advanced maternal age, abnormal serum triple marker screening,
      and/or other abnormal ultrasound findings. Furthermore, during the study period
      there were 20,122 live births and 27 (0.1%) cases of aneuploidy diagnosed
      postnatally. Of these, none had isolated CPC or EF on prenatal ultrasound.
      CONCLUSION: CPC or EF noted on prenatal ultrasound warrants referral for careful
      consultative ultrasound evaluation. In the absence of other risk factors,
      however, genetic amniocentesis for isolated CPC or EF does not appear to be
      necessary.

PMID- 17547912
TI  - Effects on perinatal outcome of treating women with 1 elevated glucose tolerance
      test value.
AB  - OBJECTIVE: This study was undertaken to determine whether medical nutrition
      therapy and home glucose monitoring can reduce complications in pregnancies with
      1 elevated oral glucose tolerance test value. STUDY DESIGN: This was a
      retrospective case-control study with historical controls. Medical records of
      women with one elevated oral glucose tolerance test value between January 2001
      and June 2006 were reviewed; routine medical nutrition therapy and self-blood
      glucose monitoring for this group of women was initiated in April 2004. Women
      before (untreated group) and after (treated group) the initiation of therapy were
      compared. Baseline characteristics, as well pregnancy weight gain, birthweight
      greater than 4000 g, incidence of shoulder dystocia, cesarean delivery rate, and
      neonatal metabolic complications were compared. Student t test, Mann-Whitney U
      test, and chi2 test were used as appropriate, with P < .05 considered
      significant. RESULTS: Fifty-seven women comprised the untreated group, and 69
      were in the treated group. Except for greater prepregnancy weight in the treated
      group, maternal characteristics did not differ significantly between the 2
      groups. Mean birthweight was similar between untreated and treated subjects (3385
      g vs 3476 g, P = .45). Number of subjects with birthweights greater than 4000 g,
      shoulder dystocia, and unplanned cesarean deliveries were similar between the 2
      groups. CONCLUSION: In our patient population, women with 1 elevated oral glucose
      tolerance test value did not benefit from a structured program of medical
      nutritional therapy and self-blood glucose monitoring.

PMID- 17547913
TI  - Documented short-term continuation rates for combined hormonal contraceptives in
      an indigent population with ready access to contraceptive supplies.
AB  - OBJECTIVE: One problem women have successfully using combined hormonal
      contraception is the limited supplies they are dispensed. Patients at the Women's
      Health Care Clinic at the Los Angeles Biomedical Research Institute at Harbor
      UCLA Medical Center have virtually no barriers to method switching, so it is
      possible to estimate the impacts that more generous prescribing policies have on
      short-term continuation rates. STUDY DESIGN: Anonymous chart review of all women
      who initiated hormonal contraception between Jan. 1 and June 30, 2005. RESULTS:
      Only 40.4% of women had documented use for at least 3 months. Women dispensed
      supplies for 3 or more cycles at the initial visit were more likely to continue
      use for 3 months (47.8%) than were women dispensed fewer cycles (31.9%) (P <
      .0001). CONCLUSION: More liberal dispensing policies may increase the wastage of
      combined hormonal contraceptive product, but they significantly increase at least
      intermediate term use of those methods.

PMID- 17547914
TI  - Changes in rates of hysterectomy and uterine conserving procedures for treatment
      of uterine leiomyoma.
AB  - OBJECTIVE: The purpose of this study was to investigate treatment of uterine
      leiomyoma by hysterectomy and uterine conserving procedures (UCPs). STUDY DESIGN:
      Data from Kaiser Permanente Northern California members undergoing hysterectomy,
      myomectomy, uterine artery embolization (UAE) and endometrial ablation (EA) for
      uterine leiomyoma from 1997-2003 were collected. Statistical analysis included
      trend tests and survival analysis. RESULTS: Hysterectomy rates for leiomyoma
      decreased significantly from 2.13 per 1000 to 1.91 (P < .0001). Rates for
      myomectomy (.4-.37) and EA (.26-.27) remained stable (P = .17 and .26,
      respectively), whereas rates for UAE increased significantly from < .01-.24 (P <
      .0001). The combined rates for hysterectomy and UCPs remained stable at 2.79 (P =
      .95). Rate of hysterectomy after UCP increased over time, and at 6 years reached
      11.5%, 17.7%, and 7.9% for EA, UAE, and myomectomy, respectively. CONCLUSION:
      Whereas rate of hysterectomy for leiomyoma decreased, total rate of invasive
      treatment remained stable. Increase in rate of UAE had the greatest impact on
      treatment, possibly replacing hysterectomy.

PMID- 17547915
TI  - Faculty attrition in obstetrics and gynecology.
AB  - OBJECTIVE: The purpose of this study was to explore why
      obstetrician/gynecologists leave academic practice. STUDY DESIGN: From a sample
      of 5000 ACOG fellows, we identified obstetrician/gynecologists in faculty
      positions and those who had left academic practice. These groups were sent a
      survey to explore aspects of job satisfaction. Relationships between variables
      were tested using chi2 analyses. Means were computed for each subscale and
      differences between current and past faculty were tested with a multivariate
      analysis of variance model. RESULTS: There was a 65% response rate to the job
      satisfaction survey for a total of 280 current faculty and 146 previous faculty.
      There was no difference between the groups in job satisfaction. Faculty rated
      opportunities for teaching and administration more important as components of job
      satisfaction. Practitioners who left academics were more likely to be previous
      junior faculty and generalists. CONCLUSION: Junior faculty and generalists are
      more likely to leave academic practice than senior faculty and subspecialists.

PMID- 17547916
TI  - First-trimester combined screening: experience with an instant results approach.
AB  - OBJECTIVE: This study was undertaken to assess an instant results protocol for
      first-trimester combined screening. STUDY DESIGN: Retrospective analysis of
      patients having first-trimester combined screening between Nov. 1, 2003 and Oct.
      31, 2005. We evaluated the feasibility of patient self-collection and mail-in of
      blood samples before nuchal translucency ultrasound. Primary outcome was success
      with providing in-office, immediate screening results after the ultrasound.
      Predictor variables included age, ethnicity, insurance, and provider. The chi2
      analysis was performed. RESULTS: Two thousand three hundred ten women completed
      first-trimester combined screening, and 60.6% received instant results. When the
      biochemistry sample was collected at home, 80% received instant results. Age 35
      years or older predicted instant results (P = .001), whereas ethnicity,
      insurance, and referring provider did not. Comparing the prior 24 months, clinic
      volume increased by 18%. Diagnostic procedure volume was unchanged, although
      chorionic villus sampling increased by 12% (P = .02) and amniocentesis decreased
      by 6% (P = .049). CONCLUSION: Patients were able to obtain instant results in
      60.6% of cases, which appeared to increase the use of chorionic villus sampling.

PMID- 17547917
TI  - Miscarriage risk from amniocentesis performed for abnormal maternal serum
      screening.
AB  - OBJECTIVE: The purpose of this study was to evaluate miscarriage after mid
      trimester amniocentesis for abnormal maternal serum screening. STUDY DESIGN: An
      analysis of summary data from the California State maternal serum screening
      program on 32,050 women with an abnormal serum screen, a singleton fetus, and
      normal ultrasound was performed. Miscarriage before 24 weeks, days until
      miscarriage, gestational age at miscarriage, and maternal factors were compared.
      The power of this study could detect a 50% increase in miscarriage. RESULTS: The
      miscarriage rate with amniocentesis, 0.46% (69/15,005), was no different than
      without, 0.53% (90/17,045), P = .38. There was no difference in maternal age,
      serum biochemical factors, gestational age at miscarriage (21.1 weeks for both
      groups), or days until miscarriage (23 after amniocentesis and 20.4 without). Log
      rank test revealed no difference for gestational age at miscarriage (P = .61) or
      number of days until miscarriage (P = .40). CONCLUSION: The rate and timing of
      miscarriage was similar with or without amniocentesis in California women with
      abnormal maternal serum screening.

PMID- 17547919
TI  - Laparoscopic gonadectomy for androgen insensitivity syndrome: karyotype tells the
      tale.

PMID- 17547920
TI  - Reprint of "Fluorescence emission from PAMAM and PPI dendrimers [J. Colloid
      Interface Sci. 306 (2007) 222-227].
AB  - A strong fluorescence emission from poly(amido amine) (PAMAM) dendrimers with
      different terminal groups or a poly(propylene imine) (PPI) dendrimer was studied
      under different conditions by varying experimental parameters such as pH value,
      aging time, temperature, and concentration. The increase of fluorescence
      intensity was fast at low pH or high temperature but linear with respect to
      dendrimer concentration. It was reasonable that the formation of a fluorescence
      emitting moiety had a close relation to protonated tertiary amine groups in PAMAM
      or PPI dendrimers. Furthermore, oxidation of the tertiary amines was confirmed to
      play an important role, which was evidently caused by oxygen in air. The results
      of fluorescence decay indicated that the deactivation of luminescence was raised
      with increasing temperature. Dendrimers emitted blue photoluminescence along
      fiber chain templates on a fluorescent microscope.

PMID- 17547921
TI  - Formation and destruction of hydrogen bonds in gels and in aqueous solutions of N
      isopropylacrylamide and sodium acrylate observed by ATR-FTIR spectroscopy.
AB  - In this paper, the formation and destruction of hydrogen bonds in gels and in
      aqueous solutions of N-isopropylacrylamide (NIPA) and sodium acrylate (SA) were
      studied using Fourier transform infrared (FTIR) spectroscopy with attenuated
      total reflection (ATR). Aqueous solutions of NIPA and SA monomers with different
      pHs were prepared, and the ATR-FTIR spectra were obtained immediately after
      preparing the solution and after having been stored at room temperature for 6
      months. It was found that the IR spectra evidently changed after 6 months due to
      polymerization, and the viscosity of a solution in the lowest pH system increased
      with time and finally the solution became a gel. The detailed analysis of the IR
      spectra indicated that the network of the gel was formed by the formation of
      hydrogen bonds (without crosslinker). Moreover, this physical gel exhibited the
      re-swelling transition by increasing the pH of solvent. The transition was caused
      by the destruction of hydrogen bonds due to the dissociation of carboxyl groups,
      which was also confirmed by the IR spectroscopy.

PMID- 17547922
TI  - Soluble complexes in aqueous mixtures of low charge density comb polyelectrolyte
      and oppositely charged surfactant probed by scattering and NMR.
AB  - A low charge density polyelectrolyte with a high graft density of 45 units long
      poly(ethylene oxide) side-chains has been synthesized. In this comb polymer,
      denoted PEO(45)MEMA:METAC-2, 2 mol% of the repeating methacrylate units in the
      polymer backbone carry a permanent positive charge and the remaining 98 mol% a 45
      unit long PEO side-chain. Here we describe the solution conformation of this
      polymer and its association with an anionic surfactant, sodium dodecylsulfate,
      SDS. It will be shown that the polymer can be viewed as a stiff rod with a cross
      section radius of gyration of 29 A. The cross section of the rod contracts with
      increasing temperature due to decreased solvency of the PEO side-chains. The
      anionic surfactant associates to a significant degree with PEO(45)MEMA:METAC-2 to
      form soluble complexes at all stoichiometries. A cooperative association is
      observed as the free SDS concentration approaches 7 mM. At saturation the number
      of SDS molecules associated with the polymer amounts to 10 for each PEO side
      chain. Two distinct populations of associated surfactants are observed, one is
      suggested to be molecularly distributed over the comb polymer and the other
      constitutes small micellar-like structures at the periphery of the aggregate.
      These conclusions are reached based on results from small-angle neutron
      scattering, static light scattering, NMR, and surface tension measurements.

PMID- 17547923
TI  - Synthesis of highly-ordered mesoporous silica particles using mixed cationic and
      anionic surfactants as templates.
AB  - We applied a molecular assembly formed in an aqueous surfactant mixture of
      cationic cetyltrimethylammonium bromide (CTAB) and anionic sodium octylsulfate
      (SOS) as templates of mesoporous silica materials. The hexagonal pore size can be
      controlled between 3.22 and 3.66 nm with the mixed surfactant system. In
      addition, we could observe the lamellar structure of the mixed surfactants with
      precursor molecules, which strongly shows the possibility of precise control of
      both the pore size and the structure of pores by changing the mixing ratio of
      surfactants. Moreover, use of the cationic surfactant having longer hydrophobic
      chain like stearyltrimethylammonium bromide (STAB) caused the increase in d(100)
      space and shifted the point of phase transition from hexagonal phase to lamellar
      phase to lower concentration of SOS.

PMID- 17547924
TI  - Electrostatic effects in films stabilised by non-ionic surfactants.
AB  - The disjoining pressure Pi of films of aqueous octyl-beta-glucoside (beta
      C(8)G(1)) solutions with and without salt was measured as a function of the film
      thickness by means of a thin film pressure balance. The analysis of the
      experiments confirms the presence of an electrostatic double layer which
      dominates the long-range interactions as found in previous experiments with other
      non-ionic surfactants in the presence of added salt. In the absence of salt, we
      find a local ion concentration much higher than that of the residual ionic
      impurities present in the bulk solution.

PMID- 17547925
TI  - Reprint of "Self-diffusion study of micelles in poly(oxyethylene)
      polydimethylsiloxane diblock copolymer and poly(oxyethylene) alkyl ether systems"
      [J. Colloid Interface Sci. 300 (2006) 354-360].
AB  - Self-diffusion constants of amphiphilic molecules in D(2)O solutions of mixed
      poly(oxyethylene)-polydimethylsiloxane diblock copolymer (POE-PDMS,
      Si(m)C(3)EO(n)) and poly(oxyethylene) dodecyl ether (C(12)EO(n)) were measured by
      pulsed-field-gradient NMR method. In the D(2)O/Si(25)C(3)EO(51.6)/C(12)EO(8) or
      D(2)O/Si(52)C(3)EO(51.6)/C(12)EO(8) systems, small and large micelles coexist in
      a wide range of Si(m)C(3)EO(51.6) fraction in total amphiphiles, whereas such a
      coexisting phenomenon does not take place in the
      D(2)O/Si(5.8)C(3)EO(51.6)/C(12)EO(8) system. The coexisting phenomenon also takes
      place in the D(2)O/Si(25)C(3)EO(51.6)/C(12)EO(5) system although the range of
      mixing fraction is limited. By obtaining each contribution of surfactant and
      copolymer molecules to the attenuation decay of the echo signal from the proton
      of the poly(oxyethylene) chain, we could evaluate the composition of the mixed
      micelles in the D(2)O/Si(25)C(3)EO(51.6)/C(12)EO(8) system. The copolymer content
      in the mixed micelle increases proportionally to the copolymer mole fraction in
      the aqueous solution. From the series of self-diffusion measurements, we can
      conclude that the miscibility of Si(m)C(3)EO(n) and C(12)EO(n) in aqueous
      micelles becomes poor and the coexisting phenomenon takes place when the PDMS
      chain becomes much longer than the dodecyl chain of C(12)EO(n) or the POE chain
      of C(12)EO(n) becomes long. Furthermore it is also revealed that very few
      silicone copolymer molecules can be incorporated in small surfactant micelles.

PMID- 17547926
TI  - An attempt to detect bicontinuity from SANS data.
AB  - SANS is a powerful tool to characterise microemulsions, which can have a
      discontinuous droplet-like structure (oil in water (O/W), water in oil (W/O)) or
      a bicontinuous one. In the present study, we try to distinguish O/W, W/O and
      bicontinuous microemulsions by SANS measurements under practical conditions and
      by a certain evaluation technique. For this reason we chose the well
      characterised ternary system water-non-ionic surfactant (C(12)E(5))-oil (n
      octane), at a fixed surfactant concentration and performed SANS measurements
      throughout its one-phase channel where droplet-like phases as well as
      bicontinuous phases are well established. We evaluated the scattering data via
      the 'Generalised Indirect Fourier Transformation' method (GIFT) which is based on
      a particulate picture. It should therefore give good results in the droplet
      domains while a poor fit could be expected for the bicontinuous regime. For
      comparison we also applied the model of Teubner and Strey (TS) which was
      developed especially for bicontinuous phases, here a bad fit can be expected for
      the particulate regime. The data evaluation via GIFT leads to relatively good
      fits throughout the one-phase channel. The results are physically meaningful and
      are comparable to those of the TS model. We show that the scattering pattern of a
      bicontinuous microemulsion can be represented by that of a polydisperse
      particulate system. This is in clear contradiction to the expectation that the
      particle picture used in the GIFT method must fail when the bicontinuous regime
      is reached.

PMID- 17547927
TI  - Generation of metal oxide nanoparticles in optimised microemulsions.
AB  - The phase behavior and structure of aqueous-in-n-heptane microemulsions,
      stabilized by surfactant mixtures of di-n-didodecyldimethylammonium bromide,
      DDAB, and Brij(R)35 were studied by small angle (neutron or X-ray) scattering
      techniques. The aqueous nanodroplets contain either a precursor reactive salt or
      a precipitating agent, so that simple mixing induces nanoparticle formation.
      These formulated microemulsions display good phase stability against added polar
      additives such as monovalent, divalent, trivalent metal ions, ammonia solution,
      tetrabutylammonium hydroxide, and their mixtures. Nanoparticle formation was
      demonstrated via precipitation of metal oxides inside the water nanodroplets,
      affording control over the resulting particle size. Nanoparticle characteristic
      size (XRD- and HR-TEM derived sizes) and specific surface areas (S(BET) (m(2)g(
      1))) for iron oxide and CeO(2) prepared in these mixed microemulsions, are
      compared with those stabilized by single surfactants DDAB and Pure AOT.

PMID- 17547928
TI  - Coexisting lamellar phases in water-oil-surfactant systems induced by the
      addition of an amphiphilic block copolymer.
AB  - We report here a pioneering study using quadrupolar splitting NMR to detect new
      phases and phase compositions in the quasi-ternary microemulsion system water
      decane-C(10)E(4)/PEP5-PEO5. The striking observation is that at certain
      compositions the polymer is apparently no longer incorporated into the membranes
      of the lamellar phase due to space restrictions. The polymer therefore induces a
      phase separation into two different lamellar phases L(alpha)(1) and L(alpha)(2)
      such that it fits into L(alpha)(1) while the excess surfactant forms a polymer
      free L(alpha)(2) phase.

PMID- 17547929
TI  - DNA encapsulation by biocompatible catanionic vesicles.
AB  - The encapsulation of DNA by catanionic vesicles has been investigated; the
      vesicles are composed of one cationic surfactant, in excess, and one anionic.
      Since cationic systems are often toxic, we introduced a novel divalent cationic
      amino-acid-based amphiphile, which may enhance transfection and appears to be
      nontoxic, in our catanionic vesicle mixtures. The cationic amphiphile is arginine
      N-lauroyl amide dihydrochloride (ALA), while the anionic one is sodium
      cetylsulfate (SCS). Vesicles formed spontaneously in aqueous mixtures of the two
      surfactants and were characterized with respect to internal structure and size by
      cryogenic transmission electron microscopy (cryo-TEM); the vesicles are markedly
      polydisperse. The results are compared with a study of an analogous system based
      on a short-chained anionic surfactant, sodium octylsulfate (SOS). Addition of DNA
      to catanionic vesicles resulted in associative phase separation at very low DNA
      concentrations; there is a separation into a precipitate and a supernatant
      solution; the latter is first bluish but becomes clearer as more DNA is added.
      From studies using cryo-TEM and small angle X-ray scattering (SAXS) it is
      demonstrated that there is a lamellar structure with DNA arranged between the
      amphiphile bilayers. Comparing the SOS containing DNA-vesicle complexes with the
      SCS ones, an increase in the repeat distance is perceived for SCS. Regarding the
      phase-separating DNA-amphiphile particles, cryo-TEM demonstrates a large and
      nonmonotonic variation of particle size as the DNA-amphiphile ratio is varied,
      with the largest particles obtained in the vicinity of overall charge neutrality.
      No major differences in phase behavior were noticed for the systems here
      presented as compared with those based on classical cationic surfactants.
      However, the prospect of using these systems in real biological applications
      offers a great advantage.

PMID- 17547930
TI  - The EACN scale for oil classification revisited thanks to fish diagrams.
AB  - The phase behavior of C(10)E(4)-oil-water systems at constant o/w ratio and
      variable temperature (fish diagram) has been investigated for several homologous
      oil families. The temperature T( *) and surfactant concentration C( *) at the
      critical point were determined for 10 n-alkanes varying from C(6) to C(28) as
      well as for a series of alkylcyclohexanes and alkylbenzenes. On the basis of T(
      *), equivalent alkane carbon numbers (EACN) were assigned to nonlinear alkanes,
      alkylbenzenes, and alkylcyclohexanes. The consistency of the method was shown by
      corroborating that the EACN values of oils previously investigated with other
      C(i)E(j) (dibutyl ether, squalane, isopropyl myristate, and dodecylbenzene) are
      the same when determined with C(10)E(4). The fact that two oils of different
      nature but with the same EACN (i.e., the same T( *)) do not exhibit the same C(
      *) is discussed in terms of monomeric solubility of the surfactant in the oil
      (CMC(oil)).

PMID- 17547931
TI  - Unusual formation of small aggregates by mixing giant multilamellar vesicles.
AB  - The phase behavior and structure of aggregates in a hydrophobic block copolymer
      (L121)/double-tailed surfactant (AOT)/water system have been studied by phase
      study, fluorescence spectrometry, dynamic light scattering, transmission electron
      microscopy, small angle X-ray scattering (SAXS) and conductivity measurements. An
      isotropic, one-phase region is found between two biphasic regions containing
      large vesicles, namely, transparent samples are formed by mixing two turbid
      solutions. Depending on the AOT/L121 ratio, the isotropic region can be quite
      stable against temperature. The phase transition between the two regions can be
      detected by the used techniques, and structural transitions in the aggregates are
      inferred. The experimental evidence indicates that mixed aggregates are formed at
      very low concentrations, much lower than the critical micellar concentration of
      AOT. These micelle-like aggregates contain a mixed hydrophobic core, are small (2
      4 nm), and seem to be quasi-spherical, which is an unexpected result since the
      packing parameters of the single amphiphiles do not favor such small quasi
      spherical shapes. This behavior might have interesting implications in the
      release of substances from vesicles when their structure is disrupted.

PMID- 17547932
TI  - Triacylglycerol microemulsions stabilized by alkyl ethoxylate surfactants--a
      basic study. Phase behavior, interfacial tension and microstructure.
AB  - As triacylglycerols are the main components of natural fats and oils their
      solubilization in the form of emulsions or microemulsions was of great interest
      within the last years. However, systematic studies of their properties along the
      classical lines of complex fluids science are still missing. In the present paper
      we focus on the phase behavior, the interfacial tension and the microstructure of
      systems of type H(2)O/NaCl-triacylglycerol-alkylpolyglycolether (C(i)E(j)). The
      interfacial tension between water and oil sigma(ab) is high in a microemulsion
      system containing triolein. Thus, one needs high surfactant mass fractions to
      formulate a single-phase microemulsion. We show that this is not only true for
      triolein, but also for saturated long-chained triacylglycerols. The determination
      of the amphiphilicity factor f(a) and the calculation of the bending rigidities
      of the amphiphilic film confirm that despite the fact that high surfactant mass
      fractions and high temperatures are needed to solubilize triolein in a system of
      type H(2)O/NaCl-triacylglycerol-alkylpolyglycolether (C(i)E(j)), this is still a
      microemulsion in the narrower sense.

PMID- 17547933
TI  - Micelle structures in aqueous solutions of glucose-based surfactants having an
      isoprenoid-type hydrophobic chain.
AB  - Surfactant self-diffusion coefficients have been measured on a binary system of 1
      O-beta-3,7-dimethyloctyl-D-maltopyranoside (beta-Mal(2)(Ger))/water and a mixed
      surfactant system of beta-Mal(2)(Ger)/1-O-beta-3,7-dimethyloctyl-D
      glucopyranoside (beta-Glc(Ger))/water at 25 degrees C. For comparison,
      measurements have also been made on 1-O-beta-decyl-D-maltopyranoside (beta
      Mal(2)C(10))/water and beta-Mal(2)C(10)/1-O-beta-decyl-D-glucopyranoside (beta
      GlcC(10))/water. The hydrodynamic radius of beta-Mal(2)(Ger) micelles obtained
      from the micellar diffusion coefficient is around 3 nm and nearly equal to that
      of beta-GlcC(10) micelles within experimental error. In the mixed surfactant
      systems, the hydrodynamic radii for both systems increase with increasing X(G)
      (the mole fraction of beta-Glc(Ger) or beta-GlcC(10) in the total mixed solute)
      above X(G) congruent with 0.4 when the total surfactant concentration is kept
      constant at 2 wt%. The R(H) of beta-Glc(Ger)/Mal(2)(Ger) micelles increases more
      rapidly than beta-GlcC(10)/beta-Mal(2)C(10) micelles, and then phase separation
      occurs at X(G) congruent with 0.65. On the other hand, the R(H) of beta
      GlcC(10)/beta-Mal(2)C(10) micelles continues to increase until the phase
      separation occurs at X(G) congruent with 0.92. Measurements have also been
      performed as a function of total surfactant concentration at constant X(G)
      (=0.6). The CMC of the beta-Glc(Ger)/Mal(2)(Ger) system is larger than that of
      the beta-GlcC(10)/beta-Mal(2)C(10) system as expected from the results of the
      pure surfactant systems published previously. The R(H) increases with increasing
      total surfactant concentration for both systems. At higher concentrations, the
      R(H) of beta-Glc(Ger)/Mal(2)(Ger) micelles increases more rapidly than beta
      GlcC(10)/beta-Mal(2)C(10) micelles. These results can be explained by the fact
      that the geranyl and decyl chains have the same volume but different chain
      lengths.

PMID- 17547934
TI  - Phase and rheological behavior of the polymerizable surfactant CTAVB and water.
AB  - The phase and rheological behaviors of the polymerizable surfactant,
      cetyltrimethylammonium benzoate (CTAVB), and water as a function of surfactant
      concentration and temperature are investigated here. The critical micelle
      concentration (cmc) and the (cmc(2)), as well as the Krafft temperature (T(K)),
      are reported. A large highly viscous micellar solution region and hexagonal- and
      lamellar-phase regions were identified. The micellar solutions exhibit shear
      thickening in the dilute regime, below the overlapping or entanglement
      concentration. At higher concentrations, wormlike micelles form and the solutions
      show strong viscoelasticity and Maxwell behavior in the linear regime and shear
      banding flow in the nonlinear regime. The linear viscoelastic regime is analyzed
      with the Granek-Cates model, showing that the relaxation is controlled by the
      kinetics of reformation and scission of the micelles. The steady and unsteady
      responses in the nonlinear regime are compared with the predictions of the
      Bautista-Manero-Puig (BMP) model. Model predictions follow the experimental data
      closely.

PMID- 17547935
TI  - Phase behavior of mixed solution of a glycerin-modified cationic surfactant and
      an anionic surfactant.
AB  - The phase behavior of mixed solution of newly synthesized
      monoglycerylcetyldimethylammonium chloride (MGCA) and sodium octyl sulfate (SOS)
      in water was investigated by cryo-transmission electron microscopy (cryo-TEM),
      dynamic light scattering (DLS), differential scanning calorimetry (DSC), and
      fluorescence polarizing for evaluation of the microviscosity of bilayers. No
      precipitate was observed in the mixed solution except at concentrations below 20
      mM over all mixing ratios, and stable vesicles were formed in a considerably wide
      range of mixing ratio, even at the equimolar ratio. Vesicles formed in aqueous
      1/1 MGCA/SOS mixture were found to exhibit no phase transition, and fluorescence
      polarizing measurements showed that the vesicle bilayers have a high fluidity.
      This flexibility allows the bilayers to have a spontaneous curvature, and thus
      vesicles rather than flat lamellae can be stabilized in the mixture even at the
      equimolar ratio. In addition, because the glycerin group of MGCA interacts
      strongly with water, the hydration repulsion contributes to prevent the bilayers
      consisting of MGCA and SOS from adhering and flocculating even though the charge
      neutralization between MGCA and SOS occurs at the equimolar ratio.

PMID- 17547936
TI  - Novel viscoelastic systems from cationic surfactants and hydrophobic counter
      ions: influence of surfactant chain length.
AB  - In continuation of our previous investigations on the aqueous phase behavior of
      cetyltrimethylammonium 2-hydroxy-1-carboxy-naphthoate (CTA-2,1-HCN) (see J.
      Colloid Interface Sci. 288 (2005) 570), we have studied the phase behavior and
      the properties of the phases of the two shorter homologues, C(14)TA-2,1-HCN and
      C(12)TA-2,1-HCN. The phases were prepared from the alkyltrimethylammonium
      hydroxides RTAOH and the naphtholcarboxylic acid. By preparing the systems in
      this way the surfactant solutions contain no excess salt. With increasing counter
      ion-surfactant ratio r we observed the same sequence of phases as for the
      previously studied C(16)-system, namely a L(1)-phase and a L(alpha)-phase with
      multilamellar vesicles (MLV). The single phases are separated by a two-phase
      L(1)/L(alpha) region. The phases were characterized with FF-TEM, rheological and
      SANS measurements. For both systems the viscosity of the L(1)-phases passes with
      increasing counter-ion/surfactant ratio over a maximum. The height of the maximum
      decreases strongly with decreasing chain length while the complex viscosity of
      the MLV-phase depends little on the chain length. For 100 mM solution both MLV
      phases behave like a weak gel and have a yield stress value. It is thus shown
      that it is possible to prepare viscoelastic surfactant solutions with a yield
      stress value from single chain surfactants with a dodecyl chain.

PMID- 17547937
TI  - Super water-repellent poly(alkylpyrrole) films having environmental stability.
AB  - We present electrochemical synthesis of super water-repellent poly(alkylpyrrole)
      films which exhibit excellent environmental stability in terms of contact angle
      (>150 degrees ) for water. The poly(alkylpyrrole) films synthesized under an
      optimized electrochemical condition consisted of thousands of micro-scaled
      'needles' which densely aligned by shoulder to shoulder. The surface of the
      aligned 'needles' was analyzed by a box-counting method, to be a fractal
      structure with a dimension of 2.18.

PMID- 17547938
TI  - The leading edge of evaporating droplets.
AB  - New experiments on drops evaporating in normal atmosphere from smooth substrates
      in the situation of complete wetting are reported and compared with the available
      theoretical model. They are the continuation of previous work with alkane or
      water sessile drops, which is first briefly summarized. The model accounts very
      well for the dynamics of the drop radius, but the predictions are only
      qualitative for the contact angle, especially for small angles. Experiments with
      hanging drops allow us first to discard any influence of convection in the gas
      phase on the drops dynamics. Then the main part of the paper concerns new
      experiments with polydimethylsiloxane oligomers. These silicone oils are similar
      to alkanes as far as evaporation rate is concerned, but have lower surface
      tensions, and therefore smaller dynamic contact angles. The purity of the oils
      appears to be critical for the experiments, and requires a preliminary
      investigation. Then a systematic study of the drops dynamics is presented, as a
      basis for forthcoming theoretical work.

PMID- 17547939
TI  - Formation of intermediate micellar phase between hexagonal and discontinuous
      cubic liquid crystals in brine/N-acylamino acid surfactant/N-acylamino acid oil
      system.
AB  - The phase behavior in the brine/sodium N-dodecanoyl sarcosinate (Sar)/isopropyl N
      dodecanoyl sarcosinate (SLIP) system has been investigated by means of phase
      study, static light scattering, and small-angle X-ray scattering. The liquid
      crystal phases, hexagonal (H(1)) and discontinuous cubic (I(1)), melt upon the
      addition of NaCl, which shows the similar effect to the increasing of
      temperature. The addition of SLIP to the brine/Sar solution at high Sar
      concentration induces the phase transition from H(1) to I(1) via the isotropic
      micellar solution (W(m2)). The micellar structure in the W(m2) phase also changes
      from the wormlike to the globular micelle with SLIP concentration. Adding NaCl
      reduces the repulsive force between the Sar head groups and simultaneously the
      space of the solubilized SLIP in the palisade layer, leading SLIP to shift their
      location further into the micelle core. As a consequence, the hexagonal symmetry
      breaks into the micelle solution and the liquid crystal order is destabilized
      entropically.

PMID- 17547940
TI  - Fabrication of a maxillary implant-supported overdenture retained by two cemented
      bars: a clinical report.
AB  - Parallel placement of 2 separate bars may be indicated in patients where bone is
      available in the posterior part of the maxilla. Bars and stud attachments are the
      primary attachment systems compatible with the majority of the implant systems
      currently available; however, treatment planning in certain situations may be
      challenging due to the component available with the implant system used. This
      report describes the fabrication of a cemented bar design for use in situations
      when the components of the implant system are inadequate for fabrication of a
      screw-retained bar.

PMID- 17547941
TI  - Management of a patient with severe erosive lichen planus in need of an immediate
      complete denture: a clinical report.
AB  - This clinical report describes the treatment of a patient in need of an immediate
      complete denture who presented with severe erosive lichen planus. In conjunction
      with an immediate complete denture, tacrolimus (0.1%) ointment, an
      immunosuppressive agent, was applied topically over the lesions. There was a
      significant reduction in the size of the lesions at the second week of treatment,
      allowing the patient to tolerate the prosthesis without pain, thereby improving
      her quality of life.

PMID- 17547942
TI  - Facilitation of facial prosthesis placement with tattoo markers: a clinical
      report.
AB  - Proper repeatable alignment of an adhesive-retained auricular prosthesis may be a
      difficult challenge. Usually anatomical undercuts, tissue remnants, and scars are
      used as references to secure a facial prosthesis and provide retention and
      stability. Repeated application may be hindered when none of these references is
      present. This clinical report describes a method of using tattoo marks as
      references to repeatably align the facial prosthesis of a patient with a skin
      flap reconstruction.

PMID- 17547943
TI  - Implant-retained feeding aid prosthesis for a patient following total glossectomy
      and laryngectomy: a clinical report.
AB  - This clinical report describes the prosthetic management of a patient following
      total glossectomy and total laryngectomy that severely compromised his oral
      function, caused facial disfigurement, and limited the patient's quality of life.
      A feeding aid prosthesis was designed to address the patient's chief complaint of
      difficulty in feeding and mastication. The prosthesis was designed as an implant
      retained overdenture with a lingual metal plate to facilitate food introduction
      into the oropharynx. This treatment improved mastication, appearance, and the
      quality of the patient's social life.

PMID- 17547944
TI  - Flexure strength evaluation of a laboratory-processed fiber-reinforced composite
      resin.
AB  - STATEMENT OF PROBLEM: A fiber-reinforced composite resin system has been
      introduced for posterior restorations; however, little information is known
      regarding possible degradation of its flexure strength with respect to aging and
      cyclic loading. PURPOSE: The aim of this in vitro study was to determine whether
      the fiber reinforcement improved the flexure strength of an indirect composite
      resin aged in air and water for 3 months and then subjected to static and cyclic
      loading. MATERIAL AND METHODS: The materials tested in this study, non-fiber
      reinforced composite resin (n=160) (Tescera Dentin) and fiber-reinforced
      composite resin (n=160) (Tescera U-beam and Rod), were fabricated as bars, 25.0 x
      4.5 x 4.5 mm, and polished with 120- to 320-grit silicon carbide grinding paper.
      The static (n=15) and cyclical (n=25) flexure strengths (MPa) of specimens were
      tested initially and after 3 months' aging in air and water. The specimens were
      tested in 3-point loading in their respective aging media at a loading rate of 2
      mm/min. Cyclic testing followed the staircase approach of either 1000 cycles or
      until specimen fracture. Statistical analysis for the static-loaded specimens
      consisted of a 3-way analysis of variance (media, aging, and fiber-reinforced
      versus unreinforced) (alpha=.05), whereas the cyclic-loaded specimens used
      confidence levels of .95 for the respective variables (media, aging, and fiber
      reinforced versus unreinforced) and to compare static versus cyclic loading.
      RESULTS: The statistical analysis of the static specimens showed no significant
      difference between control (unaged) groups and aged groups and aging media, but a
      significant difference (P<.001) between reinforced versus unreinforced specimens.
      For the cyclic-loaded specimens, the confidence levels at .95 showed no
      difference between control (unaged) groups and aged groups and aging media (air
      or water), but a difference between reinforced versus unreinforced specimens, and
      static-loaded versus cyclic-loaded specimens. During testing, the specimens
      separated into several pieces when the fiber reinforcement was on the compressive
      side, whereas the specimen remained intact when the fiber reinforcement was on
      the tensile side. CONCLUSIONS: When compared to indirect composite resin without
      fiber reinforcement, the addition of fibers is an effective method to improve the
      flexure strength of indirect composite resin for the materials tested.

PMID- 17547945
TI  - In vitro evaluation of push-out bond strength of direct ceramic inlays to tooth
      surface with fiber-reinforced composite at the interface.
AB  - STATEMENT OF PROBLEM: Failure of a restoration, where a part of a ceramic inlay
      and/or a cusp is fractured, is a common clinical problem. The application of
      fiber-reinforced composites at the tooth-inlay interface may prevent undesirable
      fractures in dental restorations. There is little information regarding the
      effect of a fiber- reinforced composite layer on the push-out bond strength of
      ceramic inlays to tooth structure. PURPOSE: The purpose of this study was to
      compare push-out bond strengths of ceramic inlays to tooth structure using a
      layer of fiber weave-reinforced composite at the tooth interface with different
      adhesive systems. MATERIAL AND METHODS: Forty standardized occlusal, conically
      shaped cavities, 5 mm in occlusal diameter, 3.5 mm in cervical diameter and 3.5
      mm deep, were prepared in extracted human molars using a truncated cone-shaped
      diamond rotary cutting instrument, the dimensions of which corresponded with
      those of prefabricated ceramic inlays. The teeth were divided into 2 groups
      according to the adhesive system used. Solobond Plus was used as a total-etching
      system and Futurabond NR as a self-etching system. Preetched and silanized
      ceramic inlays were bonded to tooth structure with or without a layer of
      bidirectional fiber weave (StickTech). The groups without fiber-reinforced
      composite layer served as controls. The inlays were cemented with dual
      polymerizing luting composite (Bifix QM) and light polymerized for 40 seconds
      from the buccal, lingual, and occlusal surfaces. Specimens were thermal cycled
      (6000 x 5 degrees -55 degrees C) and 3.5-mm-thick discs were prepared for the
      push-out test. The discs (n=10) were tested in a universal testing machine and
      pushed out with a cross-head speed of 1.0 mm/min. The data were analyzed with
      analysis of variance (ANOVA) (alpha=.05). Failure modes were analyzed using a
      stereomicroscope and SEM. RESULTS: Push-out mean bond strength (SD) values in MPa
      of direct ceramic inlays were: Solobond Plus (control): 9.7 (3.9), Solobond Plus
      with fiber-reinforced composite: 10.5 (5.0), Futurabond NR (control): 8.4 (2.5),
      Futurabond NR with fiber-reinforced composite: 8.6 (2.2). The differences between
      groups were not significant for either adhesive system or with the use of fiber
      reinforced composite layer at the interface. Mixed failures were observed in the
      control groups, whereas in the fiber-reinforced composite layer groups, failures
      were mostly cohesive within the fiber layer. No cohesive fracture of the tooth
      was observed when a layer of fiber weave was placed at the interface. CONCLUSION:
      Within the limitations of this in vitro study, a fiber-reinforced composite layer
      at the bonding interface of ceramic inlay did not influence the push-out bond
      strength. Futurabond NR self-etching system and Solobond Plus total-etching
      system demonstrated similar push-out bond strengths.

PMID- 17547946
TI  - Layered color of all-ceramic core and veneer ceramics.
AB  - STATEMENT OF PROBLEM: Color of an all-ceramic restoration is the result of
      interaction between core and veneer ceramics. However, the influence on color of
      the different types of all-ceramic core and veneer combinations at clinically
      relevant thicknesses is not well understood. PURPOSE: The purpose of this study
      was to measure the layered color of all-ceramic core and veneer combinations with
      the thickness of the core set as the clinically minimum thickness to mask the
      background, and the thickness of the veneer set as the remaining available
      thickness within a clinically allowable thickness. MATERIAL AND METHODS: The A2
      corresponding shade of 7 all-ceramic core materials, and 1 sintering ceramic and
      1 alloy core as references, were prepared in clinically minimum thicknesses (0.4
      to 0.8 mm) to mask the background (n=7). The A2 and A3 corresponding shades of
      each recommended veneer ceramic were used to fabricate specimens that were 1.5 mm
      thick. The color of the core, veneer, and layered specimens was measured with a
      reflection spectrophotometer. Two-way ANOVA with the independent variables of the
      types of core and veneer ceramics on the layered color was used to analyze the
      data (alpha=.05). The influence of the color coordinates in the core and
      veneering ceramics on the layered color was analyzed with multiple regression
      analysis. RESULTS: CIE L( *), a( *), b( *), and C( *)(ab) values of A2- or A3
      veneer layered specimens were influenced significantly by the combination of core
      and veneer ceramics (P<.001). The CIE L( *) values of layered specimens were
      primarily influenced by the CIE L( *) values of the core ceramic (P<.001). The
      other 3 parameters were primarily influenced by each corresponding parameter of
      veneer ceramic, based on multiple regression analyses (P<.001). CONCLUSION: The
      layered color of all-ceramic core and veneer ceramics in the clinically allowable
      thickness was different even when the same shade, keyed to a VITA guide, of core
      and veneer ceramics were layered. The color difference between each pair of A2-
      or A3-veneered specimens by the combination of core and veneer ceramics ranged
      from 1.4 to 5.6 DeltaE( *)(ab) units.

PMID- 17547947
TI  - Survey of prosthodontic service provided by general dentists in Virginia.
AB  - STATEMENT OF PROBLEM: Activities in prosthodontic treatment may be changing due
      to prevalence of disease and new treatment options. Studies cite conflicting
      evidence in regard to prosthodontic services, particularly removable
      prosthodontics. PURPOSE: This project was designed to describe the amount of
      prosthodontic services provided by general dentists in Virginia. Results may
      enhance understanding practice patterns in Virginia and regions with similar
      demographics. MATERIAL AND METHODS: Licensed Virginia dentists (n=600) were
      randomly selected from the Virginia Department of Health Professions website.
      Each individual was mailed a survey of questions about his or her demographics
      and practice activities with regard to prosthodontics. RESULTS: Of the 333
      respondents, 195 provide prosthodontic treatment and function as general
      dentists. On average, they spend 25% of their practice time providing
      prosthodontic services (17% fixed and 8% removable). They provide at least 1
      complete denture for a mean total of 24.3 patients per year, at least 1 removable
      partial denture for a mean total of 28.7 patients per year, at least 1 fixed
      partial denture for a mean total of 23.0 patients per year, at least 1 implant
      supported crown for a mean total of 12.3 patients per year, and at least 1
      implant-supported fixed partial denture for mean total of 3.3 patients per year.
      Data were analyzed using descriptive statistics. Data for total population and
      median income were analyzed with the Wilcoxon signed rank test. CONCLUSION:
      Virginia dentists continue to provide considerable numbers of fixed prosthodontic
      restorations, removable partial dentures, and complete dentures, while providing
      a growing number of implant-supported restorations.

PMID- 17547948
TI  - A randomized clinical trial comparing anatomic, lingualized, and zero-degree
      posterior occlusal forms for complete dentures.
AB  - STATEMENT OF PROBLEM: There is a lack of evidence to recommend a particular type
      of posterior occlusal form for conventional complete dentures. PURPOSE: The
      purpose of this study was to compare subject satisfaction with 3 types of
      posterior occlusal forms for complete dentures in a randomized cross-over
      controlled trial. MATERIAL AND METHODS: For each participant (n=45), 3 sets of
      complete dentures were fabricated, each of which had a different posterior
      occlusal form (0-degree, anatomic, and lingualized). Each set was worn for 8
      weeks in a randomized order. Subjective data were collected using the Oral Health
      Impact Profile 20-EDENT (OHIP-EDENT). The Wilcoxon statistical test was used to
      compare differences between the groups (alpha=.05). RESULTS: Lingualized
      posterior occlusal forms were perceived to be significantly superior in terms of
      painful aching in the mouth (P=.01), sore spots (P<.001), eating ability (P=.02),
      and meal interruptions (P=.008), compared with 0-degree posterior occlusal forms.
      Subjects with anatomic posterior occlusal forms had significantly fewer problems
      eating (P=.05) compared with 0-degree posterior occlusal forms. There was no
      significant difference found between the lingualized and anatomic posterior
      occlusal forms. CONCLUSIONS: Participants provided with complete dentures having
      lingualized or anatomic posterior occlusal forms exhibited significantly higher
      levels of self-perceived satisfaction compared to those with 0-degree posterior
      occlusal forms.

PMID- 17547949
TI  - The strength of multiple major connector designs under simulated functional
      loading.
AB  - STATEMENT OF PROBLEM: The design of a removable dental prosthesis (RDP) must
      balance functional strength, comfort to the patient, and the health of the
      tissue. While research has been conducted to enhance the strength of major
      connectors, little has been done to determine if the dimensions of major
      connectors can be reduced in order to enhance patient comfort and tissue health.
      PURPOSE: The purpose of this study was to determine the minimum major connector
      dimensions of 1 mandibular and 2 maxillary major connectors that would provide
      adequate functional strength. MATERIAL AND METHODS: Sixty chromium-cobalt alloy
      (Vitallium) RDP frameworks were fabricated. The major connector designs were: a
      mandibular lingual bar, a maxillary palatal strap, and a maxillary anterior
      posterior (A-P) palatal strap. Four groups of 5 frameworks with diminishing
      dimensions were fabricated for each major connector design. The lingual bar was
      tested at 4, 3, 2.5, and 2 mm in height, occlusogingivally, and 1.6 mm in
      thickness; the palatal strap at 8, 6, 4, and 2 mm, anteroposteriorly; and the A-P
      palatal strap at 10 x 6, 8 x 4, 6 x 2.5, and 4 x 2 mm, anteroposteriorly. All
      maxillary frameworks were 0.65 mm in thickness. The frameworks were of a Kennedy
      Class II Mod I design with 3 widely separated vertical reference points to
      measure deformation. Two tests were conducted to evaluate the functional strength
      for each framework. The first test was masticatory simulation, or torsional
      force. The second test was a drop test from a height of 3 feet. Permanent
      deformation was then determined after each test. The Cochran-Armitage test
      (alpha=.05) was used for both the torsion test and the drop test. RESULTS: A
      statistically significant difference in permanent deformation was found for the
      palatal strap design among the 4 different dimensions for the compressive test
      (P=.015) and the drop test (P=.044). CONCLUSION: It is safe to reduce the
      dimensions of some major connectors under normal loads. The reduced size of the
      connectors places the removable partial denture at increased risk for deformation
      when dropped from a height.

PMID- 17547950
TI  - Association between anterior tooth wear and temporomandibular disorder pain in a
      German population.
AB  - STATEMENT OF PROBLEM: Bruxism is purported to be a risk factor for
      temporomandibular disorder (TMD) pain, but the association requires
      clarification. PURPOSE: The purpose of this study was to investigate the relation
      between anterior tooth wear as an indicator for bruxism and the presence of TMD
      pain. MATERIAL AND METHODS: Study subjects included 646 participants (age range
      35 to 44 years) of a national oral health survey in Germany. Anterior tooth wear
      was registered for each anterior tooth with a 4-point scale (none, mild,
      moderate, and severe wear). Temporomandibular disorder was defined as self
      reported pain in the face, jaw muscles, and/or temporomandibular joint (TMJ)
      during the last month, according to either the German version of the Research
      Diagnostic Criteria for Temporomandibular Disorders or the response to a question
      about pain in the masticatory muscles or the TMJ according to the Helkimo-Index.
      A multiple logistic regression analysis, controlling for the effects of age and
      gender, investigated the linear relationship between increased tooth wear and the
      risk of TMD pain. RESULTS: After adjusting for age and gender, an odds ratio of
      1.11 (95% confidence interval: 0.7-1.8) indicated that the risk of TMD pain
      increased an estimated 11% per unit increase of tooth wear. There was no
      statistically significant or clinically relevant relationship between a linear
      increase of tooth wear and risk of TMD pain. CONCLUSION: Anterior tooth wear was
      not associated with self-reported TMD pain in 35- to 44-year-old subjects. Using
      anterior tooth wear as an indicator for long-term bruxing behavior, a clinically
      relevant dose-response relationship between this type of bruxism and TMD pain
      does not appear to exist.

PMID- 17547951
TI  - Radiographic and surgical guide for placement of multiple implants.

PMID- 17547952
TI  - A simple, permanent index for abutment screw access for cemented implant
      supported crowns.

PMID- 17547953
TI  - Cement-retained bar attachment system for implant-retained mandibular
      overdentures.

PMID- 17547968
TI  - Proceedings of the Ninth International Symposium on Neurobehavioral Methods and
      Effects in Occupational and Environmental Health. Gyeongju, Korea. September 26
      29, 2005.

PMID- 17547971
TI  - Antiviral agents for the treatment of recurrent respiratory papillomatosis: a
      systematic review of the English-language literature.
AB  - OBJECTIVE: To determine the efficacy of antiviral agents for recurrent
      respiratory papillomatosis (RRP) in children and adults. STUDY DESIGN: Systematic
      review to include randomized controlled trials (RCTs), comparative studies
      (historical and/or nonrandomized), case series, and case reports. RESULTS: Twenty
      six original studies were included (one case-control series, 21 noncomparative
      trials, four case reports, and no RCTs). Meta-analysis was not possible. The
      antiviral modalities included acyclovir, ribavirin, intravenous cidofovir, and
      intralesional cidofovir injections. The strongest evidence was for intralesional
      cidofovir, with 17 studies including 158 patients. Of these, 90 patients (57%)
      demonstrated complete resolution, 55 patients (35%) a partial response, and 13
      patients (8%) showed no improvement. CONCLUSIONS: Insufficient evidence from
      controlled trials exists for reliable conclusions, but several series indicate
      intralesional cidofovir may have some efficacy. A well-designed placebo
      controlled, double-blinded, randomized controlled trial is needed. SIGNIFICANCE:
      This study provides the background for future study design and a comprehensive
      review of the available evidence.

PMID- 17547972
TI  - Surgical and medical management of midline ectopic thyroid.

PMID- 17547973
TI  - The voice and laryngeal dysfunction in stroke: a report from the Neurolaryngology
      Subcommittee of the American Academy of Otolaryngology-Head and Neck Surgery.
AB  - OBJECTIVE: Stroke is the third leading cause of death in the United States,
      behind heart disease and cancer. It affects as many as 5% of the population over
      65 years old, and this number is growing annually due to the aging population. A
      significant portion of stroke patients that initially survive are faced with the
      risk of aspiration, as well as quality-of-life issues relating to impaired
      communication. The goal of this paper is to define the scope of practice in
      otolaryngology for these patients, and to review pertinent background literature.
      STUDY DESIGN: Consensus report and retrospective literature review. RESULTS:
      Otolaryngology involvement in these patients is critical to their rehabilitation,
      which often requires an interdisciplinary team of specialists. This committee
      presentation explores epidemiological data regarding the impact of stroke and its
      complications on hospitalizations. A pertinent review of neuroanatomy as it
      relates to laryngeal function is also discussed. State-of-the-art diagnostic and
      therapeutic procedures are presented. CONCLUSION: There is a well-defined set of
      diagnostic and therapeutic options for laryngeal dysfunction in the stroke
      patient. SIGNIFICANCE: Otolaryngologists play a critical role in the
      interdisciplinary rehabilitation team.

PMID- 17547974
TI  - Aminolevulinic acid 585 nm pulsed dye laser photodynamic treatment of laryngeal
      keratosis with atypia.
AB  - OBJECTIVE: To evaluate the safety and efficacy of aminolevulinic acid
      photodynamic therapy (ALA-PDT) with the 585 nm pulsed dye laser. METHODS: A 5
      year prospective study was performed with 12 male patients with keratosis. Twenty
      percent ALA was sprayed into the larynx and activated with the 585 nm pulsed dye
      laser (PDL). Of the 12 patients, four were not included (one lost to follow-up,
      two developed cancer, one papillomatosis), which reduced the number to eight.
      Twenty-eight procedures were performed in these eight patients; 18 (64%)
      procedures were performed in the clinic setting. RESULTS: There was a 78%
      reduction (range, 10% to 100%) in the keratosis. No major side effects were
      noted. Mean follow-up was 34.5 months (range, 12 to 50 months). There were no
      statistical differences between the outpatient and operating room treatments.
      CONCLUSIONS: ALA-PDL PDT is effective and safe in treating laryngeal keratosis in
      the awake clinic setting and reduces morbidity without sacrificing treatment
      efficacy.

PMID- 17547975
TI  - Phonatory function of the elderly determined by intensity-loading test: a
      comparison with the young.
AB  - OBJECTIVE: The goal was to test the hypothesis that the elderly have diminished
      laryngeal regulation capability, so we investigated phonatory function in the
      elderly and young using a sound pressure-loading test. STUDY DESIGN AND SETTING:
      In 36 healthy men (17 in their 20s, 19 in their 70s) and 45 healthy women (22 in
      their 20s, 23 in their 70s), fundamental frequency, sound pressure level, mean
      flow rate (MFR), and expiratory lung pressure (EP) were determined from phonatory
      function testing. Subjects phonated at a comfortable level and at high intensity,
      without changing vocal pitch. RESULTS: MFR, EP, and airway resistance increased
      with high-intensity phonation in the young; however, only MFR and EP increased in
      the elderly. CONCLUSIONS: The findings supported our hypothesis: with high
      intensity phonation, the elderly undergo unchanged laryngeal regulation but a
      greater degree of expiratory regulation. SIGNIFICANCE: The elderly are likely to
      become tired due to the effort required for phonation.

PMID- 17547976
TI  - Relationship of botulinum dosage to duration of side effects and normal voice in
      adductor spasmodic dysphonia.
AB  - OBJECTIVE: Objective evaluation of botulinum toxin A (BTX-A) dosing by
      determination of the statistical relationship between injection amount and
      duration of side effects and normal voice in adductor spasmodic dysphonia (SD)
      patients. From this information, to provide a rational guide to determine the
      initial and follow-up BTX-A amounts for injection. STUDY DESIGN AND SETTING:
      Private laryngology clinic. Statistical analysis was performed on data obtained
      from 101 patients with SD. RESULTS: Significant and predictable positive
      correlations were found between duration of side effects and duration of normal
      voice after BTX-A injection in patients with SD. Dose of BTX-A injected also
      appeared to have a significant positive correlation with duration of side
      effects, but a negative correlation with duration of normal voice. A trend toward
      more severe side effects was seen with larger doses of BTX-A injections.
      CONCLUSIONS AND SIGNIFICANCE: Increased understanding of the response of the
      human voice over time after BTX-A injection at various doses suggests new ideas
      to further increase clinical efficacy with the use of lower BTX-A doses.

PMID- 17547977
TI  - Transoral laser microsurgery for carcinoma of the supraglottic larynx.
AB  - OBJECTIVES: The study goal was to report the oncologic outcomes of transoral
      laser microsurgery (TLM) in the treatment of squamous cell carcinoma of the
      supraglottic larynx. STUDY DESIGN AND SETTING: A two-center prospective case
      series analysis. RESULTS: Thirty-eight patients underwent TLM for previously
      untreated carcinoma of the supraglottic larynx between 1997 and 2005.
      Pathological T stages were T1 in 8 (21%), T2 in 14 (37%), T3 in 8 (21%), and T4
      in 8 (21%). Twenty-six patients (68%) had neck dissections. Thirteen patients
      (34%) received adjuvant radiotherapy. The mean follow-up for all patients was 31
      months. The 2-year Kaplan-Meier estimates for local control were 97%;
      locoregional control, 94%; disease-specific survival, 80%; and overall survival,
      85%. The overall functional laryngeal preservation rate was 79% (19 of 24).
      CONCLUSIONS: TLM is a safe and effective treatment for cancer of the supraglottic
      larynx. SIGNIFICANCE: TLM is an emerging strategy in the management of laryngeal
      cancer.

PMID- 17547978
TI  - Template-based registration for image-guided skull base surgery.
AB  - OBJECTIVES: To evaluate whether patient-to-image registration with the use of a
      maxillary template is sufficiently accurate for image guided skull base surgery.
      STUDY DESIGN AND SETTING: In an experimental phantom study, pair-point
      registration of a skull phantom to its CT image data was performed with 243
      different configurations of a maxillary template with markers. Then artificial
      skull mounted target markers were located with an infrared tracking device as
      used in navigation systems. RESULTS: The average target registration error was
      1.57 mm in the anterior skull base (95% confidence interval, 1.53 to 1.61 mm),
      but 3.31 mm in the lateral skull base (95% confidence interval, 3.26 to 3.37 mm).
      CONCLUSIONS: Fiducial marker registration based on a maxillary template is
      sufficiently accurate for image-guided surgery in the anterior skull base, but
      not for the lateral skull base. SIGNIFICANCE: Template-based registration is an
      accurate yet noninvasive registration method for frontal skull base surgery.

PMID- 17547979
TI  - Role of free tissue transfer in skull base reconstruction.
AB  - OBJECTIVE: Free tissue transfer to the skull base provides a watertight seal to
      prevent CSF leakage and donor tissue tailored to the individual defect. STUDY
      DESIGN AND SETTING: Retrospective chart review of 38 patients who underwent free
      tissue transfer to the skull base between November 1995 and October 2005 at an
      academic, tertiary referral center. RESULTS: There were 23 male and 15 female
      patients (average age, 58.1 years) with skull base defects resulting from
      oncologic resection or head trauma most frequently. Donor sites included the
      radial forearm (25), rectus abdominis (12), latissimus dorsi (4), anterolateral
      thigh, scapula, serratus anterior, and ulna (1 each). Seven patients required a
      second free tissue transfer indicated for flap death (3), partial flap necrosis
      (2), pneumocephalus (1), or tumor recurrence (1). Two patients died in the
      immediate postoperative period. CONCLUSIONS: Free tissue transfer is a robust
      option in the repair of post-surgical and post-traumatic skull base defects.

PMID- 17547980
TI  - Surgical outcomes and safety of transnasal endoscopic resection for anterior
      skull tumors.
AB  - OBJECTIVE: To report the surgical outcomes and safety of transnasal endoscopic
      resection (TER) for anterior skull base (ASB) tumors. STUDY DESIGN AND SETTING: A
      retrospective chart review to identify patients undergoing TER for ASB tumors at
      a tertiary care medical center between September 1997 and June 2006. RESULTS:
      Nineteen patients underwent TER for ASB tumors without open craniotomy. There
      were 17 malignant and two benign lesions. Olfactory neuroblastoma was the most
      common pathology, occurring in 53 percent of patients. One patient recurred
      locally, resulting in an overall local control rate of 94.7 percent for all
      neoplasms and 94.1 percent for malignant disease. It should be noted that the
      tumor control rate may be premature given the small sample size and limited
      follow-up. Overall, there were 16 complications, but only two of these, an
      orbital hematoma and a frontal lobe abscess, were considered major complications
      directly attributable to surgery. CONCLUSIONS: TER for ASB tumors appears to be
      safe in properly selected patients. In light of the small sample size and limited
      follow-up, the major complication rate directly attributable to surgery was 11
      percent, and the overall local control rate was 95 percent. A larger multi
      institutional series with longer follow-up is warranted.

PMID- 17547981
TI  - A clinicoradiologic analysis of symptomatic craniofacial fibro-osseous lesions.
AB  - OBJECTIVE: To outline the clinical and radiologic aspects of symptomatic
      craniofacial fibro-osseous lesions and to study the appropriate surgical
      management with follow-up results. STUDY DESIGN AND SETTING: A retrospective
      review of 11 patients who underwent surgical treatment during 1985 to 2004 in a
      tertiary health care center. RESULTS: Most (72.7%) cases were of fibrous
      dysplasia and were under 25 years of age (72%). Maxilla was the most common bone
      involved (81%). Lateral rhinotomy was the main approach for surgical resection.
      One patient underwent bilateral optic nerve decompression (left side therapeutic
      and on right side prophylactic). Six (54.5%) cases had recurrences that were
      managed by either radical surgery (total maxillectomy) or by further shaving off
      the lesion. CONCLUSION: Treatment of craniofacial fibro-osseous lesions is highly
      individualized. A conservative approach may not be able to treat all cases of
      craniofacial fibro-osseous lesions. A more radical approach that includes a
      craniofacial resection or a total maxillectomy may be warranted in few cases.

PMID- 17547982
TI  - 100 consecutive collaborative percutaneous tracheostomies.
AB  - OBJECTIVES: We previously introduced the concept of the collaborative
      percutaneous tracheostomy (PercTrach) performed in conjunction with pulmonary
      medicine/critical care (PCC), and now present a robust experience that validates
      our original concept of exploiting subspecialty expertise. METHODS: One hundred
      consecutive PercTrachs were performed. The PCC team performed bronchoscopic
      guidance, while the otolaryngology team performed the PercTrach using the Blue
      Rhino introducer set. Demographic data were gathered. RESULTS: One hundred
      PercTrachs were performed between May 2003 and December 2005. The mean +/- SD
      patient age was 54.3 +/- 15.9 years. Procedural times ranged from 5 to 37
      minutes, with a mean of 12.9 +/- 5.7 minutes. Surgical complications included one
      patient with bleeding who required surgical intervention. CONCLUSIONS AND
      SIGNIFICANCE: There are numerous benefits to capitalizing on the respective
      expertise represented by otolaryngology and PCC including conservation of
      operating room time, rapid and safe establishment of the tracheostomy, and
      educational benefits for both programs.

PMID- 17547983
TI  - Percutaneous dilation tracheotomy in intensive care unit patients.
AB  - OBJECTIVES: In our department, we routinely use percutaneous dilation tracheotomy
      (PDT) in select intensive care unit (ICU) patients requiring prolonged intubation
      and mechanical ventilation. We present our experience with this technique and
      discuss the pros and cons of PDT in the intensive care setting. STUDY DESIGN AND
      SETTING: We conducted a retrospective study of consecutive PDTs performed in our
      institution between 2002 and 2004. Demographic information and procedural and
      postoperative complications were noted. RESULTS: Two hundred seventy-four PDTs
      were performed on intensive care unit patients during this time period.
      Complications included five cases of excessive intraoperative bleeding (1.8%),
      one postoperative hemorrhage (0.3%), one tracheoesophageal fistula (0.3%), one
      pneumothorax (0.3%), and four accidental decannulations (1.4%). No PDT-associated
      deaths occurred. CONCLUSIONS: PDT is advantageous for the patient as it is
      performed at bedside in the ICU. It is our conclusion that this technique is
      suitable for many, but not all, critical care patients.

PMID- 17547984
TI  - The effects of fine-needle biopsy on thyroid hormone levels.
AB  - OBJECTIVE: Our study aim was to investigate the effects of fine-needle biopsy
      used for thyroid nodules on serum thyroid hormone levels. STUDY DESIGN: A total
      of 25 patients who had solid nodules of the thyroid gland and normal thyroid
      hormone levels underwent diagnostic fine-needle biopsy for a nodule of the
      thyroid gland. METHODS: Venous blood samples were drawn from the cases for
      measurement of serum total T(3) and T(4), free T(3) and T(4), thyroid-stimulating
      hormone, and thyroglobulin levels before, immediately after, and 30 minutes after
      the initial biopsy. RESULTS: Total T(3) and thyroglobulin levels were found to be
      significantly higher immediately and 30 minutes following fine-needle aspiration
      biopsy, compared to the baseline levels (P<0.05). CONCLUSION: Preliminary data
      suggest that thyroid hormone levels show a mean increase of about 20% immediately
      after fine-needle aspiration. SIGNIFICANCE: The implication of this finding on
      patient care should be determined on an individual basis.

PMID- 17547985
TI  - Intraoperative PTH: effect of sample timing and vitamin D status.
AB  - OBJECTIVE: To assess the effect of timing of intraoperative parathormone (iPTH)
      samples and 25-hydroxyvitamin D (25-OHD) status on decision-making during
      parathyroidectomy. METHODS: A total of 77 patients with primary
      hyperparathyroidism and iPTH levels (preincision, preremoval, 5 (T5) and 10 (T10)
      minutes postremoval) performed during parathyroidectomy were reviewed. RESULTS:
      Forty-one percent of patients were 25-OHD insufficient. We noted a significant
      correlation between preoperative 25-OHD and preincision iPTH (P=0.002) but not
      iPTH at postremoval levels (T5, P=0.89; T10, P=0.42). When compared with
      preincision iPTH, the use of either the higher preincision or preremoval iPTH
      baseline significantly improves the assay sensitivity from 83% to 93% at T5
      (P=0.01) and 87% to 97% at T10 (P=0.02). Surgical cure was obtained in 98% of
      patients. CONCLUSION: Obtaining preremoval iPTH allowed earlier decision with
      respect to operative completion in 38% of cases. 25-OHD status does not appear to
      significantly affect interpretation of iPTH levels. SIGNIFICANCE: Obtaining both
      baseline levels significantly improves sensitivity in iPTH monitoring.

PMID- 17547986
TI  - Prevalence and patterns of intraoperative nerve monitoring for thyroidectomy.
AB  - OBJECTIVE: To estimate the patterns of use of intraoperative recurrent laryngeal
      nerve (RLN)-monitoring devices during thyroid surgery by otolaryngologists in the
      United States. METHODS: A questionnaire was mailed to 1685 randomly selected
      otolaryngologists, representing approximately half of all otolaryngologists
      currently practicing in the United States. Topics covered included training
      history and current practice setting, use and characteristics of use of RLN
      monitoring during thyroid surgery, as well as history of RLN injury and/or
      subsequent lawsuits. chi(2) test was used to examine associations between monitor
      usage and dependent variables, and odds ratios calculated by logistic regression
      were used to refine the magnitude of these associations. RESULTS: A total of 685
      (40.7%) of questionnaires were returned, and 81 percent (555) of respondents
      reported performing thyroidectomy. Of those, only 28.6 percent (159) reported
      using intraoperative monitoring for all cases. Respondents were 3.14 times more
      likely to currently use intraoperative monitoring if they used it during their
      training. Surgeons currently using intraoperative RLN monitoring during
      thyroidectomy were 41 percent less likely to report a history of permanent RLN
      injury. Further information about surgeon background and rationale for decisions
      regarding RLN monitor usage are discussed. CONCLUSIONS: Presently, the majority
      of otolaryngologists in the United States do not report regular usage of RLN
      monitoring in their practices. Surgeon background and training, more so than
      surgical volume, significantly influenced the use of intraoperative RLN
      monitoring.

PMID- 17547987
TI  - Is the type of dissection in lateral neck metastasis for differentiated thyroid
      carcinoma important?
AB  - OBJECTIVE: This study was to compare the types of therapeutic neck dissection in
      patients with differentiated thyroid carcinoma. STUDY DESIGN AND SETTING: Sixty
      one patients with lymph node metastasis in the neck, treated between 1997 and
      2001, were studied retrospectively. A comparative study was made of a selective
      lateral neck dissection group and a radical or modified radical neck dissection
      group for recurrence, disease free survival (DFS), and overall survival (OS).
      RESULTS: Type of dissection was not related to DFS (P=0.92), OS (P=0.33), and
      local recurrence ratio (P=0.56). The factors affecting local recurrence were the
      age over 45 years (P=0.02), tumor size (0.005), and the presence of distant
      metastasis (P=0.04). The factors affecting DFS and OS were tumor size (0.003),
      thyroid capsule invasion (0.004). CONCLUSIONS: Determination of the type of
      therapeutic neck dissection depends on patient and tumor characteristics.
      Selective lateral neck dissection can be applied safely in selected cases.

PMID- 17547988
TI  - Idiopathic temporal bone encephaloceles in the obese patient.
AB  - OBJECTIVES: Our aims were to introduce temporal bone encephalocele (TBE) to the
      differential diagnosis of persistent middle ear effusion, cerebrospinal fluid
      otorrhea, or chronic otitis media in obese adults and to demonstrate the basic
      pathophysiologic principles of morbid obesity as it may lead to the cascade of
      increased intra-abdominal pressure, increased central venous pressure, benign
      increased intracranial pressure, and TBE. METHODS: A retrospective review of the
      medical records was performed to determine the location, nature, and etiology of
      the encephaloceles identified at our institution from 1989 to 2005. Body mass
      index was calculated from the patient height and weight data. RESULTS: Eight
      patients with spontaneous, idiopathic TBE were identified. Body mass index values
      ranged from 32.0 to 67.5 kg/m(2) with a mean of 48.6 kg/m(2). All patients
      identified with a spontaneous, idiopathic TBE were obese. CONCLUSION: TBE is
      associated with morbid obesity in our population and should be considered in the
      differential diagnosis when evaluating mastoid and middle ear disease in the
      morbidly obese.

PMID- 17547989
TI  - Comparing pure-tone audiometry and auditory steady state response for the
      measurement of hearing loss.
AB  - OBJECTIVE: To compare pure-tone audiometry and auditory steady state response
      (ASSR) to measure hearing loss based on the severity of hearing loss in
      frequencies. STUDY DESIGN AND SETTING: A total of 105 subjects (168 ears, 64 male
      and 41 female) were enrolled in this study. We determined hearing level by
      measurement of pure-tone audiometry and ASSR on the same day for each subject.
      RESULTS: Pure-tone audiometry and ASSR were highly correlated (r=0.96). The
      relationship is described by the equation PTA=1.05 x mean ASSR - 7.6. When
      analyzed according to the frequencies, the correlation coefficients were 0.94,
      0.95, 0.94, and 0.92 for 0.5, 1, 2, and 4 kHz, respectively. CONCLUSION: From
      this study, authors could conclude that pure-tone audiometry and ASSR showed very
      similar results and indicated that ASSR may be a good alternative method for the
      measurement of hearing level in infants and children, for whom pure-tone
      audiometry is not appropriate.

PMID- 17547990
TI  - The large vestibular aqueduct: a new definition based on audiologic and computed
      tomography correlation.
AB  - OBJECTIVE: The study goal was to determine the prevalence and clinical
      significance of a large vestibular aqueduct (LVA) in children with sensorineural
      hearing loss (SNHL). STUDY DESIGN AND SETTING: We conducted a retrospective
      review of a pediatric SNHL database. One hundred seven children with SNHL were
      selected and their radiographic and audiometric studies were evaluated.
      Radiographic comparisons were made to a group of children without SNHL. RESULTS:
      A vestibular aqueduct (VA) larger than the 95th percentile of controls was
      present in 32% of children with SNHL. Progressive SNHL was more likely to occur
      in ears with an LVA and the rate of progressive hearing loss was greater than in
      ears without an LVA. The risk of progressive SNHL increased with increasing VA
      size as determined by logistic regression analysis. CONCLUSIONS: An LVA is
      defined as one that is >or=2 mm at the operculum and/or >or=1 mm at the midpoint
      in children with nonsyndromic SNHL. An LVA appears to be more common than
      previously reported in children with SNHL. A linear relationship is observed
      between VA width and progressive SNHL. SIGNIFICANCE: The finding of an LVA in
      children with SNHL provides diagnostic as well as prognostic information.

PMID- 17547991
TI  - Chorda tympani injury: operative findings and postoperative symptoms.
AB  - OBJECTIVES: This study aims to assess whether operative findings of chorda
      tympani nerve (CTN) trauma correlate with postoperative symptoms. STUDY DESIGN
      AND SETTING: A prospective study was conducted over 2 years on 140 middle ear
      operations analyzing taste disturbances. The operations were subdivided into
      myringoplasty/tympanoplasty (56 cases), mastoidectomy (64 cases), and tympanotomy
      (20 cases). RESULTS: Twenty-one (15%) patients reported taste disturbance.
      Altered taste was most reported (n=15, 71%) with loss of taste reported by 29%
      (n=6). Symptoms were most observed in the tympanotomy group (45%). Stretching of
      the CTN was associated with more symptoms than nerve transection. Recovery was
      complete in 76% (n=16) of the symptomatic cases by 12 months. CONCLUSION:
      Patients who undergo middle ear surgery should be thoroughly counseled with
      respect to CTN injury and symptoms regardless of the type of damage to the nerve.
      SIGNIFICANCE: This study highlights the high incidence of postoperative
      alterations in taste after middle ear surgery, especially in non-diseased ears,
      and that CTN transection results in fewer symptoms than CTN stretching.

PMID- 17547992
TI  - Type III cartilage "shield" tympanoplasty: an effective procedure for hearing
      improvement.
AB  - OBJECTIVE: To report the hearing results following type III cartilage "shield"
      tympanoplasty. STUDY DESIGN: Retrospective chart review at a tertiary referral
      center. METHODS: Conchal cartilage, shaped as a shield, was used to replace the
      entire tympanic membrane and reconstruct the ossicular chain in patients with an
      absent incus and diminished space between the stapes superstructure and malleolar
      manubrium. RESULTS: Between January 1998 and June 2005, 52 patients were treated.
      The mean age was 32.4 years (range, 7 to 72 years). The mean follow-up was 24
      months (range, 12 to 36 months). Graft take was successful in all patients. The
      average hearing improvement was 11.22 dB (P<0.0001). An air-bone gap of 25 dB or
      less was achieved in 41 (78.8%) patients. Speech discrimination scores remained
      unchanged. No complications were identified. CONCLUSION: Type III cartilage
      "shield" tympanoplasty is an effective technique for hearing improvement in
      selected patients with chronic otitis media. The results of this procedure are
      similar to those obtained with partial ossicular replacement prosthesis.

PMID- 17547993
TI  - Epstein-Barr virus DNA detection in the diagnosis of nasopharyngeal carcinoma.
AB  - OBJECTIVES: This study examines the presence of Epstein-Barr virus (EBV) in
      nasopharyngeal carcinoma (NPC) by using polymerase chain reaction (PCR). STUDY
      DESIGN: Eighty-six postnasal biopsy samples and 71 fine-needle aspirate samples
      of neck masses were obtained from patients who were clinically suspect for NPC.
      Genomic DNA was extracted from the samples, and EBNA1, EBNA2, and LMP genes of
      EBV were detected by PCR. PCR results were compared with NPC histopathology
      findings. RESULTS: The sensitivity of PCR to detect EBNA1 (97.14%), EBNA2
      (88.57%), and LMP (91.43%) genes of EBV in nasopharyngeal biopsy samples were
      higher than those in fine-needle aspirate samples. CONCLUSION: Detection of EBV
      by PCR in tissue obtained from nasopharyngeal biopsy and fine-needle aspirate
      samples of neck masses is a relatively inexpensive, reliable, and accurate method
      of diagnosing NPC. Detection of EBV genes is on par with histopathological
      examination (HPE) and superior to fine-needle aspirate cytology. SIGNIFICANCE:
      PCR is an ideal tool for suggesting NPC and guiding the diagnostic workup in
      occult primary tumors, facilitating earlier diagnosis and reducing morbidity and
      mortality.

PMID- 17547994
TI  - Plasma Epstein-Barr virus immunoglobulin A and DNA for nasopharyngeal carcinoma
      screening in the United States.
AB  - OBJECTIVE: To examine the Epstein-Barr virus (EBV) IgA and DNA assays as a
      screening tool for nasopharyngeal carcinoma (NPC) in a nonendemic US population.
      STUDY DESIGN AND SETTING: Prospective study performed at a teaching hospital in
      New York City. There were two groups of 155 patients: new NPC patients and
      controls. An otolaryngologic examination and serial blood testing for serologic
      markers were performed. RESULTS: Sensitivity and specificity of EBV IgA and DNA
      assays were determined. Screening scenarios involving series and parallel testing
      were evaluated to determine economic feasibility. Series testing provided a
      sensitivity, specificity, and positive and negative predictive values of 90.6,
      93.5, 78.4, and 97.5 percent, respectively. Parallel testing increased the
      sensitivity to 100 percent. CONCLUSION: NPC screening in a high-risk, nonendemic
      population using EBV-specific serologic markers is effective. Series testing is a
      statistically sound and economically feasible strategy. SIGNIFICANCE: The
      development of a cost-effective NPC screening strategy in a high-risk, nonendemic
      population in the United States.

PMID- 17547995
TI  - Combined modality therapy of esthesioneuroblastoma.
AB  - OBJECTIVE: Esthesioneuroblastoma (ENB) is a rare tumor of the olfactory
      epithelium. The objective of this study was to evaluate treatment modalities
      including surgery, IMRT, and chemotherapy and patient outcomes. PATIENTS AND
      METHODS: A retrospective analysis was performed on a total of 21 patients.
      Therapy included craniofacial resection (CFR), radiotherapy, chemotherapy, or a
      combination of these methods. RESULTS: The median follow-up period was 47 months.
      Surgery was performed in 90.4% of cases; radiotherapy was performed adjuvantly in
      15 (72.7%) patients. Surgery, radiotherapy, and chemotherapy were administered to
      7 (33.3%) patients. Eight (38.3%) patients had local recurrence. The 5-year crude
      overall survival was 71.4% and actuarial 5-year overall survival was 58% with
      confidence interval (CI, 25 and 81, respectively). The 5-year crude disease-free
      survival rate was 59% and the 5-year actuarial disease-free survival rate was 62%
      (CI, 28 and 83, respectively). CONCLUSION: Multidisciplinary therapy of ENB
      should be considered, especially for Kadish C and high-grade lesions.
      Craniofacial resection (CFR), Intensity modulated radiation therapy (IMRT), and
      chemotherapy should be investigated in a multi-institution trial of ENB.

PMID- 17547996
TI  - Combined therapy after superselective arterial cisplatin infusion to treat
      maxillary squamous cell carcinoma.
AB  - OBJECTIVE: We sought to assess the efficacy of combined therapy after
      superselective arterial cisplatin infusion (SACI) therapy to treat the maxillary
      squamous cell carcinoma. STUDY DESIGN: We conducted a retrospective chart review
      of 50 patients. After completion of two courses of SACI, 25 of the patients were
      successively treated by concurrent SACI and radiotherapy (AR), while the other 25
      patients were treated by surgery with postoperative radiotherapy (ASR). RESULTS:
      Patients with surgery (ASR) had an 88% local control rate with 75% disease-free
      survival rate at 60 months by Kaplan-Meier analysis, compared with 62% disease
      free survival rate for patients with AR treatment. A particularly good outcome
      was obtained in T4 cases of the ASR group (n=8) whose 5-year survival rate was
      87% and local control rate was 100%. CONCLUSION/SIGNIFICANCE: Combined SACI
      therapy is very effective for the treatment of maxillary squamous cell carcinomas
      and contributes to the improving prognoses of patients and organ preservation
      rates.

PMID- 17547997
TI  - Fate of mucosal healing in transplanted deep frozen irradiated tracheal
      homograft.
AB  - OBJECTIVE: Deep-frozen irradiated tracheal homograft has been successfully
      employed for subglottic-tracheal reconstruction, as in our previous report.
      Morphologically, though the transplanted site appeared to have good mucosal
      healing, the fate of the donor mucosa is not known. The objective of this study
      was to determine the survival of the mucosa of donor trachea. STUDY DESIGN AND
      SETTING: University hospital-based, prospective study. METHODS: Thirty samples
      from six sets of specimens, each set consisting of five samples of the tracheal
      mucosa, were studied. Of five samples in each set, 2 were taken from donors, one
      from a recipient, and another two from the transplanted sites, eight months
      postoperatively. The samples in each set of specimens were genetically matched by
      the process of DNA fingerprinting. Histological studies were done on the mucosa
      of donor and transplanted sites. RESULTS: The study demonstrated incompatibility
      between samples from recipient and transplanted site, and incompatibility between
      preoperative donor and recipient samples in all sets of specimens. CONCLUSION:
      The mucosa of donor trachea did not survive at the transplanted site. The
      apparently normal postoperative mucosal lining actually represents migration of
      the recipient mucosa. SIGNIFICANCE: The fate of transplanted donor tracheal
      mucosa is elucidated, and may substantially explain the mechanism of rejection
      resistance.

PMID- 17547998
TI  - Three-dimensional imaging of the pterygopalatine fossa.

PMID- 17547999
TI  - The implications of regulatory guidelines on allergen vial mixing for the
      practicing otolaryngologist.
AB  - OBJECTIVES: To introduce otolaryngologists to proposed standards regarding
      allergen vial mixing, to identify clinical implications, and to recommend efforts
      to address the issue of vial mixing standards. STUDY DESIGN AND METHODS: A policy
      review. RESULTS: The Institute of Medicine report on medical errors increased
      awareness of medication errors, spurring efforts to improve patient safety. One
      example is the United States Pharmacopoeia's (USP) Chapter 797, a standard for
      sterile medication compounding. This standard requires the use of a dedicated
      clean room, ventilation hood, air sampling, surface sampling, and formal testing
      of mixing personnel. Regulatory agencies may include allergy vial mixing under
      USP 797. Formal allergy vial mixing guidelines are presented as a standard
      created by the American Academy of Otolaryngic Allergy taskforce on allergen vial
      mixing. CONCLUSION/SIGNIFICANCE: Otolaryngologists must be involved the
      discussion regarding vial mixing standards to ensure that the standards developed
      are reasonable, safe, preserve patient access, and are based on evidence based
      medicine.

PMID- 17548000
TI  - Post-traumatic cerebrospinal fluid rhinorrhea revealing an asymptomatic pituitary
      adenoma.

PMID- 17548001
TI  - Persistent buccopharyngeal membrane.

PMID- 17548002
TI  - Brucella melitensis infection of a branchial cyst.

PMID- 17548003
TI  - Retropharyngeal bronchogenic cyst.

PMID- 17548004
TI  - Hutchinson sign and herpes zoster.

PMID- 17548006
TI  - Diaphyseal fractures of the radius and ulna in adults.
AB  - Diaphyseal fractures involving the radius and ulna, so called "both-bone" or
      "double-bone" forearm fractures are common orthopedic injuries. These injuries
      can result in significant loss of function if inadequately treated. As the upper
      extremity serves to position the hand in space, loss of forearm motion and/or
      muscle imbalance resulting from a poorly treated fracture can be particularly
      debilitating. Preservation of the anatomic relationships of the proximal and
      distal radioulnar joints as well as the interosseous space is critical to
      preserving function. This article overviews the management of diaphyseal
      fractures of the radius and ulna in adults.

PMID- 17548007
TI  - Galeazzi fractures and dislocations.
AB  - In 1934, fractures of the middle and distal third of the radius associated with
      instability of the distal radial ulnar joint (DRUJ) were described by Galeazzi.
      This type of lesion is characterized by its unstable nature and the need for open
      reduction and internal fixation to achieve a satisfactory functional outcome. A
      high index of suspicion should be maintained by the surgeon, and a thorough
      examination for instability of the DRUJ must be conducted. The marked instability
      of this fracture-dislocation complex is further enhanced by the disruption of the
      triangular fibrocartilage complex, either with or without ulna styloid fracture.
      Treatment in adults is surgical, and both bone and soft tissue injuries should be
      addressed.

PMID- 17548008
TI  - Monteggia fracture-dislocations.
AB  - Monteggia fracture-dislocations remain a relatively uncommon injury. Prompt
      recognition of this injury is imperative. The character of the ulnar fracture is
      useful in determining optimal treatment. It is imperative to look for associated
      injuries of the radial head and coronoid, which alter the management and lead to
      altered outcomes.

PMID- 17548009
TI  - Management of isolated ulnar shaft fractures.
AB  - Isolated fractures of the ulnar shaft are common forearm injuries. Although
      seemingly benign, they may be complicated by nonunion, radioulnar synostosis, and
      loss of motion. Unstable fractures are those that are displaced more than 50
      percent, angulated more than 10 degrees, or are located in the proximal third of
      the ulna. Stable fractures are managed well with forearm bracing. Unstable
      fractures are reliably treated with open reduction and internal fixation with
      compression plating.

PMID- 17548010
TI  - Radial head fractures.
AB  - Radial head fractures are the most common adult elbow fracture. Our ability to
      treat these fractures has improved with increased understanding of elbow
      biomechanics. Based on fracture type, possible treatment includes nonoperative
      management, open reduction and internal fixation, radial head resection, and
      replacement arthroplasty. Management and operative technique are discussed.

PMID- 17548011
TI  - Longitudinal radioulnar dissociation: identification and treatment of acute and
      chronic injuries.
AB  - In this article we describe the fundamental concepts that were established by
      Essex-Lopresti over 50 years ago and explore the current concepts in anatomy,
      biomechanics, diagnosis, and treatment for longitudinal radioulnar dissociation.
      Moreover, we present encouraging results for treating chronic injuries to the IOM
      achieved by bone-ligament-bone (BLB) reconstruction using a patellar tendon
      graft, giving hope for this seemingly unforgiving injury. A treatment algorithm
      is also provided to aid in the management of acute and chronic longitudinal
      radioulnar dissociation.

PMID- 17548012
TI  - Contemporary evaluation and treatment of distal radius fractures.
AB  - Distal radius fractures are among the most common fractures encountered by
      orthopedic surgeons. Because of many fracture patterns and types, it has been
      difficult to develop a comprehensive classification. Treatment options vary
      depending on injury severity and stability of the fracture reduction. Closed
      reduction and immobilization can be used for stable fractures. Common surgeries
      include pinning with and without external fixation and open reduction and
      internal fixation. Technological advances such as locking and fixed angle plates
      have made the volar approach feasible. Dorsal plating with low profile plates and
      fragment-specific techniques can be successful in treating distal radius
      fractures. Following fracture reduction and stabilization, assessment of distal
      radioulnar joint stability is essential and must be stabilized when necessary.

PMID- 17548013
TI  - Management of posttraumatic metadiaphyseal radioulnar synostosis.
AB  - Posttraumatic radioulnar synostosis results in functional loss of forearm
      rotation. Treatment preference is to excise the synostosis when associated
      fractures have healed or when the process is radiographically static.
      Interposition material is used in the region of the proximal radioulnar joint or
      when the medullary canal of the radius or ulna is breached. Irradiation is
      limited to lesions at or proximal to the radial tuberosity. Postoperative
      management includes resting splint that holds the extremity in the extremes of
      forearm rotation, and intermittent active and passive range of motion exercises.
      Anti-inflammatory medications are used only during hospitalization. Results have
      shown a good functional arc of pronosupination, and no recurrence, especially
      when the process is limited to the midforearm.

PMID- 17548014
TI  - Malunions and nonunions of the forearm.
AB  - Modern techniques allow for high rates of union in the treatment of diaphyseal
      forearm fractures. In the case of nonunion, addressing the biology and stability
      of the fracture will similarly yield high union rates, but slightly decreased
      functional outcomes. Malunion of forearm fractures typically results in loss of
      range of motion and grip strength. Restoration of the anatomical relationships of
      the forearm yields functional results. Understanding and recreating the anatomy
      of the forearm is the key to obtaining good functional outcomes.

PMID- 17548015
TI  - Management of forearm compartment syndrome.
AB  - Compartment syndrome of the forearm is a serious medical problem, and it is
      commonly associated with high-energy injuries to the upper extremity. Timely
      recognition and treatment are critical to ensuring a good outcome and avoiding
      permanent functional loss. The diagnosis is primarily based on clinical
      suspicion. Surgical intervention with fasciotomy is the mainstay of treatment.

PMID- 17548016
TI  - Initial assessment and management of complex forearm defects.
AB  - Complex trauma to the forearm often involves significant damage to or loss of
      bone, muscle, skin, tendons, and neurovascular structures. Treatment focuses on
      regaining long-term hand function, which is best achieved by combining plastic
      and orthopedic surgical expertise in a team that includes experienced upper arm
      rehabilitation therapists. The reconstruction goal is to restore a level of hand
      function that allows the patient to incorporate the injured hand back into daily
      activities. We define complex defects as those involving significant segmental
      loss of one or more tissue types. This article provides a framework by which
      these often formidable and overwhelming injuries can be approached, and discusses
      some of the surgical options used to reconstruct complex defects of the forearm.

PMID- 17548017
TI  - Locking plate technology and its applications in upper extremity fracture care.
AB  - Locking plate technology has been a major advance in fracture care. These plates
      afford a stronger construct and have been useful in cases where the bone is
      osteoporotic and unicortical fixation or distal periarticular fracture fixation
      is necessary. Disadvantages include fixed angle screw fixation and inability to
      compress at the fracture site; however, the use of a combination of compression
      and locking screws allows for both fracture compression with cortical screws and
      stronger fixation with locking screws. Future studies will refine the indications
      and overall efficacy in the use of this technology.

PMID- 17548018
TI  - Impact of the Leapfrog Group's intensive care unit physician staffing standard.
AB  - PURPOSE: The aim of this study was to describe hospital efforts to meet the
      Leapfrog Group's intensive care unit (ICU) physician staffing (IPS) standard;
      compare adopters and committers with resisters relative to perceived benefits,
      barriers and motivating factors; and examine implementation strategies. MATERIALS
      AND METHODS: Chief medical officers (CMO) and ICU directors at hospitals in 6 US
      regions were surveyed between August 2003 and January 2004. Hospital
      classifications were based on level of IPS implementation pioneer (met before
      IPS), adopter (met after IPS by 2002 Leapfrog survey), committer (not met but
      committed to December 2004 implementation), and resister (refused to adopt IPS).
      Meeting IPS included intensivist staffing, 8 hours/day 7 days/week; sole patient
      care in ICU; 95% pager response time </=5 minutes; and physicians certified in
      critical care. RESULTS: Forty-three (80%) CMOs and 42 (78%) ICU directors were
      interviewed. Adopters (100%), committers (80%), and resisters (45%) employed
      intensivists; 1 adopter (14%) met all criteria for standard. Main motivators for
      implementation were "quality of patient care" for CMO (79%) and ICU director
      (71%) adopter/committers. Incentives to implement were increasing intensivist
      authority (90% committers) and intensivist salary support (80% committers and 70%
      adopters). Main resister barriers were implementation costs (61% CMOs) and
      medical staff controversy (55% ICU directors). CONCLUSION: Most hospitals
      including half of those who publicly resisted the standard-made attempts to
      change physician staffing in their ICUs, based on the criteria outlined by the
      Leapfrog Group. Major barriers that need addressing are implementation costs and
      convincing hospital organizations and medical staff regarding the benefits of
      adopting the standard.

PMID- 17548019
TI  - Barriers to implementing the Leapfrog Group recommendations for intensivist
      physician staffing: a survey of intensive care unit directors.
AB  - PURPOSE: The Leapfrog Group, representing a consortium of health care purchasers,
      has promoted standards for intensive care unit (ICU) staffing in nonrural areas.
      The purpose of this study was to examine the perception of the Leapfrog standards
      among ICU directors and determine the potential barriers to implementing these
      standards. MATERIALS AND METHODS: We performed a telephone survey of physician
      ICU directors using a stratified random sample of hospitals in the Committee on
      Manpower for Pulmonary Critical Care Societies database. RESULTS: Seventy-two
      ICUs in 72 hospitals were surveyed. Forty-seven ICUs responded to telephone
      inquires. Of these, 21 (45%) could identify an ICU director, 20 of which answered
      questions about their own hospital's compliance. Only 5 ICU directors (25%) cited
      current compliance with the Leapfrog standard for intensivist staffing. Of the 15
      directors not in compliance, 13 were motivated to adopt the recommendations in
      the future. Loss of control, loss of income, and increased cost to hospital
      administration were cited as important barriers to implementing the
      recommendations. Increased availability of intensivists, increased funds from
      hospital administrators, and assistance from government and third parties were
      viewed as important potential solutions to these barriers. CONCLUSIONS: Numerous
      barriers exist to implementing the Leapfrog recommendations for intensivist
      staffing, not the least of which is the lack of an ICU director in many
      hospitals. Better strategies are needed to overcome these barriers before the
      widespread adoption of an intensivist care model similar to Leapfrog is feasible.

PMID- 17548020
TI  - How qualitative research can contribute to research in the intensive care unit.
AB  - A qualitative research design can provide unique contributions to research in the
      intensive care unit. Qualitative research includes the entire process of
      research: the methodology (conceptualization of the research question, choosing
      the appropriate qualitative strategy, designing the protocol), methods
      (conducting the research using qualitative methods within the chosen qualitative
      strategy, analysis of the data, verification of the findings), and writing the
      narrative. The researcher is the instrument and the data are the participants'
      words and experiences that are collected and coded to present experiences,
      discover themes, or build theories. A number of strategies are available to
      conduct qualitative research and include grounded theory, phenomenology, case
      study, and ethnography. Qualitative methods can be used to understand complex
      phenomena that do not lend themselves to quantitative methods of formal
      hypothesis testing. Qualitative research may be used to gain insights about
      organizational and cultural issues within the intensive care unit and to improve
      our understanding of social interaction and processes of health care delivery. In
      this article, we outline the rationale for, and approaches to, using qualitative
      research to inform critical care issues. We provide an overview of qualitative
      methods available and how they can be used alone or in concert with quantitative
      methods. To illustrate how our understanding of social phenomena such as patient
      safety and behavior change has been enhanced we use recent qualitative studies in
      acute care medicine.

PMID- 17548021
TI  - Lowering of glucose in critical care: a randomized pilot trial.
AB  - BACKGROUND: Similar to cardiac surgery patients, medical-surgical critically ill
      patients may benefit from intensive insulin therapy. The objectives of this pilot
      trial were to evaluate the feasibility of a randomized trial of intensive insulin
      therapy with respect to (a) achieving target glucose values in the 2 ranges of 5
      to 7 and 8 to 10 mmol/L and (b) uncovering problems with the protocol in
      anticipation of a larger trial. SETTING: The trial was conducted in a 15-bed
      medical-surgical university-affiliated intensive care unit (ICU). METHODS: We
      included patients older than 18 years, expected to be in ICU for more than 72
      hours, with a glucose value of more than 10 mmol/L within 48 hours of ICU
      admission. Exclusion criteria were diabetic ketoacidosis, severe hepatic failure
      or hepatic resection, pancreatitis, glucose of less than 2.2 mmol/L on admission
      to hospital, insulin infusion on admission to ICU, planned withdrawal of life
      support, and inability to obtain informed consent. Patients underwent concealed
      random allocation to a target glucose range of 5 to 7 or 8 to 10 mmol/L using
      pretested algorithms of insulin infusions. Dedicated glucometer measurement of
      arterial glucose values was calibrated daily to values measured in the
      laboratory. RESULTS: We enrolled 20 patients with a mean (SD) Acute Physiology
      and Chronic Health Evaluation (APACHE) II score of 32 (10.2); 14 were insulin
      dependent pre-ICU, and all were medical admissions. Mean glucose values were
      different in the 2 groups (7.1 +/- 2.6 vs 9.4 +/- 2.1 mmol/L, P < .001). Although
      the intensive insulin therapy group had more glucose measurements performed than
      the control group, a similar proportion of values were within the target range
      (682 [42.4%] of 1607 values in the 5- to 7-mmol/L range; 250 [38.7%] of 660
      values in the 8- to 10-mmol/L range, P = .35). Glucose values of less than 2.5
      mmol/L developed 7 times in 5 patients, 4 of whom were in the intensive insulin
      therapy group; however, no adverse consequences were documented. As expected,
      there were no differences in clinically important outcomes. CONCLUSIONS: In this
      pilot trial of ICU patients with high illness severity, glucose values were in
      the 2 target ranges only 40% of the time, using well-accepted initiation and
      maintenance insulin infusion algorithms. A large randomized trial of glycemic
      control is feasible in this population to examine clinically important outcomes,
      but will require refined insulin algorithms and more comprehensive behavior
      change strategies to achieve target values.

PMID- 17548023
TI  - Analysis of physiologic alterations in intensive care unit patients and their
      relationship with mortality.
AB  - PURPOSE: To analyze patient physiologic alterations (events) and multiple organ
      failure during intensive care unit (ICU) stay and examine their relationship with
      ICU mortality. MATERIAL AND METHODS: A total of 17598 consecutive patients were
      studied for 10 months (1997-1998) in 55 European ICUs (EURICUS-II). Hourly data
      were collected on critical and noncritical systolic blood pressure, heart rate,
      oxygen saturation, and urinary events throughout ICU stay. Sepsis-related Organ
      Failure Assessment (SOFA) score was collected daily (6409 patients). RESULTS:
      SAPS-II was 31.2 +/- 18.4 and ICU mortality 13.9%. There were 3.4 +/- 9.2
      noncritical (duration, 3.9 +/- 11.4 hours) and 2 +/- 7.5 critical (3.8 +/- 13.1
      hours) systolic blood pressure events per patient. Heart rate, oxygen saturation,
      and urinary events had similar values. Nonsurvivors had significantly more and
      longer physiologic alterations vs survivors. Mortality was significantly related
      to mean daily duration of events and mean and maximum daily SOFA. Discrimination
      capacity to predict ICU mortality was measured using various models: with SAPS
      II, area under the receiver operating characteristic curve was 0.80; with APACHE
      III-classified diagnosis added, 0.84; with mean duration of events/ICU day, 0.91;
      and with mean and maximum SOFA scores, 0.95. CONCLUSION: Routinely gathered ICU
      data on physiologic variables and multiple organ failure can offer considerable
      complementary information not provided by usual mortality prediction systems; and
      their weight in daily care policy decisions may need to be revisited.

PMID- 17548024
TI  - Early evolution of arterial oxygenation in severe community-acquired pneumonia: a
      prospective observational study.
AB  - PURPOSE: Acute respiratory failure requiring mechanical ventilation in severe
      community-acquired pneumonia has been shown to be a significant negative
      prognostic factor. We analyzed the early evolution of the Pao(2)/Fio(2) ratio and
      evaluated its clinical value as an outcome predictor. MATERIALS AND METHODS: This
      is a prospective study conducted in a tertiary referral hospital. In 62 adult
      patients requiring early mechanical ventilation due to severe community-acquired
      pneumonia, we measured serial changes in Pao(2)/Fio(2) ratio and other clinical
      variables within the first 48 hours of mechanical ventilation and compared the
      difference between survivors and nonsurvivors. RESULTS: The initial Pao(2)/Fio(2)
      ratio was lower in nonsurvivors (n = 27) than in survivors (n = 35) (158.0 +/-
      55.8 vs 117.9 +/- 50.6, P = .025). Over the next 48 hours, the ratio increased
      significantly in survivors but not in nonsurvivors (analysis of variance, P <
      .001). An increase in Pao(2)/Fio(2) ratio greater than 56 mm Hg had a sensitivity
      of 75% and a specificity of 81% of survival. A definite causative pathogen was
      identified in 36 patients (58%) and the 3 most commonly isolated pathogens were
      Streptococcus pneumoniae, Staphylococcus aureus, and Klebsiella pneumoniae. Ten
      patients received inadequate initial empirical antimicrobial therapy, in which
      the Pao(2)/Fio(2) ratio change was significantly less than those who were
      adequately treated (analysis of variance, P < .001). Mortality was much higher
      (86% [6/7]) in patients who received inadequate antibiotics and where
      Pao(2)/Fio(2) ratio change was less than 56 mm Hg. On multivariate analysis,
      trend changes in Pao(2)/Fio(2) ratio over 48 hours, shock, and Acute Physiology
      and Chronic Health Evaluation II score were documented to be independent
      predictors of mortality. CONCLUSIONS: A progressive improvement of Pao(2)/Fio(2)
      ratio during the first 48 hours of mechanical ventilation indicates favorable
      outcome. Serial measurement of this ratio should be considered in decision making
      for therapeutic strategy.

PMID- 17548025
TI  - Mobile communication devices causing interference in invasive and noninvasive
      ventilators.
AB  - PURPOSE: The aim of this study was to assess if common mobile communication
      systems would cause significant interference on mechanical ventilation devices
      and at what distances would such interference occur. MATERIALS AND METHODS: We
      tested all the invasive and noninvasive ventilatory devices used within our
      region. This consisted of 2 adult mechanical ventilators, 1 portable ventilator,
      2 pediatric ventilators, and 2 noninvasive positive pressure ventilatory devices.
      We operated the mobile devices from the 2 cellular communication systems
      (digital) and 1 2-way radio system used in our province at varying distances from
      the ventilators and looked at any interference they created. We tested the 2-way
      radio system, which had a fixed operation power output of 3.0 watts, the Global
      Systems for Mobile Communication cellular system, which had a maximum power
      output of 2.0 watts and the Time Division Multiple Access cellular system, which
      had a maximum power output of 0.2 watts on our ventilators. The ventilators were
      ventilating a plastic lung at fixed settings. The mobile communication devices
      were tested at varying distances starting at zero meter from the ventilator and
      in all operation modes. RESULTS: The 2-way radio caused the most interference on
      some of the ventilators, but the maximum distance of interference was 1.0 m. The
      Global Systems for Mobile Communication system caused significant interference
      only at 0 m and minor interference at 0.5 m on only 1 ventilator. The Time
      Division Multiple Access system caused no interference at all. Significant
      interference consisted of a dramatic rise and fluctuation of the respiratory
      rate, pressure, and positive end-expiratory pressure of the ventilators with no
      normalization when the mobile device was removed. CONCLUSIONS: From our
      experiment on our ventilators with the communication systems used in our
      province, we conclude that mobile communication devices such as cellular phones
      and 2-way radios are safe and cause no interference unless operated at very close
      distances of less than 1 meter.

PMID- 17548026
TI  - International integrated database for the evaluation of severe sepsis and
      drotrecogin alfa (activated) therapy: 28-day survival and safety.
AB  - PURPOSE: To enhance the understanding of severe sepsis, a database of patients
      from multiple clinical trials spanning a 6-year period was constructed. Initial
      analyses evaluated the 28-day survival in the placebo group and further assessed
      the treatment effect of drotrecogin alfa (activated) (DrotAA). METHODS: Five
      severe sepsis studies with similar entry criteria were combined, and baseline
      characteristics and 28-day mortality were evaluated (4459 severe sepsis patients;
      placebo, n = 1231; DrotAA, n = 3228). An integrated data analysis with propensity
      score adjustment was performed. Twenty-one variables selected by stepwise
      logistic regression were included in a propensity score of differences between
      the 2 groups of patients. RESULTS: Over the 6-year period of these trials, there
      was no change in placebo mortality rates overall (P = .67), nor in subgroups of
      Acute Physiology and Chronic Health Evaluation score >/=25 (P = .73) or multiple
      organ dysfunction (P = .38). The adjusted relative hazard risk for DrotAA
      patients was 0.84 (95% confidence interval, 0.73-0.95; P = .007). Serious
      bleeding (0.8% in placebo vs 3.5% in DrotAA, P < .0001) was increased during the
      DrotAA infusion period. CONCLUSIONS: Initial analyses indicate that placebo
      mortality remained unchanged over a recent 6-year period. These analyses also
      further substantiate that treatment with DrotAA is associated with improved
      survival.

PMID- 17548027
TI  - Long-term outcomes in patients requiring stay of more than 48 hours in the
      intensive care unit following coronary bypass surgery.
AB  - BACKGROUND: The primary objective of this study was to determine the long-term
      outcomes of all patients requiring prolonged intensive care unit (ICU) stay
      following coronary bypass surgery (CABG) surgery. METHODS: All patients
      undergoing CABG surgery between 1998 and 2002 were reviewed. Prolonged ICU stay
      was defined as more than 48 hours. Short-term (in-hospital) and long-term
      (postdischarge) outcomes were evaluated using available databases. RESULTS: Of
      3139 patients who underwent CABG surgery, 598 required an ICU stay of more than
      48 hours (19%). The in-hospital mortality for patients requiring prolonged ICU
      stay was 10.0% as compared with 1.2% for the remainder of patients (P < .0001).
      The median length of hospitalization for patients requiring prolonged stay was 11
      days (IQR 7-18) as compared to 6 days (IQR 5-7). The median follow-up of patients
      who survived to discharge was 31 months with a 100% follow-up. Using Cox
      proportional hazard ratio, patients who required a prolonged ICU stay were found
      to have a significant lower survival and freedom from cardiac readmission to the
      hospital. Prolonged ICU stay was an independent predictor of composite outcome
      (death + readmission) with a hazard ratio of 1.8 (1.5-2.1). CONCLUSIONS:
      Prolonged ICU stay following CABG resulted in increased early and late mortality
      and lower freedom from readmission to hospital for cardiac reasons.

PMID- 17548028
TI  - Intensive care unit cultures and end-of-life decision making.
AB  - PURPOSE: Prior researchers studying end-of-life decision making (EOLDM) in
      intensive care units (ICUs) often have collected data retrospectively and
      aggregated data across units. There has been little research, however, about how
      cultures differ among ICUs. This research was designed to study limitation of
      treatment decision making in real time and to evaluate similarities and
      differences in the cultural contexts of 4 ICUs and the relationship of those
      contexts to EOLDM. MATERIALS AND METHODS: Ethnographic field work took place in 4
      adult ICUs in a tertiary care hospital. Participants were health care providers
      (eg, physicians, nurses, and social workers), patients, and their family members.
      Participant observation and interviews took place 5 days a week for 7 months in
      each unit. RESULTS: The ICUs were not monolithic. There were similarities, but
      important differences in EOLDM were identified in formal and informal rules,
      meaning and uses of technology, physician roles and relationships, processes such
      as unit rounds, and timing of initiation of EOLDM. CONCLUSIONS: As interventions
      to improve EOLDM are developed, it will be important to understand how they may
      interact with unit cultures. Attempting to develop one intervention to be used in
      all ICUs is unlikely to be successful.

PMID- 17548029
TI  - Challenges and rewards on the road to translational systems biology in acute
      illness: four case reports from interdisciplinary teams.
AB  - INTRODUCTION: Translational systems biology approaches can be distinguished from
      mainstream systems biology in that their goal is to drive novel therapies and
      streamline clinical trials in critical illness. One systems biology approach,
      dynamic mathematical modeling (DMM), is increasingly used in dealing with the
      complexity of the inflammatory response and organ dysfunction. The use of DMM
      often requires a broadening of research methods and a multidisciplinary team
      approach that includes bioscientists, mathematicians, engineers, and computer
      scientists. However, the development of these groups must overcome domain
      specific barriers to communication and understanding. METHODS: We present 4 case
      studies of successful translational, interdisciplinary systems biology efforts,
      which differ by organizational level from an individual to an entire research
      community. RESULTS: Case 1 is a single investigator involved in DMM of the acute
      inflammatory response at Cook County Hospital, in which extensive translational
      progress was made using agent-based models of inflammation and organ damage. Case
      2 is a community-level effort from the University of Witten-Herdecke in Cologne,
      whose efforts have led to the formation of the Society for Complexity in Acute
      Illness. Case 3 is an institution-based group, the Biosystems Group at the
      University of California, San Francisco, whose work has included a focus on a
      common lexicon for DMM. Case 4 is an institution-based, transdisciplinary
      research group (the Center for Inflammation and Regenerative Modeling at the
      University of Pittsburgh), whose modeling work has led to internal education
      efforts, grant support, and commercialization. CONCLUSION: A transdisciplinary
      approach, which involves team interaction in an iterative fashion to address
      ambiguity and is supported by educational initiatives, is likely to be necessary
      for DMM in acute illness. Communitywide organizations such as the Society of
      Complexity in Acute Illness must strive to facilitate the implementation of DMM
      in sepsis/trauma research into the research community as a whole.

PMID- 17548031
TI  - Neuroendocrine carcinomas (carcinoid, atypical carcinoid, small cell carcinoma,
      and large cell neuroendocrine carcinoma): current concepts.
AB  - Neuroendocrine carcinomas are ubiquitous neoplasms that may occur anywhere in the
      human body. A unifying concept regarding the classification of these tumors has
      been controversial. Although most neuroendocrine neoplasms occur in the
      gastrointestinal tract, current concepts regarding classification and
      nomenclature are being driven by studies of thoracic tumors. One issue that has
      been put forward to keep separate nomenclatures for these tumors in different
      organ systems is the different clinical behavior of these neoplasms in different
      systems. The most important aspect regarding this group of tumors is the fact
      that they should be considered neoplasms capable of local recurrence and distant
      metastasis. Close clinical correlation and appropriate treatment are important to
      improve the survival rate in this group of patients.

PMID- 17548032
TI  - Imaging of neuroendocrine tumors.
AB  - Neuroendocrine tumors may arise from a wide range of organs and may occur in
      various locations in the body. They include carcinoid tumors, paragangliomas
      (pheochromocytomas), medullary thyroid carcinomas, and islet cell tumors of the
      pancreas. In this article the authors focus on the more common tumors with
      origins primarily in the abdomen, namely carcinoid, paraganglioma, and pancreatic
      islet cell tumors. Imaging assists in delineating the sites and extent of
      disease, in preoperative planning for resection of the primary tumor and
      metastatic disease, and in follow-up. Discussion is restricted to the main
      imaging modalities used in these tumors: cross-sectional imaging, namely CT and
      MRI, and nuclear medicine studies.

PMID- 17548033
TI  - Clinical presentation and management of carcinoid tumors.
AB  - The generally indolent nature of neuroendocrine tumors is an advantage in the
      management of patients who have localized disease, and surgery alone is often
      curative. This same property presents a challenge in the treatment of patients
      who have metastatic disease, in whom standard cytotoxic chemotherapy has a
      limited benefit. In such patients, the use of somatostatin analogs, interferon,
      and the treatment of hepatic metastases may provide effective palliation. The
      highly vascular nature of carcinoid tumors has led to the investigation of
      antiangiogenic agents in this setting. Preliminary reports of activity associated
      with agents targeting the vascular endothelial growth factor pathway suggest that
      such strategies may play a role in the future treatment of patients who have this
      disease.

PMID- 17548034
TI  - Islet cell carcinoma: neuroendocrine tumors of the pancreas and periampullary
      region.
AB  - Most patients who have islet cell tumors, except those who have insulinomas,
      present with locally advanced or metastatic disease. In contrast with patients
      who have adenocarcinoma of the pancreas, those who have islet cell carcinomas can
      achieve long-term survival even if their disease is advanced. Liver-directed
      therapies, somatostatin analogs, and interferon are not curative but can be used
      to relieve tumor-associated symptoms. Similarly, palliative chemotherapy has been
      used with limited success. Advances in our understanding of the molecular
      mechanisms underlying tumor progression have translated into intense interest in
      biologically based strategies to treat this disease.

PMID- 17548035
TI  - Medullary thyroid carcinoma.
AB  - Medullary thyroid carcinoma is a neuroendocrine tumor derived from the C cells of
      the thyroid gland and accounts for approximately 5% of all thyroid carcinomas.
      Approximately 30% of the cases are associated with an autosomal dominant syndrome
      called multiple endocrine neoplasia type 2, and the identification of these
      individuals is important because affected family members may benefit from an
      early diagnosis. The treatment of this disease is predominantly surgical, and the
      impact of radiotherapy and chemotherapy is limited. The identification of the
      associated molecular events has lead to the development of specific molecular
      targeted agents that may change the way this disease is treated in the near
      future.

PMID- 17548036
TI  - Adrenal cortical carcinoma--review of current knowledge and treatment practices.
AB  - Adrenal cortical carcinoma is a rare endocrine malignancy with a poor long-term
      prognosis. Accurate diagnosis and preoperative evaluation of the patient
      presenting with an adrenal mass maximize the opportunity for optimal treatment
      planning. Surgery still offers the best chance for cure. Despite curability with
      complete surgical resection, the rate of recurrence is unacceptably high. In
      metastatic or recurrent disease, systemic treatment options are limited to
      chemotherapy with or without mitotane. Therapeutic options are often outdated and
      associated with significant toxicities. A multidisciplinary approach has the best
      chance for offering optimized management of this lethal disease. Improved
      understanding of the molecular pathogenesis of this rare malignancy will lead to
      advancement in the available therapies that may improve this outcome.

PMID- 17548037
TI  - Pheochromocytoma: advances in genetics, diagnosis, localization, and treatment.
AB  - Pheochromocytomas are rare, catecholamine-secreting tumors arising most
      frequently in the chromaffin cells of the adrenal glands. Recent studies have
      suggested that genetic mutations are more frequent than previously appreciated in
      patients with these lesions. Advances continue to be made not only in the genetic
      evaluation of these patients but also in the biochemical confirmation and tumor
      localization. Surgery remains the definitive treatment, and advances in
      laparoscopic techniques as well as cortical-sparing procedures have reduced the
      morbidity associated with tumor resection.

PMID- 17548038
TI  - Merkel cell carcinomas.
AB  - Merkel cell carcinoma (MCC) is a rare and extremely aggressive skin cancer that
      arises from primary neural cells. It presents most commonly in the elderly and
      immunocompromised patients. Pathologically, MCC should be distinguished from
      extrapulmonary small cell lung cancer or metastatic small cell lung cancer or a
      small cell variant of melanoma. The prognosis is based largely on the stage of
      disease at the time of presentation. Therapeutic options for MCC include wide
      resection with or without adjuvant radiotherapy or chemotherapy. Novel therapies
      based on the understanding of the molecular aspects of MCC are currently being
      explored.

PMID- 17548039
TI  - Liver-directed therapies for metastatic neuroendocrine tumors.
AB  - Neuroendocrine tumors, despite being indolent, frequently cause significant
      morbidity and mortality from hepatic metastatic lesions. It is possible to
      directly target these liver lesions with embolization/chemoembolization,
      radiofrequency ablation, or other therapies. The observational studies that exist
      seem to indicate a prolongation of survival. Liver-directed therapies are also
      able to decrease symptoms in most patients. The value of these therapeutic
      interventions therefore lies mainly in their palliative capabilities. Coupled
      with aggressive use of octreotide, local ablative techniques may frequently
      control symptoms of hormone excess and tumor bulk. Because of the possible
      adverse effects of these interventions, however, careful patient selection is
      essential to minimize the morbidity and mortality of the procedures.

PMID- 17548040
TI  - Treatment of patients who have endocrine gastroenteropancreatic tumors with
      radiolabeled somatostatin analogues.
AB  - Treatment with radiolabeled somatostatin analogs is a promising new tool in the
      management of patients who have inoperable or metastasized endocrine tumors.
      Symptomatic improvement may occur with all (111)In-, (90)Y-, or (177)Lu-labeled
      somatostatin analogs that have been used for peptide receptor radionuclide
      therapy. The results that were obtained with [(90)Y-DOTA degrees
      ,Tyr(3)]octreotide and [(177)Lu-DOTA degrees ,Tyr(3)]octreotate are encouraging
      in tumor regression. Also, if kidney-protective agents are used, the side effects
      of this therapy are few and mild. These data compare favorably with the limited
      number of alternative treatment approaches.

PMID- 17548041
TI  - Molecular targeted therapy for neuroendocrine tumors.
AB  - Although endocrine tumors are often slow growing, most can be life threatening
      and are considered resistant to conventional cytotoxic chemotherapy. The recent
      emergence of molecularly targeted therapy in oncology has brought renewed
      interest in the development of novel agents for this rare group of diseases.
      Preliminary results from phase II studies have shown promising results for VEGF
      and mTOR inhibitors in carcinoid and islet cell carcinoma and RET inhibitors in
      medullary thyroid carcinoma. Large confirmatory studies are planned.

PMID- 17548042
TI  - Interleukin-1 is not essential for expression of inducible NOS in hepatocytes
      induced by lipopolysaccharide in vivo.
AB  - Interleukin (IL)-1 and tumor necrotic factor alpha (TNFalpha) are pivotal in the
      pathogenesis of endotoxemia. In spite of the in vitro finding that IL-1beta, but
      not TNFalpha, can induce iNOS mRNA and NO production as a single stimulus in
      hepatocytes in primary culture, the involvement of IL-1 in iNOS induction in the
      liver has been less clear in vivo. To address this, we challenged IL-1alpha/beta
      double-knockout (IL-1alpha/beta(-/-)) and TNFalpha(-/-) mice with
      lipopolysaccharide (LPS). As compared with wild-type mice, the increases in the
      plasma NO level measured as nitrite and nitrate and hepatic iNOS were
      significantly reduced in IL-1alpha/beta(-/-) and TNFalpha(-/-) mice 8 and 12h
      after the LPS challenge. In the wild-type mice, iNOS protein was first detected
      in Kupffer cells around the portal vein 2h after LPS challenge; and then it
      spread to hepatocytes throughout the intralobular region of the liver by 8h.
      Although the expression of iNOS protein was detected in Kupffer cells of both IL
      1alpha/beta(-/-) and TNFalpha(-/-) mice, its level was moderate in hepatocytes of
      IL-1alpha/beta(-/-) mice, but negligible in those of TNFalpha(-/-) mice, 8h after
      LPS challenge. Concomitant with the expression of iNOS protein in the liver, Toll
      like receptor 4, the signaling receptor for LPS, was expressed in hepatocytes of
      wild-type and IL-1alpha/beta(-/-) mice, but not of TNFalpha(-/-) mice. These
      results demonstrate that the expression of Toll-like receptor 4 is well
      correlated with that of iNOS protein in hepatocytes in vivo after LPS challenge
      and that IL-1 is not essential for the induction of iNOS in hepatocytes in vivo.

PMID- 17548043
TI  - Quantitation of aggregates in therapeutic proteins using sedimentation velocity
      analytical ultracentrifugation: practical considerations that affect precision
      and accuracy.
AB  - Aggregation is a major degradation pathway that needs to be characterized and
      controlled during the development of protein pharmaceuticals. Analytical
      ultracentrifugation-sedimentation velocity (AUC-SV) is emerging as an important
      orthogonal tool to size exclusion chromatography to quantitate aggregates.
      However, the precision and accuracy of modern AUC-SV and the experimental
      variables that influence these two performance parameters need to be better
      understood and controlled. To understand the impact of experimental and data
      analysis variables on the precision, aggregate content in monoclonal antibody
      preparations was measured by AUC-SV and analyzed by the software program Sedfit.
      Accuracy and limit of detection were evaluated by spiking a known quantity of a
      sample enriched in aggregate fraction. The results suggest experimental and data
      analysis approaches that improve precision and accuracy of aggregate quantitation
      by AUC-SV. Both precision and accuracy were found to be highly dependent on the
      quality of the centerpieces as assessed by microscopic examination. The level of
      precision for quantitating aggregates was found to be approximately +/-0.3 to
      0.7% over the aggregate content range of approximately 0.6 to 67%. Accuracy, as
      indicated by approximately 80 to 90% spiked recovery, could be achieved down to
      aggregate levels as low as approximately 1.5%, whereas the limits of detection
      and quantitation appear to be approximately 0.2 and 0.6%, respectively.

PMID- 17548044
TI  - A capillary electrophoresis method to assay catalytic activity of botulinum
      neurotoxin serotypes: implications for substrate specificity.
AB  - The potent botulinum neurotoxin inhibits neurotransmitter release at cholinergic
      nerve terminals, causing a descending flaccid paralysis characteristic of the
      disease botulism. The currently expanding medical use of the neurotoxin to treat
      several disorders, as well as the potential misuse of the neurotoxin as an agent
      in biowarfare, has made understanding of the nature of the toxin's catalytic
      activity and development of inhibitors critical. To study the catalytic activity
      of botulinum neurotoxin more thoroughly and characterize potential inhibitors, we
      have developed a capillary electrophoresis method to measure catalytic activity
      of different serotypes of botulinum neurotoxin using peptides derived from the
      native substrates. This assay requires only a minute amount of sample (25 nl), is
      relatively rapid (15 min/sample), and allows the determination of enzyme kinetic
      constants for a more sophisticated characterization of inhibitors and neurotoxin
      catalytic activity. Using this method, we can measure activity of five of the
      seven serotypes of botulinum neurotoxin (A, B, E, F, and G) with two peptide
      substrates. Botulinum neurotoxin serotypes C and D did not cleave our peptides,
      lending insight into potential substrate requirements among the serotypes.

PMID- 17548045
TI  - Fluorescent substrates for the proteinases ADAM17, ADAM10, ADAM8, and ADAM12
      useful for high-throughput inhibitor screening.
AB  - In this paper we describe novel fluorescent substrates for the human ADAM family
      members ADAM17, ADAM10, ADAM8, and ADAM12 that have good specificity constants
      and are useful for high-throughput screening of inhibitors. The fluorescence
      resonance energy transfer substrates contain a 4-(4
      dimethylaminophenylazo)benzoyl and 5-carboxyfluorescein (Dabcyl/Fam) pair and are
      based on known cleavage sequences in precursor tumor necrosis factor-alpha (TNF
      alpha) and CD23. The precursor TNF-alpha-based substrate, Dabcyl-Leu-Ala-Gln-Ala
      Homophe-Arg-Ser-Lys(Fam)-NH2, is a good substrate for all the ADAMs tested,
      including ADAM12 for which there is no reported fluorescent substrate. The CD23
      based substrate, Dabcyl-His-Gly-Asp-Gln-Met-Ala-Gln-Lys-Ser-Lys(Fam)-NH2, is more
      selective, being hydrolyzed efficiently only by ADAM8 and ADAM10. The substrates
      were used to obtain inhibition constants for four inhibitors that are commonly
      used in shedding assays: TMI-1, GM6001, GW9471, and TAPI-2. The Wyeth Aerst
      compound, TMI-1, is a potent inhibitor against all of the ADAMs tested and is
      slow binding against ADAM17.

PMID- 17548046
TI  - N-alkanamines as substrates to probe the hydrophobic region of bovine serum amine
      oxidase active site: a kinetic and spectroscopic study.
AB  - Kinetic and spectroscopic studies were carried out to study the role of
      hydrophobic effect on the activity of bovine serum amine oxidase (BSAO).
      Increasing the chain length of the substrates (linear aliphatic primary
      monoamines), the affinity for the active site increases while the catalytic
      constant decreases in accordance with a relative low value of dielectric constant
      (about 10) estimated for the microenvironment of BSAO active site using a
      fluorescent probe sensitive to solvent polarity. The aliphatic chain of 1
      aminononane induces a shift in the pK(a) of the product Schiff base, the
      hydrolysis of which appears to be a rate-determining step of the reaction.
      Furthermore, circular dichroism studies highlighted the "flexibility" of BSAO
      secondary structure that can explain the wide substrate specificity of this
      enzyme. These results should be useful to elucidate the substrate/inhibitor
      preferences of CuAOs, in particular of the human enzyme.

PMID- 17548047
TI  - Mitochondrial thioredoxin-2/peroxiredoxin-3 system functions in parallel with
      mitochondrial GSH system in protection against oxidative stress.
AB  - A dominant-negative, active-site mutant (C93S-Trx2) of mitochondrial thioredoxin
      2 (Trx2) was expressed in cells to study the function of the thioredoxin system
      in protection against mitochondrial oxidative stress. C93S-Trx2 was detected as a
      disulfide with mitochondrial peroxiredoxin-3 (Prx3) but not peroxiredoxin-5
      (Prx5). C93S-Trx2 enhanced sensitivity to cell death induced by tert
      butylhydroperoxide or by tumor necrosis factor-alpha (TNF-alpha). In cells
      treated with buthionine sulfoximine (BSO) to deplete glutathione (GSH),
      endogenous Trx2 was oxidized, C93S-Trx2 potentiated toxicity, and overexpression
      of Trx2 protected against toxicity. Thus, the results show that Trx2 interacts
      with Prx3 in vivo and that the Trx2/Prx3 system functions in parallel with the
      GSH system to protect mitochondria from oxidative stress. The additive protection
      by Trx2 and GSH shows that Trx2 and GSH systems are both functionally important
      at low oxidative stress conditions.

PMID- 17548048
TI  - Information processing biases in spider phobia: application of the Stroop and
      "White Noise" Paradigm.
AB  - The present study examines attentional and implicit memory biases in spider
      phobic and nonphobic participants. The results showed that spider phobics
      demonstrated increased interference for neutral, negative, and spider-relevant
      words on a computerized Stroop task. However, no group differences emerged when
      adjusting for differences in color-naming speed. Prior exposure to a dead spider
      did result in higher overall Stroop interference in spider phobics and this
      appeared to be mostly pronounced for spider-relevant words. Implicit memory bias
      for threat was examined with a noise judgment task. Participants first heard
      neutral and spider-relevant sentences and implicit memory for these sentences was
      evaluated by having participants rate the volume of noise accompanying the
      presentation of old sentences intermixed with new sentences. An implicit memory
      bias is indicated if participants rate noise accompanying old sentences as less
      loud than noise accompanying new sentences. No evidence was found for an implicit
      memory bias in spider phobics. These findings are discussed in relation to the
      role of information processing biases in spider phobia.

PMID- 17548049
TI  - Interoceptive fear conditioning as a learning model of panic disorder: an
      experimental evaluation using 20% CO(2)-enriched air in a non-clinical sample.
AB  - Despite the role afforded interoceptive fear conditioning in etiologic accounts
      of panic disorder, there are no good experimental demonstrations of such learning
      in humans. The aim of the present study was to evaluate the interoceptive
      conditioning account using 20% carbon dioxide (CO(2))-enriched air as an
      interoceptive conditioned stimulus (CS) (i.e., physiologically inert 5-s
      exposures) and unconditioned stimulus (US) (i.e., physiologically prepotent 15-s
      exposures). Healthy participants (N=42) were randomly assigned to one of three
      conditions: a CS-only, contingent CS-US pairings, or unpaired/non-contingent CS
      and US presentations. Electrodermal and self-report (e.g., distress, fear) served
      as indices of conditioned emotional responding. Results showed greater magnitude
      electrodermal and evaluative fear conditioning in the paired relative to the CS
      only condition. The explicitly unpaired condition showed even greater
      electrodermal and evaluative responding during acquisition, and marked resistance
      to extinction. The latter results are consistent with the possibility that the
      unpaired procedure constituted a partial reinforcement procedure in which CO(2)
      onset was paired with more extended CO(2) exposure on 50% of the trials. Overall,
      the findings are consistent with contemporary learning theory accounts of panic.

PMID- 17548050
TI  - Tyk2 mediates effects of urokinase on human vascular smooth muscle cell growth.
AB  - The urokinase (uPA)/uPA receptor (uPAR) system plays a role in the response of
      the vessel wall to injury, presumably by modulating vascular smooth muscle cell
      (VSMC) functional behaviour. The Jak/Stat signaling pathway has been implicated
      to mediate the uPA/uPAR-directed cell migration and proliferation in VSMC. We
      have therefore investigated the underlying molecular mechanisms, which remained
      not completely understood. In particular, we aimed at identification of the
      kinase involved in the signaling cascade leading to Stat1 phosphorylation by uPA
      and its impact on VSMC growth. We performed expression in VSMC of kinase
      deficient mutant forms of the Janus kinases Jak1 and Tyk2 and used different cell
      culture models imitating the response to vascular injury. We provide evidence
      that Tyk2, but not Jak1, mediates uPA-induced Stat1 phosphorylation and VSMC
      growth inhibition and suggest a novel function for Tyk2 as an important modulator
      of the uPA-directed VSMC functional behaviour at the place of injury.

PMID- 17548051
TI  - Factors associated with a purine-rich exonic splicing enhancer sequence in
      Xenopus oocyte nucleus.
AB  - Purine-rich exonic splicing enhancers (ESEs) stimulate splicing of the adjacent
      introns with suboptimal splice sites. To elucidate the mechanism regarding ESEs,
      factors specifically associated with ESEs in HeLa cell nuclear extracts were
      previously investigated, and shown to include SR (serine/arginine-rich) proteins.
      However, factors associated with ESEs in vivo have not yet been explored. Here we
      show that a GAA repeat RNA sequence, a typical ESE, is associated in Xenopus
      oocyte nuclei with at least one SR protein, SF2/ASF, as was expected. Moreover,
      components of SF3a/b complexes, U2 snRNA, and U2AF(65) were also found to be
      associated with the ESE in the nucleus. Since SF3a/b complexes are the
      constituents of the 17S U2 snRNP, these results suggest that the 17S U2 snRNP is
      associated with the ESE in the nucleus, probably through bridging interactions of
      U2AF and SR proteins. The identified factors may represent a functional splicing
      enhancer complex in vivo.

PMID- 17548052
TI  - Essential role of NKCC1 in NGF-induced neurite outgrowth.
AB  - The Na(+)/K(+)/2Cl(-) cotransporter (NKCC) mediates electroneutral transport of
      2Cl(-) coupled with Na(+) and K(+) across the plasma membrane, and plays crucial
      roles in Cl(-) uptake into the cells, homeostasis of cellular Cl(-), and cell
      volume regulation. However, we have very limited information on the roles of ion
      transporters in neurite outgrowth in neuronal cells. In the present study, we
      report the role of NKCC1 (an isoform of NKCC) in NGF-induced neurite outgrowth of
      rat pheochromocytoma PC12D cells. The expression level of NKCC1 protein was
      increased by NGF treatment. Knock-down of NKCC1 by RNA interference (RNAi)
      drastically diminished the NGF-induced neurite outgrowth. Transfection of
      enhanced green fluorescent protein (EGFP)-tagged rat NKCC1 into cells for
      clarification of intracellular localization of NKCC1 revealed that the EGFP
      rNKCC1 was mainly localized in the plasma membrane at growth cone during neurite
      outgrowth. These observations suggest that NKCC1 plays a fundamental role in NGF
      induced neurite outgrowth of PC12D cells.

PMID- 17548053
TI  - Identification and characterization of a novel and functional murine Pin1
      isoform.
AB  - Pin1, a phosphorylation-dependent peptidyl-prolyl cis/trans isomerase (PPIase),
      regulates the activity of a number of cell cycle regulators, transcription
      factors, and microtubule-associated tau. Aberrant expression of Pin1 is
      implicated in carcinogenesis and neurodegenerative diseases. Yet, there are
      discrepancies regarding its biological significance in different organisms. Pin1
      was essential in HeLa cells, while Pin1-deficient mice showed no lethal
      phenotypes. We here identified a novel murine Pin1 isoform (mPin1L) consisting of
      the WW domain and the PPIase domain. Murine Pin1L shares 92% sequence identity
      with the wild-type Pin1 and shows wide tissue distribution with highest levels in
      mouse testis. The recombinant mPin1L is enzymatically active, but is
      approximately three times less efficient than Pin1 in catalyzing the cis/trans
      isomerization. These data suggest that mPin1L may serve as a surrogate for Pin1.
      The finding provides insights into phenotypic consequences for Pin1-null mice and
      may facilitate future biological study and pharmacological development in mice.

PMID- 17548054
TI  - Effects of Wnt-10b on hair shaft growth in hair follicle cultures.
AB  - Wnts are deeply involved in the proliferation and differentiation of skin
      epithelial cells. We previously reported the differentiation of cultured primary
      skin epithelial cells toward hair shaft and inner root sheath (IRS) of the hair
      follicle via beta-catenin stabilization caused by Wnt-10b, however, the effects
      of Wnt-10b on cultured hair follicles have not been reported. In the present
      study, we examined the effects of Wnt-10b on shaft growth using organ cultures of
      whisker hair follicles in serum-free conditions. No hair shaft growth was
      observed in the absence of Wnt-10b, whereas its addition to the culture promoted
      elongation of the hair shaft, intensive incorporation of BrdU in matrix cells
      flanking the dermal papilla (DP), and beta-catenin stabilization in DP and IRS
      cells. These results suggest a promoting effect of Wnt-10b on hair shaft growth
      that is involved with stimulation of the DP via Wnt-10b/beta-catenin signalling,
      proliferation of matrix cells next to the DP, and differentiation of IRS cells by
      Wnt-10b.

PMID- 17548055
TI  - TLR2 has a detrimental role in mouse transient focal cerebral ischemia.
AB  - A significant up-regulation of Toll-like-receptor (TLR) mRNAs between 3 and 48 h
      reperfusion time after induction of transient focal cerebral ischemia for 1h was
      revealed by applying global gene expression profiling in postischemic mouse
      brains. Compared to TLR4 and TLR9, TLR2 proved to be the most significantly up
      regulated TLR in the ipsilateral brain hemisphere. TLR2-protein was found to be
      expressed mainly in microglia in the postischemic brain tissue, but also in
      selected endothelial cells, neurons, and astrocytes. Additionally, TLR2-related
      genes with pro-inflammatory and pro-apoptotic capabilities were induced.
      Therefore we hypothesized that TLR2-signaling could exacerbate the primary brain
      damage after ischemia. Two days after induction of transient focal cerebral
      ischemia (1h), we found a significant decrease of the infarct volume in TLR2
      deficient mice compared to wild type mice (75+/-5 vs. 42+/-7 mm(3)). We conclude
      that TLR2 up-regulation and TLR2-signaling are important events in focal cerebral
      ischemia and contribute to the deterioration of ischemic damage.

PMID- 17548056
TI  - Treatment of keratin intermediate filaments with sulfur mustard analogs.
AB  - Sulfur mustard (SM) is an alkylating agent with a history of use as a chemical
      weapon. The chemical reactivity of sulfur mustard toward both proteins and
      nucleic acids coupled with the hours long delay between exposure and appearance
      of blisters has prevented the determination of the mechanism of blister
      formation. We have treated assembled keratin intermediate filaments with analogs
      of sulfur mustard to simulate exposure to SM. We find that treatment of intact
      filaments with chloroethyl ethyl sulfide (CEES) or mechlorethamine (MEC) produces
      aggregates of keratin filaments with little native appearing structure. Treatment
      of a mix of epidermal keratins 1/10 (keratin pair 1 and 10) and keratins 5/14
      with a sulfhydryl-specific modification reagent also results in filament
      abnormalities. Our results are consistent with the hypothesis that modification
      of keratins by SM would result in keratin filament destruction, leading to lysis
      of epidermal basal cells and skin blistering.

PMID- 17548057
TI  - Serotonin induces selective cleavage of the PKA RI subunit but not RII subunit in
      Aplysia neurons.
AB  - PKA type I and type II are activated in Aplysia neurons by stimulation with
      serotonin (5-HT), which causes long-term facilitation (LTF). The proteolysis of
      the regulatory subunit (R) is thought important for the persistent activation of
      PKA, which is necessary to produce LTF. In this study, we report that the type I
      regulatory subunit (RI) and type II regulatory subunit (RII) are differentially
      regulated by proteolytic cleavage. RI, but not RII, was selectively cleaved after
      5-HT treatment for 2h in Aplysia neurons. Interestingly, the proteasome inhibitor
      MG132 inhibited the cleavage of RI caused by 5-HT treatment in Aplysia neuron.
      Besides extracts from Aplysia ganglia treated with 5-HT cleaved (35)S-labeled RI
      synthesized in vitro, but not (35)S-labeled RII. This suggests that 5-HT induces
      the activation state of RI-specific proteolytic cleavage.

PMID- 17548058
TI  - A water-soluble extract from Cucurbita moschata shows anti-obesity effects by
      controlling lipid metabolism in a high fat diet-induced obesity mouse model.
AB  - During the screening of a variety of plant sources for their anti-obesity
      activity, it was found that a water-soluble extract, named PG105, prepared from
      stem parts of Cucurbita moschata, contains potent anti-obesity activities in a
      high fat diet-induced obesity mouse model. In this animal model, increases in
      body weight and fat storage were suppressed by 8-week oral administration of
      PG105 at 500 mg/kg, while the overall amount of food intake was not affected.
      Furthermore, PG105 protected the development of fatty liver and increased the
      hepatic beta-oxidation activity. Results from blood analysis showed that the
      levels of triglyceride and cholesterol were significantly lowered by PG105
      administration, and also that the level of leptin was reduced, while that of
      adiponectin was increased. To understand the underlying mechanism at the
      molecular level, the effects of PG105 were examined on the expression of the
      genes involved in lipid metabolism by Northern blot analysis. In the liver of
      PG105-treated mice, the mRNA level of lipogenic genes such as SREBP-1c and SCD-1
      was decreased, while that of lipolytic genes such as PPARalpha, ACO-1, CPT-1, and
      UCP-2 was modestly increased. Our data suggest that PG105 may have great
      potential as a novel anti-obesity agent in that both inhibition of lipid
      synthesis and acceleration of fatty acid breakdown are induced by this reagent.

PMID- 17548059
TI  - Peripheral N- and C-terminal domains determine deactivation kinetics of HCN
      channels.
AB  - Among four subtypes of mammalian HCN channels, HCN1 has the fastest activation
      and deactivation kinetics while HCN4 shows the slowest. We previously showed that
      the activation kinetics are determined mainly by S1, S1-S2, and the S6-cyclic
      nucleotide binding domain. However, the effects of those regions on the
      deactivation kinetics were relatively small. Therefore, we investigated the
      structural basis for deactivation kinetics. Substitution of the core region (from
      S3 to S6) between HCN1 and HCN4 did not affect deactivation kinetics. This
      suggests that the peripheral regions (outside of S3 to S6) determine subtype
      specific deactivation kinetics. Furthermore, we examined whether peripheral
      regions determined the deactivation kinetics across species by introducing the
      core region of DMIH (Drosophila homologue) into both HCN1 and HCN4. The DMIH core
      with HCN1 activated and deactivated more than threefold faster than that with
      HCN4. Taken together, the peripheral domains are diversified to create distinct
      kinetics.

PMID- 17548060
TI  - Characterization of DNA methylation change in stem cell marker genes during
      differentiation of human embryonic stem cells.
AB  - Pluripotent human embryonic stem cells (hESCs) have the distinguishing feature of
      innate capacity to allow indefinite self-renewal. This attribute continues until
      specific constraints or restrictions, such as DNA methylation, are imposed on the
      genome, usually accompanied by differentiation. With the aim of utilizing DNA
      methylation as a sign of early differentiation, we probed the genomic regions of
      hESCs, particularly focusing on stem cell marker (SCM) genes to identify
      regulatory sequences that display differentiation-sensitive alterations in DNA
      methylation. We show that the promoter regions of OCT4 and NANOG, but not SOX2,
      REX1 and FOXD3, undergo significant methylation during hESCs differentiation in
      which SCM genes are substantially repressed. Thus, following exposure to
      differentiation stimuli, OCT4 and NANOG gene loci are modified relatively rapidly
      by DNA methylation. Accordingly, we propose that the DNA methylation states of
      OCT4 and NANOG sequences may be utilized as barometers to determine the extent of
      hESC differentiation.

PMID- 17548061
TI  - Characterization of SynCAM surface trafficking using a SynCAM derived ligand with
      high homophilic binding affinity.
AB  - In order to better probe SynCAM function in neurons, we produced a fusion protein
      between the extracellular domain of SynCAM1 and the constant fragment of human
      IgG (SynCAM-Fc). Whether in soluble form or immobilized on latex microspheres,
      the chimera bound specifically to the surface of hippocampal neurons and
      recruited endogenous SynCAM molecules. SynCAM-Fc was also used in combination
      with Quantum Dots to follow the mobility of transfected SynCAM receptors at the
      neuronal surface. Both immobile and highly mobile SynCAM were found. Thus, SynCAM
      Fc behaves as a high affinity ligand that can be used to study the function of
      SynCAM at the neuronal membrane.

PMID- 17548062
TI  - Attenuation of reperfusion injury by renal ischemic postconditioning: the role of
      NO.
AB  - Ischemic postconditioning (Postcond) is defined as rapid intermittent
      interruptions of blood flow in the early phase of reperfusion and mechanically
      alters the hydrodynamics of reperfusion. Although Postcond has been demonstrated
      to attenuate ischemia/reperfusion (I/R) injury in the heart and brain, its roles
      to renal I/R injury remain to be defined. In the present study, we examined the
      role of Postcond in I/R injury in a right-nephrectomized rat model. Postcond
      prevents the renal dysfunction and cell apoptosis induced by I/R and increases
      nitric oxide (NO) release and renal NO synthase (endothelial, eNOS and inducible,
      iNOS) expression. In contrast, enhancement of endothelin-1 (ET-1) in the kidney
      after the reperfusion was markedly suppressed by Postcond. These findings
      indicate that Postcond can inhibit renal I/R injury. The protective effect of
      Postcond is closely related to the NO production following the increase in eNOS
      and iNOS expression and the suppressive effect of ET-1 overproduction.

PMID- 17548063
TI  - Regioselective sulfonation of dopamine by SULT1A3 in vitro provides a molecular
      explanation for the preponderance of dopamine-3-O-sulfate in human blood
      circulation.
AB  - SULT1A3 is an enzyme that catalyzes the sulfonation of many endogenous and
      exogenous phenols and catechols. The most important endogenous substrate is
      dopamine (DA), which is often used as a probe substrate for SULT1A3. We developed
      a new method for analyzing the SULT1A3 reaction products by high-performance
      liquid chromatography (HPLC) with electrochemical detection. The sulfonate donor
      3'-phosphoadenosine-5'-phosphosulfate (PAPS), DA and the two dopamine sulfates,
      DA-3-O-sulfate and DA-4-O-sulfate, can be separated within 3 min. This enables
      quantitation of the sulfates without radioactive PAPS or the precipitation of
      unreacted PAPS. Both sulfates were synthesized as reference substances and
      characterized by (1)H and (13)C nuclear magnetic resonance (NMR), mass
      spectrometry (MS) and tandem mass spectrometry (MS/MS). The purity of the
      dopamine sulfates was estimated by HPLC using a diode array detector. We
      determined the enzyme kinetic parameters for formation of DA-3-O-sulfate and DA-4
      O-sulfate using purified recombinant human SULT1A3. The reactions followed
      Michaelis-Menten kinetics up to 50 microM DA concentration, and strong substrate
      inhibition was observed at higher concentrations. The apparent K(m) values for
      sulfonation at both hydroxy groups were similar (2.21+/-0.764 and 2.59+/-1.06
      microM for DA-4-O-sulfate and DA-3-O-sulfate, respectively), but the V(max) was
      approximately six times higher for the formation of the 3-O-sulfate (344+/-139
      nmol/min/mg protein) than the 4-O-sulfate (45.4+/-16.5 nmol/min/mg protein).
      These results are in accordance with the observation that DA-3-O-sulfate is more
      abundant in human blood than DA-4-O-sulfate and that in the crystal structure of
      SULT1A3 with dopamine bound to the active site, the 3-hydroxy group is aligned to
      form hydrogen bonds with catalytic residues of the enzyme.

PMID- 17548064
TI  - The inhibitors of protein acylation, cerulenin and tunicamycin, increase voltage
      dependent Ca(2+) currents in the insulin-secreting INS 832/13 cell.
AB  - As it has been suggested that protein acylation plays a role in nutrient stimulus
      secretion coupling in the pancreatic beta-cell, we examined the insulin-secreting
      INS 832/13 beta-cell line for evidence that protein acylation was involved. The
      perforated whole-cell configuration was employed to voltage-clamp INS 832/13
      cells. Voltage pulses were applied and Ca(2+) currents measured in the presence
      and absence of the protein acylation inhibitors cerulenin and tunicamycin. Both
      inhibitors enhanced the peak amplitude of I(Ca,L). Both increased the peak inward
      current in the range between -40 and +30mV and shifted the apparent maximum
      current by 10mV in the hyperpolarizing direction without affecting the activation
      threshold of -40mV. The two drugs had qualitatively and quantitatively similar
      effects. Steady-state activation curves revealed that cerulenin and tunicamycin
      shifted the activation curves in the hyperpolarization direction. Activation time
      constants were significantly reduced in the presence of both drugs. The Ca(2+)
      charge influx was increased by the drugs at all potentials tested. In contrast to
      these effects on the L-type Ca(2+) channel, the two inhibitors of protein
      acylation had no effect on the ATP-sensitive K(+) channel. The results suggest
      that protein acylation exerts a tonic inhibitory effect on L-type Ca(2+) channel
      function in the insulin-secreting beta-cell.

PMID- 17548065
TI  - Dissecting the catalytic mechanism of a plant beta-D-glucan glucohydrolase
      through structural biology using inhibitors and substrate analogues.
AB  - Higher plant, family GH3 beta-D-glucan glucohydrolases exhibit exo-hydrolytic and
      retaining (e-->e) mechanisms of action and catalyze the removal of single
      glucosyl residues from the non-reducing termini of beta-D-linked glucosidic
      substrates, with retention of anomeric configuration. The broad specificity beta
      D-glucan glucohydrolases are likely to play roles in cell wall re-modelling, turn
      over of cell wall components and possibly in plant defence reactions against
      pathogens. Crystal structures of the barley beta-D-glucan glucohydrolase,
      obtained from both native enzyme and from the enzyme in complex with a substrate
      analogues and mechanism-based inhibitors, have enabled the basis of substrate
      specificity, the mechanism of catalysis, and the role of domain movements during
      the catalytic cycle to be defined in precise molecular terms. The active site of
      the enzyme forms a shallow 'pocket' that is located at the interface of two
      domains of the enzyme and accommodates two glucosyl residues. The propensity of
      the enzyme to hydrolyze a broad range of substrates with (1-->2)-, (1-->3)-, (1-
      >4)- and (1-->6)-beta-D-glucosidic linkages is explained from crystal structures
      of the enzyme in complex with non-hydrolysable S-glycoside substrate analogues,
      and from molecular modelling. During binding of gluco-oligosaccharides, the
      glucosyl residue at subsite -1 is locked in a highly constrained position, but
      the glucosyl residue at the +1 subsite is free to adjust its position between two
      tryptophan residues positioned at the entry of the active site pocket. The
      flexibility at subsite +1 and the projection of the remainder of the substrate
      away from the pocket provide a structural rationale for the capacity of the
      enzyme to accommodate and hydrolyze glucosides with different linkage positions
      and hence different overall conformations. While mechanism-based inhibitors with
      micromolar Ki constants bind in the active site of the enzyme and form esters
      with the catalytic nucleophile, transition-state mimics bind with their 'glucose'
      moieties distorted into the 4E conformation, which is critical for the nanomolar
      binding of these inhibitors to the enzyme. The glucose product of the reaction,
      which is released from the non-reducing termini of substrates, remains bound to
      the beta-D-glucan glucohydrolase in the -1 subsite of the active site, until a
      new substrate molecule approaches the enzyme. If dissociation of the glucose from
      the enzyme active site could be synchronized throughout the crystal, time
      resolved Laue X-ray crystallography could be used to follow the conformational
      changes that occur as the glucose product diffuses away and the incoming
      substrate is bound by the enzyme.

PMID- 17548066
TI  - In vitro gene delivery to HepG2 cells using galactosylated 6-amino-6
      deoxychitosan as a DNA carrier.
AB  - A chitosan derivative, 6-amino-6-deoxy chitosan (6ACT), was galactosylated and
      was investigated as a gene carrier. A series of galactose-modified 6ACT (Gal
      6ACT) with degrees of substitution (d.s.) ranging from 3% to 50% per pyranose
      were prepared by reductive alkylation with lactose. DNA retardation assays showed
      that the electrostatic interaction between Gal-6ACT and plasmid DNA was not
      changed by galactose modification up to 50% per pyranose of 6ACT. Gal-6ACT with a
      d.s. of 38% was bound to galactose-recognizing lectin, RCA120. A significant
      increase in transfection efficiency for HepG2 cells was observed at degree of
      substitutions ranging from 18% to 50% and at N/P values ranging from 1.5 to 2.5.
      Under optimum conditions, Gal-6ACT showed about 10 times higher efficiency than
      6ACT. However, a slight uptake by the galactose receptors on hepatocytes was
      observed by flow cytometric analysis. Moreover, Gal-6ACT with a d.s. of 38%
      mediated efficient gene transfer into both A549 and HeLa cells lacking the
      galactose receptor. These results suggest that the enhancement of transfection
      efficiency of Gal-6ACT was not due to the increase of receptor-mediated cellular
      uptake. In addition, the enhanced gene transfer efficiency was not specific to
      the galactose modification because the efficiency of glucose-modified 6ACT for
      HepG2 cells was similar as that of Gal-6ACT.

PMID- 17548067
TI  - Crystal structure and anticonvulsant activity of (+/-)-1,2:4,5-di-O
      isopropylidene-3,6-di-O-(2-propylpentanoyl)-myo-inositol.
AB  - The biological activity and crystal structure of (+/-)-1,2:4,5-di-O
      isopropylidene-3,6-di-O-(2-propylpentanoyl)-myo-inositol have been investigated.
      This compound shows better anticonvulsant activity than valproic acid (VPA) in
      the MES test as measured in mice. Its structure, determined from single-crystal X
      ray diffraction measurements, shows that the inositol ring deviates from the
      ideal chair conformation and that the two 2-propylpentanoyl groups are located on
      opposite ring positions. This molecular conformation lets carbonyl and hydroxyl
      oxygen atoms to be available for hydrogen-bonding interactions, hinders carbonyl
      carbon atoms, preventing metabolic enzymatic hydrolysis, and helps to rationalize
      the observed inactive profile in the PTZ test. The anticonvulsant activity
      profile suggests a mechanism different from that of VPA.

PMID- 17548068
TI  - Development of a computer-aided diagnosis system for continuous peritoneal
      dialysis: an availability of the simultaneous numerical optimization technique
      for kinetic parameters in the peritoneal dialysis model.
AB  - We developed a novel diagnostic system for continuous peritoneal dialysis, which
      evaluates the peritoneal permeability and hydraulic conductance (peritoneal
      function) by applying the kinetic model and a clinical test with minimum nursing
      time. Kinetic parameters for the peritoneal function were determined by the
      simultaneous numerical optimization techniques (SNOT). Furthermore dialysis
      outcome and ultrafiltration volume were estimated and predicted by using the
      kinetic model with a set of optimal kinetic parameters, which were in agreement
      with measured data (r(2)>0.82). The clinical implementation of the SNOT is very
      useful to explore the better prescriptions for each patient's clinical condition.

PMID- 17548069
TI  - Lupus anticoagulant and antibodies to beta 2-glycoprotein I, annexin V, and
      cardiolipin as a cause of recurrent spontaneous abortion.
AB  - The prevalence of lupus anticoagulant (LAC), anticardiolipin (ACA), anti-beta(2)
      glycoprotein I (beta(2)GPI), and antiannexin V antibodies were determined in 200
      recurrent spontaneous abortion (RSA) patients and 200 age-matched control women.
      ACA IgG was associated with early, while antiannexin V IgG and LAC were
      associated with late, and ACA IgG, antiannexin V IgG, and LAC were associated
      with combined early + late RSA, thereby recommending inclusion of their screening
      in RSA workout.

PMID- 17548070
TI  - Mycoplasma genitalium, Chlamydia trachomatis, and tubal factor infertility--a
      prospective study.
AB  - OBJECTIVE: To determine the presence of M. genitalium and C. trachomatis in women
      attending fertility clinics and to follow these women for the effects of previous
      infections or tubal damage on pregnancy rate and outcome. DESIGN: Prospective
      study. SETTING: Fertility clinics and university. PATIENT(S): Two hundred twelve
      couples attending fertility clinics. INTERVENTION(S): Blood and cervical swab
      samples from the women. Tubal status was assessed by culdoscopy and/or
      laparoscopy. MAIN OUTCOME MEASURE(S): Presence of M. genitalium and C.
      trachomatis was determined by polymerase chain reaction. Serum samples were
      tested for antibodies against M. genitalium and C. trachomatis. RESULT(S): One
      swap sample was positive to C. trachomatis and none positive to M. genitalium.
      Thirty of the 194 women had tubal factor infertility (TFI); 23% and 17% of women
      with TFI had antibodies to C. trachomatis and M. genitalium, respectively,
      compared with 15% and 4%, respectively, of women with normal tubes; 36% and 14%
      of women with a self-reported history of pelvic inflammatory disease (PID) were
      seropositive to C. trachomatis and M. genitalium, respectively, compared with 10%
      and 6%, respectively, of women without past PID. CONCLUSION(S): A strong antibody
      response against M. genitalium or C. trachomatis but no sign of current or
      chronic infection was found in women with TFI, indicating that previous
      infections caused by these microorganisms may have resulted in permanent damage
      and occlusion of the fallopian tubes.

PMID- 17548071
TI  - Peritoneal fluid macrophages in endometriosis: correlation between the expression
      of estrogen receptors and inflammation.
AB  - OBJECTIVE: To investigate the expression of estrogen receptors (ERs) and
      inflammatory cytokines in macrophages obtained from peritoneal fluid (PF) of
      women with endometriosis. DESIGN: Comparative immunocytochemical study. SETTING:
      University hospital. PATIENT(S): Thirty women with endometriosis and 22 controls.
      INTERVENTION(S): The PF samples were collected at laparoscopy. MAIN OUTCOME
      MEASURE(S): The expression of ERalpha, ERbeta, differentiation markers (CD68, NCL
      MACRO, HAM56), and inflammatory cytokines (interleukin [IL]-1beta, tumor necrosis
      factor-alpha [TNF-alpha], IL-6) in PF macrophages was determined. RESULT(S): The
      expression of CD68, NCL-MACRO, HAM56, TNFalpha, IL-6, and IL-1beta was
      significantly higher in PF macrophages obtained from women with endometriosis
      than in controls. The ERalpha and ERbeta had significantly higher expression in
      macrophages of women with endometriosis than in controls. A positive correlation
      was observed between the expression of ERalpha and ERbeta both in women with and
      without endometriosis. The ERalpha expression was positively correlated with the
      expression of inflammatory cytokines in women with endometriosis but not in
      controls; ERbeta expression was correlated to the expression of inflammatory
      cytokines in the both groups. CONCLUSION(S): There is a correlation between the
      expression of ERbeta and proinflammatory cytokines both in women with and without
      endometriosis. The expression of ERalpha correlates with cytokine production
      selectively in women with endometriosis but not in controls.

PMID- 17548073
TI  - Effects of obesity on assisted reproductive technology outcomes.
AB  - Mounting evidence has shown that increased body mass index has a significant
      adverse effect on pregnancy and miscarriage rates in women seeking to conceive
      naturally. Several studies have sought to determine the effects of obesity on the
      endometrium by analyzing outcomes in patients receiving ovum donation.

PMID- 17548075
TI  - A suprapubic dermoid cyst confused with cutaneous endometriosis: a case report.
AB  - OBJECTIVE: To describe a case of suprapubic dermoid cyst that had been mistaken
      for cutaneous endometriosis. DESIGN: Case report. SETTING: Department of
      Obstetrics and Gynecology, Seoul National University Hospital, Korea. PATIENT(S):
      A 22-year-old woman with a 5-year history of a slowly growing suprapubic mass,
      which had begun to bleed intermittently 6 months before presentation.
      INTERVENTION(S): Complete excision of the suprapubic mass and primary closure of
      the wound. MAIN OUTCOME MEASURE(S): The natural course of the suprapubic dermoid
      cyst and histologic findings. RESULT(S): The excised suprapubic mass was
      histologically diagnosed as a dermoid cyst. CONCLUSION(S): Subcutaneous dermoid
      cysts should be part of the differential diagnosis of suprapubic wall masses.

PMID- 17548076
TI  - C-reactive protein levels are unaffected by metformin during pretreatment and an
      IVF cycle in women with polycystic ovary syndrome.
AB  - OBJECTIVE: Low-grade chronic inflammation, evaluated by serum C-reactive protein
      (CRP) levels, has been connected with the polycystic ovary syndrome (PCOS).
      Effects of metformin on CRP before and during IVF treatment in women with PCOS
      are unknown. DESIGN: A prospective double-blind placebo-controlled study.
      SETTING: Single-center IVF clinic. PATIENT(S): Sixty-three PCOS women.
      INTERVENTION(S): Treatment with 2000 mg/day metformin or identical placebo
      tablets for at least 14 weeks before and then during IVF treatment, ending on the
      day of hCG injection. MAIN OUTCOME MEASURE(S): The CRP levels at five time points
      ending on the day of ovum collection. RESULT(S): At inclusion of infertile
      untreated PCOS women, body mass index associated with CRP in multivariable
      regression analysis (r = 0.18). Androgen levels did not associate with CRP
      levels. Metformin did not influence CRP levels during pretreatment or IVF cycle.
      After hCG injection, CRP increased in both the metformin and the placebo groups
      with no significant difference between the groups. CONCLUSION(S): In infertile
      PCOS women, CRP levels are unaffected by metformin treatment. The CRP level
      increases during IVF treatment, and this increase is unaffected by concomitant
      metformin. We observed an association between CRP levels and body mass index.

PMID- 17548077
TI  - Gender-related differences in oxidative stress levels among elderly patients with
      coronary artery disease.
AB  - OBJECTIVE: To evaluate whether gender-related differences exist concerning
      oxidative stress levels in aged patients with coronary artery disease (CAD).
      DESIGN: Case-control. SETTING: Clinical and research center. PATIENT(S): Elderly
      subjects of both genders with or without CAD. INTERVENTION(S): None. MAIN OUTCOME
      MEASURE(S): Serum hydroperoxides (HP) as index of oxidative stress levels.
      RESULT(S): The HP levels were comparable in aged control subjects of both genders
      (376 +/- 20 arbitrary units [AU] in women, 333 +/- 19 AU in men) but
      significantly increased in CAD (456 +/- 15 AU) compared with all control subjects
      (357 +/- 14 AU). Moreover, among CAD patients, the HP levels were higher in women
      than in men (536 +/- 33 AU and 428 +/- 15 AU, respectively). Multivariate
      analysis, in which CAD represented the dependent variable, indicated that
      dyslipidemia was independently associated with CAD in men (odds ratio [OR] 5.8),
      whereas HP >50th percentile represented the only strong independent risk factor
      for CAD in elderly women (OR 8.4). CONCLUSION(S): Differences in oxidative stress
      levels between elderly males and females might provide a biochemical basis for
      the epidemiologic differences in CAD, which might help to open new opportunities
      in the management of patients with cardiovascular disease from a gender point of
      view.

PMID- 17548078
TI  - Roles of leptin and ghrelin in eating disorders?

PMID- 17548080
TI  - Tubal transport of spermatozoa does not appear to be dependent on normal cilia
      function.
AB  - OBJECTIVE: To report the case of a woman with Kartagener's syndrome with complete
      immotility of ciliae and normal transport of spermatozoa. DESIGN: Case report.
      PATIENTS: A 31-year-old woman with Kartagener's syndrome. SETTING: Medical
      university-affiliated teaching hospital. INTERVENTION(S): Ultrasonography,
      hysterosalpingoscintigraphy using technetium-99m-labeled macroaggregates of human
      serum albumin, application of oxytocin. MAIN OUTCOME MEASURE(S): Dynamic
      anteroposterior scintigraphy using a gamma camera. RESULT(S): The transport of
      labeled macrospheres through the fallopian tube into the peritoneal cavity on the
      side of the leading follicle, compared to the contralateral oviduct where the
      labeled material may have accumulated within the fallopian tube, is similar to
      those reported in normal fertile women. CONCLUSION(S): Transport of spermatozoa
      is not dependent on normal ciliary function.

PMID- 17548081
TI  - Single cell diagnosis using comparative genomic hybridization after preliminary
      DNA amplification still needs more tweaking: too many miscalls.

PMID- 17548082
TI  - Sperm immobilized before intracytoplasmic sperm injection undergo ultrastructural
      damage and acrosomal disruption.
AB  - The aim of this study was to describe morphologic sperm changes observed via
      scanning electron microscopy and the acrosomal status resulting from
      immobilization and micromanipulation. The manipulations made on sperm before
      intracytoplasmic sperm injection were the possible cause of sperm ultrastructural
      damages and could trigger an acrosome reaction.

PMID- 17548083
TI  - Cryopreserved blastocyst transfer: impact of gonadotropin-releasing hormone
      agonist versus antagonist in the previous oocyte retrieval cycles.
AB  - OBJECTIVE: To assess any detrimental effect of gonadotropin-releasing hormone
      (GnRH) antagonists on oocyte quality and embryo development by comparing the
      outcome of cryopreserved-thawed blastocyst transfers for cycles using a GnRH
      agonist or GnRH antagonist protocol for the controlled ovarian stimulation in the
      oocyte retrieval cycle. DESIGN: Retrospective comparative study. SETTING: Private
      IVF center. PATIENT(S): Seventy-seven women who underwent cryopreserved-thawed
      blastocyst transfer. INTERVENTION(S): The patients were divided into two groups
      based on whether they had been treated using a GnRH agonist long protocol (n =
      44) or a GnRH antagonist multiple-dose protocol (n = 33) during the previous
      oocyte retrieval cycle. Cryopreserved-thawed blastocysts were transferred after
      endometrial preparation without pituitary suppression using a GnRH agonist. MAIN
      OUTCOME MEASURE(S): Implantation and clinical pregnancy rates. RESULT(S): The
      postthaw survival rate and numbers of good quality blastocysts transferred were
      similar for the GnRH agonist and GnRH antagonist groups. Implantation and
      pregnancy rates for cryopreserved-thawed blastocyst transfer for the GnRH agonist
      group versus the GnRH antagonist group were 21.0% (25 of 119) versus 29.0% (27 of
      93) and 38.6% (17 of 44) versus 51.5% (17 of 33), respectively, which was not
      statistically significantly different. CONCLUSION(S): No difference was found in
      terms of implantation and pregnancy rates when a GnRH agonist or GnRH antagonist
      was used in the previous oocyte retrieval cycle. Our results suggest that GnRH
      antagonists do not have a detrimental effect on oocyte quality or embryo
      development.

PMID- 17548084
TI  - "Tenderness-guided" transvaginal ultrasonography: a new method for the detection
      of deep endometriosis in patients with chronic pelvic pain.
AB  - OBJECTIVE: To determine the accuracy of transvaginal ultrasonography (TVUS) using
      a modified "tenderness-guided" approach in the diagnosis of deep endometriosis of
      the cul-de-sac, retrocervical region, and rectovaginal septum. DESIGN:
      Prospective study. SETTING: Academic department of obstetrics and gynecology.
      PATIENT(S): Fifty women scheduled for laparoscopy for chronic pelvic pain.
      INTERVENTION(S): All patients underwent TVUS. The modified tenderness-guided
      approach consisted of TVUS combined with the introduction of 12 mL of ultrasound
      transmission gel (instead of the usual 4 mL) in the probe cover to create a stand
      off to visualize the near-field area. The posterior fornix was evaluated
      accurately with an up-and-down sliding movement of the probe. In addition, when
      the patient indicated that tenderness was evoked by the probe's pressure, the
      sliding movement was stopped, and particular attention was paid to the painful
      site for detection of endometriosis lesions. MAIN OUTCOME MEASURE(S):
      Sensitivity, specificity, and kappa values. RESULT(S): Using this approach, we
      obtained a specificity of 95% with a sensitivity of 90%, associated with a very
      high kappa value of 0.86 (95% CI, 0.56-0.91). CONCLUSION(S): Our new TVUS
      approach appears to be an accurate, inexpensive, and less invasive method for the
      diagnosis of deep endometriosis.

PMID- 17548085
TI  - Is there a special subgroup of males with adult-onset idiopathic
      hypogonadotrophic hypogonadism who may respond with increases in sperm
      concentration after clomiphene citrate?

PMID- 17548087
TI  - Finding the right stuff--search strategies can and do make a difference!

PMID- 17548088
TI  - In vitro effect of dehydroepiandrosterone sulfate on steroid receptors,
      aromatase, cyclooxygenase-2 expression, and steroid hormone production in
      preovulatory human granulosa cells.
AB  - OBJECTIVE: To examine the effect of a low concentration of DHEAS on the
      expression of the androgen receptor, estrogen receptor alpha and beta,
      progesterone receptor, aromatase, 3-beta-hydroxysteroid dehydrogenase, and
      cyclooxygenase-2 in human preovulatory granulosa cells, and to measure their
      production of steroid hormones (estrone, estradiol, progesterone,
      androstenedione, and testosterone). DESIGN: Analysis of cultured primary human
      preovulatory granulosa cells by real-time reverse-transcriptase polymerase chain
      reaction and assays of hormone production. SETTING: Osaka City University
      Postgraduate School of Medicine. INTERVENTION(S): Preovulatory granulosa cells
      were collected from follicular fluid obtained from patients undergoing
      transvaginal oocyte retrieval with ultrasound guidance. The cells were cultured
      in the absence or presence of a low concentration of DHEAS. Real-time reverse
      transcriptase polymerase chain reaction was performed to quantify the RNA
      expression of the investigated genes, and steroid hormone (estrone, estradiol,
      progesterone, androstenedione, and testosterone) levels were measured in the
      culture medium. MAIN OUTCOME MEASURE(S): Changes in [1] the levels of mRNAs
      encoding androgen receptor, estrogen receptor alpha, estrogen receptor beta,
      progesterone receptor, aromatase, 3-beta-hydroxysteroid dehydrogenase, and
      cyclooxygenase-2; and [2] the levels of steroid hormones (estrone, estradiol,
      progesterone, androstenedione, and testosterone) in the culture medium.
      RESULT(S): Treatment of granulosa cells with 20 ng/mL DHEAS increased the
      expression of androgen receptor, aromatase, 3-beta-hydroxysteroid dehydrogenase,
      and cyclooxygenase-2, reduced the expression of estrogen receptor beta, and
      increased estrone and estradiol levels, but had no effect on progesterone,
      androstenedione, or testosterone levels. CONCLUSION(S): DHEAS may be an essential
      trigger of ovulation.

PMID- 17548089
TI  - Tibolone histology of the endometrium and breast endpoints study: design of the
      trial and endometrial histology at baseline in postmenopausal women.
AB  - OBJECTIVE: To address the endometrial safety of tibolone. DESIGN: The Tibolone
      Histology of the Endometrium and Breast Endpoints Study (THEBES) is a randomized,
      double-blind, parallel-group trial of tibolone compared with continuous combined
      conjugated equine estrogen (CEE) and medroxyprogesterone acetate (MPA). SETTING:
      Multi-country, multi-center ambulatory care setting. PATIENT(S): A total of 5,185
      subjects were screened, and biopsies were obtained from 4,446 women.
      INTERVENTION(S): Participants were randomized in a 1:1:2 ratio, to tibolone (1.25
      or 2.5 mg/d) or CEE-MPA. MAIN OUTCOME MEASURE(S): The one-sided 95% confidence
      intervals for the incidence of hyperplasia or cancer were evaluated for tibolone
      compared with CEE-MPA. RESULT(S): Endometrial biopsy results at baseline:
      atrophic (87.29%), inactive (0.25%), proliferative (6.12%), secretory (2.86%),
      menstrual type (0.40%), and hyperplasia (0.18%). Only subjects with atrophic or
      inactive endometrium were eligible for this study, and 3% of the women at
      screening either had no tissue (0.18%) or had an amount of tissue that was
      insufficient for diagnosis (2.72%). Three thousand two hundred forty
      postmenopausal women with a mean (+/-SD) age of 54.4 +/- 4.4 years and a mean
      time since menopause of 4.5 +/- 3.6 years were randomized. CONCLUSION(S): The
      Tibolone Histology of the Endometrium and Breast Endpoints Study is a
      prospective, randomized clinical trial, designed to provide evidence of the
      endometrial safety of tibolone compared with estrogen and progestogen. Screening
      endometrial histology shows a low prevalence of endometrial hyperplasia (0.18%)
      and no carcinoma.

PMID- 17548090
TI  - Leishmania MAP kinases--familiar proteins in an unusual context.
AB  - Mitogen-activated protein kinases are well-known mediators of signal transduction
      of higher eukaryotes regulating important processes like proliferation,
      differentiation, stress response and apoptosis. In Leishmania, the typical three
      tiered module of MAP kinase signal transduction pathways is present. However,
      typical activators like cell surface receptors and substrates such as RNA
      polymerase II transcription factors are missing. Here, I describe the set of 15
      putative mitogen-activated protein kinases encoded in the Leishmania genome and
      discuss their potential function.

PMID- 17548091
TI  - Chromatographic selectivity study of 4-fluorophenylacetic acid positional isomers
      separation.
AB  - Unique properties of the fluorine atom stimulate widespread use and development
      of new organofluorine compounds in agrochemistry, biotechnology and pharmacology
      applications. However, relatively few synthetic methods exhibit a high degree of
      fluorination selectivity, which ultimately results in the presence of
      structurally related fluorinated isomers in the synthetic product. This outcome
      is undesirable from a pharmaceutical perspective as positional isomers possess
      different reactivity, biological activity and toxicity as compared to the desired
      product. It is advantageous to control positional isomers in the early stages of
      the synthetic process, as rejection and analysis of these isomers will likely
      become more difficult in later stages. The current work reports the development
      of a chromatographic analysis of 2- and 3-fluorophenylacetic acid positional
      isomer impurities in 4-fluorophenylacetic acid (4-FPAA), a building block in the
      synthesis of an active pharmaceutical ingredient. The method is employed as a
      part of a Quality by Design Approach to control purity of the starting material
      in order to eliminate the presence of undesirable positional isomers in the final
      drug substance. During method development, a wide range of chromatographic
      conditions and structurally related positional isomer probe molecules were
      exploited in an effort to gain insight into the specifics of the separation
      mechanism. For the systems studied it was shown that the choice of organic
      modifier played a key role in achieving acceptable separation. Further studies
      encompassed investigation of temperature influence on retention and selectivity
      of the FPAA isomers separation. Thermodynamic analysis of these data showed that
      the selectivity of the 2- and 4- fluorophenylacetic acids separation was
      dominated by an enthalpic process, while the selectivity of the 4- and 3
      fluorophenylacetic acids separation was exclusively entropy driven (Delta(DeltaH
      degrees approximately 0). Studies of chromatographic behavior were complemented
      by solid state NMR experiments which provided valuable information regarding the
      relationship between stationary phase solvation and selectivity.

PMID- 17548092
TI  - From tolerance to autoimmunity: is there a risk in early life vaccination?
AB  - The potential for vaccines to act as triggers of autoimmune reactions has
      received much recent attention. Such an association is very poorly defined
      mechanistically, but may potentially involve epitope mimicry between vaccinal and
      self antigen, or the immuno-stimulatory effects of vaccine adjuvant. If such
      reactions occur, they are more likely to involve adults than infants in early
      life, as a reflection of the immunological immaturity of the newborn. There has
      been a recent focus in immunology on the link between innate and adaptive
      immunity provided by dendritic cells and the range of Toll-like receptors (TLRs)
      that are the point of first contact of these cells with microbial antigen. These
      interactions appear to determine the nature of the subsequent adaptive immune
      response and whether it may be mediated by Th1, Th2, Th17 or T regulatory
      populations. TLR interactions may also be significant in the induction of
      vaccinal immunity and agonists of these receptors are being developed as
      potential vaccine adjuvants. There are differences in cytokine production of
      adult and newborn dendritic cells, and these differences must be considered in
      the application of such novel adjuvants to products intended for either age
      group.

PMID- 17548093
TI  - Immune responsiveness in the neonatal period.
AB  - The maintenance of pregnancy requires suppression of the maternal immune system
      which would naturally recognize the developing fetus as an allograft and seek to
      destroy it by mounting a Th1 regulated cytotoxic immune response. During
      pregnancy a range of soluble factors are produced by the placenta which switch
      maternal immune regulation towards a protective Th2 phenotype. These factors also
      influence the developing fetal immune system and all newborns initially have an
      immunological milieu skewed towards Th2 immunity. Vaccination during the neonatal
      period must therefore overcome the dual challenge of the inhibitory effect of
      maternally derived antibody and this natural Th2 regulatory environment. One
      means of overcoming these obstacles is by the use of adjuvant systems that can
      redirect the neonatal immune response towards an appropriate Th1 regulated
      reaction that affords protection from infectious disease. In this overview,
      experiments are described in which viral antigens incorporated into immune
      stimulatory complexes (ISCOMs) are able to induce immune responses with balanced
      Th1 and Th2 regulation in neonatal mice, as evidenced by the nature of the IgG
      subclass response and cytokine profile, and the induction of cytotoxic
      lymphocytes. ISCOM adjuvanted vaccines are able to induce similar protective
      immunity in the newborn of larger animal species including cattle, horses and
      dogs.

PMID- 17548094
TI  - Toxicogenomics: overview and potential applications for the study of non-covalent
      DNA interacting chemicals.
AB  - Non-covalent DNA interacting agents, DNA-groove binding chemicals and DNA
      intercalators, are generally considered less cytotoxic than agents producing
      covalent DNA adducts and other DNA damage. Although the impact of non-covalent
      compound-DNA interactions on convoluted molecular and biochemical pathways is not
      well characterized, the most prominent effects include DNA conformational and
      related structural perturbations, interference with normal DNA protein
      interactions, such as topoisomerases, as well as effects on mitochondrial DNA and
      function. The cellular responses to such perturbations would be expected to
      include changes in transcription of a variety of genes. The emerging field of
      toxicogenomics seeks to exploit gene responses to define expression profiling
      signatures for various types of drugs and toxicants, and to provide mechanistic
      insight into their cellular effects. There are a variety of examples whereby
      different classes of genotoxicants and non-genotoxic agents can be distinguished
      by gene expression profiling using functional genomics approaches, which survey
      global transcriptional responses. In this review, we will discuss the promises
      and precautions in the use of functional genomics approaches to characterize
      stress agents including non-covalent DNA interacting agents.

PMID- 17548095
TI  - Are we sensitive to valence differences in emotionally negative stimuli?
      Electrophysiological evidence from an ERP study.
AB  - The present study investigated whether the human brain is sensitive to valence
      differences in emotionally negative stimuli by recording event-related potentials
      (ERPs) for extremely negative (EN), moderately negative (MN), and neutral
      pictures while subjects perform a standard/deviant categorization task,
      irrespective of the emotional valence of the deviants. Using the same design, we
      also investigated the sensitivity of the human brain to valence differences in
      emotionally positive stimuli. Experiment 1 showed that EN stimuli elicited more
      negative deflections than MN stimuli in the early P2 and N2, later P3, and slow
      negative wave (SNW) components. In contrast, there were no differences in
      amplitude or latency in these components during the extremely positive (EP) and
      moderately positive (MP) conditions of Experiment 2. This suggests that humans
      are only sensitive to valence differences in negative stimuli, and that these
      negative valences could be processed differentially throughout the information
      processing stream even when individuals are highly engaged in a non-emotional
      task.

PMID- 17548096
TI  - Three oxidative metabolites of indole-3-acetic acid from Arabidopsis thaliana.
AB  - Three metabolites of indole-3-acetic acid (IAA), N-(6-hydroxyindol-3-ylacetyl)
      phenylalanine (6-OH-IAA-Phe), N-(6-hydroxyindol-3-ylacetyl)-valine (6-OH-IAA
      Val), and 1-O-(2-oxoindol-3-ylacetyl)-beta-d-glucopyranose (OxIAA-Glc), were
      found by a liquid chromatography-electrospray ionization-tandem mass spectrometry
      (LC-ESI-MS/MS)-based search for oxidative IAA metabolites during the vegetative
      growth of Arabidopsis. Their structures were confirmed by making a comparison of
      chromatographic characteristics and mass spectra between naturally occurring
      compounds and synthetic standards. An incorporation study using deuterium-labeled
      compounds showed that 6-OH-IAA-Phe and 6-OH-IAA-Val were biosynthesized from IAA
      Phe and IAA-Val, respectively, which strongly suggested the formation of these
      amino acid conjugates of IAA in plants. Both 6-OH-IAA-Phe and 6-OH-IAA-Val were
      inactive as auxins, as indicated by no significant root growth inhibition in
      Arabidopsis. Quantitative analysis demonstrated that OxIAA-Glc was present in the
      largest amount among the metabolites of IAA in Arabidopsis, suggesting that the
      conversion into OxIAA-Glc represents the main metabolic process regarding IAA in
      Arabidopsis.

PMID- 17548097
TI  - Achieving good standards in health promoting schools: preliminary analysis one
      year after the implementation of the Hong Kong Healthy Schools Award scheme.
AB  - BACKGROUND: Improving health literacy can be a strategy for the achievement of
      public health goals, and the concept of the Health Promoting School can help to
      build on the health literacy of students. The Centre for Health Education and
      Health Promotion of The Chinese University of Hong Kong launched the Hong Kong
      Healthy Schools Award (HKHSA) in 2001. This paper reports the results for the ten
      secondary schools that underwent assessment in 2002. METHODS: Based on the
      overall score for each school, cluster analysis was performed. Each cluster of
      schools reflected different levels of HKHSA achievement. RESULTS: This study has
      shown that those schools reaching high Health Promoting School standards have
      adopted the concept of a whole school approach in addressing health and social
      issues, rather than topic-based and school-located health promotion. The schools
      performing less satisfactorily mainly follow a prescriptive approach.
      CONCLUSIONS: These results are a good source of reference for other schools in
      their Health Promoting Schools programmes.

PMID- 17548098
TI  - Animal models of human African trypanosomiasis--very useful or too far removed?
AB  - Animal models of human African trypanosomiasis, also known as sleeping sickness,
      have been used for many years both to investigate disease pathogenesis and to
      test novel drug therapies. Model systems used have included mice, rats and non
      human primates such as monkeys. Whilst such animal models have some definite but
      unavoidable limitations, it is argued that these are outweighed by their
      advantages. The latter include the ability to investigate disease pathogenesis
      mechanistically and the mechanisms of trypanosome traversal of the blood-brain
      barrier, as well as the identification of new potential drug targets and staging
      biomarkers, new drug therapies and combinations, and potential drug toxicity.

PMID- 17548099
TI  - Study of the neuronal effects of ouabain and palytoxin and their binding to Na,K
      ATPases using an optical biosensor.
AB  - The phycotoxin palytoxin (PTX) binds to Na,K-ATPase, inhibiting its activity and
      converting the pump into a channel. These mechanisms are poorly understood. We
      examined the effect of PTX on membrane potential (E(m)), intracellular calcium
      concentration ([Ca2+]i) and intracellular pH (pH(i)) in primary cultures of
      cerebellar granule cells (CGC) and compared PTX and ouabain actions in the same
      cellular parameters. In this system, PTX caused depolarization, intracellular
      calcium increase and acidification. This is similar to the effect of ouabain.
      Preincubation of the cells with ouabain, before addition of PTX, altered E(m),
      [Ca2+]i, and pH(i) in a fashion similar to that of ouabain alone. This suggest a
      direct interaction of PTX with the Na,K-ATPase. Therefore, we used a resonant
      mirror biosensor to evaluate the binding of PTX and ouabain to immobilized Na,K
      ATPase. Ouabain binding to immobilized Na,K-ATPase was concentration-dependent.
      No binding of PTX to Na,K-ATPase was observed with up to 10 microM, or with PTX
      addition in the presence of ATP. The fact that ouabain binds to the pump in an
      immobilized conformation whereas not binding of PTX was observed indicates that
      PTX and ouabain do not share the same binding site, and PTX binding may require
      the tridimensional pump structure.

PMID- 17548100
TI  - Spermine isolated and identified as the major trypanocidal compound from the
      snake venom of Eristocophis macmahoni causes autophagy in Trypanosoma brucei.
AB  - The snake venom from the leaf-nosed viper Eristocophis macmahoni was analyzed
      regarding its toxic effects on the bloodstream form of Trypanosoma brucei. A
      considerable trypanocidal effect was measured with an IC5 value of 186 ng/ml in
      bloodstream form parasites. Following several high performance liquid
      chromatography (HPLC) separation steps, the major trypanocidal activity was
      assigned to a single fraction by in vitro toxicity assays. Analysis by off-line
      ESI-MS(n) revealed an m/z value of 202.2 for the precursor ion and fragment ions
      of m/z=129.1 (MS2) and 112.1 (MS3), respectively, clearly corresponding to the
      molecular mass and the fragmentation pattern of the polyamine spermine.
      Quantification of spermine within the viper venom using an on-line hydrophilic
      interaction chromatography (HILIC) ESI-MS method revealed that this compound
      constituted approximately 1% of the dry venom mass. The polyamine oxidase
      activity in the fetal calf serum used for cultivation was responsible for a
      trypanocidal effect of pure spermine in the low micromolar range, whereas the
      antitrypanosomal activity of crude snake venom was virtually independent from
      serum, suggesting the oxidation of spermine by intrinsic venom components. Using
      fetal calf serum, spermine was shown to induce autophagy in the parasites using
      transmission electron microscopy (TEM).

PMID- 17548101
TI  - Purification and properties of hyaluronidase from Hippasa partita (funnel web
      spider) venom gland extract.
AB  - Spider venom is a complex mixture of protein and peptide toxins. Hyaluronidase a
      'spreading factor' has not been studied extensively in spider venom. In this
      paper, we describe the purification and characterization of a hyaluronidase from
      Hippasa partita venom gland extract. Hyaluronidase (HPHyal) has been purified by
      the successive chromatography on a Sephadex G-100 and on CM-Sephadex C-25
      columns. HPHyal has been purified to an extent of about approximately 20-folds.
      The molecular mass was found to be 42.26 kDa by matrix-assisted laser desorption
      ionization time of flight (MALDI-TOF) mass spectrometry. HPHyal was optimally
      active at pH 5.8 at 37 degrees C and in the presence of 300 mM NaCl in the
      reaction mixture. HPHyal showed absolute specificity for hyaluronan and belongs
      to neutral active group of enzymes. HPHyal revealed single-precipitin line, while
      venom gland extract revealed multiple bands in Western blotting with the
      antiserum prepared against venom gland extract. HPHyal indirectly potentiates the
      myotoxicity of VRV-PL-VIII myotoxin and also the hemorrhagic potency of
      hemorrhagic complex-I. Cations, Na(+) and K(+) enhanced the activity and chloride
      ions do not have any effect while, divalent cations, inhibited the enzyme
      activity.

PMID- 17548102
TI  - Rotating dotted ellipses: motion perception driven by grouped figural rather than
      local dot motion signals.
AB  - Unlike the motion of a continuous contour, the motion of a single dot is
      unambiguous and immune to the aperture problem. Here we exploit this fact to
      explore the conditions under which unambiguous local motion signals are used to
      drive global percepts of an ellipse undergoing rotation. In previous work, we
      have shown that a thin, high aspect ratio ellipse will appear to rotate faster
      than a lower aspect ratio ellipse even when the two in fact rotate at the same
      angular velocity [Caplovitz, G. P., Hsieh, P. -J., & Tse, P. U. (2006) Mechanisms
      underlying the perceived angular velocity of a rigidly rotating object. Vision
      Research, 46(18), 2877-2893]. In this study we examined the perceived speed of
      rotation of ellipses defined by a virtual contour made up of evenly spaced dots.
      RESULTS: Ellipses defined by closely spaced dots exhibit the speed illusion
      observed with continuous contours. That is, thin dotted ellipses appear to rotate
      faster than fat dotted ellipses when both rotate at the same angular velocity.
      This illusion is not observed if the dots defining the ellipse are spaced too
      widely apart. A control experiment ruled out low spatial frequency "blurring" as
      the source of the illusory percept. CONCLUSION: Even in the presence of local
      motion signals that are immune to the aperture problem, the global percept of an
      ellipse undergoing rotation can be driven by potentially ambiguous motion signals
      arising from the non-local form of the grouped ellipse itself. Here motion
      perception is driven by emergent motion signals such as those of virtual contours
      constructed by grouping procedures. Neither these contours nor their emergent
      motion signals are present in the image.

PMID- 17548103
TI  - Influence of dissolved organic matter on estrone removal by NF membranes and the
      role of their structures.
AB  - The influence of different dissolved organic matter (DOM) on the removal of
      steroid hormone estrone during nanofiltration (NF) processes was investigated.
      Commercial dextran and humic acid (HA) as well as hydrophobic acid fraction
      (HpoA) derived from treated effluent were selected as DOM. To better understand
      the mechanism by which they affect estrone transport across NF membrane, the
      structural characteristics of DOM were also examined. The experimental results
      showed that DOM studied displayed obviously diverse impacts on estrone removal by
      NF membranes. These impacts were found to correlate with the structural
      characteristics of DOM. The presence of dextran without aromatic ring had little
      effects on the fate and transport of estrone during NF processes. The addition of
      HA without phenolic groups but great aromaticity improved estrone adsorption on
      membrane significantly while the "enhancement effect" on estrone rejection was
      limited. Moreover, estrone rejection by NF membranes was obviously increased by
      the presence of HpoA which possesses both phenolic groups and aromaticity. Some
      of the findings reported may be critically important for understanding the
      removal mechanism of estrone by NF membrane in real water matrix where various
      DOM co-present.

PMID- 17548104
TI  - Effects of low or medium-pressure UV irradiation on the release of intracellular
      microcystin.
AB  - UV irradiation could be an alternative growth inhibition treatment against toxic
      Microcystis blooms in lakes. This study examined the effect of UV irradiation on
      the release of toxic intracellular microcystin. Conventional algicidal treatment
      (e.g. copper sulfate) was known to cause rapid release of intracellular
      microcystin and additional problems, but no studies have examined the case of UV
      treatment. A pure culture of Microcystis aeruginosa PCC 7806 was exposed to
      monochromatic low-pressure or polychromatic medium-pressure UV lamps. Irradiated
      pure culture suspension was subsequently incubated for 14 days under white light
      fluorescent lamps. During incubation, profiles of the number of cells,
      intracellular and extracellular microcystin concentration were determined. After
      the UV exposure, the number of cells gradually diminished; the net log cell
      reduction after 6 days of incubation was 1.6 log or 2.0 log for 600 mJ/cm2 of LP
      or MP UV irradiation, respectively. There were three findings for UV irradiation
      effects on the release of intracellular microcystin. First, because UV exposure
      can inhibit increases in the number of cells for about 6 days, it inhibited the
      increase of microcystin concentrations in water. Second, intracellular
      microcystin was gradually released into the surrounding water through a gradual
      reduction in the number of cells, preventing a rapid increase of microcystin
      concentration in water. Microcystin concentration in water was not significantly
      higher in UV-irradiated samples than non-UV-irradiated sample. Third, UV
      irradiation was able to degrade intracellular microcystin; it was reduced from
      24.6 to 7.06 or 7.16 fg/cell by 600 mJ/cm2 of LP or MP UV irradiation,
      respectively. This contributed to reduce increases in microcystin concentrations
      in water. UV treatment can inhibit Microcystis growth and reduce intracellular
      microcystin content without rapid release of intracellular microcystin.

PMID- 17548105
TI  - Selected diseases and conditions associated with bovine conceptus loss in the
      first trimester.
AB  - The outcomes of insults to the bovine conceptus depend on the predilection of the
      insulting agent for the gravid reproductive tract, the virulence of the insult,
      and the developmental maturity/immune competence of the conceptus at the time of
      the insult. Agents that are lethal at one time during gestation may be harmless
      at another, or may have completely different effects (some not so harmless) at
      different gestational ages. This review discusses some of the known physical
      mechanical, physiological, and infectious causes of first trimester bovine
      conceptus losses, including three infectious agents that have been the subject of
      recent studies for their potential to transmit disease via embryo transfer.

PMID- 17548106
TI  - eFSH in clinical equine practice.
AB  - Equine follicle stimulating hormone (eFSH) has been used to induce follicular
      development in transitional mares and problem acyclic mares, as well as
      superovulate cycling mares. The most efficacious protocol is to administer 12.5
      mg eFSH, intramuscularly, twice daily beginning 5 to 7 days after ovulation when
      the diameter of the largest follicle is 20 to 25 mm. Prostaglandins are to be
      administered on the second day of eFSH therapy. Treatment with eFSH is continued
      for 3 to 5 days until follicle(s) are >or=35 mm in diameter. The mare is
      subsequently allowed to 'coast' for 36 h, after which human chorionic
      gonadotropin is administered to induce ovulation.

PMID- 17548107
TI  - Filter-feeder macroinvertebrates as key players in culturable bacteria
      biodiversity control: a case of study with Sabella spallanzanii (Polychaeta:
      Sabellidae).
AB  - The present study investigates the effect of the filtering activity of Sabella
      spallanzanii on the culturable heterotrophic bacterial community through the
      comparison of the bacterial diversity in transplanted polychaetes and the
      surrounding seawater. For isolation of culturable heterotrophic bacteria,
      seawater samples as well as polychaete homogenates were plated in triplicates
      onto Bacto Marine Agar 2216 (Difco). All the colonies grown were isolated,
      subcultured and identified by several morphological, biochemical and cultural
      methods. Some bacterial genera showed higher average abundances in polychaetes
      than in seawater (i.e. Lucibacterium and Photobacterium). Aeromonas represented a
      conspicuous component of the bacterial community both in S. spallanzanii and
      seawater. The presence of Cytophaga and Pseudomonas was also relevant in the
      examined seawater samples. The selective concentrations of some bacterial genera
      inside S. spallanzanii either by grazing on bacteria or their capability as
      bacterial reservoirs, provides evidence for the role of macrobenthic
      invertebrates as key determinants for microbial diversity.

PMID- 17548108
TI  - Evidence for a receptor-activated Ca2+ entry pathway independent from Ca2) store
      depletion in endothelial cells.
AB  - Ca(2+) entry in endothelial cells is a key signaling event as it prolongs the
      Ca(2+) signal activated by a receptor agonist, and thus allows an adequate
      production of a variety of compounds. The possible routes that lead to Ca(2+)
      entry in non-excitable cells include the receptor-activated Ca(2+) entry (RACE),
      which requires the presence of an agonist to be activated, and the store-operated
      Ca(2+) entry (SOCE) pathway, whose activation requires the depletion of the ER
      Ca(2+) store. However, the relative importance of these two influx pathways
      during physiological stimulation is not known. In the present study we
      experimentally differentiated these two types of influxes and determined under
      which circumstances they are activated. We show that La(3+) (at 10 microM) is a
      discriminating compound that efficiently blocks SOCE but is almost without effect
      on histamine-induced Ca(2+) entry (RACE). In line with this, histamine does not
      induce massive store depletion when performed in the presence of extracellular
      Ca(2+). In addition, inhibition of mitochondrial respiration significantly
      reduces SOCE but modestly affects RACE. Thus, agonist-induced Ca(2+) entry is
      insensitive to La(3+), and only modestly affected by mitochondrial
      depolarization. These data shows that agonist relies almost exclusively on RACE
      for sustained Ca(2+) signaling in endothelial cells.

PMID- 17548109
TI  - Antimicrobial activity of truncated alpha-defensin (human neutrophil peptide
      (HNP)-1) analogues without disulphide bridges.
AB  - Antimicrobial peptides play an important role in host defence, particularly in
      the oral cavity where there is constant challenge by microorganisms. The alpha
      defensin antimicrobial peptides comprise 30-50% of the total protein in the
      azurophilic granules of human neutrophils, the most abundant of which is human
      neutrophil peptide 1 (HNP-1). Despite its antimicrobial activity, a limiting
      factor in the potential therapeutic use of HNP-1 is its chemical synthesis with
      the correct disulphide topology. In the present study, we synthesised a range of
      truncated defensin analogues lacking disulphide bridges. All the analogues were
      modelled on the C-terminal region of HNP-1 and their antimicrobial activity was
      tested against a range of microorganisms, including oral pathogens. Although
      there was variability in the antimicrobial activity of the truncated analogues
      synthesised, a truncated peptide named 2Abz(23)S(29) displayed a broad spectrum
      of antibacterial activity, effectively killing all the bacterial strains tested.
      The finding that truncated peptides, modelled on the C-terminal beta-hairpin
      region of HNP-1 but lacking disulphide bridges, display antimicrobial activity
      could aid their potential use in therapeutic interventions.

PMID- 17548110
TI  - Non-small cell lung cancer cells produce a functional set of complement factor I
      and its soluble cofactors.
AB  - The complement system is important for protection from invading pathogens,
      removal of waste products and guidance of the immune response. Furthermore,
      complement can be also targeted to cancer cells. However, membrane-bound
      inhibitors over-expressed by certain types of tumor cells restrict the cytotoxic
      activity of complement. Herein we report that non-small cell lung cancer (NSCLC)
      cells produce soluble complement inhibitors factor I (FI) and C4b-binding protein
      (C4BP). FI is a serine protease capable of degrading the activated complement
      components C3b and C4b, whilst C4BP acts as its cofactor. Furthermore, NSCLC
      cells express membrane-bound regulators and shed membrane cofactor protein (MCP),
      which shares cofactor function with C4BP. Secretion of FI from NSCLC cells was
      higher than previously reported for any non-hepatic source and FI produced by
      these cells could efficiently support cleavage of C3b and C4b. In vitro
      functional assays revealed that additional FI significantly decreased C3
      deposition and complement-dependent lysis, particularly when cofactors were
      added. Our results demonstrate that soluble inhibitors produced by NSCLC cells
      may provide further protection from complement beyond the level ensured by
      membrane-bound inhibitors and, as such, contribute to the aggressive phenotype of
      these lung cancer cells.

PMID- 17548111
TI  - Preterm infants show reduced stress behaviors and activity after 5 days of
      massage therapy.
AB  - Preterm infants residing in an NICU were randomly assigned to a massage therapy
      or to a control group. The preterm infants in the massage therapy group received
      three 15-min massages each day for 5 consecutive days, with the massages
      consisting of moderate pressure stroking to the head, shoulders, back, arms and
      legs and kinesthetic exercises consisting of flexion and extension of the limbs.
      Infant stress behaviors and activity were recorded on the first and last day of
      the study. Preterm infants receiving massage therapy showed fewer stress
      behaviors and less activity from the first to the last day of the study. The
      findings suggest that massage has pacifying or stress reducing effects on preterm
      infants, which is noteworthy given that they experience numerous stressors during
      their hospitalization.

PMID- 17548112
TI  - Assessment of neonatal rat's activity by the automated registration of the animal
      entries in the squares of a testing arena.
AB  - Automated registration of neonatal rat entries in the squares of a testing
      chamber is suggested for the animal locomotion assessment. This method allows
      detection of paddling and pivoting activities that are not accompanied by forward
      movement of the animal. The proposed technique is also relatively insensitive to
      nonlocomotor changes in a pup's body position, such as breathing and shaking, and
      thus offers a selective detection of locomotor-related activity. The application
      of the method permits the evaluation of spontaneous and stimulated motor activity
      of neonatal rats using relatively short test duration and a minimal number of
      animals.

PMID- 17548113
TI  - Human sperm protein encyclopedia and alloantigen index: mining novel allo
      antigens using sera from ASA-positive infertile patients and vasectomized men.
AB  - Anti-sperm antibodies (ASA) are an important cause of immunological infertility.
      The objective of this study was to identify immunodominant sperm antigens
      recognized by anti-sperm antibodies (ASA) in serum samples of infertile men,
      women and vasectomized men. High-resolution two-dimensional gel electrophoresis
      was employed to separate human sperm proteins using isoelectric focusing (IEF) or
      nonequilibrium pH gradient electrophoresis (NEPHGE), followed by PAGE and Western
      blotting. Serum samples from five infertile male and five infertile female
      subjects that contained ASA as assayed by the immunobead binding test (IBT), were
      analyzed by Western blotting using NEPHGE gels followed by enhanced
      chemiluminescence (ECL) to identify the basic sperm antigens reactive to the
      sera. Serum samples from five fertile male and five fertile female subjects that
      were ASA-negative by IBT were used as controls. Serum samples from six
      vasectomized men collected before vasectomy and at different time intervals until
      6 months after vasectomy were analyzed by Western blotting using IEF gels. The
      ECL blots were analyzed to compare immunoreactivity between serum samples from
      fertile and infertile subjects and identify antigens unique to sera of the
      infertile subjects. Similarly, immunoreactivity between serum samples from pre-
      and post-vasectomy was compared to identify antigens unique to sera collected
      following vasectomy. Five allo-antigenic basic protein spots were recognized by
      sera from infertile males but not from fertile subjects. Five sperm iso-antigenic
      basic spots were recognized by infertile female subjects. Two among six of the
      vasectomized men's sera showed a difference in the Western blot profile 6 months
      after vasectomy, recognizing at least one new protein spot in each case when
      compared to pre-vasectomy sera. The acrosomal protein SP-10 was identified as an
      alloantigen recognized by a post-vasectomy serum. Molecular identities of the
      known allo- and iso-antigens identified in this study and in previous studies
      from this laboratory are reviewed and discussed.

PMID- 17548114
TI  - Microtia in Finland: comparison of characteristics in different populations.
AB  - OBJECTIVE: To compare the characteristics of microtia in Finland and in other
      populations. METHODS: Retrospective case series and patient questionnaire of 190
      microtia patients referred for reconstruction of the earlobe to the Helsinki
      University Central Hospital during the years 1980-2005. RESULTS: The prevalence
      in Finland is 4.34/10,000 and varied in other populations from 0.83 to
      17.4/10,000. Microtia is seen more in males (58%), as unilateral (88.4%), right
      sided (59.5%) and it is almost always associated with aural atresia or stenosis
      (93%). There is conductive hearing loss in 96% and sensorineural hearing loss in
      8% of the affected ears. 11% of the patients had congenital heart defects, and 5%
      had anomalies of extremities. CONCLUSIONS: There is variation in the prevalence
      and characteristics of microtia in different populations.

PMID- 17548115
TI  - Circular excision and purse-string suture technique in the management of facial
      hemangiomas.
AB  - Hemangiomas are the most common soft tissue tumors in infancy. Treatment options
      for hemangiomas are numerous. The scar after lenticular excision and linear
      closure is often unacceptable. Localized cutaneous infantile hemangioma acts like
      a tissue expander. Therefore, circular excision and purse-string suture technique
      are applicable for hemangioma at any stage. For 2-year period we have operated 14
      patients with hemangioma using circular excision and purse-string suture
      technique. In eight patients hemangioma was localized in the head and neck
      region. Two infants with large hemangioma of the face are presented in this
      article. One patient had hemangioma with ulceration resistant to conservative
      treatment. Second patient had giant hemangioma, which caused partial disturbation
      of visual axis. We applied circular excision and purse-string suture technique in
      both patients. The results were good, without any postoperative complications.

PMID- 17548116
TI  - Rapid subtyping of tick-borne encephalitis virus isolates using multiplex RT-PCR.
AB  - Tick-borne encephalitis virus, an emerging pathogen in several countries in
      Europe and Asia, has been divided into three subtypes (European, Siberian and Far
      Eastern). These subtypes are associated with different severities of the disease.
      For that reason, early determination of the subtype in a clinical sample or in
      ticks removed from a patient in areas of co-circulation of two or three subtypes
      is of high importance. The development of a simple method of multiplex RT-PCR for
      rapid and easy subtyping of tick-borne encephalitis virus isolates is reported to
      fill this requirement. The method is based on the unique combination of
      oligonucleotide primers hybridizing with subtype-specific "signature" positions
      of the sequence encoding the viral envelope protein. The developed multiplex RT
      PCR also appears to be a useful method in studies focused on the molecular
      epidemiology of tick-borne encephalitis virus.

PMID- 17548117
TI  - Viral RNA extraction for in-the-field analysis.
AB  - Retroviruses encode their genetic information with RNA molecules, and have a high
      genomic recombination rate which allows them to mutate more rapidly, thereby
      posting a higher risk to humans. One important way to help combat a pandemic of
      viral infectious diseases is early detection before large-scale outbreaks occur.
      The polymerase chain reaction (PCR) and reverse transcription-PCR (RT-PCR) have
      been used to identify precisely different strains of some very closely related
      pathogens. However, isolation and detection of viral RNA in the field are
      difficult due to the unstable nature of viral RNA molecules. Consequently,
      performing in-the-field nucleic acid analysis to monitor the spread of viruses is
      financially and technologically challenging in remote and underdeveloped regions
      that are high-risk areas for outbreaks. A simplified rapid viral RNA extraction
      method is reported to meet the requirements for in-the-field viral RNA extraction
      and detection. The ability of this device to perform viral RNA extraction with
      subsequent RT-PCR detection of retrovirus is demonstrated. This inexpensive
      device has the potential to be distributed on a large scale to underdeveloped
      regions for early detection of retrovirus, with the possibility of reducing viral
      pandemic events.

PMID- 17548118
TI  - A universal transgene silencing approach in baculovirus-insect cell system.
AB  - Baculovirus-insect cell system (BICS) is considered one of the most efficient
      eukaryotic gene expression systems. This system has also been used for producing
      different recombinant baculoviruses with increased insect toxicity as potential
      biopesticides. Establishing a universal gene silencing (UGS) system is very
      important due to the increasing number of studies using RNA interference (RNAi)
      with BICS. In this work, the enhanced green fluorescent protein (EGFP) was used
      as the RNAi consistent target sequence located downstream of a depressant insect
      neurotoxin gene, LqqIT2 used as a model of the gene of interest. Small
      interfering RNA (siRNA) and inverted repeats of EGFP gene (IR-EG) were examined
      in targeting the EGFP-LqqIT2 (EL)-fusion mRNA or LqqIT2-EGFP (LE)-bicistronic
      mRNA for degradation. Suppression efficiencies using these inducers were examined
      transiently and stably in uninfected and infected insect Sf9 cells. Moreover,
      RNAi showed persistence for 4 and 8 days in baculovirus-infected as well as
      uninfected Sf9 cells, respectively. Bicistronic RNA seems an efficient way to
      lower cost and effort of the gene silencing approach while maintaining the
      biological activity of the protein of interest when the RNAi is not in use.

PMID- 17548119
TI  - Novel recombinant ELISA assays for determination of type-specific IgG antibodies
      against HSV-1 and HSV-2.
AB  - The two novel Novagnost enzyme-linked immunosorbent assays (ELISA, Dade Behring)
      based on recombinant viral glycoprotein G were evaluated for determination of
      herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) IgG. ELISA and immunoblot
      procedures approved by the US Food and Drug Administration served as the
      reference for selecting different serum panels to be tested. The sensitivity and
      specificity of the novel assay for HSV-1 IgG were 93.1-98.0% and 99.3-100%,
      respectively, while the sensitivity and specificity of the novel assay for HSV-2
      IgG were 100% and 94.6-97.6%, respectively. Using Kappa statistics, the Kappa
      indices were computed at 0.93-0.98 for the HSV-1 assays and 0.92-0.96 for the HSV
      2 assays suggesting an almost perfect agreement between the novel ELISAs and the
      reference tests. In conclusion, the novel immunoassays for determination of HSV-1
      or HSV-2 IgG can be recommended for the reliable type-specific diagnosis of HSV
      infections.

PMID- 17548120
TI  - Treatment of hepatitis B virus-infected cells with alpha-glucosidase inhibitors
      results in production of virions with altered molecular composition and
      infectivity.
AB  - Trimming of the N-glycans attached to the envelope proteins of hepatitis B virus
      (HBV) is required in different steps of the viral life cycle. Inhibition of the
      host enzymes alpha-glucosidases, involved in the endoplasmic reticulum (ER)
      associated processing of the N-linked glycans, results in misfolding of the HBV
      envelope proteins, prevention of HBV secretion and accumulation of viral DNA
      within infected cells. However, the impact of these effects on HBV morphogenesis
      and infectivity of the viral particles that are still released from cells with
      inhibited alpha-glucosidase has not been addressed so far. Using N
      butyldeoxynojirimycin (NB-DNJ), a competitive inhibitor of the ER alpha
      glucosidases, we analyzed the role of these enzymes on HBV assembly and
      infectivity of the virions released from HepG2.2.2.15 cells. HBV secreted from
      drug-treated cells contained an envelope with altered composition of the
      disulfide-linked oligomers and no detectable middle (M) protein. These molecular
      changes had a significant effect on HBV infectivity, reducing it to 20% compared
      to controls, for the highest concentrations of NB-DNJ used. Our data show for the
      first time that an active alpha-glucosidase activity is crucial for production of
      infectious HBV and provide new insights into the controversial role of the M
      protein in this process.

PMID- 17548121
TI  - The history and economic impact on the functional fitness of elderly in the South
      Eastern region of Poland: a comparison with US citizens.
AB  - The present study was aimed at analyzing the socio-economic influence on
      functional fitness parameters, described by the Fullerton tests. A pool of 180
      women divided into six age groups (65-69, 70-74, 75-79, 80-84, 85-89 and 90-94
      years) was examined. They all were informed-consent participants. The results
      clearly show that low life standard in the early biological development has a
      significant impact on the functional fitness in all age groups. Comparison of our
      results with those described previously for the USA inhabitants revealed a
      considerably lower level of functional fitness for the Polish population than
      observed in the US.

PMID- 17548122
TI  - Design of a large-scale surface-aerated bioreactor for biomass production using a
      VOC substrate.
AB  - The design of a large-scale bioreactor for the production of bacterial biomass
      adapted to the biodegradation of volatile organic compounds was carried out. The
      bioreactor model used integrated the microbial kinetics and fluid dynamics
      described by the compartment model approach. The process conditions and kinetic
      parameters were adopted from the laboratory experimental study of (Leon, E.,
      Seignez, C., Adler, N., Peringer, P., 1999. Growth inhibition of biomass adapted
      to the degradation of toluene and xylenes in mixture in a batch reactor with
      substrates supplied by pulses. Biodegradation 10, 245-250). The performance of
      the pulsed-batch stirred bioreactor under surface aeration conditions was
      simulated for different mixing configurations and conditions such as the impeller
      diameter, number of impellers, stirring speed, and oxygen pressure. The
      simulations were used for the cost analysis which resulted in the optimal design
      of the bioreactor.

PMID- 17548123
TI  - Genome-wide search for susceptibility genes to type 2 diabetes in West Africans:
      potential role of C-peptide.
AB  - C-peptide is a substance that the pancreas releases into the circulation in
      equimolar amounts to insulin and has demonstrated important physiological effects
      which relate to the vascular field, in particular the microcirculation. For this
      analysis, we included 321 full and 36 half sibling pairs affected with type 2
      diabetes (T2D) from West Africa. A genome-wide panel of 390 tri-nucleotide and
      tetra-nucleotide repeats with an average distance of 8.9 cM was performed on a
      total of 691 persons. Variance components based on multipoint linkage approach as
      implemented in SOLAR were performed for log C-peptide. Significant linkage
      evidences were observed on 10q23 at D10S2327 with a LOD score of 4.04 (nominal p
      value=0.000008, empirical p-value=0.0004); and on 4p15 at D4S2632 with a LOD
      score of 3.48 (nominal p-value=0.000031, empirical p-value=0.0013). Other
      suggestive evidence of linkage were observed on 15q14 at D15S659 with a LOD score
      2.41 (nominal p-value=0.000435, empirical p-value=0.0068), and on 18p11 near
      D18S976 with a LOD score 2.18 (nominal p-value=0.000771 and empirical p
      value=0.0094). Interestingly, five positional candidate genes for diabetes and
      related complications are located in our linkage region (the pituitary adenylate
      cyclase activating polypeptide (PACAP in 18p11); the peroxisome proliferator
      activated receptor gamma coactivator 1 (PPARGC1 in 4p15); PTEN, PPP1R5, and IDE
      located in 10q23. In conclusion, we identified four major genetic loci (10q23,
      4p15, 15q14, and 18p11) influencing C-peptide concentration in West Africans with
      T2D.

PMID- 17548124
TI  - AIDS denial in Asia: dimensions and roots.
AB  - AIDS denial has long been viewed as the obstacle to forging effective response in
      many Asian countries. This article examines the dimensions and roots of this
      phenomenon. It identifies seven types of views, attitudes, or tendencies that can
      be described as denial, dissent, disagreements, or doubts. Three major factors
      underlying the AIDS denial are discussed. These are (1) historical impressions
      that STDs are Western diseases, (2) desire of some Asian leaders to forge Eastern
      points of view, and (3) long-held negative image towards the peoples or groups
      who happened to be at the front-line of the population groups exposed to the
      epidemic. The third factor is the most important source of denial. AIDS denial is
      not a new and isolated phenomenon but the one shaped by the global and historical
      institutions. Asian AIDS denial reflects the authoritarian and moralist
      grievances arising from the perceived deterioration of traditional moral order.

PMID- 17548125
TI  - Digital Butterworth filter for subtracting noise from low magnitude surface
      electromyogram.
AB  - This work presents a digital filter designed to delimitate the frequency band of
      surface electromyograms (EMG) and remove the mains noise and its harmonics,
      focusing the signal analysis during reduced muscle activity. A Butterworth filter
      was designed as the frequency-domain product of a second order, high-pass filter
      with cutoff frequency 10 Hz, an eighth order low-pass filter, with cutoff at 400
      Hz and six stop-band filters, second order, centered at the 60 Hz mains noise and
      its harmonics until 360 Hz. The resulting filter was applied in both direct and
      reverse directions of the signals to avoid phase distortions. The performance was
      evaluated with a simulated EMG signal with additive noise in multiples of 60 Hz.
      A qualitative assessment was made with real EMG data, acquired from 16 subjects,
      with age from 20 to 32 years. Subjects were positioned in orthostatic position
      during 21s, being only the last second analyzed to assure stationarity. EMG were
      collected by Ag/AgCl electrodes on right lateral gastrocnemius, amplified with
      gain 5000, filtered in the band from 10 Hz to 1 kHz, and thus digitized with
      2ksamples/s. The filter effectively removed the mains noise components, with
      attenuations greater than 96.6%. The attenuation of the simulated signal at
      frequencies below 15 Hz and at 60 Hz caused only a small reduction of total
      power, preserving the original spectrum. Thus, the filter resulted suitable to
      the proposed application.

PMID- 17548126
TI  - Surgical resection after gefitinib treatment in patients with lung adenocarcinoma
      harboring epidermal growth factor receptor gene mutation.
AB  - Gefitinib is the first approved epidermal growth factor receptor (EGFR) tyrosine
      kinase inhibitor (TKI) for the treatment of patients with advanced non-small cell
      lung cancer (NSCLC) who failed to respond to conventional chemotherapy. Gefitinib
      has fairly effective anti-tumour activity in patients with tumours harboring EGFR
      gene mutations. However, there has been no data about the preoperative gefitinib
      treatment in NSCLC patients. We reported here two cases of surgical resection of
      residual disease after dramatic response to gefitinib in patients with lung
      adenocarcinoma harboring EGFR gene mutation. Because both of our patients
      initially had advanced local tumour burden (bulky N2 disease), complete resection
      would not have been technically feasible. However, preoperative gefitinib
      treatment made it possible to achieve complete resection in both patients. We
      believe that clinical trials are required to evaluate the role of preoperative
      treatment of EGFR-TKIs in patients with locally advanced NSCLC harboring EGFR
      gene mutation.

PMID- 17548127
TI  - Phase II trial of carboplatin and paclitaxel in non-small cell lung cancer
      patients previously treated with chemotherapy.
AB  - The purpose of this phase II trial was to evaluate the efficacy and toxicity of
      carboplatin plus paclitaxel in the treatment of advanced non-small cell lung
      cancer (NSCLC) previously treated with chemotherapy. Patients with a performance
      status (PS) of 0 or 1 who had received one or two previous chemotherapy regimens
      for advanced NSCLC were eligible. Paclitaxel 200mg/m(2) was infused over 3h and
      followed by carboplatin (area under the curve 6) infusion over 1h, once every 3
      weeks. Thirty patients were enrolled. A complete response was observed in 1
      patient and a partial response in 10 patients, for an overall response rate of
      36.7%. The median time to progression was 5.3 months. The median survival time
      was 9.9 months, and the 1-year survival rate was 47%. Hematological toxicity in
      the form of grade 3/4 neutropenia occurred in 54%, but grade 3 febrile
      neutropenia developed in only 3%. Non-hematological grade 3 toxicities were less
      frequent. There were no treatment-related deaths. The combination of carboplatin
      plus paclitaxel is an active and well-tolerated regimen for the treatment of
      NSCLC patients who have previously been treated with chemotherapy and have a good
      PS.

PMID- 17548128
TI  - Use of performance feedback to increase healthcare worker hand-hygiene behaviour.

PMID- 17548129
TI  - Unsaturated fluoro-ketopyranosyl nucleosides: synthesis and biological evaluation
      of 3-fluoro-4-keto-beta-d-glucopyranosyl derivatives of N(4)-benzoyl cytosine and
      N(6)-benzoyl adenine.
AB  - The protected beta-nucleosides 1-(2,4,6-tri-O-acetyl-3-deoxy-3-fluoro-beta-d
      glucopyranosyl)-N(4)-benzoyl cytosine (2a) and 9-(2,4,6-tri-O-acetyl-3-deoxy-3
      fluoro-beta-d-glucopyranosyl)-N(6)-benzoyl adenine (2b), were synthesized by the
      coupling of peracetylated 3-deoxy-3-fluoro-d-glucopyranose (1) with silylated
      N(4)-benzoyl cytosine and N(6)-benzoyl adenine, respectively. The nucleosides
      were deacetylated and several subsequent protection and deprotection steps
      afforded the partially acetylated nucleosides of cytosine 7a and adenine 7b,
      respectively. Finally, direct oxidation of the free hydroxyl group at 4'-position
      of 7a and 7b, and simultaneous elimination reaction of the beta-acetoxyl group,
      afforded the desired unsaturated 3-fluoro-4-keto-beta-d-glucopyranosyl
      derivatives. These newly synthesized compounds were evaluated for their potential
      antitumor and antiviral activities. Compared to 5FU, the newly synthesized
      derivatives showed to be more efficient as antitumor growth inhibitors and they
      exhibited direct antiviral effect toward rotavirus.

PMID- 17548130
TI  - New glycosidic derivatives of histidine-containing dipeptides with antioxidant
      properties and resistant to carnosinase activity.
AB  - Synthesis, antioxidant properties and resistance to carnosinase hydrolysis of
      histidine-containing dipeptides are reported in this study. Carnosine (beta
      alanyl-l-histidine), homocarnosine (gamma-aminobutyryl-l-histidine) and anserine
      (beta-alanyl-3-methyl-l-histidine) were covalently derivatized with beta
      cyclodextrin to form different OH- or NH-bound conjugates. Mass spectroscopic and
      (1)H NMR data were used to determine the structure and the purity of the various
      beta-cyclodextrin derivatives. The inhibitory effect towards oxidation of human
      LDL induced by Cu(2+) ions, was estimated by measuring malondialdehyde formation
      as a function of increasing concentrations of these newly synthesized compounds
      (the beta-cyclodextrin-anserine conjugated in 3 had the highest antioxidant
      effect). All derivatives had higher antioxidant effects than those of the
      corresponding free histidine-containing dipeptides. Resistance to rat brain
      carnosinase hydrolysis of the most active derivatives indicated that these
      compounds are good candidates for further studies in more complex cellular and
      animal models. Their possible applications for remedies in neurodegenerative
      disorders, such as Alzheimer's and Parkinson's diseases, are discussed.

PMID- 17548131
TI  - Video streaming: implementation and evaluation in an undergraduate nursing
      program.
AB  - Video streaming technology enables video content, held on the web sites, to be
      streamed via the web. We report the implementation and evaluation of video
      streaming in an undergraduate nursing program in a metropolitan university in
      Australia. Students (n=703) were emailed a survey with a 15% response rate. We
      found that 91% (n=74) of respondents stated that video streaming assisted their
      learning. Forty-six percent(n=50) of students had difficulty accessing video
      streaming (particularly at the beginning of the study period). Over a 97-day
      period there were 8440 "hits" to the site from 1039 different internet protocol
      (IP) addresses. There were 4475 video streaming sessions undertaken by users.
      Video streaming was used for reviewing previously attended lectures (52%, n=56),
      examination preparation (34%, n=37), viewing missed lectures (27%, n=29) and
      class preparation (9%, n=10). Our experience with the introduction of video
      streaming has met with general enthusiasm from both students and teaching staff.
      Video streaming has particular relevance for rural students.

PMID- 17548132
TI  - Swelling at or near injection site: case definition and guidelines for
      collection, analysis and presentation of immunization safety data.

PMID- 17548134
TI  - Immunogenicity and in vitro protective efficacy of a polyepitope Plasmodium
      falciparum candidate vaccine constructed by epitope shuffling.
AB  - A polyepitope chimeric antigen incorporating multiple protective and conservative
      epitopes from multiple antigens of Plasmodium falciparum has been considered to
      be more effective in inducing multiple layers of immunity against malaria than a
      single stage- or single antigen-based vaccine. By modifying the molecular
      breeding approach to epitope shuffling, we have constructed a polyepitope
      chimeric gene that encodes 11 B-cell and T-cell proliferative epitope peptides
      derived from eight key antigens mostly in the blood stage of Plasmodium
      falciparum. A 35-kDa antigen encoded by this gene, named Malaria RCAg-1, was
      purified from an E. coli expression system. Immunization of rabbits and mice with
      the purified protein in the presence of Freund's adjuvant strongly generated long
      lasting antibody responses that recognized the corresponding individual epitope
      peptide in this vaccine as well as blood stage parasites. CD4(+) T-cell responses
      were also elicited as shown by the enhancement of T-cell proliferation, IFN-gamma
      and IL-4 level. In vitro assay of protection revealed that vaccine-elicited
      antibodies could efficiently inhibit the growth of blood-stage parasites.
      Additionally, the chimeric antigen was recognized by human serum specimens from
      malaria patients and individuals living in the endemic area. Our studies indicate
      the potential of M.RCAg-1 recombinant protein as malaria candidate vaccines as
      well as the rationale of the epitope shuffling technology applied in designing
      malaria vaccines.

PMID- 17548135
TI  - Cellulitis at injection site: case definition and guidelines for collection,
      analysis, and presentation of immunization safety data.

PMID- 17548136
TI  - The promise of conjugate vaccines for Africa.
AB  - Capsular polysaccharide (PS) vaccines against Neisseria meningitidis and
      Streptococcus pneumoniae have proven safe and effective. Moreover, experience
      with N. meningitidis, Haemophilus influenzae type b (Hib) and S. pneumoniae
      conjugate vaccines has demonstrated that immunogenicity of PS vaccines can be
      greatly improved by chemical conjugation to a protein carrier. These vaccines
      have been shown to stimulate B cell- and T cell-dependent immune responses, to
      induce immunological memory and to confer herd immunity. Their introduction has
      had a dramatic impact on the incidence of the diseases caused by these bacterial
      pathogens, but questions remain on the optimal schedules for immunization. The
      current schedule recommended by the World Health Organization (6, 10 and 14
      weeks) was developed in the early 1980s and does not take into consideration the
      crucial role of herd immunity in interrupting transmission. A review of the
      evidence in order to analyse how to optimize immunization schedules for conjugate
      vaccines is warranted.

PMID- 17548137
TI  - A single intranasal immunization with inactivated influenza virus and alpha
      galactosylceramide induces long-term protective immunity without redirecting
      antigen to the central nervous system.
AB  - alpha-Galactosylceramide (alpha-GalCer), originally isolated from a marine
      sponge, was known to activate natural killer T (NKT) cells through CD1d-mediated
      Ag presentation and induce Th1 and/or Th2 immunity. In this study, we evaluated
      the nasal adjuvanticity of alpha-GalCer when co-administered with formalin
      inactivated influenza virus A/PR/8/34 (PR8) in BALB/c mice. A single nasal
      immunization of inactivated PR8 and alpha-GalCer induced brisk levels of PR8
      specific IgG and IgA Abs in serum and lung washes. Antigen-specific Ab responses
      lasted for 3 months, providing protective immunity against challenge with live
      PR8. In addition, mice given alpha-GalCer also exhibited cellular immune
      responses including cytotoxic T lymphocyte (CTL) generation. Because it did not
      redirect Ags into brain, alpha-GalCer would likely pose no risk if administered
      as a nasal adjuvant. These results suggest for the first time that a single nasal
      immunization of inactivated virus and alpha-GalCer is a safe and effective means
      of preventing influenza infection.

PMID- 17548138
TI  - Safety of a trivalent meningococcal ACW135 vaccine among young children in
      Ethiopia.
AB  - A phase II open and parallel reactogenicity, immunogenicity and safety trivalent
      meningitis vaccine (Mencevax) trial was conducted on 413 volunteer 2-29-year-old
      rural residents in Ethiopia in November/December 2005. Adverse events (AE) were
      monitored at 1h, 1, 2, 3, 7 and 28 days after vaccination. No serious AE occurred
      except for burn injury (one) and severe malaria (one) after day 28. Irritability
      (45/411), loss of appetite (27/411), pain at injection site (26/412), dizziness
      (18/409), crying (14/411), insomnia, headache and diarrhoea (13/411) were the
      most frequent AEs. Overall, the vaccine is safe in the age groups studied.

PMID- 17548139
TI  - To what extent are hepatic concentrations of heavy metals in Anguilla anguilla at
      a site in a contaminated estuary related to body size and age and reflected in
      the metallothionein concentrations?
AB  - We explored how hepatic [metal]s in Anguilla anguilla at a contaminated estuarine
      site are influenced by body size, age and season, and the extent that [Cu], [Cd]
      and [Zn]s are reflected in [metallothionein (MT)]s. Although each [metal] and
      [MT] increased significantly with length, weight and age, those biotic variables
      explained <10% of the variation in each [metal] and only 11-16% for [MT].
      Seasonal changes in [Cu] and [Cd] were paralleled by [MT]. The variation in [MT]
      explained by Cu (42%) was greater than by Zn (16%) and Cd (13%), and seasonally
      lay between 43 and 69% for those metals collectively. Thus, hepatic [MT] in eels
      is closely correlated with hepatic [heavy metal]s. However, the great variability
      among [MT]s for eels of similar sizes and ages, which reflects marked variability
      in hepatic [heavy metal]s, means that this variable reflects imprecisely the
      contamination level at a particular site.

PMID- 17548140
TI  - The removal of Polycyclic Aromatic Hydrocarbons in the wastewater treatment
      process: experimental calculations and model predictions.
AB  - The removal of PAHs during the wastewater treatment process was examined in an
      activated sludge mode conventional facility. Concentrations reported are taken
      from an earlier measuring campaign. Removals of PAHs ranged between 28 and 67% in
      the primary, <1-61% in the secondary stage, and 37-89% in the whole process.
      Significant positive relationships were observed for removal efficiencies and the
      log K(ow) of PAHs in the primary and the log K(H) of PAHs in the secondary stage.
      Experimental removals were compared to those obtained from the FATE model. In the
      primary stage, predicted removals were lower than those experimentally calculated
      while in the secondary stage were higher. Predicted removals were apportioned
      mainly to sorption with negligible contribution from volatilization and
      biodegradation. Remarkable consistency between experimental and modeled removal
      efficiencies (-20-+20%) was observed for almost all PAHs in the whole treatment
      process.

PMID- 17548141
TI  - Anticipation of migration and psychological stress and the Three Gorges Dam
      project, China.
AB  - Findings from a prospective study of project-induced migration in China's Three
      Gorges Dam project are reported. The study tests the hypotheses that anticipation
      of involuntary migration is stressful and that the harmful effects are partially
      mediated and moderated by the resources migrants possess. Using data collected
      from a sample of designated migrants (n=975) who will be forced to relocate
      because they live in an area, which will be flooded once the Three Gorges project
      is completed, and non-migrants (n=555) in the same region, our analysis indicates
      that anticipation of involuntary migration is a robust predictor of mental
      distress. Anticipation of forced migration elevates depression (CES-D) not only
      directly, but also indirectly by weakening the social and the psychological
      resources (i.e., social support and mastery), which safeguard the mental well
      being of migrants. However, our results show much less support for the hypothesis
      that resources moderate harmful effects of forced migration.

PMID- 17548142
TI  - Catechins: natural free-radical scavengers against ochratoxin A-induced cell
      damage in a pig kidney cell line (LLC-PK1).
AB  - Besides aflatoxin B1, recent findings suggested that oxidative stress plays an
      important role in the toxicity of an other mycotoxin: ochratoxin A (OTA). The
      protective effect of two catechins (epigallocatechin gallate, EGCG, and
      epicatechin gallate, ECG) against OTA-induced cytotoxicity was investigated in a
      pig kidney cell line (LLC-PK1). The ability of the catechins to reduce ROS
      production and DNA fragmentation induced by OTA was also investigated. Our
      experiments proved the significant cytoprotective effects of the molecules in
      vitro from OTA-induced cell damage. In particular a 24h pre-treatment with EGCG
      or ECG restored cell viability with respect to OTA alone. Pre-treatment with EGCG
      at low concentration for 8 days protected cells from OTA-induced cell death.
      Moreover both catechins reduced OTA-induced ROS production. A reduction of OTA
      induced DNA fragmentation was found for LLC-PK1 cells pre-treated with EGCG and
      ECG. The free-radical scavenging capacity of both catechins was tested with the
      Briggs-Rauscher oscillating method (pH approximately 2) and the TEAC assay (pH
      7.4). The results show a good scavenging power according with inhibition of ROS
      production. Catechins could be useful to develop alimentary strategies for both
      humans and animals to prevent OTA-induced cytotoxicity.

PMID- 17548143
TI  - Clinical trial of G-Bond all-in-one adhesive and Gradia Direct resin composite in
      non-carious cervical lesions-results at 1 year.

PMID- 17548144
TI  - Application of strategies for sanitation management in wastewater treatment
      plants in order to control/reduce greenhouse gas emissions.
AB  - Greenhouse gases (GHG), basically methane (CH(4)), carbon dioxide (CO(2)) and
      nitrous oxide (N(2)O), occur at atmospheric concentrations of ppbv to ppmv under
      natural conditions. GHG have long mean lifetimes and are an important factor for
      the mean temperature of the Earth. However, increasing anthropogenic emissions
      could produce a scenario of progressive and cumulative effects over time, causing
      a potential "global climate change". Biological degradation of the organic matter
      present in wastewater is considered one of the anthropogenic sources of GHG. In
      this study, GHG emissions for the period 1990-2027 were estimated considering the
      sanitation process and the official domestic wastewater treatment startup
      schedule approved for the Metropolitan Region (MR) of Santiago, Chile. The
      methodology considers selected models proposed by the Intergovernmental Panel on
      Climate Change (IPCC) and some others published by different authors; these were
      modified according to national conditions and different sanitation and temporal
      scenarios. For the end of the modeled period (2027), results show emissions of
      about 65 Tg CO(2) equiv./year (as global warming potential), which represent
      around 50% of national emissions. These values could be reduced if certain
      sanitation management strategies were introduced in the environmental management
      by the sanitation company in charge of wastewater treatment.

PMID- 17548145
TI  - Designing environmental campaigns by using agent-based simulations: strategies
      for changing environmental attitudes.
AB  - Agent-based computer simulation was used to create artificial communities in
      which each individual was constructed according to the principles of the
      elaboration likelihood model of Petty and Cacioppo [1986. The elaboration
      likelihood model of persuasion. In: Berkowitz, L. (Ed.), Advances in Experimental
      Social Psychology. Academic Press, New York, NY, pp. 123-205]. Campaigning
      strategies and community characteristics were varied systematically to understand
      and test their impact on attitudes towards environmental protection. The results
      show that strong arguments influence a green (environmentally concerned)
      population with many contacts most effectively, while peripheral cues have the
      greatest impact on a non-green population with fewer contacts. Overall, deeper
      information scrutiny increases the impact of strong arguments but is especially
      important for convincing green populations. Campaigns involving person-to-person
      communication are superior to mass-media campaigns because they can be adapted to
      recipients' characteristics.

PMID- 17548146
TI  - A critical analysis of surgery for kidney cancer with vena cava invasion.
AB  - OBJECTIVE: Patients with kidney cancer with venous system involvement are at high
      risk of cancer recurrence even after the tumor thrombus is successfully removed.
      This review analyzes the impact on prognosis of the level of involvement of the
      inferior vena cava (IVC) in renal cell carcinoma (RCC). METHODS: A literature
      search was done and relevant papers were reviewed. Relatively recent papers as
      well as large series or papers from expert centers are included in the reference
      list. RESULTS: Venous invasion in RCC is a major challenge for urologists and
      patients with venous involvement have a worse prognosis. Although successful
      removal of a tumor thrombus in the renal vein and IVC may result in improved long
      term survival in more than half of the affected patients, a higher level of
      thrombus appears to be a bad prognosticator for cancer recurrence. A complete IVC
      thrombectomy, even in the metastatic setting, provides a better quality of life
      and may prolong survival. CONCLUSIONS: Because surgery still remains the most
      effective therapeutic option in patients wtih RCC, every attempt should be made
      to completely remove the IVC thrombus. New targeted agents could be promising as
      adjuvant therapy in this subset of patients.

PMID- 17548147
TI  - Assessment of luteinizing hormone receptor function in an endometrial cancer cell
      line, Ishikawa cells in response to human chorionic gonadotrophin (hCG).
AB  - Luteinizing hormone (LH) and human chorionic gonadotropin (hCG) play an important
      role in the development and maintenance of male and female gonads. Both these
      hormones act through the same specific receptor LH/hCG receptor (LHR). Recent
      studies have shown the existence of functional LHR in several non-gonadal
      tissues. The aim of this study was to confirm the functional existence of LHR in
      an endometrial adenocarcinoma cell line, Ishikawa cells, which has been used
      since long as an in vitro uterine endometrium model. Reverse transcriptase
      polymerase chain reaction (RT-PCR) data showed the stable expression of LHR in
      this cell line. However, the receptor failed to activate the PKA pathway in
      response to hCG, which is the most conventional mode of LH/hCG action in target
      tissues. When tested for other pathways, hCG failed to activate them either.
      Nested RT-PCR confirmed the existence of full-length LHR and this was further
      supported by Western blot. This study demonstrated that although Ishikawa cells
      do possess a full-length LHR, which was confirmed by RT-PCR, nested RT-PCR,
      Western blot and DNA sequencing, it failed to activate the conventional LH
      mediated downstream signaling. Based on these data we hypothesize that in
      Ishikawa cells LH/hCG does not utilize its conventional receptor. Whether it acts
      through some other receptor is a question, which can be answered through future
      research.

PMID- 17548148
TI  - A simple correlation for predicting heats of fusion of nitroaromatic carbocyclic
      energetic compounds.
AB  - In this paper, it is shown that heats of fusion of nitroaromatic carbocyclic
      energetic compounds can be predicted by using some structural parameters.
      Elemental composition and the contribution of some specific polar functional
      groups would be needed in the new method. Predicted heats of fusion using the
      method described herein for 41 nitroaromatic carbocyclic compounds are compared
      with experimental data. Calculated heats of fusion have a root mean square (rms)
      deviation of 3.01 kJ/mol and average deviation of 2.35 kJ/mol for these energetic
      compounds.

PMID- 17548149
TI  - Removal of lead, cadmium, zinc, and copper from industrial wastewater by carbon
      developed from walnut, hazelnut, almond, pistachio shell, and apricot stone.
AB  - In this work, adsorption of copper (Cu), zinc (Zn), lead (Pb), and cadmium (Cd)
      that exist in industrial wastewater onto the carbon produced from nutshells of
      walnut, hazelnut, pistachio, almond, and apricot stone has been investigated. All
      the agricultural shell or stone used were ground, sieved to a defined size range,
      and carbonized in an oven. Time and temperature of heating were optimized at 15
      min and 800 degrees C, respectively, to reach maximum removal efficiency. Removal
      efficiency was optimized regarding to the initial pH, flow rate, and dose of
      adsorbent. The maximum removal occurred at pH 6-10, flow rate of 3 mL/min, and
      0.1g of the adsorbent. Capacity of carbon sources for removing cations will be
      considerably decreased in the following times of passing through them. Results
      showed that the cations studied significantly can be removed by the carbon
      sources. Efficiency of carbon to remove the cations from real wastewater produced
      by copper industries was also studied. Finding showed that not only these cations
      can be removed considerably by the carbon sources noted above, but also removing
      efficiency are much more in the real samples. These results were in adoption to
      those obtained by standard mixture synthetic wastewater.

PMID- 17548150
TI  - Effects of ethylene on NO conversion and product distributions in an rf discharge
      reactor.
AB  - In the previous study, high concentration of NO in N(2)/O(2) mixtures could be
      converted mainly into N(2) via a radio-frequency discharge approach at a low
      pressure (4 kPa). To enhance the efficiency of NO removal, C(2)H(4) was added to
      elevate significantly the NO conversion in this study. The results showed that at
      inlet C(2)H(4)/NO molar ratio of 1 and 120 W in the C(2)H(4)/NO (1%)/O(2)
      (6%)/N(2) mixtures, the NO conversion reached 93.7% with a C(2)H(4) conversion of
      100%, to much higher than without C(2)H(4) condition (NO conversion=77.6%).
      Moreover, as high as 99.8% of the fraction of total N atoms converted from NO
      into N(2) was achieved. In addition, the relationship between the major active
      species observed in the optical emission spectra at different inlet C(2)H(4)
      concentration and the important reactions for NO removal and N(2) formation were
      discussed.

PMID- 17548151
TI  - COMT genotype and cognitive ability: a longitudinal aging study.
AB  - Dopaminergic neurotransmission in the pre-frontal cortex (PFC) contributes to
      individual cognitive differences in animals and humans. Catechol-O
      methyltransferase (COMT) influences dopamine concentration in the PFC. Functional
      variation in the human COMT gene occurs at a single nucleotide polymorphism (SNP)
      -472G>A--that results in a valine (Val) to methionine (Met) amino acid
      substitution (Val158Met). The Met/Met form is less active resulting in higher
      dopamine concentrations and thus may enhance cognitive function. We applied
      repeated measures mixed general linear modelling over three waves between ages 64
      and 68 years to optimise cognitive phenotype characterisation in a cohort of 473
      community volunteers who had validated childhood IQ data. After adjusting for
      childhood IQ, wave of testing and specific test type, COMT Val158Met genotype
      polymorphism had a significant overall effect on cognition (F(2,935.7)=7.92,
      p<.001) with adjusted means of all cognitive test scores taken together being:
      Val/Val 33.0 (95% C.I. 32.2-33.8), Val/Met 34.9 (95% C.I. 34.3-35.5), and Met/Met
      34.9 (95% C.I. 34.1-35.8). This study adds to the evidence that the Val/Val
      polymorphism has a detrimental effect on cognition, extending upwards the age
      range in which such an effect has been detected.

PMID- 17548152
TI  - Association between A218C polymorphism of the tryptophan-hydroxylase-1 gene, harm
      avoidance and binge eating behavior in bulimia nervosa.
AB  - Genes involved in serotonin transmission are likely involved in the biological
      predisposition to bulimia nervosa. We investigated whether the A218C polymorphism
      of the tryptophan-hydroxylase-1 gene was associated to bulimia nervosa and/or to
      some phenotypic aspects of the disorder. One hundred eighty Caucasian women (91
      patients with bulimia nervosa and 89 healthy controls) were enrolled into the
      study. They underwent a blood sample collection for A218C polymorphism of the
      tryptophan-hydroxylase-1 genotyping and a clinical evaluation assessing
      comorbidity for Axis I and II psychiatric disorders, harm avoidance personality
      dimension and bulimic symptoms. The distribution of both tryptophan-hydroxylase-1
      A218C genotypes and alleles did not significantly differ between patients and
      controls. Bulimic women with the AA genotype exhibited a more severe binge eating
      behavior and higher harm avoidance scores than those with CC genotype. These
      findings support the idea that tryptophan-hydroxylase-1 A218C polymorphism does
      not play a part in the genetic susceptibility to bulimia nervosa, but it seems to
      be involved in predisposing bulimic patients to a more disturbed eating behavior
      and higher harm avoidance.

PMID- 17548154
TI  - Mobile phone 'talk-mode' signal delays EEG-determined sleep onset.
AB  - Mobile phones signals are pulse-modulated microwaves, and EEG studies suggest
      that the extremely low-frequency (ELF) pulse modulation has sleep effects.
      However, 'talk', 'listen' and 'standby' modes differ in the ELF (2, 8, and 217Hz)
      spectral components and specific absorption rates, but no sleep study has
      differentiated these modes. We used a GSM900 mobile phone controlled by a base
      station simulator and a test SIM card to simulate these three specific modes,
      transmitted at 12.5% (23dBm) of maximum power. At weekly intervals, 10 healthy
      young adults, sleep restricted to 6h, were randomly and single-blind exposed to
      one of: talk, listen, standby and sham (nil signal) modes, for 30 min, at 13:30
      h, whilst lying in a sound-proof, lit bedroom, with a thermally insulated silent
      phone beside the right ear. Bipolar EEGs were recorded continuously, and
      subjective ratings of sleepiness obtained every 3 min (before, during and after
      exposure). After exposure the phone and base-station were switched off, the
      bedroom darkened, and a 90 min sleep opportunity followed. We report on sleep
      onset using: (i) visually scored latency to onset of stage 2 sleep, (ii) EEG
      power spectral analysis. There was no condition effect for subjective sleepiness.
      Post-exposure, sleep latency after talk mode was markedly and significantly
      delayed beyond listen and sham modes. This condition effect over time was also
      quite evident in 1-4Hz EEG frontal power, which is a frequency range particularly
      sensitive to sleep onset. It is possible that 2, 8, 217Hz modulation may
      differentially affect sleep onset.

PMID- 17548153
TI  - Electroacupuncture combined with clomipramine enhances antidepressant effect in
      rodents.
AB  - The present study was designed to evaluate the antidepressant effect of
      electroacupuncture (EA) and the potential additive or synergistic effects of EA
      and clomipramine (CLO, a tricyclic antidepressant) in the mouse forced swimming
      test (FST) and chronic mild stress (CMS) induced depression-model rats. The FST
      is an antidepressant screening procedure performed initially to observe the
      immediate effects of EA and/or CLO on the immobility time. CLO (2.5, 5, 10, 20
      and 60mg/kg intraperitoneally) were administered at 23, 6 and 1h respectively
      prior to each test. EA was given at the 'Bai-Hui' (Du 20) and unilateral 'An
      Mian' (EX 17) acupoints 1h before each test. Immobility time was significantly
      reduced by EA and CLO at 2.5, 5, 10, 20 or 60mg/kg, respectively. EA combined
      with 2.5mg/kg CLO exhibited additive effects on the immobility time. In addition,
      rats were exposed chronically (1st-11th week) to a variety of mild unpredictable
      stressors. Depressed mood and anhedonia were recognized as a decrease in sucrose
      intake in the CMS rats. CLO at 2.5, 5mg/kg and EA at the same acupoints and
      parameters were administrated on the CMS rats once every other day for 6 weeks
      (5th-11th week). The intake of 1% sucrose solution was reduced by CMS, which was
      restored to normal level after 6 weeks treatment with 5mg/kg CLO or EA combined
      with 2.5mg/kg CLO. However, neither the sucrose intake nor the sucrose preference
      in the depressive rats was significantly changed by the treatment with EA or
      2.5mg/kg CLO alone. These results demonstrated that EA combined with CLO at low
      doses has an additive or synergistic antidepressant action, and this combination
      may provide an effective strategy for depression management.

PMID- 17548155
TI  - Ginsenosides compound K and Rh(2) inhibit tumor necrosis factor-alpha-induced
      activation of the NF-kappaB and JNK pathways in human astroglial cells.
AB  - Ginsenosides, the main component of Panax ginseng, have been known for the anti
      inflammatory and anti-proliferative activities. In this study, we investigated
      the molecular mechanisms responsible for the anti-inflammatory effects of
      ginsenosides on activated astroglial cells. Among 13 different ginsenosides,
      intestinal bacterial metabolites Rh(2) and compound K (C-K) showed a significant
      inhibitory effect on tumor necrosis factor-alpha (TNF-alpha)-induced expression
      of intercellular adhesion molecule-1 in human astroglial cells. Pretreatment with
      C-K or Rh(2) suppressed TNF-alpha-induced phosphorylation of IkappaBalpha kinase
      and the subsequent phosphorylation and degradation of IkappaBalpha. Additionally,
      the same treatment inhibited TNF-alpha-induced phosphorylation of MKK4 and the
      subsequent activation of the JNK-AP-1 pathway. The inhibitory effect of
      ginsenosides on TNF-alpha-induced activation of the NF-kappaB and JNK pathways
      was not observed in human monocytic U937 cells. These results collectively
      indicate that ginsenoside metabolites C-K and Rh(2) exert anti-inflammatory
      effects by the inhibition of both NF-kappaB and JNK pathways in a cell-specific
      manner.

PMID- 17548156
TI  - High dopamine turnover in the brains of Sandy mice.
AB  - Schizophrenia is a chronic mental disorder and patients with this disease show
      positive and negative symptoms, cognitive dysfunction, and deficits in the
      processing of emotion. From previous studies, dopaminergic neurons are believed
      to be related to schizophrenic symptoms. Dysbindin (DTNBP1: dystrobrevin binding
      protein 1) gene is a susceptibility gene for schizophrenia, but the involvement
      of this gene in the dopaminergic tone remains unknown. In this paper, we studied
      regional contents of dopamine and its metabolite in the Sandy (Sdy) mouse which
      expresses no dysbindin protein. The brains of Sdy and wild-type (WT) mice were
      dissected into ten regions and dopamine (DA) and homovanillic acid (HVA) in each
      region were determined. DA contents were significantly lower in the cortex,
      hippocampus, and hypothalamus of Sdy mice than WT mice, while HVA contents showed
      no differences between the strains. Western blot analysis revealed there were no
      differences in the amount of tyrosine hydroxylase (TH) in the midbrain (MB) of
      both strains. The ratios of DA to HVA, which is an index of DA turnover, were
      higher in the cortex and the hippocampus, but not in the hypothalamus. These data
      demonstrate that DA turnover in the specific regions of the brain of the Sdy
      mouse was increased, and the Sdy mouse is a possible useful candidate animal for
      studying the pathogenic mechanism of schizophrenia.

PMID- 17548157
TI  - Oxidative stress parameters in unmedicated and treated bipolar subjects during
      initial manic episode: a possible role for lithium antioxidant effects.
AB  - Studies have proposed the involvement of oxidative stress and neuronal energy
      dysfunctions in the pathophysiology of bipolar disorder (BD). This study
      evaluates plasma levels of the oxidative/energy metabolism markers,
      thiobarbituric acid reactive substances (TBARS), superoxide dismutase (SOD),
      catalase (CAT), and neuron-specific enolase (NSE) during initial episodes of
      mania compared to controls in 75 subjects. Two groups of manic subjects
      (unmedicated n=30, and lithium-treated n=15) were age/gender matched with healthy
      controls (n=30). TBARS and antioxidant enzymes activity (SOD and CAT) were
      increased in unmedicated manic patients compared to controls. Conversely, plasma
      NSE levels were lower during mania than in the controls. In contrast, acute
      treatment with lithium showed a significant reduction in both SOD/CAT ratio and
      TBARS levels. These results suggest that initial manic episodes are associated
      with both increased oxidative stress parameters and activated antioxidant
      defenses, which may be related to dysfunctions on energy metabolism and
      neuroplasticity pathways. Antioxidant effects using lithium in mania were shown,
      and further studies are necessary to evaluate the potential role of these effects
      in the pathophysiology and therapeutics of BD.

PMID- 17548158
TI  - Serotonin transporter gene (5-Htt): association analysis with temporal lobe
      epilepsy.
AB  - Two functional polymorphisms, a 44bp insertion/deletion polymorphism in the 5'
      regulatory region and a variable number of tandem repeat polymorphisms in the
      second intron of the serotonin transporter gene (5-HTT), were previously
      identified and suggested to modulate transcription. The current study was
      designed to determine the contribution of these polymorphisms in the 5-HTT gene
      to susceptibility to temporal lobe epilepsy (TLE). Two hundred and seventy six
      patients with TLE, and 309 age- and sex-matched healthy controls from Calabria
      (Southern Italy) were studied. Patients and controls were genotyped using the
      WAVE TM DNA Fragment Analysis System for the insertion/deletion polymorphism in
      the promoter region (5-HTTLPR), and the GENESCAN TM System for the variable
      number tandem repeat (VNTR) in the second intron of the 5-HTT gene (5-HTTVNTR).
      The program UNPHASED was used to compare genotype, allele and haplotype
      frequencies between cases and controls, including age and gender as covariates in
      the model. No significant differences between cases and controls were observed
      for 5-HTTLPR, but a significant association was obtained for the 5-HTTVNTR
      polymorphism, both modeling genotypes (P-value=0.0145) or alleles (P
      value=0.0086). Patients with TLE showed lower frequencies of the 10 repeat at 5
      HTTVNTR than the controls (26.2% in patients versus 40.8% in controls). The
      frequency of homozygous individuals for the 10 allele was observed to be lower
      among patients than the controls (5.2% of patients were 10/10 versus 18.8% of
      controls). Haplotype analysis did not increase the evidence for association.
      These results suggest that the serotonin transporter gene may play a role in the
      etiology of TLE.

PMID- 17548159
TI  - Production of neurospheres from mammalian Muller cells in culture.
AB  - In lower vertebrates, like fishes and amphibians, retina is able to self
      regenerate whereas Mammalian retina has lost this property. Nevertheless,
      recently, it has turned out that retinal glial Muller cells were playing a role
      in neuronal regeneration of the adult rodent retina, in case of acute damages, by
      dedifferentiating and redifferentiating in glial and neural cells. The purpose of
      this study was to analyse the ability of mammalian Muller cells for forming
      neurospheres. First of all, rats Muller cells were isolated in a primary culture.
      Second, these cells were resuspended in two different culture media: the cells
      cultures in the Neurobasal-A medium kept a typical Muller cells morphology even
      after 15 days of EGF treatment, and the cells plated in the DMEM-F12 medium
      formed neurospheres from the third day in culture. The neurosphere cells
      expressed nestin, cellular retinaldehyde binding protein (CRALBP) and glial
      fibrillary acidic protein (GFAP). These results showed our capacity to isolate
      and propagate Muller cells-derived progenitor cells. Moreover, it allows us to
      control the number of progenitor cells and, in the future, to study their
      differentiation capacity.

PMID- 17548160
TI  - Differential engagement of anterior cingulate and adjacent medial frontal cortex
      in adept meditators and non-meditators.
AB  - This study investigated differences in brain activation during meditation between
      meditators and non-meditators. Fifteen Vipassana meditators (mean practice: 7.9
      years, 2h daily) and fifteen non-meditators, matched for sex, age, education, and
      handedness, participated in a block-design fMRI study that included mindfulness
      of breathing and mental arithmetic conditions. For the meditation condition
      (contrasted to arithmetic), meditators showed stronger activations in the rostral
      anterior cingulate cortex and the dorsal medial prefrontal cortex bilaterally,
      compared to controls. Greater rostral anterior cingulate cortex activation in
      meditators may reflect stronger processing of distracting events. The increased
      activation in the medial prefrontal cortex may reflect that meditators are
      stronger engaged in emotional processing.

PMID- 17548161
TI  - Interaction of fibroblast growth factor 2 (FGF2) and notch signaling components
      in inhibition of oligodendrocyte progenitor (OP) differentiation.
AB  - Oligodendrocyte progenitor (OP) cell differentiation is a critical process of
      developmental myelination, tumor formation, and remyelination in the CNS.
      Activation of the fibroblast growth factor 2 (FGF2) or notch pathway can inhibit
      differentiation of OP cells. The current study examines the interaction of FGF2
      and notch signaling components in regulating OP differentiation. Cultured
      neonatal rat brain OP cells were used for transfection-based promoter assays and
      for infection with retroviruses expressing a GFP reporter to monitor OP
      differentiation into oligodendrocytes or astrocytes. FGF2 treatment resulted in a
      four-fold increase of transcriptional activity from the promoter region of Hes5,
      a notch pathway target gene. FGF2 inhibition of OP differentiation into
      oligodendrocytes was perturbed by retroviral expression of a dominant negative
      construct for mastermind-like 1, which is an important co-activator of
      transcription for notch target genes. OP differentiation into oligodendrocytes
      was reduced by co-culture with fibroblasts expressing Jagged1, a ligand for notch
      receptors. This Jagged1 inhibition of OP differentiation was not altered by
      retroviral expression of a dominant negative FGF receptor construct. Constitutive
      activation of notch signaling, by retroviral expression of the Notch1
      intracellular domain, greatly reduced OP differentiation into either
      oligodendrocytes or astrocytes and did not require FGF2 signaling. These findings
      indicate that inhibition of OP differentiation through the Notch1 pathway was not
      influenced by FGF2 signaling. However, FGF2 signaling may interact with down
      stream components of the notch signaling pathway, including mastermind-like1 and
      Hes5, to inhibit OP differentiation into oligodendrocytes.

PMID- 17548162
TI  - Characterization of the anticonvulsant profile of isonicotinic acid benzylamide
      in various experimental seizure models in mice.
AB  - This study focused on the evaluation of anticonvulsant properties of isonicotinic
      acid benzylamide (iso-Nic-BZA) in numerous experimental seizure models (maximal
      electroshock [MES]-, bicuculline [BIC]-, pentylenetetrazole [PTZ]-, pilocarpine
      [PILO]-, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid [AMPA]-, kainic
      acid [KA]- and N-methyl-d-aspartic acid [NMDA]-induced seizures). Moreover, acute
      adverse-effect profile of the agent with respect to impairment of motor
      coordination was assessed in animals subjected to the chimney test. The
      evaluation of time-course and dose-response relationships for iso-Nic-BZA
      provided evidence that the compound produced the peak to maximum antielectroshock
      action and acute adverse effects at 5min after its systemic (i.p.)
      administration. Iso-Nic-BZA exerted a clear-cut anticonvulsant action against
      maximal electroshock-induced seizures in mice and its ED(50) value was 70.6 (56.4
      88.4)mg/kg. The assessment of acute adverse effects in the chimney test revealed
      that the agent produced acute neurotoxic effects and its TD(50) value was 135.6
      (108.8-169.0)mg/kg. Additionally, iso-Nic-BZA showed the anticonvulsant activity
      in numerous chemically-induced seizures (AMPA-, BIC-, KA-, and PTZ-evoked clonic
      convulsions), remaining virtually ineffective (at doses up to 200mg/kg) in PILO-
      and NMDA-induced seizures in mice. Based on this study, one can conclude that iso
      Nic-BZA due to the short time to peak of its maximum anticonvulsant effects (5min
      after its i.p. administration), deserves more attention as a potential
      antiepileptic drug for patients in status epilepticus.

PMID- 17548163
TI  - Inhibition of nitric oxide synthase increases synaptophysin mRNA expression in
      the hippocampal formation of rats.
AB  - Synaptophysin is a protein involved in the biogenesis of synaptic vesicles and
      budding. It has been used as an important tool to investigate plastic effects on
      synaptic transmission. Nitric oxide (NO) can influence plastic changes in
      specific brain regions related to cognition and emotion. Experimental evidence
      suggests that NO and synaptophysin are co-localized in several brain regions and
      that NO may change synaptophysin expression. Therefore, the aim of the present
      work was to investigate if inhibition of NO formation would change synaptophysin
      mRNA expression in the hippocampal formation. Male Wistar rats received single or
      repeated (once a day for 4 days) i.p. injections of saline or l-nitro-arginine (l
      NOARG, 40mg/kg), a non-selective inhibitor of nitric oxide synthase (NOS). Twenty
      four hours after the last injection the animals were sacrificed and their brains
      removed for 'in situ' hybridization study using (35)S-labeled oligonucleotide
      probe complementary to synaptophysin mRNA. The results were analyzed by
      computerized densitometry. Acute administration of l-NOARG induced a significant
      (p<0.05, ANOVA) increase in synaptophysin mRNA expression in the dentate gyrus,
      CA1 and CA3. The effect disappeared after repeated drug administration. No change
      was found in the striatum, cingulated cortex, substantia nigra or nucleus
      accumbens. These results reinforce the proposal that nitric oxide is involved in
      plastic events in the hippocampus.

PMID- 17548164
TI  - Expression of transcription factors CREB and c-Fos in the brains of terminal
      Creutzfeldt-Jakob disease cases.
AB  - Expression levels and localization of transcription factors cAMP response element
      binding protein (CREB(1) and CREB(2)) and c-Fos, as well as levels of up-stream
      mitogen-activated protein kinases/extracellular signal-regulated kinases (ERK-1
      and ERK-2) and p38 kinase, were examined in the brains (frontal cortex) of eleven
      cases with Creutzfeldt-Jakob disease (CJD) and five age-matched controls.
      Preserved expression levels of ERK-1-P, ERK-2-P and p38-P were observed in CJD.
      However, significantly reduced levels, as revealed by gel electrophoresis and
      Western blotting, and reduced numbers of immunoreactive nuclei, as seen by
      immunohistochemistry, to CREB, CREB-P, c-Fos and c-Fos-P were found in CJD when
      compared with controls. These observations point to exhausted CREB and c-Fos
      brain responses, in spite of preserved up-stream signaling kinases, thus favoring
      cell death in terminal stages of CJD.

PMID- 17548165
TI  - Comparative study of skin grafting with and without surgical removal of
      granulation tissue in chronic burn wounds.
AB  - A prospective comparative study of skin grafting of chronic wounds with and
      without surgical removal of granulation tissue was done on 51 patients with an
      objective of finding a better method of skin grafting objectively in the chronic
      burns wounds. Comparative study was done on those patients who had wounds on both
      the sides of their body. Wounds present on the right side of the body labeled as
      Group A were skin grafted after removal of granulation tissue and wounds present
      on left side of the body labeled as Group B were skin grafted without removal of
      granulation tissue. There was no significant difference in the comparative
      bacteriology, graft uptake and cosmetic appearance of the grafts. We found no
      effect of bacteriology and chronicity of the wounds on the uptake of grafts in
      the two groups. Serum albumin levels <4 g% was found to be associated with
      statistically significant decreased graft uptake only in Group A wounds. It was
      further observed that Group A wounds were associated with more blood loss, less
      secure haemostasis, prolonged surgical duration and thus more cost of surgery as
      compared to Group B wounds.

PMID- 17548166
TI  - Bioinformatics analysis of diabetic retinopathy using functional protein
      sequences.
AB  - Diabetic retinopathy is the leading cause of blindness among patients with
      diabetes mellitus. We evaluated the role of several proteins that are likely to
      be involved in diabetic retinopathy by employing multiple sequence alignment
      using ClustalW tool and constructed a phylogram tree using functional protein
      sequences extracted from NCBI. Phylogram was constructed using Neighbor-Joining
      Algorithm in bioinformatics approach. It was observed that aldose reductase and
      nitric oxide synthase are closely associated with diabetic retinopathy. It is
      likely that vascular endothelial growth factor, pro-inflammatory cytokines,
      advanced glycation end products, and adhesion molecules that also play a role in
      diabetic retinopathy may do so by modulating the activities of aldose reductase
      and nitric oxide synthase. These results imply that methods designed to normalize
      aldose reductase and nitric oxide synthase activities could be of significant
      benefit in the prevention and treatment of diabetic retinopathy.

PMID- 17548167
TI  - PPAR gamma agonists can be expected to potentiate the efficacy of metronomic
      chemotherapy through CD36 up-regulation.
AB  - The ability of metronomic chemotherapy to induce endothelial apoptosis has been
      traced to increased endothelial expression of thrombospondin-1, which activates
      endothelial CD36 receptors, triggering the extrinsic apoptotic pathway.
      Endothelial expression of CD36 is variable. Recent studies show that PPAR gamma
      agonists - previously shown to have angiostatic activity - can markedly boost
      endothelial expression of CD36, thereby potentiating the apoptotic response of
      endothelial cells to thrombospondin-1-mimetic peptides. Thus, concurrent
      administration of PPAR gamma agonists would be expected to enhance the efficacy
      of metronomic chemotherapy. These considerations may help to rationalize recent
      reports that a regimen consisting of low-dose trofosfamide, pioglitazone, and a
      cox-2 inhibitor achieves tumor regression or prolonged tumor stasis in a
      meaningful proportion of cancer patients. The angiostatic efficacy of metronomic
      chemotherapy complemented by PPAR gamma agonist administration would likely be
      potentiated by ancillary measures that block the survival signals evoked by
      endothelial growth factors such as VEGF or angiopoietin-1.

PMID- 17548168
TI  - Combined transplantation of neural stem cells and olfactory ensheathing cells for
      the repair of spinal cord injuries.
AB  - Spinal cord repair is a problem that has long puzzled neuroscientists. The
      failure of the spinal cord to regenerate and undergo reconstruction after spinal
      cord injury (SCI) can be attributed to secondary axonal demyelination and
      neuronal death followed by cyst formation and infarction as well as to the nature
      of the injury environment, which promotes glial scar formation. Cellular
      replacement and axon guidance are both necessary for SCI repair. Multipotent
      neural stem cells (NSCs) have the potential to differentiate into both neuronal
      and glial cells and are, therefore, likely candidates for cell replacement
      therapy following SCI. However, NSC transplantation alone is not sufficient for
      spinal cord repair because the majority of the NSCs engrafted into the spinal
      cord have been shown to differentiate with a phenotype which is restricted to
      glial lineages, further promoting glial scaring. Olfactory ensheathing cells
      (OECs) are a unique type of glial cell that occur both peripherally and centrally
      along the olfactory nerve. The ability of olfactory neurons to grow axons in the
      mature central nervous system (CNS) milieu has been attributed to the presence of
      OECs. It has been shown that transplanted OECs are capable of migrating into and
      through astrocytic scars and thereby facilitating axonal regrowth through an
      injury barrier. Given the complementary properties of NSCs and OECs, we predict
      that the co-transplantation of NSCs and OECs into an injured spinal cord would
      have a synergistic effect, promoting neural regeneration and functional
      reconstruction. The lost neurocytes would be replaced by NSCs, while the OECs
      would build "bridges" crossing the glial scaring that conduct axon elongation and
      promote myelinization simultaneously. Furthermore, the two types of cells could
      first be seeded into a bioactive scaffold and then the cell seeded construct
      could be implanted into the defect site. We believe that this type of treatment
      would lead to improved neural regeneration and functional reconstruction after
      SCI.

PMID- 17548169
TI  - Dystonia redefined as central non-paretic loss of control of muscle action: a
      concept including inability to activate muscles required for a specific movement,
      or 'negative dystonia'.
AB  - Dystonia is defined as a syndrome of sustained muscle contractions, frequently
      causing twisting and repetitive movements, or abnormal postures. Although this
      definition comprises an essential feature of dystonia, the clinical observation
      indicates that there is an additional aspect of dystonia; failure to adequately
      activate muscles required for specific movement, exemplified by the lack of
      contractions of the levator palpebrae superioris muscles in apraxia of lid
      opening, as well as by inability to activate appropriate muscles in cervical
      dystonia or in the paretic form of writer's cramp, and possibly by dropped head
      syndrome or camptocormia seen in parkinsonian patients without apparent truncal
      dystonia or rigidity. Taking this "negative dystonia" into consideration, the
      author proposes a revised definition of dystonia as a symptom characterized by
      the central non-paretic loss of voluntary control of muscle activities, which may
      result in either excessive or deficient contractions of muscles, frequently
      causing twisting and repetitive movements, limitation of movements, or abnormal
      postures.

PMID- 17548170
TI  - Glatiramer acetate could be a potential therapeutic agent for Parkinson's disease
      through its neuroprotective and anti-inflammatory effects.
AB  - Parkinson's disease (PD) is the second most common neurodegenerative disease
      after Alzheimer's disease. The hallmark pathologic feature of PD is dopamine
      deficiency, caused by the degeneration of nigrostriatal dopaminergic neurons.
      Current treatments for PD mainly address the dopaminergic features of the
      disease; however they do not modify the progression of neurodegeneration. The
      need for newer and more effective agents is consequently receiving a great deal
      of attention. Brain-derived neurotrophic factor (BDNF), a member of the
      neurotrophic factor family, can promote survival of injured dopaminergic
      nigrostriatal neurons in the rodent. Postmortem studies have suggested that BDNF
      deficiency may play a role in PD pathogenesis. This is further supported by the
      finding that BDNF administration has a therapeutic effect in animal models of PD.
      Glatiramer acetate (GA) is a collection of synthetic polypeptides approved for
      the treatment of relapsing-remitting multiple sclerosis. Preclinical studies have
      demonstrated that peripheral GA administration can enhance central BDNF activity
      and augment neurogenesis. Furthermore, PD has been associated with an
      inflammatory process in the brain. Animal studies have demonstrated that GA
      administration has a central anti-inflammatory effect through the release of anti
      inflammatory cytokines. From the above evidence, GA could act as a potential
      therapeutic agent for PD by increasing central BDNF and by exerting an anti
      inflammatory effect. With the recent finding that GA administration can prevent
      neuronal loss and cognitive decline in Alzheimer's disease double-transgenic
      mice, early GA treatment may also prevent neurodegeneration and manifestations of
      PD symptoms in subjects with familial Parkinson's disease.

PMID- 17548171
TI  - Non-hypoxic preconditioning of myocardium against postoperative atrial
      fibrillation: mechanism based on enhancement of the antioxidant defense system.
AB  - Oxidative stress underlies postoperative atrial fibrillation and
      electrophysiological remodelling associated with rapid atrial pacing. An
      increasing body of evidence indicates that the formation of reactive oxygen
      species (ROS) released following extracorporeal circulation are involved in the
      structural and functional myocardial impairment derived from the ischemia
      reperfusion cycle. ROS behave as intracellular messengers mediating pathological
      processes, such as inflammation, apoptosis and necrosis, thereby participating in
      the pathophysiology of atrial fibrillation. Thus, increased superoxide (O(2)(.-))
      production has been found in isolated atrial cardiomyocytes from patients with
      atrial fibrillation. Therefore, it seems reasonable to assume that the
      reinforcement of the antioxidant defense system should protect the heart against
      functional alterations in the cardiac rhythm. On this line, antioxidant enzyme
      induction through in vivo exposure to moderate concentration of ROS is associated
      with a reduction in the susceptibility of myocytes to ROS-induced injury. This
      response could be due to a prevailing effect of survival over apoptotic pathway.
      Previously, tissue preconditioning caused by prior exposure to an
      ischemia/reperfusion cycle has been successfully applied in experimental models
      and clinical settings associated with oxidative damage by ROS. However, such
      hypoxic preconditioning method is harmful to be applied to many clinical
      conditions associated with oxidative stress. In turn, experimental studies have
      revealed that non-enzymatic antioxidants produce a significant functional
      amelioration in cardiomyocytes subjected to an oxidative challenge. Moreover,
      clinical studies with patients scheduled for primary coronary artery bypass graft
      surgery had a reduced incidence of postoperative atrial fibrillation. We present
      the hypothesis of non-hypoxic preconditioning based on the association of
      pretreatment with n-3 polyunsaturated fatty acids followed by ascorbate plus
      alpha-tocoferol supplementation diminishes the incidence of postoperative atrial
      fibrillation in patients subjected to cardiac surgery with extracorporeal
      circulation.

PMID- 17548172
TI  - Schedule-induced polydipsia alters cocaine- but not ethanol-induced suppression
      of saccharin consumption.
AB  - Under traditional water-deprived conditions, both LiCl and morphine produce
      comparable suppression of saccharin consumption after repeated pairings. However,
      under conditions of spaced food deliveries (i.e., schedule-induced polydipsia;
      SIP), morphine produces a significantly weaker suppression than LiCl. The
      differential responses have been attributed to an increase in the rewarding
      effects of drugs of abuse (such as morphine) that masked the expression of the
      aversive effects, a masking not evident with LiCl which has no reported rewarding
      effects. The present study extended this characterization to two additional drugs
      of abuse; cocaine and ethanol. Following schedule-induced saccharin consumption,
      female Sprague-Dawley rats were given injections of LiCl, cocaine, ethanol (at
      doses comparably effective in conditioning taste aversions under water
      deprivation) or distilled water vehicle. Although cocaine and ethanol both
      suppressed SIP, only cocaine produced a significantly delayed suppression
      relative to LiCl. The differential effects of cocaine (and morphine), but not
      ethanol, may be a function of the different reward profiles of these drugs. Given
      the differential ability of drugs of abuse to suppress consumption under
      conditions of spaced feedings, the SIP procedure may be a useful baseline to
      assess the rewarding effects of such drugs. Further, given the differential
      results with cocaine and ethanol, the relative rewarding effects of drugs may be
      differentially indexed in this preparation, as well.

PMID- 17548173
TI  - Heterologous expression of FMDV immunodominant epitopes and HSP70 in P. pastoris
      and the subsequent immune response in mice.
AB  - Mycobacterium tuberculosis heat shock protein70 (HSP70) is a major antigen with
      both chaperone and cytokine functions. It has been used as an adjuvant to induce
      or potentiate humoral and cellular immunity, both in the form of a mixture with
      peptide antigens, and as a fusion protein. We have evaluated the effects of HSP70
      on foot and mouth virus (FMDV) subunit vaccines. FMDV VP1, and a synthetic multi
      epitope FMDV (EG), and VP1-HSP70 and EG-HSP70 fusion proteins were all
      heterologously expressed in the yeast Pichia pastoris, and used as antigen in
      mice. The recombinant VP1 and EG alone was able to induce both humoral and
      marginal cell-mediated immune responses, while the HSP70 fusions markedly
      enhanced both the humoral and cell-mediated immune responses. The most prominent
      immune responses arose from vaccination with the EG-HSP70 fusion product. Both
      fusion protein-induced Th1-like cytokine (IFN-gamma) and Th2-like cytokine (IL-4)
      were identified.

PMID- 17548174
TI  - Dysfunctional cognitions in idiopathic environmental intolerances (IEI)--an
      integrative psychiatric perspective.
AB  - Idiopathic environmental intolerances (IEI) - formerly multiple chemical
      sensitivities (MCS) - are characterized by diffuse symptoms reported after
      exposure to low doses of everyday chemicals. Previous theories about the origin
      of IEI have emphasized either biological or psychological factors, neglecting a
      probable interplay. Many have suggested classifying IEI as a somatoform or an
      anxiety disorder, irrespective of some incongruities. By focusing on
      dysfunctional cognitions we discuss obvious parallels of IEI with somatoform
      disorders, and also indicate overlaps with anxiety and delusional disorders. To
      propose a hypothetical psycho-neurobiological basis of IEI, recent evidence about
      cortically represented symptoms in the absence of peripheral stimuli is briefly
      summarized. We conclude that IEI can serve as an illustrative example for the
      impact of cognitive, representational processes in symptom generation.

PMID- 17548175
TI  - LH response of seasonally anovular Corriedale ewes acutely exposed to rams and
      estrous ewes.
AB  - Serial blood sampling before and after exposing four anovular Corriedale ewes to
      a group of rams and estrous ewes during the non-breeding season revealed a
      pattern of LH secretion similar to that previously observed in Merinos. Mean LH
      values doubled (P<0.001) from 0.24+/-0.06 microgL(-1) (mean+/-s.e.m.) before to
      0.55+/-0.05 microgL(-1) after 2h of visual, auditory, and odor exposure to rams
      and estrous ewes in an indoor facility. A non-significant (P<0.17) increase of LH
      pulses per hour was also observed (0.7+/-0.3 pulses per hour before compared with
      1.3+/-0.3 during stimulation). All four ewes had recently formed corpora lutea by
      five days after stimulation. Results are consistent with the pattern of sudden
      increase and sustained release of LH observed in other sheep breeds, particularly
      the Merino.

PMID- 17548176
TI  - The effect of a combination of permanent breeding cage and low housing density on
      the reproductive success of farmed blue foxes.
AB  - Social factors are known to affect the reproduction of many canids both in the
      wild and in farms. For example, reproduction in farmed silver foxes is regulated
      by social stress; foxes seem to benefit from noncramped housing conditions and
      permanent breeding cages. However, no comparable studies have been carried out in
      farmed blue foxes. The aim of our experiment was to create an alternative,
      improved, economically viable and practical housing solution for blue foxes.
      Therefore, we compared reproductive performance of blue foxes in permanent
      breeding cages with low animal densities (L group, N=79) and traditional housing
      with its changing social environment with high animal density (H group, N=74).
      The reproductive data from the L and H groups were compared separately for
      primiparous and multiparous vixens because the reproductive performance in
      primiparous vixens was substantially lower (P<0.001) than in multiparous vixens.
      Altogether, 41 and 39% of the primiparous vixens in the H and L group whelped
      (P>0.05), but only 28 and 34%, respectively, weaned at least one cub (P>0.05),
      i.e., 72 and 66% of the primiparous vixens did not reproduce in the H and L
      group, respectively (P>0.05). The total reproductive performance, expressed as
      cubs at weaning per breeding female, was 1.7+/-3.5 for the H and 1.6+/-2.9 for
      the L group (P>0.05). In the primiparous vixens, the only statistically
      significant difference observed between the two housing systems was that the
      onset of oestrus occurred five days earlier in the H than in the L group
      (P<0.05). All multiparous vixens in the L group exhibited oestrus compared to 94%
      in the H group (P>0.05). Furthermore, there was a nonsignificant (ns) trend for
      fewer barren females (9% versus 17%), more successfully reproducing vixens (83%
      versus 74%) and a higher number of live-born cubs (10.9+/-4.7 versus 9.4+/-3.9)
      in the L than in H group in the multiparous vixens (for all P>0.05). This
      resulted in 1.7 and 1.4 cubs more per breeding and per mated vixen, respectively,
      at weaning in the L group (7.3+/-5.0) compared to the H group (5.6+/-4.2), but
      also this difference was nonsignificant. Although our present results lack
      statistical significance, they are promising enough to encourage field
      experiments with sufficiently large number of animals to prove or disprove these
      preliminary findings that lower housing density and permanent breeding cage,
      together or separately, may enhance reproduction particularly in multiparous blue
      fox vixens.

PMID- 17548177
TI  - Effects of black cohosh on estrogen biosynthesis in normal breast tissue in
      vitro.
AB  - OBJECTIVES: To investigate the effect of black cohosh on the estrogen
      biosynthesis in the breast in vitro. METHODS: Steroid sulfatase (STS) activity
      was studied in normal breast tissue obtained from pre- and postmenopausal women
      undergoing reduction mammoplasty. STS protein expression was studied by
      immunohistochemistry and western blotting. Breast tissue was incubated in vitro
      without or with black cohosh (iCR) at concentrations ranging from 0.1mg/ml to 1
      ng/ml. STS activity was evaluated by incubating homogenized breast tissue with
      [3H]-estrone sulfate, separating the formed products, estrone (E1) and estradiol
      (E2), by thin layer chromatography and measuring the amounts of E1 and E2 by
      scintillation counting. RESULTS: STS protein expression and enzymatic activity
      were detected in all specimens investigated. In all groups, significantly more E1
      than E2 was produced. Local estrogen formation was decreased in premenopausal
      breast tissue by treatment with iCR at 0.1mg/ml (p<or=0.05). CONCLUSIONS: iCR
      decreases local estrogen formation in normal human breast tissue in vitro. This
      may contribute to the lack of hormonal effects of black cohosh in breast tissue
      observed in previous studies.

PMID- 17548178
TI  - Correlation between drug dissolution and polymer hydration: a study using texture
      analysis.
AB  - Texture analysis is a new approach in pharmaceutical research and development;
      this study evaluated the correlation between drug dissolution and polymer
      hydration from a modified release matrix tablet of pseudoephedrine hydrochloride
      using a texture analyzer. A series of matrix tablets of pseudoephedrine was
      designed and prepared. Modified drug release was achieved by combined use of
      matrix excipients Polyox WSR301 (PEO) and Compritol 888ATO (GB). Dissolution
      profiles of the tablets were assessed using USP Method II. Polymer swelling
      behaviors during dissolution were measured using a texture analyzer. Increase in
      proportion of PEO and GB in the formulation reduced drug dissolution within the
      first 90 min. However, drug release was complete in 6h due to high aqueous
      solubility of pseudoephedrine. Linear correlations were observed among drug
      dissolution, polymer content and parameters of texture analysis including
      hydrogel thickness and AUC(TA) for formulations that contained hydrophilic PEO.
      The study demonstrated a unique application of a texture analyzer in
      characterization of modified release matrix tablets.

PMID- 17548179
TI  - Studies of the chronological course of wisdom tooth eruption in a Japanese
      population.
AB  - The importance of forensic age estimation in living subjects has grown over the
      last few years. In dental age estimation, tooth eruption is a parameter of
      developmental morphology that can be analyzed by either clinical examination or
      by evaluation of dental X-rays. In the present study, we determined the stage of
      wisdom tooth eruption in 549 male and 751 female Japanese subjects aged 14-26
      years based on radiological evidence from 1300 conventional orthopantomograms.
      The results presented here provide useful data on the age of alveolar, gingival,
      and complete emergence of the third molars in the occlusal plane that can be
      utilized for forensic estimation of the minimum and most probable ages of
      investigated persons.

PMID- 17548180
TI  - Population data from the New South Wales Aboriginal Australian sub-population for
      the profiler plus autosomal short tandem repeat (STR) loci.
AB  - It is a requirement that forensic DNA profiling evidence be accompanied by an
      estimation of its weight, in order that the court can assign an appropriate
      probative value to it during legal proceedings. There are various models by which
      this estimation can be made, but each relies on approximations of the allele
      frequencies in the relevant population. This report provides the results of
      population genetic analyses at nine autosomal short tandem repeat (STR) loci for
      the Aboriginal Australian sub-population of New South Wales, Australia.

PMID- 17548181
TI  - A case report of facial nerve hemangioma.
AB  - Facial nerve hemangioma is a rare benign tumor that originates from the venous
      plexus surrounding the facial nerve. A case of facial nerve hemangioma in the
      geniculate ganglion was reported. A 47-year-old man was referred with a left
      progressive facial palsy over 1 year. There were no complaints of associated
      hearing loss, tinnitus, headache, dizziness or otalgia. He had a left-side grade
      VI (House and Brackmann) facial palsy. Audiometry revealed normal hearing
      thresholds in conversation area bilaterally. CT imaging demonstrated a tumor at
      the left first genu of the facial nerve with expansion to the cochlea wall and
      middle skull base. MRI imaging demonstrated a centrally enhancing lesion
      measuring 5 mm x 10 mm in the geniculate ganglion. The tumor was totally removed
      by the middle cranial fossa approach. At the time of surgery the facial nerve was
      destroyed by the tumor in the geniculate ganglion. Histopathological examination
      diagnosed a hemangioma.

PMID- 17548182
TI  - Life and death in bovine monocytes: the fate of Mycobacterium avium subsp.
      paratuberculosis.
AB  - We previously reported that the number of acid-fast bacilli within Mycobacterium
      paratuberculosis-infected bovine monocytes increased steadily during an 8-day
      incubation period in vitro, despite a decrease in the number of viable bacilli as
      estimated by a radiometric method. In this study, we used differential live/dead
      staining of bacilli from infected monocytes to show that the percentage of viable
      bacilli decreased during an 8-day incubation period. We observed poor phagosome
      lysosome fusion in monocytes that had ingested viable M. paratuberculosis (30%
      phagosome-lysosome fusion), while monocytes that ingested heat killed M.
      paratuberculosis exhibited 94% phagosome-lysosome fusion at 24h after infection.
      Treatment with the selective Ca(2+)/CaM and PI3 kinase inhibitors (i.e. KN62 and
      Wortmannin) in combination increased the survival of M. paratuberculosis in
      bovine monocytes without significantly altering phagosome-lysosome fusion.
      Scanning electron microscopy suggested that M. paratuberculosis-infected
      monocytes were less differentiated (smaller and less spreading) than uninfected
      monocytes at 4 and 8 days of infection. Overall, these data suggest that both
      multiplication and killing of intracellular M. paratuberculosis occur
      concomitantly in bovine monocytes. Monocytes in turn may be adversely affected by
      the bacilli, their products, or factors released from infected monocytes.

PMID- 17548183
TI  - Positive affective style covaries with stimulated IL-6 and IL-10 production in a
      middle-aged community sample.
AB  - An emerging literature indicates that dispositional positive affect (PA) may play
      a protective role in health and render individuals less susceptible to
      inflammatory diseases. In this regard, it has been suggested that PA is
      associated with diminished activation of innate immune pathways. To explore this
      possibility, we examined relationships between trait positive emotional style, as
      assessed by the Positive and Negative Affect Schedule, and monocyte-derived
      lipopolysaccharide-induced production of the pro- and anti-inflammatory
      cytokines, interleukin (IL)-6, IL-1beta, TNF-alpha, and IL-10, among 146 healthy
      adults aged 30-54. After controlling for demographic factors and other covariates
      (age, gender, race, body mass index and white blood cell count), hierarchical
      regression analyses revealed an inverse association between trait PA and
      stimulated production of IL-6 (DeltaR(2)=.03, b=-.18, p <.04) and IL-10
      (DeltaR(2)=.09; b =-.32, p <.01), with the latter association obtained only in
      men. No association was observed between trait PA and stimulated IL-1beta or TNF
      alpha. Additionally, trait negative affect was unrelated to any of the stimulated
      cytokine levels. These initial findings suggest that individuals higher in trait
      positive emotional style show decreased in vitro production of the early
      inflammatory mediators IL-6 and IL-10 in response to stimulation with endotoxin
      which may confer protection against the emergence and progression of inflammatory
      diseases. Further exploration of this potential psychophysiological pathway is
      warranted.

PMID- 17548184
TI  - The significant negative impact of in-hospital venous thromboembolism after
      cardiovascular procedures.
AB  - Our objective was to assess the impact of venous thromboembolism (VTE) on common
      postoperative cardiovascular surgical patients. An administrative database, the
      Nationwide Inpatient Sample (NIS, a sampling of 20% of all inpatients across the
      United States), from 1998 to 2001, was queried for all patients who were
      hospitalized for primary procedural diagnosis of abdominal aortic aneurysm repair
      (AAA), amputation (AMP), coronary artery bypass grafting (CABG), carotid
      endarterectomy (CEA), lower extremity revascularization (LE), and aortic or
      mitral valve repair (VALV) and for secondary diagnosis of VTE, using standard ICD
      9-CM codes. To validate these findings for specificity, the same patient
      procedure groups with a secondary code of VTE and the same hospitalization
      procedural code for inferior vena cava (IVC) filter were also analyzed. Factors
      relating to VTE and the outcomes of death, length of stay (LOS), and unfavorable
      discharge were analyzed by logistical regression, with odds ratios (ORs) reported
      as well as analysis of covariance for cost and LOS determinations. A total of
      191,666 patients were identified from the NIS, with a mean age of 68 years, 65%
      men, 85% white race, and a mean VTE incidence of 0.68%. VTE incidence varied with
      primary procedure: AAA = 1.2%, AMP = 1.1%, CABG = 0.54%, CEA = 0.26%, LE = 0.78%,
      VALV = 0.63%. VTE was more likely with AAA (OR = 3.9), AMP (3.1), LE (2.8), VALV
      (2.0), and CABG (1.9) (all compared with CEA, P < 0.0001) and female gender
      (1.14, P =0.03) but not race or age. Mortality was associated with increased age
      (1.05), female gender (1.2), and VTE (3.4) (all P < 0.0001). Inpatient costs were
      14% higher (P < 0.001), and LOS was increased by 68% compared with those patients
      not having a VTE (P < 0.0001). Unfavorable discharge status was associated with
      increased age (1.05), female gender (1.4), and VTE (2.2), among others. A similar
      magnitude of effect was observed with the subgroup analysis (n = 150) of those
      undergoing the index procedures who received an IVC filter during the same
      hospitalization as VTE diagnosis, including increased risk of death, cost, LOS,
      and unfavorable discharge (all P < 0.001). The occurrence of VTE is not common
      and varies with the cardiovascular procedure but significantly increases the risk
      of in-hospital death, cost, LOS, and unfavorable discharge. Process variables
      should be examined to identify practice patterns that might better prevent this
      complication.

PMID- 17548185
TI  - Embryonic oxidative stress as a mechanism of teratogenesis with special emphasis
      on diabetic embryopathy.
AB  - Reactive oxygen species (ROS) are involved in the etiology of numerous diseases
      including cardio-vascular diseases and diabetes mellitus. There is evidence that
      several teratogens affect the developing embryo by increasing its oxidative
      stress and, because of its relatively weak antioxidant defense, especially at the
      early stages of organogenesis, result in severe embryonic damage. This mechanism
      seems to operate in diabetes-induced embryonic damage as well as in the mechanism
      of teratogenicity caused by ionizing radiation, hypoxia, alcohol and cocaine use
      and cigarette smoking. We studied the role of oxidative stress in diabetic
      induced embryopathy, both in vivo and in vitro. Under diabetic condition there
      was a significant decrease in the activity of endogenous antioxidant enzymes and
      of vitamins C and E in the embryos and their yolk sacs. The lowest activity was
      observed in the malformed experimental embryos when compared to experimental
      embryos without anomalies. Similar results were obtained in the Cohen diabetic
      rats, where the diabetic prone (CDs) rats were unable to increase their
      antioxidant enzyme activity in spite of the diabetes. Studies performed by other
      investigators show similar results. Human and animal studies show that the main
      mechanism of fetal damage induced by high levels of ionizing irradiation, cocaine
      and alcohol abuse, hypoxia and cigarette smoking is also by increased embryonic
      oxidative stress. Similarly, several drugs exert their teratogenic activity via
      embryonic oxidative stress. Abnormal placentation may also cause enhanced
      placental oxidative stress, resulting in embryonic death, preeclampsia or
      congenital anomalies. Inability of the developing embryo to cope with that stress
      may result in embryonic death and/or congenital anomalies. Animal studies also
      show that a variety of antioxidants are effective in decreasing the damaging
      effects of heightened oxidative stress induced by teratogens. Effective
      antioxidants, which might also be of clinical use, include vitamins C and E,
      carotenoids, folic acid, as well as synthetic products. Appropriate clinical
      studies with antioxidants in pregnancies of high risk to develop oxidative stress
      are needed, since non-toxic antioxidants might prove an efficient and inexpensive
      way to reduce the rate of some serious and sometimes fatal congenital anomalies.

PMID- 17548186
TI  - Microencapsulation of extract containing shikonin using gelatin-acacia
      coacervation method: a formaldehyde-free approach.
AB  - The application of microcapsule for pharmaceutical dosage form for various drugs
      has received considerable attention in recent years due to its multiple
      advantages. The most frequently used crosslinking agent formaldehyde in the
      gelatin-acacia microencapsulation process was altered by glycerol in this study.
      The effect of various parameters such as the concentration of surfactant,
      concentration of gelatin and continuous phase pH condition on the microcapsule
      particle size distribution was experimentally investigated. It was shown that the
      optimum concentration for surfactant/oil ratio is 1/10 and gelatin/oil ratio is
      1/5 in the pH condition of approximately 4-6 for the coacervation process.
      Results obtained from microscopy observation revealed that one core microcapsule
      prepared by 6% glycerol was no different from formaldehyde. Hence, glycerol was
      demonstrated to be a good potential non-toxic crosslinking material for the
      applications of encapsulated extract containing shikonin.

PMID- 17548187
TI  - Managing community-acquired pneumonia: a European perspective.
AB  - Community-acquired pneumonia (CAP) is a common disease and a frequent cause of
      morbidity and mortality worldwide. It puts an enormous burden on medical and
      economic resources, particularly if hospitalization is required. Initial
      antibacterial therapy for CAP is usually empirical, as culture and antibacterial
      sensitivity test results are rarely available at initial diagnosis. Any agent
      selected for empirical therapy should have good activity against the pathogens
      commonly associated with CAP, a favorable tolerability profile, and be
      administered in a simple dosage regimen for good compliance. Streptococcus
      pneumoniae remains the most common causative pathogen, although the incidence of
      this organism varies widely. Streptococcus pneumoniae strains with decreased
      susceptibility to penicillin have become increasingly prevalent over the past 30
      years and are now a serious problem worldwide. In addition, an increase in the
      prevalence of pneumococci resistant to macrolides has been observed in Europe
      over recent years. Mycoplasma pneumoniae and Chlamydia pneumoniae are among the
      most common atypical pathogens isolated from patients with CAP. Haemophilus
      influenzae, Staphylococcus aureus and Moraxella catarrhalis are less commonly
      identified as causative organisms. The emergence and spread of resistance to
      commonly used antibiotics has challenged the management of CAP. Multiple sets of
      CAP guidelines have been published to address the continued changes in this
      complex disease.

PMID- 17548188
TI  - Surface plasmon resonance detection of blood coagulation and platelet adhesion
      under venous and arterial shear conditions.
AB  - A surface plasmon resonance (SPR) based flow chamber device was designed for real
      time detection of blood coagulation and platelet adhesion in platelet rich plasma
      (PRP) and whole blood. The system allowed the detection of surface interactions
      throughout the 6mm length of the flow chamber. After deposition of thromboplastin
      onto a section of the sensor surface near the inlet of the flow chamber,
      coagulation was detected downstream of this position corresponding to a SPR
      signal of 7 to 8 mRIU (7 to 8 ng/mm2). A nonmodified control surface induced
      coagulation 3.5 times slower. Platelet adhesion to gold and fibrinogen coated
      surfaces in the magnitude of 1.25 and 1.66 mRIU was also shown with platelets in
      buffer, respectively. SPR responses obtained with PRP and whole blood on surfaces
      that were methylated or coated with von Willebrand factor (vWF), fibrinogen, or
      collagen, coincided well with platelet adhesion as observed with fluorescence
      microscopy in parallel experiments. The present SPR detection equipped flow
      chamber system is a promising tool for studies on coagulation events and blood
      cell adhesion under physiological flow conditions, and allows monitoring of short
      range surface processes in whole blood.

PMID- 17548189
TI  - A nanohybrid membrane with lipid bilayer-like properties utilized as a
      conductimetric saccharin sensor.
AB  - Since their introduction, artificial lipid bilayer membranes were used in a wide
      array of applications, such as sensors, biocompatible materials and study-models
      of the cell's outer boundary. Here, we present a nanohybrid membrane using an
      inorganic host and amphiphilic organic molecules with lipid bilayer-like
      properties. The stability of the presented mimetic membrane is significantly
      improved when compared to existing methods. The nanohybrid membrane exhibited two
      thermotropic phases corresponding to the L(alpha) and L(beta) phases that lipid
      bilayer membranes are known to adopt. Integration of cholesterol molecules into
      the nanohybrid membrane lead to the same qualitative effects as in lipid
      bilayers, including expansion of the bilayer spacing and decrease of the L(alpha)
      to L(beta) transition enthalpy. To further illustrate the similarities of the
      synthesized membrane with a lipid bilayer, the ability of the nanohybrid membrane
      to function as saccharin conductimetric sensor was evaluated. The lower limit of
      detection of the sensor was 6 microM and the linear range of response was from 20
      to 400 microM.

PMID- 17548190
TI  - An EQCM study on the interaction of heparin with the charge-transfer complex
      generated during o-tolidine electrooxidation: a biosensing mode with a
      dynamically renewed surface.
AB  - The electrooxidation of o-tolidine (oTD) was investigated via the electrochemical
      quartz crystal microbalance (EQCM) technique. The formation and breakage of the
      poorly soluble charge-transfer complex (CTC) occurred during the redox switching
      of oTD, and the CTC precipitation on and its removal from the electrode surface
      led to a V-shaped frequency response to the cyclic voltammetric switching of oTD.
      The V-shaped frequency response to the redox switching of the CTC/oTD "couple"
      and the electrode-collection efficiency of the CTC precipitate were notably
      enhanced by the introduction of sodium heparin due to the formation of the CTC
      heparin adduct as reported here for the first time. FTIR and UV-Vis
      characterizations also supported the interaction between the CTC and heparin. The
      molar ratio of the positively charged CTC to negatively charged heparin of the
      adduct was estimated here to be between 31.5 and 36.5, being close to the
      anticipated value, 37.5, for the full electrical neutralization in the adduct. An
      EQCM-based biosensor featured by a dynamically renewed surface of the detection
      electrode was proposed for heparin assay, with a limit of detection of 18.5 nM
      (S/N=3) in pH 6.0 Britton-Robinson buffer solution containing a 10-fold diluted
      blood serum. This method is convenient in operation and highly free from the
      interference from coexisting substances including proteins. The new and
      intriguing biosensing concept based on the labile CTC-"target" adduct is featured
      by a dynamically renewable and regenerable surface of the detection electrode,
      and it is highly recommended for wide biosensing and electroanalytical
      applications.

PMID- 17548191
TI  - Laparoscopy for metastatic colorectal cancer.
AB  - Patients with metastatic disease from colorectal cancer are now living twice as
      long as they were one decade ago. With this increasing life expectancy, we are
      beginning to see these patients strive for an acceptable and improved quality of
      life. Medical advances have led to unanswered questions regarding the role of
      surgery in metastatic colorectal cancer. Despite the increasing application of
      laparoscopy for primary treatment of colorectal cancer, the appropriate role for
      laparoscopy in patients with stage IV disease has yet to be defined. This review
      addresses this topic and suggests treatment algorithms for patients with
      metastatic colorectal cancer. While unresectable, metastatic colorectal cancer
      remains incurable at the current time, continued advances will inevitably
      challenge this presumption and it is crucial to outline the role of laparoscopy
      in this patient population.

PMID- 17548192
TI  - The effects of heat treatment on technological properties in Red-bud maple (Acer
      trautvetteri Medw.) wood.
AB  - Heat treatment is often used to improve the dimensional stability of wood. In
      this study, the effects of heat treatment on technological properties of Red-bud
      maple (Acer trautvetteri Medw.) wood were examined. Samples obtained from Duzce
      Forest Enterprises, Turkey, were subjected to heat treatment at varying
      temperatures (120 degrees C, 150 degrees C and 180 degrees C) and for varying
      durations (2h, 6h and 10h). The technological properties of heat-treated wood
      samples and control samples were tested. Compression strength parallel to grain,
      bending strength, modulus of elasticity in bending, janka-hardness, impact
      bending strength, and tension strength perpendicular to grain were determined.
      The results showed that technological strength values decreased with increasing
      treatment temperature and treatment times. Red-bud maple wood could be utilized
      by using proper heat treatment techniques with minimal losses in strength values
      in areas where working, and stability such as in window frames, are important
      factors.

PMID- 17548193
TI  - Adenosine phosphonate inhibitors of lipid II: alanyl tRNA ligase MurM from
      Streptococcus pneumoniae.
AB  - Adenosine and 2'-deoxyadenosine phosphonate transition state analogues act as the
      first inhibitors for the MurMN/FemABX family of tRNA-dependent ligases implicated
      in high-level penicillin resistance in gram-positive bacteria.

PMID- 17548194
TI  - Synthesis of marine alkaloid: 8,9-dihydrocoscinamide B and its analogues as Novel
      class of antileishmanial agents.
AB  - A series of marine alkaloid 8,9-dihydrocoscinamide B, its analogues and
      indolylglyoxylamide derivatives have been synthesized and screened for their in
      vitro antileishmanial activity profile in promastigote and amastigote models.
      Compounds 7 and 10 have shown 99-100% inhibition against promastigotes and 97-98%
      inhibition against amastigotes at a concentration of 10 microg/ml.

PMID- 17548195
TI  - Orally active antimalarials: synthesis and bioevaluation of a new series of
      steroid-based 1,2,4-trioxanes against multi-drug resistant malaria in mice.
AB  - A new series of steroid-based 1,2,4-trioxanes 7a-f, 8a-f and 9b-e have been
      synthesized and evaluated for their antimalarial activity against multi-drug
      resistant Plasmodium yoelii in Swiss mice by oral route. The biological activity
      shows a strong dependence on the size and the nature of the steroidal side chain.
      Pregnane-based trioxanes 8a-f show better activity profile than trioxanes 7a-f
      and 9b-e, derived from cholesterol and tigogenine, respectively.

PMID- 17548196
TI  - Anti-malarial activity of N6-modified purine analogues.
AB  - Plasmodium falciparum causes one of the deadliest forms of malaria and resistance
      to the currently available drugs makes it imperative to develop new, safe and
      potent drugs. Parasites such as P. falciparum are unable to synthesise purines de
      novo and to this end often have multiple purine uptake and salvage systems. With
      this in mind, we have designed and synthesised libraries of purine analogues as
      potential anti-malarial agents. Herein, we report three compounds with promising
      activity against the highly chloroquine-resistant VS1 P. falciparum namely: N(6)
      hydroxyadenine (1c), 2-amino-N(6)-aminoadenosine (2b) and 2-amino-N(6)-amino-N(6)
      methyladenosine (4b).

PMID- 17548197
TI  - 4-Amino-5-vinyl-3(2H)-pyridazinones and analogues as potent antinociceptive
      agents: Synthesis, SARs, and preliminary studies on the mechanism of action.
AB  - A series of 4-amino-5-vinyl-3(2H)-pyridazinones and analogues were synthesized
      and their antinociceptive effect was evaluated in the mouse abdominal
      constriction model. Several of the novel compounds showed ED(50) values in the
      range 6-20mg/kg/sc and demonstrated to be able to completely protect all the
      treated animals from the effect of the noxious stimulus at 30 mg/kg/sc. SAR
      studies confirmed the essential role played by an amino or substituted amino
      function at position 4 and by a vinyl group at position 5 of the diazine system.

PMID- 17548198
TI  - Synthesis and antiproliferative activity of clausine E, mukonine, and koenoline
      bioisosteres.
AB  - Aza-analogues of clausine E, mukonine and koenoline were prepared from 1
      (benzenesulfonyl)-1H-pyrrolo[2,3-b]pyridine-3-carboxaldehyde and their
      antiproliferative activity was evaluated against miscellaneous cancer cell lines
      and compared to those obtained with clausine E and mukonine.

PMID- 17548199
TI  - Changes in cell morphology affect the quantification of intercellular
      communication.
AB  - The scrape loading and dye transfer (SL/DT) method is a functional assay widely
      used to evaluate the level of the intercellular communication via gap junction.
      Initially, the evaluation of the degree of communication was done by counting the
      rows of fluorescent cells from the scrape. Its substitution by fluorescence
      distance or area, determinated by morphometric softwares, was proposed as the
      best way of communication measurement. Considering that normal cells change their
      morphology during different phases of growth in monolayer cultures we proposed to
      evaluate the possible influence of the cell morphology changes on the
      quantification of intercellular communication when the SL/DT method is used. The
      present data indicates that GJIC capacity should be rather quantified by counting
      the fluorescent cell rows than by the measurement of the fluorescence distance or
      area, when the goal is to evaluate the cell communication along different phases
      of cell culture. Normal cells growing in monolayer culture decrease their
      diameter according to their final density of saturation, impairing the
      quantification of GJIC capacity by morphometric analysis.

PMID- 17548201
TI  - Preoperative risk stratification in infective endocarditis. Does the EuroSCORE
      model work? Preliminary results.
AB  - OBJECTIVE: There is an important role for risk prediction in cardiac surgery.
      Prediction models are useful in decision making and quality assurance. Patients
      with infective endocarditis (IE) have a particularly high risk of mortality. The
      aim was to assess the performance of European System for Cardiac Operative Risk
      Evaluation (EuroSCORE) in IE. METHODS: The additive and logistic EuroSCORE models
      were applied to all patients undergoing surgery for IE (Duke criteria) between
      January 1995 and April 2006 within our prospective institutional database.
      Observed and predicted mortalities were compared. Model calibration was assessed
      with the Hosmer-Lemeshow test. Model discrimination was tested by determining the
      area under the receiver operating characteristic (ROC) curve. RESULTS: One
      hundred and eighty-one consecutive patients undergoing 191 operations were
      analyzed. Observed mortality was 28.8%. For the entire cohort the mean additive
      score was 10.4 (additive predicted mortality of 14.2%). The mean logistic
      predicted mortality was 27.1%. Discriminative power was good for the additive and
      the logistic models for the entire series. Area under ROC curve were 0.83
      (additive) and 0.84 (logistic) for the entire cohort, 0.81 and 0.81 for the
      aortic position, 0.91 and 0.92 for the mitral position, 0.81 and 0.81 for the
      native valve, 0.82 and 0.83 for the prosthetic valves, and 0.81 and 0.51 for the
      gram-positive microorganisms, respectively. CONCLUSIONS: This initial sample may
      be small; however, additive and logistic EuroSCORE adequately stratify risk in
      IE. Logistic EuroSCORE has been calibrated in IE, a special group of very high
      risk patients. Further studies with larger sample sizes are required to confirm
      these initial results.

PMID- 17548202
TI  - Lutein, zeaxanthin and astaxanthin protect against DNA damage in SK-N-SH human
      neuroblastoma cells induced by reactive nitrogen species.
AB  - The purpose of this study was to evaluate the ability of the predominant
      carotenoids (lutein and zeaxanthin) of the macular pigment of the human retina,
      to protect SK-N-SH human neuroblastoma cells against DNA damage induced by
      different RNOS donors. Although astaxanthin has never been isolated from the
      human eye, it was included in this study because its structure is very close to
      that of lutein and zeaxanthin and because it affords protection from UV-light.
      DNA damage was induced by GSNO-MEE, a nitric oxide donor, by Na(2)N(2)O(3), a
      nitroxyl anion donor and by SIN-1, a peroxynitrite-generating agent. DNA damage
      was assessed using the comet assay, a rapid and sensitive single cell gel
      electrophoresis technique able to detect primary DNA damage in individual cells.
      The tail moment parameter was used as an index of DNA damage. The values of tail
      moment increased in all the samples incubated with the RNOS donors, indicating
      DNA impairment. Data obtained show that the ability of zeaxanthin, lutein, and
      astaxanthin to reduce the DNA damage depends on the type of RNOS donor and the
      carotenoid concentration used. All the carotenoids studied were capable of
      protecting against DNA damage in neuroblastoma cells when the cells were exposed
      to GSNO-MEE. However, a different behaviour was present when the other two RNOS
      donors were used. The presence of a carotenoid alone (without an RNOS donor) did
      not cause DNA damage. Spectrophotometric studies showed that the order with which
      tested carotenoids reacted with RNOS was not always in agreement with the DNA
      protection results. The data from this study provides additional information on
      the activities of the macular pigment carotenoids of the human retina.

PMID- 17548203
TI  - Cilostazol reduces inflammatory burden and oxidative stress in hypertensive type
      2 diabetes mellitus patients.
AB  - OBJECTIVES: Inflammation and oxidative stress cause genesis and progression of
      atherosclerosis in diabetes. This study aimed to assess effects of Cilostazol on
      these factors in hypertensive type 2 diabetic patients. MATERIALS AND METHODS: In
      randomized, open, add-on preventive controlled clinical trial design, 60
      hypertensive type 2 diabetics aged >or=45 years were evaluated clinically and for
      total leukocyte count, erythrocyte sedimentation rate, serum albumin, serum hsC
      reactive protein, plasma malondialdehyde, blood reduced glutathione and HbA1c
      levels. After informed consent, 30 patients received Cilostazol (100mg) twice
      daily orally as add-on therapy. At 1 month follow-up, 26 patients in control
      group and 22 patients in Cilostazol group completed the trial and particular
      parameters were re-evaluated. RESULTS: The mean age and duration of diabetes were
      55+/-7 years and 8+/-6 years, respectively. At follow-up, the Cilostazol group
      showed significant (p<0.001) decrease in hsC-reactive protein (23.6%),
      erythrocyte sedimentation rate (38.7%), total leukocyte count (12.6%), plasma
      malondialdehyde (17.6%), HbA1c (0.17%, p=0.002) and increase in serum albumin
      (11.9%), blood reduced glutathione (3.5%) from baseline. UKPDS 10 years risk of
      coronary heart disease decreased by 6% (p=0.002). The control group did not show
      significant improvement in inflammatory profile, oxidative status and HbA1c.
      CONCLUSION: Inflammatory and oxidative stress is high in hypertensive type 2
      diabetic patients. Cilostazol reduces these factors as well as coronary heart
      disease risk in diabetes mellitus.

PMID- 17548204
TI  - Prolonged treatment with aminoguanidine strongly inhibits adipocyte semicarbazide
      sensitive amine oxidase and slightly reduces fat deposition in obese Zucker rats.
AB  - Beneficial effects of aminoguanidine (AG) on diabetic vascular complications
      result from prevention of protein glycation, inhibition of inductible NO
      synthase, and inhibition of vascular semicarbazide-sensitive amine oxidase
      (SSAO). However, influence of AG on adipose tissue deposition has been poorly
      investigated in obesity. Considering that SSAO is highly expressed in fat cells,
      and that a SSAO blocker has been recently reported to reduce body weight gain in
      obese mice, this work aimed to investigate the influence of AG on adipose tissue
      functions. First, AG was shown to directly inhibit SSAO activity in cultured
      adipocytes. Although AG did not directly alter lipolytic activity in human
      adipocytes, it inhibited benzylamine-induced antilipolysis via SSAO (but not NO
      synthase) inhibition. When AG was i.p. administered to obese Zucker rats (270
      micromol kg(-1)day(-1) for 3 weeks), treated rats lost their capacity to oxidize
      benzylamine in a SSAO-dependent manner in adipose tissues and in cerebral
      vessels. Monoamine oxidase activity was unmodified in liver, skeletal muscles or
      adipose tissues and tended to increase in brain vessels. AG-treatment did not
      change body weight gain or hyperinsulinemic state of obese rats but slightly
      reduced subcutaneous fat deposition. AG did not modify insulin responsiveness in
      adipocytes but impaired the effects of SSAO substrates, such as glucose transport
      activation and lipolysis inhibition by methylamine or benzylamine plus vanadate.
      These results show that complete impairment of SSAO activity produced by AG
      treatment in obese rats was likely responsible for a weak limitation of fat
      deposition. Previously proposed for prophylaxis in diabetes, AG may be useful for
      treating obesity via its SSAO blocking properties.

PMID- 17548205
TI  - Classical PKC isoforms in cancer.
AB  - Protein kinases C (PKCs) are a family of serine/threonine kinases which are
      involved in tumor formation and progression. Although PKC over-expression has
      been shown to contribute to cell transformation, PKCs are not considered to be
      classical oncogenes which are activated by mutations, but considered as tumor
      promoters that enhance multiple cellular signaling pathways. Over the last two
      decades a lot of evidence has emerged demonstrating a role for various PKC
      isoforms in cancer. Small molecular weight inhibitors and antisense molecules
      have been developed, specifically targeting the calcium dependent classical
      isoforms of PKC. This review focuses on the role of classical PKCs in cancer and
      the results obtained by attempting to inhibit these enzymes to achieve a
      therapeutic benefit.

PMID- 17548206
TI  - Proteomic technologies in the study of kinases: novel tools for the investigation
      of PKC in the heart.
AB  - Recent developments in the field of protein separation allows for the analysis of
      qualitative and quantitative global protein changes in a particular state of a
      biological system. Due to the enormous number of proteins potentially present in
      a cell, sub-fractionation and the enrichment of specific organelles are emerging
      as a necessary step to allow a more comprehensive representation of the protein
      content. The proteomic studies demonstrate that a key to understand the
      mechanisms underlying physiological or pathological phenotypes lies, at least in
      part, in post-translational modifications (PTMs), including phosphorylation of
      proteins. Rapid improvements in proteomic characterization of amino acid
      modifications are further expanding our comprehension of the importance of these
      mechanisms. The present review will provide an overview of technologies available
      for the study of a proteome, including tools to assess changes in protein
      quantity (abundance) as well as in quality (PTM forms). Examples of the recent
      application of these technologies and strategies in the field of kinase
      signalling will be provided with particular attention on the role of PKC in the
      heart. Studies of PKC-mediated phosphorylation of cytoskeletal, myofilament and
      mitochondrial proteins in the heart have provided great insight into the
      phenotypes of heart failure, hypertrophy and cardioprotection. Proteomics studies
      of the mitochondria have provided novel evidences for kinase signalling cascades
      localized to the mitochondria, some of which are known to involve various
      isoforms of PKC. Proteomics technologies allow for the identification of the
      different PTM forms of specific proteins and this information is likely to
      provide insight into the determinants of morphological as well as metabolic mal
      adaptations, both in the heart and other tissues.

PMID- 17548208
TI  - The role of adenosine A1 and A2A receptors of entorhinal cortex on piriform
      cortex kindled seizures in rats.
AB  - In this research the role of adenosine A1 and A2A receptors of the entorhinal
      cortex on piriform cortex kindled seizures was investigated. In piriform cortex
      kindled rats, N6-cyclohexyladenosine (CHA), a selective A1 receptor agonist, 1,3
      dimethyl-8 cyclopenthylxanthine (CPT), a selective A1 receptor antagonist,
      CGS21680 hydrochloride (CGS), a selective A2A receptor agonist and ZM241385 (ZM),
      a selective A2A receptor antagonist were injected into the entorhinal cortex
      bilaterally. Five minutes later, animals were stimulated and seizure parameters
      were recorded. CHA (10 and 100microM) decreased the afterdischarge duration
      (ADD), stage 5 seizure duration (S5D), and seizure duration (SD), and increased
      the latency to stage 4 of the seizure (S4L) significantly. Bilateral
      microinjection of CPT (100microM) increased ADD, S(5)D, and SD, and reduced S(4)L
      significantly. Pretreatment of animals with CPT (50microM) before CHA
      (100microM), reduced the effect of CHA on seizure parameters. On the other hand,
      CGS (1mM) increased only ADD. Bilateral microinjection of ZM had no effect on
      seizure parameters. However, pretreatment of animals with ZM (200microM) before
      CGS (1mM), eliminated the excitatory effect of CGS on seizure parameters. These
      results suggest that activation of A1 receptors of the entorhinal cortex has an
      anticonvulsant, but activation of A2A receptors of this region has a
      proconvulsive effect on piriform cortex kindled seizures.

PMID- 17548207
TI  - Protein kinase C in pain: involvement of multiple isoforms.
AB  - Pain is the primary reason that people seek medical care. At present, chronic
      unremitting pain is the third greatest health problem after heart disease and
      cancer. Chronic pain is an economic burden in lost wages, lost productivity,
      medical expenses, legal fees and compensation. Chronic pain is defined as a pain
      of greater than 2 months duration. It can be of inflammatory or neuropathic
      origin that can arise following nerve injury or in the absence of any apparent
      injury. Chronic pain is characterized by an altered pain perception that includes
      allodynia (a response to a normally non-noxious stimuli) and hyperalgesia (an
      exaggerated response to a normally noxious stimuli). This type of pain is often
      insensitive to the traditional analgesics or surgical intervention. The study of
      the cellular and molecular mechanisms that contribute to chronic pain are of the
      up-most importance for the development of a new generation of analgesic agents.
      Protein kinase C isozymes are under investigation as potential therapeutics for
      the treatment of chronic pain conditions. The anatomical localization of protein
      kinase C isozymes in both peripheral and central nervous system sites that
      process pain have made them the topic of basic science research for close to two
      decades. This review will outline the research to date on the involvement of
      protein kinase C in pain and analgesia. In addition, this review will try to
      synthesize these works to begin to develop a comprehensive mechanistic
      understanding of how protein kinase C may function as a master regulator of the
      peripheral and central sensitization that underlies many chronic pain conditions.

PMID- 17548209
TI  - Angiotensin-(1-7) blocks the angiotensin II-stimulated superoxide production.
AB  - Angiotensin (Ang)-(1-7), a bioactive compound of the renin-angiotensin system,
      exerts effects leading to blood pressure reduction which counterbalance Ang II
      pressor actions. The present study was conducted to examine Ang-(1-7) and Ang II
      effects on superoxide anion production in rat aorta using the lucigenin
      chemiluminescence method. Ang II dose-dependently increased superoxide anion
      formation when compared to control levels; a maximal increase (2.5-fold) was
      observed with 1 x 10(-10)M peptide concentration. The Ang II-stimulated
      superoxide formation was blocked by 1 x 10(-10)M losartan, the specific AT(1)
      receptor antagonist, but not by 1 x 10(-10)M PD 123319, the AT(2) receptor
      antagonist, suggesting that the increased superoxide levels caused by Ang II are
      mediated through AT(1) receptors activation. The Ang II-stimulated superoxide
      production was not modified by 2 x 10(-8)M allopurinol or 1 x 10(-7)M
      indomethacin, but was completely abolished by NAD(P)H oxidase inhibitors: 1 x 10(
      8)M diphenylene iodonium, or 2 x 10(-8)M apocynin, demonstrating that NAD(P)H
      oxidase participates in such response. In contrast to Ang II, Ang-(1-7)
      concentrations ranging 1 x 10(-12) to 1 x 10(-6)M did not modify superoxide anion
      levels, but prevented the Ang II-enhanced superoxide production. In conclusion,
      we demonstrated that Ang-(1-7) blocks the pro-oxidant effects of Ang II, thus
      reducing the superoxide anion production and delaying the hypertension
      development.

PMID- 17548211
TI  - The laterality effect: myth or truth?
AB  - Tzelgov and colleagues [Tzelgov, J., Meyer, J., and Henik, A. (1992). Automatic
      and intentional processing of numerical information. Journal of Experimental
      Psychology: Learning, Memory and Cognition, 18, 166-179.], offered the existence
      of the laterality effect as a post-hoc explanation for their results. According
      to this effect, numbers are classified automatically as small/large versus a
      standard point under autonomous processing of numerical information. However, the
      genuinity of the laterality effect was never examined, or was confounded with the
      numerical distance effect. In the current study, I controlled the numerical
      distance effect and observed that the laterality effect does exist, and affects
      the processing of automatic numerical information. The current results suggest
      that the laterality effect should be taken into account when using paradigms that
      require automatic numerical processing such as Stroop-like or priming tasks.

PMID- 17548210
TI  - A role for "self" in T-cell activation.
AB  - The mechanisms by which alphabeta T-cells are selected in the thymus and then
      recognize peptide MHC (pMHC) complexes in the periphery remain an enigma. Recent
      work particularly with respect to quantification of T-cell sensitivity and the
      role of self-ligands in T-cell activation has provided some important clues to
      the details of how TCR signaling might be initiated. Here, we highlight recent
      experimental data that provides insights into the initiation of T-cell activation
      and also discuss the main controversies and uncertainties in this area.

PMID- 17548212
TI  - Phylogenetics of the brachyuran crabs (Crustacea: Decapoda): the status of
      Podotremata based on small subunit nuclear ribosomal RNA.
AB  - The true crabs, the Brachyura, are generally divided into two major groups:
      Eubrachyura or 'advanced' crabs, and Podotremata or 'primitive' crabs. The status
      of Podotremata is one of the most controversial issues in brachyuran systematics.
      The podotreme crabs, best recognised by the possession of gonopores on the coxae
      of the pereopods, have variously been regarded as mono-, para- or polyphyletic,
      or even as non-brachyuran. For the first time, the phylogenetic positions of the
      podotreme crabs were studied by cladistic analysis of small subunit nuclear
      ribosomal RNA sequences. Eight of 10 podotreme families were represented along
      with representatives of 17 eubrachyuran families. Under both maximum parsimony
      and Bayesian Inference, Podotremata was found to be significantly paraphyletic,
      comprising three major clades: Dromiacea, Raninoida, and Cyclodorippoida. The
      most 'basal' is Dromiacea, followed by Raninoida and Cylodorippoida. Notably,
      Cyclodorippoida was identified as the sister group of the Eubrachyura. Previous
      hypotheses that the dromiid crab, Hypoconcha, is an anomuran were unsupported,
      though Dromiidae as presently composed could be paraphyletic. Topologies
      constrained for podotreme monophyly were found to be significantly worse (P <
      0.04) than unconstrained topologies under Templeton and S-H tests. The clear
      pattern of podotreme paraphyly and robustness of topologies recovered indicates
      that Podotremata as a formal concept is untenable. Relationships among the
      eubrachyurans were generally equivocal, though results indicate the majoids or
      dorippoids were the least derived of the Eubrachyura. A new high level
      classification of the Brachyura is proposed.

PMID- 17548213
TI  - Phylogenetic relationships and morphometric affinities of the Arunachal macaque
      Macaca munzala, a newly described primate from Arunachal Pradesh, northeastern
      India.
AB  - A new species of primate, the Arunachal macaque Macaca munzala, belonging to the
      sinica species-group of the genus, was described from northeastern India in 2005,
      and, based on its appearance and distribution, hypothesised to be closely related
      to M. assamensis and M. thibetana. We subsequently obtained an entire adult male
      specimen and tissue remains from two other M. munzala individuals. Molecular
      analyses establish the distinct identity of the species and indicate a time of
      origin of c. 0.48 mya for it. The species also shows close phylogenetic
      affinities with the allopatric M. radiata and with the geographically closer M.
      assamensis and M. thibetana, possibly mediated by male introgression from an
      ancestral M. assamensis-M. thibetana stock into an ancestral M. munzala stock.
      Morphometric analyses, on the other hand, reiterate its close similarity only
      with M. assamensis and M. thibetana, presumably resulting from convergent
      evolution under similar ecological conditions and along a latitudinal gradient,
      as predicted by Bergmann's and Allen's rules.

PMID- 17548214
TI  - A molecular and histological characterization of cartilage from patients with
      Morquio syndrome.
AB  - OBJECTIVE: To investigate the gene expression profile and the histological
      aspects of articular cartilage of patients affected by Morquio syndrome, a
      lysosomal storage disease characterized by the accumulation of glycosaminoglycans
      within the cells which result in abnormal formation and growth of the skeletal
      system. METHOD: Articular cartilage samples were obtained from the femoral
      condyle of two siblings with Morquio syndrome during surgery performed to treat
      valgus knee. As controls, four biopsy samples of healthy cartilage were obtained
      from four different male multiorgan donors. A Real-Time Polymerase Chain reaction
      (RT-PCR) analysis was performed to evaluate the expression of type I and II
      collagens and aggrecan mRNAs. Histological and immunohistochemical analyses for
      some matrix proteins were carried out on paraffin embedded sections. RESULTS:
      Type I collagen mRNA mean level was higher in the samples of patients with
      Morquio syndrome compared to controls. Type II collagen and aggrecan mRNAs' mean
      expression was instead lower. The morphological appearance of the cartilage
      showed a poorly organized tissue structure with not homogeneously distributed
      cells that were larger compared to normal chondrocytes due to the presence inside
      the vacuoles of proteoglycans which were not metabolized. Chondrocytes were
      negative for collagen II immunostaining while the extracellular matrix was weakly
      positive. Collagen type I immunostaining was positive at cellular level. Keratan
      sulfate showed diffuse positivity and chondroitin-6-sulfate was present
      throughout the cartilaginous thickness. CONCLUSION: In cartilage of patients with
      Morquio syndrome, a low expression of collagen type II and a high expression of
      collagen type I both at protein and molecular levels are evidentiated. This
      finding could give evidence of the reduction in ankle and knee joint movement
      observable in these patients.

PMID- 17548215
TI  - Membrane type-1 matrix metalloproteinase is induced following cyclic compression
      of in vitro grown bovine chondrocytes.
AB  - OBJECTIVE: To determine if membrane type-1 matrix metalloproteinase (MT1-MMP)
      will respond to cyclic compression of chondrocytes grown in vitro and the
      regulatory mechanisms underlying this response. METHODS: Cyclic compression
      (30min, 1kPa, 1Hz) was applied to bovine chondrocytes (6-9-month-old animals)
      grown on top of a biodegradable substrate within 3 days of initiating culture.
      Luciferase assays using bovine articular chondrocytes were undertaken to
      demonstrate the mechanosensitivity of MT1-MMP. Semi-quantitative reverse
      transcription polymerase chain reaction (RT-PCR) and western blot analysis were
      used to establish the time course of gene and protein upregulation in response to
      cyclic compression. The regulation of MT1-MMP was assessed by electrophoretic
      mobility shift assays, RT-PCR and western blot analysis. As well, an MT1-MMP
      decoy oligonucleotide and an extracellular signal-regulated kinase 1/2 (ERK1/2)
      pharmacological inhibitor were utilized to further characterize MT1-MMP
      regulation. RESULTS: After cyclic compression, MT1-MMP showed a rapid and
      transient increase in gene expression. Elevated protein levels were detected
      within 2h of stimulation which returned to baseline by 6h. During cyclic
      compression, phosphorylation of the mitogen activated protein kinase ERK1/2
      increased significantly. This was followed by increased gene and protein
      expression of the transcription factor; early growth factor-1 (Egr-1) and Egr-1
      binding to the MT1-MMP promoter. Blocking Egr-1 DNA binding with a decoy MT1-MMP
      oligonucleotide, downregulated MT1-MMP gene expression. The ERK1/2 inhibitor
      U0126 also reduced Egr-1 DNA binding activity to MT1-MMP promoter sequences and
      subsequent transcription of MT1-MMP. CONCLUSIONS: These data suggest that cyclic
      compression of chondrocytes in vitro upregulates MT1-MMP via ERK1/2 dependent
      activation of Egr-1 binding. Delineation of the regulatory pathways activated by
      mechanical stimulation will further our understating of the mechanisms
      influencing tissue remodeling.

PMID- 17548216
TI  - Differential roles of hippocampal metabotropic glutamate receptors 1 and 5 in
      inhibitory avoidance learning.
AB  - Group I metabotropic glutamate receptors (mGlu1 and 5) have been implicated in
      synaptic plasticity and learning and memory. However, much of our understanding
      of how these receptors in different brain regions contribute to distinct memory
      stages in different learning tasks remains incomplete. The present study
      investigated the effects of the mGlu5 receptor antagonist, 2-methyl-6
      (phenylethynyl)-pyridine (MPEP), and mGlu1 receptor antagonist, (S)-(+)-alpha
      amino-4-carboxy-2-methylbenzene-acetic acid (LY 367385) in the dorsal hippocampus
      on the consolidation and extinction of memory for inhibitory avoidance learning.
      Male, Sprague-Dawley rats were trained in a single-trial step-down inhibitory
      avoidance task. MPEP, LY 367385 or saline were infused bilaterally into the CA1
      region immediately after training or immediately after the first retention test
      which was given 24h after training. Rats receiving MPEP (1.5 or 5.0 microg/side)
      or LY 367385 (0.7 or 2.0 microg/side) infusion exhibited a dose-dependent
      decrease in retention when tested 24h later. MPEP was ineffective while LY 367385
      significantly attenuated extinction when injected after the first retention test
      using an extinction procedure. These findings indicate a selective participation
      of hippocampal group I mGlu receptors in memory processing in this task.

PMID- 17548217
TI  - Functional characterization of the penicillin biosynthetic gene cluster of
      Penicillium chrysogenum Wisconsin54-1255.
AB  - Industrial strain improvement via classical mutagenesis is a black box approach.
      In an attempt to learn from and understand the mutations introduced, we cloned
      and characterized the amplified region of industrial penicillin production
      strains. Upon amplification of this region Penicillium chrysogenum is capable of
      producing an increased amount of antibiotics, as was previously reported
      [Barredo, J.L., Diez, B., Alvarez, E., Martin, J.F., 1989a. Large amplification
      of a 35-kb DNA fragment carrying two penicillin biosynthetic genes in high
      yielding strains of Penicillium chrysogenum. Curr. Genet. 16, 453-459; Newbert,
      R.W., Barton, B., Greaves, P., Harper, J., Turner, G., 1997. Analysis of a
      commercially improved Penicillium chrysogenum strain series, involvement of
      recombinogenic regions in amplification and deletion of the penicillin gene
      cluster. J. Ind. Microbiol. 19, 18-27]. Bioinformatic analysis of the central
      56.9kb, present as six direct repeats in the strains analyzed in this study,
      predicted 15 Open Reading Frames (ORFs). Besides the three penicillin
      biosynthetic genes (pcbAB, pcbC and penDE) only one ORF has an orthologue of
      known function in the database: the Saccharomyces cerevisiae gene ERG25.
      Surprisingly, many genes known to encode direct or indirect steps beta-lactam
      biosynthesis like phenyl acetic acid CoA ligase and transporters are not present.
      Detailed analyses reveal a detectable transcript for most of the predicted ORFs
      under the conditions tested. We have studied the role of these in relation to
      penicillin production and amplification of the biosynthetic gene cluster. In
      contrast to what was expected, the genes encoding the three penicillin
      biosynthetic enzymes alone are sufficient to restore full beta-lactam synthesis
      in a mutant lacking the complete region. Therefore, the role of the other 12 ORFs
      in this region seems irrelevant for penicillin biosynthesis.

PMID- 17548218
TI  - Nitric oxide (NO) serves as a retrograde messenger to activate neuronal NO
      synthase in the spinal cord via NMDA receptors.
AB  - We have recently demonstrated that nitric oxide (NO) produced by neuronal NO
      synthase (nNOS) in the spinal cord is involved in the maintenance of neuropathic
      pain. To clarify whether NO itself affected nNOS activity in the spinal cord as a
      retrograde messenger, we examined the involvement of the NO/cGMP signaling
      pathway in the regulation of nNOS activity by NADPH-diaphorase histochemistry. NO
      generating agents NOR3 (t(1/2)=30min) and SNAP (t(1/2)=5h), but not NOR1
      (t(1/2)=1.8min), significantly enhanced NADPH-diaphorase staining in the spinal
      cord. 8-Br-cGMP also enhanced it similar to that by NOR3, and 8-Br-cAMP and
      forskolin, an activator of adenylate cyclase, enhanced it moderately. NOR1 and
      NOR3 markedly increased the cGMP level in the spinal cord. The enhancement of
      NADPH-diaphorase staining by NOR3 was significantly inhibited by CPTIO, an NO
      scavenger, ODQ, a soluble guanylate cyclase inhibitor, and KT5823, an inhibitor
      of cGMP-dependent protein kinase. Additionally, the NOR3-enhanced nNOS activity
      was completely inhibited by NMDA antagonists MK-801 and d-AP5, partially by the
      GluRepsilon2-selective antagonist CP-101,606, and was attenuated in GluRepsilon1(
      /-) and GluRepsilon1(-/-)/epsilon4(-/-) mice. These results suggest that NO may
      regulate nNOS activity as a retrograde messenger in the spinal cord via
      activation of NMDA receptor containing GluRepsilon1 and GluRepsilon2 subunits.

PMID- 17548219
TI  - The effects on maternal and fetal cardiovascular and acid-base variables after
      the administration of etomidate in the pregnant ewe.
AB  - Etomidate is an intravenous (IV) hypnotic agent characterised by its
      cardiovascular stability. Although etomidate has been satisfactorily used in
      veterinary and human obstetrics, little is known about its effects on the fetus.
      This study determined the cardiovascular and acid-base effects of etomidate
      administration in the pregnant ewe and her fetus. The effects of etomidate were
      evaluated in two separate studies. In the first study, etomidate was administered
      as a 1mg/kg IV bolus; in the second, the drug was administered as a continuous
      infusion of 100 microg/kg/min for 1h, preceded by a 1mg/kg IV bolus. Etomidate
      administration did not depress cardiovascular function in the pregnant ewe or
      fetus. When administered as a continuous infusion, maternal heart rate and blood
      pressure increased during the second half of the infusion and the initial stages
      of recovery. Acid-base alterations led to transient but slight respiratory
      depression in both mother and fetus, probably reflecting the combined effects of
      etomidate on respiration and the positioning of the animal.

PMID- 17548220
TI  - Prevalence of Helicobacter pylori vacA, cagA, cagE, iceA and babA2 genotypes in
      Thai dyspeptic patients.
AB  - OBJECTIVES: To investigate the prevalence of the vacA, cagA, cagE, iceA, and
      babA2 genotypes in Helicobacter pylori strains isolated from Thai dyspeptic
      patients, and to determine whether any correlation exists between these genotypes
      and clinical manifestations. METHODS: Helicobacter pylori was examined in 112
      patients (62 with non-ulcer dyspepsia (gastritis), 34 with peptic ulcer disease,
      and 16 with gastric cancer (GCA)), detected by culture or direct detection from
      gastric biopsies. Allelic variants of the vacA, cagA, cagE, iceA, and babA2
      genotypes were identified by using the polymerase chain reaction. RESULTS: The
      positive rates for the vacAs1, vacAs2, cagA, cagE, iceA1, iceA2, and babA2 genes
      in H. pylori of dyspeptic patients were 100%, 0%, 98.2%, 88.4%, 45.5%, 33.1%, and
      92%, respectively. The allelic variant vacAs1m1 was more prevalent (58%) than
      vacAs1m2 (42%). The cagA and cagE genes were commonly found together (87.5%). The
      most predominant genotypes were vacAs1m1, cagA, cagE, iceA1, and babA2. The
      various genes alone or in combination had no statistically significant
      association with the clinical outcomes (p>0.05). CONCLUSION: Neither single gene
      nor combination of vacA, cagA, cagE, iceA, and babA2 genes was significantly
      helpful in predicting the clinical outcome of H. pylori infection in Thai
      patients. The high prevalence of these genes in H. pylori isolated from Thai
      patient groups suggests that H. pylori strains are geographically dependent.

PMID- 17548221
TI  - Bovine parainfluenza virus type 3 accessory proteins that suppress beta
      interferon production.
AB  - The paramyxovirus P gene encodes accessory proteins antagonistic to interferon
      (IFN). Viral proteins responsible for the IFN antagonism, however, are distinct
      among paramyxoviruses. Here we determine bovine parainfluenza virus type 3
      (bPIV3) IFN antagonists that suppress IFN-beta production, and investigate the
      underlying molecular mechanism. Of bPIV3 P gene products, C and V proteins were
      found to suppress double-stranded RNA-stimulated IFN-beta production. The V
      protein of bPIV3 and Sendai virus in the same genus Respirovirus significantly
      inhibits double-stranded RNA-stimulated IFN-beta production and the IFN-beta
      promoter activation enhanced by overexpression of MDA5 but not RIG-I, and yet
      does not suppress IFN-beta production induced by TRIF, TBK1, and IKKi. The V
      protein of both viruses specifically binds to MDA5 but not RIG-I. These results
      suggest that the V protein targets MDA5 for blockage of the IFN-beta gene
      activation signal. On the other hand, both bPIV3 and Sendai virus C proteins
      modestly inhibited IFN-beta production irrespective of a species of the signaling
      molecules used as an inducer. Interestingly, reporter gene expression driven by
      various promoters was also suppressed by the C proteins irrespective of the
      promoter species. These results demonstrate that the target of the respirovirus C
      protein is undoubtedly different from that of the V protein.

PMID- 17548222
TI  - Immunologically relevant strain polymorphism in the Amastigote Surface Protein 2
      of Trypanosoma cruzi.
AB  - Several evidences suggest that the Amastigote Surface Protein-2 (ASP-2) of
      Trypanosoma cruzi is an important target for immunity during infection. Based on
      this, we considered it important to evaluate its strain polymorphism. Initially,
      we observed the presence of conserved cross-reactive epitopes in amastigotes of
      all parasite strains tested. In addition, the predicted amino acid sequences of
      the genes isolated from the cDNA of amastigotes of CL-Brener, Tulahuen, Colombian
      and G strains displayed a high degree of identity (>80%) to the previously
      described genes of ASP-2. Unexpectedly, Sylvio X10/4 and G strains expressed a
      new isoform of ASP-2 with limited identity to the previously described genes, but
      with a high degree of identity when compared to each other. Immunological studies
      confirmed the presence of cross-reactive epitopes between recombinant proteins
      representing the different isoforms of ASP-2. However, the genetic vaccination of
      mice with the new isoform of asp-2 gene expressed by the G strain failed to
      provide the same degree of protective immunity to a challenge by parasites of the
      Y strain as did asp-2 genes of Y or CL-Brener strains. In summary, we found that
      few strains can express different isoforms of ASP-2 which may not share cross
      protective epitopes.

PMID- 17548223
TI  - Isolation and identification of an scFv antibody against nucleocapsid protein of
      SARS-CoV.
AB  - To develop reagents for early diagnosis and therapeutic drugs against SARS
      associated coronavirus (SARS-CoV), a large (3 x 10(9)) immunized human antibody
      library was constructed from peripheral blood mononuclear cells from six SARS
      convalescent patients. A single chain variable fragment antibody (N18) with high
      affinity against N protein of SARS-CoV was isolated. Sequence analysis revealed
      that the VL gene was composed of VL3h (V lambda subgroup) and JL2 regions and the
      VH gene was composed of VH1-69 (VH1 subgroup), D2-15, D3-22 and JH6 regions.
      Soluble N18 antibody was expressed in Escherichia coli HB2151, purified by Ni-NTA
      affinity chromatography and verified by SDS-PAGE and Western blot. The potential
      application for early diagnosis was evaluated using N protein capture ELISA in
      which N18 antibody demonstrated high sensitive activity in detecting N protein of
      SARS-CoV. Finally, the potential usefulness of the N18 antibody in prophylaxis,
      vaccine design and therapy of SARS is discussed.

PMID- 17548224
TI  - Lipoprotein e (P4) of Haemophilus influenzae: role in heme utilization and
      pathogenesis.
AB  - Lipoprotein e (P4) of Haemophilus influenzae is a phosphomonoesterase, encoded by
      the hel gene, that has been implicated in the acquisition of heme by this
      fastidious organism. However, lipoprotein e (P4) is also involved in the
      utilization of NAD and NMN. Some reports have concluded that the reported heme
      related growth defect actually reflects a growth defect for NAD. In the current
      study, hel insertion mutants were constructed and a role for e (P4) in heme
      acquisition was demonstrated independent of its role in NAD or NMN acquisition.
      In addition, a rat model of infection demonstrated a role for e (P4) in the
      pathogenesis of invasive disease.

PMID- 17548225
TI  - Effects of ultrasonic frequency and liquid height on sonochemical efficiency of
      large-scale sonochemical reactors.
AB  - The sonochemical efficiency of a cylindrical sonochemical reactor has been
      investigated as a function of frequency and liquid height. The irradiation
      frequencies were 45, 129, 231 and 490 kHz. The liquid height was varied from 10
      to 700 mm. The sonochemical efficiency of the cylindrical reactor was evaluated
      by potassium iodide (KI) dosimetry and calorimetry. In our study, the
      sonochemical efficiency depended on the frequency and liquid height; further, the
      plots of sonochemical efficiency against liquid height exhibit one or two peaks
      for each frequency. The sonochemical efficiency up to the first peak increased
      monotonically with the logarithm of the frequency, and the liquid height for the
      first peak was inversely proportional to the frequency. From these results, the
      optimum frequency for a sonochemical reactor can be determined if the liquid
      height is specified for scale-up of the sonochemical reactor.

PMID- 17548226
TI  - Physiology and pathology of eye-head coordination.
AB  - Human head movement control can be considered as part of the oculomotor system
      since the control of gaze involves coordination of the eyes and head. Humans show
      a remarkable degree of flexibility in eye-head coordination strategies,
      nonetheless an individual will often demonstrate stereotypical patterns of eye
      head behaviour for a given visual task. This review examines eye-head
      coordination in laboratory-based visual tasks, such as saccadic gaze shifts and
      combined eye-head pursuit, and in common tasks in daily life, such as reading.
      The effect of the aging process on eye-head coordination is then reviewed from
      infancy through to senescence. Consideration is also given to how pathology can
      affect eye-head coordination from the lowest through to the highest levels of
      oculomotor control, comparing conditions as diverse as eye movement restrictions
      and schizophrenia. Given the adaptability of the eye-head system we postulate
      that this flexible system is under the control of the frontal cortical regions,
      which assist in planning, coordinating and executing behaviour. We provide
      evidence for this based on changes in eye-head coordination dependant on the
      context and expectation of presented visual stimuli, as well as from changes in
      eye-head coordination caused by frontal lobe dysfunction.

PMID- 17548227
TI  - Cancer therapy: new drugs are emerging based on molecular targeting but still
      many challenges.

PMID- 17548228
TI  - The G2/M checkpoint phosphatase cdc25C is located within centrosomes.
AB  - cdc25C is a phosphatase which regulates the activity of the mitosis promoting
      factor cyclin B/cdk1 by dephosphorylation, thus triggering G(2)/M transition. The
      activity and the sub-cellular localisation of cdc25C are regulated by
      phosphorylation. It is well accepted that cdc25C has to enter the nucleus to
      activate the cyclin B/cdk1 complex at G(2)/M transition. Here, we will show that
      cdc25C is located in the cytoplasm at defined dense structures, which according
      to immunofluorescence analysis, electron microscopy as well as biochemical
      subfractionation, are proven to be the centrosomes. Since cyclin B and cdk1 are
      also located at the centrosomes, this subfraction of cdc25C might participate in
      the control of the onset of mitosis suggesting a further role for cdc25C at the
      centrosomes.

PMID- 17548229
TI  - Deconstructing episodic memory with construction.
AB  - It has recently been observed that the brain network supporting recall of
      episodic memories shares much in common with other cognitive functions such as
      episodic future thinking, navigation and theory of mind. It has been speculated
      that 'self-projection' is the key common process. However, in this Opinion
      article, we note that other functions (e.g. imagining fictitious experiences) not
      explicitly connected to either the self or a subjective sense of time, activate a
      similar brain network. Hence, we argue that the process of 'scene construction'
      is better able to account for the commonalities in the brain areas engaged by an
      extended range of disparate functions. In light of this, we re-evaluate our
      understanding of episodic memory, the processes underpinning it and other related
      cognitive functions.

PMID- 17548230
TI  - Teachers in the wild: some clarification.

PMID- 17548231
TI  - The gateway hypothesis of rostral prefrontal cortex (area 10) function.
AB  - Rostral prefrontal cortex (PFC) is a large brain region, and is unusually large
      in humans. Therefore, it seems likely that it might support functions that are
      central to cognition. However, until recently, almost nothing was known about
      what these functions might be. The 'gateway hypothesis' places these abilities at
      the centre of human mental processing. It maintains that rostral PFC supports
      mechanisms that enable us to attend, to a novel degree, either to environmental
      stimuli, or by contrast, to self-generated or maintained representations (i.e.
      the 'thoughts in our head'). In this way, investigations into the functions of
      rostral PFC will reveal key new insights into how human and non-human mental
      abilities differ.

PMID- 17548232
TI  - The proactive brain: using analogies and associations to generate predictions.
AB  - Rather than passively 'waiting' to be activated by sensations, it is proposed
      that the human brain is continuously busy generating predictions that approximate
      the relevant future. Building on previous work, this proposal posits that
      rudimentary information is extracted rapidly from the input to derive analogies
      linking that input with representations in memory. The linked stored
      representations then activate the associations that are relevant in the specific
      context, which provides focused predictions. These predictions facilitate
      perception and cognition by pre-sensitizing relevant representations. Predictions
      regarding complex information, such as those required in social interactions,
      integrate multiple analogies. This cognitive neuroscience framework can help
      explain a variety of phenomena, ranging from recognition to first impressions,
      and from the brain's 'default mode' to a host of mental disorders.

PMID- 17548233
TI  - Cross-frequency coupling between neuronal oscillations.
AB  - Electrophysiological recordings in animals, including humans, are modulated by
      oscillatory activities in several frequency bands. Little is known about how
      oscillations in various frequency bands interact. Recent findings from the human
      neocortex show that the power of fast gamma oscillations (30-150Hz) is modulated
      by the phase of slower theta oscillations (5-8Hz). Given that this coupling
      reflects a specific interplay between large ensembles of neurons, it is likely to
      have profound implications for neuronal processing.

PMID- 17548234
TI  - Exploring biologically relevant chemical space with metal complexes.
AB  - Altering biological processes with small synthetic molecules is a general
      approach for the design of drugs and molecular probes. Medicinal chemistry and
      chemical biology are focused predominately on the design of organic molecules,
      whereas inorganic compounds find applications mainly for their reactivity (e.g.
      cisplatin as a DNA-reactive therapeutic) or imaging properties (e.g. gadolinium
      complexes as MRI diagnostics). In such inorganic pharmaceuticals or probes,
      coordination chemistry in the biological environment or at the target site lies
      at the heart of their modes of action. However, past and very recent results
      suggest that it is also worth exploring a different aspect of metal complexes:
      their ability to form structures with unique and defined shapes for the design of
      'organic-like' small-molecule probes and drugs. In such metal-organic compounds,
      the metal has the main purpose to organize the organic ligands in three
      dimensional space. It is likely that such an approach will complement the
      molecular diversity of organic chemistry in the quest for the discovery of
      compounds with superior biological activities.

PMID- 17548235
TI  - Solving chemical problems through the application of evolutionary principles.
AB  - Molecular evolution has been widely applied in the laboratory to generate novel
      biological macromolecules. The principles underlying evolution have more recently
      been used to address problems in the chemical sciences, including the discovery
      of functional synthetic small molecules, catalysts, materials and new chemical
      reactions. The application of these principles in dynamic combinatorial chemistry
      and in efforts involving small molecule-nucleic acid conjugates has facilitated
      the evaluation of large numbers of candidate structures or reactions for desired
      characteristics. These early efforts suggest the promise of pairing evolutionary
      approaches with synthetic chemistry.

PMID- 17548236
TI  - Aptasensors for biosecurity applications.
AB  - Nucleic acid (aptasensors) have found steadily increased utility and application
      over the past decade. In particular, aptamers have been touted as a valuable
      complement to and, in some cases, replacement for antibodies owing to their
      structural and functional robustness as well as their ease in generation and
      synthesis. They are thus attractive for biosecurity applications (e.g. pathogen
      detection) and are especially well suited because their in vitro generation
      process does not require infection of any host systems. Herein we provide a brief
      overview of the aptamers generated against pathogens and toxins over the past few
      years. In addition, a few recently described detection platforms using aptamers
      and potentially suitable applications for biosecurity will be discussed.

PMID- 17548237
TI  - Peptidic catalysts developed by combinatorial screening methods.
AB  - In recent years, oligopeptides have been developed as efficient catalysts for a
      range of important organic reactions, including acylation, silylation, oxidation,
      ester hydrolysis and aldol reactions. With many peptidic catalysts, high yields
      and chiral induction can be achieved under mild reaction conditions. Discovery
      and optimization of these catalysts typically involves the testing of compound
      collections and is therefore strongly linked to advances in combinatorial
      screening methods. This review summarizes recent developments in the field of
      catalytically active short-chain peptides, highlighting the combinatorial
      techniques that have facilitated their discovery.

PMID- 17548238
TI  - Molecular diversity in engineered protein libraries.
AB  - Engineered protein libraries, defined here as a collection of different mutant
      variants of a single specific protein, are intentionally designed to be rich in
      molecular diversity and can span ranges from as little as 400 different variants
      to greater than 10(12) members per library. The goal of engineering libraries is
      to generate new protein variants, identified upon screening, that possess desired
      novel properties. Exploitation of the natural organization of the genetic code
      has led to 'focused' libraries that are lower in overall complexity yet biased
      towards variants with preferred biophysical properties. An emerging trend, in
      which computational algorithms are blended with in vivo screens, is also leading
      towards greater and more rapid success in the field of protein design.

PMID- 17548239
TI  - Mining enzymes from extreme environments.
AB  - Current advances in metagenomics have revolutionized the research in fields of
      microbial ecology and biotechnology, enabling not only a glimpse into the
      uncultured microbial population and mechanistic understanding of possible
      biogeochemical cycles and lifestyles of extreme organisms but also the high
      throughput discovery of new enzymes for industrial bioconversions. Nowadays, the
      genetic and enzymatic differences across the gradients from 'neutral and
      pristine' to 'extreme and polluted' environments are well documented. Yet,
      extremophilic organisms are possibly the least well understood because our
      ability to study and understand their metabolic potential has been hampered by
      our inability to isolate pure cultures. There are at least two obstacles for
      reaping the fruit of the microbial diversity of extremophiles: first, in spite of
      the recent progress in development of new culturing techniques most extremophiles
      cannot be cultured using traditional culturing technologies; and second, the
      problem of the very low biomass densities often occurs under the conditions
      hostile for life, which often do not yield enough DNA and reduces the
      effectiveness of cloning.

PMID- 17548240
TI  - Bioengineering novel in vitro metabolic pathways using synthetic biology.
AB  - Huge numbers of enzymes have evolved in nature to function in aqueous
      environments at moderate temperatures and neutral pH. This gives us, in
      principle, the unique opportunity to construct multistep reaction systems of
      considerable catalytic complexity in vitro. However, this opportunity is rarely
      exploited beyond research scale, because such systems are difficult to assemble
      and to operate productively. Recent advances in DNA synthesis, genome
      engineering, high-throughput analytics, model-based analysis of biochemical
      systems and (semi-)rational protein engineering suggest that we have all the
      tools available to rationally design and efficiently operate such systems of
      enzymes, and finally harvest their potential for preparative syntheses.

PMID- 17548241
TI  - RNA structure: bioinformatic analysis.
AB  - The range of functions ascribed to RNA molecules has grown considerably during
      recent years. Consequently, the analysis and comparison of RNA sequences have
      become recurrent tasks in molecular biology. Because the biological function of
      an RNA is expressed more by its folded architecture than by its sequence,
      original computational tools adapted to the multifaceted RNA functions have to be
      developed. Such tools, recently published, enable a user to solve classical
      problems related to RNA research: constructing 'structural' multiple alignments,
      inferring complete structures and structural motifs from RNA alignments, or
      searching structural homology in genomic databases.

PMID- 17548242
TI  - Studies of interaction of emodin and DNA in the presence of ethidium bromide by
      spectroscopic method.
AB  - Emodin interacting with deoxyribonucleic acid (DNA) has been studied by different
      spectroscopic techniques, such as fluorescence, ultraviolet and visible (UV-vis),
      and fourier transform infared (FT-IR) spectroscopies, using ethidium bromide (EB)
      as a fluorescence probe of DNA. The decrease in the fluorescence of DNA-EB system
      on addition of emodin shows that the fluorescence quenching of DNA-EB complex by
      emodin occurs. The binding constants of emodin with DNA in the presence of EB are
      6.02x10(4), 9.20x10(4) and 1.17x10(5)Lmol(-1) at 20, 35 and 50 degrees C,
      respectively. FT-IR spectrum further suggests that both the phosphate groups and
      the bases of DNA react with emodin. The reaction of DNA with emodin in the
      presence of EB is affected by ionic strength and temperature. The values of
      melting temperature (T(m)) of DNA-EB complex and emodin-DNA-EB complexes were
      determined, respectively. From the experiment evidences, the major binding mode
      of emodin with DNA should be the groove binding.

PMID- 17548243
TI  - Effect of sertraline on symptoms and survival in patients with advanced cancer,
      but without major depression: a placebo-controlled double-blind randomised trial.
AB  - BACKGROUND: Depression, anxiety, fatigue, and impaired wellbeing are common,
      important, and closely related in advanced cancer. We aimed to identify the
      effects of an established antidepressant on these symptoms and survival in
      patients with advanced cancer who did not have major depression as assessed by
      clinicians. METHODS: Between July, 2001, and February, 2006, 189 patients with
      advanced cancer were randomly assigned sertraline 50 mg (n=95), or placebo
      (n=94), once per day. The primary outcome was depression as assessed by the
      Centre for Epidemiologic Studies Depression scale (CES-D); the main secondary
      outcomes were: anxiety as assessed by Hospital Anxiety and Depression Scales
      (HADS-A); overall quality of life and fatigue as assessed by Functional
      Assessment of Cancer Therapy General and Fatigue scales (FACT-G and FACT-F,
      respectively); and clinicians' ratings of quality of life by use of Spizter's
      Quality of Life Index (SQLI). Multiple measures were used for corroboration of
      the most important outcomes. Primary analyses were done by intention to treat and
      were based on scale scores at 4 weeks and 8 weeks. The benefits of sertraline
      compared with placebo are expressed on a range from +100 (ie, maximum benefit) to
      -100 (ie, maximum harm); a difference of 10 was deemed clinically significant.
      This clinical trial is registered at Current Controlled Trials website
      http://www.controlled-trials.com/ISRCTN72466475. FINDINGS: Sertraline had no
      significant effect (scale, benefit over placebo [95% CI]) on depression (CES-D
      0.4 [-2.6 to 3.4]), anxiety (HADS-A 2.0 [-1.5 to 5.5]), fatigue (FACT-F 0.3 [-4.3
      to 4.9]), overall quality of life (FACT-G 1.7 [-1.3 to 4.7]), or clinicians'
      ratings (SQLI 2.0 [-2.5 to 6.5]), and the 95% CI ruled out a clinically
      significant benefit for all main outcomes. Sertraline was discontinued more often
      and earlier than was placebo (hazard ratio 1.46 [1.03-2.06], p=0.03). Recruitment
      was stopped after the first planned interim analysis in February 2006 (n=150)
      showed that survival was longer in patients assigned placebo than in patients
      assigned sertraline (unadjusted hazard ratio 1.60 [95% CI 1.04-2.45], log-rank
      p=0.04; adjusted hazard ratio 1.62 [1.06-2.41], Cox model p=0.02). However, at
      the final analysis in July 2006 of all patients (n=189) and with longer follow
      up, survival did not differ significantly between the treatment groups
      (unadjusted hazard ratio 1.35 [0.95-1.91], log-rank p=0.09; adjusted hazard ratio
      1.27 [0.87-1.84], Cox model p=0.20). The trial was closed because it had ruled
      out a significant benefit of sertraline. INTERPRETATION: Sertraline did not
      improve symptoms, wellbeing, or survival in patients with advanced cancer who do
      not have major depression, and should be reserved for those with a proven
      indication.

PMID- 17548244
TI  - ERCP in acute pancreatitis.
AB  - BACKGROUND: The role of endoscopic retrograde cholangiopancreatography (ERCP) in
      the management of acute pancreatitis has evolved over years since its
      introduction in 1968. Its importance in diagnosing the etiology of pancreatitis
      has steadily declined with the advent of less invasive diagnostic tools. The
      therapeutic implications of ERCP in acute pancreatitis are many fold and are
      directed towards management of known etiological factors or its related
      complications. This article highlights the current status of ERCP in acute
      pancreatitis. DATA SOURCES: An English literature search using PubMed database
      was conducted on ERCP in acute pancreatitis, the etiologies and complications of
      pancreatitis amenable to endotherapy and other related subjects, which were
      reviewed. RESULTS: ERCP serves as a primary therapeutic modality for management
      of biliary pancreatitis in specific situations, pancreatitis due to
      microlithiasis, specific types of sphincter of Oddi dysfunction, pancreas
      divisum, ascariasis and malignancy. In recurrent acute pancreatitis and
      smoldering pancreatitis it has a definite therapeutic utility. Complications of
      acute pancreatitis including pancreatic-duct disruptions or leaks, benign
      pancreatic-fluid collections and pancreatic necrosis can be beneficially dealt
      with. Intraductal ultrasound and pancreatoscopy during ERCP are useful in
      detecting pancreatic malignancy. CONCLUSIONS: The role of ERCP in acute
      pancreatitis is predominantly therapeutic and occasionally diagnostic. Its role
      in the management continues to evolve and advanced invasive procedures should be
      undertaken only in centers dedicated to pancreatic care.

PMID- 17548245
TI  - Specific molecular markers in hepatocellular carcinoma.
AB  - BACKGROUND: The carcinogenesis of hepatocellular carcinoma (HCC) is a multi
      factorial, multistep and complex process. Its prognosis is poor, and early
      diagnosis and monitoring metastasis of HCC is of the utmost importance.
      Circulating diagnostic and prognostic biomarkers could be used in proper
      postoperative treatment of patients at an early stage of HCC development. This
      review summarizes recent studies of the specific biomarkers in diagnosis and
      monitoring metastasis or postoperative recurrence of HCC. DATA SOURCES: An
      English-language literature search was conducted using MEDLINE (June 1998 to
      September 2006) on researches of some valuable specific biomarkers in diagnosis
      and monitoring metastasis or postoperative recurrence of HCC. RESULTS: Hepatoma
      tissues can synthesize various tumor-related proteins, polypeptides, and
      isoenzymes, such as alpha-fetoprotein (AFP), hepatoma-specific gamma-glutamyl
      transpeptidase (HS-GGT), etc, and then secrete into blood. The valuable early
      diagnostic and prognostic biomarkers could predict the development and metastases
      of HCC. Recent researches have confirmed that circulating hepatoma-specific AFP
      subfraction, transforming growth factor (TGF)-beta1, HS-GGT, and free insulin
      like growth factor (IGF)-II may be more specific markers than total AFP level for
      early diagnosis for HCC. The circulating genetic markers such as AFP-mRNA, TGF
      beta1-mRNA, IGF-II-mRNA, etc from peripheral blood mononuclear cells of HCC
      patients have been most extensively used in monitoring distal metastasis or
      postoperative recurrence of HCC. CONCLUSIONS: Hepatoma tissues synthesize and
      secrete valuable molecular markers into blood. The analyses of circulating
      hepatoma-specific biomarkers are useful to early diagnosis of HCC or monitoring
      metastasis or postoperative recurrence of HCC.

PMID- 17548246
TI  - The role of liver transplantation for hilar cholangiocarcinoma.
AB  - BACKGROUND: Hilar cholangiocarcinoma is a devastating disease. Surgery is the
      only potentially curative modality. However, the results of surgical resection
      for hilar cholangiocarcinomas are disappointing. The introduction of liver
      transplantation for this condition has brought new hope for the management of
      this disease. The aim of this review is to discuss the role of liver
      transplantation in this disease. DATA SOURCES: A MEDLINE search was conducted for
      the articles on liver transplantation for hilar cholangiocarcinoma. Their results
      have been compiled and compared with the existing literature on resection for
      this disease. RESULTS: The earlier series on liver transplantation for hilar
      cholangiocarcinoma were not encouraging because of poor patient selection. The
      Mayo Clinic protocol of neoadjuvant chemoradiation followed by liver
      transplantation has shown remarkable success (survival at 1-, 3-, and 5-year post
      transplantation being 92%, 82%, and 82%, respectively). With better patient
      selection and integration of neoadjuvant chemoradiation, the long-term survival
      is superior to that of the patients who undergo resection, as shown by the
      published literature on resection. The limitations of organ availability can be
      overcome by the living donor liver transplantation programme. This review article
      discusses the rationale, pros and cons of liver transplantation vis-a-vis
      resection for hilar cholangiocarcinoma. CONCLUSIONS: Liver transplantation,
      especially living donor liver transplantation, is a new and exciting alternative
      to resection for hilar cholangiocarcinoma. Integration of neoadjuvant
      chemoradiation has the potential to further improve the curative potential of
      liver transplantation. The strategy of combining neoadjuvant chemoradiation and
      liver transplantation brings new hope for the treatment of this difficult
      disease.

PMID- 17548247
TI  - No association exists between E-cadherin gene polymorphism and tumor recurrence
      in patients with hepatocellular carcinoma after transplantation.
AB  - BACKGROUND: E-cadherin is an epithelial cell adhesion molecule, and decreased E
      cadherin expression in liver cancer is associated with poor prognosis. A -160 C-
      >A polymorphism in the promoter region of E-cadherin has been reported to
      decrease gene transcription. This allelic variation may be a potential genetic
      marker for identifying those individuals at higher risk for invasive/metastatic
      disease. METHODS: The effect of E-cadherin gene polymorphism on risk of tumor
      recurrence was studied in 93 patients with hepatocellular carcinoma (HCC) after
      liver transplantation, and determined whether this polymorphism is a biomarker
      for the risk of tumor recurrence. RESULTS: The genotype frequencies in the
      patients with recurrence were C/C: 0.667, C/A: 0.311, and A/A: 0.022, and in the
      patients without recurrence C/C: 0.604, C/A: 0.271 and A/A: 0.125. No significant
      difference was found between the two groups (P=0.171). Between -160 C-->A
      polymorphism and the clinicopathological data, there were no statistically
      significant differences in the distribution of the parameters as to age, gender,
      portal vein tumor thrombi, preoperative alpha-fetoprotein level, tumor size, or
      histopathological grading (P>0.05). CONCLUSION: The results of this study show no
      association exists between the E-cadherin genotype and the risk of tumor
      recurrence in Chinese patients with HCC.

PMID- 17548248
TI  - Transarterial chemoembolization using degradable starch microspheres and iodized
      oil in the treatment of advanced hepatocellular carcinoma: evaluation of tumor
      response, toxicity, and survival.
AB  - BACKGROUND: In a multidisciplinary conference patients with advanced non
      resectable hepatocellular carcinoma (HCC) were stratified according to their
      clinical status and tumor extent to different regional modalities or to best
      supportive care. The present study evaluated all patients who were stratified to
      repeated transarterial chemoembolization (TACE) from 1999 until 2003 in terms of
      tumor response, toxicity, and survival. A moderate embolizing approach was chosen
      using a combination of degradable starch microspheres (DSM) and iodized oil
      (Lipiodol) in order to combine anti-tumoral efficiency and low toxicity. METHODS:
      Fourty-seven patients were followed up prospectively. TACE treatment consisted of
      cisplatin (50 mg/m(2)), doxorubicin (50 mg/m(2)), 450-900 mg DSM, and 5-30 ml
      Lipiodol. DSM and Lipiodol were administered according to tumor vascularization.
      Patient characteristics, toxicity, and complications were outlined. In
      multivariate regression analyses of pre-treatment variables from a prospective
      database, predictors for tumor response and survival after TACE were determined.
      RESULTS: 112 TACE courses were performed (2.4+/-1.5 courses per patient). Mean
      maximum tumor size was 75 (+/-43) mm, in 68% there was bilobar disease. Best
      response to TACE treatment was: progressive disease (PD) 9%, stable disease (SD)
      55%, partial remission (PR) 36%, and complete remission (CR) 0%. Multivariate
      regression analyses identified tumor size <or=75 mm, tumor number <or=5, and
      tumor hypervascularization as predictors for PR. The overall 1-, 2-, and 3-year
      survival rates were 75%, 59%, and 41%, respectively, and the median survival was
      26 months. Low alpha-fetoprotein levels (<400 ng/ml) (Odds ratio=3.3) and PR as
      best response to TACE (Odds ratio=6.7) were significantly associated with long
      term survival (>30 months, R(2)=36%). Grade 3 toxicity occurred in 7.1% (n=8),
      and grade 4 toxicity in 3.6% (n=4) of all courses in terms of reversible
      leukopenia and thrombocytopenia. The incidence of major complications was 5.4%
      (n=6). All complications were managed conservatively. The mortality within 6
      weeks after TACE was 2.1% (one patient). CONCLUSIONS: DSM and Lipiodol were
      combined successfully in the palliative TACE treatment of advanced HCC resulting
      in high rates of tumor response and survival at limited toxicity. Favourable
      tumor response was associated with tumor extent and vascularization. TACE using
      DSM and Lipiodol can be considered a suitable palliative measure in patients who
      might not tolerate long acting embolizing agents.

PMID- 17548249
TI  - Hepatectomy after primary repair of ruptured liver cancer.
AB  - BACKGROUND: Spontaneous rupture of liver tumor is often considered a potentially
      life-threatening situation. The aim of the present study was to assess re
      operation after emergency repair of ruptured liver cancer. METHODS: We reviewed
      retrospectively five patients who had been admitted within a one-year period and
      undergone a second operation after emergency repair of primary liver cancer
      rupture. RESULTS: Five patients (4 males and 1 female) underwent emergency repair
      of ruptured liver cancer in local hospitals; three of them received transarterial
      chemoembolization (TACE). The tumor was in the right hepatic lobe in 2 patients,
      middle lobe in 1, left median lobe (segment IV) in 1, and caudate lobe (segment
      I) in 1. Operative methods included right hemihepatectomy in 2 patients, left
      partial lobectomy or wedge resection in 1, caudate lobe resection in 1, and
      middle lobctomy+cholecystectomy+abdominal implant resection in 1. Intra-abdominal
      chemotherapy was given to all 5 patients. Follow-up showed that one patient died
      from intrahepatic metastasis and hepatic failure six months after re-operation
      and that two patients died from extensive intra-abdominal metastases six months
      later. The remaining two patients have been surviving for 28 months. CONCLUSIONS:
      Re-operation is indicated for patients with primary liver cancer rupture whose
      liver function is good and whose foci are localized and operable. Apart from
      removing the primary foci, it is necessary to clear abdominal metastatic foci,
      irrigate the abdomen and administer chemotherapy to prolong the patient's life.

PMID- 17548250
TI  - Diagnosis of bacterial hepatic abscess by CT.
AB  - BACKGROUND: Bacterial hepatic abscess usually is acute and progressive, often
      resulting in sepsis, impairment of liver function and disseminated intravascular
      coagulation. The mortality rate was as high as 80% in the past. For the purpose
      of early diagnosis and differential diagnosis of this disease, we probed the
      imaging manifestations and their characteristics in bacterial hepatic abscesses
      by CT scan. METHODS: Twenty-four lesions from 21 patients with bacterial hepatic
      abscesses that were confirmed by clinical features, puncture and culture were
      reviewed for CT manifestations. Fourteen patients were male and 7 were female,
      with an average age of 56.2 years. All lesions underwent CT plain scan and three
      phase enhanced scan and 15 patients underwent delayed-phase imaging. Three senior
      radiologists read the films in accordance with a standard. RESULTS: Among 24
      lesions, 18 (75%) were situated in the right liver with diameters of 1.4-9.3 cm
      (average 4.5 cm). Nineteen (79.2%) lesions were round or sub-round in shape, and
      22 (91.7%) had smooth, uninterrupted and sharp edges. All lesions showed low
      attenuation of less than 20 Hu. Twenty-two enhanced lesions (91.7%) had rim
      shaped enhancement in the abscess wall, and 13 (54.2%) showed single or double
      ring signs. Eighteen (75%) displayed honeycomb-like, grid-like or strip-like
      enhancement. Eighteen (75%) were regionally enhanced in the surroundings or upper
      or lower layers. Only 2 (8.3%) displayed a gas-liquid surface sign. CONCLUSIONS:
      The CT findings of bacterial hepatic abscess are usually typical, and the
      diagnosis of the abscess is not difficult. To precisely diagnose atypical cases,
      it is necessary to combine CT with clinical observations and follow-up.

PMID- 17548251
TI  - Effect of Sirpalpha1 on the expression of nuclear factor-kappa B in
      hepatocellular carcinoma.
AB  - BACKGROUND: Signal regulatory protein alpha1 (Sirpalpha1) is a member of Sirps
      families containing four immunoreceptor tyrosine-based inhibitory motifs (ITIMs)
      domains in the cytoplasm of and an activated substrate of receptor tyrosine
      kinase (RTK), that negatively regulates the RTK-dependent cell proliferating
      signal transduction pathway. Previously we found that Sirpalpha1 was closely
      associated with the occurrence and development of hepatocellular carcinoma (HCC)
      as well as liver regeneration. Since it is unclear about the regulatory
      mechanisms, we established the cell line transfected Sirpalpha1 gene and
      preliminarily clarified the mechanisms by which Sirpalpha1 negatively regulates
      the carcinogenesis and development of HCC. METHODS: Liver cancer Sk-Hep1 cell was
      respectively transfected with plasmids of pLXSN, pLXSN-Sirpalpha1 and pLXSN
      Sirpalpha1delta4Y2, screened with the drug of G418 (1200 microg/ml), and various
      transfected Sk-Hep1 cell lines were obtained. The protein expressions of P65,
      P50, IkappaBalpha, cyclin D1 and Fas in various Sk-Hep1 cell lines were
      determined by Western blotting, and P65 and P50 were localized by the
      immunofluorescence technique. RESULTS: Sirpalpha1 could significantly upregulate
      the protein expression of IkappaBalpha (vs. other cell lines, P<0.05) in the Sk
      Hep1 cell, and downregulate the protein expressions of P65, P50 and cyclin D1
      (vs. other cell lines, P<0.05) in the Sk-Hep1 cell. P65 protein expression was
      mainly localized in the cytoplasm in the pLXSN Sk-Hep1 cell, and in the nucleus
      of the Sk-Hep1 cell with mutant Sirpalpha1delta4Y2, but in nucleus of the Sk-Hep1
      cell with wild Sirpalpha1. P50 protein expression was localized in the cytoplasm
      and nucleus of the pLXSN Sk-Hep1 cell, but in the nucleus of the Sk-Hep1 cell
      with wild Sirpalpha1 and mutant Sirpalpha1delta4Y2 plasmid. CONCLUSIONS:
      Sirpalpha1 might negatively regulate and control the abnormal proliferation of
      liver cancer cells by influencing the protein content and localization of nuclear
      factor-kappa B, then influence the expression of cyclins such as cyclin D1 in the
      signal transduction pathway. It may be one of the important mechanisms by which
      Sirpalpha1 negatively regulates the carcinogenesis and development of HCC.

PMID- 17548252
TI  - N-acetylcysteine inhibits activation of toll-like receptor 2 and 4 gene
      expression in the liver and lung after partial hepatic ischemia-reperfusion
      injury in mice.
AB  - BACKGROUND: Toll-like receptor 2 and 4 (TLR2/4) may play important roles in
      ischemia-reperfusion (I/R) injury, and N-acetylcysteine (NAC) can prevent the
      generation of reactive oxygen species (ROS) induced by I/R injury. This study
      aimed to investigate the changes in TLR2/4 gene expression in the liver and lung
      after I/R injury with or without NAC pretreatment. METHODS: BALB/c mice were used
      in a model of partial hepatic I/R injury and randomly assigned to a sham-operated
      control group (SH), a hepatic ischemia/reperfusion group (I/R) or a NAC
      pretreated, hepatic I/R group (I/R-NAC). The levels of TNF-alpha in the portal
      vein and plasma alanine aminotransferase (ALT) were measured at 1 and 3 hours
      after reperfusion. The lung wet-to-dry ratio was measured, and the expression of
      TLR2/4 mRNA and protein in the liver and lung were assessed with RT-PCR and
      Western blotting at the same time points. RESULTS: Compared with the I/R group,
      the expression of TLR2/4 mRNA and protein in the liver and lung in the I/R-NAC
      group was decreased at the same time point (P<0.05). The levels of portal vein
      TNF-alpha and plasma ALT increased continuously in the I/R group at 1 and 3 hours
      of reperfusion compared with the SH group; however, they declined significantly
      in the group pretreated with NAC (P<0.05). The extent of lung edema was relieved
      in the I/R-NAC group compared with the I/R group (P<0.05). CONCLUSIONS: TLR2/4
      was activated in the liver and lung in the process of partial hepatic I/R injury.
      NAC inhibited the activation of TLR2/4 and the induction of TNF-alpha resulting
      from I/R injury via modulating the redox state, thus it may mitigate liver and
      lung injury following partial hepatic I/R in mice.

PMID- 17548253
TI  - Identification of genes upregulated by recombinant interferon-alpha in HepG2
      cells by suppressive subtractive hybridization analysis.
AB  - BACKGROUND: Interferon-alpha (IFN-alpha) is an important cytokine with multiple
      functions, but the target genes transactivated by IFN-alpha remain largely
      unknown. A study of such genes will help to understand the mechanism of function
      of IFN-alpha. To isolate the gene transcripts specifically upregulated by IFN
      alpha in HepG2 cells, we conducted suppressive subtractive hybridization (SSH)
      analysis. METHODS: SSH was used to analyze the target genes transactivated by
      recombinant IFN-alpha protein, and a subtractive cDNA library was constructed
      from HepG2 cells treated with recombinant IFN-alpha (rIFN-alpha, 2000 IU/ml) for
      16 hours as tester, and cells not treated with rIFN-alpha as driver. The SSH PCR
      products from the library were cloned into pGEM-T easy vector and with BLASTX,
      the positive clones were randomly selected, sequenced and compared to the
      database in GenBank of the 35 differentially expressed gene fragments from the
      library, 6 clones showed significant homology to other known proteins. RESULTS:
      The subtractive cDNA library of genes upregulated by IFN-alpha was constructed
      successfully. rIFN-alpha upregulated the expression of the RAN binding protein 5
      (RANBP5), NADH dehydrogenase, exosome component 3 (EXOSC3), zinc finger RNA
      binding protein, Dickkopf homolog 1 (DKK1) and acetyl-coenzyme A
      acetyltransferase 2 (ACAT2). CONCLUSIONS: These results suggest that rIFN-alpha
      can upregulate the expression of important genes to exert its functions, and
      provide new clues for discovering the molecular mechanisms of action of IFN
      alpha.

PMID- 17548254
TI  - Pseudoaneurysm following laparoscopic cholecystectomy.
AB  - BACKGROUND: Laparoscopic cholecystectomy (LC) is the operation of choice for
      removal of the gallbladder. Unrecognized bile duct injuries present with biliary
      peritonitis and systemic sepsis. Bile has been shown to cause damage to the
      vascular wall and therefore delay the healing of injured arteries leading to
      pseudoaneurysm formation. Failure to deal with bile leak and secondary infection
      may result in pseudoaneurysm formation. This study was to report the incidence
      and outcomes of pseudoaneurysm in patients with bile leak following LC referred
      to our hospital. METHODS: A retrospective analysis of our prospectively
      maintained liver database using key words pseudoaneurysm, bile leak and bile duct
      injury following laparoscopic cholecystectomy from January 2000 to December 2005
      was performed. RESULTS: A total of 86 cases were referred with bile duct injury
      and bile leak following LC and of these, 4 patients (4.5%) developed hepatic
      artery pseudoaneurysm (HAP) presenting with haemobilia in 3 and massive intra
      abdominal bleed in 1. Selective visceral angiography confirmed pseudoaneurysm of
      the right hepatic artery in 2 cases, cystic artery stump in one and an intact but
      ectatic hepatic artery with surgical clips closely applied to the right hepatic
      artery at the origin of the cystic artery in the fourth case. Effective
      hemostasis was achieved in 3 patients with coil embolization and the fourth
      patient required emergency laparotomy for severe bleeding and hemodynamic
      instability due to a ruptured right hepatic artery. Of the 3 patients treated
      with coil embolization, 2 developed late strictures of the common hepatic duct
      (CHD) requiring hepatico-jejunostomy and one developed a stricture of left
      hepatic duct. All the 4 patients are alive at a median follow up of 17 months
      (range 1 to 65) with normal liver function tests. CONCLUSIONS: HAP is a rare and
      potentially life-threatening complication of LC. Biloma and subsequent infection
      are reported to be associated with pseudoaneurysm formation. Late duct stricture
      is common either due to unrecognized injury at LC or secondary to ischemia after
      embolization.

PMID- 17548255
TI  - Relationship between intraduodenal peri-ampullary diverticulum and biliary
      disease in 178 patients undergoing ERCP.
AB  - BACKGROUND: The presence of intraduodenal peri-ampullary diverticulum is often
      observed during upper digestive tract barium meal studies and endoscopic
      retrograde cholangiopancreatography (ERCP). A few papers in China and overseas
      reported that the diverticulum had something to do with the incidence of
      cholelithiasis. This study was undertaken to further test this notion and
      ascertain the relationship between intraduodenal peri-ampullary diverticulum and
      biliary disease, especially the formation of bile duct pigment stones. METHODS: A
      total of 178 patients who had undergone ERCP or endoscopic sphincterotomy (EST)
      were studied retrospectively. They were divided into 6 groups according to the
      category of biliary disease, and the incidence rates of intraduodenal peri
      ampullary diverticulum were calculated. RESULTS: There were 44 patients with
      intraduodenal peri-ampullary diverticulum in 81 patients with primary bile duct
      pigment stones (54.32%), 4 in 8 patients with bile duct stones and gallbladder
      stones (50%), 7 in 33 patients with bile duct stones secondary to gallbladder
      stones (21.21%), 3 in 21 patients with inflammation and stricture of the end of
      the bile duct and papilla (14.29%), 1 in 22 patients with carcinoma of the end of
      the bile duct and papilla (4.54%), and 5 in 13 patients with post-cholecystectomy
      syndrome or sphincter of Oddi dysfunction (38.46%). CONCLUSIONS: The incidence
      rate of intraduodenal peri-ampullary diverticulum in patients with primary bile
      duct pigment stones is higher than that in patients with bile duct stones
      secondary to gallbladder stones, patients with inflammation and stricture of the
      end of the bile duct and papilla, and patients with carcinoma of the end of the
      bile duct and papilla. These findings indicate that the anatomical abnormalities
      and malfunction of the sphincter of Oddi play an important role in the formation
      of bile duct pigment stones.

PMID- 17548256
TI  - Effects of targeting magnetic drug nanoparticles on human cholangiocarcinoma
      xenografts in nude mice.
AB  - BACKGROUND: Targeting is a new therapeutic tool for malignant tumor as a result
      of combining nanotechnology with chemotherapeutics. The aim of our study was to
      investigate the effects of magnetic nanoparticles enveloping a chemotherapeutic
      drug on human cholangiocarcinoma xenografts in nude mice. METHODS: The human
      cholangiocarcinoma xenograft model was established in nude mice with the QBC939
      cell line. The nude mice were randomly assigned to 7 groups. 0.9% saline or
      magnetic nanoparticles, including high (group 2), medium (group 4) and low (group
      5) dosages, were given to nude mice through the tail vein 20 days after the
      QBC939 cell line was implanted. Calculations were made 35 days after treatment in
      order to compare the volumes, inhibition ratios and growth curves of the tumors
      in each group. Mice in each group were sacrificed randomly to collect tumor
      tissues and other organs for electron microscopy and pathological examination.
      RESULTS: The high and medium dosage groups were significantly different from the
      control group (P<0.05). The tumor inhibition ratios for the high, medium and low
      dosage groups were 39.6%, 14.6% and 7.9%, respectively. The tumor growth curve of
      groups 5, 4, and 2 changed slowly in turn. The high and medium groups showed cell
      apoptosis under an electron microscope. CONCLUSION: Magnetic nanoparticles can
      inhibit the growth of human cholangiocarcinoma xenografts in nude mice.

PMID- 17548257
TI  - Diagnosis of pancreatic cancer by cytology and telomerase activity in exfoliated
      cells obtained by pancreatic duct brushing during endoscopy.
AB  - BACKGROUND: Telomerase activity is reported to be specific and frequent in human
      pancreatic cancer. We conducted this study to assess the usefulness of monitoring
      telomerase activity in exfoliated cells obtained by pancreatic duct brushing
      during endoscopic retrograde cholangiopancreatography (ERCP) for the diagnosis of
      pancreatic cancer. METHODS: Exfoliated cells obtained by pancreatic duct brushing
      during ERCP from 21 patients (18 with pancreatic cancer, 3 with chronic
      pancreatitis) were examined. Telomerase activity was detected by polymerase chain
      reaction and telomeric repeat amplification protocol assay (PCR-TRAP-ELISA).
      RESULTS: D450 values of telomerase activity were 0.446+/-0.2700 in pancreatic
      cancer and 0.041+/-0.0111 in chronic pancreatitis. 77.8% (14/18) of patients with
      pancreatic cancer had cells with telomerase activity. None of the samples from
      patients with chronic pancreatitis showed telomerase activity, when the cutoff
      value of telomerase activity was set at 2.0. Cytological examination showed
      cancer cells in 66.7% (12/18) of the patients. CONCLUSIONS: Telomerase activity
      may be an early malignant event in pancreatic cancer development. Cytology and
      telomerase activity in cells obtained by pancreatic duct brushing may complement
      each other for the diagnosis of pancreatic cancer.

PMID- 17548258
TI  - Effects of 5-fluouracil combined with sulfasalazine on human pancreatic carcinoma
      cell line BxPC-3 proliferation and apoptosis in vitro.
AB  - BACKGROUND: Most pancreatic carcinomas are clinically insensitive to
      chemotherapeutics. The exact mechanisms of their apoptosis and multiple drug
      resistance are obscure at present. This study was undertaken to explore the
      influence of chemotherapy on anti-proliferation, apoptosis and the cell cycle,
      and lay a fundamental basis for further research into the apoptotic mechanisms
      and prevention of multiple drug resistance in pancreatic carcinoma. METHODS: The
      human pancreatic carcinoma cell line BxPC-3 was cultured in vitro. The growth
      inhibition rate, cell cycle and apoptotic rate of cells treated with 5
      fluorouracil (5-FU), sulfasalazine alone or a combination at different
      concentrations were evaluated with the MTT method and flow cytometry. Phase
      contrast microscopy was used to observe morphological changes in the cells
      treated with 5-FU, sulfasalazine or both for 24 hours. RESULTS: The growth
      inhibition rate of the BxPC-3 cells treated with 5-FU and sulfasalazine
      significantly increased in a time- and dose-dependent manner. The growth
      inhibition rate of the cells treated with 5-FU gradually increased, but decreased
      at different concentrations of sulfasalazine for a prolonged period. The
      apoptotic rate of the BxPC-3 cells induced by sulfasalazine (200 mg/L), 5-FU (100
      mg/L) or both for 12 hours were (2.68+/-0.36)%, (6.59+/-0.90)%, and (10.52+/
      0.55)%, respectively, compared with the corresponding control values were (3.17+/
      0.08)%, (1.50+/-0.06)%, and (4.08+/-0.31)% [(t=2.33 (P>0.05), 9.78 and 17.56
      (P<0.01)]. It increased to (7.63+/-0.68)%, (40.43+/-1.79)%, and (64.69+/-0.82)%
      for 48 hours, in comparison with the control that was (29.20+/-2.18)%, (5.61+/
      0.13)%, and (12.02+/-0.52)% [t=17.06, 33.66 and 94.51 (P<0.01)]. The apoptotic
      rate, proportion of cells in S-phase and proliferative index rose after use of 5
      FU (12.5, 25, 50, 75, and 100 mg/L) alone for 24 hours. However, the apoptotic
      rate at augmented concentrations of sulfasalazine for 24 hours slowly increased
      from (1.47+/-0.08)% to (3.45+/-0.28)%, the proportion of cells in G0/G1-phase
      increased from (35.13+/-0.32)% to (54.32+/-1.45)%, the proportion of cells in S
      phase decreased from (45.37+/-1.48)% to (16.67+/-2.73)%, and the proliferative
      index gradually lowered. The proportion of G0/G1-phase cells treated by 5-FU (100
      mg/L) and sulfasalazine (200 mg/L) increased from (43.31+/-1.52)% (12 hours) to
      (85.05+/-0.24)% (48 hours) compared with the corresponding controls [t=7.93 (12
      hours), 21.30 (48 hours), P<0.01], and the proportion of cells in S-phase
      decreased from (11.63+/-1.11)% (12 hours) to (4.47+/-0.68)% (48 hours) in
      contrast to the controls [t=37.68 (12 hours), 8.60 (48 hours), P<0.01]. Most
      cells after the combined use of the two agents for 24 hours displayed pyknosis
      and oval shape by phase-contrast microscopy. The cells treated with 5-FU (100
      mg/L) for 24 hours were pyknotic and oval shaped. A few of cells in the group
      treated with sulfasalazine (200 mg/L) were pyknotic at 24 hours. CONCLUSIONS:
      Sulfasalazine may enhance the inhibitory proliferation and apoptosis effect on
      BxPC-3 cells induced by 5-FU, which is closely related to synergistically the
      cell cycle arrested in G0/G1-phase.

PMID- 17548259
TI  - Hemoperitoneum secondary to rupture of cystic artery pseudoaneurysm.
AB  - BACKGROUND: Spontaneous hemoperitoneum of hepatobiliary origin is commonly due to
      hemorrhage from a liver tumor. It is rarely caused by spontaneous rupture of
      aneurysm in visceral arteries. METHODS: We report an unusual case of
      hemoperitoneum caused by rupture of cystic artery pseudoaneurysm, and also
      outline the approach to its management through surgical and radiological methods.
      RESULTS: In our patient, the pseudoanurysm was initially treated with
      percutaneous thrombin injection. However this method of treatment failed after
      initial success. The pseudoanurysm was finally obliterated successfully using
      microcoil embolization. CONCLUSIONS: The mainstay of treatment of cystic artery
      pseudoaneurysm is cholecystectomy and ligation of the aneurysm. Recent
      publications showed success in using microcoil embolisation. In this case we also
      outline the use of percutaneous thrombin injection as a definitive treatment
      method and discuss its success or failure as a new method of treatment.

PMID- 17548260
TI  - Colonic gallstones: a case report.
AB  - BACKGROUND: Colonic gallstone is an uncommon entity with high morbidity and
      mortality due to various reasons. It remains a diagnostic challenge because of
      delayed and non-specific presentations, especially in the elderly population,
      often with multiple co-morbidities. METHOD: We present a case of 81-year-old
      woman who had a large bowel obstruction due to colonic gallstone. RESULTS:
      Immediately after a cholecysto-colonic fistula was found by laporotomy, she
      underwent a single stage enterolithotomy, cholecystectomy and fistula closure.
      CONCLUSIONS: A single stage enterolithotomy, cholecystectomy and fistula closure
      is ideal for this condition. Various other surgical options in the literature are
      discussed.

PMID- 17548261
TI  - Iatrogenic bile duct injuries from biliary tract surgery.
AB  - BACKGROUND: Cholecystectomy is the most commonly performed procedure in general
      surgery. However, bile duct injury is a rare but still one of the most common
      complications. These injuries sometimes present variably after primary surgery.
      Timely detection and appropriate management decrease the morbidity and mortality
      of the operation. METHODS: Five cases of iatrogenic bile duct injury (IBDI) were
      managed at the Department of Surgery, First Affiliated Hospital, Xi'an Jiaotong
      University. All the cases who underwent both open and laparoscopic
      cholecystectomy had persistent injury to the biliary tract and were treated
      accordingly. RESULTS: Recovery of the patients was uneventful. All patients were
      followed-up at the surgical outpatient department for six months to three years.
      So far the patients have shown good recovery. CONCLUSIONS: In cases of IBDI it is
      necessary to perform the operation under the supervision of an experienced
      surgeon who is specialized in the repair of bile duct injuries, and it is also
      necessary to detect and treat the injury as soon as possible to obtain a
      satisfactory outcome.

PMID- 17548262
TI  - Treatment of hepatic cysts by B-ultrasound-guided radiofrequency ablation.
AB  - BACKGROUND: The traditional therapy for hepatic cysts has limited success because
      of recrudescence. Radiofrequency ablation (RFA) has become popular because of its
      advantages including little damage, therapeutic effect and reduced suffering.
      This report describes the effects and reliability of RFA in the treatment of 29
      patients with hepatic cysts. METHODS: B-ultrasound-guided RFA was used to treat
      hepatic mono-cyst or multi-cysts of 29 patients (63 tumors). Ablative efficiency
      and complications were assessed by imaging and clinical symptoms. RESULTS: The
      tumors were abated completely in 34 cysts with a diameter <5 cm and no recurrence
      was seen after 3 months. In 21 cysts with a diameter of 5-10 cm, tumor volume was
      decreased by over 70%, then reduction and fiberosis were found. In 8 cysts with a
      diameter greater than 10 cm, tumor volume was decreased by more than 60%, and in
      2 cysts it was increased more slightly than that at 1 month after RFA. In
      subsequent follow-up (6 and 12 months after RFA), tumors <10 cm in diameter were
      fully ablated. No significant discomfort and complications were found in any
      patient. CONCLUSION: RFA for the treatment of hepatic cysts is safe, and free
      from complications.

PMID- 17548263
TI  - Detection of cancer clones in human colorectal adenoma as revealed by increased
      DNA instability and other bio-markers.
AB  - An immunohistochemical differential staining of cancerous cells with anti
      cytidine antibody after denaturation of nuclear DNA by acid hydrolysis with 2N
      HCl at 30 degrees C for 20 min (DNA-instability test) has been used as a marker
      for malignancy. The test was applied to bioptic tissues of human colorectal
      polyps assessed histopathologically as hyperplastic polyp (11 cases), tubular
      adenoma of mild (68 cases), moderate (102 cases), and severe (46 cases)
      dysplasia, and adenocarcinoma (30 cases). The serial sections of the same tissues
      were also subjected to immunohistochemical staining for Ki67, p53, DNA
      fragmentation factor 45 (DFF45) and vascular endothelial growth factor (VEGF).
      The DNA-instability test was positive in 30 (100%) adenocarcinoma cases, 46
      (100%) severe dysplasia adenoma cases, 36 (35.29%) moderate dysplasia adenoma
      cases, and 8 (11.76%) mild dysplasia adenoma cases, indicating malignancy. All
      hyperplastic polyps were negative to the DNA-instability test. Furthermore, the
      percentage of glands positive in the DNA-instability test steadily increased in
      going from mild (10%), to moderate (35%), to severe (100%) dysplasia, and
      adenocarcinoma (100%). All other biological markers tested in the present study
      showed significantly higher values in those adenoma glands that were positive to
      the DNA-instability test, irrespective of the dysplasia grade, as compared to the
      markers in the adenoma glands that were negative to DNA instability testing.
      Furthermore, the former values were comparable to those in adenocarcinoma. The
      results indicate that cancer cell clones are already present at the adenoma
      stages showing positivity to DNA instability testing, enhanced proliferative
      activity, p53 mutation and induction of DFF45 and VEGF, at a time when the degree
      of morphological atypia are not yet large enough for them to be identified as
      cancer. These factors promote cancer cell proliferation, produce heterogeneous
      subclones due to DNA instability, enhance their survival by escaping apoptosis,
      and provide abundant nutrients by neovascularization during the early-stage
      progression of colorectal cancer.

PMID- 17548264
TI  - Ghrelin and insulin gene expression changes in streptozotocin-induced diabetic
      rats after rosiglitazone pretreatment.
AB  - The aim of the study was to evaluate the effect of rosiglitazone treatment on
      islet ghrelin and insulin gene expressions in streptozotocin (STZ)-induced
      diabetic rats. Animals were divided into four groups. 1. Intact controls. 2.
      Rosiglitazone-treated controls. 3. STZ-induced diabetes. 4. Rosiglitazone-treated
      diabetes. Rosiglitazone was given for 7 days at a dose of 20 mg/kg body weight.
      Ghrelin and insulin gene expressions were investigated by immunohistochemistry
      and in situ hybridization. There was no statistically significant difference in
      body weight between STZ-induced diabetic rats and rosiglitazone-treated diabetic
      rats during the experimental period. Furthermore, there were no significant
      differences in blood glucose levels and insulin immunoreactive cell numbers
      between STZ-induced diabetic rats and rosiglitazone-treated diabetic rats. There
      was a tendency towards a reduction of ghrelin gene expression in diabetic animals
      compared with intact controls. We found, in addition, that ghrelin immunoreactive
      and ghrelin mRNA expressing cells were frequent in the epithelial lining of the
      ducts suggesting ductal epithelium might be the source of the regenerating islet
      ghrelin cells, as is known for other islet cells. The results show that short
      term rosiglitazone pretreatment had no significant effect on ghrelin and insulin
      gene expressions.

PMID- 17548265
TI  - Immunohistochemical profile of some neurotransmitters and neurotrophins in the
      seminiferous tubules of rats treated by lonidamine.
AB  - Lonidamine (LND) or [1-(2,4-dichlorobenzyl)-1H-indazole-3-carboxylic acid] is an
      anticancer and antispermatogenic drug that exerts a large number of effects on
      tumor cells and germ cells. Sexually mature male Sprague-Dawley rats were housed
      at 22 degrees C on a 12-h light/12-h dark cycle 1 week before the experiments,
      with free access to food and water. LND was suspended in 0.5% methylcellulose at
      a concentration of 10 mg/mL and administered orally at the dose of 10 mL/kg
      (b.w.) as a single dose. Control rats received an equal amount of vehicle. Testes
      were removed, fixed for 24 h in 2% glutaraldehyde and 2% paraformaldehyde in 0.1
      M sodium phosphate (pH 7.2 at 22 degrees C), rinsed with the same buffer, and
      stored at room temperature. From each sample, a block of tissue was removed by
      sectioning through the organ. After dehydration in ethanol at increasing
      concentrations (70-100%), each block was embedded in paraffin and serial 5 mm
      thick sections were cut using a rotatory microtome. The immunoreactivity for NTs
      has been observed in spermatogonia of untreated rats, while the rats treated with
      LND showed an immunohistochemical localization in all the stages of germinal
      cells. The generally well-expressed immunoreactivity for the neurotrophins
      receptors in treated rats observed in our study is presumably attributable to
      alterations of the receptors' structure and/or expression leading to changes of
      the activity, affinity, localization or protein interactions that may depend on
      sensitization of ion channels (induced by LND). Neurotrophins (NTs) appear to be
      interesting proteins for the modulation of sperm maturation and motility with a
      prominent role for the nerve growth factor (NGF), that may exert an autocrine or
      paracrine role. We therefore investigated the location and distribution of
      immunoreactivity for some neurotransmitters (SP, VIP, CGRP, nNOS, Chat),
      neurotrophins (NGF, BDNF, NT-3) and their own receptors (TrKA, TrKB, TrKC, p75)
      in the seminiferous tubules of male rats treated by LND in the light of the
      literature on this topic.

PMID- 17548266
TI  - Differential expression of aquaporin 3 in Triturus italicus from larval to adult
      epidermal conversion.
AB  - By using immunohistochemical techniques applied to confocal microscopy, the
      presence of aquaporin 3 water channel in the epidermis of Triturus italicus
      (Amphibia, Urodela) has been shown. We analysed the expression of aquaporin 3
      (AQP3) during the larval, pre-metamorphic and adult phases; we also showed the
      localization of the water-channel protein AQP3 in free-swimming conditions and
      during aestivation in parallel with histological analysis of the skin, focusing
      on the possible relationship between protein expression and terrestrial habitats.
      Our results indicate that aquaporin is produced as the epidermis modifies during
      the functional maturation phase starting at the climax. Moreover, our data
      suggest an increase in enzyme expression in aestivating newts emphasizing the
      putative functional importance of differential expression related to a distinct
      phase of the biological cycle.

PMID- 17548267
TI  - Lung regions differently modulate bronchial branching development and
      extracellular matrix plays a role in regulating the development of chick embryo
      whole lung.
AB  - Normal branching development is dependent on the correlation between cells and
      extracellular matrix. In this interaction glycosaminoglycans, cytokines and
      growth factors play a fundamental role. In order to verify the distribution and
      influence of extracellular matrix and related enzymes on chick embryo lung
      development, 6 day-old whole lungs were maintained in vitro with testicular
      hyaluronidase, beta-N-acetyl-D-glucosaminidase and chondrotinase ABC or in
      linkage with apical, medial and caudal lung regions of 6-day development before
      and after enzyme treatment. In a separate lung region beta-N-acetyl-D
      glucosaminidase and hyaluronidase were determined. Our data show that the whole
      lung cultures increase bronchial branching development when the medial region is
      admixed separately, while the separate apical or caudal regions or apical
      combined with caudal region do not affect bronchial branching development. The
      enzyme treatment of medial region prevents the branching development in
      associated whole lung. The bronchial branching development of whole lung cultured
      in medium containing the enzymes related to glycosaminoglycans turnover is
      significantly altered. In conclusion, these data show that the different
      influence of separate apical, medial, caudal lung regions on bronchial branching
      development is related to the extracellular matrix composition.

PMID- 17548268
TI  - Expression of ATP sensitive K+ channel subunit Kir6.1 in rat kidney.
AB  - ATP-sensitive K+ (K(ATP)) channels in kidney are considered to play roles in
      regulating membrane potential during the change in intracellular ATP
      concentration. They are composed of channel subunits (Kir6.1, Kir6.2), which are
      members of the inwardly rectifying K+ channel family, and sulphonylurea receptors
      (SUR1, SUR2A and SUR2B), which belong to the ATP-binding cassette superfamily. In
      the present study, we have investigated the expression and localization of Kir6.1
      in rat kidney with Western blot analysis, immunohistochemistry, in situ
      hybridization histochemistry, and immunoelectron microscopy. Western blot
      analysis showed that Kir6.1 was expressed in the mitochondria and microsome
      fractions of rat kidney and very weakly in the membrane fractions.
      Immunohistochemistry revealed that Kir6.1 was widely distributed in renal tubular
      epithelial cells, glomerular mesangial cells, and smooth muscles of blood
      vessels. In immunoelectron microscopy, Kir6.1 is mainly localized in the
      mitochondria, endoplasmic reticulum (ER), and very weakly in cell membranes.
      Thus, Kir6.1 is contained in the kidney and may be a candidate of mitochondrial
      K(ATP) channels.

PMID- 17548269
TI  - Bismuth ions are metabolized into autometallographic traceable bismuth-sulphur
      quantum dots.
AB  - Bismuth - sulphur quantum dots can be silver enhanced by autometallography (AMG).
      In the present study, autometallographic silver enhanced bismuth-sulphur
      nanocrystals were isolated from unfixed cryo-sections of kidneys and livers of
      rats exposed to bismuth (Bi207) subnitrate. After being subjected to AMG all the
      organic material was removed by sonication and enzymatic digestion and the silver
      enhanced Bi-S quantum dots spun down by an ultracentrifuge and analyzed by
      scintillation. The analysis showed that the autometallographic technique traces
      approximately 94% of the total bismuth. This implies that the injected bismuth is
      ultimately captured in bismuth-sulphur quantum dots, i.e., that Bi-S nanocrystals
      are the end product of bismuth metabolism.

PMID- 17548270
TI  - An improved and cost-effective methodology for the reduction of autofluorescence
      in direct immunofluorescence studies on formalin-fixed paraffin-embedded tissues.
AB  - Interference by autofluorescence is one of the major shortcomes of
      immunofluorescence analysis by confocal laser scanning microscopy (CLSM). CLSM
      requires minimal tissue autofluorescence and reduced unspecific fluorescence
      background, requisites that become more critical when direct immunofluorescence
      studies are concerned. To control autofluorescence, different reagents and
      treatments can be used. Until now, the efficacy of the processes described
      depended on the tissue type and on the processing technique, no general recipe
      for the control of autofluorescence being available. Using paraffin sections of
      archival formalin-fixed murine liver, kidney and pancreas, we have found that
      previously described techniques were not able to reduce autofluorescence to
      levels that allowed direct immunofluorescence labelling. In this work, we aimed
      at improving currently described methodologies so that they would allow reduction
      of the autofluorescent background without affecting tissue integrity or direct
      immunofluorescence labelling. We have found that the combination of short
      duration, high-intensity UV irradiation and Sudan Black B was the best approach
      to reduce autofluorescence in highly vascularised, high lipofuscins' content
      tissues, such as murine liver and kidney, and poorly vascularised, low
      lipofuscins' content tissues such as the pancreas. In addition, we herein show
      that this methodology is highly effective in reducing autofluorescent background
      to levels that allow detection of specific signals by direct immunofluorescence.

PMID- 17548271
TI  - Do culturally sensitive services for Chinese in-patients make a difference?.
AB  - Hospitals in large cities provide services to an increasingly diverse linguistic
      and cultural clientele. Some strategies adopted to improve services to non
      English speaking populations include the use of bilingual social workers,
      interpreters and printed translation tools. In order to identify gaps in
      culturally sensitive care in a Canadian teaching hospital, this study surveyed a
      consecutive sample of 279 Chinese in-patients to determine satisfaction with
      hospital experience, levels of information about hospital routines and awareness
      of on-site Chinese cultural services. Results were generally positive. However,
      satisfaction and information levels were significantly higher among those
      patients who were aware of culturally appropriate Chinese resources such as
      social workers, cultural interpreters, and culturally specific reference tools.
      Of particular interest are the 121 patients (44%) who were less comfortable with
      English, since awareness of culturally specific resources tended to make a
      greater difference to this sub-group. These results can potentially help health
      care providers improve services to patients and families from diverse cultural
      and linguistic groups.

PMID- 17548272
TI  - Does difference matter? Diversity and human rights in a hospital workplace.
AB  - The urban hospital workplace is a dynamic environment that mirrors the cultural
      and social diversity of the modern city. This paper explores the literature
      relating to diversity in the workplace and then describes an urban Canadian
      teaching hospital's comprehensive approach to the promotion of an equitable and
      inclusive diverse environment. With this goal, four years ago the hospital
      established an office of Diversity and Human Rights staffed by a social worker.
      The office provides education, training, policy development and complaints
      management. The administration also convened a hospital-wide committee to advise
      on the outcomes, and to plan a process for diversity and human rights
      organizational change. The committee worked with a social work research
      consultant to design a qualitative focus group study, currently ongoing, to
      explore the perspectives of hospital staff. The lessons learned from the process
      have the potential to increase overall cultural competency of staff that can
      translate into more sensitive work with patients.

PMID- 17548273
TI  - Best practice case management for improved medical adherence.
AB  - Less than optimal treatment adherence for many health conditions impedes clinical
      progress, leading to increased morbidity, mortality and health care costs,
      particularly for low-income and racial and ethnic minority patients. When
      properly understood as a complex phenomenon involving patient, provider, and
      health system interacting factors, adherence improvement is a natural target for
      social work's multi-system model of case management. We present five key elements
      for a generic "best practice" case management blueprint applicable to a range of
      medical settings. The theory and evidence base for the elements are discussed and
      illustrated with SAFe, a tested social work case management program to improve
      adherence following abnormal cancer screens.

PMID- 17548274
TI  - Improvement of return rates in a Neonatal Hearing Screening Program: the
      contribution of social work.
AB  - This paper aims to describe the implementation of a Neonatal Hearing Screening
      Program in a school hospital, focusing on the return rates among infants who
      failed the first screening. The population who goes to the school hospital for
      health services comes mainly from economically underprivileged groups. Even
      though our previous return rates were comparable to those reported elsewhere, we
      felt it was important to improve the methodology of the screening process in
      order to try and obtain better results. Our hypothesis was that scarce knowledge
      on early hearing loss detection and on the benefits of early intervention could
      be reasons for mothers to give less importance to the second screening. So, a
      strategy was developed around the idea of providing very detailed information to
      the mothers about the screening process since preliminary data, gathered with a
      different group of in-patients, had shown that mothers possessed little knowledge
      about neonatal hearing screening and the consequences of hearing loss for
      children's development. The no-return rates decreased considerably (from 39.8% to
      25.8%). The findings of this research showed both the need of an adequate way of
      imparting information to the mothers of newborns about hearing screening in
      economically underprivileged populations, and the role of social work in this
      process. Without adequate knowledge on hearing screening and the consequences of
      hearing loss, a high percentage of newborns may not take advantage of free
      universal hearing screening programs.

PMID- 17548275
TI  - Physicians' ability to influence the life-style behaviors of diabetic patients:
      implications for social work.
AB  - Diabetes is aggravated by a sedentary lifestyle, obesity and smoking. Based on a
      theoretical model relating attitudes and behavior, this study examined the
      association between physicians' self efficacy in counseling diabetic patients on
      life style behaviors and their counseling practices. Data were gathered from a
      representative sample of 743 primary care physicians in Israel's two largest
      health plans. The main findings were that only a small percentage of physicians
      felt capable of influencing their patients' life-style behaviors. Self-efficacy
      had an independent effect on the likelihood of counseling diabetic patients on
      life style behaviors, controlling for other background variables. We conclude
      that there is a need for enhancing physicians' life-style counseling skills, and
      that social workers could expand their role by training physicians to counsel
      effectively. This could both improve the care of diabetic patients, and
      strengthen the status of the social work profession in the healthcare system.

PMID- 17548276
TI  - Perceptions of online support for hospitalized children and adolescents.
AB  - This study identifies perceived outcomes following hospitalized children's
      participation in a pediatric online support network. Nineteen participants were
      interviewed, including child and adolescent patients who had used the network
      while in hospital, their parent/family caregiver, and a familiar health care
      provider. This triadic sampling approach provided a range of stakeholder
      perceptions. Results convey a wide spectrum of benefits and challenges in
      accessing and utilizing an online support network for hospitalized children.
      Participation in the network was identified as a means of fostering pediatric
      patient enjoyment, education, connection with peers, and coping. Information,
      social connection and distraction served as catalysts fostering positive outcomes
      for children. Identified barriers to network participation included
      inaccessibility and limited availability of computers, issues with technology,
      and discomfort with online interaction. Findings advance understanding of online
      networks as supportive resources for seriously ill children and their families.

PMID- 17548277
TI  - Clinical practice standards and ethical issues applied to a virtual group
      intervention for spousal caregivers of people with Alzheimer's.
AB  - Advances in technology have improved access to health and social services by
      offering more abundant and convenient choices for clients. In particular, the use
      of technology for delivering services to older adults and their families offers
      new possibilities for service delivery, by reaching people who are often
      isolated, and have difficulty accessing traditional services. Despite the
      continued advances in technology development and its integration into healthcare
      delivery, health care practitioners need to consider how to adapt and uphold
      clinical practice standards and address ethical issues in an e-health
      environment. Given the gap in the literature with respect to discussing these
      issues, this paper illustrates relevant issues in the context of developing and
      evaluating an Internet-based intervention for spousal caregivers of persons with
      dementia. Based on a four year project, a psychotherapeutic group intervention
      was delivered via the Internet to three groups of spousal caregivers. This
      article identifies some of the key practice standards and ethical issues that
      arise when using computer technology to deliver a psychotherapeutic group
      intervention. The article will also provide examples of relevant issues related
      to maintaining practice standards and ethical procedures that need to be
      addressed during the application of a computer-based psychotherapeutic group
      intervention for spousal caregivers of people with dementia.

PMID- 17548278
TI  - An evaluation of dyadic peer support for caregiving parents of children with
      chronic lung disease requiring technology assistance.
AB  - This study evaluated a dyadic peer support pilot intervention for parents of
      technology-assisted children with chronic lung disease. These medically-fragile
      children, living at home in the primary care of their parents, require continuous
      or intermittent assistance from technological support such as home oxygen,
      respiratory or cardiac monitors and/or mechanical ventilators. The intervention
      consisted of matching parents with similar caregiving responsibilities, in order
      to reciprocally engage in parent-to-parent support. Results identified mixed
      outcomes based on quantitative and qualitative methods. Participants conveyed
      benefits and limitations of this modality of peer-based support. They generally
      favoured peer support as a clinical resource for caregiving parents as the
      intervention offered a valued opportunity for mutual sharing with another parent
      who could understand the unique realities particular to caring for a medically
      fragile child. Sharing daily experiences was reported to reduce isolation,
      increase knowledge, and provide an important sense of feeling understood.
      Challenges associated with peer support included scheduling difficulties and
      personality incompatibility. Recommendations for program development in clinical
      settings are described.

PMID- 17548279
TI  - Knowledge and social work in health care - the case of Finland.
AB  - Studies carried out in different countries have shown that there is a lack of a
      common and up-dated knowledge base in social work, and that social workers make
      use of research in their everyday practice only to a very limited extent. On the
      other hand it has been shown that social workers feel they need knowledge but not
      necessarily in the form it is produced by the researchers. This paper explores
      issues of knowledge and competence in health social work based on the results of
      a survey and a focus group interview conducted among social workers in Finland.
      According to the results, social workers in health care do feel they need new
      knowledge. Some significant differences were found in the way health social
      workers view the acquisition and maintenance of professional competence and in
      the way they seek knowledge, when compared to social workers working in the
      municipal social services.

PMID- 17548281
TI  - The co-occurrence of depression and alcohol dependence symptoms in a community
      sample of lesbians.
AB  - Numerous studies have found an association between depression and alcohol use
      disorders in women. Little is known, however, about the relationship between
      depression and alcohol use among lesbians. We examined the prevalence of
      depression and alcohol dependence symptoms as well as the co-occurrence of these
      two health problems in a large community-based sample of women who self
      identified as lesbian. Past year alcohol dependence symptoms were significantly
      associated with both past year and lifetime depression. Lifetime depression was
      higher among White and Latina lesbians than among African American lesbians.
      Younger women and those not currently in a committed relationship more commonly
      reported past year depression. Younger age was the strongest predictor of the co
      occurrence of depression and alcohol dependence symptoms.

PMID- 17548282
TI  - Alcohol consumption, alcohol-related problems, and other substance use among
      lesbian and bisexual women.
AB  - Relationships between sexual orientation and a wide range of substance use and
      problem variables were examined based on data from the 2000 National Alcohol
      Survey. Lesbians, bisexuals, and heterosexually identified women who report same
      sex partners were compared to exclusively heterosexual women in relation to
      alcohol consumption, use of tobacco and other drugs, bar-going, alcohol-related
      problems, and past substance abuse treatment. Substance use patterns were complex
      and varied between sexual orientation groups. These differences underscore the
      importance of developing lesbian- and bisexual-sensitive prevention and treatment
      services and of including measures of sexual orientation identity and behavior in
      population-based surveys.

PMID- 17548283
TI  - Alcohol use and alcohol-related problems in self-identified lesbians: age and
      racial/ethnic comparisons.
AB  - Age cohort and racial/ethnic differences in alcohol-use patterns and alcohol
      related problems were examined in a diverse sample of self-identified lesbians
      using data from the Chicago Health and Life Experiences of Women Study (CHLEW).
      Significant differences in lifetime drinking patterns and lifetime alcohol
      related problems were found across three generational cohorts; few differences
      were found across racial/ethnic groups. Findings are discussed in relation to
      previous research on lesbian alcohol use.

PMID- 17548284
TI  - Substance use and social identity in the lesbian community.
AB  - Although the study results report discrepancies in the rates of substance abuse
      in the lesbian community, the general consensus in the field of gay and lesbian
      studies is that these individuals, as a whole, have a higher rate of substance
      use. For this study, data were collected via the Internet on the use of drugs and
      alcohol, level of self-esteem, and degree of social identity in the lesbian
      community. A correlation analysis was used to determine if negative social
      identity within the lesbian community leads to low self-esteem that is reflected
      in higher rates of substance abuse. Though a positive relationship between social
      identity and self-esteem was determined, no significant correlation between
      negative social identity, low self-esteem, and substance use was determined.
      However, it is important to consider that respondents with higher levels of self
      esteem reported more frequent use of specific drugs. That outcome in itself is an
      implication for further investigation.

PMID- 17548285
TI  - Toward a grounded theory of lesbians' recovery from addiction.
AB  - This article presents the results of a qualitative study on lesbians' recovery
      from addiction. The study involved semi-structured interviews with 20 lesbians in
      recovery from addiction and was analyzed using grounded theory method. The
      central theme that emerged was self-acceptance, both as a lesbian and as a
      recovering alcoholic/addict, with considerable interaction between the two.
      Categories that contributed to this theme were learning to recover, relationships
      with other people, and relationship with something bigger than self. The
      discussion addresses how this information can be used to assist lesbians trying
      to recover from addiction.

PMID- 17548286
TI  - Labelling out: the personal account of an ex-alcoholic lesbian feminist.
AB  - In this paper, I look at my past alcohol dependency from a political as well as
      personal perspective. I consider the problems caused in my life and that of other
      lesbians by alcohol abuse, outdated treatment methods and self-help organizations
      such as AA, which misrepresent social factors leading to alcohol abuse. I focus
      on a series of themes: the personal and political; lesbian bar styles;
      alternative realities; lesbian problem drinking; problems facing lesbians in
      treatment and engaging with Alcoholics Anonymous; treatment as it often is and
      treatment as it should be.

PMID- 17548287
TI  - Lesbian, gay, and bisexual clients' experiences in treatment for addiction.
AB  - This study examined the extent to which lesbian, gay, and bisexual clients
      perceived their addiction counselors and treatment programs to be sensitive to
      issues related to sexual orientation. The experiences they considered most
      successful were reported as more affirmative than experiences they considered
      least successful; however, in neither situation were counselors or treatment
      programs consistently affirmative.

PMID- 17548288
TI  - Predicting, understanding and changing: three research paradigms regarding
      alcohol use among lesbians.
AB  - The author presents a paradigmatic categorization and review of the literature
      that is available regarding lesbians and alcohol. She illuminates the
      characteristics, shortcomings, and strengths of Empirical Post Positivist,
      Interpretive, and Critical Social research paradigms. Results of the various
      studies are presented while research and funding directions are proposed.

PMID- 17548289
TI  - Exploring an HIV paradox: an ethnography of sexual minority women injectors.
AB  - HIV risk and infection are markedly increased among sexual minority women
      injectors compared to other injecting drug users. Our ethnographic exploration of
      this well-documented but poorly understood phenomenon included 270 interviews and
      over 350 field observations with 65 sexual minority women injectors in New York
      City and Boston. We discuss findings in relation to four preliminary hypotheses.
      Neither the presence of gay or bisexual men in risk networks, nor a sense of
      invulnerability due to lesbian (or other sexual minority) identity seem to be
      plausible explanations of increased HIV among sexual minority women injectors.
      However, multiple marginalization was found to be pervasive and to have severe
      consequences that can be traced to increased HIV risk for many women in the
      study.

PMID- 17548290
TI  - When mothers learn a daughter is a lesbian: then and now.
AB  - This manuscript is based on in-depth interviews of 3 groups of mothers who
      learned that their daughters were lesbian. The first group consisted of 10
      mothers interviewed in 1990. A second group of 16 mothers were interviewed in
      2000-2001. The third group, also interviewed in 2000-2001, consisted of 14
      mothers whose daughters initially disclosed as lesbians, but later identified as
      transgender. Conducted 10 to 11 years apart, these studies offer a comparison of
      the initial reactions of mothers prior to and following a time of marked changes
      in attitudes towards homosexuality. Findings demonstrated that while the majority
      of mothers interviewed in 1990 experienced disclosure as a crisis, a greater
      number of mothers in 2000-2001 were more receptive to learning that a daughter
      was a lesbian.

PMID- 17548291
TI  - Introduction: lesbian academic couples.

PMID- 17548292
TI  - A stitch in time: an experiment in collaboration.
AB  - Writing biography is rarely as straightforward as simply drawing together the
      threads of someone else's life. Not only must the biographer grapple with the
      challenge of pulling that life into a narrative shape, she must also deal with
      the issue of the biographical self to consider the way in which that self impacts
      and influences the story. Seen like this, biography becomes a collaborative
      experience--a mesh of self/other relations. Using the case study of the "Michael
      Fields "--the subjects of my biography in-progress--this paper explores the
      effects of the researcher/subject relationship and the way in which it affects a
      kind of scholarly desire both on (and off) the page.

PMID- 17548293
TI  - Becoming the professors of lesbian love.
AB  - We tell here our all-too-unusual story of living and working together, reflecting
      on both the obstacles and the forces that made it possible for us to find each
      other, stay together, and develop a collaborative working relationship. Despite
      experiencing various forms of discrimination, we have been able over the years to
      contribute to the creation of a queer community through hiring lesbian
      colleagues, attracting lesbian and gay students, participating in the lesbian,
      gay, bisexual, and transgender movement, and advocating social justice for women
      and gay, lesbian, bisexual, and transgender people in our respective professional
      associations. This is the story of becoming the "professors of lesbian love," a
      title bestowed upon us by the drag queens we studied in our most recent joint
      project.

PMID- 17548294
TI  - We're both tenured professors . . .but where is home?
AB  - Mills' sociological imagination is used to look at relevant issues in the life of
      a lesbian academic couple in a distance relationship. Analysis includes concerns
      which are common to both lesbian and heterosexual couples in distance situations
      such as finding jobs, tenure, productivity, mentoring, managing two households,
      communication, community, and those items unique to lesbian couples-coming out to
      students, finding and maintaining a lesbian community, effects of hiring
      practices in academe. Based on the analysis, recommendations are presented.

PMID- 17548295
TI  - "Course is team taught": dimensions of difference in classroom pedagogy.
AB  - We report on students' response to kinds of difference in the classroom as we
      have assessed it in our personal experience as a same-sex, mixed race, leftist
      couple team teaching in two disciplines and at five separate schools over a
      number of years. We argue that students are more accepting of differences arising
      out of sexual preference and race and most resistant to differences arising out
      of class, especially poverty.

PMID- 17548296
TI  - Dual-career queer couple hiring in southwest Virginia: or, the contract that was
      not one.
AB  - Although dual-career hires are a common recruitment tool in academe, they remain
      a challenge for institutions hiring same-sex couples. This narrative tells the
      story of one such couple--it focuses on our professional and personal journey and
      the collective social activism that challenged one university to begin to address
      issues that face LGBT faculty throughout higher education.

PMID- 17548297
TI  - Unruly democracy and the privileges of public intimacy: (same) sex spousal hiring
      in academia.
AB  - Within the context of a discussion of lesbian academic couples there is something
      to be said about the (dis)pleasures and profits of a heteronormative practice
      such as spousal hiring and how much this privilege reveals the broader systemic
      discrimination vis-a-vis sexual and gender claims in our academic institutions.
      Two issues emerge from its (questionable) application: (1) How a privilege such
      as spousal hiring intersects with institutional policies concerning sexual
      diversity; and in light of this, (2)Why queer or lesbian couples shouldn't
      embrace dubious spousal hiring incentives.

PMID- 17548298
TI  - Performing transformation: reflections of a lesbian academic couple.
AB  - We experience queer literacy as a kind of collision between the traditional and
      the transformative. Queer literacy is an acquired literacy of transformation,
      where the established rules of behavior and discourse are both challenged and
      transcended. As a lesbian academic couple in a privileged intellectual,
      political, and social location, we can move out of the traditional realm (through
      the closet) into an otherworldly queer space where knowledge and identity are
      destabilized. Moving in and out of queer transformative space requires a kind of
      blind faith-faith that believes in what the mind can neither see nor prove.

PMID- 17548299
TI  - [The roles of histone lysine methylation in epigenetic regulation].
AB  - Histone lysine methylation plays a key role in epigenetic regulation.There are
      five lysines within histone H3(K4, K9, K27, K36, K79). Besides, one lysine within
      histone H4(K20) has been shown to be methylated by specific histone lysine
      methyltransferase. Methylation at H3-K9 is associated with transcriptional
      repression, while methylation at H3-K4 and H3-K36 is associated with
      transcriptional activation. The methylation of histone H3-K27 was proved to be
      linked to several silencing phenomena including homeotic-gene silencing, X
      inactivation and genomic imprinting. H3-K79 methylation plays a role in DNA
      repair and transcriptional activation, and the extent and biological significance
      of histone de-methylation will surely attract great attention.

PMID- 17548300
TI  - [Single nucleotide polymorphisms and fine mapping QTL in chickens].
AB  - As an important economically animal and a model animal, a great of progress of
      SNP diversity and QTL mapping in chickens have been made in recent years. The
      present paper not only summarized these achievements but also commanded an
      extensive view about the fine mapping of QTL by the use of SNP marker.

PMID- 17548301
TI  - [Progress in rice genes mapping and gene distribution in chromosomes].
AB  - Mapping a target gene is useful to isolate the gene or get molecular marker for
      molecular marker-assisted selection. This paper summarized the recent studies of
      gene mapping in rice, including 194 genes. These genes are involved in disease
      resistance, cold tolerance, drought resistance, sterility, and fertility
      restoration of rice. The molecular markers that link with these genes were also
      summarized. Among these genes 14 have been cloned and sequenced. According to the
      results this paper also analyzed genes distribution rule in chromosomes.

PMID- 17548302
TI  - [The mechanism of root hair development and molecular regulation in plants].
AB  - The formation of the root epidermis in Arabidopsis thaliana provides a simple
      model to study mechanisms underlying patterning in plants. Root hair increases
      the root surface area and effectively increases the root diameter, so root hair
      is thought to aid plants in nutrient uptake, anchorage and microbe interactions.
      The determination of root hair development has two types, lateral inhibition with
      feedback and position-dependent pattern of cell differentiation. The initiation
      and development of root hair in Arabidopsis provide a simple and efficacious
      model for the study of cell fate determination in plants. Molecular genetic
      studies identify a suite of putative transcription factors which regulate the
      epidermal cell pattern. The homeodomain protein GLABRA2 (GL2), R2R3 MYB-type
      transcription factor WEREWOLF (WER) and WD-repeat protein TRANSPARENTT TESTA
      GLABRA (TTG) are required for specification of non-hair cell type. The CAPRICE
      (CPC) and TRYPTICHON (TRY) are involved in specifying the hair cell fate.

PMID- 17548303
TI  - [The analysis method and progress in the study of codon bias].
AB  - Codon bias refers to the nonrandom usage of synonymous codons for encoding amino
      acids in organisms. As it is related to the carrier molecular of genetic
      information (DNA) and functional molecular (protein) of life, this phenomenon
      implicates important biological sense. In this review, we summarize the basic
      theories and analysis methods about codon bias; and present the softwares and
      websites which are usually used for codon usage analysis. The related fields
      about codon bias and the research progress are also introduced.

PMID- 17548304
TI  - [Analysis of association between COL9A1 gene and idiopathic congenital talipes
      equinovarus].
AB  - Genotypes of 2 SNPs(rs592121 and rs1135056) within COL9A1 gene in 84 ICTEV
      nuclear pedigrees were analyzed by restriction fragment length polymorphism and
      DNA sequencing. Analysis of association between SNP locus and ICTEV was performed
      using ETDT software. Haplotypes and their frequencies in 84 nuclear pedigrees
      were established and analyzed by TRANSMIT software. RT-PCR was used to detect the
      expressions of COL9A1 mRNA in 25 patients with ICTEV. The results showed that
      rs592121 and rs1135056 loci within COL9A1 gene existed transmission
      disequilibrium in 84 nuclear pedigrees (P<0.05). Expression of COL9A1 on mRNA
      levels showed significantly higher in patients with ICTEV than in normal person
      (t=4.7500, P<0.05) . These results indicate that COL9A1 gene may be important
      suscept-ble genes of ICTEV.

PMID- 17548305
TI  - [Study on a new point mutation of nt7444 G-->A in the mitochondrial DNA in a type
      2 diabetes mellitus family].
AB  - Polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) and
      direct sequencing were applied to detect a new point mutation of nt7444G-->A in
      the mitochondrial DNA in a type 2 diabetes mellitus family. The related clinical
      data were also collected and analyzed. mtDNA G7444A mutation in the cytochrome c
      oxidase I (COI) gene was found in 11 of 27 cases, all of whom were from the
      maternal side. Among them, 5 were confirmed to have type 2 diabetes mellitus, and
      one had impaired glucose tolerance. We conclude that the novel point mutation of
      mtDNA G7444A may be an independent factor associated with type 2 diabetes
      mellitus.

PMID- 17548306
TI  - [Polymorphic analysis of intron 2 and 3 of growth hormone gene in duck].
AB  - The single nucleotide polymorphism (SNP) of growth hormone gene was investigated
      in various breeds of duck, including Beijing ducks, Xihu mallards, Jinding ducks,
      Shan Partridge ducks, Jingjiang ducks and Shaoxing ducks. The primers for intron
      2 and 3 in GH gene were designed based on the database of duck genomic sequence
      and the SNPs were detected by PCR-SSCP method. Eight SNPs were found among
      individuals within a breed, which were 2593(C-T), 2770(G-A), 2813(T-A), 2829(C
      A), 2894(C-T), 2896(T-C), and 3100(C-G) in intron 2 and 3270(A-G) in intron 3.
      The analytic results showed that the frequencies of genotypes in different breeds
      were significantly different. Based on these SNPs, Beijing ducks and Shaoxing
      ducks represented their own unique conservativeness, indicating that these SNPs
      may have relationship with some productive traits of duck.

PMID- 17548307
TI  - [AFLP analysis in populations of Strongylocentrotus intermedius, S. nudus and
      hybrids (S. intermedius x S. nudus)].
AB  - AFLP analysis of genetic diversity in the three populations of sea urchin
      Strongylocentrotus intermedius (IN), S. nudus (NU) and F1 progeny (INxNU) was
      carried out in this paper. In total, 272 loci were amplified with 4 primer pairs,
      of which 269 were polymorphic and the percentage of polymorphic loci was 98.89%.
      The Shannon diversity index for S. intermedius, S. nudus, and their hybrid
      populations was 0.2331+/-0.1273, 0.2005+/-0.1385, and 0.2625+/-0.1067,
      respectively. The genetic similarity within populations was 0.6876+/-0.0523,
      0.6501+/-0.0548, and 0.6552+/-0.0553, respectively. AMOVA analysis indicated that
      25.39% of variance was among populations and 74.61% of variance was within
      populations. This suggested the rich genetic diversity level within populations.
      Although the hybrids can be classified into two types by apparent characters,
      they were clustered each other by UPGMA method according to their genetic
      distances.

PMID- 17548308
TI  - [FISH analysis of 45S rDNA and 5S rDNA genes in Triticum polonicum L. and T.
      turgidum L. cv. Ailanmai].
AB  - Using the method of double color fluorescence in situ hybridization (FISH), we
      had analyzed Triticum polonicum L. and T. turgidum L. cv. Ailanmai with the
      probes of 45S rDNA and 5S rDNA. The results indicated that there were highly
      consistent in T. polonicum L. High and T. turgidum L. cv. Ailanmai, both having
      four 45S rDNA loci and six 5S rDNA loci. In T. polonicum L. Dwarf, there were
      also four 45S rDNA loci, the same as that in T. polonicum L. High and T. turgidum
      L. cv. Ailanmai, but there were eight 5S rDNA loci. At the same time, we
      discussed the reason of interspecific and intraspecific variation of the two
      types of rDNA in locus number and location between T. polonicum L. and T.
      turgidum L. cv. Ailanmai.

PMID- 17548309
TI  - [Distribution and SNPs of the rice CMS-related gene in AA-genome of Oryza
      species].
AB  - The moiety of a chimeric gene in mitochondrial genome, orf79 and orfH79, probably
      related to BT-type and HL-type CMS of rice respectively, has 98% homology and
      only 4 nucleotide variation in DNA sequence. Of which, the former comes from
      Oryza sativa L., and the latter originates from Oryza rufipogon Griff. That means
      the orf79/ orfH79 may widely exist in Oryza species with AA genome. In order to
      investigate the distribution and difference of orf79/ orfH79 in the Oryza
      species, 190 cultivated rice accessions (including O. sativa and O. glaberrima)
      and 104 accessions of AA-genome Oryza wild species (including O. nivara, O.
      rufipogon, O. barthii, O. longistaminlata, O. glumaepatula, and O. meridion-alis)
      were detected with PCR amplification. Of which, 31 accessions mainly from AA
      genome Oryza species were found to share the special amplified fragment with the
      control of Yuetai A and Shijin A. The special amplified fragments were all
      recovered and sequenced. Phylogenetic analysis based on DNA sequences showed that
      the 31 accessions were fallen into two groups, correspondingly representing HL
      type and BT-type cytoplasm group. Further, the results revealed that the HL-type
      cytoplasm distributed mainly in annual O. nivara, and the BT-type cytoplasm
      centered in cultivated varieties or perennial O. rufipogon.

PMID- 17548310
TI  - [Cytogenetical comparison of restorers TP-4 and D minghui63 and maintainer D46B
      of autotetraploid rice].
AB  - Cytogenetical comparison was made between high seed set restorers TP-4 and D
      minghui63 and eminent maintainer line D46B of autotetraploid rice. The meiosis
      observation demonstrated the genomes of our autotetraploid materials were all 2n
      = 48, the same as those in mitosis observation. Low percentages of univalent and
      trivalent in metaphase I (MI) of restorers TP-4 and D minghui63 and in metaphase
      I (MI) of maintainer line D46B of autotetraploid rice were observed. And the
      percentages of chromosome pairing were all over 99%, showing eminent cytological
      character. The frequency of TP-4 and D minghui63 in metaphase I (MI) was 2.00/PMC
      and 2.26/PMC, respectively. However the frequency of D46B was 6.00/PMC,
      significantly higher than those of TP-4 and D minghui63. It indicated that the
      maintainer D46B has better chromosome pairing capability in metaphase I (MI).
      While, the frequency of lagging chromosomes of the maintainer D46B in anaphase I
      (AI) was 10.62%, significantly lower than that of TP-4 (19.44%) or D minghui63
      (23.14%), and it was close to the level of diploid control (7.30%). In telophase
      I (TI), maintainer D46B exhibited a lower frequency of microkernel, and in
      telophase II (TII) the frequency of normal quartered microspore of maintainer
      D46B was not only higher than that of TP-4 or D minghui63 but also than that of
      diploid control. The percentage of the cell observed chromosome lagging in A1 and
      the percentage of abnormal cell in TI showed a greatly significant positive
      correlation. That may demonstrate chromo some separation in anaphase I (AI) and
      microkernel formation in telophase I (TI) are controlled by the same dominant
      single gene or the major gene of QTL.

PMID- 17548311
TI  - [The inheritance of an ultra-dwarf plant mutant from upland cotton].
AB  - The inheritance of an ultra-dwarf plant mutant from upland cotton (Gossypium
      hirsutum L.) was studied, which showed that the mutant was controlled by single
      recessive quality gene. This gene was denominated as du tentatively. No similar
      mutant has been found in upland cotton. The mutation could not normally flower
      and produce bolls under natural conditions, and its mature height was only 10.5
      cm. When treated with exogenous GA3, it could normally flower and boll, and plant
      height could reach 57.8 cm finally.

PMID- 17548312
TI  - [The screening of mutants induced by physical and chemical factors and
      construction of mutant population for Brassica napus L].
AB  - The mature seeds of rapeseed (Brassica napus L.) from variety Gaoyou 605 were
      treated with g-rays and Ethyl Methan Sulfonate (EMS). 152 mutants (12.67% of M2
      population) with mutative traits, including the mutation of leaf color, leaf
      shape, plant height, number and angle of branches, diameter of main stalk, color
      of stalk and flower, number and size of petals, pistil shape, male sterility, bud
      death and date of bloom were found in screened M2 progenies, which have been
      identified in M3. The mutants of cotyledon and root traits were also screened by
      hydroponics culture and their total mutant frequency were estimated at 12.78% and
      7.07% in M3, respectively. Identification of M4 showed that these mutations could
      be inherited stably. The mutant library including the mutants of leaf, plant
      type, flower, cotyledon, root and physiological traits had been built in present
      experiment. These mutants might be used as important germplasm for rapeseed
      breeding and functional genomics study.

PMID- 17548313
TI  - [Identification and analysis of differentially expressed genes during wood
      formation in Chinese fir by SSH].
AB  - Wood is an important raw material for the global industry with rapidly increasing
      demand. To isolate the differentially expressed genes in xylogenesis of Chinese
      fir [Cunninghamia lanceolata (Lamb.) Hook], a forward subtractive cDNA library
      was constructed using suppression subtractive hybridization (SSH) method, which
      was performed using the cDNA from the mutant Dugansha clone as the tester and the
      cDNA from the normal Jurong 0 clone as the driver. Six hundred and eighteen
      clones were obtained. Recombinants were identified using PCR with universal T7
      and SP6 primers and using EcoR digestion. To further eliminate false positive,
      dot hybridization was used with four DIG-labeled probes (FSP, RSP, UTP, and UDP).
      Real-time PCR was performed to confirm the results. A total of 260 unique ESTs
      were obtained, 60% of the ESTs exhibiting homologies with proteins of known
      function fell into 4 major classes: metabolism, cell wall biogenesis and
      remodeling, signal transduction and stress. The systematic analysis of genes
      involved in wood formation in Chinese fir provides valuable insights into the
      molecular mechanisms involved in xylem differentiation, is important resources
      for forest research directed toward understanding the genetic control of wood
      formation and future endeavors to modify wood and fiber properties for industrial
      use.

PMID- 17548314
TI  - [The analysis of differential expression and cloning of genes related to raised
      secondary lateral veins mutant of Lycoris aurea].
AB  - Lycoris aurea exhibits parallel venation, the main vein with many lateral veins
      in a longitudinal parallel arrangement. There are secondary lateral veins (SLV)
      between each longitudinal veins. In general, SLVs are not remarkable. In this
      paper, the material was one kind of Lycoris aurea mutant called Raised Secondary
      Lateral Veins mutant (RSLV), because many Raised Secondary Lateral Veins are in
      abaxial surface of its leaves. Its growing potential is weaker than that of wild
      type and its blades are very thin. Moreover, the stamens of RSLV degenerate
      completely. Two cDNA libraries were constructed from RSLV mutant and wild type
      (WT) leaves. From the libraries, 3,122 ESTs, which are longer than 100 bp each
      after vector sequence removed, were acquired by single-pass sequencing from the
      5'end. Following a multistep selection, 512 70-mer oligo-DNA probes were designed
      for attachment on the microarray slide based on the ESTs. The gene expression
      profile of RSLV mutant and WT leaves was compared through the microarray at
      transcriptional level. The microarray experiment results were further confirmed
      by Quantitative Real-Time PCR (QRT-PCR). We identified 5 genes whose expressions
      changed more than 2-fold between RSLV mutant and WT leaves. They encode phloem
      protein 2 (PP2), ferritin, pectin methyl esterase (PME), chlorophyll a/b binding
      protein (CAB protein) and pyruvate decarboxylase (PDC), respectively.
      Furthermore, the full-length cDNA sequences of the 5 genes were separately
      obtained from RSLV and WT by RACE. The relationship between differential
      expressions of the genes and the formation of the RSLV mutant phenotype were
      discussed.

PMID- 17548315
TI  - [Quick testing-technology of transgenic rice with npt- screen marker gene].
AB  - By using npt-gene as assistant selection-marker, treating Japonica rice Zhonghua
      9 [ZH9 (CK)] and transferred lysozyme gene rice (the donor rice is Japonica rice
      Zhonghua 9) [ZH9(R)] with antibiotics, we built a system of quickly testing
      transgenic rice offspring. Detached leaves of ZH9(R) and ZH9(CK) were treated by
      Kanamycin (0, 400, 450, 500, 550, 600 and 700 mg/L) and G418 (0, 40, 60, 80, 100,
      150 and 200 mg/L) with different concentrations. The result show effect of
      Kanamycin is not evident and G418 is the best antibiotics to test transgenic rice
      with npt- gene. The data showed that 80 mg/L G418 (treating 4 d) was optimal to
      test transgenic rice. Further study was done with seeds, young embryos and
      seedlings by G418 testing: the alive seeds were cultured in the culture dishes
      which filled with a series of G418 solution with different concentration of 0,
      100, 150, 200, 250, 300 and 350 mg/L; in the tissue culture room, the germinating
      embryos were inoculated in the culture medium (1/2 MS+0.5 mg/L 6-BA+1.5% sucrose)
      which contains G418 with 0, 150, 200, 250 and 300 mg/L concentration; the aseptic
      seedlings were inoculated in the the same culture medium (1/2 MS+0.5 mg/L 6
      BA+1.5% sucrose) which contains G418 with 0, 100, 150, 200 and 250 mg/L
      concentration. The conclusions indicated that 300 mg/L (treating 7 d) was the
      critical concentration to test seeds of transgenic rice; 200 mg/L (treating 10 d)
      was the critical concentration to test young embryo of transgenic rice; 150 mg/L
      (treating 12 d) was the critical concentration to test seedlings of transgenic
      rice. Two primers were designed based on npt- and lysozyme gene sequences. PCR
      technology confirmed the above detection system. The preliminary results showed
      npt-was tightly linked with lysozyme gene. Above confirmed critical
      concentrations were applied to test detached leaves, seeds, young embryos and
      seedlings of transferred generations. The effect was very obvious. It is
      convenient, intuitionistic, and exact way that aparting the positive plants from
      the mixture of transgenic positive and negative plants with G418.

PMID- 17548316
TI  - [Genomics innovative teaching pattern based upon amalgamation between modern
      educational technology and constructivism studying theory].
AB  - In order to overcome various malpractices in the traditional teaching methods,
      and also as part of the Guangdong province molecular biology perfect course
      project, some reforms were carried out to the teaching pattern of genomics. The
      reforms include using the foreign original teaching materials, bilingual
      teaching, as well as taking the constructivism-directed discussion teaching
      method and the multimedia computer-assisted instruction. To improve the scoring
      way and the laboratory course of the subject, we carried on a multiplex
      inspection systems and a self-designing experiments. Through the teaching reform
      on Genomics, we have gradually consummated the construction of molecular biology
      curriculum system.

PMID- 17548317
TI  - [BTEB/KLF9 and its transcriptional regulation].
AB  - BTEB/KLF9(basic transcription element-binding protein/Kruppel-like transcription
      factor 9), a member of Kruppel-like transcriptional factors, is a zinc finger
      protein involved in regulating gene transcription in eukaryocyte. Substantial
      expression of BTEB mRNA is detected in a variety of cell lines and tissues, but
      BTEB protein is not consistent with its mRNA. BTEB regulates transcription
      through its carboxyl-terminal C2H2 zinc finger motif binding to GC or GT/CACC
      box, a sort of cis-acting elements, which is wildly distributed in promoters,
      enhancers and control regions of many genes. BTEB/KLF9 functions as a
      transcription factor by direct or functional interaction with other transcription
      factors and/or coactivators/corepressors, and plays a role in reproductive
      system, cell proliferation, differentiation, and cell cycle regula-tion.

PMID- 17548318
TI  - [Research progress on nonsyndromic X-linked mental retardation related gene
      PAK3].
AB  - Mutations of the gene coding for PAK3 (p21-activated kinase 3) are associated
      with nonsyndromic X-linked mental retardation (MRX). It may be associated with
      generalized or specific cognitive ability. Studying the biological and cognitive
      function of PAK3 is important for MR diagnosis and prevention. This paper reviews
      the progress on PAK3 including its gene product, biological and cognitive
      function. The future directions on the study of PAK3 are also discussed.

PMID- 17548319
TI  - [Review on molecular regulation of in vitro shoot regeneration of plants].
AB  - In vitro shoot regeneration is a developmental process that multiple genes and
      their interactions are involved in. Initiation of somatic cells stimulated by
      cytokinin, division of the initiated somatic cells and succeeding shoot meristem
      development are three key steps in the process. Therefore, exploration of gene
      expression and their interactions involved in these steps will shed light on our
      understanding of the molecular mechanism for regulation of plant in vitro shoot
      regeneration. Here we reviewed the research results of molecular regulation
      process involved in these steps.

PMID- 17548320
TI  - [Effect of B-RAF-specific RNA interference on gastric cancer BGC823 cell line].
AB  - To investigate the influence of B-RAF-specific RNA interference on the
      proliferation and apoptosis of gastric cancer BGC823 cell line. B-RAF-siRNA and
      scramble-siRNA were synthesized and transfected into BGC823 cells by
      TransMessenger. The expression of B-RAF gene and Bcl-2 gene in BGC823 cells was
      detected by RT-PCR and the level of apoptosis was evaluated in transfected cells
      by flow cytometry. Results showed that TransMessenger could effectively transfect
      B-RAF-siRNA and scramble-siRNA into BGC823 cells. B-RAF-siRNA significantly
      inhibited the expression of B-RAF gene and Bcl-2 gene in BGC823 cells by more
      than 90% to 100%. B-RAF-siRNA inhibited BGC823 cell prolifera-tion and induced
      apoptosis (P < 0.01). In conclusion, B-RAF-siRNA can effectively inhibit the
      expression of B-RAF gene and Bcl-2 gene, induce cell apoptosis and inhibit the
      proliferation of gastric cancer BGC823 cells.

PMID- 17548321
TI  - [Association of apolipoprotein A5 gene -1131T/C polymorphism with lipid
      metabolism and insulin resistance in patients with type II diabetes mellitus].
AB  - The purpose of this study was to explore the frequency of apolipoprotein A5
      (APOA5) -1131T/C polymorphism in Zhenjiang and its effects on lipid metabolism
      and insulin resistance in type II diabetes mellitus(DM) patients. The genotypes
      of APOA5 -1131T/C polymorphism were determined in 152 healthy individuals and 71
      type II DM patients by polymerase chain reaction-restriction fragment length
      polymorphism (PCR-RFLP). Serum levels of lipids, glucose and insulin in these
      subjects were also estimated by biochemical methods. The frequency of the APOA5
      1131C allele in DM patients was significantly higher than that of the control
      group (0.430 vs 0.296, P = 0.006). When compared with the TT genotype, CC
      homozygotes had a significantly increased DM risk (OR=3.75, 95% CI: 1.57-8.92).
      In the DM group, the serum levels of triglyceride (TG) of C carriers (TC+CC) were
      significantly higher than those of non-C carriers (TT) (P 0.01), and serum levels
      of total cholesterol (TC) and low density lipoprotein cholesterol(LDL-c) in
      subjects with the CC genotype were also significantly higher than those with the
      TT genotype (P 0.05). However, there was no significance in profiles of insulin
      resistance in various genotypes in both groups. The APOA5 single nucleotide
      polymorphism was associ-ated with serum TG level in the population. The -1131C
      allele contributed to the increase of serum levels of TG, TC and LDL-c and but
      had no effect on profiles of insulin resistance in DM patients. The APOA5 -1131C
      allele may be associated with increased susceptibility to type II diabetes
      mellitus.

PMID- 17548322
TI  - [Epidermal growth factor receptor mutation in non-small cell lung cancer and
      breast cancer].
AB  - Somatic mutation in the tyrosine kinase (TK) domain of the epidermal growth
      factor receptor (EGFR) gene is associated with the sensitivity of non-smal cell
      lung cancer (NSCLC) to TK inhibitor Gefitinib. Mutational analysis for EGFR exons
      19 and 21 was performed in 75 NSCLC and 10 breast cancer patients. All patients
      had not received treatment of Gefitinib. Somatic mutations in TK domain of EGFR
      were identified in 13 of the 75(13/75, 17.33%) patients, including 7 cases of in
      frame deletion in exon 19 (7/75, 9.33%) and 6 cases of amino acid substitution
      (2573T>G, L858R) in exon 21 (6/75, 8%) . No other mutations were found in 10
      breast cancer patients who stained positive for HER2 immunhistochemistry.
      Adenocarcinoma has a higher rate of mutations than several other types of NSCLC,
      the mutations occurring more fre-quently in female patients. EGFR mutation rate
      in Chinese NSCLC patients was higher than that in Caucasians. Our data indicated
      that Chinese adenocarcinoma patients could benefit from TK inhibitor Gefitinib.

PMID- 17548323
TI  - [Analysis of apolipoprotein A5 gene polymorphisms in Hubei Han people].
AB  - Polymerase chain reaction-restriction fragments length polymorphism (PCR-RFLP)
      was used to explore the distribution of apolipoprotein A5 gene -1131T>C and 56C>G
      polymorphisms in 257 healthy Hubei Han people. The following results were
      calculated: the frequency of -1131TT genotype was 50.9%, far more than that of 
      1131TC and -1131CC genotypes (32.9% and 16.2%, respectively). The number of T
      allele carriers was higher than that of C carriers, and their respective
      frequencies were 0.675 and 0.325. There were 56GG and 56GC genotypes, but only 2
      individuals in all subjects carried the G allele, the frequency of which was low
      than 5%. Furthermore, the frequency of genotypes and alleles in apoa5 -1131T>C
      and 56C>G polymorphisms was clearly different from other races and areas. We
      conclude that the apoa5 -1131T>C variation should be considered a single
      nucleotide polymorphism, but the 56C>G variation should be considered as a
      mutation instead.

PMID- 17548324
TI  - [Molecular evolution of GAGE gene family].
AB  - The gene family GAGE is characterized to be expressed in testis and a portion of
      tumors, which is considered to be a candidate for diagnostic marker and
      immunotherapy target. The present study revealed that GAGE gene is unique to
      primate lineage. At least 15 duplicates with low divergence were found to be
      clustered in human X chromosome, while chimpanzee and macaque has 3 and 4 in a
      similar manner. The phylogenetic tree for the duplicates was constructed and the
      age of the duplication events was estimated, which was ranged from 4 million
      years ago to present. The Ka/Ks value of the duplicates was significantly greater
      than 1, indicating that GAGE family is under positive selection. Based on this
      study, GAGE may contribute to the characteristics of primate species, and the
      role of GAGE gene in evolution and in the genesis of gametid and tumor deserves
      further investigation.

PMID- 17548325
TI  - [Molecular genetic characteristic of bovine HTR1B gene].
AB  - The aim of the present study was to identify and characterize polymorphisms
      within the coding region and the 3' flanking region of the bovine serotonin
      receptor 1B gene among different cattle breeds. Four DNA fragments were amplified
      by polymerase chain reaction and then used for polymorphism identification by
      SSCP. The fragments showing different SSCP patterns were sequenced. And a total
      of six SNPs (G205T, C507T, C546G, C744T, G816A and G942A) were detected. The SNPs
      were at Hardy-Weinberg equilibrium except C507T and C546G in all genetic
      population. The frequencies of allele 205T of Holstein were much higher than that
      of the other six beef cattle populations. Almost the PIC of all SNPs were not
      more than 0.10 except that of G205T in Holstein cows, which indicated the bovine
      HTR1B gene was conserved.

PMID- 17548326
TI  - [Knock out of bovine beta casein gene by homologous recombination].
AB  - It has been reported that homologous recombination with Red system has been
      successfully used for knock-out. We try to work on the construction of the
      expression vector of Mammary Gland with Red system. This study takes CSN2 as a
      vector for gene target, which contains the complete bovine beta casein gene.
      Different homologous arms were designed and the CDS region of the beta casein
      gene was successfully knocked out. The efficiency was also explored for knocking
      out different DNA fragment. Based on the study, it is very convenient for making
      a deep research of the foreign gene expression under the regulation of CSN2
      flanking region.

PMID- 17548327
TI  - [Expression of CYP3A29 mRNA in Chinese experimental miniature pig's livers
      quantitated with real-time reverse transcription polymerase chain reaction].
AB  - CYP3A29 is the most important key enzyme for drug metabolism in pig's liver.
      Research of the characters of CYP3A29 mRNA expression in Chinese experimental
      miniature pig's livers is significant for evaluating it whether suitable for
      experimental model for drug metabolism mediated by human CYP3A4 enzyme. In this
      study, the levels of CYP3A29 mRNA expression in livers of Bama miniature pigs,
      Guizhou miniature pigs and Rongchang pigs were studied by TaqMan-mediated
      quantitative RT-PCR. Results indicated that the CYP3A29 mRNA expression levels in
      livers of these species were close to literatures of human. Levels of CYP3A29
      mRNA expression were similar among livers of Bama miniature pigs, Guizhou
      miniature pigs and Rongchang pigs, but interindividual variations were quite
      large. It was suggested that Bama miniature pigs and Guizhou miniature pigs were
      both feasible for experimental animal model for evaluating drug metabolism in
      some degree.

PMID- 17548328
TI  - [The mutation site analysis on CAPN1 gene of Wild boar, Min pig and Yorkshire].
AB  - In order to further evaluate the relationship between the variations of CAPN1
      gene and meat tenderness, the CAPN1 genomic sequences were cloned and sequenced,
      its CDS was analyzed with PCR-SSCP, and the genotype analyses covered 109
      individuals from Wild boar, Min pig and Yorkshire. Fifteen of total 21 introns
      were cloned. Five pairs polymorphic primers for PCR-SSCP analysis were designed
      based on the CDS of CAPN1 from GenBank and the cloned introns. Eight SNPs,
      resulting from single point mutation G to C, C to T, T to C, G to A, G to A, G to
      A, C to T and C to T at the base position 161 in exon2, 60 in exon5, 96 in exon5,
      119 in exon5, 270 in intron8, 83 in exon10, 126 in exon13 and 138 in exon13
      respectively, were identified, and 3 of which are missense mutations resulting to
      amino acid substitutions of S/T, G/E, V/I at the amino acid position of 54, 192
      and 363 respectively. chi2 analysis showed that the distribution of genotypes
      among Yorkshire, Min pig and Wild boar are extremely significant difference,
      while there are no significant difference be-tween Min pig and Wild boar except
      in the S1 primer. The polymorphic sites may be used as molecular markers for meat
      tenderness and pork quality.

PMID- 17548329
TI  - [Genetic diversity of red jungle fowl in China (Gallus gallus spadiceus) and red
      jungle fowl (Gallus gallus gallus) in Thailand].
AB  - Genetic diversity of red jungle fowl in China (Gallus gallus spadiceus) and red
      jungle fowl in Thailand (Gallus gallus gallus) was evaluated with 29
      microstaellite loci, the genetic variability within subspecies and genetic
      differentiation between subspecies were estimated. The results showed that the
      168 alleles were amplified with the number of alleles per locus from 2 to 13. The
      average expected heterozygosity and polymorphism information content (PIC) of all
      loci were 0.5780 and 0.53, respectively. The mean numbers of effective alleles of
      red jungle fowl in China and red jungle fowl in Thailand were 5.55 and 6.38. The
      heterozygosity and the genetic diversity of the two subspecies were high. Genetic
      differentiation index (FST) of these populations was 0.194 (P<0.01). Reynolds'
      genetic distance and gene flow between the two populations were 0.157 and 1.040,
      respectively. Based on these results, genetic structure and significant genetic
      differentiation of red jungle fowl in China were different from red jungle fowl
      in Thailand. The results of this study did not support to identify these red
      jungle fowl subspecies as the same subspecies, but supported the theory that
      Chinese domestic fowls have independent origin.

PMID- 17548330
TI  - [SNPs of myostatin gene and its genetic effects on carcass traits in chicken].
AB  - Two polymorphic sites in the first exon 1 of MSTN gene in 180 Wenling grass
      chicken including 3 lines were studied by PCR-RFLP method,and its genetic effects
      on carcass traits were researched. The results showed that 2 genotypes (MN and
      NN) in G(2100)A locus were identified by Bsh1236 I and 3 genotypes (AA, AB and
      BB) in G(2109)A locus were identified by Msp I, and 5 genotypes were emerged
      while com-analyzing 2 loci. The chi2 test indicated genotype frequencies had no
      significant deviation (P > 0.05) among lines. The analysis of variance showed
      that the different genotypes had significant deviation (P <0.01 or P < 0.05) in
      carcass percent. The multiple comparisons were made. The abdominal fat weight and
      carcass percent of heterozygosis MN were significantly higher (P<0.05) than that
      of mutant NN,and the breast muscle weight and breast muscle percent of
      heterozygosis AB were significantly higher (P < 0.01 or P<0.05) than that of AA
      individuals. In addition,the abdominal fat weight and abdominal fat percent of AA
      individuals were significantly higher (P<0.01) than that of mutant BB
      individuals,but BB individuals were significantly lower (P<0.05) than AA and AB
      individuals in leg muscle weight trait. The abdominal fat weight,abdominal fat
      percent and breast muscle percent of genotype NA/MA individuals were
      significantly higher or lower (P<0.01) than those in other genotype individuals
      while com-analyzing 2 loci.

PMID- 17548331
TI  - [SGP polymorphism in cultivated naked barley from Qinghai-Tibet plateau in China
      and the relationship between SGPs and starch content].
AB  - Starch granule proteins (SGPs) are minor components bound with starch granule,
      which mutation may be related to starch properties. This study investigated the
      variation of SGPs in cultivated naked barley from Qinghai-Tibet Plateau in China
      for the first time, and the relationship between SGPs and starch content was
      preliminarily done. Ten major SGPs and 16 types of patterns were present in 66
      cultivated naked varieties, indicating SGPs in cultivated naked barley from
      Qinghai-Tibet Plateau in China are polymorphic. SGPs in Tibet and Sichuan naked
      barley were greatly different and SGPs were specific to origin of site.
      Significance test analysis demonstrates SGPs described in this study except for
      SGP1 may be related with the variation of starch content in different naked
      barley.

PMID- 17548332
TI  - [Cloning and characterization of RZF71 encoding a C2H2-type zinc finger protein
      from rice].
AB  - A rice zinc-finger protein gene, RZF71, encoding the C2H2-type zinc-finger
      transcription factor was isolated from rice (Oryza sativa L. subs. Japonica) by
      RT-PCR approach. Gene RZF71 encodes a 25 kDa protein with 250 amino acids, which
      contains two typical C2H2 zinc finger domains. The expression profiling showed
      that RZF71 was constitutively expressed in roots, culms, leaves, and flowering
      spikes. The semi-quantitative RT-PCR assay showed RZF71 was strongly induced by
      high-salinity and 20% PEG6000 treatments, but not regulated by low temperature
      and ABA (abscisic acid) treatments. Tran-sient expression of the RZF71-GFP
      protein in onion epidermal cell showed that RZF71 was localized in cell nuclei.
      These results indicated that the RZF71 may play an important role in rice
      responses to salt and osmotic stresses as a transcription factor.

PMID- 17548333
TI  - [Comparative analysis of rDNA distribution in metaphase chromosomes of
      Cucurbitaceae species].
AB  - Fluorescence in situ hybridization (FISH) and double FISH experiments were
      carried out to ascertain the chromosomal distribution patterns of the 45S and 5S
      ribosomal DNAs in the three species of Cucurbitaceae. Five pairs of 45S rDNA loci
      and two pairs of 5S rDNA signals were detected on chromosomes of Cucurbita
      moschata Duch. Luffa cylindrical Roem. contained five pairs of 45S rDNA loci and
      one pair of 5S rDNA loci. In Benincasa hispida Cogn., two pairs of 45S rDNA sites
      and one pair of 5S rDNA site were detected. In this species, 5S rDNA and one pair
      of the 45S loci were collocated closely in chromosome 7S. 45S rDNA chromosomal
      distribution patterns were highly conserved among the three species, althoufh
      their number varied markedly. The 5S rDNA sites on chromosomes among the three
      species were highly polymorphic. We further discussed differentially evolutionary
      processes of 45S and 5S rDNA in plant genomes.

PMID- 17548334
TI  - [Molecular cloning and characterization of BcMYBogu, a novel member of the MYB
      family involved in OguCMS in Brassica campestris ssp. chinensis].
AB  - In the attempt to elucidate the molecular mechanism of CMS. Ogura cytoplasmic
      male sterile (OguCMS) lines were obtained in Chinese cabbage after interspecific
      hybridization between Brassica. napus L. OguCMS and B. campestris ssp. chinensis
      followed by recurrent backcross with B. campestris ssp. chinensis as the pollen
      donor. The CMS lines were significantly characterized by the whitish anther and
      indehiscence of anther. The tapetal hypertrophy with excess vacuola-tion was the
      first observed defective soon after the tetrad stage, subsequently the
      microspores defected in pollen wall forma-tion, and later the cytoplasm detached
      from the exine wall and underwent degeneration. With aid of cDNA-AFLP and RACE
      approaches, we cloned the BcMYBogu(GenBank accession No: EF127861) in Chinese
      cabbage, which is premature expressed in early and middle stage floral buds of
      OguCMS lines, and predicted to encode a novel protein with a DNA binding domain:
      SH[AL]QKY[RF] motif at the N-terminus. Phylogenetic comparison revealed that the
      BcMYBogu was clustered with AtMYB32, AtMYB26 and AtMYB4, which were indicated to
      be involved in male sterility in Arabidopsis thaliana. The BcMYBogu transcript
      was detected in rosette leaves, floral buds and stems by RT-PCR analysis.
      Compared with the maintainer, the expression level of BcMYBogu was increased in
      these organs, especially in floral buds of OguCMS lines. Our investigation
      suggests that BcMYBogu is a new member of the MYB family involved in male
      sterility in Chinese cabbage.

PMID- 17548335
TI  - [Study of hrpN(CSDS001) and the gene expression profile of Arabidopsis thaliana
      induced by Harpin(CSDS001)].
AB  - Erwinia carotovora subsp. carotovora CSDS001 elicits hypersensitive reaction (HR)
      in tobacco. From the genomic libraries of Erwinia carotovora subsp. carotovora
      CSDS001, the hrpNCSDS001 gene (GenBank number AY939927), was isolated. The
      hrpNCSDS001 fusion protein was produced in Escherichia coli, and was used to
      induce HR by injecting into tobacco. We further examined the global regulation of
      Arabidopsis thaliana genes in response to HarpinCSDS001 at a concentration of 30
      miccrog/mL. We indicated that 912, 1787, 2393, 1833 and 1,755 genes that were
      regulated significantly (log ratio <or=-1 or >or=1) at 3 h, 12 h, 24 h, 36 h and
      48 h respectively after the treatment. Analysis of some transcription factors
      (TF) showed that 13 TF families responded to HarpinCSDS001 including ZIM, BES1,
      TCP, C2C2, AP2/EREBP, WRKY, bHLH, bZIP, GARP, MYB, NAC, HB, C2H2. These families
      mainly function in biological processes of plant defense, pho
      tosynthesisdevelopment and flowering.

PMID- 17548336
TI  - [Characterization of antigenic epitopes of ORF2 encoded proteins of hepatitis E
      virus genotype 4 identified in China].
AB  - To characterize antigenic epitopes of hepatitis E virus (HEV) genotype 4 that was
      first identified in China a few years ago, a recombinant protein, p166Chn,
      encoded by HEV genotype 4 ORF2 was used to prepare anti-p166Chn McAbs.
      Simultaneously, twenty N- or C-terminal truncated p166Chn proteins were
      generated. Immunoreactivity between the McAbs and the truncated proteins as well
      as seven p166 recombinant proteins derived from different HEV genotypes and
      subgenotypes was detected by indirect ELISA, Western blot and competition
      inhibition ELISA. Two reactive profiles were observed with different McAbs and
      different truncated proteins. The McAbs, represented by 1G10, reacted with those
      N-terminal truncated proteins beginning at upstream of aa477 and those C-terminal
      truncated proteins ending at down-stream of aa613, suggesting that the epitope
      recognized by 1G10 relied on the region of aa477aa613 and was conformation
      dependent. While McAb 2F11 was reactive to those truncated p166Chn proteins
      beginning at upstream of aa474 or ending at downstream of aa617, indicating that
      the epitope recognized by 2F11 was also conformation-dependent and relied on a
      longer peptide of aa474aa617. However, the two groups of McAbs didn't inhibit
      each other when tested by a competition inhibition ELISA, which confirmed the
      different spatial positions of the two epitopes. Furthermore, when p166 proteins
      derived from different HEV genotypes and subtypes were applied, all of the McAbs
      prepared against pChn166 of genotype 4 identified in China could react with the
      proteins of genotype 1, 2 and 3 distributed worldwide. The data suggested that
      the two identified epitopes were HEV genotype-common and played significant
      effects on cross immunoreactivity between different HEV genotypes.

PMID- 17548337
TI  - [Genetic co-adaptability among structural genes under the condition of genetic
      disequilibrium].
AB  - Genetic co-adaptability of colony gene bank is formed in the process of system
      evolvement, and it is a part of the attribute of gene bank, just as the gene
      frequency of every locus. With the genetic co-adaptability of loci combination
      under the condition of genetic disequilibrium, the genesis evolution and the
      system status of colony could be analyzed; through the study of genetic co
      adaptability, the veracity of the economy character mark could be improved. We
      summarized about the concept, the basic and the actuality of genetic co
      adaptability.

PMID- 17548338
TI  - An unusual cause of left atrial mass.

PMID- 17548339
TI  - Biventricular rupture with extracardiac left-to-right shunt in the setting of an
      acute myocardial infarction.

PMID- 17548340
TI  - A prominent coronary Thebesian system.

PMID- 17548341
TI  - Setting a standard of affordability for health insurance coverage.
AB  - Recently, Massachusetts passed landmark legislation designed to expand health
      insurance coverage. This legislation includes a requirement that all adults
      enroll in a health insurance plan. This mandate takes effect only if an
      "affordable" plan is available. The definition of affordability for individuals
      and families of different incomes or circumstances is a critical decision in
      implementation and is relevant to any state or federal reform requiring
      individual premium or cost-sharing contributions, or both. This analysis was done
      to assist the policy design process in Massachusetts and delineates an
      empirically based approach to setting affordability standards.

PMID- 17548342
TI  - CD27-CD70 interactions sensitise naive CD4+ T cells for IL-12-induced Th1 cell
      development.
AB  - Stimulation of CD27, a member of the tumour necrosis factor receptor family, by
      its ligand CD70 induces expansion of IFNgamma secreting CD4+ and CD8+ T cells in
      vivo. We here analysed the mechanisms through which CD27 mediates this effect.
      CD27 co-stimulation induced cell division but did not directly instruct naive
      CD4+ T cells to differentiate into IFNgamma-producing Th1 cells. Rather, in
      concert with signals delivered through the TCR-CD3 complex, CD27 co-stimulation
      enhanced the Th1-specific transcription factor T-bet and caused up-regulation of
      the IL-12Rbeta2 chain. Consequently, CD27-costimulated T cells yielded vast
      numbers of IFNgamma-secreting cells in response to IL-12. Additionally, CD27
      ligation induced a strong up-regulation of Bcl-xL, but not of related anti
      apoptotic molecules. Thus, CD27-CD70 interactions may promote Th1 formation by
      permitting naive T cells to respond to differentiation signals and by promoting
      survival of activated effector T cells.

PMID- 17548343
TI  - Purification and characterization of cellular proteins associated with histone H4
      tails.
AB  - The histone H4 N-terminal tail has long been regarded as a major regulator in
      chromatin structure and function. Although the underlying mechanism has not been
      unraveled, an emerging body of evidence supports that H4 tail and its post
      translational modification function as a recruitment motif for key factors
      required for proper regulation of chromatin transcription. To investigate these
      aspects, we have generated HeLa cell lines that constitutively express ectopic H4
      tail domain for biochemical purification of proteins associated with H4 tail. We
      found that expressed H4 tails stably associate with sets of transcription
      regulatory factors and histone methyltransferases distinct from those that
      associate with histone H3 tails. Importantly, point mutations of four major
      lysine substrates to block cellular acetylation of ectopic H4 tail significantly
      inhibited the association of histone methyltransferases and sets of transcription
      activating factors, supporting a major role of acetylation on recruitmentbased
      action of H4 tail during transcription. Further, our transcription analysis
      revealed that the proteins associated with wild-type/acetylated H4 tail, but not
      with mutant/unacetylated H4 tail, can enhance p300-dependent chromatin
      transcription. Taken together, these findings demonstrate novel roles for H4 tail
      and its acetylation in mediating recruitment of multiple regulatory factors that
      can change chromatin states for transcription regulation.

PMID- 17548345
TI  - Mechanism of reversal of phospholamban inhibition of the cardiac Ca2+-ATPase by
      protein kinase A and by anti-phospholamban monoclonal antibody 2D12.
AB  - Our model of phospholamban (PLB) regulation of the cardiac Ca(2+)-ATPase in
      sarcoplasmic reticulum (SERCA2a) states that PLB binds to the Ca(2+)-free, E2
      conformation of SERCA2a and blocks it from transitioning from E2 to E1, the
      Ca(2+)-bound state. PLB and Ca(2+) binding to SERCA2a are mutually exclusive, and
      PLB inhibition of SERCA2a is manifested as a decreased apparent affinity of
      SERCA2a for Ca(2+). Here we extend this model to explain the reversal of SERCA2a
      inhibition that occurs after phosphorylation of PLB at Ser(16) by protein kinase
      A (PKA) and after binding of the anti-PLB monoclonal antibody 2D12, which
      recognizes residues 7-13 of PLB. Site-specific cysteine variants of PLB were co
      expressed with SERCA2a, and the effects of PKA phosphorylation and 2D12 on Ca(2+)
      ATPase activity and cross-linking to SERCA2a were monitored. In Ca(2+)-ATPase
      assays, PKA phosphorylation and 2D12 partially and completely reversed SERCA2a
      inhibition by decreasing K(Ca) values for enzyme activation, respectively. In
      cross-linking assays, cross-linking of PKA-phosphorylated PLB to SERCA2a was
      inhibited at only two of eight sites when conducted in the absence of Ca(2+)
      favoring E2. However, at a subsaturating Ca(2+) concentration supporting some E1,
      cross-linking of phosphorylated PLB to SERCA2a was attenuated at all eight sites.
      K(Ca) values for cross-linking inhibition were decreased nearly 2-fold at all
      sites by PLB phosphorylation, demonstrating that phosphorylated PLB binds more
      weakly to SERCA2a than dephosphorylated PLB. In parallel assays, 2D12 blocked PLB
      cross-linking to SERCA2a at all eight sites regardless of Ca(2+) concentration.
      Our results demonstrate that 2D12 restores maximal Ca(2+)-ATPase activity by
      physically disrupting the binding interaction between PLB and SERCA2a.
      Phosphorylation of PLB by PKA weakens the binding interaction between PLB and
      SERCA2a (yielding more PLB-free SERCA2a molecules at intermediate Ca(2+)
      concentrations), only partially restoring Ca(2+) affinity and Ca(2+)-ATPase
      activity.

PMID- 17548344
TI  - A kinase-anchoring protein 150 and calcineurin are involved in regulation of acid
      sensing ion channels ASIC1a and ASIC2a.
AB  - Acid-sensing ion channel (ASIC) 1a and ASIC2a are acid-sensing ion channels in
      central and peripheral neurons. ASIC1a has been implicated in long-term
      potentiation of synaptic transmission and ischemic brain injury, whereas ASIC2a
      is involved in mechanosensation. Although the biological role and distribution of
      ASIC1a and ASIC2a subunits in brain have been well characterized, little is known
      about the intracellular regulation of these ion channels that modulates their
      function. Using pulldown assays and mass spectrometry, we have identified A
      kinase-anchoring protein (AKAP)150 and the protein phosphatase calcineurin as
      binding proteins to ASIC2a. Extended pulldown and co-immunoprecipitation assays
      showed that these regulatory proteins also interact with ASIC1a. Transfection of
      rat cortical neurons with constructs encoding green fluorescent protein- or
      hemagglutinin-tagged channels showed expression of ASIC1a and ASIC2a in punctate
      and clustering patterns in dendrites that co-localized with AKAP150. Inhibition
      of protein kinase A binding to AKAPs by Ht-31 peptide reduces ASIC currents in
      cortical neurons and Chinese hamster ovary cells, suggesting a role of AKAP150 in
      association with protein kinase A in ASIC function. We also demonstrated a
      regulatory function of calcineurin in ASIC1a and ASIC2a activity. Cyclosporin A,
      an inhibitor of calcineurin, increased ASIC currents in Chinese hamster ovary
      cells and in cortical neurons, suggesting that activity of ASICs is inhibited by
      calcineurin-dependent dephosphorylation. These data imply that ASIC down
      regulation by calcineurin could play an important role under pathological
      conditions accompanying intracellular Ca(2+) overload and tissue acidosis to
      circumvent harmful activities mediated by these channels.

PMID- 17548346
TI  - Structure of the complex of the colicin E2 R-domain and its BtuB receptor. The
      outer membrane colicin translocon.
AB  - The crystal structure of the complex of the BtuB receptor and the 135-residue
      coiled-coil receptor-binding R-domain of colicin E3 (E3R135) suggested a novel
      mechanism for import of colicin proteins across the outer membrane. It was
      proposed that one function of the R-domain, which extends along the outer
      membrane surface, is to recruit an additional outer membrane protein(s) to form a
      translocon for passage colicin activity domain. A 3.5-A crystal structure of the
      complex of E2R135 and BtuB (E2R135-BtuB) was obtained, which revealed E2R135
      bound to BtuB in an oblique orientation identical to that previously found for
      E3R135. The only significant difference between the two structures was that the
      bound coiled-coil R-domain of colicin E2, compared with that of colicin E3, was
      extended by two and five residues at the N and C termini, respectively. There was
      no detectable displacement of the BtuB plug domain in either structure, implying
      that colicin is not imported through the outer membrane by BtuB alone. It was
      concluded that the oblique orientation of the R-domain of the nuclease E colicins
      has a function in the recruitment of another member(s) of an outer membrane
      translocon. Screening of porin knock-out mutants showed that either OmpF or OmpC
      can function in such a translocon. Arg(452) at the R/C-domain interface in
      colicin E2 was found have an essential role at a putative site of protease
      cleavage, which would liberate the C-terminal activity domain for passage through
      the outer membrane translocon.

PMID- 17548347
TI  - Neural precursor cells are protected from apoptosis induced by trophic factor
      withdrawal or genotoxic stress by inhibitors of glycogen synthase kinase 3.
AB  - Mechanisms controlling the survival of neural precursor cells (NPCs) are critical
      during brain development, in adults for neuron replenishment, and after
      transplantation for neuron replacement. This investigation found that glycogen
      synthase kinase 3 (GSK3) promotes apoptotic signaling in cultured NPCs derived
      from embryonic mouse brain subjected to two common apoptotic conditions, trophic
      factor withdrawal and genotoxic stress. Trophic factor withdrawal activated GSK3
      and the key apoptosis mediators Bax and caspase-3. Pharmacological inhibition of
      GSK3 activity produced dramatic reductions in the activation of Bax and caspase-3
      and NPC death after trophic factor withdrawal. Trophic factor withdrawal-induced
      apoptosis was delayed in Bax knock-out NPCs, but GSK3 inhibitors provided
      additional protection. Genotoxic stress induced by camptothecin treatment of NPCs
      stabilized p53, which formed a complex with GSK3beta and activated Bax and
      caspase-3. Camptothecin-induced activation of caspase-3 was reduced by GSK3
      inhibitors in both bax(+)(/)(+) and bax(-/-) NPCs. Thus, NPCs are sensitive to
      loss of trophic factors and genotoxic stress, and inhibitors of GSK3 are capable
      of enhancing NPC survival.

PMID- 17548348
TI  - Properties of RNA polymerase II elongation complexes before and after the P-TEFb
      mediated transition into productive elongation.
AB  - The positive transcription elongation factor, P-TEFb, controls the fraction of
      initiated RNA polymerase II molecules that enter into the productive mode of
      elongation necessary to generate mRNAs. To better understand the mechanism of
      this transition into productive elongation we optimized a defined in vitro
      transcription system and compared results obtained with it to those obtained with
      a crude system. We found that controlling the function of TFIIF is a key aspect
      of RNA polymerase II elongation control. Before P-TEFb function, early elongation
      complexes under the control of negative factors are completely unresponsive to
      the robust elongation stimulatory activity of TFIIF. P-TEFb-mediated
      phosphorylation events, targeting the elongation complex containing DSIF and
      NELF, reverse the negative effect of DSIF and NELF and simultaneously facilitate
      the action of TFIIF. We also found that productive elongation complexes are
      completely resistant to negative elongation factors. Our data suggest that an
      additional factor(s) is involved in establishing the unique resistance activities
      of the elongation complexes before and after P-TEFb function. Furthermore, we
      provide evidence for the existence of another positive activity required for
      efficient function of P-TEFb. A model of the mechanism of P-TEFb-mediated
      elongation control is proposed in which P-TEFb induces the transition into
      productive elongation by changing the accessibility of elongation factors to
      elongation complexes. Our results have uncovered important properties of
      elongation complexes that allow a more complete understanding of how P-TEFb
      controls the elongation phases of transcription by RNA polymerase II.

PMID- 17548350
TI  - Redox regulation of cAMP-dependent protein kinase signaling: kinase versus
      phosphatase inactivation.
AB  - Many components of cellular signaling pathways are sensitive to regulation by
      oxidation and reduction. Previously, we described the inactivation of cAMP
      dependent protein kinase (PKA) by direct oxidation of a reactive cysteine in the
      activation loop of the kinase. In the present study, we demonstrate that in HeLa
      cells PKA activity follows a biphasic response to thiol oxidation. Under mild
      oxidizing conditions, or short exposure to oxidants, forskolin-stimulated PKA
      activity is enhanced. This enhancement was blocked by sulfhydryl reducing agents,
      demonstrating a reversible mode of activation. In contrast, forskolin-stimulated
      PKA activity is inhibited by more severe oxidizing conditions. Mild oxidation
      enhanced PKA activity stimulated by forskolin, isoproterenol, or the cell
      permeable analog, 8-bromo-cAMP. When cells were lysed in the presence of
      serine/threonine phosphatase inhibitor, NaF, the PKA-enhancing effect of
      oxidation was blunted. These results suggest oxidation of a PKA-counteracting
      phosphatase may be inhibited, thus enhancing the apparent kinase activity. Using
      an in vivo PKA activity reporter, we demonstrated that mild oxidation does indeed
      prolong the PKA signal induced by isoproterenol by inhibiting counteracting
      phosphatase activity. The results of this study demonstrate in live cells a
      unique synergistic mechanism whereby the PKA signaling pathway is enhanced in an
      apparent biphasic manner.

PMID- 17548349
TI  - The transition to an elongation complex by T7 RNA polymerase is a multistep
      process.
AB  - During the transition from an initiation complex to an elongation complex (EC),
      T7 RNA polymerase undergoes major conformational changes that involve
      reorientation of a "core" subdomain as a rigid body and extensive refolding of
      other elements in the 266 residue N-terminal domain. The pathway and timing of
      these events is poorly understood. To examine this, we introduced proline
      residues into regions of the N-terminal domain that become alpha-helical during
      the reorganization and changed the charge of a key residue that interacts with
      the RNA:DNA hybrid 5 bp upstream of the active site in the EC but not in the
      initiation complex. These alterations resulted in a diminished ability to make
      products >5-7 nt and/or a slow transition through this point. The results
      indicate that the transition to an EC is a multistep process and that the
      movement of the core subdomain and reorganization of certain elements in the N
      terminal domain commence prior to promoter release (at 8-9 nt).

PMID- 17548351
TI  - G Protein betagamma subunits augment UVB-induced apoptosis by stimulating the
      release of soluble heparin-binding epidermal growth factor from human
      keratinocytes.
AB  - UV radiation induces various cellular responses by regulating the activity of
      many UV-responsive enzymes, including MAPKs. The betagamma subunit of the
      heterotrimeric GTP-binding protein (Gbetagamma) was found to mediate UV-induced
      p38 activation via epidermal growth factor receptor (EGFR). However, it is not
      known how Gbetagamma mediates the UVB-induced activation of EGFR, and thus we
      undertook this study to elucidate the mechanism. Treatment of HaCaT-immortalized
      human keratinocytes with conditioned medium obtained from UVB-irradiated cells
      induced the phosphorylations of EGFR, p38, and ERK but not that of JNK. Blockade
      of heparin-binding EGF-like growth factor (HB-EGF) by neutralizing antibody or
      CRM197 toxin inhibited the UVB-induced activations of EGFR, p38, and ERK in
      normal human epidermal keratinocytes and in HaCaT cells. Treatment with HB-EGF
      also activated EGFR, p38, and ERK. UVB radiation stimulated the processing of pro
      HB-EGF and increased the secretion of soluble HB-EGF in medium, which was
      quantified by immunoblotting and protein staining. In addition, treatment with
      CRM179 toxin blocked UV-induced apoptosis, but HB-EGF augmented this apoptosis.
      Moreover, UVB-induced apoptosis was reduced by inhibiting EGFR or p38. The
      overexpression of Gbeta(1)gamma(2) increased EGFR-activating activity and soluble
      HB-EGF content in conditioned medium, but the sequestration of Gbetagamma by the
      carboxyl terminus of G protein-coupled receptor kinase 2 (GRK2ct) produced the
      opposite effect. The activation of Src increased UVB-induced, Gbetagamma-mediated
      HB-EGF secretion, but the inhibition of Src blocked that. Overexpression of
      Gbetagamma increased UVB-induced apoptosis, and the overexpression of GRK2ct
      decreased this apoptosis. We conclude that Gbetagamma mediates UVB-induced human
      keratinocyte apoptosis by augmenting the ectodomain shedding of HB-EGF, which
      sequentially activates EGFR and p38.

PMID- 17548352
TI  - A transition state analogue of 5'-methylthioadenosine phosphorylase induces
      apoptosis in head and neck cancers.
AB  - Methylthio-DADMe-immucillin-A (MT-DADMe-ImmA) is an 86-pm inhibitor of human 5'
      methylthioadenosine phosphorylase (MTAP). The sole function of MTAP is to recycle
      5'-methylthioadenosine (MTA) to S-adenosylmethionine. Treatment of cultured cells
      with MT-DADMe-ImmA and MTA inhibited MTAP, increased cellular MTA concentrations,
      decreased polyamines, and induced apoptosis in FaDu and Cal27, two head and neck
      squamous cell carcinoma cell lines. The same treatment did not induce apoptosis
      in normal human fibroblast cell lines (CRL2522 and GM02037) or in MCF7, a breast
      cancer cell line with an MTAP gene deletion. MT-DADMe-ImmA alone did not induce
      apoptosis in any cell line, implicating MTA as the active agent. Treatment of
      sensitive cells caused loss of mitochondrial inner membrane potential, G(2)/M
      arrest, activation of mitochondria-dependent caspases, and apoptosis. Changes in
      cellular polyamines and MTA levels occurred in both responsive and nonresponsive
      cells, suggesting cell-specific epigenetic effects. A survey of aberrant DNA
      methylation in genomic DNA using a microarray of 12,288 CpG island clones
      revealed decreased CpG island methylation in treated FaDu cells compared with
      untreated cells. FaDu tumors in a mouse xenograft model were treated with MT
      DADMe-ImmA, resulting in tumor remission. The selective action of MT-DADMe-ImmA
      on head and neck squamous cell carcinoma cells suggests potential as an agent for
      treatment of cancers sensitive to reduced CpG island methylation.

PMID- 17548353
TI  - Doc2beta is a novel Munc18c-interacting partner and positive effector of syntaxin
      4-mediated exocytosis.
AB  - The widely expressed Sec/Munc18 (SM) protein Munc18c is required for SNARE
      mediated insulin granule exocytosis from islet beta cells and GLUT4 vesicle
      exocytosis in skeletal muscle and adipocytes. Although Munc18c function is known
      to involve binding to the t-SNARE Syntaxin 4, a paucity of Munc18c-binding
      proteins has restricted elucidation of the mechanism by which it facilitates
      these exocytosis events. Toward this end, we have identified the double C2 domain
      protein Doc2beta as a new binding partner for Munc18c. Unlike its granule/vesicle
      localization in neuronal cells, Doc2beta was found principally in the plasma
      membrane compartment in islet beta cells and adipocytes. Moreover, co
      immunoprecipitation and GST interaction assays showed Doc2beta-Munc18c binding to
      be direct and complexes to be devoid of Syntaxin 4. Supporting the notion of
      Munc18c binding with Syntaxin 4 and Doc2beta in mutually exclusive complexes, in
      vitro competition with Syntaxin 4 effectively displaced Munc18c from binding to
      Doc2beta. The second C2 domain (C2B) of Doc2beta and an N-terminal region of
      Munc18c were sufficient to confer complex formation. Disruption of endogenous
      Munc18c-Doc2beta complexes by addition of the Doc2beta binding domain of Munc18c
      (residues 173-255) was found to selectively inhibit glucose-stimulated insulin
      release. Moreover, increased expression of Doc2beta enhanced glucose-stimulated
      insulin secretion by approximately 40%, whereas siRNA-mediated depletion of
      Doc2beta attenuated insulin release. All changes in secretion correlated with
      parallel alterations in VAMP2 granule docking with Syntaxin 4. Taken together,
      these data support a model wherein Munc18c transiently switches from association
      with Syntaxin 4 to association with Doc2beta at the plasma membrane to facilitate
      exocytosis.

PMID- 17548354
TI  - Tripartite chimeras comprising functional domains derived from the cytosolic
      NADPH oxidase components p47phox, p67phox, and Rac1 elicit activator-independent
      superoxide production by phagocyte membranes: an essential role for anionic
      membrane phospholipids.
AB  - The superoxide-generating NADPH oxidase is converted to an active state by the
      assembly of a membrane-localized cytochrome b(559) with three cytosolic
      components: p47(phox), p67(phox), and GTPase Rac1 or Rac2. Assembly involves two
      sets of protein-protein interactions: among cytosolic components and among
      cytosolic components and cytochrome b(559) within its lipid habitat. We
      circumvented the need for interactions among cytosolic components by constructing
      a recombinant tripartite chimera (trimera) consisting of the Phox homology (PX)
      and Src homology 3 (SH3) domains of p47(phox), the tetratricopeptide repeat and
      activation domains of p67(phox), and full-length Rac1. Upon addition to phagocyte
      membrane, the trimera was capable of oxidase activation in vitro in the presence
      of an anionic amphiphile. The trimera had a higher affinity (lower EC(50)) for
      and formed a more stable complex (longer half-life) with cytochrome b(559)
      compared with the combined individual components, full-length or truncated.
      Supplementation of membrane with anionic but not neutral phospholipids made
      activation by the trimera amphiphile-independent. Mutagenesis, truncations, and
      domain replacements revealed that oxidase activation by the trimera was dependent
      on the following interactions: 1) interaction with anionic membrane phospholipids
      via the poly-basic stretch at the C terminus of the Rac1 segment; 2) interaction
      with p22(phox) via Trp(193) in the N-terminal SH3 domain of the p47(phox)
      segment, supplementing the electrostatic attraction; and 3) an intrachimeric bond
      among the p67(phox) and Rac1 segments complementary to their physical fusion. The
      PX domain of the p47(phox) segment and the insert domain of the Rac1 segment made
      only minor contributions to oxidase assembly.

PMID- 17548355
TI  - Accelerating amyloid-beta fibrillization reduces oligomer levels and functional
      deficits in Alzheimer disease mouse models.
AB  - Many proteins suspected of causing neurodegenerative diseases exist in diverse
      assembly states. For most, it is unclear whether shifts from one state to another
      would be helpful or harmful. We used mutagenesis to change the assembly state of
      Alzheimer disease (AD)-associated amyloid-beta (Abeta) peptides. In vitro, the
      "Arctic" mutation (AbetaE22G) accelerated Abeta fibrillization but decreased the
      abundance of nonfibrillar Abeta assemblies, compared with wild-type Abeta. In
      human amyloid precursor protein (hAPP) transgenic mice carrying mutations
      adjacent to Abeta that increase Abeta production, addition of the Arctic mutation
      markedly enhanced the formation of neuritic amyloid plaques but reduced the
      relative abundance of a specific nonfibrillar Abeta assembly (Abeta*56). Mice
      overexpressing Arctic mutant or wild-type Abeta had similar behavioral and
      neuronal deficits when they were matched for Abeta*56 levels but had vastly
      different plaque loads. Thus, Abeta*56 is a likelier determinant of functional
      deficits in hAPP mice than fibrillar Abeta deposits. Therapeutic interventions
      that reduce Abeta fibrils at the cost of augmenting nonfibrillar Abeta assemblies
      could be harmful.

PMID- 17548356
TI  - Membrane glycoprotein M6a interacts with the micro-opioid receptor and
      facilitates receptor endocytosis and recycling.
AB  - Using a yeast two-hybrid screen, the neuronal membrane glycoprotein M6a, a member
      of the proteolipid protein family, was identified to be associated with the mu
      opioid receptor (MOPr). Bioluminescence resonance energy transfer and co
      immunoprecipitation experiments confirmed that M6a interacts agonist
      independently with MOPr in human embryonic kidney 293 cells co-expressing MOPr
      and M6a. Co-expression of MOPr with M6a, but not with M6b or DM20, exists in many
      brain regions, further supporting a specific interaction between MOPr and M6a.
      After opioid treatment M6a co-internalizes and then co-recycles with MOPr to cell
      surface in transfected human embryonic kidney 293 cells. Moreover, the
      interaction of M6a and MOPr augments constitutive and agonist-dependent
      internalization as well as the recycling rate of mu-opioid receptors. On the
      other hand, overexpression of a M6a-negative mutant prevents mu-opioid receptor
      endocytosis, demonstrating an essential role of M6a in receptor internalization.
      In addition, we demonstrated the interaction of M6a with a number of other G
      protein-coupled receptors (GPCRs) such as the delta-opioid receptor, cannabinoid
      receptor CB1, and somatostatin receptor sst2A, suggesting that M6a might play a
      general role in the regulation of certain GPCRs. Taken together, these data
      provide evidence that M6a may act as a scaffolding molecule in the regulation of
      GPCR endocytosis and intracellular trafficking.

PMID- 17548357
TI  - Blue light induces radical formation and autophosphorylation in the light
      sensitive domain of Chlamydomonas cryptochrome.
AB  - Cryptochromes are sensory blue light receptors mediating various responses in
      plants and animals. Studies on the mechanism of plant cryptochromes have been
      focused on the flowering plant Arabidopsis. In the genome of the unicellular
      green alga Chlamydomonas reinhardtii, a single plant cryptochrome, Chlamydomonas
      photolyase homologue 1 (CPH1), has been identified. The N-terminal 500 amino
      acids comprise the light-sensitive domain of CPH1 linked to a C-terminal
      extension of similar size. We have expressed the light-sensitive domain
      heterologously in Escherichia coli in high yield and purity. The 59-kDa protein
      bears exclusively flavin adenine dinucleotide in its oxidized state. Illumination
      with blue light induces formation of a neutral flavin radical with absorption
      maxima at 540 and 580 nm. The reaction proceeds aerobically even in the absence
      of an exogenous electron donor, which suggests that it reflects a physiological
      response. The process is completely reversible in the dark and exhibits a decay
      time constant of 200 s in the presence of oxygen. Binding of ATP strongly
      stabilizes the radical state after illumination and impedes the dark recovery.
      Thus, ATP binding has functional significance for plant cryptochromes and does
      not merely result from structural homology to DNA photolyase. The light-sensitive
      domain responds to illumination by an increase in phosphorylation. The
      autophosphorylation takes place although the protein is lacking its native C
      terminal extension. This finding indicates that the extension is dispensable for
      autophosphorylation, despite the role it has been assigned in mediating signal
      transduction in Arabidopsis.

PMID- 17548358
TI  - A functional role for p38 MAPK in modulating mitotic transit in the absence of
      stress.
AB  - Although p38 MAPK is known to be activated in response to various environmental
      stresses and to have inhibitory roles in cell proliferation and tumor
      progression, its role in cell cycle progression in the absence of stress is
      unknown in most cell types. In the case of G(2)/M cell cycle control, p38
      activation has been shown to trigger a rapid G(2)/M cell cycle checkpoint after
      DNA damage stress and a spindle checkpoint after microtubule disruption. In the
      course of our studies, we observed that p38 became actively phosphorylated, and
      its kinase activity increased transiently during G(2)/M cell cycle transition.
      Using an immunocytochemistry approach, the active form of p38 was found at the
      centrosome from late G(2) throughout mitosis, which suggests functional relevance
      for active p38 protein during mitotic entry. A closer examination reveals that
      p38 inhibition by pharmacologic inhibitors significantly accelerated the timing
      of mitotic entry. In addition, long term exposure of the inhibitor enhanced Cdc2
      activity. These results indicate that p38 activity during G(2)/M may be involved
      in a mechanism for fine tuning the initiation of mitosis and perhaps transit of
      mitosis. Consistent with our previous findings, Cdc25B was phosphorylated on
      serine 309 at the centrosome during G(2)/M when p38 was active at this site;
      Cdc25B phosphorylation inhibits Cdc25B activity, and this phosphorylation was
      found to be p38-dependent. Taken together, our findings suggest that p38
      regulates the timing of mitotic entry via modulation of Cdc25B activity under
      normal nonstress conditions.

PMID- 17548359
TI  - Mechanism of diacylglycerol-induced membrane targeting and activation of protein
      kinase Ctheta.
AB  - Protein kinase C (PKC) is a novel PKC that plays a key role in T lymphocyte
      activation. PKC has been shown to be specifically recruited to the immunological
      synapse in response to T cell receptor activation. To understand the basis of its
      unique subcellular localization properties, we investigated the mechanism of in
      vitro and cellular sn-1,2-diacylglycerol (DAG)-mediated membrane binding of PKC.
      PKC showed phosphatidylserine selectivity in membrane binding and kinase action,
      which contributes to its translocation to the phosphatidylserine-rich plasma
      membrane in HEK293 cells. Unlike any other PKCs characterized so far, the
      isolated C1B domain of PKC had much higher affinity for DAG-containing membranes
      than the C1A domain. Also, the mutational analysis indicates that the C1B domain
      plays a predominant role in the DAG-induced membrane binding and activation of
      PKC. Furthermore, the Ca(2+)-independent C2 domain of PKC has significant
      affinity for anionic membranes, and the truncation of the C2 domain greatly
      enhanced the membrane affinity and enzyme activity of PKC. In addition, membrane
      binding properties of Y90E and Y90F mutants indicate that phosphorylation of
      Tyr(90) of the C2 domain enhances the affinity of PKC for model and cell
      membranes. Collectively, these results show that PKC has a unique membrane
      binding and activation mechanism that may account for its subcellular targeting
      properties.

PMID- 17548360
TI  - Determinants of the anesthetic sensitivity of two-pore domain acid-sensitive
      potassium channels: molecular cloning of an anesthetic-activated potassium
      channel from Lymnaea stagnalis.
AB  - Certain two-pore domain K(+) channels are plausible targets for volatile general
      anesthetics, yet little is known at the molecular level about how these simple
      agents cause channel activation. The first anesthetic-activated K(+) current
      I(K(An)) that was characterized was discovered in the mollusk Lymnaea stagnalis
      and is remarkable for both its sensitivity to general anesthetics and its
      stereoselective responses to anesthetic enantiomers (Franks, N. P., and Lieb, W.
      R. (1988) Nature 333, 662-664 and Franks, N. P., and Lieb, W. R. (1991) Science
      254, 427-430). Here we report the molecular cloning of a two-pore domain K(+)
      channel LyTASK from L. stagnalis and show that, when expressed in HEK-293 cells,
      it displays the same biophysical characteristics as the anesthetic-activated K(+)
      current I(K(An)). Sequence analysis and functional properties show it to be a
      member of the TASK family of channels with approximately 47% identity at the
      amino acid level when compared with human TASK-1 and TASK-3. By using chimeric
      channel constructs and site-directed mutagenesis we have identified the specific
      amino acid 159 to be a critical determinant of anesthetic sensitivity, which,
      when mutated to alanine, essentially eliminates anesthetic activation in the
      human channels and greatly reduces activation in LyTASK. The L159A mutation in
      LyTASK disrupts the stereoselective response to isoflurane while having no effect
      on the pH sensitivity of the channel, suggesting this critical amino acid may
      form part of an anesthetic binding site.

PMID- 17548361
TI  - Kinetic characterization of tail swing steps in the ATPase cycle of Dictyostelium
      cytoplasmic dynein.
AB  - According to the power stroke model of dynein deduced from electron microscopic
      and fluorescence resonance energy transfer studies, the power stroke and the
      recovery stroke are expected to take place at the two isomerization steps of the
      ATPase cycle at the primary ATPase site. Here, we have conducted presteady-state
      kinetic analyses of these two isomerization steps with the single-headed motor
      domain of Dictyostelium cytoplasmic dynein by employing fluorescence resonance
      energy transfer to probe ATPase steps at the primary site and tail positions. Our
      results show that the recovery stroke at the first isomerization step proceeds
      quickly ( approximately 180 s(-1)), whereas the power stroke at the second
      isomerization step is very slow ( approximately 0.2 s(-1)) in the absence of
      microtubules, and that the presence of microtubules accelerates the second but
      not the first step. Moreover, a comparison of the microtubule-induced
      acceleration of the power stroke step and that of steady-state ATP hydrolysis
      implies the intriguing possibility that microtubules simultaneously accelerate
      the ATPase activity not only at the primary site but also at other site(s) in the
      motor domain.

PMID- 17548362
TI  - Analysis of the signals and mechanisms mediating nuclear trafficking of GATA-4.
      Loss of DNA binding is associated with localization in intranuclear speckles.
AB  - Nucleocytoplasmic transport of GATA-4 is important in maintaining and regulating
      normal cardiogenesis and heart function. This report investigates the detailed
      mechanisms of GATA-4 nuclear transport. We characterized a nonclassical nuclear
      localization signal between amino acids 270 and 324 that actively transports GATA
      4 into the nucleus of both HeLa cells and cardiac myocytes. Fine mapping studies
      revealed four crucial arginine residues within this region that mediate active
      transport predominantly through the nonclassical pathway via interaction with
      importin beta. These four residues were also essential for the DNA binding
      activity of GATA-4 and transcriptional activation of cardiac-specific genes.
      Interestingly, mutation of these residues not only inhibited DNA binding and gene
      transcription but also resulted in a preferential accumulation of the GATA-4
      protein in distinct subnuclear speckles. A cardiac myocyte-specific, chromosome
      maintenance region 1-dependent nuclear export signal consisting of three
      essential leucine residues was also identified. The current study provides
      detailed information on the nuclear shuttling pathways of GATA-4 that represents
      an additional mechanism of gene regulation.

PMID- 17548363
TI  - Clinical trial registration.

PMID- 17548364
TI  - Duplex ultrasonography, magnetic resonance angiography, and computed tomography
      angiography for diagnosis and assessment of symptomatic, lower limb peripheral
      arterial disease: systematic review.
AB  - OBJECTIVES: To determine the diagnostic accuracy of duplex ultrasonography,
      magnetic resonance angiography, and computed tomography angiography, alone or in
      combination, for the assessment of lower limb peripheral arterial disease; to
      evaluate the impact of these assessment methods on management of patients and
      outcomes; and to evaluate the evidence regarding attitudes of patients to these
      technologies and summarise available data on adverse events. DESIGN: Systematic
      review. METHODS: Searches of 11 electronic databases (to April 2005), six
      journals, and reference lists of included papers for relevant studies. Two
      reviewers independently selected studies, extracted data, and assessed quality.
      Diagnostic accuracy studies were assessed for quality with the QUADAS checklist.
      RESULTS: 107 studies met the inclusion criteria; 58 studies provided data on
      diagnostic accuracy, one on outcomes in patients, four on attitudes of patients,
      and 44 on adverse events. Quality assessment highlighted limitations in the
      methods and quality of reporting. Most of the included studies reported results
      by arterial segment, rather than by limb or by patient, which does not account
      for the clustering of segments within patients, so specificities may be
      overstated. For the detection of stenosis of 50% or more in a lower limb vessel,
      contrast enhanced magnetic resonance angiography had the highest diagnostic
      accuracy with a median sensitivity of 95% (range 92-99.5%) and median specificity
      of 97% (64-99%). The results were 91% (89-99%) and 91% (83-97%) for computed
      tomography angiography and 88% (80-98%) and 96% (89-99%) for duplex
      ultrasonography. A controlled trial reported no significant differences in
      outcomes in patients after treatment plans based on duplex ultrasonography alone
      or conventional contrast angiography alone, though in 22% of patients
      supplementary contrast angiography was needed to form a treatment plan. The
      limited evidence available suggested that patients preferred magnetic resonance
      angiography (with or without contrast) to contrast angiography, with half
      expressing no preference between magnetic resonance angiography or duplex
      ultrasonography (among patients with no contraindications for magnetic resonance
      angiography, such as claustrophobia). Where data on adverse events were
      available, magnetic resonance angiography was associated with the highest
      proportion of adverse events, but these were mild. The most severe adverse
      events, although rare, were mainly associated with contrast angiography.
      CONCLUSIONS: Contrast enhanced magnetic resonance angiography seems to be more
      specific than computed tomography angiography (that is, better at ruling out
      stenosis over 50%) and more sensitive than duplex ultrasonography (that is,
      better at ruling in stenosis over 50%) and was generally preferred by patients
      over contrast angiography. Computed tomography angiography was also preferred by
      patients over contrast angiography; no data on patients' preference between
      duplex ultrasonography and contrast angiography were available. Where available,
      contrast enhanced magnetic resonance angiography might be a viable alternative to
      contrast angiography.

PMID- 17548365
TI  - Vitamin D reserve is higher in women with endometriosis.
AB  - BACKGROUND: An immune-mediated defect in recognition and elimination of
      endometrial fragments refluxed in the peritoneal cavity has been hypothesized to
      play a crucial role in endometriosis development. Since vitamin D is an effective
      modulator of the immune system, we have hypothesized that the vitamin D status
      may have a role in the pathogenesis of endometriosis. METHODS: Women of
      reproductive age selected for surgery for gynecological indications were enrolled
      in this prospective cohort study. Serum levels of 25-hydroxyvitamin-D(3), 1,25
      dihydroxyvitamin-D(3) and Ca(2+) were assessed. RESULTS: Eighty-seven women with
      endometriosis and 53 controls were recruited. Mean (+/- SD) levels of 25
      hydroxyvitamin-D(3) in women with and without endometriosis were 24.9 +/- 14.8
      ng/ml and 20.4 +/- 11.8, respectively (P = 0.05). The Odds Ratio (95% Confidence
      Interval) for endometriosis in patients with levels exceeding the 75th percentile
      of the serum distribution of the molecule (28.2 ng/ml) was 4.8 (1.7-13.5). A
      positive gradient according to the severity of the disease was also documented. A
      trend towards higher levels of 1,25-dihydroxyvitamin-D(3) and Ca(2+) was observed
      in women with endometriosis, but differences did not reach statistical
      significance. As expected, serum concentrations of 25-hydroxyvitamin-D(3) and
      1,25-dihydroxyvitamin-D(3,) but not Ca(2+), are influenced by the season (P <
      0.001, P = 0.004, P = 0.57, respectively), while levels of the three molecules
      did not vary according to the phase of the menstrual cycle. CONCLUSIONS:
      Endometriosis is associated with higher serum levels of vitamin D.

PMID- 17548366
TI  - Families working it out: adolescents' views on communicating about donor-assisted
      conception.
AB  - BACKGROUND: Prompted by legislation in Victoria, Australia, permitting gamete
      donors to seek identifying details of people conceived from their gametes, this
      research investigated the views of adolescents from the general population on how
      parents can best talk to their donor-conceived adolescent children about their
      conception. METHODS: Qualitative interviews (six group discussions, n = two to
      six per group, and one individual interview) lasting c. 50 min with 25 secondary
      school students. RESULTS: Naive adolescents had views largely consistent with
      those of donor-conceived adults, for example, urging parental honesty, adaptation
      to individual children, and family cohesion. They identified the social father as
      the parent while acknowledging the significance of genetic connection to the
      donor. A minority asserted a preference for non-disclosure; all said that, if
      disclosed, it should be by parents. CONCLUSIONS: This small study contributes to
      increasing understanding of communication within families about donor-assisted
      conception.

PMID- 17548367
TI  - Estimating human ovarian non-growing follicle number: the application of modern
      stereology techniques to an old problem.
AB  - BACKGROUND Previous published reports on the number of non-growing follicles
      (NGFs) in the human ovary have employed model-based methods for number estimates.
      These methods are time-intensive, and require correction factors and assumptions
      that ultimately limit their accuracy. Here, we describe the modification,
      application and validation of a modern fractionator/optical disector technique
      for the estimation of human ovarian NGF number. METHODS Forty-eight pairs of
      normal human ovaries were collected from women (age 8-51 years) undergoing
      elective bilateral oophorectomy, organ donation, or from autopsy. After gross
      pathologic examination, systematic random sampling was utilized to obtain tissue
      for analysis by the fractionator/optical disector method. The precision of
      individual NGF counts was determined by calculating the observed coefficient of
      error (OCE). Intra-observer variability and variation in NGF number between
      ovaries within a pair were also determined. RESULTS The mean OCE was 16.6% with
      larger variations observed at lower follicle counts. In recount experiments of
      the same ovary, NGF number estimates varied by 15-29%, except at very low
      follicle counts where variation was greater, but absolute differences were small.
      There was no significant difference in NGF number between ovaries within a pair
      (Wilcoxon signed rank test, P = 0.81). CONCLUSIONS Modern stereology methods
      provide an unbiased, efficient method for estimating NGF number in the human
      ovary. Both ovaries within a pair contain similar numbers of NGFs.

PMID- 17548368
TI  - The role of the endometrium and embryo in human implantation.
AB  - Despite many advances in assisted reproductive technologies (ART), implantation
      rates are still low. The process of implantation requires a reciprocal
      interaction between blastocyst and endometrium, culminating in a small window of
      opportunity during which implantation can occur. This interaction involves the
      embryo, with its inherent molecular programme of cell growth and differentiation,
      and the temporal differentiation of endometrial cells to attain uterine
      receptivity. Implantation itself is governed by an array of endocrine, paracrine
      and autocrine modulators, of embryonic and maternal origin. Implantation failure
      is thought to occur as a consequence of impairment of embryo developmental
      potential and/or impairment of uterine receptivity and the embryo-uterine
      dialogue. Therefore a better comprehension of implantation, and the relative
      importance of the factors involved, is warranted. New techniques for monitoring
      changes in the endometrium and/or the embryo at the level of gene regulation and
      protein expression may lead to the identification of better markers for
      implantation. Moreover, the use of predictive sets of markers may prove to be
      more reliable than a single marker. Continuing refinements to ART protocols, such
      as optimizing ovarian stimulation regimens, the timing of human chorionic
      gonadotrophin injection, or the timing of embryo transfer, should help to
      increase implantation rates further.

PMID- 17548369
TI  - Topiramate (Topamax) reduces conditioned abstinence behaviours and handling
      induced convulsions (HIC) after chronic administration of alcohol in Swiss
      Webster mice.
AB  - Topiramate has emerged as one of the promising drugs for the treatment of
      alcoholism and alcohol addiction. Recent studies have shown that topiramate
      reduces harmful drinking and initiates abstinence in humans, but little is known
      as to why this drug is effective. AIMS: In the present study, we examined the
      effects of topiramate in reducing convulsions during alcohol withdrawal using a
      procedure called the handling-induced convulsion (HIC) test in male Swiss-Webster
      mice. In addition, we examined the ability of topiramate to reduce alcohol
      conditioned and anxiety related behaviours during conditioned abstinence using
      the elevated plus maze (EPM) test. METHODS: HICs were examined 10 h after the 3rd
      daily alcohol (2.5 g/kg; 20% w/v)+4 methylpyrazole (4MP) (9 mg/kg)
      intraperitoneal (i.p.) injection with topiramate (0, 10 or 20 mg/kg ip)
      administered 30 min before testing. In the EPM, alcohol (1.75 g/kg; 20%, i.p.) or
      saline was administered daily for 9 days and subjects were immediately placed on
      the maze. Anxiety related behaviours included the amount of time spent and number
      of entries in the open or closed arms and grooming bouts, and conditioned
      behaviours including the stretched-attend posture were examined 24 h after the
      last day of alcohol injection. RESULTS: Topiramate (10 and 20 mg/kg)
      significantly reduced HIC scores (P<0.05) compared to the alcohol/saline group.
      In the EPM, topiramate (20 mg/kg) reduced the stretched-attend postures (P<0.001)
      compared to the alcohol/saline group. CONCLUSION: These findings suggest that
      topiramate reduces HICs during alcohol withdrawal and alcohol-conditioned
      behaviours during conditioned abstinence in Swiss-Webster mice.

PMID- 17548370
TI  - Assessing basketball ability in players with mental retardation.
AB  - BACKGROUND: Although athletes with mental retardation (MR) have achieved an
      important role, literature concerning the evaluation tests in basketball is still
      poor. OBJECTIVE: To assess basketball ability before and after a 4-month training
      performed before championship for athletes with MR and to correlate ability
      variations with MR levels. METHODS: 15 trained basketball players with MR (11 men
      and 4 women; age range 21-43 years; MR: 3 mild, 8 moderate, 8 severe and 1
      profound). Athletes were tested before (pre) and after (post) 4 month training
      preceding the championship. The tests assessed 4 levels of ability, each one
      characterised by 4 fundamental areas of this game: ball handling, reception,
      passing and shooting. Each area was divided into 5 specific components. RESULTS:
      The team average score, based on the score of each athlete's 4 levels, improved
      by 6.6 points (41.6 (SD 11.9) vs 48.2 (14.7)). The comparison between pre and
      post scores in each level showed increases (p<0.01), especially in level II (14.4
      (3.5) vs 16.5 (3.3)) and in level III (7.1 (5.7) vs 9.2 (6.6)). Within level II,
      ball handling (3.67 (1.2) vs 4.37 (0.5); p<0.05) and passing (3.20 (1.2) vs 3.97
      (1.3); p<0.01) improved; in level III reception (3.21 (1.1) vs 3.73 (1.1); p =
      0.01) and shooting (1.82 (1.1) vs 2.45 (1.3); p<0.05) increased. CONCLUSIONS: A 4
      month training caused a general improvement, especially evident in levels II and
      III. Total score reached in level II was negatively correlated with MR level (r =
      -0.56; p<0.05), indicating that athletes with lower MR obtained higher scores.

PMID- 17548371
TI  - Bicuspid aortic valve in competitive athletes.
AB  - AIM: Bicuspid aortic valve (BAV) is a common congenital cardiac condition. The
      presence of BAV in non-elite athletes has been poorly investigated; it is usually
      asymptomatic until valvular stenosis, regurgitation or other vascular alterations
      are evident. DESIGN: Over a three-year period, 2273 competitive athletes were
      consecutively investigated with transthoracic echocardiography. The traditional
      parameters, the aortic root dimensions at four levels and the systolic and
      diastolic flow of aortic valve, were studied with continuous Doppler according to
      the echo guidelines. SETTING: The study protocol included all the non-elite
      athletes investigated for the first evaluation to obtain eligibility. PATIENTS:
      2273 competitive athletes aged 8-60 years from several sports and regularly
      trained were evaluated with anamnesis, clinical check-up and echocardiography in
      order to exclude subjects with systemic or congenital heart disease. RESULTS: BAV
      was diagnosed in 58 athletes (2.5%). Of these, nine had normal valvular function,
      47 had abnormal valvular function with mild-moderate aortic regurgitation, and
      two had moderate stenosis. Aortic root dimensions at all levels were
      significantly greater in athletes with BAV than in athletes with a normal
      tricuspid valve. No relation was found with age, body surface area, aortic
      regurgitation or years of training. CONCLUSIONS: BAV is a relatively common
      congenital cardiac disease in athletes and commonly asymptomatic for a long time.
      This study suggests the usefulness of evaluating young athletes using
      echocardiography at least once when they start their sporting activity.

PMID- 17548372
TI  - Consumption of anabolic steroids in sport, physical activity and as a drug of
      abuse: an analysis of the scientific literature and areas of research.
AB  - OBJECTIVE: The consumption of anabolic steroids (AS) has been growing
      continuously in recent years. It has gone beyond the sports world; AS are now
      widely used as drugs of abuse in connection with bodybuilding. This study sets
      out to assess the state of scientific research in the area. DESIGN: Bibliometrics
      were employed to evaluate the literature retrieved from the principal relevant
      bibliographic databases: MEDLINE, SportDiscus, the Science Citation Index
      Expanded and the Social Sciences Citation Index. The core journals were
      identified along with the leading authors and research groups and their
      institutional affiliations. Techniques based on social network analysis were
      applied in order to build up a concept map of research. RESULTS: 1325 documents
      were retrieved. They were produced by 3131 different researchers giving a
      Collaboration Index of 3.32. The institutions with the most productive authors
      were Ball State University (Muncie, IN, USA), the Ecole Nationale Veterinaire de
      Nantes (ENVN), the Institut Municipal dInvestigacio Medica (IMIM) (Barcelona,
      Spain), the Institute of Biochemistry of the German Sport University Cologne
      (DSHS), Iowa State University, Maastricht University and the University of Iowa.
      CONCLUSIONS: It was concluded that there has been an upward trend in the number
      of research projects. The sources used complemented one another, as 78.04% of the
      documents retrieved were unique to one source. The productivity ranking was
      headed by sports medicine journals, followed by journals of chemistry,
      physiology, endocrinology and substance abuse. Besides sporting activities, the
      most important research clusters were those connected with bodybuilding and with
      youth groups.

PMID- 17548373
TI  - Vicianin hydrolase is a novel cyanogenic beta-glycosidase specific to beta
      vicianoside (6-O-alpha-L-arabinopyranosyl-beta-D-glucopyranoside) in seeds of
      Vicia angustifolia.
AB  - The cyanogenic disaccharide glycoside, vicianin [mandelonitrile beta-vicianoside
      (6-O-alpha-L-arabinopyranosyl-beta-D-glucopyranoside)], is accumulated in seeds
      of Vicia angustifolia var. segetalis. Vicianin hydrolase (VH) catalyzes the
      hydrolysis of vicianin into mandelonitrile and a disaccharide vicianose. VH was
      purified from the seeds using DEAE-, CM- and Con A-Sepharose chromatography, and
      the molecular mass of the purified VH was estimated to be 56 kDa on SDS-PAGE. The
      N-terminal amino acid sequence of the purified VH was determined, and a cDNA
      encoding VH was obtained. The deduced VH protein consists of a 509 amino acid
      polypeptide containing a putative secretion signal peptide. It shares about 50%
      identity with various kinds of plant beta-glycosidases including tea leaf beta
      primeverosidase and furcatin hydrolase, and is classified in family 1 of the
      glycosyl hydrolases. The VH transcript was detected abundantly in seeds and
      moderately in flowers, but only slightly in leaves, stems and roots, indicating
      that the organ distribution of VH expression is similar to that of the substrate
      vicianin. The recombinant VH was produced in insect cells with a baculovirus
      system, and was compared with the native VH in terms of substrate specificity.
      Both enzymes hydrolyzed vicianin to release vicianose, demonstrating that VH is a
      disaccharide-specific beta-glycosidase. VH also hydrolyzed the mandelonitrile
      beta-glucoside prunasin to some extent but did not hydrolyze the gentiobioside
      amygdalin, both of which contain the same aglycone as vicianin. Thus, VH is a
      unique cyanogenic glycosidase showing high glycone specificity for the
      disaccharide vicianoside.

PMID- 17548374
TI  - Expression of the algal cytochrome c6 gene in Arabidopsis enhances photosynthesis
      and growth.
AB  - Photosynthetic plants convert light energy into ATP and NADPH in photosynthetic
      electron transfer and photophosphorylation, and synthesize mainly carbohydrates
      in the Calvin-Benson cycle. Here we report the enhancement of photosynthesis and
      growth of plants by introducing the gene of an algal cytochrome c6, which has
      been evolutionarily eliminated from higher plant chloroplasts, into the model
      plant Arabidopsis thaliana. At 60 d after planting, the plant height, leaf length
      and root length of the transformants were 1.3-, 1.1- and 1.3-fold those in the
      wild-type plants, respectively. At the same time, in the transgenic plants, the
      amounts of chlorophyll, protein, ATP, NADPH and starch were 1.2-, 1.1-, 1.9-, 1.4
      and 1.2-fold those in the wild-type plants, respectively. The CO2 assimilation
      capacity of the transgenic plants was 1.3-fold that of the wild type. Moreover,
      in transgenic Arabidopsis expressing algal cytochrome c6, the 1-qP, which
      reflects the reduced state of the plastoquinone pool, is 30% decreased compared
      with the wild type. These results show that the electron transfer of
      photosynthesis of Arabidopsis would be accelerated by the expression of algal
      cytochrome c6. Our results demonstrate that the growth and photosynthesis of
      Arabidopsis plants could be enhanced by the expression of the algal cytochrome c6
      gene.

PMID- 17548375
TI  - Clinical trial registration: looking back and moving ahead.

PMID- 17548376
TI  - Clinical trial registration: looking back and moving ahead.

PMID- 17548377
TI  - Protecting vaccine programs and the public.

PMID- 17548378
TI  - Sir Frederick Banting homestead sold to developer, family outraged.

PMID- 17548379
TI  - US children's study escapes knife.

PMID- 17548380
TI  - Northern Ontario medical school first to require community clerkships.

PMID- 17548381
TI  - The re-emergence in Canada of meningovascular syphilis: 2 patients with headache
      and stroke.

PMID- 17548382
TI  - Bilateral trapezius hypertrophy with dystonia and atrophy.

PMID- 17548384
TI  - Prevalence of methylphenidate use among Canadian children following parental
      divorce.
AB  - BACKGROUND: Evidence suggests that children living in single-parent or step
      parent households are more likely than children in households with 2 biological
      parents to be prescribed methylphenidate. I conducted a study of prospective data
      to investigate parental divorce as a predictor of methylphenidate use. METHODS: I
      used data for children who participated in the National Longitudinal Survey of
      Children and Youth from 1994 to 2000. The sample was restricted to children who
      remained in the survey in 2000 and who, at initial interview, lived in a
      household with 2 biological parents (n = 4784). A generalized estimating equation
      model was used to compare the odds ratios of methylphenidate use among children
      whose parents obtained a divorce between 1994 and 2000 relative to children whose
      parents remained married during this period. RESULTS: Between 1994 and 2000, 633
      children (13.2%) experienced the divorce of their parents. The proportion of
      children who received methylphenidate at any time between 1994 and 2000 was 3.3%
      among those whose parents remained married and 6.1% among those whose parents
      divorced during this period. After adjustment for age of the mother and sex and
      age of the child, I found that methylphenidate use was significantly higher among
      children whose parents subsequently divorced than among those whose parents
      remained married (odds ratio 1.82, 95% confidence interval 1.01-3.33).
      INTERPRETATION: The increased risk of children receiving a prescription for
      methylphenidate in the period following parental divorce raises questions about
      the causal links in this association. Future research is needed to replicate
      these findings and to investigate possible explanations.

PMID- 17548383
TI  - Impact of a pay-for-performance incentive on support for smoking cessation and on
      smoking prevalence among people with diabetes.
AB  - BACKGROUND: Many people with diabetes continue to smoke despite being at high
      risk of cardiovascular disease. We examined the impact of a pay-for-performance
      incentive in the United Kingdom introduced in 2004 as part of the new general
      practitioner contract to improve support for smoking cessation and to reduce the
      prevalence of smoking among people with chronic diseases such as diabetes.
      METHODS: We performed a population-based longitudinal study of the recorded
      delivery of cessation advice and the prevalence of smoking using electronic
      records of patients with diabetes obtained from participating general practices.
      The survey was carried out in an ethnically diverse part of southwest London
      before (June-October 2003) and after (November 2005-January 2006) the
      introduction of a pay-for-performance incentive. RESULTS: Significantly more
      patients with diabetes had their smoking status ever recorded in 2005 than in
      2003 (98.8% v. 90.0%, p <0.001). The proportion of patients with documented
      smoking cessation advice also increased significantly over this period, from
      48.0% to 83.5% (p < 0.001). The prevalence of smoking decreased significantly
      from 20.0% to 16.2% (p < 0.001). The reduction over the study period was lower
      among women (adjusted odds ratio 0.71, 95% confidence interval 0.53-0.95) but was
      not significantly different in the most and least affluent groups. In 2005,
      smoking rates continued to differ significantly with age (10.6%-25.1%), sex
      (women, 11.5%; men, 20.6%) and ethnic background (4.9%-24.9%). INTERPRETATION:
      The introduction of a pay-for-performance incentive in the United Kingdom
      increased the provision of support for smoking cessation and was associated with
      a reduction in smoking prevalence among patients with diabetes in primary health
      care settings. Health care planners in other countries may wish to consider
      introducing similar incentive schemes for primary care physicians.

PMID- 17548385
TI  - Pay for performance: learning about quality.

PMID- 17548386
TI  - Encouraging medical students to do research and write papers.

PMID- 17548387
TI  - Informed consent in embryonic stem cell research: are we following basic
      principles?

PMID- 17548388
TI  - The World Bank and sub-Saharan Africa's HIV/AIDS crisis.

PMID- 17548390
TI  - Industrial health research in Canada.

PMID- 17548391
TI  - Cardiovascular imaging techniques.

PMID- 17548392
TI  - Organ donation after cardiocirculatory death.

PMID- 17548393
TI  - Novice drivers with attention-deficit hyperactivity disorder.

PMID- 17548394
TI  - Noncompliance in randomized controlled trials.

PMID- 17548396
TI  - Staffing levels in long-term care facilities.

PMID- 17548398
TI  - Thyroid hormone therapy in organ donors.

PMID- 17548399
TI  - Hippocrates affirmed? Limiting residents' work hours does no harm to patients.

PMID- 17548400
TI  - Summaries for patients. Changes in outcomes for hospitalized patients after
      regulations to restrict resident doctors' work hours.

PMID- 17548401
TI  - Changes in outcomes for internal medicine inpatients after work-hour regulations.
AB  - BACKGROUND: Limits on resident work hours are intended to reduce fatigue-related
      errors, but may raise risk by increasing transfers of responsibility for
      patients. OBJECTIVE: To examine changes in outcomes for internal medicine
      patients after the implementation of work-hour regulations. DESIGN: Retrospective
      cohort study. SETTING: Urban, academic medical center. PATIENTS: 14,260
      consecutive patients discharged from the teaching (housestaff) service and 6664
      consecutive patients discharged from the nonteaching (hospitalist) service
      between 1 July 2002 and 30 June 2004. MEASUREMENTS: Outcomes included intensive
      care unit utilization, length of stay, discharge disposition, 30-day readmission
      rate to the study institution, pharmacist interventions to prevent error, drug
      drug interactions and in-hospital death. RESULTS: The teaching service had net
      improvements in 3 outcomes. Relative to changes experienced by the nonteaching
      service, the rate of intensive care unit utilization decreased by 2.1% (95% CI, 
      3.3% to -0.7%; P = 0.002), the rate of discharge to home or rehabilitation
      facility versus elsewhere improved by 5.3% (CI, 2.6% to 7.6%; P < 0.001), and
      pharmacist interventions to prevent error were reduced by 1.92 interventions per
      100 patient-days (CI, -2.74 to -1.03 interventions per 100 patient-days; P <
      0.001). Teaching and nonteaching services had similar changes over time in length
      of stay, 30-day readmission rate, and adverse drug-drug interactions. In-hospital
      death was uncommon in both groups, and change over time was similar in the 2
      groups. LIMITATIONS: The study was a retrospective, nonrandomized design that
      assessed a limited number of outcomes. Teaching and nonteaching cohorts may not
      have been affected similarly by secular trends in patient care. CONCLUSIONS:
      After the implementation of work-hour regulations, 3 of 7 outcomes improved for
      patients in the teaching service relative to those in the nonteaching service.
      The authors found no evidence of adverse unintended consequences after the
      institution of work-hour regulations.

PMID- 17548402
TI  - Summaries for patients. Changes in hospital mortality after regulations to
      restrict resident doctors' work hours.

PMID- 17548403
TI  - Changes in hospital mortality associated with residency work-hour regulations.
AB  - BACKGROUND: In 2002, the Accreditation Council on Graduate Medical Education
      enacted regulations, effective 1 July 2003, that limited work hours for all
      residency programs in the United States. OBJECTIVE: To determine whether work
      hour regulations were associated with changes in mortality in hospitalized
      patients. DESIGN: Comparison of mortality rates in high-risk teaching service
      patients hospitalized before and after July 2003, with nonteaching service
      patients used as a control group. SETTING: 551 U.S. community hospitals included
      in the Healthcare Cost and Utilization Project's Nationwide Inpatient Survey
      between January 2001 and December 2004. PATIENTS: 1,511,945 adult patients
      admitted for 20 medical and 15 surgical diagnoses. MEASUREMENT: Inpatient
      mortality. RESULTS: In 1,268,738 medical patients examined, the regulations were
      associated with a 0.25% reduction in the absolute mortality rate (P = 0.043) and
      a 3.75% reduction in the relative risk for death. In subgroup analyses,
      particularly large improvements in mortality were observed among patients
      admitted for infectious diseases (change, -0.66%; P = 0.007) and in medical
      patients older than 80 years of age (change, -0.71%; P = 0.005). By contrast, in
      243,207 surgical patients, regulations were not associated with statistically
      significant changes (change, 0.13%; P = 0.54). LIMITATIONS: Teaching status was
      assigned according to hospital characteristics because direct information on each
      patient's provider was not available. Results reflect changes associated with the
      sum of regulations, not specifically with caps on work hours. CONCLUSIONS: The
      work-hour regulations were associated with decreased short-term mortality among
      high-risk medical patients in teaching hospitals but were not associated with
      statistically significant changes among surgical patients in teaching hospitals.

PMID- 17548404
TI  - Clinical trial registration: looking back and moving ahead.

PMID- 17548405
TI  - Summaries for patients. Antipsychotic drug use and death in older adults with
      dementia.

PMID- 17548406
TI  - Summaries for patients. Physiotherapist-directed exercise, advice, or both for
      low back pain.

PMID- 17548407
TI  - In the clinic. Asthma.

PMID- 17548408
TI  - Changes in health care expenditure associated with gaining or losing health
      insurance.
AB  - BACKGROUND: Cross-sectional data suggest that changes in health insurance status
      are associated with expenditures. No national longitudinal analysis has examined
      this relationship. OBJECTIVE: To evaluate the association between changes in
      health insurance status and expenditures. DESIGN: Cohort analyses using the 2000
      to 2003 Medical Expenditure Panel Surveys. SETTING: U.S. civilian
      noninstitutionalized population. PARTICIPANTS: Three 2-year cohorts that included
      20,848 adults age 21 to 64 years who were stratified by insurance type (private,
      public, military, or none): 17,130 participants were insured in both years, 342
      participants were insured in year 1 and were uninsured in year 2, 385
      participants were uninsured in year 1 and were insured in year 2, and 2991
      participants were uninsured in both years. Persons who were insured for longer
      than 2 months but less than 10 months or who switched insurance type were
      excluded (n = 4039). MEASUREMENTS: Annual health care expenditures (any or none;
      amount, contingent on any expenditure; and the difference between year 1 and year
      2). RESULTS: Adjusted expenditure probabilities were similar among all
      participant groups while insured and were higher than those for all participant
      groups while uninsured: 92.1% (95% CI, 91.4% to 92.7%) in year 1 and 91.8% (CI,
      90.9% to 92.5%) in year 2 for persons insured in both years, 74.2% (CI, 71.7% to
      76.5%) in year 1 and 74.8% (CI, 72.1% to 77.4%) in year 2 for persons uninsured
      in both years, and 90.7% (CI, 87.1% to 93.4%) for persons insured in year 1 and
      74.6% (CI, 69.4% to 79.2%) for persons uninsured in year 2. The pattern was also
      consistent for the group that was uninsured in year 1 but insured in year 2.
      Adjusted annual expenditures among all participant groups with insurance were
      similar; expenditures among participant groups without insurance were similar but
      were lower than those among participants with insurance. Consistent differences
      in expenditures between year 1 and year 2 were observed for all groups.
      LIMITATION: Few participants changed insurance status. CONCLUSION: Changing
      insurance status is associated with changes in expenditures to levels that are
      similar to those for persons who are continuously insured or uninsured.

PMID- 17548409
TI  - Antipsychotic drug use and mortality in older adults with dementia.
AB  - BACKGROUND: Antipsychotic drugs are widely used to manage behavioral and
      psychological symptoms in dementia despite concerns about their safety.
      OBJECTIVE: To examine the association between treatment with antipsychotics (both
      conventional and atypical) and all-cause mortality. DESIGN: Population-based,
      retrospective cohort study. SETTING: Ontario, Canada. PATIENTS: Older adults with
      dementia who were followed between 1 April 1997 and 31 March 2003. MEASUREMENTS:
      The risk for death was determined at 30, 60, 120, and 180 days after the initial
      dispensing of antipsychotic medication. Two pairwise comparisons were made:
      atypical versus no antipsychotic use and conventional versus atypical
      antipsychotic use. Groups were stratified by place of residence (community or
      long-term care). Propensity score matching was used to adjust for differences in
      baseline health status. RESULTS: A total of 27,259 matched pairs were identified.
      New use of atypical antipsychotics was associated with a statistically
      significant increase in the risk for death at 30 days compared with nonuse in
      both the community-dwelling cohort (adjusted hazard ratio, 1.31 [95% CI, 1.02 to
      1.70]; absolute risk difference, 0.2 percentage point) and the long-term care
      cohort (adjusted hazard ratio, 1.55 [CI, 1.15 to 2.07]; absolute risk difference,
      1.2 percentage points). Excess risk seemed to persist to 180 days, but unequal
      rates of censoring over time may have affected these results. Relative to
      atypical antipsychotic use, conventional antipsychotic use was associated with a
      higher risk for death at all time points. Sensitivity analysis revealed that
      unmeasured confounders that increase the risk for death could diminish or
      eliminate the observed associations. LIMITATIONS: Information on causes of death
      was not available. Many patients did not continue their initial treatments after
      1 month of therapy. Unmeasured confounders could affect associations.
      CONCLUSIONS: Atypical antipsychotic use is associated with an increased risk for
      death compared with nonuse among older adults with dementia. The risk for death
      may be greater with conventional antipsychotics than with atypical
      antipsychotics.

PMID- 17548410
TI  - Physiotherapist-directed exercise, advice, or both for subacute low back pain: a
      randomized trial.
AB  - BACKGROUND: Advice and exercise are widely recommended for subacute low back
      pain, but the effectiveness of these interventions is unclear. OBJECTIVE: To
      investigate the effectiveness of physiotherapist-prescribed exercise, advice, or
      both for subacute low back pain. DESIGN: Factorial randomized, placebo-controlled
      trial. SETTING: 7 university hospitals and primary care clinics in Australia and
      New Zealand. PATIENTS: 259 persons with subacute low back pain (>6 weeks and <3
      months in duration). INTERVENTION: Participants received 12 physiotherapist
      directed exercise or sham exercise sessions and 3 physiotherapist-directed advice
      or sham advice sessions over 6 weeks. MEASUREMENTS: Primary outcomes were average
      pain over the past week (scale, 0 to 10), function (Patient-Specific Functional
      Scale), and global perceived effect (11-point scale) at 6 weeks and 12 months.
      Secondary outcomes were disability (Roland-Morris Disability Questionnaire),
      number of health care contacts, and depression (Depression Anxiety Stress Scales
      21). RESULTS: Exercise and advice were each slightly more effective than placebo
      at 6 weeks but not at 12 months. The effect of advice on the pain scale was -0.7
      point (95% CI, -1.2 to -0.2 point; P = 0.011) at 6 weeks and -0.4 point (CI, -1.0
      to 0.3 point; P = 0.27) at 12 months, whereras the effect of exercise was -0.8
      point (CI, -1.3 to -0.3 point; P = 0.004) at 6 weeks and -0.5 point (CI, -1.1 to
      0.2 point; P = 0.14) at 12 months. The effect of advice on the function scale was
      0.7 point (CI, 0.1 to 1.3 points; P = 0.014) at 6 weeks and 0.6 point (CI, 0.1 to
      1.2 points; P = 0.023) at 12 months, and the effect of exercise was 0.4 point
      (CI, -0.2 to 1.0 point; P = 0.174) at 6 weeks and 0.5 point (CI, -0.1 to 1.0
      point; P = 0.094) at 12 months. The effect of advice on the global perceived
      effect scale was 0.8 point (CI, 0.3 to 1.2 points; P < 0.001) at 6 weeks and 0.3
      point (CI, -0.2 to 0.9 point; P = 0.24) at 12 months, and the effect of exercise
      was 0.5 point (CI, 0.1 to 1.0 point; P = 0.017) at 6 weeks and 0.4 point (CI, 
      0.1 to 1.0 point; P = 0.134) at 12 months. When administered together, exercise
      and advice had larger effects on all outcomes at 6 weeks (effect on pain, -1.5
      [CI -2.2 to -0.7 point; P = 0.001], with similar results for other primary
      outcomes); however, by 12 months, there was a statistically significant effect
      only for function (effect, 1.1 points [CI, 0.3 to 1.8 points]; P = 0.005).
      LIMITATION: Physiotherapists were not blinded. CONCLUSIONS: In participants with
      subacute low back pain, physiotherapist-directed exercise and advice were each
      slightly more effective than placebo at 6 weeks. The effect was greatest when the
      interventions were combined. At 12 months, the only effect that persisted was a
      small effect on participant-reported function. AUSTRALIAN CLINICAL TRIALS
      REGISTRY REGISTRATION NUMBER: 12605000039684.

PMID- 17548411
TI  - Meta-analysis: diagnostic accuracy of anti-cyclic citrullinated peptide antibody
      and rheumatoid factor for rheumatoid arthritis.
AB  - BACKGROUND: Rheumatoid factor (RF) and autoantibodies against cyclic
      citrullinated peptide (CCP) are markers that might help physicians diagnose
      rheumatoid arthritis. PURPOSE: To determine whether anti-CCP antibody more
      accurately identifies patients with rheumatoid arthritis and better predicts
      radiographic progression than does RF. DATA SOURCES: MEDLINE through September
      2006 and reference lists of retrieved studies and review articles. STUDY
      SELECTION: Studies in any language that enrolled at least 10 participants and
      that examined the role of anti-CCP antibody and RF in the diagnosis or prognosis
      of known or suspected rheumatoid arthritis. DATA EXTRACTION: Two authors
      independently evaluated studies for inclusion, rated methodological quality, and
      abstracted relevant data. DATA SYNTHESIS: The DerSimonian-Laird random-effects
      method was used to summarize sensitivities, specificities, and positive and
      negative likelihood ratios from 37 studies of anti-CCP antibody and 50 studies of
      RF. The pooled sensitivity, specificity, and positive and negative likelihood
      ratios for anti-CCP antibody were 67% (95% CI, 62% to 72%), 95% (CI, 94% to 97%),
      12.46 (CI, 9.72 to 15.98), and 0.36 (CI, 0.31 to 0.42), respectively. For IgM RF,
      the values were 69% (CI, 65% to 73%), 85% (CI, 82% to 88%), 4.86 (CI, 3.95 to
      5.97), and 0.38 (CI, 0.33 to 0.44). Likelihood ratios among IgM RF, IgG RF, and
      IgA RF seemed to be similar. Results from studies of patients with early
      rheumatoid arthritis were similar to those from all studies. Three of 4 studies
      found that risk for radiographic progression was greater with anti-CCP antibody
      positivity than with IgM RF positivity. LIMITATIONS: Many studies had
      methodological limitations. Studies of RF were heterogeneous and had wide ranges
      of sensitivity and specificity. CONCLUSIONS: Anti-CCP antibodies are more
      specific than RF for diagnosing rheumatoid arthritis and may better predict
      erosivedisease.

PMID- 17548412
TI  - Lessons in medical humanism: the case of Montaigne.
AB  - Michel de Montaigne, the great French humanist and inventor of the personal
      essay, suffered from frequent and severe renal colic. He wrote about his illness
      in his travel journal and in his last and greatest essay, "Of Experience." In his
      illness narratives, Montaigne integrated disease and suffering into his life and
      art. He humanized rather than conquered his disease. A mature humanism replaced
      his youthful Stoic philosophy of detachment and disengagement and provides a
      worthy model for our own medical humanism.

PMID- 17548413
TI  - Insurance and health care expenditures: what's the real question?

PMID- 17548414
TI  - Anti-cyclic citrullinated peptide antibodies in the diagnosis of rheumatoid
      arthritis: bayes clears the haze.

PMID- 17548415
TI  - David Miller.

PMID- 17548416
TI  - Colorectal screening after polypectomy.

PMID- 17548417
TI  - Colorectal screening after polypectomy.

PMID- 17548418
TI  - Effect of inhaled insulin on fasting and postprandial plasma glucose.

PMID- 17548419
TI  - Pay-for-performance and accountability.

PMID- 17548420
TI  - Pay-for-performance and accountability.

PMID- 17548421
TI  - Pay-for-performance and accountability.

PMID- 17548422
TI  - Pay-for-performance and accountability.

PMID- 17548423
TI  - Treatment of familial Mediterranean fever with anakinra.

PMID- 17548424
TI  - Epstein-Barr virus-associated cholecystitis.

PMID- 17548425
TI  - Socio-demographic variations in moves to institutional care 1991-2001: a record
      linkage study from England and Wales.
AB  - BACKGROUND: Only a minority of older people in England and Wales live in
      institutional care, but among the older of the old, this minority is large.
      Disability is the major driver of admissions, but socio-demographic factors are
      also relevant. Understanding more about the influence of these is important for
      planning by long-term care. OBJECTIVE: To investigate effects of socio
      demographic factors, including housing tenure, household type, marital status,
      and number of children, on the proportions of elderly people who made a
      transition from living in the community in 1991 to living in institutional care
      in 2001. SUBJECTS AND SETTING: Nationally representative record linkage study
      including 36,650 people aged 65 years and over, living in the community in
      England and Wales in 1991, who were still alive in 2001. Nineteen thousand women
      aged 75-89 years in 2001 were included in additional analyses of effects of
      parity (number of children borne). METHODS: Bi-variate and multivariate analyses
      of variations in sample proportions, who by 2001 were resident in institutional
      care. RESULTS: 4.3% of men and 9.3% of women in the surviving sample then aged 75
      years and over, were in institutional care in 2001. Older age, living in rented
      accommodation, living alone in 1991 and being unmarried in 2001, as well as long
      term illness, were associated with higher proportions making this transition.
      Women had higher risks than men. Childless women aged 64-79 years in 1991 had a
      25% higher risk than women with children of being in institutional care in 2001.
      CONCLUSION: Socio-demographic factors continue to influence risks of entry to
      institutional care in England and Wales.

PMID- 17548426
TI  - Post-stroke dysphagia and long-term outcome: baseline assessments of cortical
      dysfunction need to be clearer.

PMID- 17548427
TI  - Clinical trial registration--looking back and moving ahead.

PMID- 17548428
TI  - Mechanisms of ceramide-mediated repression of the human telomerase reverse
      transcriptase promoter via deacetylation of Sp3 by histone deacetylase 1.
AB  - In this study, distinct roles of de novo-generated endogenous ceramides and
      mechanisms by which deacetylated Sp3 regulates the hTERT promoter activity in
      response to ceramide signaling were explored. The generation of C18-ceramide via
      the expression of ceramide synthase 1 (CerS1), and not C16-ceramide by CerS5 or
      CerS6 expression, resulted in repression of the hTERT promoter via deacetylation
      of Sp3 by histone deacetylase 1 (HDAC1) in A549 human lung adenocarcinoma cells.
      Then roles and mechanisms of action of ceramide-mediated deacetylation of Sp3 in
      inhibiting the hTERT promoter were determined using constitutively deacetylated
      or acetylated Sp3 mutants at lysine (K) 551. Expression of the deacetylated Sp3
      mutant resulted in repression, whereas its acetylated mutant induced basal hTERT
      promoter activity in Drosophila S2 cells, which do not express any endogenous
      Sp3, and in A549 cells. Remarkably, chromatin immunoprecipitation data revealed
      that acetylated Sp3 mutant (K551Q-Sp3) did not bind whereas deacetylated Sp3
      (K551R-Sp3) mutant bound strongly to the promoter DNA, resulting in the
      recruitment of histone deacetylase 1 (HDAC1) and inhibition of the association of
      RNA polymerase II with the promoter. Mechanistically, increased generation of C18
      ceramide by hCerS1 expression, but not by its catalytically inactive mutant,
      mediated the association and recruitment of the deacetylated Sp3/HDAC1 complex to
      the hTERT promoter DNA, resulting in the local histone H3 deacetylation and
      repression of the promoter.

PMID- 17548430
TI  - Effects of cardiopulmonary bypass on neurocognitive performance and cytokine
      release in old and diabetic rats.
AB  - BACKGROUND: Age and diabetes mellitus have been identified as independent risk
      factors for cognitive decline after cardiac surgery with cardiopulmonary bypass
      (CPB). We tested the effects of CPB on cognitive function in aged and diabetic
      rats utilizing the Morris water maze (MWM). METHODS: Aged rats (26 months) were
      randomized into a sham group (cannulation but no CPB, n = 11) and a 90 min CPB
      group (n = 11). In addition, young rats (n = 14) were made diabetic with
      streptozotocin 9 weeks before experimentation and randomized to a sham or 90 min
      CPB group. Cytokine release [interleukin (IL-6)] and short-term MWM performance
      (days 8-14 after operation) were assessed in all animals. Long-term MWM
      performance (8 weeks after operation) was assessed in aged rats only. RESULTS:
      There were no differences between the aged groups in short-term (P = 0.58) or
      long-term MWM performances (P = 0.69). The diabetic animals also showed no
      differences between the sham and CPB groups in MWM performance (P = 0.64). IL-6
      assays showed an increased inflammatory response after CPB in the diabetic
      animals, but not in the elderly groups. CONCLUSIONS: Ninety minutes of
      normothermic CPB had no deleterious effect on neurocognitive outcome in elderly
      or chronically diabetic animals, suggesting that CPB in itself is not a
      sufficient stressor of the rat central nervous system.

PMID- 17548429
TI  - Duplicated gelsolin family genes in zebrafish: a novel scinderin-like gene
      (scinla) encodes the major corneal crystallin.
AB  - We have previously identified a gelsolin-like protein (C/L-gelsolin) as a corneal
      crystallin in zebrafish. Here we show by phylogenetic analysis that there are at
      least six genes encoding gelsolin-like proteins based on their gelsolin domains
      in zebrafish: gsna and gsnb group with the vertebrate gelsolin gene, scina and
      scinb group with the scinderin (adseverin) gene, and scinla (C/L-gelsolin) and
      scinlb are novel scinderin-like genes. RT-PCR showed that scinla, scinlb, and
      gsnb are preferentially expressed in the adult cornea whereas gsna is expressed
      to a similar extent in cornea, lens, brain, and heart; scina and scinb expression
      were detectable only in whole zebrafish and not in these adult tissues.
      Quantitative RT-PCR and 2-dimensional polyacrylamide gel electrophoresis followed
      by MALDI/TOF mass spectroscopy confirmed high expression of beta-actin and
      scinla, moderate expression of scinlb, and very low expression of gsna and gsnb
      in the cornea. Finally, transgenic zebrafish carrying a green fluorescent protein
      reporter transgene driven by a 4 kb scinla promoter fragment showed expression in
      the cornea, snout, dorsal fin, and tail fin of 3-day-old zebrafish larvae. Our
      data suggest that scinla and scinlb are diverged paralogs of the vertebrate
      scinderin gene and show that scinla encodes the zebrafish corneal crystallin
      previously called C/L-gelsolin.

PMID- 17548431
TI  - Multimodal monitoring in traumatic brain injury: current status and future
      directions.
AB  - Traumatic brain injury (TBI) remains a major cause of morbidity and mortality,
      particularly in young people. Despite encouraging animal studies, human trials
      assessing the use of pharmacological agents after TBI have all failed to show
      efficacy. Current management strategies are therefore directed towards providing
      an optimal physiological environment in order to minimize secondary insults and
      maximize the body's own regenerative processes. Modern neurocritical care
      management utilizes a host of monitoring techniques to identify or predict the
      occurrence of secondary insults and guide subsequent therapeutic interventions in
      an attempt to minimize the resulting secondary injury. Recent data suggest that
      the use of protocolized management strategies, informed by multimodality
      monitoring, can improve patient outcome after TBI. Developments in multimodality
      monitoring have allowed a movement away from rigid physiological target setting
      towards an individually tailored, patient-specific, approach. The wealth of
      monitoring information available provides a challenge in terms of data
      integration and accessibility and modern software applications may aid this
      process.

PMID- 17548432
TI  - Improved native affinity purification of RNA.
AB  - RNA biochemical or structural studies often require an RNA sample that is
      chemically pure, and most protocols for its in vitro production use denaturing
      polyacrylamide gel electrophoresis to achieve this. Unfortunately, many RNAs do
      not quantitatively refold into an active conformation after denaturation,
      creating significant problems for downstream characterization or use. In
      addition, this traditional purification method is not amenable to studies
      demanding high-throughput RNA production. Recently, we presented the first
      general method for producing almost any RNA sequence that employs an affinity tag
      that is removed during the purification process. Because technical difficulties
      prevented application of this method to many RNAs, we have developed an improved
      version that utilizes a different activatable ribozyme and affinity tag that are
      considerably more robust, rapid, and broadly applicable.

PMID- 17548434
TI  - Measuring and management of anti-interferon beta antibodies in subjects with
      multiple sclerosis.
AB  - Interferon Beta is well established as a first line agent to treat relapsing
      remitting Multiple Sclerosis. It frequently induces the formation of neutralising
      anti-Interferon Beta Antibodies (Nabs) which may abrogate the clinical efficacy
      of the drug. Numerous studies have shown a loss of bioactivity of the drug in the
      presence of Nabs. The focus has shifted to reliable quantification of Nabs and
      their appropriate incorporation into clinical practice. Here we review the
      development and persistence of Nabs, the effect on Interferon beta bioactivity,
      clinical and para-clinical autocome measures in trials, Nab assays and discuss
      management strategies to optimise the use of Interferon beta in relapsing
      remitting MS.

PMID- 17548433
TI  - hnRNP I/PTB can antagonize the splicing repressor activity of SRp30c.
AB  - The control of alternative pre-mRNA splicing often requires the participation of
      factors displaying synergistic or antagonistic activities. In the hnRNP A1 pre
      mRNA, three elements promote the exclusion of alternative exon 7B, while a fourth
      intron element (CE9) represses splicing of exon 7B to the downstream exon. We
      have shown previously that the 5' portion of the 38-nucleotide-long CE9 element
      is bound by SRp30c, and that this interaction is important for repression in
      vitro. To determine whether SRp30c alone can impose repression, we tested a high
      affinity SRp30c binding site that we identified using the SELEX protocol. We find
      that multiple high-affinity SRp30c sites are required to replicate the level of
      repression obtained with CE9, and that both the 5' and the 3' portions of CE9
      contribute to SRp30c binding. Performing RNA affinity chromatography with the
      complete CE9 element recovered hnRNP I/PTB. Surprisingly however, His-tagged PTB
      reduced the binding of SRp30c to CE9 in a nuclear extract, stimulated splicing to
      a downstream 3' splice site, and relieved the CE9-mediated splicing repression in
      vitro. Our in vivo results are consistent with the notion that increasing PTB
      levels alleviates the repression imposed by CE9 to a downstream 3' splice site.
      Thus, PTB can function as an anti-repressor molecule to counteract the splicing
      inhibitory activity of SRp30c.

PMID- 17548435
TI  - Human herpesvirus-6 and multiple sclerosis: relapsing-remitting versus secondary
      progressive.
AB  - Recently, it has been suggested that human herpesvirus-6 (HHV-6) may play a role
      in the pathogenesis of relapsing-remitting multiple sclerosis (RRMS), but there
      is not enough information related to the role of HHV-6 in secondary-progressive
      MS (SPMS). To address this question, we evaluated HHV-6 prevalence, active viral
      replication and viral load measured by quantitative real-time PCR, in DNA and
      mRNA extracted from peripheral blood mononuclear cells (PBMCs) and DNA extracted
      from serum; the samples were collected from 31 SPMS and 31 RRMS patients in a one
      year follow-up study, and sex- and age-matched controls. The results were as
      follows: i) We found a statistical significant difference in HHV-6 DNA
      prevalences between RRMS and SPMS patients in: DNA extracted from PBMCs
      (P=0.027), DNA extracted from serum (P=0.010) and mRNA extracted from PBMCs
      (P=0.010). When we compared HHV-6 prevalences from RRMS patients in relapse and
      in remission with those from SPMS patients, we only achieved a statistical
      significance for the relapses (P=0.003 in DNA from PBMCs, and P<0.001 in DNA from
      serum samples and mRNA from PBMCs). ii) We only found HHV-6 variant A among HHV-6
      positive samples in serum. iii) We did not find any difference in HHV-6 viral
      loads. These results suggest that HHV-6A does not play an active role in SPMS,
      while this virus may contribute to the pathogenesis of RRMS triggering MS attacks
      in a subset of patients.

PMID- 17548436
TI  - A follow-up study of Nordic multiple sclerosis candidate gene regions.
AB  - In this study, the results from three Nordic linkage disequilibrium screens in
      multiple sclerosis (MS) were investigated, in a new sample set of 314 Nordic MS
      trios from Denmark, Norway, Sweden and Iceland. Among 30 non-HLA and two HLA
      microsatellite markers individually genotyped, eight markers displayed distorted
      transmission with uncorrected P-value<0.05, ranked in this order: D6S2443
      (6p21.32, HLA class II) (P corrected=0.01), D2S2201 (2p24), D19S552 (19q13),
      D3S3584 (3q21), D17S975 (17q11), D1S2627 (1p22), D6S273 (6p21.33, HLA class III)
      and D12S1051 (12q23). These non-HLA regions need further investigation as
      possible MS candidate gene regions in our population.

PMID- 17548437
TI  - JC virus in cerebrospinal fluid samples of multiple sclerosis patients at the
      first demyelinating event.
AB  - OBJECTIVE: To evaluate the possible involvement of JC virus (JCV) in the
      aetiology of multiple sclerosis (MS), through the comparison of DNA prevalences
      and viral loads of JCV in cerebrospinal fluid (CSF) of MS patients at the first
      demyelinating event and subjects suffering from other neurological diseases
      (OND). METHODS: Seventy-three CSF samples (43 from MS patients at the first
      demyelinating event, and 30 from patients with OND) were collected; all MS cases
      were followed up from 1 to 6.7 years after they were diagnosed with clinically
      definite MS. DNA was extracted and analysed by real-time PCR for the detection of
      JCV genomes. RESULTS: We found JCV DNA in the CSF of two MS patients (4.7%) with
      a mean viral load of 2.1 and 6.7 copies/mL of CSF. Among the patients of the OND
      group we did not find any positive sample. We did not find any difference in the
      course of the disease between MS patients with and without JCV genomes in their
      CSF along the follow up. CONCLUSION: JCV seems to be only a bystander in the
      pathology of MS, and the presence of cell-free viral particles could be related
      to the immunological activation of the disease, mainly during relapses.

PMID- 17548438
TI  - Synergy between paclitaxel plus an exogenous methyl donor in the suppression of
      murine demyelinating diseases.
AB  - Progressive demyelination in multiple sclerosis (MS) reflects the negative
      balance between myelin damage and repair due to physical and molecular barriers,
      such as astrocytic glial scars, between oligodendrocytes and target neurons. In
      this paper, we show that combination therapy with paclitaxel (Taxol) plus the
      universal methyl-donor, vitamin B12CN (B12CN), dramatically limits progressive
      demyelination, and enhances remyelination in several independent, immune and
      nonimmune, in vivo and in vitro model systems. Combination therapy significantly
      reduced clinical signs of EAE in SJL mice, as well as the spontaneously
      demyelinating ND4 transgenic mouse. Astrocytosis was normalised in parallel to
      ultrastructural and biochemical evidence of remyelination. The combination
      therapy suppressed T cell expansion, reduced IFN-gamma, while enhancing IFN-beta
      and STAT-1 expression, STAT-1 phosphorylation and methylation of STAT-1 and MBP
      in the brain. Paclitaxel/B12CN has nearly identical effects to the previously
      described combination of IFN-beta/ B12CN, whose clinical usefulness is transient
      because of IFN-neutralising antibodies, not observed (or expected) with the
      present drug combination. This report provides a mechanistic foundation for the
      development of a new therapeutic strategy in humans with MS.

PMID- 17548439
TI  - Smoking is a risk factor for multiple sclerosis: a metanalysis.
AB  - Several case control studies have probed a link between cigarette smoking and
      subsequent multiple sclerosis (MS). Data collection and statistical methods have
      varied, and frequently, case numbers have been small. Publications relating to MS
      and smoking are reviewed and combined where comparable methods have been used.
      Metanalysis of six informative studies show significantly elevated odds or rate
      ratios, ranging from 1.22 to 1.51, depending on the method of analysis,
      confirming that the risk of MS is increased for those who smoke prior to disease
      onset, as measured by commencement of symptoms. A variety of direct causative
      mechanisms are discussed, but an indirect association through health adverse
      conduct is favoured.

PMID- 17548440
TI  - Are ex vivo neutralising antibodies against IFN-beta always detrimental to
      therapeutic efficacy in multiple sclerosis?
AB  - Neutralising antibodies (NAbs) against interferon (IFN)-beta reduce the treatment
      effect in multiple sclerosis (MS). However, data from pivotal trials of IFN-beta
      in MS suggest that NAb-positive patients may have a reduced relapse rate during
      the first six to 12 months of therapy. We collected clinical data and plasma
      samples for NAb measurements prospectively, every six months, in 468 patients
      treated with the same IFN-beta preparation for at least 24 months. NAbs were
      measured blindly with a cytopathic effect (CPE) assay. During treatment months 0
      6, patients who became NAb-positive had significantly fewer relapses compared to
      patients who maintained the NAb-negative status, whereas the opposite was
      observed after month 6. This is in accordance with observations in randomised
      studies of the three different IFN-beta preparations, showing that patients who
      become NAb-positive have lower relapse rates during the first six or 12 months of
      therapy. We hypothesise that low affinity NAbs, present early after the start of
      IFN-beta therapy, though neutralising in vitro in sensitive assays increase the
      half-life of IFN-beta in vivo and, thereby, enhance the therapeutic effect. With
      affinity maturation, NAbs effectively prevent IFN-beta binding to its receptors
      also in vivo and, hence, abolish the treatment effect.

PMID- 17548441
TI  - Primary progressive multiple sclerosis: a comparative study of the diagnostic
      criteria.
AB  - We assessed the different sets of diagnostic criteria for primary progressive
      multiple sclerosis (PPMS), in order to determine their sensitivity when applied
      to a cohort of 261 PPMS patients. According to the Thompson criteria, 168
      patients (64.4%) had definite PPMS, 84 patients (32.2%) had probable PPMS, and
      nine patients (3.4%) had possible PPMS; according to the McDonald criteria, 180
      patients (69%) had PPMS; according to the revised McDonald criteria, 194 patients
      (74.3%) had PPMS. Our findings indicate that the revised McDonald criteria are
      more sensitive than the original McDonald criteria, but less sensitive than the
      Thompson criteria.

PMID- 17548442
TI  - Clinical follow-up of 304 patients with multiple sclerosis three years after
      mitoxantrone treatment.
AB  - The objectives of this study were to assess the benefits of 1) mitoxantrone after
      three years of follow-up and 2) disease-modifying treatment (DMT) after stopping
      mitoxantrone. A retrospective analysis was performed on 304 patients with active
      relapsing-remitting (RR) or progressive multiple sclerosis (PMS) who were treated
      with mitoxantrone. After mitoxantrone therapy, some patients received DMT
      (interferon-beta or glatiramer acetate) while others did not. The disease course
      of the two groups was evaluated by the Expanded Disability Status Scale (EDSS)
      before and after mitoxantrone and then every year for three years. The mean EDSS
      score at starting mitoxantrone and three years after stopping mitoxantrone
      respectively, were: 3.3 (1.3) and 3.2 (1.7) for the RRMS patients and 5.9 (1.2)
      and 6.4 (1.4) for the PMS patients. Before starting mitoxantrone, demographic and
      clinical parameters of predictive disability were not significantly different
      between patients who received DMT or not. The variation of EDSS between time of
      stopping mitoxantrone and three years later was significantly different (+0.9
      versus +0.3; P=0.03) for patients with RRMS. We found that mitoxantrone treatment
      induces stable disease up to two years after discontinuation of mitoxantrone
      therapy. In the third year, patients without DMT deteriorated.

PMID- 17548443
TI  - Treatment of depression in people who have multiple sclerosis.
AB  - Depression is common among people with multiple sclerosis (MS). Research suggests
      that treatments for depression are effective in this population, though few
      patients appear to access these treatments. Our objectives were to consider
      whether persons with MS and significant depressive symptoms, prompted to seek
      treatment by letter, did so, what professionals they consulted, and the benefits
      of any treatment obtained. A total of 495 individuals with MS (401 female; 94
      male), aged 22-65 years (mean: 45.8 years), were surveyed in three phases at
      yearly intervals. Significant depressive symptoms were found over the three
      phases (50-60.2%). Despite a high prevalence of depressive symptoms, few
      participants sought treatment, even though prompted to do so. Where treatment was
      sought, general practitioners remained the principal group consulted. Contrary to
      previous reports of the efficacy of treatment in clinical trials, no strong
      support for this was found. Future research needs to consider why the majority of
      people with MS do not seek treatment for depression, and why interventions, which
      are not clinical trials, seem to lack effectiveness.

PMID- 17548444
TI  - The relationship between neuropsychological measures and the Timed Instrumental
      Activities of Daily Living task in multiple sclerosis.
AB  - Multiple sclerosis (MS) can result in cognitive deficits and a loss of functional
      independence. To date, little research has linked the observed cognitive and
      behavioral deficits in MS, especially those in the processing speed domain, to
      performance on tasks of everyday functioning. The present study examined the
      relationship between neuropsychological test performance and performance on the
      Timed Instrumental Activities of Daily Living task (TIADL) in individuals with
      MS, and in healthy controls (HCs). The TIADL is a functional measure, which
      assesses both accuracy and speed in one's performance of everyday activities. The
      MS group performed significantly worse on the TIADL relative to the HC group.
      Additionally, TIADL scores of individuals with MS were significantly correlated
      with neuropsychological measures of processing speed. TIADL scores were not,
      however, correlated with neuropsychological measures of verbal episodic memory or
      working memory. These results indicate that the impairments in processing speed
      may contribute to impairments in activities of everyday living in persons with
      MS.

PMID- 17548445
TI  - Impact of fatigue in multiple sclerosis: the Fatigue Impact Scale for Daily Use
      (D-FIS).
AB  - OBJECTIVE: The Fatigue Impact Scale for Daily Use (D-FIS) is an eight-item
      instrument designed to measure subjective daily experience of fatigue. This study
      sought to determine the metric properties of the D-FIS in multiple sclerosis (MS)
      patients. METHODS: Sixty-eight patients with operationally-defined MS and fatigue
      (54.8% of the sample) underwent the D-FIS. Usual clinical measures for MS, the
      Montgomery-Asberg Depression Rating Scale (MADRS) and the Functional Assessment
      of Multiple Sclerosis (FAMS) were also applied. In addition, patients with
      fatigue completed the Fatigue Descriptive Scale, the Multidimensional Fatigue
      Inventory (MFI), a Visual Analogue Scale for Fatigue (VAS-F), and a Global
      Perception of Fatigue Scale (GPF). RESULTS: Full computable data, 95.6%; both
      floor and ceiling effect=1.54%; item-total correlation=0.62 (item 1) to 0.84
      (item 6); Cronbach's alpha=0.91; item homogeneity =0.55; standard error of
      measurement=3.18; convergent validity with other fatigue measures=-0.57 (VAS-F);
      0.52 (GPF); and 0.46 (MFI-general fatigue). Test-retest reliability (ICC)=0.81.
      There was a strong association between health-related quality of life (HRQoL)
      (FAMS) and D-FIS (rS=0.70). CONCLUSIONS: In this study, D-FIS proved to be a
      feasible and valid instrument for measuring MSrelated fatigue, a frequent symptom
      associated with deterioration of patients' HRQoL.

PMID- 17548446
TI  - Enhancing physical activity adherence and well-being in multiple sclerosis: a
      randomised controlled trial.
AB  - Individuals with multiple sclerosis (MS) are more sedentary than the general
      population, increasing their propensity for reduced functional ability, mobility,
      and activities of daily living. Self-efficacy has been one of the most consistent
      determinants of physical activity across populations, including those with MS.
      However, no studies exist that have attempted to influence self-efficacy in MS
      patients, in an effort to improve physical activity participation. We conducted a
      three-month randomised, controlled trial (n=26), contrasting the effects of an
      efficacy-enhancement exercise condition and a control exercise condition on
      exercise adherence, well-being, and affective responses to exercise. Analyses
      indicated that individuals in the efficacy enhancement condition attended more
      exercise sessions, reported greater levels of well-being and exertion, and felt
      better following exercise than individuals in the standard care condition.
      Regardless of treatment condition, individuals with a stronger sense of exercise
      self-efficacy, who reported more enjoyment following the exercise sessions,
      demonstrated significantly greater adherence with the exercise program. We
      believe this to be the first empirical attempt to change physical activity
      behavior in persons with MS using a well-established theoretical framework to
      drive the intervention. Continued examination of self-efficacy as a determinant
      of behavior change in individuals with MS is needed.

PMID- 17548447
TI  - 'Fighting for everything': service experiences of people severely affected by
      multiple sclerosis.
AB  - BACKGROUND: No previous research exists specifically exploring the needs of those
      people severely affected by multiple sclerosis (MS). METHODS: Semi-structured
      interviews were conducted with people identified by the referring health or
      social care professional as being severely affected by their MS and informal
      carers, in order to explore their perceptions of their illness and care. The data
      were analysed for themes using the constant comparative approach. RESULTS: The
      data relate to 32 people severely affected by MS, who identified several broad
      themes, relating to loss and change, and provision of services and care. In
      relation to service provision, people with MS (PwMS) and their carers identified
      two, interlinked themes--a lack of continuity and co-ordination of care, and a
      lack of information about services, aids and adaptations, welfare benefits and
      end-of-life issues. A further theme was identified, which underpinned and linked
      the two other themes, that of ;fighting for everything'--a sense that people had
      to struggle for their needs to be met. CONCLUSION: There is a need to develop
      models of care in order to better meet patients and carers needs for information,
      co-ordination, and to reduce the feeling of struggling to receive services.

PMID- 17548448
TI  - Multiple sclerosis in Pakistan.
AB  - We describe retrospective data from the largest series of patients (n=142) with
      multiple sclerosis (MS) from Pakistan. Mean age at onset was 27 years, with a
      female to male ratio of 1.45:1. The disease onset was polysymptomatic in 75%
      patients. Motor weakness was the most common onset symptom (70%), followed by
      sensory symptoms (45%). Optico-spinal type of MS was seen in only 3% of patients
      The course was relapsing-remitting (RR) in 81%, primary progressive (PP) in 21%,
      and secondary progressive (SP) in 4% of patients. Almost three-fourths of the
      patients were moderately (45%) or severely (31%) disabled at the time of
      evaluation. Two-thirds of patients with severe disability had a mean disease
      duration of only 5.2 years. In conclusion, MS is not uncommon in Pakistan, and
      many patients were found to have severe disability despite short disease
      duration.

PMID- 17548449
TI  - Assessment of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D3 concentrations in
      male and female multiple sclerosis patients and control volunteers.
AB  - Populations with insufficient ultraviolet exposure and who consume diets low in
      vitamin D have low vitamin D status (plasma 25-hydroxyvitamin D (25(OH)D)
      concentrations) and a reported higher incidence of multiple sclerosis (MS). The
      active form of vitamin D, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), is an effective
      anti-inflammatory molecule. No research to date has assessed 1,25(OH)2D3
      concentrations in individuals with MS. In this study, plasma concentrations of
      25(OH)D, 1,25(OH)2D3 and parathyroid hormone (PTH) were measured in 29
      individuals with MS and 22 age- and sex-matched control volunteers. There were no
      significant differences in plasma PTH, 25(OH)D and 1,25(OH)2D3 concentrations
      between individuals with MS and control volunteers. Women with MS had
      significantly higher 25(OH)D and 1,25(OH)2D3 concentrations than men with MS
      (79.1+/-45.4 versus 50.2+/-15.3 nmol/L, P=0.019 and 103.8+/-36.8 versus 70.4+/
      28.7 pmol/L, P=0.019, respectively). There was a significant positive correlation
      between 25(OH)D and 1,25(OH)2D3 concentrations in all subjects (r=0.564,
      P=0.000), but secondary analysis revealed that the correlation was driven by
      women with MS (r=0.677, P=0.001). Significant sex differences in vitamin D
      metabolism were observed and were most marked in individuals with MS, suggesting
      that vitamin D requirements may differ between the sexes, as well as by
      underlying disease state.

PMID- 17548450
TI  - Conjugal multiple sclerosis in Isfahan, Iran: a population-based study.
AB  - Conjugal multiple sclerosis (MS) is a rare form of MS in which both spouses are
      affected, and at least one is affected after marriage. Among 1606 definite MS
      patients, 1076 were in marital relationship, among whom we identified six
      conjugal pairs, giving the conjugal rate of 0.5%. This rate is 12.5 times higher
      than the estimated risk of MS for the general population (0.04%). The observed
      conjugal rate suggests an increased risk of developing MS for MS patients'
      spouses, this could be due to transmission or, more likely, to the same
      environmental factors shared in adult life.

PMID- 17548451
TI  - Autologous hematopoietic stem cell transplantation for very active relapsing
      remitting multiple sclerosis: report of two cases.
AB  - Autologous hematopoietic stem cell transplantation (AHSCT) has been proposed as a
      rescue treatment in multiple sclerosis (MS) patients not responding to first- or
      second-line therapies. To date, most of the treated cases had a secondary
      progressive disease course. However, patients with high inflammatory activity,
      but no secondary progression of the disease, could be candidates to take greater
      advantage of AHSCT. In this paper, we report two cases with very active,
      relapsing-remitting (RR) MS, who underwent AHSCT, and obtained a dramatic
      resolution to disease activity.

PMID- 17548452
TI  - Neuromyelitis optica with clinical and histopathological involvement of the
      brain.
AB  - Diagnostic criteria for neuromyelitis optica (NMO) state that there should be no
      active disease outside the optic nerves and spinal cord. However, several cases
      have been described with symptomatic brain involvement. We describe an autopsy
      case of a patient with NMO and symptomatic involvement of the brain. The
      histopathology of the brain lesions is typical for NMO, with extensive macrophage
      infiltration, including perivascular accumulation of large numbers of
      eosinophils. This is the first case that clearly shows that in NMO, the
      histopathology of the brain lesions is identical to that of the lesions in the
      optic nerves and spinal cord.

PMID- 17548453
TI  - Autoimmune hemolytic anemia during interferon-beta-I b treatment for multiple
      sclerosis.
AB  - A 31-year-old patient with multiple sclerosis (MS), treated with interferon beta
      1b (IFNB-1b) for two years, presented with fatigue and dizziness. Coombs'
      positive autoimmune hemolytic anemia (AIHA) was found. Other potential etiologies
      of AIHA were ruled out. An association with IFNB-1b was highly suspected.
      Interferon therapy was discontinued and prednisone therapy instituted. There was
      resolution of the hemolytic anemia, and prednisone therapy was tapered gradually.
      To the best of our knowledge, there is no reported case of the development of
      AIHA associated with IFNB-1b use in MS patients. We conclude that if an
      unexplained drop in hematocrit occurs with a MS patient receiving IFNB-1b,
      autoimmune mediated hemolysis should also be considered.

PMID- 17548454
TI  - Gastroparesis in multiple sclerosis.

PMID- 17548455
TI  - The 'never-ending story' of the influence of blood specimen collection methods
      affecting the concentration, the zymographic profile and the usefulness of matrix
      metalloproteinases and their tissue inhibitors in multiple sclerosis
      diagnosis/prognosis: a landmark for limiting the misuse of serum samples.

PMID- 17548456
TI  - In vitro activity of ceftaroline (PPI-0903M, T-91825) against bacteria with
      defined resistance mechanisms and phenotypes.
AB  - BACKGROUND: Ceftaroline (PPI-0903M, T-91825) is a novel cephalosporin,
      administered as an N-phosphono prodrug. We investigated its in vitro activity and
      resistance selection potential. METHODS: MICs were determined by CLSI agar
      dilution, but with varied inocula. Mutant selection was investigated in single-
      and multi-step procedures. RESULTS: MICs for methicillin-resistant Staphylococcus
      aureus (MRSA) were 0.5-2 mg/L, compared with 0.12-0.25 mg/L for methicillin
      susceptible S. aureus; corresponding values for coagulase-negative staphylococci
      were 0.25-2 and 0.06-0.12 mg/L, respectively. Even with 2% NaCl added, all MRSA
      were susceptible at 2 mg/L. MICs for Enterococcus faecalis were from 0.25 to 8
      mg/L; E. faecium was resistant. MICs for Escherichia coli, Klebsiella spp.,
      Morganella morganii and Proteeae without acquired resistance were 0.06-0.5 mg/L
      versus 0.12-1 mg/L for Enterobacter, Serratia and Citrobacter spp. and 2-8 mg/L
      for Acinetobacter spp. MICs rose to 1-2 mg/L for many Enterobacteriaceae with
      classical TEM beta-lactamases, and were much higher for those with extended
      spectrum beta-lactamases (ESBLs), hyperproduced AmpC or K1 enzymes. MICs for
      strains with classical TEM/SHV beta-lactamases rose if the inoculum was increased
      to 10(6) cfu/spot; this effect was even more marked for those with ESBLs.
      Resistance due to Class A beta-lactamases was reversed by clavulanate. Geometric
      mean MICs were 0.005, 0.05 and 0.09 mg/L for penicillin-susceptible, 
      intermediate and -resistant Streptococcus pneumoniae strains, respectively-lower
      than for any comparator beta-lactam. Haemophilus influenzae and Moraxella
      catarrhalis were very susceptible, although with marginally raised MICs for beta
      lactamase-positive Moraxella strains and for haemophili with chromosomal
      ampicillin resistance. Ceftaroline selected AmpC-derepressed Enterobacter mutants
      similarly to cefotaxime in single-step experiments; in multi-step procedures it
      selected ESBL variants of blaTEM in E. coli. Resistance selection was not seen
      with S. aureus, H. influenzae or pneumococci. CONCLUSIONS: Ceftaroline has
      impressive anti-MRSA and anti-pneumococcal activity. Slight lability to classical
      TEM and SHV beta-lactamases is exceptional for an oxyimino-cephalosporin, but was
      reversible with clavulanate, as was the greater resistance mediated by ESBLs.
      Resistance selection occurred with Enterobacteriaceae, not MRSA.

PMID- 17548457
TI  - Extent of circulation of incorrectly labeled adenovirus 50 and 51 prototype
      preparations.

PMID- 17548458
TI  - Does one voriconazole breakpoint suit all Candida species?

PMID- 17548459
TI  - Tigecycline disk diffusion breakpoints of Acinetobacter spp.: a clinical point of
      view.

PMID- 17548460
TI  - Arthritis caused by Corynebacterium striatum: spontaneous infection?

PMID- 17548461
TI  - Possible misidentification of GSP[6] rotavirus as a novel strain detected in
      humans for the first time.

PMID- 17548462
TI  - Decrease in intracellular concentration causes the shift in Km value of efflux
      pump substrates.
AB  - Passive permeability and active efflux are parallel processes in transcellular
      flux. Therefore, the observed kinetics of a transporter substrate depends on both
      of these factors. The transporter expression has been shown to affect both the
      apparent K(m) and V(max) values. Kinetic parameters can be obtained from various
      experimental settings, but these do not necessarily reflect the situation in
      transcellular flux. Kinetic absorption models need reliable estimates of
      saturable kinetics when accurate in silico predictions are to be made. The effect
      of increasing P-glycoprotein expression on apparent transport kinetics was
      studied using quinidine and digoxin as model compounds. The intracellular
      concentrations of drugs during the transport process were also measured. A
      dynamic simulation model was constructed to study the observed data. The apparent
      K(m) and V(max) values increased as the P-glycoprotein expression increased.
      Simulations reproduced the shift in both kinetic parameters as a function of
      efflux pump expression. In addition, the apparent K(m) value showed a strong
      inverse relationship to the passive permeability. In contrast, the apparent
      V(max) value reached a maximum at intermediate passive permeability and declined
      above and below this passive permeability. The true V(max) and K(m) values were
      never reached. The shift in K(m) was assigned to a decrease in intracellular
      concentration at the P-glycoprotein interaction site with both experimental and
      simulation data. In conclusion, the apparent kinetic parameters in transcellular
      permeability assays depend on passive permeability and efflux pump activity.
      Therefore, parameters that are obtained from in vitro assays should be cautiously
      applied to in vivo predictions.

PMID- 17548463
TI  - Data-based mathematical modeling of vectorial transport across double-transfected
      polarized cells.
AB  - Vectorial transport of endogenous small molecules, toxins, and drugs across
      polarized epithelial cells contributes to their half-life in the organism and to
      detoxification. To study vectorial transport in a quantitative manner, an in
      vitro model was used that includes polarized MDCKII cells stably expressing the
      recombinant human uptake transporter OATP1B3 in their basolateral membrane and
      the recombinant ATP-driven efflux pump ABCC2 in their apical membrane. These
      double-transfected cells enabled mathematical modeling of the vectorial transport
      of the anionic prototype substance bromosulfophthalein (BSP) that has frequently
      been used to examine hepatobiliary transport. Time-dependent analyses of (3)H
      labeled BSP in the basolateral, intracellular, and apical compartments of cells
      cultured on filter membranes and efflux experiments in cells preloaded with BSP
      were performed. A mathematical model was fitted to the experimental data. Data
      based modeling was optimized by including endogenous transport processes in
      addition to the recombinant transport proteins. The predominant contributions to
      the overall vectorial transport of BSP were mediated by OATP1B3 (44%) and ABCC2
      (28%). Model comparison predicted a previously unrecognized endogenous
      basolateral efflux process as a negative contribution to total vectorial
      transport, amounting to 19%, which is in line with the detection of the
      basolateral efflux pump Abcc4 in MDCKII cells. Rate-determining steps in the
      vectorial transport were identified by calculating control coefficients. Data
      based mathematical modeling of vectorial transport of BSP as a model substance
      resulted in a quantitative description of this process and its components. The
      same systems biology approach may be applied to other cellular systems and to
      different substances.

PMID- 17548464
TI  - Characteristics of a 85Kr beta-particle source applied in Series 1 reference
      irradiations of DIS-1 direct ion storage dosemeters.
AB  - Characteristics necessary to specify an ISO 6980 Series 1 reference radiation
      field were determined for a commercially available 85Kr beta-particle source,
      using a BEAM EGS4 Monte Carlo code. The characteristics include residual maximum
      beta energy, E(res), and the uniformity of the dose rate over the calibration
      area. The E(res) and the uniformity were also determined experimentally, using an
      extrapolation ionization chamber (EC) and a 0.2 cm3 parallel plate ionization
      chamber, respectively. The depth-dose curve measured with the EC gave a value
      0.62 MeV for the E(res). Series 2 90Sr + 90Y and Series 1(85) Kr beta-particle
      sources calibrated for H(p)(0.07) at the secondary standard dosimetry laboratory
      (SSDL) of STUK were used to determine the energy and angular responses of DIS-1
      direct ion storage dosemeters. The averaged zero angle H(p)(0.07) responses to
      the 90Sr + 90Y and 85Kr reference radiations were 135 and 80%, respectively. The
      responses were normalized to 100%, H(p)(0.07) response to 137Cs photon radiation.

PMID- 17548465
TI  - Agm1/Pgm3-mediated sugar nucleotide synthesis is essential for hematopoiesis and
      development.
AB  - Carbohydrate modification of proteins includes N-linked and O-linked
      glycosylation, proteoglycan formation, glycosylphosphatidylinositol anchor
      synthesis, and O-GlcNAc modification. Each of these modifications requires the
      sugar nucleotide UDP-GlcNAc, which is produced via the hexosamine biosynthesis
      pathway. A key step in this pathway is the interconversion of GlcNAc-6-phosphate
      (GlcNAc-6-P) and GlcNAc-1-P, catalyzed by phosphoglucomutase 3 (Pgm3). In this
      paper, we describe two hypomorphic alleles of mouse Pgm3 and show there are
      specific physiological consequences of a graded reduction in Pgm3 activity and
      global UDP-GlcNAc levels. Whereas mice lacking Pgm3 die prior to implantation,
      animals with less severe reductions in enzyme activity are sterile, exhibit
      changes in pancreatic architecture, and are anemic, leukopenic, and
      thrombocytopenic. These phenotypes are accompanied by specific rather than
      wholesale changes in protein glycosylation, suggesting that while universally
      required, the functions of certain proteins and, as a consequence, certain cell
      types are especially sensitive to reductions in Pgm3 activity.

PMID- 17548466
TI  - Key role for intracellular K+ and protein kinases Sat4/Hal4 and Hal5 in the
      plasma membrane stabilization of yeast nutrient transporters.
AB  - K+ transport in living cells must be tightly controlled because it affects basic
      physiological parameters such as turgor, membrane potential, ionic strength, and
      pH. In yeast, the major high-affinity K+ transporter, Trk1, is inhibited by high
      intracellular K+ levels and positively regulated by two redundant "halotolerance"
      protein kinases, Sat4/Hal4 and Hal5. Here we show that these kinases are not
      required for Trk1 activity; rather, they stabilize the transporter at the plasma
      membrane under low K+ conditions, preventing its endocytosis and vacuolar
      degradation. High concentrations (0.2 M) of K+, but not Na+ or sorbitol,
      transported by undefined low-affinity systems, maintain Trk1 at the plasma
      membrane in the hal4 hal5 mutant. Other nutrient transporters, such as Can1
      (arginine permease), Fur4 (uracil permease), and Hxt1 (low-affinity glucose
      permease), are also destabilized in the hal4 hal5 mutant under low K+ conditions
      and, in the case of Can1, are stabilized by high K+ concentrations. Other plasma
      membrane proteins such as Pma1 (H+ -pumping ATPase) and Sur7 (an eisosomal
      protein) are not regulated by halotolerance kinases or by high K+ levels. This
      novel regulatory mechanism of nutrient transporters may participate in the
      quiescence/growth transition and could result from effects of intracellular K+
      and halotolerance kinases on membrane trafficking and/or on the transporters
      themselves.

PMID- 17548468
TI  - SUMO modification regulates MafB-driven macrophage differentiation by enabling
      Myb-dependent transcriptional repression.
AB  - During the execution of differentiation programs, lineage-specific transcription
      factors are in competition with antagonistic factors that drive progenitor
      proliferation. Thus, the myeloid transcription factor MafB promotes macrophage
      differentiation of myeloid progenitors, but a constitutively active Myb
      transcription factor (v-Myb) can maintain proliferation and block
      differentiation. Little is known, however, about the regulatory mechanisms that
      control such competing activities. Here we report that the small ubiquitin-like
      protein SUMO-1 can modify MafB in vitro and in vivo on lysines 32 and 297. The
      absence of MafB SUMO modification increased MafB-driven transactivation and
      macrophage differentiation potential but inhibited cell cycle progression and
      myeloid progenitor growth. Furthermore, we observed that direct repression of
      MafB transactivation by v-Myb was strictly dependent on MafB SUMO modification.
      Consequently, a SUMOylation-deficient MafB K32R K297R (K32,297R) mutant could
      specify macrophage fate even after activation of inducible Myb alleles and resist
      their differentiation-inhibiting activity. Our findings suggest that SUMO
      modification of MafB affects the balance between myeloid progenitor expansion and
      terminal macrophage differentiation by controlling MafB transactivation capacity
      and susceptibility to Myb repression. SUMO modification of lineage-specific
      transcription factors may thus modulate transcription factor antagonism to
      control tissue homeostasis in the hematopoietic system.

PMID- 17548467
TI  - Nerve growth factor stimulates the concentration of TrkA within lipid rafts and
      extracellular signal-regulated kinase activation through c-Cbl-associated
      protein.
AB  - Nerve growth factor (NGF) acts through its receptor, TrkA, to elicit the neuronal
      differentiation of PC12 cells through the action of extracellular signal
      regulated kinase 1 (ERK1) and ERK2. Upon NGF binding, TrkA translocates and
      concentrates in cholesterol-rich membrane microdomains or lipid rafts,
      facilitating formation of receptor-associated signaling complexes, activation of
      downstream signaling pathways, and internalization into endosomes. We have
      investigated the mechanisms responsible for the localization of TrkA within lipid
      rafts and its ability to activate ERK1 and ERK2. We report that NGF treatment
      results in the translocation of activated forms of TrkA to lipid rafts, and this
      localization is important for efficient activation of the ERKs. TrkA is recruited
      and retained within lipid rafts through its association with flotillin, an
      intrinsic constituent of these membrane microdomains, via the adapter protein, c
      Cbl associated protein (CAP). Mutant forms of CAP that lack protein interaction
      domains block TrkA localization to lipid rafts and attenuate ERK activation.
      Importantly, suppression of endogenous CAP expression inhibited NGF-stimulated
      neurite outgrowth from primary dorsal root ganglion neurons. These data provide a
      mechanism for the lipid raft localization of TrkA and establish the importance of
      the CAP adaptor protein for NGF activation of the ERKs and neuronal
      differentiation.

PMID- 17548469
TI  - Stage-specific secretion of HMGB1 in cartilage regulates endochondral
      ossification.
AB  - High mobility group box 1 protein (HMGB1) is a chromatin protein that has a dual
      function as a nuclear factor and as an extracellular factor. Extracellular HMGB1
      released by damaged cells acts as a chemoattractant, as well as a proinflammatory
      cytokine, suggesting that HMGB1 is tightly connected to the process of tissue
      organization. However, the role of HMGB1 in bone and cartilage that undergo
      remodeling during embryogenesis, tissue repair, and disease is largely unknown.
      We show here that the stage-specific secretion of HMGB1 in cartilage regulates
      endochondral ossification. We analyzed the skeletal development of Hmgb1(-/-)
      mice during embryogenesis and found that endochondral ossification is
      significantly impaired due to the delay of cartilage invasion by osteoclasts,
      osteoblasts, and blood vessels. Immunohistochemical analysis revealed that HMGB1
      protein accumulated in the cytosol of hypertrophic chondrocytes at growth plates,
      and its extracellular release from the chondrocytes was verified by organ
      culture. Furthermore, we demonstrated that the chondrocyte-secreted HMGB1
      functions as a chemoattractant for osteoclasts and osteoblasts, as well as for
      endothelial cells, further supporting the conclusion that Hmgb1(-/-) mice are
      defective in cell invasion. Collectively, these findings suggest that HMGB1
      released from differentiating chondrocytes acts, at least in part, as a regulator
      of endochondral ossification during osteogenesis.

PMID- 17548470
TI  - Linear distance from the locus control region determines epsilon-globin
      transcriptional activity.
AB  - Enhancer elements modulate promoter activity over vast chromosomal distances, and
      mechanisms that ensure restrictive interactions between promoters and enhancers
      are critical for proper control of gene expression. The human beta-globin locus
      control region (LCR) activates expression of five genes in erythroid cells,
      including the proximal embryonic epsilon- and the distal adult beta-globin genes.
      To test for possible distance sensitivity of the genes to the LCR, we extended
      the distance between the LCR and genes by 2.3 kbp within the context of a yeast
      artificial chromosome, followed by the generation of transgenic mice (TgM). In
      these TgM lines, epsilon-globin gene expression decreased by 90%, while the more
      distantly located gamma- or beta-globin genes were not affected. Remarkably,
      introduction of a consensus EKLF binding site into the epsilon-globin promoter
      rendered its expression distance insensitive; when tested in an EKLF-null genetic
      background, expression of the mutant epsilon-globin gene was severely
      compromised. Thus, the epsilon-globin gene differs in its distance sensitivity to
      the LCR from the other beta-like globin genes, which is, at least in part,
      determined by the transcription factor EKLF.

PMID- 17548471
TI  - Regulation of urokinase receptor expression by p53: novel role in stabilization
      of uPAR mRNA.
AB  - We found that p53-deficient (p53(-/-)) lung carcinoma (H1299) cells express
      robust levels of cell surface uPAR and uPAR mRNA. Expression of p53 protein in
      p53(-/-) cells suppressed basal and urokinase (uPA)-induced cell surface uPAR
      protein and increased uPAR mRNA degradation. Inhibition of p53 by RNA silencing
      in Beas2B human airway epithelial cells conversely increased basal as well as uPA
      mediated uPAR expression and stabilized uPAR mRNA. Purified p53 protein
      specifically binds to the uPAR mRNA 3' untranslated region (3'UTR), and
      endogenous uPAR mRNA associates with p53. The p53 binding region involves a 37
      nucleotide uPAR 3'UTR sequence, and insertion of the p53 binding sequence into
      beta-globin mRNA destabilized beta-globin mRNA. Inhibition of p53 expression in
      these cells reverses decay of chimeric beta-globin-uPAR mRNA. These observations
      demonstrate a novel regulatory role for p53 as a uPAR mRNA binding protein that
      down-regulates uPAR expression, destabilizes uPAR mRNA, and thereby contributes
      to the viability of human airway epithelial or lung carcinoma cells.

PMID- 17548472
TI  - The RNA-binding protein HuR promotes cell migration and cell invasion by
      stabilizing the beta-actin mRNA in a U-rich-element-dependent manner.
AB  - A high expression level of the beta-actin protein is required for important
      biological mechanisms, such as maintaining cell shape, growth, and motility.
      Although the elevated cellular level of the beta-actin protein is directly linked
      to the long half-life of its mRNA, the molecular mechanisms responsible for this
      effect are unknown. Here we show that the RNA-binding protein HuR stabilizes the
      beta-actin mRNA by associating with a uridine-rich element within its 3'
      untranslated region. Using RNA interference to knock down the expression of HuR
      in HeLa cells, we demonstrate that HuR plays an important role in the
      stabilization but not in the nuclear/cytoplasmic distribution of the beta-actin
      mRNA. HuR depletion in HeLa cells alters key beta-actin-based cytoskeleton
      functions, such as cell adhesion, migration, and invasion, and these defects
      correlate with a loss of the actin stress fiber network. Together our data
      establish that the posttranscriptional event involving HuR-mediated beta-actin
      mRNA stabilization could be a part of the regulatory mechanisms responsible for
      maintaining cell integrity, which is a prerequisite for avoiding transformation
      and tumor formation.

PMID- 17548473
TI  - Prion protein repeat expansion results in increased aggregation and reveals
      phenotypic variability.
AB  - Mammalian prion diseases are fatal neurodegenerative disorders dependent on the
      prion protein PrP. Expansion of the oligopeptide repeats (ORE) found in PrP is
      associated with inherited prion diseases. Patients with ORE frequently harbor PrP
      aggregates, but other factors may contribute to pathology, as they often present
      with unexplained phenotypic variability. We created chimeric yeast-mammalian
      prion proteins to examine the influence of the PrP ORE on prion properties in
      yeast. Remarkably, all chimeric proteins maintained prion characteristics. The
      largest repeat expansion chimera displayed a higher propensity to maintain a self
      propagating aggregated state. Strikingly, the repeat expansion conferred
      increased conformational flexibility, as observed by enhanced phenotypic
      variation. Furthermore, the repeat expansion chimera displayed an increased rate
      of prion conversion, but only in the presence of another aggregate, the [RNQ+]
      prion. We suggest that the PrP ORE increases the conformational flexibility of
      the prion protein, thereby enhancing the formation of multiple distinct aggregate
      structures and allowing more frequent prion conversion. Both of these
      characteristics may contribute to the phenotypic variability associated with PrP
      repeat expansion diseases.

PMID- 17548474
TI  - The kinase inhibitor sorafenib induces cell death through a process involving
      induction of endoplasmic reticulum stress.
AB  - Sorafenib is a multikinase inhibitor that induces apoptosis in human leukemia and
      other malignant cells. Recently, we demonstrated that sorafenib diminishes Mcl-1
      protein expression by inhibiting translation through a MEK1/2-ERK1/2 signaling
      independent mechanism and that this phenomenon plays a key functional role in
      sorafenib-mediated lethality. Here, we report that inducible expression of
      constitutively active MEK1 fails to protect cells from sorafenib-mediated
      lethality, indicating that sorafenib-induced cell death is unrelated to MEK1/2
      ERK1/2 pathway inactivation. Notably, treatment with sorafenib induced
      endoplasmic reticulum (ER) stress in human leukemia cells (U937) manifested by
      immediate cytosolic-calcium mobilization, GADD153 and GADD34 protein induction,
      PKR-like ER kinase (PERK) and eukaryotic initiation factor 2alpha (eIF2alpha)
      phosphorylation, XBP1 splicing, and a general reduction in protein synthesis as
      assessed by [35S]methionine incorporation. These events were accompanied by
      pronounced generation of reactive oxygen species through a mechanism dependent
      upon cytosolic-calcium mobilization and a significant decline in GRP78/Bip
      protein levels. Interestingly, enforced expression of IRE1alpha markedly reduced
      sorafenib-mediated apoptosis, whereas knockdown of IRE1alpha or XBP1, disruption
      of PERK activity, or inhibition of eIF2alpha phosphorylation enhanced sorafenib
      mediated lethality. Finally, downregulation of caspase-2 or caspase-4 by small
      interfering RNA significantly diminished apoptosis induced by sorafenib.
      Together, these findings demonstrate that ER stress represents a central
      component of a MEK1/2-ERK1/2-independent cell death program triggered by
      sorafenib.

PMID- 17548475
TI  - Poly(ADP-ribose) polymerase 1 accelerates single-strand break repair in concert
      with poly(ADP-ribose) glycohydrolase.
AB  - Single-strand breaks are the commonest lesions arising in cells, and defects in
      their repair are implicated in neurodegenerative disease. One of the earliest
      events during single-strand break repair (SSBR) is the rapid synthesis of
      poly(ADP-ribose) (PAR) by poly(ADP-ribose) polymerase (PARP), followed by its
      rapid degradation by poly(ADP-ribose) glycohydrolase (PARG). While the synthesis
      of poly(ADP-ribose) is important for rapid rates of chromosomal SSBR, the
      relative importance of poly(ADP-ribose) polymerase 1 (PARP-1) and PARP-2 and of
      the subsequent degradation of PAR by PARG is unclear. Here we have quantified
      SSBR rates in human A549 cells depleted of PARP-1, PARP-2, and PARG, both
      separately and in combination. We report that whereas PARP-1 is critical for
      rapid global rates of SSBR in human A549 cells, depletion of PARP-2 has only a
      minor impact, even in the presence of depleted levels of PARP-1. Moreover, we
      identify PARG as a novel and critical component of SSBR that accelerates this
      process in concert with PARP-1.

PMID- 17548476
TI  - Activation of the c-Jun N-terminal kinase pathway by MST1 is essential and
      sufficient for the induction of chromatin condensation during apoptosis.
AB  - Chromatin condensation is the most recognizable nuclear hallmark of apoptosis.
      Cleavage and activation of MST1 by caspases induce chromatin condensation. It was
      previously reported that, during apoptosis, activated MST1 induced c-Jun N
      terminal kinase (JNK) activation and also phosphorylated histone H2B. However,
      which of these mechanisms underlies MST1's induction of chromatin condensation
      has yet to be clarified. Here, we report that MST1-mediated activation of JNK is
      both essential and sufficient for chromatin condensation. MST1 activation did not
      result in chromatin condensation in mitogen-activate protein kinase kinase 4
      (MKK4)/MKK7 double knockout (MKK4/7 DKO) embryonic stem (ES) cells, which
      genetically lack the ability to activate JNK. On the other hand, constitutively
      active JNK was able to induce chromatin condensation in MKK4/7 DKO ES cells. In
      contrast, histone H2B phosphorylation did not correlate with chromatin
      condensation in wild-type ES cells. Finally, inhibition of JNK as well as
      inhibitor of caspase-activated DNase blocked chromatin condensation during Fas
      mediated apoptosis of Jurkat cells. Taken together, our results indicate that
      caspase-mediated cleavage of MST1, followed by MST1-mediated activation of the
      JNK pathway, is the mechanism responsible for inducing chromatin condensation
      during apoptosis.

PMID- 17548477
TI  - Ribosomal protein L33 is required for ribosome biogenesis, subunit joining, and
      repression of GCN4 translation.
AB  - We identified a mutation in the 60S ribosomal protein L33A (rpl33a-G76R) that
      elicits derepression of GCN4 translation (Gcd- phenotype) by allowing scanning
      preinitiation complexes to bypass inhibitory upstream open reading frame 4
      (uORF4) independently of prior uORF1 translation and reinitiation. At 37 degrees
      C, rpl33a-G76R confers defects in 60S biogenesis comparable to those produced by
      the deletion of RPL33A (DeltaA). At 28 degrees C, however, the 60S biogenesis
      defect is less severe in rpl33a-G76R than in DeltaA cells, yet rpl33a-G76R
      confers greater derepression of GCN4 and a larger reduction in general
      translation. Hence, it appears that rpl33a-G76R has a stronger effect on
      ribosomal-subunit joining than does a comparable reduction of wild-type 60S
      levels conferred by DeltaA. We suggest that rpl33a-G76R alters the 60S subunit in
      a way that impedes ribosomal-subunit joining and thereby allows 48S rRNA
      complexes to abort initiation at uORF4, resume scanning, and initiate downstream
      at GCN4. Because overexpressing tRNAiMet suppresses the Gcd- phenotype of rpl33a
      G76R cells, dissociation of tRNAiMet from the 40S subunit may be responsible for
      abortive initiation at uORF4 in this mutant. We further demonstrate that rpl33a
      G76R impairs the efficient processing of 35S and 27S pre-rRNAs and reduces the
      accumulation of all four mature rRNAs, indicating an important role for L33 in
      the biogenesis of both ribosomal subunits.

PMID- 17548478
TI  - Inactivation of traP has no effect on the agr quorum-sensing system or virulence
      of Staphylococcus aureus.
AB  - The success of Staphylococcus aureus as a pathogen can largely be attributed to
      the plethora of genetic regulators encoded within its genome that temporally
      regulate its arsenal of virulence determinants throughout its virulence
      lifestyle. Arguably the most important of these is the two-component, quorum
      sensing system agr. Over the last decade, the controversial presence of a second
      quorum-sensing system (the TRAP system) has been proposed, and it has been mooted
      to function as the master regulator of virulence in S. aureus by modulating agr.
      Mutants defective in TRAP are reported to be devoid of agr expression, lacking in
      hemolytic activity, essentially deficient in the secretion of virulence
      determinants, and avirulent in infection models. A number of research groups have
      questioned the validity of the TRAP findings in recent years; however, a thorough
      and independent analysis of its role in S. aureus physiology and pathogenesis has
      not been forthcoming. Therefore, we have undertaken such an analysis of the TRAP
      locus of S. aureus. We found that a traP mutant was equally hemolytic as the wild
      type strain. Furthermore, transcriptional profiling found no alterations in the
      traP mutant in expression levels of agr or in expression levels of multiple agr
      regulated genes (hla, sspA, and spa). Analysis of secreted and surface proteins
      of the traP mutant revealed no deviation in comparison to the parent. Finally,
      analysis conducted using a murine model of S. aureus septic arthritis revealed
      that, in contrast to an agr mutant, the traP mutant was just as virulent as the
      wild-type strain.

PMID- 17548479
TI  - Mutation of traP in Staphylococcus aureus has no impact on expression of agr or
      biofilm formation.
AB  - To investigate the regulatory role of traP (target of RNAIII-activating peptide)
      in Staphylococcus aureus, we generated traP mutations in the clinical isolates
      UAMS-1 and USA300. In neither case did mutation of traP affect expression of the
      accessory gene regulator (agr) or the ability to form a biofilm. We were also
      unable to confirm that mutation of traP in the prototype 8325-4 laboratory strain
      RN6390 results in reduced expression of agr, reduced hemolytic activity, or an
      altered capacity to form a biofilm.

PMID- 17548480
TI  - Scavenger receptor A dampens induction of inflammation in response to the fungal
      pathogen Pneumocystis carinii.
AB  - Alveolar macrophages are the effector cells largely responsible for clearance of
      Pneumocystis carinii from the lungs. Binding of organisms to beta-glucan and
      mannose receptors has been shown to stimulate phagocytosis of the organisms. To
      further define the mechanisms used by alveolar macrophages for clearance of P.
      carinii, mice deficient in the expression of scavenger receptor A (SRA) were
      infected with P. carinii, and clearance of organisms was monitored over time. SRA
      deficient (SRAKO) mice consistently cleared P. carinii faster than did wild-type
      control mice. Expedited clearance corresponded to elevated numbers of activated
      CD4(+) T cells in the alveolar spaces of SRAKO mice compared to wild-type mice.
      Alveolar macrophages from SRAKO mice had increased expression of CD11b on their
      surfaces, consistent with an activated phenotype. However, they were not more
      phagocytic than macrophages expressing SRA, as measured by an in vivo
      phagocytosis assay. SRAKO alveolar macrophages produced significantly more tumor
      necrosis factor alpha (TNF-alpha) than wild-type macrophages when stimulated with
      lipopolysaccharide in vitro but less TNF-alpha in response to P. carinii in
      vitro. However, upon in vivo stimulation, SRAKO mice produced significantly more
      TNF-alpha, interleukin 12 (IL-12), and IL-18 in response to P. carinii infection
      than did wild-type mice. Together, these data indicate that SRA controls
      inflammatory cytokines produced by alveolar macrophages in the context of P.
      carinii infection.

PMID- 17548481
TI  - The secreted pyomelanin pigment of Legionella pneumophila confers ferric
      reductase activity.
AB  - The virulence of Legionella pneumophila is dependent upon its capacity to acquire
      iron. To identify genes involved in expression of its siderophore, we screened a
      mutagenized population of L. pneumophila for strains that were no longer able to
      rescue the growth of a ferrous transport mutant. However, an unusual mutant was
      obtained that displayed a strong inhibitory effect on the feoB mutant. Due to an
      insertion in hmgA that encodes homogentisate 1,2-dioxygenase, the mutant secreted
      increased levels of pyomelanin, the L. pneumophila pigment that is derived from
      secreted homogentisic acid (HGA). Thus, we hypothesized that L. pneumophila
      secreted HGA-melanin has intrinsic ferric reductase activity, converting Fe(3+)
      to Fe(2+), but that hyperpigmentation results in excessive reduction of iron that
      can, in the case of the feoB mutant, be inhibitory to growth. In support of this
      hypothesis, we demonstrated, for the first time, that wild-type L. pneumophila
      secretes ferric reductase activity. Moreover, whereas the hyperpigmented mutant
      had increased secreted activity, an lly mutant specifically impaired for pigment
      production lacked the activity. Compatible with the nature of HGA-melanins, the
      secreted ferric reductase activity was positively influenced by the amount of
      tyrosine in the growth medium, resistant to protease, acid precipitable, and
      heterogeneous in size. Together, these data represent the first demonstration of
      pyomelanin-mediated ferric reduction by a pathogenic bacterium.

PMID- 17548482
TI  - Net replication of Salmonella enterica serovars Typhimurium and Choleraesuis in
      porcine intestinal mucosa and nodes is associated with their differential
      virulence.
AB  - Salmonella enterica is a facultative intracellular pathogen of worldwide
      importance and causes a spectrum of diseases depending on serovar- and host
      specific factors. Oral infection of pigs with S. enterica serovar Typhimurium
      strain 4/74 produces acute enteritis but is rarely fatal, whereas serovar
      Choleraesuis strain A50 causes systemic disease with a high mortality rate. With
      a porcine ligated ileal loop model, we observed that systemic virulence of
      serovar Choleraesuis A50 is not associated with enhanced intestinal invasion,
      secretory responses, or neutrophil recruitment compared to serovar Typhimurium
      4/74. The net growth in vivo of serovar Choleraesuis A50 and serovar Typhimurium
      4/74 was monitored following oral inoculation of pigs with strains harboring
      pHSG422, which exhibits temperature-sensitive replication. Analysis of plasmid
      partitioning revealed that the enteric virulence of serovar Typhimurium 4/74
      relative to that of serovar Choleraesuis A50 is associated with rapid replication
      in the intestinal wall, whereas systemic virulence of serovar Choleraesuis A50 is
      associated with enhanced persistence in intestinal mesenteric lymph nodes. Faster
      replication of serovar Typhimurium, compared to that of serovar Choleraesuis, in
      the intestinal mucosa was associated with greater induction of the
      proinflammatory cytokines tumor necrosis factor alpha, interleukin-8 (IL-8), and
      IL-18 as detected by reverse transcriptase PCR analysis of transcripts from
      infected mucosa. During replication in batch culture and porcine alveolar
      macrophages, transcription of genes encoding components of type III secretion
      systems 1 (sipC) and 2 (sseC) was observed to be significantly higher in serovar
      Typhimurium 4/74 than in serovar Choleraesuis A50, and this may contribute to the
      differences in epithelial invasion and intracellular proliferation. The rapid
      induction of proinflammatory responses by strain 4/74 may explain why pigs
      confine serovar Typhimurium infection to the intestines, whereas slow replication
      of serovar Choleraesuis may enable it to evade host innate immunity and thus
      disseminate by stealth.

PMID- 17548483
TI  - Disease burden due to enterotoxigenic Escherichia coli in the first 2 years of
      life in an urban community in Bangladesh.
AB  - A cohort of 321 children was followed from birth up to 2 years of age to
      determine the incidence of enterotoxigenic Escherichia coli (ETEC) in Bangladesh.
      The average number of diarrheal days and incidence rates were 6.6 and
      2.3/child/year, respectively. ETEC was the most common pathogen and was isolated
      in 19.5% cases, with an incidence of 0.5 episode/child/year. The prevalence of
      rotavirus diarrhea was lower (10%). ETEC expressing the heat-stable enterotoxin
      (ST) was predominant. Strains isolated from diarrheal cases were positive for
      colonization factors (CFs) in higher frequency (66%) than from healthy children
      (33%) (P < 0.001). The heat-labile toxin (LT)-positive strains from healthy
      children were more often CF negative (92%) than those isolated from children with
      diarrhea (73%) (P < 0.001). In children with symptomatic or asymptomatic
      infections by CFA/I, CS1 plus CS3, CS2 plus CS3, or CS5 plus CS6 strains, a
      repeat episode of diarrhea or infection by the homologous CF type was uncommon.
      Repeat symptomatic infections were noted mostly for LT- and ST-expressing ETEC.
      ETEC diarrhea was more prevalent in children in the A and AB groups than in those
      in the O blood group (P = 0.032 to 0.023). Children with ETEC diarrhea were
      underweight and growth stunted at the 2-year follow-up period, showing the
      importance of strategies to prevent and decrease ETEC diarrheal morbidity in
      children.

PMID- 17548484
TI  - Growth and growth hormone therapy in subjects with mulibrey nanism.
AB  - OBJECTIVES: Mulibrey nanism is a monogenic disorder with prenatal-onset growth
      restriction, mild dysmorphic features, and a strong tendency for insulin
      resistance but no major neurologic handicap. Growth hormone therapy has been
      shown to promote short-term growth in children born small for gestational age,
      but the experience with long-term therapy is insufficient. Growth in patients
      with mulibrey nanism has not been analyzed previously in detail. METHODS: We
      evaluated the natural growth pattern and long-term impact of growth hormone
      treatment in the largest cohort of subjects with mulibrey nanism to date. The
      study included 72 living subjects followed up to 30 years. Thirty (18 female)
      were treated with recombinant human growth hormone for a median period of 5.7
      years. Patients were reviewed at baseline and every 6 to 12 months during the
      therapy. Evaluation included assessment of height, weight, and pubertal status
      and laboratory analyses. Glucose metabolism was evaluated by oral glucose
      tolerance test. RESULTS: The patients were born small for gestational age with
      immature craniofacial features. They experienced a continuous deceleration in
      height (median decrement of 1.1 SDS) and weight for height (median reduction of
      17%) in infancy followed by an incomplete catch-up growth lasting up to school
      age. The final adult height averaged 136 cm in girls and 150 cm in boys. Growth
      hormone treatment improved the prepubertal growth but had only little impact on
      adult height (+5 cm). The treated subjects showed earlier bone maturation and
      growth arrest but not a significant increase in insulin resistance. On the
      contrary, the subjects who were treated with growth hormone were slimmer and had
      less metabolic syndrome as young adults. CONCLUSIONS: The patients with mulibrey
      nanism showed a distinct postnatal growth pattern. The growth hormone treatment
      was safe and induced a good short-term effect, but the impact on the adult height
      remained modest.

PMID- 17548485
TI  - Detection and significance of serum protein marker of Hirschsprung disease.
AB  - OBJECTIVE: The objective of this study was to identify a specific fingerprint
      chromatogram model of serum proteins for early screening and diagnosis of
      Hirschsprung disease. METHODS: To detect the protein mass spectrograms of 78
      serum specimens (42 specimens of Hirschsprung disease, 16 specimens of adhesive
      ileus including appendicitis and Meckel diverticulum after operation and
      inflammatory bowel disease, and 20 specimens of normal control subjects), we used
      surface-enhanced laser desorption/ionization time of flight mass spectrometry
      technology, combined with bioinformatics methods (support vector machine) to
      develop and compare protein mass spectrograms from serum samples. RESULTS: We
      identified 3 protein markers, the mass-to-charge ratio of which is positioned at
      3221.7, 5639.2, and 6884.2 from the fingerprint chromatogram model of serum
      protein for early screening and diagnosis of Hirschsprung disease. The markers
      had 100% sensitivity and specificity. CONCLUSION: The fingerprint chromatogram
      model of serum protein using surface-enhanced laser desorption/ionization time of
      flight mass spectrometry technology combining support vector machine is a new
      method of early screening and diagnosis of Hirschsprung disease that is worthy of
      additional research and application.

PMID- 17548486
TI  - Hematologic and blood biochemistry monitoring during methylphenidate treatment in
      children with attention-deficit/hyperactivity disorder: 2-year, open-label study
      results.
AB  - OBJECTIVES: Patients receiving methylphenidate for the management of attention
      deficit/hyperactivity disorder are recommended to receive periodic hematologic
      monitoring. The objective of this study was to evaluate the long-term effects of
      methylphenidate treatment on blood biochemistry and hematologic values. METHODS:
      This study involved a detailed analysis of changes in hematologic and blood
      biochemistry values over the course of a 2-year study of once-daily OROS
      methylphenidate in otherwise healthy children aged 6 to 13 years with attention
      deficit/hyperactivity disorder. Routine hematologic and blood biochemistry
      assessments were performed at baseline, at 6 and 12 months during study
      treatment, and at the end of the study. RESULTS: Of the 407 subjects enrolled in
      the study, 289 completed year 1, and 229 completed 21 of 24 months. No subject
      was excluded from entry into the study or discontinued from the study because of
      abnormalities of any of the blood chemistries evaluated. There were no clinically
      significant changes from baseline in mean values for hematologic or blood
      biochemistry parameters. For most values, the mean change in value over the
      course of the study was <5%. CONCLUSIONS: These longer-term data suggest that
      chronic therapy with OROS methylphenidate has no clinically significant impact on
      laboratory values, challenging the necessity of routine hematologic monitoring in
      otherwise healthy children with attention-deficit/hyperactivity disorder who are
      treated with methylphenidate.

PMID- 17548487
TI  - Fluoroquinolone resistance in atypical pneumococci and oral streptococci:
      evidence of horizontal gene transfer of fluoroquinolone resistance determinants
      from Streptococcus pneumoniae.
AB  - Atypical strains, presumed to be pneumococcus, with ciprofloxacin MICs of > or
      =4.0 microg/ml and unique sequence variations within the quinolone resistance
      determining regions (QRDRs) of the gyrase and topoisomerase genes in comparison
      with the Streptococcus pneumoniae R6 strain, were examined. These strains were
      reidentified using phenotypic methods, including detection of optochin
      susceptibility, bile solubility, and agglutination by serotype-specific antisera,
      and genotypic methods, including detection of pneumolysin and autolysin genes by
      PCR, 16S rRNA sequencing, and multilocus sequence typing (MLST). The analysis
      based on concatenated sequences of the six MLST loci distinguished the "atypical"
      strains from pneumococci, and these strains clustered closely with S. mitis.
      However, all these strains and five of nine strains from the viridans
      streptococcal group possessed one to three gyrA, gyrB, parC, and parE genes whose
      QRDR sequences clustered with those of S. pneumoniae, providing evidence of
      horizontal transfer of the QRDRs of the gyrase and topoisomerase genes from
      pneumococci into viridans streptococci. These genes also conferred
      fluoroquinolone resistance to viridans streptococci. In addition, the
      fluoroquinolone resistance determinants of 32 well-characterized Streptococcus
      mitis and Streptococcus oralis strains from bacteremic patients were also
      compared. These strains have unique amino acid substitutions in GyrA and ParC
      that were distinguishable from those in fluoroquinolone-resistant pneumococci and
      the "atypical" isolates. Both recombinational events and de novo mutations play
      an important role in the development of fluoroquinolone resistance.

PMID- 17548488
TI  - Bound to shock: protection from lethal endotoxemic shock by a novel, nontoxic,
      alkylpolyamine lipopolysaccharide sequestrant.
AB  - Lipopolysaccharide (LPS), or endotoxin, a structural component of gram-negative
      bacterial outer membranes, plays a key role in the pathogenesis of septic shock,
      a syndrome of severe systemic inflammation which leads to multiple-system organ
      failure. Despite advances in antimicrobial chemotherapy, sepsis continues to be
      the commonest cause of death in the critically ill patient. This is attributable
      to the lack of therapeutic options that aim at limiting the exposure to the toxin
      and the prevention of subsequent downstream inflammatory processes. Polymyxin B
      (PMB), a peptide antibiotic, is a prototype small molecule that binds and
      neutralizes LPS toxicity. However, the antibiotic is too toxic for systemic use
      as an LPS sequestrant. Based on a nuclear magnetic resonance-derived model of
      polymyxin B-LPS complex, we had earlier identified the pharmacophore necessary
      for optimal recognition and neutralization of the toxin. Iterative cycles of
      pharmacophore-based ligand design and evaluation have yielded a synthetically
      easily accessible N(1),mono-alkyl-mono-homologated spermine derivative, DS-96. We
      have found that DS-96 binds LPS and neutralizes its toxicity with a potency
      indistinguishable from that of PMB in a wide range of in vitro assays, affords
      complete protection in a murine model of LPS-induced lethality, and is apparently
      nontoxic in vertebrate animal models.

PMID- 17548489
TI  - Influence of morbid obesity on the single-dose pharmacokinetics of daptomycin.
AB  - The present study characterized the single-dose pharmacokinetics of daptomycin
      dosed as 4 mg/kg of total body weight (TBW) in seven morbidly obese and seven age
      , sex-, race-, and serum creatinine-matched healthy subjects. The glomerular
      filtration rate (GFR) was measured for both groups following a single bolus
      injection of [(125)I]sodium iothalamate. Noncompartmental analysis was used to
      determine the pharmacokinetic parameters, and these values were normalized
      against TBW, ideal body weight (IBW), and fat-free weight (FFW) for comparison of
      the two groups. All subjects enrolled in this study were female, and the mean (+/
      standard deviation) body mass index was 46.2 +/- 5.5 kg/m(2) or 21.8 +/- 1.9
      kg/m(2) for the morbidly obese or normal-weight group, respectively. The maximum
      plasma concentration and area under the concentration-time curve from dosing to
      24 h were approximately 60% higher (P < 0.05) in the morbidly obese group than in
      the normal-weight group, and these were a function of the higher total dose
      received in the morbidly obese group. No differences in daptomycin volume of
      distribution (V), total clearance, renal clearance, or protein binding were noted
      between the two groups. Of TBW, FFW, or IBW, TBW provided the best correlation to
      V. In contrast, TBW overestimated GFR through creatinine clearance calculations
      using the Cockcroft-Gault equation. Use of IBW in the Cockcroft-Gault equation or
      use of the four-variable modification of diet in renal disease equation best
      estimated GFR in morbidly obese subjects. Further studies of daptomycin
      pharmacokinetics in morbidly obese patients with acute bacterial infections and
      impaired renal function are necessary to better predict appropriate dosage
      intervals.

PMID- 17548490
TI  - Rapid dissemination and diversity of CTX-M extended-spectrum beta-lactamase genes
      in commensal Escherichia coli isolates from healthy children from low-resource
      settings in Latin America.
AB  - A survey carried out in 2005 among members of a healthy population of children
      living in Bolivia and Peru revealed that fecal carriage of Escherichia coli
      strains resistant to expanded-spectrum cephalosporins was remarkably increased
      compared to that observed in the same settings in 2002 (1.7% in 2005 versus 0.1%
      in 2002). In this work, we demonstrated that this phenomenon was mainly related
      to the dissemination of CTX-M-type extended-spectrum beta-lactamase (ESBL)
      determinants among commensal E. coli strains. Of 50 ESBL-producing isolates
      collected in the 2005 survey, 44 harbored a CTX-M-type and 6 an SHV-type (SHV-2
      or SHV-12) ESBL. Compared to 2002 results, an increased diversity of CTX-M-type
      ESBLs was also observed: members of the CTX-M-1 group (CTX-M-15) emerged in
      Bolivia (where only CTX-M-2 was observed in 2002), while members of the CTX-M-9
      group (CTX-M-14 and CTX-M-24) emerged in Peru (where only CTX-M-15 and CTX-M-2
      were observed in 2002). A new CTX-M-2 variant named CTX-M-56 was also detected.
      Molecular characterization of the CTX-M-producing isolates and gene transfer
      experiments suggested that different mechanisms could be involved in the
      spreading of different CTX-M group determinants and revealed that additional
      resistance determinants for non-beta-lactam antibiotics were preferentially
      carried by plasmids encoding certain CTX-M variants (CTX-M-15 and variants of the
      CTX-M-2 group). Three CTX-M-15-encoding conjugative plasmids from Peruvian
      isolates carried the new fluoroquinolone resistance gene aac(6')-Ib-cr. To our
      best knowledge, this is the first report of the detection of aac(6')-Ib-cr in
      Latin America.

PMID- 17548491
TI  - Synergistic activity of dispersin B and cefamandole nafate in inhibition of
      staphylococcal biofilm growth on polyurethanes.
AB  - Antibiotic therapies to eradicate medical device-associated infections often fail
      because of the ability of sessile bacteria, encased in their exopolysaccharide
      matrix, to be more drug resistant than planktonic organisms. In the last two
      decades, several strategies to prevent microbial adhesion and biofilm formation
      on the surfaces of medical devices, based mainly on the use of antiadhesive,
      antiseptic, and antibiotic coatings on polymer surfaces, have been developed.
      More recent alternative approaches are based on molecules able to interfere with
      quorum-sensing phenomena or to dissolve biofilms. Interestingly, a newly purified
      beta-N-acetylglucosaminidase, dispersin B, produced by the gram-negative
      periodontal pathogen Actinobacillus actinomycetemcomitans, is able to dissolve
      mature biofilms produced by Staphylococcus epidermidis as well as some other
      bacterial species. Therefore, in this study, we developed new polymeric matrices
      able to bind dispersin B either alone or in combination with an antibiotic
      molecule, cefamandole nafate (CEF). We showed that our functionalized
      polyurethanes could adsorb a significant amount of dispersin B, which was able to
      exert its hydrolytic activity against the exopolysaccharide matrix produced by
      staphylococcal strains. When microbial biofilms were exposed to both dispersin B
      and CEF, a synergistic action became evident, thus characterizing these polymer
      dispersin B-antibiotic systems as promising, highly effective tools for
      preventing bacterial colonization of medical devices.

PMID- 17548492
TI  - Distribution of radioactivity in bone and related structures following
      administration of [14C]dalbavancin to New Zealand white rabbits.
AB  - Penetration of dalbavancin into noninfected bone and joint tissues was assessed
      after an intravenous dose of 20 mg/kg (of body weight) [(14)C]dalbavancin given
      to rabbits. Drug-derived radioactivity, determined over 14 days by either liquid
      scintillation counting or autoradiography, remained above the MIC for common gram
      positive pathogens that cause bone and joint infections.

PMID- 17548494
TI  - Cross-resistance to medical and agricultural azole drugs in yeasts from the
      oropharynx of human immunodeficiency virus patients and from environmental
      Bavarian vine grapes.
AB  - Cross-resistance among Candida albicans isolates from the oropharynges of human
      immunodeficiency virus-infected patients (n = 16) and environmental yeast strains
      of various species (n = 54) to medical and agricultural azole drugs was observed.
      Precautions against the unnecessary widespread use of azoles in the environment
      and human medicine are strongly recommended to prevent patients from acquiring
      azole-resistant yeasts.

PMID- 17548493
TI  - Modulation of the cellular accumulation and intracellular activity of daptomycin
      towards phagocytized Staphylococcus aureus by the P-glycoprotein (MDR1) efflux
      transporter in human THP-1 macrophages and madin-darby canine kidney cells.
AB  - P-glycoprotein (P-gp; MDR1), a major efflux transporter, recognizes various
      antibiotics and is present in macrophages. We have examined its effect on the
      modulation of the intracellular accumulation and activity of daptomycin towards
      phagocytized Staphylococcus aureus (ATCC 25923) in human THP-1 macrophages, in
      comparison with MDCK epithelial cells (wild type and MDCK-MDR1 overexpressing P
      gp; the bulk of the protein was immunodetected at the surface of all three cell
      types). Daptomycin displayed concentration-dependent intracellular activity (Hill
      equation pattern) in THP-1 and MDCK cells with (i) 50% effective drug
      extracellular concentration (EC(50); relative potency) and static concentrations
      at 9 to 10 times the MIC and (ii) maximal efficacy (E(max); CFU decrease at
      infinite extracellular drug concentration) at 1.6 to 2 log compared to that of
      the postphagocytosis inoculum. Verapamil (100 microM) and elacridar (GF 120918;
      0.5 microM), two known inhibitors of P-gp, decreased daptomycin EC(50) (about
      threefold) in THP-1 and MDCK cells without affecting E(max). Daptomycin EC(50)
      was about three- to fourfold higher and accumulation in MDCK-MDR1 commensurately
      lower than in wild-type cells. In THP-1 macrophages, (i) verapamil and ATP
      depletion increased, and ouabain (an inducer of mdr1 [the gene encoding P-gp]
      expression) decreased the accumulation of daptomycin in parallel with that of
      DiOC(2) (a known substrate of P-gp); (ii) silencing mdr1 with duplex human mdr1
      siRNAs reduced the cell content in immunoreactive P-gp to 15 to 30% of controls
      and caused an eight- to 13-fold increase in daptomycin accumulation. We conclude
      that daptomycin is subject to efflux from THP-1 macrophages and MDCK cells by P
      gp, which reduces its intracellular activity against phagocytized S. aureus.

PMID- 17548495
TI  - Susceptibility of Cryptococcus neoformans to photodynamic inactivation is
      associated with cell wall integrity.
AB  - Photodynamic therapy is a rapidly developing antimicrobial technology which
      combines a nontoxic photoactivatable dye or photosensitizer with harmless visible
      light of the correct wavelength to excite the dye to its reactive triplet state
      to generate reactive oxygen species toxic to cells. In this report we present
      evidence that the fungal pathogen Cryptococcus neoformans is susceptible to
      photodynamic inactivation by use of a polycationic conjugate of polyethyleneimine
      and the photosensitizer chlorin(e6). A C. neoformans rom2 mutant, with a mutation
      involving a putative Rho1 guanyl nucleotide exchange factor that is part of the
      protein kinase C-cell wall integrity pathway, demonstrated a compromised cell
      wall and less (1,3)beta-d glucan than the wild-type strain and increased
      accumulation of PEI-ce6 as assessed by fluorescence uptake and confocal
      microscopy. Interestingly, C. neoformans rom2 was hypersusceptible to
      photodynamic inactivation and coincubation of wild-type C. neoformans strain
      KN99alpha with caspofungin-enhanced photoinactivation. These studies demonstrated
      that C. neoformans is sensitive to photodynamic therapy and illustrated the
      significance of cell wall integrity in microbial susceptibility to antimicrobial
      photodynamic inactivation.

PMID- 17548496
TI  - Salicylidene acylhydrazides that affect type III protein secretion in Salmonella
      enterica serovar typhimurium.
AB  - A collection of nine salicylidene acylhydrazide compounds were tested for their
      ability to inhibit the activity of virulence-associated type III secretion
      systems (T3SSs) in Salmonella enterica serovar Typhimurium. The compounds
      strongly affected Salmonella pathogenicity island 1 (SPI1) T3SS-mediated invasion
      of epithelial cells and in vitro secretion of SPI1 invasion-associated effector
      proteins. The use of a SPI1 effector beta-lactamase fusion protein implicated
      intracellular entrapment of the protein construct upon application of a
      salicylidene acylhydrazide, whereas the use of chromosomal transcriptional gene
      fusions revealed a compound-mediated transcriptional silencing of SPI1.
      Salicylidene acylhydrazides also affected intracellular bacterial replication in
      murine macrophage-like cells and blocked the transport of an epitope-tagged SPI2
      effector protein. Two of the compounds significantly inhibited bacterial motility
      and expression of extracellular flagellin. We conclude that salicylidene
      acylhydrazides affect bacterial T3SS activity in S. enterica and hence could be
      used as lead substances when designing specific inhibitors of bacterial T3SSs in
      order to pharmaceutically intervene with bacterial virulence.

PMID- 17548497
TI  - Investigating Toll-like receptor agonists for potential to treat hepatitis C
      virus infection.
AB  - Toll-like receptors (TLRs) are key mediators of innate immunity, and their
      activation by microbial components leads to the production of cytokines and
      interferons. Recombinant alpha interferon has been used to treat several viral
      diseases and is the current standard of care for hepatitis C virus (HCV)
      infection. Recently, agonists of TLR7 and TLR9 have been shown to have clinical
      efficacy in HCV patients, and this is correlated with their ability to induce
      endogenous type I interferon production. We have carried out a comprehensive
      study of agonists of TLRs 1 to 9 to determine if any additional TLRs can induce
      antiviral molecules from human peripheral blood mononuclear cells (PBMCs). The
      agonists were incubated with PBMCs, and the supernatant was then removed and
      added to HCV replicon cells to assess antiviral activity. Agonists of TLRs 3, 4,
      7, 8, and 9 were found to be potent inducers of antiviral activity in PBMC
      supernatants, and the activity correlated with the induction of alpha interferon
      and the interferon-induced antiviral biomarker 2',5'-oligoadenylate synthase.
      Antiviral activity of TLR7 and TLR8 agonists was blocked by an antibody that
      binds to the type I interferon receptor, confirming that the antiviral activity
      results from type I interferon induction. TLR4 and TLR8 agonists were found to
      strongly induce the proinflammatory cytokines interleukin 1beta and tumor
      necrosis factor alpha at concentrations similar to those inducing antiviral
      activity. This raises concerns about adverse side effects if these were to be
      used as antiviral agents. We therefore conclude that TLRs 3, 7, and 9 represent
      the most attractive targets for the development of new HCV therapies.

PMID- 17548498
TI  - Activity against human immunodeficiency virus type 1, intracellular metabolism,
      and effects on human DNA polymerases of 4'-ethynyl-2-fluoro-2'-deoxyadenosine.
AB  - We examined the intracytoplasmic anabolism and kinetics of antiviral activity
      against human immunodeficiency virus type 1 (HIV-1) of a nucleoside reverse
      transcriptase inhibitor, 4'-ethynyl-2-fluoro-2'-deoxyadenosine (EFdA), which has
      potent activity against wild-type and multidrug-resistant HIV-1 strains. When CEM
      cells were exposed to 0.1 microM [(3)H]EFdA or [(3)H]3'-azido-2',3'
      dideoxythymidine (AZT) for 6 h, the intracellular EFdA-triphosphate (TP) level
      was 91.6 pmol/10(9) cells, while that of AZT was 396.5 pmol/10(9) cells. When CEM
      cells were exposed to 10 microM [(3)H]EFdA, the amount of EFdA-TP increased by 22
      fold (2,090 pmol/10(9) cells), while the amount of [(3)H]AZT-TP increased only
      moderately by 2.4-fold (970 pmol/10(9) cells). The intracellular half-life values
      of EFdA-TP and AZT-TP were approximately 17 and approximately 3 h, respectively.
      When MT-4 cells were cultured with 0.01 microM EFdA for 24 h, thoroughly washed
      to remove EFdA, further cultured without EFdA for various periods of time,
      exposed to HIV-1(NL4-3), and cultured for an additional 5 days, the protection
      values were 75 and 47%, respectively, after 24 and 48 h with no drug incubation,
      while those with 1 microM AZT were 55 and 9.2%, respectively. The 50% inhibitory
      concentration values of EFdA-TP against human polymerases alpha, beta, and gamma
      were >100 microM, >100 microM, and 10 microM, respectively, while those of ddA-TP
      were >100 microM, 0.2 microM, and 0.2 microM, respectively. These data warrant
      further development of EFdA as a potential therapeutic agent for those patients
      who harbor wild-type HIV-1 and/or multidrug-resistant variants.

PMID- 17548499
TI  - New plasmid-mediated fluoroquinolone efflux pump, QepA, found in an Escherichia
      coli clinical isolate.
AB  - Plasmid-mediated Qnr and AAC(6')-Ib-cr have been recognized as new molecular
      mechanisms affecting fluoroquinolone (FQ) resistance. C316, an Escherichia coli
      strain demonstrating resistance to various FQs, was isolated in Japan. Resistance
      to FQs was augmented in an E. coli CSH2 transconjugant, but PCR failed to detect
      qnr genes, suggesting the presence of novel plasmid-mediated FQ resistance
      mechanisms. Susceptibility tests, DNA manipulation, and analyses of the gene and
      its product were performed to characterize the genetic determinant. A novel FQ
      resistant gene, qepA, was identified in a plasmid, pHPA, of E. coli C316, and
      both qepA and rmtB genes were mediated by a probable transposable element flanked
      by two copies of IS26. Levels of resistance to norfloxacin, ciprofloxacin, and
      enrofloxacin were significantly elevated in E. coli transformants harboring qepA
      under AcrB-TolC-deficient conditions. QepA showed considerable similarities to
      transporters belonging to the 14-transmembrane-segment family of environmental
      actinomycetes. The effect of carbonyl cyanide m-chlorophenylhydrazone (CCCP) on
      accumulation of norfloxacin was assayed in a qepA-harboring E. coli transformant.
      The intracellular accumulation of norfloxacin was decreased in a qepA-expressing
      E. coli transformant, but this phenomenon was canceled by CCCP. The augmented FQ
      resistance level acquired by the probable intergeneric transfer of a gene
      encoding a major facilitator superfamily-type efflux pump from some environmental
      microbes to E. coli was first identified. Surveillance of the qepA-harboring
      clinical isolates should be encouraged to minimize further dissemination of the
      kind of plasmid-dependent FQ resistance determinants among pathogenic microbes.

PMID- 17548500
TI  - Extended -10 promoter in ISAba-1 upstream of blaOXA-23 from Acinetobacter
      baumannii.

PMID- 17548501
TI  - Evaluation of NAD(+) -dependent DNA ligase of mycobacteria as a potential target
      for antibiotics.
AB  - Mycobacteria contain genes for several DNA ligases, including ligA, which encodes
      a NAD(+)-dependent enzyme that has been postulated to be a target for novel
      antibacterial compounds. Using a homologous recombination system, direct evidence
      is presented that wild-type ligA cannot be deleted from the chromosome of
      Mycobacterium smegmatis. Deletions of native ligA in M. smegmatis could be
      obtained only after the integration of an extra copy of M. smegmatis or
      Mycobacterium tuberculosis ligA into the attB site of the chromosome, with
      expression controlled by chemically inducible promoters. The four ATP-dependent
      DNA ligases encoded by the M. smegmatis chromosome were unable to replace the
      function of LigA. Interestingly, the LigA protein from M. smegmatis could be
      substituted with the NAD(+)-dependent DNA ligase of Escherichia coli or the ATP
      dependent ligase of bacteriophage T4. The conditional mutant strains allowed the
      analysis of the effect of LigA depletion on the growth of M. smegmatis. The
      protein level of the conditional mutants was estimated by Western blot analysis
      using antibodies raised against LigA of M. tuberculosis. This revealed that a
      strong overproduction or depletion of LigA did not affect the growth or survival
      of mycobacteria under standard laboratory conditions. In conclusion, although
      NAD(+)-dependent DNA ligase is essential for mycobacterial viability, only low
      levels of protein are required for growth. These findings suggest that very
      efficient inhibition of enzyme activity would be required if NAD(+)-dependent DNA
      ligase is to be useful as an antibiotic target in mycobacteria. The strains
      developed here will provide useful tools for the evaluation of the efficacy of
      any appropriate compounds in mycobacteria.

PMID- 17548502
TI  - Pulmonary and cardiac cysticercosis: helical CT findings.
AB  - The authors aim to report the chest CT findings of a patient with disseminated
      cysticercosis, emphasising the pulmonary and cardiac features. The main finding
      consisted of multiple pulmonary, cardiac and chest wall nodules. The present case
      demonstrates that cysticercosis should be considered in the differential
      diagnosis of multiple pulmonary nodules, mainly in those patients with similar
      lesions in the cardiac muscle and/or in the chest wall.

PMID- 17548503
TI  - CT findings of pulmonary artery dissection.
AB  - Pulmonary artery dissection is a serious fatal complication of chronic pulmonary
      arterial hypertension, always occurring at the site of maximal dilatation of the
      artery. Diagnosis is made mainly at autopsy as many of these patients experience
      sudden death when the main pulmonary artery dissects into the pericardium,
      causing acute cardiac tamponade. To our knowledge, five reported cases have
      described CT imaging findings of acute pulmonary artery dissection in the
      literature.

PMID- 17548504
TI  - Search your heart for a cause of syncope!
AB  - A 66-year-old female presented to casualty with recurrent syncopal episodes and a
      history of ischaemic heart disease. Initial investigations did not provide a
      definitive diagnosis. Subsequent CT scanning identified a giant pseudoaneurysm of
      the left anterior descending coronary artery, which is the largest reported to
      date. We include a short discussion on current literature surrounding coronary
      artery pseudoaneurysmal disease.

PMID- 17548505
TI  - Impact of [18F]-fluorodeoxyglucose ([18F]-FDG) imaging in sarcoidosis:
      unsuspected neurosarcoidosis discovered by [18F]-FDG PET and early metabolic
      response to corticosteroid therapy.
AB  - A 46-year-old woman, with biopsy proven pulmonary sarcoidosis, was referred for
      an [18F]-FDG PET/CT scan that depicted multivisceral involvement and an unusual
      [18F]-FDG focus located in the pituitary fossa consistent with pituitary
      sarcoidosis. This was confirmed by decreased antidiuretic hormone blood levels
      and contrast-enhanced CT scan. This unsuspected neurosarcoidosis prompted
      corticosteroid therapy. A [18F]-FDG-PET/CT examination performed 10 weeks after
      initiation of treatment revealed complete recovery. It is suggested that the
      skull base should be included in the PET scanning of patients with sarcoidosis.
      [18F]-FDG imaging may be useful in the early evaluation of response to treatment.

PMID- 17548507
TI  - An unusual cause of knee pain.

PMID- 17548508
TI  - Scott Fraser: live action embryology. Interview by R Williams.
AB  - Using cutting-edge approaches to live imaging, Scott Fraser captures the dynamics
      of development.

PMID- 17548509
TI  - A novel cell response triggered by interphase centromere structural instability.
AB  - Interphase centromeres are crucial domains for the proper assembly of
      kinetochores at the onset of mitosis. However, it is not known whether the
      centromere structure is under tight control during interphase. This study uses
      the peculiar property of the infected cell protein 0 of herpes simplex virus type
      1 to induce centromeric structural damage, revealing a novel cell response
      triggered by centromere destabilization. It involves centromeric accumulation of
      the Cajal body-associated coilin and fibrillarin as well as the survival motor
      neuron proteins. The response, which we have termed interphase centromere damage
      response (iCDR), was observed in all tested human and mouse cells, indicative of
      a conserved mechanism. Knockdown cells for several constitutive centromere
      proteins have shown that the loss of centromeric protein B provokes the
      centromeric accumulation of coilin. We propose that the iCDR is part of a novel
      safeguard mechanism that is dedicated to maintaining interphase centromeres
      compatible with the correct assembly of kinetochores, microtubule binding, and
      completion of mitosis.

PMID- 17548510
TI  - Reciprocal inhibition between Pax7 and muscle regulatory factors modulates
      myogenic cell fate determination.
AB  - Postnatal growth and regeneration of skeletal muscle requires a population of
      resident myogenic precursors named satellite cells. The transcription factor Pax7
      is critical for satellite cell biogenesis and survival and has been also
      implicated in satellite cell self-renewal; however, the underlying molecular
      mechanisms remain unclear. Previously, we showed that Pax7 overexpression in
      adult primary myoblasts down-regulates MyoD and prevents myogenin induction,
      inhibiting myogenesis. We show that Pax7 prevents muscle differentiation
      independently of its transcriptional activity, affecting MyoD function.
      Conversely, myogenin directly affects Pax7 expression and may be critical for
      Pax7 down-regulation in differentiating cells. Our results provide evidence for a
      cross-inhibitory interaction between Pax7 and members of the muscle regulatory
      factor family. This could represent an additional mechanism for the control of
      satellite cell fate decisions resulting in proliferation, differentiation, and
      self-renewal, necessary for skeletal muscle maintenance and repair.

PMID- 17548511
TI  - Syndecan-2 induces filopodia and dendritic spine formation via the neurofibromin
      PKA-Ena/VASP pathway.
AB  - Syndecan-2 induced filopodia before spinogenesis; therefore, filopodia formation
      was used here as a model to study the early downstream signaling of syndecan-2
      that leads to spinogenesis. Screening using kinase inhibitors indicated that
      protein kinase A (PKA) is required for syndecan-2-induced filopodia formation in
      both human embryonic kidney cells and hippocampal neurons. Because neurofibromin,
      a syndecan-2-binding partner, activates the cyclic adenosine monophosphate
      pathway, the role of neurofibromin in syndecan-2-induced filopodia formation was
      investigated by deletion mutant analysis, RNA interference, and dominant-negative
      mutant. The results showed that neurofibromin mediates the syndecan-2 signal to
      PKA. Among actin-associated proteins, Enabled (Ena)/vasodilator-stimulated
      phosphoprotein (VASP) were predicted as PKA effectors downstream of syndecan-2,
      as Ena/VASP, which is activated by PKA, induces actin polymerization. Indeed,
      when the activities of Ena/VASP were blocked, syndecan-2 no longer induced
      filopodia formation. Finally, in addition to filopodia formation, neurofibromin
      and Ena/VASP contributed to spinogenesis. This study reveals a novel signaling
      pathway in which syndecan-2 activates PKA via neurofibromin and PKA consequently
      phosphorylates Ena/VASP, promoting filopodia and spine formation.

PMID- 17548512
TI  - The Ig cell adhesion molecule Basigin controls compartmentalization and vesicle
      release at Drosophila melanogaster synapses.
AB  - Synapses can undergo rapid changes in size as well as in their vesicle release
      function during both plasticity processes and development. This fundamental
      property of neuronal cells requires the coordinated rearrangement of synaptic
      membranes and their associated cytoskeleton, yet remarkably little is known of
      how this coupling is achieved. In a GFP exon-trap screen, we identified
      Drosophila melanogaster Basigin (Bsg) as an immunoglobulin domain-containing
      transmembrane protein accumulating at periactive zones of neuromuscular
      junctions. Bsg is required pre- and postsynaptically to restrict synaptic bouton
      size, its juxtamembrane cytoplasmic residues being important for that function.
      Bsg controls different aspects of synaptic structure, including distribution of
      synaptic vesicles and organization of the presynaptic cortical actin
      cytoskeleton. Strikingly, bsg function is also required specifically within the
      presynaptic terminal to inhibit nonsynchronized evoked vesicle release. We thus
      propose that Bsg is part of a transsynaptic complex regulating synaptic
      compartmentalization and strength, and coordinating plasma membrane and cortical
      organization.

PMID- 17548513
TI  - Nodes of Ranvier and axon initial segments are ankyrin G-dependent domains that
      assemble by distinct mechanisms.
AB  - Axon initial segments (AISs) and nodes of Ranvier are sites of action potential
      generation and propagation, respectively. Both domains are enriched in sodium
      channels complexed with adhesion molecules (neurofascin [NF] 186 and NrCAM) and
      cytoskeletal proteins (ankyrin G and betaIV spectrin). We show that the AIS and
      peripheral nervous system (PNS) nodes both require ankyrin G but assemble by
      distinct mechanisms. The AIS is intrinsically specified; it forms independent of
      NF186, which is targeted to this site via intracellular interactions that require
      ankyrin G. In contrast, NF186 is targeted to the node, and independently cleared
      from the internode, by interactions of its ectodomain with myelinating Schwann
      cells. NF186 is critical for and initiates PNS node assembly by recruiting
      ankyrin G, which is required for the localization of sodium channels and the
      entire nodal complex. Thus, initial segments assemble from the inside out driven
      by the intrinsic accumulation of ankyrin G, whereas PNS nodes assemble from the
      outside in, specified by Schwann cells, which direct the NF186-dependent
      recruitment of ankyrin G.

PMID- 17548514
TI  - Alpha4beta1 integrin and erythropoietin mediate temporally distinct steps in
      erythropoiesis: integrins in red cell development.
AB  - Erythropoietin (Epo) is essential for the terminal proliferation and
      differentiation of erythroid progenitor cells. Fibronectin is an important part
      of the erythroid niche, but its precise role in erythropoiesis is unknown. By
      culturing fetal liver erythroid progenitors, we show that fibronectin and Epo
      regulate erythroid proliferation in temporally distinct steps: an early Epo
      dependent phase is followed by a fibronectin-dependent phase. In each phase, Epo
      and fibronectin promote expansion by preventing apoptosis partly through bcl-xL.
      We show that alpha(4), alpha(5), and beta(1) are the principal integrins
      expressed on erythroid progenitors; their down-regulation during erythropoiesis
      parallels the loss of cell adhesion to fibronectin. Culturing erythroid
      progenitors on recombinant fibronectin fragments revealed that only substrates
      that engage alpha(4)beta(1)-integrin support normal proliferation. Collectively,
      these data suggest a two-phase model for growth factor and extracellular matrix
      regulation of erythropoiesis, with an early Epo-dependent, integrin-independent
      phase followed by an Epo-independent, alpha(4)beta(1)-integrin-dependent phase.

PMID- 17548515
TI  - Contact-dependent inhibition of EGFR signaling by Nf2/Merlin.
AB  - The neurofibromatosis type 2 (NF2) tumor suppressor, Merlin, is a
      membrane/cytoskeleton-associated protein that mediates contact-dependent
      inhibition of proliferation. Here we show that upon cell-cell contact Merlin
      coordinates the processes of adherens junction stabilization and negative
      regulation of epidermal growth factor receptor (EGFR) signaling by restraining
      the EGFR into a membrane compartment from which it can neither signal nor be
      internalized. In confluent Nf2(-/-) cells, EGFR activation persists, driving
      continued proliferation that is halted by specific EGFR inhibitors. These studies
      define a new mechanism of tumor suppression, provide mechanistic insight into the
      poorly understood phenomenon of contact-dependent inhibition of proliferation,
      and suggest a therapeutic strategy for NF2-mutant tumors.

PMID- 17548516
TI  - uPAR-induced cell adhesion and migration: vitronectin provides the key.
AB  - Expression of the membrane receptor uPAR induces profound changes in cell
      morphology and migration, and its expression correlates with the malignant
      phenotype of cancers. To identify the molecular interactions essential for uPAR
      function in these processes, we carried out a complete functional alanine scan of
      uPAR in HEK293 cells. Of the 255 mutant receptors characterized, 34 failed to
      induce changes in cell morphology. Remarkably, the molecular defect of all of
      these mutants was a specific reduction in integrin-independent cell binding to
      vitronectin. A membrane-tethered plasminogen activator inhibitor-1, which has the
      same binding site in vitronectin as uPAR, replicated uPAR-induced changes. A
      direct uPAR-vitronectin interaction is thus both required and sufficient to
      initiate downstream changes in cell morphology, migration, and signal
      transduction. Collectively these data demonstrate a novel mechanism by which a
      cell adhesion molecule lacking inherent signaling capability evokes complex
      cellular responses by modulating the contact between the cell and the matrix
      without the requirement for direct lateral protein-protein interactions.

PMID- 17548517
TI  - Zoonotic orthopoxviruses encode a high-affinity antagonist of NKG2D.
AB  - NK and T lymphocytes express both activating and inhibiting receptors for various
      members of the major histocompatibility complex class I superfamily (MHCISF). To
      evade immunologic cytotoxicity, many viruses interfere with the function of these
      receptors, generally by altering the displayed profile of MHCISF proteins on host
      cells. Using a structurally constrained hidden Markov model, we discovered an
      orthopoxvirus protein, itself distantly class I-like, that acts as a competitive
      antagonist of the NKG2D activating receptor. This orthopoxvirus MHC class I-like
      protein (OMCP) is conserved among cowpox and monkeypox viruses, secreted by
      infected cells, and bound with high affinity by NKG2D of rodents and humans (K(D)
      approximately 30 and 0.2 nM, respectively). OMCP blocks recognition of host
      encoded ligands and inhibits NKG2D-dependent killing by NK cells. This finding
      represents a novel mechanism for viral interference with NKG2D and sheds light on
      intercellular recognition events underlying innate immunity against emerging
      orthopoxviruses.

PMID- 17548518
TI  - CCR4-dependent regulatory T cell function in inflammatory bowel disease.
AB  - Inflammatory bowel disease (IBD) is an idiopathic inflammatory disease of the
      intestine. CD4(+) T lymphocytes play an important role in both initiating and
      regulating intestinal inflammatory immune responses. CD4(+)CD25(+)CD45RB(low)
      regulatory T (T reg) cells are capable of preventing the development of colitis
      in a mouse model of IBD. The precise mechanism of T reg cell-mediated prevention
      of colitis in this model is unclear, and the role of chemokine receptors in the
      trafficking and function of T reg cells in this model has not been determined. We
      examined the role of the chemokine receptor CCR4 in in vivo trafficking and
      suppressive function of T reg cells in a mouse adoptive transfer model of IBD.
      CCR4-deficient T reg cells failed to accumulate in the mesenteric lymph nodes
      (MLNs) at early time points (2-5 d) after adoptive transfer, resulting in a
      failure to suppress the generation of pathogenic T cells and the development of
      colitis. Moreover, although CCR4-deficent T cells had equivalent in vitro
      suppressive activity and accumulated in MLNs at later time points (42-56 d), they
      were unable to suppress colitis. Our study demonstrates that CCR4 plays an
      important role in T reg cell trafficking in LNs and that this is critical for T
      reg cell suppressive function in vivo.

PMID- 17548519
TI  - MyD88-dependent expansion of an immature GR-1(+)CD11b(+) population induces T
      cell suppression and Th2 polarization in sepsis.
AB  - Polymicrobial sepsis alters the adaptive immune response and induces T cell
      suppression and Th2 immune polarization. We identify a GR-1(+)CD11b(+) population
      whose numbers dramatically increase and remain elevated in the spleen, lymph
      nodes, and bone marrow during polymicrobial sepsis. Phenotypically, these cells
      are heterogeneous, immature, predominantly myeloid progenitors that express
      interleukin 10 and several other cytokines and chemokines. Splenic GR-1(+) cells
      effectively suppress antigen-specific CD8(+) T cell interferon (IFN) gamma
      production but only modestly suppress antigen-specific and nonspecific CD4(+) T
      cell proliferation. GR-1(+) cell depletion in vivo prevents both the sepsis
      induced augmentation of Th2 cell-dependent and depression of Th1 cell-dependent
      antibody production. Signaling through MyD88, but not Toll-like receptor 4, TIR
      domain-containing adaptor-inducing IFN-beta, or the IFN-alpha/beta receptor, is
      required for complete GR-1(+)CD11b(+) expansion. GR-1(+)CD11b(+) cells contribute
      to sepsis-induced T cell suppression and preferential Th2 polarization.

PMID- 17548520
TI  - Deubiquitinating enzyme CYLD negatively regulates the ubiquitin-dependent kinase
      Tak1 and prevents abnormal T cell responses.
AB  - The deubiquitinating enzyme CYLD has recently been implicated in the regulation
      of signal transduction, but its physiological function and mechanism of action
      are still elusive. In this study, we show that CYLD plays a pivotal role in
      regulating T cell activation and homeostasis. T cells derived from Cyld knockout
      mice display a hyperresponsive phenotype and mediate the spontaneous development
      of intestinal inflammation. Interestingly, CYLD targets a ubiquitin-dependent
      kinase, transforming growth factor-beta-activated kinase 1 (Tak1), and inhibits
      its ubiquitination and autoactivation. Cyld-deficient T cells exhibit
      constitutively active Tak1 and its downstream kinases c-Jun N-terminal kinase and
      IkappaB kinase beta. These results emphasize a critical role for CYLD in
      preventing spontaneous activation of the Tak1 axis of T cell signaling and,
      thereby, maintaining normal T cell function.

PMID- 17548521
TI  - Altering the distribution of Foxp3(+) regulatory T cells results in tissue
      specific inflammatory disease.
AB  - CD4(+)Foxp3(+) regulatory T cells (T reg) are essential for maintaining self
      tolerance, but their functional mechanisms and sites of action in vivo are poorly
      defined. We examined the homing receptor expression and tissue distribution of T
      reg cells in the steady state and determined whether altering their distribution
      by removal of a single chemokine receptor impairs their ability to maintain
      tissue-specific peripheral tolerance. We found that T reg cells are distributed
      throughout all nonlymphoid tissues tested, and are particularly prevalent in the
      skin, where they express a unique CCR4(+)CD103(hi) phenotype. T reg cell
      expression of CCR4 and CD103 is induced by antigen-driven activation within
      subcutaneous lymph nodes, and accumulation of T reg cells in the skin and lung
      airways is impaired in the absence of CCR4 expression. Mice with a complete loss
      of CCR4 in the T reg cell compartment develop lymphocytic infiltration and severe
      inflammatory disease in the skin and lungs, accompanied by peripheral
      lymphadenopathy and increased differentiation of skin-tropic CD4(+)Foxp3(+) T
      cells. Thus, selectively altering T reg cell distribution in vivo leads to the
      development of tissue-specific inflammatory disease.

PMID- 17548523
TI  - A novel inhibitor of the alternative pathway of complement reverses inflammation
      and bone destruction in experimental arthritis.
AB  - Complement is an important component of the innate and adaptive immune response,
      yet complement split products generated through activation of each of the three
      complement pathways (classical, alternative, and lectin) can cause inflammation
      and tissue destruction. Previous studies have shown that complement activation
      through the alternative, but not classical, pathway is required to initiate
      antibody-induced arthritis in mice, but it is unclear if the alternative pathway
      (AP) plays a role in established disease. Previously, we have shown that human
      complement receptor of the immunoglobulin superfamily (CRIg) is a selective
      inhibitor of the AP of complement. Here, we present the crystal structure of
      murine CRIg and, using mutants, provide evidence that the structural requirements
      for inhibition of the AP are conserved in human and mouse. A soluble form of CRIg
      reversed inflammation and bone loss in two experimental models of arthritis by
      inhibiting the AP of complement in the joint. Our data indicate that the AP of
      complement is not only required for disease induction, but also disease
      progression. The extracellular domain of CRIg thus provides a novel tool to study
      the effects of inhibiting the AP of complement in established disease and
      constitutes a promising therapeutic with selectivity for a single complement
      pathway.

PMID- 17548522
TI  - Dendritic cell quiescence during systemic inflammation driven by LPS stimulation
      of radioresistant cells in vivo.
AB  - Dendritic cell (DC) activation is a prerequisite for T cell priming. During
      infection, activation can ensue from signaling via pattern-recognition receptors
      after contact with pathogens or infected cells. Alternatively, it has been
      proposed that DCs can be activated indirectly by signals produced by infected
      tissues. To address the contribution of tissue-derived signals, we measured DC
      activation in a model in which radioresistant cells can or cannot respond to
      lipopolysaccharide (LPS). We report that recognition of LPS by the radioresistant
      compartment is sufficient to induce local and systemic inflammation characterized
      by high circulating levels of tumor necrosis factor (TNF) alpha, interleukin (IL)
      1beta, IL-6, and CC chemokine ligand 2. However, this is not sufficient to
      activate DCs, whether measured by migration, gene expression, phenotypic, or
      functional criteria, or to render DC refractory to subsequent stimulation with
      CpG-containing DNA. Similarly, acute or chronic exposure to proinflammatory
      cytokines such as TNF-alpha +/- interferon alpha/beta has marginal effects on DC
      phenotype in vivo when compared with LPS. In addition, DC activation and
      migration induced by LPS is unimpaired when radioresistant cells cannot respond
      to the stimulus. Thus, inflammatory mediators originating from nonhematopoietic
      tissues and from radioresistant hematopoietic cells are neither sufficient nor
      required for DC activation in vivo.

PMID- 17548524
TI  - Complement factor H and the hemolytic uremic syndrome.
AB  - Immune recognition is coupled to powerful proinflammatory effector pathways that
      must be tightly regulated. The ancient alternative pathway of complement
      activation is one such proinflammatory pathway. Genetic susceptibility factors
      have been identified in both regulators and activating components of the
      alternative pathway that are associated with thrombotic microangiopathies,
      glomerulonephritides, and chronic conditions featuring debris deposition. These
      observations indicate that excessive alternative pathway activation promotes
      thrombosis in the microvasculature and tissue damage during debris accumulation.
      Intriguingly, distinct genetic changes in factor H (FH), a key regulator of the
      alternative pathway, are associated with hemolytic uremic syndrome (HUS),
      membranoproliferative glomerulonephritis (dense deposit disease), or age-related
      macular degeneration (AMD). A mouse model of HUS designed to mirror human
      mutations in FH has now been developed, providing new understanding of the
      molecular pathogenesis of complement-related endothelial disorders.

PMID- 17548525
TI  - The role of information-processing capacity and goals in attitude-congruent
      selective exposure effects.
AB  - Two experiments explored the role of information-processing capacity and
      strategies in regulating attitude-congruent selective exposure. In Experiment 1,
      participants were placed under time pressure and randomly assigned to conditions
      in which either an attitude-expressive or no-information processing goal was made
      salient. Analyses revealed an attitude-congruent selective exposure effect and
      indicated that this effect was stronger when an attitude-expressive goal was made
      salient than when no goal was made salient. In Experiment 2, information
      processing goals and time pressure were factorially manipulated. Analyses
      revealed an attitude-congruent selective exposure effect and indicated that this
      effect was especially strong when time pressure was high and an attitude
      expressive goal was made salient. In both experiments, bias at exposure was found
      to predict bias at later stages of information processing (attention and memory).
      Supplementary analyses and data confirmed that the attitude-expressive goal
      manipulation activated its intended motivational processing strategy.

PMID- 17548526
TI  - Rash and desquamating skin in a neonate.

PMID- 17548527
TI  - Chest pain. Hemothorax.

PMID- 17548529
TI  - Distribution of neurocalcin-containing neurons reveals sexual dimorphism in the
      mouse olfactory bulb.
AB  - Olfactory sexual dimorphism has mainly been described in the vomeronasal system,
      in relation to reproductive behavior, while evidence of sexual dimorphism in the
      main olfactory bulb (OB) remains scarce. There are no data indicating sex-related
      differences in the neurochemistry of intrinsic olfactory elements. Neurocalcin
      (NC) is a calcium-binding protein that is expressed in specific neuronal
      populations of the central nervous system. Here we analyzed by
      immunohistochemistry the NC-containing neurons in the mouse main OB, comparing
      both their quantities and their locations between male and female animals. NC
      cell density was higher in males than in females in specific locations of the
      glomerular layer, the external plexiform layer, the mitral cell layer, and the
      internal plexiform layer. This divergence in the numbers of NC cells was
      especially patent in central rostrocaudal levels. The NC-containing neurons
      exhibiting sexual divergence were identified as both juxtaglomerular and short
      axon cells. This is the first description of sexual dimorphism regarding neurons
      belonging to the mouse main OB. According to their distribution in the OB,
      neurocalcin-immunoreactive interneurons could reflect a sexually dimorphic
      regulation of specific odorants.

PMID- 17548528
TI  - Transcription factor binding to a putative double E-box motif represses CYP3A4
      expression in human lung cells.
AB  - Two vital enzymes of the CYP3A subfamily, CYP3A4 and CYP3A5, are differentially
      expressed in the human lung. However, the molecular mechanisms that regulate
      tissue-selective expression of the genes are poorly understood. The ability of
      the 5' upstream promoter region of these two genes to drive luciferase reporter
      activities in human lung A549 cells was dramatically different. The CYP3A5
      promoter region activated luciferase gene expression by 10-fold over the
      promoterless construct, whereas the CYP3A4 promoter did not drive expression.
      Sequence comparisons of the promoters identified a 57-base pair insertion in the
      CYP3A4 promoter region (-71 to -127) that was absent in the CYP3A5 promoter.
      Deletion of the 57-bp motif from CYP3A4 or insertion into the CYP3A5 promoter,
      showed that this motif represses CYP3A4 expression in lung. EMSA analysis using
      nuclear extracts from either A549 cells or human lung tissues showed two specific
      protein/DNA complexes formed with the (32)P-labeled CYP3A4 57-bp oligonucleotide.
      EMSA analyses identified two E-box motifs as the minimal specific cis-elements.
      Supershift assays with antibodies directed against known double- or single-E-box
      binding factors (TAL1, deltaEF1, E2A, HEB, etc.) failed to identify this factor
      as a previously characterized trans-acting double E-box binding protein. These
      results demonstrated that the 5'-upstream region of CYP3A4 contains an active
      putative double E-box repressor motif, not present in the 5'-upstream region of
      the CYP3A5 gene, that attenuates CYP3A4 expression in the human lung. We believe
      that this is the first documented case in which a cytochrome P450 gene is
      actively repressed in a tissue-specific manner.

PMID- 17548530
TI  - Kidney tissue reconstruction by fetal kidney cell transplantation: effect of
      gestation stage of fetal kidney cells.
AB  - Dialysis and kidney transplantation, current therapies for kidney failure, have
      limitations such as severe complications, donor shortage, and immune-related
      problems. The development of an alternative treatment for kidney failure is
      demanded. The present study shows that the transplantation of fetal kidney cells
      reconstitutes functional kidney tissue, and that the gestation stage of kidney
      cells influences the kidney reconstitution. Fetal kidney cells were isolated from
      metanephroi of rat fetuses at various gestation stages and transplanted into the
      omentum or kidney of immunodeficient mice. Immunophenotype analysis of fetal
      kidney cells showed apparent expression of stem cell markers. Three weeks after
      transplantation, histological analyses of retrieved grafts revealed the formation
      of kidney structures, including fluorescently labeled transplanted cells,
      suggesting the potential of fetal kidney cells to reconstitute kidney tissues.
      The grafts retrieved from omentum contained cystic fluids with concentrated
      solutes. However, transplanted early fetal kidney cells had also differentiated
      into nonrenal tissues such as bone and cartilage. In addition, transplantation of
      fetal kidney cells from a later gestation stage resulted in poor kidney structure
      formation. Kidney-specific genes were strongly expressed in the earlier cell
      transplants. The cells at an earlier gestation stage had higher colony forming
      ability than the cells at a later stage. This study demonstrates the
      reconstitution of kidney tissue by transplanting fetal kidney cells and the
      presence of an optimal time window in which fetal kidney cells regenerate kidney
      tissues. Disclosure of potential conflicts of interest is found at the end of
      this article.

PMID- 17548531
TI  - Atrial-radiofrequency catheter ablation mediated targeting of mesenchymal stromal
      cells.
AB  - Sinus node dysfunction and high-degree heart block are the major causes for
      electronic pacemaker implantation. Recently, genetically modified mesenchymal
      stromal cells (MSCs, also known as "mesenchymal stem cells") were demonstrated to
      generate pacemaker function in vivo. However, experimental approaches typically
      use open thoracotomy for direct cell injection into the myocardium. Future
      clinical implementation, however, essentially requires development of more gentle
      methods to precisely and efficiently apply specified stem cells at specific
      cardiac locations. In a "proof of concept" study, we performed selective power
      controlled radiofrequency catheter ablation (RFCA) with eight ablation pulses (30
      W, 60 seconds each) to induce heat-mediated lesions at the auricles of the
      cardiac right atrium of four healthy foxhounds. The next day, allogeneic MSCs
      (4.3 x 10(5) cells per kilogram of body weight) labeled with superparamagnetic
      iron oxide particles (SPIOs) were infused intravenously. Hearts were explanted 8
      days later. High numbers of SPIO-labeled cells were identified in areas
      surrounding the RFCA-induced lesions by Prussian blue staining. Antibody staining
      revealed SPIO-labeled cells being positive for the typical MSC surface antigen
      CD44. In contrast, low levels of calprotectin, an antigen found on monocytes and
      macrophages, indicated negligible infiltration of monocytes in MSC-positive
      areas. Thus, RFCA allows targeting of MSCs to the cardiac right atrium, adjacent
      to the sinoatrial node, providing an opportunity to rescue or generate pacemaker
      function without open thoracotomy and direct injection of MSCs. This method
      presents a new strategy for cardiac stem cell application leading to an efficient
      guidance of MSCs into the myocardium. Disclosure of potential conflicts of
      interest is found at the end of this article.

PMID- 17548532
TI  - Creating an immune-privileged site using retinal progenitor cells and
      biodegradable polymers.
AB  - We describe the creation of local immune privilege (IP) using retinal progenitor
      cells (RPCs) and biodegradable polymers. Murine RPCs were seeded on poly(lactic
      coglycolic acid) polymers to generate composite grafts. Composites or RPCs alone
      were transplanted into allogeneic kidney capsules. Grafts survived at all time
      points, differentiating into neurons and astrocytes. Upon treatment with
      interferon gamma (IFNgamma), major histocompatibility complex antigens were
      upregulated. Although 10% of IFNgamma-treated RPC grafts survived 14 days, 66% of
      the IFNgamma-treated composites survived in part by producing immune suppressive
      factors transforming growth factor-beta2, Fas ligand, and indoleamine 2,3
      dioxygenase. The composites were assayed for delayed-type hypersensitivity (DTH)
      by seeding composites with antigen-presenting cells incubated with ovalbumin.
      This resulted in suppression of ovalbumin-specific DTH, indicating that composite
      grafts consisting of biodegradable polymers and central nervous system progenitor
      cells can be used to generate local IP. This technology may be used to promote
      the survival of nonprivileged grafts (e.g., pancreas, liver, or skin). Disclosure
      of potential conflicts of interest is found at the end of this article.

PMID- 17548533
TI  - Chronic, intermittent exposure to chlorpyrifos in rats: protracted effects on
      axonal transport, neurotrophin receptors, cholinergic markers, and information
      processing.
AB  - Persistent behavioral abnormalities have been commonly associated with acute
      organophosphate (OP) pesticide poisoning; however, relatively little is known
      about the consequences of chronic OP exposures that are not associated with acute
      cholinergic symptoms. In this study, the behavioral and neurochemical effects of
      chronic, intermittent, and subthreshold exposures to the OP pesticide,
      chlorpyrifos (CPF), were investigated. Rats were injected with CPF s.c. (dose
      range, 2.5-18.0 mg/kg) every other day over the course of 30 days and then were
      given a 2-week CPF-free washout period. In behavioral experiments conducted
      during the washout period, dose-dependent decrements in a water-maze hidden
      platform task and a prepulse inhibition procedure were observed, without
      significant effects on open-field activity, Rotorod performance, grip strength,
      or a spontaneous novel object recognition task. After washout, levels of CPF and
      its metabolite 3,5,6-trichloro-2-pyridinol were minimal in plasma and brain;
      however, cholinesterase inhibition was still detectable. Furthermore, the 18.0
      mg/kg dose of CPF was associated with (brain region-dependent) decreases in nerve
      growth factor receptors and cholinergic proteins including the vesicular
      acetylcholine transporter, the high-affinity choline transporter, and the
      alpha(7)-nicotinic acetylcholine receptor. These deficits were accompanied by
      decreases in anterograde and retrograde axonal transport measured in sciatic
      nerves ex vivo. Thus, low-level (intermittent) exposure to CPF has persistent
      effects on neurotrophin receptors and cholinergic proteins, possibly through
      inhibition of fast axonal transport. Such neurochemical changes may lead to
      deficits in information processing and cognitive function.

PMID- 17548534
TI  - Atorvastatin treatment and vaccination efficacy.

PMID- 17548535
TI  - Experiential avoidance as a mediator of relationships between cognitions and hair
      pulling severity.
AB  - Cognitive-behavioral models suggest that certain cognitions and beliefs are
      functionally related to hair pulling in persons with trichotillomania (TTM), but
      little empirical data have been collected to test such claims. This study
      assessed dysfunctional beliefs about appearance, shameful cognitions, and fear of
      negative evaluation and their relation to hair-pulling severity in a sample of
      individuals self-reporting a diagnosis of TTM. Results showed significant
      correlations between these cognitions and hair-pulling severity; however,
      relations diminished or disappeared when controlling for experiential avoidance,
      a tendency to avoid or escape from unwanted private events. These findings
      suggest that treatments targeting cognitions may benefit from focusing on
      experiential avoidance more broadly.

PMID- 17548536
TI  - The effects of verbal instruction, modeling, rehearsal, and feedback on correct
      posture during flute playing.
AB  - A behavioral skills training package, including verbal instruction, modeling,
      rehearsal, and feedback, was used to teach children correct posture, defined as
      keeping feet on the floor, legs parallel to each other, and the back and neck
      perpendicular to the floor, during flute lessons. Three typically developing
      girls aged 8 to 9 years participated. All three students' posture improved from
      0% during baseline to nearly 100% after training for all sessions, generalization
      probes, and after a 1- to 2-month follow-up. The training package was proven
      effective in the acquisition, generalization, and maintenance of correct posture
      for flute playing.

PMID- 17548537
TI  - Applying acceptance, mindfulness, and values to the reduction of prejudice: a
      pilot study.
AB  - Two classroom approaches to reducing racial and ethnic prejudice among college
      students were compared: a class session based on acceptance and commitment
      therapy (ACT) and an educational lecture drawn from a textbook on the psychology
      of racial differences. Undergraduates who were enrolled in two separate classes
      on racial differences were exposed to each approach in a counterbalanced order.
      Results indicate that only the ACT intervention was effective in increasing
      positive behavioral intentions at post and a 1-week follow-up. These changes were
      associated with other self-reported changes that fit with the ACT model.
      Implications of a potentially new model of prejudice are briefly discussed.

PMID- 17548538
TI  - An empirical investigation of time-out with and without escape extinction to
      treat escape-maintained noncompliance.
AB  - The present study evaluates the effectiveness of two time-out (TO) procedures in
      reducing escape-maintained noncompliance of 4 children. Noncompliant behavioral
      function was established via a functional assessment (FA), including indirect and
      direct descriptive procedures and brief confirmatory experimental analyses.
      Following FA, parents were taught to consequate noncompliance with two different
      TO procedures, one without and one with escape extinction following TO release.
      Although results indicate TO without escape extinction is effective in increasing
      compliance above baseline levels, more optimal levels of compliance were obtained
      for all 4 children when escape extinction was added to the TO procedures already
      in place. Results indicate efficacy of TO with escape extinction when applied to
      escape-maintained noncompliance and are discussed as an initial example of the
      successful application of TO to behaviors maintained by negative reinforcement.

PMID- 17548539
TI  - Are parental gender role beliefs a predictor of change in sexual communication in
      a prevention program?
AB  - This study examined if pre-intervention maternal gender role beliefs predict
      change in sexual communication in a sexual risk behavior prevention program
      designed to increase parent-pre-adolescent communication about sex. A sample of
      281 African American fourth and fifth graders and their mothers participated in
      the five-session program and completed computerized questionnaires at baseline,
      postintervention, and 6-month follow-up. Based on mother report, more egalitarian
      maternal gender role beliefs predicted greater increases in parent-pre-adolescent
      communication about sex at postintervention. Based on pre-adolescent report,
      similar findings emerged at the 6-month follow-up, but only for boys. The
      relationship of maternal gender role beliefs to changes in sexual communication
      was not accounted for by maternal comfort with sexual communication with their
      pre-adolescents. The implications of maternal gender role beliefs in a prevention
      program designed to increase communication about sexual topics are considered.

PMID- 17548540
TI  - Effects of verbal and graphic performance feedback on behavior support plan
      implementation in a public elementary school.
AB  - Previous research suggests that performance feedback improves treatment
      integrity. This study compared the effects of verbal performance feedback and
      verbal plus graphic performance feedback on implementation of a student-specific
      behavior support plan (BSP) by members of a second-grade teaching team at a
      public elementary school. A consultant to the school delivered feedback following
      regularly scheduled classroom observations. Results indicated that combining
      verbal and graphic performance feedback was more effective than verbal
      performance feedback alone in improving treatment integrity. Informal data
      collected on student performance also suggested that appropriate behavior
      increased with better implementation of the BSP. Clinical and research issues are
      discussed.

PMID- 17548541
TI  - Incorporating "motivation" into the functional analysis of challenging behavior:
      on the interactive and integrative potential of the motivating operation.
AB  - Sensitivity theory attempts to account for the variability often observed in
      challenging behavior by recourse to the "aberrant motivation" of people with
      intellectual and developmental disabilities. In this article, we suggest that a
      functional analysis based on environmental (challenging environments) and
      biological (challenging needs) motivating operations provides a more parsimonious
      and empirically grounded account of challenging behavior than that proposed by
      sensitivity theory. It is argued that the concept of the motivating operation
      provides a means of integrating diverse strands of research without the undue
      inference of mentalistic constructs. An integrated model of challenging behavior
      is proposed, one that remains compatible with the central tenets of functional
      analysis.

PMID- 17548542
TI  - The impact of CBT and ACT models using psychology trainee therapists: a
      preliminary controlled effectiveness trial.
AB  - The present study compares the impact of individualized treatment provided by
      trainee therapists based on a traditional cognitive behavior therapy (CBT) and
      acceptance and commitment therapy (ACT) model. Fourteen therapists were given
      initial training in CBT and ACT. Outpatients (N = 28) were randomized to either
      approach, with each therapist treating one client within each model, linked to a
      functional analysis. Clients treated within an ACT model showed better symptom
      improvement than the CBT clients, despite the fact that students felt initially
      less knowledgeable about ACT and were more fearful throughout when it was used.
      CBT improved client self-confidence more rapidly than ACT, and ACT improved
      acceptance more than CBT. Both processes predicted better outcomes; acceptance
      remained predictive when controlling for self-confidence but not vice versa.
      Overall, therapists with limited training in both models got better results with
      ACT and the processes of change fit with the ACT model.

PMID- 17548543
TI  - The impact of written exposure on worry: a preliminary investigation.
AB  - The main goal of this study was to examine the effect of written exposure on
      generalized anxiety disorder (GAD)-related symptoms in high worriers. Thirty
      nonclinical high worriers were randomly assigned to either a written exposure
      condition or a control writing condition. Self-report measures were used to
      assess worry, GAD somatic symptoms, depression, and intolerance of uncertainty at
      four time points during the study. Using hierarchical linear modeling (HLM), the
      authors found that all symptoms (i.e., worry, GAD somatic symptoms, and
      depression) significantly decreased over time in the written exposure group
      (although GAD somatic symptoms also decreased in the control group). Moreover,
      consistent with previous findings that intolerance of uncertainty preceded
      changes in worry over the course of treatment, intolerance of uncertainty scores
      predicted subsequent scores on all symptom measures in the experimental group. In
      contrast, worry and depression scores predicted subsequent intolerance of
      uncertainty scores in the control group.

PMID- 17548544
TI  - Improving quality of life with epilepsy surgery: the seizure outcome is the key
      to success.

PMID- 17548545
TI  - New evidence for a genetic link between epilepsy and migraine.

PMID- 17548546
TI  - Disparities in the management of multiple sclerosis-related bladder symptoms.
AB  - BACKGROUND: Participants enrolled in the North American Research Committee on
      Multiple Sclerosis (NARCOMS) registry report disability status using Performance
      Scales (PS), a self-report measure. The bladder/bowel subscale (PSB) of PS has
      not been validated. It is also unknown whether ethnic or socioeconomic
      disparities exist in bladder care. OBJECTIVE: We aimed to validate the
      bladder/bowel subscale used by the NARCOMS registry and to describe urologic
      symptoms, investigations, and treatments received by registry participants.
      METHODS: In the Fall 2005 update questionnaire, we collected the Bowel Control
      Scale (BWCS) and Urogenital Distress Inventory-6 (UDI-6) as criterion measures
      and urologic investigations and treatments. We measured associations between
      investigations, treatments, and symptoms with clinical and sociodemographic
      variables using chi(2) tests for categorical variables and Kruskal-Wallis tests
      for continuous variables, followed by multivariable logistic regression. RESULTS:
      Nine thousand six hundred eighty-eight participants completed the survey. For the
      UDI-6, the median (interquartile range) score was 33.3 (16.7 to 50.0), for the
      BWCS 3 (1 to 6), and for the PSB 1 (1 to 3). The correlation between the PSB and
      the UDI-6 was r = 0.67 and between the PSB and the BWCS r = 0.53 (both p <
      0.0001). Participants had increased odds of receiving medication for bladder
      symptoms if they had health insurance (odds ratio [OR] 1.90; 1.07 to 3.35).
      Participants who were white (OR 1.5; 1.16 to 1.94) and had health insurance (OR
      2.0; 1.3 to 3.07) had increased odds of undergoing urologic investigations.
      CONCLUSION: The Performance Scales bladder question has adequate criterion and
      construct validity in multiple sclerosis (MS). There are ethnic and socioeconomic
      disparities in bladder management in MS.

PMID- 17548547
TI  - Neuroimaging of neuronal circuits involved in tic generation in patients with
      Tourette syndrome.
AB  - OBJECTIVE: To identify brain regions generating tics in patients with Tourette
      syndrome using sleep as a baseline. METHODS: We used [15O]H2O PET to study nine
      patients with Tourette syndrome and nine matched control subjects. For patients,
      conditions included tic release states and sleep stage 2; and for control
      subjects, rest states and sleep stage 2. RESULTS: Our study showed robust
      activation of cerebellum, insula, thalamus, and putamen during tic release.
      CONCLUSION: The network of structures involved in tics includes the activated
      regions and motor cortex. The prominent involvement of cerebellum and insula
      suggest their involvement in tic initiation and execution.

PMID- 17548548
TI  - Worsening of quality of life after epilepsy surgery: effect of seizures and
      memory decline.
AB  - BACKGROUND: Surgery for intractable temporal lobe epilepsy usually controls
      seizures and improves health-related quality of life (HRQOL), but some patients
      experience continued seizures, memory decline, or both. The relative impact of
      these unfavorable outcomes on HRQOL has not been described. METHODS: We studied
      seizure control, memory change, and HRQOL among 138 patients in the Multicenter
      Study of Epilepsy Surgery (MSES), an ongoing, prospective study of epilepsy
      surgery outcomes. Seizure remission at 2 years and 5 years was prospectively
      determined based upon regularly scheduled follow-up calls to study patients
      throughout the follow-up period. HRQOL was assessed annually using the Quality of
      Life in Epilepsy Inventory (QOLIE-89). Memory decline was determined by change in
      verbal delayed recall from baseline to the 2- or 5-year follow-up. RESULTS: HRQOL
      improved in patients who were in remission at the 2-year or 5-year follow-up,
      regardless of memory outcome. Among those not in remission at both 2 and 5 years
      (25/138, 18%), HRQOL remained stable when memory did not decline (14/138, 10%),
      but HRQOL declined when memory did decline (11/138, 8%). These 11 patients had
      baseline characteristics predictive of poor seizure or memory outcome. Declines
      were most apparent on HRQOL subscales assessing memory, role limitations, and
      limitations in work, driving, and social activities. CONCLUSIONS: After temporal
      resection, health-related quality of life (HRQOL) improves or remains stable in
      seizure-free patients despite memory decline, but HRQOL declines when persistent
      seizures are accompanied by memory decline. These results may be useful in
      presurgical counseling and identifying patients at risk for poor psychosocial
      outcome following surgery.

PMID- 17548549
TI  - A randomized controlled trial of resistance exercise in individuals with ALS.
AB  - OBJECTIVE: To determine the effects of resistance exercise on function, fatigue,
      and quality of life in individuals with ALS. METHODS: Subjects with a diagnosis
      of clinically definite, probable, or laboratory-supported ALS, forced vital
      capacity (FVC) of 90% predicted or greater, and an ALS Functional Rating Scale
      (ALSFRS) score of 30 or greater were randomly assigned to a resistance exercise
      group that received a home exercise program consisting of daily stretching and
      resistance exercises three times weekly or to a usual care group, who performed
      only the daily stretching exercises. ALSFRS, the Fatigue Severity Scale (FSS),
      and Short Form-36 (SF-36) were completed at baseline and monthly for 6 months.
      FVC and maximum voluntary isometric contraction (MVIC) were monitored monthly
      throughout the study. RESULTS: Of 33 subjects screened, 27 were randomly assigned
      (resistance = 13; usual care = 14). Eight resistance exercise subjects and 10
      usual care subjects completed the trial. At 6 months, the resistance exercise
      group had significantly higher ALSFRS and SF-36 physical function subscale
      scores. No adverse events related to the intervention occurred, MVIC and FVC
      indicated no negative effects, and less decline in leg strength measured by MVIC
      was found in the resistance exercise group. CONCLUSION: Our study, although
      small, showed that the resistance exercise group had significantly better
      function, as measured by total ALS Functional Rating Scale and upper and lower
      extremity subscale scores, and quality of life without adverse effects as
      compared with subjects receiving usual care.

PMID- 17548550
TI  - A pilot randomized education rehabilitation trial is feasible in sickle cell and
      strokes.
AB  - A randomized trial was completed to assess the feasibility of a 2-year education
      rehabilitation program for students with sickle cell disease and memory deficits.
      Eleven students were assigned to tutoring with or without memory training for 2
      years. Eighty-two percent completed the program. Evidence of improvement in
      memory and academic achievement existed. Educational rehabilitation is a feasible
      strategy, but further investigation is needed to assess the benefit in a multi
      center trial.

PMID- 17548551
TI  - Do alpha-synuclein aggregates in autonomic plexuses predate Lewy body disorders?:
      a cohort study.
AB  - OBJECTIVE: To determine the prevalence of alpha-synuclein (AS) aggregates in
      abdominopelvic autonomic plexuses in the general population and to evaluate the
      relationship between this finding and the subsequent development of neurologic
      dysfunction. METHODS: First, surgical specimens from 100 patients (ages 44 to 84)
      undergoing a wide resection of an abdominopelvic organ were examined by anti-AS
      immunostaining. Second, 16 patients (6 AS+ and 10 randomly selected AS-)
      participated in yearly double-blinded neurologic assessments. RESULTS: AS
      aggregates were found in autonomic plexuses in 9% of the whole sample (95% CI 3.4
      to 14.6%) but were more common in vesicoprostatic (26%) than in digestive tract
      (4%) specimens. At 16 months after the biopsy, no prevalent cases of Parkinson
      disease, dementia, or autonomic failure were diagnosed among participants. One
      AS+ patient had previously been diagnosed with REM sleep behavior disorder. Seven
      of 10 control subjects but none of the 6 AS+ patients had a diagnosis of
      hypertension (p = 0.01). During phase IV of Valsalva maneuver, AS+ group
      exhibited a longer blood pressure recovery time (p = 0.03), with one patient
      showing absence of blood pressure overshoot. Cardiac
      [(123)I]metaiodobenzylguanidine uptake was reduced in the AS+ group (p = 0.03).
      Striatal [(123)I]ioflupane uptake was abnormally low in only one AS+ patient. At
      30 months after the biopsy, lower cardiac and striatal uptake values tended to
      correlate with higher Unified Parkinson's Disease Rating Scale III scores (p =
      0.07). CONCLUSION: The common presence of alpha-synuclein aggregates in
      peripheral autonomic neurons may represent an early presymptomatic phase in the
      development of Lewy body disorders.

PMID- 17548552
TI  - An epidemiologic study of mild cognitive impairment in Kolkata, India.
AB  - OBJECTIVES: To estimate the prevalence of two types of mild cognitive impairment
      (MCI)-amnestic and multiple domain types-among nondemented and nondepressed
      elderly subjects aged 50 and older. METHODS: The study was carried out in
      Kolkata, the eastern metropolis of India. A cross-sectional community screening
      was carried out, and 960 subjects were selected by systematic random sampling for
      the assessment of cognitive function with the help of a validated cognitive
      questionnaire battery administered through house-to-house survey. A case-control
      study was also undertaken to identify potential risk factors through univariate
      analysis. RESULTS: Ultimately, full evaluation of cognitive function was possible
      in 745 of 960 subjects. An overall prevalence of MCI detected based on
      neuropsychological testing was 14.89% (95% CI: 12.19 to 17.95). Prevalence of the
      amnestic type was 6.04% (95% CI: 4.40 to 8.1) and that of the multiple domain
      type was 8.85% (95% CI: 6.81 to 11.32). Adjusted for age, education. and gender,
      the amnestic type was more common among men and the multiple domain type among
      women with advancement of age. Rates differed considerably with educational
      attainment. Hypertension and diabetes mellitus were the major risk factors for
      both types of MCI. CONCLUSION: In this first community-based study of mild
      cognitive impairment (MCI) from India, prevalence of the amnestic type is
      comparable with and that of the multiple domain type is less than the prevalence
      in developed countries. Variations in age, education, and gender specific
      prevalence of MCI of both types were encountered. The putative risk factors
      identified merit further study.

PMID- 17548553
TI  - Cognitive processing of visual stimuli in patients with organophosphate
      insecticide poisoning.
AB  - OBJECTIVE: To determine the effect of organophosphate (OP) insecticide poisoning
      on cognitive processing time of visual stimuli. METHODS: We compared 33 patients
      who recovered from the cholinergic phase (on average, 15 days after poisoning)
      with an age- and sex-matched control group. The tests used were simple visual
      reaction time (SVRT), recognition visual reaction time (RVRT), visual evoked
      potentials (VEP), and motor evoked potentials (MEP). The term cognitive
      processing time (CPT) was used to denote the time taken from the initial cortical
      perception of a stimulus to initiation of the descending motor impulse. CPT of
      each type of visual reaction was calculated by subtracting the sum of the visual
      impulse duration and the motor impulse duration from reaction time (CPT =
      reaction time-[P100 latency + total motor conduction time]). RESULTS: Both the
      SVRT and RVRT were significantly prolonged in patients. There was no significant
      difference in P100 latency or total motor conduction time (TMCT) between patients
      and the controls. However, CPT of simple visual reactions (CPT(SVR)) and the CPT
      of recognition visual reactions (CPT(RVR)) were significantly prolonged in
      patients. CONCLUSIONS: Acute organophosphate poisoning may slow higher-order
      cognitive processing involved in visual stimulus detection and visual stimulus
      discrimination, even after clinical recovery from the cholinergic phase.

PMID- 17548554
TI  - A door-to-door survey of intracranial atherosclerosis in Liangbei County, China.
AB  - We studied 590 asymptomatic villagers aged > or =40 years in Liangbei County in
      central rural China and found 41 subjects (prevalence 6.9%) with intracranial
      atherosclerosis. In a multivariate analysis, the significant risk factors for
      intracranial stenosis were hypertension (OR 2.53; 95% CI 1.12 to 5.72),
      glycosuria (OR 3; 1.19 to 7.97), heart disease (OR 4; 1.39 to 11.6), and family
      history of stroke (OR 5.2; 1.38 to 20). Intracranial atherosclerosis is not
      uncommon among asymptomatic Chinese subjects.

PMID- 17548555
TI  - Prevalence of asymptomatic intracranial atherosclerosis in high-risk patients.
AB  - We used transcranial Doppler to screen 3,057 patients who had at least one
      vascular risk factor of hypertension, diabetes, or hyperlipidemia and found 385
      (12.6%) had middle cerebral artery stenosis. Elderly, hypertension, diabetes, and
      hyperlipidemia were associated factors. The prevalence escalated quadratically
      with increasing number of associated factors: from 7.2% for one, to 29.6% for
      four associated factors. Asymptomatic middle cerebral artery stenosis is common
      in patients with vascular risk factors.

PMID- 17548556
TI  - Sirolimus-induced posterior reversible encephalopathy.

PMID- 17548557
TI  - New skeletal myopathy and cardiomyopathy associated with a missense mutation in
      MYH7.

PMID- 17548558
TI  - Silent T2* cerebral microbleeds: a potential new imaging clue in infective
      endocarditis.

PMID- 17548559
TI  - Is decreased dexterity in Parkinson disease due to apraxia?

PMID- 17548560
TI  - Pseudoseizure dogs.

PMID- 17548561
TI  - Increased incidence of deep venous thrombosis in ALS.

PMID- 17548562
TI  - CNS involvement in hereditary neuropathy with pressure palsies (HNPP).

PMID- 17548563
TI  - Pathogenesis of myelin/oligodendrocyte damage in multiple sclerosis.
AB  - Substantial evidence supports autoimmune activity as the etiologic mechanism
      underlying multiple sclerosis (MS). Both the innate and the adaptive arms of the
      immune system are involved in the aberrant response to several antigens
      associated with the myelin sheath and oligodendrocytes (OGCs) after the
      activation of immune cells by self- or cross-reactive microbial pathogens. The
      CD4(+) Th1 cell, in particular, has been implicated, but it is abetted by a
      variety of other cell types (CD8(+) cells, B cells, macrophages, and microglia)
      and soluble products (proteases, cytokines, and nitric oxide [NO]) that act both
      outside of and within the CNS. This review describes recent and salient findings
      from animal models and human clinical studies that have established our current
      understanding of the distinct steps in the development of immune autoreactivity
      that culminates in the CNS lesions associated with MS.

PMID- 17548564
TI  - Proceedings of a meeting to discuss neurodegeneration, neuroprotection and
      repair, and the interrelated issues of glial cells and myelin in multiple
      sclerosis. May 24, 2006. Geneva, Switzerland.

PMID- 17548565
TI  - Pathogenesis of axonal and neuronal damage in multiple sclerosis.
AB  - Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the
      CNS. Approximately 2 million people worldwide have MS, with females outnumbering
      males 2:1. Because of its high prevalence, MS is the leading cause of
      nontraumatic neurologic disability in young adults in the United States and
      Europe. Axon loss is the major cause of irreversible disability in patients with
      MS. Axon damage, including transection of the axon, begins early in MS and
      correlates with inflammatory activity. Several mechanisms lead to axon loss,
      including inflammatory secretions, loss of myelin-derived support, disruption of
      axonal ion concentrations, energy failure, and Ca(2+) accumulation. Therapeutic
      interventions directed toward each of these mechanisms need to be tested for
      their efficacy in enhancing axon survival and, ultimately, their ability to delay
      progression of neurologic disability in patients with MS.

PMID- 17548566
TI  - Experimental models of neuroprotection relevant to multiple sclerosis.
AB  - Activated T cells, particularly those of the T-helper (Th) 1 subset, have the
      capacity to kill neurons. Strategies for preventing such damage may include
      deviation of activated T cells into the Th2 subset (e.g., via use of glatiramer
      acetate), alteration of functional properties of Th1 cells (e.g., through use of
      interferon [INF]-beta or IV immunoglobulin), and inhibition of activated cell
      migration into the CNS (e.g., by employing INF-beta or natalizumab). Matrix
      metalloproteinase-9 (MMP-9) also causes neuron death in neurotoxicity models, and
      examination of medications with MMP inhibitory activity indicates that
      minocycline is capable of preventing such damage. Minocycline also has other
      properties relevant to conferring neuroprotection, such as inhibition of
      microglial activity and apoptosis pathways. In a small pilot study in patients
      with relapsing-remitting multiple sclerosis, minocycline treatment produced
      favorable outcomes in terms of gadolinium-enhancing lesions and clinical course.
      Further studies are needed to establish whether experimental neuroprotection
      strategies involving these mechanisms may be translated into preventing
      neurodegeneration in multiple sclerosis.

PMID- 17548567
TI  - Neuroprotection and repair by neurotrophic and gliotrophic factors in multiple
      sclerosis.
AB  - Based on the efficacy of immunomodulatory therapies in patients with multiple
      sclerosis (MS), much of the research and thinking about pathogenesis and
      treatment has traditionally focused on suppressing the immune system. Whatever
      the cause, recent studies have rekindled the notion that neurologic dysfunction
      in patients with MS relates best to the degree of neuronal (axonal) and glial
      damage. Therefore, as a means to understand the pathogenesis of MS and to develop
      biologically targeted new therapeutics, a greater understanding of axoglial
      biology is needed. Central to axoglial biology are protein regulatory factors
      that include gliotrophic factors such as the neuregulins and neurotrophic factors
      that communicate between these cell types and are critical for nervous system
      development. Unfortunately, the track record of neurotrophic factors for treating
      other neurologic disorders has not been impressive, in part because of a failure
      to aim these factors at appropriate pathophysiologic targets. Although future
      therapeutic strategies in MS may be able to take advantage of these factors, such
      strategies will require an in-depth understanding of how these factors signal and
      how they are naturally targeted to axons and glia in both health and disease.

PMID- 17548569
TI  - Neurodegeneration in multiple sclerosis: defining the problem.
AB  - It is increasingly apparent that neurodegeneration in multiple sclerosis (MS)
      begins earlier in the course of the disease than was previously believed. The
      loss of axons, which results in permanent deficits, is distributed beyond regions
      of abnormal-appearing CNS white matter, and a constant background of neuron loss
      continues to take place while clinical symptoms wax and wane. It is therefore
      important to precisely define the scope of neurodegeneration so that experimental
      and clinical approaches to providing neuroprotective therapies can be devised
      that will halt and reverse neuron damage. Some of the complexities involved in
      cellular interactions in the normal-appearing and obviously affected CNS are
      reviewed here as a starting point for the consideration of approaches to
      neuroprotective strategies.

PMID- 17548571
TI  - Dual role of inflammation in CNS disease.
AB  - Inflammatory responses in the CNS have usually been perceived to cause or
      contribute to neuron injury. However, emerging evidence suggests that
      inflammatory reactions can also be neuroprotective. The nervous and immune
      systems employ overlapping mechanisms and shared mediators that promote cross
      talk between the two systems. Immune cells, for example, produce not only
      neurodestructive molecules but also factors that can support neuroaxonal growth,
      survival, and plasticity. This might explain why inflammatory reactions may
      contribute to both injury and protection of neurons. The dual role of CNS
      inflammation also has important therapeutic implications that are only beginning
      to be explored.

PMID- 17548572
TI  - Can clinical outcomes be used to detect neuroprotection in multiple sclerosis?
AB  - Neuroprotection is a difficult concept to define in the context of multiple
      sclerosis (MS), a complex heterogeneous disease with an uncertain
      immunopathogenetic mechanism. Although treatment and natural history studies use
      clinical determinants and MRI metrics to assess disability, long-term
      progression, and the effects of disease-modifying drugs, the association between
      clinical and imaging outcomes is relatively modest. In the future, a composite
      measure comprising both clinical and imaging markers, along with investigational
      surrogates derived from molecular genetics and proteomics, may provide an
      accurate quantitative measure of neuroprotection. However, a consensus definition
      of "neuroprotection" applicable to MS needs to be established before such a tool
      can be validated and put to use.

PMID- 17548573
TI  - Can imaging techniques measure neuroprotection and remyelination in multiple
      sclerosis?
AB  - MRI is the most important paraclinical measure for assessing and monitoring the
      pathologic changes implicated in the onset and progression of multiple sclerosis
      (MS). Conventional MRI sequences, such as T1-weighted gadolinium-enhanced and
      spin-echo T2-weighted imaging, are unable to provide full details about the
      degree of inflammation and underlying neurodegenerative changes. Newer
      nonconventional MRI techniques have the potential to detect clinical impairment,
      disease progression, accumulation of disability, and the neuroprotective effects
      of treatment. Unenhanced T1-weighted imaging can reveal hypointense black holes,
      a measure of chronic neurodegeneration. Two- and three-dimensional fluid
      attenuated inversion recovery sequences allow better identification of cortical
      lesions. Ultrahigh-field strength MRI has the potential to detect subpial
      cortical and deep gray matter lesions. Magnetization transfer imaging is
      increasingly used to characterize the evolution of MS lesions and normal
      appearing brain tissue. Evidence suggests that the dynamics of magnetization
      transfer changes correlate with the extent of demyelination and remyelination.
      Magnetic resonance spectroscopy, which provides details on tissue biochemistry,
      metabolism, and function, also has the capacity to reveal neuroprotective
      mechanisms. By measuring the motion of water, diffusion imaging can provide
      information about the orientation, size, and geometry of tissue damage in white
      and gray matter. Functional MRI may help clarify the brain's plasticity-dependent
      compensatory mechanisms in patients with MS. High-resolution microautoradiography
      and new contrast agents are proving to be sensitive means for characterizing
      molecular markers of disease activity, such as activated microglia and
      macrophages. Optical coherence tomography, a new research technique, makes it
      possible to investigate relevant physiologic systems that provide accurate
      measures of tissue changes secondary to the MS disease process. Although
      detecting the status of neuronal integrity using MRI techniques continues to
      improve, a "gold standard" model remains to be established.

PMID- 17548574
TI  - Evidence for neuroprotection and remyelination using imaging techniques.
AB  - MRI is used routinely in clinical practice and pharmaceutical trials to measure
      disease activity and assess the effects of treatment in multiple sclerosis.
      Conventional MRI techniques sensitively detect inflammation, demyelination, and
      tissue injury. Less conventional imaging modalities, such as magnetic resonance
      spectroscopy and magnetization transfer imaging, and advanced image processing to
      quantify structural changes can provide more specific and inherently quantitative
      markers of the pathologic processes underlying the accumulation of disease burden
      and the progression of clinical disability. Together, these techniques can assess
      both the anti-inflammatory and the neuroprotective effects of immunomodulatory
      therapies.

PMID- 17548576
TI  - Response to B-cell depleting therapy with rituximab reverts the abnormalities of
      T-cell subsets in patients with idiopathic thrombocytopenic purpura.
AB  - Rituximab, an anti-CD20 monoclonal antibody, has been used to treat autoimmune
      disorders such as idiopathic thrombocytopenic purpura (ITP). However, its
      mechanisms of action as well as the effects on cellular immunity remain poorly
      defined. We investigated the changes of different peripheral blood T-cell
      subsets, the apoptosis profile, as well as the changes of T-cell receptor (TCR)
      beta-variable (VB) region gene usage of CD4+ and CD8+ T-cell subpopulations
      following rituximab therapy. The study involved 30 patients with chronic ITP who
      received rituximab, of whom 14 achieved a durable (> 6 months) response. Compared
      with the control group, pretreatment abnormalities of T cells in ITP patients
      included an increase of the Th1/Th2 ratio and of the Tc1/Tc2 ratios (P < .001),
      increased expression of Fas ligand on Th1 and Th2 cells (P < .001), increased
      expression of Bcl-2 mRNA (P = .003) and decreased expression of bax mRNA (P =
      .025) in Th cells, and expansion of oligoclonal T cells with no preferential use
      of any TCR VB subfamily. These abnormalities were reverted in responders at 3 and
      6 months after treatment, whereas they remained unchanged in nonresponders. Our
      findings indicate that in patients with ITP, response to B-cell depletion induced
      by rituximab is associated with significant changes of the T-cell compartment.

PMID- 17548577
TI  - The oxidase activity of vascular adhesion protein-1 (VAP-1) induces endothelial E
      and P-selectins and leukocyte binding.
AB  - Leukocyte migration from the blood into tissues is pivotal in immune homeostasis
      and in inflammation. During the multistep extravasation cascade, endothelial
      selectins (P- and E-selectin) and vascular adhesion protein-1 (VAP-1), a cell
      surface-expressed oxidase, are important in tethering and rolling. Here, we
      studied the signaling functions of the catalytic activity of VAP-1. Using human
      endothelial cells transfected with wild-type VAP-1 and an enzymatically inactive
      VAP-1 point mutant, we show that transcription and translation of E- and P
      selectins are induced through the enzymatic activity of VAP-1. Moreover, use of
      VAP-1-deficient animals and VAP-1-deficient animals carrying the human VAP-1 as a
      transgene show a VAP-enzyme activity-dependent induction of P-selectin in vivo.
      Up-regulation of P-selectin was found both in high endothelial venules in
      lymphoid tissues and in flat-walled vessels in noninflamed tissues. VAP-1
      activity in vivo led to increased P-selectin-dependent binding of lymphocytes to
      endothelial cells. These data show that the oxidase reaction catalyzed by VAP-1
      alters the expression of other molecules involved in the leukocyte extravasation
      cascade. Our findings indicate cross-talk between adhesion molecules involved in
      the tethering and rolling of leukocytes and show that VAP-1-dependent signaling
      can prime the vessels for an enhanced inflammatory response.

PMID- 17548578
TI  - EPO modulation of cell-cycle regulatory genes, and cell division, in primary bone
      marrow erythroblasts.
AB  - Erythropoietin (EPO's) actions on erythroblasts are ascribed largely to survival
      effects. Certain studies, however, point to EPO-regulated proliferation. To
      investigate this problem in a primary system, Kit(pos)CD71(high) erythroblasts
      were prepared from murine bone marrow, and were first used in the array-based
      discovery of EPO-modulated cell-cycle regulators. Five cell-cycle progression
      factors were rapidly up-modulated: nuclear protein 1 (Nupr1), G1 to S phase
      transition 1 (Gspt1), early growth response 1 (Egr1), Ngfi-A binding protein 2
      (Nab2), and cyclin D2. In contrast, inhibitory cyclin G2, p27/Cdkn1b, and B-cell
      leukemia/lymphoma 6 (Bcl6) were sharply down-modulated. For CYCLIN G2, ectopic
      expression also proved to selectively attenuate EPO-dependent UT7epo cell-cycle
      progression at S-phase. As analyzed in primary erythroblasts expressing minimal
      EPO receptor alleles, EPO repression of cyclin G2 and Bcl6, and induction of
      cyclin D2, were determined to depend on PY343 (and Stat5) signals. Furthermore,
      erythroblasts expressing a on PY-null EPOR-HM allele were abnormally distributed
      in G0/G1. During differentiation divisions, EPOR-HM Ter119(pos) erythroblasts
      conversely accumulated in S-phase and faltered in an apparent EPO-directed
      transition to G0/G1. EPO/EPOR signals therefore control the expression of select
      cell-cycle regulatory genes that are proposed to modulate stage-specific
      decisions for erythroblast cell-cycle progression.

PMID- 17548580
TI  - Conversion of platelets from a proaggregatory to a proinflammatory adhesive
      phenotype: role of PAF in spatially regulating neutrophil adhesion and spreading.
AB  - The ability of platelets to provide a highly reactive surface for the recruitment
      of other platelets and leukocytes to sites of vascular injury is critical for
      hemostasis, atherothrombosis, and a variety of inflammatory diseases. The
      mechanisms coordinating platelet-platelet and platelet-leukocyte interactions
      have been well defined and, in general, it is assumed that increased platelet
      activation correlates with enhanced reactivity toward other platelets and
      neutrophils. In the current study, we demonstrate a differential role for
      platelets in supporting platelet and neutrophil adhesive interactions under flow.
      We demonstrate that the conversion of spread platelets to microvesiculated
      procoagulant (annexin A5-positive [annexin A5+ve]) forms reduces platelet
      platelet adhesion and leads to a paradoxical increase in neutrophil-platelet
      interaction. This enhancement in neutrophil adhesion and spreading is partially
      mediated by the proinflammatory lipid, platelet-activating factor (PAF). PAF
      production, unlike other neutrophil chemokines (IL-8, GRO-alpha, NAP-2, IL-1beta)
      is specifically and markedly up-regulated in annexin A5+ve cells.
      Physiologically, this spatially controlled production of PAF plays an important
      role in localizing neutrophils on the surface of thrombi. These studies define
      for the first time a specific proinflammatory function for annexin A5+ve
      platelets. Moreover, they demonstrate an important role for platelet-derived PAF
      in spatially regulating neutrophil adhesion under flow.

PMID- 17548579
TI  - A novel role for HMGB1 in TLR9-mediated inflammatory responses to CpG-DNA.
AB  - CpG-DNA or its synthetic analog CpG-ODN activates innate immunity through Toll
      like receptor 9 (TLR9). However, the mechanism of TLR9 activation by CpG-DNA
      remains elusive. Here we have identified HMGB1 as a CpG-ODN-binding protein.
      HMGB1 interacts and preassociates with TLR9 in the endoplasmic reticulum-Golgi
      intermediate compartment (ERGIC), and hastens TLR9's redistribution to early
      endosomes in response to CpG-ODN. CpG-ODN stimulates macrophages and dendritic
      cells to secrete HMGB1; in turn, extracellular HMGB1 accelerates the delivery of
      CpG-ODNs to its receptor, leading to a TLR9-dependent augmentation of IL-6, IL
      12, and TNFalpha secretion. Loss of HMGB1 leads to a defect in the IL-6, IL-12,
      TNFalpha, and iNOS response to CpG-ODN. However, lack of intracellular TLR9
      associated HMGB1 can be compensated by extracellular HMGB1. Thus, the DNA-binding
      protein HMGB1 shuttles in and out of immune cells and regulates inflammatory
      responses to CpG-DNA.

PMID- 17548581
TI  - Comment on "A novel pathway that regulates inflammatory disease in the
      respiratory tract".

PMID- 17548583
TI  - Cutting edge: Transitional T3 B cells do not give rise to mature B cells, have
      undergone selection, and are reduced in murine lupus.
AB  - As the immediate precursors to mature follicular B cells in splenic development,
      immature transitional cells are an essential component for understanding late B
      cell differentiation. It has been shown that T2 cells can give rise to mature B
      cells; however, whether T3 B cells represent a normal stage of B cell
      development, which has been widely assumed, has not been fully resolved. In this
      study, we demonstrate both in vitro and in vivo that T3 B cells do not give rise
      to mature B cells and are instead selected away from the T1-->T2-->mature B cell
      developmental pathway and are hyporesponsive to stimulation through the BCR.
      Significantly reduced numbers of T3 B cells in young lupus-prone mice further
      suggest that the specificity of this subset holds clues to understanding
      autoimmunity.

PMID- 17548582
TI  - The innate immune system in allograft rejection and tolerance.
AB  - As T cells alone are both necessary and sufficient for the rejection of virtually
      all allogeneic tissues, much of transplantation immunology has focused on cells
      of the adaptive immune system. During the past decade, advances in our
      understanding of innate responses to pathogen-associated molecules have spurred a
      "rediscovery" of innate immunity. Fueled by this, an increasing body of
      literature has emerged in which the role of the innate immune system in allograft
      rejection and tolerance has been examined more closely. This review will give an
      overview of recent studies and emerging concepts of how the cellular components
      of the innate immune system participate in the immune response to solid organ
      transplantation. These important studies highlight the complex interplay between
      diverse cells of the immune response and provide the basis for optimal strategies
      of tolerance induction.

PMID- 17548584
TI  - Cutting edge: Essential role of hypoxia inducible factor-1alpha in development of
      lipopolysaccharide-induced sepsis.
AB  - Sepsis, the leading cause of death in intensive care units, reflects a
      detrimental host response to infection in which bacteria or LPS act as potent
      activators of immune cells, including monocytes and macrophages. In this report,
      we show that LPS raises the level of the transcriptional regulator hypoxia
      inducible factor-1alpha (HIF-1alpha) in macrophages, increasing HIF-1alpha and
      decreasing prolyl hydroxylase mRNA production in a TLR4-dependent fashion. Using
      murine conditional gene targeting of HIF-1alpha in the myeloid lineage, we
      demonstrate that HIF-1alpha is a critical determinant of the sepsis phenotype.
      HIF-1alpha promotes the production of inflammatory cytokines, including TNF
      alpha, IL-1, IL-4, IL-6, and IL-12, that reach harmful levels in the host during
      early sepsis. HIF-1alpha deletion in macrophages is protective against LPS
      induced mortality and blocks the development of clinical markers including
      hypotension and hypothermia. Inhibition of HIF-1alpha activity may thus represent
      a novel therapeutic target for LPS-induced sepsis.

PMID- 17548585
TI  - Cutting edge: A common polymorphism impairs cell surface trafficking and
      functional responses of TLR1 but protects against leprosy.
AB  - TLRs constitute an essential family of pattern recognition molecules that,
      through direct recognition of conserved microbial components, initiate
      inflammatory responses following infection. In this role, TLR1 enables host
      responses to a variety of bacteria, including pathogenic species of mycobacteria.
      In this study, we report that I602S, a common single nucleotide polymorphism
      within TLR1, is associated with aberrant trafficking of the receptor to the cell
      surface and diminished responses of blood monocytes to bacterial agonists. When
      expressed in heterologous systems, the TLR1 602S variant, but not the TLR1 602I
      variant, exhibits the expected deficiencies in trafficking and responsiveness.
      Among white Europeans, the 602S allele represents the most common single
      nucleotide polymorphism affecting TLR function identified to date. Surprisingly,
      the 602S allele is associated with a decreased incidence of leprosy, suggesting
      that Mycobacterium leprae subverts the TLR system as a mechanism of immune
      evasion.

PMID- 17548586
TI  - Cutting edge: Human Th17 cells are identified as bearing CCR2+CCR5- phenotype.
AB  - Recent reports have shown that IL-17-producing CD4+ T cells (Th17 cells) belong
      to a distinct helper T cell lineage and are critically involved in the
      pathogenesis of autoimmune diseases and allergies. However, the chemokine
      receptor profile of Th17 cells remains to be clarified. In this study, we report
      that human Th17 cells are identified as CCR2+CCR5- memory CD4+ T cells. Analysis
      of PBMC from healthy donors showed that CCR2+ cells produce much larger amounts
      of IL-17 than CCR2- cells, indicating the preferential expression of CCR2 on Th17
      cells. Notably, CCR2+CCR5- memory CD4+ T cells produced a large amount of IL-17
      and little IFN-gamma, whereas CCR2+CCR5+ cells reciprocally produced an enormous
      amount of IFN-gamma but little IL-17. Moreover, a higher expression of T-bet was
      seen in the CCR5+ memory T cells. These results indicate that absence of CCR5
      distinguishes human Th17 cells from Th1 cells.

PMID- 17548587
TI  - TLR stimulation modifies BLyS receptor expression in follicular and marginal zone
      B cells.
AB  - Through their differential interactions with B lymphocyte stimulator (BLyS) and a
      proliferation-inducing ligand (APRIL), the three BLyS family receptors play
      central roles in B cell survival and differentiation. Recent evidence indicates
      BLyS receptor levels shift following BCR ligation, suggesting that activation
      cues can alter overall BLyS receptor profiles and thus ligand sensitivity. In
      this study, we show that TLR stimuli also alter BLyS receptor expression, but in
      contrast to BCR ligation, TLR9 and TLR4 signals, preferentially increase
      transmembrane activator calcium modulator and cyclophilin ligand interactor
      (TACI) expression. Although both of these TLRs act through MyD88-dependent
      mechanisms to increase TACI expression, they differ in terms of their downstream
      mediators and the B cell subset affected. Surprisingly, only TLR4 relies on c-Rel
      and p50 to augment TACI expression, whereas TLR9 does not. Furthermore, although
      all follicular and marginal zone B cells up-regulate TACI in response to TLR9
      stimulation, only marginal zone B cells and a subset of follicular B cells
      respond to TLR4. Finally, we find that both BLyS and APRIL enhance viability
      among quiescent and BCR-stimulated B cells. However, although BLyS enhances
      viability among TLR stimulated B cells, APRIL does not, suggesting that TACI but
      not BLyS receptor 3 may share survival promoting pathways with TLRs.

PMID- 17548588
TI  - Type I IFN contributes to NK cell homeostasis, activation, and antitumor
      function.
AB  - This study demonstrates that type I IFNs are an early and critical regulator of
      NK cell numbers, activation, and antitumor activity. Using both IFNAR1- and
      IFNAR2-deficient mice, as well as an IFNAR1-blocking Ab, we demonstrate that
      endogenous type I IFN is critical for controlling NK cell-mediated antitumor
      responses in many experimental tumor models, including protection from
      methylcholanthrene-induced sarcomas, resistance to the NK cell-sensitive RMA-S
      tumor and cytokine immunotherapy of lung metastases. Protection from RMA-S
      afforded by endogenous type I IFN is more potent than that of other effector
      molecules such as IFN-gamma, IL-12, IL-18, and perforin. Furthermore, cytokine
      immunotherapy using IL-12, IL-18, or IL-21 was effective in the absence of
      endogenous type I IFN, however the antimetastatic activity of IL-2 was abrogated
      in IFNAR-deficient mice, primarily due to a defect in IL-2-induced cytotoxic
      activity. This study demonstrates that endogenous type I IFN is a central
      mediator of NK cell antitumor responses.

PMID- 17548589
TI  - Agonist-driven development of CD4+CD25+Foxp3+ regulatory T cells requires a
      second signal mediated by Stat6.
AB  - The factors that induce Foxp3 expression and regulatory T (Treg) cell development
      remain unknown. In this study, we investigated the role of STAT4 and STAT6 in
      agonist-driven generation of Ag-specific Foxp3-expressing Treg cells. Our
      findings indicate that fully efficient induction of Foxp3 expression and
      development of Ag-specific Treg cells requires the synergistic action of two
      signals: a TCR-mediated signal and a second signal mediated by STAT6. Indeed, by
      comparing the development of wild-type and STAT4- and STAT6-deficient
      hemagglutinin-specific T cells in the presence of hemagglutinin Ag, we found that
      the absence of STAT6 impaired the generation of Ag-specific CD4+CD25+Foxp3+
      cells. Moreover, in transgenic mice expressing a constitutively active form of
      STAT6, we found that the fraction of CD4+Foxp3+ cells exceeds that of control
      wild-type littermates. Overall these findings support a role for the STAT6
      pathway in Treg cell development and maintenance.

PMID- 17548590
TI  - Rates of processing determine the immunogenicity of immunoproteasome-generated
      epitopes.
AB  - CD8 T cells resolve intracellular pathogens by responding to pathogen-derived
      peptides that are presented on the cell surface by MHC class I molecules.
      Although most pathogens encode a large variety of antigenic peptides, protective
      CD8 T cell responses target usually only a few of these. To determine the
      mechanism by which the IFN-gamma-inducible proteasome (immuno) subunits enhance
      the ability of specific pathogen-derived peptides to elicit CD8 T cell responses,
      we generated a recombinant Listeria monocytogenes strain (rLM-E1) that secretes a
      model Ag encompassing the immunoproteasome-dependent E1B(192-200) and
      immunoproteasome-independent E1A(234-243) epitope. Analyses of Ag presentation
      showed that infected gene-deficient professional APCs, lacking the immunosubunits
      LMP7/ibeta5 and MECL-1/ibeta2, processed and presented the rLM-E1-derived E1B(192
      200) epitope but with delayed kinetics. E1A epitope processing proceeded normally
      in these cells. Accordingly, infected gene-deficient mice failed to respond to
      the otherwise immunodominant E1B(192-200) epitope but mounted normal CD8 T cell
      responses to E1A(234-243) which was processed by the same professional APCs, from
      the same rLM-E1 Ag. The inability of gene-deficient mice to respond to E1B(192
      200) was not explained by insufficient quantities of antigenic peptide, as
      splenic APC of 36-h-infected gene-deficient mice that presented the two E1
      epitopes at steady state levels elicited responses to both E1B(192-200) and
      E1A(234-243) when transferred into LMP7+MECL-1-deficient mice. Taken together,
      our findings indicate that not absolute epitope quantities but early Ag
      processing kinetics determine the ability of pathogen-derived peptides to elicit
      CD8 T cell responses, which is of importance for rational T cell vaccine design.

PMID- 17548591
TI  - Persistent depots of influenza antigen fail to induce a cytotoxic CD8 T cell
      response.
AB  - Encounter with Ag during chronic infections results in the generation of
      phenotypically and functionally heterogeneous subsets of Ag-specific CD8 T cells.
      Influenza, an acute infection, results in the generation of similar CD8 T cell
      heterogeneity, which may be attributed to long-lived depots of flu Ags that
      stimulate T cell proliferation well after virus clearance. We hypothesized that
      the heterogeneity of flu-specific CD8 T cells and maintenance of T cell memory
      required the recruitment of new CD8 T cells to persistent depots of flu Ag, as
      was the case for flu-specific CD4 T cell responses. However, robust expansion and
      generation of highly differentiated cytolytic effectors and memory T cells only
      occurred when naive CD8 T cells were primed during the first week of flu
      infection. Priming of new naive CD8 T cells after the first week of infection
      resulted in low numbers of poorly functional effectors, with little to no
      cytolytic activity, and a negligible contribution to the memory pool. Therefore,
      although the presentation of flu Ag during the late stages of infection may
      provide a mechanism for maintaining an activated population of CD8 T cells in the
      lung, few latecomer CD8 T cells are recruited into the functional memory T cell
      pool.

PMID- 17548592
TI  - Systemic administration of IL-23 induces potent antitumor immunity primarily
      mediated through Th1-type response in association with the endogenously expressed
      IL-12.
AB  - IL-23, a cytokine, which is composed of the p40 subunit shared with IL-12 and the
      IL-23-specific p19 subunit, has been shown to preferentially act on Th1
      effector/memory CD4+ T cells and to induce their proliferation and IFN-gamma
      production. The IL-23 is also reported to act on Th17-CD4+ T cells, which are
      involved in inducing tissue injury. In this study, we examined the antitumor
      effects associated with systemic administration of IL-23 and their mechanisms in
      mouse tumor system. Systemic administration of high-dose IL-23 was achieved using
      in vivo electroporation of IL-23 plasmid DNA into the pretibial muscles of
      C57BL/6 mice. The IL-23 treatment was associated with significant suppression of
      the growth of pre-existing MCA205 fibrosarcoma and prolongation of the survival
      of treated mice without significant toxicity when compared with those of the mice
      treated with EGFP. Although the therapeutic outcomes were similar to those with
      the IL-12 treatment, the IL-23 treatment induced characteristic immune responses
      distinctive to those of IL-12 treatment. The IL-23 administration even at the
      therapeutic levels did not induce detectable IFN-gamma concentration in the
      serum. In vivo depletion of CD4+ T cells, CD8+ T cells, or NK cells significantly
      inhibited the antitumor effects of IL-23. Furthermore, the CD4+ T cells in the
      lymph nodes in the IL-23-treated mice showed significant IFN-gamma and IL-17
      response upon anti-CD3 mAb stimulation in vitro. These results and the ones in
      the IFN-gamma or IL-12 gene knockout mice suggest that potent antitumor effects
      of IL-23 treatment could be achieved when the Th1-type response is fully promoted
      in the presence of endogenously expressed IL-12.

PMID- 17548593
TI  - A novel role of complement factor C1q in augmenting the presentation of antigen
      captured in immune complexes to CD8+ T lymphocytes.
AB  - Ag-IgG immune complexes (IC) are efficiently taken up, and Ag-derived peptides
      are subsequently processed and presented by APC. In vitro experiments indicate
      that IgG Fc Receptors (FcgammaR) facilitate the efficient uptake of IC by
      dendritic cells. Previous experiments showed that the cross-presentation of Ag
      derived peptides after s.c. administration of IC is FcgammaR-dependent. To study
      the role of different FcgammaR and complement in MHC class I Ag presentation
      after i.v. administration, we used mice deficient for FcgammaRs and complement
      components. These mice were injected with CFSE-labeled OVA-specific CD8+ T cells
      followed by administration of IC composed of OVA and rabbit anti-OVA IgG i.v. to
      measure MHC class I presentation of OVA-derived peptides. The Ag presentation was
      partly reduced in FcRgamma-chain-deficient mice, but not affected in
      FcgammaRI/II/III-deficient mice, complement factor C3-deficient mice, or
      FcgammaRI/II/III x C3-deficient mice. Importantly, CD8+ T cell proliferation was
      significantly reduced in mice deficient for C1q. This proliferation could be
      restored when IC were incubated with purified human C1q before injection.
      Likewise, purified C1q could strongly enhance the uptake and presentation of IC
      by dendritic cells in vitro. Heat inactivation abrogated the C1q-mediated uptake
      of IC. In addition, in vivo uptake of OVA-IC in the spleen was significantly
      reduced in C1q-deficient mice compared with wild-type mice. Together, these
      results indicate a novel function of C1q, which is present in high levels in the
      bloodstream, by directly enhancing the uptake and MHC class I presentation of Ag
      captured in IC by APC to CD8+ T cells.

PMID- 17548594
TI  - Uptake of human papillomavirus virus-like particles by dendritic cells is
      mediated by Fcgamma receptors and contributes to acquisition of T cell immunity.
AB  - Chimeric human papillomavirus virus-like particles (HPV cVLP) are immunogens able
      to elicit potent CTL responses in mice against HPV16-transformed tumors; however,
      the mechanism of T cell priming has remained elusive. HPV VLP bind to human MHC
      class II-positive APCs through interaction with FcgammaRIII, and immature
      dendritic cells (DC) become activated after incubation with HPV VLP; however, it
      is unclear whether FcgammaR on DC are involved. In mice, FcgammaRII and
      FcgammaRIII are homologous and bind similar ligands. In this study, we show that
      binding and uptake of VLP by DC from FcgammaRII, FcgammaRIII, and FcgammaRII/III
      deficient mice are reduced by up to 50% compared with wild-type mice.
      Additionally, maturation of murine DC from FcgammaRII/III-deficient mice by VLP
      is also reduced, indicating that DC maturation, and thus Ag presentation, is
      diminished in the absence of expression of FcgammaR. To investigate the in vivo
      contribution of FcgammaR in the induction of cellular immunity, FcgammaR single-
      and double-knockout mice were immunized with HPV16 L1/L2-E7 cVLP, and the
      frequency of E7-specific T cells was analyzed by tetramer binding, IFN-gamma
      ELISPOT, and cytotoxicity assays. All readouts indicated that the frequency of E7
      specific CD4(+) and CD8(+) T cells induced in all FcgammaR-deficient mice after
      immunization with cVLP was significantly diminished. Based on these results, we
      propose that the low-affinity FcgammaR contribute to the high immunogenicity of
      HPV VLP during T cell priming by targeting VLP to DC and inducing a maturation
      state of the DC that facilitates Ag presentation to and activation of naive T
      cells.

PMID- 17548595
TI  - Impaired accumulation of antigen-specific CD8 lymphocytes in chemokine CCL25
      deficient intestinal epithelium and lamina propria.
AB  - CCL25 and CCR9 constitute a chemokine/receptor pair involved in T cell
      development and in gut-associated immune responses. In this study, we generated
      CCL25(-/-) mice to answer questions that could not be addressed with existing
      CCR9(-/-) mice. Similar phenotypes were observed for both CCL25(-/-) and CCR9(-/
      ) mice, consistent with the notion that CCL25 and CCR9 interact with each other
      exclusively. We assessed the requirement for CCL25 in generating CCR9(high) CD8
      intestinal memory-phenotype T cells and the subsequent accumulation of these
      cells within effector sites. TCR-transgenic naive CD8 T cells were transferred
      into wild-type or CCL25-deficient hosts. Oral sensitization with Ag allowed these
      naive donor cells to efficiently differentiate into CCR9(high) memory-phenotype
      cells within the mesenteric lymph nodes of wild-type hosts. This differentiation
      event occurred with equal efficiency in the MLN of CCL25-deficient hosts,
      demonstrating that CCL25 is not required to induce the CCR9(high) memory
      phenotype in vivo. However, we found that CCL25 deficiency severely impaired the
      Ag-dependent accumulation of donor-derived CD8 T cells within both lamina propria
      and epithelium of the small intestine. Thus, although CCL25 is not necessary for
      generating memory-phenotype CD8 T cells with "gut-homing" properties, this
      chemokine is indispensable for their trafficking to the small intestine.

PMID- 17548596
TI  - IL-27 synthesis induced by TLR ligation critically depends on IFN regulatory
      factor 3.
AB  - IL-27 is a heterodimeric cytokine composed of EBV-induced gene 3 and p28.
      Produced by dendritic cells (DCs) in response to TLR ligands, IL-27 recently
      emerged as a key regulator of inflammatory responses. In this study, we first
      demonstrate that Toll/IL-1R-containing adaptor inducing IFN-beta and its
      associated IFN regulatory factor (IRF) 3 transcription factor are critically
      involved in IL-27p28 expression in mouse DCs stimulated by TLR ligands. We then
      show that IL-27 serum levels are dramatically reduced in IRF3(-/-) upon LPS
      injection, indicating a critical role for IRF3 in TLR4-mediated IL-27 production
      in vivo. We identified an IRF3-binding site within the IL-27p28 promoter region
      which is required for IL-27p28 gene activation in reporter gene assays. In human
      DCs, IL-27p28 mRNA was preferentially induced by Toll/IL-1R-containing adaptor
      inducing IFN-beta-coupled TLR ligands and following CMV infection. Furthermore,
      chromatin immunoprecipitation studies demonstrate that IRF3 is recruited to the
      endogenous p28 promoter in TLR4-stimulated human DCs. We conclude that IRF3
      activation is a master switch for IL-27 synthesis.

PMID- 17548597
TI  - Disregulated influenza A virus-specific CD8+ T cell homeostasis in the absence of
      IFN-gamma signaling.
AB  - Recent studies indicate that IFN-gamma may influence both the expansion and the
      trafficking of virus-specific CD8+ CTL, though the effects are not necessarily
      consistent for different models of viral and bacterial disease. Influenza A virus
      infection of mice deficient for IFN-gamma (IFN-gamma(-/-)) or deficient for the
      IFN-gamma receptor 1 (IFNGR1(-/-)) was, when compared with the wild-type (WT) B6
      controls, associated with increased Ag-specific CD8+ T cell counts in the spleen
      and mediastinal lymph nodes. At the same time, fewer of these CTL effectors were
      found in the bronchoalveolar lavage population recovered from the IFN-gamma(-/-)
      mice. Comparable effects were observed for WT mice treated with a neutralizing
      IFN-gamma-specific mAb. Transfer of WT memory Thy1.1(+) CD8+ populations into
      Thy1.2+ B6 IFN-gamma(-/-) or IFNGR1(-/-) mice followed by intranasal virus
      challenge demonstrated both that IFN-gamma produced by the host was important for
      the regulation of Ag-specific CTL numbers and that IFN-gamma was likely to act
      directly on the T cells themselves. In addition, the prevalence of CTLs
      undergoing apoptosis in spleen was lower when measured directly ex vivo for IFN
      gamma(-/-) vs WT B6 mice. The present analysis is the first comprehensive
      demonstration that IFN-gamma signaling can differentially regulate both Ag
      specific CTL homeostasis in secondary lymphoid organs and trafficking to a site
      of virus-induced pathology.

PMID- 17548598
TI  - Immunomodulatory mediators from pollen enhance the migratory capacity of
      dendritic cells and license them for Th2 attraction.
AB  - The immune response of atopic individuals against allergens is characterized by
      increased levels of Th2 cytokines and chemokines. However, the way in which the
      cytokine/chemokine profile is matched to the type of invading allergen, and why
      these profiles sometimes derail and lead to disease, is not well understood. We
      recently demonstrated that pollen modulates dendritic cell (DC) function in a way
      that results in an enhanced capacity to initiate Th2 responses in vitro. Here, we
      examined the effects of aqueous birch pollen extracts (Bet.-APE) on chemokine
      receptor expression and chemokine production by human monocyte-derived DCs. Bet.
      APE strongly induced expression and function of CXCR4 and reduced CCR1 and CCR5
      expression on immature DCs. In addition, DC treatment with Bet.-APE significantly
      reduced LPS-induced production of CXCL10/IP-10, CCL5/RANTES; induced
      CCL22/macrophage-derived chemokine; and did not significantly change release of
      CCL17/thymus and activation-regulated chemokine. At a functional level, Bet.-APE
      increased the capacity of LPS-stimulated DCs to attract Th2 cells, whereas the
      capacity to recruit Th1 cells was reduced. Bet.-APE significantly and dose
      dependently enhanced intracellular cAMP, suggesting that water-soluble factors
      from pollen grains bind a G(alphas)-protein-coupled receptor. E(1)-Phytoprostanes
      were identified to be one player in the Th2-polarizing potential of aqueous
      pollen extracts. In summary, our results demonstrate that pollen itself releases
      regulatory mediators which generate a Th2-promoting micromilieu with preferential
      recruitment of Th2 cells to the site of pollen exposure.

PMID- 17548599
TI  - Kruppel-like factor 2 controls T cell trafficking by activating L-selectin
      (CD62L) and sphingosine-1-phosphate receptor 1 transcription.
AB  - Kruppel-like factor 2 (KLF2) is a member of zinc-finger transcription factors.
      Based on its expression in naive and memory T cells and the activated phenotype
      of few T cells in mice lacking KLF2 in the lymphoid lineage, KLF2 is postulated
      to regulate T cell homeostasis by promoting cell quiescence. In this study, we
      show that in reporter gene assays KLF2 directly activates the promoters of both
      CD62L and sphingosine-1-phosphate receptor 1 (S1P1), whose expression is critical
      for T cell egress from the thymus and homing to the lymph nodes. Correspondingly,
      exogenous KLF2 expression in primary T cells significantly up-regulates both
      CD62L and S1P1. Following adoptive transfer, KLF2-transduced T cells are much
      more efficient in homing to lymphoid organs than nontransduced T cells. These
      findings suggest that KLF2 regulates T cell homeostasis at least partly by
      controlling CD62L and S1P1 expression, and therefore T cell egress from the
      thymus and circulation in the periphery.

PMID- 17548600
TI  - IL-21 promotes differentiation of naive CD8 T cells to a unique effector
      phenotype.
AB  - IL-21, the most recently described member of the common gamma-chain cytokine
      family, is produced by activated CD4 T cells, whereas CD8 T cells express the IL
      21 receptor. To investigate a possible role for IL-21 in the priming of naive CD8
      T cells, we examined responses of highly purified naive OT-I CD8 T cells to
      artificial APCs displaying Ag and B7-1 on their surface. We found that IL-21
      enhanced OT-I clonal expansion and supported development of cytotoxic effector
      function. High levels of IL-2 did not support development of effector functions,
      but IL-2 was required for optimal responses in the presence of IL-21. IL-12 and
      IFN-alpha have previously been shown to support naive CD8 T cell differentiation
      and acquisition of effector functions through a STAT4-dependent mechanism. Here,
      we show that IL-21 does not require STAT4 to stimulate development of cytolytic
      activity. Furthermore, IL-21 fails to induce IFN-gamma or IL-4 production and can
      partially block IL-12 induction of IFN-gamma production. CD8 T cells that
      differentiate in response to IL-21 have a distinct surface marker expression
      pattern and are characterized as CD44(high), PD-1(low), CD25(low), CD134(low),
      and CD137(low). Thus, IL-21 can provide a signal required by naive CD8 T cells to
      differentiate in response to Ag and costimulation, and the resulting effector
      cells represent a unique effector phenotype with highly effective cytolytic
      activity, but deficient capacity to secrete IFN-gamma.

PMID- 17548601
TI  - CD8+ T cell-mediated suppression of autoimmunity in a murine lupus model of
      peptide-induced immune tolerance depends on Foxp3 expression.
AB  - Systemic lupus erythematosus is an autoimmune disease caused by autoantibodies,
      including IgG anti-DNA. New Zealand Black/New Zealand White F(1) female mice, a
      model of spontaneous polygenic systemic lupus erythematosus, tolerized with an
      artificial peptide (pConsensus) based on anti-DNA IgG sequences containing MHC
      class I and class II T cell determinants, develop regulatory CD4+CD25+ T cells
      and CD8+ inhibitory T cells (CD8+ Ti), both of which suppress autoantibody
      production. CD8+ Ti inhibit primarily via secretion of TGF-beta. In the present
      study, we show that the inhibitory function of CD8+ T cells from tolerized mice
      is sustained for up to 8 wk and at all times depends on expression of Foxp3. Both
      CD28-positive and CD28-negative CD8+ T cells contain inhibitory cells, but the
      expression of mRNA for Foxp3 and for TGF-beta is higher and lasts longer in the
      CD28- subset. In vitro addition of TGF-beta (in the presence of IL-2) induces
      Foxp3 expression in a dose-response manner. Gene inhibition or blockade with
      small interfering RNA of Foxp3 abrogates the ability of the CD8+ Ti to inhibit
      anti-DNA production and the proliferation of CD4+ Th cells. Moreover, a
      significant correlation between expression of Foxp3 and ability of CD8+ Ti to
      secrete TGF-beta is observed. Therefore, CD8+ Ti in this system of tolerance are
      similar to CD4+CD25+ regulatory T cells in their dependence on expression of
      Foxp3, and there may be a bidirectional Foxp3/TGF-beta autocrine loop that
      determines the ability of the CD8+ T cells to control autoimmunity.

PMID- 17548602
TI  - Single-stranded RNA derived from HIV-1 serves as a potent activator of NK cells.
AB  - Persistent immune activation is a hallmark of chronic viremic HIV-1 infection.
      Activation of cells of the innate immune system, such as NK cells, occurs rapidly
      upon infection, and is sustained throughout the course of the disease. However,
      the precise underlying mechanism accounting for the persistent HIV-1-induced
      activation of NK cells is poorly understood. In this study, we assessed the role
      of uridine-rich ssRNA derived from the HIV-1 long terminal repeat (ssRNA40) on
      activation of NK cells via TLR7/8. Although dramatic activation of NK cells was
      observed following stimulation of PBMC with ssRNA40, negligible activation was
      observed following stimulation of purified NK cells despite their expression of
      TLR8 mRNA and protein. The functional activation of NK cells by this HIV-1
      encoded TLR7/8 ligand could not be reconstituted with exogenous IL-12, IFN-alpha,
      or TNF-alpha, but was critically dependent on the direct contact of NK cells with
      plasmacytoid dendritic cells or CD14(+) monocytes, indicating an important level
      of NK cell cross-talk and regulation by accessory cells during TLR-mediated
      activation. Coincubation of monocyte/plasmacytoid dendritic cells, NK cells, and
      ssRNA40 potentiated NK cell IFN-gamma secretion in response to MHC-devoid target
      cells. Studies using NK cells derived from individuals with chronic HIV-1
      infection demonstrated a reduction of NK cell responsiveness following
      stimulation with TLR ligands in viremic HIV-1 infection. These data demonstrate
      that HIV-1-derived TLR ligands can contribute to the immune activation of NK
      cells and may play an important role in HIV-1-associated immunopathogenesis and
      NK cell dysfunction observed during acute and chronic viremic HIV-1 infection.

PMID- 17548603
TI  - A kinetic and dynamic analysis of Foxp3 induced in T cells by TGF-beta.
AB  - TGF-beta induces Foxp3 expression in stimulated T cells. These Foxp3 cells
      (induced regulatory T cells (iTreg)) share functional and therapeutic properties
      with thymic-derived Foxp3 regulatory T cells (natural regulatory T cells
      (nTreg)). We performed a single-cell analysis to better characterize the
      regulation of Foxp3 in iTreg in vitro and assess their dynamics after transfer in
      vivo. TGF-beta up-regulated Foxp3 in CD4(+)Foxp3 T cells only when added within a
      2- to 3-day window of CD3/CD28 stimulation. Up to 90% conversion occurred,
      beginning after 1-2 days of treatment. Foxp3 expression strictly required TCR
      stimulation but not costimulation and was independent of cell cycling. Removal of
      TGF-beta led to a loss of Foxp3 expression after an approximately 4-day lag. Most
      iTreg transferred into wild-type mice down-regulated Foxp3 within 2 days, and
      these Foxp3 cells were concentrated in the blood, spleen, lung, and liver. Few of
      the Foxp3 cells were detected by 28 days after transfer. However, some Foxp3
      cells persisted even to this late time point, and these preferentially localized
      to the lymph nodes and bone marrow. CXCR4 was preferentially expressed on Foxp3
      iTreg within the bone marrow, and CD62L was preferentially expressed on those in
      the lymph nodes. Like transferred nTreg and in contrast with revertant Foxp3
      cells, Foxp3 iTreg retained CD25 and glucocorticoid-induced TNFR family-related
      gene. Thus, Foxp3 expression in naive-stimulated T cells is transient in vitro,
      dependent on TGF-beta activity within a highly restricted window after activation
      and continuous TGF-beta presence. In vivo, a subset of transferred iTreg persist
      long term, potentially providing a lasting source for regulatory activity after
      therapeutic administration.

PMID- 17548604
TI  - Down-regulation of E-cadherin in human bronchial epithelial cells leads to
      epidermal growth factor receptor-dependent Th2 cell-promoting activity.
AB  - Airway epithelial cells are well-known producers of thymus- and activation
      regulated chemokine (TARC), a Th2 cell-attracting chemokine that may play an
      important role in the development of allergic airway inflammation. However, the
      mechanism responsible for up-regulation of TARC in allergy is still unknown. In
      the asthmatic airways, loss of expression of the cell-cell contact molecule E
      cadherin and reduced epithelial barrier function has been observed, which may be
      the result of an inadequate repair response. Because E-cadherin also suppressed
      multiple signaling pathways, we studied whether disruption of E-cadherin-mediated
      cell contact may contribute to increased proallergic activity of epithelial
      cells, e.g., production of the chemokine TARC. We down-regulated E-cadherin in
      bronchial epithelial cells by small interference RNA and studied effects on
      electrical resistance, signaling pathways, and TARC expression (by electric cell
      substrate impedance sensing, immunodetection, immunofluorescent staining, and
      real-time PCR). Small interference RNA silencing of E-cadherin resulted in loss
      of E-cadherin-mediated junctions, enhanced phosphorylation of epidermal growth
      factor receptor (EGFR), and the downstream targets MEK/ERK-1/2 and p38 MAPK,
      finally resulting in up-regulation of TARC as well as thymic stromal
      lymphopoietin expression. The use of specific inhibitors revealed that the effect
      on TARC is mediated by EGFR-dependent activation of the MAPK pathways. In
      contrast to TARC, expression of the Th1/Treg cell-attracting chemokine RANTES was
      unaffected by E-cadherin down-regulation. In summary, we show that loss of E
      cadherin-mediated epithelial cell-cell contact by damaging stimuli, e.g.,
      allergens, may result in reduced suppression of EGFR-dependent signaling pathways
      and subsequent induction of Th2 cell-attracting molecule TARC. Thus, disruption
      of intercellular epithelial contacts may specifically promote Th2 cell
      recruitment in allergic asthma.

PMID- 17548605
TI  - Acute alcohol exposure exerts anti-inflammatory effects by inhibiting IkappaB
      kinase activity and p65 phosphorylation in human monocytes.
AB  - Acute alcohol use is associated with impaired immune responses and decreased
      proinflammatory cytokine production. Our earlier studies have shown that acute
      alcohol intake inhibits NF-kappaB DNA binding in an IkappaBalpha-independent
      manner. We report using human peripheral blood monocytes and Chinese hamster
      ovary cells transfected with CD14 cells that acute alcohol treatment in vitro
      exerts NF-kappaB inhibition by disrupting phosphorylation of p65.
      Immunoprecipitation of p65 and IkappaBalpha revealed that acute alcohol exposure
      for 1 h decreased NF-kappaB-IkappaBalpha complexes in the cytoplasm.
      Phosphorylation of p65 at Ser(536) is mediated by IkappaB kinase (IKK)beta and is
      required for NF-kappaB-dependent cellular responses. We show that acute alcohol
      treatment decreased LPS-induced IKKalpha and IKKbeta activity resulting in
      decreased phosphorylation of p65 at Ser(536). Furthermore, nuclear expression of
      IKKalpha increased after alcohol treatment, which may contribute to inhibition of
      NF-kappaB. Decreased phosphorylation of nuclear p65 at Ser(276) was likely not
      due to alcohol-induced inhibition of protein kinase A and mitogen- and stress
      activated protein kinase-1 activity. Although decreased IkappaBalpha
      phosphorylation after acute alcohol treatment was attributable to reduced IKKbeta
      activity, degradation of IkappaBalpha during alcohol exposure was IKKbeta
      independent. Alcohol-induced degradation of IkappaBalpha in the presence of a 26S
      proteasome inhibitor suggested proteasome-independent IkappaBalpha degradation.
      Collectively, our studies suggest that acute alcohol exposure modulates
      IkappaBalpha-independent NF-kappaB activity primarily by affecting
      phosphorylation of p65. These findings further implicate an important role for
      IKKbeta in the acute effects of alcohol in immune cells.

PMID- 17548606
TI  - OX40-mediated differentiation to effector function requires IL-2 receptor
      signaling but not CD28, CD40, IL-12Rbeta2, or T-bet.
AB  - Ag-specific CD4 T cells transferred into unirradiated Ag-bearing recipients
      proliferate, but survival and accumulation of proliferating cells is not
      extensive and the donor cells do not acquire effector functions. We previously
      showed that a single costimulatory signal delivered by an agonist Ab to OX40
      (CD134) promotes accumulation of proliferating cells and promotes differentiation
      to effector CD4 T cells capable of secreting IFN-gamma. In this study, we
      determined whether OX40 costimulation requires supporting costimulatory or
      differentiation signals to drive acquisition of effector T cell function. We
      report that OX40 engagement drives effector T cell differentiation in the absence
      of CD28 and CD40 signals. Two important regulators of Th1 differentiation, IL-12R
      and T-bet, also are not required for acquisition of effector function in CD4 T
      cells responsive to OX40 stimulation. Finally, we show that CD25-deficient CD4 T
      cells produce little IFN-gamma in the presence of OX40 costimulation compared
      with wild type, suggesting that IL-2R signaling is required for efficient OX40
      mediated differentiation to IFN-gamma secretion.

PMID- 17548607
TI  - Tumor-reactive CD4+ T cell responses to the melanoma-associated chondroitin
      sulphate proteoglycan in melanoma patients and healthy individuals in the absence
      of autoimmunity.
AB  - To avoid immune escape by down-regulation or loss of Ag by the tumor cells,
      target Ags are needed, which are important for the malignant phenotype and
      survival of the tumor. We could identify a CD4(+) T cell epitope derived from the
      human melanoma-associated chondroitin sulfate proteoglycan (MCSP) (also known as
      high m.w.-melanoma-associated Ag), which is strongly expressed on >90% of human
      melanoma lesions and is important for the motility and invasion of melanoma
      cells. However, MCSP is not strictly tumor specific, because it is also expressed
      in a variety of normal tissues. Therefore, self tolerance should prevent the
      induction of strong T cell responses against these Ags by vaccination strategies.
      In contrast, breaking self tolerance to this Ag by effectively manipulating the
      immune system might mediate antitumor responses, although it would bear the risk
      of autoimmunity. Surprisingly, we could readily isolate CD4(+) Th cells from the
      blood of a healthy donor-recognizing peptide MCSP(693-709) on HLA-DR11-expressing
      melanoma cells. Broad T cell reactivity against this Ag could be detected in the
      peripheral blood of both healthy donors and melanoma patients, without any
      apparent signs of autoimmune disease. In some patients, a decline of T cell
      reactivity was observed upon tumor progression. Our data indicate that CD4(+) T
      cells are capable of recognizing a membrane glycoprotein that is important in
      melanoma cell function, and it may be possible that the sizable reactivity to
      this Ag in most normal individuals contributes to immune surveillance against
      cancer.

PMID- 17548608
TI  - The loss of telomerase activity in highly differentiated CD8+CD28-CD27- T cells
      is associated with decreased Akt (Ser473) phosphorylation.
AB  - The enzyme telomerase is essential for maintaining the replicative capacity of
      memory T cells. Although CD28 costimulatory signals can up-regulate telomerase
      activity, human CD8(+) T cells lose CD28 expression after repeated activation.
      Nevertheless, telomerase is still inducible in CD8(+)CD28(-) T cells. To identify
      alternative costimulatory pathways that may be involved, we introduced chimeric
      receptors containing the signaling domains of CD28, CD27, CD137, CD134, and ICOS
      in series with the CD3 zeta (zeta) chain into primary human CD8(+) T cells.
      Although CD3 zeta-chain signals alone were ineffective, triggering of all the
      other constructs induced proliferation and telomerase activity. However, not all
      CD8(+)CD28(-) T cells could up-regulate this enzyme. The further fractionation of
      CD8(+)CD28(-) T cells into CD8(+)CD28(-) CD27(+) and CD8(+)CD28(-)CD27(-) subsets
      showed that the latter had significantly shorter telomeres and extremely poor
      telomerase activity. The restoration of CD28 signaling in CD8(+)CD28(-)CD27(-) T
      cells could not reverse the low telomerase activity that was not due to decreased
      expression of human telomerase reverse transcriptase, the enzyme catalytic
      subunit. Instead, the defect was associated with decreased phosphorylation of the
      kinase Akt, that phosphorylates human telomerase reverse transcriptase to induce
      telomerase activity. Furthermore, the defective Akt phosphorylation in these
      cells was specific for the Ser(473) but not the Thr(308) phosphorylation site of
      this molecule. Telomerase down-regulation in highly differentiated CD8(+)CD28(
      )CD27(-) T cells marks their inexorable progress toward a replicative end stage
      after activation. This limits the ability of memory CD8(+) T cells to be
      maintained by continuous proliferation in vivo.

PMID- 17548609
TI  - CD4+ T cells from simian immunodeficiency virus disease-resistant sooty mangabeys
      produce more IL-2 than cells from disease-susceptible species: involvement of
      p300 and CREB at the proximal IL-2 promoter in IL-2 up-regulation.
AB  - IL-2 is an important cytokine required for the physiological function of CD4(+) T
      cells. Immunological unresponsiveness-anergy- of CD4(+) T cells is characterized
      by the inability of these cells to synthesize IL-2. Both progressive HIV
      infection leading to AIDS in humans and SIV infection in rhesus macaques (RM) are
      associated with dysregulation of IL-2 synthesis. In certain nonhuman primate
      species, such as sooty mangabeys (SM), SIV infection does not lead to AIDS. We
      have shown that this is associated with the resistance of the CD4(+) T cells from
      SM to undergo anergy in vitro. In this study, we show that CD4(+) T cells from SM
      spontaneously synthesize 2- to 3-fold higher levels of IL-2 than corresponding
      cells from RM. Proximal IL-2 promoter constructs derived from SM show
      significantly higher activity than the RM-derived constructs in primary CD4(+) T
      cells, which is associated with an element at approximately nt -200. Activity of
      both constructs was up-regulated by p300 and down-regulated by CREB to a similar
      degree. Chromatin immunoprecipitation analysis showed significantly higher
      binding of p300 and lower binding of CREB to the SM promoter in vivo. Two single
      nucleotide substitutions present in the SM sequence around position -200 and -180
      seem to increase the affinity of these sites for the binding of transcription
      factors, one of which was identified as Oct-1. These unique characteristics of
      the proximal IL-2 promoter in SM therefore can represent one of the mechanisms
      contributing to the resistance of these cells to undergo anergy.

PMID- 17548610
TI  - Phenotypic and functional effects of heat shock protein 90 inhibition on
      dendritic cell.
AB  - The 90-kDa heat shock protein (Hsp90) plays an important role in conformational
      regulation of cellular proteins and thereby cellular signaling and function. As
      Hsp90 is considered a key component of immune function and its inhibition has
      become an important target for cancer therapy, we here evaluated the role of
      Hsp90 in human dendritic cell (DC) phenotype and function. Hsp90 inhibition
      significantly decreased cell surface expression of costimulatory (CD40, CD80,
      CD86), maturation (CD83), and MHC (HLA-A, B, C and HLA-DP, DQ, DR) markers in
      immature DC and mature DC and was associated with down-regulation of both RNA and
      intracellular protein expression. Importantly, Hsp90 inhibition significantly
      inhibited DC function. It decreased Ag uptake, processing, and presentation by
      immature DC, leading to reduced T cell proliferation in response to tetanus
      toxoid as a recall Ag. It also decreased the ability of mature DC to present Ag
      to T cells and secrete IL-12 as well as induce IFN-gamma secretion by allogeneic
      T cells. These data therefore demonstrate that Hsp90-mediated protein folding is
      required for DC function and, conversely, Hsp90 inhibition disrupts the DC
      function of significant relevance in the setting of clinical trials evaluating
      novel Hsp90 inhibitor therapy in cancer.

PMID- 17548611
TI  - Transcriptional targeting of B cells for induction of peripheral CD8 T cell
      tolerance.
AB  - Several mechanisms are in place to neutralize autoimmune CD8 T cells by tolerance
      induction. Developing self-specific CD8 T cells are eliminated in the thymus by
      Ag-presenting epithelial and dendritic cells (DCs). However, CD8 T cells escaping
      thymic central tolerance can also be inactivated by tolerance mechanisms in
      peripheral organs. In contrast to DCs, the role of B cells in generating CD8 T
      cell tolerance is not well-characterized. To investigate this question in more
      detail, we transcriptionally targeted Ag to B cells using B cell-specific
      retroviral vectors in vivo. Although Ag expression could be detected in B cells
      of thymus, lymph nodes, and spleen, B cells were unable to induce central
      tolerance of CD8 thymocytes. In contrast, in peripheral organs, we could identify
      clonal deletion and functional inhibition (anergy) of CD8 T cells as tolerance
      inducing mechanisms. Although Ag expressed by B cells was acquired and cross
      presented by DCs, B cells were also sufficient to tolerize CD8 T cells directly.
      These findings suggest exploitation of B cells for Ag-specific immunotherapy of
      CD8 T cell-mediated autoimmune diseases.

PMID- 17548612
TI  - Requirements for T lymphocyte migration in explanted lymph nodes.
AB  - Although the requirements for T lymphocyte homing to lymph nodes (LNs) are well
      studied, much less is known about the requirements for T lymphocyte locomotion
      within LNs. Imaging of murine T lymphocyte migration in explanted LNs using two
      photon laser-scanning fluorescence microscopy provides an opportunity to
      systematically study these requirements. We have developed a closed system for
      imaging an intact LN with controlled temperature, oxygenation, and perfusion
      rate. Naive T lymphocyte locomotion in the deep paracortex of the LN required a
      perfusion rate of >13 microm/s and a partial pressure of O(2) (pO(2)) of >7.4%.
      Naive T lymphocyte locomotion in the subcapsular region was 38% slower and had
      higher turning angles and arrest coefficients than naive T lymphocytes in the
      deep paracortex. T lymphocyte activation decreased the requirement for pO(2), but
      also decreased the speed of locomotion in the deep paracortex. Although CCR7(-/-)
      naive T cells displayed a small reduction in locomotion, systemic treatment with
      pertussis toxin reduced naive T lymphocyte speed by 59%, indicating a
      contribution of Galpha(i)-mediated signaling, but involvement of other G protein
      coupled receptors besides CCR7. Receptor knockouts or pharmacological inhibition
      in the adenosine, PG/lipoxygenase, lysophosphatidylcholine, and sphingosine-1
      phosphate pathways did not individually alter naive T cell migration. These data
      implicate pO(2), tissue architecture, and G-protein coupled receptor signaling in
      regulation of naive T lymphocyte migration in explanted LNs.

PMID- 17548613
TI  - Availability of a diversely avid CD8+ T cell repertoire specific for the
      subdominant HLA-A2-restricted HIV-1 Gag p2419-27 epitope.
AB  - HLA-A2-restricted CTL responses to immunodominant HIV-1 epitopes do not appear to
      be very effective in the control of viral replication in vivo. In this study, we
      studied human CD8+ T cell responses to the subdominant HLA-A2-restricted epitope
      TV9 (Gag p24(19-27), TLNAWVKVV) to explore the possibility of increasing its
      immune recognition. We confirmed in a cohort of 313 patients, infected by clade B
      or clade C viruses, that TV9 is rarely recognized. Of interest, the functional
      sensitivity of the TV9 response can be relatively high. The potential T cell
      repertoires for TV9 and the characteristics of constituent clonotypes were
      assessed by ex vivo priming of circulating CD8+ T cells from healthy seronegative
      donors. TV9-specific CTLs capable of suppressing viral replication in vitro were
      readily generated, suggesting that the cognate T cell repertoire is not limiting.
      However, these cultures contained multiple discrete populations with a range of
      binding avidities for the TV9 tetramer and correspondingly distinct functional
      dependencies on the CD8 coreceptor. The lack of dominant clonotypes was not
      affected by the stage of maturation of the priming dendritic cells. Cultures
      primed by dendritic cells transduced to present endogenous TV9 were also
      incapable of clonal maturation. Thus, a diffuse TCR repertoire appeared to be an
      intrinsic characteristic of TV9-specific responses. These data indicate that
      subdominance is not a function of poor immunogenicity, cognate TCR repertoire
      availability, or the potential avidity properties thereof, but rather suggest
      that useful responses to this epitope are suppressed by competing CD8+ T cell
      populations during HIV-1 infection.

PMID- 17548614
TI  - Negative regulation of TCR signaling by NF-kappaB2/p100.
AB  - The positive regulation of the NF-kappaB-signaling pathway in response to TCR
      stimulation has been well-studied. However, little is known about the negative
      regulation of this pathway in T cells. This negative regulation is crucial in
      controlling the duration of TCR signaling and preventing abnormal lymphocyte
      activation and proliferation. Therefore, understanding the negative regulation of
      TCR-mediated NF-kappaB signaling is essential in understanding the mechanisms
      involved in T cell function and homeostasis. TCR stimulation of human CD4+ T
      cells resulted in an increase in NF-kappaB2/p100 expression with no appreciable
      increase in p52, its cleavage product. Due to the presence of inhibitory ankyrin
      repeats in the unprocessed p100, this observation suggests that p100 may function
      as a negative regulator of the NF-kappaB pathway. Consistent with this
      hypothesis, ectopic expression of p100 inhibited TCR-mediated NF-kappaB activity
      and IL-2 production in Jurkat T cells. Conversely, knockdown of p100 expression
      enhanced NF-kappaB transcriptional activity and IL-2 production upon TCR
      activation. p100 inhibited the pathway by binding and sequestering Rel
      transcription factors in the cytoplasm without affecting the activity of the
      upstream IkappaB kinase. The kinetics and IkappaB kinase gamma/NF-kappaB
      essential modulator dependency of p100 induction suggest that NF-kappaB2/p100
      acts as a late-acting negative-feedback signaling molecule in the TCR-mediated NF
      kappaB pathway.

PMID- 17548615
TI  - TLR agonists selectively promote terminal plasma cell differentiation of B cell
      subsets specialized in thymus-independent responses.
AB  - Naive murine B cells are known to proliferate and differentiate in response to
      LPS or CpG, which bind to TLR4 and TLR9, respectively. However, the naive murine
      B cell compartment is heterogeneous and comprises four different B cell subsets:
      B-1a, B-1b, marginal zone (MZ), and follicular (FO) B cells. B-1a, B-1b, and MZ B
      cells are specialized in the response to thymus-independent Ag, and FO B cells
      are involved in the response to thymus-dependent Ag. This study was undertaken to
      compare those four naive B cell subsets for their responses to TLR agonists.
      Quantitative RT-PCR analysis revealed that expression of TLR transcripts differs
      quantitatively but not qualitatively from one subset to the other. All TLR
      agonists, with the exception of flagellin and poly(I:C), stimulate B cell
      proliferation whatever the subset considered. However, TLR ligation leads to
      massive differentiation of B-1 and MZ B cells into mature plasma cells (PC) but
      only marginally promotes PC differentiation of FO B cells. Moreover, TLR
      stimulation strongly up-regulates expression of Blimp-1 and XBP-1(S), two
      transcription factors known to be instrumental in PC differentiation, in B-1 and
      MZ B cells but not in FO B cells. Altogether, our findings suggest that B-1 and
      MZ B cells are poised to PC differentiation in response to the microbial
      environment and that TLR agonists can be instrumental in stimulating Ab-mediated
      innate immune protection during microbial infections.

PMID- 17548616
TI  - Small rho GTPases mediate tumor-induced inhibition of endocytic activity of
      dendritic cells.
AB  - The generation, maturation, and function of dendritic cells (DC) have been shown
      to be markedly compromised in the tumor microenvironment in animals and humans.
      However, the molecular mechanisms and intracellular pathways involved in the
      regulation of the DC system in cancer are not yet fully understood. Recently, we
      have reported on the role of the small Rho GTPase family members Cdc42, Rac1, and
      RhoA in regulating DC adherence, motility, and Ag presentation. To investigate
      involvement of small Rho GTPases in dysregulation of DC function by tumors, we
      next evaluated how Cdc42, Rac1, and RhoA regulated endocytic activity of DC in
      the tumor microenvironment. We revealed a decreased uptake of dextran 40 and
      polystyrene beads by DC generated in the presence of different tumor cell lines,
      including RM1 prostate, MC38 colon, 3LL lung, and B7E3 oral squamous cell
      carcinomas in vitro and by DC prepared from tumor-bearing mice ex vivo. Impaired
      endocytic activity of DC cocultured with tumor cells was associated with
      decreased levels of active Cdc42 and Rac1. Transduction of DC with the dominant
      negative Cdc42 and Rac1 genes also led to reduced phagocytosis and receptor
      mediated endocytosis. Furthermore, transduction of DC with the constitutively
      active Cdc42 and Rac1 genes restored endocytic activity of DC that was inhibited
      by the tumors. Thus, our results suggest that tumor-induced dysregulation of
      endocytic activity of DC is mediated by reduced activity of several members of
      the small Rho GTPase family, which might serve as new targets for improving the
      efficacy of DC vaccines.

PMID- 17548617
TI  - Exposure of myeloid dendritic cells to exogenous or endogenous IL-10 during
      maturation determines their longevity.
AB  - Dendritic cells (DC) are essential for the initiation of primary adaptive immune
      responses, and their functionality is strongly down-modulated by IL-10. Both
      innate and adaptive immune signals trigger the up-regulation of antiapoptotic Bcl
      2 family members to facilitate the survival of DCs after maturation. However,
      whether IL-10 alters the expression of apoptotic-related genes in maturing DCs
      has not been determined. In this study, we demonstrate that spontaneous apoptosis
      rapidly occurred in myeloid DCs exposed to exogenous IL-10 upon maturation.
      Microarray analysis indicates that IL-10 suppressed the induction of three
      antiapoptotic genes, bcl-2, bcl-x, and bfl-1, which was coincident with the
      increased sensitivity of mature DCs to spontaneous apoptosis. IL-10 markedly
      inhibited the accumulation of steady state Bcl-2 message and protein in myeloid
      DCs activated through TLRs or TNFR family members, whereas exogenous IL-10
      affected Bcl-x(L) expression in a moderate manner. In contrast, bcl-2 expression
      of plasmacytoid DCs was less sensitive to the effects of IL-10. We further show
      that autocrine IL-10 significantly limited the longevity of myeloid DCs and
      altered the expression kinetics of Bcl-2 but not Bcl-x(L) in maturing DCs. We
      conclude that the degree of IL-10 exposure and/or the level of endogenous IL-10
      production upon myeloid DC maturation play a critical role in determining DC
      longevity. This regulatory mechanism of IL-10 is associated with the dynamic
      control of antiapoptotic Bcl-2 proteins.

PMID- 17548618
TI  - Immunomodulatory effects of viral TLR ligands on experimental asthma depend on
      the additive effects of IL-12 and IL-10.
AB  - Based on epidemiological data, the hygiene hypothesis associates poor hygienic
      living conditions during childhood with a lower risk for the development of
      allergic diseases such as bronchial asthma. The role of viral infections, and
      especially of viral TLR ligands, within this context remains to be clarified.
      Viral TLR ligands involve dsRNA and ssRNA which are recognized by TLR-3 or TLR-7,
      respectively. In this study, we evaluated the impact of TLR-3 or TLR-7 activation
      on experimental asthma in mice. Systemic application of the synthetic TLR-3 or
      TLR-7 ligands polycytidylic-polyinosinic acid (p(I:C)) or R-848, respectively,
      during the sensitization phase prevented the production of OVA-specific IgE and
      IgG1 Abs and subsequently abolished all features of experimental asthma including
      airway hyperresponsiveness and allergic airway inflammation. Furthermore,
      administration of p(I:C) or R-848 to animals with already established primary
      allergic responses revealed a markedly reduced secondary response following
      allergen aerosol rechallenges. In contrast to wild-type animals, application of
      p(I:C) or R-848 to IL-12p35(-/-) mice had no effect on airway inflammation,
      goblet cell hyperplasia, and airway hyperresponsiveness. However, in the absence
      of IL-12, the numbers of eosinophils and lymphocytes in bronchoalveolar lavage
      fluids were still significantly reduced. These partial effects could also be
      abolished by neutralizing anti-IL-10 Abs in IL-12p35(-/-) mice. These data
      indicate that TLR-3 or TLR-7 activation by viral TLR ligands has both preventive
      as well as suppressive effects on experimental asthma which is mediated by the
      additive effects of IL-12 and IL-10.

PMID- 17548619
TI  - Protein kinase Cdelta regulates antigen receptor-induced lytic granule
      polarization in mouse CD8+ CTL.
AB  - Lytic granule exocytosis is the major pathway used by CD8+ CTL to kill virally
      infected and tumor cells. Despite the obvious importance of this pathway in
      adaptive T cell immunity, the molecular identity of enzymes involved in the
      regulation of this process is poorly characterized. One signal known to be
      critical for the regulation of granule exocytosis-mediated cytotoxicity in CD8+ T
      cells is Ag receptor-induced activation of protein kinase C (PKC). However, it is
      not known which step of the process is regulated by PKC. In addition, it has not
      been determined to date which of the PKC family members is required for the
      regulation of lytic granule exocytosis. By combination of pharmacological
      inhibitors and use of mice with targeted gene deletions, we show that PKCdelta is
      required for granule exocytosis-mediated lytic function in mouse CD8+ T cells.
      Our studies demonstrate that PKCdelta is required for lytic granule exocytosis,
      but is dispensable for activation, cytokine production, and expression of
      cytolytic molecules in response to TCR stimulation. Importantly, defective lytic
      function in PKCdelta-deficient cytotoxic lymphocytes is reversed by ectopic
      expression of PKCdelta. Finally, we show that PKCdelta is not involved in target
      cell-induced reorientation of the microtubule-organizing center, but is required
      for the subsequent exocytosis step, i.e., lytic granule polarization. Thus, our
      studies identify PKCdelta as a novel and selective regulator of Ag receptor
      induced lytic granule polarization in mouse CD8+ T cells.

PMID- 17548620
TI  - Expression of the voltage-gated sodium channel NaV1.5 in the macrophage late
      endosome regulates endosomal acidification.
AB  - Voltage-gated sodium channels expressed on the plasma membrane activate rapidly
      in response to changes in membrane potential in cells with excitable membranes
      such as muscle and neurons. Macrophages also require rapid signaling mechanisms
      as the first line of defense against invasion by microorganisms. In this study,
      our goal was to examine the role of intracellular voltage-gated sodium channels
      in macrophage function. We demonstrate that the cardiac voltage-gated sodium
      channel, NaV1.5, is expressed on the late endosome, but not the plasma membrane,
      in a human monocytic cell line, THP-1, and primary human monocyte-derived
      macrophages. Although the neuronal channel, NaV1.6, is also expressed
      intracellularly, it has a distinct subcellular localization. In primed cells,
      NaV1.5 regulates phagocytosis and endosomal pH during LPS-mediated endosomal
      acidification. Activation of the endosomal channel causes sodium efflux and
      decreased intraendosomal pH. These results demonstrate a functionally relevant
      intracellular voltage-gated sodium channel and reveal a novel mechanism to
      regulate macrophage endosomal acidification.

PMID- 17548621
TI  - Identification and characterization of novel bone marrow myeloid DEC205+Gr-1+
      cell subsets that differentially express chemokine and TLRs.
AB  - Bone marrow-derived immunomodulatory cytokines impart a critical function in the
      regulation of innate immune responses and hemopoiesis. However, the source of
      immunomodulatory cytokines in murine bone marrow and the cellular immune
      mechanisms that control local cytokine secretion remain poorly defined. Herein,
      we identified a population of resident murine bone marrow myeloid DEC205(+)CD11c(
      )B220(-)Gr1(+)CD8alpha(-)CD11b(+) cells that respond to TLR2, TLR4, TLR7, TLR8,
      and TLR9 agonists as measured by the secretion of proinflammatory and anti
      inflammatory cytokines in vitro. Phenotypic and functional analyses revealed that
      DEC205(+)CD11b(+)Gr-1(+) bone marrow cells consist of heterogeneous populations
      of myeloid cells that can be divided into two main cell subsets based on
      chemokine and TLR gene expression profile. The DEC205(+)CD11b(+)Gr-1(low) cell
      subset expresses high levels of TLR7 and TLR9 and was the predominant source of
      IL-6, TNF-alpha, and IL-12 p70 production following stimulation with the TLR7 and
      TLR9 agonists CpG and R848, respectively. In contrast, the DEC205(+)CD11b(+)Gr
      1(high) cell subset did not respond to CpG and R848 stimulation, which correlated
      with their lack of TLR7 and TLR9 expression. Similarly, a differential chemokine
      receptor expression profile was observed with higher expression of CCR1 and CXCR2
      found in the DEC205(+)CD11(+)Gr-1(high) cell subset. Thus, we identified a
      previously uncharacterized population of resident bone marrow cells that may be
      implicated in the regulation of local immune responses in the bone marrow.

PMID- 17548622
TI  - IgG opsonization of HIV impedes provirus formation in and infection of dendritic
      cells and subsequent long-term transfer to T cells.
AB  - Already at initial phases of infection, HIV is coated with complement fragments.
      During the chronic phase, when HIV-specific IgGs appear, the virus circulates
      immune complexed with IgG and complement. Thus, we studied the interaction of
      dendritic cells (DCs) and DC-T cell cocultures with complement (C)-opsonized and
      C-IgG-opsonized HIV. HIV infection of monocyte-derived DCs and circulating BDCA-1
      positive DCs was significantly reduced upon the presence of virus-specific but
      non-neutralizing IgGs. DCs exposed to C-Ig-HIV or IgG-opsonized HIV showed an
      impaired provirus formation and p24 production and a decreased transmission rate
      to autologous nonstimulated T cells upon migration along a chemokine gradient.
      This reduced infectivity was also observed in long-term experiments, when T cells
      were added delayed to DCs exposed to IgG-coated HIV without migration. Similar
      kinetics were seen when sera from HIV-1-infected individuals before and after
      seroconversion were used in infection assays. Both C- and C-IgG-opsonized HIV
      were captured and targeted to a tetraspanin-rich endosome in immature DCs, but
      differed with respect to MHC class II colocalization. The reduced infection by
      IgG-opsonized HIV is possibly due to interactions of virus-bound IgG with
      FcgammaRIIb expressed on DCs. Therefore, the intracellular fate and transmission
      of immune-complexed HIV seems to differ depending on time and opsonization
      pattern.

PMID- 17548623
TI  - Low-dose peptide tolerance therapy of lupus generates plasmacytoid dendritic
      cells that cause expansion of autoantigen-specific regulatory T cells and
      contraction of inflammatory Th17 cells.
AB  - Subnanomolar doses of an unaltered, naturally occurring nucleosomal histone
      peptide epitope, H4(71-94), when injected s.c. into lupus-prone mice, markedly
      prolong lifespan by generating CD4+25+ and CD8+ regulatory T cells (Treg)
      producing TGF-beta. The induced Treg cells suppress nuclear autoantigen-specific
      Th and B cells and block renal inflammation. Splenic dendritic cells (DC)
      captured the s.c.-injected H4(71-94) peptide rapidly and expressed a tolerogenic
      phenotype. The DC of the tolerized animal, especially plasmacytoid DC, produced
      increased amounts of TGF-beta, but diminished IL-6 on stimulation via the TLR-9
      pathway by nucleosome autoantigen and other ligands; and those plasmacytoid DC
      blocked lupus autoimmune disease by simultaneously inducing autoantigen-specific
      Treg and suppressing inflammatory Th17 cells that infiltrated the kidneys of
      untreated lupus mice. Low-dose tolerance with H4(71-94) was effective even though
      the lupus immune system is spontaneously preprimed to react to the autoepitope.
      Thus, H4(71-94) peptide tolerance therapy that preferentially targets pathogenic
      autoimmune cells could spare lupus patients from chronically receiving toxic
      agents or global immunosuppressants and maintain remission by restoring
      autoantigen-specific Treg cells.

PMID- 17548624
TI  - Follicular dendritic cell secreted protein (FDC-SP) regulates germinal center and
      antibody responses.
AB  - We previously identified follicular dendritic cell secreted protein (FDC-SP), a
      small secreted protein of unknown function expressed in human tonsillar germinal
      centers (GC). To assess potential in vivo activities of FDC-SP, transgenic mice
      were generated to constitutively express FDC-SP in lymphoid tissues. FDC-SP
      transgenic mice show relatively normal development of immune cell populations,
      with the exception of a small increase in mature follicular B cells, and normal
      lymphoid tissue architecture. Upon immunization with a T-dependent Ag, FDC-SP
      transgenic mice were capable of producing an Ag-specific Ab; however, the titers
      of Ag-specific IgG2a and IgE were significantly reduced. GC responses after
      immunization were markedly diminished, with transgenic mice showing decreased
      numbers and sizes of GCs but normal development of follicular dendritic cell
      networks and normal positioning of GCs. FDC-SP transgenic mice also showed
      reduced production of Ag-specific IgG3 Ab after immunization with a type II T
      independent Ag, suggesting that the FDC-SP can also regulate the induction of B
      cell responses outside the GC. Purified FDC-SP transgenic B cells function
      normally in vitro, with the exception of blunted chemotaxis responses to CXCL12
      and CXCL13. FDC-SP can induce the chemotaxis of CD40-stimulated nontransgenic B
      cells and can significantly enhance B cell migration in combination with
      chemokines, indicating that FDC-SP may function in part by regulating B cell
      chemotaxis. These results provide the first evidence for immunomodulatory
      activities of FDC-SP and implicate this molecule as a regulator of B cell
      responses.

PMID- 17548625
TI  - Novel suppressive function of transitional 2 B cells in experimental arthritis.
AB  - The immune system contains natural regulatory cells important in the maintenance
      of tolerance. Although this suppressive function is usually attributed to CD4
      regulatory T cells, recent reports have revealed an immunoregulatory role for IL
      10-producing B cells in the context of several autoimmune diseases including
      collagen-induced arthritis. In the present study, we attribute this suppressive
      function to a B cell subset expressing high levels of CD21, CD23, and IgM,
      previously identified as transitional 2-marginal zone precursor (T2-MZP) B cells.
      T2-MZP B cells are present in the spleens of naive mice and increase during the
      remission phase of arthritis. Following adoptive transfer to immunized DBA/1
      mice, T2-MZP B cells significantly prevented new disease and ameliorated
      established disease. The suppressive effect on arthritis was paralleled by an
      inhibition of Ag-specific T cell activation and a reduction in cells exhibiting
      Th1-type functional responses. We also provide evidence that this regulatory
      subset mediates its suppression through the secretion of suppressive cytokines
      and not by cell-to-cell contact. The ability to regulate an established immune
      response by T2-MZP B cells endows this subset of B cells with a striking and
      previously unrecognized immunoregulatory potential.

PMID- 17548626
TI  - Coexpression of IL-5 and eotaxin-2 in mice creates an eosinophil-dependent model
      of respiratory inflammation with characteristics of severe asthma.
AB  - Mouse models of allergen provocation and/or transgenic gene expression have
      provided significant insights regarding the cellular, molecular, and immune
      responses linked to the pathologies occurring as a result of allergic respiratory
      inflammation. Nonetheless, the inability to replicate the eosinophil activities
      occurring in patients with asthma has limited their usefulness to understand the
      larger role(s) of eosinophils in disease pathologies. These limitations have led
      us to develop an allergen-naive double transgenic mouse model that expresses IL-5
      systemically from mature T cells and eotaxin-2 locally from lung epithelial
      cells. We show that these mice develop several pulmonary pathologies
      representative of severe asthma, including structural remodeling events such as
      epithelial desquamation and mucus hypersecretion leading to airway obstruction,
      subepithelial fibrosis, airway smooth muscle hyperplasia, and pathophysiological
      changes exemplified by exacerbated methacholine-induced airway
      hyperresponsiveness. More importantly, and similar to human patients, the
      pulmonary pathologies observed are accompanied by extensive eosinophil
      degranulation. Genetic ablation of all eosinophils from this double transgenic
      model abolished the induced pulmonary pathologies, demonstrating that these
      pathologies are a consequence of one or more eosinophil effector functions.

PMID- 17548627
TI  - A quantitative analysis of the variables affecting the repertoire of T cell
      specificities recognized after vaccinia virus infection.
AB  - Many components contribute to immunodominance in the response to a complex virus,
      but their relative importance is unclear. This was addressed using vaccinia virus
      and HLA-A*0201 as the model system. A comprehensive analysis of 18 viral proteins
      recognized by CD8(+) T cell responses demonstrated that approximately one
      fortieth of all possible 9- to 10-mer peptides were high-affinity HLA-A*0201
      binders. Peptide immunization and T cell recognition data generated from 90
      peptides indicated that about one-half of the binders were capable of eliciting T
      cell responses, and that one-seventh of immunogenic peptides are generated by
      natural processing. Based on these results, we estimate that vaccinia virus
      encodes approximately 150 dominant and subdominant epitopes restricted in by HLA
      A*0201. However, of all these potential epitopes, only 15 are immunodominant and
      actually recognized in vivo during vaccinia virus infection of HLA-A*0201
      transgenic mice. Neither peptide-binding affinity, nor complex stability, nor TCR
      avidity, nor amount of processed epitope appeared to strictly correlate with
      immunodominance status. Additional experiments suggested that vaccinia infection
      impairs the development of responses directed against subdominant epitopes. This
      suggested that additional factors, including immunoregulatory mechanisms,
      restrict the repertoire of T cell specificities after vaccinia infection by a
      factor of at least 10.

PMID- 17548628
TI  - C5a-blockade improves burn-induced cardiac dysfunction.
AB  - We previously reported that generation of the anaphylatoxin C5a is linked to the
      development of cardiac dysfunction in sepsis due to C5a interaction with its
      receptor (C5aR) on cardiomyocytes. Burn injury involves inflammatory mechanisms
      that can lead to C5a generation as well. In this study, we investigated the
      effects of C5a blockade on burn-induced cardiac dysfunction. Using a standardized
      rat model of full thickness scald injury, left ventricular pressures were
      recorded in vivo followed by in vitro assessment of sarcomere contraction of
      single cardiomyocytes. Left ventricular pressures in vivo and cardiomyocyte
      sarcomere contractility in vitro were significantly reduced following burn
      injury. In the presence of anti-C5a Ab, these defects were greatly attenuated 1,
      6, and 12 h after burn injury and completely abolished 24 h after burn. In vitro
      incubation of cardiomyocytes with bacterial LPS accentuated the impaired
      contractility, which was partially prevented in cardiomyocytes from burned rats
      that had received an anti-C5a Ab. Based on Western blot analyses, real-time PCR,
      and immunostaining of left ventricular heart tissue, there was a significant
      increase in cardiomyocyte expression of C5aR after burn injury. In conclusion, an
      in vivo blockade of C5a attenuates burn-induced cardiac dysfunction. Further
      deterioration of contractility due to the exposure of cardiomyocytes to LPS was
      partially prevented by C5a-blockade. These results suggest a linkage between C5a
      and burn-induced cardiac dysfunction and a possible contribution of LPS to these
      events.

PMID- 17548629
TI  - RNA interference elucidates the role of focal adhesion kinase in HLA class I
      mediated focal adhesion complex formation and proliferation in human endothelial
      cells.
AB  - Ligation of class I molecules by anti-HLA Ab stimulates an intracellular
      signaling cascade resulting in endothelial cell (EC) survival and proliferation,
      and has been implicated in the process of chronic allograft rejection and
      transplant-associated vasculopathy. In this study, we used small interfering RNA
      blockade of focal adhesion kinase (FAK) protein to determine its role in class I
      mediated organization of the actin cytoskeleton, cell survival, and cell
      proliferation in primary cultures of human aortic EC. Knockdown of FAK
      appreciably inhibited class I-mediated phosphorylation of Src at Tyr(418), p85
      PI3K, and Akt at both Thr(308) and Ser(473) sites. FAK knockdown also reduced
      class I-mediated phosphorylation of paxillin at Try(118) and blocked class I
      induced paxillin assembly into focal contacts. FAK small interfering RNA
      completely abrogated class I-mediated formation of actin stress fibers.
      Interestingly, FAK knockdown did not modify fibroblast growth factor receptor
      expression induced by class I ligation. However, FAK knockdown blocked HLA class
      I-stimulated cell cycle proliferation in the presence and absence of basic
      fibroblast growth factor. This study shows that FAK plays a critical role in
      class I-induced cell proliferation, cell survival, and focal adhesion assembly in
      EC and may promote the development of transplant-associated vasculopathy.

PMID- 17548630
TI  - Paratope plasticity in diverse modes facilitates molecular mimicry in antibody
      response.
AB  - The immune response against methyl-alpha-D-mannopyranoside mimicking 12-mer
      peptide (DVFYPYPYASGS) was analyzed at the molecular level towards understanding
      the equivalence of these otherwise disparate Ags. The Ab 7C4 recognized the
      immunizing peptide and its mimicking carbohydrate Ag with comparable affinities.
      Thermodynamic analyses of the binding interactions of both molecules suggested
      that the mAb 7C4 paratope lacks substantial conformational flexibility, an
      obvious possibility for facilitating binding to chemically dissimilar Ags.
      Favorable changes in entropy during binding indicated the importance of
      hydrophobic interactions in recognition of the mimicking carbohydrate Ag. Indeed,
      the topology of the Ag-combining site was dominated by a cluster of aromatic
      residues, contributed primarily by the specificity defining CDR H3. Epitope
      mapping analysis demonstrated the critical role of three aromatic residues of the
      12-mer in binding to the Ab. Our studies delineate a mechanism by which mimicry
      is manifested in the absence of either structural similarity of the epitopes or
      conformational flexibility in the paratope. An alternate mode of recognition of
      dissimilar yet mimicking Ags by the anti-peptide Ab involves plasticity
      associated with aromatic/hydrophobic and van der Waals interactions. Thus,
      antigenic mimicry may be a consequence of paratope-specific modulations rather
      than being dependent only on the properties of the epitope. Such modulations may
      have evolved toward minimizing the consequences of antigenic variation by
      invading pathogens.

PMID- 17548631
TI  - A transporter associated with antigen-processing independent vacuolar pathway for
      the MHC class I-mediated presentation of endogenous transmembrane proteins.
AB  - MHC class I molecules present peptides derived from the ectodomains of endogenous
      transmembrane proteins; however, the processing of these Ags is incompletely
      understood. As model transmembrane Ags we investigated the processing of MHC-I
      derived fusion proteins containing the N-terminally extended K(b)-restricted OVA
      epitope SIINFEKL in the extracytoplasmic domain. In TAP-deficient,
      nonprofessional APCs, the epitope was cleaved out of various sequence contexts
      and presented to T cells. Ag presentation was inhibited by acidophilic amines and
      inhibitors of the vacuolar proton pump, indicating processing in endosomes.
      Endosomal aspartic-type cathepsins, and to some extent also the trans-Golgi
      network protease furin, were involved in processing. Clathrin-dependent and
      independent internalization from the cell surface targeted MHC-I fusion proteins
      to early and late endosomes, where SIINFEKL/K(b) complexes were detected by
      immunofluorescence microscopy. Targeting of MHC-I fusion proteins to processing
      compartments was independent of sequence motifs in the cytoplasmic tail. Not only
      TAP-deficient cells, but also TAP-competent APCs used the vacuolar pathway for
      processing of MHC-I fusion proteins. Thus, endosomal processing of internalized
      endogenous transmembrane proteins represents a novel alternate pathway for the
      generation of MHC-I-binding peptides.

PMID- 17548632
TI  - Episodes of natural selection shaped the interactions of IgA-Fc with FcalphaRI
      and bacterial decoy proteins.
AB  - FcalphaRI, a receptor for IgA-Fc, recruits myeloid cells to attack IgA-coated
      pathogens. By competing with FcalphaRI for IgA, bacterial decoys, like SSL7 of
      Staphylococcus aureus, subvert this defense. We examined how pathogen selection
      has driven the diversification and coevolution of IgA and FcalphaRI. In higher
      primates, the IgA binding site of FcalphaRI diversified under positive selection,
      a strong episode occurring in hominoid ancestors about the time of the IgA gene
      duplication. The differential binding of SSL7 to IgA-Fc of different species
      correlates with substitution at seven positions in IgA-Fc, two of which were
      positively selected in higher primates. Two others, which reduce SSL7 binding,
      emerged during episodes of positive selection in the rabbit and rodent lineages.
      The FcalphaRI-IgA interaction evolves episodically under two types of positive
      selection: pressure from pathogen decoys selects for IgA escape variants which,
      in turn, selects for FcalphaRI variants to keep up with the novel IgA. When
      FcalphaRI cannot keep up, its function is lost and the gene becomes susceptible
      to elimination, as occurred in the mouse genome, either by chance or selection on
      one of the many linked, variable immune system genes. A cluster of positively
      selected residues presents a putative binding site for unknown IgA-binding
      factors.

PMID- 17548633
TI  - Early diversification of the TNF superfamily in teleosts: genomic
      characterization and expression analysis.
AB  - The TNF superfamily (TNFSF) of proteins are cytokines involved in diverse
      immunological and developmental pathways. Little is known about their evolution
      or expression in lower vertebrate species. Bioinformatic searches of Zebrafish,
      Tetraodon, and Fugu genome and other teleost expressed sequence tag databases
      identified 44 novel gene sequences containing a TNF homology domain. This work
      reveals the following: 1) teleosts possess orthologs of BAFF, APRIL, EDA, TWEAK,
      4-1BBL, Fas ligand, LIGHT, CD40L, RANKL, and possibly TL1A; 2) the BAFF-APRIL
      subfamily is enriched by a third member, BALM, unique to fish; 3) orthologs of
      lymphotoxins alpha and beta were not clearly identified in teleosts and are
      substituted by a related ligand, TNF-New; 4) as many as four TRAIL-like genes are
      present in teleosts, as compared with only one in mammals; and 5) T cell
      activation ligands OX40L, CD27L, CD30L, and GITRL were not identified in any fish
      species. Finally, we characterize mRNA expression of TNFSF members CD40L, LIGHT,
      BALM, APRIL, Fas ligand, RANKL, TRAIL-like, and TNF-New in rainbow trout,
      Oncorhynchus mykiss, immune and nonimmune tissues. In conclusion, we identified a
      total of 14 distinct TNFSF members in fishes, indicating expansion of this
      superfamily before the divergence of bony fish and tetrapods, approximately 360
      450 million years ago. Based on these findings, we extend a model of TNFSF
      evolution and the co-emergence of the vertebrate adaptive immune system.

PMID- 17548634
TI  - IL-10 regulates movement of intestinally derived CD4+ T cells to the liver.
AB  - Diseases that affect the intestine may have hepatic manifestations, but the
      mechanisms involved in establishing hepatic disease secondarily remain poorly
      understood. We previously reported that IL-10 knockout (KO) mice developed severe
      necrotizing hepatitis following oral infection with Trichinella spiralis. In this
      study, we used this model of intestinal inflammation to further examine the role
      of IL-10 in regulating hepatic injury. Hepatic damage was induced by migrating
      newborn larvae. By delivering the parasite directly into the portal vein, we
      demonstrated that an ongoing intestinal immune response was necessary for the
      development of hepatitis. Intestinally derived CD4+ cells increased in the livers
      of IL-10 KO mice, and Ab-mediated blockade of MAdCAM-1 inhibited the accumulation
      of CD4+alpha(4)beta(7)+ cells in the liver. Moreover, adoptive transfer of
      intestinally primed CD4+ T cells from IL-10 KO mice caused hepatitis in infected
      immunodeficient animals. Conversely, transfer of wild-type donor cells reduced
      the severity of hepatic inflammation in IL-10 KO recipients, demonstrating
      regulatory activity. Our results revealed that IL-10 prevented migration of
      intestinal T cells to the liver and inhibited the development of hepatitis.

PMID- 17548635
TI  - Dendritic cells derived from murine colonic mucosa have unique functional and
      phenotypic characteristics.
AB  - Dendritic cells (DCs) residing in different tissues and exposed to different
      organisms are likely to have different reactivities to their surrounding
      environment. Many studies use in vitro generated DCs to examine functions of
      these cells, but such cells may not truly reflect the nature of DCs and their in
      situ activities in vivo. We have used magnetic label-based technique to isolate
      colonic DCs to conduct derailed characterization of these cells. Colonic DCs
      comprise mainly CD11b+ DCs with few CD8alpha+ DCs or plasmacytoid DCs.
      Functionally, isolated colonic DCs are able to endocytose and process proteins,
      undergo maturation, and stimulate T cells to proliferate. Importantly, expression
      of TLRs by colonic DCs is significantly lower than that of their spleen
      counterparts; however, they appear to be as, or more, responsive to stimulation
      by oligodeoxynucleotides containing CpG motif based on their cytokine production.
      We speculate that colonic DCs have unique reactivities differing from DCs
      residing in other lymphoid tissues and are adapted for the unique
      microenvironment of the colonic mucosa and that these cells react uniquely to
      their environment.

PMID- 17548636
TI  - Lung dendritic cells rapidly mediate anthrax spore entry through the pulmonary
      route.
AB  - Inhalational anthrax is a life-threatening infectious disease of considerable
      concern, especially because anthrax is an emerging bioterrorism agent. The exact
      mechanisms leading to a severe clinical form through the inhalational route are
      still unclear, particularly how immobile spores are captured in the alveoli and
      transported to the lymph nodes in the early steps of infection. We investigated
      the roles of alveolar macrophages and lung dendritic cells (LDC) in spore
      migration. We demonstrate that alveolar macrophages are the first cells to
      phagocytose alveolar spores, and do so within 10 min. However, interstitial LDCs
      capture spores present in the alveoli within 30 min without crossing the
      epithelial barrier suggesting a specific mechanism for rapid alveolus sampling by
      transepithelial extension. We show that interstitial LDCs constitute the cell
      population that transports spores into the thoracic lymph nodes from within 30
      min to 72 h after intranasal infection. Our results demonstrate that LDCs are
      central to spore transport immediately after infection. The rapid kinetics of
      pathogen transport may contribute to the clinical features of inhalational
      anthrax.

PMID- 17548637
TI  - Depletion of CD8+ cells in sooty mangabey monkeys naturally infected with simian
      immunodeficiency virus reveals limited role for immune control of virus
      replication in a natural host species.
AB  - SIV infection of sooty mangabeys (SMs), a natural host species, does not cause
      AIDS despite high-level virus replication. In contrast, SIV infection of
      nonnatural hosts such as rhesus macaques (RMs) induces an AIDS-like disease. The
      depletion of CD8+ T cells during SIV infection of RMs results in marked increases
      in plasma viremia, suggesting a key role for CD8+ T cells in controlling levels
      of SIV replication. To assess the role that CD8+ T cells play in determining the
      virologic and immunologic features of nonpathogenic SIV infection in SMs, we
      transiently depleted CD8+ T cells in SIV-infected and uninfected SMs using a
      CD8alpha-specific Ab (OKT8F) previously used in studies of SIV-infected RMs.
      Treatment of SMs with the OKT8F Ab resulted in the prompt and profound depletion
      of CD8+ T cells. However, in contrast to CD8+ cell depleted, SIV-infected RMs,
      only minor changes in the levels of plasma viremia were observed in most SIV
      infected SMs during the period of CD8+ cell deficiency. Those SMs demonstrating
      greater increases in SIV replication following CD8+ cell depletion also displayed
      higher levels of CD4+ T cell activation and/or evidence of CMV reactivation,
      suggesting that an expanded target cell pool rather than the absence of CD8+ T
      cell control may have been primarily responsible for transient increases in
      viremia. These data indicate that CD8+ T cells exert a limited influence in
      determining the levels of SIV replication in SMs and provide additional evidence
      demonstrating that the absence of AIDS in SIV-infected SMs is not due to the
      effective control of viral replication by cellular immune responses.

PMID- 17548638
TI  - Macrophage-inflammatory protein-3alpha mediates epidermal growth factor receptor
      transactivation and ERK1/2 MAPK signaling in Caco-2 colonic epithelial cells via
      metalloproteinase-dependent release of amphiregulin.
AB  - Previously, we reported that normal colonocytes produce the memory CD4(+) T cell
      directed chemokine MIP-3alpha, and that epithelial MIP-3alpha levels are elevated
      in inflammatory bowel disease. Interestingly, the unique receptor for MIP-3alpha,
      CCR6, is expressed by a variety of cell types including colonocytes, suggesting
      that MIP-3alpha may regulate additional biological activities in the intestine.
      The aim of this study was to determine whether MIP-3alpha can induce intestinal
      epithelial cell proliferation and to examine the signaling mechanisms that
      mediate this response. We show that nonstimulated Caco-2 and HT-29 colonic
      epithelial cells express CCR6, and that stimulation of Caco-2 cells by MIP-3alpha
      can dose dependently increase cell proliferation as well as activate the
      epidermal growth factor receptor (EGFR) and ERK1/2 MAPK. MIP-3alpha-mediated
      ERK1/2 activation in Caco-2 cells appeared to require metalloproteinase-dependent
      release of the endogenous EGFR ligand amphiregulin and transactivation of the
      EGFR. Moreover, blockade of amphiregulin bioactivity using a neutralizing
      polyclonal Ab significantly reduced MIP-3alpha-mediated, but not EGF-mediated
      Caco-2 cell proliferation. Taken together, our findings indicate that MIP-3alpha
      can regulate mitogenic signaling in colonic epithelial cells and thus may serve
      an important homeostatic function in the intestine by regulating tissue turnover
      and maintenance of the epithelium, in addition to its role in regulating
      leukocyte recruitment.

PMID- 17548639
TI  - The Nod-like receptor family member Naip5/Birc1e restricts Legionella pneumophila
      growth independently of caspase-1 activation.
AB  - Similar to Ipaf and caspase-1, the Nod-like receptor protein Naip5 restricts
      intracellular proliferation of Legionella pneumophila, the causative agent of a
      severe form of pneumonia known as Legionnaires' disease. Thus, Naip5 has been
      suggested to regulate Legionella replication inside macrophages through the
      activation of caspase-1. In this study, we show that cytosolic delivery of
      recombinant flagellin activated caspase-1 in A/J macrophages carrying a mutant
      Naip5 allele, and in C57BL/6 (B6) macrophages congenic for the mutant Naip5
      allele (B6-Naip5(A/J)), but not in Ipaf(-/-) cells. In line with these results,
      A/J and B6-Naip5(A/J) macrophages induced high levels of caspase-1 activation and
      IL-1beta secretion when infected with Legionella. In addition, transgenic
      expression of a functional Naip5 allele in A/J macrophages did not alter
      Legionella-induced caspase-1 activation and IL-1beta secretion. Notably,
      defective Naip5 signaling renders B6-Naip5(A/J) macrophages permissive for
      Legionella proliferation despite normal caspase-1 activation. These results
      indicate that the restriction of intracellular Legionella replication is more
      complex than previously appreciated and requires both Ipaf-dependent caspase-1
      activation as well as functional Naip5 signaling.

PMID- 17548640
TI  - IL-10 underlies distinct susceptibility of BALB/c and C57BL/6 mice to
      Mycobacterium avium infection and influences efficacy of antibiotic therapy.
AB  - Increased production of IL-10 has been frequently associated with augmented
      susceptibility to infection. However, the correlation between IL-10 activity and
      susceptibility to mycobacterial infection is still uncertain. Although studies
      using transgenic mice overexpressing IL-10 consistently showed an increased
      susceptibility to mycobacterial infection, experimental approaches in which IL-10
      activity was reduced or abrogated originated inconclusive data. We show here that
      this controversy might be due to the mouse strains used in the various
      experimental procedures. Our results show that BALB/c mice are more susceptible
      than C57BL/6 to Mycobacterium avium infection. This increased susceptibility of
      BALB/c mice is, to a great extent, due to distinct activity of IL-10 between the
      two mouse strains. In accordance, reduction of IL-10 activity through the
      administration of anti-IL-10R mAb, or the absence of IL-10 as studied in IL-10
      knockout mice, clearly decreased the susceptibility of BALB/c mice to M. avium
      but had a less obvious effect in C57BL/6 mice. Moreover, abrogation of IL-10
      activity in infected BALB/c mice increased the efficacy of antimycobacterial
      therapy, whereas for the C57BL/6 mice it produced no effect. These observations
      show that the activity of IL-10 in response to the same mycobacterial stimulus
      influences not only the susceptibility to infection but also the efficacy of
      antimycobacterial therapy. This should now be considered in the context of human
      response to mycobacterial infection, particularly as a possible strategy to
      improve treatment against infections by mycobacteria.

PMID- 17548641
TI  - Leukotriene B4 triggers the in vitro and in vivo release of potent antimicrobial
      agents.
AB  - Leukotriene B(4) (LTB(4)) is a bioactive lipid derived from the metabolism of
      arachidonic acid. Mainly produced by polymorphonuclear leukocytes (PMN) and
      macrophages, LTB(4) triggers several functional responses important in host
      defense, including the secretion of lysosomal enzymes, the activation of NADPH
      oxidase activity, NO formation, and phagocytosis. We report that LTB(4), but not
      structural analogs thereof, stimulates primed human PMN to release molecules
      having potent antimicrobial activities. Exposure of bacteria (Escherichia coli
      and Staphylococcus aureus) or viruses (herpes simplex virus type 1 and HIV type
      1) to supernatants of LTB(4)-activated PMN led to > or =90% reduction in
      infectivity. ELISA and mass spectroscopy analysis of proteins released from
      LTB(4)-activated PMN have identified several antimicrobial proteins, including
      alpha-defensins, cathepsin G, elastase, lysozyme C, and LL-37, that are likely to
      participate in the killing of microorganisms. In addition to these in vitro
      observations, i.v. injections of LTB(4) (50 microg/kg) to monkeys led to an
      increase in alpha-defensin plasmatic levels and enhanced ex vivo antimicrobial
      activities of plasma. These results demonstrate the ability of LTB(4) to cause
      the release of potent antimicrobial agents from PMN in vitro as well as in vivo
      and add further support to the important role of LTB(4) in host defense.

PMID- 17548642
TI  - Human neutrophil defensins increase neutrophil uptake of influenza A virus and
      bacteria and modify virus-induced respiratory burst responses.
AB  - Human neutrophil peptides (HNPs) are released from granules of neutrophils in
      response to various activating stimuli and they participate in the killing of
      bacteria and the stimulation of various inflammatory responses. HNPs also inhibit
      infectivity of enveloped viruses, including influenza A virus (IAV). In this
      study, we demonstrate that HNPs increase the uptake of IAV and bacteria by
      neutrophils. The dimeric HNPs also induced aggregation of IAV and bacterial
      particles, which may, in part, explain their ability to increase uptake. HNPs did
      not increase neutrophil respiratory burst responses to IAV. We have recently
      demonstrated direct interactions of HNPs with surfactant protein D (SP-D),
      another important effector of innate immunity and antimicrobial host defense.
      Although HNPs did not alter SP-D-dependent uptake of IAV, they counteracted the
      ability of SP-D to increase IAV-induced neutrophil H2O2 generation. Our studies
      reveal previously unappreciated functional effects of HNPs, expand our
      understanding of the antiviral properties of HNPs, and suggest important
      interactions between collectins and HNPs in the host response to viruses and
      bacteria.

PMID- 17548643
TI  - Expression and regulation of the metalloproteinase ADAM-8 during human neutrophil
      pathophysiological activation and its catalytic activity on L-selectin shedding.
AB  - A disintegrin and metalloproteinase domain (ADAM) proteins are a family of
      transmembrane glycoproteins with heterogeneous expression profiles and
      proteolytic, cell-adhesion, -fusion, and -signaling properties. One of its
      members, ADAM-8, is expressed by several cell types including neurons,
      osteoclasts, and leukocytes and, although it has been implicated in
      osteoclastogenesis and neurodegenerative processes, little is known about its
      role in immune cells. In this study, we show that ADAM-8 is constitutively
      present both on the cell surface and in intracellular granules of human
      neutrophils. Upon in vitro neutrophil activation, ADAM-8 was mobilized from the
      granules to the plasma membrane, where it was released through a
      metalloproteinase-dependent shedding mechanism. Adhesion of resting neutrophils
      to human endothelial cells also led to up-regulation of ADAM-8 surface
      expression. Neutrophils isolated from the synovial fluid of patients with active
      rheumatoid arthritis expressed higher amounts of ADAM-8 than neutrophils isolated
      from peripheral blood and the concentration of soluble ADAM-8 in synovial fluid
      directly correlated with the degree of joint inflammation. Remarkably, the
      presence of ADAM-8 both on the cell surface and in suspension increased the
      ectodomain shedding of membrane-bound L-selectin in mammalian cells. All these
      data support a potential relevant role for ADAM-8 in the function of neutrophils
      during inflammatory response.

PMID- 17548644
TI  - Regulated shedding of transmembrane chemokines by the disintegrin and
      metalloproteinase 10 facilitates detachment of adherent leukocytes.
AB  - CX3CL1 (fractalkine) and CXCL16 are unique members of the chemokine family
      because they occur not only as soluble, but also as membrane-bound molecules.
      Expressed as type I transmembrane proteins, the ectodomain of both chemokines can
      be proteolytically cleaved from the cell surface, a process known as shedding.
      Our previous studies showed that the disintegrin and metalloproteinase 10
      (ADAM10) mediates the largest proportion of constitutive CX3CL1 and CXCL16
      shedding, but is not involved in the phorbolester-induced release of the soluble
      chemokines (inducible shedding). In this study, we introduce the calcium
      ionophore ionomycin as a novel, very rapid, and efficient inducer of CX3CL1 and
      CXCL16 shedding. By transfection in COS-7 cells and ADAM10-deficient murine
      embryonic fibroblasts combined with the use of selective metalloproteinase
      inhibitors, we demonstrate that the inducible generation of soluble forms of
      these chemokines is dependent on ADAM10 activity. Analysis of the C-terminal
      cleavage fragments remaining in the cell membrane reveals multiple cleavage sites
      used by ADAM10, one of which is preferentially used upon stimulation with
      ionomycin. In adhesion studies with CX3CL1-expressing ECV-304 cells and cytokine
      stimulated endothelial cells, we demonstrate that induced CX3CL1 shedding leads
      to the release of bound monocytic cell lines and PBMC from their cellular
      substrate. These data provide evidence for an inducible release mechanism via
      ADAM10 potentially important for leukocyte diapedesis.

PMID- 17548645
TI  - Long-term commitment to inflammation-seeking homing in CD4+ effector cells.
AB  - Access of T effector cells to sites of inflammation is a prerequisite for an
      efficient action in immune defense and is mediated by different, partly tissue
      specific sets of adhesion molecules. To what extent lymphocytes memorize the site
      of initial priming and develop organ-specific homing properties is still a matter
      of debate. Notably, data on the stability of homing receptor expression on T
      cells in vivo are largely lacking. We approached this question by the adoptive
      transfer of CD4(+) T cells sorted for the expression of P-selectin ligands, which
      contribute to migration into inflamed sites in skin and other tissues. We
      observed long-term expression of P-selectin ligands on roughly one-third of
      effector cells. On those cells that had lost P-selectin ligands, re-expression
      upon Ag challenge was observed but only within pLNs, similar to the organ
      selective induction upon the primary activation of naive T cells. The frequency
      of cells stably expressing P-selectin ligands was higher when cells were
      repeatedly stimulated under permissive conditions in the presence of IL-12,
      indicating a gradual fixation of this phenotype. In line with that finding,
      isolated P-selectin ligand positive memory T cells showed the highest frequency
      of long-term expressing cells. A tissue-specific environment was not required for
      the long-term maintenance of P-selectin ligand expression on the subfraction of
      effector cells. These data indicate that the expression of selectin ligands can
      become clonally imprinted under certain conditions, but also that a major
      fraction of the cells remains flexible and subject to environmental modulation
      upon restimulation.

PMID- 17548646
TI  - Histamine 4 receptor activation induces recruitment of FoxP3+ T cells and
      inhibits allergic asthma in a murine model.
AB  - Histamine has an important role in regulation of immune response which is
      mediated by differential expression of four distinct receptors, H1R-H4R. H1R and
      HR2 have previously been shown to be involved with modulation of lung
      inflammation. H4R is also expressed on inflammatory cells; therefore, we
      investigated the potential role of H4R in development of allergic asthma in a
      murine model. We determined that the H4R agonist 4-methylhistamine when delivered
      intratracheally before Ag challenge mitigated airway hyperreactivity and
      inflammation. This was associated with an increase in IL-10 and IFN-gamma, but
      not TGF-beta or IL-16, as well as a decrease in IL-13 in the bronchoalveolar
      lavage fluid. We also observed that H4R agonist instillation resulted in
      accumulation of FoxP3(+) T cells suggesting a direct effect on T regulatory cell
      recruitment. To investigate this further, we determined the in vitro effect of
      H4R stimulation on human T cell migration. The H4R agonist induced a 2- to 3-fold
      increase in T cell migration, similar to that seen for H1R agonists. Cells
      transmigrating to the H4R agonist, but not H1R, were skewed toward a CD4 cell
      expressing CD25 and intracellular FoxP3. H4R-responsive cells suppressed
      proliferation of autologous T cells, an effect that was dependent on IL-10
      production. We conclude that H4R stimulation enriches for a regulatory T cell
      with potent suppressive activity for proliferation. These findings identify a
      novel function for H4R and suggest a potential therapeutic approach to
      attenuation of asthmatic inflammation.

PMID- 17548647
TI  - CD8+ T Cells are required for inflammation and destruction in cigarette smoke
      induced emphysema in mice.
AB  - Increased numbers of T lymphocytes are observed in the lungs of patients with
      chronic obstructive pulmonary disease, but their role in the disease process is
      not known. We investigated the role of CD8+ T cells in inflammatory cell
      recruitment and lung destruction in a cigarette smoke-induced murine model of
      emphysema. In contrast to wild-type C57BL/6J mice that displayed macrophage,
      lymphocyte, and neutrophil recruitment to the lung followed by emphysema in
      response to cigarette smoke, CD8+ T cell-deficient (CD8-/-) mice had a blunted
      inflammatory response and did not develop emphysema when exposed to long-term
      cigarette smoke. Further studies supported a pathogenetic pathway whereby the
      CD8+ T cell product, IFN-gamma-inducible protein-10, induces production of
      macrophage elastase (matrix metalloproteinase 12) that degrades elastin, both
      causing lung destruction directly and generating elastin fragments that serve as
      monocyte chemokines augmenting macrophage-mediated lung destruction. These
      studies demonstrate a requirement for CD8+ T cells for the development of
      cigarette smoke-induced emphysema and they provide a unifying pathway whereby
      CD8+ T cells are a central regulator of the inflammatory network in chronic
      obstructive pulmonary disease.

PMID- 17548648
TI  - Monocyte chemoattractant protein-1 production by intestinal myofibroblasts in
      response to staphylococcal enterotoxin a: relevance to staphylococcal
      enterotoxigenic disease.
AB  - Food poisoning due to staphylococcal enterotoxins A and B (SEA and SEB) affects
      hundreds of thousands of people annually. SEA and SEB induce massive intestinal
      cytokine production, which is believed to be the key factor in staphylococcal
      enterotoxin enteropathy. MHC class II molecules are the major receptors for
      staphylococcal enterotoxins. We recently demonstrated that normal human
      subepithelial intestinal myofibroblasts (IMFs) express MHC class II molecules. We
      hypothesized that IMFs are among the first cells to respond to staphylococcal
      enterotoxins and contribute to the cytokine production associated with
      staphylococcal enterotoxin pathogenesis. We demonstrated here that primary
      cultured IMFs bind staphylococcal enterotoxins in a MHC class II-dependent
      fashion in vitro. We also demonstrated that staphylococcal enterotoxins can cross
      a CaCo-2 epithelial monolayer in coculture with IMFs and bind to the MHC class II
      on IMFs. IMFs responded to SEA, but not SEB, exposure with 3- to 20-fold
      increases in the production of proinflammatory chemokines (MCP-1, IL-8),
      cytokines (IL-6), and growth factors (GM-CSF and G-CSF). The SEA induction of the
      proinflammatory mediators by IMFs resulted from the efficient cross-linking of
      MHC class II molecules because cross-linking of class II MHC by biotinylated anti
      HLA-DR Abs induced similar cytokine patterns. The studies presented here show
      that MCP-1 is central to the production of other cytokines elicited by SEA in
      IMFs because its neutralization with specific Abs prevented the expression of IL
      6 and IL-8 by IMFs. Thus, MCP-1 may play a leading role in initiation of
      inflammatory injury associated with staphylococcal enterotoxigenic disease.

PMID- 17548649
TI  - STAT1 activation causes translocation of Bax to the endoplasmic reticulum during
      the resolution of airway mucous cell hyperplasia by IFN-gamma.
AB  - Disruption of the normal resolution process of inflammation-induced mucous cell
      hyperplasia may lead to sustained mucous hypersecretion in chronic diseases.
      During prolonged exposure of mice to allergen, IFN-gamma reduces mucous cell
      hyperplasia, but the signaling responsible for the cell death is largely unknown.
      A brief phosphorylation of STAT1 by IFN-gamma was required for cell death in
      airway epithelial cells (AEC), and during prolonged exposure to allergen, mucous
      cell hyperplasia remained elevated in STAT1(-/-) but was resolved in STAT1(+/+)
      mice. Although IFN-gamma treatment of primary human AECs and other airway cell
      lines left Bax protein levels unchanged, it caused translocation of Bax from the
      cytosol to the endoplasmic reticulum (ER) but not to the mitochondria.
      Localization of Bax to the ER was observed in IFN-gamma-treated primary AECs
      isolated from STAT1(+/+) mice but not in cells from STAT1(-/-) mice. In addition,
      ER Bax was detected in mucous cells of STAT1(+/+) but not STAT1(-/-) airways of
      mice exposed to allergen for prolonged periods. IFN-gamma did not release
      cytochrome c from mitochondria but reduced ER calcium stores and dilated the ER,
      confirming that the IFN-gamma-induced cell death is mediated through changes
      localized in the ER. Collectively, these observations suggest that STAT1
      dependent translocation of Bax to the ER is crucial for IFN-gamma-induced cell
      death of AECs and the resolution of allergen-induced mucous cell hyperplasia.

PMID- 17548650
TI  - TNF-alpha inhibits macrophage clearance of apoptotic cells via cytosolic
      phospholipase A2 and oxidant-dependent mechanisms.
AB  - Removal of apoptotic cells from inflammatory sites is an important step in the
      resolution of inflammation. Both murine and human macrophages stimulated with TNF
      alpha or directly administered arachidonic acid showed an impaired ability to
      ingest apoptotic cells (efferocytosis). The inhibition was shown to be due to
      generation of reactive oxygen species, was blocked with a superoxide dismutase
      mimetic, MnTBAP, and was mimicked by direct addition of H2O2. To determine the
      mechanism of TNF-alpha-stimulated oxidant production, bone marrow-derived
      macrophages from gp91(phox)-deficient mice were examined but shown to still
      produce oxidants and exhibit defective apoptotic cell uptake. In contrast, a
      specific cytosolic phospholipase A2 inhibitor blocked the oxidant production and
      reversed the inhibited uptake. The suppressive effect of endogenous or exogenous
      oxidants on efferocytosis was mediated through activation of the GTPase, Rho. It
      was reversed in macrophages pretreated with C3 transferase to inactivate Rho or
      with an inhibitor of Rho kinase. During maturation of human monocyte-derived
      macrophages, only mature cells exhibited TNF-alpha-induced suppression of
      apoptotic cell clearance. The resistance of immature macrophages to such
      inhibition was shown to result not from defective generation of oxidants, but
      rather, from lack of response of these cells to the oxidants. Overall, the data
      suggest that macrophages in a TNF-alpha- and oxidant-rich inflammatory
      environment are less able to remove apoptotic cells and, thereby, may contribute
      to the local intensity of the inflammatory response.

PMID- 17548651
TI  - Identification of ectonucleotidases CD39 and CD73 in innate protection during
      acute lung injury.
AB  - Acute lung injury (ALI), such as that which occurs with mechanical ventilation,
      contributes to morbidity and mortality of critical illness. Nonetheless, in many
      instances, ALI resolves spontaneously through unknown mechanisms. Therefore, we
      hypothesized the presence of innate adaptive pathways to protect the lungs during
      mechanical ventilation. In this study, we used ventilator-induced lung injury as
      a model to identify endogenous mechanisms of lung protection. Initial in vitro
      studies revealed that supernatants from stretch-induced injury contained a stable
      factor which diminished endothelial leakage. This factor was subsequently
      identified as adenosine. Additional studies in vivo revealed prominent increases
      in pulmonary adenosine levels with mechanical ventilation. Because ectoapyrase
      (CD39) and ecto-5'-nucleotidase (CD73) are rate limiting for extracellular
      adenosine generation, we examined their contribution to ALI. In fact, both
      pulmonary CD39 and CD73 are induced by mechanical ventilation. Moreover, we
      observed pressure- and time-dependent increases in pulmonary edema and
      inflammation in ventilated cd39(-/-) mice. Similarly, pharmacological inhibition
      or targeted gene deletion of cd73 was associated with increased symptom severity
      of ventilator-induced ALI. Reconstitution of cd39(-/-) or cd73(-/-) mice with
      soluble apyrase or 5'-nucleotidase, respectively, reversed such increases. In
      addition, ALI was significantly attenuated and survival improved after i.p.
      treatment of wild-type mice with soluble apyrase or 5'-nucleotidase. Taken
      together, these data reveal a previously unrecognized role for CD39 and CD73 in
      lung protection and suggest treatment with their soluble compounds as a
      therapeutic strategy for noninfectious ALI.

PMID- 17548652
TI  - The proinflammatory effect of prostaglandin E2 in experimental inflammatory bowel
      disease is mediated through the IL-23-->IL-17 axis.
AB  - Although Crohn's disease has been traditionally considered to be Th1-mediated,
      the newly identified Th17 cells emerged recently as crucial participants.
      Th1/Th17 differentiation is controlled primarily by the IL-12 family of cytokines
      secreted by activated dendritic cells (DCs) and macrophages. IL-23 and IL-12/IL
      27 have opposite effects, supporting the Th17 and Th1 phenotypes, respectively.
      We found that PGE(2), a major lipid mediator released in inflammatory conditions,
      shifts the IL-12/IL-23 balance in DCs in favor of IL-23, and propose that high
      levels of PGE(2) exacerbate the inflammatory process in inflammatory bowel
      disease through the IL-23-->IL-17 axis. We assessed the effects of PGE(2) on IL
      12, IL-27, and IL-23 and found that PGE(2) promotes IL-23, inhibits IL-12 and IL
      27 expression and release from stimulated DCs, and subsequently induces IL-17
      production in activated T cells. The effects of PGE(2) are mediated through the
      EP2/EP4 receptors on DCs. In vivo, we assessed the effects of PGE analogs in an
      experimental model for inflammatory bowel disease and found that the exacerbation
      of clinical symptoms and histopathology correlated with an increase in IL-23 and
      IL-17, a decrease in IL-12p35 expression in colon and mesenteric lymph nodes, and
      a substantial increase in the number of infiltrating neutrophils and of CD4(+)IL
      17(+) T cells in the colonic tissue. These studies suggest that high levels of
      PGE(2) exacerbate the inflammatory process through the preferential expression
      and release of DC-derived IL-23 and the subsequent support of the
      autoreactive/inflammatory Th17 phenotype.

PMID- 17548653
TI  - Pulmonary stromal-derived factor-1 expression and effect on neutrophil
      recruitment during acute lung injury.
AB  - The severe and protracted inflammation that characterizes acute lung injury (ALI)
      is driven by the ongoing recruitment of neutrophils to the lung. Although much of
      the cytokine signaling responsible for the initial phase of ALI has been
      elaborated, relatively little is known about the mechanisms governing the
      recruitment of neutrophils from the bone marrow to the lung in the later period
      of this disease. Given its previously described chemoattractant effects on marrow
      neutrophils, we investigated whether stromal-derived factor-1 (SDF-1) (CXCL12)
      might participate in this later phase of recruitment. Using immunohistochemistry
      to examine both banked human lung specimens from patients with ALI and lungs from
      mice with LPS-induced pneumonitis, we found that pulmonary SDF-1 expression
      increases during ALI. We further determined that both lung SDF-1 protein
      expression and mRNA expression rise in a delayed but sustained pattern in this
      mouse model and that the major source of the increase in expression appears to be
      the lung epithelium. Lastly, we found that expression of the SDF-1 receptor CXCR4
      rises in a similar temporal pattern on neutrophils in both the blood and airspace
      of LPS-injured mice and that Ab-mediated SDF-1 blockade significantly attenuates
      late but not early pulmonary neutrophilia in this model. These results implicate
      SDF-1 in neutrophil recruitment to the lung in the later period of acute lung
      injury and suggest a novel role for this cytokine in coordinating the transition
      from the inflammatory response to the initiation of tissue repair.

PMID- 17548654
TI  - Fibronectin- and vitronectin-induced microglial activation and matrix
      metalloproteinase-9 expression is mediated by integrins alpha5beta1 and
      alphavbeta5.
AB  - Early in the pathogenesis of multiple sclerosis, the blood-brain barrier is
      compromised, which leads to deposition of the plasma proteins fibronectin and
      vitronectin in cerebral parenchyma. In light of our previous finding that
      microglial activation in vitro is strongly promoted by fibronectin and
      vitronectin, we set out to examine the possibility that modulation of microglial
      activation by fibronectin or vitronectin is an important regulatory mechanism in
      vivo. In an experimental autoimmune encephalomyelitis mouse model of
      demyelination, total brain levels of fibronectin and vitronectin were strongly
      increased and there was a close relationship between fibronectin and vitronectin
      deposition, microglial activation, and microglial expression of matrix
      metalloproteinase-9. In murine cell culture, flow cytometry for MHC class I and
      gelatin zymography revealed that microglial activation and expression of pro
      matrix metalloproteinase-9 were significantly increased by fibronectin and
      vitronectin. Function-blocking studies showed that the influence of fibronectin
      and vitronectin was mediated by the alpha(5)beta(1) and alpha(v)beta(5)
      integrins, respectively. Taken together, this work suggests that fibronectin and
      vitronectin deposition during demyelinating disease is an important influence on
      microglial activation state. Furthermore, it provides the first evidence that the
      alpha(5)beta(1) and alpha(v)beta(5) integrins are important mediators of
      microglial activation.

PMID- 17548655
TI  - Shiga toxin produced by enterohemorrhagic Escherichia coli inhibits PI3K/NF
      kappaB signaling pathway in globotriaosylceramide-3-negative human intestinal
      epithelial cells.
AB  - Shiga toxin (Stx) produced by enterohemorrhagic Escherichia coli (EHEC) binds to
      endothelial cells expressing globotriaosylceramide-3 (Gb-3) and induces cell
      death by inhibiting translation. Nonetheless, the effects of Stx on human
      enterocytes, which lacks receptor Gb-3, remain less known. In this study, we
      questioned whether EHEC-derived Stx may modulate cellular signalization in the Gb
      3-negative human epithelial cell line T84. Stx produced by EHEC was fixed and
      internalized by the cells. A weak activation of NF-kappaB was observed in T84
      cells after EHEC infection. Cells infected with an isogenic mutant lacking stx1
      and stx2, the genes encoding Stx, displayed an increased NF-kappaB DNA-binding
      activity. Consequently, the NF-kappaB-dependent CCL20 and IL-8 gene transcription
      and chemokine production were enhanced in T84 cells infected with the Stx mutant
      in comparison to the wild-type strain. Investigating the mechanism by which Stx
      modulates NF-kappaB activation, we showed that the PI3K/Akt signaling pathway was
      not induced by EHEC but was enhanced by the strain lacking Stx. Pharmacological
      inhibition of the PI3K/Akt signalization in EHEC DeltaStx-infected T84 cells
      yielded to a complete decrease of NF-kappaB activation and CCL20 and IL-8 mRNA
      expression. This demonstrates that the induction of the PI3K/Akt/NF-kappaB
      pathway is potentially induced by EHEC, but is inhibited by Stx in Gb-3-negative
      epithelial cells. Thus, Stx is an unrecognized modulator of the innate immune
      response of human enterocytes.

PMID- 17548656
TI  - IFN-gamma-induced chemokines synergize with pertussis toxin to promote T cell
      entry to the central nervous system.
AB  - Inflammation of the CNS, which occurs during multiple sclerosis and experimental
      autoimmune encephalomyelitis, is characterized by increased levels of IFN-gamma,
      a cytokine not normally expressed in the CNS. To investigate the role of IFN
      gamma in CNS, we used intrathecal injection of a replication-defective adenovirus
      encoding murine IFN-gamma (AdIFNgamma) to IFN-gamma-deficient (GKO) mice. This
      method resulted in stable, long-lived expression of IFN-gamma that could be
      detected in cerebrospinal fluid using ELISA and Luminex bead immunoassay. IFN
      gamma induced expression in the CNS of message and protein for the chemokines
      CXCL10 and CCL5, to levels comparable to those seen during experimental
      autoimmune encephalomyelitis. Other chemokines (CXCL2, CCL2, CCL3) were not
      induced. Mice lacking the IFN-gammaR showed no response, and a control viral
      vector did not induce chemokine expression. Chemokine expression was
      predominantly localized to meningeal and ependymal cells, and was also seen in
      astrocytes and microglia. IFN-gamma-induced chemokine expression did not lead to
      inflammation. However, when pertussis toxin was given i.p. to mice infected with
      the IFN-gamma vector, there was a dramatic increase in the number of T
      lymphocytes detected in the CNS by flow cytometry. This increase in blood-derived
      immune cells in the CNS did not occur with pertussis toxin alone, and did not
      manifest as histologically detectable inflammatory pathology. These results show
      that IFN-gamma induces a characteristic glial chemokine response that by itself
      is insufficient to promote inflammation, and that IFN-gamma-induced CNS
      chemoattractant signals can synergize with a peripheral infectious stimulus to
      drive T cell entry into the CNS.

PMID- 17548657
TI  - A previously unrecognized protein-protein interaction between TWEAK and CD163:
      potential biological implications.
AB  - TWEAK (TNF-like weak inducer of apoptosis) is a TNF superfamily member implicated
      in several mechanisms. Although fibroblast growth factor inducible 14
      (Fn14)/TweakR has been reported as its receptor, an as yet unrecognized surface
      molecule(s) might modulate TWEAK function(s). Thus, we set out to identify TWEAK
      binding proteins by screening a combinatorial peptide library. Cyclic peptides
      containing a consensus motif (WXDDG) bound to TWEAK specifically. These peptides
      were similar to CD163, a scavenger receptor cysteine-rich domain family member,
      restricted to the monocyte/macrophage lineage and responsible for the uptake of
      circulating haptoglobin-hemoglobin (Hp-Hb) complexes. Sequence profile analysis
      suggested that TWEAK mimicked the CD163 natural ligand (Hp-Hb). Consistently, we
      show dose-dependent TWEAK binding to CD163 and blockade by an anti-CD163 Ab. In a
      competition assay, both soluble CD163 and Fn14/TweakR were able to compete off
      TWEAK binding to coated Fn14/TweakR or CD163, respectively. Flow-cytometry and
      immunofluorescence assays showed that human monocytes (Fn14/TweakR negative and
      CD163 positive) bind TWEAK, thus blocking the recognition of CD163 and reducing
      the activation mediated by a specific mAb in these cells. We demonstrate that
      monocytes can sequester TWEAK from supernatants, thus preventing tumor cell
      apoptosis; this effect was reverted by preincubation with the peptide mimicking
      CD163 or with a mAb anti-CD163, indicating specificity. Finally, we show that
      recombinant human TWEAK binding to CD163-transfected Chinese hamster ovary cells
      is inhibited by the presence of either unlabeled TWEAK or the Hp-Hb complex.
      Together, these data are consistent with the hypothesis that CD163 either acts as
      a TWEAK scavenger in pathological conditions or serves as an alternate receptor
      for TWEAK in cells lacking Fn14/TweakR.

PMID- 17548658
TI  - Characterization of reciprocal Lmb1-4 interval MRL-Faslpr and C57BL/6-Faslpr
      congenic mice reveals significant effects from Lmb3.
AB  - Susceptibility to severe lupus in MRL-Fas(lpr) mice requires not only the lpr
      mutation but also other predisposing genes. Using (MRL-Fas(lpr) x B6-Fas(lpr))F2
      (where B6 represents C57BL/6) intercrosses that utilize the highly susceptible
      MRL and poorly susceptible B6 backgrounds, we previously mapped CFA-enhanced
      systemic lupus-like autoimmunity to four loci, named Lmb1-4, on chromosomes 4, 5,
      7, and 10. In the current study, we generated and analyzed reciprocal interval
      congenic mice for susceptibility to CFA-enhanced autoimmunity at all four Lmb
      loci. Although all loci had at least a slight effect on lymphoproliferation, only
      Lmb3 demonstrated a major effect on lymphoproliferation and anti-chromatin Ab
      levels. Further characterization of Lmb3, primarily by comparing MRL-Fas(lpr)
      with MRL.B6-Lmb3 Fas(lpr) congenic mice, revealed that it also played a
      significant role in spontaneous lupus, modifying lymphoproliferation, IgG and
      autoantibody levels, kidney disease, and survival. The less susceptible B6 Lmb3
      locus was associated with a marked reduction in numbers of CD4(+) and double
      negative (CD4(-)CD8(-)) T cells, particularly in lymph nodes, as well as reduced
      T cell proliferation and enhanced T cell apoptosis, both in vivo and in vitro.
      IFN-gamma-producing CD4(+) T cells were also reduced in MRL.B6-Lmb3 Fas(lpr)
      mice. Further mapping using subinterval congenic mice placed Lmb3 in the
      telomeric portion of chromosome 7. Thus, Lmb3, primarily through its effects on
      CD4(+) and double-negative T cells, appears to be a highly penetrant lupus
      modifying locus. Identification of the underlying genetic alteration responsible
      for this quantitative trait locus should provide new insights into lupus
      modifying genes.

PMID- 17548659
TI  - Regulation of DMBT1 via NOD2 and TLR4 in intestinal epithelial cells modulates
      bacterial recognition and invasion.
AB  - Mucosal epithelial cell layers are constantly exposed to a complex resident
      microflora. Deleted in malignant brain tumors 1 (DMBT1) belongs to the group of
      secreted scavenger receptor cysteine-rich proteins and is considered to be
      involved in host defense by pathogen binding. This report describes the
      regulation and function of DMBT1 in intestinal epithelial cells, which form the
      primary immunological barrier for invading pathogens. We report that intestinal
      epithelial cells up-regulate DMBT1 upon proinflammatory stimuli (e.g., TNF-alpha,
      LPS). We demonstrate that DMBT1 is a target gene for the intracellular pathogen
      receptor NOD2 via NF-kappaB activation. DMBT1 is strongly up-regulated in the
      inflamed intestinal mucosa of Crohn's disease patients with wild-type, but not
      with mutant NOD2. We show that DMBT1 inhibits cytoinvasion of Salmonella enterica
      and LPS- and muramyl dipeptide-induced NF-kappaB activation and cytokine
      secretion in vitro. Thus, DMBT1 may play an important role in the first line of
      mucosal defense conferring immune exclusion of bacterial cell wall components.
      Dysregulated intestinal DMBT1 expression due to mutations in the NOD2/CARD15 gene
      may be part of the complex pathophysiology of barrier dysfunction in Crohn's
      disease.

PMID- 17548660
TI  - Loss of discrete memory B cell subsets is associated with impaired immunization
      responses in HIV-1 infection and may be a risk factor for invasive pneumococcal
      disease.
AB  - Invasive pneumococcal infection is an important cause of morbidity and mortality
      in HIV-1-infected individuals. B cells play an important role in maintaining
      serologic memory after infection. IgM memory B cells are significantly reduced in
      HIV-1-infected patients and their frequency is similar to that observed in other
      patient groups (splenectomized individuals and patients with primary Ab
      deficiency) who are also known to have an increased risk of invasive pneumococcal
      infection. Antiretroviral therapy does not restore marginal zone B cell
      percentages. Immunization with the 23-valent polysaccharide pneumococcal vaccine
      shows that HIV-1-infected patients have impaired total IgM and IgG pneumococcal
      vaccines compared with healthy controls. Loss of switched memory B cells was
      associated with impaired tetanus toxoid IgG vaccine responses. Results of this
      study demonstrate that defects in B cell memory subsets are associated with
      impaired humoral immune responses in HIV-1 patients who are receiving
      antiretroviral therapy and may be a contributory factor to the increased risk of
      invasive pneumococcal infection observed in HIV-1 infection.

PMID- 17548661
TI  - Why smoking prevention programs sometimes fail. Does effectiveness depend on
      sociocultural context and individual characteristics?
AB  - BACKGROUND: School-based smoking prevention programs sometimes fail in unexpected
      ways. This study tests the hypotheses that both social/cultural contexts and
      individual dispositional characteristics may interact with program content to
      produce effects that are variable in potentially predictable ways. METHODS:
      Students in 24 culturally heterogeneous or primarily Hispanic/Latino middle
      schools (N = 3,157 6th graders) received a multicultural collectivist-framed
      social influences (SI) program, an individualist-framed SI program, or a control
      condition. Three-way linear and nonlinear interactions, program frame x social
      context x dispositional phenotype, were tested. RESULTS: Three-way interactions
      were found for the dispositional phenotypes of depression and hostility with
      social context and program content/frame. In predominantly Hispanic/Latino
      schools, larger program effects were observed for high depressed and high hostile
      youth in both the collectivist and individualist framed programs. In culturally
      mixed schools, prevention effects were greatest for low depressed and low hostile
      youth, especially in the individualist framed program. In culturally mixed
      schools, there may have been a negative treatment effect for both programs among
      adolescents scoring high on depression and hostility. DISCUSSION: Prevention
      program effects can vary by combination of program content, social setting, and
      individual dispositional characteristics. The results suggest that prevention
      program design and implementation should be sensitive to population
      characteristics at both the individual and sociocultural levels.

PMID- 17548662
TI  - Intermediate outcomes from Project MYTRI: mobilizing youth for tobacco-related
      initiatives in India.
AB  - The purpose of this article is to present the intermediate results for Project
      MYTRI, a school-based, multiple component intervention designed to prevent and
      reduce many forms of tobacco use (chewing tobacco, cigarettes, and bidis) among
      youth in India. The intervention is based on effective models in the United
      States "translated" for use in this context. The intervention targets two cohorts
      of students who were in the 6th and 8th grade when the study started. Thirty-two
      schools in Delhi (north India) and Chennai (south India) were randomized to
      receive the intervention (n = 16) or serve as a delayed intervention control (n =
      16). Students in these schools were surveyed before the intervention began and at
      an intermediate point, 1 year into this 2-year intervention (n = 8,369). A test
      of the changes in risk factors for tobacco use between the baseline and
      intermediate surveys revealed that, compared with the control, students in the
      intervention condition (a) had better knowledge about the health effects of
      tobacco (P < 0.01); (b) believed that there were more negative social
      consequences to using tobacco (P = 0.04); (c) had fewer reasons to use tobacco (P
      < 0.01); (d) had more reasons not to use tobacco (P = 0.03); (e) were less
      socially susceptible to chewing (P = 0.04) and smoking (P = 0.03) tobacco; (f)
      perceived fewer peers and adults around them smoked (P < 0.01) or chewed (P <
      0.01) tobacco; (g) felt that tobacco use was not acceptable, especially among
      their peers (P < 0.01); (h) were more confident in their ability to advocate for
      tobacco control (P = 0.03); (i) were more knowledgeable about tobacco control
      policies (P < 0.01); and (j) supported these policies, too (P = 0.04). Fewer
      students in the intervention condition reported having intentions to smoke
      tobacco in the next year (P = 0.02) or chew tobacco when they reached college (P
      < 0.01). No changes in actual tobacco use were observed at this stage of the
      study.

PMID- 17548663
TI  - Genetic and environmental sources of variation in heart rate response to infused
      nicotine in twins.
AB  - The heart rate response to nicotine may be an important component of the process
      leading to dependence. The present study is the first to determine the extent to
      which genetic and environmental sources play a role in various components of the
      heart rate response. One hundred and ten monozygotic and 29 dizygotic twin pairs
      received an i.v. infusion of nicotine and cotinine over 30 min. Before, during,
      and for 30 min after infusion, heart rate was measured via an electronic monitor.
      The clearance of nicotine was determined as a measure of the rate of nicotine
      metabolism. Average resting heart rate before infusion was 64.7 beats per minutes
      (bpm), and at the termination of infusion, heart rate had increased to an average
      of 72.7 bpm. At 30 min after infusion, heart rate had decreased to 67.5 bpm. Age,
      current smoking status, body mass index, and nicotine clearance were associated
      significantly with heart rate levels over the full 60 min of measurement. After
      adjustment for several covariates, including dose of administered nicotine and
      rate of nicotine clearance, the variance in several characteristics of the heart
      rate response curve was examined for the relative contribution from genetic and
      environmental sources. In the total sample, as much as 30.3% of the variance in
      the acceleration of heart rate was due to additive genetic sources. In
      nonsmokers, 34.8% and 31.0% of variance in the acceleration and deceleration of
      heart rate, respectively, was due to genetic sources. Heart rate acceleration and
      deceleration may be a reflection of central nervous system responsiveness to
      nicotine. The contribution from genetic sources to heart rate response
      characteristics should be investigated further as a potential endophenotype for
      use in genetic studies of nicotine dependence.

PMID- 17548665
TI  - The cigarette controversy.
AB  - This study examines the history of the cigarette controversy using the tobacco
      documents as a roadmap to explore the following four questions: (a) What did
      tobacco companies know about the health risks of smoking and when did they know
      it? (b) What evidence is there that tobacco companies conspired to deliberately
      mislead the public about the health risks of smoking? (c) How were scientists
      involved in the cigarette controversy? (d) Have tobacco companies changed the way
      they do business since signing the 1998 Master Settlement Agreement? The tobacco
      companies knew and for most part accepted the evidence that cigarette smoking was
      a cause of cancer by the late 1950s. The documents also reveal that the tobacco
      companies helped manufacture the smoking controversy by funding scientific
      research that was intended to obfuscate and prolong the debate about smoking and
      health. Today, the tobacco companies acknowledge that smoking is a cause of
      disease, but they have not materially altered the way they do business. In our
      opinion, it is not sufficient for the tobacco industry to merely concede the
      obvious point that smoking is a cause of disease when it is evident that decades
      of misinformation has resulted in a public that is massively ignorant about the
      risks of smoking low-tar cigarettes, nicotine addiction, and secondhand smoke
      exposure. Public education efforts are still needed to correct these
      misperceptions along with government oversight to ensure that the industry is not
      permitted to mislead the public further. If the past 50 years have taught us
      anything, it is that the tobacco industry cannot be trusted to put the public's
      interest above their profits no matter what they say.

PMID- 17548664
TI  - Association of COMT Val108/158Met genotype with smoking cessation in a nicotine
      replacement therapy randomized trial.
AB  - We investigated the association of catechol O-methyltransferase (COMT) genotype
      with abstinence following a smoking cessation attempt among a large cohort of
      smokers who attempted to quit using either the nicotine transdermal patch or
      placebo and were followed up over an 8-year period following their initial
      cessation attempt. In addition, we examined the possible moderating influence of
      sex on any association. The genotype x treatment interaction effect at 12-week
      follow-up indicated a greater benefit of active nicotine replacement treatment
      compared with placebo on likelihood of abstinence in the COMT Met/Met genotype
      group (33% versus 12%), in comparison to the Met/Val + Val/Val group (22% versus
      16%). Our results indicate that COMT genotype may moderate the effect of active
      transdermal nicotine patch compared with placebo, with reduced relative benefit
      of nicotine replacement therapy in individuals with Met/Val or Val/Val genotype.
      Our data follow an emerging pattern of results suggesting that genetic variation
      in the dopamine pathway may provide a future basis for tailored smoking cessation
      therapies, but indicate that different genes influencing various components of
      this pathway may have different effects on response to smoking cessation
      pharmacotherapy.

PMID- 17548666
TI  - The future of tobacco-control research.
AB  - Recent epidemiologic data on the stabilization of adult and youth smoking rates
      underscore the need for vigorous research across the cancer control spectrum on
      tobacco use interventions. The steady decline in adult rates of smoking has
      stalled for the first time in 8 years, and certain race, ethnic, and population
      groups are disproportionately at risk to tobacco-related cancers because of
      disparities in tobacco use or access to effective interventions. Although
      substantial progress has been made across levels of basic through applied
      research, tobacco-control research across the discovery and delivery continuum
      must be accelerated to further reduce the cancer burden. Following a brief review
      of the prevalence and trends affecting tobacco use initiation and cessation, we
      identify and describe four domains of extraordinary research opportunities:
      genetics and gene-environment interactions, bioinformatics and health
      informatics, disparities and disproportionate risk, and prevention and treatment.
      Evolutionary scientific changes, like rapidly advancing technology and emphasis
      on the paradigm of team science research approaches, provide both a challenge as
      well as unparalleled opportunities for scientific advancement and public health
      progress.

PMID- 17548667
TI  - Parkinson's disease and cancer.

PMID- 17548668
TI  - Heightened risk of breast cancer following pregnancy: could lasting systemic
      immune alterations contribute?
AB  - The protective effect of having a first full-term pregnancy (FFTP) at a younger
      age on women's lifetime risk of breast cancer is well known. Less appreciated is
      the increased risk seen in the years immediately following pregnancy. This
      adverse effect is more pronounced and more prolonged in women with later age at
      FFTP. The mechanisms responsible for this increased risk are still poorly
      understood. In the present paper, we put forward the hypothesis that the marked
      peripheral immune changes induced by pregnancy may account for these effects. We
      highlight immune changes that characterize the unique immune state of pregnancy
      (a combination of cellular immunosuppression and enhanced inflammatory response),
      note the resemblance of these changes to cancer escape mechanisms, and discuss
      why such immune changes may be critical for the development of breast cancer
      following pregnancy. We further support this idea by initial findings from our
      own laboratory that the age at FFTP is negatively related to natural killer cell
      cytotoxicity many years later and propose possible models for the kinetics of the
      immune changes during and following pregnancy. The effect of age at FFTP on the
      immune function is currently understudied. Its potential relevance to the
      development of breast cancer stresses the need for further research.

PMID- 17548669
TI  - The role of osteopontin in tumor progression and metastasis in breast cancer.
AB  - The use of cancer biomarkers to anticipate the outlines of disease has been an
      emerging issue, especially as cancer treatment has made such positive steps in
      the last few years. Progress in the development of consistent malignancy markers
      is imminent because advances in genomics and bioinformatics have allowed the
      examination of immense amounts of data. Osteopontin is a phosphorylated
      glycoprotein secreted by activated macrophages, leukocytes, and activated T
      lymphocytes, and is present in extracellular fluids, at sites of inflammation,
      and in the extracellular matrix of mineralized tissues. Several physiologic roles
      have been attributed to osteopontin, i.e., in inflammation and immune function,
      in mineralized tissues, in vascular tissue, and in kidney. Osteopontin interacts
      with a variety of cell surface receptors, including several integrins and CD44.
      Binding of osteopontin to these cell surface receptors stimulates cell adhesion,
      migration, and specific signaling functions. Overexpression of osteopontin has
      been found in a variety of cancers, including breast cancer, lung cancer,
      colorectal cancer, stomach cancer, ovarian cancer, and melanoma. Moreover,
      osteopontin is present in elevated levels in the blood and plasma of some
      patients with metastatic cancers. Therefore, suppression of the action of
      osteopontin may confer significant therapeutic activity, and several strategies
      for bringing about this suppression have been identified. This review looks at
      the recent advances in understanding the possible mechanisms by which osteopontin
      may contribute functionally to malignancy, particularly in breast cancer.
      Furthermore, the measurement of osteopontin in the blood or tumors of patients
      with cancer, as a way of providing valuable prognostic information, will be
      discussed based on emerging clinical data.

PMID- 17548670
TI  - Genetic variation in H2AFX contributes to risk of non-Hodgkin lymphoma.
AB  - Non-Hodgkin lymphoma (NHL) comprises a group of lymphoid tumors that have in
      common somatic translocations. H2AFX encodes a key histone involved in the
      detection of the DNA double-stranded breaks that can lead to translocations.
      H2afx is a dosage-dependent gene that protects against B-cell lymphomas in mice,
      making its human orthologue an ideal candidate gene for susceptibility to
      lymphoma. We did a population-based genetic association study of H2AFX variants
      in 487 NHL cases and 531 controls. Complete resequencing of the human H2AFX gene
      in 95 NHL cases was done to establish the spectrum of variation in affected
      individuals; this was followed by both direct and indirect tests for association
      at the level of individual single nucleotide polymorphisms (SNP) and as
      haplotypes. Homozygosity for the AA genotype of a SNP 417 bp upstream of the
      translational start of H2AFX is strongly associated [odds ratio (OR), 0.54; P =
      0.001] with protection from NHL. We find a strong association of this SNP with
      the follicular lymphoma subtype of NHL (AA genotype: OR, 0.40; P = 0.004) and
      with mantle cell lymphoma (AA genotype: OR, 0.20; P = 0.01) that remains
      significant after adjustment for the false discovery rate, but not with diffuse
      large B-cell lymphoma. These data support the hypothesis that genetic variation
      in the H2AFX gene influences genetic susceptibility or resistance to some
      subtypes of NHL by contributing to the maintenance of genome stability.

PMID- 17548671
TI  - Human papillomavirus prevalence and type distribution in male anogenital sites
      and semen.
AB  - BACKGROUND: Human papillomavirus (HPV) is sexually transmitted and causes
      cervical cancer. Although HPV can infect men and women, little is known about
      infection in men. Specifically, the prevalence of type-specific HPV infection and
      the distribution of infections by anogenital anatomic site in men are
      incompletely characterized. METHODS: We tested 463 men ages 18 to 40 years for
      HPV at the glans/corona, penile shaft, scrotum, urethra, perianal area, anal
      canal, and in a semen sample. Eligible men acknowledged no history of genital
      warts and had sexual intercourse with a woman within the past year. HPV testing
      by PCR and reverse line blot genotyping for 37 types was conducted on each of the
      specimens from the seven sampling sites. RESULTS: When HPV results from any
      sampling site were considered, 237 (51.2%) men were positive for at least one
      oncogenic or nononcogenic HPV type, and another 66 (14.3%) men were positive for
      an unclassified HPV type. The types with the highest prevalence were HPV-16
      (11.4%) and 84 (10.6%). External genital samples (glans/corona, shaft, and
      scrotum) were more likely than anal samples to contain oncogenic HPV (25.1%
      versus 5.0%). HPV-positive penile shaft and glans/corona samples were also more
      likely to be infected with multiple HPV types than other sites. CONCLUSIONS: More
      complete anogenital sampling and sensitive detection for 37 HPV types resulted in
      a higher HPV prevalence in primarily asymptomatic men than reported previously.
      The penile shaft was the site most likely to be HPV positive and harbored the
      greatest proportion of multiple type and oncogenic infections. These results have
      implications for research of HPV among men and transmission between partners.

PMID- 17548672
TI  - Polymorphisms in oxidative stress-related genes are not associated with prostate
      cancer risk in heavy smokers.
AB  - Oxidative stress, associated with aging and inflammation, is likely to play a
      role in the etiology of prostate cancer. We evaluated potential associations
      between gene variants that result in reduced neutralization of reactive oxygen
      species (ROS; MnSOD Ala-16Val, CAT -262 C>T, and GPX1 Pro200Leu) and prostate
      cancer risk among 724 men with incident prostate cancer who participated in the
      Carotene and Retinol Efficacy Trial (CARET) cohort, a randomized trial for the
      prevention of lung cancer among men with a history of smoking and/or asbestos
      exposure. Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated
      by logistic regression. Nested case-control analyses included study participants
      with available DNA (n = 533 cases and 1,470 controls), matched for race, age, and
      length of follow-time. Overall, there were no associations between genotypes of
      MnSOD, CAT, and GPX1 and prostate cancer risk, although among men diagnosed
      before age 65, CAT TT genotype was associated with increased risk (OR, 2.0; 95%
      CI, 0.97-3.95). Further analyses stratified by factors related to environmental
      oxidative stress exposures did not modify associations. When calculating the
      number of risk alleles of MnSOD, CAT, and GPX1 hypothetically related to reduced
      protection against ROS, there was a nonsignificant relationship between prostate
      cancer and carriage of five or more risk alleles, in comparison to men with less
      than five risk alleles (OR, 2.0; 95% CI, 0.90-4.42). In conclusion, it does not
      seem that variants in MnSOD, CAT, or GPX1 have an influence on prostate cancer
      risk in this cohort of men who were smokers or exposed to asbestos, although it
      is possible that cumulative defects in protection from oxidative stress may
      result in increased risk of the disease.

PMID- 17548673
TI  - Serum insulin-like growth factor (IGF)-I and IGF-binding protein-3 concentrations
      and prostate cancer risk: results from the European Prospective Investigation
      into Cancer and Nutrition.
AB  - BACKGROUND: Some studies suggest that elevated serum insulin-like growth factor
      (IGF)-I concentrations are associated with an increased risk of prostate cancer
      and, in particular, with an increased risk of advanced-stage prostate cancer.
      METHODS: We analyzed the association between prediagnostic serum concentrations
      of IGF-I and IGF-binding protein-3 (IGFBP-3) and prostate cancer risk in a case
      control study nested in the European Prospective Investigation into Cancer and
      Nutrition. This study includes 630 incident prostate cancer cases and 630 matched
      control subjects. Odds ratios and their 95% confidence intervals (95% CI) were
      calculated for prostate cancer risk associated with increasing IGF-I and IGFBP-3
      concentrations using conditional logistic regression. RESULTS: The risk of total
      prostate cancer in the highest versus the lowest third of serum peptide
      concentration was 1.35 (95% CI, 0.99-1.82; Ptrend = 0.08) for IGF-I, 1.39 (95%
      CI, 1.02-1.89; Ptrend = 0.12) for the IGF-I residuals after adjusting for IGFBP
      3, 1.22 (95% CI, 0.92-1.64; Ptrend = 0.38) for IGFBP-3, and 1.01 (95% CI, 0.74
      1.37; Ptrend = 0.75) for the IGFBP-3 residuals after adjusting for IGF-I. There
      was no significant difference in the association of peptide hormones and prostate
      cancer by stage of disease, although the association of serum IGF-I concentration
      with risk was slightly stronger for advanced-stage disease; the odds ratio for
      the highest versus the lowest third was 1.65 (95% CI, 0.88-3.08; Ptrend = 0.21)
      for IGF-I and 1.76 (95% CI, 0.92-3.40; Ptrend = 0.11) for IGF-I adjusted for
      IGFBP-3. CONCLUSIONS: In this large nested case-control study, serum IGF-I
      concentration is not strongly associated with prostate cancer risk, although the
      results are compatible with a small increase in risk, particularly for advanced
      stage disease; no association for IGFBP-3 was observed.

PMID- 17548674
TI  - Supplemental and dietary vitamin E intakes and risk of prostate cancer in a large
      prospective study.
AB  - Supplemental vitamin E (alpha-tocopherol) has been linked to lower prostate
      cancer incidence in one randomized trial and several, although not all,
      observational studies. The evidence regarding dietary intake of individual
      vitamin E isoforms and prostate cancer is limited and inconclusive, however. We
      prospectively examined the relations of supplemental vitamin E and dietary
      intakes of alpha-, beta-, gamma-, and delta- tocopherols to prostate cancer risk
      among 295,344 men, ages 50 to 71 years and cancer-free at enrollment in 1995 to
      1996, in the NIH-AARP Diet and Health Study. At baseline, participants completed
      a questionnaire that captured information on diet, supplement use, and other
      factors. Proportional hazards models were used to estimate relative risks (RR)
      and 95% confidence intervals (95% CI) of prostate cancer. During 5 years of
      follow-up, 10,241 incident prostate cancers were identified. Supplemental vitamin
      E intake was not related to prostate cancer risk (for >0-99, 100-199, 200-399,
      400-799, and > or = 800 IU/d versus never use: RR, 0.97, 0.89, 1.03, 0.99, and
      0.97 (95% CI, 0.87-1.07) respectively; Ptrend = 0.90). However, dietary gamma
      tocopherol, the most commonly consumed form of vitamin E in the United States,
      was significantly inversely related to the risk of advanced prostate cancer (for
      highest versus lowest quintile: RR, 0.68; 95% CI, 0.56-0.84; Ptrend = 0.001).
      These results suggest that supplemental vitamin E does not protect against
      prostate cancer, but that increased consumption of gamma-tocopherol from foods is
      associated with a reduced risk of clinically relevant disease. The potential
      benefit of gamma-tocopherol for prostate cancer prevention deserves further
      attention.

PMID- 17548675
TI  - Effect of delays in processing blood samples on measured endogenous plasma sex
      hormone levels in women.
AB  - Time spent in transit may affect the concentration of various constituents of
      collected blood samples and, consequently, results of sex hormone assays. Whole
      blood was collected from 46 women, and one third was processed immediately, one
      third was stored at ambient conditions (22 degrees C) for 1 day, and one third
      was stored for 2 days. Estradiol concentration increased by 7.1% [95% confidence
      interval (95% CI), 3.2-11.3%] after a delay in processing of 1 day and by 5.6%
      (95% CI, 0.2-11.4%) after a delay in processing of 2 days; the change was most
      apparent at lower than median concentrations. Progesterone concentrations showed
      no substantial change. Testosterone concentrations changed by 23.9% (95% CI, 17.8
      30.3%) after a delay of 1 day but little thereafter. The sex hormone-binding
      globulin concentration decreased by 6.6% (95% CI, 4.6-8.6%) and 10.9% (95% CI,
      8.1-13.6%), follicle-stimulating hormone increased by 7.4% (95% CI, 4.2-10.7%)
      and 13.9% (95% CI, 8.7-19.3%), and luteinizing hormone increased by 4.9% (95% CI,
      1.3-8.5%) and 6.7% (95% CI, 2.2-11.5%) after a delay in processing of 1 and 2
      days. Increases in calculated values for biologically available levels of
      estradiol and testosterone were greater than the increases seen in measured total
      hormone concentrations. Similar changes are likely when samples are delayed in
      transit, and evidence of etiology may be obscured unless study designs or
      analyses take into account processing delays.

PMID- 17548676
TI  - Association of polymorphisms in one-carbon metabolism genes and postmenopausal
      breast cancer incidence.
AB  - The interconversion of folates by the one-carbon metabolism pathway is essential
      for the synthesis of precursors used in DNA synthesis, repair, and methylation.
      Perturbations in this pathway can disrupt these processes and are hypothesized to
      facilitate carcinogenesis. We investigated associations of 25 candidate
      polymorphisms in nine one-carbon metabolism genes with risk of postmenopausal
      breast cancer using 502 cases and 505 controls from the Cancer Prevention II
      Nutrition Cohort. Four single nucleotide polymorphisms (SNP) in three different
      genes were significantly associated with breast cancer. The nonsynonymous R134K
      SNP in methylenetetrahydrofolate dehydrogenase/methenyltetrahydrofolate
      cyclohydrolase/formyltetrahydrofolate synthase [MTHFD1; odds ratio (OR), 1.40;
      95% confidence interval (95% CI), 1.06-1.85 for CT + TT] and an intronic SNP in
      formyltetrahydrofolate dehydrogenase (FTHFD; OR, 2.23; 95% CI, 1.09-4.54 for CC)
      were associated with a significant increase in risk. Significantly decreased risk
      was associated with an intronic SNP in FTHFD (OR, 0.75; 95% CI, 0.58-0.98 for CT
      + CC) and the A360A SNP in cystathionine beta-synthase (CBS; OR, 0.63; 95% CI,
      0.41-0.96 for TT). The presence of at least one variant from both the
      methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C SNPs was also
      associated with increased risk (OR, 2.16; 95% CI, 1.34-3.48 for 677 CT + TT/1,298
      AC + CC). Investigations into interactions of the associated SNPs with each other
      and with dietary factors yielded inconclusive results. Our findings indicate that
      genetic variation in multiple one-carbon metabolism genes may influence risk of
      postmenopausal breast cancer and may involve changes in methyl donor synthesis.
      However, larger studies are needed to further examine gene/gene and gene/diet
      interactions in this pathway.

PMID- 17548677
TI  - Comparison of a new and existing method of mammographic density measurement:
      intramethod reliability and associations with known risk factors.
AB  - BACKGROUND: Mammographic density is one of the strongest risk factors for breast
      cancer. It is commonly measured by an interactive threshold method that does not
      fully use information contained in a mammogram. An alternative fully automated
      standard mammogram form (SMF) method measures density using a volumetric
      approach. METHODS: We examined between-breast and between-view agreement,
      reliability, and associations of breast cancer risk factors with the threshold
      and SMF measures of breast density on the same set of 1,000 digitized films from
      250 women who attended routine breast cancer screening by two-view mammography in
      2004 at a London population-based screening center. Data were analyzed using
      random-effects models on transformed percent density. RESULTS: Median
      (interquartile range) percent densities were 12.8% (5.0-22.3) and 21.8% (18.4
      26.6) in the threshold and SMF methods, respectively. There was no evidence of
      systematic differences between left-right breasts or between views in either
      method. Reliability of a single measurement was lower in the SMF than in the
      threshold method (0.77 versus 0.92 for craniocaudal and 0.68 versus 0.89 for
      mediolateral oblique views). Increasing body mass index and parity were
      associated with reduced density in both methods; however, an increase in density
      with hormone replacement therapy use was found only with the threshold method.
      CONCLUSION: Established properties of mammographic density were observed for SMF
      percent density; however, this method had poorer left-right reliability than the
      threshold method and has yet to be shown to be a predictor of breast cancer risk.

PMID- 17548678
TI  - Associations of circulating C-reactive protein and interleukin-6 with survival in
      women with and without cancer: findings from the British Women's Heart and Health
      Study.
AB  - BACKGROUND: Inflammation is associated with worse prognosis and survival in many
      cancers. Our aim was to investigate the associations of circulating C-reactive
      protein (CRP) and interleukin-6 (IL-6) concentrations with all-cause mortality in
      cancer patients and to determine whether any associations were specific to
      malignancy. METHOD: We used data from the British Women's Heart and Health Study,
      a cohort of 4,286 women aged 60 to 79 years. We investigated the associations
      between CRP, IL-6, and survival in women with and without cancer using Cox
      regression and assessed the interaction between cancer status and these
      inflammatory markers to determine whether these associations differed according
      to cancer status. RESULTS: Elevated CRP and IL-6 were associated with decreased
      survival in women with cancer [unadjusted hazard ratio per doubling of CRP, 1.22,
      95% confidence interval (95% CI), 1.03, 1.46; and per doubling of IL-6, 1.52, 95%
      CI, 1.25, 1.86] and in women without cancer [CRP: 1.24 (1.12, 1.37); IL-6: 1.53
      (1.35, 1.75)]. Adjustment for age, body mass index, physical activity level,
      socioeconomic position, HRT use, and tobacco smoking did not change these
      associations. After mutual adjustment, IL-6 but not CRP was independently
      associated with survival. We found no strong evidence that these associations
      differed between cancer patients and cancer-free women. CONCLUSIONS: Elevated CRP
      and IL-6 concentrations were similarly associated with an increased risk of death
      in elderly women with and without cancer. Thus, in this group, these markers are
      likely to be indicators of non-cancer comorbidities rather than related to the
      malignancy itself.

PMID- 17548679
TI  - Different risk factor profiles for mucinous and nonmucinous ovarian cancer:
      results from the Danish MALOVA study.
AB  - OBJECTIVES: The aim of the study was to examine the overall risk factors for
      epithelial ovarian cancer and according to histologic subtypes. MATERIALS AND
      METHODS: Ovarian cancer cases and controls were recruited from 1995 to 1999, and
      personal interviews were conducted. A total of 554 cases and 1,564 randomly
      selected controls were included. The analyses were done using multiple logistic
      regression models. RESULTS: The overall risk of ovarian cancer decreased with
      ever being pregnant [odds ratios (OR), 0.40; 95% confidence intervals (CI), 0.30
      0.55], with increasing pregnancies (OR, 0.63; 95% CI, 0.45-0.87 and OR, 0.51; 95%
      CI, 0.37-0.69 for two and three pregnancies as compared with one), and with older
      age at first and last pregnancy, respectively. Increasing years of ovulation was
      a very strong risk factor with a 7% to 8% increase in risk for each year of
      ovulation. Use of oral contraceptives (OR, 0.67, 95% CI, 0.53-0.85) and longer
      duration of use were associated with a decreased risk of ovarian cancer. Ever use
      of hormone replacement therapy increased the overall risk (OR, 1.30; 95% CI, 1.05
      1.61). For all those variables, the effect was present for serous tumors,
      endometrioid tumors, and tumors of other histologies, but not for mucinous
      tumors. In contrast, current smoking was a risk factor only for mucinous tumors
      (OR, 1.78; 95% CI, 1.01-3.15) and increasing body mass index tended to increase
      the risk especially for mucinous and endometrioid tumors. CONCLUSIONS: We
      confirmed already known risk factors for ovarian cancer, and we observed
      significant differences in the risk profiles between mucinous and nonmucinous
      tumors indicating different etiologies.

PMID- 17548680
TI  - Exposure to magnetic fields and survival after diagnosis of childhood leukemia: a
      German cohort study.
AB  - Inspired by a recent U.S. study showing poorer survival among children with acute
      lymphoblastic leukemia (ALL) exposed to magnetic fields above 0.3 microT, we
      examine this relationship in a German cohort of childhood leukemia cases derived
      from previous population-based case-control studies conducted between 1992 and
      2001. A total of 595 ALL cases with 24-h magnetic field measurements are included
      in the analysis with a median follow-up of 9.5 years. We calculate the hazard
      ratios (HR) using the Cox proportional hazards model for overall survival,
      adjusted for age at diagnosis, calendar year of diagnosis, and gender. Elevated
      hazards are found for exposures between 0.1 and 0.2 microT [HR, 2.6; 95%
      confidence interval (95% CI), 1.3-5.2], based on 34 cases with 9 deaths as well
      as for exposures above 0.2 microT (HR, 1.6; 95% CI, 0.6-4.4), based on 18 cases
      with 4 deaths. After adjustment for prognostic risk group, the hazard for
      exposures above 0.2 microT increases to HR, 3.0 (95% CI, 0.9-9.8). In conclusion,
      this study is generally consistent with the previous finding; however, we report
      the excess risk at field levels lower than those in the U.S. study. In all, the
      evidence is still based on small numbers, and a biological mechanism to explain
      the findings is not known.

PMID- 17548681
TI  - MDR1 gene variants, indoor insecticide exposure, and the risk of childhood acute
      lymphoblastic leukemia.
AB  - OBJECTIVE: The multidrug resistance (MDR) 1 gene encodes a membrane transporter
      called P-glycoprotein, which plays an important role in protecting cells against
      lipophilic xenobiotics by way of an ATP-dependent cellular efflux mechanism.
      Among children enrolled in the Northern California Childhood Leukemia Study, we
      examined the susceptibility conferred by MDR1 single nucleotide polymorphisms
      (SNP) and predicted haplotypes and whether they modify the association between
      indoor insecticide exposure and risk of childhood acute lymphoblastic leukemia
      (ALL). METHODS: Buccal cell DNA from ALL cases (n = 294) and controls (n = 369)
      individually matched on gender, date of birth, Hispanic status, and maternal race
      were whole genome amplified and genotyped for four MDR1 SNPs, T-129C (rs3213619),
      C1236T (rs1128503), G2677T/A (rs2032582), and C3435T (rs1045642). Detailed and
      time-specific information on household pesticide use was obtained using in-home
      interviews with the mother. RESULTS: Allele frequencies in non-Hispanic White and
      Hispanic controls were similar, and with the exception of T-129C, seemed to be in
      strong linkage disequilibrium. Overall, the SNPs considered individually or
      within haplotypes (C1236T-G2677T/A-C3435T) were not significantly associated with
      childhood ALL. However, we observed strong evidence of a differential effect of
      indoor insecticide exposure (interaction odds ratio, 0.31; 95% confidence
      interval, 0.15-0.64; P = 0.025) on risk of ALL between carriers and noncarriers
      of haplotype CGC. CONCLUSION: These preliminary data suggest that children
      carrying the haplotype CGC may be less susceptible to the leukemogenic effects of
      indoor insecticide exposures. Future studies are needed to confirm these
      findings.

PMID- 17548682
TI  - Promoter hypermethylation of tumor suppressor genes in urine from patients with
      cervical neoplasia.
AB  - We examined the feasibility of using detection of high-risk human papillomavirus
      (HPV) DNA in combination with the presence of aberrantly methylated genes (DAPK1,
      RARB, TWIST1, and CDH13) for urine-based cervical cancer screening. Urine samples
      from 129 Senegalese women, aged 35 years or older, 110 with (same day) biopsy
      proven cervical neoplasia [cervical intraepithelial neoplasia grade 1 (CIN-1): n
      = 9; CIN-2-3/carcinoma in situ (CIS): n = 29; invasive cervical cancer (ICC): n =
      72], and 19 without cervical neoplasia on biopsy were examined. Hypermethylation
      of at least one of the four genes identified 62% of ICC and 28% of CIN-2-3/CIS
      and was present in only 4% of CIN-1 or normal urines. High-risk HPV DNA was
      detected in urine in 70% of those with biopsy-proven ICC, 59% of those with CIN-2
      3/CIS on biopsy, 44% of those with CIN-1 on biopsy, and only 11% of women
      negative for cervical neoplasia on biopsy. Urine-based detection of either high
      risk HPV or hypermethylation of any of the four genes identified 84% of ICC, 64%
      of CIN-2-3/CIS, 44% of CIN-1, but only 19% of women negative for cervical
      neoplasia. The sensitivity for detection of CIN-2-3/CIS/ICC by high-risk HPV DNA
      or aberrant DNA methylation of four genes seems to be comparable to that of an
      exfoliated cervical cytology. This study shows the potential feasibility of using
      molecular markers detected in urine for cervical cancer screening.

PMID- 17548683
TI  - Triallelic single nucleotide polymorphisms and genotyping error in genetic
      epidemiology studies: MDR1 (ABCB1) G2677/T/A as an example.
AB  - Accurate measurement of allele frequencies between population groups with
      differing sensitivities to disease is fundamental to genetic epidemiology.
      Genotyping errors can markedly influence the biological conclusions of a study.
      This issue may be especially important now there is increasing recognition of
      triallelic single nucleotide polymorphisms (SNPs) in the genome and their
      possible role in diseases like inflammatory bowel disease. For example, the MDR1
      (ABCB1) SNP G2677/T/A was, like many other triallelic SNPs, originally described
      as diallelic. Here, we report a comprehensive analyses of estimated allele
      frequencies of this SNP in a set of 73 human DNA samples, comparing six commonly
      used genotyping methods (Applied Biosystems Taqman, Roche LightCycler melting
      analysis, allelic discrimination PCR, DNA sequencing, Sequenom, and RFLP) from
      the angle of their error potential. Only Sequenom and DNA sequencing provided
      accurate measurements, if we had not had prior knowledge of the triallelic nature
      of this SNP. The other tested methods (with the exception of LightCycler) failed
      to show any indication of the presence of the rare third A- allele in a diallelic
      assay. Although most of the errors were due to the inability to detect the third
      allele, all methods except Sequenom and sequencing produced errors for the
      detection of the two common alleles G and T (LightCycler, 6 errors; PCR, 4
      errors; RFLP, 2 errors; Taqman, 1 error). There is considerable variability in
      the reported frequencies of the different alleles of the MDR1 G2677/T/A SNP, and
      the role of this SNP in the etiology of inflammatory bowel disease has been
      controversial. Our data emphasize the importance of choosing the appropriate
      method for SNP detection and lead us to suggest that part of the previously
      reported variation may reflect artifacts associated with the different genotyping
      methodologies used. The failure to recognize the triallic nature of a SNP may
      lead to underestimations of real genetic associations.

PMID- 17548684
TI  - Path analysis of biomarkers of exposure and early biological effects among coke
      oven workers exposed to polycyclic aromatic hydrocarbons.
AB  - Many host factors or biomarkers are involved in the process of early DNA damage
      induced by occupational exposure to polycyclic aromatic hydrocarbons (PAH) as
      seen in coke-oven workers. This paper aimed to identify complicated causal
      interrelationship of various biomarkers using the path analysis. In this
      analysis, we included 235 subjects (166 coke-oven workers and 69 nonexposed
      controls) whose data on the comet assay (e.g., Olive tail moment) and cytogenetic
      analysis of peripheral blood lymphocytes as well as urinary 1-hydroxypyrene (1
      OHP) were available. The path analysis showed that coke-oven exposure and tobacco
      smoke were both significant predictors of the concentrations of urinary 1-OHP (P
      < 0.05), with a coefficient of determination of 0.75. The factors having
      significant influence on the Olive tail moment were in the following order:
      urinary 1-OHP > XRCC1-exon 9 variant genotype > ERCC2-exon 10 variant genotype >
      XRCC1-exon 6 variant genotype, with a coefficient of determination of 0.22. The
      variables of relative importance in influencing on cytokinesis-block micronucleus
      frequencies were in the following order: coke-oven exposure > urinary 1-OHP > age
      > mEH3 variant genotype > ERCC2-exon 10 variant genotype > XRCC1-exon 6 variant
      genotype, with a coefficient of determination of 0.27. These results indicated
      that exogenous agents, especially the coke-oven exposure, played a more important
      role than the genotypes in the induction of early genetic damage. In conclusion,
      the path analysis seemed to be an alternative statistical approach for the
      ascertainment of complicated association among related biomarkers for the
      assessment of occupational exposure.

PMID- 17548685
TI  - Clinical biology of esophageal adenocarcinoma after surgery is influenced by
      nuclear factor-kappaB expression.
AB  - BACKGROUND: The expression of transcriptional factor nuclear factor kappaB (NF
      kappaB) in untreated esophageal cancer specimens from patients who receive
      preoperative chemoradiation is associated with aggressive clinical biology. We
      hypothesized that nuclear NF-kappaB would define clinical biology even when
      surgery is used as primary therapy. METHODS: Consecutive patients who did not
      receive any preoperative therapy were selected. Surgical cancer specimens were
      examined for nuclear NF-kappaB and correlated with overall survival (OS) and
      disease-free survival (DFS). RESULTS: One hundred twenty-three patients (stage I,
      9%; stage II, 24%; stage III, 53%; stage IV, 15%) with adenocarcinoma who
      underwent surgery as primary therapy were analyzed. Most patients were men (90%)
      and the median age was 63 years. For all 123 patients, the median DFS was 21
      months and the median OS was 28 months. Nuclear NF-kappaB was associated with
      shortened DFS (P = 0.001) in 123 patients but also in stage II (P = 0.03) and
      stage III (P = 0.04). Nuclear NF-kappaB was associated with shortened OS (P =
      0.002) in 123 patients and in stage II (P = 0.04) and showed trend in stage III
      (P = 0.17). Numbers are too small for stages I and IV. In multivariate models,
      nuclear NF-kappaB was an independent predictor for both DFS and OS (P = 0.005 and
      P = 0.01). CONCLUSIONS: Our data are the first to show that NF-kappaB status
      significantly correlates with DFS and OS for patients with esophageal
      adenocarcinoma undergoing surgery as primary therapy. NF-kappaB is an independent
      prognosticator of outcome, even for individual stages (e.g., stages II and III).
      More comprehensive molecular studies could help the design of strategies to
      individualize therapy of esophageal adenocarcinoma.

PMID- 17548686
TI  - The angiotensin II/angiotensin II receptor system correlates with nodal spread in
      intestinal type gastric cancer.
AB  - We aimed to substantiate the putative significance of angiotensin II receptor
      type 1 (AT1R) and type 2 (AT2R) for gastric cancer biology by investigating the
      correlation of their expression with various clinicopathologic variables and
      patient survival. Local expression of AT1R, AT2R, and angiotensin-converting
      enzyme (ACE) was investigated by immunohistochemistry in tumor and corresponding
      nontumor specimens obtained from 100 patients with gastric cancer, and compared
      with the ACE insertion/deletion gene polymorphism. AT1R and AT2R were found in
      the tumor epithelial cells of 26 (26%) and 95 (95%) patients, respectively. AT1R
      was significantly more prevalent (P < 0.001) in intestinal type gastric cancer
      than in diffuse type gastric cancer. In intestinal type gastric cancer, its
      expression correlated with the N category (P = 0.009) and the International Union
      Against Cancer tumor stage (P = 0.024). AT1R+ intestinal type gastric cancers had
      a larger number of lymph node metastases (P = 0.026), a higher International
      Union Against Cancer tumor stage (P = 0.032), and a shorter survival time (P =
      0.009) than AT1R- tumors. Multivariate analysis with lymph nodes as a dependent
      variable showed that AT1R status and ACE-I/D gene polymorphism are independent
      risk factors. Irrespective of the genotype, AT1R+ gastric cancers had a relative
      risk of lymph node metastases of 4.40 (95% confidence interval, 1.30-14.86). When
      the ACE genotype was included, the relative risk of having lymph node metastases
      increased considerably in AT1R+ tumors being heterozygous or homozygous for the
      ACE D allele (odds ratio, 19.00; 95% confidence interval, 1.45-248.24). Our study
      shows that AT1R and AT2R are expressed locally in gastric cancer and that the
      combination of AT1R expression and ACE I/D gene polymorphism correlates with
      nodal spread in intestinal type gastric cancer.

PMID- 17548687
TI  - Acceleration to death from liver cancer in people with hepatitis B viral
      mutations detected in plasma by mass spectrometry.
AB  - Liver cancer is the leading cause of cancer death in many regions of the world.
      With the goal to discover biomarkers that reflect subsets of high-risk
      individuals and their prognosis, we nested our study in a male cohort of 5,581
      hepatitis B surface antigen carriers in Qidong, People's Republic of China, who
      were recruited starting in 1989. By December 2003, 667 liver cancer cases were
      diagnosed in this group and plasma samples collected at the initial screening at
      enrollment were available in 515 cases who had succumbed to liver cancer.
      Hepatitis B virus (HBV) DNA could be isolated in 355 (69%) of these samples. In
      14%, 15%, 19%, 31%, and 22%, screening took place at < or = 1.5, 1.51 to 3, 3.01
      to 5, 5.01 to 9, and > 9 years before death, respectively; and 39% died at age
      below 45 years. The relation between mutations in HBV and time to death were
      determined by logistic regression for the odds of mutation and by survival
      analyses methods with age as the time scale. In 279 (79%) of these individuals,
      the samples contained a two-nucleotide 1762T/1764A HBV mutation. Sixteen samples
      lacking the 1762T/1764A mutation had novel mutations elsewhere in the 1761 to
      1767 region of the HBV genome. There was a statistically significant difference
      (P = 0.012) for the high prevalence of the HBV mutations in the men who died from
      hepatocellular carcinoma under the age of 45 years relative to those who died
      after 55 years of age and HBV mutations accelerated death (relative hazard, 1.40;
      95% confidence interval, 1.06-1.85) and that the effect was attenuated by age
      from 2.04 for age 35 years to 1.0 for age 65 years with the 90% confidence band
      being above 1 for ages < 50 years. These findings provide a conceptual framework
      to explain the acceleration of mortality in individuals infected with HBV.

PMID- 17548688
TI  - Prospective cohort study of green tea consumption and colorectal cancer risk in
      women.
AB  - Tea and its constituents have shown anticarcinogenic activities in in vitro and
      animal studies. Epidemiologic studies, however, have been inconsistent. We
      prospectively evaluated the association between green tea consumption and
      colorectal cancer (CRC) risk in a cohort of 69,710 Chinese women aged 40 to 70
      years. Information on tea consumption was assessed through in-person interviews
      at baseline and reassessed 2 to 3 years later in a follow-up survey. During 6
      years of follow-up, 256 incident cases of CRC were identified. The multivariate
      relative risk of CRC was 0.63 (95% confidence interval, 0.45-0.88) for women who
      reported drinking green tea regularly at baseline compared with nonregular tea
      drinkers. A significant dose-response relationship was found for both the amount
      of tea consumed (Ptrend = 0.01) and duration in years of lifetime tea consumption
      (Ptrend = 0.006). The reduction in risk was most evident among those who
      consistently reported to drink tea regularly at both the baseline and follow-up
      surveys (relative risk, 0.43; 95% confidence interval, 0.24-0.77). The inverse
      association with regular tea drinking was observed for both colon and rectal
      cancers. This study suggests that regular consumption of green tea may reduce CRC
      risk in women.

PMID- 17548689
TI  - Low-positive antibody titer against Helicobacter pylori cytotoxin-associated gene
      A (CagA) may predict future gastric cancer better than simple seropositivity
      against H. pylori CagA or against H. pylori.
AB  - BACKGROUND: To investigate the IgG antibody titer against Helicobacter pylori
      CagA as a risk factor for future noncardia gastric cancer. METHODS: A nested case
      control study was done in the longitudinal cohort of atomic bomb survivors using
      stored sera before diagnosis (mean, 2.3 years). Enrolled were 299 cancer cases
      and 3 controls per case selected from cohort members matched on age, gender,
      city, and time and type of serum storage and countermatched on radiation dose.
      RESULTS: H. pylori IgG seropositive with CagA IgG low titer was the strongest
      risk factor for noncardia gastric cancer [relative risk (RR), 3.9; 95% confidence
      interval (95% CI), 2.1-7.0; P < 0.001], especially for intestinal-type tumor (RR,
      9.9, 95% CI, 3.5-27.4; P < 0.001), compared with other risk factors, H. pylori
      IgG seropositive with CagA IgG negative (RR, 2.2; 95% CI, 1.3-3.9; P = 0.0052),
      H. pylori IgG seropositive with CagA IgG high titer (RR, 2.0; 95% CI, 1.3-3.2; P
      = 0.0022), chronic atrophic gastritis (RR, 2.4; 95% CI, 1.8-3.3; P < 0.001),
      current smoking (RR, 2.3; 95% CI, 1.4-3.5; P < 0.001), or radiation dose (RR,
      2.1; 95% CI, 1.2-3.1; P = 0.00193). Current smoking showed significantly higher
      risk for diffuse-type than intestinal-type tumors (P = 0.0372). Radiation risk
      was significant only for nonsmokers, all noncardia, and diffuse-type gastric
      cancers. CONCLUSIONS: A low CagA IgG titer is a useful biomarker to identify a
      high-risk group and it also provides a clue to understanding host-pathogen
      interaction.

PMID- 17548690
TI  - Allergy-related polymorphisms influence glioma status and serum IgE levels.
AB  - Previous studies have shown that glioma patients report allergies less frequently
      than controls, harbor lower atopy-associated IgE levels, and harbor different
      frequencies of polymorphisms in the IL13 and IL4 pathways than controls. We
      sought to confirm this latter result and extend the analysis to IgE levels.
      Glioma patients (n = 456) and controls (n = 541) were genotyped for genetic
      variants in IL4, IL4R, and IL13 and tested for total IgE levels (n = 248 controls
      and 289 cases). Among Whites, IL4 and IL4R polymorphisms and haplotypes were
      neither significantly associated with IgE levels in controls nor associated with
      glioma status. IL13 R110G and C-1112T were associated with increased IgE levels
      in controls (P < 0.001 and P = 0.04, respectively), and IL13 C-1112T was
      inversely associated with case-control status (P = 0.05, test for trend in dose
      model). An IL4R haplotype was borderline associated with increased risk in case
      control analysis [odds ratio (OR), 1.5; 95% confidence interval (95% CI), 1.0
      2.3]. In addition, a rare haplotype for IL4 was associated with decreased risk
      (OR, 0.23; 95% CI, 0.07-0.83), and a common haplotype in IL13 was associated with
      decreased risk (OR, 0.73; 95% CI, 0.53-1.00). Our data provide evidence for a
      role of IL13 polymorphisms on IgE levels and a role for IL4, IL4R, and IL13
      haplotypes on case-control status. We did not find any evidence that the
      interleukin (IL) polymorphisms exerted their effect on glioma risk via their
      effects on IgE levels. Further exploration of immune susceptibility factors,
      including genetics, in glioma etiology is advisable.

PMID- 17548692
TI  - Phase I dose escalation pharmacokinetic study in healthy volunteers of
      resveratrol, a potential cancer chemopreventive agent.
AB  - The red grape constituent resveratrol possesses cancer chemopreventive properties
      in rodents. The hypothesis was tested that, in healthy humans, p.o.
      administration of resveratrol is safe and results in measurable plasma levels of
      resveratrol. A phase I study of oral resveratrol (single doses of 0.5, 1, 2.5, or
      5 g) was conducted in 10 healthy volunteers per dose level. Resveratrol and its
      metabolites were identified in plasma and urine by high-performance liquid
      chromatography-tandem mass spectrometry and quantitated by high-performance
      liquid chromatography-UV. Consumption of resveratrol did not cause serious
      adverse events. Resveratrol and six metabolites were recovered from plasma and
      urine. Peak plasma levels of resveratrol at the highest dose were 539 +/- 384
      ng/mL (2.4 micromol/L, mean +/- SD; n = 10), which occurred 1.5 h post-dose. Peak
      levels of two monoglucuronides and resveratrol-3-sulfate were 3- to 8-fold
      higher. The area under the plasma concentration curve (AUC) values for
      resveratrol-3-sulfate and resveratrol monoglucuronides were up to 23 times
      greater than those of resveratrol. Urinary excretion of resveratrol and its
      metabolites was rapid, with 77% of all urinary agent-derived species excreted
      within 4 h after the lowest dose. Cancer chemopreventive effects of resveratrol
      in cells in vitro require levels of at least 5 micromol/L. The results presented
      here intimate that consumption of high-dose resveratrol might be insufficient to
      elicit systemic levels commensurate with cancer chemopreventive efficacy.
      However, the high systemic levels of resveratrol conjugate metabolites suggest
      that their cancer chemopreventive properties warrant investigation.

PMID- 17548691
TI  - Associations between smoking, polymorphisms in polycyclic aromatic hydrocarbon
      (PAH) metabolism and conjugation genes and PAH-DNA adducts in prostate tumors
      differ by race.
AB  - Polycyclic aromatic hydrocarbon (PAH)-DNA adducts may induce mutations that
      contribute to carcinogenesis. We evaluated potential associations between smoking
      and polymorphisms in PAH metabolism [CYP1A1 Ile 462Val, CYP1B1 Ala 119Ser and Leu
      432Val, microsomal epoxide hydrolase (mEH) Tyr 113His and His139Arg, CYP3A4 A(
      392)G] and conjugation [glutathione S-transferase (GST) M1 null deletion, GSTP1
      Ile 105Val] genes and PAH-DNA adduct levels (measured by immunohistochemistry) in
      tumor and nontumor prostate cells in 400 prostate cancer cases. Although no
      statistically significant associations were observed in the total sample,
      stratification by ethnicity revealed that Caucasian ever smokers compared with
      nonsmokers had higher adduct levels in tumor cells (mean staining intensity in
      absorbance units +/- SE, 0.1748 +/- 0.0052 versus 0.1507 +/- 0.0070; P = 0.006),
      and Caucasians carrying two mEH 139Arg compared with two 139His alleles had lower
      adducts in tumor (0.1320 +/- 0.0129 versus 0.1714 +/- 0.0059; P = 0.006) and
      nontumor (0.1856 +/- 0.0184 versus 0.2291 +/- 0.0085; P = 0.03) cells. African
      Americans with two CYP1B1 432Val compared with two 432Ile alleles had lower
      adducts in tumor cells (0.1600 +/- 0.0060 versus 0.1970 +/- 0.0153; P = 0.03).
      After adjusting for smoking status, carrying the putative "high-risk" genotype
      combination, the faster metabolism of PAH-epoxides to PAH-diol-epoxides (CYP1B1
      432Val/Val and mEH 139Arg/Arg) with lower PAH-diol-epoxide conjugation (GSTP1
      (105)Ile/Ile), was associated with increased adducts only in Caucasian nontumor
      cells (0.2363 +/- 0.0132 versus 0.1920 +/- 0.0157; P= 0.05). We present evidence,
      for the first time in human prostate that the association between smoking and PAH
      DNA adducts differs by race and is modified by common genetic variants.

PMID- 17548693
TI  - Serum and dietary vitamin E in relation to prostate cancer risk.
AB  - Alpha-tocopherol supplementation (50 mg daily for 5-8 years) reduced prostate
      cancer incidence by 32% in the alpha-Tocopherol, beta-Carotene Cancer Prevention
      Study. We investigated whether serum alpha-tocopherol or intake of vitamin E
      (eight tocopherols and tocotrienols) was associated with prostate cancer risk
      with up to 19 years of follow-up in the alpha-Tocopherol, beta-Carotene Cancer
      Prevention Study cohort. Of the 29,133 Finnish male smokers, ages 50 to 69 years
      recruited into the study, 1,732 were diagnosed with incident prostate cancer
      between 1985 and 2004. Baseline serum alpha-tocopherol was measured by high
      performance liquid chromatography and the components of vitamin E intake were
      estimated based on a 276-item food frequency questionnaire and food chemistry
      analyses. Proportional hazard models were used to determine multivariate-adjusted
      relative risks (RR) and 95% confidence intervals (95% CI). Higher serum alpha
      tocopherol was associated with reduced risk of prostate cancer (RR, 0.80; 95% CI,
      0.66-0.96 for highest versus lowest quintile; Ptrend = 0.03) and was strongly and
      inversely related to the risk of developing advanced disease (RR, 0.56; 95% CI,
      0.36-0.85; Ptrend = 0.002). The inverse serum alpha-tocopherol-prostate cancer
      association was greater among those who were supplemented with either alpha
      tocopherol or beta-carotene during the trial. There were no associations between
      prostate cancer and the individual dietary tocopherols and tocotrienols. In
      summary, higher prediagnostic serum concentrations of alpha-tocopherol, but not
      dietary vitamin E, was associated with lower risk of developing prostate cancer,
      particularly advanced prostate cancer.

PMID- 17548694
TI  - A prospective cohort study of cancer incidence following the diagnosis of
      Parkinson's disease.
AB  - BACKGROUND: Prior studies suggest a decreased risk of cancer among patients with
      Parkinson's disease (PD). METHODS: Matched cohort analysis among the 22,071
      participants in the Physician's Health Study. A total of 487 incident cases of PD
      without preceding cancer were identified by self-report. Each PD case was matched
      by age to a reference participant who was alive and cancer free at the time of PD
      diagnosis. Both cohorts were followed for incident cancer. We used proportional
      hazards models to calculate adjusted relative risks (RR) for cancer. RESULTS: A
      total of 121 cancers were confirmed during a median follow-up of 5.2 years (PD)
      and 5.9 years (reference). Those with PD developed less cancer (11.0% versus
      14.0%), with an adjusted RR of 0.85 [95% confidence interval (95% CI), 0.59
      1.22]. Reduced risk was present for smoking-related cancers such as lung (RR,
      0.32), colorectal (RR, 0.54), and bladder (RR, 0.68), as well as for most non
      smoking-related cancers such as prostate cancer (RR, 0.74). In contrast, PD
      patients were at significantly increased risk (RR, 6.15; 95% CI, 1.77-21.37) for
      melanoma. PD patients who smoked were at reduced risk for smoking-related cancer
      (RR, 0.33; 95% CI, 0.12-0.92), whereas nonsmokers with PD were at increased risk
      (RR, 1.80; 95% CI, 0.60-5.39). This interaction was statistically significant
      (P(interaction) = 0.02). CONCLUSIONS: Our results suggest a decreased incidence
      of most cancers in patients with PD. PD patients had a significantly increased
      risk of malignant melanoma, a finding consistent with prior studies. We confirmed
      an interaction between smoking and the relationship of PD to smoking-related
      cancer that may fit the pattern of a gene-environment interaction.

PMID- 17548695
TI  - Risk of germ cell tumors among men with HIV/acquired immunodeficiency syndrome.
AB  - BACKGROUND: Men with HIV/acquired immunodeficiency syndrome (AIDS) are reported
      to be at increased risk for germ cell tumors (GCT), particularly testicular
      seminoma. We investigated correlates of this association to improve understanding
      of GCTs. METHODS: Testicular and extratesticular seminoma and nonseminoma cases
      were found by linking population-based cancer and HIV/AIDS registry data for
      268,950 men who developed AIDS in 1980 to 2003. Standardized incidence ratios
      (SIR) with 95% confidence intervals (95% CI) were used to compare these cases
      with the number of cases expected in the demographically matched population.
      RESULTS: Overall, seminoma risk (161 cases: SIR, 1.9; 95% CI, 1.6-2.2) was
      increased significantly with HIV/AIDS, whereas nonseminoma risk was not (56
      cases: SIR, 1.3; 95% CI, 0.96-1.7). Extratesticular GCT risk also was increased
      (11 cases: SIR, 2.1; 95% CI, 1.1-3.7). Seminoma risk was elevated regardless of
      age, race, or HIV/AIDS transmission group. It was highest for disseminated
      disease (SIR, 4.7; 95% CI, 2.9-7.2) and within 9 months of AIDS onset (SIR, 7.6;
      95% CI, 5.8-9.6), but it was unrelated to CD4 count and duration of HIV/AIDS. The
      excess risk of seminoma declined in more recent calendar periods, and it was no
      longer elevated (SIR, 1.4; 95% CI, 0.9-1.9) in the highly active antiretroviral
      treatment era. CONCLUSIONS: Men with HIV/AIDS had an increased risk of seminoma,
      but this risk may have attenuated with improving anti-HIV/AIDS treatments.
      Although detection bias could partly explain the excess of this cancer, various
      lines of evidence support a causal relationship. Possible mechanisms underlying
      this association include impaired tumor immunosurveillance or AIDS-related
      testicular atrophy.

PMID- 17548696
TI  - Arsenic metabolism, genetic susceptibility, and risk of premalignant skin lesions
      in Bangladesh.
AB  - We conducted a case-control study to investigate interindividual variability in
      susceptibility to health effects of inorganic arsenic due to arsenic metabolism
      efficiency, genetic factors, and their interaction. A total of 594 cases of
      arsenic-induced skin lesions and 1,041 controls was selected from baseline
      participants in a large prospective cohort study in Bangladesh. Adjusted odds
      ratios (OR) for skin lesions were estimated in relation to the polymorphisms in
      the glutathione S-transferase omega1 and methylenetetrahydrofolate reductase
      genes, the percentage of monomethylarsonous acid (%MMA) and dimethylarsinic acid
      (%DMA) in urine, and the ratios of MMA to inorganic arsenic and DMA to MMA. Water
      arsenic concentration was positively associated with %MMA and inversely
      associated with %DMA. The dose-response relationship of risk of skin lesion with
      %MMA was more apparent than those with other methylation indices; the ORs for
      skin lesions in relation to increasing %MMA quartiles were 1.00 (reference), 1.33
      [95% confidence interval (95% CI), 0.92-1.93], 1.68 (95% CI, 1.17-2.42), and 1.57
      (95% CI, 1.10-2.26; P for trend = 0.01). The ORs for skin lesions in relation to
      the methylenetetrahydrofolate reductase 677TT/1298AA and 677CT/1298AA diplotypes
      (compared with 677CC/1298CC diplotype) were 1.66 (95% CI, 1.00-2.77) and 1.77
      (95% CI, 0.61-5.14), respectively. The OR for skin lesions in relation to the
      glutathione S-transferase omega1 diplotype containing all at-risk alleles was
      3.91 (95% CI, 1.03-14.79). Analysis of joint effects of genotypes/diplotypes with
      water arsenic concentration and urinary %MMA suggests additivity of these
      factors. The findings suggest that arsenic metabolism, particularly the
      conversion of MMA to DMA, may be saturable and that differences in urinary
      arsenic metabolites, genetic factors related to arsenic metabolism, and their
      joint distributions modulate arsenic toxicity.

PMID- 17548697
TI  - Blood folate levels and risk of liver damage and hepatocellular carcinoma in a
      prospective high-risk cohort.
AB  - BACKGROUND: Studies in experimental animals suggest that low folate levels may
      play a role in liver damage and hepatocarcinogenesis. To examine this association
      in humans, folate levels in blood and risk for subsequent liver damage and
      hepatocellular carcinoma (HCC) were assessed in a population at high risk of
      liver cancer in China. METHODS: Four hundred fifteen hepatitis B surface antigen
      positive participants of the Haimen City Cohort were prospectively followed
      between 1998 and 2002. Serum and RBC folate levels were determined at baseline.
      Alanine aminotransferase (ALT) and hepatitis B virus DNA levels were measured
      semiannually. Logistic regression modeling was used to examine the presence of
      hepatitis B virus DNA and HCC, whereas linear regression with a log-link function
      was used to examine ALT levels. RESULTS: There was a statistically significant
      inverse association between serum folate level and ALT level. ALT levels
      decreased with each quartile increase in serum folate (adjusted odds ratio, 0.86;
      95% confidence interval, 0.76-0.97 for the highest compared with the lowest
      quartile; Ptrend = 0.002). After exclusion of three persons with prevalent HCC,
      20 (4.9%) of the 412 study participants developed HCC during follow-up, with a
      median time between enrollment and HCC diagnosis of 2.66 years (interquartile
      range, 1.8-4.1). When comparing persons in the lowest quartile RBC folate to
      persons in all other quartiles, the analysis found that higher RBC folate levels
      were associated with reduced risk of hepatocarcinogenesis (odds ratio, 0.33, 95%
      confidence interval, 0.13-0.86; P(trend) = 0.02). CONCLUSIONS: This study
      suggests that increased folate levels in humans may be inversely associated with
      the development of liver damage and HCC.

PMID- 17548698
TI  - Sun exposure and prostate cancer risk: evidence for a protective effect of early
      life exposure.
AB  - Mounting experimental and epidemiologic evidence supports the hypothesis that
      vitamin D reduces the risk of prostate cancer. Some evidence suggests that
      prostate cancer risk may be influenced by sun exposure early in life. We analyzed
      data from the National Health and Nutrition Examination Survey I Epidemiologic
      Follow-up Study to examine associations of prostate cancer risk with early-life
      and adult residential sun exposure and adult sun exposures that were assessed
      through self-report, physician report, and dermatologic examination. We used
      solar radiation in the state of birth as a measure of sun exposure in early life.
      Follow-up from 1971 to 1975 (baseline) to 1992 identified 161 prostate cancer
      cases (102 nonfatal and 59 fatal) among non-Hispanic white men for whom sun
      exposure data were available. Significant inverse associations were found for men
      born in a region of high solar radiation (relative risk, 0.49, 95% confidence
      interval, 0.27-0.90 for high versus low solar radiation), with a slightly greater
      reduction for fatal than for nonfatal prostate cancer. Frequent recreational sun
      exposure in adulthood was associated with a significantly reduced risk of fatal
      prostate cancer only (relative risk, 0.47; 95% confidence interval, 0.23-0.99).
      These findings suggest that, in addition to sun exposure in adulthood, sun
      exposure in early life protects against prostate cancer.

PMID- 17548699
TI  - Family history and the risk of kidney cancer: a multicenter case-control study in
      Central Europe.
AB  - An elevated familial relative risk may indicate either an important genetic
      component in etiology or shared environmental exposures within the family.
      Incidence rates of kidney cancer are particularly high in Central Europe,
      although no data were available on the familial aggregation or genetic background
      of kidney cancer in this region. We have, therefore, investigated the role of
      family history in first-degree relatives in a large multicenter case-control
      study in Central Europe. A total number of 1,097 cases of kidney cancer and 1,555
      controls were recruited from 2000 to 2003 from seven centers in Czech Republic,
      Poland, Romania, and Russia. The risk of kidney cancer increased with the
      increasing number of relatives with history of any cancer [odds ratio (OR), 1.15;
      95% confidence interval (95% CI), 1.00-1.31 per affected relative], and this
      association seemed to be more prominent among subjects with young onset (OR,
      1.55; 95% CI, 1.09-2.20 per affected relative). Overall, the OR was 1.40 (95% CI,
      0.71- 2.76) for the subjects who had at least one first-degree relative with
      kidney cancer after adjusting for tobacco smoking, body mass index, and medical
      history of hypertension, and this association was most apparent among subjects
      with affected siblings (OR, 4.09; 95% CI, 1.09-15.4). Based on the relative risk
      to siblings in our study population, we estimated that 80% of the kidney cancer
      cases are likely to occur in 20% of the population with the highest genetic risk,
      which indicate the importance of further investigation of genetic factors in
      cancer prevention for kidney cancer.

PMID- 17548700
TI  - Within-individual stability of obesity-related biomarkers among women.
AB  - OBJECTIVE: Novel biomarkers including proinflammatory cytokines and adipokines
      are being explored as potential mediators of cancer and other obesity-related
      conditions. Prospective studies linking biomarker levels with disease outcomes
      often measure biomarkers at a single time point and assume that the within
      individual variation in levels is small compared with the interindividual
      variation. However, this assumption is seldom tested. METHODS: This study
      examined the within-individual stability over time of plasma adiponectin,
      resistin, leptin, plasma activator inhibitor type 1, hepatocyte growth factor,
      tumor necrosis factor alpha, interleukin 6, and insulin among healthy young
      women. RESULTS: The study included 17 women (9 Black non-Hispanic, 2 Black
      Hispanic, 2 White Hispanic, and 4 other race/ethnicity) with mean age of 32.3
      years, mean body mass index of 31.2 kg/m2, and 76% prevalence of smoking.
      Analysis of intraclass correlation (ICC) suggested high to moderate correlation
      over repeated samples taken over 3 years in levels of resistin (ICC = 0.95),
      hepatocyte growth factor (0.91), plasma activator inhibitor type 1 (0.84),
      adiponectin (0.73), insulin (0.62), and leptin (0.58). ICCs were weaker for
      levels of proinflammatory cytokines, tumor necrosis factor alpha (0.39), and
      interleukin 6 (0.47). CONCLUSION: In this population of minority young females
      with a high prevalence of overweight and smoking, several obesity-related
      endocrine markers were stable over a period of 3 years. This supports the
      feasibility of longitudinal studies relating these biomarkers to the future
      occurrence of cancer and other health consequences of obesity.

PMID- 17548701
TI  - Association between germline variation in the FHIT gene and prostate cancer in
      Caucasians and African Americans.
AB  - Many studies have established that loss of heterozygosity and/or altered
      expression of the fragile histidine triad (FHIT) gene is a common event in a
      number of tumor types including prostate carcinoma. Encompassing the most active
      fragile site in the human genome, FRA3B, FHIT has become the model fragile site
      associated tumor suppressor gene. In a recent study, linkage and association
      between germline genetic variation in FHIT (specifically single nucleotide
      polymorphism rs760317) and prostate cancer were reported. We sought to confirm
      this finding in two independent samples: (a) a family-based sample of 817 men
      with (n = 434) and without (n = 383) prostate cancer from 323 Caucasian families,
      and (b) a community-based case-control sample of African American men with (n =
      133) and without (n = 342) prostate cancer. Using a family-based association
      test, rs760317 was associated with prostate cancer in Caucasians (P = 0.031),
      with a reduction in the risk of prostate cancer among carriers of the minor
      allele (odds ratio, 0.66; 95% confidence interval, 0.42-1.04; P = 0.074). African
      American carriers experienced a similar risk reduction (odds ratio, 0.63; 95%
      confidence interval, 0.42-0.96; P = 0.032). These results are remarkably
      consistent across ethnic samples but are in opposition to results from the
      original study, which showed an association between the minor allele of rs760317
      and an increased risk of prostate cancer. Taken together, the consistently
      significant but flipped association between single nucleotide polymorphism
      rs760317 and prostate cancer in three independent samples suggests that rs760317
      may be in linkage disequilibrium with one or more prostate cancer susceptibility
      variants in or near FHIT.

PMID- 17548702
TI  - A multifaceted intervention to increase cervical cancer screening among
      underserved Korean women.
AB  - OBJECTIVE: Despite the proven survival benefits associated with cervical cancer
      screening, use of the Pap test continues to be suboptimal in some population
      subgroups, such as among Korean-American women who face considerable barriers to
      screening. Therefore, we evaluated a multifaceted intervention that combined
      psychoeducational counseling with patient navigation to address both psychosocial
      and access barriers to screening. METHOD: Women (n = 102) were recruited from
      Korean community centers and assigned to the intervention or control condition.
      The intervention group received cervical cancer education and patient navigation
      delivered by bilingual Korean health educators. The control group received
      general health education, including information about cervical cancer and
      screening. Assessments were obtained at baseline and postintervention. Screening
      behavior was assessed at 6 months postintervention. RESULTS: At baseline, 17% of
      participants reported having had a Pap test in the previous year. At 6 months
      postintervention, 83% of women in the intervention group had obtained screening
      compared with 22% in the control group, chi2(1) = 41.22, P < 0.001. Multivariate
      logistic regression analyses indicated that participation in the intervention was
      associated with screening (P < 0.001). Fewer psychosocial barriers (e.g.,
      discomfort at having a stranger perform Pap) and greater self-efficacy were also
      associated with screening (P < 0.05). CONCLUSION: A combined modality
      intervention that delivers education with patient navigation training and
      assistance resulted in increased screening rates. Multifaceted approaches may be
      effective in reducing the psychosocial, access, and language barriers that
      contribute to cancer health disparities in underserved populations.

PMID- 17548703
TI  - Lack of association of transforming growth factor-beta1 polymorphisms and
      haplotypes with prostate cancer risk in the prostate, lung, colorectal, and
      ovarian trial.

PMID- 17548704
TI  - Dietary iron and heme iron intake and risk of breast cancer: a prospective cohort
      study.
AB  - Recent studies suggest that elevated body iron levels may contribute to breast
      carcinogenesis; however, epidemiologic evidence is lacking. We used data from a
      large cohort study of Canadian women to assess breast cancer in association with
      total iron and heme iron intake. Among 49,654 women ages 40 to 59 followed for an
      average of 16.4 years, we identified 2,545 incident breast cancer cases. Data
      from a food frequency questionnaire administered at baseline were used to
      calculate total dietary iron and heme iron intake. Using Cox proportional hazards
      models, we found no association of iron or heme iron intake with risk of breast
      cancer overall, in women consuming 30+ g of alcohol per day, or in women who had
      ever used hormone replacement therapy. The present study offers no support for an
      association of iron or heme iron intake with breast cancer risk or for a
      modification by iron of the effect of alcohol or estrogen. However, further
      cohort studies with repeated measurement of iron intake are warranted.

PMID- 17548705
TI  - MIC1 and IL1RN genetic variation and advanced prostate cancer risk.

PMID- 17548706
TI  - CYP2B6 genotype does not alter nicotine metabolism, plasma levels, or abstinence
      with nicotine replacement therapy.

PMID- 17548707
TI  - Insulin resistance-related gene polymorphisms and risk of prostate cancer.

PMID- 17548708
TI  - Lack of effect modification between estrogen metabolism genotypes and combined
      hormone replacement therapy in postmenopausal breast cancer risk.

PMID- 17548709
TI  - Abandon neither the food frequency questionnaire nor the dietary fat-breast
      cancer hypothesis.

PMID- 17548711
TI  - Antibiotics and breast cancer.

PMID- 17548713
TI  - Noninvasive input impedance of the human systemic circulation.

PMID- 17548715
TI  - Influence of siesta in the estimation of blood pressure control in patients with
      hypertension.

PMID- 17548716
TI  - Treating obstructive sleep apnea: is there more to the story than 2 millimeters
      of mercury?

PMID- 17548717
TI  - Does 20-hydroxyeicosatetraenoic acid contribute to sex differences in
      cardiovascular risk by increasing oxidative stress?

PMID- 17548718
TI  - Food omega-3 fatty acid intake of individuals (total, linolenic acid, long-chain)
      and their blood pressure: INTERMAP study.
AB  - Findings from short-term randomized trials indicate that dietary supplements of
      omega-3 polyunsaturated fatty acids (PFA) lower blood pressure of hypertensive
      persons, but effect size in nonhypertensive individuals is small and
      nonsignificant. Data are lacking on food omega-3 PFA and blood pressure in
      general populations. The International Study of Macro- and Micro-nutrients and
      Blood Pressure (INTERMAP) is an international cross-sectional epidemiologic study
      of 4680 men and women ages 40 to 59 from 17 population-based samples in China,
      Japan, United Kingdom, and United States. We report associations of food omega-3
      PFA intake (total, linolenic acid, long-chain) of individuals with blood
      pressure. Systolic and diastolic blood pressure were measured 8 times at 4
      visits. With several models to control for possible confounders (dietary, other),
      linear regression analyses showed inverse relationship of total omega-3 PFA from
      food (percent kilocalories, from four 24-hour dietary recalls) to systolic and
      diastolic blood pressures. With adjustment for 17 variables, estimated systolic
      blood pressure/diastolic blood pressure differences with 2 standard deviation
      higher (0.67% kcal) omega-3 PFA were -0.55/-0.57 mm Hg (Z-score -1.33, -2.00);
      for 2238 persons without medical or dietary intervention, -1.01/-0.98 mm Hg (Z 
      1.63, -2.25); for 2038 nonhypertensive persons from this sub-cohort, -0.91/-0.92
      mm Hg (Z -1.80, -2.38). For linolenic acid (largely from vegetable foods), blood
      pressure differences were similar, eg, for the 2238 "nonintervened" individuals, 
      0.97/-0.87 mm Hg (Z -1.52, -1.95); blood pressure differences were -0.32/-0.45 mm
      Hg for long-chain omega-3 PFA (largely from fish). In summary, food omega-3 PFA
      intake related inversely to blood pressure, including in nonhypertensive persons,
      with small estimated effect size. Food omega-3 PFA may contribute to prevention
      and control of adverse blood pressure levels.

PMID- 17548719
TI  - Prevention of erythropoietin-associated hypertension.
AB  - Hypertension is the most significant complication from treatment with
      erythropoietin (Epo). Can Epo-induced hypertension be eliminated? We examined
      systemic and local effects of our genetically engineered products, Epo-binding
      protein (Epo-bp) and anti-Epo-bp antibodies, on randomly assigned Sprague-Dawley
      rats at midnight, 4 am, 8 am, noon, 4 pm, and 8 pm. Blood pressure, hematocrit,
      and body weight were measured immediately before and after the completion of a 4
      week, twice-weekly course of Epo (50 U/kg), Epo-bp, anti-Epo-bp antibodies, or
      physiological saline injections. Epo treatment increased hematocrit markedly
      overall as compared with the saline, Epo-bp, and anti-Epo-bp antibody groups
      (0.616 versus 0.427, 0.439, and 0.441, respectively) and at each of the 6 test
      times (all P<0.0001). Epo-bp and anti-Epo-bp antibody treatment with Epo had
      almost no effect on the Epo-induced hematocrit increase (0.616 versus 0.580 or
      0.591, respectively). Circadian blood pressures for Epo versus saline, Epo-bp,
      and anti-Epo-bp antibody groups were 136.2+/-2.3 versus 116.2+/-1.7, 118.4+/-2.1,
      and 116.6+/-2.1 mm Hg, respectively (each P<0.0001). Significantly increased
      blood pressure was detected at noon, 4 pm, 8 pm, and midnight in Epo treatment.
      When Epo was given with Epo-bp or anti-Epo-bp antibodies, blood pressure was
      maintained at similar levels as in saline treatment (each P<0.0001) as compared
      with Epo treatment alone. Overall, body, brain, and heart weights were
      significantly lower in Epo treatment than those of other groups. Thus, Epo-bp and
      anti-Epo-bp antibodies eliminate Epo-induced hypertension without affecting
      hematocrit and blood volume.

PMID- 17548720
TI  - Effects of native and modified low-density lipoproteins on monocyte recruitment
      in atherosclerosis.

PMID- 17548721
TI  - Vascular cytochrome P450 4A expression and 20-hydroxyeicosatetraenoic acid
      synthesis contribute to endothelial dysfunction in androgen-induced hypertension.
AB  - Epidemiological evidence suggests a role for sex-dependent mechanisms in the
      pathophysiology of hypertension. It has been shown that 5alpha
      dihydrotestosterone (DHT) administration (56 mg/kg of body weight per day IP for
      14 days) increases blood pressure, cytochrome P450 4A expression, and 20
      hydroxyeicosatetraenoic acid synthesis in rats. We examined whether increased
      vascular 20-hydroxyeicosatetraenoic acid synthesis underlies endothelial
      dysfunction and hypertension in DHT-treated male Sprague-Dawley rats by using
      HET0016, a selective cytochrome P450 4A inhibitor. Coadministration of HET0016
      (10 mg/kg per day IP for 14 days) to DHT-treated rats markedly reduced DHT
      induced interlobar arterial production of 20-hydroxyeicosatetraenoic acid (14.3+/
      1.5 versus 1.5+/-0.5 ng/mg of protein per hour; P<0.05), superoxide anion (246+/
      47 versus 31+/-8 cpm/microg of protein), and the levels of gp91-phox, p47-phox,
      and 3-nitrosylated proteins. Moreover, the maximal relaxing response to
      acetylcholine in phenylephrine-preconstricted renal interlobar arteries from DHT
      treated rats (42.8+/-4.8%) significantly (P<0.05) increased in the presence of
      HET0016 (81.5+/-10.8%). Importantly, the administration of HET0016 negated DHT
      induced hypertension; systolic blood pressure was reduced from 146+/-2 mm Hg in
      DHT-treated rats to 130+/-1 mm Hg (P<0.05). The results strongly implicate
      vascular cytochrome P450 4A-derived 20-hydroxyeicosatetraenoic acid in the
      development of androgen-induced endothelial dysfunction and hypertension.

PMID- 17548722
TI  - Effect of nocturnal nasal continuous positive airway pressure on blood pressure
      in obstructive sleep apnea.
AB  - Obstructive sleep apnea (OSA) is a very common risk factor for hypertension, and
      continuous positive airway pressure (CPAP) has been widely used to treat OSA. We
      conducted a meta-analysis of randomized, controlled trials to evaluate the
      effects of CPAP on blood pressure, reported as either a primary or secondary end
      point, among patients with OSA. Studies were retrieved by searching Medline
      (January 1980 to July 2006), the Cochrane Database of Systematic Reviews,
      conference abstracts, and bibliographies of review and original articles. From
      255 relevant reports, 16 randomized clinical trials were selected that compared
      CPAP to control among participants with OSA, had a minimum treatment duration of
      2 weeks, and reported blood pressure changes during the intervention or control
      period. Data on sample size, participant characteristics, study design,
      intervention methods, duration, and treatment results were independently
      abstracted by 2 investigators using a standardized protocol. Data from 16 trials
      representing 818 participants were examined using a random-effects model. Mean
      net change in systolic blood pressure for those treated with CPAP compared with
      control was -2.46 mm Hg (95% CI: -4.31 to -0.62); mean net change in diastolic
      blood pressure was -1.83 mm Hg (95% CI: -3.05 to -0.61); and mean net change in
      mean arterial pressure was -2.22 mm Hg (95% CI: -4.38 to -0.05). Net reductions
      in blood pressure were not statistically different between daytime and nighttime.
      These results indicate that CPAP decreases blood pressure among those with OSA
      and may help prevent hypertension.

PMID- 17548723
TI  - Cerebrovascular function in pregnancy and eclampsia.

PMID- 17548724
TI  - Heritability, linkage, and genetic associations of exercise treadmill test
      responses.
AB  - BACKGROUND: The blood pressure (BP) and heart rate responses to exercise
      treadmill testing predict incidence of cardiovascular disease, but the genetic
      determinants of hemodynamic and chronotropic responses to exercise are largely
      unknown. METHODS AND RESULTS: We assessed systolic BP, diastolic BP, and heart
      rate during the second stage of the Bruce protocol and at the third minute of
      recovery in 2982 Framingham Offspring participants (mean age 43 years; 53%
      women). With use of residuals from multivariable models adjusted for clinical
      correlates of exercise treadmill testing responses, we estimated the heritability
      (variance-components methods), genetic linkage (multipoint quantitative trait
      analyses), and association with 235 single-nucleotide polymorphisms in 14
      candidate genes selected a priori from neurohormonal pathways for their potential
      role in exercise treadmill testing responses. Heritability estimates for heart
      rate during exercise and during recovery were 0.32 and 0.34, respectively.
      Heritability estimates for BP variables during exercise were 0.25 and 0.26
      (systolic and diastolic BP) and during recovery, 0.16 and 0.13 (systolic and
      diastolic BP), respectively. Suggestive linkage was found for systolic BP during
      recovery from exercise (locus 1q43-44, log-of-the-odds score 2.59) and diastolic
      BP during recovery from exercise (locus 4p15.3, log-of-the-odds score 2.37).
      Among 235 single-nucleotide polymorphisms tested for association with exercise
      treadmill testing responses, the minimum nominal probability value was 0.003,
      which was nonsignificant after adjustment for multiple testing. CONCLUSIONS:
      Hemodynamic and chronotropic responses to exercise are heritable and demonstrate
      suggestive linkage to select loci. Genetic mapping with newer approaches such as
      genome-wide association may yield novel insights into the physiological responses
      to exercise.

PMID- 17548725
TI  - Exercise training normalizes sympathetic outflow by central antioxidant
      mechanisms in rabbits with pacing-induced chronic heart failure.
AB  - BACKGROUND: In a recent study, we demonstrated that an increase in oxidative
      stress in the rostral ventrolateral medulla plays a critical role in the
      sympathoexcitation observed in chronic heart failure (CHF). Growing evidence
      indicates that exercise training evokes an antioxidative effect in CHF. In the
      present study, we therefore hypothesized that long-term exercise exerts its
      beneficial effect on autonomic activity in CHF via central antioxidative
      mechanisms. METHODS AND RESULTS: Experiments were performed on New Zealand White
      rabbits. All rabbits were instrumented to measure mean arterial pressure, heart
      rate, and renal sympathetic nerve activity and to test baroreflex sensitivity.
      Exercise training significantly decreased baseline renal sympathetic nerve
      activity (65.8+/-5.2% to 41.3+/-3.9% of Max [where "Max" is the maximum renal
      sympathetic nerve activity induced by a 50-mL puff of smoke directed to the
      external nares of the rabbit], P<0.05) and increased the maximal gain of the
      baroreflex curves for heart rate (2.2+/-0.2 to 4.6+/-0.7 bpm per mm Hg, P<0.01)
      and renal sympathetic nerve activity (1.9+/-0.2% to 4.5+/-0.4% of Max per mm Hg,
      P<0.01) in CHF rabbits. Exercise training increased expression of CuZn superoxide
      dismutase (0.3+/-0.1 to 1.5+/-0.3 [ratio of CuZn superoxide dismutase to
      tubulin], P<0.01) and decreased NAD(P)H oxidase subunit gp91(phox) protein
      expression (1.9+/-0.2 to 1.2+/-0.1 [ratio of gp91(phox) to tubulin], P<0.05) in
      the rostral ventrolateral medulla of CHF rabbits. Central overexpression of CuZn
      superoxide dismutase dose-dependently decreased baseline renal sympathetic nerve
      activity (control, 68.5+/-7.1% of Max; 10(10) particles of adenovirus, 53.2+/
      4.4% of Max; and 10(11) particles of adenovirus, 33.7+/-3.5% of Max; P<0.05) in
      CHF rabbits. CONCLUSIONS: These results suggest that an upregulation in central
      antioxidative mechanisms and suppressed central prooxidant mechanisms may
      contribute to the exercise training-induced beneficial effects on autonomic
      activity in CHF.

PMID- 17548726
TI  - Superior cardiovascular effect of aerobic interval training versus moderate
      continuous training in heart failure patients: a randomized study.
AB  - BACKGROUND: Exercise training reduces the symptoms of chronic heart failure.
      Which exercise intensity yields maximal beneficial adaptations is controversial.
      Furthermore, the incidence of chronic heart failure increases with advanced age;
      it has been reported that 88% and 49% of patients with a first diagnosis of
      chronic heart failure are >65 and >80 years old, respectively. Despite this, most
      previous studies have excluded patients with an age >70 years. Our objective was
      to compare training programs with moderate versus high exercise intensity with
      regard to variables associated with cardiovascular function and prognosis in
      patients with postinfarction heart failure. METHODS AND RESULTS: Twenty-seven
      patients with stable postinfarction heart failure who were undergoing optimal
      medical treatment, including beta-blockers and angiotensin-converting enzyme
      inhibitors (aged 75.5+/-11.1 years; left ventricular [LV] ejection fraction 29%;
      VO2peak 13 mL x kg(-1) x min(-1)) were randomized to either moderate continuous
      training (70% of highest measured heart rate, ie, peak heart rate) or aerobic
      interval training (95% of peak heart rate) 3 times per week for 12 weeks or to a
      control group that received standard advice regarding physical activity. VO2peak
      increased more with aerobic interval training than moderate continuous training
      (46% versus 14%, P<0.001) and was associated with reverse LV remodeling. LV end
      diastolic and end-systolic volumes declined with aerobic interval training only,
      by 18% and 25%, respectively; LV ejection fraction increased 35%, and pro-brain
      natriuretic peptide decreased 40%. Improvement in brachial artery flow-mediated
      dilation (endothelial function) was greater with aerobic interval training, and
      mitochondrial function in lateral vastus muscle increased with aerobic interval
      training only. The MacNew global score for quality of life in cardiovascular
      disease increased in both exercise groups. No changes occurred in the control
      group. CONCLUSIONS: Exercise intensity was an important factor for reversing LV
      remodeling and improving aerobic capacity, endothelial function, and quality of
      life in patients with postinfarction heart failure. These findings may have
      important implications for exercise training in rehabilitation programs and
      future studies.

PMID- 17548727
TI  - Tobacco smoke exposure is associated with attenuated endothelial function in 11
      year-old healthy children.
AB  - BACKGROUND: Passive smoking is associated with early arterial damage in adults,
      but its effect on endothelial function in children is unknown. METHODS AND
      RESULTS: Serum cotinine concentration was measured annually in children between 8
      and 11 years of age who had participated since infancy in a randomized,
      prospective atherosclerosis prevention trial (Special Turku Coronary Risk Factor
      Intervention Project for children [STRIP]). At age 11, endothelium-dependent flow
      mediated vasodilatory responses of the brachial artery were examined with high
      resolution ultrasound in 402 children. These children were divided into 3 groups
      according to serum cotinine concentrations: the noncotinine group (nondetectable
      cotinine, n=229), the low cotinine group (cotinine between 0.2 and 1.6 ng/mL,
      n=134), and the top decile cotinine group (cotinine > or = 1.7 ng/mL, n=39).
      Longitudinal cotinine data in children aged 8 to 11 years and ultrasound studies
      were available in 327 children. At age 11, the increase in cotinine concentration
      was associated with attenuated peak flow-mediated dilation response (mean+/-SD:
      the noncotinine group 9.10+/-3.88%, the low-cotinine group 8.57+/-3.78%, and the
      top-decile cotinine group 7.73+/-3.85%; P=0.03 for trend). Similarly, total
      dilation response (the area under the dilation response versus time curve between
      40 and 180 seconds after hyperemia) was affected by the cotinine level (P=0.02
      for trend). These trends were not explained by traditional atherosclerosis risk
      factors. Arterial measures and passive smoking showed even stronger associations
      when longitudinal cotinine data were used (peak flow-mediated dilation, P=0.01
      for trend; total dilation response, P=0.008 for trend). CONCLUSIONS: Exposure to
      environmental tobacco smoke confirmed by serum cotinine concentrations impairs
      endothelial function in a dose-dependent manner in 11-year-old children.

PMID- 17548728
TI  - Long-term prognostic value of neopterin: a novel marker of monocyte activation in
      patients with acute coronary syndrome.
AB  - BACKGROUND: Monocyte activation is believed to play an important role in the
      pathogenesis of acute coronary syndromes (ACS). Neopterin is a soluble marker of
      monocyte activation, and elevated levels are of prognostic value in patients with
      stable coronary artery disease. METHODS AND RESULTS: Neopterin levels were
      measured on average at 7 days (in 3946 patients) and at 4 months (in 3369
      patients) after ACS in the PRavastatin Or atorVastatin Evaluation Infection
      Therapy-Thrombolysis In Myocardial Infarction (PROVE IT-TIMI 22) trial. We
      assessed the relationship between plasma neopterin levels and the risk of death
      and death or acute coronary events (nonfatal myocardial infarction or unstable
      angina) over 2 years. Seven days after an ACS event, neopterin levels > or =
      12.11 nmol/L (upper quartile, derived from a post hoc analysis) were associated
      with an increased risk of death and an increased risk of death or acute coronary
      events after adjustment for age, gender, history of diabetes mellitus, history of
      hypertension, history of smoking, type of ACS presentation, use of percutaneous
      coronary intervention for the index event, statin regimen, low-density
      lipoprotein cholesterol, and high-sensitivity C-reactive protein (hazard ratio,
      1.86 [95% CI, 1.24 to 2.77], P=0.003; and hazard ratio, 1.33 [95% CI, 1.09 to
      1.63] P=0.006, respectively). Neopterin levels > or = 12.11 nmol/L at 4 months
      remained a predictor of death alone and of death or acute coronary events after
      multivariable adjustment that included adjustment for month 4 low-density
      lipoprotein cholesterol, high-sensitivity C-reactive protein, and statin regimen
      (hazard ratio, 2.39 [95% CI, 1.43 to 3.99], P=0.001; and hazard ratio, 1.60 [95%
      CI, 1.21 to 2.11], P=0.001). High-dose atorvastatin significantly attenuated the
      risk among subjects with neopterin levels > or = 12.11 nmol/L at baseline
      (interaction P for death or acute coronary event, 0.018). CONCLUSIONS: Increased
      monocyte activation detected by an elevated plasma neopterin level identifies
      patients at long-term risk of death or recurrent acute coronary events after ACS.
      Intensive statin therapy significantly attenuates the risk of recurrent events
      among patients with an elevated neopterin level.

PMID- 17548729
TI  - N-terminal pro-B-type natriuretic peptide testing improves the management of
      patients with suspected acute heart failure: primary results of the Canadian
      prospective randomized multicenter IMPROVE-CHF study.
AB  - BACKGROUND: The diagnostic utility of N-terminal pro-B-type natriuretic peptide
      (NT-proBNP) in heart failure has been documented. However, most of the data were
      derived from countries with high healthcare resource use, and randomized evidence
      for utility of NT-proBNP was lacking. METHODS AND RESULTS: We tested the
      hypothesis that NT-proBNP testing improves the management of patients presenting
      with dyspnea to emergency departments in Canada by prospectively comparing the
      clinical and economic impact of a randomized management strategy either guided by
      NT-proBNP results or without knowledge of NT-proBNP concentrations. Five hundred
      patients presenting with dyspnea to 7 emergency departments were studied. The
      median NT-proBNP level among the 230 subjects with a final diagnosis of heart
      failure was 3697 compared with 212 pg/mL in those without heart failure
      (P<0.00001). Knowledge of NT-proBNP results reduced the duration of ED visit by
      21% (6.3 to 5.6 hours; P=0.031), the number of patients rehospitalized over 60
      days by 35% (51 to 33; P=0.046), and direct medical costs of all ED visits,
      hospitalizations, and subsequent outpatient services (US $6129 to US $5180 per
      patient; P=0.023) over 60 days from enrollment. Adding NT-proBNP to clinical
      judgment enhanced the accuracy of a diagnosis; the area under the receiver
      operating characteristic curve increased from 0.83 to 0.90 (P<0.00001).
      CONCLUSIONS: In a universal health coverage system mandating judicious use of
      healthcare resources, inclusion of NT-proBNP testing improves the management of
      patients presenting to emergency departments with dyspnea through improved
      diagnosis, cost savings, and improvement in selected outcomes.

PMID- 17548730
TI  - Randomized trial of acupuncture to lower blood pressure.
AB  - BACKGROUND: Arterial hypertension is a prime cause of morbidity and mortality in
      the general population. Pharmacological treatment has limitations resulting from
      drug side effects, costs, and patient compliance. Thus, we investigated whether
      traditional Chinese medicine acupuncture is able to lower blood pressure. METHODS
      AND RESULTS: We randomized 160 outpatients (age, 58+/-8 years; 78 men) with
      uncomplicated arterial hypertension in a single-blind fashion to a 6-week course
      of active acupuncture or sham acupuncture (22 sessions of 30 minutes' duration).
      Seventy-eight percent were receiving antihypertensive medication, which remained
      unchanged. Primary outcome parameters were mean 24-hour ambulatory blood pressure
      levels after the treatment course and 3 and 6 months later. One hundred forty
      patients finished the treatment course (72 with active treatment, 68 with sham
      treatment). There was a significant (P<0.001) difference in posttreatment blood
      pressures adjusted for baseline values between the active and sham acupuncture
      groups at the end of treatment. For the primary outcome, the difference between
      treatment groups amounted to 6.4 mm Hg (95% CI, 3.5 to 9.2) and 3.7 mm Hg (95%
      CI, 1.6 to 5.8) for 24-hour systolic and diastolic blood pressures, respectively.
      In the active acupuncture group, mean 24-hour ambulatory systolic and diastolic
      blood pressures decreased significantly after treatment by 5.4 mm Hg (95% CI, 3.2
      to 7.6) and 3.0 mm Hg (95% CI, 1.5 to 4.6), respectively. At 3 and 6 months, mean
      systolic and diastolic blood pressures returned to pretreatment levels in the
      active treatment group. CONCLUSIONS: Acupuncture according to traditional Chinese
      medicine, but not sham acupuncture, after 6 weeks of treatment significantly
      lowered mean 24-hour ambulatory blood pressures; the effect disappeared after
      cessation of acupuncture treatment.

PMID- 17548731
TI  - Pilot randomized clinical trial of prehospital induction of mild hypothermia in
      out-of-hospital cardiac arrest patients with a rapid infusion of 4 degrees C
      normal saline.
AB  - BACKGROUND: Although delayed hospital cooling has been demonstrated to improve
      outcome after cardiac arrest, in-field cooling started immediately after the
      return of spontaneous circulation may be more beneficial. The aims of the present
      pilot study were to assess the feasibility, safety, and effectiveness of in-field
      cooling. METHODS AND RESULTS: We determined the effect on esophageal temperature,
      before hospital arrival, of infusing up to 2 L of 4 degrees C normal saline as
      soon as possible after resuscitation from out-of-hospital cardiac arrest. A total
      of 125 such patients were randomized to receive standard care with or without
      intravenous cooling. Of the 63 patients randomized to cooling, 49 (78%) received
      an infusion of 500 to 2000 mL of 4 degrees C normal saline before hospital
      arrival. These 63 patients experienced a mean temperature decrease of 1.24+/-1
      degrees C with a hospital arrival temperature of 34.7 degrees C, whereas the 62
      patients not randomized to cooling experienced a mean temperature increase of
      0.10+/-0.94 degrees C (P<0.0001) with a hospital arrival temperature of 35.7
      degrees C. In-field cooling was not associated with adverse consequences in terms
      of blood pressure, heart rate, arterial oxygenation, evidence for pulmonary edema
      on initial chest x-ray, or rearrest. Secondary end points of awakening and
      discharged alive from hospital trended toward improvement in ventricular
      fibrillation patients randomized to in-field cooling. CONCLUSIONS: These pilot
      data suggest that infusion of up to 2 L of 4 degrees C normal saline in the field
      is feasible, safe, and effective in lowering temperature. We propose that the
      effect of this cooling method on neurological outcome after cardiac arrest be
      studied in larger numbers of patients, especially those whose initial rhythm is
      ventricular fibrillation.

PMID- 17548732
TI  - Long-term progression and outcomes with aging in patients with lone atrial
      fibrillation: a 30-year follow-up study.
AB  - BACKGROUND: The long-term natural history of lone atrial fibrillation is unknown.
      Our objective was to determine the rate and predictors of progression from
      paroxysmal to permanent atrial fibrillation over 30 years and the long-term risk
      of heart failure, thromboembolism, and death compared with a control population.
      METHODS AND RESULTS: A previously characterized Olmsted County, Minnesota,
      population with first episode of documented atrial fibrillation between 1950 and
      1980 and no concomitant heart disease or hypertension was followed up long term.
      Of this unique cohort, 76 patients with paroxysmal (n=34), persistent (n=37), or
      permanent (n=5) lone atrial fibrillation at initial diagnosis met inclusion
      criteria (mean age at diagnosis, 44.2+/-11.7 years; male, 78%). Mean duration of
      follow-up was 25.2+/-9.5 years. Of 71 patients with paroxysmal or persistent
      atrial fibrillation, 22 had progression to permanent atrial fibrillation. Overall
      survival of the 76 patients with lone atrial fibrillation was 92% and 68% at 15
      and 30 years, respectively, similar to 86% and 57% survival for the age- and sex
      matched Minnesota population. Observed survival free of heart failure was
      slightly worse than expected (P=0.051). Risk for stroke or transient ischemic
      attack was similar to the expected population risk during the initial 25 years of
      follow-up but increased thereafter (P=0.004), although CIs were wide. All
      patients who had a cerebrovascular event had developed > or = 1 risk factor for
      thromboembolism. CONCLUSIONS: Comorbidities significantly modulate progression
      and complications of atrial fibrillation. Age or development of hypertension
      increases thromboembolic risk.

PMID- 17548733
TI  - Images in cardiovascular medicine. Conservative treatment of a left atrial
      hematoma and a localized tamponade occurring during treatment of coronary total
      occlusion.

PMID- 17548734
TI  - Images in cardiovascular medicine. Pacemaker implantation in a patient with
      dextrocardia, corrected transposition, and situs inversus.

PMID- 17548735
TI  - Images in cardiovascular medicine. Prominent crypt formation in the inferoseptum
      of a hypertrophic cardiomyopathy mutation carrier mimics noncompaction
      cardiomyopathy.

PMID- 17548736
TI  - Letter by Grover et al regarding article, "Percutaneous implantation of the
      CoreValve self-expanding valve prosthesis in high-risk patients with aortic valve
      disease: the Siegburg First-in-Man study".

PMID- 17548737
TI  - Pioneers of cardiology: Rune Elmqvist, MD.

PMID- 17548738
TI  - Valid comparisons of antifibrinolytic agents used in cardiac surgery.

PMID- 17548739
TI  - Heterotaxia, congenital heart disease, and primary ciliary dyskinesia.

PMID- 17548740
TI  - Women, acute ischemic heart disease, and antithrombotic therapy: challenges and
      opportunities.

PMID- 17548741
TI  - Aortic stenosis: two steps forward, one step back.

PMID- 17548742
TI  - Abdominal aortic aneurysm: the prognosis in women is worse than in men.

PMID- 17548743
TI  - Meta-analysis.

PMID- 17548744
TI  - Composition VI.

PMID- 17548745
TI  - Cognitive improvement in response to antipsychotic drugs: neurocognitive effects
      of antipsychotic medications in patients with chronic schizophrenia in the CATIE
      Trial.

PMID- 17548746
TI  - Neurocognitive effects of antipsychotic medications in patients with chronic
      schizophrenia in the CATIE Trial.
AB  - CONTEXT: Neurocognitive impairment in schizophrenia is severe and is an important
      predictor of functional outcome. The relative effect of the second-generation
      (atypical) antipsychotic drugs and older agents on neurocognition has not been
      comprehensively determined. OBJECTIVE: To compare the neurocognitive effects of
      several second-generation antipsychotics and a first-generation antipsychotic,
      perphenazine. DESIGN: Randomized, double-blind study of patients with
      schizophrenia assigned to receive treatment with olanzapine, perphenazine,
      quetiapine fumarate, or risperidone for up to 18 months as reported previously by
      Lieberman et al. Ziprasidone hydrochloride was included after its approval by the
      Food and Drug Administration. SETTING: Fifty-seven sites participated, including
      academic sites and treatment mental health facilities representative of the
      community. PATIENTS: From a cohort of 1460 patients in the treatment study, 817
      completed neurocognitive testing immediately prior to randomization and then
      after 2 months of treatment. MAIN OUTCOME MEASURES: The primary outcome was
      change in a neurocognitive composite score after 2 months of treatment. Secondary
      outcomes included neurocognitive composite score change at 6 months and 18 months
      after continued treatment and changes in neurocognitive domains. RESULTS: At 2
      months, treatment resulted in small neurocognitive improvements of z = 0.13 for
      olanzapine (P<.002), 0.25 for perphenazine (P<.001), 0.18 for quetiapine
      (P<.001), 0.26 for risperidone (P<.001), and 0.12 for ziprasidone (P<.06), with
      no significant differences between groups. Results at 6 months were similar.
      After 18 months of treatment, neurocognitive improvement was greater in the
      perphenazine group than in the olanzapine and risperidone groups. Neurocognitive
      improvement predicted longer time to treatment discontinuation, independently
      from symptom improvement, in patients treated with quetiapine or ziprasidone.
      CONCLUSIONS: After 2 months of antipsychotic treatment, all groups had a small
      but significant improvement in neurocognition. There were no differences between
      any pair of agents, including the typical drug perphenazine. These results differ
      from the majority of previous studies, and the possible reasons are discussed.

PMID- 17548748
TI  - Childhood and adulthood psychological ill health as predictors of midlife
      affective and anxiety disorders: the 1958 British Birth Cohort.
AB  - CONTEXT: Affective and anxiety disorders in early adulthood are associated with
      internalizing and externalizing disorders in childhood. Previous studies have not
      examined whether the risk associated with childhood psychological ill health
      persists for midlife psychological health. OBJECTIVES: To examine whether
      childhood and adulthood psychological health are associated with midlife
      affective and anxiety disorders and to examine sex differences in these
      associations. DESIGN: Data were gathered during a biomedical survey of the 1958
      British Birth Cohort, a 45-year longitudinal study of 98% of births in 1 week in
      1958. SETTING: General population sample in England, Scotland, and Wales.
      PARTICIPANTS: Analyses were based on 9297 participants, 54% of the surviving
      sample. MAIN OUTCOME MEASURE: Diagnoses according to the International
      Statistical Classification of Diseases, 10th Revision (ICD-10) at age 45 years
      for depressive episode and generalized anxiety disorder. RESULTS: Internalizing
      and externalizing disorders at ages 7, 11, and 16 years were associated with a
      1.5- to 2-fold increase in risk for midlife anxiety and affective disorder
      (P<.05), whereas psychological ill health at ages 23, 33, and 42 years was
      associated with a 2- to 7-fold increase in risk for midlife disorder (P<.05).
      Early-adulthood associations were significantly stronger for men (P<.05). Type
      and age at onset of childhood problems did not contribute to variations in the
      associations with midlife disorder. Risk for midlife disorder increased
      significantly with the cumulative number of adulthood reports of psychological
      ill health (P<.001). CONCLUSIONS: Childhood psychological health is an important
      independent distal factor in adulthood psychological health. Adulthood
      psychological health shows stronger associations with midlife disorders,
      indicating a poorer prognosis for adulthood than childhood psychological ill
      health. Men may be more susceptible than women to the effects of psychological
      ill health in early adulthood on midlife disorders. Targeting prevention,
      recognition, and treatment efforts in early adulthood, as well as in childhood
      and adolescence, may significantly reduce the burden of disease.

PMID- 17548747
TI  - Depression and generalized anxiety disorder: cumulative and sequential
      comorbidity in a birth cohort followed prospectively to age 32 years.
AB  - CONTEXT: The close association between generalized anxiety disorder (GAD) and
      major depressive disorder (MDD) prompts questions about how to characterize this
      association in future diagnostic systems. Most information about GAD-MDD
      comorbidity comes from patient samples and retrospective surveys. OBJECTIVE: To
      revisit the sequential and cumulative comorbidity between GAD and MDD using data
      from a prospective longitudinal cohort. DESIGN: Prospective longitudinal cohort
      study. SETTING: New Zealand. PARTICIPANTS: The representative 1972-1973 Dunedin
      birth cohort of 1037 members was followed up to age 32 years with 96% retention.
      MAIN OUTCOME MEASURES: Research diagnoses of anxiety and depression were made at
      ages 11, 13, 15, 18, 21, 26, and 32 years. Mental health services were reported
      on a life history calendar. RESULTS: Sequentially, anxiety began before or
      concurrently in 37% of depression cases, but depression began before or
      concurrently in 32% of anxiety cases. Cumulatively, 72% of lifetime anxiety cases
      had a history of depression, but 48% of lifetime depression cases had anxiety.
      During adulthood, 12% of the cohort had comorbid GAD + MDD, of whom 66% had
      recurrent MDD, 47% had recurrent GAD, 64% reported using mental health services,
      47% took psychiatric medication, 8% were hospitalized, and 11% attempted suicide.
      In this comorbid group, depression onset occurred first in one third of the
      participants, anxiety onset occurred first in one third, and depression and
      anxiety onset began concurrently in one third. CONCLUSIONS: Challenging the
      prevailing notion that generalized anxiety usually precedes depression and
      eventually develops into depression, these findings show that the reverse pattern
      occurs almost as often. The GAD-MDD relation is strong, suggesting that the
      disorders could be classified in 1 category of distress disorders. Their
      developmental relation seems more symmetrical than heretofore presumed,
      suggesting that MDD is not necessarily primary over GAD in diagnostic hierarchy.
      This prospective study suggests that the lifetime prevalence of GAD and MDD may
      be underestimated by retrospective surveys and that comorbid GAD + MDD
      constitutes a greater mental health burden than previously thought.

PMID- 17548749
TI  - Combined treatment with sertraline and liothyronine in major depression: a
      randomized, double-blind, placebo-controlled trial.
AB  - BACKGROUND: Antidepressant treatments that achieve a higher remission rate than
      those currently available are urgently needed. The thyroid hormone
      triiodothyronine may potentiate antidepressant effects. OBJECTIVE: To determine
      the antidepressant efficacy and safety of liothyronine sodium (triiodothyronine)
      when administered concurrently with the selective serotonin reuptake inhibitor
      sertraline hydrochloride to patients with major depressive disorder. DESIGN:
      Double-blind, randomized, 8-week, placebo-controlled trial. SETTING: Outpatient
      referral centers. PATIENTS: A total of 124 adult outpatients meeting unmodified
      DSM-IV criteria for major depressive disorder without psychotic features.
      INTERVENTIONS: Patients were randomized to receive sertraline hydrochloride (50
      mg/d for 1 week; 100 mg/d thereafter) plus liothyronine sodium (20-25 microg/d
      for 1 week; 40-50 microg/d thereafter) or sertraline plus placebo for 8 weeks.
      MAIN OUTCOME MEASURES: The primary outcome measure was categorical response to
      treatment (> or =50% decrease in scores on the 21-item Hamilton Rating Scale for
      Depression from baseline to study end point). Remission rate (final Hamilton
      Rating Scale for Depression score, < or =6) was a secondary outcome measure.
      RESULTS: Intent-to-treat Hamilton Rating Scale for Depression response rates were
      70% and 50% in the sertraline-liothyronine and sertraline-placebo groups,
      respectively (P = .02; odds ratio, 2.93; 95% confidence interval, 1.23-7.35);
      remission rates were 58% with sertraline-liothyronine and 38% with sertraline
      placebo (P = .02; odds ratio, 2.69; 95% confidence interval, 1.16-6.49). Baseline
      T(3) values were lower in patients treated with sertraline-liothyronine who had
      remissions than in those without remissions (t(48) = 3.36; P<.002). Among
      patients treated with sertraline-liothyronine, remission was associated with a
      significant decrease in serum thyrotropin values (F(1,73) = 4.00; P<.05). There
      were no significant effects of liothyronine supplementation on frequency of
      adverse effects. CONCLUSIONS: These results demonstrate enhancement of the
      antidepressant effect of sertraline by concurrent treatment with liothyronine
      without a significant increase in adverse effects. The antidepressant effect of
      liothyronine may be directly linked to thyroid function.

PMID- 17548750
TI  - Association between treatment-emergent suicidal ideation with citalopram and
      polymorphisms near cyclic adenosine monophosphate response element binding
      protein in the STAR*D study.
AB  - CONTEXT: A small subset of patients with depression exhibit new or worsening
      suicidal thoughts or behavior during short-term treatment with antidepressants.
      Because cyclic adenosine monophosphate response element binding (CREB) protein
      has been implicated in both antidepressant mechanisms and suicide, the CREB1 gene
      represents a gene that possibly influences the risk for treatment-emergent
      suicidality. OBJECTIVE: To examine polymorphisms that span CREB1, which was
      previously associated with anger expression in men with major depressive
      disorder, for association with new or worsening suicidality. DESIGN: Nested case
      control study derived from the Sequenced Treatment Alternatives to Relieve
      Depression (STAR*D) study, a multicenter, prospective, open, 12-week
      effectiveness trial from July 1, 2001, to September 30, 2006. SETTING: Outpatient
      primary care and psychiatric clinics. Patients Individuals with nonpsychotic
      major depressive disorder for whom DNA was available and who did not report
      suicidal ideation at study entry were subsequently treated with citalopram
      hydrobromide for up to 12 weeks. MAIN OUTCOME MEASURE: Emergent suicidal
      ideation, defined as a score of 2 or higher on any postbaseline visit for
      participants whose baseline score was 0 or 1 on the 16-item Quick Inventory of
      Depressive Symptomatology-Clinician Rated suicide item. RESULTS: Of 1447
      participants, 124 (8.6%) subsequently reported suicidality on at least 1 visit;
      these individuals were compared with the remaining 1324 participants. Of 5 single
      nucleotide polymorphisms (SNPs) examined, none were significantly associated with
      treatment-emergent suicidality overall. However, 2 SNPs revealed a gene-by-sex
      interaction with suicidality. Among the 539 men, these 2 SNPs and 2 of the 5 SNP
      haplotypes were significantly associated with new-onset suicidality. CONCLUSIONS:
      Polymorphisms that span CREB1 were associated with treatment-emergent suicidality
      among men with depression, extending an observation of association with male
      anger expression in a prior independent cohort. If replicated, this finding would
      suggest that pharmacogenetic testing could facilitate the identification of the
      small subset of individuals at greater risk during short-term antidepressant
      treatment.

PMID- 17548751
TI  - Reading affect in the face and voice: neural correlates of interpreting
      communicative intent in children and adolescents with autism spectrum disorders.
AB  - CONTEXT: Understanding a speaker's communicative intent in everyday interactions
      is likely to draw on cues such as facial expression and tone of voice. Prior
      research has shown that individuals with autism spectrum disorders (ASD) show
      reduced activity in brain regions that respond selectively to the face and voice.
      However, there is also evidence that activity in key regions can be increased if
      task demands allow for explicit processing of emotion. OBJECTIVES: To examine the
      neural circuitry underlying impairments in interpreting communicative intentions
      in ASD using irony comprehension as a test case, and to determine whether
      explicit instructions to attend to facial expression and tone of voice will
      elicit more normative patterns of brain activity. DESIGN, SETTING, AND
      PARTICIPANTS: Eighteen boys with ASD (aged 7-17 years, full-scale IQ >70) and 18
      typically developing (TD) boys underwent functional magnetic resonance imaging at
      the Ahmanson-Lovelace Brain Mapping Center, University of California, Los
      Angeles. MAIN OUTCOME MEASURES: Blood oxygenation level-dependent brain activity
      during the presentation of short scenarios involving irony. Behavioral
      performance (accuracy and response time) was also recorded. RESULTS: Reduced
      activity in the medial prefrontal cortex and right superior temporal gyrus was
      observed in children with ASD relative to TD children during the perception of
      potentially ironic vs control scenarios. Importantly, a significant group x
      condition interaction in the medial prefrontal cortex showed that activity was
      modulated by explicit instructions to attend to facial expression and tone of
      voice only in the ASD group. Finally, medial prefrontal cortex activity was
      inversely related to symptom severity in children with ASD such that children
      with greater social impairment showed less activity in this region. CONCLUSIONS:
      Explicit instructions to attend to facial expression and tone of voice can elicit
      increased activity in the medial prefrontal cortex, part of a network important
      for understanding the intentions of others, in children with ASD. These findings
      suggest a strategy for future intervention research.

PMID- 17548752
TI  - Cerebral cortical gray matter overgrowth and functional variation of the
      serotonin transporter gene in autism.
AB  - CONTEXT: Autism is a heritable neurodevelopmental disorder characterized
      biologically by enlargement of the head and brain and abnormalities of serotonin
      neurotransmission. OBJECTIVE: To evaluate whether 5-HTTLPR, a functional promoter
      polymorphism of the serotonin transporter gene SLC6A4, influences cerebral
      cortical structure volumes in young male children with autism. DESIGN:
      Association study of a genetic variant with quantitative traits. SETTING: Autism
      research centers at the University of North Carolina (UNC), Chapel Hill, and the
      University of Washington (UW), Seattle. PARTICIPANTS: Forty-four male children, 2
      to 4 years old, with autism participating in longitudinal brain magnetic
      resonance imaging studies. MAIN OUTCOME MEASURES: Cerebral cortical and
      cerebellar gray and white matter volumes. RESULTS: We found that 5-HTTLPR
      genotype influenced gray matter volumes of the cerebral cortex (F(2,23) = 7.29, P
      = .004) and of 3 lobe-based subregions in the UNC sample of 29 children (frontal
      lobe gray matter: F(2,23) = 6.36, P = .01). The 5-HTTLPR short allele appeared to
      be additively associated with increasing gray matter volumes, an observation
      affirmed by tests of linear genotype effects (cortical gray matter: F(1,24) =
      14.11, P = .001; frontal lobe gray matter: F(1,24) = 13.20, P = .001). Genotype
      did not influence cerebellar volumes. Confirmation was pursued by means of the UW
      sample of 15 children. While effects were not significant in the UW sample alone,
      the patterns of adjusted means resembled those found in the UNC sample. Positive
      Cochran-Mantel-Haenszel test results supported the concordance of relationships
      across the 2 sites, and analyses of covariance of the combined sample that
      included a site covariate showed significant linear genotype effects on structure
      volumes (cortical gray matter: F(1,38) = 5.73, P = .02; frontal lobe gray matter:
      F(1,38) = 11.73, P = .002). Effect sizes of 5-HTTLPR genotype on total cortical
      and frontal lobe gray matter volumes were 10% and 16%, respectively. CONCLUSION:
      The SLC6A4 promoter polymorphism 5-HTTLPR influences cerebral cortical gray
      matter volumes in young male children with autism.

PMID- 17548753
TI  - Levels of beta-secretase (BACE1) in cerebrospinal fluid as a predictor of risk in
      mild cognitive impairment.
AB  - CONTEXT: Elevated beta-secretase (beta-site amyloid precursor protein-cleaving
      enzyme 1 [BACE1]) activity has been found in the brains of patients with sporadic
      Alzheimer disease (AD) compared with controls. Now we are particularly interested
      in whether BACE1 can be identified in the cerebrospinal fluid (CSF) of patients
      with mild cognitive impairment (MCI), a population at high risk for AD. The
      possible presence of BACE1 in the CSF of patients with AD and MCI has so far gone
      unreported. OBJECTIVE: To examine whether BACE1 can be identified in the CSF of
      patients with MCI. DESIGN: We evaluated CSF BACE1 levels using 2 sandwich enzyme
      linked immunosorbent assays, BACE1 enzymatic activities by means of synthetic
      fluorescence substrate, and total amyloid-beta peptide levels using a sandwich
      enzyme-linked immunosorbent assay. SETTING: Two independent research centers.
      PARTICIPANTS: Eighty patients with sporadic AD, 59 patients with MCI, and 69
      controls. MAIN OUTCOME MEASURES: BACE1 levels and enzymatic activities and
      amyloid-beta peptide levels. RESULTS: Increased CSF levels of BACE1 protein were
      associated with increased risk ratios (RRs) for patients with MCI compared with
      controls (RR, 2.08; 95% confidence interval [CI], 1.58-2.58) and patients with AD
      (RR, 1.65; 95% CI, 1.19-2.03). Similarly, patients with MCI showed increased
      levels of BACE1 activity compared with controls (RR, 2.17; 95% CI, 1.66-2.71) and
      patients with AD (RR, 3.71; 95% CI, 2.74-4.36). For total amyloid-beta peptide
      and tau, increased CSF levels were associated with a higher risk of MCI compared
      with controls. The BACE1 activity was significantly correlated with BACE1 protein
      level (rho = 0.23; P<.001) and amyloid-beta peptide level (rho = 0.39; P<.001),
      with amyloid-beta peptide correlated with BACE1 protein level (rho = 0.30;
      P<.001). CONCLUSION: Significant elevation of BACE1 levels and activity in CSF is
      an indicator of MCI, which could be an early stage of AD.

PMID- 17548754
TI  - Cognition in novice ecstasy users with minimal exposure to other drugs: a
      prospective cohort study.
AB  - CONTEXT: Ecstasy (street name for [+/-]-3,4-methylenedioxymethamphetamine [MDMA])
      use has been associated with cognitive deficits, especially in verbal memory.
      However, owing to the cross-sectional and retrospective nature of currently
      available studies, questions remain regarding the causal direction and clinical
      relevance of these findings. OBJECTIVE: To examine the relationship between
      Ecstasy use and subsequent cognitive performance. DESIGN: A prospective cohort
      study in Ecstasy-naive subjects with a high risk for future first Ecstasy use, as
      part of the Netherlands XTC Toxicity study. The initial examination took place
      between April 10, 2002, and April 28, 2004; follow-up was within 3 years after
      the initial examination. SETTING AND PARTICIPANTS: One hundred eighty-eight
      healthy Ecstasy-naive volunteers (mean age, 22 years) were recruited. Of these,
      58 subjects started using Ecstasy (mean cumulative dose, 3.2 tablets; median
      cumulative dose, 1.5 tablets). They were compared with 60 persistent Ecstasy
      naive subjects matched on age, sex, intelligence, and use of substances other
      than Ecstasy. Differences in cognition between Ecstasy users and Ecstasy-naive
      subjects were adjusted for differences in cannabis and other recreational drug
      use. MAIN OUTCOME MEASURES: Change scores between the initial examination and
      follow-up on neurocognitive tests measuring attention, working memory, verbal and
      visual memory, and visuospatial ability. RESULTS: At the initial examination,
      there were no statistically significant differences in any of the
      neuropsychological test scores between persistent Ecstasy-naive subjects and
      future Ecstasy users. However, at follow-up, change scores on immediate and
      delayed verbal recall and verbal recognition were significantly lower in the
      group of incident Ecstasy users compared with persistent Ecstasy-naive subjects.
      There were no significant differences on other test scores. CONCLUSIONS: Our
      findings suggest that even a first low cumulative dose of Ecstasy is associated
      with decline in verbal memory. Although the performance of the group of incident
      Ecstasy users is still within the normal range and the immediate clinical
      relevance of the observed deficits is limited, long-term negative consequences
      cannot be excluded.

PMID- 17548755
TI  - Brain pathology in pedophilic offenders: evidence of volume reduction in the
      right amygdala and related diencephalic structures.
AB  - CONTEXT: Pedophilic crime causes considerable public concern, but no causative
      factor of pedophilia has yet been pinpointed. In the past, etiological theories
      postulated a major impact of the environment, but recent studies increasingly
      emphasize the role of neurobiological factors, as well. However, the role of
      alterations in brain structures that are crucial in the development of sexual
      behavior has not yet been systematically studied in pedophilic subjects.
      OBJECTIVE: To examine whether pedophilic perpetrators show structural neuronal
      deficits in brain regions that are critical for sexual behavior and how these
      deficits relate to criminological characteristics. DESIGN: Amygdalar volume and
      gray matter of related structures that are critical for sexual development were
      compared in 15 nonviolent male pedophilic perpetrators (forensic inpatients) and
      15 controls using complementary morphometric analyses (voxel-based morphometry
      and volumetry). Psychosocial adjustment and sexual offenses were also assessed.
      RESULTS: Pedophilic perpetrators showed a significant decrease of right amygdalar
      volume, compared with healthy controls (P = .001). We observed reduced gray
      matter in the right amygdala, hypothalamus (bilaterally), septal regions,
      substantia innominata, and bed nucleus of the striae terminalis. In 8 of the 15
      perpetrators, enlargement of the anterior temporal horn of the right lateral
      ventricle that adjoins the amygdala could be recognized by routine qualitative
      clinical assessment. Smaller right amygdalar volumes were correlated with the
      propensity to commit uniform pedophilic sexual offenses exclusively (P = .006)
      but not with age (P = .89). CONCLUSIONS: Pedophilic perpetrators show structural
      impairments of brain regions critical for sexual development. These impairments
      are not related to age, and their extent predicts how focused the scope of sexual
      offenses is on uniform pedophilic activity. Subtle defects of the right amygdala
      and closely related structures might be implicated in the pathogenesis of
      pedophilia and might possibly reflect developmental disturbances or environmental
      insults at critical periods.

PMID- 17548756
TI  - On determining sensitivity to pain in borderline personality disorder.

PMID- 17548757
TI  - Dating violence, sexual assault, and suicide attempts among urban teenagers.
AB  - OBJECTIVE: To evaluate the relationship between dating violence, sexual assault,
      and suicide attempts among urban adolescents. DESIGN: Secondary analysis of the
      2005 New York City Youth Risk Behavior Survey. SETTING: Eighty-seven New York
      City public high schools. PARTICIPANTS: Representative population-based sample of
      8080 students, 14 years and older. MAIN EXPOSURES: Dating violence in the past
      year and lifetime history of sexual assault. OUTCOME MEASURE: One or more suicide
      attempts in the past year. RESULTS: Respondents were 50.0% female and primarily
      black (36.0%) or Hispanic (40.1%). In the past year, 11.7% of females and 7.2% of
      males reported 1 or more suicide attempts. Lifetime history of sexual assault was
      reported by 9.6% of females and 5.4% of males. Dating violence in the past year
      was reported by 10.6% of females and 9.5% of males. In multivariate models,
      controlling for persistent sadness, sexual orientation, and significant risk
      behaviors, recent dating violence (odds ratio, 1.61; 95% confidence interval,
      1.05-2.47) was associated with suicide attempts in adolescent girls, while
      lifetime history of sexual assault (odds ratio, 3.86; 95% confidence interval,
      2.11-7.06) was associated with suicide attempts in adolescent boys. CONCLUSIONS:
      In this population of urban youth, recent dating violence among females and
      lifetime history of sexual assault among males were significantly associated with
      suicide attempts. Clinicians and educators should be trained to routinely screen
      adolescents for violence victimization and should have a low threshold for
      referring these at-risk teenagers for mental health services.

PMID- 17548758
TI  - Childhood bullies and victims and their risk of criminality in late adolescence:
      the Finnish From a Boy to a Man study.
AB  - OBJECTIVE: To study correlations of childhood bullying and victimization with
      juvenile criminality. DESIGN: Longitudinal birth cohort study from age 8 years to
      ages 16 to 20 years. SETTING: Population-based study from Finland. PARTICIPANTS:
      The sample comprised 2551 boys (86.6% of the original birth cohort) with complete
      information about bullying and victimization from parents, teachers, and children
      at age 8 years. MAIN OUTCOME MEASURE: Information about criminal offenses from
      the National Police Register at ages 16 to 20 years. RESULTS: Frequent bullies
      and those who frequently both bullied and were bullied (8.8% of the sample) were
      responsible for 33.0% of all juvenile crimes during the 4-year study period.
      Frequent bully-only status predicted both occasional and repeated offending,
      whereas bully-victim status predicted repeated offending. Bullying predicted most
      types of crime (violence, property, drunk driving, and traffic offenses) when
      controlled with parental education level. However, frequent bullies or victims
      without a high level of psychiatric symptoms were not at an elevated risk for
      later criminality. CONCLUSIONS: Boys who frequently bully are at risk for later
      criminality when this condition is accompanied by a high level of psychiatric
      symptoms. Frequent bullies should be actively screened for psychiatric problems.

PMID- 17548759
TI  - Exposure to food advertising on television among US children.
AB  - OBJECTIVE: To examine exposure to food advertising on television (TV) among
      children aged 2 through 11 years. DESIGN: Weighted examination of the
      distribution of national advertisements (ads) using TV ratings data. SETTING:
      National ads from 170 top-rated TV shows viewed by children aged 2 through 11
      years from September 1, 2003, through May 31, 2004. PARTICIPANTS: Sample of
      224,083 ads. MAIN OUTCOME MEASURES: Television nonprogram content time was
      assessed across 6 mutually exclusive categories that included food products, non
      fast food restaurants, fast food restaurants, other products, public service
      announcements, and TV promotions. Food advertising was assessed according to 7
      food categories--cereal, snacks, sweets, beverages, fast food restaurants, non
      fast food restaurants, and other food products--and then examined across more
      detailed categories. RESULTS: In 2003-2004, 27.2% and 36.4% of children's
      exposure to total nonprogram content time and product advertising, respectively,
      was for food-related products. Similar distributions were found by race. Cereal
      was the most frequently seen food product, making up 27.6% of all food ads.
      Comparisons with previous studies suggest that, over time, food ads account for a
      smaller share of the product ads seen by US children. CONCLUSIONS: Children aged
      2 through 11 years are exposed to a substantial amount of food advertising
      through TV, but the dramatic increase in childhood obesity rates during the past
      few decades was not mirrored by similar changes in food advertising exposure.
      However, we found evidence of a very recent (2000-2005) upward trend in the
      amount of exposure to food advertising on TV among US children.

PMID- 17548760
TI  - School-based fitness changes are lost during the summer vacation.
AB  - OBJECTIVE: To determine the changes in percentage of body fat, cardiovascular
      fitness, and insulin levels during the 3-month summer break in overweight
      children enrolled in a school-based fitness program. STUDY DESIGN: Overweight
      middle-school children were randomized to a lifestyle-focused physical education
      class (treatment) or standard physical education class (control) for 1 school
      year (9 months; previously reported). This analysis reports changes during the 3
      month summer break in children who participated in the fitness intervention group
      and who remained at this school the following year and repeated a fitness class.
      At the beginning and end of the school year, children underwent evaluation of (1)
      fasting levels of insulin and glucose, (2) body composition by means of dual x
      ray absorptiometry, and (3) maximum oxygen consumption as determined by treadmill
      use. SETTING: Rural middle school and an academic children's hospital.
      PARTICIPANTS: Overweight middle-school children. INTERVENTION: School-based
      fitness curriculum, followed by summer break, and an additional year of school
      based fitness intervention. MAIN OUTCOME MEASURES: Cardiovascular fitness test
      results (maximum oxygen consumption), body composition, and fasting insulin
      levels. RESULTS: Improvements seen during the 9-month school-year intervention in
      cardiovascular fitness, fasting insulin levels, and body composition were lost
      during the 3-month summer break. During this summer break, mean +/- SD fitness
      level decreased (maximum oxygen consumption, -3.2 +/- 1.9 mL/kg per minute; P =
      .007), fasting insulin level increased (+44 +/- 69 pmol/L [+6.1 +/- 9.7 mIU/mL];
      P = .056), and percentage of body fat increased (+1.3% +/- 1.3%; P = .02) to
      levels that were similar to those seen before the school intervention.
      CONCLUSION: In obese middle-school children, school-based fitness interventions
      are an important vehicle for health promotion, but without sustained
      intervention, these benefits may be lost during the extended summer break.

PMID- 17548761
TI  - Short-term effects of school-based weight gain prevention among adolescents.
AB  - OBJECTIVE: To determine whether a multicomponent health promotion intervention
      for Dutch adolescents would be successful in influencing body composition and
      aerobic fitness. DESIGN: Randomized controlled trial. SETTING: Ten intervention
      and 8 control prevocational secondary schools. PARTICIPANTS: A total of 978
      adolescents (mean age, 12.7 years). INTERVENTION: An interdisciplinary
      multicomponent intervention program with an adapted curriculum for 11 biology and
      physical education lessons and environmental change options, including additional
      lessons on physical education and advice on the school canteen selection. MAIN
      OUTCOME MEASURES: Body height and weight, hip and waist circumference, 4 skinfold
      thickness measurements, and aerobic fitness. RESULTS: Multilevel analyses showed
      significant differences in changes after the 8-month intervention period in favor
      of the intervention group with regard to hip circumference (mean difference, 0.53
      cm; 95% confidence interval, 0.07 to 0.98) and sum of skinfolds among girls (mean
      difference, -2.31 mm; 95% confidence interval, -4.34 to -0.28). In boys, the
      intervention resulted in a significant difference in waist circumference (mean
      difference, -0.57 cm; 95% confidence interval, -1.10 to -0.05). No significant
      intervention effects were found related to aerobic fitness. CONCLUSIONS: The
      multicomponent Dutch Obesity Intervention in Teenagers program positively
      influenced several measures of body composition among both girls and boys. Our
      results indicate that secondary prevocational school curriculum changes may
      contribute to excessive weight gain prevention among adolescents.

PMID- 17548762
TI  - Cross-sectional study of female students reporting anabolic steroid use.
AB  - OBJECTIVE: To determine the characteristics of female US high school students
      reporting anabolic steroid use. DESIGN: Cross-sectional assessment using the 2003
      Centers for Disease Control and Prevention national school-based Youth Risk
      Behavior Survey database. SETTING: Nationally representative sample of US high
      schools. PARTICIPANTS: Female students in grades 9 through 12 (n = 7544). MAIN
      OUTCOME MEASURES: Participants' self-reported anabolic steroid use was compared
      with other health-related behaviors and with sports participation. RESULTS: Prior
      or ongoing anabolic steroid use was reported by 5.3% of female high school
      students. Those adolescent girls had a marked increase in other health
      compromising behaviors, including past 30-day use of alcohol (odds ratio [OR],
      8.83; 95% confidence interval [CI], 5.49-14.20]), cigarettes (OR, 5.14; 95% CI,
      3.14-8.42), marijuana (OR, 7.91; 95% CI, 5.20-12.04), cocaine (OR, 10.78; 95% CI,
      6.18-18.81), and diet pills (OR, 4.86; 95% CI, 2.98-7.93). They were more likely
      to carry a weapon (OR, 7.54; 95% CI, 4.83-11.76), have had sexual intercourse
      before age 13 years (OR, 2.90; 95% CI, 1.58-5.33), and have had feelings of
      sadness or hopelessness almost every day for at least 2 consecutive weeks (OR,
      4.13; 95% CI, 2.57-7.22). They were less likely to play school-sponsored team
      sports (OR, 0.52; 95% CI 0.34-0.80). Steroid users participating in sports shared
      the same problem behaviors as steroid users not participating in team athletics.
      CONCLUSION: Self-reported anabolic steroid use is not confined to adolescent
      girls in competitive athletics and is an indicator of adolescent girls with a
      marked increase in a cluster of other health-harming behaviors.

PMID- 17548763
TI  - Caregivers' responses to pain in their children in the emergency department.
AB  - OBJECTIVE: To explore physiological and anxiety responses of caregivers who
      witness a venipuncture being performed on their child and the effects of
      caregivers' responses on child pain and distress. DESIGN: Observational study
      between March 13, 2006, and June 8, 2006. SETTING: Tertiary-level pediatric
      emergency department in Toronto, Ontario. PARTICIPANTS: Fifty-five caregivers of
      children aged 1 month to 18 years. MAIN EXPOSURE: Observing a child receive an
      intravenous cannulation. OUTCOME MEASURES: The caregiver's heart rate, blood
      pressure, and anxiety (measured using a 10-cm visual analogue scale). Child
      caregiver interactions were measured using the Child-Adult Medical Procedure
      Interaction Scale-Short Form (child age, > or = 2 years) or the Measure of Adult
      and Infant Soothing and Distress (child age, < 2 years). Child pain was measured
      using the Faces Pain Scale-Revised. RESULTS: During cannulation, there was a
      significant increase in a caregiver's heart rate (median maximum difference = 12
      beats per minute; P<.001) and anxiety (median difference = 2.65 cm; P<.001). Mean
      arterial pressure decreased after cannulation (median difference = 4.4 mm Hg; P =
      .004). Backward linear regression revealed that 34% of the variability in child
      cannulation pain was predicted by caregiver anxiety and caregiver distress
      promoting behavior; 31% of the variability in a child's distress during
      cannulation was predicted by caregiver distress-promoting behavior. Caregiver
      heart rate and anxiety during cannulation and caregiver distress-promoting
      behavior during recovery accounted for 51% of the variability in the child's
      distress during recovery. CONCLUSIONS: Caregivers witnessing an intravenous
      cannulation in their child had elevated heart rate, blood pressure, and anxiety.
      These responses predicted child pain and distress. Future studies should evaluate
      interventions designed to decrease distress responses in caregivers.

PMID- 17548764
TI  - Neurodevelopmental outcomes of very low-birth-weight infants with necrotizing
      enterocolitis: a systematic review of observational studies.
AB  - OBJECTIVE: To systematically review observational studies reporting long-term
      neurodevelopmental outcomes in very low-birth-weight neonates surviving after
      necrotizing enterocolitis (NEC). DATA SOURCES: The Cochrane Central Register of
      Controlled Trials, MEDLINE, EMBASE, CINAHL (Cumulative Index to Nursing and
      Allied Health), and proceedings of the Pediatric Academic Societies (published in
      Pediatric Research since 1970) were searched in June and September 2006. The
      reference lists of identified studies and personal files were searched. STUDY
      SELECTION: All studies with a control group were eligible for inclusion. MAIN
      OUTCOME EXPOSURE: Necrotizing enterocolitis (stage II or higher) vs no NEC. MAIN
      OUTCOME MEASURE: Neurodevelopmental impairment at 1 year or older of corrected
      age. RESULTS: Eleven nonrandomized studies, including 5 with "matched controls,"
      were included in the analyses. The risk of long-term neurodevelopmental
      impairment was significantly higher in the presence of at least stage II NEC vs
      no NEC (odds ratio, 1.82; 95% confidence interval, 1.46-2.27). Significant
      heterogeneity (I2 = 47.9%; P = .06) between the studies indicated variations in
      patient, illness, and intervention characteristics and in follow-up methods.
      Patients with NEC requiring surgery were at higher risk for neurodevelopmental
      impairment vs those managed medically (odds ratio, 1.99; 95% confidence interval,
      1.26-3.14). Results of analyses based on study design, follow-up rate, and year
      of birth were not statistically significantly different from those of the overall
      analysis. Risk of cerebral palsy and cognitive and severe visual impairment was
      significantly higher in neonates with NEC. CONCLUSION: Survivors of stage II or
      higher NEC are at risk for long-term neurodevelopmental impairment, especially if
      they require surgery for the illness.

PMID- 17548765
TI  - Methamphetamine and young men who have sex with men: understanding patterns and
      correlates of use and the association with HIV-related sexual risk.
AB  - OBJECTIVE: To examine patterns, consequences, and correlates of methamphetamine
      use among adolescent and young adult men who have sex with men (YMSM). DESIGN:
      Descriptive, bivariate, and hierarchical regression analyses of cross-sectional
      data. SETTING: Howard Brown Health Center, a community-based facility in Chicago,
      Ill, from August 2004 to September 2005. PARTICIPANTS: Three hundred ten YMSM who
      completed an anonymous, computer-assisted survey. MAIN OUTCOME MEASURE:
      Methamphetamine use in the past year. RESULTS: Participants ranged in age from 16
      to 24 years (mean age, 20.3 years); 30% were white and 70% were of other
      race/ethnicity (African American, 33%; Hispanic, 26%; Asian or Pacific Islander,
      3%; and other, 8%). Participants reported many high-risk sexual and substance use
      behaviors. Thirteen percent used methamphetamine in the past year.
      Methamphetamine use was more common among human immunodeficiency virus-infected
      participants (odds ratio, 2.8; 95% confidence interval, 1.3-5.3) and varied by
      age and race/ethnicity; substantially higher prevalence was reported by older and
      non-African American YMSM (P<.001). Compared with other illicit substance users,
      methamphetamine users reported more memory difficulties, impairments in daily
      activities, and unintended risky sex resulting from substance use (all P<.01).
      Hierarchical regression identified sexual risk (unprotected intercourse and
      multiple partners), sexualized social context (eg, Internet sex, sex in a
      bathhouse or sex club, sex with older partners, and commercial sex), lower self
      esteem, and psychological distress as correlated with methamphetamine use among
      participants (P<.05). CONCLUSIONS: A substantial percentage of YMSM in this
      sample used methamphetamine. Methamphetamine use is a public health problem with
      significant implications for the health and well-being of YMSM. Methamphetamine
      use was associated with human immunodeficiency virus-related risk, and patterns
      of use were predicted by demographic data, sexualized social contexts, and
      psychological variables.

PMID- 17548766
TI  - Pediatric patients receiving palliative care in Canada: results of a multicenter
      review.
AB  - OBJECTIVES: To describe the patients who received care from the 8 dedicated
      pediatric palliative care programs in Canada in 2002 and to estimate the number
      of children who may have benefited but did not receive services from these
      programs. DESIGN: Retrospective review of medical records combined with a survey
      of each program. SETTING: Seven pediatric palliative care programs based in
      tertiary care settings and 1 freestanding children's hospice. PARTICIPANTS: The
      programs cared for 317 children during 2002, of whom 123 died during that year.
      An additional 32 children died by the end of 2003. MAIN EXPOSURE: Pediatric
      palliative care program. RESULTS: Nearly half (48.6%) of the patients were
      younger than 5 years, and almost half of these were younger than 1 year. Primary
      diagnoses were disorders of the nervous system (39.1%), malignancies (22.1%), and
      conditions arising in the perinatal period or congenital anomalies (22.1%). Most
      of the children (43.9%) died at home, with those centers reporting more
      comprehensive home care services having the highest percentage of home deaths.
      From a national perspective, between 5% and 12% of the children who could benefit
      from palliative care received services from 1 of these programs. CONCLUSIONS:
      Pediatric palliative care programs in Canada care for a diverse population of
      patients with a wide range of age and disease conditions. Only a small percentage
      of children who die, however, receive services from these dedicated programs.

PMID- 17548767
TI  - Realities of expectorated sputum collection in the pediatric cystic fibrosis
      clinic.
AB  - OBJECTIVES: To determine the proportion of pediatric patients with cystic
      fibrosis who do not produce expectorated sputum during routine ambulatory clinic
      visits and to identify clinical predictors of these patients. DESIGN: Cross
      sectional study. SETTING: The cystic fibrosis clinic at The Hospital for Sick
      Children, Toronto, Ontario. PARTICIPANTS: One hundred eighty-three patients aged
      6 to 18 years who attended the cystic fibrosis clinic between March 1, 2004, and
      November 30, 2004. INTERVENTION: Study patients were asked to expectorate sputum
      for bacterial culture. MAIN OUTCOME MEASURES: The proportion of patients unable
      to produce expectorated sputum was determined. Age, sex, forced expiratory volume
      in 1 second, pancreatic sufficiency, body mass index, and antibiotic use were
      compared between patients producing sputum and those not producing sputum.
      RESULTS: Eighty-three patients (45%) did not expectorate sputum. Patients not
      producing sputum as compared with those producing sputum were younger (mean age,
      10.3 years vs 13.9 years, respectively; difference, 3.6 years; 95% confidence
      interval, 2.6-4.5) and had higher forced expiratory volume in 1 second (mean
      forced expiratory volumes in 1 second, 88% of predicted vs 72% of predicted,
      respectively; difference, 16%; 95% confidence interval, 10.1-22.2). Eighty-eight
      percent of patients not producing sputum had cough and 45% reported sputum
      production at home. CONCLUSIONS: Almost half of pediatric patients with cystic
      fibrosis aged 6 years and older do not expectorate sputum in the clinic, although
      nearly half of these patients do report producing sputum at home. The utility of
      home collection on the morning of a clinic visit and/or hypertonic saline
      induction should be evaluated to increase the number of useful specimens for
      microbiological culture.

PMID- 17548768
TI  - Picture of the month. Congenital sucking blisters.

PMID- 17548769
TI  - Dating violence, sexual assault, and suicide attempts among minority adolescents:
      ending the silence.

PMID- 17548770
TI  - The cost-effectiveness of programs to prevent or reduce obesity: the state of the
      literature and a future research agenda.

PMID- 17548771
TI  - Against newborn screening for type 1 diabetes.

PMID- 17548772
TI  - Only half the story.

PMID- 17548773
TI  - Television viewing, reduced parental utterance, and delayed speech development in
      infants and young children.

PMID- 17548774
TI  - Interpretation of maternal influenza study should not discourage immunization
      efforts.

PMID- 17548775
TI  - Attention and memory in the preclinical stage of dementia.
AB  - The aim of this study was to investigate whether attention may be specifically
      impaired in Alzheimer's disease from the early stages of the disease. Subgroups
      of patients with different types of mild cognitive impairment were selected
      according to standard criteria. Patients and controls were given tasks exploring
      various subcomponents of attention and executive functions. Only subgroups of
      mild cognitive impairment characterized by memory disorders obtained lower scores
      than controls on attention and executive tasks. On the basis of the scores
      obtained on the Clinical Dementia Rating at the 1-year follow-up, patients were
      redistributed into 2 groups: those who developed and those who did not develop
      dementia. Patients who presented evolution to dementia already had, at baseline,
      lower scores than patients who did not evolve on tasks exploring attention and
      executive functions. The results suggest that not only memory disorders but also
      attention/executive deficits may characterize dementia at the onset.

PMID- 17548776
TI  - Conversion to dementia from questionable dementia in an ethnic Chinese
      population.
AB  - We investigated the conversion rate and the risk factors for conversion to
      dementia from questionable dementia in 124 ethnic Chinese subjects with
      questionable dementia at a memory clinic of a university hospital. They were
      evaluated annually based on cognitive testing, the clinical dementia rating
      scale, and a psychiatrist's interview for depression and anxiety. Apolipoprotein
      E genotyping was performed on 111 of these questionable dementia subjects. All
      subjects were evaluated at least twice during the follow-up period of 20.4 +/-
      12.4 months. During that period, 42 questionable dementia subjects were diagnosed
      as having Alzheimer's disease, with an annual conversion rate to dementia of
      19.9%. Compared with the 82 nonconverters, the 42 converters were significantly
      older, had lower cognitive, depression, and anxiety scores, and a higher
      frequency of the apolipoprotein E epsilon4 allele. Cox regression analysis
      revealed that the Alzheimer's disease converters had lower scores for
      orientation, short-term memory, and anxiety, and a higher frequency of the
      apolipoprotein E epsilon4 allele than the nonconverters.

PMID- 17548777
TI  - Cerebral metabolic correlates of the clinical dementia rating scale in mild
      cognitive impairment.
AB  - Mild cognitive impairment (MCI) is often a prodromal state of Alzheimer's disease
      (AD). Imaging studies have shown that metabolic deficits in cerebral regions
      known to be affected early by AD pathology are predictive of progression to AD.
      In the present article, the authors examine associations between clinical
      impairment (Clinical Dementia Rating scale sum of boxes [CDR-SB]) and regional
      deficits in glucose utilization in a sample of 41 patients with MCI, who
      underwent cerebral 18F-FDG PET for the measurement of regional glucose
      metabolism. A linear regression analysis with CDR-SB score as the independent
      variable and glucose metabolism as the dependent variable, adjusted for age,
      gender, and years of school education, was conducted in voxel-by-voxel fashion in
      SPM2. The regression analysis revealed a significant negative association between
      CDR-SB score and glucose metabolism in the right posterior cingulate gyrus (P <
      .001, uncorrected for multiple comparisons), which was independent from
      demographical variables. The authors conclude that clinical severity of
      impairments is already correlated with deficits in glucose metabolism in the
      stage of MCI.

PMID- 17548778
TI  - FMR1 alleles in Parkinson's disease: relation to cognitive decline and
      hallucinations, a longitudinal study.
AB  - Carriers of expanded alleles of the fragile X mental retardation (FMR1) gene may
      display parkinsonism, cognitive decline, and behavioral changes. The authors
      screened 2 male groups of patients affected with Parkinson's disease (PD) (n =
      137). One group (n = 56) was followed longitudinally for up to 12 years. Length
      of CGG repeats in PD patients was compared with healthy controls (n = 310). In
      addition, the association of the number of CGG repeats with cognitive decline or
      hallucinations was studied in the longitudinally followed PD group. The authors
      found no repeats in the premutation range (55-200 CGG repeats) and no significant
      difference in the proportion of intermediate-size (41-54 CGG repeats) carriers
      between the PD and the control groups. Using linear regression, the number of CGG
      repeats was not related to motor or cognitive progression. However, the marked
      cognitive decline in 2 patients carrying intermediate-size alleles points to a
      possible association. More studies with larger PD samples are warranted.

PMID- 17548779
TI  - Polymorphisms and vascular cognitive impairment after ischemic stroke.
AB  - Environmental and genetic factors may both affect the risk of vascular cognitive
      impairment developing after a stroke. To identify factors affecting this risk,
      the cognitive status of 121 patients was examined 3 months after an ischemic
      stroke. In all patients and in 270 control subjects, 7 polymorphisms reported to
      affect risk of vascular ischemic disease were genotyped. In 51 patients (42.1%),
      vascular cognitive impairment resulted, defined by a Mini-Mental State
      Examination score of less than 24. These patients were older and more likely to
      be women. Alleles of none of the polymorphisms differed between patients with or
      without vascular cognitive impairment, except for glutamate-cysteine ligase
      modifier (GCLM) (odds ratio = 2.8, P = .006). When all stroke patients were
      considered, the GCLM genotype did not affect Mini-Mental State Examination
      scores. Testing the GCLM genotype in an independent group of stroke patients may
      determine whether this association with vascular cognitive impairment is genuine.

PMID- 17548780
TI  - Clinical diagnosis of dementia, not behavioral and psychologic symptoms, is
      associated with psychotropic drug use in community-dwelling elders classified as
      having dementia.
AB  - Little is known about the prevalence and correlates of psychotropic drug use in
      community-dwelling elders with dementia. Baseline data from 285 community
      dwelling elders with a research classification of dementia enrolled in the
      observational Memory and Medical Care Study were analyzed. Of these, 33.3% with a
      research classification of dementia were clinically diagnosed, 28.8% used at
      least 1 psychotropic drug, and 61.8% had at least 1 behavioral or psychologic
      symptom of dementia. Presence of a behavioral or psychologic symptom of dementia
      was associated with a higher likelihood of a clinical diagnosis of dementia. A
      clinical diagnosis of dementia, not a behavioral or psychologic symptom of
      dementia, was associated with psychotropics use. Clinical recognition of dementia
      appears to be an intermediate step between presence of symptoms of dementia and
      the prescription of psychotropics. Most community-dwelling elders meeting the
      research criteria for dementia were not clinically diagnosed, despite contact
      with a physician (89%) in the previous year.

PMID- 17548781
TI  - Weight changes during treatment with olanzapine in older adult patients with
      dementia and behavioral disturbances.
AB  - Treatment-emergent weight gain has been reported in younger patients receiving
      atypical antipsychotics, but less is known about weight gain in adults aged 65
      years and older. This was a post hoc analysis of 1267 patients with dementia and
      behavioral disturbances treated with olanzapine (1 to 20 mg/d) in clinical
      trials, most of whom were underweight (body mass index <18.5 kg/m2) or of normal
      weight (body mass index, 18.5-24.9 kg/m2) at baseline. Weight changes over the
      first 20 weeks of treatment in olanzapine-treated patients, as estimated by a
      repeated measures analysis model, were significantly greater in the combined
      categories of underweight and normal weight (1.22 kg and 1.29 kg, respectively)
      versus overweight and obese (0.56 kg and 0.53 kg, respectively; P = .006). The
      estimated probability of gaining more than 7% of initial body weight was
      significantly greater in patients treated with olanzapine versus active
      comparator (P < .001) or placebo (P < .001). Weight gain in olanzapine-treated
      older patients with dementia and behavioral disturbances was significantly
      greater in individuals with a baseline body mass index of less than 25 kg/m2.

PMID- 17548783
TI  - Impact of problem alcohol use on patient behavior and caregiver burden in a
      geriatric assessment clinic.
AB  - There has been a growing interest in understanding issues surrounding alcohol use
      in late life. Information about the relationship of alcohol use to behavioral
      problems in older persons living in the community is particularly limited. This
      study used information obtained from an outpatient geriatric assessment clinic to
      study this relationship and the effects of these behaviors on caregivers. Data on
      alcohol use, problem behaviors, and caregiver burden were collected prospectively
      in consecutive patients undergoing geriatric assessment primarily for cognitive
      problems over a 3-year period. All patients were evaluated by a multidisciplinary
      team, which included a geriatric psychiatrist. The evaluation screened for
      current and/or past alcohol use through interviews with the patient and a
      collateral source. The collateral source also completed the Neuropsychiatric
      Inventory and the Family Burden Scale. Subjects were classified into 2 groups:
      those with a current or past alcohol problem and those with no alcohol problem. A
      total of 349 patients were evaluated, with 17.8% being designated as having a
      current or past alcohol problem. This subgroup represented 35% of the men and 9%
      of the women from the study population. Approximately half of the subgroup was
      actively drinking alcohol. Patients with a history of problem alcohol use,
      regardless of current use and cognitive status, exhibited more behavioral
      disturbances including agitation, irritability, and disinhibition. Their
      caregivers reported significantly higher caregiver distress. Current or past
      alcohol problem use was frequent in this population of frail, older adults
      undergoing geriatric assessment. Regardless of current alcohol use, these
      patients displayed more behavioral disturbances than those without a history of
      problem drinking, and their caregivers experienced significantly more burden. A
      history of problem drinking appears to be a significant marker for behavioral
      disturbances in late life and merits further study.

PMID- 17548782
TI  - Premorbid relationship satisfaction and caregiver burden in dementia caregivers.
AB  - Dementia caregiver appraisal of the quality of their current and premorbid
      relationship with the care recipient is associated with caregiving behaviors,
      caregiver mood, and the decision to end home care. This study examined the
      contribution of premorbid relationship satisfaction to caregiver burden in
      dementia caregivers. Live-in dementia caregivers (n = 72) completed several
      psychosocial measures. Caregiver responses were used to divide them into low
      premorbid relationship satisfaction group (low) versus high premorbid
      relationship satisfaction group (high). Results indicate that premorbid
      relationship satisfaction is negatively associated with caregiver burden and
      quality of family functioning. Caregivers with high satisfaction demonstrated
      significantly less burden and less reactivity to memory and behavior problems,
      and better problem solving skills and more effective communication compared with
      the low caregivers. Findings are independent of length of caregiving, disease
      severity, care recipient daily functioning, and relationship type. Relationship
      satisfaction may be an important contributor to caregiver burden.

PMID- 17548784
TI  - Parental infertility and semen quality in male offspring: a follow-up study.
AB  - Jensen et al. (Am J Epidemiol 2007;165:583-90) reported for the first time that
      men whose mothers had received fertility treatment had poor semen quality. This
      result could be confounded by the mothers' body mass index. Obesity is a strong
      predictor of fecundity and could have a programming effect on semen quality
      through hormonal factors or links to fetal growth. The authors of the current
      study tried to replicate the finding of Jensen et al. after controlling for
      maternal body mass index and other covariates using data from a recently
      conducted, population-based, Danish follow-up study on the association between
      maternal smoking during pregnancy in 1984-1987 and sons' semen quality, in which
      the participants were sampled according to levels of maternal smoking during
      pregnancy. After adjustment, sons of mothers who reported that they had been
      examined or treated for childlessness (n = 30) had a lower sperm concentration
      and total sperm count and fewer motile and morphologically normal spermatozoa in
      comparison with sons of mothers who had not been examined or treated for
      childlessness (n = 295). None of the differences (except for semen concentration)
      between the groups reached statistical significance, but the study has limited
      power. The findings were in the same direction as those reported by Jensen et al.
      and do not indicate that their results are confounded by maternal body mass
      index.

PMID- 17548785
TI  - Association of childhood and adolescent anthropometric factors, physical
      activity, and diet with adult mammographic breast density.
AB  - Early-life exposures may influence the development of breast cancer. The authors
      examined the association of childhood and adolescent anthropometric factors,
      physical activity levels, and diet with adult mammographic breast density, a
      strong risk factor for breast cancer. Women in the Minnesota Breast Cancer Family
      Study cohort who had undergone mammograms but had not had breast cancer (n=1,893)
      formed the sample. Information on adolescent exposures, including relative
      height, weight, and physical activity at ages 7, 12, and 18 years and diet at age
      12-13 years, was self-reported during two follow-up studies (1990-2003).
      Mammographic percent density was estimated using a computer-assisted thresholding
      program. Statistical analyses were performed using linear mixed-effects models
      with two-sided tests. Positive associations with height at ages 7 (p<0.001), 12
      (p<0.001), and 18 (p<0.001) years and percent density were evident overall and
      within menopausal status categories. The minimum difference in percent density
      between the tallest and shortest girls was 3 percent, with a maximum of 7
      percent. Weight at age 12 years (p=0.005) and adiposity at age 12 years (p=0.005)
      were both inversely associated with adult percent density. Adolescent physical
      activity and diet were unrelated to percent density. These results suggest that
      adolescent height, a known risk factor for breast cancer, is also associated with
      mammographic percent density.

PMID- 17548786
TI  - Cigarette smoking and cancer risk: modeling total exposure and intensity.
AB  - A recent analysis showed that the excess odds ratio (EOR) for lung cancer due to
      smoking can be modeled by a function which is linear in total pack-years and
      exponential in the logarithm of smoking intensity and its square. Below 15-20
      cigarettes per day, the EOR/pack-year increased with intensity (direct exposure
      rate or enhanced potency effect), suggesting greater risk for a total exposure
      delivered at higher intensity (for a shorter duration) than for an equivalent
      exposure delivered at lower intensity. Above 20 cigarettes per day, the EOR/pack
      year decreased with increasing intensity (inverse exposure rate or reduced
      potency effect), suggesting greater risk for a total exposure delivered at lower
      intensity (for a longer duration) than for an equivalent exposure delivered at
      higher intensity. The authors applied this model to data from 10 case-control
      studies of cancer, including cancers of the lung, bladder, oral cavity, pancreas,
      and esophagus. At lower intensities, there was enhanced potency for several
      cancer sites, but narrow ranges for pack-years increased uncertainty, precluding
      definitive conclusions. At higher intensities, there was a consistent reduced
      potency effect across studies. The intensity effects were statistically
      homogeneous, indicating that after accounting for risk from total pack-years,
      intensity patterns were comparable across the diverse cancer sites.

PMID- 17548787
TI  - Influence of maternal smoking on placental abruption in successive pregnancies: a
      population-based prospective cohort study in Sweden.
AB  - The authors examined associations between cumulative smoking during a woman's
      first and second pregnancies and risk of placental abruption in the second
      pregnancy. They performed a population-based prospective cohort study of 526,690
      women who delivered their first two consecutive singletons in Sweden in 1983
      2001. Using logistic regression models, the authors found that, among women
      without placental abruption in the first pregnancy, smoking was associated with
      increased risk of abruption in the second pregnancy; however, this effect was
      confined to exposure occurring during the second pregnancy (adjusted odds ratio
      (OR)=1.8, 95% confidence interval (CI): 1.4, 2.3) but not the first (adjusted
      OR=1.1, 95% CI: 0.9, 1.3). Among women with a prior abruption, the risk of
      repeating abruption was increased irrespective of smoking habits. When women
      smoked during both pregnancies, there was an almost 11-fold increase in risk
      (adjusted OR=10.9, 95% CI: 7.3, 16.3). These findings suggest that women who quit
      smoking before pregnancy may benefit from reduced risk of abruption. The
      observation that the recurrence of abruption is substantially increased
      regardless of changes in smoking habits suggests that factors other than smoking
      may influence the recurrence of placental abruption.

PMID- 17548789
TI  - Advances in the use of milk thistle (Silybum marianum).
AB  - Milk thistle (Silybum marianum) is an herbal supplement used to treat liver and
      biliary disorders. Silymarin, a mixture of flavanoid complexes, is the active
      component that protects liver and kidney cells from toxic effects of drugs,
      including chemotherapy. Although milk thistle has not significantly altered the
      course of chronic liver disease, it has reduced liver enzyme levels and
      demonstrated anti-inflammatory and T cell-modulating effects. There is strong
      preclinical evidence for silymarin's hepatoprotective and anticarcinogenic
      effects, including inhibition of cancer cell growth in human prostate, skin,
      breast, and cervical cells. Milk thistle is considered safe and well-tolerated,
      with gastrointestinal upset, a mild laxative effect, and rare allergic reaction
      being the only adverse events reported when taken within the recommended dose
      range. More clinical trials of rigorous methodology, using standardized and well
      defined products and dosages, are needed to evaluate the potential of silymarin
      against liver toxicity, chronic liver disease, and human cancers.

PMID- 17548790
TI  - Milk thistle nomenclature: why it matters in cancer research and pharmacokinetic
      studies.
AB  - Extracts of milk thistle have been recognized for centuries as "liver tonics" and
      are well-known to prevent or reverse hepatotoxicity of reactive drug metabolites
      or naturally occurring toxins. Milk thistle extracts are now under intense study
      in the experimental therapeutics of cancer for chemoprevention, treatment, and
      amelioration of chemotherapy side effects. Precision in nomenclature, however,
      has lagged behind this progress. The crude commercial product of milk thistle is
      termed silymarin, a complex of at least 7 flavonolignans and 1 flavonoid that
      comprises 65% to 80% of milk thistle extract. From silymarin is derived
      silibinin, a semipurified fraction once thought to be a single compound but now
      recognized as a 1:1 mixture of 2 diastereoisomers, silybin A and silybin B. The
      distinction between silymarin and silibinin is not only important to
      understanding the historical literature, but thorough characterization and use of
      chemically defined mixtures in preclinical and clinical studies are essential to
      the progress of these botanical compounds as human therapeutics. As a result, we
      urge clinicians and preclinical investigators alike to exercise rigor in
      nomenclature and use pure compounds or precisely defined chemical mixtures in
      subsequent studies. Herein, we provide a guide to the proper nomenclature and
      composition of milk thistle extracts and discuss the known pharmacokinetic
      studies of these botanical medicines. The drug-interaction potential of these
      extracts appears to be quite low, and in fact, silibinin appears to synergize
      with the antitumor effects of some commonly used chemotherapeutics. However, some
      precautions are advised as high-dose, phase II studies are conducted.

PMID- 17548791
TI  - Toward the definition of the mechanism of action of silymarin: activities related
      to cellular protection from toxic damage induced by chemotherapy.
AB  - Silymarin, the active extract from milk thistle, has been extensively used in
      patients with liver disease of different etiology. Although silymarin is a
      complex of 7 flavonolignans and polyphenols, silibinin is usually regarded as the
      most active component. In vitro and in vivo studies indicate that silymarin and
      silibinin protect the liver from oxidative stress and sustained inflammatory
      processes, mainly driven by Reactive Oxygen Species (ROS) and secondary
      cytokines. Oxidative stress and inflammation are also involved in cellular damage
      of many other tissues and their role in the development and toxic reactions in
      patients receiving cancer therapies is established. The protective effects of
      silymarin and silibinin, demonstrated in various tissues, suggest a clinical
      application in cancer patients as an adjunct to established therapies, to prevent
      or reduce their toxicity. Here we discuss the possible mechanism of the
      protective action of silymarin and silibinin, focusing on cancer therapies as
      agents causing cellular damage.

PMID- 17548792
TI  - Chemopreventive efficacy of silymarin in skin and prostate cancer.
AB  - Prevention and therapeutic intervention by phytochemicals are newer dimensions in
      the arena of cancer management. In this regard, the cancer chemopreventive role
      of silymarin (Silybum marianum) has been extensively studied and has shown
      anticancer efficacy against various cancer sites, especially skin and prostate.
      In skin cancer, silymarin treatment inhibits ultraviolet B radiation or
      chemically initiated or promoted carcinogenesis. These effects of silymarin
      against skin carcinogenesis have been attributed to its strong antioxidant and
      anti-inflammatory action as well as its inhibitory effect on mitogenic signaling.
      Similarly, silymarin treatment inhibits 3, 2-dimethyl-4-aminobiphenyl-induced
      prostate carcinogenesis and retards the growth of advanced prostate tumor
      xenograft in athymic nude mice. In prostate cancer, silymarin treatment down
      regulates androgen receptor-, epidermal growth factor receptor-, and nuclear
      factor-kappaB- mediated signaling and induces cell cycle arrest. Extensive
      preclinical findings have supported the anticancer potential of silymarin, and
      now its efficacy is being evaluated in cancer patients.

PMID- 17548793
TI  - Review of clinical trials evaluating safety and efficacy of milk thistle (Silybum
      marianum [L.] Gaertn.).
AB  - Milk thistle extracts have been used as traditional herbal remedies for almost
      2000 years. The extracts are still widely used to protect the liver against
      toxins and to control chronic liver diseases. Recent experimental and clinical
      studies suggest that milk thistle extracts also have anticancer, antidiabetic,
      and cardioprotective effects. This article reviews clinical trials of milk
      thistle conducted in the past 5 years including pharmacokinetic and toxicity
      studies, herb-drug interactions, and other safety issues. Several trials have
      studied the effects of milk thistle for patients with liver diseases, cancer,
      hepatitis C, HIV, diabetes, and hypercholesterolemia. Promising results have been
      reported in the protective effect of milk thistle in certain types of cancer, and
      ongoing trials will provide more evidence about this effect. In addition, new
      established doses and improvement on the quality and standardization of this herb
      will provide the much-awaited evidence about the efficacy of milk thistle in the
      treatment of liver diseases. Milk thistle extracts are known to be safe and well
      tolerated, and toxic or adverse effects observed in the reviewed clinical trials
      seem to be minimal. The future of milk thistle research is promising, and high
      quality randomized clinical trials on milk thistle versus placebo may be needed
      to further demonstrate the safety and efficacy of this herb.

PMID- 17548794
TI  - Clinical applications of Silybum marianum in oncology.
AB  - Milk thistle (Silybum marianum) is an herb that is increasingly used in oncology
      research and treatment settings. Historically, it has been used to treat liver
      and biliary disorders and has been used in detoxification and cleansing
      protocols. However, milk thistle is increasingly being investigated for its use
      in adult and pediatric populations for oncology indications. Possible indications
      during cancer treatment include cleansing and detoxification after chemotherapy,
      preventing hepatotoxicity during chemotherapy, treating hepatotoxicity after
      chemotherapy, and potentiating chemotherapy and radiation therapy as an
      adjunctive treatment. Milk thistle may also have applications in ameliorating
      long-term hepatic and cardiovascular effects of cancer treatment. Preliminary
      studies are investigating its use as a chemopreventive agent and possibly to
      treat cancer directly. Much of milk thistle's current clinical use grows out of
      historical uses but is informed by an increasing number of clinical trials and
      animal studies. This article provides an overview of the current clinical
      applications of milk thistle in the oncology setting, including guidelines on
      commonly used forms and doses.

PMID- 17548795
TI  - Future directions for research on Silybum marianum for cancer patients.
AB  - Silymarin (Silybum marianum [L.] Gaertn. [Asteraceae]) is a promising agent for
      cancer prevention, adjuvant cancer treatment, and reduction of iatrogenic
      toxicity. Although it is safe and free of serious adverse side effects, few
      studies have evaluated its use alongside conventional cytotoxic therapies, and
      adverse events associated with long-term administration are uncertain. Although
      it may prevent some types of cancer, its promotion of tissue regeneration and its
      potential estrogen activity could promote the growth of some tumors. Further
      clinical trials using authenticated fractions of silymarin as simple and complex
      derivatives are required prior to any general recommendations. Future research
      should focus on authentication of active chemicals, pharmacokinetics, adverse
      interactions and quality control, prevention of cancer initiation and
      progression, adjuvant therapy for specific cancers, and prevention of toxicity
      from anticancer therapies.

PMID- 17548796
TI  - Patients' experiences and perceptions of a consultative model integrative
      medicine clinic: a qualitative study.
AB  - OBJECTIVE: A common theme in integrative medicine (IM) is patient-centered
      partnering in care between patients and providers. Despite the stated ideals, few
      studies have assessed patients' perspectives on their actual experience in the
      context of a specific care model. The purpose of the present study was to
      retrospectively explore and compare experiences of cancer and noncancer patients
      under care in a consultative IM outpatient teaching clinic in the south-western
      United States. DESIGN: Qualitative study using inductive content analysis of
      focus group interview transcripts (2 groups of adult patients with cancers of
      various types and 1 group of chronically ill noncancer patients with mixed
      diagnoses). METHOD: Participants were recruited by random selection from a pool
      of eligible patients. Groups were conducted with patients who had completed their
      initial conventional cancer treatment and were at least 6 months postconsultation
      with an IM clinic physician. Transcripts of the audiotaped focus groups were
      analyzed. RESULTS: Cancer patients (n = 15) and noncancer patients (n = 6) (mean
      age, 60 years; 77% women) expressed overall satisfaction with IM, emphasizing (1)
      expansion of treatment options with lower perceived toxicity than conventional
      therapies, (2) positive experiences of the IM physician as caring and taking time
      to listen, and (3) improved self-care skills and sense of empowerment. Cancer
      patients noted positive relationships with their conventional MDs more than did
      noncancer patients, although both groups appreciated the IM physicians'
      communication styles. CONCLUSION: Patients experience a consultative integrative
      clinic model overall as favorable. The impact on outcomes, costs, and long-term
      quality of life requires additional study.

PMID- 17548797
TI  - Effect of amentoflavone on the inhibition of pulmonary metastasis induced by B16F
      10 melanoma cells in C57BL/6 mice.
AB  - This study was an investigation of the antimetastatic activity of amentoflavone
      using B16F-10 melanoma-induced experimental lung metastasis in C57BL/6 mice.
      Amentoflavone treatment significantly reduced tumor nodule formation accompanied
      by reduced lung collagen hydroxyproline, hexosamine, and uronic acid levels.
      Serum sialic acid and gammaglutamyl transpeptidase levels were also significantly
      inhibited after amentoflavone treatment. Amentoflavone treatment up-regulated the
      lung tissue inhibitor of metalloprotease-1 and tissue inhibitor of
      metalloprotease-2 expression. The cytokine profile and growth factors such as
      interleukin-1beta , interleukin-6, tumor necrosis factor-alpha, granulocyte
      monocyte- colony stimulating factor, vascular endothelial growth factor,
      interleukin-2, and tissue inhibitor of metalloprotease-1 in the serum of these
      animals were markedly altered after amentoflavone treatment. This altered level
      of cytokines after amentoflavone treatment was also accompanied by enhanced
      natural killer cell antibody-dependent cellular cytotoxicity. The study reveals
      that amentoflavone treatment could alter proinflammatory cytokine production and
      could inhibit the activation and nuclear translocation of p65, p50, c-Rel
      subunits of nuclear factor-kappaB, and other transcription factors such as c-fos,
      activated transcription factor-2, and cyclic adenosine monophosphate response
      element-binding protein in B16F-10 melanoma cells.

PMID- 17548798
TI  - Cortical connections of area V4 in the macaque.
AB  - To determine the locus, full extent, and topographic organization of cortical
      connections of area V4 (visual area 4), we injected anterograde and retrograde
      tracers under electrophysiological guidance into 21 sites in 9 macaques.
      Injection sites included representations ranging from central to far peripheral
      eccentricities in the upper and lower fields. Our results indicated that all
      parts of V4 are connected with occipital areas V2 (visual area 2), V3 (visual
      area 3), and V3A (visual complex V3, part A), superior temporal areas V4t (V4
      transition zone), MT (medial temporal area), and FST (fundus of the superior
      temporal sulcus [STS] area), inferior temporal areas TEO (cytoarchitectonic area
      TEO in posterior inferior temporal cortex) and TE (cytoarchitectonic area TE in
      anterior temporal cortex), and the frontal eye field (FEF). By contrast, mainly
      peripheral field representations of V4 are connected with occipitoparietal areas
      DP (dorsal prelunate area), VIP (ventral intraparietal area), LIP (lateral
      intraparietal area), PIP (posterior intraparietal area), parieto-occipital area,
      and MST (medial STS area), and parahippocampal area TF (cytoarchitectonic area TF
      on the parahippocampal gyrus). Based on the distribution of labeled cells and
      terminals, projections from V4 to V2 and V3 are feedback, those to V3A, V4t, MT,
      DP, VIP, PIP, and FEF are the intermediate type, and those to FST, MST, LIP, TEO,
      TE, and TF are feedforward. Peripheral field projections from V4 to parietal
      areas could provide a direct route for rapid activation of circuits serving
      spatial vision and spatial attention. By contrast, the predominance of central
      field projections from V4 to inferior temporal areas is consistent with the need
      for detailed form analysis for object vision.

PMID- 17548799
TI  - The spatiotemporal dynamics of autobiographical memory: neural correlates of
      recall, emotional intensity, and reliving.
AB  - We sought to map the time course of autobiographical memory retrieval, including
      brain regions that mediate phenomenological experiences of reliving and emotional
      intensity. Participants recalled personal memories to auditory word cues during
      event-related functional magnetic resonance imaging (fMRI). Participants pressed
      a button when a memory was accessed, maintained and elaborated the memory, and
      then gave subjective ratings of emotion and reliving. A novel fMRI approach based
      on timing differences capitalized on the protracted reconstructive process of
      autobiographical memory to segregate brain areas contributing to initial access
      and later elaboration and maintenance of episodic memories. The initial period
      engaged hippocampal, retrosplenial, and medial and right prefrontal activity,
      whereas the later period recruited visual, precuneus, and left prefrontal
      activity. Emotional intensity ratings were correlated with activity in several
      regions, including the amygdala and the hippocampus during the initial period.
      Reliving ratings were correlated with activity in visual cortex and ventromedial
      and inferior prefrontal regions during the later period. Frontopolar cortex was
      the only brain region sensitive to emotional intensity across both periods.
      Results were confirmed by time-locked averages of the fMRI signal. The findings
      indicate dynamic recruitment of emotion-, memory-, and sensory-related brain
      regions during remembering and their dissociable contributions to
      phenomenological features of the memories.

PMID- 17548800
TI  - Monosynaptic connections between pairs of L5A pyramidal neurons in columns of
      juvenile rat somatosensory cortex.
AB  - Layer 5 (L5) of somatosensory cortex is a major gateway for projections to intra-
      and subcortical brain regions. This layer is further divided into 5A and 5B
      characterized by relatively separate afferent and efferent connections. Little is
      known about the organization of connections within L5A of neocortical columns. We
      therefore used paired recordings to probe the anatomy and physiology of
      monosynaptic connections between L5A pyramidal neurons within the barrel columns
      of somatosensory cortex in acute slices of approximately 3-week-old rats. Post
      hoc reconstruction and calculation of the axodendritic overlap of pre- and
      postsynaptic neurons, together with identification of putative synaptic contacts
      (3.5 per connection), indicated a preferred innervation domain in the proximal
      dendritic region. Synaptic transmission was reliable (failure rate <2%) and had a
      low variability (coefficient of variation of 0.3). Unitary excitatory
      postsynaptic potential (EPSP) amplitudes varied 30-fold with a mean of 1.2 mV and
      displayed depression over a wide range of frequencies (2-100 Hz) during bursts of
      presynaptic firing. A single L5A pyramidal neuron was estimated to target
      approximately 270 other pyramidal neurons within the same layer of its home
      barrel column, suggesting a mechanism of feed-forward excitation by which
      synchronized single action potentials are efficiently transmitted within L5A of
      juvenile cortex.

PMID- 17548801
TI  - Kinesthetic working memory and action control within the dorsal stream.
AB  - There is wide agreement that the "dorsal (action) stream" processes visual
      information for movement control. However, movements depend not only on vision
      but also on tactile and kinesthetic information (=haptics). Using functional
      magnetic resonance imaging, the present study investigates to what extent
      networks within the dorsal stream are also utilized for kinesthetic action
      control and whether they are also involved in kinesthetic working memory.
      Fourteen blindfolded participants performed a delayed-recognition task in which
      right-handed movements had to be encoded, maintained, and later recognized
      without any visual feedback. Encoding of hand movements activated somatosensory
      areas, superior parietal lobe (dorsodorsal stream), anterior intraparietal sulcus
      (aIPS) and adjoining areas (ventrodorsal stream), premotor cortex, and
      occipitotemporal cortex (ventral stream). Short-term maintenance of kinesthetic
      information elicited load-dependent activity in the aIPS and adjacent anterior
      portion of the superior parietal lobe (ventrodorsal stream) of the left
      hemisphere. We propose that the action representation system of the dorsodorsal
      and ventrodorsal stream is utilized not only for visual but also for kinesthetic
      action control. Moreover, the present findings demonstrate that networks within
      the ventrodorsal stream, in particular the left aIPS and closely adjacent areas,
      are also engaged in working memory maintenance of kinesthetic information.

PMID- 17548802
TI  - Dynamic signals related to choices and outcomes in the dorsolateral prefrontal
      cortex.
AB  - Although economic theories based on utility maximization account for a range of
      choice behaviors, utilities must be estimated through experience. Dynamics of
      this learning process may account for certain discrepancies between the
      predictions of economic theories and real choice behaviors of humans and other
      animals. To understand the neural mechanisms responsible for such adaptive
      decision making, we trained rhesus monkeys to play a simulated matching pennies
      game. Small but systematic deviations of the animal's behavior from the optimal
      strategy were consistent with the predictions of reinforcement learning theory.
      In addition, individual neurons in the dorsolateral prefrontal cortex (DLPFC)
      encoded 3 different types of signals that can potentially influence the animal's
      future choices. First, activity modulated by the animal's previous choices might
      provide the eligibility trace that can be used to attribute a particular outcome
      to its causative action. Second, activity related to the animal's rewards in the
      previous trials might be used to compute an average reward rate. Finally,
      activity of some neurons was modulated by the computer's choices in the previous
      trials and may reflect the process of updating the value functions. These results
      suggest that the DLPFC might be an important node in the cortical network of
      decision making.

PMID- 17548803
TI  - Visual spatial representation in mathematical problem solving by deaf and hearing
      students.
AB  - This research examined the use of visual-spatial representation by deaf and
      hearing students while solving mathematical problems. The connection between
      spatial skills and success in mathematics performance has long been established
      in the literature. This study examined the distinction between visual-spatial
      "schematic" representations that encode the spatial relations described in a
      problem versus visual-spatial "pictorial" representations that encode only the
      visual appearance of the objects described in a problem. A total of 305 hearing
      (n = 156) and deaf (n = 149) participants from middle school, high school, and
      college participated in this study. At all educational levels, the hearing
      students performed significantly better in solving the mathematical problems
      compared to their deaf peers. Although the deaf baccalaureate students exhibited
      the highest performance of all the deaf participants, they only performed as well
      as the hearing middle school students who were the lowest scoring hearing group.
      Deaf students remained flat in their performance on the mathematical problem
      solving task from middle school through the college associate degree level. The
      analysis of the students' problem representations showed that the hearing
      participants utilized visual-spatial schematic representation to a greater extent
      than did the deaf participants. However, the use of visual-spatial schematic
      representations was a stronger positive predictor of mathematical problem-solving
      performance for the deaf students. When deaf students' problem representation
      focused simply on the visual-spatial pictorial or iconic aspects of the
      mathematical problems, there was a negative predictive relationship with their
      problem-solving performance. On two measures of visual-spatial abilities, the
      hearing students in high school and college performed significantly better than
      their deaf peers.

PMID- 17548804
TI  - Factors predicting recall of mathematics terms by deaf students: implications for
      teaching.
AB  - In this study of deaf high school students, imagery and familiarity were found to
      be the best predictors of geometry word recall, whereas neither concreteness nor
      signability of the terms was a significant predictor variable. Recall of high
      imagery terms was significantly better than for low imagery terms, and the same
      result was found for high- over low-familiarity and signability. Concrete terms
      were recalled significantly better than abstract terms. Geometry terms that could
      be represented with single signs were recalled significantly better than those
      that are usually fingerspelled or those represented by compound signs. Teachers
      with degrees and/or certification in mathematics had significantly higher self
      ratings for the strongest predictor variables, imagery (visualization), and
      familiarity, as compared with those without such formal training. Based on these
      findings, implications for mathematics instruction, teacher education, and
      research are provided.

PMID- 17548805
TI  - Contribution of implicit sequence learning to spoken language processing: some
      preliminary findings with hearing adults.
AB  - Spoken language consists of a complex, sequentially arrayed signal that contains
      patterns that can be described in terms of statistical relations among language
      units. Previous research has suggested that a domain-general ability to learn
      structured sequential patterns may underlie language acquisition. To test this
      prediction, we examined the extent to which implicit sequence learning of
      probabilistically structured patterns in hearing adults is correlated with a
      spoken sentence perception task under degraded listening conditions. Performance
      on the sentence perception task was found to be correlated with implicit sequence
      learning, but only when the sequences were composed of stimuli that were easy to
      encode verbally. Implicit learning of phonological sequences thus appears to
      underlie spoken language processing and may indicate a hitherto unexplored
      cognitive factor that may account for the enormous variability in language
      outcomes in deaf children with cochlear implants. The present findings highlight
      the importance of investigating individual differences in specific cognitive
      abilities as a way to understand and explain language in deaf learners and, in
      particular, variability in language outcomes following cochlear implantation.

PMID- 17548806
TI  - Pivotal Advance: Inhibition of MyD88 dimerization and recruitment of IRAK1 and
      IRAK4 by a novel peptidomimetic compound.
AB  - MyD88 is an adaptor protein, which plays an essential role in the intracellular
      signaling elicited by IL-1R and several TLRs. Central to its function is the
      ability of its Toll/IL-1R translation initiation region (TIR) domain to
      heterodimerize with the receptor and to homodimerize with another MyD88 molecule
      to favor the recruitment of downstream signaling molecules such as the
      serine/threonine kinases IL-1R-associated kinase 1 (IRAK1) and IRAK4. Herein, we
      have synthesized and tested the activity of a synthetic peptido-mimetic compound
      (ST2825) modeled after the structure of a heptapeptide in the BB-loop of the
      MyD88-TIR domain, which interferes with MyD88 signaling. ST2825 inhibited MyD88
      dimerization in coimmunoprecipitation experiments. This effect was specific for
      homodimerization of the TIR domains and did not affect homodimerization of the
      death domains. Moreover, ST2825 interfered with recruitment of IRAK1 and IRAK4 by
      MyD88, causing inhibition of IL-1beta-mediated activation of NF-kappaB
      transcriptional activity. After oral administration, ST2825 dose-dependently
      inhibited IL-1beta-induced production of IL-6 in treated mice. Finally, we
      observed that ST2825 suppressed B cell proliferation and differentiation into
      plasma cells in response to CpG-induced activation of TLR9, a receptor that
      requires MyD88 for intracellular signaling. Our results indicate that ST2825
      blocks IL-1R/TLR signaling by interfering with MyD88 homodimerization and suggest
      that it may have therapeutic potential in treatment of chronic inflammatory
      diseases.

PMID- 17548807
TI  - TORC2 regulates germinal center repression of the TCL1 oncoprotein to promote B
      cell development and inhibit transformation.
AB  - Aberrant expression of the TCL1 oncoprotein promotes malignant transformation of
      germinal center (GC) B cells. Repression of TCL1 in GC B cells facilitates FAS
      mediated apoptosis and prevents lymphoma formation. However, the mechanism for
      this repression is unknown. Here we show that the CREB coactivator TORC2 directly
      regulates TCL1 expression independent of CREB Ser-133 phosphorylation and
      CBP/p300 recruitment. GC signaling through CD40 or the BCR, which activates pCREB
      dependent genes, caused TORC2 phosphorylation, cytosolic emigration, and TCL1
      repression. Signaling via cAMP-inducible pathways inhibited TCL1 repression and
      reduced apoptosis, consistent with a prosurvival role for TCL1 before GC
      selection and supporting an initiating role for aberrant TCL1 expression during
      GC lymphomagenesis. Our data indicate that a novel CREB/TORC2 regulatory mode
      controls the normal program of GC gene activation and repression that promotes B
      cell development and circumvents oncogenic progression. Our results also
      reconcile a paradox in which signals that activate pCREB/CBP/p300 genes
      concurrently repress TCL1 to initiate its silencing.

PMID- 17548808
TI  - 82,000-year-old shell beads from North Africa and implications for the origins of
      modern human behavior.
AB  - The first appearance of explicitly symbolic objects in the archaeological record
      marks a fundamental stage in the emergence of modern social behavior in Homo.
      Ornaments such as shell beads represent some of the earliest objects of this
      kind. We report on examples of perforated Nassarius gibbosulus shell beads from
      Grotte des Pigeons (Taforalt, Morocco), North Africa. These marine shells come
      from archaeological levels dated by luminescence and uranium-series techniques to
      approximately 82,000 years ago. They confirm evidence of similar ornaments from
      other less well dated sites in North Africa and adjacent areas of southwest Asia.
      The shells are of the same genus as shell beads from slightly younger levels at
      Blombos Cave in South Africa. Wear patterns on the shells imply that some of them
      were suspended, and, as at Blombos, they were covered in red ochre. These
      findings imply an early distribution of bead-making in Africa and southwest Asia
      at least 40 millennia before the appearance of similar cultural manifestations in
      Europe.

PMID- 17548809
TI  - Monotherapy with a tumor-targeting mutant of Salmonella typhimurium cures
      orthotopic metastatic mouse models of human prostate cancer.
AB  - Bacterial infection occasionally has a marked therapeutic effect on malignancies,
      as noted as early as the 19th century. Recently, there have been attempts to
      develop cancer treatment by using tumor-targeting bacteria. These treatments were
      developed to deliver therapeutic molecules specifically to tumors. Researchers
      used anaerobic microorganisms that preferentially grew in necrotic tumor areas.
      However, the resulting tumor killing was, at best, limited. We have developed a
      far more effective bacterial cancer therapy by targeting viable tumor tissue by
      using Salmonella typhimurium leu-arg auxotrophs. Although these bacteria grow in
      viable as well as necrotic areas of tumors, the nutritional auxo trophy severely
      restricts growth in normal tissue. In the current study, we measured the
      antitumor efficacy of the S. typhimurium A1-R mutant, which is auxotrophic for
      leu-arg and has increased antitumor virulence selected by tumor passage. A1-R was
      used to treat metastatic PC-3 human prostate tumors that had been orthotopically
      implanted in nude mice. GFP was used to image tumor and metastatic growth. Of the
      10 mice with the PC-3 tumors that were injected weekly with S. typhimurium A1-R,
      7 were alive and well at the time the last untreated mouse died. Four A1-R
      treated mice remain alive and well 6 months after implantation. Ten additional
      nontumor-bearing mice were injected weekly to determine the toxicity of S.
      typhimurium A1-R. No toxic effects were observed. The approach described here,
      where bacterial monotherapy effectively treats metastatic prostate tumors, is a
      significant improvement over previous bacterial tumor-therapy strategies that
      require combination with toxic chemotherapy.

PMID- 17548811
TI  - Madden-Julian Oscillation analog and intraseasonal variability in a multicloud
      model above the equator.
AB  - The Madden-Julian Oscillation (MJO) is the dominant component of tropical
      intraseasonal variability, and a theory explaining its structure and successful
      numerical simulation remains a major challenge. A successful model for the MJO
      should have a propagation speed of 4-7 m/s predicted by theory; a wavenumber-2 or
      -3 structure for the planetary-scale, low-frequency envelope with distinct active
      and inactive phases of deep convection; an intermittent turbulent chaotic
      multiscale structure within the planetary envelope involving embedded westward-
      and eastward-propagating deep convection events; and qualitative features of the
      low-frequency envelope from the observational record regarding, e.g., its zonal
      flow structure and heating. Here, such an MJO analog is produced by using the
      recent multicloud model of Khouider and Majda in an appropriate intraseasonal
      parameter regime for flows above the equator so that rotation is ignored. Key
      features of the multicloud model are (i) systematic low-level moisture
      convergence with retained conservation of vertically integrated moist static
      energy, and (ii) the use of three cumulus cloud types (congestus, stratiform, and
      deep convective) together with their differing vertical heating structures.
      Besides all of the above structure in the MJO analog waves, there are accurate
      predictions of the phase speed from linear theory and transitions from weak,
      regular MJO analog waves to strong, multiscale MJO analog waves as climatological
      parameters vary. With all of this structure in a simplified context, these models
      should be useful for MJO predictability studies in a fashion akin to the Lorenz
      96 model for the midlatitude atmosphere.

PMID- 17548810
TI  - Herpes simplex virus glycoproteins gB and gH function in fusion between the
      virion envelope and the outer nuclear membrane.
AB  - Herpesviruses must traverse the nuclear envelope to gain access to the cytoplasm
      and, ultimately, to exit cells. It is believed that herpesvirus nucleocapsids
      enter the perinuclear space by budding through the inner nuclear membrane (NM).
      To reach the cytoplasm these enveloped particles must fuse with the outer NM and
      the unenveloped capsids then acquire a second envelope in the trans-Golgi
      network. Little is known about the process by which herpesviruses virions fuse
      with the outer NM. Here we show that a herpes simplex virus (HSV) mutant lacking
      both the two putative fusion glycoproteins gB and gH failed to cross the nuclear
      envelope. Enveloped virions accumulated in the perinuclear space or in membrane
      vesicles that bulged into the nucleoplasm (herniations). By contrast, mutants
      lacking just gB or gH showed only minor or no defects in nuclear egress. We
      concluded that either HSV gB or gH can promote fusion between the virion envelope
      and the outer NM. It is noteworthy that fusion associated with HSV entry requires
      the cooperative action of both gB and gH, suggesting that the two types of fusion
      (egress versus entry) are dissimilar processes.

PMID- 17548812
TI  - Stochastic innovation as a mechanism by which catalysts might self-assemble into
      chemical reaction networks.
AB  - We develop a computer model for how two different chemical catalysts in solution,
      A and B, could be driven to form AB complexes, based on the concentration
      gradients of a substrate or product that they share in common. If A's product is
      B's substrate, B will be attracted to A, mediated by a common resource that is
      not otherwise plentiful in the environment. By this simple physicochemical
      mechanism, chemical reactions could spontaneously associate to become chained
      together in solution. According to the model, such catalyst self-association
      processes may resemble other processes of "stochastic innovation," such as
      Darwinian evolution in biology, that involve a search among options, a selection
      among those options, and then a lock-in of that selection. Like Darwinian
      processes, this simple chemical process exhibits cooperation, competition,
      innovation, and a preference for consistency. This model may be useful for
      understanding organizational processes in prebiotic chemistry and for developing
      new kinds of self-organization in chemically reacting systems.

PMID- 17548813
TI  - Global distribution of negative cofactor 2 subunit-alpha on human promoters.
AB  - Negative cofactor 2 (NC2) forms a stable complex with TATA-binding protein (TBP)
      on promoters in vitro. Its association with TBP prevents the binding of TFIIB and
      leads to inhibition of preinitiation complex formation. Here, we investigate the
      association of NC2 subunit-alpha with human RNA polymerase II promoter regions by
      using gene-specific ChIP and genome-wide promoter ChIPchip analyses. We find
      NC2alpha associated with a large number of human promoters, where it peaks close
      to the core regions. NC2 occupancy in vivo positively correlates with mRNA
      levels, which perhaps reflects its capacity to stabilize TBP on promoter regions.
      In single gene analyses, we confirm core promoter binding and in addition map the
      NC2 complex to enhancer proximal regions. High-occupancy histone genes display a
      stable NC2/TFIIB ratio during the cell cycle, which otherwise varies markedly
      from one gene to another. The latter is at least in part explained by an observed
      negative correlation of NC2 occupancy with the presence of the TFIIB recognition
      element in core promoter regions. Our data establish the genome-wide basis for
      general and gene-specific functions of NC2 in mammalian cells.

PMID- 17548814
TI  - Phenotypic characterization of human colorectal cancer stem cells.
AB  - Recent observations indicate that, in several types of human cancer, only a
      phenotypic subset of cancer cells within each tumor is capable of initiating
      tumor growth. This functional subset of cancer cells is operationally defined as
      the "cancer stem cell" (CSC) subset. Here we developed a CSC model for the study
      of human colorectal cancer (CRC). Solid CRC tissues, either primary tissues
      collected from surgical specimens or xenografts established in nonobese
      diabetic/severe combined immunodeficient (NOD/SCID) mice, were disaggregated into
      single-cell suspensions and analyzed by flow cytometry. Surface markers that
      displayed intratumor heterogeneous expression among epithelial cancer cells were
      selected for cell sorting and tumorigenicity experiments. Individual phenotypic
      cancer cell subsets were purified, and their tumor-initiating properties were
      investigated by injection in NOD/SCID mice. Our observations indicate that, in
      six of six human CRC tested, the ability to engraft in vivo in immunodeficient
      mice was restricted to a minority subpopulation of epithelial cell adhesion
      molecule (EpCAM)(high)/CD44+ epithelial cells. Tumors originated from
      EpCAM(high)/CD44+ cells maintained a differentiated phenotype and reproduced the
      full morphologic and phenotypic heterogeneity of their parental lesions. Analysis
      of the surface molecule repertoire of EpCAM(high)/CD44+ cells led to the
      identification of CD166 as an additional differentially expressed marker, useful
      for CSC isolation in three of three CRC tested. These results validate the stem
      cell working model in human CRC and provide a highly robust surface marker
      profile for CRC stem cell isolation.

PMID- 17548815
TI  - Dissection of the components for PIP2 activation and thermosensation in TRP
      channels.
AB  - Phosphatidylinositol 4,5-bisphosphate (PIP2) plays a central role in the
      activation of several transient receptor potential (TRP) channels. The role of
      PIP2 on temperature gating of thermoTRP channels has not been explored in detail,
      and the process of temperature activation is largely unexplained. In this work,
      we have exchanged different segments of the C-terminal region between cold
      sensitive (TRPM8) and heat-sensitive (TRPV1) channels, trying to understand the
      role of the segment in PIP2 and temperature activation. A chimera in which the
      proximal part of the C-terminal of TRPV1 replaces an equivalent section of TRPM8
      C-terminal is activated by PIP2 and confers the phenotype of heat activation.
      PIP2, but not temperature sensitivity, disappears when positively charged
      residues contained in the exchanged region are neutralized. Shortening the
      exchanged segment to a length of 11 aa produces voltage-dependent and temperature
      insensitive channels. Our findings suggest the existence of different activation
      domains for temperature, PIP2, and voltage. We provide an interpretation for
      channel-PIP2 interaction using a full-atom molecular model of TRPV1 and PIP2
      docking analysis.

PMID- 17548816
TI  - Scm3, an essential Saccharomyces cerevisiae centromere protein required for G2/M
      progression and Cse4 localization.
AB  - A universal mark of centromeric chromatin is its packaging by a variant of
      histone H3 known as centromeric H3 (CenH3). The mechanism by which CenH3s are
      incorporated specifically into centromere DNA or the specialized function they
      serve there is not known. In a genetic approach to identify factors involved in
      CenH3 deposition, we screened for dosage suppressors of a temperature-sensitive
      cse4 allele in Saccharomyces cerevisiae (Cse4 is the S. cerevisiae CenH3).
      Independent screens yielded ORF YDL139C, which we named SCM3. Dosage suppression
      by SCM3 was specific for alleles affecting the histone fold domain of Cse4.
      Copurification and two-hybrid studies showed that Scm3 and Cse4 interact in vivo,
      and chromatin immunoprecipitation revealed that Scm3, like Cse4, is found
      associated with centromere DNA. Scm3 contains two essential protein domains, a
      Leu-rich nuclear export signal and a heptad repeat domain that is widely
      conserved in fungi. A conditional scm3 allele was generated to allow us to
      deplete Scm3. Upon Scm3 depletion, cells undergo a Mad2-dependent G2/M arrest,
      and centromere localization of Cse4 is perturbed. We suggest that S. cerevisiae
      Scm3 defines a previously undescribed family of fungal kinetochore proteins
      important for CenH3 localization.

PMID- 17548817
TI  - Central histamine H3 receptor signaling negatively regulates susceptibility to
      autoimmune inflammatory disease of the CNS.
AB  - Histamine (HA), a biogenic amine with a broad spectrum of activities in both
      physiological and pathological settings, plays a key regulatory role in
      experimental allergic encephalomyelitis, the autoimmune model of multiple
      sclerosis. HA exerts its effect through four G protein-coupled receptors
      designated HA receptor H1, H2, H3, and H4. We report here that, compared with
      wild-type animals, mice with a disrupted HA H3 receptor (H3RKO), the expression
      of which is normally confined to cells of the nervous system, develop more severe
      disease and neuroinflammation. We show that this effect is associated with
      dysregulation of blood-brain barrier permeability and increased expression of MIP
      2, IP-10, and CXCR3 by peripheral T cells. Our data suggest that pharmacological
      targeting of the H3R may be useful in preventing the development and formation of
      new lesions in multiple sclerosis, thereby significantly limiting the progression
      of the disease.

PMID- 17548818
TI  - Network structure of cerebral cortex shapes functional connectivity on multiple
      time scales.
AB  - Neuronal dynamics unfolding within the cerebral cortex exhibit complex spatial
      and temporal patterns even in the absence of external input. Here we use a
      computational approach in an attempt to relate these features of spontaneous
      cortical dynamics to the underlying anatomical connectivity. Simulating nonlinear
      neuronal dynamics on a network that captures the large-scale interregional
      connections of macaque neocortex, and applying information theoretic measures to
      identify functional networks, we find structure-function relations at multiple
      temporal scales. Functional networks recovered from long windows of neural
      activity (minutes) largely overlap with the underlying structural network. As a
      result, hubs in these long-run functional networks correspond to structural hubs.
      In contrast, significant fluctuations in functional topology are observed across
      the sequence of networks recovered from consecutive shorter (seconds) time
      windows. The functional centrality of individual nodes varies across time as
      interregional couplings shift. Furthermore, the transient couplings between brain
      regions are coordinated in a manner that reveals the existence of two
      anticorrelated clusters. These clusters are linked by prefrontal and parietal
      regions that are hub nodes in the underlying structural network. At an even
      faster time scale (hundreds of milliseconds) we detect individual episodes of
      interregional phase-locking and find that slow variations in the statistics of
      these transient episodes, contingent on the underlying anatomical structure,
      produce the transfer entropy functional connectivity and simulated blood
      oxygenation level-dependent correlation patterns observed on slower time scales.

PMID- 17548819
TI  - nanos gene control DNA mediates developmentally regulated transposition in the
      yellow fever mosquito Aedes aegypti.
AB  - Transposable elements (TEs) are proposed as a basis for developing drive systems
      to spread pathogen resistance genes through vector mosquito populations. The use
      of transcriptional and translational control DNA elements from genes expressed
      specifically in the insect germ line to mediate transposition offers
      possibilities for mitigating some of the concerns about transgene behavior in the
      target vector species and eliminating effects on nontarget organisms. Here, we
      describe the successful use of the promoter and untranslated regions from the
      nanos (nos) orthologous gene of the yellow fever mosquito, Aedes aegypti, to
      control sex- and tissue-specific expression of exogenously derived mariner MosI
      transposase-encoding DNA. Transgenic mosquitoes expressed transposase mRNA in
      abundance near or equal to the endogenous nos transcript and exclusively in the
      female germ cells. In addition, MosI mRNA was deposited in developing oocytes and
      localized and maintained at the posterior pole during early embryonic
      development. Importantly, four of five transgenic lines examined were capable of
      mobilizing a second MosI transgene into the mosquito genome, indicating that
      functional transposase was being produced. Thus, the nos control sequences show
      promise as part of a TE-based gene drive system.

PMID- 17548820
TI  - Load-dependent mechanism of nonmuscle myosin 2.
AB  - Loads on molecular motors regulate and coordinate their function. In a study that
      directly measures properties of internally strained myosin 2 heads bound to
      actin, we find that human nonmuscle myosins 2A and 2B show marked load-dependent
      changes in kinetics of ADP release but not in nucleotide binding. We show that
      the ADP release rate constant is increased 4-fold by the assisting load on one
      head and decreased 5-fold (for 2A) or 12-fold (for 2B) by the resisting load on
      the other. Thus these myosins, especially 2B, have marked mechanosensitivity of
      product release. By regulating the actin attachment of myosin heads, this
      provides a basis for energy-efficient tension maintenance without obstructing
      cellular contractility driven by other motors such as smooth muscle myosin.
      Whereas forward load accelerates the cycle of interaction with actin, resistive
      load increases duty ratio to favor tension maintenance by two-headed attachment.

PMID- 17548821
TI  - Structure of a receptor-binding fragment of reelin and mutational analysis reveal
      a recognition mechanism similar to endocytic receptors.
AB  - Reelin, a large secreted protein implicated in the cortical development of the
      mammalian brain, is composed of eight tandem concatenations of "reelin repeats"
      and binds to neuronal receptors belonging to the low-density lipoprotein receptor
      gene family. We found that both receptor-binding and subsequent Dab1
      phosphorylation occur solely in the segment spanning the fifth and sixth reelin
      repeats (R5-6). Monomeric fragment exhibited a suboptimal level of signaling
      activity and artificial oligomerization resulted in a 10-fold increase in
      activity, indicating the critical importance of higher-order multimerization in
      physiological reelin. A 2.0-A crystal structure from the R5-6 fragment revealed
      not only a unique domain arrangement wherein two repeats were aligned side by
      side with the same orientation, but also the unexpected presence of bound Zn
      ions. Structure-guided alanine mutagenesis of R5-6 revealed that two Lys residues
      (Lys-2360 and Lys-2467) constitute a central binding site for the low-density
      lipoprotein receptor class A module in the receptor, indicating a strong
      similarity to the ligand recognition mode shared among the endocytic lipoprotein
      receptors.

PMID- 17548822
TI  - Transient climate-carbon simulations of planetary geoengineering.
AB  - Geoengineering (the intentional modification of Earth's climate) has been
      proposed as a means of reducing CO2-induced climate warming while greenhouse gas
      emissions continue. Most proposals involve managing incoming solar radiation such
      that future greenhouse gas forcing is counteracted by reduced solar forcing. In
      this study, we assess the transient climate response to geoengineering under a
      business-as-usual CO2 emissions scenario by using an intermediate-complexity
      global climate model that includes an interactive carbon cycle. We find that the
      climate system responds quickly to artificially reduced insolation; hence, there
      may be little cost to delaying the deployment of geoengineering strategies until
      such a time as "dangerous" climate change is imminent. Spatial temperature
      patterns in the geoengineered simulation are comparable with preindustrial
      temperatures, although this is not true for precipitation. Carbon sinks in the
      model increase in response to geoengineering. Because geoengineering acts to mask
      climate warming, there is a direct CO2-driven increase in carbon uptake without
      an offsetting temperature-driven suppression of carbon sinks. However, this
      strengthening of carbon sinks, combined with the potential for rapid climate
      adjustment to changes in solar forcing, leads to serious consequences should
      geoengineering fail or be stopped abruptly. Such a scenario could lead to very
      rapid climate change, with warming rates up to 20 times greater than present-day
      rates. This warming rebound would be larger and more sustained should climate
      sensitivity prove to be higher than expected. Thus, employing geoengineering
      schemes with continued carbon emissions could lead to severe risks for the global
      climate system.

PMID- 17548824
TI  - Repeated sleep restriction in rats leads to homeostatic and allostatic responses
      during recovery sleep.
AB  - Recent studies indicate that chronic sleep restriction can have negative
      consequences for brain function and peripheral physiology and can contribute to
      the allostatic load throughout the body. Interestingly, few studies have examined
      how the sleep-wake system itself responds to repeated sleep restriction. In this
      study, rats were subjected to a sleep-restriction protocol consisting of 20 h of
      sleep deprivation (SD) followed by a 4-h sleep opportunity each day for 5
      consecutive days. In response to the first 20-h SD block on day 1, animals
      responded during the 4-h sleep opportunity with enhanced sleep intensity [i.e.,
      nonrapid eye movement (NREM) delta power] and increased rapid eye movement sleep
      time compared with baseline. This sleep pattern is indicative of a homeostatic
      response to acute sleep loss. Remarkably, after the 20-h SD blocks on days 2-5,
      animals failed to exhibit a compensatory NREM delta power response during the 4-h
      sleep opportunities and failed to increase NREM and rapid eye movement sleep
      times, despite accumulating a sleep debt each consecutive day. After losing
      approximately 35 h of sleep over 5 days of sleep restriction, animals regained
      virtually none of their lost sleep, even during a full 3-day recovery period.
      These data demonstrate that the compensatory/homeostatic sleep response to acute
      SD does not generalize to conditions of chronic partial sleep loss. We propose
      that the change in sleep-wake regulation in the context of repeated sleep
      restriction reflects an allostatic process, and that the allostatic load produced
      by SD has direct effects on the sleep-wake regulatory system.

PMID- 17548823
TI  - Major Caribbean and Central American frog faunas originated by ancient oceanic
      dispersal.
AB  - Approximately one-half of all species of amphibians occur in the New World
      tropics, which includes South America, Middle America, and the West Indies. Of
      those, 27% (801 species) belong to a large assemblage, the eleutherodactyline
      frogs, which breed out of water and lay eggs that undergo direct development on
      land. Their wide distribution and mode of reproduction offer potential for
      resolving questions in evolution, ecology, and conservation. However, progress in
      all of these fields has been hindered by a poor understanding of their
      evolutionary relationships. As a result, most of the species have been placed in
      a single genus, Eleutherodactylus, which is the largest among vertebrates. Our
      DNA sequence analysis of a major fraction of eleutherodactyline diversity
      revealed three large radiations of species with unexpected geographic isolation:
      a South American Clade (393 sp.), a Caribbean Clade (171 sp.), and a Middle
      American Clade (111 sp.). Molecular clock analyses reject the prevailing
      hypothesis that these frogs arose from land connections with North and South
      America and their subsequent fragmentation in the Late Cretaceous (80-70 Mya).
      Origin by dispersal, probably over water from South America in the early Cenozoic
      (47-29 million years ago, Mya), is more likely.

PMID- 17548825
TI  - Molecular dynamics using atomic-resolution structure reveal structural
      fluctuations that may lead to polymerization of human Cu-Zn superoxide dismutase.
AB  - Mutations of the gene encoding Cu-Zn superoxide dismutase (SOD1) cause 20% of the
      familial cases of the progressive neurodegenerative disease ALS. A growing body
      of evidence suggests that in familial ALS (FALS) it is the molecular behavior of
      the metal-depleted SOD1 dimer that leads to a gain of toxic properties by
      misfolding, unfolding, and aggregation. Structural studies have so far provided
      static snapshots on the behavior of the wild-type enzyme and some of the FALS
      mutants. New approaches are required to map out the structural trajectories of
      the molecule. Here, using our 1.15-A resolution structure of fully metallated
      human SOD1 and highly parallelized molecular dynamics code on a high-performance
      capability computer, we have undertaken molecular dynamics calculations to 4,000
      ps to reveal the first stages of misfolding caused by metal deletion. Large
      spatial and temporal fluctuations of the "electrostatic" and "Zn-binding" loops
      adjacent to the metal-binding sites are observed in the apo-enzyme relative to
      the fully metallated dimer. These early misfolding events expose the beta-barrels
      of the dimer to the external environment, allowing close interactions with
      adjacent molecules. Protection of the beta-edge of the protein can be partially
      restored by incorporating a single Zn molecule per dimer. These calculations
      reveal an essential step in the formation of the experimentally observed self
      aggregations of metal-depleted FALS mutant SOD1. This result also has
      implications for the role of demetallated wild-type SOD1 in sporadic cases of
      ALS, for which the molecular cause still remains undiscovered.

PMID- 17548826
TI  - Proteolysis of the barley receptor-like protein kinase RPG1 by a proteasome
      pathway is correlated with Rpg1-mediated stem rust resistance.
AB  - In plants, disease resistance mediated by the gene-for-gene mechanism involves
      the recognition of specific effector molecules produced by the pathogen either
      directly or indirectly by the resistance-gene products. This recognition triggers
      a series of signals, thereby serving as a molecular switch in regulating defense
      mechanisms by the plants. To understand the mechanism of action of the barley
      stem rust resistance gene Rpg1, we investigated the fate of the RPG1 protein in
      response to infection with the stem rust fungus, Puccinia graminis f. sp.
      tritici. The investigations revealed that RPG1 disappears to undetectable limits
      only in the infected tissues in response to avirulent, but not virulent
      pathotypes. The RPG1 protein disappearance is rapid and appears to be due to
      specific protein degradation via the proteasome-mediated pathway as indicated by
      inhibition with the proteasomal inhibitor MG132, but not by other protease
      inhibitors.

PMID- 17548827
TI  - Synthesis of C5-dicarboxylic acids from C2-units involving crotonyl-CoA
      carboxylase/reductase: the ethylmalonyl-CoA pathway.
AB  - Fifty years ago, Kornberg and Krebs established the glyoxylate cycle as the
      pathway for the synthesis of cell constituents from C2-units. However, since
      then, many bacteria have been described that do not contain isocitrate lyase, the
      key enzyme of this pathway. Here, a pathway termed the ethylmalonyl-CoA pathway
      operating in such organisms is described. Isotopically labeled acetate and
      bicarbonate were transformed to ethylmalonyl-CoA by cell extracts of acetate
      grown, isocitrate lyase-negative Rhodobacter sphaeroides as determined by NMR
      spectroscopy. Crotonyl-CoA carboxylase/reductase, catalyzing crotonyl-CoA + CO2 +
      NADPH --> ethylmalonyl-CoA- + NADP+ was identified as the key enzyme of the
      ethylmalonyl-CoA pathway. The reductive carboxylation of an enoyl-thioester is a
      unique biochemical reaction, unprecedented in biology. The enzyme from R.
      sphaeroides was heterologously produced in Escherichia coli and characterized.
      Crotonyl-CoA carboxylase/reductase (or its gene) can be used as a marker for the
      presence of the ethylmalonyl-CoA pathway, which functions not only in acetyl-CoA
      assimilation. In Streptomyces sp., it may also supply precursors (ethylmalonyl
      CoA) for antibiotic biosynthesis. For methylotrophic bacteria such as
      Methylobacterium extorquens, extension of the serine cycle with reactions of the
      ethylmalonyl-CoA pathway leads to a simplified scheme for isocitrate lyase
      independent C1 assimilation.

PMID- 17548828
TI  - Raising plasma fatty acid concentration induces increased biogenesis of
      mitochondria in skeletal muscle.
AB  - A number of studies have reported that a high-fat diet induces increases in
      mitochondrial fatty acid oxidation enzymes in muscle. In contrast, in two recent
      studies raising plasma free fatty acids (FFA) resulted in a decrease in
      mitochondria. In this work, we reevaluated the effects of raising FFA on muscle
      mitochondrial biogenesis and capacity for fat oxidation. Rats were fed a high-fat
      diet and given daily injections of heparin to raise FFA. This treatment induced
      an increase in mitochondrial biogenesis in muscle, as evidenced by increases in
      mitochondrial enzymes of the fatty acid oxidation pathway, citrate cycle, and
      respiratory chain, with an increase in the capacity to oxidize fat, as well as an
      increase in mitochondrial DNA copy number. Raising FFA also resulted in an
      increase in binding of peroxisome proliferator-activated receptor (PPAR) delta to
      the PPAR response element on the carnitine palmitoyltransferase 1 promoter. We
      interpret our results as evidence that raising FFA induces an increase in
      mitochondrial biogenesis in muscle by activating PPARdelta.

PMID- 17548829
TI  - On the ability of the Viking gas chromatograph-mass spectrometer to detect
      organic matter.
AB  - A recent paper by Navarro-Gonzalez et al. [Navarro-Gonzalez R, Navarro KF, de la
      Rosa J, Iniguez E, Molina P, Miranda LD, Morales P, Cienfuegos E, Coll P, Raulin
      F, et al. (2006) Proc Natl Acad Sci USA 103:16089-16094] claims to show that the
      Viking GCMS (gas chromatograph-mass spectrometer) experiment, which carried out a
      search for organic matter at the surface of Mars in 1976, "may have been blind to
      low levels of organics." To rebut this assertion, the Viking experiment, test
      data, and results on Mars are reviewed, and the fallacies in the design,
      execution, and interpretation of the new experiments presented by Navarro
      Gonzalez et al. are critically examined.

PMID- 17548830
TI  - Cross-peak-specific two-dimensional electronic spectroscopy.
AB  - Intermolecular electronic coupling dictates the optical properties of molecular
      aggregate systems. Of particular interest are photosynthetic pigment-protein
      complexes that absorb sunlight then efficiently direct energy toward the
      photosynthetic reaction center. Two-dimensional (2D) ultrafast spectroscopy has
      been used widely in the infrared (IR) and increasingly in the visible to probe
      excitonic couplings and observe dynamics, but the off-diagonal spectral
      signatures of coupling are often obscured by broad diagonal peaks, especially in
      the visible regime. Rotating the polarizations of the laser pulses exciting the
      sample can highlight certain spectral features, and the use of polarized pulse
      sequences to elucidate cross-peaks in 2D spectra has been demonstrated in the IR
      for vibrational transitions. Here we develop 2D electronic spectroscopy using
      cross-peak-specific pulse polarization conditions in an investigation of the
      Fenna-Matthews-Olson light harvesting complex from green photosynthetic bacteria.
      Our measurements successfully highlight off-diagonal features of the 2D spectra
      and, in combination with an analysis based on the signs of features arising from
      particular energy level pathways and theoretical simulation, we characterize the
      dominant response pathways responsible for the spectral features. Cross-peak
      specific 2D electronic spectroscopy provides insight into the interchromophore
      couplings, as well as into the energetic pathways giving rise to the signal. With
      femtosecond resolution, we also observe dynamical processes that depend on these
      couplings and interactions with the protein environment.

PMID- 17548831
TI  - Trophic cascades triggered by overfishing reveal possible mechanisms of ecosystem
      regime shifts.
AB  - Large-scale transitions between alternative states in ecosystems are known as
      regime shifts. Once described as healthy and dominated by various marine
      predators, the Black Sea ecosystem by the late 20th century had experienced
      anthropogenic impacts such as heavy fishing, cultural eutrophication, and
      invasions by alien species. We studied changes related to these "natural
      experiments" to reveal the mechanisms of regime shifts. Two major shifts were
      detected, the first related to a depletion of marine predators and the second to
      an outburst of the alien comb jelly Mnemiopsis leidyi; both shifts were triggered
      by intense fishing resulting in system-wide trophic cascades. The complex nature
      of ecosystem responses to human activities calls for more elaborate approaches
      than currently provided by traditional environmental and fisheries management.
      This implies challenging existing practices and implementing explanatory models
      of ecosystem interactions that can better reconcile conservation and ecosystem
      management ideals.

PMID- 17548832
TI  - Pesticides reduce symbiotic efficiency of nitrogen-fixing rhizobia and host
      plants.
AB  - Unprecedented agricultural intensification and increased crop yield will be
      necessary to feed the burgeoning world population, whose global food demand is
      projected to double in the next 50 years. Although grain production has doubled
      in the past four decades, largely because of the widespread use of synthetic
      nitrogenous fertilizers, pesticides, and irrigation promoted by the "Green
      Revolution," this rate of increased agricultural output is unsustainable because
      of declining crop yields and environmental impacts of modern agricultural
      practices. The last 20 years have seen diminishing returns in crop yield in
      response to increased application of fertilizers, which cannot be completely
      explained by current ecological models. A common strategy to reduce dependence on
      nitrogenous fertilizers is the production of leguminous crops, which fix
      atmospheric nitrogen via symbiosis with nitrogen-fixing rhizobia bacteria, in
      rotation with nonleguminous crops. Here we show previously undescribed in vivo
      evidence that a subset of organochlorine pesticides, agrichemicals, and
      environmental contaminants induces a symbiotic phenotype of inhibited or delayed
      recruitment of rhizobia bacteria to host plant roots, fewer root nodules
      produced, lower rates of nitrogenase activity, and a reduction in overall plant
      yield at time of harvest. The environmental consequences of synthetic chemicals
      compromising symbiotic nitrogen fixation are increased dependence on synthetic
      nitrogenous fertilizer, reduced soil fertility, and unsustainable long-term crop
      yields.

PMID- 17548833
TI  - Huntingtin facilitates dynein/dynactin-mediated vesicle transport.
AB  - Cytoplasmic dynein is a multisubunit microtubule motor complex that, together
      with its activator, dynactin, drives vesicular cargo toward the minus ends of
      microtubules. Huntingtin (Htt) is a vesicle-associated protein found in both
      neuronal and nonneuronal cells that is thought to be involved in vesicular
      transport. In this study, we demonstrate through yeast two-hybrid and affinity
      chromatography assays that Htt and dynein intermediate chain interact directly;
      endogenous Htt and dynein co-immunoprecipitate from mouse brain cytosol. Htt RNAi
      in HeLa cells results in Golgi disruption, similar to the effects of compromising
      dynein/dynactin function. In vitro studies reveal that Htt and dynein are both
      present on vesicles purified from mouse brain. Antibodies to Htt inhibited
      vesicular transport along microtubules, suggesting that Htt facilitates dynein
      mediated vesicle motility. In vivo inhibition of dynein function results in a
      significant redistribution of Htt to the cell periphery, suggesting that dynein
      transports Htt-associated vesicles toward the cell center. Together these
      findings indicate that Htt binds to dynein and acts in a complex along with
      dynactin and Htt-associated protein-1 to facilitate vesicular transport.

PMID- 17548834
TI  - Intrinsic dephasing in one-dimensional ultracold atom interferometers.
AB  - Quantum-phase fluctuations prevent true long-range phase order from forming in
      interacting 1D condensates, even at zero temperature. Nevertheless, by
      dynamically splitting the condensate into two parallel decoupled tubes the system
      can be prepared with a macroscopic relative phase, facilitating interferometric
      measurement. Here, we describe a dephasing mechanism whereby the quantum-phase
      fluctuations, which are so effective in equilibrium, act to destroy the
      macroscopic relative phase that was imposed as a nonequilibrium initial
      condition. We show that the phase coherence between the condensates decays
      exponentially with a dephasing time that depends on intrinsic parameters: the
      interaction strength, sound velocity, and density. Interestingly, significant
      temperature dependence appears only above a cross-over scale T*. In contrast to
      the usual phase diffusion, which is essentially an effect of confinement and
      leads to Gaussian decay, the exponential dephasing caused by fluctuations is a
      bulk effect that survives the thermodynamic limit.

PMID- 17548835
TI  - Fragile X mental retardation protein FMRP and the RNA export factor NXF2
      associate with and destabilize Nxf1 mRNA in neuronal cells.
AB  - Fragile X syndrome is caused by the inactivation of the X-linked FMR1 gene,
      leading to the loss of its encoded protein FMRP. Although macroorchidism and
      defects in neuronal architecture and function have been associated with lack of
      FMRP, the exact molecular mechanism underlying this disease remains unclear. We
      have reported previously that in the brain and testis of mice, FMRP specifically
      interacts with a distinct mRNA nuclear export factor NXF2 but not with its close
      relative NXF1, a ubiquitously expressed essential mRNA nuclear export factor.
      This interaction marked NXF2 as a putative functional partner of FMRP. Here, we
      demonstrate by immunoprecipitation and quantitative real-time RT-PCR that, in
      cultured mouse neuronal cells, both FMRP and NXF2 are present in Nxf1 mRNA
      containing ribonucleoprotein particles. Further, we show that expression of NXF2
      leads to the destabilization of Nxf1 mRNA and that this effect is abolished when
      Fmr1 expression is reduced by siRNA, arguing that both proteins collaborate to
      exert this effect. Importantly, these findings correlate well with our
      observations that in both mouse hippocampal neurons and male germ cells where the
      expression of FMRP and NXF2 is most prominent, the expression of NXF1 is
      relatively poorly expressed. Our studies thus identify Nxf1 mRNA as a likely
      biologically relevant in vivo target of both FMRP and NXF2 and implicate FMRP, in
      conjunction with NXF2, as a posttranscriptional regulator of a major mRNA export
      factor. Such regulation may prove important in the normal development and
      function of neurons as well as of male germ cells.

PMID- 17548836
TI  - Bone morphogenetic protein 1 processes prolactin to a 17-kDa antiangiogenic
      factor.
AB  - In addition to classical expression patterns in pituitary and placenta and
      functions in growth and reproduction, members of the small family of hormones
      that includes prolactin (PRL), growth hormone (GH), and placental lactogen are
      expressed by endothelia and have angiogenic effects. In contrast, 16- to 17-kDa
      proteolytic fragments of these hormones have antiangiogenic effects. Here we show
      that PRL and GH are bound and processed by members of the bone morphogenetic
      protein 1 (BMP1) subgroup of extracellular metalloproteinases, previously shown
      to play key roles in forming extracellular matrix and in activating certain
      TGFbeta superfamily members. BMP1 has previously been suggested to play roles in
      angiogenesis, as high throughput screens have found its mRNA to be one of those
      induced to highest levels in tumor-associated endothelia compared with resting
      endothelia. PRL and GH cleavage is shown to occur in each hormone at a single
      site typical of sites previously characterized in known substrates of BMP1-like
      proteinases, and the approximately 17-kDa PRL N-terminal fragment so produced is
      demonstrated to have potent antiangiogenic activity. Mouse embryo fibroblasts are
      shown to produce both PRL and GH and to process them to approximately 17-kDa
      forms, whereas GH and PRL processing activity is lost in mouse embryo fibroblasts
      doubly null for two genes encoding BMP1-like proteinases.

PMID- 17548837
TI  - To screen or not to screen older women for breast cancer: a new twist on an old
      question or will we ever invest in getting the answers?

PMID- 17548838
TI  - Mammography surveillance and mortality in older breast cancer survivors.
AB  - PURPOSE: There are more than 2,000,000 breast cancer survivors in the United
      States today. While surveillance for asymptomatic recurrence and second primary
      is included in consensus recommendations, the effectiveness of this surveillance
      has not been well characterized. Our purpose is to estimate the effectiveness of
      surveillance mammography in a cohort of breast cancer survivors with complete
      ascertainment of surveillance mammograms and negligible losses to follow-up.
      PATIENTS AND METHODS: We enrolled 1,846 stage I and II breast cancer patients who
      were at least 65 years old at six integrated health care delivery systems. We
      used medical record review and existing databases to ascertain patient, tumor,
      and therapy characteristics, as well as receipt of surveillance mammograms. We
      linked personal identifiers to the National Death Index to ascertain date and
      cause of death. We matched four controls to each breast cancer decedent to
      estimate the association between receipt of surveillance mammogram and breast
      cancer mortality. RESULTS: One hundred seventy-eight women died of breast cancer
      during 5 years of follow-up. Each additional surveillance mammogram was
      associated with a 0.69-fold decrease in the odds of breast cancer mortality (95%
      CI, 0.52 to 0.92). The protective association was strongest among women with
      stage I disease, those who received mastectomy, and those in the oldest age
      group. CONCLUSION: Given existing recommendations for post-therapy surveillance,
      trials to compare surveillance with no surveillance are unlikely. This large
      observational study provides support for the recommendations, suggesting that
      receipt of surveillance mammograms reduces the rate of breast cancer mortality in
      older patients diagnosed with early-stage disease.

PMID- 17548839
TI  - Phase III study of capecitabine plus oxaliplatin compared with continuous
      infusion fluorouracil plus oxaliplatin as first-line therapy in metastatic
      colorectal cancer: final report of the Spanish Cooperative Group for the
      Treatment of Digestive Tumors Trial.
AB  - PURPOSE: The aim of this phase III trial was to compare the efficacy and safety
      of capecitabine plus oxaliplatin (XELOX) versus Spanish-based continuous-infusion
      high-dose fluorouracil (FU) plus oxaliplatin (FUOX) regimens as first-line
      therapy for metastatic colorectal cancer (MCRC). PATIENTS AND METHODS: A total of
      348 patients were randomly assigned to receive XELOX (oral capecitabine 1,000
      mg/m2 bid for 14 days plus oxaliplatin 130 mg/m2 on day 1 every 3 weeks) or FUOX
      (continuous-infusion FU 2,250 mg/m2 during 48 hours on days 1, 8, 15, 22, 29, and
      36 plus oxaliplatin 85 mg/m2 on days 1, 15, and 29 every 6 weeks). RESULTS: There
      were no significant differences in efficacy between XELOX and FUOX arms, which
      showed, respectively, median time to tumor progression (TTP; 8.9 v 9.5 months; P
      = .153); median overall survival (18.1 v 20.8 months; P = .145); and confirmed
      response rate (RR; 37% v 46%; P = .539). The safety profile of the two regimens
      was similar, although there were lower rates of grade 3/4 diarrhea (14% v 24%)
      and grade 1/2 stomatitis (28% v 43%), and higher rates of grade 1/2
      hyperbilirubinemia (37% v 21%) and grade 1/2 hand-foot syndrome (14% v 5%) with
      XELOX versus FUOX, respectively. CONCLUSION: This randomized study shows a
      similar TTP of XELOX compared with FUOX in the first-line treatment of MCRC,
      although there was a trend for slightly lower RR and survival. XELOX can be
      considered as an alternative to FUOX.

PMID- 17548840
TI  - Phase III study of capecitabine plus oxaliplatin compared with fluorouracil and
      leucovorin plus oxaliplatin in metastatic colorectal cancer: a final report of
      the AIO Colorectal Study Group.
AB  - PURPOSE: To compare the use of capecitabine plus oxaliplatin (CAPOX) with
      infusional fluorouracil (FU)/folinic acid plus oxaliplatin (FUFOX) as first-line
      therapy for patients with metastatic colorectal cancer (MCRC). PATIENTS AND
      METHODS: A total of 474 patients with MCRC received either CAPOX (capecitabine
      1,000 mg/m2 bid, days 1 to 14 plus oxaliplatin 70 mg/m2 days 1 and 8, repeated
      every 22 days) ) or FUFOX (oxaliplatin 50 mg/m2 followed by leucovorin 500 mg/m2
      plus FU 2,000 mg/m2 as a 22-hour infusion days 1, 8, 15, and 22, repeated every
      36 days). The primary end point was progression-free survival (PFS). Secondary
      end points were response rate (RR), overall survival (OS), time to treatment
      failure, and toxicity. The study was designed to determine noninferiority for the
      CAPOX regimen. RESULTS: Median PFS was 7.1 months in the CAPOX arm and 8.0 months
      in the FUFOX arm (hazard ratio [HR], 1.17; 95% CI, 0.96 to 1.43; P = .117).
      Median OS was 16.8 months (CAPOX) and 18.8 months (FUFOX; HR, 1.12; 95% CI, 0.92
      to 1.38; P = .26). Overall RRs were 48% for CAPOX (95% CI, 41% to 54%) and 54%
      for FUFOX (95% CI, 47% to 60%). Both regimens were generally well tolerated,
      although there was a significantly higher incidence of grade 2/3 hand-foot
      syndrome (HFS) in the CAPOX arm (P = .028). CONCLUSION: CAPOX resulted in a
      slightly inferior efficacy than FUFOX. With respect to PFS, the best estimate of
      the HR of 1.17 was within the prespecified equivalence range. However, a relevant
      inferiority cannot be excluded. Both regimens were generally well tolerated but
      there was a significantly higher rate of grade 2/3 HFS in the CAPOX arm.

PMID- 17548841
TI  - Plasma testosterone and prognosis of postmenopausal breast cancer patients.
AB  - PURPOSE: High endogenous testosterone is associated with increased breast cancer
      (BC) risk. We designed this study specifically to assess the long-term prognostic
      role of testosterone in a cohort of postmenopausal BC patients. PATIENTS AND
      METHODS: We considered 194 postmenopausal women, operated on for early BC (T1
      2N0M0), who never received chemotherapy or hormonal therapy, and who participated
      in a fenretinide BC prevention trial as untreated controls. Blood samples were
      collected 3 months (median) after surgery; plasma samples, stored at -80 degrees
      C, were radioimmunoassayed for testosterone. Median follow-up was 14 years. The
      main end point was any cancer event. Event-free survival was estimated by the
      Kaplan-Meier method. Hazard ratios (HRs) of events by testosterone level were
      estimated by the Cox model, adjusting for age, tumor size, and histology.
      RESULTS: Patients with high testosterone (> or = 0.40 ng/mL, median of
      distribution) had significantly lower event-free survival than those with low
      testosterone (log-rank P = .004). The adjusted HR of patients with high versus
      low testosterone was 2.05 (95% CI, 1.28 to 3.27). High testosterone was also
      associated with a significantly higher risk of BC events (relapse and second
      primary) with an adjusted HR of 1.77 (95% CI, 1.06 to 2.96). Eleven second
      primaries (non-BC) occurred in the high-testosterone group, four in the low
      testosterone group. CONCLUSION: High plasma testosterone strongly predicts poorer
      prognosis in postmenopausal BC patients not administered adjuvant therapy.
      Testosterone levels should be determined as part of the prognostic work-up.

PMID- 17548842
TI  - Current issues in the classification of psychotic major depression.
AB  - Depression is one of the most common mental disorders worldwide. There are a
      number of depression subtypes, and there has been much debate about how to most
      accurately capture and organize the features and subtypes of major depression. We
      review the current state of categorizing unipolar major depression with psychotic
      features (psychotic major depression, PMD), including clinical, biological, and
      treatment aspects of the disorder. We then propose some improvements to the
      current unipolar major depression categorization system. Finally, we identify
      important issues in need of further research to help elucidate the subtype of
      unipolar PMD.

PMID- 17548843
TI  - Supportive therapy for schizophrenia.

PMID- 17548844
TI  - Deconstructing Psychosis conference February 2006: the validity of schizophrenia
      and alternative approaches to the classification of psychosis.
AB  - The DSM V planning process is currently underway and it has once again ignited
      the debate about the validity of the schizophrenia diagnosis. In this paper, we
      review the psychometric literature examining the evidence for discontinuity
      between schizophrenia and normality and the distinction between schizophrenia and
      other psychotic disorders. We conclude by proposing potential alternative
      approaches to refining the classification of psychosis.

PMID- 17548846
TI  - Competing demands or clinical inertia: the case of elevated glycosylated
      hemoglobin.
AB  - PURPOSE: This study aimed to examine the contribution of competing demands to
      changes in hypoglycemic medications and to return appointment intervals for
      patients with type 2 diabetes and an elevated glycosylated hemoglobin (A1c)
      level. METHODS: We observed 211 primary care encounters by adult patients with
      type 2 diabetes in 20 primary care clinics and documented changes in hypoglycemic
      medications. Competing demands were assessed from length of encounter, number of
      concerns patients raised, and number of topics brought up by the clinician. Days
      to the next scheduled appointment were obtained at patient checkout. Recent A1c
      values and dates were determined from the chart. RESULTS: Among patients with an
      A(1c) level greater than 7%, each additional patient concern was associated with
      a 49% (95% confidence interval, 35%-60%) reduction in the likelihood of a change
      in medication, independent of length of the encounter and most recent level of
      A1c. Among patients with an A(1c) level greater than 7% and no change in
      medication, for every additional minute of encounter length, the time to the next
      scheduled appointment decreased by 2.8 days (P = .001). Similarly, for each
      additional 1% increase in A1c level, the time to the next scheduled appointment
      decreased by 8.6 days (P=.001). CONCLUSIONS: The concept of clinical inertia is
      limited and does not fully characterize the complexity of primary care
      encounters. Competing demands is a principle for constructing models of primary
      care encounters that are more congruent with reality and should be considered in
      the design of interventions to improve chronic disease outcomes in primary care
      settings.

PMID- 17548845
TI  - Deconstructing psychosis with human brain imaging.
AB  - This review synthesizes our current knowledge on the neurobiology of psychosis
      from an array of in vivo brain-imaging studies. The evidence base consists of
      hundreds of studies of patients with schizophrenia and fewer on bipolar disorder
      but rarely providing direct comparisons between the disorders or integration
      across methods. Replicated findings in schizophrenia include reduced whole-brain
      and hippocampal volume as potential vulnerability markers, with further
      progression at onset; reduced N-acetyl aspartate concentrations in hippocampus
      and prefrontal cortex; striatal dopamine D(2) receptors upregulation; and
      alteration in the relation between frontal and temporal activation. These
      findings are not attributable to medication effects but are of unclear
      specificity and may apply across the psychosis spectrum. There are consistently
      replicated associations of psychotic symptoms and cognitive impairment in both
      structural and functional imaging in schizophrenia but not, as yet, in bipolar
      disorder. Therefore, it would be premature to dispense with current diagnostic
      categories because direct comparisons among them are rare, insufficient studies
      have examined longitudinal changes, and long-term imaging outcome studies in
      first-episode psychosis have not yet been done. To address these issues and make
      neuroimaging "clinically relevant," investigators will need to standardize their
      approaches to data acquisition and analysis, and construct the necessary range of
      "human brain maps," to implement studies that are sufficiently powered to provide
      reliable data pertinent to deconstructing psychosis.

PMID- 17548847
TI  - Acanthosis nigricans and diabetes risk factors: prevalence in young persons seen
      in southwestern US primary care practices.
AB  - PURPOSE: Evidence shows acanthosis nigricans is often associated with
      hyperinsulinemia and may indicate increased risk of type 2 diabetes mellitus. The
      purpose of this study was to determine the association of acanthosis nigricans
      with type 2 diabetes risk factors and disease in young persons. METHODS: We
      conducted a cross-sectional study in the Research in Outpatient Settings Network,
      a practice-based research network in southwestern US communities. Participating
      clinicians (N = 96) collected data on children and young adults aged 7 to 39
      years seen during a 2-week sampling period. The main outcomes were the prevalence
      of acanthosis nigricans, type 2 diabetes risk factors (ethnicity, family history
      of type 2 diabetes, hypertension, overweight/obesity), type 2 diabetes, and the
      relationships among these. RESULTS: Among 1,133 patients sampled, risk factors
      for type 2 diabetes were common: 69% had a family history of the disease; 3% of
      children (aged 7 to 19 years) and 12% of adults had hypertension; 43% of children
      and 73% of adults were overweight or obese; and 80% were members of ethnic
      minorities. Acanthosis nigricans was found in 17% of children and 21% of adults.
      Among children and adults alike, the more type 2 diabetes risk factors that were
      present, the higher the prevalence of acanthosis nigricans (P <.001). The
      prevalence ratio for type 2 diabetes in patients with acanthosis nigricans was
      1.97 (95% confidence interval, 1.18-3.27; P = .01) after controlling for age,
      body mass index, and the number of type 2 diabetes risk factors. Clinicians
      reported that the identification of acanthosis nigricans frequently led to
      discussions about lifestyle modification for decreasing the risk of type 2
      diabetes. CONCLUSIONS: Patients with acanthosis nigricans are likely to have
      multiple risk factors for type 2 diabetes. Acanthosis nigricans may be an
      independent risk factor for this disease. Detection of acanthosis nigricans may
      help clinicians more rapidly identify high-risk individuals for diabetes
      counseling.

PMID- 17548848
TI  - Electronic medical records and diabetes quality of care: results from a sample of
      family medicine practices.
AB  - PURPOSE: Care of patients with diabetes requires management of complex clinical
      information, which may be improved by the use of an electronic medical record
      (EMR); however, the actual relationship between EMR usage and diabetes care
      quality in primary care settings is not well understood. We assessed the
      relationship between EMR usage and diabetes care quality in a sample of family
      medicine practices. METHODS: We conducted cross-sectional analyses of baseline
      data from 50 practices participating in a practice improvement study. Between
      April 2003 and December 2004 chart auditors reviewed a random sample of medical
      records from patients with diabetes in each practice for adherence to guidelines
      for diabetes processes of care, treatment, and achievement of intermediate
      outcomes. Practice leaders provided medical record system information. We
      conducted multivariate analyses of the relationship between EMR usage and
      diabetes care adjusting for potential practice- and patient-level confounders and
      practice-level clustering. RESULTS: Diabetes care quality in all practices showed
      room for improvement; however, after adjustment, patient care in the 37 practices
      not using an EMR was more likely to meet guidelines for process (odds ratio [OR],
      2.25; 95% confidence interval [CI], 1.42-3.57) treatment (OR, 1.67; 95% CI, 1.07
      2.60), and intermediate outcomes (OR, 2.68; 95% CI, 1.49-4.82) than in the 13
      practices using an EMR. CONCLUSIONS: The use of an EMR in primary care practices
      is insufficient for insuring high-quality diabetes care. Efforts to expand EMR
      use should focus not only on improving technology but also on developing methods
      for implementing and integrating this technology into practice reality.

PMID- 17548849
TI  - Sufficiently important difference for common cold: severity reduction.
AB  - PURPOSE: We undertook a study to estimate the sufficiently important difference
      (SID) for the common cold. The SID is the smallest benefit that an intervention
      would require to justify costs and risks. METHODS: Benefit-harm tradeoff
      interviews (in-person and telephone) assessed SID in terms of overall severity
      reduction using evidence-based simple-language scenarios for 4 common cold
      treatments: vitamin C, the herbal medicine echinacea, zinc lozenges, and the
      unlicensed antiviral pleconaril. RESULTS: Response patterns to the 4 scenarios in
      the telephone and in-person samples were not statistically distinguishable and
      were merged for most analyses. The scenario based on vitamin C led to a mean SID
      of 25% (95% confidence interval [CI] 0.23-0.27). For the echinacea-based
      scenario, mean SID was 32% (95% CI, 0.30-0.34). For the zinc-based scenario, mean
      SID was 47% (95% CI, 0.43-0.51). The scenario based on preliminary antiviral
      trials provided a mean SID of 57% (95% CI, 0.53-0.61). Multivariate analyses
      suggested that (1) between-scenario differences were substantive and reproducible
      in the 2 samples, (2) presence or severity of illness did not predict SID, and
      (3) SID was not influenced by age, sex, tobacco use, ethnicity, income, or
      education. Despite consistencies supporting the model and methods, response
      patterns were diverse, with wide spreads of individual SID values within and
      among treatment scenarios. CONCLUSIONS: Depending on treatment specifics, people
      want an on-average 25% to 57% reduction in overall illness severity to justify
      costs and risks of popular cold treatments. Randomized trial evidence does not
      support benefits this large. This model and these methods should be further
      developed for use in other disease entities.

PMID- 17548850
TI  - Home visiting for adolescent mothers: effects on parenting, maternal life course,
      and primary care linkage.
AB  - PURPOSE: Adolescent mothers are at risk for rapidly becoming pregnant again and
      for depression, school dropout, and poor parenting. We evaluated the impact of a
      community-based home-visiting program on these outcomes and on linking the
      adolescents with primary care. METHODS: Pregnant adolescents aged 12 to 18 years,
      predominantly with low incomes and of African American race, were recruited from
      urban prenatal care sites and randomly assigned to home visiting or usual care.
      Trained home visitors, recruited from local communities, were paired with each
      adolescent and provided services through the child's second birthday. They
      delivered a parenting curriculum, encouraged contraceptive use, connected the
      teen with primary care, and promoted school continuation. Research assistants
      collected data via structured interviews at baseline and at 1 and 2 years of
      follow-up using validated instruments to measure parenting (Adult-Adolescent
      Parenting Inventory) and depression (Center for Epidemiologic Studies
      Depression). School status and repeat pregnancy were self-reported. We measured
      program impact over time with intention-to-treat analyses using generalized
      estimating equations (GEE). RESULTS: Of 122 eligible pregnant adolescents, 84
      consented, completed baseline assessments, and were randomized to a home-visited
      group (n = 44) or a control group (n = 40). Eighty-three percent completed year 1
      or year 2 follow-up assessments, or both. With GEE, controlling for baseline
      differences, follow-up parenting scores for home-visited teens were 5.5 points
      higher than those for control teens (95% confidence interval, 0.5-10.4 points; P
      = .03) and their adjusted odds of school continuation were 3.5 times greater (95%
      confidence interval, 1.1-11.8; P <.05). The program did not have any impact on
      repeat pregnancy, depression, or linkage with primary care. CONCLUSIONS: This
      community-based home-visiting program improved adolescent mothers' parenting
      attitudes and school continuation, but it did not reduce their odds of repeat
      pregnancy or depression or achieve coordination with primary care. Coordinated
      care may require explicit mechanisms to promote communication between the
      community program and primary care.

PMID- 17548851
TI  - Different paths to high-quality care: three archetypes of top-performing practice
      sites.
AB  - PURPOSE: Primary care practices use different approaches in their quest for high
      quality care. Previous work in the Practice Partner Research Network (PPRNet)
      found that improved outcomes are associated with strategies to prioritize
      performance, involve staff, redesign elements of the delivery system, make
      patients active partners in guideline adherence, and use tools embedded in the
      electronic medical record. The aim of this study was to examine variations in the
      adoption of improvements among sites achieving the best outcomes. METHODS: This
      study used an observational case study design. A practice-level measure of
      adherence to clinical guidelines was used to identify the highest performing
      practices in a network of internal and family medicine practices participating in
      a national demonstration project. We analyzed qualitative and quantitative
      information derived from project documents, field notes, and evaluation
      questionnaires to develop and compare case studies. RESULTS: Nine cases are
      described. All use many of the same improvement strategies. Differences in the
      way improvements are organized define 3 distinct archetypes: the Technophiles,
      the Motivated Team, and the Care Enterprise. There is no single approach that
      explains the superior performance of high-performing practices, though each has
      adopted variations of PPRNet's improvement model. CONCLUSIONS: Practices will
      vary in their path to high-quality care. The archetypes could prove to be a
      useful guide to other practices selecting an overall quality improvement
      approach.

PMID- 17548852
TI  - A national survey of primary care practice-based research networks.
AB  - PURPOSE: Increasing numbers of primary care practice-based research networks
      (PBRNs) are being developed in the United States to perform research relevant to
      everyday practice. To assess the current status and potential value of this
      resource, we surveyed US primary care PBRNs in operation from late 2003 to early
      2004. METHODS: We performed a Web-based survey and structured interviews with
      PBRN directors and administrative officers, assessing PBRNs' history, size,
      location, organization, resources, operations, and productivity (funding
      obtained, studies performed, and articles published). RESULTS: Of 111 primary
      care PBRNs identified, 89 (80%) responded to the survey. The 86 (77%) meeting the
      criteria for primary care PBRNs contained 1,871 practices, 12,957 physicians
      (mean 152 per PBRN, median 100), and 14.7 million patients (mean 229,880 per
      PBRN, median 105,000). Minority and underinsured patients were overrepresented.
      The average PBRN was young (4.4 +/- 5.7 years): one-half had performed 3 or fewer
      studies. Three-quarters were affiliated with universities. Common research foci
      included prevention, diabetes, cardiovascular risk factors, and mental health.
      Respondent PBRNs had published more than 600 articles in peer-reviewed journals.
      PBRNs studying questions posed by outside researchers had more federal funding
      (84% vs 27%, P=.006). PBRNs citing funding as a weakness relied more on local
      resources to fund research projects (70% vs 40%, P=.036). CONCLUSIONS: American
      primary care PBRNs are mainly young, diverse, and pursuing a variety of research
      foci. Most have university links and provide a dynamic town-gown relationship
      that could be a vital national resource for improving primary care, translating
      research into practice, and meeting the National Institutes of Health Roadmap
      goals. PBRNs merit further attention from both private and public funding
      agencies and researchers interested in studying the delivery of primary care.

PMID- 17548853
TI  - Improving medical practice: a conceptual framework.
AB  - PURPOSE: The purpose of this article is to produce a relatively simple conceptual
      framework for guiding and studying practice improvement. METHODS: I summarize the
      lessons from my experience with a variety of quality improvement research studies
      during the last 30 years, supplemented with relevant literature from both
      medicine and other industries about the issues associated with successful quality
      improvement. RESULTS: My experience suggests that organizational leadership with
      an urgent vision for change, ability to manage the change process, and selection
      of systematic changes capable of fulfilling the vision are each critical for
      successful quality improvement. Published literature from other industries
      emphasizes the importance of a goal-directed change process managed by leaders
      who recognize the need to engage their employees and other leaders in a
      disciplined but flexible way that accommodates external and internal factors and
      uses teams and group learning. It also suggests the importance of organizational
      context and the level of external and internal barriers and facilitators for
      change. The resulting model proposes that priority, change process, and care
      process content are necessary for measurable improvements in quality of care and
      patient outcomes, although internal and external barriers must also be attended
      to and addressed. CONCLUSION: This framework may provide a guide to those in the
      front lines of care who would like to make the care transformations that are
      needed to greatly improve care. It may also be helpful to those who are
      developing or testing interventions and recruiting medical practices for such
      change efforts.

PMID- 17548854
TI  - Disease management: panacea, another false hope, or something in between?
AB  - Disease management is being promulgated by many policy makers, legislators, and a
      burgeoning new disease management industry as the next major hope, together with
      information technology and consumer-directed health care, to bring cost
      containment to runaway costs of health care. Many expect quality improvement as
      well. The concept is being aggressively marketed to employers, health plans, and
      government in the wake of managed care's failure to contain costs. There is
      widespread confusion, however, about what disease management is and what impact
      it will have on patients, physicians, and the health care system itself. In this
      article I give a current snapshot of disease management by briefly addressing (1)
      its rationale and growth, (2) its track record concerning costs and quality of
      care, and (3) its impacts on primary care.

PMID- 17548855
TI  - The impotence of being important--reflections on leadership.
AB  - An observed doctor-patient encounter, in which impotence and importance were
      confused, led me to a reflection on leadership. A sense of importance can be
      destructive in leadership, leading to failure to perform, or impotence.
      Understanding the dangers of self-importance, I am challenged to ensure that I
      regularly reflect on my leadership style.

PMID- 17548858
TI  - Academy builds coalitions for health system reform.

PMID- 17548857
TI  - Academic Family Medicine's response to CTSA.

PMID- 17548856
TI  - Toward an ecosystemic approach to chronic care design and practice in primary
      care.
AB  - Despite the increasing prevalence of chronic conditions and multimorbidities, the
      essential attributes of the structure and delivery of primary care continue to be
      defined in terms of disease-specific approaches and acute conditions. Effective
      improvements will require alternative ways of thinking about chronic care design
      and practice. This essay argues for an ecosystemic understanding of chronic care
      founded on a communal and a dynamic view of the response of the patient, family,
      and health professionals to chronic illness. The communal view highlights the
      cocreative nature of the response to illness and the need to integrate the skills
      and resources of all the participants; what and how the participants learn in the
      course of the illness become central to chronic care. The dynamic view draws
      attention to the unfolding of illness management activities over time and to the
      need to engage the illness at specific time points or recurring time intervals
      that have the potential for important change in the experience of the
      participants. Chronic care would then include design for community, with an
      emphasis on the patient and family as necessary participants in the health care
      team. It would also include design for emergent learning and practice whereby
      health professionals go beyond standardization of care processes to develop new
      ways to harness the participants' imagination and learn from the changing
      experience of illness. Health professionals would also learn to cultivate trust,
      communal engagement, and openness to experimentation that facilitate collective
      learning, and help sharpen the participants' responsiveness to the emergent.

PMID- 17548859
TI  - ABFM's in-training examination.

PMID- 17548860
TI  - P4 = innovation.

PMID- 17548861
TI  - Sexing pinnipeds with ZFX and ZFY loci.
AB  - We developed and tested a protocol for determining the sex of individual
      pinnipeds using the sex-chromosome-specific genes ZFX and ZFY. We screened a
      total of 368 seals (168 crabeater, Lobodon carcinophaga; 159 Weddell,
      Leptonychotes weddellii; and 41 Ross, Ommatophoca rossii) of known or unknown sex
      and compared the molecular sex to the sex assigned at the time of biopsy sample
      collection in the Ross and Amundsen seas, Antarctica. We also screened 6 captive
      northern elephant seals (Mirounga angustirostris) and 2 captive California sea
      lions (Zalophus californianus) of known sex. The assigned sex and genetic sex
      agreed for virtually all seals. Indeed, discrepancies ranged from 0.0% to 6.7%
      among species. It is not clear, however, if the few mis-assignments of sex
      occurred in situ or in the laboratory. The assigned morphological and molecular
      sex might both be correct with the discrepancies owing perhaps to developmental
      effects of environmental pollution. A subset of individuals sequenced at both
      loci revealed no intraspecific sequence variation. There was, however, sequence
      variation among species at both loci, which allowed them to be uniquely
      identified with as few as 2 and as many as 31 nucleotides.

PMID- 17548862
TI  - Localization of white spotting locus in Boxer dogs on CFA20 by genome-wide
      linkage analysis with 1500 SNPs.
AB  - New techniques allow fast genotyping of large numbers of single-nucleotide
      polymorphisms (SNPs) of the genome. These techniques are used to map disorders
      with complex inheritance patterns and require large study groups. Linkage
      analysis of monogenetic traits exploits close family relationships between
      relatively small numbers of cases and controls. Linkage studies are typically
      performed with a set of microsatellite markers spaced at 10 cM. We were
      interested to test whether SNP typing could be applied in genome-wide linkage
      analysis because of the speed of the procedure. White spotting in Boxer dogs was
      chosen as a model because it is a semidominant trait, allowing the assignment of
      locus genotypes to each phenotyped dog. A set of just more than 1500 SNPs were
      typed in 5 families with heterozygous parents and offspring that included 11
      white, 6 brown, and 19 spotted dogs. Multipoint linkage analysis was performed
      and a LOD score of 12.1 was obtained on canine chromosome 20. The CFA20 region
      was the only region with a positive LOD score. The gene MITF, coding for a
      transcription factor implicated in Waardenburg syndrome in humans, is located in
      the region close to a SNP that is in apparent linkage disequilibrium with the
      white spotting locus. Thus, MITF is a likely candidate for involvement in white
      spotting in boxers. We conclude that SNPs, spaced at an average distance of 1.6
      Mb, are highly informative in linkage analysis of monogenic traits and are a
      powerful alternative to microsatellite markers.

PMID- 17548863
TI  - Suitability of cryopreserved isolated lymphocytes for the analysis of micronuclei
      with the cytokinesis-block method.
AB  - In order to assess the applicability of the cytokinesis-block micronucleus assay
      to frozen cells in human biomonitoring and in vitro radiosensitivity studies,
      basal and radiation-induced micronuclei and nucleoplasmic bridges (NPBs) were
      analysed in 28 lymphocyte samples stored frozen from 18 to 123 weeks. All samples
      successfully proliferated and produced a sufficient number of binucleated cells
      to be analysed. The length of the cryopreservation period did not influence cell
      proliferation, nor the incidence of micronuclei and NPBs, both in untreated and
      irradiated cells. Spontaneous levels of micronuclei were modulated by age
      (P=0.007) and by gender (P=0.024), as previously shown for cultures set up using
      fresh cell samples. Irradiation with 2 Gy gamma-rays significantly increased both
      micronuclei and NPBs, which were significantly correlated to each other
      (P=0.004). Radiation-induced micronuclei significantly increased with the age of
      donors (P=0.035), confirming previous findings obtained with fresh cell samples.
      The spontaneous incidences of micronuclei observed in cultures set up with frozen
      lymphocytes were compared with data recorded from the same subjects 5 years
      before using fresh blood samples. A high correlation was observed between the two
      data sets (P=0.004 after removing age and gender effects), highlighting the
      stability during the time of micronuclei as a biomarker of genomic stability, and
      supporting the suitability of frozen cells for cytogenetic analyses in
      biomonitoring and susceptibility studies.

PMID- 17548864
TI  - Genetic polymorphisms of manganese-superoxide dismutase and glutathione-S
      transferase in chronic alcoholic pancreatitis.
AB  - Chronic alcohol consumption is a major risk factor for the development of chronic
      pancreatitis. However, chronic pancreatitis occurs only in a minority of heavy
      drinkers. This variability may be due to yet unidentified genetic factors.
      Several enzymes involved in the degradation of reactive oxidants and xenobiotics,
      such as glutathione-S-transferase P1 (GSTP1) and manganese-superoxide dismutase
      (MnSOD) reveal functional polymorphisms that affect the antioxidative capacity
      and may therefore modulate the development of chronic pancreatitis and long-term
      complications like endocrine and exocrine pancreatic insufficiency. Two
      functional polymorphisms of the MnSOD and the GSTP1 gene were assessed by
      polymerase chain reaction and restriction fragment length polymorphism in 165
      patients with chronic alcoholic pancreatitis, 140 alcoholics without evidence of
      pancreatic disease and 160 healthy control subjects. The distribution of GSTP1
      and MnSOD genotypes were in Hardy-Weinberg equilibrium in the total cohort.
      Genotype and allele frequencies for both genes were not statistically different
      between the three groups. Although genotype MnSOD Ala/Val was seemingly
      associated with the presence of exocrine pancreatic insufficiency, this subgroup
      was too small and the association statistically underpowered. None of the tested
      genotypes affected the development of endocrine pancreatic insufficiency.
      Polymorphisms of MnSOD and GSTP1 are not associated with chronic alcoholic
      pancreatitis. The present data emphasize the need for stringently designed
      candidate gene association studies with well-characterized cases and controls and
      sufficient statistical power to exclude chance observations.

PMID- 17548865
TI  - Prior bleeding enhances the sensitivity of peripheral blood and bone marrow
      micronucleus tests in rats.
AB  - The rat peripheral blood micronucleus (MN) assay is not considered to be a
      sufficient biomarker of genotoxin exposure due to the selective elimination of
      micronucleated cells from peripheral circulation by the spleen. However, several
      recent reports suggest that peripheral blood reticulocytes of rats may represent
      a suitable cell population for use in the MN assay. The MN assay in rats with
      prior bleeding was thus conducted to determine the sensitivity of the bioassay.
      Hirai et al. reported that prior bleeding enhances the sensitivity of the in vivo
      MN test in mice. Based on these findings, the rat was used as a model to see the
      effect of prior bleeding on the sensitivity of the peripheral blood and bone
      marrow MN assays. In the present experiment, young male Sprague-Dawley (SD) rats
      ranging in age from 21 to 24 days were used. However, for the comparison of
      strain-specific induction of MN, Wistar rats were used. The kinetics of MN
      formation were investigated in adult, young bled and non-bled SD rats treated
      with cyclophosphamide (CP). For the MN kinetic study, CP was administered
      intraperitoneally 2 h after bleeding and sampling was done at intervals of 12,
      24, 36, 48 and 96 h after chemical administration. Significant increases in MN
      induction activity in both bone marrow and peripheral blood were observed with
      prior bleeding. To further validate the influence of prior bleeding in the
      induction of MN frequency, two other known genotoxins (chlorambucil and mitomycin
      C) were used. It was concluded that prior bleeding can significantly increase the
      sensitivity of MN induction in both bone marrow and peripheral blood of rats
      compared with non-bled animals. Once validated, this model may be suitable for
      detecting different genotoxins, especially weak and marginally active clastogens.

PMID- 17548866
TI  - Dehydroabietic acid as a biomarker for exposure to colophony.
AB  - BACKGROUND: Colophony (rosin) is a natural product derived from the resin of
      coniferous trees with many industrial applications including soldering fluxes.
      Exposure to colophony fume through soldering is one of the leading causes of
      occupational asthma in the UK. AIMS: To assess occupational exposure to colophony
      from solder fume at selected workplaces in the UK and to investigate the use of
      dehydroabietic acid (DHA) as a biomarker of exposure. METHODS: Six companies in
      the UK electronics industry were visited and occupational hygiene assessments of
      extent and control of exposure to rosin-based solder flux fume were undertaken.
      Urine samples were analysed for one of the main constituents of rosin, DHA.
      RESULTS: There was a positive linear relationship between airborne exposure to
      solder fume and urinary DHA level. The levels of urinary DHA measured in UK
      workers were significantly lower than those previously measured in African
      workers because of the use of appropriate exposure control measures, for example,
      local exhaust ventilation with fixed ducting and flexible hose, tip extraction,
      etc. It is suggested that good occupational hygiene practice would result in
      urinary DHA levels of <3 micromol/mol creatinine in a post-shift urine sample.
      CONCLUSIONS: Urinary DHA is a valid biomarker of exposure to colophony in solder
      fume. Further work on the excretion kinetics of urinary DHA, the possibility of
      skin absorption and further occupational hygiene surveys would be beneficial.

PMID- 17548867
TI  - Reduced health-related quality of life in former North Sea divers is associated
      with decompression sickness.
AB  - BACKGROUND: Diving is associated with long-term effects on several organ systems.
      AIM: The objective was to investigate the impact of decompression sickness (DCS)
      and diving exposure on health-related quality of life (HRQL) in former Norwegian
      North Sea divers. METHODS: HRQL was recorded by a questionnaire in the cohort of
      375 Norwegian North Sea divers registered before 1990. Demographic data, relevant
      health data and data on diving education, history of DCS and SF-36 were recorded
      in 230 divers. RESULTS: All SF-36 sub-scores were significantly reduced compared
      with Norwegian norms. Reduced scores were seen for all scales among divers who
      reported previous DCS compared to those without DCS. A decreasing trend in scores
      was seen when comparing no DCS, skin or joint DCS and neurological DCS. There was
      a decreasing trend in scores related to number of days in saturation and maximal
      depth. Stratification on DCS showed that the impact of saturation diving was
      present only in divers with DCS. CONCLUSIONS: HRQL was reduced in this study
      sample of divers. Having had DCS during the diving career contributed
      significantly to the reduction in all SF-36 scales, and apparently neurological
      DCS has the most pronounced impact. Cumulative diving exposure including days in
      saturation and maximal depth contributed to a reduced HRQL.

PMID- 17548868
TI  - Evaluating causality for occupational cancers: the example of firefighters.
AB  - BACKGROUND: The evaluation of causality in cancers associated with firefighting
      presents problems common to other applications of occupational epidemiology in
      adjudication of individual claims for workers' compensation. A trend in Canada to
      establish legislated presumptions for compensation of firefighters created an
      opportunity to re-evaluate the literature applying medicolegal standards of
      certainty. OBJECTIVE: To evaluate causality in selected cancer categories for
      firefighters using the criteria applied in tort litigation and workers'
      compensation, which is based on the weight of evidence and which is required to
      take into account individual factors. METHODS: The epidemiological literature on
      cancer risk among firefighters was reviewed based on the weight of evidence
      rather than scientific certainty. Generalizable frameworks were formulated to
      define recurrent issues in assessing the evidence from epidemiological studies.
      The evidence for latency and for a threshold effect with duration of employment
      was also examined in order to provide practical guidelines. RESULTS: Presumption
      is justified for the following cancers: bladder, kidney, testicular and brain,
      and lung cancer among non-smokers. Non-Hodgkin lymphoma, leukaemia and myeloma
      (each as a class) not only present particular problems in assessment but also
      merit an assumption of presumption. Four analytical frameworks describe the
      problems in analysis encountered. DISCUSSION: The preponderance of evidence
      supports the presumption of causation for certain cancer, mostly rare. These
      frameworks are applicable to other problems of adjudication that rest on
      interpretation of epidemiological data. The named cancers, taking into account
      the special assessment issues described by each framework, are supported by
      sufficient evidence to conclude that a presumption is warranted but not
      necessarily sufficient evidence to accept as proof by a scientific standard.

PMID- 17548869
TI  - Factors associated with self-assessed work ability.
AB  - BACKGROUND: Symptoms and health problems caused or aggravated by work are common.
      In order to study perceived work ability and associated factors, including those
      related to work, a closer analysis was undertaken in an occupational health
      setting. AIMS: This study aimed to analyse self-assessed work ability and its
      determinants in employees seeking medical advice, with special emphasis on work
      related factors. METHODS: During 723 illness-related visits to occupational
      physicians, questionnaires covering personal data, main health problems, their
      work relatedness, duration and effect on work ability were completed by the
      employee and physician. Factors associated with self-assessed work ability were
      studied in a multinomial logistic regression model. RESULTS: The majority of
      employees considered themselves as being able or partially able to work despite
      the health problem. Independent predictors of impaired work ability were mental
      or musculoskeletal disorders, self-assessed work relatedness of the disease,
      older age, blue-collar work and short duration of the symptoms. If the patient
      was convinced about the benefits of work-related interventions, the risk for
      disability was significantly reduced. CONCLUSIONS: Special attention should be
      paid to the recognition and modification of potential work-related causes of
      disability. In addition, patients with partial work ability should be encouraged
      to stay at work instead of taking sick leave. For effective disability
      management, accommodated work and other evidence-based interventions are needed
      at the workplace.

PMID- 17548870
TI  - Putting the horse back in front of the cart: using visions and decisions about
      high-quality learning experiences to drive course design.

PMID- 17548871
TI  - Potent cells.

PMID- 17548872
TI  - WormClassroom.org: an inquiry-rich educational web portal for research resources
      of Caenorhabditis elegans.
AB  - The utilization of biology research resources, coupled with a "learning by
      inquiry" approach, has great potential to aid students in gaining an
      understanding of fundamental biological principles. To help realize this
      potential, we have developed a Web portal for undergraduate biology education,
      WormClassroom.org, based on current research resources of a model research
      organism, Caenorhabditis elegans. This portal is intended to serve as a resource
      gateway for students to learn biological concepts using C. elegans research
      material. The driving forces behind the WormClassroom website were the strengths
      of C. elegans as a teaching organism, getting researchers and educators to work
      together to develop instructional materials, and the 3 P's (problem posing,
      problem solving, and peer persuasion) approach for inquiry learning. Iterative
      assessment is an important aspect of the WormClassroom site development because
      it not only ensures that content is up-to-date and accurate, but also verifies
      that it does, in fact, aid student learning. A primary assessment was performed
      to refine the WormClassroom website utilizing undergraduate biology students and
      nonstudent experts such as C. elegans researchers; results and comments were used
      for site improvement. We are actively encouraging continued resource
      contributions from the C. elegans research and education community for the
      further development of WormClassroom.

PMID- 17548873
TI  - Genome Consortium for Active Teaching: meeting the goals of BIO2010.
AB  - The Genome Consortium for Active Teaching (GCAT) facilitates the use of modern
      genomics methods in undergraduate education. Initially focused on microarray
      technology, but with an eye toward diversification, GCAT is a community working
      to improve the education of tomorrow's life science professionals. GCAT
      participants have access to affordable microarrays, microarray scanners, free
      software for data analysis, and faculty workshops. Microarrays provided by GCAT
      have been used by 141 faculty on 134 campuses, including 21 faculty that serve
      large numbers of underrepresented minority students. An estimated 9480
      undergraduates a year will have access to microarrays by 2009 as a direct result
      of GCAT faculty workshops. Gains for students include significantly improved
      comprehension of topics in functional genomics and increased interest in
      research. Faculty reported improved access to new technology and gains in
      understanding thanks to their involvement with GCAT. GCAT's network of supportive
      colleagues encourages faculty to explore genomics through student research and to
      learn a new and complex method with their undergraduates. GCAT is meeting
      important goals of BIO2010 by making research methods accessible to
      undergraduates, training faculty in genomics and bioinformatics, integrating
      mathematics into the biology curriculum, and increasing participation by
      underrepresented minority students.

PMID- 17548874
TI  - Collaborative co-mentored dissertations spanning institutions: influences on
      student development.
AB  - The Graduate Partnerships Program (GPP), established in 2000, links universities
      with National Institutes of Health (NIH) laboratories for predoctoral training.
      Several partnerships required that students create collaborative dissertations
      between at least one NIH and one university research mentor. More than 60
      students have entered into these co-mentored research collaborations, and many
      others established them even though not required. Much was learned about the
      experiences of these and other GPP students by using structured interviews as
      part of a formal self-study of the GPP in 2005. Complications of trying to work
      with two mentors are managed through careful program design and mentor selection.
      In the collaborative model, students develop a complex set of scientific and
      interpersonal skills. They lead their own independent research projects, drawing
      on the expertise of multiple mentors and acquiring skills at negotiating
      everyone's interests. They develop high levels of independence, maturity,
      flexibility, and the ability to see research questions from different
      perspectives. No evidence was found that co-mentoring diminishes the normally
      expected accomplishments of a student during the Ph.D. Multi-mentored
      dissertations require skills not all graduate students may possess this early in
      training, but for those who do, they can promote rapid and extensive development
      of skills needed for collaborative, interdisciplinary research.

PMID- 17548875
TI  - Prescribed active learning increases performance in introductory biology.
AB  - We tested five course designs that varied in the structure of daily and weekly
      active-learning exercises in an attempt to lower the traditionally high failure
      rate in a gateway course for biology majors. Students were given daily multiple
      choice questions and answered with electronic response devices (clickers) or
      cards. Card responses were ungraded; clicker responses were graded for
      right/wrong answers or participation. Weekly practice exams were done as an
      individual or as part of a study group. Compared with previous versions of the
      same course taught by the same instructor, students in the new course designs
      performed better: There were significantly lower failure rates, higher total exam
      points, and higher scores on an identical midterm. Attendance was higher in the
      clicker versus cards section; attendance and course grade were positively
      correlated. Students did better on clicker questions if they were graded for
      right/wrong answers versus participation, although this improvement did not
      translate into increased scores on exams. In this course, achievement increases
      when students get regular practice via prescribed (graded) active-learning
      exercises.

PMID- 17548876
TI  - Learning to improve: using writing to increase critical thinking performance in
      general education biology.
AB  - Increasingly, national stakeholders express concern that U.S. college graduates
      cannot adequately solve problems and think critically. As a set of cognitive
      abilities, critical thinking skills provide students with tangible academic,
      personal, and professional benefits that may ultimately address these concerns.
      As an instructional method, writing has long been perceived as a way to improve
      critical thinking. In the current study, the researchers compared critical
      thinking performance of students who experienced a laboratory writing treatment
      with those who experienced traditional quiz-based laboratory in a general
      education biology course. The effects of writing were determined within the
      context of multiple covariables. Results indicated that the writing group
      significantly improved critical thinking skills whereas the non-writing group did
      not. Specifically, analysis and inference skills increased significantly in the
      writing group but not the non-writing group. Writing students also showed greater
      gains in evaluation skills; however, these were not significant. In addition to
      writing, prior critical thinking skill and instructor significantly affected
      critical thinking performance, whereas other covariables such as gender,
      ethnicity, and age were not significant. With improved critical thinking skill,
      general education biology students will be better prepared to solve problems as
      engaged and productive citizens.

PMID- 17548877
TI  - A faculty team works to create content linkages among various courses to increase
      meaningful learning of targeted concepts of microbiology.
AB  - As research faculty with expertise in the area of host-pathogen interactions
      (HPI), we used a research group model to effect our professional development as
      scientific educators. We have established a working hypothesis: The
      implementation of a curriculum that forms bridges between our seven HPI courses
      allows our students to achieve deep and meaningful learning of HPI concepts.
      Working collaboratively, we identified common learning goals, and we chose two
      microorganisms to serve as anchors for student learning. We instituted variations
      of published active-learning methods to engage students in research-oriented
      learning. In parallel, we are developing an assessment tool. The value of this
      work is in the development of a teaching model that successfully allowed faculty
      who already work collaboratively in the research area of HPI to apply a "research
      group approach" to further scientific teaching initiatives at a research
      university. We achieved results that could not be accomplished by even the most
      dedicated instructor working in isolation.

PMID- 17548878
TI  - Cooperative learning in industrial-sized biology classes.
AB  - This study examined the impact of cooperative learning activities on student
      achievement and attitudes in large-enrollment (>250) introductory biology
      classes. We found that students taught using a cooperative learning approach
      showed greater improvement in their knowledge of course material compared with
      students taught using a traditional lecture format. In addition, students viewed
      cooperative learning activities highly favorably. These findings suggest that
      encouraging students to work in small groups and improving feedback between the
      instructor and the students can help to improve student outcomes even in very
      large classes. These results should be viewed cautiously, however, until this
      experiment can be replicated with additional faculty. Strategies for potentially
      improving the impact of cooperative learning on student achievement in large
      courses are discussed.

PMID- 17548879
TI  - Biology Intensive Orientation for Students (BIOS): a biology "boot camp".
AB  - The Biology Intensive Orientation for Students (BIOS) Program was designed to
      assess the impact of a 5-d intensive prefreshman program on success and retention
      of biological science majors at Louisiana State University. The 2005 pilot
      program combined content lectures and examinations for BIOL 1201, Introductory
      Biology for Science Majors, as well as learning styles assessments and
      informational sessions to provide the students with a preview of the requirements
      of biology and the pace of college. Students were tracked after their BIOS
      participation, and their progress was compared with a control group composed of
      students on the BIOS waiting list and a group of BIOL 1201 students who were
      identified as the academic matches to the BIOS participants (high school GPA, ACT
      score, and gender). The BIOS participants performed significantly better on the
      first and second exams, they had a higher course average, and they had a higher
      final grade than the control group. These students also had higher success rates
      (grade of "A," "B," or "C") during both the fall and spring semesters and
      remained on track through the first semester of their sophomore year to graduate
      in 4 yr at a significantly higher rate than the control group.

PMID- 17548880
TI  - Teaching human genetics with mustard: rapid cycling Brassica rapa (fast plants
      type) as a model for human genetics in the classroom laboratory.
AB  - We have developed experiments and materials to model human genetics using rapid
      cycling Brassica rapa, also known as Fast Plants. Because of their self
      incompatibility for pollination and the genetic diversity within strains, B. rapa
      can serve as a relevant model for human genetics in teaching laboratory
      experiments. The experiment presented here is a paternity exclusion project in
      which a child is born with a known mother but two possible alleged fathers.
      Students use DNA markers (microsatellites) to perform paternity exclusion on
      these subjects. Realistic DNA marker analysis can be challenging to implement
      within the limitations of an instructional lab, but we have optimized the
      experimental methods to work in a teaching lab environment and to maximize the
      "hands-on" experience for the students. The genetic individuality of each B. rapa
      plant, revealed by analysis of polymorphic microsatellite markers, means that
      each time students perform this project, they obtain unique results that foster
      independent thinking in the process of data interpretation.

PMID- 17548881
TI  - Minimally invasive lumbar spinal fusion.
AB  - Minimally invasive techniques for lumbar spine fusion have been developed in an
      attempt to decrease the complications related to traditional open exposures (eg,
      infection, wound healing problems). Anterior minimally invasive procedures
      include laparoscopic and mini-open anterior lumbar interbody fusion as well as
      the lateral transpsoas and percutaneous presacral approaches. Posterior
      techniques typically use a tubular retractor system that avoids the muscle
      stripping associated with open procedures. These techniques can be applied to
      both posterior and transforaminal lumbar interbody fusion procedures. Many
      initial reports have shown similar clinical results in terms of spinal fusion
      rates for both traditional open and minimally invasive posterior approaches.
      However, the anterior minimally invasive procedures are often associated with
      significantly greater incidence of complications and technical difficulty than
      their associated open approaches. There is a steep learning curve associated with
      minimally invasive techniques, and surgeons should not expect to master them in
      the first several cases.

PMID- 17548882
TI  - Ankle syndesmotic injury.
AB  - Ankle syndesmotic injury does not necessarily lead to ankle instability; however,
      the coexistence of deltoid ligament injury critically destabilizes the ankle
      joint. Syndesmotic injury may occur in isolation or may be associated with ankle
      fracture. In the absence of fracture, physical examination findings suggestive of
      injury include ankle tenderness over the anterior aspect of the syndesmosis and a
      positive squeeze or external rotation test. Radiographic findings usually include
      increased tibiofibular clear space decreased tibiofibular overlap, and increased
      medial clear space. However, syndesmotic injury may not be apparent
      radiographically; thus, routine stress testing is necessary for detecting
      syndesmotic instability. The goals of management are to restore and maintain the
      normal tibiofibular relationship to allow for healing of the ligamentous
      structures of the syndesmosis. Fixation of the syndesmosis is indicated when
      evidence of a diastasis is present. This may be detected preoperatively, in the
      absence of fracture, or intraoperatively, after rigid fixation of the medial
      malleolus and fibula fractures. Failure to diagnose and stabilize syndesmotic
      disruption adversely affects outcome.

PMID- 17548883
TI  - Rotator cuff tear arthropathy.
AB  - Rotator cuff tear arthropathy represents a spectrum of shoulder pathology
      characterized by rotator cuff insufficiency, diminished acromiohumeral distance
      with impingement syndromes, and arthritic changes of the glenohumeral joint.
      Additional features may include subdeltoid effusion, humeral head erosion, and
      acetabularization of the acromion. Although the progression of rotator cuff tears
      seems to play a role in the development of cuff tear arthropathy, information is
      lacking regarding the natural progression of rotator cuff tears to cuff tear
      arthropathy. Controversy remains about the role of basic calcium phosphate
      crystals in the development of cuff tear arthropathy. Nonsurgical management is
      the first line of treatment in most patients. Traditionally, surgical management
      of rotator cuff tear arthropathy has been disappointing because of the
      development of complications long-term and poor patient satisfaction with
      functional outcomes. Recent studies, however, report promising experience with
      reverse ball-and-socket arthroplasty.

PMID- 17548884
TI  - Acute proximal hamstring rupture.
AB  - Hamstring strain is common in athletes, and both diagnosis and surgical treatment
      of this injury are becoming more common. Nonsurgical treatment of complete
      ruptures has resulted in complications such as muscle weakness and sciatic
      neuralgia. Surgical treatment recently has been advocated to repair the complete
      rupture of the hamstring tendons from the ischial tuberosity. Surgical repair
      involves a transverse incision in the gluteal crease, protection of the sciatic
      nerve, mobilization of the ruptured tendons, and repair to the ischial tuberosity
      with the use of suture anchors. Reports in the literature of surgical treatment
      of proximal hamstring rupture are few, and most series have had a relatively
      small number of patients. Surgical repair results project 58% to 85% rate of
      return to function and sports activity, near normal strength, and decreased pain.

PMID- 17548885
TI  - Lower extremity injuries in the skeletally immature athlete.
AB  - The heightened intensity of training and competition among young athletes places
      them at increased risk for both acute and chronic injuries. Prompt recognition
      and treatment of such injuries are critical to prevent long-term functional
      disability and deformity. These injuries occur in patterns unique to the
      skeletally immature athlete, given their developing epiphyses and ossification
      centers and supporting ligamentous structures. Children and adolescents who
      participate in recreational and organized sports are particularly susceptible to
      a broad spectrum of lower extremity injuries involving both the osseous and soft
      tissue structures. Fundamental knowledge of the pathophysiology of injury helps
      the clinician in determining management. Early recognition of acute traumatic
      injuries, along with preventive regimens and knowledge of both nonsurgical and
      surgical treatment protocols, has helped to restore and maintain normal lower
      extremity function in the skeletally immature athlete.

PMID- 17548886
TI  - Open hindfoot injuries.
AB  - Successful management of open talar and calcaneal injuries of the hindfoot is a
      formidable orthopaedic challenge. The soft-tissue disruption associated with
      these high-energy traumatic injuries adds to treatment complexity. Extensive
      fracture comminution and cartilage damage are often present with calcaneal
      fracture. Osteonecrosis is commonly associated with talar injury. Treatment may
      be divided into acute and reconstructive phases. Successful outcome is dependent
      on several variables--accurate fracture reduction, timing of intervention,
      prevention of infection, and meticulous soft-tissue handling. Anatomic fracture
      or joint reconstruction may not be possible. Joint stiffness and posttraumatic
      arthritis are common and may be debilitating. Complications, such as infection
      and osteonecrosis, also can be devastating. Long-term outcomes are frequently
      unsatisfactory. Chronic ambulatory dysfunction and persistent neurogenic pain may
      result despite appropriate management. With severe complex open fractures and
      extended soft-tissue injury, limb amputation may be the best treatment option.

PMID- 17548887
TI  - Mechanism for FGF-1 to regulate biogenesis of apoE-HDL in astrocytes.
AB  - Fibroblast growth factor-1 (FGF-1) is secreted by astrocytes and stimulates
      apolipoprotein E (apoE)-HDL biogenesis by an autocrine mechanism to help in
      recovery from brain injury. In apoE-deficient mouse astrocytes, FGF-1 stimulated
      cholesterol biosynthesis without enhancing its release, indicating a signaling
      pathway independent of apoE biosynthesis upregulation. SU5402, an inhibitor of
      FGF receptor, inhibited FGF-1-induced phosphorylation of MEK, ERK, and Akt, as
      well as all the apoE-HDL biogenesis-related events in rat astrocytes. LY294002,
      an inhibitor of phosphatidylinositide 3-OH kinase (PI3K) and of Akt
      phosphorylation, inhibited apoE-HDL secretion but not cholesterol biosynthesis,
      whereas U0126, an inhibitor of MEK and of ERK phosphorylation, inhibited
      cholesterol biosynthesis but not apoE-HDL secretion. Increase of apoE-mRNA by FGF
      1 was not influenced by either inhibitor. When rat apoE/pcDNA3.his was
      transfected to transformed rat astrocyte GA-1 cells that otherwise do not
      synthesize apoE (GA-1/25), FGF-1 did not influence apoE-mRNA, but did increase
      the apoE secretion and Akt phosphorylation that were suppressed by LY294002.
      Lipid biosynthesis was increased by FGF-1 in GA-1/25 cells and suppressed by
      U0126. FGF-1 upregulates apoE-HDL biogenesis by three independent signaling
      pathways. The PI3K/Akt pathway upregulates secretion of apoE/apoE-HDL, the
      MEK/ERK pathway stimulates cholesterol biosynthesis, and an unknown pathway
      enhances apoE transcription.

PMID- 17548888
TI  - Development of a novel method to determine very low density lipoprotein kinetics.
AB  - Isotopic tracer methods of determining triglyceride-rich lipoprotein (TRL)
      kinetics are costly, time-consuming, and labor-intensive. This study aimed to
      develop a simpler and cost-effective method of obtaining TRL kinetic data, based
      on the fact that chylomicrons compete with large VLDL (VLDL(1); S(f) = 60-400)
      for the same catalytic pathway. Ten healthy subjects [seven men; fasting
      triglyceride (TG), 44.3-407.6 mg/dl; body mass index, 21-35 kg/m(2)] were given
      an intravenous infusion of a chylomicron-like TG emulsion (Intralipid; 0.1 g/kg
      bolus followed by 0.1 g/kg/h infusion) for 75-120 min to prevent the clearance of
      VLDL(1) by lipoprotein lipase. Multiple blood samples were taken during and after
      infusion for separation of Intralipid, VLDL(1), and VLDL(2) by
      ultracentrifugation. VLDL(1)-apolipoprotein B (apoB) and TG production rates were
      calculated from their linear increases in the VLDL(1) fraction during the
      infusion. Intralipid-TG clearance rate was determined from its exponential decay
      after infusion. The production rates of VLDL(1)-apoB and VLDL(1)-TG were (mean +/
      SEM) 25.4 +/- 3.9 and 1,076.7 +/- 224.7 mg/h, respectively, and the Intralipid
      TG clearance rate was 66.9 +/- 11.7 pools/day. Kinetic data obtained from this
      method agree with values obtained from stable isotope methods and show the
      expected relationships with indices of body fatness and insulin resistance (all P
      < 0.05). The protocol is relatively quick, inexpensive, and transferable to
      nonspecialist laboratories.

PMID- 17548889
TI  - Genetic toxicity assessment: employing the best science for human safety
      evaluation Part VII: Why not start with a single test: a transformational
      alternative to genotoxicity hazard and risk assessment.
AB  - A transformational alternative for genotoxicity hazard and risk assessment is
      proposed to the current standard regulatory test battery. In principle, the
      proposed approach consists of a single in vitro test system with high genomic
      sequence homology to humans that addresses the relevant principal genetic lesions
      assessed in the current test battery. The single test system also possesses
      higher throughput attributes to permit the screening of large numbers of
      compounds and allow for an initial differentiation of genotoxic mechanisms (i.e.,
      direct vs. indirect mechanisms) by how the hazard end point is measured. To
      differentiate compounds showing positive results, toxicogenomic analysis can be
      conducted to evaluate genotoxic mechanisms and further support risk assessment.
      Lastly, the results from the single test system can be followed up with a
      complementary in vivo assessment to establish mechanistic relevance at potential
      target tissues. Here, we propose the in vitro (yeast) DNA deletion (DEL)
      recombination assay as a single test alternative to the current genotoxicity test
      battery with a mechanistic follow up toxicogenomic analysis of genotoxic stress
      response as one approach that requires broader evaluation and validation. In this
      assay, intrachromosomal recombination events between a repeated DNA sequence lead
      to DNA deletions, which have been shown to be inducible by a variety of
      carcinogens including those both negative and positive in the standard Salmonella
      Ames assay. It is hoped that the general framework outlined along with this
      specific example will provoke broader interest to propose other potential test
      systems.

PMID- 17548890
TI  - A dosimetric analysis of the acute behavioral effects of inhaled toluene in rats.
AB  - Knowledge of the appropriate metric of dose for a toxic chemical facilitates
      quantitative extrapolation of toxicity observed in the laboratory to the risk of
      adverse effects in the human population. Here, we utilize a physiologically based
      toxicokinetic (PBTK) model for toluene, a common volatile organic compound (VOC),
      to illustrate that its acute behavioral effects in rats can be quantitatively
      predicted on the basis of its concentration in the brain. Rats previously trained
      to perform a visual signal detection task for food reward performed the task
      while inhaling toluene (0, 1200, 1600, 2000, and 2400 ppm in different test
      sessions). Accuracy and speed of responding were both decreased by toluene; the
      magnitude of these effects increased with increasing concentration of the vapor
      and with increasing duration of exposure. Converting the exposure conditions to
      brain toluene concentration using the PBTK model yielded a family of overlapping
      curves for each end point, illustrating that the effects of toluene can be
      described quantitatively by its internal dose at the time of behavioral
      assessment. No other dose metric, including inhaled toluene concentration,
      duration of exposure, the area under the curve of either exposure (ppm h), or
      modeled brain toluene concentration (mg-h/kg), provided unambiguous predictions
      of effect. Thus, the acute behavioral effects of toluene (and of other VOCs with
      a similar mode of action) can be predicted for complex exposure scenarios by
      simulations that estimate the concentration of the VOC in the brain from the
      exposure scenario.

PMID- 17548891
TI  - Temporal integration in nasal lateralization of homologous alcohols.
AB  - Through temporal integration, sensory systems accumulate stimulus energy, e.g.,
      photons, acoustic energy, or molecules, over time to detect weaker signals than
      they otherwise could. Past studies found imperfect temporal integration in
      detection of nasal irritation: To maintain a fixed level of detection, one must
      increase stimulus duration by more than twofold to compensate for cutting
      concentration in half. Despite this generality, integration varied widely among
      compounds, from nearly perfect, i.e., an increase in duration of slightly more
      than twofold could compensate for cutting concentration in half, to highly
      imperfect. How do such differences relate to molecular parameters? Perhaps
      molecules that more readily dissolve into the lipid-rich perireceptor environment
      will accumulate, and therefore integrate, better over time. To test this
      hypothesis, studies compared temporal integration for three compounds that differ
      systematically in lipid solubility: n-ethanol, n-butanol, and n-hexanol. Subjects
      were healthy, adult humans. Nasal lateralization was used to measure irritation
      threshold. Subjects received a fixed concentration of a single compound within
      each experimental session, and stimulus duration was varied to find the briefest
      stimulus subjects could reliably lateralize. Concentration and compound varied
      across sessions. Consistent with the hypothesis, integration did become closer to
      perfect as lipid solubility increased. That just one molecular parameter can help
      predict degree of integration suggests that a structure-activity approach to
      understanding temporal integration shows promise.

PMID- 17548892
TI  - Postpartum functioning in mothers with multiple sclerosis.
AB  - Increased family demands during the postpartum period together with having to
      cope with symptoms and curtailed everyday functioning associated with multiple
      sclerosis (MS) suggest the need for additional support for mothers with MS
      throughout the first postpartum year. This study investigated factors (MS
      duration, MS relapse, symptoms, social support) that affect functional
      performance of 172 mothers with MS during the second 6-month postpartum period.
      Data were analyzed with descriptive statistics and path analysis. Findings
      indicated a good fit of the path models to the data at 9 and 12 months.
      Significant effects at both 9 and 12 months included positive relationships
      between duration of MS and symptoms and between social support and functional
      performance. Significant negative relationships were observed between symptoms
      and both social support and functional performance. Social support mediated the
      relationship between symptoms and functional performance. Findings suggest the
      importance of continued social support throughout the first postpartum year.

PMID- 17548893
TI  - Symptom assessment of patients with chronic obstructive pulmonary disease.
AB  - The primary purpose of this secondary data analysis was to evaluate the efficacy
      and suitability of the Memorial Symptom Assessment Scale (MSAS) for use with
      patients with severe chronic obstructive pulmonary disease (COPD). Symptoms
      experienced by patients with severe COPD were assessed in the original
      investigation using the 32-item MSAS. The sample consisted of 72 individuals with
      COPD ranging in age from 36 to 79 years. To increase its efficiency for use with
      severely ill COPD patients, the original MSAS was shortened to include the 19
      most frequently reported symptoms. Reliability of the revised tool remained high
      (Cronbach's alpha = .86). Content and convergent validity of the revised tool
      were also established. The revised MSAS appears to be an appropriate measure of
      the multidimensional, multisymptom experience of patients with severe COPD.

PMID- 17548894
TI  - Pain management decision making among long-term care physicians and nurses.
AB  - The purpose of this study is to explore attitudes and beliefs that affect
      decisions about prescribing and administering pain medications in older adults
      who live in long-term care (LTC), with a particular emphasis on those with
      cognitive impairment. At each of the four participating LTC facilities, data were
      gathered from three separate groups of health care professionals: physicians,
      registered nurses, and registered practical nurses. Based on grounded theory, a
      model was developed that highlighted critical decision points for nurses and
      physicians regarding pain management. The major themes that emerged from the data
      concerned pain assessment (lack of recognition of pain, uncertainty about the
      accuracy of pain assessment and diagnosis) and treatment (reluctance to use
      opioids, working to individualize pain treatments, issues relating to physician
      trust of the nurse on prescribing patterns). These findings may facilitate the
      development of innovative approaches to pain management in LTC settings.

PMID- 17548896
TI  - The mechanisms of action for treatments of type 2 diabetes.

PMID- 17548897
TI  - Emerging treatments for patients with type 2 diabetes.

PMID- 17548898
TI  - Educating patients with type 2 diabetes on a new class of drug, dipeptidyl
      peptidase 4 inhibitors.

PMID- 17548899
TI  - Case presentation: a patient with type 2 diabetes.

PMID- 17548900
TI  - Induction of death receptor 5 and suppression of survivin contribute to
      sensitization of TRAIL-induced cytotoxicity by quercetin in non-small cell lung
      cancer cells.
AB  - The natural flavonoid quercetin has been suggested by epidemiological studies to
      have preventive activity against lung cancer; however, the mechanism of which has
      not been well elucidated. In this report, we demonstrate that quercetin
      significantly enhances tumor necrosis factor-related apoptosis-inducing ligand
      (TRAIL)-induced cytotoxicity in non-small cell lung cancer (NSCLC) cells.
      Quercetin increased expression of death receptor (DR) 5, whereas it had no effect
      on that of other components of the death-inducing signaling complex. Conversely,
      the expression of survivin was potently inhibited by quercetin. We further
      determined that Protein Kinase C (PKC) is essential for DR5 induction but is
      dispensable for suppression of survivin expression. In contrast, the blockage of
      the serine/threonine kinase Akt activity by quercetin is important for inhibition
      of survivin expression but not induction of DR5. These results suggest the
      pathways for regulation of DR5 and survivin expression by quercetin are distinct.
      Importantly, suppression of survivin-sensitized TRAIL-induced cell death and
      blockage of DR5 expression suppressed the synergistic cytotoxicity induced by
      quercetin and TRAIL co-treatment. On the whole, our data show that quercetin
      sensitizes TRAIL-induced cytotoxicity in lung cancer cells through two
      independent pathways: induction of DR5 and suppression of survivin expression,
      which may underlie the mechanism of the lung cancer preventive activity of
      quercetin. The potentiation of TRAIL-induced NSCLC cell death could be implicated
      in lung cancer therapy and prevention.

PMID- 17548901
TI  - Acetyl derivative of quercetin 3-methyl ether-induced cell death in human
      leukemia cells is amplified by the inhibition of ERK.
AB  - Flavonoids are polyphenolic compounds that are ubiquitously in plants and display
      a vast array of biological activities. Here we have studied the effect of the
      phenylbenzo-gamma-pyrone-derivative quercetin 3-methyl ether tetracetate (QD),
      obtained by acetylation of the natural product quercetin 3-methyl ether, on cell
      viability of human leukemia HL-60 and U937 cell lines. The results show that QD
      was cytotoxic and induced G2-M phase cell cycle arrest on both cell lines and it
      was a potent apoptotic inducer on HL-60 cells. QD-induced apoptosis is (i)
      mediated by caspase activation, since it was prevented by the non-specific
      caspase inhibitor z-VAD-fmk, (ii) associated with cytochrome c release and (iii)
      triggered in Bcl-2 over-expressing U937 cells. The treatment of HL-60 and U937
      cells with QD also induces the activation of the mitogen-activated protein
      kinases (MAPKs) pathway, including c-Jun N-terminal kinase, p38 mitogen-activated
      protein kinase and extracellular signal-regulated kinases (ERK) 1/2. Inhibition
      of c-Jun N-terminal kinase by SP600125 and of p38 mitogen-activated protein
      kinase by SB203580 had no influence on QD-mediated apoptosis. In contrast,
      inhibition of ERK1/2 with the pharmacologic inhibitors U0126 or PD98059, together
      with QD, resulted in an important enhancement of apoptosis. Cells are sensitized
      to QD-mediated apoptosis after blocking ERK1/2, which suggests that inhibition of
      this pathway is a valuable strategy to increase the sensitivity of human leukemia
      HL-60 cells toward QD.

PMID- 17548902
TI  - A bibliometric analysis of scientific production in cancer molecular
      epidemiology.
AB  - OBJECTIVES: The main purpose of this research was to compare the scientific
      production in the field of cancer molecular epidemiology among countries and to
      evaluate the publication trend between 1995 and 2004. METHODS: A bibliometric
      study was carried out searching the PubMed database with a combined search
      strategy based on the keywords listed in the medical subject headings and a free
      text search. Only articles from a representative subset of 92 journals-
      accounting for 80% of papers identified--were selected for the analysis, and the
      resulting 13,240 abstracts were manually checked according to a list of basic
      inclusion criteria. The study evaluated the number of publications and the impact
      factor (mean and sum), absolute and normalized by country population and gross
      domestic product. RESULTS: A total of 3,842 citations were finally selected for
      the analysis. Thirty-seven percent came from the European Union (UK, Germany,
      Italy, France and Sweden ranking at the top), 31.6% from USA and 9.7% from Japan.
      The highest mean impact factor was reported for Canada (6.3), USA (5.9), Finland
      (5.8) and UK (5.2). Finland, Sweden and Israel had the best ratio between
      scientific production and available resources. 'Genetic polymorphism, glutathione
      transferase, breast neoplasm, risk factors, case-control studies and polymerase
      chain reaction' were the most used keywords in each of the subgroups evaluated,
      although inclusion criteria may have privileged studies dealing with exogenous
      carcinogens. CONCLUSION: Cancer molecular epidemiology is an expanding area
      attracting an increasing interest. The identification of an operative definition
      is a necessary condition to give to this discipline a unique scientific identity.

PMID- 17548903
TI  - MAP17 enhances the malignant behavior of tumor cells through ROS increase.
AB  - Tumorigenesis occurs when the mechanisms involved in the control of tissue
      homeostasis are disrupted and cells stop responding to physiological signals.
      Therefore, genes capable of desensitizing tumoral cells from physiological
      signals may provide a selective advantage within the tumoral mass and influence
      the outcome of the disease. We undertook a large-scale genetic screen to identify
      genes able to alter the cellular response to physiological signals and provide
      selective advantage once tumorigenesis has begun. We identified MAP17, a small 17
      kDa non-glycosylated membrane protein previously identified by differential
      display being over-expressed in carcinomas. Tumor cells that over-express MAP17
      show an increased tumoral phenotype with enhanced proliferative capabilities both
      in presence or absence of contact inhibition, decreased apoptotic sensitivity and
      increased migration. MAP17-expressing clones also grow better in nude mice. The
      increased malignant cell behavior induced by MAP17 are associated with an
      increase in reactive oxygen species (ROS) production, and the treatment of MAP17
      expressing cells with antioxidants results in a reduction in the tumorigenic
      properties of these cells. Treatment of melanoma cells with inhibitors of Na+
      coupled co-transporters lead to an inhibition of ROS increase and a decrease in
      the malignant cell behavior in MAP17-expressing clones. Finally, we show that
      MAP17-dependent ROS increase and tumorigenesis are dependent on its PDZ-binding
      domain, since disruption of its sequence by point mutations abolishes its ability
      to enhance ROS production and tumorigenesis. Our work shows the tumorigenic
      capability of MAP17 through a connection between Na+-coupled co-transporters and
      ROS.

PMID- 17548904
TI  - Changing pattern of hysterectomies for benign conditions.

PMID- 17548905
TI  - Complicated parapneumonic effusion and empyema thoracis: microbiology and
      predictors of adverse outcomes.
AB  - OBJECTIVES: To describe the microbiological characteristics of a cohort of
      patients with complicated parapneumonic effusion and empyema thoracis, and to
      identify the potential risk factors for adverse outcomes, with particular
      reference to the choice of empirical antibiotics, intrapleural fibrinolytics,
      adherence to management guidelines, and input from pulmonologists. DESIGN:
      Retrospective review. SETTING: Regional hospital, Hong Kong. PATIENTS: All
      patients with a diagnosis of complicated parapneumonic effusion/empyema thoracis
      admitted between January 2003 and June 2005. MAIN OUTCOME MEASURES:
      Microbiological characteristics, mortality, and surgery-free survival. RESULTS.
      There were 63 patients, with a mean age of 64 (standard deviation, 16) years and
      a male-to-female ratio of 45:18. The pleural fluid culture positivity rate was
      68%; Streptococcus milleri (19%), Bacteroides (14%), Klebsiella pneumoniae (12%),
      and Peptostreptococcus (7%) were the most common organisms. Thirteen (21%)
      patients died during their index admission. Use of intrapleural fibrinolytics
      according to the guideline was associated with survival (P=0.001) while
      discordant initial antibiotic use was associated with mortality (P=0.002).
      Discordant initial antibiotic use was also independently associated with reduced
      surgery-free survival (P<0.001). Subgroup analysis showed that early intrapleural
      fibrinolytic use (within 4 days of diagnosis) was associated with decreased
      mortality (P<0.001), increased surgery-free survival (P=0.005), and shorter
      hospital stay (P=0.039). CONCLUSION: Organisms identified from complicated
      parapneumonic effusion and empyema thoracis differ from those giving rise to
      community-acquired pneumonia. In these patients, adherence to guidelines, early
      concordant antibiotic treatment, intrapleural fibrinolytics, and input from a
      pulmonologist were associated with improved outcomes.

PMID- 17548906
TI  - An audit on hysterectomy for benign diseases in public hospitals in Hong Kong.
AB  - OBJECTIVE: To assess the standard of hysterectomy in public hospitals in Hong
      Kong, so as to improve the quality of patient care and outcome. DESIGN: Clinical
      audit. SETTING: Twelve Hong Kong Hospital Authority public hospitals. PATIENTS:
      All patients undergoing hysterectomy for benign gynaecological conditions during
      the period from 1 July 2002 to 31 December 2002 inclusive. RESULTS: A total of
      1330 patients were included for analysis: 934 (70.2%) having abdominal
      hysterectomies, 184 (13.8%) having laparoscopic hysterectomies, and 212 (15.9%)
      undergoing vaginal hysterectomies. Uterine fibroids constituted the commonest
      indication for abdominal (73.7%) and laparoscopic (61.4%) hysterectomies, while
      genital prolapse was the most common indication (96.2%) for vaginal hysterectomy.
      The majority of patients undergoing laparoscopic and vaginal hysterectomy (86.3%
      and 84.8% respectively) were given prophylactic antibiotics, in contrast to only
      45.8% of those undergoing abdominal hysterectomy. In all, 85.8% of the abdominal
      and vaginal hysterectomies performed by trainees were supervised, while for
      trainees performing laparoscopic hysterectomy, all had specialists as their first
      assistant. The overall incidence of complications for vaginal hysterectomy was
      lower than that for both abdominal hysterectomy (P<0.001) and laparoscopic
      hysterectomy (P<0.05). Infectious morbidity was significantly higher in patients
      undergoing abdominal hysterectomy without prophylactic antibiotics. CONCLUSION:
      The overall incidence of complications was lower for vaginal hysterectomies, as
      compared to both abdominal and laparoscopic hysterectomies, whereas the risk of
      urinary tract injury was significantly higher for laparoscopic hysterectomy.
      According to our audit, the level of supervision for the trainees was high.
      However, routine antibiotic prophylaxis should be more consistently used in the
      territory.

PMID- 17548907
TI  - Clinicopathological correlates in a cohort of Hong Kong breast cancer patients
      presenting with screen-detected or symptomatic disease.
AB  - OBJECTIVES: To examine the differences in breast cancer presentation by analysing
      our recent experience in the diagnosis and management of breast cancer patients.
      DESIGN: Retrospective study. SETTING: Private hospital, Hong Kong. PATIENTS:
      Consecutive patients (702 in all) referred to the hospital with newly diagnosed
      breast cancer over the 5-year period from 2001 to 2006. MAIN OUTCOME MEASURES:
      Methods of detection; tumour size, lymph node involvement, and surgical treatment
      modalities. RESULTS: Over 80% of these patients presented following self
      discovery of a breast mass, whereas routine mammography accounted for only 8%.
      Screen-detected tumours were smaller than self-discovered tumours (2.02 vs 2.35
      cm, P<0.03), and mastectomy rates were lower in mammogram-screened patients than
      in self-discovered disease (35% vs 50%; P=0.03). In addition, self-detected
      tumours were significantly more likely to be associated with lymph node
      involvement than screen-detected tumours (38% vs 20%; P=0.007), confirming a
      prognostic difference. These uncontrolled data should not be interpreted as
      proving either the efficacy or the cost-effectiveness of breast screening.
      CONCLUSION: The findings suggest a disturbingly low utilisation of mammography in
      Hong Kong patients, and raise the possibility of a more proactive public health
      approach to promote such screening for susceptible target groups.

PMID- 17548908
TI  - Universal antenatal human immunodeficiency virus (HIV) testing programme is cost
      effective despite a low HIV prevalence in Hong Kong.
AB  - OBJECTIVE: To evaluate the cost-effectiveness of universal antenatal human
      immunodeficiency virus (HIV) testing in Hong Kong. DESIGN: Cost-effectiveness
      analysis from the health care provider's perspective. SETTING: Public antenatal
      clinics in Hong Kong. PARTICIPANTS: All pregnant women who gave birth in Hong
      Kong during the inclusive period 1 September 2001 and 31 December 2004. MAIN
      OUTCOME MEASURES: The primary endpoints were (i) the cost per HIV infection
      avoided and (ii) the cost per life-year gained. RESULTS: From 2001 to 2004, a
      total of 160,878 deliveries were recorded in Hong Kong; and 75% of the
      corresponding women had HIV testing before delivery. In all, 28 women tested HIV
      positive and gave birth to 15 babies, one of which was HIV-positive. The mother
      of the infected baby presented late in labour, without her HIV status being
      diagnosed and thus missed the opportunity for prompt intervention. Assuming a
      natural transmission rate of 25%, it was estimated that six out of seven
      anticipated HIV infections among the newborns had been avoided. The cost for
      implementation of the programme for the first 3 years was HKD12 227 988. Hence,
      the average costs per HIV infection averted and per discounted life-year gained
      were HKD2 037 998 and HKD79 099, respectively. Sensitivity analysis showed that
      both the coverage and the loss-to-follow-up rate were the major determinants of
      the cost-effectiveness of the universal antenatal testing programme in Hong Kong.
      CONCLUSION: The universal antenatal testing programme in Hong Kong is largely
      efficient. In view of the low prevalence of HIV infection, high rates of HIV
      testing and uptake of antiretroviral prophylaxis are crucial to the success of
      the programme.

PMID- 17548909
TI  - A questionnaire survey on patients' attitudes towards epidural analgesia in
      labour.
AB  - OBJECTIVES: To evaluate patient attitudes about epidural services in labour and
      correlate them with patient options and actual usage of epidural analgesia.
      DESIGN: Questionnaire survey. SETTING: Eight Hospital Authority obstetrics units.
      PARTICIPANTS: A cohort of new antenatal patients and a cohort of postnatal in
      patients over 1 calendar month. MAIN OUTCOME MEASURES: Antenatal patient
      awareness of epidural services and attitudes towards epidural analgesia during
      labour; the actual usage of such analgesia and the reported experience of
      postnatal patients. RESULTS: A total of 2109 and 2851 patients completed the
      antenatal and postnatal survey, respectively. The former revealed that only 47%
      of patients had been exposed to the concept of epidural analgesia in labour, and
      only 13% opted for such analgesia. In the postnatal cohort, the overall epidural
      analgesia rate was 10%, although 19% had actually requested it. Patients who
      received epidural analgesia in labour were more likely to consider their
      experience as favourable (85%) compared to those who went through labour without
      such analgesia (26%) [P<0.001]. There was no significant improvement in knowledge
      about epidural analgesia among postnatal as compared to antenatal patients. The
      main reasons generally ascribed by patients for not being able to obtain an
      epidural service despite it being requested, were related to limited resources.
      CONCLUSION: The results showed poor general awareness of pregnant women about the
      proper role of epidural analgesia in labour, leading to a low patient demand for
      such services. Despite the low prevailing request rate for epidural analgesia in
      labour, there appears to be a lack of adequate resources to meet the demand.

PMID- 17548910
TI  - Adulteration of over-the-counter slimming products with pharmaceutical analogue-
      an emerging threat.
AB  - OBJECTIVES: To review pharmaceutical analogue adulteration of non-prescription
      slimming products. DESIGN: Retrospective study. SETTING: Tertiary referral centre
      for toxicology analysis, Hong Kong. PATIENTS: All patients known to have been
      hospitalised after taking slimming products adulterated with pharmaceutical
      analogues from September 2004 to December 2006. MAIN OUTCOME MEASURES: Age,
      reasons for hospital admission, major biochemical findings, and toxicology
      analysis results of the offending slimming products. RESULTS: N
      nitrosofenfluramine, an analogue of fenfluramine with hepatotoxic effect, was
      found in two slimming products. Three patients were hospitalised after taking
      these slimming products, one of whom developed liver failure treated by liver
      transplantation. Another slimming product was found to contain N-desmethyl
      sibutramine, an analogue of sibutramine. A patient with an unremarkable medical
      history developed acute psychosis after taking the latter product for 1 week.
      CONCLUSIONS: Analogues, created by modifying the chemical structures of
      pharmaceuticals, are used as adulterants in non-prescription slimming products,
      in an attempt to evade regulatory inspection. The imperceptible use of these
      analogues is very dangerous because they have not been tested formally for
      efficacy and safety. In view of the potential harm to the public, more effective
      and proactive measures are required to guard against the illicit use of
      pharmaceutical analogues. There is also a need for increased awareness among the
      public and the medical professionals about this emerging threat.

PMID- 17548911
TI  - Delayed presentation and treatment of newly diagnosed pulmonary tuberculosis
      patients in Hong Kong.
AB  - OBJECTIVE: To measure patients' and providers' delays in the presentation and
      treatment of newly diagnosed pulmonary tuberculosis. DESIGN: Retrospective study
      using structured questionnaires. SETTING: Tuberculosis and Chest Service, Centre
      of Health Protection, Department of Health. PARTICIPANTS: Tuberculosis patients
      notified to the Department of Health, selected by systematic sampling of all
      notifications in the first 2 weeks of every even month in the year 2004. MAIN
      OUTCOME MEASURES: Health-seeking behaviour of pulmonary tuberculosis patients,
      including respective demographic, clinical, and disease factors. RESULTS: Of a
      total of 6262 notified tuberculosis patients in 2004, 1662 (26.5%) were recruited
      into the study; of these, 42.6% first presented to private doctors, and 57.4% to
      the public sector. The diagnosis of tuberculosis was made in 13.7% of these
      patients by the former and 86.3% by the latter. The median patient delay (elapsed
      time from symptoms to medical consultation) and provider delay (elapsed time from
      medical consultation to treatment) were both 20 days; 25th to 75th percentiles
      being 7-37 and 6-55 days, respectively. Longer patient delay was associated with
      positive sputum smear and culture, and more extensive radiological disease. On
      multiple regression analysis, unemployment independently predicted longer patient
      delay, while haemoptysis predicted shorter patient and total delay. Patients
      older than 60 years, with no initial sputum and chest X-ray examination predicted
      longer provider and total delays. CONCLUSIONS: Our patient and provider delays
      compared favourably with those of other countries, and very likely reflect easy
      service access. Adverse social factors and non-specific presentations prolong
      patient delay, whilst older age and unavailable bacteriological/radiological
      evidence delay diagnosis and treatment.

PMID- 17548912
TI  - Diagnostic value and safety of long-term video-EEG monitoring.
AB  - This paper aimed to assess the usefulness and safety of video-EEG (video
      electroencephalography) monitoring in patients with refractory epilepsy. We
      analysed the video-EEG recordings of consecutive patients over a 3-year period
      from 2002 to 2005. The pre-admission diagnosis, demographic information, number
      of ictal episodes, adverse events, and final diagnosis were recorded in all
      patients. The diagnostic labels before and after monitoring were compared in
      order to assess whether it had led to a change in diagnosis and management. Of
      the 100 patients who underwent video-EEG, 227 clinical events were recorded in 62
      cases. The most common events were complex partial seizures followed by non
      epileptic attacks. Video-EEG allowed a diagnosis to be made in 81 patients and
      the diagnosis at discharge was altered in 19 cases. Major injuries and status
      epilepticus did not occur during monitoring. In our experience video-EEG is safe
      and provides important clinical information in over 80% of patients.

PMID- 17548913
TI  - Two cases of postmaturity-related perinatal mortality in non-local expectant
      mothers.
AB  - We present two cases of postmaturity-related perinatal mortality with delivery at
      42 weeks 6 days' and 44 weeks' gestation, respectively. No cause beyond
      postmaturity was found. Neither induction of labour nor foetal monitoring had
      been performed despite these gestations going post 41 weeks because of a current
      'social obstetrics' phenomenon--non-local expectant mothers coming to Hong Kong
      from mainland China for delivery.

PMID- 17548914
TI  - Non-typhoid Salmonella mycotic aneurysm of the aortic arch.
AB  - Salmonella mycotic aneurysm is a rare but potentially fatal condition. Mortality
      is high without timely intervention. The clinical presentation is protean and
      early diagnosis requires a high degree of clinical alertness. Prompt surgical
      intervention and prolonged antimicrobial therapy are keys to successful
      treatment. We report an 81-year-old man with an atypical presentation of
      Salmonella mycotic aneurysm in the aortic arch. The case highlights the need to
      evaluate all patients over 50 years with non-typhoid Salmonella bacteraemia for
      possible endovascular infections. Contrast-enhanced computed tomography is useful
      for making an early diagnosis of this disease.

PMID- 17548915
TI  - Orbital involvement in Erdheim-Chester disease.
AB  - Erdheim-Chester disease is a rare, idiopathic, non-Langerhans' cell, histiocytic
      disorder. To our knowledge this is only the second case of Erdheim-Chester
      disease reported in the Chinese population. We describe a 45-year-old woman
      presenting with unilateral proptosis and periorbital xanthelasma.
      Histopathological examination revealed a xanthogranulomatous lesion expressing
      CD68, but negative for S100 protein, CD1a, CD3, or CD20. Systemic involvement was
      evident on bone scanning, and involvement of the thorax and abdominal aorta was
      seen on computed tomography. Despite treatment with systemic steroids,
      immunosuppressants, chemotherapy and interferon, progressive deterioration
      occurred. Our patient's clinical course was consistent with reports in the
      literature. Unfortunately, our patient developed neutropenic fever and died from
      septicaemic shock. Although Erdheim-Chester disease is a rare entity, especially
      in the Chinese population, an unusual presentation with orbital masses and
      bilateral xanthelasma, associated with systemic features, should raise the
      suspicion of this serious and potentially fatal disease.

PMID- 17548916
TI  - Unusual eye signs in Wegener's granulomatosis.
AB  - Wegener's granulomatosis is a rare necrotising vasculitis not easily diagnosed
      due to the obscurity of its diverse clinical features. Despite its comparatively
      low incidence, the unusual ophthalmic manifestations seen in this disease warrant
      extra caution from attending rheumatologists. In this case, bilateral peripheral
      ulcerative keratitis preceded any systemic symptoms. Timely recognition of the
      significance of this ophthalmic complaint and prompt ophthalmological
      consultation can help achieve early diagnosis and treatment of this potentially
      fatal rheumatological disease.

PMID- 17548917
TI  - Paget-Schroetter syndrome.
AB  - Paget-Schroetter syndrome, or 'effort' thrombosis of the axillary-subclavian
      vein, is an uncommon deep vein thrombosis usually caused by excessive upper limb
      activity. It may cause post-thrombotic syndrome, leading to significant
      disability if not treated appropriately. The optimal management for this syndrome
      is still controversial because the outcomes of different treatment strategies are
      based on case studies and series in small numbers. We report a case of Paget
      Schroetter syndrome in a young male weight-lifter and discuss treatment
      strategies suggested by the current literature.

PMID- 17548918
TI  - Dog bite wounds in a child.

PMID- 17548919
TI  - Re: Practice of breastfeeding and factors that affect breastfeeding in Hong Kong.

PMID- 17548921
TI  - Typhoid osteomyelitis of the spine.

PMID- 17548920
TI  - Gastro-intestinal stromal tumours in Hong Kong.

PMID- 17548922
TI  - [Epidemiology of idiopathic osteonecrosis of the femoral head in Japan].
AB  - The Ministry of Health, Labour and Welfare (MHLW) designates idiopathic
      osteonecrosis of the femoral head (ION) as so-called "intractable diseases" and
      has been promoting research. To summarize descriptive or analytic epidemiology of
      the ION in Japan, we present findings obtained through nationwide studies with
      the support of MHLW.

PMID- 17548923
TI  - [Diagnostic criteria, staging system and classification of idiopathic
      osteonecrosis of the femoral head].
AB  - Five criteria which showed high specificity were selected as follows. 1) collapse
      of the femoral head or crescent sign, 2) demarcating sclelosis in the femoral
      head, 3) cold in hot in bone scan, 4) band -like pattern on T1 weighted image of
      magnetic resonance imaging (MRI) , 5) trabecular and marrow necrosis on
      histology. Definite idiopathic osteonecrosis of the femoral head (ION) is
      diagnosed by fulfilling any two of the five criteria. Staging is judged on both
      AP and lateral X-ray. Stage 1 is defined as a period of no abnormality on X-ray.
      Stage 2is a period of demarcating sclelosis seen in X-ray. Stage 3 is a period of
      collapse of the head. Stage 3 is subclassified into Stage 3A when collapse is
      less than 3mm and 3B when collapse is 3mm or more. Stage 4 is a period of
      osteoarthritic changes. According to location of necrotic lesion on T1 weighted
      images or on x-ray, the lesions are classified into into four types. Type A
      lesion is defined to occupy medial one third or less of weight bearing portion.
      Type B lesion is defined to occupy medial two third or less of weight bearing
      surface. Type C1 lesion is defined to occupy more than medial two third, but not
      beyond acetabular edge while Type C2 lesion is defined to extend lateral to the
      acetabular edge.

PMID- 17548924
TI  - [Clinical condition of steroid-induced osteonecrosis of the femoral head].
AB  - Steroid-induced osteonecrosis of the femoral head (steroid-induced ONF) is an
      aseptic and ischemic disease developing after steroid therapy. Functions of hip
      joint are markedly disturbed when collapse is developed on the femoral head.
      Steroid-induced ONF accounted for the majority of the ONF. The occurrence
      mechanism is unknown, and prevention methods and fundamental remedies remain to
      be established. The timing of the occurrence of steroid-induced ONF is within
      several months after steroid administration. During the continuous steroid
      administration, no expansion of necrotic area was found. Recurrence was not also
      noticed. Patients have no symptoms when steroid-induced ONF occurs due to the
      establishment of ischemic conditions, and pain appears when the collapse of
      femoral head develops. There is an interval of several months or years between
      the occurrence of ONF and the onset of symptoms. Generally, conservative
      treatment is chosen during the asymptomatic period, and surgical treatment is
      considered after the symptoms appear. Appropriate screening and early detection
      are important to rational remedy for steroid-induced ONF.

PMID- 17548925
TI  - [Glucocorticoid-induced reduction in NO bioavailability and vascular endothelial
      dysfunction].
AB  - Glucocorticoid excess enhances superoxide-induced inactivation of nitric oxide
      (NO) and suppresses NO production through decreasing the expression of
      endothelial NO synthase. Glucocorticoid-induced decrease in NO bioavailability
      elicits vasuclar endothelial dysfunction, leading to insufficiency of peripheral
      circulation, which may be the pathogenesis for idiopathic osteonecrosis of the
      femoral head (ION) . Glucocorticoid-induced vascular endothelial dysfunction is
      the major therapeutic target for ION. NO causes overproduction of reactive oxygen
      species.

PMID- 17548926
TI  - [Vascular injury by glucocorticoid; involvement of apoptosis of endothelial
      cells].
AB  - Idiopathic osteonecrosis of the femoral head (IONF) is known to be caused by
      tissue ischemia, which is mainly associated with high-dose glucocorticoid (GC)
      used for the treatments of systemic autoimmune diseases. However, precise
      pathological mechanisms of IONF remain unclear. We first found that hypoxia
      inducible factor (HIF) -1alpha, a major transcription factor rapidly induced
      under hypoxic conditions, was highly expressed on endothelial cells of femoral
      head in patients with IONF. Transfection of HIF-1alpha induced p21-mediated
      arrest of cell cycle and subsequent apoptosis in endothelial cells. High dose GC
      also induced cell cycle arrest and apoptosis. Furthermore, there were additional
      effects between HIF-1alpha and high dose GC for the growth arrests and apoptosis
      of the cells. However, C-type natriuretic peptide (CNP) inhibited both cell cycle
      arrest and apoptosis of the endothelial cells in a concentration-dependent
      manner. There results indicate that hypoxia and high-dose GC play a pivotal role
      for vascular injury and that CNP could have a potential to protect the vascular
      injury seen in patients with IONF.

PMID- 17548927
TI  - [Animal models for steroid-induced osteonecrosis].
AB  - We describe that high-dose methylprednisolone (20 mg/kg) can induce multifocal
      osteonecrosis (ON) in conjunction with thrombocytopenia, hypofibrinogenemia, and
      hyperlipemia. Detailed clinical and laboratory evaluations of coagulation system
      are recommended in those patients who develop manifestations of an abnormal lipid
      metabolism shortly after high-dose corticosteroid therapy. Moreover, we
      investigated the effects of the combination treatment with an anticoagulant
      (warfarin) plus a lipid-lowering agent (probucol) on prevention of steroid
      induced osteonecrosis (ON) in this animal model. The incidence of ON in warfarin
      plus probucol (5%) was significantly lower than that observed in the control
      group (70%) (p <0.0001). Our results experimentally showed that the combined use
      of an anticoagulant and a lipid-lowering agent helps prevent steroid-induced ON
      in rabbits.

PMID- 17548928
TI  - [Oxidative stress on idiopathic osteonecrosis].
AB  - The increasing incidence of steroid-induced osteonecrosis of the femoral head is
      a recent and emerging problem. In-depth pathogenesis, however, has not been well
      understood. We focused on oxidative stress, which was reported to be involved in
      many diseases, and conducted animal studies to investigate it. Our results from
      the rabbit model of steroid-induced osteonecrosis demonstrated that
      administration of steroids caused oxidative damage in bones, and the
      administration of glutathione reduced the incidence of osteonecrosis. We were
      also the first to have successfully induced osteonecrosis in rats by
      administering buthionine sulfoximine (BSO) . The results indicated the
      involvement of oxidative stress in the development of osteonecrosis and may
      contribute to elucidating the underlying mechanisms and prevention of the
      pathogenesis of steroid-induced osteonecrosis.

PMID- 17548929
TI  - [Genetic analysis for prevention of steroid-induced osteonecrosis of the femoral
      head].
AB  - Idiopathic osteonecrosis of the femoral head (ION) is caused by disruption of
      blood flow. This disease often occurs in association with steroid treatment. The
      pathology of corticosteroid-induced ION is unclear, although abnormalities in the
      coagulation and fibrinolytic systems or in the lipid metabolism have been
      reported to be involved. We found the differences of gene polymorphism
      frequencies of ATP-binding casette, sub-family B, member 1 (ABCB1) C3435T,
      Apolipoprotein B (ApoB) C7623T and cAMP-response element binding protein-binding
      protein (CBP) (rs3751845) between ION cases and referent patients among those who
      were subjected to renal transplantation. For the prediction of ION, it is useful
      to analyze ABCB1 C3435T, ApoB C7623T and CBP (rs3751845) before the
      administration of steroids.

PMID- 17548930
TI  - [Hepatic CYP3A activity in association with development of osteonecrosis of the
      femoral head].
AB  - Osteonecrosis of the femoral head (ONFH) is one of the major side effects of
      corticosteroid therapy. Since corticosteroids are metabolized by hepatic
      cytochrome P450 3A (CYP3A), a low endogenous activity of this enzyme may exert
      excessive or toxic effect to bone and contribute to development of ONFH. To test
      this hypothesis, we measured hepatic CYP3A activity in 130 patients (26 with
      steroid-induced ONFH, 29 alcohol-related ONFH, and 75 normal controls without
      corticosteroid therapy and ONFH) by measuring the clearance of midazolam (MDZ) ,
      a substrate specific to CYP3A, and found that MDZ clearance in steroid-induced
      ONFH patients was significantly retarded when compared with that in controls or
      alcohol-related ONFH patients. Multivariate analysis revealed that only MDZ
      clearance was significantly related with steroid-induced ONFH and the patients
      with low MDZ clearance due to low hepatic CYP3A activity provided 9-fold greater
      risk for steroid-induced ONFH. Therefore, low hepatic CYP3A activity would be
      significant risk factor to the onset of steroid-induced ONFH.

PMID- 17548931
TI  - [Treatment of osteonecrosis of the femoral head with implantation of autologous
      bone-marrow mononuclear cells].
AB  - Idiopathic osteonecrosis of the femoral head commonly develops during adolescence
      and in the prime of adulthood. In Japan, joint-preserving procedures such as
      transtrochanteric rotational osteotomy, femoral varus osteotomy and vascularized
      bone grafting are often the surgical treatments of choice. However, the results
      of these procedures are not necessarily satisfactory. These procedures force
      patients to endure longer waits for their entire treatment. In addition, it is
      often difficult for surgeons to choose the appropriate treatment, especially in
      patients who have bilateral extensive osteonecrosis. We reported transplantation
      of bone marrow mononuclear cells for osteonecrosis of the femoral head and short
      term results.

PMID- 17548932
TI  - [MRI-based surgical simulation of transtrochanteric rotational osteotomy for
      osteonecrosis of the femoral head].
AB  - Transtrochanteric rotational osteotomy (TRO) is one of the joint-preserving
      surgical treatments for osteonecrosis of the femoral head (ONFH). It can prevent
      collapse of the femoral head as necrotic lesions in the weight-bearing portion
      can be moved sufficiently to less weight-bearing portion by anterior rotation,
      posterior rotation or varus angulation. Patient selection and preoperative
      planning are important to determine indications for TRO. It has been reported
      that successful TRO requires at least 34% of the weight-bearing area supported by
      the intact part of the femoral head. However, this ratio is difficult to
      preoperatively quantify according to the rotation angle using conventional two
      dimensional MR images or X-rays. Therefore, we developed a method of simulating
      TRO using three-dimensional (3-D) models reconstructed from 3-D MR images and
      applied it to serial patients with types C1 and C2 osteonecrosis at stage 1 or 2.
      The simulation visualized positional changes of the necrotic lesion in the weight
      bearing area and enabled quantitation of the postoperative intact ratio. Our
      surgical simulation is useful for evaluating the postoperative intact ratio and
      for determining indications for TRO as well as the optimal angle of femoral head
      rotation and varus angulation.

PMID- 17548933
TI  - [Transtrochanteric rotational osteotomy for the treatment of non-traumatic
      osteonecrosis of the femoral head].
AB  - Non-traumatic osteonecrosis involving the femoral head frequently occurs in young
      patients especially due to steroids administration or other some reasons. In
      cases of extensive lesion of the weight-bearing area, collapse is usually
      progressive. Preservation of the joint in young patients to avoid joint
      replacement procedures is important and widely accepted. Transtrochanteric
      rotational osteotomy for the femoral head osteonecrosis is ideal procedure moving
      the remained viable femoral head area to the loaded portion below the acetabular
      roof, thus hip joints can be preserved for long term by remodeling even if the
      stage is progressed preoperatively. This procedure is technically difficult, but
      should be common in orthopaedic surgeons.

PMID- 17548934
TI  - [Curved intertrochanteric varus osteotomy].
AB  - Curved intertrochanteric varus osteotomy is osteotomized between the lesser
      trochanter and the greater trochanter which is curved so as to place the femoral
      head in a varus position by rotating it in the coronal plane. After mean follow
      up of 5.4 years of 57 joints, approximately 98% of joints were preserved and 90%
      of joints were protected from the progression of disease. Curved
      intertrochanteric varus osteotomy can be used to preserve the hip joint in
      patients with osteonecrosis of the femoral head.

PMID- 17548935
TI  - [Hemiarthroplasty and total hip arthroplasty for idiopathic osteonecrosis of the
      femoral head].
AB  - Patients with idiopathic osteonecrosis of the femoral head (ION) are relatively
      younger (usually in their 30s to 50s) than those with osteoarthrosis (OA) , and
      usually have higher activity levels. When the necrotic area is large, or when
      advanced OA has developed, hemiarthroplasty or total hip arthroplasty (THA) are
      considered. When indicating these implant surgeries, age and life style of
      patients should be considered in selecting type of surgery and implant. In our
      previous study, THA was superior in durability to hemiarthroplasty in the entire
      series of ION patients and in the patients with stage 2 or 3 ION (without
      secondary OA) . As implants used for these surgeries have been improved, we are
      currently monitoring these implant surgeries with special interest in their
      durability.

PMID- 17548937
TI  - [Secondary osteoporosis: Inhaled corticosteroids induced osteoporosis in
      respiratory diseases].
AB  - Inhalation and oral steroids therapy has been used in the management of asthma,
      chronic obstructive pulmonary disease (COPD) and interstitial lung disease. This
      article described the effects of inhaled corticosteroids on bone. Inhaled
      corticosteroids are the standard of therapy in asthma and are commonly prescribed
      for chronic obstructive pulmonary disease. Accumulating evidence suggests that
      the effect of inhaled corticosteroids on bone is not small. Recent studies have
      shown that long-term use of inhaled corticosteroid at moderate or high doses is
      also associated with increased risk for the effects of inhaled corticosteroids on
      bone. Older age, inmobility and steroid treatment are major risk factors of
      osteoporosis. Treatment with bisphosphonate will be recommended in these
      patients, so earlier prevention for corticosteroids induced osteoporosis is
      necessary at administration of inhaled corticosteroids.

PMID- 17548936
TI  - [Total Hip Arthroplasty after previous proximal femoral osteotomy].
AB  - It is technically difficult to perform total hip arthroplasty (THA) after
      osteotomy because the proximal femur may be deformed after primary osteotomy. For
      the deformity of femur, combination with femoral osteotomy should be performed.
      The results obtained on performing THA after osteotomy have been described by
      some investigators. The main reasons of failure were malposion of stem,
      intraoperative fracture, dislocation, nonunion, and infection. This paper treats
      regards to avert these complications.

PMID- 17548938
TI  - [Bone diseases with Pain: Femoral neck fracture].
AB  - Although it is obvious that femoral neck fracture shows the worst prognosis of
      the physical function among variously osteoporotic symptoms, it is true that the
      fracture is the most painful disease. The fracture is treated to recover the
      physical function, instead of relieving the pain. Femoral neck fracture is
      classified into medial fracture broken at the inside of the capsule of hip joint
      and lateral fracture broken at the outside. A foreign paper emphasized the
      efficacy of early surgical treatment to relieve the pain, but in late day,
      correct surgery under the control of complications is revealed to introduce a
      good physical function and low mortality in Japan, as almost all the patients
      with femoral neck fracture is 80 years old or over, and have variously severe
      complications. Even in the delayed operation, early intervention of
      rehabilitation leads lower mortality and better prognosis of physical function.
      Femoral neck fracture is recently treated by those advanced surgery and
      rehabilitation, but number of independent patient reduced by two third and one of
      bed-ridden patient increased by 2.5 times one year after the fracture. So it
      would be important that the occurrence of femoral neck fracture reduced by
      increase of bone strength, prevention of falls, and adaptation of hip protector.

PMID- 17548939
TI  - Effect of Tinospora cordifolia on gamma ray-induced perturbations in macrophages
      and splenocytes.
AB  - Tinospora cordifolia (RTc) has already been reported to protect whole-body
      lethally irradiated mice. This study has focussed on certain aspects of immuno
      competence, which are adversely affected by irradiation. This study included
      estimation of spleen size, cell count, DNA fragmentation and apoptosis in
      splenocytes. The adherence, spreading and phagocytic activities of macrophages
      were also assessed. Cytokines in serum and anti-oxidants in plasma were also
      estimated. Administration of RTc (200 mg/kg.b.wt.) one hour before irradiation
      showed recovery of spleen weight from 49% of control in irradiated group to 93%;
      apoptosis from 19% to 2.8%; DNA fragmentation from 43% to 20.4%; macrophage
      adherence form 75% of control to 120% and macrophage spread size from 8 microm to
      15 microm. RTc also stimulated proliferation in splenocytes in a dose-dependent
      manner. RTc administration before irradiation also increased levels of IL-1beta
      and GM-CSF levels, from 56 pg/ml and 53 pg/ml respectively in irradiated group to
      59 pg/ml and 63 pg/ml. Similarly, radiation-induced decrease of anti-oxidant
      potential of plasma (32 Fe(2+) equiv.) as compared to control (132 Fe(2+) equiv.)
      was countered by administration of RTc before irradiation (74.2 Fe(2+) equiv.)
      RTc treatment thus reveals several radio-protective mechanisms.

PMID- 17548940
TI  - Cell cycle checkpoint and apoptosis induction in glioblastoma cells and
      fibroblasts irradiated with carbon beam.
AB  - This study was conducted in order to evaluate the cytotoxicity of high linear
      energy-transfer (LET) ionizing radiation (IR) on glioblastoma cells and
      fibroblasts using different modes of cell inactivation assays. Two human
      glioblastoma cell lines with or without p53-mutation, and fibroblasts were used
      as materials. Gamma rays and 290 MeV/u carbon beams with LET values of 20, 40, 80
      keV/mum were used. To evaluate cell inactivation, we used colony formation assay,
      morphological detection of apoptosis, and flow-cytometry. Serial expressions of
      p53 and p21 were analyzed by immunoblotting. High-LET IR reduced the reproductive
      potency of these cells to identical levels in spite of differences in gamma
      sensitivity, and yield of cell death correlated to LET values. A p53-wild-type
      glioblastoma cell line demonstrated a higher yield of apoptosis than other cell
      lines, whereas fibroblasts hardly displayed any cell death indicating senescence
      like growth arrest even after high LET IR. A p53-mutant tumor cell line
      demonstrated very low yield of cell death with prominent G2/M arrest. Results of
      radiosensitivity differ according to what mode of cell inactivation is selected.
      While fibroblasts depend on G1 block after IR, G2/M blocks may play crucial roles
      in the radioresistance of p53-mutant glioblastoma cells.

PMID- 17548941
TI  - Low dose radiation increased the therapeutic efficacy of cyclophosphamide on
      S(180) sarcoma bearing mice.
AB  - We examined whether low dose radiation (LDR) exposure (75 mGy) could increase the
      therapeutic efficacy of cyclophosphamide (CTX) by comparing the effects of tumor
      suppression, tumor cell apoptosis, cell cycle and proliferation of bone marrow in
      vivo. Kunming mice implanted with S(180) sarcoma cells were given 75 mGy whole
      body gamma-ray radiation exposure and CTX (300 mg/kg) by intraperitoneal
      injection 36 hours after LDR. Proliferation of bone marrow and tumor cells was
      analyzed by flow cytometry. Cytochrome c leakage from the tumor was measured by
      Western-blot. We discovered that tumor growth was significantly reduced in the
      group exposed to CTX add to LDR. The apoptosis of tumor cells increased
      significantly after LDR. The tumor cells were arrested in G(1) phase in the
      groups treated with CTX and CTX + LDR, but cell cycle was more significantly
      arrested in mice exposed to LDR followed by CTX than in mice exposed only to LDR
      or CTX chemotherapy. Concentration of bone marrow cells and proliferation index
      in CTX + LDR mice were higher than those in the untreated mice. LDR or CTX + LDR
      could induce greater cytochrome c levels and caspase-3 activity in tumors. These
      results suggest that low dose radiation can enhance the anti-tumor effect of the
      chemotherapy agent CTX markedly. Furthermore, LDR significantly protects
      hematopoetic function of the bone marrow, which is of practical significance on
      adjuvant chemotherapy.

PMID- 17548942
TI  - [Endoscopic treatment in the upper gastrointestinal tract: emergency endoscopy
      and endoscopic resection in the stomach].

PMID- 17548943
TI  - [Endoscopic diagnosis of tissue atypia and cancer invasive depth in the pharynx
      and esophagus using NBI enhanced imaging technology].

PMID- 17548944
TI  - [Clinical application of magnification endoscopy with NBI for diagnosis of early
      gastric cancer].

PMID- 17548945
TI  - [Usefulness of contrast-enhanced ultrasonography in the differential diagnosis of
      polypoid gallbladder lesions].
AB  - We investigated the usefulness of contrast-enhanced ultrasonography for
      differential diagnosis of polypoid gallbladder lesions in 60 patients, consisting
      of gallbladder carcinoma in 20, adenoma in 2, benign polyp in 29, and
      adenomyomatosis in 9, comparing contrast enhancement patterns with pathologic
      findings. We monitored vascular flow for 120 sec, constructing a time intensity
      curve (TIC) by flash-echo imaging. We compared the number of vessels and vessel
      diameter determined by contrast enhancement patterns and by pathologic
      examination. Contrast enhancement patterns were classified as linear, scattered,
      diffuse, or branched. When diffuse type and branched type were considered as
      indicative of cancer, accuracy was 84.5%, sensitivity 100%, and specificity
      76.9%. In gallbladder carcinoma, the TIC rose from no contrast to early-phase
      contrast sooner than in other diseases. In adenocarcinoma, high-intensity values
      persisted at 120 sec. With an intensity of 90 or greater at 120 sec taken as
      indicating cancer, accuracy was 89.7%, sensitivity 89.5%, and specificity 89.7%;
      Vessels were significantly more numerous in diffuse type cases than in those with
      other patterns. Vessel diameter was greatest in the diffuse type and the branched
      type patterns, both differing significantly from the linear type.
      Ultrasonographic contrast enhancement patterns show characteristic associations
      with pathologic findings and serve as valuable adjuncts in the diagnosis of
      gallbladder diseases.

PMID- 17548946
TI  - [Two cases of C1INH deficiency with paroxysmal abdominal pain].
AB  - We encountered two cases of C1 inhibitor deficiency (26-year-old man and 29-year
      old woman). They had been suffering from paroxysmal abdominal pain for many
      years. Imaging studies showed wall thickening of the intestine and ascites and
      diagnosis was difficult. Decreased serum levels of C4 and C1INH activity
      indicated a diagnosis of C1INH deficiency. Although C1INH deficiency is rare, it
      should be considered as a differential diagnosis in young patients with
      paroxysmal abdominal pain.

PMID- 17548947
TI  - [A case of mesenteric desmoid tumor].
AB  - A 53-year-old man was admitted hospital because of frequent vomiting and poor
      digestion. Abdominal computed tomography showed a tumor, about 5 cm in diameter
      at the duodeno-jejunal junction. A barium contrast duodeno-small bowel series
      revealed stenosis in the therd portion, where push enteroscopy could not pass
      with normal mucosa. The preoperative diagnosis was submucosal or mesenteric
      tumor. Open surgery was performed. The tumor derived from the mesenterium and
      involved the anal side of the small intestine. The tumor was removed with partial
      excision of the upper jejunum. The diagnosis of mesenteric desmoid tumor was
      confirmed, histologically.

PMID- 17548948
TI  - [Hepatocellular carcinoma occurring after 11 year-long sustained viral response
      to interferon therapy for chronic hepatitis C].
AB  - The patient was a 61-year-old man with chronic hepatitis C who achieved a
      sustained virological response to interferon therapy in 1993. As a result, the
      status of his liver improved pathologically from F2A2 to F1A1. Eleven years
      later, however, a tumor measuring 15 mm in diameter in segment 6 of the liver was
      indicated by CT. A well-differentiated hepatocellular carcinoma was detected by a
      fine needle biopsy. The lesion was treated by transcatheter arterial
      chemoembolization combined with radiofrequency ablation. Even if patients with
      chronic hepatitis C have achieved a sustained virological response to interferon
      therapy, patients with risk factors for the development of hepatocellular
      carcinoma, such as being a male of advanced age and with progressive fibrosis of
      the liver, should receive careful long-term follow-up.

PMID- 17548949
TI  - [A case of peripheral facial nerve palsy with cryoglobulinemia and chronic
      thyroiditis occurring during interferon plus ribavirin therapy for chronic
      hepatitis C].
AB  - A 42-year-old woman with chronic hepatitis C has visited our hospital since
      October 2003. Liver biopsy revealed chronic hepatitis (A1/F1) . Therapy was
      initiated with interferon (IFN) alpha-2b and ribavirin in February 2004. Two
      months later, the patient developed left facial weakness. Laboratory findings
      showed cryoglobulinemia and abnormal thyroid function without any evidence of
      other viral infections. Idiopathic peripheral facial nerve palsy was diagnosed.
      IFN was discontinued at week 9 of therapy, but she obtained sustained virological
      response and her symptoms resolved at 6 month after the withdrawal.

PMID- 17548950
TI  - [A case of portal vein thrombosis associated with congenital protein S
      deficiency].
AB  - A 25-year-old man was admitted to our hospital because of abdominal pain, nausea
      and low-grade fever. An abdominal CT showed remarkable thickening of the wall of
      the small intestine and extensive thrombosis of the mesenteric, portal and
      splenic veins. Because neither intestinal infarction nor peritonitis was seen,
      anticoagulation therapy was chosen. Heparin was administered intravenously and
      was used alternatively with warfarin later. The patient's symptoms and clinical
      data improved gradually. Concerning the etiological factors of the thrombosis,
      only protein S activity definitely decreased. Genetic analysis indicated a
      variant of protein S, protein S Tokushima.

PMID- 17548951
TI  - [A case of mixed duct-islet cell tumor of the pancreas].
AB  - A 30-year-old woman was referred to us because of hypoglycemic attack. The tumor
      on the pancreatic body of 22 mm size was revealed by close inspection, and was
      diagnosed as insulinoma. Surgical resection was performed, but curative resection
      was impossible because the component of adenocarcinoma infiltrating into
      surrounding tissue coexisted with insulinoma. Postoperatively, we make a
      diagnosis of combined tumor of the pancreas, i.e. mixed duct-islet cell
      carcinoma. In this paper, we discuss this rare disorder and summarize 33 cases
      reported in the Japanese literature.

PMID- 17548952
TI  - [A case of nodule-in-nodule type HCC presenting corona enhancement within the
      outer tumor on single-level dynamic CT during hepatic arteriography].

PMID- 17548953
TI  - A palatinose-based balanced formula improves glucose tolerance, serum free fatty
      acid levels and body fat composition.
AB  - Palatinose is a disaccharide present in honey, which has the characteristics of
      delayed digestion and absorption. We developed a palatinose-based balanced
      formula (PBF) and reported its beneficial effects on metabolic syndrome-related
      parameters in rats. To examine the effects of PBF in humans, we here conducted a
      crossover study using twenty-three subjects with impaired glucose tolerance. The
      subjects were divided into two groups: intervention to control (I/C) and control
      to intervention (C/I) groups. The I/C group consumed PBF (250 kcal) together with
      foods that were 250 kcal less than their usual breakfast (intervention meal) for
      the first 12 weeks, followed by their usual breakfast (control meal) for the last
      12 weeks. The protocol for the C/I group was opposite in order: the control meal
      for the first 12 weeks, followed by the intervention meal for the last 12 weeks.
      In the first 12-week period, the intervention meal decreased 2-hr plasma glucose
      levels after 75-g oral glucose tolerance test (-15.7 +/- 20.1% change), while the
      control meal did not (0.8 +/- 31.6% change). The difference between these changes
      was significant (p = 0.038). The similar results were obtained from the
      comparison of the changes between the first and the last 12-week periods in the
      two groups combined (intervention vs control: -11.8 +/- 22.5 vs 11.2 +/- 30.2%
      change, p = 0.024). PBF also had the beneficial effects on serum free fatty acids
      levels and visceral fat area. In conclusion, PBF consumption has beneficial
      effects on metabolic syndrome-related parameters in humans.

PMID- 17548954
TI  - Detection, enumeration and characterization of T helper cells secreting type 1
      and type 2 cytokines in patients with recurrent aphthous stomatitis.
AB  - One of the factors involved in the pathogenesis of recurrent aphthous stomatitis
      (RAS) is a cell-mediated immune response in which several cytokines seem to play
      a major role. The aim of this study was to detect, enumerate and characterize T
      helper cells which are secreting type 1 cytokines (interleukin [IL]-2, IL-12,
      interferon [IFN]-gamma, and tumor necrosis factor [TNF]-alpha) and type 2
      cytokines (IL-4, IL-5, IL-6, and IL-10) in the peripheral blood of patients with
      RAS. Thirty-two patients in the active phase of RAS (14 men and 18 women) and 40
      healthy individuals participated in the study. T helper (T) cells were detected
      and characterized using Elispot assay. T cells secreting IL-2, IL-12 or IFN-gamma
      were increased in patients with RAS compared with the controls (p < 0.05, p <
      0.001 and p < 0.001, respectively). T cells secreting TNF-alpha in RAS patients
      and controls were not statistically different (p > 0.05). T cells secreting IL-10
      were increased in patients with RAS compared with the controls (p < 0.05). T
      cells secreting IL-4 were decreased in patients with RAS compared with the
      controls (p < 0.001), No statistical difference was observed between T cells
      secreting IL-5 or IL-6 in patients with RAS and controls. Our findings suggest
      that the increased numbers of T cells secreting type 1 cytokines may influence
      the immune response against RAS. Whether this action is of etiological importance
      or epigenetic phenomenon is a question that needs to be answered.

PMID- 17548955
TI  - Impact of glucose intolerance on coronary calcified lesions evaluated using
      multislice computed tomography.
AB  - Metabolic syndrome has the unique concept that the common occurrence of
      individual disease components increases the risk of coronary artery disease
      (CAD). However, some studies suggest that the burden of different CAD risk
      factors is not equal, and focusing on the whole set of risk factors might neglect
      the impact of individual factors that could be useful targets for prophylactic
      therapies. The purpose of this study was to investigate the effect of glucose
      intolerance on CAD using multislice computed tomography (MSCT). Ninety-eight
      consecutive patients with at least one traditional CAD risk factor who visited a
      municipal hospital were enrolled in this study. The risk factors were impaired
      glucose tolerance (fasting glucose > or = 110 mg/dl or patients with diabetes),
      low high-density lipoprotein cholesterol (HDL-C, < 40 mg/dl for men and < or = 50
      mg/dl for women), hypertriglycemia (triglyceride > or = 150 mg/dl), hypertension
      (blood pressure > or = 130/85 mmHg), and obesity (body mass index, > 25 kg/m(2)
      for men and > 23 kg/m(2) for women). CAD was determined by the presence of either
      stenoses, non-calcified plaques or calcified lesions. The following risk factors
      were significantly related in univariate logistic models: glucose intolerance and
      coronary calcified lesions (p = 0.001), and hypertriglycemia and non-calcified
      plaque lesions (p = 0.048). Multivariate models showed that glucose intolerance
      was significantly associated with calcified lesions, even after adjustment for
      gender, age, low HDL-C, hypertriglycemia, hypertension, and obesity (p = 0.018).
      Our results suggest that glucose intolerance might be closely related to the
      presence of coronary calcified lesions among traditional CAD risk factors.

PMID- 17548956
TI  - Modulation of brachioradialis motoneuron excitabilities by group I fibers of the
      median nerve in humans.
AB  - Group I fibers from muscle spindles and Golgi tendon organs modulate motoneuron
      excitabilities to coordinate smooth movements. In this study, to elucidate the
      effects of group I fibers of the median nerve (MN) on the excitabilities of the
      brachioradialis (BR), we evaluated the changes in the firing probability of a BR
      motor unit after electrical conditioning stimulation (CS) to MN with a post
      stimulus time-histogram technique in six healthy human subjects. We tested 171
      motor units: in 72 of them CS to MN at the elbow with the intensity just below
      the threshold of alpha motor fibers (MT) produced a facilitatory effect
      (facilitation), while in 43 of them it produced inhibitory one (inhibition). The
      facilitation and inhibition were not produced by electrical stimulation of the
      skin overlaying MN. The central synaptic delays of the facilitation and
      inhibition were on average -0.13 and 0.13 msec, respectively, longer than those
      of the homonymous facilitation mediated by a monosynaptic path. The thresholds of
      the facilitation and inhibition were less than 0.7-0.8 and 0.7-0.9 times MT,
      respectively. CS to MN of hand muscles produced facilitatory effects and that of
      the pronator teres, palmaris longus, and flexor carpi radialis inhibitory
      effects. The facilitatory and inhibitory effects were compatible, for latency,
      with the facilitation and inhibition. These findings suggest that BR motoneurons
      receive monosynaptic facilitation and oligosynaptic inhibition from MN in humans.
      Group I fibers of the hand and forearm muscles should mediate the facilitation
      and inhibition, respectively, to coordinate movements of the hand, forearm, and
      elbow.

PMID- 17548958
TI  - Colonization and differentiation of transplanted embryonic stem cells in the
      irradiated intestine of mice.
AB  - Radiation-induced intestinal injury is a common complication in radiotherapy for
      the cancer located in abdomen or pelvis. However, there is no effective treatment
      for radiation-induced intestinal injury now. It is therefore important to develop
      new treatments for radiation-induced intestinal injury. In this study, we
      investigated whether embryonic stem (ES) cells could be transplanted directly
      into the radiation-damaged intestine and could colonize and differentiate into
      the intestinal epithelial cells. The intestines of female nude mice (ICR nu/nu)
      were irradiated at a single dose of 30 Gy, and were immediately transplanted with
      male 129/Sv-derived ES cells into the wall of the irradiated intestine by direct
      injection. The intestine was removed on days 13 to 27 after transplantation. The
      Y-chromosome DNA of transplanted ES cells in the irradiated intestine was
      determined by polymerase chain reaction. Colonization and differentiation of
      transplanted ES cells in the irradiated intestine were analyzed by histological
      and immunohistochemical methods with antibodies against stage-specific embryonic
      antigen-1, alpha-smooth muscle actin and cytokeratin AE1/AE3. The cells of donor
      origin were identified in the intestine of irradiated mice, and intestinal crypt
      like structures were observed on day 13 after transplantation. Importantly, we
      observed that ES cells could differentiate into epithelial cells in the submucosa
      of irradiated intestine on day 13 and 27 after transplantation. These results
      suggest that transplanted ES cells could colonize and differentiate in the
      intestinal intestine. Such a new approach for damaged intestine with transplanted
      stem cells would be promising.

PMID- 17548957
TI  - Decreased total antioxidant response and increased oxidative stress in Behcet's
      disease.
AB  - Behcet's disease (BD) is a chronic systemic inflammatory disease. Inflammatory
      reactions trigger the oxidative stress and oxidants decrease the level of
      antioxidants. In the present study, we aimed to determine serum
      oxidative/antioxidative status in patients with BD. Serum antioxidative status
      was evaluated by measuring total antioxidant capacity (TAC), paraoxonase 1,
      arylesterase, sulfhydryl groups and ceruloplasmin in patients with BD and in
      healthy controls. Serum oxidative status was evaluated by measuring total
      peroxide (TP), lipid hydroperoxides and oxidative stress index (OSI). OSI was
      calculated by percent ratio of TP to TAC. Serum levels of TAC, sulfhydryl groups
      and activities of paraoxonase 1, arylesterase, and ceruloplasmin were
      significantly lower in patients than in controls (p < 0.001 for all). In
      contrast, TP, lipid hydroperoxides and OSI values were significantly higher in
      patients than in controls (p < 0.001 for all). Further, the level of TAC was
      negatively correlated with the levels of TP, lipid hydroperoxides and OSI both in
      the BD (r = -0.578, p < 0.01; r = -0.559, p < 0.01 and r = -0.552, p < 0.01,
      respectively) and the control groups (r = -0.469, p < 0.05; r = -0.351, p < 0.05
      and r = -0.391, p < 0.05, respectively). These results indicate that the oxidant
      parameters increased and antioxidant parameters decreased in patients with BD;
      therefore, these patients might have been exposed to oxidative stress. We suggest
      that impaired oxidant/antioxidant balance should be taken into consideration in
      the follow-up of patients with BD.

PMID- 17548959
TI  - Prenatal exposure to 3,3',4,4',5-pentachlorobiphenyl (PCB126) promotes anxiogenic
      behavior in rats.
AB  - Polychlorinated biphenyls (PCBs) are environmental contaminants that have adverse
      effects on the endocrine and nervous systems. As they are still detected in
      breast milk and adipose tissue in humans, the accumulated PCBs may transfer from
      mothers to children and damage central nervous system. It is revealed from
      epidemiological studies that cognitive and motor functions were damaged in
      children born to mothers who ingested PCBs-contaminated foods. However, it
      remains unclear whether prenatal exposure to PCBs affects emotionality. In the
      present study, we therefore examined the effect of prenatal exposure to
      3,3',4,4',5-pentachlorobiphenyl (PCB126) on emotionality in rats by focusing on
      anxiogenic behavior and response of the hypothalamus-pituitary-adrenal axis to
      stress. Pregnant rats were treated orally with PCB126 at a dose of 30 microg/kg
      or corn oil, its vehicle, on gestational day 15, and their male offspring were
      subjected to the following experiments at 4-5 weeks old. In an open field test,
      rats with prenatal exposure to PCB126 showed anxiogenic behavioral responses,
      including decrease in time spent in the center of an open field and the number of
      rearings and extension of grooming duration. Interactive behavior, which is an
      index of anxiety level, was shortened in the social interaction test. The
      increase in the serum corticosterone level induced by forced swim stress was
      facilitated by prenatal exposure to PCB126. This evidence suggests that PCB126
      may exert anxiogenicity on the offspring of exposed dams, and dysfunction of the
      hypothalamus-pituitary-adrenal axis may at least in part contribute to this
      abnormality.

PMID- 17548960
TI  - Quantitative correlation of Helicobacter pylori stool antigen (HpSA) test with
      the severity of H. pylori-related gastritis.
AB  - The Helicobacter pylori (H. pylori) load in both stomach and stool and the
      resulting severity of gastritis are important criteria in validating the status
      of H. pylori infection. We aimed to assess the reliability of the H. pylori stool
      antigen (HpSA) test for the primary diagnosis of H. pylori infection by
      calculating the best cut-off value to obtain the highest sensitivity and
      specificity in dyspeptic patients. We also investigated the correlation of HpSA
      test with the severity of gastritis and H. pylori load. The H. pylori statuses of
      95 patients were evaluated by the positivity of both rapid urease test and
      microscopic detection of H. pylori in biopsy specimens, 88 subjects of whom were
      H. pylori positive. The sensitivity and specificity of the HpSA test were 51.1%
      (45/88) and 100% (7/7), respectively, according to the manufacturer's recommended
      cut-off value of 0.16. However, with the best cut-off value of 0.048, calculated
      by receiver operator characteristics analysis, the sensitivity of the test
      increased to 92.0% (81/88) with the same specificity. High values of the HpSA
      test were correlated with high scores of corpus H. pylori load and the severity
      of antrum and corpus inflammation (p < 0.05). With the best cut-off value of the
      HpSA test, the primary diagnosis of H. pylori infection can be made with higher
      sensitivity and specificity. The HpSA test is a helpful tool that evaluates the
      severity of H. pylori infection and the degree of gastric inflammatory activity
      and gastric H. pylori load.

PMID- 17548961
TI  - Association between depression and anxiety symptoms and major atherosclerosis
      risk factors in patients with chest pain.
AB  - Psychological variables, such as depression and anxiety, are known as independent
      risk factors for coronary artery disease (CAD), suggesting the interaction of
      psychological and physiological factors in the development of CAD. In the present
      study, we analyzed the possible association between depressive and anxiety
      symptoms and major atherosclerotic risk factors in patients with chest pain
      warranting coronary angiography. The patients without CAD (n = 159) and those
      with CAD (n = 155) were evaluated for the severity of depression and anxiety by
      the symptom scales; high scores indicate severe symptoms. Age, male/female ratio,
      prevalence of diabetes mellitus (DM), and depression level were significantly
      higher in the CAD group. Among a total of 314 patients with chest pain, the mean
      depression score was higher in patients with DM (16.01 +/- 8.12 vs 13.01 +/- 9.6,
      p = 0.01) and those with hypercholesterolemia (15.43 +/- 9.61 vs 12.53 +/- 9.61,
      p = 0.02). The mean anxiety score was also higher in patients with DM (20.81 +/-
      12.85 vs 16.51 +/- 12.09, p = 0.008), hypercholesterolemia (20.67 +/- 13.11 vs
      15.29 +/- 11.36, p = 0.002), or hypertension (20.74 +/- 12.94 vs 14.1 +/- 10.8, p
      = 0.001). Thus, DM and hypercholesterolemia are associated with depression and
      anxiety, while hypertension is only related to anxiety. In contrast, smoking and
      family history of atherosclerosis are not related to depression and anxiety
      scores. These results suggest depression and anxiety symptoms may contribute to
      the development and progression of CAD, especially in patients with DM or
      hypercholesterolemia.

PMID- 17548962
TI  - Up-regulation of DNA-methyltransferase 3A expression is associated with
      hypomethylation of intron 25 in human testicular germ cell tumors.
AB  - From a developmental point of view, human testicular germ cell tumor (TGCT) can
      be traced back to the primordial germ cells in the embryo, which, upon
      transformation, become either seminoma or non-seminoma. Thus, TGCT provides a
      useful model system for the study of gene regulation involved in oncogenesis as
      well as development. In this study, we focused and analyzed the expression and
      epigenetic alteration of DNA-methyltransferase (DNMT) genes in TGCT tissues. The
      examined genes included DNMT1, DNMT3A and DNMT3B that function to maintain or
      generate a methylation status of genomic DNA. Using semi-quantitative reverse
      transcription-polymerase chain reaction, we found that the expression of DNMT3A,
      but not DNMT1 or DNMT3B, was up-regulated markedly in TGCT specimens compared to
      non-tumor testicular tissues. To explore mechanisms involved in the up-regulation
      of DNMT3A, we examined the methylation status of CpGs in the gene. The distal and
      proximal promoter regions of DNMT3A were non-methylated in both TGCT and non
      tumor tissues. In contrast, non-tumor testicular tissues exhibited a mixture of
      methylated and non-methylated CpGs in intron 25 of DNMT3A, whereas most CpGs in
      intron 25 were demethylated in TGCT specimens. This difference in the degree of
      methylation was confirmed by Southern blot analysis, in which an EcoRI site in
      intron 25 could be digested only when the CpG was non-methylated. Thus,
      epigenetic alteration of intron 25 toward de-methylation is associated with
      increased expression of DNMT3A in TGCT. The intron 25 may represent a
      differentially-methylated region in DNMT3A that is modulated during development
      and/or tumorigenesis of germ cells.

PMID- 17548963
TI  - Chemopreventive effect of selenium-enriched Japanese radish sprout against breast
      cancer induced by 7,12-dimethylbenz[a]anthracene in rats.
AB  - Breast cancer is one of the major cancers in women, and dietary intake must be
      controlled to prevent it. Selenium (Se), especially Se compound in vegetables, is
      thought to be a promising chemopreventive dietary ingredient for preventing
      breast cancer. In this study, we developed Se-enriched Japanese radish sprout
      using a special Se-additional fertilizer, and identified the Se chemical forms.
      The newly developed Se-enriched sprout is produced within a week by the tank
      forming method, and the major chemical form was identified as Se
      methylselenocysteine (MeSeCys) (80%). Then, the chemopreventive effects of the Se
      enriched sprout were investigated using Sprague-Dawley female rats with mammary
      cancer, induced by a single oral dose of 10 mg or 14 mg of 7, 12
      dimethylbenz[a]anthracene (DMBA). Mammary tumors were found in 11, 16 and 2 rats
      treated with DMBA and thereafter fed the basal (n = 34), sprout-added basal (n =
      30) and Se-enriched sprout-added test diets (n = 30), respectively. The incidence
      of mammary tumors was significantly lower in the Se-enriched sprout-added test
      diet group (7%) than in the basal diet group (32%) or sprout-added basal diet
      group (53%). In contrast, no significant difference was detected in the numbers
      and incidence of the tumor between the basal diet group and Se-enriched sprout
      added test diet group before DMBA-dosing. These results suggest that the diet
      supplement of Se-enriched sprout after DMBA-dosing provides a significant
      chemoprevention against chemical-induced mammary cancer. Thus, Se-enriched sprout
      may be a useful dietary ingredient for preventing breast cancer.

PMID- 17548964
TI  - Malignant lymphoma arising from heterotopic Warthin's tumor in the neck: case
      report and review of the literature.
AB  - Warthin's tumor (WT), so-called adenolymphoma, is a benign salivary gland tumor
      with both epithelial and lymphoid histological characteristics, so the
      histogenesis remains unclear. Treatment consists primarily of tumor removal or
      conservative follow up. Here we present a rare case of malignant lymphoma arising
      from heterotopic (ectopic) WT. A 102-year-old man presented with a mass in the
      left side of the neck which was painless but gradually enlarged over 1 month. The
      mass was 2-3 cm in diameter, and freely moveable below the angle of the mandible.
      The mass was totally removed. The histological diagnosis was malignant lymphoma,
      diffuse large B-cell type, arising from heterotopic WT. Postoperative staging
      examination including chest radiography, bone scan, and computed tomography of
      the abdomen and pelvis revealed no evidence of dissemination of malignant
      lymphoma. Malignant transformation within WT is rarer in the lymphoid component
      than in the epithelial component. Only 16 cases of malignant transformation
      arising from WT have been reported, including only three cases of non-Hodgkin
      lymphoma apparently arising from heterotopic WT. Tumor removal or careful follow
      up is recommended in patients with WT because of the potential risk posed by such
      malignant transformation.

PMID- 17548965
TI  - DDX39, upregulated in lung squamous cell cancer, displays RNA helicase activities
      and promotes cancer cell growth.
AB  - To explore differentially expressed genes involved in non-small cell lung cancer
      progression, we used the gene expression profile database of various human
      tissues and identified DDX39, a new member of the DEAD box RNA helicases, showing
      overexpression in human lung squamous cell carcinoma (LSCC) but not in lung
      adenocarcinoma (LAC). There existed three types of alternatively spliced DDX39
      variants (DDX39-L, -S and -SS), of which only DDX39-L contains all the motifs
      required for RNA helicase activity. RT-PCR analysis verified the increased
      expression of DDX39-L in LSCC, but not LAC, cultured cells compared with normal
      bronchial epithelial cells. A high sequence similarity to UAP56 and punctate
      nuclear localization pattern of DDX39-L suggest that it plays a role in RNA
      splicing/export. Recombinant DDX39-L binds RNA, hydrolyzes NTPs in an RNA
      dependent manner and unwinds double strand RNA bidirectionally, proving that
      DDX39 is an RNA helicase. Overexpression of DDX39-L stimulates colony formation
      of HeLa cells, probably through elevation of a translational level, indicating
      the biological significance of DDX39 in cancer pathogenesis. Thus, DDX39 is a
      novel RNA helicase capable of promoting cancer cell growth and, thereby, can be a
      potential target for development of a therapeutic strategy for LSCC.

PMID- 17548966
TI  - The management of hypertension in the African American patient.
AB  - A panel was convened to discuss the topic of the management of hypertension in
      the African American patient. Jackson T. Wright, MD, PhD, Professor of Medicine,
      Case Western Reserve University, Cleveland, OH, moderated the panel. Kenneth A.
      Jamerson, MD, Professor of Medicine, University of Michigan, Ann Arbor, MI, and
      Keith C. Ferdinand, MD, Association of Black Cardiologists, Inc, and Emory
      University, Atlanta, GA, participated in the discussion. This expert panel
      discussion was supported by Novartis and each author received an honorarium from
      Novartis for time and effort spent participating in the discussion and reviewing
      the transcript for important intellectual content prior to publication. The
      authors maintained full control of the discussion and the resulting content of
      this article; Novartis had no input in the choice of topic, speakers, or content.

PMID- 17548967
TI  - The persistence or the disintegration of memory: cognitive side effects of
      electroconvulsive therapy.

PMID- 17548968
TI  - Does bilateral ECT cause persistent cognitive impairment?

PMID- 17548970
TI  - Response to Drs Abrams and Kellner: the cognitive effects of ECT in community
      settings.

PMID- 17548969
TI  - Electroconvulsive therapy in a perfect world.

PMID- 17548971
TI  - Re: the cognitive effects of ECT in community settings.

PMID- 17548972
TI  - Levels of evidence, causality, and clinical significance.

PMID- 17548973
TI  - ECT generalized seizure drives heart rate above treadmill stress test maximum.
AB  - OBJECTIVES: Heart rate (HR) accelerates with the electroconvulsive therapy (ECT)
      seizure and decelerates when it ends. The peak HR during ECT seizure has been
      reported to reflect clinical impact. We aimed to identify the expected range for
      ECT peak HR and how it varies with age and sex, as a reference in clinical use.
      METHODS: We examined medical records for the maximum peak seizure HR over the ECT
      course for all ECT patients over defined periods at 2 clinical sites.
      Methohexital-succinylcholine anesthesia was usually used. Subject totals were 87
      men and 90 women. RESULTS: Electroconvulsive therapy peak HR was 140 to 180 bpm
      and did not fall with age through 80 years, separately for men and women. A few
      patients lay outside this cluster and showed age-related decrease. Overall and
      including the extreme elderly, peak HR fell by 0.29 bpm/yr. CONCLUSIONS:
      Electroconvulsive therapy seizure peak HR less than 140 bpm points to weakness of
      the ECT seizure (and need to increase stimulus dose), cardiac disease, or
      medication effect limiting HR. Electroconvulsive therapy peak HR exceeds
      treadmill exercise maximum HR after 60 years and falls significantly less with
      age than the 0.7 to 1 bpm/yr reported for maximum HR with treadmill exercise
      stress. These comparisons suggest that ECT peak HR and treadmill maximum HR are
      limited by different aspects of physiology, and that exercise HR is limited by
      metabolic demand and humoral activity rather than the heart itself.

PMID- 17548974
TI  - The influence of name on the acceptability of ECT: the importance of political
      correctness.
AB  - BACKGROUND: Attitudes toward a treatment influence the acceptability of the
      treatment. There has been no study of how attitudes toward electroconvulsive
      therapy (ECT) are influenced by what ECT is called. METHODS: A sample of 125
      laypersons was drawn from 3 social settings in Bangalore, India. A short, oral
      questionnaire was administered to determine the acceptability of ECT under 3
      different names: 2 actual and 1 coined. RESULTS: The acceptability of ECT was
      highest for the coined name electrostimulatory therapy (53%), intermediate for
      the occasionally used name electroshock therapy (38%), and least for the commonly
      used name electroconvulsive therapy (9%) (P < 0.001). Electrostimulatory therapy
      was the preferred choice because it was least associated with the likelihood of
      harm (P < 0.01). CONCLUSIONS: How a treatment is presented may influence
      reactions to it and, hence, its acceptability. We therefore suggest that ECT is
      better described as electrostimulatory therapy than as electroconvulsive therapy
      or electroshock therapy. We further suggest that discussions on ECT should
      emphasize the stimulatory effects of the treatment and downplay parallels with
      epilepsy. In an age of political correctness, political correctness should be
      applied to the description of ECT.

PMID- 17548975
TI  - Electroconvulsive therapy: the practice and training needs of referring
      psychiatrists in the United Kingdom and Republic of Ireland.
AB  - This study aims to gain a greater understanding of the clinical practice and
      training needs of psychiatrists who prescribe electroconvulsive therapy (ECT),
      including knowledge about ECT, obtaining informed consent, and the monitoring of
      patients after ECT. Four hundred ninety psychiatrists who refer patients for ECT
      were sent questionnaires as part of reviews conducted by the ECT Accreditation
      Service, and 56% responded. Data were analyzed using descriptive statistics and
      thematic analysis. Nearly all felt that they had adequate knowledge about ECT
      with 35% recognizing further training needs. Psychiatrists were likely to find
      difficulty explaining to patients more about how ECT works and the possibility of
      long-term cognitive side effects than the benefits of ECT. The main areas of
      training need are the obtaining of informed consent, including the choice between
      unilateral and bilateral ECT, and the assessment of cognitive function during and
      after the course. The study also reveals the need for further research into long
      term cognitive side effects of ECT and the need for a reliable cognitive
      assessment tool for measuring persistent or autobiographical memory deficits.

PMID- 17548976
TI  - Effects of an education training program on attitudes to electroconvulsive
      therapy.
AB  - Widespread negative attitudes toward electroconvulsive therapy (ECT) are present
      in the general public and among heath care professionals. However, there is
      evidence to suggest that clinical experience and knowledge of ECT positively
      improve attitudes toward this treatment. The purpose of this study was to
      evaluate the effects of an ECT education training program on attitudes toward
      ECT. Participants were 73 student nurses (91.8% women) and 21 care aid students
      (81.0% women) undertaking a 6-week rotation in psychiatry at a large provincial
      psychiatric hospital in British Columbia, Canada. The ECT education training
      program consisted of a brief lecture, viewing of an educational videotape,
      familiarization with the ECT equipment, and observation of an ECT treatment.
      Participants completed a short questionnaire pretraining and posttraining
      program. Attitudes toward ECT did not substantially differ between the 2 groups.
      For the entire sample, only 8.5% reported that they were well informed about ECT
      before the training session. More favorable attitudes were reported upon
      completion of the ECT education program compared with attitudes reported before
      training. These findings suggest that attitudes toward ECT increase favorably
      when individuals are provided with training and experience.

PMID- 17548977
TI  - A questionnaire survey of ECT practice in Australia.
AB  - OBJECTIVE: To determine the characteristics of electroconvulsive therapy (ECT)
      practice in Australia. METHOD: From October 1, 2002 to February 29, 2004, a 29
      item questionnaire was sent to 136 hospitals in Australia. RESULTS AND
      CONCLUSIONS: One hundred thirteen hospitals (83%) completed the questionnaire.
      Electroconvulsive therapy was available in 90 hospitals. A total of 7469 patients
      received 58,499 ECTs from 356 psychiatrists, which gives an average course length
      of 8.5 treatments. Electroconvulsive therapy use as assessed by the crude treated
      person rate was 37.85 persons per 100,000 population per annum. Of the number of
      patients, 63.4% were women. Brief-pulse devices were used in all hospitals.
      Electroencephalogram monitoring was used routinely in 80 hospitals. Of the total
      number of ECT treatments, 82.3% were given to patients with major depression,
      9.6% to patients with schizophrenia, 4.9% to patients with mania, and 1.7% to
      patients with catatonia. Patients who received ECT were in an age group older
      than 65 years (38.4%), followed by 45 to 64 years (28.3%), 25 to 44 years
      (26.3%), 18 to 24 years (6.9%), and less than 18 years (0.2%). Unmodified ECT was
      not used in any hospital. One thousand one hundred ninety-six patients received
      continuation ECT in 83 hospitals, and 1044 received maintenance ECT in 77
      hospitals. There was no case of ECT-related death during a survey period. Only 31
      hospitals rated their teaching program for medical students as acceptable to
      excellent, and for psychiatry residents, it was 58.

PMID- 17548978
TI  - Electroconvulsive therapy for comorbid major depressive disorder and
      posttraumatic stress disorder.
AB  - OBJECTIVE: Posttraumatic stress disorder (PTSD) and major depressive disorder
      frequently co-occur. Electroconvulsive therapy (ECT) is the most effective
      treatment for refractory major depressive disorder. We examined the effect of ECT
      in patients with co-occurring major depression and PTSD. METHOD: Using a
      retrospective chart review, we examined the outcome of the cases of 26 patients
      with major depression and co-occurring PTSD who received a course of ECT. The
      patients received either suprathreshold right unilateral, bilateral, or a
      combination of both. Using paired t test analysis, we compared the pretreatment
      and the posttreatment symptoms using the Montgomery-Asberg Depression Rating
      Scale and the PTSD Checklist. RESULTS: The patients receiving ECT had a
      significant reduction in the symptoms of major depression and some amelioration
      in PTSD symptoms. CONCLUSIONS: Electroconvulsive therapy may be an effective
      treatment for patients with refractory depression and co-occurring PTSD.

PMID- 17548979
TI  - Neuropathologic examination after 91 ECT treatments in a 92-year-old woman with
      late-onset depression.
AB  - Whereas pathological seizure states, such as temporal lobe epilepsy, are commonly
      associated with cell loss and glial scarring in the hippocampus, seizures induced
      via electroconvulsive therapy (ECT) have not been associated with histological
      evidence of neuronal damage. We present a case report including the late-life
      medical history and postmortem histology of an elderly woman with major
      depression who received 91 sessions of ECT during the last 22 years of her life.
      Given the large number of ECT sessions, and her advanced age, this case provides
      a strong test of whether ECT causes detectable evidence of neuronal damage. We
      examined the gross morphology of the hippocampus, hippocampal cytoarchitecture,
      and measures of neuropathology. We found no pathological changes that could be
      attributed to ECT. Only expected, age-related features were present. Corpora
      amylacea and rare neurofibrillary tangles were evident, but we failed to detect
      any obvious evidence of cell loss or gliosis. Cognition in this patient was
      intact as indicated by a perfect score on a Mini-Mental Status Examination
      administered 6 days before death at the age of 92. This case adds to the
      considerable evidence for the safety of ECT.

PMID- 17548980
TI  - Transient improvement of essential tremor during electroconvulsive therapy.
AB  - We present a patient who demonstrated transient yet significant improvement of
      essential tremor (ET) during electroconvulsive therapy. To our knowledge, this is
      the first such report. The improvement lasted during the course of
      electroconvulsive therapy and was of a similar magnitude to that which she had
      experienced on a first-line medication for ET. We discuss the potential
      pathophysiological implications of this observation in light of recent
      histopathologic findings in patients with ET.

PMID- 17548981
TI  - Resolution of catatonia by successful seizure induction via electroconvulsive
      therapy with electrodes applied bilaterally to the parietotemporal region.
AB  - Electroconvulsive therapy (ECT) has been shown to be effective in cases of
      medically intractable mood disorder and schizophrenia. However, some patients
      receiving ECT have only a short electroencephalographic seizure or no seizure at
      the maximum stimulus intensity and thus fail to obtain a therapeutic effect. A
      new treatment option is needed to induce therapeutic seizures in such patients.
      We report a case of catatonic schizophrenia that was resolved by successful
      seizure induction by means of ECT with electrodes applied bilaterally to the
      parietotemporal region after bifrontotemporal ECT failed to induce adequate
      seizure. We note that parietotemporal ECT can induce therapeutic seizures in
      patients with a high seizure threshold because more current penetrates the brain
      due to a decrease in shunted current.

PMID- 17548982
TI  - Safety of repeated courses of electroconvulsive therapy in a patient with
      Harrington rods.
AB  - BACKGROUND: Although modified electroconvulsive therapy (ECT) may rarely result
      in musculoskeletal complications, it has also been safely administered to
      patients with orthopedic morbidity. There is no literature on the safety of
      repeated courses of ECT in patients with Harrington rod implants. CASE REPORT: We
      describe a 30-year-old asthenic bipolar woman who, in 1997, had a Harrington
      compression assembly stabilizer fitted for spinal tuberculosis and who, between
      2000 and 2004, received 3 courses of modified ECT with a total of 28 treatments.
      In October 2006, she experienced her index episode of mania and was treated with
      7 ECTs that were modified with propofol (60 mg) and succinylcholine (0.83 mg/kg).
      Each ECT seizure was characterized by mild tonic-clonic movements that lasted 20
      to 40 seconds. Her mania remitted uneventfully with ECT. Radiological assessment
      after the ECT course showed that there were no orthopedic complications.
      DISCUSSION: Although our patient experienced no musculoskeletal complication
      despite the incomplete muscle relaxation, for maximum safety, we strongly
      recommend full muscle relaxation for all patients with orthopedic conditions who
      are treated with ECT. We also suggest that in such patients, short stimulus
      durations be used (to the extent possible) to minimize the duration of the tonic
      muscular contraction that occurs during the passage of the ECT stimulus. With
      these precautions, the orthopedic risks associated with well-modified ECT may be
      no greater or less than those associated with a fit of sneezing or coughing. Our
      report adds to the literature on the safety of modified ECT in patients with
      orthopedic conditions, such as those with Harrington rods in situ.

PMID- 17548983
TI  - Patients who inappropriately demand electroconvulsive therapy.
AB  - It is the authors' experience in our large, tertiary care electroconvulsive
      therapy (ECT) practice that some patients seem to demand continued ECT treatment,
      although the opinion of their clinicians is that ECT has not been beneficial. In
      this paper, through representative case examples, we outline some of the reasons
      why such patients request ECT and some of the reasons for their reported benefit
      other than true clinical improvement. We argue that some ECT patients are
      primarily motivated by the primary or secondary gain of being medical patients
      and that this needs to be considered by the clinician so as not to administer the
      treatments unnecessarily.

PMID- 17548985
TI  - Anticonvulsants during electroconvulsive therapy: review and recommendations.
AB  - OBJECTIVES: To review the literature on the concurrent use of electroconvulsive
      therapy (ECT) and anticonvulsant drugs (AC) and to provide recommendations to
      guide clinical practice. METHODS: A MEDLINE search (1985-2006) was performed,
      using the terms "electroconvulsive therapy," "anticonvulsants," "epilepsy,"
      "carbamazepine," "gabapentin," "lamotrigine," "topiramate," and "valproate,"
      supplemented by manual searches of guidelines and textbooks on ECT. RESULTS: To
      date, no prospective, randomized and controlled trials examining outcome and
      safety of the AC-ECT combination have been published. Existing data are from case
      reports on the use of ECT for psychiatric conditions that are simultaneously
      treated with AC, and from case reports of patients treated with ECT and AC for
      epilepsy or for psychiatric conditions with comorbid epilepsy. Apart from an
      occasional difficulty in eliciting seizures, no severe adverse effects or
      complications are reported. CONCLUSIONS: The literature that is currently
      available indicates that ECT can be safely and effectively administered to
      patients treated with various AC. There is, however, no evidence to combine the 2
      treatment modalities to augment therapeutic efficacy.

PMID- 17548984
TI  - Introduction of vagus nerve stimulation into a maintenance electroconvulsive
      therapy regimen: a case study and cost analysis.
AB  - OBJECTIVE: This case report describes the outcome of a patient implanted with the
      vagus nerve stimulation (VNS) device while receiving maintenance
      electroconvulsive treatment (M-ECT) and compares the costs of treatment options
      for treatment-resistant depression. METHODS: The patient, a male, aged 47 years
      with bipolar I disorder, treatment-resistant depression, and a 13-year history of
      depressions, was receiving M-ECT at 2-week intervals as well as antidepressant
      medications when he was implanted with the VNS device. His depression was
      assessed with the Montgomery-Asberg Depression Rating Scale. The cost analysis of
      treatment modalities placed M-ECT at $800 to $1000 per treatment and VNS at
      approximately $3900 annually (surgery, device, and office visits, approximately
      $31,300, was prorated over 8 years). RESULTS: Antidepressants and other
      medications were used in combination and were gradually changed while the patient
      was receiving electroconvulsive therapy. The patient improved with VNS and was
      able to discontinue M-ECT. His Montgomery-Asberg Depression Rating Scale scores
      had fluctuated between 2 and 56, but, after VNS, the scores decreased to a level
      consistent with remission and have remained at those levels. The patient reported
      feeling as well as he had felt at any time he could remember, began an exercise
      program, and lost 30 lbs. During the 10 months before implantation, 14
      electroconvulsive therapy treatments cost $11,200 to $14,000. For 10 months after
      implantation, 7 M-ECT treatments ($5600-$7000) plus prorated VNS ($3250) equaled
      $8850 to $10,250, $2350 to $3750 less than before implantation. CONCLUSIONS: This
      patient improved with VNS and was able to discontinue M-ECT. Introducing VNS
      effected a cost savings over M-ECT.

PMID- 17548986
TI  - Changes in electroconvulsive therapy service availability: think globally--act
      locally.

PMID- 17548987
TI  - Electroconvulsive therapy and arachnoid cysts.

PMID- 17548989
TI  - Inflammatory dural masses: if it's not one thing, it's another.

PMID- 17548990
TI  - Lymphoplasmacyte-rich meningioma mimicking idiopathic hypertrophic
      pachymeningitis.
AB  - A 24-year-old man presented with long-term headache and progressive visual loss.
      Neuro-ophthalmic manifestations included finger counting acuity in both eyes,
      weakly reactive pupils, pale optic discs, and increased deep tendon reflexes.
      Brain MRI showed meningeal thickening that involved the optic nerves and chiasm
      and enveloped and displaced the brainstem as far caudally as the foramen magnum.
      The diffuse extensive nature of the lesion suggested an inflammatory process such
      as idiopathic hypertrophic pachymeningitis (IHP), but anterior temporal brain
      biopsy disclosed a relatively high proportion of meningothelial cells with
      islands of polyclonal inflammatory reaction consistent with a diagnosis of
      lymphoplasmacyte-rich meningioma (LRM), a rare variant. Among the 19 reported
      cases of LRM, none has shown as extensive a mass as seen in our patient.
      Distinguishing between LRM and IHP is important because these entities are
      treated differently.

PMID- 17548991
TI  - Idiopathic hypertrophic pachymeningitis mimicking lymphoplasmacyte-rich
      meningioma.
AB  - A 28-year-old woman with a 6-year history of optic neuropathy and 8 years of
      hearing loss had enhancing dural lesions around the brain stem and in both
      internal auditory canals on MRI. Histopathology from cranial procedures performed
      in 1990 and 1993 was originally interpreted as inflammatory meningioma, now known
      as lymphoplasmacyte-rich meningioma (LRM). Because the clinical course was more
      consistent with a relapsing process, the original surgical specimens were
      restudied with additional immunocytochemical stains. The review led to a
      pathologic diagnosis of idiopathic hypertrophic pachymeningitis (IHP). IHP and
      LRM can be confused on both imaging and histopathologic grounds.

PMID- 17548992
TI  - Ophthalmoplegia, proptosis, and lid retraction caused by cranial nerve
      hypertrophy in chronic inflammatory demyelinating polyradiculoneuropathy.
AB  - A 53-year-old woman with long-standing chronic inflammatory demyelinating
      polyradiculoneuropathy (CIDP) developed progressive proptosis, lid retraction,
      and ophthalmoplegia. MRI showed enlarged, enhancing cranial nerves that initially
      gave rise to diagnostic confusion with Graves disease or orbitocavernous mass
      lesions. This report further documents that CIDP may cause hypertrophy of ocular
      motor and trigeminal nerves with imaging features that suggest alternative
      causes.

PMID- 17548993
TI  - Clinical without histopathological manifestations of inflammation in a patient
      with primary intraorbital optic nerve sheath meningioma.
AB  - A 28-year-old man with a biopsy-proven benign intraorbital optic nerve sheath
      meningioma developed recurrent clinical manifestations of ipsilateral retrobulbar
      inflammation 9 years after undergoing postoperative radiation therapy. Debulking
      of the tumor 11 years after the original surgery again revealed no pathologic
      signs of inflammation. Whether growth of tumor, surgery, radiation, or edema
      triggered the inflammatory manifestations is unclear. Our case affirms that
      primary optic nerve meningiomas may rarely cause episodic manifestations
      resembling those of idiopathic orbital inflammation that resolve with
      corticosteroid treatment.

PMID- 17548994
TI  - Retinal image stability in head tremor and nystagmus: counterintuitive
      observations.
AB  - BACKGROUND: Ophthalmoscopy of the fundus in a patient with head tremor is
      facilitated by image stability, whereas such observation of a patient with
      nystagmus is made difficult by image movement. Why does this occur? METHODS: We
      offer an explanation of these observations and derive mathematical proofs for
      both direct and indirect ophthalmoscopes in various states of ametropia. RESULTS:
      By means of image displacement calculations, we have created a graphical display
      of refractive error versus image displacement, showing zero displacement in
      emmetropia in head tremor and exaggerated displacement during nystagmus,
      regardless of the refractive status of the eye. CONCLUSIONS: Simple optics and a
      mathematical proof explain the clinical observations. The image stability in the
      patient with head tremor and the image instability in an eye with nystagmus are
      the consequences of the optical system of the eye.

PMID- 17548995
TI  - Palinopsia from posterior visual pathway lesions without visual field defects.
AB  - Palinopsia, or perseveration of a previously viewed image, may be caused by drug
      use or by posterior visual pathway lesions. Most cases of palinopsia due to
      visual pathway lesions have an associated homonymous hemianopic visual field
      defect. We report two patients with palinopsia caused by structural lesions of
      the posterior visual pathway in the absence of visual field defects. Patients
      with palinopsia should undergo neuroimaging even in the presence of normal visual
      fields.

PMID- 17548996
TI  - Spasmus nutans-like nystagmus is often associated with underlying ocular,
      intracranial, or systemic abnormalities.
AB  - BACKGROUND: There is uncertainty as to whether spasmus nutans (SN) is an isolated
      idiopathic entity or whether there are underlying conditions that could cause or
      be associated with the nystagmus. We undertook this study to determine the
      frequency of ocular, intracranial, and systemic conditions in patients with
      nystagmus having characteristics of SN. METHODS: We performed a chart review of
      22 consecutive patients examined from 2000 through 2005 at the Dean McGee Eye
      Institute and Children' Hospital of Oklahoma with nystagmus consistent with SN.
      We collected information related to gender, age at presentation and age at final
      visit, visual acuity, refractive error, laterality of nystagmus, presence of head
      nodding and torticollis, pattern of strabismus, neuroimaging and
      electroretinography results, and other associated clinical findings. RESULTS:
      Visual acuity was reduced in 75% of eyes at presentation and 58% of eyes at last
      visit. Eight patients had significant refractive error. Seven patients had
      strabismus. Two patients had chiasmal gliomas. Four patients had cone or rod/cone
      dystrophy. Only three patients had no associated ocular, intracranial, or
      systemic conditions. CONCLUSIONS: A substantial proportion of patients presenting
      with SN-like nystagmus have important underlying ocular, intracranial, or
      systemic abnormalities that may require evaluation and management.

PMID- 17548997
TI  - Lyme disease associated with postganglionic Horner syndrome and Raeder
      paratrigeminal neuralgia.
AB  - A 55-year-old woman developed severe unilateral headaches, periocular numbness,
      and Horner syndrome after presenting with symptoms consistent with Lyme disease.
      The combination of Horner syndrome and periocular headache and numbness
      constituted a diagnosis of Raeder paratrigeminal neuralgia. Although the
      headaches resolved with antibiotic treatment, the Horner syndrome persisted for
      at least 1 year. This case expands the spectrum of neurologic manifestations of
      Lyme disease to include postganglionic Horner syndrome as well as Raeder
      paratrigeminal neuralgia.

PMID- 17548998
TI  - Isolated bilateral internuclear ophthalmoplegia after ischemic stroke.
AB  - A 63-year-old man suddenly developed an isolated bilateral internuclear
      ophthalmoplegia (INO). High-resolution brain MRI showed signal abnormalities
      consistent with acute ischemic stroke limited to the infra-aqueductal region of
      the midbrain bilaterally. This case offers graphic evidence that stroke can be
      responsible for an isolated bilateral INO.

PMID- 17548999
TI  - Isolated sixth cranial nerve aplasia visualized with Fast Imaging Employing
      Steady-State Acquisition (FIESTA) MRI.
AB  - An otherwise healthy 12-month-old girl presented for evaluation of reduced
      abduction of the left eye detected at 6 months of age. The remainder of the
      examination was unremarkable. A special MRI sequence-fast imaging employing
      steady-state acquisition (FIESTA)-visualized the right but not the left sixth
      nerve cisternal segment. This is the first reported use of the MRI FIESTA
      sequence to diagnose aplasia of the sixth cranial nerve.

PMID- 17549000
TI  - Imaging nuances of perineural spread of head and neck malignancies.
AB  - Perineural spread is a common growth pattern of head and neck malignancies.
      Recognizing this pattern by imaging is important for two reasons: 1) it may be
      the only evidence of malignancy; and 2) its presence in conjunction with a mass
      converts management from surgical resection to radiation or chemotherapy. High
      field strength magnets and thin sections with high resolution and fat suppression
      now allow earlier diagnosis of this entity, but even with these imaging
      developments, familiarity with the relevant anatomy and the subtle alterations on
      MRI are necessary to identify this condition.

PMID- 17549001
TI  - The near response: the contributions of Kenji Ohtsuka, MD.
AB  - Kenji Ohtsuka, MD and his colleagues at the Sapporo Medical University have
      investigated the central organization of the near response with anatomical and
      neurophysiologic studies in cats. Based on their data and clinical observations,
      they proposed that the rostral pole of the superior colliculus has a critical
      role in the control of accommodation, vergence, and fixation. Although the
      central pathways have yet to be fully worked out, the contributions of Dr.
      Ohtsuka, who died in 2005, have laid an important foundation in the understanding
      of these functions.

PMID- 17549002
TI  - Radiation retinopathy after fractionated stereotactic conformal radiotherapy for
      primary intraorbital optic nerve sheath meningioma.

PMID- 17549003
TI  - Ophthalmoplegia and lid retraction with normal initial orbit CT imaging in
      extraocular muscle metastases as the presenting sign of breast carcinoma.

PMID- 17549004
TI  - The 2007 International Stroke Conference San Francisco, California February 7-9,
      2007.

PMID- 17549006
TI  - RNA in brain disease: no longer just "the messenger in the middle".
AB  - RNA research has made great progress in recent years. A variety of unforeseen
      complexities have been identified, many with relevance to human brain disease.
      For example, neurologic illnesses may arise because of perturbations in distinct
      but interrelated tiers of RNA-based genetic regulation: pre-mRNA splicing;
      nonsplicing RNA modifications; and mRNA translational regulation. Furthermore,
      there is poor correlation between mRNA levels and protein levels in mammalian
      cells, due partly to complicated post-transcriptional regulation by hitherto
      unknown noncoding RNAs. Some noncoding RNAs have been shown to be involved in
      human brain diseases. Diseases potentially mediated by alterations in RNA
      processes include tauopathies, myotonic dystrophy, Alzheimer disease, brain
      cancer, and many others. Here we present an overview of new research highlighting
      functions for RNA that far surpass the "messenger in the middle" role and that
      identify RNA molecules as important agents in the human brain in health and in
      disease states.

PMID- 17549007
TI  - Hematopoietic prostaglandin D synthase and DP1 receptor are selectively
      upregulated in microglia and astrocytes within senile plaques from human patients
      and in a mouse model of Alzheimer disease.
AB  - Prostaglandin (PG) D2 is produced in activated microglia by the action of
      hematopoietic PGD synthase (HPGDS) and plays important roles in
      neuroinflammation. Because the fact that neuroinflammation accelerates
      progression of Alzheimer disease (AD) has been documented, we investigated
      whether PGD2 is also involved in the pathology of AD. Here, we report that the
      level of the mRNA of the receptor for PGD2 (DP1) was increased in AD brains
      compared with the level in non-AD brains. Immunocytochemical analysis showed
      HPGDS expression to be localized in the microglia surrounding senile plaques. In
      situ hybridization studies revealed that DP1 mRNA was specifically localized in
      microglia and reactive astrocytes within senile plaques of AD brains. In the
      brain of Tg2576 mice, a model of AD, HPGDS and DP1 proteins were mainly localized
      immunocytochemically in microglia and astrocytes in the plaques, and the levels
      of their mRNAs increased in parallel with amyloid beta deposition. These results
      indicate that PGD2 may act as a mediator of plaque-associated inflammation in AD
      brain and may explain the pharmacologic mechanisms underlying the favorable
      response of patients with AD to nonsteroidal anti-inflammatory drugs.

PMID- 17549008
TI  - Bilateral changes after neonatal ischemia in the P7 rat brain.
AB  - Neurogenesis persists throughout life in the rodent subventricular zone (SVZ) and
      subgranular zone (SGZ) and increases in the adult after brain injury. In this
      study, postnatal day 7 rats underwent middle cerebral artery electrocoagulation
      and transient homolateral common carotid artery occlusion, a lesioning protocol
      that resulted in ipsilateral (IL) forebrain ischemic injury, leading to a
      cortical cavity 3 weeks later. The effects of neonatal ischemia on hemispheric
      damage, cell death, cell proliferation, and neurogenesis were examined 4 hours to
      6 weeks later by the terminal deoxynucleotidyl transferase dUTP nick-end labeling
      assay and immunohistochemistry of Ki-67 in proliferating cells and of
      doublecortin, a microtubule-associated protein expressed only by immature
      neurons. Neonatal ischemic injury resulted in persistent reduced IL and transient
      reduced contralateral (CL) hemispheric areas, a consequence of sustained and
      transient cell death in the IL and CL areas, respectively. Ki-67 immunostaining
      revealed 3 peaks of newly generated cells in the dorsal SVZ and SGZ in the IL
      side and also in the CL side at 48 hours and 7 and 28 days after ischemia. Double
      immunofluorescence revealed that most of the Ki-67-positive cells were astrocytes
      at 48 hours. Ischemic injury also stimulated SVZ neurogenesis, based on increased
      doublecortin immunostaining in both SVZs at 7 to 14 days after injury.
      Doublecortin-positive neurons remained visible around the lesion at 21 days but
      displayed an immature shape in discrete chains or clusters. Although unilateral
      ischemic damage was produced, results indicate successful regenerative changes in
      the CL hemisphere, allowing anatomical recovery.

PMID- 17549009
TI  - Cytomegalic interneurons: a new abnormal cell type in severe pediatric cortical
      dysplasia.
AB  - A defining histopathologic feature of Taylor-type cortical dysplasia (CD) is the
      presence of cytomegalic neurons and balloon cells. Most cytomegalic neurons
      appear to be pyramidal-shaped and glutamatergic. The present study demonstrates
      the presence of cytomegalic GABAergic interneurons in a subset of pediatric
      patients with severe CD. Cortical tissue samples from children with mild, severe,
      and non-CD pathologies were examined using morphologic and electrophysiologic
      techniques. By using in vitro slices, cytomegalic cells with characteristics
      consistent with interneurons were found in 6 of 10 patients with severe CD.
      Biocytin labeling demonstrated that cytomegalic interneurons had more dendrites
      than normal-appearing interneurons. Whole-cell patch clamp recordings showed that
      cytomegalic interneurons had increased membrane capacitance and time constant
      compared with normal-appearing interneurons. They also displayed signs of
      cellular hyperexcitability, evidenced by increased firing rates, decreased action
      potential inactivation, and the occurrence of spontaneous membrane
      depolarizations. Single-cell reverse transcription-polymerase chain reaction and
      immunohistochemistry for GABAergic markers provided further evidence that these
      cells were probably cytomegalic interneurons. The pathophysiologic significance
      of GABAergic cytomegalic interneurons in severe CD tissue is unknown, but they
      could inhibit glutamatergic cytomegalic pyramidal neurons, or contribute to the
      synchronization of neuronal networks and the propagation of ictal activity in a
      subset of pediatric patients with severe CD.

PMID- 17549010
TI  - Identification of novel biomarkers in pediatric primitive neuroectodermal tumors
      and ependymomas by proteome-wide analysis.
AB  - The aim of this study was to identify aberrantly expressed proteins in pediatric
      primitive neuroectodermal tumors (PNETs) and ependymomas. Tumor tissue of 29 PNET
      and 12 ependymoma patients was subjected to 2-dimensional difference gel
      electrophoresis. Gel analysis resulted in 79 protein spots being differentially
      expressed between PNETs and ependymomas (p < 0.01, fold change difference in
      expression >2). Three proteins, stathmin, annexin A1, and calcyphosine, were
      chosen for validation by immunohistochemistry. Stathmin was expressed 2.6-fold
      higher in PNETs than in ependymomas, and annexin A1 and calcyphosine were
      expressed 2.5- and 37.6-fold higher, respectively, in ependymomas. All PNETs
      showed strong staining for stathmin, and all ependymomas were strongly positive
      for annexin A1, whereas control tissues were negative. Calcyphosine
      immunoreactivity was observed in 59% of the ependymomas and was most profound in
      ependymoma tissue showing epithelial differentiation. mRNA expression levels of
      stathmin, annexin A1, and calcyphosine significantly correlated (Rs = 0.65 [p <
      0.0001], Rs = 0.50 [p = 0.001], and Rs = 0.72 [p < 0.0001], respectively) with
      protein expression levels. In conclusion, using a proteome-wide approach,
      stathmin, annexin A1, and calcyphosine were successfully identified as tumor
      specific proteins in pediatric PNETs and ependymomas. Ongoing studies are focused
      on characterizing the role of these proteins as tumor markers and potential drug
      targets in pediatric brain tumors.

PMID- 17549011
TI  - Motor neuron disease in transgenic mice with an H46R mutant SOD1 gene.
AB  - Human familial amyotrophic lateral sclerosis with an H46R mutant Cu/Zn superoxide
      dismutase (SOD1) gene is characterized by initial muscle weakness and atrophy in
      the legs and a very long-term clinical course (approximately 15 years).
      Transgenic mice with this mutation generated in our laboratory occasionally
      showed aggregates in the anterior horns and axonal degeneration in all white
      matter sections of the spinal cord on plastic sections at the presymptomatic
      stages (12 and 16 weeks old), although conventional staining revealed no
      pathologic changes. At the symptomatic stages (20 and 24 weeks), loss of anterior
      horn neurons was observed. On plastic sections, aggregates were frequently seen
      not only in the anterior horns but also in the posterior horns and in all
      sections of white matter. Degenerated fibers were observed in the anterior and
      posterior roots as well as in white matter. Electron and immunoelectron
      microscopic observation revealed human SOD1- and ubiquitin-positive aggregates
      consisting of intermediate filaments in the anterior horn even from an early
      presymptomatic stage. Thus, H46R mutant SOD1 transgenic mice are characterized by
      widespread pathologic changes of the spinal cord that extend beyond the motor
      system, including many aggregates lacking vacuoles. The close pathologic
      similarity makes this animal model suitable for the investigation of human
      familial amyotrophic lateral sclerosis with the mutation.

PMID- 17549012
TI  - Autophagocytosis of mitochondria is prominent in Alzheimer disease.
AB  - Mitochondrial abnormalities are prominent in Alzheimer disease. In this study, 2
      mitochondrial markers, cytochrome oxidase-1 and lipoic acid, a sulfur-containing
      cofactor required for the activity of several mitochondrial enzyme complexes,
      were compared using light and electron microscopic analyses and immunoblot
      assays. Both lipoic acid and cytochrome oxidase-1 immunoreactivity are increased
      in the cytoplasm of pyramidal neurons in Alzheimer disease compared with control
      cases. Of significance, lipoic acid was found to be strongly associated with
      granular structures, and ultrastructure analysis showed localization to
      mitochondria, cytosol, and, importantly, in organelles identified as autophagic
      vacuoles and lipofuscin in Alzheimer disease but not control cases. Cytochrome
      oxidase-1 immunoreactivity was limited to mitochondria and cytosol in both
      Alzheimer and control cases. These data suggest that mitochondria are key targets
      of increased autophagic degradation in Alzheimer disease. Whether increased
      autophagocytosis is a consequence of an increased turnover of mitochondria or
      whether the mitochondria in Alzheimer disease are more susceptible to autophagy
      remains to be resolved.

PMID- 17549014
TI  - Panel review of anaplastic oligodendroglioma from European Organization For
      Research and Treatment of Cancer Trial 26951: assessment of consensus in
      diagnosis, influence of 1p/19q loss, and correlations with outcome.
AB  - The diagnosis of anaplastic oligodendroglioma (AOD) or anaplastic
      oligoastrocytoma (AOA) is subject to interobserver variation. The aim of this
      study was to estimate consensus in typing and grading of these tumors using tumor
      material collected in a large prospective randomized phase III study and to
      correlate the consensus diagnosis with the 1p/19q status of the tumors and the
      clinical outcome. The available pathology material of the first 150 patients,
      randomized into the European Organization for Research and Treatment of Cancer
      Trial 26951, was reviewed by an independent panel of 9 neuropathologists. The
      presence of deletions of 1p and 19q was assessed by fluorescence in situ
      hybridization with locus-specific probes. The panel reached consensus on the
      diagnosis of AOD in 52% of the tumors that had been diagnosed as AOD by the local
      pathologists, whereas only 8% of the local diagnosis of AOA was confirmed with
      consensus. The concordance on the panel diagnosis of AOD was high (intraclass
      correlation = 86%). The survival curves for AOD with 1p/19q loss, AOD without
      these losses, and AOA without 1p/19q loss ran separately in this order. The
      absence of necrosis and the presence of endothelial abnormalities were correlated
      with better outcomes. In multivariate analysis, patients' age, 1p/19q loss, and
      necrosis were identified as independent prognostic factors.

PMID- 17549013
TI  - Neuroprotective interventions targeting detrimental host immune responses protect
      mice from fatal alphavirus encephalitis.
AB  - Systemic treatment with the tetracycline derivative, minocycline, attenuates
      neurologic deficits in animal models of amyotrophic lateral sclerosis, hypoxic
      ischemic brain injury, and multiple sclerosis. Inhibition of microglial
      activation within the CNS is 1 mechanism proposed to underlie the beneficial
      effects of the drug in these systems. Given the widening scope of acute viral
      encephalitis caused by mosquito-borne pathogens, we investigated the therapeutic
      effects of minocycline in a murine model of fatal alphavirus encephalomyelitis in
      which widespread microglial activation is known to occur. We found that
      minocycline conferred significant protection against both paralysis and death,
      even when started after viral challenge and despite having no effect on CNS virus
      replication or spread. Further studies demonstrated that minocycline inhibited
      early virus-induced microglial activation and that diminished CNS production of
      the inflammatory mediator, interleukin (IL)-1beta, contributed to its protective
      effect. Therapeutic blockade of IL-1 receptors also conferred significant
      protection in our model, validating the importance of the IL-1 pathway in disease
      pathogenesis. We propose that interventions targeting detrimental host immune
      responses arising from activated microglia may be of benefit in humans with acute
      viral encephalitis caused by related mosquito-borne pathogens. Such treatments
      could conceivably act through neuroprotective rather than antiviral mechanisms to
      generate these clinical effects.

PMID- 17549015
TI  - Dual role of intrauterine immune challenge on neonatal and adult brain
      vulnerability to hypoxia-ischemia.
AB  - Epidemiologic evidence has underlined the impact of prenatal inflammation on the
      development of postnatal hypoxia-ischemia (HI) brain injury. To study to what
      extent prenatal inflammation affects CNS vulnerability later during development,
      C57BL/6 mice were subjected to intrauterine injection of lipopolysaccharide (LPS)
      at gestational day 15. At postnatal day (PND) 5, 9, and 70, the offspring were
      subjected to HI. It was found that, in neonatal mice, LPS-exposed brains showed
      markedly enhanced brain injury after HI, whereas in adult mice, LPS exposure
      resulted in a significant reduction in tissue loss after HI. Reduced myelin in
      subcortical white matter was noticed after HI in the LPS-exposed brains at PND14
      and PND75. Increased activities of nuclear factor-kappaB and caspase-3 were
      obtained in fetal/neonatal brain after LPS administration. Conclusions were that
      1) a prenatal low dose of LPS sensitized to HI-induced brain injury in neonates
      but confers protection in adulthood, 2) reduced myelination is seen after
      prenatal LPS exposure and HI in both neonatal and adult mice despite the fact
      that LPS reduced total tissue loss in adult mice; and 3) nuclear factor-kappaB
      and caspase-3 activation early after LPS exposure may play a role in the
      sensitization/protection (preconditioning) effects.

PMID- 17549016
TI  - Learning from armed conflicts.

PMID- 17549017
TI  - Civilian and detainee orthopaedic surgical care at an Air Force theater hospital.
AB  - This study is a retrospective analysis of the orthopaedic care rendered to Iraqi
      citizens, both military and civilian, and detainees in Balad, Iraq, at an Air
      Force theater hospital. Defining the scope of care for this patient group and
      emphasizing the differences in care provided for the endemic population in
      contrast to the rapidly air-evacuated Coalition injured combatant are the primary
      focus of the study. Approximately 50% of more than 1600 trauma/combat-related
      injury admissions to Air Force Theater Hospital in Balad, Iraq, from the period
      of September 2, 2005 through January 18, 2006, were Iraqi citizens and detainees.
      The care rendered to this population differed from the care given to a rapidly
      air-evacuated patient in that definitive care of all combat wounds, including
      fracture care and soft tissue management, was the responsibility of the deployed
      surgeons. Open reduction and internal fixation, definitive debridement, Wound VAC
      placement (Vacuum-Assisted Closure Device; KCI International, San Antonio, Tex),
      and final soft tissue management were performed at Air Force Theater Hospital.
      All patients were treated according to their injuries, including detainees, who
      received the same level of care as any other injured patient. This article will
      depict examples of the civilian and detainee orthopaedic care available and
      performed in a war zone and how that care differed from that rendered to a
      rapidly evacuated American combatant. Injured Coalition combatants received high
      level damage control orthopaedic care and initial debridements, with external
      fixation as the single most common means of long-bone fracture stabilization.
      Civilians and detainees seen at Balad received the same high-level care and much,
      if not all, of their definitive care while at Air Force Theater Hospital. The
      care rendered to Iraqi citizens and detainees at an Air Force theater hospital is
      described, with multiple case examples that reflect a high level of definitive
      care offered in a war zone.

PMID- 17549018
TI  - Avulsion injuries of the nail bed do not need nail bed graft.
AB  - From 1985 to 1992, 12 cases of severe avulsion injuries of the nail bed were
      treated by allowing the nail bed to regenerate naturally, without a nail bed
      graft irrespective of the extent of nail bed loss. This involved simply covering
      the residual nail bed with the nail splint for a period of approximately 6 weeks
      or until the nail bed was observed to be fully regenerated. The patients were
      then followed up until full nail growth. It was observed that the nail bed
      regenerated spontaneously, followed by a normal nail growth identical to the
      contralateral uninjured nail.Proper coverage of the nail bed protected the
      culture milieu conducive to natural nail bed regeneration, and nail bed grafting
      was not necessary irrespective of the extent of tissue loss.

PMID- 17549019
TI  - Transfer of the intercostal nerves to the nerve of the long head of the triceps
      to recover elbow extension in brachial plexus palsy.
AB  - Restoration of elbow flexion is the first goal in brachial plexus injuries. The
      current procedures using nerve grafts and nerve transfers authorize more
      extensive repairs, with different possible targets: shoulder, elbow extension,
      and hand. Elbow extension is important to stabilize the elbow without the
      contralateral hand and allows achieving a useful grasp. The transfer of the
      intercostal nerves to the nerve of the long head of the triceps may restore this
      function in brachial plexus palsies. Furthermore, in case of C5 to C7 palsy, this
      transfer spares the radial nerve and gives a chance to spontaneous triceps
      recovery by the reinnervation from C8 root. Moreover, in case of absence or
      insufficient (M0 to M2 according to Medical Research Council scoring) recovery of
      elbow flexion strength by nerve surgery, the reinnervated triceps can be
      transferred. We present the technique of intercostal nerve transfer to the long
      head of the triceps branch to restore elbow extension in brachial plexus palsy.
      Results concerning 10 patients are presented.

PMID- 17549020
TI  - Low-profile dorsal plating for dorsally angulated distal radius fractures.
AB  - Dorsal plating emerged as an effective treatment for dorsally displaced distal
      radius fractures in the late 1980s. In addition to some mechanical advantages,
      this method provided a clear view of the articular surface and the ability to
      restore the anatomy. However, because of the frequent occurrence of extensor
      tendon complications in the early designs of dorsal plates, the volar approach
      gained favor for repairing these types of fractures. Recent improvements in
      dorsal plating designs have yielded increasingly thinner, precontoured plates
      with rounded edges and low-profile flush screw heads. These new plates have shown
      decreased rates of extensor tendon complications while retaining the advantages
      of the original dorsal approach. The authors have used this technique in more
      than 70 cases during a 4-year period. This article will review the history,
      indications, contraindications, technique, and rehabilitation for dorsal plating
      of dorsally angulated distal radius fractures.

PMID- 17549021
TI  - Nonvascularized osteoarticular allograft replacement of the proximal
      interphalangeal joint after extensive loss of bone, joint, and extensor tendon.
AB  - Nonvascularized small-joint allografts are a potentially attractive alternative
      to prosthetic implantation in cases of posttraumatic destruction of the proximal
      interphalangeal joint combined with metaphyseal and diaphyseal metacarpal or
      phalangeal bone loss, as well as soft tissue tendon defects of the digital
      extensor mechanism. Benefits include the absence of donor site defect, the
      ability to simultaneously reconstruct deficiency of the extensor mechanism,
      restore digital length and phalangeal (and metacarpal) bone stock in the face of
      bone loss, and the provision of an osteoinductive platform onto which creeping
      substitution can occur. Difficulties include an increased potential for infection
      and the potential for narrowing of the joint space because of articular cartilage
      loss. Early results suggest that the benefit of this technique lies in its
      ability to restore bone stock and soft tissue integrity that would make later
      prosthetic joint replacement feasible.

PMID- 17549022
TI  - Endoscopic single-incision extensor indicis transposition for extensor pollicis
      longus reconstruction.
AB  - Traditional methods for harvesting the extensor indicis (EI) tendon for
      transposition to the extensor pollicis longus (EPL) tendon using direct
      visualization commonly require 3 incisions. The authors describe an endoscopic EI
      tendon transposition for EPL tendon reconstruction as an alternative technique
      for the traditional open technique. This new modification of endoscopic EI
      transposition to EPL has the benefit over the standard harvesting technique of
      only 1 incision to accomplish the complete procedure and results in less
      scarring. To date, the authors have only operated on ruptures after radius
      fractures without significant synovitis in the area of the extensor compartment.

PMID- 17549023
TI  - Flap advancement coverage after excision of large mucous cysts.
AB  - Mucous cysts are common problems seen by hand surgeons. Surgical excision of
      symptomatic cysts is the most commonly accepted treatment. Removal of large
      mucous cysts often requires simultaneous flap coverage or skin grafting for the
      resulting defect. We present the use of a dorsal advancement flap to permit
      excellent skin coverage after cyst excision with a tension-free closure.

PMID- 17549024
TI  - Antibiotic-impregnated cement spacer for bone defects of the forearm and hand.
AB  - Management of bone loss, particularly in the face of open or contaminated wounds,
      presents a reconstructive challenge. Polymethylmethacrylate impregnated with
      antibiotics has been used successfully in the treatment of infected total joint
      arthroplasty and open fractures. The cement delivers high-dose local
      concentrations of antibiotics while filling a space. This article presents our
      use of an antibiotic-impregnated cement spacer for bone loss in the forearm or
      hand in the face of open or infected wounds. The cement spacer fills a potential
      space, prevents the involution of the surrounding soft tissue, and delivers
      appropriate antibiotics. When the spacer is removed, the remaining sheath serves
      to hold and contain the cancellous bone graft.

PMID- 17549025
TI  - Treatment of early basal joint arthritis using a combined arthroscopic
      debridement and metacarpal osteotomy.
AB  - Osteoarthritis of the thumb basal joint is a common and disabling condition, and
      early stages of which are often seen in middle-aged women. Arthroscopic
      assessment of the first carpometacarpal joint allows easy identification and
      classification of joint pathology with minimal morbidity. This allows the
      condition to be managed either arthroscopically or converted to an open procedure
      as indicated. Different procedures have been described to treat different stages
      of this disease. The senior author has recently described an arthroscopic staging
      system to determine treatment for basal joint osteoarthritis. We now present our
      surgical technique and early clinical experience with arthroscopic synovectomy,
      debridement, and corrective osteotomy for arthroscopic stage II of thumb basal
      joint arthritis. Forty-three patients (38 women and 5 men) were arthroscopically
      diagnosed as having stage II basal joint osteoarthritis of the thumb between 1998
      and 2001, and they were the focus of the present study. In all the patients,
      there was no improvement after a period of 6 to 12 weeks of conservative
      treatment. All the procedures were performed by the senior author. The surgical
      procedure included arthroscopic synovectomy, debridement, and occasional thermal
      capsulorraphy, followed by an extension-abduction closing wedge osteotomy in all
      the cases. A 0.045-in Kirschner wire provided stability to the osteotomy. By
      performing an osteotomy that redirects the axial loads in this joint, we have
      obtained satisfactory results in terms of pain relief, stability, and pinch
      strength. Arthroscopy allows us to not only determine the optimum indication for
      this osteotomy, but also to debride the joint and minimize the inflammatory
      response. Hence, we recommend arthroscopic synovectomy, debridement with or
      without a thermal capsulorraphy, and a dorsoradial closing wedge osteotomy for
      the treatment of arthroscopic stage II of thumb carpometacarpal joint
      osteoarthritis.

PMID- 17549026
TI  - Treatment of pediatric supracondylar humerus fractures in the community hospital.
AB  - BACKGROUND: Supracondylar fractures of the humerus are among the most common
      elbow injuries in the pediatric population. Because of the significant morbidity
      associated with treating displaced pediatric supracondylar humerus fractures,
      most community-based orthopedic surgeons prefer to transfer these injuries to
      specialty children's hospitals. Our intention in writing this article was to
      document and evaluate the results we obtained using the lateral diverging pin
      technique to treat patients at our community hospital. In doing so, we set out to
      determine if our results were comparable to those of specialty hospitals,
      allowing us in the future to eliminate the inconvenience placed on patients and
      their families when being transferred to a specialty facility. METHODS: We
      retrospectively reviewed the patients treated surgically at our institution for a
      closed Gartland type II or type III supracondylar distal humerus fracture during
      the months of September and October of 2005. The medical records and radiographs
      of all children who had been treated for a displaced extension-type supracondylar
      humerus fractures were evaluated. The data recorded from the chart review
      included the age and sex of the patients, preoperative and postoperative
      neurovascular status, operative techniques (2 vs 3 lateral entry point Kirschner
      wires), and the operative time (start to close). The radiographs were reviewed to
      determine the Gartland type of fracture and the Baumann angle on the
      anteroposterior film immediately postoperative and at the time of fracture union.
      RESULTS: Four Gartland type II and 3 Gartland type III fractures were identified
      during the study period. There were 3 boys and 4 girls with a mean age of 6.29
      years (range, 3.92-8.58 years). The mean immediate postoperative Baumann angle
      was 18.29 degrees (range, 10-25 degrees). At the time of fracture union, the mean
      Baumann angle was 19.0 degrees (range, 14-22 degrees). The mean range-of-motion
      loss as compared with the extension loss (range, 10-2 degrees) and 4.57 degrees
      of flexion loss (range, 10-2 degrees). The mean operative time was 20.43 minutes
      (range, 7-37 minutes). CONCLUSIONS: Our results show the change in Baumann angle
      and loss of range of motion compare favorably with results of studies done at
      specialty hospitals. We believe that the divergent lateral pinning technique, in
      combination with postoperative splinting and a sling can provide excellent
      results while eliminating the risk of injury to the ulnar nerve. With this
      knowledge, we feel that the advantage to treating these fractures at a community
      hospital is the elimination of the anxiety, stress, and time spent waiting in the
      emergency department of multiple hospitals.

PMID- 17549027
TI  - Difference between the epicondylar and cylindrical axis of the knee.
AB  - Locating the true flexion-extension axis of the knee can play an important role
      in component placement in a total knee arthroplasty, especially using
      contemporary computer-assisted surgical navigation. We determined if the commonly
      used transepicondylar axis is an accurate and reproducible substitute for the
      flexion-extension axis. Twenty-three fresh-frozen cadaveric distal femurs with
      intact soft tissue were imaged with computed tomography and reconstructed in
      three-dimensional virtual space. The transepicondylar axis was compared with a
      line equidistant from the articular surface of each femoral condyle. Measures
      were performed by three observers three times for each specimen. Interobserver
      and intraobserver variations were small, but the differences between axes were
      approximately 5 degrees. The difference between axes decreased when projected
      from three-dimensional space to traditional two-dimensional planes (coronal and
      transverse), explaining why this discrepancy has not been previously documented.
      The greater difference in three-dimensional space may account for midrange
      instability reported in total knee arthroplasty. The increased accuracy afforded
      by computer-assisted surgical navigation in total knee arthroplasty may be lost
      and increased malposition of components may occur if this discrepancy between
      reference axes is not appreciated and addressed.

PMID- 17549028
TI  - Clinical experience with daptomycin treatment of foot or ankle osteomyelitis: a
      preliminary study.
AB  - We retrospectively reviewed 25 patients with foot or ankle osteomyelitis reported
      to a registry who were treated with daptomycin. The patients' clinical experience
      was analyzed and described at a median dose of 6 mg/kg (range, 4-6.2 mg/kg) and a
      median duration of 38 days (range, 6-59 days). Twenty-three patients received
      daptomycin as secondary or tertiary therapy, primarily for not responding to
      their prior antibiotic therapy (n = 15). Concomitant antibiotics were given to 11
      patients, mostly for Gram-negative and/or anaerobic coverage. Methicillin
      resistant Staphylococcus aureus was the most common pathogen overall (15 of 25
      patients). The median followup interval was 9 weeks (range, 0.5-77 weeks).
      Outcomes at the end of therapy were 16 patients' symptoms resolved, eight
      patients improved, and one patient did not respond to therapy; at followup, 19
      patients' symptoms resolved, three patients improved, and three patients did not
      respond to therapy. Ongoing antibiotics were given to 52% of patients for a
      minimum of 8 days (median, 30 days; range, 8-232 days). Four patients with an
      implant (all removed) were successfully treated. Daptomycin appears promising for
      foot and ankle osteomyelitis caused by Gram-positive bacteria. Prospective,
      controlled clinical trials of daptomycin for osteomyelitis are warranted.

PMID- 17549029
TI  - New emerging role of pitx1 transcription factor in osteoarthritis pathogenesis.
AB  - Osteoarthritis is the most common form of arthritis and the precise etiology of
      this disease remains unclear. We took a candidate gene-driven strategy approach
      based on the observation that Pitx1 transcription factor was found during hind
      limb development in regions giving rise to cartilage joints, long bones and
      skeletal muscles, while its partial in activation led to a progressive formation
      of osteoarthritis-like phenotype in aging Pitx1 +/- mice. To determine whether
      Pitx1 plays a role in osteoarthritis pathogenesis in humans, we performed an
      expression analysis of the pitx1 gene using RNA prepared from articular
      chondrocyte cultures derived from knee cartilage of patients with osteoarthritis
      and age- and gender-matched control subjects. Pitx1 expression was detected in
      articular chondrocytes derived from matched control subjects, whereas in
      osteoarthritic articular chondrocytes, Pitx1 expression was barely detectable by
      reverse transcription-polymerase chain reaction. Immunostaining with anti-Pitx1
      antibodies of histologic sections of human osteoarthritic and control cartilage
      showed Pitx1 proteins only in the cartilage of control subjects, whereas Pitx1
      proteins were hardly detected in human osteoarthritic sections. Collectively, our
      results uncovered an unrecognized role for Pitx1 in osteoarthritis and
      elucidation of the mechanism turning off its expression will clarify its
      pathophysiological relevance.

PMID- 17549030
TI  - Sucrose, xylitol, and erythritol increase PMMA permeability for depot
      antibiotics.
AB  - Release of antibiotics from antibiotic-loaded PMMA is dependent on its
      permeability. Loading PMMA with soluble particulate filler has been proposed to
      increase permeability and antibiotic release for beads and spacers. We therefore
      assessed particulate sucrose, xylitol, and erythritol as fillers to increase the
      permeability and elution kinetics of filler-loaded PMMA. Based on lower
      solubility, we hypothesized that erythritol would not enhance permeability and
      elution as much as xylitol and sucrose. We made filler-loaded PMMA beads with
      each of the three fillers combined with phenolphthalein, and soaked in 0.1% NaOH
      solution. Permeability was assessed qualitatively by relative depth of
      phenolphthalein color change caused by penetration of NaOH solution into
      subsequently split beads. Elution was quantitatively assessed by
      spectrophotometric light absorption measurements of the eluent. Fluid penetration
      reached the center of 7-mm beads by day 15, similar for all three materials.
      Elution of phenolphthalein was greater for xylitol than for the other two
      materials. Particulate sucrose, xylitol, and erythritol fillers increase PMMA
      permeability and elution kinetics but relative solubility did not determine the
      relative degree of enhancement of permeability and elution by these materials.

PMID- 17549031
TI  - Covalently attached vancomycin provides a nanoscale antibacterial surface.
AB  - Despite improved strategies for treating periprosthetic infection, current
      antibiotic delivery approaches are imperfect and can result in bacterial
      resistance and recalcitrant bio-films. To address the issues, we developed a
      covalently linked vancomycin-titanium implant interface that prevents and
      possibly eliminates bacterial colonization. We determined the amount of
      vancomycin immobilized on the titanium surface and assessed vancomycin stability
      and activity over time. When incubated with Staphylococcus aureus, the vancomycin
      titanium surface showed an almost complete absence of adherent bacteria. To
      determine if continual exposure to vancomycin-titanium would cause decreased
      susceptibility to the antibiotic, S. aureus was incubated with vancomycin
      titanium for 1 week or 4 weeks; these bacteria did not show an increased minimum
      inhibitory concentration for vancomycin. We tested the long-term stability of the
      vancomycin-titanium surface by incubation in phosphate-buffered saline for 11
      months and then challenging the surface with S. aureus. Fluorescent staining for
      bacteria indicated the vancomycin-titanium retained its bactericidal activity.
      Finally, osteoblasts seeded on the vancomycin-titanium surface exhibited no
      change in viability, indicating the surface supports bone cell adhesion. Based on
      these observations, covalent modification of the titanium surface with an
      antibiotic may be viewed as a potential new tool in preventing or eliminating
      periprosthetic infection.

PMID- 17549032
TI  - Elution behavior of daptomycin-loaded calcium sulfate pellets: a preliminary
      study.
AB  - Daptomycin is a new antibiotic active against many resistant Gram-positive
      organisms and seems an appropriate candidate for local delivery for severe
      musculoskeletal infections. Calcium sulfate dihydrate as a delivery vehicle is
      readily resorbable, allows new bone formation, and can be combined with
      therapeutic agents. We compared the elution of daptomycin and tobramycin in
      calcium sulfate pellets over time and determined the dissolution rates of the
      pellets. Unlike other water-soluble antibiotics, daptomycin required special
      techniques to convert the calcium sulfate from a hemihydrate powder to a hardened
      dihydrate shape. The elution of daptomycin on day 1 (537 microg/mL/g) was greater
      than that from days 2, 3, 7, 10, 14, 21, and 28. The concentration fell to 153
      microg/mL/g and 37 microg/mL/g on days 2 and 3, respectively, then remained at
      between 5 microg/mL/g and 7 microg/mL/g for the remainder of the study. The
      elution behavior of the daptomycin pellets differed from that of the tobramycin
      containing pellets on days 1 through 3, but was similar from day 7 through day
      28. Daptomycin-containing pellets dissolved more rapidly in vitro than tobramycin
      containing pellets, although the importance of this more rapid dissolution in an
      in vivo situation is unknown. Using the techniques described in this paper,
      daptomycin can be incorporated within a calcium sulfate matrix.

PMID- 17549033
TI  - Vancomycin derivative photopolymerized to titanium kills S. epidermidis.
AB  - Infections in the setting of orthopaedic hardware remain a serious complication.
      Traditional treatment modalities rely on antibiotic-loaded biomaterials and/or
      prolonged intravenous therapy, both of which suffer major limitations. We
      hypothesized a derivatized form of the glycopeptide antibiotic vancomycin could
      be covalently attached to a Ti-6Al-4V implant alloy to form a bactericidal
      surface capable of killing bacteria relevant to orthopaedic infections. First, a
      polymerizable poly(ethylene glycol)-acrylate derivative of vancomycin was
      synthesized. This monomer was characterized by liquid chromatography, 1H NMR
      spectroscopy, and MIC and MBC determination. The monomer was subsequently
      photochemically polymerized to implant grade Ti-6Al-4V alloy. The coating was
      bactericidal against Staphylococcus epidermidis through initial release of
      unattached antibiotic species followed by continued surface-contact-mediated
      bacterial killing by covalently tethered vancomycin. Through this surface-contact
      mechanism, the number of colony forming units dropped by ca. fivefold from an
      initial inoculum of 1 x 10(6) cfu/mL over 4 hours and by ca. 100-fold with
      respect to nonbactericidal control surfaces. An inoculum of 1 x 10(4) cfu/mL was
      reduced to undetectable levels over 17 hours. This coating method allows a
      loading dose several thousand times larger than that achieved with monolayer
      vancomycin coupling approaches and holds promise for the treatment of orthopaedic
      infections.

PMID- 17549034
TI  - Vancomycin bound to Ti rods reduces periprosthetic infection: preliminary study.
AB  - A major challenge in treating periprosthetic infection is the predilection of
      certain bacteria to colonize implants, form biofilms, and resist treatment. We
      engineered an innovative self-protective implant with covalently bound
      antibiotics that prevents bacterial colonization and remains stable for extended
      periods of time. To test this surface in vivo, we developed a rat periprosthetic
      infection model with an intramedullary implant in S. aureus-infected femora.
      Using the model, we then evaluated the effect of vancomycin-modified titanium
      rods on the clinical presentation of bone infection. Finally, assuming delayed
      and chronic periprosthetic infections originate from biofilms atop contaminated
      implants, the numbers of surface adherent bacteria were measured to assess the
      capability of the implant to prevent biofilms. S. aureus (1.5 x 10(3) colony
      forming units) with no known resistance were injected into the femoral canal of
      Wistar rats, followed by the implant. Signs of infection were assessed weekly by
      direct clinical observation of the animals, radiograph, and microCT, and counts
      of bacteria adherent to the implant. Vancomycin-modified implants showed superior
      inhibition of bacterial attachment and proliferation compared to control titanium
      surfaces.

PMID- 17549035
TI  - Fasting triglyceride is a major determinant of postprandial triglyceride response
      in postmenopausal women.
AB  - OBJECTIVE: The purpose of the study was to examine the relative influences of
      fasting lipids, insulin resistance, and waist circumference (WC) on postprandial
      lipemia in postmenopausal women. DESIGN: Forty-nine naturally postmenopausal
      women were recruited for the study. Each woman underwent a 75-g oral glucose
      tolerance test to measure insulin resistance and a 1,000-kcal high-fat mixed meal
      test for postprandial triglyceride (TG) response. RESULTS: The participants were
      divided into three groups by tertiles of incremental TG response in the mixed
      meal test. The three groups were comparable in weight, WC, and fasting high
      density lipoprotein cholesterol (HDL-C) levels. There were significant
      differences in fasting TG and non-HDL-C concentrations among the three groups.
      The women in the high-tertile group were more insulin resistant than those in the
      low-tertile group, indicated by higher homeostasis model assessment for insulin
      resistance (HOMA-IR) values. The postprandial TG response was significantly
      correlated with Log(fasting TG), fasting non-HDL-C and Log(HOMA-IR), but not with
      WC, in univariate regression analyses. Log(fasting TG) was the only variable that
      remained significantly related to incremental TG response when all the above were
      entered into multiple regression models. Subsequently, we found that Log(HOMA-IR)
      and fasting non-HDL-C independently predicted the variance of Log(fasting TG) in
      stepwise multiple regression. CONCLUSIONS: Our data demonstrated that the fasting
      TG level is a major determinant of postprandial TG response in postmenopausal
      women. Insulin resistance and non-HDL-C may contribute independently to the
      fasting TG level. The influences of WC on postprandial lipemia seemed to be
      insignificant.

PMID- 17549036
TI  - Effects of estradiol and raloxifene on arterial thrombosis in ovariectomized
      mice.
AB  - OBJECTIVE: The effects of estrogen and selective estrogen receptor modulators
      (eg, raloxifene) on arterial thrombosis are not well defined. This study assessed
      the manner and mechanism by which estrogen and raloxifene affect homeostatic
      pathways in ovariectomized mice after acute arterial injury. DESIGN: Female mice
      (3 weeks old) underwent ovariectomy or sham operation. Five days after surgery,
      mice were assigned to treatment with estradiol (5.3 nmol/kg), raloxifene (2.7
      micromol/kg), or placebo (n = 10-12/group). The biological effects of both
      treatments were assessed by measurements of bone mass and the degree of uterine
      atrophy. After 4 months of therapy, carotid artery thrombosis was induced by
      photochemical injury, and the time to vascular occlusion was measured. RESULTS:
      Both treatments increased bone mineral density (4.1%-7.85%). Reversal of
      macroscopic uterine atrophy was observed only in estrogen-treated mice.
      Ovariectomized mice had a shorter time to occlusion compared with sham-operated
      mice (70.8 +/- 7.4 vs 103 +/- 11.3 min), suggesting accelerated thrombosis. Both
      estradiol and raloxifene significantly inhibited intra-arterial thrombosis in
      ovariectomized mice, prolonging the time to occlusion to 136.33 +/- 13.5 and
      141.43 +/- 9.26 min, respectively. Cyclooxygenase-2 levels in the lung tissue
      were significantly increased by both raloxifene and estradiol with endothelial
      nitric oxide synthase expression being unaltered. Platelet adhesion (measured by
      surface coverage under a shear rate of 1,800 s for 2 min) was significantly
      reduced in ovariectomized animals, being 4.63% +/- 1.47%, 5.78% +/- 1.58%, and
      10.04% +/- 1.33% for raloxifene, estradiol, and placebo, respectively.
      CONCLUSIONS: Ovariectomy amplifies thrombosis. We found that 4 months of
      treatment with both estradiol and raloxifene attenuates intravascular thrombosis.
      The antithrombotic effect was accompanied by increased expression of
      cyclooxygenase-2 and suppression of platelet surface adhesion.

PMID- 17549037
TI  - Low bone mineral density is associated with reduced hip joint space width in
      women: results from the Copenhagen Osteoarthritis Study.
AB  - OBJECTIVE: Since estrogen receptors (ER-alpha/ER-beta) were identified in human
      chondrocytes, animal and experimental studies have demonstrated the importance of
      continued estrogen production for the integrity of articular cartilage. However,
      human epidemiological support of the hypothesis has been inconclusive. The
      present cross-sectional study investigated the relationship between reduced bone
      mineral density (BMD), as a surrogate parameter of endogenous estrogen status
      assessed by digital x-ray radiogrammetry, and reduced minimum hip joint space
      width (JSW). DESIGN: Standardized hand radiographs of the Copenhagen
      Osteoarthritis Study cohort of 3,913 adults (1,470 male/2,443 female) with a mean
      age of 60 years (range, 18-92) were analyzed using X-Posure digital software,
      version 2.0 (Sectra-Pronosco). The system is operator independent. From 1,200
      individual measurements per radiograph, mean BMD was calculated. Minimum hip JSW
      was assessed on standardized pelvic radiographs. RESULTS: Digital x-ray
      radiogrammetry BMD decreased in both men and women after the age of 45 years,
      progressively more so in women. Although minimum hip JSW in men remained
      relatively unaltered throughout life, a marked decline in female minimum hip JSW
      after age 45 years was observed. We found moderate but highly significant
      relationships between reduced BMD and reduced hip JSW in women (P < 0.0001),
      adjusted for age and dysplastic joint incongruity. CONCLUSION: We believe that
      the present study supports the hypothetical relationship between reduced estrogen
      levels and hip JSW reduction in women.

PMID- 17549039
TI  - Letter to the Editor.

PMID- 17549038
TI  - Conducting cross-cultural research in teams and the search for the "culture
      proof" variable.
AB  - OBJECTIVE: Cross-cultural research must always deal with the problem that meaning
      systems and behaviors cannot be readily compared from one culture to the next
      because the sociocultural context can vary so widely. DESIGN: The organizers of
      Project AGE: Age, Generation, and Experience, a multicultural study of aging,
      recognized this problem and devised instruments for studying age that allowed for
      cultural variation as well as researchers made every effort to gain an emic
      understanding (understanding based on categories recognized by the local
      respondents) of people's attitudes about aging in the several cultures in which
      we worked. For comparison to take place, we needed to use similar question frames
      to elicit comparable information across societies of different types. RESULTS:
      Many questions put to people about their attitudes toward their own and other
      persons' aging were readily understood by our respondents. But some topics proved
      difficult to investigate systematically across cultures. CONCLUSIONS: In
      hindsight, we could have achieved additional value from our interviews if we had
      incorporated some independent measures of physical health and capacity. Such data
      would have added depth to our discussion of within-site and across-site
      differences on both the independent measures themselves and their possible
      correlation with attitudinal data.

PMID- 17549040
TI  - Potential use of biomarkers for analyzing interpopulation and cross-cultural
      variability in reproductive aging.
AB  - OBJECTIVE: The aims of this study were (1) to document the extent of variability
      in physiological aspects of reproductive aging; (2) to outline those areas where
      more work is needed to expand our knowledge of this variability; (3) to outline
      available biomarkers that can be used to measure aspects of reproductive aging,
      such as ovarian reserve and declining hormone levels; and (4) to note potential
      problems with the use of these biomarkers in cross-cultural settings. DESIGN:
      Literature review of English and French publications using PubMed with no date
      restrictions. RESULTS: Substantial variability exists in both cultural and
      physiological aspects of reproductive aging and menopause. However, the extent of
      variability across populations for many areas of reproductive aging needs better
      documentation as well as explanation of sources of this variability. Several
      biomarkers exist for use in cross-cultural research, including ovarian
      characteristics such as ovarian volume, ovarian reserve, follicular development,
      and atresia, and levels of hormones such as follicle-stimulating hormone, inhibin
      B, and anti-mullerian hormone. CONCLUSION: We urge that further work be
      undertaken to evaluate and describe variability in physiological aspects of
      reproductive aging in cross-cultural settings. Some problems exist in the use of
      biomarkers to record this variability, particularly in remote settings with few
      logistical resources.

PMID- 17549041
TI  - Re: Early postmenopausal hormone therapy improves postural balance.

PMID- 17549042
TI  - Preservation of mitochondrial function may contribute to cardioprotective effects
      of Na+/Ca2+ exchanger inhibitors in ischaemic/reperfused rat hearts.
AB  - BACKGROUND AND PURPOSE: Na+/Ca2+ exchanger (NCX) inhibitors are known to
      attenuate myocardial reperfusion injury. However, the exact mechanisms for the
      cardioprotection remain unclear. The present study was undertaken to examine the
      mechanism underlying the cardioprotection by NCX inhibitors against
      ischaemia/reperfusion injury. EXPERIMENTAL APPROACH: Isolated rat hearts were
      subjected to 35-min ischaemia/60-min reperfusion or 20-min ischaemia/60-min
      reperfusion. NCX inhibitors (3-30 microM KB-R7943 (KBR) or 0.3-1 microM SEA0400
      (SEA)) were given for 5 min prior to ischaemia (pre-ischaemic treatment) or for
      10 min after the onset of reperfusion (post-ischaemic treatment). KEY RESULTS:
      With 35-min ischaemia/60-min reperfusion, pre- or post-ischaemic treatment with
      KBR or SEA neither enhanced post-ischaemic contractile recovery nor attenuated
      ischaemia- or reperfusion-induced Na+ accumulation and damage to mitochondrial
      respiratory function. With the milder model (20-min ischaemia/reperfusion), pre-
      or post-ischaemic treatment with 10 microM KBR or 1 microM SEA significantly
      enhanced the post-ischaemic contractile recovery, associated with reductions in
      reperfusion-induced Ca2+ accumulation, damage to mitochondrial function, and
      decrease in myocardial high-energy phosphates. Furthermore, Na+ influx to
      mitochondria in vitro was enhanced by increased concentrations of NaCl. KBR (10
      microM) and 1 microM SEA partially decreased the Na+ influx. CONCLUSIONS AND
      IMPLICATIONS: The NCX inhibitors exerted cardioprotective effects during
      relatively mild ischaemia. The mechanism may be attributable to prevention of
      mitochondrial damage, possibly mediated by attenuation of Na+ overload in cardiac
      mitochondria during ischaemia and/or Ca2+ overload via the reverse mode of NCX
      during reperfusion.

PMID- 17549043
TI  - Dimethyl sulphoxide relaxes rabbit detrusor muscle by decreasing the Ca2+
      sensitivity of the contractile apparatus.
AB  - BACKGROUND AND PURPOSE: The intravesical administration of dimethyl sulphoxide
      (DMSO) is used to alleviate the symptoms of interstitial cystitis. We
      investigated the relaxant effect of DMSO and its underlying mechanism in the
      detrusor muscle. EXPERIMENTAL APPROACH: The effects of DMSO on contraction, on
      Ca2+ sensitivity of myofilaments, and on myosin light chain (MLC) phosphorylation
      were investigated in both intact and alpha-toxin-permeabilized strips of rabbit
      detrusor muscle. KEY RESULTS: In fura-PE3-loaded strips, DMSO (>1%) induced a
      significant relaxation during sustained contractions induced by 60 mM K+
      depolarization or 10 microM carbachol, while having no effect on the [Ca2+](i)
      level. DMSO decreased the level of MLC phosphorylation during the contractions
      induced by 60 mM K+ and 10 microM carbachol. DMSO also inhibited both the
      contraction and MLC phosphorylation induced by calyculin-A in intact strips. In
      the alpha-toxin-permeabilized preparations, DMSO relaxed the Ca2+-induced
      contraction and also inhibited the tension development induced by a stepwise
      increment of Ca2+ concentrations. Such a relaxant effect of DMSO was enhanced in
      the presence of phosphate. CONCLUSIONS AND IMPLICATIONS: DMSO relaxes rabbit
      detrusor muscle by decreasing the Ca2+ sensitivity of myofilaments. Inhibition of
      the kinase activities involved in myosin phosphorylation may play a major role in
      DMSO-induced Ca2+ desensitization. Inhibition of the cross-bridge cycling at the
      step of phosphate release may also contribute to the relaxant effect of DMSO.
      Such relaxant effects of DMSO could be linked to the therapeutic effect of DMSO
      in interstitial cystitis.

PMID- 17549044
TI  - Late-phase, protein synthesis-dependent long-term potentiation in hippocampal CA1
      pyramidal neurones with destabilized microtubule networks.
AB  - BACKGROUND AND PURPOSE: Protein synthesis-dependent late-long term potentiation
      (L-LTP) is an enduring form of synaptic plasticity that has been shown to rely
      on, at least partly, protein synthesis at synaptic and/or dendritic sites.
      Evidence suggests that somatic transcription of new mRNAs may provide a
      significant contribution to the availability of mRNAs at synaptic sites where
      they are made available for dendritic translation. Transport of mRNAs from
      somatic to dendritic sites might be expected to involve movement along a
      microtubule network. In this study we examined whether it was possible to
      maintain L-LTP in hippocampal slices with destabilized microtubule networks.
      EXPERIMENTAL APPROACH: Extracellular field excitatory postsynaptic potentials
      (fEPSPs) were recorded from rat hippocampal slices and following a period of
      baseline recording, stimuli were given that induced LTP. LTP was monitored for 5
      h in both control slices and slices treated with vincristine to depolymerize
      tubulin. KEY RESULTS: L-LTP was induced and maintained in vincristine-treated
      slices. Four hours after tetanic stimulation fEPSPs were 196+/-19% of baseline
      values. The magnitude of potentiation was similar to that seen in untreated
      slices (175+/-15%). L-LTP in vincristine-treated slices was, however, not
      maintained in the presence of the protein synthesis inhibitor, rapamycin.
      Immunohistochemistry and confocal microscopy of vincristine-treated slices
      verified that the microtubule network had been destabilized. CONCLUSIONS AND
      IMPLICATIONS: Communication between somatic and synaptic sites through protein
      and/or mRNA trafficking via an intact microtubule network is not required for
      protein synthesis dependent L-LTP.

PMID- 17549045
TI  - Pharmacological enhancement of the endocannabinoid system in the nucleus
      accumbens shell stimulates food intake and increases c-Fos expression in the
      hypothalamus.
AB  - BACKGROUND AND PURPOSE: Evidence indicates that the endocannabinoid, 2
      arachidonoylglycerol (2-AG), increases food intake when injected into the nucleus
      accumbens shell (NAcS), thereby potentially activating hypothalamic nuclei
      involved in food intake regulation. We aimed to evaluate potential orexigenic
      effects of the endocannabinoid anandamide and of AA5HT, a fatty acid amide
      hydrolase (FAAH) inhibitor, and OMDM-1, an inhibitor of anandamide uptake,
      injected in the NAcS, as well as the effect of these treatments on activation of
      hypothalamic nuclei. EXPERIMENTAL APPROACH: Drugs were given into the NAcS of
      rats and food intake quantified during the next 4 h. In other groups, after the
      same treatments the brains were processed for c-Fos immunohistochemistry with
      focus on hypothalamic nuclei. Additional groups were used to quantify
      endocannabinoid levels in the nucleus accumbens and the hypothalamus after AA5HT
      and OMDM-1 intra-NAcS injections. KEY RESULTS: Our results indicate that the
      above treatments stimulate food intake during 4 h post-injection. They also
      increase c-Fos immunoreactivity in hypothalamic nuclei. The CB(1) antagonist,
      AM251, blocked these effects. Finally, we found elevated levels of 2-AG, but not
      anandamide, after intra-NAcS injections of AA5HT. CONCLUSIONS AND IMPLICATIONS:
      These data support the involvement of the endocannabinoid system in feeding
      behavior at the level of the NAcS and hypothalamus. In addition, this is the
      first experimental demonstration that the pharmacological inhibition of
      endocannabinoid inactivation in the NAcS stimulates food intake, suggesting that
      the endocannabinoid degrading proteins can be a target for treating eating
      disorders.

PMID- 17549046
TI  - In silico pharmacology for drug discovery: applications to targets and beyond.
AB  - Computational (in silico) methods have been developed and widely applied to
      pharmacology hypothesis development and testing. These in silico methods include
      databases, quantitative structure-activity relationships, similarity searching,
      pharmacophores, homology models and other molecular modeling, machine learning,
      data mining, network analysis tools and data analysis tools that use a computer.
      Such methods have seen frequent use in the discovery and optimization of novel
      molecules with affinity to a target, the clarification of absorption,
      distribution, metabolism, excretion and toxicity properties as well as
      physicochemical characterization. The first part of this review discussed the
      methods that have been used for virtual ligand and target-based screening and
      profiling to predict biological activity. The aim of this second part of the
      review is to illustrate some of the varied applications of in silico methods for
      pharmacology in terms of the targets addressed. We will also discuss some of the
      advantages and disadvantages of in silico methods with respect to in vitro and in
      vivo methods for pharmacology research. Our conclusion is that the in silico
      pharmacology paradigm is ongoing and presents a rich array of opportunities that
      will assist in expediting the discovery of new targets, and ultimately lead to
      compounds with predicted biological activity for these novel targets.

PMID- 17549047
TI  - In silico pharmacology for drug discovery: methods for virtual ligand screening
      and profiling.
AB  - Pharmacology over the past 100 years has had a rich tradition of scientists with
      the ability to form qualitative or semi-quantitative relations between molecular
      structure and activity in cerebro. To test these hypotheses they have
      consistently used traditional pharmacology tools such as in vivo and in vitro
      models. Increasingly over the last decade however we have seen that computational
      (in silico) methods have been developed and applied to pharmacology hypothesis
      development and testing. These in silico methods include databases, quantitative
      structure-activity relationships, pharmacophores, homology models and other
      molecular modeling approaches, machine learning, data mining, network analysis
      tools and data analysis tools that use a computer. In silico methods are
      primarily used alongside the generation of in vitro data both to create the model
      and to test it. Such models have seen frequent use in the discovery and
      optimization of novel molecules with affinity to a target, the clarification of
      absorption, distribution, metabolism, excretion and toxicity properties as well
      as physicochemical characterization. The aim of this review is to illustrate some
      of the in silico methods for pharmacology that are used in drug discovery.
      Further applications of these methods to specific targets and their limitations
      will be discussed in the second accompanying part of this review.

PMID- 17549048
TI  - Species-specific in vitro pharmacological effects of the cannabinoid receptor 2
      (CB2) selective ligand AM1241 and its resolved enantiomers.
AB  - BACKGROUND AND PURPOSE: Racemic (R,S) AM1241 is a cannabinoid receptor 2 (CB(2))
      selective aminoalkylindole with antinociceptive efficacy in animal pain models.
      The purpose of our studies was to provide a characterization of R,S-AM1241 and
      its resolved enantiomers in vitro and in vivo. EXPERIMENTAL APPROACH: Competition
      binding assays were performed using membranes from cell lines expressing
      recombinant human, rat, and mouse CB(2) receptors. Inhibition of cAMP was assayed
      using intact CB(2)-expressing cells. A mouse model of visceral pain (para
      phenylquinone, PPQ) and a rat model of acute inflammatory pain (carrageenan) were
      employed to characterize the compounds in vivo. KEY RESULTS: In cAMP inhibition
      assays, R,S-AM1241 was found to be an agonist at human CB(2), but an inverse
      agonist at rat and mouse CB(2) receptors. R-AM1241 bound with more than 40-fold
      higher affinity than S-AM1241, to all three CB(2) receptors and displayed a
      functional profile similar to that of the racemate. In contrast, S-AM1241 was an
      agonist at all three CB(2) receptors. In pain models, S-AM1241 was more
      efficacious than either R-AM1241 or the racemate. Antagonist blockade
      demonstrated that the in vivo effects of S-AM1241 were mediated by CB(2)
      receptors. CONCLUSIONS AND IMPLICATIONS: These findings constitute the first in
      vitro functional assessment of R,S-AM1241 at rodent CB(2) receptors and the first
      characterization of the AM1241 enantiomers in recombinant cell systems and in
      vivo. The greater antinociceptive efficacy of S-AM1241, the functional CB(2)
      agonist enantiomer of AM1241, is consistent with previous observations that CB(2)
      agonists are effective in relief of pain.

PMID- 17549050
TI  - Double pharmacological challenge on repolarization opens new avenues for drug
      safety research.
AB  - The pharmaceutical industry is testing new potential drugs for their propensity
      to prolong human cardiac repolarization, and regards this as a sign of
      proarrhythmic risk. Many studies have dethroned the common perception that
      prolonged repolarization is a reliable surrogate marker for torsades de pointes
      (TdP) arrhythmia. Both the pharmaceutical industry and the regulatory bodies are
      neglecting the available proarrhythmia models. In vitro studies have suggested
      that combined pharmacological hits on repolarization will produce a superior
      substrate for in vivo proarrhythmia, compared to the single-drug assessment. By
      using consecutive pharmacological challenges, a simple model is proposed, in
      which combinatorial pharmacology is employed to provoke TdP in the conscious dog.
      The pharmaceutical industry interested in evaluating the proarrhythmic potential
      of their present and future drugs now has a simple means of doing so.

PMID- 17549049
TI  - Activation of the ERK signalling pathway contributes to the adaptive changes in
      rat hearts during naloxone-induced morphine withdrawal.
AB  - BACKGROUND AND PURPOSE: We have previously demonstrated that morphine withdrawal
      induced hyperactivity of the heart by activation of noradrenergic pathways
      innervating the left and right ventricle, as evaluated by noradrenaline turnover
      and c-Fos expression. The extracellular signal-regulated kinase (ERK) has been
      implicated in drug addiction, but its role in activation of the heart during
      morphine dependence remains poorly understood. Here, we have looked for
      activation of ERK during morphine withdrawal and if this activation induced gene
      expression. EXPERIMENTAL APPROACH: Dependence on morphine was induced by s.c.
      implantation of morphine pellets for 7 days. Morphine withdrawal was precipitated
      on day 8 by injection of naloxone (2 mg kg(-1), s.c.). ERK1/2, their
      phosphorylated forms and c-Fos were measured by western blotting and
      immunohistochemistry of cardiac tissue. KEY RESULTS: Naloxone-induced morphine
      withdrawal activated ERK1/2 and increased c-Fos expression in cardiac tissues. c
      Fos expression was blocked by SL327, a drug that prevents ERK activation.
      CONCLUSIONS AND IMPLICATIONS: These results indicate that signalling through the
      ERKs is necessary for morphine withdrawal-induced hyperactivity of the heart and
      suggest that this pathway may also be involved in activation of immediate-early
      genes in both cytosolic and nuclear effector mechanisms that have the potential
      to bring about long-term changes in the heart.

PMID- 17549052
TI  - Toxic serum levels of tacrolimus after topical administration in an infant with
      severe cutaneous graft-versus-host disease.

PMID- 17549051
TI  - Anti-adipogenic action of pitavastatin occurs through the coordinate regulation
      of PPARgamma and Pref-1 expression.
AB  - BACKGROUND AND PURPOSE: Adipocyte differentiation in vitro is coordinately
      activated by two transcription factors, peroxisome proliferator-activated
      receptor gamma (PPARgamma) and CCAAT enhancer binding protein alpha (C/EBPalpha),
      but it is inhibited by preadipocyte factor-1 (pref-1). Statins, inhibitors of HMG
      CoA reductase and de novo cholesterol synthesis, can have pleiotropic effects
      which influence adipocyte phenotype by ill-defined mechanisms. We investigated
      the effects of pitavastatin (NK-104) on adipocyte differentiation and the
      transcriptional pathways involved. EXPERIMENTAL APPROACH: The effects of
      pitavastatin on adipocyte differentiation were evaluated by the formation of oil
      droplets, content of cellular triglyceride and expression of adipocyte-specific
      genes. Regulatory mechanisms were assessed by analysis of PPARgamma, C/EBPalpha
      and pref-1 expression. KEY RESULTS: Pitavastatin significantly inhibited
      adipocyte differentiation of 3T3-L1 preadipocytes in response to adipogenic
      inducers. Evidence for inhibition included fewer Oil Red O positive droplets,
      less cellular triglyceride and decreased expression of adipocyte-specific genes,
      including fatty acid binding protein (aP2), CD36, adipsin and glucose transporter
      4 (GLUT4). The inhibitory effects of pitavastatin on adipocyte differentiation of
      3T3-L1 preadipocytes were time and concentration dependent. Pitavastatin
      significantly blocked induction of PPARgamma expression, but not C/EBPalpha
      expression or DNA binding activity of PPARgamma. Also, pitavastatin induced pref
      1 expression in preadipocytes and maintained expression of pref-1 at high levels
      in differentiated cells. CONCLUSIONS AND IMPLICATIONS: Our data suggest that
      pitavastatin inhibits adipocyte differentiation by blocking PPARgamma expression
      and activating pref-1 expression. These studies may have implications in the
      regulation of adipogenesis in response to statins.

PMID- 17549053
TI  - Treatment of refractory chronic GVHD with rituximab: a GITMO study.
AB  - The anti-CD20 chimaeric monoclonal antibody Rituximab has recently been shown to
      induce significant clinical response in a proportion of patients with refractory
      chronic graft-versus-host disease (cGVHD). We now report 38 patients, median age
      48 years (22-61), receiving Rituximab for refractory cGVHD, assessed for clinical
      response and survival. Median duration of cGVHD before Rituximab was 23 months
      (range 2-116), the median number of failed treatment lines was 3 (range 1 to > or
      =6) and the median follow-up after Rituximab was 11 months (1-88). Overall
      response rate was 65%: skin 17/20 (63%), mouth 10/21 (48%), eyes 6/14 (43%),
      liver 3/12 (25%), lung 3/8 (37.5%), joints 4/5, gut 3/4, thrombocytopaenia 2/3,
      vagina 0/2, pure red cell aplasia 0/1 and, myasthenia gravis 1/1. During the
      study period 8/38 died: causes of death were cGVHD progression (n=3), disease
      relapse (n=1), infection (n=3), sudden death (n=1). The actuarial 2 year survival
      is currently 76%. We confirm that Rituximab is effective in over 50% of patients
      with refractory cGVHD and may have a beneficial impact on survival.

PMID- 17549054
TI  - Prophylactic fresh frozen plasma may prevent development of hepatic VOD after
      stem cell transplantation via ADAMTS13-mediated restoration of von Willebrand
      factor plasma levels.
AB  - We initially conducted a multicenter, randomized trial (n=43), and subsequently a
      questionnaire study (n=209) of participating hospitals, to evaluate whether
      infused fresh frozen plasma (FFP) could prevent the occurrence of hepatic veno
      occlusive disease (VOD) after stem cell transplantation (SCT). Forty-three
      patients were divided into two groups: 23 receiving FFP infusions and 20 not
      receiving it. VOD developed in three patients not receiving FFP. Plasma von
      Willebrand factor (VWF) antigen levels were lower at days 0, 7 and 28 after SCT
      in patients receiving FFP than in those not receiving it, whereas plasma ADAMTS13
      activity (ADAMTS13:AC) did not differ between them. Plasma VWF multimer (VWFM)
      was demonstrated to be defective in the high approximately intermediate VWFM
      during the early post-SCT phase, but there was a significant increase in high
      VWFM just before VOD onset. This suggests that a relative enzyme-to-substrate
      (ADAMTS13/high-VWFM) imbalance is involved in the pathogenesis of VOD. To
      strengthen this hypothesis, the incidence of VOD was apparently lower in patients
      receiving FFP infusions than in those not receiving it (0/23 vs 3/20) in the
      randomized trial. Further, the results combined with the subsequent questionnaire
      study (0/36 vs 11/173) clearly showed the incidence to be statistically
      significant (0/59 vs 14/193, P=0.033).

PMID- 17549055
TI  - Neurotoxicity of levodopa: treatment-associated homocysteine increase.

PMID- 17549056
TI  - Academic neurology and industry: open doors or firewalls?

PMID- 17549057
TI  - Collaboration to promote neurological research--the European Brain Council
      experience.

PMID- 17549058
TI  - Etiology and management of refractory epilepsies.
AB  - The epilepsies are an important, common and diverse group of symptom complexes
      characterized by recurrent spontaneous seizures. Although many patients with
      epilepsy have their seizures controlled effectively by antiepileptic drugs
      (AEDs), about one-third of patients continue to have seizures, despite trying a
      range of AEDs. Such patients bear the heaviest burden of epilepsy, with increased
      morbidity and risk of premature mortality. Our current understanding of the
      refractory epilepsies--the most common of which are focal--is limited; even their
      definition is problematic. Standard treatments for refractory epilepsies include
      optimization of existing AED regimens, trials of further AEDs, and, for some
      patients, therapeutic resective neurosurgery. Recent basic research has explored
      possible underlying causes of refractory epilepsy, and two main hypotheses have
      emerged to account for the failure of AED treatment. According to one hypothesis,
      AEDs might fail because of alterations in the properties of their usual targets.
      Alternatively, they might fail because multidrug transporter mechanisms limit
      concentrations of the drugs at their targets. The refractory epilepsies can be
      viewed as offering remarkable insights into biological processes in the
      epilepsies, and their effective treatment remains an important aim; treatment
      would potentially bring much-needed relief to hundreds of thousands of patients
      across the world.

PMID- 17549059
TI  - Diabetic neuropathy--a review.
AB  - Diabetic neuropathy is the most common neuropathy in industrialized countries,
      and it is associated with a wide range of clinical manifestations. The vast
      majority of patients with clinical diabetic neuropathy have a distal symmetrical
      form of the disorder that progresses following a fiber-length-dependent pattern,
      with sensory and autonomic manifestations predominating. This pattern of
      neuropathy is associated with a progressive distal axonopathy. Patients
      experience pain, trophic changes in the feet, and autonomic disturbances.
      Occasionally, patients with diabetes can develop focal and multifocal
      neuropathies that include cranial nerve involvement and limb and truncal
      neuropathies. This neuropathic pattern tends to occur after 50 years of age, and
      mostly in patients with long-standing diabetes mellitus. Length-dependent
      diabetic polyneuropathy does not show any trend towards improvement, and either
      relentlessly progresses or remains relatively stable over a number of years.
      Conversely, the focal diabetic neuropathies, which are often associated with
      inflammatory vasculopathy on nerve biopsies, remain self-limited, sometimes after
      a relapsing course.

PMID- 17549060
TI  - Technology insight: can neuroimaging provide insights into the role of ischemia
      in Balo's concentric sclerosis?
AB  - Balo's concentric sclerosis (BCS) has long been considered to be a variant of
      multiple sclerosis. Although BCS was initially described over 100 years ago,
      relatively few antemortem cases have been identified, and the exact pathogenesis
      remains unknown. Inflammatory protective ischemic preconditioning has recently
      been suggested as a mechanism by which the typical concentric rings of the BCS
      lesion are formed. Advanced neuroimaging can provide important in vivo markers of
      disease progression that can assist in the diagnosis and management of patients
      with BCS. In this Review, we discuss evidence from longitudinal neuroimaging
      studies that supports the role of ischemic preconditioning in BCS.

PMID- 17549061
TI  - Balo's concentric sclerosis presenting as a stroke-like syndrome.
AB  - BACKGROUND: A 37-year-old woman without important previous medical history
      presented to an emergency room with acute onset of left-sided weakness and
      numbness. Examination revealed left-sided hemiparesis (in the arm greater than in
      the leg) and hypoesthesia. INVESTIGATIONS: Routine laboratory testing, lumbar
      puncture, dynamic susceptibility contrast perfusion study, longitudinal brain
      MRI, and magnetic resonance spectroscopy were performed. DIAGNOSIS: Balos
      concentric sclerosis. MANAGEMENT: Intravenous methylprednisolone followed by oral
      steroid taper.

PMID- 17549062
TI  - Dopaminergic genotype biases spatial attention in healthy children.
AB  - In everyday life, our sensory system is bombarded with visual input and we rely
      upon attention to select only those inputs that are relevant to behavioural
      goals. Typically, humans can shift their attention from one visual field to the
      other with little cost to perception. In cases of 'unilateral neglect', however,
      there is a persistent bias of spatial attention towards the same side as the
      damaged cerebral hemisphere. We used a visual orienting task to examine the
      influence of functional polymorphisms of the dopamine transporter gene (DAT1) on
      individual differences in spatial attention in normally developing children. DAT1
      genotype significantly influenced spatial bias. Healthy children who were
      homozygous for alleles that influence the expression of dopamine transporters in
      the brain displayed inattention for left-sided stimuli, whereas heterozygotes did
      not. Our data provide the first evidence in healthy individuals of a genetically
      mediated bias in spatial attention that is related to dopamine signalling.

PMID- 17549063
TI  - Pharmacogenetics and pharmacogenomics of schizophrenia: a review of last decade
      of research.
AB  - The last decade of research into the pharmacogenetics of antipsychotics has seen
      the development of genetic tests to determine the patients' metabolic status and
      the first attempts at personalization of antipsychotic treatment. The most
      significant results are the association between drug metabolic polymorphisms,
      mainly in cytochrome P450 genes, with variations in drug metabolic rates and side
      effects. Patients with genetically determined CYP2D6 poor metabolizer (PMs)
      status may require lower doses of antipsychotic. Alternatively, CYP2D6 ultrarapid
      matabolizers (UMs) will need increased drug dosage to obtain therapeutic
      response. Additionally, polymorphisms in dopamine and serotonin receptor genes
      are repeatedly found associated with response phenotypes, probably reflecting the
      strong affinities that most antipsychotics display for these receptors. In
      particular, there is important evidence suggesting association between dopamine 2
      receptor (D2) polymorphisms (Taq I and -141-C Ins/Del) and a dopamine 3 receptor
      (D3) polymorphism (Ser9Gly) with antipsychotic response and drug-induced tardive
      dyskinesia. Additionally, there is accumulating evidence indicating the influence
      of a 5-HT2C polymorphism (-759-T/C) in antipsychotic-induced weight gain.
      Application of this knowledge to clinical practice is slowly gathering pace, with
      pretreatment determination of individual's drug metabolic rates, via CYP
      genotyping, leading the field. Genetic determination of patients' metabolic
      status is expected to bring clinical benefits by helping to adjust therapeutic
      doses and reduce adverse reactions. Genetic tests for the pretreatment prediction
      of antipsychotic response, although still in its infancy, have obvious
      implications for the selection and improvement of antipsychotic treatment. These
      developments can be considered as successes, but the objectives of bringing
      pharmacogenetic and pharmacogenomic research in psychiatric clinical practice are
      far from being realized. Further development of genetic tests is required before
      the concept of tailored treatment can be applied to psychopharmatherapy. This
      review aims to summarize the key findings from the last decade of research in the
      field. Current knowledge on genetic prediction of drug metabolic status, general
      response and drug-induced side effects will be reviewed and future
      pharmacogenomic and epigenetic research will be discussed.

PMID- 17549064
TI  - The nuclear envelope and transcriptional control.
AB  - Cells have evolved sophisticated multi-protein complexes that can regulate gene
      activity at various steps of the transcription process. Recent advances highlight
      the role of nuclear positioning in the control of gene expression and have put
      nuclear envelope components at centre stage. On the inner face of the nuclear
      envelope, active genes localize to nuclear-pore structures whereas silent
      chromatin localizes to non-pore sites. Nuclear-pore components seem to not only
      recruit the RNA-processing and RNA-export machinery, but contribute a level of
      regulation that might enhance gene expression in a heritable manner.

PMID- 17549065
TI  - The versatile worm: genetic and genomic resources for Caenorhabditis elegans
      research.
AB  - Since its establishment as a model organism, Caenorhabditis elegans has been an
      invaluable tool for biological research. An immense spectrum of questions can be
      addressed using this small nematode, making it one of the most versatile and
      exciting model organisms. Although the many tools and resources developed by the
      C. elegans community greatly facilitate new discoveries, they can also overwhelm
      newcomers to the field. This Review aims to familiarize new worm researchers with
      the main resources, and help them to select the tools that are best suited for
      their needs. We also hope that it will be helpful in identifying new research
      opportunities and will promote the development of additional resources.

PMID- 17549066
TI  - Linkage of nicotine dependence and smoking behavior on 10q, 7q and 11p in twins
      with homogeneous genetic background.
AB  - The significant worldwide health burden introduced by tobacco smoking highlights
      the importance of studying the genetic determinants of smoking behavior and the
      key factor sustaining compulsive smoking, that is, nicotine dependence (ND). We
      have here addressed the genetic background of smoking in a special study sample
      of twins, harmonized for early life events and specifically ascertained for
      smoking from the nationwide twin cohort of the genetically unique population of
      Finland. The twins and their families were carefully examined for extensive
      phenotype profiles and a genome-wide scan was performed to identify loci behind
      the smoking status, ND and the comorbid phenotype of ND and alcohol use in 505
      individuals from 153 families. We replicated previous linkage findings on 10q
      (max logarithm of the odds (LOD) 3.12) for a smoker phenotype, and on 7q and 11p
      (max LOD 2.50, and 2.25, respectively) for the ND phenotype. The loci linked for
      ND also showed evidence for linkage for the comorbid phenotype. Our study
      provides confirmatory evidence for the involvement of these genome regions in the
      genetic etiology of smoking behavior and ND and for the first time associates
      drinking and smoking to a shared locus on 10q.

PMID- 17549068
TI  - The clinical role of genetic polymorphisms in drug-metabolizing enzymes.
AB  - For most drug-metabolizing enzymes (DMEs), the functional consequences of genetic
      polymorphisms have been examined. Variants leading to reduced or increased
      enzymatic activity as compared to the wild-type alleles have been identified.
      This review tries to define potential fields in the therapy of major medical
      conditions where genotyping (or phenotyping) of genetically polymorphic DMEs
      might be beneficial for drug safety or therapeutic outcome. The possible
      application of genotyping is discussed for depression, cardiovascular diseases
      and thromboembolic disorders, gastric ulcer, malignant diseases and tuberculosis.
      Some drugs used for relief of these ailments are metabolized with participation
      of genetically polymorphic DMEs including CYP2D6, CYP2C9, CYP2C19, thiopurine-S
      methyltransferase, dihydropyrimidine dehydrogenase, uridine diphosphate
      glucuronosyltransferase and N-acetyltransferase type 2. Current evidence suggests
      that taking genetically determined metabolic capacities of DMEs into account has
      the potential to improve individual risk/benefit relationship. However, more
      prospective studies with clinical endpoints are needed before the paradigm of
      'personalized medicine' based on DME variants can be established.

PMID- 17549069
TI  - Open prostatectomy for benign prostate hyperplasia: short-term outcome in 3000
      consecutive patients.
AB  - The purpose of this study was to report the short-term results of open
      prostatectomy for benign prostatic hyperplasia (BPH). Patient charts were
      retrospectively reviewed from September 1988 to April 2004. A total of 3000
      consecutive patients with bothersome lower urinary tract symptoms (LUTS) and
      complications of BPH underwent open prostatectomy in our center. We routinely
      used a retropubic, transcapsular approach with spinal anesthesia. Mean age was 69
      years. Three hundred and sixty one patients were 80 years or older. Mean prostate
      volume was 71 ml. One thousand eight hundred and twenty five patients (60.8%)
      presented with and were operated on for acute urinary retention (AUR), and 350
      patients (11.7%) presented with and were operated on for urge/overflow urinary
      incontinence. The main reasons for delayed presentation were poverty and absence
      of real medical insurance, because in Iran 'insured' patients pay at least 60% of
      their medical expenses personally. Reoperation in the same admission was needed
      in 29 patients (1%). Transfusions were needed in 99 patients (3.3%). Wound
      infection occurred in 37 patients (1.2%). Acute myocardial infarction (MI)
      occurred in 15 patients (0.5%), resulting in three deaths. Occurrence of AUR had
      significant negative correlation with duration of symptoms (P<0.05; odds ratio
      0.5), and significant positive correlation with positive urine culture (P<0.05;
      odds ratio 2.7). Duration of hospital stay had significant positive correlation
      with positive urine culture (P<0.05; odds ratio 1.6) and advanced age (P<0.05;
      odds ratio 1.8), and significant negative correlation with prostate volume
      (P<0.05; odds ratio 0.6). Our results are representative of the current status of
      open prostatectomy. Whenever minimally invasive therapies are not affordable
      retropubic prostatectomy is a practical alternative.

PMID- 17549067
TI  - Pharmacogenetic profiling in patients with advanced colorectal cancer treated
      with first-line FOLFIRI chemotherapy.
AB  - The primary end point of the study was the analysis of associations between
      polymorphisms with putative influence on 5-fluorouracil/irinotecan activity and
      progression-free survival (PFS) of patients with advanced colorectal cancer
      treated with first-line FOLFIRI chemotherapy. Peripheral blood samples from 146
      prospectively enrolled patients were used for genotyping polymorphisms in
      thymidylate synthase (TS), methylenetetrahydrofolate reductase (MTHFR), excision
      repair cross-complementation group-1 (ERCC 1) xeroderma pigmentosum group-D
      (XPD), X-ray cross-complementing-1 (XRCC 1), X-ray cross-complementing-3 (XRCC 3)
      and uridine diphosphate-glucuronosyltransferases-A1 (UGT1 A1). TS 3'-UTR 6+/6+
      and XRCC3-241 C/C genotypes were associated with adverse PFS. Hazard ratio for
      PFS achieved 2.89 (95% confidence interval=1.56-5.80; P=0.002) in 30 patients
      (20%) with both risk genotypes. Risk for Grade III-IV neutropenia was
      significantly associated with UGT1A1*28 7/7 genotype. These promising findings
      deserve further investigations and their validation in independent prospective
      studies.

PMID- 17549070
TI  - Transcriptional, post-transcriptional and post-translational regulations of gene
      expression during leaf polarity formation.
AB  - Leaf morphogenesis requires the establishment of adaxial-abaxial polarity after
      primordium initiation from the shoot apical meristem (SAM). Several families of
      transcription factors are known to play critical roles in promoting adaxial or
      abaxial leaf fate. Recently, post-transcriptional gene silencing pathways have
      been shown to regulate the establishment of leaf polarity, providing novel and
      exciting insights into leaf development. For example, microRNAs (miR165/166) and
      a trans-acting siRNA (TAS3-derived tasiR-ARF) have been shown to repress the
      expression of several key transcription factor genes. In addition, yet another
      level of regulation, post-translational regulation, has been revealed recently by
      studies on the role of the 26S proteasome in leaf polarity. Although our
      understanding regarding the molecular mechanisms underlying establishment of
      adaxial-abaxial polarity has greatly improved, there is still much that remains
      elusive. This review aims to discuss recent progress, as well as the remaining
      questions, regarding the molecular mechanisms underlying leaf polarity formation.

PMID- 17549071
TI  - Interleukin-1alpha regulates antimicrobial peptide expression in human
      keratinocytes.
AB  - Human epidermis and epithelium serve as physiologic barriers to protect against
      noxious and infectious agents. Contributing to the defense against infection,
      epithelial cells express antimicrobial peptides (AMPs). The expression of AMPs in
      keratinocytes is generally regulated directly by bacteria and indirectly by
      proinflammatory cytokines. Bacteria may also regulate AMP expression by inducing
      keratinocyte expression of the autonomous proinflammatory cytokine, interleukin
      1alpha (IL-1alpha). To test the hypothesis that AMP expression may be regulated
      by cell autonomous cytokines, we investigated the effect of IL-1alpha on the
      expression of AMPs in human keratinocytes (HaCaT cells) by microarray, northern
      blot, reverse transcriptase (RT)-PCR and western blot analyses. IL-1alpha
      increased expression of mRNA in a dose- and time-dependent manner specific for
      lipocalin 2, S100A8, S100A9 and secretory leukocyte protease inhibitor (SLPI)
      more than twofold relative to nonstimulated cells (control), and slightly
      upregulated S100A7 and beta-defensin-2. Furthermore, the expression of lipocalin
      2, S100A7, S100A8, S100A9 and SLPI proteins were upregulated by IL-1alpha. On the
      other hand, HaCaT cells expressed mRNA specific for other AMPs, including
      cystatin 3, adrenomedullin, RNase-7 and mucin 5, which were unaffected by IL
      1alpha treatment. These results suggest that the autonomous keratinocyte
      cytokine, IL-1alpha, selectively upregulates the expression of AMPs which may
      modulate innate epithelial cell immunity in skin and mucosa.

PMID- 17549072
TI  - Optimization of TCR transgenic T cells for in vivo tracking of immune responses.
AB  - T-cell receptor (TCR) transgenic mice have proven useful for the study of various
      immune parameters. Despite this, it has been suggested that transferred T cells
      respond differently to their endogenous counterparts at least in terms of
      conversion to antigen-experienced populations bearing memory cell markers. Here,
      we have compared the response of TCR transgenic T cells to endogenous populations
      within the context of infection with herpes simplex virus. We found that adoptive
      transfer at numbers approaching those of the endogenous virus-specific subset
      results in a response with similar kinetics, magnitude and memory subset
      conversion. This suggests that this form of optimized T-cell transfer remains a
      useful means of tracking antiviral immune responses.

PMID- 17549073
TI  - Bid activation during induction of extrinsic and intrinsic apoptosis in
      eosinophils.
AB  - Eosinophils readily undergo apoptosis when removed from a physiological
      environment via activation of the intrinsic cell death pathway. This can be
      further enhanced by certain chemicals (for example, glucocorticoid), or by
      extrinsic means (that is, Fas receptor engagement). In this investigation, we
      examined the relative importance of these pathways in cultured human peripheral
      blood eosinophils in the context of expression and activation of the BH3-only
      Bcl2 homologue Bid. Bid activation was examined under conditions where programmed
      cell death was either stimulated (via Fas engagement or glucocorticoid treatment)
      or inhibited (interleukin-5 (IL-5)) relative to control. Full-length Bid was
      found to be highly expressed in eosinophils, and processed to a similar extent
      during either agonist anti-Fas or glucocorticoid treatment. IL-5 blocked
      intrinsic Bid activation during factor withdrawal or glucocorticoid treatment,
      and partially attenuated that caused by Fas activation. Caspase 8 (but not
      caspase 9) antagonism partly but significantly affected receptor-mediated Bid
      activation and cell death; these processes were not altered by either caspase
      inhibitor during simple factor withdrawal or glucocorticoid treatment. Bid
      processing appears to be central to both intrinsic and extrinsic pathways of cell
      death in eosinophils. The role of IL-5 in blocking the intrinsic pathway of
      eosinophil apoptosis is underscored. Results of specific inhibition support the
      existence of Bid activation pathways in eosinophils other than those mediated by
      the classic initiator caspases.

PMID- 17549074
TI  - T-cell sensitivity: a microRNA regulates the sensitivity of the T-cell receptor.

PMID- 17549075
TI  - A brief history of sciatica.
AB  - STUDY DESIGN: Historical review. OBJECTIVES: Appraise history of concept of
      sciatica. SETTING: Europe. METHODS: Selected, original quotations and a
      historical review. RESULTS: Evolution of ideas from hip disorders, through
      interstitial neuritis. CONCLUSION: Current concepts of discogenic sciatica.

PMID- 17549076
TI  - New data, please.
AB  - Meetings and conferences are the best places to feature the latest results coming
      out of the laboratory. Unfortunately, not enough researchers take advantage of
      these opportunities.

PMID- 17549077
TI  - Protein structure space is much more than the sum of its folds.

PMID- 17549078
TI  - Protein Structure Initiative: getting into gear.
AB  - The Protein Structure Initiative of the US National Institutes of Health has
      entered its second year. Its status is reported here, as discussed at December's
      meeting of the principal investigators.

PMID- 17549079
TI  - RAD51, BRCA2 and DNA repair: a partial resolution.

PMID- 17549080
TI  - It takes more than two to tango: Dishevelled polymerization and Wnt signaling.

PMID- 17549081
TI  - Moving parts: how the adaptor protein CRK is regulated, and regulates.

PMID- 17549086
TI  - Defining the appropriate measure of success for adjuvant radiation following
      prostatectomy.

PMID- 17549087
TI  - Does the Health Assessment Questionnaire predict 5-year quality of life in early
      RA?

PMID- 17549088
TI  - Is risedronate or alendronate more effective at preventing nonvertebral fractures
      in women with osteoporosis?

PMID- 17549089
TI  - Partial breast irradiation using targeted intraoperative radiotherapy (Targit).

PMID- 17549090
TI  - Does addition of lapatinib to capecitabine improve outcome in women with
      refractory breast cancer?

PMID- 17549091
TI  - Defined weight expectations in overweight women: anthropometrical, psychological
      and eating behavioral correlates.
AB  - OBJECTIVE: To examine associations between defined weight expectations and
      anthropometric profile and to identify psychological and eating behavioral
      factors that characterize women having more realistic weight expectations.
      METHODS: A nonrandom sample of 154 overweight/obese women completed the 'Goals
      and Relative Weight Questionnaire', which assessed four weight expectations: (1)
      dream weight (whatever wanted to weight); (2) happy weight (would be happy to
      achieve); (3) acceptable weight (could accept even if not happy with it); and (4)
      disappointed weight (would not view as a successful achievement). Psychological
      assessments evaluated dysphoria, self-esteem, satisfaction with one's body (i.e.,
      body esteem) and weight-related quality of life. The 'Three-Factor Eating
      Questionnaire' assessed eating behaviors: (1) cognitive dietary restraint
      (control of food intake), (2) disinhibition (overconsumption of food with a loss
      of control), and (3) susceptibility to hunger (food intake in response to
      feelings and perceptions of hunger). RESULTS: Women's expectations for their
      dream (60.6+/-6.0 kg), happy (65.2+/-6.4 kg) and acceptable (67.9+/-6.8 kg)
      weights corresponded to higher percentages of weight loss (24.2+/-6.6% or 19.8+/
      7.1 kg, 18.6+/-5.8% or 15.2+/-6.0 kg and 15.2+/-5.7% or 12.6+/-5.8 kg,
      respectively) than goals recommended for overweight individuals. Defined weight
      expectations were positively associated with current weight and body mass index
      (BMI; 0.37 < or = r < or = 0.85; P<0.0001). When women were matched one by one
      for their current BMI, but showing different happy BMI, women with a more
      realistic happy BMI were older (P=0.03) and were characterized by a greater
      satisfaction towards body weight (P=0.04), a higher score for flexible restraint
      (P=0.003) and a lower score for susceptibility to hunger (P=0.02) than women with
      a less realistic happy BMI. CONCLUSION: These findings suggest that having more
      realistic weight expectations is related to healthier psychological and eating
      behavioral characteristics.

PMID- 17549092
TI  - BMI, fat mass, abdominal adiposity and visceral fat: where is the 'beef'?

PMID- 17549093
TI  - Disrupted sleep in patients with IBS--a wake-up call for further research?

PMID- 17549094
TI  - Can self-monitoring of foot temperature help prevent recurrence of diabetic foot
      ulcers?

PMID- 17549095
TI  - Does addition of vildagliptin to metformin monotherapy improve glycemic control
      in patients with type 2 diabetes mellitus?

PMID- 17549096
TI  - REMEDIAL: a role for sodium bicarbonate in the prevention of contrast-induced
      nephropathy.

PMID- 17549097
TI  - Is weekend hospital admission associated with increased mortality in patients
      with acute myocardial infarction?

PMID- 17549099
TI  - A worthy experience for a chiropractor.

PMID- 17549098
TI  - Catheter ablation of accessory pathways: is remote control viable?

PMID- 17549100
TI  - Canadian chiropractic researchers: Dr. Greg Kawchuk.

PMID- 17549102
TI  - Canadian chiropractic researchers: Dr. Ted Crowther.

PMID- 17549101
TI  - Canadian chiropractic researchers: Dre Karine Boily.

PMID- 17549103
TI  - Low-tech rehabilitation of bilateral patellofemoral knee pain in a runner: a case
      study.
AB  - Patellofemoral pain is a common ailment within both the running and general
      populations. Many of the structures of the anterior knee that comprise the
      patellofemoral joint can be the source of chronic pain and inflammation that is
      associated with this condition. Much of the evidence in the literature points to
      a delay in activation of the vastus medialis oblique muscle as compared to the
      vastus lateralis, vastus medialis weakness, and ultimately faulty patellar
      tracking as the chief causative factors in the development of patellofemoral
      pain. This is a single case study of a 51-year-old recreational runner with an 18
      month history of bilateral patellofemoral knee pain. Treatment included the use
      of low-tech in office rehabilitation strategies known to affect those causative
      factors responsible for patellofemoral pain. Evidence based treatment modalities
      were utilized in combination, which included patellar mobilization, spinal
      manipulation, proprioceptive and strength training, and semi-rigid orthotic use,
      to effect vastus medialis oblique vs. vastus lateralis activation, vastus
      medialis strength, and patellar movement. The patient responded very well to a 12
      week course of treatment and resumed recreational running with minimal to no pain
      at the six month, one and two year follow-ups.

PMID- 17549104
TI  - Oral squamous cell carcinoma: an atypical presentation mimicking
      temporomandibular joint disorder.
AB  - A 50-year-old female presented to a chiropractic clinic with left jaw pain
      consistent with temporomandibular joint disorder. Examination revealed a large
      ulcerated mass on the posterolateral margin of the tongue which was later
      diagnosed as squamous cell carcinoma. Squamous cell carcinoma is the most common
      of the oral cancers. These cancers are often detected late making treatment more
      complicated and reducing the chance of survival. In the early stages squamous
      cell carcinoma can be asymptomatic. Symptoms can be similar to that of
      temporomandibular joint disorder making examination of the patient's mouth
      important to rule out oral cancers. Oral cancers should be considered when
      patients present to a chiropractor with pain in the area of the temporomandibular
      joint. Risk factors such as chronic tobacco and alcohol use should raise concern
      in these patients. Suspicious lesions should be referred immediately for further
      investigation.

PMID- 17549106
TI  - Canadian chiropractic research bulletin #9.

PMID- 17549105
TI  - Comparison of a triaxial fluxgate magnetometer and Toftness sensometer for body
      surface EMF measurement.
AB  - INTRODUCTION: The use of magnetic fields to treat disease has intrigued mankind
      since the time of the ancient Greeks. More recently it has been shown that
      electromagnetic field (EMF) treatment aids bone healing, and repetitive
      transcranial magnetic stimulation (rTMS) appears to be beneficial in treating
      schizophrenia and depression. Since external EMFs influence internal body
      processes, we hypothesized that measurement of body surface EMFs might be used to
      detect disease states and direct the course of subsequent therapy. However,
      measurement of minute body surface EMFs requires use of a sensitive and well
      documented magnetometer. In this study we evaluated the sensitivity and frequency
      response of a fluxgate magnetometer with a triaxial probe for use in detecting
      body surface EMF and we compared the magnetometer readings with a signal from a
      Toftness Sensometer, operated by an experienced clinician, in the laboratory and
      in a clinical setting. METHODS: A Peavy Audio Amplifier and variable power output
      Telulex signal generator were used to develop 50 microT EMFs in a three coil
      Merritt coil system. A calibrated magnetometer was used to set a 60 Hz 50 microT
      field in the coil and an ammeter was used to measure the current required to
      develop the 50 microT field. At frequencies other than 60 Hz, the field strength
      was maintained at 50 microT by adjusting the Telulex signal output to keep the
      current constant. The field generated was monitored using a 10 turn coil
      connected to an oscilloscope. The oscilloscope reading indicated that the field
      strength was the same at all frequencies tested. To determine if there was a
      correspondence between the signals detected by a fluxgate magnetometer (FGM1) and
      the Toftness Sensometer both devices were placed in the Merritt coil and readings
      were recorded from the FGM1 and compared with the ability of a highly experienced
      Toftness operator to detect the 50 microT field. Subsequently, in a clinical
      setting, FGM1 readings made by an FGM1 technician and Sensometer readings were
      made by 4 Toftness Sensometer operators, having various degrees of experience
      with this device. Each examiner obtained instrument readings from 5 different
      volunteers in separate chiropractic adjusting rooms. Additionally, one of the
      Toftness Sensometers was equipped with an integrated fluxgate magnetometer (FGM2)
      and this magnetometer was used to obtain a second set of EMF readings in the
      clinical setting. RESULTS: The triaxial fluxgate magnetometer was determined to
      be moderately responsive to changes in magnetic field frequency below 10 Hz. At
      frequencies above 10 Hz the readings corresponded to that of the ambient static
      geofield. The practitioner operating the Toftness Sensometer was unable to detect
      magnetic fields at high frequencies (above 10 Hz) even at very high EMFs. The
      fluxgate magnetometer was shown to be essentially a DC/static magnetic field
      detector and like all such devices it has a limited frequency range with some low
      level of sensitivity at very low field frequencies. The interexaminer reliability
      of four Toftness practitioners using the Sensometer on 5 patients showed low to
      moderate correlation. CONCLUSIONS: The fluxgate magnetometer although highly
      sensitive to static (DC) EMFs has only limited sensitivity to EMFs in the range
      of 1 to 10 Hz and is very insensitive to frequencies above 10 Hz. In laboratory
      comparisons of the Sensometer and the fluxgate magnetometer there was an
      occasional correspondence between the two instruments in detecting magnetic
      fields within the Merritt coil but these occasions were not reproducible. In the
      clinical studies there was low to moderate agreement between the clinicians using
      the Sensometer to diagnosing spinal conditions and there was little if any
      agreement between the Sensometer and the fluxgate magnetometer in detecting EMFs
      emanating from the volunteers body surface.

PMID- 17549107
TI  - Tips for writing a successful CIHR Grant Application or Request for Renewal.

PMID- 17549108
TI  - Does chiropractic "add years to life"?

PMID- 17549109
TI  - Does chiropractic "add years to life"?

PMID- 17549110
TI  - Does chiropractic "add years to life"?

PMID- 17549111
TI  - Chiropractic dinosaur.

PMID- 17549112
TI  - The effect of low force chiropractic adjustments on body surface electromagnetic
      field.

PMID- 17549113
TI  - Canadian chiropractic researchers: Dr. Doug Lawson.

PMID- 17549115
TI  - Canadian Chiropractic Research Foundation: Dr. Rob Allaby.

PMID- 17549114
TI  - Canadian chiropractic researchers: Dr. Jean-Sebastien Blouin.

PMID- 17549116
TI  - Policy trumps science in the Bush administration.

PMID- 17549117
TI  - Chiropractic dinosaur.

PMID- 17549118
TI  - Sternocleidomastoid syndrome: a case study.
AB  - This article presents a case study of a patient diagnosed with dysfunction of the
      sternocleidomastoid (SCM) muscle, a condition which can result in head and face
      pain, nausea, dizziness, coryza, and lacrimation. In this particular case, the
      SCM muscle had developed tightness and weakness with presence of multiple trigger
      points within both heads. A combination of passive and active treatments were
      utilized to successfully treat this condition.

PMID- 17549119
TI  - Identification of internal carotid artery dissection in chiropractic practice.
AB  - Internal carotid artery dissection (ICAD) is a condition involving separation of
      the artery's intimal lining from its medial division, with subsequent extension
      of the dissection along varying distances of the artery, usually in the direction
      of blood flow. ICAD may produce cerebral ischemia due to occlusion of the
      involved artery. This occlusion may occur at or near the site of the dissection,
      or "downstream" as a result of embolization from a dislodged thrombus fragment.
      The problem any chiropractic physician faces in identifying ICAD patients is that
      the condition may present without any symptoms or the symptoms may appear benign
      (e.g., headache, neck pain or cervicogenic dizziness). Consequently, it may be
      impossible to identify some ICAD patients, especially in the early stages of the
      pathology. As the ICAD progresses and neural blood flow is compromised, the
      symptom picture typically manifests more completely. The chiropractic physician
      must be alert to characteristic findings of a progressing ICAD, since an
      immediate referral to a medical specialist may be required.

PMID- 17549120
TI  - Intermittent axial wrist traction as a conservative treatment for carpal tunnel
      syndrome: a case series.
AB  - Four patients with clinical and electrodiagnostic evidence of carpal tunnel
      syndrome underwent intermittent axial wrist traction with a pneumatic device
      which applied a controlled traction force of forty to sixty pounds per square
      inch along the axis of the forearm. Traction cycled intermittently five seconds
      on and five seconds off. Treatment duration was five minutes. Patients in this
      study received between five and twelve treatment sessions over a three month
      period. All neurophysiological tests were performed at an independent site
      without knowledge of treatment plan before treatment commenced and then repeated
      after the last treatment three months later. Clinical tests were performed
      initially, after three months and after one year. Significant subjective
      improvement in all cases were accompanied by objective improvement and
      normalization of the nerve conduction studies.

PMID- 17549121
TI  - Does chiropractic 'add years to life'?
AB  - The chiropractic cliche "Chiropractic Adds Life to Years and Years to Life" was
      examined for validity. It was assumed that chiropractors themselves would be the
      best informed about the health benefits of chiropractic care. Chiropractors would
      therefore be most likely to receive some level of chiropractic care, and do so on
      a long-term basis. If chiropractic care significantly improves general health
      then chiropractors themselves should demonstrate longer life spans than the
      general population. Two separate data sources were used to examine chiropractic
      mortality rates. One source used obituary notices from past issues of Dynamic
      Chiropractic from 1990 to mid-2003. The second source used biographies from Who
      Was Who in Chiropractic - A Necrology covering a ten year period from 1969-1979.
      The two sources yielded a mean age at death for chiropractors of 73.4 and 74.2
      years respectively. The mean ages at death of chiropractors is below the national
      average of 76.9 years and is below their medical doctor counterparts of 81.5.This
      review of mortality date found no evidence to support the claim that chiropractic
      care "Adds Years to Life."

PMID- 17549122
TI  - The use of non-amplitude components of the myoelectric signal in identifying
      differences in function between the low back injured and controls.
AB  - This article primarily reviews the assessment of the non-amplitude dependent
      components of the myoelectric signal in assessing lumbar function in the low back
      injured and how persons with low back injuries may differ from the non-injured.
      Assessment of anomalies in function can loosely be categorized into 4 separate
      protocols: 1. Assessing the pattern of myoelectric activation, 2. Assessing the
      EMG frequency spectrum during fatigue, 3. Assessing EMG onset timing during
      movement and stability challenges and 4. Assessing myoelectric function with link
      segment models and EMG assisted spinal models. Assessing the EMG spectrum during
      fatigue can discriminate between populations; however, questions regarding across
      day repeatability limit its ability to identify change over time. The remaining
      techniques are relatively new, show statistically significant differences between
      the low back injured and normals and provide insight into aberrant spinal
      stability, motor control function and spinal loading. Their response to
      rehabilitation programs is largely unknown suggesting a need and avenue for
      future research.

PMID- 17549123
TI  - The effect of low force chiropractic adjustments on body surface electromagnetic
      field.

PMID- 17549125
TI  - Commentary: Orthopaedics and chiropractic, a close relationship.

PMID- 17549124
TI  - Orthopaedics and chiropractic -a close relationship.

PMID- 17549126
TI  - Does an audible release improve the outcome of a chiropractic adjustment?

PMID- 17549127
TI  - Is chiropractic a CAM therapy or is it a separate profession?

PMID- 17549128
TI  - Are you listening?

PMID- 17549129
TI  - Open access publication is growing in importance.

PMID- 17549130
TI  - Another chiropractic dinosaur.

PMID- 17549133
TI  - Complementarity and synergy: the Canadian and US approaches to supporting the
      knowledge needs...of a self-determining chiropractic profession.

PMID- 17549135
TI  - [Motion palpation].
AB  - BACKGROUND: Motion palpation has been used as a diagnostic tool for vertebral
      subluxation, even though its reliability is questionable. Standardisation of
      palpation has proven substantially more reliable. A scale of assessment of a
      standardized palpation has not yet been tested for reliability. OBJECTIVE: The
      measure of intraexaminer and interexaminer reliability of a scale of assessment
      for the standardized palpation of cervical rotation. DESIGN: Intraexaminer study:
      Twelve chiropractic students were assessed by a blindfolded experienced
      clinician. Interexaminer study: Twelve regular patients with a history of neck
      problem were assessed by two chiropractors in a clinical setting. RESULTS: Data
      analysis shows fair to strong reliability (k = 0.34 and 0.65) for the scale of
      assessment that was used. The results are comparable to other assessment scales
      used currently in practice. CONCLUSION: The utilisation of a scale of assessment
      for standardised motion palpation may prove a useful clinical tool, as other
      common testing measures (tendon reflex, muscle tone, muscle strength) which use
      similar scale of assessment.

PMID- 17549136
TI  - Cervical collars and braces in athletic brachial plexus injury and excessive
      cervical motion prevention: a review of the literature.
AB  - A review of the literature was conducted to find publications relating to neck
      collars / rolls and prevention of sports injury, particularly burners and other
      cervical spine injuries, as well as in preventing excessive motion of the
      cervical spine. MEDLINE (1970-2005), Cinahl (1982-2005), Alt Health Watch (1990
      2005), AMED (1995-2005), and the Index to Chiropractic Literature (1985-2005)
      databases were searched. To date there has been very little documented study into
      the ability of cervical collars/neck rolls to prevent excessive motion of the
      cervical spine or to prevent injury. Neck rolls/braces are capable of limiting
      cervical hyperextension under laboratory conditions, but the same can not be said
      for their ability to limit lateral flexion. Only one empirical study could be
      identified that looked at the ability of a collar to prevent burners and other
      neck injuries in athletes. Further laboratory and on-field studies are clearly
      needed.

PMID- 17549134
TI  - Chiropractic clinical practice guideline: evidence-based treatment of adult neck
      pain not due to whiplash.
AB  - OBJECTIVE: To provide an evidence-based clinical practice guideline for the
      chiropractic cervical treatment of adults with acute or chronic neck pain not due
      to whiplash. This is a considerable health concern considered to be a priority by
      stakeholders, and about which the scientific information was poorly organized.
      OPTIONS: Cervical treatments: manipulation, mobilization, ischemic pressure,
      clinic- and home-based exercise, traction, education, low-power laser, massage,
      transcutaneous electrical nerve stimulation, pillows, pulsed electromagnetic
      therapy, and ultrasound. OUTCOMES: The primary outcomes considered were improved
      (reduced and less intrusive) pain and improved (increased and easier) ranges of
      motion (ROM) of the adult cervical spine. EVIDENCE: An "extraction" team recorded
      evidence from articles found by literature search teams using 4 separate
      literature searches, and rated it using a Table adapted from the Oxford Centre
      for Evidence-based Medicine. The searches were 1) Treatment; August, 2003, using
      MEDLINE, CINAHL, AMED, MANTIS, ICL, The Cochrane Library (includes CENTRAL), and
      EBSCO, identified 182 articles. 2) Risk management (adverse events); October,
      2004, identified 230 articles and 2 texts. 3) Risk management (dissection);
      September, 2003, identified 79 articles. 4) Treatment update; a repeat of the
      treatment search for articles published between September, 2003 and November,
      2004 inclusive identified 121 articles. VALUES: To enable the search of the
      literature, the authors (Guidelines Development Committee [GDC]) regarded
      chiropractic treatment as including elements of "conservative" care in the search
      strategies, but not in the consideration of the range of chiropractic practice.
      Also, knowledge based only on clinical experience was considered less valid and
      reliable than good-caliber evidence, but where the caliber of the relevant
      evidence was low or it was non-existent, unpublished clinical experience was
      considered to be equivalent to, or better than the published evidence. REPORTED
      BENEFITS, HARMS AND COSTS: The expected benefits from the recommendations include
      more rapid recovery from pain, impairment and disability (improved pain and ROM).
      The GDC identified evidence-based pain benefits from 10 unimodal treatments and
      more than 7 multimodal treatments. There were no pain benefits from magnets in
      necklaces, education or relaxation alone, occipital release alone, or head
      retraction-extension exercise combinations alone. The specificity of the studied
      treatments meant few studies could be generalized to more than a minority of
      patients. Adverse events were not addressed in most studies, but where they were,
      there were none or they were minor. The theoretic harm of vertebral artery
      dissection (VAD) was not reported, but an analysis suggested that 1 VAD may occur
      subsequent to 1 million cervical manipulations. Costs were not analyzed in this
      guideline, but it is the understanding of the GDC that recommendations limiting
      ineffective care and promoting a more rapid return of patients to full functional
      capacity will reduce patient costs, as well as increase patient safety and
      satisfaction. For simplicity, this version of the guideline includes primarily
      data synthesized across studies (evidence syntheses), whereas the technical and
      the interactive versions of this guideline (http://ccachiro.org/cpg) also include
      relevant data from individual studies (evidence extractions). RECOMMENDATIONS:
      The GDC developed treatment, risk-management and research recommendations using
      the available evidence. Treatment recommendations addressing 13 treatment
      modalities revolved around a decision algorithm comprising diagnosis (or
      assessment leading to diagnosis), treatment and reassessment. Several specific
      variations of modalities of treatment were not recommended. For adverse events
      not associated with a treatment modality, but that occur in the clinical setting,
      there was evidence to recommend reconsideration of treatment options or referral
      to the appropriate health services. For adverse events associated with a
      treatment modality, but not a known or observable risk factor, there was evidence
      to recommend heightened vigilance when a relevant treatment is planned or
      administered. For adverse events associated with a treatment modality and
      predicted by an observable risk factor, there was evidence to recommend absolute
      contraindications, and requirements for treatment modality modification or
      caution to minimize harm and maximize benefit. For managing the theoretic risk of
      dissection, there was evidence to recommend a systematic risk-management
      approach. For managing the theoretic risk of stroke, there was support to
      recommend minimal rotation in administering any modality of upper-cervical spine
      treatment, and to recommend caution in treating a patient with
      hyperhomocysteinemia, although the evidence was especially ambiguous in both of
      these areas. Research recommendations addressed the poor caliber of many of the
      studies; the GDC concluded that the scientific base for chiropractic cervical
      treatment of neck pain was not of sufficient quality or scope to "cover" current
      chiropractic practice comprehensively, although this should not suggest other
      disciplines are more evidence-based. VALIDATION: This guideline was authored by
      the 10 members of the GDC (Elizabeth Anderson-Peacock, Jean-Sebastien Blouin,
      Roland Bryans, Normand Danis, Andrea Furlan, Henri Marcoux, Brock Potter, Rick
      Ruegg, Janice Gross Stein, Eleanor White) based on the work of 3 literature
      search teams and an evidence extraction team, and in light of feedback from a
      commentator (Donald R Murphy), a 5-person review panel (Robert R Burton, Andrea
      Furlan, Richard Roy, Steven Silk, Roy Till), a 6-person Task Force (Grayden
      Bridge, H James Duncan, Wanda Lee MacPhee, Bruce Squires, Greg Stewart, Dean
      Wright), and 2 national profession-wide critiques of complete drafts. Two
      professional editors with extensive guidelines experience were contracted (Thor
      Eglington, Bruce P Squires). Key contributors to the guideline included
      individuals with specialties or expert knowledge in chiropractic, medicine,
      research processes, literature analysis processes, clinical practice guideline
      processes, protective association affairs, regulatory affairs, and the public
      interest. This guideline has been formally peer reviewed.

PMID- 17549137
TI  - Re: Characterization of side effects sustained by chiropractic students during
      their undergraduate training in technique class at a chiropractic college: a
      preliminary retrospective study.

PMID- 17549138
TI  - Re: Characterization of side effects sustained by chiropractic students during
      their undergraduate training in technique class at a chiropractic college: a
      preliminary retrospective study.

PMID- 17549140
TI  - Re: Characterization of side effects sustained by chiropractic students during
      their undergraduate training in technique class at a chiropractic college: a
      preliminary retrospective study.

PMID- 17549144
TI  - Dr. Deborah Kopansky-Giles, DC, FCCS(C), FICC.

PMID- 17549142
TI  - Report on the Conference on the Biology of Manual Therapies: a historic
      collaboration between the Canadian Institutes of Health Research and the United
      States National Institutes of Health.

PMID- 17549146
TI  - Chiropractors struggle with change.

PMID- 17549145
TI  - Dr. Justin Marcotte, DC, MSc.

PMID- 17549147
TI  - How Chiropractors began working in a Community Health Centre in Ottawa.

PMID- 17549148
TI  - Practice patterns of 692 Ontario chiropractors (2000-2001).
AB  - This study examined a wide range of variables relating to the practice patterns
      of 692 Ontario chiropractors (approximately 30% of all registrants in the
      province) who subscribed to the Ontario Chiropractic Association's Patient
      Management Program. It analyzed the 2000-2001 data of these chiropractors and
      provided important information on such factors as practitioner and patient
      demographics, practice profiles, and reimbursement patterns.The mean number of
      chiropractic treatments per patient for the year was 8.6 (sd = 3.4) and the mean
      treatment fee (above OHIP) per patient visit was $17.60 (sd = 5.0). Nearly one
      third of patient treatments were for lumbar complaints, and more than one-third
      of the patients were between 35 and 50 years of age.The mean annual gross income
      of the chiropractors in this study was $148,824 (sd = $86,391), with the male
      practitioners having a statistically significantly higher mean income ($161,363)
      than their female counterparts ($108,126). Practice location was significantly
      related to income, with postal code 'M' (Toronto) having the lowest mean income
      level. The overwhelming majority of practitioners (85%) used Diversified
      Technique as their primary treatment procedure, while 'modalities' was the most
      commonly selected adjunctive treatment procedure (29%).This study sheds new light
      on the associations among such factors as practitioner gender, practice location,
      and level of income.

PMID- 17549149
TI  - Knowledge and application of correct car seat head restraint usage among
      chiropractic college interns: a cross-sectional study.
AB  - SUMMARY OF BACKGROUND DATA: Cervical spine injuries sustained in rear-end crashes
      cost at least $7 billion in insurance claims annually in the United States alone.
      When positioned correctly, head restraint systems have been proven effective in
      reducing the risk of whiplash associated disorders. Chiropractors should be
      knowledgeable about the correct use of head restraint systems to educate their
      patients and thereby prevent or minimize such injuries. OBJECTIVES: The primary
      objective of this study was to determine the prevalence of correct positioning of
      car seat head restraints among the interns at our institution. The secondary
      objective was to determine the same chiropractic interns' knowledge of the
      correct positioning of car seat head restraints. It was hypothesized that 100
      percent of interns would have their head restraint correctly positioned within an
      acceptable range and that all interns would possess the knowledge to instruct
      patients in the correct positioning of head restraints. STUDY DESIGN: Cross
      sectional study of a convenient sample of 30 chiropractic interns from one
      institution. METHODS: Interns driving into the parking lot of our health center
      were asked to volunteer to have measurements taken and to complete a survey.
      Vertical and horizontal positions of the head restraint were measured using a
      beam compass. A survey was administered to determine knowledge of correct head
      restraint position. The results were recorded, entered into a spreadsheet, and
      analyzed. RESULTS: 13.3 percent of subjects knew the recommended vertical
      distance and only 20 percent of subjects knew the recommended horizontal
      distance. Chi Square analyses substantiated that the majority of subjects were
      unaware of guidelines set forth by the National Highway Traffic Safety
      Administration (NHTSA) for the correct positioning of the head restraint (chi(2)
      (vertical) = 16.13, chi(2) (horizontal) = 10.80, p <.05). Only 6.7 percent of the
      subjects positioned their head restraint at the vertical distance of 6 cm or less
      (p <.05). However, 60 percent of the subjects positioned their head restraint at
      the recommended horizontal distance of 7 cm or less, but this was no different
      than could be expected by chance alone (p >.05). Interestingly, the 13.3 percent
      of the subjects who were aware of the vertical plane recommendations did not
      correctly position their own head restraint in the vertical plane. Similarly,
      only half of the subjects who were aware of the horizontal plane recommendations
      correctly positioned their head restraint in the horizontal plane. The data
      suggest that chance alone could account for the correct positioning of the head
      restraint in our subjects. CONCLUSIONS: The results of this cross-sectional study
      raise concerns about chiropractic intern knowledge and application of correct
      head restraint positioning. The importance of chiropractors informing patients of
      the correct head restraint position should be emphasized in chiropractic
      education to help minimize or prevent injury in patients involved in motor
      vehicle collisions.

PMID- 17549150
TI  - Ulnar nerve neuropraxia after extracorporeal shock wave lithotripsy: a case
      report.
AB  - A case is presented that illustrates and discusses the clinical presentation,
      diagnosis and chiropractic management of a 50-year-old male presenting with a
      case of ulnar neuropraxia following extracorporal shockwave lithotripsy. Onset is
      believed to be due to the patient's arm position in full abduction and external
      rotation during the lithotripsy procedure. Motor abnormalities related to the
      ulnar nerve were noted in the absence of distinct sensory findings. Chiropractic
      treatment focused on relief of the patient's pain during the course of the
      condition. Treatment may have helped in the rapid and complete resolution of his
      symptoms in this case. Poor patient positioning on hard surfaces, for extended
      periods may place pressure on superficial nerves resulting in nerve injury. In
      this case, the outcome was excellent, with complete resolution of symptoms less
      than one week later. The prognosis for this type of neuropraxia is usually good
      with conservative management. The patient history and chronological clinical
      course strongly suggest a causal association between the patient's position
      during the procedure and the development of the ulnar neuropraxia.

PMID- 17549152
TI  - Systematic reviews help users keep up with expanding volume of research evidence.

PMID- 17549151
TI  - Characterization of side effects sustained by chiropractic students during their
      undergraduate training in technique class at a chiropractic college: a
      preliminary retrospective study.
AB  - INTRODUCTION: The purpose of this study was to characterize the type, nature and
      frequency of injuries sustained by chiropractic students during their
      undergraduate training. METHODS: Chiropractic students in their second, third and
      fourth year of study at a chiropractic college were asked to complete a
      questionnaire that chronicled and described the occurrence of any side effects
      they may have sustained at the hands of their peers during technique class.
      Students were also asked to record their anthropomorphic characteristic. RESULTS:
      Of 450 questionnaires distributed, 292 were completed and returned to the
      authors. Of the 292 respondents, 127 reported to have experienced an injury,
      although the total number of injuries was 161. The most common site of injury was
      the lumbopelvic region. Students reported that it was during their second year of
      study that they experienced the highest number of injuries. Symptoms occurred the
      same day as the event in 85% of cases. The most common characteristic of symptoms
      reported was pain, followed by local stiffness, headache, dizziness, fatigue,
      diffuse stiffness and cramps. Two thirds of students described the extent of
      their injuries from 'light' to 'a fair bit'. Three quarters of injuries resolved
      within the first 72 hours of the event. No treatment was sought by 89 (55%) of
      the respondents. More than half of students reported that their activities of
      daily living were either 'not' or 'somewhat' affected. There were three reports
      of long-term complaints. No statistically significant differences were found
      between the group of students reporting to be injured compared to those students
      not injured with respect to their age, gender, weight or height. CONCLUSION:
      Chiropractic students experience side effects during their undergraduate training
      that are very similar to those experienced by patients under clinical care.

PMID- 17549153
TI  - Use of fallacious arguments, Ad Hominem attacks, and biased 'expert opinions' can
      make CBP research 'appear flawed'.

PMID- 17549154
TI  - A rebuttal to chiropractic radiologists' view of the 50-year-old, linear-no
      threshold radiation risk model.

PMID- 17549155
TI  - Lateral epicondylosis: a case study of conservative care utilizing ART and
      rehabilitation.
AB  - OBJECTIVE: To present the diagnostic features of lateral epicondylosis and
      response to treatment by Active Release Technique (ART), a promising treatment
      for lateral epicondylosis. CLINICAL FEATURES: The most important feature is pain
      at the lateral epicondyle of the humerus, most notably in actively extending or
      passively flexing the wrist. INTERVENTION AND OUTCOME: Treatment involves
      eliminating any inflammation, reducing muscular pain and hypertonicity,
      correcting biomechanical dysfunction, and restricting/modifying the offending
      activity. ART was successfully utilized in an attempt to remove adhesions and
      promote restoration of normal tissue texture. A sports specific rehabilitation
      protocol was employed to re-establish wrist extensor strength and interferential
      current and ice were used to control pain and residual inflammation. CONCLUSION:
      A combination of soft tissue therapy, rehabilitation, and therapeutic modalities
      is a protocol that may be used by both allopathic and chiropractic practitioners
      alike, and allow for the athletic patient to return to play as quickly as
      possible.

PMID- 17549156
TI  - The Bournemouth Questionnaire as an outcome measure in the rehabilitation of a
      person suffering with mechanical neck and arm pain and concurrent Charcot-Marie
      Tooth disease: a case report.
AB  - OBJECTIVE: The objective of this paper was to present a report in which the
      Bournemouth Questionnaire was used as an outcome measure in the treatment and
      rehabilitation of an individual previously diagnosed with Charcot-Marie-Tooth
      disease and concurrently suffering with mechanical neck and arm pain. DESIGN
      ARCHITECTURE: This was a retrospective case report. SAMPLE PROFILE: An individual
      over 18 years of age previously diagnosed with Charcot-Marie-Tooth disease and
      now suffering with mechanical neck and arm pain. The individual is free from
      other illnesses and the individual is free from contra-indications to
      chiropractic care and rehabilitation. OUTCOME MEASURES: The outcome measures of
      this case report were based on the Bournemouth Neck Questionnaire. METHOD: The
      course of treatment involved diversified chiropractic manipulative therapy of
      involved joints, soft tissue therapy and specific rehabilitative postural
      exercises. Outcome measures were compared to pretreatment baselines. The
      Bournemouth Neck Questionnaire was completed at weeks 0, and 6. The length of the
      study was 6 weeks. Re-evaluation of treatment occurred at similar intervals.
      RESULTS: The Bournemouth patient raw scores pre-intervention were 6, 3, 2, 7, 2,
      4, 2 with a total score of 26/70. Post intervention raw scores were 4, 2, 0, 7,
      1, 2, 1 with a total score of 17/70. The percentage change score was 34.6.
      CONCLUSION: The change in raw scores was not clinically important. The percentage
      change score is considered indicative of clinically important change. The
      following two questions for further study are presented. Can the questions
      relating to depression and mood in the Bournemouth Questionnaire be used as a
      clinical indicator of adherence to home exercise programs? Can the Bournemouth
      Questionnaire be used as an appropriate outcome measure of non-specific
      musculoskeletal pain in individuals suffering from Charcot-Marie-Tooth disease?

PMID- 17549157
TI  - Sports related concussion and spinal injuries: the need for changing spearing
      rules at the National Capital Amateur Football Association (NCAFA).
AB  - INTRODUCTION: Returning an athlete to play following a spinal or concussive
      injury remains a challenge for the health practitioner making the decision. Among
      the possible mechanisms responsible for such injuries in amateur football, the
      concept of "spearing" has attracted a great deal of attention in sport medicine.
      OBJECTIVE: The purpose of this paper is to present a review of the diagnosis and
      treatment of the potentially catastrophic neck and head injuries caused by
      spearing in Canadian amateur football and to suggest the role the chiropractic
      profession can have in their prevention. It proposes to follow the
      recommendations advocated by the National Capital Amateur Football Association
      (NCAFA) athletic trainers group, led by a chiropractor. METHODS: Information
      regarding the concepts and prevention of "spearing", concussion and spinal
      injuries at the amateur football level in both the United States and Canada was
      obtained using the following computerized search methods: PubMed - MeSH (via the
      National Center for Biotechnology Information (NCBI); The Index to Chiropractic
      Literature (ICL); Google Scholar Beta. Recent (2005) information on sports
      related spinal injuries and concussion were obtained by attendance at the 2005
      Sports Related Concussion and Spine Injury Conference. Foxborough, Massachusetts.
      From a total of 698 references, 63 were retained. CONCLUSION: Literature search
      yields very little information regarding Canadian statistics for amateur football
      neck and head injuries. The author encourages such injury data collecting and
      proposes that original Canadian studies and statistical analyses be carried out,
      such as those from diverse sports groups in the United States and abroad.1, 2, 3
      The NCAFA group of trainers recommends a changing of the rules for "spearing"
      within the league and advocates gathering of Canadian based sports injury
      statistics. It also recognizes the need for public presentations (of
      concussion/spinal injuries).5 This paper describes the different interpretations
      of spearing rules at American and Canadian football associations, both at the
      amateur and professional levels; it further shows that injury prevention in
      sports is an absolute necessity and that the chiropractic profession should play
      a role in its application. It is suggested that chiropractors, who often attend
      to athletes who sustained sport related neck and head injuries, ought to
      contribute in their prevention and treatment.

PMID- 17549158
TI  - Defining Quackery: an examination of the Manitoba Medical Profession and the
      early development of professional unity.
AB  - In the early 1920s, the Manitoba medical profession reached a pinnacle in its
      opposition to alternative medicine, waging an aggressive four-year campaign
      against chiropractic and osteopathy to "protect" the public from the dangers of
      alternative forms of healing and prevent "irregulars" from establishing their
      practices. It was during these same years that the Manitoba medical profession
      was able to successfully overcome many internal problems of consensus and
      external problems of legitimacy. Examining the years leading up to, during, and
      following the campaign, this paper demonstrates how the Manitoba medical
      profession's militant reaction to osteopathy and chiropractic during these years
      helped strengthen and differentiate orthodox practitioners as a group, thus
      reinforcing their authority within the public realm.

PMID- 17549159
TI  - Retrospective analysis of laboratory testing at the chiropractic clinic of
      Universite du Quebec a Trois-Rivieres (UQTR).
AB  - This study provides data based on the clinical experience of the Universite du
      Quebec a Trois-Rivieres (UQTR) chiropractic clinic justifying the use of
      laboratory tests in chiropractic practice. The data was gathered retrospectively
      over a 51 month period from January 22, 1997 to April 10, 2001. During this
      period, the UQTR Chiropractic Clinic opened 6571 patient files. The analysis
      reveals that of the 6571 patients, 1200 (18.27%) underwent laboratory processes
      or tests. Of these 1200 processes or tests, 676 (56.34%) showed abnormal
      findings. Of the 676 patients with abnormal findings, 122 (18.05%) cases were
      serious enough to justify a referral to a medical doctor (general practitioner or
      specialist) for immediate follow-up. Among these serious conditions, one was a
      bone neoplastic pathology and one was a case of leukemia. This study emphasizes
      the significant contribution of laboratory tests in chiropractic practice. Its
      importance rests not only with teaching purposes, but also rests with the proper
      assessment of clinical conditions frequently observed in chiropractic practice.
      Laboratory tests used in a proper context serve not only as a valuable instrument
      to identify primary and underlying abnormal physiological factors, but also
      assist the chiropractor in identifying more precisely those cases that require a
      medical referral. This study also demonstrates that laboratory testing of
      chiropractic patients is a necessary and essential clinical procedure for
      complete public protection. It also demonstrates that chiropractors are an
      essential part of the health team even when patients are under medical
      supervision.

PMID- 17549160
TI  - Diagnostic imaging guidelines for the chiropractic profession: a worldwide
      consultation on the web.

PMID- 17549161
TI  - Health is an inside job...

PMID- 17549162
TI  - The Institute of Musculoskeletal Health and Arthritis (IMHA) Knowledge Exchange
      Task Force: an innovative approach to knowledge translation.
AB  - This article will introduce the concept of Knowledge Translation (KT), as defined
      and used by the Canadian Institutes of Health Research (CIHR). The Institute of
      Musculoskeletal Health and Arthritis (IMHA), one of the 13 institutes under the
      umbrella of CIHR, has created the Knowledge Exchange Task Force (KETF) to
      research KT and to determine how to best develop and implement KT initiatives
      within the Canadian research milieu. Task Force goals, objectives and activities
      will be outlined and summarized in poster form. KETF Members, or Research
      Ambassadors, will be recognized, along with the names of their Parent
      Organizations. The paper will detail the process of KT, as defined by CIHR, and a
      promising KT project created by IMHA to build communication pathways between
      scientific researchers, consumers and multiple stakeholders with the ultimate
      goal of improving the quality of life of all Canadians.

PMID- 17549163
TI  - Continuing health education in Canada.

PMID- 17549166
TI  - An unusual presentation and outcome of complex regional pain syndrome: a case
      report.
AB  - A 44 year-old woman presented to a chiropractic clinic with swelling and point
      tenderness over the right metacarpals and right shoulder and elbow pain of
      insidious onset. Examination revealed right wrist and hand swelling, diminished
      grip strength, and reduced wrist and cervical ranges of motion. A bone scan,
      radiographs, and clinical examination led to the diagnosis of complex regional
      pain syndrome (CRPS). Following chiropractic care, the patient had improved grip
      strength, functional abilities, and pain reduction. The primary characteristics
      of CRPS include motor, trophic and sensory changes, usually in a peripheral limb
      following some form of trauma. Due to the varied symptom presentation, it may be
      unclear which conservative therapies will be most beneficial in the treatment of
      CRPS. A multidisciplinary approach to treatment should be pursued with these
      patients. More investigation of therapies such as chiropractic care as it relates
      to the pathophysiology of CRPS is needed.

PMID- 17549167
TI  - Resistance training for performance and injury prevention in golf.
AB  - This introductory resistance training program is designed to minimize injury
      risk, improve golf swing speed and the overall fitness of recreational golfers.
      This article aims to introduce to the Chiropractor the basic concepts sport
      specific resistance training, periodization models of resistance training and
      proposes a year round conditioning resistance training program specific to golf.
      The exercises have been chosen based on the best biomechanical evidence to
      minimize injury risk and on the research supporting the use of movement specific
      training adaptations. Upper body strength exercises are performed standing to
      develop both trunk and hip stabilizing musculature and the primary movement of
      the golf swing.

PMID- 17549168
TI  - The musculoskeletal effects of diabetes mellitus.
AB  - Diabetes mellitus (DM) is a multi-system disease characterized by persistent
      hyperglycemia that has both acute and chronic biochemical and anatomical
      sequelae, with Type-2 DM representing the most common form of the disease.
      Neuromusculoskeletal sequelae of DM are common and the practicing chiropractor
      should be alert to these conditions, as some are manageable in a chiropractic
      office, while others are life and/or limb threatening. This paper reviews the
      effects of DM on the musculoskeletal system so as assist the chiropractor in
      making appropriate clinical decisions regarding therapy, understanding
      contraindications to therapy, referring patients to medical physicians when
      appropriate and understanding the impact that DM may have on the prognosis for
      their patients suffering from the myriad musculoskeletal conditions associated
      with this disease.

PMID- 17549169
TI  - The Homewood influence in Canada and beyond.
AB  - If there is any one individual who stands out in the saga of the early growth and
      development of the Canadian Memorial Chiropractic College, it must be Albert Earl
      Homewood (1916-1990). His contributions included steering the institution through
      the lean 1950s, coping with the metropolitan transit authorities' devastating
      incursion upon the first campus, and arranging the construction and financing of
      the school's second campus. Along the way, this feisty gentleman and respected
      instructor, "chiropractic's Mr. Chips," raised the standard for scholarship among
      DCs and assisted in the administration of several additional chiropractic
      colleges (Lincoln and Los Angeles).

PMID- 17549170
TI  - Re: Is chiropractic a CAM therapy or is it a separate profession?

PMID- 17549171
TI  - Re: Is chiropractic a CAM therapy or is it a separate profession?

PMID- 17549172
TI  - Flawed trials, flawed analysis: why CBP should avoid rating itself.

PMID- 17549173
TI  - Ionizing radiation exposure--more good than harm? The preponderance of evidence
      does not support abandoning current standards and regulations.

PMID- 17549174
TI  - A peer-reviewer's plea.

PMID- 17549176
TI  - Os odontoideum with associated multidirectional atlantoaxial instability: imaging
      and clinical considerations.
AB  - Acquired anomalies of the craniovertebral junction although rare, may result in
      serious clinical sequella. The prevalence of craniovertebral anomalies remains
      unknown since they may remain clinically silent. Os odontoideum is one such
      anomaly. The etiology remains controversial over whether it is a post-traumatic
      or congenital condition but the clinical considerations of os odontoideum remain
      the same. Chiropractors may encounter os odontoideum in the subclinical patient
      with the potential for deleterious effects with manipulation. Radiography is
      essential to its detection.

PMID- 17549177
TI  - Conservative therapy for plantar fasciitis: a narrative review of randomized
      controlled trials.
AB  - A narrative literature review of RCTs only, was conducted to ascertain which
      conservative treatments provide the best results for plantar fasciitis patients.
      Stretching, prefabricated and custom-made orthotics and night splints have all
      been scrutinized in numerous studies with mixed results. Chiropractic
      manipulative therapy has been examined in one study, with favorable results.
      Therapeutic ultrasound and low intensity laser therapy have been examined in one
      study apiece with unsatisfactory results. Based on the trials reviewed a trial of
      therapy beginning with low-cost, patient-centered treatments is recommended,
      particularly stretching, over-the-counter orthotics, and patient education.
      Several (but not all) of the reviewed articles indicated that custom-made
      orthoses are more beneficial for plantar fasciitis than over-the-counter
      orthotics. In the event these treatments do not provide satisfactory results, use
      of night splints should be considered. Based on this review, there is no support
      for the use of magnetic insoles for plantar fasciitis. Most of the studies were
      found to have at least one methodological flaw, including inadequate sample
      sizes, high drop-out rates, comparing multiple interventions to multiple
      interventions (thus making it difficult to determine the effect of each
      individual intervention) and lack of long-term follow-up. Outcome measure use
      between studies was inconsistent.

PMID- 17549178
TI  - Applying structural equation modeling to Canadian Chiropractic Examining Board
      measures.
AB  - The purpose of this research project was to determine if structural equation
      modeling (SEM) can be successfully applied to the Canadian Chiropractic Examining
      Board (CCEB) measures to explore the inferential nature of the "causal"
      relationship between academic ability and success on the CCEB examinations;
      specifically the ability to make correct clinical decisions. As this was a time
      series study (pre-chiropractic grade-point-average to licensure examination
      data), a latent variable path analysis was the SEM method of choice. The
      Comparative Fit Index for the model to data fit was 0.98. Inferences include: 1)
      the need to recruit students with strong academic abilities, 2) the need to hold
      back students who have not achieved a high level of understanding of the first
      two-years of work at chiropractic college, and 3) that the CCEB extended
      matching, long-format questions are a better estimate of clinical reasoning
      ability than 5-option short-format questions or the OSCE.

PMID- 17549179
TI  - A survey of Ontario chiropractors: their views on maximizing patient compliance
      to prescribed home exercise.
AB  - OBJECTIVE: The objective of this study was to compile an inventory of the
      strategies most frequently used by Ontario chiropractors in their efforts to
      maximize patient compliance to prescribed home exercise. DESIGN: The design
      consisted of a cross-sectional self-report web-based survey of Ontario
      chiropractors. PARTICIPANTS: Eligible participants consisted of chiropractors in
      active practice in Ontario (treating, on average, at least 1 patient per week)
      and prescribing home exercises at least once in the last 30 days. RESULTS: The
      compliance strategies used most frequently by Ontario chiropractors were: keeping
      instructions simple (82%, 95% CI = 75-90%); motivating patients by explaining
      exercises in a positive and enthusiastic manner (81%, 95% CI = 74-89%); giving
      patients encouragement, support and praise (80%, 95% CI = 72-88%); prescribing
      exercises that require low-cost equipment (70%, 95% CI = 61-78%); and supplying
      patients with material that helps demonstrate the exercises (62%, 95% CI = 53
      71%) and educating patients by discussing the importance of and benefits to
      exercise (62%, 95% CI = 53-71%). CONCLUSION: There appeared to be respondent
      consensus on the main compliance strategies used by Ontario chiropractors. Now
      that we have a current listing.

PMID- 17549182
TI  - Moving from anecdote to evidence.

PMID- 17549183
TI  - Systematic reviews from the Cochrane Musculoskeletal Group.

PMID- 17549184
TI  - Subtle clinical signs of a spinal cord ependymoma at the cervicothoracic level in
      an adult: a case report.
AB  - A 33-year-old male presented to a chiropractic clinic complaining of chronic,
      recurrent low back pain. Subtle signs of muscle atrophy were noted in the left
      hand during the history taking. This muscle atrophy was reported as having a
      gradual onset spanning the past six months without any precipitating event.
      Cervical, thoracic and lumbar spinal radiographs were deemed unremarkable. Due to
      the progressive nature of the neurological deficit, the patient was referred for
      a neurological consultation. A magnetic resonance imaging (MRI) study was
      performed and revealed an expansive intramedullary lesion between C6 and T1
      suggesting a differential diagnosis of spinal cord ependymoma or astrocytoma. The
      patient underwent surgical excision of the tumour. Pathological report confirmed
      a diagnosis of ependymoma. In the presence of subtle clinical signs, clinicians
      should keep a high index of suspicion for spinal cord tumours.

PMID- 17549185
TI  - The conservative treatment of Trigger thumb using Graston Techniques and Active
      Release Techniques.
AB  - OBJECTIVE: To detail the progress of a patient with unresolved symptoms of
      Trigger thumb who underwent a treatment plan featuring Active Release Technique
      (ART) and Graston Technique. CLINICAL FEATURES: The most important feature is
      painful snapping or restriction of movement, most notably in actively extending
      or flexing the digit. The cause of this flexor tendinopathy is believed to be
      multi-factorial including anatomical variations of the pulley system and
      biomechanical etiologies such as exposure to shear forces and unaccustomed
      activity. Conventional treatment aims at decreasing inflammation through
      corticosteroid injection or surgically removing imposing tissue. INTERVENTION AND
      OUTCOME: The conservative treatment approach utilized in this case involved
      Active Release Technique (ART) and Graston Technique (GT). An activity specific
      rehabilitation protocol was employed to re-establish thumb extensor strength and
      ice was used to control pain and any residual inflammation. Outcome measures
      included subjective pain ratings with range of motion and motion palpation of the
      first right phalangeal joint. Objective measures were made by assessing range of
      motion. CONCLUSION: A patient with trigger thumb appeared to be relieved of his
      pain and disability after a treatment plan of GT and ART.

PMID- 17549186
TI  - Hip fracture presenting as mechanical low back pain subsequent to a fall: a case
      study.
AB  - This case chronicles the assessment and clinical management of a 54 year old
      female patient who presented with post traumatic lower back, hip and lower
      extremity pain, initially attributed to mechanical low back pain but ultimately
      diagnosed as a hip fracture. This case study illustrates a number of important
      issues germane to chiropractic care. These are; the importance of using different
      assessment procedures, combined with clinical experience, in order to
      differentiate between those patients with clinical conditions that are amenable
      to conservative care from those that are not; the usefulness of a tuning fork
      test as a clinical tool in differentiating between hip fracture and mechanical
      spinal pain syndromes and; the impact of falls and fractures among older Canadian
      patients.

PMID- 17549187
TI  - The use of botulinum neurotoxin type A (Botox) for headaches: a case review.
AB  - Chiropractic care is a common treatment sought by patients with headaches. As
      some patients may not benefit from this care, chiropractors must be aware of
      alternative management options. Botox has more recently become a common treatment
      for headaches. A case of a 45-year-old female with chronic headaches and neck
      pain is presented. After lengthy trials of chiropractic manipulation, trigger
      point therapy, and acupuncture, the patient was treated with Botox-A. She
      experienced pain relief following the initial treatment that lasted up to 3-4
      months and has since undergone subsequent trials of Botox with the same results.
      No side effects were experienced. As more health care practitioners are
      recommending Botox, the need for a better understanding of the evidence and
      criteria for referral for Botox treatment is required. As such, chiropractors
      should consider this alternative approach to managing headaches when chiropractic
      management is unsuccessful.

PMID- 17549188
TI  - Oswald Hall, PhD: pioneer Canadian sociologist; 1924-1976.
AB  - At ninety-eight (2006), Oswald Hall is Canada's senior, distinguished
      sociologist. For several decades Dr. Hall's colleagues have acknowledged his
      abiding "contributions to the growth of sociology in Canada and his loyalty to
      the profession."1 The prime purpose of this paper is to document Dr. Hall's
      legacy. It begins by briefly looking at Dr. Hall's origins and early training.
      Then it investigates his graduate and postgraduate education and delves into his
      varied roles as a teacher, researcher, civil servant, and administrator, as well
      as his appointments to various advisory bodies, enquiries, boards and
      associations and concludes with a commentary on Oswald Hall's accomplishments.
      Throughout the paper, Dr. Hall's major publications are reviewed chronologically.
      This study does not include Hall's twenty-seven year involvement with the
      chiropractic profession (1976 to 1998) because that era has been covered
      extensively in the December 2005 issue of the JCCA.2 Much of the article is based
      on testimony from colleagues and friends, as well as quotes from some of Hall's
      unpublished writings and manuscripts. Unpublished Hall quotes are identified in
      the references by their titles and/or dates.

PMID- 17549190
TI  - JCCA 2006;50 (3):172-181. Oakley P, Harrison DD, Harrison DE, Haas J. A rebuttal
      to chiropractic radiologists' view of the 50 year old, linear-no-threshold
      radiation risk model (commentary).

PMID- 17549192
TI  - Can chiropractic survive its chimerical nature?

PMID- 17549194
TI  - Stimulation of myofascial trigger points causes systematic physiological effects.

PMID- 17549197
TI  - Symptomatic improvement in function and disease activity in a patient with
      ankylosing spondylitis utilizing a course of chiropractic therapy: a prospective
      case study.
AB  - BACKGROUND: There is limited outcome measure support for chiropractic
      manipulative therapy in the management of ankylosing spondylitis. An improvement
      in specific indices for both function and disease activity during chiropractic
      therapy for ankylosing spondylitis has not previously been reported. OBJECTIVE:
      To measure changes in function and disease activity in a patient with ankylosing
      spondylitis during a course of chiropractic therapy. The clinical management of
      ankylosing spondylitis, including chiropractic manipulative therapy and the
      implications of this case study are discussed. CLINICAL FEATURES: A 34-year-old
      male with a 10 year diagnosis of ankylosing spondylitis sought chiropractic
      treatment for spinal pain and stiffness. His advanced radiographic signs included
      an increased atlantodental interspace and cervical vertebral ankylosis.
      INTERVENTION AND OUTCOME: The Bath Ankylosing Spondylitis Functional Index
      (BASFI), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), finger-tip
      to-floor distance and chest expansion were assessed during an 18 week course of
      chiropractic spinal manipulation and mobilization therapy. There was a 90%
      improvement in the disease activity index and an 85% improvement in the
      functional index from the pre-treatment baseline, as measured by the BASDAI and
      BASFI respectively. Spinal flexibility and chest expansion also improved.
      CONCLUSION: To the authors knowledge this is the first study to incorporate
      ankylosing spondylitis specific indices, for both disease activity and function,
      to objectively support the use of chiropractic manipulative therapy in the
      management of ankylosing spondylitis. More intensive research is suggested.

PMID- 17549198
TI  - Chiropractic management of musculoskeletal pain secondary to tardive dyskinesia.
AB  - Tardive dyskinesia (TD) is an umbrella term typically used to describe a movement
      disorder associated with the use of neuroleptic (anti-psychotic) medication. It
      is characterized by abnormal, repetitive and involuntary movements. The movements
      may be around the mouth and face (orofacial dyskinesia) and less frequently, in
      the trunk and limbs (trunk and limb dyskinesia). TD occurs in over 20% of those
      using neuroleptic medication continually for longer than three months. A case
      report is presented of a patient affected by TD who suffered mechanical
      musculoskeletal pain secondary to its effects, and was managed by chiropractic
      care.

PMID- 17549200
TI  - Campuses of the LACC.
AB  - In its 94 years the Los Angeles College of Chiropractic (LACC) has occupied at
      least nine main campuses, exclusive of "satellite" facilities and the campuses of
      the dozen or more schools which have amalgamated with the LACC over the years.
      The longest serving of these properties have been in Glendale (1950-1981),
      Whittier (1981-present), and on Venice Boulevard in Los Angeles (1924-1950). This
      paper reviews these several locations and the efforts involved in acquiring and
      refurbishing them for College purposes. Additionally, we note two prospective
      campuses that never quite materialized: in Burbank, 1930 and in Los Gatos, 1975
      76.

PMID- 17549199
TI  - Biomechanical effects of a lumbar support in a mattress.
AB  - For many patients with chronic low back pain, the lack of sleep and sufficient
      rest period that allows some relaxation is a major obstacle to a good quality of
      life. During sleep periods, neuromuscular activity is at a minimal level. The
      major factor influencing the forces on the body, and particularly the spine, is
      gravity. The force of gravity is sufficient to deform soft tissues when the body
      is resting on a mattress. Thus, the goal of this study is to measure the contact
      pressure forces acting on the spine with and without an inflatable support in
      various experimental conditions. Our hypothesis is that a lumbar support will
      distribute the force of gravity more uniformly over the pelvic, lumbar and
      thoracic areas, maintaining the lumbar lordosis, in a supine posture. In this
      study, 10 participants were tested when lying supine in six separate experimental
      conditions. These conditions varied according to the surface (no mattress, foam,
      mattress) and the fact that the support was inflated or not. The dependent
      variable measured was the contact pressure. It was measured using a pressure
      sensor mat (Tekscan). When the cushion was inflated the distribution of contact
      pressure in the different areas (pelvic, lumbar and thoracic) was modified. The
      comparison of the mean forces revealed that when the cushion was not inflated,
      the pressure distribution was mainly localized in the pelvic area. After the
      cushion was inflated, a significant decrease of contact pressure in the pelvic
      region and a significant increase in the lumbar area were observed. Our results
      confirm the hypothesis that a lumbar support inserted in a mattress allows a more
      homogenous distribution of contact pressure over the pelvic, lumbar and thoracic
      areas during supine posture. The use of an inflatable cushion favouring a
      transition of the contact pressure from the pelvic to the lumbar region could
      potentially limit unfavourable compressive and shearing forces acting on the
      lumbar spine.

PMID- 17549201
TI  - The future is ours to create.

PMID- 17549202
TI  - Chiropractic: a specialty with limitations?

PMID- 17549203
TI  - Divided we stand.

PMID- 17549204
TI  - Profile-Simon Dagenais, DC, PhD.

PMID- 17549205
TI  - Profile-Shari Wynd, MASc, DC.

PMID- 17549207
TI  - Clinical decision analysis: an alternate, rigorous approach to making clinical
      decisions and developing treatment recommendations.

PMID- 17549208
TI  - On "phantom risks" associated with diagnostic ionizing radiation: evidence in
      support of revising radiography standards and regulations in chiropractic.

PMID- 17549210
TI  - Management of a low back pain patient with a prosthesis and a foot drop orthotic.
AB  - INTRODUCTION: The effect of altered gait on body mechanics presents a stress on
      patient's sacroiliac joints (SIJ). The gait of the patient is this case report is
      altered because of a transtibial amputation with prosthesis; he also has a foot
      drop orthotic. CLINICAL FEATURES: A 40-year-old man had left sacroiliac pain. The
      pain began 3 days before visiting the clinic and has been constant since its
      onset. It is alleviated by resting on his side. He reported that he had been
      painting his mother's house for 3 days before the pain started. Past history is
      significant for a spinal cord injury with resultant right leg foot drop; in
      addition, he has a left leg prosthesis. INTERVENTION AND OUTCOME: Adjustments to
      the sacroiliac joint were performed on a Zenith-Thompson Terminal Point adjusting
      table, utilizing only motion palpation to assess for subluxation. The adjustments
      consisted of contacting the left posterior superior iliac spine (PSIS) and
      applying 3 successive high-velocity, low-amplitude thrusts to it. Initial visit
      schedules were bi-weekly and progresses to bi-monthly as needed. CONCLUSION:
      Patient with prosthesis can benefit greatly from chiropractic care, to assist
      them in maintaining proper joint motion and gait patterns that allow them to walk
      more freely.

PMID- 17549211
TI  - Oswald Hall, PhD: Chiropractic advocate; 1971 to 1998.
AB  - Oswald Hall is one of the "outsiders" who has profoundly impacted Canadian
      chiropractic and by extension, its various constituencies. The purpose of this
      paper is to document how Dr. Hall used the depth and breadth of knowledge and
      experience assimilated in his career, to interact with the chiropractic
      profession and the Canadian Memorial Chiropractic College (CMCC). Dr. Hall's main
      achievement for chiropractic was to quietly, firmly, yet politely, open doors for
      the acceptance by and of chiropractic and CMCC into the arena of graduate level
      professional education. He did this in three ways: Dr. Hall's first step took
      place in 1973, when as Chair of the Task Force on Chiropractic for the OCH, he
      assisted the committee to make positive recommendations regarding our education
      and practice. Dr. Hall's second step was his contribution to the sociological
      study culminating in the book, "Chiropractors: Do They Help." His third, and most
      complex initiative began in 1982 when he joined the CMCC Board. His stamina and
      affability were tested during his sixteen year tenure on the University
      Affiliation Committee as the College endured protracted, failed attempts to unite
      with the University of Victoria, BC (1988-1992) and York University, Toronto, ON
      (1995-2001).

PMID- 17549209
TI  - Evidence-based protocol for structural rehabilitation of the spine and posture:
      review of clinical biomechanics of posture (CBP) publications.
AB  - BACKGROUND: Although practice protocols exist for SMT and functional
      rehabilitation, no practice protocols exist for structural rehabilitation.
      Traditional chiropractic practice guidelines have been limited to acute and
      chronic pain treatment, with limited inclusion of functional and exclusion of
      structural rehabilitation procedures. OBJECTIVE: (1) To derive an evidence-based
      practice protocol for structural rehabilitation from publications on Clinical
      Biomechanics of Posture (CBP((R))) methods, and (2) to compare the evidence for
      Diversified, SMT, and CBP((R)). METHODS: Clinical control trials utilizing CBP(R)
      methods and spinal manipulative therapy (SMT) were obtained from searches in
      Mantis, CINAHL, and Index Medicus. Using data from SMT review articles, evidence
      for Diversified Technique (as taught in chiropractic colleges), SMT, and CBP((R))
      were rated and compared. RESULTS: From the evidence from Clinical Control Trials
      on SMT and CBP((R)), there is very little evidence support for Diversified (our
      rating = 18), as taught in chiropractic colleges, for the treatment of pain
      subjects, while CBP((R)) (our rating = 46) and SMT for neck pain (rating = 58)
      and low back pain (our rating = 202) have evidence-based support. CONCLUSIONS:
      While CBP((R)) Technique has approximately as much evidence-based support as SMT
      for neck pain, CBP((R)) has more evidence to support its methods than the
      Diversified technique taught in chiropractic colleges, but not as much as SMT for
      low back pain. The evolution of chiropractic specialization has occurred, and
      doctors providing structural-based chiropractic care require protocol guidelines
      for patient quality assurance and standardization. A structural rehabilitation
      protocol was developed based on evidence from CBP((R)) publications.

PMID- 17549212
TI  - Dr. Tom Lawrence: a life in chiropractic.
AB  - He dwelt within the chiropractic orbit from the cradle to the grave. Second
      generation chiropractor Tom Lawrence was a successful professional and family man
      who followed in his father's footsteps and fought the good fight to improve
      chiropractic within his state and nation. His passing closes a chapter of living
      memory of the middle years of the first chiropractic century.

PMID- 17549213
TI  - The Cochrane Library 2005, issue 4: (dates indicate the original date of
      publication, or most recent update).

PMID- 17549214
TI  - Acute onset-low back pain and hip pain secondary to metastatic prostate cancer: a
      case report.
AB  - Prostatic cancer is the second most common cancer among North American men and
      the second leading cause of cancer deaths. It may be incidental or contribute to
      the cause of mechanical back pain. With such high mortality associated with
      metastasis, early detection is essential for appropriate medical management.
      Chiropractors are often consulted for back pain of mechanical origin and are in a
      position to detect conditions in which serious organic pathology may contribute
      to, or mimic benign musculoskeletal back pain. Patient history and clinical
      examination coupled with imaging may greatly increase the index of suspicion of
      prostatic involvement. Outlined is a case where imaging and examination confirmed
      a diagnosis of organic disease in an individual who opted for chiropractic care
      for his back pain, but for whom immediate medical management was essential.

PMID- 17549215
TI  - The cost-effectiveness of a back education program for firefighters: a case
      study.
AB  - SUMMARY OF BACKGROUND DATA: Low Back Pain (LBP) is one of the most common causes
      of disability in the working population, and its impact on industry is enormous.
      The high financial costs of LBP and its apparent relationship with working
      conditions have led to efforts to prevent this condition. Several reviews have
      suggested that there is considerable potential for multimodal preventive
      interventions to cost-effectively reduce the overall burden of illness.
      OBJECTIVES: The objectives of this study were to assess the feasibility of
      implementing a multi-faceted back injury prevention program in the community, and
      to assess the effectiveness of this program. STUDY DESIGN: A case study involving
      92 firefighters from a suburb north of Toronto, Ontario, Canada. METHODS: A back
      education program, called the Back Informed Program, was conducted on-site by a
      trained chiropractor. It offered employees job-specific education, ergonomic
      advice, exercises and pain management, as well as hands-on practice sessions.
      Data on absenteeism due to back injury, and cost of lost work days due to back
      injury were collected between January 1995 and December 1996. Data were compared
      to a municipality that received no such program during the same time period.
      Secondary outcomes, including information attained among the workers were
      qualitatively assessed. Absenteeism and financial data were used to demonstrate
      the potential efficacy of such a program. RESULTS: The results showed a
      significant decrease in the number of days lost due to back injuries in the year
      following implementation of the program. Upon implementation of the Back Informed
      program, there was a reduction of 72.4% in days lost reported over the two year
      period of program implementation. The rate of days lost per worker was 0.64 prior
      to program implementation and dropped to 0.13 two years later. This resulted in
      substantial cost-savings in both direct and indirect costs to the municipality.
      CONCLUSIONS: This study suggests that a multi-faceted, occupation-specific back
      education program may help reduce back injuries and reduce injury-related costs.

PMID- 17549216
TI  - Assessing effects of a semi-customized experimental cervical pillow on
      symptomatic adults with chronic neck pain with and without headache.
AB  - OBJECTIVE: To determine the effects of a semi-customized experimental cervical
      pillow on symptomatic adults with chronic neck pain (with and without headache)
      during a four week study. DESIGN: A randomized controlled trial. SAMPLE SIZE:
      Thirty-six adults were recruited for the trial, and randomly assigned to
      experimental or non-experimental groups of 17 and 19 participants respectively.
      SUBJECTS: Adults with chronic biomechanical neck pain who were recruited from the
      Canadian Memorial Chiropractic College (CMCC) Walk-in Clinic. OUTCOME MEASURES:
      Subjective findings were assessed using a mail-in self-report daily pain diary,
      and the CMCC Neck Disability Index (NDI). STATISTICAL ANALYSIS: Using repeated
      measure analysis of variance weekly NDI scores, average weekly AM and PM pain
      scores between the experimental and non-experimental groups were compared
      throughout the study. RESULTS: The experimental group had statistically
      significant lower NDI scores (p < 0.05) than the non-experimental group. The
      average weekly AM scores were lower and statistically significant (p < 0.05) in
      the experimental group. The PM scores in the experimental group were lower but
      not statistically significant than the other group. CONCLUSIONS: The study
      results show that compared to conventional pillows, this experimental semi
      customized cervical pillow was effective in reducing low-level neck pain
      intensity, especially in the morning following its use in a 4 week long study.

PMID- 17549217
TI  - The effect of low force chiropractic adjustments on body surface electromagnetic
      field.
AB  - OBJECTIVE: The purpose of this study was to investigate the body surface
      electromagnetic field (EMF) changes using a sensitive magnetometer before and
      after a specific Toftness chiropractic adjustment in asymptomatic human subjects.
      METHOD: Forty-four subjects were randomly assigned into control (20 subjects) and
      experimental groups (24 subjects) in a pre and post-test design. The Triaxial
      Fluxgate Magnetometer FGM-5DTAA (Walker Scientific, Worcester, Massachusetts)
      with five digit display and resolution of 1 nanotesla (nT) was used for EMF
      detection. The EMF in the research room and on the adjustment table was monitored
      and recorded. The subjects' body surface (cervical, thoracic, lumbar and sacral
      areas) EMF was determined in the prone position before and after the chiropractic
      adjustment. A low force Toftness chiropractic adjustment was applied to the
      cervical, thoracic, lumbar and sacral areas as determined by the practitioner.
      RESULTS: The EMF in the research room was recorded as 41611 nT at the Z axis
      (earth field), 13761 nT at the X axis and 7438 nT at the Y axis. The EMF on the
      adjusting table changed minimally during the 15 minute observation period. The
      EMF on the subjects' body surface decreased at 4 spinal locations after
      chiropractic adjustment. The EMF (mean +/- SD in nT) decreased significantly at
      the cervical region from 42449 +/- 907 to 41643 +/- 1165 (p < 0.01) and at the
      sacral regions from 43206 +/- 760 to 42713 +/- 552 (p < 0.01). The EMF at the
      lumbar and thoracic regions decreased but did not reach a statistically
      significant level. No significant changes of the body surface EMF were found in
      the control group. CONCLUSION: A low force Toftness chiropractic adjustment in
      the cervical and sacral areas resulted in a significant reduction of the cervical
      and sacral surface EMF. No significant body surface EMF changes were observed in
      the lumbar and thoracic regions. The mechanisms of the EMF reduction after
      chiropractic adjustment are not known.

PMID- 17549218
TI  - Ian Douglass Coulter, PhD: CMCC'S adventurous president.
AB  - This paper focuses on Dr. Ian Coulter's accomplishments from the time he became
      Executive Vice-President of CMCC in 1981, until he ended his presidency with a
      year's administrative leave in 1990. Annual planning initiatives, pedagogy,
      scholarship, conflicts, and the quest for university affiliation are discussed as
      well as his legacy to the College and the chiropractic profession. The term
      "adventurous" was first attributed to Coulter by Oswald Hall, PhD, Professor
      Emeritus, University of Toronto who had worked closely with Coulter in a major
      investigation of the chiropractic profession from 1976 to 1979. Throughout this
      article the author tries to capture the spirit of daring, innovation and
      intellect that permeated Coulter's presidency, enthralling his advocates and
      confounding his detractors.

PMID- 17549219
TI  - The Canadian Chiropractic Association and the Canadian Federation of Chiropractic
      Regulatory Boards Clinical Practice Guidelines Development Initiative (The
      CCA/CFCRB-CPG) development, dissemination, implementation, evaluation, and
      revision (DevDIER) plan.

PMID- 17549220
TI  - A review of the literature pertaining to the efficacy, safety, educational
      requirements, uses and usage of mechanical adjusting devices: Part 1 of 2.
AB  - Over the past decade, mechanical adjusting devices (MADs) were a major source of
      debate within the Chiropractors' Association of Saskatchewan (CAS). Since
      Saskatchewan was the only jurisdiction in North America to prohibit the use of
      MADs, the CAS established a committee in 2001 to review the literature on MADs.
      The committee evaluated the literature on the efficacy, safety, and uses of
      moving stylus instruments within chiropractic practice, and the educational
      requirements for chiropractic practice. Following the rating criteria for the
      evaluation of evidence, as outlined in the Clinical Guidelines for Chiropractic
      Practice in Canada (1994), the committee reviewed 55 articles - all of which
      pertained to the Activator. Of the 55 articles, 13 were eliminated from the final
      study. Of the 42 remaining articles, 6 were rated as class 1 evidence; 11 were
      rated as class 2 evidence and 25 were rated as class 3 evidence. In this article 
      the first in a series of two - the background and the methods utilized by the
      MAD committee's activities are described, as well as the results for the review
      of the literature on efficacy. Of the 21 articles related to efficacy, five were
      identified as Class 1 evidence; 4 were identified as Class 2 evidence; and 12
      were identified as Class 3. Overall, the committee reached consensus that the MAD
      procedures using the Activator were as effective as manual (HVLA) procedures in
      producing clinical benefit and biological change. A minority report was also
      written, arguing that there was not enough evidence to support or refute the
      efficacy of MADs.

PMID- 17549222
TI  - Canadian chiropractic researchers: Shari Wynd.

PMID- 17549221
TI  - Orthopaedics and chiropractic, a close relationship.

PMID- 17549223
TI  - Fibromyalgia: revisiting the literature.
AB  - Fibromyalgia has a distinct clinical presentation. With no distinct
      characteristic beyond the presence of 11 or more tender points and chronic pain
      in all four quadrants of the body, it represents one extreme of a normal
      distribution of pain states. Research exploration utilizing the ACR criteria has
      not found solid empirical evidence to link the finding of multiple tender points
      to a specific pathological process. These points may be present as a concomitant
      finding with psychological disease states but they have not lead to further
      etiological understanding. Measurement of outcomes is difficult and the prognosis
      for patients in the specialty care setting is poor, however in the general
      population the prognosis is variable, and includes improvement without treatment.
      The success of treatments has been limited mainly to helping patients improve
      their ability to cope with, but not to eliminate the tender points.

PMID- 17549224
TI  - Discitis in an adult following acupuncture treatment: a case report.
AB  - Recent papers, including a review conducted by van Tulder et al., have suggested
      that there is paucity of information as to the efficacy of acupuncture treatment.
      However, there has been a significant increase in the use of acupuncture therapy
      for treatment of various ailments, including lower back pain. Chiropractors,
      along with other health care professionals, are using acupuncture as an adjunct
      to their main therapeutic intervention as demonstrated by a recent survey by the
      Canadian Chiropractic Protective Association (CCPA). However, like many other
      interventions, including NSAIDs and spinal manipulations, signs of side effects
      should be monitored when acupuncture treatments are considered. Recent papers
      have noted such complications as pneumothorax and hepatitis following acupuncture
      treatments. A case is presented in which a patient, who received previous
      acupuncture treatments, presented to a chiropractic clinic complaining of low
      back and leg pain. Early recognition of potential complications after acupuncture
      treatment may minimize significant impairments and disability.

PMID- 17549225
TI  - Avascular necrosis of the hip in a 41-year-old male: a case study.
AB  - This case deals with the avascular necrosis or osteonecrosis of the femoral head
      in a 41-year-old male presenting to a chiropractor's office. In addition to the
      clinical picture, diagnostic imaging should be performed to confirm the presence
      and extent of hip avascular necrosis. Referral to an orthopedic specialist is key
      and treatment is mainly surgical.

PMID- 17549226
TI  - Rehabilitation of a patient with a rare multi-level isthmic spondylolisthesis: a
      case report.
AB  - A rare multi-level isthmic spondylolisthesis was discovered in a young male
      patient following an acute onset of low back pain. The prevalence of
      spondylolisthesis in the adult population is low and it is believed that the
      prevalence of multiple level spondylolisthesis is even rarer. A combination of
      onset of ambulation, hereditary factors, and sports involving hyper-extension of
      the spine are predisposing factors. Conservative treatment such as chiropractic
      manipulation and rehabilitation of the spine are first treatment options before
      surgical intervention is considered. The clinical presentations, radiographic
      features, treatment options including rehabilitation methods are discussed.

PMID- 17549227
TI  - A review of the literature pertaining to the efficacy, safety, educational
      requirements, uses and usage of mechanical adjusting devices: Part 2 of 2.
AB  - Over the past decade, mechanical adjusting devices (MADs) were a major source of
      debate within the Chiropractors' Association of Saskatchewan (CAS). Since
      Saskatchewan was the only jurisdiction in North America to prohibit the use of
      MADs, the CAS established a committee in 2001 to review the literature on MADs.
      The committee evaluated the literature on the efficacy, safety, and uses of
      moving stylus instruments within chiropractic practice, and the educational
      requirements for chiropractic practice. Following the rating criteria for the
      evaluation of evidence, as outlined in the Clinical Guidelines for Chiropractic
      Practice in Canada (1994), the committee reviewed 55 articles - all of which
      pertained to the Activator. Of the 55 articles, 13 were eliminated from the final
      study. Of the 42 remaining articles, 6 were rated as class 1 evidence; 11 were
      rated as class 2 evidence and 25 were rated as class 3 evidence. In this article 
      the second in a series of two - we review the results of uses and usage, safety
      and educational requirements. Of the 30 articles designated under the category of
      usage, 3 were rated as Class 1 evidence; 9 studies were classified as Class 2
      evidence and 18 were rated as Class 3 evidence. Overall the committee reached
      consensus that in clinical practice, there is broad application of these
      procedures. A minority report was written arguing that the reviewer was unable to
      reach a conclusion about the use of the Activator Instrument other than it is
      used as a clinical and research tool. Of the 16 studies that dealt either
      explicitly or implicitly with safety, 4 were Class 1 evidence; 3 were Class 2
      evidence and 9 were Class 3 evidence. Overall the committee reached consensus
      that the evidence supports that the Activator instrument is safe and has no more
      relative risk than do manual HVLA procedures. A minority report was written
      arguing that there is no evidence either to support or refute the view that MAD
      is safe. Of the 5 studies that dealt with educational requirements, all were
      Class 3 evidence. Overall the committee reached consensus that there was no
      evidence in the literature with respect to educational requirements to form any
      conclusions. A minority report was written offering opinion that there is
      evidence with respect to educational requirements.

PMID- 17549229
TI  - Is there room for paradox in CAM?

PMID- 17549228
TI  - A cluster-randomised trial evaluating an intervention for patients with stress
      related mental disorders and sick leave in primary care.
AB  - OBJECTIVE: Mental health problems often affect functioning to such an extent that
      they result in sick leave. The worldwide reported prevalence of mental health
      problems in the working population is 10%-18%. In developed countries, mental
      health problems are one of the main grounds for receiving disability benefits. In
      up to 90% of cases the cause is stress-related, and health-care utilisation is
      mainly restricted to primary care. The aim of this study was to assess the
      effectiveness of our Minimal Intervention for Stress-related mental disorders
      with Sick leave (MISS) in primary care, which is intended to reduce sick leave
      and prevent chronicity of symptoms. DESIGN: Cluster-randomised controlled
      educational trial. SETTING: Primary health-care practices in the Amsterdam area,
      The Netherlands. PARTICIPANTS: A total of 433 patients (MISS n = 227, usual care
      [UC] n = 206) with sick leave and self-reported elevated level of distress.
      INTERVENTIONS: Forty-six primary care physicians were randomised to either
      receive training in the MISS or to provide UC. Eligible patients were screened by
      mail. OUTCOME MEASURES: The primary outcome measure was duration of sick leave
      until lasting full return to work. The secondary outcomes were levels of self
      reported distress, depression, anxiety, and somatisation. RESULTS: No superior
      effect of the MISS was found on duration of sick leave (hazard ratio 1.06, 95%
      confidence interval 0.87-1.29) nor on severity of self-reported symptoms.
      CONCLUSIONS: We found no evidence that the MISS is more effective than UC in our
      study sample of distressed patients. Continuing research should focus on the
      potential beneficial effects of the MISS; we need to investigate which elements
      of the intervention might be useful and which elements should be adjusted to make
      the MISS effective.

PMID- 17549230
TI  - New light on chromotherapy: Grakov's 'Virtual Scanning' system of medical
      assessment and treatment.
AB  - Virtual Scanning incorporates novel uses of colored light into its system of
      health assessment and therapy. Independent investigations of its effectiveness in
      Russia and the UK have revealed unique abilities to correct incipient and fully
      developed chronic conditions. As such it forms an important new addition to the
      field of Chromotherapy. It differs from most others, in that its development
      depended on discoveries in neuroscience by its inventor, and subsequent
      application of new models in computational neuroscience.

PMID- 17549231
TI  - Traditional phytochemistry: identification of drug by 'taste'.
AB  - Ayurveda, the system of traditional medicine from India, holds that 'Rasa', a
      concept roughly corresponding to taste, is a basis for identifying
      pharmacological properties of plants and other materia medica used in Dravyaguna
      its system of phytomedicine. This idea has recently found support in studies of
      ibuprofen, the pharmacological properties of which are similar to those of
      oleocanthal, because the two substances have very similar tastes. This paper
      discusses a possible scientific approach to understanding the Ayurvedic
      (hypo)thesis in terms of the stereochemical basis of both pharamaco-activity and
      taste, and the numbers of possible pharmaco-active compounds that 'Rasa' may be
      able to distinguish. We conclude that molecules binding to a specific enzyme
      active site should have their own 'Rasa', and that the number of different
      subjectively experienced 'tastes' is more than enough to distinguish between
      molecular shapes binding to all enzyme active sites in the body.

PMID- 17549232
TI  - Immunology and homeopathy. 5. The rationale of the 'Simile'.
AB  - The foundation of homeopathic medicine is the 'Similia Principle', also known as
      the 'Principle of Similarity' or also as the 'Simile', which reflects the
      inversion of pharmacological effects in healthy subjects as compared with sick
      ones. This article describes the inversion of effects, a widespread medical
      phenomenon, through three possible mechanisms: non-linearity of dose-response
      relationship, different initial pathophysiological states of the organism, and
      pharmacodynamics of body response to the medicine. Based on the systemic networks
      which play an important role in response to stress, a unitary and general model
      is designed: homeopathic medicines could interact with sensitive (primed)
      regulation systems through complex information, which simulate the disorders of
      natural disease. Reorganization of regulation systems, through a coherent
      response to the medicine, could pave the way to the healing of the cellular,
      tissue and neuro-immuno-endocrine homeodynamics. Preliminary evidence is
      suggesting that even ultra-low doses and high-dilutions of drugs may incorporate
      structural or frequency information and interact with chaotic dynamics and
      physical-electromagnetic levels of regulation. From the clinical standpoint, the
      'simile' can be regarded as a heuristic principle, according to which the
      detailed knowledge of pathogenic effects of drugs, associated with careful
      analysis of signs and symptoms of the ill subject, could assist in identifying
      homeopathic remedies with high grade of specificity for the individual case.

PMID- 17549233
TI  - Effectiveness of massage therapy for chronic, non-malignant pain: a review.
AB  - Previous reviews of massage therapy for chronic, non-malignant pain have focused
      on discrete pain conditions. This article aims to provide a broad overview of the
      literature on the effectiveness of massage for a variety of chronic, non
      malignant pain complaints to identify gaps in the research and to inform future
      clinical trials. Computerized databases were searched for relevant studies
      including prior reviews and primary trials of massage therapy for chronic, non
      malignant pain. Existing research provides fairly robust support for the
      analgesic effects of massage for non-specific low back pain, but only moderate
      support for such effects on shoulder pain and headache pain. There is only
      modest, preliminary support for massage in the treatment of fibromyalgia, mixed
      chronic pain conditions, neck pain and carpal tunnel syndrome. Thus, research to
      date provides varying levels of evidence for the benefits of massage therapy for
      different chronic pain conditions. Future studies should employ rigorous study
      designs and include follow-up assessments for additional quantification of the
      longer-term effects of massage on chronic pain.

PMID- 17549235
TI  - Radiation response of cultured human cells is unaffected by Johrei.
AB  - Johrei has been credited with healing thousands from radiation wounds after the
      Hiroshima and Nagasaki bombs in 1945. This alternative medical therapy is
      becoming increasingly popular in the United States, as are other Energy Medicine
      modalities that purport to influence a universal healing energy. Human brain
      cells were cultured and exposed to increasing doses of ionizing radiation.
      Experienced Johrei practitioners directed healing intentionality toward the cells
      for 30 min from a distance of 20 cm and the fate of the cells was observed by
      computerized time-lapse microscopy. Cell death and cell divisions were tallied
      every 30 min before, during and after Johrei treatment for a total of 22.5 h. An
      equal number of control experiments were conducted in which cells were irradiated
      but did not receive Johrei treatment. Samples were assigned to treatment
      conditions randomly and data analysis was conducted in a blinded fashion.
      Radiation exposure decreased the rate of cell division (cell cycle arrest) in a
      dose-dependent manner. Division rates were estimated for each 30 min and averaged
      over 8 independent experiments (4 control and 4 with Johrei treatment) for each
      of 4 doses of X-rays (0, 2, 4 and 8 Gy). Because few cell deaths were observed,
      pooled data from the entire observation period were used to estimate death rates.
      Analysis of variance did not reveal any significant differences on division rate
      or death rate between treatment groups. Only radiation dose was statistically
      significant. We found no indication that the radiation response of cultured cells
      is affected by Johrei treatment.

PMID- 17549234
TI  - Curcumin in cell death processes: a challenge for CAM of age-related pathologies.
AB  - Curcumin, the yellow pigment from the rhizoma of Curcuma longa, is a widely
      studied phytochemical which has a variety of biological activities: anti
      inflammatory and anti-oxidative. In this review we discuss the biological
      mechanisms and possible clinical effects of curcumin treatment on cancer therapy,
      and neurodegenerative diseases such as Alzheimer's Disease, with particular
      attention to the cell death processes induced by curcumin. Since oxidative stress
      and inflammation are major determinants of the aging process, we also argue that
      curcumin can have a more general effect that slows down the rate of aging.
      Finally, the effects of curcumin can be described as xenohormetic, since it
      activates a sort of stress response in mammalian cells.

PMID- 17549236
TI  - Psychological stress-induced oxidative stress as a model of sub-healthy condition
      and the effect of TCM.
AB  - Distress-mediated tissue oxidative stress was examined as a model of sub-healthy
      condition defined in traditional Chinese medicine theory. Mice were subjected to
      psychologically stressful conditions by whiskers removal. Under this condition,
      spontaneous locomotive activity was significantly enhanced in the dark (P < 0.05
      versus the control mice in three different movements), and
      granulocytes/lymphocytes balance shifted to granulocytes. At the same time,
      peroxynitrite level in blood plasma increased to approximately 180% from that of
      the control mice at 6 h after removal of the whiskers (P < 0.01), and was
      maintained even after 12 h. Both protein carbonyl formation and lipid
      peroxidation were significantly increased under this condition in brain, heart,
      liver and spleen at 6 h after removal of whiskers (P < 0.05 or P < 0.01), and
      these levels were maximized after 12 h (increased to 120-160%, P < 0.05 or P <
      0.01). The oxidative tissue injuries observed at 12 h after the removal of the
      whiskers were effectively prevented by two traditional Chinese medicine formula:
      Shengmai San (SMS) and Ling Gui Zhu Gan Tang (LGZGT), when administered for 5
      days before the removal of the whiskers. Therefore, this stress model is
      considered useful in assessing the preventive potential of antioxidants and
      antioxidant-based herbal mixtures in treating the pathophysiology associated with
      psychological or emotional distress.

PMID- 17549237
TI  - Nourishing Yin and promoting blood circulation of TCM to treat hemorheologic
      disorder induced by diabetes mellitus in rats.
AB  - Diabetes mellitus, DM, is commonly accompanied with various stages of
      hemorheologic disturbances that are the main causes of the development of chronic
      DM. In this study, simple Chinese material medica [yang-yin jiang-tang
      preparation (YYJT)] was given to alloxan-induced DM rats and analyzed to compare
      the changes of fasting blood glucose (FBG), fasting insulin (FINS), hemorheologic
      parameters and insulin-like growth factor II (IGF-II) before and after
      administration. The results suggested that YYJT can significantly downregulate
      FBG (P < 0.005), improve insulin resistance and beta-cell secretion (P < 0.05),
      decrease whole blood viscosity at low and high shear rates, gathering of blood
      index test (GIT) and fibrinogen (FIB) (P < 0.05), and enlarge the function of IGF
      II (P < 0.05). We concluded that YYJT could prevent and treat hemorheologic
      disorder in DM rats by means of reducing glucose, improving insulin resistance
      and elevating IGF-II.

PMID- 17549238
TI  - Inhibition of release of vasoactive and inflammatory mediators in airway and
      vascular tissues and macrophages by a chinese herbal medicine formula for
      allergic rhinitis.
AB  - Herbal therapies are being used increasingly for the treatment of allergic
      rhinitis. The aim of this study was to investigate the possible pharmacological
      actions and cellular targets of a Chinese herbal formula (RCM-101), which was
      previously shown to be effective in reducing seasonal allergic rhinitis symptoms
      in a randomized, placebo-controlled clinical trial. Rat and guinea pig isolated
      tissues (trachea and aorta) were used to study the effects of RCM-101 on
      responses to various mediators. Production of leukotriene B(4) in porcine
      neutrophils and of prostaglandin E(2) and nitric oxide (NO) in Raw 264.7 cells
      were also measured. In rat and guinea pig tracheal preparations, RCM-101
      inhibited contractile responses to compound 48/80 but not those to histamine
      (guinea pig preparations) or serotonin (rat preparations). Contractile responses
      of guinea pig tracheal preparations to carbachol and leukotriene C(4,) and
      relaxant responses to substance P and prostaglandin E(2) were not affected by RCM
      101. In rat aortic preparations, precontracted with phenylephrine, endothelium
      dependent relaxant responses to acetylcholine and endothelium-independent
      relaxant responses to sodium nitroprusside were not affected by RCM-101. However,
      RCM-101 inhibited relaxations to l-arginine in endothelium-denuded rat aortic
      preparations, which had been pre-incubated with lipopolysaccharide. RCM-101 did
      not affect leukotriene B(4) formation in isolated porcine neutrophils, induced by
      the calcium ionophore A23187; however, it inhibited prostaglandin E(2) and NO
      production in lipopolysaccharide-stimulated murine macrophages (Raw 264.7
      cells).The findings indicate that RCM-101 may have multiple inhibitory actions on
      the release and/or synthesis of inflammatory mediators involved in allergic
      rhinitis.

PMID- 17549239
TI  - Collagen Synthesis in tenocytes, ligament cells and chondrocytes exposed to a
      combination of Glucosamine HCl and chondroitin sulfate.
AB  - Clinical testing of the nutraceuticals glucosamine (glcN) and chondroitin sulfate
      (CS) has shown efficacy in providing relief from symptoms in osteoarthritic
      patients. In vitro and in vivo studies support existence of a synergistic
      relationship upregulating synthetic activity in chondrocytes. A combination of
      glcN and CS may also be useful as adjunct therapy in sports-related injuries if
      similar upregulation of collagen synthesis is elicited in accessory ligament and
      tendon joint tissue. Collagen and non-collagenous protein (NCP) synthesis in
      cultures of bovine tenocytes, ligament cells and chondrocytes exposed to glcN +
      CS were assayed by uptake of radiolabeled proline into collagenase-sensitive
      material. Assay of radiolabel in hydroxyproline (a specific marker for collagen
      synthesis) following HPLC isolation confirmed the specificity of the metabolic
      effect. Synthesis of total collagenase-sensitive material was maximally
      upregulated at physiologically obtainable doses of glcN + CS. Tissue response
      followed the sequence ligament cells (+69%) > chondrocytes (+56%) > tenocytes
      (+22%). Labeled hydroxyproline increased by 132% in ligament cells, 27% in
      tenocytes and 49% in epitendon cells after a 48 h exposure to 5 mug ml(-1) glcN +
      4 mug ml(-1) CS. Low dose combinations of glcN and CS effectively stimulate in
      vitro collagen and NCP synthesis by ligament cells, tenocytes and chondrocytes.
      Hence, therapeutic use following accessory joint tissue trauma may help augment
      repair processes.

PMID- 17549240
TI  - Ki-energy (life-energy) stimulates osteoblastic cells and inhibits the formation
      of osteoclast-like cells in bone cell culture models.
AB  - Some practitioners of the Nishino Breathing Method (NBM) were found to have a
      higher bone density than the average values of age- and gender-matched non
      practitioners. Using bone cell culture models, we investigated a possible
      mechanism behind this observation. For the study of bone mineralization, we
      performed the following two experiments using cultured osteoblastic MC3T3-E1
      cells: (i) Kozo Nishino, a Japanese Ki expert, sent Ki-energy to the cells once
      for 5 or 10 min after they were seeded in culture dishes in the presence of 10%
      fetal bovine serum (FBS). They were incubated for 72 h and the cells were
      counted. The number in the dish with 10-min Ki-exposure was significantly greater
      than that in the control (P < 0.01 with n = 8). We performed a reverse
      transcription-polymerase chain reaction (RT-PCR) study using these cells, but the
      mRNA expressions did not change significantly. (ii) After cells were incubated
      for 72 h without Ki-exposure (in the presence of FBS), they were further cultured
      for 48 h (in the absence of FBS) to promote differentiation. At the beginning of
      the second culture stage, Ki was applied once for 10 min. After 48 h, RT-PCR was
      performed. The mRNA expressions which are related to bone mineralization, such as
      Runx2, alpha1(I) collagen, alkaline phosphatase and osteocalcin, increased
      significantly (P < 0.05 and n = 4 for all). For the bone resorption study, we
      used mouse marrow cultures, which can form osteoclast-like cells in the presence
      of (1-34) parathyroid hormone (PTH), and stimulate resorption. We exposed these
      cells to Ki-energy twice for the duration of 5 or 10 min on day 0 and day 4. On
      day 7, the cells were counted. The number of osteoclast-like cells in dishes with
      Ki exposure was significantly smaller than those in control dishes (P < 0.05 with
      n = 5). The difference between 5-min exposure and 10-min exposure was not
      statistically significant. All of our data suggest that the Ki-effect on
      osteoporosis should be further explored.

PMID- 17549241
TI  - Potential synergism between hypnosis and acupuncture-is the whole more than the
      sum of its parts?
AB  - Both hypnosis and acupuncture have gained credibility over the years in their
      effectiveness for treating various health conditions. Currently, each of these
      treatments is administered in distinct settings and separate times. That is, even
      if patients receive both treatments as part of a multidimensional therapeutic
      program, they would typically receive them separately rather than simultaneously
      at the same session. This separation however might be undesirable since, at least
      theoretically, hypnosis and acupuncture could potentially augment each other if
      administered concomitantly. In this article we outline the rationale for this
      hypothesis and discuss the potential ramifications of its implementation.

PMID- 17549242
TI  - Efficacy of Sanfujiu to treat allergies: patient outcomes at 1 year after
      treatment.
AB  - Sanfujiu is a treatment method of applying herbal paste onto the acupoints
      Fengmen and Feishu during the three hottest days of summer to treat patients with
      allergies. The objectives of this study were to determine the treatment efficacy
      at 1 year after the Sanfujiu treatment, and examine variations in the perceived
      efficacy of Sanfujiu among different subgroups, based on the patients' ages,
      diagnoses and number of reactive symptoms immediately after the treatment. We
      enrolled 105 patients who completed Sanfujiu treatment at a medical university
      hospital in Taipei as the subjects. One year after treatment, trained
      interviewers conducted telephone interviews with the patients. Approximately 60%
      of them perceived the treatment as being effective at 1 year later, which was
      higher than that at 1 week after treatment (45.7%). Younger subjects (<19 years
      of age) and patients with asthma were more likely to report the treatment as
      being effective. Patients who had more reactive symptoms after the third Sanfujiu
      treatment were more likely to report the treatment as being effective. The
      results demonstrated that Sanfujiu was moderately effective, as perceived by
      patients in Taiwan, in treating their allergic symptoms.

PMID- 17549243
TI  - Three case reports to illustrate clinical applications in the use of erythrocyte
      transketolase.
AB  - Non-caloric nutrients (NCN) are extremely numerous and it is more than obvious
      that they work in a team relationship. These vitally important interactions are,
      for the most part, poorly understood. These brief case reports illustrate this in
      the therapeutic use of thiamin in a clinical setting. The initially abnormal
      erythrocyte transketolase activity (TKA) and/or the thiamin pyrophosphate effect
      (TPPE), indicating intracellular cofactor deficiency, usually improves with
      thiamin administration. Biochemical correction of the abnormality is, however,
      invariably dependent on the provision of other NCN, especially magnesium. In two
      patients reported here, this correction required several infusions containing
      magnesium and other NCN administered intravenously. In a third patient,
      hemoconcentration associated with an abnormal TPPE was normalized after
      administration of nutrients that included thiamin and magnesium.

PMID- 17549244
TI  - Are users of complementary and alternative medicine sicker than non-users?
AB  - Higher utilization of complementary and alternative medicine (CAM), both in cross
      sections and over time, is commonly related to better socioeconomic status and to
      increased dissatisfaction with conventional medicine and its values. Little is
      known about health differences between users and non-users of CAM. The objective
      of the paper is to explore the difference in health measured by the SF-36
      instrument between users and non-users of CAM, and to estimate the relative
      importance of the SF-36 health domains scales to the likelihood of consulting CAM
      providers. Interviews were used to collect information from a sample of 2000
      persons in 1993 and 2500 persons in 2000, representing the Israeli Jewish urban
      population aged 45-75 in those years. Bivariate and logistic regression analyses
      were used to explore the above associations. The results show that while users of
      CAM enjoy higher socioeconomic status and younger age, they tend to report worse
      health than non-users on the eight SF-36 health domains scales in both years.
      However, controlling for personal characteristics, lower scores on the bodily
      pain, role-emotional and vitality scales are related to greater likelihood of CAM
      use in 2000. In 1993, no scale had a significant adjusted association with the
      use of CAM. The conclusions are that CAM users tend to report worse health. With
      CAM becoming a mainstream, though somewhat luxurious, medical practice, pain and
      affective-emotional distress are the main drivers of CAM use.

PMID- 17549245
TI  - The Canadian Natural Health Products (NHP) regulations: industry compliance
      motivations.
AB  - This qualitative study explores corporations' motivations to comply with new
      natural health products (NHP) Regulations in Canada. Interviews were conducted
      with representatives from 20 Canadian NHP companies. Findings show that the
      rationale for compliance differs for large compared to small and medium-sized
      enterprises (SMEs). Large firms are motivated to comply with the regulations
      because of the deterrent fear of negative media coverage, social motivations,
      ability to comply and maintaining a competitive market advantage. In contrast,
      SMEs are motivated to comply due to the deterrent fear of legal prosecution and a
      sense of duty.

PMID- 17549246
TI  - Mitochondrial nutrition as a strategy for neuroprotection in Parkinson's disease
      research focus in the department of alternative medicine and experimental
      therapeutics at Hokuriku University.

PMID- 17549247
TI  - At the helm of the NIDDK.

PMID- 17549248
TI  - Gene therapy for severe combined immunodeficiency: are we there yet?
AB  - Inherited and acquired diseases of the hematopoietic system can be cured by
      allogeneic hematopoietic stem cell transplantation. This treatment strategy is
      highly successful when an HLA-matched sibling donor is available, but if not, few
      therapeutic options exist. Gene-modified, autologous bone marrow transplantation
      can circumvent the severe immunological complications that occur when a related
      HLA-mismatched donor is used and thus represents an attractive alternative. In
      this review, we summarize the advantages and limitations associated with the use
      of gene therapy to cure SCID. Insertional mutagenesis and technological
      improvements aimed at increasing the safety of this strategy are also discussed.

PMID- 17549249
TI  - Adoptive T cell therapy for cancer in the clinic.
AB  - The transfusion of lymphocytes, referred to as adoptive T cell therapy, is being
      tested for the treatment of cancer and chronic infections. Adoptive T cell
      therapy has the potential to enhance antitumor immunity, augment vaccine
      efficacy, and limit graft-versus-host disease. This form of personalized medicine
      is now in various early- and late-stage clinical trials. These trials are
      currently testing strategies to infuse tumor-infiltrating lymphocytes, CTLs, Th
      cells, and Tregs. Improved molecular biology techniques have also increased
      enthusiasm and feasibility for testing genetically engineered T cells. The
      current status of the field and prospects for clinical translation are reviewed
      herein.

PMID- 17549250
TI  - Vascular biology and bone formation: hints from HIF.
AB  - In this issue of the JCI, Wang, Clemens, and colleagues demonstrate that hypoxia
      inducible factor alpha (HIF alpha) signaling in bone-building osteoblasts is
      central to the coupling of angiogenesis and long bone development in mice (see
      the related article beginning on page 1616). They show that bone formation
      controlled by osteoblast HIF alpha signaling is not cell autonomous but is
      coupled to skeletal angiogenesis dependent upon VEGF signaling. Thus, strategies
      that promote HIF alpha signaling in osteoblasts may augment bone formation and
      accelerate fracture repair.

PMID- 17549251
TI  - Sizing up sialic acid in glomerular disease.
AB  - A new study by Galeano and colleagues in this issue of the JCI reports the first
      glomerular disease caused by a genetic defect in sialic acid biosynthesis (see
      the related article beginning on page 1585). Mice that harbor mutations in the
      Gne/Mnk gene produce lower amounts of sialic acid, suffer from hematuria,
      proteinuria, and structural defects in the glomerulus and die within days after
      birth. Remarkably, the lesion can be reversed through dietary addition of N
      acetylmannosamine, a sialic acid precursor, raising the intriguing possibility
      that this approach might have therapeutic benefit in patients with glomerular
      disease.

PMID- 17549252
TI  - A beneficial role for IL-1 beta in Alzheimer disease?
AB  - While the term neuroinflammation often conjures up images of cellular damage,
      mounting evidence suggests that certain proinflammatory molecules, such as the
      cytokine IL-1 beta, may have beneficial and protective effects. In a report in
      this issue of the JCI, Shaftel and coworkers have generated an elegant mouse
      model in which local hippocampal overexpression of IL-1 beta in an Alzheimer
      disease (AD) transgenic mouse model resulted not in the expected exacerbation of
      the amyloid beta plaque deposition common to AD, but instead in plaque
      amelioration (see the related article beginning on page 1595). Thus, manipulation
      of the immune system may be a potential therapeutic approach to protect against
      AD, although further studies are needed to understand all of the downstream
      effects of this manipulation.

PMID- 17549253
TI  - Unchecked thrombin is bad news for troubled arteries.
AB  - Thrombin is clearly a key trigger of thrombosis, the proximal cause of most
      morbidity and mortality in atherosclerotic cardiovascular disease. Might thrombin
      also contribute to longer-term, structural changes in the arterial wall that
      promote narrowing and clotting? A study in this issue of the JCI argues that it
      can. Aihara et al. report that haploinsufficiency of heparin cofactor II, a
      glycosaminoglycan-dependent thrombin inhibitor, exacerbates injury- or
      hyperlipidemia-induced arterial lesion formation in mice, possibly by excessive
      thrombin signaling through protease-activated receptors (see the related article
      beginning on page 1514).

PMID- 17549254
TI  - Strain-dependent embryonic lethality and exaggerated vascular remodeling in
      heparin cofactor II-deficient mice.
AB  - Heparin cofactor II (HCII) specifically inhibits thrombin action at sites of
      injured arterial wall, and patients with HCII deficiency exhibit advanced
      atherosclerosis. However, the in vivo effects and the molecular mechanism
      underlying the action of HCII during vascular remodeling remain elusive. To
      clarify the role of HCII in vascular remodeling, we generated HCII-deficient mice
      by gene targeting. In contrast to a previous report, HCII(-/-) mice were
      embryonically lethal. In HCII(+/-) mice, prominent intimal hyperplasia with
      increased cellular proliferation was observed after tube cuff and wire vascular
      injury. The number of protease-activated receptor-1-positive (PAR-1-positive)
      cells was increased in the thickened vascular wall of HCII(+/-) mice, suggesting
      enhanced thrombin action in this region. Cuff injury also increased the
      expression levels of inflammatory cytokines and chemokines in the vascular wall
      of HCII(+/-) mice. The intimal hyperplasia in HCII(+/-) mice with vascular injury
      was abrogated by human HCII supplementation. Furthermore, HCII deficiency caused
      acceleration of aortic plaque formation with increased PAR-1 expression and
      oxidative stress in apoE-KO mice. These results demonstrate that HCII protects
      against thrombin-induced remodeling of an injured vascular wall by inhibiting
      thrombin action and suggest that HCII is potentially therapeutic against
      atherosclerosis without causing coagulatory disturbance.

PMID- 17549255
TI  - Mutation in the key enzyme of sialic acid biosynthesis causes severe glomerular
      proteinuria and is rescued by N-acetylmannosamine.
AB  - Mutations in the key enzyme of sialic acid biosynthesis, uridine diphospho-N
      acetylglucosamine 2-epimerase/N-acetylmannosamine (ManNAc) kinase (GNE/MNK),
      result in hereditary inclusion body myopathy (HIBM), an adult-onset, progressive
      neuromuscular disorder. We created knockin mice harboring the M712T Gne/Mnk
      mutation. Homozygous mutant (Gne(M712T/M712T)) mice did not survive beyond P3. At
      P2, significantly decreased Gne-epimerase activity was observed in
      Gne(M712T/M712T) muscle, but no myopathic features were apparent. Rather,
      homozygous mutant mice had glomerular hematuria, proteinuria, and podocytopathy.
      Renal findings included segmental splitting of the glomerular basement membrane,
      effacement of podocyte foot processes, and reduced sialylation of the major
      podocyte sialoprotein, podocalyxin. ManNAc administration yielded survival beyond
      P3 in 43% of the Gne(M712T/M712T) pups. Survivors exhibited improved renal
      histology, increased sialylation of podocalyxin, and increased Gne/Mnk protein
      expression and Gne-epimerase activities. These findings establish this
      Gne(M712T/M712T) knockin mouse as what we believe to be the first genetic model
      of podocyte injury and segmental glomerular basement membrane splitting due to
      hyposialylation. The results also support evaluation of ManNAc as a treatment not
      only for HIBM but also for renal disorders involving proteinuria and hematuria
      due to podocytopathy and/or segmental splitting of the glomerular basement
      membrane.

PMID- 17549256
TI  - Sustained hippocampal IL-1 beta overexpression mediates chronic neuroinflammation
      and ameliorates Alzheimer plaque pathology.
AB  - Neuroinflammation is a conspicuous feature of Alzheimer disease (AD) pathology
      and is thought to contribute to the ultimate neurodegeneration that ensues. IL-1
      beta has emerged as a prime candidate underlying this response. Here we describe
      a transgenic mouse model of sustained IL-1 beta overexpression that was capable
      of driving robust neuroinflammation lasting months after transgene activation.
      This response was characterized by astrocytic and microglial activation in
      addition to induction of proinflammatory cytokines. Surprisingly, when triggered
      in the hippocampus of the APPswe/PS1dE9 mouse model of AD, 4 weeks of IL-1 beta
      overexpression led to a reduction in amyloid pathology. Congophilic plaque area
      fraction and frequency as well as insoluble amyloid beta 40 (A beta 40) and A
      beta 42 decreased significantly. These results demonstrate a possible adaptive
      role for IL-1 beta-driven neuroinflammation in AD and may help explain recent
      failures of antiinflammatory therapeutics for this disease.

PMID- 17549257
TI  - The hypoxia-inducible factor alpha pathway couples angiogenesis to osteogenesis
      during skeletal development.
AB  - Skeletal development and turnover occur in close spatial and temporal association
      with angiogenesis. Osteoblasts are ideally situated in bone to sense oxygen
      tension and respond to hypoxia by activating the hypoxia-inducible factor alpha
      (HIF alpha) pathway. Here we provide evidence that HIF alpha promotes
      angiogenesis and osteogenesis by elevating VEGF levels in osteoblasts. Mice
      overexpressing HIF alpha in osteoblasts through selective deletion of the von
      Hippel-Lindau gene (Vhl) expressed high levels of Vegf and developed extremely
      dense, heavily vascularized long bones. By contrast, mice lacking Hif1a in
      osteoblasts had the reverse skeletal phenotype of that of the Vhl mutants: long
      bones were significantly thinner and less vascularized than those of controls.
      Loss of Vhl in osteoblasts increased endothelial sprouting from the embryonic
      metatarsals in vitro but had little effect on osteoblast function in the absence
      of blood vessels. Mice lacking both Vhl and Hif1a had a bone phenotype
      intermediate between those of the single mutants, suggesting overlapping
      functions of HIFs in bone. These studies suggest that activation of the HIF alpha
      pathway in developing bone increases bone modeling events through cell
      nonautonomous mechanisms to coordinate the timing, direction, and degree of new
      blood vessel formation in bone.

PMID- 17549258
TI  - Antigen-specific immune responses to influenza vaccine in utero.
AB  - Initial immune responses to allergens may occur before birth, thereby modulating
      the subsequent development of atopy. This paradigm remains controversial,
      however, due to the inability to identify antigen-specific T cells in cord blood.
      The advent of MHC tetramers has revolutionized the detection of antigen-specific
      T cells. Tetramer staining of cord blood after CMV infection has demonstrated
      that effective CD8(+) antigen-specific immune responses can follow intrauterine
      viral infections. We hypothesized that sensitization to antigens occurs in utero
      in humans. We studied cord blood B and T cell immune responses following
      vaccination against influenza during pregnancy. Anti-Fluzone and anti-matrix
      protein IgM antibodies were detected in 38.5% (27 of 70) and 40.0% (28 of 70),
      respectively, of cord blood specimens. Using MHC tetramers, HA-specific CD4(+) T
      cells were detected among 25.0% (3 of 12) and 42.9% (6 of 14) of cord blood
      specimens possessing DRB1*0101 and DRB1*0401 HLA types, respectively, and were
      detected even when the DRB1 HLA type was inherited from the father. Matrix
      protein-specific CD8(+) T cells were detected among 10.0% (2 of 20) of HLA
      A*0201(+) newborns. These results suggest that B and T cell immune responses
      occur in the fetus following vaccination against influenza and have important
      implications for determining when immune responses to environmental exposures
      begin.

PMID- 17549260
TI  - In the palace of the sultan: 2007 American Society for Clinical Investigation
      Presidential Address.

PMID- 17549259
TI  - Adiponectin deficiency increases leukocyte-endothelium interactions via
      upregulation of endothelial cell adhesion molecules in vivo.
AB  - This study reports on what we believe are novel mechanism(s) of the vascular
      protective action of adiponectin. We used intravital microscopy to measure
      leukocyte-endothelium interactions in adiponectin-deficient (Ad(-/-)) mice and
      found that adiponectin deficiency was associated with a 2-fold increase in
      leukocyte rolling and a 5-fold increase in leukocyte adhesion in the
      microcirculation. Measurement of endothelial NO (eNO) revealed that adiponectin
      deficiency drastically reduced levels of eNO in the vascular wall.
      Immunohistochemistry demonstrated increased expression of E-selectin and VCAM-1
      in the vascular endothelium of Ad(-/-) mice. Systemic administration of the
      recombinant globular adiponectin domain (gAd) to Ad(-/-) mice significantly
      attenuated leukocyte-endothelium interactions and adhesion molecule expression in
      addition to restoring physiologic levels of eNO. Importantly, prior
      administration of gAd also protected WT mice against TNF-alpha-induced leukocyte
      endothelium interactions, indicating a pharmacologic action of gAd.
      Mechanistically, blockade of eNOS with N(omega)-nitro-L-arginine methyl ester ( L
      NAME) abolished the inhibitory effect of gAd on leukocyte adhesion, demonstrating
      the obligatory role of eNOS signaling in the antiinflammatory action of gAd. We
      believe this is the first demonstration that gAd protects the vasculature in vivo
      via increased NO bioavailability with suppression of leukocyte-endothelium
      interactions. Overall, we provide evidence that loss of adiponectin induces a
      primary state of endothelial dysfunction with increased leukocyte-endothelium
      adhesiveness.

PMID- 17549261
TI  - Analysis of the time-resolved FTIR spectra produced by the photolysis of alkyl
      phenylglyoxylates.
AB  - The photochemistry of alkyl phenylglyoxylates (APG) was further investigated
      using time-resolved infrared spectroscopy. The primary focus was on the analysis
      of weak transient bands around 1828 and 1730 cm(-1) in the time-resolved FTIR
      spectra of glyoxylates. The observed transients were assigned to benzoyl and
      alkyl mandelate ester radicals, respectively. The formation of benzoyl radical
      was fast and attributed to the Norrish Type I process. In addition, the
      intensities of the strong FTIR bands around 1680 and 2100 cm(-1) were used to
      analyze the yields of the triplet state and ketene, respectively. These new and
      previous data on APG photochemistry are discussed in relation to the acrylate
      polymerization photoinitiation by alkyl phenylglyoxylates.

PMID- 17549262
TI  - Single molecule fluorescence spectroscopy of pH sensitive oligonucleotide
      switches.
AB  - Several authors demonstrated that an oligonucleotide based pH-sensitive construct
      can act as a switch between an open and a closed state by changing the pH. To
      validate this process, specially designed fluorescence dye-quencher substituted
      oligonucleotide constructs were developed to probe the switching between these
      two states. This paper reports on bulk and single molecule fluorescence
      investigations of a duplex-triplex pH sensitive oligonucleotide switch. On the
      bulk level, only a partial quenching of the fluorescence is observed, similarly
      to what is observed for other published switches and is supposed to be due to
      intermolecular interactions between oligonucleotide strands. On the single
      molecule level, each DNA-based nanometric construct shows a complete switching.
      These observations suggest the tendency of the DNA construct to associate at high
      concentration.

PMID- 17549263
TI  - Comparative characterization of the efficiency and cellular pharmacokinetics of
      Foscan- and Foslip-based photodynamic treatment in human biliary tract cancer
      cell lines.
AB  - Due to the poor prognosis and limited management options for perihilar
      cholangiocarcinoma (CC) the development of alternatives for treatment is an
      important topic. Photodynamic therapy (PDT) with porfimer as palliative or
      neoadjuvant endoscopic treatment of non-resectable perihilar CC has improved
      quality of life and survival time, but cannot eradicate the primary tumors
      because of inadequate tumoricidal depth (4 mm only around the tumor stenoses).
      The use of meta-tetrahydroxyphenyl chlorin (mTHPC) and photoactivation at higher
      wavelengths (650-660 nm) provides high tumoricidal depth (10 mm) for PDT of
      pancreatic cancer and should yield similar tumoricidal depth in CC. This study
      investigates the photodynamic characteristics of mTHPC in solvent-based
      formulation (Foscan) and in liposomal (water soluble) formulation (Foslip) in an
      in vitro model system consisting of two biliary cancer cell lines (GBC, gall
      bladder cancer and BDC, bile duct cancer cells). Dark toxicity, photodynamic
      efficiency, time-dependent uptake and retention and intracellular localization of
      Foscan and Foslip were studied. The results prove mTHPC as a potent
      photosensitizing agent with high phototoxic potential in biliary cancer cells as
      a concentration of 600 ng ml(-1) and irradiation with 1.5 J cm(-2) (660 +/- 10
      nm) is sufficient for about 90% cell killing. Addition of foetal bovine serum
      (FBS) to the incubation medium and analysis of the uptake and phototoxic
      properties reveals that both photosensitizer formulations bind to serum protein
      fractions, i.e. no difference between Foscan and Foslip can be found in the
      presence of FBS. Laser scanning fluorescence microscopy indicates a similar
      pattern of perinuclear localization of both sensitizers. This study demonstrates
      the potential of mTHPC for treatment of bile duct malignancies and provides
      evidence that Foslip is an equivalent water-soluble formulation of mTHPC that
      should ease intravenous application and thus clinical use of mTHPC.

PMID- 17549264
TI  - Involvement of NADPH oxidase in sulfur dioxide-induced oxidative stress in plant
      cells.
AB  - Bisulfite, a major form of SO2 in aqueous phase of apoplast, may reduce
      photosynthesis rate and thereby crop yield through inducing reactive oxygen
      species (ROS). In this study, ROS production was directly detected in a living
      cell of leaf of spinach (Spinacia oleracea L.) using laser scanning confocal
      microscopes with the assistance of the fluorescence probe dichlorofluorescin
      diacetate (H2DCF-DA). Results showed that, under bisulfite stress, a large
      quantity of ROS indicated by DCF fluorescence was produced in epidermic tissue.
      The role of plasma membrane (PM) NADPH oxidase in bisulfite-induced ROS
      production was also investigated. Treatment with bisulfite resulted in a
      significant increase in the content of ROS and the activity of PM NADPH oxidase
      in spinach leaves. The effects caused by bisulfite were inhibited pronouncedly by
      pretreatment with two widely used NADPH oxidase inhibitors (diphenyleneiodonium
      and quinacrine). Moreover, the change patterns of the bisulfite-induced increase
      and inhibitor-caused decrease in the two parameters were quite similar.
      Additionally, only a small amount of ROS could be observed on in vitro
      chloroplasts under bisulfite stress. Based on all the results, we conclude that
      ROS is involved in bisulfite-induced stress, and the bisulfite-induced
      enhancements in levels of ROS originate mainly from PM NADPH oxidase.

PMID- 17549265
TI  - Rapid and non-invasive detection of plants senescence using a delayed
      fluorescence technique.
AB  - Senescence is a phase of leaf ontogeny marked by declining photosynthetic
      activity that is paralleled by a decline in chloroplast function. The photosystem
      II in a plant is considered to be the primary site where delayed fluorescence
      (DF) is produced. We report here a simple, rapid, and non-invasive technique for
      detecting plants senescence based on quantitative measurements of DF. In the
      experimental study, various senescence symptoms induced by age or hormones were
      examined in the Catharanthus roseus L. G. Don plants. Detecting the DF emissions
      from leaves with a home-made DF biosensor enables DF parameters of C. roseus to
      be produced in a short time. Meanwhile, evaluations of leaves senescence were
      made from measurements of chlorophyll content, ion leakage, and net
      photosynthesis rate (Pn) based on the consumption of CO2 in the tested plants.
      The results of our investigation demonstrate that the changes in DF intensity of
      green plants can truly reflect the changes in photosynthetic capacity and
      chlorophyll content during age-dependent and hormone-modulated senescence.
      Moreover, the DF intensity negatively correlates with ion leakage in both types
      of senescence. With proper calibration, DF may provide an important approach for
      monitoring senescence process in vivo and quantitatively evaluating senescence
      extent. Therefore, a DF technique could be potentially useful for less time
      consuming and automated screening of the interesting mutants with genetic
      modifications that change the plant senescence progress.

PMID- 17549266
TI  - Visible light inactivation of bacteria and fungi by modified titanium dioxide.
AB  - Visible light induced photocatalytic inactivation of bacteria (Escherichia coli,
      Staphylococcus aureus, Enterococcus faecalis) and fungi (Candida albicans,
      Aspergillus niger) was tested. Carbon-doped titanium dioxide and TiO2 modified
      with platinum(IV) chloride complexes were used as suspension or immobilised at
      the surface of plastic plates. A biocidal effect was observed under visible light
      irradiation in the case of E. coli in the presence of both photocatalysts. The
      platinum(IV) modified titania exhibited a higher inactivation effect, also in the
      absence of light. The mechanism of visible light induced photoinactivation is
      briefly discussed. The observed detrimental effect of photocatalysts on various
      microorganism groups decreases in the order: E. coli > S. aureus approximately E.
      faecalis>>C. albicans approximately A. niger. This sequence results most probably
      from differences in cell wall or cell membrane structures in these microorganisms
      and is not related to the ability of catalase production.

PMID- 17549267
TI  - Photobiological and thermal effects of photoactivating UVA light doses on cell
      cultures.
AB  - While near-ultraviolet light has been widely used to photoactivate fluorophores
      and caged compounds in cells, little is known of the long-term biological effects
      of this light. UVA (315-400 nm) photoactivating light has been well characterized
      in short-term cell studies and is now being employed in higher doses to control
      longer-duration phenomena (e.g. gene expression). Annexin V-Cy5/propidium iodide
      apoptosis flow cytometry assays were used to determine responses of HeLa cells to
      doses of UVA light up to 23.85 J cm(-2). Cells seeded at low densities had higher
      percentages of apoptosis and necrosis and were also more susceptible to UVA
      damage than cells seeded at higher densities. The dose to induce apoptosis and
      death in 50% of the cells (dose(1/2)) was determined for two different
      commercially available UVA light sources: 7.6 J cm(-2) for the GreenSpot
      photocuring system and 2.52 J cm(-2) for the BlakRay lamp. All BlakRay doses
      tested had significant cellular responses, whereas no significant cellular
      responses were found for doses below 1.6 J cm(-2) from the GreenSpot light
      source. A temperature control and measurement system was used to determine direct
      heating from the UVA sources and also the effect that cooling cell cultures
      during photoexposure has on minimizing cell damage. Cooling during the BlakRay
      photoexposure significantly reduced the percentage of necrotic cells, but there
      was no significant difference for cooling during photoactivation with the
      GreenSpot. Differences in cell responses to similar UVA doses of different
      intensities suggest that photoduration should be considered along with total dose
      and thermal conditions in photoactivation studies.

PMID- 17549268
TI  - Synthesis, photophysical and photochemical studies of new water-soluble
      indium(III) phthalocyanines.
AB  - The preparation of water-soluble indium(III)phthalocyanine complexes is described
      for the first time in this study. Peripherally and non-peripherally 3
      hydroxypyridine tetrasubstituted indium(III) phthalocyanines (5a, 6a) and their
      quaternarized derivatives (5b, 6b) have been synthesized and characterized by
      elemental analysis, IR, 1H NMR spectroscopy, electronic spectroscopy and mass
      spectra. The quaternarized compounds (5b, 6b) show excellent solubility in water,
      which makes them potential photosensitizers for use in photodynamic therapy (PDT)
      applications. Photochemical and photophysical measurements were conducted on 3
      pyridyloxy appended indium(III) phthalocyanines in dimethylsulfoxide (DMSO) for
      non-ionic (5a, 6a) and in both DMSO and water for quaternarized (5b, 6b)
      derivatives. General trends are described for quantum yields of photodegradation,
      fluorescence lifetimes, fluorescence quantum yields, triplet lifetimes and
      triplet quantum yields as well as singlet oxygen quantum yields of these
      compounds. The singlet oxygen quantum yields (Phi(Delta)), which give an
      indication of the potential of the complexes as photosensitizers in applications
      where singlet oxygen is required (Type II mechanism) are very high (Phi(Delta) >
      0.55). Thus, these complexes may be useful as Type II photosensitizers.

PMID- 17549269
TI  - Experimental study of the excited-state properties and photostability of the
      mycosporine-like amino acid palythine in aqueous solution.
AB  - Characterization of the excited states of the mycosporine-like amino acid
      palythine (lambda(max) = 320 nm) in aqueous solutions was achieved
      experimentally. The low value for the photodegradation quantum yield, (1.2 +/-
      0.2) x 10(-5), confirms that palythine is highly photostable in air saturated
      aqueous solutions. Laser flash photolysis of acetone in the presence of palythine
      allowed for the observation of a transient spectrum which is consistent with the
      triplet-triplet absorption of palythine. Kinetic treatment of the transient
      signals yields a lifetime of the triplet state of ca. 9 micros and a triplet
      energy around 330 kJ mol(-1). The photoacoustic calorimetry results are
      consistent with non-radiative decay as the major fate of excited palythine. A
      comparison of the photodegradation quantum yields and photophysical properties of
      palythine with those previously determined for the other mycosporine-like amino
      acids, shinorine and porphyra-334, suggests that geometrical isomerization around
      the C=N bond may contribute to the rapid deactivation of this group of molecules.

PMID- 17549270
TI  - Determination of the triplet state energies of a series of conjugated porphyrin
      oligomers.
AB  - We report a systematic study of the photophysical parameters relevant to
      photodynamic therapy (PDT) by a new type of sensitizers, conjugated porphyrin
      oligomers. Due to the strong nonlinear properties of oligomers containing 2, 4
      and 8 porphyrin units, these molecules are attractive candidates for PDT via
      multiphoton excitation. The triplet state energy levels for all molecules have
      been determined by the triplet quenching method, phosphorescence measurements and
      DFT calculations. We find that the triplet energies of all the oligomers are
      sufficient to generate singlet oxygen, >94 kJ mol(-1). However, low singlet
      oxygen quantum yields are observed for the tetramer and the octamer, as compared
      to the conjugated dimer and monomeric porphyrin, reflecting the decrease in
      triplet yield. Thus the conjugated porphyrin dimer is the most promising core
      structure for PDT applications via multiphoton excitation.

PMID- 17549271
TI  - Recognition of various biomolecules by the environment-sensitive spectral
      responses of hypocrellin B.
AB  - In this work, the spectral responses of hypocrellin B (HB) to the
      microenvironments of various biomolecules were studied, with human serum albumin
      (HSA), bovine serum albumin (BSA) and ovalbumin (OVA) used as the models for
      proteins, sodium alginate (SOA) and hyaluronan (HYA) for polysaccharides and
      liposomes for lipid membranes. Generally, compared to those in aqueous solution,
      the absorbance and fluorescence of HB were all strengthened in the model systems
      except for the fluorescence in HYA. Specially, according to the spectral
      responses of HB, the microenvironments in biomolecules and liposomes could be set
      in a sequence of hydrophobic grades, i.e., liposomes > proteins >
      polysaccharides. Further, R(F/A), a parameter defined as the ratio of the
      fluorescence intensity to the absorbance, was proposed to identify the
      microenvironment quantitatively. It was found that the R(F/A) could not only
      distinguish various types of biomolecules but also identify specific binding from
      nonspecific binding to proteins or polysaccharides.

PMID- 17549272
TI  - Rapid determination of spore chemistry using thermochemolysis gas chromatography
      mass spectrometry and micro-Fourier transform infrared spectroscopy.
AB  - Spore chemistry is at the centre of investigations aimed at producing a proxy
      record of harmful ultraviolet radiation (UV-B) through time. A biochemical proxy
      is essential owing to an absence of long-term (century or more) instrumental
      records. Spore cell material contains UV-B absorbing compounds that appear to be
      synthesised in variable amounts dependent on the ambient UV-B flux. To facilitate
      these investigations we have developed a rapid method for detecting variations in
      spore chemistry using combined thermochemolysis gas chromatography-mass
      spectrometry and micro-Fourier transform infrared spectroscopy. Our method was
      tested using spores obtained from five populations of the tropical lycopsid
      Lycopodium cernuum growing across an altitudinal gradient (650-1981 m a.s.l.) in
      S.E. Asia with the assumption that they experienced a range of UV-B radiation
      doses. Thermochemolysis and subsequent pyrolysis liberated UV-B pigments (ferulic
      and para-coumaric acid) from the spores. All of the aromatic compounds liberated
      from spores by thermochemolysis and pyrolysis were active in UV-B protection. The
      various functional groups associated with UV-B protecting pigments were rapidly
      detected by micro-FTIR and included the aromatic C[double bond, length as m
      dash]C absorption band which was exclusive to the pigments. We show increases in
      micro-FTIR aromatic absorption (1510 cm(-1)) with altitude that may reflect a
      chemical response to higher UV-B flux. Our results indicate that rapid chemical
      analyses of historical spore samples could provide a record ideally suited to
      investigations of a proxy for stratospheric O3 layer variability and UV-B flux
      over historical (century to millennia) timescales.

PMID- 17549273
TI  - Photocatalytic reduction of carbon dioxide using sol-gel derived titania
      supported CoPc catalysts.
AB  - CoPc loaded titania was synthesized by an improved sol-gel method using a
      homogeneous hydrolysis technique. The grain size of TiO2 and CoPc-TiO2 was
      uniform and average diameters were less than 20 nm. Both catalysts had two
      crystal phases, of which rutile accounted for about 28%. When they were used for
      the photoreduction of CO2 in NaOH solution under ambient conditions, the formate
      yield was significantly higher than that of the others, such as formaldehyde,
      methanol and so on. In order to increase the activity of the photocatalysts some
      factors were optimized, including the quantity of CoPc-TiO2 catalyst,
      concentration of Na(2)SO(3) hole scavenger, concentration of the NaOH solution
      and irradiation time. Under the optimal conditions, the gross photocatalytic
      reduction of CO2 was 1032 micromol (g cat)(-1). Furthermore, the yield of CH4 did
      not increase in the presence of CH(3)OH or HCHO, showing that the generation of
      CH4 from CO2 did not proceed via methanol as an intermediate under these
      conditions.

PMID- 17549274
TI  - Neuro-oncology at the crossroads.

PMID- 17549275
TI  - Multivoxel MR spectroscopic imaging--distinguishing intracranial tumours from non
      neoplastic disease.
AB  - INTRODUCTION: Multi-voxel MR spectroscopic imaging (MRSI) provides chemical
      metabolite information that can supplement conventional MR imaging in the study
      of intracranial neoplasia. Our purpose was to use a robust semi-automated
      spectroscopic analysis to distinguish intracranial tumours from non-neoplastic
      disease. MATERIALS AND METHODS: Twenty intracranial tumours and 15 patients with
      non-neoplastic disease confirmed on histological examination or serial
      neuroimaging were studied with 2-dimensional MRSI using point-resolved
      spectroscopic (PRESS) imaging localisation. Using semi-automated post-processing
      software, spectra were analysed for peak heights of choline (Cho), creatine (Cr),
      N-acetyl aspartate (NAA), lactate (Lac) and lipid (Lip). Normalised Cho (nCho)
      ratios, computed by dividing maximum Cho in the lesion by the normal-appearing
      brain, were compared between intracranial tumours and non-neoplastic disease.
      RESULTS: Meningiomas displayed homogeneously elevated Cho. Malignant tumours,
      especially large glioblastoma multiforme, displayed inhomogeneity of metabolites
      within the tumour. All tumours had elevation of nCho >1 (mean 1.91 +/- 0.65), and
      non-neoplastic diseases had tumour nCho <1 (mean 0.91 +/- 0.46), which was
      significantly lower (P <0.05). Two patients with non-neoplastic lesions, one with
      subacute cerebral infarction and the other with cryptococcoma, had elevated Cho
      compared to normal tissue (false positive rate 13%). CONCLUSION: Using semi
      automated MRSI method, a simplified normalised Cho algorithm provides a method to
      distinguish intracranial tumours from non-neoplastic disease.

PMID- 17549276
TI  - Epidemiology, management and treatment outcome of medulloblastoma in singapore.
AB  - INTRODUCTION: Medulloblastoma/primitive neuroectodermal tumour is the most common
      type of malignant brain tumour in children. Long-term survival rates have
      improved over the years with a combination of surgical, radiotherapeutic and
      chemotherapeutic treatment modalities in the developed world. This paper aims to
      analyse the epidemiology and outcome of medulloblastoma in Singapore and compare
      our results with those reported in the literature. MATERIALS AND METHODS: A 9
      year retrospective study was done using data reported to the Singapore Children's
      Cancer Registry from June 1997 to June 2005. Only 39 children up to the age of 15
      years diagnosed histologically with medulloblastoma or primitive neuroectodermal
      tumour arising from the cerebellum were included in the study. Follow-up data
      were collected up to June 2006 and analysed using SPSS v 13.0 software. RESULTS:
      Medulloblastoma/primitive neuroectodermal tumour was the most common type of
      brain tumour, accounting for 40.7% of all brain tumours diagnosed in children in
      Singapore. The 5-year event-free survival rate was 44.5%, while the 5- year
      overall survival rate was 51.5%. Nearly half (41%) of our patients had spinal
      metastasis at presentation and this was associated with a worse event-free
      survival (6.3% vs 71.9%, P = 0). Children under 36 months of age had a
      significantly poorer overall survival (28.8% vs 52.2%, P = 0.041). CONCLUSIONS:
      The outcome of medulloblastoma in Singapore was inferior to reported figures in
      the literature. We need to close identified gaps in care, like standardising
      assessment and treatment protocols, in order to improve our results. Research
      into molecular and genetic characteristics may also throw light on whether the
      disease is inherently more aggressive in our population.

PMID- 17549277
TI  - Anaesthetic management of awake craniotomy for tumour resection.
AB  - INTRODUCTION: Awake craniotomy allows accurate localisation of the eloquent
      brain, which is crucial during brain tumour resection in order to minimise risk
      of neurologic injury. The role of the anaesthesiologist is to provide adequate
      analgesia and sedation while maintaining ventilation and haemodynamic stability
      in an awake patient who needs to be cooperative during neurological testing. We
      reviewed the anaesthetic management of patients undergoing an awake craniotomy
      procedure. MATERIALS AND METHODS: The records of all the patients who had an
      awake craniotomy at our institution from July 2004 till June 2006 were reviewed.
      The anaesthesia techniques and management were examined. The perioperative
      complications and the outcome of the patients were noted. RESULTS: There were 17
      procedures carried out during the study period. Local anaesthesia with moderate
      to deep sedation was the technique used in all the patients. Respiratory
      complications occurred in 24% of the patients. Hypertension was observed in 24%
      of the patients. All the complications were transient and easily treated. During
      cortical stimulation, motor function was assessed in 16 patients (94%). Three
      patients (16%) had lesions in the temporal-parietal region and speech was
      assessed intraoperatively. Postoperative motor weakness was seen in 1 patient
      despite uneventful intraoperative testing. No patient required intensive care
      unit stay. The median length of stay in the high dependency unit was 1 day and
      the median length of hospital stay was 9 days. There was no in-hospital
      mortality. CONCLUSION: Awake craniotomy for brain tumour excision can be
      successfully performed under good anaesthetic conditions with careful titration
      of sedation. Our series showed it to be a well-tolerated procedure with a low
      rate of complications. The benefits of maximal tumour excision can be achieved,
      leading to potentially better patient outcome.

PMID- 17549278
TI  - Awake craniotomy under local anaesthesia and monitored conscious sedation for
      resection of brain tumours in eloquent cortex--outcomes in 20 patients.
AB  - INTRODUCTION: Resection or even biopsy of an intra-axial mass lesion in close
      relationship to eloquent cortex carries a major risk of neurological deficit. We
      review the safety and effectiveness of craniotomy under local anaesthesia and
      monitored conscious sedation for resection of mass lesions involving eloquent
      cortex. MATERIALS AND METHODS: We performed a 3-year retrospective review of
      patients who underwent awake craniotomy under local anaesthesia at the National
      Neuroscience Institute, Singapore. All patients had tumours in close proximity to
      eloquent cortex, including speech areas in the dominant hemisphere as well as
      primary sensory and motor cortex in either hemisphere. Brain mapping was
      performed by direct cortical stimulation using the Ojemann stimulator to identify
      a safe corridor for surgical approach to the tumour. Intraoperative physiological
      monitoring was carried out by assessment of speech, motor and sensory functions
      during the process of surgical resection. All resections were evaluated and
      verified by postoperative imaging and reviewed by an independent assessor.
      Postoperative complications and neurological deficits, as well as extent of
      tumour resection, were evaluated. RESULTS: A total of 20 patients underwent
      stereotactic resection over a period of 3 years from July 2003 to August 2006.
      There were 7 male patients and 13 female patients, with a mean age of 39.8 years.
      The average length of stay was 5.5 days. There were no major anaesthetic
      complications and no perioperative deaths. Postoperative neurological deficits
      were seen in 6 patients (30%) and this was permanent in only 1 patient (5%). The
      degree of cytoreduction achieved was greater than 90% in 58% of patients and a
      further 21% had greater than 80% cytoreduction. CONCLUSION: Tumour surgery with
      conscious sedation in combination with frameless computer stereotactic guidance
      is a safe technique that allows maximal resection of lesions in close
      relationship to eloquent cortex and has a low risk of neurological deficit.

PMID- 17549279
TI  - Optimising radiation therapy techniques for tumours of the central nervous
      system.
AB  - INTRODUCTION: This study aims to assess the early tumour outcome and morbidity
      associated with radiation therapy (RT) in tumours of the central nervous system
      (CNS). MATERIALS AND METHODS: Patients receiving RT with radical intent were
      entered on a prospective database. Tumour types were categorised into glioma,
      base of skull, pituitary, germ cell or primitive neuroectodermal tumour (PNET)
      and other malignant CNS tumours. Study endpoints were overall survival and
      progression free survival. Acute and late toxicity endpoints included Common
      Terminology Criteria version 3.0 (CTC) grade 3 or 4 events, need for admission
      during RT and change in performance status at 12 months. RESULTS: One hundred and
      fifty-two patients with CNS tumours were managed with radical intent over the 4
      year period. The median age was 49 years and 68.4% were Eastern Co-operative
      Group (ECOG) 0-1 performance status. The major pathology groups were glioma
      (59.9%) and base of skull tumours (17.1%). Gross total resection was performed in
      28.3% only and RT was delayed after diagnosis until time of progression in 19.7%.
      For the 91 patients with glioma, the median survival and 2-year survival rate was
      19.1 months and 44.1%, respectively. The 2-year survival rates for the subgroups
      of WHO Grade I or II, III and IV were 100%, 52% and 35%, respectively. For the
      non-glioma tumour groups, the relapse varied with pathology. Toxicity was minimal
      with only 3 acute and 3 late CTC grade 3 or 4 events occurring. Overall, 47 or
      31% of patients required some inpatient hospitalisation during RT, although this
      was determined to have some causative relationship to RT in only 12 or 8% of
      patients. In the 12 months post-RT, performance status was stable or improved in
      76.2% of patients, and most deterioration was associated with tumour relapse.
      CONCLUSIONS: RT for CNS tumours using modern techniques was well-tolerated with
      good tumour outcome and minimal morbidity.

PMID- 17549280
TI  - Improved median survival for glioblastoma multiforme following introduction of
      adjuvant temozolomide chemotherapy.
AB  - INTRODUCTION: The use of adjuvant temozolomide (TMZ) in patients managed with
      surgery and adjuvant radiation therapy (RT) for glioblastoma multiforme (GBM) has
      been demonstrated to improve median and 2-year survival in a recent large
      international multicentre study. To confirm this result in routine clinical
      practice, an audit of the management and outcome of patients with GBM at The
      Cancer Institute Radiation Oncology was performed. MATERIALS AND METHODS: All
      patients with GBM managed radically at The Cancer Institute Radiation Oncology
      from May 2002 to 2006 were entered into a prospective database. Patient, tumour
      and treatment factors were analysed for association with the outcome of median
      survival (MS). Survival was calculated using the Kaplan-Meier technique and
      correlation was assessed using Cox proportional hazards regression. RESULTS:
      Forty-one patients with GBM were managed with radical intent over the 4- year
      period. The median age was 54 years and 66% were Eastern Cooperative Oncology
      Group (ECOG) 0-1 performance status. Macroscopic, subtotal and biopsy alone
      procedures were performed in 61%, 29% and 10% of patients, respectively. The
      median time from surgery to RT was 26 days. Adjuvant TMZ was used in 44% of
      patients (n = 18). The MS of the total group was 13.6 months, with a 24% 2-year
      overall survival. The use of TMZ was associated with improved MS (19.6 versus
      12.8 months; P = 0.035) and improved 2-year survival (43% versus 0%). A
      requirement of dexamethasone dose greater than 4 mg at the end of RT (P = 0.012)
      was associated with worse survival, but there was no association of MS with age,
      ECOG, tumour size or extent of surgery. CONCLUSION: The median and 2-year
      survival outcomes are comparable to the results of the European Multicentre Study
      and justify the continued use of TMZ in routine clinical practice.

PMID- 17549281
TI  - Salvage chemotherapy in progressive high-grade astrocytoma.
AB  - INTRODUCTION: Despite aggressive multidisciplinary interventions, patients with
      high-grade astrocytomas experience tumour progression or recurrence. Treatment
      for this group of patients remains a formidable challenge. We describe our
      experience of salvage chemotherapy for these patients. MATERIALS AND METHODS: A
      retrospective review of relevant clinical and radiographic information of
      patients who received at least one cycle of salvage chemotherapy for progressive
      high-grade astrocytoma at the National Cancer Center, Singapore, from March 2004
      to September 2006, was conducted. Patients underwent regular assessment with
      clinical examination and magnetic resonance brain imaging to gauge response to
      salvage chemotherapy. Survival and progression free interval data were analysed
      via Kaplan-Meier method. RESULTS: Twenty-four patients (13 glioblastomas, 11
      anaplastic astrocytomas) had received chemotherapy as salvage treatment following
      progression of their high-grade astrocytoma. Among 20 patients assessable for
      tumour response, there were 4 patients with partial responses and 9 with stable
      responses. The 12-month survival rate for the entire group from time of onset of
      tumour progression was 49.6%. Eight patients had survived more than 12 months at
      the time of writing. Among patients with glioblastoma, the 12-month survival rate
      was 30% and the median survival was 11.2 months. For patients with anaplastic
      astrocytoma, the 12-month survival rate was 73%. CONCLUSION: Durable disease
      control and prolonged survival were seen in a significant portion of selected
      patients with progressive high-grade astrocytoma who received salvage
      chemotherapy.

PMID- 17549282
TI  - Improvements in quality of care resulting from a formal multidisciplinary tumour
      clinic in the management of high-grade glioma.
AB  - INTRODUCTION: There is increasing belief that a formal protocol-based
      multidisciplinary care model should be adopted as an optimal care model in
      oncology. However, there is minimal outcome evidence to demonstrate an
      improvement in patient care. The aim of this study was to compare clinical
      quality outcomes between patients with high-grade glioma managed at one hospital
      using a formal neuro-oncology multidisciplinary tumour clinic (MTC) and a second
      hospital with a traditional on-call referral pattern (non-MTC). MATERIALS AND
      METHODS: Patients with high-grade glioma managed radically with radiation therapy
      at 2 Singapore hospitals from May 2002 to May 2006 were entered into a
      prospective database. Patients were grouped into management via MTC or non-MTC.
      Four clinical quality indicators were chosen retrospectively to assess the
      variation in practice: a) Use of computed tomography (CT) or magnetic resonance
      (MR) imaging post-resection (POI) for assessment of residual disease; b)
      Commencement of radiation therapy (RT) within 28 days of surgery; c) Adjuvant
      chemotherapy use for glioblastoma multiforme (CTGBM) and d) Median survival.
      RESULTS: Sixty-seven patients were managed radically, with 47 by MTC and by 20 by
      non-MTC. MTC patients were more likely to have POI (P = 0.042), and CTGBM (P =
      0.025). Although the RT start time was similar for the whole cohort (60% versus
      45%: P = 0.296); for GBM patients, the RT start was earlier (63% vs 33% P =
      0.024). The median survival for the MTC group was 18.7 months versus 11.9 months
      for the non-MTC group (P = 0.11). CONCLUSION: Clinical quality outcomes were
      significantly improved in patients with high-grade glioma managed in this neuro
      oncology MTC.

PMID- 17549283
TI  - Insights into the cancer stem cell model of glioma tumorigenesis.
AB  - Not all cancer cells are born equal. While the great majority of the cells that
      make up tumours are destined to differentiate, albeit aberrantly, and eventually
      stop dividing, a handful of cancer cells appear to possess limitless replicative
      potential. This review presents compelling evidence to suggest that the bulk of
      malignant cells of most cancers are generated by a rare fraction of stem cell
      like cancer cells. These cells, dubbed cancer stem cells, are phenotypically
      similar to the normal stem cells of the corresponding tissue of origin, but they
      exhibit dysfunctional patterns of self-renewal and differentiation. Cancer stem
      cells that are capable of recapitulating brain tumours as xenografts in mice are
      characterised by defined stem cell markers. These brain tumour stem cells
      demonstrate enhanced chemoresistance and radioresistance mechanisms compared to
      non-stem cells in the heterogeneous tumour, which suggest that they may be the
      likely candidates for tumour progression and recurrence. Indeed, recent work has
      shown that such aberrant signalling pathways may be targeted in novel anti-cancer
      therapeutic strategies. The stem cell concept of tumour progression prompts
      immediate attention to a new paradigm in cancer research with a focus on this
      minority subset of cells, and the design of novel therapeutic strategies to
      target these cells that are insignificant within the population of tumour cells,
      but that are in fact the relevant cells to be destroyed.

PMID- 17549284
TI  - The role of surgery in high-grade glioma--is surgical resection justified? A
      review of the current knowledge.
AB  - INTRODUCTION: The aims of this article were to review the role of surgical
      resection in the management of high-grade gliomas and to determine whether there
      is any survival benefit from surgical resection. METHODS: A literature review of
      the influence of surgical resection on outcome was carried out. Relevant original
      and review papers were obtained through a PubMed search using the following
      keywords: glioma, resection, prognosis and outcome. RESULTS: Presently, there is
      a lack of evidence to support a survival benefit with aggressive glioma
      resection, but this should not detract patients from undergoing surgery as there
      are many other clinical benefits of glioma excision. In addition, limiting
      surgical morbidity through the use of adjuvant techniques such as intraoperative
      magnetic resonance imaging (MRI), functional MRI and awake craniotomy is becoming
      increasingly important. CONCLUSIONS: Ideally, a randomised controlled trial would
      be the best way to resolve the issue of whether (and to what extent) surgical
      resection leads to improvements in patient outcome and survival, but this would
      not be ethical. The second best option would be well-controlled retrospective
      studies with a multivariate analysis of all potential confounding factors.

PMID- 17549285
TI  - Chemotherapy in adults with gliomas.
AB  - Treating patients with gliomas requires a multidisciplinary approach, which often
      includes surgery, radiation and chemotherapy. Recent developments have
      demonstrated the efficacy of chemotherapeutic agents in patients with newly
      diagnosed or recurrent gliomas. Large clinical studies have provided important
      information on the impact of chemotherapy for anaplastic oligodendrogliomas in
      the upfront setting. Randomised trials have demonstrated the benefit of
      chemoradiation for patients with glioblastoma. Investigations are also under way
      to clarify the role of chemotherapy for low-grade gliomas. This review article
      summarises the recent developments and approaches in the use of chemotherapy to
      treat adult patients with astrocytomas and oligodendrogliomas.

PMID- 17549286
TI  - Association between the plasminogen activator inhibitor-1 4G/5G polymorphism and
      venous thrombosis. A meta-analysis.
AB  - The effect of the 675 insertion/deletion (4G/5G) polymorphism of plasminogen
      activator inhibitor-1 (PAI-1) gene on the risk of venous thromboembolism (VTE)
      remains controversial. In this study, we performed a meta-analysis of published
      data regarding this issue. A comprehensive electronic search was carried out up
      until September 2006. A total of 22 articles were included in the analysis that
      was performed using random effects models. Eighteen papers, concerning patients
      without another known risk factor, comprised 2,644 cases and 3,739 controls. The
      alleles contrast (4G vs. 5G allele) yielded a statistically significant odds
      ratio (OR) of 1.153 (95% confidence interval [CI]: 1.068-1.246). In a sub
      analysis of five studies that included 256 cases with another genetic risk factor
      and 147 controls, the combined per-allele OR was still significant (OR: 1.833,95%
      CI: 1.325-2.536). On the contrary, the analysis of five studies regarding cases
      with a non-genetic risk factor for VTE (antiphospholipid antibody syndrome,
      Behcet disease) provided insignificant results in all aspects. There was no
      evidence for heterogeneity and publication bias in all analyses. Based on our
      findings, the 4G allele appears to increase the risk of venous thrombosis,
      particularly in subjects with other genetic thrombophilic defects. Recommendation
      for detection of this polymorphism in evaluating thrombophilia in such patients
      might be considered.

PMID- 17549287
TI  - Vasa vasorum and atherosclerosis - Quid novi?
AB  - The role of vasa vasorum (VV) in atherosclerosis is hotly debated, and new
      experimental techniques have recently opened an opportunity to take a fresh look
      at this important topic. Although the proliferation of VV due to atherogenic
      stimuli is controversial, experimental and clinical evidence strongly suggest the
      potential of VV in vascular proliferative disorders. In the past, paradigms of
      atherosclerosis and restenosis have excluded the adventitia and VV in the artery
      wall due, in part, to a lack of i) appropriate animal models featuring
      adventitial VV neovascularization, ii) imaging technologies to quantitate
      adventitial VV and plaque neovascularization and iii) its consequences,
      concerning information on detectable plaque substrate in vulnerable lesions. VV
      proliferation is associated with increasing plaque burden and is linked to
      cellular processes which are critical during the development of atherosclerotic
      plaques such as inflammation, plaque perfusion and concomitant intraplaque
      hemorrhage - but the regulation and induction of VV based on pathological
      settings are poorly understood. This review discusses the current scientific
      status and its controversies and identifies open research questions.

PMID- 17549288
TI  - Circulating P-selectin and the risk of recurrent venous thromboembolism.
AB  - The clinical relevance of high P-selectin levels in venous thrombosis is unknown.
      We prospectively followed 544 patients with first unprovoked venous
      thromboembolism (VTE) after cessation of anticoagulation and evaluated P-selectin
      as a risk factor of recurrent VTE. VTE recurred in 63 (12%) patients. Patients
      with recurrence had significantly higher P-selectin levels than those without
      (45.8 mg/dl +/- 16.4 vs. 40.1 mg/dl +/- 13.3; p = 0.006). After four years, the
      probability of recurrence was 20.6% (95% confidence interval [CI] 12.6-28.5)
      among patients with P-selectin values above the 75(th) percentile of the patient
      population and was 10.8% (95% CI 7.2-14.3) among patients with lower values (p =
      0.046). Compared to patients with low P-selectin, adjusted risk of recurrence was
      1.7-fold (95% CI 1.0-2.9, p = 0.045) increased among patients with P-selectin
      levels exceeding the 75(th) percentile. We conclude that high circulating P
      selectin is a risk factor of recurrent VTE.

PMID- 17549289
TI  - Characterisation of five factor XI mutations.
AB  - A large scale factor XI (FXI) mutation screening program identified a number of
      novel candidate mutations and previously reported mutations and polymorphisms.
      Five potential missense mutations were selected for further study; these included
      two novel missense mutations - Met-18Ile (p.Met1Ile) and Met102Thr (p.Met120Thr),
      two previously reported missense mutations - Tyr133Ser (Tyr151Ser) and Thr575Met
      (Thr593Met), and one amino acid substitution previously reported as a
      polymorphism - Arg378Cys (Arg396Cys). The substitutions were recreated by the
      site-directed mutagenesis of a FXI cDNA and stably expressed in a BHK-570 cell
      line. Subsequent analysis of both the conditioned media and cell lysates showed
      that three of the substitutions, Met-18Ile, Met102Thr andTyr133Ser, prevented
      secretion of the mutated protein from the transfected cell line, resulting in a
      cross-reactive material negative (CRM-) phenotype. The remaining two mutants,
      Thr575Met and Arg378Cys, secreted significant levels of FXI into the conditioned
      media; however, these mutant FXIs were shown to have negligible factor IX
      activation activity in an APTTbased assay. These results confirmed all five of
      the missense mutations as being causative of factor XI deficiency, despite one
      having been previously reported as a polymorphism (Arg378Cys) and one (Tyr133Ser)
      as a mild mutation - FXI:C 38 U/dl in a homozygous patient.

PMID- 17549290
TI  - Factor XIII activation peptide is released into plasma upon cleavage by thrombin
      and shows a different structure compared to its bound form.
AB  - The first step of coagulation factor XIII (FXIII) activation involves cleavage of
      the FXIII activation peptide (FXIII-AP) by thrombin. However, it is not known
      whether the FXIII-AP is released into plasma upon cleavage or remains attached to
      activated FXIII. The aim of the present work was to study the structure of free
      FXIII-AP, develop an assay for FXIII-AP determination in human plasma, and to
      answer the question whether FXIII-AP is released into plasma. We used ab-initio
      modeling and molecular dynamics simulations to study the structure of free FXIII
      AP. We raised monoclonal and polyclonal antibodies against FXIII-AP and developed
      a highly sensitive and specific ELISA method for direct detection of FXIII-AP in
      human plasma. Structural analysis showed a putative different conformation of the
      free FXIII-AP compared to FXIII-AP bound to the FXIII protein. We concluded that
      it might be feasible to develop specific antibodies against the free FXIII-AP.
      Using our new FXIII-AP ELISA, we found high levels of FXIII-AP in in-vitro
      activated plasma samples and serum. We showed for the first time that FXIIIAP is
      detached from activated FXIII and is released into plasma, where it can be
      directly measured. Our findings may be of major clinical interest in regard to a
      possible new marker in thrombotic disease.

PMID- 17549291
TI  - Calcium-binding sites of the thrombin-thrombomodulin-protein C complex: possible
      implications for the effect of platelet factor 4 on the activation of vitamin K
      dependent coagulation factors.
AB  - The Ca(2+)-dependence of protein C activation by thrombin in complex with
      thrombomodulin (TM) containing chondroitin sulfate (CS) exhibits saturation at
      approximately 0.5-1 mM Ca(2+), but with TM lacking CS, it has a distinct optimum
      at approximately 0.1 mM Ca(2+). Since the substrate protein C has multiple Ca(2+)
      binding sites, and the cofactor TM also interacts with Ca(2+), the basis for
      differences in Ca(2+) effect on protein C activation by thrombin in complex with
      TM containing or lacking CS is not known. In this study, by using full-length and
      Gla-domainless mutants of protein C whose activation by thrombin is independent
      of either Ca(2+) or both Ca(2+) and TM, we demonstrate that i) the Ca(2+)
      occupancy of a high-affinity binding site in TM is essential for the high
      affinity interaction of the cofactor with thrombin, ii) the Ca(2+) occupancy of a
      binding site (K(D) approximately 50 microM) in the catalytic domain of protein C
      is required for the substrate recognition by the thrombin-TM complex, however, at
      this concentration of Ca(2+) the Gla domain of protein C is not folded properly
      and thus interacts with exosite-2 of thrombin in complex with TM that lacks CS
      but not with TM that contains CS, and finally iii) platelet factor 4 can
      nonspecifically interact with the Gla domain of protein C and other coagulation
      factors to influence their activation only at subphysiological concentrations of
      Ca(2+).

PMID- 17549292
TI  - International registry on factor XIII deficiency: a basis formed mostly on
      European data.
AB  - FXIII deficiency is known as one of the rarest blood coagulation disorders. In
      this study, the phenotypic and in part genotypic data of 104 FXIII-deficient
      patients recorded from 1993 - 2005 are presented. The most common bleeding
      symptoms were subcutaneous bleeding (57%) followed by delayed umbilical cord
      bleeding (56%), muscle hematoma (49%), hemorrhage after surgery (40%),
      hemarthrosis (36%), and intracerebral bleeding (34%). Prophylactic treatment was
      initiated in about 70% of all patients. FXIII-B subunit-deficient patients had a
      milder phenotype than patients with FXIII-A subunit deficiency. The most frequent
      mutation affecting the F13A gene was a splice site mutation in intron 5 (IVS5
      1G>A). This mutation was found in eight (17%) of 46 analyzed families. The
      haplotype analysis of patients carrying the IVS5-1A allele was consistent with a
      founder effect. The international registry (http://www.f13-database.de) will
      provide clinicians and scientists working on FXIII deficiency with a helpful tool
      to improve patient care and direct future studies towards better understanding
      and treatment of the disease.

PMID- 17549293
TI  - Comparison of the pharmacokinetics of two von Willebrand factor concentrates
      [Biostate and AHF (High Purity)] in people with von Willebrand disorder. A
      randomised cross-over, multi-centre study.
AB  - Plasma-derived factor concentrates are important in the management of von
      Willebrand disorder (VWD). In our geographic locality, a single viral
      inactivation step concentrate (AHF [High Purity]), has been replaced with one
      using a double viral inactivation step (Biostate). The aim of this study was to
      compare the pharmacokinetics of von Willebrand factor (VWF) and factor VIII
      (FVIII) after administration of AHF (High Purity) and Biostate. This study was a
      single-blind, randomised cross-over, multi-centre investigation in twelve people
      with VWD, comprising four type 3, two type 2B, one type 2M and five type 1 VWD.
      The subjects received a single infusion of 60 IU/kg ristocetin cofactor activity
      (VWF:RCo) of either AHF (High Purity) or Biostate, and after a minimum 15-day
      wash-out period they received the alternative product. Blood samples were
      collected for up to 48 hours after each dose for assay of FVIII coagulant
      activity (FVIII:C) and VWF by VWF:RCo, collagen binding capacity (VWF:CB) and
      antigen (VWF:Ag). As a measure of delivered VWF 'functionality' we calculated the
      area-under-the-concentration-time-curve (AUC) ratios of VWF:RCo to VWF:Ag and
      VWF:CB to VWF:Ag. The effect on platelet adhesiveness by PFA-100 closure times
      (CTs) was measured prior to and 30 minutes post infusion. VWF multimers were also
      assessed pre and post infusion. Pharmacokinetic parameters after AHF (High
      Purity) and Biostate were in close agreement for VWF:RCo (confirming dosing
      equivalence). Parameters for other study markers were also similar, although
      Biostate tended to yield relatively lower VWF:Ag and higher VWF:CB levels.
      Although AHF (High Purity) and Biostate resulted in similar levels of high
      molecular-weight (HMW) multimers post-infusion, the relative level of HMW to low
      molecular-weight (LMW) multimers were determined to be higher following Biostate.
      The relative levels of functional VWF (i.e. VWF:CB and VWF:RCo) to VWF:Ag were
      also higher in Biostate compared to AHF (High Purity). With both study products,
      PFA-100 CTs 30 minutes post infusion showed minor improvement for only some
      subjects. In conclusion, the pharmacokinetics of FVIII:C and VWF are not
      significantly different after administration of AHF (High Purity) and Biostate.
      Study parameters considered as 'in-vitro' markers of VWF 'functionality' or
      potential clinical efficacy (i.e. VWF:CB and VWF:RCo relative to VWF:Ag, level of
      HMW VWF relative to LMW-VWF) were determined to be higher for Biostate than AHF
      (High Purity). PFA-100 CTs did not adequately reflect changes in these VWF
      parameters. Based on these results, one would expect Biostate to be at least as
      effective, if not superior to AHF (High Purity) for the treatment of VWD.

PMID- 17549294
TI  - Rivaroxaban for thromboprophylaxis after orthopaedic surgery: pooled analysis of
      two studies.
AB  - Rivaroxaban (BAY 59-7939) is an oral, direct factor Xa inhibitor in clinical
      development for the prevention and treatment of venous thromboembolism (VTE).
      This analysis of pooled results from two phase II studies of rivaroxaban for VTE
      prevention after major orthopaedic surgery aimed to strengthen the conclusions of
      the individual studies. One study was conducted in patients undergoing total hip
      replacement (THR; N = 722), and one in patients undergoing total knee replacement
      (TKR; N = 621). In both studies, patients were randomized, doubleblind, to oral,
      twice-daily (bid) rivaroxaban beginning after surgery, or subcutaneous enoxaparin
      (40 mg once daily beginning before THR, and 30 mg bid beginning after TKR).
      Treatment continued until mandatory bilateral venography was performed 5-9 days
      after surgery. Total VTE (deep vein thrombosis, pulmonary embolism, and all-cause
      mortality) occurred in 16.1-24.4% of per-protocol patients receiving rivaroxaban
      5-60 mg, and 27.8% receiving enoxaparin (n = 914). There was a flat dose response
      relationship between rivaroxaban and total VTE (p = 0.39). Major bleeding (safety
      population, n = 1,317) increased dose-dependently with rivaroxaban (p < 0.001),
      occurring in 0.9%, 1.3%, 2.1%, 3.9%, and 7.0% of patients receiving rivaroxaban
      total daily doses of 5, 10, 20, 40, and 60 mg, respectively, versus 1.7% of
      patients receiving enoxaparin. No routine coagulation monitoring was performed,
      and there were no significant differences between dose response relationships
      with rivaroxaban after THR and TKR. Overall, rivaroxaban total daily doses of 5
      20 mg had the most favorable balance of efficacy and safety, relative to
      enoxaparin, for the prevention of VTE after major orthopaedic surgery.

PMID- 17549295
TI  - Differential impact of conventional and low-dose oral hormone therapy (HT),
      tibolone and raloxifene on functionality of the activated protein C system.
AB  - Recent studies have shown that hormone therapy (HT) is associated with an
      acquired resistance to activated protein C (APC). The aims of the present study
      were to evaluate a possible dose-response relationship and differential effects
      of different HT regimens on functionality of the APC system. Two hundred two
      healthy women were randomly assigned to receive treatment for 12 weeks with
      tablets containing either low-dose HT containing 1 mg 17ss-oestradiol + 0.5 mg
      norethisterone acetate (NETA) (n = 50), conventional-dose HT containing 2 mg 17ss
      oestradiol and 1 mg NETA (n = 50), 2.5 mg tibolone (n = 51), or 60 mg raloxifene
      (n = 51). Normalized APC system sensitivity ratios (nAPCsr) were determined in
      plasma collected at baseline and after 12 weeks using a thrombin generation-based
      APC resistance test probed with either recombinant APC (rAPC) or thrombomodulin
      (rTM). NAPCsr increased in both the conventional- and low-dose HT groups,
      consistent with reduced sensitivity to APC. The increase was slightly more
      pronounced in the conventional-dose group, but the difference between the two HT
      groups was not statistically significant. The sensitivity to APC was only
      marginally altered in those allocated to tibolone. Consequently, tibolone showed
      a different phenotype as compared with the low-dose HT group. A small increase in
      nAPCsr with both rAPC and rTM was seen in the raloxifene-group, but the increase
      was less than in the low-dose HT group. Our findings indicate that oestrogen
      progestin therapy induces an APC resistant phenotype, which may be related to
      dose, whereas tibolone and raloxifene only marginally alter the sensitivity to
      APC.

PMID- 17549296
TI  - Clinically suspected acute recurrent pulmonary embolism: a diagnostic challenge.
AB  - It is unknown whether strategies validated for diagnosing pulmonary embolism (PE)
      are valid in patients with a history of PE. It was the objective of this study to
      investigate whether a diagnostic algorithm consisting of sequential application
      of a clinical decision rule (CDR), a quantitative D-dimer test and computed
      tomography (CT) safely ruled out a clinical suspicion of acute recurrent PE. Data
      were obtained from a diagnostic outcome study of patients suspected of PE. Acute
      recurrent PE was ruled out by an unlikely probability of PE (CDR score </= 4
      points) combined with a normal D-dimer test (</= 500 ng/ml) or by a normal CT in
      all other patients. The primary outcome was the incidence of acute recurrent
      venous thromboembolism during three months of follow-up in patients with normal
      tests and not treated with anticoagulants. Of 3,306 patients suspected of acute
      PE, 259 patients (7.8%) had a history of PE of whom 234 were not treated with
      anticoagulants. The probability of PE was unlikely in 82 of 234 patients (35%),
      and 42 had a normal D-dimer test (18%), excluding recurrent PE. None of these
      patients had a thrombotic event during follow-up (0%, 95%CI: 0-6.9). A CT was
      indicated in all other patients (192) and ruled out recurrent PE in 127 patients
      (54%). Only one patient with a negative CT had a fatal recurrent PE during follow
      up (0.8%; 95%CI: 0.02-4.3). In conclusion, this prospective study demonstrates
      the safety of ruling out a clinical suspicion of acute recurrent PE by a simple
      diagnostic algorithm in patients with a history of PE.

PMID- 17549297
TI  - Antiphosphatidylethanolamine antibodies are associated with an increased odds
      ratio for thrombosis. A multicenter study with the participation of the European
      Forum on antiphospholipid antibodies.
AB  - A multicenter study was set up to evaluate the prevalence, clinical and
      biological significance of antiphosphatidylethanolamine antibodies (aPE) in
      thrombotic patients with or without the main known clinical and biological risk
      factors for thrombosis. APE and antibodies, defined as the laboratory criteria of
      antiphospholipid syndrome (APS) -lupus anticoagulant, anticardiolipin and anti
      beta(2)-GPI antibodies were measured in 270 patients with thrombosis (234 venous
      and 37 arterial) and 236 matched controls. APE were found in 15% of thrombotic
      patients compared to 3% of controls (p < 0.001) with no predominant isotype, no
      association with the main known clinical or biological risk factors for
      thrombosis neither with a type of thrombosis, arterial or venous. In a
      multivariate logistic regression analysis of antibodies, aPE showed the highest
      association with thrombosis (odds ratio [OR]: 4.2, p < 0.001). Moreover, using a
      multivariate analysis in a case-control subgroup study on 158 patients, IgGaPE
      were found to be significantly associated with venous thrombosis (OR:6;p =
      0.005). Interestingly, 25 of the 40 aPE-positive patients (63%) were negative for
      the APS laboratory criteria. Most of them (21/25) had venous thrombosis,
      recurrent in ten of them. Four patients also suffered from early or late
      miscarriages. Our results underline the strength of the association between the
      presence of aPE and thrombosis and suggest their measurement in thrombotic
      patients, especially when lupus anticoagulant, anticardiolipin or anti-beta(2)
      GPI antibodies are absent.

PMID- 17549298
TI  - Inhibition of thrombin-induced platelet aggregation using human single-chain Fv
      antibodies specific for TREM-like transcript-1.
AB  - TREM-like transcript-1 (TLT-1) is a novel platelet membrane receptor, which has
      been recently characterized in mice. TLT-1 is expressed exclusively in platelets
      and megakaryocytes, and its expression is dramatically upregulated upon platelet
      activation, suggesting that it plays a unique role in hemostasis and/or
      thrombosis. In this study we identified and characterized highly specific human
      monoclonal antibodies that bind to TLT-1 by screening a naive library of single
      chain Fv fragments (scFvs) displayed on filamentous phage (Thomlinson I library).
      These scFvs detected plate-bound TLT-1, captured soluble TLT-1, and readily
      reacted with cell-bound TLT-1 on transfectants and primary human platelets. Most
      importantly, anti-TLT-1 scFvs inhibited thrombin-mediated human platelet
      aggregation. This inhibition was specific for thrombin-induced aggregation and
      was reversible with higher doses of agonist. These data are the first to
      demonstrate a biological role for TLT-1 and its potential as a therapeutic
      target. The human scFvs isolated in this study may represent novel anti-platelet
      therapeutic agents.

PMID- 17549299
TI  - Parnaparin, a low-molecular-weight heparin, prevents P-selectin-dependent
      formation of platelet-leukocyte aggregates in human whole blood.
AB  - Parnaparin, a low-molecular-weight heparin (LMWH), prevents platelet activation
      and interaction with polymorphonuclear leukocyte (PMN) in a washed cell system.
      The in-vitro effect of parnaparin was studied here on platelet-PMN aggregates
      formed with more physiologic approaches in whole blood, in parallel with
      unfractionated heparin and enoxaparin, another LMWH. Citrated blood from healthy
      subjects was stimulated: i) from passage through the "Platelet Function Analyzer"
      (PFA-100), a device that exposes blood to standardized high shear flow through
      collagen/ADP cartridges; ii) by collagen and ADP (2 and 50 mug/ml, respectively)
      added in combination under stirring in an aggregometer cuvette; iii) with
      recombinant Tissue Factor, to generate thrombin concentrations able to activate
      platelets without inducing blood clotting, or iv) the Thrombin Receptor
      Activating Peptide-6 (TRAP-6). Platelet P-selectin and platelet-PMN aggregates
      were measured by flow cytometry upon stimulation of blood. Fibrinogen binding to
      platelets and markers of PMN activation were also detected. Platelet P-selectin
      expression and platelet-PMN aggregate formation were induced in all four
      activation conditions tested. Parnaparin prevented in a concentration-dependent
      manner (0.3-0.8 IUaXa/ml) the expression of P-selectin and the formation of mixed
      aggregates, while the two reference heparin preparations had a much weaker
      effect. Platelet fibrinogen binding and PMN activation markers (fibrinogen
      binding, CD11b and CD40) were also prevented by parnaparin. These data extend in
      more physiological systems of platelet activation, the anti-inflammatory profile
      of parnaparin, previously reported in washed cells. The greater effect of
      parnaparin, as compared to the reference heparins, could be due to chemico
      physical differences possibly unrelated to their anticoagulant effect.

PMID- 17549300
TI  - Hyperresponsiveness of platelets in ischemic stroke.
AB  - Platelet activation and aggregation are critical in the pathogenesis of acute
      ischemic cerebrovascular diseases. The aim of our study was to characterize
      platelet function in patients with acute ischemic stroke or transient ischemic
      attack (TIA), and to evaluate the effect of platelet activation on clinical
      outcome. One hundred thirty-eight consecutive patients with TIA (n = 74) or
      stroke (n = 64) were enrolled in this study. Platelet aggregation in response to
      ADP, epinephrine, arachidonic acid, or collagen, and expression of platelet
      activation receptors (CD62P, CD63, LIBS-1 and PAC-1) in the acute phase and at
      three months follow-up were evaluated. Platelets derived from stroke patients
      were more hyperaggregable in response to agonists in the acute phase compared to
      TIA patients (p[ADP] = 0.002, p[arachidonic acid] = 0.047, p[epinephrine] =
      0.020). Platelet activation was enhanced in the acute phase irrespective of the
      severity of the disease (stroke or TIA) and returned to baseline levels three
      months later. Persistent elevated platelet activation at three months follow-up
      (PAC-1) was associated with increased incidence of recurrent stroke (median,
      [interquartile range] 3.4, [3.0-5.2] versus 2.9, [2.3-4.0], p = 0.048). In
      conclusion, platelets are hyperactive in acute stroke compared with TIA. A more
      intensified dual antiplatelet therapy may be of benefit for stroke patients.

PMID- 17549301
TI  - Biphasic effect of pioglitazone on isolated human endothelial progenitor cells:
      involvement of peroxisome proliferator-activated receptor-gamma and transforming
      growth factor-beta1.
AB  - Endothelial progenitor cells (EPCs) have been implicated in vascular repair and
      found to be functionally impaired in patients with diabetes. We evaluated the
      effects of the anti-diabetic drug pioglitazone on human EPC function and the
      involvement of PPAR-gamma and TGF-beta1. EPCs in culture were characterized at
      day 7 by the development of colony-forming units (CFUs) and flow cytometry
      assessment of differentiation marker (DiI-ac-LDL/lectin, KDR and CD31). Adhesion
      on fibronectin and fibrinogen in flow was analyzed as functional parameter.
      Treatment with pioglitazone for 72 hours increased the number of EPC-CFUs, DiI-ac
      LDL(+)/lectin(+), CD31(+) and KDR(+) EPCs at 1 microM but not at 10 microM. Since
      pioglitazone did not significantly alter proliferation and apoptosis in cultured
      EPCs, the increase in EPC number was most likely attributable to augmented
      adhesion and differentiation. Indeed, pioglitazone increased EPC adhesion in flow
      at 1 microM, an effect prevented by PPAR-gamma and beta2-integrin blockade. In
      contrast, pioglitazone did not promote EPC adhesion at 10 microM; however,
      increased adhesion became evident by co-incubation with a blocking TGF-beta1
      antibody. As determined by ELISA, pioglitazone induced a persistent increase in
      TGF-beta1 secretion only at 10 microM when a significantly elevated expression of
      endoglin, the accessory receptor for TGF-beta1, was also observed. Taken
      together, pioglitazone exerts biphasic effects on the function of isolated EPCs,
      causing a PPAR-gamma-dependent stimulation at 1 microM and a TGF-beta1-mediated
      suppression at 10 microM. These results may help to define optimal therapeutic
      doses of pioglitazone for improving endothelial dysfunction.

PMID- 17549302
TI  - Nuclear factor of activated T cells and early growth response-1 cooperate to
      mediate tissue factor gene induction by vascular endothelial growth factor in
      endothelial cells.
AB  - Based on the finding that tissue factor belongs to a group of genes upregulated
      in endothelial cells by VEGF, but not by EGF, we investigated signals selectively
      triggered by VEGF. Whereas the transcription factor early growth response (EGR)
      1, which has previously been shown by us to be essentially involved in tissue
      factor gene regulation, was similarly induced by both factors, one major
      difference between VEGF and EGF signaling was the activation of the Ca(++)
      mediated calcineurin/nuclear factor of activated T cells (NFAT) pathway by VEGF.
      Consistent with the importance of this pathway for tissue factor induction,
      treatment of endothelial cells with the Ca(++) chelator BAPTA-AM, as well as the
      calcineurin inhibitor cyclosporin A, partially inhibited VEGF-induced tissue
      factor upregulation. Furthermore, tissue factor reporter gene assays revealed a
      synergistic cooperation of NFAT and EGR-1 in the induction of the TF promoter,
      and a physical interaction between the two factors was indicated by co
      immunoprecipitation assays. Another gene upregulated by VEGF predominantly via
      NFAT, which is not induced by EGF, is the DSCR-1 gene. The calcineurin inhibitor
      DSCR-1 seems to be induced by VEGF in a negative feed-back loop to limit NFAT
      activation. When we tested adenoviral overexpression of DSCR-1, VEGF-mediated
      induction of tissue factor mRNA was reduced, and complete suppression could be
      achieved by a combination of viruses expressing DSCR-1 and NAB2, a corepressor of
      EGR-1. These findings support that both, NFAT and EGR-1, are required for tissue
      factor upregulation in response to VEGF.

PMID- 17549303
TI  - Functional promoter polymorphism in the VKORC1 gene is no major genetic
      determinant for coronary heart disease in Northern Germans.
AB  - Recently, the C-allele of polymorphism rs2359612 (VKORC1: c.283+837C>T) in the
      VKORC1 gene has been reported to represent a major risk factor for coronary heart
      disease (CHD), stroke, and aortic dissection in Chinese patients. VKOR activity
      itself is the rate-limiting step in gamma-carboxylation of vitamin K-dependent
      coagulation factors (factors II, VII, IX, X, protein C, S, and Z) and proteins of
      calcium metabolism (matrix Gla protein and osteocalcin). Gamma-carboxylation is
      essential for the biological activity of these proteins that have been previously
      hypothesised to play a role in the pathogenesis of atherosclerosis. It was the
      objective of this study to analyse the VKORC1 genotype frequency in patients with
      CHD and controls from Northern Germany and to investigate the association of
      VKORC1 and CHD risk in patients with an European background. CHD patients (n =
      901) and healthy controls (n = 521) were part of the PopGen biobank. Case and
      control samples were matched for ethnic and geographic origin, age and gender.
      After typing German CHD patients and control individuals, no evidence for a
      statistically significant association was detected between VKORC1 genotype and
      CHD phenotype. Also stratification for gender and myocardial infarction yielded
      no significant results. In conclusion, the discrepant association findings in
      Chinese and German populations may be explained by ethnic differences in genetic
      and perhaps environmental predisposition, modifying the polygenic CHD phenotype
      by interacting with VKORC1 variants and thus conferring disease susceptibility in
      some populations, but not in others.

PMID- 17549304
TI  - Comparative characterization of cellular and molecular anti-restenotic profiles
      of paclitaxel and sirolimus. Implications for local drug delivery.
AB  - Pleiotropic anti-restenotic properties of drugs that are eluted from coated
      stents are critical for efficacy and safety. Little is known about comparative
      drug properties in appropriate human coronary target cell lines for the two
      compounds that are utilized on FDA-approved drug-eluting stent (DES) platforms,
      paclitaxel (PTX) and sirolimus (SRL). Target cell lines that play a pivotal role
      for the pathogenesis of restenosis and vascular healing include human coronary
      artery smooth muscle (CASMC) and endothelial cells (CAEC). PTX and SRL inhibited
      CASMC and CAEC proliferation and migration efficiently. However, there was a
      differential effect on proliferation and migration in CAEC with a more profound
      inhibition of both parameters by PTX, even at low dosages. Induction of
      cytotoxicity and apoptosis was pronounced in PTX- and very modest in SRL-treated
      CASMC and CAEC. PTX increased eNOS activity and nitric oxide (NO) release from
      CAEC. Neutrophilic leukocyte activation and transmigration, which should be
      avoided since it may precipitate adverse coronary events such as restenosis and
      stent thrombosis, was suppressed by SRL, whereas PTX tended to increase
      neutrophilic leucocyte activity. Therefore, although the primary drug target,
      inhibition of mitogen-mediated CASMC proliferation, is effectively accomplished
      by both drugs, auxiliary pharmacological properties that are crucial for the anti
      restenotic drug effect and vascular healing are considerably different between
      PTX and SRL. In comparison with PTX, SRL shows minor interference with
      endothelial cell proliferation and migration, lower levels of cytotoxicity and
      apoptosis, a broader therapeutic range and distinctive immunosuppressive
      properties.

PMID- 17549305
TI  - Murine monoclonal antibodies against murine uPA receptor produced in gene
      deficient mice: inhibitory effects on receptor-mediated uPA activity in vitro and
      in vivo.
AB  - Binding of urokinase plasminogen activator (uPA) to its cellular receptor, uPAR,
      potentiates plasminogen activation and localizes it to the cell surface. Focal
      plasminogen activation is involved in both normal and pathological tissue
      remodeling processes including cancer invasion. The interaction between uPA and
      uPAR therefore represents a potential target for anti-invasive cancer therapy.
      Inhibitors of the human uPA-uPAR interaction have no effect in the murine system.
      To enable in-vivo studies in murine cancer models we have now generated murine
      monoclonal antibodies (mAbs) against murine uPAR (muPAR) by immunizing uPAR
      deficient mice with recombinant muPAR and screened for antibodies, which inhibit
      the muPA-muPAR interaction. Two of the twelve mAbs obtained, mR1 and mR2,
      interfered with the interaction between muPAR and the amino-terminal fragment of
      muPA (mATF) when analyzed by surface plasmon resonance. The epitope for mR1 is
      located on domain I of muPAR, while that of mR2 is on domains (II-III). In cell
      binding experiments using radiolabelled mATF, the maximal inhibition obtained
      with mR1 was 85% while that obtained with mR2 was 50%. The IC(50) value for mR1
      was 0.67 nM compared to 0.14 nM for mATF. In an assay based on modified anthrax
      toxins, requiring cell-bound muPA activity for its cytotoxity, an approximately
      50% rescue of the cells could be obtained by addition of mR1. Importantly, in
      vivo efficacy of mR1 was demonstrated by the ability of mR1 to rescue mice
      treated with a lethal dose of uPA-activatable anthrax toxins.

PMID- 17549306
TI  - Activated coagulation factors in human malignant effusions and their contribution
      to cancer cell metastasis and therapy.
AB  - We have shown that the thrombin G-protein coupled receptors (GPCR) designated as
      protease-activated receptors (PAR-1) are expressed in primary cancer cells
      isolated from peritoneal and pleural malignant effusions. Here, our main goal was
      to evaluate several coagulation and thrombin activation effectors and markers in
      a series of 136 malignant effusions from cancer patients with gastrointestinal,
      lung and mammary carcinomas. All these patients present a highly activated
      coagulation system in blood and their malignant effusions, as indicated by high
      levels of prothrombin F1.2 fragments and D-dimers. Notably, we detected in the
      effusions all the coagulation factors of the tissue factor pathway inducing
      thrombin activation, namely factors VII, V, X and II, as well as high VEGF levels
      and IGF-II in mature and precursor forms. Fibrin clot formation also correlated
      with higher levels of free ionized calcium (iCa), suggesting that iCa and its
      binding protein albumin are regulatory factors for fibrinogenesis in effusions.
      Consequently, thrombin, VEGF and IGFII appear to converge in the promotion of
      survival and invasivity of the metastatic cancer cells from blood to the
      malignant effusions. Thus, we add new insights on the interconnections between
      blood coagulation disorders in cancer patients and thrombin activation in
      malignant effusions, including their functional interaction with PAR in
      metastatic cancer cells. Based on these data we propose to counteract the
      metastatic cascades by targeted invalidation of key effectors of the coagulation
      system. Therefore, potential therapeutic approaches include the application of
      thrombin protease inhibitors, VEGF-blocking antibodies, and drugs targeting the
      VEGF and thrombin signaling pathways, such as tyrosine kinase or GPCR inhibitors.

PMID- 17549307
TI  - Thalidomide and thrombosis. A meta-analysis.
AB  - With the increase in the number of reports and trials on the use of thalidomide
      as a part of the treatment of different medical conditions, particularly multiple
      myeloma (MM), it was observed that this drug might be associated with an increase
      in the risk of venous thromboembolic (VTE) events. It was the objective of this
      study to assess this risk, to check whether it might be affected by the
      concomitant administration of other medications, specifically dexamethasone, and
      to study the effect of anticoagulation and anti-platelet medications. A
      literature search for articles describing the use of thalidomide and the
      resultant VTE events was performed, and 50 articles were reviewed. A sample
      consisting of 3,322 patients resembling the above-mentioned studies was designed,
      and multivariate logistic regression was conducted. While thalidomide,
      dexamethasone and their combination were found to significantly increase the risk
      of VTE events among MM patients by 2.6, 2.8 and eight times, respectively,
      "adequate" anticoagulation significantly reduced the risk. In conclusion,
      patients receiving thalidomide should be carefully monitored for thromboembolic
      events, and those receiving concomitantly dexamethasone or other chemotherapy
      should be followed even more closely. Administering prophylactic doses of low
      molecular-weight heparin or warfarin with therapeutic International Normalized
      Ratio reduces the risk of thromboembolic events among MM patients.

PMID- 17549308
TI  - A new recombinant thrombolytic and antithrombotic agent with higher fibrin
      affinity - a staphylokinase variant. An in-vivo study.
AB  - The recombinant protein SAK-RGD-K2-Hir is characterized by its fibrin-specific
      properties of plasminogen activation combined with antithrombin and antiplatelet
      activities. It was previously shown in our in-vitro studies to be a more potent
      and faster-acting thrombolytic agent compared with standard r-SAK. In order to
      document the effects of the thrombolytic potential of SAK-RGD-K2-Hir we examined
      this protein in an electrically induced carotid artery thrombosis model and
      stasis-induced venous model in rats. In the arterial thrombosis model, a bolus
      injection of SAK-RGD-K2-Hir was less effective than rt-PA and r-SAK. However, the
      most effective in the improvement and maintenance of carotid patency and in
      arterial thrombus mass reduction was SAK-RGD-K2. In contrast, all r-SAK
      derivatives reduced venous thrombus weight significantly in comparison to r-SAK
      and r-Hir. However, the most observable decrease in thrombus weight was obtained
      after application of recombinant proteins containing the r-Hir. The bleeding time
      was significantly prolonged in the animals treated with proteins containing r-Hir
      at a dose of 1.0 mg/kg. There were no observable changes in plasma fibrinogen
      concentration. In conclusion, our findings show thrombolytic activity in
      intravenous bolus injection of the novel thrombolytic agent SAK-RGD-K2-Hir in
      rats. Although this protein compares favourably with r-SAK in rat venous
      thrombolysis, we were unable to confirm the beneficial effects of SAK-RGD-K2-Hir
      over r-SAK and rt-PA in the carotid artery thrombolysis model. Furthermore, our
      results also suggest that SAK-RGD-K2-Hir bears a risk of bleeding, but this may
      be true for higher doses.

PMID- 17549309
TI  - Factitious anticoagulant-resistance as a cause of recurrent arterial bypass graft
      occlusions.

PMID- 17549310
TI  - The growing impact of publications in haemostasis and thrombosis journals.

PMID- 17549311
TI  - Improved visualisation of high-molecular-weight von Willebrand factor multimers.

PMID- 17549312
TI  - Age- and gender-related differences of plasma prothrombin activity levels.

PMID- 17549313
TI  - Gallic acid, a dietary polyphenolic component, blunts the inhibition of platelet
      COX-1 by aspirin: preliminary in-vitro findings.

PMID- 17549314
TI  - Lack of aspirin-induced decrease in thrombin formation in subjects resistant to
      aspirin.

PMID- 17549315
TI  - Platelets and lipoprotein(a) in retinal vein occlusion: mutual targets for
      aspirin therapy.

PMID- 17549317
TI  - Management of multinodular goiter in Germany (Papillon 2005): do the approaches
      of thyroid specialists and primary care practitioners differ?
AB  - AIM: Large-scale survey to focus on management of multinodular goiter and to
      compare the approaches of practitioners in primary care and thyroid specialists
      in Germany. METHODS: Replies to a questionnaire were received from 2,191
      practitioners and 297 thyroid specialists between June 1 and September 30, 2005.
      The hypothetical cases and their modifications described multinodular goiters of
      different sizes with and without toxic nodules. RESULTS: In the workup, TSH
      determination and thyroid sonography were found to be standard procedures.
      Scintigraphy was selected by 80.2% of practitioners and 92.9% of specialists (p <
      0.001), in preference to fine needle aspiration cytology (17.9% of practitioners
      and 34.5% of the specialists, p < 0.001). Only 6.1% of practitioners and 24.4% of
      specialists (p < 0.001) advocated calcitonin screening. Euthyroid multinodular
      goiter (50-80 ml) was treated medically by 67.1% of practitioners and 65.6% of
      specialists, the combination of levothyroxine with iodine being clearly preferred
      (54.5% of practitioners, 52.3% of specialists). For toxic nodular goiter the
      preference for radioiodine therapy was significantly higher (p < 0.001) among
      specialists (67.7%) than among practitioners (47.5%). Referral to surgery was
      recommended for cold nodules with negative cytology by 64.9% of practitioners and
      73.5% of specialists (p = 0.004). CONCLUSIONS: Treatment and diagnostic
      procedures are used to nearly the same extent in primary care and specialist
      institutions, but the opinions diverge over the issues of calcitonin screening
      and referral for radioiodine therapy.

PMID- 17549318
TI  - Administration of additional inactive iodide during radioiodine therapy for
      Graves' disease: who might benefit?
AB  - AIM: Graves' hyperthyroidism and antithyroid drugs empty the intrathyroid stores
      of hormones and iodine. The consequence is rapid 131I turnover and impending
      failure of radioiodine therapy. Can administration of additional inactive iodide
      improve 131I kinetics? PATIENTS, METHODS: Fifteen consecutive patients, in whom
      the 48 h post-therapeutically calculated thyroid dose was between 150 and 249 Gy
      due to an unexpectedly short half-life, received 3 x 200 microg inactive
      potassium-iodide (127I) daily for 3 days (Group A), while 17 consecutive patients
      with a thyroid dose of > or = 250 Gy (Group B) served as the non-iodide group. 48
      hours after 131I administration (M1) and 4 or 5 days later (M2) the following
      parameters were compared: effective 131I half-life, thyroid dose, total T3, total
      T4, 131I-activity in the T3- and T4-RIAs. RESULTS: In Group A, the effective 131I
      half-life M1 before iodine (3.81 +/- 0.93 days) was significantly (p < 0.01)
      shorter than the effective 131I half-life M2 (4.65 +/- 0.79 days). Effective 131I
      half-life M1 correlated with the benefit from inactive 127I (r = -0.79):
      Administration of 127I was beneficial in patients with an effective 131I half
      life M1 of <3 or 4 days. Patients from Group A with high initial specific 131I
      activity of T3 and T4 showed lower specific 131I activity after addition of
      inactive iodine compared with patients from the same group with a lower initial
      specific 131I activity of T3 and T4 and compared with the patient group B who was
      given no additional inactive iodide. This correlation was mathematically
      described and reflected in the flatter gradient in Group A (y = 0.5195x + 0.8727
      for 131I T3 and y = 1.0827x - 0.4444 for 131I T4) and steeper gradient for Group
      B (y = 0.6998x + 0.5417 for 131I T3 and y = 1.3191x - 0.2901 for 131I T4).
      Radioiodine therapy was successful in all 15 patients from Group A. CONCLUSION:
      The administration of 600 microg inactive iodide for three days during
      radioiodine therapy in patients with Graves' hyperthyroidism and an unexpectedly
      short half-life of <3 or 4 days was a safe and effective alternative to the
      administration of a second radioiodine capsule.

PMID- 17549319
TI  - Minimally invasive radio-guided parathyroidectomy on a group of 452 primary
      hyperparathyroid patients: refinement of preoperative imaging and intraoperative
      procedure.
AB  - THE AIM: of this study was to investigate the efficacy of minimally invasive
      radio-guided parathyroidectomy (MIRP) in primary hyperparathyroid (PHPT)
      patients. PATIENTS, METHODS: 452 consecutive PHPT patients were evaluated.
      Inclusion criteria for MIRP were (a) evidence at scintigraphy of a solitary
      parathyroid adenoma (PA); (b) a clear sestamibi uptake in the PA; (c) the absence
      of concomitant thyroid nodules; (d) no history of familial HPT or MEN; (e) no
      history of previous neck irradiation. Intra-operative protocol consisted of the
      injection of a low 37 MBq sestamibi dose in the operating suite 10 min before
      surgery. A hand held 11-mm collimated gamma probe was used. Quick PTH (QPTH) was
      routinely measured. RESULTS: 344 out of the 452 patients met the inclusion
      criteria, and MIRP was successfully performed in 321 of them (93.3%). No major
      intra-operative complication was recorded. MIRP required a mean operative time of
      32 min, and a mean hospital stay of 1.2 d. The parathyroid to background ratio
      (P/B) calculated by the probe was well correlated with the P/B calculated by
      sestamibi SPECT (r = 0.91; p < 0.01), while no significant correlation was found
      between the probe-calculated P/B and the P/B calculated at planar sestamibi scan.
      CONCLUSIONS: In our experience: a) an accurate preoperative localising imaging
      protocol based on planar and SPECT sestamibi scan, and neck US is effective in
      selecting PHPT patients for MIRP, b) the P/B calculated by sestamibi SPECT seems
      able to predict the probe-calculated P/B more accurately than the P/B calculated
      at planar scan, c) the low 37 MBq sestamibi dose protocol proved to be a safe and
      effective approach to perform MIRP.

PMID- 17549320
TI  - Cerebral haemodynamics during hypo- and hypercapnia: determination with
      simultaneous 15O-butanol-PET and transcranial Doppler sonography.
AB  - AIM: Transcranial Doppler sonography (TCD) is increasingly used in
      cerebrovascular disease for monitoring brain perfusion. It allows estimation of
      cerebral blood flow (CBF) by the measurement of cerebral blood flow velocity
      (CBFV). The CBFV as well as CBF are intimately associated with the intravascular
      CO2-concentration. Thus, hyper- or hypocapnia can be used to induce a defined
      range of blood flows. The aim of our study was the comparison of vasomotor
      reactivity assessed with simultaneous TCD and quantitative regional CBF
      measurements (rCBF) by PET (serving as the reference method for in-vivo
      quantification of rCBF). PATIENTS, METHODS: Six healthy young volunteers
      participated in this study. CBF was measured using 15O-butanol PET. A flow and
      dispersion-model was fitted to the measured time activity curves using arterial
      input curves. Each subject underwent five scans at five different end-tidal CO2
      levels (EtCO2): 25, 32, 40, 48, and 55 mmHg. CBFV was assessed by continuous
      bilateral TCD of the middle cerebral artery (MCA). Volumes of interest for rCBF
      determination were placed in grey matter of the prefrontal cortex (PFC) as
      determined from individual MRIs. Comparisons between the rCBF, EtCO2 and CBFV
      were carried out with regression and correlation analysis and paired t-tests.
      RESULTS: Strong positive linear correlations of rCBF and CBFV with the CO2
      concentration and linear relationships between rCBF and CBFV were found in each
      individual. Normalised CO2-reactivities measured by TCD and PET were closely
      correlated. CONCLUSIONS: TCD-measurements of vascular reactivity in healthy
      volunteers show a high correlation to those acquired with PET that serves as the
      reference method of quantitative rCBF-measurement. The results of the MCA
      insonation are a close approximation of the rCBF changes induced by variations of
      EtCO2.

PMID- 17549321
TI  - Effect of scatter and attenuation correction in ROI analysis of brain perfusion
      scintigraphy: phantom experiment and clinical study in patients with unilateral
      cerebrovascular disease.
AB  - The AIM of this study was to evaluate the effect of scatter and attenuation
      correction in region of interest (ROI) analysis of brain perfusion single-photon
      emission tomography (SPECT), and to assess the influence of selecting the
      reference area on the calculation of lesion-to-reference count ratios. PATIENTS,
      METHODS: Data were collected from a brain phantom and ten patients with
      unilateral internal carotid artery stenosis. A simultaneous emission and
      transmission scan was performed after injecting 123I-iodoamphetamine. We
      reconstructed three SPECT images from common projection data: with scatter
      correction and nonuniform attenuation correction, with scatter correction and
      uniform attenuation correction, and with uniform attenuation correction applied
      to data without scatter correction. Regional count ratios were calculated by
      using four different reference areas (contralateral intact side, ipsilateral
      cerebellum, whole brain and hemisphere). RESULTS: Scatter correction improved the
      accuracy of measuring the count ratios in the phantom experiment. It also yielded
      marked difference in the count ratio in the clinical study when using the
      cerebellum, whole brain or hemisphere as the reference. Difference between
      nonuniform and uniform attenuation correction was not significant in the phantom
      and clinical studies except when the cerebellar reference was used. Calculation
      of the lesion-to-normal count ratios referring the same site in the contralateral
      hemisphere was not dependent on the use of scatter correction or transmission
      scan-based attenuation correction. CONCLUSION: Scatter correction was
      indispensable for accurate measurement in most of the ROI analyses. Nonuniform
      attenuation correction is not necessary when using the reference area other than
      the cerebellum.

PMID- 17549322
TI  - Equipment-independent reference values for dopamine transporter imaging with 123I
      FP-CIT.
AB  - AIM: Reliable reference values are helpful to interpret and compare the results
      of dopamine transporter imaging with SPECT. Since semi-quantitative reference
      values cannot be easily transferred between imaging equipments, this study aimed
      to establish equipment independent normal values for the true striatal binding of
      123I-FP-CIT. PATIENTS, METHODS: Specific striatal FP-CIT binding of 6 healthy
      volunteers and 26 patients with essential tremor were used to generate a
      reference range by applying an equipment specific resolution dependent factor to
      compensate for recovery effects. This factor has been determined previously by a
      series of standardized phantom measurements of an anthropomorphic basal ganglia
      phantom. Herewith, the resulting DAT binding values represent the expected true
      specific binding in the striatum. RESULTS: On average, true specific striatal
      binding was 5.83 +/- 0.96 in healthy controls, 5.25 +/- 0.67 in patients with
      essential tremor and 5.36 +/- 0.75 in the entire study cohort. CONCLUSION: These
      preliminary results may serve as a basis for the generation of a generally
      accepted equipment independent reference range for dopamine transporter imaging
      with 123I-FP-CIT. By a simple phantom measurement that can be accomplished within
      one day factors related to specific imaging equipment and processing can be
      corrected for, resulting in specific binding values which may enable a more
      standardized interpretation of dopamine transporter scans.

PMID- 17549323
TI  - Enriched environment and astrocytes in central nervous system regeneration.
AB  - Rehabilitation medicine is entering a new era, based on the knowledge that the
      central nervous system has a substantial capacity for repair and regeneration.
      This capacity is used in 3 distinct but overlapping situations: (i) routine
      housekeeping throughout life (i.e. taking care of normal wear-and-tear); (ii)
      older age, when functional reserves of various kinds are depleted, resulting in
      cognitive, motor, and other deficits; and (iii) contexts in which a neurological
      deficit reflects an acute or chronic pathological process, such as neurotrauma,
      stroke, or neurodegenerative disease. The positive message here is two-fold.
      First, some aspects of regeneration occur even in the adult and ageing brain and
      spinal cord, and we are starting to unravel the underlying molecular mechanisms.
      Secondly, novel therapeutic approaches and targets are emerging that will
      substantially increase the efficiency and efficacy of rehabilitation and will
      transform rehabilitation into a discipline focusing both on its traditional
      domain and on prevention, ultimately across all the age categories. This review
      attempts to sum up the present knowledge about an enriched environment, currently
      the single most efficient plasticity- and regeneration-promoting paradigm. It
      also summarizes research showing that astrocytes - considered only years ago
      merely to nurse and support neurones - are a novel and highly interesting target
      for regenerative strategies in the brain and spinal cord.

PMID- 17549324
TI  - ICF core sets for low back pain: do they include what matters to patients?
AB  - OBJECTIVE: To investigate whether the International Classification of Functioning
      Disability and Health (ICF) Core Sets for low back pain encompass the key
      functional problems of patients. DESIGN: Cross-sectional evaluation of patient
      centred problems with low back pain. SUBJECTS: A total of 402 patients living in
      the UK recruited into a randomized clinical trial. METHODS: Patients with acute
      or subacute low back pain were asked to identify: (i) the one thing they find
      most difficult to do, and (ii) something they usually enjoyed but were unable to
      do because of their back pain. Two raters classified responses according to the
      ICF. Inter-rater agreement was measured using the kappa statistic. The response
      categories were examined for inclusion within the Core Sets. RESULTS: For
      question (i) above, agreement between raters was 323/397 (81%), kappa (95%
      confidence interval (95% CI)) = 0.78 (0.73-0.82). A total of 329 (83%) fell
      within the ICF Brief Core Set; all except 3 were contained within the
      Comprehensive Core Set. For question (ii) agreement was 290/312 (93%), kappa (95%
      CI) = 0.91 (0.87-0.95). Only 54 (17%) of these fell within the Brief Core Set;
      the 2 most chosen categories (recreation and leisure: d920; caring for household
      objects: d650) accounted for 70% of responses, and were not included. All except
      2 responses were encompassed by the Comprehensive Core Set. CONCLUSION: Addition
      of codes d920 and d650 to the low back pain Brief Core Set would significantly
      increase the inclusion rate in this cohort.

PMID- 17549325
TI  - A comparison of four disability scales for Turkish patients with neck pain.
AB  - OBJECTIVE: The Neck Disability Index, the Northwick Park Pain Questionnaire, the
      Copenhagen Neck Functional Disability Scale and the Neck Pain and Disability
      Scale are widely used scales for assessing neck pain or disability. The aim of
      this study was to determine the most suitable scale for Turkish patients with
      neck pain. METHODS: All scales were translated into Turkish, administered to 102
      patients with neck pain, then compared with regard to their construct validity,
      reliability, responsiveness, acceptability and usefulness. RESULTS: The scales
      were similar in their high validity, reliability standards and sensitivity to
      change, but differed in their acceptability and usefulness. The item about
      driving in the Neck Disability Index and the Northwick Park Pain Questionnaire
      was omitted by 69.6% of patients for reasons other than a neck problem.
      CONCLUSION: All scales were reliable, valid and sensitive instruments, with
      similar psychometric properties. The scale that most adequately reflects the
      patient should be chosen.

PMID- 17549326
TI  - Do cervical degenerative changes in women with chronic neck pain affect function?
AB  - OBJECTIVE: Previous investigations suggest little association between clinical
      findings and radiographic degenerative findings. However, the association between
      degenerative changes and neck function has not been investigated. DESIGN: A cross
      sectional study. SUBJECTS: Data were collected from 179 female office workers
      aged 25-53 years with chronic neck pain who were referred for institutional
      rehabilitation. METHODS: Radiographs of the cervical spine, and neck function
      including isometric muscle strength and passive range of motion were evaluated.
      All subjects completed self-report questionnaires including questions about neck
      pain and disability. RESULTS: Fifty-nine percent of the women presented
      degenerative changes and they were older than women without the changes
      (p=0.001). Neck pain and disability were comparable when the patients were put
      into subgroups according to the radiological cervical changes. Neck mobility and
      muscle strength were comparable in women with or without degenerative changes,
      except for a lower rotational range of motion in women with degenerative changes
      (p=0.009). CONCLUSION: The results suggest that the degenerative changes in
      cervical plain films are poorly related to the severity of symptoms or neck
      function in women with chronic neck pain working in sedentary occupations.

PMID- 17549327
TI  - Evaluation of cognitive behavioural training and physical activity for patients
      with stress-related illnesses: a randomized controlled study.
AB  - OBJECTIVE: To evaluate the effects of a cognitive behavioural training programme
      and a physical activity programme for patients with stress-related illnesses.
      DESIGN: In a randomized controlled study, patients were allocated randomly to 1
      of 3 groups, where group 1 participated in a cognitive behavioural training
      programme, group 2 participated in a physical activity programme, and group 3,
      the control group, was offered usual care for the course of the study. SUBJECTS:
      A total of 75 patients participated in the study. They had been on sick leave for
      at least 50% of the time for between 1 month and 2 years due to stress-related
      illnesses. METHODS: Measurements of autonomic activity, pressure-pain thresholds
      and subjective ratings of health and behaviour were made before and after a 10
      week intervention period, and at 6 and 12 months after the intervention. RESULTS:
      Minor differences in autonomic activity and pressure-pain thresholds were found
      between the groups immediately after the intervention. At the 6- and 12-month
      follow-up assessments, the differences were no longer present. Patients in the
      cognitive behavioural training group improved their ratings of general health
      compared with the physical activity group throughout the study. CONCLUSION: The
      study showed little difference in the effect of cognitive behavioural training
      and physical activity, compared with usual care, for patients with stress-related
      illnesses.

PMID- 17549328
TI  - Intramuscular and nerve root stimulation vs lidocaine injection to trigger points
      in myofascial pain syndrome.
AB  - OBJECTIVES: To compare the efficacies of an intramuscular stimulation technique
      and 0.5% lidocaine injection to trigger points in myofascial pain syndrome.
      PARTICIPANTS: Forty-three people with myofascial pain syndrome of the upper
      trapezius muscle. INTERVENTIONS: Twenty-two subjects were treated with
      intramuscular stimulation and another 21 with 0.5% lidocaine injection at all the
      trigger points on days 0, 7 and 14. RESULTS: Intramuscular stimulation resulted
      in a significant reduction in Wong-Baker FACES pain scale scores at all visits
      and was more effective than trigger point injection. Intramuscular stimulation
      also resulted in significant improvement on the Geriatric Depression Scale -
      Short Form. Local twitch responses occurred in 97.7% (42/43) of patients. All the
      passive cervical ranges of motion were significantly increased. Post-treatment
      soreness was noted in 54.6% of patients in the intramuscular stimulation group
      and 38.1% in the trigger point injection group, respectively, and gross
      subcutaneous haemorrhage (> 4 cm2) was seen in only one patient in the trigger
      point injection group. CONCLUSION: In managing myofascial pain syndrome, after
      one month intramuscular stimulation resulted in more significant improvements in
      pain intensity, cervical range of motion and depression scales than did 0.5%
      lidocaine injection of trigger points. Intramuscular stimulation is therefore
      recommended for myofascial pain syndrome.

PMID- 17549329
TI  - Evaluation of arm and prosthetic functioning in children with a congenital
      transverse reduction deficiency of the upper limb.
AB  - OBJECTIVE: To assess upper extremity functioning of children with unilateral
      transverse upper limb reduction deficiency, using standardized instruments, and
      to investigate their validity and reliability. DESIGN: Cross-sectional study.
      SUBJECTS: Twenty subjects aged 4-12 years; 9 prosthetic users and 11 non-users.
      METHODS: The Assisting Hand Assessment, Unilateral Below Elbow Test, Prosthetic
      Upper extremity Functional Index and ABILHAND-Kids were assessed in all children.
      Users were tested with and without their prosthesis. We compared results of users
      and non-users, and of users with and without their prosthesis. Validity was
      determined by testing hypotheses and correlations with other measures. Test
      retest reliability was assessed from repeated measurements in 10 children.
      RESULTS: Children with an upper limb reduction deficiency performed well on daily
      activities. They could use their prosthesis in 68% of the activities, but were
      currently using it in only 30%. Children find their prosthesis useful for
      specific activities, rather than for daily activities in general. The Assisting
      Hand Assessment and Prosthetic Upper extremity Functional Index showed best
      validity; test-retest reliability was good to excellent. CONCLUSION: The use of
      standardized instruments adds relevant information on functioning of children
      with an upper limb reduction deficiency. We found additional support for validity
      and reliability of, in particular, the Assisting Hand Assessment and Prosthetic
      Upper extremity Functional Index.

PMID- 17549330
TI  - Clinical and prognostic properties of standardized and functional aphasia
      assessments.
AB  - OBJECTIVE: To compare standardized and functional aphasia tests in patients after
      acute stroke. DESIGN: Data were collected at baseline and at 6 months in 2
      prospective single-centre studies: one observational study (study I, n=119) and
      one randomized trial of moclobemide vs placebo (study II, n=89). SUBJECTS:
      Patients with aphasia after acute stroke. METHODS: Degree of aphasia was examined
      using the Coefficient (Coeff) in Norsk Grunntest for Afasi (standardized) and the
      Amsterdam-Nijmegen Everyday Language Test (ANELT) (functional). Statistical
      comparisons were made using one-way analysis of variance and multivariate
      regression analyses. RESULTS: The degree of aphasia measured with Coeff and ANELT
      correlated closely throughout the study (r2=0.71-0.87, p<0.0001). In study I, 24
      patients recovered completely within 6 months. A Coeff >or= 49 and ANELT >or= 3.5
      predicted complete recovery equally well. Coeff was sensitive to differentiate
      between patients with low values on ANELT, whereas ANELT was sensitive to
      differentiate between patients with high Coeff values. CONCLUSION: The 2 tests
      show a close and consistent correlation over time and are equally sensitive to
      improvement. They have a similar capacity to predict complete recovery. A
      standardized test appears to be more suitable for patients with aphasia in the
      acute stage, while a functional test is more suitable in the subacute/chronic
      stage.

PMID- 17549331
TI  - Complications following spinal cord injury: occurrence and risk factors in a
      longitudinal study during and after inpatient rehabilitation.
AB  - OBJECTIVE: To assess the occurrence and risk factors for complications following
      spinal cord injury during and after inpatient rehabilitation. DESIGN: Multicentre
      longitudinal study. SUBJECTS: A total of 212 persons with a spinal cord injury
      admitted to specialized rehabilitation centres. METHODS: Assessments at the start
      of active rehabilitation (n=212), 3 months later (n=143), at discharge (n=191)
      and 1 year after discharge (n=143). RESULTS: Multi-level random coefficient
      analyses revealed that complications were common following spinal cord injury.
      Most subjects reported neurogenic and musculoskeletal pain, or had spasticity at
      each assessment. During the year after discharge, complications remained common:
      urinary tract infections and pressure sores affected 49% and 36% of the
      population, respectively. The degree of pain decreased, whereas the degree of
      spasticity increased significantly during inpatient rehabilitation. Overall,
      increased age, increased body mass index, traumatic lesion, tetraplegia, and
      complete lesion all increased the risk of complications. CONCLUSION:
      Complications are common following spinal cord injury. They need specific
      attention after discharge from inpatient rehabilitation and within
      subpopulations.

PMID- 17549332
TI  - Home trials of a speech synthesizer in severe dysarthria: patterns of use,
      satisfaction and utility of word prediction.
AB  - OBJECTIVE: The aim of this study was to evaluate a speech synthesizer with
      respect to patterns of use and satisfaction, during a 2-month trial at home, and
      the usefulness of the word prediction function. DESIGN: Prospective study.
      PARTICIPANTS: Of the 24 patients with severe dysarthria recruited, 10 completed
      the study. Five patients had cerebral palsy, 3 amyotrophic lateral sclerosis, one
      locked-in syndrome, and one anoxic brain damage. Mean age was 32 (standard
      deviation 21) years (range 9-66 years). METHODS: Each participant received 10
      hours of training with the device (Dialo) and then used it at home for 2 months.
      The main outcome measures were: level of use recorded by the device, Quebec User
      Evaluation of Satisfaction with Assistive Technology (QUEST) satisfaction score
      (maximum = 5), and time needed to take dictations of standard-dictionary and
      personal-dictionary words with and without word prediction. RESULTS: Level of use
      varied widely across participants. Overall satisfaction at the end of the home
      trial was high, with a mean QUEST score of 3.4 (SD 1) and was related to the
      level of use of the device. Level of satisfaction at the end of the training
      session could not predict the level of use at home. No significant differences
      were found in dictation-taking times with and without word prediction. However, 6
      of the 10 patients took dictation faster with than without word prediction.
      CONCLUSION: This study provides the first evidence supporting the benefits of a
      speech synthesizer used at home for several weeks. Word prediction is useful for
      some patients even if increase in dictation speed did not reach significance.

PMID- 17549333
TI  - One-year follow-up of mild traumatic brain injury: cognition, disability and life
      satisfaction of patients seeking consultation.
AB  - OBJECTIVE: To investigate cognitive function, symptoms, disabilities and life
      satisfaction of patients with mild traumatic brain injury who accepted
      consultation one year post-trauma. DESIGN: Prospective study. PATIENTS: Sixty
      nine patients (16 accepted the consultation offered, 53 declined). METHODS: At
      follow-up, the patients answered questionnaires about symptoms, disabilities
      (RHFUQ) and life satisfaction (LiSat-11). The patients who underwent consultation
      and their healthy control subjects were administered a neuropsychological
      evaluation. RESULTS: In the group undergoing consultation, the number of
      cognitive tests with outcomes below cut-off limits (-1.5 SD) was statistically
      significantly higher compared with a control group (21 tests in 11 patients vs 8
      tests in 7 control subjects; p=0.025). The number of patients with one or more
      disability was statistically significantly higher among patients with
      consultation than without (94% and 34%, respectively; p<0.001). Total RHFUQ score
      was statistically significantly higher for the group with consultation than
      without (5.9 +/- 3.7 and 1.1 +/- 2.3, respectively, p<0.001). The group with
      consultation exhibited a lower level of life satisfaction (41.5 +/- 10.4 vs 45.8
      +/- 13.8 for the non-consulting group; p=0.057). CONCLUSION: The high frequency
      of occurrence of disabilities and lower cognitive functioning, together with the
      lower level of life satisfaction, appear to characterize patients choosing
      consultation 1 year post-injury. This highlights the importance of offering
      consultation for persons suffering mild head injuries.

PMID- 17549334
TI  - Impact of depressive mood on lifestyle changes in patients with coronary artery
      disease.
AB  - OBJECTIVE: The aims of this study were to investigate the time-course of
      depressive mood in patients with coronary artery disease during a secondary
      prevention rehabilitation program, and to analyse how different pre-treatment
      levels of depressive mood during a treatment phase were related to the degree of
      lifestyle change at 36 months follow-up. SUBJECTS: The study group comprised 109
      of the original 183 consecutive coronary artery disease patients (91 male and 18
      female) of whom 48 recently had experienced an acute myocardial infarction, 36
      had been treated with coronary bypass surgery, 13 with percutaneous transluminal
      coronary angioplasty, and 12 had angina pectoris that had not been invasively
      treated. The subjects were divided into 3 subgroups based on their pre-treatment
      level of depressive mood. METHODS: Depressive mood was assessed at baseline,
      after 4 weeks and 12 months, using the depression subscale of the Hospital
      Anxiety and Depression scale. Lifestyle changes analysed included diet, smoking,
      relaxation (stress management) and exercise. RESULTS: Overall depressive mood
      ratings were significantly lower, both at the 4-week and 12-month assessments,
      compared with baseline, with the greatest improvements in patients with higher
      Hospital Anxiety and Depression measured depression. Original levels of
      depressive mood were not found to influence change of lifestyle habits during a
      36-month follow-up period. CONCLUSION: Depressive mood might not be an obstacle
      to lifestyle changes when participating in a behaviourally oriented
      rehabilitation program including exercise-training, which might be a component
      important for improved depressive mood.

PMID- 17549335
TI  - Tensor magnetic resonance imaging in a case of mild traumatic brain injury with
      lowered verbal intelligence quotient.
AB  - We report the case of a 31-year-old man who had mild traumatic brain injury as a
      result of an accident at the age of 24 years. Seven years after the trauma, at
      the age of 31 years, he had a lower verbal intelligence quotient than performance
      intelligence quotient by the Wechsler Adult Intelligence Scale - Revised, and
      frontal lobe dysfunction, for example, difficulty in maintaining or changing the
      set as revealed by the Wisconsin Card Sorting Test Keio Version. Conventional
      brain magnetic resonance imaging had not shown any abnormalities. Abnormal brain
      areas were detected on magnetic resonance diffusion tensor imaging. On
      tractography, some fibres from the corpus callosum towards the frontal cortex
      were noted to be lacking in the left hemisphere compared with the right. The
      tractography results may explain the patient's lowered verbal intelligence
      quotient and focal left frontal lobe dysfunction. Diffusion tensor imaging is
      therefore helpful in detecting lesions in mild traumatic brain injury with
      diffuse axonal injury.

PMID- 17549336
TI  - Does fascicular neurotomy have long-lasting effects?

PMID- 17549338
TI  - Potential for molecular-targeted therapy targeting human epidermal growth factor
      receptor-2 for invasive bladder cancer.
AB  - Expression of human epidermal growth factor receptor-2 (HER-2/neu or HER-2)
      oncoprotein in invasive bladder cancer was examined by immunohistochemical
      staining in order to evaluate the potential for molecular-targeted therapy
      targeting HER-2 as a tailor-made treatment for patients with invasive bladder
      cancer. This study included 40 patients who were examined at Aichi Medical
      University Hospital and were pathologically diagnosed with invasive transitional
      cell carcinoma of the bladder (pT2 to pT4). Immunohistochemical staining using a
      Hercep test kit was performed to detect HER-2 expression, which was classified
      into four levels from 0 to 3+ by two experienced pathologists, with 2+ and 3+
      determined as positive. HER-2 staining in the primary tumor was determined as 0
      in 9 (22.5%) patients, 1+ in 14 (35%), 2+ in 10 (25%), and 3+ in 7 (17.5%),
      resulting in 17 (17/40, 42.5%) HER-2-positive patients. According to the
      classification of grade, one (1/3, 33.3%) grade 2 patient and 16 (16/37, 43.2%)
      grade 3 patients were HER-2 positive (p=0.99). According to the classification of
      stage, 12 (12/22, 54.5%) pT2 patients, 2 (2/13, 15.3%) pT3 patients, and 3 (3/5,
      60%) pT4 patients were HER-2 positive (p=0.05). Lymph node metastasis was found
      in 10 patients, and 3 (3/6, 50%) pN2 patients were HER-2 positive (p=0.32). There
      was a statistically significant difference between patients with HER-2-positive
      primary tumors and those with HER-2-positive metastatic lymph nodes (p=0.02).
      This study suggested that 42.5% of patients with invasive bladder cancer may
      benefit from molecular-targeted therapy targeting HER-2, and that the efficacy of
      molecular-targeted therapy can be expected even for patients with lymph node
      metastases as long as their primary tumors are HER-2 positive.

PMID- 17549339
TI  - Epithelioid gastric stromal tumours of the antrum in young females with the
      Carney triad: a report of three new cases with mutational analysis and
      comparative genomic hybridization.
AB  - Carney triad is a rare non-hereditary condition affecting young females and
      characterized by metachronous or synchronous occurrence of epithelioid
      gastrointestinal stromal tumours (GISTs), pulmonary chondroma and extra-adrenal
      paraganglioma. The genetic alterations in Carney triad-related GISTs have not
      been well studied. We evaluated GISTs from three females with incomplete Carney
      triad for KIT and PDGFRA mutations and studied the DNA by comparative genomic
      hybridization (CGH). All GISTs originated in the antrum and had a monotonous
      epithelioid morphology. Two patients had GISTs and pulmonary chondroma and one
      had GISTs and paraganglioma. Initial manifestation was GIST (n=1), pulmonary
      chondroma (n=1) and bladder paraganglioma (n=1). Time to the second component was
      2-13 years. Two patients were alive at 108 and 168 months (one with metastases)
      and one died of the disease 3 years later. All cases were wild-type for KIT exons
      9, 11, 13, 17 and PDGFRA exons 12 and 18. CGH revealed 14 aberrations (mean,
      4.7/tumour) including 11 gains (X, 1q, 5p, 8q, 9p, 12p, 13q, 18p, 19q), 2
      amplifications (1q, 19p) and one loss (13q). Carney triad-related GISTs do not
      only lack conventional KIT and PDGFRA mutations, but they also lack the non
      random loss of 14q and 22q characteristic of their sporadic counterparts,
      suggesting an origin through a distinct pathogenetic pathway.

PMID- 17549340
TI  - Detection of activated K-ras in non-small cell lung cancer by membrane array: a
      comparison with direct sequencing.
AB  - The ability to detect K-ras oncogene may provide additional information for the
      management of patients with non-small cell lung cancer (NSCLC). In the present
      study, we detected the K-ras oncogene in 76 patients with NSCLC by two methods:
      direct sequencing of K-ras in tumor tissues and membrane array detection of the
      gene overexpression specific for activated K-ras in peripheral blood. The results
      showed that 28 (36.8%) of the 76 Taiwanese NSCLC patients had K-ras mutations,
      with a frequency of 36.4% (20/55) in adenocarcinomas and 38.1% (8/21) in squamous
      cell carcinomas. The K-ras mutations were more frequently found in smokers than
      in non-smokers (51.4 vs. 24.4%, P=0.015). The incidences of K-ras mutation in the
      subgroups of non-smokers and squamous cell carcinomas are relatively higher in
      Taiwan than in other countries. On the other hand, the membrane array method
      could positively detect circulating activated K-ras in all of the 27 NSCLC
      patients with K-ras mutations at codons 12, 13 and 61, and in 4 of the 48
      patients with wild-type K-ras. Our results suggest that the K-ras oncogene
      membrane array serves as a sensitive and convenient tool for the detection of K
      ras oncogene, and therefore, has a great potential for clinical applications.

PMID- 17549341
TI  - Analysis of the expression of estrogen receptor, progesterone receptor and
      chicken ovalbumin upstream promoter-transcription factor I in ovarian epithelial
      cancers and normal ovaries.
AB  - Sex hormones are involved in the carcinogenesis of some gynecologic cancers, and
      the status of their receptors represents an indicator of prognosis and of the
      therapeutic response in breast and endometrial cancers. In the ovary, this role
      is not clearly defined, with epithelial cancers being poorly responsive to
      hormone therapy. COUP-TFI (chicken ovalbumin upstream promoter-transcription
      factor I) is an orphan nuclear receptor, which is expressed in various tissues
      and regulates the estrogen receptor (ER) by competition for DNA binding. To
      investigate the role of these receptors in ovarian carcinogenesis and their
      implications for cancer prognosis, we evaluated the immunohistochemical
      expression of ER, progesterone receptor (PR) and COUP-TFI in benign and malignant
      ovarian epithelial neoplasms and in normal ovaries. A total of 113 ovarian
      specimens, including 40 diagnosed as malignant epithelial neoplasms (group A), 45
      as benign epithelial tumors (group B), and 28 from normal ovaries (group C) were
      analyzed. Immunoexpression of ER was observed in 70% of patients of group A,
      57.8% of group B and 57.1% of group C, with no significant difference between
      groups (p=0.426). Immunoexpression of PR was significantly lower in group A
      (12.5%) compared to group B (42.2%) and group C (32.1%) (p=0.010). Similarly,
      COUP-TFI was expressed in only 10% of group A patients, a rate significantly
      lower than that observed for group B (31.1%) and group C (39.3%) (p=0.014). No
      association was observed between the expression of these markers and increased
      survival or clinical prognostic variables. Multivariate analysis revealed a
      residual tumor <1 cm as the most significant clinical prognostic factor in group
      A (p=0.010, OR=4.14). These data support the importance of cytoreduction in the
      treatment of ovarian cancer, the role of steroid receptors in the mechanism of
      carcinogenesis, and the need for selection of subgroups that may respond to
      hormone therapy.

PMID- 17549342
TI  - Sensitivity to CPT-11 and platinum derivatives of stage I/II node-negative
      breast, lung, and gastric cancer with occult neoplastic cells in lymph node
      sinuses.
AB  - Tumor sensitivity to anticancer drugs such as CPT-11 and platinum derivatives was
      investigated by assessing Topo-1 and Bax/ERCC-1 expression in patients with stage
      I/II breast, lung, and gastric cancer who were positive for ONCs, and tumor
      sensitivity was compared between CPT-11 and platinum derivatives. In the
      recurrence group (RG) (n=5), immunohistochemistry revealed high expression of
      Topo-1 in 3 patients (60%) and low expression in 2 patients (40%), while the non
      recurrence group (N-RG) (n=17) showed high Topo-1 expression in 3 patients
      (17.6%) and low expression in 14 patients (82.4%) (not significant; N.S.). High
      Bax expression combined with low ERCC-1 expression was observed in 2 patients
      (40%) from the RG and other patterns of expression were seen in 3 patients (60%),
      while high Bax/low ERCC-1 expression was observed in 3 patients (17.6%) from the
      N-RG and other patterns were found in 14 patients (82.4%) (N.S.). PCR analysis of
      Topo-1 expression in the RG (n=4) revealed high expression in 4 patients (100%),
      while the N-RG (n=5) showed high expression in 3 patients (60%) and low
      expression in 2 patients (40%) (N.S.). With respect to ERCC-1, PCR analysis of
      the RG (n=4) also revealed high expression in 4 patients (100%), while the N-RG
      (n=5) again showed high expression in 3 patients (60%) and low expression in 2
      patients (40%) (N.S.). There were significant differences between the expression
      of high Topo-1 and low ERCC-1 in the RG (p<0.01). These results suggest that
      tumor sensitivity to CPT-11 may be higher than that for platinum derivatives in
      patients with node-negative stage I/II breast, lung, or gastric cancer who are
      positive for ONCs.

PMID- 17549343
TI  - Expression of Epstein-Barr virus in renal cell carcinoma.
AB  - There have been few studies regarding the etiology of renal cell carcinoma. To
      examine the possible involvement of Epstein-Barr virus (EBV) in this disease, 9
      renal cell carcinoma (RCC), 2 nephroblastoma (Wilms' tumor) and 2 RCC cell lines
      were subjected to mRNA in situ hybridization and indirect immunofluorescence
      staining. Messenger RNA in situ hybridization using BamHIW, EBNA LP, EBNA 2 and
      EBER1 probes of EBV revealed signals in all the examined samples, although some
      samples showed weak signals using the EBNA LP probe. Indirect immunofluorescence
      staining using anti-EBNA LP, anti-EBNA2, anti-LMP1 and anti-BZLF1 antibodies
      showed definitive fluorescence. PCR also revealed EBV DNA in all 8 RCC specimens
      including 7 cases other than hybridization and fluorescence. EBV infected all the
      RCC and nephroblastoma irrespective of the histological or clinical stage. On the
      other hand, EBV expression was stronger in papillary and clear cell-type RCC than
      chromophobe cell-type, as well as being stronger in the higher grades of RCC.
      These results suggest that the expression of EBV may be involved in the
      pathogenesis of RCC and nephroblastoma.

PMID- 17549344
TI  - Anti-tumor effects of bevacizumab in combination with paclitaxel on head and neck
      squamous cell carcinoma.
AB  - Human tumors are dependent on angiogenesis for growth, and the vascular
      endothelial growth factor (VEGF) is a major regulator of this process.
      Bevacizumab (Avastin), a monoclonal antibody directed against VEGF, has shown
      promise in treating a variety of cancers. In this study, we first examined the
      anti-tumor effects of bevacizumab on head and neck squamous cell carcinoma
      (HNSCC). Then we examined the effects of bevacizumab combined with paclitaxel, a
      chemotherapeutic agent, in HNSCC. This is the first demonstration of the anti
      tumor effects of bevacizumab on HNSCC. In vitro, bevacizumab did not show any
      antiproliferative effects against the HNSCC cell lines. However, in vivo,
      bevacizumab showed dramatic anti-tumor effects against HNSCC tumor xenografts in
      mice. In addition, treatment with a bevacizumab-paclitaxel combination resulted
      in a remarkable inhibition of the HNSCC tumor xenografts, compared to the effects
      of each agent separately. A decreased blood vessel density and an increased
      apoptotic index were seen in the shrunken tumors. These results suggest that
      bevacizumab in combination with paclitaxel could have useful clinical application
      in HNSCC.

PMID- 17549345
TI  - CYP2A6 overexpression in human lung cancers correlates with a high malignant
      status.
AB  - CYP2A6 is a major phase I enzyme metabolizing tobacco-specific nitrosamines,
      implicated as risk factors for lung cancer. In this study, immunohistochemistry
      and in situ hybridization (ISH) for CYP2A6 with human lung cancer tissues (n=31)
      obtained by surgical resection showed significantly higher immunoreactivity in
      the cases with lymph node metastasis. The adenocarcinoma cases (n=23) with lymph
      node metastasis or large tumor size showed a high immunoreactivity for CYP2A6.
      The squamous cell carcinoma cases (n=6) with large tumor size showed a tendency
      for low CYP2A6 immunoreactivity. ISH for CYP2A6 revealed mRNA expression in both
      adenocarcinoma and squamous cell carcinoma cells. The data suggest that CYP2A6
      could have an important role in the development and proliferation of lung
      carcinomas. With adenocarcinomas, CYP2A6 could be a target candidate for
      therapeutic and chemopreventive intervention.

PMID- 17549346
TI  - Expression of orotate phosphoribosyl transferase in human pancreatic cancer:
      implication for the efficacy of uracil and tegafur-based adjuvant chemotherapy.
AB  - The enzyme orotate phosphoribosyl transferase (OPRT) is involved in the
      metabolism of the anticancer drug 5-fluorouracil (5-FU), and is a key enzyme for
      conversion of 5-FU to its active form in tumor tissue. Little is known regarding
      the significance of OPRT in human pancreatic cancer. The present study was
      designed to assess the association between the activity of OPRT in the tumor, and
      the clinicopathological status and prognosis of human resectable pancreatic
      cancer, especially regarding its relevance to the efficacy of adjuvant
      chemotherapy with uracil and tegafur (UFT), cyclophosphamide (CPA) and/or
      gemcitabine (GEM). The present study included 99 resectable pancreatic cancers,
      which were all invasive ductal tubular carcinomas. OPRT was immunostained with a
      rabbit anti-human OPRT polyclonal antibody. OPRT was positively stained in 54
      (54.5%) of 99 pancreatic cancers. The post-surgical survival rate of the OPRT (+)
      pancreatic cancers was significantly higher than that of the OPRT (-) ones. In
      the OPRT (+) group, the survival rate of the patients, who received adjuvant
      chemotherapy (ACT) with UFT, CPA or GEM, was significantly higher than that of
      the patients without ACT; however, in the OPRT (-) group, there was no difference
      in the survival between the ACT (+) and (-) groups. Multivariate analyses
      demonstrated that for all patients, primary tumor, status of nodal involvement
      (pN), residual tumor, level of dissection and CPA were significant variables for
      the prognosis: in OPRT (+) groups, primary tumor, nodal involvement, GEM and CPA
      were significant variables. In contrast, in the OPRT (-) group, pN was the only
      significant variable. The present study is the first report on the significance
      of OPRT in human pancreatic cancer, and the results indicate that the expression
      of OPRT may be useful to predict the response to adjuvant chemotherapy in human
      pancreatic cancer.

PMID- 17549347
TI  - X-linked inhibitor of apoptosis (XIAP) and XIAP-associated factor-1 expressions
      and their relationship to apoptosis in human hepatocellular carcinoma and non
      cancerous liver tissues.
AB  - The X-linked inhibitor of apoptosis (XIAP) belongs to the inhibitor of apoptosis
      (IAP) family, and the action of XIAP is inhibited by XIAP-associated factor-1
      (XAF1). In the present study, XIAP and XAF1 protein expressions and their
      relationship to apoptosis were investigated in hepatocellular carcinoma (HCC). We
      examined immunohistochemical expressions of XIAP and XAF1, and the number of
      apoptotic HCC cells in surgically resected tissues of 24 HCCs, consisting of 7
      well-, 10 moderately and 7 poorly differentiated HCCs. As a result, XIAP and XAF1
      expressions were identified in the cytoplasm of non-neoplastic and neoplastic
      hepatocytes. In the 24 HCCs, XIAP expression was not different according to the
      histological grade of HCC. In contrast, XAF1 expression was significantly lower
      in poorly differentiated than that in well- or moderately differentiated HCCs
      (P=0.001), or XIAP expression in poorly differentiated HCC (P<0.001). Apoptotic
      HCC cell number was significantly lower in poorly differentiated than that in
      well- or moderately differentiated HCCs (P<0.01). A significant relationship was
      observed between XAF1 expression and apoptotic cell number in HCC tissues. In
      conclusion, the present findings suggest that significantly low XAF1 expression,
      but not XIAP expression, in poorly differentiated HCC may relate to resistance to
      apoptosis.

PMID- 17549348
TI  - Reactive oxygen species regulate Bax translocation and mitochondrial
      transmembrane potential, a possible mechanism for enhanced TRAIL-induced
      apoptosis by CCCP.
AB  - TRAIL is a TNF family member that engages apoptosis via recruitment and rapid
      activation of caspase-8. Oxygen-free radicals, more generally known as reactive
      oxygen species (ROS) are well recognized for playing an important role in the
      regulation of tumor cell apoptosis. ROS within the cells act as secondary
      messengers in intracellular signalling cascades therefore function as anti
      tumorigenic species. But very little is known about the effect of ROS on TRAIL
      induced apoptosis. In this study we investigated the effect of CCCP, a classic
      uncoupler of oxidative phosphorylation, on TRAIL-induced apoptosis in TRAIL
      resistant MCF-7 cells. It was found that pretreatment with CCCP for 6 h and then
      treatment with TRAIL for additional 3 h markedly enhanced apoptosis by 2-fold as
      compared with TRAIL alone. The uncoupling effect enhanced TRAIL-induced apoptosis
      by ROS generation. Moreover, CCCP treatment also reduced mitochondrial
      transmembrane potential (MTP, Delta Psi m) and induced Bax translocation to the
      mitochondria of its own account. This sensitization was inhibited with N-acetyl-L
      cysteine (NAC) treatment by abrogating the ROS which was generated by the
      combined treatment of CCCP and TRAIL. Of interest, NAC also inhibited reduction
      of the Delta Psi m and Bax translocation after CCCP pretreatment which suggest
      that the generation of ROS may precede the loss in MTP. Thus, we demonstrated
      that CCCP-induced ROS generation enhanced TRAIL induced apoptosis by regulation
      of Bax translocation and mitochondrial transmembrane potential. The enhancing
      effect by CCCP-induced ROS generation was restored after NAC treatment.
      Therefore, our results suggest that uncoupling the cells by CCCP can overcome the
      resistance to TRAIL protein and can be a very efficient treatment for the tumor
      cells especially resistant to TRAIL-induced apoptosis.

PMID- 17549349
TI  - Gamma-secretase inhibitors suppress the growth of leukemia and lymphoma cells.
AB  - gamma-Secretase inhibitors (GSI) suppress the growth of acute T-lymphoblastic
      leukemia (T-ALL) cells with NOTCH1 mutations. Recently, clinical trials of GSI
      for refractory T-ALL have commenced. In the present study, we examined the
      effects of three types of GSI; GSI-I, GSI-IX, and GSI-XII on the growth of four B
      cell malignant lymphoma (B-ML) and four acute myeloid leukemia (AML) cell lines
      as well as four T-ALL cell lines. We found that GSI also suppressed the in vitro
      growth of some B-ML and AML cell lines in a dose-dependent manner. Growth
      suppression occurred through induction of apoptosis. Expression of the HES1 gene,
      one of the targets of Notch signaling, was high in T-ALL cells with NOTCH1
      mutations, but was low in GSI-sensitive B-ML and AML cells. GSI treatment
      decreased HES1 mRNA expression in T-ALL cells, while GSI increased HES1 mRNA in
      two GSI-sensitive B-ML and AML cell lines. In immunoblot analysis, the band for
      the intracellular fragment of Notch1, an active form of Notch1, was dense in T
      ALL cells but was faint in GSI-sensitive B-ML and AML cells; attenuation of the
      band by GSI was not evident. These findings suggest that GSI may act on Notch 2,
      3 or 4 protein, or some pathways other than Notch signaling in GSI-sensitive B-ML
      and AML cells. Namely, growth suppression by GSI may involve cell growth-related
      proteins, which are gamma-secretase substrates. Taken together, we have shown
      that GSI may be useful for the treatment of hematological malignancies other than
      T-ALL. The mechanism behind the effects remains to be clarified. Our
      investigations lead to a novel molecular target therapy for chemotherapy
      resistant leukemia and lymphomas.

PMID- 17549350
TI  - Prognostic significance of expression of nm23-H1 and focal adhesion kinase in non
      small cell lung cancer.
AB  - nm23-H1, a nucleoside diphosphate kinase (NDPK), enhances drug sensitivity and
      has antimetastatic activity, whereas focal adhesion kinase (FAK) is closely
      associated with cell migration and tumour spreading. The relationship between
      these two proteins, however, is not well elucidated. In this study, we
      investigate their correlation in patients with non-small cell lung cancer
      (NSCLC). Expressions of nm23-H1 and FAK were examined by reverse transcription
      polymerase chain reaction and immunoblotting in surgical resections. The
      relationship between these two genes was assessed statistically. Patients were
      classified into four groups according to the expression of nm23-H1 and FAK by
      immunohistochemistry: FAK-negative/nm23-H1-positive, FAK-negative/nm23-H1
      negative, FAK-positive/nm23-H1-positive and FAK-positive/nm23-H1-negative.
      Although the causal correlation is still uncertain, our results showed that
      protein expression of nm23-H1 was inversely correlated with that of FAK. The
      combined analysis of nm23-H1 and FAK protein expression in the same tumour
      specimens revealed that patients with FAK-negative/nm23-H1-positive tumours
      survived the longest, 56 months, among those with nm23-H1 and FAK features
      (P<0.001). Our data indicate that expressions of nm23-H1 and FAK are inversely
      correlated. These results suggest that the status of nm23-H1 and FAK protein
      expression may help in predicting the aggressive behavior of NSCLC. However,
      further studies are warranted to clarify the impact of FAK on the function of
      nm23-H1 as an anti-metastatic gene.

PMID- 17549351
TI  - CDX2 as a useful marker of colorectal adenocarcinoma metastases to lung in pre
      operative biopsy specimens.
AB  - Although distinguishing metastatic colorectal adenocarcinoma from primary lung
      adenocarcinoma is often difficult, pre- or intra-operative identification is very
      important, as the resection areas for each diagnosis differ substantially. CDX2,
      a recently cloned homeobox gene, represents a highly specific and sensitive
      marker of colorectal adenocarcinoma. We evaluated CDX2 expression using pre- and
      intra-operative biopsy specimens. The study examined 50 consecutive colorectal
      adenocarcinoma metastases to the lung, including 20 biopsy specimens and 66
      resected specimens, and 21 primary lung adenocarcinomas. All specimens were
      immunohistochemically stained for CDX2, cytokeratin (CK) 7, CK20 and thyroid
      transcription factor (TTF)-1, and scored in a semi-quantitative manner. Mean
      staining score in biopsy specimens was significantly higher for CDX2 than for
      CK20. Sensitivities for CDX2 and CK7-/20+ in biopsy specimens were 95.0 and
      65.0%, respectively. If CDX2 immunostaining had not been performed, 8 biopsy
      specimens (40%), and 20 resected specimens (30.3%) might have been diagnosed as
      equivocal cases either as primary lung cancer or metastatic colorectal cancer,
      using other markers. These results suggest that positive CDX2 staining represents
      a highly sensitive and specific marker of metastatic colorectal carcinoma in both
      biopsy and resected specimens, and is superior to staining for the CK7-/20+
      phenotype.

PMID- 17549352
TI  - Elevated N-myristoyltransferase activity and expression in oral squamous cell
      carcinoma.
AB  - N-myristoyltransferase (NMT) catalyzes the myristoylation of proteins involved in
      signal transduction, cellular transformation, differentiation, proliferation and
      oncogenesis. In this study, we report for the first time on the elevated NMT
      activity in oral squamous cell carcinoma (OSCC). Increased activity is marked
      with increased staining for NMT in the OSCC samples compared to the normal
      adjacent tissues. In addition, we observed increased staining for the N
      myristoyltransferase inhibitor protein 71 (NIP71) in the OSCC samples compared to
      the control tissues. These findings suggest the regulatory relationship between
      NMT and NIP71 during tumorigenesis. It is possible that the increased activity
      results in the overexpression of NIP71 in an effort to control NMT activity.

PMID- 17549353
TI  - Overexpression of cysteinyl LT1 receptor in prostate cancer and CysLT1R
      antagonist inhibits prostate cancer cell growth through apoptosis.
AB  - The metabolism of arachidonic acid by either cyclooxygenase or lipoxygenase is
      believed to play an important role in carcinogenesis. Leukotriene (LT) D4 is a
      proinflammmatory mediator derived from arachidonic acid through various enzymatic
      steps, and 5-lipoxygenase is an important factor in generating LTD4. We
      investigated LTD4 receptor (cysteinyl LT1 receptor: CysLT1R) expression in
      prostate cancer (PC), as well as the effects of CysLT1R antagonist on cell
      proliferation in PC cell lines. CysLT1R expression in PC patients, prostatic
      intraepithelial neoplasia (PIN), benign prostatic hyperplasia (BPH), and normal
      prostate (NP) tissues were examined. CysLT1R expression was detected by
      immunohistochemistry. Effects of CysLT1R antagonist on PC cell growth were
      examined by MTT assay. Flow cytometry and Hoechst staining were used to determine
      whether or not the CysLT1R antagonist induces apoptosis. Initially, only slight
      CysLT1R expression was detected in BPH and NP tissues and marked CysLT1R
      expression was detected in PIN and PC tissues. CysLT1R expression was higher in
      high-grade cancer than in low-grade cancer. Furthermore, CysLT1R antagonist
      caused marked inhibition of PC cells in a concentration- and time-dependent
      manner through early apoptosis. In conclusion, CysLT1R is induced in PC, and the
      results suggest that CysLT1R antagonist may mediate potent anti-proliferative
      effects of PC cells. Thus, the target of CysLT1R may become a new therapy in the
      treatment of PC.

PMID- 17549354
TI  - RAR beta2 suppression in head and neck squamous cell carcinoma correlates with
      site, histology and age.
AB  - Retinoids as important growth and differentiation regulating agents have a
      potential role in the chemoprevention of head and neck squamous cell carcinoma
      (HNSCC). Despite the promising preclinical and early clinical findings,
      limitations of application are raised by intrinsic resistance acquired during
      carcinogenesis. Retinoic acid receptor beta2 (RAR beta2) is one of the proximate
      mediators of retinoid signalling and its expression is often diminished in early
      stages of head and neck carcinogenesis. One form of retinoid resistance has been
      associated with the methylation-induced silencing of the RAR beta gene. We
      studied primary HNSCC samples of different anatomical sites in respect of
      methylation, expression and allelic loss of RAR beta gene. A strong correlation
      (p<0.01) was found between hyper-methylation and reduced expression of RAR beta2,
      however the allelic loss at 3p24, the locus of RAR beta, did not considerably
      influence its mRNA level. Hypopharynx tumors showed significantly lower
      hypermethylation (p<0.05) and higher mRNA expression levels of RAR beta2 compared
      to the tumors located at other sites of the head and neck. We could also provide
      evidence that poorly differentiated grade 3 tumors had significantly higher RAR
      beta2 expression and lower methylation levels (p<0.05) than better differentiated
      grade 1 and grade 2 tumors. In addition, we found a good correlation between the
      methylation degree of the RAR beta2 promoter and the ages of patients.
      Collectively, our results suggest that evaluation of several factors such as
      tumor location, age, histology and methylation state of the RAR beta gene might
      contribute to the selection of patients for retinoid-based chemoprevention.

PMID- 17549355
TI  - The effect of chemotherapy on Ki-67, Bcl-2 and Bak expression in primary tumors
      and lymph node metastases of breast cancer.
AB  - The aim of this study was the analysis of Ki-67, Bcl-2 and Bak expression in
      primary tumor and axillary lymph node metastases of breast cancer as well as an
      attempt to assess preoperative chemotherapy influence on the mentioned markers
      with regard to changes in the morphological appearance of the primary tumor and
      its metastases. Immunohistochemical examinations of Ki-67, Bcl-2 and Bak
      expression were conducted on sections collected from 135 patients treated
      surgically on invasive ductal breast cancer. Sixty-four of these patients were
      administered preoperative chemotherapy, whilst on 71 patients the surgery was
      performed without initial chemotherapy. In the group of patients without
      preoperative chemotherapy positive correlation in Ki-67 and Bcl-2 expression
      between primary tumors and lymph node metastases (p<0.0001, r=0.707; p<0.0001,
      r=0.604, respectively) was observed. In the group of patients after chemotherapy
      positive correlation between primary tumors and lymph node metastases in case of
      Bcl-2 and Bak proteins (p<0.04, r=0.424; p<0.02, r=0.478, respectively) was
      observed. It was also found that preoperative chemotherapy has an influence on
      the expression of proteins connected with proliferation and apoptosis and thus,
      it can influence neoplastic process biology. It does not have any significant
      impact on the proapoptotic Bak protein expression either in primary tumor or in
      lymph node metastases of breast cancer. However, it is related to lower
      expression of antiapoptotic Bcl-2 protein (p<0.0005) and of Ki-67 proliferation
      marker (p<0.03) in primary tumors, which indirectly indicates a beneficial
      influence of preoperative chemotherapy on the primary tumor. Concurrently, the
      influence of neoadjuvant therapy on lymph node metastases seems to be relatively
      small, which can limit its effectiveness.

PMID- 17549356
TI  - C-erbB-2 expression is a better predictor for survival than galectin-3 or p53 in
      early-stage breast cancer.
AB  - The definition of high risk patients with early stage breast cancer is still
      controversial. We evaluated the ability of galectin-3, c-erbB-2 and p53
      immunohistochemical expression to predict recurrence and survival in a
      homogeneous set of 92 patients with T1N0M0 ductal carcinoma with a long-term
      follow-up. In normal breast tissue, the epithelial and fibroblast components were
      positive for galectin-3 mostly showing nuclear and cytoplasmic reactivity. At the
      tumor epithelial component, galectin-3 expression was found in 46.7% of the
      samples with a predominant cytoplasmic staining. Similar results were presented
      by concurrent in situ lesions. Tumor stromal fibroblasts maintained positivity in
      70 out of 92 cases (76%). We found expression of p53 in only 16 cases (17.4%),
      and c-erbB-2 in 17 (18.48%). A marginal association was found between co
      expression of p53 and galectin-3 (p=0.055) and a significant correlation between
      p53 accumulation and c-erbB-2 expression (p=0.009). There was no significant
      association between galectin-3 protein expression with disease-free survival or
      overall survival. C-erbB2 and p53 expression correlated with recurrence (p=0.002,
      p=0.02; respectively). Diminished overall survival at 10 years was associated
      with c-erbB-2 (p=0.010), but marginally with p53 expression (p=0.076). Epithelial
      galectin-3 expression cannot be considered a prognostic factor for patients with
      T1N0M0 breast cancer, p53 seems to be of minor relevance and c-erbB-2 expression
      was the best discriminator and may be a marker for aggressive clinical behavior
      in patients with early stage breast cancer.

PMID- 17549357
TI  - Differential methylation of the OCT3/4 upstream region in primary human
      testicular germ cell tumors.
AB  - Germ cell tumors show many similarities to normal embryogenesis. This is, for
      example, illustrated by the expression of the marker of pluripotency, OCT3/4,
      known to play a pivotal role in the early stages of normal development.
      Interestingly, it is found to be the most informative diagnostic marker for the
      early developmental stages of malignant germ cell tumors. Expression regulation
      of OCT3/4 has been extensively studied in murine and human cell lines, including
      embryonic stem cell lines and tumor derived cell lines. We investigated for the
      first time the methylation status of the upstream region of the OCT3/4 gene in
      normal and neoplastic testicular primary tissues using bisulfite genomic
      sequencing. The cell line JKT-1, supposedly seminoma-derived, was included in the
      survey. Normal testis parenchyma, peripheral blood lymphocytes, spermatocytic
      seminoma, yolk sac tumor and teratoma, and JKT-1 showed a consistent
      hypermethylation. In contrast, seminoma and embryonal carcinoma were
      hypomethylated, confirmed by analyses after tumor micro-dissection. Testicular
      lymphomas showed the most heterogeneous pattern, although specific regions were
      consistently hypermethylated. In conclusion, the results obtained from this set
      of adult normal and neoplastic in vivo derived samples is in accordance to the in
      vitro data that expression of OCT3/4 is associated with specific changes in
      methylation. Moreover, the findings argue against OCT3/4 being a driving
      oncogenic factor in the pathogenesis of human germ cell tumors.

PMID- 17549358
TI  - The role of the endothelin axis and microvessel density in bladder cancer -
      correlation with tumor angiogenesis and clinical prognosis.
AB  - Endothelin-1 (ET-1) and its receptors, entothelin-A (ETAR) and endothelin-B
      (ETBR), commonly referred to as the endothelin (ET)-axis, are involved in tumor
      biology and growth. We investigated the effects of the ET-axis on microvessel
      density (MVD) and the clinicopathological parameters of patients with invasive
      bladder cancer. Paraffin tumor sections of 120 patients who had undergone radical
      cystectomy were assessed immunohistochemically using mono- and polyclonal
      antibodies for ET-1, ETAR, ETBR and CD34 (MVD). Staining intensities were
      analyzed semiquantitatively and the MVD was calculated as vessels per field. The
      results were correlated with various pathological and clinical factors, as well
      as with disease-free and overall survival. Transitional cell carcinomas
      (MVD=23.7) were better vascularized than squamous cell carcinomas (MVD=17.8,
      p=0.04). Organ-confined tumors (MVD=32.2) were better vascularized than T3- and
      T4-tumors (MVD=21.2, p=0.02) and ET-1 was overexpressed in this subgroup
      (p=0.027). Patients with metastatic regional lymph nodes (MVD=20.9) tended to
      have less MVD than patients without regional lymph node metastases (MVD=24.1)
      (p=0.15). The account of MVD did not reveal any significant differences in
      disease-free or overall survival. Organ-confined tumors and ET-1 overexpression
      are associated with upregulated microvessel density. These results suggest that
      MVD and ET-1 could be considered good prognostic factors.

PMID- 17549359
TI  - Activated Akt signaling pathway in invasive ductal carcinoma of the breast:
      correlation with HER2 overexpression.
AB  - Akt/PKB is a serine/threonine kinase that plays a crucial role in cell survival
      and apoptosis. Aberrant activation of pAkt is associated with various malignant
      human cancers, including breast carcinoma. In vitro studies show that pAkt
      activation is mediated by estrogen and acts as a downstream effector of HER2 with
      implications in breast cancer progression and drug resistance. We investigated
      the incidence of Akt activation in invasive ductal carcinoma and its correlation
      with other clinicopathological variables. Using tissue microarray technology,
      immunohistochemical expression of phosphorylated Akt (pAkt) at Ser-473 was
      evaluated in 127 cases of invasive ductal carcinomas, together with hormone
      receptors, HER2, p53, Ki-67 and other clinicopathological variables. Both nuclear
      and cytoplasmic expression was noted for pAkt, with 46 cases (36.2%) showing high
      cytoplasmic pAkt expression and 37 cases (29.1%) showing high nuclear pAkt
      expression. There was a significant association between both high cytoplasmic and
      nuclear pAkt expression with HER2 overexpression (both p<0.0001). There was also
      a positive correlation between high nuclear pAkt expression with both estrogen
      receptor and progesterone receptor status (p=0.042 and p=0.015, respectively).
      High cytoplasmic pAkt expression was associated with high Ki-67 expression
      (p=0.052), however, there was no association between pAkt and p53 expression. In
      the present study, activation of the Akt pathway shows strong association with
      HER2 overexpression, which is consistent with many in vitro studies. Our study
      also showed a positive correlation between pAkt and hormone receptors, which
      suggested the possible mechanism of endocrine resistance in ER-positive breast
      cancer. These results also suggest the prognostic value of pAkt and its
      importance in the prediction of therapeutic response in invasive ductal carcinoma
      of the breast.

PMID- 17549360
TI  - Plasma levels and expression of vascular endothelial growth factor-A in human
      localized prostate cancer.
AB  - Although the impact of vascular endothelial growth factor (VEGF) is clearly
      established in advanced prostate cancer (PCa), its role in localized PCa remains
      to be determined. The aim of our study was to analyse the plasma levels of VEGF-A
      and the expression of VEGF-A in prostatic tissue in a population of patients with
      localized PCa. We measured the preoperative plasma levels of VEGF-A in 100
      patients undergoing radical prostatectomy (RP) for clinically-localized PCa.
      After intervention, we determined the expression of VEGF-A in all RP specimens
      using immunohistochemistry. We found no association between plasma levels of VEGF
      A and the established prognostic factors of PCa. Moreover, there was no
      association between plasma levels of VEGF-A and the expression of VEGF-A in
      prostatic tissue. On the contrary, there was a strong correlation between the
      expression of VEGF-A in PCa tissue and the Gleason score of cancer: the
      expression of VEGF-A was significantly higher in patients with a high Gleason
      score on RP specimen (p=0.01). Our results suggest that the expression of VEGF
      may have a prognostic impact in clinically-localized PCa.

PMID- 17549361
TI  - Coexpression of EGFR and HER-2 in pancreatic ductal adenocarcinoma: a comparative
      study using immunohistochemistry correlated with gene amplification by
      fluorescencent in situ hybridization.
AB  - Pancreatic ductal adenocarcinoma (PDAC) is the major pancreatic tumor and carries
      an extremely poor prognosis. Coexpression of epidermal growth factor receptor
      (EGFR) and the HER-2 oncoprotein has been reported to be related to the invasion
      and an adverse clinical outcome of human pancreatic ductal adenocarcinomas. HER-2
      amplification, as determined by fluorescent in situ hybridization (FISH)
      analysis, has been identified as a positive predictor of response to EGFR
      tyrosine kinase inhibitor treatment in some other cancers. The aim of this study
      was to investigate the coexpression rate and amplification status of HER-2
      oncogene in EGFR positive pancreatic ductal adenocarcinoma (PDAC) by
      immunohistochemistry and FISH. Overexpression of EGFR (>or=2+) was seen in 65%
      (21/32) of the study cases. EGFR gene amplification was not detected in any of
      the 32 PDACs. Overexpression of HER-2 protein (>or=2+) was seen in 17% (5/28) of
      the study cases and in 24% (5/21) of EGFR positive cases. None of the EGFR
      negative tumors showed HER-2 overexpression or gene amplification. The HER-2 gene
      locus was amplified in 11% (3/28) of the study cases and in 14% (3/21) of EGFR
      positive PDACs. There was 60% concurrence between HER-2 gene amplification and
      HER-2 protein expression in this study. These results suggest that HER-2 is an
      important cooperating member of the EGFR signal pathway in a subset of PDAC.

PMID- 17549362
TI  - A comparison of liquid-based cytology and Pap smear as a screening method for
      cervical cancer.
AB  - The implementation of population-based screening for cervical cancer with Pap
      smear in the early sixties was set to detect and treat precancerous lesions,
      hopefully preventing a subsequent invasive cervical cancer. Epidemiological data
      indicate that organized screening has a major impact on morbidity and mortality
      from cervical cancer. The limited sensitivity of a single smear necessitates
      repeated smears in organized program. It is suggested that liquid-based cytology
      improves the sensitivity. The aim of this split-sample study was to compare
      ThinPrep liquid-based cytology with conventional Pap smear, relying on a
      laboratory with long-term experience of the latter. In total, 137 women with
      atypical Pap smear in population-based cervical screening were enrolled for the
      split-sample study. The performance of both techniques (ThinPrep liquid-based
      cytology and conventional Pap smear) were compared and validated by a
      histological follow-up. Women without representative histological biopsy were
      excluded from the study. Pap smear had sensitivity for detection of CIN2-3 of 47%
      compared to 66% for liquid-based material. The concordance of the two sampling
      techniques with the histological diagnosis was 37% and 53%, respectively, this
      difference being statistically significant. The proportion of reports on atypical
      squamous cells of undetermined significance (ASCUS) was significantly less in the
      liquid-based material, 4.3% compared to 8% of the conventional smears. This
      improved sensitivity in combination with the possibility to perform reflex
      testing such as HPV DNA or p16 immunocytochemistry without renewed sampling gives
      ThinPrep a substantial advantage and makes the liquid-based technique
      interesting.

PMID- 17549363
TI  - Increased levels of IgG antibodies against peptides of the prostate stem cell
      antigen in the plasma of pancreatic cancer patients.
AB  - One of the longstanding challenges in the treatment of pancreatic cancer, the
      fifth most common cancer worldwide, is to establish a simple and reliable
      diagnostic marker for the disease. This study examined whether or not the plasma
      levels of IgG antibodies (IgGs) reactive to peptides derived from the prostate
      stem cell antigen (PSCA), which is highly expressed in pancreatic cancer cells,
      were elevated in patients with pancreatic cancer. Fifty-seven kinds of peptides
      encoded by PSCA were tested for their reactivity to plasma IgGs of pancreatic
      cancer patients. The results showed that the levels of IgGs specific to each of
      the 10 different peptides in the plasma of pancreatic cancer patients were
      significantly higher than those of non-cancer subjects. Eighty percent of
      subjects with and 18% of subjects without pancreatic cancer were diagnosed as
      having pancreatic cancer, respectively, when those cases showing significantly
      elevated levels of IgGs against at least one of the three peptides of PSCA at
      positions 2-11, 85-95, and 109-118 were judged as positive for pancreatic cancer.
      These results indicate that the measurement of IgGs reactive to these PSCA
      derived peptides can provide novel information on the host-tumor interaction in
      pancreatic cancer, and could potentially be used as a new diagnostic tool to
      screen for pancreatic cancer.

PMID- 17549364
TI  - Anti-progestins suppress the growth of established tumors induced by 7,12
      dimethylbenz(a)anthracene: comparison between RU486 and a new 21-substituted-19
      nor-progestin.
AB  - In this report, we evaluate the effects of a 21-substituted-19-nor-progestin, CDB
      4124, on 7,12,-dimethylbenz(a)anthracene (DMBA)-induced mammary carcinogenesis in
      rats in comparison with RU486. Sprague-Dawley female rats were treated with DMBA
      at 50 days of age in order to induce mammary tumors. When the tumors reached the
      size of 10-12 mm, the animals were treated for 28 days with the vehicle, RU486,
      progesterone, CDB-4124 at various doses, or CDB-4124 plus progesterone. Anti
      progestins resulted in the regression in the size of the existing tumors, and in
      the suppressed development of new tumors and tumor multiplicity. Progesterone
      treatment, however, increased the size and multiplicity. Progesterone rendered an
      increased number of growing tumors as compared to the regression in the anti
      progesterone treatment groups. The combination of CDB-4124 and high doses of
      progesterone opposed the efficacy of CDB-4124. The growth inhibitory effects of
      the anti-progestins were correlated with increased apoptosis and reduced cell
      proliferation. These results indicate that anti-progestins should be developed
      for the chemoprevention and treatment of hormone-responsive breast cancer.

PMID- 17549365
TI  - E-cadherin increases squamous cell carcinoma antigen expression through
      phosphatidylinositol-3 kinase-Akt pathway in squamous cell carcinoma cell lines.
AB  - Squamous cell carcinoma antigen (SCCA) has been used for the management of
      squamous cell carcinoma, especially for evaluating therapeutic effects and
      monitoring recurrence. It has been reported that SCCA has several biological
      activities and influences behavior of cancer cells. E-cadherin is a cell adhesion
      molecule and plays important roles in the process of cancer invasion and
      metastasis. Our previous studies have shown that blockage of E-cadherin action by
      anti-E-cadherin antibody treatment suppresses SCCA production in squamous cell
      carcinoma cells. This finding strongly suggests that E-cadherin regulates SCCA
      expression. The present study was, therefore, undertaken to investigate the
      correlation between E-cadherin and SCCA2. For this purpose, E-cadherin cDNA was
      transfected into squamous cell carcinoma cell lines, SiHa and SKG IIIa.
      Overexpression of E-cadherin increased SCCA2 expression together with cell
      aggregation. We also examined the involvement of phosphatidylinositol 3-kinase
      (PI3K)-Akt pathway, which is one of major signaling pathways from E-cadherin. E
      cadherin transfection increased phosphorylated Akt expression concomitantly with
      the increase in SCCA2 expression, and the increased SCCA2 expression was
      inhibited by a PI3K inhibitor. In conclusion, SCCA2 is up-regulated by E-cadherin
      through PI3K-Akt pathway, suggesting that SCCA2, as well as E-cadherin, may be
      involved in the regulation of cancer behavior.

PMID- 17549366
TI  - Induction of apoptosis by isothiocyanate sulforaphane in human cervical carcinoma
      HeLa and hepatocarcinoma HepG2 cells through activation of caspase-3.
AB  - Sulforaphane (SFN) is an isothiocyanate that is found in abundant quantities in
      many cruciferous vegetables including broccoli and cauliflower. Its inhibitory
      effects on tumor cell growth in vitro and in vivo, which is dependent on the
      direct effect on cancer cells, has attracted considerable attention. This study
      examined the effects of SFN on the growth of human cervical carcinoma HeLa and
      hepatocarcinoma HepG2 cells. The results showed that SFN inhibits the viability
      of both HeLa and HepG2 cells by inducing apoptosis, as evidenced by the formation
      of apoptotic bodies and the accumulation of the sub-G1 phase. RT-PCR and
      immunoblotting showed that treating the cells with SFN caused the down-regulation
      of anti-apoptotic Bcl-2 and Bcl-XL, and the up-regulation of pro-apoptotic Bax
      expression. SFN-induced apoptosis was associated with the proteolytic activation
      of caspase-3, and the degradation/cleavage of poly (ADP-ribose) polymerase and
      the beta-catenin protein. z-DEVD-fmk, a caspase-3 specific inhibitor, blocked the
      activation of caspase-3 and increased the survival of the SFN-treated HeLa and
      HepG3 cells, suggesting that caspase-3 activation is essential for SFN-induced
      apoptosis.

PMID- 17549367
TI  - Repeat reduction surgery after an initial hepatectomy for patients with
      colorectal cancer.
AB  - A hepatectomy is the only treatment offering long-term survival in patients with
      colorectal liver metastases. However, 70-80% of the patients with a complete
      resection develop recurrent disease after an initial hepatectomy. Sixty-one
      patients who underwent metastases from colorectal carcinoma with a curative
      hepatectomy were entered into this study. Recurrence after hepatectomy was
      observed in 41 patients (67.2%). We reviewed the outcome of these 41 patients.
      Repeat reduction surgery was performed on 16 out of 41 patients (39.0%).
      According to a multivariate analysis, repeat reduction surgery and tumor size
      were found to be independent prognostic factors for the survival rate (p=0.007,
      p=0.018). Furthermore, in the group that underwent repeat reduction surgery, the
      rate of positive lymph nodes was significantly lower in the primary lesions, and
      the disease-free interval (DFI) was also significantly longer than in the group
      that did not undergo repeat reduction surgery (p=0.023, p=0.045), respectively.
      Repeat reduction surgery was found to be the most important prognostic factor.
      Patients with a longer DFI and with negative lymph node findings at the primary
      site may therefore be considered to be good candidates for repeat reduction
      surgery.

PMID- 17549368
TI  - Differential regulation of the cytotoxicity activity of paclitaxel by orobol and
      platelet derived growth factor in human ovarian carcinoma cells.
AB  - Paclitaxel (PX) binds to and stabilizes tubulin, preventing depolymerization, and
      resulting in cell death. Based on a previous report showing the activity of
      phosphatidylinositol kinase (PIK) on tubulin, we investigated the effect of the
      PI4K inhibitor orobol and the PI3K activator platelet derived growth factor
      (PDGF) on PX sensitivity. Drug sensitivity was examined by classical colony
      forming assay. Tubulin isotype expression was determined by semi-quantitative RT
      PCR. Microtubule texture was observed by laser confocal microscope using anti
      beta-tubulin antibody. Apoptotic activity was estimated by frequency of condensed
      nuclear chromatin with Hoechst 33342 stain. Orobol enhanced PX sensitivity of
      human ovarian carcinoma 2008 cells by 18.9+/-1.2-fold (N=3; P<0.01). In contrast,
      pretreatment with PDGF rendered cells resistant to PX by 2.3+/-0.4-fold (N=3;
      P<0.01). Neither orobol nor PDGF showed any effect on cell growth. Orobol
      produced a 2.5-fold sensitization in cisplatin-resistant 2008/C13*5.25 (C13)
      cells, and PDGF rendered the cells 2.3-fold resistant to PX. Orobol suppressed
      the beta 4a-tubulin isotype expression by 85% and other isotypes by 20%. In
      contrast, PDGF induced beta 4a-tubulin isotype expression by 1.3-fold, while it
      supressed all the other isotypes by 20-40%. Orobol produced thick microtubules
      and PDGF generated ring condensed microtubules. Orobol promoted PX-induced
      apoptosis, while PDGF caused 50% reduction of apoptosis. These results indicate
      that orobol and PDGF regulate PX sensitivity by reciprocally altering the
      proportion of tubulin isotype expression and PX-induced apoptotic signaling.

PMID- 17549369
TI  - Do thymidylate synthase gene promoter polymorphism and the C/G single nucleotide
      polymorphism predict effectiveness of adjuvant 5-fluorouracil-based chemotherapy
      in stage III colonic adenocarcinoma?
AB  - Since 5-fluorouracil (5-FU)-based chemotherapy has become standard adjuvant
      treatment for patients with node-positive colonic adenocarcinoma, there has
      arisen the need for predictive factors. Thymidylate synthase (TS) is a major
      target of 5-FU's action, and high TS expression in carcinoma cells could reduce
      its cytostatic effect. Both, a 28-base pair repeat polymorphism and a cytosine
      vs. guanine single nucleotide polymorphism in the promoter region of the TS gene
      are known to modulate its expression. All patients with a single, non
      metachronous node-positive colonic adenocarcinoma who underwent a potentially
      curative resection at this institution in the years 1994-2002, and who received
      adjuvant 5-FU (n=95) were included in this study. Ninety-four of the 95 patients
      were successfully genotyped: 70 patients were classified as TS gene low
      expressors (2R-2R, 2R-3C and 3C-3C), and 24 patients were classified as high
      expressors (2R-3G, 3C-3G and 3G-3G). Contrary to the hypothesis, Kaplan-Meier
      survival analysis did not reveal any differences between the groups (power of 0.8
      to detect an absolute survival difference >30%). In a Cox model, venous
      angioinvasion and the infiltrative pattern of tumour invasion were strong adverse
      factors. These results argue against a practical role for the TS gene repeat
      polymorphism or the C/G single nucleotide polymorphism as a predictive factor.
      However, by careful histopathological examination a high-risk group of node
      positive patients can be defined that could be candidates for studies of
      alternative (more aggressive) adjuvant treatment.

PMID- 17549370
TI  - A polymorphism C3435T of the MDR-1 gene associated with smoking or high body mass
      index increases the risk of sporadic breast cancer in women.
AB  - The human multidrug resistance gene 1 (MDR-1) encodes a plasma membrane P
      glycoprotein (P-gp) that functions as the transmembrane efflux pump for various
      structurally unrelated anticancer agents and toxins. Polymorphisms in the MDR-1
      gene may have an impact on the expression and function of P-gp, thereby
      influencing the susceptibility to various diseases, including cancer. We
      investigated the incidence of C3435T polymorphisms at exon 26 in the MDR-1 gene
      in 92 women with breast cancer and potential association of altered genotypes
      with smoking and high body mass index in cancer development among patients. The
      MDR-1C3435T allelotype and genotype analysis revealed a high incidence (75.0%) of
      polymorph alteration in the MDR-1 gene. The frequencies of homozygous T/T,
      heterozygous C/T and homozygous C/C genotypes were 25.0, 50.0 and 25.0%,
      respectively. The risk of breast carcinoma in patients with MDR-1 polymorphism
      was significantly associated with the higher body mass index, where women with
      BMI >30 kg/m(2) and C allele in genotype had a higher risk of disease compared to
      patients with lower amounts of body fat tissue (p=0.0439). The risk was highest
      for the homozygous carriers of C allele with BMI >30 kg/m(2) compared to patients
      with BMI 25.1-30 or <or=25 kg/m(2) (OR 3.65, 95% CI 0.94-14.20; or OR 2.50, 95%
      CI 0.55-11.41), respectively. Consistent with the results of genotyping and BMI
      analyses, smoking patients harboring the C/T or C/C genotype had an increased
      risk of cancer (OR 1.28, 95% CI 0.23-7.17; OR 1.58, 95% CI 0.28-10.44,
      respectively) when exposed to carcinogens in tobacco smoke, although it was not
      statistically significant. Our findings suggest that the MDR-1C3435T polymorphism
      occurs in high incidence among women with breast carcinoma where C allele
      carriers have increased risk of developing cancer when exposed to toxic
      substances. Our observations are the first that indicate this polymorphism as a
      modulator of health to be associated with an increased risk of breast cancer.

PMID- 17549371
TI  - Effect of 41 degrees C and 43 degrees C on cisplatin radiosensitization in two
      human carcinoma cell lines with different sensitivities for cisplatin.
AB  - The effect of trimodality treatment consisting of hyperthermia, cisplatin and
      radiation was investigated in two cell lines with different sensitivities to
      cisplatin. Hyperthermia treatment was performed for 1 h at 41 degrees C and 43
      degrees C in order to compare the effects of the two temperatures. Clonogenic
      assays were performed with cisplatin-sensitive SiHa human cervical carcinoma and
      cisplatin-resistant SW-1573 human lung carcinoma cell lines. Cells were treated
      with various combinations of hyperthermia, cisplatin and radiation. Radiation was
      performed after 1 h of simultaneous hyperthermia and cisplatin treatment.
      Cisplatin exposure was for 1 h or continuous without refreshment of the cisplatin
      containing medium. SiHa cells were more sensitive to cisplatin than SW-1573
      cells. Hyperthermia at 41 degrees C decreased survival in SW-1573 cells but was
      not cytotoxic in SiHa cells. Hyperthermia at 43 degrees C decreased survival
      dramatically in both cell lines with SiHa being the most sensitive. The addition
      of hyperthermia at 41 degrees C and 43 degrees C to cisplatin treatment led to
      enhanced cell kill in both cell lines compared with cisplatin alone.
      Radiosensitization was observed after continuous but not after 1 h of cisplatin
      treatment. Hyperthermia at 43 degrees C increased radiosensitivity whereas
      hyperthermia at 41 degrees C did not. A combination of 41 degrees C hyperthermia
      with continuous cisplatin treatment had an additive effect on SW-1573 cells but
      enhanced cisplatin radiosensitivity of SiHa cells. In SW-1573 cells trimodality
      treatment using 43 degrees C hyperthermia enhances cisplatin radiosensitivity. We
      conclude that hyperthermia at 43 degrees C enhances cisplatin-induced
      radiosensitization in both cisplatin-sensitive and -resistant cell lines.
      Hyperthermia at 41 degrees C was also able to increase cisplatin-induced
      radiosensitivity but only in the cisplatin-sensitive SiHa cell line.

PMID- 17549372
TI  - Anti-proliferative and antioxidant activities of Saposhnikovia divaricata.
AB  - The dry root of Saposhnikovia divaricata (Turcz.) Schischk. (SD, syn.
      Ledebouriella divaricata (Turcz.); Umbelliferae), Siler, a perennial herb of the
      carrot family, is also known as Fang Feng in traditional Chinese herbal medicine.
      It is a herbal ingredient included in many polyherb formulae. This study
      investigated the in vitro anti-proliferative, antioxidant and anti-inflammatory
      activities of the SD extract (1 g/10 ml 70% ethanol). IC50 (50% inhibition) is
      estimated at 1/300, 1/1400, 1/250 and 1/600 dilutions, for the K562, HL60, MCF7
      and MDA-MB-468 cell lines, respectively. The combination of non-cytotoxic
      concentrations of SD with chemotherapeutic drugs such as camptothecin or
      paclitaxel showed additive anti-proliferative effects on K562, HL60 and MCF7
      cells, and antagonistic effects on MDA-MB-468 cells. At a dilution of 1/2000, SD
      induced a differentiation of 17.5+/-2.5% in HL60 cells along the granulocyte
      lineage compared to 2.8+/-0.8% in the untreated controls, but not along the
      monocyte/macrophage lineage. At non-cytotoxic 1/10000, 1/5000 and 1/2000
      dilutions, the SD extract did not affect nitric oxide (NO) production by non
      stimulated RAW 264.7 cells, but dose-dependently and significantly reduced NO
      production by lipopolysaccharide (LPS)-activated RAW 264.7 cells. RT-PCR analyses
      showed that SD at a dilution of 1/2000 did not affect TNFalpha, IL-1 beta, iNOS
      and COX-2 mRNA expression in RAW 264.7 cells compared to the unstimulated
      controls, but significantly reduced (p<0.05) iNOS and its mRNA expression in LPS
      activated cells. It is concluded that the SD ethanol extract possesses strong
      anti-proliferative properties against several human tumor cell lines, a mild
      granulocyte differentiation inducing property on HL60 cells, and potent
      antioxidant, anti-inflammatory and protective properties on LPS-activated RAW
      264.7 cells. Further research is required in order to identify the major
      ingredients present in the Saposhnikovia divaricata root and rhizome showing the
      observed activities.

PMID- 17549373
TI  - Association of polymorphisms in myeloperoxidase and catalase genes with
      precancerous changes in the gastric mucosa of patients at inner-city hospitals in
      New York.
AB  - Gastric carcinogenesis is a multistep process progressing from chronic gastritis,
      through glandular atrophy (GA), intestinal metaplasia (IM) and dysplasia. We have
      previously demonstrated that minority patients at New York City hospitals are
      infected with a relatively virulent strain of H. pylori (Hp) and that Hp
      infection is associated with an increased incidence of precancerous changes in
      the gastric mucosa. Nevertheless, precancerous changes are not observed in every
      Hp-infected individual, suggesting that environmental and genetic factors may
      also play a role in the formation and appearance of precancerous lesions. In the
      present study, the association between polymorphisms in the promoter regions of
      human myeloperoxidase (MPO -463G--> A) and catalase (CAT -262C-->T) genes and the
      appearance of precancerous changes in the gastric mucosa of our patient
      population were examined. Patients enrolled in this study were undergoing
      endoscopy for gastrointestinal complaints. Samples were collected from 126
      patients at Kings County Hospital in Brooklyn and St. John's Episcopal Hospital
      in Queens. One antral biopsy was taken for genotyping, while additional biopsies
      were taken from the antrum and fundic region for histological analysis and were
      scored with respect to acute and chronic inflammation, GA, IM and Hp infestation
      according to the Sydney classification. MPO and CAT genotypes were determined by
      PCR and RFLP. CAT genotypes did not influence the incidence or severity of
      precancerous lesions in the fundic or antral regions of the stomach, whereas the
      MPO -463A allele was associated with an increase in intensity of gastric atrophy
      in the fundic mucosa. In Hp-infected individuals, the MPO -463G/G genotype was
      associated with an increase in the incidence of IM in the antrum, whereas the A
      allele was associated with an increase in IM in the fundic region. These
      paradoxical findings suggest that different MPO genotypes are associated with the
      appearance of IM in distinct anatomical regions of the stomach. However, since
      the majority of gastric cancer (GC) cases in our patient population occurred in
      the antrum, the MPO -463G/G genotype, which is associated with increased MPO
      expression and antral IM, may be considered a risk factor for GC.

PMID- 17549374
TI  - VEGF-C, VEGFR-3, and COX-2 enhances growth and metastasis of human cervical
      carcinoma cell lines in vitro.
AB  - The study was conducted to clarify the expression and biological significance of
      VEGF-C and VEGFR-3 in human cervical cancer cell lines and to investigate the
      correlation between VEGF-C and cyclooxygenase-2 (COX-2) expression in these
      cells. Flow cytometry, Western blotting, RT-PCR, cell immunochemistry assay, cell
      proliferation assay, in vitro invasion assay and cell immunochemistry assay were
      used to detect the gene expression and to evaluate the biological features in
      test cell lines. VEGF-C expression was low while VEGFR-3 was quiet high in all
      cell lines detected. COX-2 expression coincided with that of VEGF-C. Recombinant
      human VEFG-C-treated HeLa cells showed increased proliferation and invasion in a
      dose-depended manner while NS398, a specific inhibitor of COX-2, blocked the
      invasive ability of HeLa. VEGF-C and its VEGFR-3 played a crucial role in the
      regulation of tumor growth and metastasis in cervical cell lines, and COX-2 might
      be a regulator of VEGF-C expression.

PMID- 17549375
TI  - Expression study of the target receptor tyrosine kinase of Imatinib mesylate in
      skull base chordomas.
AB  - Chordomas are rare neoplasms arising along the axial skeleton. Up to now, the
      most suitable therapeutic approach is based on a combination of surgical excision
      and radiotherapy. Chemotherapy in not applied due to its reported low efficacy.
      Recently, evidence on the efficacy of Imatinib mesylate in two patients has been
      reported. We analyzed 14 chordoma samples for the expression of the Imatinib
      mesylate targets by means of RT-PCR and immunohistochemistry and found that PDGFR
      alpha and PDGFR beta are in some cases expressed in neoplastic cells, while the
      stromal counterpart of the same tumor shows the above receptors. Findings on the
      PDGFA/PDGFB expression suggest a receptor-activated status. Our study provides
      new insights into the specific localization of Imatinib mesylate targets in skull
      base chordomas that could be taken into account for the setting up of a
      pharmacological treatment for this tumor.

PMID- 17549376
TI  - Analysis of PIK3CA and Akt/protein kinase B in head and neck squamous cell
      carcinoma.
AB  - PIK3CA, which encodes the catalytic subunit, p110-alpha, of phosphatidylinositol
      3-kinase (PI3K), is implicated in the development and progression of numerous
      neoplasias including head and neck squamous cell carcinoma (HNSCC). In the
      present study, we investigated the occurrence of PIK3CA hot-spot mutations in
      exons 9 and 20, the genomic gain and amplification of PIK3CA, the expression of
      PIK3CA mRNA and the p110 alpha protein, as well as the expression of
      phosphorylated-Akt (pAkt) in 33 cases of HNSCC and compared the results with the
      clinicopathological data. No non-synonymous mutations were detected. PIK3CA copy
      number gain and amplification were found in 36.4 and 9% of the cases,
      respectively, whereas mRNA overexpression was observed in 48.5% of the cases. No
      correlations could be stated between DNA gain, DNA amplification and mRNA
      expression, either between DNA or mRNA status and p110 alpha expression. Direct
      associations were found between PIK3CA gain and lymph node metastases (p=0.025)
      and between mRNA expression and tumour stage (p=0.015). A strong correlation was
      detected between p110 alpha and pAkt expression (p<0.001). Concluding, PIK3CA
      could be an oncogene implicated in HNSCC development. However, our data suggest
      that amplifications or mutations of this gene seldom occur in HNSCC and that
      epigenetic events can play an important role in advanced tumour stages.

PMID- 17549377
TI  - Expression of erbB-1 and erbB-2 genes in normal and pathological human
      endometrium.
AB  - Overexpression of the erbB-1 (EGFR, epidermal growth factor receptor) and erbB-2
      (HER2/neu) proteins contributes to the aggressive behavior of malignant tumors
      originating from the endometrium. We currently examined whether the trend of
      these proteins to overexpression is a direct effect of their gene transcriptional
      activities. Expression of the erbB-1/erbB-2 genes was measured applying the
      quantitative RT-PCR technique in 25 uterine carcinomas, 12 normal endometria, a
      carcinosarcoma and a case of botryoid sarcoma of the uterine cervix. We showed
      that erbB-1 mRNA was overexpressed in 48% (12/25) and erbB-2 mRNA was
      overexpressed in 8% (2/25) of the analysed tumors. The level of expression
      appeared to be significantly higher in the malignant tumors as compared to the
      benign ones for erbB-1 and for erbB-2 (p=0.0001 and p=0.008, respectively). A
      significant correlation between erbB-1 overexpression and tumor differentiation
      was found (Spearman rank correlation test, p<0.001). Concomitant erbB-1 and erbB
      2 overexpression was detected only in 1 out of 25 (4%) uterine neoplasms. erbB-1
      was overexpressed in a sarcoma botryoides of the uterine cervix. Our data suggest
      that erbB-1/erbB-2 overexpression is a direct effect of higher than normal
      transcriptional activity of the encoding genes in a subset of human endometrial
      carcinomas.

PMID- 17549378
TI  - Abrogation of the p16-retinoblastoma-cyclin D1 pathway in head and neck squamous
      cell carcinomas.
AB  - In the present study, we analyzed p16, retinoblastoma (Rb), and cyclin D1
      abnormalities in head and neck squamous cell carcinoma (HNSCC) tissues and cell
      lines from Korean patients. We found a 40% loss of heterozygosity at the D9S171
      locus (9p21 region) these tissues. All eight of the HNSCC cell lines did not
      express the p16 protein, and in two of these cell lines (Amc-HN-6 and 8), this
      was due to a deletion of the p16 gene. Three of the cell lines (Amc-HN-3 to 5)
      that expressed the p16 mRNA had the same nonsense mutation at codon 50 (CGA-Arg
      to TGA-Ter). The Amc-HN-1 and Amc-HN-7 cell lines, which did not express the p16
      mRNA, had a missense mutation at codon 9 (GCC-Ala to GTC-Val) and a silent
      mutation at codon 106 (CCC-Pro to CCA), respectively. The Amc-HN-2 cell line (p16
      exon-positive/mRNA-negative) had a single base deletion at codon 38 (CGG-Arg to
      CG), which resulted in a frameshift and a consequent stop signal at codon 44. The
      Rb protein was detected in all of the eight cell lines, although it was inactive
      in five of these due to hyperphosphorylation. The inverse relationship between
      p16 and Rb was 62.5% (5/8). Cyclin D1 was overexpressed in all of the eight cell
      lines. Our results suggest that the abrogation of p16, the overexpression of
      cyclin D1, and the consequent inactivation of Rb could be important factors in
      the carcinogenesis of HNSCCs.

PMID- 17549379
TI  - GP7 induces internucleosomal DNA fragmentation independent of caspase activation
      and DNA fragmentation factor in NB4 cells.
AB  - DNA fragmentation into internucleosomal fragments is the best recognized
      biochemical event of apoptosis. Two major caspase pathways have been identified
      in the signal transduction leading to DNA fragmentation: the receptor pathway and
      the mitochondrial pathway. DNA fragmentation factor (DFF) has been identified as
      a major apoptotic endonuclease in the internucleosomal DNA fragmentation process.
      However, the potential roles of caspases and DFF in internucleosomal DNA
      fragmentation induced by specific stimuli still need to be investigated since
      caspase-independent pathways and nuclease(s) other than DFF also play important
      roles during this process. In the present study, we investigated the activity of
      GP7 (4-[4"-(2",2",6",6"-tetramethyl-l"-piperidinyloxy) amino]-4'-demethyl
      epipodophyllotoxin), a new spin-labeled derivative of podophyllotoxin semi
      synthesized by our university, to induce apoptosis of the human leukemia cell
      line NB4. GP7 induced the release of cytochrome-c from mitochondria, activations
      of caspase-3, -8, and -9, cleavage of DFF45/inhibitor of caspase-activated DNase,
      activation of DFF40/caspase-activated DNase, and apoptotic DNA fragmentation in
      NB4 cells. The broad-spectrum caspase inhibitor zVAD-fmk abrogated GP7-induced
      caspase-3, -8, and -9 activations but could not inhibit GP7-induced apoptotic DNA
      fragmentation in NB4 cells. Our findings suggest that GP7-induced apoptotic DNA
      fragmentation in NB4 cells is independent of caspase activation and DFF, although
      they are closely involved in this process.

PMID- 17549380
TI  - Anti-tumor effects of immunotherapeutic peptide on the treatment of
      hepatocellular carcinoma with HBc carrier.
AB  - Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death. Tumor
      specific cellular and humoral immunotherapy may be a viable approach for the
      treatment of HCC. This study investigated specific inhibitory and cytotoxic
      effects on hepatocellular carcinoma (HCC) induced by the peptide, designated HBc
      Delta-5L, using HBc carrier with multiple T cell and B cell sequence insertions.
      We developed the HBc Delta carrier containing insertions of multiple CTL and T
      helper (Th) epitopes, which were selected from HCC tumor associated antigens
      (TAAs) including alpha fetoprotein (AFP), melanoma antigen gene (MAGE) and
      telomerase reverse transcriptase (TERT) antigen, and ligands for EGFR and IGFR,
      designated HBc Delta-5L. LDH release assay and IFN-gamma ELISPOT assay were
      carried to determine whether HBc Delta-5L could induce specific cytotoxicity in
      peripheral blood mononuclear cells (PBMC) of HCC donors. The levels of antibodies
      and inhibitory effects of sera of immunized mice against HBc Delta-5L were also
      identified. LDH release assay revealed that PBMC from HCC donor group (n=8)
      stimulated with HBc Delta-5L could specifically kill target tumor cells and
      specific lysis was 62.7% (E:T=60:1). ELISPOT assay showed a significant increase
      in secretion of IFN-gamma from PBMC of HCC donor group in response to HBc Delta
      5L. Further, high specific antibody titers were elicited in immunized mice and
      revealed 42% inhibition of cell growth. These results indicated that inhibitory
      and cytotoxic effects could be efficiently induced by HBc Delta-5L recombinant
      particles using HBc Delta as carrier and suggested that it could be important in
      design of immunotherapeutic approaches.

PMID- 17549381
TI  - Mechanisms of action of FdUMP[10]: metabolite activation and thymidylate synthase
      inhibition.
AB  - FdUMP[10] is a multimer of FdUMP, a suicide inhibitor of thymidylate synthase
      (TS), and was designed to bypass resistance to 5-fluorouracil (5FU). The aim of
      the study was to compare the effect of FdUMP[10] with 5FU and 5-fluoro-2
      deoxyuridine (FUdR) in their efficacy to inhibit their target TS in resistant
      cells. Therefore cell lines FM3A/0, FM3A/TK- (deficient in thymidine kinase) and
      FM3A/TS- (deficient in thymidylate synthase) were used to determine TK dependency
      and specificity for TS inhibition. FdUMP[10] inhibited cell growth with greater
      potency than 5FU and FdUMP. Direct folate-based inhibitors Raltitrexed, GW1843U89
      and Pemetrexed were also evaluated using these cell lines. In TK-deficient cells
      these folate-based inhibitors had greater potency than the fluoropyrimidines
      (FPs). Surprisingly, Pemetrexed even inhibited cell growth in TS-deficient cells.
      Incubation with nucleotidase and phosphatase inhibitors resulted in a reduction
      of cytotoxicity of FdUMP[10], indicating that the drug can be degraded outside
      the cells. In the TS in situ inhibition assay (TSIA) 24 h exposure of FM3A cells
      to 0.5 microM FdUMP and 0.05 microM FdUMP[10] decreased TSIA to 7 and 1% of
      control. Inhibition of nucleotidase and phosphatase activities reduced the effect
      of FdUMP[10], while the inhibitory effect was lower in cells lacking TK.
      FdUMP[10] can enter the cells intact, but also to some extent after
      dephosphorylation. In conclusion, FdUMP[10] can bypass resistance to FUdR by
      direct inhibition of TS.

PMID- 17549382
TI  - An update of the mechanisms of resistance to EGFR-tyrosine kinase inhibitors in
      breast cancer: Gefitinib (Iressa) -induced changes in the expression and nucleo
      cytoplasmic trafficking of HER-ligands (Review).
AB  - Intrinsic resistance to the epidermal growth factor receptor (EGFR; HER1)
      tyrosine kinase inhibitor (TKI) gefitinib, and more generally to EGFR TKIs, is a
      common phenomenon in breast cancer. The availability of molecular criteria for
      predicting sensitivity to EGFR-TKIs is, therefore, the most relevant issue for
      their correct use and for planning future research. Though it appears that in non
      small-cell lung cancer (NSCLC) response to gefitinib is directly related to the
      occurrence of specific mutations in the EGFR TK domain, breast cancer patients
      cannot be selected for treatment with gefitinib on the same basis as such EGFR
      mutations have been reported neither in primary breast carcinomas nor in several
      breast cancer cell lines. Alternatively, there is a general agreement on the
      hypothesis that the occurrence of molecular alterations that activate
      transduction pathways downstream of EGFR (i.e., MEK1/MEK2 right curved arrow
      ERK1/2 MAPK and PI-3'K right curved arrow AKT growth/survival signaling cascades)
      significantly affect the response to EGFR TKIs in breast carcinomas. However,
      there are no studies so far addressing a role of EGF-related ligands as intrinsic
      breast cancer cell modulators of EGFR TKI efficacy. We recently monitored gene
      expression profiles and sub-cellular localization of HER-1/-2/-3/-4 related
      ligands (i.e., EGF, amphiregulin, transforming growth factor-alpha, beta
      cellulin, epiregulin and neuregulins) prior to and after gefitinib treatment in a
      panel of human breast cancer cell lines. First, gefitinib-induced changes in the
      endogenous levels of EGF-related ligands correlated with the natural degree of
      breast cancer cell sensitivity to gefitinib. While breast cancer cells
      intrinsically resistant to gefitinib (IC50 > or =15 microM) markedly up-regulated
      (up to 600 times) the expression of genes codifying for HER-specific ligands, a
      significant down-regulation (up to 10(6) times) of HER ligand gene transcription
      was found in breast cancer cells intrinsically sensitive to gefitinib (IC50 < or
      =1 microM). Second, loss of HER1 function differentially regulated the nuclear
      trafficking of HER-related ligands. While gefitinib treatment induced an active
      import and nuclear accumulation of the HER ligand NRG in intrinsically gefitinib
      resistant breast cancer cells, an active export and nuclear loss of NRG was
      observed in intrinsically gefitinib-sensitive breast cancer cells. In summary,
      through in vitro and pharmacodynamic studies we have learned that, besides
      mutations in the HER1 gene, oncogenic changes downstream of HER1 are the key
      players regulating gefitinib efficacy in breast cancer cells. It now appears that
      pharmacological inhibition of HER1 function also leads to striking changes in
      both the gene expression and the nucleo-cytoplasmic trafficking of HER-specific
      ligands, and that this response correlates with the intrinsic degree of breast
      cancer sensitivity to the EGFR TKI gefitinib. The relevance of this previously
      unrecognized intracrine feedback to gefitinib warrants further studies as cancer
      cells could bypass the antiproliferative effects of HER1-targeted therapeutics
      without a need for the overexpression and/or activation of other HER family
      members and/or the activation of HER-driven downstream signaling cascades.

PMID- 17549383
TI  - PAI-1 induces cell detachment, downregulates nucleophosmin (B23) and fortilin
      (TCTP) in LnCAP prostate cancer cells.
AB  - Plasminogen activator inhibitor (PAI-1) is an anticancer agent that inhibits
      plasmin driven proteolysis, limiting angiogenesis and metastasis. In low
      concentrations it could induce cancer cell motility by interacting with urokinase
      (uPA), its receptor (uPAR), vitronectin and integrins. Active PAI-1 binds to uPA
      forming a complex with uPAR, while the latent form of PAI-1 does not. PAI-1 is
      found in both forms in the circulation. It is not clear which form acts as an
      anticancer agent and how it interacts with malignant cells. To investigate how
      these forms reduce angiogenesis or metastasis, we have created PAI-1 cysteine
      mutants in the active conformation (VLHL PAI-1) with an extended half-life that
      reaches approximately 700 h and its R369A mutant, which has an active
      conformation but cannot bind to uPA (VLHLNS PAI-1). Both VLHL PAI-1s convert into
      the latent form when treated with a reducing agent (DTT) that breaks disulfide
      bridges. Unexpectedly, during routine investigation of LnCAP cell proliferation,
      we have found that cells detach from the culture vessels regardless of PAI-1
      conformation or activity. Further investigation showed that treatment of cancer
      cells with VLHL PAI-1 downregulated nucleophosmin, while all forms of PAI-1
      downregulated fortilin. These two proteins are implicated in important cellular
      processes (cell growth, cell cycle, malignant transformation). This suggests that
      PAI-1, in addition to its well-known anticancer properties, plays an important
      role in cell signaling. We hope that by exploring PAI-1's structure and function
      we might be able to understand and separate the different effects of PAI-1 on
      cancer cells and develop more effective therapeutic strategies in cancer
      treatment.

PMID- 17549384
TI  - Reduced expression of TLR4 is associated with the metastatic status of human
      colorectal cancer.
AB  - Signaling mediating colorectal cancer (CRC) progression is incompletely
      understood. Previously, we identified lipopolysaccharide (LPS), an endotoxin of
      ubiquitously existing colonic bacteria, as a pivotal stimulus increasing the
      metastatic potential of human CRC. Since the ubiquitous colonic bacteria release
      large amounts of LPS this observation could be of enormous relevance for the
      progression of CRC. In this study we present data contributing to the elucidation
      of its mode of action. Since both receptors CD14 and TLR4 act as LPS mediators,
      we determined their expression in various CRC cell lines and in 115 non
      metastatic, lymphogenous-metastatic and haematogenous-metastatic CRC specimens.
      Here we showed that CD14 was not expressed in normal colon epithelium, in non
      metastatic and metastatic CRC. Furthermore, we showed that diverse CRC cell lines
      did not express CD14 under normal conditions and after LPS stimulation. Thus,
      CD14 can be ruled out as a mediator of LPS-induced signaling related to CRC
      progression. In contrast, we found that normal colon epithelium and CRC cell
      lines were positive for TLR4. Furthermore, both lymphogenous and haematogenous
      metastatic cases showed either loss of expression or strong downregulation of
      TLR4 as compared to normal tissue and to non-metastatic tumors. We found that LPS
      stimulation resulted in significant TLR4 upregulation in cells expressing lower
      constitutive TLR4 levels such as CaCo2, whereas no significant response to LPS
      was observed in cells characterized by relatively high amounts of constitutive
      TLR4. Our data suggest that TLR4 expression may be associated with mechanisms
      preventing CRC progression.

PMID- 17549385
TI  - Ultrastructural demonstration of hepatitis B virus production in a mouse model
      produced by hydrodynamic transfection.
AB  - A mouse model of hepatitis B virus (HBV) infection produced by hydrodynamic
      injection of HBV DNA has been recently established. However, the ultrastructural
      demonstration of HBV particles in this mouse model has not as yet been reported.
      In our study, plasmid DNA containing wild-type HBV DNA was rapidly injected into
      8-week-old female SCID mice via the tail vein. Serum levels of HBsAg were
      measured by ELISA kit. Intrahepatic HBV protein expression was detected by
      immunohistochemistry of HBcAg. Ultrastructural study of the serum samples was
      performed by transmission electron microscopy and immunogold electron microscopy.
      Serum HBsAg and intrahepatic HBcAg were detected in HBV DNA-injected mice for at
      least 14 days. Spherical and filamentous particles 22 nm in diameter and double
      shelled Dane-like particles 42 nm in diameter were detected in the sera of mice.
      The ultrastructural features of these particles were identical to HBV particles
      observed in serum from chronic hepatitis B patients. These particles were
      confirmed to be HBV particles by immunogold electron microscopy. We conclude that
      our present HBV mouse model using hydrodynamic transfection of HBV DNA is
      appropriate for production of HBV virions including Dane particles. This mouse
      model may be useful for screening in vivo the efficacy of antiviral drugs.

PMID- 17549386
TI  - Heat shock proteins play a crucial role in tumor-specific apoptosis by REIC/Dkk
      3.
AB  - We recently showed that overexpression of REIC/Dickkopf-3 (Dkk-3), a tumor
      suppressor gene, induced apoptosis in a tumor cell-specific manner. The aim of
      the present study was to determine the mechanisms underlying the selective
      induction of apoptosis. At first, we found a mouse renal carcinoma cell line,
      RENCA, to be extremely sensitive to an adenovirus carrying REIC/Dkk-3 (Ad-REIC),
      and we showed that activation of c-Jun N-terminal kinase (JNK) was a critical
      step in cell death, i.e. a process similar to that in human prostate and
      testicular cancer observed in our previous studies. Among the proteins
      interfering with the activation of JNK, heat shock protein (Hsp)70/72 was reduced
      in expression in RENCA cells compared with that in NIH3T3 cells. An Hsp70/72
      inducer protected RENCA cells from Ad-REIC-induced apoptosis, while an Hsp70/72
      inhibitor sensitized NIH3T3 cells for apoptosis induction. These results indicate
      that functionally active Hsp70/72 is a key factor in tumor cell-specific
      induction of apoptotic cell death and that analyses of the expression levels of
      Hsp70/72 may be essential in determining the significance of Ad-REIC-based gene
      therapy against human cancer.

PMID- 17549387
TI  - Oral route of mini-proinsulin-expressing Ganoderma lucidum decreases blood
      glucose level in streptozocin-induced diabetic rats.
AB  - Oral administration of insulin to control blood glucose has become a hot area of
      diabetes research. The major issue is to produce enough insulin and prevent
      insulin degradation in the acidic environment of the stomach. We hypothesize that
      the natural structure of the cell wall and the endoplasmic reticulum in Ganoderma
      lucidum should help resist the digestion of insulin produced in these cells,
      making this fungus a feasible production and a new delivery system for oral
      insulin. A new mini-proinsulin gene was constructed and was transformed into G.
      lucidum by the Agrobacterium-mediated method. Driven by a strong promoter of GPD
      isolated from Lentinus edodes, expression of mini-proinsulin reached < or =10.4%
      of total soluble protein, equal to 174 microg/g wet weight, which is sufficient
      for oral route. Oral route of transgenic G. lucidum significantly reduced blood
      glucose in streptozocin-induced diabetic rats, as compared to rats fed with
      saline (P<0.0002) or non-transgenic G. lucidum (P<0.0002). Blood glucose was
      reduced < or =64% in 80% of diabetic rats. Evaluation of pancreatic pathology
      showed that 54.5% rats in the transgenic group had no pathological changes, as
      compared to 25% in the saline group and 33.3% in the non-transgenic group. Rats
      in transgenic group had insulitis score <2, while 30% of rats in the saline group
      had insulitis score >2. These experimental results indicate that oral route of
      mini-proinsulin-expressing G. lucidum can be used to control blood glucose in
      diabetes and to improve pancreatic cell function.

PMID- 17549388
TI  - Bone morphogenetic protein-2 and -9 regulate the interaction of insulin-like
      growth factor-I with growth plate chondrocytes.
AB  - Insulin-like growth factor-I (IGF-I) is thought to play an important role in
      skeletal growth and development through its mitogenic and anabolic effects on
      epiphyseal growth plate chondrocytes. The bone morphogenetic proteins (BMPs) have
      been shown to promote endochondral osteogenesis, and some members of the BMP
      family, including BMP-2 and BMP-9, have anabolic effects on chondrocyte
      metabolism. We tested the hypothesis that BMP-2 and BMP-9 interact with IGF-I to
      modulate growth plate chondrocyte mitotic activity. IGF-I, but neither BMP-2 nor
      BMP-9, stimulated chondrocyte DNA synthesis. However, both BMP-2 and BMP-9
      augmented the mitogenic action of IGF-I. BMP-2, but not BMP-9 increased IGF-I
      binding to growth plate chondrocytes in kinetic studies. In affinity labeling
      studies, 125I-IGF-I predominantly labeled an Mr approximately 135-kDa moiety,
      consistent with the alpha subunit of the type 1 IGF receptor and an Mr
      approximately 250-kDa moiety consistent with the type 2 IGF receptor. 125I-IGF-I
      labeling also appeared at Mr approximately 43 kDa, consistent with 125I-IGF-I
      binding to insulin-like growth binding protein-3. Treatment of chondrocytes with
      BMP-2, but not with BMP-9, increased the intensity of the Mr approximately 135
      kDa band and decreased the intensity of the Mr approximately 43-kDa band. Taken
      together, these data suggest that the BMPs may modulate the action of IGF-I via
      the type 1 IGF receptor and/or IGF binding proteins.

PMID- 17549389
TI  - Diallyl disulfide accelerates adipogenesis in 3T3-L1 cells.
AB  - Adipocyte differentiation is regulated by the sequential activation of
      transcription factors such as the CAAT/enhancer binding protein and peroxisome
      proliferator- activated receptor-gamma (PPAR-gamma). Several recent studies have
      shown that regulators of chromatin structure are also involved in adipocyte
      differentiation. Here we investigated the effects of diallyl disulfide (DADS), an
      oil-soluble sulfur compound found in processed garlic and an inhibitor of histone
      deacetylase (HDAC), on adipogenesis. Treatment with DADS accelerated terminal
      differentiation of 3T3-L1 cells into adipocytes as evidenced by Oil red O
      staining and cellular triglyceride assay results. Notably, the inhibition of HDAC
      during the first 2 days was sufficient to stimulate adipogenesis. Western blot
      analysis revealed that DADS increased the level of acetylated histones H3 and H4.
      In addition, DADS increased the expression of adipogenesis-related genes; LPL,
      FAS, SREBP1c, aP2 and PPAR-gamma, and decreased the expression of pref-1, a
      preadipocyte marker gene. Taken together, our results suggest that DADS affects
      adipocyte differentiation through histone acetylation at an early phase of
      adipocyte differentiation.

PMID- 17549390
TI  - DNA methyltransferase expression and DNA methylation in human hepatocellular
      carcinoma and their clinicopathological correlation.
AB  - Aberrant DNA methylation on CpG islands is one of the most consistent epigenetic
      changes in human cancers, and the methylation process is catalyzed by DNA
      methyltransferase (DNMT). We evaluated i) the mRNA levels of three DNMTs; DNMT1,
      DNMT3a and DNMT3b, in 25 hepatocellular carcinomas (HCCs), in their corresponding
      non-cancerous liver tissues and in 7 normal livers by using real-time reverse
      transcriptase-polymerase chain reaction; ii) nuclear expression of DNMT1 and
      DNMT3a proteins in the HCCs by immunohistochemistry, iii) the methylation status
      of 5 genes; p16, p15, E-cadherin, HIC-1 and RASSF1A in the same tissues, and iv)
      the relationships between the above results and the clinicopathological
      characteristics, including prognosis. The differences in mRNA expression levels
      for DNMT1, DNMT3a and DNMT3b were statistically significant between HCC and
      normal livers (p<0.001), HCC and chronic hepatitis (p<0.001) and HCC and
      cirrhosis (p<0.001). An increase in mRNA expression levels of >4-fold for DNMT3b
      in HCCs was significantly associated with a poorer overall survival (p=0.027) and
      shorter metastasis-free survival (p=0.0299). A poorer recurrence-free survival
      was noted in HCCs with a >4-fold increase in DNMT3a mRNA (p=0.0120). The average
      numbers of methylated genes were 0, 1.27, 1.38 and 2.72 for normal livers,
      chronic hepatitis, cirrhosis and HCCs, respectively, and this progressive
      increase from normal livers to chronic hepatitis/cirrhosis through HCC may
      suggest that tumor suppressor gene methylation is an early event in
      hepatocarcinogenesis. These results first suggest that hepatocarcinogenesis
      involves an increased expression of DNMT1, DNMT3a and DNMT3b mRNA and a
      progressive increase in the number of methylated genes from normal liver, chronic
      hepatitis/cirrhosis to HCC and secondly that an increase in the DNMT3a and DNMT3b
      mRNA levels in HCCs relative to their non-cancerous tissues may be a predictor of
      poor survival.

PMID- 17549391
TI  - A novel autosomal partially dominant mutation designated G476D in the keratin 5
      gene causing epidermolysis bullosa simplex Weber-Cockayne type: a family study
      with a genetic twist.
AB  - Epidermolysis bullosa simplex Weber-Cockayne type (EBS-WC) is a genetically
      inherited skin disease characterized by blistering restricted to the palms and
      soles. Its inheritance in nearly all kindreds is caused by a dominant-negative
      mutation in either KRT5 or KRT14, the genes encoding keratin 5 and keratin 14
      proteins, respectively. Rarely, recessive mutations have also been found. We
      described a family with EBS-WC caused by a novel autosomal dominant mutation
      (G476D) in the keratin 5 gene. One family member was first seen with mucosal
      erosions and generalized blisters localized on the anogenital area, trunk, face
      and sites of mechanical trauma. Molecular analysis in this patient showed the
      presence of an additional mutation, an autosomal recessive (G183E) one, in the
      same gene. This observation suggests an additional effect of a recessively
      inherited mutation modulating the phenotypic expression of EBS caused by a
      partially dominant mutation and is important for accurate genetic counseling.

PMID- 17549392
TI  - Overexpression of RGPR-p117 induces the decrease in protein and DNA contents in
      cloned normal rat kidney proximal tubular epithelial NRK52E cells.
AB  - A novel protein RGPR-p117 was discovered as a regucalcin gene promoter region
      related protein that binds to the TTGGC motif. Regucalcin is known to regulate
      the intracellular signaling system in many cell types. RGPR-p117 has been shown
      to enhance the promoter activity of the regucalcin gene in cloned normal rat
      kidney proximal tubular epithelial NRK52E cells. The role of RGPR-p117 in cell
      function remains to be elucidated, however. This study was undertaken to
      determine whether overexpression of RGPR-p117 has an effect on cell
      proliferation, protein and DNA contents in NRK52E cells. NRK52E cells (wild-type)
      or stable RGPR-p117/phCMV2-transfected cells (transfectants) were cultured in
      Dulbecco's minimum essential medium containing 5% bovine serum (BS). RGPR-p117
      was markedly expressed in the transfectants. NRK52E cells (wild-type) or
      transfectants were cultured for 24, 48, or 72 h in a medium containing 5% BS, and
      after subconfluency the cells were cultured for 24, 48, or 72 h in a medium
      without BS. Cell proliferation was not significantly changed in the transfectants
      as compared with that of wild-type cells. Protein and DNA contents in NRK52E
      cells were significantly decreased in the transfectants with cell proliferation
      in the presence of BS. When NRK52E cells with subconfluency were cultured for 24,
      48, or 72 h in a medium without BS, the number of transfectant cells was not
      significantly changed compared with that of wild-type cells. Protein and DNA
      contents in NRK52E cells were significantly decreased in the transfectants
      cultured in a medium without BS after subconfluency. This study demonstrates that
      overexpression of RGPR-p117 induces the decrease in protein and DNA contents in
      NK52E cells, indicating its role in the regulation of cell function.

PMID- 17549393
TI  - A novel IRF6 nonsense mutation (Y67X) in a German family with Van der Woude
      syndrome.
AB  - Van der Woude syndrome (VWS) is the most common type of syndromic orofacial
      cleft, which accounts for approximately 2% of all cleft lip and palate cases. It
      is characterised by variable association of lower lip pits, cleft lip and cleft
      palate, and hypodontia. VWS arises as the result of mutations in the gene
      encoding interferon regulatory factor 6 (IRF6). The disorder is transmitted in an
      autosomal dominant manner, with high penetrance and variable expressivity. Very
      recently, mutations of the IRF6 gene in exons 2-9 have been found in VWS
      patients, suggesting that this gene plays an important role in orofacial
      development. We report a novel mutation of the IRF6 gene in a German family. Five
      out of the 12 persons affected were able to be investigated. The mutation
      produced a stop codon within exon 4 of the IRF6 gene. All 5 patients were
      heterozygous for a base substitution c.201C>A changing the tyrosine codon at
      amino acid position 67 into a stop codon (p.Y67X) in exon 4. The premature stop
      codon was responsible for a truncated protein lacking parts of the DNA- binding
      domain and the complete Smad-interferon regulatory factor-binding domain probably
      essential for interactions with the Smad transcription factors.

PMID- 17549394
TI  - IGF-I enhances cortisol secretion from guinea-pig adrenal gland: in vivo and in
      vitro study.
AB  - Insulin-like growth factor (IGF)-I is a ubiquitously synthesized peptide that,
      along with IGF-II, acts via the IGF-R type I receptor. IGF-I and its receptor are
      expressed in the adrenal gland of humans and bovines, the secretion of which they
      seem to stimulate. As in humans and cows, the main glucocorticoid hormone
      secreted by guinea-pig adrenals is cortisol, and hence we have studied the
      adrenocortical effects of IGF-I in this species. In vivo experiments showed that
      prolonged IGF-I administration raised the plasma concentration of cortisol in
      both normal and dexamethasone/captopril-treated guinea pigs, thereby ruling out
      the possibility that IGF-I may act by activating the hypothalamic-pituitary
      adrenal axis and the renin-angiotensin system. In vitro experiments demonstrated
      that IGF-I enhanced basal, but not maximally agonist [ACTH and angiotensin-II
      (Ang-II)]-stimulated, cortisol secretion from freshly dispersed guinea-pig inner
      adrenocortical cells. The IGF-I immuno-neutralization suppressed the IGF-I
      secretagogue effect, without altering the cortisol response to both ACTH and Ang
      II. IGF-I raised cyclic-AMP and inositol triphosphate release from dispersed
      guinea-pig cells, and the effect was reversed by the adenylate cyclase inhibitor
      SQ-22536 and the phospholipase-C (PLC) inhibitor U-73122. SQ-22536, U-73122, the
      protein kinase (PK) A inhibitor H-89 and the PKC inhibitor calphostin-C decreased
      by approximately 50% the cortisol response of dispersed cells to IGF-I, and the
      combined exposure to SQ-22536 and U-73122 abolished it. We conclude that IGF-I
      stimulates glucocorticoid secretion from guinea-pig adrenocortical cells, acting
      via selective receptors coupled to both the adenylate cyclase/PKA- and PLC/PKC
      dependent signaling cascades.

PMID- 17549395
TI  - Novel effect of estrogen on RANK and c-fms expression in RAW 264.7 cells.
AB  - Temporomandibular disorder (TMD), a progressive disease entity, and
      osteoarthrosis preferentially affect females, denoting a possible role of
      estrogen. Using RAW 264.7 cells, the expression of estrogen receptors (ERs) alpha
      and beta and the consequent effect of estrogen was investigated. We present the
      novel detection of ER beta expression in RAW 264.7 cells. Furthermore, we
      innovatively demonstrated the increase in expression of both ER alpha and beta,
      as well as RANK and c-fms, with estrogen treatment. However, a decrease in
      expression of c-fms, RANK and ER beta, and nearly no change in the expression of
      ER alpha were experienced upon further increase in estrogen concentrations. These
      findings lead us to hypothesize a new mechanism of inflammation in TMD.

PMID- 17549396
TI  - Bone metastasis in prostate cancer: molecular and cellular mechanisms (Review).
AB  - Prostate cancer is the most common cancer in men in Western countries, with a
      high incidence of bone metastasis. The bony metastasis is incurable and
      contributes significantly to disease-specific morbidity and mortality. The
      molecular and cellular mechanisms leading to the development of bone metastasis
      in prostate cancer remain unclear, but are currently under intensive
      investigation. In this review, we summarized the current understanding of bone
      metastasis in prostate cancer. The rapid progress in the genetic predisposition
      that makes prostate cancer cells more prone to spread to bone, bone-derived
      factors which are involved in the development of bone metastasis at the level of
      the local microenvironment, the interactions between metastatic prostate cancer
      cells and bone marrow endothelial cells, osteoblasts, and osteoclasts, are
      discussed in this article.

PMID- 17549397
TI  - Non-receptor protein-tyrosine kinases as molecular targets for antiangiogenic
      therapy (Review).
AB  - Antiangiogenic therapy, including blockade of vascular endothelial growth factor
      (VEGF) signaling, was highly anticipated to improve the prognosis for patients
      with advanced cancers following the success of preclinical animal models.
      However, antiangiogenic monotherapy with VEGF antagonists has produced
      disappointing results in clinical trials to date. One of the reasons for this
      poor outcome is that angiogenesis is not solely regulated by VEGF. Inhibition of
      VEGF signaling, therefore, may select for tumor cell populations that stimulate
      angiogenesis through VEGF-independent pathways. Successful antiangiogenic
      therapy, therefore, may require simultaneous blockade of signaling downstream
      from multiple proangiogenic factor receptors. Recently, we found that non
      receptor protein-tyrosine kinases, including members of the Src and Fes families,
      play vital roles in the responses of cultured endothelial cells to several
      proangiogenic factors. In this review, we summarize the contributions of these
      kinase families to angiogenic pathways in endothelial cells, and discuss the
      potential of these kinases as new targets for antiangiogenic drug discovery.

PMID- 17549398
TI  - Induction of G1 arrest and apoptosis by Scutellaria barbata in the human
      promyelocytic leukemia HL-60 cell line.
AB  - Scutellaria barbata has been used to treat cancer in Chinese medicine. The
      responsible anticancer mechanism, however, is not clear. Here we demonstrated an
      inhibitory mechanism due to a Scutellaria barbata extract (SBE) on a human
      promyelocytic leukemia cell line (HL-60) that has a mutation in the tumor
      suppressor gene p53. HL-60 cells were incubated with various concentrations of
      SBE. After a 24-h incubation, cytotoxicity and apoptosis were determined by MTT
      and DNA fragmentation assay, respectively. After treatment with SBE, cell cycle
      arrest was determined by measuring the cell number stained by 5'-bromo-2'
      deoxyuridine (BrdU) and 7-amino-actinomycin D (7-AAD). Treatment of cells with
      SBE resulted in a concentration- and time-dependent inhibition of growth and a G1
      phase arrest of the cell cycle. This effect was associated with a marked decrease
      in the protein expression of cyclin A, D1, D2, D3, and E and their activating
      partners, cyclin-dependent kinases (CDK) 2, 4, and 6 with concomitant
      upregulation of p21, cyclin-dependent kinase inhibitor. Downstream of the CDK
      inhibitory protein-CDK/cyclin cascade, SBE decreased phosphorylation level of
      retinoblastoma protein. SBE treatment also resulted in apoptosis evidenced by an
      increase of sub-G1 phase cells, DNA fragmentation and degradation of the
      inhibitory protein for the caspase-activated deoxyribonuclease. The molecular
      mechanism during SBE-mediated growth inhibition in HL-60 cells may be due to
      modulation of the cell-cycle machinery and the induction of apoptosis.

PMID- 17549399
TI  - GM-CSF up-regulates the expression of CCL2 by T lymphocytes in mammary tumor
      bearing mice.
AB  - MCP-1/CCL2 (monocyte chemoattractant protein-1/CC chemokine ligand 2) is a beta
      or CC chemokine that is expressed by a variety of cell types, including
      fibroblasts, endothelial, smooth muscle, and glial cells. In addition, cells
      involved in immunity, such as monocytes/macrophages, neutrophils, and eosinophils
      have also been shown to express this chemoattractant. Using a murine model of the
      D1-DMBA-3 mammary adenocarcinoma, we demonstrated the unique production of CCL2
      by splenic T lymphocytes from tumor-bearing animals. Because this tumor produces
      GM-CSF, and this factor is also up-regulated in the B lymphocytes of tumor
      bearing mice, we looked at the ability of GM-CSF to induce CCL2 production by T
      cells. Treatment of normal and tumor bearers' T cells with GM-CSF resulted in an
      increased secretion of this chemokine. This up-regulation was seen with or
      without stimulation by Concanavalin A, although these treatments were additive in
      their effects. The induction of CCL2 was studied at the molecular level by
      analyzing the effect(s) of a variety of physiological and pharmacological agents
      on cultured T cells. These results suggest that the tumor-derived factor GM-CSF
      activates various signaling pathways within splenic T cells to up-regulate CCL2
      expression.

PMID- 17549400
TI  - RNA interference-mediated targeting of urokinase plasminogen activator receptor
      and matrix metalloproteinase-9 gene expression in the IOMM-lee malignant
      meningioma cell line inhibits tumor growth, tumor cell invasion and angiogenesis.
AB  - Meningiomas are the most commonly occurring tumors of the central nervous system
      including the brain and spinal cord. Malignant meningiomas are highly aggressive
      and frequently recur after surgical resection of the tumor. Our previous studies
      have reported that urokinase plasminogen activator receptor (uPAR) and matrix
      metalloproteinase-9 (MMP-9) play important roles in tumor progression. In the
      present study, we have attempted to evaluate the roles of these molecules in the
      malignant meningioma tumor microenvironment and to determine the effectiveness of
      using single or bicistronic small interfering RNA constructs for uPAR and MMP-9
      on tumor cell proliferation, migration, invasion, angiogenesis and regression of
      pre-established orthotopic tumors. Transfection of single or bicistronic
      constructs downregulated uPAR and MMP-9 in meningioma cells compared to controls.
      A significant reduction in tumor invasion was determined with matrigel gel and
      spheroid invasion assays in meningioma cells after transfection of these
      plasmids. Furthermore, downregulation of uPAR and MMP-9 reduced migration of
      tumor spheroids on vitronectin-coated plates. uPAR and MMP-9 downregulation
      suppressed capillary network formation, in both in vitro and in vivo models.
      Also, it is well known that tumor cells manipulate intracellular signaling
      pathways to aid in various processes involved in tumor progression. Our study
      revealed that downregulation of uPAR and MMP-9 leads to a decrease in the
      activation of some of the important enzymes participating in the MAPK and PI3
      kinase pathways, which in turn, might decrease cell survival and proliferation.
      In addition, we analyzed the efficiency of RNAi-mediated targeting of uPAR and
      MMP-9 in pre-established tumor growth in vivo. We observed a significant
      regression of pre-established orthotopic tumors upon RNAi-mediated targeting of
      uPAR and MMP-9. In addition, the present study indicated that targeting both the
      proteins simultaneously augmented the therapeutic treatment of human meningiomas.

PMID- 17549401
TI  - Down-regulation of uPAR and uPA activates caspase-mediated apoptosis and inhibits
      the PI3K/AKT pathway.
AB  - Urokinase plasminogen activator (uPA) and its receptor (uPAR) play a major role
      in invasion and proliferation. A growing body of evidence has suggested that the
      uPA system promotes tumor metastasis by several different mechanisms, and not
      just solely by breaking down the ECM. In this study we have used RNAi-mediated
      simultaneous down-regulation of uPAR and uPA to determine the signaling pathway
      molecules and caspase-mediated apoptosis. From our in vitro experiments, we have
      observed that plasmid-based RNAi-mediated down-regulation of uPAR and uPA in
      SNB19 human glioma cells caused a decrease in the levels of uPAR protein and uPA
      enzyme activities. In addition, we observed a decrease in the phosphorylation of
      the Ras-activated pathway molecules such as FAK, p38MAPK, JNK and ERK1/2, as well
      as the MEK-activated phosphatidylinositol 3-kinase (PI3k) pathway, and also
      retarded the dephosphorylation of p-AKTser473 and p-mTORser2448, indicative of a
      feedback signaling mechanism of the uPAR-uPA system. Activation of caspase 8
      accompanied by the release of cytochrome c and cleavage of PARP was also observed
      and indicative of Fas-mediated apoptosis. The use of FMK-VAD-FAK peptides coupled
      with FITC indicated activation of polycaspases, which was accompanied by the
      presence of fragmented nuclei. Our studies provide evidence for the presence of a
      feedback response of the uPAR-uPA system indicative of the multifaceted role of
      uPAR, and also the therapeutic potential of simultaneously targeting uPAR and uPA
      in cancer patients.

PMID- 17549402
TI  - Characterization of novel murine anti-CD20 monoclonal antibodies and their
      comparison to 2B8 and c2B8 (rituximab).
AB  - Rituximab is the first anti-cancer antibody approved by the FDA for the treatment
      of B-cell non-Hodgkin lymphoma (B-NHL), alone or in combination with
      chemotherapeutic drugs. Further, rituximab is now being examined in a variety of
      CD20+ neoplastic diseases as well as B-cell-induced autoimmune diseases. The
      clinical response to rituximab is significant, resulting not only in tumor
      regression but also prolongation of survival. However, a subset of patients does
      not initially respond to rituximab or develops resistance to its further
      treatment. Therefore, alternative therapies for these patients are strongly
      desired. Rituximab activity has been thought to be by antibody-dependent cellular
      cytotoxicity, complement-dependent cytotoxicity and apoptosis, and studies in
      model systems established the role of rituximab in cell signaling-induced
      perturbation of anti-apoptotic survival pathways, suggesting that the patients
      unresponsive to rituximab may be overcome with other CD20 antibodies with
      different activities. This study investigated eight novel murine antibodies
      directed against CD20 for their physical and biological properties in comparison
      with 2B8 and c2B8 (rituximab). These antibodies were derived by various antigenic
      and immunization procedures and selected for CD20 activity. Analysis of these
      antibodies revealed that they all bound to various B-cell lines and CD20
      transfected CHO cells. Six of the eight antibodies shared similar variable-region
      amino acid sequences that were also shared by 2B8 while two monoclonal antibodies
      did not. Of them, 1K1791 has a distinct heavy chain and both 1K1791 and 1K1782
      have distinct light chains. Not all of the antibodies inhibited cell growth and
      only two antibodies reacted with fixed GST-CD20 recombinant fusion protein.
      Noteworthy, 1K1791 was found to inhibit cell proliferation and also induced
      caspase-independent apoptosis in the absence of cross-linker. These findings
      identified new antibodies with properties and epitope specificities different
      from 2B8. The potential clinical application of such antibodies in the treatment
      of B-NHL and rituximab-resistant B-NHL is discussed.

PMID- 17549403
TI  - Insulin-like growth factor-I has different effects on myogenin induction and cell
      cycle progression in human alveolar and embryonal rhabdomyosarcoma cells.
AB  - Alveolar rhabdomyosarcoma (RMS) has a much poorer outcome than embryonal RMS. In
      this study, we found that IGF-I affected the induction of myogenin and cell cycle
      progression in alveolar RMS cells, but not in embryonal RMS cells. IGF-I enhanced
      the induction of myogenin protein in alveolar RMS SJ-Rh30 and KP-RMS-MS cells as
      it did in myoblast C2C12 cells, but not in embryonal RMS RD or KP-RMS-KH cells.
      IGF-I induction of myogenin protein was blocked by anti-IGF-IR monoclonal
      antibody alphaIR-3 and the mTOR-specific inhibitor rapamycin. In Rh30mTOR-rr
      cells, which stably express a rapamycin-resistant mutant mTOR, rapamycin did not
      inhibit IGF-I induction of myogenin protein. These data suggest that IGF-I
      induces myogenin in alveolar RMS cells through the IGF-IR/mTOR pathway. In C2C12
      cells, IGF-I induces myogenin protein followed by cell cycle arrest leading to
      myogenic differentiation. IGF-I promoted G1-S cell cycle progression without any
      signs of terminal differentiation in alveolar RMS cells. On the other hand, IGF-I
      promoted neither cell cycle arrest nor G1-S cell cycle progression in embryonal
      RMS cells. In alveolar RMS SJ-Rh30 cells, 4E-BP1, one of two effectors downstream
      of mTOR, was continuously hyperphosphorylated by IGF-I, whereas in embryonal RMS
      RD cells, 4E-BP1 was only transiently hyperphosphorylated. These findings suggest
      that the different effects of IGF-I on myogenin induction and cell cycle
      progression in alveolar and embryonal RMS cells are due to a difference of
      phosphorylation status of 4E-BP1. These different responses to IGF-I help to
      explain immunohistochemical and clinical behavioral differences between alveolar
      and embryonal RMS.

PMID- 17549404
TI  - Overexpression of c-Met and of the transducers PI3K, FAK and JAK in breast
      carcinomas correlates with shorter survival and neoangiogenesis.
AB  - c-Met is responsible for cell motility and tumour spreading. c-Met expression and
      signal transducers reflecting c-Met functionality were investigated in breast
      carcinomas, in correlation with patient outcome and tumour vasculature. Tissue
      microarrays of 930 breast carcinomas were constructed, categorised according to
      patients' follow-up (4- to 10-year follow-up; median, 6.5 years). Standardised
      immunocytochemical procedures were performed using anti-c-Met, -PI3K, -FAK, -JAK,
      and -CD146, -FYN and an automated autostainer (Ventana). High-throughput
      densitometry measuring the extent of immunoprecipitates was assessed by image
      analysis (SAMBA). c-Met overexpression correlated with poor survival along with
      PI3K and FAK reflecting c-Met functionality and CD146 and FYN expression in
      endothelial cells. Automated quantification of immunocytochemical precipitates
      using image analysis was shown to provide an objective means of measuring
      cellular proteins that are potentially relevant for current practice in
      pathological diagnosis and for specific therapy combining inhibitors of both c
      Met and downstream transducer pathways, and of tumour angiogenesis.

PMID- 17549405
TI  - Molecular characterization of the desmoplastic tumor stroma in medullary thyroid
      carcinoma.
AB  - Medullary thyroid carcinomas are aggressive neoplasias that metastasize very
      early to loco-regional lymph nodes, and tumors with a desmoplastic stromal
      reaction have a higher incidence of lymph node metastasis. In order to
      characterize the desmoplastic response in thyroid cancers, we evaluated the
      expression pattern of three molecular markers of activated
      fibroblasts/myofibroblasts, namely, fibroblast activation protein alpha
      (FAPalpha), tenascin-C (Tn-C), and alpha-smooth muscle actin (alpha-SMA), as well
      as the endothelial markers endoglyx-1, CD34 and CD31 in a series of 28 metastatic
      and non-metastatic medullary thyroid cancers. Immunohistochemical studies
      demonstrated that the three fibroblast activation markers (FAPalpha, Tn-C, alpha
      SMA) are consistently expressed in the peritumoral and intratumoral stromal
      compartment of medullary thyroid carcinomas and expression of FAPalpha and Tn-C
      correlated with the degree of desmoplasia determined histologically (p=0.001 for
      FAPalpha and p<0.001 for Tn-C). Moreover, the extent of desmoplasia as well as
      the expression of FAPalpha and Tn-C correlated with the presence of lymph node
      (LN) metastases (p=0.002, p=0.005 and p=0.002, respectively). No correlation was
      found between the microvessel density (neoangiogenesis) in the tumor stroma,
      assessed with the endoglyx-1, CD34 and CD31 markers, and the degree of
      desmoplasia or incidence of LN metastases. Using a bioinformatics-based search of
      the BioExpresstrade mark database we found in a series of 48 thyroid cancers a
      significant correlation between FAPalpha RNA expression and incidence of LN
      metastases also in papillary cancers. These findings suggest that the link
      between specific molecular markers of tumor stromal reaction and locoregional
      metastasis extends from medullary to other thyroid cancer types.

PMID- 17549406
TI  - Overexpression of VEGF and TGF-beta1 mRNA in Pap smears correlates with
      progression of cervical intraepithelial neoplasia to cancer: implication of YY1
      in cervical tumorigenesis and HPV infection.
AB  - The screening of neo-angiogenesis related gene expression has uncovered many
      disrupted molecular pathways which may significantly confer to malignant
      transformation of various cell types including cervical cells. The objective of
      the present study was to delineate whether changes in certain gene expression
      profiles during the malignant conversion of the uterine cervix can be potentially
      used to predict the clinical course and outcome of the cervical pathology. Total
      RNA was isolated from Pap smears obtained from healthy females or patients
      diagnosed with low-grade squamous cervical intraepithelial lesions (LG-SIL), high
      grade (HG)-SIL or cervical carcinoma. VEGF, TGF-beta1 and YY1 mRNA expression
      levels were assessed by QRT-PCR. Confirmation of YY1 protein discrepancy among
      cervical tissues of different histopathology was performed by
      immunohistochemistry. All tested genes showed statistically significant
      expression variations among the indicated groups. VEGF and TGF-beta1 mRNA
      overexpression was found to be associated with progression from low-grade to high
      grade cervical intraepithelial neoplasia (CIN), while YY1 showed constitutively
      elevated transcript levels in CIN and cervical cancer compared to controls. At
      the protein level YY1 was also overexpressed in HG-SIL and cancer tissues
      compared to LG-SIL. Both YY1 transcript and protein overexpression were
      associated with HPV18- or HPV16-infected samples. Spearman analysis revealed a co
      expression pattern for VEGF and TGF-beta1 mRNAs in normal cervix and LG-SIL;
      however, YY1 expression correlated negatively with VEGF and TGF-beta1 transcript
      levels upon the onset of the cervical neoplastic transformation. Our findings
      provide for the first time evidence for the implication of YY1 in uterine cervix
      carcinogenesis and suggest that VEGF, TGF-beta1 and YY1 could be useful
      biomarkers of cervical malignant transformation as well as potential targets for
      therapeutic approaches.

PMID- 17549407
TI  - Activation of a system A amino acid transporter, ATA1/SLC38A1, in human
      hepatocellular carcinoma and preneoplastic liver tissues.
AB  - The expression of amino acid transporter (AT) mRNAs including A system
      (ATA1/SNAT1/SLC38A1, ATA2/SNAT2/SLC38A2 and ATA3/SNAT3/SLC38A4), L system
      (LAT1/SLC7A5 and LAT2/SLC7A8), and y+ (CAT2/SLC7A2) genes, were compared among
      hepatocellular carcinoma (HCC) and non-cancerous liver cells. Among them the ATA1
      mRNA expression was significantly elevated in all HCC cell lines (HepG2, HLF,
      HuH7 and JHH4) examined compared with normal liver tissue. We further discovered
      that the expression of ATA1 mRNA was significantly activated in HCC tissues and
      also elevated in pre-malignant cirrhotic livers from HCC patients, compared with
      normal livers from non-HCC patients. The ATA1 protein was extensively accumulated
      in the cytoplasm of pre-malignant liver and most HCCs, while being weak or
      undetectably low in normal liver tissues. SiRNA-mediated suppression of
      endogenous ATA1 lowered the viability of HepG2 cells. Thus, the activation of
      ATA1 confers growth and survival advantages in pre-malignant and malignant liver
      lesions.

PMID- 17549408
TI  - Follow-up of tumor development in the colons of living rats and implications for
      chemoprevention trials: assessment of aspirin-difluoromethylornithine
      combination.
AB  - We aimed to establish a reliable procedure allowing the follow-up of tumor
      development by computed tomographic (CT) colonography in an animal model of colon
      carcinogenesis in order to assess the chemopreventive efficacy of aspirin and
      difluoromethylornithine (DFMO) given in combination. Fischer rats received an
      intraperitoneal injection (25 mg/kg) of dimethylhydrazine (DMH) once a week for
      two weeks in order to initiate colon carcinogenesis. Five months after the last
      injection of DMH, a first CT colonography was performed and rats were then
      randomly separated into two groups (control and experimental). The experimental
      group received a 0.1% mixture of aspirin and DFMO in drinking water. CT
      colonography was performed at 6, 7 and 8 months. Data showed a precise
      correlation between location and size of tumors found at autopsy and those
      detected by CT colonography at 8 months. All tumors were also detected on the CT
      views obtained previously. Animals of the aspirin/DFMO group exhibited an
      inactivation of ornithine decarboxylase, a key enzyme in polyamine biosynthesis,
      and a two-fold reduction in the prostaglandin E2 content of the colonic mucosa
      (p<0.01). In rats with tumors at the start of the aspirin/DFMO treatment, a
      significant slow-down of tumor development was observed. In contrast, in rats
      where no tumors were detected at the start of the treatment, tumor formation was
      inhibited. Our data show that CT colonography represents a reliable method to
      assess in a living animal the efficacy of chemopreventive agents.

PMID- 17549409
TI  - Expression and gene polymorphisms of the chemokine CXCL5 in colorectal cancer
      patients.
AB  - Several studies indicate that chemokines play important roles in colorectal
      mucosal immunity by recruiting leukocytes into and out of the lamina propria
      adjacent to the epithelium. The chemokine CXCL5 which is expressed by epithelial
      cells within colorectal mucosa is a chemoattractant for neutrophils and has been
      implicated in Crohn's disease and ulcerative colitis. In addition, CXCL5 is one
      chemokine which promote angiogenesis related to cancer. The objective of this
      study was to determine by ELISA assay whether CXCL5 protein level is altered in
      colorectal cancer (CRC) tissues (n=80) compared with paired normal mucosa.
      Furthermore, the plasma CXCL5 levels from CRC patients (n=62) compared with
      controls (n=71) were also examined. Using a TaqMan system we screened for -156G-
      > C and +398G-->A CXCL5 gene variants in CRC patients (n=228) and a control group
      (n=231) to assess the role of CXCL5 genotype in CRC. The analyses showed that
      CXCL5 protein level in colorectal tumours was significantly (P<0.0001) higher
      than in normal tissue and was lower in plasma in CRC patients compared with
      controls (P=0.026). Immunohistochemistry revealed CXCL5 immunoreactivity mainly
      in epithelial cells of the colorectal carcinoma and in normal epithelial cells.
      Furthermore, patients who were -156C carriers had higher CXCL5 protein
      concentration compared with -156G carriers in normal tissue (P=0.027) and CXCL5
      protein levels in cancerous tissue tended to be higher for the patient -156C
      carriers (P=0.059). To our knowledge this is the first report on the influence of
      CXCL5 gene variants and their relation to expression of CXCL5 protein in human
      CRC.

PMID- 17549410
TI  - Variability of in situ proteomic profiling and implications for study design in
      colorectal tumors.
AB  - Knowledge of intrinsic tumor heterogeneity is vital for understanding of tumor
      progression mechanisms as well as for providing efficient treatments. In situ
      proteomic profiling of tumors is a powerful technology with potential to enhance
      our understanding of tumor biology, but sources of variability due to patient and
      tumor heterogeneity are poorly understood and are the topic of this
      investigation. Clarification of variability within case and between cases is also
      important for designing future studies. Direct protein profiling by matrix
      assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF
      MS) is a sensitive and powerful technology for obtaining hundreds of protein
      expression peaks from a thin tissue section. By combining robotic microspotting
      and laser capture microdissection with MALDI MS, we acquired multiple spectra per
      case to evaluate inter- and intra-case variability in human colorectal tumor and
      murine cecal carcinoma. We detected 256 peaks from 164 samples of 111 patients,
      which consisted of 55 normal colorectal mucosal samples, 24 adenomas, 71 primary
      carcinomas, and 14 hepatic metastases. In addition, we detected 291
      peptide/protein peaks from 34 orthotopically transplanted murine cecal carcinomas
      and 14 hepatic metastases. In human colorectal samples, we observed that
      proteomic profiling in adenomas was more homogeneous across patients than in
      normal mucosa specimens (p=0.0008), but primary carcinoma exhibited greater
      heterogeneity than normal mucosa and adenomas (both p<0.0001). Murine cecal
      carcinomas were homogeneous within and between carcinomas, while their hepatic
      metastases tended toward greater intra-tumor differences (p<0.0001). Inter- and
      intra-case variability was approximately equal for many protein peaks. Acquiring
      up to 5 subsamples per case could reduce the total number of cases required, but
      further reduction from additional subsampling was modest unless intra-case
      variability comprises a greater proportion of total variation (e.g. >70%). In
      summary, this study characterizes intra- and inter-case variability of high
      throughput protein expression in colorectal tumors, and provides guidance for the
      sample numbers required for in situ proteomic studies.

PMID- 17549411
TI  - Mammary tumor induction in ACI rats exposed to low levels of 17beta-estradiol.
AB  - Animal models play a major role in understanding the etiology, molecular
      mechanisms, strategizing intervention and treatment of human diseases. ACI, an
      inbred line derived from August and Copenhagen strains, is unique for its
      susceptibility to estrogen-induced mammary tumors. Histologically and in many
      molecular aspects, the tumors formed in these rats are similar to human breast
      cancers. Previous studies have shown high mortality and significant weight loss
      in this model associated with pituitary gland abnormality. We hypothesized that
      this could be due to overwhelming the biological system with estrogen. Three
      groups of female ACI rats (7-8 weeks) received either 3-cm sham silastic
      implants, or the conventional 3-cm silastic implants containing 27 mg of 17beta
      estradiol, or 1.2-cm silastic implants containing 9 mg 17beta-estradiol. The sham
      and 3-cm implant rats were euthanized at 180 days while the 1.2-cm implant rats
      were euthanized at 240 days. The 1.2-cm implants resulted in significantly
      reduced serum estrogen levels and pituitary gland size. Animals with 1.2-cm
      implants had 100% tumor incidence, while not all rats developed tumors with 3-cm
      implants. Both the tumor burden (from 1,011+/-402 to 2,324+/-454 mm(3); p=0.01)
      and tumor multiplicity (from 5.78+/-1.4 to 7.6+/-1.04) increased by lowering the
      estrogen dose, and the inter-animal variability in the tumor indices decreased.
      Finally, the weight of the pituitary gland was also significantly (p=0.0004)
      reduced (from 178+/-23.5 mg to 80+/-8.9 mg) and the mortality rate decreased from
      42% to 0% (p=0.01). Our data indicate that the improvised model will provide
      valuable insights into the molecular alterations in the estrogen-induced mammary
      tumorigenesis and will be ideal for inhibition studies.

PMID- 17549412
TI  - Cytogenetic characterisation and proteomic profiling of the Imatinib-resistant
      cell line KCL22-R.
AB  - Approximately 30% of chronic myeloid leukemia patients show initially no response
      to Imatinib, a potent inhibitor of BCR-ABL. This intrinsic resistance may be due
      to BCR-ABL-independent cell growth. Here we analysed the cytogenetic anomalies
      and the proteomic profiling in KCL22-S and KCL22-R, two Imatinib-sensitive and 
      resistant derivative cell lines of KCL22. A tetrasomy 8 and a non-reciprocal
      translocation +der(6)t(6;13)(p11.1;q12) were found only in KCL22-R as new evolved
      anomalies. Chromosome der(6)t(6;13) showed four variants differing in the
      chromatin content of 13q14-13qter including the retinoblastoma gene. Due to these
      sub-clones, approximately 65-79% of the Imatinib-treated KCL22-R cells showed a
      disomy and 21-35% a monosomy for 13q14. Imatinib removal reduced the main clone
      to approximately 20% in the benefit of the monosomic sub-clones. This was
      accompanied by an increased apoptosis rate and was revertible by Imatinib re
      treatment. This effect may be connected with genes located in 13q14-qter.
      Proteomic profiling of the cell lines performed with ProteinChip technology
      (SELDI) revealed several differentially expressed proteins (n=45). In summary, we
      demonstrate here the complex changes on the cytogenetic and proteomic level which
      could be caused by Imatinib and the resistance resulting from it.

PMID- 17549413
TI  - Inhibition of Stat3 activation and tumor growth suppression of non-small cell
      lung cancer by G-quartet oligonucleotides.
AB  - Lung cancer is the leading cause of cancer mortality in the United States.
      Despite advances made over the past decades, the overall survival of patients
      with lung cancer remains dismal. Here we report novel G-quartet
      oligodeoxynucleotides (GQ-ODN) that were designed to selectively target signal
      transducer and activator of transcription 3 (Stat3), in the treatment of human
      non-small cell lung cancer (NSCLC). The objective of this study was to evaluate
      the effects of two novel GQ-ODN STAT3 inhibitors, T40214 and T40231, on NSCLC
      bearing nude mice. NSCLC bearing nude mice were assigned to 5 groups, which were
      treated by vehicle, control ODN, T40214, T40231, and Paclitaxel, respectively.
      Tumors were measured, isolated and analyzed using Western blotting, immuno
      histochemistry, RPA and TUNEL. Results show that GQ-ODN T40214 and T40231
      significantly suppress the growth of NSCLC tumors in nude mice by selectively
      inhibiting the activation of Stat3 and its downstream proteins Bcl-2, Bcl-xL, Mcl
      1, survivin, VEGF, Cyclin D1 and c-myc; thereby, promoting apoptosis and reducing
      angiogenesis and cell proliferation. These findings validate Stat3 as an
      important molecular target for NSCLC therapy and demonstrate the efficacy of GQ
      ODN in inhibiting Stat3 phosphorylation.

PMID- 17549414
TI  - Small interfering RNA against PTTG: a novel therapy for ovarian cancer.
AB  - Ovarian epithelial cancer is a significant cause of death among women, accounting
      for 5% of all female cancer-related fatalities. A lack of reliable detection
      methods and resistance to chemotherapy agents are considerable obstacles in the
      treatment of this cancer. Recently, high-level expression of the pituitary tumor
      transforming gene (PTTG) was found in a wide range of tumors, including ovarian
      cancers. Elevated PTTG levels were found to induce cellular transformation in
      vitro and tumor formation in nude mice. Therefore, we hypothesize a correlation
      exists between the levels of PTTG expression and tumorigenesis, and that down
      regulation of PTTG levels will result in the suppression of tumor growth. We used
      small interfering RNA (siRNA) to silence PTTG expression in human A2780 ovarian
      carcinoma cells and assessed the effect of PTTG silencing in tumor formation in
      vitro and in vivo. The siRNA directed against PTTG reduced its expression at both
      the mRNA and protein levels. A fifty percent reduction in cell proliferation was
      achieved in cells constitutively expressing PTTG siRNA compared to vector or
      control-siRNA transfected cells. Furthermore, colony formation in soft agar was
      reduced by 70% in PTTG siRNA stable cell lines. Using nude mice, we showed that
      animals injected with A2780 cells constitutively expressing PTTG-siRNA decreased
      the incidence of tumor development and tumor growth. Taken together, these
      results strongly suggest that PTTG may serve as an important molecular target for
      the discovery of new anticancer agents and treatment strategies.

PMID- 17549415
TI  - The benzene metabolite hydroquinone enhances G2-chromosomal radiosensitivity by
      inducing a less-efficient G2-M-checkpoint in irradiated lymphocytes.
AB  - The hypothesis tested is that a 24-h pre-irradiation-exposure of peripheral blood
      lymphocytes (PBL) to the benzene metabolite hydroquinone (HQ), at doses that are
      non-acutely toxic (5 microM), induces a less efficient G2-M-checkpoint and
      enhances the G2-chromosomal radiosensitivity in a statistically significant
      manner (p<0.01). A less efficient G2-M-checkpoint may allow the transition of
      damaged cells from G2- to M-phase and experimental data in the present work
      support this hypothesis. In fact HQ sensitizes lymphocytes obtained from healthy
      donors, as they exhibit increased G2-chromosomal radiosensitivity which
      interestingly is similar to that observed in cases of radiosensitive cancer-prone
      individuals. This finding is important since a deficiency in cell cycle
      checkpoints and an increase in G2-chromosomal radiosensitivity are linked to
      chromosomal instability, cancer proneness and the development of leukemia. The
      observed chromosome radiosensitization may be a consequence either of an effect
      of HQ on the initial induction of radiation-induced chromosomal aberrations, or
      on the DNA repair capacity of the cells, or it may be linked to HQ-induced
      alterations in the cell cycle and feedback control mechanism during the G2- to M
      phase transition. In order to elucidate which is the mechanism involved,
      conventional cytogenetics and premature chromosome condensation (PCC)
      methodologies were applied. The experimental data obtained support the hypothesis
      that HQ increases G2-chromosomal radiosensitivity in human peripheral blood
      lymphocytes by inducing a less efficient G2-M-checkpoint, facilitating thus the
      transition of damaged cells from G2- to M-phase.

PMID- 17549416
TI  - Topoisomerase IIalpha mRNA and protein expression vs. in vitro drug resistance
      and clinical outcome in acute leukaemia.
AB  - The objective of this study was to correlate the expression of topoisomerase
      (topo) IIalpha to in vitro drug sensitivity and to the clinical outcome in
      patients with acute leukaemia. Leukaemic cells were isolated from bone marrow or
      blood from 94 patients. Topo IIalpha mRNA (n=58) and protein (n=60) expression
      was determined by real-time RT-PCR and flow cytometry, respectively. In both
      groups, chemosensitivity testing by a bioluminescence ATP assay was performed to
      a variable extent for both topo IIalpha poisons and non-topo IIalpha targeting
      drugs. Topo IIalpha mRNA expression varied with relative values ranging from 0.03
      to 14.20 (median 1.10). The median value for topo IIalpha protein-positive cells
      was 23% (range 0-99%). Cell samples from patients with a high (>median value)
      percentage of topo IIalpha-positive cells were significantly more sensitive to
      the topo IIalpha active drugs etoposide and daunorubicin, and showed a borderline
      value for idarubicin (p=0.08), while there was no difference for non-topo IIalpha
      targeting drugs. However, we did not find any significant differences in mRNA
      expression or the percentage of topo IIalpha-positive cells in patients who
      achieved complete remission after at most two induction courses compared with
      those who did not, nor did we find any difference in survival when patients with
      high mRNA expression/percentage of topo IIalpha-positive cells were compared with
      patients with low values. We conclude that expression of topo IIalpha, determined
      as percentage of topo IIalpha-positive cells, in leukaemic cells correlates to
      chemosensitivity in vitro against topoisomerase poisons but that it does not
      predict clinical outcome in acute leukaemia.

PMID- 17549418
TI  - Epigenetic inactivation of the RAS-effector gene RASSF2 in lung cancers.
AB  - RASSF2, a member of the RAS association domain family 1 (RASSF1), is a candidate
      tumor suppressor gene (TSG) that is silenced by promoter hypermethylation in
      several human cancers. In this study, we examined the expression of RASSF2 mRNA
      and the promoter methylation status in lung cancer cell lines and in tumor
      samples of 106 primary non-small cell lung cancers (NSCLCs) by methylation
      specific PCR. RASSF2 expression was absent in 26% of small cell lung cancers
      (SCLCs; n=27 lines) and 50% of NSCLCs (n=42 lines). Promoter methylation of
      RASSF2 was found in 18% of the SCLC cell lines (n=22) and 62% of the NSCLC cell
      lines (n=26), and the methylation status was tightly associated with the loss of
      RASSF2 expression. RASSF2 expression was restored by treatment with 5-aza-2
      deoxycytidine and/or trichostatin-A in the NSCLC cell lines which were absent of
      the expression. RASSF2 methylation was found in 31% of primary NSCLC tumors, and
      methylation was more frequent in the specimens from non-smokers (18 of 40, 45%)
      than in the specimens from smokers (15 of 66, 23%, P=0.014). We also examined the
      association of RASSF2 methylation with mutations of KRAS and EGFR and with
      promoter hypermethylation of RASSF1A; however, we could not find a significant
      association between RASSF2 methylation and these genetic and epigenetic changes.
      Our results indicate that aberrant methylation of the RASSF2 gene with the
      subsequent loss of RASSF2 expression plays an important role in the pathogenesis
      of lung cancers.

PMID- 17549417
TI  - Selected flavonoids potentiate the toxicity of cisplatin in human lung
      adenocarcinoma cells: a role for glutathione depletion.
AB  - Adjuvant therapies that enhance the anti-tumor effects of cis
      diammineplatinum(II) dichloride (cisplatin, CDDP) are actively being pursued.
      Growing evidence supports the involvement of mitochondrial dysfunction in the
      anti-cancer effect of cisplatin. We examined the potential of using selective
      flavonoids that are effective in depleting tumor cells of glutathione (GSH) to
      potentiate cisplatin-mediated cytotoxicity in human lung adenocarcinoma (A549)
      cells. We found that cisplatin (40 microM, 48-h treatment) disrupts the steady
      state levels of mitochondrial respiratory complex I, which correlates with
      elevated mitochondrial reactive oxygen species (ROS) production and cytochrome c
      release. The flavonoids, 2',5'-dihydroxychalcone (2',5'-DHC, 20 microM) and
      chrysin (20 microM) potentiated the cytotoxicity of cisplatin (20 microM), which
      could be blocked by supplementation of the media with exogenous GSH (500 microM).
      Both 2',5'-DHC and chrysin were more effective than the specific inhibitor of GSH
      synthesis, L-buthionine sulfoximine (BSO, 20 microM), in inducing GSH depletion
      and potentiating the cytotoxic effect of cisplatin. These data suggest that the
      flavonoid-induced potentiation of cisplatin's toxicity is due, in part, to
      synergetic pro-oxidant effects of cisplatin by inducing mitochondrial
      dysfunction, and the flavonoids by depleting cellular GSH, an important
      antioxidant defense.

PMID- 17549419
TI  - Molecular approaches to the staging of head and neck carcinomas (review).
AB  - Despite the efforts during the last decades to improve clinical management and
      therapy, carcinomas of the head and neck still represent a disease with an
      unfavourable course. Over 50% of the patients die from their disease within 5
      years after diagnosis, with tumour recurrence, metastasis, and development of
      second primary neoplasms as major causes of treatment failure. In addition,
      surgical treatment of locally advanced disease often results in invalidating and
      disfiguring conditions that heavily affect patients' quality of life. Current
      criteria of tumour staging, essentially based on clinical and pathological
      assessment, fail to prove effective in providing reliable information on tumour
      prognosis or supporting an optimized planning of the therapies, prompting the
      identification of new and more accurate staging criteria. This review focuses on
      the impact of molecular biology in HNSCC staging, namely differentiation of
      second primary lesions from recurrence/metastasis and detection of lymph node
      micrometastasis, and highlights how the integration of the histopathological
      diagnosis with molecular analyses may result in a better management of HNSCC
      patients.

PMID- 17549420
TI  - DNA methylation markers of surfactant proteins in lung cancer.
AB  - Surfactant proteins play important roles in lung surfactant function and innate
      immunity. The DNA methylation state of 11 CpG sites of surfactant protein (SP)
      A1, -B, -C, and -D was determined using universal bead arrays. A total of 90
      cancerous and non-cancerous tissues from 23 patients with adenocarcinoma and 22
      with squamous cell carcinoma were studied. These were divided into a training set
      and a testing set. The results indicate that DNA methylation profiling of these
      CpGs is associated with lung cancer. Four CpG sites, SP-A1_370, SP-A1_1080, SP
      D_1170, and SP-D_1370, were hypomethylated in cancer and were significantly
      associated with both adenocarcinoma and squamous cell carcinoma, indicating that
      they have the potential to be used as biomarkers for lung cancer diagnosis and
      treatment. Normal lung tissues with a higher level of unmethylated SP-A1_1468 and
      SP-D_1170 CpG exhibited a higher level of SP-A1 and SP-D gene transcripts
      indicating that CpG methylation may play a role in gene expression. When the non
      cancerous tissues were compared to cancerous tissues in patients with
      adenocarcinoma, the methylation profile results of these 46 samples (23 cancerous
      and 23 non-cancerous) could be clustered into 4 groups by agglomerative nesting.
      The percentage of tumor samples in each group was 0, 58, 91, and 100,
      respectively. A similar pattern was observed in squamous cell carcinoma patients.
      We speculate that SP-A1 and SP-D are subject to methylation/demethylation
      regulatory mechanisms and are involved in lung cancer pathogenesis by virtue of
      their function in innate host defense and/or regulation of inflammation.

PMID- 17549421
TI  - Transfer of in vitro expanded T lymphocytes after activation with dendritomas
      prolonged survival of mice challenged with EL4 tumor cells.
AB  - Adoptive T cell transfer after in vitro expansion represents an attractive cancer
      immunotherapy. The majority of studies so far have been focusing on the expansion
      of tumor infiltrated lymphocytes (TIL) and some have shown very encouraging
      results. Recently, we have developed a unique tumor immune response activator,
      dendritomas, by fusion of dendritic cells and tumor cells. Animal studies and
      early clinical trials have shown that dendritomas are able to activate tumor
      specific immune responses. In this study, we hypothesized that naive T cells can
      be primed with dendritomas and expanded in vitro to develop an adoptive transfer
      therapy for patients who do not have solid tumors, such as leukemia. T cells were
      isolated and purified from lymph nodes of mice. The cells were then incubated
      with dendritomas made from syngeneic DCs and tumor cells and expanded in vitro
      using Dynabeads mouse CD3/CD28 T cell expander for approximately three weeks. The
      in vitro primed and expanded T cells showed tumor cell specific CTL activity and
      increased secretion of IFN-gamma. Tumor bearing mice receiving the in vitro
      expanded T cells survived significantly longer than control mice. Furthermore,
      the depletion of regulator T cells enhanced the survival of the mice that
      received the adoptive transfer therapy.

PMID- 17549422
TI  - Quantification of MET and hepatocyte growth factor/scatter factor expression in
      colorectal adenomas, carcinomas and non-neoplastic epithelia by quantitative
      laser scanning microscopy.
AB  - Hepatocyte growth factor (HGF)-MET signalling in cancer biology has been well
      characterized in multiple organ systems. Numerous investigations have described
      an up-regulation of c-met mRNA in human colorectal adenomas and carcinomas.
      However, a quantitative immunohistochemical analysis of MET and HGF protein
      levels in tumor tissues has not been reported previously. Formalin-fixed and
      paraffin-embedded tissues from 41 colorectal adenomas and 49 colorectal
      carcinomas were characterized by immunofluorescent staining using HGF- and MET
      specific antibodies. The immunoreactivity was evaluated by confocal laser
      scanning microscopy, computer-based image analysis and appropriate statistical
      tests. Normal colorectal mucosa, adenomas and carcinomas exhibited comparable
      levels of MET and HGF proteins. MET expression in carcinomas, although
      statistically not significant, demonstrated a tendency to correlate with the
      grade of differentiation. Correlations of MET and HGF with other clinico
      pathological variables including the extent of the mucinous component and the
      pTNM stage were not observed. The ratio of HGF in carcinoma vs. non-neoplastic
      tissue was significantly different between high and low carcinoma stage.
      Alterations of absolute levels of MET and HGF protein during the colorectal
      adenoma-carcinoma sequence were not significant. The presumed role of MET-HGF
      interactions in large bowel carcinogenesis may therefore be a result of or depend
      upon other regulatory factors involved in MET-mediated signalling pathways.

PMID- 17549423
TI  - Comparative integromics on the breast cancer-associated gene KIAA1632: clues to a
      cancer antigen domain.
AB  - Sequence analysis of protein-coding human genes in human breast and colorectal
      cancer recently identified the KIAA1632 gene as a potential contributor to
      neoplastic processes in breast cancer. In the present study, we characterized the
      KIAA1632 gene by computational methods: detailed investigation of the genomic
      structure, protein prediction, identification of orthologs in other species and
      phylogenetic analysis. The human KIAA1632 gene was located within human genome
      sequence AC090355 and consists of 44 exons. KIAA1632 is located on chromosome
      18q12.3-q21.1. These findings were determined by aligning the potential full
      length transcript NM_020964 to the genomic sequence. The existing predicted gene
      model could be refined based on these alignments (using additional EST data).
      Protein sequence was predicted from the full-length transcript and possible
      orthologs in other species were identified. Using rigorous phylogenetic methods
      we were able to draw conclusions about the evolutionary history of these
      proteins. Comparison of the protein sequences of KIAA1632 and its orthologs
      revealed a shared 'signature motif'. This 'signature motif' was found in three
      well-characterized cancer antigens, raising the hypothesis of a common 'signature
      motif' for a certain group of cancer antigens.

PMID- 17549424
TI  - Diversity of common alternative splicing variants of human cytochrome P450 1A1
      and their association to carcinogenesis.
AB  - Cytochrome P450 1A1 (CYP1A1) belongs to the enzymes of biotransformation of phase
      I. CYP1A1 performs the catalytic activation of exogenous and endogenous
      substrates to more carcinogenic metabolites. Overexpression of the wild-type and
      a recently described splice variant (CYP1A1v, ovarian cancer) are attributed to
      neoplastic transformation. Here we describe novel CYP1A1 splicing variants
      commonly and frequently transcribed in leucocytes of healthy volunteers,
      separated from variants exclusively expressed in tumour cell lines.
      Interestingly, all the novel splicing variants in leukocytes are generated by
      employing of two nested splice site pairs, one outer canonical and one inner non
      canonical splice site pair, within the exon 2 of the human CYP1A1. In general,
      the frequent presence of common splicing variants in healthy volunteers has to be
      consider as a physiological feature of human CYP1A1 transcription process, rather
      than a signature of carcinogenesis.

PMID- 17549425
TI  - Comparative integromics on JMJD1C gene encoding histone demethylase: conserved
      POU5F1 binding site elucidating mechanism of JMJD1C expression in
      undifferentiated ES cells and diffuse-type gastric cancer.
AB  - Epigenetic modifications of genomic DNA and histones alter the chromatin
      structure to regulate the accessibility of transcription factors to the promoter
      or enhancer regions. In 2003, we identified and characterized JMJD1C (TRIP8)
      consisting of TRI8H1 domain with C2HC4-type zinc finger-like motif, TRI8H2 domain
      with thyroid hormone receptor beta-binding region, and JmjC domain. JMJD1A
      (TSGA), JMJD1B (5qNCA) and JMJD1C with the common domain architecture are histone
      H3K9 demethylases implicated in the nuclear hormone receptor-based
      transcriptional regulation. Here, comparative integromics on JMJD1C gene is
      reported. JMJD1C variant 1, previously reported, consists of exons 1, 2 and 3-26,
      while JMJD1C variant 2 characterized in this study was transcribed from novel
      exon 1B located 5' to exon 3. Four human JMJD1C ESTs were transcribed from exon
      1, while 14 human JMJD1C ESTs from exon 1B. All of 26 mouse Jmjd1c ESTs were
      transcribed from exon 1b. These facts indicate that JMJD1C variant 2 transcribed
      from exon 1B was the major transcript. Human JMJD1C variant 2 with TRI8H1,
      TRI8H2, and JmjC domains showed 85.7% total-amino-acid identity with mouse
      Jmjd1c. Human JMJD1C mRNA was expressed in undifferentiated embryonic stem (ES)
      cells, pancreatic islet, diffuse-type gastric cancer, and other tissues or
      tumors. Mouse Jmjd1c mRNA was expressed in fertilized egg, blastocyst,
      undifferentiated ES cells, embryonic germ cells, c-Kit+/Sca-1+/Lin- hematopoietic
      stem cells, pancreatic islet, and other tissues. Comparative genomics analyses
      revealed that binding sites for POU5F1 (OCT3/OCT4), AP-1, and bHLH transcription
      factors within the promoter region located 5' to exon 1B of human JMJD1C gene
      were conserved in chimpanzee, cow, mouse and rat JMJD1C orthologs. POU5F1
      mediated expression of JMJD1C histone demethylase is implicated in the
      reactivation of silenced genes in undifferentiated ES cells, pancreatic islet,
      and diffuse-type gastric cancer.

PMID- 17549426
TI  - Molecular impacts of rapamycin-based drug combinations: combining rapamycin with
      gemcitabine or imatinib mesylate (Gleevec) in a human leiomyosarcoma model.
AB  - Drug combinations may provide a therapeutic benefit in treating cancer patients.
      However when considering a drug combination, it is important to assess how the
      molecular impact of the combination relates to the effects manifested by each
      drug alone and whether or not it varies depending on the tumor type. In this
      study, we have analyzed the molecular impact on a human leiomyosarcoma cell line
      (SK-LMS-1) of a combination consisting of the mTOR inhibitor rapamycin and either
      the anti-metabolite drug gemcitabine (Gemzar) or the protein tyrosine kinase
      inhibitor imatinib mesylate (Gleevec, STI571). We show that imatinib mesylate
      depolarizes the mitochondrial membrane potential (DeltaPhim) and inhibits protein
      tyrosine phosphorylation, but displays only minor effects on cell proliferation
      when added alone or in combin-ation with rapamycin. Gemcitabine or rapamycin,
      when added alone, inhibit protein tyrosine phosphorylation as well as
      phosphorylation of the MAP kinases ERK1/2. Both drugs also affect the cell cycle,
      arresting the cells at the S or G1 phase respectively. Rapamycin elevates
      significantly DeltaPhim but produces only a moderate effect on cell growth.
      Gemcitabine inhibits considerably cell growth but exerts no effect on DeltaPhim.
      Combining gemcitabine and rapamycin produces a major effect on the cell cycle,
      elevates the DeltaPhim even further and maintains the molecular impacts exerted
      by each single drug. Therefore, consistent with our clinical observation, these
      results suggest that combining gemcitabine and rapamycin may be beneficial in
      treating leiomyosarcoma patients.

PMID- 17549427
TI  - Phytoaccumulation, interaction, toxicity and remediation of cadmium from
      Helianthus annuus L. (sunflower).
AB  - An investigation was conducted to study the interaction between Cd and Ca, Zn and
      organic matter for Cd-phytoremediation in sunflower on the alluvium soil of the
      Sheila Dhar Institute (SDI) experimental farm, Allahabad (India). Application of
      40 ppm Zn produced 11.18% extra dry matter (DM) content and 5.8% extra seed yield
      over the control. We recommended 1.0% Ca, 40 ppm Zn and 20 tons/ha of compost to
      enhance dry matter yield and diminish the Cd accumulation in 15 ppm Cd-
      ethylenediaminetetraacetic (EDTA)-treated plots up to 1/12 folds in sunflower
      (<0.21 ppm), which indicated phytoremediation of Cd-contaminated soil through
      soil-plant-rhizospheric processes.

PMID- 17549428
TI  - The effect of spinal anaesthesia on urethral function.
AB  - This study was to assess the effect of spinal anaesthesia on urethral retro
      resistance pressure (URP), cough pressures and tendency to leak. The population
      consisted of 32 women undergoing a tension-free vaginal tape (TVT) operation
      under a spinal anaesthetic. URP, cough pressures and an assessment of the degree
      of leak were performed before the spinal anaesthetic was placed. A standard
      anaesthetic technique was used, and measurements were repeated after the spinal
      anaesthetic was inserted. The degree of leak was assessed on a five-point scale
      with 350 ml in the bladder. The cough pressures and URP values were averaged over
      three or more measurements. The mean URP value fell from 75.0 to 54.0 cm/H2O (p =
      0.0003) after the spinal was inserted. There was a non-significant fall in mean
      cough pressure from 85.0 to 67.5 cm/H2O (p = 0.06). The degree of leakage
      increased (p = 0.005). Spinal anaesthesia causes a fall in the resistance in the
      urethra but does not cause a significant fall in the pressure generated by a
      cough. Women are more likely to leak after coughing during the TVT operation
      under spinal anaesthesia than they are before the spinal is inserted. The cough
      test under spinal anaesthesia does not mimic the result of coughing without a
      spinal.

PMID- 17549430
TI  - Transobturator slings for stress incontinence: using urodynamic parameters to
      predict outcomes.
AB  - The purpose of this study is to evaluate the ability of preoperative urodynamic
      urethral function parameters to predict the success rate of transobturator slings
      (TOS). Seventy women urodynamically diagnosed with stress incontinence with
      urethral hypermobility underwent a Monarc TOS (American Medical Systems,
      Minnetonka, USA). Postoperative continence status was correlated with
      preoperative urodynamic urethral function parameters. Mathematical modeling was
      used to determine whether urodynamic parameters can be used to predict
      postoperative continence. Average follow-up was 8.1 (6-12) months; 56 (80%)
      patients were continent based on a standardized stress test and subjective
      report. The median Valsalva leak point pressure at 150 cc (VLPP150) in the
      failures and successes was not different (p = 0.12). The median VLPP at
      cystometric capacity (VLPPcap) in the failures was 32 cmH2O compared to 71 cmH2O
      in the successes (p < 0.001). The maximum urethral closure pressure (MUCP) had a
      median of 20 cmH2O in the failures and 45 cmH2O in the successful patients (p <
      0.001). No correlation existed between the degree of urethral hypermobility, as
      measured by the cotton swab test, and surgical success (p = 0.17). There was no
      correlation between level of preoperative urethral function and persistent
      overactive bladder symptoms, post-void residual, voids/day, and nocturia. Using a
      combined model, the cutoff values of VLPPcap > 60 cmH2O and MUCP > 40 cmH2O were
      the most predictive of surgical success, revealing a sensitivity of 83% (0.55,
      0.95) and specificity of 79% (0.67, 0.88). A combination of urodynamic parameters
      can be used to predict continence rates after a TOS. A TOS should be used with
      caution in women with impaired urethral function.

PMID- 17549429
TI  - Rehabilitation versus drug therapy for urge urinary incontinence: long-term
      outcomes.
AB  - The objective of this study was to compare the residual effect of a 3-month
      rehabilitation treatment and a standard drug treatment for urge urinary
      incontinence (UUI) 21 months post intervention. Forty-four women (ages 27-68
      years) who were diagnosed with overactive bladder (OAB) were divided into 2
      treatment groups over 3 months: 24 women received rehabilitation (REH) and 20
      women were treated with medication (MED) (oxybutynin ER). Outcomes measures
      included frequency of urination, quality of life (QoL), and number of side
      effects (no/SE), which were measured upon entry into the study (entry),
      completion of the intervention (3 months), and at follow-up 3 and 21 months after
      completion of treatment. In the follow-up period, there was a significant group
      time interaction effect on freq/day and freq/night (p < 0.01). At the end of
      follow-up, the mean number of no/SE was significantly greater in the MED group
      compared to the REH group (3.3 +/- 0.5 vs 2.4 +/- 0.4; p < 0.05). A significant
      negative association was found between the urinary symptoms and the I-QoL at the
      21-month follow-up (r (p) = -0.45 to-0.57, p < 0.05). In the long-term, the REH
      patients maintained and even improved the achievements of the intervention period
      while the MED patients deteriorated to baseline values in urinary frequency. The
      suggestion for future work is to investigate the effect of each REH treatment
      component on UUI symptoms.

PMID- 17549431
TI  - The non-phosphorylating glyceraldehyde-3-phosphate dehydrogenase (GAPN) of
      Sulfolobus solfataricus: a key-enzyme of the semi-phosphorylative branch of the
      Entner-Doudoroff pathway.
AB  - Archaea utilize a branched modification of the classical Entner-Doudoroff (ED)
      pathway for sugar degradation. The semi-phosphorylative branch merges at the
      level of glyceraldehyde 3-phosphate (GAP) with the lower common shunt of the
      Emden-Meyerhof-Parnas pathway. In Sulfolobus solfataricus two different GAP
      converting enzymes-classical phosphorylating GAP dehydrogenase (GAPDH) and the
      non-phosphorylating GAPDH (GAPN)-were identified. In Sulfolobales the GAPN
      encoding gene is found adjacent to the ED gene cluster suggesting a function in
      the regulation of the semi-phosphorylative ED branch. The biochemical
      characterization of the recombinant GAPN of S. solfataricus revealed that-like
      the well-characterized GAPN from Thermoproteus tenax-the enzyme of S.
      solfataricus exhibits allosteric properties. However, both enzymes show some
      unexpected differences in co-substrate specificity as well as regulatory fine
      tuning, which seem to reflect an adaptation to the different lifestyles of both
      organisms. Phylogenetic analyses and database searches in Archaea indicated a
      preferred distribution of GAPN (and/or GAP oxidoreductase) in hyperthermophilic
      Archaea supporting the previously suggested role of GAPN in metabolic
      thermoadaptation. This work suggests an important role of GAPN in the regulation
      of carbon degradation via modifications of the EMP and the branched ED pathway in
      hyperthermophilic Archaea.

PMID- 17549432
TI  - Long-term results of trabeculectomy with mitomycin C applied under the scleral
      flap.
AB  - PURPOSE: The objective of this study was to look at the long-term safety, and the
      effectiveness on intraocular pressure, of trabeculectomy and mitomycin C (MMC)
      applied under the scleral flap. METHODS: All patients undergoing trabeculectomy
      and MMC application during the period June 1992-August 1995 were included. Data
      on 30 eyes of 25 patients were reviewed. We looked at sociodemographic variables,
      intraocular pressure (IOP) control, visual acuities and bleb morphology. Bleb
      related and other complications were also noted. Statistical analysis was
      performed with Student's paired t-test, and Kaplan-Meier life table analysis was
      utilised for IOP control. RESULTS: The mean age of patients (12 male and 13
      female) was 56 years (range 7-79 years), with a mean follow-up period of 8.7
      years (range 5-11 years). There was one eye with blebitis/endophthalmitis at 4
      years, and one eye developed hypotonous maculopathy. Ten eyes were noted to have
      poor bleb morphology due to long-standing fibrosis, and the majority of these
      underwent further surgical intervention with 5-fluorouracil (5FU) needling. The
      IOP control showed good results, with mean IOP falling from a preoperative level
      of 24.8-15.2 mmHg at the last visit, with good probability of maintenance in the
      longer term. The main reason for reduced vision was pre-existing co-morbidity and
      development of lenticular opacities. CONCLUSION: In the series with the longest
      follow-up period our study showed that trabeculectomy augmented with MMC under
      the scleral flap in these difficult cases can achieve good long-term IOP control
      and is associated with minimal long-term complications.

PMID- 17549433
TI  - Escherichia coli malate dehydrogenase, a novel solubility enhancer for
      heterologous proteins synthesized in Escherichia coli.
AB  - Using 2-dimensional gel electrophoresis, the Escherichia coli proteome response
      to a heat-shock stress was analyzed and a 1.6-fold increase of malate
      dehydrogenase was observed even under the heat-shock condition where the total
      number of soluble proteins decreased by about 5%. We subsequently demonstrated
      that, as an N-terminus fusion expression partner, malate dehydrogenase
      facilitated the folding of, and dramatically increased the solubility of, many
      aggregation-prone heterologous proteins in E. coli cytoplasm. Therefore, malate
      dehydrogenase is well suited for production of a biologically active fusion
      mutant of cutinase (Pseudomonas putida origin) that is currently of considerable
      to biotechnology and commercial industries.

PMID- 17549435
TI  - Lipase-catalyzed regioselective synthesis of steryl (6'-O-acyl)glucosides.
AB  - The regioselective acylation of cholesteryl beta-D-glucoside, at the C-6 of the
      glucose moiety, was achieved using microbial lipases in organic solvents. With
      palmitic acid as an acyl donor 81 or 63% conversions of cholesteryl glucoside to
      its 6'-O-palmitoyl derivative were obtained using Candida antarctica or
      Rhizomucor miehei enzymes, respectively. High yields (64-92%) were also obtained
      with fatty acids 6:0-22:0 and 16:1 (n-7). The synthesis of cholesteryl (6'-O
      palmitoyl)glucoside was also achieved via transesterification, using mono-, di-
      and tri-palmitoylglycerols or methyl and ethyl palmitate as acyl sources. With R.
      miehei lipase transesterification between methyl palmitate (80 mM) and
      cholesteryl glucoside (1 mM) proceeded after 24 h with a nearly quantitative
      yield (97%).

PMID- 17549434
TI  - Expression of a truncated ripening inhibitor (RIN) protein from tomato and
      production of an anti-RIN antibody.
AB  - The tomato ripening mutant, ripening inhibitor (rin), whose fruits fails to
      ripen, has been identified and widely studied. The RIN gene has been cloned. Here
      we present the expression of a truncated form of the RIN protein from tomato and
      the preparation of a polyclonal antibody against it. The resulting antibody
      recognized the RIN of crude protein extracts from different tomato tissues. The
      protein level of RIN in tomato was detected with this antibody by western blot,
      which suggested the accumulation of RIN protein increased gradually during tomato
      fruit ripening.

PMID- 17549436
TI  - Oxidation of butane to butanol coupled to electrochemical redox reaction of
      NAD+/NADH.
AB  - A crude cell extract from a butane-utilizing bacterium, Alcaligenes sp.,
      catalyzed the oxidation of butane to butanol coupled to NADH. A graphite
      electrode modified with Neutral Red (NR-electrode) catalyzed the reduction of
      NAD(+) to NADH. About 4.9 mM butanol was produced from 50% n-butane/O(2) mixture
      through the combined reactions of the crude enzyme and the NR-electrode in 250 ml
      reactor for 3 h.

PMID- 17549437
TI  - FV Leiden mutation and risk of recurrent venous thromboembolism in Serbian
      population.
AB  - The absolute rate of recurrence of venous thromboembolism (VTE) is approximately
      5% per year. There is a lower rate of recurrence in provoked VTE, and higher in
      idiopathic one. So far, there is no consensus whether hereditary thrombophilia
      should be considered as a persistent risk factor, and whether it requires long
      term anticoagulant therapy. The aim of our study was to estimate the risk of
      recurrent VTE in patients carrying FV Leiden mutation in Serbian population. In
      retrospective study (1994-2006), we have evaluated the risk of recurrent VTE in
      56 patients who are carriers of FV Leiden mutation, in comparison to group
      consisting of 56 patients non-carriers of FV Leiden mutation. Patients with FII
      G20210A and MTHFR C677T mutations, antiphospholipid antibodies, antithrombin III,
      protein C or protein S deficiency, malignancies and diabetes were excluded from
      the study. Recurrent VTE occurred in 44.6% of the patients, carriers of the FV
      Leiden mutations, vs. 26.7% in non-carriers group (P<0.05). The incidence rate
      was 3.7 and 2.2% per year, respectively. The estimated relative risk of
      recurrence for FV Leiden carriers was 1.67 (95% CI 0.99-2.81, P=0.049). The 60%
      of patients with mutation and only 13% without mutation develop rethrombosis
      during first year after discontinuance of therapy (P<0.01). In our study patients
      with symptomatic VTE who are carriers of the FV Leiden gene mutations have a
      higher risk of recurrent VTE than non-carriers. Our data suggest the importance
      of the FV Leiden mutation detection and the estimation of the clinical condition
      for successful secondary prophylaxis of VTE.

PMID- 17549438
TI  - Regulation of excitation by GABA(A) receptor internalization.
AB  - Neuronal inhibition is of paramount importance in maintaining the delicate and
      dynamic balance between excitatory and inhibitory influences in the central
      nervous system. GABA (gamma-aminobutyric acid), the primary inhibitory
      neurotransmitter in brain, exerts its fast inhibitory effects through
      ubiquitously expressed GABA(A) receptors. Activation of these heteropentameric
      receptors by GABA results in the gating of an integral chloride channel leading
      to membrane hyperpolarization and neuronal inhibition. To participate in
      neurotransmission, the receptor must reside on the cell surface. The trafficking
      of nascent receptors to the cell surface involves posttranslational modification
      and the interaction of the receptor with proteins that reside within the
      secretory pathway. The subsequent insertion of the receptor into specialized
      regions of the plasma membrane is dictated by receptor composition and other
      factors that guide insertion at synaptic or perisynaptic/extrasynaptic sites,
      where phasic and tonic inhibition are mediated, respectively. Once at the cell
      surface, the receptor is laterally mobile and subject to both constitutive and
      regulated endocytosis. Following endocytosis the receptor undergoes either
      recycling to the plasma membrane or degradation. These dynamic processes
      profoundly affect the strength of GABAergic signaling, neuronal inhibition, and
      presumably synaptic plasticity. Heritable channelopathies that affect receptor
      trafficking have been recently recognized and compelling evidence exists that
      mechanisms underlying acquired epilepsy involve GABA(A) receptor internalization.
      Additionally, GABA(A) receptor endocytosis has been identified as an early event
      in the ischemic response that leads to excitotoxicity and cell death. This
      chapter summarizes what is known regarding the regulation of receptor trafficking
      and cell surface expression and its impact on nervous system function from both
      cell biology and disease perspectives.

PMID- 17549439
TI  - The role of GABA(B) receptors in the regulation of excitatory neurotransmission.
AB  - GABA(B) receptors are the metabotrophic receptors for GABA. They are members of
      the G-protein coupled superfamily of receptors but are highly unusual as they are
      made up of a dimer of 7-transmembrane spanning subunits. The receptors are widely
      distributed throughout the central nervous system where they act post
      synaptically to cause a long-lasting hyperpolarisation through the activation of
      a potassium conductance. They are also present pre-synaptically where they act as
      auto and heteroreceptors to inhibit neurotransmitter release. GABA(B) receptors
      play a complex role in the regulation of excitatory transmission and their
      activation can have both inhibitory and dis-inhibitory effects. This has profound
      physiological and behavioural consequences including modification of LTP and
      memory, regulation of seizure activity and nociception.

PMID- 17549440
TI  - [Necrolytic migratory erythema in glucagonoma syndrome].
AB  - The glucagonoma syndrome is a rare disease in which a typical skin lesion,
      necrolytic migratory erythema, is often one of the presenting symptoms. A 68-year
      old woman developed erythematous polycyclic migratory lesions with advancing
      scaling borders and crusts over several years. Skin biopsies, laboratory studies
      and imaging confirmed the diagnosis of necrolytic migratory erythema as part of a
      glucagonoma syndrome.

PMID- 17549441
TI  - RhoC is essential for the metastasis of gastric cancer.
AB  - Rho family members are known to regulate malignant transformation and motility of
      cancer cells, but the clinicopathological significance of RhoC remains unclear
      yet in the case of gastric cancer. In this study, we evaluated the protein
      expression level of RhoC in gastric cancer tissues and cell lines. Results showed
      that only weak staining of RhoC was detected in 3 of 33 non-tumorous cases by
      immunohistochemistry. The expression of RhoC was significantly higher in gastric
      cancer tissues (23/42, 54.8%) than in non-tumorous tissues (p < 0.01). Further
      analysis demonstrated that RhoC had high specificity (80.0%) in detecting gastric
      carcinomas with metastatic potential. RhoC was positively expressed in 18 out of
      20 metastases (90.0%), even higher than that in primary gastric cancer tissues.
      Western blot showed that RhoC was up-regulated in five different gastric cancer
      cell lines but not expressed in SV40-transformed immortal gastric epithelial cell
      GES-1. Overexpression of RhoC GTPase in GES-1 cells could produce the motile and
      invasive phenotype but did not alter the monolayer growth rate. To further study
      the functions of RhoC, we took the powerful siRNA technology to knock down the
      expression of RhoC in SGC7901 cells. It was shown that down-regulation of RhoC
      did not affect the proliferation of SGC7901 cells. However, interference of RhoC
      expression could inhibit migration, invasion, and anchorage-independent growth of
      SGC7901 cells. In conclusion, RhoC may play a very important role in the
      metastasis of gastric carcinoma. Therapeutic strategies targeting RhoC and RhoC
      mediated pathways may be a novel approach for treating metastasis of gastric
      cancer.

PMID- 17549442
TI  - Protein kinase C-beta and -delta isoenzymes promote arachidonic acid production
      and proliferation of MonoMac-6 cells.
AB  - In this study, we investigated the putative roles of certain protein kinase C
      (PKC) isoenzymes in the regulation of proliferation and arachidonic acid (AA)
      release in the human monocytoid MonoMac-6 cell line. Experiments employing
      specific PKC inhibitors and molecular biological methods (RNA-interference,
      recombinant overexpression) revealed that the two dominantly expressed isozymes,
      i.e., the "conventional" cPKCbeta and the "novel" nPKCdelta, promote AA
      production and cellular proliferation. In addition, using different phospholipase
      A(2) (PLA(2)) inhibitors, we were able to show that the calcium-independent
      iPLA(2) as well as diacylglycerol lipase (but not the cytosolic PLA(2)) function
      as "downstream" targets of cPKCbeta and nPKCdelta. In addition, we have also
      found that, among the other existing PKC isoforms, cPKCalpha plays a minor
      inhibitory role, whereas nPKCvarepsilon and aPKCzeta apparently do not regulate
      these cellular processes. In conclusion, in this paper we provide the first
      evidence that certain PKC isoforms play pivotal, specific, and (at least partly)
      antagonistic roles in the regulation of AA production and cellular proliferation
      of human monocytoid MonoMac-6 cells.

PMID- 17549443
TI  - [Epidemiology and perspectives in traumatology of the elderly].
AB  - Corresponding to the demographic development, fractures of the humerus, wrist, or
      hip will occur noticeably more often during the next four decades. The number of
      patients with hip fractures will increase to 170% of present-day numbers, and in
      the age group >80 years to 250%. Trauma surgical departments should train their
      staff as well as adapt their workflows and ambient conditions to this demanding
      clientele to be prepared for these changes. For the elderly, a fracture may lead
      to need for permanent home care, which is why postoperative transfer to
      ambulatory care is especially important. The expected cost progression in
      traumatology of the elderly may be moderated by the conjunction of inpatient and
      ambulatory care, the utilization of synergies among the different service types,
      and by implementation of prophylaxis for osteoporosis and falls.

PMID- 17549444
TI  - [Local intravenous fibrinolysis in deep cerebral vein thrombosis].
AB  - Acute cerebral vein and dural sinus thrombosis are usually treated with
      unfractionated intravenous heparin. Progression of symptoms after appropriate
      heparin dosage appears to be a rare event. In the literature only single case
      reports or small case series dealing with local intravenous fibrinolysis are
      available. Here we describe a 44-year-old woman with progressive thrombosis of
      the sinus rectus and right sinus transversus upon an appropriate dosage of
      heparin who was successfully treated with urokinase 12 h after symptom onset.
      This case demonstrates that local thrombolysis should be discussed in patients
      with progression of the clinical or radiological picture under sufficient heparin
      therapy.

PMID- 17549445
TI  - [The role of uveitis in demyelinating diseases of the central nervous system].
AB  - An involvement of the visual system can be found in many neurologic diseases.
      Especially demyelinating processes of the central nervous system (CNS) and
      multiple sclerosis (MS) in particular present with a variety of ophthalmological
      abnormalities. While optic neuritis (ON) is known to be a positive predictor for
      the development of MS and can be considered a symptom of the disease, the high
      frequency of uveitis observed in MS patients seems to occur rather in the context
      of a general predisposition for autoimmune disorders. However, MS-associated
      uveitis can precede the onset of neurological symptoms by many years and shows
      response to treatment with steroids and interferons, suggesting the presence of
      similar underlying pathogenic mechanisms. Therefore, further studies are
      warranted in order to reveal whether administration of early immunomodulatory
      therapy can delay or even prevent the clinical manifestation of MS in a distinct
      subgroup of patients presenting with uveitis.

PMID- 17549446
TI  - [Problems of evidence-based medicine in psychopharmacotherapy: problems of
      evidence grading and of the evidence basis for complex clinical decision making].
AB  - Psychopharmacotherapy should now be regulated in the sense of evidence based
      medicine, as is the case in other areas of therapeutic medicine. In general, this
      is a meaningful development which will have a positive impact on routine health
      care. However, related problems should not be ignored. One important problem is
      the different definition of degrees of evidence. If placebo-controlled studies
      are prioritized, evidence deviates too much from the conditions of routine
      clinical care. However, the restriction to active comparative trials could lead
      to false conclusions about efficacy. In addition, if the focus is placed on the
      results of meta-analyses instead of considering relevant single studies, the
      result is a decision making logic contrary to that of the licensing process.Due
      to inherent methodological problems of the meta-analytical approach, the
      narrative, systematic review should retain its traditional importance and be used
      to provide a complementary view. Attempts to regulate psychopharmacotherapy in
      the sense of evidence based medicine come closer to their limits the more complex
      the clinical situation and the respective decision making logic are. Even in
      times of evidence based medicine, a large part of complex clinical decision
      making in psychopharmacotherapy still relies more on a consensus about clinical
      experience and traditions than on relevant empirical databases.

PMID- 17549447
TI  - Characterization of a dUTPase from the hyperthermophilic archaeon Thermococcus
      onnurineus NA1 and its application in polymerase chain reaction amplification.
AB  - Genomic analysis of the hyperthermophilic archaeon Thermococcus onnurineus NA1
      (TNA1) revealed the presence of a 471-bp open reading frame with 93% similarity
      to the dUTPase from Pyrococcus furiosus. The dUTPase-encoding gene was cloned and
      expressed in Escherichia coli. The purified protein hydrolyzed dUTP at about a 10
      fold higher rate than dCTP. The protein behaved as a dimer in gel filtration
      chromatography, even though it contains five motifs that are conserved in all
      homotrimeric dUTPases. The dUTPase showed optimum activity at 80 degrees C and pH
      8.0, and it was highly thermostable with a half-life (t (1/2)) of 170 min at 95
      degrees C. The enzymatic activity of the dUTPase was largely unaffected by
      variations in MgCl(2), KCl, (NH(4))(2)SO(4), and Triton X-100 concentrations,
      although it was reduced by bovine serum albumin. Addition of the dUTPase to
      polymerase chain reactions (PCRs) run with TNA1 DNA polymerase significantly
      increased product yield, overcoming the inhibitory effect of dUTP. Further,
      addition of the dUTPase allowed PCR amplification of targets up to 15 kb in
      length using TNA1 DNA polymerase. This enzyme also improved the PCR efficiency of
      other archaeal family B type DNA polymerases, including Pfu and KOD.

PMID- 17549448
TI  - [Postoperative imaging of paranasal sinuses].
AB  - The radiological interpretation of postoperative changes of the paranasal sinuses
      requires knowledge of why and how the surgical intervention was performed and
      what the basic clinical findings were. It is important to know whether there was
      an inflammation, a reconstructive procedure, or a tumorous process. Multidetector
      computed tomography (MDCT) evaluated in a high-resolution bone window level
      setting represents the method of choice for imaging after nonfunctional and
      functional procedures after inflammatory changes as well as for imaging after
      reconstructive surgery because of facial trauma or before dental implantation. In
      the postoperative follow-up of tumor patients contrast-enhanced MDCT evaluated in
      a soft tissue window and bone window and especially magnetic resonance imaging
      (MRI) represent the standard. In many cases it is possible to differentiate tumor
      recurrence from inflammation with the help of contrast-enhanced multiplanar MRI
      and to detect bone marrow changes prior to CT.

PMID- 17549449
TI  - Enhanced proportion of small adipose cells in insulin-resistant vs insulin
      sensitive obese individuals implicates impaired adipogenesis.
AB  - AIMS/HYPOTHESIS: The biological mechanism by which obesity predisposes to insulin
      resistance is unclear. One hypothesis is that larger adipose cells disturb
      metabolism via increased lipolysis. While studies have demonstrated that cell
      size increases in proportion to BMI, it has not been clearly shown that adipose
      cell size, independent of BMI, is associated with insulin resistance. The aim of
      this study was to test this widely held assumption by comparing adipose cell size
      distribution in 28 equally obese, otherwise healthy individuals who represented
      extreme ends of the spectrum of insulin sensitivity, as defined by the modified
      insulin suppression test. SUBJECTS AND METHODS: Subcutaneous periumbilical
      adipose tissue biopsy samples were fixed in osmium tetroxide and passed through
      the Beckman Coulter Multisizer to obtain cell size distributions. Insulin
      sensitivity was quantified by the modified insulin suppression test. Quantitative
      real-time PCR for adipose cell differentiation genes was performed for 11
      subjects. RESULTS: All individuals exhibited a bimodal cell size distribution.
      Contrary to expectations, the mean diameter of the larger cells was not
      significantly different between the insulin-sensitive and insulin-resistant
      individuals. Moreover, insulin resistance was associated with a higher ratio of
      small to large cells (1.66 +/- 1.03 vs 0.94 +/- 0.50, p = 0.01). Similar cell
      size distributions were observed for isolated adipose cells. The real-time PCR
      results showed two- to threefold lower expression of genes encoding markers of
      adipose cell differentiation (peroxisome proliferator-activated receptor gamma1
      [PPARgamma1], PPARgamma2, GLUT4, adiponectin, sterol receptor element binding
      protein 1c) in insulin-resistant compared with insulin-sensitive individuals.
      CONCLUSIONS/INTERPRETATION: These results suggest that after controlling for
      obesity, insulin resistance is associated with an expanded population of small
      adipose cells and decreased expression of differentiation markers, suggesting
      that impairment in adipose cell differentiation may contribute to obesity
      associated insulin resistance.

PMID- 17549450
TI  - Fatty liver and obesity: phenotypically correlated but genetically distinct
      traits in a mouse model of type 2 diabetes.
AB  - AIMS/HYPOTHESIS: Obesity and fatty liver are commonly associated with type 2
      diabetes, but the genetic and functional bases linking fatty liver with obesity
      and diabetes are largely unknown. Our aim was to investigate the association of
      fatty liver with obesity and other diabetes-related phenotypes and to define the
      genetic control of obesity and fatty liver. MATERIALS AND METHODS: We established
      306 F2 mice by crossing Nagoya-Shibata-Yasuda (NSY) mice, an animal model of type
      2 diabetes, with control C3H mice, and analysed their phenotypes. Whole-genome
      screening of F2 mice was performed to identify the loci responsible for fatty
      liver and obesity. RESULTS: A strong association of fatty liver with obesity,
      hyperinsulinaemia and hyperglycaemia was observed in F2 mice. Using whole-genome
      screening in 306 F2 mice, we mapped a new locus for fatty liver (Fl1n) on
      chromosome 6 (maximum logarithm of odds score [MLS] 10.0) and one for body weight
      (Bw1n) on chromosome 7 (MLS 5.1). Fl1n was linked to epididymal fat weight as
      well as fatty liver, but its effects were opposite in the two tissues in that the
      NSY allele increased liver fat but decreased epididymal fat, suggesting a role of
      Fl1n in partitioning of fat mass. The sequence of peroxisome proliferator
      activated receptor gamma (Pparg), a candidate for Fl1n, showed allelic variation
      between NSY and C3H mice. CONCLUSIONS/INTERPRETATION: These data suggest that
      fatty liver and obesity are phenotypically related but genetically independent.
      Loci homologous to Fl1n and Bw1n are good candidate genes for susceptibility to
      fatty liver and obesity in humans.

PMID- 17549451
TI  - Urinary biomarker of oxidative stress correlating with outcome in critically
      septic patients.
AB  - OBJECTIVE: To determine whether urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG), an
      in vivo parameter of oxidative stress, is correlated with the outcome of
      critically septic patients. DESIGN AND SETTING: Clinical outcome study in an
      adult medical ICU. PATIENTS: Eighty-five consecutive septic patients: 59 men and
      26 women. MEASUREMENTS AND RESULTS: Urinary 8-OHdG was analyzed using isotope
      dilution liquid chromatography with tandem mass spectrometry (LC/MS/MS). ICU
      mortality in these 85 septic patients was 25.9% (n = 22) and hospital mortality
      38.8% (n = 33). APACHE II scores of survivors on day 1, on day 3, and the
      difference between them differed significantly from those of nonsurvivors (day 1,
      21.0 +/- 7.1 vs. 25.9 +/-8.0; day 3, 15.0 +/- 5.8 vs. 23.2 +/- 8.3; difference,
      6.0 +/- 5.5 vs. 1.7 +/- 6.6). Urinary 8-OHdG was significantly lower in survivors
      than in nonsurvivors on day 1 (1.8 +/- 2.4 vs. 3.0 +/- 2.4). The area under
      receiver operating characteristic curve analysis for the association between day
      1 urinary 8-OHdG and ICU mortality was 0.71. The comparison performed upon
      discharge from hospital revealed similar results. CONCLUSIONS: This is a
      preliminary study. The excretion of the urinary 8-OHdG, as measured using isotope
      dilution LC/MS/MS, as the APACHE II score, were correlated with the outcome of
      critically septic patients in medical ICU.

PMID- 17549452
TI  - Comparison of two methods for enhanced continuous circulatory monitoring in
      patients with septic shock.
AB  - OBJECTIVE: To compare a modified pulmonary artery catheter (PAC) and pulse
      contour analysis by the PiCCO (Pulsion Medical Systems, Munich, Germany) system
      for continuous assessment of cardiac output in patients with septic shock. In
      addition, to assess the relationships between an index of global end-diastolic
      volume (GEDV) derived by the PiCCO system with traditional PAC-derived indicators
      of filling: central venous pressure; pulmonary artery occlusion pressure; and
      right ventricular end-diastolic volume (RVEDV). DESIGN: Prospective cohort study.
      SETTING: Surgical intensive care unit of a university hospital. PATIENTS AND
      PARTICIPANTS: 14 patients with septic shock. INTERVENTIONS: None. MEASUREMENTS
      AND RESULTS: A significant correlation was found between continuous cardiac
      output by PAC (CCO(PAC)) and by pulse-contour analysis (r (2) = 0.714, p <
      0.0001), accompanied by a bias of 0.1 l min(-1) and a precision of 2.7 l min(-1).
      The correlation between CCO(PAC) and cardiac output measured by
      transcardiopulmonary thermodilution was also significant (r (2) = 0.781, p <
      0.0001). There was a bias for the two methods of 0.2 l min(-1), and a precision
      of 2.2 lmin(-1). The GEDV showed no correlation with central venous pressure,
      pulmonary artery occlusion pressure, or RVEDV. CONCLUSION: In patients with
      septic shock, the averaged bias in continuous measurement of cardiac output by
      both a modified pulmonary artery catheter and pulse-contour analysis was small,
      but variability was large. No correlation was found between GEDV and RVEDV. The
      clinical importance of different cardiac filling parameters needs further
      investigation.

PMID- 17549453
TI  - Comment on "Incidence, risk factors and consequences of ICU delirium" by Ouimet
      et al.

PMID- 17549454
TI  - Pediatric Index of Mortality 2 score in Italy: a multicenter, prospective,
      observational study.
AB  - OBJECTIVES: To assess the performance of the Pediatric Index of Mortality (PIM) 2
      score in Italian pediatric intensive care units (PICUs). DESIGN: Prospective,
      observational, multicenter, 1-year study. SETTING: Eighteen medical-surgical
      PICUs. PATIENTS: Consecutive patients (3266) aged 0-16 years admitted between 1
      March 2004 and 28 February 2005. INTERVENTIONS: None. MEASUREMENTS AND MAIN
      RESULTS: To assess the performance of the PIM2 score, discrimination and
      calibration measures were applied to all children admitted to the 18 PICUs, in
      the entire population and in different groups divided for deciles of risk, age
      and admission diagnosis. There was good discrimination, with an area under the
      receiver operating characteristic (ROC) curve of 0.89 (95% CI 0.86-0.91) and good
      calibration of the scoring system [non-significant differences between observed
      and predicted deaths when the population was stratified according to deciles of
      risk (chi2 9.86; 8 df, p = 0.26) for the whole population]. CONCLUSIONS: The PIM2
      score performed well in this sample of the Italian pediatric intensive care
      population. It may need to be reassessed in the injury and postoperative groups
      in larger studies.

PMID- 17549455
TI  - Motoric subtypes of delirium in mechanically ventilated surgical and trauma
      intensive care unit patients.
AB  - OBJECTIVE: Acute brain dysfunction or delirium occurs in the majority of
      mechanically ventilated (MV) medical intensive care unit (ICU) patients and is
      associated with increased mortality. Unfortunately delirium often goes
      undiagnosed as health care providers fail to recognize in particular the
      hypoactive form that is characterized by depressed consciousness without the
      positive symptoms such as agitation. Recently, clinical tools have been developed
      that help to diagnose delirium and determine the subtypes. Their use, however,
      has not been reported in surgical and trauma patients. The objective of this
      study was to identify the prevalence of the motoric subtypes of delirium in
      surgical and trauma ICU patients. METHODS: Adult surgical and trauma ICU patients
      requiring MV longer than 24 h were prospectively evaluated for arousal and
      delirium using well validated instruments. Sedation and delirium were assessed
      using the Richmond Agitation Sedation Scale (RASS) and the Confusion Assessment
      Method in the ICU (CAM-ICU), respectively. Patients were monitored for delirium
      for a maximum of 10[Symbol: see text]days or until ICU discharge. PATIENTS: A
      total of 100 ICU patients (46 surgical and 54 trauma) were enrolled in this
      study. Three patients were excluded from the final analysis because they stayed
      persistently comatose prior to their death. MEASUREMENTS AND RESULTS: Prevalence
      of delirium was 70% for the entire study population with 73% surgical and 67%
      trauma ICU patients having delirium. Evaluation of the subtypes of delirium
      revealed that in surgical and trauma patients, hypoactive delirium (64% and 60%,
      respectively) was significantly more prevalent than the mixed (9% and 6%) and the
      pure hyperactive delirium (0% and 1%). CONCLUSIONS: The prevalence of the
      hypoactive or "quiet" subtype of delirium in surgical and trauma ICU patients
      appears similar to that of previously published data in medical ICU patients. In
      the absence of active monitoring with a validated clinical instrument (CAM-ICU),
      however, this subtype of delirium goes undiagnosed and the prevalence of delirium
      in surgical and trauma ICU patients remains greatly underestimated.

PMID- 17549457
TI  - Prolonged use of carbapenems and colistin predisposes to ventilator-associated
      pneumonia by pandrug-resistant Pseudomonas aeruginosa.
AB  - OBJECTIVE: We present our experience with five cases of pandrug-resistant
      Pseudomonas aeruginosa ventilator-associated pneumonia (VAP) and analysis of risk
      factors. DESIGN AND SETTING: Case-control study in a 15-bed intensive care unit
      (ICU). PATIENTS AND PARTICIPANTS: The study included 5 cases and 20 controls.
      Each case patient was matched to four contemporary controls according to gender,
      prior hospital admissions, hospitalization duration, ICU admission cause, Acute
      Physiology and Chronic Health Evaluation (APACHE) II and Sequential Organ
      Function Assessment (SOFA) scores on ICU admission, and length of ICU stay, and
      mechanical ventilation duration until first VAP episode by a multidrug-resistant
      bacterium. MEASUREMENTS AND RESULTS: Recorded variables included age, gender,
      daily APACHE II and SOFA scores, patient medication, treatment interventions,
      positive cultures and corresponding antibiograms, occurrence of infection,
      sepsis, and septic shock, other ICU-associated morbidity, length of ICU stay and
      mechanical ventilation, and patient outcome. Healthcare worker and environmental
      cultures, and a hand-disinfection survey were performed. Pandrug-resistant P.
      aeruginosa isolates belonged to the same genotype and were bla (VIM-1)-like gene
      positive. The outbreak resolved following reinforcement of infection-control
      measures (September 27). The sole independent predictor for pandrug-resistant P.
      aeruginosa VAP was combined use of carbapenem for more than 20 days and colistin
      use for and more than 13 days (odds ratio 76.0; 95% confidence interval 3.7
      1487.6). An additional risk factor was more than 78 open suctioning procedures
      during 6-26 September (odds ratio 16.0; 95% confidence interval 1.4-185.4).
      CONCLUSIONS: Prolonged carbapenem-colistin use predisposes to VAP by pandrug
      resistant P. aeruginosa. Cross-transmission may be facilitated by open
      suctioning.

PMID- 17549458
TI  - De-escalation therapy rates are significantly higher by bronchoalveolar lavage
      than by tracheal aspirate.
AB  - OBJECTIVE: To assess outcomes with de-escalation therapy in ventilator-associated
      pneumonia (VAP). DESIGN: Prospective observational study. SETTING:
      Multidisciplinary intensive care unit. PATIENTS AND PARTICIPANTS: VAP was
      diagnosed by positive quantitative cultures of both tracheal aspirate and
      bronchoalveolar lavage (BAL) and treated appropriately for all significant
      isolates of tracheal aspirate and BAL in 143 patients who were assigned to de
      escalation therapy by BAL or tracheal aspirate. INTERVENTIONS: None. MEASUREMENTS
      AND RESULTS: Antibiotic therapy was de-escalated in 58 patients (40.5%), who had
      decreased mortality at day 15 (5.1% vs. 31.7%) and day 28 (12% vs. 43.5%) and
      shorter intensive care unit (17.2 +/- 1.2 vs. 22.7 +/- 6.3 days) and hospital
      (23.7 +/- 2.8 vs. 29.8 +/- 11.1 days) stay (p < 0.05). Of the 81 patients
      assigned to tracheal aspirate, the 17 (21%) who achieved de-escalation of therapy
      had reduced 15-day mortality (5.8% vs. 34.3%), reduced 28-day mortality (11.6%
      vs. 45.3%), and shorter intensive care unit (17.2 +/- 1.6 vs. 22.4 +/- 6.4 days)
      and hospital (23.1 +/- 4.4 vs. 29.9 +/- 11.1 days) stay (p < 0.05). Of the 62
      patients assigned to BAL, the 41 (66.1%) who achieved de-escalation of therapy
      had decreased 15-day mortality (4.8% vs. 23.8%), decreased 28-day mortality
      (12.1% vs. 38%), and shorter intensive care unit (17.2 +/- 1.1 vs. 23.2 +/- 6
      days) and hospital (23.8 +/- 2.4 vs. 29.8 +/- 11.4 days) stay (p < 0.05).
      CONCLUSIONS: For patients with VAP who have had appropriate treatment and shown a
      favorable clinical response, mortality and duration of stay can be further
      improved by de-escalation therapy.

PMID- 17549459
TI  - The dosage of small volumes for chromatographic quantifications using a drop-on
      demand dispenser system.
AB  - A commercially available piezo-driven drop-on-demand dispenser was tested for its
      suitability for the preparation of analytical calibration standards and in a
      standard addition approach prior to quantitative ultra performance liquid
      chromatography (UPLC) analysis of homoserines. The reproducibility of the drop-on
      demand dosing system was tested and the verification of the droplet volume was
      performed by preparing a series of 1.0 mg/L caffeine standard solutions from a
      1,000.0 mg/L stock solution and analysis of the concentrations obtained by UPLC.
      The reproducibility was better than 1% relative standard deviation from
      measurement to measurement and the highest was 1.6% from day to day. The results
      were compared with the conventional way of generating standard solutions
      (pipetting). A gravimetric method and a photography-based method for the
      determination of the average single droplet volume were compared and found to be
      in very good agreement. The system was employed for the quantification of N
      decanoyl homoserine by standard addition in bacterial culture supernatants
      containing this analyte. The agreement with conventional quantification
      techniques was high. The paper shows the feasibility of the approach with
      advantages in low sample and solvent volume consumption and very good
      reproducibility and reliability combined with easy usage. Figure Ejected droplet,
      60 mus after application of the pulse.

PMID- 17549460
TI  - Tactile motion aftereffects produced by appropriate presentation for
      mechanoreceptors.
AB  - Tactile motion perception is one of the most important functions for realizing a
      delicate appreciation of the tactile world. To explore the neural dynamics of
      motion processing in the brain, the motion adaptation phenomenon can be a useful
      probe. Tactile motion aftereffects (MAE), however, have not been reported in a
      reproducible fashion, and the indistinctive outcomes of the previous studies can
      be ascribed to the non-optimal choice of adapting and testing stimuli.
      Considering the features of the stimuli used in the studies, the stimuli
      activated the different mechanoreceptors in the adapting and testing phase.
      Consequently, we tested tactile MAE using appropriate combinations of adapting
      and testing stimuli. We used three pins to generate sensation of apparent motion
      on the finger cushion. They were sequentially vibrated with the frequency of 30
      Hz both in adapting and testing phases. It is expected that this procedure
      ensured stimulation for the same mechanoreceptor (Rapid-Adapting mechanoreceptor)
      in both the adaptation and test phases. Using this procedure, we found robust
      tactile MAEs in the various tactile motions such as the short-distance motion
      within the fingertip, the long-distance motion from the finger base to the
      fingertip, and the circular motion on the fingertip. Our development of a
      protocol that reliably produces tactile MAEs will provide a useful psychophysical
      probe into the neural mechanisms of tactile motion processing.

PMID- 17549462
TI  - Changes in the functional MR signal in motor and non-motor areas during
      intermittent fatiguing hand exercise.
AB  - The aim of this study was to determine whether there were significant changes in
      the time course of the functional magnetic resonance imaging (fMRI) signal in
      motor and non-motor regions of both cerebral hemispheres during a unilateral
      fatiguing exercise of the hand. Twelve subjects performed a submaximal (30%)
      intermittent fatiguing handgrip exercise (3 s grip, 2 s release, left hand) for
      approximately 9 min during fMRI scanning. Regression analysis was used to measure
      changes in fMRI signal from primary sensorimotor cortex (SM1), premotor cortex
      and visual cortex (V1) in both hemispheres. Force declined to 77 +/- 3.6% of
      prefatigue maximal force (P < 0.05). The fMRI signal from SM1 contralateral to
      the fatiguing hand increased by 1.2 +/- 0.5% of baseline (P < 0.05). The fMRI
      signal from the ipsilateral SM1 did not change significantly. Premotor cortex
      showed a similar pattern but did not reach significance. The signal from V1
      increased significantly for both hemispheres (contralateral 1.3 +/- 0.9%,
      ipsilateral 1.5 +/- 0.9% of baseline and P < 0.05). During the performance of a
      unimanual, submaximal fatiguing exercise there is an increase in activation of
      motor and non-motor regions. The results are in keeping with the notion of an
      increase in sensory processing and corticomotor drive during fatiguing exercise
      to maintain task performance as fatigue develops.

PMID- 17549461
TI  - Three dimensional kinematics of rapid compensatory eye movements in humans with
      unilateral vestibular deafferentation.
AB  - Saccades executed with the head stationary have kinematics conforming to
      Listing's law (LL), confining the ocular rotational axis to Listing's plane (LP).
      In unilateral vestibular deafferentation (UVD), the vestibulo-ocular reflex
      (VOR), which does not obey LL, has at high head acceleration a slow phase that
      has severely reduced velocity during ipsilesional rotation, and mildly reduced
      velocity during contralesional rotation. Studying four subjects with chronic UVD
      using 3D magnetic search coils, we investigated kinematics of stereotypic rapid
      eye movements that supplement the impaired VOR. We defined LP with the head
      immobile, and expressed eye and head movements as quaternions in LP coordinates.
      Subjects underwent transient whole body yaw at peak acceleration 2,800 degrees
      /s(2) while fixating targets centered, or 20 degrees up or down prior to
      rotation. The VOR shifted ocular torsion out of LP. Vestibular catch-up saccades
      (VCUS) occurred with mean latency 90 +/- 44 ms (SD) from ipsilesional rotation
      onset, maintained initial non-LL torsion so that their quaternion trajectories
      paralleled LP, and had velocity axes changing by half of eye position. During
      contralesional rotation, rapid eye movements occurred at mean latency 135 +/- 36
      ms that were associated with abrupt decelerations (ADs) of the horizontal slow
      phase correcting 3D deviations in its velocity axis, with quaternion trajectories
      not paralleling LP. Rapid eye movements compensating for UVD have two distinct
      kinematics. VCUS have velocity axis dependence on eye position consistent with
      LL, so are probably programmed in 2D by neural circuits subserving visual
      saccades. ADs have kinematics that neither conform to LL nor match the VOR axis,
      but appear instead programmed in 3D to correct VOR axis errors.

PMID- 17549463
TI  - Gaze and smooth pursuit signals interact in parietal area 7m of the behaving
      monkey.
AB  - Posterior parietal cortex is a region specialized for multimodal integration and
      coordinate transformations which converts sensory input to motor output. Eye
      position signals are crucial for such transformations, because they are needed to
      the inner reconstruction of a stable image of the outside world in spite of eye
      movements. Area 7m is a parietal area anatomically connected with oculomotor
      structures such as frontal eye field and superior colliculus. The aim of this
      study was to assess if neurons in area 7m possess activity related to eye
      movements, and if so, which sort of movements are processed. We recorded the
      extracellular activity of 7m neurons in two monkeys trained in both a smooth
      pursuit and a visually guided saccade task. The majority of neurons tested with
      the smooth pursuit task (16/17) showed directional selectivity influenced by the
      eye position. Moreover, these neurons were tuned to inward or outward pursuit
      with respect to the center of extra-personal visual space. About half of the
      cells (11/24) tested with the saccade task changed their activity during the pre
      saccadic period. The majority of neurons presented post-saccadic activity: most
      of the cells showed a directionally-selective phasic response and a modulation by
      eye position during fixation (23/24). Overall, we observed that area 7m contains
      a population of neurons signaling smooth pursuit direction at certain eye
      position and saccade direction toward specific portions of the visual space. We
      hypothesize that area 7m might be involved in spatial map updating which can be
      used for spatial orientation.

PMID- 17549465
TI  - The influence of hospitalisation on drug prescription in primary care--a large
      scale follow-up study.
AB  - OBJECTIVE: To explore the influence of hospitalisation on the prescription of
      drugs in the primary care sector using prescription data of a major statutory
      health insurance (SHI) organisation, with a special focus on the so-called "Me
      Too" drugs - in particular, 3-hydroxy-3-methyl-glutaryl (HMG) CoA reductase
      inhibitors (statins) and proton pump inhibitors (PPIs). METHODS: A comprehensive
      outpatient drug prescription analysis was conducted on members of a SHI who had
      been hospitalised during the first 3 months of 2004. The number and costs of all
      prescriptions of 2426 patients during a 3-month period before admission and after
      discharge, respectively, were compared using Wilcoxon's signed rank test. Data
      are shown in absolute and relative numbers as well as relative risks (RR) and
      their 95% confidence intervals (CIs). RESULTS: The total number of prescriptions
      before hospitalisation and after discharge remained nearly the same, while the
      number of different active substances prescribed per patient decreased by 4%.
      However, overall costs increased after discharge by 15% due to the higher cost
      per prescription. Changes in medication affected nearly every patient (98.1%),
      and 60% had at least five changes. Of the substances prescribed to an individual
      before admission, 57% were cancelled after discharge, and 55% of all substances
      prescribed after discharge were novel prescriptions. Significantly more patients
      received a PPI or statin after hospitalisation (RR for a PPI: 1.27; 95% CI: 1.12 
      1.45; RR for a statin: 1.16; 95% CI: 1.02-1.32). The increase in PPI medication
      was due to a 58% increase in the number of patients receiving pantoprazole, a "Me
      Too" drug. CONCLUSION: Hospitalisation exerts a marked influence on drug therapy
      in ambulatory care, with a significant increase in the prescription of novel, on
      patent drugs instead of less expensive alternatives.

PMID- 17549464
TI  - Leg muscle recruitment during cycling is less developed in triathletes than
      cyclists despite matched cycling training loads.
AB  - Studies of arm movements suggest that interference with motor learning occurs
      when multiple tasks are practiced in sequence or with short interim periods.
      However, interference with learning has only been studied during training periods
      of 1-7 days and it is not known if interference with learning continues during
      long-term multitask training. This study investigated muscle recruitment in
      highly trained triathletes, who swim, cycle and run sequentially during training
      and competition. Comparisons were made to highly trained and novice cyclists,
      i.e. between trained multidiscipline, trained single-discipline and novice single
      discipline athletes, to investigate adaptations of muscle recruitment that occur
      in response to ongoing multitask, or multidiscipline, training. Electromyographic
      (EMG) activity of five leg muscles, tibialis anterior, tibialis posterior,
      peroneus longus, gastrocnemius lateralis and soleus muscles, was recorded during
      cycling using intramuscular fine-wire electrodes. Differences were found between
      trained triathletes and trained cyclists in recruitment of all muscles, and
      patterns of muscle recruitment in trained triathletes were similar to those
      recorded in novice cyclists. More specifically, triathletes and novice cyclists
      were characterised by greater sample variance (i.e. greater variation between
      athletes), greater variation in muscle recruitment patterns between pedal strokes
      for individual cyclists, more extensive and more variable muscle coactivation,
      and less modulation of muscle activity (i.e. greater EMG amplitude between
      primary EMG bursts). In addition, modulation of muscle activity decreased with
      increasing cadence (i.e. the amplitude and duration of muscle activity was
      greater at higher movement speeds) in both triathletes and novice cyclists but
      modulation of muscle activity was not influenced by cadence in trained cyclists.
      Our findings imply that control of muscle recruitment is less developed in
      triathletes than in cyclists matched for cycling training loads, which suggests
      that multidiscipline training may interfere with adaptation of the neuromuscular
      system to cycling training in triathletes.

PMID- 17549466
TI  - Indapamide-induced hyperparathyroidism: a case report.

PMID- 17549467
TI  - Advanced MR imaging in Lhermitte-Duclos disease: moving closer to pathology and
      pathophysiology.
AB  - INTRODUCTION: Lhermitte-Duclos disease (LDD, dysplastic gangliocytoma) is an
      extremely rare cerebellar lesion of uncertain etiology. The debate as to whether
      it constitutes a neoplastic, malformative, or hamartomatous lesion is still
      continuing. In this report we explore the usefulness of susceptibility-weighted
      imaging (SWI), diffusion weighted imaging (DWI), perfusion imaging, and chemical
      shift imaging (CSI) in demonstrating the pathology and pathophysiology in two
      patients with LDD. METHODS: MR imaging of the brain and the cervicodorsal spine
      was performed on a 1.5-T scanner in a 47-year-old woman presenting with numbness
      and paresthesia of both upper and lower limbs, and in a 17-year-old male with
      right frontal headache associated with neck pain. RESULTS: Routine imaging in the
      first patient showed a left-side cerebellar mass with characteristic 'tiger
      striped' thick folia associated with Chiari I malformation, tonsillar herniation
      and cervicodorsal syringomyelia and in the second patient a right cerebellar mass
      with similar findings. The SWI demonstrated the characteristic deep running veins
      between the folia, which is thought to be the cause for vascular contrast
      enhancement. Diffusion showed a T2 shine-through effect with mild increased
      diffusivity, and perfusion showed increase in relative cerebral blood volume,
      relative cerebral blood flow, and mean transit time in the lesion. MR
      spectroscopy demonstrated reduction in metabolites and a prominent lactate peak
      in both the patients. The pathological and pathophysiological significance of
      these findings is discussed. CONCLUSION: MRI with the newer imaging capabilities
      can demonstrate the pathology and pathophysiology in Lhermitte-Duclos disease
      better. SWI helps in detecting the veins around the thickened folia.

PMID- 17549468
TI  - Reproducibility of measurements of hepatic artery and portal vein diameter and
      flow velocity in paediatric liver transplant recipients.
AB  - BACKGROUND: Hepatic blood flow is critical for successful liver transplantation.
      To reliably calculate flow, vessel cross-sectional area and mean flow velocities
      must be reproducibly measurable. OBJECTIVE: To assess the reproducibility of
      sonographic measurements of portal vein (PV) and hepatic artery (HA) diameters
      and mean flow velocities in children after transplantation. MATERIALS AND
      METHODS: Ten children were scanned by two operators 5 or 7 days after
      transplantation. Each scanned the same patient twice measuring the diameter and
      the time-averaged velocity (TAV) in the PV and HA. Operators were blinded to all
      measurements. Agreement and repeatability were analysed statistically. RESULTS:
      The interobserver variation in PV and HA diameters and TAVs were expressed as
      mean differences between operators and plotted against the mean value for each.
      This showed relatively poor agreement for PV diameter (mean difference 1.23 +/-
      0.96 mm), but better agreement for HA diameter (mean difference 0.18 +/- 0.6 mm).
      Intraobserver differences were of similar magnitude. TAVs showed better agreement
      and repeatability. CONCLUSION: This study demonstrates substantial inter- and
      intraobserver variation in sonographic measurements of vessel diameters and TAV
      after paediatric liver transplantation. Estimates of volume of blood flow to the
      transplant derived from these measurements are poorly reproducible.

PMID- 17549469
TI  - Kinetics of the electron transfer reaction of Cytochrome c (552) adsorbed on
      biomimetic electrode studied by time-resolved surface-enhanced resonance Raman
      spectroscopy and electrochemistry.
AB  - Cytochrome c (552) (Cyt-c (552)) and its redox partner ba ( 3 )-oxidase from
      Thermus thermophilus possess structural differences compared with Horse heart
      cytochrome c (cyt-c)/cytochrome c oxidase (CcO) system, where the recognition
      between partners and the electron transfer (ET) process is initiated via
      electrostatic interactions. We demonstrated in a previous study by surface
      enhanced resonance Raman (SERR) spectroscopy that roughened silver electrodes
      coated with uncharged mixed self-assembled monolayers HS-(CH(2))( n )-CH(3)/HS
      (CH(2))( n + 1)-OH 50/50, n = 5, 10 or 15, was a good model to mimic the Cyt-c
      (552) redox partner. All the adsorbed molecules are well oriented on such
      biomimetic electrodes and transfer one electron during the redox process. The
      present work focuses on the kinetic part of the heterogeneous ET process of Cyt-c
      (552) adsorbed onto electrodes coated with such mixed SAMs of different alkyl
      chain length. For that purpose, two complementary methods were combined. Firstly
      cyclic voltammetry shows that the ET between the adsorbed Cyt-c (552) and the
      biomimetic electrode is direct and reversible. Furthermore, it allows the
      estimation of both the density surface coverage of adsorbed Cyt-c (552) and the
      kinetic constants values. Secondly, time-resolved SERR (TR-SERR) spectroscopy
      showed that the ET process occurs without conformational change of the Cyt-c
      (552) heme group and allows the determination of kinetic constants. Results show
      that the kinetic constant values obtained by TR-SERR spectroscopy could be
      compared to those obtained from cyclic voltammetry. They are estimated at 200,
      150 and 40 s(-1) for the ET of Cyt-c (552) adsorbed onto electrodes coated with
      mixed SAMs HS-(CH(2))( n )-CH(3)/HS-(CH(2))( n + 1)-OH 50/50, n = 5, 10 or 15,
      respectively.

PMID- 17549470
TI  - Screening of high-yielding biocontrol bacterium Bs-916 mutant by ion
      implantation.
AB  - Bacillus subtilis 916 was an effective biocontrol agent in control rice sheath
      blight caused by Rhizoctonia solani. To further improve its antagonistic ability,
      low-energy ion implantation was applied in Bs-916. We studied the effects of
      different doses of N(+) implantation. The optimum dose of ion implantation for
      the Bs-916 was from 15 x 2.6 x 10(14) N(+)/cm(2) to 25 x 2.6 x 10(14) N(+)/cm(2).
      The mutant strain designated as Bs-H74 was obtained, which showed higher
      inhibition activity in the screening plate. Its inhibition zone against the
      indicator organism increased by 30.7% compared to the parental strain. The
      control effect of rice sheath blight was improved by 14.6% over that of Bs-916.
      Thin-layer chromatography and high-performance liquid chromatography analysis
      indicated that lipopeptides produced by Bs-916 and the mutant strains belonged to
      the surfactin family. Bs-H74 produced approximately 3.0-fold surfactin compared
      to that of Bs-916. To determine the role of surfactin in biocontrol by Bs-916, we
      tested another mutant strain, Bs-M49, which produced lower levels of surfactin
      significantly, and found that Bs-M49 had no obvious effects against R. solani.
      These results suggested that the surfactin produced by Bs-916 plays an important
      role in the suppression of sheath blight. These observations also showed that the
      Bs-H74 mutant strain is a better biocontrol agent than the parental strain.

PMID- 17549471
TI  - Production in Trichoderma reesei of three xylanases from Chaetomium thermophilum:
      a recombinant thermoxylanase for biobleaching of kraft pulp.
AB  - Three endoxylanase genes were cloned from the thermophilic fungus Chaetomium
      thermophilum CBS 730.95. All genes contained the typical consensus sequence of
      family 11 glycoside hydrolases. Genomic copies of Ct xyn11A, Ct xyn11B, and Ct
      xyn11C were expressed in the filamentous fungus T. reesei under the control of
      the strong T. reesei cel7A (cellobiohydrolase 1, cbh1) promoter. The molecular
      masses of the Ct Xyn11A, Ct Xyn11B, and Ct Xyn11C proteins on sodium dodecyl
      sulfate polyacrylamide gel electrophoresis (SDS-PAGE) were 27, 23, and 22 kDa,
      respectively. Ct Xyn11A was produced almost as efficiently as the homologous
      xylanase II from a corresponding single-copy transformant strain. Ct Xyn11B
      production level was approximately half of that of Ct Xyn11A. The amount of Ct
      Xyn11C was remarkably lower. Ct Xyn11A had the highest temperature optimum and
      stability of the recombinant xylanases and the highest activity at acid-neutral
      pH (pH 5-7). It was the most suitable for industrial bleaching of kraft pulp at
      high temperature.

PMID- 17549472
TI  - Long-term follow-up of patients treated by adoptive transfer of melanoma tumor
      infiltrating lymphocytes as adjuvant therapy for stage III melanoma.
AB  - The first analysis of our clinical trial on interest of using tumor-infiltrating
      lymphocytes (TIL) as adjuvant therapy for stage III (regional lymph nodes)
      melanoma was published in 2002 [5]. The aim of this paper is to update clinical
      results of 7 years of follow-up after the last treated patient. In the trial
      conducted between December 1993 and January 1999, patients without any detectable
      metastases after lymph node excision were randomly assigned to receive either TIL
      plus interleukin-2 (IL-2) for 2 months, or IL-2 only. The duration of the relapse
      free interval was the primary objective. Eighty-eight patients were enrolled in
      the study. Currently, the last analysis performed in June 2006, after a median
      follow-up of 114.8 months, did not show change of non-significant extension of
      the relapse-free interval or overall survival. However, this second analysis
      strengthens our first hypothesis about the relationship between number of invaded
      lymph nodes and TIL treatment effectiveness. In the group with only one invaded
      lymph node, the estimated relapse rate was significantly lower (P (adjusted) =
      0.0219) and the overall survival was increased (P (adjusted) = 0.0125) in the
      TIL+IL-2 arm compared with the IL-2 only arm. No differences between the two
      arms, either with regard to the duration of disease-free survival (P (adjusted) =
      0.38) or overall survival (P (adjusted) = 0.43), were noted in the group with
      more than one invaded lymph node, whatever the number of invaded lymph nodes.
      Treatment was compatible with normal daily activity. This study, with a very long
      follow up (median of almost 10 years), postulates for the first time relationship
      between TIL efficiency in stage III melanoma (AJCC) and number of invaded lymph
      nodes, indicating that tumor burden might be a crucial factor in the production
      of an effective in vitro expansion of T cells specific for autologous tumor
      antigen, a finding which could be of value in future vaccine development for the
      treatment of melanoma.

PMID- 17549473
TI  - Robust anti-tumor immunity and memory in Rag-1-deficient mice following adoptive
      transfer of cytokine-primed splenocytes and tumor CD80 expression.
AB  - Successful immunotherapy of solid tumors has proven difficult to achieve. The aim
      of the current study was to further investigate the effects of peripheral CD80
      mediated co-stimulation on the efficacy of polyclonal anti-tumor effector CTL in
      an adoptive transfer model. Splenocytes obtained from wild-type mice immunized
      with CD80-transduced EL4 tumor cells were expanded in vitro in the presence of
      either IL-12 or IL-15 and irradiated CD80-transduced EL4 tumor cells. Polyclonal
      CD8 T cells were the major subset in the effector population. Primed effector
      cells were adoptively transferred into immuno-deficient Rag-1-deficient mice
      which were then challenged with syngeneic vector-control or CD80-transduced EL4
      tumor cells. Expression of CD80 enhanced the elimination of EL4 tumors and mouse
      survival. Both IL-12 and IL-15 cultured cells had enhanced cytotoxicity.
      Importantly, anti-tumor memory was maintained without tumor evasion following re
      challenge with either CD80-transduced and vector-control EL4 cells. We also show,
      using antibody-mediated depletion, that endogenous NK cells present in Rag-1
      deficient mice exert anti-EL4 tumor activity that is enhanced by CD80 expression.
      Collectively these data show that peripheral co-stimulation by tumor expression
      of CD80 results in enhanced anti-tumor efficacy of NK and polyclonal effector T
      cells, and suggest that TCR repertoire diversity helps protect against tumor
      escape and provides memory with resultant robust immunity to subsequent tumor
      challenge irrespective of CD80 status.

PMID- 17549474
TI  - Interferon-gamma attenuates the survival activity of G-CSF through PI3K/Akt
      signaling pathway in mouse multipotent progenitor cells.
AB  - Apoptosis plays an important role in the injury to stem and progenitor
      compartments associated with aberrant interferon-gamma (IFN-gamma) in aplastic
      anemia (AA), which is characterized by the loss of stem cells; however, its
      molecular mechanism is poorly understood. In this study, we have addressed the
      mechanism of the apoptotic function of IFN-gamma against hematopoietic stem
      and/or progenitors. Although granulocyte colony-stimulating factor (G-CSF)
      augmented survival and proliferative and differentiating activity in 32D cells,
      mouse multipotent progenitor cells, these effects were abolished by IFN-gamma and
      were susceptible to apoptosis with IFN-gamma. IFN-gamma attenuated Akt
      phosphorylated by G-CSF in a dose- and time-dependent manner. Wortmannin, a
      specific inhibitor of phosphatidylinositol 3-kinase (PI3K), enhanced the
      inhibitory effect on Akt phosphorylated by G-CSF in collaboration with IFN-gamma,
      suggesting that the activity of IFN-gamma might converge on the PI3K pathway. We
      examined the expression of Bcl-2-associated death (Bad), which works downstream
      of Akt. IFN-gamma increased the Bad protein reduced by G-CSF. IFN-gamma induced
      apoptosis in 32D cells through the caspase pathway. Taken together, these results
      suggest that IFN-gamma could exert inhibitory action on stem cells and/or
      progenitors by interference with the PI3K/Akt signaling pathway. Our findings may
      contribute to understanding the decreased number of stem cells characteristic of
      AA.

PMID- 17549475
TI  - An open-label study to evaluate dose and cycle dependence of the pharmacokinetics
      of pegylated liposomal doxorubicin.
AB  - PURPOSE: There are no definitive data in humans on the dose dependence and/or
      cycle dependence of the pharmacokinetics (PK) of pegylated liposomal doxorubicin
      (PLD). This study examined the PK of PLD across a twofold dose variation and
      along 3 cycles. METHODS: Fifteen patients received PLD in successive doses of 60,
      30, and 45 mg/m(2) (Arm A) and 30, 60, and 45 mg/m(2) (Arm B), every 4 weeks.
      Twelve patients, six on each arm, completed all three cycles and were fully
      evaluable. Plasma levels of doxorubicin were analyzed by HPLC and fluorimetry. PK
      analysis was done by non-compartmental method. Repeated measures ANOVA and paired
      tests were used for statistical analysis. RESULTS: There was no significant
      difference in the PK parameters examined when the dose was increased from 30 to
      60 mg/m(2). However, when we analyzed the effect of cycle number on the PK, we
      found a gradual and significant inhibition of clearance (P < 0.0001) from the 1st
      through the 3rd cycle of PLD, with a geometric mean increase of 43% in dose
      normalized AUC (P = 0.0003). Dose-normalized C(max) and T(1/2) mean values
      increased by 17 and 18%, respectively between the 1st and 3rd cycles, but only
      the increase in T(1/2) was statistically significant (P = 0.0017). CONCLUSIONS:
      While the PK of PLD is not dose-dependent within the dose range of 30-60 mg/m(2),
      there is evidence of a cycle-dependent effect that results in inhibition of
      clearance when patients receive successive cycles of PLD. These results suggest
      the need for dose adjustments of PLD upon retreatment to minimize the risk of
      toxicity.

PMID- 17549476
TI  - Pharmacokinetics and safety of bevacizumab administered in combination with
      cisplatin and paclitaxel in cynomolgus monkeys.
AB  - PURPOSE: Bevacizumab is the first anti-angiogenic monoclonal antibody approved
      for use in combination with chemotherapy for treatment of a variety of solid
      tumors. The objective of this study was to evaluate the safety of bevacizumab
      when administered concomitantly with paclitaxel and cisplatin to cynomolgus
      monkeys, and to assess the pharmacokinetic and safety interactions between
      bevacizumab and the two chemotherapeutic agents. METHODS: Twenty male cynomolgus
      monkeys (Macaca fasicularis) were randomized to one of four treatment groups:
      vehicle, bevacizumab alone, cisplatin alone, and the combination of cisplatin and
      bevacizumab. Blood collection over serial time points allowed determination of
      the pharmacokinetic parameters of paclitaxel and bevacizumab and the maximum
      concentration (C (max)) for cisplatin. Drug concentrations were determined by
      graphite-furnace atomic absorption, high performance liquid chromatography, and
      enzyme-linked immunosorbent assay methods, for cisplatin, paclitaxel, and
      bevacizumab, respectively. RESULTS: AUC0-t values for bevacizumab when
      administered alone or in combination with chemotherapy were 6,747 +/- 1,872 and
      7,366 +/- 1,599 microg/ml x day, respectively. AUC0-t values for paclitaxel with
      or without concomitantly administered bevacizumab were 10.9 +/- 2.9 and 10.3 +/-
      3.7 microg/ml x day, respectively. No alterations in the C (max) of bevacizumab,
      paclitaxel, or cisplatin were observed between any of the treatment groups. As
      expected, based on their known safety profile, the administration of cisplatin
      and paclitaxel were associated with vomiting, decreased body weight, and
      transient decreases in white blood cell and absolute neutrophil counts;
      concomitant bevacizumab administration did not alter the incidence or severity of
      these toxicological effects. CONCLUSION: Pharmacokinetic estimates for
      bevacizumab, paclitaxel and cisplatin indicate that combination of bevacizumab
      with the two chemotherapeutic agents does not result in a pharmacokinetic
      interaction. Moreover, the addition of bevacizumab to the chemotherapy regimen
      did not appear to alter the safety profiles of cisplatin/paclitaxel in cynomolgus
      monkeys. Results from the present study supported the clinical development of
      bevacizumab treatment regimens in combination with the chemotherapeutic agents
      paclitaxel and cisplatin.

PMID- 17549477
TI  - Involvement of UDP-glucuronosyltransferase activity in irinotecan-induced delayed
      onset diarrhea in rats.
AB  - We assessed the involvement of UDP-glucuronosyltransferase (UGT) activity in
      episodes of irinotecan hydrochloride (CPT-11)-induced delayed-onset diarrhea
      using a mutant rat strain with an inherited deficiency of UGT1A (Gunn rats). Gunn
      rats exhibited severe diarrhea after the intravenous administration of CPT-11 at
      a dose of 20 mg/kg, whereas Wistar rats did not. In the epithelium of the small
      intestine and cecum in Gunn rats, the shortening of villi, degeneration of
      crypts, and destruction of the nucleus were observed. The AUC, MRT, and t (1/2)
      of CPT-11, and the AUC of 7-ethyl-10-hydroxycamptothecin (SN-38) in plasma were,
      respectively, 1.6-fold, 1.5-fold, 1.7-fold, and 6.5-fold higher, and the
      cumulative biliary excretion rate of SN-38 was 2.3-fold higher, in Gunn rats than
      Wistar rats. SN-38 glucuronide excreted via bile in Wistar rats was not de
      conjugated in the small intestinal lumen. The SN-38 AUC values in small
      intestinal tissues were also 5.0 to 5.8-fold higher in Gunn rats than Wistar
      rats. In conclusion, Gunn rats developed severe delayed-onset diarrhea after i.v.
      administration of CPT-11 at a much lower dose. Severe intestinal impairments
      would be induced in Gunn rats through exposure to SN-38 at high levels for a long
      period mainly via the intestinal lumen and partially via the bloodstream. These
      results clarified that the deficiency of UGT activity contributed greatly to the
      induction of the CPT-11-induced delayed-onset diarrhea and epithelial impairment
      in the intestine. In the clinic, great care is needed when using chemotherapy
      with CPT-11 in patients with poor UGT activity.

PMID- 17549478
TI  - PDGFRalpha/FIP1L1-positive chronic eosinophilic leukemia presenting with retro
      orbital localization: efficacy of imatinib treatment.
AB  - INTRODUCTION: The fusion protein between the platelet-derived growth factor
      receptor alpha (PDGFRalpha, P) gene and the Fip1-like1 (FIP1L1, F) may be
      identified in 14 to 60% of HES and it indicates a clonal hypereosinophilic
      syndrome called F/P-positive CEL. We herein report a case of F/P-positive CEL
      with retro-orbital localization, who was successfully treated with imatinib. CASE
      REPORT: A 53-year-old male presented an absolute eosinophil count of
      25,000/mm(3), anemia (Hb 10.2 g/dl) and a moderate increase in the platelet count
      (571,000/mm(3)). A clinical examination revealed left exophthalm, associated with
      diffuse hypoesthesia and diplopia. A CT scan of orbits showed a lesion located in
      the lachrymal fossa of the left orbit with intra- and extra-conical extension.
      Molecular analysis excluded the presence of bcr/abl transcript while a F/P fusion
      tyrosine kinase signal was documented. Imatinib mesylate (IM) was started and,
      after 7 days of treatment eosinophil count significantly declined along with a
      dramatic reduction of the left exophthalm. IM dosage was increased up to 300
      mg/day. The drug was well tolerated with an initial modest haematological
      toxicity. The left exophthalm, as well as hypoesthesia and diplopia, disappeared
      after IM therapy. MRI showed a clear reduction of the intra- and extra-conical
      growth process. BM molecular signal of the F/P fusion gene resulted undetectable
      after 4 weeks of treatment. CONCLUSION: In our case, the diagnosis of FIPIL1
      PDGFRA-positive CEL and IM therapy has allowed the patient to experience an
      excellent clinical therapeutic result, avoiding surgical treatment of the retro
      orbital mass.

PMID- 17549479
TI  - Phase II study of gemcitabine and carboplatin in patients with advanced non-small
      cell lung cancer.
AB  - PURPOSE: To evaluate the efficacy and safety of gemcitabine in combination with
      carboplatin at standard rate or fixed dose rate infusion in patients with
      advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: In this
      prospective study, patients with chemonaive advanced NSCLC were randomized to
      receive gemcitabine at a standard rate (gemcitabine 1,200 mg/m2 over 30 min, the
      standard arm) or a fixed dose rate (gemcitabine 1,200 mg/m2 over 120 min, the FDR
      arm) on days 1 and 8 every 3 week cycle. In both treatment arms, carboplatin at
      AUC of 5 was administered over 4 h following gemcitabine on day 1 of each cycle.
      RESULTS: From November 2003 to June 2005, a total of 42 patients, in which 7
      (17%) patients had stage III(B) disease and 35 (83%) had stage IV disease, were
      enrolled into this study. All patients were included in efficacy and toxicity
      assessment. No patient had a complete response. Seven (33%) patients in the
      standard arm and 10 (48%) in the FDR arm had a partial response. The median time
      to progression and median overall survival time in the standard arm was 5.4
      months (95% CI, 3.8-7 months) and 11.5 months (95% CI, 8.2-14.8 months),
      respectively, while in the FDR arm was 6.5 (95% CI, 4.4-8.6 months) months, 12.0
      months (95% CI, 11.3-12.7 months), respectively. The most frequently reported
      grade 3 or 4 hematological toxicities were thrombocytopenia (38% patients in the
      standard arm and 43% in the FDR arm) and neutropenia (24% in the standard arm and
      33% in the FDR arm). Although hematological toxicity occurred in a little higher
      percent of patients in the FDR arm than in the standard arm, there were no
      discernible differences by statistical analysis in both treatment arms (P >
      0.05). And significant nonhematologic toxicities were infrequent and tolerable in
      both arms. No significant difference existed also (P > 0.05). CONCLUSION: In this
      phase II study, gemcitabine in combination with carboplatin either at standard
      rate or fixed dose rate infusion was clinically effective and well tolerated in
      patients with advanced NSCLC.

PMID- 17549480
TI  - Effect of cortisol on cell proliferation and the expression of lipoprotein lipase
      and vascular endothelial growth factor in a human osteosarcoma cell line.
AB  - PURPOSE: The aim of this study is to investigate whether cortisol inhibited cell
      proliferation and the expressions of lipoprotein lipase (LPL), a key enzyme
      involved in the energy metabolism in tumor cells, and vascular endothelial growth
      factor (VEGF), a potent angiogenic factor in the tumor, in cultures of OST cells,
      a human osteosarcoma cell line. METHODS: OST cells were treated for 48 h with or
      without cortisol. To examine the effect of cortisol on cell proliferation, the
      expression of proliferating cell nuclear antigen (PCNA) was examined by Western
      blotting, and the amount of (3)H-thymidine incorporated into DNA during the last
      30 min of the 48-h treatment period was measured. To examine the effect of
      cortisol on the expression of LPL, the activity and mass of LPL were measured in
      the extract of acetone/ether powder of cells, and the amount of (35)S-methionine
      incorporated into LPL during the last 2 h of the 48-h treatment period was
      measured by immunoprecipitation. The expression of VEGF was examined by
      immunohistochemistry and Western blotting. RESULTS: The amount of (3)H-thymidine
      incorporated into DNA and the level of PCNA were lower in the cortisol-treated
      cultures than in the untreated cultures, thus indicating that cortisol inhibited
      the proliferation of OST cells. The synthetic rate and activity of LPL were lower
      in the cortisol-treated cultures than in the untreated cultures but no difference
      in the specific activity of LPL between the two cultures was observed, thus
      indicating that cortisol inhibited LPL synthesis, thereby resulting in a
      decreased LPL activity. The expression of VEGF was lower in the cortisol-treated
      cultures than in the untreated cultures. CONCLUSION: Cortisol not only has the
      ability to inhibit cell proliferation but also the ability to inhibit the
      expressions of LPL and VEGF in cultures of OST cells.

PMID- 17549481
TI  - Criterion for stable reentry in a ring of cardiac tissue.
AB  - We model electrical wave propagation in a ring of cardiac tissue using an mth
      order difference equation, where m denotes the number of cells in the ring. Under
      physiologically reasonable assumptions, the difference equation has a unique
      equilibrium solution. Applying Jury's stability test, we prove a theorem
      concerning the local asymptotic stability of this equilibrium solution. Our
      results yield conditions for sustained reentrant tachycardia, a type of cardiac
      arrhythmia.

PMID- 17549482
TI  - Pro-inflammatory cellular immune response in Behcet's disease.
AB  - Several proteins are investigated as candidate auto-antigens in the pathogenesis
      of Behcet's disease (BD). This study aimed to screen the cellular responses to
      auto-antigen (alphaB-crystallin, alphaBC), and microorganism (Streptococcus
      sangius KTH-1 BES-1 protein) derived peptides as well as to isopentenyl
      pyrophosphate (IPP). Peripheral blood mononuclear cells (PBMC) from 22 BD
      patients and 22 healthy controls (HC) were stimulated in vitro with alphaBC, BES
      1 peptides, IPP and PPD and induced proliferation as well as the secreted
      interleukin (IL)-12 and interferon (IFN)-gamma production levels were measured.
      We did not observe any significant difference in cellular proliferation between
      BD patients and HC. Induction of IL-12 secretion with alphaBC was stronger in BD
      patients (P = 0.04) and in the disease subgroup with uveitis (P = 0.027) compared
      the HC. When responses to PPD were compared, proliferation of PMBC was lower (P =
      0.03), whereas IL-12 secretion was higher in BD (P = 0.04) as well as in patients
      under colchicum treatment (P = 0.04) and with vascular involvement (P = 0.006)
      compared to HC. BES-1(373-385 )peptide induced also higher IL-12 productions by
      PBMC of BD patients (P = 0.017) and of patients with uveitis (P = 0.013).
      Finally, IPP stimulated higher IL-12 secretions from PBMC in BD patients (P =
      0.035) and in patients with (P = 0.02) or without (P = 0.017) uveitis or
      arthritis (P = 0.04), under colchicum treatment (P = 0.01) or not receiving any
      immunosuppressive treatment (P = 0.007) compared to HC. These results suggest a
      more prominent pro-inflammatory cytokine secretion from PBMC in BD patients
      compared to HC in response to various antigens including alphaBC protein, BES
      1(373-385), IPP and PPD.

PMID- 17549483
TI  - Perfusion CT in acute stroke: prediction of vessel recanalization and clinical
      outcome in intravenous thrombolytic therapy.
AB  - This study evaluated perfusion computed tomography (PCT) for the prediction of
      vessel recanalization and clinical outcome in patients undergoing intravenous
      thrombolysis. Thirty-nine patients with acute ischemic stroke of the middle
      cerebral artery territory underwent intravenous thrombolysis within 3 h of
      symptom onset. They all had non-enhanced CT (NECT), PCT, and CT angiography (CTA)
      before treatment. The Alberta Stroke Program Early Computed Tomography (ASPECT)
      score was applied to NECT and PCT maps to assess the extent of ischemia. CTA was
      assessed for the site of vessel occlusion. The National Institute of Health
      Stroke Scale (NIHSS) score was used for initial clinical assessment. Three-month
      clinical outcome was assessed using the modified Rankin scale. Vessel
      recanalization was determined by follow-up ultrasound. Of the PCT maps, a
      cerebral blood volume (CBV) ASPECT score of >6 versus < or =6 was the best
      predictor for clinical outcome (odds ratio, 31.43; 95% confidence interval, 3.41
      289.58; P < 0.002), and was superior to NIHSS, NECT and CTA. No significant
      differences in ASPECT scores were found for the prediction of vessel
      recanalization. ASPECT score applied to PCT maps in acute stroke patients
      predicts the clinical outcome of intravenous thrombolysis and is superior to both
      early NECT and clinical parameters.

PMID- 17549484
TI  - Re-evaluation of pheochromocytomas on delayed contrast-enhanced CT: washout
      enhancement and other imaging features.
AB  - The purpose of this study was to retrospectively evaluate the enhancement washout
      and other imaging features of pheochromocytomas on delayed contrast-enhanced CT.
      Twenty-four patients with 31 pathologically confirmed pheochromocytomas were
      examined using unenhanced, early and delayed contrast-enhanced CT. The range of
      their APEW (absolute percentage of enhancement washout) or RPEW (relative PEW)
      values was analyzed. The other CT features including cystic or necrotic change,
      calcification, and hemorrhage were also determined by a pathologic correlation.
      Of the 31 pheochromocytomas, 10 (32%) had APEW values of 60% or less and RPEW
      values of 40% or less. Fourteen (45%) had APEW values >60% and RPEW values >40%.
      CT showed cystic or necrotic changes in 11 pheochromocytomas (35%) and
      calcification (10%) in 3. Nineteen pheochromocytomas showed cystic or necrotic
      changes on early contrast-enhanced CT, but eight of these lesions showed late
      enhancement on delayed contrast-enhanced CT, which pathologically corresponded to
      myxoid degeneration. The unenhanced CT showed hemorrhage in 23 pheochromocytomas,
      but the pathology examinations showed hemorrhage in 15 lesions. Many
      pheochromocytomas can be misdiagnosed as adenomas on CT due to the high
      enhancement washout values. Delayed contrast-enhanced CT can detect myxoid
      degeneration with late enhancement, which is seen as a cystic or necrotic change
      on early contrast-enhanced CT.

PMID- 17549485
TI  - Liver, bone marrow, pancreas and pituitary gland iron overload in young and adult
      thalassemic patients: a T2 relaxometry study.
AB  - Thirty-seven patients with beta-thalassemia major, including 14 adolescents (15.2
      +/- 3.0 years) and 23 adults (26.4 +/- 6.9 years), were studied. T2 relaxation
      time (T2) of the liver, bone marrow, pancreas and pituitary gland was measured in
      a 1.5-Tesla magnetic resonance (MR) imager, using a multiecho spin-echo sequence
      (TR/TE 2,000/20, 40, 60, 80, 100, 120, 140, 160 ms). Pituitary gland height was
      evaluated in a midline sagittal scan of a spin-echo sequence (TR/TE, 500/20 ms).
      The T2 of the pituitary gland was higher in adolescents (59.4 +/- 15 ms) than in
      adults (45.3 +/- 10.4 ms), P < 0.05. The T2 of the pancreas was lower in
      adolescents (43.6 +/- 10.3 ms) than in adults (54.4 +/- 10.4 ms). No difference
      among groups was found in the T2 of the liver and bone marrow. There was no
      significant correlation of the T2 among the liver, pancreas, pituitary gland and
      bone marrow. There was no significant correlation between serum ferritin and T2
      of the liver, pancreas and bone marrow. Pituitary T2 showed a significant
      correlation with pituitary gland height (adolescents: R = 0.63, adults: R = 0.62,
      P < 0.05) and serum ferritin (adolescents: R = -0.60, adults: R = -0.50, P <
      0.05). In conclusion, iron overload evaluated by T2 is organ specific. After
      adolescence, age-related T2 changes are predominantly associated with pituitary
      siderosis and fatty degeneration of the pancreas. Pituitary size decreases with
      progressing siderosis.

PMID- 17549486
TI  - Functional cine MRI of the abdomen for the assessment of implanted synthetic mesh
      in patients after incisional hernia repair: initial results.
AB  - The aim of our study was to develop a method that allows the visualisation and
      evaluation of implanted mesh in patients after incisional hernia repair with MRI.
      Furthermore, we assessed problems typically related with mesh implantation like
      adhesions and muscular atrophy. We enrolled 28 patients after incisional hernia
      repair. In 10 patients mesh implantation was done by laparoscopy (expanded
      polytetrafluoroethylene=ePTFE mesh) and in 18 by laparotomy (polypropylene mesh).
      Functional MRI was performed on a 1.5-T system in supine position. Sagittal and
      axial TrueFISP images of the entire abdomen were acquired with the patient
      repeatedly straining. Evaluation included: correct position and intact fixation
      of the mesh, furthermore visceral adhesions, recurrent hernia and atrophy of the
      rectus muscle. The ePTFE mesh was visible in all cases; the polypropylene mesh
      was not detectable. In seven of the ten ePTFE meshes the fixation was not intact;
      two recurrent hernias were detected. Twenty of 28 patients had intraabdominal
      adhesions. In 5 cases mobility of the abdominal wall was reduced, and 16 patients
      showed an atropy of the rectus muscle. Functional cine MRI is a suitable method
      for follow-up studies in patients after hernia repair. ePTFE meshes can be
      visualized directly, and typical complications like intestinal adhesions and
      abdominal wall dysmotility can be assessed reliably.

PMID- 17549487
TI  - Use of multidetector computed tomography for the assessment of acute chest pain:
      a consensus statement of the North American Society of Cardiac Imaging and the
      European Society of Cardiac Radiology.

PMID- 17549488
TI  - Usefulness of 40-slice multidetector row computed tomography to detect coronary
      disease in patients prior to cardiac valve surgery.
AB  - Preoperative identification of significant coronary artery disease (CAD) in
      patients prior to valve surgery requires systematic invasive coronary
      angiography. The purpose of this current prospective study was to evaluate
      whether exclusion of CAD by multi-detector CT (MDCT) might potentially avoid
      systematic cardiac catheterization in these patients. Eighty-two patients (53
      males, 62 +/- 13 years) scheduled to undergo valve surgery underwent 40-slice
      MDCT before invasive quantitative coronary angiography (QCA). According to QCA,
      15 patients had CAD (5 one-vessel, 6 two-vessel and 4 three-vessel disease). The
      remaining 67 patients had no CAD. On a per-vessel basis, MDCT correctly
      identified 27/29 (sensitivity 93%) vessels with and excluded 277/299 vessels
      (specificity 93%) without CAD. On a per-patient basis, MDCT correctly identified
      14/15 patients with (sensitivity 93%) and 60/67 patients without CAD (specificity
      90%). Positive and negative predictive values of MDCT were 67% and 98%.
      Performing invasive angiography only in patients with abnormal MDCT might have
      avoided QCA in 60/82 (73%). MDCT could be potentially useful in the preoperative
      evaluation of patients with valve disease. By selecting only those patients with
      coronary lesions to undergo invasive coronary angiography, it could avoid cardiac
      catheterization in a large number of patients without CAD.

PMID- 17549489
TI  - Assessment of functional anatomy of the mitral valve in patients with mitral
      regurgitation with cine magnetic resonance imaging: comparison with
      transesophageal echocardiography and surgical results.
AB  - The ability of magnetic resonance imaging (MRI) to accurately define the
      functional anatomy of mitral regurgitation was assessed. Transesophageal
      echocardiography (TEE) and cine MRI were performed on 43 patients with mitral
      regurgitation and were compared for the jet number, location, direction and
      presence of a prolapse (atrial displacement, malapposition or a flail). In 36
      patients, diagnostic accuracy in reference to surgery was assessed. Comparing TEE
      and MRI the jet number and location were judged in concordance in 86% of
      patients. Jet location did not show a significant difference (Wilcoxon: P = 0.66)
      and both modalities correlated strongly (Spearman: r = 0.68, P<0.0001). Jet
      direction was judged with high concordance (kappa=0.63). Additionally, prolapse
      evaluation showed high concordance (kappa: valve, 0.63; anterior mitral leaflet,
      0.70; posterior mitral leaflet, 0.73). Compared with surgery, the sensitivity for
      the detection of malapposition of any leaflet or one of both leaflets ranged
      between 75% and 93% for TEE and 71% and 89% for MRI. Specificities ranged between
      88 and 96% for TEE and 88 and 100% for MRI. TEE detected torn chordae in all ten
      patients, six of which were missed by MRI. MRI is comparable with TEE in prolapse
      and jet evaluation. MRI is inferior to TEE in depicting anatomical details such
      as torn chordae.

PMID- 17549490
TI  - Feasibility study of computed tomography colonography using limited bowel
      preparation at normal and low-dose levels study.
AB  - The purpose was to evaluate low-dose CT colonography without cathartic cleansing
      in terms of image quality, polyp visualization and patient acceptance. Sixty-one
      patients scheduled for colonoscopy started a low-fiber diet, lactulose and
      amidotrizoic-acid for fecal tagging 2 days prior to the CT scan (standard dose,
      5.8-8.2 mSv). The original raw data of 51 patients were modified and
      reconstructed at simulated 2.3 and 0.7 mSv levels. Two observers evaluated the
      standard dose scan regarding image quality and polyps. A third evaluated the
      presence of polyps at all three mSv levels in a blinded prospective way. All
      observers were blinded to the reference standard: colonoscopy. At three times
      patients were given questionnaires relating to their experiences and preference.
      Image quality was sufficient in all patients, but significantly lower in the
      cecum, sigmoid and rectum. The two observers correctly identified respectively
      10/15 (67%) and 9/15 (60%) polyps > or =10 mm, with 5 and 8 false-positive
      lesions (standard dose scan). Dose reduction down to 0.7 mSv was not associated
      with significant changes in diagnostic value (polyps > or =10 mm). Eighty percent
      of patients preferred CT colonography and 13% preferred colonoscopy (P<0.001). CT
      colonography without cleansing is preferred to colonoscopy and shows sufficient
      image quality and moderate sensitivity, without impaired diagnostic value at dose
      levels as low as 0.7 mSv.

PMID- 17549491
TI  - Early characterization of atherosclerotic coronary plaques with multidetector
      computed tomography in patients with acute coronary syndrome: a comparative study
      with intravascular ultrasound.
AB  - We compared 16-slice computed tomography (CT) with intravascular ultrasound
      (IVUS) in their ability to identify the culprit lesion, and to assess plaque
      characterization and vascular remodelling in acute coronary syndrome (ACS).
      Twenty patients were prospectively studied. Coronary plaque identification and
      characterization were compared using 16-slice CT and 40-MHz catheter-based IVUS.
      Minimum lumen area (MLA), cross-sectional vessel area (CVA) and vessel
      remodelling were determined for each comparable lesion. One hundred and sixty
      nine segments were compared and 84 plaques analysed. Sixteen-slice CT detected
      95% of culprit lesions (19/20). No feature suggestive of plaque rupture was
      detected by 16-slice CT. Attenuation measurements within all lesions revealed
      different values for hypoechoic (38 +/- 33 HU), hyperechoic (94 +/- 44 HU), and
      calcified plaques (561 +/- 216 HU), (P < 0.001). Agreement between 16-slice CT
      and IVUS on measuring MLA and CVA was evaluated using Bland-Altman analysis.
      Pearson and intra-class coefficient (ICC) were 0.81 and 0.70 for MLA, and 0.81
      and 0.36 for CVA, for 16-slice CT and IVUS, respectively. Agreement between both
      techniques for vessel positive remodelling was moderate (kappa = 0.54, P <
      0.001). Sixteen-slice CT has shown moderate accuracy in quantifying and
      characterizing coronary plaques compared with IVUS. Spatial resolution of 16
      slice CT remains a major limitation, however, to accurately assess the complex
      lesions involved in ACS.

PMID- 17549492
TI  - Perspectives for preventive screening with total body MRI.
AB  - Radiology has started to increasingly recognise its potential for screening with
      the advent of "whole-body" imaging techniques. This article briefly reviews
      prerequisites for successful screening, presents a quick summary of single-organ
      screening with magnetic resonance (MR) imaging, and introduces how this knowledge
      can be integrated into whole-body MR (wb-MR) screening. MR colonography has
      demonstrated its potential for screening. Wb-MR in the form of wb-MR angiography
      has already entered both clinical and screening settings; also, the search for
      metastases with wb-MR has been evaluated and has performed well when compared
      with other imaging modalities. But screening a group of healthy subjects requires
      more than feasibility and high accuracy of the screening test; thus, technical
      and ethical considerations are also presented. Wb-MR is only at its beginning and
      will in the near future certainly inspire many new research activities as well as
      transform the radiological market.

PMID- 17549493
TI  - FlexGuard: a new laser insertion sheath: functional aspects in ureterorenoscopy
      (URS).
AB  - The evolution of flexible ureteroscopes led to a widespread use for the
      management of upper urinary tract abnormalities. The cost of purchase,
      maintenance and the durability of these instruments has become a major issue.
      This work describes a new device to avoid damages due to incorrect use of the
      Holmium laser during insertion of the laser fibre. A laser fibre with an optical
      core of 271 and 430 muicrom outside diameter was slid inside the FlexGuard laser
      fibre insertion sheath (LISA laser products, Germany). The outside diameter of
      the sheath measures 2.7 F (0.9 mm) and 2.1 F (0.7 mm) luminal diameter. The
      distal fibre tip was brought up to a position app. 2 mm inside the distal end of
      the sheath. The loaded sheath was pushed through the working channel of various
      ureteroscopes which were in maximum deflection. With the insertion sheath
      protruding about 2 mm from the distal tip of the URS the fibre was effortless
      forwarded out of the sheath to approach the stone. Once the laser fibre was in
      position, the sheath was removed, to increase the volume of irrigation fluid
      during laser lithotripsy. The radius of curvature (ROC) of the URS in maximum
      deflection and the integrity of the working channel was investigated. Using the
      insertion sheath the laser fibre reached the working position without any
      recognition of scratching or resistance. The integrity of the ureterorenoscopes
      was checked thoroughly be manually operated manometry. No damage of the inner
      surface of the working channel occurred. The ROC of the instrument did not change
      significantly during this procedure. After removal of the sheath the ROC remained
      stable. With the extended use of ureteroscopy, durability and repair costs are of
      concern. Damage resulting from incorrect use of laser fibres is a major issue in
      this respect. FlexGuard proved to avoid this damage in all flexible ureteroscopes
      investigated without limiting their mobility.

PMID- 17549494
TI  - [Scleromalacia associated with varicella-zoster virus].
AB  - BACKGROUND: Scleromalacia usually appears following vasculitis in systemic
      rheumatoid diseases, especially as a late symptom of rheumatoid arthritis. CASE
      REPORT: A 67-year-old woman was referred to our hospital for further evaluation
      with the diagnosis of a "fast-growing tumor" of the left eye. Sixteen months ago
      she had suffered from herpes zoster ophthalmicus-associated keratouveitis and
      trabeculitis in the same eye. Scleromalacia associated with varicella-zoster
      virus (VZV) was diagnosed after the biomicroscopic and gonioscopic examination of
      the eye was completed and a systemic disease had been ruled out. One week after
      beginning systemic application of acyclovir (5 x 800 mg daily) and prednisolone
      (30 mg daily), the anterior chamber inflammation regressed and a fibrosis seemed
      to appear in the atrophic scleral area. CONCLUSION: Although scleral atrophy
      mostly appears as a late sign of systemic rheumatoid diseases, it might also
      develop secondary to infectious diseases. Scleromalacia associated with varicella
      zoster virus has been previously described only in a few cases. Scleromalacia is
      a vision-threatening complication of zoster ophthalmicus which responds well to
      combination therapy with systemic antiviral and anti-inflammatory agents.

PMID- 17549495
TI  - Effects of carotenoid supplementation on colour expression, oxidative stress and
      body mass in rehabilitated captive adult kestrels (Falco tinnunculus).
AB  - Carotenoids are considered a limited resource for animals because they are not
      synthesised by the body. Birds use carotenoids, mainly xanthophylls, for
      physiological functions, such as anti-oxidant activity, and for colour
      expression; hence, they need to shunt carotenoids between competitive demands.
      Recent studies suggest that the anti-oxidant role of xanthophylls might not be as
      important as previously thought and that at high concentrations they may, in
      fact, acquire pro-oxidant properties. In this work, we studied the effects of a
      moderate xanthophyll supplementation (115 mg of carotenoids/kg diet/day; 4 weeks)
      on serum carotenoids, serum concentration of reactive oxygen metabolites (ROMs),
      serum anti-oxidant capacity (OXY), the degree of oxidative stress (OS; ROMs/OXY x
      1,000), body mass, and skin colour, in rehabilitated captive adult Eurasian
      kestrels (Falco tinnunculus). The supplementation caused increased levels of
      serum carotenoids (approximately 90%), ROMs (approximately 82%), OS
      (approximately 115%) and an immediate loss of body mass (approximately 6.2%), but
      it did not affect OXY and tarsi skin hue. The red (approximately 16%) and yellow
      (approximately 15%) colorimetric components were increased after the first week
      of supplementation and the effect persisted during the rest of the experiment.
      Two months after the end of supplementation, serum carotenoids, OS and ROMs
      returned to baseline levels, however the body mass did not. Our findings suggest
      that, above a certain physiological threshold, carotenoids can cause detrimental
      effects. This is relevant for the trade-off between expression of sexual signals
      and the costs of maintaining/producing them.

PMID- 17549496
TI  - Thermal biology, torpor and behaviour in sugar gliders: a laboratory-field
      comparison.
AB  - Most studies on animal physiology and behaviour are conducted in captivity
      without verification that data are representative of free-ranging animals. We
      provide the first quantitative comparison of daily torpor, thermal biology and
      activity patterns, conducted on two groups of sugar gliders (Petaurus breviceps,
      Marsupialia) exposed to similar thermal conditions, one in captivity and the
      other in the field. Our study shows that activity in captive gliders in an
      outdoor aviary is restricted to the night and largely unaffected by weather,
      whereas free-ranging gliders omit foraging on cold/wet nights and may also forage
      in the afternoon. Torpor occurrence in gliders was significantly lower in
      captivity (8.4% after food deprivation; 1.1% for all observations) than in the
      field (25.9%), mean torpor bout duration was shorter in captivity (6.9 h) than in
      the field (13.1 h), and mean body temperatures during torpor were higher in
      captivity (25.3 degrees C) than in the field (19.6 degrees C). Moreover,
      normothermic body temperature as a function of air temperature differed between
      captive and free-ranging gliders, with a >3 degrees C difference at low air
      temperatures. Our comparison shows that activity patterns, thermal physiology,
      use of torpor and patterns of torpor may differ substantially between the
      laboratory and field, and provides further evidence that functional and
      behavioural data on captive individuals may not necessarily be representative of
      those living in the wild.

PMID- 17549497
TI  - Frog atrial natriuretic peptide and cGMP activate amiloride-sensitive Na(+)
      channels in urinary bladder cells of Japanese tree frog, Hyla japonica.
AB  - In our previous study, it was suggested that ANP and cGMP may increase Na(+)
      absorption in the urinary bladder of the Japanese tree frog, Hyla japonica. Thus,
      Na(+) transport activated by ANP was investigated electrophysiologically by using
      a cell-attached patch-clamp technique in freshly isolated cells from the urinary
      bladder. A predominant channel expressed was a low conductance Na(+) channel in
      the epithelial cells. The channel exhibited conductance for inward currents of
      4.9 +/- 0.2 pS, long open and closed times (c.a. 190 ms), and positive reversal
      potential. The channel activity was decreased under the pipette solution
      including 10(-6) M amiloride. These characteristics were similar to those of
      amiloride-sensitive Na(+) channels (ENaC). Addition of 10(-9) M ANP activated and
      significantly increased the ENaC activity from 0.58 +/- 0.09 to 1.47 +/- 0.34. On
      the other hand, mean amplitudes and conductance of single channel did not change
      significantly after the addition of ANP. Addition of 10(-5) M 8-Br-cGMP also
      activated the ENaC and significantly increased the channel activity from 0.56 +/-
      0.10 to 2.00 +/- 0.33. The addition of ANP failed to activate the ENaC in the
      presence of 10(-6) M amiloride. These results suggested that ANP and cGMP
      activate Na(+) transport via ENaC in the epithelial cells of frog urinary
      bladder.

PMID- 17549498
TI  - Reticulated platelet levels in patients with ulcerative colitis.
AB  - BACKGROUND AND AIMS: In this study, we investigated whether reticulated platelets
      (RP) would be useful markers in the evaluation of ulcerative colitis (UC)
      activity and also aimed to gain indirect information about the platelet kinetics.
      MATERIALS AND METHODS: Complete blood count, C-reactive protein, erythrocyte
      sedimentation rate, and proportion of RP were measured in 16 active, 21 inactive
      UC patients, and 20 healthy blood donors. UC activity was assessed by Truelove
      Witts criteria. RESULTS: Mean platelet count was increased in patients with
      active compared to inactive UC (p=0.008) or healthy donors (p=0.000). Mean
      platelet volume (MPV) was significantly decreased in patients with active
      compared to inactive (p=0.015) and healthy donors (p=0.001). RP values was
      significantly decreased in active and inactive UC groups compared to healthy
      donors (p=0.000, p=0.000, respectively), while there was no significant
      difference between active and inactive UC patients (p=0.980). Significant
      negative correlation between platelet count and MPV in patients with active UC
      (r=-0.542, p=0.030) was observed. CONCLUSIONS: RP values is reduced in active and
      inactive UC patients compared to healthy donors. To our knowledge, this is the
      first study about proportion of RP with UC in literature. However, the role of
      low RP values have not been determined clinically. Further studies are needed to
      evaluate the role of platelet abnormalities and changes in megakaryopoiesis
      caused by inflammatory state on low MPV and RP values during the course of UC.

PMID- 17549500
TI  - [Intracellular signaling pathways of synovial fibroblasts in rheumatoid
      arthritis].
AB  - Rheumatoid arthritis (RA) is a chronic autoimmune disease of still unknown
      etiology that results in characteristic destructive changes of the joints.
      Research of the past years has demonstrated that synovial fibroblasts play a
      central role in the initiation and perpetuation of these destructive changes.
      Stimulation of the synovial fibroblasts through complex and interacting
      intracellular signaling pathways results in a stable activation that is maintain
      even without continuous stimulation by inflammatory cells and their mediators.
      The pathological attachment to articular cartilage, increased secretion of matrix
      degrading enzymes and alterations in programmed cell death are main
      characteristics of synovial fibroblasts from patients with RA and result in the
      progressive destruction of articular structures. The permanent activation of a
      number of intracellular signaling pathways constitutes the underlying responsible
      mechanism for the activation of synovial fibroblasts in RA. These signaling
      pathways do not only show a high degree of complexity, but are also
      interconnected in multiple ways. This article summarizes recent findings on the
      activation of intracellular signaling pathways in fibroblasts and points to
      potential targets for novel therapeutic strategies.

PMID- 17549501
TI  - Immunohistochemical localization of NUB1, a synphilin-1-binding protein, in
      neurodegenerative disorders.
AB  - Recently, we showed that NUB1 is a synphilin-1-interacting protein and that NUB1,
      as well as synphilin-1, accumulates in Lewy bodies in Parkinson's disease (PD)
      and dementia with Lewy bodies (DLB), and glial cytoplasmic inclusions in multiple
      system atrophy (MSA). In this study, an investigation was further conducted to
      elucidate the immunohistochemical localization of NUB1 in various
      neurodegenerative disorders. In controls, anti-NUB1 antibody weakly immunolabeled
      neuronal perikarya. In PD and DLB, cortical and brainstem-type Lewy bodies, pale
      bodies and Lewy neurites were strongly immunolabeled with anti-NUB1. In MSA, NUB1
      immunoreactivity was found in the intracytoplasmic inclusions of both neuronal
      and oligodendroglial cells, neuronal nuclear inclusions, and swollen neurites. No
      NUB1 immunoreactivity was found in a variety of other neuronal or glial
      inclusions in other disorders, including Alzheimer's disease, Pick's disease,
      progressive supranuclear palsy, corticobasal degeneration, motor neuron disease
      and triplet-repeat diseases. These findings indicate that the abnormal
      accumulation of NUB1 is specific for alpha-synucleinopathy lesions. However,
      yeast two-hybrid assay demonstrated that NUB1 did not directly interact with
      alpha-synuclein.

PMID- 17549502
TI  - Structure of human BRCA2-RAD51 by molecular docking study.
AB  - BACKGROUND: [corrected] BRCA was the first breast cancer susceptibility gene to
      be identified and cloned. The interactions between the BRCA2 and the RAD51
      recombinase are essential for DNA repair by homologous recombination, failure of
      which can predispose to cancer. The availability of genetic tests for BRCA gene
      mutations prompted cancer geneticists to give information about genetic risk and
      to assess many women with a personal or family history of breast cancer to inform
      them of preventive measures. However, the knowledge on the complex,
      recombination, between BRCA2- RAD51 is limited. METHODS: Here, the author
      performs an analysis to study the molecular structure of human BRCA2-RAD51
      complex. RESULTS: The output 3D molecular structure from the combination between
      BRCA2-RAD51 is derived. CONCLUSION: The property as well as geometry of the
      derived complex was also presented.

PMID- 17549503
TI  - Cystosarcoma phyllodes of the breast: a rare diagnosis: case studies and review
      of literature.
AB  - Cystosarcoma phyllodes (CP), otherwise known as phyllodes tumour (PT) of the
      breast, is a very rare but locally aggressive fibroepithelial tumour in its
      malignant form, and accounts for 0.3-1% of all breast neoplasias. Using 4 cases
      reports with different histological classifications as examples (benign
      borderline-malignant), we describe the (differential) diagnosis and treatment
      options of this tumour entity and give an additional review of the available
      literature.

PMID- 17549504
TI  - Resection of extensive sellar tumors with extended endoscopic transseptal
      transsphenoidal approach.
AB  - The endoscope has recently been used to extensive sellar lesions, but the
      extended areas of the lesions and operative techniques vary from each study. Here
      we present our experience with extended endoscopic transseptal transsphenoidal
      (EETT) approach to 16 patients with extensive sellar lesion and evaluate the
      feasibility of EETT in different extensive sellar tumor resection. Sixteen
      patients with extensive sellar lesion were operated by EETT approach in this
      study. The approach included unilateral posterior septum mucosa resection,
      posterior septectomy, extended ethmoidectomy and sphenoidoctomy, four tumoral
      circumferences (bilateral, superior, inferior aspects) isolated and subsequently
      tumoral removal from outside to inside of the tumors obtained. This surgical
      procedure is satisfactory for sellar lesion with different juxtasellar extension.
      After surgery, CT scan and MR image showed that total removal of the tumor was
      achieved in 10 patients. Six patients who received subtotal resection were
      treated with postoperative radiation therapy or gamma knife surgery. Two patients
      developed postoperative cerebrospinal fluid leak that was successfully managed by
      conservative treatment within 6 days after surgery. No other new postoperative
      endocrinological or neurological defects occurred. Six months to 5 years follow
      up indicated that all 16 patients with the visual disturbances and 4 patients
      with endocrine impairments have recovered or improved. One patient with malignant
      meningioma died due to recurrence of the tumor 2 years postoperation. Another one
      patient with malignant inverted papilloma recurred 1 year postoperation and
      underwent operation and radiation therapy again. The EETT approach might better
      facilitate the removal of different extensive sellar lesions with maximal
      preservation of important anatomical structures and nasal function.

PMID- 17549505
TI  - Tumoral mass presenting in the nasomalar region arising from the lateral nasal
      wall: pleomorphic adenoma.
AB  - Pleomorphic adenoma is the most common benign salivary gland tumor. Although the
      major salivary glands are the most common sites of its origin, it can also occur
      in the minor salivary glands of the oral cavity and rarely in the neck, ear,
      nasal cavity and larynx. We report a rare case of intranasal pleomorphic adenoma
      arising from lateral nasal wall and discuss the clinical presentation, diagnosis
      and treatment approaches with the review of the literature.

PMID- 17549506
TI  - Long-term corrosion and leaching of depleted uranium (DU) in soil.
AB  - Corrosion and leaching of depleted uranium (DU) was investigated for 3 years
      using six DU munitions (145-264 g DU) each buried in a column with a soil core of
      about 3.3 kg dry soil mass. The columns were installed in an air-conditioned
      laboratory. Each week they were irrigated and (238)U was determined in the
      effluents by inductively coupled plasma mass spectrometry. In addition, (235)U
      was measured occasionally to assure that the (238)U was predominantly from the DU
      munition. On average, 14.5 g corresponding to 7.9% of the initial DU mass was
      corroded after 3 years, indicating an increased corrosion as compared to the
      first year of observation. The leaching rates increased much stronger than the
      corrosion rates by factors of more than 100, resulting in a mean total amount of
      leached (238)U of 13 mg as compared to 0.03 mg after the first year. Uranium
      species identified in the seepage water by time-resolved laser-induced
      fluorescence spectroscopy were mainly hydroxo and carbonate compounds, while
      those in the corroded material were phosphate compounds. It is concluded that the
      dramatic increase of the leaching and its large temporal variability do not allow
      any extrapolation for the future. However, the high (238)U concentrations
      observed in the seepage water highlight the need for further investigations on
      the transport of (238)U through soil, in particular with regard to the potential
      future (238)U contamination of groundwater in areas affected by DU weapons.

PMID- 17549507
TI  - Characterization of a new SUMO-1 nuclear body (SNB) enriched in pCREB, CBP, c-Jun
      in neuron-like UR61 cells.
AB  - The neuron-like UR61 cell is a stable PC12 subline that contains a mouse N-ras
      oncogene. Dexamethasone (Dex) treatment induces a neuron-like differentiation,
      which is associated with neuritogenesis and nuclear expression of the
      glucocorticoid receptor and c-Jun. In differentiated UR61 cells, small ubiquitin
      like modifiers 1 (SUMO-1) is concentrated in a new category of SUMO-1 nuclear
      bodies (SNBs) distinct from promyelocytic leukemia (PML) bodies by their large
      size and absence of PML protein. SNBs are 1 to 3 mum in diameter and exhibit a
      fine granular texture by electron microscopy. They are free of splicing factors
      and transcription foci and show spatial associations with Cajal bodies. In
      addition to SUMO-1 and the E2-conjugating enzyme Ubc9, which is essential for
      sumoylation, SNBs concentrate the transcriptional regulators CBP, CREB, and c
      Jun. Moreover, transfection experiments demonstrate that SNBs accumulate the
      active conjugating form of SUMO-1 but not the conjugation defective variant of
      SUMO-1, supporting that SNBs are sites of sumoylation. Our results suggest that
      SNBs play a role in the control of the nucleoplasmic concentration of
      transcription regulators involved in neuroprotection and survival of the UR61
      cells.

PMID- 17549508
TI  - Age estimation in children by measurement of open apices in teeth: a European
      formula.
AB  - The aim of the present paper was to improve and expand research with a larger
      number of children from various European countries and to provide a common
      formula useful for all these countries. Orthopantomographs taken from 2,652
      European Caucasian children (1,382 boys, 1,270 girls) aged between 4 and 16 years
      were analyzed. The children came from Croatia, Germany, Kosovo, Italy, Slovenia,
      Spain, and the UK. Following the pilot study, subjects' age was modeled as a
      function of gender (g), morphological variables (predictors) x 5(second
      premolar), s (sum of normalized open apices) N 0, and the first-order interaction
      between s and N 0. The results showed that all these variables contributed
      significantly to the fit, so that all were included in the regression model,
      yielding the following linear regression formula: Age = 8.387 + 0.282 g - 1.692 x
      5 + 0.835 N 0 - 0.116 s - 0.139 s x N 0, where g is a variable, 1 for males and 0
      for females. The equation explained 86.1% (R2 = 0.861) of total deviance. The
      median of the residuals (=observed age minus predicted age) was -0.114 years,
      with (RefB.2) interquartile range = 1.22 years.

PMID- 17549509
TI  - Amblyopia and Strabismus Questionnaire (A&SQ): clinical validation in a historic
      cohort.
AB  - BACKGROUND: We recently developed the Amblyopia & Strabismus Questionnaire (A&SQ)
      to assess the quality of life in amblyopia and/or strabismus patients, and
      evaluated its content and criterion validity. The A&SQ was now validated
      clinically by correlating its outcome with past and current orthoptic parameters
      in a historic cohort of amblyopia and/or strabismus patients. METHODS: The cohort
      was derived from all 471 patients who were treated by occlusion therapy in the
      Waterland Hospital in Purmerend between 1968 and 1974 and born between 1962 and
      1972. All children with insufficient visual acuity from the Waterland area had
      been referred to a single ophthalmologist and orthoptist. Of these, 203 were
      traced, and 174 filled out the A&SQ. In 137 of these, binocular vision, visual
      acuity, and angle of strabismus were reassessed 30-35 years after occlusion
      therapy. These clinical parameters were correlated with the five A&SQ domains:
      "distance estimation", "visual disorientation", "fear of losing the better eye",
      "diplopia", and "social contact and cosmetic problems". RESULTS: The current
      acuity at distance of the amblyopic eye and reading acuity of the amblyopic eye
      correlated significantly with all five A&SQ domains (significance level P = 0.01
      P = 0.05). Weaker correlations were found for binocularity. In spite of the
      expectation that stereopsis should strongly correlate with the domain "distance
      estimation", and angle of strabismus with the domain "social contact and cosmetic
      problems", the acuity of the amblyopic eye was the overall dominant parameter.
      CONCLUSIONS: The adult acuity of the amblyopic eye seems the most important
      clinical determinant for quality of life in amblyopia and/or strabismus patients,
      even in domains of distance estimation, visual disorientation, and social contact
      and cosmetic problems, although intermediate determinants cannot be excluded.

PMID- 17549510
TI  - In vitro liberation of charged gold atoms: autometallographic tracing of gold
      ions released by macrophages grown on metallic gold surfaces.
AB  - The present study demonstrates that cultured macrophages are able to liberate
      gold ions from metallic gold surfaces, a process suggested to be called
      "dissolucytosis", in a way analogous to the release taking place when metallic
      implants are placed in a body. Using the ultra-sensitive autometallographic (AMG)
      technique, we demonstrate that murine macrophages grown on a surface of metallic
      gold liberate gold ions. Ultra-structural AMG reveals that the gold ions are
      located in an ultra-thin membrane-like structure, "the dissolution membrane",
      intervened between the macrophages and the metal surface. The presence of AMG
      silver enhanced gold nanoparticles in the dissolution membrane proves that the
      release of charged gold atoms takes place extracellularly. The dissolution
      membrane is most likely secreted and chemically controlled by the "dissolucytes",
      here macrophages, and the membrane is essential for the dissolution of metal
      implants and particles, which cannot be phagocytosed. Our findings support the
      notion that whenever a metallic gold surface is attacked by dissolucytes, gold
      ions are liberated and taken up by surrounding cells. As gold ions can suppress
      the inflammatory process, it is reasonable to expect that when dissolucytosis
      takes place in the living organism the liberated gold ions will cause local
      immunosuppression.

PMID- 17549511
TI  - A new method to distinguish the hyponatremia of electrolyte loss from that due to
      pure solvent changes.
AB  - Estimates of solute and solvent changes during electrolyte abnormalities are
      valid only when either total body water (TBW) or solute content do not change,
      while it cannot be established which one of these is altered. The present paper
      provides a method capable of distinguishing these two different conditions. When
      only solvent changes, the respective concentration ratios of plasma (P) solutes
      PCl/PNa, POAN: /PNa, PCl/POAN: (POAN: = anions other than Cl) remain unchanged.
      Moreover, PNa(1)/PNa(0) (the ratio of PNa during the derangement over the normal
      value, indicated by subfix (1) and (0), respectively) = PCl(1)/PCl(0) = POAN:
      (1)/POAN: (0.) When these constraints are met, the abnormality is due only to a
      TBW change, which is easily calculated and corrected. When they are not met, the
      exact change in Na content is correctly calculated assuming no variation in TBW.
      These calculations could still be useful even in the presence of TBW
      modifications, where they represent minimum estimates of electrolyte losses. The
      formulas were validated by computer simulations generating true electrolyte
      concentrations, which were then used to back calculate the changes in their
      contents and extra/intra-cellular volumes. Since the predicted results were
      significantly correlated with the true data, the method was transferred to 24
      patients with electrolyte disturbances, who met the above constraints. The
      calculated volume changes were significantly correlated with those obtained by
      body weight measurements (regression coefficient = 0.94, P < 0.0001), while the
      quantitative estimates of Na deficit predicted the PNa values measured after
      corrective treatment (P < 0.0001). This new method may prove valuable in
      diagnosing and treating electrolyte derangements.

PMID- 17549512
TI  - Role of focal adhesion kinase (FAK) in renal ischaemia and reperfusion.
AB  - Focal adhesion kinase (FAK), a non-receptor tyrosine kinase, plays important
      roles in cell migration, cell proliferation and cell survival. Because these
      processes participate in the restoration of tubular integrity in renal ischaemia
      and reperfusion, FAK expression and phosphorylation at Tyr-397, the latter
      indicative of its activity, were examined in the different kidney zones by
      Western blot analysis and immunohistochemistry. Expression and phosphorylation of
      FAK were also studied in Madin-Darby canine kidney (MDCK) and medullary thick
      ascending limb (mTAL) cells after ATP depletion and repletion. In control rat
      kidneys, FAK expression in outer and inner medulla exceeded that in cortex, and
      phosphorylation of FAK at Tyr-397 was most pronounced in the inner medulla.
      Although this expression pattern was not affected by 20 (40, 60)-min ischaemia
      and 20 (40, 60)-min ischaemia followed by 60-min or 24-h reperfusion, FAK
      phosphorylation was significantly reduced in all kidney zones immediately after
      ischaemia, but increased during reperfusion, exceeding control values in the
      outer and inner medulla. ATP depletion and repletion of MDCK and mTAL cells were
      associated with a decrease in FAK phosphorylation during ATP depletion, followed
      by an increase during repletion. Rephosphorylation of FAK after ATP repletion was
      enhanced by N-acetylcysteine, a reactive oxygen species scavenger. ATP depletion
      disrupted focal adhesions in MDCK cells. Their reformation after ATP repletion
      paralleled the increase in FAK phosphorylation. These findings suggest an
      essential role for FAK-signalling during renal ischaemia and early reperfusion.

PMID- 17549513
TI  - Pathophysiology of HCN channels.
AB  - Hyperpolarization-activated cation currents termed I (f/h) are observed in many
      neurons and cardiac cells. Four genes (HCN1-4) encode the channels underlying
      these currents. New insights into the pathophysiological significance of HCN
      channels have been gained recently from analyses of mice engineered to be
      deficient in HCN genes. Lack of individual subunits results in markedly different
      phenotypes. Disruption of HCN1 impairs motor learning but enhances spatial
      learning and memory. Deletion of HCN2 results in absence epilepsy, ataxia, and
      sinus node dysfunction. Mice lacking HCN4 die during embryonic development and
      develop no sinoatrial node-like action potentials. In the present review, we
      summarize the physiology and pathophysiology of HCN channel family members based
      primarily on information from the transgenic mouse models and on data from human
      patients carrying defects in HCN4 channels.

PMID- 17549514
TI  - Fine mapping of S31, a gene responsible for hybrid embryo-sac abortion in rice
      (Oryza sativa L.).
AB  - Partial abortion of female gametes and the resulting semi-sterility of indica x
      japonica inter-subspecific rice hybrids have been ascribed to an allelic
      interaction, which can be avoided by the use of wide compatibility varieties. To
      further understand the genetic mechanism of hybrid sterility, we have constructed
      two sets of hybrids, using as male parent either the typical japonica variety
      Asominori, or the wide compatibility variety 02428; and as female, a set of 66
      chromosome segment substitution lines in which various chromosomal segments from
      the indica variety IR24 have been introduced into a common genetic background of
      Asominori. Spikelet semi-sterility was observed in hybrid between CSSL34 and
      Asominori, which is known to carry the sterility gene S31 (Zhao et al. in
      Euphytica 151:331-337, 2006). Cytological analysis revealed that the semi
      sterility of the CSSL34 x Asominori hybrid was caused primarily by partial
      abortion of the embryo sac at the stage of the mitosis of the functional
      megaspore. A population of 1,630 progeny of the three-way cross (CSSL34 x 02428)
      x Asominori was developed to map S31. Based on the physical location of linked
      molecular markers, S31 was thereby delimited to a 54-kb region on rice chromsome
      5. This fragment contains eight predicted open reading frames, four of which
      encode known proteins and four putative proteins. These results are relevant to
      the map-based cloning of S31, and the development of marker-assisted transfer of
      non-sterility allele inducing alleles to breeding germplasm, to allow for a more
      efficient exploitation of heterosis in hybrid rice.

PMID- 17549515
TI  - Overexpression of OsCOIN, a putative cold inducible zinc finger protein,
      increased tolerance to chilling, salt and drought, and enhanced proline level in
      rice.
AB  - Rice (Oryza sativa L.) plant is sensitive to chilling, particularly at early
      stages of seedling development. Here a novel cold-inducible gene, designated
      OsCOIN (Oryza sativa cold-inducible), was isolated and characterized. Results
      showed that OsCOIN protein, a RING finger protein, was localized in both nuclear
      and cytoplasm membrane. OsCOIN is expressed in all rice organs and strongly
      induced by low temperature, ABA, salt and drought. Over-expression of OsCOIN in
      transgenic rice lines significantly enhanced their tolerance to cold, salt and
      drought, accompanied by an up-regulation of OsP5CS expression and an increase of
      cellular proline level.

PMID- 17549516
TI  - A pilot screening of prevalence of atopic states and opisthorchosis and their
      relationship in people of Tomsk Oblast.
AB  - The study was aimed to estimate the relationship between the prevalence of
      allergic disease and helminth invasion by the trematode Opisthorchis felineus in
      rural and urban populations of Tomsk Oblast (West Siberia, Russia). Two hundred
      and one people from Kargasok village of Tomsk Oblast and 196 from the city of
      Tomsk were screened for the presence of atopy and O. felineus invasion.
      Opisthorchosis was found in 66 participants (32.8%) from Kargasok and in 22
      people (11.2%) from Tomsk. Atopic diseases were more common in the urban
      population than in the rural: 52.8 and 31.4%, respectively. Positive skin-prick
      tests were significantly higher in the urban population than in rural people:
      83.2 vs 24.4%, respectively. It was found that in the city, the presence of
      antibodies to O. felineus negatively correlates with the atopic sensitization by
      skin-prick tests. However, in the village, opisthorchosis was positively
      associated with atopic diseases. The data obtained confirm the negative
      association of rural lifestyle and atopic diseases prevalence and indicate that
      O. felineus invasion might be a modifying factor of this relationship in Tomsk
      Oblast.

PMID- 17549518
TI  - Peptide immunocytochemistry of neurons projecting to the retrocerebral complex in
      the blow fly, Protophormia terraenovae.
AB  - Antisera against a variety of vertebrate and invertebrate neuropeptides were used
      to characterize neurons with somata in the pars intercerebralis (PI), pars
      lateralis (PL), and subesophageal ganglion (SEG), designated as PI neurons, PL
      neurons, and SEG neurons, respectively, all of which project to the retrocerebral
      complex in the blow fly, Protophormia terraenovae. Immunocytochemistry combined
      with backfills through the cardiac-recurrent nerve revealed that at least two
      pairs of PI and SEG neurons for each were FMRFamide-immunoreactive.
      Immunoreactivity against [Arg7]-corazonin, beta-pigment-dispersing hormone (beta
      PDH), cholecystokinin8, or FMRFamide was observed in PL neurons. Immunoreactive
      colocalization of [Arg7]-corazonin with beta-PDH, [Arg7]-corazonin with
      cholecystokinin8, or beta-PDH with FMRFamide was found in two to three somata in
      the PL of a hemisphere. Based on their anatomical and immunocytochemical
      characteristics, PI neurons were classified into two types, PL neurons into six
      types, and SEG neurons into two types. Fibers in the retrocerebral complex showed
      [Arg7]-corazonin, beta-PDH, cholecystokinin8, and FMRFamide immunoreactivity.
      Cholecystokinin8 immunoreactivity was also detected in intrinsic cells of the
      corpus cardiacum. The corpus allatum was densely innervated by FMRFamide
      immunoreactive varicose fibers. These results suggest that PI, PL, and SEG
      neurons release [Arg7]-corazonin, beta-PDH, cholecystokinin8, or FMRFamide-like
      peptides from the corpus cardiacum or corpus allatum into the hemolymph, and that
      some PL neurons may simultaneously release several neuropeptides.

PMID- 17549517
TI  - Congenital Plasmodium falciparum malaria in sub-Saharan Africa: a rarity or
      frequent occurrence?
AB  - It is still debatable whether congenital Plasmodium falciparum malaria is a
      rarity or a frequent occurrence in sub-Saharan Africa. The objective of this
      report is to review scientific information and findings from investigations
      conducted in sub-Saharan Africa on the occurrence of congenital malaria to
      highlight the need for development of appropriate public health policy on
      prevention, care, treatment, and support activities. Studies conducted in sub
      Saharan Africa within the last two decades (1986 to 2006) that investigated
      congenital or transplacental malaria were identified using the Medline-Entrez
      Pubmed search and systematically reviewed. References from selected publications
      obtained from a Google search were also used to identify additional relevant
      literature for the review. Five of the studies reviewed indicated that congenital
      malaria is a rare event in sub-Saharan Africa with prevalence ranging from 0% to
      0.7% although maternal malaria parasitemia rates of between 24.8 and 54.4% were
      obtained. Nine other studies noted that congenital malaria was not uncommon, with
      prevalence reaching up to 37%. These studies also noted high frequency of
      neonatal peripheral parasitemia ranging from 4.0 to 46.7%. Congenital malaria
      should be suspected and investigated in babies whose mothers are parasitemic,
      particularly if the babies are febrile.

PMID- 17549519
TI  - Majority of TcRbeta+ T-lymphocytes located in thymus and midgut of the bony fish,
      Dicentrarchus labrax (L.).
AB  - Real-time polymerase chain reaction (PCR) and in situ hybridization analyses were
      performed to investigate the occurrence and distribution of T-lymphocytes
      expressing TcRbeta in intestine and lymphoid tissues of the bony fish,
      Dicentrarchus labrax (sea bass). Immunohistochemistry with the monoclonal
      antibody DLT15 (pan-T-cell marker) was carried out to compare the cytology,
      distribution and number of T-cells and TcRbeta+ cells in the various sampled
      lymphoid organs. The highest TcRbeta expression was revealed by real-time PCR in
      the thymus, with high levels also being found in the gut. In the thymus, DLT15+
      and TcRbeta+ cell populations were concentrated in the cortex and TcRbeta+ cells
      were notably reactive at the cortical-medullary border, suggesting a specialized
      role of this region in thymocyte selection. The density of DLT15+ T-cells
      increased from the anterior to posterior intestine, whereas TcRbeta+ lymphocytes
      were more numerous in the middle intestine compared with other segments. The
      existence, in fish thymus, of a medulla and a cortex comparable with those of
      mammals is revealed by this study. The concentration of TcRbeta+ cells in the sea
      bass midgut also strongly suggests a special role of this intestinal segment in
      antigen-specific cellular immunity. The large population of TcRbeta(-)/DLT15+ T
      cells in the posterior gut can probably be ascribed to the TcRgammadelta
      phenotype fraction.

PMID- 17549520
TI  - Comparative analysis of maternal-fetal interface in preeclampsia and preterm
      labor.
AB  - The maternal-fetal interface, a chimeric structure, is formed when fetal
      cytotrophoblasts (CTBs) from the placenta invade the uterine wall and its
      resident vasculature. In preeclampsia (PE), interstitial and endovascular
      invasion are often shallow, and fewer spiral arterioles are breached in toto. Our
      previous work has shown that faulty CTB differentiation to an invasive phenotype
      is a contributing factor. Here, we have tested the hypothesis that the
      constellation of morphological and molecular defects that are associated with PE
      are unique to this condition. Specifically, we have compared the histology of the
      maternal-fetal interface and CTB expression of stage-specific antigens in PE and
      in preterm labor (PTL) with or without inflammation. In the absence of
      inflammation, biopsies obtained after PTL were near normal at histological and
      molecular levels. In accord with previously published data, PE had severe
      negative effects on the endpoints analyzed. Biopsies obtained after PTL with
      inflammation had an intermediate phenotype. Our results suggest that the maternal
      fetal interface from cases of PTL without inflammation can be used for
      comparative purposes, e.g., as age-matched controls, in studies of the effects of
      PE on cells in this region.

PMID- 17549521
TI  - How does pattern of feeding and rate of nutrient delivery influence conditioned
      food preferences?
AB  - Ruminant herbivores have been shown to learn about food properties by associating
      food flavours with the food's post-ingestive consequences. Previous
      experimentation supporting the conditioned food aversion/preference hypothesis
      has generally employed very simple diet learning tasks which do not effectively
      represent the wide range of foods selected within single bouts typical of wild,
      free-ranging ruminant herbivores. We tested the ability of a ruminant herbivore
      to associate a food with artificially administered nutrient rewards in a designed
      experiment where we altered the temporal pattern of encounter with the food as
      well as the nature (fast or slow reward) of the post-ingestive outcome. Twenty
      four goats were offered branches of Sitka spruce (SS) and Norway spruce (NS) for
      4 h per day on two days per week for five weeks. The pattern of feeding varied
      with treatment such that the species on offer changed every hour (short) or every
      2 h (long). The energy treatment altered the reward delivered during Sitka
      consumption so that animals were dosed either with predominantly sugar (rapidly
      fermented), predominantly starch (slower fermentation rate), or with water
      (placebo). Preference was measured on the day following each learning day. We
      expected that goats would find it easier to associate SS with post-ingestive
      rewards when the duration of encounter was longest, and that associations would
      be stronger with the most rapidly digested post-ingestive reward. In the event,
      goats did not alter their consumption of SS in response to the treatments. Our
      results suggest that at the scale of temporal resolution of encounters with
      different plant species (1-2 h), and at the different rates of experiencing post
      ingestive consequences tested in this experiment, ruminants do not appear to
      discriminate the nutritive properties of foods predominantly through a post
      ingestive feedback mechanism. They must, instead, use a range of cues-including
      post-ingestive consequences-to assess food properties.

PMID- 17549522
TI  - Can measures of prey availability improve our ability to predict the abundance of
      large marine predators?
AB  - Apex marine predators can structure marine communities, so factors underlying
      their abundance are of broad interest. However, such data are almost completely
      lacking for large sharks. We assessed the relationship between tiger shark
      abundance, water temperature, and the availability of a variety of known prey
      over 5 years in Western Australia. Abundance of sharks in four size categories
      and the density of prey (cormorants, dugongs, sea snakes, sea turtles) were
      indexed using daily catch rates and transects, respectively. Across all sizes,
      thermal conditions were a determinant of abundance, with numerical peaks
      coinciding with periods of high water temperature. However, for sharks exceeding
      300 cm total length, the inclusion of dugong density significantly improved
      temperature-based models, suggesting that use of particular areas by large tiger
      sharks is influenced by availability of this sirenian. We conclude that large
      marine predator population models may benefit from the inclusion of measures of
      prey availability, but only if such measures consider prey types separately and
      account for ontogenetic shifts in the diet of the predator in question.

PMID- 17549523
TI  - Territory occupancy rate of goshawk and gyrfalcon: no evidence of delayed
      numerical response to grouse numbers.
AB  - Two recent studies on territory occupancy rates of goshawk Accipiter gentilis and
      gyrfalcon Falco rusticolus report a 2-3-year-delayed numerical response to grouse
      numbers, which is a requirement for a hypothesis of predator-generated grouse
      cycles. The time lags were assumed to reflect the average age of sexual maturity
      in the raptor species. In southern Norway, however, subadult (two-year-old)
      goshawk hens occupied only 18-25% of territories where occupancy was not recorded
      in the preceding year, and there was no significant relationship between the
      proportion of subadults among recruits and grouse indices two years earlier. We
      argue that territory occupancy rates are not appropriate indices of total raptor
      population levels, but rather reflect the proportion of territorial pairs that
      attempt to nest. Because this depends on the body condition of the hens,
      fluctuations in other important winter resident prey species (most important for
      the goshawk) and winter weather (most important for the gyrfalcon) should also be
      addressed. During 1988-2006, the annual proportion of goshawk territories with
      recorded nesting attempts in southern Norway was most closely related to the
      preceding autumn's population indices of black grouse Tetrao tetrix and mountain
      hare Lepus timidus, whereas the annual proportion of gyrfalcon territories with
      observations of falcons or with confirmed breeding attempts in central Norway
      were best explained by population indices of willow grouse Lagopus lagopus and
      ptarmigan L. mutus from the previous autumn, and by December temperatures. Hence,
      our studies do not support the predation hypothesis for grouse cycles.

PMID- 17549524
TI  - Screening for hypercalciuria in schoolchildren: what should be the criteria for
      diagnosis?
AB  - The methodologies to diagnose hypercalciuria have not yet been standardized. The
      aims of this study were to assess the correlation between urinary
      calcium/creatinine ratio (UCa/Cr) > or = 0.21 (mg/mg) and 24 h urinary calcium
      excretions and to determine the reference values of the UCa/Cr ratio among a
      large population of schoolchildren in southern Turkey. Non-fasting, second
      morning urine samples were collected from 2,143 children aged 7-14 years. In
      children with suspected hypercalciuria [UCa/Cr > or = 0.21 (mg/mg)], 24 h urine
      samples were collected. The 95th percentile values of the UCa/Cr ratio for each
      age were calculated and showed a decrease in value with advancing age. In all,
      269 (12.5%) of the children had UCa/Cr > or = 0.21 (mg/mg), of whom 66 (24.5%)
      had daily urinary calcium excretion > or =4 mg/kg per day. A weak correlation was
      found between spot UCa/Cr ratios and daily urinary calcium excretions in children
      with UCa/Cr > or = 0.21 (r = 0.27). We conclude that a spot UCa/Cr ratio of 0.21
      (mg/mg) as the upper limit of normal cannot be used universally to define
      hypercalciuria. Age-specific reference values for UCa/Cr should be established
      for each population, to be used as a screening test for hypercalciuria, and the
      definite diagnosis should be established with 24 h urinary calcium excretion
      whenever possible.

PMID- 17549525
TI  - Development of a clinical diagnosis support tool to identify patients with lumbar
      spinal stenosis.
AB  - No clinical diagnostic support tool can help identify patients with LSS. Simple
      diagnostic tool may improve the accuracy of the diagnosis of LSS. The aim of this
      study was to develop a simple clinical diagnostic tool that may help physicians
      to diagnose LSS in patients with lower leg symptoms. Patients with pain or
      numbness of the lower legs were prospectively enrolled. The diagnosis of LSS by
      experienced orthopedic specialists was the outcome measure. Multivariable
      logistic regression analysis identified factors that predicted LSS; a simple
      clinical prediction rule was developed by assigning a risk score to each item
      based on the estimated beta-coefficients. From December 2002 to December 2004,
      104 orthopedic physicians from 22 clinics and 50 hospitals evaluated 468
      patients. Two items of physical examination, three items of patients' symptom,
      and five items of physical examination were included in the final scoring system
      as a result of multiple logistic regression analysis. The sum of the risk scores
      for each patient ranged from -2 to 16. The Hosmer-Lemeshow statistic was 11.30 (P
      = 0.1851); the area under the ROC curve was 0.918. The clinical diagnostic
      support tool had a sensitivity of 92.8% and a specificity of 72.0%. The
      prevalence of LSS was 6.3% in the bottom quartile of the risk score (-2 to 5) and
      99.0% in the top quartile (12 to 16). We developed a simple clinical diagnostic
      support tool to identify patients with LSS. Further studies are needed to
      validate this tool in primary care settings.

PMID- 17549526
TI  - Inter- and intraobserver reliability assessment of the Cobb angle: manual versus
      digital measurement tools.
AB  - The objective of this study is to determine the intraobserver and interobserver
      reliability of end vertebra definition and Cobb angle measurement using printed
      and digital radiographs of 48 patients with scoliosis. The Cobb angle and the end
      vertebra were assessed by six observers in 48 patients with scoliosis using
      printed and digital radiographs. Definition of end vertebra and measurement of
      the Cobb angle was repeated three times with a 3 week interval. Intraclass
      correlation coefficients (ICC) were used to determine the interobserver and
      intraobserver reliabilities. 95% prediction limits for the errors in measurements
      are provided. For the Cobb angle a mean ICC of 0.97 was determined for intra- and
      interobserver reliability measurement of the printed radiographs. For the
      electronic radiographs a mean ICC value of 0.93 was determined for interobserver
      reliability and a mean ICC value of 0.96 for intraobserver reliability.
      Intraobserver ICC for definition of end vertebrae was 0.8 for both methods.
      Interobserver ICC was 0.83 for the manual and 0.74 in the digital method. One
      pitfall in angle measurement implies the Cobb method itself which measures in two
      dimensions. Until we develop a proper tri-dimensional measuring system an error
      is introduced. For the Cobb angle measurement the definition of end vertebrae
      introduces the main source of error. Digital radiography does not improve the
      measurement accuracy.

PMID- 17549527
TI  - Kinematics of the lumbar spine in trunk rotation: in vivo three-dimensional
      analysis using magnetic resonance imaging.
AB  - In vivo three-dimensional (3D) kinematics of the lumbar spine has not been well
      evaluated by the conventional methods because of their methodological
      limitations, while 3D intervertebral motions have been quantitatively determined
      by cadaver studies. We thus developed a novel 3D analyzing system for the
      relative motions of individual vertebrae using 3D magnetic resonance imaging
      (MRI) and analyzed in vivo 3D intervertebral motions of the lumbar spine during
      trunk rotation. Ten healthy volunteers underwent 3D MRI of the lumbar spine in
      nine positions with 15 degrees increments during trunk rotation (0 degrees , 15
      degrees , 30 degrees , 45 degrees , and maximum). Relative motions of the lumbar
      spine were calculated by automatically superimposing a segmented 3D MRI of the
      vertebra in the neutral position over images of each position using the voxel
      based registration method. These 3D motions were represented with 6 degrees of
      freedom by Euler angles and translations on the coordinate system. The mean axial
      rotation of ten healthy volunteers of each lumbar spinal segment in 45 degrees
      trunk rotation to each side ranged from 1.2 degrees to 1.7 degrees . Coupled
      flexion with axial rotation was observed at the segments from L1/2 to L5/S1.
      Coupled lateral bending of the segments from L1/2 to L4/5 was in the opposite
      direction of the trunk rotation, while that of T12/L1 and L5/S1 was in the same
      direction. The direction of the coupled lateral bending in the present study was
      different from that in the previous cadaver study only at L4/5. This difference
      might result from the non-load state of the supine position in the current study
      and/or the non-physiological state in the cadaver study. Our system has two
      limitations: (1) the study was conducted with each volunteer in the supine
      position, and (2) because the rotation device regulated trunk rotation, trunk
      rotation might not have been physiological. In vivo 3D intervertebral motions of
      the lumbar spine during trunk rotation were evaluated using our novel motion
      analysis system. These data may be useful for the optimal orthopaedic management
      of lumbar spinal disorders.

PMID- 17549528
TI  - Structures and aromaticity of Cationic closo-BnHn-3(CO)3+ (n = 5-12).
AB  - Structures and stabilities of tricarbonyl closo-boranes cation, BnHn-3(CO)3+ (n =
      5-12), isolobal with cationic closo-carboranes C3Bn-3Hn+, have been investigated
      at the B3LYP/6-311+G** level of theory. The most stable positional isomers of
      individual cluster are in agreement with those of closo-C3Bn-3Hn+ clusters except
      for n = 8 and 10. Energetic analysis identifies closo-B6H3(CO)3+, closo
      B10H7(CO)3+ and closo-B12H9(CO)3+ as the most stable cages. It is also found that
      closo-BnHn-3(CO)3+ is much less strained than closo-C3Bn-3Hn+. The negative
      nucleus independent chemical shifts (NICS) at the cage center reveal three
      dimensional aromaticity of the closo-BnHn-3(CO)3+ cages. The CO stretching
      frequencies have been computed in advance to aid experimental study.

PMID- 17549529
TI  - Age at onset in sod1-mediated amyotrophic lateral sclerosis shows familiality.

PMID- 17549530
TI  - Capuchin monkeys (Cebus apella) succeed in a test of quantity conservation.
AB  - Nonhuman animals demonstrate a number of impressive quantitative skills such as
      counting sets of items, comparing sets on the basis of the number of items or
      amount of material, and even responding to simple arithmetic manipulations. In
      this experiment, capuchin monkeys were presented with a computerized task
      designed to assess conservation of discrete quantity. Monkeys first were trained
      to select from two horizontal arrays of stimuli the one with the larger number of
      items. On some trials, after a correct selection there was no feedback but
      instead an additional manipulation of one of those arrays. In some cases, this
      manipulation involved moving items closer together or farther apart to change the
      physical arrangement of the array but not the quantity of items in the array. In
      other cases, additional items were added to the initially smaller array so that
      it became quantitatively larger. Monkeys then made a second selection from the
      two arrays of items. Previous research had shown that rhesus monkeys (Macaca
      mulatta) succeeded with this task. However, there was no condition in that study
      in which items were added to the smaller array without increasing its quantity to
      a point where it became the new larger array. This new condition was added in the
      present experiment. Capuchin monkeys were sensitive to all of these
      manipulations, changing their selections when the manipulations changed which
      array contained the larger number of items but not when the manipulations changed
      the physical arrangement of items or increased the quantity in one array without
      also reversing which of the two arrays had more items. Therefore, capuchin
      monkeys responded on the basis of the quantity of items, and they were not
      distracted by non-quantitative manipulations of the arrays. The data indicate
      that capuchins are sensitive to simply arithmetic manipulations that involve
      addition of items to arrays and also that they can conserve quantity.

PMID- 17549531
TI  - Spillover of cause-specific longevity interventions: an independent mortality
      risk model.
AB  - As an alternative to the "competing mortality risk model", this paper presents an
      "independent mortality risk model" in which the complementarity among various
      longevity investments is less obvious. In studying spillover effects of cause
      specific longevity interventions, it distinguishes between two types of such
      interventions: cause-specific price reductions and cause-specific direct
      provisions. It finds that a cause-specific direct provision always has a positive
      spillover effect on longevity investments for other causes, but a cause-specific
      price reduction may have a negative spillover effect due to a substitution
      effect.

PMID- 17549532
TI  - Pattern visual evoked potentials in Japanese patients with multiple sclerosis
      without history of visual pathway involvement.
AB  - A delay of the peak latency of the pattern visual evoked cortical potentials
      (pVEP) is accepted as one of the paraclinical evidence for a diagnosis of
      multiple sclerosis (MS). The purpose of this study was to evaluate the pVEPs in
      Japanese patients with MS without a history of visual pathway involvement. We
      studied the medical records of 29 MS patients without any history of visual
      pathway involvement, and with visual acuity correctable to > or = 20/20. The
      Goldmann visual fields, pupillary light reflexes, and optic disks were normal in
      all. pVEPs elicited by 3 rev/s (transient) and 12 rev/s (steady-state) were
      recorded from the MS patients and compared with those recorded from normal
      subjects. The latency of the P100 component of the transient pVEPs was
      significantly prolonged in 9/29 (31%) MS patients. A phase lag in the steady
      state pVEPs was found in 6/29 (21%) MS patients, and the mean amplitude was
      significantly smaller. The incidence of cases with abnormal pVEPs is lower than
      that reported from Europe and United State. This difference is possibly due to
      racial differences, and the use of different criteria for diagnosing optic
      neuritis.

PMID- 17549533
TI  - Predicting survival in critical patients by use of body temperature regularity
      measurement based on approximate entropy.
AB  - Body temperature is a classical diagnostic tool for a number of diseases.
      However, it is usually employed as a plain binary classification function
      (febrile or not febrile), and therefore its diagnostic power has not been fully
      developed. In this paper, we describe how body temperature regularity can be used
      for diagnosis. Our proposed methodology is based on obtaining accurate long-term
      temperature recordings at high sampling frequencies and analyzing the temperature
      signal using a regularity metric (approximate entropy). In this study, we
      assessed our methodology using temperature registers acquired from patients with
      multiple organ failure admitted to an intensive care unit. Our results indicate
      there is a correlation between the patient's condition and the regularity of the
      body temperature. This finding enabled us to design a classifier for two outcomes
      (survival or death) and test it on a dataset including 36 subjects. The
      classifier achieved an accuracy of 72%.

PMID- 17549534
TI  - Acute effects of 2 hours of moderate-intensity cycling on serum parathyroid
      hormone and calcium.
AB  - Previous studies have found that serum parathyroid hormone (PTH) increases in
      response to relatively short (<60 minutes), intense bouts of exercise, possibly
      as a result of decreases in serum calcium. Whether longer, less intense exercise
      also stimulates an increase in PTH is not known. The effects of 2 hours of
      moderate-intensity cycling on serum PTH and calcium were investigated in 20
      competitive male cyclists, aged 22-45 years. Serum concentrations of PTH and
      calcium were measured before and after exercise. Dermal calcium loss was
      estimated using patch collections and loss of sweat. There were increases in PTH
      from 40.6 +/- 15.6 to 69.5 +/- 25.5 pg/mL (P < 0.001) and in serum calcium from
      9.3 +/- 0.3 to 9.6 +/- 0.5 mg/dL (mean +/- standard deviation, P = 0.001) in
      response to exercise. Contraction of plasma volume explained the rise in calcium
      but not PTH. Dermal calcium loss was estimated at 138.0 +/- 71.9 mg for the 2
      hour exercise bout. Neither the change in serum calcium nor the dermal calcium
      loss was significantly related to the increase in PTH. The study demonstrated
      that prolonged exercise stimulates PTH secretion. The effects of such transient
      increases in PTH on bone metabolism are not known.

PMID- 17549535
TI  - Growth plate zonal microarray analysis shows upregulation of extracellular matrix
      genes and downregulation of metalloproteinases and cathepsins following
      irradiation.
AB  - Although the growth plate matrix area fraction increases after irradiation,
      extracellular matrix (ECM) gene expression in this context has not been studied.
      The hypothesis was that normally expressed ECM genes would be upregulated after
      irradiation. The right limbs of six Sprague-Dawley 5-week-old rats were
      irradiated with the left limbs as controls. Half of the animals were harvested
      after 1 week and half after 2. Microarray was conducted from normal and
      irradiated tibial growth plate proliferative zone (PZ) and hypertrophic zone (HZ)
      chondrocytes separated by laser microdissection at each time point. In situ
      hybridization (ISH) and real-time polymerase chain reaction (PCR) were used to
      confirm expression of selected genes. At 1 and 2 weeks after irradiation, both
      normally expressed ECM genes and others not highly expressed in the normal growth
      plate showed upregulation. Metalloproteinases and cathepsins were downregulated.
      PZ gene expression after irradiation exhibited features of the normal HZ,
      suggesting premature terminal differentiation. ECM genes not highly expressed in
      the normal growth plate included several members of the small leucine-rich
      proteins and the ezrin-radixin-moesin family. The effects of irradiation on
      cathepsin K (Ctsk), integrin binding sialoprotein (Ibsp), and procollagen II
      alpha 1 (Col2a1), as determined by ISH and real-time PCR, were highly correlated
      with the microarray results. Accumulation of matrix following radiation injury to
      the growth plate correlated well with changes in gene expression. Upregulation of
      genes not normally highly expressed in the noninjured growth plate suggests their
      importance in the injury and repair response.

PMID- 17549536
TI  - Bone mineral density is not sensitive enough to assess the risk of vertebral
      fractures in type 2 diabetic women.
AB  - Although the association between diabetes and osteoporosis has been studied, it
      remains unclear if the pathogenesis of vertebral fractures in patients with type
      2 diabetes would be similar to those without diabetes. One hundred and fifty
      female diabetic patients without apparent proteinuria as well as 716 women
      without diabetes (control group) were examined by lateral thoracic and lumbar
      spine radiographs as well as dual-energy X-ray absorptiometry. Vertebral
      fractures were found in 26 (17.3%) and 158 (22.1%) subjects in the diabetic and
      control groups, respectively. Diabetic patients had higher absolute and age
      matched (Z score) values of lumbar bone mineral density (L-BMD) than controls
      despite their significantly higher mean age. By receiver operating characteristic
      (ROC) analysis, the absolute L-BMD values for detecting vertebral fractures were
      higher and sensitivity and specificity were lower in diabetic patients than
      controls (0.816 g/cm2 vs. 0.716 g/cm2 and 66.0% vs. 74.8%, respectively).
      Logistic regression analysis adjusted for age, body weight, and height also
      showed that L-BMD was not significantly associated with the presence of vertebral
      fractures in diabetic patients (odds ratio [OR] = 0.61, 95% confidence interval
      [CI] 0.34-1.09 per standard deviation increase, P = 0.0954), in contrast to the
      significant association in controls (OR = 0.23, 95% CI 0.16-0.33, P < 0.0001).
      These results show that L-BMD is not sensitive enough to assess the risk of
      vertebral fractures in female diabetic patients and suggest that bone fragility
      not defined by BMD might be related to the risk of vertebral fractures in them.

PMID- 17549537
TI  - Metal content and toxicity of produced formation water (PFW): study of the
      possible effects of the discharge on marine environment.
AB  - A preliminary chemical and ecotoxicological assessment was performed on the
      produced formation water (PFW) and superficial sediment around a gas platform
      (Fratello Cluster), located in the Adriatic Sea (Italy), in order to evaluate the
      effects of PFW discharged from the installation. The ecotoxicological bioassays,
      with the marine bacterium Vibrio fischeri and the sea urchin Paracentrotus
      lividus, were associated with chemical data to estimate the possible effects on
      living organisms. PFW collected on the platform was toxic, but no significant
      effect was recorded on marine sediment. Only the sediment station nearest to the
      discharge point showed higher values of some contaminants (zinc and arsenic) in
      comparison to other sites and only some stations showed low toxicity.

PMID- 17549538
TI  - Increased thyroid hormone levels in tree swallows (Tachycineta bicolor) on
      reclaimed wetlands of the athabasca oil sands.
AB  - The oil sands of Alberta, Canada are one of the world's largest reserves of crude
      oil. Oil sands mining companies are now investigating the ecological impacts of
      reclamation strategies in which wetlands are used for the bioremediation of waste
      materials. To examine the endocrine disrupting potential of chemicals in Oil
      Sands Process Materials (OSPM), thyroid hormone concentrations were measured in
      plasma and thyroid glands of nestling tree swallows (Tachycineta bicolor) from
      wetlands partly filled with mine tailings. Plasma triiodothyronine (T(3))
      concentrations and thyroxine (T(4)) content within thyroid glands were elevated
      in nestlings from OSPM sites compared to those from the reference site. Results
      suggested enhanced hormone synthesis by the thyroid glands independently of
      activation of the pituitary-thyroid axis, as well as increased deiodination of
      T(4) into T(3) in peripheral tissues. This might have resulted from exposure to
      oil sands associated chemicals such as polycyclic aromatic hydrocarbons and from
      environmental factors such as food availability. Modulation of thyroid function
      might have negative effects on metabolism, behavior, feather development, and
      molt, which could compromise postfledging survival.

PMID- 17549539
TI  - Heavy metals in aquatic macrophytes from two small rivers polluted by urban,
      agricultural and textile industry sewages SW Poland.
AB  - This article presents the results from a study of the comparison of 2 lowland
      rivers: the Olobok and the Pilawa in southwest Poland polluted by urban,
      agricultural, and textile industry sewages. pH and concentrations of Ca, Cd, Co,
      Cr, Cu, Fe, K, Mg, Mn, Ni, Pb, Zn, nitrate, nitrite, ammonia, phosphate, and
      sulfate were measured in water samples and concentrations of Ca, Cd, Co, Cr, Cu,
      Fe, K, Mg, Mn, N, Na, Ni, P, Pb, S, and Zn were measured in stream bottom
      sediments and in the aquatic macrophytes Elodea canadensis, Callitriche verna,
      Potamogeton crispus, Potamogeton natans, and Ceratophyllum demersum from the
      river Olobok and Elodea canadensis, Polygonum amphibium, Potamogeton crispus, and
      Veronica beccabunga from the river Pilawa. The matrix of concentrations of 16
      elements in 27 plant samples of 7 species from 15 sampling sites of 2 rivers and
      concentrations of 15 elements and pH in water samples and 16 elements and pH in
      bottom sediment samples of these sites was submitted to numerical classification,
      which revealed that sampling sites from the rivers were differentiated by the
      value of factor 1 of principal component analysis (PCA), which was related to the
      pH of water, Ca, Cu, Mg, Mn, and Ni in water and Cd, Cr, Cu, Fe, K, Mg, Na, Ni,
      P, and S in bottom sediments. More polluted parts of both rivers were
      differentiated from less polluted parts by the value of factor 2 of PCA, which
      was related to Pb, Zn, and sulfates in water and Ca and Zn in bottom sediments.
      Macrophytes from the Olobok and Pilawa rivers were differentiated by the value of
      factor 1, which was related to Ca, Co, Cr, Cu, Fe, Mg, Ni, N, Na, Pb, and S.
      Groups of macrophytes of more and less polluted parts of both rivers differed by
      the value of factor 2, which was related to P, K, and Mn. Downstream of the
      sewage outputs in both rivers, a significantly increased level of pollution
      occurs with elements correlated with factor 1: Among others were Cu and Cr,
      typical for the textile industry along the river Pilawa, and among others were Mn
      and Ni, typical for the urban and agricultural activities in the river Olobok.

PMID- 17549540
TI  - Waterborne amitrole affects the predator-prey relationship between common frog
      tadpoles (Rana temporaria) and larval spotted salamander (Salamandra salamandra).
AB  - Within their aquatic habitats, larval amphibians are often subjected to multiple
      natural and anthropic stressors. Among these, predation and waterborne pollution
      represent two types of stressing factor that frequently co-occur. In this
      connection, the present laboratory study was designed to investigate the effects
      of amitrole, a commonly used triazole herbicide, on the predator-prey
      relationship between common frog tadpoles (Rana temporaria) and larval spotted
      salamander (Salamandra salamandra). Tadpoles were exposed for 3 days to 0, 0.01,
      0.1, 1, and 10 mg/L amitrole, either in the absence or in the presence of larval
      salamanders. Tadpole behavior (refuge use, movements) was monitored every day,
      and the predation efficiency was assessed at the end of the experiment by
      counting the number of surviving tadpoles. In the absence of the predator,
      amitrole-exposed tadpoles (at 0.01, 0.1, and 1 mg/L) increased their refuge use
      and decreased their rate of movements. In the presence of the predator, amitrole
      contamination did not affect tadpole behavior, except on the first day, where
      tadpoles exposed to 10 mg/L were found to be significantly more active than
      unexposed control tadpoles. Throughout the experiment, control tadpoles were the
      only group to show significant reductions of activity and visibility in response
      to the predator's presence. In contrast, tadpoles exposed to 0.01 and 0.1 mg/L
      amitrole increased their refuge use in response to the predator, whereas their
      rate of movements remained unaffected. Furthermore, exposures of tadpoles to the
      two highest amitrole concentrations (1 and 10 mg/L) resulted in the loss of both
      behavioral responses to the predator's presence. Interestingly, the lack of
      antipredator behavior in amitrole-exposed tadpoles did not enhance their
      vulnerability to predation by the larval salamander. Moreover, tadpoles exposed
      to the two highest herbicide concentrations showed a better survival than
      unexposed controls, indicating that amitrole contamination also had detrimental
      effects on the predatory behavior of the larval salamander. These findings
      emphasize the need to consider the effects of contaminants on both predator and
      prey before drawing conclusions about the possible consequences of prey
      behavioral modifications on the predation risk.

PMID- 17549541
TI  - Toxicity of organophosphates on morphology and locomotor behavior in brine
      shrimp, Artemia salina.
AB  - The acute toxicity and hatching success of four organophosphorus insecticides-
      acephate (ACEP), chlorpyrifos (CPP), monocrotophos (MCP), and profenofos (PF)-
      was studied in a short-term bioassay using brine shrimp, Artemia salina. Fifty
      percent hatchability inhibition concentration and median lethal concentration
      (LC(50)) values were calculated after probit transformation of the resulting
      data. Among the insecticides tested, CPP is found to be the most toxic and also
      to inhibit hatching success of A. salina cysts in a concentration-dependent
      manner. In addition, the effect of these pesticides on locomotor behavior
      (swimming speed) and morphologic differences were studied in LC(50)-exposed
      nauplii after 24 hours. The in vivo effect of these insecticides on
      acetylcholinesterase (Enzyme commission number (EC 3.1.1.7) activity was also
      determined in LC(50)-exposed nauplii after 24 hours. Maximum percent decrease in
      their swimming speed and significant morphologic alterations were noticed in CPP
      exposed brine shrimps. The order of toxicity was CPP > PF > MCP > ACEP in all the
      parameters studied.

PMID- 17549542
TI  - Effects of injection systems and plastic mulches on distribution and emissions of
      cis- and trans-1,3-dichloropropene and chloropicrin.
AB  - The concentration and distribution of a soil fumigant in the subsurface of field
      plots are two key factors in the determination of the fumigant efficacy.
      Subsurface concentrations of the biologically active compounds cis- and trans-1,3
      dichloropropene (1,3-D) and chloropicrin (CP) were determined in soil at two
      adjacent injection traces and midpoint between the two traces in plastic-covered
      field beds after injection of the fumigant Telone C35 by conventional chisels or
      by a coulter rig (Avenger coulters). Two of the four beds were covered with
      metallic polyethylene film (MPE) and the remaining two were covered with
      virtually impermeable film (VIF). Three hours after chisel injection,
      concentrations of the three compounds at the two adjacent injection traces in the
      two beds were highly variable. Large concentrations of the compounds were
      detected at the side traces, whereas the compounds were not detected at the
      middle traces (bed centers) in the two chisel-injected beds covered with MPE or
      VIF. Initial concentrations of the three compounds at the two adjacent injection
      traces in the two Avenger-coulter-injected beds were more uniform than in the
      chisel-injected beds but still variable. Also, the three compounds had diffused
      horizontally to midpoint between the two injection traces in all four beds,
      generally in smaller concentrations. Concentrations of the three compounds in the
      shallow subsurface soil layer (0.5-30 cm) in the beds became progressively more
      uniform and then declined slowly. Volatilization losses from the two Avenger
      coulter-injected beds and the chisel-injected bed covered with VIF were low.
      Combination of Avenger coulter injection and VIF provided better retention of the
      compounds in this soil layer and, thus, likely would provide better fumigant
      efficacy and crop yield.

PMID- 17549543
TI  - Aquatic toxicity of leachates generated from electronic devices.
AB  - Heavy metal leaching of electronic waste has been documented in recent
      literature. Heavy metal aquatic toxicity in the toxicity characteristic (TC)
      leachates produced from 56 electronic devices were tested using the aquatic
      toxicity assays such as Ceriodaphnia dubia 48-hr acute toxicity assay, the
      Selenatastrum capricornutum chronic algal growth inhibition assay (test used only
      for circuit-board leachates), and the MetPLATE acute heavy metal toxicity tests.
      The electronic devices tested, include 9 circuit boards (printed wire boards), 2
      videocassette recorders, 4 remote controls, 1 cathode ray tube, 15 cellular
      phones, 1 calculator, 5 smoke detectors and their PC board components, 3
      printers, 4 laptop computers, and 7 personal computer central processing units
      (CPUs). The toxicity tests showed toxicity in 51 of the 56 Toxicity
      Characteristic Leaching Procedure leachates of electronic devices assayed.

PMID- 17549544
TI  - The effects of the fungicide methyl thiophanate on adrenal gland morphophysiology
      of the lizard, Podarcis sicula.
AB  - Endocrine-disrupting chemicals (EDCs) are a large group of substances able to
      modulate endocrine-signaling pathways, altering the normal function of the
      endocrine system. Although the fungicide methyl thiophanate (MT) is not
      considering a specific reproductive and developmental toxicant, it can induce
      histopathological damages in rat thyroid and adrenal glands that have a pivotal
      role in both processes. We investigated the MT effects on adrenal glands of
      Podarcis sicula lizard, the endemic species of Southern Italy living in open
      country and in cultivated fields. Reptiles are good bioindicators because they
      are easily harvested; they have a wide distribution and large populations.
      Moreover, they have good sensitivity to contaminants, and bioaccumulate and
      biomagnify pollutants to levels equal to or greater than those of birds and
      mammals. We used 1.5% MT/water to pollute terraria, food, and water twice a week
      for 15 and 30 days, and we evaluated adrenal toxicity through biochemical
      (adrenal and pituitary hormone plasma levels) and histological parameters
      (adrenal gland histopathology). We demonstrated a time-dependent increase of
      corticosterone plasma levels and a decrease of ACTH plasma levels, a hypertrophy
      of the steroidogenic tissue, and an enlargement of blood capillaries. Moreover,
      we observed a time-dependent increase of adrenaline plasma levels and adrenaline
      producing cells, and an opposite trend of noradrenaline plasma concentrations. We
      also observed lymphocyte and macrophage infiltrations, signs of cell
      degeneration. Our findings on the bioindicator P. sicula provide an interesting
      basis to further elucidate the systemic mechanisms of EDCs.

PMID- 17549545
TI  - Assessment of diazinon toxicity in sediment and water of constructed wetlands
      using deployed Corbicula fluminea and laboratory testing.
AB  - Constructed wetlands for mitigation of nonpoint agricultural runoff have been
      assessed for their ability to decrease potential toxicity from associated
      contaminants. After a simulated runoff event, constructed wetlands positioned in
      series were used to measure the effects of the organophosphate insecticide
      diazinon. Water, sediment, and plant samples from five sites were analyzed for
      diazinon concentrations from 0.5 hours to 26 days; peak concentrations were
      measured in sediment after 0.5 hours (268.7 microg/kg) and in water and plant
      tissue after 3 hours (121.71 microg/L and 300.7 microg/kg, respectively).
      Cholinesterase activity and changes in shell growth were measured from Corbicula
      fluminea deployed at corresponding sites. Water collected after 9 hours from all
      wetland sites contained diazinon concentrations sufficient to cause toxicity to
      Ceriodaphnia dubia, but not to Pimephales promelas. C. dubia survival was
      decreased in water sampled through 7 days from the site nearest runoff
      introduction, whereas C. fluminea deployed at this same site experienced 100%
      mortality after 26 days. Clams from lower sites survived wetland conditions, but
      growth and ChE activity were significantly decreased lower than that of clams
      from a control site. C. dubia exposed to water from these sites continued to have
      decreased survival throughout the 26-day sampling. Sediment sampled from 48 hours
      through 14 days at the lowest wetland site decreased the laboratory survival of
      Chironomus dilutus, and sediment from upper sites elicited an effect only on day
      26. Although wetland concentrations of aqueous diazinon were decreased lower than
      toxic thresholds after 26 days, decreased ChE activity in deployed clams provided
      evidence of residual diazinon effects to deployed organisms.

PMID- 17549546
TI  - PCB levels and accumulation patterns in waterbird eggs and in their prey at Lake
      Kerkini, a north-eastern Mediterranean wetland of international importance.
AB  - Seven "target" PCB levels were determined and compared in waterbird eggs, in
      their prey, and in water at Lake Kerkini, northern Greece, to investigate PCB
      bioaccumulation patterns and to define the best bioindicator of target PCBs for
      this area. PCBs were analysed from eggs of Phalacrocorax carbo, Podiceps
      cristatus, Ardea cinerea, Egretta garzetta, and Nycticorax nycticorax and from
      prey types Alburnus alburnus, Rutilus rutilus, Lepomis gibbosus. Carassius
      auratus, and Rana sp. PCBs analysed were detected in all bird eggs, prey, and
      water but contamination patterns differed among these sample types. The lipid
      corrected geometric means of the congeners analysed were significantly different
      among most bird species and among some prey species. PCB congeners 118, 138, 153,
      and 180 accounted for around 80% of the total PCB contamination in bird egg
      samples. Percent congener concentrations of high-chlorinated PCBs tended to
      increase from water through prey to most bird egg samples whereas the low
      chlorinated PCBs (28 and 52) decreased. Bioaccumulation factors (BAFs) also
      exhibited an increasing trend for higher chlorinated PCBs from prey types to bird
      eggs. The greatest BAFs of six of the congeners were shared between Phalacrocorax
      carbo and Ardea cinerea. Among prey, the BAFs of four PCBs were highest in
      Lepomis gibbosus. Biomagnification factors varied between 1.01 and 39.57. In
      contrast to low chlorinated PCBs, high chlorinated congeners biomagnified
      considerably through fish prey. The highest biomagnification took place in
      Phalacrocorax carbo. No relationship was found between the lipid content of
      samples and BAFs of PCBs probably due to biotransformation differences of the
      congeners in the biota sampled. Due to the greatest PCB concentrations especially
      of the higher chlorinated PCBs in the eggs of Phalacrocorax carbo and its
      considerable bioaccumulation tendencies, it is proposed as the best PCB
      biomonitor of target PCBs at Lake Kerkini. Lepomis gibbosus had the highest
      concentrations of most congeners and exhibited the greatest bioaccumulative
      properties among prey and can be used as an alternative biomonitor.

PMID- 17549547
TI  - The presence and impact of environmental lead in passerine birds along an urban
      to rural land use gradient.
AB  - Contamination of wetlands by lead shot and lead fishing weights has generated a
      tremendous amount of research into the impact of lead poisoning on wildlife. Less
      well known are the potential threats to wildlife posed by lead contaminants still
      prevalent in urban environments. Despite a U.S. federal ban on lead-based paint
      and gasoline in 1978 and 1986, respectively, lead residue is still prevalent at
      hazardous levels in urban and suburban environments and may present a health
      concern for people and wildlife, particularly birds. We quantified soil lead
      content in residential properties across a rural-to-urban land-use gradient in
      the metropolitan Washington, D.C. area and then assessed the impact of lead
      contamination on body condition in adult and nestling passerine birds at the same
      sites. Soil lead concentration was significantly higher in urban sites compared
      to rural sites. Accordingly, adult and nestling birds captured in urban sites had
      significantly higher blood lead concentrations than their rural counterparts.
      However, only gray catbird nestlings exhibited lower body condition as a result
      of lead contamination. Birds continue to breed in urban habitats despite numerous
      negative attributes to these environments including light, noise, pedestrian and
      toxic contaminants, such as lead. These sites often contain habitat that appears
      suitable for roosting, nesting, and foraging and thus may act as an ecological
      trap for breeding birds because breeding success is often negatively associated
      with increasing urbanization. Lead contamination is one more feature of
      urbanization that birds and other wildlife must face in an increasingly developed
      world.

PMID- 17549548
TI  - Developing toxicity scores for embryotoxicity tests on elutriates with the sea
      urchin Paracentrotus lividus, the oyster Crassostrea gigas, and the mussel
      Mytilus galloprovincialis.
AB  - Bioassays are routinely employed for sediment quality assessment. In order to be
      able to effectively use Bioassays responses in regulatory and management
      frameworks, toxicity scores, which rank toxicity data in defined classes that are
      continuous and difficult to interpret, should be reliable and suitable tools to
      support decisions about the presence or absence of toxicity in tested samples and
      on how toxic a sample is. A statistical approach is needed to define thresholds
      for toxicity scores. The Minimum Significance Difference (MSD) criterion allowed
      the evaluation of toxicity thresholds for each test-matrix and organism pair,
      based on large sets of experimental data. The MSD values were normalized with
      respect to the control, ranked in ascending order, and the 90th percentile was
      identified; the Toxicity Threshold (TT) was calculated by subtracting the 90th
      percentile from 100 and the Toxicity Limit (TL) was estimated as the percentage
      of control response multiplied by TT. Taking into account sample responses
      normalized with respect to control (S), when S > TL, the sample is considered
      nontoxic; when S <or= TL, toxicity is statistically present. The MSD criterion
      was applied on a dataset of results from both published and ongoing projects
      using the validated embryotoxicity tests with the echinoid Paracentrotus lividus,
      the oyster Crassostrea gigas, and the mussel Mytilus galloprovincialis, on
      elutriates from sediments of the Venice Lagoon. Once the threshold defining
      presence or absence of toxicity had been calculated, four other toxicity classes
      were developed: low (for toxicity data expressed as percentage of effect),
      medium, high, and very high toxicity (for toxicity data expressed as TU50).

PMID- 17549549
TI  - Recent sedimentary history of organic matter and nutrient accumulation in the
      Ohuira Lagoon, northwestern Mexico.
AB  - (210)Pb-derived sediment accumulation rates, as well as a suite of geochemical
      proxies (Al, Fe, delta(13)C, delta(15)N), were used to assess the time-dependent
      variations of C, N, and P fluxes recorded in two sediment cores collected at
      Ohuira Lagoon, in the Gulf of California, Mexico, during the last 100 years.
      Sedimentary C, N, and P concentrations increased with time and were related to
      land clearing, water impoundment, and agriculture practices, such as
      fertilization. C:N:P ratios and delta(13)C suggested an estuarine system that is
      responsive to increased C loading from a N-limited phytoplankton community,
      whereas delta(15)N values showed the transition between an estuarine-terrestrial
      to an estuarine-more marine environment, as a consequence of the declining
      freshwater supply into the estuary due to the channeling and impoundment of El
      Fuerte River between 1900 and 1956. The recent increases in nutrient fluxes (2-
      to 9-fold the pre-anthropogenic fluxes of C and N, and 2 to 13 times for P)
      taking place in the mainland from the 1940s, were related to the expansion of the
      intensive agriculture fields and to the more recent development of shrimp farming
      activities.

PMID- 17549550
TI  - Thermal and biocidal (chlorine) effects on select freshwater plankton.
AB  - Impact of select levels of temperature, individually and in combination, with
      different initial chlorine concentrations on the growth and reproduction of
      phytoplankter Chlorella vulgaris and zooplankton C. reticulata, C. viridis, and
      Diaptomus forbesi was evaluated. During the experiment, optimum growth
      temperature for the alga was estimated as 26 degrees C, even though alga showed
      considerable growth up to 36 degrees C. However, initial chlorine at
      concentrations >or=0.25 mg l(-1) adversely affected growth (P < 0.05 to 0.001) at
      all select temperature levels (26 degrees C, 31 degrees C, 33 degrees C, 36
      degrees C, 39 degrees C, 42 degrees C, and 45 degrees C). Investigations toward
      effects of different temperatures (26 degrees C, 31 degrees C, 33 degrees C, and
      36 degrees C) on zooplankton indicated that survivability of these organisms was
      affected at temperatures >or=33 degrees C. However, the percent growth rates of
      zooplankters at 26 degrees C were significantly higher (P < 0.05) than those at
      31 degrees C, 33 degrees C, and 36 degrees C. Initial chlorine levels of 0.5 and
      0.25 mg l(-1) were lethal to zooplankton; however, zooplankton survival was not
      affected at 0.06 mg l(-1) chlorinated water at all selected temperatures.

PMID- 17549551
TI  - Coaccumulation of cadmium and zinc in tissues of sentinel mallards (Anas
      platyrhynchos) using a former dredge-disposal impoundment.
AB  - Six- to eight-month-old female farm-raised mallards (Anas platyrhynchos) were
      used to examine the accumulation of and association among cadmium (Cd), zinc
      (Zn), and copper (Cu) from an impoundment constructed to contain sediments
      dredged from a lake contaminated by a zinc smelter. Cd was not detectable in the
      livers t of farm-raised mallards (day 0), although sentinel mallards accumulated
      hepatic Cd in the first 7 days after release. By day 14, mean concentrations of
      Cd in kidneys (= 2.82 mg/kg wet weight) had increased 3.4-fold. The mean
      pancreatic Cd concentration increased 59% between days 7 and 14. Renal Zn
      increased nominally, whereas pancreatic Zn increased 63% in sentinel ducks after
      release. Hepatic Zn increased significantly in the first week of release. Renal
      and pancreatic Cu concentrations did not change significantly, whereas
      concentrations of Cu in livers of ducks increased 50% in the 7 days after release
      before decreasing by nearly the same degree. Concentrations of Cd and Zn were
      correlated in livers of sentinel mallards on days 7 and 14. Cd and Cu were not
      correlated in the tissues of any cohort. Cu and Zn were correlated in the livers
      of farm-raised mallards, in the pancreases of sentinel mallards at day 7, and in
      the kidneys of the ducks in all three treatments. The relationship between Cd and
      Zn in tissues of ducks in our study was complicated by simultaneous exposure to
      increased and heterogeneous concentrations of Cd and Zn, both of which can induce
      metallothionein and compete for this and other ligands.

PMID- 17549552
TI  - Decreased acne symptoms as a perception of rhinoplasty success.

PMID- 17549553
TI  - The use of expanded polytetrafluoroethylene (Gore-Tex) in rhinoplasty.
AB  - BACKGROUND: Septal cartilage still is the most appropriate graft material used in
      rhinoplasty. In traumatic or revision cases, septal cartilage can be
      insufficient, and the need for an implant material emerges. In this study, the
      safety and efficacy of polytetrafluoroethylene (Gore-Tex) used as an implant
      material in nasal dorsal augmentation were assessed. METHODS: This study
      retrospectively reviewed 74 patients who underwent nasal dorsal augmentation with
      Gore-Tex. Of the 74 patients who underwent rhinoplasty with Gore-Tex for dorsal
      augmentation from February 1999 to January 2006, 46 (62.2%) represented primary
      cases and 28 (37.8%) represented revision cases. The patients were followed from
      5 to 62 months (average, 28 months) and questioned about cosmetic and functional
      outcomes. The results were assessed according to patients' charts as well as
      preoperative and postoperative photographic documentation. RESULTS: There were no
      complications such as infections, foreign body reaction, extrusions, resorption,
      or migration, and all the patients were satisfied with their results. Only one
      case of soft tissue reaction was observed, which lasted for 3 weeks
      postoperatively. CONCLUSIONS: Biocompatibility, ease of use, lack of extrusion or
      resorption, and low rate of infection make Gore-Tex a good alternative to
      autogenous tissue. However, long-term success and complication rates still are
      lacking, and large numbers of patients with longer follow-up periods are
      required.

PMID- 17549554
TI  - Vertical scar with the bipedicle technique: a modified procedure for breast
      reduction and mastopexy.
AB  - BACKGROUND: Reduction mammaplasty and mastopexy are commonly performed aesthetic
      procedures. One such procedure, the vertical scar technique, has gained
      popularity in recent years, and various types of pedicles have been designed and
      associated with it. The vertical scar with the bipedicle technique is one such
      combination that ensures nipple safety and minimizes scarring, with a good
      aesthetic result. METHOD: With the vertical scar marked on the outside and the
      bipedicle flap marked on the inside, the procedure was performed for 23 patients.
      RESULTS: Between 2004 and 2006, 17 reduction mammoplasties and 6 mastopexies were
      performed. The average tissue resection was 360 g, and the average blood loss was
      70 g. The average preoperative nipple-areolar complex was 28 cm (range, 23-41
      cm). Good results were achieved for the majority of the patients, with no nipple
      loss or loss of sensation. CONCLUSION: The vertical scar bipedicle technique, a
      combination that meets the requirement of minimum scarring and a robust blood
      supply to the nipple-areolar complex, is a suitable option for selected reduction
      mammaplasty and mastopexy.

PMID- 17549555
TI  - Anthropometry of the normal human auricle: a study of adult Indian men.
AB  - BACKGROUND: To treat auricular deformities or to perform facial rejuvenation, a
      plastic surgeon requires normative data for auricular dimensions. The metric
      standards vary in various ethnic groups, and such data are especially scarce from
      in India. This study aimed to provide anthropometric information about the normal
      dimensions of the adult male auricle in central India. METHODS: A cross-sectional
      study was undertaken in central India with 415 males categorized in five age
      groups. Six linear dimensions including the length and width of the auricle,
      lobule, and concha and the heights of the auricular protrusion at the superaurale
      and tragal levels were measured. Auricular, lobular, and conchal indices were
      calculated. The inclination of the auricle relative to its vertical axis was
      measured. Descriptions of various auricle parts including its shape, preauricular
      area, form of the helical fold, lobular shape, size, and type of attachment to
      the cheek were recorded. RESULTS: Almost all the linear measurements showed a
      steady increase in size with age. The dimensions of the lobule were dependent on
      its shape and attachment to the cheek. The mean lobular and auricular indices
      were found to decrease with increasing age, indicating more elongation than
      widening of the structures. On the average, bilateral asymmetry was observed in
      all measurements, although only auricular length, width, and conchal length in a
      few age groups were found to be statistically significant. The frequency
      distribution of forms of various auricular features is presented. CONCLUSION: The
      human ear continues to grow throughout life. The lobule contributes the most to
      the overall elongation of the auricle. This study furnishes the first set of
      metric data of auricular dimensions for normal Indian males 18 to 70 years of
      age. In comparison with other ethnic groups, Indian males seem to have the
      smallest auricular and lobular lengths, although their respective widths are
      comparable with those of others.

PMID- 17549556
TI  - Re: implications of transaxillary breast augmentation: lifetime probability for
      the development of breast cancer and sentinel node mapping interference.

PMID- 17549557
TI  - A new simple technique for making facial dimples.
AB  - In Asia, especially in China, women think a dimple is an important part of a
      beautiful smiling face. The dimple can make them more confident. Unfortunately,
      not all women have dimples. Hence, with the development of the Chinese economy,
      there is an increasing demand among Chinese women for the creation of dimples.
      Most women hope the impairment of the operation will be slight and the period of
      recovery short so they can go to work as quickly as possible. Some of them want
      to have dimples only when they smile. The authors have used a new simple
      technique to form 56 dimples for 36 women. During the operation, they use a
      syringe needle to guide a monofilament nylon suture through the dermis and the
      active facial muscles (usually the buccinator). A sling is formed between the
      skin and the buccinator muscle. The knot is tied, and the dimple is created.
      After the operation, patients have been satisfied with the shape of the dimples.
      Furthermore, hematoma and infection never occurred. As a result, on the basis of
      their experience, the authors conclude that this technique is simple and easy to
      duplicate. Moreover, this technique has many benefits. For example, with this
      procedure, it is easy to adjust the bulk of dimples by adjusting the tension of
      the knot and the amount of dermis tissue the injection needle sutures. Because no
      tissue is resected, there is mild postoperative swelling. Consequently, patients
      can return to work or other activities 2 days after the operation.

PMID- 17549558
TI  - Sliding osteotomy genioplasty for facial aesthetic balance: 10 years of
      experience.
AB  - The chin, one of the most obvious facial structures, plays an important role in
      the perception of the face as an instrument of communication. To alter the chin
      contour in a reliable manner, horizontal sliding osteotomy of the mandibular
      symphysis with advancement of the mobilized segment is the technique of choice
      for correction of the anterior posterior deficiency. This study describes
      surgical techniques used in aesthetic and functional surgery of the chin as well
      as the outcomes. Over a 10-year period, 474 patients underwent orthognathic
      surgery for correction of their malocclusion. Of these 474 patients, 155 were
      treated in combination with a sliding genioplasty (SGP) and 37 (29 women and 8
      men; average age, 32 years; range, 18-47 years) had an isolated SGP. Of these
      patients, 33 had chin advancement and 4 had chin reduction. The mean chin
      advancement was a modest 4.5 mm (range, 2-7 mm), and the mean chin vertical
      displacement was 3.9 mm (range, 2.5-4.1 mm). All the patients in the mandibular
      deficiency group had a residual sagittal disproportion of the progonion relative
      to the subnasale (mean, -7.6 mm) and a newly created vertical disproportion, with
      mean lower face heights of 67.8 mm compared with mean midface heights of 65.3 mm.
      The surgical outcome was evaluated by analysis of pre- and postoperative
      photographs, analysis of pre- and postoperative measurements, and patients' self
      judgment. All the patients healed uneventfully without any major postoperative
      problems. Paraesthesia of the mental nerves occurs to some degree in almost all
      patients measured by the Simmon Weinstein diagnostic device. In the single
      sliding chin osteotomy group, no major branches of the mental nerves were
      transacted. Paraesthesia was only transient, usually lasting for only a few
      weeks. At least 1 year after the operation, normal sensitivity of the lower lip
      and both sides of the chin was reported by almost all of the patients (93.1%).
      All who had only a single genioplasty recovered totally from a neurosensory
      deficit. The level of satisfaction was significantly high for all the patients.
      The results were judged to be excellent in 73.2% and good in 23.6% of the cases.
      Only in 3.2% of the cases was it considered to be poor (bimaxillary surgery
      combined with SGP). The current findings strongly suggest that SGP is a reliable
      procedure for achieving harmony of the lower face. In addition, it permits a
      simplification of facial reconstruction and rejuvenation. The combination of chin
      advancement and submental recontouring can have a positive effect on facial
      appearance, provided the increased chin projection is appropriate.

PMID- 17549559
TI  - Implications of transaxillary breast augmentation: lifetime probability of breast
      cancer development and sentinel node mapping interference.
AB  - After the "fifth-generation" breast implants with ultracohesive silicone gel
      technology are introduced, the Food and Drug Administration (FDA) will sooner or
      later retire the ban on the use of these devices in the United States. When this
      happens, the plastic surgery community must be prepared to face a massive demand
      for reoperations to change saline-filled breast implants because cohesive gel
      devices have the potential to provide a more natural breast shape, to minimize
      the risk of postoperative rippling, and to provide a greater degree of safety if
      the implant loses its integrity. Despite these advantages and extensive use
      throughout the rest of the world during the ban in the United States, silicone
      implants also have disadvantages. One drawback is that transaxillary breast
      augmentation with more "rigid" gel-filled implants may produce trauma to the
      armpit, may interfere with sentinel node mapping for breast cancer treatment, and
      may have future medicolegal implications.

PMID- 17549560
TI  - The fate of diced cartilage grafts of traumatized versus nontraumatized origin.
AB  - BACKGROUND: Diced cartilage grafts have long been used in rhinoplasty. Along with
      their various reported advantages, they also have some disadvantages. The
      irregular resorption rate of the engrafted mass is one of the major issues noted
      with diced cartilage grafts. An explanation for the unpredictable resorption rate
      has not yet been elucidated. This study aimed to determine the role of
      traumatized versus nontraumatized cartilage as the source of diced cartilage
      grafts. METHODS: This study included the noses of 32 patients (19 traumatized
      noses and 13 nontraumatized noses) who underwent surgery using Surgicel-wrapped
      diced cartilage grafts. RESULTS: The most remarkable result noted in this study
      was that a Surgicel-wrapped diced cartilage graft, if prepared from traumatized
      cartilage (in 19 patients), failed to maintain a stable long-term volume. Partial
      volume loss was noted in 100% of these patients. However, the rate of this
      partial resorption was different for every individual and could not be predicted.
      The highest retention of cartilage graft volume was seen primarily over the nasal
      osseocartilaginous junction. In nontraumatized patients, however, the engrafted
      mass maintained long-term volume stability. These patients evidenced no visible
      external irregularities, and only a few very slight imperfections were noted with
      finger palpation. CONCLUSION: Diced cartilage of traumatic origin is not
      recommended for any purpose. In such cases, the authors' engrafting algorithm
      consists of autobone or ear conchal cartilage grafts for dorsal augmentation,
      columellar struts from the nontraumatized part of the septum, and spreader grafts
      from the nontraumatized part of the septum or ear concha.

PMID- 17549561
TI  - Skin nodules after semipermanent cosmetic dermal filler.
AB  - The authors present what they believe is only the third reported incidence of
      orofacial granulomas after injection of semipermanent cosmetic filler.

PMID- 17549562
TI  - Replacement of buried cysteine from zebrafish Cu/Zn superoxide dismutase and
      enhancement of its stability via site-directed mutagenesis.
AB  - Zebrafish Cu/Zn-superoxide dismutase (ZSOD1) has one free cysteine (Cys-7) in a
      first beta-strand with lower thermostability. We predicted the stability would be
      increased with single-point mutation at 70 degrees C via the I-Mutant 2.0 server,
      and generated a mutant SOD with replacement of the free Cys to Ala (ZSODC7A) by
      site-directed mutagenesis. The mutant was expressed and purified from the
      Escherichia coli strain AD494(DE3)pLysS and the yield was 2 mg from 0.4 L of
      culture. The ZSODC7A was heated at 90 degrees C. In a time-dependent assay, the
      time interval for 50% inactivation was 32 min, and its thermal inactivation rate
      constant K (d) was 2 x 10(-2) min(-1). The mutant was still activated in broad pH
      range (2.3-12), and had only a moderate effect under sodium dodecyl sulfate
      treatment. The calculated specific activity of the mutant was 3980 U/mg, twice
      that of wild-type ZSOD1. In addition, we soaked fish larva with equal enzyme
      units of either ZSOD1 or ZSODC7A for 2 h, and then stressed them with 100 ppm of
      paraquat to induce oxidative injury. The survival rate was significant.

PMID- 17549563
TI  - Mitochondrial DNA diversity of the Asian moon scallop, Amusium pleuronectes
      (Pectinidae), in Thailand.
AB  - Sequence variation of the mitochondrial DNA 16S rRNA region of the Asian moon
      scallop, Amusium pleuronectes, was surveyed in seven populations along the coast
      of Thailand. A total of 16 unique haplotypes were detected among 174 individuals
      with a total 27 variable sites out of 534 bp sequenced. The mitochondrial
      haplotypes grouped into two distinct arrays (estimated to differ by about 2.62%
      to 2.99% nucleotide divergence) that characterized samples collected from the
      Gulf of Thailand versus the Andaman Sea. Low levels of intrapopulation variation
      were observed, while in contrast, significant divergence was observed between
      populations from the Gulf of Thailand and Andaman Sea. Results of AMOVA reveal a
      high F (ST) value (0.765) and showed that the majority of the total genetic
      variance (76.03%) occurred among groups (i.e., Andaman Sea and the Gulf of
      Thailand) and little among populations within the group (0.52%) and within
      populations (23.45%). The genetic differentiation between the populations
      recorded in the present study is similar to that observed in a variety of marine
      species in the Indo-Pacific. The implications of the findings for management of
      A. pleuronectes genetic resources in Thailand are discussed.

PMID- 17549564
TI  - Acceptance test of a commercially available software for automatic image
      registration of computed tomography (CT), magnetic resonance imaging (MRI) and
      99mTc-methoxyisobutylisonitrile (MIBI) single-photon emission computed tomography
      (SPECT) brain images.
AB  - This note describes a method to characterize the performances of image fusion
      software (Syntegra) with respect to accuracy and robustness. Computed tomography
      (CT), magnetic resonance imaging (MRI), and single-photon emission computed
      tomography (SPECT) studies were acquired from two phantoms and 10 patients. Image
      registration was performed independently by two couples composed of one
      radiotherapist and one physicist by means of superposition of anatomic landmarks.
      Each couple performed jointly and saved the registration. The two solutions were
      averaged to obtain the gold standard registration. A new set of estimators was
      defined to identify translation and rotation errors in the coordinate axes,
      independently from point position in image field of view (FOV). Algorithms
      evaluated were local correlation (LC) for CT-MRI, normalized mutual information
      (MI) for CT-MRI, and CT-SPECT registrations. To evaluate accuracy, estimator
      values were compared to limiting values for the algorithms employed, both in
      phantoms and in patients. To evaluate robustness, different alignments between
      images taken from a sample patient were produced and registration errors
      determined. LC algorithm resulted accurate in CT-MRI registrations in phantoms,
      but exceeded limiting values in 3 of 10 patients. MI algorithm resulted accurate
      in CT-MRI and CT-SPECT registrations in phantoms; limiting values were exceeded
      in one case in CT-MRI and never reached in CT-SPECT registrations. Thus, the
      evaluation of robustness was restricted to the algorithm of MI both for CT-MRI
      and CT-SPECT registrations. The algorithm of MI proved to be robust: limiting
      values were not exceeded with translation perturbations up to 2.5 cm, rotation
      perturbations up to 10 degrees and roto-translational perturbation up to 3 cm and
      5 degrees.

PMID- 17549565
TI  - Effects of root isoquinoline alkaloids from Hydrastis canadensis on Fusarium
      oxysporum isolated from Hydrastis root tissue.
AB  - Goldenseal (Hydrastis canadensis L.) is a popular medicinal plant distributed
      widely in North America. The rhizome, rootlets, and root hairs produce
      medicinally active alkaloids. Berberine, one of the Hydrastis alkaloids, has
      shown antifungal activity. The influence of a combination of the major Hydrastis
      alkaloids on the plant rhizosphere fungal ecology has not been investigated. A
      bioassay was developed to study the effect of goldenseal isoquinoline alkaloids
      on three Fusarium isolates, including the two species isolated from Hydrastis
      rhizosphere. The findings suggest that the Hydrastis root extract influences
      macroconidia germination, but that only the combined alkaloids--berberine,
      canadine, and hydrastine--appear to synergistically stimulate production of the
      mycotoxin zearalenone in the Fusarium oxysporum isolate. The Hydrastis root
      rhizosphere effect provided a selective advantage to the Fusarium isolates
      closely associated with the root tissue in comparison with the Fusarium isolate
      that had never been exposed to Hydrastis.

PMID- 17549566
TI  - Breast papillomas in the era of percutaneous needle biopsy.
AB  - BACKGROUND: The significance of breast papillomas detected on core needle biopsy
      (CNB) remains unclear. While those associated with malignancy or atypia are
      excised, no clear solution exists for benign papillomas. We sought to determine
      the indication for surgical excision, incidence of malignancy, significance, and
      natural history. METHODS: In this retrospective review, patients were divided
      into benign, atypical, or malignant cohorts based on initial results. While
      patients with malignant or atypical features were encouraged to undergo surgical
      excision, no standard recommendation was given for benign papillomas.
      Mammographic features, method of initial diagnosis, pathology results, and follow
      up data were analyzed. RESULTS: Between January 1994 to December 2005, 5,257 CNBs
      were performed at our tertiary level medical center. 206 patients were diagnosed
      with 215 breast papillomas. 174 (81%) papillomas were benign, 26 (12%) were
      associated with atypia, and 15 (7%) were associated with malignancy. Two benign
      papillomas (1.1%) developed into cancer over an average of 53 months. Average
      follow-up of those patients not undergoing excision for benign papilloma was 41
      months; we had 92 patients with greater than two year follow-up and 57 patients
      with greater than four year follow-up. Of patients with atypia or malignancy
      associated with papilloma, there was a 26% and 87% associated rate of malignancy,
      respectively. CONCLUSIONS: Benign breast papillomas diagnosed by CNB have a low
      risk of malignancy and do not need excision. However, they should be considered
      high risk lesions which require serial radiographic monitoring. Papillomas
      associated with atypia or malignancy should continue to be excised.

PMID- 17549567
TI  - Prognostic implications of netrin-1 expression and its receptors in patients with
      adenocarcinoma of the pancreas.
AB  - BACKGROUND: To assess the interaction between the expression of netrin-1 or of
      its receptors to the prognosis of ductal adenocarcinoma of the pancreas. METHODS:
      In 82 patients with resectable pancreatic adenocarcinoma who underwent curative
      operation, the expression patterns of netrin-1, deleted in colorectal carcinomas
      (DCC), UNC5H3, and neogenin were determined by immunohistochemical staining.
      Kaplan-Meier analysis was performed to assess the prognostic relevance of the
      examined expression patterns. RESULTS: Median follow-up was 15 +/- 19.9 months
      (range, 4-108 months). Patients suffering from tumors with no or little
      expression of netrin-1 (n = 67) had a median recurrence-free survival of 10
      months (95% CI, 7-13 months), while a middle to strong expression (n = 15) was
      associated with a significantly worse median recurrence-free survival of only
      four months (95% CI, three to five months, p = 0.0165). Overall and recurrence
      free survival showed no significant differences between the different expression
      patterns of DCC, UNC5H3 or neogenin. Netrin-1 expression had significant impact
      (p = 0.001) on overall survival of patients suffering from poorly differentiated
      tumors. Stratification according to the nodal status revealed significant
      influence (p = 0.007) of UNC5H3 expression on the overall survival of patients
      with pN1 status. CONCLUSION: Expression of netrin-1 has significant impact on
      time to tumor relapse in adenocarcinoma of the pancreas. Netrin-1 expression is
      associated with worse outcome in poorly differentiated pancreatic
      adenocarcinomas. Risk-stratification according to the UNC5H3 receptor expression
      pattern shows that node positive patients (pN1) with no to little UNC5H3
      expression carry a significantly worse prognosis than those with middle to strong
      UNC5H3 expression.

PMID- 17549568
TI  - Correlation of levels and patterns of genomic instability with histological
      grading of DCIS.
AB  - BACKGROUND: Histological grading of ductal carcinoma-in-situ (DCIS) lesions
      separates DCIS into three subgroups (well-, moderately, or poorly
      differentiated). It is unclear, however, whether breast disease progresses along
      a histological continuum or whether each grade represents a separate disease. In
      this study, levels and patterns of allelic imbalance (AI) were examined in DCIS
      lesions to develop molecular models that can distinguish pathological
      classifications of DCIS. METHODS: Laser microdissected DNA samples were collected
      from DCIS lesions characterized by a single pathologist including well- (n = 18),
      moderately (n = 35), and poorly differentiated (n = 47) lesions. A panel of 52
      microsatellite markers representing 26 chromosomal regions commonly altered in
      breast cancer was used to assess patterns of AI. RESULTS: The overall frequency
      of AI increased significantly (P < .001) with increasing grade (well
      differentiated, 12%; moderately differentiated, 17%; poorly differentiated, 26%).
      Levels of AI were not significantly different between well- and moderately
      differentiated grades of disease but were significantly higher (P < .0001) in
      poorly differentiated compared with well- or moderately differentiated disease.
      No statistically significant differences in patterns of AI were detected between
      well- and moderately differentiated disease; however, AI occurred significantly
      more frequently (P < .05) in high-grade lesions at chromosomes 6q25-q27, 8q24,
      9p21, 13q14, and 17p13.1, and significantly more frequently in low-grade lesions
      at chromosome 16q22.3-q24.3. CONCLUSIONS: The inability to discriminate DCIS at
      the genetic level suggests that grades 1 and 2 DCIS may represent a single, non
      high-grade form of DCIS, whereas poorly differentiated DCIS seems to be a
      genetically more advanced disease that may represent a discrete disease entity,
      characterized by a unique spectrum of genetic alterations.

PMID- 17549569
TI  - Size of sentinel node tumor deposits and extent of axillary lymph node
      involvement: which breast cancer patients may benefit from less aggressive
      axillary dissections?
AB  - BACKGROUND: In most breast cancer series, nearly 30% to 40% of all patients are
      sentinel node positive; however, in a large proportion of these, the disease is
      limited to three or fewer positive nodes. On the basis of these observations, the
      object of this study is to identify a subset of patients who might benefit from a
      less aggressive axillary dissection, without compromising staging or local
      disease control. We reviewed known clinicopathologic variables associated with a
      higher risk for axillary metastasis in 467 patients who underwent sentinel node
      mapping at our institution. We then compared the incidence of these variables in
      patients with N1a versus N2-3 stage disease. RESULTS: Although the presence of
      lymphvascular invasion in the primary tumor and extracapsular extension of tumor
      in the sentinel node were statistically significantly different between N1a and
      N2-3 patients (P < .025 and P < .01, respectively), the variable that most
      reliably separated N1a from N2-3 patients was the size of the tumor deposits in
      the sentinel node (P < .001). All patients with sentinel node tumor deposits
      <or=5 mm had three or fewer positive nodes; 95% were sentinel node-positive only,
      and 91% had single-node involvement. CONCLUSIONS: Patients at low risk for
      extensive axillary nonsentinel node involvement may benefit from a more
      conservative surgical approach to their axillae, perhaps limited to sentinel node
      biopsy only or to axillary procedures restricted to the group of axillary nodes
      in close proximity to those designated as sentinel nodes.

PMID- 17549570
TI  - Blue dye injection in the arm in order to conserve the lymphatic drainage of the
      arm in breast cancer patients requiring an axillary dissection.
AB  - BACKGROUND: Despite the widespread use of the sentinel lymph node biopsy
      technique, many patients with invasive breast cancer still undergo an axillary
      lymph node dissection and are at risk of arm lymphedema. With the new awareness
      of lymphatic spread in the axillary nodes, it should be possible to define a new
      surgical approach between sentinel lymph node biopsy and complete axillary
      dissection, a procedure preserving specifically lymph nodes in relation to the
      arm. METHODS: Twenty-one patients with an operable breast cancer requiring an
      axillary dissection underwent surgery with an attempt to separate nodes related
      to the breast from specific nodes related to the arm. After an injection of blue
      dye in the arm, the surgeon performed the axillary dissection trying to identify
      blue nodes and ducts in order to preserve lymphatic arm drainage (LAD). If the
      blue nodes were located in the normal axillary dissection, they were removed
      separately. RESULTS: In 15 of 21 patients (71%), blue nodes in relation with LAD
      were identified. In 10 (47%) patients, it was possible to dissect the LAD with
      the preservation lymphatic ducts. In 10 patients, the LAD nodes were removed:
      none of them contained metastases, despite the fact that the non-LAD axillary
      nodes contained metastases in 7 of 10 cases. CONCLUSIONS: Identifying the LAD
      with blue dye injection in the arm is possible. A subsequent study can now begin
      to determine if this procedure is safe for patients and able to prevent
      lymphedema of the arm.

PMID- 17549571
TI  - pN3M0 gastric cancer: the category that allows the sub-classification of stage-IV
      gastric cancer (IVa and IVb).
AB  - BACKGROUND: Since the publication of the fifth edition of the UICC TNM
      classification, the rate of curative surgical resection for stage-IV gastric
      cancer has increased. It is related to the N3 category, which was the prior pN1
      or pN2 in the fourth UICC TNM staging system and now pN3 in the fifth. We
      performed a retrospective analysis to determine whether the prognosis of N3M0
      gastric cancer is different from that of other stage-IV gastric cancer; this may
      support sub-division of this disease. METHODS: We analyzed 422 patients with
      stage-IV gastric cancer who underwent gastric resection from 1983 to 2002 at
      Korea University Hospital. Clinical and pathological characteristics as well as
      survival of the patients were evaluated retrospectively according to the TNM
      categories. RESULTS: The 5-year survival rate for those with N3M0 gastric cancer
      was 10.5%; this was influenced by depth of invasion (P = 0.001). According to the
      survival analysis in patients with stage-IV subtypes, the mean survival time was
      25.6 months for T1-3N3M0, 24.7 months for T4N1-2M0, 10.0 months for T4N3M0, and
      13.6 months for anyT anyNM1. Thus, the survival of patients with T4N3M0 and M1
      stage disease was significantly shorter than that of patients with T1-3N3M0 and
      T4N1-2M0 stage disease (P = 0.000). CONCLUSIONS: Sub-classification of stage-IV
      gastric cancer into IVa (T1-3N3M0, T4N1-2M0) and IVb (T4N3M0, anyT anyNM1) may be
      helpful to predict the outcome of patients with stage-IV gastric cancer.

PMID- 17549572
TI  - Surgical management and outcome in primary adenocarcinoma of the small bowel.
AB  - BACKGROUND: Primary adenocarcinoma of the small bowel is a rare malignancy and is
      associated with poor survival outcome. Patient, tumor and treatment-related
      factors were analyzed for their association with recurrence and survival.
      METHODS: Between 1971 and 2005, 64 patients with primary adenocarcinoma of the
      small bowel were treated at our institution. Clinico-pathologic data, operative
      details, postoperative treatment, recurrence pattern and survival were reviewed.
      RESULTS: The most common clinical features at presentation included abdominal
      pain (n = 33; 51.6%) or bowel obstruction (n = 20; 31.3%). The most frequently
      involved portion of the small bowel was the duodenum (n = 41; 64%). A segmental
      bowel resection was performed in 30 patients and pancreaticoduodenectomy in 14
      patients. Postoperative mortality and morbidity rates were 3.6% (n = 2) and 14.5%
      (n = 8), respectively. Of the 55 patients who underwent operative intervention, a
      curative resection was performed in 30 (54.5%). The most common sites of
      recurrence following a curative resection were the liver and lung. Median
      survival for all 64 patients was 18 months with a 5-year survival of 21.1%. On
      multivariate analysis, absence of distant metastatic disease (5-year survival
      30.4%), curative resection (5-year survival 44.8%) and pathological T stage 1-3
      (5-year survival 39.2%) were identified as independent predictors of survival.
      CONCLUSIONS: A curative resection in the absence of both distant metastases and
      pathological T4 tumor provides the best survival outcome. Recurrence at distant
      sites is the predominant pattern of failure following a curative resection,
      suggesting a role for adjuvant therapy.

PMID- 17549573
TI  - Single nucleotide polymorphisms in the promoter region of the E-cadherin gene in
      gastric cancer: case-control study in a young Mexican population.
AB  - BACKGROUND: Gastric cancer has a tendency to present at early age in the Mexican
      population, and it is frequently associated with a family history. A polymorphism
      at position -160 at the CDH1 promoter region has been reported to lead to
      transcriptional downregulation of the gene in vitro, with possible increase in
      the risk of gastric cancer. We evaluated the role of the -160A allele in the risk
      of gastric cancer in a young Mexican population. METHODS: Peripheral blood sample
      of Mexican patients younger than 45 years old with diagnosis of diffuse gastric
      cancer were obtained. We performed DNA extraction and analyzed the frequencies of
      -160 promoter polymorphism of E-cadherin gene by polymerase chain reaction-single
      strand conformational polymorphism. These frequencies were compared with those of
      healthy controls. The chi2 test for association was used to test differences of
      the genotype frequencies between normal controls and patients with gastric
      cancer. Findings were considered significant at P < .05. RESULTS: The frequency
      of the -160 A allele was significantly higher (P = .002) in 39 patients with
      diffuse gastric cancer compared with 78 matched controls. The odds ratio
      associated with the A-allele was 1.98 for C/A heterozygotes (95% CI 1.01-3.98)
      and 6.5 for A/A homozygotes (95% CI 2.1-19.6). We found an increased risk of
      diffuse gastric cancer according to family history, independent of the expression
      of the polymorphism. CONCLUSIONS: The -160 C/A polymorphism of the E-cadherin has
      a direct effect on the risk of diffuse gastric cancer at young age in Mexican
      population.

PMID- 17549574
TI  - Appointment-keeping behavior is not related to medication adherence in
      hypertensive African Americans.
AB  - OBJECTIVE: The relationship between appointment-keeping behavior, medication
      adherence (ADH), and systolic and diastolic blood pressure (SBP and DBP) was
      assessed in 153 hypertensive African Americans followed in a community-based
      practice. METHODS: ADH was assessed with a self-report questionnaire. BP was
      obtained from electronic medical records and appointment attendance was
      determined from the log of all appointments made during the 12-month study
      period. Nonadherence rates were compared across appointment attendance categories
      with chi-square. Logistic regression was used to assess the relationship between
      ADH and appointment attendance, whereas multivariate analysis of covariance
      (MANCOVA) was used to examine the relationship between appointment attendance and
      BP. RESULTS: Twenty-five percent of patients (87% women, mean age 52 years) did
      not miss any appointments, 44% missed 1-30%, and 31% missed greater than 30%.
      Adjusted nonadherence rates were similar for all 3 categories (70%, 66%, and 65%,
      respectively, p = 0.88) as were adjusted mean SBP and DBP in the MANCOVA model,
      [F (4, 218) = 1.13, p = .34]. Logistic regression analysis did not indicate a
      significant relationship between appointment attendance and ADH. CONCLUSIONS:
      Appointment-keeping behavior was not related to ADH or BP among hypertensive
      African Americans. It should not be used as a proxy for ADH in this patient
      population.

PMID- 17549576
TI  - Are physicians discussing prostate cancer screening with their patients and why
      or why not? A pilot study.
AB  - BACKGROUND: Prostate cancer screening (PCS) is controversial. Ideally, patients
      should understand the risks and benefits of screening before undergoing PSA
      testing. This study assessed whether primary care physicians routinely discuss
      PCS and explored the barriers to and facilitators of these discussions. METHODS:
      Qualitative pilot study involving in-depth, semistructured interviews with 18
      purposively sampled, academic and community-based primary care physicians.
      Barriers and facilitators of PCS discussions were ascertained using both
      interviews and chart-stimulated recall--a technique utilizing patient charts to
      probe recall and provide context to physician decision-making during clinic
      encounters. Analysis was performed using consensus conferences based on grounded
      theory techniques. RESULTS: All 18 participating physicians reported that they
      generally discussed PCS with patients, though 6 reported sometimes ordering PSA
      tests without discussion. A PCS discussion occurred in only 16 (36%) of the 44
      patient-physician encounters when patients were due for PCS that also met
      criteria for chart-stimulated recall. Barriers to PCS discussion were patient
      comorbidity, limited education/health literacy, prior refusal of care, physician
      forgetfulness, acute-care visits, and lack of time. Facilitators of PCS
      discussion included patient-requested screening, highly educated patients, family
      history of prostate cancer, African-American race, visits for routine physicals,
      review of previous PSA results, extra time during encounters, and reminder
      systems. CONCLUSIONS: PCS discussions sometimes do not occur. Important barriers
      to discussion are inadequate time for health maintenance, physician
      forgetfulness, and patient characteristics. Future research should explore using
      educational and decision support interventions to involve more patients in PCS
      decisions.

PMID- 17549577
TI  - Bioidentical hormones for menopausal hormone therapy: variation on a theme.
AB  - BACKGROUND: Progesterone creams and natural or bioidentical compounded estrogen
      preparations are being promoted to consumers as safe alternatives to conventional
      menopausal hormone therapy and as health-promoting tonics. No reliable data
      support these claims. SAFETY: Natural hormones, including estradiol, estriol,
      estrone, and progesterone, can be expected to have the same adverse event profile
      as conventional menopausal hormone regimens. SALIVARY HORMONE TESTS: Salivary
      tests may be used to persuade asymptomatic consumers to use hormones (or
      symptomatic patients to use higher doses than those needed to mitigate symptoms),
      a practice that can be expected to result in adverse events.

PMID- 17549578
TI  - Glutamate-induced calcium transients in rat neurons of the dorsal motor nucleus
      of the vagus.
AB  - The dorsal motor nucleus of the vagus (DMNV) integrates peripheral and central
      signals and sends efferent output to the gastrointestinal system. Glutamate, the
      major excitatory neurotransmitter of the central nervous system, causes increases
      in intracellular calcium in DMNV neurons. The mechanisms by which glutamate
      activates calcium signaling in the DMNV were examined. DMNV neurons were isolated
      from neonatal rat brainstem using microdissection and enzymatic digestion.
      Exposure to glutamate caused intracellular Ca(2+) increments in greater than 80%
      of cells. Removal of extracellular Ca(2+) abolished intracellular Ca(2+)
      transients. Kynurenic acid, a nonspecific glutamate receptor antagonist,
      abolished intracellular Ca(2+) transients. Exposure to glutamate while blocking
      AMPA receptors with GYKI 52466 abolished the Ca(2+) response. Exposure to
      (S)AMPA, an AMPA receptor agonist, caused intracellular Ca(2+) increments in 97%
      of cells. Activation and antagonism of NMDA and kainate receptors produced no
      changes compared to control experiments. NiCl, a nonspecific Ca(2+) channel
      blocker, abolished intracellular Ca(2+) transients. Blocking T-type Ca(2+)
      channels with mibefradil abolished the Ca(2+) response in 76% of cells. Blockade
      of L-type and N-type Ca(2+) channels did not affect the Ca(2+) response.
      Glutamate mediates intracellular Ca(2+) currents in DMNV neurons via the AMPA
      receptor and T-type Ca(2+) channels, allowing influx of extracellular Ca(2+).

PMID- 17549579
TI  - Homocysteine and fracture risk in postmenopausal women: the OFELY study.
AB  - Homocysteine has recently been described as an independent risk factor for
      osteoporotic fractures in the elderly. We prospectively followed 671
      postmenopausal women belonging to the OFELY study, mean age 62 years, during a
      mean follow-up of 10 years. After adjustment for age, there was no significant
      relation between the plasma level of homocysteine and the subsequent risk of
      fracture. INTRODUCTION: Plasma homocysteine increases with age. Recent studies
      have described homocysteine as an independent risk factor for osteoporotic
      fractures in elderly. We investigated the role of plasma homocysteine in the
      subsequent risk of fractures in healthy ambulatory postmenopausal women. METHODS:
      Homocysteine was measured at baseline in 671 postmenopausal women from the OFELY
      cohort (mean age 62.2 +/- 9 years). Incident clinical fractures were recorded
      during annual follow-up and vertebral fractures were evaluated with radiographs
      every four years. A cox proportional hazards model based on time to first
      fracture was used to calculate hazard ratios for quartiles of homocysteine
      values. RESULTS: Mean homocysteine was 10.6 +/- 3.4 mumol/l, increasing with age.
      After adjustment for age, homocysteine was significantly associated with physical
      activity, calcium intake, serum albumin and serum creatinine but not with bone
      turnover markers and bone mineral density. During a mean follow-up of 10 years,
      183 fractures occurred among 134 women. After adjustment for age, the overall
      relative risk of fracture for each 1 SD increment of homocysteine was 1.03 (95%CI
      0.87-1.31). Fracture risk was higher in women with homocysteine in the highest
      quartile without adjustment but no longer after adjustment for age. CONCLUSIONS:
      Homocysteine is not an independent risk factor of osteoporotic fractures in
      healthy postmenopausal women from the OFELY cohort with a broad age range.

PMID- 17549580
TI  - Treatment with infliximab may contribute to the development of peripheral
      neuropathy among the patients with rheumatoid arthritis.

PMID- 17549581
TI  - Osseous mastocytosis of the knee.
AB  - Mastocytosis is a rare pathology with possible bone involvement. This report
      describes an unusual case of solitary osteolytic lesion of the proximal right
      tibia, revealing an osseous mastocytosis, treated by bone cement injection.
      Follow-up showed a good clinical and radiological outcome, and the patient
      remains symptom-free 9 months after her surgery. To our knowledge, this is the
      first case reported in the literature.

PMID- 17549582
TI  - Pneumatization of the optic nerve sheaths.

PMID- 17549583
TI  - Understanding hERG inhibition with QSAR models based on a one-dimensional
      molecular representation.
AB  - Blockage of the potassium channel encoded by the human ether-a-go-go related gene
      (hERG) is well understood to be the root cause of the cardio-toxicity of numerous
      approved and investigational drugs. As such, a cascade of in vitro and in vivo
      assays have been developed to filter compounds with hERG inhibitory activity.
      Quantitative structure activity relationship (QSAR) models are used at the very
      earliest part of this cascade to eliminate compounds that are likely to have this
      undesirable activity prior to synthesis. Here a new QSAR technique based on the
      one-dimensional representation is described in the context of the development of
      a model to predict hERG inhibition. The model is shown to perform close to the
      limits of the quality of the data used for model building. In order to make
      optimal use of the available data, a general robust mathematical scheme was
      developed and is described to simultaneously incorporate quantitative data, such
      as IC50 = 50 nM, and qualitative data, such as inactive or IC50 > 30 microM into
      QSAR models without discarding any experimental information.

PMID- 17549584
TI  - Overview of the phylogenetic relationships of some southern Brazilian species
      from section Torva and related sections of "spiny Solanum" (Solanum subgenus
      Leptostemonum, Solanaceae).
AB  - One of the major concerns of conservation biology is the knowledge on
      biodiversity. Many taxa have not yet been described and plant taxonomists are
      working hard to change this situation. This work presents a taxonomic overview of
      Solanum section Torva, from South Brazil, which still poorly understood. The
      section includes species known as "jurubeba" which are of considerable interest
      because of their pharmacological properties. Despite their higher economic value,
      it is difficult to identify the "jurubebas" correctly due to their taxonomic
      problems. A few questions on evolution concerning phylogenetic relationships in
      this section and other related sections of subgenus Leptostemonum were
      investigated to clarify the species circumscription and taxonomic issues. Eighty
      samples were analysed based on sequence variability of the internal transcribed
      spacers (ITS) of the nuclear ribosomal DNA, as well as the chloroplast intron
      trnL, trnL-trnF and trnS-trnG spacers. Five different matrixes were analyzed as
      the basis for a phylogenetic approach. The combined data from the chloroplast
      analyses formed well-supported trees. Solanum section Torva was proposed as a
      monophyletic group and it is close to S. melongena, S. jamaicense and S.
      sisymbriifolium.

PMID- 17549585
TI  - Effects of extending the light phase on diapause induction in a Japanese
      population of the two-spotted spider mite, Tetranychus urticae.
AB  - Artificial lighting is a merit of a 'plant factory', which might be utilized to
      suppress an increase in pest population. We investigated the effects of extending
      the light phase on diapause induction in the two-spotted spider mite (TSSM),
      Tetranychus urticae. TSSM were reared at 18 degrees C under light phases ranging
      from 2 to 64 h combined with a constant dark phase of 16 h in aluminum bottles,
      with white light emitting diodes attached inside to minimize fluctuations in air
      temperature between the light and dark phases. Diapause was induced in adult TSSM
      females when the light phase was 24 h or shorter, and diapause induction was
      inhibited when the light phase extended over 32 h. The development of deutonymphs
      was delayed under a diapause-inducing photoperiod. Diapause inducing photoperiods
      may suppress an increase in the TSSM population, by slowing down development and
      reproduction.

PMID- 17549586
TI  - Management of Tetranychus urticae (Acari: Tetranychidae) in strawberry fields
      with Neoseiulus californicus (Acari: Phytoseiidae) and acaricides.
AB  - The purpose of this study was to evaluate the performance of Neoseiulus
      californicus (McGregor) for the control of Tetranychus urticae Koch in commercial
      strawberry fields, under greenhouse conditions, in association or not with the
      use of acaricides. The N. californicus strain used in this study was tolerant or
      resistant to several pesticides. Three experiments were carried out in the State
      of Sao Paulo, Brazil. For the first experiment, the initial infestation of T.
      urticae was 87.1 active stages per leaflet. Two applications of propargite were
      made on the first and the 14th day of the experiment. Approximately 2 h after
      each propargite application, N. californicus was released at a rate of 3.0 and
      1.9 adult mites per plant, respectively, for each application. The population of
      T. urticae decreased from 87.1 to 2.8 mites per leaflet in the first three weeks.
      After this period, the population of T. urticae was maintained at low levels
      (<or=1.5 mites/leaflet) until the end of the experiment (10th week). Propargite
      and dimethoate sprayed on the strawberry field did not affect significantly the
      population of this predaceous mite. For the second experiment, the infestation of
      T. urticae was 29.1 mites per leaflet, when the acaricide chorfenapyr was applied
      on the strawberry field. The release of N. californicus (2 mites per plant) was
      made 2 weeks after spraying the acaricide. The population of T. urticae was
      maintained at low levels (<or=2.8 mites/leaflet) for 8 weeks (evaluation period).
      The T. urticae infestations in plots with N. californicus were significantly
      lower than in non-release plots, for the experiments 1 and 2. In the third
      experiment, the initial infestation of T. urticae was 40.5 mites per leaflet
      (55.5 active stages/leaflet on release plants; 25.5 active stages/leaflet on non
      release plants). Three releases of N. californicus (average rate of 3.0 adult
      mites/plant), without any acaricide application, were not sufficient to reduce
      significantly the T. urticae population in release plots (release plants + non
      release plants) in 6 weeks from the first release, however, the spider mite
      population decreased from 55.5 to 7.8 active stages per leaflet on release
      plants, during this period. Interplant dispersal of N. californicus was low in
      this strawberry field with high infestation of T. urticae. The studies indicate
      the viability of the use of this strain of N. californicus for the control of T.
      urticae in strawberry fields under greenhouse conditions, especially in
      association with selective acaricides.

PMID- 17549587
TI  - Effect of ectoparasitic Pimeliaphilus plumifer mites (Acari: Pterygosomatidae) on
      Meccus pallidipennis (Hemiptera: Reduviidae) and several other Chagas' disease
      vectors under laboratory conditions.
AB  - Several biological parameters were evaluated to determine the capacity of
      Pimeliaphilus plumifer as biological control agent of Triatominae bugs. When P.
      plumifer and bugs of a variety of triatomine species were forced together in
      cages in the laboratory, the incidence of mite infestation was the following:
      Meccus pallidipennis > M. bassolsae > Triatoma rubida > M. longipennis > M.
      picturatus, and practically no mites were found on T. infestans and Rhodnius
      prolixus. Adults and hexapod larvae of P. plumifer were the only stages found to
      parasitize on M. pallidipennis. Fourth and fifth instar nymphs of this bug
      appeared most susceptible to mite infestation. P. plumifer mites located
      preferably on the coxae, ventral abdomen and pronotum of M. pallidipennis bugs.
      The number of blood meals, amount of ingested blood, and resistance to starvation
      of M. pallidipennis were similar in both the control and the mite infested
      groups. On the other hand, mite infection reduced molting rate in nymphs and
      longevity in adults, increased mortality in third-fifth instar nymphs, and fewer
      viable eggs were laid by females infected with P. plumifer. These effects could
      be related with nutritional deficiencies. Our results support the use of P.
      plumifer mites as control agents of host Triatominae species.

PMID- 17549588
TI  - Experimental method for isolating and identifying dust mites from sputum in
      pulmonary acariasis.
AB  - The aim of this study was to pilot a simpler and more effective method for
      identifying dust mites in sputum. Dust mites and their allergens have been
      implicated in respiratory diseases, including pulmonary acariasis, and several
      studies have identified mites in sputum. Further research is dependent on the
      development of a faster and simpler diagnostic test. We have demonstrated that
      dust mites artificially introduced into sputa, could be identified after the
      sputa were liquefied with bleach, when the liquid sample was observed under the
      microscope. Liquefaction times for serous, mucous, purulent and hemoptoic sputa
      varied from 10 to 30 min (mean 17.5). The test had a sensitivity of 80% (95% CI
      68.2-88.2%) as 46/60 mites were identified. This procedure can be performed
      quickly at room temperature, is simple, inexpensive, repeatable, and less
      labourious than previous methods.

PMID- 17549589
TI  - Effects of intermittent parathyroid hormone (PTH) administration on SOST mRNA and
      protein in rat bone.
AB  - Sclerostin, the secreted protein product of the SOST gene, which is mainly
      expressed by osteocytes, has recently been proposed as a negative regulator of
      bone osteoblastogenesis. Chronic elevation of PTH reduces SOST expression by
      osteocytes, while controversial results have been obtained by intermittent PTH
      administration. We have investigated the effects of intermittently administered
      PTH on SOST expression and sclerostin localization, comparing them with those of
      controls, as they appeared in three different bone segments of rat tibia:
      secondary trabecular metaphyseal and epiphyseal bone, and cortical diaphyseal
      bone. The histomorphometric results demonstrate that PTH enhances bone turnover
      through anabolic effects, as shown by the association of increased bone
      resorption variables with a significant rise in BV/TV, Tb.Th and Tb.N and a fall
      in Tb.Sp. PTH induces a SOST mRNA and protein fall in secondary metaphyseal
      trabeculae, diaphyseal bone and in epiphyseal trabeculae. Numbers of sclerostin
      immunopositive osteocytes/mm(2) show no change, compared with controls; there are
      fewer sclerostin-positive osteocytes in secondary metaphyseal trabeculae than in
      the other two bone areas, both in the control and PTH groups. The low numbers of
      sclerostin-positive osteocytes in the metaphyseal trabecular bone seem to be
      directly related to the fact that this area displays a high remodeling rate. The
      anabolic effects of PTH are in line with the fall of SOST mRNA and protein in all
      the three bone segments examined; the rise of bone turnover supports a negative
      role of SOST in bone formation.

PMID- 17549590
TI  - Development of an in vitro assay for the investigation of metabolism-induced drug
      hepatotoxicity.
AB  - In a number of adverse drug reactions leading to hepatotoxicity drug metabolism
      is thought to be involved by generation of reactive metabolites from nontoxic
      drugs. In this study, an in vitro assay was developed for measurement of the
      impact of metabolic activation of compound on the cytotoxicity toward a human
      hepatic cell line. HepG2 cells were treated for 6 h with compound in the presence
      or absence of rat liver S9-mix, and the viability was measured using the MTT
      test. The cytotoxicity of cyclophosphamide was substantially increased by S9-mix
      in the presence of NADPH. Three NADPH sources were tested: NADPH (1 mmol/L) or
      NADPH regenerating system with either NADP(+)/glucose 6-phosphate (G6P) or
      NADP(+)/isocitrate. All three NADPH sources increased the cytotoxicity of
      cyclophosphamide to a similar extent. Eight test compounds known to cause
      hepatotoxicity were tested. For these, only the cytotoxicity of diclofenac was
      increased by S9 enzymes when an NADPH regenerating system was used. The increased
      toxicity was NADPH dependent. Reactive drug metabolites of diclofenac, formed by
      NADPH-dependent metabolism, were identified by LC-MS. Furthermore, an increase in
      toxicity, not related to enzymatic activity but to G6P, was observed for
      diclofenac and minocycline. Tacrine and amodiaquine displayed decreased toxicity
      with S9-mix, and carbamazepine, phenytoin, bromfenac and troglitazone were
      nontoxic at all tested concentrations, with or without S9-mix. The results show
      that this method, with measurement of the cytotoxicity of a compound in the
      presence of an extracellular metabolizing system, may be useful in the study of
      cytotoxicity of drug metabolites.

PMID- 17549591
TI  - The flavonoid rutin induces astrocyte and microglia activation and regulates TNF
      alpha and NO release in primary glial cell cultures.
AB  - Astrocyte and microglia cells play an important role in the central nervous
      system (CNS). They react to various external aggressions by becoming reactive and
      releasing neurotrophic and/or neurotoxic factors. Rutin is a flavonoid found in
      many plants and has been shown to have some biological activities, but its direct
      effects on cells of the CNS have not been well studied. To investigate its
      potential effects on CNS glial cells, we used both astrocyte primary cultures and
      astrocyte/microglia mixed primary cell cultures derived from newborn rat cortical
      brain. The cultures were treated for 24 h with rutin (50 or 100 micromol/L) or
      vehicle (0.5% dimethyl sulfoxide). Mitochondrial function on glial cells was not
      evidenced by the MTT test. However, an increased lactate dehydrogenase activity
      was detected in the culture medium of both culture systems when treated with 100
      micromol/L rutin, suggesting loss of cell membrane integrity. Astrocytes exposed
      to 50 micromol/L rutin became reactive as revealed by glial fibrillary acidic
      protein (GFAP) overexpression and showed a star-like phenotype revealed by
      Rosenfeld's staining. The number of activated microglia expressing OX-42
      increased in the presence of rutin. A significant increase of nitric oxide (NO)
      was observed only in mixed cultures exposed to 100 micromol/L rutin. Enhanced
      TNFalpha release was observed in astrocyte primary cultures treated with 100
      micromol/L rutin and in mixed primary cultures treated with 50 and 100
      micromol/L, suggesting different sensitivity of both activated cell types. These
      results demonstrated that rutin affects astrocytes and microglial cells in
      culture and has the capacity to induce NO and TNFalpha production in these cells.
      Hence, the impact of these effects on neurons in vitro and in vivo needs to be
      studied.

PMID- 17549592
TI  - Youth smokers' beliefs about different cessation approaches: are we providing
      cessation interventions they never intend to use?
AB  - INTRODUCTION: Most youth smokers intend to quit, but the majority is neither
      aware nor interested in most conventional cessation approaches. As such, a
      critical first step in understanding youth cessation is to better understand the
      beliefs youth have about different cessation options. METHODS: This cross
      sectional study used self-reported data collected from 26,379 grade 9 to 12
      students in Ontario, Canada. We examined both the attitudes of youth smokers
      toward common smoking cessation approaches and factors associated with intentions
      to join a school-based cessation program. RESULTS: The majority of youth smokers
      intend to quit smoking but tend to have negative attitudes toward most formal
      smoking cessation approaches; Nicotine Replacement Therapy (NRT) was an
      exception. Among occasional smokers, self-identification as a smoker and being
      physically active were positively associated with intending to join a school
      based cessation program. Having tried to quit smoking at least once in the past
      year more than doubled the likelihood of being interested in a school-based
      program among both occasional and daily smokers. CONCLUSION: Findings have the
      potential for informing the development of more effective campaigns for engaging
      adolescent smokers into smoking cessation treatment. Results also reinforce the
      need for programmatic innovation within and beyond school settings.

PMID- 17549593
TI  - Vitamin D intake and breast cancer risk in postmenopausal women: the Iowa Women's
      Health Study.
AB  - Vitamin D, a prosteroid hormone with anti-proliferative and pro-differentiation
      activity, is thought to act as a cancer chemopreventive agent. This study
      evaluated the association between vitamin D intake and breast cancer risk among
      women in a large prospective cohort study. A total of 34,321 postmenopausal women
      who had completed a questionnaire that included diet and supplement use were
      followed for breast cancer incidence from 1986 to 2004. Adjusted relative risks
      (RR) for breast cancer were calculated for dietary, supplemental, and total
      vitamin D intake among all women. The adjusted RR of breast cancer for women
      consuming >800 IU/day versus <400 IU/day total vitamin D was 0.89 (95% CI: 0.77
      1.03). RRs were stronger among women with negative than positive ER or PR status.
      The association of high vitamin D intake with breast cancer was strongest in the
      first 5 years after baseline dietary assessment (RR = 0.66; 95% CI: 0.46-0.94
      compared with lowest-intake group), and diminished over time. Changes in vitamin
      D intake over time might have contributed to the diminished association observed
      in later years. Vitamin D intake of >800 IU/day appears to be associated with a
      small decrease in risk of breast cancer among postmenopausal women. Studies
      evaluating all sources of vitamin D, especially sun exposure, are needed to fully
      understand the association between vitamin D and breast cancer risk.

PMID- 17549594
TI  - Physical activity and inactivity in relation to sex hormone, prolactin, and
      insulin-like growth factor concentrations in premenopausal women - exercise and
      premenopausal hormones.
AB  - An association between physical activity and premenopausal breast cancer risk may
      be due, in part, to relationships with sex hormones or growth factors. Therefore,
      we assessed whether MET-h/week of total physical activity (moderate-to-vigorous
      intensity), walking, or vigorous physical activity, and h/week of standing or
      sitting were associated with plasma concentrations of several hormones. We
      examined levels of estrogens, androgens, progesterone, prolactin, sex hormone
      binding globulin (SHBG), insulin-like growth factor-1 (IGF-1), IGF binding
      protein-3, and growth hormone (GH) in 565 premenopausal women, ages 33-52 years,
      from the Nurses' Health Study II (NHSII). About 87% of women had both timed
      follicular and luteal samples; other women had one untimed sample. In general we
      observed few associations between sex hormone or IGF levels and measures of
      physical activity or inactivity. However, free testosterone was modestly
      inversely associated with total physical activity (p-trend = 0.02). Luteal
      estradiol, free estradiol, and estrone also were inversely associated with total
      physical activity (p-trend = 0.10, 0.04, 0.01, respectively); however, the trend
      was substantially attenuated when excluding women with anovulatory cycles or
      irregular cycles. These cross-sectional results suggest that physical activity
      and inactivity have limited associations with premenopausal sex hormone and
      growth factor levels, except possibly luteal estrogens.

PMID- 17549596
TI  - Early learner perceptions of the attributes of effective preceptors.
AB  - Medical education in the US has adapted to the shift of patient care from
      hospital to ambulatory settings by developing educational opportunities in
      outpatient settings. Faculty development efforts must acknowledge learners'
      perspectives to be effective in improving teaching and learning. Clinics provide
      important and unique learning opportunities, but also present different
      challenges for preceptors (i.e., physician teachers) and learners. Multiple
      studies have identified characteristics of effective preceptors of ambulatory
      care medicine. However, most of these studies were conducted among residents or
      students with clinical experience. To investigate preclinical, second-year
      medical students' perceptions of preceptor quality, we conducted an exploratory
      qualitative study using analysis of student learning journals. The purposive
      sample included 120 medical students in a private, Midwestern medical school in
      the United States. Learning journals of 110 students for two semesters were
      reviewed. Five attributes of an effective preceptor emerged: (1) Demonstrates
      professional expertise (2) Actively engages students in learning (3) Creates a
      positive environment for teaching and learning (4) Demonstrates collegiality and
      professionalism (5) Discusses career-related topics and concerns. Our findings
      suggest preclinical learners often begin initial clinical experiences with
      sophisticated definitions of professional expertise, and hold specific
      expectations for professionalism. These are based on previous coursework and
      personal experience. These expectations influence their perceptions of effective
      preceptors and learning experiences. Early clinical experiences can also
      influence perceptions about career and specialty choice. Improving our
      understanding of preclinical learners' perceptions of preceptor quality will
      improve the efficacy of faculty development efforts and learning experiences.

PMID- 17549595
TI  - Exogenous hormones and colorectal cancer risk in Canada: associations stratified
      by clinically defined familial risk of cancer.
AB  - OBJECTIVE: This work assessed associations between colorectal cancer risk and
      postmenopausal/contraceptive hormones; subgroup analyses included women with a
      clinically defined family history of cancer. METHODS: A population based case
      control study of incident colorectal cancer was conducted among women aged 20-74
      years in Ontario and Newfoundland & Labrador, Canada. Incident cases (n = 1,404)
      were selected from provincial cancer registries and controls (n = 1,203) were
      identified through property records, and other means, between January 1997 and
      April 2006. Family history of cancer, exogenous hormone-use, and other risk
      factors were collected via self-administered questionnaires. Multivariate
      unconditional logistic regression analyses were used to estimate odds ratios
      (ORs) and corresponding 95% confidence intervals (CIs). RESULTS: Decreased risks
      of colorectal cancer were observed with ever-users of: hormonal contraceptives
      (OR: 0.77; CI: 0.65-0.91), estrogen-only postmenopausal hormones (OR: 0.60; CI:
      0.47-0.75), and estrogen-progestin postmenopausal hormones (OR: 0.70; CI: 0.52
      0.95). Risk estimates were similar between women with and without a strong
      familial history of cancer. Age at initiation of hormonal contraceptives was
      associated with colorectal cancer risk; women who initiated use at younger ages
      (age <22 years: OR: 0.60; CI: 0.47-0.77) experienced a greater reduced risk of
      disease than women who initiated use at later ages (age 30+: OR: 0.92; CI: 0.68
      1.24; p (trend): 0.0026). CONCLUSIONS: These results indicate that exogenous
      hormone-use is linked with reduced risk of colorectal cancer among women with a
      strong familial risk of cancer, consistent with observations on population
      samples of sporadic colorectal cancer cases. A potential age-effect for use of
      hormonal contraceptives warrants further attention.

PMID- 17549597
TI  - Synthesis of C-11 modified mifepristone analog libraries.
AB  - Substitution of the C-11 aniline of mifepristone can provide compounds with
      altered pharmacokinetic and pharmacodynamic (PK/PD) profiles that may find use
      for new indications. The development of new steroid intermediates and specialized
      library synthesis methods were required to enable the efficient preparation of
      structurally complex C-11 modified mifepristone analogs.

PMID- 17549598
TI  - Expression profiles as detailed snapshots of biological states.

PMID- 17549599
TI  - A mouse transgene drives embryonic dorsal posterior commissure expression.
AB  - In this report we generated mice co-transgenic for a minimal promoter LacZ
      construct and a mouse BAC from the gene poor region upstream of the Hoxd cluster.
      In addition to expression in the distal limb, genital bud, and spinal cord, we
      show that this BAC transgene also reproducibly drives unique bilateral, dorsal
      posterior commissure expression. The ability of this BAC to direct posterior
      commissure expression makes it worthy of further study as a valuable tool in
      transgenic/targeting experiments.

PMID- 17549600
TI  - Transgene integration and organization in cotton (Gossypium hirsutum L.) genome.
AB  - While genetically modified upland cotton (Gossypium hirsutum L.) varieties are
      ranked among the most successful genetically modified organisms (GMO), there is
      little knowledge on transgene integration in the cotton genome, partly because of
      the difficulty in obtaining large numbers of transgenic plants. In this study, we
      analyzed 139 independently derived T0 transgenic cotton plants transformed by
      Agrobacterium tumefaciens strain AGL1 carrying a binary plasmid pPZP-GFP. It was
      found by PCR that as many as 31% of the plants had integration of vector backbone
      sequences. Of the 110 plants with good genomic Southern blot results, 37% had
      integration of a single T-DNA, 24% had two T-DNA copies and 39% had three or more
      copies. Multiple copies of the T-DNA existed either as repeats in complex loci or
      unlinked loci. Our further analysis of two T1 populations showed that segregants
      with a single T-DNA and no vector sequence could be obtained from T0 plants
      having multiple T-DNA copies and vector sequence. Out of the 57 T-DNA/T-DNA
      junctions cloned from complex loci, 27 had canonical T-DNA tandem repeats, the
      rest (30) had deletions to T-DNAs or had inclusion of vector sequences.
      Overlapping micro-homology was present for most of the T-DNA/T-DNA junctions
      (38/57). Right border (RB) ends of the T-DNA were precise while most left border
      (LB) ends (64%) had truncations to internal border sequences. Sequencing of
      collinear vector integration outside LB in 33 plants gave evidence that collinear
      vector sequence was determined in agrobacterium culture. Among the 130 plants
      with characterized flanking sequences, 12% had the transgene integrated into
      coding sequences, 12% into repetitive sequences, 7% into rDNAs. Interestingly, 7%
      had the transgene integrated into chloroplast derived sequences. Nucleotide
      sequence comparison of target sites in cotton genome before and after T-DNA
      integration revealed overlapping microhomology between target sites and the T-DNA
      (8/8), deletions to cotton genome in most cases studied (7/8) and some also had
      filler sequences (3/8). This information on T-DNA integration in cotton will
      facilitate functional genomic studies and further crop improvement.

PMID- 17549602
TI  - Renal involvement in lymphoma: prevalence and various patterns of involvement on
      abdominal CT.
AB  - OBJECTIVE: The kidney is a frequent site of involvement in lymphoproliferative
      disorders. The aim of this study was to demonstrate the prevalence and spectrum
      of morphologic appearances of renal involvement in patients with lymphoma on
      helical computed tomographic (CT) scan. METHODS: Three phases of post-contrast
      helical CT of the abdomen in 74 patients with lymphoma were reviewed for possible
      renal involvement: the cortico-medullary, nephrographic and delayed excretory
      phases. Tumor characteristics, patterns of distribution and enhancement features
      were evaluated. RESULTS: Of the 74 patients with lymphoma, 11 had CT evidence of
      renal involvement--ten with non-Hodgkin's lymphoma and one with Hodgkin's
      lymphoma--representing 15% of all patients scanned for routine staging of
      histologically diagnosed lymphoma. Five types of renal involvement were observed:
      enlarged lobular non-enhancing kidneys (four patients); bilateral multiple renal
      masses (two patients); focal single non-enhancing mass (two patients); perirenal
      infiltrations from retroperitoneal extension (two patients); bilateral diffuse
      areas of non-enhancing hypo-densities (one patient). CONCLUSION: Five distinct
      patterns of renal involvement with lymphoma were detected with helical CT. The
      most common appearance was enlarged lobular kidneys. CT with intravenous contrast
      enhancement is currently the approach of choice for both the evaluation of renal
      involvement as well as for accurate staging of lymphoma. Awareness of different
      patterns of renal involvement in lymphoma allows proper differentiation from
      other similar diseases.

PMID- 17549601
TI  - Over-expression of the apple spermidine synthase gene in pear confers multiple
      abiotic stress tolerance by altering polyamine titers.
AB  - An apple spermidine synthase (SPDS) gene (MdSPDS1) was verified to encode a
      functional protein by the complementation of the spe3 yeast mutant, which lacks
      the SPDS gene. To justify our hypothesis that apple SPDS is involved in abiotic
      stress responses and to obtain transgenic fruit trees tolerant to abiotic
      stresses as well, MdSPDS1-over-expressing transgenic European pear (Pyrus
      communis L. 'Ballad') plants were created by Agrobacterium-mediated
      transformation. A total of 21 transgenic lines showing various spermidine (Spd)
      titers and MdSPDS1 expression levels were obtained. Selected lines were exposed
      to salt (150 mM NaCl), osmosis (300 mM mannitol), and heavy metal (500 microM
      CuSO4) stresses for evaluating their stress tolerances. Transgenic line no. 32,
      which was revealed to have the highest Spd accumulation and expression level of
      MdSPDS1, showed the strongest tolerance to these stresses. When growth
      increments, electrolyte leakage (EL), and values of thiobarbituric acid reactive
      substances (TBARS) were monitored, line no. 32 showed the lowest growth
      inhibition and the least increase in EL or TBARS under stress conditions. Spd
      titers in wild-type and transgenic lines showed diverse changes upon stresses,
      and these changes were not consistent with the changes in MdSPDS1 expressions.
      Moreover, there were no differences in the sodium concentration in the shoots
      between the wild type and line no. 32, whereas the copper concentration was
      higher in the wild type than in line no. 32. Although the mechanism(s) underlying
      the involvement of polyamines in stress responses is not known, these results
      suggest that the over-expression of the SPDS gene substantially increased the
      tolerance to multiple stresses by altering the polyamine titers in pear. Thus,
      MdSPDS1-over-expressing transgenic pear plants could be used to improve desert
      land and/or to repair polluted environments.

PMID- 17549604
TI  - Medical humanities and philosophy: is the universe expanding or contracting?
AB  - The question of whether the universe is expanding or contracting serves as a
      model for current questions facing the medical humanities. The medical humanities
      might aptly be described as a metamedical multiverse encompassing many separate
      universes of discourse, the most prominent of which is probably bioethics.
      Bioethics, however, is increasingly developing into a new interdisciplinary
      discipline, and threatens to engulf the other medical humanities, robbing them of
      their own distinctive contributions to metamedicine. The philosophy of medicine
      considered as a distinct field of study has suffered as a result. Indeed,
      consensus on whether the philosophy of medicine even constitutes a legitimate
      field of study is lacking. This paper presents an argument for the importance of
      a broad conception of the philosophy of medicine and the central role it should
      play in organizing and interpreting the various fields of study that make up the
      metamedical multiverse.

PMID- 17549606
TI  - Can the dead be brought into disrepute?
AB  - Queen Christina of Sweden was unconventional in her time, leading to hypotheses
      on her gender and possible hermaphroditic nature. If genetic analysis can
      substantiate the latter claim, could this bring the queen into disrepute 300
      years after her death? Joan C. Callahan has argued that if a reputation changes,
      this constitutes a change only in the group of people changing their views and
      not in the person whose reputation it is. Is this so? This paper analyses what
      constitutes change and draws out the implications to the reputation of the dead.
      It is argued that a reputation is a relational property which can go through
      changes. The change is "real" for the group changing their views on Queen
      Christina and of a Cambridge kind for the long dead queen herself. Cambridge
      changes result in new properties being acquired, some of which can be of
      significance. Although the dead cannot go through any non-relational changes, it
      is possible for the dead to change properties through Cambridge changes. In this
      sense changes in reputation do affect the dead, and thus Queen Christina can
      acquire a new property, in this case possibly a worse reputation.

PMID- 17549605
TI  - Inscriptions of violence: societal and medical neglect of child abuse--impact on
      life and health.
AB  - OBJECTIVE: A sickness history from General Practice will be unfolded with regard
      to its implicit lived meanings. This experiential matrix will be analyzed with
      regard to its medico-theoretical aspects. METHOD: The analysis is grounded in a
      phenomenology of the body. The patient Katherine Kaplan lends a particular
      portrait to the dynamics that are enacted in the interface between socially
      silenced domestic violence and the theoretical assumptions of human health as
      these inform the clinical practice of health care. RESULTS: By applying an
      understanding of sickness that transcends the mind-body split, a concealed and
      complex logic emerges. This logic is embedded in a nexus of the impact of
      childhood abuse experience and the medical disinterest in subjective experiences
      and their impact on selfhood and health. Its core is twofold: the violation of
      embodiment resulting from intra-familial abuse and existential threat, and the
      embodiment of violation resulting from social rules and the theoretically blinded
      medical gaze. CONCLUSION: A considerable medical investment, apparently conducted
      in a correct and consistent manner as to diagnostic and therapeutic measures,
      results in the complete incapacitation of a young physician.

PMID- 17549607
TI  - Macrophage inflammatory protein-1alpha (MIP-1alpha) enhances a receptor activator
      of nuclear factor kappaB ligand (RANKL) expression in mouse bone marrow stromal
      cells and osteoblasts through MAPK and PI3K/Akt pathways.
AB  - Osteolytic lesions are rapidly progressive during the terminal stages of myeloma,
      and the bone pain or bone fracture that occurs at these lesions decreases the
      patients' quality of life to a notable degree. In relation to the etiology of
      this bone destruction, it has been reported recently that MIP-1alpha, produced in
      large amounts in myeloma patients, acts indirectly on osteoclastic precursor
      cells, and activates osteoclasts by way of bone-marrow stromal cells or
      osteoblasts, although the details of this process remain obscure. In the present
      study, our group investigated the mechanism by which RANKL expression is induced
      by MIP-1alpha and the effects of MIP-1alpha on the activation of osteoclasts.
      RANKL mRNA and RANKL protein expressions increased in both ST2 cells and MC3T3-E1
      cells in a MIP-1alpha concentration-dependent manner. RANKL mRNA expression began
      to increase at 1 h after the addition of MIP-1alpha; the increase became
      remarkable at 2 h, and continuous expression was observed subsequently. Both ST2
      and MC3T3-E1 cells showed similar levels of increased RANKL protein expression at
      1, 2, and 3 days after the addition of MIP-1alpha. After the addition of MIP
      1alpha, the amount of phosphorylated ERK1/2 and Akt protein expressions showed an
      increase, as compared to the corresponding amount in the control group. On the
      other hand, the amount of phosphorylated p38MAPK protein expression showed a
      decrease from the amount in the control group after the addition of MIP-1alpha.
      U0126 (a MEK1/2 inhibitor) or LY294002 (a PI3K inhibitor) was added to ST2 and
      MC3T3-E1 cells, and was found to inhibit RANKL mRNA and RANKL protein expression
      in these cells. When SB203580, a p38MAPK inhibitor, was added, RANKL mRNA and
      RANKL protein expression were increased in these cells. MIP-1alpha was found to
      promote osteoclastic differentiation of C7 cells, an osteoclastic precursor cell
      line, in a MIP-1alpha concentration-dependent manner. MIP-1alpha promoted
      differentiation into osteoclasts more extensively in C7 cells incubated together
      with ST2 and MC3T3-E1 cells than in C7 cells incubated alone. These results
      suggested that MIP-1alpha directly acts on the osteoclastic precursor cells and
      induces osteoclastic differentiation. This substance also indirectly induces
      osteoclastic differentiation through the promotion of RANKL expression in bone
      marrow stromal cells and osteoblasts. The findings of this investigation
      suggested that activation of the MEK/ERK and the PI3K/Akt pathways and inhibition
      of p38MAPK pathway were involved in RANKL expression induced by MIP-1alpha in
      bone-marrow stromal cells and osteoblasts. This finding may be useful in the
      development of an osteoclastic inhibitor that targets intracellular signaling
      factors.

PMID- 17549608
TI  - Effect of aging on the expression of intracellular Ca(2+) transport proteins in a
      rat heart.
AB  - Aging process is accompanied by various biological dysfunctions including altered
      calcium homeostasis. Modified calcium handling might be responsible for changed
      cardiac function and potential development of the pathological state. In the
      present study we compared the mRNA and protein levels of the intracellular Ca(2+)
      handling proteins--inositol 1,4,5-trisphosphate receptor (IP(3)R), ryanodine
      receptor (RyR), sarcoplasmic reticulum Ca(2+) pump (SERCA2), and also transient
      receptor potential C (TRPC) channels in cardiac tissues of 5-, 15-, and 26-month
      old rats. Aging was accompanied by significant increase in the mRNA levels of
      IP(3)R and TRPC channels in both ventricles and atria, but mRNA level of the type
      2 RyR was unchanged. Protein content of the IP(3)R1 correlated with mRNA levels,
      in the left ventricle of 15- and 26-month-old rats the value was approximately
      1.8 and 2.8-times higher compared to 5-month-old rats. No significant differences
      were observed in mRNA and protein levels of the SERCA2 among 5-month-old and aged
      rats. However, Ca(2+)-ATPase activity significantly decreased with age,
      activities in 5-, 15-, and 26-month-old rats were 421.2 +/- 13.7, 335.5 +/- 18.1
      and 304.6 +/- 14.8 nmol P(i) min(-1) mg(-1). These results suggest that altered
      transporting activity and/or gene expression of Ca(2+)-handling proteins of
      intracellular Ca(2+) stores might affect cardiac function during aging.

PMID- 17549609
TI  - Effect of non-enzymatic glycation on esterase activities of hemoglobin and
      myoglobin.
AB  - Heme proteins--hemoglobin and myoglobin possess esterase activities. Studies with
      purified hemoglobin from normal individuals and diabetic patients revealed that
      the esterase activity as measured from hydrolysis of p-nitrophenyl acetate (p
      NPA) was higher in diabetic condition and increased progressively with extent of
      the disease. HbA(1c), the major glycated hemoglobin, which increases
      proportionately with blood glucose level in diabetes mellitus, exhibited more
      esterase activity than the non-glycated hemoglobin fraction, HbA(0), as
      demonstrated spectrophotometrically as well as by activity staining. Glycation
      influenced esterase activity of hemoglobin by increasing the affinity for the
      substrate and the rate of the reaction. Both HbA(0) and HbA(1c)-mediated
      catalysis of p-NPA hydrolysis was pH-dependent. Esterase activity of in vitro
      glycated myoglobin (GMb) was also higher than that of its non-glycated analog
      (Mb). The amplified esterase activities of hemoglobin and myoglobin might be
      associated with glycation-induced structural modifications of the proteins.

PMID- 17549610
TI  - MTA family of transcriptional metaregulators in mammary gland morphogenesis and
      breast cancer.
AB  - Since breast cancer and its associated metastasis are a global health problem and
      a major cause of mortality among women, research efforts to understand the
      development, morphogenesis, and functioning of the mammary gland are a high
      priority. Myriad signaling pathways, transcription factors, and associated
      transcriptional coregulators have been identified in both normal functioning and
      neoplastic transformation of the mammary gland. The discovery of the metastasis
      tumor antigen 1 (MTA1) gene, its overexpression in cancer and metastasis and its
      subsequent identification as an integral part of the chromatin remodeling complex
      heralded extensive research on its physiological role. Subsequent identification
      of additional gene family members, namely MTA1s, MTA2, and MTA3, and their
      functions in the cell has resulted in the establishment of the significance of
      the MTA family. The role of these proteins in modulating hormonal responses in
      normal mammary glands and in breast cancer has resulted in their identification
      as important molecular markers and potential therapeutic targets.

PMID- 17549611
TI  - Modeling migration and metastasis in Drosophila.
AB  - Cell motility makes essential contributions to normal embryonic development and
      homeostasis. It is also thought to contribute in important ways to tumor
      metastasis. Because of this dual importance, cell migration has been extensively
      studied. The fruit fly Drosophila melanogaster has served as an important model
      organism for genetic analysis of many aspects of developmental biology, including
      cell migration. Here we describe the various types of cell movements that have
      been studied in detail, which represent models for epithelial-to-mesenchymal
      transition, transepithelial migration, inflammation, wound healing and invasion.
      We summarize what has been learned about the molecular control of cell migration
      from genetic studies in the fly. In addition, we describe recent efforts to model
      tumor metastasis directly in Drosophila by expressing oncogenes and/or mutating
      tumor suppressor genes. Together these studies suggest that Drosophila has much
      to offer as a model for varied aspects of tumor metastasis.

PMID- 17549612
TI  - Fluorescence modulation of acridine and coumarin dyes by silver nanoparticles.
AB  - Silver nanoparticles were synthesized by chemical reduction of silver ions by
      sodium borohydride in the presence of poly-(N)-vinyl-2-pyrrolidone in solution of
      short chain alcohols. The nanoparticles are stable in 2-propanol, and the average
      diameter of the Ag colloid obtained in this solvent is about 6 nm. The
      photophysical properties of acridinium and coumarin dyes in 2-propanol are
      affected by the presence of silver nanoparticles. The interaction of silver
      nanoparticles with acridinium derivative leads to a spectral change of its
      intramolecular charge transfer (ICT) absorption band. The dye emission increases
      suddenly with the initial addition of the Ag metal nanoparticles, but at a high
      concentration of the colloid, static fluorescence quenching occurs with a
      progressive decrease of the fluorescence efficiency. Amino coumarin fluorescence
      is only quenched by the silver nanoparticles in solution.

PMID- 17549613
TI  - The impact of breast cancer genetic risk assessment on intentions to perform
      cancer surveillance behaviors.
AB  - One hundred and fifty-four women undergoing breast/ovarian cancer genetic risk
      assessment completed questionnaires at entry into the Cancer Genetic Service for
      Wales (CGSW) assessment program and following risk provision, mapping the
      strength of intentions to engage in a number of preventive/surveillance
      behaviors, including seeing specialists, breast self-examination, and involvement
      in screening programs, including mammography. A number of potential predictors of
      intentions were also assessed, including participants' mood and emotional
      response to receiving risk information, the perceived benefits (in terms of
      reassurance and early disease detection) of engaging in each preventive behavior,
      and the perceived desires of their family and General Practitioner. Intentions to
      self-examine did not change following risk provision, although strength of
      intentions to engage in some other preventive behaviors did lessen. Family and
      General Practitioners appeared to be strong social influences on behavioral
      intentions, as were the perceived benefits of gaining reassurance and/or early
      detection of disease.

PMID- 17549614
TI  - Impact of the HealthChoice program on cesarean section and vaginal birth after C
      section deliveries: a retrospective analysis.
AB  - OBJECTIVE: To assess the impact of the HealthChoice program in Maryland on
      cesarean section and vaginal birth after C-section deliveries. STUDY DESIGN: Pre
      post design using a comparison group with Maryland State Inpatient Databases,
      part of the Healthcare Cost and Utilization Project, developed by the Agency for
      Healthcare Research and Quality. Although the combined 1995 and 2000 database
      contained over 1.2 million inpatient discharge records, the analysis included all
      hospital discharge abstracts for women in labor. To identify the delivery,
      Diagnoses-Related Groups (DRGs) 370-375 were used from the discharge data.
      Together, there were 128,743 births identified in both years. METHODS: Pregnant
      women enrolled in Medicaid managed care were compared pre-implementation and post
      implementation with pregnant women delivering babies under private insurance. The
      analysis computed difference-in-differences estimates using a logistic regression
      model that controlled for maternal characteristics, payment source, labor and
      delivery complications, and hospital characteristics. The outcome variables
      included Primary Cesarean, Repeat Cesarean, and Vaginal Birth after C-section.
      RESULTS: These results suggest that Medicaid managed care enrollees were less
      likely to undergo cesarean section deliveries relative to privately insured
      beneficiaries. Medicaid MCOs may have done a better job of limiting the growth in
      overused procedures than did MCOs and providers for privately insured women.
      CONCLUSION: This study has shown that there has been an overall increase in the
      use of primary and repeat cesarean sections in Maryland hospitals. However,
      HealthChoice limited this increase for Medicaid enrollees relative to privately
      insured women. On the other hand, vaginal births after C-section have declined in
      Maryland.

PMID- 17549615
TI  - An exploration of maternal intimate partner violence experiences and infant
      general health and temperament.
AB  - OBJECTIVES: While the women's health consequences of intimate partner violence
      have received much research attention, less is known about how maternal abuse
      experiences affect infant health and well-being. Existing studies have also been
      unable to examine specific types of intimate partner violence such as
      psychological aggression, physical abuse, and sexual coercion. This secondary
      data analysis explored the prevalence, patterns, and types of intimate partner
      violence within a large cohort of mothers and explored the relationship between
      maternal intimate partner violence experiences and infant's general health and
      temperament at 1 year of age. METHODS: Existing data were drawn from the Fragile
      Families and Child Wellbeing study which collected data through surveys conducted
      shortly after the infant's birth (baseline) and at 1 year of age (follow-up).
      Records from 4,141 mothers recruited from 75 hospitals, in 20 cities, in the US
      were used. Bivariate and multivariate regression analyses were conducted.
      RESULTS: Results show high rates of intimate partner violence. Maternal reports
      of any intimate partner violence at baseline or follow-up were both significantly
      associated with increased odds of less than excellent infant general health and
      difficult temperament. Independent examination of psychological, physical, and
      sexual abuse revealed differential relationships between the types of intimate
      partner violence and infant health outcomes. CONCLUSIONS: Results from this study
      contribute to our understanding of the infant health threats associated with
      maternal intimate partner violence experiences. Additional research addressing
      the complex relationship between maternal abuse experiences and infant health and
      specific intervention implications is warranted.

PMID- 17549616
TI  - Feasibility and utility of screening adolescent mothers for Chlamydia at their
      children's health care visits.
AB  - PURPOSE: Assess the feasibility of offering and barriers to accepting urine-based
      screening for Chlamydia trachomatis (CT) among asymptomatic adolescent mothers
      during their children's health care visits. METHOD: Providers were automatically
      cued to offer CT-screening to 13 through 21 year old mothers when they opened the
      child's medical record. Recording the mothers' screening decisions removed the
      flag for 6 months. Providers were also prompted to assess the perceived
      importance of CT prevention, likelihood of having CT, and the worst aspect of
      having CT. RESULTS: Mothers usually brought their children to the clinic. Hence,
      providers could act on 97% of the 318 flags they saw. They responded
      appropriately 75% of the time. Only 96 (42%) of the 229 mothers who were asked
      agreed to screening. The primary reasons for declining were "monogamous" and
      "tested within 6 months". Almost everyone said CT was a top preventive health
      priority, but that they would be surprised if they were infected. Mothers who
      agreed to screening were less likely to have a child less than 6 months of age
      (26.0% vs. 57.1%; P < 0.0001). They were also more likely to rate knowledge of
      partner infidelity (39.4% vs. 13.6%; P = 0.03) and less likely to rate medical
      problems (15.2% vs. 40.9%; P = 0.01) the worst aspect of having CT. None of the
      21 urine samples obtained within 6 months of delivery were positive for CT.
      Thereafter, 5 (9.1%) of the 55 urines were positive. CONCLUSIONS: It is feasible
      and useful to screen adolescent mothers for CT at their children's health care
      visits. The best way to increase the efficacy and strengthen the impact of urine
      based CT-screening in this setting is to initiate testing after the 6th
      postpartum month and heighten awareness of STD-risk among adolescent mothers.

PMID- 17549617
TI  - Recognition of immaturity and emotional expressions in blended faces by children
      with autism and other developmental disabilities.
AB  - The recognition of facial immaturity and emotional expression by children with
      autism, language disorders, mental retardation, and non-disabled controls was
      studied in two experiments. Children identified immaturity and expression in
      upright and inverted faces. The autism group identified fewer immature faces and
      expressions than control (Exp. 1 & 2), language disordered (Exp. 1), and mental
      retardation (Exp. 2) groups. Facial inversion interfered with all groups'
      recognition of facial immaturity and with control and language disordered groups'
      recognition of expression. Error analyses (Exp. 1 & 2) showed similarities
      between autism and other groups' perception of immaturity but differences in
      perception of expressions. Reasons for similarities and differences between
      children with and without autism when perceiving facial immaturity and expression
      are discussed.

PMID- 17549618
TI  - Physiological mechanisms involved in religiosity/spirituality and health.
AB  - During the last two decades of the 20th century, psychological science
      rediscovered religiosity/spirituality (R/S) as a legitimate subject matter in
      understanding the human experience. In large measure, this renewed interest was
      motivated by the positive association between this variable and health (physical
      and mental) reported in much of the literature. If the described relationship
      between R/S and health is accurate, the question of how such an influence might
      be realized becomes important and subject to empirical investigation. The present
      paper develops a rationale for why such an outcome might be expected and
      describes various physiological mechanisms that could mediate the effect of R/S
      on health.

PMID- 17549619
TI  - Responses to depression in children: reconceptualizing the relation among
      response styles.
AB  - We propose that researchers should utilize ratio scores when examining the
      response styles theory rather than examine each of the response styles
      separately. Higher ratio scores indicate a higher probability of engaging in
      ruminative, as opposed to distracting and problem solving, behaviors. In Phase
      One, we examined the factor structure and reliability of the Children's Response
      Styles Questionnaire (CRSQ) in a sample of 287 third through sixth grade
      schoolchildren. A two factor solution was obtained: (1) Rumination and (2)
      Distraction and Problem Solving. Both factors exhibited strong psychometric
      properties. In Phase Two, 140 children completed the CRSQ and the Children's
      Depression Inventory (CDI). Six weeks later, children completed the CDI.
      Confirmatory factor analysis indicated that the two-factor solution fit the data
      well. In line with hypotheses, CRSQ ratio scores were more strongly associated
      with CDI residual change scores than were either CRSQ rumination or distraction
      and problem solving scores.

PMID- 17549620
TI  - Joint attention and attachment in toddlers with autism.
AB  - Joint attention is often referred to as a triadic relation between self, other
      and object. Young children with autism show deficiencies in the use of joint
      attention behaviors. Individual differences may be expected, and they may be
      determined by the children's cognitive development or the characteristics of the
      relationship of the child with the caregiver. Although most joint attention
      skills develop under the age of three, most studies of joint attention in
      children with autism involved children older than 3 years of age, due to
      difficulties in diagnosing autism under this age. In this study we investigated
      joint attention behaviors of 78 young children (mean age 25.7 months, SD 6.1)
      with autism spectrum disorders (n = 20), other developmental delays (n = 18), and
      typically developing children (n = 40). Following the pertinent literature and
      confirmed by factor analysis, two types of joint attention behaviors were
      distinguished, Basic Joint Attention (BJA) and Associated Joint Attention (AJA).
      We found that cognitive delays and autistic symptoms-but not attachment
      insecurity or disorganization-were related to less joint attention. Already at
      the age of 2 years, children with more autistic symptoms show less joint
      attention, even after controlling for developmental level.

PMID- 17549621
TI  - A dynamic systems analysis of parent-child changes associated with successful
      "real-world" interventions for aggressive children.
AB  - Studies have shown that improved parenting mediates treatment outcomes for
      aggressive children, but we lack fine-grained descriptions of how parent-child
      interactions change with treatment. The current study addresses this gap by
      applying new dynamic systems methods to study parent-child emotional behavior
      patterns. These methods tap moment-to-moment changes in interaction processes
      within and across sessions and quantify previously unmeasured processes of change
      related to treatment success. Aggressive children and their parents were
      recruited from combined Parent Management Training and Cognitive-behavioral
      programs in "real world" clinical settings. Behavioral outcomes were assessed by
      reports from parents and clinicians. At pre- and post-treatment, home visits were
      videotaped while parents and children discussed consecutively: a positive topic,
      a mutually unresolved problem, and another positive topic. Results showed that
      significant improvements in children's externalizing behavior were associated
      with increases in parent-child emotional flexibility during the problem-solving
      discussion. Also, dyads who improved still expressed negative emotions, but they
      acquired the skills to repair conflicts, shifting out of their negative
      interactions to mutually positive patterns.

PMID- 17549622
TI  - Risk factors for boy's conduct problems in poor and lower-middle-class
      neighborhoods.
AB  - The joint trajectory analysis version of Nagin's (Group-based modeling of
      development. Cambridge, MA: Harvard University Press, 2005) semiparametric, group
      based approach for modeling trajectories was used to assess how boy's
      trajectories of conduct problems (CP) and neighborhood SES covaried from ages 5
      to 12. Participants were recruited from Women, Infants, and Children clinics when
      they were 18 months old. Subsequent analyses examined whether boys from poor and
      more prosperous neighborhoods differed in the degree to which they were exposed
      to familial risk factors for CP during early childhood and the extent to which
      risk factors for CP were generalizable across communities. Findings revealed a
      small, but positive relationship, between boy's trajectories of CP and
      neighborhood SES. In addition, chronic CP boys from more prosperous communities
      were found to have more child/individual risk factors for CP than their
      counterparts from poorer communities. Implications for prevention and
      intervention are discussed.

PMID- 17549623
TI  - Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE): biochemical
      features and therapeutic approaches.
AB  - Over the last 15 years, important research has expanded our knowledge of the
      clinical, molecular genetic, and biochemical features of mitochondrial
      neurogastrointestinal encephalomyopathy (MNGIE). The characterization of
      mitochondrial involvement in this disorder and the seminal determination of its
      genetic cause, have opened new possibilities for more detailed and deeper studies
      on the pathomechanisms in this progressive and fatal disease. It has been
      established that MNGIE is caused by mutations in the gene encoding thymidine
      phosphorylase (TP), which lead to absolute or nearly complete loss of its
      catalytic activity, producing systemic accumulations of its substrates, thymidine
      (dThd) and deoxyuridine (dUrd). Findings obtained from in vitro and in vivo
      studies indicate that the biochemical imbalances specifically impair
      mitochondrial DNA (mtDNA) replication, repair, or both leading to mitochondrial
      dysfunction. We have proposed that therapy for MNGIE should be aimed at reducing
      the concentrations of these toxic nucleosides to normal or nearly normal levels.
      The first treatment, allogeneic stem-cell transplantation (alloSCT) reported in
      2006, produced a nearly full biochemical correction of the dThd and dUrd
      imbalances in blood. Clinical follow-up of this and other patients receiving
      alloSCT is necessary to determine whether this and other therapies based on a
      permanent restoration of TP will be effective treatment for MNGIE.

PMID- 17549624
TI  - Genetic divergence detected by ISSR markers and characterization of
      microsatellite regions in Mytilus mussels.
AB  - The wide distribution of microsatellites in mussels of the Mytilus edulis complex
      (Mytilidae) enables the analysis of inter-simple-sequence repeat (ISSR) markers.
      The aim of this investigation was to assess genetic differentiation in six
      sampling localities distributed along the European Atlantic coast to expose the
      potential of these markers in genetic studies requiring the detection of low
      polymorphism and as a source of sequences for developing microsatellite markers.
      We detected low genetic structuring within each member of the Mytilus edulis
      complex. Nei and Li distances and AMOVA clustered the individuals studied into
      two groups. On the basis of these results two sampling localities coming from the
      M. edulis x M. galloprovincialis mosaic hybrid zone in Western Europe were
      assigned to one species. On the other hand, mussels of a sampling locality in the
      Baltic Sea were not significantly different from a pure M. edulis locality
      supporting an extensive introgression of M. edulis in these individuals. Finally,
      148 microsatellites were found in the sequences of 51 ISSR markers, and two
      polymorphic microsatellite markers were developed.

PMID- 17549625
TI  - Is BRCA2 c.9079 G>A a predisposing variant for early onset breast cancer?

PMID- 17549626
TI  - Quantitative hypermethylation of a small panel of genes augments the diagnostic
      accuracy in fine-needle aspirate washings of breast lesions.
AB  - PURPOSE: We hypothesized that comprehensive breast cancer methylation profiling
      might provide biomarkers for diagnostic assessment of suspicious breast lesions
      using fine needle aspiration biopsy (FNA). EXPERIMENTAL DESIGN: Twenty-three gene
      promoters were surveyed by quantitative methylation-specific PCR in bisulfite
      modified DNA from 66 breast carcinomas (BCa), 31 fibroadenomas (FB) and 12 normal
      breast (NT) samples to define a set of genes differentially methylated in
      malignant and non-malignant tissues. This set was tested in 78 FNA washings
      obtained pre-operatively (66 malignant, 12 benign), with histopathological
      diagnosis. Receiver operator characteristic (ROC) curve analysis identified a
      gene panel which might distinguish cancer from non-cancerous lesions. Finally,
      this panel was validated in an independent series of FNA washings (45 cases) in
      which cytomorphology did not reach definitive diagnosis. RESULTS: In tissue
      samples, 14-3-3-sigma, DAPK, CCND2, RASSF1A, CALCA, APC, HIN1, RARbeta2, TIG1,
      and GSTP1 methylation levels differed significantly among BCa, FB, and NT. ROC
      curve analysis identified a panel of four gene loci (CCND2, RASSF1A, APC, and
      HIN1) that discriminated BCa from benign lesions in a set of 78 FNA washings from
      histologically characterized breast lesions. When this panel was tested in the
      validation dataset of 45 FNA washings, breast cancer was identified with perfect
      specificity (100%) when 3 of 4 gene loci tested positive, providing estimated
      added information of 91% over cytomorphologic evaluation alone. CONCLUSIONS: Our
      data provide evidence that multigene methylation analysis augments diagnostic
      accuracy of cytological assessment of suspicious breast lesions, and might be a
      valuable ancillary tool for breast cancer diagnosis.

PMID- 17549627
TI  - Effect of hypothalamic proline-rich peptide (PRP-1) on neuronal and bone marrow
      cell apoptosis.
AB  - The AGAPEPAEPAQPGVY proline-rich peptide (PRP-1) was isolated from neurosecretory
      granules of the bovine neurohypophysis; it is produced by N. supraopticus and N.
      paraventricularis. It has been shown that PRP-1 has many potentially beneficial
      biological effects including immunoregulatory, hematopoietic, antimicrobial and
      anti-neurodegenerative properties. Here we investigated the influence of PRP-1 on
      staurosporine-induced apoptosis of postnatal hippocampal cells and on doxorubicin
      induced bone marrow granulocyte- and monocyte apoptosis. The intention was to
      further characterize the effect of PRP-1 on the survival rate of neurons and in
      context with myelopoiesis. We demonstrate that PRP-1 significantly reduced
      apoptosis of postnatal hippocampal cells induced by staurosporine. The protective
      effect of PRP-1 against apoptotic cell death was shown to be both time- and dose
      dependent. Neuroprotection was more pronounced after prolonged pretreatment of
      the cells with PRP-1 before the induction of apoptosis with staurosporine. The
      related peptide [arg(8)]vasopressin did not reveal neuroprotection. PRP-1 also
      significantly reduced apoptosis of bone marrow monocytes and granulocytes induced
      by doxorubicin. This protective effect lasted for 2-4 h and was not detectable
      anymore after 24 h when PRP-1 and doxorubicin were added simultaneously.
      Previously obtained data and results of the current studies suggested that the
      hypothalamic PRP-1 possibly represents an endogenous peptide whose primary
      functions are to regulate myelopoiesis and neuron survival as we provide evidence
      that PRP can differentially reduce both staurosporine- and doxorubicin-induced
      hippocampal and bone marrow cell apoptosis.

PMID- 17549628
TI  - Involvement of nitric oxide in spatial memory deficits in status epilepticus
      rats.
AB  - Status epilepticus (SE) is associated with a significant risk of cognitive
      impairment, and the increase of nitric oxide (NO) releasing has been reported
      during SE. We investigated the effects of neuronal nitric oxide synthase (nNOS)
      inhibitor, 7-nitroindazole (7-NI) and inducible nitric oxide synthase (iNOS)
      inhibitor, aminoguanidine (AG), on spatial performance of rats in the Morris
      water maze. Treatment with 7-NI, but not with AG, improved the performance of
      rats after SE not only in acquisition of the task but also in probe test.
      Furthermore, the level of SE-induced malondialdehyde (MDA), end product of lipid
      peroxidation, was significantly decreased only in animals receiving 7-NI
      injection. Taken together, the results of the present study provided evidence
      that the NO pathway contributed to oxidative stress after SE, and nNOS/NO pathway
      may underlie one of the potential mechanisms contributing to SE-induced spatial
      memory deficits.

PMID- 17549629
TI  - Protective effects of baicalin and octreotide on multiple organ injury in severe
      acute pancreatitis.
AB  - PURPOSE: To discuss the application value of Baicalin which is a new drug by
      comparing the protecting effects of Baicalin and Octreotide on multiple organs
      (pancreas, liver, kidney, and lung) in Severe acute pancreatitis (SAP). METHODS:
      The improved Aho method was adopted to prepare SAP rat models via retrograde
      injection of 3.5% sodium taurocholate to the pancreatic duct. The 135 SAP rat
      models after being prepared were randomly divided into the model group, Baicalin
      treatment group and Octreotide treatment group with 45 rats in each group;
      another 45 were selected to be the sham operation group, which only received
      abdomen opening surgery. The groups were then randomly divided into 3 h, 6 h and
      12 h groups with 15 rats in each group, 10 min after successful modeling, the
      Baicalin treatment group was first injected with a 5% Baicalin injection at a
      dose of 10 mg/100 g via external jugular-vein passage followed by continuous
      intravenous administration (10 mg/h/100 g) by microinfusion pump; the Octreotide
      treatment group was first injected by Octreotide at a dose of 0.2 ug/100 g via
      external jugular-vein passage followed by continuous intravenous transfusion (10
      mg/h/100 g) by microinfusion pump at a transfusion speed of 0.2 ug/h/100 g. The
      sham operation group and model group were injected with saline of equivalent
      volume at the corresponding time points after operation. The following
      observations were carried out 3, 6 and 12 h after operation: (1) mortalities of
      all rat groups followed by batch execution of rats and observation of the gross
      pathological changes of multiple organs; (2) observation of the pathological
      changes of multiple organ samples fixed according to the relevant requirements
      after HE staining; and (3) serum content of amylase, NO, malonaldehyde (MDA), and
      tumor necrosis factor alpha (TNF-alpha). RESULTS: (1) The survival rate of the
      sham operation group and all treatment groups was 100%, whilst the 12 h survival
      of the model group was 66.67% (10/15), indicating a significant difference (P <
      0.05). (2) The gross pathological changes and changes under light microscopy of
      multiple organs aggravated with time after modeling. The pathological changes of
      all treatment groups were milder than those of the model group at different time
      points by various degrees, most obviously at 6 h and 12 h. The gross pathological
      changes showed a similarity between the Octreotide and Baicalin treatment groups
      in terms of the pathological changes of pancreatic tissue. The therapeutic
      effects of Octreotide on kidney and lung were superior to those in the Baicalin
      treatment group while the pathological manifestations of the Baicalin treatment
      group were superior to those of the Octreotide treatment group. (3) There was no
      marked difference between the Baicalin and Octreotide treatment groups in terms
      of plasma amylase levels at all time points (P > 0.05). Although the plasma
      amylase levels of the Baicalin treatment group were lower than those of the model
      group at all time points, the levels in the Baicalin treatment group were
      significantly lower than those in the model group only at 3 h (P < 0.05), and
      there was no marked difference in the levels between the Baicalin treatment group
      and model groups at 6 and 12 h (P > 0.05); the levels in the Octreotide treatment
      group were significantly lower than in the model group at 6 h (P < 0.05), and
      there was no marked difference between the levels in the Octreotide treatment
      group and model group at 3 h and 12 h (P > 0.05). (4) The serum NO contents of
      the Baicalin treatment group were significantly lower than those of the model
      group (P < 0.05), while in the Octreotide treatment group it was obviously lower
      than in the model group at 3 and 12 h (P < 0.01); in this regard there was no
      marked difference between the Baicalin and Octreotide treatment groups at
      different time points (P > 0.05). (5) The serum MDA contents of the Baicalin
      treatment group were significantly lower than those of the model group (P <
      0.01), while in the Octreotide treatment group it was significantly less than the
      model group at 6 and 12 h (P < 0.05), and in the Baicalin treatment group was
      significantly less than in the Octreotide treatment group at 12 h (P < 0.05). (6)
      There was no marked difference among the model group, Baicalin treatment group
      and Octreotide treatment group in terms of serum TNF-alpha content at 3 h and 12
      h (P > 0.05). At 6 h the value in the Baicalin treatment group was significantly
      less than in the model group (P < 0.001), in the Octreotide treatment group it
      was significantly less than in the model group (P < 0.001), and the Octreotide
      treatment group it was significantly less than in the Baicalin treatment group (P
      < 0.01). CONCLUSIONS: Both Baicalin and Octreotide have obvious protective
      effects on the multiple organ injury in SAP with mechanisms associated to
      manifold factors. By comparing the pharmacologic effects of Octreotide and
      Baicalin, we believe that Baicalin as a new drug has a protective effect on
      multiple organs of a SAP rat model similar to that of Octreotide and is worth
      further study and development.

PMID- 17549630
TI  - Helicobacter pylori infection induces candidate stem cell marker Musashi-1 in the
      human gastric epithelium.
AB  - Musashi-1 (Msi-1), a mammalian neural RNA-binding protein, has been found to play
      important roles in the maintenance of stem cell states and differentiation in
      neural stem cells and mouse intestinal cells. We explored Msi-1 expression and
      its potential implications in the human stomach. Reverse transcription-PCR
      revealed that Msi-1 levels were significantly higher in the corpus than in antrum
      in Helicobacter pylori (Hp)-infected patients (n = 49) (P < 0.00001) in paired
      biopsy samples, whereas they were low and comparable at these two sites in Hp
      negative patients (n = 31). Msi-1 levels were significantly higher in the Hp
      infected corpus (n = 107) than in the Hp-negative corpus (n = 69) (P <
      0.00000001). Immunohistochemistry and in situ hybridization demonstrated that Msi
      1 was expressed at the base and neck/isthmus region of the fundic glands and
      partly co-expressed in Ki-67-positive cells in the corpus and antrum. Msi-1
      levels correlated with Hp density (P < 0.05). Based on these results, we conclude
      that Hp infection strongly induces Msi-1 in the corpus. Given its expression in
      dividing cells, Msi-1 may modulate the state of gastric progenitor cells.

PMID- 17549631
TI  - Development of functional diarrhea, constipation, irritable bowel syndrome, and
      dyspepsia during and after traveling outside the USA.
AB  - BACKGROUND: Persistent gastrointestinal (GI) symptoms after travel abroad may be
      common. It remains unclear how often subjects who developed new GI symptoms while
      abroad have persistent symptoms on return. The objective of this retrospective
      study was to evaluate the prevalence of persistent GI symptoms in a healthy
      cohort of travelers. METHODS: One hundred and eight consecutive patients, mostly
      returned missionaries, attending the University of Utah International Travel
      Clinic for any reason (but mostly GI symptoms) had data recorded about their
      bowel habits before, during, and after travel abroad. All subjects had standard
      hematological, biochemical, and microbiological tests to exclude known causes of
      their symptoms. Endoscopic procedures were performed when considered necessary by
      the treating physician. Diarrhea, constipation, irritable bowel syndrome (IBS),
      bloating, and dyspepsia were defined according to the Rome II Criteria. RESULTS:
      Eighty three (82% men and 18% women, median age 21 years) completed the survey
      with 68 subjects completing the questionnaire about bowel habits before and
      during travel. Among the respondents, 55 (82.1%) did not have any symptoms before
      travel. During travel, 41 (63%) developed new onset diarrhea; 6 (9%) developed
      constipation; 16 (24%) IBS, 29 (45%) bloating; and 11 (16%) dyspepsia. Of those
      who developed symptoms during travel, 27 (68%) had persistent diarrhea, 3 (50%)
      had persistent constipation, 10 (63%) had persistent IBS, 12 (43%) had persistent
      bloating and 8 (73%) had persistent dyspepsia. The presence of bowel symptoms
      during and after travel was not associated with age, gender, travel destination,
      or duration of travel. CONCLUSIONS: This study suggests that new onset of
      diarrhea, IBS, constipation, and dyspepsia are common among subjects traveling
      abroad. Gastrointestinal symptoms that develop during travel abroad usually
      persist on return.

PMID- 17549632
TI  - Chronic hepatitis C virus and celiac disease, is there an association?
AB  - Celiac disease (CD) has been epidemiologically associated with chronic hepatitis
      C (HCV), and CD activation after the initiation of interferon (IFN-alpha) in
      patients with HCV is documented. However, clear association of CD and HCV is
      lacking. A prospectively maintained database of 878 CD patients showed a
      prevalence of 0.68% (six patients). Symptoms of diarrhea, weight loss, and
      depression prompted the diagnosis of CD during or after IFN-alpha therapy in four
      cases. Also, 294 subjects with liver disease (195 with HCV, 80 normal controls
      and 19 disease controls) were prospectively screened for CD. The mean age of the
      subjects was 50.1 years (SD 12.3), 58% males:42% females. A total of 30% received
      IFN-alpha therapy (16% at the time of testing for CD). Two HCV patients (1%) had
      positive tTG-IgA but these had negative endomysial antibody (EMA) and normal
      duodenal biopsies. CD prevalence is not increased in patients with HCV. Routine
      screening of CD in HCV patients is not warranted, however, the presence of CD
      should be considered in the setting of clinical deterioration during or after IFN
      alpha therapy.

PMID- 17549633
TI  - Serum interleukin-6, soluble interleukin-6 receptor and Crohn's disease activity.
AB  - The relationship between plasma interleukin-6 (IL-6) concentration and its
      soluble receptor in Crohn's disease (CD) is not well elucidated. Twenty healthy
      volunteers and 94 consecutive patients with CD (44 in relapse and 50 in
      remission) were studied. Plasma IL-6 concentrations in patients with active
      disease [80 +/- 9 pg/ml; mean +/- standard error of the mean (SEM)] were
      significantly higher than in patients with inactive disease (50 +/- 4 pg/ml; P <
      0.001) or controls (3 +/- 1 pg/ml; P < 0.001). However, concentrations did not
      vary with the severity of CD attacks. Plasma concentrations of soluble
      interleukin-6 receptor (sIL-6R) in active-CD patients (77 +/- 5 ng/ml) did not
      differ significantly from those with inactive disease (82 +/- 5 ng/ml), while
      both groups had significantly raised concentrations compared with those of
      controls (58 +/- 6 ng/ml; P < 0.03 and P < 0.01, respectively). Plasma IL-6
      concentrations correlated significantly with serum C-reactive protein (CRP) (r =
      0.34; P < 0.001), whereas plasma sIL-6R concentrations did not. Taken together,
      these data suggest that, although IL6 and sIL6-R are both involved in the
      inflammatory process of CD, they are poor markers of disease activity.

PMID- 17549634
TI  - Regional esophageal dysfunction in scleroderma and achalasia using multichannel
      intraluminal impedance and manometry.
AB  - BACKGROUND: Achalasia and scleroderma are esophageal motility abnormalities
      characterized by severely impaired bolus transit. Combined multichannel
      intraluminal impedance and manometry (MII-EM) enables the simultaneous
      measurement of intraesophageal pressures and bolus transit at various levels
      within the esophagus. AIM: The aim of the study was to evaluate and characterize
      regional pressure and transit profile differences in scleroderma and achalasia
      patients. METHODS: A retrospective analysis was carried out of MII-EM studies of
      patients with scleroderma (15), achalasia (20), and poorly relaxing lower
      esophageal sphincter (LES) with normal esophageal body function (20) as a control
      group. Bolus presence and segmental transit were evaluated by MII. RESULTS: In
      patients with achalasia, bolus transit was impaired across all four sites
      compared with scleroderma (P < 0.0125) even though distal esophageal pressures
      were higher (P < 0.05) in patients with achalasia. Pressures in patients with
      achalasia were similar across all four sites (ANOVA; saline, P = 0.373; viscous,
      P = 0.615). Bolus clearance rates and contraction amplitudes in patients with
      scleroderma decreased from proximal to distal. In the control group, bolus
      clearance was complete during > or = 83% of all swallows and esophageal pressure
      amplitudes increased distally. CONCLUSION: While the overall bolus transit is
      impaired in both patients with achalasia and scleroderma regional pressure and
      bolus transit differences exist. Bolus transit abnormalities result from abnormal
      esophageal body contraction and not abnormal LES relaxation.

PMID- 17549635
TI  - How many imputations are really needed? Some practical clarifications of multiple
      imputation theory.
AB  - Multiple imputation (MI) and full information maximum likelihood (FIML) are the
      two most common approaches to missing data analysis. In theory, MI and FIML are
      equivalent when identical models are tested using the same variables, and when m,
      the number of imputations performed with MI, approaches infinity. However, it is
      important to know how many imputations are necessary before MI and FIML are
      sufficiently equivalent in ways that are important to prevention scientists. MI
      theory suggests that small values of m, even on the order of three to five
      imputations, yield excellent results. Previous guidelines for sufficient m are
      based on relative efficiency, which involves the fraction of missing information
      (gamma) for the parameter being estimated, and m. In the present study, we used a
      Monte Carlo simulation to test MI models across several scenarios in which gamma
      and m were varied. Standard errors and p-values for the regression coefficient of
      interest varied as a function of m, but not at the same rate as relative
      efficiency. Most importantly, statistical power for small effect sizes diminished
      as m became smaller, and the rate of this power falloff was much greater than
      predicted by changes in relative efficiency. Based our findings, we recommend
      that researchers using MI should perform many more imputations than previously
      considered sufficient. These recommendations are based on gamma, and take into
      consideration one's tolerance for a preventable power falloff (compared to FIML)
      due to using too few imputations.

PMID- 17549636
TI  - Preventing homelessness: a consumer perspective.

PMID- 17549637
TI  - Closing a front door to homelessness among veterans.
AB  - The U.S. Department of Veterans Affairs (VA) has been identified as a mainstream
      institution to help prevent homelessness among America's veterans. The large
      numbers of incarcerated veterans with serious mental illnesses and substance
      abuse disorders who are at risk for homelessness support the need for expanded VA
      outreach to this population. Since 2002, the VA has contacted almost 6,500
      veterans in prison or jail. Its leadership role in affording comprehensive
      health, mental health, social resources, corrections outreach, and current policy
      and planning strategies positions the VA to provide system wide service to
      veterans leaving correctional institutions. As this VA outreach program proceeds,
      examining the links among program assumptions, veteran needs and outcomes, and
      existing evaluation processes can help to maintain focus on homelessness
      prevention strategies.

PMID- 17549638
TI  - Cognitive impairments and the prevention of homelessness: research and practice
      review.
AB  - Cognitive impairments can increase significantly a person's level of risk for
      becoming or remaining homeless. Five topics are explored that address these
      impairments in preventing homelessness: (1) the nature and estimated prevalence
      of cognitive impairments among people who are homeless, especially those with
      vulnerabilities like mental illness or substance abuse; (2) the multiple origins
      of these impairments; (3) how these impairments impact services for people at
      risk for homelessness; (4) good practice approaches to handling cognitive
      impairments in homeless shelters, supported housing programs, and other service
      systems for people at risk for homelessness; and, (5) important research and
      practice issues requiring further action.

PMID- 17549639
TI  - Alteration of mitochondrial function and cell sensitization to death.
AB  - Stimulation of cell death is a powerful instrument in the organism's struggle
      with cancer. Apoptosis represents one mode of cell death. However, in a variety
      of tumor cells proapoptotic mechanisms are downregulated, or not properly
      activated, whereas antiapoptotic mechanisms are upregulated. Mitochondria are
      known as key players in the regulation of apoptotic pathways. Specifically,
      permeabilization of the mitochondrial outer membrane and subsequent release of
      proapoptotic proteins from the intermembrane space are viewed as decisive events
      in the initiation and/or execution of apoptosis. Disruption of mitochondrial
      functions by anticancer drugs, which induce oxidative stress, inhibit
      mitochondrial respiration, or uncouple oxidative phosphorylation, can sensitize
      mitochondria in these cells and facilitate outer membrane permeabilization.

PMID- 17549640
TI  - Chemotherapy through mitochondrial apoptosis using nutritional supplements and
      herbs: a brief overview.
AB  - There has been increased interest in the use of naturally occurring compounds
      with chemopreventive and chemotherapeutic effects in the treatment of cancers.
      This review summarizes the most recent advances that provide new insights into
      the molecular mechanisms underlying the apoptotic potential of nutritional
      supplements and herbs. Apoptosis is an essential process in the pathogenesis of
      cancer and its mechanisms can be subdivided into either a death receptor
      dependent extrinsic pathway or an independent (mitochondrial or intrinsic)
      pathway. Nutritional supplements and herbs can exert their effects on such
      pathways separately, sequentially, or in a manner of "crosstalk" between
      pathways. A strong correlation between the early collapse of the mitochondrial
      membrane potential and apoptosis was found for most nutritional supplements and
      herbs that have been studied. These observations provide examples of the
      development of mitochondrial targeting strategies for cancer therapy.

PMID- 17549641
TI  - Arsenic trioxide and neuroblastoma cytotoxicity.
AB  - The majority of aggressive forms of the childhood tumor neuroblastoma can with
      current treatment protocols not be cured and possess a major challenge in
      pediatric oncology. After initial rounds of chemotherapy, surgery and
      irradiation, which in most cases result in tumor regression, these aggressive
      neuroblastomas relapse and frequently develop drug resistance. As approximately
      50% of the children with neuroblastoma have an aggressive form, there is a
      compelling demand for new treatment strategies. Arsenic trioxide has the capacity
      to kill multidrug-resistant neuro-blastoma cells in vitro and in vivo and the
      drug is currently being evaluated in clinical trials. In this report we discuss
      the background to the use of arsenic trioxide in cancer therapy and the currently
      known mechanisms by which arsenic trioxide kills human neuroblastoma cells.

PMID- 17549642
TI  - Mitochondria-mediated ATP depletion by anti-cancer agents of the jasmonate
      family.
AB  - Jasmonates are plant stress hormones that induce suppression of proliferation and
      death in cancer cells, while being selectively inactive towards non-transformed
      cells. Jasmonates can overcome apoptotic blocks and exert cytotoxic effects on
      drug-resistant cells expressing p53 mutations. Jasmonates induce a rapid
      depletion of ATP in cancer cells. Indeed, this steep drop occurs when no signs of
      cell death are detectable yet. Experiments using modulators of ATP synthesis via
      glycolysis or oxidative phosphorylation suggest that the latter is the pathway
      suppressed by jasmonates. Consequently, the direct effects of jasmonates on
      mitochondria were evaluated. Jasmonates induced cytochrome c release and swelling
      in mitochondria isolated from cancer cells but not from normal ones. Thus, the
      selectivity of jasmonates against cancer cells is rooted at the mitochondrial
      level, and probably exploits differences between mitochondria from normal versus
      cancer cells. These findings position jasmonates as promising anti-cancer drugs
      acting via energetic depletion in neoplastic cells.

PMID- 17549643
TI  - Apoptotic cellular events for selenium compounds involved in cancer prevention.
AB  - Converging data from epidemiological, ecological, and clinical studies have shown
      that selenium (Se) can decrease the risk for some types of human cancers.
      Induction of apoptosis is considered an important cellular event that can account
      for the cancer preventive effects of Se. Prior to occurrence of apoptosis, Se
      compounds alter the expression and/or activities of signaling molecules,
      mitochondria-associated factors, transcriptional factors, tumor suppressor genes,
      and cellular reduced glutathione. Mechanistic studies have demonstrated that the
      methylselenol metabolite pool has many desirable attributes of chemoprevention,
      whereas the hydrogen selenide pool with excess of selenoprotein synthesis can
      lead to DNA single-strand breaks. To elucidate the effects of Se on cytotoxic
      events, it should be remembered that the chemical forms and the dose of Se, and
      the experimental system used, are determinants of its biological activities. This
      mini-review focuses on elucidation of the molecular mechanisms of cancer
      prevention by Se with the apoptotic approach.

PMID- 17549644
TI  - Reaching and teaching preceptors: limited success from a multifaceted faculty
      development program.
AB  - We conducted a six-pronged preceptor faculty development program that included a
      listserve and interactive Web-based teaching scenarios. A total of 144 preceptors
      in a required preceptorship program were offered traditional continuing medical
      education (CME), a preceptor listserve, an electronic clinical teaching
      discussion group, an orientation videotape, a CD-ROM on teaching skills, and
      technology support. On Web-based evaluation, 31% of participants responded.
      Eighty percent of preceptors allowed us to subscribe them to the listserve, and
      most agreed it was useful. One third of preceptors responded to an electronic
      clinical teaching case discussion, most rating it useful to their precepting. The
      listserve and electronic teaching cases hold promise for preceptor faculty
      development.

PMID- 17549646
TI  - Getting the news from poetry.

PMID- 17549647
TI  - Faculty perceptions of the ACGME resident duty hour regulations in family
      medicine.
AB  - BACKGROUND AND OBJECTIVES: Accreditation Council for Graduate Medical Education
      (ACGME) duty hour regulations have significantly changed residency education.
      Initial research focused heavily on resident experiences, while changes in
      faculty roles and effects on patient care and resident education have received
      less attention. This survey examines faculty perceptions of the effect of duty
      hour changes in academic family medicine. METHODS: Family medicine faculty
      members from 15% of ACGME-accredited residencies were surveyed. The survey
      included demographic information and Likert-type questions about changes in
      faculty duties, patient care, resident education, and satisfaction with academic
      medicine. RESULTS: A total of 368 of 672 surveys were returned; 97% of the 69
      surveyed programs were represented. The average faculty workweek was 66 hours,
      including call. Of respondents, 81% felt that weekly faculty hours were unchanged
      since duty hours; 19% thought work hours had increased. Faculty felt that
      residency education and patient care were not positively affected by duty hours.
      Statistically significant differences were found between perceptions of faculty
      who did and did not deliver babies. Twenty percent of faculty members are
      considering leaving academic medicine in relation to duty hours. CONCLUSIONS:
      Consistent with research from other specialties, many faculty members perceive
      that their work roles have increased in certain areas. Resident performance and
      patient care are not seen to be improved as a result of duty hours. Further
      research into the unexpected findings involving labor and delivery
      responsibilities is needed.

PMID- 17549648
TI  - A descriptive analysis of abortion training in family medicine residency
      programs.
AB  - BACKGROUND AND OBJECTIVES: Access to abortion services in the United States is
      declining. While family physicians are well suited to provide this care, limited
      training in abortion occurs in family medicine residency programs. This study was
      designed to describe the structure of currently available training and the
      experience of residents participating in these programs. METHODS: E-mail
      questionnaires were sent to key faculty members and third-year residents in nine
      programs that have required abortion training. These faculty members and a sample
      of residents also completed semi-structured interviews. RESULTS: Residency
      programs varied in the amount of time dedicated to the procedural aspects of
      abortion training, ranging from 2 to 8 days, and also in non-procedural aspects
      of training such as values clarification and didactics. Themes that emerged from
      interviews with residents included the benefit of training with respect to
      technical skills and continuity of care. In addition, residents valued discussion
      of the emotional aspects of abortion care and issues relating to performing
      abortions after graduation from residency. CONCLUSIONS: While the details of the
      curricula vary, residents in programs with required abortion training generally
      felt positively about their experiences and felt that abortion was an appropriate
      procedure for family physicians to provide. Residents emphasized the importance
      of both non-procedural and technical aspects of training.

PMID- 17549649
TI  - Patient safety in after-hours telephone medicine.
AB  - OBJECTIVES: This study analyzed our family medicine department's after-hours
      telephone medicine systems at an academic health center from a patient safety
      perspective. The research questions were (1) What are the threats to patient
      safety associated with after-hours telephone medicine and (2) What kinds of
      errors are made during after-hours telephone medicine? METHODS: Subjects were
      patients at the University of Kentucky family medicine practice who called in to
      the after-hours answering service. Telephone interviews were conducted with 64
      patients over 10 weeks. During the interviews, patients described their telephone
      medicine experience, identified any problems, and reported potential or actual
      harm (patient-identified threats to patient safety). Two registered nurses and
      one physician analyzed the patient narratives to identify threats to patient
      safety (medical personnel-identified threats to patient safety). RESULTS: Sixty
      three analyzable patient interviews identified four instances (6%) of temporary
      physical harm. Two separate after-hours calls (3%) involved four medical errors
      with potentially serious consequences to patient safety (wrong dose, serious
      illness not ruled out). Fourteen calls (22%) involved events that could have
      threatened patient safety. CONCLUSIONS: Situations that threaten patient safety
      occur frequently in telephone medicine. Although this study is too small to draw
      strong conclusions, it suggests that there are risks to patient safety associated
      with after-hours telephone medicine.

PMID- 17549650
TI  - Research funding and mentoring in family medicine residencies.
AB  - BACKGROUND AND OBJECTIVES: This study's purpose was to measure the current status
      of research funding and mentoring in family medicine residencies and to ascertain
      what resources are needed to increase residencies' research output. METHODS: This
      was a cross-sectional survey of family medicine residency program directors in
      the United States. We measured grant funding sources, availability of mentors,
      the likelihood programs could qualify for National Institutes of Health (NIH) K
      awards, barriers to research, and how these factors varied by program type.
      RESULTS: The response rate was 66% (298/453). Medical school-based programs were
      much more likely to report that their family medicine faculty wrote funded
      research grants than were community-based medical school affiliated programs (76%
      versus 32%). The majority of both program types reported that research mentors
      were available (85% versus 60%). Very few programs of either type were likely to
      meet the minimum requirements for NIH K01, K08, or K23 awards (29% for medical
      school programs versus 3% for community programs). The most commonly reported
      specific resources needed to increase research output were time, money, and more
      faculty (range 86% to 92% between program types). CONCLUSIONS: The majority of
      family medicine residencies did not receive grant funding for research, reported
      that time and money were the most significant barriers to research, but were
      ineligible to receive support from NIH K awards. More realistic funding
      mechanisms are needed to support residency-based research faculty.

PMID- 17549651
TI  - PDA usage and training: targeting curriculum for residents and faculty.
AB  - BACKGROUND AND OBJECTIVES: Utilization of personal digital assistants (PDAs) in
      residency education is common, but information about their use and how residents
      are trained to use them is limited. Better understanding of resident and faculty
      PDA use and training is needed. METHODS: We used a cross-sectional survey of 598
      residents and faculty from the WWAMI (Washington, Wyoming, Alaska, Montana, and
      Idaho) Family Medicine Residency Network regarding PDA usage and training.
      RESULTS: Use of PDAs is common among residents (94%) and faculty (79%). Ninety
      six percent of faculty and residents report stable or increasing frequency of use
      over time. The common barriers to PDA use relate to lack of time, knowledge, and
      formal education. Approximately half of PDA users (52%) have received some formal
      training; however, the majority of users report being self-taught. Faculty and
      residents prefer either small-group or one-on-one settings with hands-on, self
      directed, interactive formats for PDA training. Large-group settings in lecture,
      written, or computer program formats were considered less helpful or desirable.
      CONCLUSIONS: PDAs have become a commonly used clinical tool. Lack of time and
      adequate training present a barrier to optimal application of PDAs in family
      medicine residency education.

PMID- 17549652
TI  - Defining the concept of primary care in South Korea using a Delphi method.
AB  - BACKGROUNDS AND OBJECTIVES: There is no consensus on the definition of primary
      care in South Korea. This study's objective was to define the concept of primary
      care using a Delphi method. METHODS: Three expert panels were formed, consisting
      of 16 primary care policy researchers, 45 stakeholders, and 16 primary care
      physicians. Three rounds of voting, using 9-point appropriateness scales, were
      conducted. The first round involved rating the appropriateness of 20 previously
      established attributes of primary care. In round 2, panelists received a summary
      of the first-round results and were asked to once again vote on the 10
      undetermined attributes and the provisional definition. The final round involved
      voting on the appropriateness of the revised definition. The Korean Language
      Society reviewed the revised definition. RESULTS: Four core (first-contact care,
      comprehensiveness, coordination, and longitudinality) and three ancillary
      (personalized care, family and community context, and community base) attributes
      were selected. The Korean definition of primary care was accomplished with all
      three panel groups arriving at a "very good" level of consensus. CONCLUSIONS: The
      Korean definition of primary care will provide a framework for evaluating
      performance of primary care in South Korea. It will also contribute to resolving
      confusion about the concept of primary care.

PMID- 17549653
TI  - Interpretation of absolute measures of disease risk in comparative research.
AB  - When comparing two groups, one receiving an experimental intervention and the
      other a placebo or nothing, researchers often wish to assess the disparity in
      risk of experiencing an event of interest, such as onset of disease. Relative
      risk, relative risk reduction, and odds ratio are often used to measure the
      association between potential benefit or harm and the intervention. However,
      these summary measures reflect relative disparities and are perhaps less useful
      in clinical practice than measures of absolute benefit or harm. We demonstrate
      that relative risk reduction is unaffected by the risk of an event in the control
      group and hence may either overestimate or underestimate the treatment effect.
      Absolute risk reduction accounts for the baseline control group event rate and is
      a more realistic quantification of treatment effect than relative measures.
      Number needed to treat (NNT) estimates the therapeutic effort needed to prevent
      one additional adverse event. NNT incorporates both relative risk reduction and
      the event rate without treatment. For a given relative risk reduction, we
      demonstrate the NNT will increase as the control event rate decreases. Thus, NNT
      has more-obvious implications for clinical decision making than risk estimates
      expressed in relative terms.

PMID- 17549654
TI  - Plagiarism in graduate medical education.
AB  - The act of overt plagiarism by graduates of accredited residency programs
      represents a failure in personal integrity. It also indicates a lack of
      professionalism, one of the six Accreditation Council for Graduate Medical
      Education (ACGME) competencies for graduate medical education. A recent
      experience at one geriatric fellowship indicates that the problem of plagiarism
      may be more prevalent than previously recognized. A situation was discovered at
      the geriatric medicine fellowship at Florida Hospital Family Medicine Residency
      Program in Orlando, Fla, in which three of the personal statements included in a
      total of 26 applications to the fellowship in the past 2 years contained portions
      plagiarized from a single Web site. The aim in documenting this plagiarism is to
      raise awareness among medical educators about the availability of online sources
      of content and ease of electronic plagiarism. Some students and residents may not
      recognize copying other resources verbatim as plagiarism. Residency programs
      should evaluate their own need for education about plagiarism and include this in
      the training of the competency of professionalism.

PMID- 17549657
TI  - Factors related to top running speed and economy.
AB  - The main purpose of the present study was to investigate the relationships
      between running mechanics, top running speed and economy in young endurance
      athletes. Twenty five endurance athletes (age 19.8 +/- 1.1 years, stature 1.82 +/
      0.07 m and body mass 69.4 +/- 7.5 kg) performed two separate tests on an indoor
      track. The first test was 8 x 30 m with increasing speed, and the second test was
      incremental 5 - 6 x 1,000 m. In the first test, ground reaction forces and stride
      characteristics were measured from each running speed. In the second test,
      running economy at the speed of 3.89 m . s (-1) and maximal oxygen uptake were
      determined. Ground contact time was the only factor which correlated
      significantly with both running economy (r = 0.49, p < 0.05) and maximal running
      speed (r = - 0.52, p < 0.01). Furthermore, maximal running speed was correlated
      significantly with the mass-specific horizontal force (r = 0.56, p < 0.01) but
      not with the vertical effective force. It is concluded that the short contact
      times required in economical and high speed running suggests that fast force
      production is important for both economical running and high top running speed in
      distance runners.

PMID- 17549658
TI  - Cardiac tissue Doppler in steroid users.
AB  - Anabolic steroids cause a variety of side effects, among them a slight concentric
      left ventricular hypertrophy. The objective of the present study was to clarify
      if they also induce alterations in left ventricular function. 14 male body
      builders with substantial intake of anabolic steroids (users) were examined by
      standard echocardiography and cardiac tissue Doppler imaging. They were compared
      to 11 steroid-free strength athletes (non-users) and 15 sedentary control
      subjects. Users showed an increased left ventricular muscle mass index. The ratio
      of peak transmitral blood flow velocities during early diastolic filling and
      atrial contraction did not differ between groups (users: 1.4 +/- 0.3; non-users:
      1.7 +/- 0.5; controls: 1.4 +/- 0.4). In contrast an analogous tissue Doppler
      parameter, the ratio of myocardial velocities during early and late ventricular
      filling in the basal septum, was significantly lower in users (1.2 +/- 0.4) when
      compared to non-users (1.6 +/- 0.5) or controls (1.6 +/- 0.6). The velocity
      gradient during myocardial E-wave in the posterior wall showed significantly
      lower values in users (3.8 +/- 1.3 1/s) as compared to controls (5.8 +/- 2.5
      1/s). There were no differences in systolic function. Summarizing strength
      athletes abusing anabolic steroids show negative alterations in diastolic
      function.

PMID- 17549659
TI  - Benefits of exercise training in Spanish prison inmates.
AB  - Prison populations are growing in Western countries. Imprisoned people usually
      have a poor health status and an increased risk to suffer chronic debilitating
      conditions as coinfection with the HIV and hepatitis C virus (HCV) and/or opioid
      dependency. We studied the effects of a 4-month concurrent cardiorespiratory and
      resistance training program on the cardiorespiratory fitness, lower and upper
      body dynamic strength endurance (6-RM test for bench press and knee-extensor
      exercise, respectively), muscle mass and quality of life (QOL) of adult prison
      inmates who are HIV/HVC co-infected and enrolled in a methadone maintenance
      program (n = 9; mean [SD] age: 37 [3] yrs). We also evaluated a control group (n
      = 10; 37 [2] yrs). A significant combined effect of group and time was found for
      peak completed workload (W) (p < 0.01), peak heart rate (HR (peak)) (p < 0.05)
      and rate of HR decrease at 1-min postexercise compared to HR (peak) (p < 0.05),
      respectively, in a gradual cycle ergometer test. A significant combined effect of
      group and time was also found for both bench press and knee-extensor 6-RM tests,
      respectively (p < 0.05). Supervised exercise training can improve the overall
      physical fitness of incarcerated people. Our results suggest that this type of
      intervention could be applied in prisons of Western societies.

PMID- 17549660
TI  - [Intravenous thrombolysis beyond the 3h time window after stroke onset and in
      stroke patients after 80 years and older].

PMID- 17549661
TI  - [Diagnosis and pharmacological treatment of multiple sclerosis].

PMID- 17549662
TI  - Frequency of visualization of presumed celiac ganglia by endoscopic ultrasound.
AB  - BACKGROUND AND STUDY AIMS: Celiac ganglia can be visualized by endoscopic
      ultrasound (EUS). It is unknown how often ganglia are visualized during EUS, and
      what clinical factors are associated with ganglion visualization. The aim of this
      study was to prospectively evaluate the frequency of visualization of presumed
      celiac ganglia by EUS and to identify factors that predict their visualization.
      PATIENTS AND METHODS: Clinical, demographic, EUS, and cytologic data were
      collected prospectively from 200 unselected patients who were undergoing EUS in a
      tertiary referral centre. When presumed celiac ganglia were visualized, their
      size, number, location, and echo features were noted. When presumed ganglia were
      aspirated, the results of cytology were recorded. RESULTS: The most common
      indication for EUS was investigation of a pancreatic mass or cyst (25 %).
      Presumed celiac ganglia were identified in 81 % of patients overall. Logistic
      regression analysis determined that female sex and having no prior history of
      gastrointestinal surgery were independently associated with ganglion
      visualization. Among patients whose ganglia were visualized, more ganglia were
      seen per patient with linear echo endoscopes (2, range 0 - 5) than with radial
      echo endoscopes (1, range 0 - 4) ( P = 0.001). Presumed celiac ganglia were
      aspirated in 10 patients; and cytologic examination revealed neural ganglia in
      all of these. CONCLUSIONS: Celiac ganglia can be visualized by EUS in most
      patients who undergo upper gastrointestinal EUS examinations, and are best seen
      with linear-array echo endoscopes. Ganglia can usually be differentiated from
      lymph nodes on the basis of their endosonographic appearance.

PMID- 17549663
TI  - Investigation of tissue inhibitor of metalloproteinases 1 in plasma from
      colorectal cancer patients and blood donors by surface-enhanced laser
      desorption/ionization time-of-flight mass spectrometry.
AB  - Early detection of colorectal cancer (CRC) improves patient survival. Plasma
      tissue inhibitor of metalloproteinases 1 (TIMP-1) measurements by enzyme-linked
      immunosorbent assay (ELISA) have been suggested as a new method for the early
      detection of CRC. To further investigate the nature of TIMP-1 in plasma, surface
      enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI TOF
      MS) was used. TIMP-1 measurements of plasma from 16 healthy donors and 14 CRC
      patients were performed using TIMP-1 monoclonal antibody in SELDI TOF MS and
      ELISA. SELDI TOF MS applying an antibody to TIMP-1 revealed that human plasma
      TIMP-1 has a mass of 25.1 kDa and exhibits several isoforms. Both methods showed
      increased plasma TIMP-1 values for cancer patients as compared to healthy
      individuals. The p values for the separation of the groups were 0.0019 for ELISA
      and <0.0001 for SELDI TOF MS. CRC did not fundamentally affect the appearance of
      TIMP-1 as evaluated by SELDI TOF MS.

PMID- 17549664
TI  - Levels of circulating cell-free serum DNA in benign and malignant breast lesions.
AB  - PURPOSES OF THE STUDY: We analyzed circulating cell-free DNA in the serum of
      patients with benign and malignant breast disease and in healthy individuals to
      determine its diagnostic value. BASIC PROCEDURES: Serum samples were obtained
      from 50 healthy individuals, 33 patients with malignant breast disease and 32
      patients with benign breast disease. Circulatory DNA was extracted from serum
      samples. Cell-free DNA was quantified by real-time quantitative PCR for the
      glyceraldehyde-3-phosphate dehydrogenase (GAPDH) gene. Tissue samples from
      patients with malignant and benign breast lesions were histopathologically
      examined. MAIN FINDINGS: The mean levels of circulating cell-free DNA in serum
      samples were 41,149 genome equivalents (GE)/mL in patients with malignant
      disease, 30,826 GE/mL in patients with benign disease, and 13,267 GE/mL in
      healthy individuals. Healthy individuals had significantly lower levels of cell
      free DNA than patients with malignant or benign breast disease (p=0.001,
      p=0.031). No significant difference was observed between malignant and benign
      disease. There was a correlation between cell-free DNA levels and tumor size but
      not with other tumor characteristics. PRINCIPAL CONCLUSION: Our results suggest
      that levels of circulating cell-free DNA in serum could have diagnostic value to
      discriminate between healthy individuals and patients with breast lesions but not
      between patients with malignant and benign breast lesions.

PMID- 17549665
TI  - Cytoplasmic localization of BAG-1 in leukoplakia and carcinoma of the tongue:
      correlation with p53 and c-erbB2 in carcinoma.
AB  - BACKGROUND: The present study evaluated the clinical significance of BAG-1, an
      antiapoptotic protein, in leukoplakia and carcinoma of the tongue. METHODS: BAG-1
      expression was evaluated by immunohistochemistry in paraffin-embedded tissues of
      leukoplakia (n=25) and carcinoma of the tongue (n=61). RESULTS: Cytoplasmic
      expression was predominantly seen in 80% and 70% of patients with leukoplakia and
      carcinoma, respectively. BAG-1 expression was found to be significantly lower in
      tobacco users than in non-tobacco users. BAG-1 expression in tobacco-using
      leukoplakia and carcinoma patients was compared by grouping the carcinoma
      patients according to lymph node status and disease stage. Carcinoma patients
      with tumor-positive lymph nodes had significantly lower BAG-1 expression than
      patients with negative lymph nodes and leukoplakia. Further, a trend towards an
      inverse correlation was observed with p53 and c-erbB2. In univariate and
      multivariate survival analysis, patient subgroups with 2+ or 3+ marker positivity
      (BAG-1 negativity, p53 and c-erbB2 positivity) had a reduced overall survival
      compared with patient subgroups with 1+ marker positivity or negativity.
      CONCLUSION: BAG-1 negativity in association with p53 and c-erbB2 positivity
      identified a subgroup of tongue cancer patients with an aggressive phenotype.
      Hence, an antiapoptotic protein, BAG-1, was found to be down-regulated in chewing
      tobacco-mediated tongue carcinogenesis.

PMID- 17549666
TI  - Usefulness of CDK5RAP3, CCNB2, and RAGE genes for the diagnosis of lung
      adenocarcinoma.
AB  - We used oligonucleotide microarrays with probe sets to 22,283 genes to analyze
      the gene expression profile of lung adenocarcinoma. Cancerous and noncancerous
      tissue samples were obtained from 23 patients with stage I or II lung cancer; 18
      tissue pairs and 5 cancerous tissues. A list of 2065 genes that differentiate
      between cancerous and noncancerous tissues was generated using Winsorized paired
      t-tests. We analyzed CDK5RAP3 and CCNB2, which are involved in cell cycle
      progression, and RAGE. The first 2 of these 3 genes proved to be overexpressed in
      tumor tissue, whereas the RAGE gene was suppressed in tumor tissue. When CDK5RAP3
      and CCNB2 were examined in individual patients we found that in cases where one
      of these genes was only slightly overexpressed the other was highly
      overexpressed. The combined expression of the 2 cell cycle genes was found to be
      statistically significant for differentiating between cancerous and noncancerous
      tissues. Inclusion of the data for the RAGE gene made the differentiation more
      powerful. The gene expression ratio gave a clear result: when CDK5RAP3 was
      expressed more than RAGE, the tissue was carcinomatous, and vice versa. We
      therefore conclude that these 3 genes may be used as a very reliable biomarker of
      lung adenocarcinoma.

PMID- 17549667
TI  - Basic helix-loop-helix transcription factor profiling of lung tumors shows
      aberrant expression of the proneural gene atonal homolog 1 (ATOH1, HATH1, MATH1)
      in neuroendocrine tumors.
AB  - Microarray-based expression profiling studies of lung adenocarcinomas have
      defined neuroendocrine subclasses with poor prognosis. As neuroendocrine
      development is regulated by members of the achaete-scute and atonal classes of
      basic helix-loop-helix (bHLH) transcription factors, we analyzed lung tumors for
      expression of these factors. Out of 13 bHLH genes tested, 4 genes, i.e., achaete
      scute complex-like 1 (ASCL1, HASH1, Mash1), atonal homolog 1 (ATOH1, HATH1,
      MATH1), NEUROD4 (ATH-3, Atoh3, MATH-3) and neurogenic differentiation factor 1
      (NEUROD1, NEUROD, BETA2), showed differential expression among lung tumors and
      absent or low expression in normal lung. As expected, tumors that have high
      levels of ASCL1 also express neuroendocrine markers, and we found that this is
      accompanied by increased levels of NEUROD1. In addition, we found ATOH1
      expression in 9 (16%) out of 56 analyzed adenocarcinomas and these tumors showed
      neuroendocrine features as shown by dopa decarboxylase mRNA expression and
      immunostaining for neuroendocrine markers. ATOH1 expression as well as NEUROD4
      was observed in small cell lung carcinoma (SCLC), a known neuroendocrine tumor.
      Since ATOH1 is not known to be involved in normal lung development, our results
      suggest that aberrant activation of ATOH1 leads to a neuroendocrine phenotype
      similar to what is observed for ASCL1 activation during normal neuroendocrine
      development and in lung malignancies. Our preliminary data indicate that patients
      with ATOH1-expressing adenocarcinomas might have a worse prognosis.

PMID- 17549668
TI  - Association of human papillomavirus type 16 E7 and HLA class I antigen expression
      in cervical premalignant and malignant lesions.
AB  - In the present experiment we studied the correlation between HPV16 infection and
      expression of HLA-I antigen in cervical premalignant and malignant lesions
      (cervicitis, CIN, cervical squamous carcinomas and adenocarcinoma samples). The
      HPV16 E7 DNA load and the expression of HLA-I antigen in the samples were
      measured by real-time fluorescence quantitative polymerase chain reaction (RFQ
      PCR) and immunohistochemical S-P staining, respectively. Our data indicate that
      HPV16 E7 load was highly and positively associated with the development of
      cervical lesions (Spearman's correlation coefficient r=0.848, p<0.001), the
      negative rate of HLA-I antigen was significantly distinguished among groups
      (p<0.001), and HPV16 E7 infection and downregulation of HLA-I antigen were highly
      correlated in cervical lesions (Pearson's correlation coefficient r=-0.487,
      p<0.001). HPV16 E7 may play an important role in the downregulation of HLA-I
      antigen in cervical lesions, which results in the immune escape of the virus and
      the occurrence, development, invasion and metastasis of cancer. Furthermore,
      quantitative PCR for HPV16 E7 may play an important role in the early detection
      of cervical diseases and in guiding future therapy toward prevention.

PMID- 17549669
TI  - Molecular alterations in oral carcinogenesis: significant risk predictors in
      malignant transformation and tumor progression.
AB  - In this study an attempt was made to establish the significance of a battery of
      molecular alterations and thereby identify risk predictors in oral
      carcinogenesis. For this purpose, EGFR, Stat3, H-ras, c-myc, p53, cyclin D1, p16,
      Rb, Ki-67 and Bcl-2 were localized immunohistochemically in normal mucosa (n=12),
      hyperplasia (n=35), dysplasia (n=25), early stage carcinoma (n=65) and advanced
      stage carcinoma (n=70). Deregulation occurred at an early stage and the number of
      alterations increased with disease progression. Using multivariate logistic
      regression analysis, the significant risk predictor for hyperplasia from normal
      mucosa was Ki-67 (OR=5.75, p=0.021); the significant risk predictors for
      dysplasia from hyperplasia were EGFR (OR=12.96, p=0.002), Stat3 (OR=17.16,
      p=0.0001), p16 (OR=5.50, p=0.039) and c-myc (OR=5.99, p=0.052); the significant
      risk predictors for early stage carcinoma from dysplasia were p53 (OR=6.63,
      p=0.0001) and Rb (OR=3.81, p=0.056); and the significant risk predictors for
      further progression were EGFR (OR=5.50, p=0.0001), Stat3 (OR=4.49, p=0.0001), H
      ras (OR=4.05, p=0.001) and c-myc (OR=2.99, p=0.015). Cyclin D1 holds a key
      position linking upstream signaling pathways to cell cycle regulation. Gene
      products of the mitogenic signaling pathway play an equally significant role as
      cell cycle regulatory proteins in the hyperplasia-dysplasia-early-advanced
      carcinoma sequence and together may provide a reference panel of markers for use
      in defining premalignant lesions and predicting the risk of malignant
      transformation and tumor progression.

PMID- 17549670
TI  - Involvement of NK cells against tumors and parasites.
AB  - Host resistance against pathogens depends on a complex interplay of innate and
      adaptive immune mechanisms. Acting as an early line of defence, the immune system
      includes activation of neutrophils, tissue macrophages, monocytes, dendritic
      cells, eosinophils and natural killer (NK) cells. NK cells are lymphoid cells
      that can be activated without previous stimulation and are therefore like
      macrophages in the first line of defence against tumor cells and a diverse range
      of pathogens. NK cells mediate significant activity and produce high levels of
      proinflammatory cytokines in response to infection. Their cytotoxicity production
      is induced principally by monocyte-, macrophage- and dendritic cell-derived
      cytokines, but their activation is also believed to be cytokine-mediated.
      Recognition of infection by NK cells is accomplished by numerous activating and
      inhibitory receptors on the NK cells' surface that selectively trigger the
      cytolytic activity in a major histocompability complex-independent manner. NK
      cells have trypanocidal activity of fibroblast cells and mediate direct
      destruction of extracellular epimastigote and trypomastigote forms of T. cruzi
      and T. lewisi in vitro; moreover, they kill plasmodia-infected erythrocytes
      directly through cell-cell interaction. This review provides a more detailed
      analysis of how NK cells recognize and respond to parasites and how they mediate
      cytotoxicity against tumor cells. Also the unique role of NK cells in innate
      immunity to infection and the relationship between parasites and carcinogenesis
      are discussed.

PMID- 17549671
TI  - Interchangeability and diagnostic accuracy of two assays for total and free
      prostate-specific antigen: two not always related items.
AB  - The variation between different PSA assays seems to influence the interpretation
      of individual PSA values and the clinical decisions about prostate cancer. One
      reason for this variability could be the different reactivity of antibodies for
      the various molecular forms of serum PSA; as a result, samples containing the
      same amount of tPSA but different proportions of fPSA can produce very different
      values. In this study, serum samples were collected prospectively from 152
      consecutive patients referred to 2 institutions (Regional Hospital, Venice, 90
      subjects; San Bortolo Hospital, Vicenza, 62 subjects) for PSA elevation and/or
      symptoms. Serum samples were assessed according to the manufacturers'
      instructions on the following 2 analyzers: the Immulite 2000 assay (Diagnostic
      Products Corporation, Los Angeles, USA), which measures tPSA and fPSA, and the
      ADVIA Centaur (Bayer Diagnostics, Tarrytown, USA), which assays tPSA and cPSA.
      cPSA values were transformed into fPSA by the equation fPSA=tPSA-cPSA. When
      taking Immulite tPSA and f/tPSA values as 100%, ADVIA Centaur values were 92.6%
      and 122%, respectively, which means that 20% of patients would be classified
      differently according to the traditional biopsy cutoff. In conclusion, there are
      considerable differences between the 2 methods, which could affect clinical
      decisions.

PMID- 17549672
TI  - Elevated plasma levels of the novel hormone INSL3 in a woman with metastatic
      ovarian cancer.

PMID- 17549673
TI  - HIV-associated Hodgkin's lymphoma. Antiapoptotic pathways and mechanisms for
      immune escape by tumor cells in the setting of improved immunity.

PMID- 17549674
TI  - Semiochemicals for biting fly control: their identification and exploitation.
AB  - Insects that feed on the blood of vertebrates are difficult to control, and many
      previous efforts have been unsuccessful. This is becoming an ever increasing
      issue, not only in developing countries, but also in developed countries, as
      exemplified by the recent spread of West Nile virus by mosquitoes across the USA
      and recent dengue outbreaks in Singapore and Australia. Investigating the ways in
      which biting insects interact with each other, their environment and their hosts
      is providing valuable knowledge that will lead to the development of improved
      control technologies. For instance, recent advances in chemical ecology research
      have led to the identification of new semiochemicals that show great potential as
      control agents against biting insects. Exciting new chemical ecology tools and
      control technologies for the future are discussed.

PMID- 17549675
TI  - Enantioselective resolution of thyroxine hormone by high-performance liquid
      chromatography utilizing a highly fluorescent chiral tagging reagent.
AB  - A highly fluorescent chiral tagging reagent, 4-(3-isothiocyanatopyrrolidin-1-yl)
      7-(N,N-dimethylaminosulfonyl-2,1,3-benzoxadiazole, [R(-)-DBD-PyNCS], was employed
      to develop an indirect resolution method for efficient separation of thyroxine
      enantiomers,D-T(4) and L-T(4). The reaction of R(-)-DBD-PyNCS with the thyroxine
      enantiomers proceeds effectively at 40 degrees C for 20 min in the presence of
      basic medium to produce the corresponding pair of diastereomers. No racemization
      occurs during the tagging reaction under the optimized conditions. Various
      experimental parameters for derivatization reaction including the species of
      catalyst, the concentration of tagging reagent and reaction temperatures, have
      been examined to get a highest yield for T(4) derivatives. The structure of T(4)
      derivatives was identified based on ESI-MS/MS measurements in negative mode. The
      efficient separation of D-, L-T(4) derivatives was achieved by isocratic elution
      with water-acetonitrile mobile phase containing 1% AcOH on a reversed phase
      column utilizing a conventional fluorescence detector. The resolution (Rs) value
      of the diastereomers derived from thyroxine was 5.1. The calibration curves of
      both the D-T(4) and L-T(4) were linear over the concentration range of 0.1-20
      microg/ml. The limits of detection (S/N = 3) for both D-T(4) and L-T(4) were 0.2
      ng per injection. The proposed method was applied to the determination of D-T(4)
      and L-T(4) in pharmaceutical formulations and human serum samples.

PMID- 17549676
TI  - Chromatography of amino acids and short peptides. New advances.
AB  - The newest results in the application of various chromatographic methods (gas
      liquid chromatography, liquid chromatographic techniques, electrically driven
      systems) for the separation and quantitative determination of amino acids and
      short peptides in pure state and in complicated matrices are compiled. The
      results are concisely described and critically evaluated. The future trends of
      the chromatographic analysis of amino acids and short peptides are briefly
      discussed.

PMID- 17549677
TI  - A rapid and simple high-performance liquid chromatography method for the
      determination of human plasma levofloxacin concentration and its application to
      bioequivalence studies.
AB  - A high-performance liquid chromatography method with fluorescence detection (HPLC
      FLD) for the determination of levofloxacin in human plasma is described.
      Neutralized with phosphate buffer (pH 7.0), the sample (0.1 mL) was extracted
      with dichlormethane (1 mL). After voltex-mixing and centrifuged at 3000g for 6
      min at 4 degrees C, the upper aqueous layer was aspirated using a micro vacuum
      pump and the organic layer was directly transferred to a clean test tube without
      pipetting. The organic solvent was evaporated and the residues were reconstituted
      with the mobile phase. Levofloxacin and terazosin (internal standard, IS) were
      chromatographically separated on a C(18) column with a mobile phase containing
      phosphate buffer (pH 3.0, 10 mm), acetonitrile and triethylamine (76:24:0.076,
      v/v/v) at a flow rate of 1 mL/min. The analytes were detected using fluorescence
      detection at an excitation and emission wavelength of 295 and 440 nm,
      respectively. The linear range of the calibration curves was 0.0521-5.213
      microg/mL for levofloxacin with a lower limit of quantitation (0.0521 microg/mL).
      The retention times of levofloxacin and terazosin were 2.5 and 3.1 min,
      respectively. Within- and between-run precision was less than 12 and 11%,
      respectively. Accuracy ranged from -6.3 to 4.5%. The recovery ranged from 86 to
      89% at the concentrations of 0.0521, 0.5213 and 5.213 microg/mL. The present HPLC
      FLD method is sensitive, efficient and reliable. The method described herein has
      been successfully used for the pharmacokinetic and bioequivalence studies of a
      levofloxacin formulation product after oral administration to healthy Chinese
      volunteers.

PMID- 17549678
TI  - Highly sensitive and quantitative analysis of polyeptides using a new gradient
      system based on an abrupt change in adsorption of polypeptide to the reversed
      phase column packing.
AB  - During a study of 100 microL aliquots of urocortin containing various
      acetonitrile contents, we hypothesized that a change in the acetonitrile content
      in the solution across a specific content of acetonitrile (critical threshold)
      causes an abrupt change in adsorption capacity to the column packing. Circular
      dichroism measurements suggest that the conformational change induced by
      acetonitrile in the solution causes the abrupt change in adsorption capacity, and
      this solvent-induced conformational change is reversible across the critical
      threshold. This hypothesis can apply to various polypeptides with molecular
      weights range from 1007 to 6789 and to other organic solvents. A new gradient
      system utilizing the instant recovery of the adsorption capacity across the
      critical threshold was designed, and applied to the analysis of a 100 microL
      aliquot of various polypeptide solutions. The results suggest that use of a
      solution containing organic solvents more than the critical threshold allows
      successful dilution of polypeptides up to picomolar concentration range without
      any loss due to its adsorption during handling procedures and loading onto the LC
      system, and that a new gradient system enables quantitative analysis of
      polypeptides at picomolar concentrations in such solutions.

PMID- 17549679
TI  - HPLC method for comparative study on tissue distribution in rat after oral
      administration of salvianolic acid B and phenolic acids from Salvia miltiorrhiza.
AB  - A sensitive and selective high-performance liquid chromatography method was
      developed and validated to determine the prototype of salvianolic acid B and the
      metabolites of phenolic acids (protocatechuic acid, vanillic acid and ferulic
      acid) in rat tissues after oral administration of total phenolic acids and
      salvianolic acid B extracted from the roots of Salvia miltiorrhiza, respectively.
      The tissue samples were treated with a simple liquid-liquid extraction prior to
      HPLC. Analysis of the extract was performed on a reverse-phase C(18) column with
      a mobile phase consisting of acetonitrile and 0.05% trifluoracetic acid. The
      calibration curves for the four phenolic acids were linear in the given
      concentration ranges. The intra-day and inter-day relative standard deviations in
      the measurement of quality control samples were less than 10% and the accuracies
      were in the range of 88-115%. The average recoveries of all the tissues ranged
      from 78.0 to 111.8%. This method was successfully applied to evaluate the
      distribution of the four phenolic acids in rat tissues after oral administration
      of total phenolic acids of Salvia miltiorrhiza or salvianolic acid B and the
      possible metabolic pathway was illustrated.

PMID- 17549680
TI  - Localization of annexin II in the paranodal regions and Schmidt-Lanterman
      incisures in the peripheral nervous system.
AB  - Annexin II (AX II) is a member of the family of calcium-dependent actin- and
      phospholipid-binding proteins implicated in numerous intracellular functions such
      as signal transduction, membrane trafficking, and mRNA transport, as well as in
      the regulation of membrane/cytoskeleton contacts and extracellular functions. AX
      II is expressed in the central nervous system (CNS) and is upregulated in some
      pathological conditions. However, expression and localization of this protein in
      the peripheral nervous system (PNS) is still uncertain. In the present study, we
      examined the expression and distribution of AX II in the PNS. By western blot
      analysis, we found that a higher level of AX II was present in sciatic nerve
      homogenates than in brain homogenates. RT-PCR of total RNA from rat sciatic
      nerves revealed that AX II was synthesized within the nerves. Immunohistological
      analysis showed the characteristic distribution of AX II in Schmidt-Lanterman
      incisures (SLI) as well as in the paranodal regions. Localization of AX II in the
      PNS was examined in two mutant mouse models, shiverer and cerebroside
      sulfotransferase knockout mice, both of which show increased numbers of SLI. The
      paranodal axo-glial junction is also disrupted in the latter. Interestingly, the
      staining intensities of AX II in these regions were increased markedly in both
      mutants, suggesting that not only the numbers but also AX II content in each
      incisure and paranodal loop were affected. From its characteristic distribution
      and molecular features, AX II may be important for myelin function in the PNS.

PMID- 17549681
TI  - Risk assessment of renal cell carcinoma using alkaline comet assay.
AB  - BACKGROUND: DNA damage induced by mutagens has been associated with an
      individual's susceptibility to cancer. METHODS: In the current study, which
      involved 193 renal cell carcinoma (RCC) patients and 193 controls, DNA damage
      before mutagen induction (baseline), after benzo(alpha)pyrene dio epoxide (BPDE)
      treatment, and after gamma-radiation induction were assayed by comet assay in
      peripheral blood lymphocytes. Olive tail moments were used as DNA damage
      parameters. The 5 variables that were analyzed for their associations with RCC
      risk were baseline, BPDE-induced, gamma-radiation-induced, net BPDE-induced (BPDE
      induced subtract baseline), and net gamma-radiation-induced (gamma-radiation
      induced subtract baseline) Olive tail moments. RESULTS: Significantly higher
      Olive tail moments were observed in cases compared with controls at baseline
      (1.95 vs 1.65; P = .008), after BPDE induction (3.10 vs 2.38; P < .001), and
      after gamma-radiation induction (4.25 vs 3.47; P < .001). The net BPDE-induced
      and gamma-radiation-induced DNA damage was also found to be significantly higher
      in cases compared with controls (P < .001 for both mutagens). Using the 75th
      percentile Olive tail moments in the controls as the cutoff point, the authors
      found that high levels of baseline DNA damage, BPDE-induced DNA damage, and gamma
      radiation-induced DNA damage were associated with significantly increased risks
      of RCC, with odds ratios of 1.96 (95% confidence interval [95% CI], 1.26-3.06),
      2.70 (95% CI, 1.72-4.23), and 3.13 (95% CI, 1.99-4.92), respectively. Similarly,
      net BPDE-induced and net gamma-radiation-induced DNA damages were also found to
      be significantly associated with elevated risks of RCC. CONCLUSIONS: The results
      of the current study suggest that both baseline and mutagen-induced DNA damages
      assessed by comet assay are associated with an increased risk of RCC.

PMID- 17549682
TI  - Expression and function of water channels (aquaporins) in migrating malignant
      astrocytes.
AB  - Aquaporins (AQP) constitute the principal pathway for water movement across
      biological membranes. Consequently, their expression and function is important
      for cell volume regulation. Glioma cells quickly adjust their cell volume in
      response to osmotic challenges or spontaneously as they invade into the narrow
      and tortuous extracellular spaces of the brain. These cell volume changes are
      likely to engage water movements across the cell membrane through AQP. AQP
      expression in glioma cells is poorly understood. In this study, we examined the
      expression of AQP in several commonly used human glioma cell lines (D54, D65,
      STTG1, U87, U251) and in numerous acute patient biopsies by PCR, Western blot,
      and immunocytochemistry and compared them to nonmalignant astrocytes and normal
      brain. All glioma patient biopsies expressed AQP1, AQP4 and some expressed AQP5.
      However, when isolated and grown as cell lines they lose all AQP proteins except
      a few cell lines that maintain expression of AQP1 (D65, U251, GBM62).
      Reintroducing either AQP1 or AQP4 stably into glioma cell lines allowed us to
      show that each AQP is sufficient to restore water permeability. Yet, only the
      presence of AQP1, but not AQP4, enhanced cell growth and migration, typical
      properties of gliomas, while AQP4 enhanced cell adhesion suggesting differential
      biological roles for AQP1 and AQP4 in glioma cell biology.

PMID- 17549683
TI  - TGF-beta1/SMAD signaling induces astrocyte fate commitment in vitro: implications
      for radial glia development.
AB  - Radial glial (RG) cells are specialized type of cell, which functions as neuronal
      precursors and scaffolding guides to migrating neurons during cerebral cortex
      development. After neurogenesis and migration are completed, most of RG cells
      transform into astrocytes. Mechanism and molecules involved in this process are
      not completely elucidated. We previously demonstrated that neurons activate the
      promoter of the astrocyte maturation marker GFAP in astrocytes by secretion of
      transforming growth factor beta 1 (TGF-beta1) in vitro. Here, we studied the role
      of neurons and TGF-beta1 pathway in RG differentiation. To address this question,
      we employed cortical progenitor cultures enriched in GLAST/nestin double-labeled
      cells, markers of RG cells. TGF-beta1 and conditioned medium derived from neuron
      astrocyte cocultures (CM) decreased the number of cells expressing the precursor
      marker nestin and increased that expressing GFAP in cortical progenitor cultures.
      These events were impaired by addition of neutralizing antibodies against TGF
      beta1. Increase in the number of GFAP positive cells was associated with Smads
      2/3 nuclear translocation, a hallmark of TGF-beta1 pathway activation. PCR-assays
      revealed a decrease in the levels of mRNA for the RG marker, BLBP (brain lipid
      binding protein), due to TGF-beta1 and CM treatment. We further identified TGF
      beta1 receptor in cortical progenitor cultures suggesting that these cells might
      be target for TGF-beta1 during development. Our work provides strong evidence
      that TGF-beta1 might be a novel factor involved in RG-astrocyte transformation
      and highlights the role of neuron-glia interaction in this process.

PMID- 17549685
TI  - Hepatitis B vaccine and risk of multiple sclerosis.

PMID- 17549687
TI  - Catalytic activation through metal enolization of nucleophile precursors and
      synthetic applications to enantioselective Michael additions.
AB  - Catalytic activation methods of nucleophile precursors recently developed in our
      research group were reviewed in this paper. These include (i) the catalytic
      double activation method of nucleophile precursors through enol formation and of
      electrophiles through coordination in alcohols; (ii) the double catalytic
      activation method by use of both catalytic amounts of chiral Lewis acid and
      external achiral amine; (iii) the catalytic activation method of nucleophile
      precursors with a chiral cationic Lewis acid in the presence of molecular sieves;
      and (iv) the single catalytic activation of nucleophile precursors through metal
      enolization in alcohol media.

PMID- 17549688
TI  - Bis(oxazolinyl)phenyl transition metal complexes: synthesis, asymmetric
      catalysis, and coordination chemistry.
AB  - Molecular catalysts for organic synthesis should be constructed to be tailored to
      target reactions and their desirable conditions. In our search for them, we have
      studied new types of transition metal molecular catalysts dressed with a
      tridentate N,C,N modular ligand, which consists of a C2-symmetric side-by-side
      phenyl group with chiral bis(oxazolinyl) substituents. The ligand, 2,6
      bis(oxazolinyl)phenyl abbreviated as Phebox, can connect covalently to transition
      metals by the central carbon atom. Here, we review our recent work on the
      chemistry of Phebox and its metal complexes, including preparation, structural
      analysis, asymmetric Lewis acid catalysis, asymmetric hydrosilylation, asymmetric
      conjugate reduction, asymmetric reductive aldol reaction, and organometallic
      reactions.

PMID- 17549689
TI  - Development of efficient Lewis acid catalysts for intramolecular cycloaddition
      reactions of ester-tethered substrates.
AB  - We have developed novel bidentate Lewis acids that efficiently promote the
      intramolecular cycloaddition reactions of ester-tethered substrates. Bis
      aluminated triflic amide derivatives [TfN(AlR(1)R(2))2], which are generated by
      simply mixing triflic amide and 2 equiv of methyl aluminum or aluminum hydride,
      catalyzed intramolecular Diels-Alder (DA) reactions of ester-tethered 1,7,9
      trienes and intermolecular DA reactions of alpha,beta-unsaturated lactones. We
      also found that bimetallic Lewis acid derived from 1,1'-biphenyl-2,2'
      di(triflyl)amide and dimethylaluminum chloride promoted the intramolecular [3 +
      2] cycloaddition reaction of acrylate derivatives having an allylsilane part.

PMID- 17549690
TI  - Randomized controlled trials of treatments for hematologic malignancies: study
      characteristics and outcomes.
AB  - BACKGROUND: Although randomized controlled trials (RCTs) require a great deal of
      time, money, and effort, the majority of them have resulted in failure to verify
      a priori hypotheses. Therefore, the intention in the current study was to clarify
      the differential elements of studies with 'positive' and 'negative' outcomes.
      METHODS: The authors performed a comprehensive search of RCT reports on
      treatments for hematologic malignancies published between 1995 and 2004, with 264
      reports eventually identified. The expected rate and the observed rate for the
      primary endpoint were compared for 70 studies with all relevant information
      available. RESULTS: Of all the superiority trials (n = 256), positive studies
      accounted for 33%. Most of the major study characteristics were not found to be
      associated with the study outcome except for the primary endpoint. Studies
      evaluating event-free survival were more likely to report positive results than
      were those evaluating overall survival (P = .061). For the experimental treatment
      arm, the mean difference between the expected and observed rates was -10.1%
      (standard deviation [SD], 10.1%) in the negative studies, which indicates a rate
      lower than expected, and was 1.3% (SD, 9.2%) in the positive studies (P < .0001).
      In contrast, no statistical significance was observed for the standard treatment
      arm because the mean difference was 6.3% (SD, 10.7%) for the negative studies and
      3.0% (SD, 9.0%) for the positive studies (P = .1885). The journal impact factor
      was statistically significantly higher for the positive than for the negative
      reports (P < .0001). CONCLUSIONS: Giving adequate consideration to the estimated
      effect of an experimental therapy may be critical when planning an RCT.

PMID- 17549691
TI  - Primary Gleason pattern does not impact survival after permanent interstitial
      brachytherapy for Gleason score 7 prostate cancer.
AB  - BACKGROUND: The impact of primary Gleason pattern was determined on cause
      specific (CSS), biochemical progression-free (bPFS), and overall survival (OS)
      after brachytherapy for Gleason score 7 prostate cancer. METHODS: From April 1995
      to October 2003, 530 patients underwent brachytherapy for Gleason score 3+4 (n =
      300) or Gleason 4+3 (n = 230) prostate cancer. All patients underwent
      brachytherapy more than 3 years before analysis. The median follow-up was 5.7
      years. Of the 530 patients, 412 (77.7%) received supplemental external beam
      radiation therapy (XRT) and 177 (33.4%) received androgen deprivation therapy.
      bPFS was defined by a prostate-specific antigen (PSA) </=0.40 ng/mL after nadir.
      Multiple parameters were evaluated as predictors of CSS, bPFS, and OS. RESULTS:
      At 10 years, Gleason 3+4 versus 4+3 did not predict for CSS (96.7% vs 93.3%, P =
      .506), bPFS (97.0% vs 92.9%, P = .085), or OS (77.0% vs 78.0%, P = .933). Cox
      linear regression analysis demonstrated that clinical stage and radiation dose
      (D90) predicted for CSS, whereas pretreatment PSA, clinical stage, and prostate
      size predicted for bPFS. Patient age, diabetes, and tobacco were the strongest
      predictors for OS. To date, 57 patients have died, with 80.7% due to
      cardiovascular/pulmonary events or secondary malignancies. Five patients have
      died of prostate cancer. CONCLUSIONS: The primary Gleason pattern did not impact
      CSS, bPFS, or OS in Gleason score 7 prostate cancer. Deaths from
      cardiovascular/pulmonary disease and second malignancies were 9.6 times more
      common than death from prostate cancer.

PMID- 17549692
TI  - Bone health in children and adolescents after allogeneic stem cell
      transplantation: high prevalence of vertebral compression fractures.
AB  - BACKGROUND: This cross-sectional study evaluated the overall bone health and the
      prevalence of vertebral complications after stem cell transplantation (SCT) in
      prepubertal children and adolescents. METHODS: A total of 44 children and
      adolescents (median age, 10 years) were evaluated at a median of 3.8 years after
      SCT for areal bone mineral density (aBMD) with dual-energy X-ray absoptiometry
      and for vertebral fractures with instant vertebral assessment. Pretransplant and
      posttransplant medications and nutritional parameters were recorded, and plasma
      levels of vitamin D, calcium, phosphate, and parathormone were measured. RESULTS:
      Of the 44 patients, 16 (36%) had a BMD Z-score of <-1.0. The patients with low
      BMD did not differ from the others with regard to their clinical or biochemical
      characteristics. Prepubertal patients had better BMD Z-scores at all sites
      compared with pubertal or postpubertal subjects. This was evident especially at
      the hip, in which the median aBMD Z-score in prepubertal patients (-0.2; range, 
      0.5 to +1.7) was found to be significantly higher than in pubertal (-1.1; range, 
      1.5 to +0.4) and postpubertal (-1.1; range, -2.6 to +0.5) patients (P = .03).
      Five patients (11%) had a history of peripheral fractures. Nine patients (20%)
      had vertebral compression fractures, which were asymptomatic in 7 patients.
      CONCLUSIONS: Approximately one-third of patients who had undergone allogeneic SCT
      in childhood were found to have a reduced BMD before reaching adulthood. This was
      due in part to inadequate BMD gain during the pubertal years. The high prevalence
      of asymptomatic vertebral compression fractures calls for the systematic
      assessment of spinal health during the posttransplantation follow-up.

PMID- 17549693
TI  - Sequence specificity of inter- and intramolecular G-quadruplex formation by human
      telomeric DNA.
AB  - Human telomeric DNA consists of tandem repeats of the sequence 5'-d(TTAGGG)-3'.
      Guanine-rich DNA, such as that seen at telomeres, forms G-quadruplex secondary
      structures. Alternative forms of G-quadruplex structures can have differential
      effects on activities involved in telomere maintenance. With this in mind, we
      analyzed the effect of sequence and length of human telomeric DNA on G-quadruplex
      structures by native polyacrylamide gel electrophoresis and circular dichroism.
      Telomeric oligonucleotides shorter than four, 5'-d(TTAGGG)-3' repeats formed
      intermolecular G-quadruplexes. However, longer telomeric repeats formed
      intramolecular structures. Altering the 5'-d(TTAGGG)-3' to 5'-d(TTAGAG)-3' in any
      one of the repeats of 5'-d(TTAGGG)(4)-3' converted an intramolecular structure to
      intermolecular G-quadruplexes with varying degrees of parallel or anti-parallel
      stranded character, depending on the length of incubation time and DNA sequence.
      These structures were most abundant in K(+)-containing buffers. Higher-order
      structures that exhibited ladders on polyacrylamide gels were observed only for
      oligonucleotides with the first telomeric repeat altered. Altering the sequence
      of 5'-d(TTAGGG)(8)-3' did not result in the substantial formation of
      intermolecular structures even when the oligonucleotide lacked four consecutive
      telomeric repeats. However, many of these intramolecular structures shared common
      features with intermolecular structures formed by the shorter oligonucleotides.
      The wide variability in structure formed by human telomeric sequence suggests
      that telomeric DNA structure can be easily modulated by proteins, oxidative
      damage, or point mutations resulting in conversion from one form of G-quadruplex
      to another.

PMID- 17549694
TI  - Impact of self-assembly composition on the alternate interfacial electron
      transfer for electrostatically immobilized cytochrome c.
AB  - We report on the effects of self-assembled monolayer (SAM) dilution and thickness
      on the electron transfer (ET) event for cytochrome c (CytC) electrostatically
      immobilized on carboxyl terminated groups. We observed biphasic kinetic behavior
      for a logarithmic dependence of the rate constant on the SAM carbon number (ET
      distance) within the series of mixed SAMs of C(5)COOH/C(2)OH, C(10)COOH/C(6)OH,
      and C(15)COOH/C(11)OH that is in overall similar to that found earlier for the
      undiluted SAM assemblies. However, in the case of C(15)COOH/C(11)OH and
      C(10)COOH/C(6)OH mixed SAMs a notable increase of the ET standard rate constant
      was observed, in comparison with the corresponding unicomponent (omega-COOH)
      SAMs. In the case of the C(5)COOH/C(2)OH composite SAM a decrease of the rate
      constant versus the unicomponent analogue was observed. The value of the
      reorganization free energy deduced through the Marcus-like data analysis did not
      change throughout the series; this fact along with the other observations
      indicates uncomplicated rate-determining unimolecular ET in all cases. Our
      results are consistent with a model that considers a changeover between the
      alternate, tunneling and adiabatic intrinsic ET mechanisms. The physical
      mechanism behind the observed fine kinetic effects in terms of the protein
      rigidifying omega-COOH/CytC interactions arising in the case of mixed SAMs are
      also discussed.

PMID- 17549695
TI  - In vivo corrosion behavior of Mg-Mn-Zn alloy for bone implant application.
AB  - Magnesium alloy has been implanted in rats to investigate the in vivo degradation
      behavior of magnesium for bone implant application. After 9 weeks postoperation,
      100% implants were fixed and no inflammation was observed. Histological analysis
      showed new bone was formed around magnesium implant and no difference was found
      in the histological microstructure of the new bone and the cortical bone. A
      degradation or reaction layer, which was mainly composed of Ca, P, O, and Mg, was
      formed on the surface of magnesium alloy implants. High Ca content in the
      degradation layer displayed that magnesium could promote the deposition of Ca.
      Residual area calculation has showed that 10-17% magnesium alloy implant has been
      degraded in vivo. Compared with that of the controlled rats, no increase in serum
      magnesium and no disorder of kidney were observed after 15 weeks postoperation.
      After 18 weeks postoperation, 100% magnesium implants were fixed and no
      inflammation was observed. About 54% magnesium implant has degraded in vivo.
      Element analysis showed that Zn and Mn in Mg-Mn-Zn alloy distributed
      homogeneously in the residual magnesium implant, the degradation layer, and the
      surrounding bone tissue after 18 weeks implantation, indicating that Zn and Mn
      elements were easily absorbed by bioenvironment.

PMID- 17549696
TI  - Fasciola gigantica cathepsin L proteinase-based synthetic peptide for
      immunodiagnosis and prevention of sheep fasciolosis.
AB  - Sheep fasciolosis is a devastating burden for the livestock industry. We herein
      report on immunodiagnosis of fasciolosis, and significant protection of sheep
      against challenge infection with Fasciola gigantica following immunization with a
      peptide based on the H-Asp(110)-Lys-Ile-Asp-Trp-Arg-Glu-Ser-Gly-Tyr-Val-Thr-Glu
      Val(123)-OH (Fas14p) sequence of F. gigantica cathepsin L-cysteine proteinase.
      This sequence was synthesized in three different forms: as N(alpha) acetylated
      (Ac-Asp(110)-Lys-Ile-Asp-Trp-Arg-Glu-Ser-Gly-Tyr-Val-Thr-Glu-Val(123)-OH,
      FasAc14p), bearing at the amino-terminus an N(alpha) acetylated cystein (Ac-Cys
      Asp(110)-Lys-Ile-Asp-Trp-Arg-Glu-Ser-Gly-Tyr-Val-Thr-Glu-Val(123)-OH,
      FasAcCys14p), and conjugated to sequential oligopeptide carrier Ac-[Lys-Aib
      Gly](4)-OH (Ac-SOC(4)) through an amide bond formed between Val(123) carboxylic
      group of the epitope and the lysine N(epsilon) groups of the carrier (Ac
      [Lys(Fas14p)-Aib-Gly](4)-OH). Ac-[Lys(Fas14p)-Aib-Gly](4)-OH failed to readily
      discriminate between naive and infected sheep. In contrast, the free peptides
      reproducibly differentiated between parasite-free sheep, sheep infected with
      parasites other than Fasciola, and experimentally Fasciola-infected sheep. The
      data together indicated that the peptides might be of considerable use for
      discriminating between early and late, and low and high burden, sheep infection
      with F. gigantica. FasAc14p was chosen to determine whether a peptide based on a
      critical enzymatic site of cathepsin L proteinase may induce protection against
      challenge infection. Sheep immunization with FasAc14p peptide induced significant
      expression of interleukin-4 mRNA, and humoral antibodies that bound to
      molecule(s) on the intact surface membrane of newly excysted juvenile worms, and
      mediated their attrition. The immune responses were associated with significant
      (P < 0.02) decrease of 23.1% in worm recovery, but with no decrease in the size
      or maturation of worms recovered.

PMID- 17549697
TI  - Differential effects of anoxia on heart rate in developmental stages of the
      annual killifish Austrofundulus limnaeus that differ in their tolerance of
      anoxia.
AB  - Embryos of the annual killifish Austrofundulus limnaeus can experience oxygen
      deprivation as part of their normal developmental environment. We exposed embryos
      to anoxia and monitored heart activity for 48 hr, and subsequent aerobic recovery
      from anoxia for 40 hr. Embryos were tested at four different developmental stages
      that differ in their tolerance of anoxia. Our results indicate that high
      tolerance of anoxia is associated with an arrest of heart contractility during
      the first 24 hr of anoxia. These embryos recover to normoxic levels of heart rate
      within 16 hr of aerobic recovery. In contrast, embryos from later developmental
      stages that have a highly reduced ability to survive long-term anoxia experience
      a severe bradycardia but not an arrest of heart rate. These data illustrate a new
      and potentially powerful model for investigating the effects of anoxia on the
      developing cardiovascular system in vertebrates.

PMID- 17549698
TI  - LRRC4 inhibits human glioblastoma cells proliferation, invasion, and proMMP-2
      activation by reducing SDF-1 alpha/CXCR4-mediated ERK1/2 and Akt signaling
      pathways.
AB  - Gliomas take a number of different genetic routes in the progression to
      glioblastoma multiforme, a highly invasive variant that is mostly unresponsive to
      current therapies. The alpha-chemokine stromal cell-derived factor (SDF)-1 alpha
      binds to the seven transmembrane G-protein-coupled CXCR-4 receptor and acts to
      modulate cell migration and proliferation by activating multiple signal
      transduction pathways. Leucine-rich repeats containing 4 (LRRC4), a putative
      glioma suppressive gene, inhibits glioblastoma cells tumorigenesis in vivo and
      cell proliferation and invasion in vitro. We also previously demonstrated that
      LRRC4 controlled glioblastoma cells proliferation by ERK/AKT/NF-kappa B signaling
      pathway. In the present study, we demonstrate that CXC chemokine receptor 4
      (CXCR4) is expressed in human glioblastoma U251 cell line, and that SDF-1 alpha
      increases the proliferation, chemotaxis, and invasion in CXCR4+ glioblastoma U251
      cells through the activation of ERK1/2 and Akt. The reintroduction of LRRC4 in
      U251 cells inhibits the expression of CXCR4 and SDF-1 alpha/CXCR4 axis-mediated
      downstream intracellular pathways such as ERK1/2 and Akt leading to proliferate,
      chemotactic and invasive effects. Furthermore, we provide evidence for proMMP-2
      activation involvement in the SDF-1 alpha/CXCR4 axis-mediated signaling pathway.
      LRRC4 significantly inhibits proMMP-2 activation by SDF-1 alpha/CXCR4 axis
      mediated ERK1/2 and Akt signaling pathway. Collectively, these results suggest a
      possible important "cross-talk" between LRRC4 and SDF-1 alpha/CXCR4 axis-mediated
      intracellular pathways that can link signals of cell proliferation, chemotaxis
      and invasion in glioblastoma, and may represent a new target for development of
      new therapeutic strategies in glioma.

PMID- 17549699
TI  - Expression of tumor suppressor p53 facilitates DNA repair but not UV-induced G2/M
      arrest or apoptosis in Chinese hamster ovary CHO-K1 cells.
AB  - Tumor suppressor p53 is an essential regulator in mammalian cellular responses to
      DNA damage including cell cycle arrest and apoptosis. Our study with Chinese
      hamster ovary CHO-K1 cells indicates that when p53 expression and its
      transactivation capacity was inhibited by siRNA, UVC-induced G2/M arrest or
      apoptosis were unaffected as revealed by flow cyotmetric analyses and other
      measurements. However, inhibition of p53 rendered the cells slower to repair UV
      induced damages upon a plasmid as shown in host cell reactivation assay.
      Furthermore, the nuclear extract (NE) of p53 siRNA-treated cells was inactive to
      excise the UV-induced DNA adducts as analyzed by comet assay. Consistently, the
      immunodepletion of p53 also deprived the excision activity of the NE in the
      similar experiment. Thus, tumor suppressor p53 of CHO-K1 cells may facilitate
      removal of UV-induced DNA damages partly via its involvement in the repair
      mechanism.

PMID- 17549700
TI  - EGF-like peptides mediate FSH-induced maturation of cumulus cell-enclosed mouse
      oocytes.
AB  - This study was carried out to examine the participation of epidermal growth
      factor (EGF)-like peptides in the induction of germinal vesicle breakdown (GVB)
      in mouse cumulus cell-enclosed oocytes (CEO). The EGF-like peptide, amphiregulin
      (AR), dose-dependently stimulated meiotic resumption in CEO, but not denuded
      oocytes (DO) maintained in meiotic arrest with 300 microM dbcAMP. The EGF
      receptor (EGFR) kinase inhibitor, AG1478, blocked meiotic resumption induced by
      FSH and AR in CEO, but had no effect in DO. FSH-induced maturation was also
      suppressed by antisera to both EGFR and EGF. Maturation occurred with slightly
      faster kinetics in AR-stimulated CEO when compared to FSH-stimulated CEO. When
      CEO were maintained in meiotic arrest with a low level of dbcAMP, FSH was
      initially inhibitory to maturation and later stimulatory; the stimulatory phase
      was prevented by AG1478, indicating mediation by EGF-like peptides. Pulsing CEO
      with high levels of dbcAMP also stimulated GVB and could be blocked by AG1478.
      Treatment of arrested CEO with PKC agonists stimulated maturation and this was
      prevented with AG1478 as well as antibodies to EGFR. FSH-induced maturation of
      dbcAMP-arrested CEO was blocked by bisindolylmaleimide I (BIM-I), an inhibitor of
      PKC, implicating PKC in FSH action. EGF-stimulated CEO failed to resume
      maturation in the presence of glycerrhetinic acid, a gap junction inhibitor,
      suggesting transfer of positive signal through the cell-cell coupling pathway.
      These data support the idea that EGF-like peptides provide a common pathway
      mediating the meiosis-inducing influence of FSH, cAMP pulsing, and PKC activation
      in mouse CEO by a gap junction-dependent process.

PMID- 17549701
TI  - Subchronic (26- and 52-week) toxicity and irritation studies of a novel
      microbicidal gel formulation containing sodium lauryl sulfate in animal models.
AB  - The safety of an ethylene oxide/propylene oxide gel formulation containing sodium
      lauryl sulfate (2%, w/w), that could be a potent candidate as a topical
      microbicide, has been evaluated. More specifically, the subchronic (26- and 52
      week) toxicity of the formulation when applied intravaginally as well as its
      irritating potential for the rectal, penile, eye, skin and buccal mucosa have
      been examined in animal models. The results showed that the vaginal
      administration of the gel formulation containing sodium lauryl sulfate once and
      twice daily (with doses 12 +/- 2 h apart) for 26 weeks to rats and for 52 weeks
      to rabbits induced slight to moderate histopathological alterations. When the
      formulation was applied intrarectally to male and female rabbits once and twice
      daily (with doses 12 +/- 2 h apart) for 14 days, no macroscopic or microscopic
      changes were reported. For both vaginal and rectal dosing, no effect was seen on
      the haematology, coagulation and serum chemistry parameters as well as on the
      body weight of animals and the relative organ weights. Other sporadic macroscopic
      and histopathological findings were incidental in origin and of no toxicological
      significance. The gel formulation containing sodium lauryl sulfate was considered
      as mildly irritating for the penile mucosa of rabbits, non-irritating for the eye
      of rabbits, mildly irritating for the skin in a rabbit model and non-irritating
      for the hamster cheek pouch. It is suggested that the gel formulation containing
      sodium lauryl sulfate is safe for most tissues that could be exposed to the
      product under normal use.

PMID- 17549704
TI  - Repair of large osteochondral defects with allogeneic cartilaginous aggregates
      formed from bone marrow-derived cells using RWV bioreactor.
AB  - Our objective was to examine the technique of regenerating cartilage tissue from
      bone marrow-derived cells by three-dimensional (3D) culture using the rotating
      wall vessel (RWV) bioreactor. Three-dimensional and cylindrical aggregates of
      allogeneic cartilage with dimensions of 10 x 5 mm (height x diameter) formed by
      the RWV bioreactor were transplanted into osteochondral defects of Japanese white
      rabbits (Group T, n = 15). For the control, some osteochondral defects were left
      empty (Group C, n = 18). At 4, 8, and 12 weeks postimplantation, the reparative
      tissues were evaluated macroscopically, histologically, and biochemically. In
      Group T at as early as 4 weeks, histological observation, especially via safranin
      O staining, suggested that the reparative tissues resembled hyaline cartilage.
      And we observed no fibrous tissues between reparative tissue and adjacent normal
      tissues. In the deeper portion of the bony compartment, the osseous tissues were
      well remodeled. At 4 and 8 weeks postimplantation, the mean histological score of
      Group T was significantly better than that of Group C (p < 0.05). The
      glycosaminoglycans (GAG)/DNA ratio in both groups increased gradually from 4 to 8
      weeks and then decreased from 8 to 12 weeks. We herein report the first
      successful regeneration of cartilage in osteochondral defects in vivo using
      allogeneic cartilaginous aggregates derived from bone marrow-derived cells by 3D
      culture using the RWV bioreactor.

PMID- 17549705
TI  - Partial reduction of pyrroles: application to natural product synthesis.
AB  - The partial reduction of N-Boc pyrroles has been explored giving stereoselective
      routes to disubstituted pyrrolines in good yields and with excellent
      diastereoselectivities. A novel methodology has been developed to carry out
      reductive aldol reactions on 2-substituted N-Boc pyrroles; use of aldehydes under
      reductive aldol conditions gave the anti aldol product in good selectivity. This
      chemistry was used as the key transformation in a synthesis of omuralide, which
      was achieved in 13 steps and 14% overall yield. We also report a methodology for
      selectively forming either cis or trans 2,5-disubstituted pyrrolines via a
      partial reduction of an electron-deficient N-Boc pyrrole. The trans pyrroline
      formed using this route was utilized in the syntheses of the polyhydroxylated
      pyrrolizidine natural products hyacinthacine A1 and 1-epiaustraline. Further
      investigation has led to the development of routes to enantiopure substituted
      pyrroline compounds. This has been achieved via a chiral protonation approach
      using easily accessible chiral acids, such as ephedrine and oxazolidinones, to
      quench enolates formed during the partial reduction process. Alternatively,
      enzymatic desymmetrization of symmetrical diol compounds formed from the partial
      reduction products of substituted pyrroles is also reported. This leads to
      formation of both enantiomers of 2,2- and 2,5-disubstituted N-Boc pyrrolines in
      excellent ee and yields.

PMID- 17549706
TI  - Sonoporation mediated transduction of pDNA/siRNA into joint synovium in vivo.
AB  - The purpose of this study was to investigate the usefulness of sonoporation
      method on in vivo transduction of plasmid DNA (pDNA) and small interfering RNA
      (siRNA) into joint tissue. pGEG.GL3 plasmid was mixed with microbubble and
      injected into knee joints of rats. Ultrasound sonication was performed
      percutaneously. Three days after injection, GL3 expression of synovial tissue was
      determined by luciferase assay and RT-PCR. siRNA specific for GL3 (siGL3) or
      nonspecific siRNA were mixed with pGEG.GL3 plasmid and transduced by
      sonoporation. siRNA specific for EGFP (siEGFP) was transduced into the knee
      joints of EGFP transgenic rats, and gene silencing effects for endogenous gene
      were examined. To determine the localization of transduced siRNA, fluorescently
      labeled siRNA was transduced into joints. The expression of GL3 in the synovium
      was significantly enhanced by sonoporation. The gene expression was only seen in
      the synovium of the knee joint. The expression of GL3 was remarkably suppressed
      by co-transduction of siGL3, but not suppressed by nonspecific siRNA. siEGFP
      transduced by sonoporation attenuated green fluorescence on the surface layer of
      synovium of EGFP transgenic rats. The fluorescently labeled siRNA was seen in the
      synovium around the patella, femur, and tibia. Sonoporation is examined as a
      recent, novel, gene transduction method, and the advantage of this technique is
      minimal invasiveness. In this study, we showed that pDNA/siRNA can be transduced
      specifically into the joint synovium using sonoporation. The present method may
      be useful in nucleic acid therapy for joint disorders.

PMID- 17549707
TI  - Patellar blood flow during knee arthroplasty surgical exposure: Intraoperative
      monitoring by laser doppler flowmetry.
AB  - Patellofemoral complications following knee arthroplasty are a well-known
      problem. Patellar ischemia has been suspected to be causative for fracture,
      anterior knee pain, and patella component failure. The purpose of this study was
      to assess the influence of knee arthroplasty surgical dissection on patellar
      blood flow. Patellar blood flow was measured by means of intraosseous laser
      Doppler flowmetry (LDF) in 10 patients undergoing total knee arthroplasty by a
      standard medial parapatellar approach. The initial blood flow was 121.6 +/- 114.7
      AU. The signal significantly decreased by 71% (p = 0.0051) when the knee was
      flexed and lost the pulsatile signal pattern in 80%. After arthrotomy, the signal
      was 100.1 +/- 120.3 AU in extension. The lowest signal was found in flexion and
      eversion of the patella (mean, 18 +/- 10.7 AU) and all signals lost pulsatility.
      As compared to the initial values, completion of the soft tissue dissection did
      not lead to a significant change of the blood flow signal (121.3 +/- 104.8; p =
      0.6835). Flexion of the knee joint markedly reduced patellar perfusion. Standard
      medial parapatellar approach did not significantly change patellar blood flow.
      This study does not support the theory of postoperative patellar ischemia as a
      cause of anterior knee pain or patellofemoral problems.

PMID- 17549715
TI  - Abstracts of the 20th American Peptide Society Symposium, June 26-30, 2007,
      Montreal, Canada.

PMID- 17549708
TI  - Torsional strength estimates of femoral diaphyses with endosteal lytic lesions:
      dual-energy X-ray absorptiometry study.
AB  - Pathologic fracture is a significant problem for individuals with metastatic bone
      disease. Current guidelines for prophylactic internal fixation are neither
      reliable nor easily applied. The purpose of this study was to validate dual
      energy X-ray absorptiometry (DXA) as an accurate method for estimating torsional
      bone strength of diaphyseal bone with endosteal lytic lesions. Endosteal lesions
      of varying sizes were simulated in the diaphyses of 12 adult cadaveric femurs.
      Unaltered contralateral femurs served as matched controls. Machined lesions
      ranged from 3 to 6.5 cm in length, 1 to 3 cm in width, 15 to 48 cm(2) in
      elliptical area, with 10% to 100% removal of the cortical thickness. Morphology
      and density data obtained from DXA images were used to estimate torsional
      strength. All femora were mechanically tested to failure in torsion. Physically
      measured torsional strength was not significantly correlated to lesion elliptical
      area (r = 0.542, p > 0.05) or percentage cortical thickness removed (r = 0.257, p
      > 0.05). Measured torsional strength was significantly correlated to DXA-based
      torsional strength estimates (r = 0.855, p < 0.01). Lesion size alone did not
      correlate with the strength of bones with simulated endosteal lytic lesions. In
      contrast, calculations based on DXA (morphology, density) did correlate with
      torsional strength. This is the first step in the development of a DXA-based tool
      for objectively estimating bone strength in the presence of endosteal lytic
      lesions.

PMID- 17549723
TI  - Synovial fluid recruits human mesenchymal progenitors from subchondral spongious
      bone marrow.
AB  - Microfracture is a frequently used reparative technique that induces a healing
      response in articular cartilage defects. Penetration of the subchondral bone
      leads to blood clot formation, allows multipotent mesenchymal cells to access the
      defect and, subsequently, leads to cartilaginous repair tissue. The aim of our
      study was to analyze the chemotactic recruitment of human subchondral spongious
      bone marrow-derived cells by synovial fluid (SF) from normal donors (ND),
      patients with osteoarthritis (OA) and rheumatoid arthritis (RA). Subchondral
      spongious bone marrow-derived mesenchymal progenitors were isolated from bone
      cylinders after high tibial osteotomy and analyzed for the presence of stem cell
      related cell surface antigens by flow cytometry. Recruitment of subchondral
      progenitors by normal SF and SF from donors with degenerated joint diseases was
      documented by using a modified Boyden chamber chemotaxis assay. The chemotaxis
      assay demonstrated that synovial fluid has the potential to recruit mesenchymal
      progenitors in vitro. SF from normal donors and patients with OA showed no
      difference in the potential to stimulate cell migration. SF obtained from RA
      donors showed significantly reduced cell recruitment compared to SF derived from
      OA patients (p = 0.0054) and normal donors (p < 0.0001). The chemotactic activity
      of SF obtained from normal donors and from patients with degenerative joint
      diseases suggests that SF may be actively involved in the migration of
      progenitors in cartilage defects after microfracture.

PMID- 17549724
TI  - Effect of placental fatty acid metabolism and regulation by peroxisome
      proliferator activated receptor on pregnancy and fetal outcomes.
AB  - Fatty acids, particularly the omega-3 and omega-6 essential fatty acids (EFAs),
      are considered critical nutritional sources for the developing fetus. The
      placenta governs the fetal supply of fatty acids via two processes: transport and
      metabolism. Placental fatty acid metabolism can play a critical role in guiding
      pregnancy and fetal outcome. EFAs can be metabolized to important cell signaling
      molecules in placenta by several major isoform families including: the Cytochrome
      P450 subfamily 4A (CYP4A); Cyclooxygenases (COXs); and Lipoxygenases (LOXs).
      Peroxisome proliferator-activated nuclear receptors (PPARs) have been
      demonstrated to regulate a number of placental fatty acid/lipid homeostasis
      related proteins (e.g., metabolizing enzymes and transporters). The present
      review summarizes research on the molecular and functional relevance of fatty
      acid metabolizing enzymes and the role of PPARs in regulating their expression in
      the mammalian placenta. Elucidating the pathways of placental fatty acid
      metabolism and the regulatory processes governing these pathways is critical for
      advancing our understanding of the role of placenta in supplying EFAs to the
      developing fetus and the potential implications on pregnancy and fetal outcome. A
      more complete understanding of placental fatty acid disposition may also provide
      a basis for nutritional/pharmacological interventions to ameliorate the risk of
      adverse pregnancy and/or fetal outcomes.

PMID- 17549725
TI  - In vitro model of full-thickness cartilage defect healing.
AB  - Integration of the host-graft interface is implicated as one of the significant
      reasons for lack of complete healing in osteochondral grafting procedures for the
      treatment of cartilage lesions. We developed an in vitro model of cartilage
      healing in an osteochondral setting to study the effect of developmental age and
      collagenase treatment. Circular full-thickness vertical surgical incisions were
      made in the cartilaginous portion of cylindrical bovine osteochondral specimens.
      Two age groups were selected: Young (1-2 months old) and Older (6-8 months old).
      Cartilage integration across the surgical incisions was assessed by histologic
      analysis and by mechanical push-out testing at 2 and 4 weeks in culture.
      Histologic integration as well as peak push-out shear stress was significantly
      higher in older calf cartilage than in the young calf. Collagenase pretreatment
      in the older calf samples increased push-out strength at 4 weeks. Histologic
      integration correlated well with the mechanical push-out strength. Developmental
      age and time after injury affected the response to collagenase pretreatment. This
      osteochondral cartilage integration model can be useful to study factors that
      modulate healing of surgical replacement procedures in vitro, which may aid the
      development of newer approaches to promote the healing of cartilage defects.

PMID- 17549726
TI  - Abstracts of the Annual Meeting of the Society of Hospital Medicine. May 24-25,
      2007. Dallas, Texas, USA.

PMID- 17549728
TI  - Patterns of expression of the Follistatin and Follistatin-like1 genes during
      chicken heart development: a potential role in valvulogenesis and late heart
      muscle cell formation.
AB  - The regulation of concentration and function of growth factors is of crucial
      importance to proper embryonic development of the heart. The patterns of
      expression of three extracellular modulators of the transforming growth factor
      beta superfamily of growth factors, Follistatin, Follistatin-like1, and
      Follistatin-like3, are described with respect to heart development. Follistatin
      is highly localized in the endocardium covering the developing cardiac valves.
      Follistatin-like1 is localized in the mesenchymal filling of the pharyngeal
      arches and broadly expressed in cells directly bordering myocardium. Follistatin
      like3 is not expressed in the heart. Taken together, these observations are
      suggestive for a role for Follistatin in cardiac valvulogenesis and a role for
      Follistatin-like1 in controlling late heart muscle cell formation.

PMID- 17549727
TI  - Decoding development in Xenopus tropicalis.
AB  - Xenopus tropicalis is rapidly being adopted as a model organism for developmental
      biology research and has enormous potential for increasing our understanding of
      how embryonic development is controlled. In recent years there has been a well
      organized initiative within the Xenopus community, funded largely through the
      support of the National Institutes of Health in the US, to develop X. tropicalis
      as a new genetic model system with the potential to impact diverse fields of
      research. Concerted efforts have been made both to adapt established
      methodologies for use in X. tropicalis and to develop new techniques. A key
      resource to come out of these efforts is the genome sequence, produced by the US
      Department of Energy's Joint Genome Institute and made freely available to the
      community in draft form for the past three years. In this review, we focus on how
      advances in X. tropicalis genetics coupled with the sequencing of its genome are
      likely to form a foundation from which we can build a better understanding of the
      genetic control of vertebrate development and why, when we already have other
      vertebrate genetic models, we should want to develop genetic analysis in the
      frog.

PMID- 17549729
TI  - Genetic control of basal midbrain development.
AB  - Recent breakthroughs in the understanding of the genetic program that controls
      specification of ventral cell fate in the spinal cord and hindbrain have produced
      useful tools for the study of similar genetic networks in the more complex
      rostral regions of the central nervous system. Several research groups have
      elucidated key factors in the potential signaling processes, as well as
      transcription factors necessary for differentiation of various basal midbrain
      nuclei. Importantly, there has been substantial progress in understanding the
      genetic cascade involved in specifying dopaminergic neurons. This knowledge will
      be crucial in the understanding and possible treatment of Parkinson's disease.

PMID- 17549731
TI  - Hepatocyte growth factor promotes endogenous repair and functional recovery after
      spinal cord injury.
AB  - Many therapeutic interventions using neurotrophic factors or pharmacological
      agents have focused on secondary degeneration after spinal cord injury (SCI) to
      reduce damaged areas and promote axonal regeneration and functional recovery.
      Hepatocyte growth factor (HGF), which was identified as a potent mitogen for
      mature hepatocytes and a mediator of inflammatory responses to tissue injury, has
      recently been highlighted as a potent neurotrophic and angiogenic factor in the
      central nervous system (CNS). In the present study, we revealed that the extent
      of endogenous HGF up-regulation was less than that of c-Met, an HGF receptor,
      during the acute phase of SCI and administered exogenous HGF into injured spinal
      cord using a replication-incompetent herpes simplex virous-1 (HSV-1) vector to
      determine whether HGF exerts beneficial effects and promotes functional recovery
      after SCI. This treatment resulted in the significant promotion of neuron and
      oligodendrocyte survival, angiogenesis, axonal regrowth, and functional recovery
      after SCI. These results suggest that HGF gene delivery to the injured spinal
      cord exerts multiple beneficial effects and enhances endogenous repair after SCI.
      This is the first study to demonstrate the efficacy of HGF for SCI.

PMID- 17549730
TI  - Progesterone increases brain-derived neuroptrophic factor expression and protects
      against glutamate toxicity in a mitogen-activated protein kinase- and
      phosphoinositide-3 kinase-dependent manner in cerebral cortical explants.
AB  - The higher prevalence and risk for Alzheimer's disease in women relative to men
      has been partially attributed to the precipitous decline in gonadal hormone
      levels that occurs in women following the menopause. Although considerable
      attention has been focused on the consequence of estrogen loss, and thus
      estrogen's neuroprotective potential, it is important to recognize that the
      menopause results in a precipitous decline in progesterone levels as well. In
      fact, progesterone is neuroprotective, although the precise mechanisms involved
      remain unclear. Based on our previous observation that progesterone elicits the
      phosphorylation of ERK and Akt, key effectors of the neuroprotective mitogen
      activated protein kinase (MAPK) and phosphoinositide-3 kinase (PI3-K) pathways,
      respectively, we determined whether activation of either of these pathways was
      necessary for progesterone-induced protection. With organotypic explants (slice
      culture) of the cerebral cortex, we found that progesterone protected against
      glutamate-induced toxicity. Furthermore, these protective effects were inhibited
      by either the MEK1/2 inhibitor UO126 or the PI3-K inhibitor LY294002, supporting
      the requirement for both the MAPK and PI3-K pathways in progesterone-induced
      protection. In addition, at a concentration and duration of treatment consistent
      with our neuroprotection data, progesterone also increased the expression of
      brain-derived neurotrophic factor (BDNF), at the level of both protein and mRNA.
      This induction of BDNF may be relevant to the protective effects of progesterone,
      in that inhibition of Trk signaling, with K252a, inhibited the protective effects
      of progesterone. Collectively, these data suggest that progesterone is protective
      via multiple and potentially related mechanisms. (c) 2007 Wiley-Liss, Inc.

PMID- 17549732
TI  - The role of ICOS in the development of CD4 T cell help and the reactivation of
      memory T cells.
AB  - We have addressed the role of the inducible costimulator (ICOS) in the
      development of T cell help for B cells and in the generation, survival and
      reactivation of memory CD4 T cells and B cells. We find that while T cell help
      for all antibody isotypes (including IgG2c) is impaired in ICOS knockout (ICOS
      KO) mice, the IFN-gamma response is little affected, indicating a defect in
      helper function that is unrelated to cytokine production. In addition, the ICOS
      negative T cells do not accumulate in B cell follicles. Secondary (memory), but
      not primary, clonal proliferation of antigen-specific B cells is impaired in ICOS
      KO mice, as is the generation of secondary antibody-secreting cells. Analysis of
      endogenous CD4 memory cells in ICOS-KO mice, using MHC class II tetramers,
      reveals normal primary clonal expansion, formation of memory clones and long-term
      (10 wk) survival of memory cells, but defective expansion upon reactivation in
      vivo. The data point to a role of ICOS in supporting secondary, memory and
      effector T cell responses, possibly by influencing cell survival. The data also
      highlight differences in ICOS dependency of endogenous T cell proliferation in
      vivo compared to that of adoptively transferred TCR-transgenic T cells.

PMID- 17549733
TI  - IL-27 controls the development of inducible regulatory T cells and Th17 cells via
      differential effects on STAT1.
AB  - IL-27 is an IL-12-related cytokine frequently present at sites of inflammation
      that can promote both anti- and pro-inflammatory immune responses. Here, we have
      analyzed the mechanisms how IL-27 may drive such divergent immune responses.
      While IL-27 suppressed the development of proinflammatory Th17 cells, a novel
      role for this cytokine in inhibiting the development of anti-inflammatory,
      inducible regulatory T cells (iTreg) was identified. In fact, IL-27 suppressed
      the development of adaptive, TGF-beta-induced Forkhead box transcription factor
      p3-positive (Foxp3(+)) Treg. Whereas the blockade of Th17 development was
      dependent on the transcription factor STAT1, the suppression of iTreg development
      was STAT1 independent, suggesting that IL-27 utilizes different signaling
      pathways to shape T cell-driven immune responses. Our data thus demonstrate that
      IL-27 controls the development of Th17 and iTreg cells via differential effects
      on STAT1.

PMID- 17549734
TI  - OSP/claudin-11-induced EAE in mice is mediated by pathogenic T cells primarily
      governed by OSP192Y residue of major encephalitogenic region OSP179-207.
AB  - Pathogenic autoimmunity against oligodendrocyte-specific protein (OSP/claudin
      11), recently implicated in multiple sclerosis (MS) pathophysiology, has been
      poorly investigated as compared to that against other myelin encephalitogens.
      Using recombinant soluble mouse OSP (smOSP) and overlapping peptides thereof, we
      show that smOSP-induced chronic EAE in C57BL/6J mice is primarily associated with
      CD4(+) T cells reactive against OSP179-207 and OSP22-46, the major and minor
      encephalitogenic regions, respectively, and with a predominant B cell response
      against OSP22-46. The encephalitogenic OSP179-207-specific T cells recognized
      OSP190-202 as minimal stimulatory epitope, while minimal encephalitogenic
      sequence was OSP191-199. Further delineation and structural bioinformatic
      analysis of the major encephalitogenic region suggested four overlapping
      potential I-A(b) core epitopes, predicting OSP192Y as major TCR-contact residue
      shared by OSP 188-196, OSP190-198, and OSP191-199 cores, albeit at different MHC
      II pockets. Accordingly, substitution at OSP192Y yielded OSP188-192A-202, a non
      stimulatory/non-encephalitogenic altered peptide ligand (APL) that was
      antagonistic for OSP188-202-specific encephalitogenic T cells. Systemic
      administration of OSP188-192A-202 suppressed OSP188-202-induced EAE and fully
      reversed smOSP-induced EAE. These data suggest that a single epitopic residue
      (OSP192Y) governs the selection and control of most pathogenic T cells associated
      with smOSP-induced EAE in H-2(b) mice. This may impact profoundly on peripheral
      self-tolerance to OSP and on potential APL-mediated therapy of OSP-related
      autoimmune pathogenesis.

PMID- 17549735
TI  - Fast-tracked CTL: rapid induction of potent anti-tumor killer T cells in situ.
AB  - Current strategies to elicit cytolytic T cell responses specific for tumor
      associated or over-expressed self antigens rely on multiple immunizations and in
      vitro expansion schemes. Here we report the in vivo induction of activated tumor
      specific CD8(+) CTL just 6 days after treatment with the IgM immune modulator B7
      DC XAb. Antibody treatment of mice at the time of tumor challenge elicited potent
      CTL with a specificity that distinguished between MHC-compatible tumors.
      Remarkably, these effector cells were not generated by the extensive
      proliferation of naive CTL precursors, though their induction required CD4(+) T
      cell help and classical B7 costimulatory signals. Tumor targets were recognized
      and lysed in an MHC-restricted, perforin-dependent manner, indicating that these
      rapidly induced effectors resemble traditionally defined CTL, despite the finding
      that strong increases in the expression of the effector/memory marker CD44 and
      the activation marker CD69 were not elicited. These CTL were induced in animals
      bearing well-established tumors and resulted in anti-tumor protection,
      underscoring the therapeutic potential of this type of effector T cell population
      in cancer patients.

PMID- 17549736
TI  - A homodimeric complex of HLA-G on normal trophoblast cells modulates antigen
      presenting cells via LILRB1.
AB  - In healthy individuals, the non-classical MHC molecule HLA-G is only expressed on
      fetal trophoblast cells that invade the decidua during placentation. We show that
      a significant proportion of HLA-G at the surface of normal human trophoblast
      cells is present as a disulphide-linked homodimer of the conventional beta(2)m
      associated HLA-I complex. HLA-G is a ligand for leukocyte immunoglobulin-like
      receptors (LILR), which bind much more efficiently to dimeric HLA-G than to
      conventional HLA-I molecules. We find that a LILRB1-Fc fusion protein
      preferentially binds the dimeric form of HLA-G on trophoblast cells. We detect
      LILRB1 expression on decidual myelomonocytic cells; therefore, trophoblast HLA-G
      may modulate the function of these cells. Co-culture with HLA-G(+) cells does not
      inhibit monocyte-derived dendritic cell up-regulation of HLA-DR and costimulatory
      molecules on maturation, but did increase production of IL-6 and IL-10.
      Furthermore, proliferation of allogeneic lymphocytes was inhibited by HLA-G
      binding to LILRB1/2 on responding antigen-presenting cells (APC). As HLA-G is the
      only HLA-I molecule that forms beta(2)m-associated dimers with increased avidity
      for LILRB1, this interaction could represent a placental-specific signal to
      decidual APC. We suggest that the placenta is modulating maternal immune
      responses locally in the uterus through HLA-G, a trophoblast-specific,
      monomorphic signal present in almost every pregnancy. See accompanying
      commentary: (http://dx.doi.org/10.1002/eji.200737515).

PMID- 17549737
TI  - Gut flora antigens are not important in the maintenance of regulatory T cell
      heterogeneity and homeostasis.
AB  - CD25(+) regulatory T cells (Treg) are a heterogeneous population that exists as
      CD44(low) and CD44(high) cells. Here we report that while both CD44(low) and
      CD44(high) Treg are anergic and express similar levels of Foxp3, CD44(high) Treg
      are highly proliferative in vivo and are more potent suppressors in vitro than
      CD44(low) Treg. From analysis of the properties of Treg derived from germ-free
      mice, it was concluded that peptide antigens derived from intestinal
      microorganisms are not essential for the generation, in vivo proliferation or
      suppressive activity of Treg. Our results suggest that gut flora antigens play
      little or no role in the heterogeneity and homeostatic regulation of Treg.

PMID- 17549738
TI  - Flagellar and ciliary beating in trypanosome motility.
AB  - The single flagellum of Leishmania and Trypanosoma parasites is becoming an
      increasingly attractive model for the analysis of flagellar function-driven
      largely by the abundance of genomic and proteomic information available for the
      organelle, the genetic manipulability of the organisms and the importance of
      motility for the parasite lifecycle. However, as yet, there is a paucity of
      published data on the beating of any genetically malleable trypanosomatid
      species. Here we undertook an in-depth analysis using high-speed videomicroscopy
      of the beating of free-swimming Leishmania major cells in comparison to Crithidia
      species (for which there is some existing literature). In so doing, we describe a
      simple and generally-applicable technique to facilitate the quantitative analysis
      of free-swimming cells. Our analysis thoroughly defines the parameters of the
      expected tip-to-base symmetrical flagellar beat in these species. It also
      describes beat initiation from points other than the flagellum tip and a
      completely different, base-to-tip highly-asymmetric beat that represents a
      ciliary beat of trypanosomatid flagella. Moreover, detailed analysis of parameter
      interrelationships revealed an unexpected dependency of wavelength on oscillator
      length that may be the result of reversible constraint of doublet sliding at the
      tip or resonance of the flagellar beat.

PMID- 17549739
TI  - The quest for circulating endothelial cell standardization: the peril of
      platelets.

PMID- 17549740
TI  - Indirect immunofluorescence in autoimmune diseases: assessment of digital images
      for diagnostic purpose.
AB  - BACKGROUND: The recommended method for antinuclear antibodies (ANA) detection is
      indirect immunofluorescence (IIF). To pursue a high image quality without
      artefacts and reduce interobserver variability, this study aims at evaluating the
      reliability of automatically acquired digital images of IIF slides for diagnostic
      purposes. METHODS: Ninety-six sera were screened for ANA by IIF on HEp-2 cells.
      Two expert physicians looking at both the fluorescence microscope and the digital
      images on computer monitor performed a blind study to evaluate fluorescence
      intensity and staining pattern. Cohen's kappa was used as an agreement evaluator
      between methods and experts. RESULTS: Considering fluorescence intensity, there
      is a substantial agreement between microscope and monitor analysis in both
      physicians. Agreement between physicians was substantial at the microscope and
      perfect at the monitor. Considering IIF pattern, there was a substantial and
      moderate agreement between microscope and monitor analysis in both physicians.
      Kappa between physicians was substantial both at the microscope and at the
      monitor. CONCLUSIONS: These preliminary results suggest that digital media is a
      reliable tool to help physicians in detecting autoantibodies in IIF. Our data
      represent a first step to validate the use of digital images, thus offering an
      opportunity for standardizing and automatizing the detection of ANA by IIF.

PMID- 17549742
TI  - Recent advances in the diagnosis, monitoring, and management of patients with
      paroxysmal nocturnal hemoglobinuria.
AB  - Until recently, there has been no specific therapy for PNH with clinical
      management mainly supportive in terms of cytopenias and control of thrombotic
      risk. Currently, the only curative procedure for PNH is bone marrow
      transplantation although for the majority of patients the associated risks are
      too great to justify transplantation. The pioneering use of the therapeutic
      monoclonal antibody eculizumab, which binds to and prevents the activation of the
      complement protein C5, represents a significant advance in treatment for patients
      with PNH and is set to become the future standard therapy for hemolytic PNH. In
      both an initial pilot study and two phase III clinical trials, eculizumab has
      been shown to dramatically reduce intravascular hemolysis, hemoglobinuria, and
      transfusion requirements thus improving the quality of life in patients with PNH.
      As a clinical entity, PNH is synonymous with glycosylphosphatidylinositol (GPI)
      deficiency, and is an acquired clonal disorder associated with somatic mutations
      of the X-linked PIGA gene in hematopoietic stem cells. A recent study identified
      a novel autosomal recessively inherited form of GPI-deficiency involving a
      mutation in a promotor component of the pig-m gene and characterized by a
      thrombotic tendency and seizures. In both these developments, flow cytometry
      played a critical role. In the first instance, in monitoring direct response to a
      new therapeutic agent; second, in demonstrating the phenotypic/genotypic link in
      a new form of GPI deficiency.

PMID- 17549743
TI  - Powerful designs for genetic association studies that consider twins and sibling
      pairs with discordant genotypes.
AB  - Genetic association studies are becoming commonplace due to the availability of
      cost-effective yet sophisticated DNA sequencing and genotyping resources and
      technologies. In addition, technologies designed to identify molecular and
      subclinical phenotypes that reflect disease pathogenesis are continually being
      developed and refined (consider, e.g., imaging technologies, microarray-based
      gene expression and proteomic platforms, histological analyses of excised
      tissues, etc.). Unfortunately, the large-scale use of many of these molecular and
      subclinical phenotyping technologies in genetic association studies is difficult
      logistically and is currently cost-prohibitive. In this paper, we consider
      efficient designs for testing the association between particular genetic
      variations and expensive, yet appropriate, subclinical phenotypes of relevance to
      a disease that take advantage of twins or sibling pairs discordant for genotypes
      at the locus (or loci) being tested. We demonstrate that including genotypically
      discordant twins or siblings in an association study can result in a substantial
      increase in power over designs that use monozygotic twins or only unrelated
      individuals. We ultimately argue that, from a practical standpoint, sampling from
      existing family or twin-based cohorts in which: (1) follow-up studies of a
      genetic association are warranted in order to assess the in vivo significance of
      an association with respect to more refined pathological phenotypes; and/or (2)
      large-scale, genome-wide linkage and association studies have been pursued that
      have focused on clinical endpoints for which the study subjects have consented to
      more elaborate follow-up studies, is a powerful way to test associations.

PMID- 17549744
TI  - Keeping an eye on I1: I1 dynein as a model for flagellar dynein assembly and
      regulation.
AB  - Among the major challenges in understanding ciliary and flagellar motility is to
      determine how the dynein motors are assembled and localized and how dynein-driven
      outer doublet microtubule sliding is controlled. Diverse studies, particularly in
      Chlamydomonas, have determined that the inner arm dynein I1 is targeted to a
      unique structural position and is critical for regulating the microtubule sliding
      required for normal ciliary/flagellar bending. As described in this review, I1
      dynein offers additional opportunities to determine the principles of assembly
      and targeting of dyneins to cellular locations and for studying the mechanisms
      that regulate dynein activity and control of motility by phosphorylation.

PMID- 17549745
TI  - Impact of a bedside procedure service on general medicine inpatients: A firm
      based trial.
AB  - BACKGROUND: Procedure services may improve the training of bedside procedures.
      However, little is known about how procedure services may affect the demand for
      and success of procedures performed on general medicine inpatients. OBJECTIVE:
      Determine whether a procedure service affects the number and success of 4 bedside
      procedures (paracentesis, thoracentesis, lumbar puncture, and central venous
      catheterization) attempted on general medicine inpatients. DESIGN: Prospective
      cohort study. SETTING: Large public teaching hospital. PATIENTS: Nineteen hundred
      and forty-one consecutive admissions to the general medicine service.
      INTERVENTION: A bedside procedure service was offered to physicians from 1 of 3
      firms for 4 weeks. This service then crossed over to physicians from the other 2
      firms for another 4 weeks. MEASUREMENTS: Data on all procedure attempts were
      collected daily from physicians. We examined whether the number of attempts and
      the proportion of successful attempts differed based on whether firms were
      offered the beside procedure service. RESULTS: The number of procedure attempts
      was 48% higher in firms offered the service (90 versus 61 per 1000 admissions; RR
      1.48, 95% CI 1.06-2.10; P = .030). More than 85% of the observed increase was a
      result of procedures with therapeutic indications. There were no differences
      between firms in the proportions of successful attempts or major complications.
      CONCLUSIONS: The availability of a procedure service may increase the overall
      demand for bedside procedures. Further studies should refine the indications for
      and anticipated benefits from these commonly performed invasive procedures.

PMID- 17549746
TI  - Olfactory axon guidance: the modified rules.
AB  - The olfactory system represents a complex model for the investigation of factors
      that influence the guidance of sensory axon populations to specific targets in
      the CNS. In the mouse, the projections of approximately 1,000 neuronal subsets,
      each defined by expression of a distinct odorant receptor (OR), converge at
      unique glomerular loci in the olfactory bulb (OB). Unlike the case in other
      sensory systems, proper guidance is achieved without benefit of any known cues in
      the target itself that are capable of attracting or repelling specific axons. It
      has long been argued that OR proteins are the critical molecules orchestrating
      guidance. However, recent studies suggest that axon identity may be dependent on
      the graded expression of a variety of unique olfactory axon guidance cues. This
      review focuses attention on these non-OR factors and their roles in olfactory
      axon guidance.

PMID- 17549748
TI  - Myotonic dystrophy 1 in the nervous system: from the clinic to molecular
      mechanisms.
AB  - Myotonic dystrophy type 1 (DM1) is a dominant neuromuscular disorder caused by
      the expansion of trinucleotide CTG repeats in the 3'-untranslated region (3'-UTR)
      of the DMPK gene. Prominent features of classical DM1 are muscle wasting and
      myotonia, whereas mental retardation is distinctive for congenital DM1. The main
      nervous system symptoms of DM1 are cognitive impairment, neuroendocrine
      dysfunction, and personality and behavior abnormalities. It is thought that
      expansion of CTG repeats causes DM1 pathology through different molecular
      mechanisms; however, a growing body of evidence indicates that an RNA gain-of
      function mechanism plays a major role in the disease development. At the skeletal
      muscle level, three main molecular events can be distinguished in this model: 1)
      formation of nuclear foci that are composed at least of mutant DMPK mRNA and
      recruited RNA-binding proteins, such as splicing regulators and transcription
      factors; 2) disturbance of alternative splicing of specific genes; and 3)
      impairment of cell differentiation. Contrasting with the substantial advances in
      understanding DM1 muscle pathology, the molecular basis of DM1 in the nervous
      system has just started to be revealed. This review focuses in the DM1 nervous
      system pathology and provides an overview of the genetic and molecular studies
      analyzing the effects of the DMPK gene CUG expanded repeats on cell function in
      neuronal systems. A comparison between the molecular mechanisms of DM1 in the
      skeletal muscle and those identified in DM1 nervous system models is provided.
      Finally, future directions in the study of DM1 in the nervous system are
      discussed.

PMID- 17549747
TI  - No effect of genetic deletion of contactin-associated protein (CASPR) on axonal
      orientation and synaptic plasticity.
AB  - Myelinated axons are endowed with a specialized domain structure that is
      essential for saltatory action potential conduction. The paranodal domain
      contains the axoglial junctions and displays a unique ultrastructure that
      resembles the invertebrate septate junctions (SJs). Biochemical characterizations
      of the paranodal axoglial SJs have identified several molecular components that
      include Caspr and contactin (Cont) on the axonal side and neurofascin 155 kDa
      (NF155) isoform on the glial side. All these proteins are essential for the
      formation of the axoglial SJs. Based on the interactions between Caspr and Cont
      and their colocalization in the CA1 synaptic areas, it was proposed that the
      synaptic function of Cont requires Caspr. Here we have extended the phenotypic
      analysis of CASPR mutants to address further the role of Caspr at the axoglial
      SJs and also in axonal orientation and synaptic plasticity. We report that, in
      CASPR mutants, the smooth endoplasmic reticulum (SER) forms elongated membranous
      complexes that accumulate at the nodal/paranodal region and stretch into the
      juxtaparanodal region, a defect that is consistent with the paranodal
      disorganization. We show that the cerebellar microorganization is unaffected in
      CASPR mutants. We also demonstrate that Caspr function is not essential for
      normal CA1 synaptic transmission and plasticity. Taken together with previous
      findings, our results highlight that the Caspr/Cont complex is essential for the
      formation of axoglial SJs, whereas Cont may regulate axonal orientation and
      synaptic plasticity independent of its association with Caspr.

PMID- 17549749
TI  - Comparison of resource utilization and clinical outcomes between teaching and
      nonteaching medical services.
AB  - PURPOSE: To compare the resource utilization and clinical outcomes of medical
      care delivered on general internal medicine inpatient services at teaching and
      nonteaching services at an academic hospital. METHODS: From February to October
      2002, 2189 patients admitted to a 450-bed university-affiliated community
      hospital were assigned either to a resident-staffed teaching service (n = 1637)
      or to a hospitalist- or clinic-based internist nonteaching service (n = 552). We
      compared total hospital costs per patient, length of hospital stay (LOS),
      hospital readmission within 30 days, in-hospital mortality, and costs for
      pharmacy, laboratory, radiology, and others between teaching and nonteaching
      services. RESULTS: Care on a teaching service was not associated with increased
      overall patient care costs ($5572 vs. $5576; P = .99), LOS (4.92 days vs. 5.10
      days; P = .43), readmission rate (12.3% vs. 10.3%; P = .21), or in-hospital
      mortality (3.7% vs. 4.5%; P = .40). Mean laboratory and radiology costs were
      higher on the teaching service, but costs for the pharmacy and for speech
      therapy, occupational therapy, physical therapy, respiratory therapy, pulmonary
      function testing, and GI endoscopy procedures were not statistically different
      between the 2 services, and residents did not order more tests or procedures.
      Case mix and illness severity, as reflected by the distribution of the most
      frequent DRGs and mean number of secondary diagnoses per patient and DRG-specific
      LOS, were similar on the 2 services. CONCLUSIONS: At our academic hospital,
      admission to a general internal medicine teaching service resulted in patient
      care costs and clinical outcomes comparable to those admitted to a nonteaching
      service.

PMID- 17549750
TI  - Increased cerebral oxygen consumption in Eker rats and effects of N-methyl-D
      aspartate blockade: Implications for autism.
AB  - Because there is a strong correlation between tuberous sclerosis and autism, we
      used a tuberous sclerosis model (Eker rat) to test the hypothesis that these
      animals would have an altered regional cerebral O2 consumption that might be
      associated with autism. We also examined whether the altered cerebral O2
      consumption was related to changes in the importance of N-methyl-D-aspartate
      (NMDA) receptors. Young (4 weeks) male control Long Evans (N = 14) and Eker (N =
      14) rats (70-100 g) were divided into control and CGS-19755 (10 mg/kg,
      competitive NMDA antagonist)-treated animals. Cerebral regional blood flow (14C
      iodoantipyrine) and O2 consumption (cryomicrospectrophotometry) were determined
      in isoflurane-anesthetized rats. NMDA receptor protein levels were determined by
      Western immunoblotting. We found significantly increased basal O2 consumption in
      the cortex (6.2 +/- 0.6 ml O2/min/100 g Eker vs. 4.7 +/- 0.4 Long Evans),
      hippocampus, cerebellum, and pons. Regional cerebral blood flow was also elevated
      in Eker rats at baseline, but cerebral O2 extraction was similar. CGS-19755
      significantly lowered O2 consumption in the cortex (2.8 +/- 0.3), hippocampus,
      and pons of the Long Evans rats but had no effect on cortex (5.8 +/- 0.8) or
      other regions of the Eker rats. Cerebral blood flow followed a similar pattern.
      NMDA receptor protein levels (NR1 subunit) were similar between groups. In
      conclusion, Eker rats had significantly elevated cerebral O2 consumption and
      blood flow, but this was not related to NMDA receptor activation. In fact, the
      importance of NMDA receptors in the control of basal cerebral O2 consumption was
      reduced. This might have important implications in the treatment of autism.

PMID- 17549751
TI  - Including sampling and phenotyping costs into the optimization of two stage
      designs for genomewide association studies.
AB  - We propose optimized two-stage designs for genome-wide case-control association
      studies, using a hypothesis testing paradigm. To save genotyping costs, the
      complete marker set is genotyped in a sub-sample only (stage I). On stage II, the
      most promising markers are then genotyped in the remaining sub-sample. In recent
      publications, two-stage designs were proposed which minimize the overall
      genotyping costs. To achieve full design optimization, we additionally include
      sampling costs into both the cost function and the design optimization. The
      resulting optimal designs differ markedly from those optimized for genotyping
      costs only (partially optimized designs), and achieve considerable further cost
      reductions. Compared with partially optimized designs, fully optimized two-stage
      designs have higher first-stage sample proportion. Furthermore, the increment of
      the sample size over the one-stage design, which is necessary in two-stage
      designs in order to compensate for the loss of power due to partial genotyping,
      is less pronounced for fully optimized two-stage designs. In addition, we address
      the scenario where the investigator is interested to gain as much information as
      possible, however is restricted in terms of a budget. In that we develop two
      stage designs that maximize the power under a certain cost constraint.

PMID- 17549752
TI  - Optimal designs for two-stage genome-wide association studies.
AB  - Genome-wide association (GWA) studies require genotyping hundreds of thousands of
      markers on thousands of subjects, and are expensive at current genotyping costs.
      To conserve resources, many GWA studies are adopting a staged design in which a
      proportion of the available samples are genotyped on all markers in stage 1, and
      a proportion of these markers are genotyped on the remaining samples in stage 2.
      We describe a strategy for designing cost-effective two-stage GWA studies. Our
      strategy preserves much of the power of the corresponding one-stage design and
      minimizes the genotyping cost of the study while allowing for differences in per
      genotyping cost between stages 1 and 2. We show that the ratio of stage 2 to
      stage 1 per genotype cost can strongly influence both the optimal design and the
      genotyping cost of the study. Increasing the stage 2 per genotype cost shifts
      more of the genotyping and study cost to stage 1, and increases the cost of the
      study. This higher cost can be partially mitigated by adopting a design with
      reduced power while preserving the false positive rate or by increasing the false
      positive rate while preserving power. For example, reducing the power preserved
      in the two-stage design from 99 to 95% that of the one-stage design decreases the
      two-stage study cost by approximately 15%. Alternatively, the same cost savings
      can be had by relaxing the false positive rate by 2.5-fold, for example from
      1/300,000 to 2.5/300,000, while retaining the same power.

PMID- 17549753
TI  - Spinal AMPA receptor inhibition attenuates mechanical allodynia and neuronal
      hyperexcitability following spinal cord injury in rats.
AB  - In this study, we examined whether a competitive AMPA receptor antagonist, NBQX,
      attenuates mechanical allodynia and hyperexcitability of spinal neurons in
      remote, caudal regions in persistent central neuropathic pain following spinal
      cord injury in rats. Spinal cord injury was produced by unilateral T13 transverse
      spinal hemisection, from dorsal to ventral, in male Sprague Dawley rats (200-250
      g). Mechanical thresholds were measured behaviorally, and the excitability of
      wide-dynamic-range (WDR) dorsal horn neurons in the lumbar cord (L4-L5) was
      measured to assess central neuropathicpain. On postoperation day (POD) 28 after
      spinalhemisection, mechanical thresholds were significantly decreased in both
      injured (ipsilateral) and noninjured (contralateral) hindpaws compared with
      preinjury and sham control, respectively (P < 0.05). Intrathecal administration
      of NBQX (0.25, 0.5, 1 mM) significantly reversed the decreased mechanical
      thresholds in both hindpaws, dose dependently (P < 0.05). The excitability of WDR
      neurons was significantly enhanced on both sides of the lumbar dorsal horn 28
      days following spinal hemisection (P < 0.05). The hyperexcitability of WDR
      neurons was attenuated by topical administration of NBQX (0.125, 0.25, 0.5, 1
      mM), dose dependently (P < 0.05). Regression analysis indicated that at least
      three molecules of NBQX bond per receptor complex, and are needed to achieve
      inhibition of WDR hyperexcitability. In conclusion, our study demonstrates that
      the AMPA receptor plays an important role in behaviors related to the maintenance
      of central neuropathic pain below the level of spinal cord injury.

PMID- 17549754
TI  - Minocycline modulates chemokine receptors but not interleukin-10 mRNA expression
      in hypoxic-ischemic neonatal rat brain.
AB  - Hypoxic-ischemic (HI) brain injury in the perinatal period causes significant
      morbidity. Minocycline (MN) is a tetracycline derivative that has reduced brain
      injury in various animal models of neurodegeneration, including perinatal
      ischemia. To determine whether MN can modulate the expression of chemokine
      receptors and interleukin-10 (IL10) in a model of neonatal brain injury, we
      produced an HI insult to the right cerebral hemisphere (ipsilateral) of the 7-day
      old rat (PD7) by right common carotid artery ligation and 2.25 hr of hypoxia in
      8% oxygen. MN (45 mg/kg, i.p.) or vehicle (PBS) was injected twice: 2 days and
      immediately before the HI insult. At 0, 1, 3, and 24 hr and 14 days after HI,
      total RNA from the ipsilateral and contralateral (exposed to hypoxia only)
      hemispheres was extracted, reverse transcribed, and amplified with gene-specific
      primers using a semiquantitative RT-PCR for macrophage inflammatory protein
      1alpha), interferon-inducible protein (IP-10), C-C chemokine receptor 5 (CCR5;
      MIP-1alpha receptor), C-X-C chemokine receptor 3 (CXCR3; IP-10 receptor), and
      IL10. We found that, in the ipsilateral hemisphere, a significant (P < 0.05)
      increase in MIP-1alpha, IP-10, CCR5, and CXCR3 mRNA levels was observed. MN
      treatment decreased mRNA levels for CCR5 and CXCR3. In contrast, the levels of
      antiinflammatory cytokine IL10 were markedly decreased as a result of HI insult.
      Treatment with MN, however, had no effect on IL10. We conclude that MN decreased
      proinflammatory chemokine receptor expression but had little or no influence on
      the expression of antiinflammatory cytokine IL10. These effects confirm the
      antiinflammatory effect of MN in neonatal HI brain injury.

PMID- 17549755
TI  - Neural plasticity of neonatal hypoglossal nerve for effective suckling.
AB  - The adaptive movement of the tongue after unilateral lesion of the hypoglossal
      (XII) nerve during the early postnatal days is essential for recovery of milk
      intake. The present study investigated the basic mechanisms underlying such
      adaptation, focusing on the neural plasticity that allows effective suckling.
      After resection of the ipsilateral XII nerve on P1, 1,1'-dioctadecyl-3,3,3',3'
      tetramethylindocarbocyanine perchlolate (DiI), a postmortem neuronal tracer, was
      applied to the contralateral uninjured XII nerve on P4 and P7. DiI-labeled fibers
      were traced successfully within the tongue and showed gradually increased
      extension over the XII nerve-injured side in the central core portion of the
      denervated tongue between P4 and P7. Systematic neuroanatomic experiments showed
      that contralateral axonal sprouting occurred as early as 1 day after nerve injury
      (P2), and that such axonal sprouting occurred exclusively from the medial branch
      of the XII nerve responsible for tongue protrusion, an essential movement for
      suckling. These findings provide direct evidence of functional neural plasticity
      that allows effective suckling in XII nerve-injured newborns with suckling
      disturbance.

PMID- 17549757
TI  - Quantitative trait association in parent offspring trios: Extension of
      case/pseudocontrol method and comparison of prospective and retrospective
      approaches.
AB  - The case/pseudocontrol method provides a convenient framework for family-based
      association analysis of case-parent trios, incorporating several previously
      proposed methods such as the transmission/disequilibrium test and log-linear
      modelling of parent-of-origin effects. The method allows genotype and haplotype
      analysis at an arbitrary number of linked and unlinked multiallelic loci, as well
      as modelling of more complex effects such as epistasis, parent-of-origin effects,
      maternal genotype and mother-child interaction effects, and gene-environment
      interactions. Here we extend the method for analysis of quantitative as opposed
      to dichotomous (e.g. disease) traits. The resulting method can be thought of as a
      retrospective approach, modelling genotype given trait value, in contrast to
      prospective approaches that model trait given genotype. Through simulations and
      analytical derivations, we examine the power and properties of our proposed
      approach, and compare it to several previously proposed single-locus methods for
      quantitative trait association analysis. We investigate the performance of the
      different methods when extended to allow analysis of haplotype, maternal genotype
      and parent-of-origin effects. With randomly ascertained families, with or without
      population stratification, the prospective approach (modeling trait value given
      genotype) is found to be generally most effective, although the retrospective
      approach has some advantages with regard to estimation and interpretability of
      parameter estimates when applied to selected samples.

PMID- 17549758
TI  - Computer-based multivariate economic analysis of neonatal-intensive-care-unit
      based influenza vaccine administration to parents in a low-socio-economic, urban
      setting.
AB  - OBJECTIVE: Trivalent inactivated influenza vaccine has been shown to reduce the
      number of influenza-related outpatient visits and hospitalizations of children up
      to 24 months of age. The American Academy of Pediatrics, Centers for Disease
      Control, and Advisory Committee on Immunization Practices recommend that the
      influenza vaccine be administered to the first-person contacts of infants less
      than 6 months of age. However, the economic implications of increasing
      immunization rates by using the neonatal intensive care unit (NICU) as an arena
      to capture the parents of these infants has not been fully evaluated. We sought
      to examine the direct and indirect costs of a program to administer the influenza
      vaccine to parents in the NICUs of a cohort of tertiary-care units primarily
      serving a low socioeconomic population. METHODS: The probabilities of infants
      being hospitalized because of infection from contact and of the efficacy of
      prophylaxis used in the present study were based on published results where
      possible, with an estimated 10% reduction in hospitalization of patients whose
      parents had received the vaccine. Variables in the 3- and 4-tiered analyses
      included chronic lung disease status, estimation if patients had siblings,
      vaccination status of siblings, seroconversion rate of vaccine, and parental
      vaccination status. Two thousand six hundred and thirty-two patients were
      analyzed using 2003 admission data from the New York City Regional Perinatal
      Center, which encompasses 11 level III NICUs. Hospitalization costs, indirect
      costs, and outpatient costs were assessed using previously published standard
      calculations. RESULTS: On the basis of this computer model, costs were $188 per
      patient per influenza season, including $6.80 per patient in outpatient costs.
      Administration of an NICU-based influenza vaccine increased costs to $200 per
      patient per influenza season, but decreased outpatient costs to $1.40 per
      patient. For cost savings to equal costs of vaccine administration, there must be
      either a 20% reduction in influenza hospitalizations of NICU patients or an
      increase in the sample size per influenza season to 4000 patients. CONCLUSIONS:
      The cost of administration of the influenza vaccine to parents of NICU patients
      is higher than the financial burden of influenza in this population as long as
      the sibling immunization rate remains low. Cost savings do not occur until the
      treated cohort increases to 4000 patients or the incidence of lung disease in
      this population increases. Further studies are needed to validate the cost
      savings of this mode and more accurately assess the financial savings.

PMID- 17549759
TI  - Conflicting measures of hospital quality: ratings from "Hospital Compare" versus
      "Best Hospitals".
AB  - BACKGROUND: In April 2005 the Centers for Medicare and Medicaid Services launched
      "Hospital Compare," the first government-sponsored hospital quality scorecard. We
      compared the ranking of U.S. News and World Report's "Best Hospitals" with
      Hospital Compare performance ratings. METHODS: We examined Hospital Compare
      scores for core measures related to care for acute myocardial infarction (AMI),
      congestive heart failure (CHF), and community-acquired pneumonia (CAP). We
      calculated composite scores for the disease-specific sets of core measures and a
      composite combined score for the 14 core measures (across 3 diseases) and
      determined national score quartile cut points for each set. We then characterized
      the quartile distribution of Hospital Compare scores for the Best Hospitals for
      care of cardiac conditions and respiratory disorders in each year, as well as for
      the Best Hospital "Honor Roll" institutions. RESULTS: AMI scores were available
      for 2165 hospitals, CHF scores for 3130, and CAP scores for 3462. In both 2004
      and 2005, fewer than 50% of the Best Hospitals for cardiac care rated in the top
      quartile of Hospital Compare scores for AMI and CHF. Among the Best Hospitals for
      care of respiratory disorders, fewer than 15% scored in the top Hospital Compare
      quartile for CAP. Among Honor Roll institutions, only 5 (of 14 hospitals in 2004;
      of 16 in 2005) ranked in the top quartile for the combined core measure score.
      CONCLUSIONS: Hospital Compare scores are frequently discordant with Best Hospital
      rankings, which is likely attributable to the markedly different methods each
      rating approach employs. Such discordance between major quality rating systems
      paints a conflicting picture of institutional performance for the public to
      interpret.

PMID- 17549760
TI  - Improving power in genome-wide association studies: weights tip the scale.
AB  - The potential of genome-wide association analysis can only be realized when they
      have power to detect signals despite the detrimental effect of multiple testing
      on power. We develop a weighted multiple testing procedure that facilitates the
      input of prior information in the form of groupings of tests. For each group a
      weight is estimated from the observed test statistics within the group.
      Differentially weighting groups improves the power to detect signals in likely
      groupings. The advantage of the grouped-weighting concept, over fixed weights
      based on prior information, is that it often leads to an increase in power even
      if many of the groupings are not correlated with the signal. Being data
      dependent, the procedure is remarkably robust to poor choices in groupings. Power
      is typically improved if one (or more) of the groups clusters multiple tests with
      signals, yet little power is lost when the groupings are totally random. If there
      is no apparent signal in a group, relative to a group that appears to have
      several tests with signals, the former group will be down-weighted relative to
      the latter. If no groups show apparent signals, then the weights will be
      approximately equal. The only restriction on the procedure is that the number of
      groups be small, relative to the total number of tests performed.

PMID- 17549761
TI  - Testing association for markers on the X chromosome.
AB  - Test statistics for association between markers on autosomal chromosomes and a
      disease have been extensively studied. No research has been reported on
      performance of such test statistics for association on the X chromosome. With
      100,000 or more single-nucleotide polymorphisms (SNPs) available for genome-wide
      association studies, thousands of them come from the X chromosome. The X
      chromosome contains rich information about population history and linkage
      disequilibrium. To identify X-linked marker susceptibility to a disease, it is
      important to study properties of various statistics that can be used to test for
      association on the X chromosome. In this article, we compare performance of
      several approaches for testing association on the X chromosome, and examine how
      departure from Hardy-Weinberg equilibrium would affect type I error and power of
      these association tests using X-linked SNPs. The results are applied to the X
      chromosome of Klein et al. [2005], a genome-wide association study with 100K SNPs
      for age-related macular degeneration. We found that a SNP (rs10521496) covered by
      DIAPH2, known to cause premature ovarian failure (POF) in females, is associated
      with age-related macular degeneration.

PMID- 17549762
TI  - Detecting haplotype effects in genomewide association studies.
AB  - The analysis of genomewide association studies requires methods that are both
      computationally feasible and statistically powerful. Given the large-scale
      collection of single nucleotide polymorphisms (SNPs), it is desirable to explore
      the information contained in their interrelationships. In particular, utilizing
      haplotypes rather than individual SNPs and accounting for correlations of
      polymorphisms in adjustment for multiple testing can lead to increased power. We
      present a statistically powerful and numerically efficient method based on
      sliding windows of adjacent SNPs to detect haplotype-disease association in
      genomewide studies. This method consists of an efficient algorithm to calculate a
      proper likelihood-ratio statistic for any given window of SNPs, along with an
      accurate and efficient Monte Carlo procedure to adjust for multiple testing.
      Simulation studies using the HapMap data showed that the proposed method performs
      well in realistic situations. We applied the new method to a case-control study
      on rheumatoid arthritis and identified several loci worthy of further
      investigations.

PMID- 17549763
TI  - Labeling of apoptotic JURL-MK1 cells by fluorescent caspase-3 inhibitor FAM-DEVD
      fmk occurs mainly at site(s) different from caspase-3 active site.
AB  - BACKGROUND: Fluorochrome-labeled inhibitors of caspases (FLICA) have been
      designed as an alternative tool for the detection of caspase activation in whole
      cells. They should label the active site of the corresponding caspase through a
      covalent attachment to the reactive cysteine residue. METHODS: One of the FLICAs,
      FAM-DEVD-fmk, was used to monitor apoptosis progression in leukemic JURL-MK1
      cells by means of flow cytometry. The effects of unlabeled caspase inhibitors z
      DEVD-fmk and z-VAD-fmk on FLICA staining were analyzed to evaluate the
      contribution of caspase-bound FLICA to the fluorescent signal. Covalent binding
      of inhibitors to caspase-3 subunit was revealed by Western blotting. RESULTS:
      Although the unlabeled inhibitors irreversibly bind to caspase-3, completely
      inhibit its activity, and prevent FLICA binding to caspase-3 even at
      concentrations lower than 5 muM, they have no effect on FLICA staining of
      apoptotic cells. CONCLUSIONS: Fluorescent signal of FLICA is characteristic for
      apoptotic cells but originates mainly from yet unspecified site(s) that differ
      from the caspase active site. This finding puts in doubt the specificity of
      staining by various FLICAs with regard to individual caspases and shows the need
      for an extreme care in the interpretation of data obtained using these labels.

PMID- 17549765
TI  - Quaternary benzo[c]phenanthridine alkaloids--novel cell permeant and red
      fluorescing DNA probes.
AB  - BACKGROUND: Quaternary benzo[c]phenanthridine alkaloids (QBAs) are naturally
      occurring compounds isolated from plants in the Fumariaceae, Papaveraceae,
      Ranunculaceae, and Rutaceae families. In addition to having a wide range of
      biological activities, they are also attractive for their fluorescent properties.
      We observed interesting fluorescent characteristics in the QBAs-macarpine (MA),
      sanguirubine (SR), chelirubine (CHR), sanguilutine (SL), chelilutine (CHL),
      sanguinarine (SA) and chelerythrine (CHE) after interaction with living cells.
      METHODS: Water stock solutions of the alkaloids (10-100 microg/ml) were added to
      intact cells, and after a brief incubation the cells were observed. Human cell
      lines HL60 (human promyelocytic leukemia), HeLa (human cervix adenocarcinoma),
      and LEP (human lung fibroblasts), and piglet blood were used in the experiments.
      Blood cells were stained with MA in combination with FITC-conjugated anti-CD45
      surface marker antibody. Cells were analyzed by fluorescence microscopy and by
      flow cytometry. RESULTS: All tested alkaloids immediately entered living cells
      with MA, CHR, and SA binding to DNA. MA showed the best DNA staining properties.
      Fluorescence microscopy of MA, CHR, and SA stained cells described the nuclear
      architecture and clearly described chromosomes and apoptotic fragments in living
      cells. Moreover MA can rapidly represent the cellular DNA content of living cells
      at a resolution adequate for cell cycle analysis. QBAs were excitable using
      common argon lasers (488 nm) emitting at a range of 575-755 nm (i.e. fluorescence
      detectors FL2-5). Spectral characteristics of MA allow simultaneous surface
      immunophenotyping. CONCLUSIONS: It was shown that MA, CHR, and SA stain nucleic
      acids in living cells. They can be used as supravital fluorescent DNA probes,
      both in fluorescence microscopy and flow cytometry, including multiparameter
      analysis of peripheral blood and bone marrow. MA binds DNA stochiometrically and
      can provide information on DNA content.

PMID- 17549766
TI  - Quality of life of children with neurological impairment who receive a
      fundoplication for gastroesophageal reflux disease.
AB  - BACKGROUND: Children with neurological impairment (NI) commonly have
      gastroesophageal reflux disease (GERD) treated with a fundoplication. The impact
      of this procedure on quality of life is poorly understood. OBJECTIVES: To examine
      the quality of life of children with NI who have received a fundoplication for
      GERD and of their caregivers. METHODS: The study was a prospective cohort study
      of children with NI and GERD who underwent a fundoplication at a children's
      hospital between January 1, 2005, and July 7, 2006. Quality of life of the
      children was assessed with the Child Health Questionnaire (CHQ) and of the
      caregivers with the Short-Form Health Survey Status (SF-36) and Parenting Stress
      Index (PSI), both at baseline and 1 month after fundoplication. Functional status
      was assessed using the WeeFIM. Repeated-measures analyses were performed.
      RESULTS: Forty-four of the 63 parents (70%) were enrolled. The median WeeFIM
      score was 31.2 versus the age-normal score of 83 (P = .001). Compared with the
      baseline scores, mean CHQ scores improved over 1 month in the domains of bodily
      pain (32.8 vs. 47.5, P = .01), role limitations-physical (30.6 vs. 56.6, P =
      .01), mental health (62.7 vs. 70.6, P = .01), family limitation of activities
      (43.3 vs. 55.1, P = .03), and parental time (43.0 vs. 55.3, P = .03). The
      parental SF-36 domain of vitality improved from baseline over 1 month (41.3 vs.
      48.2, P = .001), but there were no changes from baseline in Parenting Stress
      scores. CONCLUSIONS: Parents reported that the quality of life of children with
      NI who receive a fundoplication for GERD was improved from baseline in several
      domains 1 month after surgery. The quality of life and stress of caregivers did
      not improve in nearly all domains, at least in the short term.

PMID- 17549767
TI  - Iron-mediated degradation kinetics of substituted dispiro-1,2,4-trioxolane
      antimalarials.
AB  - The iron-mediated reactivity of various dispiro-1,2,4-trioxolanes was determined
      by automated kinetic analysis under standard reaction conditions. The active
      antimalarial compounds underwent peroxide bond cleavage by Fe(II) resulting in
      products indicative of carbon-centered radical formation. The rate of reaction
      was heavily influenced by the presence of spiro-substituted adamantane and
      cyclohexane rings, and was also significantly affected by cyclohexane ring
      substitution. Steric hindrance around the peroxide oxygen atoms appeared to be
      the major determinant of reaction rate, however polar substituents also affected
      reactivity by an independent mechanism. A wide range of reaction rates was
      observed within this class of peroxide antimalarials, however iron-mediated
      reactivity did not directly correlate with in vitro antimalarial activity.

PMID- 17549768
TI  - The development of heated tip force-distance measurements as a novel approach to
      site-specific characterization of pharmaceutical materials.
AB  - The study describes the development of a novel approach to surface analysis
      whereby thermal probes are used to perform scanning probe microscopy pull-off
      force measurements as a function of tip rather than sample temperature. The
      initial impetus for the investigation was the study of a poorly understood
      phenomenon associated with microthermal analysis (MTA) whereby the thermal probe
      is pulled into the surface of a sample following temperature-induced softening.
      Localized thermomechanical analysis experiments were performed on a range of
      pharmaceutical materials using TA Instruments 2990 Microthermal Analyzer equipped
      with a TM Microscopes Explorer atomic force microscope. The system was then
      interfaced with a second instrument to allow simultaneous probe temperature
      control and pull-off force measurement. It was found that the pull-in effect is
      due to the adhesion of the probe to the material at elevated (softening)
      temperatures. However, it was also noted that for paracetamol tablets the pull
      off force increased at temperatures well below the softening associated with
      melting. This behavior was ascribed to surface polymorphic changes caused by the
      compression process. The temperature-controlled pull-off force method therefore
      represents a novel and potentially widely applicable means of detecting surface
      changes that are not easily observed using isothermal pull-off force measurements
      or indeed standard MTA studies.

PMID- 17549769
TI  - Application of direct crystallization for racemic compound propranolol
      hydrochloride.
AB  - The application of direct crystallization integrating with chromatography to the
      resolution of a racemic compound propranolol hydrochloride was studied and the
      crystallization progression was clearly illustrated in terms of the diagram of
      solubility and metastable zone widths with different enantiomeric compositions.
      The solubility and metastable zone widths of propranolol hydrochloride in the
      mixture of methanol and isopropanol were determined using an in situ Lasentec
      Focused Beam Reflectance Measurement (FBRM) probe. The direct crystallizations
      were carried out in an automatic lab reactor (Mettler Toledo LabMax) system. The
      optical purity of final product crystals was examined using differential scanning
      calorimetry (DSC), HPLC and PXRD. The crystal size distribution and morphology
      were analyzed using Malvern Mastersizer and Jeol SEM. It was found that optically
      pure crystal product could be obtained within certain safe supersaturation limit
      and there was no evidence of polymorph or solvate/hydrate transformation during
      the crystallization process. There was no selectivity of crystal growth or
      nucleation between the pure enantiomer and its racemate when the solution reaches
      the temperature lower than saturation temperature of the racemate. Hence, the
      critical supersaturation control of a solution was essential to obtain pure
      enantiomers from a partially resolved racemate.

PMID- 17549770
TI  - Solid-state properties and relationship between anhydrate and monohydrate of
      baclofen.
AB  - Baclofen, a widely used antispastic agent, has been found to exist in two
      crystalline forms, the anhydrate and monohydrate. The aim of this study was (1)
      to identify and characterize these two solid phases of baclofen, and (2) to
      examine the processing-induced phase transformations associated with wet
      granulation of baclofen. Using multiple techniques (powder X-ray diffraction,
      thermal analysis, vibrational spectroscopy and water vapor sorption analysis), a
      structural relationship has been established between the anhydrate and
      monohydrate of baclofen. Thermal and variable-temperature powder X-ray
      diffraction data indicate that the monohydrate, which presumably belongs to the
      channel hydrate class, dehydrates at 60 degrees C with the formation of the
      anhydrate. Furthermore, the anhydrate to monohydrate transformation followed by
      optical microscopy was found to occur via a solvent-mediated route. During wet
      massing experiments, the critical moisture value for the hydrate formation under
      the conditions of the present study was identified using qualitative powder X-ray
      diffraction and Raman spectroscopy. Finally, the interconversion pathway between
      the two crystalline forms of baclofen was presented. The knowledge of this
      pathway provides better understanding and control of the solid state of baclofen
      during processing and storage.

PMID- 17549771
TI  - A qualitative method for monitoring of nucleation and granule growth in fluid bed
      wet granulation by reflectance near-infrared spectroscopy.
AB  - Potency and content uniformity of granulation and tablet samples are usually
      determined by HPLC or UV-VIS. However, these methods are not suitable for the
      determinations of other important process related attributes. The monitoring of
      nucleation, granule growth and granule breakage in the granulation process
      requires different analytical tools. In early formulation development of a new
      active pharmaceutical ingredient (API), out of trend content uniformity results
      were observed for batches manufactured using a fluid bed wet granulation process.
      A qualitative near infrared (NIR) method was used to characterize the process
      samples, which were separated into fractions with sieve sizes of 40, 60, 80, 100,
      and 200-mesh. Based on spectral analysis, the method was able to demonstrate
      changes in relative content of lactose, microcrystalline cellulose and the API at
      different processing times. The results also showed that the out of trend content
      uniformity was caused by large particle size of the API. Because lactose and
      microcrystalline cellulose are commonly used ingredients in wet granulation
      formulations, the qualitative NIR method may find wide applications.

PMID- 17549772
TI  - Preoperative cardiac risk stratification 2007: evolving evidence, evolving
      strategies.
AB  - Various guidelines and risk indices have optimized cardiac risk stratification,
      and the emphasis has shifted to reducing perioperative risk. This review is an
      update on invasive (CABG/PCI) and noninvasive (medical therapy with beta
      blockers, alpha-agonists, and statins) strategies to reduce cardiac risk for
      noncardiac surgery and the controversies surrounding their use.

PMID- 17549773
TI  - Firm-based trial to improve central venous catheter insertion practices.
AB  - BACKGROUND: Central venous catheters placed in femoral veins increase the risk of
      complications. At our institution, residents place most catheters in the femoral
      vein. OBJECTIVE: Determine whether a hands-on educational session reduced femoral
      venous catheterization and improved residents' confidence and adherence to
      recommendations for infection control. DESIGN: Firm-based clinical trial between
      November 2004 and March 2005. SETTING: General medical wards of Cook County
      (Stroger) Hospital (Chicago, IL), a public teaching hospital. PARTICIPANTS:
      Internal medicine residents (n = 150). INTERVENTION: Before their 4-week
      rotation, intervention-firm residents received a lecture and practiced placing
      catheters in mannequins; control-firm residents received the usual training.
      MEASUREMENTS: Venous insertion site, adherence to recommendations for infection
      control, knowledge and confidence about catheter insertion, and catheter
      associated complications RESULTS: Residents inserted 54 catheters, or 0.24
      insertions per resident per 4-week rotation. There was a nonsignificant decrease
      in femoral insertions for nondialysis catheters in the intervention group
      compared to the control group (44% vs. 58%), difference: -14% (95% CI, -52% to
      24%). The intervention significantly increased residents' knowledge of
      complications related to femoral vein catheterization and temporarily increased
      their confidence about placing internal jugular or subclavian venous catheters.
      Intervention-group residents were more likely to use masks during catheterization
      (risk ratio, 2.2; 95% CI, 1.3-2.7), but other practices were similar.
      CONCLUSIONS: Our intervention improved residents' knowledge of complications and
      use of masks during catheter insertion; however, it did not significantly change
      venous insertion sites. Catheter insertions on our general medicine wards are
      infrequent, and the skills acquired during the skills-building session may have
      deteriorated given the few clinical opportunities for reinforcement.

PMID- 17549774
TI  - Hospital quality measurement--perplexing for professionals, let alone for
      patients.

PMID- 17549775
TI  - Procedural training at a crossroads: striking a balance between education,
      patient safety, and quality.

PMID- 17549777
TI  - N,N,N-Trimethylchitosan chloride as a gene vector: synthesis and application.
AB  - N,N,N-Trimethylchitosan chloride with different degrees of quaternization has
      been synthesized and characterized by (1)H NMR spectroscopy. The particle size
      ranges from 150 to 600 nm, which is dependent on the N/P ratio and is less
      influenced by the degree of quaternization. The majority of the particles have a
      spherical morphology. The zeta potential of the particles increases with the N/P
      ratio and the quaternization degree of TMC. Short-term contact experiments show
      good biocompatibility of TMC, but long-term contact experiments reveal its high
      toxicity. This study suggests that TMC is a promising gene carrier, but further
      modification is still required to improve its cytocompatibility.

PMID- 17549778
TI  - 1H and 13C-NMR data of hydroxyflavone derivatives.
AB  - Many hydroxyflavone derivatives have been found in nature and shown to have many
      biological functions. Because their function is changed by the position and
      number of hydroxyl group, their structural identification is a fundamental and
      necessary step for understanding their functions. In the present study, the
      complete 1H and 13C NMR spectral assignments were presented for 6
      hydroxyflavones, and NMR data of additional 14 hydroxyflavone derivatives were
      compared with those of the 6 hydroxyflavones. In addition, the partially
      incorrect NMR data of two of the dihydroxyflavones whose NMR data were previously
      reported were corrected.

PMID- 17549779
TI  - Synthesis of doubly beta-to-beta 1,3-butadiyne-bridged diporphyrins: enforced
      planar structures and large two-photon absorption cross sections.

PMID- 17549780
TI  - A long research story culminates in the first total synthesis of moenomycin A.

PMID- 17549781
TI  - Trapping of oligomeric cyclopentadienyllithium cationic and anionic fragments by
      a V[triple bond]V-bonded ligand.

PMID- 17549782
TI  - Intramolecular [3+2] annulation of 5-Aryl-, 20-ethynyl-substituted
      [26]hexaphyrin(1.1.1.1.1.1) triggered by molecular compression through a dynamic
      conformational change.

PMID- 17549783
TI  - Double C--H activation of an N-heterocyclic carbene ligand in a ruthenium olefin
      metathesis catalyst.

PMID- 17549784
TI  - Small-molecule N-heterocyclic-carbene-containing olefin-metathesis catalysts for
      use in water.

PMID- 17549785
TI  - Ruthenium-catalyzed enantioselective propargylation of aromatic compounds with
      propargylic alcohols via allenylidene intermediates.

PMID- 17549786
TI  - A concise synthesis of enantioenriched fluorinated carbocycles.

PMID- 17549787
TI  - On the prebiotic synthesis of ribonucleotides: photoanomerisation of cytosine
      nucleosides and nucleotides revisited.
AB  - Recent work has emphasised the importance of D-ribose aminooxazoline 1 in the
      synthesis of cytidine ribonucleosides under potentially prebiotic conditions.
      Upon treatment with cyanoacetylene, 1 is transformed into alpha-D-cytidine (alpha
      2), and if an efficient means of anomerising this nucleoside or a derivative
      thereof were to be found, then the synthesis of one of the key beta-D-nucleosides
      required to make RNA would be realised. Photoanomerisation of alpha-2 has
      previously been described, but the yield was extremely low. Therefore, the
      present study was initiated to determine whether this low yield was the result of
      a low conversion or competing reaction pathways.

PMID- 17549788
TI  - The chemical composition of animal cells and their intracellular compartments
      reconstructed from 3D mass spectrometry.

PMID- 17549789
TI  - Structural, dynamic properties of key residues in Abeta amyloidogenesis:
      implications of an important role of nanosecond timescale dynamics.

PMID- 17549790
TI  - The Simpson-Golabi-Behmel syndrome causative glypican-3, binds to and inhibits
      the dipeptidyl peptidase activity of CD26.
AB  - Simpson-Golabi-Behmel syndrome (SGBS) is an X-linked condition shown to be the
      result of deletions of the glypican-3 (GPC3) gene. GPC3 is a proteoglycan
      localized to the cell membrane via a glycosylphosphatidyl-inositol (GPI) anchor.
      To further elucidate the GPC3 function(s), we have screened various cell lines
      for proteins that interact with GPC3, resulting in the isolation of a 115 kDa
      protein, identified as CD26. The interaction occurred with both the glycosylated
      and unglycosylated forms of GPC3 and led to the inhibition of CD26 peptidase
      activity. Moreover, introduction of CD26 into Cos-1 cells was accompanied by the
      up-regulation of cell growth, while inclusion of recombinant GPC3 in the media
      reduced the growth of CD26 transfected Cos-1 cells, drastically. Furthermore,
      HepG2 C3A cells containing CD26 underwent apoptosis in the presence of
      recombinant GPC3 in both concentration and time-dependant manner. In light of the
      fact that inhibition of CD26 reduces the rate of cell proliferation, we propose
      that a number of physical findings observed in SGBS patients may be a consequence
      of a direct interaction of GPC3 with CD26. Furthermore, GPC3 without the GPI
      anchor is capable of inducing apoptosis indicating that neither the GPI anchor
      nor the membrane attachment is required for apoptosis induction.

PMID- 17549791
TI  - A multivariate analysis approach to the integration of proteomic and gene
      expression data.
AB  - In order to understand even the simplest cellular processes, we need to integrate
      proteomic, gene expression and other biomolecular data. To date, most
      computational approaches aimed at integrating proteomics and gene expression data
      use direct gene/protein correlation measures. However, due to post
      transcriptional and translational regulations, the correspondence between the
      expression of a gene and its protein is complicated. We apply a multivariate
      statistical method, co-inertia analysis (CIA), to visualise gene and proteomic
      expression data stemming from the same biological samples. Principal components
      analysis or correspondence analysis can be used for data exploration on single
      datasets. CIA is then used to explore the relationships between two or more
      datasets. We further explore the data by projecting gene ontology (GO)
      information onto these plots to describe the cellular processes in action. We
      apply these techniques to gene expression and protein abundance data from studies
      of the human malarial parasite life cycle and the NCI-60 cancer cell lines. In
      each case, we visualise gene expression, protein abundance and GO classes in the
      same low dimensional projections and identify GO classes that are likely to be of
      biological importance.

PMID- 17549793
TI  - Subcellular proteomics of cell differentiation: quantitative analysis of the
      plasma membrane proteome of Caco-2 cells.
AB  - Human colorectal carcinoma (Caco-2) cells undergo in culture spontaneous
      enterocytic differentiation, characterized by polarization and appearance of the
      functional apical brush border membrane. To provide insights into the biology of
      differentiation, we have performed a comparative proteomic analysis of the plasma
      membranes from proliferating cells (PCs) and the apical membranes from
      differentiated cells (DCs). Proteins were resolved by SDS-PAGE, in-gel digested
      and analyzed by RP-LC and MS/MS. Alternatively, proteins were digested in
      solution, and tryptic peptides were labeled with isotopic tags and analyzed by 2
      D LC followed by MS/MS. Among the 1125 proteins identified in both proteomes, 76
      were found to be significantly increased in the membranes of DCs and 61 were
      increased in PCs. Majority of the proteins increased in the apical membranes were
      metabolic enzymes, proteins involved in the maintenance of cellular structure,
      transmembrane transporters, and proteins regulating vesicular transport. In
      contrast, majority of the proteins increased in the membranes of PCs were
      involved in gene expression, protein synthesis, and folding. Both groups
      contained many novel proteins with yet to be identified functions, which could
      provide potential new markers of the intestinal cells or of colorectal cancer.

PMID- 17549792
TI  - A protein chip approach for high-throughput antigen identification and
      characterization.
AB  - Proteomics research in humans and other eukaryotes demands a large number of high
      quality mAbs. Here, we report a new approach to produce high-quality mAbs against
      human liver proteins using a combined force of high-throughput mAb production and
      protein microarrays. After immunizing mice with live cells from human livers, we
      isolated 54 hybridomas with binding activities to human cells and identified the
      corresponding antigens for five mAbs via screening on a protein microarray of
      1058 unique human liver proteins. Finally, we demonstrated that using the five
      mAbs we could characterize the expression profiles of their corresponding
      antigens by using tissue microarrays. Among them, we discovered that eIF1A
      expressed only in normal liver tissues, not in hepatocellular carcinoma in
      humans.

PMID- 17549794
TI  - Broad spectrum identification of SUMO substrates in melanoma cells.
AB  - Like phosphorylation, protein sumoylation likely represents a dynamic PTM to
      alter protein function in support of cell regulatory systems. The broad-spectrum
      impact of transient or chronic engagement of signal transduction cascades on
      protein sumoylation has not been explored. Here, we find that epidermal growth
      factor (EGF) stimulation evokes a rapid alteration in small ubiquitin modifier
      (SUMO) target selection, while oncogene expression alters steady-state SUMO
      protein profiles. A proteomic SUMO target analysis in melanoma cells identified
      proteins involved in cellular signaling, growth control, and neural
      differentiation.

PMID- 17549795
TI  - Functional proteomic view of metabolic regulation in "Aromatoleum aromaticum"
      strain EbN1.
AB  - The denitrifying "Aromatoleum aromaticum" strain EbN1 utilizes a wide range of
      aromatic and nonaromatic compounds under anoxic and oxic conditions. The recently
      determined genome revealed corresponding degradation pathways and predicted a
      fine-tuned regulatory network. In this study, differential proteomics (2-D DIGE
      and MS) was used to define degradation pathway-specific subproteomes and to
      determine their growth condition dependent regulation. Differential protein
      profiles were determined for cultures adapted to growth under 22 different
      substrate and redox conditions. In total, 354 different proteins were identified,
      199 of which displayed significantly changed abundances. These regulated proteins
      mainly represented enzymes of the different degradation pathways, and revealed
      different degrees of growth condition specific regulation. In case of three
      substrate conditions (e.g. phenylalanine, anoxic), proteins previously predicted
      to be involved in their degradation were apparently not involved (e.g. Pdh,
      phenylacetaldehyde dehydrogenase). Instead, previously not considered proteins
      were specifically increased in abundance (e.g. EbA5005, predicted
      aldehyde:ferredoxin oxidoreductase), shedding new light on the respective
      pathways. Moreover, strong evidence was obtained for thus far unpredicted
      degradation pathways of three hitherto unknown substrates (e.g. o-aminobenzoate,
      anoxic). Comparing all identified regulated and nonregulated proteins provided
      first insights into regulatory hierarchies of special degradation pathways versus
      general metabolism in strain EbN1.

PMID- 17549796
TI  - Proteome analysis of the Atlantic salmon (Salmo salar) cell line SHK-1 following
      recombinant IFN-gamma stimulation.
AB  - Type II IFN exists as a single molecule (IFN-gamma) in contrast to type I IFN, of
      which there are a number of different forms. IFN-gamma is involved both directly
      and indirectly in antiviral activity, stimulation of bactericidal activity,
      antigen presentation and activation of macrophages. Recently IFN-gamma was cloned
      from a salmonid fish, the rainbow trout and a functional recombinant protein
      produced exhibited IFN-gamma activity. This recombinant IFN-gamma was used to
      stimulate an Atlantic salmon cell line, SHK-1, to monitor the changes in protein
      expression by proteomic analysis 24 h after stimulation compared to unstimulated
      control cells. An SHK-1 cell proteome map was developed and proteins altered in
      abundance by the IFN-gamma stimulation were identified. Under the analytical
      conditions used, 22 proteins were found to be altered in abundance, 15 increased
      and 7 decreased. Several proteins were excised from the gel and identified,
      following trypsin digestion and MALDI-MS/MS/LC-MS and database interrogation.
      Transcriptional analysis of five mRNAs encoding proteins increased in abundance
      by IFN-gamma in the proteome analysis was determined by real-time PCR. We
      assessed the correlation between gene expression and change in abundance of
      proteins for these genes.

PMID- 17549797
TI  - Proteome analysis of the rat hepatic stellate cells under high concentrations of
      glucose.
AB  - To study the change in hepatic stellate cell (HSC) function under diabetic
      conditions, we cultured rat HSC in the presence of 5 and 30 mM glucose, which
      correspond to blood glucose concentrations during the early and late stages of
      diabetes, respectively. The differentially expressed HSC proteins were analyzed
      using 2-DE and ESI-Q-TOF MS/MS and confirmed with Western blotting. The changed
      protein expression will provide greater understanding of glycolysis in HSC at the
      high concentration of glucose.

PMID- 17549798
TI  - Analysis of modified apolipoprotein B-100 structures formed in oxidized low
      density lipoprotein using LC-MS/MS.
AB  - Oxidatively modified low-density lipoprotein (oxLDL) is one of the major factors
      involved in the development of atherosclerosis. Because of the insolubility of
      apolipoprotein B-100 (apoB-100) and the heterogeneous nature of oxidative
      modification, modified structures of apoB-100 in oxLDL are poorly understood. We
      applied an on-Membrane sample preparation procedure for LC-MS/MS analysis of apoB
      100 proteins in native and modified low-density lipoprotein (LDL) samples to
      eliminate lipid components in the LDLs followed by collection of tryptic digests
      of apoB-100. Compared with a commonly used in-gel digestion protocol, the sample
      preparation procedure using PVDF membrane greatly increased the recovery of
      tryptic peptides and resulted in improved sequence coverage in the final
      analysis, which lead to the identification of modified amino acid residues in
      copper-induced oxLDL. A histidine residue modified by 4-hydroxynonenal, a major
      lipid peroxidation product, as well as oxidized histidine and tryptophan residues
      were detected. LC-MS/MS in combination with the on-Membrane sample preparation
      procedure is a useful method to analyze highly hydrophobic proteins such as apoB
      100.

PMID- 17549799
TI  - A high-throughput strategy for protein profiling in cell microarrays using
      automated image analysis.
AB  - Advances in antibody production render a growing supply of affinity reagents for
      immunohistochemistry (IHC), and tissue microarray (TMA) technologies facilitate
      simultaneous analysis of protein expression in a multitude of tissues. However,
      collecting validated IHC data remains a bottleneck problem, as the standard
      method is manual microscopical analysis. Here we present a high-throughput
      strategy combining IHC on a recently developed cell microarray with a novel,
      automated image-analysis application (TMAx). The software was evaluated on 200
      digital images of IHC-stained cell spots, by comparing TMAx annotation with
      manual annotation performed by seven human experts. A high concordance between
      automated and manual annotation of staining intensity and fraction of IHC
      positive cells was found. In a limited study, we also investigated the
      possibility to assess the correlation between mRNA and protein levels, by using
      TMAx output results for relative protein quantification and quantitative real
      time PCR for the quantification of corresponding transcript levels. In
      conclusion, automated analysis of immunohistochemically stained in vitro-cultured
      cells in a microarray format can be used for high-throughput protein profiling,
      and extraction of RNA from the same cell lines provides a basis for comparing
      transcription and protein expression on a global scale.

PMID- 17549800
TI  - Helicobacter pylori polyclonally activates murine CD4(+) T cells in the absence
      of antigen-presenting cells.
AB  - Helicobacter pylori is a Gram-negative bacterium that causes a variety of
      gastrointestinal diseases, such as duodenal ulcer and gastric carcinoma. The T
      cell response against H. pylori is thought to contribute to the pathogenesis of
      these diseases. Here, we show that mouse-adapted H. pylori is able to
      polyclonally activate murine CD4(+) T lymphocytes, irrespective of their antigen
      specificity. Murine T helper cell clones as well as short-term cultured,
      polyclonal Th1 and Th2 cell lines and a human T cell clone, but not naive CD4(+)
      T cells, could be activated in this manner. The effect was independent of antigen
      presenting cells and required direct contact between H. pylori and T cells. Only
      whole cells of H. pylori, but not lysates or sonicates were able to activate T
      cells. The activity was lost after long-term culture of H. pylori on agar-plates.
      Degradation of H. pylori proteins with specific peptidases dramatically reduced
      the stimulating ability, implicating that the responsible molecule is likely to
      be a protein. This unexpected polyclonal T cell stimulatory mechanism may
      contribute to the T cell-mediated pathogenicity characteristic for H. pylori
      mediated diseases.

PMID- 17549801
TI  - Association between physical activity and quality of life among Western
      Australian breast cancer survivors.
AB  - Previous research has shown that physical activity (PA) may be beneficial to
      quality of life (QoL) in breast cancer survivors. Few studies however, have
      focused on the time period soon after the completion of adjuvant therapy or
      examined exercise issues separately for rural/urban or healthy weight/obese
      breast cancer survivors. Our study addressed these issues. Breast cancer
      survivors (N = 558) from the Western Australia Cancer Registry completed a survey
      that included the Godin Leisure Time Exercise Questionnaire (GLTEQ) and the
      Functional Assessment of Cancer Therapy-Breast (FACT-B) scale. Results showed
      that only 31% of breast cancer survivors were meeting the recommended PA
      guidelines post-treatment. Analysis of variance revealed that survivors meeting
      these guidelines reported higher scores on the FACT-B (mean difference 8.6; 95%
      CI = 5.0-12.1; p<0.001), the FACT-General (mean difference 6.3; 95% CI = 3.5-9.0;
      p<0.001), the trial outcome index (TOI; p<0.001), and several of the FACT-B
      subscales. Furthermore, healthy weight participants also reported higher scores
      than obese participants on the FACT-B (p = 0.058) and the breast cancer subscale
      (p = 0.033). There were no differences based on geographic location. We conclude
      that physically active and healthy weight breast cancer survivors report better
      QoL than their inactive and obese counterparts soon after completing adjuvant
      therapy.

PMID- 17549802
TI  - Psychiatric morbidity and quality of life in wives of men with long-term head and
      neck cancer.
AB  - The diagnosis of cancer not only affects the lives of patients but also the lives
      of their relatives. The aim of this study was to investigate the prevalence of
      psychiatric disorders and quality of life (QoL) among wives of patients treated
      for head and neck cancer (HNC). We examined 31 wives of patients treated for HNC
      from January 1998 to December 2004 (meantime since diagnosis 3.7 years) by
      questionnaires with regard to quality of life (WHOQOL-BREF), quality of the
      relationship (Dyadic Adjustment Scale), and affective symptoms (Hospital Anxiety
      and Depression Scale, HADS). Prevalence of psychiatric morbidity was measured by
      the Mini International Neuropsychiatric Interview (MINI). Results indicated that
      QoL and satisfaction with the relationship were comparable to the normal
      population. HADS mean scores showed no clinically relevant levels of depression
      and anxiety. A high prevalence of psychiatric disorders (38.7%, particularly
      agoraphobia) was found in the MINI. Wives diagnosed with an anxiety disorder
      reported significantly lower QoL compared to those without. The results of this
      study suggest that agoraphobia is a frequent psychiatric disorder seen in wives
      of HNC patients. Diagnosis of HNC can have a strong impact on the mental health
      of the spouse and should be taken in account in counselling of HNC patients.

PMID- 17549803
TI  - Patient employment status and satisfaction following cochlear implantation.
AB  - The aim of this study was to look at the effect on employment and employee
      perception of career opportunities after receiving a cochlear implant.
      Retrospective analysis based on a patient questionnaire was conducted. Eighty
      patients were identified: 65 (81.3%) participated in the questionnaire. Forty
      five patients (69.2%) were working prior to implant compared to 54 (83.9%) after
      implant. Job satisfaction rating rose from 5.56 to 6.82 following cochlear
      implantation. Twenty patients (30.8%) were unemployed prior to surgery while 11
      (16.9%) remained unemployed post implantation. Twenty-six patients (57.7%) from
      the working group believed that their hearing disability had affected their
      career, while 18 (40%) from the same group believed that receiving the cochlear
      implant significantly improved their career prospects. Cochlear implantation is
      associated with an improved chance of being employed. It also helps with improved
      job satisfaction as well as improving employee perception of their career
      prospects.

PMID- 17549804
TI  - A preliminary study looking at parental emotions following cochlear implantation.
AB  - This preliminary research investigated the emotions of parents with cochlear
      implanted children. The object for the research was first to compare four
      emotions engendered in parents of deaf children before and after cochlear
      implantation. Second, to monitor changes in these emotions during a period of up
      to four years after implantation. Third, to see whether any of the emotions
      studied was significantly more prominent than the others, and fifth to identify
      any differences in emotions that were related to the gender of parents. A self
      report questionnaire was given to 112 participants of whom 53 replied. There were
      equal groups of parents in two categories, those with children up to two years
      after implantation, and those two to four years after implantation. The responses
      were interpreted using parametric statistics. The results highlight that grief is
      the strongest emotional condition that parents experience before and up to two
      years after implantation, alongside family adjustments. Parents of the up to two
      years after implantation group generally have stronger feelings and are less
      satisfied than parents in the over two years implanted group. Finally, fathers
      use denial more than mothers. Considerations for future research and implications
      for paediatric cochlear implant teams will be discussed.

PMID- 17549805
TI  - The Great Ormond Street Hospital paediatric cochlear implant programme 1992-2004.
      A review of surgical complications.
AB  - The authors present a review of surgical complications following cochlear
      implantation at Great Ormond Street Hospital, since inception of the programme in
      1992 until June 2004. Complications are defined as major (resulting in re
      operation, explantation, re-implantation or which resulted in permanent serious
      morbidity or mortality) or minor (where the implant was not threatened). A
      comparison of surgical complication rates is made both with an earlier study in
      the same institution and also with other cochlear implantation centres worldwide.
      The decrease in surgical complication rates is discussed along with the
      difficulties inherent in cochlear implantation in the paediatric population with
      coexisting medical complaints.

PMID- 17549806
TI  - Cochlear implantation in a patient with Perisylvian syndrome.
AB  - Perisylvian syndrome is a rare neurological disorder characterised by the partial
      paralysis of muscles, epilepsy and mild to severe mental retardation. It is
      associated with hearing loss and delay in language and speech development. This
      presents additional challenges in the assessment of whether a child is suitable
      for cochlea implantation. The method to determine whether the hearing loss is of
      cochlear or central origin and the progress of a child with Perisylvian syndrome
      who received a cochlear implant is discussed.

PMID- 17549807
TI  - Childhood Development after Cochlear Implantation (CDaCI) study: design and
      baseline characteristics.
AB  - Children with severe to profound sensorineural hearing loss face communication
      challenges that influence language, psychosocial and scholastic performance.
      Clinical studies over the past 20 years have supported wider application of
      cochlear implants in children. The Childhood Development after Cochlear
      Implantation (CDaCI) study is the first longitudinal multicentre, national cohort
      study to evaluate systematically early cochlear implant (CI) outcomes in
      children. The objective of the study was to compare children who have undergone
      cochlear implantation, with similarly aged hearing peers across multiple domains,
      including oral language development, auditory performance, psychosocial and
      behavioural functioning, and quality of life. The CDaCI study is a multicentre
      national cohort study of CI children and normal hearing (NH) peers. Eligibility
      criteria include informed consent, age less than 5 years, pre- or post-lingually
      deaf, developmental criteria met, commitment to educate the child in English and
      bilateral cochlear implants. All children had a standardised baseline assessment
      that included demographics, hearing and medical history, communication history,
      language measures, cognitive tests, speech recognition, an audiological exam,
      psychosocial assessment including parent-child videotapes and parent reported
      quality of life. Follow-up visits are scheduled at six-month intervals and
      include a standardised assessment of the full battery of measures. Quality
      assurance activities were incorporated into the design of the study. A total of
      188 CI children and 97 NH peers were enrolled between November 2002 and December
      2004. The mean age, gender and race of the CI and NH children are comparable.
      With regard to parental demographics, the CI and NH children's families are
      statistically different. The parents of CI children are younger, and not as well
      educated, with 49% of CI parents reporting college graduation vs. 84% of the NH
      parents. The income of the CI parents is also lower than the NH parents.
      Assessments of cognition suggest that there may be baseline differences between
      the CI and NH children; however the scores were high enough to suggest language
      learning potential. The observed group differences identified these baseline
      characteristics as potential confounders which may require adjustment in analyses
      of outcomes. This longitudinal cohort study addresses questions related to high
      variability in language outcomes. Identifying sources of that variance requires
      research designs that: characterise potential predictors with accuracy, use
      samples that adequately power a study, and employ controls and approaches to
      analysis that limit bias and error. The CDaCI study was designed to generate a
      more complete picture of the interactive processes of language learning after
      implantation.

PMID- 17549808
TI  - The global challenge.

PMID- 17549809
TI  - All things being equal.

PMID- 17549810
TI  - More data on maraviroc in treatment-experienced patients.

PMID- 17549811
TI  - Entecavir results in undetectable HBV in patients restarting treatment.

PMID- 17549812
TI  - Cross-protection data for Gardasil submitted to FDA.

PMID- 17549813
TI  - [A 58.year old woman with short bowel syndrome and nutrition failure].

PMID- 17549814
TI  - [Short bowel and nutrition failure].

PMID- 17549815
TI  - Ethnic war leaves Burundi's health sector in ruins.

PMID- 17549816
TI  - Developing countries court medical tourists.

PMID- 17549817
TI  - Living with loss.

PMID- 17549818
TI  - Point:Counterpoint "Release of an endothelium-derived vasoconstrictor and
      RhoA/Rho kinase-mediated calcium sensitization of smooth muscle cell contraction
      are/are not the main effectors for full and sustained hypoxic pulmonary
      vasoconstriction".

PMID- 17549819
TI  - Point:Counterpoint "Release of an endothelium-derived vasoconstrictor and
      RhoA/Rho kinase-mediated calcium sensitization of smooth muscle cell contraction
      are/are not the main effectors for full and sustained hypoxic pulmonary
      vasoconstriction".

PMID- 17549820
TI  - Point:Counterpoint "Release of an endothelium-derived vasoconstrictor and
      RhoA/Rho kinase-mediated calcium sensitization of smooth muscle cell contraction
      are/are not the main effectors for full and sustained hypoxic pulmonary
      vasoconstriction".

PMID- 17549821
TI  - Point:Counterpoint "Release of an endothelium-derived vasoconstrictor and
      RhoA/Rho kinase-mediated calcium sensitization of smooth muscle cell contraction
      are/are not the main effectors for full and sustained hypoxic pulmonary
      vasoconstriction".

PMID- 17549822
TI  - Comprehensive mathematical modeling in drug addiction sciences.
AB  - The science of mathematical modeling aims to describe and evaluate complex
      phenomena. In epidemiology, modeling allows scientists to simulate the
      consequences of various intervention and prevention scenarios. In biology,
      modeling allows one to describe and simulate complex neurophysiologic processes.
      Similar modeling techniques apply to both scenarios. At the 2006 College on
      Problems of Drug Dependence (CPDD) workshop, we presented four types of models:
      traditional epidemiologic, traditional neurobiological/behavioral, knowledge
      repository epidemiologic, and knowledge repository neurological/behavioral. We
      discussed commonality and differences in the approaches, interpretations,
      utility, and limitations. The authors believe that both traditional and knowledge
      repository models can be very useful in complementary ways to the general
      scientific community studying substance abuse.

PMID- 17549823
TI  - Erectile dysfunction: a sentinel marker for cardiovascular disease in primary
      care.
AB  - Erectile dysfunction (ED) is a common, age-related disorder that diminishes
      quality of life for affected men and their partners. While most ED is now
      recognized as organic in origin, both organic and psychogenic causes often
      conspire to reduce sexual function in men with ED. Vasculopathy has come to be
      recognized as the most common cause of ED, which has elevated ED's importance in
      the primary care setting as a sentinel to underlying cardiovascular disease.
      Identification of cardiovascular risk factors should be a routine part of the
      evaluation for ED and is as important as taking the patient's sexual, medication,
      and psychosocial histories. Involving the patient's partner in evaluation and
      management is often valuable. Treatment with phosphodiesterase type 5 inhibitors
      is effective in restoring sexual function for most men with ED, but patients and
      their partners should be encouraged to make an informed choice from among all
      available treatment options.

PMID- 17549824
TI  - Evolving issues in male hypogonadism: evaluation, management, and related
      comorbidities.
AB  - Hypogonadism in men has a complex and varied pathogenesis. In addition to
      multiple established causes of the disease, low testosterone levels are
      associated with various comorbidities, including metabolic syndrome and type 2
      diabetes. Symptoms associated with hypogonadism include reduced sex drive,
      fatigue, and mood disturbances, but accurate diagnosis requires biochemical
      testing. Total testosterone is considered the appropriate testosterone
      measurement in most situations in primary care, although free testosterone is a
      more accurate marker and is indicated in some situations. Testosterone
      replacement therapy is a valid treatment option for men with testosterone
      deficiency accompanied by symptoms of hypogonadism. The goals of therapy are to
      restore physiologic testosterone levels and alleviate symptoms. A potential
      association of testosterone replacement therapy with prostate cancer is the
      biggest safety concern, so patient monitoring should include regular digital
      rectal examination and prostate-specific antigen tests.

PMID- 17549825
TI  - Prostatitis: Infection, neuromuscular disorder, or pain syndrome? Proper patient
      classification is key.
AB  - Prostatitis is a broad term used to describe inflammation of the prostate that
      may be associated with a myriad of lower urinary tract symptoms and symptoms of
      sexual discomfort and dysfunction. The condition affects 5% to 10% of the male
      population and is the most common urologic diagnosis in men younger than 50
      years. Prostatitis is classified into four categories, including acute and
      chronic bacterial forms, a chronic abacterial form, and an asymptomatic form. The
      bacterial forms are more readily recognized and treated, but symptoms in most
      affected men are not found to have an infectious cause. Indeed, chronic
      abacterial prostatitis (also known as chronic pelvic pain syndrome) is both the
      most prevalent form and also the least understood and the most challenging to
      evaluate and treat. This form of prostatitis may respond to non-prostate-centered
      treatment strategies such as physical therapy, myofascial trigger point release,
      and relaxation techniques. Because the various forms of prostatitis call for
      vastly different treatment approaches, appropriate evaluation, testing, and
      differential diagnosis are crucial to effective management.

PMID- 17549826
TI  - Pathway clarity.

PMID- 17549827
TI  - Devising an assessment tool.

PMID- 17549829
TI  - One hospital's answer to the nursing shortage.

PMID- 17549830
TI  - Lessons from  primary HIV infection.

PMID- 17549831
TI  - Acute infection: client and provider challenges.

PMID- 17549832
TI  - Expanding access to syringes.

PMID- 17549833
TI  - More than clean needles: overdose prevention and syringe exchange.

PMID- 17549834
TI  - Funding. U.S. cuts off payments to Puerto Rico clinics.

PMID- 17549835
TI  - New Jersey pushes for HIV testing of pregnant women.

PMID- 17549836
TI  - Denial of SSI benefits for HIV-positive applicant remanded.

PMID- 17549837
TI  - Reporting. CDC: all HIV patients to be tracked by name by year's end.

PMID- 17549838
TI  - HIV and TB. HIV a primary focus on World Tuberculosis Day.

PMID- 17549839
TI  - HIV-positive man's claim for inadequate care dismissed.

PMID- 17549840
TI  - Exposure. Pimp's violation of interstate-commerce conviction affirmed.

PMID- 17549841
TI  - Prisons. HIV-positive inmate must pay filing fee to proceed with claim.

PMID- 17549842
TI  - Partnership reaches U.S. women at high risk for HIV/AIDS.

PMID- 17549843
TI  - Re: Canadian Cardiovascular Society position statement--recommendations for the
      diagnosis and treatment of dyslipidemia and prevention of cardiovascular disease.

PMID- 17549844
TI  - Physician payment: is there a better way to pay?

PMID- 17549845
TI  - Falls, disability and food insecurity present challenges to healthy aging.

PMID- 17549846
TI  - Mechanisms of drug action and drug resistance in Leishmania as basis for
      therapeutic target identification and design of antileishmanial modulators.

PMID- 17549847
TI  - What have you done for me lately? Assessing hospital community benefit.
AB  - This issue brief reviews key aspects of the ongoing policy debate related to not
      for-profit hospitals, the advantages they derive from tax exemption, and the
      benefits they provide to communities served. It provides a historical context for
      how federal standards for assessing hospitals' tax-exempt status have evolved and
      describes recent activities to explore additional policy changes. Legislative and
      regulatory actions at the state and local level are also examined. Evidence on
      the performance of not-for-profit hospitals in comparison to their for-profit
      competitors on measures of cost, quality, and access is summarized, and
      perspectives on the need to preserve a not-for-profit presence in health care are
      explored. Efforts to develop standardized metrics for measuring community benefit
      are described, and alternative conventions for reporting charity care
      contributions are discussed.

PMID- 17549848
TI  - Nicholson creates new team to lead 'third stage of reform'.

PMID- 17549849
TI  - BMA sets out plan to close purchaser-provider divide.

PMID- 17549851
TI  - Imperial leads merger on hunt for joined-up research.

PMID- 17549850
TI  - Emergency czar backs A&E closure.

PMID- 17549852
TI  - On payment by results.

PMID- 17549853
TI  - Blair's legacy. 1997 and all that: Blair remembered.

PMID- 17549854
TI  - Data briefing. Steady progress for acute productivity.

PMID- 17549855
TI  - Well-being. In pursuit of happiness.
AB  - The previously neglected performance measure of 'satisfaction' is now being
      gauged by government. A new centre set up by the Office for National Statistics
      is measuring whether activity leads to improved quality. A raft of theorisis
      suggest that happiness is as key to good health as more clinical interventions.

PMID- 17549856
TI  - Sustainability. Fuelling health.

PMID- 17549857
TI  - Winning the ward war.

PMID- 17549858
TI  - A history of Oxford unicompartmental knee arthroplasty.

PMID- 17549859
TI  - Oxford unicompartmental knee replacement: literature review.
AB  - Oxford unicompartmental knee replacement surgery (Biomet Orthopedics, Inc,
      Warsaw, Ind) provides excellent long-term results according to numerous published
      series, with 10-year survivorship ranging from 91% to 100% and 15- year
      survivorship of 93%. Few knee prostheses can rival these results. Most of these
      cohorts included patients with anteromedial- or medial-specific disease, although
      some cohorts included patients with lateral-specific disease. Also, most cohorts
      were performed in patients with a mean age of >60 years, with a wide range of
      ages including patients in their 30s to 90s. Almost all of the arthroplasties
      were performed in patients with osteoarthritis, and some were performed in
      patients with avascular necrosis.

PMID- 17549860
TI  - A prospective analysis of Oxford phase 3 unicompartmental knee arthroplasty.
AB  - We performed 560 minimally invasive unicompartmental knee arthroplasties in
      patients with osteoarthritis using the Oxford phase 3 prosthesis since January
      2002. For the prospective analysis, clinical and radiographic assessments were
      carried out preoperatively and regularly followed after surgery. Ninety-five
      cases were followed at 3, 6, 12, 24, and 36 months postoperatively. In this
      prospective study, the early postoperative results of minimally invasive Oxford
      phase 3 unicompartmental knee arthroplasty were satisfactory for improvement of
      knee score and function score of the American Knee Society (AKS) score, and
      recovery of knee motion. The AKS knee score and function score continued to
      improve for 3 years postoperatively.

PMID- 17549861
TI  - Obesity, young age, patellofemoral disease, and anterior knee pain: identifying
      the unicondylar arthroplasty patient in the United States.
AB  - Standard surgical criteria for unicondylar knee arthroplasty exclude patients who
      weigh >82 kg (187 lbs), patients aged <60 years, and patients with more than
      minimal erosive changes in the patellofemoral articulation, indicated clinically
      by anterior knee pain. In April 2004, the US Food and Drug Administration
      approved the Oxford phase 3 unicondylar prosthesis for implantation during
      unicompartmental knee arthroplasty. Since this broader indication was adopted,
      the implant has proven to be a bone- and ligament- conservative yet long-lasting
      intervention for anteromedial arthritis of the knee. The purpose of this study is
      to investigate the early outcomes of unicompartmental medial knee arthroplasty
      using the Oxford prosthesis in US patients who do not meet the standard inclusion
      criteria. Specifically, the current study investigates the impact of obesity,
      young age, patellofemoral arthritis, and isolated medial knee pain on the early
      outcomes of this device. In this large series of 318 unicompartmental knee
      arthroplasties performed in 270 patients, these standard preoperative
      contraindications had no influence on the successful outcome of the procedure
      using the Oxford phase 3 device.

PMID- 17549862
TI  - Radiolucency and migration after Oxford unicompartmental knee arthroplasty.
AB  - Radiolucent lines frequently appear on radiographs around unicompartmental knee
      arthroplasties. It is unknown why this occurs, although the lines usually appear
      during the first year following the procedure. Knee arthroplasty implants are
      also known to migrate during the first year. Considering the similarity in the
      timing of appearance of radiolucency and implant migration, it seems that they
      could be related. The aim of this study was to determine whether there is a
      correlation between presence of radiolucency and the migration of Oxford
      unicompartmental knee arthroplasty implants.

PMID- 17549863
TI  - Medial tibial plateau fracture and the Oxford unicompartmental knee.
AB  - Tibial plateau fracture is a rare complication of unicompartmental knee
      arthroplasty. The fracture almost always occurs during surgery, and it is likely
      to be the result of a technical error, usually an unnecessarily deep vertical saw
      cut into the proximal tibia. However, anything that weakens or overloads the
      proximal tibia may contribute to fracture, such as damage to the posterior
      cortex, excess removal of bone particularly in small patients with osteopenic
      bones, inadequate preparation of the keel slot, or use of excessive force with a
      heavy hammer. This series of eight case reports presents our experience with this
      complication after medial Oxford unicompartmental knee arthroplasty and outlines
      a treatment protocol.

PMID- 17549864
TI  - Preoperative and postoperative limb alignment after Oxford unicompartmental knee
      arthroplasty.
AB  - From a series of 64 sequential Oxford (Biomet Orthopedics, Inc, Warsaw, phase 3
      implants, two study groups were selected: 23 knees with unilateral surgery and a
      normal opposite side, and 21 knees with bilateral simultaneous surgery. Standing
      3-foot radiographs were taken pre- and postoperatively to assess the femorotibial
      angle and the location of the mechanical axis of the limb in relation to the
      knee. Results in the unilateral group showed an average postoperative
      femorotibial angle of 4.50 was compared to a 3.40 angle for the normal side, (not
      significantly different; P=.09). Results for the bilateral group were an average
      postoperative femorotibial angle of 3.40 for the right and 3.50 for the left,
      (not significantly different; P=.7). The location of the mechanical axis was
      similar between the knees in both groups. The study concludes that the Oxford
      soft-tissue balancing technique restores alignment, which is on average similar
      to the opposite side, and therefore presumably normal for that knee. Restoration
      of normal alignment should not put excess stress onto the lateral compartment.

PMID- 17549865
TI  - Surface stress: a factor influencing ultra high molecular weight polyethylene
      durability in mobile-bearing knee design.
AB  - The continuing global interest in the use of total and unicompartmental mobile
      bearing knee designs is manifest by an appreciation of their clinical
      performance. Like their fixed plateau counterparts, mobile-bearing knees are
      influenced by patient and surgical variables as well as design, material, and
      manufacturing choices. This article is a focused description of tibiofemoral
      surface stress distributions, as a predictor of in vivo material durability for
      three contemporary designs at positions encountered during daily activity.

PMID- 17549866
TI  - Combined anterior cruciate ligament reconstruction and unicompartmental knee
      arthroplasty: surgical technique.
AB  - Anterior cruciate ligament (ACL) reconstruction can be safely combined with
      medial unicompartmental knee arthroplasty from a technical point of view. The
      procedure has been performed in younger patients with the goal of preserving bone
      in case of need for future revision. The short-term results are encouraging
      although longer-term data are necessary to thoroughly evaluate the role of this
      procedure in patients with medial compartment osteoarthritis and ACL deficiency.

PMID- 17549867
TI  - Bearing movement after Oxford unicompartmental knee arthroplasty: a mathematical
      model.
AB  - Movements of the meniscal bearing on the tibial plateau after Oxford knee
      arthroplasty (Biomet Orthopedics, Inc, Warsaw, Ind) reflect tibiofemoral
      movement. They have been shown to be load dependent. This article describes the
      use of a mathematical model of the knee in the sagittal plane to show that
      movement differences under load are caused by differences in ligament strains
      induced by different combinations of external loads and muscle forces. During
      passive flexion, roll-back of the femur on the tibia is required to minimize the
      forces transmitted by the ligaments.

PMID- 17549868
TI  - The incidence and prevention of symptomatic thromboembolic disease following
      unicompartmental knee arthroplasty.
AB  - Deep venous thrombosis (DVT) and pulmonary embolism (PE) are significant concerns
      following lower extremity arthroplasty. Many prevention protocols exist. This
      study investigates the rate of venous thromboembolic disease (DVT and PE) in 423
      patients undergoing consecutive unicompartmental knee arthroplasties by two
      surgeons (A.V.L., K.R.B.) using a multimodal prophylactic strategy. Risk
      stratification by the medical consulting team determined appropriate
      anticoagulation level. Eighty-two percent (knees) were managed with an aspirin
      based program, 8% with 2 weeks of low molecular weight heparin followed by
      aspirin, and 8% with warfarin. No patient experienced symptomatic DVT or PE.
      Radiographic investigations revealed no asymptomatic venous thromboembolic
      disease. A risk stratification and multimodal venous thromboembolic disease
      prevention program based on the efficacy and safety of aspirin may prove to be
      the safest, most effective method in patients undergoing unicompartmental knee
      arthroplasty. The minimally invasive nature and rapid recovery associated with
      unicompartmental knee arthroplasty may support approaching the procedure more as
      an arthroscopy than an arthroplasty in terms of venous thromboembolic disease
      prevention.

PMID- 17549869
TI  - Tumour necrosis factor-alpha as a new therapeutic target for rheumatoid
      arthritis: an update.
AB  - In rheumatoid arthritis (RA), the conventional therapies (first-line, second
      line, third-line drugs) provide more or less effective symptomatic relief for a
      decade or so from the onset of the disease. However, the chronic inflammatory
      destructive processes involving connective tissue, cartilage and bone with their
      attendant disability progress relentlessly in majority of patients. Secondly, use
      of 'second-line' and 'third-line' drugs in RA are limited due to their side
      effects. Studies in animals and RA patients have confirmed that tumour necrosis
      factor-alpha (TNFalpha), an inflammatory cytokine, is of major importance in the
      rheumatoid disease process and thus, it might be an effective therapeutic target
      in RA. Animal model experiments and clinical trials were conducted with anti
      TNFalpha monoclonal antibody (anti-TNFalpha MoAb) in RA recently. This anti
      TNFalpha MoAb therapy was found to be both effective and safe which documented
      the coming-of-age of cytokine-based immunointervention in RA. Researchers are
      optimistic that modern medicine would certainly witness the application of this
      noble immunotherapy enabling to selectively target cytokines, e.g. TNFalpha, in
      RA as well as in other inflammatory autoimmune diseases in the near future.

PMID- 17549870
TI  - Role of fine needle aspiration cytology (FNAC) in the diagnosis of prostatic
      lesions with histologic correlation.
AB  - This study was carried-out to evaluate the diagnostic accuracy of fine needle
      aspiration cytology (FNAC) and the role of FNAC in the diagnosis of prostatic
      lesions. FNAC was performed on 64 patients presented with enlarged prostate.
      Cytological diagnosis by fine needle aspiration (FNA) of the prostate was
      compared with histological diagnosis in 60 patients. Of these, 42 cases were
      cytologically diagnosed as benign lesions, 18 cases as malignant. In remaining 4
      cases, materials were inadequate for diagnosis in one case and biopsy materials
      were not available in 3 cases. On histological examination, 42 cases which were
      cytologically diagnosed as benign, 40 cases were found to be benign and 2 cases
      were malignant histologically leading to 2 false negative diagnoses. Of the 18
      cases diagnosed cytologically as malignant (considering atypical hyperplasia and
      carcinoma as malignant), 15 cases were proved to be so by histological
      examination. So there were false positive diagnoses in 3 cases. No patient
      suffered from any complication following the aspiration biopsy. The sensitivity
      of this study for detection of prostatic carcinoma was 88 percent; specificity
      was 93 percent and diagnostic accuracy 91.7 percent. In this prospective study,
      FNAC of prostate was found to be associated with high diagnostic yields. These
      data support the value of transrectal FNAC as sensitive, easy to perform method
      for sampling of an enlarged prostate. The procedure may be used as an efficient
      primary screening tool in the diagnosis of prostatic lesions. Frequent use of
      this technique in our country should be encouraged.

PMID- 17549871
TI  - Treatment of lower ureteric stones by ESWL and ICPL: a comparative study.
AB  - This study was carried-out to find-out better and effective treatment option for
      Lower Ureteric Stones (LUS) by comparing Extracorporeal Shock Wave Lithotripsy
      (ESWL) with ureterorenoscopic (URS) Intracorporeal Pneumatic Lithotripsy (ICPL).
      A total of 60 patients attending the outpatient department of Bangabandhu Sheikh
      Mujib Medical University (BSMMU) with lower ureteric stones were divided into two
      groups, 30 in group-I (URS + ICPL) and the remaining 30 in group-II (ESWL). In
      group-I, 60% were male with mean age of 32.76 years and in group-II, 40% were
      male with mean age of 36.23 years. The ratio of involvement of right to left
      ureter was 1.7:1. The mean stone size was 10.7 + 2.69 mm (SD) in group-I and 9.9
      + 1.97 mm (SD) in group-II. The differences in age, sex and side of involvement
      of ureter were not significant (p > 0.05) between the two groups. Among the
      groups 24 (80%) in group-I and 26 (86.61%) of patients in group-II were found
      stone free. The post procedure loin pain, fever and haematuria were more common
      in group-I than in group-II. The LUTS and loin pain were significantly more in
      group-I than in group-II (p < 0.05). The post procedure fever was significantly
      more in group-I than in group-II (p < 0.001). The mean post procedure hospital
      stay was 5.7 + 2.54 days for group-I and 1.57 + 0.531 days for group-II. Post
      procedure hospital stay was significantly less in group-II than in group-I (p <
      0.05). The post procedure follow up attendance in this study was significantly
      low in group-I than in group-II (p < 0.05). ESWL was found effective method than
      URS + ICPL for the treatment of lower ureteric stones.

PMID- 17549872
TI  - Trend of selected risk factors for hepatitis B infection among the drug addicts
      in Bangladesh: a five year statistics.
AB  - The present retrospective study was conducted by review of records of last five
      years from 1996 to 2000, among 1497 drug addicts, admitted in a selected drug
      addicts treatment centre in Dhaka, with an aim to find out the trend of
      occurrence of hepatitis B infection among the drug addicts, as well as the trend
      of the risk factors. It was found from the study that during the period of five
      years, among the total drug addicts, sixty-nine addicts were found to be
      hepatitis B positive as determined by HBsAg status. The main contributing risk
      factors were found to be history of exposure to the commercial sex workers (CWS),
      injecting drug use (IDUs) and needle sharing. It was also found that the trend of
      hepatitis B infection was gradually falling down among the drug addicts probably
      due to reduction of the risk factors, especially the injection of drugs. It can
      be recommended that as a considerable portion of (NUDS) have shown evidence of
      hepatitis B infection, especially those who were using and sharing needles with
      others. Therefore, for protecting them from this dreadful infection, drug addicts
      should be counseled to avoid the above high risk behavior.

PMID- 17549873
TI  - Aneurysmal bone cyst of sphenoid bone--a case report.
AB  - Aneurysmal bone cysts of the skull are rare and involvement of sphenoid bone is
      even less frequent. We present X-ray, CT, MR imaging and histopathologic findings
      of an aneurismal bone cyst of the sphenoid in a 15-years old female adolescent.
      Radiological findings of the aneurysmal bone cyst of the skull were highly
      suggestive of the diagnosis and that were confirmed by histopathologic analysis.

PMID- 17549874
TI  - Single-band amplitude demodulation of Muller-Lyer illusion images.
AB  - The perception of the Muller-Lyer illusion has previously been explained as a
      result of visual low band-pass spatial filtering, although, in fact, the illusion
      persists in band-pass and high-pass filtered images without visible low-spatial
      frequencies. A new theoretical framework suggests that our perceptual experience
      about the global spatial structure of an image corresponds to the amplitude
      modulation (AM) component (or its magnitude, also called envelope) of its AM-FM
      (alternatively, AM-PM) decomposition. Because demodulation is an ill-posed
      problem with a non-unique solution, two different AM-FM demodulation algorithms
      were applied here to estimate the envelope of images of Muller-Lyer illusion: the
      global and exact Daugman and Downing (1995) AMPM algorithm and the local and
      quasi-invertible Maragos and Bovik (1995) DESA. The images used in our analysis
      include the classic configuration of illusion in a variety of spatial and spatial
      frequency content conditions. In all cases, including those of images for which
      visual low-pass spatial filtering would be ineffective, the envelope estimated by
      single-band amplitude demodulation has physical distortions in the direction of
      perceived illusion. It is not plausible that either algorithm could be
      implemented by the human visual system. It is shown that the proposed second
      order visual model of pre-attentive segregation of textures (or "back-pocket"
      model) could recover the image envelope and, thus, explain the perception of this
      illusion even in Muller-Lyer images lacking low spatial frequencies.

PMID- 17549875
TI  - Inner and outer horizons of time experience.
AB  - Human experience of temporal durations exhibits a multi-regional structure, with
      more or less distinct boundaries, or horizons, on the scale of physical duration.
      The inner horizons are imposed by perceptual thresholds for simultaneity
      (approximately equal to 3 ms) and temporal order (approximatly equal to 30 ms),
      and are determined by the dynamical properties of the neural substrate
      integrating sensory information. Related to the inner horizon of experienced time
      are perceptual or cognitive "moments." Comparative data on autokinetic times
      suggest that these moments may be relatively invariant (approximately equal to
      10(2) ms) across a wide range of species. Extension of the "sensible present"
      (approximately equal to 3 s) defines an intermediate horizon, beyond which the
      generic experience of duration develops. The domain of immediate duration
      experience is delimited by the ultimate outer horizon at about = 10(2) s, as
      evidenced by analysis of duration reproduction experiments (reproducibility
      horizon), probably determined by relaxation times of "neural accumulators."
      Beyond these phenomenal horizons, time is merely cognitively (re)constructed, not
      actually experienced or "perceived," a fact that is frequently ignored by
      contemporary time perception research. The nyocentric organization of time
      experience shows an interesting analogy with the egocentric organization of
      space, suggesting that structures of subjective space and time are derived from
      active motion as a common experiential basis.

PMID- 17549876
TI  - Computerized stroop test to assess selective attention in children with attention
      deficit hyperactivity disorder.
AB  - Research shows abnormal function of the pre-frontal cortex in Attention Deficit
      Hyperactivity Disorder (ADHD). This cortex is involved in the control of
      executive functions related to planning and execution of goal-oriented
      strategies, working memory, inhibitions, cognitive flexibility, and selective
      attention. Selective attention involves focus on the target stimulus, ignoring
      competing distractions. The Stroop Test (Stroop, 1935) is usually used to
      evaluate selective attention. This study investigated whether children with ADHD
      could exhibit modified performance in the Stroop Test. Using a computerized
      version of this test (Capovilla, Montiel, Macedo, & Charin, 2005), the study
      compared the reaction times (RTs) of 62 Brazilian children, between 8 and 12
      years of age, 31 of whom were diagnosed with ADHD and sent to psychiatric
      clinics, and 31 without ADHD studying in regular schools. All children with ADHD
      satisfied the criteria of the DSM-IV-TR and were evaluated with the Conners
      Abbreviated Questionnaire (Goyette, Conners, & Ulrich, 1978), completed by
      parents and teachers. The results revealed that children with ADHD exhibit
      greater interference in RT than children without ADHD. This corroborated the
      hypothesis that children with ADHD exhibit a deficit in selective attention,
      consisting in augmented RTs, as measured by the Computerized Stroop Test.

PMID- 17549877
TI  - A neurocognitive approach to the study of private speech.
AB  - The paper presents the current state of the art of research identifying the
      neurophysiological and neuroanatomical substrates of private speech, both in
      typical and clinical (or atypical) populations. First, it briefly describes the
      evolution of private speech research, which goes from classic traditions as the
      naturalistic and referential paradigms to the neurocognitive approach. An
      overview of the neurophysiological (e.g., event-related potentials or ERPs) and
      neuroimaging techniques (e.g., functional magnetic resonance imaging or fMRI) is
      also presented. The next three sections review empirical works about the
      neurocognitive basis of private speech, across three groups of techniques: ERPs;
      fMRI/MRI; and other neuroimaging techniques (positron emission tomography [PET],
      magnetoencephalogram [MEG], and repetitive transcranial magnetic stimulation
      [rTMS]). Such neurocognitive research analyzes the neural activity of individuals
      during a variety of task settings, including spontaneous and instructed overt and
      inner private speech use, subvocal verbalizations, and silent and overt reading.
      The fifth section focuses on electrophysiological and neuroimaging studies of
      private speech in atypical populations, for example: schizophrenia, pure alexia,
      hearing impairment, blindness, social phobia, alexithymia, Parkinson, and
      multiple sclerosis. The neurocognitive study of the various forms of private
      speech appears to be very promising in the understanding of these pathologies.
      Lastly, the advances and new challenges in the field are discussed.

PMID- 17549878
TI  - Computer speech-based remediation for reading disabilities: the size of spelling
      to-sound unit in a transparent orthography.
AB  - This study was designed to assess the effects of four reading-training procedures
      for children with reading disabilities (RD) in a transparent orthography, with
      the aim of examining the effects of different spelling-to-sound units in computer
      speech-based reading. We selected a sample of 83 Spanish children aged between 7
      years 1 month and 10 years 6 months (M = 105.2, SD = 7.8) whose pseudoword
      reading performance was below the 25th percentile and IQ > 90. The participants
      were randomly assigned to five groups: (a) the whole-word training group (WW) (n
      = 17), (b) the syllable training group (S)(n = 16), (c) the onset-rime training
      group (OR) (n = 17), (d) the phoneme training group (P) (n = 15), and (e) the
      untrained control group (n = 18). Children were pre- and post-tested in word
      recognition, reading comprehension, phonological awareness, and orthographic and
      phonological tasks. The results indicate that experimental groups who
      participated in the phoneme and syllable conditions improved their word
      recognition in comparison with the control group. In addition, dyslexics who
      participated in the phoneme, syllable, and onset-rime conditions made a greater
      number of requests during computer-based word reading under conditions that
      required extensive phonological computation (low frequency words and long words).
      Reading time, however, was greater for long words in the phoneme group during
      computer-based reading. These results suggest the importance of training
      phonological processes in improving word decoding in children with dyslexia who
      learn in a consistent orthography.

PMID- 17549879
TI  - Constructing personality maps, mapping personality constructs: multidimensional
      scaling recovers the big five factors from internal and external structure.
AB  - This report examines the structure of similarities underlying the lexicon of
      personality-trait description, when "similarity" is defined and measured in terms
      of (a) semantic judgment and (b) covariance in actual use. A lexicon of 60 trait
      adjectives was examined, using several procedures for collecting semantic
      judgments. Similarity data of both kinds were analyzed with multidimensional
      scaling (MDS) to provide a parsimonious representation of underlying structure.
      The convergence between semantic judgments and covariance within trait
      attribution data was substantial; both kinds of data evinced the same structure
      when collected for subsets of adjectives. Canonical correlation was employed to
      find the number of dimensions shared across MDS solutions. Interpretation of the
      results was facilitated by individual-differences MDS, which can select an
      optimal set of underlying dimensions, and at the same time accommodate the
      differences between data sets that arise when data-collection procedures differ
      in the relative emphasis they place upon those dimensions. We interpret the small
      number and shared nature of the dimensions by arguing that the lexicon's
      structure relates to trait perception rather than personality structure per se,
      even when probed with trait-attribution covariance.

PMID- 17549880
TI  - Fatherhood as a personality development factor in men.
AB  - The article represents an empirical study of paternity as a male personality
      development factor in men. Consensus is emerging that responsible fatherhood
      entitles the father to establish paternity, be present in the child's life, share
      economic support, and be personally involved in the child's life in collaboration
      with the mother. Literature reviews on fatherhood yield numerous empirical
      studies of specific fatherhood behaviors, whereas theory and the "bigger picture"
      have been notably insufficient. In the present article, problems of fatherhood in
      modern society, methodological problems of studying fathering, and cultural
      specifics of fatherhood are discussed. In addition, in order to aid further study
      of the phenomenon, the theoretically developed and experimentally approved model
      of the structure of paternity and the description of a specially developed
      training for fathers are presented. A principal finding of this report is that
      fatherhood is socially determined and influenced by contextual forces within the
      family and the community. The absence of a father-figure is detrimental to child
      personality development. At the same time, fatherhood can be a factor of male
      personality development of the father.

PMID- 17549881
TI  - Perceptions of self-concept and self-presentation by procrastinators: further
      evidence.
AB  - Two samples of university students completed self-report measures of chronic
      procrastination and either self-concept variables (Sample 1, n = 233) or self
      presentational styles (Sample 2, n = 210). Results indicated that procrastination
      was significantly related to a self-concept of oneself as dominated by issues
      related to task performance, and to self-presentation strategies that reflected a
      person as continually justifying and excusing task delays and being "needy" of
      others' approval. It seems that men and women procrastinate in order to improve
      their social standing by making their accomplishments seem greater than they
      really are.

PMID- 17549882
TI  - Underlying dimensions of ecocentric and anthropocentric environmental beliefs.
AB  - This study focuses on the cognitive components of general environmental
      attitudes. Taking as a starting point the scale of Thompson and Barton (1994) to
      identify ecocentric and anthropocentric motives in environmental conservation,
      the beliefs that guide attitudes in the person-environment relationship are
      analyzed. Confirmatory factor analysis was used to contrast the tripartite
      structure of these beliefs--based on egoistic, socioaltruistic, and biospheric
      aspects-with a two-dimensional structure that confronts ecocentric and
      anthropocentric orientations. The results obtained from two samples, a student
      sample (n = 212) and a sample from the general population of Madrid (n = 205),
      indicate the existence of a three-dimensional structure of environmental beliefs:
      an anthropocentric dimension based on the instrumental value of the environment
      for human beings, a biospheric dimension that values the environment for its own
      sake, and, lastly, an egobiocentric dimension that values the human being within
      nature as a whole.

PMID- 17549883
TI  - A survey of women's social representations of aging and rejuvenation.
AB  - The goal of this work was to analyze the social representations that women of
      three different age groups had about aging, rejuvenating, and methods of
      rejuvenation. The research was performed in Sao Paulo between 2004 and 2005. The
      participants of this research were three groups of women of different ages: 19 to
      24 years, 25 to 35 years, and over 60 years. The data were collected by the focus
      group technique. Data was analyzed using the lexical analysis software ALCESTE
      4.5. The main results show a social representation of aging centered on losses
      and gains. The subjects appraised the possibility of using rejuvenating methods
      only when it was extremely necessary, because of the health risks that most of
      them involve. The three groups agreed about natural methods of rejuvenating
      instead of resorting to invasive methods.

PMID- 17549884
TI  - Prediction of longevity of volunteer service: a basic alternative proposal.
AB  - A problem for many organizations is the low continuity of volunteers. Diverse
      theoretical models have been developed to explain sustained volunteerism, but
      most of these models have focused on the study of welfare volunteerism and not
      have verified whether their results could be generalized to other types of
      volunteerism. In this study, we propose a basic model to explain sustained
      volunteerism in any type of volunteerism. The aim of this study is to examine
      this basic model empirically in a sample of socio-assistential volunteers and in
      a sample of environmental volunteers. For this purpose, 290 volunteers completed
      a questionnaire and subsequently, two telephone follow-ups were carried out to
      determine whether the volunteers remained in the NGO one year later. The results
      show that the basic model offers an acceptable explanation of sustained
      volunteerism in the two types of volunteer samples studied, but it accounted for
      a low percentage of variance of the duration of service in both samples. Various
      relevant implications for the practical management of volunteerism in
      organizations are derived from theses findings.

PMID- 17549885
TI  - Social comparison and perceived breach of psychological contract: their effects
      on burnout in a multigroup analysis.
AB  - This study focuses on the mediator role of social comparison in the relationship
      between perceived breach of psychological contract and burnout. A previous model
      showing the hypothesized effects of perceived breach on burnout, both direct and
      mediated, is proposed. The final model reached an optimal fit to the data and was
      confirmed through multigroup analysis using a sample of Spanish teachers (N =
      401) belonging to preprimary, primary, and secondary schools. Multigroup analyses
      showed that the model fit all groups adequately.

PMID- 17549886
TI  - Justification of violence beliefs and social problem-solving as mediators between
      maltreatment and behavior problems in adolescents.
AB  - This study examined whether justification of violence beliefs and social problem
      solving mediated between maltreatment experiences and aggressive and delinquent
      behavior in adolescents. Data were collected on 191 maltreated and 546
      nonmaltreated adolescents (ages 14 to 17 years), who completed measures of
      justification of violence beliefs, social problem-solving dimensions (problem
      orientation, and impulsivity/carelessness style), and psychological problems.
      Findings indicated that maltreated adolescents' higher levels of delinquent and
      aggressive behavior were partially accounted for by justification of violence
      beliefs, and that their higher levels of depressive symptoms were partially
      mediated by a more negative orientation to social problem-solving. Comparisons
      between boys and girls indicated that the model linking maltreatment, cognitive
      variables, and psychological problems was invariant.

PMID- 17549887
TI  - Self-concept, self-esteem and psychopathological symptoms in persons with
      intellectual disability.
AB  - The purpose of this study is two-fold: (a) to analyze self-concept, self-esteem,
      and psychopathological symptoms in individuals with and without intellectual
      disability; and (b) to explore whether there were gender differences in these
      same variables in both groups. The sample is made up of 170 participants aged 19
      to 40, 128 without disability and 42 with intellectual disability. The
      methodology is descriptive. To measure the variables, three assessment
      instruments were applied: the "Listado de adjetivos para la evaluaci6n del
      autoconcepto en adolescentes y adultos" (LAEA; Garaigordobil, in press), the
      Rosenberg Self-Esteem Scale (RSE; Rosenberg, 1965), and the Revised Symptom
      Checklist-90 (SCL-90; Derogatis, 1983). The ANOVA showed that participants with
      intellectual disability scored significantly lower in self-concept and self
      esteem, and higher in all the psychopathological symptoms except for
      somatization. The ANOVA did not reveal significant gender differences in any
      variables in either of the two groups.

PMID- 17549888
TI  - Emotional ambivalence in risk behaviors: the case of occasional excessive use of
      alcohol.
AB  - The purpose of this paper is to study the differential and complementary role
      played by the theory of planned behavior (TPB) variables and by participants'
      emotions when recalling and describing previous experiences of such risk behavior
      in the prediction of the intention to repeat a risk behavior in the immediate
      future. We chose the behavior of occasional excessive drinking, a risk behavior
      characterized by evoking attitudinal ambivalence and eliciting mixed emotions,
      joy and sadness. The results show that emotional ambivalence is not equivalent to
      attitudinal ambivalence (whose indexes include that of the affective component),
      and that this emotional information is relevant for predicting the intention to
      repeat the risk behavior in the near future, enhancing the prediction of the TPB
      model.

PMID- 17549889
TI  - Anxiety sensitivity and panic symptomatology: the mediator role of
      hypochondriacal concerns.
AB  - The present study tests the mediating role of hypochondriasis to explain the
      relation between anxiety sensitivity and panic symptomatology. Fifty-seven
      outpatients with clinically significant levels of panic symptomatology were
      selected to participate in the study. Measures of anxiety sensitivity,
      hypochondriasis, and panic symptomatology were obtained from standardized, self
      administered questionnaires: the Anxiety Sensitivity Index (ASI; Reiss, Peterson,
      Gursky, & McNally, 1986), the Whiteley Index of Hypochondriasis (WI; Pilowsky,
      1967), and the Panic-Agoraphobic Spectrum Self-Report (PAS-SR; Cassano et al.,
      1997; Shear et al., 2001). Regression analyses were performed to test for the
      mediation models. The results show that the effect of anxiety sensitivity on
      panic symptomatology is not significant when controlling the hypochondriacal
      concerns, whereas the latter predicted panic symptoms. This result holds for the
      overall ASI as well as for the Physical Concerns and the Mental Incapacitation
      Concerns dimensions of the ASI scale. No evidence of a direct relation between
      the Social Concerns dimension and panic symptoms was found. The findings suggest
      that hypochondriacal concerns might represent the mechanism through which anxiety
      sensitivity is able to influence panic symptoms.

PMID- 17549890
TI  - Electroencephalographic intercentral interaction as a reflection of normal and
      pathological human brain activity.
AB  - The authors summarized EEG findings and defined the nature of the intercentral
      EEG relationships in different functional states in healthy subjects and patients
      with organic cerebral pathology, based on a coherence analysis. Similar EEG
      characteristics in healthy individuals were identified: an anterior-posterior
      gradient of average coherence levels, the type of cortical-subcortical
      relationships in anterior cerebral structures. Right- and left-handed individuals
      showed frequent and regional differences in EEG coherence, which mainly reflected
      specificity of intracortical relationships. Development and regression of
      pathology in right-and left-handed individuals with organic brain lesions were
      thought to be caused by these differences. Lesions of regulatory structures
      (diencephalic, brain stem and limbic structures) provoked a more diffused kind of
      changes of intercentral relationships, in contrast to cortical pathology. These
      changes tended to reciprocate. The dynamic nature of intercentral relationships
      and their interhemispheric differences was revealed when changing functional
      states of the brain (increase and decrease of functional level) in healthy
      individuals and patients with organic cerebral pathology in the process of
      conscious and psychic activity restoration. Changing activity predominance of
      certain regulatory structures was considered one of the most important factors
      determining the dynamic nature of EEG coherence.

PMID- 17549892
TI  - The theory of thinking and the capacity to mentalize: a comparison of Fonagy's
      and Bion's models.
AB  - This paper presents a comparison of two psychoanalytic models of how human beings
      learn to use their mental capacities to know meaningfully about the world. The
      first, Fonagy's model of mentalization, is concerned with the development of a
      self capable of reflecting upon its own and others' mental states, based on
      feelings, thoughts, intentions, and desires. The other, Bion's model of thinking,
      is about the way thoughts are dealt with by babies, facilitating the construction
      of a thinking apparatus within a framework of primitive ways of communication
      between mother and baby. The theories are compared along three axes: (a) an axis
      of the theoretical and philosophical backgrounds of the models; (b) an axis of
      the kind of evidence that supports them; and (c) the third axis of the technical
      implications of the ideas of each model. It is concluded that, although the
      models belong to different theoretical and epistemological traditions and are
      supported by different sorts of evidence, they may be located along the same
      developmental line using an intersubjective framework that maintains tension
      between the intersubjective and the intrapsychic domains of the mind.

PMID- 17549891
TI  - Psychophysiological analysis of the influence of vasopressin on speech in
      patients with post-stroke aphasias.
AB  - Speech is an attribute of the human species. Central speech disorders following
      stroke are unique models for the investigation of the organization of speech.
      Achievements in neurobiology suggest that there are possible neuroendocrine
      mechanisms involved in the organization of speech. It is known that the
      neuropeptide vasotocin, analogous of vasopressin in mammals, modulates various
      components of vocalization in animals. Furthermore, the positive influence of
      vasopressin on memory, which plays an important role in the formation of speech,
      has been described. In this study, speech organization processes and their
      recovery with the administration of vasopressin (1-desamino-8-D-arginin
      vasopressin) to 26 patients with chronic aphasias after stroke were investigated.
      Results showed that sub-endocrine doses of the neuropeptide with intranasal
      administration had positive influence primarily on simple forms of speech and
      secondarily on composite forms. There were no statistically significant
      differences between the sensory and integrative components of the organization of
      speech processes with vasopressin. In all cases, the positive effect of the
      neuropeptide was demonstrated. As a result of the effects, speech regulated by
      both brain hemispheres improved. It is suggested that the neuropeptide optimizes
      the activity both in the left and right hemispheres, with primary influence on
      the right hemisphere. The persistence of the acquired effects is explained by an
      induction of compensatory processes resulting in the reorganization of the intra
      central connections by vasopressin.

PMID- 17549894
TI  - 'NHS family' accused of stifling entrepreneurialism.

PMID- 17549893
TI  - Factor structure of the Perceived Stress Scale (PSS) in a sample from Mexico.
AB  - The aim of this study was to analyze the cultural adaptation of the European
      Spanish version of the Perceived Stress Scale (PSS; Cohen, Kamarak, &
      Mermelstein, 1983), for its use in Mexican samples. Using a random sample of
      students, internal consistency was analyzed and the factor structure of the
      Spanish version of the PSS was compared with the factor structure found in the
      English version. Internal consistency was adequate (alpha = .83) and confirmatory
      factor analysis corroborated the factor structure. Factor 1 explained 42.8% of
      the variance and Factor 2 accounted for 53.2%. The goodness-of-fit measures also
      revealed an adequate fit. The cultural adaptation of the PSS was also evaluated
      with satisfactory results.

PMID- 17549895
TI  - New management teams tackle commissioning.

PMID- 17549896
TI  - Finance. Have trusts turned the corner, or just papered over the cracks?

PMID- 17549897
TI  - On going back to the floor.

PMID- 17549898
TI  - Care UK chief urges swift ISTC take-up. Interview by Helen Mooney.

PMID- 17549899
TI  - Barometer. Acute trusts May 2007.

PMID- 17549900
TI  - Mental health. Behind locked doors.
AB  - The maximum-security Broadmoor Hospital is home to around 300 'damaged people'.
      The hospital has been unequivocally declared unfit for purpose, but plans to
      demolish it could take until 2014. The average length of stay is five to seven
      years--so care should be focused in rehabilitation.

PMID- 17549901
TI  - Healthy staff will enhance outcomes.

PMID- 17549902
TI  - Maternity services. The mother of all tasks.

PMID- 17549903
TI  - Strategic planning, the hospital board, and you. Board members can prove a
      valuable asset in strategic marketing.

PMID- 17549904
TI  - Weigh risks, rewards of joint hospital-physician advertising.

PMID- 17549905
TI  - It takes more than a people person to manage a sales team.

PMID- 17549906
TI  - Transition detection in body movement activities for wearable ECG.
AB  - It has been shown by Pawar et al. (2007) that the motion artifacts induced by
      body movement activity (BMA) in a single-lead wearable electrocardiogram (ECG)
      signal recorder, while monitoring an ambulatory patient, can be detected and
      removed by using a principal component analysis (PCA)-based classification
      technique. However, this requires the ECG signal to be temporally segmented so
      that each segment comprises of artifacts due to a single type of body movement
      activity. In this paper, we propose a simple, recursively updated PCA-based
      technique to detect transitions wherever the type of body movement is changed.

PMID- 17549907
TI  - Drug uptake enhancement using sonodynamic effects at 4 MHz--a potential
      application for micro-ultrasonic-Transducers.
AB  - Sonodynamic therapy is a cancer treatment method that uses macro scale ultrasound
      devices to enhance the cytotoxic efficacy of anticancer drugs, such as
      doxorubicin [1]. In this paper, unconventional, miniature ultrasound transducers
      (5 mm x 5 mm x 0.5 mm) were used to create a tone-burst ultrasound (4 MHz, 32
      Watt/cm(2), 20% duty cycle, 50 ms burst period). It was found that the transducer
      significantly (p < 0.01) enhanced the immediate cells lysis when combining with
      doxorubicin (20 microM) in human prostate cancer cells (PC3). With a 30-s
      ultrasound exposure, the immediate cell lysis and long-term cytotoxicity were
      enhanced by 70% and 83%, respectively, compared to controls. We have demonstrated
      that ultrasound in combination with doxorubicin could strongly inhibit tumour
      cell proliferation in vitro at lower doses of the drug. This work is a first step
      towards a microelectromechanical system (MEMS)-based, implantable micro
      ultrasonic transducers (MUTs) that could be used in sonodynamic therapy.

PMID- 17549908
TI  - Shape memory polymer stent with expandable foam: a new concept for endovascular
      embolization of fusiform aneurysms.
AB  - We demonstrate a new concept for endovascular embolization of nonnecked fusiform
      aneurysms. A device prototype consisting of a stent augmented with expandable
      foam, both made from shape memory polymer, was fabricated and deployed in an in
      vitro model. Visual observation indicated that the foam achieved embolization of
      the aneurysm while the stent maintained an open lumen in the parent artery. The
      shape memory polymer stent-foam device is a potential tool for treatment of
      nonnecked fusiform aneurysms, as well as an alternative to stent- and balloon
      assisted coil embolization of wide-necked aneurysms.

PMID- 17549909
TI  - The tendon network of the fingers performs anatomical computation at a
      macroscopic scale.
AB  - Current thinking attributes information processing for neuromuscular control
      exclusively to the nervous system. Our cadaveric experiments and computer
      simulations show, however, that the tendon network of the fingers performs logic
      computation to preferentially change torque production capabilities. How this
      tendon network propagates tension to enable manipulation has been debated since
      the time of Vesalius and DaVinci and remains an unanswered question. We
      systematically changed the proportion of tension to the tendons of the extensor
      digitorum versus the two dorsal interosseous muscles of two cadaver fingers and
      measured the tension delivered to the proximal and distal interphalangeal joints.
      We find that the distribution of input tensions in the tendon network itself
      regulates how tensions propagate to the finger joints, acting like the switching
      function of a logic gate that nonlinearly enables different torque production
      capabilities. Computer modeling reveals that the deformable structure of the
      tendon networks is responsible for this phenomenon; and that this switching
      behavior is an effective evolutionary solution permitting a rich repertoire of
      finger joint actuation not possible with simpler tendon paths. We conclude that
      the structural complexity of this tendon network, traditionally oversimplified or
      ignored, may in fact be critical to understanding brain-body coevolution and
      neuromuscular control. Moreover, this form of information processing at the
      macroscopic scale is a new instance of the emerging principle of nonneural
      "somatic logic" found to perform logic computation such as in cellular networks.

PMID- 17549910
TI  - Simultaneous fetal magnetocardiography and ultrasound/Doppler imaging.
AB  - The difficulty of utilizing multimodality diagnostic imaging techniques for fetal
      surveillance remains one of the greatest challenges in providing enhanced
      prenatal care. In this Letter we demonstrate the feasibility of performing fetal
      magnetocardiography (fMCG) and ultrasound/Doppler imaging simultaneously, using a
      multichannel SQUID magnetometer and a portable ultrasound scanner. Despite large
      magnetic interference from the scanner, the implementation of simple noise
      reduction procedures and appropriate signal processing techniques yielded fMCG
      recordings of sufficient quality for assessment of fetal heart rate and rhythm. A
      variation of reference channel filtering, referred to here as synthetic reference
      channel filtering, was used to reduce nonstationary low-frequency interference.
      The combination of fMCG and/or fMEG with ultrasound/Doppler offers new
      possibilities for assessment of fetal well-being and fetal cardiac function.

PMID- 17549911
TI  - Frequency recognition based on canonical correlation analysis for SSVEP-based
      BCIs.
AB  - Canonical correlation analysis (CCA) is applied to analyze the frequency
      components of steady-state visual evoked potentials (SSVEP) in
      electroencephalogram (EEG). The essence of this method is to extract a narrowband
      frequency component of SSVEP in EEG. A recognition approach is proposed based on
      the extracted frequency features for an SSVEP-based brain computer interface
      (BCI). Recognition Results of the approach were higher than those using a widely
      used FFT (fast Fourier transform)-based spectrum estimation method.

PMID- 17549912
TI  - Encouraging hands-on experience in BME education.

PMID- 17549913
TI  - Landing a job in industry.

PMID- 17549914
TI  - Health technology in Europe.

PMID- 17549915
TI  - Medical and biological engineering and science in the European higher education
      area.

PMID- 17549916
TI  - Biomedical engineering and eHealth in Europe.

PMID- 17549917
TI  - Advanced wearable health systems and applications.

PMID- 17549918
TI  - Biomedical informatics and healthGRIDs: a European perspective.

PMID- 17549919
TI  - A roadmap for NeuroIT.

PMID- 17549920
TI  - New technologies supporting surgical interventions and training of surgical
      skills.

PMID- 17549921
TI  - Engineering for health.

PMID- 17549922
TI  - Improving corrective maintenance efficiency in clinical engineering departments.

PMID- 17549923
TI  - Effects of simulated hypergravity on biomedical experiments.

PMID- 17549924
TI  - Medline: the knowledge buried therein, its potential, and cost.

PMID- 17549925
TI  - Biomedical engineering/industrial design collaboration in senior design projects.

PMID- 17549926
TI  - Who first performed cardiac pacing: why, when, and where?

PMID- 17549927
TI  - We, too, must evolve.

PMID- 17549928
TI  - Shape and function from motion in biomedical imaging: part 3.

PMID- 17549929
TI  - Ethical issues in defibrillator patients' quality of life.

PMID- 17549930
TI  - "No compensation" or "pro compensation": Moore v. Regents and default rules for
      human tissue donations.
AB  - The much studied case of Moore v. Regents of the University of California is
      often considered important in property law for denying property rights in human
      tissue. This widespread misunderstanding of Moore has not only misplaced the
      legal emphasis of human tissue donations on property law instead of contract law,
      but has also hindered the creation of a much-needed default rule governing the
      issue of compensation for donated tissue. While it is possible that the majority
      of donors rarely consider compensation as an incentive to donate, without a
      legally recognized default rule the law remains blurred as to what contractual
      provisions apply to the exchange between donor and researcher. This Article
      argues that the solution is a weak default rule of no compensation that may be
      overridden by evidence that the parties intended otherwise.

PMID- 17549931
TI  - Physician-assisted suicide: legal and ethical considerations.
AB  - As medicine's technical limits have become increasingly clear, Americans seem
      more willing to address end-of-life decisionmaking. A major development during
      the 1990s was physician assistance in dying: physician-assisted suicide in
      Michigan, Oregon's Death with Dignity Act, and developments in Europe, most
      notably The Netherlands. This evolution toward recognizing the appropriateness of
      assistance in dying raises legal and ethical issues for physicians and healthcare
      institutions such as nursing facilities and acute care hospitals. These issues
      include the effects on providers' values systems, the trust between patient and
      provider, and the "slippery slope" that voluntary, active assistance in dying
      will become involuntary, active assistance. This Article addresses the policy
      issues that institutions must confront in a changing environment.

PMID- 17549932
TI  - Notes and comments "High and dry?" The Public Readiness and Emergency
      Preparedness Act and liability protection for pharmaceutical manufacturers.
AB  - In an era filled with fears of bioterrorism, Congress approved the Public
      Readiness and Emergency Preparedness Act (PREPA) to encourage development of
      vaccines and other countermeasures. By providing pharmaceutical manufacturers
      with protection from liability for potential side effects, Congress has attempted
      to motivate manufacturers to produce a national stockpile of countermeasures. As
      part of PREPA, the government established a compensatory system intended to
      provide compensation to persons injured by countermeasures used during a public
      health emergency. Although the Act provides for a compensation fund, it fails to
      allocate monies for that fund. Thus, in the absence of further congressional
      action, PREPA will not provide compensation to those injured by countermeasures.
      Failing to assure the American public of a compensation program constitutes bad
      public policy and risks inspiring potential vaccinees to refuse necessary drugs.
      Additionally, arguments as to the constitutionality of the Act exist should
      Congress fail to adequately fund the program, and the existence of those
      arguments undermines the purpose of the Act--namely to assure pharmaceutical
      manufacturers that they will not be sued into oblivion should they attempt to aid
      national pandemic protection. In addition to detailing both the Act and the
      statutory precedent for congressional attempts to spur biodefense, this Article
      addresses important issues of healthcare, tort, and constitutional law that will
      continue to manifest themselves in this new era of bioterrorism.

PMID- 17549933
TI  - Doctors, apologies, and the law: an analysis and critique of apology laws.
AB  - This Article analyzes and critiques apology laws, their potential use, and
      effectiveness, both legally and ethically, in light of the strong professional
      norms that shape physicians' reaction to medical errors. Physicians are largely
      reluctant to disclose medical errors to patients, patients' families, and even
      other physicians. Some states have passed so-called apology laws in order to
      encourage physicians to disclose medical errors to patients. Apology laws allow
      defendants to exclude statements of sympathy made after accidents from evidence
      in a liability lawsuit. This Article examines potential barriers to physicians'
      disclosure of medical mistakes and demonstrates how the underlying problem may
      actually be rooted in professional norms-norms that will remain outside the scope
      of law's influence. The Article also considers other legal and policy changes
      that could help to encourage disclosure.

PMID- 17549934
TI  - Sample/recruitment process policy.

PMID- 17549935
TI  - The legacy of Adolf Meyer's comparative approach: Worcester rats and the strange
      birth of the animal model.
AB  - The breeding of albino rats had an enormous impact on experimental psychology in
      the twentieth century. Rats were, and for many questions still remain, the
      "standard animal" for laboratory research in neurology, psychology, and
      physiology. Albert Meyer was one of the figures most responsible for developing
      the albino rat as an experimental model. Despite Meyer's pioneering work with
      albino rats, his rat research has received only sparse attention. Little is known
      about the way in which the animal served Meyer's more famous psychiatric program.
      In this article, the author discusses the role that albino rats played in Meyer's
      animal research. He then turn to the contrast between the way in which Meyer
      viewed the animal's role in research and the way rats were later used as a
      laboratory "standard" to assure scientific generality. This comparison highlights
      the changes that occurred in comparative psychology in the twentieth century, and
      it further clarifies some of the concerns associated with the use of animal
      models today.

PMID- 17549936
TI  - Arnold Gesell and the maturation controversy.
AB  - This article examines the work of Arnold Lucius Gesell and argues that he not
      only paved the way for contemporary research in motor development, but that he
      and colleagues anticipated fundamental issues about growth that must be addressed
      by psychologists and neuroscientists who are committed to the advancement of
      developmental science. Arnold Lucius Gesell was a pioneer in developmental
      psychology when the field was in its infancy. He worked diligently for the rights
      of physically and mentally handicapped children to receive special education that
      would enable them to find gainful employment. Gesell's writings in books and
      popular magazines increased public awareness of and support for preschool
      education and better foster care for orphans. Despite these achievements, many of
      his successors have questioned his views about infant development. Developmental
      psychologists have criticized Gesell for proposing a stage theory of infant
      growth that has fallen into disfavor among contemporary researchers. His
      conception of development as a maturational process has been challenged for
      allegedly reducing complex behavioral, perceptual, and learning processes to
      genetic factors. The author rejects this overly simplistic interpretation and
      contends that Gesell's work continues to stand the test of time.

PMID- 17549937
TI  - Alexander F. Chamberlain: a life's work.
AB  - This article examines the life and work of Alexander Francis Chamberlain. Though
      he has received little attention since the early 1900s, the importance of this
      scholar should not be underestimated. Chamberlain made notable contributions to
      the body of knowledge in anthropology-a discipline that, at the time, was a
      combination of anthropological and psychological inquiry. His early work began
      with investigations into the cultures and languages of two Indian tribes
      indigenous to Canada and the northern United States and, within a few decades,
      positioned Chamberlain as the leading scholar in this domain. Beyond his
      ethnographic insights, Chamberlain queried the development of the child and wrote
      on the subject of childhood in world folklore. He concerned himself with a scope
      of worthwhile subjects ranging from linguistics to women's suffrage. No topic was
      out of range as all forms of human study addressed the need for seeing each group
      as a contributing force to humanity at large. Chamberlain emphasized that no
      single racial, ethnic, or religious group should be singled out as inherently
      superior to another, a belief far ahead of his time. This article is an attempt
      at drawing a picture of a man whose scholarly achievements and strength of
      character are captured in the depth and breadth of his writing.

PMID- 17549938
TI  - The fate of the forgotten: Chamberlain's work reconsidered.
AB  - This article discusses the early psychological traditions developed at Clark
      University under the guidance of G. Stanley Hall. Anthropology and cultural
      psychology are both rooted in the notion that humans are social beings. That idea
      constituted a brief moment of theoretical unity between psychology and
      anthropology in the study of human language in its psychological functions. In
      that context, the work of Alexander Chamberlain is explored as a major
      contribution. Chamberlain--if viewed in the jargon of our contemporary social
      scientists--was deeply "interdisciplinary" in his work. Despite the positive
      meaning of the term "interdisciplinary" in contemporary discourse about the
      social sciences, the realities of social organization of any science entail
      separation rather than integration. Chamberlain's work took place in parallel in
      anthropology and in developmental psychology under the interdisciplinary emphasis
      of "child study" as set up by G. Stanley Hall. Hall made child study the
      distinctive feature of the "Clark tradition" of psychology. Chamberlain's work
      constituted both the beginning and the end of the (miniscule) "Clark tradition"
      in anthropology.

PMID- 17549939
TI  - Culture-brain interactions.
AB  - One of the philosophical problems in neuroscience is seeing the trees before the
      forest. Indeed, it is essential to know how local events fit into the whole
      picture, but we must also look beyond correlations between stimuli and neural
      responses in one sensory nucleus. A lifelong dialogue between the environment and
      human brain begins at birth. Different environments enable different experiences;
      each experience is unique because culture gives it meaning. The eye tells the
      brain about each experience and the context in which it occurs. The brain
      records, transmits and recalls all events in their proper sequence and with
      attendant emotion. Culture gives behavior meaning. It helps us see beyond
      technique alone to better integrate diverse approaches to answering key questions
      about how the mind works.

PMID- 17549940
TI  - New design standards for theatre ventilation.
AB  - New legislation in The Netherlands concentrates on the importance of correct
      ventilation in operating theatres to prevent post-operative infections. H.J
      Nicolaas, of the Netherlands Board for Health Facilities, explains the new
      guidelines.

PMID- 17549941
TI  - Total building commissioning.
AB  - Healthcare facilities are generally commissioned according to standards laid down
      by specific stipulations or the consultant engineers. This commissioning process
      is normally only concerned with the physical functioning of the building services
      and is aimed at ensuring the installed services are operating according to the
      engineers' specifications. It is no longer acceptable just to conduct a thorough
      clean, commonly called a hospital clean, and consider that as adequate for
      patient occupation, writes Kevin Moon.

PMID- 17549942
TI  - Slip and trip prevention needs full attention.
AB  - Workplace slips and trips cost an estimated 500 pounds sterling million per year,
      and sometimes cause serious injuries. Health Estate Journal reproduces guidance
      issued by the Health and Safety Executive on how correct floor cleaning can
      prevent accidents.

PMID- 17549943
TI  - Overcoming telephone system difficulties.
AB  - Health Estate Journal reports on how a leading NHS Trust is resolving a telephone
      number shortage crisis and is ensuring it has capability to meet major incident
      call demands.

PMID- 17549944
TI  - Precast concrete 'has no equals'.
AB  - In one form or another, concrete has been around for some 7,000 years and will,
      it appears, continue being the sine qua non construction material for the
      foreseeable future, says John Milner, chairman of the Structural Precast
      Association. This article was first published in the March 2007 issue of Building
      Engineer.

PMID- 17549946
TI  - Ensuring electrical safety is maintained.
AB  - Bill Earlie of test instrument and precision measurement company Cropico explains
      the implications of new guidance on electrical installations in medical
      environments.

PMID- 17549945
TI  - Meeting water requirements system.
AB  - There is a plethora of legislation and guidelines relating to the control and
      supply of water in healthcare establishments. Here, Roy Minett, marketing manager
      of Rada in the UK, provides some advice on making sense of what is expected and
      required.

PMID- 17549947
TI  - Energy policies need holistic approach.
AB  - NHS Trusts are large energy consumers, and the health sector has been compelled
      to address conservation issues--for both environmental and financial reasons.
      Kevin Jones of Schneider Electric Services and Projects argues that hospitals'
      energy policies must consider holistic remedies.

PMID- 17549948
TI  - No-touch taps help combat C. diff spread.
AB  - Dart Valley's Mike Allen explains how no-touch taps can assist in the fight
      against an organism which continues to attract much attention.

PMID- 17549949
TI  - Stainless steel shine continues.
AB  - One of the most important materials in the modern healthcare environment,
      stainless steel is poised for an impressive future. Martin Tye, managing director
      of GEC Anderson--manufacturer of bespoke stainless steel solutions and a long
      standing supplier to the health sector--looks at the outlook for stainless steel
      and offers advice on its specification and use.

PMID- 17549950
TI  - The effect of trunk stability training on vertical takeoff velocity.
AB  - STUDY DESIGN: Randomized controlled trial with repeated measures. OBJECTIVES: To
      determine the effect of trunk stability training on vertical takeoff velocity.
      BACKGROUND: Trunk stability training is commonly used in sports training
      programs; however, the effects of stability training on performance enhancement
      are not known. Trunk stability training may provide a more stable pelvis and
      spine from which the leg muscles can generate action, may better link the upper
      body to the lower body, or may enhance leg muscle activation, thus promoting
      optimal force production during sporting activities such as a vertical jump.
      METHODS AND MEASURES: Fifty-five athletes were randomly assigned to 1 of 4
      training groups: trunk stability (TS), leg strength (LS), trunk stability and leg
      strength (TL), and control (CO). Subjects were tested 3 times: at pretraining,
      after 3 weeks of training, and after 9 weeks of training. A repeated-measures
      analysis of covariance (ANCOVA) was used to examine differences among groups for
      vertical takeoff velocity measured indirectly using a force plate. Pretraining
      takeoff velocity and body mass were used as covariates. RESULTS: After 3 and 9
      weeks, the training groups were not different from each other. After 9 weeks of
      training, all 3 training groups had a greater takeoff velocity than the control
      group (P<.05). After 3 weeks of training only the TS group had a greater takeoff
      velocity than the control group (P<.05). Only the TL group increased
      significantly in vertical takeoff velocity between the third- and ninth-week
      testing periods (P<.05). CONCLUSIONS: Nine weeks of trunk stability training was
      similarly effective in enhancing vertical takeoff velocity as leg strength
      training or the combination of trunk stability and leg strength training.

PMID- 17549951
TI  - Analysis of hip strength in females seeking physical therapy treatment for
      unilateral patellofemoral pain syndrome.
AB  - STUDY DESIGN: Cross-sectional. OBJECTIVES: To investigate whether females seeking
      physical therapy treatment for unilateral patellofemoral pain syndrome (PFPS)
      exhibit deficiencies in hip strength compared to a control group. BACKGROUND:
      Decreased hip strength may be associated with poor control of lower extremity
      motion during weight-bearing activities, leading to abnormal patellofemoral
      motions and pain. Previous studies exploring the presence of hip strength
      impairments in subjects with PFPS have reported conflicting results. METHODS AND
      MEASURES: Twenty females, aged 12 to 35 years, participated in the study. Ten
      subjects with unilateral PFPS were compared to 10 control subjects with no known
      knee pathologies. Hip abduction, extension, and external rotation strength were
      tested using a handheld dynamometer. A limb symmetry index (LSI) was used to
      quantify physical performance for all tests. RESULTS: The symptomatic limbs of
      subjects with PFPS exhibited impairments in hip strength for all variables
      tested. LSI values in subjects with PFPS (range, 71%-79%) were significantly
      lower than those in control subjects (range, 93%-101%) (P< or =.007). A secondary
      analysis of data normalized to body mass demonstrated that the symptomatic limbs
      of subjects with PFPS had 52% less hip extension strength (P<.001), 27% less hip
      abduction strength (P = .007), and 30% less hip external rotation strength (P=
      .004) when compared to the weaker limbs of control subjects. CONCLUSION: Females
      aged 12 to 35 presenting with unilateral PFPS demonstrate significant impairments
      in hip strength compared to control subjects when LSI values or body mass
      normalized values are used to quantify physical performance of the symptomatic
      limb.

PMID- 17549952
TI  - Influence of step height on quadriceps onset timing and activation during stair
      ascent in individuals with patellofemoral pain syndrome.
AB  - STUDY DESIGN: A case control study, with single observation. OBJECTIVES: To
      compare the onset timing and activation of the vastus medialis oblique (VMO) and
      vastus lateralis (VL) between subjects with and without patellofemoral pain
      syndrome (PFPS) at various step heights. BACKGROUND: It has been theorized that
      delayed or reduced VMO activity relative to the VL contributes to lateral
      patellar tracking and PFPS. However, conflicting evidence exists in the
      literature regarding this proposed mechanism. The lack of agreement among studies
      may be attributed to inconsistent knee flexion angles used in previous studies.
      METHODS AND MEASURES: Twenty subjects with PFPS (mean +/- SD age, 29.5 +/- 10
      years) and 20 control subjects (mean +/- SD age, 25.4 +/- 3.1 years) ascended 5
      different step heights, while knee kinematics and quadriceps EMG data were
      collected. Knee flexion angle at foot-step contact, VMO-VL onset timing, and
      VMO/VL activation ratios were analyzed between groups and step heights using 2
      factor analyses of variance (ANOVAs) with repeated measures (alpha = .05).
      RESULTS: Individuals with PFPS demonstrated 4.7 degrees (P = .038) more knee
      flexion at foot-step contact than control subjects. Despite greater knee flexion
      with increased step height (P<.001), no differences in onset timing or activation
      magnitude ratio were present between groups or across step heights. However,
      individuals with PFPS displayed a significantly increased activation duration
      ratio compared to the control group (P = .043). CONCLUSION: Quadriceps onset
      timing and activation magnitude during stair ascent was similar between
      individuals with and without PFPS, regardless of step height. Thus, the results
      of this study are in agreement with evidence indicating no difference in VMO-VL
      timing and VMO/VL activation magnitude ratio between individuals with and without
      PFPS.

PMID- 17549953
TI  - Differences in lower extremity kinematics between a bilateral drop-vertical jump
      and a single-leg step-down.
AB  - STUDY DESIGN: Mixed-model, repeated-measures design in a laboratory setting.
      OBJECTIVES: To examine the differences in hip, knee, and ankle kinematics between
      a bilateral drop-vertical jump and single-leg step-down. A secondary purpose was
      to examine gender differences in kinematics of the tasks. BACKGROUND: Both a drop
      vertical jump and step-down task have been used to evaluate lower extremity
      movement and injury risk. The differences in joint angles between these tasks
      have not been reported. METHODS AND MEASURES: Three-dimensional joint angles of
      the hip, knee, and ankle of 19 females and 18 males were evaluated with a high
      speed camera system while the subjects performed a bilateral drop-vertical jump
      and a single-leg step-down. Maximum joint angles were compared between tasks and
      genders using ANOVA models. eversion (12 degrees compared to 8 degrees) (P<.0005)
      and hip adduction (16 degrees compared to 1 degrees) (P= .03) than the drop
      vertical jump. Females had greater hip internal rotation in the step-down than in
      the drop-vertical jump (5 degrees compared to 2 degrees) (P = .02). When averaged
      across both tasks, females had greater knee abduction than males in both tasks (4
      degrees compared to 0 degrees) (P<.0005). CONCLUSIONS: The unilateral step-down
      task produced greater motion in the frontal and transverse planes at the ankle
      and hip, and would be appropriate in evaluating control of the hip. The bilateral
      drop-vertical jump produced greater knee abduction in both genders and may be
      appropriate for evaluating excessive knee abduction as a risk factor for
      noncontact anterior cruciate ligament injury, for example. The 2 tasks appear to
      challenge the neuromuscular system in different manners, and both should continue
      to be used in the investigation of injury risk.

PMID- 17549954
TI  - Posttraumatic ankle arthritis: an update on conservative and surgical management.
AB  - This manuscript offers current information regarding the examination,
      conservative treatment, and surgical treatment for individuals with posttraumatic
      arthritis. Although inflammatory and osteoarthritis can occur, posttraumatic
      arthritis is the most common form of arthritis to affect the ankle. Posttraumatic
      ankle arthritis occurs in a generally younger, active population. It is
      radiographically characterized by an asymmetrical degenerative process and may be
      associated with a history of trauma, instability, and/or lower extremity
      malalignment. When choosing between conservative/nonoperative versus surgical
      intervention, the extent of subchondral bone exposed and the time over which the
      arthritis has developed are factors that should be considered. The role and
      effectiveness for conservative treatment, such as medication, patient education,
      shoe modification, bracing, stretching, mobilization, strengthening, and symptom
      management, needs to be further determined. Surgical procedures for posttraumatic
      ankle arthritis can include distraction arthroplasty, arthrodesis, or total ankle
      arthroplasty. Unlike the relatively new procedure of distraction arthroplasty,
      the outcomes for arthrodesis have been well defined. Arthrodesis generally has a
      good outcome, but its limitations have been recognized. These limitations include
      the extended time required to achieve fusion, potential for nonunion, arthritis
      developing in adjacent joints, leg length discrepancy, malalignment, chronic
      edema, symptoms due to the hardware, stress fractures, and continued pain. While
      first generation total ankle arthroplasty led to poor results, advancements in
      prosthetic design and surgical technique have revived optimism regarding total
      ankle arthroplasty as an alternative to arthrodesis. The key for the future of
      total ankle arthroplasty may not be related to the development of newer ankle
      components but rather in refining the criteria to determine who would best
      benefit from joint replacement versus fusion.

PMID- 17549955
TI  - Lower extremity muscle activation and alignment during the soccer instep and side
      foot kicks.
AB  - STUDY DESIGN: Controlled laboratory study. OBJECTIVES: To quantify phase duration
      and lower extremity muscle activation and alignment during the most common types
      of soccer kick-the instep kick and side-foot kick. A second purpose was to test
      the hypotheses that different patterns of lower extremity muscle activation occur
      between the 2 types of kicks and between the kicking limb compared to the support
      limb. BACKGROUND: Soccer players are at risk for lower extremity injury,
      especially at the knee. Kicking the soccer ball is an essential, common, and
      distinctive part of a soccer player's activity that plays a role in soccer player
      injury. Regaining the ability to kick is also essential for soccer athletes to
      return to play after injury. METHODS: Thirteen male soccer players underwent
      video motion analysis and electromyography (EMG) of 7 muscles in both the kicking
      and supporting lower extremity (iliacus, gluteus maximus, gluteus medius, vastus
      lateralis, vastus medialis, hamstrings, gastrocnemius) and 2 additional muscles
      in the kicking limb only (hip adductors, tibialis anterior). Five instep and 5
      side-foot kicks were recorded for each player. Analysis-of-variance models were
      used to compare EMG activity between type of kicks and between the kicking and
      nonkicking lower extremity. RESULTS: Five phases of kicking were identified: (1)
      preparation, (2) backswing, (3) limb cocking, (4) acceleration, and (5) follow
      through. Comparing the kicking limb between the 2 types of kick, significant
      interaction effects were identified for the hamstrings (P = .02) and the tibialis
      anterior (P<.01). Greater activation of the kicking limb iliacus (P<.01),
      gastrocnemius (P<.01), vastus medialis (P = .016), and hip adductors (P<.01)
      occurred during the instep kick. Significant differences were seen between the
      kicking limb and the support limb for all muscles during both types of kick.
      CONCLUSIONS: Certain lower extremity muscle groups face different demands during
      the soccer instep kick compared to the soccer side-foot kick. Similarly, the
      support limb muscles face different demands than the kicking limb during both
      kicks. Better definition of lower extremity function during kicking provides a
      basis for improved insight into soccer player performance, injury prevention, and
      rehabilitation.

PMID- 17549956
TI  - Eccentric training decreases paratendon capillary blood flow and preserves
      paratendon oxygen saturation in chronic achilles tendinopathy.
AB  - STUDY DESIGN: A controlled, randomized, prospective study, OBJECTIVE: To assess
      the changes in paratendon microcirculation after 12 weeks of daily painful
      eccentric training in individuals with chronic Achilles tendinopathy. BACKGROUND:
      Changes in tendon and paratendon microcirculation are evident in insertional and
      midportion Achilles tendinopathy. Whether the paratendon is involved in eccentric
      training response is not known. METHODS: Twenty patients with chronic Achilles
      tendinopathy were recruited for a prospective, controlled trial using eccentric
      exercise. A laser Doppler system assessed capillary blood flow (flow), tissue
      oxygen saturation (SO2), and postcapillary venous filling pressure (rHb) at 8
      paratendon locations at depths of 2 and 8 mm. RESULTS: Pain in the eccentric
      training group was reduced by 48% (from a mean of 4.1 +/- 2.9 to 2.1 +/- 2.2,
      P<.05). Deep paratendon blood flow decreased at the midportion paratendon
      location (P<.05). Superficial blood flow at the medial distal midportion position
      (by 31%, P = .008) and the lateral proximal midportion location (by 45%, P =
      .016) were significantly decreased postintervention, No significant change of
      superficial or deep paratendon oxygenation was found after intervention as
      compared to baseline. Deep paratendon postcapillary venous filling pressures were
      significantly reduced following eccentric training (P<.05). CONCLUSION: An
      eccentric-training program performed daily over 12 weeks reduced the increased
      paratendinous capillary blood flow in Achilles tendinopathy by as much as 45% and
      decreased pain level based on a visual analog scale. Local paratendon oxygenation
      was preserved while paratendinous postcapillary venous filling pressures were
      reduced after 12 weeks of eccentric training, which appears to be beneficial from
      the perspective of microcirculation.

PMID- 17549957
TI  - [Cervical hematoma after discectomy for spondylosis. An indication of urgent
      tracheotomy].
AB  - We report the clinical case of a hematoma after surgery of cervical spondylosis
      which required an urgent tracheotomy due to failure in the orotracheal
      intubation. This illness in advanced degree, so called cervical spondylotic
      myelopathy, is the most serious consequence of cervical intervertebral disc
      degeneration.

PMID- 17549958
TI  - [Inverted papilloma. Review of 23 cases].
AB  - Inverted papilloma is a benign sinonasal tumour with a high recurrence rate and
      its treatment must be surgery, using endonasal surgery or external aproach. We
      present a retrospective study of 23 cases treated in our center from 1988 to
      2003. There were 15 males and 8 females with a mean follow-up of 6 years. The
      recurrence rate was 40.9%. Patients who underwent endonasal surgery had a
      recurrence rate of 36.6%, and those who underwent external aproach surgery had a
      recurrence rate of 45.5%. There was a 4.5% of association with carcinoma.
      Endonasal surgery might be a valid surgery aproach for the treatement of inverted
      papilloma in selected cases.

PMID- 17549959
TI  - [Nasoalveolar cyst. Five new cases].
AB  - Nasoalverolar cyst are nonodontogenic maxillary cysts, rare and benign, which are
      more common in females and blacks. Their diagnosis can be established mainly on
      the clinical presentation, being usually asymptomatic during several years until
      they are large enough to cause cosmetic deformities and/or nasal obstruction,
      with asymmetrical alar flare. The treatment of choice is the complete surgical
      excision via a sublabial approach. Five cases diagnosed and treated at the Santa
      Maria del Rosell Hospital are reported, describing the most relevant clinican and
      pathological findings, so the diagnostic ant therapeutic methods.

PMID- 17549960
TI  - [Morphology of the parathyroid glands. A study of 146 samples and review of the
      literature].
AB  - Parathyroid hyperfunction condition has a very diverse and unspecific symptoms
      and signs. We have performed an anatomopathologic study of 146 parathyroid gland
      from patients diagnosed from hyperparathyroidism. About a 72.6% of the patients
      presented a parathyroid adenoma while in the rest 27.4% it was observed principal
      cells hyperplasia. Up to now we have not registered any cases of parathyroid
      carcinoma after anatomopathological exam of the removed gland. The mayority of
      the adenomas (85%) were found on the lower parathyroids and its size varied
      between 6 mm and 5 cm. In one case an double adenoma was diagnosed and in another
      two cases the adenoma was located in the superior mediastine.

PMID- 17549961
TI  - [Otolaryngologist approuch of tumors of mid-line location. A case study].
AB  - Congenital tumors of midline location are infrequent. Their highest incidence is
      before 3 years old. They can be localized on the surface of the skin or have a
      connection to the central nervous system. The diagnosis can be established by
      clinical examination, image study and biopsy. The present study describes the
      clinical case of a six year old boy with a fast growing swelling, located close
      to the inner orbit of the right eye and off the mid-nasal line. The diagnosis was
      established by TC (computerized axial tomography) as well as FNAB (fine needle
      aspiration biopsy), concluding it was a dermoid cyst. Literature was revised
      focusing our attention on the way of appearance, differential diagnosis and
      possibilities of treatment for these tumors.

PMID- 17549962
TI  - [Cutaneous melanoma of the head and neck].
AB  - The clinical records of 20 patients with the diagnosis of cutaneous melanoma of
      the head and neck treated between 1991 and 2005 were retrospectively reviewed.
      Advances in diagnostic techniques and treatment have had obvious impact on
      outcomes in cutaneous melanoma. Cutaneous melanoma of the head of neck is treated
      with complete surgical resection in early stage disease. Resection margins are
      determined by the size and depth. Evaluation for regional and distant metastatic
      disease is necessary in advanced stage disease. Adjuvant therapy may be indicated
      in regional nodal disease.

PMID- 17549963
TI  - [Parotid tuberculosis simulating neoplasia. Presentation of a case and review of
      literature].
AB  - A case ofparotid tuberculosis (PTB) that during its clinical presentation
      complementary proofs, exploration and realised treatment made suspect as first
      possibility a parotid tumor is presented. After an histologic study, it could be
      proved that the real problem of the patient was that she had suffered a parotid
      tuberculosis. An exposition of the case is made with the different technics that
      must be realised facing a patient of these caracteristics, before thinking in
      surgery, although secure, but with its mortal risks in these times where the
      incidence of tuberculosis is increasing in the first world.

PMID- 17549964
TI  - [Achondroplasia, judgement about the upper airway approach].
AB  - Achondroplasia is an hereditary disorder which belongs to the group of illnesses
      called condristrophic or anomalies in the ossification of the cartilages. Its
      main characteristic is a series of irregularities in the skeleton, but the most
      outstanding characteristic is the short height. The diagnosis of achondroplasia
      is achieved by means of a combination of clinical and radiological
      characteristics. The 99% of the cases is diagnosticated by the genetic study.
      Because of its multiple deformities not only in the skull and cervical but also
      thoracic, usually in adults, it means a challenge for the use of upper airway
      when it's requiered. To choose the fibreoptics or orotraqueal intubation or the
      tracheotomy are very complex processes in these cases. We do a revision about the
      ENT aspects to be considered in the patients of achondroplasia

PMID- 17549965
TI  - [History of the tonsil surgery].
AB  - Tonsillectomy is one of the more frequent surgical techniques in the
      otolaryngological practice. In the first century A. D., Cornelius Celsus in Rome
      described the removal of the tonsils. Since them, devices used for tonsillectomy
      included a wide variety of instruments as snares, guillotines, scalpels ("cold"
      and ultrasonic), forceps and lasers. Likewise, the improvement of the anesthetic
      procedures and the perioperative management have contributed greatly to success
      with this surgical procedure. To sum up, the instruments and procedures used for
      tonsillectomy have evolved to render it a precise operation.

PMID- 17549966
TI  - [Diffuse large B-cells lymphoma of the parotid gland (MALT). Report of a case and
      review of the literature].
AB  - Althouh lymphomas are an illness that characteristically affects the lymph nodes
      they can present in other locations (extranodes). The lymphoid tissue of the
      salivary glands can be considered part of the called mucosa-associated lymphoid
      tissue (MALT). We report the case of a diffuse large B-cells parotid lymphoma.
      The location on the parotid gland, within its rareness, is the most common for
      salivary gland lymphomas whose diagnosis is always histological by examination of
      the removed piece since the biopsy can be nonsufficient and take to a wrong
      diagnosis besides the greater risk of injury on the facial nerve.

PMID- 17549967
TI  - Inflammatory myofibroblastic tumor of the larynx. Case report.
AB  - Inflammatory myofibroblastic tumors (IMT) of the larynx are uncommon lesions that
      easily may be misinterpreted as malignant epithelial or mesenchymal spindle cell
      neoplasms. When located in the upper airway, IMTs tend to be less aggressive, but
      have the potential for local invasion and recurrence. The authors describe a rare
      case of IMT in a 47 year old man, occurring in the vocal fold who underwent
      surgical treatment five times, because of its higher recurrence rate.

PMID- 17549968
TI  - 'If there are no lecturers, who will do the teaching'?

PMID- 17549969
TI  - A life change for the better.
AB  - The menopause can be a time of upheaval in a woman's life. But it can also be a
      wake-up call for them to think about their future health.

PMID- 17549970
TI  - Caring for children at home.
AB  - There are wide variations in the way children's palliative care needs are met in
      the community. Researchers are helping to improve services.

PMID- 17549972
TI  - In praise of worship.

PMID- 17549971
TI  - Standing firm.
AB  - Assertiveness is the ability to express clearly what you want, think or feel. It
      is as important in nurses' home lives as it is at work.

PMID- 17549973
TI  - Patients are our best allies.

PMID- 17549974
TI  - Effectiveness and safety of restraint and breakaway techniques in a psychiatric
      intensive care unit.
AB  - AIM: To evaluate the effectiveness and safety of restraint and breakaway in a 16
      bed psychiatric intensive care unit. METHOD: Analysis of specifically designed
      incident forms was undertaken to identify the effectiveness and safety of take
      downs and holds, in relation to staff numbers and gender composition of the
      restraint team; and identify the use, effectiveness and safety of breakaway
      techniques. FINDINGS: There was no evidence to suggest that having a greater than
      average number of staff involved in the restraint or the avoidance of female
      staff in limb management had a detrimental effect on effectiveness or safety of
      the restraint. Breakaway was used in 13% of attacks on staff and in 70% of these
      the intended purpose of the breakaway was achieved. CONCLUSION: Restraint
      procedures, as taught in Control and Restraint training, appear to be an
      effective and reasonably safe means of manually controlling a violent client in
      psychiatric intensive care settings.

PMID- 17549975
TI  - Euthanasia: the legal issues.
AB  - The legal status of euthanasia is frequently deliberated. It remains unlawful in
      Britain and advocates for a change in the law are vigorously opposed by those who
      argue that it should remain unchanged. An objective account, in which current law
      and arguments for and against change are exposed, is essential to inform the
      euthanasia debate. In this article the legal issues concerning euthanasia are
      examined and arguments raised by proposed changes in the law are considered.

PMID- 17549976
TI  - Practice-based assessment: strategies for mentors.
AB  - The reader is encouraged to investigate what is involved in the practice-based
      assessment of students and to consider how it might be improved. The author
      suggests that students should be assessed on their performance during episodes of
      care rather than by continuous assessment.

PMID- 17549977
TI  - Healthy diet and older people.

PMID- 17549978
TI  - Education in overdrive. Are you ready for the rapidly fusing worlds of learning
      and technology?

PMID- 17549979
TI  - Drug-eluting stents in primary angioplasty long-term clinical outcomes.
AB  - INTRODUCTION: The use of drug-eluting stents in the context of mechanical
      reperfusion following ST-segment elevation myocardial infarction (MI) was
      initially viewed with concern. The main fear was that the drugs' action in
      unstable lesions could increase the risk of thrombotic stent occlusion.
      Furthermore, there was no evidence that the proven benefit of reduced instent
      restenosis could be extended to such patients, since they were excluded from the
      initial clinical trials. OBJECTIVES: To assess the safety and long-term clinical
      outcomes of the use of drug-eluting stents in primary angioplasty. METHODS: The
      first 100 consecutive and non-selected patients admitted for MI and treated by
      primary angioplasty with drug-eluting stent implantation in the target lesion
      were analyzed retrospectively. The efficacy and safety of the procedure, in
      hospital clinical evolution and the occurrence of major adverse cardiac events in
      the first year were assessed. RESULTS: Patients' mean age was 58.2 +/- 11.5
      years, and 78 were male. The success rate of primary angioplasty was 99%. Stents
      coated with sirolimus were used in 67 patients, paclitaxel in 19 and
      dexamethasone in 16. In-hospital mortality was 3%. The follow-up rate at 12
      months was 98%. During this period, the rate of target vessel revascularization
      was 1% (with no patient requiring target lesion revascularization), MI 2%, and
      overall mortality 3.9%. Fourteen patients had clinical indication for repeat
      coronary angiography, which showed no significant in-stent restenosis. One event
      was considered to be due to acute stent thrombosis. The incidence of major
      adverse events was 5.9%. CONCLUSION: The use of drug-eluting stents in MI
      patients undergoing primary mechanical revascularization is safe and is
      associated with a reduced incidence of major adverse events, thrombosis and
      clinical restenosis at one year.

PMID- 17549980
TI  - Drug-eluting stents in ST-segment elevation myocardial infarction.

PMID- 17549981
TI  - Ambulatory blood pressure measurement in young normotensive patients with
      autosomal dominant polycystic kidney disease.
AB  - INTRODUCTION: Autosomal dominant polycystic kidney disease (ADPKD) is the most
      common genetic disorder causing chronic kidney disease in adults. Hypertension
      occurs early and frequently precedes the development of renal failure. It has
      been shown that clinically normotensive young adults with ADPKD exhibit increased
      left ventricular mass and left ventricular mass index (LVMI), which contributes
      to the increased cardiovascular risk in these patients. We set out to investigate
      whether normotensive patients have a prehypertensive state that could account for
      their increased LVMI. METHODS: Patients with ADPKD followed as outpatients were
      selected if they were aged between 21-30 years, were normotensive (office and
      sporadic blood pressure < 140/90 without medication), and had normal renal
      function (GFR > 90 ml/min). Normotensive controls aged between 21-30 years were
      selected, all with normal renal ultrasound, serum creatinine, dipstick analysis
      and microalbuminuria /creatinine ratio. Patients and controls underwent 24-hour
      ambulatory blood pressure measurement (ABPM) according to the local protocol.
      RESULTS: Systolic (124.7 +/- 7.6 vs. 115.2 +/- 6.9; p < 0.0001), diastolic (77.3
      +/- 6.3 vs. 70.5 +/- 3.9; p < 0.0001) and mean (92.7 +/- 8.5 vs. 85.7 +/- <
      0.001) 24-hour blood pressure was significantly higher in patients with ADPKD
      compared to controls. Statistically significant differences were also found when
      daytime and night-time periods were analyzed separately. Hypertension on ABPM was
      diagnosed in 6 patients but differences in the ABPM profile persisted even when
      these patients were excluded from the analysis. CONCLUSION: In young adults with
      ADPKD there is a prehypertensive state that can be detected using ABPM.

PMID- 17549982
TI  - Magnetic resonance imaging findings in suspected arrhythmogenic right ventricular
      dysplasia.
AB  - INTRODUCTION: Cardiac magnetic resonance imaging (CMRI) has been used to evaluate
      right ventricular morphology in suspected arrhythmogenic right ventricular
      cardiomyopathy (ARVC). We report qualitative CMRI findings in patients with
      suspected ARVD. METHODS: A retrospective review of images in 35 patients referred
      for CMRI with clinically suspected ARVD. RESULTS: Eleven patients were considered
      to have alterations on CMRI. In 5 patients a dilated outflow tract and/or right
      ventricle was identified; a high intramyocardial T1 fat signal was identified in
      one patient, regional dyskinesia in two patients, and small excavated pouches in
      4 patients. Prominent right ventricular trabeculae were present in 4 patients.
      CONCLUSIONS: CMRI alterations used for diagnosis of ARVC were identified in
      approximately one-third of patients referred to our center with either clinical
      suspicion or diagnosis of ARVC.

PMID- 17549983
TI  - Exercise-induced left ventricular outflow tract obstruction. A potential cause of
      symptoms in the elderly.
AB  - We describe a 79-year-old male patient with no significant risk factors for
      coronary heart disease besides age and gender. He was referred for cardiology
      consultation because of effort dyspnea. Diagnostic exams including laboratory
      tests, chest X-ray, ECG and resting echocardiogram showed no abnormalities. He
      underwent exercise stress echocardiography, which revealed reduced exercise
      tolerance and a dynamic left ventricular outflow tract obstruction with an
      intraventricular gradient of over 50 mmHg. No segmental wall motion abnormalities
      were observed. He was treated with the beta-blocker bisoprolol 5 mg qd, with
      significant clinical improvement. Two years later exercise stress
      echocardiography was repeated and better functional capacity was apparent, with
      no intraventricular gradient during peak exercise. The authors discuss the
      clinical importance of this unsuspected cause of symptoms in the elderly.

PMID- 17549984
TI  - Stress cardiomyopathy in thromboembolic arterial disease.
AB  - Apical ballooning is a novel clinical entity reported in different contexts of
      physical and psychological stress, which is more common in middle-aged women. Of
      unknown etiology, the syndrome is characterized by a sudden and transient
      dilatation of the left ventricular apex in the absence of obstructive
      atherosclerotic coronary disease or evidence of myocardial necrosis, with total
      late recovery of ventricular function. The authors report the case of a 53-year
      old woman who was admitted to the emergency room with left arm ischemia and low
      cardiac output, requiring ventilatory support. Left catheterization showed
      typical medial and apical myocardial dysfunction, with normal coronary arteries.
      Transesophageal echocardiography revealed a thrombus attached to the lower face
      of the aortic arch, which probably explained the thromboembolism of the arm but
      was unlikely to be the cause of the left ventricular dysfunction since there were
      no enzymatic or electrocardiographic signs of myocardial necrosis and normal wall
      motion was fully recovered.

PMID- 17549985
TI  - Diet, atherosclerosis and atherothrombotic events.
AB  - Epidemiologic studies and clinical trials have shown that diet and, in
      particular, the consumption of fats, influence the body's metabolism and can
      affect the development of atherosclerosis and resulting cardiovascular
      repercussions. A Western-type diet (high in saturated fats, simple sugars and
      salt, and low in fish, vegetables and fiber) has been associated with
      proinflammatory, pro-oxidative and prothrombotic tendencies and consequently
      higher cardiovascular risk. By contrast, a Mediterranean-type diet (with less
      meat and more fish, fiber, fruit, vegetables, olive oil and wine) appears to
      explain the lower tendency for cardiovascular disease (and cancer) in those who
      consume it. Between these two are population groups who prefer diets rich in
      polyunsaturated fatty acids. The lack of randomized and rigorously controlled
      population and clinical trials relating types of diet to primary or secondary
      cardiovascular events may explain some of the disagreements surrounding this
      subject. It would also explain the lack of results that shed light on diet
      dependent mechanisms that may affect the development of atherosclerosis. In
      general, it is accepted that the morphologic and functional characteristics of
      vascular endothelium are influenced by the components absorbed from the diet.
      Prolonged exposure to certain harmful components in the diet may increase the
      risk of endothelial dysfunction, as shown by a decrease in antithrombotic,
      antioxidative, antiinflammatory and peripheral vasodilatory modulators, which
      represents the first step towards the onset of atherosclerosis. Among the main
      mechanisms involved in endothelial dysfunction are the proinflammatory and
      prooxidative effects of excess cholesterol, in contrast with the apparent benefit
      of monounsaturated fatty acids and the less consistent results obtained with
      polyunsaturated fatty acids.

PMID- 17549986
TI  - Anomalous origin of the right coronary artery diagnosed by cardiac computed
      tomography.

PMID- 17549987
TI  - Magnetic resonance imaging findings in non-compaction of the left ventricle.

PMID- 17549988
TI  - [Medical optics--perspectives].

PMID- 17549989
TI  - [Selective Retina Therapy (SRT)].
AB  - Selective Retina Therapy (SRT) is a new and very gentle laser method developed at
      the Medical Laser Center Lubeck. It is currently investigated clinically in order
      to treat retinal disorders associated with a decreased function of the retinal
      pigment epithelium (RPE). SRT is designed to selectively effect the RPE while
      sparing the neural retina and the photoreceptors as well as the chorioidea. Aim
      of the therapy is the rejuvenation of the RPE in the treated areas, which should
      ideally lead to a long term metabolic increase at the chorio-retinal junction. In
      contrast to conventional laser photocoagulation, which is associated with a
      complete thermal necrosis of the treated site, SRT completely retains full
      vision. This paper reviews the methods and mechanisms behind selective RPE
      effects and reports the first clinical results. An online dosimetry technique to
      visualize the ophthalmoscopically invisible effects is introduced.

PMID- 17549990
TI  - [Adaptive estimation of contrast thresholds using the visual evoked potential
      (VEP)].
AB  - The visual evoked potential (VEP) can be used to objectively estimate sensory
      thresholds. Recently, we developed an adaptive procedure for this threshold
      estimation based on a Fourier analysis of steady-state responses during the
      recording. In this study we quantified the reduction in recording time of this
      adaptive procedure. Steady-state VEPs to pattern reversal (f = 8.3 Hz) of
      checkerboards with 8 contrast values between 0.64% and 82% were recorded
      monocularly. Adaptive and non-adaptive recordings were performed for full
      correction (fc) and for blurred stimulus patterns (+1.5 D and +3.0D). VEP
      contrast thresholds were defined by the lowest contrast condition that showed a
      significant response. An ANOVA of the VEP thresholds showed significant effects
      (p < 0.0001) of the factors "procedure" (psychophysics, adaptive VEP, non
      adaptive VEP) and "correction" (fc, fc + 1.5D, fc + 3.0D). Compared to non
      adaptive recordings, adaptive recordings showed thresholds that were
      significantly reduced and closer to psychophysical contrast thresholds. By
      applying the adaptive procedure the recording time can be reduced by a factor of
      about 2 when compared to the non-adaptive procedure. The new adaptive VEP
      procedure may help to improve the correlation of electrophysiological and
      psychophysical estimates of sensory thresholds and may accelerate functional
      testing in the clinical routine.

PMID- 17549991
TI  - [Optical coherence tomography by evaluation of the spectral modulation of white
      light interferometry].
AB  - Amplitude and phase factor of a wave scattered from an object relative to the
      amplitude and phase factor of the incident wave reveals the spatial distribution
      of the object's scattering power by means of Fourier transform. In this paper
      this relation is discussed and the dependence of the spatial resolution and the
      maximal range of depth on the physical parameters as well as the influence of
      dispersion are investigated. The signal-to-noise ratio yields a measure on the
      sensitivity of the method which is put into relation of the sensitivity of Time
      Domain Optical Coherence Tomography (TD-OCT). A white light interferometer is
      discussed. The spectrum of the interference between the wave scattered at an
      object and the reference wave is observed and yields the spectral distribution of
      the relative amplitude and phase factor.

PMID- 17549992
TI  - [Preoperative intraocular lens power calculations in problem eyes].
AB  - The removal of the opaque crystalline lens in cataract surgery and its
      replacement by an artificial lens has become the most successful surgical
      intervention in the history of medicine. Modern intraocular lenses, today's micro
      incision approach and high-end measurement and computational techniques provide
      restoration of good visual acuity in the majority of cases. Patients with problem
      eyes not allowing standard procedures for intraocular lens power calculation
      require special attention. Among them are highly ametropic subjects with very
      short or long eyes or patients, whose corneal structures are different from
      normal due to preceding refractive surgery. The special problems for measurement
      and lens power calculations in these eyes are dealt with in detail. Based on
      hitherto unpublished clinical data, causes and possible solutions for the
      existing problems are discussed. Generally, the best available measurement
      techniques should be applied in these cases. With respect to the algorithms used
      it has to be made sure that no additional errors are introduced by the algorithms
      themselves. The popular SRK II formula should therefore not be used any more. If
      errors are minimized this way, gross postoperative refractive surprises should be
      avoided even in problem eyes.

PMID- 17549993
TI  - [Spectacle lenses in sports: optimization of the imaging properties based on
      physiological aspects].
AB  - The goal of correction spectacles is to create a sharp image on the retina by the
      combined optical system of the eye and the spectacle lens for a given ametropia.
      As a matter of principle, in this optical system an aberration free correction
      can be achieved in the optical centre of the spectacle lens, but not over the
      entire range of gaze angles. In spectacle optics large angles play an important
      role, different from paraxial optics where only rays close to the axis with small
      angles of incidence are relevant. This generates additional aberrations, the so
      called oblique astigmatism, which can only be compensated at the expense of the
      spherical power. Therefore, every spectacle lens represents apart from the main
      visual point-, a more or less good compromise. For sports lenses in the currently
      used curved frames, an additional challenge arises from the fact that their
      orientation in front of the eye is generally not perpendicular to the principal
      gaze direction but tilted. In this article the imaging properties of such tilted
      sports lenses are discussed, and it is described why this results in a minor
      quality without a specific consideration of the obliqueness. The fact that tilted
      sports spectacles are also able to possess an improved correction behaviour for
      all gaze angles is due to individual mathematical optimization methods. The aim
      of the present article is, based on the underlying physical and physiological
      effects, to point out the advantages of individually optimized sports spectacle
      lenses in comparison to tilted lenses generated without applying this
      sophisticated computational method.

PMID- 17549994
TI  - [Image diagnostic of the retina with fundus cameras].
AB  - Imaging of the retina of the human eye is an essential aid for medical diagnosis.
      The technical realization of photos of the ocular fundus is not trivial because
      of the optical properties of the eye. Established devices to obtain images are so
      called fundus cameras with digital documentation capabilities. New procedures do
      not need the use of pupils enlarging measures at the patient and work with
      infrared illumination. The quality of the diagnostic findings depends on the one
      hand fundamentally on the lay-out of the optical design of the fundus camera. On
      the other hand there are limitations caused by the eye itself which is always a
      part of the beam path. Both impacts define the attainable results. Special
      applications deal with the stereoscopic imaging of the retina or with spectral
      reflection characteristics.

PMID- 17549995
TI  - How has the NHS fared under Blair?

PMID- 17549996
TI  - Supporting nurses in need.

PMID- 17549997
TI  - Mind over matter.
AB  - A pioneering unit in Cambridgeshire is helping people with brain injury by taking
      a pragmatic approach to their long-term difficulties. Their work is now creating
      interest and changing practice in Russia.

PMID- 17549998
TI  - At last I have my life back.
AB  - Bethann Siviter needed support and specialist equipment to return to work after
      her illness. It has been a learning curve for all involved.

PMID- 17549999
TI  - Don't forget dad.
AB  - Fathers of disabled children can feel left out of care decisions. But the charity
      Contact a Family is aiming to bridge the gap by putting them in touch with each
      other and providing support for health professionals.

PMID- 17550000
TI  - Words of wisdom.
AB  - When we feel that something is not right or is unsatisfactory in our lives,
      counselling can help us come to an understanding of the problem and its personal
      meaning.

PMID- 17550001
TI  - Read all about it--operation cancelled.

PMID- 17550002
TI  - Cognitive behavioural therapy for risk management in schizophrenia.
AB  - This article proposes that cognitive behavioural therapy--as recommended by the
      National Collaborating Centre for Mental Health (2002)--can be used to form part
      of a risk management strategy for people diagnosed with schizophrenia. This may
      be a more effective and acceptable intervention because of its collaborative
      nature. The article includes case studies from practice to illustrate strategies
      that can be used.

PMID- 17550003
TI  - Improving health care through payment by results.
AB  - Nursing faces new opportunities and challenges as part of the government's
      initiative to introduce Payment by Results. These opportunities arise from
      increasing demands to work effectively in an environment of intensive customer
      demand and expectation. The challenge for all nurses is to continue to deliver
      quality health care while keeping pace with changes to services and
      organisational responsiveness. It is important that nurses and other health
      professionals ensure that the needs of patients are not compromised in the
      pursuit of financial reward and that systems of work are improved as part of this
      initiative.

PMID- 17550004
TI  - Ethics of abortion: the arguments for and against.
AB  - In England, Scotland and Wales legislation has facilitated the process of
      procuring an abortion to the point at which, in 2007, it appears to have been
      effectively assimilated into contemporary life. However, despite the legal
      acceptance of abortion it remains an ethically contentious subject. Arguments in
      favour of, or in opposition to, abortion can arouse vociferous and, on occasions,
      extreme reactions. At the heart of the abortion debate lie questions concerning
      rights, autonomy and the way in which society views disability (if a pregnancy is
      terminated for this reason alone). It is important that health professionals
      comprehend the basis of the abortion debate, from the perspective of their
      profession, society as a whole and the individual woman who may have had or is
      considering an abortion or has been affected by the subject in some way. This
      article examines some of the key ethical issues concerning abortion.

PMID- 17550005
TI  - Recognition and management of patients with anaphylaxis.
AB  - Anaphylaxis is a severe and potentially fatal systemic allergic reaction. It
      requires rapid recognition, treatment and management by health professionals.
      With their rapid onset and multiple organ involvement, anaphylactic reactions are
      a medical emergency. Therefore, health professionals must have a good
      understanding of the condition and be able to identify symptoms promptly to
      follow the treatment guidelines provided by the Resuscitation Council (UK).

PMID- 17550006
TI  - Chronic diarrhoea.

PMID- 17550007
TI  - No barriers to nursing.

PMID- 17550008
TI  - 'Judge me on my work'.

PMID- 17550009
TI  - Knowledge is power.

PMID- 17550010
TI  - [Children develop through confidence].

PMID- 17550011
TI  - [Male circumcision protects against HIV/AIDS. But the question is if it can be a
      significant part of the prevention].

PMID- 17550012
TI  - [ADHD difficult to diagnose in adults. ASRS v1.1 Self-Report Scales valuable help
      -now translated to Swedish].

PMID- 17550013
TI  - [Possible connection between eating disorders and ADHD. Bulimia can relieve ADHD
      symptoms, central nervous stimulants are of good help].

PMID- 17550014
TI  - [Those who themselves choose bariatric surgery are the most suitable candidates.
      The intervention requires life-long adaptation, important to check if the patient
      is upp to it].

PMID- 17550015
TI  - [Does alcohol drinking induce overweight? No scientific clear-cut-answers].

PMID- 17550016
TI  - [Dyspepsia and reflux. Systematic literature review from SBU].

PMID- 17550017
TI  - [Male circumcision is not medically justified].

PMID- 17550018
TI  - [The most vulnerable addicts deserted by the National Board of Health and
      Welfare].

PMID- 17550019
TI  - [Bladder calculi in a medieval man--an unusual archeological finding].

PMID- 17550020
TI  - [New international consensus document on peripheral arterial disease. TASC II for
      improved care].

PMID- 17550021
TI  - [Ear thermometer not an adequate alternative to rectal thermometer. A comparative
      study shows big temperature discrepancies of ear temperature measurements ].

PMID- 17550022
TI  - [Severe abdominal pain and hyponatremia was acute intermittent porphyria].

PMID- 17550023
TI  - [Orthopedic care varies over the country].

PMID- 17550024
TI  - [Musculoskeletal diseases].

PMID- 17550025
TI  - [Shoulder diseases].

PMID- 17550026
TI  - [Lumbar diseases].

PMID- 17550027
TI  - [Diseases of the hip and knee joints].

PMID- 17550028
TI  - [Injuries of the menisci and the cruciate ligaments].

PMID- 17550029
TI  - [Foot diseases].

PMID- 17550030
TI  - [Systemic amyloidoses--new treatment methods make early and exact diagnosis more
      and more important].

PMID- 17550031
TI  - [Hyperprolactinemia induced by neuroleptics].

PMID- 17550032
TI  - [Psychiatry must cooperate with other care services in a better way].

PMID- 17550033
TI  - [Weak evidence for morphine in chronic pain].

PMID- 17550034
TI  - [Unsuitable to recommend special silk textile as alternative to cortisone in
      atopic eczema].

PMID- 17550035
TI  - [The patient's choice shows the way].

PMID- 17550036
TI  - [Aluminum allergy following vaccination should be entitled to compensation as
      drug-induced injury].

PMID- 17550037
TI  - Effect of carbonated beverages, coffee, sports and high energy drinks, and
      bottled water on the in vitro erosion characteristics of dental enamel.
AB  - PURPOSE: This study evaluated the effect of carbonated and non-carbonated
      beverages, bottled and tap water, on the erosive potential of dental enamel with
      and without fluoride varnish protection. MATERIALS AND METHODS: Beverages used in
      this study included: Coca Cola Classic, Diet Coke, Gatorade sports drink, Red
      Bull high-energy drink, Starbucks Frappuccino coffee drink, Dasani water
      (bottled), and tap water (control). Enamel surfaces were coated with Cavity
      Shield 5% sodium fluoride treatment varnish. Twenty-eight previously extracted
      human posterior teeth free of hypocalcification and caries were used in this
      study. The coronal portion of each tooth was removed and then sectioned
      transverse from the buccal to lingual surface using a diamond coated saw blade.
      The crown sections were embedded in acrylic resin blocks leaving the enamel
      surfaces exposed. The enamel surfaces were polished using 600 to 2000 grit
      abrasive paper and diamond paste. Test specimens were randomly distributed to
      seven beverage groups and comprised 4 specimens per group. Two specimens per
      beverage group were treated with a fluoride varnish while 2 specimens did not
      receive fluoride coating. Surface roughness (profilometer) readings were
      performed at baseline (prior to fluoride treatment and immersion in the beverage)
      and again, following immersion for 14 days (24 hours/day). The test beverages
      were changed daily and the enamel specimens were immersed at 37 degrees C.
      Surface roughness data was evaluated using multiple factor ANOVA at a
      significance level of p<0.05. RESULTS: Results showed that Coca-Cola Classic,
      Gatorade and Red Bull with/without fluoride revealed the highest post-treatment
      surface roughness measurements. Coca-Cola Classic, Diet Coke, Gatorade, and Red
      Bull all showed significantly higher post treatment readings than StarBucks
      coffee, Dasani water, and tap water. Fluoride varnish was not a significant
      impact factor; however, beverage (type) and exposure time were significant impact
      variables. CONCLUSION: Both carbonated and non-carbonated beverages displayed a
      significant erosive effect on dental enamel; however, fluoride varnish treatments
      did not demonstrate a significant protective influence on enamel surfaces.

PMID- 17550038
TI  - Do our children play safe?
AB  - Sports participation is a frequent cause of injury in general to children and
      adolescents. 719 athletically active school children belonging to the age group
      of 11-14 years were selected from the four urban localities in south India (i.e,
      Bangalore Chennai, Cochin & Hyderabad). Data was collected by a well structured
      questionnaire. The results revealed that the south Indian urban school children
      had inadequate levels of awareness regarding orofacial injuries and their
      emergency care. The knowledge regarding protective devices was found to be
      minimal. Majority of the children were aware of mouthguards but their usage was
      nil.

PMID- 17550039
TI  - A comparative evaluation of the fracture strength of pulpotomized primary molars
      restored with various restorative materials.
AB  - Sixty extracted primary molars were used in the study. After pulpotomy, these
      were divided into four groups on the basis of restorative materials to be used.
      Results showed that the Ormocer had the maximum fracture strength while the
      posterior Glass Ionomer Cement showed the least fracture strength among the
      various restorative materials used in the study.

PMID- 17550040
TI  - The effectiveness of vitamin "E" in the treatment of oral mucositis in children
      receiving chemotherapy.
AB  - The aim of this study was to study the effect of vitamin "E" in the treatment of
      oral mucositis. 80 patients with oral mucositis were randomly distributed into 2
      groups: group A, topically applied vitamin "E" and group B, vitamin "E" was given
      systemically. The 2 groups were evaluated for 5 days. Results showed that in
      group A grades of oral mucositis improved significantly, while in group B no
      significant improvement was noticed. It is concluded that topical application of
      100 mg vitamin "E" twice daily is an effective measure for the treatment of
      chemotherapy-induced oral mucositis.

PMID- 17550041
TI  - Tooth supported prosthetic rehabilitation in a 5-year-old child with early
      childhood caries.
AB  - This paper reports the case of a 5-year-old patient with early childhood caries
      (ECC) and presents an alternative prosthetic treatment with a tooth-supported
      overdenture. Primary canines were endodontically treated and received
      intraradicular posts with ball-type attachments to attach a tooth-supported
      overdenture. The patient was followed for 18 months both clinically and
      radiographically. In addition to esthetic and functional oral rehabilitation, the
      prosthetic treatment had an important psychological impact on recovery of
      patient's self-esteem.

PMID- 17550042
TI  - Integrating dental screening and fluoride varnish application into a pediatric
      residency outpatient program: clinical and financial implications.
AB  - Delivery of preventive oral health services (POHS) has been embraced by many
      pediatric andfamily medical practices in North Carolina (NC). The outcome of
      implementing a state-wide Medicaid-supported oral health prevention initiative,
      "Into the Mouth of Babes Varnish and Screening Program (IMB), in an academic
      medical residency setting is described Retrospective chart audit of
      encounterforms and collection of administrative records related to POHS provided
      by pediatric medical residents for Medicaid recipients less than 3 years of age
      at the University of North Carolina pediatric continuity care clinic over 31
      months were examined A total of 1,081 visits and 655 patients were documented
      during the study period accountingfor 36.6% of all children aged 6-36 months seen
      in the clinic during the period of this study. Thirty-eight percentof the
      patients received one or more IMB follow-up visits. Twenty-nine (4.4%) children
      were reported to have one or more carious teeth and 94 children (14.1%) were
      referred to a dentist. The IMB program provides an oral screening, parent oral
      health counseling and application of fluoride varnish to the teeth at the medical
      appointment by non-dental personnel. Following a cost/revenue analysis it was
      concluded that a preventive oral health initiative in an academic setting
      provides an additional access to oral health preventative services for
      underserved children and contributes to the financial viability of the clinic.

PMID- 17550043
TI  - Effect of formaldehyde on rat liver in doses used in pulpotomies.
AB  - Many studies have questioned the toxic effects of formocresol, one of which is
      its systemic distribution. This study focused on determining whether there was
      risk of acute hepatic lesion after the use of intravenous formaldehyde in doses
      for multple pulpotomies in rats. Histological and biochemical changes were
      evaluated. Results showed that very high doses of formaldehyde injected into
      rats, doses that were much higher than those given for multiple pulp treatments
      in a single session in Pediatric Dentistry, showed no signs of liver toxicity.

PMID- 17550044
TI  - Comparison of three conscious sedation regimens for pediatric dental patients.
AB  - The aim of this study was to compare the clinical success of three conscious
      sedation regimens for pediatric dental patients. A clinical trial was performed
      wherein dental treatment was administered to pediatric patients ASA I and II
      under conscious sedation.. Fifty-four children were divided into three groups of
      18 patients each, randomly assigned Group A received hydroxyzine (2 mg/kg 2 h
      before treatment and a subsequent dose of 1 mg/kg 20 min before treatment)
      orally; group B received 0.50 mg/kg midazolam mixed with 1.5 mg/kg hydroxyzine 20
      min before treatment orally; group C received chloral hydrate, 50 mg/kg mixed
      with 1.5 mg/kg hydroxyzine 20 min before treatment orally. The Ohio State
      Behavioral Rating Scale (OSBRS) showed statistically significant differences
      between groups B and C with respect to group A. The regimens of midazolam or
      chloral hydrate mixed with hydroxyzine represent excellent choices for conscious
      sedation regimens for pediatric dental patients.

PMID- 17550045
TI  - Chemical versus conventional caries removal techniques in primary teeth: a
      microhardness study.
AB  - The aim of this in vitro study was to assess the remaining dentinal surface after
      carious tooth tissue removal with a low speed conventional bur and two
      chemomechanical methods, (Papacarie and Carisolv), using the microhardness test.
      It was concluded that the hardness of the remaining dentin after carious tissue
      removal was lower than that obtained on healthy dentin, without significance
      between the different means of carious tissue removal (p<0.05).

PMID- 17550046
TI  - Evaluation of antimicrobial efficacy of various root canal filling materials used
      in primary teeth: a microbiological study.
AB  - The primary goal of endodontic treatment in primary teeth is to eliminate
      infection, and to retain the tooth in a functional state until their nornal
      exfoliation time without endangering the permanent dentition or the general
      health of the child. The complexity of the pulp canal system in primary teeth
      presents a discerning problem for chemo-mechanical preparation. One of the
      factors determining the success of endodontic treatment in infected primary teeth
      is the sealing material that should encompass among other factors a potent
      bactericidal effect and the capacity to resorb along with the roots of primary
      teeth. This study evaluated the antimicrobial effectiveness of 5 root canal
      filing materials and a negative control agent against 23 strains of bacteria
      isolated from infected root canals of primary molar teeth and 3 non standard
      bacterial strains using agar diffusion assay. The materials were Zinc oxide and
      Eugenol (ZOE), Zinc oxide-Eugenol and Formocresol (ZOE+FC), Calcium hydroxide and
      sterile water (CAOH+H2O), Zinc oxide and Camphorated phenol (ZO+CP), Calcium
      hydroxide and Iodoform (Metapex) and Vaseline (Control). All the materials except
      Vaseline showed varied antimicrobial activity against the test bacteria. The
      zones of inhibition were ranked into 4 inhibition categories based on the
      proportional distribution of the data. All the 26 bacterial isolates were
      classified under 4 groups based on Aerobic/Anaerobic and Gram positive/Gram
      negative. Statistical analysis was carried out to compare the antimicrobial
      effectiveness between materials tested with each of the bacterial groupings.
      ZOE+FC produced strong inhibtion against most bacteria when compared to ZOE,
      ZO+CP and CAOH+H2O. Metapex and Vaseline were found to be non inhibitory

PMID- 17550047
TI  - Artificial plaque removal with Carisolv system: a clinical approach.
AB  - In the present study, removal of artifcial plaque in pits and fissures with the
      Carisolv system was compared with that of conventional bristle brush methoda in
      vitro. The results indicate that in the dental clinic, complete plaque removal
      with the Carisolv is possible, and in addition to acid etching, treated cavity
      was almost free of debris which might increase sealant retention.

PMID- 17550048
TI  - Short resin-posts bonding to primary dentin. Microleakage and micro-morphological
      in vitro study.
AB  - The aim of this in vitro study was to evaluate the adhesion of two bonding
      systems (Single Bond and Adper Prompt L Pop, 3M ESPE) to short resin posts in the
      root dentin of primary teeth. Statistical analysis (Mann Whitney) revealed that
      there were no statistically significant differences between the materials (p=
      0.75), but the Single Bond group presented a wider resin-dentin inter-diffusion
      zone (RDIZ). Both groups showed long resin tags. It was concluded that although
      Single Bond produced a wider adhesive interface than Adper Prompt L Pop, leakage
      levels occurred in both systems.

PMID- 17550049
TI  - A case of submandibular gland mucocele.
AB  - Submandibular Gland Mucocele:The mucocele occuring in the submandibular region is
      rare, most cases originate in the sublingual gland. Here, we report a rare case
      of mucocele originating in the submandibular gland. In this report, we present
      such a case in a 7-year-old boy, who was treated by an extirpation of cyst with
      submandibular and sublingual gland

PMID- 17550050
TI  - Dental health status in children with acute lymphoblastic leukemia.
AB  - Acute Lymphoblastic Leukemic (ALL) children were selected to evaluate the dental
      health status from Regional Cancer Centre, Kerala. A 12 item questionnaire was
      distributed to all selected 104 children's parents who were present in the
      hospital and the children's oral cavity was examined. The results revealed
      moderate gingival inflammation in most of the samples irrespective of treatment.
      Tenderness on temporo mandibular joint, oral mucositis, high DMFT values were
      observed in children who were under treatment. History of halitosis before
      diagnosis of ALL was a predominant feature in a statistically significant number
      of children.

PMID- 17550051
TI  - Treatment of unilateral buccal crossbites in the primary, early mixed, and
      permanent dentitions: case reports.
AB  - It is important to recognize the development of an arch-width problem in
      pediatric patients and to determine the best time to treat it. One of these
      conditions is the posterior (buccal) crossbite where one may also find an
      exaggerated overjet, caused by maxillary excess, and/or mandibular width
      deficiency. One may also find a mandibular midline deviation on the side of the
      crossbite, creating a long-term orthopedic problem with a mild facial asymmetry.
      When correction of this condition is attempted in adulthood a poor results can be
      expected making this the most important reason for early treatment. Six clinical
      cases are presented, along with the mechanics performed in both arches.

PMID- 17550052
TI  - Developmental changes of pharyngeal airway structures from young to adult
      persons.
AB  - This cross-sectional study investigated developmental changes of pharyngeal
      airway structures. The materials were comprised of 120 lateral cephalometric
      radiographs and were divided into three stages according to the dental age.
      Results indicated that the upper pharyngeal depth increased with age, whereas,
      the lower pharyngeal depth was established early in life. The pharynx increases
      its capacity predominantly by vertical expansion. The developmental changes in
      pharyngeal structures were signficantly greater in males than in females.

PMID- 17550053
TI  - Anemia in cancer: update on studies of erythropoiesis-stimulating agents.

PMID- 17550054
TI  - Update on neutropenia and myeloid growth factors.

PMID- 17550055
TI  - Mucositis: continuing progress for a continuing need.

PMID- 17550056
TI  - Novel thrombopoietic agents: preliminary activity, potential benefit.

PMID- 17550057
TI  - A time for hope: promising advances in the management of anemia, neutropenia,
      thrombocytopenia, and mucositis.
AB  - The studies highlighted in this issue of The Journal of Supportive Oncology
      provide important and exciting data for the management of anemia, neutropenia,
      thrombocytopenia, and mucositis. Many of these agents are based on an improved
      understanding of the physiologic processes and potential therapeutic targets for
      each of these problems. The challenge for the oncology professional is to
      integrate these findings with considerations of safety, efficacy, cost,
      convenience, established guidelines, and the individual needs of the patient.
      Toxicities remain an important issue in cancer treatment, and nurses play a vital
      role in helping patients prevent, treat, and live with therapy-associated adverse
      events. Integrating recent advances in supportive-care strategies is as important
      to a favorable outcome as selecting the best available active therapy.

PMID- 17550058
TI  - Implementation of cytokines to optimize cancer treatment outcomes.

PMID- 17550059
TI  - AIDS in the Third World: how to stop the HIV infection?
AB  - Of the 38.6 million people living with HIV/AIDS globally, almost 25 million (65%)
      live in sub-Saharan Africa. Preventive strategies and measures fall short, often
      simply because they are not available or are largely male-controlled. A
      preventive HIV vaccine is still far away; hence the drive to develop alternative
      prevention technologies, such as microbicides and oral pre-exposure prophylaxis,
      that could be female controlled. There are, at present, twenty-two anti-HIV drugs
      which have been formally licensed for clinical use in the treatment of HIV
      infections (AIDS): zidovudine, didanosine, zalcitabine, stavudine, lamivudine,
      abacavir, emtricitabine, tenofovir, nevirapine, delavirdine, efavirenz,
      saquinavir, ritonavir, indinavir, nelfinavir, amprenavir, lopinavir, atazanavir,
      fosamprenavir, tipranavir, darunavir and enfuvirtide. These compounds, in
      combination, form the basis of HAART (highly active antiretroviral therapy),
      which has led to the development of a single daily pill existing of the
      combination of tenofovir disoproxil fumarate, emtricitabine and efavirenz, which
      has to be taken orally once daily for the treatment of AIDS. Beyond development
      of new drugs and clinical evaluation of existing medications, several companies
      within the pharmaceutical industry have established innovative policies that
      provide HIV medications at affordable prices in the least-developed countries.
      Reduced pricing is not alone a solution, and thus companies are actively working
      in partnership with the World Health Organization and other multinational groups
      to address roadblocks such as complex registration and procurement systems. Even
      in this period of successful anti-HIV therapy via HAART, a growing number of
      patients is cycling through the various remaining therapeutic options and are
      increasingly becoming dependent of the availability of newly developed anti-HIV
      agents. It is of concern that existing and future therapies will have to be
      effective against newly evolving (including drug-resistant) HIV variants in
      patients who currently face many years, if not decades, of chronic anti-HIV drug
      treatment. In spite of continuous long-term interventions to promote safer sexual
      behaviour, HIV prevalence is high and still rising in many parts of the world.
      The face of the epidemic is now black, female, young and poor..., and female
      controlled methods are urgently needed. Female controlled methods such as
      microbicides and cervical barrier methods provide hopeful perspectives when
      condom use is low due to social, cultural and/or economic factors, but, after
      all, the oral administration of a single daily pill would seem the most
      convenient way to prevent HIV infection, as its protective activity may be
      independent of the route of viral transmission.

PMID- 17550061
TI  - [Building bridges].

PMID- 17550062
TI  - [Infusion therapy safety--combining theory and practice].

PMID- 17550060
TI  - Anti-HIV drugs.
AB  - There are, at present, 22 compounds which have been formally approved (by the US
      Food and Drug Administration) for the treatment of HIV infections (AIDS).
      According to their point of intervention with the HIV replicative cycle, these
      compounds can be classified in 5 categories: (1) NRTIs (nucleoside reverse
      transcriptase inhibitors): azidothymidine, didanosine, zalcitabine, stavudine,
      lamivudine, abacavir and emtricitabine; (2) NtRTIs (nucleotide reverse
      transcriptase inhibitors): tenofovir, administered as its oral prodrug form TDF
      (tenofovir disoproxil fumarate); (3) NNRTIs (non-nucleoside reverse transcriptase
      inhibitors): nevirapine, delavirdine and efavirenz; (4) PIs (HIV protease
      inhibitors): saquinavir, ritonavir, indinavir, nelfinavir, amprenavir, lopinavir,
      atazanavir, fosamprenavir, tipranavir and darunavir; and (5) FIs (fusion
      inhibitors): enfuvirtide. Starting from the drugs which are currently available
      for the treatment of AIDS, numerous combinations could be envisaged. Drug
      combinations are, in principle, aimed at obtaining synergism between the
      compounds (reasonably expected if they act by different mechanisms), while
      reducing the likelihood for drug resistance development. Such anti-HIV drug
      combination regimes were initiated about 10 years ago and have been generally
      referred to as HAART (for highly active antiretroviral therapy). While HAART
      originally consisted of a pill burden of twenty (or more) pills per day, this has
      been gradually diminished over the past few years, and, since July 2006, a all-in
      one pill (Atripla) has become available, which contains three anti-HIV drugs
      (tenofovir disoproxil fumarate, emtricitabine and efavirenz) to be taken as a
      single pill only once daily. Given the information that has been acquired on the
      therapeutic use (efficacy, safety) of tenofovir disoproxil fumarate over the past
      five years, it would now seem mandatory to further consider the prophylactic use
      of TDF [and its combination with emtricitabine (Truvada) and/or Atripla], as a
      single daily pill to prevent HIV infection.

PMID- 17550063
TI  - [Orem theory guided nursing process--protocol of a novel application: assessing
      situational self care needs].

PMID- 17550064
TI  - [Problems in general practice--solutions for general practice: prevention of
      pneumonia].

PMID- 17550065
TI  - [Documenting food intake].

PMID- 17550066
TI  - [Scheduling assistants according to need: future oriented personnel management
      assures success].

PMID- 17550067
TI  - [Documentation using ENP standardized nursing nomenclature: recording detailed
      and current nursing process].

PMID- 17550068
TI  - [Treatment goals of the Ludwigshafen Clinic gGmbH: optimizing and simplifying
      documentation].

PMID- 17550069
TI  - [Introduction to computer assisted documentation in nursing facilities--1:
      Determining the requirements].

PMID- 17550070
TI  - [The effects of DRG introduction on nursing].
AB  - Nursing personnel associate Diagnosis Related Groups (DRG), implemented in German
      hospitals in 2004, mostly with a higher workload and with work that is set apart
      from their patients. Between 2003 and 2005 the Institut fur Pflegewissenschaft,
      Universitat Witten/Herdecke, conducted a longitudinal study to measure changes of
      working structures before, throughout and after the introduction of the case
      based lump sum. At three given dates a structured questionnaire was applied to
      nursing staff and, partially, to doctors in three hospitals in order to assess
      their subjective view on the effects of DRG introduction. RESULTS were compared
      to the actual output by multi-moment-recording. RESULTS: The amount of paperwork
      decreased against expectations. Nevertheless, extra requirements became more
      comprehensive, while the extent of genuine nursing tasks decreased. In 2005 these
      tasks were given a lower amount of time than paperwork and extra requirements.
      Because of methodical restrictions causal relations cannot be established, but
      this trend has to be monitored closely. Further studies have to be carried out to
      examine structural changes of nursing tasks and quality of care.

PMID- 17550071
TI  - [Step by step toward procedural security--1: Clinical pathways need new
      fundamentals].

PMID- 17550072
TI  - [Unusual termination of a career training contract: respecting detours and
      schedules].

PMID- 17550073
TI  - [Human images in nursing--2: Humanism: faith in humanity].

PMID- 17550074
TI  - [From case to case: an "unpopular assignment"].

PMID- 17550075
TI  - [Recognizing and understand disorders: acute confusion as the primary symptom].

PMID- 17550076
TI  - An error about an error.

PMID- 17550077
TI  - It's in the genes.

PMID- 17550078
TI  - Bringing cells to service.

PMID- 17550080
TI  - Egg-stracting answers.

PMID- 17550079
TI  - The power of two.

PMID- 17550081
TI  - Heart maker.

PMID- 17550082
TI  - Code you.

PMID- 17550083
TI  - Operation.

PMID- 17550084
TI  - Genetic tests physicians should know.
AB  - Seven years after completion of the human genome draft sequence, significant
      advances have been made in genetic testing. This article highlights some of the
      newest and most important genetic diagnostic and screening tests to come to
      market in recent years. Application of these tests to clinical practice is also
      discussed.

PMID- 17550085
TI  - A primer on stem cell research.
AB  - Stem cell research holds promise for new treatments for diseases such as
      Parkinson's and injuries such as those to the spinal cord. Yet stem cell research
      remains steeped in controversy. This article defines key terms and outlines some
      of the basic concepts related to stem cell research in order to clarify concepts
      and correct misconceptions. It also briefly discusses what scientists,
      particularly those at the University of Minnesota, are learning about adult and
      embryonic stem cells and their potential for research and treatment.

PMID- 17550086
TI  - [Pediatric health and sickness nursing in Germany].

PMID- 17550087
TI  - [Life between tolerance and allergy].

PMID- 17550088
TI  - [Changes in the personality].

PMID- 17550089
TI  - [Heart valve operation].

PMID- 17550090
TI  - [Picture books: books full of pictures as aides in crisis].

PMID- 17550091
TI  - [Successful completion of the first "Palliative Nursing of Children and
      Adolescents" in Northern Germany].

PMID- 17550092
TI  - [Comment on, "High fluctuation of trainees in ambulatory pediatric nursing" in
      the 2/07, pages 59-61].

PMID- 17550093
TI  - [Current immunization committee includes vaccination against human
      papillomaviruses in the immunization schedule].

PMID- 17550094
TI  - [Responsibilities in general nursing and pediatric nursing are not
      comprehensively regulated by law--guideline regulations do not exist].

PMID- 17550095
TI  - [Poor marks for the speech test].

PMID- 17550096
TI  - Clinical manifestations and vascular events in patients with lupus erythematosus
      anticardiolipin antibodies and raynaud's phenomenon.
AB  - BACKGROUND: Raynaud's phenomenon (RP) and anticardiolipin antibodies (ACL) are
      two common clinical manifestations in patients with systemic lupus erythematosus
      (SLE). RP may lead to digital or limb loss. ACL are associated to thrombotic
      episodes. It is not yet clear if there is an association between RP and the
      presence of ACL in patients with SLE. OBJECTIVES: To study if the presence of
      both RP and ACL in patients with SLE may be associated with certain clinical
      manifestations or thrombotic events compared to SLE patients without RP or ACL.
      METHODS: SLE patients from two lupus clinics were recruited. The patients were
      divided into 4 groups. Patients with RP and positive ACL (RP+ ACL+), patients
      with RP but negative ACL (RP+ ACL-), patients with negative RP and positive ACL
      (RP- ACL+), and patients that were negative for RP and ACL (RP- ACL-) used as the
      control group. Demographic data, diagnostic criteria, clinical manifestations,
      history of arterial thrombosis, venous thrombosis and abortions were recorded. A
      physical examination was done. Anticardiolipin antibodies IgG and IgM were done
      in the rheumatology laboratory at the University of Puerto Rico School of
      Medicine. Descriptive statistics as well as analysis of variances (ANOVA), and
      polytomous logistic regression were used. RESULTS: 236 patients with SLE were
      studied. There was a tendency toward an increase in arterial thrombosis (p-value
      = 0.094) and venous thrombosis (p-value = 0.067) in the group that were positive
      for RP and ACL (RP+ ACL+). Although it was not statistical significant, when
      polytomous logistic regression was used, both arterial and venous thrombosis had
      an increase in relative risk 3.21 for arterial and 3.11 for venous thrombosis.
      Abortions were not increased in any of the four groups. Clinical manifestations
      from SLE did not differ among the four groups. CONCLUSIONS: Patients with both RP
      and ACL seem to be at an increase risk for both arterial and venous thrombotic
      events; these patients may benefit from an antiplatelet medication to prevent
      these events to occur.

PMID- 17550097
TI  - Retinitis pigmentosa in Puerto Rico.
AB  - INTRODUCTION: Previous studies have reported that the prevalence of retinitis
      pigmentosa (RP) varies between one per 3,000 to one in per 5,000 in the general
      population. PURPOSE: To study the incidence and ocular findings of RP in a sub
      urban community in Puerto Rico. METHODS: We conducted a non-concurrent
      prospective study of 10,100 patients in a sub-urban San Juan community. RESULTS:
      44 out of the 10,100 patients had RP (0.44%). Eight out of the 44 patients (18%)
      had nystagmus, twenty-eight (31.8%) had microcornea, 3 patients (6.8%) had
      sluggish papillary reaction. Six patients (13.6%) had mild cataracts, 27
      (65.9%)had attenuated retinal vessels and thirty five patients (81.4%) had bony
      spicules. Fifteen patients (34.1%) out of the 44 had retinitis pigmentosa as part
      of the Bardet-Biedl syndrome. CONCLUSION: Incidence of RP in Puerto Rico is
      higher when compared to Maine and Spain (p < 0.001). Autosomal recessive pattern
      of inheritance is the most common in Puerto Rico. These findings could be due to
      the island's geographic isolation, and inbreeding.

PMID- 17550098
TI  - Comparison of outcomes following combined ECCE-trabeculectomy versus
      phacoemulsification-trabeculectomy.
AB  - PURPOSE: To analyze and compare the main outcomes between trabeculectomies
      combined with extracapsular cataract extraction (ECCE) versus those with
      phacoemulsification (Phaco). PATIENTS AND METHODS: The authors retrospectively
      reviewed one surgeon's 357 consecutive cases (475 eyes) of combined cataract
      extraction, intraocular lens implantation and Mitomycin enhanced trabeculectomy.
      Patients were divided into two groups, those who underwent extracapsular cataract
      extraction (80 eyes) and those having phacoemulsification (395 eyes). Analysis of
      postoperative visual acuity, intraocular pressure (IOP), number of glaucoma
      medications, postoperative adverse events and additional procedures required, was
      done. Minimum follow-up was 12 months with an average of 53 months. RESULTS:
      There was no significant difference (p = 1.000) between the groups in terms of
      visual acuity improvement rate, 66% (ECCE) versus 59% (Phaco). Postoperatively
      IOP with both techniques fell significantly (p < 0.0001). Earlier IOP reduction
      was obtained with Phacoemulsification, but there was no difference by the end of
      the follow up period (14.4 mmHg ECCE vs. 14.1 mmHg Phaco, p = 1.0000).
      Postoperative pressure spikes occurred in 6% versus 10% (p = 0.3995) of the eyes.
      No significant difference (55% ECCE versus 63% Phaco, p = 0.1674) between the two
      groups in terms of glaucoma medication reduction was found. The total number of
      postoperative complications (89% versus 68.5%) were significantly higher (p =
      0.0001) in the ECCE-group, as well as the total number of eyes which required
      further interventions (86% versus 64%, p = 0.0001). CONCLUSION: Both combined
      surgery techniques are effective and yielded similar long-term results. However
      phacoemulsification can decrease the post operative complications associated with
      this surgery.

PMID- 17550099
TI  - Euthanasia, assisted suicide and end-of-life care: attitudes of students,
      residents and attending physicians.
AB  - BACKGROUND: Attitudes in regard to end-of life issues are evolving in Western
      societies. We have sought to trace this evolution in the relatively homogeneous
      cultural setting of Puerto Rico. METHODS: One hundred fifty-two medical students,
      62 medical residents and 84 members of three medical faculties were asked whether
      in terminally ill patients they: 1) would support a request for euthanasia(E); 2)
      if legalized, would engage in, would oppose or would not be opposed to others
      engaging physician-assisted suicide(PAS); 3) would consider ethical to prescribe
      full doses of drugs needed to alleviate pain, even if they knew it would hasten
      death; 4) would agree to limit certain resources for the terminally ill. Gender
      and religious affiliation were also requested. RESULTS: Twenty-eight percent of
      the students, 26% of the residents and 31% of the faculty supported E. Only 13%
      of the students, 18% of the residents and 11% of the faculty would engage in PAS.
      Men were more willing than women to acquiesce to a request for E or PAS.
      Religious affiliation or its absence did not influence the support or opposition
      to E and PAS. If it would hasten death, 86% of the residents, but only 65% of the
      faculty considered ethical to prescribe the dose of drugs needed to alleviate
      pain. More than 2/3 of the students, residents and faculty favored the limiting
      of certain resources for the terminally ill. CONCLUSIONS: In our cultural and
      medical environment, men are more willing than women to engage in E or PAS. The
      attitude towards E and PAS is not influenced by religious affiliation. If it
      hastens death, some still consider unethical to prescribe full doses of drugs
      needed to alleviate pain in the dying patient.

PMID- 17550100
TI  - [Difficulties and concerns identified by Puerto Rican youth with insulin
      dependent diabetes mellitus (IDDM): their relationship with metabolic control,
      hopelessness, social support, and depressive symptoms].
AB  - Insulin-dependent diabetes mellitus (IDDM) is a chronic health condition that
      affects 18 of every 100,000 Puerto Rican youth. Few research studies have been
      performed on the problems that youth with diabetes encounter and how they are
      related to adherence to treatment and adequate metabolic control. Adequate
      metabolic control is associated with fewer short and long-term medical
      complications, as well as better quality of life. Adapting to the demands and
      stressors associated with IDDM and its treatment is a task that can prove to be
      difficult for youth with diabetes due to having to make adjustments, alterations,
      and following a prescribed regimen in their daily activities. The main purpose of
      this investigation was to explore difficulties and worries identified by Puerto
      Rican youth with IDDM. This study examined whether there is a relationship
      between difficulties and worries, and adequate metabolic control, hopelessness,
      social support and depressive symptomatology. One hundred and one youth with IDDM
      between the ages of 8 and 17 (45 male, 56 female) were evaluated. Analysis of
      frequencies, correlations, and comparison tests were performed by group (gender,
      age, diabetes duration, and metabolic control. Results reveal that some of the
      difficulties identified by Puerto Rican youth with IDDM were: not eating candy
      and/or cake, self-monitoring blood glucose at school, doing things on time, and
      waking up early. Among the worries they reported were: insulin reactions and
      thinking that they might have to go to the hospital.

PMID- 17550101
TI  - Exploratory study: breastfeeding knowledge, attitudes towards sexuality and
      breastfeeding, and disposition towards supporting breastfeeding in future Puerto
      Rican male parents.
AB  - Identify the breastfeeding knowledge, the attitudes towards sexuality and
      breastfeeding and the disposition towards supporting breastfeeding in future
      fathers were the aims of this study. A non-probabilistic sample (n = 100) of
      future Puerto Rican male parents was used in this study. A self-administered
      questionnaire was used consisting of four sections. Descriptive statistics were
      used for data analysis and t-test to the inferential analysis. 88.8% of the
      participants presented a low level of knowledge. However, 81.6% had a positive
      attitude toward sexuality and breastfeeding. Also, 92.0% of the participants
      indicated much/enough willingness to support their partners in exclusively
      breastfeeding. Disposition to support the breastfeeding was associated with
      knowledge towards breastfeeding (p = 0.04) and attitudes toward sexuality and
      breastfeeding (p = 0.00). The knowledge and the attitudes, in this study, are
      strongly related with the disposition of the father to supporting the
      breastfeeding in the future.

PMID- 17550102
TI  - Seasonal variation in the incidence of cleft lip and palate based on the age of
      conception.
AB  - BACKGROUND: The purpose of this study is to identify seasonal changes in the
      incidence of Cleft lip and Palate (CL/P) in our population. METHODS: All cases of
      isolated CL/P born in Puerto Rico from January 1998 through December 2002 were
      identified through the Puerto Rican birth defect registry. Conception dates were
      estimated based on the reported last menstrual period. All deliveries during this
      same period were recorded and their conception dates estimated in the same
      manner. The data was separated into 4 groups for each year studied corresponding
      approximately to the four seasons. RESULTS: 484 cases of CL/P were identified
      among 308,968 live births (incidence 1.57/1000 live births. The lowest incidence
      of CL/P was seen during fall and winter (1.24 and 1.38/1000 live births
      respectively) and the highest during spring and summer (1.77 and 1.97/1000 live
      births respectively) (p = 0.002). The seasons with the highest incidence
      correspond to the period when the least number of conceptions are occurring.
      Estimation of relative risks using winter as a reference point (relative risk of
      1.0) showed a decrease in the risk of CL/P in fall to .89 (95th confidence
      interval 0.88 - 1.57), an increase in the risk to 1.28 (CI 1.16 - 2.03) during
      spring and 1.42 (CI 1.16 - 2.03) during summer. CONCLUSIONS: The reported
      seasonal variation in incidence may be secondary to the action of yet to be
      identified teratogens acting on the population at large, or more likely, changes
      in activity and diet patterns of the population.

PMID- 17550103
TI  - [When we "are neither alive nor dead": the Schiavo's case].
AB  - Recently the world was drawn into the news of the Terri Schiavo case. Like in
      that case many other patients and relatives face similar situation. We foresee
      more medical and legal struggles caused primarily by the use of advanced life
      sustaining medical technology that could prolong the life of human beings with
      progressive neurodegenerative disorders, or acquired irreversible brain injury.
      This is an appropriate time to ponder the course of action when we "neither live
      nor die". We agree, as Terri Schiavo's parents' representatives affirm, that
      Terri was not in a terminal state (end-of-life situation). Her life could have
      been prolonged for another fifteen years. However, her clinical presentation was
      not easy to comprehend by some. That way Terri has become a window through which
      the educated public realized that ethical decisions regarding medical affairs are
      always played in an environment of uncertainty and probabilities. One of the
      factors that make such situation more painful is the patient's incompetence to
      respond. In the long run, despite the family tragedy, we can not deny that the
      Schiavo case provides us the basis for a thorough and careful reflection about
      our human brittleness.

PMID- 17550104
TI  - Primary duodenal signet-ring cell carcinoma presenting as gastric outlet
      obstruction.
AB  - Small bowel tumors occur rarely. We present an unusual case of a 68 year old man
      with gastric outlet obstruction secondary to a non-ampullary primary duodenal
      signet ring cell carcinoma. A review of the literature of small bowel malignant
      tumors is presented along with the case.

PMID- 17550105
TI  - Cytomegalovirus polyradiculomyelopathy in AIDS: a case report and review of the
      literature.
AB  - Cytomegalovirus (CMV) neurologic disease is a serious complication of the
      acquired immunodeficiency virus (AIDS). We report the case of a 40 year-old woman
      with AIDS who presented paralysis of lower extremities, areflexia, sensory loss,
      and urinary retention. CMV polymerase chain reaction (PCR) of cerebrospinal fluid
      (CSF) allowed confirmation of CMV polyradiculomyelopathy (PRAM).

PMID- 17550106
TI  - Duodenal duplication with accessory papilla causing recurrent pancreatitis in a
      child: a case report.
AB  - We discuss a 16-year-old male patient who presented with three episodes of
      recurrent pancreatitis within the last 6 months. Preoperative imaging studies
      suggested a choledochal cyst within the second portion of the duodenum. Patient
      was taken to surgery and the lesion was removed. Pathology examination of the
      cyst revealed a duodenal duplication. The accessory pancreatic papilla entering
      the closed duplication cyst was the main cause of the pancreatitis in this child.

PMID- 17550107
TI  - BMI-based stability and performance design for fuzzy-model-based control systems
      subject to parameter uncertainties.
AB  - This paper presents the stability and performance design of a fuzzy-model-based
      control system subject to parameter uncertainties. A nonlinear controller with a
      favorable characteristic to relax the stability conditions is proposed to drive
      the system states of the nonlinear plant to follow those of a stable reference
      model. Stability and performance conditions in terms of bilinear matrix
      inequalities (BMIs) will be derived based on a Lyapunov-based approach. A
      combined genetic algorithm and convex programming technique process will be
      developed to solve the solution to the BMIs. An application example will be given
      to illustrate the merits of the proposed approach.

PMID- 17550108
TI  - Reinforcement learning for resource allocation in LEO satellite networks.
AB  - In this paper, we develop and assess online decision-making algorithms for call
      admission and routing for low Earth orbit (LEO) satellite networks. It has been
      shown in a recent paper that, in a LEO satellite system, a semi-Markov decision
      process formulation of the call admission and routing problem can achieve better
      performance in terms of an average revenue function than existing routing
      methods. However, the conventional dynamic programming (DP) numerical solution
      becomes prohibited as the problem size increases. In this paper, two solution
      methods based on reinforcement learning (RL) are proposed in order to circumvent
      the computational burden of DP. The first method is based on an actor-critic
      method with temporal-difference (TD) learning. The second method is based on a
      critic-only method, called optimistic TD learning. The algorithms enhance
      performance in terms of requirements in storage, computational complexity and
      computational time, and in terms of an overall long-term average revenue function
      that penalizes blocked calls. Numerical studies are carried out, and the results
      obtained show that the RL framework can achieve up to 56% higher average revenue
      over existing routing methods used in LEO satellite networks with reasonable
      storage and computational requirements.

PMID- 17550109
TI  - A recurrent neural network for solving a class of general variational
      inequalities.
AB  - This paper presents a recurrent neural-network model for solving a special class
      of general variational inequalities (GVIs), which includes classical VIs as
      special cases. It is proved that the proposed neural network (NN) for solving
      this class of GVIs can be globally convergent, globally asymptotically stable,
      and globally exponentially stable under different conditions. The proposed NN can
      be viewed as a modified version of the general projection NN existing in the
      literature. Several numerical examples are provided to demonstrate the
      effectiveness and performance of the proposed NN.

PMID- 17550110
TI  - Additive support vector machines for pattern classification.
AB  - Support vector machines (SVMs) are one of the most popular methodologies for the
      design of pattern classification systems with sound theoretical foundations and
      high generalizing performance. The SVM framework focuses on linear and nonlinear
      models that maximize the separating margin between objects belonging in different
      classes. This paper extends the SVM modeling context toward the development of
      additive models that combine the simplicity and transparency/interpretability of
      linear classifiers with the generalizing performance of nonlinear models.
      Experimental results are also presented on the performance of the new methodology
      over existing SVM techniques.

PMID- 17550111
TI  - Relaxed stabilization criteria for discrete-time T-S fuzzy control systems based
      on a switching fuzzy model and piecewise Lyapunov function.
AB  - In this paper, two new relaxed stabilization criteria for discrete-time T-S fuzzy
      systems are proposed. In the beginning, the operation state space is divided into
      several subregions, and then, the T-S fuzzy system is transformed to an
      equivalent switching fuzzy system corresponding to each subregion. Consequently,
      based on the piecewise Lyapunov function, the stabilization criteria of the
      switching fuzzy system are derived. The criteria have two features: 1) the
      behavior of the two successive states of the system is considered in the
      inequalities and 2) the interactions among the fuzzy subsystems in each subregion
      Sj are presented by one matrix Xj. Due to the above two features, the feasible
      solutions of the inequalities in the criteria are much easier to be found. In
      other words, the criteria are much more relaxed than the existing criteria
      proposed in other literature. The proposed conditions in the criteria and the
      fuzzy control design can be solved and achieved by means of linear matrix
      inequality tools. Two examples are given to present the superiority of the
      proposed criteria and the effectiveness of the fuzzy controller's design,
      respectively.

PMID- 17550112
TI  - Multiobjective optimization and hybrid evolutionary algorithm to solve
      constrained optimization problems.
AB  - This paper presents a novel evolutionary algorithm (EA) for constrained
      optimization problems, i.e., the hybrid constrained optimization EA (HCOEA). This
      algorithm effectively combines multiobjective optimization with global and local
      search models. In performing the global search, a niching genetic algorithm based
      on tournament selection is proposed. Also, HCOEA has adopted a parallel local
      search operator that implements a clustering partition of the population and
      multiparent crossover to generate the offspring population. Then, nondominated
      individuals in the offspring population are used to replace the dominated
      individuals in the parent population. Meanwhile, the best infeasible individual
      replacement scheme is devised for the purpose of rapidly guiding the population
      toward the feasible region of the search space. During the evolutionary process,
      the global search model effectively promotes high population diversity, and the
      local search model remarkably accelerates the convergence speed. HCOEA is tested
      on 13 well-known benchmark functions, and the experimental results suggest that
      it is more robust and efficient than other state-of-the-art algorithms from the
      literature in terms of the selected performance metrics, such as the best,
      median, mean, and worst objective function values and the standard deviations.

PMID- 17550113
TI  - A hybrid quantum-inspired genetic algorithm for multiobjective flow shop
      scheduling.
AB  - This paper proposes a hybrid quantum-inspired genetic algorithm (HQGA) for the
      multiobjective flow shop scheduling problem (FSSP), which is a typical NP-hard
      combinatorial optimization problem with strong engineering backgrounds. On the
      one hand, a quantum-inspired GA (QGA) based on Q-bit representation is applied
      for exploration in the discrete 0-1 hyperspace by using the updating operator of
      quantum gate and genetic operators of Q-bit. Moreover, random-key representation
      is used to convert the Q-bit representation to job permutation for evaluating the
      objective values of the schedule solution. On the other hand, permutation-based
      GA (PGA) is applied for both performing exploration in permutation-based
      scheduling space and stressing exploitation for good schedule solutions. To
      evaluate solutions in multiobjective sense, a randomly weighted linear-sum
      function is used in QGA, and a nondominated sorting technique including
      classification of Pareto fronts and fitness assignment is applied in PGA with
      regard to both proximity and diversity of solutions. To maintain the diversity of
      the population, two trimming techniques for population are proposed. The proposed
      HQGA is tested based on some multiobjective FSSPs. Simulation results and
      comparisons based on several performance metrics demonstrate the effectiveness of
      the proposed HQGA.

PMID- 17550114
TI  - Adaptation and change detection with a sequential Monte Carlo scheme.
AB  - Given the sequential data from an unknown target system with changing parameters,
      the first part of this paper discusses online algorithms that adapt to smooth as
      well as abrupt changes. This paper examines four different parameter/
      hyperparameter dynamics for online learning and compares their performance within
      an online Bayesian learning framework. Using the dynamics that performed best in
      the first part, the second part of this paper attempts to perform change
      detection in unknown systems in terms of the time dependence of the marginal
      likelihood. Because of the sequential nature of the algorithms, a sequential
      Monte Carlo scheme (particle filter) is a natural means for implementation.

PMID- 17550115
TI  - Adaptive robust motion/force control of holonomic-constrained nonholonomic mobile
      manipulators.
AB  - In this paper, adaptive robust force/motion control strategies are presented for
      mobile manipulators under both holonomic and nonholonomic constraints in the
      presence of uncertainties and disturbances. The proposed control is robust not
      only to parameter uncertainties such as mass variations but also to external ones
      such as disturbances. The stability of the closed-loop system and the boundedness
      of tracking errors are proved using Lyapunov stability synthesis. The proposed
      control strategies guarantee that the system motion converges to the desired
      manifold with prescribed performance and the bounded constraint force. Simulation
      results validate that the motion of the system converges to the desired
      trajectory, and the constraint force converges to the desired force.

PMID- 17550116
TI  - Sampled-data fuzzy controller for time-delay nonlinear systems: fuzzy-model-based
      LMI approach.
AB  - This paper presents the stability analysis and performance design for a sampled
      data fuzzy control system with time delay, which is formed by a nonlinear plant
      with time delay and a sampled-data fuzzy controller connected in a closed loop.
      As the sampled-data fuzzy controller can be implemented by a microcontroller or a
      digital computer, the implementation time and cost can be reduced. However, the
      sampling activity and time delay, which are potential causes of system
      instability, will complicate the system dynamics and make the stability analysis
      much more difficult than that for a pure continuous-time fuzzy control system. In
      this paper, a sampled-data fuzzy controller with enhanced nonlinearity
      compensation ability is proposed. Based on the fuzzy-model-based control
      approach, linear matrix inequality (LMI)-based stability conditions are derived
      to guarantee the system stability. By using a descriptor representation, the
      complexity of the sampled-data fuzzy control system with time delay can be
      reduced to ease the stability analysis, which effectively leads to a smaller
      number of LMI-stability conditions. Information of the membership functions of
      both the fuzzy plant model and fuzzy controller are considered, which allows
      arbitrary matrices to be introduced, to ease the satisfaction of the stability
      conditions. An application example will be given to show the merits and design
      procedure of the proposed approach. Furthermore, LMI-based performance conditions
      are derived to aid the design of a well-performed sampled-data fuzzy controller.

PMID- 17550117
TI  - Fuzzy weighted support vector regression with a fuzzy partition.
AB  - The problem of the traditional support vector regression (SVR) approach, referred
      to as the global SVR approach, is the incapability of interpreting local behavior
      of the estimated models. An approach called the local SVR approach was proposed
      in the literature to cope with this problem. Although the local SVR approach can
      indeed model local behavior of models better than the global SVR approach does,
      the local SVR approach still has the problem of boundary effects, which may
      generate a large bias at the boundary and also need more time to calculate. In
      this paper, the fuzzy weighted SVR with a fuzzy partition is proposed. Because
      the concept of locally weighted regression is not used in the proposed approach,
      the boundary effects will not appear. The proposed method first employs the fuzzy
      c-mean clustering algorithm to split training data into several training subsets.
      Then, the local-regression models (LRMs) are independently obtained by the SVR
      approach for each training subset. Finally, those LRMs are combined by a fuzzy
      weighted mechanism to form the output. Experimental results show that the
      proposed approach needs less computational time than the local SVR approach and
      can have more accurate results than the local/global SVR approaches does.

PMID- 17550118
TI  - Spatio-temporal feature-extraction techniques for isolated gesture recognition in
      Arabic sign language.
AB  - This paper presents various spatio-temporal feature-extraction techniques with
      applications to online and offline recognitions of isolated Arabic Sign Language
      gestures. The temporal features of a video-based gesture are extracted through
      forward, backward, and bidirectional predictions. The prediction errors are
      thresholded and accumulated into one image that represents the motion of the
      sequence. The motion representation is then followed by spatial-domain feature
      extractions. As such, the temporal dependencies are eliminated and the whole
      video sequence is represented by a few coefficients. The linear separability of
      the extracted features is assessed, and its suitability for both parametric and
      nonparametric classification techniques is elaborated upon. The proposed feature
      extraction scheme was complemented by simple classification techniques, namely, K
      nearest neighbor (KNN) and Bayesian, i.e., likelihood ratio, classifiers.
      Experimental results showed classification performance ranging from 97% to 100%
      recognition rates. To validate our proposed technique, we have conducted a series
      of experiments using the classical way of classifying data with temporal
      dependencies, namely, hidden Markov models (HMMs). Experimental results revealed
      that the proposed feature-extraction scheme combined with simple KNN or Bayesian
      classification yields comparable results to the classical HMM-based scheme.
      Moreover, since the proposed scheme compresses the motion information of an image
      sequence into a single image, it allows for using simple classification
      techniques where the temporal dimension is eliminated. This is actually
      advantageous for both computational and storage requirements of the classifier.

PMID- 17550119
TI  - RCMAC-based adaptive control for uncertain nonlinear systems.
AB  - An adaptive control system, using a recurrent cerebellar model articulation
      controller (RCMAC) and based on a sliding mode technique, is developed for
      uncertain nonlinear systems. The proposed dynamic structure of RCMAC has superior
      capability to the conventional static cerebellar model articulation controller in
      an efficient learning mechanism and dynamic response. Temporal relations are
      embedded in RCMAC by adding feedback connections in the association memory space
      so that the RCMAC provides a dynamical structure. The proposed control system
      consists of an adaptive RCMAC and a compensated controller. The adaptive RCMAC is
      used to mimic an ideal sliding mode controller, and the compensated controller is
      designed to compensate for the approximation error between the ideal sliding mode
      controller and the adaptive RCMAC. The online adaptive laws of the control system
      are derived based on the Lyapunov stability theorem, so that the stability of the
      system can be guaranteed. In addition, in order to relax the requirement of the
      approximation error bound, an estimation law is derived to estimate the error
      bound. Finally, the simulation and experimental studies demonstrate the
      effectiveness of the proposed control scheme for the nonlinear systems with
      unknown dynamic functions.

PMID- 17550120
TI  - Interpretation of spatial language in a map navigation task.
AB  - We have developed components of an automated system that understands and follows
      navigational instructions. The system has prior knowledge of the geometry and
      landmarks of specific maps. This knowledge is exploited to infer complex paths
      through maps based on natural language descriptions. The approach is based on an
      analysis of verbal commands in terms of elementary semantic units that are
      composed to generate a probability distribution over possible spatial paths in a
      map. An integration mechanism based on dynamic programming guides this language
      to-path translation process, ensuring that resulting paths satisfy continuity and
      smoothness criteria. In the current implementation, parsing of text into semantic
      units is performed manually. Composition and interpretation of semantic units
      into spatial paths is performed automatically. In the evaluations, we show that
      the system accurately predicts the speakers' intended meanings for a range of
      instructions. This paper provides building blocks for a complete system that,
      when combined with robust parsing technologies, could lead to a fully automatic
      spatial language interpretation system.

PMID- 17550121
TI  - Patch models and their applications to multivehicle command and control.
AB  - We introduce patch models, a computational modeling formalism for multivehicle
      combat domains, based on spatiotemporal abstraction methods developed in the
      computer science community. The framework yields models that are expressive
      enough to accommodate nontrivial controlled vehicle dynamics while being within
      the representational capabilities of common artificial intelligence techniques
      used in the construction of autonomous systems. The framework allows several key
      design requirements of next-generation network-centric command and control
      systems, such as maintenance of shared situation awareness, to be achieved. Major
      features include support for multiple situation models at each decision node and
      rapid mission plan adaptation. We describe the formal specification of patch
      models and our prototype implementation, i.e., Patchworks. The capabilities of
      patch models are validated through a combat mission simulation in Patchworks,
      which involves two defending teams protecting a camp from an enemy attacking
      team.

PMID- 17550122
TI  - Desynchronizing a chaotic pattern recognition neural network to model inaccurate
      perception.
AB  - The usual goal of modeling natural and artificial perception involves determining
      how a system can extract the object that it perceives from an image that is
      noisy. The "inverse" of this problem is one of modeling how even a clear image
      can be perceived to be blurred in certain contexts. To our knowledge, there is no
      solution to this in the literature other than for an oversimplified model in
      which the true image is garbled with noise by the perceiver himself. In this
      paper, we propose a chaotic model of pattern recognition (PR) for the theory of
      "blurring." This paper, which is an extension to a companion paper demonstrates
      how one can model blurring from the view point of a chaotic PR system. Unlike the
      companion paper in which a chaotic PR system extracts the pattern from the input,
      in this case, we show that even without the inclusion of additional noise,
      perception of an object can be "blurred" if the dynamics of the chaotic system
      are modified. We thus propose a formal model and present an analysis using the
      Lyapunov exponents and the Routh-Hurwitz criterion. We also demonstrate
      experimentally the validity of our model by using a numeral data set. A byproduct
      of this model is the theoretical possibility of desynchronization of the periodic
      behavior of the brain (as a chaotic system), rendering us the possibility of
      predicting, controlling, and annulling epileptic behavior.

PMID- 17550123
TI  - A mathematical programming method for formulating a fuzzy regression model based
      on distance criterion.
AB  - Fuzzy regression models are useful to investigate the relationship between
      explanatory and response variables with fuzzy observations. Different from
      previous studies, this correspondence proposes a mathematical programming method
      to construct a fuzzy regression model based on a distance criterion. The
      objective of the mathematical programming is to minimize the sum of distances
      between the estimated and observed responses on the X axis, such that the fuzzy
      regression model constructed has the minimal total estimation error in distance.
      Only several alpha-cuts of fuzzy observations are needed as inputs to the
      mathematical programming model; therefore, the applications are not restricted to
      triangular fuzzy numbers. Three examples, adopted in the previous studies, and a
      larger example, modified from the crisp case, are used to illustrate the
      performance of the proposed approach. The results indicate that the proposed
      model has better performance than those in the previous studies based on either
      distance criterion or Kim and Bishu's criterion. In addition, the efficiency and
      effectiveness for solving the larger example by the proposed model are also
      satisfactory.

PMID- 17550124
TI  - Stochastic exponential stability for Markovian jumping BAM neural networks with
      time-varying delays.
AB  - This correspondence provides stochastic exponential stability for Markovian
      jumping bidirectional associative memory neural networks with time-varying
      delays. An approach combining the Lyapunov functional with linear matrix
      inequality is taken to study the problems. Some criteria for the stochastic
      exponential stability are derived. The results obtained in this correspondence
      are less conservative, less restrictive, and more computationally efficient than
      the ones reported so far in the literature.

PMID- 17550125
TI  - Stability analysis of Takagi-Sugeno fuzzy cellular neural networks with time
      varying delays.
AB  - This correspondence investigates the global exponential stability problem of
      Takagi-Sugeno fuzzy cellular neural networks with time-varying delays (TSFDCNNs).
      Based on the Lyapunov-Krasovskii functional theory and linear matrix inequality
      technique, a less conservative delay-dependent stability criterion is derived to
      guarantee the exponential stability of TSFDCNNs. By constructing a Lyapunov
      Krasovskii functional, the supplementary requirement that the time derivative of
      time-varying delays must be smaller than one is released in the proposed delay
      dependent stability criterion. Two illustrative examples are provided to verify
      the effectiveness of the proposed results.

PMID- 17550126
TI  - Relaxed stability and performance conditions for Takagi-Sugeno fuzzy systems with
      knowledge on membership function overlap.
AB  - This correspondence presents a relaxation of some earlier linear matrix
      inequality (LMI) conditions, which allow setting up less conservative stability
      or performance conditions for Takagi-Sugeno fuzzy models. Unlike the previous
      literature, this correspondence takes into account the knowledge of the
      membership functions' shape by considering bounds on them and their cross
      products (interpreted as an overlap measure), introducing auxiliary LMI
      variables. Numerical examples illustrate the achieved improvements.

PMID- 17550127
TI  - Impulsive effects on stability of fuzzy Cohen-Grossberg neural networks with time
      varying delays.
AB  - In this correspondence, the impulsive effects on the stability of fuzzy Cohen
      Grossberg neural networks (FCGNNs) with time-varying delays are considered.
      Several sufficient conditions are obtained ensuring global exponential stability
      of equilibrium point for the neural networks by the idea of vector Lyapunov
      function, M-matrix theory, and analytic methods. Moreover, the estimation for
      exponential convergence rate index is proposed. The obtained results not only
      show that the stability still remains under certain impulsive perturbations for
      the continuous stable FCGNNs with time-varying delays, but also present an
      approach to stabilize the unstable FCGNNs with time-varying delays by utilizing
      impulsive effects. An example with simulations is given to show the effectiveness
      of the obtained results.

PMID- 17550128
TI  - Dynamic range-based distance measure for microarray expressions and a fast gene
      ordering algorithm.
AB  - This investigation deals with a new distance measure for genes using their
      microarray expressions and a new algorithm for fast gene ordering without
      clustering. This distance measure is called "Maxrange distance," where the
      distance between two genes corresponding to a particular type of experiment is
      computed using a normalization factor, which is dependent on the dynamic range of
      the gene expression values of that experiment. The new gene-ordering method
      called "Minimal Neighbor" is based on the concept of nearest neighbor heuristic
      involving O(n2) time complexity. The superiority of this distance measure and the
      comparability of the ordering algorithm have been extensively established on
      widely studied microarray data sets by performing statistical tests. An
      interesting application of this ordering algorithm is also demonstrated for
      finding useful groups of genes within clusters obtained from a nonhierarchical
      clustering method like the self-organizing map.

PMID- 17550129
TI  - Neurotrophin receptors and heparanase: a functional axis in human medulloblastoma
      invasion.
AB  - Medulloblastoma (MB) is the most common malignant brain tumor of childhood.
      Although modern therapy has produced five-year survival rates as high as 70% for
      some MB patients, this resulted in significant long-term treatment-related
      morbidity. The cellular mechanisms involved in metastatic spread of
      medulloblastoma are largely unknown. Neurotrophins (NT) comprise a family of
      structurally and functionally related neurotrophic factors that are critical for
      central nervous system (CNS) development with nerve growth factor (NGF) being the
      prototypic NT. NT acts through two groups of structurally unrelated neurotrophin
      receptors (NTR): a family of receptor tyrosine kinases (Trks, mainly TrkA, TrkB,
      and TrkC) and a tumor necrosis factor receptor (TNFR)-like molecule called p75NTR
      TrkC expression is a good prognostic indicator for MB. TrkC binds only to
      neurotrophin-3 (NT-3) whereas p75 binds to all NT family members. Importantly,
      little is known about the biological functions of p75 in primitive
      neuroectodermal tumors such as MB. In contrast, NT-regulated heparanase (HPSE) is
      a unique extracellular matrix-degrading enzyme known to be associated with tumor
      progression in a wide variety of cancers. However, HPSE roles in MB invasive
      pathways have not been investigated. We provide evidence of a differential
      expression of HPSE in newly-developed medulloblastoma cell lines. Secondly, we
      show a correlation between HPSE expression and the invasive properties of these
      medulloblastoma lines. Thirdly, by performing investigations to elucidate
      prognostic implications of HPSE and TrkC/p75NTR expression in MB, we demonstrate
      a correlation between p75NTR and HPSE expression. Finally, by using antibodies
      specific to TrkC and immunohistochemistry (IHC) we prove that IHC scores reveal a
      significant expression of HPSE in 76% of MB tissues from children aged 3 years
      and older. Taken together, our data provide evidence that HPSE functionality, in
      a context linked to TrkC and p75NTR activation, may play critical roles in
      medulloblastoma tumor invasion and progression.

PMID- 17550130
TI  - Molecular genetics of prostate cancer: clinical translational opportunities.
AB  - Prostate cancer (PC) development reflects a complex sequence of biologic and
      molecular events. Several inheritable and somatic genetic changes have been
      identified. The knowledge of the molecular basis of PC can improve our
      understanding of the causes of this common cancer and provide information on
      prognosis and treatment. To date, however, no molecular studies have yet yielded
      consistent information that is ready to be incorporated into clinical practice.
      We reviewed the current literature on the molecular biology of prostate cancer
      and analyzed different potential tumor markers according to the classical
      concepts of oncogenes, suppressor genes, and the more modern concepts of genes
      involved in detoxification or inflammatory pathways of cancer progression. This
      review aims to identify trends in PC research and suggests potential clinical
      applications for diagnosis, prognosis, prevention and treatment.

PMID- 17550131
TI  - Cellular redox status regulates hypoxia inducible factor-1 activity. Role in
      tumour development.
AB  - The transcription factor hypoxia-inducible factor-1 (HIF-1) regulates the
      expression of more than 100 genes involved in cellular adaptation and survival
      under hypoxic stress. Activation of HIF-1 is associated with numerous
      physiological and pathological processes that include tumorigenesis, vascular
      remodelling, inflammation, and hypoxia/ischemia-related tissue damage.
      Experimental data support the concept that modulation of Reactive Oxygen Species
      (ROS) levels have an important impact on the hypoxic response mediated by HIF-1
      alpha. However, ROS generation, the exact kinetics and conditions of ROS
      production and their specific relevance to HIF-l alpha activation are issue still
      to be clarified. Clinical studies suggested that HIF-1 activation correlates
      directly with advanced disease stages and treatment resistance among cancer
      patients. Preclinical studies support the inhibition of HIF-1 as a major
      molecular target for anti-tumour drug discovery. Considerable effort is underway
      to identify therapeutically useful molecule HIF-1 inhibitors. Most of the
      compounds discovered to inhibit HIF-1 are natural products or synthetic compounds
      with structures that are based on natural product leads. Natural products have
      also served a vital role as molecular probes to elucidate the pathways that
      regulate HIF-1 activity. Many of the substances found to inhibit HIF-I are non
      druggable compounds that are too cytotoxic to serve as drug leads. The
      application of high-throughput screening methods, complementary molecular
      targeted assays, and structurally diverse chemical libraries hold promise for the
      discovery of therapeutically useful HIF-1 inhibitors.

PMID- 17550132
TI  - Continuous infusion of 5-fluorouracil with versus without low-dose, consecutive
      administration of cisplatin in advanced colorectal cancer. A prospective
      randomized phase II study.
AB  - Recently, the treatment of advanced gastric cancer by continuous infusion of 5
      fluorouracil (5-FU) with low-dose cisplatin (CDDP) has improved efficacy without
      severe toxicities. The possible effectiveness of 5-FU+low-dose CDDP for
      colorectal cancer (CRC) is intriguing. One hundred fifty-five patients with far
      advanced CRC including at least one measurable lesion were enrolled in a
      prospective randomized clinical trial funded by the Japanese Foundation for
      Multidisciplinary Treatment of Cancer. These patients were assigned to the two
      arms to assess the value of low-dose CDDP when added to a continuous intravenous
      infusion of 5-FU at a dose of 300 mg/m(2)/24 hrs in a one-week cycle consisting
      of 5 days of treatment and 2 days of rest for at least 12 weeks. CD-DP was given
      intravenously at a dose of 3 mg/m(2) on days 1-5 and days 8-12, and then at a
      dose of 7 mg/m(2) twice a week. Three patients were excluded from the trial. The
      response rate in the 5-FU+low-dose CDDP arm (n=75) was significantly higher than
      that in the 5-FU arm (n=77) (25.3% vs. 11.7%; P = 0.037). There was no
      significant difference in the median overall survival time between the 5-FU+low
      dose CDDP arm and the 5-FU arm (479 and 491 days, respectively). Grades 3/4
      toxicities occurred infrequently in both arms. The quality of life was almost the
      same between the arms. Low-dose CDDP improved the response rate while keeping
      toxicities within clinically acceptable limits. However, this combined treatment
      did not confer a survival advantage over treatment with continuous infusion of 5
      FU alone for patients with far-advanced CRC; that might be attributable to the
      short CDDP administration setting of 12 weeks.

PMID- 17550133
TI  - Phase II study of preoperative irradiation and chemotherapy with capecitabine in
      patients with locally advanced rectal carcinoma.
AB  - Preoperative chemoradiotherapy has demonstrated to improve resectability and
      local control in locally advanced rectal cancer (LARC). 5-fluorouracil (5FU) has
      traditionally been the drug of choice in combination with radiation therapy.
      Early studies of capecitabine (CAP) have shown its potential to replace 5FU.
      Between March 2002 and April 2005, 31 patients with newly diagnosed LARC (T2 N+ 2
      cases, T3 N0-N+ 25 cases, T4 N0-N+ 4 cases) received the combined treatment.
      Surgery was planned 6-8 weeks after chemoradiation. Adjuvant chemotherapy with
      5FU plus leucovorin for 6 courses was given in pN+ patients. All patients
      completed the planned treatment. Grade 3 acute toxicity was observed in 5
      patients (16%). Nineteen patients (61%) had a downstaging. A complete
      pathological remission was observed in 3 cases (10%). Median follow-up is of 23
      months (range; 6-36 months). The results of this experience confirm the data of
      the literature about the feasibility and efficacy of a neoadjuvant treatment with
      radiation and CAP in LARC.

PMID- 17550134
TI  - Sentinel node biopsy in cutaneous melanoma: correlations between melanoma
      prognostic factors and sentinel node status.
AB  - This study aims to correlate the most important prognostic factors of primary
      melanoma with sentinel node (SN) positive for metastases. We have enrolled 84
      patients subjected to sentinel node biopsies for cutaneous melanomas of Breslow's
      thickness > or = 0.75 mm by using an intra-operative gamma probe after
      lymphoscintigraphy, without blue dye support. SN metastases were reported in 27%
      of cases (14% by histology and 13% by immunohistochemistry). By chi-square test
      Breslow's thickness > 2mm (p= 0.004), IV and V Clark's level (p= 0.02),
      ulceration (p= 0.05) and high mitotic rate (p= 0.05) were statistically
      significant (p < 0.05) with reference to SN positive for metastases, unlike the
      site of cutaneous melanoma, vertical growth phase, tumour infiltrating
      lymphocytes, regression and vascular invasion. Breslow's thickness remains the
      first prognostic factor to be considered for sentinel node biopsy in cutaneous
      melanoma, but other markers must be carefully estimated.

PMID- 17550136
TI  - Antitumor resistance formation in animals in early neonatal period.
AB  - Immunization of new-born mice during the first three days after birth enhances
      immunity in adult life, and it remains high throughout the entire life course.
      The antitumor resistance is raised so high in order to produce cancerogenesis
      blockade caused by 20-methylcholanthrene injection to adult animals even one year
      after vaccination. The dynamics of growth of new-borns shows that immediately
      after birth the animal growth proceeds very quickly, following an exponential
      law. The same occurs in rats and even in human beings. Vaccination of animals
      during fast growth phase ensures an antitumor effect, while vaccination after
      fast growth phase leads to antitumor immunity breakdown. It was assumed fetal
      lymphocytes do not attain full sexual maturity and their cytotoxic properties
      start developing only after birth. This hypothesis is in full agreement with our
      results. Vaccination of new-borns during fast growth phase leads to a significant
      increase of immature lymphocytes of those clones which are sensitive to an
      injected antigen. Upon vaccination termination, these lymphocytes attain complete
      maturation and remain in tissues, thereby ensuring a prolonged and high immunity.
      Our earlier experiments clearly demonstrated the increase in lymphocytes number
      in animals which had been exposed to early postnatal immunization. The kinetic
      analysis showed that full tumor destruction would be only possible if the rate of
      tumor cells destruction by cytotoxic lymphocytes is greater than the rate of
      tumor cells reproduction, as the tumor is incapable to make up for loss of its
      own cells. Immunization during fast growth phase does allow maximum increase in
      the number of cytotoxic lymphocytes and, thereby, enhance an entire cell immunity
      - unattainable after full lymphocyte maturation.

PMID- 17550135
TI  - Patients with malignant or pre-malignant cervical lesion have increased risk of
      becoming hepatitis B carrier.
AB  - Human Papillomavirus (HPV) and Hepatitis B virus (HBV) are known aetiology of
      cervical and hepatocellular carcinoma, respectively. Both diseases share a
      similar clinical course, that is, the vast majority of those infected by these
      two viruses can eradicate the viruses spontaneously. A small sub-group who fails
      to clear the virus becomes chronic carrier and can progress to carcinoma many
      years later. We postulated that patients with pre-malignant or malignant cervical
      lesion are at increased risk of becoming chronic HBV carrier if infected, which
      may be attributed to inherent immunological deficiency against viral infection.
      We tested HBV carrier status from 288 patients with cervical carcinoma, 242
      patients with high grade cervical intra-epithelial neoplasia (CIN) and 311 women
      with neither of the above conditions as control subjects. The HBV carrier rate in
      the Cancer Group, CIN Group and Control Group was 21.4%, 24.1% and 10.6%. The
      carrier rate was significantly higher in both the Cancer Group (p<0.01) and the
      CIN Group (p<0.01), compared to the Control Group. Our study suggests that a
      common immunological mechanism is involved in eradication of HBV and HPV
      infections and inherent immuno-deficiency might lead to an association of HBV
      carrier status with cervical carcinoma. Further studies are needed to confirm our
      findings and delineate the mechanism involved.

PMID- 17550137
TI  - Synergic CSE1L/CAS, TNFR-1, and p53 apoptotic pathways in combined interferon
      gamma/adriamycin-induced apoptosis of Hep G2 hepatoma cells.
AB  - Many cancers are chemotherapy-resistant. Chemotherapy combined with immunotherapy
      offers a potential avenue for the treatment of chemotherapy-resistant cancers. In
      this study, we investigated the apoptotic pathways induced by combined interferon
      gamma/adriamycin treatment in Hep G2 cells. Our data showed that Hep G2 cells
      treated with combined interferon-gamma/adriamycin enhanced cell apoptosis in
      comparison with that of cells treated with adriamycin. Interferon-y increased
      TNFR-1, CSE1L/CAS (cellular apoptosis susceptibility protein), Bax, and Bad
      levels. Adriamycin increased p53 and Bax, but not TNFR- 1 and CAS levels.
      Interferon-y did not increase p53 accumulation; nevertheless it enhanced
      adriamycin-induced p53 accumulation. Overexpression of IRF-1 augmented the
      combined interferon-gamma/adriamycin-induced p53 accumulation. Interferon-gamma
      co-treatment increased the stability of p53 protein induced by adriamycin. Our
      data suggest that TNF-gamma may greatly enhance the combined interferon
      gamma/chemotherapeutic drug-induced apoptosis of cancers. Our findings also
      indicate that CAS, TN-FR-1, p53, Bax, and Bad may be the targets for the
      interferon-y-based chemo-immunotherapy of the chemotherapy-resistant cancers.

PMID- 17550138
TI  - Genetic analysis of high-metastatic clone of RCT sarcoma in mice, and its growth
      regression in vivo in response to angiogenesis inhibitor TNP-470.
AB  - Genetic analysis of a high-metastatic clone of RCT sarcoma (HM-RCT) was the aim
      of the study. HM-RCT was developed by the lung passage as well as limiting
      dilution method from the original RCT sarcoma, in which a tumor was spontaneously
      developed in a C3H/He mouse. HM-RCT expressed enhanced POU domain (class 2,
      associating factor 1), adenylate cyclase 7, procollagen type III (alpha), A
      kinase anchor protein 4 and Ehm (expressed on high-metastatic cells) and 11
      expressed sequence tags (ESTs). compared with the original clone of RCT. Eighteen
      specific genes and 14 ESTs were underexpressed in HM-RCT. We investigated the
      effects of angiogenesis inhibitor TNP-470 on tumor growth and metastasis of this
      HM-RCT in vivo. In an experimental group, mice received TNP-470 (30 mg/kg)
      intraperitoneally every other day. After 5 weeks, the growth of the TNP-470
      treated tumor was significantly suppressed in vivo, but did not affect the
      metastasis. The proportion of positive PCNA-stained cells and cellular telomerase
      activity was significantly low in response to TNP-470.

PMID- 17550139
TI  - Ki-67 expression in melanoma. A potential method of risk assessment for the
      patient with a positive sentinel node.
AB  - Melanoma patients with a positive sentinel node biopsy generally proceed to
      regional lymph node dissection, though ultimately only around 20% have evidence
      of tumour in their "non-sentinel" nodes. A means to identify patients at high
      risk of non-sentinel node involvement could potentially spare a large number of
      patients a procedure with significant morbidity. The proliferation marker Ki-67
      has been associated with tumour progression in primary melanoma but has not been
      extensively studied in metastases. The study aims to investigate Ki-67 in primary
      melanoma and lymph node metastases and investigate any relationship with disease
      progression. Tissue Arrays of primary melanoma (n=79) and lymph node metastases
      (n=92) were constructed from paraffin embedded tissue and Ki-67 expression
      examined by immunohistochemistry. Staining positivity and intensity were assessed
      and correlated with standard staging criteria and clinical outcome. High Ki-67
      expression was associated with both Breslow thickness (chi(2)=8.54, p=0.035) and
      presence of ulceration (Fisher's Exact test p=0.003) in primary melanoma. In
      lymph node metastases high Ki-67 expression correlated with Nodal (N) Stage
      (chi(2)=8.193, p=0.0 17). High Ki-67 expression is associated with melanoma
      progression and multiple lymph node involvement. This might potentially form the
      basis of a risk analysis for patients with positive sentinel nodes.

PMID- 17550140
TI  - Loss of expression of Kruppel-like factor 6 in primary hepatocellular carcinoma
      and hepatoma cell lines.
AB  - KLF6 (Zf9, COPEB), an ubiquitous transcription factor, maps to chromosome 10p.
      Recently, KLF6 was found to have a more generalized role in tumorigenesis as a
      candidate tumor suppressor gene for some tumors. However, results from other
      published studies seem not to be in agreement with data from previous studies.
      Gene-expression analysis is increasingly important in biological research. Loss
      of expression is one of the mechanisms to functionally inactivate a tumor
      suppressor gene. To investigate the expression change of KLF6 gene associated
      with HCC as a step toward a better understanding of the molecular
      pathophysiology, and to provide the basis for analysis of KLF6 gene in HCC
      carcinogenesis. We analyzed the expression of KLF6 mRNA in 26 samples of HCC
      tissues and hepatoma cell lines(Hep3B and HepG2) detected by Real-Time
      quantitative RT-PCR (qRT-PCR) and conventional RT-PCR assay. To confirm and
      extend the data obtained at RNA level, we performed detailed immunoblotting
      analysis on HCC tissues and hepatoma cell lines using a rabbit polyclonal
      antibody specific for KLF6. NKLF6 detected by qRT-PCR from HCC and corresponding
      noncancerous tissues was 0.04+/-0.038 and 0.116+/-0.101, respectively. These data
      demonstrated that KLF6 mRNA level was significantly decreased in HCC, compared
      with corresponding noncancerous tissues (t =3.683 , P<0.001). The frequency of
      Hepatoma Cell Lines with KLF6 down-regulation detected by conventional PT-PCR,
      seems to be consistent with a previous study using real-time PCR assays in tumor
      samples. KLF6 expression levels were determined by Western blot. Compared to the
      matched surrounding tissues, a clear decrease of KLF6 protein levels in tumor
      tissues was observable (t=13.59, P<0.001). Hepatoma cell lines also showed low
      level of KLF6 protein (P<0.01) expression. Immunohistochemistry and
      immunocytochemistry showed a faint diffused staining in the HCC tissues and
      hepatoma cell lines, and endogenous KLF6 protein was detected mostly in the
      cytoplasm. KLF6 gene appeared markedly reduced in HCC tissues and hepatoma cell
      lines. Frequent down-regulation of KLF6 strongly suggested that it is a candidate
      of tumor suppressor gene for HCC.

PMID- 17550141
TI  - Primary photon fluence extraction from portal images acquired with an amorphous
      silicon flat panel detector: experimental determination of a scatter filter.
AB  - When dose delivery to the patient is evaluated by extracting the primary photon
      fluence impinging on a portal imaging device, scattered radiation from the
      patient acts as noise. Our aim in the present study is to establish and test a
      procedure to filter out scatter radiations from portal images by experimental
      determination of a scatter filtering function. We performed a dose calibration of
      the Varian (Varian Medical Systems, Palo Alto, CA) aS500 electronic portal
      imaging device in routine use in our institution. We then analyzed the collected
      data and extracted the scatter filtering function by applying a simple scatter
      model with the aid of home-made software. To check the reliability of our
      calculations we compared central axis dose values in a PMMA phantom computed
      using the extracted primary fluence with those obtained from experimental TMR(0)
      tabulated values obtaining a agreement within about 3%. We finally performed a
      check of dose delivery repeatability by calculating the dose delivered to the
      EPID during portal image acquisition for patient positioning. Delivered dose per
      MU fluctuations were within 5% over a set of images acquired during routine use
      with no prior application of any procedure aimed at optimizing dosimetric
      repeatability.

PMID- 17550142
TI  - P27 V109G Polymorphism is associated with lymph node metastases but not with
      increased risk of breast cancer.
AB  - The p27 V109G polymorphism was investigated using polymerase chain reaction
      restriction fragment length polymorphism (PCR-RFLP) method in a hospital-based
      Malaysian population. Peripheral blood samples were collected from 230 breast
      cancer patients and 200 normal and healthy women who had no history of breast
      disease or breast cancer. We evaluated the association between the p27
      polymorphism and breast cancer risk, and clinico-pathological parameters in the
      population. The distribution of genotype and allele frequencies of p27 V109G
      polymorphism were not significantly different between the breast cancer cases and
      normal subjects (P=0.376). Women who were homozygous (OR=1.73; 95% CI, 0.62-4.92)
      or heterozygous (OR=1.26; 95% CI, 0.75-2.12) for G allele, or carriers of G
      allele genotype (OR=1.34; 95%, 0.83-2.16) or G allele (OR=1.36; 95% CI, 0.90
      2.05) were not associated with breast cancer risk. No significant correlation was
      noted between G allele genotype and breast cancer risk among patients under 50
      (OR=1.28; 95% CI, 0.62-2.66) or 50 years and older (OR=1.38; 95% CI, 0.71-2.66)
      at diagnosis. The G allele genotype was significantly associated with lymph node
      metastases but independent of ER status and histological grade. In conclusion,
      the polymorphic variant at codon 109 of p27 gene may not be a marker for
      determining patients' risk of developing breast cancer but it may be a potential
      genetic marker for poor prognosis, thereby a marker for tumor prognosis.

PMID- 17550143
TI  - Unilateral retinal detachment as the initial sign of lung adenocarcinoma.
AB  - Intraocular metastases, especially to the retina, are uncommon in cancer patients
      and generally occur in an advanced phase of the disease. In patients with lung
      cancer, uveal metastases, in particular to the choroid, are the most frequent,
      and are associated mainly with small cell carcinoma or undifferentiated
      carcinoma. We report a case of unilateral retinal detachment as first sign of a
      moderately differentiated lung adenocarcinoma in a 55-year-old non-smoker that
      was admitted to the hospital for the first time complaining of a sudden visual
      loss in the superior fields of the left eye. A CT revealed a slight retinal
      enlargement of the left eye and a solid mass of about 3 centimeters behind the
      right pulmonary hilus. Bronchoscopic biopsies were performed with diagnosis of
      adenocarcinoma of the lung. The patient died after 2 months for rapid progression
      of the disease despite of combined chemotherapy treatment.

PMID- 17550144
TI  - Primary hepatic epithelioid hemangioendothelioma progressively responsive to
      interferon-alpha: is there room for novel anti-angiogenetic treatments?
AB  - Primary hepatic epithelioid hemangioendothelioma (HEH) is a rare, low-grade
      malignant neoplasm of endothelial origin, with an unpredictable clinical course
      and prognosis. No standard therapeutic strategies are still available for HEH,
      due to the infrequency of the disease and to its variable natural history that
      limit the identification of the most effective treatment. In the absence of
      metastatic disease, surgical resection or liver transplantation represent the
      treatment of choice for HEH, while several antineoplastic agents have been
      proposed in the presence of metastatic nonresectable disesase. Herein, we
      describe the biological characterization and the clinical course of a primary HEH
      progressively responsive to treatment with intermediate doses of interferon-alpha
      (IFN)-alpha2a. Furthermore, based on the newly-identified expression of endoglin
      (CD105) on HEH, we discuss the clinical potential of novel anti-angiogenetic
      approaches to the disease.

PMID- 17550145
TI  - Pulmonary artery sarcoma: an insidious tumor still diagnosed too late. Analysis
      of the literature and report of a case.
AB  - Pulmonary artery sarcoma is an exceptionally rare tumor which must be considered
      in the differential diagnosis of pulmonary thromboembolism. We report the case of
      a 36-year-old woman and review 100 cases published in the literature between 1988
      and 2005. The patient presented with a history of dyspnea, fatigue, fever, night
      sweats and anemia that did not respond to antibiotic therapy. She also had
      hemoptysis. Transvenous catheter biopsy was indicative of sarcoma. A left
      pneumonectomy was performed, followed by five cycles of chemotherapy.
      Histological and immunohistochemical studies documented an intimal sarcoma with
      myofibroblastic differentiation. The patient is alive and well 20 months after
      surgery. The clinico-pathological features of pulmonary artery sarcoma are
      described.

PMID- 17550146
TI  - A case of clear renal cell cancer associated to meningioma and verrucous
      carcinoma of frontal region in an old patient.
AB  - Here we report the concomitant development in an 82 year-old patient of three
      different neoplasms with different histology, degree of differentiation and
      clinical aggressiveness. In fact, the patient presented a verrucous carcinoma
      with unusual location at her head frontal region and a concomitant calcified
      meningioma of the frontal region of the brain. At the moment of the examination
      also a clear renal cell carcinoma, that was the cause of patient decease, was
      discovered. At our knowledge, this is the first case of concomitant presentation
      of these three tumours. Even if the present case was not correlated with any
      hereditary feature the presence of a genetic predisposition common to all the
      three tumours can not be excluded, but the casual co-existence of different both
      genetic and environmental factors can be also suggested.

PMID- 17550147
TI  - Compensating for miter bends in cylindrical tubing.
AB  - Miter bends in cylindrical tubing perturb wave propagation in a way that may
      alter the desired resonance properties in musical instruments. The nature of the
      perturbations and several methods of compensating for them at low frequencies are
      described.

PMID- 17550148
TI  - Acoustic cues available for ranging by humpback whales.
AB  - Field measurements of sound propagation in a humpback whale habitat were
      collected to identify cues that a humpback whale might use to estimate its
      distance from sound sources. The data show that spectral cues are sufficient for
      estimating the relative distance a sound has traveled in such environments, and
      that several other cues may also provide useful information. It is suggested that
      listening humpback whales may use multiple cues in parallel to determine the
      range to singing whales.

PMID- 17550149
TI  - An efficient high-order algorithm for acoustic scattering from penetrable thin
      structures in three dimensions.
AB  - This paper presents a high-order accelerated algorithm for the solution of the
      integral-equation formulation of volumetric scattering problems. The scheme is
      particularly well suited to the analysis of "thin" structures as they arise in
      certain applications (e.g., material coatings); in addition, it is also designed
      to be used in conjunction with existing low-order FFT-based codes to upgrade
      their order of accuracy through a suitable treatment of material interfaces. The
      high-order convergence of the new procedure is attained through a combination of
      changes of parametric variables (to resolve the singularities of the Green
      function) and "partitions of unity" (to allow for a simple implementation of
      spectrally accurate quadratures away from singular points). Accelerated
      evaluations of the interaction between degrees of freedom, on the other hand, are
      accomplished by incorporating (two-face) equivalent source approximations on
      Cartesian grids. A detailed account of the main algorithmic components of the
      scheme are presented, together with a brief review of the corresponding error and
      performance analyses which are exemplified with a variety of numerical results.

PMID- 17550150
TI  - Generation of shock-free pressure waves in shaped resonators by boundary driving.
AB  - Investigation of high amplitude pressure oscillations generated by boundary
      driving in shaped resonators has been carried out both theoretically and
      experimentally. In the theoretical modeling, the acoustic resonance in an
      axisymmetric resonator is studied by the Galerkin method. The resonator is
      exponentially expanded and the boundary driving is provided by a piston at one
      end. The pressure wave forms, amplitudes, resonance frequencies, and ratio of
      pressures at the two ends of the resonator are calculated for various expansion
      flare constants and driving strengths. These results are partially compared with
      those generated by shaking the resonator. They are also verified in the
      experiment, in which an exponentially expanded resonator is connected to a
      speaker box functioning as the piston. The experiment is further extended to a
      horn-shaped resonator with a rectangular cross section. The boundary driving in
      this case is generated by a circular piezoelectric disk, which forms one sidewall
      of the resonator cavity. The characteristics of axisymmetric resonators, such as
      the resonance frequency and amplitude ratio of pressures at the two ends, are
      observed in this low aspect ratio rectangular resonator with the sidewall
      driving.

PMID- 17550151
TI  - Comparison of measurements and predictions of sound propagation in a valley-slope
      configuration in an inhomogeneous atmosphere.
AB  - Mountainous areas form a very specific context for sound propagation: There is a
      particular ground effect and meteorological conditions are often extreme. In this
      paper, detailed sound propagation calculations are compared to noise measurements
      accompanied by meteorological observations. The sound source considered is road
      traffic along the center axis of a valley. Noise levels were measured in two
      cross sections, at three locations each: one on the valley floor and two on the
      slopes, up to 166 m above the source. For the numerical calculations, the rotated
      Green's function parabolic equation method is used, taking into account the
      undulation of the terrain and an inhomogeneous atmosphere. Typical parameters of
      this method were optimized for computational efficiency. Predictions agree with
      measurements to within 3 dBA up to propagation distances of 1 km, in windless
      conditions. The calculations further show that the terrain profile is responsible
      for an increase in sound pressure level at distant, elevated points up to 30 dBA
      compared to a flat ground situation. Complex temperature profiles account for
      level changes between -3 dBA and +10 dBA relative to a homogeneous atmosphere.
      This study shows that accurate sound level prediction in a valley-slope
      configuration requires detailed numerical calculations.

PMID- 17550152
TI  - Acoustic monitoring of the tide height and slope-water intrusion at the New
      Jersey Shelf in winter conditions.
AB  - Waveguide invariant theory is used to describe the frequency shifts of constant
      acoustic intensity level curves in broadband signal spectrograms measured at the
      New Jersey Shelf during the winter of 2003. The broadband signals (270-330 Hz)
      were transmitted from a fixed source and received at three fixed receivers,
      located at 10, 20, and 30 km range along a cross-shelf propagation track. The
      constant acoustic intensity level curves of the received signals indicate regular
      frequency shifts that can be well predicted by the change in water depth observed
      through tens of tidal cycles. A second pattern of frequency shifts is observed at
      only 30 km range where significant variability of slope-water intrusion was
      measured. An excellent agreement between observed frequency shifts of the
      constant acoustic intensity levels and those predicted by the change in tide
      height and slope water elevations suggests the capability of long-term acoustic
      monitoring of tide and slope water intrusions in winter conditions.

PMID- 17550153
TI  - Statistical description of chaotic rays in a deep water acoustic waveguide.
AB  - This paper analyzes the chaotic ray dynamics at multimegater ranges in a deep
      water environment with internal-wave-induced fluctuations of the sound speed. The
      behavior of acoustic ray paths is investigated using the Hamiltonian formalism
      expressed in terms of action-angle variables. It is shown that the range
      dependence of the action variable of chaotic ray can be approximated by a random
      Wiener process. On the basis of this result an approximate statistical
      description of the chaotic ray structure is derived. Distributions of
      coordinates, momenta (grazing angles), and actions of sound rays are evaluated.
      This statistical approach is used for studying ray travel times, that is, arrival
      times of sound pulses coming to the receiver through different ray paths. The
      spread of travel times for a bundle of rays with close starting parameters and
      the influence of sound speed fluctuations on the timefront representing ray
      arrivals in the time-depth plane are examined. Estimates for the widening and
      bias of the timefront segment caused by the fluctuations are obtained.

PMID- 17550154
TI  - Frequency dependencies of phase velocity and attenuation coefficient in a water
      saturated sandy sediment from 0.3 to 1.0 MHz.
AB  - The frequency-dependent phase velocity and attenuation coefficient for the fast
      longitudinal wave in a water-saturated sandy sediment were measured over the
      frequency range from 0.3 to 1.0 MHz. The experimental data of phase velocity
      exhibited the significant negative dispersion, with the mean rate of decline of
      120 +/- 20 m/s/MHz. The Biot model predicted the approximately nondispersive
      phase velocity and the grain-shearing (GS) model exhibited the slightly positive
      dispersion. In contrast, the predictions of the multiple scattering models for
      the negative dispersion in the glass-grain composite were in general agreement
      with the experimental data for the water-saturated sandy sediment measured here.
      The experimental data of attenuation coefficient was found to increase
      nonlinearly with frequency from 0.3 to 1.0 MHz. However, both the Biot and the GS
      models yielded the attenuation coefficient increasing almost linearly with
      frequency. The total attenuation coefficient given by the algebraic sum of
      absorption and scattering components showed a reasonable agreement with the
      experimental data for overall frequencies. This study suggests that the
      scattering is the principal mechanism responsible for the variations of phase
      velocity and attenuation coefficient with frequency in water-saturated sandy
      sediments at high frequencies.

PMID- 17550155
TI  - Diversity in ambient noise in European freshwater habitats: noise levels,
      spectral profiles, and impact on fishes.
AB  - The detectability of acoustic signals depends on the hearing abilities of
      receivers and the prevailing ambient noise in a given habitat. Ambient noise is
      inherent in all terrestrial and aquatic habitats and has the potential to
      severely mask relevant acoustic signals. In order to assess the detectability of
      sounds to fishes, the linear equivalent sound pressure levels (L(Leq)) of twelve
      European freshwater habitats were measured and spectra of the ambient noise
      recordings analyzed. Stagnant habitats such as lakes and backwaters are quiet,
      with noise levels below 100 dB re 1 microPa (L(Leq)) under no-wind conditions.
      Typically, most environmental noise is concentrated in the lower frequency range
      below 500 Hz. Noise levels in fast-flowing waters were typically above 110 dB and
      peaked at 135 dB (Danube River in a free-flowing area). Contrary to stagnant
      habitats, high amounts of sound energy were present in the high frequency range
      above 1 kHz, leaving a low-energy "noise window" below 1 kHz. Comparisons between
      the habitat noise types presented here and prior data on auditory masking
      indicate that fishes with enhanced hearing abilities are only moderately masked
      in stagnant, quiet habitats, whereas they would be considerably masked in fast
      flowing habitats.

PMID- 17550156
TI  - Bayesian focalization: quantifying source localization with environmental
      uncertainty.
AB  - This paper applies a Bayesian formulation to study ocean acoustic source
      localization as a function of uncertainty in environmental properties (water
      column and seabed) and of data information content [signal-to-noise ratio (SNR)
      and number of frequencies]. The approach follows that of the optimum uncertain
      field processor [A. M. Richardson and L. W. Nolte, J. Acoust. Soc. Am. 89, 2280
      2284 (1991)], in that localization uncertainty is quantified by joint marginal
      probability distributions for source range and depth integrated over uncertain
      environmental properties. The integration is carried out here using Metropolis
      Gibbs' sampling for environmental parameters and heat-bath Gibbs' sampling for
      source location to provide efficient sampling over complicated parameter spaces.
      The approach is applied to acoustic data from a shallow-water site in the
      Mediterranean Sea where previous geoacoustic studies have been carried out. It is
      found that reliable localization requires a sufficient combination of prior
      (environmental) information and data information. For example, sources can be
      localized reliably for single-frequency data at low SNR (-3 dB) only with small
      environmental uncertainties, whereas successful localization with large
      environmental uncertainties requires higher SNR and/or multifrequency data.

PMID- 17550157
TI  - Acoustic propagation under tidally driven, stratified flow.
AB  - Amplitude and phase variability in acoustic fields are simulated within a
      canonical shelf-break ocean environment using sound speed distributions computed
      from hydrodynamics. The submesoscale description of the space and time varying
      environment is physically consistent with tidal forcing of stratified flows over
      variable bathymetry and includes the generation, evolution and propagation of
      internal tides and solibores. For selected time periods, two-dimensional acoustic
      transmission examples are presented for which signal gain degradation is computed
      between 200 and 500 Hz on vertical arrays positioned both on the shelf and beyond
      the shelf break. Decorrelation of the field is dominated by the phase
      contribution and occurs over 2-3 min, with significant recorrelation often noted
      for selected frequency subbands. Detection range is also determined in this
      frequency band. Azimuth-time variations in the acoustic field are illustrated for
      100 Hz sources by extending the acoustic simulations to three spatial dimensions.
      The azimuthal and temporal structure of both the depth-averaged transmission loss
      and temporal correlation of the acoustic fields under different environmental
      conditions are considered. Depth-averaged transmission loss varies up to 4 dB,
      depending on a combination of source depth, location relative to the slope and
      tidally induced volumetric changes in the sound speed distribution.

PMID- 17550158
TI  - Single-crystal lead magnesium niobate-lead titanate (PMN/PT) as a broadband high
      power transduction material.
AB  - Two experimental underwater acoustic projectors, a tonpilz array, and a
      cylindrical line array, were built with single crystal, lead magnesium
      niobate/lead titanate, a piezoelectric transduction material possessing a large
      electromechanical coupling factor (k33 = 0.9). The mechanical quality factor,
      Q(m), and the effective coupling factor, k(eff), determine the frequency band
      over which high power can be transmitted; k(eff) cannot be greater than the
      piezoelectric material value, and so a high material coupling factor is a
      requisite for broadband operation. Stansfield's bandwidth criteria are used to
      calculate the optimum Q(m) value, Q(opt) approximately 1.2 (1-k(eff)2 1/2/k(eff).
      The results for the tonpilz projector exhibited k(eff) = 0.730, Q(m) = 1.17 (very
      near optimal), and a fractional bandwidth of 0.93. For the cylindrical transducer
      array, k(eff) = 0.867, Q(m) = 0.91 (larger than the optimum value, 0.7), and the
      bandwidth was 1.16. Although the measured bandwidths were less than optimal, they
      were accurately predicted by the theory, despite the highly simplified nature of
      the Van Dyke equivalent circuit, on which the theory is based.

PMID- 17550159
TI  - Acoustic modes propagating along the free surface of granular media.
AB  - In unconsolidated granular materials under gravity there exist acoustical waves
      propagating along the surface with anomalously low sound velocity. The presented
      theory describes these guided surface acoustic modes (GSAM) confined between the
      surface of the granular materials and in-depth layers with increasing rigidity.
      The analysis is based on the obtained original analytical solution of the
      Helmholtz equation that has never been used both in classical and quantum
      mechanics. This solution is valid for a particular rigidity profile, whereas the
      general case of grains with or without adhesion has been analyzed numerically. In
      contrast to the Rayleigh wave polarized in the sagittal (vertical) plane, which
      is the unique localized mode in a homogeneous solid, an infinite number of modes
      with sagittal polarization as well as an infinite number of shear horizontal
      modes have been found. The difference in physical mechanisms of localization is
      discussed, and the transformation of the GSAMs into the Rayleigh wave at the
      increasing adhesion is demonstrated: The first sagittal mode transforms into the
      Rayleigh one, while the others delocalize. The theory explains the experimentally
      observed magnitude of velocity for the acoustic waves in sand elliptically
      polarized in the sagittal plane.

PMID- 17550160
TI  - Ultrasonic oil-film thickness measurement: an angular spectrum approach to assess
      performance limits.
AB  - The performance of ultrasonic oil-film thickness measurement in a ball bearing is
      quantified. A range of different viscosity oils (Shell T68, VG15, and VG5) are
      used to explore the lowest reflection coefficient and hence the thinnest oil-film
      thickness that the system can measure. The results show a minimum reflection
      coefficient of 0.07 for both oil VG15 and VG5 and 0.09 for oil T68 at 50 MHz.
      This corresponds to an oil-film thickness of 0.4 microm for T68 oil. An angular
      spectrum (or Fourier decomposition) approach is used to analyze the performance
      of this configuration. This models the interaction of component plane waves with
      the measurement system and quantifies the effect of the key parameters
      (transducer aperture, focal length, and center frequency). The simulation shows
      that for a focused transducer the reflection coefficient tends to a limiting
      value at small oil-film thickness. For the transducer used in this paper it is
      shown that the limiting reflection coefficient is 0.05 and the oil-film
      measurement errors increase as the reflection coefficient approaches this value.
      The implications for improved measurement systems are then discussed.

PMID- 17550161
TI  - Measurement of focused ultrasonic fields using a scanning laser vibrometer.
AB  - With the development of optical techniques, scanning laser vibrometers have been
      applied successfully in measuring particle velocities and distributions in
      ultrasonic fields. In this paper, to develop the optical interferometry in
      measuring focused fields with small amplitude, the "effective" refractive index
      used for plane waves and extended for spherical waves is presented, the piezo
      optic effect as a function of the incident angle of the laser beam is simulated,
      and the ultrasonic field produced by a concave spherical transducer is calculated
      numerically around its focal region. To verify the feasibility of the optical
      method in detecting focused ultrasonic fields, a measurement system was set up
      that utilized both a scanning laser vibrometer and a membrane hydrophone.
      Measurements were made in different zones of a focusing transducer, and good
      results were acquired from the optical interferometry in regions where acoustic
      waves travel in plane form or spherical form. The data obtained from the optical
      method are used to reconstruct acoustic fields, and it is found that the focal
      plane, the maximum pressure, and the beamwidth of the transducer can be
      forecasted accurately.

PMID- 17550162
TI  - On experimental determination of the random-incidence response of microphones.
AB  - The random-incidence sensitivity of a microphone is defined as the ratio of the
      output voltage to the sound pressure that would exist at the position of the
      acoustic center of the microphone in the absence of the microphone in a sound
      field with incident plane waves coming from all directions. The random-incidence
      correction of a number of laboratory standard microphones has been determined
      experimentally. Although the measurement procedure seems to be straightforward,
      some practical and fundamental problems arise: (i) Reflections from the mounting
      rig contaminate the measured frequency response, and whereas some of these
      reflections can be removed using a time-selective technique, others coincide with
      the direct impulse response and consequently cannot be removed in the time domain
      and thus affect the accuracy of the estimate; (ii) the accuracy of the estimate
      is relying on the rotational symmetry of the microphone and depends on the
      angular resolution. The effect of the angular resolution has been compared with
      the analytical solution of the scattering and diffraction around a solid sphere.
      Numerical calculations supplement the experimental results. Although the
      procedure has only been applied to laboratory standard microphones, it is not
      restricted to such microphones and may be applied to other types of measurement
      microphones.

PMID- 17550163
TI  - Extracting the Green's function of attenuating heterogeneous acoustic media from
      uncorrelated waves.
AB  - The Green's function of acoustic or elastic wave propagation can, for loss-less
      media, be retrieved by correlating the wave field that is excited by random
      sources and is recorded at two locations. Here the generalization of this idea to
      attenuating acoustic waves in an inhomogeneous medium is addressed, and it is
      shown that the Green's function can be retrieved from waves that are excited
      throughout the volume by spatially uncorrelated injection sources with a power
      spectrum that is proportional to the local dissipation rate. For a finite volume,
      one needs both volume sources and sources at the bounding surface for the
      extraction of the Green's functions. For the special case of a homogeneous
      attenuating medium defined over a finite volume, the phase and geometrical
      spreading of the Green's function is correctly retrieved when the volume sources
      are ignored, but the attenuation is not.

PMID- 17550164
TI  - Discomfort from sinusoidal oscillation in the roll and lateral axes at
      frequencies between 0.2 and 1.6 Hz.
AB  - Discomfort caused by low frequency lateral and roll oscillations is often
      predicted from lateral acceleration in the plane of the seat, irrespective of
      whether it comes from horizontal motion or a component of gravity arising from
      roll. This study investigated discomfort from lateral and roll oscillation and
      whether acceleration in the plane of a seat predicts discomfort. Twelve subjects,
      sitting with and without backrest, used magnitude estimation to judge sinusoidal
      oscillations in the roll and lateral axes at ten frequencies between 0.2 and 1.6
      Hz at magnitudes between 0.063 and 0.63 m s(-2) root mean square. The rate of
      growth of vibration discomfort with increasing magnitude reduced with increasing
      frequency, so the frequency-dependence of discomfort varied with magnitude.
      Acceleration in the plane of the seat predicted discomfort from both lateral and
      roll oscillation at frequencies less than 0.4 Hz. At higher frequencies,
      acceleration produced by roll oscillation resulted in greater discomfort than the
      same acceleration produced by lateral oscillation. At frequencies greater than
      0.4 Hz, a full height backrest increased discomfort with both lateral and roll
      oscillation. The prediction of discomfort caused by low frequency lateral and
      roll oscillation requires that both components are measured and assessed
      according to their separate effects.

PMID- 17550165
TI  - Frequency- and time-domain asymptotic fields near the critical cone in fluid
      fluid configuration.
AB  - Near the critical cone of a point source placed at the interface between two half
      space fluid media, investigation is made of the asymptotic fields in the
      frequency domain and their synthetic wave forms in the time domain. While the
      leading-order (and the head-wave) components give a good description of the true
      fields well off the critical cone, the uniform asymptotic (UA) analysis has to be
      made for the approximation near the critical cone. The UA analysis splits into
      two cases, depending on the medium densities and wave speeds. For Case 1, the UA1
      approximation is employed that takes into account the proximity of the stationary
      phase point to the branch point. In Case 2, the UA2 approximation is employed in
      which consideration is also given to the proximity of the stationary point to the
      pole and to the combined effect of the stationary point, the branch point, and
      the pole. The validities of the asymptotic fields are checked in the time domain
      by comparing the asymptotic field wave forms against the wave-number-synthetic
      wave forms. The UA fields show good accuracy and causal behaviors, with the
      causality of the UA2 fields previously unreported in the literature.

PMID- 17550166
TI  - Detection and localization of rib detachment in thin metal and composite plates
      by inversion of laser Doppler vibrometry scans.
AB  - The laboratory implementation of a fault detection and localization method based
      on inversion of dynamic surface displacements measured by a scanned laser Doppler
      vibrometer (SLDV) was investigated. The technique uses flexural wave and
      generalized force inversion algorithms which have previously been demonstrated
      using simulated noise-free vibration data generated for thick plates with a
      finite element model. Here these inversion algorithms to SLDV measurements made
      in the laboratory on a thin nickel plate and a thin carbon fiber composite plate,
      both having attached reinforcing ribs with intentional de-bonding of the
      rib/plate interface at a specific location on each structure are applied. The
      inverted displacement maps clearly detect and locate the detachment, whereas
      direct observation of the surface displacements does not. It is shown that the
      technique is relatively robust to the choice of frequency and to the presence of
      noise.

PMID- 17550167
TI  - Noise in the operating rooms of Johns Hopkins Hospital.
AB  - Very little reliable information exists on the sound levels present in an
      operating room environment. To remedy this situation, sound pressure levels of
      the operating rooms in Johns Hopkins Hospital were monitored before, during, and
      after operations. The data were analyzed to determine background sound levels,
      average equivalent sound levels L(eq), frequency distribution, and peak sound
      pressure levels L(peak). Each surgery was matched to the period of noise it
      produced permitting the association of sound levels with particular types of
      surgeries and the determination of various sound measures for classes of surgery
      (e.g., orthopedic, neurological, etc.). Averaging over many surgeries, orthopedic
      surgery was found to have the highest L(eq) at approximately 66 dB(A).
      Neurosurgery, urology, cardiology, and gastrointestinal surgery followed closely,
      ranging from 62 to 65 dB(A). By considering the L(peak) along with the L(eq)
      values, a pattern emerges for the various surgical divisions. Gastrointestinal
      and thoracic surgery are relatively quiet among the surgical divisions.
      Neurosurgery and orthopedics have sustained high sound levels. Cardiology surgery
      has a more moderate average sound level but includes brief periods of extremely
      high peak sound levels. For neurosurgery and orthopedic surgery, peak levels
      exceeded 100 dB over 40% of the time. The highest peak levels routinely seen
      during surgery were well in excess of 120 dB.

PMID- 17550168
TI  - Noise in contemporary neonatal intensive care.
AB  - Weekly sound surveys (n = 63) were collected, using 5 s sampling intervals, for
      two modern neonatal intensive care units (NICUs). Median weekly equivalent sound
      pressure levels (LEQ) for NICU A ranged from 61 to 63 dB (A weighted), depending
      on the level of care. NICU B L(EQ) measurements ranged from 55 to 60 dB (A
      weighted). NICU B was recently built with a focus on sound abatement, explaining
      much of the difference between the two NICUs. Sound levels exceeded 45 dB (A
      weighted), recommended by the American Academy of Pediatrics, more than 70% of
      the time for all levels of care. Hourly L(EQ)s below 50 dB (A weighted) and
      hourly L10s below 55 dB (A weighted), recommended by the Sound Study Group (SSG)
      of the National Resource Center, were also exceeded in more than 70% of recorded
      samples. A third SSG recommendation, that the 1 s L(MAX), should not exceed 70 dB
      (A weighted), was exceeded relatively infrequently (< 11% of the time). Peak
      impulse measurements exceeded 90 dB for 6.3% of 5 s samples recorded from NICU A
      and 2.8% of NICU B samples. Twenty-four h periodicities in sound levels as a
      function of regular staff activities were apparent, but short-term variability
      was considerable.

PMID- 17550169
TI  - Chronological analysis of architectural and acoustical indices in music
      performance halls.
AB  - This study aims to identify the changes in architectural and acoustical indices
      in halls for music performance built in the 18th through the 20th Centuries.
      Seventy-one halls are classified in five specific periods from the Classical
      Period (1751-1820) to the Contemporary Period (1981-2000) based on chronology in
      music and architectural acoustics. Architectural indices such as room shape,
      seating capacity, room volume, balcony configuration, and the like as well as
      acoustical indices such as RT, EDT, G, C80, IACC, and the like for the halls
      found in the literature are chronologically tabulated and statistically analyzed
      to identify trends and relationships in architectural and acoustical design for
      each of the historical periods identified. Some indices appear correlated with
      each other.

PMID- 17550170
TI  - Measurement of sound power and absorption in reverberation chambers using energy
      density.
AB  - Reverberation chamber measurements typically rely upon spatially averaged squared
      pressure for the calculation of sound absorption, sound power, and other acoustic
      values. While a reverberation chamber can provide an approximately diffuse sound
      field, variations in sound pressure consistently produce uncertainty in
      measurement results. This paper explores the benefits of using total energy
      density or squared particle velocity magnitude (kinetic energy density) instead
      of squared pressure (potential energy density) for sound absorption and sound
      power measurements. The approaches are based on methods outlined in current ISO
      standards. The standards require a sufficient number of source-receiver locations
      to obtain suitable measurement results. The total and kinetic energy densities
      exhibit greater spatial uniformity at most frequencies than potential energy
      density, thus requiring fewer source-receiver positions to produce effective
      results. Because the total energy density is typically the most uniform of the
      three quantities at low frequencies, its use could also impact the usable low
      frequency ranges of reverberation chambers. In order to employ total and kinetic
      energy densities for sound absorption measurements, relevant energy-based impulse
      responses were developed as part of the work for the assessment of sound field
      decays.

PMID- 17550171
TI  - Analysis of the performance of a particle velocity sensor between two cylindrical
      obstructions.
AB  - The performance of an acoustic particle velocity sensor that is placed between
      two cylindrical objects has been analyzed both analytically and by means of
      finite volume simulations on fluid dynamics. The results are compared with
      acoustic experiments that show a large magnification of the output signal of the
      particle velocity sensor due to the mounting of the sensor between two cylinders.
      The influences of this construction consist of an attenuation of particle
      velocities at frequencies below a few hertz, whereas signals in the higher
      frequency range are amplified, up to approximately three times (10 dB) in a
      frequency range between 50 and 1000 Hz. The theoretical analysis is based on the
      derivation of the stream function for the situation of two long cylinders
      immersed in an oscillating incompressible viscous fluid, at low Reynolds numbers.
      The results lead to an improved insight into the effects of viscosity and fluid
      flow that play a role in acoustic measurements and open the way for further
      optimization of the sensitivity of the sensor.

PMID- 17550172
TI  - Blind identification of aggregated microphones in time domain.
AB  - This paper introduces an algorithm for blind identification of aggregated
      microphones in time domain. The features of our approach are summarized as
      follows: (1) The proposed method treats the blind identification problem of
      anechoic mixtures in the time domain. (2) The proposed method can identify the
      gain of each microphone for the directions of sounds whose number is more than
      the number of the microphones. (3) The proposed method does not utilize the
      statistical independence of the sounds. The sounds may be not only statistically
      independent but may also be statistically dependent. (4) The proposed method
      treats the partially disjoint sounds in the time domain. The sounds may overlap
      in the frequency domain unlike the sparseness approach. (5) The proposed method
      does not need to estimate the intervals where sounds are disjoint. First, it is
      shown that the problem of blind identification and blind source separation can be
      described not as a convolutive model, but as an instantaneous model in the case
      of the anechoic mixing when aggregated microphones are assumed. The necessary
      conditions and the algorithm with experimental results are also described.

PMID- 17550173
TI  - Multiaspect target detection via the infinite hidden Markov model.
AB  - A new multiaspect target detection method is presented based on the infinite
      hidden Markov model (iHMM). The scattering of waves from a target is modeled as
      an iHMM with the number of underlying states treated as infinite, from which a
      full posterior distribution on the number of states associated with the targets
      is inferred and the target-dependent states are learned collectively. A set of
      Dirichlet processes (DPs) are used to define the rows of the HMM transition
      matrix and these DPs are linked and shared via a hierarchical Dirichlet process.
      Learning and inference for the iHMM are based on a Gibbs sampler. The basic
      framework is applied to a detailed analysis of measured acoustic scattering data.

PMID- 17550174
TI  - Noise propagation in linear and nonlinear inverse scattering.
AB  - The propagation of noise from the data to the reconstructed speed of sound image
      by inverse scattering within the framework of the Lippmann-Schwinger integral
      equation of scattering is discussed. The inversion algorithm that was used
      consisted in minimizing a Tikhonov functional in the unknown speed of sound. The
      gradient of the objective functional was computed by the method of the adjoint
      fields. An analytical expression for the inverse scattering covariance matrix of
      the image noise was derived. It was shown that the covariance matrix in the
      linear x-ray computed tomography is a special case of the inverse scattering
      matrix derived in this paper. The matrix was also analyzed in the limit of the
      linearized Born approximation, and the results were found to be in qualitative
      agreement with those recently reported in the literature for Born inversion using
      filtered backpropagation algorithm. Finally, the applicability of the analysis
      reported here to the obstacle problem and the physical optics approximation was
      discussed.

PMID- 17550175
TI  - Boundary element method for the acoustic characterization of a machine in bounded
      noisy environment.
AB  - In this article, a boundary element method is used to recover free field
      conditions from noisy bounded space situations. The proposed approach is based on
      the Helmholtz integral formulation. The method requires the knowledge of double
      layer pressure fields on two parallel closed surfaces surrounding the source.
      First, the outgoing and ingoing pressure field are separated using Helmholtz
      integral. Then, the incident field scattered by the tested source is subtracted
      from the outgoing field to recover the pressure field which would have been
      radiated in free space. To simplify the process, rigid body approximation for the
      source is used. The method is numerically tested in the following conditions: the
      chosen sound source is the upper spherical cap of a rigid sphere, the source is
      located at the center of a rigid spherical cavity, and a monopole secondary
      source is added to blur the primary pressure field. Simulations give good results
      for ka up to 5 when the discretization of the surfaces is sufficient.

PMID- 17550176
TI  - A mechano-electro-acoustical model for the cochlea: response to acoustic stimuli.
AB  - A linear, physiologically based, three-dimensional finite element model of the
      cochlea is developed. The model integrates the electrical, acoustic, and
      mechanical elements of the cochlea. In particular, the model includes
      interactions between structures in the organ of Corti (OoC), piezoelectric
      relations for outer hair cell (OHC) motility, hair bundle (HB) conductance that
      changes with HB deflection, current flow in the cross section and along the
      different scalae, and the feed-forward effect. The parameters in the model are
      based on guinea-pig data as far as possible. The model is vetted using a variety
      of experimental data on basilar membrane motion and data on voltages and currents
      in the OoC. Model predictions compare well, qualitatively and quantitatively,
      with experimental data on basilar membrane frequency response, impulse response,
      frequency glides, and scala tympani voltage. The close match of the model
      predictions with experimental data demonstrates the validity of the model for
      simulating cochlear response to acoustic input and for testing hypotheses of
      cochlear function. Analysis of the model and its results indicates that OHC
      somatic motility is capable of powering active amplification in the cochlea. At
      the same time, the model supports a possible synergistic role for HB motility in
      cochlear amplification.

PMID- 17550177
TI  - Scala vestibuli pressure and three-dimensional stapes velocity measured in direct
      succession in gerbil.
AB  - It was shown that the mode of vibration of the stapes has a predominant piston
      component but rotations producing tilt of the footplate are also present. Tilt
      and piston components vary with frequency. Separately it was shown that the
      pressure gain between ear canal and scala vestibuli was a remarkably flat and
      smooth function of frequency. Is tilt functional contributing to the pressure in
      the scala vestibuli and helping in smoothing the pressure gain? In experiments on
      gerbil the pressure in the scala vestibuli directly behind the footplate was
      measured while recording simultaneously the pressure produced by the sound source
      in the ear canal. Successively the three-dimensional motion of the stapes was
      measured in the same animal. Combining the vibration measurements with an
      anatomical shape measurement from a micro-CT (CT: computed tomography) scan the
      piston-like motion and the tilt of the footplate was calculated and correlated to
      the corresponding scala vestibuli pressure curves. No evidence was found for the
      hypothesis that dips in the piston velocity are filled by peaks in tilt in a
      systematic way to produce a smooth middle ear pressure gain function. The present
      data allowed calculations of the individual cochlear input impedances.

PMID- 17550178
TI  - Basilar membrane mechanics in the 6-9 kHz region of sensitive chinchilla
      cochleae.
AB  - The vibration of the basilar membrane in the 6-9 kHz region in the chinchilla
      cochlea has been studied using a displacement sensitive interferometer.
      Displacements of 0.7-1.4 nm at 0 dB sound pressure level have been obtained. At
      the characteristic frequency (CF), rate-of-growth (ROG) functions computed as the
      slope of input-output (IO) functions can be as low as 0.1 dB/dB. IO functions for
      frequencies > CF have ROGs near 0 dB/dB and can have notches characterized by
      both negative slopes and expansive ROGs, i.e., > 1 dB/dB. For frequencies <
      0.6*CF, ROGs > 1.2 dB/dB were found. Cochlear gain is shown to be greater than 60
      dB in sensitive preparations with a single cochlea having nearly 80 dB gain. The
      compressive nature of the cochlea remains at all levels though it is masked at
      frequencies > CF when the amplitude of a compression wave exceeds that of the
      traveling wave. The compression wave produces the plateau region of the
      mechanical response at high intensities and has a nearly constant phase versus
      frequency function implying a high velocity. The summation of the traveling and
      compression waves explains the occurrence of the notches in both the IO and iso
      intensity functions. Vibration of the osseous spiral limbus may alter the drive
      to inner hair cells.

PMID- 17550179
TI  - Mutual suppression in the 6 kHz region of sensitive chinchilla cochleae.
AB  - Basilar membrane (BM) vibration was measured using a displacement measuring
      interferometer for single-tone and two-tone suppression (2TS) paradigms in the 6
      9 kHz region of sensitive chinchilla cochleae that had gains near or better than
      60 dB. Based on prior studies of basilar membrane vibration, three significant
      differences remain between BM and auditory nerve (AN) 2TS responses: (1)
      suppression thresholds in the tail of tuning curves were much higher in BM than
      the auditory nerve (AN); (2) rates of suppression were significantly higher in AN
      than BM; and (3) the amplitude of vibration with low-frequency suppressors was
      always greater than the single-tone displacement rendering it impossible to
      explain 2TS rate suppression in the AN. The first two differences are eliminated
      by the results of the present study while the third remains. Suppression
      amplitudes greater than 40 dB and rates of suppression larger than 2.5 dB/dB were
      found for low-frequency suppressors. A correlation between both the gain and
      nonlinearity of the cochlea and 2TS properties indicates that when sensitive
      cochleae are studied. The third difference between BM and AN behavior could be
      strictly a function of the high-pass filter characteristic of the inner hair
      cells.

PMID- 17550180
TI  - Forward and reverse waves in nonclassical models of the cochlea.
AB  - In "classical" models of the cochlea the mechanical properties of the cochlear
      partition (in which the basilar membrane plays a dominant role) depend only on
      the local longitudinal coordinate. Wave propagation in such models is the same
      for both propagation directions, towards the apex and towards the base.
      "Nonclassical" models contain mechanical properties that depend on variables at
      more than one location. In such models the properties of wave propagation may
      well be asymmetrical. This note presents an analysis of feed-forward and feed
      backward models, with the emphasis on the properties of forward and reverse
      waves. In both of these classes of model, wave amplification for forward waves
      turns into wave attenuation for reverse waves. The slope of the phase pattern is
      nearly the same for the two types of waves, it is increased in feed-forward
      models and decreased in feed-backward models-with respect to a model without
      feedback.

PMID- 17550181
TI  - Contributions of individual components to the overall loudness of a multitone
      complex.
AB  - The contributions of individual components to the overall loudness of a multitone
      complex were examined in a two-interval, loudness judgment task. Stimuli were
      five-tone complexes centered on 1000 Hz, with six different logarithmic frequency
      spacings, corresponding to bandwidths from 46 to 2119 Hz. Stimuli were presented
      for 300 ms (10 ms rise/fall). The overall level of the standard complex was fixed
      at 60 dB SPL (53 dB/component). Levels of the individual components of the
      comparison complex were selected at random from a rectangular distribution with a
      range of 20 dB. Perceptual weights were computed by calculating the point
      biserial correlation between the difference in the level of each component across
      the two intervals and the subject's response. When all components fell within the
      same critical band, weights varied little across components. In contrast, the
      range of weights increased with increasing frequency separation, with more weight
      given to the lowest and highest frequency components. A relation between
      component weight and masked threshold was observed for all but the widest spacing
      condition. Perceptual weights and masked thresholds were largely in agreement
      with the loudness model [Moore et al., J. Audio. Eng. Soc. 45, 224-237 (1997)],
      except at the widest bandwidth.

PMID- 17550182
TI  - The effects of low- and high-frequency suppressors on psychophysical estimates of
      basilar-membrane compression and gain.
AB  - Physiological studies suggest that the increase in suppression as a function of
      suppressor level is greater for a suppressor below than above the signal
      frequency. This study investigated the pattern of gain reduction underlying this
      increase in suppression. Temporal masking curves (TMCs) were obtained by
      measuring the level of a 2.2-kHz sinusoidal off-frequency masker or 4-kHz on
      frequency sinusoidal masker required to mask a brief 4-kHz sinusoidal signal at
      10 dB SL, for masker-signal intervals of 20-100 ms. TMCs were also obtained in
      the presence of a 3- or 4.75-kHz sinusoidal suppressor gated with the 4-kHz
      masker, for suppressor levels of 40-70 dB SPL. The decrease in gain (increase in
      suppression) as a function of suppressor level was greater with a 3-kHz
      suppressor than with a 4.75-kHz suppressor, in line with previous findings.
      Basilar membrane input-output (I/O) functions derived from the TMCs showed a
      shift to higher input (4-kHz masker) levels of the low-level (linear) portion of
      the I/O function with the addition of a suppressor, with partial linearization of
      the function, but no reduction in maximum compression.

PMID- 17550183
TI  - Auditory short-term memory persistence for tonal signals in a songbird.
AB  - This paper presents an animal model for studying the persistence of auditory
      memory for tonal signals. Five European starlings (Sturnus vulgaris) were trained
      in a Go/NoGo delayed nonmatching-to-sample task to discriminate between a series
      of identical "sample stimuli" and a single "test stimulus." Frequencies of sample
      and test stimuli should be classified as being either the same or different. The
      performance of the birds is measured as the percentage of correct
      classifications. Three parameters were varied: The delay between sample and test
      stimuli, the number of sample stimuli presented before the test stimulus, and the
      salience of the difference between sample and test stimuli. Auditory memory
      persistence time was estimated as a function of the delay between the last sample
      stimulus and the test stimulus. The performance of the birds deteriorated with
      increasing delay before the test stimulus. Increasing the number of sample
      stimuli in the series of tones presented before the test stimulus improved
      performance. Performance was also better for more salient differences between
      sample and test stimuli. The individual auditory memory persistence time varied
      between 4 and 20 s.

PMID- 17550184
TI  - Directional loudness and binaural summation for wideband and reverberant sounds.
AB  - In an earlier investigation [Sivonen and Ellermeier, J. Acoust. Soc. Am. 119,
      2965-2980 (2006)], the effect of sound incidence angle on loudness was
      investigated for anechoic, narrowband sounds. In the present follow-up
      investigation, the effect of incidence angle on loudness was investigated using
      wideband sounds under anechoic conditions and narrowband sounds under reverberant
      conditions. Five listeners matched the loudness of a sound coming from five
      incidence angles in the horizontal plane to that of the same sound with frontal
      incidence. These directional loudness matches were obtained with an adaptive, two
      alternative, two-interval, forced-choice procedure. The stimuli were presented to
      the listeners via individual binaural synthesis. The results show that loudness
      depends on sound incidence angle in both experiments. The wideband and
      reverberant sounds, however, yielded significantly smaller directional effects
      than had been obtained for the same listeners when anechoic, narrowband sounds
      were used. When modeling the binaural summation underlying the loudness matches,
      a power summation of the at-ear signals yielded good predictions for all types of
      stimuli investigated.

PMID- 17550185
TI  - Effects of simultaneous perturbations of voice pitch and loudness feedback on
      voice F0 and amplitude control.
AB  - Perturbations in either voice pitch or loudness feedback lead to changes in a
      speaker's voice fundamental frequency (F0) or amplitude. Voice pitch or loudness
      perturbations were presented individually (either pitch or loudness shift
      stimuli) or simultaneously (pitch combined with loudness shift stimuli) to
      subjects sustaining a vowel to test the hypothesis that the mechanisms for these
      two response types are independent. For simultaneous perturbations, pitch and
      loudness both changed in the same direction or in opposite directions. Results
      showed that subjects responded with voice F0 or amplitude responses that opposed
      the direction of the respective pitch- or loudness shift stimuli. Thus, depending
      on the stimulus direction, both responses could either change in the same
      direction or in the opposite direction to each other. F0 response magnitudes were
      greatest with pitch-shift only stimuli (18 cents), smallest for loudness shift
      stimuli (10 cents) and intermediate with pitch combined with loudness shift
      stimuli (13 and 16 cents). Amplitude responses were largest with +3 dB stimuli
      (0.96 dB) and smallest with -3 dB stimuli (0.49 dB) but were not affected by the
      addition of pitch-shift stimuli. Results suggest the F0 and amplitude response
      mechanisms may be independent but interact in some conditions.

PMID- 17550186
TI  - The minimum glottal airflow to initiate vocal fold oscillation.
AB  - Phonation threshold flow (PTF) is proposed as a new aerodynamic parameter of the
      speech production system in this study. PTF is defined as the minimum airflow
      that can initiate stable vocal fold vibration. Because the glottal airflow can be
      noninvasively measured, it is suggested that the aerodynamic parameter PTF may be
      more practical for clinical vocal disease assessment. In order to investigate the
      relationship between PTF and phonatory system properties, the stability of the
      body-cover vocal fold model was analyzed. The study has theoretically shown that
      PTF is a sensitive aerodynamic parameter dependent on tissue properties, glottal
      configuration, and vocal tract loading. It was predicted that PTF can be reduced
      by decreasing tissue viscosity, decreasing mucosal wave velocity, increasing
      vocal fold thickness, or decreasing prephonatory glottal area. Furthermore, it
      was predicted that a divergent glottis or low vocal tract resistance lead to a
      reduced PTF. Also discussed is the potential significance of PTF in investigating
      the energy distribution in a vocal fold vibration system and related clinical
      applications.

PMID- 17550187
TI  - Perceptual rate normalization in naturally produced rate-varied speech.
AB  - The perception of voicing categories is affected by speaking rate, so that
      listeners' category boundaries on a VOT continuum shift to a lower value when
      syllable duration decreases [Miller and Volaitis, Percept. Psychophys. 46, 505
      512 (1989); Volaitis and Miller, J. Acoust. Soc. Am. 92, 723-735 (1992)].
      Previous rate normalization effects have been found using artificially varied
      stimuli. This study examines the effect of speech rate on voicing categorization
      in naturally produced rate-varied speech. The stimuli contained natural decreases
      in VOT with faster speech rates so that VOT values for /b/ and /p/ overlapped at
      the fastest rates. Consonant identification results showed that the rate effects
      on the perceptual boundary between /p/ and /b/ very closely matched the effects
      of rate on the productions, though there was a small mismatch with fast rate
      productions whereby voiced stops were systematically miscategorized as voiceless.
      Another group of listeners judged the goodness of the consonant, indicating that
      best exemplars were rate-varied and shifted away from the /p/-/b/ boundary. These
      results are discussed in light of exemplar-based and abstractionist models of
      speech perception.

PMID- 17550188
TI  - Dental-to-velar perceptual assimilation: a cross-linguistic study of the
      perception of dental stop+/l/ clusters.
AB  - French listeners perceive illegal /tl/ and /dl/ clusters as legal /kl/ and /gl/,
      suggesting that /dl, tl/ undergo "phonotactic perceptual assimilation" to the
      phonetically most similar permissible clusters [Halle et al., J. Exp. Psychol.
      Hum. Percept. Perform. (1998)]. However, without a comparison to native speakers
      of a language allowing initial /tl, dl/, other explanations remain open (e.g.,
      universal phonetic biases). Experiment 1 compared native French and Hebrew
      listeners on perception of Hebrew /tl/-/kl/ and /dl/-/gl/. On a language-specific
      phonotactics account, these contrasts should be difficult for listeners whose
      language disallows initial /tl, dl/ while allowing /kl, gl/ (French), but not for
      listeners whose language permits all four clusters (Hebrew). Indeed, French but
      not Hebrew listeners showed difficulty discriminating /tl/-/kl/, and tended to
      categorize the initial consonant of /tl/ as /k/; analogous effects for /dl/-/gl/
      were weaker. Experiment 2 tested speakers of American English, which also
      disallows initial /tl, dl/ but realizes stop-voicing differently than French or
      Hebrew, to examine possible contributions of language-specific phonetic settings.
      Their performance was similar to that of French listeners, though they had
      significantly greater difficulty with /dl-/gl/. The results support the proposal
      of language-specific phonotactic perceptual assimilation, with modest
      contributions from language-specific phonetic settings.

PMID- 17550189
TI  - Effects of aging on word intelligibility and listening difficulty in various
      reverberant fields.
AB  - Listening difficulty ratings is a new measure to evaluate speech transmission
      performance in public spaces. The advantage is that it can evaluate sound fields
      with higher speech transmission performance more accurately and sensitively than
      intelligibility scores. The effect of aging, or hearing level on listening
      difficulty ratings has not been clarified yet. In this paper, the results of the
      listening tests demonstrated that hearing levels above 2 kHz significantly affect
      both word intelligibility scores and listening difficulty ratings for the aged.
      For the aged, both of them can be estimated from the results for the young plus
      the average of hearing levels at 2 and 4 kHz. The equations for estimating the
      word intelligibility scores and the listening difficulty ratings for the aged are
      obtained from the multiple linear regression analyses. The estimated scores and
      ratings generally coincide with the measured scores and ratings, and the averaged
      difference between them is 5.2% for the word intelligibility scores and 3.8% for
      the listening difficulty ratings, in the range of listening tests performed in
      this paper.

PMID- 17550190
TI  - Effectiveness of computer-based auditory training in improving the perception of
      noise-vocoded speech.
AB  - Five experiments were designed to evaluate the effectiveness of "high
      variability" lexical training in improving the ability of normal-hearing subjects
      to perceive noise-vocoded speech that had been spectrally shifted to simulate
      tonotopic misalignment. Two approaches to training were implemented. One training
      approach required subjects to recognize isolated words, while the other training
      approach required subjects to recognize words in sentences. Both approaches to
      training improved the ability to identify words in sentences. Improvements
      following a single session (lasting 1-2 h) of auditory training ranged between 7
      and 12 %pts and were significantly larger than improvements following a visual
      control task that was matched with the auditory training task in terms of the
      response demands. An additional three sessions of word- and sentence-based
      training led to further improvements, with the average overall improvement
      ranging from 13 to 18% pts. When a tonotopic misalignment of 3 mm rather than 6
      mm was simulated, training with several talkers led to greater generalization to
      new talkers than training with a single talker. The results confirm that computer
      based lexical training can help overcome the effects of spectral distortions in
      speech, and they suggest that training materials are most effective when several
      talkers are included.

PMID- 17550191
TI  - Tone recognition in continuous Cantonese speech using supratone models.
AB  - This paper studies automatic tone recognition in continuous Cantonese speech.
      Cantonese is a major Chinese dialect that is known for being rich in tones. Tone
      information serves as a useful knowledge source for automatic speech recognition
      of Cantonese. Cantonese tone recognition is difficult because the tones have
      similar shapes of pitch contours. The tones are differentiated mainly by their
      relative pitch heights. In natural speech, the pitch level of a tone may shift up
      and down and the F0 ranges of different tones overlap with each other, making
      them acoustically indistinguishable within the domain of a syllable. Our study
      shows that the relative pitch heights are largely preserved between neighboring
      tones. A novel method of supratone modeling is proposed for Cantonese tone
      recognition. Each supratone model characterizes the F0 contour of two or three
      tones in succession. The tone sequence of a continuous utterance is formed as an
      overlapped concatenation of supratone units. The most likely tone sequence is
      determined under phonological constraints on syllable-tone combinations. The
      proposed method attains an accuracy of 74.68% in speaker-independent tone
      recognition experiments. In particular, the confusion among the tones with
      similar contour shapes is greatly resolved.

PMID- 17550192
TI  - Statistical voice activity detection based on integrated bispectrum likelihood
      ratio tests for robust speech recognition.
AB  - Currently, there are technology barriers inhibiting speech processing systems
      that work in extremely noisy conditions from meeting the demands of modern
      applications. These systems often require a noise reduction system working in
      combination with a precise voice activity detector (VAD). This paper shows
      statistical likelihood ratio tests formulated in terms of the integrated
      bispectrum of the noisy signal. The integrated bispectrum is defined as a cross
      spectrum between the signal and its square, and therefore a function of a single
      frequency variable. It inherits the ability of higher order statistics to detect
      signals in noise with many other additional advantages: (i) Its computation as a
      cross spectrum leads to significant computational savings, and (ii) the variance
      of the estimator is of the same order as that of the power spectrum estimator.
      The proposed approach incorporates contextual information to the decision rule, a
      strategy that has reported significant benefits for robust speech recognition
      applications. The proposed VAD is compared to the G.729, adaptive multirate, and
      advanced front-end standards as well as recently reported algorithms showing a
      sustained advantage in speech/nonspeech detection accuracy and speech recognition
      performance.

PMID- 17550193
TI  - Loudness control in pianists as exemplified in keystroke force measurements on
      different touches.
AB  - The relationship between the key depression force on an upright piano and the
      level of loudness of a generated tone was examined when pianists hit a force
      sensor built-in key with "struck" or "pressed" type of touch. The vertical
      displacement of the key, and the radiated piano sounds were also recorded. It was
      found that for both types of touch, simple exponential functions could adequately
      describe the relation of the force amplitude with the level of the piano tone as
      well as that of the impulse of the force with the piano tone. The impulse of the
      force generated before the maximum key depression moment commonly amounted to
      above 80% of the total impulse produced at the tone below mezzo-forte. It,
      however, decreased to around 60% at fortissimo, indicating a decrease in the
      efficiency of the force application for sound production. The two types of touch
      differed in their force profiles. The struck touch was characterized by a steeper
      initial force increase with greater fluctuations in the subsequent period than
      the pressed touch. The struck touch also demonstrated lower maximum force and
      less impulse at fortissimo. The inter-pianist variation in the force and impulse,
      and the "finger-noise" are also herein examined.

PMID- 17550194
TI  - Vibrotactile transduction and transducers.
AB  - The body's sense of touch is potentially a versatile channel for the conveyance
      of directional, spatial, command, and timing information. Most practical
      implementations of vibrotactile systems require compact, light-weight actuators
      that can be mounted against the body. Eccentric mass motors are widely used for
      this application, yet their output is limited and the effects of loading on the
      transducers due to the skin and mounting arrangement have been largely ignored.
      Conventional linear actuators are well suited as vibrotactile transducers and can
      provide high output, but are typically limited to laboratory research due to
      their large size and cost. The effect of loading on various practical
      vibrotactile transducers is investigated using a skin impedance phantom and
      measuring the transducer displacement with respect to additional mass loading.
      Depending on the transducer design, loading can dramatically reduce the vibratory
      displacement and, in the case of eccentric mass motors, also increase the
      operating frequency. In contrast, a new linear actuator design can be designed to
      be almost independent of skin loading, by considering the mechanical impedance of
      the load and optimizing the transducer contact area.

PMID- 17550195
TI  - Characteristics of whistles from resident bottlenose dolphins (Tursiops
      truncatus) in southern Brazil.
AB  - Little is known of the whistles produced by bottlenose dolphins in the South
      Atlantic Ocean. A total of 788 whistles were recorded from free-ranging
      bottlenose dolphins in Patos Lagoon estuary, southern Brazil. The mean number of
      whistles emitted per minute per animal was 0.8. Bottlenose dolphins emitted a
      varied repertoire of whistles, in which those with more than one inflection point
      were the most frequent and there was no predominance of ascending or descending
      whistles. Whistles recorded had a great frequency range, between 1.2 and 22.3
      kHz. Whistle duration was 553.3 (+/- 393.9 ms) and 66.6% of the whistles lasted <
      800 ms. Differences in the mean values of the whistles' characters were found
      between this study and other values previously reported for Tursiops. Bottlenose
      dolphins in the Patos Lagoon estuary emitted repeated whistle contours and
      individuals may be sharing some whistle types, as it has been suggested for
      Tursiops.

PMID- 17550196
TI  - Acoustic signals of Chinese alligators (Alligator sinensis): social
      communication.
AB  - This paper reports the first systematic study of acoustic signals during social
      interactions of the Chinese alligator (Alligator sinensis). Sound pressure level
      (SPL) measurements revealed that Chinese alligators have an elaborate acoustic
      communication system with both long-distance signal-bellowing-and short-distance
      signals that include tooting, bubble blowing, hissing, mooing, head slapping and
      whining. Bellows have high SPL and appear to play an important role in the
      alligator's long range intercommunion. Sounds characterized by low SPL are short
      distance signals used when alligators are in close spatial proximity to one
      another. The signal spectrographic analysis showed that the acoustic signals of
      Chinese alligators have a very low dominant frequency, less than 500 Hz. These
      frequencies are consistent with adaptation to a habitat with high density
      vegetation. Low dominant frequency sound attenuates less and could therefore
      cover a larger spatial range by diffraction in a densely vegetated environment
      relative to a higher dominant frequency sound.

PMID- 17550197
TI  - The allocation of energy to echolocation pulses produced by soprano pipistrelles
      (Pipistrellus pygmaeus) during the wingbeat cycle.
AB  - Soprano pipistrelles exhibit considerable plasticity in both the structure and
      rate of echolocation call production. In search phase in the laboratory, calls
      are produced either as a single pulse per wingbeat cycle, or as double pulses.
      The amplitude of double pulses is reduced compared to the preceding single pulse.
      The energy flux density of either pulse of a double pulse per wingbeat was lower
      than a single pulse per wingbeat, and is achieved by a combination of reduction
      in both duration and amplitude. The combined energy of the double pulses is not
      significantly greater than the single pulse which precedes it. The decision to
      produce a double pulse may be an indication of the bat requiring additional
      information from the target. The production of double pulses per wingbeat may
      serve to achieve a higher rate of information flow for no significant increase in
      energetic expenditure when a possible target is detected. The proposal that
      echolocation during flight comes for free as a by-product of the intimate
      coupling among wingbeat, respiration, and echolocation is discussed.

PMID- 17550198
TI  - Biosonar signals impinging on the target during interception by big brown bats,
      Eptesicus fuscus.
AB  - Big brown bats (Eptesicus fuscus) were videotaped in the dark with a night-vision
      lens and infrared illumination while flying repeatedly along the same straight
      course to seize a tethered mealworm or a small electret microphone used to record
      biosonar signals impinging on the target. Bats emitted frequency-modulated sounds
      with first to third harmonics covering frequencies from 23 to 105 kHz. As the
      bats neared the target, the first harmonic shifted lower in frequency while the
      third harmonic strengthened and the fourth harmonic, and sometimes the fifth
      harmonic, appeared. Incident-sound bandwidth remained broad throughout the
      maneuver, a feature not seen in field recordings of rapidly moving bats due to
      propagation losses and uncontrolled directional effects. Sound pressures at the
      microphone increased by about 20 dB during approach from 2.5 m down to 50 cm and
      then leveled off, indicating that emitted amplitudes were approximately constant
      until the terminal stage, when they progressively decreased for the remainder of
      the maneuver. Interpulse intervals decreased from 80-100 ms down to about 6-7 ms
      and then stabilized throughout the terminal stage, while durations decreased
      smoothly from 3-4 ms (limited by adjacent wall) down to 0.5 ms during the
      terminal stage, which ended with capture.

PMID- 17550199
TI  - Noise level correlates with manatee use of foraging habitats.
AB  - The introduction of anthropogenic sound to coastal waters is a negative side
      effect of population growth. As noise from boats, marine construction, and
      coastal dredging increases, environmental and behavioral monitoring is needed to
      directly assess the effect these phenomena have on marine animals. Acoustic
      recordings, providing information on ambient noise levels and transient noise
      sources, were made in two manatee habitats: grassbeds and dredged habitats.
      Recordings were made over two 6-month periods from April to September in 2003 and
      2004. Noise levels were calculated in one-third octave bands at nine center
      frequencies ranging from 250 Hz to 64 kHz. Manatee habitat usage, as a function
      of noise level, was examined during four time periods: morning, noon, afternoon,
      and night. Analysis of sightings data in a variety of grassbeds of equal species
      composition and density indicate that manatees select grassbeds with lower
      ambient noise for frequencies below 1 kHz. Additionally, grassbed usage was
      negatively correlated with concentrated boat presence in the morning hours; no
      correlation was observed during noon and afternoon hours. This suggests that
      morning boat presence and its associated noise may affect the use of foraging
      habitat on a daily time scale.

PMID- 17550200
TI  - Characterization of uncertainty in outdoor sound propagation predictions.
AB  - Predictive skill for outdoor sound propagation is assessed using high-resolution
      atmospheric fields from large-eddy simulations (LES). Propagation calculations
      through the full LES fields are compared to calculations through subsets of the
      LES fields that have been processed in typical ways, such as mean vertical
      profiles and instantaneous vertical profiles synchronized to the sound
      propagation. It is found that mean sound pressure levels can be predicted with
      low errors from the mean profiles, except in refractive shadow regions.
      Prediction of sound pressure levels for short-duration events is much less
      accurate, with errors of 8 -10 dB for near-ground propagation being typical.

PMID- 17550201
TI  - Fast automatic inharmonicity estimation algorithm.
AB  - A new algorithm is presented for estimating the inharmonicity coefficient of
      slightly inharmonic stringed instrument sounds. In the proposed partial
      frequencies deviation method, the inharmonicity is estimated in an intuitive way
      by minimizing the deviation of the expected partial frequencies compared to the
      frequencies of the high amplitude peaks in the spectrum. This is done in an
      iterative process, where the algorithm converges towards the target estimation
      value. The algorithm is tested using both synthetic and recorded piano tones. The
      results show that the new algorithm produces accurate results with a small
      computation cost compared to other methods.

PMID- 17550202
TI  - Simulating the acquisition of lexical tones from continuous dynamic input.
AB  - Infants develop phonetic categories by simply being exposed to adult speech. It
      remains unclear, however, how they handle the extensive variability inherent to
      speech, and how they process multiple linguistic functions that share the same
      acoustic parameters. Across four neural network simulations of lexical tone
      acquisition, self-organizing maps were trained with continuous speech input of
      increasing variability. Robust tonal categorization was achieved by tracking the
      velocity profiles of fundamental frequency contours. This result suggests that
      continuous speech signal carries sufficient categorical information that can be
      directly processed, and that dynamic acoustic information can be used for
      resolving the variability problem.

PMID- 17550203
TI  - Effects of auditory feedback deprivation length on the vowel /epsilon/ produced
      by pediatric cochlear-implant users.
AB  - Effects of auditory deprivation on speech production by ten cochlear-implanted
      children were investigated by turning off the implant for durations ranging from
      0.3 to 5.0 s and measuring the formant frequencies (F1 and F2) of the vowel
      /epsilon/. In five of the ten talkers, F1 and/or F2 shifted when auditory
      feedback was eliminated. Without feedback, F2 frequency lowered consistently,
      suggesting vowel centralization. Phonetic transcription indicated that some of
      these acoustic changes led to perceptible shifts in phonetic quality. The results
      provide evidence that brief periods of auditory deprivation can produce
      perceptible changes in vowels produced by some cochlear-implanted children.

PMID- 17550204
TI  - An exact point source starting field for the Fourier parabolic equation in
      outdoor sound propagation.
AB  - A method for exactly representing a point source starting field in a Fourier
      parabolic equation calculation is presented. The formulation is based on an
      exact, analytic expression for the field in vertical wave number space (k space).
      The field in vertical coordinate space (z space) is obtained via a Fourier
      transform of the k-space field. Thus, one can directly control the Fourier
      components of the starting field, so that nonpropagating components are excluded.
      The relation of the exact starting field to the standard Gaussian starting field
      is demonstrated analytically. Examples of the numerical implementation of the
      exact starting field are given.

PMID- 17550205
TI  - Destabilization of velocity feedback controllers with stroke limited inertial
      actuators.
AB  - It has been observed when using inertial actuators for the active reduction of
      structural vibration, that velocity feedback controllers are liable to become
      unstable if the actuator is subject to stroke saturation. This article presents a
      simple nonlinear, time domain model of an inertial actuator mounted on a single
      degree of freedom system. At low amplitudes the actuator, when used in a velocity
      feedback control loop, increases the effective damping of the structure. At
      higher amplitudes the system is shown to become unstable, however, and generates
      limit cycle oscillations having a predictable frequency.

PMID- 17550206
TI  - Nonlinear frequency-dependent attenuation in sandy sediments.
AB  - This paper summarizes evidence of a nonlinear frequency dependence of attenuation
      for compressional waves in shallow-water waveguides with sandy sediment bottoms.
      Sediment attenuation is found consistent with alpha(f) = alpha(f(o)) x (f/f(o))n,
      n approximately 1.8 +/- 0.2 at frequencies less than 1 kHz in agreement with the
      theoretical expectation, (n = 2), of Biot [J. Acoust. Soc. Am. 28(2), 168-178,
      1956]. For frequencies less than 10 kHz, the sediment layers, within meters of
      the water-sediment interface, appear to play a role in the attenuation that
      strongly depends on the power law. The accurate calculation of sound transmission
      in a shallow-water waveguide requires the depth-dependent sound speed, density,
      and frequency-dependent attenuation.

PMID- 17550207
TI  - "The Newborn Screening Saves Lives Act"--four million calls for support!

PMID- 17550208
TI  - The management of central diabetes insipidus in infancy: desmopressin, low renal
      solute load formula, thiazide diuretics.
AB  - Infants consume most of their calories as formula. Because of this large fluid
      intake, infants normally produce dilute urine, not far off from that seen in
      individuals with diabetes insipidus (DI). Infants with DI are therefore prone to
      water intoxication if fixed antidiuresis is achieved using the long-acting
      vasopressin analog desmopressin (DDAVP), which induces a state of high urine
      concentration. DI treatment approaches applied to older children and adults, who
      consume the their calories as solids, are difficult to apply to infants with DI.
      When used in infants, oral and intranasal DDAVP can be associated with wide
      swings in serum sodium concentration (SNA). In comparison, precisely administered
      subcutaneous doses of DDAVP can be successfully used in infants with DI, and
      appear to be superior to oral or intranasal DDAVP therapy. Alternatively,
      consistent eunatremia can be simply achieved in infantile DI using low renal
      solute load (RSL) formula and thiazide diuretics. Low RSL formula reduces
      obligatory urinary water losses, and thiazide diuretics concentrate the urine to
      levels seen in normal formula-fed infants. This report addresses treatment
      options of DI in infancy and the delicate management issues involved.

PMID- 17550209
TI  - Three faces of hypothalamic tumors.

PMID- 17550210
TI  - Hirsutism in adolescent girls.

PMID- 17550211
TI  - Functional ovarian hyperandrogenism and polycystic ovary syndrome in prepubertal
      girls with obesity and/or premature pubarche.
AB  - AIMS: Functional ovarian hyperandrogenism (FOH) is considered to be a form of
      polycystic ovary syndrome (PCOS) at adolescence. There are almost no data in the
      prepubertal period, although one of the earliest manifestations of PCOS is
      premature pubarche. Prepubertal girls with obesity or insulin resistance are also
      at risk to develop the full PCOS phenotype after puberty. The aim of this study
      was to evaluate prepubertal girls with premature pubarche and/or obesity for PCOS
      or FOH. METHODS: Twenty-seven prepubertal girls with premature pubarche and/or
      obesity aged >6 years were evaluated. FOH was defined as abnormal ovarian 17OHP
      response to challenge with GnRH analog of >2 ng/ml after exclusion of adrenal
      dysfunction. All patients underwent a pelvic ultrasound examination. RESULTS:
      Sixteen patients had premature pubarche, seven were obese, and four had both
      premature pubarche and obesity. Eleven of 27 patients (40.7%) showed high (>2
      ng/ml) 17OHP response to GnRH challenge. Three patients (11%) with FOH also
      showed PCO morphology on pelvic ultrasound examination. CONCLUSION: In
      prepubertal girls who carry risk factors, including genetic polymorphisms and/or
      particular environmental factors, FOH/PCOS could develop at a high rate.

PMID- 17550212
TI  - Correlation between AVPR2 mutations and urinary AQP2 excretion in patients with
      nephrogenic diabetes insipidus.
AB  - Activation of the V2 receptor by arginine vasopressin (AVP) results in
      trafficking of the water channel AQP2 to the luminal plasma membrane and a small
      amount into the urine. Mutations in the A VPR2 gene, encoding the AVP V2
      receptor, result in congenital nephrogenic diabetes insipidus (CNDI). To
      determine a correlation between A VPR2 mutations and urinary AQP2 excretion,
      immunobloting was used to detect AQP2 in the urine of patients with CNDI before
      and after a dehydration test. The patients' genotype was determined using PCR
      amplification and direct sequencing of the complete A VPR2 gene. Urinary AQP2
      excretion was absent in patients with severely debilitating mutations, a novel
      total deletion of the A VPR2 gene, and a novel nonsense mutation W296X. However,
      it was detected in siblings with a V88M missense mutation. Urinary AQP2 excretion
      correlated well with other tested phenotype markers. Urinary AQP2 excretion could
      be used to evaluate the remaining in vivo integrity of the AVP-V2 receptor-AQP2
      cascade in patients with CNDI.

PMID- 17550213
TI  - Nutrient intake and body composition variables in Prader-Willi syndrome--effect
      of growth hormone supplementation and genetic subtype.
AB  - In patients with Prader-Willi syndrome (PWS), limited information exists on the
      effects of growth hormone (GH) therapy, gender and genetic subtype on nutrient
      intake and body composition. We therefore compared GH-treated and nontreated
      patients, taking into account Tanner stage, gender, and genetic form. PATIENTS
      AND METHODS: In 37 individuals with PWS (20/17 M/F; 21/16 GH+/GH-), dietary
      intake and body composition (BMI, DEXA) were assessed. RESULTS: Older GH-treated
      children (Tanner stage 3-4) displayed improved body composition variables (BMI,
      total and percentage fat mass, truncal fat) (p < 0.05), despite dietary intake
      similar to non-treated patients; younger children (Tanner stage 1-2) displayed a
      different pattern, despite greater total caloric and fat intake (p < 0.05) with
      GH treatment, with only minor differences in body composition. Genetic form and
      gender had no intrinsic effect on nutrient intake or body composition.
      CONCLUSION: In 37 patients with PWS, GH treatment selectively affected body
      composition (BMI, fat mass), and dietary fat intake based on patients'
      developmental status, while these variables were unaffected by gender or genetic
      subtype.

PMID- 17550214
TI  - Late rise of thyroid stimulating hormone in ill newborns.
AB  - OBJECTIVES: To determine the frequency and characteristics of late rise of
      thyroid stimulating hormone (LRT) among ill newborns. INFANTS AND METHODS: Data
      were retrospectively analyzed from infants in intensive care settings with
      abnormal thyroid tests over 13 months. Thyroid tests were performed by filter
      paper if neonatal intensive care >4 weeks or serum if clinically indicated. LRT
      was defined as thyroid stimulating hormone (TSH) >10 microIU/ml after normal TSH
      on initial newborn screen. RESULTS: LRT was identified in 13 infants. Of 736
      admissions to the neonatal intensive care unit (NICU), 10 (1.4%) had LRT.
      Excluding 3/10 with diagnosis at <1 week of age the frequency is 0.95%. Three
      additional cases occurred in other ICUs. TSH elevation resolved in 6/13 (group A,
      TSH 10.6-20.6 microIU/ml) and persisted in 7/13 necessitating treatment (group B,
      TSH 10.5-1326 microIU/ml). 7/13 had birth weights <1500 g. 11/13 had gestational
      ages <37 weeks. LRT was associated with surgery, sepsis workup, dopamine, and
      gastrointestinal disorders. CONCLUSIONS: LRT was not infrequent in ill newborns.
      Most were premature and half were not very low birth weight. We recommend
      monitoring of thyroid function by serum specimen in ill newborns with prolonged
      ICU care regardless of birth weight.

PMID- 17550215
TI  - Changes in thyroid morphology and function in children in western Poland as a
      result of intensified iodine prophylaxis.
AB  - AIM: To determine the changes in thyroid pathology resulting from obligatory salt
      iodization in a group of children aged 8-12 years from the rural and urban areas
      of Wielkopolska Region, Poland. POPULATION AND METHODS: The survey was conducted
      on 1215 children, of both sexes, 402 of whom were examined in 1992 (before salt
      iodization), 408 in 2000, and 405 in 2005 (after salt iodization beginning in
      1996). Thyroid ultrasound, urinary iodine, FT4, FT3, TSH and antithyroid
      antibodies were measured. RESULTS: A significant drop in goiter cases was
      observed (35.4% in 1992 vs 6.3% in 2005), coupled with a marked increase of
      urinary iodine. There were also changes in ultrasonography and elevated levels of
      antibodies. CONCLUSIONS: The study proves the high efficacy of iodine
      prophylaxis. Despite a growing number of children with elevated antithyroid
      antibody titers, only a slight increase of autoimmune thyroid disorders was
      observed.

PMID- 17550216
TI  - Glycaemic control and hypoglycaemia in children, adolescents and young adults
      with unstable type 1 diabetes mellitus treated with insulin glargine or
      intermediate-acting insulin.
AB  - In this open study of clinical practice, 142 paediatric patients with type 1
      diabetes mellitus (>1 year duration), stratified by age, received prandial
      insulin (regular or lispro) and either once daily insulin glargine (GLAR; n=74),
      titrated to target fasting blood glucose (FBG) levels 4.4-7.8 mmol/l, or
      NPH/semilente insulin (NPH insulin, administered once, twice or three times
      daily; n=68), titrated to target FBG 4.4-8.9 mmol/l. Both groups were treated for
      20 +/- 10 months. HbA(1c) significantly increased in GLAR (7.3 +/- 1.0% to 7.6 +/
      1.1%; p = 0.003) and NPH/semilente insulin (7.7 +/- 1.6% to 8.3 +/- 1.5%; p =
      0.0001) treated patients. The incidence of symptomatic hypoglycaemia was
      comparable between GLAR versus NPH/semilente insulin at endpoint (2.19 vs. 1.94
      episodes/week); however, the overall incidence of severe hypoglycaemia was
      significantly lower with GLAR versus NPH/semilente insulin (0.14 vs. 0.73
      events/patient-year; p = 0.002). The daily insulin dose was similar between the
      treatment groups; however, perceived quality of life (QoL) was better with GLAR.
      GLAR is associated with equivalent glycaemic control, less severe hypoglycaemia
      and improved QoL compared with NPH/semilente insulin.

PMID- 17550217
TI  - Stressful life events and psychological dysfunctions before the onset of type 1
      diabetes mellitus.
AB  - AIM: To test the hypothesis that stressful life events and psychological
      dysfunction increase the risk for development of type 1 diabetes mellitus (DM1).
      METHOD: A case-control study comprising 105 children with DM1 and 210 controls
      matched by age +/- 1 year), sex and place of residence. Conditional univariate
      and multivariate logistic regressions were used to analyze the data. RESULTS:
      After adjustment for possible confounders, the following factors were positively
      related to DM1: parents' job-related issues changed or lost job (odds ratio [OR]
      11.5, 95% confidence interval [CI] 1.6-81.8); other severe life events--severe
      accident, hospitalization or death of close friend, quarrels between parents, war
      in republics of former Yugoslavia, near-drowning in a pool, falling down, unhurt
      participant of an accident (OR 68.5, 95% CI 13.5-349.0); other minor life events-
      conflicts with parents/teacher/neighbors, lost in town, physical attack, failure
      in competition, penalty, examination, death of pet, presence at lightning strike,
      thrown out of dwelling (OR 32.7, 95% CI 6.3-169.6); and learning problems (OR
      17.5, 95% CI 4.3-71.6). CONCLUSION: These results support the hypothesis that
      stressful life events and psychological dysfunctions are associated with DM1.

PMID- 17550218
TI  - Neonatal hyperthyroidism: neonatal clinical course of two brothers born to a
      mother with Graves-Basedow disease, before and after total thyroidectomy.
AB  - BACKGROUND: About 1-2% of infants born to mothers with Graves' disease or
      Hashimoto's thyroiditis develop neonatal hyperthyroidism because of
      transplacental passage of IgG stimulating TSH receptors (TRAb). OBJECTIVE: To
      evaluate the effect of maternal total thyroidectomy on neonatal clinical course.
      METHODS: We describe two brothers born to a mother with Graves' disease, before
      and after total thyroidectomy. RESULTS: The first child showed persistent
      tachycardia, the presence of TRAb and a laboratory pattern of hyperthyroidism.
      Lugol's solution was started and then propylthiouracil was added. Digitalis,
      furosemide and diazepam were necessary for treatment of heart failure,
      hypertension and irritability. On the 70th day of life, hormone serum levels
      normalized and treatment was interrupted. TRAb normalized by the third month of
      life. The second infant was born 2 years after the mother underwent total
      thyroidectomy. In spite of a laboratory pattern of hyperthyroidism and positivity
      to TRAb, he showed only considerable weight loss, and no therapy was required.
      CONCLUSIONS: TRAb may persist after total thyroidectomy: clinical and
      instrumental follow-up of the newborn is recommended.

PMID- 17550219
TI  - Development of diabetes mellitus in two boys after the initiation of growth
      hormone therapy.
AB  - In addition to its growth promoting properties, growth hormone (GH) has anti
      insulin effects that could cause hyperglycemia. Development of diabetes mellitus
      as a result of GH therapy has been an ever-present, albeit rarely reported,
      concern. This report is that of two adolescent boys who developed diabetes
      mellitus after the initiation of treatment with GH.

PMID- 17550220
TI  - Orthotopic liver transplantation in glucose-6-phosphatase deficiency--Von Gierke
      disease--with multiple hepatic adenomas and concomitant focal nodular
      hyperplasia.
AB  - Von Gierke disease is occasionally complicated by hepatic adenomas (HAs) causing
      great concern owing to the current difficulties in monitoring them regarding
      malignant transformation. Orthotopic liver transplantation (OLT) is proposed as a
      therapeutic tool when multiple HAs and poor metabolic control are present, owing
      to the lack of a clear-cut criterion to detect early malignant transformation,
      whether or not associated with growth retardation. Focal nodular hyperplasia
      (FNH) has never been described together with multiple adenomas in von Gierke
      disease. We report a 26-year-old woman with von Gierke disease complicated by
      multiple HAs concomitant with FNH who underwent OLT and is now free from disease
      symptoms with good long-term outcome. In conclusion, although FNH could have been
      managed clinically, when multiple adenomas are present, OLT should be planned for
      some patients, mainly for those with poor metabolic control.

PMID- 17550221
TI  - Re: Editorial: It is (sort of) a boy and (sort of) a girl. You have (sort of) a
      say and you (sort of) don't? The uneasiness of genital restoration surgery [JPEM
      2006(11); 19: 1285-1289].

PMID- 17550222
TI  - Managing variation in sex development.

PMID- 17550223
TI  - Managing variation in sex development.

PMID- 17550224
TI  - Solvent-mediated proton transfer in catalysis by carbonic anhydrase.
AB  - Considerable attention has been focused on proton transfer through intervening
      water molecules in complex macromolecules of biological interest, such as
      bacteriorhodopsin, cytochrome c oxidase, and many others. Proton transfer in
      catalysis by carbonic anhydrase provides a useful model for the study of the
      properties of such proton translocations. High-resolution X-ray crystallography
      in combination with measurements of catalysis have revealed new details of this
      process. A prominent proton shuttle residue His64 shows evidence of structural
      mobility, which appears to enhance proton transfer between the active site and
      bulk solvent. Moreover, the properties of the imidazole side chain of His64,
      including its conformations and pK(a), are finely tuned by surrounding residues
      of the active-site cavity. The structure of a network of ordered solvent
      molecules located between His64 and the active site are also sensitive to
      surrounding residues. These features combine to provide efficient proton-transfer
      rates as great as 10(6) s(-1) necessary to sustain rapid catalysis.

PMID- 17550225
TI  - Heme-copper/dioxygen adduct formation, properties, and reactivity.
AB  - This Account focuses on our recent developments in synthetic heme/copper/O 2
      chemistry, potentially relevant to the mechanism of action of heme-copper
      oxidases (e.g., cytochrome c oxidase) and to dioxygen activation chemistry.
      Methods for the generation of O 2 adducts, which are high-spin heme(Fe (III))
      peroxo-Cu (II) complexes, are described, along with a detailed
      structural/electronic characterization of one example. The coordination mode of
      the O 2-derived heme-Cu bridging group depends upon the copper-ligand
      environment, resulting in micro-(O 2 (2-)) side-on to Fe (III) and end-on to Cu
      (II) (micro-eta (2):eta (1)) binding for cases having N 4 tetradentate ligands
      but side-on/side-on (micro-eta (2):eta (2)) micro-peroxo coordination with
      tridentate copper chelates. The dynamics of the generation of Fe (III)-(O 2 (2-))
      Cu (II) complexes are known in some cases, including the initial formation of a
      short-lived superoxo (heme)Fe (III)(O 2 -) intermediate. Complexes with cross
      linked imidazole-phenol "cofactors" adjacent to the copper centers have also been
      described. Essential investigations of heme-copper-mediated reductive O-O bond
      cleavage chemistry are ongoing.

PMID- 17550226
TI  - Synthesis and in vitro testing of a pyropheophorbide-a-fullerene hexakis adduct
      immunoconjugate for photodynamic therapy.
AB  - The employment of carriers to enhance drug selectivity is one of the strategies
      to increase the efficacy and reduce the side effects of antitumor therapy. The
      concept of a modular carrier system (MCS) was developed to construct a complex
      drug having a high efficacy and selectivity. An MCS employs diverse units or
      modules: beside the therapeutic unit, an addressing unit (e.g., an antibody)
      serves to direct the drug to its target, and a multiplying unit has the role of
      increasing the number of biological active moieties the system can carry. In this
      paper, we report on the synthesis of a modular carrier system in which the role
      of multiplying unit is given to a [5:1]fullerene hexakis adduct. This fullerene
      hexaadduct has five malonate spacers which can bind two therapeutic units (the
      photosensitizer pyropheophorbide-a) each, for a total of ten, and a longer
      malonate spacer which serves for the conjugation to the addressing unit, the
      monoclonal antibody rituximab. Confocal microscopy studies using Epstein-Barr
      virus-transformed B-lymphocytes and Jurkat cells showed that the antibody
      conjugate conserves the affinity for its receptor (CD20) and its selectivity
      toward CD20 positive B-lymphocytes. On the contrary, the antibody-free complex
      did not show any bounding or intracellular uptake.

PMID- 17550227
TI  - MSNovo: a dynamic programming algorithm for de novo peptide sequencing via tandem
      mass spectrometry.
AB  - Tandem mass spectrometry (MS/MS) has become the experimental method of choice for
      high-throughput proteomics-based biological discovery. The two primary ways of
      analyzing MS/MS data are database search and de novo sequencing. In this paper,
      we present a new approach to peptide de novo sequencing, called MSNovo, which has
      the following advanced features. (1) It works on data generated from both LCQ and
      LTQ mass spectrometers and interprets singly, doubly, and triply charged ions.
      (2) It integrates a new probabilistic scoring function with a mass array-based
      dynamic programming algorithm. The simplicity of the scoring function, with only
      6-10 parameters to be trained, avoids the problem of overfitting and allows
      MSNovo to be adopted for other machines and data sets easily. The mass array data
      structure explicitly encodes all possible peptides and allows the dynamic
      programming algorithm to find the best peptide. (3) Compared to existing
      programs, MSNovo predicts peptides as well as sequence tags with a higher
      accuracy, which is important for those applications that search protein databases
      using the de novo sequencing results. More specifically, we show that MSNovo
      outperforms other programs on various ESI ion trap data. We also show that for
      high-resolution data the performance of MSNovo improves significantly. Supporting
      Information, executable files and data sets can be found at
      http://msms.usc.edu/supplementary/msnovo.

PMID- 17550228
TI  - Vapor deposition method for sensitivity studies on engineered surface-enhanced
      Raman scattering-active substrates.
AB  - The design and optimization of a vapor-phase analyte deposition method for limit
      of detection (LOD) studies on engineered surface-enhanced Raman scattering (SERS)
      active substrates is presented. The vapor deposition method was designed to
      overcome current challenges in quantitative analysis of lithographically produced
      SERS substrates that are relatively small (hundreds of square micrometers). A
      custom-built flow cell was used to deposit benzenethiol from the vapor phase onto
      SERS-active Ag thin films, as the control substrates, and nanoaperture arrays
      that were generated by electron-beam lithography. The surface coverage of
      benzenethiol as a function of time was monitored using the ring stretching mode
      1070-cm(-1) band and the trend was fit to Langmuir adsorption kinetics. The
      method was deemed reliable based on agreement between the LOD determined on the
      control substrates and previously reported values for those substrates.
      Application of the new method to a 20 x 20 microm(2) nanoaperture array yielded a
      LOD of 4.2 +/- 0.3 amol.

PMID- 17550229
TI  - Molecularly imprinted polymers as antibody mimics in automated on-line
      fluorescent competitive assays.
AB  - An automated molecularly imprinted sorbent based assay (MIA) for the rapid and
      sensitive analysis of penicillin-type beta-lactam antibiotics (BLAs) has been
      developed and optimized. The polymers were prepared using penicillin G procaine
      salt as template (PENGp) and a stoichiometric quantity of a urea-based functional
      monomer to target the single oxyanionic species in the template molecule. Highly
      fluorescent competitors (emission quantum yields of 0.4-0.95), molecularly
      engineered to contain pyrene labels while keeping intact the 6-aminopenicillanic
      acid moiety for efficient recognition by the cross-linked polymers, have been
      tested as analyte analogues in the competitive assay. Pyrenemethylacetamido
      penicillanic acid (PAAP) was the tagged antibiotic providing for the highest
      selectivity when competing with PenG for the specific binding sites in the
      molecularly imprinted polymer (MIP). Upon desorption from the MIP, the emission
      signal generated by the PAAP was related to the antibiotic concentration in the
      sample. The 50% binding inhibition concentration of penicillin G standard curves
      was at 1.81 x 10(-6) M PENG, and the detection limit was 1.97 x 10(-7) M. The
      sensor showed a dynamic range (normalized signal in the 20 to 80% range) from
      6.80 x 10(-7) to 7.21 x 10(-6) M (20-80% binding inhibition) PENG in
      acetonitrile:HEPES buffer 0.1 M at pH 7.5 (40:60, v/v) solutions. Competitive
      binding studies demonstrated various degrees of cross-reactivity with penicillin
      type beta-lactam antibiotics such as ampicillin (71%), oxacillin (66%),
      penicillin V (56%), amoxicillin (13%), and nafcillin (46%) and a lower response
      to other isoxazolyl penicillins such as cloxacillin (27%) and dicloxacillin
      (16%). The total analysis time was 14 min per determination, and the MIP reactor
      could be reused for more than 150 cycles without significant loss of recognition.
      The automatic MIA has been successfully applied to the direct analysis of
      penicillin G in spiked urine samples with excellent recoveries (mean value 92%).
      Results displayed by comparative analysis of the optimized MIA with a
      chromatographic procedure for penicillin G showed excellent agreement between
      both methods.

PMID- 17550230
TI  - Feedback effects in combined fast-scan cyclic voltammetry-scanning
      electrochemical microscopy.
AB  - Fast-scan cyclic voltammetry at scan rates between 5 and 1000 V s(-1) was
      performed at the tip of a scanning electrochemical microscope immersed in a
      solution of redox mediator. The effect of conducting and insulating substrates on
      the voltammetric signal was investigated as a function of scan rate and tip
      substrate distance. It was found that diffusional interactions between the tip
      and the substrate are greatest at lower scan rates and on the reverse sweep of
      the voltammogram. At the fastest scan rates used, the tip could be brought to
      with 1 microm of the substrate without appreciable perturbation of the
      voltammogram. By selecting scan rates and tip-substrate distances such that
      feedback effects were negligible, it was possible to image the diffusion layer of
      a 10 microm Pt substrate electrode. With the tip placed 1 microm above a
      biological cell, tip-substrate diffusional interactions were greatly diminished
      at a scan rate of 100 V s(-1) and absent at a scan rate of 1000 V s(-1). These
      results suggest conditions can be selected that allow chemical imaging of
      substrates without the feedback interactions typically encountered in scanning
      electrochemical microscopy.

PMID- 17550231
TI  - Real-time monitoring of single bacterium lysis and leakage events by
      chemiluminescence microscopy.
AB  - The small size of bacteria makes it difficult to study the biochemistry inside
      single cells. The amount of material inside is limited; therefore, an
      ultrasensitive method is required to interrogate single cells. Using a sensitive
      ICCD detector to record chemiluminescence (CL) from an optimized firefly
      luciferase-ATP bioluminescence reaction system, we report for the first time real
      time imaging of lysis and leakage of single bacterium with 10-s temporal
      resolution. Movies are generated to visualize how the cell membrane was damaged
      by phage lysis, antibiotics attack, or dehydration, as well as the wall repair
      and cell recovery processes. The results show single-cell variations that are not
      obtainable from bulk measurements, confirming that CL microscopy of luciferase
      expressing bacteria is a powerful tool for studying the fundamental biology of
      cells.

PMID- 17550232
TI  - Bench-top method for fabricating glass-sealed nanodisk electrodes, glass nanopore
      electrodes, and glass nanopore membranes of controlled size.
AB  - A simple benchtop method of fabricating glass-sealed nanometer-sized Au and Pt
      disk electrodes, glass nanopore electrodes, and glass nanopore membranes is
      reported. The synthesis of all three structures is initiated by sealing the tips
      of electrochemically sharpened Au and Pt microwires into glass membranes at the
      end of a soda lime or lead glass capillary. Pt and Au nanodisk electrodes are
      obtained by hand polishing using a high-input impedance metal oxide semiconductor
      field effect transistor (MOSFET)-based circuit to monitor the radius of the metal
      disk. Proper biasing of the MOSFET circuit, based on a numerical analysis of the
      polishing circuit impedance, allows for the reproducible fabrication of Pt disk
      electrodes of radii as small as 10 nm. Significantly smaller background currents
      in voltammetric measurements are obtained using lead glass capillaries, a
      consequence of the lower mobility of Pb(2+) (relative to Na(+)) in the glass
      matrix. Glass nanopore electrodes and glass nanopore membranes are fabricated,
      respectively, by removal of part or all of the metal sealed in the glass
      membranes. The nanostructures are characterized by atomic force microscopy,
      steady-state voltammetry, and ion conductivity measurements.

PMID- 17550233
TI  - A mass spectrometric study on the in vitro methylation of HMGA1a and HMGA1b
      proteins by PRMTs: methylation specificity, the effect of binding to AT-rich
      duplex DNA, and the effect of C-terminal phosphorylation.
AB  - HMGA1a and HMGA1b are members of one subfamily of non-histone chromosomal high
      mobility group (HMG) proteins. They bind to various DNA-related substrates,
      including the minor groove of AT-rich duplex DNA sequences, and have been
      postulated to be architectural transcription factors functioning in a wide
      variety of cellular processes. Post-translational modifications of HMGA1
      proteins, such as phosphorylation, acetylation, and methylation, are widely
      observed in tumor cells in vivo and correlated with the modulation of protein
      function. Here, we investigated the in vitro methylation of recombinant human
      HMGA1a and HMGA1b proteins by three members of the protein arginine
      methyltransferase (PRMT) family: PRMT1, PRMT3, and PRMT6. PRMT1 and PRMT3 showed
      a preference for methylating arginine residues in the first AT-hook of HMGA1
      proteins, whereas PRMT6 methylated mainly residues in the second AT-hook. The
      initial sites of methylation catalyzed by PRMT1 and PRMT3 were mapped by tandem
      mass spectrometry to be Arg25 and Arg23, respectively, while we confirmed that
      the initial sites of methylation catalyzed by PRMT6 were at Arg57 and Arg59. Our
      results also revealed that binding of HMGA1 proteins to AT-rich duplex DNA, but
      not GC-rich duplex DNA, significantly inhibited the methylation efficiency of all
      of the PRMTs toward HMGA1 proteins. Moreover, C-terminal constitutive
      phosphorylation of HMGA1 proteins induced by protein kinase CK2 did not have any
      appreciable effect on the in vitro methylation of HMGA1. Our results suggest that
      PRMT1 might be involved in the previously reported methylation of Arg25 in HMGA1a
      in vivo.

PMID- 17550234
TI  - Novel Zn2+ coordination by the regulatory N-terminus metal binding domain of
      Arabidopsis thaliana Zn(2+)-ATPase HMA2.
AB  - Arabidopsis thaliana HMA2 is a Zn2+ transporting P1B-type ATPase required for
      maintaining plant metal homeostasis. HMA2 and all eukaryote Zn2+-ATPases have
      unique conserved N- and C-terminal sequences that differentiate them from other
      P1B-type ATPases. Homology modeling and structural comparison by circular
      dichroism indicate that the 75 amino acid long HMA2 N-terminus shares the
      betaalphabetabetaalpha folding present in most P1B-type ATPase N-terminal metal
      binding domains (N-MBDs). However, the characteristic metal binding sequence
      CysXXCys is replaced by Cys17CysXXGlu21, a sequence present in all plant Zn2+
      ATPases. The isolated HMA2 N-MBD fragment binds a single Zn2+ (Kd 0.18 microM),
      Cd2+ (Kd 0.27 microM), or, with less affinity, Cu+ (Kd 13 microM). Mutagenesis
      studies indicate that Cys17, Cys18, and Glu21 participate in Zn2+ and Cd2+
      coordination, while Cys17 and Glu21, but not Cys18, are required for Cu+ binding.
      Interestingly, the Glu21Cys mutation that generates a CysCysXXCys site is unable
      to bind Zn2+ or Cd2+ but it binds Cu+ with affinity (Kd 1 microM) higher than
      wild type N-MBD. Truncated HMA2 lacking the N-MBD showed reduced ATPase activity
      without significant changes in metal binding to transmembrane metal binding
      sites. Likewise, ATPase activity of HMA2 carrying mutations Cys17Ala, Cys18Ala,
      and Glu21Ala/Cys was also reduced but showed a metal dependence similar to the
      wild type enzyme. These observations suggest that plant Zn2+-ATPase N-MBDs have a
      folding and function similar to Cu+-ATPase N-MBDs. However, the unique Zn2+
      coordination via two thiols and a carboxyl group provides selective binding of
      the activating metals to these regulatory domains. Metal binding through these
      side chains, although found in different sequences, appears as a common feature
      of both bacterial and eukaryotic Zn2+-ATPase N-MBDs.

PMID- 17550235
TI  - Crystal structure of the BARD1 BRCT domains.
AB  - The interaction of the breast tumor suppressor BRCA1 with the protein BARD1
      results in the formation of a heterodimeric complex that has ubiquitin ligase
      activity and plays central roles in cell cycle checkpoint control and DNA repair.
      Both BRCA1 and BARD1 possess a pair of tandem BRCT domains that interact in a
      phosphorylation-dependent manner with target proteins. We determined the crystal
      structure of the human BARD1 BRCT repeats (residues 568-777) at 1.9 A resolution.
      The composition and structure of the BARD1 phosphoserine-binding pocket P1 are
      strikingly similar to those of the BRCA1 and MDC1 BRCT domains, suggesting a
      similar mode of interaction with the phosphate group of the ligand. By contrast,
      the BARD1 BRCT selectivity pocket P2 exhibits distinct structural features,
      including two prominent histidine residues, His685 and His686, which may be
      important for ligand binding. The protonation state of these histidines has a
      marked effect on the calculated electrostatic potential in the vicinity of P2,
      raising the possibility that ligand recognition may be regulated by changes in
      pH. Importantly, the BARD1 BRCT structure provides insights into the mechanisms
      by which the cancer-associated missense mutations C645R, V695L, and S761N may
      adversely affect the structure and function of BARD1.

PMID- 17550237
TI  - Evidence for an intramolecular charge transfer state in 12'-apo-beta-caroten-12'
      al and 8'-apo-beta-caroten-8'-al: influence of solvent polarity and temperature.
AB  - The ultrafast excited-state dynamics of two carbonyl-containing carotenoids, 12'
      apo-beta-caroten-12'-al and 8'-apo-beta-caroten-8'-al, have been investigated by
      transient absorption spectroscopy in a systematic variation of solvent polarity
      and temperature. In most of the experiments, 12'-apo-beta-caroten-12'-al was
      excited at 430 nm and 8'-apo-beta-caroten-8'-al at 445 or 450 nm via the S0 -->
      S2 (11Ag- --> 11Bu+) transition. The excited-state dynamics were then probed at
      860 nm for 12'-apo-beta-caroten-12'-al and at 890 or 900 nm for 8'-apo-beta
      caroten-8'-al. The temporal evolution of all transient signals measured in this
      work can be characterized by an ultrafast decay of the S2 --> SN absorption at
      early times followed by the formation of a stimulated emission (SE) signal, which
      subsequently decays on a much slower time scale. We assign the SE signal to a low
      lying electronic state of the apocarotenals with intramolecular charge-transfer
      character (ICT --> S0). This is the first time that the involvement of an ICT
      state has been detected in the excited-state dynamics of a carbonyl carotenoid in
      nonpolar solvents such as n-hexane or i-octane. The amplitude ratio of ICT
      stimulated emission to S2 absorption was weaker in nonpolar solvents than in
      polar solvents. We interpret the results in terms of a kinetic model, where the
      S1 and ICT states are populated from S2 through an ultrafast excited-state
      branching reaction (tau2 < 120 fs). Delayed formation of a part of the stimulated
      emission is due to the transition S1 --> ICT (tau3 = 0.5-4.1 ps, depending on the
      solvent), which possibly involves a slower backward reaction ICT --> S1.
      Determinations of tau1 were carried out for a large set of solvents. Especially
      in 12'-apo-beta-caroten-12'-al, the final SE decay, assigned to the nonradiative
      relaxation ICT --> S0, was strongly dependent on solvent polarity, varying from
      tau1 = 200 ps in n-hexane to 6.6 ps in methanol. In the case of 8'-apo-beta
      caroten-8'-al, corresponding values were 24.8 and 7.6 ps, respectively. This
      indicates an increasing stabilization of the ICT state with increasing solvent
      polarity, resulting in a decreasing ICT-S0 energy gap. Tuning the pump wavelength
      from the blue wing to the maximum of the S0 --> S2 absorption band resulted in no
      change of tau1 in acetone and methanol. Additional measurements in methanol after
      excitation in the red edge of the S0 --> S2 band (480-525 nm) also show an almost
      constant tau1 with only a 10% reduction at the largest probe wavelengths. The
      temperature dependence of the tau1 value of 12'-apo-beta-caroten-12'-al was well
      described by Arrhenius-type behavior. The extracted apparent activation energies
      for the ICT --> S0 transitions were in general small (on the order of a few times
      RT), which is in the range expected for a radiationless process.

PMID- 17550236
TI  - Characterization of the physiological turnover of native and inactivated
      cytochromes P450 3A in cultured rat hepatocytes: a role for the cytosolic AAA
      ATPase p97?
AB  - Mammalian hepatic cytochromes P450 (P450s) are endoplasmic reticulum (ER)
      anchored hemoproteins engaged in the metabolism of numerous xeno- and
      endobiotics. P450s exhibit widely ranging half-lives, utilizing both autophagic
      lysosomal (ALD) and ubiquitin-dependent 26S proteasomal (UPD) degradation
      pathways. Although suicidally inactivated hepatic CYPs 3A and "native" CYP3A4 in
      Saccharomyces cerevisiae are degraded via UPD, the turnover of native hepatic
      CYPs 3A in their physiological milieu has not been elucidated. Herein, we
      characterize the degradation of native, dexamethasone-inducible CYPs 3A in
      cultured primary rat hepatocytes, using proteasomal (MG-132 and MG-262) and ALD
      [NH4Cl and 3-methyladenine (3-MA)] inhibitors to examine their specific
      degradation route. Pulse-chase with immunoprecipitation analyses revealed a basal
      52% 35S-CYP3A loss over 6 h, which was stabilized by both proteasomal inhibitors.
      By contrast, no corresponding CYP3A stabilization was detected with either ALD
      inhibitor NH4Cl or 3-MA. Furthermore, MG-262-induced CYP3A stabilization was
      associated with its polyubiquitylation, thereby verifying that native CYPs 3A
      were also degraded via UPD. To identify the specific participants in this
      process, cellular proteins were cross-linked in situ with paraformaldehyde (PFA)
      in cultured hepatocytes. Immunoblotting analyses of CYP3A immunoprecipitates
      after PFA-cross-linking revealed the presence of p97, a cytosolic AAA ATPase
      instrumental in the extraction and delivery of ubiquitylated ER proteins for
      proteasomal degradation. Such native CYP3A-p97 interactions were greatly
      magnified after CYP3A suicidal inactivation (which accelerates UPD), and/or
      proteasomal inhibition, and were confirmed by proteomic and confocal
      immunofluorescence microscopic analyses. These findings clearly reveal that
      native CYPs 3A undergo UPD and implicate a role for p97 in this process.

PMID- 17550238
TI  - Photoelectron spectroscopy and thermochemistry of tert-butylisocyanide
      substituted cobalt tricarbonyl nitrosyl.
AB  - A new organometallic complex, Co(CO)2NOtBuNC, was synthesized and investigated by
      photoelectron spectroscopy (PES) and threshold photoelectron photoion coincidence
      (TPEPICO) spectrometry in order to determine its ionization energy as well as the
      bond energies in the ionic forms. The assignment of the nine peaks in the PES was
      based on Kohn-Sham molecular orbital energies, and an adiabatic ionization energy
      of 7.30 +/- 0.05 eV was determined. In the TPEPICO experiment, the following 0 K
      onsets were determined for the various fragment ions: CoCONOtBuNC+ (8.17 +/- 0.05
      eV); CoNOtBuNC+ (9.01 +/- 0.05 eV); and CotBuNC+ (10.42 +/- 0.05 eV). Because the
      photon source did not extend above 14 eV, we could not observe the bare Co+ ion
      in the experiment. The heat of formation of the CotBuNC+ ion was estimated by ab
      initio and DFT calculations of the CoL+ + tBuNC --> CotBuNC+ + L (L = CO, NO,
      NH3, H2O, PMe3) substitution enthalpies.

PMID- 17550239
TI  - Accurate pair interaction energies for helium from supermolecular Gaussian
      geminal calculations.
AB  - Nonrelativistic clamped-nuclei pair interaction energy for ground-state helium
      atoms has been computed for 12 interatomic separations ranging from 3.0 to 9.0
      bohr. The calculations applied the supermolecular approach. The major part of the
      interaction energy was obtained using the Gaussian geminal implementation of the
      coupled-cluster theory with double excitations (CCD). Relatively small
      contributions from single, triple, and quadruple excitations were subsequently
      included employing the conventional orbital coupled-cluster method with single,
      double, and noniterative triple excitations [CCSD(T)] and the full configuration
      interaction (FCI) method. For three distances, the single-excitation contribution
      was taken from literature Gaussian-geminal calculations at the CCSD level. The
      orbital CCSD(T) and FCI calculations used very large basis sets, up to doubly
      augmented septuple- and sextuple-zeta size, respectively, and were followed by
      extrapolations to the complete basis set limits. The accuracy of the total
      interaction energies has been estimated to be about 3 mK or 0.03% at the minimum
      of the potential well. For the attractive part of the well, the relative errors
      remain consistently smaller than 0.03%. In the repulsive part, the accuracy is
      even better, except, of course, for the region where the potential goes through
      zero. For interatomic separations smaller than 4.0 bohr, the relative errors do
      not exceed 0.01%. Such uncertainties are significantly smaller than the expected
      values of the relativistic and diagonal Born-Oppenheimer contributions to the
      potential.

PMID- 17550240
TI  - Molecular tailoring and prediction of strongly ferromagnetically coupled
      trimethylenemethane-based nitroxide diradicals.
AB  - We have investigated the magnetic properties of four recently synthesized stable
      TMM-type nitroxide diradicals. Four new diradicals are proposed by tailoring one
      of the species in such a way that both conjugation and planarity increase. As a
      remarkable consequence, the intramolecular ferromagnetic exchange interaction was
      found to be quite high in the proposed radicals. The calculated coupling
      constants were in the range of +102 to +140 cm-1. The MO and spin density
      analysis are provided to interpret the exchange interactions. We observed the
      existence of intramolecular pi-pi-interactions for the species 2. This slightly
      increased the J value by shortening the length of the spacer between the two spin
      sources.

PMID- 17550241
TI  - Structure-activity relationships of a series of analogs of the endozepine
      octadecaneuropeptide (ODN(11)(-)(18)) on neurosteroid biosynthesis by
      hypothalamic explants.
AB  - We have previously shown that the endozepine octadecaneuropeptide (ODN)
      stimulates the biosynthesis of neurosteroids from frog hypothalamic explants. In
      the present study, we have investigated the structure-activity relationships of a
      series of analogs of the C-terminal octapeptide of ODN (OP) on neurosteroid
      formation. We found that OP and its cyclic analog cyclo1-8OP stimulate in a
      concentration-dependent manner the synthesis of various steroids including 17
      hydroxypregnenolone, progesterone, 17-hydroxyprogesterone and
      dehydroepiandrosterone. Deletion or Ala-substitution of the Arg1 or Pro2 residues
      of OP did not affect the activity of the peptide. In contrast, deletion or
      replacement of any of the amino acids of the C-terminal hexapeptide fragment
      totally abolished the effect of OP on neurosteroid biosynthesis. The present
      study indicates that the C-terminal hexapeptide of ODN/OP is the minimal sequence
      retaining full biological activity on steroid-producing neurons.

PMID- 17550244
TI  - Tridecanuclear and docosanuclear manganese phosphonate clusters with slow
      magnetic relaxation.
AB  - Two novel mixed-valent manganese phosphonate clusters
      [MnIIMnIII12O6(OH)6(O3PC6H11)10(py)6] (1) and
      [MnII4MnIII18O12(O3PC6H11)8(O2CCH3)22(H2O)6(py)2] (2) are reported in this paper.
      Complex 1 is the first carboxylate-free manganese phosphonate cluster. While
      compound 2 appears to be the largest manganese cluster thus far that contains
      phosphonate ligand. Both show slow magnetic relaxation behaviors.

PMID- 17550245
TI  - Resolving the aluminum ordering in aluminosilicates by a combined
      experimental/theoretical study of 27Al electric field gradients.
AB  - The discrimination between atomic species in light-element materials is a
      challenging question. An archetypal example is the resolution of the Al/Si
      ordering in aluminosilicates. Only an average long-range order can be deduced
      from powder X-ray or neutron diffraction, while magic-angle-spinning NMR provides
      an accurate picture of the short-range order. The long- and short-range orders
      thus obtained usually differ, hence raising the question of whether the
      difference between local and extended orders is intrinsic or caused by the
      difficulty of obtaining an accurate picture of the long-range order from
      diffraction techniques. In this communication we resolve this question for the
      monoclinic phases of BaAl2Si2O8 and SrAl2Si2O8 on the basis of 27Al NMR
      measurements and ab initio simulation of electric field gradient. Although the
      long- and short-range orders deduced from our XRD and NMR experiments differ,
      they become similar when the XRD atomic positions are optimized by ab initio
      electronic structure calculations.

PMID- 17550246
TI  - Gas phase formation of dense alkanethiol layers on GaAs(110).
AB  - We present a study of the growth and thermal stability of hexanethiol (C6) films
      on GaAs(110) by direct recoil spectroscopy with time-of-flight analysis. We
      compare our results with the better known case of C6 adsorption on Au(111). In
      contrast to the two-step adsorption kinetics observed for Au surfaces after
      lengthy exposures, data for C6 adsorption on the GaAs(110) surface are consistent
      with the formation of a single dense phase of C6 molecules at lower exposures. On
      the contrary, in solution preparation, dense phases can only be obtained on GaAs
      for long alkanethiols and after lengthy immersions. The C6 layer has a first
      desorption peak at 325 K, where partial desorption of the alkanethiol molecules
      takes place. Fits to the desorption curves result in a 1 eV adsorption energy, in
      agreement with a chemisorption process. Increasing the temperature to 500 K
      results in the S-C bond scission with only S remaining on the GaAs(110) surface.
      The possibility of forming dense, short-alkanethiol layers on semiconductor
      surfaces from the vapor phase could have a strong impact for a wide range of self
      assembled monolayer applications, with only minimal care not to surpass room
      temperature once the layer has been formed in order to avoid molecular
      desorption.

PMID- 17550247
TI  - Evolution of size and shape in the colloidal crystallization of gold
      nanoparticles.
AB  - The addition of dodecanethiol to a solution of oleylamine-stabilized gold
      nanoparticles in chloroform leads to aggregation of nanoparticles and formation
      of colloidal crystals. Based on results from dynamic light scattering and
      scanning electron microscopy we identify three different growth mechanisms:
      direct nanoparticle aggregation, cluster aggregation, and heterogeneous
      aggregation. These mechanisms produce amorphous, single-crystalline,
      polycrystalline, and core-shell type clusters. In the latter, gold nanoparticles
      encapsulate an impurity nucleus. All crystalline structures exhibit fcc or
      icosahedral packing and are terminated by (100) and (111) planes, which leads to
      truncated tetrahedral, octahedral, and icosahedral shapes. Importantly, most
      clusters in this system grow by aggregation of 60-80 nm structurally nonrigid
      clusters that form in the first 60 s of the experiment. The aggregation mechanism
      is discussed in terms of classical and other nucleation theories.

PMID- 17550248
TI  - Reversible oxidation state change in germanium(tetraphenylporphyrin) induced by a
      dative ligand: aromatic GeII(TPP) and antiaromatic GeIV(TPP)(pyridine)2.
AB  - Treatment of GeCl2(dioxane) with Li2(TPP)(OEt2)2 (TPP = tetraphenylporphyrin) in
      THF yields Ge(TPP), the first free Ge(II) porphyrin complex. In pyridine Ge(TPP)
      is converted to Ge(TPP)(py)2, an antiaromatic Ge(IV) complex, whereas in benzene
      the reaction is reversed, and pyridine dissociates from Ge(TPP)(py)2 to form
      Ge(TPP). That reversible reaction represents an unusual, if not unique, example
      of an oxidation-state change in a metal induced by coordination of a dative
      ligand. UV-vis and 1H NMR spectroscopy show that Ge(TPP) is an aromatic Ge(II)
      porphyrin complex, while the 1H NMR spectrum of Ge(TPP)(py)2 clearly indicates
      the presence of a strong paratropic ring current, characteristic of an
      antiaromatic compound. Both Ge(TPP) and Ge(TPP)(py)2 have been
      crystallographically characterized, and the antiaromaticity of Ge(TPP)(py)2 leads
      to alternating short and long C-C bonds along the 20-carbon periphery of its
      porphine ring system. Coordination of pyridine to Ge(TPP) greatly increases its
      reducing ability: the Ge(TPP)0/2+ redox potential is about +0.2 V, while the
      Ge(TPP)(py)2(0/+) redox potential is -1.24 V (both vs. ferrocene). The
      equilibrium constant of the reaction Ge(TPP) + 2 py = Ge(TPP)(py)2 in C6D6 is 22
      M-2. The germanium complex of the more electron-withdrawing tetrakis[3,5
      bis(trifluoromethyl)phenyl]porphyrin, Ge(TArFP), and its pyridine adduct
      Ge(TArFP)(py)2 were synthesized. The equilibrium constant of the reaction
      Ge(TArFP) + 2 py = Ge(TArFP)(py)2 in C6F6/C6D6 is 2.3 x 10(4) M-2. Density
      functional theory calculations are consistent with the experimental observation
      that M(TPP)(py)2 formation from M(TPP) and pyridine is most favorable for M=Si,
      borderline for Ge, and unfavorable for Sn.

PMID- 17550249
TI  - A surface functional monomer-directing strategy for highly dense imprinting of
      TNT at surface of silica nanoparticles.
AB  - This paper reports a surface functional monomer-directing strategy for the highly
      dense imprinting of 2,4,6-trinitrotoluene (TNT) molecules at the surface of
      silica nanoparticles. It has been demonstrated that the vinyl functional monomer
      layer of the silica surface can not only direct the selective occurrence of
      imprinting polymerization at the surface of silica through the copolymerization
      of vinyl end groups with functional monomers, but also drive TNT templates into
      the formed polymer shells through the charge-transfer complexing interactions
      between TNT and the functional monomer layer. The two basic processes lead to the
      formation of uniform core-shell TNT-imprinted nanoparticles with a controllable
      shell thickness and a high density of effective recognition sites. The high
      capacity and fast kinetics to uptake TNT molecules show that the density of
      effective imprinted sites in the nanoshells is nearly 5 times that of traditional
      imprinted particles. A critical value of shell thickness for the maximum
      rebinding capacity was determined by testing the evolution of rebinding capacity
      with shell thickness, which provides new insights into the effectiveness of
      molecular imprinting and the form of imprinted materials. These results reported
      here not only can find many applications in molecularly imprinting techniques but
      also can form the basis of a new strategy for preparing various polymer-coating
      layers on silica support.

PMID- 17550250
TI  - Heteroatomic deltahedral clusters: synthesis and structures of closo
      [Bi3Ni(4)(CO)6]3-, closo-[Bi4Ni4(CO)6]2-, the open cluster [Bi3Ni6(CO)9]3-, and
      the intermetalloid closo-[Nix@[Bi6Ni6(CO)8)]4-.
AB  - Reactions of ethylenediamine solutions of K4Bi5 with Ni(PPh3)2(CO)2 yielded four
      novel hetero-atomic Bi/Ni deltahedral clusters. Three of them, the 7-atom
      pentagonal bipyramidal [Bi3Ni4(CO)6]3-, the 8-atom dodecahedral [Bi4Ni4(CO)6]2-,
      and the Ni-centered or empty 12-atom icosahedral [Nix@[Bi6Ni6(CO)8]4-, are closo
      species according to both electron count and shape. The centered icosahedral
      cluster resembles packing in intermetallic compounds and belongs to the emerging
      class of intermetalloid clusters. The shape of the fourth cluster, [Bi3Ni6(CO)9]3
      , can be derived from the icosahedral Ni-centered [Ni@[Bi6Ni6(CO)8]4- by removal
      of three Bi- and one Ni-atoms of two neighboring triangular faces. The clusters
      were structurally characterized by single-crystal X-ray diffraction in compounds
      with potassium cations sequestered by 2,2,2-crypt or 18-crown-6 ether. They were
      also characterized in solution by electrospray mass spectrometry.

PMID- 17550251
TI  - FTIR studies of collagen model peptides: complementary experimental and
      simulation approaches to conformation and unfolding.
AB  - X-ray crystallography of collagen model peptides has provided high-resolution
      structures of the basic triple-helical conformation and its water-mediated
      hydration network. Vibrational spectroscopy provides a useful bridge for
      transferring the structural information from X-ray diffraction to collagen in its
      native environment. The vibrational mode most useful for this purpose is the
      amide I mode (mostly peptide bond C=O stretch) near 1650 cm-1. The current study
      refines and extends the range of utility of a novel simulation method that
      accurately predicts the infrared (IR) amide I spectral contour from the three
      dimensional structure of a protein or peptide. The approach is demonstrated
      through accurate simulation of the experimental amide I contour in solution for
      both a standard triple helix, (Pro-Pro-Gly)10, and a second peptide with a Gly -
      > Ala substitution in the middle of the chain that models the effect of a
      mutation in the native collagen sequence. Monitoring the major amide I peak as a
      function of temperature gives sharp thermal transitions for both peptides,
      similar to those obtained by circular dichroism spectroscopy, and the Fourier
      transform infrared (FTIR) spectra of the unfolded states were compared with
      polyproline II. The simulation studies were extended to model early stages of
      thermal denaturation of (Pro-Pro-Gly)10. Dihedral angle changes suggested by
      molecular dynamics simulations were made in a stepwise fashion to generate
      peptide unwinding from each end, which emulates the effect of increasing
      temperature. Simulated bands from these new structures were then compared to the
      experimental bands obtained as temperature was increased. The similarity between
      the simulated and experimental IR spectra lends credence to the simulation method
      and paves the way for a variety of applications.

PMID- 17550252
TI  - Structural assembly of multidomain proteins and protein complexes guided by the
      overall rotational diffusion tensor.
AB  - We present a simple and robust approach that uses the overall rotational
      diffusion tensor as a structural constraint for domain positioning in multidomain
      proteins and protein-protein complexes. This method offers the possibility to use
      NMR relaxation data for detailed structure characterization of such systems
      provided the structures of individual domains are available. The proposed
      approach extends the concept of using long-range information contained in the
      overall rotational diffusion tensor. In contrast to the existing approaches, we
      use both the principal axes and principal values of protein's rotational
      diffusion tensor to determine not only the orientation but also the relative
      positioning of the individual domains in a protein. This is achieved by finding
      the domain arrangement in a molecule that provides the best possible agreement
      with all components of the overall rotational diffusion tensor derived from
      experimental data. The accuracy of the proposed approach is demonstrated for two
      protein systems with known domain arrangement and parameters of the overall
      tumbling: the HIV-1 protease homodimer and Maltose Binding Protein. The accuracy
      of the method and its sensitivity to domain positioning are also tested using
      computer-generated data for three protein complexes, for which the experimental
      diffusion tensors are not available. In addition, the proposed method is applied
      here to determine, for the first time, the structure of both open and closed
      conformations of a Lys48-linked diubiquitin chain, where domain motions render
      impossible accurate structure determination by other methods. The proposed method
      opens new avenues for improving structure characterization of proteins in
      solution.

PMID- 17550253
TI  - Dissecting the proline effect: dissociations of proline radicals formed by
      electron transfer to protonated Pro-Gly and Gly-Pro dipeptides in the gas phase.
AB  - We report a combined experimental and computational study of the proline effect
      in model dipeptides Pro-Gly and Gly-Pro. Gas-phase protonated peptide ions were
      discharged by glancing collisions with potassium or cesium atoms at 3 keV
      collision energies, and the peptide radical intermediates and their dissociation
      products were analyzed following collisional ionization to anions. The charge
      reversal (+CR-) mass spectra of (Pro-Gly + H)+(1a+) and (Gly-Pro + H)+ (2a+)
      showed dramatic differences and thus provided a sensitive probe of ion structure.
      Whereas 1a+ completely dissociated upon charge inversion, 2a+ gave a
      nondissociated anion as the most abundant product. Ab initio and density
      functional theory calculations provided structures and vertical recombination
      energies (REvert) for 1a+ and 2a+. The recombination energies, REvert = 3.07 and
      3.36 eV for 1a+ and 2a+, respectively, were lower than the alkali metal
      ionization energies and indicated that the collisional electron transfer to the
      peptide ions was endoergic. Radical 1a* was found to exist in a very shallow
      local energy minimum, with transition state energies for loss and migration of H
      indicating very facile dissociation. In contrast, radical 2a* was calculated to
      spontaneously isomerize upon electron capture to a stable dihydroxycarbinyl
      isomer (2e*) that can undergo consecutive and competitive isomerizations by
      proline ring opening and intramolecular hydrogen atom transfers to yield stable
      radical isomers. Radical 2e* and its stable isomers were calculated to have
      substantial electron affinities and thus can form the stable anions that were
      observed in the +CR- mass spectra. The calculated TS energies and RRKM kinetic
      analysis indicated that peptide N-C alpha bond dissociations compete with
      pyrrolidine ring openings triggered by radical sites at both the N-terminal and C
      terminal sides of the proline residue. Open-ring intermediates were found in
      which loss of an H atom was energetically preferred over backbone dissociations.
      This provided an explanation for the proline effect causing low incidence of
      electron capture dissociations of N-C alpha bonds adjacent to proline residues in
      tryptic peptides and also for some peculiar behavior of proline-containing
      protein cation-radicals.

PMID- 17550255
TI  - Layer-by-layer assembly and spontaneous flocculation of oppositely charged oxide
      and hydroxide nanosheets into inorganic sandwich layered materials.
AB  - Exfoliated oxide nanosheets such as Ti0.91O2 and Ca2Nb3O10 and layered double
      hydroxide (LDH) nanosheets of Mg2/3Al1/3(OH)2 were restacked into inorganic
      sandwich layered materials. Sequential adsorption of these oppositely charged
      nanosheets from their colloidal suspensions yielded multilayer ultrathin films
      while their simple mixing produced lamellar flocculates. Eliminating carbonate
      ions from the reaction system was found to be essential for successfully
      achieving the sandwich structures. The flocculated materials as well as the films
      were characterized by atomic force microscopy (AFM), UV-visible absorption
      spectroscopy, X-ray photoelectron spectroscopy, X-ray diffraction (XRD),
      transmission electron microscopy (TEM), and chemical analysis, which all
      supported the formation of the ordered sandwich structures. AFM observations
      revealed alternate dense tiling of LDH nanosheets and oxide nanosheets onto a
      substrate surface. UV-visible absorption spectra exhibited progressive
      enhancement of optical density due to oxide nanosheets as a function of
      deposition cycles, providing strong evidence for regular growth of multilayer
      films. The combinations of Mg2/3Al1/3(OH)2/Ti0.91O2 and Mg2/3Al1/3(OH)2/Ca2Nb3O10
      produced XRD Bragg peaks having multilayer spacings of 1.2 and 2.0 nm,
      respectively. These basal spacing values are compatible with the sum of thickness
      of LDH nanosheets and corresponding oxide nanosheets. TEM images of flocculated
      samples displayed lamellar features with two different constituent layers
      appearing alternately.

PMID- 17550254
TI  - Heterobimetallic dioxygen activation: synthesis and reactivity of mixed Cu-Pd and
      Cu-Pt bis(mu-oxo) complexes.
AB  - Heterobimetallic CuPd and CuPt bis(mu-oxo) complexes have been prepared by the
      reaction of (PPh3)2MO2 (M=Pd, Pt) with LCu(I) precursors (L=beta-diketiminate and
      di- and triamine ligands) and characterized by low-temperature UV-vis, resonance
      Raman, and 1H and 31P[1H] NMR spectroscopy in conjunction with DFT calculations.
      The complexes decompose upon warming to yield OPPh3, and in one case this was
      shown to occur by an intramolecular process through crossover experiments using
      double-labeling (oxo and phosphine). The reactivity of one of the complexes,
      LMe2Cu(mu-O)2Pt(PPh3)2 (LMe2 = beta-diketiminate), with a variety of reagents
      including CO2, 2,4-di-tert-butylphenol, 2,4-di-tert-butylphenolate, [NH4][PF6],
      and dihydroanthracene, was compared to that of homometallic Pt2 and Cu2
      counterparts. Unlike typical [Cu2(mu-O)2]2+ cores which have electrophilic oxo
      groups, the oxo groups in the [Cu(mu-O)2Pt]+ core behave as bases and
      nucleophiles, similar to previously described Pt2 compounds. In addition,
      however, the [Cu(mu-O)2Pt]+ core is capable of oxidatively coupling 2,4-di-tert
      butylphenol and 2,4-di-tert-butylphenolate. Theoretical evaluation of the
      electron affinities, basicities, and H-atom transfer kinetics and thermodynamics
      of the Cu2 and CuM (M=Pd, Pt) cores showed that the latter are more basic and
      form stronger O-H bonds.

PMID- 17550256
TI  - Hydrazine fuels for bimetallic catalytic microfluidic pumping.

PMID- 17550257
TI  - An efficient synthesis of nitroalkenes by alkene cross metathesis: facile access
      to small ring systems.
AB  - A synthesis of highly functionalized nitroalkenes is reported that utilizes a
      cross metathesis (CM) reaction between simple aliphatic nitro compounds and a
      range of substituted alkenes. This chemistry offers a simple and attractive route
      to nitroalkenes that would otherwise be difficult to prepare, and that have a
      very useful application as precursors to a variety of heterocyclic entities.

PMID- 17550258
TI  - Modular synthesis of a new family of tripodal ligands, all-cis-1,2,3
      tris(diphenylphosphinomethyl)cyclopropane and relatives.
AB  - Bisbenzyl-protected all-cis-1,2,3-tris(hydroxymethyl)cyclopropane has been
      obtained in three steps from commercially available cis-2-butene-1,4-diol (75%
      overall yield) and used to prepare a number of all-cis-1,2,3-trisubstituted
      cyclopropane derivatives. Among them, the new tripodal ligand all-cis
      tris(diphenylphosphinomethyl)cyclopropane (TriCyp-PPP) has been demonstrated to
      furnish-with pi-allylpalladium chloride dimer-a highly active catalyst for the
      allylation of diethyl methylmalonate enolate with allyl acetate.

PMID- 17550259
TI  - New insights into NIS-promoted aminocyclization. Synthesis of decahydroquinolines
      from 2-allylcyclohexylamines.
AB  - Bishomoallylic secondary amines embodying the 2-allyl-N-benzylcyclohexylamine
      unit react with NIS to undergo cyclization through 6-endo processes in either the
      cis or trans series. Nevertheless, when the resulting cis-3
      iododecahydroquinolines are treated with Al2O3, the exo derivatives evolve into
      octahydroindoles and the endo derivatives keep the same backbone, the
      configuration being retained in the generated alcohols.

PMID- 17550260
TI  - Redox active, hybrid dendrimers containing Frechet- and Newkome-type blocks.
AB  - A new series of dendrimers was prepared by covalently attaching a Newkome
      dendron, a Frechet dendron, and a redox active, aminoferrocene group to a central
      triazine core. Growth of the Newkome dendron has a more pronounced effect on the
      half-wave potential for the one-electron oxidation of the ferrocene residue than
      growth of the Frechet dendron. All dendrimers show reversible or quasireversible
      voltammetric behavior at scan rates in the range 0.10-2.0 V s-1.

PMID- 17550261
TI  - Interaction of pyromellitic diimide derivatives with beta-cyclodextrin and
      anthracene-appended beta-cyclodextrin: rim binding vs inclusion complexation.
AB  - Complex formation of pyromellitic diimide derivatives with beta-cyclodextrin and
      anthracene-appended beta-cyclodextrin was studied with use of induced circular
      dichroism and 1H NMR spectroscopies. It is revealed that pyromellitic diimides
      form rim-binding type complexes with beta-CD and in these complexes the
      pyromellitic diimides lie just outside of the narrow rim of the CD. With
      anthracene-appended beta-CD the pyromellitic diimides form true inclusion
      complexes. Implications of the formation of rim-binding type complexes are also
      discussed.

PMID- 17550262
TI  - Hydrogen bonding affects the persistency of alkyl peroxy radicals.
AB  - The effect of 1,1,1,3,3,3-hexafluoro-2-phenylpropan-2-ol (HFPP) on the
      persistency of sec-alkyl peroxy radicals has been investigated. The formation of
      a hydrogen-bonding complex between HFPP and the radical resulted in a large
      increase in the lifetime of the radical. This variation was accompanied by a
      decrease in the g-value. An enthalpy change of -3.4 kcal mol-1 was estimated for
      the formation of the hydrogen-bonded complex.

PMID- 17550264
TI  - Effect of conjugated linoleic acids on the activity and mRNA expression of 5- and
      15-lipoxygenases in human macrophages.
AB  - Lipoxygenases are a family of non-heme enzyme dioxygenases. The role of
      lipoxygenases is synthesis of hydroperoxides of fatty acids, which perform
      signaling functions in the body. Studies on conjugated linoleic acids (CLAs) as
      fatty acids with a potential anti-atherosclerotic function have recently been
      initiated. The aim of the study was to test the effect of CLAs and linoleic acid
      on 5- and 15-lipoxygenase (5-LO, 15-LO-1) enzyme activity, their mRNA expression,
      and concentration in the cells. It was also desired to determine whether the CLAs
      are substrates for the enzymes. For the experiments monocytic cell line (THP-1)
      and monocytes obtained from human venous blood were used. Monocytes were
      differentiated to macrophages: THP-1 (CD14+) by PMA administration (100 nM for 24
      h) and monocytes from blood (CD14+) by 7-day cultivation with the autologous
      serum (10%). After differentiation, macrophages were cultured with 30 microM CLAs
      or linoleic acid for 48 h. The 15- and 5-lipoxygenase products were measured by
      HPLC method. mRNA expression and protein content were analyzed by real-time PCR
      and Western blot analysis. The in vitro studies proved that both CLA isomers are
      not substrates for 15-LO-1; in ex vivo studies hydroxydecadienoic acid (HODE)
      concentration was significantly reduced (p = 0.019). The trans-10,cis-12 CLA
      isomer reduced HODE concentration by 28% (p = 0.046) and the cis-9,trans-11 CLA
      isomer by 35% (p = 0.028). In macrophages obtained from THP-1 fatty acids did not
      change significantly mRNA expression of the majority of the investigated genes.
      CLAs did not change the content of 5-LO and 15-LO-1 proteins in macrophages
      obtained from peripheral blood. Linoleic acid induced 15-LO-1 expression (2.6
      times, p < 0.05). CLAs may perform the function of an inhibitor of lipoxygenase
      15-LO-1 activity in macrophages.

PMID- 17550265
TI  - Purification and characterization of an antifungal protein, C-FKBP, from Chinese
      cabbage.
AB  - An antifungal protein was isolated from Chinese cabbage (Brassica campestris L.
      ssp. pekinensis) by buffer-soluble extraction and two chromatographic procedures.
      The results of matrix-assisted laser desorption/ionization time-of-flight (MALDI
      TOF) mass spectrometry revealed that the isolated Chinese cabbage protein was
      identical to human FK506-binding protein (FKBP). A cDNA encoding FKBP was
      isolated from a Chinese cabbage leaf cDNA library and named C-FKBP. The open
      reading frame of the gene encoded a 154-amino acid polypeptide. The amino acid
      sequence of C-FKBP exhibits striking degrees of identity with the corresponding
      mouse (61%), human (60%), and yeast (56%) proteins. Genomic Southern blot
      analyses using the full-length C-FKBP cDNA probe revealed a multigene family in
      the Chinese cabbage genome. The C-FKBP mRNA was highly expressed in vegetative
      tissues. We also analyzed the antifungal and peptidyl-prolyl cis-trans isomerase
      activity of recombinant C-FKBP protein expressed in Escherichia coli. This
      protein inhibited pathogenic fungal strains, including Candida albicans, Botrytis
      cinerea, Rhizoctonia solani, and Trichoderma viride, whereas it exhibited no
      activity against E. coli and Staphylococcus aureus. These results suggest that
      recombinant C-FKBP is an excellent candidate as a lead compound for the
      development of antifungal agents.

PMID- 17550266
TI  - Nonenzymatic degradation of citrus pectin and pectate during prolonged heating:
      effects of pH, temperature, and degree of methyl esterification.
AB  - The underlying mechanisms governing nonenzymatic pectin and pectate degradation
      during thermal treatment have not yet been fully elucidated. This study
      determined the extent of nonenzymatic degradation due to beta-elimination, acid
      hydrolysis, and demethylation during prolonged heating of citrus pectins and its
      influence on physicochemical properties. Solutions of citrus pectins, buffered
      from pH 4.0 to 8.5, were heated at 75, 85, 95, and 110 degrees C for 0-300 min.
      Evolution of methanol and formation of reducing groups and unsaturated uronides
      were monitored during heating. Molecular weight and viscosity changes were
      determined through size exclusion chromatography and capillary viscometry,
      respectively. Results showed that at pH 4.5, the activation energies of acid
      hydrolysis, beta-elimination, and demethylation are 95, 136, and 98 kJ/mol,
      respectively. This means that at this pH, acid hydrolysis occurs more rapidly
      than beta-elimination. Furthermore, the rate of acid hydrolysis is diminished by
      higher levels of methyl esterification. Also, citrus pectin (93% esterified)
      degrades primarily via beta-elimination even under acidic conditions. Acid
      hydrolysis and beta-elimination caused significant reduction in relative
      viscosity and molecular weight.

PMID- 17550267
TI  - Digestion residues of typical and high-beta-glucan oat flours provide substrates
      for in vitro fermentation.
AB  - In vitro fermentabilities of the oat flour digestion residues (ODR) from two
      commercial oat lines with 4.7 and 5.3% beta-glucan and from two high-beta-glucan
      experimental lines with 7.6 and 8.1% beta-glucan were evaluated and compared with
      fermentations of lactulose, purified oat beta-glucan (POBG), and purified oat
      starch (POS). Substrates were fermented by using an in vitro batch fermentation
      system under anaerobic conditions for 24 h. The progress of the fermentation was
      studied by following the change in pH of the fermentation medium, production of
      short-chain fatty acids (SCFA) and gases, and consumption of carbohydrates. The
      substrate from the flour with the greatest amount of beta-glucan tended to have
      the greatest pH decline and the greatest total SCFA production. A significant
      correlation occurred between gas production and SCFA formation (R 2 = 0.89-0.99).
      Acetate was produced in the greatest amounts by all of the substrates except
      POBG, by which butyrate was produced in the greatest amount. More propionate and
      butyrate, but less acetate, were produced from high-beta-glucan ODR. With the
      given fermentation conditions, >80% of the total carbohydrate was depleted by the
      bacteria after 24 h. Glucose was the most rapidly consumed carbohydrate among
      other available monosaccharides in the fermentation medium. Overall, the high
      beta-glucan experimental lines provided the best conditions for optimal in vitro
      gut fermentations.

PMID- 17550268
TI  - Determination of tetracycline antibiotic residues in edible swine tissues by
      liquid chromatography with spectrofluorometric detection and confirmation by mass
      spectrometry.
AB  - A sensitive and specific method is described for the simultaneous determination
      of oxytetracycline, tetracycline (TC), and chlortetracycline residues in edible
      swine tissues, by combining liquid chromatography with spectrofluorometric and
      mass spectrometry detection. The procedure involved a preliminary extraction with
      EDTA-McIlvaine buffer acidified at pH 4.0, followed by solid-phase extraction
      cleanup using a polymeric sorbent. The liquid chromatography analysis was
      performed with spectrofluorometric detection after postcolumn derivatization with
      magnesium ions. The limits of quantification were 50 microg/kg for muscle and 100
      microg/kg for kidney tissues. The recovery values were greater than 77.8% for
      muscle and 65.1% for kidney. The method has been successfully used for the
      quantification of tetracyclines in swine tissues samples. The selective liquid
      chromatography mass spectrometric analysis for confirmation of oxytetracycline in
      one positive swine muscle sample was made by atmospheric pressure chemical
      ionization (APCI). The APCI mass spectra of the TCs gave the protonated molecular
      ion and two typical fragment ions, required for their confirmation in single ion
      monitoring scan mode in animal tissues.

PMID- 17550269
TI  - Polyphenol composition and antioxidant activity in strawberry purees; impact of
      achene level and storage.
AB  - In this study the impact of achenes on polyphenolic compounds, ascorbic acids,
      and antioxidant activities in strawberry purees at production and after storage
      at 6 and 22 degrees C for 8 and 16 weeks was investigated. Strawberry purees were
      made from flesh, berry, and achene-enriched homogenate and contained 0, 1.2, and
      2.9% achenes, respectively. At production, strawberry purees made from flesh
      contained more anthocyanins, p-coumaroyl glycosides, and ascorbic acids, whereas
      increasing achene levels caused increasing levels of ellagic acid derivatives,
      proanthocyanidins, flavonols, total phenolics (TP), and antioxidant activities.
      In addition, the anthocyanins, TP, and ferric reducing ability power (FRAP) in
      purees with more achenes were better retained during storage. Ascorbic acids and
      anthocyanins declined rapidly during storage, whereas other polyphenols and
      antioxidant activities were more stable; that is, the contributions from
      anthocyanins and ascorbic acids to TP and antioxidant activities decreased. The
      findings that achenes contributed significantly to polyphenol content and
      stability of strawberry purees may be interesting in a nutritional and, thus,
      commercial, perspective.

PMID- 17550270
TI  - Inhibition of inducible nitric oxide synthase expression by an acetonic extract
      from Feijoa sellowiana Berg. fruits.
AB  - Feijoa sellowiana Berg. fruits and especially the acetonic extract have been
      shown to possess biological activities, although the responsible compounds have
      never been identified. The present study was designed to evaluate the anti
      inflammatory activity of an acetonic extract from F. sellowiana Berg. fruits on
      the nitric oxide (NO) pathway, which plays an important role in inflammation. To
      this aim the J774 cell line, which expresses inducible nitric oxide synthase
      (iNOS) following stimulation with lipopolysaccharide (LPS), has been utilized,
      and the effects of this extract and its fractions on NO production, iNOS protein
      expression, and signal pathways involved in its regulation have been evaluated.
      This study demonstrates that at least some part of the anti-inflammatory activity
      of the acetonic extract is due to the suppression of NO production by flavone and
      stearic acid. The mechanism of this inhibition seems to be related to an action
      on the expression of the enzyme iNOS through the attenuation of nuclear factor
      kappaB (NF-kappaB) and/or mitogen-activated protein kinase (MAPK) activation.

PMID- 17550271
TI  - The relationship of the redox potentials of thioredoxin and thioredoxin reductase
      from Drosophila melanogaster to the enzymatic mechanism: reduced thioredoxin is
      the reductant of glutathione in Drosophila.
AB  - Thioredoxin reductase from Drosophila melanogaster (DmTrxR) catalyzes the
      reversible transfer of reducing equivalents between NADPH and thioredoxin (Trx),
      a small protein that is involved in a wide variety of biological redox processes.
      The catalysis involves three essential redox states of the enzyme: the oxidized
      form of DmTrxR (Eox), the 2-electron-reduced forms (EH2), and the 4-electron
      reduced forms (EH4). In the present work, the macroscopic redox potentials of
      Eox/EH2 and EH2/EH4 couples were determined to be -272 +/- 5 mV for Em(Eox/EH2)
      and -298 +/- 11 mV for Em(EH2/EH4) on the basis of redox equilibria between
      DmTrxR and NADH. The value for Em(EH2/EH4) obtained from the steady-state
      kinetics of the TrxR-catalyzed reaction between NADPH and D. melanogaster Trx-2
      (DmTrx-2) was reasonably consistent with that based on redox equilibria. The
      redox potential of the Trx-(S)2/Trx-(SH)2 couple from D. melanogaster Trx-2
      (DmTrx-2) was calculated to be -275.4 +/- 0.3 mV by using the Nernst equation and
      the Keq for the equilibrium of the reaction involving NADP/NADPH and Trx-(S)2/Trx
      (SH)2. For the accurate determination of the Keq, an improved protocol has been
      developed to minimize errors that can be introduced by using starting
      concentrations far from equilibrium of the TrxR-catalyzed reaction between NADPH
      and Trx. This improved approach gives an Em of -284.2 +/- 1.0 mV for Escherichia
      coli Trx and -271.9 +/- 0.4 mV for Plasmodium falciparum Trx, which agree well
      with published values (-283 or -285 mV and -270 mV, respectively). The redox
      potentials determined herein provide further direct evidence for the proposed
      catalytic mechanism of DmTrxR, and cast new light on the essential role of the
      DmTrx system in cycling GSSG/GSH and maintaining the intracellular redox
      homeostasis in D. melanogaster where glutathione reductase is absent.

PMID- 17550272
TI  - Characterization of the beta-lactam antibiotic sensor domain of the MecR1 signal
      sensor/transducer protein from methicillin-resistant Staphylococcus aureus.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) has evolved two mechanisms for
      resistance to beta-lactam antibiotics. One is production of a beta-lactamase, and
      the other is that of penicillin-binding protein 2a (PBP 2a). The expression of
      these two proteins is regulated by the bla and mec operons, respectively. BlaR1
      and MecR1 are beta-lactam sensor/signal transducer proteins, which experience
      acylation by beta-lactam antibiotics on the cell surface and transduce the signal
      into the cytoplasm. The C-terminal surface domain of MecR1 (MecRS) has been
      cloned, expressed, and purified to homogeneity. This protein has been
      characterized by documenting that it has a critical and unusual Nzeta
      carboxylated lysine at position 394. Furthermore, the kinetics of interactions
      with beta-lactam antibiotics were evaluated, a process that entails
      conformational changes for the protein that might be critical for the signal
      transduction event. Kinetics of acylation of MecRS are suggestive that signal
      sensing may be the step where the two systems are substantially different from
      one another.

PMID- 17550273
TI  - A novel 4-oxo-2(E)-nonenal-derived endogenous thiadiazabicyclo glutathione adduct
      formed during cellular oxidative stress.
AB  - Cellular oxidative stress causes increased lipid peroxidation with the
      concomitant formation of DNA and protein reactive bifunctional electrophiles.
      Glutathione (GSH) detoxifies these bifunctional electrophiles by forming GSH
      adducts. Several years ago we discovered 4-oxo-2(E)-nonenal (ONE) as a major
      bifunctional electrophile derived from lipid hydroperoxides. We have now made the
      unexpected discovery that glutathione-S-transferase (GST)-mediated GSH addition
      to ONE occurs primarily to C-1 of the alpha,beta-unsaturated ketone rather than
      to C-3 of the alpha,beta-unsaturated aldehyde. The resulting intermediate rapidly
      undergoes two intramolecular cyclizations followed by two separate dehydration
      reactions to provide an unusual thiadiazabicyclo-ONE-GSH adduct (TOG).
      Quantification of intracellular TOG was performed using stable isotope dilution
      liquid chromatography-multiple reaction monitoring/mass spectrometry after the
      addition of ONE to cells or as an endogenously derived adduct during peroxide
      induced oxidative stress. TOG represents the first member of a new class of
      thiadiazabicyclo GSH adducts that are formed through GST-mediated addition of GSH
      to reactive intermediates containing the ONE motif during intracellular oxidative
      stress. ONE formation can potentially result from free radical pathways as well
      as cyclooxygenase- and lipoxygenase-mediated pathways. Its aldo-keto reductase
      mediated reduction product, 4-oxo-2(E)-nonenol (ONO), was also formed and
      converted to GSH adducts similar to those formed by 4-hydroxy-2(E)-nonenal (HNE).
      ONO is isomeric with HNE; therefore, protein and peptide adducts ascribed to
      arise solely from reactions with endogenous HNE will need to be re-appraised.

PMID- 17550275
TI  - Contrasting behavior of zwitterionic and cationic polymers bound to anionic
      liposomes.
AB  - Zwitterionic polymers were prepared by quaternizing polyvinylpyridine (DP = 1100)
      with bromoacids (Br(CH2)nCOOH, where n = 1, 2, 3, and 5). The resulting polymers
      were then added to unilamellar liposomes composed of egg lecithin or
      dipalmitoylphosphatidylcholine admixed with 20 mol % of cardiolipin (a
      phospholipid with two negative charges). These systems were compared (along with
      polyethylvinylpyridinium chloride, a polycation) by light scattering,
      electrophoretic mobility, fluorescence, and high-sensitivity differential
      scanning calorimetry. The external zwitterionic polymers induce no flip-flop of
      cardiolipin from the inner leaflet to the outer leaflet as does the polycation.
      Aside from this similarity, the four zwitterionic polymers all behave differently
      from each other toward the anionic liposomes: (a) For n = 1, there is no
      detectable interaction between the polymer and the liposomes. (b) For n = 2,
      electrostatic attraction induces polymer-liposome association (reversed by the
      addition of NaCl) that maintains the original negative charge on the liposome.
      Aggregation of the liposomes accompanies polymer adsorption. (c) For n = 3,
      electrostatic binding also occurs along with aggregation. However, the binding is
      so strong that NaCl is unable to induce polymer/liposome dissociation. (d) For n
      = 5, there is polymer binding and NaCl-promoted dissociation but no substantial
      aggregation. These differences among the closely related polymers are discussed
      and analyzed in molecular terms.

PMID- 17550276
TI  - Using the bending beam model to estimate the elasticity of diphenylalanine
      nanotubes.
AB  - The core recognition motif of the amyloidogenic beta-amyloid polypeptide,
      diphenylalanine peptide, has previously been shown to self-assemble into
      discrete, well-ordered, stiff nanotubes under mild conditions. The nanotubes keep
      the same morphology from room temperature up to 100 degrees C. In the presented
      study, we applied the bending beam model to atomic force microscopy images of
      diphenylalanine nanotubes suspended across cavities and obtained the Young's
      modulus 27 +/- 4 GPa and the shear modulus 0.21 +/- 0.03 GPa. We also showed that
      the elasticity of these nanotubes is stable within the same temperature range and
      at relative humidity from 0% to 70%. This study furthers our understanding of the
      structure and properties of these nanotubes, which are important for their
      potential applications in biotechnology.

PMID- 17550277
TI  - Sample size and replication in 2D gel electrophoresis studies.
AB  - Two-dimensional gel electrophoresis can be an expensive technology, and many
      studies are based on a modest number of replicates. It is important that the
      statistical power is sufficient to detect protein expression differences of
      interest. This paper reviews the application of power calculations and considers
      how other issues affect the choice of sample size. The important distinction
      between biological and technical replication is made, and the superiority of the
      former is emphasized.

PMID- 17550278
TI  - Excitation energy transfer in the photosystem II core antenna complex CP43
      studied by femtosecond visible/visible and visible/mid-infrared pump probe
      spectroscopy.
AB  - Excitation energy transfer in the Photosystem II core antenna complex CP43 has
      been investigated by vis/vis and vis/mid-IR pump-probe spectroscopy with the aim
      of understanding the relation between the dynamics of energy transfer and the
      structural arrangement of individual chlorophyll molecules within the protein.
      Energy transfer was found to occur on time scales of 250 fs, 2-4 ps, and 10-12
      ps. The vis/mid-IR difference spectra show that the excitation is initially
      distributed over chlorophylls located in environments with different polarity,
      since two 9-keto C=O stretching bleachings, at 1691 and 1677 cm-1, are observable
      at early delay times. Positive signals in the initial difference spectra around
      1750 and 1720 cm-1 indicate the presence of a charge transfer state between
      strongly interacting chlorophylls. We conclude, both from the spectral behavior
      in the visible when the annihilation processes are increased and from the vis/mid
      IR data, that there are two pigments (one absorbing around 670 nm and one at 683
      nm) which are not connected to the other pigments on a time scale faster than 10
      20 ps. Since, in the IR, on a 10 ps time scale the population of the 1691 cm-1
      mode almost disappears, while the 1677 cm-1 mode is still significantly
      populated, we can conclude that at least some of the red absorbing pigments are
      located in a polar environment, possibly forming H-bonds with the surrounding
      protein.

PMID- 17550279
TI  - Effect of headgroup on DNA-cationic surfactant interactions.
AB  - The interaction behavior of DNA with different types of hydroxylated cationic
      surfactants has been studied. Attention was directed to how the introduction of
      hydroxyl substituents at the headgroup of the cationic surfactants affects the
      compaction of DNA. The DNA-cationic surfactant interaction was investigated at
      different charge ratios by several methods like UV melting, ethidium bromide
      exclusion, and gel electrophoresis. Studies show that there is a discrete
      transition in the DNA chain from extended coils (free chain) to a compact form
      and that this transition does not depend substantially on the architecture of the
      headgroup. However, the accessibility of DNA to ethidium bromide is preserved to
      a significantly larger extent for the more hydrophilic surfactants. This was
      discussed in terms of surfactant packing. Observations are interpreted to reflect
      that the surfactants with more substituents have a larger headgroup and therefore
      form smaller micellar aggregates; these higher curvature aggregates lead to a
      less efficient, "patch-like" coverage of DNA. The more hydrophilic surfactants
      also presented a significantly lower cytotoxicity, which is important for
      biotechnological applications.

PMID- 17550280
TI  - Linear solvation energy correlation of the solvatochromic response of amino acid
      functionalized chromophores.
AB  - Solvatochromism of the long wavelength band in the electronic absorption spectra
      of N-(4-nitrophenyl)-L-proline, NLP, N-(4-nitrophenyl)-D-proline, NDP, and N-(4
      nitro-phenyl)-trans-4-hydroxy-L-proline, NHP, was studied and quantitatively
      described with Kamlet-Taft solvent polarity parameters. To evaluate the
      environmental effects for NLP, NDP, and NHP, the UV-vis spectroscopic behavior of
      these compounds was also investigated as pure crystals, as a guest in 2,6-O
      dimethyl-beta-cyclodextrin, and also when adsorbed on Aerosil 300 silica
      particles from nonhydrogen-bond accepting solvents. Excellent Kamlet-Taft
      solvatochromic correlations were established for the three compounds in most
      solvents. Multiparameter correlations show the existence of specific solute
      solvent interactions. A strong positive solvatochromic behavior was found for
      these compounds, indicating that their dipole moments were higher in the excited
      singlet state than in the ground state.

PMID- 17550281
TI  - On use of the Amber potential with the Langevin dipole method.
AB  - Inclusion of solvent effects in biomolecular simulations is most ideally done
      using explicit methods, as they are able to capture the heterogeneous environment
      typical of biomolecules and systems involving them (e.g., proteins at solid
      interfaces). Common explicit methods based on molecular solvent models (e.g., TIP
      and SPC models) and molecular dynamic or Monte Carlo simulation are
      computationally expensive and are, therefore, not well-suited to situations where
      many simulations are required (e.g., in the ab initio structure prediction or
      design contexts). In such cases, more coarse-grained explicit approaches such as
      the Langevin dipole (LD) method of Warshel and co-workers are more appropriate.
      The recent incarnations of the LD method appear to produce good solvation free
      energy estimates. These incarnations use charges and solute structures obtained
      from high-level quantum mechanics simulations. As such an approach is clearly not
      possible for larger solutes or when many structures are to be considered, an
      alternative must be sought. One possibility is to use structures and charges
      derived from an existing analytical potential model-we report on such a coupling
      here with the Amber potential model. The accuracy and computational performance
      of this hybrid approach, which we term LD-Amber to distinguish it from previous
      incarnations of the LD method, was assessed by comparing results obtained from
      the approach with those from experiment and other theoretical methods for the
      solvation of 18 amino acid analogues and the alanine dipeptide. This comparison
      shows that the LD-Amber approach can yield results in line with experiment both
      qualitatively and quantitatively and is as accurate as other explicit methods
      while being computationally much cheaper.

PMID- 17550282
TI  - Inducing pH responsiveness via ultralow thiol content in polyacrylamide
      (micro)gels with labile crosslinks.
AB  - Here we present the synthesis and characterization of pH responsive
      polyacrylamide microgels, synthesized via free radical polymerization of
      acrylamide and bis (acryloylcystamine) (BAC). The gels were made with ultralow
      amounts of thiol functional groups incorporated into the polymer. The resulting
      gel monoliths were mechanically chopped into microgel particles with size
      distributions ranging from 80 to 200 mum. The gels exhibit an interesting
      reversible pH-dependent rheological behavior which led to gelling of the
      colloidal suspension when the pH was increased, and a low-viscosity suspension
      was obtained when the pH was taken back to the original value. The viscosity of
      the colloidal system containing MBA crosslinked microgels remained insensitive to
      pH. This observation motivated further analysis; viscosity measurements of the
      highly viscous (gel-like) state of the BAC crosslinked microgel colloidal
      suspension were carried out to further understand the rheological behavior of the
      colloidal system. Electrophoretic mobility measurements as function of pH of the
      BAC and MBA crosslinked colloidal polyacrylamide microgel suspensions were
      performed. The swelling behavior of the microgels for both colloidal systems was
      also determined as function of pH using static light scattering. This swelling
      behavior was used to rationalize the observed rheological behavior. The work
      presented here demonstrates that free thiol groups present within a polymer gel
      matrix confer pH responsive behavior to the gel in solution. The viscosity of a
      BAC crosslinked microgel suspension was also measured under reducing conditions.
      The viscosity of the microgel suspension reduced with time, due to the breakage
      of the disulfide bonds in the crosslinkers.

PMID- 17550283
TI  - Solvation of sodium chloride in the 1-butyl-3-methyl-imidazolium
      bis(trifluoromethylsulfonyl)imide ionic liquid: a molecular dynamics study.
AB  - We report molecular dynamics studies on the solvation of sodium chloride in the 1
      butyl-3-methyl-imidazolium bis(trifluoromethylsulfonyl)imide ionic liquid
      ([BMI][Tf2N] IL). We first consider the potential of mean force for dissociating
      a single Na+Cl- ion pair, showing that the latter prefers to be undissociated
      rather than dissociated (by ca. 9 kcal/mol), with a free energy barrier of ca. 5
      kcal/mol (at d approximately 5.2 A) for the association process. The preference
      for Na+Cl- association is also observed from a 100 ns molecular dynamics
      simulation of a concentrated solution, where the Na+Cl- ions tend to form
      oligomers and microcrystals in the IL. Conversely, the simulation of Na13Cl14-
      and Na14Cl13+ cubic microcrystals (with, respectively, Cl- and Na+ at the
      vertices) does not lead to dissolution in the IL. Among these, Na14Cl13+ is found
      to be better solvated than Na13Cl14-, mainly due to the stronger Na+...Tf2N-
      interactions as compared to the Cl-...BMI+ interactions at the vertices of the
      cube. We finally consider the solid/liquid interface between the 100 face of NaCl
      and the IL, revealing that, in spite of its polar nature, the crystal surface is
      solvated by the less polar IL components (CF3(Tf2N) and butyl(BMI) groups) rather
      than by the polar ones (O(Tf2N) and imidazolium(BMI) ring). Specific ordering at
      the interface is described for both Tf2N- anions and BMI+ cations. In the first
      IL layer, the ions are rather parallel to the surface, whereas in the second
      "layer" they are more perpendicular. A similar IL structure is found at the
      surface of the all-neutral Na0Cl0 solid analogue, confirming that the solvation
      of the crystal is rather "apolar", due to the mismatch between the IL and the
      crystal ions. Several comparisons with water, methanol, or different BMI+-based
      ILs as solvents are presented, allowing us to better understand the specificity
      of the ionic liquid-NaCl interactions.

PMID- 17550284
TI  - Cooperativity in ordinary ice and breaking of hydrogen bonds.
AB  - The total interaction energy between two H-bonded water molecules in a condensed
      phase is composed of a binding energy between them and an energy due to a
      cooperative effect. An approximate simple expression is suggested for the
      dependence of the interaction energy between two H-bonded water molecules on the
      number of neighboring water molecules with which they are H-bonded. Using this
      expression, the probabilities of breaking a H bond with various numbers of H
      bonded neighbors are estimated. These probabilities are used in computer
      simulations of the breaking of specified fractions of H bonds in an ordinary
      (hexagonal) ice. A large "piece" of hexagonal ice (up to 8 millions molecules) is
      built up, and various percentages of H bonds are considered broken. It is shown
      that 62-63% of H bonds must be broken in order to disintegrate the "piece" of ice
      into disconnected clusters. This value is only a little larger than the
      percolation threshold (61%) predicted both by the percolation theory for
      tetrahedral ice and by simulations in which all H bonds were considered equally
      probable to be broken. When the percentage of broken bonds is smaller than 62
      63%, there is a network of H-bonded molecules which contains the overwhelming
      majority of water molecules. This result contradicts some models of water which
      consider that water consists of a mixture of water clusters of various sizes. The
      distribution of water molecules with unequal probabilities for breaking is
      compared with the simulation involving equal probabilities for breaking. It was
      found that in the former case, there is an enhanced number of water monomers
      without H bonds, that the numbers of 2- and 3-bonded molecules are smaller, and
      the number of 4-bonded molecules is larger than in the latter case.

PMID- 17550285
TI  - In silico prediction of drug solubility. 3. Free energy of solvation in pure
      amorphous matter.
AB  - The solubility of drugs in water is investigated in a series of papers. In this
      work, we address the process of bringing a drug molecule from the vapor into a
      pure drug amorphous phase. This step enables us to actually calculate the
      solubility of amorphous drugs in water. In our general approach, we, on one hand,
      perform rigorous free energy simulations using a combination of the free energy
      perturbation and thermodynamic integration methods. On the other hand, we develop
      an approximate theory containing parameters that are easily accessible from
      conventional Monte Carlo simulations, thereby reducing the computation time
      significantly. In the theory for solvation, we assume that DeltaG* = DeltaGcav +
      ELJ + EC/2, where the free energy of cavity formation, DeltaGcav, in pure drug
      systems is obtained using a theory for hard-oblate spheroids, and ELJ and EC are
      the Lennard-Jones and Coulomb interaction energies between the chosen molecule
      and the others in the fluid. The theoretical predictions for the free energy of
      solvation in pure amorphous matter are in good agreement with free energy
      simulation data for 46 different drug molecules. These results together with our
      previous studies support our theoretical approach. By using our previous data for
      the free energy of hydration, we compute the total free energy change of bringing
      a molecule from the amorphous phase into water. We obtain good agreement between
      the theory and simulations. It should be noted that to obtain accurate results
      for the total process, high precision data are needed for the individual
      subprocesses. Finally, for eight different substances, we compare the
      experimental amorphous and crystalline solubility in water with the results
      obtained by the proposed theory with reasonable success.

PMID- 17550286
TI  - How solvent controls electronic energy transfer and light harvesting.
AB  - The way that solvent (or host medium) modifies the rate of electronic energy
      transfer (EET) has eluded researchers for decades. By applying quantum chemical
      methods that account for the way solvent (in general any host medium including
      liquid, solid, or protein, etc.) responds to the interaction between transition
      densities, we quantify the solvent screening. We find that it attains a striking
      exponential attenuation at separations less than about 20 A, thus interpolating
      between the limits of no apparent screening and a significant attenuation of the
      EET rate. That observation reveals a previously unidentified contribution to the
      distance dependence of the EET rate.

PMID- 17550287
TI  - Physical properties of polyurethane plastic sheets produced from polyols from
      canola oil.
AB  - Polyurethane (PUR) plastic sheets were prepared by reacting polyols synthesized
      from canola oil with aromatic diphenylmethane diisocyanate. The properties of the
      material were measured by dynamic mechanical analysis (DMA), differential
      scanning calorimetry (DSC), and thermogravimetric analysis (TGA) as well as
      tensile properties measurements. The effect of stoichiometric balance (i.e.,
      OH/NCO molar ratio) on the final properties was evaluated. The concentration of
      elastically active network chains (EANCs), nue, of the polymer networks was
      calculated using rubber elasticity theory. The glass transition temperatures (Tg)
      for the plastic sheets with OH/NCO molar ratios of 1.0/1.0, 1.0/1.1, and 1.0/1.2
      were found to be 23, 41, and 43 degrees C, respectively. The kinetic studies of
      the degradation process of the PUR plastics showed three well-defined steps of
      degradation. The PUR plastic sheets with OH/NCO molar ratio 1.0/1.1 had the
      highest nue, lowest number-average molecule weight between cross-links, MC, and
      excellent mechanical properties, indicating that this is the optimum ratio in the
      PUR formulations.

PMID- 17550288
TI  - Lipase-catalyzed copolymerization of omega-pentadecalactone with p-dioxanone and
      characterization of copolymer thermal and crystalline properties.
AB  - Candida antarctica Lipase B (CALB), a metal-free enzyme, was successfully
      employed as catalyst for ring-opening copolymerization of omega-pentadecalactone
      (PDL) with p-dioxanone (DO) under mild reaction conditions (<80 degrees C,
      atmospheric pressure). Poly(PDL-co-DO) with high molecular weight (Mw > 30 000)
      and a wide range of comonomer contents was synthesized using various PDL/DO feed
      ratios. During the copolymerization reaction, large ring PDL was found to be more
      reactive than its smaller counterpart DO, resulting in higher PDL/DO unit ratios
      in polymer chains than the corresponding PDL/DO monomer ratios in the feed. The
      copolymers were typically isolated in 50-90 wt % yields as the monomer conversion
      was limited by the equilibrium between monomers and copolymer. 1H and 13C NMR
      analysis on poly(PDL-co-DO) formed by CALB showed that the copolymers contain
      nearly random sequences of PDL and DO units with a slight tendency toward
      alternating arrangements. Copolymerization with PDL was found to remarkably
      enhance PDO thermal stability. Differential scanning calorimetry (DSC) and wide
      angle X-ray scattering (WAXS) results demonstrate high crystallinity in all
      copolymers over the whole range of compositions. Depending on copolymer
      composition, the crystal lattice of either PDO or PPDL hosts units of the other
      comonomer, a behavior typical of an isodimorphic system. In poly(PDL-co-DO), both
      melting temperature and melting enthalpy display a minimum at 70 mol % DO, that
      is, at the pseudoeutectic composition. WAXS diffractograms show one crystal phase
      (that of either PPDL or PDO) on either side of the pseudoeutectic and coexistence
      of PPDL and PDO crystals at the pseudoeutectic.

PMID- 17550289
TI  - High-pressure potato starch granule gelatinization: synchrotron radiation micro
      SAXS/WAXS using a diamond anvil cell.
AB  - Potato starch granules have been examined by synchrotron radiation small- and
      wide-angle scattering in a diamond anvil cell (DAC) up to 750 MPa. Use of a 1
      microm synchrotron radiation beam allowed the mapping of individual granules at
      several pressure levels. The data collected at 183 MPa show an increase in the a
      axis and lamellar period from the edge to the center of the granule, probably due
      to a gradient in water content of the crystalline and amorphous lamellae. The
      average granules radius increases up to the onset of gelatinization at about 500
      MPa, but the a axis and the lamellar periodicity remain constant or even show a
      decrease, suggesting an initial hydration of amorphous growth rings. The onset of
      gelatinization is accompanied by (i) an increase in the average a axis and
      lamellar periodicity, (ii) the appearance of an equatorial SAXS streak, and (iii)
      additional short-range order peaks.

PMID- 17550290
TI  - New catalysts for Suzuki-Miyaura coupling reactions of heteroatom-substituted
      heteroaryl chlorides.
AB  - The new air-stable PdCl2[PR2(Ph-R')]2 complexes, readily prepared from commercial
      reagents, exhibit unique efficiency as catalysts for the Suzuki-Miyaura coupling
      reactions of a variety of heteroatom-substituted heteroaryl chlorides with a
      diverse range of aryl/heteroaryl boronic acids. The coupling reactions catalyzed
      by the new complexes exhibit high product yields (88-99%) and high catalyst
      turnover numbers (up to 10,000 TON).

PMID- 17550291
TI  - FeSO4 x 7H2O-catalyzed four-component synthesis of protected homoallylic amines.
AB  - An efficient catalytic four-component reaction of carbonyl compounds (or
      acetals/ketals), benzyl chloroformate (CbzCl), 1,1,1,3,3,3-hexamethyldisilazane
      (HMDS), and allyltrimethylsilane has been successfully developed to produce Cbz
      protected homoallylic amines in the presence of 5 mol % of iron(II) sulfate
      heptahydrate (FeSO4 x 7H2O), an inexpensive and environmentally friendly
      catalyst, at room temperature.

PMID- 17550292
TI  - Highly enantioselective conjugate addition of thiols using mild scandium triflate
      catalysis.
AB  - A Sc complex of (4S,5S)-diphenyl PYBOX 1 was found to serve as a catalyst for the
      asymmetric conjugate addition reactions between various thiols and 3-crotonoyl-2
      oxazolidinone, affording the corresponding adducts in good yields and high
      enantioselectivies (up to 92% ee). A new improved method for making (4S,5S)
      diphenyl PYBOX is presented.

PMID- 17550293
TI  - Effect of ring strain on nucleophilic substitution at selenium: a computational
      study of cyclic diselenides and selenenyl sulfides.
AB  - Nucleophilic substitution reactions of small rings incorporating selenium are
      examined using computational methods. The potential energy surfaces of HS- and
      HSe- with 1,2-diselenirane, 1,2-diselenetane, 1,2-diselenolane, and 1,2
      diselenane were computed at B3LYP/6-31+G(d) and MP2/6-31+G(d). The reactions of
      three-, four-, five-, and six-membered rings incorporating the S-Se bond with HS-
      were computed at B3LYP/6-31+G(d). The strained three- and four-membered
      diselenides and selenenyl sulfide rings undergo SN2 reactions, while the five-
      and six-membered rings react via the addition-elimination pathway, a path that
      invokes a hypercoordinate selenium intermediate. The strain in the small rings
      precludes the addition of a further ligand to either heteroatom. Substitution at
      selenium is both kinetically and thermodynamically favored over attack at sulfur.

PMID- 17550294
TI  - A convenient samarium-promoted synthesis of aliphatic (E)-nitroalkenes under mild
      conditions.
AB  - A samarium-promoted synthesis of (E)-nitroalkenes from 1-bromo-1-nitroalkan-2-ols
      in high yields and with total selectivity is reported. This reaction together
      with the easy and efficient preparation of the 1-bromo-1-nitroalkan-2-ols
      constitutes a simple and advantageous alternative toward nitroalkenes with total
      E-stereoselectivity. A mechanism is proposed to explain the E-stereoselectivity
      of the beta-elimination reaction.

PMID- 17550295
TI  - Rhodium- and iridium-catalyzed oxidative coupling of benzoic acids with alkynes
      via regioselective C-H bond cleavage.
AB  - The oxidative coupling of benzoic acids with internal alkynes effectively
      proceeds in the presence of [Cp*RhCl2]2 and Cu(OAc)2 x H2O as catalyst and
      oxidant, respectively, to produce the corresponding isocoumarin derivatives. The
      copper salt can be reduced to a catalytic quantity under air. Interestingly, by
      using [Cp*IrCl2]2 in place of [Cp*RhCl2]2, the substrates undergo 1:2 coupling
      accompanied by decarboxylation to afford naphthalene derivatives exclusively. In
      this case, Ag2CO3 acts as an effective oxidant.

PMID- 17550296
TI  - Enhanced parallel synthesis efficiency through tandem Pd-catalyzed S- and N
      arylation reactions: single-vessel formation of aminobenzothiazoles.

PMID- 17550297
TI  - Near-infrared resonant nanoshells for combined optical imaging and photothermal
      cancer therapy.
AB  - Metal nanoshells are core/shell nanoparticles that can be designed to either
      strongly absorb or scatter within the near-infrared (NIR) wavelength region (
      approximately 650-950 nm). Nanoshells were designed that possess both absorption
      and scattering properties in the NIR to provide optical contrast for improved
      diagnostic imaging and, at higher light intensity, rapid heating for photothermal
      therapy. Using these in a mouse model, we have demonstrated dramatic contrast
      enhancement for optical coherence tomography (OCT) and effective photothermal
      ablation of tumors.

PMID- 17550298
TI  - Controlled formation and mixing of two-dimensional fluids.
AB  - We introduce a novel technique for the controlled spreading and mixing of lipid
      monolayers from multilamellar precursors on surfaces covered by the hydrophobic
      epoxy resin SU-8. The lipid spreads as a monolayer as a result of the high
      surface tension between SU-8 and the aqueous environment. A micropatterned device
      with SU-8 lanes, injection pads, and mixing regions, surrounded by hydrophilic
      Au, was constructed to allow handling of lipid films and to achieve their mixing
      at controlled stoichiometry. Our findings offer a new approach to dynamic surface
      functionalization and decoration as well as surface-based catalysis and self
      assembly.

PMID- 17550300
TI  - The great failure of malaria control in Africa: a district perspective from
      Burkina Faso.

PMID- 17550301
TI  - Teaching global health at the frontlines. A multidisciplinary course in Peru
      presents basic concepts to students.

PMID- 17550302
TI  - Factors associated with findings of published trials of drug-drug comparisons:
      why some statins appear more efficacious than others.
AB  - BACKGROUND: Published pharmaceutical industry-sponsored trials are more likely
      than non-industry-sponsored trials to report results and conclusions that favor
      drug over placebo. Little is known about potential biases in drug-drug
      comparisons. This study examined associations between research funding source,
      study design characteristics aimed at reducing bias, and other factors that
      potentially influence results and conclusions in randomized controlled trials
      (RCTs) of statin-drug comparisons. METHODS AND FINDINGS: This is a cross
      sectional study of 192 published RCTs comparing a statin drug to another statin
      drug or non-statin drug. Data on concealment of allocation, selection bias,
      blinding, sample size, disclosed funding source, financial ties of authors,
      results for primary outcomes, and author conclusions were extracted by two coders
      (weighted kappa 0.80 to 0.97). Univariate and multivariate logistic regression
      identified associations between independent variables and favorable results and
      conclusions. Of the RCTs, 50% (95/192) were funded by industry, and 37% (70/192)
      did not disclose any funding source. Looking at the totality of available
      evidence, we found that almost all studies (98%, 189/192) used only surrogate
      outcome measures. Moreover, study design weaknesses common to published statin
      drug comparisons included inadequate blinding, lack of concealment of allocation,
      poor follow-up, and lack of intention-to-treat analyses. In multivariate analysis
      of the full sample, trials with adequate blinding were less likely to report
      results favoring the test drug, and sample size was associated with favorable
      conclusions when controlling for other factors. In multivariate analysis of
      industry-funded RCTs, funding from the test drug company was associated with
      results (odds ratio = 20.16 [95% confidence interval 4.37-92.98], p < 0.001) and
      conclusions (odds ratio = 34.55 [95% confidence interval 7.09-168.4], p < 0.001)
      that favor the test drug when controlling for other factors. Studies with
      adequate blinding were less likely to report statistically significant results
      favoring the test drug. CONCLUSIONS: RCTs of head-to-head comparisons of statins
      with other drugs are more likely to report results and conclusions favoring the
      sponsor's product compared to the comparator drug. This bias in drug-drug
      comparison trials should be considered when making decisions regarding drug
      choice.

PMID- 17550303
TI  - Vascular endothelial growth factor mediates intracrine survival in human breast
      carcinoma cells through internally expressed VEGFR1/FLT1.
AB  - BACKGROUND: While vascular endothelial growth factor (VEGF) expression in breast
      tumors has been correlated with a poor outcome in the pathogenesis of breast
      cancer, the expression, localization, and function of VEGF receptors VEGFR1 (also
      known as FLT1) and VEGFR2 (also known as KDR or FLK1), as well as neuropilin 1
      (NRP1), in breast cancer are controversial. METHODS AND FINDINGS: We investigated
      the expression and function of VEGF and VEGF receptors in breast cancer cells. We
      observed that VEGFR1 expression was abundant, VEGFR2 expression was low, and NRP1
      expression was variable. MDA-MB-231 and MCF-7 breast cancer cells, transfected
      with antisense VEGF cDNA or with siVEGF (VEGF-targeted small interfering RNA),
      showed a significant reduction in VEGF expression and increased apoptosis as
      compared to the control cells. Additionally, specifically targeted knockdown of
      VEGFR1 expression by siRNA (siVEGFR1) significantly decreased the survival of
      breast cancer cells through down-regulation of protein kinase B (AKT)
      phosphorylation, while targeted knockdown of VEGFR2 or NRP1 expression had no
      effect on the survival of these cancer cells. Since a VEGFR1-specific ligand,
      placenta growth factor (PGF), did not, as expected, inhibit the breast cancer
      cell apoptosis induced by siVEGF, and since VEGFR1 antibody also had no effects
      on the survival of these cells, we examined VEGFR1 localization. VEGFR1 was
      predominantly expressed internally in MDA-MB-231 and MCF-7 breast cancer cells.
      Specifically, VEGFR1 was found to be colocalized with lamin A/C and was expressed
      mainly in the nuclear envelope in breast cancer cell lines and primary breast
      cancer tumors. Breast cancer cells treated with siVEGFR1 showed significantly
      decreased VEGFR1 expression levels and a lack of VEGFR1 expression in the nuclear
      envelope. CONCLUSIONS: This study provides, to our knowledge for the first time,
      evidence of a unique survival system in breast cancer cells by which VEGF can act
      as an internal autocrine (intracrine) survival factor through its binding to
      VEGFR1. These results may lead to an improved strategy for tumor therapy based on
      the inhibition of angiogenesis.

PMID- 17550304
TI  - Principles of genome evolution in the Drosophila melanogaster species group.
AB  - That closely related species often differ by chromosomal inversions was
      discovered by Sturtevant and Plunkett in 1926. Our knowledge of how these
      inversions originate is still very limited, although a prevailing view is that
      they are facilitated by ectopic recombination events between inverted repetitive
      sequences. The availability of genome sequences of related species now allows us
      to study in detail the mechanisms that generate interspecific inversions. We have
      analyzed the breakpoint regions of the 29 inversions that differentiate the
      chromosomes of Drosophila melanogaster and two closely related species, D.
      simulans and D. yakuba, and reconstructed the molecular events that underlie
      their origin. Experimental and computational analysis revealed that the
      breakpoint regions of 59% of the inversions (17/29) are associated with inverted
      duplications of genes or other nonrepetitive sequences. In only two cases do we
      find evidence for inverted repetitive sequences in inversion breakpoints. We
      propose that the presence of inverted duplications associated with inversion
      breakpoint regions is the result of staggered breaks, either isochromatid or
      chromatid, and that this, rather than ectopic exchange between inverted
      repetitive sequences, is the prevalent mechanism for the generation of inversions
      in the melanogaster species group. Outgroup analysis also revealed evidence for
      widespread breakpoint recycling. Lastly, we have found that expression domains in
      D. melanogaster may be disrupted in D. yakuba, bringing into question their
      potential adaptive significance.

PMID- 17550305
TI  - Generation of active protein phosphatase 2A is coupled to holoenzyme assembly.
AB  - Protein phosphatase 2A (PP2A) is a prime example of the multisubunit architecture
      of protein serine/threonine phosphatases. Until substrate-specific PP2A
      holoenzymes assemble, a constitutively active, but nonspecific, catalytic C
      subunit would constitute a risk to the cell. While it has been assumed that the
      severe proliferation impairment of yeast lacking the structural PP2A subunit,
      TPD3, is due to the unrestricted activity of the C subunit, we recently obtained
      evidence for the existence of the C subunit in a low-activity conformation that
      requires the RRD/PTPA proteins for the switch into the active conformation. To
      study whether and how maturation of the C subunit is coupled with holoenzyme
      assembly, we analyzed PP2A biogenesis in yeast. Here we show that the generation
      of the catalytically active C subunit depends on the physical and functional
      interaction between RRD2 and the structural subunit, TPD3. The phenotype of the
      tpd3Delta strain is therefore caused by impaired, rather than increased, PP2A
      activity. TPD3/RRD2-dependent C subunit maturation is under the surveillance of
      the PP2A methylesterase, PPE1, which upon malfunction of PP2A biogenesis,
      prevents premature generation of the active C subunit and holoenzyme assembly by
      counteracting the untimely methylation of the C subunit. We propose a novel model
      of PP2A biogenesis in which a tightly controlled activation cascade protects
      cells from untargeted activity of the free catalytic PP2A subunit.

PMID- 17550306
TI  - Projected impacts of climate and land-use change on the global diversity of
      birds.
AB  - Over the past few decades, land-use and climate change have led to substantial
      range contractions and species extinctions. Even more dramatic changes to global
      land cover are projected for this century. We used the Millennium Ecosystem
      Assessment scenarios to evaluate the exposure of all 8,750 land bird species to
      projected land-cover changes due to climate and land-use change. For this first
      baseline assessment, we assumed stationary geographic ranges that may
      overestimate actual losses in geographic range. Even under environmentally benign
      scenarios, at least 400 species are projected to suffer >50% range reductions by
      the year 2050 (over 900 by the year 2100). Although expected climate change
      effects at high latitudes are significant, species most at risk are predominantly
      narrow-ranged and endemic to the tropics, where projected range contractions are
      driven by anthropogenic land conversions. Most of these species are currently not
      recognized as imperiled. The causes, magnitude and geographic patterns of
      potential range loss vary across socioeconomic scenarios, but all scenarios (even
      the most environmentally benign ones) result in large declines of many species.
      Whereas climate change will severely affect biodiversity, in the near future,
      land-use change in tropical countries may lead to yet greater species loss. A
      vastly expanded reserve network in the tropics, coupled with more ambitious goals
      to reduce climate change, will be needed to minimize global extinctions.

PMID- 17550307
TI  - Higher-order oligomerization targets plasma membrane proteins and HIV gag to
      exosomes.
AB  - Exosomes are secreted organelles that have the same topology as the cell and bud
      outward (outward is defined as away from the cytoplasm) from endosome membranes
      or endosome-like domains of plasma membrane. Here we describe an exosomal protein
      sorting pathway in Jurkat T cells that selects cargo proteins on the basis of
      both higher-order oligomerization (the oligomerization of oligomers) and plasma
      membrane association, acts on proteins seemingly without regard to their
      function, sequence, topology, or mechanism of membrane association, and appears
      to operate independently of class E vacuolar protein-sorting (VPS) function. We
      also show that higher-order oligomerization is sufficient to target plasma
      membrane proteins to HIV virus-like particles, that diverse Gag proteins possess
      exosomal-sorting information, and that higher-order oligomerization is a primary
      determinant of HIV Gag budding/exosomal sorting. In addition, we provide evidence
      that both the HIV late domain and class E VPS function promote HIV budding by
      unexpectedly complex, seemingly indirect mechanisms. These results support the
      hypothesis that HIV and other retroviruses are generated by a normal, nonviral
      pathway of exosome biogenesis.

PMID- 17550308
TI  - Evidence that a RecQ helicase slows senescence by resolving recombining
      telomeres.
AB  - RecQ helicases, including Saccharomyces cerevisiae Sgs1p and the human Werner
      syndrome protein, are important for telomere maintenance in cells lacking
      telomerase activity. How maintenance is accomplished is only partly understood,
      although there is evidence that RecQ helicases function in telomere replication
      and recombination. Here we use two-dimensional gel electrophoresis (2DGE) and
      telomere sequence analysis to explore why cells lacking telomerase and Sgs1p
      (tlc1 sgs1 mutants) senesce more rapidly than tlc1 mutants with functional Sgs1p.
      We find that apparent X-shaped structures accumulate at telomeres in senescing
      tlc1 sgs1 mutants in a RAD52- and RAD53-dependent fashion. The X-structures are
      neither Holliday junctions nor convergent replication forks, but instead may be
      recombination intermediates related to hemicatenanes. Direct sequencing of
      examples of telomere I-L in senescing cells reveals a reduced recombination
      frequency in tlc1 sgs1 compared with tlc1 mutants, indicating that Sgs1p is
      needed for tlc1 mutants to complete telomere recombination. The reduction in
      recombinants is most prominent at longer telomeres, consistent with a requirement
      for Sgs1p to generate viable progeny following telomere recombination. We
      therefore suggest that Sgs1p may be required for efficient resolution of telomere
      recombination intermediates, and that resolution failure contributes to the
      premature senescence of tlc1 sgs1 mutants.

PMID- 17550309
TI  - Histopathology of pneumothorax: potential diagnostic pitfalls.

PMID- 17550310
TI  - The burden of "sticky" amyloid: typing challenges.

PMID- 17550311
TI  - Clinical laboratory reports in molecular pathology.
AB  - CONTEXT: Molecular pathology is a rapidly growing area of laboratory medicine in
      which DNA and RNA are analyzed. The recent introduction of array technology has
      added another layer of complexity involving massive parallel analysis of multiple
      genes, transcripts, or proteins. OBJECTIVE: As molecular technologies are
      increasingly implemented in clinical settings, it is important to bring
      uniformity to the way that test results are reported. DATA SOURCES: The College
      of American Pathologists Molecular Pathology Resource Committee members summarize
      elements that are already common to virtually all molecular pathology reports, as
      set forth in the College of American Pathologists checklists used in the
      laboratory accreditation process. Consensus recommendations are proposed to
      improve report format and content, and areas of controversy are discussed.
      Resources are cited that promote use of proper gene nomenclature and that
      describe methods for reporting mutations, translocations, microsatellite
      instability, and other genetic alterations related to inherited disease, cancer,
      identity testing, microbiology, and pharmacogenetics. CONCLUSIONS: These
      resources and recommendations provide a framework for composing patient reports
      to convey molecular test results and their clinical significance to members of
      the health care team.

PMID- 17550313
TI  - Activated protein C resistance and factor V Leiden: a review.
AB  - CONTEXT: Factor V Leiden (FVL) is the most common heritable cause of venous
      thrombosis. It is caused by a single nucleotide substitution resulting in an
      R506Q missense mutation, resulting in factor V resistance to activated protein C
      (APC) inactivation. Carriers of FVL have an increased susceptibility to venous
      thrombosis, which is further increased in the presence of other genetic or
      environmental risk factors. OBJECTIVE: To review the biology, clinical findings,
      laboratory detection methods, and screening recommendations for patients with the
      FVL mutation. DATA SOURCES: PubMed review of published literature and online
      information. CONCLUSIONS: FVL remains an important heritable cause of
      hypercoagulability since its discovery more than 10 years ago. Clinical suspicion
      should be high in cases of unexplained venous thrombosis. APC resistance and FVL
      mutation can be diagnosed with high sensitivity and specificity with use of
      clotting time-based functional assays and genetic assays, respectively, allowing
      for evidence-guided clinical decision making regarding the benefit of long-term
      anticoagulation.

PMID- 17550314
TI  - Hyperhomocysteinemia and thrombosis: an overview.
AB  - CONTEXT: Homocysteine, a sulfur-containing amino acid, absent in natural diets,
      is a metabolic intermediary in transmethylation and transsulfuration reactions.
      Such reactions are essential to normal cellular growth, differentiation, and
      function. Excess homocysteine is associated with vascular disease and related
      disorders. OBJECTIVE: To review homocysteine metabolism, the pathogenesis and
      classification of hyperhomocysteinemia, and the published literature
      investigating the association of homocysteine and methylenetetrahydrofolate
      reductase defects with arterial and venous thromboembolism and related disorders.
      The role of vitamin supplementation in patients with hyperhomocysteinemia is
      addressed. DATA SOURCES: Published medical and scientific literature. Articles
      addressing the objectives were selected and reviewed. Pertinent studies and
      conclusions were summarized, grouped, and contrasted. CONCLUSIONS: The
      association of hyperhomocysteinemia and arterial and venous thrombosis is
      controversial. Severe hyperhomocysteinemia is associated with atherosclerosis.
      The effect of mild hyperhomocysteinemia is less certain. Coinheritance of
      methylenetetrahydrofolate reductase defects and factor V Leiden is likely to
      increase the risk of venous thromboembolism. The association of
      methylenetetrahydrofolate reductase defects combined with no additional
      thrombophilic risk factors with venous thrombosis is less clear. High doses of
      folic acid to lower homocysteine levels might not be necessary.

PMID- 17550315
TI  - Lupus anticoagulant assays: questions answered and to be answered.
AB  - CONTEXT: Lupus anticoagulants are antibodies with heterogenous specificities to
      phospholipids. They have been associated with clinical syndromes consisting of
      thrombosis and recurrent fetal loss. OBJECTIVE: To address questions about the
      laboratory assay aspects of lupus anticoagulants. This review is intended for
      clinicians managing lupus anticoagulant testing in clinical laboratories. DATA
      SOURCES: Published literature on lupus anticoagulants, with emphasis on
      laboratory assay methods. CONCLUSIONS: Although there are published criteria for
      confirming the presence of a lupus anticoagulant, there is no consensus on assay
      methods for lupus anticoagulant testing. The mixing study is a useful screening
      test for lupus anticoagulants, but it may have limited utility. Clinical context
      may necessitate the performance of factor assays in addition to lupus
      anticoagulant testing to rule out factor deficiency or factor-specific inhibitor.
      Additionally, the presence of different anticoagulants may affect the reliability
      of lupus anticoagulant assays. Lupus anticoagulants are an independent risk
      factor for thrombosis. It may be useful to use different assays when there is
      clinical suspicion for a lupus anticoagulant. When testing for lupus
      anticoagulants, clinicians must carefully consider the clinical context because
      factor assays may also be indicated.

PMID- 17550316
TI  - Hypercoagulation testing in ischemic stroke.
AB  - CONTEXT: The utility of laboratory testing for hypercoagulability in the setting
      of stroke is uncertain. OBJECTIVE: To review the current literature and to make
      recommendations with regard to laboratory testing for various hypercoagulability
      risk factors for ischemic stroke. DATA SOURCES: Published articles studying the
      utility of various hypercoagulation tests in predicting initial and/or recurrent
      stroke or transient ischemic attack as well as cerebral vein thrombosis were
      collected and reviewed, with an emphasis on prospective studies. CONCLUSIONS:
      Certain tests, such as C-reactive protein, homocysteine, antiphospholipid
      antibodies, and lipoprotein(a), may be useful in patients with a history of
      stroke or at high risk for stroke, as evidenced by prospective data. Factor V
      Leiden, prothrombin G20210A, protein C, protein S, and antithrombin are not
      recommended for routine testing but may be useful in certain populations, such as
      in pediatric patients or in patients with cerebral vein thrombosis.

PMID- 17550317
TI  - Reduced annexin II protein expression in high-grade prostatic intraepithelial
      neoplasia and prostate cancer.
AB  - CONTEXT: Annexin II is a calcium-dependent phospholipid-binding protein that
      plays a role in many cellular functions, including apoptosis, signal
      transduction, and cellular motility. The protein is strongly expressed in normal
      prostatic epithelial glands, but its expression in benign prostatic lesions has
      not been reported. Although commonly underexpressed in prostate cancer, the
      association of reduced expression with pathologic grade and stage is unknown.
      OBJECTIVE: To compare annexin II expression in benign prostatic lesions with
      expression in high-grade prostatic intraepithelial neoplasia and prostate cancer,
      as well as to correlate expression levels with pathologic grade and stage.
      DESIGN: A semi-quantitative assessment of annexin II expression was performed in
      radical prostatectomy specimens from 74 patients and prostate needle core biopsy
      specimens from 13 patients. Foci with normal prostatic glands, atrophic glands,
      basal cell hyperplasia, high-grade prostatic intraepithelial neoplasia, and
      prostatic adenocarcinoma were evaluated. RESULTS: Annexin II expression was
      present in more than 50% of glands in most (>85%) samples of benign prostatic
      epithelium, atrophic glands, and basal cell hyperplasia. In high-grade prostatic
      intraepithelial neoplasia, annexin II staining was markedly reduced in epithelial
      cells but not in basal cells. Annexin II was absent or focally present in
      moderately differentiated adenocarcinoma but was retained in poorly
      differentiated adenocarcinomas. CONCLUSIONS: Reduced annexin II expression may be
      a useful diagnostic biomarker to help identify small foci of moderately
      differentiated adenocarcinoma on needle core biopsy specimens since it is
      consistently expressed in benign prostatic glands. Re-expression of annexin II in
      poorly differentiated adenocarcinoma may provide prognostic information.

PMID- 17550318
TI  - Transfusion of platelets containing ABO-incompatible plasma: a survey of 3156
      North American laboratories.
AB  - CONTEXT: Hemolytic transfusion reactions due to platelet transfusions containing
      ABO-incompatible plasma (ie, group O platelets into a non-group O patient) have
      been reported in the literature. However, limited data describe the extent to
      which transfusion services manage such platelet transfusions or the methods used
      to limit the risk of such reactions. OBJECTIVE: To determine transfusion
      services' current practices regarding the use of platelets containing ABO
      incompatible plasma. DESIGN: In a College of American Pathologists' Transfusion
      Medicine Proficiency Testing Survey, supplemental questions asked participants
      whether a policy existed for the use of platelets containing ABO-incompatible
      plasma and, if a policy existed, what elements were part of the policy. RESULTS:
      Of 3156 laboratories that transfused platelets, 3152 responded to the question of
      whether they had a policy. Of these respondents, 83% (n = 2623) had a policy. One
      or more elements were reported for transfusions in adults: only ABO-compatible
      plasma products (n = 1363); only ABO-compatible plasma and platelet products (n =
      679); notification of medical director (n = 646); notification of ordering
      physician (n = 637); volume limit of ABO-incompatible plasma allowed (n = 255);
      volume-reduction of ABO-incompatible products (n = 168); screening for critical
      titer of anti-A or anti-B (n = 53). A total of 529 laboratories indicated that
      they did not have a policy. CONCLUSIONS: A majority of laboratories have a
      policy, but most do not include a method to limit the risk of hemolysis if
      platelets containing ABO-incompatible plasma must be transfused. When such
      platelets are used, there does not appear to be consensus on a specific method to
      minimize the transfusion of anti-A or anti-B.

PMID- 17550319
TI  - Typing of amyloidosis in renal biopsies: diagnostic pitfalls.
AB  - CONTEXT: Amyloidosis represents a group of diseases with extracellular deposition
      of congophilic fibrils of similar morphology but differing chemical composition.
      The types commonly involving the kidney are AL (light chain amyloid) and AA
      (serum amyloid A). Familial amyloidosis can also affect the kidney, but we have
      not encountered such a case during the study period. Distinguishing between the
      AL and AA forms of amyloid is clinically important because of the different
      treatments and outcomes. The classification of amyloidosis is made by
      immunostaining with antibodies to kappa and lambda immunoglobulin light chains
      and for serum amyloid A protein. OBJECTIVE: To draw attention to the nonspecific
      immunofluorescence staining patterns in renal biopsies with amyloidosis, causing
      potential diagnostic pitfalls. DESIGN: Renal biopsies from 15 patients, including
      13 cases of AL and 2 cases of AA amyloidosis, were studied. Immunofluorescence
      staining with routine antibody panel and immunoperoxidase staining for amyloid A
      were performed. RESULTS: Of the 13 cases of AL amyloidosis, 2 cases showed little
      difference in staining intensity between kappa and lambda light chains (2+ and
      3+, respectively) and 4 cases showed only moderate intensity (2+) of the
      predominant light chain. The 2 cases diagnosed as AA amyloidosis also exhibited
      staining for light chains. One case had strong (3+) signal for kappa and moderate
      (2+) for lambda light chain, while the other showed weaker staining. CONCLUSIONS:
      Immunofluorescence staining for immunoglobin light chains on renal biopsy, as the
      first step to differentiate between AL and AA amyloidosis, may sometimes be
      inconclusive or even misleading. Applying amyloid A immunostain on a routine
      basis and detailed clinical history are essential to avoid misclassification.

PMID- 17550320
TI  - Methylation profiles of multiple CpG island loci in extrahepatic
      cholangiocarcinoma versus those of intrahepatic cholangiocarcinomas.
AB  - CONTEXT: CpG island hypermethylation is attracting attention because of its
      importance as a tumor marker and its potential mechanism for the development of
      human cancers. Extrahepatic cholangiocarcinoma has been poorly investigated with
      respect to CpG island hypermethylation, and the number of genes known to be
      methylated in extrahepatic cholangiocarcinomas is fewer than 20. OBJECTIVE: To
      generate methylation profiles of 24 CpG island loci in extrahepatic
      cholangiocarcinomas, to correlate methylation findings with clinicopathologic
      findings, and to compare these findings with those of intrahepatic
      cholangiocarcinomas. DESIGN: Sixty-three extrahepatic cholangiocarcinomas and 48
      intrahepatic cholangiocarcinomas were investigated for hypermethylation in 24 CpG
      island loci by using methylation-specific polymerase chain reaction. RESULTS: A
      total of 61 (96.8%) of 63 extrahepatic cholangiocarcinomas showed
      hypermethylation in at least one of the examined loci, and a high methylation
      frequency was seen in HOXA1 (95.2%), HPP1 (69.8%), and NEUROG1 (61.9%). The
      number of methylated CpG island loci was greater in extrahepatic
      cholangiocarcinomas with nodal metastasis than in those without nodal metastasis
      (P = .047), and hypermethylation of TIG1 was closely associated with nodal
      metastasis of extrahepatic cholangiocarcinomas (P = .007). CDH1 and NEUROG1 were
      more frequently methylated in extrahepatic cholangiocarcinoma than in
      intrahepatic cholangiocarcinoma, whereas CHFR, GSTP1, IGF2, MGMT, MINT31, p14,
      and RBP1 were more frequently methylated in intrahepatic cholangiocarcinoma: the
      differences was statistically significant (P < .05). CONCLUSIONS: A close
      relationship exists between CpG island hypermethylation and nodal metastasis of
      extrahepatic cholangiocarcinomas. Methylation profiles of extrahepatic
      cholangiocarcinomas are somewhat similar to but distinct from those of
      intrahepatic cholangiocarcinomas.

PMID- 17550321
TI  - Type IV collagen immunostaining is a simple, reliable diagnostic tool for
      distinguishing between adenomatous and normal pituitary glands.
AB  - CONTEXT: Pituitary adenomas are clinically diagnosed based on radiologic studies
      and/or secondary effects of hormone production. Definitive pathologic
      identification relies on immunohistochemical detection of a clonal population of
      hormone-producing cells. However, not all adenomas secrete hormones, so
      performing a battery of stains is inefficient. Reports have shown decreased type
      IV collagen in the stroma of other epithelial tumors. OBJECTIVE: To validate type
      IV collagen immunohistochemistry as a diagnostic method. DESIGN: We immunostained
      27 adenomas and 19 normal pituitaries. The areas with the sparsest type IV
      collagen fibers were viewed at 3 magnifications (x10, x20, and x40 objectives),
      counting 1, 3, or 10 microscopic fields. A field was scored as "traversable" if a
      path existed from any point on the periphery of the field to a point on the
      approximately opposite periphery that did not cross any stained fibers. Results
      were compared with reticulin staining and to the existing diagnosis previously
      determined by histology, hormone immunostaining, and clinical correlation.
      RESULTS: Adenomas have less type IV collagen in their basement membranes, leading
      to sparser, trabecular staining in neoplasms versus a more rigid meshwork pattern
      in normal glands. One might envision the stained fibers as maze walls--one can
      traverse medium-powered fields in an adenoma, but one hits dead ends and gets
      trapped in those of a normal gland. Finding a single representative x10 field to
      be traversable was 97.5% sensitive and 96.5% specific for an adenoma. Reticulin
      staining yielded identical results. CONCLUSIONS: Type IV collagen immunostaining
      is a simple and reliable method of diagnosing pituitary adenomas.

PMID- 17550322
TI  - Promoter hypermethylation for molecular nodal staging in non-small cell lung
      cancer.
AB  - CONTEXT: Even among cases of non-small cell lung cancer (NSCLC) in the most
      favorable stage (IA), the disease-specific mortality is 25% or greater. One
      plausible explanation implicates the simplistic standard pathologic procedures
      used to designate lymph node involvement. A more sensitive assessment of the
      nodal status may improve staging. OBJECTIVE: To determine the prognostic impact
      of detecting an abnormal molecular event (promoter hypermethylation in a set of
      relevant genes) in histologically uninvolved lymph nodes in resected NSCLC.
      DESIGN: In this retrospective analysis of archived material, we examined DNA
      extracted from lymph nodes of stage I NSCLC (n = 180). Patients underwent surgery
      between 1991 and 1995 in a single institution. Methylation-specific polymerase
      chain reaction was used to detect promoter hypermethylation in a panel of 8
      genes. Survival data were extracted from the computerized database at the Tumor
      Registry. RESULTS: Evidence of promoter hypermethylation in at least 1 gene was
      detected in 67% of these N0 nodes. The most commonly hypermethylated gene was E
      cadherin (53%). The hypermethylation frequency for the remaining genes were as
      follows: APC, 5%; p16, 9%; MGMT, 11%; hMLH1, 15%; RASSF1A, 4%; DAP kinase, 9%;
      and ATM, 19%. The presence of promoter hypermethylation in 2 or more genes did
      not influence the overall, median, or 5-year survival rates. CONCLUSIONS:
      Identifying promoter hypermethylation (in our panel) in N0 lymph nodes in stage I
      NSCLC cannot be recommended for clinical decision making. Molecular
      abnormalities, including those found in cancer by qualitative methylation
      specific polymerase chain reaction, are not synonymous with established,
      histologically detectable metastasis.

PMID- 17550323
TI  - Sarcomas arising in Paget disease of bone: a clinicopathologic analysis of 70
      cases.
AB  - CONTEXT: Sarcomatous transformation is a rare complication of Paget disease of
      bone. Prognosis in patients with other types of sarcomas arising in bone has
      improved in the last several decades because of therapeutic advances. However,
      because of the rarity of Paget sarcoma, outcome studies in these patients are
      limited. OBJECTIVE: To determine whether prognosis for Paget sarcoma has
      improved. DESIGN: Seventy cases of sarcomas arising in the setting of Paget
      disease were collected, and the histologic and clinical findings were reviewed.
      Clinical follow-up was obtained in 67 cases. RESULTS: Sarcoma arising in Paget
      disease tended to arise in older men (46 men, 24 women; age range, 31-88 years;
      mean age, 66 years) and predominated in the axial skeleton (n = 37), especially
      in the pelvis. Thirty-three patients had a clinical history of Paget disease
      ranging in duration from 16 months to 30 years (mean, 15 years). No significant
      difference in incidence between monostotic (n = 33) and polyostotic (n = 36)
      disease was noted. Most tumors were osteosarcomas (88%). All tumors were high
      grade. Follow-up information was obtained in 67 of 70 cases (range of follow-up,
      1-252 months). Survival ranged from 1 month to 20 years, with a 5-year survival
      rate of 10%. CONCLUSIONS: Prognosis remains poor in patients with Paget sarcoma.
      There is no significant correlation between the number of bones involved with
      Paget disease or the duration of disease and development of Paget sarcoma. Poor
      prognosis in Paget sarcoma is unrelated to site or stage at presentation.

PMID- 17550324
TI  - Quantitative assessment of the BCR-ABL transcript using the Cepheid Xpert BCR-ABL
      Monitor assay.
AB  - CONTEXT: Chronic myelogenous leukemia (CML) and the assessment of the BCR-ABL
      transcript has become a new paradigm. Novel tyrosine kinase inhibitors as
      mainstream therapeutic options for the CML patient warrant routine quantification
      of the BCR-ABL transcript. The Xpert BCR-ABL Monitor assay is a nested reverse
      transcriptase polymerase chain reaction that greatly reduces technical time by
      using a single cartridge to isolate RNA and run a quantitative reverse
      transcriptase polymerase chain reaction. OBJECTIVE: To evaluate the Xpert BCR-ABL
      Monitor assay for quantitative assessment of the BCR-ABL transcript in CML
      patients. DESIGN: A standard curve of K-562 cells diluted in normal peripheral
      blood was used to test the sensitivity, linearity, and percent coefficient of
      variation of the assay. Specimen stability was tested by running standard curves
      immediately and after 24 hours or 96 hours of storage at 4 degrees C. Specimens
      from normal controls, patients known to have CML, or patients suspected of having
      CML were also tested. RESULTS: The sensitivity of the assay was sufficient to
      detect 1 K-562 cell in 10(5) normal cells. The R2 of the standard curve was 0.98
      and the percent coefficient of variation for each data point was 15% to 24%.
      Eleven of 14 patients with known CML on imatinib treatment tested positive for
      the BCR-ABL transcript, whereas 10 normal controls tested negative. CONCLUSIONS:
      The Xpert BCR-ABL Monitor assay is a rapid, sensitive method for monitoring the
      presence of the BCR-ABL transcript in CML patients. The single-use cartridge
      minimizes hands-on technical time, minimizes the potential for contamination, and
      allows quantitative BCR-ABL testing to be performed in a random access fashion.

PMID- 17550325
TI  - Quantitation of plasma cells in bone marrow aspirates by flow cytometric analysis
      compared with morphologic assessment.
AB  - CONTEXT: Accurate quantitation of bone marrow plasma cells is an important
      component in the diagnosis and posttreatment assessment of plasma cell
      dyscrasias. Although flow cytometry is sometimes used for this purpose and can
      rapidly evaluate many cells, the accuracy of flow-based plasma cell quantitation
      compared with morphologic assessment (currently the gold standard) is uncertain
      as direct comparison studies have not been previously reported. OBJECTIVE: To
      determine how percentages of plasma cells in diagnostic aspirate smears
      quantitated by morphologic assessment relate to percentages of plasma cells
      quantified by flow cytometry. DESIGN: Thirty bone marrow cases with 10% or more
      plasma cells and leukemia/lymphoma flow cytometry immunophenotyping studies were
      identified from our hematopathology database. The Wright-stained aspirate smears,
      marrow biopsy sections, and flow cytometry histograms were reviewed. RESULTS:
      Morphologically determined plasma cell percentages from the diagnostic aspirate
      smears were consistently higher than those determined by flow cytometry. Much of
      this difference appeared to be related to differences in sample quality. However,
      the cellular processing involved in performing flow cytometry also appeared to
      reduce plasma cell percentages in many cases. CONCLUSIONS: This study helps
      define the limitations of flow cytometry for quantitating plasma cell loads in
      marrow aspirate specimens that may significantly affect the diagnosis or
      assessment of treatment response.

PMID- 17550326
TI  - Relevance of parvovirus B19, herpes simplex virus 2, and cytomegalovirus
      virologic markers in maternal serum for diagnosis of unexplained recurrent
      abortions.
AB  - CONTEXT: The impact of viral infections during pregnancy on adverse pregnancy
      outcomes is not understood fully. OBJECTIVE: To assess the frequency of
      parvovirus B19, herpes simplex 2, and cytomegalovirus infections in relation to
      late abortions, in sera from Egyptian pregnant women to establish basic knowledge
      for future pregnancy care. In addition, to study the diagnostic value of specific
      immunoglobulin M (IgM) against those viruses compared with their genomes
      detection by polymerase chain reaction in maternal serum as a noninvasive method
      of laboratory diagnosis. DESIGN: Patients were recruited at the Women's Clinic,
      Mansoura University. One group of patients with recurrent spontaneous abortions
      (RSA) and a second group of pregnant women without a history of RSA were
      evaluated including demographic, medical, and clinical data. Virologic markers
      were evaluated for specific IgM and for viral DNA to cytomegalovirus, herpes
      simplex virus 2, and parvovirus B19. RESULTS: There was a statistically
      significant difference between the RSA group and the pregnant women without RSA
      group in frequency of parvovirus IgM (84% and 16.7%, respectively) (P < .001) and
      herpes simplex IgM (40% for RSA) (P = .001). Parvovirus B19 viremia was positive
      in 48% RSA, herpes simplex virus 2 was positive in 32% RSA, and cytomegalovirus
      was positive in 12% RSA patients. For RSA patients with parvovirus viremia, the
      mean +/- SD of IgM value was 78.5 +/- 30.12 IU/mL, and for RSA patients with
      negative viremia it was 30.02 +/- 17.64 IU/mL with statistically significant
      difference between both levels (P < .001). CONCLUSIONS: From this study, we
      conclude that viral infections with parvovirus B19 and herpes simplex 2 were
      frequently associated with recurrent abortions, and careful investigation for
      this condition must include evaluating these patients for the previously
      mentioned viruses. Serologic study by specific IgM for parvovirus and herpes
      simplex seem to be reliable as screening tests for high-risk pregnancy.

PMID- 17550327
TI  - Signet-ring cell adenocarcinoma of sinonasal tract: an immunohistochemical study
      of the mucins profile.
AB  - CONTEXT: Adenocarcinomas of the sinonasal tract are classified into 4 categories:
      salivary-type, intestinal-type, nonintestinal-type, and metastatic. Signet-ring
      cell carcinoma is the rarest form of intestinal-type adenocarcinoma. Only
      isolated cases have been reported in the literature. OBJECTIVE: To evaluate
      clinical attributes, morphology, and immunohistochemistry in signet-ring cell
      carcinoma of the sinonasal tract. DESIGN: Seventy-three cases of primary
      sinonasal adenocarcinomas were retrieved from the files. Only 5 signet-ring cell
      adenocarcinomas (tumors composed of more than 90% signet-ring cells) were
      identified. In all cases, clinical data and histologic slides were available and
      were reviewed. Consecutive tissue sections were immunostained with monoclonal
      antibodies against MUC2, MUC5AC, MUC5B, MUC6, p53 protein, and MIB-1. RESULTS:
      Four of our 5 patients were woodworkers. They were treated by surgical excision
      and radiotherapy. Patient follow-up ranged from 11 to 84 months. Three patients
      presented an unfavorable evolution and died of metastatic spread.
      Microscopically, the tumors produced abundant mucin deposits, which accumulated
      in large extracellular pools. Tumor cells were predominantly signet-ring cells
      floating in the pools of mucin. The mucins profile was MUC2+, MUC5AC+, MUC5B+,
      and MUC6-. Eighty percent of cells were immunostained by p53 protein antibody and
      60% cells with MIB-1 antibody. CONCLUSIONS: The mucin profile is similar to the
      profile described in digestive tract adenocarcinoma. It is not useful to
      differentiate between metastatic adenocarcinoma and primary intestinal-type
      sinonasal adenocarcinoma. Clinical data and immunochemistry with p53 protein and
      MIB-1 confirm that sinonasal signet-ring cell carcinoma is a high-grade and
      aggressive tumor.

PMID- 17550328
TI  - Splenic metastases: clinicopathologic presentation, differential diagnosis, and
      pathogenesis.
AB  - CONTEXT: Splenic metastases from solid tumors, defined as parenchymal lesion, are
      considered exceptional. Nevertheless, the number of case reports has been
      increasing due to the improvement of imaging techniques and the long-term follow
      up of patients with cancer. Splenic metastases occur in a context of
      multivisceral disseminated cancer or as a solitary lesion. OBJECTIVE: To provide
      a general overview of the clinicopathologic features, differential diagnosis, and
      pathogenesis of splenic metastases. DATA SOURCES: Relevant articles indexed in
      PubMed (National Library of Medicine) database. The search was based on the
      following terms: (metastasis or metastases) and spleen. CONCLUSIONS: The most
      common primary sources of splenic metastasis are breast, lung, colorectal, and
      ovarian carcinomas and melanoma in cases of multivisceral cancer and colorectal
      and ovarian carcinomas in cases of solitary splenic lesion. Splenectomy can be
      replaced by less aggressive methods such as fine-needle aspiration or
      percutaneous biopsy for establishing the diagnosis of solitary splenic
      metastasis. The main differential diagnoses are primary lymphoma, vascular
      tumors, and infectious lesions of the spleen. The relative rarity of splenic
      metastases could be explained by anatomic factors and the inhibitory effect of
      the splenic microenvironment on the growth of metastatic cells. The analysis of
      clinical case reports suggests that solitary splenic metastases may result from
      the growth of an early blood-borne micrometastasis following a period of clinical
      latency, often several years after the diagnosis of the primary tumor.

PMID- 17550329
TI  - Occult primary parotid gland acinic cell adenocarcinoma presenting with extensive
      lung metastasis.
AB  - Acinic cell adenocarcinoma is a malignant salivary gland neoplasm with a
      relatively low rate of lymphangitic spread to regional lymph nodes. Distant
      metastases are rare and their occurrence typically indicates an unfavorable
      outcome. We encountered an unusual example of acinic cell adenocarcinoma that
      initially presented in the lung, whereas the primary parotid carcinoma, despite
      extensive clinical evaluation, only became apparent 1 year after initial
      diagnosis. The histologic, immunohistochemical, and ultrastructural features of
      the tumor in the parotid gland and lung were similar. The tumor displayed an
      aggressive behavior resulting in death within 2 years of the initial
      presentation. This presentation is unique, showing that peripheral lung tumors of
      salivary gland type are likely to be metastatic, and careful clinical evaluation
      is warranted in establishing their primary site of origin.

PMID- 17550330
TI  - Sclerosing angiomatoid nodular transformation of the spleen.
AB  - Sclerosing angiomatoid nodular transformation (SANT) is a recently recognized
      nonneoplastic vascular lesion of the spleen with fewer than 30 cases described.
      Microscopically, SANT consists of multiple well-circumscribed
      vascular/angiomatoid nodules showing plump endothelial cell and extravasated
      erythrocytes. The nodules are surrounded by a variable lymphoplasmacytic
      infiltrate, spindle cells, and collagenous stroma. The vascular nodules display a
      complex mixture of endothelial phenotypes resembling splenic sinusoids (CD34
      /CD31+/CD8+), capillaries (CD34+/ CD31+/CD8-), and small veins (CD34-/CD31+/CD8
      ). Focal expression of CD68 can also be seen. The differential diagnosis of SANT
      includes splenic hamartoma, inflammatory myofibroblastic tumor, littoral cell
      angioma, and hemangioendothelioma. It has been postulated that SANT represents a
      peculiar hamartomatous transformation of splenic red pulp in response to an
      exaggerated nonneoplastic stromal proliferation. SANT has a benign clinical
      course with splenectomy being curative.

PMID- 17550331
TI  - Sertoliform endometrioid carcinoma of the ovary: a potential diagnostic pitfall.
AB  - Sertoliform endometrioid carcinoma of the ovary (SEC) is an uncommon variant that
      bears histologic similarity to Sertoli and Sertoli-Leydig cell tumors (SLTs).
      Clinically, SEC affects an older population (60-70 years), while patients with
      SLT have an average age of 25 years and may exhibit endocrine manifestations. A
      number of histologic features can be used to distinguish the 2 entities, the most
      important ones being (1) the presence of areas with the usual pattern of
      endometrioid carcinoma, and (2) the presence of mucin at the apical borders of
      the tumor cells. Cytokeratin stains positively, while inhibin and calretinin
      stain negatively in SEC; the converse is true for SLTs. Based on the
      clinicopathologic behavior of this entity, SEC should be considered a well
      differentiated carcinoma with relatively good prognosis if limited to the ovary.

PMID- 17550332
TI  - Hansen disease in the United States in the 21st century: a review of the
      literature.
AB  - In this article we review the recent literature on Hansen disease (leprosy). We
      searched published literature through PubMed (National Library of Medicine) and
      extracted data through direct review of the literature and pathologic slides.
      Hansen disease continues to occur in the United States, including among the
      native-born population. Inclusion of the disease in the differential diagnosis is
      key to confirmation. Current epidemiology, classification systems, prevention
      measures, and therapy are reviewed.

PMID- 17550334
TI  - Evaluating Australian Indigenous community health promotion initiatives: a
      selective review.
AB  - Effective health promotion interventions are critical to addressing the health
      needs of Indigenous people. We reviewed published and unpublished evaluation
      reports between 2000 and 2005 to identify practice issues pertinent to evaluators
      of Aboriginal and Torres Strait Islander health promotion initiatives. While the
      review of the literature was not systematic it was sufficiently comprehensive to
      provide a snapshot of evaluation practice currently in place within the
      Australian context. We found that published evaluation literature infrequently
      referred to the utilisation of guidelines for ethical research with Aboriginal
      and Torres Strait Islander peoples. The implications of this are that the
      importance and relevance of the guidelines for evaluative research are not being
      widely promoted or disseminated to evaluation practitioners and the role of the
      guidelines for improving evaluation practice remain unclear. While many
      innovative health promotion programs appear to have been highly regarded and well
      received by communities, the evaluation studies were not always able to report
      conclusively on the impact and health outcomes of these interventions or
      programs. This was due mainly to limitations in evaluation design that in some
      cases were insufficiently robust to measure the complex and multifaceted
      interventions described. To enhance rigour, evaluators of community health
      promotion initiatives could utilise mixed method approaches overtly informed by
      appropriate ethical guidelines, together with a broader range of qualitative
      methods aided by critical appraisal tools to assist in the design of evaluation
      studies.

PMID- 17550335
TI  - Caveolin-1 knockout mice have increased bone size and stiffness.
AB  - The skeletal phenotype of the cav-1(-/-) mouse, which lacks caveolae, was
      examined. muCT and histology showed increased trabecular and cortical bone caused
      by the gene deletion. Structural changes were accompanied by increased mechanical
      properties. Cell studies showed that cav-1 deficiency leads to increased
      osteoblast differentiation. These results suggest that cav-1 helps to maintain
      osteoblast progenitors in a less differentiated state. INTRODUCTION: The absence
      of caveolin-1 in cellular membranes causes dysregulated signaling. To understand
      the role of the caveolar microdomain in bone homeostasis, we examined the
      skeletal phenotype of 5- and 8-wk-old cav-1(-/-) mice. MATERIALS AND METHODS:
      High-resolution microCT imaging showed a region-specific effect of cav-1
      deficiency on the skeleton. At 5 wk, cav-1(-/-) mice had increased epiphyseal
      bone volume (+58.4%, p = 0.05); at 8 wk, metaphyseal bone volume was increased by
      77.4% (p = 0.008). Cortical bone at the femoral mid-diaphysis showed that the
      periosteal area of cav-1(-/-) mice significantly exceeded that of cav-1(+/+) mice
      by 23.9% and 16.3% at 5 and 8 wk, respectively, resulting in increased mechanical
      properties (I(max): +38.2%, p = 0.003 and I(mi): +23.7%, p = 0.03). RESULTS:
      Histomorphometry complemented microCT results showing increased bone formation
      rate (BFR) at trabecular and cortical sites at 5 wk, which supported findings of
      increased bone at 8 wk in cav-1(-/-) mice. Formal mechanical testing of the
      femoral diaphysis confirmed increased bone structure: stiffness increased 33% and
      postyield deflection decreased 33%. Stromal cells from cav-1(-/-) marrow showed a
      23% increase in von Kossa-positive nodules; osteoclastogenesis was also modestly
      increased in cav-1-deficient marrow. Knockdown of cav-1 with siRNA in wildtype
      stromal cells increased alkaline phosphatase protein and expression of osterix
      and Runx2, consistent with osteoblast differentiation. CONCLUSIONS: These data
      suggest that cav-1 helps to maintain a less differentiated state of osteoblast
      progenitor cells, and the absence of cav-1 causes bone to mature more rapidly.
      Caveolin-1 may thus be a target for altering skeletal homeostasis.

PMID- 17550336
TI  - Herpes simplex virus VP22 enhances adenovirus-mediated microdystrophin gene
      transfer to skeletal muscles in dystrophin-deficient (mdx) mice.
AB  - One of the obstacles to efficient vector-mediated gene therapy for Duchenne's
      muscular dystrophy (DMD) is its limited transduction efficiency. The VP22
      tegument protein of herpes simplex virus type 1 (HSV-1) is able to cross
      biological membranes and translocate the VP22 fusion protein from transfected
      primary cells to surrounding cells and improve the outcome of gene transfer. To
      improve the efficiency of vector-mediated gene therapy and to investigate the
      utility of the intercellular trafficking properties of VP22-linked protein for
      the treatment for DMD, the recombinant adenoviruses Ad-VP22, Ad-MICDYS, and Ad
      VP22-MICDYS were constructed and the VP22-mediated shuttle effect was evaluated
      both in vitro and in vivo. About 92 +/- 3.6% of cells were microdystrophin
      positive 48 hr postinfection with Ad-VP22-MICDYS. The number of centralized
      nuclei in Ad-VP22-MICDYS-transduced tibialis anterior (TA) muscle was
      significantly reduced, from 78 +/- 5.2 to 20 +/- 2.5%, by 2 weeks postinjection.
      By 2 months postinjection, the average number of microdystrophin-positive fibers
      in TA muscle injected with Ad-VP22-MICDYS was 2.2 times more than that of TA
      muscle injected with Ad-MICDYS. Ad-VP22-MICDYS led to significant recovery of
      force-producing capabilities in TA muscle. These results demonstrate that VP22
      greatly augmented adenovirus-mediated microdystrophin delivery to C2C12 cells and
      to the skeletal muscles of dystrophin-deficient (mdx) mice. These results
      highlight the efficiency of VP22-mediated intercellular protein delivery for the
      potential therapy of DMD and suggest that VP22 may be a promising tool with which
      to enhance the efficacy of adenoviral gene transfer for somatic gene therapy of
      DMD.

PMID- 17550337
TI  - Commentary: engineering of tissue healing and regeneration.
AB  - Regenerative medicine aims to restore homeostasis of diseased tissues and organs.
      With time, engineered replacement tissue constructs will play an increasingly
      important role in achieving this goal. Equally important, however, will be the
      ability to resolve disease-associated inflammation and to optimize tissue
      regenerative capacity by specifically patterning the host tissue
      microenvironment. The tools of bioengineering are uniquely suited to meet these
      challenges. Here, the candidate molecular and cellular targets for manipulating
      the host's inflammatory environment and tissue regenerative capacity are briefly
      discussed within the context of current and emerging bioengineering strategies.
      The objective is to draw the attention of basic scientists and engineers to the
      importance of regulating inflammation in achieving the goals of tissue
      engineering and regenerative medicine.

PMID- 17550338
TI  - In vitro angiogenesis properties of endothelial progenitor cells: a promising
      tool for vascularization of ex vivo engineered tissues.
AB  - Survival of ex vivo constructed tissues after transplantation is limited by
      insufficient oxygen and nutrient supply. Therefore, strategies aiming at the
      improvement of neovascularization of engineered tissues are a key issue. A method
      to enhance graft vascularization is to establish a primitive vascular plexus
      within the graft before transplantation by the use of cellular-based concepts. To
      explore the utility of endothelial progenitor cells (EPCs) for the ex vivo
      vascularization of tissue engineered grafts, we analyzed the in vitro angiogenic
      properties of this cell type in two different angiogenesis models: the 3
      dimensional spheroid sprouting assay and the 2-dimensional matrigel assay. In
      both assays, EPCs were able to form tubelike structures, resembling early
      capillaries. This process was significantly enhanced by the addition of
      angiogenic growth factors. Direct comparison between EPCs and mature endothelial
      cells, represented by human umbilical vein endothelial cells (HUVECs), revealed
      that both cell types displayed an almost identical angiogenic potential. Other
      functional in vitro parameters such as angiogenic growth factor induced cell
      proliferation and cell survival were investigated as well, revealing a
      significantly decreased level of apoptosis of EPCs in relation to HUVECs under
      serum-deprived conditions. The observed survival advantage of EPCs along with the
      observation that EPCs perform very well in the above mentioned in vitro
      angiogenesis assays, make them an ideal autologous cell source for
      vascularization of ex vivo generated tissues. The attractiveness of this cell
      type for tissue engineering applications is strengthened further by the fact that
      these cells can be easily isolated from the peripheral blood of patients, thereby
      eliminating donor site morbidity.

PMID- 17550339
TI  - Stem/Progenitor cell sources of insulin-producing cells for the treatment of
      diabetes.
AB  - Patients with diabetes experience decreased insulin secretion that is linked to a
      significant reduction in the number of islet cells. Reversal of diabetes can be
      achieved through islet transplantation, but the scarcity of donor islets severely
      hinders wide application of this therapeutic modality. Toward that end, embryonic
      stem cells, adult tissue-residing progenitor cells, and regenerating native beta
      cells may serve as sources of islet cell surrogates. Insulin-producing cells
      generated from stem or progenitor cells display subsets of native beta-cell
      attributes, indicating the need for further development of methods for
      differentiation to completely functional beta-cells. Pharmacological approaches
      aiming at stimulating the in vivo/ex vivo regeneration of beta-cells have also
      been proposed as a way of augmenting islet cell mass. We review the current state
      of the generation of insulin-producing cells from different sources with emphasis
      on embryonic stem cells and adult progenitor cells. Challenges for the clinical
      use of these sources are also discussed.

PMID- 17550341
TI  - The uneasy ethical and legal underpinnings of large-scale genomic biobanks.
AB  - Abstract Large-scale genomic databases are becoming increasingly common. These
      databases, and the underlying biobanks, pose several substantial legal and
      ethical problems. Neither the usual methods for protecting subject
      confidentiality, nor even anonymity, are likely to protect subjects' identities
      in richly detailed databases. Indeed, in these settings, anonymity is itself
      ethically suspect. New methods of consent will need to be created to replace the
      blanket consent common to such endeavors, with a consent procedure that gives
      subjects some real control over what they might consider inappropriate use of
      their information and biological material. Through their use, these biobanks are
      also likely to yield information that will be of some clinical significance to
      the subjects, information that they should have access to. Failure to adjust to
      these new challenges is not only legally and ethically inappropriate, but puts at
      risk the political support on which biomedical research depends.

PMID- 17550342
TI  - Function of the zinc-finger transcription factor SNAI2 in cancer and development.
AB  - Elucidation of the molecular mechanisms that underlie disease development is
      still a tremendous challenge for basic science, and a prerequisite to the
      development of new and disease-specific targeted therapies. This review focuses
      on the function of SNAI2, a member of the Snail family of zinc-finger
      transcription factors, and discusses its possible role in disease development.
      SNAI2 has been implicated in diseases of melanocyte development and cancer in
      humans. Many malignancies arise from a rare population of cells that alone have
      the ability to self-renew and sustain the tumor (i.e., cancer stem cells). SNAI2
      controls key aspects of stem cell function in mouse and human, suggesting that
      similar mechanisms control normal development and cancer stem cell properties.
      These insights are expected to contribute significantly to the genetics of cancer
      and to the development of both cancer therapy and new methods for assessing
      treatment efficacy.

PMID- 17550343
TI  - Putting the altruism back into altruism: the evolution of empathy.
AB  - Evolutionary theory postulates that altruistic behavior evolved for the return
      benefits it bears the performer. For return-benefits to play a motivational role,
      however, they need to be experienced by the organism. Motivational analyses
      should restrict themselves, therefore, to the altruistic impulse and its knowable
      consequences. Empathy is an ideal candidate mechanism to underlie so-called
      directed altruism, i.e., altruism in response to anothers's pain, need, or
      distress. Evidence is accumulating that this mechanism is phylogenetically
      ancient, probably as old as mammals and birds. Perception of the emotional state
      of another automatically activates shared representations causing a matching
      emotional state in the observer. With increasing cognition, state-matching
      evolved into more complex forms, including concern for the other and perspective
      taking. Empathy-induced altruism derives its strength from the emotional stake it
      offers the self in the other's welfare. The dynamics of the empathy mechanism
      agree with predictions from kin selection and reciprocal altruism theory.

PMID- 17550344
TI  - A comprehensive review of the placebo effect: recent advances and current
      thought.
AB  - Our understanding and conceptualization of the placebo effect has shifted in
      emphasis from a focus on the inert content of a physical placebo agent to the
      overall simulation of a therapeutic intervention. Research has identified many
      types of placebo responses driven by different mechanisms depending on the
      particular context wherein the placebo is given. Some placebo responses, such as
      analgesia, are initiated and maintained by expectations of symptom change and
      changes in motivation/emotions. Placebo factors have neurobiological
      underpinnings and actual effects on the brain and body. They are not just
      response biases. Other placebo responses result from less conscious processes,
      such as classical conditioning in the case of immune, hormonal, and respiratory
      functions. The demonstration of the involvement of placebo mechanisms in clinical
      trials and routine clinical practice has highlighted interesting considerations
      for clinical trial design and opened up opportunities for ethical enhancement of
      these mechanisms in clinical practice.

PMID- 17550345
TI  - Resveratrol is a class IA phosphoinositide 3-kinase inhibitor.
AB  - Resveratrol, a polyphenol found in fruits, possesses chemopreventive and
      chemotherapeutic properties and has been shown to increase lifespan in yeast and
      metazoans, including mice. Genetic evidence and in vitro enzymatic measurements
      indicate that the deacetylase Sir2/SIRT1, an enzyme promoting stress resistance
      and aging, is the target of resveratrol. Similarly, down-regulation of insulin
      like pathways, of which PI3K (phosphoinositide 3-kinase) is a key mediator,
      promotes longevity and is an attractive strategy to fight cancer. We show here
      that resveratrol inhibits, in vitro and in cultured muscle cell lines, class IA
      PI3K and its downstream signalling at the same concentration range at which it
      activates sirtuins. Our observations define class IA PI3K as a target of
      resveratrol that may contribute to the longevity-promoting and anticancer
      properties and identify resveratrol as a natural class-specific PI3K inhibitor.

PMID- 17550346
TI  - The PCSK9 gene R46L variant is associated with lower plasma lipid levels and
      cardiovascular risk in healthy U.K. men.
AB  - In the present study, we have determined the relative frequency of the R46L,
      I474V and E670G variants in the PCSK9 (protein convertase subtilisin/kexin type
      9) gene and its association with plasma lipid levels and CHD (coronary heart
      disease) in healthy U.K. men and patients with clinically defined definite FH
      (familial hypercholesterolaemia). Genotypes were determined using PCR and
      restriction enzyme digestion in 2444 healthy middle-aged (50-61 years) men from
      the prospective NPHSII (Second Northwick Park Heart Study), with 275 CHD events
      (15 years of follow-up), and in 597 U.K. FH patients from the Simon Broome
      Register. In the NPHSII healthy men, the R46L genotype distribution was in Hardy
      Weinberg equilibrium and the frequency of 46L was 0.010 [95% CI (confidence
      interval), 0.007-0.013], with one man homozygous for the 46L allele. There was
      significant association of the 46L allele with lower mean (S.D.) total
      cholesterol [5.74 (1.01) mmol/l for RR compared with 5.26+/-1.03 mmol/l for RL;
      P=0.001], apolipoprotein B [0.87 (0.24) g/l for RR compared with 0.75 (0.26) g/l
      for RL; P<0.0001] and low-density lipoprotein cholesterol [4.01 (0.95) mmol/l for
      RR compared with 3.62 (0.97) mmol/l for RL; P=0.02]) levels, after adjustment for
      age, general medical practice, smoking, body mass index and systolic blood
      pressure. As expected, 46L carriers had a low risk of definite or possible CHD
      [hazard ratio, 0.46 (95% CI, 0.11-1.84)], but this was not statistically
      significant (P=0.27). Two other common PCSK9 variants I474V [V allele frequency,
      0.179 (95% CI, 0.17-0.19)] and E670G [G allele frequency, 0.034 (CI, 0.03-0.04)]
      were not associated with any significant effects on lipid levels or CHD risk. In
      FH patients, the frequency of 46L was 0.003 (95% CI, 0.00-0.01), which was
      significantly lower (P=0.037) than the healthy subjects. In the four FH patients
      carrying 46L, mean untreated total cholesterol levels were not different (P=0.91)
      in carriers and non-carriers (median, 10.3 mmol/l compared with 10.2 mmol/l
      respectively, after adjustment for age, gender and mutation type). In conclusion,
      the PCSK9 46L allele is more frequent in healthy U.K. men than in FH patients and
      is strongly associated with a protective plasma lipid profile risk for CHD. Its
      low frequency (approx. 2% carriers) means that it does not make a major
      contribution to determining population CHD risk in the U.K.

PMID- 17550348
TI  - Assessment of orthostatic fluid shifts with strain gauge plethysmography.
AB  - We evaluated the use of strain gauge plethysmography (SGP) for the assessment of
      orthostatic fluid shifts during head up tilt (HUT). Subjects wore a parachute
      harness fixed to the tilt table to avoid muscle tension in the lower limbs during
      HUT. 22 Healthy subjects (9 women) were tilted for 5 minutes. Calf volume changes
      as measured by SGP, surface EMG, heart rate and blood pressure were measured
      continuously. Ten subjects underwent a second tilt test during which circulation
      in one leg was occluded with a pressure cuff at 250 mmHg. During HUT with
      occlusion, calf volume increased in the non-occluded leg by 1.9+/-0.3% (mean +/-
      SEM) and 0.2+/-0.2% in the occluded leg (p<0.001). During HUT without occlusion a
      significant correlation (r = 0.9) was found between measurements of the left and
      right leg with a mean difference of 0.03+/-0.1%. HUT did not cause significant
      changes of surface EMG. An unexpected gender effect was found: calf volume
      increased significantly more in men than in women. Men were significantly taller,
      but the hemodynamic response to HUT did not differ between both sexes. The gender
      effect on orthostatic increases of calf volume remained significant after
      adjustment for heart-to-calf distance. SGP during HUT with a parachute harness is
      a new, promising method to assess orthostatic fluid shifts. The gender
      differences in orthostatic pooling in the calf may be explained by a higher calf
      compliance in men together with a greater hydrostatic pressure due to a greater
      height in men.

PMID- 17550347
TI  - Western diet, but not high fat diet, causes derangements of fatty acid metabolism
      and contractile dysfunction in the heart of Wistar rats.
AB  - Obesity and diabetes are associated with increased fatty acid availability in
      excess of muscle fatty acid oxidation capacity. This mismatch is implicated in
      the pathogenesis of cardiac contractile dysfunction and also in the development
      of skeletal-muscle insulin resistance. We tested the hypothesis that 'Western'
      and high fat diets differentially cause maladaptation of cardiac- and skeletal
      muscle fatty acid oxidation, resulting in cardiac contractile dysfunction. Wistar
      rats were fed on low fat, 'Western' or high fat (10, 45 or 60% calories from fat
      respectively) diet for acute (1 day to 1 week), short (4-8 weeks), intermediate
      (16-24 weeks) or long (32-48 weeks) term. Oleate oxidation in heart muscle ex
      vivo increased with high fat diet at all time points investigated. In contrast,
      cardiac oleate oxidation increased with Western diet in the acute, short and
      intermediate term, but not in the long term. Consistent with fatty acid oxidation
      maladaptation, cardiac power decreased with long-term Western diet only. In
      contrast, soleus muscle oleate oxidation (ex vivo) increased only in the acute
      and short term with either Western or high fat feeding. Fatty acid-responsive
      genes, including PDHK4 (pyruvate dehydrogenase kinase 4) and CTE1 (cytosolic
      thioesterase 1), increased in heart and soleus muscle to a greater extent with
      feeding a high fat diet compared with a Western diet. In conclusion, we implicate
      inadequate induction of a cassette of fatty acid-responsive genes, and impaired
      activation of fatty acid oxidation, in the development of cardiac dysfunction
      with Western diet.

PMID- 17550349
TI  - Animal breeding and the black box of biology.

PMID- 17550350
TI  - Variance components due to direct genetic, maternal genetic and permanent
      environmental effect for growth and feed-efficiency traits in young male Japanese
      Black cattle.
AB  - Variance components and genetic parameters were estimated using data recorded on
      740 young male Japanese Black cattle during the period from 1971 to 2003. Traits
      studied were feed intake (FI), feed-conversion ratio (FCR), residual feed intake
      (RFI), average daily gain (ADG), metabolic body weight (MWT) at the mid-point of
      the test period and body weight (BWT) at the finish of the test (345 days). Data
      were analysed using three alternative animal models (direct, direct + maternal
      environmental, and direct + maternal genetic effects). Comparison of the log
      likelihood values has shown that the direct genetic effect was significant (p <
      0.05) for all traits and that the maternal environmental effects were significant
      (p < 0.05) for MWT and BWT. The heritability estimates were 0.20 +/- 0.12 for FI,
      0.14 +/- 0.10 for FCR, 0.33 +/- 0.14 for RFI, 0.19 +/- 0.12 for ADG, 0.30 +/-
      0.14 for MWT and 0.30 +/- 0.13 for BWT. The maternal effects (maternal genetic
      and maternal environmental) were not important in feed-efficiency traits. The
      genetic correlation between RFI and ADG was stronger than the corresponding
      correlation between FCR and ADG. These results provide evidence that RFI should
      be included for genetic improvement in feed efficiency in Japanese Black breeding
      programmes.

PMID- 17550351
TI  - Genetic parameters for feed efficiency traits and their relationships with growth
      and carcass traits in Duroc pigs.
AB  - Genetic parameters for feed efficiency traits of 380 boars and growth and carcass
      traits of 1642 pigs (380 boars, 868 gilts and 394 barrows) in seven generations
      of Duroc population were estimated. Feed efficiency traits included the feed
      conversion ratio (FCR), and nutritional (RFI(nut)), phenotypic (RFI(phe)) and
      genetic (RFI(gen)) residual feed intake. Growth and carcass traits were the age
      to reach 105-kg body weight (A105), loin eye muscle area (EMA), backfat (BF),
      intra-muscular fat (IMF) and meat tenderness. The mean values for RFI(phe) and
      RFI(gen) were close to zero and for RFI(nut) was negative. All the measures of
      feed efficiency were moderately heritable (h(2) = 0.31, 0.38, 0.40 and 0.27 for
      RFI(nut), RFI(phe), RFI(gen) and FCR respectively). The heritabilities for all
      growth and carcass traits were moderate (ranged from 0.37 to 0.45), except for
      BF, which was high (0.72). The genetic correlations of RFI(phe) and RFI(gen) with
      A105 were positive and high. Measures of RFI were correlated negatively with EMA.
      BF was more strongly correlated with measures of RFI (r(g) > or = 0.73) than with
      FCR (r(g) = 0.52). Selection for daily gain, EMA, BF and IMF caused favourable
      genetic changes in feed efficiency traits. Results of this study indicate that
      selection against either RFI(phe) or RFI(gen) would give a similar correlated
      response in carcass traits.

PMID- 17550352
TI  - Genetic analysis of racing performance in Irish greyhounds.
AB  - The aim of this study was to analyse racing performance data in Irish greyhounds
      with regard to genetic and environmental variation. Estimation of heritabilities
      for racing time (RT) and ranking, and the prediction of breeding values for all
      greyhounds in the investigated data were carried out. Data from 42,785 races in
      Ireland in the years 2000-2003 were available. These results were obtained from
      42,880 greyhounds on 20 race tracks over a distance of 480 m. Three traits were
      analysed, RT, ranking and a scaled logarithmic function for RT (ART), which was
      used to adjust racing time to be normally distributed. The data were analysed
      with a bivariate animal model. The estimated heritabilities were moderate for RT
      (0.31) and ART (0.38), but very low for ranking (0.10). The repeatabilities were
      0.56 (RT), 0.51 (ART) and 0.13 (ranking). The genetic correlations were very
      high, 0.99 (RT-ranking) and 0.96 (ART-ranking), while the phenotypic correlation
      was lower, 0.60 (RT-ranking) and 0.62 (ART-ranking). The genetic trend for the
      traits as well as the phenotypic change of the average RT was positive.

PMID- 17550353
TI  - Possibility of selecting racehorses on jumping ability based on their
      steeplechase race results in France, the United Kingdom and Ireland.
AB  - The aim of this study was to detect Thoroughbred mare families and sire lines, in
      France, in the United Kingdom and Ireland, whose offspring may be successful in
      steeplechase races and can be recommended therefore for sport horse breeding.
      Race results were collected from all steeplechase races in these countries
      between 1998 and 2003, which contained the results of 17,355 horses from 12,861
      dams and 2452 sires. In France, non-Thoroughbred horses were also included in the
      analysis because they race and mate together with Thoroughbreds. Performance was
      measured with two criteria: earnings and ranks after mathematical transformation.
      The effects of year, sex, age and race were considered as fixed, animal,
      permanent environment and maternal environment as random. Precorrection for the
      effect of race was done to avoid computational difficulties. Maternal
      environmental components for ranks were 0.02 in France and zero in the United
      Kingdom and Ireland. Estimated heritabilities for the ranking criteria were 0.18
      (repeatability 0.33) in France and 0.06 (repeatability 0.19) in the United
      Kingdom and Ireland. The high genetic correlation between the two criteria of
      measurement (0.94 and 0.97 respectively) gives the opportunity to choose the most
      suitable criteria for breeding value estimation. The ranking value, after
      statistical normalization has a great advantage for comparison between the
      countries.

PMID- 17550354
TI  - Characterization of the porcine insulin-like growth factor-binding protein, acid
      labile subunit gene: full-length cDNA and DNA sequence, polymorphisms and
      expression profile.
AB  - Insulin-like growth factor-binding protein acid-labile subunit (IGFALS) is an
      important glycoprotein in the circulation complex for insulin-like growth factors
      I and -II (IGFs). So far only a partial porcine IGFALS sequence is available. We
      herein report the isolation, characterization, polymorphism identification and
      expression analysis of the porcine IGFALS gene. A 2000-bp full-length cDNA
      sequence was determined with 5'- and 3'-Rapid Amplification of cDNA End (RACE)
      assay. It contains a 1821-bp open reading frame encoding a protein of 606 amino
      acids with a calculated molecular mass of 66 kDa and a theoretical isoelectric
      point of 6.89. The deduced IGFALS protein shares high identity (70-80%) with
      other mammalian IGFALS. We also obtained a full-length genomic DNA sequence of
      the gene. Similar to the other mammalian orthologues, particularly in terms of
      exon size and exon/intron boundaries, the porcine IGFALS gene spans a
      transcription unit of 2990 bp, consisting of two exons and one intron. Three
      single nucleotide polymorphisms (synonymous mutations) were identified in the DNA
      sequence. RT-PCR assays indicate that IGFALS is expressed ubiquitously in pigs
      and transcripts are particularly abundant in the liver, lung, white adipose
      tissue, prostate, epididymis, thyroid and bladder.

PMID- 17550355
TI  - SNP discovery, expression and association analysis for the SDHD gene in pigs.
AB  - The SDHD gene was examined for single nucleotide polymorphisms (SNP) as well as
      for expression changes in the Longissimus dorsi muscle of commercial pigs with
      different potential for growth. Three SNPs, including one previously described in
      the coding region and two new ones in the 3'-UTR, were found. The normalized
      expression of SDHD was correlated with growth, meat quality and sensory traits (p
      < 0.05). For the commercial pigs used in this study, as well as a Berkshire x
      Yorkshire resource population, the SNPs have been associated (p < 0.05) with:
      growth, carcass composition, meat quality and sensory traits. Despite the fact
      that the described SNPs were not significantly associated with the normalized
      expression values, the SDHD SNPs and expression were associated with growth and
      meat quality traits in pigs.

PMID- 17550356
TI  - Identification of mutations of zona pellucida glycoprotein (ZP3) and its
      association with pig reproductive traits.
AB  - Reproduction is a complex trait, controlled by genetic and environmental factors.
      Genetic improvement of this trait is important for animal breeders to improve the
      animal's production efficiency. Apart from genetic factors, animal production can
      be affected by environmental factors, i.e. the nursing ability of the sow, which
      is in turn affected directly by effective teat number (teats producing milk
      normally, TN) and number of piglets born alive (NBA). The objective of this study
      was to find new mutations, such as single nucleotide polymorphisms (SNPs) from
      the Zona Pellucida glycoprotein gene (ZP3) using Single Strand Chain Polymorphism
      (SSCP) and nucleotide sequencing and to investigate association between genetic
      variations and sow reproductive traits. We identified 13 new SNPs from exon 1,
      two new SNPs from intron 2, one SNP from intron 6 and a 18 bp (GCACGTGGTCCTCCTGG)
      deletion/insertion from intron 2 of the ZP3 gene. Five out of these mutations
      were selected to genotype in five different breeds (Small Meishan, Qingping,
      Duroc, Landrace and Large White) and association with reproductive traits in
      European breeds (Duroc, Landrace and Large White). The sows with genotype AA had
      more 1.11 piglets NBA than of the sows with genotype AB (p < 0.05) in the 18 bp
      deletion/insertion of intron 2, while non-significant associations between the
      other mutations and reproductive traits (NBA and TN) were found.

PMID- 17550357
TI  - The polymorphism in the beta4-defensin gene and its association with production
      and somatic cell count in Holstein-Friesian cows.
AB  - The aim of this study was to find a polymorphism of the bovine beta4-defensin
      gene and search for its association with milk yield and composition and with the
      somatic cell count in milk. The data were from the years 1999 to 2004 on 212
      Holstein-Friesian (HF) dairy cows, descended from 70 sires. Based on the sequence
      of the bovine beta4-defensin gene (GenBank no. AF008307) the primers were
      designed for the amplification of the 924-bp or 393-bp long fragments. The 924-bp
      long fragment was sequenced and the sequence was compared with that available in
      the GenBank. Ten putative nucleotide sequence polymorphisms were found in the
      intron of the bovine beta4-defensin gene. One of them, a C-->T transition at
      position 2239, that creates a new NlaIII (Hin1II) restriction site, was genotyped
      with polymerase chain reaction-restriction fragment length polymorphism (PCR
      RFLP) in a cohort of 212 HF cows. The CC genotype was the most common (72%). The
      heterozygous CT genotype was found in 26% of the genotyped cows and four cows
      (2%) were TT homozygotes. In order to determine the relationship between the
      polymorphism of the beta4-defensin gene and milk production traits a multi-trait
      repeatability test-day animal model was used. The Derivative-free Multivariate
      analysis program was used for computation. The differences between estimates for
      genotypes were checked using Student's t-test. The model included the animal
      genotype, year-season of calving and parity as fixed effects and the animal
      additive genetic effect and permanent environmental effect of individual cows as
      well as dates of the tests as random effects. Significant associations were found
      between the RFLP-NlaIII and milk fat, protein and lactose contents. Also, a
      significant effect was shown of the defensin genotype on the somatic cell count
      in the milk.

PMID- 17550358
TI  - Effect of polymorphisms linked to LEP gene on its expression on adipose tissues
      in beef cattle.
AB  - In cattle, genetic markers at the leptin (LEP) gene and at those linked to the
      gene have been described as affecting calving interval (markers LEPSau3AI and
      IDVGA51), or daily weight gain (BMS1074 and BM1500). This work investigated the
      effect of these alleles on LEP mRNA levels in cattle subcutaneous and omental
      adipose tissues. A sample of 137 females of a Brangus-Ibage beef cattle herd was
      analysed to evaluate the distribution of the polymorphisms; then, animals having
      at least one of the IDVGA51*181 (allele 181 at marker IDVGA51; six animals),
      LEPSau3AI*2 (four), BMS1074*151 (13), BM1500*135 (six) alleles and a control
      group composed of animals without any of these alleles (four animals) were
      submitted to surgery to obtain omental and subcutaneous adipose tissues. Leptin
      mRNA expression was quantified by TaqMan RT-PCR, using 18S rRNA as internal
      control and adjusted for the effect of body condition score, through regression
      analysis. Omental fat had LEP gene expression 33% lower than the subcutaneous
      tissue. Carriers of IDVGA*181 and BMS1074*151 showed subcutaneous fat leptin mRNA
      levels higher than the controls. Leptin controls feed intake and coordinates
      reproduction; therefore, animals with higher LEP gene expression will probably
      have lower daily weight gain than others with similar forage offer and
      nutritional condition and probably will also have longer calving interval.

PMID- 17550359
TI  - The mechanisms determining the nucleolar-organizing regions inactivation of
      domestic horse chromosomes.
AB  - Cytogenetic investigations of the nucleolar-organizing regions (NORs) show that
      there is variation in the transcriptional activity of rDNA in many organisms. As
      a consequence, genetic polymorphism of these regions has been detected. The aim
      of the present study was to evaluate the hypothetic genetic mechanisms
      determining the NORs polymorphism of the domestic horse chromosomes. Molecular
      cytogenetic analyses were carried out on Hucul horses and the following
      techniques were used: fluorescence in situ hybridization (FISH), telomere primed
      in situ synthesis (PRINS), in situ nick-translation with HpaII, silver staining
      (AgNOR) and C-banding technique (CBG). The obtained results suggest that
      variation in the number and size of silver deposits is related to the number of
      rDNA copies, DNA methylation and the localization of ribosomal DNA loci in
      telomeric regions. Moreover, we have found that chromosome pairs 28 and 31 are
      characterized by higher variation in the NORs number.

PMID- 17550360
TI  - Fluorescent in situ hybridization mapping of the epidermal growth factor receptor
      gene in donkey.
AB  - The physical localization of the epidermal growth factor receptor (EGFR) gene was
      performed on donkey chromosomes. Bacterial artificial chromosome DNA containing
      the equine EGFR gene was used to map this gene by fluorescent in situ
      hybridization on donkey metaphase chromosomes. The gene was mapped on donkey
      1q21.1 region.

PMID- 17550361
TI  - Long-term effects of brief substance use interventions for mandated college
      students: sleeper effects of an in-person personal feedback intervention.
AB  - BACKGROUND: It is known that brief interventions for mandated college students
      decrease alcohol use and/or related problems in the short term. However, none of
      the existing studies has followed students' past 6 months. Therefore, we compared
      the long-term efficacy of 2 brief substance use feedback interventions for
      mandated college students. METHODS: We followed up mandated students (N=348) who
      were randomly assigned to either a brief motivational interview (BMI; n=180) or a
      written feedback-only (WF; n=168) intervention at 4 months and 15 months
      postintervention. RESULTS: Long-term follow-up data revealed that students, at
      the aggregate level, decreased their peak blood alcohol concentration (BAC)
      levels, number of drinks per week, and number of alcohol-related problems at 15
      months postintervention compared with their baseline levels. With the exception
      of peak BAC, the observed long-term reduction was mainly due to the positive
      change among students who received the BMI intervention. Students in the BMI
      intervention showed significantly lower levels of alcohol-related problems at 15
      months than those in the WF intervention. The BMI intervention more effectively
      reduced within-individual alcohol-related problems during the initial 4 months,
      and more successfully curbed the subsequent increase in alcohol use frequency and
      number of drinks per week during the 11 months between the 2 follow-up
      assessments. CONCLUSIONS: The results suggest that brief substance use
      interventions reduce the riskiest type of alcohol use (e.g., peak BAC) among
      mandated college students over the long term, and that sleeper effects of in
      person personal feedback interventions (PFIs) exist. In-person PFIs in the
      context of a motivational interview may be more efficacious in the long term than
      written feedback-only interventions for mandated students. Future studies
      comparing interventions for college students should extend follow-up for longer
      periods of time.

PMID- 17550362
TI  - Effects of a moderate evening alcohol dose. II: performance.
AB  - BACKGROUND: This second of a pair of papers investigates the effects of a
      moderate dose of alcohol and staying up late on driving simulation performance
      and simple visual reaction time (RT) at a known circadian phase in well-rested
      young adults. METHODS: Twenty-nine adults (9 males), ages 21 to 25 years, spent 1
      week on an at-home stabilization schedule of 8.5 to 9 hours, followed by 3
      nonconsecutive nights in-lab: adaptation, placebo, and alcohol. Performance task
      practice occurred on 3 occasions before the study. Alcohol (vodka; 0.54 g/kg men;
      0.49 g/kg women mixed with tonic) was consumed over 30 minutes ending 1 hour
      before normal bedtime; the same quantity of beverage was given on placebo.
      Driving simulation (with drive-only and dual-task drive and subtract components)
      and psychomotor vigilance task (PVT) testing occurred before and after
      alcohol/placebo ingestion. Breath alcohol concentration (BrAC) readings were
      taken before all test sessions. Saliva samples were taken approximately every 30
      minutes to determine circadian phase. RESULTS: Driving simulation and PVT
      variables significantly deteriorated with increasing time awake. Driving
      simulator lane variability was worse with alcohol compared with placebo at 15.5
      hours awake. No PVT variable showed an effect of alcohol. CONCLUSIONS: Driving
      simulation performance deteriorated with extended waking and with alcohol;
      driving was most impaired at the peak alcohol level. The PVT, less complex than
      the driving simulation, did not show effects of alcohol, a finding consistent
      with previous literature that disruptive effects of low alcohol concentrations
      increase with task complexity. Overall, simulated driving performance is
      significantly impaired late at night when even a moderate dose of alcohol is
      consumed.

PMID- 17550363
TI  - Effects of a moderate evening alcohol dose. I: sleepiness.
AB  - BACKGROUND: Few studies examining alcohol's effects consider prior sleep/wake
      history and circadian timing. We examined introspective and physiological
      sleepiness on nights with and without moderate alcohol consumption in well-rested
      young adults at a known circadian phase. METHODS: Twenty-nine adults (males=9),
      ages 21 to 25 years (M=22.6, SD=1.2), spent 1 week on an at-home stabilized sleep
      schedule (8.5 or 9 hours), followed by 3 in-lab nights: adaptation, placebo, and
      alcohol. Alcohol (vodka; 0.54 g/kg for men; 0.49 g/kg for women) or placebo
      beverage was consumed over 30 minutes ending 1 hour before stabilized bedtime. In
      addition to baseline, 3 sleep latency tests (SLTs) occurred after alcohol/placebo
      ingestion (15, 16.5, and 18 hours after waking). Stanford Sleepiness Scales (SSS)
      and Visual Analog Scales (VAS) of sleepiness were completed before each SLT and
      approximately every 30 minutes. The Biphasic Alcohol Effects Scale (BAES) was
      administered a total of 4 times (baseline, 5, 60, and 90 minutes
      postalcohol/placebo). Subjects' circadian phase was determined from melatonin
      levels in saliva samples taken at approximately 30-minute intervals. RESULTS: All
      sleepiness and sedation measures increased with time awake. Only SSS and BAES
      sedation measures showed higher levels of sleepiness and sedation after alcohol
      compared with placebo. The mean circadian phase was the same for assessments at
      both conditions. CONCLUSIONS: Alcohol did not increase physiological sleepiness
      compared with placebo nor was residual sedation evident under these conditions.
      We conclude that the effects on sleepiness of a moderate dose of alcohol are
      masked when sleep-wake homeostatic and circadian timing influences promote high
      levels of sleepiness.

PMID- 17550364
TI  - Effects of selective opioid receptor antagonists on alcohol-induced and nicotine
      induced antinociception.
AB  - BACKGROUND: Despite synergistic increases in risks of various cancers, the
      incidence of concomitant smoking and drinking remains high. An additive or
      synergistic analgesic effect of combined alcohol and nicotine may contribute to
      their coabuse. Recently, we provided evidence that doses of alcohol and nicotine
      that are ineffective in inducing an antinociceptive effect alone, when combined,
      can induce such an effect. Moreover, this antinociceptive effect could be
      attenuated by pretreatment with the nonselective opioid antagonist naloxone. The
      purpose of this study was to determine the role of selective opioid receptor
      subtypes (micro, delta, and kappa) in mediating the antinociceptive effects of
      alcohol, nicotine, and their combination. METHODS: Adult male Wistar rats were
      administered selective opioid antagonists, D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr
      NH(2) (CTAP, for micro receptor, 1.0 mg/kg), naltrindole (for delta receptors, 10
      mg/kg), and norbinaltorphimine (nor-BNI, for kappa receptor, 10 mg/kg) before
      injection of alcohol, nicotine or their combination. The animals were tested in
      hot-plate and tail-flick assays, representing nociception mediated predominantly
      via brain or spinal pathways, respectively. All the injections were administered
      acutely and the nociceptive tests were carried out 20 minutes after alcohol and
      10 minutes after nicotine administration. RESULTS: In general, the antagonists
      were more effective in blocking the effects of alcohol, nicotine, or their
      combination in the tail-flick versus the hot-plate assay. CTAP was most effective
      in blocking the effects of alcohol alone and nicotine alone in the tail-flick
      test, whereas in the hot-plate test both CTAP and naltrindole were more effective
      than nor-BNI. All 3 antagonists had a very similar profile in attenuating the
      combination of alcohol and nicotine effect in the hot-plate assay. None of the
      antagonists had a significant effect against the highest alcohol-nicotine dose in
      this test. In the tail-flick test, however, CTAP and naltrindole were more
      effective than nor-BNI in attenuating the highest alcohol-nicotine dose.
      CONCLUSIONS: The data suggest the utility of all 3 opioid antagonists in blocking
      the effects of alcohol, nicotine, or their combination in spinally mediated
      antinociception. Although the supraspinally mediated antinociception was also
      attenuated by the opioid antagonists, further investigation of combination doses
      of these antagonists in fully blocking the supraspinal effects or attenuating
      voluntary alcohol and nicotine intake is warranted.

PMID- 17550365
TI  - Socio-cognitive habilitation using the math interactive learning experience
      program for alcohol-affected children.
AB  - BACKGROUND: Fetal alcohol syndrome (FAS) has been recognized as a disabling
      condition with a significant impact on the neurobehavioral functioning of
      affected individuals, including cognition, behavior, and academic functioning,
      but little research has been performed on targeted interventions for these
      children. METHODS: A socio-cognitive habilitative program focused on improving
      behavior and math functioning in children 3 to 10 years of age (n=61) was
      developed and evaluated. The intervention provided parental instruction on FAS,
      advocacy, and behavioral regulation via workshops and interactive math tutoring
      with children. All families received parental instruction and were then randomly
      assigned to either the math instruction or standard psychoeducational care
      groups. RESULTS: Satisfaction with workshops was very high, with over 90%
      agreeing that trainers were knowledgeable and materials easy to understand and
      helpful. Significant gains in knowledge were found for information provided in
      the instructional groups. At posttesting, caregivers reported fewer problem
      behaviors on the Achenbach Child Behavior Checklist, Internalizing Problem
      Behavior, Externalizing Problem Behavior, and Total Problem Behavior summary
      scales. After 5 months, both groups of children demonstrated gains in math
      knowledge but significantly higher gains were found in the group receiving direct
      math instruction. The math treatment group was also more likely to demonstrate a
      gain of over 1 standard deviation on any of the 4 math outcome measures used.
      CONCLUSIONS: These findings suggest that parents of children with fetal alcohol
      spectrum disorders (FAS(D)) benefit from instruction in understanding their
      child's alcohol-related neurological damage and strategies to provide positive
      behavioral supports and that targeted psychoeducational programs may be able to
      remediate some of the math deficits associated with prenatal alcohol exposure.

PMID- 17550366
TI  - Randomized-controlled trial of a telephone and mail intervention for alcohol use
      disorders: three-month drinking outcomes.
AB  - BACKGROUND: Alcohol screening, brief intervention, and referral to specialized
      treatment (ASBIR) reduce drinking and related harms. Unanswered questions are how
      to manage nondependent patients with poor response to brief interventions, how to
      manage dependent patients who do not obtain treatment, and how to ensure
      population-wide delivery of ASBIR. Telephone-administered counseling may provide
      answers. METHODS: We conducted a 12-month randomized controlled trial of a
      telephone and mail intervention for non-treatment-seeking primary care patients
      with alcohol use disorders. We enrolled 897 subjects after systematic screening
      in 18 primary care clinic waiting rooms in and around Madison and Milwaukee,
      Wisconsin, and subsequent telephone-administered diagnostic interviews.
      Experimental subjects received up to six sessions of protocol-driven telephone
      counseling based on principles of motivational interviewing and stages of
      readiness to change. Control subjects received a pamphlet on healthy lifestyles.
      The paper reports on 3-month drinking outcomes for men and women with alcohol
      abuse and dependence. RESULTS: Male experimental subjects (N=199) manifested a
      30.6% decline in risky drinking days, compared with a 8.3% decline in controls
      (N=201, p<0.001). The total consumption declined by 17.3% compared with 12.9% by
      controls (p=0.001). Female experimental subjects (N=246) manifested a 17.2%
      decrease in risky drinking days compared with an 11.5% decrease by controls
      (N=251; p=NS) and a 13.9% decline in total consumption compared with 11.0% by
      controls (p=NS). Greater numbers of telephone counseling sessions were associated
      with greater declines in drinking. CONCLUSION: Following systematic screening, a
      six-session telephone and mail intervention is more effective than a pamphlet in
      reducing drinking at 3 months for non-treatment-seeking men with alcohol abuse
      and dependence. An intervention effect of the enrollment procedures may have
      obscured further intervention effectiveness. Telephone counseling shows promise
      for non-treatment-seeking primary care patients with alcohol use disorders.

PMID- 17550367
TI  - Avoidance of alcohol-related stimuli in alcohol-dependent inpatients.
AB  - BACKGROUND: Previous research has shown an attentional bias toward drug-related
      stimuli in heavy social drinkers. Attentional orientation to drug-related cues
      may lead to increased craving and preoccupation with the drug and impaired
      ability to focus attention on nondrug-related activities, resulting in renewed
      drug taking or relapse from drug abstinence. OBJECTIVE: The aim of this study was
      to investigate whether alcohol-dependent inpatients would differ in their
      selective attention toward alcohol-related stimuli in comparison with a group of
      social drinking controls. METHOD: Thirty-five alcohol-dependent inpatients were
      compared with a group of 39 social drinking controls matched for age, sex, and
      verbal IQ. Attentional bias was assessed using alcohol-related pictures in a dot
      probe detection task. Questionnaires were used to examine outcome expectancies
      after alcohol consumption, anxiety, mood, and craving. RESULTS: The alcoholic
      inpatients showed a bias away from the alcohol-related stimuli, scored higher on
      alcohol outcome expectancies, and on anxiety measures (both state and trait).
      They also presented with more negative mood compared with the control group.
      Craving was higher in the alcoholic group for the factor "loss of control over
      drinking." CONCLUSIONS: Alcoholic inpatients undergoing treatment based on the 12
      step treatment of Alcoholics Anonymous (Minnesota model), which includes
      counseling, and intensive group, individual, and family psychotherapy, show an
      avoidance for drug-related stimuli and a perception of loss of control over
      drinking. We suggest that their increased perception of loss of control over
      drinking produces the avoidance from the drug-related stimuli.

PMID- 17550368
TI  - Matching law choice analyses of ethanol and sucrose consumption in alcohol
      preferring (P), nonpreferring (NP), and Sprague-Dawley (SD) rats.
AB  - BACKGROUND: Quantitative models of choice, such as the matching law and
      behavioral economics, allow for the analysis of alcohol consumption within a
      choice context. Such models can provide further knowledge of phenotypic
      differences between selected lines of rats. The current study applied the
      generalized matching law to the ethanol (EtOH) and sucrose consumption of alcohol
      preferring (P), nonpreferring (NP), and Sprague-Dawley (SD) rats. METHODS: Male
      P, NP, and SD rats were trained to consume increasing concentrations of EtOH and
      water in a limited access, 2-bottle choice procedure. The animals were then given
      concurrent access to pairs of differing EtOH solutions (2, 4, 6, and 10%, v/v)
      for 1 h/d. A subset of animals from each rat type was subsequently given access
      to 8% sucrose for 1 h/d for 5 days, and then concurrent access to pairs of
      differing sucrose solutions (3, 8, and 15%, w/v) for 1 h/d. The generalized
      matching law was used to assess the relationship between the relative EtOH and
      sucrose concentrations and the relative volumes of solutions consumed. RESULTS:
      The P rats consumed more EtOH and sucrose than the NP and SD rats overall.
      However, only the P rats consistently consumed disproportionately greater
      quantities of the higher EtOH concentration than the lower one, indicating
      overmatching. Additionally, all 3 types of rats displayed overmatching in the
      sucrose choice experiment. CONCLUSIONS: These data provide further evidence of
      phenotypic differences between the P rats and other types of rats, and suggest
      that the generalized matching law can be a useful tool for describing rats' EtOH
      or sucrose consumption in a 2-bottle choice, limited access paradigm.

PMID- 17550369
TI  - Alcohol drinking in MCH receptor-1-deficient mice.
AB  - BACKGROUND: Recently, we demonstrated that exogenous melanin-concentrating
      hormone (MCH) increases alcohol drinking in rats when administered into the
      brain. However, because the physiological relevance of this finding is unclear,
      we tested the hypothesis that endogenous MCH signaling enhances alcohol
      consumption. METHODS: Alcohol intake was assessed in male and female wildtype
      (WT), heterozygous (HET), and homozygous MCH receptor-1-deficient (KO) mice. Mice
      were given 24-hour access to a series of alcohol-containing solutions. Following
      this, the mice were given limited (1-hour) access to 10% alcohol. Finally, mice
      were allowed 24-hour access to sucrose/quinine as a caloric control and a means
      to assess taste preference. A naive cohort of male WT and KO mice was tested for
      alcohol clearance following intraperitoneal administration of 3 g/kg alcohol.
      Another naive cohort of female mice was utilized to confirm that
      intracerebroventricular administration of MCH (5 microg) would augment alcohol
      drinking in mice. RESULTS: Exogenous MCH enhanced 10% alcohol consumption in mice
      (saline=0.45+/-0.08 g/kg, 5 microg MCH=0.94+/-0.20 g/kg). Male KO mice consumed
      more 10% alcohol (11.50+/-1.31 g/kg) than WT (6.26+/-1.23 g/kg) and HET mice
      (6.49+/-1.23 g/kg) during ad libitum access. However, alcohol intake was similar
      among genotypes during 1 hour daily access. Male KO mice tended to consume less
      17.75% sucrose+1.3 mM quinine than controls (WT=10.5+/-3.6, HET=7.5+/-1.7,
      KO=4.4+/-0.9 g/kg). Alcohol metabolism was similar between WT and KO mice.
      CONCLUSIONS: The finding that male KO consume more alcohol than WT and HET mice,
      are reminiscent of the counterintuitive reports that KO mice are hyperphagic and
      yet eat more when administered exogenous MCH. Changes in taste preference or
      alcohol metabolism do not appear to be important for the increased alcohol
      drinking in KO mice.

PMID- 17550370
TI  - Component cognitive and motor processes of the digit symbol test: differential
      deficits in alcoholism, HIV infection, and their comorbidity.
AB  - BACKGROUND: Alcoholism (ALC) is highly prevalent in patients with human
      immunodeficiency virus (HIV) infection (HIV), and those with comorbidity
      (ALC+HIV) may suffer compounded deficits in cognitive and motor functions
      affected by both conditions. Given that each disease can adversely affect motor,
      visuospatial, and executive functions, we used an expanded version of the Digit
      Symbol (DS) test to assess the separate and combined effects of ALC and HIV
      infection on these cognitive and motor components. METHODS: Participants were 44
      ALC, 43 HIV, 55 ALC+HIV, and 49 normal controls (NC). We modified DS test
      administration to assess sustained attention (grid completion speed), associative
      learning (number of boxes completed in 15-second epochs), and incidental learning
      (total number-symbol pairs correctly recalled) and also used ancillary tests of
      fine motor, visuospatial, and executive functions to assess their relationship
      with the different components of DS performance. All scores were corrected for
      age and education based on NC performance. RESULTS: Neither single diagnosis
      group-ALC nor HIV-was impaired on DS score or grid completion speed compared with
      the NC group, but the dual-diagnosis ALC+HIV group was impaired. Greater lifetime
      alcohol consumption was associated with longer grid completion time in both ALC
      and ALC+HIV. The HIV group demonstrated associative learning on DS but ALC+HIV
      and ALC did not. All groups performed similarly on incidental learning. Multiple
      regression analyses demonstrated that executive functions, assessed by Color
      Trails 2, predicted traditional DS performance in all groups. Fine Finger
      Movement additionally predicted traditional DS performance and grid completion
      speed in HIV. Visuospatial function, assessed by ability to copy the Rey
      Osterrieth complex figure, did not contribute independently to DS performance in
      either alcohol group. CONCLUSIONS: Alcoholism combined with HIV infection
      resulted in deficits in visuospatial psychomotor function, as assessed by the DS
      test, although deficits were not observed in either disease condition alone.
      Neither alcohol group showed associative learning, and both had compromised
      sustained attention. Combined cognitive and motor adverse effects of alcoholism
      and HIV infection were manifest in psychomotor speed, sustained attention, and
      associative learning of visuospatial material and are testimony to the dangers of
      alcohol abuse even in relatively healthy patients with HIV infection.

PMID- 17550371
TI  - Effect of the adenosine A2a receptor antagonist 3,7-dimethyl-propargylxanthine on
      anxiety-like and depression-like behavior and alcohol consumption in Wistar Rats.
AB  - BACKGROUND: It has been suggested that the reinforcing properties of ethanol are
      in part mediated via an A2 activation of cAMP/PKA signaling in the nucleus
      accumbens, predicting that administration of an A2a antagonist might reduce
      ethanol reward and consumption. We therefore examined the effect of the adenosine
      A2a receptor antagonist 3,7-dimethylpropargylxanthine (DMPX, 3, and 10 mg/kg
      intraperitoneal) on alcohol reinforcement, anxiety-related, depression, and
      rewarding behaviors in nonselected Wistar rats. METHODS: Operant ethanol self
      administration was used for examining alcohol intake, elevated plus-maze and
      Vogel conflict test for anxiety-related behavior, Porsolt swim test for
      depression-like behavior, and conditioned place preference for examination of the
      rewarding properties of the drug. RESULTS: 3,7-Dimethylpropargylxanthine
      decreased lever-pressing for ethanol in a dose-dependent manner. When analyzed as
      percentage of pretreatment baseline, maximum suppression was approximately 60%
      (39+/-7.5 vs 98+/-12%, mean+/-SEM, p=0.017). This effect was behaviorally
      specific, as no effect was found on the water lever. In agreement with previously
      published data, stimulation of locomotion was found (beam-breaks: 3590+/-540 vs
      2475+/-240, 10 mg/kg vs saline, p=0.048). No anxiety-modulating effects were seen
      in either the elevated plus-maze or the Vogel conflict test. 3,7
      Dimethylpropargylxanthine was not found to have intrinsic rewarding properties in
      the conditioned place preference model. CONCLUSIONS: In summary, DMPX produced a
      robust and behaviorally selective reduction of ethanol reinforcement, while
      anxiety-modulating effects were less consistent. These results bring further
      support to a role for adenosine in the regulation of ethanol consumption and
      possibly alcohol addiction/abuse, and the A2a receptor as a potential target for
      the treatment of alcoholism and alcohol abuse.

PMID- 17550372
TI  - Interleukin-13-induced type II polarization of inflammatory macrophages is
      mediated through suppression of nuclear factor-kappaB and preservation of
      IkappaBalpha in a T cell lymphoma.
AB  - Spontaneously arising transplantable T cell lymphoma, designated as Dalton's
      lymphoma (DL), is characterized by a highly invasive and deleterious nature
      almost completely paralysing the host immune system. The level of interleukin
      (IL)-13 is elevated in serum and ascitic fluid of the DL-bearing host. IL-13 is a
      potent immunosuppressive cytokine and is an alternative activator of macrophages
      that suppresses the production of nitric oxide (NO) and expression of inducible
      nitric oxide synthase (iNOS), and proinflammatory cytokines. The expression of
      iNOS and proinflammatory cytokines are dependent largely upon the activation of
      nuclear factor-kappaB (NF-kappaB). Activation of NF-kappaB involves the
      degradation of cytoplasmic inhibitor IkappaBalpha, allowing the nuclear
      translocation of NF-kappaB and thereby transcription of the iNOS gene. Therefore,
      in this study we sought to determine whether the alternative activation or type
      II polarization of macrophages induced by IL-13 is mediated by the suppression of
      NF-kappaB and cytoplasmic preservation of IkappaBalpha. Western blot analysis and
      electrophoretic mobility shift assay (EMSA) indicate that tumour-associated
      macrophages (TAM) or polarized type II macrophages are due to preserved protein
      expression of IkappaBalpha, and therefore suppressed NF-kappaB nuclear
      translocation. These findings suggest that IL-13 may operate through the
      suppression of NF-kappaB activation and preservation of IkappaBalpha.

PMID- 17550373
TI  - CXCL9 and 11 in patients with pulmonary sarcoidosis: a role of alveolar
      macrophages.
AB  - Interferon-inducible protein-10 (IP-10)/CXCL10, which is a ligand for CXC
      chemokine receptor 3 (CXCR3), is known to be involved in the pathogenesis of
      pulmonary sarcoidosis. However, the roles of monokine induced by interferon gamma
      (Mig)/CXCL9 and interferon-inducible T cell alpha chemoattractant (I-TAC)/CXCL11,
      which are also CXCR3 ligands, remain unclear. Mig/CXCL9, IP-10/CXCL10 and I
      TAC/CXCL11 in both bronchoalveolar lavage fluid (BALF) and serum in patients with
      pulmonary sarcoidosis were measured by enzyme-linked immunosorbent assay (ELISA).
      The expression of these chemokines in alveolar macrophages was examined using
      ELISA, quantitative real-time polymerase chain reaction and immunostaining. In
      BALF, Mig/CXCL9 and IP-10/CXCL10 were significantly elevated in stage II
      sarcoidosis as compared with the levels in healthy volunteers. In serum,
      Mig/CXCL9 and I-TAC/CXCL11 were increased in stage II of the disease. The levels
      of all CXCR3 ligands in BALF were correlated with the numbers of both total and
      CD4(+) lymphocytes. Alveolar macrophages were stained positive for all CXCR3
      ligands and produced increased amounts of these chemokines. Positive staining of
      the three chemokines was also observed in the epithelioid and giant cells in the
      sarcoid lungs. These findings suggest that Mig/CXCL9 and I-TAC/CXCL11 as well as
      IP-10/CXCL10 play important roles in the accumulation of Th1 lymphocytes in
      sarcoid lungs.

PMID- 17550374
TI  - Internal prostaglandin synthesis augments osteoprotegerin production in human
      gingival fibroblasts stimulated by lipopolysaccharide.
AB  - Periodontitis is an inflammatory bone disease caused by Gram-negative anaerobic
      bacteria. Osteoclast differentiation is regulated by the balance between receptor
      activator of nuclear factor kappa B ligand (RANKL) and osteoprotegerin (OPG). The
      purpose of this study was to examine the mechanism of OPG production in human
      gingival fibroblasts (HGF) stimulated by lipopolysaccharide (LPS) from
      periodontopathic bacteria. The expressions of Toll-like receptor 2 (TLR-2) and
      TLR-4 in HGF were examined using flow-cytometry. HGF were stimulated with whole
      cell extracts or LPS from Actinobacillus actinomycetemcomitans and Porphyromonas
      gingivalis with or without polymyxin B, a LPS inhibitor. In addition, HGF were
      stimulated with LPS, prostaglandin E(2) (PGE(2)), various agonists of PGE
      receptors (EP1, EP2, EP3 and EP4 agonists) with or without indomethacin (IND), a
      prostaglandin synthesis inhibitor. OPG and PGE(2) production was measured using
      an enzyme-linked immunosorbent assay (ELISA). HGF expressed both TLR-2 and TLR-4.
      Both A. actinomycetemcomitans and P. gingivalis LPS augmented OPG expression in
      HGF. Whole cell extracts from A. actinomycetemcomitans and P. gingivalis
      augmented OPG production by HGF; the augmentation was suppressed by polymyxin B.
      IND suppressed OPG production in LPS-stimulated HGF. PGE(2) stimulated HGF to
      produce OPG. EP1 and EP2 agonists, but not EP3 and EP4 agonists, increased OPG
      production by HGF. These results suggest that LPS-induced OPG production by HGF
      is regulated via EP1 and/or EP2 receptors by endogenously generated PGE(2).

PMID- 17550375
TI  - Microtubules tethered at epithelial cell junctions by dynein facilitate efficient
      junction assembly.
AB  - Efficient remodeling of cell-cell adhesions is critical during development and
      morphogenesis. Junctional components must be specifically and rapidly transported
      to sites of junction assembly. In this study, we show a mechanism by which this
      targeted trafficking may occur. Microtubules target epithelial adherens
      junctions, and the number of microtubules both projecting to and tethered at
      sites of contact is increased during junction assembly, consistent with an
      increased need for new material at the nascent junction. Cytoplasmic dynein is
      localized to sites of cell-cell contact, and microtubules project to dynein
      patches where they become tethered. Microinjection of anti-dynein antibodies
      disrupts the tethering of microtubules, showing that the motor anchors them.
      Furthermore, disruption of dynein inhibits junction formation.
      Immunocytochemistry with antibodies to p120 catenin support the hypothesis that
      tethered microtubules serve as tracks for delivery of new components to forming
      junctions, suggesting a model in which material is targeted for delivery to sites
      of need through microtubules tethered by dynein.

PMID- 17550376
TI  - Latent transforming growth factor binding protein 4 (LTBP-4) is downregulated in
      human mammary adenocarcinomas in vitro and in vivo.
AB  - Transforming growth factor beta (TGF-ss) is able to inhibit proliferation of
      epithelial cells and is involved in the carcinogenesis of human mammary tumours.
      Three latent transforming growth factor-beta binding proteins (LTBP-1, -3 and -4)
      are involved in TGF-beta function. The aim of the study was to analyze the
      expression profiles of TGF-beta 1 and 2 and LTBP-4 in human mammary carcinoma
      cell lines as well as in human mammary tumours. Expression analysis was performed
      at the transcription and protein level under in vivo and in vitro conditions.
      LTBP-4 expression was quantitatively analysed in human carcinomas of the mammary
      gland and in healthy mammary tissues of the same patients. Downregulation of LTBP
      4 in all investigated human mammary tumours compared to normal tissues could be
      demonstrated. Results also revealed that protein levels of TGF-beta 1 are
      downregulated and of TGF-beta 2 are upregulated in human mammary carcinoma cell
      lines compared to primary (normal) human mammary epithelial cells. LTBP-4
      reduction in neoplasms leads to a possible decrease of TGF-beta 1 extracellular
      deposition with reduced TGF-beta 1 bioavailability. TGF-beta 2 was upregulated,
      which indicates a possible compensatory mechanism. This study demonstrated a
      possible functional role of LTBP-4 for TGF-beta bioavailability with respect to
      carcinogenesis of human mammary tumours in vivo and in vitro.

PMID- 17550377
TI  - LAMPs and ABH histo-blood group antigens in granulation tissue.
AB  - Endothelial cells are major participants in angiogenic processes accompanying
      wound repair. The functions of ABH histo-blood group antigens (HBGAs) and
      lysosome-associated membrane proteins LAMP-1 and LAMP-2 in endothelial cells of
      granulation tissue are currently unkown. Here we hypothesize that HBGAs and LAMPs
      enrich the phenotypic characteristics of endothelial cells and might be
      implicated in the plasticity of granulation tissue. Immunohistochemistry revealed
      permanent expression of HBGAs in the cytoplasm of endothelial cells of all
      sprouting capillaries regardless of the organ examined. A modulation in both the
      localization and the intensity of the signal for LAMPs was observed.
      Interestingly, LAMP-1 showed a more intensive staining compared to LAMP-2. LAMP-1
      was found in the cytoplasm, as well as on plasma membranes of endothelial cells.
      We present the first comparative immunohistochemical study of the expression of
      HBGA and LAMPs in endothelial cells of granulation tissue. Novel evidence for
      modulating LAMP reactivity is reported. Our results suggest that both
      glycoconjugates might contribute to the process of neoangiogenesis and tissue
      remodeling in wound healing.

PMID- 17550378
TI  - Standardizing evaluation of sarcoma proliferation- higher Ki-67 expression in the
      tumor periphery than the center.
AB  - Soft tissue sarcomas often present as large and histopathologically heterogenous
      tumors. Proliferation has repeatedly been identified as a prognostic factor and
      immunostaining for Ki-67 represents the most commonly used proliferation marker.
      There is, however, a lack of consensus on how to evaluate Ki-67 staining
      regarding optimal cut-off levels, selection of tumor areas, and the number of
      tumor cells to evaluate. We assessed the impact of targeting peripheral versus
      central tumor areas using tissue microarray-based staining for Ki-67 throughout
      the tumor diameter in 25 leiomyosarcomas. In 18/25 tumors, Ki-67 expression was
      higher in the tumor periphery. If 10% staining tumor nuclei was used as cut-off
      and the maximal Ki-67 staining section in the tumor periphery was considered,
      21/25 tumors would have been classified as highly proliferative compared to 14/25
      if the tumor center had been analyzed. Similar results were obtained also when
      higher cut-off levels were used and if the mean expression rather than the
      maximal expression was considered and the differences were neither caused by
      necrosis nor by hypoxia (assessed as HIF-1alpha expression). Our findings suggest
      that the determination of proliferation in soft tissue sarcomas should be
      standardized for clinical application of Ki-67 as a prognostic marker.

PMID- 17550379
TI  - AMACR is highly expressed in gastric adenomas and intestinal-type carcinomas.
AB  - Alpha-methylacyl-CoA racemase (AMACR) is a novel tumor biomarker expressed in a
      number of neoplasms, including colorectal and prostatic adenocarcinomas. However,
      AMACR expression has not been investigated in preneoplastic and neoplastic
      lesions of the stomach. Using immunohistochemistry we studied the expression of
      AMACR in normal gastric mucosa (n=32), intestinal metaplasia (n=26), adenomas
      (n=29) and adenocarcinomas (n=132) of the stomach from 135 patients. Synchronous
      adenocarcinomas arising in the background of adenomas were observed in 26 cases.
      AMACR immunoreactivity was not observed in all normal gastric mucosa. Tissue from
      intestinal metaplasia, adenomas, and adenocarcinomas was positive in 7.7% (2/26),
      79.3% (23/29), and 62.9% (83/132) of cases, respectively. The difference in AMACR
      expression between adenomas or adenocarcinomas and non-neoplastic mucosa was
      statistically significant (p=0.0001). Moreover, intestinal-type carcinomas showed
      significantly higher expression of AMACR (69.8%) compared to diffuse-type
      carcinomas (47.2%) (p=0.02). Our results indicate that as well as being an
      additional diagnostic tool, altered AMACR expression in gastric adenomas and
      intestinal-type carcinomas suggests that AMACR may be involved early in the
      development of intestinal-type gastric carcinomas.

PMID- 17550380
TI  - Effect of an extract of the mushroom Agaricus blazei Murill on expression of
      adhesion molecules and production of reactive oxygen species in monocytes and
      granulocytes in human whole blood ex vivo.
AB  - We have reported that an extract of the edible officinal mushroom Agaricus blazei
      Murill (AbM) stimulates synthesis of pro-inflammatory cytokines in human
      monocytes and vein endothelial cells in vitro and reduces the extent of lethal
      septicemia in mice with bacterial peritonitis. In the present study on human
      monocytes and granulocytes in whole blood ex vivo, we studied the dynamic changes
      of cell adhesion molecules (CD11b, CD62L) and the production of reactive oxygen
      species (ROS) after stimulation with AbM. The presence of AbM resulted in a
      similarly increased expression of CD11b in monocytes and granulocytes, although
      at a lower AbM concentration in monocytes (0.5%) than in granulocytes (2%).
      Furthermore, there was an AbM-mediated decrease in CD62L expression mirroring the
      effect on CD11b expression regarding magnitude and dose response. The
      intracellular production of ROS increased slightly but significantly in
      granulocytes, but not in monocytes stimulated with AbM. The results suggested
      that the major effect of AbM on monocytes and granulocytes was the upregulation
      of CD11b expression, thereby increasing both the phagocytic potential and the
      ablility to induce diapedesis into inflammatory foci. The rich beta-glucan
      content of AbM could play a crucial role in this immune response.

PMID- 17550381
TI  - Expression of cyclooxygenase-2, c-kit, progesterone and estrogen receptors in
      uterine smooth muscle tumors: differential diagnosis.
AB  - We examined the expression pattern of cyclooxygenase-2 (COX-2) and c-kit in
      uterine smooth muscle neoplasms and tried to determine the role of these markers
      in differential diagnosis. Archival tissue from 64 patients with uterine smooth
      muscle neoplasms (20 leiomyomas (LMs), 22 atypical leiomyomas (ALMs), and 22
      leiomyosarcomas (LMSs)) was immunostained with antibodies against estrogen (ER)
      and progesterone receptors (PR), COX-2 and c-kit. 7 of 20 LM cases and 5 of 22
      ALM cases were immunopositive for COX-2, whereas none of the LMS cases stained
      immunopositive (p< or =0.05). 4 of 20 LM cases and 5 of 22 ALM cases were
      immunopositive for c-kit, whereas 15 of 22 LMS cases showed c-kit
      immunopositivity (p< or =0.05). In conclusion, very few LMs and ALMs show COX-2
      immunopositivity. LMSs usually do not express COX-2. COX-2 expression in smooth
      muscle tumors is not a prominent feature. Therefore, COX-2 inhibitors may not be
      useful in LMS therapy. C-kit was significantly expressed in uterine LMSs.

PMID- 17550382
TI  - Clinical outcome of pertussis in Sweden: association with pulsed-field gel
      electrophoresis profiles and serotype.
AB  - In Sweden, acellular pertussis vaccines were introduced at 3, 5 and 12 months of
      age in 1996, after a 17-year hiatus without pertussis vaccination. An intensified
      surveillance of pertussis was initiated in October 1997, including collection of
      clinical data as well as Bordetella pertussis isolates in culture or PCR
      confirmed cases of pertussis among children born from January 1996 to September
      2004. We analysed the association of pulsed-field gel electrophoresis (PFGE)
      profile and serotype with severity of disease for all children followed during
      the first 7 years of the project. There were in all 927 children for whom both
      clinical information and strain characterisation data were available. 260 of
      these children were hospitalised during the pertussis episode. When duration of
      hospital stay was compared between children with different groups of strains,
      characterised by PFGE profile or serotype, there was a significantly higher
      proportion of children with long duration of hospital stay in the most frequent
      PFGE profile group (BpSR11) compared to the PFGE group of all other profiles
      (p=0.041). There was no statistically significant association between serotype
      and hospitalisation rate or duration of hospital stay, neither was there any
      statistically significant association between serotype or PFGE profile and
      duration of spasmodic cough or presence of complications.

PMID- 17550383
TI  - Low frequency of BK virus in prostatic adenocarcinomas.
AB  - BK virus (BKV) exhibits many oncogenic properties and has been associated with a
      variety of tumors in humans. BKV has not been well studied in the context of
      prostate neoplasia; however, an association of BKV with prostatic adenocarcinoma
      has been suggested based on the detection of viral DNA sequences and expression
      of viral proteins in clinical samples. To further investigate the reported
      association of BKV with prostatic adenocarcinoma and the potential role of the
      virus in prostate tumorigenesis, 30 cases of adenocarcinoma of the prostate were
      analyzed for evidence of BKV infection by in situ hybridization and
      immunohistochemistry. In situ hybridization analysis detected BKV DNA in 2 of 30
      (7%) prostatic adenocarcinomas, with positive signals focally identified in less
      than 1% of the neoplastic cells in both cases. However, none of the tumors
      evaluated demonstrated evidence of BKV large tumor antigen expression by
      immunohistochemistry. Among prostatic adenocarcinomas that showed no evidence of
      BKV infection, BKV DNA was focally observed in the adjacent non-neoplastic
      prostate tissue in four cases by in situ hybridization in the absence of BKV
      large tumor antigen immunoreactivity. The findings of the present study indicate
      rare cases of prostatic adenocarcinoma may be associated with BKV infection.
      However, lack of localization of BKV to a large population of the neoplastic
      cells and absence of BKV large tumor antigen expression suggest that the virus
      does not play a role in the pathogenesis of prostate cancer.

PMID- 17550384
TI  - Somatic mutations of BECN1, an autophagy-related gene, in human cancers.
AB  - Evasion of programmed cell death (PCD) is one of the hallmarks of human cancers.
      It is well known that not only apoptosis, but also autophagy, acts as an action
      mechanism of PCD. BECN1 protein is a key regulator of autophagic PCD. The BECN1
      gene that encodes BECN1 protein acts as a haploinsufficient tumor-suppressor
      gene. However, to date, data on BECN1 mutation in human cancer tissues are
      lacking. To explore the possibility that somatic mutation of the BECN1 gene might
      contribute to the development of human cancers, we analyzed the entire coding
      region and all splice sites of the human BECN1 gene for detection of somatic
      mutations in 180 gastric carcinomas, 94 breast carcinomas, 50 acute leukemias, 50
      colorectal carcinomas, 50 hepatocellular carcinomas, and 124 non-small cell lung
      cancers by single-strand conformation polymorphism (SSCP) and DNA sequencing.
      Overall, we detected 11 somatic mutations of the BECN1 gene, including 3 missense
      mutations (N8K, P350R and R389C) in coding sequences and 8 mutations in introns.
      The mutations were observed in five gastric, three colorectal, one lung and one
      breast carcinoma (s). We expressed the three mutations (N8K, P350R and R389C) in
      HT1080 cells, and found that two (P350R and R389C) of them showed only slightly
      decreased cell death activities compared to the wild-type BECN1. This is the
      first report on BECN1 gene mutations in human cancer tissues, and the data
      suggest that point mutations are a rare event in common human cancers and
      probably do not play a major role in cancer pathogenesis.

PMID- 17550385
TI  - Sequence conservation of subdominant HLA-A2-binding CTL epitopes in HIV-1
      clinical isolates and CD8+ T-lymphocyte cross-recognition may explain the immune
      reaction in infected individuals.
AB  - Cytotoxic T-lymphocytes (CTL) are critical for immune control of infection with
      human immunodeficiency virus type-1 (HIV-1) and searches for relevant CTL
      epitopes for immune therapy are ongoing. Recently, we identified 28 HLA-A2
      binding HIV-1 CTL epitopes (1). In this follow-up study we fully genome sequenced
      HIV-1 from 11 HLA-A2(+) patients to examine the sequence variation of these
      natural epitopes and compared them with the patient's CD8(+) T-cell recall
      response. Often the epitope was conserved but only a few patients showed a CD8(+)
      T-cell recall response. This infrequent targeting may be explained by immune
      subdominance. CD8(+) T-cell recall response to a natural epitope could be
      measured despite sequence differences in the patient's virus. T-cell cross
      reaction between such variants could be demonstrated in HLA-A2 transgenic mice.
      Nine infrequently targeted but conserved or cross-reacting epitopes were
      identified in seven HIV-1 proteins. More immunogenic anchor amino acid optimized
      immunogens were designed that induced T-cell cross-reaction with these natural
      epitopes. It is concluded that most of the new CTL epitopes are conserved but
      subdominant during the infection. It is suggested that T-cell promiscuity may
      explain the observed CD8(+) T-cell reaction to epitope variants and it may be
      possible to use the selected immune optimized epitope peptides for therapeutic
      vaccination.

PMID- 17550386
TI  - Collision of invasive serous adenocarcinoma and mature cystic teratoma in the
      ovary. Letter to the editor.

PMID- 17550387
TI  - Neural tube defects and thymic changes.

PMID- 17550389
TI  - Merkel cell carcinoma metastasizing to the kidney mimicking primary
      neuroendocrine renal cancer.
AB  - A 56-year-old male with a history of cutaneous neuroendocrine (Merkel cell)
      carcinoma presented with a solid mass of the left kidney, measuring 10 cm in
      largest diameter. On histology, the tumour was composed of loosely packed uniform
      cells with round-to-oval nuclei and scant cytoplasm. Immunohistochemically, the
      tumour cells diffusely expressed pancytokeratin and neuroendocrine markers, such
      as chromogranin A, synaptophysin and CD56 (NCAM). Distinct paranuclear dot-like
      expression of cytokeratin 20 showed the lesion to be metastatic Merkel cell
      carcinoma. This is the first reported case of Merkel cell carcinoma metastatic to
      the kidney mimicking primary neuroendocrine renal cancer. We discuss the
      differential diagnosis of the tumour and perform a systematic literature review,
      including potential indications for renal tumour biopsy in patients with a
      history of nonrenal malignancy.

PMID- 17550390
TI  - Extreme neutrophil granulocytosis in a patient with anaplastic large cell
      lymphoma of T-cell lineage.
AB  - We describe a 47-year-old male admitted with fever and extreme neutrophil
      granulocytosis (up to 80 x 10(9)/L). All microbiology tests and test for
      autoimmune disease were negative. CT scan showed pulmonary infiltrates
      bilaterally, mediastinal lymphadenopathy and splenomegaly. Conventional
      pathological examination of bone marrow and lymph node biopsies did not
      demonstrate malignant cells and inflammatory disease was suspected. The patient
      died of multiorgan failure 23 days after admission. Autopsy showed neutrophil
      infiltration of several organs. Immunohistochemistry and cytogenetics postmortem
      led to a diagnosis of anaplastic large cell lymphoma (ALCL) of T-cell lineage.
      Involvement of peripheral blood with leukemoid reaction is a rare manifestation
      of ALCL. This case emphasizes the importance of immunophenotyping in unexplained
      extreme granulocytosis.

PMID- 17550391
TI  - Non-functioning mediastinal parathyroid adenoma with sarcoid-like granulomatous
      lymphadenopathy.
AB  - Non-secretory parathyroid adenomas arising in an ectopic parathyroid gland are
      rare. We report a case of non-functioning anterior mediastinal parathyroid
      adenoma associated with mediastinal lymphadenopathy caused by sarcoid-like
      granulamatous inflammation.

PMID- 17550392
TI  - Carcinosarcoma ex recurrent pleomorphic adenoma of the submandibular gland.
AB  - We report a case of carcinosarcoma ex recurrent pleomorphic adenoma in the
      submandibular region of a 56-year-old Japanese man. He presented with a 2-year
      history of a rapidly growing mass in the submandibular region. He reported
      undergoing excision of a nodule in the same region 10 years earlier. Incisional
      biopsy confirmed the diagnosis of pleomorphic adenoma. The lesion was excised
      surgically. The resected tumor measured 40 x 20 mm and was composed of two large
      nodules and multiple small satellite nodules in the subcutaneous tissue.
      Histopathologically, one large nodule was carcinosarcoma while the other large
      nodules and small satellite nodules were pleomorphic adenoma. The former large
      nodule showed a variegated pattern with carcinomatous components (poorly
      differentiated adenocarcinoma, salivary duct carcinoma, squamous cell carcinoma
      and undifferentiated carcinoma) and sarcomatous components (spindle cell sarcoma,
      chondrosarcoma, liposarcoma and rhabdomyosarcoma). Based on the clinical history
      and histopathology, we consider the lesion to have originated from recurrent
      pleomorphic adenoma.

PMID- 17550406
TI  - Central inhibition of opioid receptor subtypes and its effect on haemorrhagic
      hypotension in conscious sheep.
AB  - AIM: To investigate the contribution of cerebral mu-, kappa- and delta-opioid
      receptors in causing the hypotension, bradycardia and renal hypoperfusion evoked
      by haemorrhage. METHODS: Adult conscious ewes were bled continuously from a
      jugular vein until mean arterial blood pressure (MAP) was reduced to below 50
      mmHg. Starting 30 min before and continuing until 60 min after haemorrhage either
      artificial cerebrospinal fluid (control), d-Phe-Cys-Tyr-d-Trp-Orn-Thr-Pen-Thr
      NH(2) (CTOP micro-receptor antagonist), ICI 174,864 (delta-receptor antagonist)
      or nor-binaltorphimine dihydrochloride (nor-BNI, kappa-receptor antagonist) were
      infused intracerebroventricularly. In a randomized crossover fashion the effect
      of antagonizing one central opioid receptor subtype was compared to control
      experiments in the same animal (n = 6 in all groups). RESULTS: Compared to
      corresponding controls, nor-BNI and ICI 174,864 significantly increased the
      haemorrhage volume needed to reduce MAP to below 50 mmHg (+4.7 mL kg(-1), SD 1.8
      and +3.1 mL kg(-1), SD 3.0 respectively). In the nor-BNI group this was
      accompanied by a significantly augmented tachycardia before MAP fell. Both nor
      BNI and ICI 174,864 also postponed haemorrhagic bradycardia and prolonged
      adequate blood flow to the kidney. The infusions did not affect the circulation
      per se or the recovery after haemorrhage. The micro-opioid receptor blockade had
      no effect on baseline circulation or the response to haemorrhage. CONCLUSION:
      Activation of kappa- and delta-opioid receptors adjacent to the ventricular
      compartment contributes to initiating haemorrhagic hypotension and bradycardia in
      conscious sheep. However, other parts of the brain and different receptors are
      likely to play a role as well.

PMID- 17550408
TI  - Muscle fatigue resistance during stimulated contractions is reduced in young male
      smokers.
AB  - AIM: To determine whether muscle function is compromised in healthy smokers in
      comparison with activity-matched non-smokers. METHODS: Nine male smokers (aged
      22.2 +/- 2.5 years: mean +/- SD) with a smoking history of 2.5 +/- 3.1 pack
      years, and ten male control participants (25.4 +/- 2.9 years) matched for
      physical activity level participated in this study. Knee extensor strength was
      measured using isometric maximal voluntary contractions. Voluntary activation of
      the quadriceps and co-activation of the biceps femoris were determined using
      interpolated twitches and surface electromyography respectively. The frequency
      torque relationship and fatigue resistance were assessed with electrically evoked
      contractions. A fatigue index was determined as the ratio of final torque to
      initial torque during a series of isometric contractions (2 min; 30 Hz; 1 s
      contraction/1 s rest). Quadriceps anatomical cross sectional area was measured
      with MRI at 50% of femur length. RESULTS: Maximal voluntary contraction torque,
      quadriceps anatomical cross sectional area, knee extensor torque/quadriceps cross
      sectional area, activation, co-activation and force-frequency relationship were
      similar, whereas the fatigue index was 17% lower in smokers than non-smokers.
      CONCLUSION: In young men smoking does not significantly affect quadriceps muscle
      mass and contractile properties, but does reduce fatigue resistance of the
      quadriceps muscle, which was not attributable to differences in physical
      activity.

PMID- 17550407
TI  - Distinct labelling of fusion events in rat lactotrophs by FM 1-43 and FM 4-64 is
      associated with conformational differences.
AB  - AIM: Conformational analysis of fluorescent styryl dyes FM 1-43 and FM 4-64 was
      undertaken to clarify if distinct activity-dependent labelling of single
      lactotrophs vesicles and plasma membrane by two dyes is associated with their
      structural differences. METHODS: The activity-dependent labelling of single
      vesicles and plasma membrane by FM 1-43 and FM 4-64 was studied using confocal
      microscopy. The fluorescence intensity of vesicles fused with the plasma
      membrane, and the plasma membrane alone was measured; the ratio of their
      respective peak amplitudes was calculated. The conformational analysis of FM 1-43
      and FM 4-64 was further undertaken by employing the Monte Carlo approach to
      search the conformational space of these molecules. RESULTS: In FM 1-43 staining
      of vesicles and plasma membrane, the ratio of the fluorescence peak amplitudes
      (vesicle vs. plasma membrane) was 2.6 times higher in comparison with FM 4-64
      staining. In FM 4-64 molecule the low-energy conformations are distributed in
      three conformational states (consisting of 3, 4 and 2 conformers respectively) in
      which the proportion of the molecules residing in a given state is 62%, 28% and
      9% respectively. In FM 1-43 the conformation distribution is limited to just one
      conformational state with three approximately equally populated conformers what
      can be explained by greater intrinsic rigidity of the molecule. CONCLUSIONS: The
      observed structural characteristics of FM 1-43 molecules may account for a higher
      increase in quantum yield and/or binding affinity upon incorporation of the dye
      into the vesicle matrix and therefore stronger fluorescence emission in
      comparison with FM 4-64.

PMID- 17550409
TI  - 'Time, gentlemen, please' for watchful waiting in prostate cancer?

PMID- 17550410
TI  - A new transportable shock-wave lithotripsy machine for managing urinary stones: a
      single-centre experience with a dual-focus lithotripter.
AB  - OBJECTIVE: To assess the efficacy and safety of a transportable extracorporeal
      shock wave lithotripsy (ESWL) machine, the Modulith SLX-F2(TM) (Storz Medical
      Italia, Rome, Italy), in the management of solitary urinary calculi. PATIENTS AND
      METHODS: The study included 233 patients (mean age 51 years; 172 male, 61 female)
      with symptomatic solitary renal (group A, 170, mean diameter 15.5 mm) or ureteric
      stones (group B, 63, mean diameter 9.5 mm) treated in a tertiary care
      institution. Exclusion criteria for the analysis were: pelvi-ureteric junction
      obstruction, multiple stones, stone diameter >2 cm, stones in a lower calyx with
      unfavourable anatomy, active infection, or impacted ureteric stones. Selected
      patients had ureteric stenting before treatment, and all patients were treated
      with no anaesthesia. Hospitalization, complications and subsequent auxiliary
      procedures were evaluated. Patients were assessed after a single ESWL session and
      after 3 months by a plain abdominal film and renal ultrasonography. Stone-free
      status was defined as no evidence of calculi, and clinical success as the
      presence of stone fragments of <4 mm. An efficiency quotient (EQ) was calculated
      for the ESWL treatment. Pain was assessed using a visual analogue scale. RESULTS:
      The mean number of shocks used was 3779 and the mean (range) treatment time was
      35 (5-55) min. The overall clinical success rate after one ESWL session was 83.7%
      and 82.5% for renal and ureteric stones, respectively, and the overall 3-month
      stone-free rate was 77% and 74.6%, respectively; the overall EQ was 0.64. When
      risk factors for persistent calculi were analysed simultaneously in a logistic
      regression model, only stones of >1 cm were statistically significant (P < 0.05).
      Most patients reported that pain during ESWL was mild to moderate and easily
      tolerated. Only minor complications occurred, with an overall complication rate
      of 3.8%. CONCLUSIONS: This transportable lithotripter is a safe and effective
      device for managing solitary stones throughout the urinary tract. Its main
      advantage is represented by the dual-focus system. Moreover, it shares with other
      contemporary machines several important features such as outpatient setting, no
      need for anaesthesia, easy patient positioning, and the capability of ancillary
      procedures.

PMID- 17550411
TI  - Angiotensin II plays a role in acute murine experimental autoimmune cystitis.
AB  - OBJECTIVES: To investigate whether angiotensin II (AII) receptor antagonism
      decreases the inflammation and oedema in acute murine experimental autoimmune
      cystitis (EAC), as interstitial cystitis (IC) might have an autoimmune component
      and AII has been implicated in autoimmune-mediated vascular congestion, oedema
      and scarring. MATERIALS AND METHODS: Female Balb/cAN mice were divided into three
      treatment groups (eight in each group) that were autoimmunized with bladder
      homogenate to induce EAC. One group received an AII type 1 receptor (AT(1))
      antagonist, one group an AII type 2 receptor (AT(2)) antagonist, and one group
      remained untreated (EAC). A control and sham-injected group were also included.
      After 10 weeks, bladders were removed, sectioned, and stained with haematoxylin
      and eosin. RESULTS: Grossly, there was no thickening or adhesions in the bladders
      of the control or sham-injected mice. In five of seven surviving EAC bladders,
      there were dense adhesions to surrounding peritoneal structures. There were also
      adhesions and bladder thickening in all of the AT(2) antagonist-treated mice
      (though in a milder form) but in only two of seven surviving AT(1) antagonist
      treated mice. There was no inflammation or oedema in the sham and control groups.
      All the EAC bladders were inflamed, with submucosal oedema and urothelial
      detachment from the lamina propria. In the AT(1) antagonist-treated mice there
      was no inflammation or oedema. By contrast, all AT(2) antagonist-treated mice had
      moderate inflammation and minor detachment of the urothelium from the lamina
      propria. CONCLUSIONS: AT(1) receptor blockade ameliorated the inflammatory
      infiltration, submucosal oedema, and urothelial detachment associated with EAC in
      mice. This was achieved to a lesser extent by AT(2) receptor blockade. If some
      patients with IC have a pathophysiology similar to that of EAC mice, there might
      be potential benefit from AII receptor blockade.

PMID- 17550412
TI  - The future magnitude of urological symptoms in the USA: projections using the
      Boston Area Community Health survey.
AB  - OBJECTIVE: To use the population-based data from the Boston Area Community Health
      (BACH) Survey to estimate the likely magnitude (prevalence) of urological
      symptoms in the USA population in 2025, as health-services researchers use
      projections of the likely magnitude of disease to inform decisions on the future
      allocation of health resources. METHODS: Age and gender-specific prevalence rates
      from BACH were combined with USA population projections to estimate the likely
      magnitude of lower urinary tract symptoms (LUTS) and symptoms suggestive of urine
      leakage, painful bladder syndrome (PBlS) and prostatitis (men only). RESULTS: In
      total and accounting for overlapping symptoms, 52 million adults in the USA will
      have symptoms of LUTS, urine leakage, PBlS or prostatitis in 2025. These
      urological symptoms have a large impact on physical and mental aspects of quality
      of life, that is comparable to other chronic conditions. CONCLUSIONS: The future
      magnitude of symptoms indicative of these four urological conditions might reach
      the current level of cardiovascular disease in the USA, which is considered 'a
      modern epidemic.' Our projections have important implications for medical
      education, training of healthcare providers, health-services research, and policy
      and patient education.

PMID- 17550413
TI  - Mood changes, body mass index and bioavailable testosterone in healthy men:
      results of the Androx Vienna Municipality Study.
AB  - OBJECTIVE: To determine whether sex hormones alone or in combination with body
      mass index (BMI) influence mood in men. SUBJECTS AND METHODS: Blood samples were
      taken from 669 manual workers (aged 43-67 years) to measure sex hormone levels,
      in particular bioavailable testosterone (BAT). At the same time BMI was
      calculated. All participants completed the Beck's Depression Inventory (BDI) for
      the evaluation of depression. Then BMI and BAT were correlated to the BDI scores,
      to determine a possible interaction. RESULTS: There was a quadratic main effect
      for BAT on the BDI scores, i.e. an increased risk of depression with an odds
      ratio of 1.871 (P = 0.029) for hypo- and hypergonadal men. Also, there was an
      interaction between BAT and BMI, which was mainly detected in underweight and
      obese men. This U-shaped effect for underweight and obese men was not detected in
      men with a 'normal' weight, who had a significantly linear decrease in the risk
      of depression by changing from the hypogonadal to the eugonadal subgroup, as well
      as for changing from the eugonadal to the hypergonadal subgroup, with a mean odds
      ratio of 0.513 (P = 0.032). CONCLUSIONS: Depression depends on BAT and BMI; in
      men of normal weight, an increase in BAT reduces the risk of depression, which is
      not the case in underweight and obese men. Consequently eugonadal men with normal
      testosterone levels have the lowest risk of depression.

PMID- 17550414
TI  - Does active surveillance for men with localized prostate cancer carry
      psychological morbidity?
AB  - OBJECTIVES: To investigate, in a cross-sectional study, the prevalence of anxiety
      and depression in patients with localised prostate cancer managed by active
      surveillance, compared with those receiving immediate treatment, as active
      surveillance is a relatively new approach to managing this disease, designed to
      avoid 'unnecessary' treatment, but it is unclear whether the approach contributes
      to psychological distress, given that men are living with untreated cancer.
      PATIENTS AND METHODS: A consecutive series of 764 patients with prostate cancer
      were approached in outpatient clinics. Of these, 329 men with localized disease
      (cT1/2, N0/NX, M0/MX) meeting the study entry criteria, completed the Hospital
      Anxiety and Depression Scale (HADS); 100 were on active surveillance, 81 were
      currently receiving radical treatment (radiotherapy + neoadjuvant hormone
      therapy) and 148 had previously received radical radiotherapy. RESULTS: Overall,
      16% (51/329) of patients met the HADS criteria for anxiety and 6% (20/329) for
      depression. Analyses indicated that higher anxiety scores were significantly
      associated with younger age (P < 0.01) and a longer interval since diagnosis (P <
      0.01), but not with management by active surveillance (P = 0.38). Higher
      depression scores were significantly associated with a longer interval since
      diagnosis (P < 0.05), but not with management by active surveillance (P = 0.83).
      CONCLUSION: Active surveillance for managing localized prostate cancer was not
      associated with greater psychological distress than more immediate treatment for
      prostate cancer.

PMID- 17550415
TI  - Renal injury during shock wave lithotripsy is significantly reduced by slowing
      the rate of shock wave delivery.
AB  - OBJECTIVE: To assess the tissue protection afforded by simply reducing the rate
      of shock wave (SW) delivery, compared with studies in the pig in which SW
      lithotripsy (SWL)-induced vascular damage was significantly reduced by initiating
      treatment using low-amplitude SWs. MATERIALS AND METHODS: Juvenile pigs (6-7
      weeks old) were treated with an unmodified lithotripter (HM3, Dornier Medical
      Systems, Kennesaw, GA) at either 120 or 30 SW/min. Treatment was to one kidney
      per pig, with SWs (2000, 24 kV) directed to a lower-pole calyx. After treatment,
      parenchymal haemorrhage was determined morphometrically and expressed as
      percentage of functional renal volume (%FRV). RESULTS: Kidneys treated at 120
      SW/min had focal to extensive subcapsular haematomas. Parenchymal lesions were
      found only at the lower pole, but included regions within renal papillae and the
      cortex. Occasionally, damage extended across the full thickness of the kidney.
      The lesion in the pigs treated at 120 SW/min occupied a mean (sd) of 4.6 (1.7)
      %FRV. Kidneys of pigs treated at 30 SW/min showed no surface bleeding.
      Parenchymal haemorrhage was limited to papillae within the focal volume, and
      measured 0.08 (0.02) %FRV, a significant (P < 0.005) reduction in injury.
      CONCLUSIONS: Slowing the rate of delivery to 30 SW/min has a dramatic protective
      effect on the integrity of the kidney vasculature. This finding in our
      established pig model suggests a potential strategy to improve the safety of
      lithotripsy. As it was shown that a reduced SW rate also improves the efficiency
      of stone fragmentation, a slow rate appears to be a means to improve both the
      safety and efficacy of SWL.

PMID- 17550416
TI  - Naturally produced crystals obtained from kidney stones are less injurious to
      renal tubular epithelial cells than synthetic crystals.
AB  - OBJECTIVE: To determine the differences in cell responses to synthetic and
      biological crystals of calcium oxalate (CaOx) and brushite MATERIALS AND METHODS:
      Nephrolithiasis depends on crystal retention within the kidneys, often promoted
      by crystal attachment to the injured renal epithelium; studies often use various
      crystals that might be injurious to cells and cause the exposure of crystal
      binding molecules on cell surfaces, thus promoting crystal attachment and
      retention. The synthetic crystals used in these studies might be more injurious
      than the biological crystals naturally produced in the kidneys and that form
      kidney stones. We exposed the renal epithelial cell line NRK 52E in vitro to CaOx
      or brushite crystals at 67 or 133 microg/cm(2) for 3 or 6 h. Synthetic crystals
      were purchased and the biocrystals were obtained by pulverizing CaOx and brushite
      stones. We determined the release of lactate dehydrogenase (LDH), hydrogen
      peroxide (H(2)O(2)) and 8-isoprostane (8-IP), and monocyte chemoattractant
      protein-1 (MCP-1), as markers of injury, oxidative stress and inflammation,
      respectively. Cells were also examined after trypan blue staining to determine
      their membrane integrity. We also examined crystals of CaOx by scanning electron
      microscopy both in the native state as well as after decalcification. RESULTS:
      Exposure to both the synthetic and biological crystals resulted in a significant
      increase in LDH release and trypan blue staining, as a sign of crystal-induced
      injury. There was increased production of H(2)O(2) and 8-IP, suggesting the
      development of oxidative stress. In addition MCP-1 production was also
      significantly increased. However, the synthetic crystals caused significantly
      higher increases in all the indicators than the biological crystals. CONCLUSIONS:
      These results indicate that even though both synthetic and naturally produced
      biocrystals invoke a response from the renal epithelial cells, the latter are
      significantly less injurious and inflammatory. Exposure to low concentrations of
      these crystals alone might not invoke an inflammatory response, cause the
      uncovering of crystal binding molecules on epithelial cell surfaces, and promote
      crystal attachment and retention.

PMID- 17550417
TI  - The prevalence of newly diagnosed hyperlipidaemia in men with erectile
      dysfunction.
AB  - OBJECTIVE: To determine the prevalence of newly diagnosed hypercholesterolaemia
      and hypertriglyceridaemia in patients presenting to an andrology clinic with
      erectile dysfunction (ED), and to assess the relationship between serum lipid
      levels and the severity of ED. PATIENTS AND METHODS: In all, 199 consecutive men
      attending an ED clinic were assessed for risk factors for ED; patients completed
      the International Index of Erectile Function (IIEF)-15 questionnaire and provided
      venous blood samples for assaying fasting total cholesterol and total
      triglyceride levels. The proportion of newly diagnosed hyperlipidaemia in
      patients presenting with ED was calculated and related to patient age, total IIEF
      score and severity of ED. RESULTS: Using a threshold of 5.0 mmol/L, there was
      newly diagnosed hypercholesterolaemia in 40% of the men, while there was
      undiagnosed hypertriglyceridaemia (>2 mmol/L) in 29% of the population. There was
      no clear correlation between patient age and the fasting lipid levels, and no
      association between total IIEF-15 score or severity of ED and serum cholesterol
      and triglyceride levels. CONCLUSION: This study shows the high prevalence of
      undiagnosed hypercholesterolaemia and hypertriglyceridaemia in men presenting
      with ED. The opportunity to screen for and treat these risk factors has long-term
      benefits in preventing cardiovascular disease in this group of patients.

PMID- 17550418
TI  - Oxygen binding and its allosteric control in hemoglobin of the primitive
      branchiopod crustacean Triops cancriformis.
AB  - Branchiopod crustaceans are endowed with extracellular, high-molecular-mass
      hemoglobins (Hbs), the functional and allosteric properties of which have largely
      remained obscure. The Hb of the phylogenetically ancient Triops cancriformis
      (Notostraca) revealed moderate oxygen affinity, cooperativity and pH dependence
      (Bohr effect) coefficients: P(50) = 13.3 mmHg, n(50) = 2.3, and Phi = -0.18, at
      20 degrees C and pH 7.44 in Tris buffer. The in vivo hemolymph pH was 7.52.
      Bivalent cations increased oxygen affinity, Mg(2+) exerting a greater effect than
      Ca(2+). Analysis of cooperative oxygen binding in terms of the nested Monod-Wyman
      Changeux (MWC) model revealed an allosteric unit of four oxygen-binding sites and
      functional coupling of two to three allosteric units. The predicted 2 x 4 and 3 x
      4 nested structures are in accord with stoichiometric models of the quarternary
      structure. The allosteric control mechanism of protons comprises a left shift of
      the upper asymptote of extended Hill plots which is ascribable to the
      displacement of the equilibrium between (at least) two high-affinity (relaxed)
      states, similar to that found in extracellular annelid and pulmonate molluscan
      Hbs. Remarkably, Mg(2+) ions increased oxygen affinity solely by displacing the
      equilibrium between the tense and relaxed conformations towards the relaxed
      states, which accords with the original MWC concept, but appears to be unique
      among Hbs. This effect is distinctly different from those of ionic effectors
      (bivalent cations, protons and organic phosphates) on annelid, pulmonate and
      vertebrate Hbs, which involve changes in the oxygen affinity of the tense and/or
      relaxed conformations.

PMID- 17550419
TI  - The noncatalytic C-terminus of AtPOLK Y-family DNA polymerase affects synthesis
      fidelity, mismatch extension and translesion replication.
AB  - Cell survival depends not only on the ability to repair damaged DNA but also on
      the capability to perform DNA replication on unrepaired or imperfect templates.
      Crucial to this process are specialized DNA polymerases belonging to the Y
      family. These enzymes share a similar catalytic fold in their N-terminal region,
      and most of them have a less-well-conserved C-terminus which is not required for
      catalytic activity. Although this region is essential for appropriate
      localization and recruitment in vivo, its precise role during DNA synthesis
      remains unclear. Here we have compared the catalytic properties of AtPOLK, an
      Arabidopsis orthologue of mammalian pol kappa, and a truncated version lacking
      193 amino acids from its C-terminus. We found that C-terminally truncated AtPOLK
      is a high-efficiency mutant protein, the DNA-binding capacity of which is not
      affected but it has higher catalytic efficiency and fidelity than the full-length
      enzyme. The truncated protein shows increased propensity to extend mispaired
      primer termini through misalignment and enhanced error-free bypass activity on
      DNA templates containing 7,8-dihydro-8-oxoGuanine. These results suggest that, in
      addition to facilitating recruitment to the replication fork, the C-terminus of Y
      family DNA polymerases may also play a role in the kinetic control of their
      enzymatic activity.

PMID- 17550420
TI  - Folate salvage in plants: pterin aldehyde reduction is mediated by multiple non
      specific aldehyde reductases.
AB  - Folates undergo oxidative cleavage in vivo, releasing a pterin aldehyde fragment
      that can be re-used in folate synthesis if the aldehyde group is reduced. High
      levels of NADPH-dependent reductase activity against pterin-6-aldehyde and its
      dihydro form were detected in Arabidopsis, pea and other plants; modeling
      predicted that the activity would maintain in vivo pterin aldehyde pools at
      extremely low levels (<0.2 pmol g(-1) FW). Subcellular fractionation showed that
      the pea leaf activity is mainly cytosolic, and anion exchange chromatography
      revealed multiple isoforms, all of which catalyzed reduction of other aldehydes.
      Arabidopsis seed activity likewise comprised various isoforms. An Arabidopsis
      gene (At1g10310) encoding a pterin aldehyde reductase was identified by searching
      the short-chain dehydrogenase/reductase family for proteins predicted to be NADPH
      linked, and sharing conserved residues with reductases that mediate analogous
      reactions. The recombinant protein behaved as a dimer in size exclusion
      chromatography. In addition to pterin aldehydes, it catalyzed the reduction of
      diverse aromatic and aliphatic aldehydes: Vmax values varied <5-fold, but Km
      values ranged from 3.6 microm to 1.7 mm, those for pterin-6-aldehyde and
      dihydropterin-6-aldehyde being 36 and 56 microm, respectively. Activity with
      dihydropterin-6-aldehyde was unusually high at 0 degrees C. The At1g10310
      transcript was most abundant in seeds, but, as expected for multiple isoforms,
      inactivating the At1g10310 gene caused only a minor change in seed pterin
      aldehyde reductase activity. We conclude that pterin aldehyde salvage in plants
      involves multiple, generalist NADPH-linked reductases, and that the At1g10310
      enzyme is typical of these and hence suitable for use in engineering studies of
      folate turnover.

PMID- 17550421
TI  - Primary prevention of type 1A diabetes: are we there yet?

PMID- 17550423
TI  - Polymorphisms of the TNF-alpha gene and risk of celiac disease in T1DM children.
AB  - BACKGROUND: Type 1 diabetes mellitus (T1DM) and celiac disease (CD) frequently
      occur together. Previous reports suggested that the (-308)A variant of the tumor
      necrosis factor-alpha (TNF-alpha) gene is associated either with T1DM or with CD.
      The aim of our study was to determine whether (-308)A and (-238)A allelic
      variants of the TNF-alpha gene might have any impact on the risk of CD in T1DM
      children. METHODS: Three hundred and one T1DM children were enrolled to the
      study. The presence of CD was screened with IgA endomysial antibodies (EMA) test.
      Jejunal biopsy was performed to confirm CD. TNF-alpha-308 and -238 genetic
      variants were tested using the method of restriction fragment length
      polymorphism. RESULTS: The prevalence of CD in the enrolled diabetic children was
      6.3% (19 out of 301 children). The frequency of the (-308)A TNF-alpha variant was
      similar in the CD and the non-CD groups, exceeding the Hungarian healthy
      reference value. The number of (-238)A allele carriers was higher in the CD
      (4/19) than in the non-CD group (17/277) (p < 0.05). CONCLUSIONS: Our study is
      limited by the small number of CD patients. On the basis of our findings,
      carriers of TNF (-308)A allele do not seem to have an increased risk for CD in
      T1DM. The association between TNF-alpha(-238)A allele carrier state and CD
      requires further investigation.

PMID- 17550422
TI  - Study design of the Trial to Reduce IDDM in the Genetically at Risk (TRIGR).
AB  - The hypothesis for this study is that weaning to an extensively hydrolyzed infant
      formula will decrease the incidence of type 1 diabetes (T1D), as it does in all
      relevant animal models for the disease. This will be tested in children who carry
      risk-associated human leukocyte antigen genotypes and have a first-degree
      relative with T1D. The trial will use a double-blind, prospective, placebo
      controlled intervention protocol, comparing casein hydrolysate with a
      conventional cow's milk (CM)-based formula. A secondary aim is to determine
      relationships between CM antibodies, a measure of CM exposure, and diabetes
      associated autoantibodies. To achieve an 80% power for the detection of a 40%
      intervention-induced difference in the development of autoantibodies and
      subsequent diabetes, the study requires 2032 subjects. A multicenter,
      international, collaborative effort is necessary to achieve recruitment targets.
      A collaborative international study group of 78 clinical centers in 15 countries
      has therefore been assembled for this purpose.

PMID- 17550424
TI  - An 18-yr prospective study of pediatric diabetic ketoacidosis: an approach to
      minimizing the risk of brain herniation during treatment.
AB  - BACKGROUND: During the late 1900s, raised intracranial pressure (ICP) during
      treatment of pediatric diabetic ketoacidosis (DKA) surfaced as the most important
      cause of morbidity and mortality in pediatric DKA. The contribution of fluid and
      electrolyte therapy to neurologic deterioration during treatment remains
      controversial. METHODS: We proposed a physiologic approach to treatment of DKA,
      incorporating the principles of rehydration of hypertonic states. Consecutive
      episodes of pediatric DKA were managed using continuous intravenous insulin, an
      individualized assessment of the degree of dehydration, and rehydration solutions
      of tonicity approximating that of the patient. Gradual replacement of the volume
      of deficit after correction of shock, if present, was planned over 48 h with
      special attention to changes in effective osmolality along with intensive
      cardiorespiratory, neurologic, and biochemical monitoring. Mannitol was given for
      signs or symptoms of raised ICP. RESULTS: Six hundred and thirty-five consecutive
      episodes of pediatric DKA were treated from January 1988 to September 2005. Means
      +/- standard deviation (SD) for initial measured concentrations of total carbon
      dioxide, glucose, and urea nitrogen were 7.8 +/- 3.3 mmol/L, 602 +/- 271 mg/dL
      (33.4 +/- 15 mmol/L), and 21 +/- 1 mg/dL (7.4 +/- 3.6 mmol/L), respectively.
      Pretreatment blood gases were available for 477 episodes. The mean initial
      partial pressures of arterial and venous carbon dioxide +/- SD were 16.8 +/- 7
      mmHg (kP(a)CO(2)= 2.24 +/- 0.93) for n = 308 and 26.6 +/- 7 mmHg (kP(v)CO(2)=
      3.54 +/- 0.93) for n = 169, respectively. Although repair was planned to occur
      over 48 h, the mean time to achieve clinical rehydration and correction of DKA
      was 11.6 +/- 6.2 h. Mannitol was given in 35 (5.5%) episodes. There was no
      neurologic morbidity or mortality. CONCLUSION: Management of pediatric DKA using
      this multifaceted physiologic approach and the principles of rehydration
      described is safe and appears to minimize the risk of brain herniation during
      treatment.

PMID- 17550425
TI  - Hydroxybutyrate near-patient testing to evaluate a new end-point for intravenous
      insulin therapy in the treatment of diabetic ketoacidosis in children.
AB  - BACKGROUND: The aim of this study was to assess the clinical application of a
      near-patient testing (NPT) device for capillary blood hydroxybutyrate (HOB)
      measurement in evaluating a new end-point for intravenous insulin therapy in the
      treatment of diabetic ketoacidosis (DKA) in children. METHODS: Children
      fulfilling the criteria for DKA were treated according to an integrated care
      pathway (ICP) with fluid replacement and insulin infusion. We measured capillary
      HOB hourly by NPT (Abbott Optium meter, analytical range 0-6.0 mmol/L), venous
      blood gases 4 hourly, and venous HOB 4 hourly by laboratory enzymatic method and
      tested all urine passed for ketones. Two possible ICP end-points were compared:
      A, pH > 7.3 followed by two successive NPT HOB measurements <1 mmol/L, and B, pH
      > 7.3 and urine ketone free (our current end-point). RESULTS: In 35 patient
      episodes, the ICP was completed (28 to negative ketonuria) without significant
      variation. Before treatment, median (range) laboratory HOB was 9.5 mmol/L (4.6
      15.70 mmol/L), pH 7.18 (6.98-7.38), and standard bicarbonate 11.5 mmol/L (4.3
      18.6 mmol/L). ICP end-point A was reached after 17 h (4-39 h), whereas end-point
      B was not reached until 28 h (14-64 h) after starting treatment. The median lag
      was 11 h (1-36 h). For 59 paired venous samples (excluding samples with
      laboratory HOB >6 mmol/L), the relation between NPT (y) and laboratory (x) HOB
      was y = 0.92x - 0.05, r(2)= 0.94, mean bias -0.25 mmol/L. CONCLUSIONS: (i) Serial
      measurement of NPT HOB allows evaluation of a new, simple, earlier end-point for
      intravenous insulin therapy. (ii) Agreement between NPT and laboratory HOB was
      clinically acceptable for HOB levels within the meter's analytical range.

PMID- 17550426
TI  - Treatment with insulin glargine reduces asymptomatic hypoglycemia detected by
      continuous subcutaneous glucose monitoring in children and adolescents with type
      1 diabetes.
AB  - OBJECTIVE: Unsatisfactory basal insulin substitution may lead to asymptomatic
      hypoglycemia in children and adolescents with type 1 diabetes (T1D). To
      investigate the effects of multiple daily injections before and after changing to
      insulin glargine (IG), continuous glucose monitoring system (CGMS) data were used
      to analyze glycemic control and hypoglycemic episodes during the two different
      therapy regimens. METHODS: Basal insulin therapy was changed to one daily
      injection of IG in 30 pediatric patients with T1D (14 boys and 16 girls; age 4.5
      18.3 yr, median 14.2 yr; diabetes duration 0.5-15.6 yr, median 4.6 yr) having
      elevated fasting glucose or recurrent hypoglycemia despite treatment with
      multiple injection therapy (basal insulin: two to four injections of neutral
      protamine Hagedorn (NPH) and/or zinc lente insulin). Ambulatory CGMS was applied
      before and 6-8 wk after treatment change. Frequency of hypoglycemic and
      hyperglycemic episodes, glucose area under the curve (AUC), and time below 60
      mg/dL and above 180 mg/dL, respectively, were calculated from CGMS data during
      the day (8:00-22:00 hours) and at night (22:00-8:00 hours). RESULTS: Nocturnal
      hypoglycemia was detected by CGMS in 20 patients before and in 12 patients after
      the change to IG (p = .039), whereas both, the number of nocturnal and diurnal
      hypoglycemic episodes, decreased not significantly from 41 to 36 (p = .758) and
      48 to 28 (p = .055), respectively. AUC and time below 60 mg/dL as well as
      hemoglobin A1c (HbA1c) were not significantly different before and after the
      change to IG. CONCLUSION: Under treatment with IG, asymptomatic hypoglycemia was
      reduced without increase of HbA1c.

PMID- 17550427
TI  - ISPAD Clinical Practice Consensus Guidelines 2006-2007. Microvascular and
      macrovascular complications.

PMID- 17550428
TI  - ISPAD Clinical Practice Consensus Guidelines 2006-2007. Other complications and
      associated conditions.

PMID- 17550429
TI  - Dopamine release is impaired in a mouse model of DYT1 dystonia.
AB  - Early onset torsion dystonia, the most common form of hereditary primary
      dystonia, is caused by a mutation in the TOR1A gene, which codes for the protein
      torsinA. This form of dystonia is referred to as DYT1. We have used a transgenic
      mouse model of DYT1 dystonia [human mutant-type (hMT)1 mice] to examine the
      effect of the mutant human torsinA protein on striatal dopaminergic function.
      Analysis of striatal tissue dopamine (DA) and metabolites using HPLC revealed no
      difference between hMT1 mice and their non-transgenic littermates. Pre-synaptic
      DA transporters were studied using in vitro autoradiography with [(3)H]mazindol,
      a ligand for the membrane DA transporter, and [(3)H]dihydrotetrabenazine, a
      ligand for the vesicular monoamine transporter. No difference in the density of
      striatal DA transporter or vesicular monoamine transporter binding sites was
      observed. Post-synaptic receptors were studied using [(3)H]SCH-23390, a ligand
      for D(1) class receptors, [(3)H]YM-09151-2 and a ligand for D(2) class receptors.
      There were again no differences in the density of striatal binding sites for
      these ligands. Using in vivo microdialysis in awake animals, we studied basal as
      well as amphetamine-stimulated striatal extracellular DA levels. Basal
      extracellular DA levels were similar, but the response to amphetamine was
      markedly attenuated in the hMT1 mice compared with their non-transgenic
      littermates (253 +/- 71% vs. 561 +/- 132%, p < 0.05, two-way anova). These
      observations suggest that the mutation in the torsinA protein responsible for
      DYT1 dystonia may interfere with transport or release of DA, but does not alter
      pre-synaptic transporters or post-synaptic DA receptors. The defect in DA release
      as observed may contribute to the abnormalities in motor learning as previously
      documented in this transgenic mouse model, and may contribute to the clinical
      symptoms of the human disorder.

PMID- 17550430
TI  - Chronic NMDA administration to rats up-regulates frontal cortex cytosolic
      phospholipase A2 and its transcription factor, activator protein-2.
AB  - Excessive N-methyl-D-aspartate (NMDA) signaling is thought to contribute to
      bipolar disorder symptoms. Lithium and carbamazepine, effective against bipolar
      mania, are reported in rats to reduce brain transcription of an arachidonic acid
      selective calcium-dependent cytosolic phospholipase A(2) (cPLA(2)), as well as
      expression of one of its transcription factors, activator protein (AP)-2. In this
      study, we determined if chronic administration of NMDA (25 mg/kg i.p.) to rats
      would increase brain cPLA(2) and AP-2 expression, as these antimanic drugs are
      known to down-regulate excessive NMDA signaling. Administration of a daily
      subconvulsive dose of NMDA to rats for 21 days decreased frontal cortex NMDA
      receptor (NR)-1 and NR-3A subunits and increased cPLA(2) activity,
      phosphorylation, protein, and mRNA levels. The activity and protein levels of
      secretory phospholipase A(2) or calcium-independent phospholipase A(2) were not
      changed significantly. Chronic NMDA also increased the DNA-binding activity of AP
      2 and the protein levels of its alpha and beta subunits. These changes were
      absent following acute (3 h earlier) NMDA administration. The changes, opposite
      to those found following chronic lithium or carbamazepine, are consistent with up
      regulated arachidonic acid release due to excessive NR signaling and may be a
      contributing factor to bipolar mania.

PMID- 17550431
TI  - Antibacterial substances of low molecular weight isolated from the blowfly,
      Lucilia sericata.
AB  - Low molecular weight compounds were isolated by high-performance liquid
      chromatography from the maggot or haemolymph extracts of Lucilia sericata
      (Meigen) (Diptera: Calliphoridae). Using gas chromatography-mass spectrometry
      analysis, three compounds were obtained: p-hydroxybenzoic acid (molecular weight
      138 Da), p-hydroxyphenylacetic acid (molecular weight 152 Da) and octahydro
      dipyrrolo[1,2-a;1',2'-d] pyrazine-5,10-dione (molecular weight 194 Da), also
      known as the cyclic dimer of proline (or proline diketopiperazine or
      cyclo[Pro,Pro]). All three molecules revealed antibacterial activity when tested
      against Micrococcus luteus and/or Pseudomonas aeruginosa, and the effect was even
      more pronounced when these molecules were tested in combination and caused lysis
      of these bacteria.

PMID- 17550432
TI  - Intraspecific variation and population structure of the German cockroach,
      Blattella germanica, revealed with RFLP analysis of the non-transcribed spacer
      region of ribosomal DNA.
AB  - Little information is available on genetic variation within and between
      populations of pest cockroaches. In this study, intraspecific HindIII
      polymorphism was investigated in the German cockroach, Blattella germanica
      (Linnaeus) (Dictyoptera, Blattaria: Blattellidae), using restriction fragment
      length polymorphisms (RFLP) of the non-transcribed spacer (NTS) region of
      ribosomal DNA (rDNA). Individual male insects were collected from infestations at
      three different pig farms. Each population was characterized by HindIII
      restriction fragment frequencies and haplotype (a particular X-chromosome
      pattern) frequencies. The inheritance of the X-chromosome HindIII rDNA patterns
      over 12 generations (3 years) follows Mendelian patterns, and the stability of
      this polymorphic marker indicates infrequent genetic recombination of variable
      sites. Although pairwise genetic distance measures were uncorrelated with
      geographical distance, the pattern of genetic differentiation of the three
      cockroach populations suggests that human-mediated transport of cockroaches is an
      important force in shaping the population genetic structure of cockroach
      infestations, at least at the regional scale of 10-100 km. Sequence variation in
      the ribosomal NTS is a useful marker, and RFLP of rDNA is a simple, robust and
      reproducible technique for differentiating recently diverged cockroach
      populations.

PMID- 17550433
TI  - Tissue and life-stage distribution of a defensin gene in the Lone Star tick,
      Amblyomma americanum.
AB  - The transcript sequence of the Amblyomma americanum Linnaeus (Acari: Ixodidae)
      defensin, termed amercin (amn), was ascertained and a 219-bp amn coding region
      identified. The gene encodes a 72-amino acid prepropeptide with a putative 37
      amino acid mature peptide. This gene shows little similarity to either of the
      defensins from Amblyomma hebraeum Koch, the only other Amblyomma species for
      which a defensin has been described. Sequence comparisons with other tick
      defensins reveal amn to be shorter (6 bp or 2 amino acids) than the Ixodes
      scapularis Linnaeus (Acari: Ixodidae) and Dermacentor variabilis (Say) (Acari:
      Ixodidae) defensin sequences. The amercin prepropeptide has 60.8% and 59.5%
      similarity with the I. scapularis and D. variabilis prepropeptides, respectively,
      whereas the mature amercin peptide has 73.7% and 71.1% similarity with the mature
      peptides of these ticks. Similarity with other tick defensins ranges from 42% to
      71%. In A. americanum, defensin transcript was found in the midgut, fat body and
      salivary gland tissues, as well as in the haemocytes. Defensin transcript was
      also present in early-stage eggs (less than 48 h old), late-stage eggs
      (approximately 2 weeks old), larvae and nymphs of A. americanum and I.
      scapularis, both of which are vector-competent for Borrelia spirochetes.

PMID- 17550434
TI  - Detection of Salmonella sp. in Dermanyssus gallinae using an FTA filter-based
      polymerase chain reaction.
AB  - Salmonella spp. bacteria are responsible for some of the most important zoonoses
      worldwide. Because Dermanyssus gallinae (DeGeer) (Acari: Dermanyssidae) has been
      recently reported to be an experimental vector of Salmonella Enteritidis, it
      would be of benefit to evaluate the presence of this bacterium in mites. A
      molecular detection tool associating a simple filter-based DNA preparation with a
      specific 16S rDNA Salmonella sp. polymerase chain reaction (PCR) amplification
      was described. The limit of detection with this method was 2 x 10(4) bacteria per
      mite. To adapt this technique for large-scale studies, two sizes of mite pools
      were tested and a preliminary investigation was carried out on mites from 16
      currently or previously contaminated farms. Mites sampled from one farm of each
      type were positive for Salmonella, suggesting that Dermanyssus could act as a
      reservoir between flocks. In further investigations, it will be necessary to
      carry out a large-scale study to assess the role of D. gallinae in the
      epidemiology of avian salmonellosis.

PMID- 17550435
TI  - Estimating the incidence of fly myiases in Australian sheep flocks: development
      of a weather-driven regression model.
AB  - The blowfly, Lucilia cuprina Wiedemann (Diptera: Calliphoridae), is the primary
      myiasis (strike) fly of sheep in Australia. Most strike occurs in the anal
      perineum area (crutch), but strike to the neck, shoulders, back and withers
      (body) is also important. Regression analysis was used to determine the extent to
      which the weekly incidence of flystrike can be explained by variations in fly
      abundance and/or recent changes in weather, pasture conditions or flock
      management. Strike and flock management data were collected by questionnaire
      surveys of 30-60 sheep properties in each of three major sheep-producing areas in
      southeastern Australia, namely, Gunning (southern New South Wales), Inverell
      (northern New South Wales) and Flinders Island (Bass Strait). After using
      simulation modelling to remove effects due to shearing, crutching and/or
      insecticide treatment, pasture growth index was found to be the most important
      explanatory variable affecting the incidence of all forms of myiasis. Others were
      average weekly air temperature, the amount and frequency of rainfall, relative
      humidity, dung quality index and a factor denoting seasonal effects. Together,
      these variables accounted for 48.4% of the variation in body strike, 56.8% of
      that in crutch strike and 51.9% of that in other forms of strike. Prediction was
      improved by the inclusion of additional lagged variables describing previous
      strike, fly abundance and fly activity. With these additions, the variation
      explained increased to 60.4% for body strike, 68.0% for crutch strike and 58.3%
      for other strikes.

PMID- 17550436
TI  - Deltamethrin-impregnated bednets reduce human landing rates of sandfly vector
      Lutzomyia longipalpis in Amazon households.
AB  - The entomological efficacy of using 25% deltamethrin EC insecticide-treated
      bednets (ITNs) was evaluated against the sandfly Lutzomyia longipalpis Lutz and
      Neiva (Diptera: Psychodidae), the principal vector of zoonotic visceral
      leishmaniasis (ZVL) in Latin America. A crossover field study in Amazon Brazil
      (Marajo Island, Para State) demonstrated that, compared with untreated nets, the
      insecticide increased the barrier effect of nets by 39% (95% confidence interval
      [CI] 34-44%), reduced human landing rates by 80% (95% CI 62-90%) and increased
      the 24-h mortality rate from 0% to 98% (95% CI 93-99%) inside ITNs. The presence
      of an ITN also reduced the human landing rate on unprotected persons outside the
      net in the same room by 56% (95% CI 52-59%), and increased 24-h mortality to 68%
      (95% CI 62-73%) compared to 0.4% (0.1-2.0%) in untreated houses. The reduction in
      human landing rates in ITN rooms was associated with a doubling in the proportion
      of sandflies alighting on walls compared with that in untreated rooms, which was
      attributed to insecticide-induced excito-repellency. There was no evidence that
      sandflies were diverted onto unprotected hosts. Human landing catches inside
      houses peaked between 19.00 hours and 23.00 hours and declined steadily to zero
      at 02.00 hours and thereafter. House-to-house questionnaires established that
      only 34% of households owned at least one net (median two, range 1-8), only 20%
      of the population slept under a net (33% of 0-5-year-old children), and the
      majority (73%) of the population slept in hammocks. Combined data pertaining to
      sleeping times for children and sandfly activity period indicate that > 50% of
      sandfly bites inside houses, and substantially more outside houses, were taken
      before a third of children were potentially protected by a net. This study
      demonstrates the clear entomological efficacy of ITNs against Lu. longipalpis in
      this endemic region. The effectiveness of ITNs at preventing ZVL infection and
      disease has still to be evaluated.

PMID- 17550437
TI  - Molecular differentiation of three closely related members of the mosquito
      species complex, Anopheles moucheti, by mitochondrial and ribosomal DNA
      polymorphism.
AB  - Distinction between members of the equatorial Africa malaria vector Anopheles
      moucheti (Evans) s.l. (Diptera: Culicidae) has been based mainly on doubtful
      morphological features. To determine the level of genetic differentiation between
      the three morphological forms of this complex, we investigated molecular
      polymorphism in the gene encoding for mitochondrial cytochrome oxidase b (CytB)
      and in the ribosomal internal transcribed spacers (ITS1 and ITS2). The three
      genomic regions revealed sequence differences between the three morphological
      forms similar in degree to the differences shown previously for members of other
      anopheline species groups or complexes (genetic distance d = 0.047-0.05 for CytB,
      0.084-0.166 for ITS1 and 0.03-0.05 for ITS2). Using sequence variation in the
      ITS1 region, we set up a diagnostic polymerase chain reaction (PCR) for rapid and
      reliable identification of each subspecies within the An. moucheti complex.
      Specimens of An. moucheti s.l. collected in Cameroon, the Democratic Republic of
      Congo (DRC), Uganda and Nigeria were successfully identified, demonstrating the
      general applicability of this technique.

PMID- 17550438
TI  - Development of a novel sticky trap for container-breeding mosquitoes and
      evaluation of its sampling properties to monitor urban populations of Aedes
      albopictus.
AB  - Collection methods currently used for large-scale sampling of adult Stegomyia
      mosquitoes (Diptera: Culicidae) present several operational limitations, which
      constitute major drawbacks to the epidemiological surveillance of arboviruses,
      the evaluation of the impact of control strategies, and the surveillance of the
      spreading of allochthonous species into non-endemic regions. Here, we describe a
      new sticky trap designed to capture adult container-breeding mosquitoes and to
      monitor their population dynamics. We tested the sampling properties of the
      sticky trap in Rome, Italy, where Aedes (Stegomyia) albopictus is common. The
      results of our observations, and the comparison between sticky trap catches and
      catches made with the standard oviposition trap, are presented. The sticky trap
      collected significantly larger numbers of Ae. albopictus females than any other
      Culicidae species representing >90% of the total catches. A maximum of 83 An.
      albopictus females was collected in a single week. A high correlation (Pearson
      correlation coefficient r= 0.96) was found between the number of females and the
      number of eggs collected by the traps. The functional relationship between the
      number of eggs and the number of adult females was assessed by major axis
      regression fitted to log(1 +x)-transformed trap counts as y= 0.065 + 1.695x. Trap
      samples significantly departed from a random distribution; Taylor's power law was
      fitted to the trap samples to quantify the degree of aggregation in the catches,
      returning the equations s(2)= 2.401 m(1.325) for the sticky trap and s(2)= 13.068
      m(1.441) for the ovitrap, with s(2) and m denoting the weekly catch variance and
      mean, respectively, indicating that eggs were significantly more aggregated than
      mosquitoes (P < 0.0001). Taylor's power law parameters were used to estimate the
      minimum number of sample units necessary to obtain sample estimates with a fixed
      degree of precision and sensitivity. For the range of densities encountered in
      our study area during the Ae. albopictus breeding season, the sticky trap was
      more precise and sensitive than the ovitrap. At low population densities (c. <
      0.1 mosquito/trap), however, the ovitrap was more sensitive at detecting the
      presence of this species. Overall, our results indicate that our new model of
      sticky trap can be used to sample Ae. albopictus females in urban environments,
      and, possibly, other container-breeding Stegomyia mosquitoes (e.g. Aedes
      aegypti). The technical properties of the new trap are discussed with respect to
      its possible application in monitoring the population dynamics of container
      breeding mosquitoes, in studying their bionomics, and in vector surveillance and,
      possibly, control.

PMID- 17550439
TI  - Rubidium marking of Anopheles mosquitoes detectable by field-capable X-ray
      spectrometry.
AB  - We present a mosquito marking technique suitable for mark-release-recapture that
      can be used with a hand-held, portable X-ray fluorescence (XRF) spectrometer,
      which is practical for field measurements. Third instar Anopheles gambiae Giles
      sensu stricto (Diptera: Culicidae) and Anopheles stephensi Liston larvae were
      cultured to pupation in water containing rubidium (Rb) Cl at concentrations up to
      1000 p.p.m. Rb. Anopheles gambiae larvae survived to adulthood at concentrations
      as high as 1000 p.p.m. Rb but suffered pupal mortality and reduced adult
      longevity at high concentrations. We were able to culture An. stephensi at Rb
      concentrations as high as 300 p.p.m. The presence of Rb in adults was evaluated
      using a portable XRF analyser, and we were able to reliably detect Rb above
      background levels in 10-day-old females and 4-day-old males at concentrations
      causing minimal pupal or adult mortality. We observed that Rb marking was not
      permanent, and the concentration declined significantly as adults aged. The low
      cost of labelling with RbCl and the field portability of the spectrometer provide
      a useful means for labelling mosquitoes via breeding sites or in the laboratory
      for mark-release-recapture experiments.

PMID- 17550440
TI  - Using fluorescently labelled M13-tailed primers to isolate 45 novel
      microsatellite loci from the arboviral vector Culex tarsalis.
AB  - Culex tarsalis Coquillett (Diptera: Culicidae) is a highly efficient arbovirus
      vector. Spatial and temporal heterogeneity have been observed in Cx tarsalis for
      phenotypic traits including autogeny, virus susceptibility and host preference.
      Genetic differences between populations may in part explain these observations.
      Using the M13-tailed primer method, we identified 45 novel polymorphic
      microsatellite markers from microsatellite-enriched Cx tarsalis genomic
      libraries. The M13-tailed primer method was more efficient in identifying useful
      loci than traditional screening by acrylamide gel electrophoresis. These markers
      will be useful for investigating genetic questions in this important vector
      mosquito.

PMID- 17550441
TI  - Soft tissue tumors of the hand. 1. Benign.
AB  - Soft tissue tumors of the hand arise from skin, subcutaneous tissue, tendons,
      nerve, and blood vessels. Many of these lesions occur on other parts of the body;
      however, the hand remains a unique site because these tumors have symptoms,
      appearances, treatments, and prognoses that may be quite different than when on
      other parts of the body. Their characteristics and the severity of symptoms vary
      markedly depending on the exact location, size, and type of tumor-and many of
      these tumors can have multiple forms of presentation. Two articles are intended
      to provide an overview of benign (this article) and malignant tumors (subsequent
      issue) of the hand. The rarer and more deleterious tumors are discussed in detail
      while the common tumors and epidermal lesions with which practitioners are
      familiar are briefly overviewed. At the completion of these review articles,
      participants should be able to identify and diagnose various benign and malignant
      hand tumors as well as understand the accepted current treatment of these
      growths.

PMID- 17550442
TI  - Effect of laser resurfacing on p53 expression in photoaged facial skin.
AB  - BACKGROUND: p53 overexpression has been reported in photoaged skin. Meanwhile,
      p53 gene mutations have been implicated as an important factor in the
      pathogenesis of ultraviolet (UV) light-induced skin cancer. OBJECTIVE: The
      objective was to evaluate the effect of laser resurfacing on the epidermal
      thickness and expression of p53 in photoaged skin. METHODS: Specimens were
      obtained from the facial skin of 10 patients before and after 3 months and 1 year
      of treatment using CO(2) (five cases) and erbium (Er):YAG (five cases) lasers.
      Specimens were also obtained from six age-matched controls. These biopsies were
      used for routine histopathology, histometry, and p53 immunoperoxidase staining.
      RESULTS: Both CO(2) and Er:YAG lasers were found to induce a significant decrease
      in p53 expression in biopsies obtained after 3 months (p=.0004 and .002,
      respectively) followed by gradual increase (p=.01 in both groups). A significant
      increase (p<.01) in epidermal thickness was also observed after 1 year of
      resurfacing. This increase, however, is inversely correlated with the level of
      p53 expression in such patients. CONCLUSION: The decrease in epidermal p53
      expression after CO(2) and Er:YAG lasers may account for some of the benefits of
      resurfacing on the epidermis, as well as prevention of actinic neoplasia by
      adjusting any disturbance in the proliferation/apoptosis balance observed in
      photoaged facial skin.

PMID- 17550443
TI  - Treatment of facial acne papules and pustules in Korean patients using an intense
      pulsed light device equipped with a 530- to 750-nm filter.
AB  - BACKGROUND: A rising number of laser- or light-based therapies are addressing the
      need for effective acne treatments with minimal downtime. OBJECTIVE: The purpose
      of this study is to evaluate an intense pulsed light (IPL) equipped with a 530-
      to 750-nm filter for inflammatory acne treatment. PATIENTS AND METHODS: Thirty
      female patients (mean age, 25.7 years) with mild-to-moderate acne were enrolled.
      While using benzoyl peroxide (BP) gel, one side of the face was treated with the
      PR filter (acne filter) of the IPL. RESULTS: All patients experienced the
      reduction of inflammatory lesion counts in both sides of face. There was no
      significant difference between IPL-treated and untreated sides of the face for
      mean papule plus pustule counts, 3 weeks after three sessions. As to red macules,
      63% were good or excellent on the laser-treated side compared to 33% on the
      untreated side. Improvement of irregular pigmentation and skin tone was detected
      on the laser-treated side than the untreated side. CONCLUSION: This new
      wavelength band of IPL system was safe and effective in improving acne red
      macules, irregular pigmentation, and skin tone but did not affect inflammatory
      acne lesion counts on the skin of Asian persons.

PMID- 17550444
TI  - Comparison of phenol and sodium hydroxide chemical matricectomies for the
      treatment of ingrowing toenails.
AB  - OBJECTIVE: Chemical matricectomy is performed mainly by two agents: phenol and
      sodium hydroxide. Both agents have excellent cure rates, but there are no data
      about the comparison of postoperative healing periods. This study was designed to
      compare the postoperative morbidity rates of sodium hydroxide and phenol
      matricectomies. MATERIALS AND METHODS: Forty-six patients with 154 ingrowing nail
      sides were treated with either sodium hydroxide or phenol matricectomy. In the
      postoperative period, the patients were evaluated for the duration and severity
      of pain, drainage, and peripheral tissue destruction; complete healing periods;
      and overall success rates. RESULTS: The incidence of pain was higher in the
      sodium hydroxide group on the first visit, on the second day, but all patients
      became pain-free after that. The incidence and duration of drainage and
      peripheral tissue destruction was significantly higher in the phenol group. The
      mean period for complete recovery was 10.8 days in the sodium hydroxide group,
      whereas it was 18.02 days in the phenol group. The overall success rates in the
      sodium hydroxide and phenol groups were found to be 95.1 and 95.8%, respectively.
      CONCLUSION: Both sodium hydroxide and phenol are effective agents giving high
      success rates, but sodium hydroxide causes less postoperative morbidity and
      provides faster recovery.

PMID- 17550445
TI  - Feasibility of a two-step teledermatologic approach for the management of
      patients with multiple pigmented skin lesions.
AB  - BACKGROUND: Recent studies demonstrating accuracy of teledermatology and
      teledermoscopy in the evaluation of pigmented skin lesions (PSL) have been
      performed only on PSL previously selected by face-to-face examination.
      OBJECTIVES: The objective was to investigate the feasibility of teledermatology
      for the management of individuals exhibiting multiple PSL with a two-step
      procedure. MATERIALS AND METHODS: In the first step, remote consultants selected
      clinically equivocal lesions evaluating a teletransmitted clinical image of
      patients' backs. In the second step, dermoscopic images of selected lesions were
      evaluated. Management recommendations of both steps were compared with face-to
      face. RESULTS: For a total of 465 PSL in 18 patients, the agreement between the
      face-to-face and the two remote experts resulted moderate (kappa value, 0.530
      0.565) in the first step and substantial (kappa value, 0.681-0.703) in the second
      step. CONCLUSIONS: Although there are limitations of this pilot experience
      (population and technical restrictions), our results provide preliminary evidence
      that a two-step teledermatologic approach may be feasible in managing individuals
      with multiple PSL.

PMID- 17550446
TI  - A pilot feasibility study of a rare skin tumor database.
AB  - BACKGROUND: In the United States melanoma is the only individually reported skin
      cancer. There are no large state or national registries for nonmelanoma skin
      cancer. Nevertheless, rare, that is, nonmelanoma, nonepithelial, tumors can also
      be locally aggressive and metastasize. OBJECTIVES: This study's purpose was to
      demonstrate that Mohs surgeons can share data to create a rare skin tumor
      database. This database may serve as a model for a nationwide database. MATERIALS
      AND METHODS: We retrospectively reviewed the surgery logs of five Mohs surgery
      practices in the Houston, Texas, area for rare-nonmelanoma, nonepithelial-skin
      cancers. A total of 42,279 biopsy-proven cancers of the skin treated with Mohs
      micrographic surgery were reviewed. Tumor data including type, prevalence, year
      of treatment, and the treating Mohs surgeon(s) were compiled and analyzed.
      RESULTS: Forty-three types of rare tumors were identified. A total of 317 rare
      tumors were treated. No practice saw more than 28 rare tumor types. Atypical
      fibroxanthoma was the rare tumor most often treated. CONCLUSIONS: Colleagues can
      cooperate to create a database of rare tumors removed by Mohs micrographic
      surgery. A range of tumors greater than that seen in any single practice is now
      available for study. This should provide the impetus for a nationwide rare skin
      tumor database.

PMID- 17550447
TI  - Abnormal nuclear factor (NF)-kappaB signal pathway and aspirin inhibits tumor
      necrosis factor alpha-induced NF-kappaB activation in keloid fibroblasts.
AB  - BACKGROUND: Keloid is characterized with disproportionate extracellular matrix
      accumulation and fibroblast proliferation. Rel/nuclear factor-kappaB (NF-kappaB)
      signal transduction pathway may play an important role in keloid pathogenesis.
      OBJECTIVE: To examine the effect of aspirin on the tumor necrosis factor (TNF)
      alpha-induced NF-kappaB activation in keloid fibroblasts. METHODS: Primary
      cultured fibroblasts were pretreated with aspirin and then stimulated with TNF
      alpha. Proliferation and apoptosis were measured by MTT reduction and flow
      cytometry. Expression of DNA-binding activity of NF-kappaB p65 and cytoplasmic
      IkappaBalpha/p- IkappaBalpha protein levels were determined by Trans AM NF
      kappaB/p65 kit and Western blot, respectively. Subcellular localization of NF
      kappaB p65 and IkappaBalpha were observed with immunofluorescence assay. RESULTS:
      In this study, we demonstrate that TNF-alpha induced NF-kappaB activation in
      keloid fibroblasts, which show more sensitively than the normal skin fibroblasts.
      Aspirin pretreatment can inhibit TNF-alpha-induced activation of NF-kappaB in a
      dose-dependent manner by preventing the phosphorylation and degradation of
      IkappaBalpha and nuclear translocation of NF-kappaB. Moreover, aspirin may
      inhibit keloid fibroblasts proliferation and sensitize keloid fibroblasts to
      apoptosis. CONCLUSION: These results suggest that aspirin could help in
      developing therapeutic interventions for the treatment of keloid scarring.

PMID- 17550448
TI  - Reconstruction of lower eyelid defects using a cross upper eyelid flap composited
      with ear cartilage.
AB  - BACKGROUND: Basal cell carcinomas (BCC) most frequently involve the lower eyelid
      and are treated with total excision. Various techniques have been proposed for
      reconstruction of the excised eyelid. OBJECTIVE: Because most flaps used in such
      techniques are bulky, thinner, and aesthetically more favorable, flaps have been
      sought recently. METHODS: Defects of the lower lid have been closed with a
      combination of cross-flaps and choncal cartilage prepared from the upper eyelid.
      RESULTS: Eleven lower lids from 10 patients operated for BCC were reconstructed.
      All flaps survived. The duration of follow-up was 10 months, and no complications
      such as relapse, ectropion, or lagophthalmus occurred. CONCLUSIONS: The upper
      eyelid flap was found to be an appropriate cover for both the skin and the
      conjunctiva due to its hairless and smooth structure. The outcome in patients
      followed up for a mean of 10 months was successful, cosmetically and
      functionally.

PMID- 17550449
TI  - A latex finger strip and nylon zip-tie combo as a tunable digital tourniquet.
AB  - BACKGROUND: Surgery on digit and nail requires a clear bloodless field that is
      often achieved by a tourniquet. OBJECTIVE: The objective is to present a simple,
      effective, and safe tourniquet for digital surgery. MATERIALS AND METHODS: A
      latex glove and a nylon zip-tie were used. A long strip is cut from the little
      finger tube of a latex glove. This is used for wrapping around the digit for
      exsanguination. The pressure is then maintained with a household nylon zip-tie.
      The finger strip is then cut to expose the operative field ready for surgery. The
      tourniquet pressure can be adjusted by tightening or loosening of the nylon zip
      tie. RESULTS: Exsanguination and a bloodless field can be effectively achieved.
      The long tail of the nylon zip-tie reminds the operator to remove it at end of
      the surgery. CONCLUSION: A latex strip and nylon zip-tie combo serves as a
      simple, effective, and safe tourniquet for digital surgery.

PMID- 17550450
TI  - A better technique for taking Mohs sections involving cartilage.
AB  - BACKGROUND: When excising Mohs layers involving skin and cartilage in the
      conventional manner, it can be difficult to flatten the entire margin onto a
      single plane because of the inelasticity of the cartilage. This is undesirable,
      because it prevents a complete examination of the surgical margin. OBJECTIVE: We
      describe a modified technique for excising cartilaginous specimens that allows
      the entire margin of the specimen to be more easily flattened onto a single
      plane, so that a complete examination of the surgical margin can be performed.
      METHODS: When taking Mohs layers involving skin and cartilage, we propose
      excising an additional 1 to 2 mm of skin and creating edges with flatter bevels
      of 20 degrees to 30 degrees . RESULTS: The modified technique allows the
      peripheral edge of the skin, the peripheral edge of the cartilage, and the deep
      surface of the cartilage to all be easily flattened onto the same plane, so that
      a complete examination of the margins can take place. CONCLUSION: This technique
      allows a more thorough assessment of the margins of the excision, which will
      result in more successful tumor extirpation. This modified technique may be
      limited on cosmetically sensitive areas because it involves excising slightly
      more tissue than the conventional technique.

PMID- 17550451
TI  - Tragus reconstruction after tumor excision with preauricular folded flap.

PMID- 17550452
TI  - Lateral venous ulceration and incompetence of the small saphenous vein.

PMID- 17550453
TI  - Bilateral seroma after suction-curettage for axillary hyperhidrosis in a
      transaxillary breast-augmented patient.

PMID- 17550454
TI  - Development of extensive flat warts after pulsed dye laser treatment of a port
      wine stain.

PMID- 17550455
TI  - Generalized lichenoid reaction from tattoo.

PMID- 17550456
TI  - Treatment of recurrent dermatofibrosarcoma protuberans with imatinib mesylate,
      followed by Mohs micrographic surgery.

PMID- 17550457
TI  - Carcinoma cuniculatum arising in focal plantar keratoderma.

PMID- 17550458
TI  - Angiosarcoma developing after conservative treatment for breast carcinoma: case
      report with review of the current literature.

PMID- 17550459
TI  - Squamous cell cancer and human papillomavirus infection in oral lichen planus:
      case report and literature review.

PMID- 17550460
TI  - The setting sun sign: visualizing the margins of a basal cell carcinoma on serial
      frozen sections stained with toluidine blue.

PMID- 17550461
TI  - Topical growth factor efficacy.

PMID- 17550462
TI  - Botulinum toxin overrides depression: not surprising, yet sensational.

PMID- 17550463
TI  - A tattoo reaction in a sentinel lymph node from a patient with melanoma.

PMID- 17550464
TI  - Rotation flap for the reconstruction of alar cartilage agenesis.

PMID- 17550466
TI  - Towards a global dengue research agenda.

PMID- 17550467
TI  - Endogenous reactivation and true treatment failure as causes of recurrent
      tuberculosis in a high incidence setting with a low HIV infection.
AB  - OBJECTIVE: To determine the relative frequencies of reinfection vs. reactivation
      or treatment failure in patients from a high tuberculosis incidence setting with
      a low prevalence of HIV infection. METHOD: We performed DNA fingerprinting on
      serial isolates from one and multiple TB episodes from 97 retreatment patients;
      35 patients had been previously cured, whereas 62 had not. RESULTS: DNA
      fingerprinting patterns of recurrence Mycobacterium tuberculosis isolates of 5 of
      the 35 previously cured patients did not match with those of the corresponding
      initial isolates, indicating reinfection. We did not document reinfection during
      treatment. Isolates from each of the remaining 30 previously cured patients had
      identical DNA fingerprinting results, indicating reactivation. DNA fingerprinting
      patterns of isolates from the 62 patients with persistently positive sputum
      smears were identical, suggesting treatment failure. CONCLUSION: These findings
      suggest that reinfection is not a common cause of relapse and treatment failure
      in this rural predominantly HIV-free population despite the high incidence of TB.

PMID- 17550468
TI  - Risk factors for Schistosoma mansoni and hookworm in urban farming communities in
      western Cote d'Ivoire.
AB  - OBJECTIVES: To identify risk factors for Schistosoma mansoni and hookworm
      infections in urban farming communities, and to investigate small-scale spatial
      patterns of infection prevalence. METHODS: A cross-sectional survey was carried
      out in 113 farming households (586 individuals) and 21 non-farming households
      (130 individuals) from six agricultural zones in the town of Man, western Cote
      d'Ivoire. Heads of households were interviewed on common agricultural activities,
      land and water use, education attainment, socioeconomic status and sanitation
      facilities. Household members provided stool specimens that were processed by the
      Kato-Katz technique and a formol-ether concentration method and diagnosed for S.
      mansoni, hookworms and other soil-transmitted helminths and intestinal protozoa.
      Bayesian statistics were employed for spatial analyses. RESULTS: The prevalences
      of S. mansoni and hookworm in farming households were 51.4% and 24.7%,
      respectively. Risk factors for a S. mansoni infection comprised living in close
      proximity to the Ko River, water contact with irrigation wells and ponds and low
      education attainment. Living in zones of smallholder irrigated rice plots or
      large rice perimeters, using water from domestic wells, and low socioeconomic
      status were risk factors for a hookworm infection. We found significant spatial
      heterogeneity between agricultural zones, with the highest infection prevalences
      of S. mansoni and hookworm in the zone where there was a large rice perimeter.
      CONCLUSIONS: In this urban setting, both S. mansoni and hookworm infections were
      related to specific agricultural activities. Health education and active
      participation of urban farmers for the control of schistosomiasis and soil
      transmitted helminthiasis is recommended.

PMID- 17550469
TI  - Microgeographical and tribal variations in water contact and Schistosoma mansoni
      exposure within a Ugandan fishing community.
AB  - OBJECTIVE: To explore patterns of water contact and Schistosoma mansoni exposure
      by age, sex, tribe and space within a single village. METHODS: For 10 months, we
      systematically observed water contacts made by the 800 inhabitants of a small
      Ugandan fishing village. In order to estimate cercarial exposure, times spent in
      water were weighted by snail infection levels, time of day and degree of
      immersion. RESULTS: There were marked differences in water contact patterns
      between the two main tribes, which inhabited geographically distinct ends of the
      village resulting in geographically distinct spatial patterns of water contact.
      The distributions of the intermediate hosts, Biomphalaria sudanica and
      Biomphalaria stanleyi, also appeared to differ over small distances. This led to
      quite different exposure patterns between the two tribes, particularly amongst
      females. CONCLUSIONS: Schistosoma mansoni exposure can vary markedly within a
      single village. Such non-homogenous patterns of exposure are likely to have wider
      implications for schistosomiasis control programmes and research studies.

PMID- 17550470
TI  - The role of pfmdr1 in Plasmodium falciparum tolerance to artemether-lumefantrine
      in Africa.
AB  - OBJECTIVE: Artemether-lumefantrine (AL), presently the most favoured combination
      therapy against uncomplicated Plasmodium falciparum malaria in Africa, has
      recently shown to select for the pfmdr1 86N allele. The objective of this study
      was to search for the selection of other mutations potentially involved in
      artemether-lumefantrine tolerance and/or resistance, i.e. pfmdr1 gene
      amplification, pfmdr1 Y184F, S1034C, N1042D, D1246Y, pfcrt S163R and PfATP6
      S769N. METHODS: The above mentioned SNPs were analysed by PCR-restriction
      fragment length polymorphism and pfmdr1 gene amplification by real-time PCR based
      protocols in parasites from 200 children treated with AL for uncomplicated P.
      falciparum malaria in Zanzibar. RESULTS: A statistically significant selection of
      pfmdr1 184F mostly in combination with 86N was seen in reinfections after
      treatment. No pfmdr1 gene amplification was found. CONCLUSION: The results
      suggest that different pfmdr1 alleles are involved in the development of
      tolerance/resistance to lumefantrine.

PMID- 17550471
TI  - Is the Expanded Programme on Immunisation the most appropriate delivery system
      for intermittent preventive treatment of malaria in West Africa?
AB  - OBJECTIVE: To investigate the coverage and equity of the Expanded Programme on
      Immunisation (EPI) and its effect on age schedule, seasonality of malaria risk,
      and linked intermittent preventive treatment (IPT) in West Africa. METHOD:
      Secondary analyses of data from a trial of IPT in Ghana. The potential
      effectiveness and impact of EPI-linked IPT in West Africa was calculated using
      the coverage of Diptheria Pertussis Tetanus vaccination obtained from national
      surveys and the reported protective efficacies of IPT. RESULTS: In West Africa,
      where the transmission of malaria is highly seasonal, only 10% of malaria
      episodes in infants would be averted with the current coverage of EPI.
      CONCLUSION: In this setting, the EPI-linked IPT is not necessarily the most
      appropriate approach and alternative IPT schedules and delivery systems are
      needed.

PMID- 17550472
TI  - A multiplex PCR assay that separates Rhodnius prolixus from members of the
      Rhodnius robustus cryptic species complex (Hemiptera: Reduviidae).
AB  - Rhodnius prolixus is one of the most important primary vectors of human Chagas
      disease in Latin America. Its morphology is, however, identical to that of the
      members of the Rhodnius robustus cryptic species complex, which includes
      secondary vectors. The correct identification of these taxa with differential
      vector competence is, therefore, of great epidemiological relevance. We used the
      alignment of 26 mitochondrial cytochrome b haplotypes (663 bp) to select for PCR
      amplifiable species-specific regions. We designed one forward primer on a region
      conserved across all haplotypes, and three reverse primers that anneal to species
      specific regions and amplify fragments of different lengths for R. prolixus (285
      bp) and for members of the two major R. robustus lineages: group I (349 bp) and
      groups II-IV (239 bp). These fragments were easily identifiable on regular 1.5%
      agarose gels. This multiplex PCR assay was successfully tested on 81 specimens
      from six Latin American countries, and used to determine the phylogeographic
      boundaries for each species. It is a simple, objective, and cost-effective assay.
      Its PCR-based nature makes it applicable to any insect developmental stage, as
      well as to dried specimens, and insect remains. It should be particularly useful
      in areas where representatives of these Rhodnius species occur in sympatry.

PMID- 17550473
TI  - Active dispersal by wild Triatoma infestans in the Bolivian Andes.
AB  - Triatoma infestans is the main vector of Chagas disease and target of control
      programmes in the Southern Cone countries. So far Bolivia is the only country
      where true T. infestans wild foci are documented. The dispersal ability for wild
      T. infestans was studied at microgeographical scale in Bolivian Andes, to assess
      the possibility for wild populations to actively recolonize insecticide-treated
      villages. Nine microsatellite loci were used to detect the extent of gene flow
      between neighbouring collecting sites. The detection of restricted gene flow
      between close but distinct sylvatic sites supports the hypothesis that wild T.
      infestans does not disperse by flying at high altitude (2,750 m asl). It
      gradually disperses over small distances by walking within a 'patch' of
      continuous land cover. The genetic differentiation detected between sylvatic and
      domestic populations suggests a limited short-term role of wild insects in the
      process of recolonization of insecticide-treated houses in the Andes.

PMID- 17550474
TI  - Field trial of a low cost method to evaluate hand cleanliness.
AB  - OBJECTIVE: To evaluate a simple low cost method for measuring hand contamination
      as an objective assessment of handwashing practices. METHOD: As part of a larger
      randomized controlled trial of handwashing promotion with soap conducted in
      squatter settlements of Karachi, Pakistan, a randomly selected subset of 52
      mothers in households receiving soap and handwashing promotion and 28 mothers in
      control households directly pressed three fingers of their right hand onto
      MacConkey agar plates on weekly unannounced visits from April to September 2002,
      and monthly from October 2002 to March 2003. The MacConkey plates were incubated
      at 44 degrees C for 24 h, and evaluated for growth of thermotolerant coliform
      bacteria. RESULTS: The proportion of samples that had detectable thermotolerant
      coliforms (50%) was similar in households that received soap and control
      households (52%, P = 0.40). In the week after evaluation of the mothers' hands,
      the proportion of households that reported diarrhoea was similar regardless of
      whether or not the mother had thermotolerant coliforms detected by direct finger
      imprint (18.6%vs. 19.1%, Relative Risk 0.99, 95% CI 0.96, 1.03). CONCLUSIONS: A
      three finger direct imprint test using MacConkey agar for thermotolerant
      coliforms was not a useful method to assess regular handwashing practices with
      soap in Karachi. Developing better measures of handwashing behaviour remains an
      important research priority.

PMID- 17550475
TI  - Characteristics of latrine promotion participants and non-participants;
      inspection of latrines; and perceptions of household latrines in Northern Ghana.
AB  - OBJECTIVES: To examine characteristics of household heads in two districts of
      Northern Ghana who had or had not participated in latrine promotion programmes;
      to inspect latrines; and to explore perceptions of latrine ownership. METHODS:
      One hundred and twenty latrine owners and 120 non-owners were randomly selected
      from all trachoma-endemic villages and interviewed. Structured questionnaires
      assessed demographics, household data, wealth indicators, and perceptions of
      latrine ownership. Latrines were inspected. RESULTS: Latrine owners and non
      owners were similar demographically, but owners were more likely to report any
      education or wealth indicators: any education OR = 2.0, (95% CI 1.2-3.4); large
      family size OR = 4.6 (2.6-8.2); children in school OR = 3.8 (1.3-10.5); and metal
      roof OR = 9.1 (2.0-40.0). All 120 latrine owners were participating in promotion
      programmes; no latrines had been self-built without programme support. Inspection
      showed 73/120 (60.1%) latrines were completed and used. Of the uncompleted
      latrines 41/47 (87.2%) were more than a year old. Programme participants
      (regardless of whether they had a completed latrine) had contributed cash (mean
      16.74 dollars S.D.18.09) and 117/120 had provided labour and/or construction
      materials. The most frequently reported advantages of latrine ownership were
      convenience, cleanliness and health benefits; reported disadvantages were the
      need for maintenance and cleaning and bad odour. CONCLUSIONS: Current latrine
      promotion programmes do not reach all households equally. Joining a latrine
      programme was expensive and did not guarantee latrine ownership; this may cause
      people to lose trust in such programmes. Latrines were perceived to be useful,
      suggesting unmet demand. Reliable and inclusive programmes that provide low cost
      latrines may receive community support.

PMID- 17550476
TI  - Neonatal home care practices in rural Egypt during the first week of life.
AB  - OBJECTIVE: To provide information about home care practices for newborns in rural
      Egypt, in order to improve neonatal home care through preventive measures and
      prompt recognition of danger signs. METHOD: Survey of newborn home care practices
      during the first week of life in 217 households in three rural Egyptian
      Governorates. RESULTS: Many practices met common neonatal care standards,
      particularly prompt initial breastfeeding, feeding of colostrum and continued
      breastfeeding, and most bathing practices. However, several practices could be
      modified to improve neonatal care and survival. Supplemental substances were
      given to 44% of newborns as pre-lacteal feeds, and to more than half during the
      first week. Nearly half (43%) of mothers reported that they did not wash their
      hands before neonatal care, and only 7% washed hands after diaper changes.
      Thermal control was not practiced, although mothers perceived 22% of newborns to
      be hypothermic. CONCLUSIONS: The practices we observed, which are critical for
      newborn survival, could be improved with minor modifications. We provide a
      framework for communicating behaviour change and setting research priorities for
      improving neonatal health.

PMID- 17550477
TI  - Letter to the editors. Secondary or reinfection cutaneous tuberculosis.

PMID- 17550479
TI  - Should fetal therapy be a national priority?

PMID- 17550480
TI  - Twin-to-twin transfusion syndrome: is the future getting brighter?
AB  - The twin-to-twin transfusion syndrome (TTTS) continues to pose a major challenge
      in the area of fetal therapy. Untreated, the mortality and morbidity are
      extremely high, and the fact that there are two structurally normal fetuses at
      risk makes the case for effective in utero therapy even more compelling. Advances
      in therapeutic procedures, in particular the development of selective laser
      photocoagulation of intertwin vascular anastomoses, have improved outcomes, both
      in terms of survival and survival free of disability. This review examines the
      pathophysiology, diagnosis, surveillance, contemporary therapies, expected
      outcomes and ongoing challenges in TTTS.

PMID- 17550481
TI  - Getting an evidence-based post-partum haemorrhage policy into practice.
AB  - BACKGROUND: Post-partum haemorrhage (PPH) is a potentially life-threatening
      complication of childbirth occurring in up to 10% of births. The NSW Department
      of Health (DoH) issued a new evidence-based policy (Framework for Prevention,
      Early Recognition and Management of Post-partum Haemorrhage) in November 2002.
      Feedback from maternity units indicated that there were deficiencies in the
      skills and experience is needed to develop the written protocols and local plans
      of action required by the Framework. METHODS: All 96 hospitals in NSW that
      provide care for childbirth were surveyed. A senior midwife completed a
      semistructured telephone interview. RESULTS: Ninety four per cent of hospitals
      had PPH policies. Among hospitals that provided a copy of their policy, 83% were
      dated after the release of the DoH's Framework, but 22% contained an incorrect
      definition of PPH. Only 71% of respondents in small rural and urban district
      hospitals recalled receiving a copy of the Framework. There was considerable
      variation in the frequency of postnatal observations. Key factors that impede
      local policy development were resources, entrenched practices and centralised
      policy development. Enabling factors were effective relationships, the DoH policy
      directive (Framework), education and organisational issues/time. CONCLUSIONS:
      Greater assistance is needed to ensure that hospitals have the capacity to
      develop a policy applicable to local needs. Maternity hospitals throughout the
      state provide different levels of care and NSW DoH policy directives should not
      be 'one size fits all' documents. Earlier recognition of PPH may be facilitated
      by routine post-partum monitoring of all women and should be consistent
      throughout the state, regardless of hospital level.

PMID- 17550482
TI  - Three-dimensional ultrasound imaging of the levator hiatus in late pregnancy and
      associations with delivery outcomes.
AB  - OBJECTIVE: To determine the correlations between dimensions of the levator hiatus
      in late pregnant nulliparous women, mode of delivery and length of second stage.
      METHODS: This was a prospective observational pilot study of 61 nulliparous women
      seen and examined between 36 and 40 weeks of pregnancy. A translabial ultrasound
      examination was undertaken, and three-dimensional volumes comprising the levator
      hiatus were recorded at rest, during a pelvic floor muscle contraction and on
      Valsalva. The volumes were analysed in a blinded fashion using proprietary
      software to determine linear dimensions and hiatal area. Information regarding
      delivery outcomes and course of labour was obtained from the obstetric database.
      Statistical analysis was undertaken for correlations between hiatal dimensions
      and labour outcomes. RESULTS: No consistent correlations were found between
      levator dimensions and delivery mode. However, an inverse correlation was
      demonstrated between the area of the hiatus, particularly on pelvic floor
      contraction, and length of total second stage. CONCLUSIONS: Levator hiatal
      dimensions are associated with the length of the second stage of labour. Although
      the numbers were small, our findings suggest that the effect of pelvic floor
      structures on progress in labour is worth further study.

PMID- 17550483
TI  - Oxycodone as a component of multimodal analgesia for lactating mothers after
      Caesarean section: relationships between maternal plasma, breast milk and
      neonatal plasma levels.
AB  - BACKGROUND: Oxycodone has become popular for post-Caesarean section (CS)
      analgesia yet it is not currently recommended for use in breast-feeding mothers
      because of limited information on its excretion into breast milk. AIM: To
      investigate the relationship between maternal ingestion of oxycodone after CS and
      the resultant maternal plasma, breast milk and neonatal plasma drug levels up to
      72-h post-partum. METHODS: Fifty breast-feeding mothers taking oxycodone had
      blood and breast milk samples analysed for oxycodone levels at 24 h intervals
      after CS. Forty-one neonates had blood samples taken at 48 h. RESULTS: Oxycodone
      was detected in the milk of mothers who had taken any dose in a 24-h period, with
      significant correlation between maternal plasma and milk levels (R(2) = 0.81).
      The median milk:plasma (M:P) ratio for the same period was 3.2:1. Over the
      subsequent 48 h, the relationship between plasma and milk levels was less strong
      (R(2) = 0.59) and there was a larger range of M:P levels with evidence of
      persistence of oxycodone in the breast milk of some mothers. Oxycodone levels up
      to 168 ng/mL were detected in breast milk (20% > 100 ng/mL). Oxycodone was
      detected in the plasma of one infant. CONCLUSIONS: Oxycodone is concentrated in
      human breast milk up to 72-h post-partum. Breastfed infants may receive > 10% of
      a therapeutic infant dose. However, maternal oxycodone intake up to 72-h post-CS
      poses only minimal risk to the breast-feeding infant as low volumes of breast
      milk are ingested during this period.

PMID- 17550484
TI  - The role of continuous glucose monitoring in clinical decision-making in diabetes
      in pregnancy.
AB  - BACKGROUND: The continuous glucose monitoring system (CGMS) is a novel tool to
      assess 24-h glucose fluctuations. In pregnancies complicated by diabetes, where
      excellent glucose control is desired to improve maternal and fetal outcomes, CGMS
      may have a role in fine-tuning management. AIMS: To assess the usefulness of CGMS
      in pregnant women with diabetes for medical decision-making and to evaluate
      patient tolerability and perception of usefulness. METHODS: Pregnant women with
      diabetes at the Werribee Mercy Hospital were offered CGMS in the setting of their
      standard diabetes care. Treating clinicians were asked if the CGMS altered
      management decisions from those based on conventional glucose monitoring. The
      accuracy of the CGMS was assessed by comparison with the patients' finger-prick
      glucose readings. Patients completed a feedback questionnaire after having the
      CGMS and viewing their results. RESULTS: CGMS traces (n = 68) were obtained in 55
      pregnant women - 37 with gestational diabetes, ten with type 2 and eight with
      type 1 diabetes. Forty-two of 68 (62%) traces were assessed as providing
      additional information which altered clinical management decisions. This included
      showing undetected postprandial hyperglycaemia and overnight hypoglycaemia.
      Subject feedback was generally positive, with 37 of 48 (77%) respondents
      reporting that the benefits of the CGMS outweighed the inconvenience. CONCLUSION:
      CGMS is a well-tolerated clinically useful tool in the management of gestational
      diabetes and pre-existing diabetes in pregnancy.

PMID- 17550485
TI  - Screening for gestational diabetes at antenatal booking in a Malaysian university
      hospital: the role of risk factors and threshold value for the 50-g glucose
      challenge test.
AB  - BACKGROUND: The best method of screening for gestational diabetes (GDM) remains
      unsettled. The 50-g glucose challenge test (GCT) is used in a two-stage screening
      process but its best threshold value can vary according to population. AIMS: To
      evaluate the role of risk factors in conjunction with GCT and to determine an
      appropriate threshold for the one-hour venous plasma glucose with the GCT.
      METHOD: In a prospective study, 1600 women at antenatal booking without a history
      of diabetes mellitus or GDM filled a form on risk factors before GCT. Women who
      had GCT >or= 7.2 mmol/L underwent the 75-g oral glucose tolerance test (OGTT).
      GDM was diagnosed according to WHO (1999) criteria. RESULT: Thirty-five per cent
      had GCT >or= 7.2 mmol/L, 32.6% underwent OGTT and 34.5% of OGTT confirmed GDM.
      The GDM rate in our population was at least 11.4%. Examination of the receiver
      operator characteristic curve suggested that the best threshold value for the GCT
      in our population was >or= 7.6 mmol/L. Multivariable logistic regression
      demonstrated that only GCT >or= 7.6 mmol/L was an independent predictor for GDM
      (adjusted odds ratio 3.7: P < 0.001). After GCT, maternal age and anthropometry,
      OGTT during the third trimester, family history, obstetric history and glycosuria
      were not independent predictors of GDM. CONCLUSIONS: Risk factors were not
      independent predictors of GDM in women with GCT >or= 7.2 mmol/L. GCT threshold
      value >or= 7.6 mmol is appropriate for the Malaysian population at high risk of
      GDM.

PMID- 17550486
TI  - The ADIPS pilot National Diabetes in Pregnancy Audit Project.
AB  - BACKGROUND: Limited resources are available to compare outcomes of pregnancies
      complicated by diabetes across different centres. AIMS: To compare the use of
      paper, stand alone and networked electronic processes for a sustainable,
      systematic international audit of diabetes in pregnancy care. METHODS:
      Development of diabetes in pregnancy minimum dataset using nominal group
      technique, email user survey of difficulties with audit tools and collation of
      audit data from nine pilot sites across Australia and New Zealand. RESULTS:
      Seventy-nine defined data items were collected: 33 were for all women, nine for
      those with gestational diabetes (GDM) and 37 for women with pregestational
      diabetes. After the pilot, four new fields were requested and 18 fields had
      queries regarding utility or definition. A range of obstacles hampered the
      implementation of the audit including Medical Records Committee processes, other
      medical/non-medical staff not initially involved, temporary staff, multiple
      clinical records used by different parts of the health service, difficulty
      obtaining the postnatal test results and time constraints. Implementation of
      electronic audits in both the networked and the stand-alone settings had
      additional problems relating to the need to nest within pre-existing systems.
      Among the 496 women (45 type 1; 43 type 2; 399 GDM) across the nine centres,
      there were substantial differences in key quality and outcome indicators between
      sites. CONCLUSIONS: We conclude that an international, multicentre audit and
      benchmarking program is feasible and sustainable, but can be hampered by pre
      existing processes, particularly in the initial introduction of electronic
      methods.

PMID- 17550487
TI  - Social influences for smoking in pregnancy in south western Sydney antenatal
      clinic attendees.
AB  - This study examined the needs of and barriers to smoking cessation of 677 women
      who attended antenatal clinics in south-west Sydney. More than a quarter (26.3%)
      of the mothers reported smoking at their first antenatal visit. Smokers were more
      likely to be teenagers, single mothers and less likely to have formal education
      or employment. They were less aware of the potential health risks of smoking in
      pregnancy (SIP). High levels of SIP remain a public health problem, and effective
      interventions are needed.

PMID- 17550488
TI  - Reduction in protein S activity during normal pregnancy.
AB  - We investigated the serial changes in blood protein S (PS) and related proteins
      in 11 normal pregnant women. The PS activity decreased significantly in the third
      trimester and reached minimum levels (23.3%) one hour after delivery. Although
      the PS activity was reduced markedly below the normal limits, all the women
      delivered safely. The mechanisms that cause the reduction in PS activity and the
      clinically dangerous conditions involving PS activity during pregnancy warrant
      further investigation.

PMID- 17550489
TI  - A randomised control trial examining the effect of an antioxidant (Menevit) on
      pregnancy outcome during IVF-ICSI treatment.
AB  - BACKGROUND: Evidence has accumulated supporting the role of reactive oxygen
      species (ROS) in the pathogenesis of sperm dysfunction among men with
      infertility. Damage to sperm DNA by ROS can lead to failure of conception,
      miscarriage or potentially even childhood cancer. The objective of this study was
      to examine the effect of male antioxidant treatment on embryo quality and
      pregnancy outcome during in vitro fertilisation-intracytoplasmic sperm injection
      (IVF-ICSI) treatment. METHODS: Sixty couples with severe male factor infertility
      were enrolled in a prospective randomised double-blind placebo-controlled trial.
      Male participants were randomly assigned to take either one capsule per day of
      the Menevit antioxidant or an identical in appearance placebo for three months
      prior to their partner's IVF cycle. The primary outcome was cleavage stage embryo
      quality and the secondary outcomes were oocyte fertilisation rate, pregnancy
      rates and treatment side-effects. Approval by the local Human Research Ethics
      Committee was obtained prior to the commencement of this study. RESULTS: The
      antioxidant group recorded a statistically significant improvement in viable
      pregnancy rate (38.5% of transferred embryos resulting in a viable fetus at 13
      weeks gestation) compared to the control group (16% viable pregnancy). No
      significant changes in oocyte fertilisation rate or embryo quality were detected
      between the antioxidant and the placebo groups. Side-effects on the Menevit
      antioxidant were rare (8%) and mild in nature. CONCLUSIONS: The Menevit
      antioxidant appears to be a useful ancillary treatment that significantly
      improves pregnancy rates in couples undergoing IVF-ICSI treatment for severe male
      factor infertility.

PMID- 17550490
TI  - Letrozole and desogestrel-only contraceptive pill for the treatment of stage IV
      endometriosis.
AB  - BACKGROUND: It has recently been suggested that aromatase inhibitors may
      effectively reduce pain symptoms related to the presence of endometriosis both in
      postmenopausal women and in subjects of reproductive age. AIMS: This study aims
      to evaluate the effectiveness of a combination of letrozole and desogestrel in
      the treatment of pain symptoms related to the presence of endometriosis. METHODS:
      This open-label prospective study included 12 women with endometriosis-related
      pain symptoms that were refractory to previous medical and surgical treatments.
      All women had previous laparoscopy documenting stage IV endometriosis. The
      treatment protocol included the daily oral administration of letrozole 2.5 mg
      (Femara), desogestrel 75 microg (Cerazette), elemental calcium 1000 mg and
      vitamin D 880 I.U. The scheduled treatment period was six months. RESULTS: None
      of the women included in the study completed the six-month treatment because all
      patients developed ovarian cysts; the median length of treatment was 84 days
      (range, 56-112). At interruption of treatment, all women reported significant
      improvements in dysmenorrhoea and dyspareunia. Pain symptoms quickly recurred at
      three-month follow up. There were no severe adverse effects of treatment; no
      significant change in the mineral bone density was observed during treatment.
      CONCLUSIONS: The combination of letrozole and desogestrel induces a relief of
      pain symptoms in women with endometriosis but it causes the development of
      ovarian cysts. Pain symptoms quickly recur after the completion of treatment.

PMID- 17550491
TI  - A randomised trial of two regimens of vaginal misoprostol to manage termination
      of pregnancy of up to 16 weeks.
AB  - OBJECTIVE: The purpose of this study was to compare the efficacy and side-effects
      of two regimens of vaginal misoprostol for pregnancy termination of up to 16
      weeks. METHODS: A randomised clinical trial of medical pregnancy termination of
      up to 16 weeks was conducted. A hundred pregnant women requesting legal
      termination of pregnancy were randomised into two groups to receive either 200
      microg (50 women) or 400 microg (50 women)--vaginal misoprostol every six hours
      up to four doses. Outcome of abortion and side-effects were assessed. RESULTS:
      The groups were similar in maternal age, gestational age, parity and indication
      for pregnancy termination. There were no statistically significant differences
      between the two groups in abortion (P = 0.084) and mean induction to abortion
      time (P = 0.35). However, the side-effects in the 400 microg group were
      significantly higher than in the 200 microg group (P = 0.000). CONCLUSION: In
      pregnancy termination of up to 16 weeks, 200 microg vaginal misoprostol every six
      hours up to four doses was as effective as 400 microg, but side-effects were more
      common in 400 microg regimen.

PMID- 17550492
TI  - Laparoscopic-assisted vaginal hysterectomy for patients with extensive pelvic
      adhesions: a strategy to minimise conversion to laparotomy.
AB  - AIM: To evaluate a strategy for successful laparoscopic-assisted vaginal
      hysterectomy (LAVH) in patients with extensive pelvic adhesion. METHODS: Two
      hundred and thirty-six patients who underwent LAVH at National Taiwan University
      Hospital were retrospectively enrolled. Twenty-three patients (9.7%) had
      unexpected extensive pelvic adhesions. A special procedure of uterine artery
      preligation through retroperitoneal downstream ureter tracking was applied to
      overcome this problem. The clinical characteristics of the study group were
      analysed. The operative parameters and the outcome were compared between those
      with and without extensive pelvic adhesions. RESULTS: Having extensive adhesions,
      17 patients were associated with endometriosis and the other six were secondary
      to previous Caesarean delivery or pelvic inflammation. The cul-de-sac was
      partially and totally obliterated in 10 and 13 patients, respectively. These 23
      patients had longer operation time (184 vs 146 min, P < 0.05), more blood loss
      (146 vs 89 mL, P < 0.05), but smaller extirpated uteri (278 vs 372 g, P = 0.063),
      compared with the other 213 patients. The average hospital stay was comparable
      (3.2 vs 3.4 days) and there were no ureteral injuries or excessive bleeding. Most
      importantly, not a single case was converted to laparotomy. CONCLUSION: Pelvic
      adhesions of various underlying diseases are associated with increased
      complication and conversion rates during LAVH. Although this technique is not
      new, we believe that the special procedure of uterine artery preligation through
      retroperitoneal downstream ureter tracking may provide a safe approach for
      general gynecologists to complete successful LAVH in patients with unexpected
      extensive pelvic adhesions.

PMID- 17550493
TI  - The impact of chronic vulval pain on quality of life and psychosocial well-being.
AB  - BACKGROUND: Chronic or recurrent pain associated with the female reproductive
      system is not well understood and has been neglected in research, despite it
      being a costly health problem. AIMS: The present research investigated the
      psychosocial impact of vulval pain on health-related quality of life, sexual well
      being, and relationship satisfaction among Australian women. METHODS: Between
      June and December 2004, Australian women with and without vulval pain completed a
      questionnaire containing a range of well-validated self-report measures.
      Questionnaires were returned by 51 women aged between 19 and 68 years with vulval
      pain and 46 women aged between 21 and 65 years without vulval pain. RESULTS:
      Similar to previous research, Australian women with vulval pain reported
      significantly worse health-related quality of life, higher levels of distress
      related to sexual activities, and lower levels of happiness in couple
      relationships than those without pain. CONCLUSIONS: These results highlight
      serious psychosocial implications for women experiencing chronic vulval pain.
      Understanding the impact that vulval pain has on women may assist in developing
      appropriate psychosocial interventions that may improve quality of life.

PMID- 17550494
TI  - The cost of urogynaecological treatments: which are more cost-effective?
AB  - AIMS: To determine the cost-effectiveness of four urogynaecological treatments.
      MATERIALS: Two prospective trials were performed in which 205 women with urinary
      incontinence underwent urogynaecological treatments. The cost incurred and the
      improvement in quality of life (QOL) as a result of treatment was calculated as
      cost/quality-adjusted life year (QALY) and then ranked in order of cost
      effectiveness. RESULTS: The Nurse Continence Advisor (NCA) group (N = 73) and the
      Urogynaecologist (UG) group (N = 72) both had significant improvements in leaks
      per week and incontinence score. QOL improvement was also similar (1.5% vs 1.2%).
      The economic data found a similar improvement in pad usage costs ($A2.90 vs
      $A3.52). The clinician costs were significantly lower for the NCA group ($A60.00
      vs $A105.00) (P < 0.0001). The cost per QALY was significantly lower for the NCA
      group ($A28,009 vs $A35,312) (P = 0.03). Both groups had significant improvements
      in pad testing and leaks per week. The cure/improvement rates were also similar
      at three months (100% vs 89%). There was no significant difference in the
      improvement in QOL between the laparoscopic colposuspension (LC) and open
      colposuspension (OC) groups (2.09% vs 1.54%). The economic data found a similar
      improvement in pad usage costs ($A11.74 vs $A16.17). The theatre costs were
      significantly higher for the LC group ($A403.45 vs $A266.94) (P < 0.0001),
      however the overall costs were significantly lower ($A4,668 vs $A6,124) (P <
      0.0001). The cost/QALY was lower for the LC group ($A63,980 vs $A134,069),
      however this did not reach significance. CONCLUSIONS: Overall, on comparison of
      the cost/QALY's, conservative treatment of urinary incontinence by a NCA was the
      most cost-effective.

PMID- 17550495
TI  - Simultaneous use of a levonorgestrel intrauterine system and an etonogestrel
      subdermal implant for debilitating adolescent endometriosis.
AB  - Adolescent familial endometriosis may cause severe and persistent symptoms that
      are disruptive to lifestyle. Treatment may be difficult in many cases. We
      describe the novel and successful first use of a simultaneous combination of a
      levonorgestrel intrauterine system and an etonogestrel subdermal implant in a
      teenager with severe pain symptoms as a result of laparoscopically confirmed
      endometriosis, which was refractory to other treatments.

PMID- 17550496
TI  - Infracoccygeal sacropexy.
AB  - Fifty-two women with vault prolapse underwent infracoccygeal sacropexy. There was
      a mesh erosion incidence of 21.1% at a mean time of 20 weeks. This rate is higher
      than the rates for single-filament meshes used for suburethral slings. This study
      suggests that multifilament meshes should no longer be used due to the
      unacceptably high erosion rate.

PMID- 17550497
TI  - Immediate post-partum haemorrhage caused by rupture of uterine arteriovenous
      malformation.

PMID- 17550498
TI  - Incidental detection of pigmented lesions in the cervix.

PMID- 17550499
TI  - An unusual case of torsion hydrosalpinx after hysterectomy: a case report.

PMID- 17550500
TI  - Re: Alternative cervical cancer prevention in low-resource settings: experiences
      of visual inspection by acetic acid with single-visit approach in the first five
      provinces of Thailand.

PMID- 17550501
TI  - Re: Customised birthweight: coefficients for an Australian population and
      validation of the model.

PMID- 17550503
TI  - Translabyrinthine surgery for disabling vertigo in vestibular schwannoma
      patients.
AB  - OBJECTIVE: To determine the impact of translabyrinthine surgery on the quality of
      life in vestibular schwannoma patients with rotatory vertigo. STUDY DESIGN:
      Prospective study in 18 vestibular schwannoma patients. SETTING: The study was
      conducted in a multispecialty tertiary care clinic. PARTICIPANTS: All 18 patients
      had a unilateral intracanalicular vestibular schwannoma, without serviceable
      hearing in the affected ear and severely handicapped by attacks of rotatory
      vertigo and constant dizziness. Despite an initial conservative treatment,
      extensive vestibular rehabilitation exercises, translabyrinthine surgery was
      performed because of the disabling character of the vertigo, which considerably
      continued to affect the patients' quality of life. MAIN OUTCOME MEASURES:
      Preoperative and postoperative quality of life using the Short Form 36 Health
      Survey (Short Form-36) scores and Dizziness Handicap Inventory (DHI) scores.
      RESULTS: A total of 17 patients (94%) completed the questionnaire preoperatively
      and 3 and 12 months postoperatively. All Short Form-36 scales of the studied
      patients scored significantly lower when compared with the healthy Dutch control
      sample (P < 0.05). There was a significant improvement of DHI total scores and
      Short Form-36 scales on physical and social functioning, role-physical
      functioning, role-emotional functioning, mental health and general health at 12
      months after surgery when compared with preoperative scores (P < 0.05).
      CONCLUSIONS: Vestibular schwannoma patients with disabling vertigo, experience
      significant reduced quality of life when compared with a healthy Dutch
      population. Translabyrinthine tumour removal significantly improved the patients'
      quality of life. Surgical treatment should be considered in patients with small-
      or medium-sized tumours and persisting disabling vertigo resulting in a poor
      quality of life.

PMID- 17550504
TI  - Systemic high blood pressure and inner ear dysfunction: a preliminary study.
AB  - OBJECTIVE: To assess the association between inner ear dysfunction and retinal
      vascular changes related to systemic arterial hypertension. DESIGN: A
      comparative, cross-sectional and observational study. SETTING: Primary care. MAIN
      OUTCOMES MEASURES: Hearing and vestibular symptoms evaluated by a standardized
      questionnaire; cochlear function evaluated by audiometry and distortion product
      otoacoustic emissions; vestibular function evaluated by oculomotor and bithermal
      caloric tests and vascular retinal compromise evaluated by ophthalmoscopy
      (according to the modified Scheie classification). RESULTS: Forty-two subjects
      participated in the study, 21 with and 21 without arterial hypertension, age and
      sex matched; with no history of diabetes mellitus and with normal glucose levels
      and normal blood lipids. Although patients with hypertension reported vertigo
      more frequently than control subjects, conventional oculomotor and bithermal
      caloric tests showed no difference between the two groups. Patients with
      hypertension showed deterioration of hearing thresholds at 8 kHz and, compared
      with normotensive subjects, a higher frequency of abnormal otoacoustic emissions
      (P = 0.01). According to Scheie classification, 43% (95% CI: 33-53%) of the
      patients showed second degree retinal vascular compromise and 24% (95% CI: 15
      33%) of them showed first degree compromise. The degree of the vascular retinal
      compromise was significantly correlated with the hearing thresholds at 8 kHz
      (Spearman's correlation coefficient 0.45, P = 0.002) and it was also consistent
      with the absence of otoacoustic emissions at frequencies between 4 and 8 kHz.
      CONCLUSION: The results of this preliminary study suggest that patients with
      systemic arterial hypertension may have cochlear dysfunction associated with the
      vascular disease because of hypertension, which could be silent and without clear
      evidence of vestibular dysfunction.

PMID- 17550505
TI  - Primary hyperparathyroidism: do perioperative biochemical variables correlate
      with parathyroid adenoma weight or volume?
AB  - OBJECTIVES: To investigate the relationship between clinical variables and
      biochemical markers of calcium homeostasis and parathyroid adenoma size, in
      patients undergoing surgery for primary hyperparathyroidism. To determine the
      potential clinical utility of the findings in preoperative planning and
      prediction of postoperative hypocalcaemia. DESIGN: Retrospective data analysis.
      PARTICIPANTS: Ninety-two patients treated surgically for primary
      hyperparathyroidism caused by a solitary parathyroid adenoma between 1996 and
      2006. MAIN OUTCOME MEASURES: Complete data was obtained for 77 participants
      including patient demographics, perioperative calcium, parathyroid hormone and
      phosphate levels, adenoma weight and histological dimensions. Multiple and binary
      logistic regression analyses were used to investigate the relationship between
      clinical and biochemical variables and adenoma weight and volume. Similar
      analysis was used to identify predictors of postoperative hypocalcaemia. SETTING:
      University Teaching Hospital Otolaryngology Department. RESULTS: The mean age at
      presentation was 59 years. The mean preoperative calcium and PTH levels were 2.86
      +/- 0.2 mmol/L and 17.2 +/- 12.3 ng/L, respectively, falling to 2.3 +/- 0.01 and
      4.1 +/- 2.7 postoperatively. The mean adenoma weight was 1.71 +/- 1.41 g. No
      correlation existed between clinical variables and preoperative biochemical
      markers of calcium homeostasis and adenoma weight or volume. There was a weak
      correlation between the preoperative to postoperative change in calcium and PTH
      levels {[deltaCa(2)+] vs. [deltaPTH]} (r = 0.24; P < 0.05) but no predictors of
      postoperative hypocalcaemia could be identified. CONCLUSIONS: Biochemical
      parameters will not accurately predict the size of a parathyroid adenoma. The
      size of a parathyroid adenoma does not correlate with postoperative calcium
      levels and is therefore not useful as a predictor of postoperative hypocalcaemia.

PMID- 17550506
TI  - Photodynamic therapy in the treatment of multiple primary tumours in the head and
      neck, located to the oral cavity and oropharynx.
AB  - OBJECTIVES: Multiple primary tumours are a common problem in the head and neck
      cancer patients. Curative surgery or radiotherapy of these tumours can be very
      mutilating or even impossible. This study aims at evaluating meta-tetrahydroxy
      phenyl chlorin-mediated photodynamic therapy for second or multiple primary
      tumours in the head and neck. DESIGN: Retrospective study of all patients with
      second or multiple primary tumours treated by photodynamic therapy over a 10-year
      period. SETTING: All patients were treated in the Netherlands Cancer Institute, a
      tertiary referral centre for the head and neck cancer patients. PARTICIPANTS: A
      total of 27 patients with 42 the second or the multiple primary head and neck
      tumours were treated by photodynamic therapy (0.15 mg/kg meta-tetrahydroxy-phenyl
      chlorin). MAIN OUTCOMES MEASURES: Cure rates. RESULTS: Twenty-eight of 42 tumours
      were cured (67%). Cure rates for stage I or in situ disease were 85%versus 38%
      for stage II/III. CONCLUSIONS: Cure rates for photodynamic therapy of the
      multiple primary head and neck tumours were lower than previously described for
      first primaries, but were still very encouraging for this difficult patient
      population. The high cure rate obtained in stage I multiple primaries emphasises
      the importance of a meticulous follow-up of patients treated for the head and
      neck cancer to detect new tumours at a curable stage.

PMID- 17550507
TI  - A child with recurrent acute otitis media.

PMID- 17550512
TI  - Silver nitrate cauterisation, does concentration matter?
AB  - Epistaxis from the anterior septum is frequently treated with a topical
      application of silver nitrate. There are two concentrations commercially
      available and in use by otolaryngologists, these are 75% and 95% silver nitrate.
      The purpose of the present study was to investigate the histological effect of
      the two different silver nitrate concentrations on mucosal tissue at a fixed
      contact time of 5 s. Twelve children undergoing routine tonsillectomy were
      included in this study. Prominent blood vessels on the mucosal surface of the
      tonsils were identified and a single vessel on each tonsil was selected for
      application of either 75% or 95% concentration of silver nitrate for 5 s. Depth
      of penetration across the tonsil tissue was measured following application of the
      two different silver nitrate concentrations. This study demonstrated a
      significant difference in depth of tissue penetration with the 95% averaging a
      twofold increase in penetration depth. It is likely that the increased depth of
      penetration with 95% silver nitrate may increase the risk of complication of
      nasal cautery such as septal perforation, particularly in patients undergoing
      repeated or bilateral nasal cautery.

PMID- 17550513
TI  - Derevator: a soft tissue elevator for maxillary sinus in endoscopic sinus
      surgery.
AB  - Removal of the soft tissue lesions from the maxillary sinus is sometimes
      difficult and time consuming in endoscopic sinus surgery. Failure of endoscopic
      removal may necessitate combination of canine fossa approach and endoscopic
      approach. Our new instrument, 'Derevator', is designed for easy removal of the
      pathological soft tissue lesions from the maxillary sinus through middle meatal
      antrostomy. Derevators are available for both adults and children. Suction-tipped
      ones are also available.

PMID- 17550514
TI  - A technique for the orientation of endoscopically resected laryngeal lesions.
AB  - Endoscopic resection is a widely accepted method of treating early laryngeal
      malignancies. Accurate histological assessment of resected laryngeal specimens
      can be difficult due to their small size and potential damage and distortion
      caused by standard orientation and processing techniques. A new technique is
      described which employs dehydrated cucumber to mount laryngeal specimens for
      orientation and processing. This technique is quick, easy, cheap and reliable,
      allowing accurate histological assessment of potentially malignant lesions.
      Better orientating and processing of laryngeal specimens can optimise treatment
      decisions based on histological results.

PMID- 17550515
TI  - Antimicrobial prophylaxis in otorhinolaryngology/head and neck surgery.
AB  - Prophylactic antimicrobial therapy is defined as the administration of an
      antimicrobial agent prior to contamination of previously sterile tissues or
      fluids, in an attempt to reduce the microbial burden of intraoperative
      contamination. Prophylactic antimicrobial therapy should cover the anticipated
      floral contamination, with therapeutic levels from incision to closure. There is
      level I evidence to support the use of prophylaxis in clean-contaminated head and
      neck procedures and tonsillectomy, while level II evidence fails to support the
      use of prophylaxis in clean head and neck procedures. The aim of this study was
      to evaluate the use, timing and appropriateness of antimicrobial prophylaxis
      perioperatively, in otorhinolaryngological/head and neck procedures. A total of
      34/51 (66%) patients were administered antimicrobial agents prophylactically. Six
      of 19 patients (42%) who ought to have received prophylaxis did not, while six of
      13 (46%) of those who did not require it received it. Administration was
      unsuitably timed in 14 of 34 (41%) operations. This study demonstrates
      unnecessary administration of antimicrobial agents perioperatively, subclinical
      intraoperative antimicrobial levels for prophylaxis and inconsistent
      documentation regarding prophylaxis in otorhinolaryngological/head and neck
      procedures in a general ENT unit.

PMID- 17550516
TI  - Lesson plans in surgical training.
AB  - Lesson plans in surgery enable trainers and trainees to agree on goals that
      balance training needs with service commitments. Lesson plans are individualised
      to the trainee and encourage ownership of learning. They are based on SMART
      criteria and therefore have a sound educational footing. Most of the work in
      creating a lesson plan falls to the trainee. The total time for creation of each
      plan is approximately 20 min. Our use of lesson plans for surgical training has
      been met with favourable response from both trainer and trainees.

PMID- 17550517
TI  - A third hand for nasal cautery.

PMID- 17550518
TI  - Diagrammatic recording of tympanomastoid procedures.

PMID- 17550521
TI  - Consent issues with the National Prospective Tonsillectomy Audit: the Oxford
      experience.

PMID- 17550522
TI  - The practice of otolaryngologists inserting percutaneous gastrostomies in England
      and Wales.

PMID- 17550523
TI  - The 'Ic and Glic Pope Wick'.

PMID- 17550524
TI  - Nasal septum loop technique for securing naso-gastric tube.

PMID- 17550525
TI  - Pharyngoesophageal foreign bodies: a report of 10-year experience.

PMID- 17550526
TI  - ENT referrals to the neurology clinic.

PMID- 17550527
TI  - Hydrogen peroxide mouthwash in post-tonsillectomy haemorrhage.

PMID- 17550528
TI  - Career choices in otolaryngology: implications for modernising medical careers.

PMID- 17550529
TI  - Warning - ward-based treatment rooms increase risk in ENT emergency practice.

PMID- 17550530
TI  - In search of a better clinic letter for general practitioners.

PMID- 17550531
TI  - Conservative management of recurrent nasal squamous papilloma with topical
      immunomodulators.

PMID- 17550532
TI  - Masters degrees for ENT trainees.

PMID- 17550533
TI  - Addressing the challenges of genetic screening for deafness.

PMID- 17550551
TI  - Thiazolidinediones in dermatology.
AB  - Thiazolidinediones, also known as glitazones, represent a relatively new class of
      medication used for glycemic control in patients with type II diabetes mellitus.
      These drugs interact with the peroxisome proliferator-activated receptor gamma, a
      member of the nuclear receptor superfamily, which in turn heterodimerizes with
      retinoid X receptors to stimulate gene transcription. At a physiologic level,
      glitazones stimulate adipocyte differentiation, enhance insulin-sensitive glucose
      uptake by muscle and fat cells, suppress angiogenesis, inhibit tumor cell growth,
      and normalize keratinocyte differentiation. They have also demonstrated the
      capacity to diminish inflammatory cytokine production, most notably, that of
      tumor necrosis factor alpha. Patients with such disparate conditions as
      psoriasis, hirsutism, melanoma, angiosarcoma, lipodystrophy, and necrobiosis
      lipoidica have benefited from the administration of thiazolidinediones.
      Clinicians should become familiar with glitazones as they are experiencing a
      burgeoning use among patients with non-insulin-dependent diabetes mellitus and
      have demonstrated clinical efficacy in treating certain skin conditions.

PMID- 17550552
TI  - Malignant melanoma and nonmelanoma skin cancers in Northrhine-Westphalia,
      Germany: a patient- vs. diagnosis-based incidence approach.
AB  - BACKGROUND: Dermatologists have repeatedly criticized that the public health
      importance of nonmelanoma skin cancers is not appropriately reflected by the
      patient-based cancer incidence rates of population-based cancer registries. The
      aims of this study were to estimate the patient incidence rates of squamous cell
      carcinoma (SCC), basal cell carcinoma (BCC), and skin melanoma, and to study the
      effect of multiple primary skin tumors on the incidence rates. METHODS: We used a
      network of physicians covering a population of about 75,000 individuals to
      register all newly diagnosed invasive skin cancers (996 diagnoses in 796
      patients), including BCC, SCC, and skin melanoma, from July 1998 to June 2003. We
      calculated age-standardized (world standard population) incidence rates (cases
      per 100,000 person-years) for the first diagnoses (called "patient incidence")
      and for any diagnoses of BCC, SCC, and skin melanoma (called "case incidence").
      RESULTS: The patient incidence rates of BCC were 63.6 in men and 54.0 in women,
      and the case incidence rates of BCC were 82.7 and 71.1, respectively. The patient
      incidence rates of SCC were 17.4 in men and 9.7 in women, and the case incidence
      rates were 20.4 and 10.2, respectively. The patient and case incidence rates of
      skin melanoma were about the same at 13.6 in men and 18.5 in women. Twenty-five
      per cent of the BCC patients and 14% of the SCC patients suffered from more than
      one BCC and SCC, respectively, during the 5-year period. CONCLUSIONS: Patient
      incidence rates of BCC and SCC substantially underestimate the burden of
      nonmelanoma skin cancer in the population.

PMID- 17550553
TI  - Acute febrile neutrophilic dermatosis (Sweet's syndrome): a study of 15 cases in
      Iran.
AB  - BACKGROUND: Sweet's syndrome is well recognized by dermatologists and is not
      infrequently diagnosed in Iran; however, few case series have been reported.
      METHODS: A clinicopathologic study was carried out on 15 cases of Sweet's
      syndrome in Hamedan, in the west of Iran, between 1994 and 2004. RESULTS: The
      incidence of Sweet's syndrome was 3 per 10,000 amongst new dermatologic patients.
      All were women with a mean age of 58 years. All 15 cases were of the classic
      type, with no associated diseases. Fever was seen in only six (40%) patients.
      CONCLUSIONS: Sweet's syndrome has a broad spectrum of clinical and pathologic
      findings in various areas of the world. Further investigation is necessary to
      determine the etiology and effect of environmental factors in this disease.

PMID- 17550554
TI  - Patient education and regular surveillance results in earlier diagnosis of second
      primary melanoma.
AB  - BACKGROUND: As the incidence of cutaneous melanoma continues to rise, more
      individuals will be at risk for developing second primary melanomas. We
      hypothesize that patient education and follow-up surveillance will lead to the
      early detection of subsequent primary melanomas as demonstrated by a decrease in
      Breslow thickness at diagnosis. METHODS: A computer-based investigation was
      performed to identify patients who had developed a second primary melanoma
      following treatment of in situ and American Joint Commission on Cancer (AJCC)
      Stage I or II melanoma. Patients are routinely educated on the increased risk of
      developing a second primary lesion and characteristic clinical features of
      melanoma. Patient surveillance was performed on a regular basis. Differences in
      Breslow thickness between the initial and subsequent primary melanomas were
      analyzed by a paired t-test. RESULTS: Among 877 individuals identified in the
      Mount Sinai School of Medicine Department of Dermatopathology database with in
      situ or AJCC Stage I or II melanoma, 111 developed a second primary melanoma. The
      mean thickness was 0.239 +/- 0.661 mm for the initial melanoma and 0.1135 +/-
      0.319 mm for the subsequent melanoma. By paired t-test, the difference in tumor
      thickness was statistically significant (P = 0.019). CONCLUSIONS: Upon analysis
      of our data, subsequent primary cutaneous melanomas were found to be
      significantly thinner than initial primary melanomas at the time of diagnosis.
      This suggests that earlier diagnosis may be the result of patient education and
      careful follow up. Counselling on the risk of developing a second primary
      melanoma, education regarding clinical characteristics of melanoma, and routine
      lifelong follow up should be provided to all patients diagnosed with a cutaneous
      melanoma.

PMID- 17550555
TI  - Diagnostic value of Vbeta2-positive T-cell expansion in toxic shock syndrome.
AB  - BACKGROUND: diagnostic dilemma in toxic shock syndrome (TSS) is that the results
      of microbiologic investigations are often not available immediately because of
      the need for incubation, or no obvious entry point can be found. METHODS: We
      describe three patients with a clinical diagnosis of TSS in whom microbiologic
      tests were negative. RESULTS: All patients had complicated courses with
      vasopressor-dependent shock, renal and respiratory failure, and disseminated
      intravascular coagulation for at least 1 week. In all three patients, diagnosis
      was considerably faster with the assessment of the expansion of T-cell-receptor
      Vbeta2-positive T cells (> 15%) than by Centers for Disease Control and
      Prevention (CDC) diagnosis, because of the complicated clinical picture or the
      delay caused by waiting for the results of microbiologic investigations.
      CONCLUSIONS: Our results indicate that diagnostic procedures incorporating Vbeta2
      positive T cells could be a useful tool for the diagnosis of TSS.

PMID- 17550556
TI  - Brooke-Spiegler syndrome - report of four families: treatment with CO2 laser.
AB  - BACKGROUND: Brooke-Spiegler syndrome is a well known but rare cutaneous disorder
      characterized by the presence of multiple trichoepitheliomas and cylindromas.
      METHODS: Four families with Brooke-Spiegler syndrome are described. RESULTS:
      Spiradenomas developed on the back in two patients. A CO(2) laser was used to
      treat facial trichoepitheliomas in two patients with good results. CONCLUSIONS:
      The large number of facial lesions in this syndrome often produce a significant
      emotional impact. We believe that it is important to provide patients with a good
      therapeutic option. CO(2) laser therapy may fill this role.

PMID- 17550557
TI  - Physiological effects of ultrasound mist on fibroblasts.
AB  - BACKGROUND: Chronic wounds present an increasing challenge in healthcare and
      consume a substantial portion of healthcare cost. Although new treatments have
      been developed, treatment success has not been improved greatly. Ultrasound has
      long been employed in medicine. Its unique ability to deliver energy makes it an
      ideal candidate as a wound care modality. We proposed that ultrasound would
      differentially affect intracellular signaling pathways and, with the ability to
      assess this effect using a noncontact form of ultrasound, were provided with a
      means to test this proposal. METHODS: The cellular morphology, mitogenic
      activities, expression of keratinocyte growth factor (KGF) and transforming
      growth factor beta-1 (TGF-beta1), and activation of extracellular regulated
      kinase (ERK) and c-Jun N-terminal kinase (JNK) signaling pathways of dermal
      fibroblasts were studied after ultrasound treatment. Untreated and scrape-wounded
      fibroblasts were utilized as controls. RESULTS: There was no difference in
      morphology observed, except for vacuolization in ultrasound-treated fibroblasts.
      Mitogenic activities were similar between ultrasound-treated and scrape-wounded
      fibroblasts. Ultrasound-treated fibroblasts exhibited a much earlier increase in
      KGF expression, ERK activation, and JNK activation. The ERK/JNK ratio was
      increased markedly in ultrasound-treated fibroblasts. CONCLUSION: We conclude
      that ultrasound induces cellular responses that may be beneficial to wound
      healing.

PMID- 17550558
TI  - Clinical patterns of sexually transmitted diseases, associated sociodemographic
      characteristics, and sexual practices in the Farwaniya region of Kuwait.
AB  - BACKGROUND: Sexually transmitted diseases (STDs) are common worldwide, but there
      are few studies available on STDs from the Gulf countries, including Kuwait. Our
      goal was to determine the clinical patterns, sociodemographic factors, and sexual
      practices of patients with STDs who attended a government hospital in the
      Farwaniya region of Kuwait. METHODS: All patients seen over a 1-year period (July
      2003 to June 2004), who presented with signs and symptoms suggestive of STDs,
      were included. Sociodemographic details and clinical findings were recorded. The
      diagnosis of each STD was based mainly on standard World Health Organization
      (WHO) criteria and available data. Serologic tests for syphilis and human
      immunodeficiency virus (HIV) were offered to all patients. RESULTS: One thousand
      and ninety-six patients (1068 male, 28 female) with STDs constituted 2.84% of all
      new dermatology patients seen; most (866) were in the 21-40-year age group. The
      STDs were acquired from commercial sex workers in 844 patients (77%).
      Heterosexual encounter (99.3%) was the most common mode of acquiring STDs.
      Urethral discharge was noted in 54.1% of patients, followed by genital ulcers
      (17.8%), papules/growths (16.4%), and urethral/pubic pain without associated
      discharge/ulcers (5.9%); these were the four most common presenting complaints.
      Evaluation revealed gonorrhea in 31.5% of patients, nongonococcal urethritis in
      23.6%, chlamydia in 4.1%, nonspecific urethritis in 19.5%, concomitant gonorrhea
      and chlamydia urethritis in 2.7%, genital warts in 13.7%, chancroid in 13.0%,
      genital herpes in 4.8%, molluscum contagiosum in 2.7%, and lymphogranuloma
      venereum in 1.4%. CONCLUSIONS: Urethral discharge, gonorrhea, and nonspecific
      urethritis (presenting with urethral discharge), followed by genital warts,
      chancroid, and genital herpes (ulcers), were the most common STDs among male
      patients in the Farwaniya region of Kuwait. Although no case of HIV or syphilis
      was detected, health authorities and physicians need to remain vigilant.

PMID- 17550559
TI  - Otorhinolaryngologic manifestations of leprosy.

PMID- 17550560
TI  - Chagas' disease reactivation with skin symptoms in a patient with kidney
      transplant.
AB  - Immunodepressed patients in the intermediate phase of Chagas' disease may undergo
      reactivation of the disease together with atypical symptoms. The case of an
      immunodepressed kidney transplant patient with reactivation of Chagas' disease
      with skin symptoms is reported. A 65-year-old man presented with infiltrated
      erythematous lesions on the anterior aspect of the right thigh of 2 weeks'
      duration. The lesions later extended to the abdomen, thorax, and lower limbs. In
      the histologic skin examination, amastigotes and Trypanosoma cruzi
      trypoamastigotes were observed. A fresh smear showed positive parasitemia. Using
      the Strout hemoconcentration method, multiple Trypanosoma cruzi trypoamastigotes
      with motility could be seen. Polymerase chain reaction was positive for
      Trypanosoma cruzi. An immunofluorescence test was positive (1 : 64) and there was
      hemoagglutination (1 : 32). Treatment was started with benznidazole, 7 mg/kg/day.
      The patient did not evolve favorably and died 20 days after hospitalization. Skin
      lesions may be a manifestation of the reactivation of Chagas' disease in
      immunosuppressed patients. All patients with positive Chagas' serology who
      require immunosuppressant drugs should receive specific treatment for Chagas'
      disease.

PMID- 17550561
TI  - Nevus lipomatosus cutaneous superficialis with angiokeratoma.

PMID- 17550562
TI  - Carcinoma erysipeloides associated with breast carcinoma.

PMID- 17550563
TI  - Urachal duct remnant-like umbilical clear cell acanthoma in an infant: an unusual
      presentation and pitfall in clinical practice.
AB  - BACKGROUND: Although an umbilical nodule is common in neonates and young infants,
      an umbilical nodule of poor therapeutic response will increase the likelihood of
      other uncommon etiology. Clear cell acanthoma (CCA) has never been described as
      an oozing umbilical nodule on infants. METHODS: To present a case of CCA which
      occurred on an 8-month-old female infant presenting with one weeping nodule on
      the umbilicus since early neonate. The lesion underwent skin biopsy and
      subsequent hematoxylin-eosin and periodic acid-Schiff staining. RESULT: Three
      courses of liquid nitrogen cryosurgery were performed after the diagnosis of CCA
      was confirmed. The lesion resolved rapidly. CONCLUSION: This report presents the
      first and youngest case of umbilical CCA in the English literature. This case
      supports the inflammatory dermatosic nature of CCA.

PMID- 17550564
TI  - Intravascular large cell lymphoma.

PMID- 17550565
TI  - Coexisting pseudoxanthoma elasticum and lupus erythematosus: report of two cases.
AB  - Pseudoxanthoma elasticum (PXE) is a heritable connective tissue disorder
      affecting the elastic structures in the body, manifesting with cutaneous,
      ophthalmologic and cardiovascular findings. The association of PXE and systemic
      disease is rare, as only six cases have been reported in the literature. We
      describe herein two cases of coexisting PXE and cutaneous lupus and discuss a
      possible association. Although a fortuitous association cannot be excluded, the
      calculated prevalence of the association in our area was much less than in our
      observation. Given the ocular and vascular complications of PXE, clinicians who
      treat patients with lupus should be aware of this possible association.

PMID- 17550566
TI  - Cutaneous phaeohyphomycosis caused by Veronaea botryosa observed as sclerotic
      cells in tissue.

PMID- 17550567
TI  - Cutaneous leishmaniasis reactivation 2 years after treatment caused by systemic
      corticosteroids - first report.
AB  - American tegumentary leishmaniasis (ATL), an endemic anthropozoonosis in various
      countries in the world, is caused by parasites of the genus Leishmania. Despite
      reports on ATL reactivation as a result of immunosuppression, to the best of our
      knowledge, this paper describes the first case of ATL reactivation in its
      localized form (cutaneous leishmaniasis) associated with the administration of
      systemic corticosteroids. The possible action of corticosteroids on the host
      immune response to the parasite in patients with localized cutaneous
      leishmaniasis is discussed. This report demonstrates the possibility of ATL
      reactivation in patients using corticosteroids, an observation that should be
      considered in individuals treated with this medication.

PMID- 17550568
TI  - Anhidrotic ectodermal dysplasia with palmoplantar keratoderma: an unusual
      presentation.
AB  - Anhidrotic ectodermal dysplasia (AED), or Christ-Siemens-Touraine syndrome, was
      first described in 1848 by Thurnam. It is characterized by a partial or complete
      absence of sweat glands, hypotrichosis and hypodontia. The mode of inheritance is
      predominantly X-linked but an autosomal recessive pattern has also been
      observed.(2) Palmoplantar keratoderma is classically a component of hidrotic
      ectodermal dysplasia; however, we report herein two brothers who had classical
      manifestations of AED along with palmoplantar keratoderma.

PMID- 17550569
TI  - Giant onychomatricoma: report of two cases with rare clinical presentation.
AB  - BACKGROUND: Onychomatricoma was reported for the first time by Baran and Kint as
      a rare nail matrix tumor with specific clinical and histologic features,
      including a macroscopic appearance of filiform digitations originating from the
      nail matrix which are inserted in the nail plate.(1) The appearance of the lesion
      may resemble that of an "anemone." All previous reports have been mostly from
      Europe, with only one case from North America. These are the first case reports
      from Mexico. They show rare clinical characteristics, in particular tumor
      involving the entire nail matrix. METHODS: Two cases are presented: Case 1, a 59
      year-old man with a 2-year history of deformity of the entire nail apparatus of
      the right thumb, clinically suggestive of onychomatricoma; Case 2, a 45-year-old
      woman with a 3-year history of gradual nail dystrophy, initially misdiagnosed as
      onychomycosis and treated unsuccessfully for several months with antimycotics by
      a general physician. In both cases, the entire nail plate was affected and,
      because of the clinical appearance, nail exploration and excisional biopsy of the
      tumors at the nail matrix were performed. RESULTS: During nail matrix surgical
      exploration, including avulsion of the nail plate, characteristic digitiform
      projections that were firmly attached to the nail plate were observed. In both
      cases, the entire nail matrix was affected, producing a giant form of
      onychomatricoma. Hematoxylin and eosin stain showed characteristic filiform
      projections that corresponded to the clinical appearance, with elongated
      epithelium from the nail matrix and fibromyxoid stroma with multiple basophilic
      cells, and typical clefts in between. CONCLUSIONS: Onychomatricoma has a
      classical clinical appearance; however, it is difficult to identify, as it is not
      until surgery, when the typical filiform projections are more visible, that the
      diagnosis can be made. Onychomatricoma is a rare tumor. The involvement of the
      entire nail matrix, with secondary nail dystrophy, in both cases presented here
      makes them interesting case reports of this unusual form of tumor.

PMID- 17550570
TI  - Transitioning patients from efalizumab to alternative psoriasis therapies:
      findings from an open-label, multicenter, Phase IIIb study.
AB  - BACKGROUND: Rebound in psoriasis is, by definition, a rapid worsening of disease
      following the discontinuation of therapy for psoriasis; it occurs following the
      abrupt discontinuation of many therapies. To prevent rebound on discontinuation
      of efalizumab, this study evaluated the effectiveness of transitioning patients
      to an alternative psoriasis therapy. METHODS: Patients (n = 130) received
      subcutaneous efalizumab 1 mg/kg/week for 12 weeks. Efalizumab was discontinued at
      12 weeks; patients were evaluated for improvement from baseline in the Psoriasis
      Area and Severity Index (PASI) and a 12-week transition period was begun.
      Patients who achieved PASI improvement of 75% or more (PASI-75) at week 12 of
      efalizumab treatment were observed during the transition period and treated only
      if psoriasis recurred. Patients who did not attain PASI-75 at week 12 of
      efalizumab treatment were immediately transitioned to an alternative psoriasis
      therapy at the physician's discretion. All patients were evaluated for signs of
      rebound following efalizumab discontinuation. RESULTS: Rebound was not observed
      in any PASI-75 responder (n = 46). Rebound was observed in two of 32 patients who
      achieved between PASI-50 and PASI-75, and was more common in nonresponders
      (14/49). Rebound was observed in none of the eight patients treated with
      cyclosporine and in two of the 12 patients treated with methotrexate during the
      transition period. CONCLUSIONS: These results suggest that efalizumab-responsive
      patients are less likely to experience rebound than nonresponders and may not
      require treatment until disease recurrence following efalizumab discontinuation.
      Efalizumab nonresponders are at higher risk of developing rebound and thus should
      be considered for transition to an appropriate psoriasis therapy immediately
      following efalizumab discontinuation.

PMID- 17550571
TI  - Nontuberculous mycobacteria infection after mesotherapy: preliminary report of 15
      cases.
AB  - BACKGROUND: Mesotherapy is an increasingly used technique which is currently
      causing several mycobacterial infections owing to contaminated substances being
      injected, and also to poor aseptic measures being held by nonprofessional
      practitioners. PATIENTS AND METHODS: We collected 15 cases of nontuberculous
      mycobacteria (NTM) infection after mesotherapy in a 6-month period. RESULTS: All
      patients were female with ages ranging from 19 to 52 years; the main substances
      injected were procaine and lecithin, and the time between mesotherapy and the
      appearance of the lesions varied between 1 and 12 weeks. Clinical lesions were
      mostly nodules and abscesses, which were localized in the abdomen and buttocks in
      the majority of cases. The main patient complaint was local pain but some
      presented with systemic symptoms such as fever and malaise. Biopsies reported
      granulomatous chronic inflammation in the majority of cases. Skin cultures were
      positive for NTM and Mycobacterium chelonae. DISCUSSION AND CONCLUSIONS:
      Mesotherapy not performed with quality controlled substances can be a
      predisposing factor for NTM infection.

PMID- 17550572
TI  - DRESS syndrome caused by teicoplanin and vancomycin, associated with reactivation
      of human herpesvirus-6.

PMID- 17550573
TI  - "Unknown Risks" of non-steroid topical medications for atopic dermatitis.
AB  - INTRODUCTION: Tacrolimus ointment is a nonsteroid treatment for atopic dermatitis
      which is both effective and has a minimal side-effect profile. However, some
      clinicians may be reluctant to use tacrolimus ointment due to the "unknown
      risks", meaning those that have not been uncovered in human studies conducted
      thus far. Therefore, the available animal data regarding the "unknown risks" of
      topical tacrolimus therapy are reviewed, and a discussion of the interpretation
      of this available but limited data is presented. ANIMAL STUDIES: Some of the fear
      on the part of clinicians regarding the use of topical tacrolimus may come from
      the results of animal studies which showed an increase in lymphoma and UV-induced
      skin cancer after treatment with topical tacrolimus in animal models of
      carcinogenesis. However, rigorous assessment of these studies suggest that it is
      somewhat likely that these represent a species-specific response to tacrolimus in
      an animal already predisposed to tumor formation, and therefore may not be
      relevant in assessing the possibility of an increased human health risk.
      CONCLUSIONS: Animal and human studies suggest that topical tacrolimus is a safe
      alternative to topical steroids, with the major known adverse effect being a
      transient burning sensation, compared with the known adverse effects of topical
      steroids, including long-lasting ones. Therefore, in the opinion of the authors,
      currently available data, including animal studies, does not suggest that
      "unknown risks" of topical tacrolimus need be any more concerning than the known
      side-effects of the topical steroids.

PMID- 17550574
TI  - Iran's contribution to the dermatology literature.

PMID- 17550575
TI  - A downturn in the incidence of head lice infestation?

PMID- 17550576
TI  - Lymphedematous areas: privileged sites for tumors, infections, and immune
      disorders.

PMID- 17550578
TI  - Do maternal cells trigger or perpetuate autoimmune diseases in children?
AB  - The placental barrier is not the impenetrable wall that it was once presumed to
      be. During pregnancy, fetal cells pass into the mother, where they persist for
      decades after the pregnancy, leading to fetal microchimerism (FMc). Maternal
      cells also pass into the fetus, where they can persist long after birth of the
      child into adulthood, leading to maternal microchimerism(MMc). FMc and MMc
      represent foreign cells, and thus have been implicated in the pathogenesis of
      autoimmune diseases that resemble graft-versus-host disease after stem cell
      transplantation. FMc, hypothesized to contribute to the high predisposition of
      autoimmune diseases in women, has been reviewed recently. In patients who have
      never been pregnant, (children, males, and nulliparous females), MMc may
      represent the foreign cells that initiate or perpetuate chronic inflammatory
      disease.

PMID- 17550579
TI  - A peripatetic pediatrician's journey into pediatric rheumatology.
AB  - Earl Brewer discusses his journey into pediatric rheumatology from 1958 to
      retirement in 1990 in three parts.

PMID- 17550580
TI  - Skeletonization of radial and gastroepiploic conduits in coronary artery bypass
      surgery.
AB  - The use of a skeletonized internal thoracic artery in coronary artery bypass
      graft surgery has been shown to confer certain advantages over a traditional
      pedicled technique, particularly in certain patient groups. Recent reports
      indicate that radial and gastroepiploic arteries can also be harvested using a
      skeletonized technique. The aim of this study is to systematically review the
      available evidence regarding the use of skeletonized radial and gastroepiploic
      arteries within coronary artery bypass surgery, focusing specifically on it's
      effect on conduit length and flow, levels of endothelial damage, graft patency
      and clinical outcome. Four electronic databases were systematically searched for
      studies reporting the utilisation of the skeletonization technique within
      coronary revascularisation surgery in humans. Reference lists of all identified
      studies were checked for any missing publications. There appears to be some
      evidence that skeletonization may improve angiographic patency, when compared
      with pedicled vessels in the short to mid-term. We have found no suggestion of
      increased complication rates or increased operating time. Skeletonization may
      increase the length of the conduit, and the number of sequential graft sites, but
      no clear clinical benefits are apparent. Our study suggests that there is not
      enough high quality or consistent evidence to currently advocate the application
      of this technique to radial or gastroepiploic conduits ahead of a traditional
      pedicled technique.

PMID- 17550581
TI  - The genetic study of three population microisolates in South Tyrol (MICROS):
      study design and epidemiological perspectives.
AB  - BACKGROUND: There is increasing evidence of the important role that small,
      isolated populations could play in finding genes involved in the etiology of
      diseases. For historical and political reasons, South Tyrol, the northern most
      Italian region, includes several villages of small dimensions which remained
      isolated over the centuries. METHODS: The MICROS study is a population-based
      survey on three small, isolated villages, characterized by: old settlement; small
      number of founders; high endogamy rates; slow/null population expansion. During
      the stage-1 (2002/03) genealogical data, screening questionnaires, clinical
      measurements, blood and urine samples, and DNA were collected for 1175 adult
      volunteers. Stage-2, concerning trait diagnoses, linkage analysis and association
      studies, is ongoing. The selection of the traits is being driven by expert
      clinicians. Preliminary, descriptive statistics were obtained. Power simulations
      for finding linkage on a quantitative trait locus (QTL) were undertaken. RESULTS:
      Starting from participants, genealogies were reconstructed for 50,037 subjects,
      going back to the early 1600s. Within the last five generations, subjects were
      clustered in one pedigree of 7049 subjects plus 178 smaller pedigrees (3 to 85
      subjects each). A significant probability of familial clustering was assessed for
      many traits, especially among the cardiovascular, neurological and respiratory
      traits. Simulations showed that the MICROS pedigree has a substantial power to
      detect a LOD score > or = 3 when the QTL specific heritability is > or = 20%.
      CONCLUSION: The MICROS study is an extensive, ongoing, two-stage survey aimed at
      characterizing the genetic epidemiology of Mendelian and complex diseases. Our
      approach, involving different scientific disciplines, is an advantageous strategy
      to define and to study population isolates. The isolation of the Alpine
      populations, together with the extensive data collected so far, make the MICROS
      study a powerful resource for the study of diseases in many fields of medicine.
      Recent successes and simulation studies give us confidence that our pedigrees can
      be valuable both in finding new candidates loci and to confirm existing candidate
      genes.

PMID- 17550582
TI  - Joint mapping of genes and conditions via multidimensional unfolding analysis.
AB  - BACKGROUND: Microarray compendia profile the expression of genes in a number of
      experimental conditions. Such data compendia are useful not only to group genes
      and conditions based on their similarity in overall expression over profiles but
      also to gain information on more subtle relations between genes and conditions.
      Getting a clear visual overview of all these patterns in a single easy-to-grasp
      representation is a useful preliminary analysis step: We propose to use for this
      purpose an advanced exploratory method, called multidimensional unfolding.
      RESULTS: We present a novel algorithm for multidimensional unfolding that
      overcomes both general problems and problems that are specific for the analysis
      of gene expression data sets. Applying the algorithm to two publicly available
      microarray compendia illustrates its power as a tool for exploratory data
      analysis: The unfolding analysis of a first data set resulted in a two
      dimensional representation which clearly reveals temporal regulation patterns for
      the genes and a meaningful structure for the time points, while the analysis of a
      second data set showed the algorithm's ability to go beyond a mere identification
      of those genes that discriminate between different patient or tissue types.
      CONCLUSION: Multidimensional unfolding offers a useful tool for preliminary
      explorations of microarray data: By relying on an easy-to-grasp low-dimensional
      geometric framework, relations among genes, among conditions and between genes
      and conditions are simultaneously represented in an accessible way which may
      reveal interesting patterns in the data. An additional advantage of the method is
      that it can be applied to the raw data without necessitating the choice of
      suitable genewise transformations of the data.

PMID- 17550583
TI  - Dietary n-3 fatty acids have suppressive effects on mucin upregulation in mice
      infected with Pseudomonas aeruginosa.
AB  - BACKGROUND: Mucin hypersecretion and mucus plugging in the airways are
      characteristic features of chronic respiratory diseases like cystic fibrosis (CF)
      and contribute to morbidity and mortality. In CF, Pseudomonas aeruginosa
      superinfections in the lung exacerbate inflammation and alter mucus properties.
      There is increasing evidence that n-3 polyunsaturated fatty acids (PUFAs) exhibit
      anti-inflammatory properties in many inflammatory diseases while n-6 PUFA
      arachidonic acid (AA) favors inflammatory mediators such as eicosanoids
      prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) that may enhance inflammatory
      reactions. This suggests that n-3 PUFAs may have a protective effect against
      mucus over-production in airway diseases. Therefore, we hypothesized that n-3
      PUFAs may downregulate mucins expression. METHODS: We designed an absolute real
      time PCR assay to assess the effect of a 5-week diet enriched either with n-3 or
      n-6 PUFAs on the expression of large mucins in the lungs of mice infected by P.
      aeruginosa. RESULTS: Dietary fatty acids did not influence mucin gene expression
      in healthy mice. Lung infection induced an increase of the secreted gel-forming
      mucin Muc5b and a decrease of the membrane bound mucin Muc4. These deregulations
      are modulated by dietary fatty acids with a suppressive effect of n-3 PUFAs on
      mucin (increase of Muc5b from 19-fold up to 3.6 x 10(5)-fold for the n-3 PUFAs
      treated group and the control groups, respectively, 4 days post-infection and
      decrease of Muc4 from 15-fold up to 3.2 x 10(4)-fold for the control and the n-3
      PUFAs treated groups, respectively, 4 days post-infection). CONCLUSION: Our data
      suggest that n-3 PUFAs enriched diet represents an inexpensive strategy to
      prevent or treat mucin overproduction in pulmonary bacterial colonization.

PMID- 17550584
TI  - Alterations of alveolar type II cells and intraalveolar surfactant after
      bronchoalveolar lavage and perfluorocarbon ventilation. An electron microscopical
      and stereological study in the rat lung.
AB  - BACKGROUND: Repeated bronchoalveolar lavage (BAL) has been used in animals to
      induce surfactant depletion and to study therapeutical interventions of
      subsequent respiratory insufficiency. Intratracheal administration of surface
      active agents such as perfluorocarbons (PFC) can prevent the alveolar collapse in
      surfactant depleted lungs. However, it is not known how BAL or subsequent PFC
      administration affect the intracellular and intraalveolar surfactant pool.
      METHODS: Male wistar rats were surfactant depleted by BAL and treated for 1 hour
      by conventional mechanical ventilation (Lavaged-Gas, n = 5) or partial liquid
      ventilation with PF 5080 (Lavaged-PF5080, n = 5). For control, 10 healthy animals
      with gas (Healthy-Gas, n = 5) or PF5080 filled lungs (Healthy-PF5080, n = 5) were
      studied. A design-based stereological approach was used for quantification of
      lung parenchyma and the intracellular and intraalveolar surfactant pool at the
      light and electron microscopic level. RESULTS: Compared to Healthy-lungs, Lavaged
      animals had more type II cells with lamellar bodies in the process of secretion
      and freshly secreted lamellar body-like surfactant forms in the alveoli. The
      fraction of alveolar epithelial surface area covered with surfactant and total
      intraalveolar surfactant content were significantly smaller in Lavaged-animals.
      Compared with Gas-filled lungs, both PF5080-groups had a significantly higher
      total lung volume, but no other differences. CONCLUSION: After BAL-induced
      alveolar surfactant depletion the amount of intracellularly stored surfactant is
      about half as high as in healthy animals. In lavaged animals short time liquid
      ventilation with PF5080 did not alter intra- or extracellular surfactant content
      or subtype composition.

PMID- 17550585
TI  - SELDI-TOF-MS ProteinChip array profiling of T-cell clones propagated in long-term
      culture identifies human profilin-1 as a potential bio-marker of
      immunosenescence.
AB  - BACKGROUND: The adaptive immune response requires waves of T-cell clonal
      expansion on contact with pathogen and elimination after clearance of the source
      of antigen. However, lifelong persistent infections with common viruses cause
      chronic antigenic stimulation which takes its toll on adaptive immunity in late
      life. Chronic antigenic stress results in deregulation of the T-cell response and
      accumulation of anergic cells. Longitudinal studies of the elderly show that this
      impacts on survival. Identifying the nature of the defects in chronically
      stimulated T-cells and protein bio-markers of these dysfunctional cells would
      help to understand age-associated compromised T-cell function (immunosenescence)
      and facilitate the development of targeted intervention strategies.The purpose of
      this work was to use surface-enhanced laser desorption/ionization time-of-flight
      mass spectrometry (SELDI-TOF-MS) to analyse proteins associated with T-cell
      senescence in order to identify potential bio-markers. Clonal populations of T
      cells isolated from elderly octogenarian and centenarian donors were grown in
      vitro until senescence, and early passage and late passage (pre-senescent) cells
      were analysed using SELDI-TOF-MS ProteinChip arrays. RESULTS: Discriminant
      analysis identified several protein or peptide peaks in the region of 14.5-16.5
      kDa that were associated with T-cell clone senescence. Human profilin-1, a
      ubiquitous protein associated with actin remodelling and cellular motility was
      unambiguously identified. Altered expression of profilin-1 in senescent T-cell
      clones was confirmed by Western blot analysis. CONCLUSION: Due to the proposed
      roles of profilin-1 in cellular survival, cytoskeleton remodelling, motility, and
      proliferation, it is hypothesised that differential expression of profilin-1 in
      ageing may contribute directly to immunosenescence.

PMID- 17550587
TI  - Association between celiac sprue and cryopyrin associated autoinflammatory
      disorders: a case report.
AB  - Cryopyrin-associated diseases may be characterized by rashes, fever, and
      sensorineural deafness, while celiac disease may present with symptoms of
      malabsorption and fatigue. Arthritis is seen in both conditions. We report a
      young child with histologically diagnosed celiac disease and a cryopyrinopathy.

PMID- 17550586
TI  - An insight into immunogenic salivary proteins of Anopheles gambiae in African
      children.
AB  - BACKGROUND: During blood feeding, the mosquito injects saliva into the vertebrate
      host. This saliva contains bioactive components which may play a role in pathogen
      transmission and in host-vector relationships by inducing an immune response in
      the vertebrate host. The evaluation of human immune responses to arthropod bites
      might also represent a research direction for assessing individual exposure to
      the bite of a malaria vector. METHODS: The present study examined the antibody
      (Ab) IgG response during the season of exposure to Anopheles gambiae bites in
      young children living in a malaria endemic area. Immunoblots were performed with
      An. gambiae saliva to detect anti-saliva Ab bands and the evolution of
      immunogenic bands at the peak of, and following, the transmission period.
      RESULTS: The results showed that anti-Anopheles Ab was directed against a limited
      number of salivary proteins (175, 115, 72 and 30 kDa bands). Specific IgG
      responses to mosquito salivary proteins were variable among exposed individuals;
      nevertheless, two major bands (175 and 72 kDa) were observed in all immune
      responder children. Analysis of the intensity of immunogenic bands revealed that
      IgG levels against the 175 kDa band were significantly higher during the peak
      period compared to the end period malaria transmission. CONCLUSION: This
      preliminary work supports the potential of using anti-saliva immune responses as
      a measure of exposure to Anopheles bites. The use of immunoblots coupled with
      evaluation of band intensity could be an adequate tool for distinguishing
      immunogenic salivary proteins as candidate markers of bite exposure. Furthermore,
      this study may open the way to design new epidemiological tools for evaluating
      the risk of malaria exposure.

PMID- 17550588
TI  - Neointimal hyperplasia persists at six months after sirolimus-eluting stent
      implantation in diabetic porcine.
AB  - BACKGROUND: Observational clinical studies have shown that patients with diabetes
      have less favorable results after percutaneous coronary intervention compared
      with the non-diabetic counterparts, but its mechanism remains unclear. The aim of
      this study was to examine the changes of neointimal hyperplasia after sirolimus
      eluting stent (SES) implantation in a diabetic porcine model, and to evaluate the
      impact of aortic inflammation on this proliferative process. METHODS: Diabetic
      porcine model was created with an intravenous administration of a single dose of
      streptozotocin in 15 Chinese Guizhou minipigs (diabetic group); each of them
      received 2 SES (Firebird, Microport Co, China) implanted into 2 separated major
      epicardial coronary arteries. Fifteen non-diabetic minipigs with SES implantation
      served as controls (control group). At 6 months, the degree of neointimal
      hyperplasia was determined by repeat coronary angiography, intravascular
      ultrasound (IVUS) and histological examination. Tumor necrosis factor (TNF)-alpha
      protein level in the aortic intima was evaluated by Western blotting, and TNF
      alpha, interleukin (IL)-1beta and IL-6 mRNA levels were assayed by reverse
      transcription and polymerase chain reaction. RESULTS: The distribution of stented
      vessels, diameter of reference vessels, and post-procedural minimal lumen
      diameter were comparable between the two groups. At 6-month follow-up, the degree
      of in-stent restenosis (40.4 +/- 24.0% vs. 20.2 +/- 17.7%, p < 0.05), late lumen
      loss (0.33 +/- 0.19 mm vs. 0.10 +/- 0.09 mm, p < 0.001) by quantitative
      angiography, percentage of intimal hyperplasia in the stented area (26.7 +/-
      19.2% vs. 7.3 +/- 6.1%, p < 0.001) by IVUS, and neointimal area (1.59 +/- 0.76
      mm2 vs. 0.41 +/- 0.18 mm2, p < 0.05) by histological examination were
      significantly exacerbated in the diabetic group than those in the controls.
      Significant increases in TNF-alpha protein and TNF-alpha, IL-1beta and IL-6 mRNA
      levels were observed in aortic intima in the diabetic group. CONCLUSION:
      Neointimal hyperplasia persisted at least up to 6 months after SES implantation
      in diabetic porcine, which may be partly related to an exaggerated inflammatory
      response within the blood vessel wall. Our results provide theoretical support
      for potential direct beneficial effects of anti-diabetic and anti-inflammation
      medications in reducing the risk of restenosis after stenting.

PMID- 17550589
TI  - Routine human papillomavirus genotyping by DNA sequencing in community hospital
      laboratories.
AB  - BACKGROUND: Human papillomavirus (HPV) genotyping is important for following up
      patients with persistent HPV infection and for evaluation of prevention strategy
      for the individual patients to be immunized with type-specific HPV vaccines. The
      aim of this study was to optimize a robust "low-temperature" (LoTemp) PCR system
      to streamline the research protocols for HPV DNA nested PCR-amplification
      followed by genotyping with direct DNA sequencing. The protocol optimization
      facilitates transferring this molecular technology into clinical laboratory
      practice. In particular, lowering the temperature by 10 degrees C at each step of
      thermocycling during in vitro DNA amplification yields more homogeneous PCR
      products. With this protocol, template purification before enzymatic cycle primer
      extensions is no longer necessary. RESULTS: The HPV genomic DNA extracted from
      liquid-based alcohol-preserved cervicovaginal cells was first amplified by the
      consensus MY09/MY11 primer pair followed by nested PCR with GP5+/GP6+ primers.
      The 150 bp nested PCR products were subjected to direct DNA sequencing. The
      hypervariable 34-50 bp DNA sequence downstream of the GP5+ primer site was
      compared to the known HPV DNA sequences stored in the GenBank using on-line BLAST
      for genotyping. The LoTemp ready-to-use PCR polymerase reagents proved to be
      stable at room temperature for at least 6 weeks. Nested PCR detected 107 isolates
      of HPV in 513 cervicovaginal clinical samples, all validated by DNA sequencing.
      HPV-16 was the most prevalent genotype constituting 29 of 107 positive cases
      (27.2%), followed by HPV-56 (8.5%). For comparison, Digene HC2 test detected
      62.6% of the 107 HPV isolates and returned 11 (37.9%) of the 29 HPV-16 positive
      cases as "positive for high-risk HPV". CONCLUSION: The LoTemp ready-to-use PCR
      polymerase system which allows thermocycling at 85 degrees C for denaturing, 40
      degrees C for annealing and 65 degrees C for primer extension can be adapted for
      target HPV DNA amplification by nested PCR and for preparation of clinical
      materials for genotyping by direct DNA sequencing. HPV genotyping is performed by
      on-line BLAST algorithm of a hypervariable L1 region. The DNA sequence is
      included in each report to the physician for comparison in following up patients
      with persistent HPV infection, a recognized tumor promoter in cancer induction.

PMID- 17550590
TI  - Inactivation of viruses by coherent excitations with a low power visible
      femtosecond laser.
AB  - BACKGROUND: Resonant microwave absorption has been proposed in the literature to
      excite the vibrational states of microorganisms in an attempt to destroy them.
      But it is extremely difficult to transfer microwave excitation energy to the
      vibrational energy of microorganisms due to severe absorption of water in this
      spectral range. We demonstrate for the first time that, by using a visible
      femtosecond laser, it is effective to inactivate viruses such as bacteriophage
      M13 through impulsive stimulated Raman scattering. RESULTS AND DISCUSSION: By
      using a very low power (as low as 0.5 nj/pulse) visible femtosecond laser having
      a wavelength of 425 nm and a pulse width of 100 fs, we show that M13 phages were
      inactivated when the laser power density was greater than or equal to 50 MW/cm2.
      The inactivation of M13 phages was determined by plaque counts and had been found
      to depend on the pulse width as well as power density of the excitation laser.
      CONCLUSION: Our experimental findings lay down the foundation for an innovative
      new strategy of using a very low power visible femtosecond laser to selectively
      inactivate viruses and other microorganisms while leaving sensitive materials
      unharmed by manipulating and controlling with the femtosecond laser system.

PMID- 17550591
TI  - Group A streptococcal septicaemia presenting as an acute abdomen in a child.
AB  - We present an unusual case of group A streptococcal septicaemia referred to a
      paediatric surgical unit as acute appendicitis and highlight the importance of
      remembering this condition as part of a differential diagnosis.

PMID- 17550592
TI  - Nucleated red blood cells in the blood of medical intensive care patients
      indicate increased mortality risk: a prospective cohort study.
AB  - INTRODUCTION: In critically ill patients, the appearance of nucleated red blood
      cells (NRBCs) in blood is associated with a variety of severe diseases.
      Generally, when NRBCs are detected in the patients' blood, the prognosis is poor.
      METHODS: In a prospective study, the detection of NRBCs was used for a daily
      monitoring of 383 medical intensive care patients. RESULTS: The incidence of
      NRBCs in medical intensive care patients was 17.5% (67/383). The mortality of
      NRBC-positive patients was 50.7% (34/67); this was significantly higher (p <
      0.001) than the mortality of NRBC-negative patients (9.8%, 31/316). Mortality
      increased with increasing NRBC concentration. Seventy-eight point six percent of
      the patients with NRBCs of more than 200/microl died. The detection of NRBCs is
      highly predictive of death, the odds ratio after adjustment for other laboratory
      and clinical prognostic indicators being 1.987 (p < 0.01) for each increase in
      the NRBC category (0/microl, 1 to 100/microl, 101 to 200/microl, and more than
      200/microl). Each step-up in the NRBC category increased the mortality risk as
      much as an increase in APACHE II (Acute Physiology and Chronic Health Evaluation
      II) score of approximately 4 points. The mortality of patients who were NRBC
      positive on the day of relocation from the intensive care unit to a peripheral
      ward was 27.6% (8/27). This was significantly higher than the mortality of
      patients who were NRBC-negative on the relocation day (8.6%, 28/325; p < 0.01).
      On average, NRBCs were detected for the first time 14 days (median, 3 days)
      before death. CONCLUSION: The routine analysis of NRBCs in blood is of high
      prognostic power with regard to mortality of critically ill patients. Therefore,
      this parameter may serve as a daily indicator of patients at high mortality risk.
      Furthermore, NRBC-positive intensive care patients should not be relocated to a
      normal ward but should obtain ongoing intensive care treatment.

PMID- 17550593
TI  - Progress on quality management in the German health system - a long and winding
      road.
AB  - The interest in quality management in health care has increased in the last
      decades as the financial crises in most health systems generated the need for
      solutions to contain costs while maintaining quality of care. In Germany the
      development of quality management procedures has been closely linked with health
      care reforms. Starting in the early nineties quality management issues gained
      momentum in reform legislation only 10 years later. This review summarizes recent
      developments in medical quality management as related to the federal reform
      legislation in Germany. It provides an overview on the infrastructure, actors and
      on the current discussion concerning quality management in medical care. Germany
      had to catch up on implementing quality management in the health system compared
      to other countries. Considerable progress has been made, however, it is
      recognized that the full integration of quality management will require long-term
      commitment in developing methods, instruments and communication procedures. The
      most ambitious project at present is the development of a comprehensive
      comparative quality management system for hospitals at national level, including
      public reporting. For the time being medical quality management in Germany is
      dealt with as a technical and professional issue while the aspects of patient
      orientation and transparency need further advancement.

PMID- 17550595
TI  - Selective cytotoxicity of pancratistatin-related natural Amaryllidaceae
      alkaloids: evaluation of the activity of two new compounds.
AB  - BACKGROUND: Pancratistatin (PST), a compound extracted from an Amaryllidaceae
      (AMD) family plant, has been shown to specifically induce apoptosis in cancer
      cells with no/minimal toxic effect on normal cells. A systematic synthetic
      approach has indicated that the minimum cytotoxic pharmacophore comprises the
      trans-fused b/c-ring system containing the 2, 3, 4-triol unit in the C-ring. To
      further explore the structure-activity relationship of this group of compounds we
      have investigated the anti-cancer efficacy and specificity of two PST-related
      natural compounds, AMD4 and AMD5. Both of these compounds lack the
      polyhydroxylated lycorane element of PST instead having a methoxy-substituted
      crinane skeleton. RESULTS: Our results indicate that AMD5 has efficacy and
      selectivity similar to PST, albeit at a 10-fold increased concentration.
      Interestingly AMD4 lacks apoptotic activity. CONCLUSION: Our results indicate
      that the phenanthridone skeleton in natural Amaryllidaceae alkaloids may be a
      significant common element for selectivity against cancer cells; furthermore, the
      configuration of the methoxy-side groups is responsible for higher binding
      affinity to the target protein/s thus making for a more efficient anti-cancer
      agent.

PMID- 17550594
TI  - Pain-related anxiety-like behavior requires CRF1 receptors in the amygdala.
AB  - Corticotropin-releasing factor receptor CRF1 has been implicated in the
      neurobiological mechanisms of anxiety and depression. The amygdala plays an
      important role in affective states and disorders such as anxiety and depression.
      The amygdala is also emerging as a neural substrate of pain affect. However, the
      involvement of the amygdala in the interaction of pain and anxiety remains to be
      determined. This study tested the hypothesis that CRF1 receptors in the amygdala
      are critically involved in pain-related anxiety. Anxiety-like behavior was
      determined in adult male rats using the elevated plus maze (EPM) test. The open
      arm preference (ratio of open arm entries to the total number of entries) was
      measured. Nocifensive behavior was assessed by measuring hindlimb withdrawal
      thresholds for noxious mechanical stimulation of the knee. Measurements were made
      in normal rats and in rats with arthritis induced in one knee by intraarticular
      injections of kaolin/carrageenan. A selective CRF1 receptor antagonist (NBI27914)
      or vehicle was administered systemically (i.p.) or into the central nucleus of
      the amygdala (CeA, by microdialysis). The arthritis group showed a decreased
      preference for the open arms in the EPM and decreased hindlimb withdrawal
      thresholds. Systemic or intraamygdalar (into the CeA) administration of NBI27914,
      but not vehicle, inhibited anxiety-like behavior and nocifensive pain responses,
      nearly reversing the arthritis pain-related changes. This study shows for the
      first time that CRF1 receptors in the amygdala contribute critically to pain
      related anxiety-like behavior and nocifensive responses in a model of arthritic
      pain. The results are a direct demonstration that the clinically well-documented
      relationship between pain and anxiety involves the amygdala.

PMID- 17550596
TI  - International CCN society and intercellular signaling.

PMID- 17550597
TI  - Exploring the role of organizational policies and procedures in promoting
      research utilization in registered nurses.
AB  - BACKGROUND: Policies and procedures (P&Ps) have been suggested as one possible
      strategy for moving research evidence into practice among nursing staff in
      hospitals. Research in the area of P&Ps is limited, however. This paper explores:
      1) nurses' use of eight specific research-based practices (RBPs) and RBP overall,
      2) nurses' use and understanding of P&Ps, and 3) the role of P&Ps in promoting
      research utilization. METHODS: Staff nurses from the eight health regions
      governing acute care services across the Canadian province of Newfoundland and
      Labrador completed an anonymous questionnaire regarding their use of eight RBPs
      and associated P&Ps. Data were also obtained from authorities in six of the eight
      regions about existing relevant P&Ps. We used descriptive statistics and
      multivariate regression analysis to assess the relationship between key
      independent variables and self-reported use of RBP. RESULTS: Use of the eight
      RBPs ranged from 7.8% to 88.6%, depending on the practice. Nurses ranked P&P
      manuals as their number one source of practice knowledge. Most respondents
      (84.8%) reported that the main reason they consult the P&P manual is to confirm
      they are practicing according to agency rules. Multivariate regression analysis
      identified three significant predictors of being a user versus non-user of RBP
      overall: awareness, awareness by regular use, and persuasion. Six significant
      predictors of being a consistent versus less consistent user of RBP overall were
      also identified: perception of P&P existence, unit, nursing experience, personal
      experience as a source of practice knowledge, number of existing research-based
      P&Ps, and lack of time as a barrier to consulting P&P manuals. CONCLUSION:
      Findings suggest that nurses use P&Ps to guide their practice. However, the mere
      existence of P&Ps is not sufficient to translate research into nursing practice.
      Individual and organizational factors related to nurses' understanding and use of
      P&Ps also play key roles. Thus, moving research evidence into practice will
      require careful interplay between the organization and the individual. P&Ps may
      be the interface through which this occurs.

PMID- 17550598
TI  - Azithromycin in the extremely low birth weight infant for the prevention of
      bronchopulmonary dysplasia: a pilot study.
AB  - BACKGROUND: Azithromycin reduces the severity of illness in patients with
      inflammatory lung disease such as cystic fibrosis and diffuse panbronchiolitis.
      Bronchopulmonary dysplasia (BPD) is a pulmonary disorder which causes significant
      morbidity and mortality in premature infants. BPD is pathologically characterized
      by inflammation, fibrosis and impaired alveolar development. The purpose of this
      study was to obtain pilot data on the effectiveness and safety of prophylactic
      azithromycin in reducing the incidence and severity of BPD in an extremely low
      birth weight (< or = 1000 grams) population. METHODS: Infants < or = 1000 g birth
      weight admitted to the University of Kentucky Neonatal Intensive Care Unit (level
      III, regional referral center) from 9/1/02-6/30/03 were eligible for this pilot
      study. The pilot study was double-blinded, randomized, and placebo-controlled.
      Infants were randomized to treatment or placebo within 12 hours of beginning
      mechanical ventilation (IMV) and within 72 hours of birth. The treatment group
      received azithromycin 10 mg/kg/day for 7 days followed by 5 mg/kg/day for the
      duration of the study. Azithromycin or placebo was continued until the infant no
      longer required IMV or supplemental oxygen, to a maximum of 6 weeks. Primary
      endpoints were incidence of BPD as defined by oxygen requirement at 36 weeks
      gestation, post-natal steroid use, days of IMV, and mortality. Data was analyzed
      by intention to treat using Chi-square and ANOVA. RESULTS: A total of 43
      extremely premature infants were enrolled in this pilot study. Mean gestational
      age and birth weight were similar between groups. Mortality, incidence of BPD,
      days of IMV, and other morbidities were not significantly different between
      groups. Post-natal steroid use was significantly less in the treatment group [31%
      (6/19)] vs. placebo group [62% (10/16)] (p = 0.05). Duration of mechanical
      ventilation was significantly less in treatment survivors, with a median of 13
      days (1-47 days) vs. 35 days (1-112 days)(p = 0.02). CONCLUSION: Our study
      suggests that azithromycin prophylaxis in extremely low birth weight infants may
      effectively reduce post-natal steroid use for infants. Further studies are needed
      to assess the effects of azithromycin on the incidence of BPD and possible less
      common side effects, before any recommendations regarding routine clinical use
      can be made.

PMID- 17550599
TI  - Large-scale analysis of transcriptional cis-regulatory modules reveals both
      common features and distinct subclasses.
AB  - BACKGROUND: Transcriptional cis-regulatory modules (for example, enhancers) play
      a critical role in regulating gene expression. While many individual regulatory
      elements have been characterized, they have never been analyzed as a class.
      RESULTS: We have performed the first such large-scale study of cis-regulatory
      modules in order to determine whether they have common properties that might aid
      in their identification and contribute to our understanding of the mechanisms by
      which they function. A total of 280 individual, experimentally verified cis
      regulatory modules from Drosophila were analyzed for a range of sequence-level
      and functional properties. We report here that regulatory modules do indeed share
      common properties, among them an elevated GC content, an increased level of
      interspecific sequence conservation, and a tendency to be transcribed into RNA.
      However, we find that dense clustering of transcription factor binding sites,
      especially homotypic clustering, which is commonly believed to be a general
      characteristic of regulatory modules, is rather a feature that belongs chiefly to
      a specific subclass. This has important implications for current computational
      approaches, many of which are biased toward this subset. We explore two new
      strategies to assess binding site clustering and gauge their performances with
      respect to their ability to detect all 280 modules and various functionally
      coherent subsets. CONCLUSION: Our findings demonstrate that cis-regulatory
      modules share common features that help to define them as a class and that may
      lead to new insights into mechanisms of gene regulation. However, these
      properties alone may not be sufficient to reliably distinguish regulatory from
      non-regulatory sequences. We also demonstrate that there are distinct subclasses
      of cis-regulatory modules that are more amenable to in silico detection than
      others and that these differences must be taken into account when attempting
      genome-wide regulatory element discovery.

PMID- 17550602
TI  - A bleeding kiss: intramural haematoma secondary to balloon angioplasty.
AB  - BACKGROUND: Intramural coronary haematoma following percutaneous coronary
      intervention in the absence of coronary dissection is a rare phenomenon. CASE
      PRESENTATION: A 69 year old lady with previous prosthetic aortic valve
      replacement underwent percutaneous coronary intervention (PCI) from the left
      mainstem to the left anterior descending artery (LAD) and kissing balloon
      inflations to the LAD and circumflex (Cx) arteries. Although intravascular
      ultrasound examination (IVUS) of both the LAD and Cx showed both vessels to be
      widely patent at the end of the procedure, she developed ischaemic chest pain six
      hours later. Repeat coronary angiography revealed a significant stenosis in the
      proximal Cx vessel, which was confirmed on IVUS to be intramural haematoma.
      CONCLUSION: In patients taking warfarin in addition to standard antiplatelet
      therapy, kissing balloon inflations should be carried out with caution.

PMID- 17550601
TI  - Dynamic resolution of functionally related gene sets in response to acute heat
      stress.
AB  - BACKGROUND: Using a gene clustering strategy we determined intracellular pathway
      relationships within skeletal myotubes in response to an acute heat stress
      stimuli. Following heat shock, the transcriptome was analyzed by microarray in a
      temporal fashion to characterize the dynamic relationship of signaling pathways.
      RESULTS: Bioinformatics analyses exposed coordination of functionally-related
      gene sets, depicting mechanism-based responses to heat shock. Protein turnover
      related pathways were significantly affected including protein folding, pre-mRNA
      processing, mRNA splicing, proteolysis and proteasome-related pathways. Many
      responses were transient, tending to normalize within 24 hours. CONCLUSION: In
      summary, we show that the transcriptional response to acute cell stress is
      largely transient and proteosome-centric.

PMID- 17550600
TI  - Comparison of Francisella tularensis genomes reveals evolutionary events
      associated with the emergence of human pathogenic strains.
AB  - BACKGROUND: Francisella tularensis subspecies tularensis and holarctica are
      pathogenic to humans, whereas the two other subspecies, novicida and
      mediasiatica, rarely cause disease. To uncover the factors that allow subspecies
      tularensis and holarctica to be pathogenic to humans, we compared their genome
      sequences with the genome sequence of Francisella tularensis subspecies novicida
      U112, which is nonpathogenic to humans. RESULTS: Comparison of the genomes of
      human pathogenic Francisella strains with the genome of U112 identifies genes
      specific to the human pathogenic strains and reveals pseudogenes that previously
      were unidentified. In addition, this analysis provides a coarse chronology of the
      evolutionary events that took place during the emergence of the human pathogenic
      strains. Genomic rearrangements at the level of insertion sequences (IS
      elements), point mutations, and small indels took place in the human pathogenic
      strains during and after differentiation from the nonpathogenic strain, resulting
      in gene inactivation. CONCLUSION: The chronology of events suggests a substantial
      role for genetic drift in the formation of pseudogenes in Francisella genomes.
      Mutations that occurred early in the evolution, however, might have been fixed in
      the population either because of evolutionary bottlenecks or because they were
      pathoadaptive (beneficial in the context of infection). Because the structure of
      Francisella genomes is similar to that of the genomes of other emerging or highly
      pathogenic bacteria, this evolutionary scenario may be shared by pathogens from
      other species.

PMID- 17550603
TI  - The ancestor of the Paulinella chromatophore obtained a carboxysomal operon by
      horizontal gene transfer from a Nitrococcus-like gamma-proteobacterium.
AB  - BACKGROUND: Paulinella chromatophora is a freshwater filose amoeba with
      photosynthetic endosymbionts (chromatophores) of cyanobacterial origin that are
      closely related to free-living Prochlorococcus and Synechococcus species (PS
      clade). Members of the PS-clade of cyanobacteria contain a proteobacterial form
      1A RubisCO (ribulose-1,5-bisphosphate carboxylase/oxygenase) that was acquired by
      horizontal gene transfer (HGT) of a carboxysomal operon. In rDNA-phylogenies, the
      Paulinella chromatophore diverged basal to the PS-clade, raising the question
      whether the HGT occurred before or after the split of the chromatophore ancestor.
      RESULTS: Phylogenetic analyses of the almost complete rDNA operon with an
      improved taxon sampling containing most known cyanobacterial lineages recovered
      the Paulinella chromatophore as sister to the complete PS-clade. The sequence of
      the complete carboxysomal operon of Paulinella was determined. Analysis of
      RubisCO large subunit (rbcL) sequences revealed that Paulinella shares the
      proteobacterial form 1A RubisCO with the PS-clade. The gamma-proteobacterium
      Nitrococcus mobilis was identified as sister of the Paulinella chromatophore and
      the PS-clade in the RubisCO phylogeny. Gene content and order in the carboxysomal
      operon correlates well with the RubisCO phylogeny demonstrating that the complete
      carboxysomal operon was acquired by the common ancestor of the Paulinella
      chromatophore and the PS-clade through HGT. The carboxysomal operon shows a
      significantly elevated AT content in Paulinella, which in the rbcL gene is
      confined to third codon positions. Combined phylogenies using rbcL and the rDNA
      operon resulted in a nearly fully resolved tree of the PS-clade. CONCLUSION: The
      HGT of the carboxysomal operon predated the divergence of the chromatophore
      ancestor from the PS-clade. Following HGT and divergence of the chromatophore
      ancestor, diversification of the PS-clade into at least three subclades occurred.
      The gamma-proteobacterium Nitrococcus mobilis represents the closest known
      relative to the donor of the carboxysomal operon. The isolated position of the
      Paulinella chromatophore in molecular phylogenies as well as its elevated AT
      content suggests that the Paulinella chromatophore has already undergone typical
      steps in the reductive evolution of an endosymbiont.

PMID- 17550604
TI  - Role of inhibin and activin in the modulation of gonadotropin- and steroid
      induced oocyte maturation in the teleost Fundulus heteroclitus.
AB  - BACKGROUND: Activin and inhibin are glycoproteins structurally related to the
      transforming growth factor-beta superfamily. These peptides were first described
      as factors that regulate the follicle-stimulating hormone (FSH) at the pituitary
      level. The possible role of inhibin and activin, at the ovarian level, in
      mediating the stimulatory actions of a Fundulus pituitary extract (FPE) and
      17alpha,20beta-dihydroprogesterone (DHP) on oocyte maturation was investigated in
      this study. METHODS: In vitro culture of ovarian follicles and induction of
      oocyte maturation were carried out in 75% Leibovitz L-15 medium. Follicles or
      denuded oocytes were exposed to FPE, inhibin, activin, ethanol vehicle (control
      group), or DHP. The competence of the follicles or denuded oocytes to respond to
      the hormones was assessed by scoring germinal vesicle breakdown (GVBD) used as an
      indication of the reinitiation of meiosis or oocyte maturation. DHP level was
      measured by radioimmunoassay. RESULTS: Addition of FPE promoted the synthesis of
      DHP by the granulose cells of fully grown ovarian follicles and thus stimulated
      GVBD in the oocyte. Presence of porcine inhibin did not hinder the synthesis of
      DHP stimulated by FPE, although it did inhibit the subsequent GVBD in a dose
      dependent manner, suggesting that the action of inhibin was at the oocyte level.
      Similarly to the findings with FPE, inhibin also blocked the DHP-induced GVBD in
      intact follicles, as well as the spontaneous and steroid-induced GVBD of denuded
      oocyte. Inhibin straightforwardly blocked the response to a low dose of DHP
      throughout the culture period, while higher doses of the steroid appeared to
      overcome the inhibitory effect especially at later times. In contrast to inhibin,
      recombinant human activin A significantly enhanced DHP-induced GVBD in a dose
      dependent manner after 48 hr, although activin alone was not able to induce GVBD
      without the presence of the steroid. CONCLUSION: Taking together with our
      previous studies that demonstrate the presence of activin/inhibin subunits in the
      ovary of F. heteroclitus, these in vitro findings indicate that inhibin and
      activin are local regulators in the teleost ovary and have opposing effects in
      modulating oocyte maturation.

PMID- 17550605
TI  - The antinociceptive effect of systemic gabapentin is related to the type of
      sensitization-induced hyperalgesia.
AB  - BACKGROUND: Gabapentin is a structural analogue of gamma-aminobutyric acid with
      strong anticonvulsant and analgesic activities. Important discrepancies are
      observed on the effectiveness and potency of gabapentin in acute nociception and
      sensitization due to inflammation and neuropathy. There is also some controversy
      in the literature on whether gabapentin is only active in central areas of the
      nervous system or is also effective in the periphery. This is probably due to the
      use of different experimental models, routes of administration and types of
      sensitization. The aim of the present study was to investigate the influence of
      the spinal cord sensitization on the antinociceptive activity of gabapentin in
      the absence and in the presence of monoarthritis and neuropathy, using the same
      experimental protocol of stimulation and the same technique of evaluation of
      antinociception. METHODS: We studied the antinociceptive effects of iv.
      gabapentin in spinal cord neuronal responses from adult male Wistar rats using
      the recording of single motor units technique. Gabapentin was studied in the
      absence and in the presence of sensitization due to arthritis and neuropathy,
      combining noxious mechanical and repetitive electrical stimulation (wind-up).
      RESULTS: The experiments showed that gabapentin was effective in arthritic (max.
      effect of 41 +/- 15% of control and ID50 of 1,145 +/- 14 micromol/kg; 200 mg/kg)
      and neuropathic rats (max. effect of 20 +/- 8% of control and ID50 of 414 +/- 27
      micromol/kg; 73 mg/kg) but not in normal rats. The phenomenon of wind-up was dose
      dependently reduced by gabapentin in neuropathy but not in normal and arthritic
      rats. CONCLUSION: We conclude that systemic gabapentin is a potent and effective
      antinociceptive agent in sensitization caused by arthritis and neuropathy but not
      in the absence of sensitization. The potency of the antinociception was directly
      related to the intensity of sensitization in the present experimental conditions.
      The effect is mainly located in central areas in neuropathy since wind-up was
      significantly reduced, however, an action on inflammation-induced sensitized
      nociceptors is also likely.

PMID- 17550606
TI  - Lentiviral vector design using alternative RNA export elements.
AB  - BACKGROUND: Lentiviral vectors have been designed with complex RNA export
      sequences in both the integrating and packaging plasmids in order to co-ordinate
      efficient vector production. Recent studies have attempted to replace the
      existing complex rev/RRE system with a more simplistic RNA export system from
      simple retroviruses to make these vectors in a rev-independent manner. RESULTS:
      Towards this end, lentiviral transfer plasmids were modified with various cis
      acting DNA elements that co-ordinate RNA export during viral production to
      determine their ability to affect the efficiency of vector titer and transduction
      in different immortalized cell lines in vitro. It was found that multiple copies
      of the constitutive transport element (CTE) originating from different simian
      retroviruses, including simian retrovirus type 1 (SRV-1) and type-2 (SRV-2) and
      Mason-Pfizer (MPV) could be used to eliminate the requirement for the rev
      responsive element (RRE) in the transfer and packaging plasmids with titers >106
      T.U./mL (n = 4-8 preparations). The addition of multiple copies of the murine
      intracisternal type A particle, the woodchuck post-regulatory element (WPRE), or
      single and dual copies of the simian CTE had minimal effect on viral titer.
      Immortalized cell lines from different species were found to be readily
      transduced by VSV-G pseudotyped lentiviral vectors containing the multiple copies
      of the CTE similar to the findings in HeLa cells, although the simian-derived CTE
      were found to have a lower infectivity into murine cell lines compared to the
      other species. CONCLUSION: These studies demonstrated that the rev-responsive
      element (RRE) could be replaced with other constitutive transport elements to
      produce equivalent titers using lentivectors containing the RRE sequence in
      vitro, but that concatemerization of the CTE or the close proximity of RNA export
      sequences was needed to enhance vector production.

PMID- 17550607
TI  - The focal adhesion protein Hic-5 is highly expressed in the rat myometrium during
      late pregnancy and labour and co-localizes with FAK.
AB  - BACKGROUND: Myometrial growth and remodeling of the cytoskeleton and focal
      adhesions during late pregnancy may be critical aspects of myometrial activation
      and thus labour. Yet our understanding of these aspects is inhibited by the
      paucity of information concerning the components of focal adhesions in the
      myometrium. The focal adhesion protein hydrogen peroxide-inducible clone-5 (Hic
      5) has recently been found in mononuclear smooth muscle but was not examined in
      the myometrium during pregnancy. Thus, the goal of this study was to characterize
      Hic-5 mRNA and protein expression in the rat myometrium during pregnancy and
      labour. METHODS: Rat myometrium samples were obtained from non-pregnant animals,
      pregnant animals on days (d) 6, 12, 15, 17, 19, 21, 22, 23 (active labour) and 1
      day postpartum (PP). In addition, myometrium samples were collected from rats
      within a progesterone-delayed labour paradigm. Hic-5 mRNA expression was analyzed
      by Northern blot analysis while Hic-5 protein expression was examined by
      immunoblot and immunofluorescence analysis. RESULTS: Hic-5 mRNA expression on
      d15, d19 and d21 was found to be significantly elevated compared to d6 and d12 of
      pregnancy and expression on d23 was significantly elevated over d6 (p < 0.05).
      Immunofluorescence analysis demonstrated that detection of Hic-5 protein in the
      circular muscle layer appeared to increase from d17 onwards, except PP, and Hic-5
      was detectable in the cell cytoplasm and more continuously associated with
      myometrial cell membranes. In the longitudinal muscle layer Hic-5 was readily
      detectable by d15 and thereafter and primarily associated at myometrial cell
      membranes. Co-immunofluorescence analysis of potential Hic-5 and focal adhesion
      kinase (FAK) association in situ demonstrated a limited level of co-localization
      on d19, d23 and PP in the circular muscle layer while in the longitudinal muscle
      layer Hic-5 and FAK were readily co-localized at myometrial cell membranes.
      CONCLUSION: Hic-5 is highly expressed in the rat myometrium during late pregnancy
      and labour and co-localizes with FAK in situ. Our results are consistent with a
      potential role for Hic-5 in focal adhesion remodeling in the rat myometrium
      during late pregnancy.

PMID- 17550609
TI  - Method for evaluating prediction models that apply the results of randomized
      trials to individual patients.
AB  - INTRODUCTION: The clinical significance of a treatment effect demonstrated in a
      randomized trial is typically assessed by reference to differences in event rates
      at the group level. An alternative is to make individualized predictions for each
      patient based on a prediction model. This approach is growing in popularity,
      particularly for cancer. Despite its intuitive advantages, it remains plausible
      that some prediction models may do more harm than good. Here we present a novel
      method for determining whether predictions from a model should be used to apply
      the results of a randomized trial to individual patients, as opposed to using
      group level results. METHODS: We propose applying the prediction model to a data
      set from a randomized trial and examining the results of patients for whom the
      treatment arm recommended by a prediction model is congruent with allocation.
      These results are compared with the strategy of treating all patients through use
      of a net benefit function that incorporates both the number of patients treated
      and the outcome. We examined models developed using data sets regarding adjuvant
      chemotherapy for colorectal cancer and Dutasteride for benign prostatic
      hypertrophy. RESULTS: For adjuvant chemotherapy, we found that patients who would
      opt for chemotherapy even for small risk reductions, and, conversely, those who
      would require a very large risk reduction, would on average be harmed by using a
      prediction model; those with intermediate preferences would on average benefit by
      allowing such information to help their decision making. Use of prediction could,
      at worst, lead to the equivalent of an additional death or recurrence per 143
      patients; at best it could lead to the equivalent of a reduction in the number of
      treatments of 25% without an increase in event rates. In the Dutasteride case,
      where the average benefit of treatment is more modest, there is a small benefit
      of prediction modelling, equivalent to a reduction of one event for every 100
      patients given an individualized prediction. CONCLUSION: The size of the benefit
      associated with appropriate clinical implementation of a good prediction model is
      sufficient to warrant development of further models. However, care is advised in
      the implementation of prediction modelling, especially for patients who would opt
      for treatment even if it was of relatively little benefit.

PMID- 17550610
TI  - Characterization and modeling of the Haemophilus influenzae core and supragenomes
      based on the complete genomic sequences of Rd and 12 clinical nontypeable
      strains.
AB  - BACKGROUND: The distributed genome hypothesis (DGH) posits that chronic bacterial
      pathogens utilize polyclonal infection and reassortment of genic characters to
      ensure persistence in the face of adaptive host defenses. Studies based on random
      sequencing of multiple strain libraries suggested that free-living bacterial
      species possess a supragenome that is much larger than the genome of any single
      bacterium. RESULTS: We derived high depth genomic coverage of nine nontypeable
      Haemophilus influenzae (NTHi) clinical isolates, bringing to 13 the number of
      sequenced NTHi genomes. Clustering identified 2,786 genes, of which 1,461 were
      common to all strains, with each of the remaining 1,328 found in a subset of
      strains; the number of clusters ranged from 1,686 to 1,878 per strain. Genic
      differences of between 96 and 585 were identified per strain pair. Comparisons of
      each of the NTHi strains with the Rd strain revealed between 107 and 158
      insertions and 100 and 213 deletions per genome. The mean insertion and deletion
      sizes were 1,356 and 1,020 base-pairs, respectively, with mean maximum insertions
      and deletions of 26,977 and 37,299 base-pairs. This relatively large number of
      small rearrangements among strains is in keeping with what is known about the
      transformation mechanisms in this naturally competent pathogen. CONCLUSION: A
      finite supragenome model was developed to explain the distribution of genes among
      strains. The model predicts that the NTHi supragenome contains between 4,425 and
      6,052 genes with most uncertainty regarding the number of rare genes, those that
      have a frequency of <0.1 among strains; collectively, these results support the
      DGH.

PMID- 17550611
TI  - Cognitive remediation therapy for patients with anorexia nervosa: preliminary
      findings.
AB  - BACKGROUND: Anorexia nervosa (AN) is a severe mental illness. Drug treatments are
      not effective and there is no established first choice psychological treatment
      for adults with AN. Neuropsychological studies have shown that patients with AN
      have difficulties in cognitive flexibility: these laboratory based findings have
      been used to develop a clinical intervention based on Cognitive Remediation
      Therapy (CRT) which aims to use cognitive exercises to strengthen thinking
      skills. AIMS: 1) To conduct a preliminary investigation of CRT in patients with
      AN 2) to explore whether cognitive training improves performance in set shifting
      tasks 3) to explore whether CRT exercises are appropriate and acceptable to AN
      patients 4) to use the data to improve a CRT module for AN patients. METHODS:
      Intervention was comprised of ten 45 minute sessions of CRT. Four patients with
      AN were assessed before and after the ten sessions using five set shifting tests
      and clinical assessments. At the end, each patient wrote a letter providing
      feedback on the intervention. RESULTS: Post intervention, three of the five set
      shifting assessments showed a moderate to large effect size in performance and
      two showed a large effect size in performance, both indicative of improved
      flexibility. Patients were aware of an improvement in their cognitive flexibility
      qualitative feedback was generally positive towards CRT. DISCUSSION: This
      preliminary study suggests that CRT changed performance on flexibility tasks and
      may be beneficial for acute, treatment resistant patients with AN. Feedback
      gathered from this small case series has enabled modification of the intervention
      for a future larger study, for example, by linking exercises with real life
      behavioural tasks and including exercises that encourage global thinking.
      CONCLUSION: This exploratory study has produced encouraging data supporting the
      use of CRT in patients with AN: it has also provided insight into how the module
      should be tailored to maximise its effectiveness for people with acute AN.

PMID- 17550612
TI  - hZip2 and hZip3 zinc transporters are down regulated in human prostate
      adenocarcinomatous glands.
AB  - BACKGROUND: The normal human prostate glandular epithelium has the unique
      function of accumulating high levels of zinc. In prostate cancer this capability
      is lost as an early event in the development of the malignant cells. The
      mechanism and factors responsible for the ability of the normal epithelial cells
      to accumulate zinc and the loss of this capability in the malignant cells need to
      be identified. We previously reported that Zip1 is an important zinc uptake
      transporter in prostate cells and is down regulated in the malignant cells in
      situ along with the depletion of zinc levels. In this report we investigated the
      expression of two other Zip family zinc transporters, Zip2 and Zip3 in malignant
      versus nonmalignant (normal and BPH) glands. Zip2 and Zip3 relative protein
      levels were determined by immunohistochemistry analysis of human prostate tissue
      sections. RESULTS: Normal and BPH glandular epithelium consistently exhibited the
      strong presence of both Zip 2 and Zip3; whereas both transporters consistently
      were essentially non-detectable in the malignant glands. This represents the
      first report of the expression of Zip3 in human prostate tissue; and more
      importantly, reveals that ZiP2 and Zip3 are down regulated in malignant cells in
      situ as we also had demonstrated for Zip1. Zip2 and Zip3 transporter proteins
      were localized predominantly at the apical cell membrane, which is in contrast to
      the Zip1 localization at the basolateral membrane. Zip2 and Zip3 seemingly are
      associated with the re-uptake of zinc from prostatic fluid. CONCLUSION: These
      results coupled with previous reports implicate Zip2 and Zip3 along with Zip1 as
      important zinc uptake transporters involved in the unique ability of prostate
      cells to accumulate high cellular zinc levels. Zip1 is important for the
      extraction of zinc from circulation as the primary source of cellular zinc. Zip 2
      and Zip3 appear to be important for retention of the zinc in the cellular
      compartment. The down regulation of all three transporters in the malignant cells
      is consistent with the loss of zinc accumulation in these cells. Since zinc
      imposes tumor suppressor effects, the silencing of the gene expression for these
      transporters is a required event for the manifestation of the malignant
      activities of the neoplastic cells. This now provides new insights into the
      genetic/molecular events associated with the development of prostate cancer; and
      supports our concept of Zip1, and now Zip2 and Zip3, as tumor suppressor genes
      and zinc as a tumor suppressor agent.

PMID- 17550613
TI  - Expression of RNA virus proteins by RNA polymerase II dependent expression
      plasmids is hindered at multiple steps.
AB  - BACKGROUND: Proteins of human and animal viruses are frequently expressed from
      RNA polymerase II dependent expression cassettes to study protein function and to
      develop gene-based vaccines. Initial attempts to express the G protein of
      vesicular stomatitis virus (VSV) and the F protein of respiratory syncytial virus
      (RSV) by eukaryotic promoters revealed restrictions at several steps of gene
      expression. RESULTS: Insertion of an intron flanked by exonic sequences 5'
      terminal to the open reading frames (ORF) of VSV-G and RSV-F led to detectable
      cytoplasmic mRNA levels of both genes. While the exonic sequences were sufficient
      to stabilise the VSV-G mRNA, cytoplasmic mRNA levels of RSV-F were dependent on
      the presence of a functional intron. Cytoplasmic VSV-G mRNA levels led to readily
      detectable levels of VSV-G protein, whereas RSV-F protein expression remained
      undetectable. However, RSV-F expression was observed after mutating two of four
      consensus sites for polyadenylation present in the RSV-F ORF. Expression levels
      could be further enhanced by codon optimisation. CONCLUSION: Insufficient
      cytoplasmic mRNA levels and premature polyadenylation prevent expression of RSV-F
      by RNA polymerase II dependent expression plasmids. Since RSV replicates in the
      cytoplasm, the presence of premature polyadenylation sites and elements leading
      to nuclear instability should not interfere with RSV-F expression during virus
      replication. The molecular mechanisms responsible for the destabilisation of the
      RSV-F and VSV-G mRNAs and the different requirements for their rescue by
      insertion of an intron remain to be defined.

PMID- 17550614
TI  - Spatial and temporal proximity as factors in shape recognition.
AB  - Prior research from this laboratory examined minimal stimulus conditions that
      allow for recognition of objects. Using briefly flashed dots that marked the
      outer border of objects, it was found that timing differentials within and among
      successive dot pairs affected recognition, with significant declines being seen
      by the addition of temporal separations in the millisecond range. These
      experiments were done with dot pairs that had close spatial proximity, which
      leaves open the possibility that the effects could be attributed to strictly
      local neural encoding processes. The present research reports that spatial
      separation of pair members resulted in declines in recognition that were similar
      to those produced with close spacing of pair members. Both for close and
      separated dot pairs, recognition was best when they were displayed with near
      simultaneity, which likely generated synchronized spikes in the retina. These
      results provide cognitive evidence in support of proposals that synchronous
      neural activity is part of the image encoding process. The physiological
      literature is surveyed and discussed in an effort to delineate the issues, and a
      tentative model of retinal response to these stimulus conditions is offered.

PMID- 17550615
TI  - Non-invasive assessment of coronary artery bypass graft patency using 16-slice
      computed tomography angiography.
AB  - BACKGROUND: Invasive coronary angiography is the gold standard means of imaging
      bypass vessels and carries a small but potentially serious risk of local vascular
      complications, including myocardial infarction, stroke and death. We evaluated
      computed tomography as a non-invasive means of assessing graft patency. METHODS:
      Fifty patients with previous coronary artery bypass surgery who were listed for
      diagnostic coronary angiography underwent contrast enhanced computed tomography
      angiography using a 16-slice computed tomography scanner. Images were
      retrospectively gated to the electrocardiogram and two dimensional axial,
      multiplanar and three dimensional reconstructions acquired. Sensitivity,
      specificity, positive and negative predictive value, accuracy and level of
      agreement for detection of graft patency by multidetector computed tomography.
      RESULTS: A total of 116 grafts were suitable for analysis. The specificity of CT
      for the detection of graft patency was 100%, with a sensitivity of 92.8%,
      positive predictive value 100%, negative predictive value 85.8% and an accuracy
      of 94.8%. The kappa value of agreement between the two means of measuring graft
      patency was 0.9. Mean radiation dose was 9.0 +/- 7.2 mSv for coronary angiography
      and 18.5 +/- 4 mSv for computed tomography. Pooled analysis of eight studies,
      incorporating 932 grafts, confirmed a 97% accuracy for the detection of graft
      patency by multidetector computed tomography. CONCLUSION: Computed tomography is
      an accurate, rapid and non-invasive method of assessing coronary artery bypass
      graft patency. However, this was achieved at the expense of an increase in
      radiation dose.

PMID- 17550616
TI  - Production of surfactin from Bacillus subtilis MZ-7 grown on pharmamedia
      commercial medium.
AB  - BACKGROUND: Commercial medium (Pharmamedia) was investigated for the production
      of surfactin by Bacillus subtilis MZ-7. Different media (defined, semi-defined,
      and complex media) were compared for the production of surfactin after fixing the
      least influential variables in standardized fermentation conditions. Carbohydrate
      and nitrogen supplements were also tried to improve production in Pharmamedia.
      RESULTS: Surfactin production was confirmed using PCR along with other analytical
      techniques and monitored by RP-HPLC and MALDI-TOF-MS. We found that optimized and
      brain heart infusion media were best for production of surfactin (280 mg/L) and a
      relatively comparable production with Pharmamedia (220 mg/L), however,
      supplementing Pharmamedia with Fe+ (4.0 mM) and sucrose (2 g/L) leads to a
      maximum production of about (300 mg/L). CONCLUSION: Cottonseed-derived medium
      proved to be a suitable substrate for the production of bioactive substances
      including surfactin, a useful compound in both medical and biotechnological
      fields. The medium provided not only higher product accumulations but at
      considerably lower cost with potential for large scale industrial applications.

PMID- 17550617
TI  - Strong inverse association between physical fitness and overweight in
      adolescents: a large school-based survey.
AB  - BACKGROUND: Studies examining the relationship between physical fitness and
      obesity in children have had mixed results despite their interrelationship making
      intuitive sense. We examined the relationship between physical fitness and
      overweight and obesity in a large sample of adolescents in the Republic of
      Seychelles (Indian Ocean, African region). METHODS: All students of four grades
      of all secondary schools performed nine physical fitness tests. These tests
      assessed agility, strength and endurance, and included the multistage shuttle
      run, a validated measure of maximal oxygen uptake. Weight and height were
      measured, body mass index (BMI) calculated, and "overweight" and "obesity" were
      defined based on the criteria of the International Obesity Task Force. We defined
      "lean" weight as age- and sex-specific BMI <10th percentile. Age- and sex
      specific percentiles for each fitness test were calculated. "Good" performance
      was defined as a result >or=75th percentile. RESULTS: Data were available in 2203
      boys and 2143 girls from a total of 4599 eligible students aged 12-15 years. The
      prevalence of overweight (including obesity) was 11.2% (95% confidence interval:
      9.9-12.4) in boys and 17.5% (15.9-19.1) in girls. For 7 of the 9 tests, the
      relationship between BMI and fitness score, as assessed by locally weighted
      regression, was characterized by a marked inverse J shape. Students with normal
      body weight achieved "good" performance markedly more often than overweight or
      obese students on 7 of the 9 tests of fitness and more often than lean children.
      For example, good performance for the multistage shuttle run was achieved by
      25.6% (SE: 2.1) of lean students, 29.6% (0.8) of normal weight students, 7.9%
      (1.3) of overweight students and 1.2% (0.9) of obese students. CONCLUSION: This
      cross-sectional study shows a strong inverse relationship between fitness and
      excess body weight in adolescents. Improving fitness in adolescents, likely
      through increasing physical activity, might need special interventions that are
      responsive to the ability and needs of overweight children.

PMID- 17550618
TI  - Dynamic morphometric characterization of local connective tissue network
      structure in humans using ultrasound.
AB  - BACKGROUND: In humans, connective tissue forms a complex, interconnected network
      throughout the body that may have mechanosensory, regulatory and signaling
      functions. Understanding these potentially important phenomena requires non
      invasive measurements of collagen network structure that can be performed in live
      animals or humans. The goal of this study was to show that ultrasound can be used
      to quantify dynamic changes in local connective tissue structure in vivo. We
      first performed combined ultrasound and histology examinations of the same tissue
      in two subjects undergoing surgery: in one subject, we examined the relationship
      of ultrasound to histological images in three dimensions; in the other, we
      examined the effect of a localized tissue perturbation using a previously
      developed robotic acupuncture needling technique. In ten additional non-surgical
      subjects, we quantified changes in tissue spatial organization over time during
      needle rotation vs. no rotation using ultrasound and semi-variogram analyses.
      RESULTS: 3-D renditions of ultrasound images showed longitudinal echogenic sheets
      that matched with collagenous sheets seen in histological preparations. Rank
      correlations between serial 2-D ultrasound and corresponding histology images
      resulted in high positive correlations for semi-variogram ranges computed
      parallel (r = 0.79, p < 0.001) and perpendicular (r = 0.63, p < 0.001) to the
      surface of the skin, indicating concordance in spatial structure between the two
      data sets. Needle rotation caused tissue displacement in the area surrounding the
      needle that was mapped spatially with ultrasound elastography and corresponded to
      collagen bundles winding around the needle on histological sections. In semi
      variograms computed for each ultrasound frame, there was a greater change in the
      area under the semi-variogram curve across successive frames during needle
      rotation compared with no rotation. The direction of this change was
      heterogeneous across subjects. The frame-to-frame variability was 10-fold (p <
      0.001) greater with rotation than with no rotation indicating changes in tissue
      structure during rotation. CONCLUSION: The combination of ultrasound and semi
      variogram analyses allows quantitative assessment of dynamic changes in the
      structure of human connective tissue in vivo.

PMID- 17550619
TI  - Exacerbation of acidosis during ischemia and reperfusion arrhythmia in hearts
      from type 2 Diabetic Otsuka Long-Evans Tokushima Fatty rats.
AB  - BACKGROUND: Sensitivity to ischemia and its underlying mechanisms in type 2
      diabetic hearts are still largely unknown. Especially, correlation between
      reperfusion induced ventricular arrhythmia and changes in intracellular pH has
      not been elucidated. METHODS AND RESULTS: Male Otsuka Long-Evans Tokushima Fatty
      (OLETF) rats at 16 and 32 weeks of age were used along with age-matched
      nondiabetic Long-Evans Tokushima Otsuka (LETO) rats. Hearts from rats in these 4
      groups were perfused in the working heart mode, thus inducing whole heart
      ischemia. At 16 weeks of age, no differences in blood glucose levels or incidence
      and duration of reperfusion arrhythmia were found between the strains. At 32
      weeks of age, both impaired glucose tolerance and obesity were observed in the
      OLETF rats. Further, the duration of reperfusion-induced ventricular fibrillation
      (VF) was significantly longer in the OLETF rats, while the pH level was
      significantly lower and proton contents were significantly higher in coronary
      effluent during ischemia in those rats. Following treatment with troglitazone,
      improvements in pH and proton level in coronary effluent during ischemia were
      observed, as was the duration of reperfusion-induced VF in OLETF rats at 32 weeks
      of age. CONCLUSION: The hearts of spontaneously diabetic OLETF rats were found to
      be more susceptible to ischemic insult. Troglitazone treatment improved ischemic
      tolerance by improving glucose metabolism in the myocardium of those rats.

PMID- 17550620
TI  - Remote and field level quantification of vegetation covariates for malaria
      mapping in three rice agro-village complexes in Central Kenya.
AB  - BACKGROUND: We examined algorithms for malaria mapping using the impact of
      reflectance calibration uncertainties on the accuracies of three vegetation
      indices (VI)'s derived from QuickBird data in three rice agro-village complexes
      Mwea, Kenya. We also generated inferential statistics from field sampled
      vegetation covariates for identifying riceland Anopheles arabiensis during the
      crop season. All aquatic habitats in the study sites were stratified based on
      levels of rice stages; flooded, land preparation, post-transplanting, tillering,
      flowering/maturation and post-harvest/fallow. A set of uncertainty propagation
      equations were designed to model the propagation of calibration uncertainties
      using the red channel (band 3: 0.63 to 0.69 microm) and the near infra-red (NIR)
      channel (band 4: 0.76 to 0.90 microm) to generate the Normalized Difference
      Vegetation Index (NDVI) and the Soil Adjusted Vegetation Index (SAVI). The
      Atmospheric Resistant Vegetation Index (ARVI) was also evaluated incorporating
      the QuickBird blue band (Band 1: 0.45 to 0.52 microm) to normalize atmospheric
      effects. In order to determine local clustering of riceland habitats Gi*(d)
      statistics were generated from the ground-based and remotely-sensed ecological
      databases. Additionally, all riceland habitats were visually examined using the
      spectral reflectance of vegetation land cover for identification of highly
      productive riceland Anopheles oviposition sites. RESULTS: The resultant VI
      uncertainties did not vary from surface reflectance or atmospheric conditions.
      Logistic regression analyses of all field sampled covariates revealed emergent
      vegetation was negatively associated with mosquito larvae at the three study
      sites. In addition, floating vegetation (-ve) was significantly associated with
      immature mosquitoes in Rurumi and Kiuria (-ve); while, turbidity was also
      important in Kiuria. All spatial models exhibit positive autocorrelation; similar
      numbers of log-counts tend to cluster in geographic space. The spectral
      reflectance from riceland habitats, examined using the remote and field
      stratification, revealed post-transplanting and tillering rice stages were most
      frequently associated with high larval abundance and distribution. CONCLUSION:
      NDVI, SAVI and ARVI generated from QuickBird data and field sampled vegetation
      covariates modeled cannot identify highly productive riceland An. arabiensis
      aquatic habitats. However, combining spectral reflectance of riceland habitats
      from QuickBird and field sampled data can develop and implement an Integrated
      Vector Management (IVM) program based on larval productivity.

PMID- 17550621
TI  - Extracorporeal membrane oxygenator as a bridge to successful surgical repair of
      bronchopleural fistula following bilateral sequential lung transplantation: a
      case report and review of literature.
AB  - BACKGROUND: Lung transplantation (LTx) is widely accepted as a therapeutic option
      for end-stage respiratory failure in cystic fibrosis. However, airway
      complications remain a major cause of morbidity and mortality in these patients,
      serious airway complications like bronchopleural fistula (BPF) are rare, and
      their management is very difficult. CASE PRESENTATION: A 47-year-old man with end
      stage respiratory failure due to cystic fibrosis underwent bilateral sequential
      lung transplantation. Severe post-operative bleeding occurred due to dense
      intrapleural adhesions of the native lungs. He was re-explored and packed leading
      to satisfactory haemostasis. He developed a bronchopleural fistula on the 14th
      post-operative day. The fistula was successfully repaired using pericardial and
      intercostal vascular flaps with veno-venous extracorporeal membrane oxygenator
      (VV-ECMO) support. Subsequently his recovery was uneventful. CONCLUSION: The
      combination of pedicled intercostal and pericardial flaps provide adequate
      vascular tissue for sealing a large BPF following LTx. Veno-venous ECMO allows a
      feasible bridge to recovery.

PMID- 17550622
TI  - Targeting services to reduce social inequalities in utilisation: an analysis of
      breast cancer screening in New South Wales.
AB  - BACKGROUND: Many jurisdictions have used public funding of health care to reduce
      or remove price at the point of delivery of services. Whilst this reduces an
      important barrier to accessing care, it does nothing to discriminate between
      groups considered to have greater or fewer needs. In this paper, we consider
      whether active targeted recruitment, in addition to offering a 'free' service, is
      associated with a reduction in social inequalities in self-reported utilization
      of the breast screening services in NSW, Australia. METHODS: Using the 1997 and
      1998 NSW Health Surveys we estimated probit models on the probability of having
      had a screening mammogram in the last two years for all women aged 40-79. The
      models examined the relative importance of socio-economic and geographic factors
      in predicting screening behaviour in three different needs groups - where needs
      were defined on the basis of a woman's age. RESULTS: We find that women in higher
      socio-economic groups are more likely to have been screened than those in lower
      groups for all age groups. However, the socio-economic effect is significantly
      less among women who were in the actively targeted age group. CONCLUSION: This
      indicates that recruitment and follow-up was associated with a modest reduction
      in social inequalities in utilisation although significant income differences
      remain.

PMID- 17550623
TI  - Pre-operative risk scores for the prediction of outcome in elderly people who
      require emergency surgery.
AB  - BACKGROUND: The decision on whether to operate on a sick elderly person with an
      intra-abdominal emergency is one of the most difficult in general surgery. A
      predictive risk-score would be of great value in this situation. METHODS: A
      Medline search was performed to identify those predictive risk-scores relevant to
      sick elderly patients in whom emergency surgery might be life-saving. RESULTS:
      Many of the risk scores for surgical patients include the operative findings or
      require tests which are not available in the acute situation. Most of the
      relevant studies include younger patients and elective surgery. The Glasgow
      Aneurysm Score and Hardman Index are specific to ruptured aortic aneurysm while
      the Boey Score and the Hacetteppe Score are specific to perforated peptic ulcer.
      The Reiss Index and Fitness Score can be used pre-operatively if the elements of
      the score can be completed in time. The ASA score, which includes a significant
      element of subjective clinical judgement, can be augmented with factors such as
      age and urgency of surgery but no test has a negative predictive value sufficient
      to recommend against surgical intervention without clinical input. CONCLUSION:
      Risk scores may be helpful in sick elderly patients needing emergency abdominal
      surgery but an experienced clinical opinion is still essential.

PMID- 17550624
TI  - Myocardial segment-specific model generation for simulating the electrical action
      of the heart.
AB  - BACKGROUND: Computer models of the electrical and mechanical actions of the
      heart, solved on geometrically realistic domains, are becoming an increasingly
      useful scientific tool. Construction of these models requires detailed
      measurement of the microstructural features which impact on the function of the
      heart. Currently a few generic cardiac models are in use for a wide range of
      simulation problems, and contributions to publicly accessible databases of
      cardiac structures, on which models can be solved, remain rare. This paper
      presents to-date the largest database of porcine left ventricular segment
      microstructural architecture, for use in both electrical and mechanical
      simulation. METHODS: Cryosectioning techniques were used to reconstruct the
      myofibre and myosheet orientations in tissue blocks of size ~15 x 15 x 15 mm,
      taken from the mid-anterior left ventricular freewall, of seven hearts. Tissue
      sections were gathered on orthogonal planes, and the angles of intersection of
      myofibres and myosheets with these planes determined automatically with a
      gradient intensity based algorithm. These angles were then combined to provide a
      description of myofibre and myosheet variation throughout the tissue, in a form
      able to be input to biophysically based computational models of the heart.
      RESULTS: Several microstructural features were common across all hearts.
      Myofibres rotated through 141 +/- 18 degrees (mean +/- SD) from epicardium to
      endocardium, in near linear fashion. In the outer two-thirds of the wall sheet
      angles were predominantly negative, however, in the inner one-third an abrupt
      change in sheet angle, with reversal in sign, was seen in six of the seven
      hearts. Two distinct populations of sheets with orthogonal orientations often co
      existed, usually with one population dominating. The utility of the tissue
      structures was demonstrated by simulating the passive and active electrical
      responses of two of the tissue blocks to current injection. Distinct patterns of
      electrical response were obtained in the two tissue blocks, illustrating the
      importance of testing model based predictions on a variety of tissue
      architectures. CONCLUSION: This study significantly expands the set of geometries
      on which models of cardiac function can be solved.

PMID- 17550625
TI  - Expression pattern analysis of transcribed HERV sequences is complicated by ex
      vivo recombination.
AB  - BACKGROUND: The human genome comprises numerous human endogenous retroviruses
      (HERVs) that formed millions of years ago in ancestral species. A number of loci
      of the HERV-K(HML-2) family are evolutionarily much younger. A recent study
      suggested an infectious HERV-K(HML-2) variant in humans and other primates.
      Isolating such a variant from human individuals would be a significant finding
      for human biology. RESULTS: When investigating expression patterns of specific
      HML-2 proviruses we encountered HERV-K(HML-2) cDNA sequences without proviral
      homologues in the human genome, named HERV-KX, that could very well support
      recently suggested infectious HML-2 variants. However, detailed sequence
      analysis, using the software RECCO, suggested that HERV-KX sequences were
      produced by recombination, possibly arising ex vivo, between transcripts from
      different HML-2 proviral loci. CONCLUSION: As RT-PCR probably will be
      instrumental for isolating an infectious HERV-K(HML-2) variant, generation of
      "new" HERV-K(HML-2) sequences by ex vivo recombination seems inevitable. Further
      complicated by an unknown amount of allelic sequence variation in HERV-K(HML-2)
      proviruses, newly identified HERV-K(HML-2) variants should be interpreted very
      cautiously.

PMID- 17550626
TI  - Reconstruction of the kinetochore: a prelude to meiosis.
AB  - In eukaryotic organisms, chromosomes are spatially organized within the nucleus.
      Such nuclear architecture provides a physical framework for the genetic
      activities of chromosomes, and changes its functional organization as the cell
      moves through the phases of the cell cycle. The fission yeast Schizosaccharomyces
      pombe provides a striking example of nuclear reorganization during the transition
      from mitosis to meiosis. In this organism, centromeres remain clustered at the
      spindle-pole body (SPB; a centrosome-equivalent structure in fungi) during
      mitotic interphase. In contrast, during meiotic prophase, centromeres dissociate
      from the SPB and telomeres cluster to the SPB. Recent studies revealed that this
      repositioning of chromosomes is regulated by mating pheromone signaling. Some
      centromere proteins disappear from the centromere in response to mating
      pheromone, leading to dissociation of centromeres from the SPB. Interestingly,
      mating pheromone signaling is also required for monopolar orientation of the
      kinetochore which is crucial for proper segregation of sister chromatids during
      meiosis. When meiosis is induced in the absence of mating pheromone signaling,
      aberrant chromosome behaviors are observed: the centromere proteins remain at the
      centromere; the centromere remains associated with the SPB; and sister chromatids
      segregate precociously in the first meiotic division. These aberrant chromosome
      behaviors are all normalized by activating the mating pheromone signaling
      pathway. Thus, action of mating pheromone on the centromere is important for
      coherent behavior of chromosomes in meiosis. Here we discuss repositioning and
      reconstruction of the centromere during the transition from mitosis to meiosis,
      and highlight its significance for proper progression of meiosis.

PMID- 17550627
TI  - Ultrasound measurement of joint cartilage thickness in large and small joints in
      healthy children: a clinical pilot study assessing observer variability.
AB  - BACKGROUND: Loss of joint cartilage is a feature of destructive disease in JIA.
      The cartilage of most joints can be visualized with ultrasonography (US). Our
      present study focuses on discriminant validity of US in children. We studied
      reproducibility between and within a skilled and a non-skilled investigator of US
      assessment of cartilage thickness in small and large joints in healthy children.
      METHODS AND RESULTS: In 11 healthy children (5 girls/6 boys), aged 9.6 years (9.3
      10 years), 110 joints were examined. Cartilage thickness of the right and left
      hip, knee, ankle, 2nd metacarpophalangeal (MCP), and 2nd proximal interphalangeal
      (PIP) joint independently. The joints were examined twice, two days apart by a
      skilled and a non-skilled investigator. Mean cartilage thickness in the five
      joints was: hip 2.59 +/- 0.41, knee 3.67 +/- 0.64, ankle 1.08 +/- 0.31, MCP 1.52
      +/- 0.27 and PIP 0.73 +/- 0.15 mm. We found the same mean differences in CTh of
      0.6 mm in the inter-observer part with regard of the PIP joint. Within
      investigators (intra-observer), the smallest mean difference of CTh was found in
      the MCP joint with -0.004 (skilled) and 0.013 mm (non-skilled). CONCLUSION: We
      found the level of agreement between observers within a 95% Confidence Interval
      in assessment of cartilage thickness in hip-, knee-, ankle-, MCP-, and PIP joints
      in healthy children. Observer variability seems not to relate to joint size but
      to the positioning of the joints and the transducer. These factors seem to be of
      major importance for reproducible US measurements. The smallest difference in
      measurement of cartilage thickness between observers was found in the PIP joint,
      and within observers in the MCP joint and it seems that using EULAR standard US
      guidelines is feasible for a pediatric setting. The use of US in children is
      promising. Studies on larger groups of children are needed to confirm the
      validation and variability of US in children as well as determining the smallest
      detectable difference of US measures.

PMID- 17550628
TI  - Pediatric Rheumatology - a continuation of Pediatric Rheumatology Online Journal.

PMID- 17550629
TI  - Reactive arthritis of the temporomandibular joints and cervical spine in a child.
AB  - BACKGROUND: Temporomandibular joint (TMJ) arthritis is frequently seen in
      children with chronic arthritis. It has rarely been described in a non-infectious
      acute setting. We report a case of reactive arthritis isolated to the TMJs and
      cervical spine. CASE PRESENTATION: A 6-year-old Native American boy hospitalized
      for treatment of lymphadenitis and aseptic meningitis had an incidental brain
      magnetic resonance imaging (MRI) finding of effusions in the TMJs, as well as the
      atlanto-occipital and C1-C2 articulations. Repeat TMJ and cervical spine MRI four
      weeks later showed resolution of effusions. Reactive TMJ arthritis has been
      previously reported in adults but not in children. CONCLUSION: This report
      represents the first pediatric case of reactive arthritis isolated to the
      cervical spine and TMJs. Arthritis of the TMJ should be considered in the
      differential diagnosis of children with reactive arthritides.

PMID- 17550630
TI  - Homocysteine and lipid profile in children with Juvenile Idiopathic Arthritis.
AB  - BACKGROUND: An increased concentration of plasma homocysteine (Hcy) has toxic
      effects on vascular endothelium. This seems to be a risk factor of cardiovascular
      disease, premature stroke and venous thrombosis. The risk is higher in
      coincidence with other factors like chronic diseases and familiar
      hypercholesterolemia. The aim of our study was to evaluate plasma Hcy
      concentration in patients with juvenile idiopathic arthritis (JIA) and its
      correlation with methotrexate (MTX) therapy, serum folate and B12 vitamin, and
      hyperlipidemia. METHODS: Fifty-one patients (37 females; mean age 11.3 years,
      range 2.3-17 years) with JIA and 52 healthy controls (42 females; mean age 12.5
      years; range 3-18 years) were included in the study. Thirty-two patients were
      using weekly MTX (mean doses: 0.1-1 mg/kg). For statistical analysis both JIA and
      control groups were distributed in three subgroups according to age (3 - 7, 8 -
      12 and 13 - 18 years). The laboratory investigation included measurement of
      erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), plasma Hcy, serum
      folate, vitamin B12, triglycerides, total cholesterol, high-density lipoprotein
      (HDL), low-density lipoprotein (LDL) and very low-density lipoprotein (VLDL). For
      data analysis, we considered raised Hcy values >or= 12.56 micromol/L, which
      corresponds to the 90th percentile observed in the control group. RESULTS: The
      mean plasma Hcy concentration was 9.3 +/- 3.16 micromol/L in JIA patients and 8.9
      +/- 2.42 micromol/L in healthy controls (p = 0.615). Higher concentration of Hcy
      was observed in the subgroup of 13 - 18 years (patients and controls, p < 0.001).
      We did not find correlation between MTX use and plasma Hcy concentration. With
      regard to vitamin B12 concentration, we detected normal values in both patients
      and controls while serum folate concentration was higher in patients (p < 0.001).
      With regard to the lipidogram, lower concentration of HDL was found in patients
      (p = 0.007) and higher levels of VLDL (p = 0.014) and triglycerides (p = 0.001)
      were observed in controls. We did not observe correlation among plasma Hcy
      concentration, clinical findings, ESR and CRP. CONCLUSION: JIA patients do not
      present significant increased concentration of Hcy despite the use of MTX,
      probably due to the folate supplementation. The mild abnormalities in the
      lipidogram may reflect a current concern with diet and health.

PMID- 17550631
TI  - Growing pains in children.
AB  - We review the clinical manifestations of "growing pains", the most common form of
      episodic childhood musculoskeletal pain. Physicians should be careful to adhere
      to clear clinical criteria as described in this review before diagnosing a child
      with growing pain. We expand on current theories on possible causes of growing
      pains and describe the management of these pains and the generally good outcome
      in nearly all children.

PMID- 17550632
TI  - Clinical characteristics of children with Juvenile Systemic Sclerosis: follow-up
      of 23 patients in a single tertiary center.
AB  - BACKGROUND: Juvenile systemic sclerosis (JSS) is a multisystem connective tissue
      disease characterized by skin fibrosis and internal organ involvement. It has a
      low prevalence, even in a tertiary facility setting. The purpose of the present
      study is to describe and analyze the clinical and laboratory characteristics of a
      group of children with JSS followed in a single center. METHODS: Clinical charts
      of children with a diagnosis of JSS who were seen at a tertiary referral center
      between 1995 and 2005 were reviewed. Clinical features were recorded and
      analysed. RESULTS: Twenty-three patients who met preliminary classification
      criteria for JSS were included. Age at first symptom attributable to JSS was 6 (1
      14) years, The first symptom attributable to JSS was Raynaud's phenomenon in 14
      cases. Proximal sclerosis (23 patients, 100%), sclerodactyly (21, 91%), Raynaud's
      phenomenon (19, 83%), and periungual capillaropathy (17, 74%) were the most
      consistent clinical findings during follow-up. Respiratory involvement occurred
      in two thirds of our patients, and it manifested as dyspnea as well as abnormal
      imaging and/or pulmonary function tests; pulmonary hypertension was an infrequent
      finding. Dysphagia was the commonest gastrointestinal symptom (9 patients, 39%).
      The most frequent musculoskeletal symptom was arthralgia (14 children, 6%);
      symmetrical arthritis was found in 8 (35%) patients. Periungual capillary
      abnormalities were evident during physical examination in 17 children;
      capillaroscopy revealed abnormalities in all 19 examined patients. ANA were
      present in 17 (74%) children: homogeneous pattern was the most frequent (8
      patients), nucleolar (5) and speckled (4) were less common. CONCLUSION: Raynaud's
      phenomenon heralds the beginning of the disease. Capilaroscopy is a major
      adjuvant in the diagnosis, since autoantibody determination may not offer
      sensitive and specific markers. Skin and vascular manifestations are the most
      common clinical features, while internal organ involvement is more rare.
      Cardiopulmonary disease is the most frequent visceral involvement, leading to
      significant morbidity.

PMID- 17550633
TI  - Rhupus arthropathy as the presenting manifestation in Juvenile SLE: a case
      report.
AB  - An 8.5-year-old girl was referred with swelling of both knees lasting for two
      years. ANA was found as negative. She was diagnosed as oligoarticular JIA. After
      two years of follow-up, thrombocytopenia was detected during routine screening.
      Her ANA and anti ds-DNA antibodies also became positive, with low levels of C3
      and C4. She was diagnosed as Juvenile SLE, meeting the criteria cytopenia,
      positive immunoserology (anti dsDNA), positive ANA test, and four years of
      ongoing chronic arthritis, so called as "rhupus arthropathy". We should be aware
      of the several initial incomplete presentations of lupus in children. We should
      be careful in monitoring the serious manifestations of the disease in juvenile
      lupus patients with rhupus arthropathy, and consider the poor response to
      standard disease modifying agents.

PMID- 17550634
TI  - Review for the generalist: evaluation of anterior knee pain.
AB  - Anterior knee pain is common in children and adolescents. Evaluation and
      management is challenging and requires a thorough history and physical exam, and
      understanding of the pediatric skeleton. This article will review common causes
      of chronic anterior knee pain in the pediatric population with a focus on
      patellofemoral pain.

PMID- 17550635
TI  - Improving adherence to medical regimens for juvenile rheumatoid arthritis.
AB  - Poor adherence to medical regimens can compromise the efficacy of treatments for
      children and adolescents with juvenile rheumatoid arthritis (JRA). The purpose of
      this review is to describe medical regimens for the treatment of JRA and the
      rates of adherence to these regimens. We also summarize and critically the few
      research studies aimed at improving adherence to regimens for JRA. Finally, we
      summarize strategies for enhancing adherence in clinical practice.

PMID- 17550639
TI  - Glycine receptors of A-type ganglion cells of the mouse retina.
AB  - A-type ganglion cells of the mouse retina represent the visual channel that
      transfers temporal changes of the outside world very fast and with high fidelity.
      In this study we combined anatomical and physiological methods in order to study
      the glycinergic, inhibitory input of A-type ganglion cells. Immunocytochemical
      studies were performed in a transgenic mouse line whose ganglion cells express
      green fluorescent protein (GFP). The cells were double labeled for GFP and the
      four alpha subunits of the glycine receptor (GlyR). It was found that most of the
      glycinergic input of A-type cells is through fast, alpha1-expressing synapses.
      Whole-cell currents were recorded from A-type ganglion cells in retinal whole
      mounts. The response to exogenous application of glycine and spontaneous
      inhibitory postsynaptic currents (sIPSCs) were measured. By comparing glycinergic
      currents recorded in wildtype mice and in mice with specific deletions of
      GlyRalpha subunits (Glra1spd-ot, Glra2-/-, Glra3-/-), the subunit composition of
      GlyRs of A-type ganglion cells could be further defined. Glycinergic sIPSCs of A
      type ganglion cells have fast kinetics (decay time constant tau = 3.9 +/- 2.5 ms,
      mean +/- SD). Glycinergic sIPSCs recorded in Glra2-/- and Glra3-/- mice did not
      differ from those of wildtype mice. However, the number of glycinergic sIPSCs was
      significantly reduced in Glra1spd-ot mice and the remaining sIPSCs had slower
      kinetics than in wildtype mice. The results show that A-type ganglion cells
      receive preferentially kinetically fast glycinergic inputs, mediated by GlyRs
      composed of alpha1 and beta subunits.

PMID- 17550640
TI  - Visual function in regenerating teleost retina following surgical lesioning.
AB  - Regeneration of the teleost retina following surgical extirpation of 25% to 100%
      of the neural retina was investigated in goldfish (Carrasius auratus) and sunfish
      (Lepomis cyanellus). The retina will regenerate following removal of up to 95% of
      the neural retina, however complete extirpation prevented regeneration. Visual
      sensitivity was assessed by examining components of the electroretinogram (ERG)
      and the dorsal light reflex (DLR) during regeneration. B-wave amplitudes in the
      experimental eyes increased throughout the study and central connections were
      reestablished as indicated by the progressive improvement in the dorsal light
      reflex. The recovery of visual function was closely correlated with retinal
      regeneration. Visual recovery progressed more slowly than following complete
      cytotoxic destruction of the mature retina (Mensinger & Powers, 1999) because the
      surgery removed a large number of the pluripotent cell population and restricted
      the number and distribution of regenerating foci.

PMID- 17550641
TI  - Variability in the firing of retinal ganglion cells of goldfish: a review.
AB  - The isolated retina of the goldfish has proven a valuable resource for studying
      the variability of firing of retinal ganglion cells. Three major areas of study
      are considered here: the variability of maintained discharges, the correlated
      firing of neighboring ganglion cells, and the variability of responses to light.
      The sources of variability, its relationship to retinal processing, and its
      possible functional role in perception are examined through these three aspects
      of variability. The results are related to similar studies in mammals (mainly
      cats). This retrospective is biased toward my studies over 30 years.

PMID- 17550636
TI  - Functional polarity of dendrites and axons of primate A1 amacrine cells.
AB  - The A1 cell is an axon-bearing amacrine cell of the primate retina with a
      diffusely stratified, moderately branched dendritic tree (approximately 400
      microm diameter). Axons arise from proximal dendrites forming a second
      concentric, larger arborization (>4 mm diameter) of thin processes with bouton
      like swellings along their length. A1 cells are ON-OFF transient cells that fire
      a brief high frequency burst of action potentials in response to light (Stafford
      & Dacey, 1997). It has been hypothesized that A1 cells receive local input to
      their dendrites, with action potentials propagating output via the axons across
      the retina, serving a global inhibitory function. To explore this hypothesis we
      recorded intracellularly from A1 cells in an in vitro macaque monkey retina
      preparation. A1 cells have an antagonistic center-surround receptive field
      structure for the ON and OFF components of the light response. Blocking the ON
      pathway with L-AP4 eliminated ON center responses but not OFF center responses or
      ON or OFF surround responses. Blocking GABAergic inhibition with picrotoxin
      increased response amplitudes without affecting receptive field structure. TTX
      abolished action potentials, with little effect on the sub-threshold light
      response or basic receptive field structure. We also used multi-photon laser
      scanning microscopy to record light-induced calcium transients in morphologically
      identified dendrites and axons of A1 cells. TTX completely abolished such calcium
      transients in the axons but not in the dendrites. Together these results support
      the current model of A1 function, whereby the dendritic tree receives synaptic
      input that determines the center-surround receptive field; and action potentials
      arise in the axons, which propagate away from the dendritic field across the
      retina.

PMID- 17550642
TI  - Restoration of visual function following optic nerve regeneration in bluegill
      (Lepomis macrochirus) x pumpkinseed (Lepomis gibbosus) hybrid sunfish.
AB  - Simple (dorsal light reflex) and complex (predator-prey interactions) visually
      mediated behaviors were used concurrently with morphological examination to
      assess restoration of visual function following optic nerve crush in bluegill
      (Lepomis macrochirus) x pumpkinseed (Lepomis gibbosus) hybrid sunfish.
      Regenerating optic nerve axons projected into the stratum opticum-stratum
      fibrosum et griseum superficiale by week 2, the stratum griseum centrale by week
      4, and stratum album centrale by week 6. Initial projections into the laminae
      were diffuse and less stratified compared to controls. By week 12, the projection
      pattern of regenerating nerve fibers closely resembled the innervation of normal
      tecta. Visual improvements were correlated with increasing projections into the
      tectum. The dorsal light reflex improved from a 45 degrees vertical deviation
      following nerve crush to 4.5 degrees by week 16. Initial predator-prey
      interactions were exclusively mediated by the control eye. As regeneration
      progressed, there was a gradual expansion of the visual field. The reaction
      distance and attack angles within the visual field of the experimental eye were
      initially less than controls, however, these differences disappeared by week 10.
      Improvements in visual function were closely correlated with an increase of
      regenerating ganglion cell axons into the optic tectum indicating sufficient
      synaptogenesis to mediate both simple and complex visual behavior.

PMID- 17550643
TI  - Using modelling to assess the risk of malarial infection during the dry season,
      on a local scale in an endemic area of rural Burkina Faso.
AB  - Mathematical modelling has been used to assess the level of malarial
      transmission, during the dry season, in Nouna province, in north-western Burkina
      Faso. The data used were collected, at four sites (one semi-urban and three
      rural), from 867 children aged 6-60 months who were randomly selected. Almost all
      of the children (850) completed the follow-up, which involved the active
      detection of malaria (i.e. febrile, smear-positive malarial infection) throughout
      a single dry season (December 2003-May 2004). Light traps were used to sample the
      local populations of Anopheles vectors, in order to estimate the daily biting
      rate. The mathematical model was then used to simulate the incidence of malaria,
      which was compared with the observed incidence. At all four study sites, new
      cases of malaria were observed throughout the dry season, although the level of
      transmission was low. The monthly incidence of malaria estimated using the
      mathematical model was very close to the observed incidence. The fit was
      sensitive to daily mosquito survival and daily human parasite clearance. In Nouna
      province, effective interventions to prevent malaria should not be confined to
      the rainy season but must continue throughout the year. The focus should be on
      the clearance of parasitaemias, by the use of effective drugs, and on decreasing
      vector survival, by the use of vector-control methods.

PMID- 17550644
TI  - The in-vitro susceptibilities of Ghanaian Plasmodium falciparum to antimalarial
      drugs.
AB  - In Ghana in 2004 (when choroquine was still the nationally recommended drug for
      the first-line treatment of malaria), the sensitivities, to chloroquine,
      amodiaquine, quinine, mefloquine, artesunate and halofantrine, of 60 Plasmodium
      falciparum isolates from two ecologically distinct areas of the country were
      assessed in vitro. The aim was to make available, to policy-makers, the field
      based evidence needed to review the national strategy for malaria treatment. Drug
      susceptibilities were explored using the standardized protocol of the
      Antimalarial Drug Resistance Network. Although 32 of the P. falciparum isolates
      evaluated (56.1% of the 57 isolates successfully investigated for their
      susceptibility to choroquine) showed resistance to chloroquine and two showed
      slightly reduced sensitivity to amodiaquine, all the isolates were sensitive to
      mefloquine, artesunate, quinine and halofantrine. The median inhibitory
      concentrations (IC(50)) of chloroquine were positively correlated with those of
      quinine (r=0.4528; P=0.0008) but not those of any of the other drugs
      investigated. The IC(50) of amodiaquine and artesunate were also positively
      correlated (r=0.3703; P=0.0067). These results provide evidence of the presence,
      in Ghana, of P. falciparum isolates that are highly resistant to chloroquine but
      generally sensitive to most of the other antimalarial drugs commonly used in the
      country. Partly in consequence of these observations, the recommended first-line
      treatment for malaria in Ghana was changed to an amodiaquine-artesunate
      combination in January 2005.

PMID- 17550645
TI  - Evaluation of PCR-RFLP (based on ITS-1 and HaeIII) for the detection of
      Leishmania species, using Greek canine isolates and Jordanian clinical material.
AB  - It is possible to detect and distinguish Leishmania parasites using PCR-RLFP - a
      combination of PCR and analysis of the fragment-length polymorphism seen when the
      amplicons are digested with one or more restriction enzymes. In the present
      study, clinical samples from 24 Jordanians suspected to have cutaneous
      leishmaniasis and cultures set up using leishmanial parasites from five Greek
      dogs were investigated using PCR, in which the internal-transcribed-spacer-1
      (ITS1) region of the parasites' ribosomal-RNA gene was amplified, followed by
      HaeIII digestion of the resulting amplicons. The cultures, which were all
      maintained in Leibowitz L-15 medium with 20% foetal calf serum, were each
      investigated as serial dilutions. Using the PCR-RLFP analysis, each culture was
      identified as L. donovani and each was found positive for this parasite with a
      mean sensitivity of 66%-100% (depending on the culture dilution tested), a
      specificity of 100%, a mean positive predictive value of 100%, and a negative
      predictive value of 74.6%-100%. When simulated clinical samples, created by
      mixing human blood with known numbers of L. donovani promastigotes, were
      investigated, the PCR-RFLP gave optimal results (with a value of 100% each for
      sensitivity, specificity and positive and negative predictive values). When the
      real clinical samples (25 lesion aspirates and 20 samples of peripheral blood
      from 24 Jordanian patients) were investigated using the molecular method, 20
      (84%) of the patients were found to have lesion aspirates that were PCR-RFLP
      positive for L. major (although, by microscopy, only six were found to have
      amastigote-positive lesion aspirates). None of the blood samples from the
      Jordanian patients, however, was found PCR-positive.

PMID- 17550646
TI  - Cercarial dermatitis in central India: an emerging health problem among tribal
      communities.
AB  - Although cercarial dermatitis is an emerging disease world-wide, cases of such
      dermatitis may often go undiagnosed, especially in communities that are affected
      by various skin infections. Between August 2001 and July 2002, 1336 individuals
      from tribal villages in central India were examined for dermatitis. Skin
      scrapings were collected and examined for Sarcoptes scabiei and each subject's
      response to antiscabies treatment was recorded. Freshwater snails were collected
      from the local ponds used for bathing, and examined for cercariae. The recorded
      prevalence of dermatitis ranged between 2.1% and 12.5% during the study year,
      peaking at the end of winter (February-March) and during the rainy season (August
      October). Snail positivity for cercariae peaked in the rainy season. The
      prevalence and the severity of dermatitis were both higher in children than in
      adults. As most recorded cases of dermatitis were associated with a rash that
      developed soon after bathing in the local pond, all the skin scrapings were
      negative for itch mites, and the response to antiscabies treatment was poor, most
      if not all of the dermatitis observed was probably cercarial. Cercarial
      dermatitis therefore appears to be a significant health problem among the tribal
      populations of central India.

PMID- 17550647
TI  - PCR-based differentiation of Fasciola species (Trematoda: Fasciolidae), using
      primers based on RAPD-derived sequences.
AB  - The zoonotic liver flukes Fasciola hepatica and F. gigantica co-exist in parts of
      Africa and Asia. The two species have similar life-cycles but different
      transmission characteristics. Although the identification of adult Fasciola to
      species level is traditionally based on differences in size and shape, recent
      studies have demonstrated this method to be unreliable. Species of Fasciola can
      be distinguished by staining and comparing the morpho-anatomy of the gut and
      ovaries or by iso-enzyme analysis but such approaches are time-consuming and
      require specialist skills. Two primer sets, based on RAPD-derived sequences from
      English F. hepatica and Ghanaian F. gigantica, can now be used, in two separate
      PCR, to distinguish F. hepatica from F. gigantica. When the PCR were used to
      investigate 10 flukes (five from the U.K. and five from Peru) morpho-anatomically
      identified as F. hepatica and 10 (five from Ghana and five from Sudan) morpho
      anatomically identified as F. gigantica, all 20 flukes were correctly identified
      to species level. The PCR were validated using 175 flukes collected, over a 12
      year period, from different countries and both cattle and sheep.

PMID- 17550648
TI  - Children and adolescents infected with Wuchereria bancrofti in Greater Recife,
      Brazil: a randomized, year-long clinical trial of single treatments with
      diethylcarbamazine or diethylcarbamazine-albendazole.
AB  - In filariasis-endemic areas beyond sub-Saharan Africa, the World Health
      Organization's recommended strategy for interrupting transmission of the
      causative parasites is annual, single-dose, mass treatment with a combination of
      diethylcarbamazine (DEC; given at 6 mg/kg) and albendazole (ALB; given at 400 mg)
      for 4-6 years (the minimum estimated life-span of the adult parasites). In an
      open, hospital-based, randomized and controlled trial, with a blinded evaluation
      of outcome, 82 children and adolescents from Recife, all with Wuchereria
      bancrofti microfilaraemias, were given either DEC alone (6 mg/kg) or the same
      dose of DEC combined with ALB (at 400 mg/patient). Every 90 days for 1 year after
      the single treatment, each patient was checked for microfilaraemia by the
      filtration of up to 5 ml of venous blood collected at night. One year post
      treatment, 16 (39%) of the 41 patients given DEC alone and 20 (49%) of the 41
      given DEC-ALB were found microfilaraemic (relative risk=0.8, with a 95%
      confidence interval of 0.49-1.31) and the corresponding geometric mean levels of
      microfilaraemia were 2.0% and 1.8% of the levels recorded immediately pre
      treatment, respectively (P>0.05). In terms of the prevalences and intensities of
      microfilaraemia, therefore, the addition of ALB to the DEC appeared to offer no
      significant benefit.

PMID- 17550649
TI  - Maternal transmission of Wolbachia in Phlebotomus papatasi (Scopoli).
AB  - Attempts have been made to transfer Wolbachia from infected to uninfected,
      laboratory-reared Phlebotomus papatasi, through mating, and to determine whether
      the incompatibility phenotype could be expressed through crosses between infected
      and uninfected flies. In order to test for the intraspecific transmission of
      Wolbachia in crosses between infected females and uninfected males, or those
      between uninfected females and infected males, a PCR based on Wolbachia -specific
      wsp primers was used to test the progeny of each cross and, subsequently, 50
      individual flies from the F(3) generation. All the individual flies tested from
      the F(1) progeny of the crosses between infected males and uninfected females
      were found to be uninfected. In the crosses involving infected females and
      uninfected males, however, Wolbachia were found in the progeny of five matings
      out of the 23 that produced viable eggs. In the F(3), Wolbachia were not detected
      in any of the individuals resulting from the cross between uninfected females and
      infected males but they were detected in 52% (26) of the 50 tested individuals
      resulting from the cross between infected females and uninfected males. No
      evidence of cytoplasmic incompatibility (CI) was observed in any of the crosses.
      The absence of CI expression and relatively low frequencies of maternal
      transmission could hamper the potential use of Wolbachia in a transgenic strategy
      for the control of leishmaniases.

PMID- 17550650
TI  - Seasonal and altitudinal variations in fly density and their association with the
      occurrence of trachoma, in the Gurage zone of central Ethiopia.
AB  - In the Gurage zone of central Ethiopia, the association between fly density and
      the occurrence of trachoma has been investigated across varying altitudes. The
      seasonal pattern of fly density in the area was also explored. When, over short
      sampling periods (10 min/child indoors and 10 min/child outdoors), hand nets were
      used to collect flies from the eyes of children aged 2-8 years, only Musca
      sorbens and M. domestica were caught. Almost all of the 13,147 'eye-seeking'
      flies collected came from villages at low (<2000 m; 40.7%) or mid altitudes (2200
      2500 m; 58.6%) with only 0.7% of them caught in the high-altitude villages
      investigated (at >3000 m). Musca sorbens predominated outdoors and M. domestica
      indoors. Almost all (99.3%) of the eye-seeking M. sorbens collected were caught
      outdoors whereas most (76.7%) of the M. domestica were caught indoors (P<0.0001
      for each). The median numbers of flies caught, per child, per 10-min collection,
      in the low-, mid- and high-altitude villages were 9.5, six and zero,
      respectively, for M. sorbens, and eight, three and zero, respectively, for M.
      domestica. The altitudinal trends in these numbers of 'eye-seeking' flies matched
      those in the prevalences of active trachoma among children aged 1-10 years, which
      were high in the villages at low (81.6%) and mid altitude (78.7%) but much lower
      (1.7%) in the high-altitude villages. In conclusion, trachoma is a common disease
      of public-health importance only in the low- and mid-altitude villages in the
      Gurage zone, where there are large numbers of eye-seeking flies, and not in the
      villages that lie >3000 m above sea level, where there is a dearth of such flies.

PMID- 17550651
TI  - Entomological evaluation of three brands of manufactured insecticidal nets and of
      nets conventionally treated with deltamethrin, after repeated washing.
AB  - The present study evaluated the efficacy and wash resistance of three types of
      commercial, deltamethrin-treated nets (PermaNet, Yorkool and A-Z nets) - that
      their manufacturers claimed to be long-lasting insecticidal nets (LLIN) - and
      those of nets conventionally treated with deltamethrin, at either 23-27 mg/m(2)
      (using one K-O Tab tablet/net) or 46-54 mg/m(2) (using two K-O Tab tablets/net).
      The nets were tested unwashed or after being washed, by hand or machine, five or
      15 times. After each wash, the nets were dried vertically on a line, in the
      shade, for 8 h. Insecticidal activity was assessed, using two types of bio-assay
      and wild-caught female Anopheles stephensi, as mean median knock-down times and
      as mortality 24 h after a 3-min exposure. For each type of nets tested, the
      insecticidal activity of the unwashed nets was greater than that of the nets
      washed five washes, and that of the nets washed five times was greater than that
      of the nets washed 15 times, with the latter decline considerably greater than
      the former. The pattern of decrease, however, differed with net type. The
      PermaNet and A-Z nets generally had the highest insecticidal activity, and,
      overall, the Yorkool nets did not perform significantly better than the
      conventional nets treated with 23-27 mg deltamethrin/m(2). Although washing with
      detergents can clearly remove insecticide from the fibres of all types of treated
      nets, the consequent loss of activity varies with net type. After 15 washes, the
      PermaNet nets showed higher insecticidal activity than any other net type but
      there is still scope for the manufacturer of the PermaNet nets to improve wash
      resistance.

PMID- 17550652
TI  - Rainfall and malaria transmission in north-eastern India.

PMID- 17550653
TI  - The detection of Trypanosoma cruzi in Triatoma infestans: comparison of a PCR
      based assay with microscopical examination.

PMID- 17550654
TI  - Controlled release of paclitaxel from biodegradable unsaturated poly(ester
      amide)s/poly(ethylene glycol) diacrylate hydrogels.
AB  - Biodegradable hydrogels (FPBe-G) were synthesized by the photopolymerization of
      two precursors: FPBe, a fumurate-based unsaturated poly(ester amide) (UPEA), and
      poly(ethylene glycol) diacrylate (PEG-DA). Depending on the feed ratio of these
      two precursors, the resultant FPBe-G hydrogels showed different crosslinking
      levels of network structure, mesh sizes (xi) and matrix morphology. When a
      lipophilic drug, paclitaxel, was preloaded into FPBe-G hydrogels, the two-month
      drug-release kinetics from FPBe-G hydrogels in both pure PBS buffer and alpha
      chymotrypsin media were measured. The paclitaxel-preloaded FPBe-G hydrogels in a
      alpha-chymotrypsin solution had significantly faster drug release rate than the
      corresponding hydrogels in a pure PBS buffer due to an enzyme catalyzed
      biodegradation of FPBe-G hydrogels. Sustained paclitaxel releases over a two
      month period without initial burst release were also achieved by using hydrogels
      having certain feed ratios of hydrogel precursors. These paclitaxel release data
      correlated well with the molecular mesh size (xi), molecular weight between cross
      links (M(c)) and matrix morphological structure of FPBe-G hydrogels.

PMID- 17550655
TI  - Repair of mandibular defects using MSCs-seeded biodegradable polyester porous
      scaffolds.
AB  - PLLA, PLA-PEG and PLGA porous scaffolds with pore size ranging from 100 to 250
      microm and porosity over 85% were fabricated by a solution-casting/salt-leaching
      method. The porous structure and porosity of the scaffold were mainly dependent
      on volume fraction and size of the porogens of NaCl particles. The effects of the
      polymeric materials on the cell culture behavior and bone formation in vitro in
      their scaffolds were studied. In vitro cell culture in the scaffolds of the three
      polymers demonstrated that mesenchymal stem cells (MSCs) had a good adhesion and
      spread. The composite matrixes cultured for several days possessed preliminary
      functions of tissue-engineering bone, with signs of the calcium knur formation
      and the expression of osteocalcin and collagen I in mRNA, especially that of PLA
      PEG and PLGA. These cell-loaded porous scaffolds showed effective repair of
      mandibular defect of rabbits in vivo. Contrastive experiments demonstrated that
      the MSCs/PLGA scaffold owned better ability facilitating for the MSCs
      proliferation, differentiation and defect repair. These composite scaffolds can
      be a potential effective tool for treating mandibular and other bone defects.

PMID- 17550656
TI  - Synthesis and properties of star oligo/poly(trimethylene carbonate)s with cholic
      acid moieties as cores.
AB  - Star oligo/poly(trimethylene carbonate)s with cholic acid moieties as cores were
      synthesized by ring-opening polymerization of trimethylene carbonate (TMC)
      initiated by cholic acid with hydroxyl groups. The molecular weights of the star
      oligomers/polymers were controlled by adjusting the feed ratio of the initiator
      cholic acid to the monomer TMC. The star oligo/poly(trimethylene carbonate)s were
      characterized by Fourier transform infrared spectroscopy (FT-IR), (1)H nuclear
      magnetic resonance spectroscopy ((1)H-NMR) and combined size-exclusion
      chromatography and multiangle laser light scattering (SEC-MALLS) analysis. The
      water contact angles of the star oligo/poly(trimethylene carbonate)s were
      measured. Using 3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide
      (MTT) assay, the star oligo/poly(trimethylene carbonate) was proved to have a low
      cytotoxicity. A microsphere drug-delivery system based on a star polymer was
      fabricated and its in vitro drug release property was studied.

PMID- 17550657
TI  - Studies on the preparation and antibacterial properties of quaternized
      polyethyleneimine.
AB  - Quaternized polyethyleneimine (QPEI) was prepared via two types of macromolecular
      reactions, tertiary amination reaction and quaterization, and its chemical
      structure was characterized using infrared and UV spectroscopy. In this paper,
      the antibacterial properties of QPEI were mainly investigated by using
      Escherichia coli as model bacterium and with the colony count method. The effects
      of the cationic degree and pH value of the medium on the antibacterial properties
      of QPEI were examined. The antibacterial mechanism of QPEI was also explored
      using enzyme activity measurement methods, in which the enzyme activity of two
      enzymes, beta-D-galactosidase and TTC-dehydrogenase, were measured. The
      experiments show that QPEI possesses outstanding antibacterial activity because
      of combination effect of the antibacterial groups on the macromolecular chains.
      The antibacterial ratio reached 100% for bacterium suspensions of 10(9) CFU/ml
      with a polymer concentration of 15 mg/l for a contact time of 4 min. The cationic
      degree influences the antibacterial ability of QPEI greatly, and the higher the
      cationic degree, the stronger the antibacterial activity. The experimental data
      indicated that the pI of the E. coli protein is probably 4.5. When pH > 4.5, the
      antibacterial activity of QPEI increases with increasing pH, and when pH > 6 the
      antibacterial ratio reaches a maximum and remain nearly constant. The enzyme
      activity measurement results reveal that the antibacterial action of QPEI is
      based on a sterilization process. Similar to the small molecular quaternary
      ammonium salt, QPEI causes cell death by disrupting cell membranes and releasing
      the intracellular contents.

PMID- 17550658
TI  - Dual-targeting non-viral vector based on polyethylenimine improves gene transfer
      efficiency.
AB  - Polyethylenimine (PEI) is the polymer most commonly used for transferring
      plasmids into eukaryotes, but its gene-transfer efficiency is lower compared to
      viral vectors. Receptors targeting PEI combined with ligands can enhance
      efficiency of gene transfer into the corresponding receptor-positive cells. Using
      the double-receptor-mediated pathway of viral infection, in this study we
      synthesized a novel non-viral vector based on PEI combined with two peptides
      recognizing FGF receptors (peptide YC25) and integrins (peptide CP9) on the cell
      surface. The dual targeting vector showed a physicochemical character similar to
      that of PEI, such as pDNA formation, particle size, zeta potential and lower
      toxicity. In vitro gene transfer showed that the dual-receptor targeted vector
      (YC25-PEI-CP9) exhibited a markedly higher transgene efficiency in cell lines
      with positive expression of FGF receptors and integrins, compared with single
      peptide-modified PEI or unmodified PEI. In the cells with only integrin-positive
      expression, YC25-PEI-CP9 mediated a higher transgene expression than PEI but
      lower than CP9-PEI. The corresponding free peptides could inhibit the transgene
      efficiency of the peptide-coupled PEI. In vivo gene transfer in tumor-bearing
      nude mice also demonstrated that the dual-targeting vectors showed a
      significantly enhanced transfection efficiency in tumors with positive expression
      of FGF receptors and integrins. The synthesized polymer YC25-PEI-CP9 has the
      prospect to act as a novel kind of non-viral vector in gene therapy.

PMID- 17550659
TI  - Synthesis of HMDI-based segmented polyurethanes and their use in the manufacture
      of elastomeric composites for cardiovascular applications.
AB  - For short-term cardiovascular application, segmented polyurethanes (SPUs) based
      on 4,4-methylenebis(cyclohexyl isocyanate) (HMDI), polytetramethylenglycol (PTMG)
      and 1,4-butanediol (BD) were synthesized and characterized by spectroscopy (FT
      IR, (1)H-NMR) and thermal (TGA, DMA, DSC) and mechanical techniques. The
      segmented nature of the SPUs was not easily established by spectroscopic means;
      however, TGA allowed the quantification of the rigid segments content by the
      significant mass loss between 348 and 356 degrees C. The alpha transition was
      detected by DMA and related to the T(g) of the soft segments at -50 degrees C,
      while DSC showed the presence of an endothermic transition above 80 degrees C
      attributed to the melting of rigid segments. Two types of composites were
      prepared using the synthesized SPUs and Lycra (either T162B or T162C). The first
      one consisted of a two layers casting laminated while the second one was a
      classic unidirectional fibre-reinforced material. Laminate composites prepared
      with SPU containing 23.9% and 33.9% of rigid segments and Lycra T162C exhibited a
      higher tensile modulus but lower tensile strength than composites prepared with
      Tecoflex SG-80A (39.7% of rigid segments). The energy of adhesion between layers
      on these composites ranged from 475 to 2150 J. Fibre-reinforced SPUs exhibited
      higher moduli than the two layer laminated composites with increasing amounts of
      rigid segments in the matrix and by increasing Lycra T162C content (up to 10%).
      This behaviour was explained by SEM, which showed a good fibre-matrix bonding.

PMID- 17550660
TI  - Prefabricated tracheal prosthesis with partial biodegradable materials: a
      surgical and tissue engineering evaluation in vivo.
AB  - Large and circumferential tracheal defects remain at this time an unsolved
      problem for reconstructive surgery. Many types of prosthetic and tissue grafts
      have been used but with limited comfortable results. Major complications are
      anastomotic dehiscence, graft ischemia and stenosis due to the poor
      vascularization of the prosthetic complex. We studied the in vivo behaviour of a
      prefabricated flap composed of a partially bioresorbable tracheal prosthesis and
      an arterio-venous vascular carrier. The prosthesis was made of a tubular skeleton
      of knitted Dacron (20 microm porosity) embedded within a bioresorbable poly
      lactic-co-glycolic acid polymer (PLA(75)GA(25)) covering both sides. Fifteen New
      Zealand White rabbits were divided in three groups, depending on the time of
      examination (30, 90 and 180 days post-implantation). The prosthesis was implanted
      in the visceral space of the neck using the common carotid trunk and the internal
      jugular vein as vascular pedicle. The histological, immunohistochemical, and ESEM
      analyses of collected samples, showed a time-dependent process of tissue
      neoformation and neovascularization on the prosthetic material with a significant
      increase from 30 to 90 days post-implantation. In contrast, there was no
      statistically significant difference in the fibrovascular connective deposition
      from 90 to 180 days. This finding indicated the three months time as the best
      period for the tissue deposition and consequent hypothetical orthotopic
      transplantation of the prosthesis. Further in vivo studies are intended to
      confirm the results.

PMID- 17550661
TI  - Immobilisation of horseradish peroxidase onto monodisperse poly(glycidyl
      methacrylate) microspheres.
AB  - The aim of this study was to immobilize horseradish peroxidase (HRP) onto
      poly(glycidyl methacrylate) (PGMA) microspheres. In this study, PGMA particles
      were synthesised by dispersion polymerization from the glycidyl methacrylate
      (GMA) monomer. The monomer conversion value was determined to be 89% by weight.
      The first step comprised opening of the epoxide rings and formation of amine
      groups on the particle surfaces. The characterised particles were used as micro
      carriers for the immobilisation of HRP. Glutaraldehyde, as bifunctional reactive,
      has been used as the spacer arm in the second step of the covalent binding
      method. The optimum immobilisation conditions found are as follows:
      immobilisation time 10 min, pH 7.2, temperature 25 degrees C, initial enzyme
      concentration 0.05 mg/ml. Kinetic parameters of native and immobilised enzyme,
      such as K(m) and V(max) values, have been calculated 2.33 mmol/l and 0.670 mmol/l
      per s for the native enzyme and for the immobilised enzyme 69.13 mmol/l and 0.175
      mmol/l per s, respectively. The HRP immobilised microparticules were used to
      purify a textile bleaching solution in which excess H(2)O(2) remains.

PMID- 17550662
TI  - Correlation of proliferation, morphology and biological responses of fibroblasts
      on LDPE with different surface wettability.
AB  - In order to find a correlation between cell adhesion, growth and biological
      response with different wettability, NIH/3T3 fibroblast cells were cultured on
      plasma-treated low-density polyethylene (LDPE) film generated with radio
      frequency. Different surface wettabilities (water contact angle 90-40 degrees )
      were created by varying the duration of plasma treatment between 0 and 15 s,
      respectively. Growth and proliferation rate of cells on LDPE surfaces was
      evaluated by MTT assay, and cell morphology, by means of spreading and adhesion,
      was characterized by scanning electron microscopy (SEM). The expression of
      particular genes in cells contacted on films with different wettability was
      analyzed by RT-PCR. Using the MTT assay, we confirmed that the amount of cell
      adhesion was higher on surface of film with a water contact angle of 60 degrees
      than with other water contact angle. Also, the proliferation rate of cells was
      highest with a water contact angle of 60 degrees . It was confirmed by SEM that
      the morphology of cells adhered with a water contact angle of 50-60 degrees was
      more flattened and activated than on other surfaces. Furthermore, c-fos mRNA in
      cells showed maximum expression on the film with contact angle range of 50-60
      degrees and c-myc mRNA expressed highly on the film with a contact angle of 50
      degrees . Finally, p53 gene expression increased as wettability increase. These
      results indicate that a water contact angle of the polymer surfaces of 50-60
      degrees was suitable for cell adhesion and growth, as well as biological
      responses, and the surface properties play an important role for the morphology
      of adhesion, growth and differentiation of cells.

PMID- 17550663
TI  - Tissue-compatible and adhesive polyion complex hydrogels composed of amphiphilic
      phospholipid polymers.
AB  - To investigate the tissue adhesive function of a hydrogel composed of
      biocompatible amphiphilic polymers, polymers with various architectures were
      prepared from 2-methacryloyloxyethyl phosphorylcholine (MPC), electrolyte
      monomers and hydrophobic n-butyl methacrylate (BMA). A polyion complex (PIC)
      hydrogel was formed within a few minutes after aqueous solutions containing the
      cationic and anionic MPC polymers were mixed. Provided the electrical charge of
      the cationic and anionic MPC polymers was approximately balanced, the PIC
      hydrogel existed stably in a large amount of aqueous medium. The results of the
      fluorescence study of the MPC polymers suggested that dissociation was suppressed
      and that the electrostatic interaction was enhanced in the block and graft
      polymers compared to the random polymers. This is due to the strategically
      designed architectures and the hydrophobic BMA units. Based on the results of the
      cytotoxicity test, the cytotoxicity of the MPC polymers was lower than that of
      glutaraldehyde, a cross-linker contained in aldehyde-type tissue adhesives. The
      cationic MPC polymers demonstrated higher cytotoxicity compared to the anionic
      ones, which demonstrated no significant cytotoxicity at examined concentrations.
      The tissue adhesion of the PIC hydrogels was evaluated with a dura incision
      model. The results indicated that the tissue adhesion strength of the PIC
      hydrogel was lower than that of a commercially available fibrin glue. However,
      the tissue adhesion strength increased with an increase in the polymer
      concentration and could be controlled by the water content of the hydrogel.
      Although further investigation of the biocompatibility of the PIC hydrogels and
      control of the water content is crucial, it can be concluded that the PIC
      hydrogels formed by the amphiphilic MPC polymers can be promising tissue
      adhesives which demonstrate properties according to the architectures and
      chemical structures.

PMID- 17550665
TI  - The Quality and Outcomes Framework: what have you done to yourselves?

PMID- 17550666
TI  - A truly global partnership for health.

PMID- 17550667
TI  - Lost in the global sum? Professional and practice development in primary care
      after the new general practice contract.

PMID- 17550668
TI  - The relationship between social deprivation and the quality of primary care: a
      national survey using indicators from the UK Quality and Outcomes Framework.
AB  - BACKGROUND: The existence of health inequalities between least and most socially
      deprived areas is now well established. AIM: To use Quality and Outcomes
      Framework (QOF) indicators to explore the characteristics of primary care in
      deprived communities. DESIGN OF STUDY: Two-year study. SETTING: Primary care in
      England. METHOD: QOF data were obtained for each practice in England in 2004-2005
      and 2005-2006 and linked with census derived social deprivation data (Index of
      Multiple Deprivation scores 2004), national urbanicity scores and a database of
      practice characteristics. Data were available for 8480 practices in 2004-2005 and
      8264 practices in 2005-2006. Comparisons were made between practices in the least
      and most deprived quintiles. RESULTS: The difference in mean total QOF score
      between practices in least and most deprived quintiles was 64.5 points in 2004
      2005 (mean score, all practices, 959.9) and 30.4 in 2005-2006 (mean, 1012.6). In
      2005-2006, the QOF indicators displaying the largest differences between least
      and most deprived quintiles were: recall of patients not attending appointments
      for injectable neuroleptics (79 versus 58%, respectively), practices opening > or
      =45 hours/week (90 versus 74%), practices conducting > or = 12 significant event
      audits in previous 3 years (93 versus 81%), proportion of epileptics who were
      seizure free > or = 12 months (77 versus 65%) and proportion of patients taking
      lithium with serum lithium within therapeutic range (90 versus 78%). Geographical
      differences were less in group and training practices. CONCLUSIONS: Overall
      differences between primary care quality indicators in deprived and prosperous
      communities were small. However, shortfalls in specific indicators, both clinical
      and non-clinical, suggest that focused interventions could be applied to improve
      the quality of primary care in deprived areas.

PMID- 17550669
TI  - Quality of clinical primary care and targeted incentive payments: an
      observational study.
AB  - BACKGROUND: Payments for recorded evidence of quality of clinical care in UK
      general practices were introduced in 2004. AIM: To examine the relationship
      between changes in recorded quality of care for four common chronic conditions
      from, 2003 to 2005, and the payment of incentives. DESIGN OF STUDY: Retrospective
      observational study comparing incentivised and non-incentivised indicators of
      quality of care. SETTING: Eighteen general practices in England. METHOD: Medical
      records were examined for 1156 patients. The percentage of eligible quality
      indicators achieved for each patient was assessed in 2003 and 2005. Twenty-one
      quality indicators referred to asthma and hypertension: six subject to and 15 not
      subject to incentive payments. Another 15 indicators referred to depression and
      osteoarthritis which were not subject to incentive payments. RESULTS: A
      significant increase occurred for the six indicators linked to incentive
      payments: from 75% achieved in 2003 to 91% in 2005 (change = 16%, 95% confidence
      interval [CI] = 10 to 22%, P <0.01). A significant increase also occurred for 15
      other indicators linked to 'incentivised conditions'; 53 to 64% (change = 11%,
      95% CI = 6 to 15%, P <0.01). The 'non-incentivised conditions' started at a lower
      achievement level, and did not increase significantly: 35 to 36% (change = 2%,
      95% CI = -1 to 4%, P = 0.19). CONCLUSION: The introduction of financial
      incentives was associated with substantial apparent quality improvement for
      incentivised conditions. For non-incentivised conditions, quality did not appear
      to improve. Patients with non-incentivised conditions may be at risk of poorer
      quality care.

PMID- 17550670
TI  - Management of type 2 diabetes with multiple oral hypoglycaemic agents or insulin
      in primary care: retrospective cohort study.
AB  - BACKGROUND: Intensive glycaemic control can reduce the risk of microvascular
      complications in people with type 2 diabetes. AIM: To examine the extent of
      monitoring and glycaemic control of patients with type 2 diabetes prescribed oral
      agents and/or insulin, and to investigate transition to insulin. DESIGN OF STUDY:
      Retrospective cohort study. SETTING: A total of 154 general practices in the UK
      contributing to the DIN-LINK database between 1995 and 2005. METHOD: People with
      type 2 diabetes were identified using Read codes and prescribing data. Outcome
      measures were: glycaemic monitoring and control on multiple oral agents and/or
      insulin, and transition to insulin. RESULTS: A total of 14 824 people with type 2
      diabetes were prescribed multiple oral agents concurrently, of whom 5064 (34.16%)
      had haemoglobin A(1c) (HbA(1c)) assessments 6 months before and following
      initiation of their last oral therapy. Mean HbA(1c) before therapy was 9.07%,
      which dropped to 8.16% following therapy (mean difference 0.91%, 95% confidence
      interval [CI] = 0.86 to 0.95, P <0.0001). Of the patients with HbA(1c)
      assessments, 3153 (62.26%) had evidence of poor glycaemic control following
      therapy. Median time to insulin for patients prescribed multiple oral agents was
      7.7 years (95% CI = 7.4 to 8.5 years); 1513 people began insulin during the study
      and had HbA(1c) assessments 6 months before and following insulin. Mean HbA(1c)
      before insulin was 9.85% (standard deviation [SD] 1.96%) which decreased by
      1.34%, (95% CI = 1.24% to 1.44%) following therapy, but 1110 people (73.36%)
      still had HbA(1c) > or =7.5%. CONCLUSION: Many people with type 2 diabetes
      received inadequate monitoring and had poor glycaemic control. Intensive
      management is required to reduce the risk of microvascular complications.

PMID- 17550671
TI  - Health beliefs of African-Caribbean people with type 2 diabetes: a qualitative
      study.
AB  - BACKGROUND: There is evidence that African-Caribbean people with diabetes have
      poorer outcomes than other individuals with diabetes. It is not fully understood
      why this happens. AIM: To gain an understanding of how health beliefs influence
      the way African-Caribbean people with diabetes manage their illness. DESIGN OF
      STUDY: Qualitative study using one-to-one interviews. SETTING: Inner-city
      Nottingham during 2003-2004. METHOD: A purposive sample of 16 African-Caribbean
      people with type 2 diabetes. Participants took part in semi-structured in-depth
      interviews which were audio-taped recorded and transcribed. Transcripts were
      analysed for emergent themes and validity was checked by an independent
      researcher and through discussion with a local community group. Data were managed
      using NVivo software. RESULTS: Participants were strongly influenced by memories
      of growing up in the Caribbean, migration to the UK, and friends' and families'
      accounts of diabetes, as well as their own experiences of the illness. Knowledge
      and understanding of diabetes was sometimes poor. There was some mistrust in the
      value of advice and treatment offered by professionals and a preference for
      natural treatments. Health professionals were generally praised but some
      interviewees felt that the NHS did not cater properly for black people. Insulin
      treatments were feared and diet- or tablet-controlled diabetes was seen by some
      as a mild form that did not warrant serious concern. CONCLUSIONS: These findings
      have implications for how some people manage their diabetes and how diabetes care
      is delivered to the African-Caribbean community.

PMID- 17550672
TI  - Management of endometriosis in general practice: the pathway to diagnosis.
AB  - BACKGROUND: The prevalence of endometriosis is estimated to be around 10%.
      Diagnosis is through visualisation of the lesions, mostly via laparoscopy.
      Studies reveal that there is an average delay in the diagnosis of endometriosis
      of between 8 and 12 years. Little is known about the reasons for delays in
      diagnosis women's experiences of primary care prior to diagnosis. AIM: To
      investigate women's experiences of endometriosis from first presentation to
      diagnosis. DESIGN OF STUDY: Retrospective analysis of data collected from primary
      care records in four general practices. SETTING: General practice in south-east
      England. METHOD: Women with a Read Code diagnosis of endometriosis were recruited
      to the study. Details of consultations, investigations, and referrals related to
      endometriosis were recorded from the notes. Data were analysed using descriptive
      statistics. RESULTS: The prevalence of endometriosis in women aged over 16 years
      was 1.44%. A third of women had consulted their GP six or more times before being
      diagnosed. Ultrasound was frequently requested by GPs, but was helpful in
      diagnosing endometriosis in only 10.6% of women who underwent a scan. Thirty-nine
      per cent of women were referred to gynaecologists two or more times before a
      positive diagnosis was made. The median time from first presentation with
      symptoms to diagnosis was 9.0 years (interquartile range = 4.5-13.5 years).
      CONCLUSION: Repeated consultations and negative investigations contribute to a
      median delay of 9.0 years before diagnosis of endometriosis. Further research
      into GPs' interpretation of symptoms and patients' experiences of negative
      investigations and consultations may lead to a more positive outcome for women
      with this condition.

PMID- 17550674
TI  - Diabetes care and the new GMS contract: the evidence for a whole county.
AB  - The aim of this study was to assess the impact of the Quality and Outcomes
      Framework (QOF) of the new GP contract on diabetes care in Shropshire, which has
      a total population of approximately 460 000. The mean percentage of patients
      achieving each of the quality indicators in each practice in Shropshire, before
      and after the implementation of the QOF was calculated. All 16 867 patients with
      diabetes from all 66 Shropshire practices were included. There were significant
      improvements in the percentage of patients achieving targets for all quality
      indicators between April 2004 to March 2006 (P<0.001).

PMID- 17550673
TI  - Quality of life in smokers: focus on functional limitations rather than on lung
      function?
AB  - BACKGROUND: The Global Initiative for Chronic Obstructive Lung Disease (GOLD)
      classification of severity of chronic obstructive pulmonary disease (COPD) is
      based solely on obstruction and does not capture physical functioning. The
      hypothesis that the Medical Research Council (MRC) dyspnoea scale would correlate
      better with quality of life than the level of airflow limitation was examined.
      AIM: To study the associations between quality of life in smokers and limitations
      in physical functioning (MRC dyspnoea scale) and, quality of life and airflow
      limitation (GOLD COPD stages). DESIGN: Cross-sectional study. SETTING: The city
      of IJsselstein, a small town in the centre of The Netherlands. METHOD: Male
      smokers aged 40-65 years without a prior diagnosis of COPD and enlisted with a
      general practice, participated in this study. Quality of life was assessed by
      means of a generic (SF-36) and a disease-specific, questionnaire (QOLRIQ).
      RESULTS: A total of 395 subjects (mean age 55.4 years, pack years 27.1) performed
      adequate spirometry and completed the questionnaires. Limitations of physical
      functioning according to the MRC dyspnoea scale were found in 25.1% (99/395) of
      the participants and airflow limitation in 40.2% (159/395). The correlations of
      limitations of physical functioning with all quality-of-life components were
      stronger than the correlations of all quality-of-life subscales with the severity
      of airflow limitation. CONCLUSION: In middle-aged smokers the correlation of
      limitations of physical functioning (MRC dyspnoea scale) with quality of life was
      stronger than the correlation of the severity of airflow limitation with quality
      of life. Future staging systems of severity of COPD should capture this and not
      rely on forced expiratory volume in one second (FEV1) alone.

PMID- 17550675
TI  - Spurious trends in coronary heart disease incidence: unintended consequences of
      the new GP contract?
AB  - Comparisons of the same patient data in 2004 and 2006 downloads of the DIN-LINK
      UK primary care database demonstrated unexpected differences in the rates of
      coronary heart disease between the datasets. Incidence rates were lower between
      1996-2003 in the new (2006) download. Patient record checks demonstrated that
      coronary heart disease codes had been removed in the new download during the run
      up to the new contract. Planners need to be aware of such issues when evaluating
      trends in CHD or other similar conditions.

PMID- 17550676
TI  - Confidentiality in the waiting room: an observational study in general practice.
AB  - An ethnographic study using overt non-participatory observation was used to
      investigate confidentiality breaches in 13 GP practice reception and/or waiting
      areas in Lincolnshire. Staff and patient behaviours were observed for 2 hours.
      Aspects of management systems and physical environment were also thematically
      analysed. Forty-four instances occurred where patient-identifiable information
      was overheard. Of these instances, 22 were initiated by staff, 22 by patients, 33
      face-to-face, and 10 from telephone conversations. Breaches included name and
      address, symptoms, conditions, or test results. Interaction between systems and
      physical environment in relation to 'attention focus', 'sound' and 'layout',
      increased the likelihood of breach of confidentiality. Further research on the
      patient perspective is recommended.

PMID- 17550677
TI  - The New Millennium Palliative Care Project (2000-2003): the impact of specialised
      GP advisors.
AB  - This study describes a novel type of support for GPs caring for patients dying at
      home: the establishment and evaluation of a telephone advisory service for GPs,
      run by GPs with a special interest in palliative care (GPwSIs) in the Netherlands
      2000-2003. A growing number of GPs called for advice, 10% during out of hours.
      Prognosis of the patients was generally short (days to weeks in 70% of cases).
      Most advice sought by GPs concerned symptom management and on evaluation, 85% of
      the GPs followed the advice.

PMID- 17550678
TI  - Time trends in the incidence of peptic ulcers and oesophagitis between 1994 and
      2003.
AB  - This study examined time trends in the incidence of peptic ulcers and
      oesophagitis, and the prescription of acid-inhibiting drugs in the period 1994
      2003. Data were retrieved from records in general practices in Flanders, Belgium.
      The incidence of duodenal ulcers decreased by two-thirds and the incidence of
      gastric ulcers halved, the incidence of oesophagitis initially increased and
      decreased slowly later on. In 10 years the proportion of patients taking proton
      pump inhibitors rose sixfold while the proportion taking H(2) antagonists
      remained stable.

PMID- 17550679
TI  - Handshakes and consultations.

PMID- 17550680
TI  - Edzard Ernst and complementary medicine.

PMID- 17550681
TI  - Developing primary care treatment of depression.

PMID- 17550682
TI  - Computer records.

PMID- 17550683
TI  - QOF vs NICE.

PMID- 17550684
TI  - Palliative care: a task for everyone.

PMID- 17550687
TI  - Patient record access--the time has come!

PMID- 17550689
TI  - Blair's legacy: a 'patient-centred' NHS.

PMID- 17550693
TI  - [The contribution of the user to prevent and to control type 2 diabetes].

PMID- 17550694
TI  - [Quality of life in patients with continuous ambulatory peritoneal dialysis].
AB  - OBJECTIVE: To evaluate different aspects of the quality of life of patients with
      continuous ambulatory peritoneal dialysis, using the survey SF-36 (Medical
      Outcomes Study 36-Short Form Health Survey). METHODOLOGY: A cross-sectional study
      was carried out with patients older than 18 years having chronic renal failure
      and being registered in the continuous ambulatory peritoneal dialysis program in
      the last three months. A sample size of 48 patients was estimated. The version
      1.1 of the SF-36 survey previously adapted for Mexican people was used to
      evaluate quality of life. RESULTS: Forty-eight patients were included, among
      which 52% were males, the mean of age was 45 years old. All eight domains of
      health were analyzed. The role limitations due to physical health showed the
      lower score (mean = 19.79; men: 13, women: 27.1) while mental health showed the
      higher (mean = 61.66; men: 59.68 women: 63.83).

PMID- 17550695
TI  - [High tibial dome osteotomy complications in genu varum patients].
AB  - OBJECTIVE: To identify if pre-surgical risk factors or the surgical technique
      were associated with the complications of the osteotomy in genu varus patients.
      METHODOLOGY: A case-control study was conducted in patients that underwent Maquet
      proximal tibial osteotomy for treatment of genu varus between January and
      December 2003. The risk factors were the following: age 50 or more years old,
      comorbidity such as type 2 diabetes, hypertension, rheumatoid arthritis,
      overweight and obesity (BMI > or = 25 and > or = 30), duration of ischemia longer
      than 60 min and local pain. Cases were those who developed one or more
      complications. Descriptive and inferential statistical analyses were performed.
      RESULTS: One hundred and thirty-four patients were included, among which 53% had
      complications. None of the risk factors were statistically significant (p >
      0.05). CONCLUSIONS: None of pre-surgical risk factors were associated with the
      complications of osteotomy; therefore, these could be attributable to the
      surgical technique. It is necessary to outweigh the temporary benefits of the
      tibial osteotomy versus the increase in the risk of complications when performing
      total knee arthroplasty.

PMID- 17550696
TI  - [Differences of risk factors for peripheral arterial disease in type 2 diabetes
      patients in urban and suburban populations].
AB  - OBJECTIVES: To determine the prevalence of peripheral arterial disease (PAD) in
      type 2 diabetes patients and to measure the strength of the association of
      selected risk factors. METHODOLOGY: A cross-sectional study including two hundred
      and fifty-two type 2 diabetes patients older than 40 years was conducted in three
      family medicine clinics, one clinic located within the city and two clinics in
      the suburb. PAD was diagnosed by Doppler pulsed in the patients with an ankle/arm
      index < 0.9. CLINICAL VARIABLES: Serum cholesterol and triglycerides levels, body
      mass index (BMI), waist-hip index (WHI), blood pressure (BP) and fasting blood
      glucose average of the last six months. To ascertain the differences in the
      prevalence of PAD, chi(2) test was used; t test was used for quantitative
      variables; and to estimate the risks the odds ratios were calculated. RESULTS:
      Among urban population the prevalence of PAD was of 25.6% while for those living
      in the suburb was 9.8 % (p = 0.002). Serum levels of blood glucose and
      cholesterol were lower in the latter (p = 0.01 and p = 0.001 respectively). PAD
      was associated with serum blood glucose levels higher than 140 mg/dL (OR = 3.1;
      95% CI: 1-9.7); total cholesterol higher than 200 mg/dL (OR = 2.8; 95% CI: 1.1
      7.4); proteinuria (OR = 4.9; 95% CI: 1.7-30.6) and blood pressure higher than
      140/90 mm Hg (OR = 2.11; 95% CI: 1.08-4.14). CONCLUSIONS: Prevalence of PAD was
      higher in type 2 diabetes patients receiving care in urban clinics when compared
      to those cared for at suburban family medicine clinics and its corresponding risk
      factors showed significant values.

PMID- 17550697
TI  - [Perception of undergraduate medical students of the educational environment at
      Instituto Mexicano del Seguro Social].
AB  - OBJECTIVE: To ascertain the perception of third and fourth year medical students
      and interns (fifth year) about the educational environment during the clinical
      education phase and during the internship at Instituto Mexicano del Seguro Social
      (IMSS). METHODOLOGY: A questionnaire with 120 items was developed to evaluate
      whether IMSS educational environment encourages reflection and criticism among
      medical students and interns. The highest possible score of the questionnaire was
      240 points. A t test was used to compare the score of the students who were
      classified according to the term in which they were enrolled. 1997 medical
      students and 1075 interns from 46 IMSS clinical settings answered the previously
      validated questionnaire. RESULTS: Seventy percent of the students considered that
      the educational environment was not very favorable for reflection and criticism;
      19% perceived it as favorable and 11% as unfavorable. The median score of third
      and fourth year medical students, was 134.9 (range 80-193; p = 0.27), interns'
      score was 130.4 (range 80-208; p = 0.001). The perception of the medical students
      in clinical settings other than Mexico City was less unfavourable (median 132.8;
      range 63.5-208); p = 0.003). CONCLUSIONS: apparently, the occupational
      environment influences the educational environments where the courses take place.
      As long as the students advance in their courses and get involved in clinical
      practice, their perception of the educational environment becomes unfavorable.

PMID- 17550698
TI  - [Pediatric traumatic injuries requiring hospitalization. A serious health
      problem].
AB  - OBJECTIVE: To identify the age-adjusted prevalence of pediatric traumatic
      injuries requiring hospitalization. METHODOLOGY: A retrospective, observational
      cross-sectional study was carried out in the pediatric trauma department at the
      Hospital Magdalena de las Salinas of Instituto Mexicano del Seguro Social. Data
      from all pediatric patients hospitalized between January 1998 and December 2005
      due to traumatic injuries were included. RESULTS: 5,987 patients analyzed; 66.9%
      were male, 46.0% were children; 31.3% preschoolers; 18.2% adolescents and 4.4%
      infants. Regarding the injuries, 48.2% were injured at home, 74.8% suffered
      closed fractures, particularly among preschoolers and children; 12.4% suffered
      open fractures. Craneoencephalic trauma occurred in 34.2%, mostly in children and
      adolescents. Among preschoolers and children supracondylar fractures of the
      humerus occurred in 23.0%; the commonest was type IV (94%); physeal fractures
      occurred in 2.6% and lesions due to battered children were in 0.31%. As to the
      treatment, infants and preschoolers were treated through cast immobilization;
      closed reduction and internal fixation was common in school-age children (27%)
      while open reduction and external fixation was used in adolescents (26.8%).
      CONCLUSIONS: Preventive measures should be encouraged in the group with the
      highest prevalence of traumatic injuries requiring hospital care: male school-age
      children who predominantly suffer craneoencephalic trauma and supracondylar
      fractures of the humerus.

PMID- 17550699
TI  - [Small group discussion to promote self-learning].
AB  - OBJECTIVE: To emphasize the influence of small groups discussion to promote self
      learning. METHODOLOGY: Educational strategies aimed at promoting active
      participation were designed, and evaluated through its effect in developing
      aptitude to read critically. The experimental group (EG) participated in a three
      phased strategy (individual assignment, small group discussion and plenary); the
      control group participated in a two-phased strategy (individual assignment and
      plenary). Subjects in both groups were randomly selected. Previously, an
      instrument to measure the capability to read critically educational theory texts
      was developed and validated. The duration and the contents were equal in both
      strategies. RESULTS: At the baseline, there were no differences between groups.
      After participating in the strategies, both groups showed significant progress.
      CG increased its score from 16 to 33 and the EC from 20 to 48 (p < 0.02).
      CONCLUSIONS: Small group discussion proved to be effective to increase the
      capability to read critically educational theory texts, thus it use should be
      considered when implementing educational strategies aimed at promoting active
      participation.

PMID- 17550700
TI  - [Users satisfaction with dental care services provided at IMSS].
AB  - OBJECTIVE: To determine users' satisfaction with dental care services provided at
      Instituto Mexicano del Seguro Social in Veracruz. METHODOLOGY: An epidemiological
      survey was conducted in 14 family medicine clinics located in the northern part
      of the state of Veracruz. The clinics were selected by stratified-random
      sampling. All users older than 20 years seeking medical or dental care services
      were interviewed; previously, their informed consent was obtained. We used the 6
      items United Kingdom dental care satisfaction questionnaire (Spanish version)
      where question number four evaluates user satisfaction. RESULTS: From October to
      December 2005, 3601 users were interviewed. We excluded 279 questionnaires
      because the age of the interviewees was <20 years. The final analysis included
      3322 interviews (92%); 73% were female with an average age of 45 +/- 16 years
      old. 82% were satisfied with dental care services and 91% never felt like making
      a complaint. Waiting time of less than 30 minutes and last visit to the dentist
      in the last year were the only variables related to satisfaction (p = 0.0001).
      CONCLUSION: There is a high level of satisfaction regarding dental care services
      among Mexican Institute of Social Security users. However, it would be possible
      to increase the level of satisfaction if the waiting time is reduced and the
      number of dental care users attending twice a year increases.

PMID- 17550701
TI  - [Breast cancer. Evidence and recommendations for the timely detection in primary
      care].
AB  - The steady increase of cases and toll of deaths due to breast cancer in the last
      decades has prompted to analyze in depth current screening methods and their
      contributions to decrease mortality rates. A literature review was performed at
      the Ovid-Medline, Cochrane, Synergy, Medic Latina, Science Direct, EBSCO-e
      Journal services. The review focused on the epidemiology of breast cancer, its
      risk factors and the benefits and limitations of current screening methods. The
      literature review had the aim to contribute in updating primary care
      practitioners concerning effective screening methods to timely detect breast
      cancer.

PMID- 17550702
TI  - [Asymptomatic bacteriuria among pregnant women. An underestimated threat].
AB  - BACKGROUND: Urinary tract infection is a common pregnancy complication.
      Asymptomatic bacteriuria (AB) can trigger the development of serious
      complications affecting both the mother and the fetus. OBJECTIVE: Determine the
      frequency of AB among pregnant women attending to antenatal care at the family
      medicine clinic number 1 of the Instituto Mexicano del Seguro Social, located in
      Ciudad Obregon, Sonora. METHODOLOGY: A longitudinal study was carried out from
      September to December 2004. Seventy-two 72 pregnant women with gestational age of
      24 weeks or less were followed up during four months. All pregnant women were
      selected by a non-probabilistic method. Every patient had a monthly urine culture
      during the follow up period. RESULTS: Among the 72 pregnant women, 16.7%
      developed symptomatic urinary infections during the follow-up and 25% had at
      least one positive urine culture without urinary symptoms, being classified as
      AB, thus receiving treatment. Frequency of positive urine cultures was common at
      first and fourth months of follow-up. CONCLUSION: Urine culture is an important
      component of prenatal care, and helps in identifying a significant number of
      urinary tract infections that would go otherwise undetected.

PMID- 17550703
TI  - [Clinical guide for diagnosis, treatment and prevention of overweight and obesity
      in children].
AB  - The prevalence of overweight has significantly increased thorough the world and
      Mexico is not an exception considering that the National Survey of Nutrition
      (1999) showed that 19.5% of scholar children in Mexico have overweight and other
      survey from Mexico City (ENURBAL, 2002) have shown that 17% in the same range of
      age are obese. Therefore, this clinical guide pretends to be an instrument for
      supporting the professionals of health for the diagnosis, treatment and
      prevention of obesity in children using the levels of medical attention. It is
      known that the treatment is difficult and it requires a full multidisciplinary
      team of professionals and that the key of prevention is the modification of the
      sedentary lifestyle and the decrease of energy intake. This guide was elaborated
      by pediatricians working in nutrition in public and university institutions,
      family and general physicians and pediatricians with private practice.

PMID- 17550704
TI  - [Systemic juvenile rheumatoid arthritis].

PMID- 17550706
TI  - [Medical justification of the eight-hour shift work].
AB  - The 8-hour shift work is one of the main achievements of the organized workers.
      International solidarity with United States miners, who were massacred in Chicago
      in 1886, and the aftermath of World War I promoted the establishment of 8-hour
      shift work in many countries. In Mexico, the 1917 Social Rights Declaration
      adhered to this position under the idea that the excessive workload above the 8
      hour limit had negative effects on the health of workers; nevertheless, this
      statement seems to be sustained only by testimonies, anecdotal opinions and/or by
      the logic and common sense that then prevailed. For this reason, a literature
      review was carried out in search for the evidence supporting this apparently
      immovable length of the shift work. The globalization of the economy and the
      tendency towards flexibility and deregulation of current contractual
      relationships, are the new challenges that the 8-hour shift work is facing.

PMID- 17550707
TI  - [Verbal autopsy in cervico-uterine cancer].
AB  - BACKGROUND: Verbal autopsy (VA) is a standardized method for investigating causes
      of death. Currently, the Mexican Ministry of Health uses officially VA to
      reconstruct the history of women who died of cervical cancer. OBJECTIVE: to
      describe the findings of the VA of dead women due to cervical cancer in Tijuana,
      Baja California, Mexico. METHODOLOGY: All death certificates issued in the years
      2001 and 2001 in which cervical cancer was the main cause of death were reviewed.
      The VA included forty-five questions exploring six domains: subjects' personal
      information, sociodemographic characteristics, history of the disease, timely
      medical care, risk factors, affiliation to social security, and information
      registered in the death certificate. RESULTS: Seventy-nine women out of 97 had
      VA. The mean age was 54 years; 33% completed elementary school; 32% had smoking
      history; 50% had more than five pregnancies; 42% started sexual activity before
      the age of 17, 52% had had 2 to 3 sexual partners. 60% had Papanicolau test; 90%
      knew about their condition; 86% received medical care and 34% knew they had
      cancer one year before death. CONCLUSIONS: Verbal autopsy revealed that 40% of
      women who died of cervical cancer did not have Papanicolau test before being
      diagnosed.

PMID- 17550708
TI  - Getting to see the surgeon.

PMID- 17550709
TI  - How evidence-based are CAGS surgeons really?

PMID- 17550710
TI  - Citations and wait-lists: much ado about nothing?

PMID- 17550711
TI  - Positive predictive value of maximal posterior joint-line tenderness in
      diagnosing meniscal pathology: a pilot study.
AB  - OBJECTIVE: The purpose of this prospective study was to determine the positive
      predictive value (PPV) of the point of maximal posterior joint line tenderness
      (JLT), as a clinical sign, to diagnose underlying meniscal tears. METHODS: We
      conducted a prospective study of patients requiring arthroscopic surgery, who
      consecutively presented to the University of Calgary's Sport Medicine Centre. The
      femurotibial joint line was palpated for the point of maximal tenderness. We
      recorded the data on the arthroscopy report. A second examiner (orthopedic sport
      medicine surgical fellow or sport medicine physician) performed the same
      protocol. An arthroscopist documented the site of pathology as detected by
      arthroscopy. RESULTS: We found a PPV of 60.0% and a negative predictive value of
      62.5%, suggesting that maximal posterior JLT may be predictive of meniscal
      pathology. The sensitivity and specificity were 84.6% and 31.2%, respectively (p
      = 0.155), with Fisher's exact test. The kappa score assessed interobserver
      reliability and was good at 0.48. Patients with maximal posterior JLT but no
      meniscal pathology did have other confounding pathology and patients with no
      maximal posterior JLT who had meniscal pathology usually had confounding knee
      pathology. CONCLUSIONS: We found a PPV of 60.0% of maximal posterior JLT and
      meniscal pathology located at the same anatomical site on arthroscopic
      examination.

PMID- 17550712
TI  - The wait for total hip replacement in patients with osteoarthritis.
AB  - OBJECTIVES: We documented the following components of waiting time for total hip
      replacement (THR): first surgical consultation, date of decision to operate and
      date of surgery. We then explored whether these intervals differed by age, sex,
      occupation or quality-of-life score. METHODS: We used a cross-sectional design
      and collected the primary data from patients 2 to 4 weeks before they underwent
      THR. Trained interviewers administered the Medical Outcomes Study Short Form-36
      and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC),
      which included data on event dates, conservative treatment, demographic
      information and quality of life. We illustrated waiting times, quality of life
      and past use of conservative treatment (i.e., cane, exercise, physiotherapy) with
      descriptive statistics (mean [standard deviation] or median [intraquartile
      range]) for continuous variables and with percentages for categorical variables.
      We plotted KaplanMeier graphs for each waiting time component and employed log
      rank analysis to determine whether any of these delays differed by age, sex,
      occupation or disability. We also performed a Cox regression to adjust for all
      covariates simultaneously. RESULTS: The median wait from surgical consultation to
      decision to operate was 0 months. There was no difference between age, sex or
      occupation. The median wait from decision to operate to the date of surgery was 6
      months and did not differ by age, sex or occupation. However, subjects with more
      severe symptoms (WOMAC) underwent surgery earlier than did those with less severe
      disease. CONCLUSION: Although neither of the waiting time components were
      associated with age, sex or occupation, patients with more severe symptoms appear
      to be prioritized for surgery.

PMID- 17550713
TI  - Can community surgeons perform laparoscopic colorectal surgery with outcomes
      similar to tertiary care centres?
AB  - INTRODUCTION: The use of the laparoscopic approach in colorectal surgery (LCS) is
      the subject of active debate. Studies demonstrating its safety and feasibility in
      tertiary care centres are now available. The aim of this study was to examine the
      results of LCS performed in a community hospital setting. METHODS: We
      prospectively studied 100 patients who underwent an LCS at the North Bay District
      Hospital (a 200-bed community hospital located 350 km away from the nearest
      tertiary care centre). All operations were performed by 2 community surgeons who
      transitioned themselves from an open to a laparoscopic approach. RESULTS: Between
      October 2000 and December 2003, 100 patients (56 women and 44 men, mean age 64
      yr) underwent an LCS for benign (n = 54) and malignant (n = 46) disease. Median
      operating time was 165 minutes (range 70350 min), and the conversion rate was
      10%. The intraoperative complication rate was 3%. There were 10 major
      postoperative complications and 14 minor postoperative complications. There was
      no intraoperative mortality and one 30-day mortality secondary to cardiogenic
      shock. The median length of stay was 4.5 days (range 245 d). At a mean follow-up
      of 18 months, no trocar site or wound recurrences were noted. The mean number of
      resected lymphnodes was 10.6. CONCLUSION: Our study suggests that it is possible
      for community surgeons to transition themselves from an open to a laparoscopic
      approach and to perform LCS with outcomes similar to those of tertiary care
      centres.

PMID- 17550714
TI  - Reliability of radiographic measurement of fracture angulation in children with
      femoral shaft fractures.
AB  - INTRODUCTION: Clinical decisions are based on x-ray measures of radiographs.
      However, the reliability of assessing the angular measurement of fractured femurs
      in children is unknown. The purpose of this study was to determine the intra- and
      interrater reliability of an x-ray assessment of femoral shaft fracture
      angulation in children. METHODS: On 2 occasions, 3 raters evaluated 30
      radiographs of children aged 4 to 10 years, 3 to 24 months after a femoral
      fracture. The radiographs were evaluated by an orthopedic surgeon, an orthopedic
      fellow and a research assistant, using a standardized methodology. Reliability
      was assessed with the intraclass correlation coefficient (ICC), an index of
      concordance that ranges from 01, where > 0.75 indicates excellent concordance.
      RESULTS: The ICC for the intrarater ranged from 0.75 to 0.97. The interrater
      reliability ICC for anterior or posterior angulation was 0.91 (95% confidence
      interval [CI] 0.840.95) and for varus or valgus angulation was 0.90 (95% CI
      0.790.95). A change in measurement of more than 5 degrees exceeds the variation
      in measurement and, therefore, can be attributed to a true shift in fracture
      position. CONCLUSIONS: With specific standardized protocols, radiographic
      assessment of femoral fractures is reliable, irrespective of the examiner's level
      of experience.

PMID- 17550715
TI  - Factors associated with citation rates in the orthopedic literature.
AB  - INTRODUCTION: Investigators aim to publish their work in top journals in an
      effort to achieve the greatest possible impact. One measure of impact is the
      number of times a paper is cited after its publication in a journal. We conducted
      a review of the highest impact clinical orthopedic journal (Journal of Bone and
      Joint Surgery, American volume [J Bone Joint Surg Am]) to determine factors
      associated with subsequent citations within 3 years of publication. METHODS: We
      conducted citation counts for all original articles published in J Bone Joint
      Surg Am 2000 (12 issues). We used regression analysis to identify factors
      associated with citation counts. RESULTS: We identified 137 original articles in
      the J Bone Joint Surg Am. There were 749 subsequent citations within 3 years of
      publication of these articles. Study design was the only variable associated with
      subsequent citation rate. Meta-analyses, randomized trials and basic science
      papers received significantly more citations (mean 15.5, 9.3 and 7.6,
      respectively) than did observational studies (mean retrospective 5.3, prospective
      4.2) and case reports (mean 1.5) (p = 0.01). These study designs were also
      significantly more likely to be cited in the general medical literature (p =
      0.02). CONCLUSION: Our results suggest that basic science articles and clinical
      articles with greater methodological safeguards against bias (randomized
      controlled trials and meta-analyses) are cited more frequently than are clinical
      studies with less rigorous study designs (observational studies and case
      reports).

PMID- 17550716
TI  - Influence of local provision of specialty health care service on patient access
      to care.
AB  - INTRODUCTION: The impact of local provision of specialty service on patients'
      access to care was studied in Canada's 13 health care jurisdictions where
      distance may be a barrier limiting access. METHODS: A cross-sectional study of
      routinely collected registry data in Ontario and Nova Scotia was performed. Liver
      transplant was chosen as an indicator service. Transplant rate, disease severity,
      urgency and outcome were studied in adult recipients of first liver transplants
      from 1993 to 2002. Provinces that provided liver transplants were compared with
      those that did not; Ontario regions that provided the service were compared with
      those that did not; and the period of time when liver transplants were available
      in Nova Scotia was compared with the time when they were not. RESULTS: Use varied
      widely between jurisdictions but was consistently higher in provider provinces,
      at 10.9 per million population (pmp) compared with 8.9 pmp in nonprovider
      provinces (p < 0.005). Use was higher in district health councils of Ontario that
      provided transplantation. A larger proportion of patients in provider regions had
      viral or alcoholic etiologies of disease than did those from nonprovider regions,
      who tended to have superior survival after transplant. Service interruption in
      Nova Scotia did not change use rates, with transplant rates remaining above
      average, at 12.0 pmp. CONCLUSIONS: Differences in use between provider and
      nonprovider regions may reflect local service availability as well as local
      patterns of disease and patient referral. Expectations of patients that are
      established by local service availability persist after service is removed.

PMID- 17550717
TI  - Air versus ground transport of major trauma patients to a tertiary trauma centre:
      a province-wide comparison using TRISS analysis.
AB  - OBJECTIVE: The purpose of this study was to compare the outcomes of adult (aged >
      15 yr) blunt trauma patients with an Injury Severity Score (ISS) = 12 who were
      transported to a single tertiary trauma centre (TTC) by helicopter emergency
      medical service (HEMS) versus those transported by ground ambulance. METHODS: We
      retrospectively analyzed all adult (aged > 15 yr) trauma patients between March
      27, 1998 and March 28, 2002 with an ISS score = 12, as identified through the
      provincial trauma registry. We used the Trauma and Injury Severity Score (TRISS)
      methodology to determine a difference in outcomes between the 2 groups. RESULTS:
      We identified 823 patients; of these, we excluded 32 (3.9%) penetrating trauma
      patients. Of the blunt trauma cases (n = 791) 237 (30%) patients were transported
      by air and 554 were transported by ground (70%). A total of 770 (97.3%) patients
      were eligible for TRISS analysis. Using the TRISS methodology, the air group had
      a Z statistic of 2.77, yielding a W score of 6.40. This compared with the ground
      transport group, whose Z statistic was 1.97 and W score was 2.39. CONCLUSION: The
      transport of trauma patients with an ISS = 12 by a provincially dedicated rotor
      wing air medical service was associated with statistically significantly better
      outcomes than those transported by standard ground ambulance. This is the first
      large Canadian study to specifically compare the outcome of patients transported
      by ground with those transported by air.

PMID- 17550718
TI  - Surgical images: musculoskeletal Synchronous multifocal osteosarcoma.

PMID- 17550720
TI  - Pancreatic neuroendocrine tumour presented as isolated gastric varices.

PMID- 17550719
TI  - Adult stem or progenitor cells in treatment for type 1 diabetes: current
      progress.
AB  - Since the development of the Edmonton Islet Transplantation Protocol, islet
      transplantation has given new hope to patients with type 1 diabetes. Like solid
      organ transplantation, one of the biggest challenges islet transplantation faces
      is the shortage of available donor tissue. Finding an alternative source of islet
      tissue has become an increasingly important field of study. The possibility of
      generating insulin-secreting cells and islet tissue with adult pancreatic stem or
      progenitor cells has been investigated extensively. This review aims to discuss
      recent progress in the study of adult pancreatic stem or progenitor cells and to
      suggest future directions in this field.

PMID- 17550721
TI  - [The clinical outcome and complication prevention of thoracoscopic
      instrumentation for adolescent idiopathic scoliosis].

PMID- 17550722
TI  - [One-stage single balloon multiple expansions percutaneous kyphoplasty: report of
      18 cases].
AB  - OBJECTIVE: To observe the effect and safety of one-stage single balloon multiple
      expansions percutaneous kyphoplasty (PKP) in treatment of osteoporotic vertebral
      compressive fracture (OVCF) and spinal tumor. METHODS: One-stage single balloon
      multiple expansions PKP was performed on 18 patients, 5 males and 13 females,
      aged 68.77 (44 - 80), with 45 vertebrae, including 11 case of OVCF (with 29
      diseased vertebrae), 11 cases of multiple vertebral fracture (with 19 diseased
      vertebrae), 5 cases of multiple myeloma (with 12 diseased vertebrae), and 2 case
      of spinal metastatic tumor (with 4 diseased vertebrae), the vital signs were
      record during operation. Pain relief and functional recovery were evaluated with
      visual analogue pain scale (VAS) and Oswestry disability index (ODI) scaling, and
      restoration of vertebral height and Cobb angle were evaluated by X-ray
      examination. Follow-up was conducted by telephone survey or clinic consults for
      12.3 months (6 - 18 months). RESULTS: Operation was successfully performed on all
      patients with an operative time of 29.3 min (55 - 127 min) per vertebra. The
      average pressure of the balloon expansion was 165 Psi (87 - 210 Psi), and the
      average balloon expanded volume was 3.25 ml (1.5 - 4 ml). A balloon was expanded
      2 approximately 5 times in one operation with the average of 2.94 expanded times.
      The bone cement volume injected was 3.95 ml (2 - 8.5 ml) per vertebra. Epidural
      cement leakage was seen in 1 vertebra in 1 case and paraspinal leakage was seen
      in two vertebrae in 1 case. The VAS and ODI scoring of these patients were both
      decreased significantly after operation. Both the anterior height and midline
      height of vertebrae were significantly improved. The pain relief and functional
      recovery were substantial and maintained to the last follow-up without any re
      collapse or adjacent level fracture. CONCLUSION: one-stage single balloon
      multiple expansions PKP is effective, economic and safe in treatment of multi
      level OVCF and spinal tumor.

PMID- 17550723
TI  - [Percutaneous screw fixation of unstable pelvic fracture: experience in 14
      patients].
AB  - OBJECTIVE: To evaluate the clinical feasibility and safety of percutaneous screw
      fixation in the management of vertically unstable pelvic fractures. METHODS:
      Forty S1 CT films of orthopedic patients aged 18 - 73, were analyzed so as to
      provide the best screw entrance point and angle for screw entrance. The data thus
      obtained were used on 14 patients with unequivocally vertical unstable pelvic
      fractures, 11 cases being of Tile C(1) type, 2 of C(2) type, and 1 of C type, 9
      males and 5 females, aged 19 to 68. All the patients received heavy traction to
      reduce displacement before the surgery. Percutaneous pelvic screw fixation of the
      disrupted pelvic ring was performed when the patients were in the supine
      position, and then fixation of sacroiliac joint was performed when the patients
      were in the prone position. RESULTS: S1 CT scanning showed an average distance
      from the standard screw entrance point to the backbone of 10.78 cm (9.80 - 12.00
      cm), and a standard screw entrance angle of 61.24 degrees (52.18 - 68.20
      degrees). Anatomic reduction was achieved in all 14 patients. One patient had
      neurological deficit due to the screw penetrating into 1/2 of the intervertebral
      foramen, but the side-effect was released when the screw was removed 21 days
      after operation. A 6-24 months postoperative follow-up revealed that all the
      patients had recovered from fracture and resumed their previous work. CONCLUSION:
      With advantages including simple procedures, better bony stability, minimal
      invasion of compromised soft tissue and limited blood loss, percutaneous screw
      fixation is a practical technique which can be widely used to treat vertical
      unstable pelvic fracture.

PMID- 17550724
TI  - [The value of arthroscopic techniques in determination of indications of
      unicondylar arthroplasty].
AB  - OBJECTIVE: To discuss the value of arthroscopic techniques in determining the
      indications of unicondylar arthroplasty. METHODS: Twenty-four patients with knee
      osteoarthritis, 14 males and 19 females, aged 63 (49 - 74), who were scheduled to
      undergo unicondylar arthroplasty were arthroscopically evaluated at the beginning
      of surgery. Arthroscopy showed injury of degree IV in the tibial and femoral
      cartilages in the medial compartment, severe abrasion of meniscus, and exposure
      of subchondral bone. Unicondylar arthroplasty was given up on 8 cases because of
      cartilage injuries in the lateral compartment, while the surgery was performed on
      the other 16 cases. All cases underwent synovium debridement, 5 of which
      underwent meniscus repair or partial meniscectomy in the lateral compartment, 4
      underwent patellar reticulum releasing and peri-patellar denervation, 3 cases
      underwent synovium plica resection, and 4 cases had their loose bodies removed.
      Follow-up was conducted on 16 cases for 14 months on average. RESULTS: The
      average Lysholm score of the patients was 67.5 preoperatively and became 94
      postoperatively. After operation, the symptoms of locking and pain were relieved.
      The functional evaluation result was excellent in 12 cases, good in 2, and fair
      in 2. CONCLUSION: Arthroscopic evaluation of intra-articular structures is
      valuable in determination of unicondylar arthroplasty indications. Arthroscopic
      procedures are valuable in minimizing preoperative symptoms.

PMID- 17550726
TI  - [Association between circulating leptin level and anthropometric parameters in
      girls with adolescent idiopathic scoliosis].
AB  - OBJECTIVE: To investigate the correlation between the circulating leptin level
      and the anthropometric parameters and parameters related to pubertal growth, and
      to explore the role of leptin in the abnormal growth pattern in girls with
      adolescent idiopathic scoliosis (AIS). METHODS: One hundred and twenty AIS girls
      selected randomly from the out-patient and in-patient departments, divided into 2
      groups: Group A1 (n = 73, aged 10 - 13) and Group A2 (n = 47, aged 14 - 17), and
      80 14 - 17 year-old healthy girl students receiving physical examination
      underwent measurement of body height and weight. Body mass index (BMI) was
      calculated. Peripheral fasting blood samples were collected to detect the level
      of leptin. The anthropometric data, pubertal status, and circulating leptin level
      were compared between the AIS girls and the controls. The relationships between
      leptin and age, menstrual status, body weight, height, BMI and Risser sign were
      analyzed in the AIS girls. RESULTS: Eighty-eight AIS girls (73%) and 14 healthy
      girls (18%) had a BMI score less than 18.0. The mean leptin level of Group A1 was
      6.2 microg/L, significantly lower than of Group A2 (8.6 microg/L, P = 0.024).
      Compared with the healthy controls, the AIS girls had significantly greater
      corrected height (162.7 cm vs. 160.2 cm, P = 0.026), lower weight (44.3 kg vs.
      53.6 kg, P = 0.01), lower BMI (17.5 kg/m(2) vs. 20.9 kg/m(2), P = 0.01), and
      lower circulating leptin (8.6 microg/L vs. 14.9 microg/L), even after the
      adjustment for age and menstrual status. An inverse correlation was observed
      between the leptin level and the age at menarche (AIS, r = -0.428, P < 0.001;
      controls, r = -0.280, P = 0.013). Whereas, positive correlations were found
      between leptin and age, menstrual status, body weight, height, BMI, and Risser
      sign (r = 0.234 - 0.506, P = 0.01 - < 0.001). CONCLUSION: AIS girls have markedly
      decreased circulating leptin level. Circulating leptin level is associated with
      body weight, BMI, and other growth parameters, suggesting that leptin may play an
      important role in the lower body mass in AIS girls.

PMID- 17550727
TI  - [Selective posterior fusion of single thoracic curve adolescent idiopathic
      scoliosis: experience in 72 cases].
AB  - OBJECTIVE: To prospectively evaluate the strategy of surgery and choice of the
      fusion segments in thoracic adolescent idiopathic scoliosis (AIS) treatment.
      METHODS: Selective posterior fusion was used on 72 AIS patients, 13 male and 59
      female, aged 14.3 (12 - 18), 50 being of Lenke-type IA, 8 Lenke-type IB, and 14
      Lenke-type IC. In principle the upper neutral vertebrae were selected as upper
      instrumented vertebrae. The lower neutral vertebrae, the vertebrae 1 level
      proximal to the neutral vertebrae, or stable vertebrae were chosen as the lower
      instrumented vertebrae based on the analysis of the correlation among the lower
      end vertebrae, neutral vertebrae and stable vertebrae's locations. Standing
      anteroposterior and lateral and side-bending radiographs were taken
      preoperatively, postoperatively and during the follow-up. The coronal and
      sagittal Cobb angle, translation and rotation of apical vertebrae, and trunk
      translation were evaluated to observe the curve correction and trunk balance. The
      patients underwent spinal fusion of 7.3 segments (4 - 10 segments) on average.
      Follow-up was conducted for 15.9 months (12 - 39 months). RESULTS: The thoracic
      curves' coronal Cobb angle before the operation was 56.7 degrees +/- 14.5 degrees
      (40 degrees - 98 degrees), and was 18.5 degrees +/- 8.3 degrees (3 degrees - 40
      degrees) after the operation. The lumbar curves' coronal Cobb angle before
      operation was 33.9 degrees +/- 10.4 degrees (25 degrees - 69 degrees), and was
      11.1 degrees +/- 6.4 degrees (0 degrees - 30 degrees ) after operation. The
      spontaneous correction rate was 66.9% +/- 16% (44% - 100%). The trunk translation
      before operation was 16.1 +/- 10.2 mm (4 - 43 mm), and was 8.2 +/- 6.1 mm (0 - 25
      mm) after operation. Two patients were found with slight trunk decompensation
      postoperatively, but with no progression during a 2-year follow-up. CONCLUSION:
      Determination of the fusion levels based on the analysis of the correlation among
      the end vertebrae, neutral vertebrae and stale vertebrae's location helps obtain
      the satisfying curative effect in the management of single thoracic curve AIS.

PMID- 17550728
TI  - [Anatomical study of human lumbar spine innervation].
AB  - OBJECTIVE: To explore the detailed innervation of the lumbar spine of humans.
      METHODS: Six adult cadavers fixed in a solution containing 10% formalin were
      investigated under a stereomicroscope. The lumbar spine, together with the
      abdominal aorta, inferior vena cava and psoas muscle, was extracted. The
      dissection was focused on various patterns of rami communicantes (RC), including
      superficial oblique rami (SOR) and deep transverse rami (DTR), and their
      relationship to the psoas major muscle, the minute nerve supply of the anterior
      and posterior longitudinal ligaments, vertebral bodies and the intervertebral
      discs. RESULTS: Two types of RC were observed: SOR and DTR. SOR ran obliquely
      between the superficial heads of the psoas major muscle, connecting the
      sympathetic trunk and T12-L2 spinal nerves non-segmentally. DTR, running along
      the lumbar arteries and veins, were distributed segmentally, close to the
      vertebral bodies. On the anterior aspect of the lumbar spine, the anterior
      longitudinal ligaments received branches from the sympathetic trunk and
      splanchnic nerves non-segmentally. On the lateral side of the lumbar spine, the
      vertebral bodies and the intervertebral discs received branches from the DTR and
      ventral rami segmentally, branches from the sympathetic trunk, and, in the upper
      lumbar region, SOR non-segmentally. Within the vertebral canal, the posterior
      aspect of the intervertebral discs and the posterior longitudinal ligaments
      received the sinu-vertebral nerves originating from DTR. CONCLUSION: Exist two
      different types of innervation in the lumbar vertebrae: one originating directly
      from the spinal nerve segmentally, and one reaching the vertebral body and
      intervertebral disc via the sympathetic nerves non-segmentally. Therefore,
      sympathetic nerves are involved in the innervation of the spinal column and
      intervertebral disc and are likely involved in discogenic low back pain.

PMID- 17550729
TI  - [Anatomic study of the supra-infratentorial presigmoid partial labyrinthectomy
      keyhole approach assisted by neuro-navigation].
AB  - OBJECTIVE: To design a new supra-infratentorial presigmoid partial
      labyrinthectomy keyhole approach assisted by neuro-navigation system, and to
      explore the possibility of removing the approach-correlated bone precisely.
      METHODS: Navigation data were established on 8 cadaveric heads fixed by formalin
      and perfused intracranial vessels with colored silicone. Before the operation,
      the important structures were outlined with different colors in the navigation
      system. A 7-cm "C" shape skin incision was performed 1cm behind the helix. On
      elevating the skin flap and musculofascial flap respectively, a 3.5 cm x 3 cm
      bone window was performed. After skeletonized the sigmoid sinus, bony labyrinth
      and the canal for facial nerve assisted by neuro-navigation, the amount of dura
      exposed and the maximal angle of vision were measured before and after partial
      labyrinthectomy with petrous apicectomy, the anatomic structures were observed as
      well. RESULTS: The incision of the supra-infratentorial retrolabyrinthine keyhole
      approach fully met the needs of the presigmoid partial labyrinthectomy keyhole
      approach. The approach-correlated bone could precisely be drilled with the aid of
      neuro-navigation, which could avoid the bewilder in drilling process. This
      approach provided wide exposure to petroclival region, cerebellopontine angle,
      prepontine region and posterior cavernous sinus. After partial labyrinthectomy
      with petrous apicectomy, the horizontal exposure was increased to (18.8 +/- 1.6)
      mm (left side) and (17.7 +/- 1.2) mm (right side); the maximal angle of vision
      was increased to (59.3 +/- 9.2) degrees (left side) and (57.0 +/- 11.0) degrees
      (right side); the vertical exposure increased (10.0 +/- 1.0) mm (left side) and
      (10.0 +/- 0.8) mm (right side); there were significant differences between before
      and after partial labyrinthectomy with petrous apicectomy (P < 0.01). CONCLUSION:
      It is feasible to perform the supra-infratentorial presigmoid partial
      labyrinthectomy keyhole approach. The exposed field and the maximal angle of
      vision can be obviously increased by partial labyrinthectomy with petrous
      apicectomy.

PMID- 17550731
TI  - [Collateral supply in patients with severe carotid stenosis].
AB  - OBJECTIVE: To determine the collateral supply is sufficiency or not in patients
      with carotid stenosis. METHODS: Fifteen consecutive patients with carotid
      stenosis underwent carotid endarterectomy (CEA). We evaluated the patent
      collateral pathways through the anterior and posterior communicating arteries or
      the ophthalmic artery (ACoA; PCoA; OA) with TCD before CEA. A total of 15
      subjects were monitored the mean velocity of the ipsilateral middle cerebral
      artery (mvMCA) by TCD and simultaneously detected stump pressure (SP) after cross
      clamping carotid artery during the operation. RESULTS: Three subjects patent
      anterior communicating artery; 5 cases patent posterior communicating artery; 6
      of 15 patent OA. SP > or = 50 mm Hg in 8 cases and SP < 50 mm Hg in 7 patients
      were detected after cross clamping. The decrease of the ipsilateral mvMCA is less
      than 30% of baseline in 11 cases. Both TCD preoperatively and SP during CEA
      indicated collateral blood adequately or not in 9 cases. Results of 12 patients
      evaluated collateral supply by means of SP and mvMCA changes were common.
      CONCLUSION: TCD is a useful tool for the evaluation of the sufficiency of
      collateral circulation in patients with carotid artery severe stenosis,
      especially monitoring the ipsilateral mvMCA changes during carotid
      endarterectomy.

PMID- 17550732
TI  - [Correlation of cholesterol 24-hydroxylase and ATP-binding cassette transporter
      A1 polymorphisms with Alzheimer's disease].
AB  - OBJECTIVE: To investigate the association of the single nucleotide polymorphisms
      (SNPs) A-->G in the intron 2 of cholesterol 24-hydroxylase (CYP46) gene and G-->A
      (R219K) in the exon 6 of ATP-binding cassette transporter A1 (ABCA1) gene with
      sporadic Alzheimer's disease (SAD) in the Han Chinese population. METHODS:
      Peripheral blood samples were collected from 168 SAD patients, 74 males and 94
      females, aged 74 +/- 8 (52 - 95), with an average age at onset of 69 +/- 7 (47 -
      86), and sex-, and age-matched 215 healthy persons. PCR-restriction fragment
      length polymorphism (PCR-RFLP) was used to detect the genotypes. Apolipoprotein E
      (ApoE) genotyping was conducted. The strength of association between the
      polymorphisms and AD was estimate. RESULTS: The frequency of ApoE genotype of the
      SAD patients was 14%, significantly higher than that of the controls (5.1%,
      chi(2) = 19.060, P < 0.01). The risk of SAD in those with at least one epsilon 4
      allele was 2.8 times that in those without epsilon 4 allele (OR = 2.82, 95% CI =
      1.54 - 5.17, P = 0.001). There was no significant difference in the genotype or
      allele frequencies for CYP46 gene between the SAD patients and controls. However,
      there was an obvious association between the polymorphism of ABCA1 gene and SAD
      (chi(2) = 8.230, P = 0.016). The frequency of G/A + A/A genotypes in the SAD
      patients was 61.3%, significantly lower than that of the controls (73.5%, chi(2)
      = 6.444, P = 0.011). The risk of SAD in the carriers of A alleles (G/A + A/A
      genotypes) was significantly lower than those with GG genotype by 43% (adjusted
      OR = 0.57, 95% CI = 0.36 - 0.91, P = 0.019), and the risk of SAD in the AA
      homozygote carriers was significantly lower than that of the GG genotype carriers
      by 60% (adjusted OR = 0.40; 95% CI = 0.21 - 0.77, P = 0.006). CONCLUSION: The
      CYP46 intron 2 polymorphism may not be associated with the risk of AD, but AA
      genotype or A allele of ABCA1 gene may have a protective effect for AD in Han
      Chinese.

PMID- 17550733
TI  - [Changes of sleep architecture in patients with narcolepsy].
AB  - OBJECTIVE: To investigate the sleep architectures of patients with narcolepsy.
      METHODS: 38 drug-naive narcoleptic patients, 25 males and 13 females, aged 21 +/-
      6.5, and 44 age-, sex ratio-, and BMI-matched normal persons underwent
      polysomnography (PSG) and multiple sleep latency test (MSLT) during one night
      sleep. Conventional visual scoring of the polysomnograms was performed according
      to the international. RESULTS: The sleep latency of the patients was 5.6 min,
      however, 30 patients (79%) complained of fragmented nocturnal sleep and
      difficulty to fall asleep again. The sleep efficiency of the narcoleptics was
      81.7% +/- 12.5%, significantly lower than that of the normal persons (87.1% +/-
      7.9%, P = 0.029). The non-rapid eye movement (NREM) I sleep accounted for (21.5
      +/- 12.2)% in the patients, a proportion significantly higher than that of the
      normal persons [(10.3 +/- 6.3)%, P = 0.000]). The AHI of the patients was 0.6 +/-
      1.3 times/h, not significantly different from that of the normal persons (0.5 +/-
      1.1 times/h). Although the rapid eye movement (REM) period and eye movement
      density of the narcoleptics were significantly increased, their REM period
      duration was not significantly different from that of the normal subjects (17.7%
      +/- 6.9% vs 18.9% +/- 5.5%, P = 0.23), probably due to the interruption of REM
      sleep by more frequent arousals in narcoleptics. PSG did not show significant
      periodic leg movements in these 2 groups. CONCLUSION: One of the important
      symptoms of narcolepsy, night sleep disturbance may contribute to the
      pathological sleepiness of narcolepsy during daytime.

PMID- 17550734
TI  - [Intervertebral disc degeneration model and the rule of migration associated with
      chondrocytes in the nucleus pulposus in rat cervical disc].
AB  - OBJECTIVE: To develop a scientific and reproducible degenerative disc rat model
      for the study on the cervical disc and study the rule of migration associated
      with the chondrocytes in the nucleus pulposus. METHOD: The degenerative cervical
      disc animal model was developed in 40 infancy SD rats by means of forelimb
      amputation. Thirty-six normal rats in the same age served as the control. When
      the rats in the experimental group were 3, 6, 9 and 12 months (named E3, E6, E9
      and E12 group respectively) and in the control group were 4, 8, 12 and 16 months
      (named C4, C8, C12 and C16 group respectively) postoperatively, the vertebral
      columns from C4-5 to C6-7 were removed and observed under radiographic and
      histological examination after the rats were sacrificed. RESULT: Light microscopy
      revealed that aging rat undergoes a chronological transition from a notochordal
      to a fibrocartilaginous NP. The chondrocytes found in mature nucleus pulposus
      originate and migrate from the cartilage endplate. The origin of chondrocytes
      proceeded in a centripetal direction from the periphery toward the center of the
      NP. In the periphery of NP, chondrocytes migrate along collagen fibers; in the
      center part of NP, chondrocytes migrate from endplate to NP in a parallel or
      vertical direction. Overload on the cervical spine elicited by this surgical
      intervention accelerated the process and resulted in cervical intervertebral disc
      degeneration thereafter. CONCLUSION: The availability of this experimental model
      should be valuable for comprehensive understanding of the pathogenesis of
      cervical degeneration. The degeneration process of the bipedal rats'discs is in
      agreement with that of human beings. Chondrocytes in the rat NP originated and
      migrated from the cartilage endplate. There are different rules of the
      chondrocytes migrating from endplate associated with different period of
      degeneration and different region of nucleus pulposus.

PMID- 17550735
TI  - [Growth inhibition of MG-63 cells by cyclin A2 gene-specific small interfering
      RNA].
AB  - OBJECTIVE: To study the impact of small interference RNA (siRNA) targeting cyclin
      A2 gene on the growth of MG-63 and HSF cells and to explore whether cyclin A2
      siRNAs could become a useful tool in the treatment of osteosarcoma. METHODS: One
      pair of siRNA targeting the cyclin A2 mRNA and a pair of nonsense siRNA were
      designed according the current criteria. SiRNA was chemically synthesized and
      purified. The siRNA was transfected into osteosarcoma cell line MG-63 and normal
      human skin fibroblast (HSF) cells via oligofectamine. Cells transfected with
      nonsense siRNA served as the negative control and those only treated with PBS as
      the blank control group. Quantitative fluorescence RT-PCR, Western-blot, MTT
      assay, reverse transcriptase (RT)-PCR, flow cytometry and colony-forming test
      were employed to evaluate the efficacy of RNA interference. At the same time, the
      mRNA expression of PCNA and cyclin B1 in siRNA treated MG-63 cells were examined.
      RESULTS: 1 nmol/L, 10 nmol/L, 50 nmol/L and 100 nmol/L cyclin A2-siRNA can
      reduced cyclin A2 mRNA and protein expression respectively by 9.43%, 56.35%,
      79.17% and 84.30% as compared with that of the blank control group, whereas the
      negative and blank control groups had similar expression levels. After 48 h
      treatment with 10 nmol/L siRNA, MG-63 cells were arrested in G0/G1 phase and the
      proliferation of this tumor cell was suppressed by 39.06% 48 h after
      transfection. Furthermore, the treated MG-63 cells showed less colony-forming
      ability. Increasing the siRNA concentration to 50 nmol/L can further inhibit the
      proliferation of MG-63 cells by 54.94%. In addition, the cyclin A2-depleted MG-63
      cells showed decreased levels of PCNA and cyclin B1. In contrast, although cyclin
      A2 mRNA and protein expression in HSF reduced 58.13% 48 h after treatment by 50
      nmol/L siRNA, these cells exhibited only a slight change in cell cycle, and no
      clear inhibition of proliferation and impaired plate colony-forming ability was
      observed. CONCLUSION: Cyclin A2 gene maybe served as a potential target for tumor
      therapy. RNA interference induces obvious inhibition of cyclin A2 mRNA and
      protein expression in MG-63 and HSF cells, which consequently downregulate the
      proliferation of MG-63 cells. There is few inhibitory effect on the proliferation
      by siRNAs for HSF cells. These results indicate that siRNAs against cyclin A2
      could become a potential antiproliferative tool in future antitumor therapy.

PMID- 17550736
TI  - [The low molecular weight heparin on rat pulmonary surfactant associated protein
      A of acute pulmonary embolism].
AB  - OBJECTIVE: To explore the effect of low molecular weight heparin (LMWH) on the
      changes of pulmonary surfactant associated protein A (SPA) of rats in acute
      pulmonary embolism. METHODS: Male SD rats were injected with medical gelfoam
      microspheres via jugular vein to induce PE model. Rats were randomized into three
      groups: control group (n = 8), embolism for 2 weeks group (n = 8) and LMWH
      therapy group (n = 8); The LMWH therapy group were injected Nadroparin
      subcutaneously immediately after operation, 0.1 ml/10 kg, once every 12 h. Saline
      were injected into the control group instead of gelfoam granule solution without
      further procedure. All the rats were sacrificed at the time of 2 weeks. Pulmonary
      artery pressure were detected by right heart catheterization and artery blood gas
      were analyzed at the time of sacrifice. Lung tissue were sliced and dyed with HE
      to observe the embolism of pulmonary artery. Methods of RT-PCR and western blot
      were used to study the changes of SPA mRNA and SPA protein in lung tissue.
      RESULTS: In control group, embolism group and LMWH group, the pulmonary pressure
      were (14.2 +/- 4.1) mm Hg, (29.0 +/- 8.2) mm Hg, (25.50 +/- 2.74) mm Hg
      respectively (F3.01, P < 0.05); the artery oxygen blood pressure (PaO2) were
      (94.1 +/- 8.8) mm Hg, (73.4 +/- 14.3) mm Hg, (82.86 +/- 3.73) mm Hg respectively
      (F 1.31, P < 0.05); SPA mRNA in three groups were 1.43 +/- 0.51, 0.87 +/- 0.35,
      1.07 +/- 0.20 respectively (F 2.87, P < 0.05); and SPA protein were 1.00 +/-
      0.00, 0.52 +/- 0.32, 0.90 +/- 0.22 respectively (F 2.96, P < 0.05); Under
      microscope, lung tissue were seen congestion, edema, infiltration of inflammatory
      cells in embolism group, which were lessened in LMWH group. CONCLUSIONS: The lung
      SPA decrease significantly in acute pulmonary embolism, and LMWH can increase the
      SPA, which may be one of mechanisms of LMWH in treatment of pulmonary embolism.

PMID- 17550737
TI  - [Study on the activities' alteration of the proteasome in neurons of cortex and
      its relation with delayed neuron death after reperfusion following ischemia].
AB  - OBJECTIVE: To investigate the activities' alteration of the proteasome in neurons
      of cortex and its relation with delayed neuron death after reperfusion following
      ischemia. METHODS: 20 minutes transient global ischemia rat model was used.
      Following different reperfusion period, all the 50 rats were divided into 5
      groups, sham-operation group, 0.5 hour recovery group, 4 hours recovery group, 24
      hours recovery group and 72 hours recovery group, 10 rats each group. Suc-llvy
      amc was used as substrate for measuring proteasome's activities. Delayed neuron
      death after reperfusion following ischemia was observed under light microscope by
      HE staining. Proteasome's distribution was observed under laser scanning confocal
      microscope after immuno-histo-chemical staining. RESULTS: The proteasome activity
      of sham group was 54 602 +/- 1602, and that of 0.5 h reperfusion following
      ischemia was 42,036 +/- 1465 (compared with sham group, P < 0.01). Although the
      proteasome activity temporarily recovered to 47,536 +/- 2532 (P < 0.05) after 4 h
      reperfusion, it still decreased to 45,450 +/- 649 (P < 0.01) after 24 h
      reperfusion, and to 43,108 +/- 995 (P < 0.01) after 72 h reperfusion. HE staining
      showed that parts of neurons in the cortex died after 72 hours reperfusion. Under
      laser scanning microscope, we could observe that after 24 hours reperfusion,
      proteasome in both nucleus and cytoplasma significantly decreased; after 72 hours
      reperfusion, proteasome almost disappeared totally in nucleus and only a small
      part of proteasome still existed in cytoplasm. CONCLUSIONS: Decreasing of the
      proteasome's activities is an important factor for delayed neuron death after
      reperfusion following ischemia.

PMID- 17550742
TI  - Colonic preparation for computed tomographic colonography: understanding the
      relative advantages and disadvantages of a noncathartic approach.

PMID- 17550743
TI  - Colonoscopy: the dominant and preferred colorectal cancer screening strategy in
      the United States.

PMID- 17550744
TI  - Prevention of catheter-related bloodstream infections: looking to the department
      of veterans affairs health care system for guidance.

PMID- 17550745
TI  - Assessing attitudes toward laxative preparation in colorectal cancer screening
      and effects on future testing: potential receptivity to computed tomographic
      colonography.
AB  - OBJECTIVE: To investigate whether removal of the laxative preparation would
      improve colorectal cancer (CRC) screening rates. RESPONDENTS AND METHODS: Data
      are from a mixed-mode mail and telephone survey of 1636 noninstitutionalized
      Minnesota residents who were 18 years or older that was conducted from July 15
      through October 25, 2005. The overall response rate was 49%. Analysis focused on
      the 759 respondents who were 50 years or older. RESULTS: One third (32%) of the
      respondents identified the laxative preparation as the most troublesome part of
      CRC screening. Overall, the self-reported likelihood and anticipated timing of
      examination increase when the laxative preparation is removed. Both univariate
      and multivariate analysis showed that the odds of being "much more likely" to
      undergo screening in the future with a test that does not include a laxative
      preparation are greatest among those who have been tested previously, regard the
      laxative preparation as a big problem, or both. CONCLUSION: In this prospective
      survey, laxative preparation appeared to be a major disincentive to CRC
      screening. Emerging data suggest that performance of laxative-free computed
      tomographic colonography may represent an attractive option that removes this
      relatively common disincentive to CRC screening participation.

PMID- 17550746
TI  - Use of central venous catheter-related bloodstream infection prevention practices
      by US hospitals.
AB  - OBJECTIVE: To examine the extent to which US acute care hospitals have adopted
      recommended practices to prevent central venous catheter-related bloodstream
      infections (CR-BSIs). PARTICIPANTS AND METHODS: Between March 16, 2005, and
      August 1, 2005, a survey of infection control coordinators was conducted at a
      national random sample of nonfederal hospitals with an intensive care unit and
      more than 50 hospital beds (n=600) and at all Department of Veterans Affairs (VA)
      medical centers (n=119). Primary outcomes were regular use of 5 specific
      practices and a composite approach for preventing CR-BSIs. RESULTS: The overall
      survey response rate was 72% (n=516). A higher percentage of VA compared to non
      VA hospitals reported using maximal sterile barrier precautions (84% vs 71%;
      P=.01); chlorhexidine gluconate for insertion site antisepsis (91% vs 69%;
      P<.001); and a composite approach (62% vs 44%; P=.003) combining concurrent use
      of maximal sterile barrier precautions, chlorhexidine gluconate, and avoidance of
      routine central line changes. Those hospitals having a higher safety culture
      score, having a certified infection control professional, and participating in an
      infection prevention collaborative were more likely to use CR-BSI prevention
      practices. CONCLUSION: Most US hospitals are using maximal sterile barrier
      precautions and chlorhexidine gluconate, 2 of the most strongly recommended
      practices to prevent CR-BSIs. However, fewer than half of non-VA US hospitals
      reported concurrent use of maximal sterile barrier precautions, chlorhexidine
      gluconate, and avoidance of routine central line changes. Wider use of CR-BSI
      prevention practices by hospitals could be encouraged by fostering a culture of
      safety, participating in infection prevention collaboratives, and promoting
      infection control professional certification.

PMID- 17550747
TI  - Relationship between low bone mineral density and exercise-induced myocardial
      ischemia.
AB  - OBJECTIVE: To evaluate the relationship between bone mineral density (BMD) and
      ischemic heart disease and exercise capacity, as assessed by stress testing.
      PATIENTS AND METHODS: We retrospectively reviewed entries in the echocardiography
      database for 28,048 consecutive patients who underwent exercise echocardiography
      for standard clinical indications between August 1, 1998, and October 1, 2003, to
      determine which of these patients had also undergone dual-energy x-ray
      absorptiometry to measure femoral neck BMD before the procedure. Of the 1194
      patients meeting both criteria, 28 were excluded because of missing data and 24
      because they were tested with an exercise protocol other than the Bruce protocol,
      leaving 1142 patients to be included. RESULTS: Of the included study patients,
      643 (56%) had a T score of -1.0 or less (mean age +/- SD, 67 +/- 0 years; 87%
      women), and 499 (44%) had a T score greater than -1.0 (60 +/- 10 years; 90%
      women). For every 1-unit decrease in femoral neck T score, a 0.23 minute decrease
      in treadmill exercise duration was observed, once values had been adjusted for
      age and other patient characteristics (95% confidence interval [CI], 0.11-0.35;
      P<.001). Furthermore, for every 1-unit decrease in T score, there was a 22%
      increased risk of myocardial ischemia after adjustments (hazard ratio, 1.22; 95%
      CI, 1.06-1.41; P=.004). Overall, after adjustments, patients with a BMD of -1.0
      or less who were referred for exercise echocardiography had a 43% greater risk of
      myocardial ischemia than did patients referred with normal BMD (hazard ratio,
      1.43; 95% CI, 1.06-1.94; P=.02). CONCLUSIONS: Lower BMD is associated with
      myocardial ischemia and decreased exercise capacity during exercise
      echocardiography. Persons with low BMD who present with symptoms suggestive of
      cardiovascular disease are more likely to have myocardial ischemia than are those
      with normal BMD.

PMID- 17550748
TI  - Report of 255 clinical ethics consultations and review of the literature.
AB  - OBJECTIVE: To review clinical ethics consultations at a tertiary care academic
      medical center. METHODS: We retrospectively reviewed all ethics consultations
      (and associated patient medical records) conducted at the Mayo Clinic in
      Rochester, Minn, between April 6, 1995, and December 31, 2005. RESULTS: Of the
      255 consultations, 101 (40%) reviewed intensive care unit care, 103 (40%)
      involved patients who died during hospitalization, and 174 (68%) were requested
      by physicians. The most common primary diagnoses of the patients involved were
      malignancy (18%, n=47), neurologic disease (18%, n=47), and cardiovascular
      disease (17%, n=43). Most cases involved multiple issues: patient competency and
      decision-making capacity (82%, n=208), staff member disagreement with care plans
      (76%, n=195), end-of-life and quality-of-life issues (60%, n=154), and goals of
      care and futility (54%, n=138). Withholding or withdrawing measures was the focus
      of 132 (52%) of the consultations. We also identified previously published
      reports of ethics consultations and compared the findings of those reports with
      ours. CONCLUSIONS: Despite advances in medicine, the nature of ethical dilemmas
      remains relatively unchanged. Issues of communication, family conflict, and
      futility continue to give rise to ethical quandaries.

PMID- 17550749
TI  - Treatment of benign orbital pseudolymphomas with the monoclonal anti-CD20
      antibody rituximab.
AB  - OBJECTIVE: To report the results of treating patients with orbital
      pseudolymphomas with the anti-CD20 monoclonal antibody rituximab. PATIENTS AND
      METHODS: Patients were included in the study if they had an orbital mass and
      biopsy-proven orbital pseudolymphomas between January 1, 1998, and December 31,
      2005. The study focused on patients treated with rituximab. RESULTS: Ninety-eight
      patients were evaluated, and the biopsy results revealed malignant non-Hodgkin
      lymphoma in 72 (73%); the other 26 (27%) had a pseudolymphoma. Eleven (42%) of
      the 26 patients with a pseudolymphoma were treated with rituximab, 375 mg/m2,
      intravenously each week for 4 doses, and 10 (91%) of the 11 responded. Seven
      patients were either treated with maintenance rituximab or successfully retreated
      with rituximab after relapse. None of the 10 responders has become refractory to
      rituximab. CONCLUSION: Benign lymphoproliferative tumors are responsive to
      monoclonal antibody therapy targeted to B lymphocytes. Rituximab should be
      considered a treatment option for orbital pseudolymphomas.

PMID- 17550750
TI  - Bedside estimation of risk from percutaneous coronary intervention: the new Mayo
      Clinic risk scores.
AB  - OBJECTIVE: To derive risk models for percutaneous coronary intervention (PCI)
      outcomes from clinical and laboratory variables available before the procedure so
      they can be used for preprocedure risk stratification. PATIENTS AND METHODS:
      Using the Mayo Clinic registry, we analyzed 9035 PCIs on 7640 unique patients
      from January 1, 2000, through April 30, 2005. We included only the first PCI per
      patient (n=7457). Logistic regression was used to model the calculated risk score
      and major procedural complications. Separate risk models were made for mortality
      and major adverse cardiovascular events (MACE) derived solely from baseline and
      laboratory characteristics. Final risk scores for procedural death, defined as
      any death during the index hospitalization, and MACE contained the same 7
      variables (age, myocardial infarction less than or equal to 24 hours,
      preprocedural shock, serum creatinine level, left ventricular ejection fraction,
      congestive heart failure, and peripheral artery disease). RESULTS: Models had
      adequate goodness of fit, and areas under the receiver operating characteristic
      curve were 0.74 and 0.89 for MACE and procedural death, respectively, indicating
      excellent overall discrimination. The model was robust across many subgroups,
      including those undergoing elective PCI, those having diabetes mellitus, and
      elderly patients. Bootstrap analysis indicated that the model was not overfit to
      the available data set. CONCLUSION: Before coronary angiography is performed, a
      risk-scoring system based on 7 variables can be used conveniently to predict
      cardiovascular complications after PCI. This model may be useful for providing
      patients with individualized, evidence-based estimates of procedural risk as part
      of the informed consent process.

PMID- 17550751
TI  - Association of novel risk factors with the ankle brachial index in African
      American and non-Hispanic white populations.
AB  - OBJECTIVES: To investigate whether novel risk factors, including C-reactive
      protein (CRP), fibrinogen, lipoprotein(a) [Lp(a)], and homocysteine levels, are
      associated with the ankle brachial index (ABI) in African American and non
      Hispanic white populations and whether novel risk factors account for ethnic
      differences in peripheral arterial disease (PAD). PARTICIPANTS AND METHODS:
      Between December 2000 and October 2004, original participants in the Genetic
      Epidemiology Network of Arteriopathy study returned for a second study visit to
      undergo measurement of risk factors and ABI. The CRP, Lp(a), and homocysteine
      levels were log transformed to reduce skewness. Multivariable regression analyses
      were used to assess whether a novel risk factor was associated with ABI after
      adjustment for conventional risk factors and whether ethnicity was associated
      with PAD (ABI, <or=0.95) after adjustment for conventional and novel risk
      factors. RESULTS: Of 2229 study participants, the ABI was determined in 1395
      African American participants (mean +/- SD age, 63 +/- 9 years; 71% women) and
      834 white participants (mean +/- SD age, 58 +/- 9 years; 62% women) who belonged
      to hypertensive sibships. The mean ABI was lower in African American than in
      white individuals (0.99 +/- 0.1 vs 1.13 +/- 0.1; P < .001). In both ethnic
      groups, higher levels of CRP, fibrinogen, and homocysteine were each associated
      with a lower ABI after adjustment for conventional risk factors. In African
      American participants, the Lp(a) level was also significantly associated with the
      ABI. African American ethnicity was associated with the presence of PAD after
      adjustment for conventional risk factors (men: odds ratio [OR], 3.04; 95%
      confidence interval [CI], 1.80-5.15; women: OR, 2.82; 95% CI, 1.85-4.29), but the
      risk was significantly attenuated after additional adjustment for novel risk
      factors (men: OR, 2.11; 95% CI, 1.21-3.70; women: OR, 1.98; 95% CI, 1.26-3.11).
      CONCLUSION: Novel risk factors are associated with interindividual variation in
      ABI in African American and non-Hispanic white populations and partly account for
      the increased risk of PAD associated with African American ethnicity.

PMID- 17550752
TI  - Fluoride-related bone disease associated with habitual tea consumption.
AB  - Acquired osteosclerosis is a rare disorder of bone formation but an important
      consideration in adults with sclerotic bones or elevated bone density results. In
      such patients, malignancy, hepatitis C, and fluorosis should all be considered
      when making a diagnosis. We describe 4 patients evaluated at our Metabolic Bone
      Disease Clinic from May 1, 1997, to July 1, 2006, whose bone disorders resulted
      from chronic fluoride exposure due to excessive tea intake. Three of these
      patients had toxic serum fluoride levels (> 15 micromol/L). Although the clinical
      presentation of the patients varied, all 4 had an unexpectedly elevated spine
      bone mineral density that was proportionately higher than the bone mineral
      density at the hip. Other clinical features included gastrointestinal symptoms
      such as nausea, vomiting, and weight loss; lower extremity pain sometimes
      associated with stress fractures of the lower extremities; renal insufficiency;
      and elevated alkaline phosphatase levels. Readily available, tea often contains
      high levels of fluoride. Obsessive-compulsive drinking behaviors and renal
      insufficiency may predispose to excessive fluoride consumption and accumulation.
      The current cases show that fluoride-related bone disease is an important
      clinical consideration in patients with dense bones or gastrointestinal symptoms
      and a history of excessive tea consumption. Furthermore, fluoride excess should
      be considered in all patients with a history of excessive tea consumption,
      especially due to its insidious nature and nonspecific clinical presentation.

PMID- 17550753
TI  - Reading the tea leaves: anticarcinogenic properties of (-)-epigallocatechin-3
      gallate.
AB  - Green tea is an extremely popular beverage worldwide. Derivatives of green tea,
      particularly (-)-epigallocatechin-3-gallate (EGCG), have been proposed to have
      anticarcinogenic properties based on preclinical, observational, and clinical
      trial data. To summarize, clarify, and extend current knowledge, we conducted a
      comprehensive search of the PubMed database and other secondary data sources, as
      appropriate, regarding the chemopreventive potential of EGCG. Apparently, EGCG
      functions as an antioxidant, preventing oxidative damage in healthy cells, but
      also as an antiangiogenic agent, preventing tumors from developing a blood supply
      needed to grow larger. Furthermore, EGCG may stimulate apoptosis in cancerous
      cells by negatively regulating the cell cycle to prevent continued division.
      Finally, EGCG exhibits antibacterial activity, which may be implicated in the
      prevention of gastric cancer. Although in vitro research of the anticarcinogenic
      properties of EGCG seems promising, many diverse and unknown factors may
      influence its in vivo activity in animal and human models. Some epidemiological
      studies suggest that green tea compounds could protect against cancer, but
      existing data are inconsistent, and limitations in study design hinder full
      interpretation and generalizability of the published observational findings.
      Several clinical trials with green tea derivatives are ongoing, and further
      research should help to clarify the clinical potential of EGCG for
      chemoprevention and/or chemotherapy applications.

PMID- 17550754
TI  - Basics of quality improvement in health care.
AB  - With the rapid expansion of knowledge and technology and a health care system
      that performs far below acceptable levels for ensuring patient safety and needs,
      front-line health care professionals must understand the basics of quality
      improvement methodologies and terminology. The goals of this review are to
      provide clinicians with sufficient information to understand the fundamentals of
      quality improvement, provide a starting point for improvement projects, and
      stimulate further inquiry into the quality improvement methodologies currently
      being used in health care. Key quality improvement concepts and methodologies,
      including plan-do-study-act, six-sigma, and lean strategies, are discussed, and
      the differences between quality improvement and quality-of-care research are
      explored.

PMID- 17550755
TI  - 56-Year-old man with rash, abdominal pain, and arthralgias.

PMID- 17550756
TI  - Current management strategies for ovarian cancer.
AB  - Epithelial ovarian cancer originates in the layer of cells that covers the
      surface of the ovaries. The disease spreads readily throughout the peritoneal
      cavity and to the lymphatics, often before causing symptoms. Of the cancers
      unique to women, ovarian cancer has the highest mortality rate. Most women are
      diagnosed as having advanced stage disease, and efforts to develop new screening
      approaches for ovarian cancer are a high priority. Optimal treatment of ovarian
      cancer begins with optimal cytoreductive surgery followed by combination
      chemotherapy. Ovarian cancer, even in advanced stages, is sensitive to a variety
      of chemotherapeutics. Although improved chemotherapy has increased 5-year
      survival rates, overall survival gains have been limited because of our inability
      to eradicate all disease. Technologic advances that allow us to examine the
      molecular machinery that drives ovarian cancer cells have helped to identify
      numerous therapeutic targets within these cells. In this review, we provide an
      overview of ovarian cancer with particular emphasis on recent advances in
      operative management and systemic therapies.

PMID- 17550757
TI  - Temozolomide-associated organizing pneumonitis.
AB  - Temozolomide is an oral alkylating agent recently approved for the treatment of
      glioblastoma multiforme. It has a favorable side effect profile and is generally
      well tolerated. Although mild respiratory symptoms have been described, pulmonary
      toxicity that requires discontinuation of therapy is rare. To our knowledge, this
      is the first case of temozolomide-associated organizing pneumonitis.

PMID- 17550758
TI  - On learning to write.

PMID- 17550759
TI  - RecA.

PMID- 17550760
TI  - Marr's vision: twenty-five years on.
AB  - It is twenty-five years since the posthumous publication of David Marr's book
      Vision[1]. Only 35 years old when he died, Marr had already dramatically
      influenced vision research. His book, and the series of papers that preceded it,
      have had a lasting impact on the way that researchers approach human and computer
      vision.

PMID- 17550761
TI  - Cephalopod dynamic camouflage.

PMID- 17550762
TI  - Temporal freezing of visual features.

PMID- 17550763
TI  - Temporal coordination signals coalition quality.

PMID- 17550764
TI  - Endosymbiosis: the evil within.
AB  - A recent study has revealed a novel feature of the symbiosis between a bacterium
      and a fungal pathogen. In addition to producing a pathogenic toxin, the
      endosymbiont of the rice pathogen Rhizopus microsporus controls the ability of
      the fungus to form sporangia and spores.

PMID- 17550765
TI  - Systems biology: a switch for sex.
AB  - The yeast pheromone response pathway works in a graded fashion, such that more
      pheromone leads to more response, but a recent study has shown that small
      modifications convert it into a bistable switch, with implications for the
      evolution and engineering of reaction networks.

PMID- 17550766
TI  - Visual neuroscience: hypercomplex cells in the arthropod visual system.
AB  - Newly described visual interneurons in flies have sophisticated receptive field
      properties reminiscent of neurons in the mammalian visual cortex. The cells are
      well-suited to compute motion of conspecific females that male flies aerially
      intercept.

PMID- 17550767
TI  - Building ribosomes: even more expensive than expected?
AB  - Recent quantitative analyses of ribosomal protein trafficking in HeLa cells have
      revealed a prominent and unexpected role for the proteasome in regulating the
      availability of ribosomal proteins for subunit assembly.

PMID- 17550768
TI  - Delayed dispersal: youth costs carry lifetime gains.
AB  - An analysis of reproductive success in the green woodhoopoe Phoeniculus purpures
      challenges the view that delayed dispersal is costly. Females delaying dispersal
      for longer had more reproductive events in life and higher lifetime production of
      offspring.

PMID- 17550769
TI  - Mental time travel: animals anticipate the future.
AB  - Recent behavioral experiments with scrub jays and nonhuman primates indicate they
      can anticipate and plan for future needs not currently experienced. Combined with
      accumulating evidence for episodic-like memory in animals, these studies suggest
      that some animals can mentally time travel into both the past and future.

PMID- 17550770
TI  - Speech perception: linking comprehension across a cortical network.
AB  - Listening to speech amidst noise is facilitated by a variety of cues, including
      the predictable use of certain words in certain contexts. A recent fMRI study of
      the interaction between noise and semantic predictability has identified a
      cortical network involved in speech comprehension.

PMID- 17550771
TI  - Behavioural ecology: niche construction via grooming and extortion?
AB  - A recent study shows that brood parasitic cowbirds employ Mafia-like tactics to
      discourage rejection of their broods by a common host. This may be a new example
      of animals adaptively 'constructing' key features of their ecological niches.

PMID- 17550772
TI  - Heterochronic genes and the nature of developmental time.
AB  - Timing is a fundamental issue in development, with a range of implications from
      birth defects to evolution. In the roundworm Caenorhabditis elegans, the
      heterochronic genes encode components of a molecular developmental timing
      mechanism. This mechanism functions in diverse cell types throughout the animal
      to specify cell fates at each larval stage. MicroRNAs play an important role in
      this mechanism by stage-specifically repressing cell-fate regulators. Recent
      studies reveal the surprising complexity surrounding this regulation--for
      example, a positive feedback loop may make the regulation more robust, and
      certain components of the mechanism are expressed in brief periods at each stage.
      Other factors reveal the potential for important roles of steroid hormones and
      targeted proteolysis. Investigation of the heterochronic genes has revealed a
      mechanism composed of precisely timed switches linked to discrete developmental
      stages. Timing is a dimension of developmental regulation that may be difficult
      to witness in vertebrates because developmental stages are not as discrete as in
      C. elegans, each tissue is likely to be independently regulated. Homologs of
      certain heterochronic genes of vertebrates show temporally regulated expression
      patterns, and may ultimately reveal timing mechanisms not previously known to
      exist.

PMID- 17550773
TI  - FGF21: a missing link in the biology of fasting.
AB  - A sufficient energy supply is essential for life; consequently, multiple
      mechanisms have evolved to ensure both energy availability and conservation
      during fasting and starvation. Two reports in this issue of Cell Metabolism
      (Badman et al., 2007; Inagaki et al., 2007) demonstrate that FGF21, a circulating
      protein produced in the liver in response to the PPARalpha transcription factor,
      is a "missing link" in the biology of fasting, inducing adipose tissue lipolysis,
      liver ketogenesis, and metabolic adaptation to the fasting state.

PMID- 17550774
TI  - Live longer through PHAsting.
AB  - Dietary restriction provides considerable health benefits and may even increase
      life span in humans. Panowski et al. (2007) have now identified PHA-4/FoxA as an
      essential and specific component of DR-induced life-span extension in C. elegans.

PMID- 17550775
TI  - Osteocyte messages from a bony tomb.
AB  - Until recently, osteocytes have escaped the limelight, embedded within their cave
      like lacunae in the mineralized matrix of bone. In this issue of Cell Metabolism,
      Tatsumi et al. (2007) present evidence that this "third bone cell" can send
      either inhibitory signals to osteoclasts to maintain bone mass with normal
      loading or stimulatory signals to osteoclasts to initiate bone loss upon
      immobilization, thereby playing an indispensable role in skeletal homeostasis.

PMID- 17550776
TI  - TXNIP links redox circuitry to glucose control.
AB  - Thioredoxin-interacting protein (TXNIP) binds and inhibits the reducing activity
      of thioredoxin. A new study (Parikh et al., 2007) implicates this redox rheostat
      as a negative regulator of peripheral glucose metabolism in humans. Investigators
      combined human physiology, genomic screening, and cell-based genetic studies to
      highlight TNXIP as a potential culprit in the pathogenesis of type 2 diabetes.

PMID- 17550777
TI  - Endocrine regulation of the fasting response by PPARalpha-mediated induction of
      fibroblast growth factor 21.
AB  - Peroxisome proliferator-activated receptor alpha (PPARalpha) regulates the
      utilization of fat as an energy source during starvation and is the molecular
      target for the fibrate dyslipidemia drugs. Here, we identify the endocrine
      hormone fibroblast growth factor 21 (FGF21) as a mediator of the pleiotropic
      actions of PPARalpha. FGF21 is induced directly by PPARalpha in liver in response
      to fasting and PPARalpha agonists. FGF21 in turn stimulates lipolysis in white
      adipose tissue and ketogenesis in liver. FGF21 also reduces physical activity and
      promotes torpor, a short-term hibernation-like state of regulated hypothermia
      that conserves energy. These findings demonstrate an unexpected role for the
      PPARalpha-FGF21 endocrine signaling pathway in regulating diverse metabolic and
      behavioral aspects of the adaptive response to starvation.

PMID- 17550778
TI  - Hepatic fibroblast growth factor 21 is regulated by PPARalpha and is a key
      mediator of hepatic lipid metabolism in ketotic states.
AB  - Mice fed a high-fat, low-carbohydrate ketogenic diet (KD) exhibit marked changes
      in hepatic metabolism and energy homeostasis. Here, we identify liver-derived
      fibroblast growth factor 21 (FGF21) as an endocrine regulator of the ketotic
      state. Hepatic expression and circulating levels of FGF21 are induced by both KD
      and fasting, are rapidly suppressed by refeeding, and are in large part
      downstream of PPARalpha. Importantly, adenoviral knockdown of hepatic FGF21 in KD
      fed mice causes fatty liver, lipemia, and reduced serum ketones, due at least in
      part to altered expression of key genes governing lipid and ketone metabolism.
      Hence, induction of FGF21 in liver is required for the normal activation of
      hepatic lipid oxidation, triglyceride clearance, and ketogenesis induced by KD.
      These findings identify hepatic FGF21 as a critical regulator of lipid
      homeostasis and identify a physiological role for this hepatic hormone.

PMID- 17550779
TI  - Insulin action in AgRP-expressing neurons is required for suppression of hepatic
      glucose production.
AB  - Insulin action in the central nervous system regulates energy homeostasis and
      glucose metabolism. To define the insulin-responsive neurons that mediate these
      effects, we generated mice with selective inactivation of the insulin receptor
      (IR) in either pro-opiomelanocortin (POMC)- or agouti-related peptide (AgRP)
      expressing neurons of the arcuate nucleus of the hypothalamus. While neither POMC
      nor AgRP-restricted IR knockout mice exhibited altered energy homeostasis,
      insulin failed to normally suppress hepatic glucose production during euglycemic
      hyperinsulinemic clamps in AgRP-IR knockout (IR(DeltaAgRP)) mice. These mice also
      exhibited reduced insulin-stimulated hepatic interleukin-6 expression and
      increased hepatic expression of glucose-6-phosphatase. These results directly
      demonstrate that insulin action in POMC and AgRP cells is not required for steady
      state regulation of food intake and body weight. However, insulin action
      specifically in AgRP-expressing neurons does play a critical role in controlling
      hepatic glucose production and may provide a target for the treatment of insulin
      resistance in type 2 diabetes.

PMID- 17550780
TI  - A role for brain-specific homeobox factor Bsx in the control of hyperphagia and
      locomotory behavior.
AB  - Food intake and activity-induced thermogenesis are important components of energy
      balance regulation. The molecular mechanism underlying the coordination of food
      intake with locomotory behavior to maintain energy homeostasis is unclear. We
      report that the brain-specific homeobox transcription factor Bsx is required for
      locomotory behavior, hyperphagia, and expression of the hypothalamic
      neuropeptides Npy and Agrp, which regulate feeding behavior and body weight. Mice
      lacking Bsx exhibit reduced locomotor activity and lower expression of Npy and
      Agrp. They also exhibit attenuated physiological responses to fasting, including
      reduced increase of Npy/Agrp expression, lack of food-seeking behavior, and
      reduced rebound hyperphagia. Furthermore, Bsx gene disruption rescues the obese
      phenotype of leptin-deficient ob/ob mice by reducing their hyperphagia without
      increasing their locomotor activity. Thus, Bsx represents an essential factor for
      NPY/AgRP neuronal function and locomotory behavior in the control of energy
      balance.

PMID- 17550781
TI  - Targeted ablation of osteocytes induces osteoporosis with defective
      mechanotransduction.
AB  - Bone remodeling is performed by osteoclasts and osteoblasts at the bone surface.
      Inside of bone is a network of numerous osteocytes, whose specific function has
      remained an enigma. Here we describe a transgenic mouse model in which inducible
      and specific ablation of osteocytes is achieved in vivo through targeted
      expression of diphtheria toxin (DT) receptor. Following a single injection of DT,
      approximately 70%-80% of the osteocytes, but apparently no osteoblasts, were
      killed. Osteocyte-ablated mice exhibited fragile bone with intracortical porosity
      and microfractures, osteoblastic dysfunction, and trabecular bone loss with
      microstructural deterioration and adipose tissue proliferation in the marrow
      space, all of which are hallmarks of the aging skeleton. Strikingly, these
      "osteocyte-less" mice were resistant to unloading-induced bone loss, providing
      evidence for the role of osteocytes in mechanotransduction. Thus, osteocytes
      represent an attractive target for the development of diagnostics and
      therapeutics for bone diseases, such as osteoporosis.

PMID- 17550782
TI  - S6 kinase deletion suppresses muscle growth adaptations to nutrient availability
      by activating AMP kinase.
AB  - S6 kinase (S6K) deletion in metazoans causes small cell size, insulin
      hypersensitivity, and metabolic adaptations; however, the underlying molecular
      mechanisms are unclear. Here we show that S6K-deficient skeletal muscle cells
      have increased AMP and inorganic phosphate levels relative to ATP and
      phosphocreatine, causing AMP-activated protein kinase (AMPK) upregulation. Energy
      stress and muscle cell atrophy are specifically triggered by the S6K1 deletion,
      independent of S6K2 activity. Two known AMPK-dependent functions, mitochondrial
      biogenesis and fatty acid beta-oxidation, are upregulated in S6K-deficient muscle
      cells, leading to a sharp depletion of lipid content, while glycogen stores are
      spared. Strikingly, AMPK inhibition in S6K-deficient cells restores cell growth
      and sensitivity to nutrient signals. These data indicate that S6K1 controls the
      energy state of the cell and the AMPK-dependent metabolic program, providing a
      mechanism for cell mass accumulation under high-calorie diet.

PMID- 17550783
TI  - Dynamic visualization of the developing nervous system of the bullfrog, Rana
      catesbeiana.
AB  - Anuran amphibians undergo a rapid and dramatic process of metamorphosis featuring
      widespread structural reorganization of the central nervous system. Although
      morphological changes during embryonic stages of anuran development have been
      well documented, much less information is available describing structural changes
      in the brain during larval (tadpole) stages. Using still images from cresyl
      violet-stained material, we present an adaptation of the digital image and video
      manipulation technique of morphing that allows these images to be compiled in
      such a manner as to highlight key periods in tadpole brain development in a
      dynamic fashion. We present three morphed video data sets from ranid tadpoles
      that facilitate the identification of developmental changes in nuclear boundaries
      at different levels of the neuraxis. The use of animation allows dynamic
      examination of anatomical changes across long developmental spans without
      requiring additional anatomical preparations or specialized expensive equipment.

PMID- 17550784
TI  - Low serum adiponectin is independently associated with both the metabolic
      syndrome and angiographically determined coronary atherosclerosis.
AB  - BACKGROUND: We aimed at investigating serum adiponectin in patients with the
      metabolic syndrome (MetS), in patients with angiographically diagnosed coronary
      artery disease (CAD), and in patients who had both, the MetS and CAD. METHODS: We
      enrolled 687 consecutive patients undergoing coronary angiography for the
      evaluation of CAD. RESULTS: From our patients, 178 had neither the MetS (Adult
      Treatment Panel III definition) nor significant CAD (MetS-/CAD-), 91 had the
      MetS, but not significant CAD (MetS+/CAD-), 251 did not have the MetS but had
      significant CAD (MetS-/CAD+), and 167 had both, the MetS and significant CAD
      (MetS+/CAD+). Serum adiponectin was highest (12.1+/-8.3 microg/ml) in MetS-/CAD-
      subjects. It was significantly lower in MetS+/CAD- (9.5+/-7.3 microg/ml; p=0.001)
      and in MetS-/CAD+ patients (9.2+/-5.3 microg/ml; p<0.001) and lowest in
      MetS+/CAD+ patients (6.7+/-3.8 microg/ml) in whom it was significantly lower than
      in MetS-/CAD-, MetS+/CAD-, and MetS-/CAD+ patients (p<0.001 for all comparisons).
      In analysis of covariance the MetS and significant CAD proved associated with
      serum adiponectin in a mutually independent manner. CONCLUSIONS: Low serum
      adiponectin is independently associated with both the MetS and coronary
      atherosclerosis.

PMID- 17550785
TI  - Structures of ligand-free and inhibitor complexes of dihydroorotase from
      Escherichia coli: implications for loop movement in inhibitor design.
AB  - Dihydroorotase (DHOase) catalyzes the reversible cyclization of N-carbamyl-L
      aspartate (CA-asp) to L-dihydroorotate (DHO) in the de novo biosynthesis of
      pyrimidine nucleotides. DHOase is a potential anti-malarial drug target as
      malarial parasites can only synthesize pyrimidines via the de novo pathway and do
      not possess a salvage pathway. Here we report the structures of Escherichia coli
      DHOase crystallized without ligand (1.7 A resolution) and in the presence of the
      inhibitors 2-oxo-1,2,3,6-tetrahydropyrimidine-4,6-dicarboxylate (HDDP; 2.0 A) and
      5-fluoroorotate (FOA, 2.2 A). These are the first crystal structures of DHOase
      inhibitor complexes, providing structural information on the mode of inhibitor
      binding. HDDP possesses features of both the substrate and product, and ligates
      the Zn atoms in the active site. In addition, HDDP forms hydrogen bonds to the
      flexible loop (residues 105-115) stabilizing the "loop-in" conformation of the
      flexible loop normally associated with the presence of CA-asp in the active site.
      By contrast, FOA, a product-like inhibitor, binds to the active site in a similar
      fashion to DHO but does not ligate the Zn atoms directly nor stabilize the loop
      in conformation. These structures define the necessary features for the future
      design of improved inhibitors of DHOase.

PMID- 17550786
TI  - Acute hypertension in intracerebral hemorrhage: pathophysiology and treatment.
AB  - Non-traumatic or spontaneous intracerebral hemorrhage (ICH) is defined as intra
      parenchymal bleeding with or without extension into the ventricles and rarely
      into the subarachoid space. Primary ICH in most cases is associated with chronic
      hypertension. Acute hypertension is associated with hematoma expansion, and poor
      neurological outcome. The treatment of hypertension in acute ICH is a topic of
      controversy. Experiments have shown an area of ischemia around the hematoma, with
      the reduction of regional cerebral blood flow (CBF) secondary to compression of
      microvasculature. Not all scientific results agree with the above findings.
      Recent studies have shown that CBF decreases in the perihematoma region but with
      concomitant reduction of cerebral metabolism, which would argue against an area
      of ischemia in the perihematoma region. Based on the above result, there have
      been several clinical trials looking at clinical outcome and decrease in hematoma
      expansion rates with reduction of blood pressure acutely after ICH. The
      parameters for the blood pressure control are still under investigation. The
      American Heart Association has put forward guidelines for blood pressure control
      which have been adopted in the centers around the country. We have described the
      protocol we use at our center for the blood pressure control in patients with
      acute ICH.

PMID- 17550787
TI  - Effectiveness of quetiapine in rapid cycling bipolar disorder: a preliminary
      study.
AB  - OBJECTIVE: The authors examined long-term effectiveness and study retention
      during open-label quetiapine treatment for rapid cycling bipolar disorder.
      METHODS: An open-label, nonrandomized trial was conducted in 41 patients with
      rapid-cycling bipolar disorder (type I=33, type II=7, NOS=1) who received
      flexibly dosed quetiapine monotherapy (n=19) or add-on therapy (n=22) for up to
      one year. Linear growth curves were calculated to assess longitudinal changes in
      depression and mania. RESULTS: Linear growth curves demonstrated highly
      significant reductions in manic (p<.0001) and depressive (p<.0001) symptoms.
      Effect sizes were large against manic symptoms (add-on therapy: Cohen's d=0.66;
      monotherapy: Cohen's d=0.75) but small-to-moderate against depression
      (monotherapy: d=0.29; add-on therapy: d=0.40). Most patients (68%) prematurely
      terminated the protocol (mean duration: 18.0+/-16.9 weeks, mean dose: 195.6+/
      196.1 mg/day), most often because of the need for additional psychotropic
      treatments. LIMITATIONS: The study protocol involved an open label design with no
      placebo or active comparator group. The sample size provided adequate statistical
      power to detect large but not medium or small within-group effects. Premature
      dropout during the first six months precluded inferences about longer-term
      treatment outcome. CONCLUSIONS: These observational findings provisionally
      suggest some benefit with quetiapine for both manic and depressive symptoms in
      rapid cycling bipolar disorder, at dosages somewhat lower than previously
      described either for mania or bipolar depression. The relatively high dropout
      rate underscores the complexity of rapid cycling bipolar disorder and likely
      necessity for pharmacotherapy adjustments over time.

PMID- 17550788
TI  - A basal deuterostome genome viewed as a natural experiment.
AB  - With the determination of its genome sequence the utility of the sea urchin model
      system increases. The phylogenetic position of the sea urchin among the
      deuterostomes allows for informative comparisons to vertebrate research models. A
      combined whole genome shotgun and bacterial artificial chromosome based strategy
      yielded a high quality draft genome sequence of 814 Mb. The predicted gene set
      estimated to include 23,300 genes was annotated and compared to those of other
      metazoan animals. Gene family expansions in the innate immune system are large
      and offer a first glimpse of how the long-lived sea urchin defends itself. The
      gene sets of the sea urchin place it firmly among the deuterostomes and indicate
      that various gene family-specific expansions and contractions characterize the
      evolution of animal genomes rather than the invention of new genes.

PMID- 17550809
TI  - [The risk-benefit of high doses of botulinum toxin injections for muscle
      spasticity ].
AB  - OBJECTIVE: To bring general elements of reflection on the use of the high doses
      of botulinum toxin in spastic children and adults. MATERIAL AND METHODS: Review
      of the literature on the high doses and the benefit-risk associated with
      botulinum toxin injections. RESULTS: The medical literature exclusively relates
      to the use of the high doses in children and adolescents. Comparative work with
      conventional doses suggests a relative interest, but with a risk of increased
      side effects. Several articles report on treatments with high and even very high
      doses in series of patient, with a documented effectiveness. But their
      justification remains partial and the study of the possible side effects is
      limited. Reflections are brought to contribute to the debate on the use of high
      doses, taking into account the local physiological effect of botulinum toxin, the
      risk of regional and general diffusion, the need for a progressive strategy, the
      variability of effects, the cost of the treatment and the need for obtaining an
      informed consent of the patient and of significant others. CONCLUSION: The use of
      high doses of botulinum toxin increases progressively, but must remain very
      careful.

PMID- 17550810
TI  - [High doses of botulinum toxin, from efficacy to safety: experimental data].
AB  - Experimental studies in the animal have not been designed to specifically address
      the use of high doses of botulinum toxinum. However, it allows us to draw some
      very interesting findings. First, it has been showed that efficacy correlates to
      the dose, albeit up to a point beyond higher doses do not induce a greater
      benefit. Over this "ceiling" dose, the risk of migration outside the targeted
      muscle increases. The systemic risk is superior to the local risk. The efficacy
      could differ according to the number of injected muscles, and according to the
      type of toxin. What has been observed in the animals tend to be confirmed in
      human, despite precise studies are still lacking. Thus, experimental data support
      our daily clinical experience and provide us some very useful informations when
      high doses are injected. They especially help us to keep in mind the systemic
      risk which is, most of the time, unclear in our daily practice.

PMID- 17550811
TI  - [Multimuscle treatment of spasticity in adults patients with botulinum toxin].
AB  - Some recent studies in children with spasticity demonstrated the safety of
      multimuscle injections of botulinum toxin (BT) type A with doses markedly higher
      than those recommended. Data about efficacy and safety of multifocal injections
      of BT in adult patients with spasticity are very limited. However numerous
      clinical situations for example, spinal cord injury, multiple sclerosis, brain
      injury, stroke or cerebral palsy seem to justify this type of patient management.
      Controlled studies are expected in the future to evaluate the efficacy and safety
      of multisite injections of BT. They may encourage physicians to perform such
      multifocal injections with high doses of BT. A better understanding of distant
      spread of BT is also warranted.

PMID- 17550789
TI  - Structural and thermodynamic consequences of b heme binding for monomeric
      apoglobins and other apoproteins.
AB  - The binding of a cofactor to a protein matrix often involves a reorganization of
      the polypeptide structure. b Hemoproteins provide multiple examples of this
      behavior. In this minireview, selected monomeric and single b heme proteins
      endowed with distinct topological properties are inspected for the extent of
      induced refolding upon heme binding. To complement the data reported in the
      literature, original results are presented on a two-on-two globin of
      cyanobacterial origin (Synechococcus sp. PCC 7002 GlbN) and on the heme
      containing module of FixL, an oxygen-sensing protein with the mixed alpha/beta
      topology of PAS domains. GlbN had a stable apoprotein that was further stabilized
      and locally refolded by heme binding; in contrast, apoFixLH presented features of
      a molten globule. Sequence analyses (helicity, disorder, and polarity) and
      solvent accessibility calculations were performed to identify trends in the
      architecture of b hemoproteins. In several cases, the primary structure appeared
      biased toward a partially disordered binding pocket in the absence of the
      cofactor.

PMID- 17550812
TI  - [High doses of botulinum toxin type A in children: efficacy and safety in
      clinical practice].
AB  - The purpose of this article is to examine the current state of administering high
      doses botulinum toxin type A for the treatment of childhood spasticity,
      particularly Cerebral Palsy. The inter-relationship between the Cerebral Palsy
      neurological maturation and the early management is discussed, including
      identification of common gait patterns and the choice of target muscles for focal
      or multi focal spasticity management. High doses of botulinum toxin type A, when
      multilevel and integrated management approach is indicated, appear to be a safe,
      efficacious treatment for multi focal Cerebral Palsy spasticity. A review of
      literature guides the clinician about necessary adaptation of botulinum toxin
      doses and found no evidence that higher doses result in a increase of
      complications. Further studies would be interesting in order to evaluate long
      term safety and efficacy of this therapy in Cerebral Palsy.

PMID- 17550818
TI  - [Properly assessing respiratory syncytial virus epidemic].

PMID- 17550819
TI  - [Prevention of respiratory syncytial virus bronchiolitis].

PMID- 17550820
TI  - [Respiratory syncytial virus bronchiolitis: severe respiratory forms in
      hospitalized infants].

PMID- 17550821
TI  - Identification of three protein disulfide isomerase members from Haemaphysalis
      longicornis tick.
AB  - Three genes encoding putative protein disulfide isomerase (PDI) were isolated
      from the Haemaphysalis longicornis EST database and designed as HlPDI-1, HlPDI-2,
      and HlPDI-3. All three PDI genes contain two typical PDI active sites CXXC and
      encode putative 435, 499, and 488 amino acids, respectively. The recombinant
      proteins expressed in Escherichia coli all show PDI activities, and the
      activities were inhibited by a PDI-specific inhibitor, zinc bacitracin. Western
      blot analysis and real-time PCR revealed that three HlPDIs were present in all
      the developmental stages of the tick as well as in the midgut, salivary glands,
      ovary, hemolymph, and fatbody of adult female ticks, but the three genes were
      expressed at the highest level in the egg stage. HlPDI-1 is expressed primarily
      in the ovary and secondarily in the salivary glands. HlPDI-2 and HlPDI-3 are
      expressed primarily in the salivary gland, suggesting that the PDI genes are
      important for tick biology, especially for egg development, and that they play
      distinct roles in different tissues. Blood feeding induced significantly
      increased expression of HlPDI-1 and HlPDI-3 in both partially fed nymphs and
      adults. Babesia gibsoni-infected larval ticks expressed HlPDI-1 and HlPDI-3 2.0
      and 4.0 times higher than uninfected normal larval ticks, respectively. The
      results indicate that HlPDI-1 and HlPDI-3 might be involved in tick blood feeding
      and Babesia parasite infection in ticks.

PMID- 17550822
TI  - Immune upregulation of novel antibacterial proteins from silkmoths (Lepidoptera)
      that resemble lysozymes but lack muramidase activity.
AB  - Study on immune proteins in domesticated and wild silkmoths Bombyx mori and
      Antheraea mylitta, respectively, led to identification of a new class of
      antimicrobial proteins. We designated them as lysozyme-like proteins (LLPs) owing
      to their partial similarity with lysozymes. However, lack of characteristic
      catalytic amino acid residues essential for muramidase activity in LLPs puts them
      functionally apart from classical lysozymes. Two LLPs, one from B. mori (BLLP1)
      and the other from A. mylitta (ALLP1) expressed in a recombinant system,
      exhibited a broad-spectrum antibacterial action. Further investigation of the
      antibacterial mechanism revealed that BLLP1 is bacteriostatic rather than
      bactericidal against Escherichia coli and Micrococcus luteus. Substantial
      increase in hemolymph bacterial load was observed in B. mori upon RNA
      interference mediated in vivo knockdown of BLLP1. We demonstrate that the
      antibacterial mechanism of this protein depends on peptidoglycan binding unlike
      peptidoglycan hydrolysis or membrane permeabilization as observed with lysozymes
      and most other antimicrobial peptides. To our knowledge, this is the first report
      on functional analysis of novel, non-catalytic lysozyme-like family of
      antibacterial proteins that are quite apart functionally from classical
      lysozymes. The present analysis holds promise for functional annotation of
      similar proteins from other organisms.

PMID- 17550823
TI  - Molecular cloning and characterization of the complete acetylcholinesterase gene
      (Ace1) from the mosquito Aedes aegypti with implications for comparative genome
      analysis.
AB  - Insensitive acetylcholinesterase (AChE) has been shown to be responsible for
      resistance to organophosphates and carbamates in a number of arthropod species.
      Some arthropod genomes contain a single Ace gene, while others including
      mosquitoes contain two genes, but only one confers insecticide resistance. Here
      we report the isolation of the full-length cDNA and characterization of the
      complete genomic DNA sequence for the Ace1 gene in the yellow fever mosquito,
      Aedes aegypti. The Ace1 homolog in other mosquito species has been associated
      with insecticide resistance. The full-length cDNA consists of 2721bp and contains
      a 2109bp open reading frame that encodes a 702 amino acid protein. The amino acid
      sequence is highly conserved with that of other mosquitoes, including greater
      than 90% identity with Culex spp. and about 80% identity with Anopheles gambiae.
      The genomic DNA sequence includes 138,970bp and consists of eight exons with
      seven introns ranging from 59 to 114,350bp. Exons 2 and 8 show reduced amino acid
      conservation across mosquito species, while exons 3-7 are highly conserved. The
      Ace1 introns in Ae. aegypti reflect a high frequency of repetitive sequences that
      comprise about 45% of the total intron sequence. The Ace1 locus maps to the p-arm
      of chromosome 3, which corresponds to the orthologous genome regions in Culex
      spp. and An. gambiae.

PMID- 17550824
TI  - CPF and CPFL, two related gene families encoding cuticular proteins of Anopheles
      gambiae and other insects.
AB  - Cuticular proteins (CPs) are structural proteins of insects as well as other
      arthropods. Several CP families have been described, among them a small family
      defined by a 51 amino acid motif [Andersen, S.O., Rafn, K., Roepstorff, P., 1997.
      Sequence studies of proteins from larval and pupal cuticle of the yellow meal
      worm, Tenebrio molitor. Insect Biochem. Mol. Biol. 27, 121-131]. We identified
      four proteins of this family in Anopheles gambiae that we have named CPF. We have
      also identified CPFs from other insects by searching databases. Alignment of
      these CPF proteins showed that the conserved region is only 44 aa long and
      revealed another conserved motif at the C-terminus. A dendrogram divided the CPF
      proteins into four groups, one basal and three specialized. We also identified
      several proteins of another CP family, CPFL, which has similarities to CPFs. CPFs
      and CPFLs share some protein motifs. Expression studies with real-time qRT-PCR of
      the A. gambiae CPFs and CPFLs showed that the four CPFs and one CPFL gene are
      expressed just before pupal or adult ecdysis, suggesting that they are components
      of the outer layer of pupal and adult cuticles. The other CPFLs appear to
      contribute to larval cuticle. Recombinant CPF proteins did not bind to chitin in
      the assay we used.

PMID- 17550825
TI  - Genes encoding putative Takeout/juvenile hormone binding proteins in the honeybee
      (Apis mellifera) and modulation by age and juvenile hormone of the takeout-like
      gene GB19811.
AB  - We identified and characterized eight genes encoding putative Takeout/juvenile
      hormone binding proteins (To/JHBP) in the honeybee genome. Phylogenetic analyses
      revealed nine distinct lineages within this gene family, including those
      containing Takeout (To) and JHBP for which there are no honeybee homologs. Their
      diversity and ubiquitous expression suggest that To/JHBP proteins are involved in
      diverse and important processes in insects. We further characterized the
      expression of one of these genes, GB19811 that is ubiquitously expressed. GB19811
      transcript levels in the abdomen increased, and decreased in the head with worker
      age. There was no influence of colony environment or brood care behavior on
      GB19811 expression in young bees. Young bees treated with juvenile hormone (JH)
      showed a decrease in head GB19811 mRNA levels. This finding is consistent with
      the premise that JH, for which titers typically increase with age, is involved in
      age-related modulation of GB19811 expression. In contrast to Drosophila Takeout,
      the expression of GB19811 did not vary with diurnal or circadian rhythms. Taken
      together, these findings suggest that GB19811 is not an ortholog of Takeout, and
      is involved in JH-mediated regulation of adult honeybee worker development.

PMID- 17550827
TI  - Structure and function of 5'-flanking regions of Bombyx mori fibroin heavy chain
      gene: identification of a novel transcription enhancing element with a
      homeodomain protein-binding motif.
AB  - We studied the promoter activity of a 5'-flanking region from -5000 to +24 (
      5000/+24) in Bombyx mori fibroin heavy chain gene (fibH), fibH(-5000/+24). A
      luciferase reporter vector carrying fibH(-5000/+24) was bombarded to isolated
      posterior silk glands (PSGs). The PSGs showed a high luciferase activity when
      transplanted to larvae, indicating its potent promoter activity. Deletion
      experiments showed the requirement of fibH(-5000/-3844) and fibH(-2211/-542) for
      the promoter activity. These two regions and fibH(-541/+24) that contained the
      basal promoter were tandem fused to yield fibH(-5000/-3844:-2211/-542:-541/+24),
      which was found to retain 88% of the activity of fibH(-5000/+24). Germline
      transgenic silkworms bearing fibH(-5000/-3844:-2211/-542:-541/+24) as a promoter
      and enhanced green fluorescent protein (EGFP) gene as a reporter efficiently
      secreted EGFP in cocoons. The promoter activity of fibH(-2211/-542) was further
      investigated, because this contained a DNase I-hypersensitive site. The transient
      expression assay demonstrated that the activity of fibH(-2211/-542) required
      fibH(-1659/-1590), which contained the homeodomain protein-binding motif.
      Mutation experiments suggested a critical role of the motif for the promoter
      activity. Electrophoretic mobility shift assay (EMSA) demonstrated that a nuclear
      protein of PSGs bound to the motif. We propose fibH(-1659/-1590) as a novel
      transcription enhancer that plays a key role for the expression by recruiting a
      homeodomain protein.

PMID- 17550826
TI  - The sialotranscriptome of the blood-sucking bug Triatoma brasiliensis (Hemiptera,
      Triatominae).
AB  - Triatoma brasiliensis is the most important autochthon vector of Trypanosoma
      cruzi in Brazil, where it is widely distributed in the semiarid areas of the
      Northeast. In order to advance the knowledge of the salivary biomolecules of
      Triatominae, a salivary gland cDNA library of T. brasiliensis was mass sequenced
      and analyzed. Polypeptides were sequenced by HPLC/Edman degradation experiments.
      Then 1712 cDNA sequences were obtained and grouped in 786 clusters. The
      housekeeping category had 24.4% and 17.8% of the clusters and sequences,
      respectively. The putatively secreted category contained 47.1% of the clusters
      and 68.2% of the sequences. Finally, 28.5% of the clusters, containing 14% of all
      sequences, were classified as unknown. The sialoma of T. brasiliensis showed a
      high amount and great variety of different lipocalins (93.8% of secreted
      proteins). Remarkably, a great number of serine proteases that were not observed
      in previous blood-sucking sialotranscriptomes were found. Nine Kazal peptides
      were identified, among them one with high homology to the tabanid vasodilator
      vasotab, suggesting that the Triatoma vasodilator could be a Kazal protein.

PMID- 17550828
TI  - Identification of immune-related genes from an apterygote insect, the firebrat
      Thermobia domestica.
AB  - In this study, we report the analysis of the immune-related transcriptome from an
      apterygote insect, the firebrat Thermobia domestica (Zygentoma, Lepismatidae),
      which currently emerges as a suitable model insect for evolutionary and
      developmental studies. The suppression subtractive hybridization method was used
      for targeted screening of genes that are up-regulated in response to injected
      bacterial lipopolysaccharide (LPS). A subtracted cDNA library enriched in immune
      inducible genes was constructed and analysis of 288 cDNAs resulted in
      identification of 26 novel genes in T. domestica. Among these immune-related
      transcripts we found homologues of genes from other insects which are involved in
      the regulation of signaling cascades and six novel putative antimicrobial
      peptides. The identified genes implicate the presence of sophisticated regulatory
      mechanisms in insect immune signaling and give insight into evolutionarily
      conserved features of insect innate immunity.

PMID- 17550829
TI  - Tissue-specific gene silencing by RNA interference in the whitefly Bemisia tabaci
      (Gennadius).
AB  - The hemipteran whitefly Bemisia tabaci (Gennadius) species complex and the plant
      viruses they transmit pose major constraints to vegetable and fiber production,
      worldwide. The whitefly tissue- and developmental-specific gene expression has
      not been exhaustively studied despite its economic importance. In 2002, a
      functional genomic project was initiated, which generated several thousands
      expressed sequence tags (ESTs) and their sequence. This project provides the
      basic information to design experiments aimed at understanding and manipulating
      whitefly gene expression. In this communication, for the first time we provide
      evidence that the RNA interference mechanism discovered in many organisms,
      including in Hemiptera, is active in B. tabaci. By injecting into the body cavity
      long double-stranded RNA (dsRNA) molecules, specifically directed against genes
      uniquely expressed in the midgut and salivary glands, we were able to
      significantly inhibit the expression of the targeted mRNA in the different
      organs. Gene expression levels in RNAi-silenced whiteflies were reduced up to 70%
      compared to whiteflies injected with buffer or with a green fluorescent protein
      (GFP)-specific dsRNA. Phenotypic effects were observed in B. tabaci ovaries
      following dsRNA targeting the whitefly Drosophila chickadee homologue. Disruption
      of whitefly gene expression opens the door to new strategies aimed at curbing
      down the deleterious effects of this insect pest to agriculture.

PMID- 17550830
TI  - [Assisted reproduction, failed responses. Reports from a conference, 16 September
      2006, Asnieres sur Oise, France].

PMID- 17550841
TI  - Pyruvate kinase deficiency.

PMID- 17550842
TI  - The spectrum of molecular aberrations in myelodysplastic syndromes: in the shadow
      of acute myeloid leukemia.

PMID- 17550843
TI  - Myeloproliferative disorders: let the partner guide!

PMID- 17550844
TI  - Transgenic rescue of hemolytic anemia due to red blood cell pyruvate kinase
      deficiency.
AB  - BACKGROUND AND OBJECTIVES: Red blood cell pyruvate kinase (R-PK) deficiency is
      the most common glycolytic enzyme defect associated with hereditary non
      spherocytic hemolytic anemia. Cases with the most severe deficiency die in the
      peri- or neonatal period and no specific therapy exists at present. To test
      whether the targeted overexpression of the normal R-PK gene in erythroid cells
      could reduce hemolysis in R-PK mutant mice, we performed a genetic rescue study
      using human R-PK transgenic mice. DESIGN AND METHODS: Human R-PK promoter driven
      with human mLCR of the human b-globin locus was used for the erythroid-specific
      expression of human R-PK in murine erythrocytes. The transgenic lines were mated
      with homozygous R-PK mutant mice and subsequently backcrossed. Mutant homozygotes
      with the mLCR-R-PK transgene were examined for any therapeutic effects of
      transgene expression. RESULTS: Two PK transgenic lines, hRPK_lo and hRPK_hi, were
      obtained. R-PK activity of the transgenic mice reached as high as three times
      that of the animals with the endogenous PK gene. Overexpression of human R-PK in
      the homozygous mutant mice successfully reduced hemolytic anemia. Improvements of
      hemolysis were evaluated by hemoglobin concentration, reticulocyte count, and
      spleen weight, which showed significant correlations with the levels of
      expression of the transgene. Recovery from metabolic disturbance in mutant red
      blood cells was shown as normalized concentrations of the glycolytic
      intermediates upstream of PK. In addition, there was a remarkable negative
      correlation between R-PK activity and the number of TUNEL-positive erythroid
      progenitors in the spleen. INTERPRETATION AND CONCLUSIONS: These results indicate
      that overexpression of the wild-type PK gene in mutant erythroid cells
      ameliorates both erythroid apoptosis and the shortened red blood cell lifespan
      observed in PK mutant mice. It is likely that the level of transgene expression
      required to achieve evident therapeutic effects should be equivalent to or more
      than that of the endogenous PK gene. This gene-addition strategy may be suitable
      for clinical application if there is a high level of transgene expression of R-PK
      in erythroid progenitors/red blood cells.

PMID- 17550845
TI  - Pulmonary hypertension in patients with sickle cell/beta thalassemia: incidence
      and correlation with serum N-terminal pro-brain natriuretic peptide
      concentrations.
AB  - BACKGROUND AND OBJECTIVES: Pulmonary hypertension (PH) is increasingly observed
      in sickle cell disease (SCD) and beta-thalassemia (beta-thal), but there is no
      information on its prevalence in patients with HbS/beta-thal. The amino-terminal
      fragment of B-type natriuretic peptide (NT-proBNP) is considered as an
      independent prognostic factor in PH. The aim of this study was to evaluate the
      incidence of PH and its correlation with clinical and laboratory findings,
      including NT-proBNP, in patients with HbS/beta-thal. DESIGN AND METHODS: We
      studied 84 HbS/beta-thal patients; 51% had been receiving hydroxyurea for a
      median time of 9 years. The presence of PH was evaluated using Doppler
      echocardiography and NT-proBNP serum levels were determined by an
      electrochemiluminescence immunoassay. RESULTS: The incidence of PH in our cohort
      of HbS/beta-thal patients was 33%. PH patients had elevated values of NT-proBNP,
      reticulocyte counts and serum ferritin compared with patients without PH.
      However, even patients without PH had elevated concentrations of NT-proBNP
      compared with controls. An NT-proBNP level of 153.6 pg/mL had the highest
      sensitivity (85.7%) and specificity (94.6%) for detecting PH in our patients. NT
      proBNP levels correlated with measures of pulmonary artery systolic pressure
      (tricuspid regurgitant jet velocity and right ventricular systolic pressure),
      left atrial area and diastolic dysfunction. The administration of hydroxyurea did
      not affect the presence of PH. INTERPRETATION AND CONCLUSIONS: The incidence of
      PH in patients with HbS/beta-thal is similar to that observed in patients with
      SCD. Serum NT-proBNP is a strong indicator of PH in HbS/beta-thal. The
      correlation between PH and reticulocyte counts and ferritin suggests that the
      degree of hemolysis and iron overload is implicated in the pathogenesis of PH in
      HbS/beta-thal.

PMID- 17550846
TI  - A comparative study of molecular mutations in 381 patients with myelodysplastic
      syndrome and in 4130 patients with acute myeloid leukemia.
AB  - BACKGROUND AND OBJECTIVES: The precise relationship between myelodysplastic
      syndrome (MDS) and acute myeloid leukemia (AML) is unclear and the role of
      molecular mutations in leukemic transformation in MDS is controversial. The aim
      of this study was to clarify the relationship between AML and MDS by comparing
      the frequency of molecular mutations in the two conditions. DESIGN AND METHODS:
      We compared the frequency of FLT3-length mutations (FLT3-LM), FLT3-TKD, MLL
      partial tandem duplications (MLL-PTD), NRAS, and KITD816 in 381 patients with MDS
      refractory anemia with excess blasts [RAEB] n=49; with ringed sideroblasts [RARS]
      n=310; chronic monomyelocytic leukemia [CMML] n=22) and in 4130 patients with AML
      (de novo: n=3139; secondary AML [s-AML] following MDS: n=397; therapy-related [t
      AML]: n=233; relapsed: n=361). RESULTS: All mutations were more frequent in s-AML
      than in MDS and all but the FLT3-TKD were more frequent in RAEB than in RA/RARS.
      The higher incidences in s-AML were significant for FLT3-TKD (p=0.032), MLL-PTD
      (p=0.034), and FLT3-LM (RA/RARS: 0/45; RAEB: 8/293; 2.7%; s-AML: 45/389; 11.6%;
      p<0.0001). The incidence of NRAS-mutations increased from 17/272 (6.3%) in MDS to
      41/343 in s-AML (12.0%) and that of KITD816-mutations from 2/290 (0.7%) to 5/341
      (1.5%) (p=n.s.). FLT3-LM-acquisition occurred in 3/22 cases (13.6%) during MDS
      transformation; NRAS-acquisition occurred in 1/24 (4.2%). FLT3-LM and MLL-PTD
      were more frequent in AML relapse than in de novo AML or s-AML (p<0.0001).
      INTERPRETATION AND CONCLUSIONS: The increase of molecular mutations from low- to
      high-risk MDS, to s-AML, and to relapsed AML emphasizes the value of these
      mutations as markers of progressing disease. Finally, we found a low rate of 5q-
      in the molecularly mutated cases in MDS which might explain the stability of this
      subtype.

PMID- 17550847
TI  - Arsenic trioxide induces accumulation of cytotoxic levels of ceramide in acute
      promyelocytic leukemia and adult T-cell leukemia/lymphoma cells through de novo
      ceramide synthesis and inhibition of glucosylceramide synthase activity.
AB  - BACKGROUND AND OBJECTIVES: Arsenic trioxide (ATO) is an effective treatment for
      acute promyelocytic leukemia (APL) and potentially for human T-cell leukemia
      virus type I (HTLV-I) associated adult T-cell leukemia/lymphoma (ATL). Many
      cytotoxic drugs induce apoptosis through the generation and accumulation of the
      sphingolipid breakdown product, ceramide, a coordinator of the cellular response
      to stress. We, therefore, investigated the contribution of ceramide to the
      mechanism of action of ATO in APL and ATL. DESIGN AND METHODS: A human APL
      derived cell line (NB4), various ATL-derived lines and an HTLV-I-negative
      malignant T-cell line were cultured and treated with ATO. Growth and apoptosis
      assays were conducted. Measurements were made of ceramide, diacylglycerol,
      sphingomyelinase activity, sphingomyelin mass, glucosylceramide synthase activity
      and the de novo ceramide synthesis. RESULTS: Treatment of APL and ATL-derived
      cells with a clinically achievable concentration of ATO induced accumulation of
      cytotoxic levels of ceramide. The effects of ATO on ceramide levels in APL cells
      were more potent than those of all-trans retinoic acid (ATRA). ATO downregulated
      neutral sphingomyelinase activity. In contrast to the effect of ATRA, ATO-induced
      ceramide accumulation was not due to induction of acidic sphingomyelinase, but
      rather resulted from both de novo ceramide synthesis and inhibition of
      glucosylceramide synthase activity. Interestingly, the effects of ATO on de novo
      ceramide synthesis were similar in APL and ATL-derived cells despite the
      defective pathway in ATL cells. INTERPRETATION AND CONCLUSIONS: These results
      indicate that ATO-induced ceramide accumulation may represent a general mediator
      of the effects of ATO, which paves the way for new therapeutic interventions that
      target the metabolic pathway of this important sphingolipid secondary messenger.

PMID- 17550848
TI  - Prognosis of acute myeloid leukemia patients up to 60 years of age exhibiting
      trisomy 8 within a non-complex karyotype: individual patient data-based meta
      analysis of the German Acute Myeloid Leukemia Intergroup.
AB  - BACKGROUND AND OBJECTIVES: Trisomy 8 (+8) is among the commonest genetic
      aberrations seen in acute myeloid leukemia (AML). However, the prognostic
      significance of this aberration and the best consolidation strategy for patients
      with it are still not resolved. Additional prognostic indicators are needed to
      further classify these patients and determine their appropriate management.
      DESIGN AND METHODS: Individual patient data-based meta-analysis was performed on
      131 patients (median age 50 (18-60) years) with +8 as a sole aberration or +8
      with one additional aberration treated between 1993 and 2002 in eight prospective
      German AML treatment trials. All patients received state-of-the-art treatment
      including high-dose cytarabine with the option for autologous or allogeneic
      hematopoietic stem cell transplantation (HSCT). RESULTS: In total, the 131
      patients had a 3-year overall survival (OS) of 29% and a 3-year relapse-free
      survival (RFS) of 32%. Independent prognostic factors contributing to shorter OS
      were age > or = 45 years, extramedullary disease, and a percentage of +8 positive
      metaphases >/=80%. Combining these three prognostic variables established a
      hierarchical model for OS. The 3-year OS was 13% for the high-risk group, 36% for
      the intermediate-risk group, and 55% for the low-risk group (p<0.0001). Age <45
      years and allogeneic HSCT (as treated) were independent prognostic factors for
      longer RFS. Additional cytogenetic aberrations other than t(8;21), inv(16),
      t(16;16), t(15;17) or 11q23 had no influence on treatment outcome. INTERPRETATION
      AND CONCLUSIONS: We provide a new prognostic model for risk stratification of AML
      patients with +8. The data indicate that allogeneic HSCT may prolong RFS compared
      to that achieved with other strategies of post-remission therapy.

PMID- 17550849
TI  - Histological verification of positive positron emission tomography findings in
      the follow-up of patients with mediastinal lymphoma.
AB  - BACKGROUND AND OBJECTIVES: Follow-ups of patients with mediastinal lymphoma are
      not accurate if they rely on computed tomography (CT). Positron emission
      tomography (PET) has been suggested to be useful in several lymphoma settings,
      such as initial staging, evaluation of residual masses after therapy, and
      assessment of response early in the course of treatment. The aim of this
      retrospective study was to verify the reliability of positive PET scans of the
      mediastinum in following up patients with mediastinal lymphoma, using
      histological findings as a comparison. DESIGN AND METHODS: From January 2002 to
      July 2005, 151 patients with mediastinal lymphoma (57 with Hodgkin's disease [HD]
      and 94 with aggressive non-Hodgkin's lymphoma [NHL]) were followed-up after the
      end of front-line treatment. Patients with a positive PET scan of the mediastinum
      underwent CT scanning and surgical biopsy. RESULTS: In 30 (21 HD and 9 NHL) out
      of 151 patients (20%) a suspicion of lymphoma relapse was raised based on
      positive mediastinal PET scanning. Histology confirmed this suspicion in 17 (10
      HD and 7 NHL) out of 30 patients (57%), whereas either benign (9 fibrosis, 3
      sarcoid-like granulomatosis) or unrelated neoplastic conditions (1 thymoma) were
      demonstrated in the remaining 13 patients (43%). SUVmax was significantly higher
      among patients who had signs of relapse (17 true positive cases) than among those
      who stayed in remission (13 false positive cases), the median values being 5.95
      (range, 3.5-26.9) and 2.90 (range, 1.4-3.3), respectively (p=0.01).
      INTERPRETATION AND CONCLUSIONS: We suggest that a positive PET scan of the
      mediastinum of a patient being followed-up for a mediastinal lymphoma should not
      be considered sufficient for diagnostic purposes in view of its lack of
      discrimination. Histological confirmation can safely be carried out with various
      biopsy techniques, the choice of which should be made on the basis of the
      findings of the clinical and imaging studies of the individual case.

PMID- 17550850
TI  - Respective prognostic values of germinal center phenotype and early
      (18)fluorodeoxyglucose-positron emission tomography scanning in previously
      untreated patients with diffuse large B-cell lymphoma.
AB  - BACKGROUND AND OBJECTIVES: Diffuse large B-cell lymphomas (DLBCL) have a variable
      outcome, and powerful methods of prognostication are needed in order to choose
      the best treatment for each patient. Immunophenotypic classification of the tumor
      as germinal center (GC) or non-germinal center-like (nGC) and early response
      evaluation with 18fluorodeoxyglucose positron emission tomography (18FDG-PET)
      scanning have been correlated with survival in DLBCL but the two methods have
      never been evaluated simultaneously in the same patient population. Our aim was
      to investigate their respective prognostic values in the same series of patients.
      DESIGN AND METHODS: We investigated the expression of CD10, Bcl-6, and MUM1 in 81
      patients with DLBCL evaluated early with 18FDG-PET. The tumors were classified as
      GC or nGC using the algorithm of Hans et al. The results of both methods were
      correlated with the patients' characteristics and survival. RESULTS: CD10 was
      positive in 27/76 (36%), Bcl-6 in 43/74 (58%), and MUM1 in 33/73 (45%)
      interpretable cases. Thirty-eight (51%) were in the GC group, and 36 (49%) in the
      nGC group. With a median follow-up of 33 months, estimated 3-year event-free
      survival (EFS) of the whole population was 67%. There was no influence of GC/nGC
      phenotype on survival. Three-year EFS was 46% in the early PET-positive group
      versus 80% in the PET-negative group (p=0.0003). INTERPRETATION AND CONCLUSIONS:
      The prognostic value of GC/nGC phenotype is not confirmed in this heterogeneous
      series, whereas early PET findings are confirmed to be a powerful predictor of
      outcome. The impact of treatment decisions based on early PET results should be
      evaluated.

PMID- 17550851
TI  - Low-dose intermittent alemtuzumab in the treatment of Sezary syndrome: clinical
      and immunologic findings in 14 patients.
AB  - BACKGROUND AND OBJECTIVES: Alemtuzumab may be effective in Sezary syndrome (SS),
      an aggressive cutaneous T-cell lymphoma, but is associated with severe
      hematologic toxicity and infections. This study investigated whether low-dose
      subcutaneous alemtuzumab can induce hematologic, immunologic, and clinical
      responses similar to those obtained with the standard regimen, but with less
      toxicity. DESIGN AND METHODS: Fourteen SS patients were enrolled: 11 had
      relapsed/refractory disease and three had untreated SS with high counts of
      circulating Sezary cells (SC). Four received 3 mg alemtuzumab on day 1, 10 mg on
      day 3, then 15 mg on alternating days; circulating SC were evaluated after the
      fourth 15 mg dose and treatment was interrupted in the presence of counts
      <1,000/mm (3). A reduced dosage (3 mg on day 1, then 10 mg on alternating days)
      was administered to the remaining patients, with SC counted before every
      injection, until a reduction to values of <1,000/mm (3). RESULTS: The median SC
      count decreased by 95.5%. Overall, 12/14 patients (85.7%) achieved a clinical
      response, with three complete responses (21.4%). After a median follow-up of 16
      months, the median time-to-treatment failure is 12 months. Infectious
      complications occurred in 28.6% of patients, all included in the group treated
      with 15 mg. No patient in the group treated with 10 mg developed hematologic
      toxicity or infections. An early recovery of circulating NK, B and CD3+CD8+ cells
      occurred after the first cycle. INTERPRETATION AND CONCLUSIONS: Subcutaneous
      alemtuzumab at very low doses (10 mg maximum per administration), given for a
      short period based on SC levels, has a good toxicity profile, high response rate
      and causes durable remissions in SS patients with high tumor burden in the
      peripheral blood.

PMID- 17550852
TI  - Multiple myeloma primary cells show a highly rearranged unbalanced genome with
      amplifications and homozygous deletions irrespective of the presence of
      immunoglobulin-related chromosome translocations.
AB  - BACKGROUND AND OBJECTIVES: Multiple myeloma (MM) is a malignant plasma cell
      neoplasia in which genetic studies have shown that genomic changes may affect
      almost all chromosomes, as shown by fluorescence in situ hybridization (FISH) and
      comparative genomic hybridization (CGH). Our objective was the genomic
      characterization of CD 138 positive primary MM samples by means of a high
      resolution array CGH platform. DESIGN AND METHODS: For the first time, a high
      resolution array CGH with more than 40,000 probes, has been used to analyze 26
      primary MM samples after the enrichment of CD138-positive plasma cells. RESULTS:
      This approach identified copy number imbalances in all cases. Bioinformatics
      strategies were optimized to perform data analysis allowing the segregation of
      hyperdiploid and non-hyperdiploid cases by array CGH. Additional analysis showed
      that structural chromosome rearrangements were more frequently seen in
      hyperdiploid cases. We also identified the same Xq21 duplication in nearly 20% of
      the cases, which originated through unbalanced chromosome translocations. High
      level amplifications and homozygous deletions were recurrently observed in our
      series and involved genes with meaningful function in cancer biology.
      INTERPRETATION AND CONCLUSIONS: High resolution array CGH allowed us to identify
      copy number changes in 100% of the primary MM samples. We segregated different MM
      subgroups based on their genomic profiles which made it possible to identify
      homozygous deletions and amplifications of great genetic relevance in MM.

PMID- 17550853
TI  - TACI expression is associated with a mature bone marrow plasma cell signature and
      C-MAF overexpression in human myeloma cell lines.
AB  - BACKGROUND AND OBJECTIVES: BAFF and APRIL stimulate the growth of multiple
      myeloma (MM) cells. BAFF and APRIL share two receptors--TACI and BCMA--and BAFF
      binds to a third receptor, BAFF-R. We previously reported that TACI gene
      expression is bimodal in 18 human MM cell lines (HMCL), being either present or
      absent, unlike BCMA that is expressed on all HMCL. BAFF-R is lacking. TACI
      expression is a good indicator of a BAFF-binding receptor in HMCL. In primary MM
      cells, the level of TACI expression correlates with a characteristic phenotypic
      pattern: TACIhighMM cells resemble bone marrow plasma cells and TACIlow resemble
      plasmablasts. The aim of this study was to further characterize the role of TACI
      expression in MM DESIGN AND METHODS: Using gene expression profiling, we
      investigated whether these patterns are kept in TACI+ or TACI- HMCL. RESULTS:
      Eighty genes/EST interrogated by Affymetrix microarrays were differentially
      expressed between TACI+ and TACI- HMCL, particularly c-maf, cyclin D2, and
      integrin beta7. Triggered by the finding that TACI and c-maf expressions
      correlate in TACI+ HMCL, we demonstrated that TACI activation influences c-maf
      expression: (i) activation of TACI by BAFF or APRIL increases c-maf, cyclin D2,
      and integrin beta7 gene expressions in TACI+ HMCL, (ii) blocking of autocrine
      BAFF/APRIL stimulation in some TACI+ HMCL by the TACI-Fc fusion protein reduces c
      maf, cyclin D2, and integrin beta7 gene expression, (iii) nucleofection of siRNA
      to c-maf decreases c-maf mRNA levels and reduces the expression of cyclin D2 and
      integrin beta7 gene expressions, without affecting TACI expression INTERPRETATION
      AND CONCLUSIONS: We conclude that TACI activation can upregulate c-maf expression
      which, in turn, controls cyclin D2, and integrin beta7 gene expression.

PMID- 17550854
TI  - Endothelial dysfunction in patients with spontaneous venous thromboembolism.
AB  - BACKGROUND AND OBJECTIVES: A high incidence of atherosclerotic lesions and
      cardiovascular events has been reported in patients with spontaneous venous
      thromboembolism. Endothelial dysfunction is an early marker of atherosclerosis
      and has predictive value for ischemic events. We have evaluated endothelial
      function in patients with a history of spontaneous venous thromboembolism. DESIGN
      AND METHODS: Patients with a history of symptomatic, objectively confirmed,
      spontaneous venous thromboembolism were included in a case-control study.
      Exclusion criteria were any known risk factors for cardiovascular diseases, other
      conditions associated with endothelial dysfunction, estro-progestinic therapy or
      pregnancy. Controls were age- (+/-5 years) and sex-matched subjects with the same
      exclusion criteria but without previous venous thromboembolism. Endothelial
      function was evaluated by the non-invasive measurement of flow-mediated
      vasodilation of the brachial artery and of plasma markers of endothelium
      activation; platelet activation parameters were also measured. RESULTS: Twenty
      eight cases (8 females; mean age 59+/-15 years) and 28 controls (8 females; mean
      age 58+/-15) were studied. Flow-mediated vasodilation was 3.5+/-0.6% in cases
      (95% CIs: 2.2 to 4.8) and 5.7+/-0.6% (4.2 to 6.8) in controls (p=0.015). Brachial
      artery blood flow and hyperemic blood flow did not differ between the two groups.
      Plasma von Willebrand factor and soluble P-selectin levels were significantly
      higher in patients with venous thromboembolism, while plasma soluble CD40 ligand
      and urinary 11-dehydro-TxB2 levels were similar in cases and controls.
      INTERPRETATION AND CONCLUSIONS: Patients with spontaneous venous thromboembolism
      have endothelial dysfunction, unlike age- and sex- matched controls. This finding
      suggests that spontaneous venous thromboembolism may be a condition associated
      with an enhanced risk of atherosclerosis.

PMID- 17550855
TI  - Retrospective evaluation of serum Epstein Barr virus DNA levels in 406 allogeneic
      stem cell transplant patients.
AB  - BACKGROUND AND OBJECTIVES: An HLA-mismatched donor and a T-cell-depleted graft
      are known risk factors for Epstein-Barr virus (EBV) reactivation after stem cell
      transplantation. We studied the frequency and outcome of serum EBV DNA levels in
      patients transplanted with an unmanipulated graft from an HLA-identical donor.
      DESIGN AND METHODS: Overall, 5479 serial serum samples from 406 consecutive
      allogeneic stem cell transplant recipients were analyzed retrospectively for EBV
      DNA with quantitative polymerase chain reaction (PCR). RESULTS: EBV DNA was found
      in the serum of 56 of the 406 patients (14%). EBV positivity was seen in 9 % of
      the recipients of a graft from a sibling donor and in 29 % of those with an
      unrelated donor. EBV-PCR positivity resolved without specific treatment in a
      third of the cases, in another third the copy number increased progressively or
      was high in the last serum sample, and in the remaining third the copy numbers
      were low in all positive sera including the last sample. In multivariate analysis
      antithymocyte globulin given for any reason and grade III-IV acute graft-versus
      host disease were the only statistically significant risk factors for EBV
      reactivation. Only 8/56 patients with EBV-DNA positivity were alive at the time
      of the present analysis. The outcome of EBV-PCR positivity could not be predicted
      by the copy number or the timing of the first positive sample. INTERPRETATION AND
      CONCLUSIONS: EBV reactivation was a common phenomenon in allogenic stem cell
      transplant recipients. In many patients the viremia resolved without EBV-directed
      treatment. Severe acute graft-versus-host disease and antithymocyte globulin
      given for any reason were risk factors for EBV viremia.

PMID- 17550856
TI  - Rituximab maintenance therapy: a step forward in follicular lymphoma.
AB  - Whilst recent advances in the treatment of follicular lymphoma (FL) have improved
      the outlook for many patients, relapses still occur and the search continues for
      strategies to extend the duration of remission without significantly increasing
      toxicity. One such strategy is the use of rituximab maintenance therapy for
      patients responding to initial induction. There is now a large body of evidence
      demonstrating clear benefits of rituximab maintenance versus observation
      following induction with either rituximab plus chemotherapy (R chemo),
      chemotherapy alone, or rituximab monotherapy, in both first-line and
      relapsed/refractory settings. A very important finding is that rituximab
      maintenance can significantly improve overall survival in FL patients responding
      to induction with either R-chemo or chemotherapy alone. Also, compared with
      rituximab retreatment at disease progression, the maintenance approach produces
      much better complete remission rates and significantly longer continuous
      remissions and progression-free survival. Various maintenance schedules have been
      explored, all of which demonstrate clear benefits. However, the optimal dose,
      schedule, and duration of maintenance therapy still need to be established.
      Current data indicate that rituximab maintenance can be safely administered for
      up to 2 years, although assessment of long-term safety requires longer follow-up.
      From the patient's perspective, rituximab maintenance also prolongs the period in
      which patients are symptom-free and able to lead a relatively normal daily life.
      Also, rituximab maintenance may help patients feel they can control their
      disease, rather than passively waiting for relapse.

PMID- 17550857
TI  - Dynamics of cytogenetic aberrations in Philadelphia chromosome positive and
      negative hematopoiesis during dasatinib therapy of chronic myeloid leukemia
      patients after imatinib failure.
AB  - Clonal cytogenetic aberrations of the Philadelphia chromosome (Ph) positive
      hematopoiesis have been associated with the natural evolution of chronic myeloid
      leukemia (CML) to advanced disease. Clonal aberrations of Ph negative metaphases
      have been described after treatment with interferon or imatinib. This study
      evaluates the effect of dasatinib on Ph positive clones with additional
      cytogenetic aberrations and the frequency of novel aberrations in Ph positive and
      negative metaphases. Seventy-one patients treated with dasatinib after imatinib
      failure for a median of nine months were evaluated. Novel aberrations within Ph
      positive and negative clones appeared in six and three patients, respectively.

PMID- 17550858
TI  - Enhanced Bcr-Abl-specific antileukemic activity of arsenic trioxide (Trisenox)
      through glutathione-depletion in imatinib-resistant cells.
AB  - The development of resistance to imatinib mesylate may partly depend on high Bcr
      Abl-expression levels. Arsenic trioxide (ATO) has Bcr-Abl suppressing activity in
      vitro. Here we investigated means to improve ATO activity in CML by modulating
      cellular glutathione (GSH), a key regulator of ATO-activity in malignant disease.
      Our studies demonstrate that depletion of cellular glutathione using dl
      buthionine-[S,R]-sulfoximine (BSO) enhances ATO activity against CML cells. GSH
      depletion promotes enhanced Bcr-Abl specific activity of ATO through avid
      repression of Bcr-Abl protein levels and total cellular Bcr-Abl activity. These
      data provide a rationale for the clinical development of optimized ATO-based
      regimens through incorporation of GSH-modulators in CML treatment.

PMID- 17550859
TI  - Sixteen novel hemophilia A causative mutations in the first Argentinian series of
      severe molecular defects.
AB  - Hemophilia A (HA) is caused by heterogeneous mutations in the factor VIII gene
      (F8). This paper reports 16 novel small F8-mutations and rearrangements in a
      series of 80 Argentinian families with severe-HA. Using an updated scheme for F8
      analysis, we found 37 F8-inversions (46%), 10 large deletions (13%), 13 small
      ins/del (16%), 7 nonsense (9%) and 8 missense mutations (10%), including 4 new
      ones (p.T233K, p.W1942R, p.L2297P and p.L2301S). The potential changes leading to
      severe-HA of these latter mutations were suggested by bioinformatics. The F8
      mutation was characterised in 76 families (95%). They received genetic
      counselling and precise information about treatment design.

PMID- 17550860
TI  - Cryoprecipitate versus commercial fibrinogen concentrate in patients who
      occasionally require a therapeutic supply of fibrinogen: risk comparison in the
      case of an emerging transfusion-transmitted infection.
AB  - A probabilistic model was used to compare cryoprecipitate to viral inactivated,
      commercial fibrinogen concentrate to evaluate with regard to the recipient's risk
      of exposure to an emergent AIDS-like epidemic. In patients who occasionally need
      a therapeutic dose of fibrinogen, commercial fibrinogen would be marginally safer
      than cryoprecipitate if the new pathogen were sensitive to inactivation. But
      there is a potential high risk of exposure if the emerging agent withstands
      inactivation. In most of the analyzed scenarios, cryoprecipitate is safer than
      commercial fibrinogen as long as the odds that the new agent is sensitive to
      inactivation are lower than 1.000 to 1.

PMID- 17550861
TI  - Quantification by magnetic resonance imaging and liver consequences of post
      transfusional iron overload alone in long term survivors after allogeneic
      hematopoietic stem cell transplantation (HSCT).
AB  - We quantified and studied the impact of post transfusional iron overload alone in
      post allogeneic HSCT. Median number of RBCs was 18. Ferritin was 532 mg/L. Liver
      iron content (LIC) was 117 mmoles/gdw. Correlation RBCs and ferritin was
      (r=0.81); RBCs and LIC was (r=0.84). The high ferritin group differed from normal
      ferritin group in terms of RBCs transfused (p<10(-3)), ALT (p<0.009). But
      occurrence of liver dysfunction was not significant. Magnitude of iron overload
      correlates closely to the number of RBCs and is quantified by MRI. Impact on
      liver dysfunction is moderate in absence of co-morbidity.

PMID- 17550862
TI  - Effectiveness of a dedicated day hospital for management of acute sickle cell
      pain.
AB  - Severe acute pain is common in sickle cell disease (SCD). Increasingly
      overburdened emergency departments are not the most appropriate setting in which
      to manage pain that requires close monitoring and careful opioid dose titration.1
      We report on the benefit of treating acute pain in SCD in a day hospital (DH).

PMID- 17550863
TI  - Aberrant positivity for CD79a in erythroid lineage cells--a finding observed in a
      subset of re-staging bone marrow trephine biopsies after treatment cell pain.
AB  - Aberrant expression of CD79a has been reported in neoplastic cells in peripheral
      T cell lymphoma, T-cell acute lymphoblastic leukemia and acute myeloid leukemia
      (especially those with t(8;21)). In this report, we document the first report of
      CD79a positivity in erythroid precursor cells in bone marrow. In all, we document
      this finding in five of 18 re-staging bone marrow trephine samples in patients of
      lymphoma treated with chemotherapy (one index case and 17 additional validation
      cases). It is important to appreciate this finding especially in rituximab
      treated patients where one tends to rely on CD79a to identify minimal marrow
      disease.

PMID- 17550864
TI  - Anti-interleukin 6 receptor antibody tocilizumab reduces the level of serum
      hepcidin in patients with multicentric Castleman's disease.
AB  - We report two cases of multicentric Castleman's disease (MCD) whose serum
      hepcidin levels were rapidly down-regulated by administration of tocilizumab, an
      anti- interleukin 6 (IL-6) receptor antibody. Our results indicate that IL-6
      induced hepcidin over-production may be involved in the pathophysiology of
      microcytic anemia commonly observed in this disease.

PMID- 17550865
TI  - A simple method for detection of major phenotypic abnormalities in
      myelodysplastic syndromes: expression of CD56 in CMML.
AB  - Using a very simple flow cytometry protocol, we found that CD36 and CD117 on
      granulocytes and CD56 on monocytes were the major bone marrow phenotypic
      aberrations in patients with myelodysplasia, including CMML. CD56 on monocytes
      was associated with CMML. Importantly, phenotypic aberrations were lost on blood
      cells, except for CD56.

PMID- 17550866
TI  - AML1 mutation and its coexistence with different transcription factor gene
      families in de novo acute myeloid leukemia (AML): redundancy or synergism.
AB  - AML1 mutations were identified in 6.3% of AML patients with chromosomal
      translocations involving CBF, PML-RARalpha, HOX, or ETS transcription factor (TF)
      gene families. Rare chromosomal abnormalities, t(16;21) and t(7;11), were also
      found. This study represents the first series to demonstrate the coexistence of
      known and novel AML1 mutations with different TF gene mutations. Although the
      occurrence of two TF gene mutations may appear unnecessary, the possible
      synergistic mechanism between different TF gene families cannot be excluded and
      needs to be further explored.

PMID- 17550867
TI  - Deregulated over expression of FOXP1 protein in diffuse large B-cell lymphoma
      does not occur as a result of gene rearrangement.
AB  - Strong uniform expression of FOXP1 protein occurs in a subgroup of non-germinal
      centre (GC) diffuse large B-cell lymphomas (DLBCL). We have investigated gene
      rearrangement as a potential mechanism for deregulated expression of FOXP1
      however, using FISH FOXP1 translocations were not found in any case with over
      expression of the protein.

PMID- 17550868
TI  - The relationship between the sense of self-agency and schizotypal personality
      traits.
AB  - People with schizotypal traits may possess abnormal self-awareness, particularly
      with regard to their sense of self-agency, that is, the sense that it is oneself
      who is causing or generating an action. Participants in Experiments 1A (N = 11),
      1B (N = 12), and 2 (N = 20) moved a mouse device and viewed resultant feedback,
      which was biased either temporally or spatially. They then judged whether there
      was a bias or whether they felt they had moved the cursor on their own. The
      authors found, for the 1st time, that a sense of self-agency can be experienced
      even if some degree of temporal bias is perceived. Furthermore, they determined
      that highly schizotypal people have an abnormal (weaker) sense of self-agency.

PMID- 17550869
TI  - Visuomotor memory for target location in near and far reaching spaces.
AB  - The authors investigated systematic error associated with endpoints of memory
      guided actions performed in near and far reaching spaces. To accomplish that
      objective, the authors instructed 12 participants to initiate open-loop and
      memory-guided reaches (0, 2,000, and 5,000 ms of visual delay) from a common
      start position to remembered midline targets in near (i.e., a backward reach) and
      far (i.e., a forward reach) reaching spaces. The results indicated that near and
      far reaches, respectively, over- and undershot veridical target location, and the
      direction-specific nature of the error was amplified in the memory-guided
      conditions. The latter finding represents an important aspect of the present
      research because it suggests that the direction-specific error identified here is
      related to factors arising within the sensory component of the task rather than
      mechanical differences in reaching direction. The authors propose that stored
      target information serving memory guided actions is susceptible to a compression
      of visual space in memory such that the egocentric distance of a remembered
      target is underestimated.

PMID- 17550870
TI  - Visual and haptic feedback contribute to tuning and online control during object
      manipulation.
AB  - The authors employed a virtual environment to investigate how humans use haptic
      and visual feedback in a simple, rhythmic object-manipulation task. The authors
      hypothesized that feedback would help participants identify the appropriate
      resonant frequency and perform online control adjustments. The 1st test was
      whether sensory feedback is needed at all; the 2nd was whether the motor system
      combines visual and haptic feedback to improve performance. Task performance was
      quantified in terms of work performed on the virtual inertia, ability to identify
      the correct rhythm, and variability of movement. Strict feedforward control was
      found to be ineffective for this task, even when participants had previous
      knowledge of the rhythm. Participants (N = 11) performed far better when feedback
      was available (11 times more work, 2.2 times more precise frequency, 30% less
      variability; p < .05 for all 3 performance measures). Using sensory feedback,
      participants were able to rapidly identify 4 different spring-inertia systems
      without foreknowledge of the corresponding resonant frequencies. They performed
      over 20% more work with 24% less variability when provided with both visual and
      haptic feedback than they did with either feedback channel alone (p < .05),
      providing evidence that they integrated online sensory channels. Whereas
      feedforward control alone led to poor performance, feedback control led to fast
      tuning or calibration of control according to the resonant frequency of the
      object, and to better control of the rhythmic movement itself.

PMID- 17550871
TI  - Quadriceps EMG in open and closed kinetic chain tasks in women with
      patellofemoral pain.
AB  - The authors investigated whether the discrepancy noted in the literature
      regarding delayed and decreased activity in vastus medialis obliquus (VMO) in
      people with patellofemoral pain (PFP) depends on the nature of the open kinetic
      chain (OKC) and the closed kinetic chain (CKC) in the experimental task. They
      hypothesized that activity in VMO would be more delayed and decreased in CKC
      tasks than in OKC tasks. Women with PFP (n = 17) and healthy controls (n = 17)
      performed isometric quadriceps contractions in CKC and OKC tasks. The authors
      manipulated only the application of resistance. Electromyographs (EMGs) showed
      that participants with PFP reacted later and activated the quadriceps more in the
      CKC task but had intramuscular quadriceps coordination similar to that of
      controls. The nature of the OKC task or the CKC task does not seem to explain
      contradictory findings regarding VMO activation.

PMID- 17550872
TI  - A dynamical systems analysis of spontaneous movements in newborn infants.
AB  - The authors evaluated the characteristics of infants' spontaneous movements by
      using dynamical systems analysis. Participants were 6 healthy 1-month-old full
      term newborn infants (3 males, 3 females). They used a triaxial accelerometer to
      measure limb acceleration in 3-dimensional space. Acceleration signals were
      recorded during 200 s from the right wrist when the infant was in an active alert
      state and lying supine (sampling rate 200 Hz). and was stored in the system's
      memory. Digitized data were transferred to a PC for subsequent processing with
      analysis software. The acceleration time series data were analyzed linearly and
      nonlinearly. Nonlinear time series analysis suggested that the infants'
      spontaneous movements are characterized by a nonlinear chaotic dynamics with 5 or
      6 embedding dimensions. The production of infants'spontaneous movements involves
      chaotic dynamic systems that are capable of generating voluntary skill movements.

PMID- 17550873
TI  - Posture control and complex arm coordination: analysis of multijoint coordinative
      movements and stability of stance.
AB  - The authors addressed the interactions between control of bimanual multijoint
      coordination tasks and posture. Participants (N = 6) performed 8 coordination
      patterns that differed in degree of complexity by using their bilateral elbows
      and wrists under 3 scaled motion speeds while standing on 2 force plates. Results
      indicated that producing complex bimanual multijoint coordinative tasks affected
      postural sway, thus resulting in an increase of sway activity. Behavioral as well
      as mechanical factors accounted for the increased disturbance in postural sway.
      Those findings suggest that performing complex coordination tasks disrupts
      postural control in normal young adults.

PMID- 17550874
TI  - Changes in mechanical control of movement during the first 5 months of
      independent walking: a longitudinal study.
AB  - Insight into neuromuscular control of movement is gained through an understanding
      of the mechanical causes of movement. Data on new walkers' net joint moments is
      scarce, however, although those moments can be considered the direct cause of
      movement. The authors' goal in this research project was to characterize net
      joint moments in toddlers (N = 10) during the first 5 months of independent
      walking and to discuss their role in mechanical control of walking. The authors
      modeled leg segments as oscillating pendulums fixed at the proximal joint and
      investigated the relationship between force and movement. Their investigation
      revealed that at the onset of independent gait, walking was primarily hip driven.
      Furthermore, the toddlers seemed to experience problems in uncoupling active and
      passive control around the joints. Changes in mechanical control of walking were
      observed after 3 to 4 months of independent walking. The changes were more
      obvious at the hip and the knee joint than at the ankle.

PMID- 17550875
TI  - Fitness increases with partner and neighbour allopreening.
AB  - Altruism and selfishness are fundamental characteristics of human and animal
      societies. Among colonial biparental species, breeding outcome depends on
      interactions between mates and neighbours. However, the relationships between
      cooperation within and among partnerships and fitness have not been fully
      investigated. We show that in the highly colonial common guillemot (Uria aalge),
      altruistic behaviour (allopreening) towards a mate was positively related to long
      term fitness, whereas allopreening a neighbour was related to current fitness.
      Turnover is much lower within than between pairs, so our results suggest that
      allopreening within pairs generates fitness returns at longer timescales than
      between pairs. Allopreening not only removes ectoparasites and maintains plumage
      condition, but may also have important social functions. We found a negative
      relationship between fight rate and allopreen rate between breeding neighbours,
      with nests exhibiting low breeding success having a higher frequency of fights
      with neighbours. We also found evidence for reciprocity in allopreening. Thus,
      allopreening may function as a reciprocal stress reducer, to decrease the
      likelihood of fights and associated breeding failure. We suggest that altruistic
      behaviour has long-term benefits for the survival of the offspring when living in
      a crowded neighbourhood.

PMID- 17550876
TI  - Female red deer prefer the roars of larger males.
AB  - Surprisingly little is known about the role of acoustic cues in mammal female
      mate choice. Here, we examine the response of female red deer (Cervus elaphus) to
      male roars in which an acoustic cue to body size, the formants, has been re
      scaled to simulate different size callers. Our results show that oestrous red
      deer hinds prefer roars simulating larger callers and constitute the first
      evidence that female mammals use an acoustic cue to body size in a mate choice
      context. We go on to suggest that sexual selection through female mating
      preferences may have provided an additional selection pressure along with male
      male competition for broadcasting size-related information in red deer and other
      mammals.

PMID- 17550877
TI  - Do carotenoids buffer testosterone-induced immunosuppression? An experimental
      test in a colourful songbird.
AB  - Testosterone (T) is hypothesized to be an important honesty reinforcer of animal
      sexual signals. Owing to its immunosuppressive effects, only those individuals
      that can immunologically withstand high T levels can develop the most exaggerated
      traits. To date, few studies have isolated phenotypic or genotypic buffers that
      provide 'high-quality' animals with such an advantage. Dietary carotenoid
      pigments may in fact confer such a benefit because when in high supply
      carotenoids boost immunocompetence and coloration in animals like birds and
      fishes. We examined the experimental effect of T elevation on carotenoid and
      immune status in male and female zebra finches (Taeniopygia guttata) and found
      that T was immunostimulatory in a generalized cell-mediated challenge. We also
      detected a significant interaction between T treatment and the change in plasma
      carotenoids that occurred during the immune challenge; the relationship between
      blood carotenoid change and immunity was positive in controls and negative in T
      implanted birds. This suggests that, while correlationally birds with high
      carotenoid stores were inherently better at mounting strong immune responses,
      experimentally administered T induced birds to deplete carotenoids for maximizing
      their health. Our findings highlight a nutrient-specific mechanism by which
      animals escape high immune costs of T elevation and thus can still elevate
      ornamentation.

PMID- 17550878
TI  - The uniquely human capacity to throw evolved from a non-throwing primate: an
      evolutionary dissociation between action and perception.
AB  - Humans are uniquely endowed with the ability to engage in accurate, high-momentum
      throwing. Underlying this ability is a unique morphological adaptation that
      enables the characteristic rotation of the arm and pelvis. What is unknown is
      whether the psychological mechanisms that accompany the act of throwing are also
      uniquely human. Here we explore this problem by asking whether free-ranging
      rhesus monkeys (Macaca mulatta), which lack both the morphological and neural
      structures to throw, nonetheless recognize the functional properties of throwing.
      Rhesus not only understand that human throwing represents a threat, but that some
      aspects of a throwing event are more relevant than others; specifically, rhesus
      are sensitive to the kinematics, direction and speed of the rotating arm, the
      direction of the thrower's eye gaze and the object thrown. These results suggest
      that the capacity to throw did not coevolve with psychological mechanisms that
      accompany throwing; rather, this capacity may have built upon pre-existing
      perceptual processes. These results are consistent with a growing body of work
      showing that non-human animals often exhibit perceptual competencies that do not
      show up in their motor responses, suggesting evolutionary dissociations between
      the systems of perception that provide understanding of the world and those that
      mediate action on the world.

PMID- 17550879
TI  - Colour preferences and colour vision in poultry chicks.
AB  - The dramatic colours of biological communication signals raise questions about
      how animals perceive suprathreshold colour differences, and there are long
      standing questions about colour preferences and colour categorization by non
      human species. This study investigates preferences of foraging poultry chicks
      (Gallus gallus) as they peck at coloured objects. Work on colour recognition
      often deals with responses to monochromatic lights and how animals divide the
      spectrum. We used complementary colours, where the intermediate is grey, and
      related the chicks' choices to three models of the factors that may affect the
      attractiveness. Two models assume that attractiveness is determined by a metric
      based on the colour discrimination threshold either (i) by chromatic contrast
      against the background or (ii) relative to an internal standard. An alternative
      third model is that categorization is important. We tested newly hatched and 9
      day-old chicks with four pairs of (avian) complementary colours, which were
      orange, blue, red and green for humans. Chromatic contrast was more relevant to
      newly hatched chicks than to 9-day-old birds, but in neither case could contrast
      alone account for preferences; especially for orange over blue. For older chicks,
      there is evidence for categorization of complementary colours, with a boundary at
      grey.

PMID- 17550880
TI  - The key mimetic features of hoverflies through avian eyes.
AB  - Batesian mimicry occurs when a palatable species (the mimic) gains protection
      from predators by resembling an unpalatable or otherwise protected species (the
      model). While some mimetic species resemble their models closely, other species
      ('imperfect mimics') are thought to bear only a crude likeness. In an earlier
      study, pigeons (Columba livia) were trained to recognize wasp images in one
      experiment and non-mimetic (NM) fly images in another by rewarding the pigeons
      for pecking on the respective image types. These pigeons were subsequently
      presented with different images, including seemingly wasp-like hoverfly species,
      and the recorded peck rates on these images were used as a measure of the
      pigeons' perception of the hoverflies' mimetic similarity. To identify a
      candidate set of morphological features that the pigeons used when assessing this
      mimetic similarity, we first extracted a range of biometrical measurements from
      images originally presented to the pigeons. We then repeatedly optimized an
      empirical model in an attempt to match the recorded pigeon peck rates while using
      as few biometrical features as input as possible. Our models were able to fit the
      pigeon peck rates with considerable accuracy even while excluding many input
      features. Antennal length, a feature commonly used to discriminate between flies
      and wasps, was regularly retained as an input variable, but overall a different
      set of biometrical features was important for predicting the peck rates of
      pigeons rewarded for identifying wasps compared to those rewarded for identifying
      NM flies. In highlighting the importance of specific biometrical features in
      promoting mimicry and the irrelevance of others, our optimized models provide an
      explanation as to why certain species that appear to be poor mimics to humans are
      judged to be good mimics by birds.

PMID- 17550881
TI  - Low host-pathogen specificity in the leaf-cutting ant-microbe symbiosis.
AB  - Host-parasite associations are shaped by coevolutionary dynamics. One example is
      the complex fungus-growing ant-microbe symbiosis, which includes ancient host
      parasite coevolution. Fungus-growing ants and the fungi they cultivate for food
      have an antagonistic symbiosis with Escovopsis, a specialized microfungus that
      infects the ants' fungus gardens. The evolutionary histories of the ant, cultivar
      and Escovopsis are highly congruent at the deepest phylogenetic levels, with
      specific parasite lineages exclusively associating with corresponding groups of
      ants and cultivar. Here, we examine host-parasite specificity at finer
      phylogenetic levels, within the most derived clade of fungus-growing ants, the
      leaf-cutters (Atta spp. and Acromyrmex spp.). Our molecular phylogeny of
      Escovopsis isolates from the leaf-cutter ant-microbe symbiosis confirms
      specificity at the broad phylogenetic level, but reveals frequent host-switching
      events between species and genera of leaf-cutter ants. Escovopsis strains
      isolated from Acromyrmex and Atta gardens occur together in the same clades, and
      very closely related strains can even infect the gardens of both ant genera.
      Experimental evidence supports low host-parasite specificity, with
      phylogenetically diverse strains of Escovopsis being capable of overgrowing all
      leaf-cutter cultivars examined. Thus, our findings indicate that this host
      pathogen association is shaped by the farming ants having to protect their
      cultivated fungus from phylogenetically diverse Escovopsis garden pathogens.

PMID- 17550882
TI  - An experimental test of frequency-dependent selection on male mating strategy in
      the field.
AB  - We provide field-based experimental evidence for the frequency-dependent nature
      of the fitness of alternative mating strategies. We manipulated the frequency of
      genetically determined phenotypic strategies in six wild populations of the side
      blotched lizard, Uta stansburiana. The within-population pattern of mating was
      assessed using nine microsatellite loci to assign paternity. Within populations
      of the side-blotched lizard exist three colour morphs (orange, blue and yellow)
      associated with male mating strategy. The frequency of these morphs has
      previously been found to oscillate over a 4- to 5-year period. We found, as
      predicted, that the common phenotype lost fitness to its antagonist. The mating
      patterns of all six populations adhered to a priori predictions that were derived
      from previous empirical and theoretical observations on this system. We found
      that the frequency-dependent nature of male fitness could be accounted for by the
      composition of their competitors at a small local population level, driven by
      associations within a focal female's social neighbourhood.

PMID- 17550883
TI  - The age and evolution of an antiviral resistance mutation in Drosophila
      melanogaster.
AB  - What selective processes underlie the evolution of parasites and their hosts?
      Arms-race models propose that new host-resistance mutations or parasite counter
      adaptations arise and sweep to fixation. Frequency-dependent models propose that
      selection favours pathogens adapted to the most common host genotypes, conferring
      an advantage to rare host genotypes. Distinguishing between these models is
      empirically difficult. The maintenance of disease-resistance polymorphisms has
      been studied in detail in plants, but less so in animals, and rarely in natural
      populations. We have made a detailed study of genetic variation in host
      resistance in a natural animal population, Drosophila melanogaster, and its
      natural pathogen, the sigma virus. We confirm previous findings that a single
      (albeit complex) mutation in the gene ref(2)P confers resistance against sigma
      and show that this mutation has increased in frequency under positive selection.
      Previous studies suggested that ref(2)P polymorphism reflects the progress of a
      very recent selective sweep, and that in Europe during the 1980s, this was
      followed by a sweep of a sigma virus strain able to infect flies carrying this
      mutation. We find that the ref(2)P resistance mutation is considerably older than
      the recent spread of this viral strain and suggest that--possibly because it is
      recessive--the initial spread of the resistance mutation was very slow.

PMID- 17550884
TI  - Climatically driven synchrony of gerbil populations allows large-scale plague
      outbreaks.
AB  - In central Asia, the great gerbil (Rhombomys opimus) is the main host for the
      bacterium Yersinia pestis, the cause of bubonic plague. In order to prevent
      plague outbreaks, monitoring of the great gerbil has been carried out in
      Kazakhstan since the late 1940s. We use the resulting data to demonstrate that
      climate forcing synchronizes the dynamics of gerbils over large geographical
      areas. As it is known that gerbil densities need to exceed a threshold level for
      plague to persist, synchrony in gerbil abundance across large geographical areas
      is likely to be a condition for plague outbreaks at similar large scales. Here,
      we substantiate this proposition through autoregressive modelling involving the
      normalized differentiated vegetation index as a forcing covariate. Based upon
      predicted climate changes, our study suggests that during the next century,
      plague epizootics may become more frequent in central Asia.

PMID- 17550885
TI  - The interfacial structure and Young's modulus of peptide films having switchable
      mechanical properties.
AB  - We report the structure and Young's modulus of switchable films formed by peptide
      self-assembly at the air-water interface. Peptide surfactant AM1 forms an
      interfacial film that can be switched, reversibly, from a high- to low-elasticity
      state, with rapid loss of emulsion and foam stability. Using neutron
      reflectometry, we find that the AM1 film comprises a thin (approx. 15A) layer of
      ordered peptide in both states, confirming that it is possible to drastically
      alter the mechanical properties of an interfacial ensemble without significantly
      altering its concentration or macromolecular organization. We also report the
      first experimentally determined Young's modulus of a peptide film self-assembled
      at the air-water interface (E=80MPa for AM1, switching to E<20MPa). These
      findings suggest a fundamental link between E and the macroscopic stability of
      peptide-containing foam. Finally, we report studies of a designed peptide
      surfactant, Lac21E, which we find forms a stronger switchable film than AM1
      (E=335MPa switching to E<4MPa). In contrast to AM1, Lac21E switching is caused by
      peptide dissociation from the interface (i.e. by self-disassembly). This research
      confirms that small changes in molecular design can lead to similar macroscopic
      behaviour via surprisingly different mechanisms.

PMID- 17550886
TI  - Antimicrobial use in Finnish acute care hospitals: data from national prevalence
      survey, 2005.
AB  - OBJECTIVES: In Finland, use of antimicrobials in ambulatory care is moderate, but
      some reports suggest that hospital use is higher than in other European
      countries. We evaluated the amount and type of antimicrobials administered in
      Finnish acute care hospitals. PATIENTS AND METHODS: We analysed data collected in
      the national prevalence survey of nosocomial infections (NIs) during February
      March 2005 in all tertiary care, all secondary care and 25% of other acute care
      hospitals. All inpatients present on the study day in acute care wards for adults
      were included (n=8234). The names and use-days of antimicrobials in Anatomical
      Therapeutic Class groups J01-J05 were collected on the study day and
      retrospectively for the previous 6 days. RESULTS: On the study day, 39% of
      patients had received at least one, 14% at least two and 3% at least three
      antimicrobials; patients with NI represented 21%, 29% and 45% of these groups,
      respectively. The prevalence of patients receiving any antimicrobial was 53% in
      intensive care patients and varied in other specialties from 0% in ophthalmology
      to 63% in dental and oral surgery. Within a 7 day period, the total use of
      antibacterial agents (J01) was 64 use-days per 100 patient-days. Cephalosporins
      were the most frequently used antimicrobials, followed by quinolones and
      metronidazole. CONCLUSIONS: The prevalence and spectrum of antimicrobial use in
      Finnish acute care hospitals were high. NI patients contributed markedly to the
      total usage. The NI survey with a 7 day data collection period provided insights
      into the use-density of antimicrobials.

PMID- 17550887
TI  - Detection of HSV-1 variants highly resistant to the helicase-primase inhibitor
      BAY 57-1293 at high frequency in 2 of 10 recent clinical isolates of HSV-1.
AB  - OBJECTIVES: BAY 57-1293 is a helicase-primase inhibitor (HPI) from a new class of
      antivirals that are highly efficacious in herpes simplex virus (HSV)-1 animal
      infection models. Resistant mutants with point mutations in the helicase (UL5)
      were reported to be present in laboratory isolates at a low frequency of
      approximately 10(-6). In contrast, we have shown elsewhere that some laboratory
      isolates contain resistant variants at higher frequency (10(-4)). Therefore, we
      screened 10 recent clinical isolates of HSV-1 for BAY 57-1293-resistant virions.
      METHODS: Clinical isolates were screened by a plaque reduction assay in Vero
      cells to determine the frequency of occurrence of BAY 57-1293-resistant variants.
      The helicase gene for the resistant variants was sequenced. RESULTS: One isolate
      contained highly resistant variants at 10(-4) and another at 10(-5). Both
      variants contained a previously reported BAY 57-1293 resistance mutation (K356N)
      in UL5 and were >5000-fold resistant. CONCLUSIONS: Occurrence of HPI-resistant
      viruses at high frequency in a clinical isolate is intriguing. Two alternative
      hypotheses are proposed to explain this phenomenon. It is also surprising that
      two unrelated clinical isolates contain an identical HPI resistance mutation.
      These results have important implications for HPI drug-resistance monitoring
      during subsequent clinical trials.

PMID- 17550888
TI  - Comment on: the increasing use of silver-based products as antimicrobial agents:
      a useful development or a cause for concern?

PMID- 17550889
TI  - Daptomycin for endocarditis and/or bacteraemia: a systematic review of the
      experimental and clinical evidence.
AB  - BACKGROUND: Endocarditis and bacteraemia are devastating infections with high
      mortality. Gram-positive cocci are the most commonly isolated pathogens. In an
      era of multidrug-resistant pathogens, the evaluation of new treatment options is
      important. Daptomycin is a cyclic lipopeptide that is active against most of
      these pathogens. Furthermore, it is a bactericidal antibiotic, a factor that is
      frequently considered in the choice of treatment of patients with bacteraemia and
      endocarditis. METHODS: We performed a systematic review of the evidence for the
      effectiveness of daptomycin in the treatment of patients and animals with
      endocarditis and/or bacteraemia. We searched PubMed and Scopus databases for
      relevant studies. Case reports, case series, controlled trials, randomized
      controlled trials and comparative studies using experimental animal models were
      included. RESULTS: The most reliable information comes from the single
      multicentre randomized controlled trial conducted on this issue, which showed
      that daptomycin is a promising antibiotic for the treatment of patients with
      Staphylococcus aureus bacteraemia and endocarditis. The experimental models
      indicate that the combination of daptomycin with rifampicin or gentamicin can
      improve outcomes further. Finally, in several of the published relevant case
      reports daptomycin was administered in patients with haematological malignancies.
      CONCLUSIONS: Daptomycin is a promising antibiotic that has been already approved
      for the treatment of patients with right-sided endocarditis and bacteraemia.
      However, the available clinical evidence is limited and further evaluation of the
      antibiotic is warranted. The commonly reported de novo development of resistance
      is a major concern that may limit its use. More controlled trials are needed,
      especially for patients infected with multidrug-resistant Gram-positive cocci,
      comparing daptomycin with other available treatment options, including
      glycopeptides and oxazolidinones.

PMID- 17550890
TI  - Identification of individual structural fragments of N,N'-(bis-5
      nitropyrimidyl)dispirotripiperazine derivatives for cytotoxicity and antiherpetic
      activity allows the prediction of new highly active compounds.
AB  - OBJECTIVES: The objectives of this study were (i) to apply computer-based
      technologies to evaluate the structure of 48 N,N'-(bis-5
      nitropyrimidyl)dispirotripiperazines which belong to a new class of highly active
      antiviral compounds binding to cell surface heparan sulphates, (ii) to understand
      the chemical- biological interactions governing their activities, and (iii) to
      design new compounds with strong antiviral activity. METHODS: The logarithm of
      50% cytotoxic concentration (CC(50)) in GMK cells, of 50% inhibitory
      concentration (IC(50)) against herpes simplex virus type 1, and of selectivity
      index (SI = CC(50)/IC(50)) was used to develop quantitative structure-activity
      relationships (QSARs) based on simplex representation of molecular structure. The
      QSAR model was applied to design new compounds. Two of these compounds were
      synthesized, physico-chemically characterized and tested for cytotoxicity and
      antiviral activity. RESULTS: Statistic characteristics for partial least squares
      models allow the prediction of CC(50), IC(50) and SI values. The QSAR results
      demonstrate a high impact of individual structural fragments for antiviral
      activity. Molecular fragments that promote and interfere with antiviral activity
      were defined on the basis of the obtained models. Electrostatic factors (38%) and
      hydrophobicity (34%) were the most important determinants of antiherpetic
      activity. Using the established method, new potential dispirotripiperazine
      derivatives were computationally designed. Two of these computationally designed
      compounds were synthesized. The biological test results confirm the
      computationally predicted values of these compounds. CONCLUSIONS: The established
      QSAR model is suitable for the design of new antiherpetic compounds and
      prediction of their activity.

PMID- 17550891
TI  - Temocillin susceptibility by BSAC methodology.

PMID- 17550892
TI  - Counterfeit or substandard antimicrobial drugs: a review of the scientific
      evidence.
AB  - There is growing universal concern regarding counterfeit medications. In
      particular, counterfeit antimicrobial drugs are a threat to public health with
      many devastating consequences for patients; increased mortality and morbidity and
      emergence of drug resistance. In addition, physicians treating these patients
      lose their confidence in the medications used and report high levels of bacterial
      resistance. The problem with fake and suboptimal medications got worse with the
      advent of the World Wide Web; a significant proportion of medications that are
      sold through Internet pharmacies is counterfeit. Various initiatives of the WHO
      (the International Medical Products Anti-Counterfeiting Taskforce) are hopefully
      going to tackle this very important public health issue. In this article, we
      review the available evidence in peer-reviewed articles and World Wide Web
      information resources regarding the issue of counterfeit antimicrobials.

PMID- 17550893
TI  - Glycomics analysis of Schistosoma mansoni egg and cercarial secretions.
AB  - The parasitic helminth Schistosoma mansoni is a major public health concern in
      many developing countries. Glycoconjugates, and in particular the carbohydrate
      component of these products, represent the main immunogenic challenge to the host
      and could therefore represent one of the crucial determinants for successful
      parasite establishment. Here we report a comparative glycomics analysis of the N-
      and O-glycans derived from glycoproteins present in S. mansoni egg (egg-secreted
      protein) and cercarial (0-3-h released protein) secretions by a combination of
      mass spectrometric techniques. Our results show that S. mansoni secrete
      glycoproteins with glycosylation patterns that are complex and stage-specific.
      Cercarial stage secretions were dominated by N-glycans that were core
      xylosylated, whereas N-glycans from egg secretions were predominantly core
      difucosylated. O-Glycan core structures from cercarial secretions primarily
      consisted of the core sequence Galbeta1-->3(Galbeta1-->6)GalNAc, whereas egg
      secreted O-glycans carried the mucin-type core 1 (Galbeta1-->3GalNAc) and 2
      (Galbeta1-->3(GlcNAcbeta1-->6)GalNAc) structures. Additionally we identified a
      novel O-glycan core in both secretions in which a Gal residue is linked to the
      protein. Terminal structures of N- and O-glycans contained high levels of fucose
      and include stage-specific structures. These glycan structures identified in S.
      mansoni secretions are potentially antigenic motifs and ligands for carbohydrate
      binding proteins of the host immune system.

PMID- 17550894
TI  - NMR shows hydrophobic interactions replace glycine packing in the triple helix at
      a natural break in the (Gly-X-Y)n repeat.
AB  - Little is known about the structural consequences of the more than 20 breaks in
      the (Gly-X-Y)(n) repeating sequence found in the long triple helix domain of
      basement membrane type IV collagen. NMR triple resonance studies of doubly
      labeled residues within a set of collagen model peptides provide distance and
      dihedral angle restraints that allow determination of model structures of both a
      standard triple helix and of a triple helix with a break in solution. Although
      the standard triple helix cannot continue when Gly is not every third residue,
      the NMR data support rod-like molecules that have standard triple-helical
      structures on both sides of a well defined and highly localized perturbation. The
      GAAVM break region may be described as a "pseudo triple helix," because it
      preserves the standard one-residue stagger of the triple helix but introduces
      hydrophobic interactions at the position normally occupied by the much smaller
      and hydrogen-bonded Gly residue of the repeating (Gly-X-Y)(n) sequence. This
      structure provides a rationale for the consensus presence of hydrophobic residues
      in breaks of similar length and defines a novel variant of a triple helix that
      could be involved in recognition.

PMID- 17550895
TI  - AtCCMA interacts with AtCcmB to form a novel mitochondrial ABC transporter
      involved in cytochrome c maturation in Arabidopsis.
AB  - ABC transporters make a large and diverse family of proteins found in all phylae.
      AtCCMA is the nucleotide binding domain of a novel Arabidopsis mitochondrial ABC
      transporter. It is encoded in the nucleus and imported into mitochondria. Sub
      organellar and topology studies find AtCCMA bound to the mitochondrial inner
      membrane, facing the matrix. AtCCMA exhibits an ATPase activity, and ATP/Mg(2+)
      can facilitate its dissociation from membranes. Blue Native PAGE shows that it is
      part of a 480-kDa complex. Yeast two-hybrid assays reveal interactions between
      AtCCMA and domains of CcmB, the mitochondria-encoded transmembrane protein of a
      conserved ABC transporter. All these properties designate the protein as the
      ortholog in plant mitochondria of the bacterial CcmA required for cytochrome c
      maturation. The transporter that involves AtCCMA defines a new category of
      eukaryotic ABC proteins because its transmembrane and nucleotide binding domains
      are encoded by separate genomes.

PMID- 17550896
TI  - The fission yeast Jmj2 reverses histone H3 Lysine 4 trimethylation.
AB  - Histone methylation regulates transcription, chromatin structure, and the
      epigenetic state of the cell. Recent studies identified the JmjC domain as a
      catalytic module for histone demethylation. Schizosaccharomyces pombe contains
      seven JmjC proteins, but it was unclear whether any of them functioned as histone
      demethylases. In this report, we show that the JmjC protein Jmj2, which is
      evolutionarily conserved from yeast to human, reversed trimethylated H3-Lys-4 to
      di- and mono-but not unmethylated products. Overexpression of Jmj2 but not a
      catalytically inactive mutant reduced H3-Lys-4 trimethylation levels in vivo and
      suppressed the toxicity caused by overexpression of the H3-Lys-4-me3-binding
      protein Yng1 in budding yeast. Genome-wide analysis showed that the loss of jmj2
      was associated with an increase in the H3-Lys-4-me3 signal, which was enriched
      near the transcriptional start sites and the coding regions. At the mating-type
      locus, the loss of jmj2 or substitution of jmj2 with a catalytically inactive
      form is correlated with increased reporter gene transcription and H3-Lys-4-me3/2
      levels, suggesting that Jmj2 and its demethylase activity may play a role in
      heterochromatin biology. Our findings identified a novel S. pombe histone
      demethylase with specificity toward di- and trimethylated histone H3-Lys-4 and a
      possible role in heterochromatin regulation.

PMID- 17550897
TI  - The calponin homology domain of Vav1 associates with calmodulin and is
      prerequisite to T cell antigen receptor-induced calcium release in Jurkat T
      lymphocytes.
AB  - Vav1 is a guanine nucleotide exchange factor that is expressed specifically in
      hematopoietic cells and plays important roles in T cell development and
      activation. Vav1 consists of multiple structural domains so as to facilitate both
      its guanine nucleotide exchange activity and scaffold function following T cell
      antigen receptor (TCR) engagement. Previous studies demonstrated that the
      calponin homology (CH) domain of Vav1 is required for TCR-stimulated calcium
      mobilization and thus downstream activation of nuclear factor of activated T
      cells. However, it remained obscure how Vav1 functions in regulating calcium
      flux. In an effort to explore molecules interacting with Vav1, we found that
      calmodulin bound to Vav1 in a calcium-dependent and TCR activation-independent
      manner. The binding site was mapped to the CH domain of Vav1. Reconstitution of
      vav1-null Jurkat T cells (J.Vav1) with CH-deleted Vav1 exhibited a severe
      deficiency in calcium release to the same extent as that of Jurkat cells treated
      with the calmodulin inhibitor or J.Vav1 cells. The defect persisted even when
      phospholipase-Cgamma1 was fully activated, indicating a prerequisite role of Vav1
      CH domain in calcium signaling. The results suggest that Vav1 and calmodulin
      function cooperatively to potentiate TCR-induced calcium release. This study
      unveiled a mechanism by which the Vav1 CH domain is involved in calcium signaling
      and provides insight into our understanding of the role of Vav1 in T cell
      activation.

PMID- 17550898
TI  - A conserved cysteine is essential for Pex4p-dependent ubiquitination of the
      peroxisomal import receptor Pex5p.
AB  - The peroxisomal protein import receptor Pex5p is modified by ubiquitin, both in
      an Ubc4p-dependent and -independent manner. Here we show that the two types of
      ubiquitination target different residues in the NH(2)-terminal region of Pex5p
      and we identify Pex4p (Ubc10p) as the ubiquitin-conjugating enzyme required for
      Ubc4p-independent ubiquitination. Whereas Ubc4p-dependent ubiquitination occurs
      on two lysine residues, Pex4p-dependent ubiquitination neither requires lysine
      residues nor the NH(2)-terminal alpha-NH(2) group. Instead, a conserved cysteine
      residue appears to be essential for both the Pex4p-dependent ubiquitination and
      the overall function of Pex5p. In addition, we show that this form of
      ubiquitinated Pex5p is susceptible to the reducing agent beta-mercaptoethanol, a
      compound that is unable to break ubiquitin-NH(2) group linkages. Together, our
      results strongly suggest that Pex4p-dependent ubiquitination of Pex5p occurs on a
      cysteine residue.

PMID- 17550899
TI  - Werner helicase-interacting protein 1 binds polyubiquitin via its zinc finger
      domain.
AB  - DNA repair is regulated on many levels by ubiquitination. In order to identify
      novel connections between DNA repair pathways and ubiquitin signaling, we used
      mass spectrometry to identify proteins that interact with lysine 6-linked
      polyubiquitin chains. From this proteomic screen, we identified the DNA repair
      protein WRNIP1 (Werner helicase-interacting protein 1), along with nucleosome
      assembly protein 1, as novel ubiquitin-interacting proteins. We found that a
      small zinc finger domain at the N terminus of WRNIP1 is sufficient and necessary
      for noncovalent ubiquitin binding. This ubiquitin-binding zinc finger (UBZ)
      domain binds polyubiquitin but not monoubiquitin and appears to show no
      specificity for polyubiquitin chain linkage. A homologous zinc finger domain in
      RAD18 also binds polyubiquitin, suggesting a wider role for the UBZ domain in DNA
      repair. The WRNIP1 ubiquitin-binding function, along with its previously
      established ATPase activity, suggests that WRNIP1 plays a role in the metabolism
      of ubiquitinated proteins. Supporting this model, deletion of MGS1, the yeast
      homolog of WRNIP1, slows the rate of ubiquitin turnover, rendering yeast
      resistant to cycloheximide. We also find that WRNIP1 is heavily modified with
      ubiquitin and SUMO, revealing complex layers in the involvement of ubiquitin
      pathway proteins in the regulation of DNA repair. The novel ubiquitin-binding
      ability of WRNIP1 sheds light on the role of UBZ domain-containing proteins in
      postreplication DNA repair.

PMID- 17550900
TI  - Liver-specific knockdown of JNK1 up-regulates proliferator-activated receptor
      gamma coactivator 1 beta and increases plasma triglyceride despite reduced
      glucose and insulin levels in diet-induced obese mice.
AB  - The c-Jun N-terminal kinases (JNKs) have been implicated in the development of
      insulin resistance, diabetes, and obesity. Genetic disruption of JNK1, but not
      JNK2, improves insulin sensitivity in diet-induced obese (DIO) mice. We applied
      RNA interference to investigate the specific role of hepatic JNK1 in contributing
      to insulin resistance in DIO mice. Adenovirus-mediated delivery of JNK1 short
      hairpin RNA (Ad-shJNK1) resulted in almost complete knockdown of hepatic JNK1
      protein without affecting JNK1 protein in other tissues. Liver-specific knockdown
      of JNK1 resulted in significant reductions in circulating insulin and glucose
      levels, by 57 and 16%, respectively. At the molecular level, JNK1 knockdown mice
      had sustained and significant increase of hepatic Akt phosphorylation.
      Furthermore, knockdown of JNK1 enhanced insulin signaling in vitro. Unexpectedly,
      plasma triglyceride levels were robustly elevated upon hepatic JNK1 knockdown.
      Concomitantly, expression of proliferator-activated receptor gamma coactivator 1
      beta, glucokinase, and microsomal triacylglycerol transfer protein was increased.
      Further gene expression analysis demonstrated that knockdown of JNK1 up-regulates
      the hepatic expression of clusters of genes in glycolysis and several genes in
      triglyceride synthesis pathways. Our results demonstrate that liver-specific
      knockdown of JNK1 lowers circulating glucose and insulin levels but increases
      triglyceride levels in DIO mice.

PMID- 17550901
TI  - TRPV6 is a Ca2+ entry channel essential for Ca2+-induced differentiation of human
      keratinocytes.
AB  - Ca(2+) is an essential factor inducing keratinocyte differentiation due to the
      natural Ca(2+) gradient in the skin. However, the membrane mechanisms that
      mediate calcium entry and trigger keratinocyte differentiation had not previously
      been elucidated. In this study we demonstrate that Ca(2+)-induced differentiation
      up-regulates both mRNA and protein expression of a transient receptor potential
      highly Ca(2+)-selective channel, TRPV6. The latter mediates Ca(2+) uptake and
      accounts for the basal [Ca(2+)](i) in human keratinocytes. Our results show that
      TRPV6 is a prerequisite for keratinocyte entry into differentiation, because the
      silencing of TRPV6 in human primary keratinocytes led to the development of
      impaired differentiated phenotype triggered by Ca(2+). The expression of such
      differentiation markers as involucrin, transglutaminase-1, and cytokeratin-10 was
      significantly inhibited by small interfering RNA-TRPV6 as compared with
      differentiated control cells. TRPV6 silencing affected cell morphology and the
      development of intercellular contacts, as well as the ability of cells to
      stratify. 1,25-Dihydroxyvitamin D3, a cofactor of differentiation, dose
      dependently increased TRPV6 mRNA and protein expression in human keratinocytes.
      This TRPV6 up-regulation led to a significant increase in Ca(2+) uptake in both
      undifferentiated and differentiated keratinocytes. We conclude that TRPV6
      mediates, at least in part, the pro-differentiating effects of 1,25
      dihydroxyvitamin D3 by increasing Ca(2+) entry, thereby promoting
      differentiation. Taken together, these data suggest that the TRPV6 channel is a
      key element in Ca(2+)/1,25-dihydroxyvitamin D3-induced differentiation of human
      keratinocytes.

PMID- 17550902
TI  - Opioid receptor pharmacological chaperones act by binding and stabilizing newly
      synthesized receptors in the endoplasmic reticulum.
AB  - Accumulating evidence has indicated that membrane-permeable G protein-coupled
      receptor ligands can enhance cell surface targeting of their cognate wild-type
      and mutant receptors. This pharmacological chaperoning was thought to result from
      ligand-mediated stabilization of immature receptors in the endoplasmic reticulum
      (ER). In the present study, we directly tested this hypothesis using wild-type
      and mutant forms of the human delta-opioid receptor as models. ER-localized
      receptors were isolated by expressing the receptors in HEK293 cells under tightly
      controlled tetracycline induction and blocking their ER export with brefeldin A.
      The ER-retained delta-opioid receptor precursors were able to bind
      [(3)H]diprenorphine with high affinity, and treatment of cells with an opioid
      antagonist naltrexone led to a 2-fold increase in the number of binding sites.
      After removing the transport block, the antagonist-mediated increase in the
      number of receptors was detectable at the cell surface by flow cytometry and cell
      surface biotinylation assay. Importantly, opioid ligands, both antagonists and
      agonists, were found to stabilize the ER-retained receptor precursors in an in
      vitro heat inactivation assay and the treatment enhanced dissociation of receptor
      precursors from the molecular chaperone calnexin. Thus, we conclude that
      pharmacological chaperones facilitate plasma membrane targeting of delta-opioid
      receptors by binding and stabilizing receptor precursors, thereby promoting their
      release from the stringent ER quality control.

PMID- 17550903
TI  - Parameters characterizing implantable defibrillator output: a proposal.
AB  - AIMS: Recently, a discussion was carried out in Heart Rhythm on the
      specifications that could characterize implantable defibrillators. It is the
      intention of this paper to participate in this discussion on defibrillation
      characteristics and to give recommendations on how this problem could be solved.
      Theoretical considerations and results There are different defibrillation
      theories, all finding that the defibrillation's efficacy depends on the time
      constant RC which is output capacitance C times load resistance R. Efficacy
      decreases with increasing RC. This means that (i) the knowledge of C is of
      paramount importance, (ii) the energy is 'devalued' with increasing RC and that
      those parameter settings such as tilt or pulse duration should be adjusted to the
      time constant, and (iii) the energy values given without further specification
      are not meaningful. As there is always a voltage drop across an internal
      resistance within the ICD, the measured voltage across the output differs from
      the capacitor voltage and is reduced which determines the efficiency of the
      device. From the data given by Thammanomai et al., one can determine the
      parameters maximum voltage, capacitance, internal resistance, and tilt. These
      parameters are adequate and necessary to describe an ICD device and to derive the
      effective energy for device comparison. Discussion The 'high output devices' with
      their high nominal energy are reduced in their effective energies to a degree
      that they are comparable to the best 'standard output devices'. They do not offer
      that superiority which is promised by the nominal energy. Moreover, if the tilt
      is fixed and larger than optimal, the energy requirements are still higher or the
      effective energy will further drop. The term 'delivered energy' is not used by us
      because the delivered energy increases with increasing tilt. However, today's
      tilts are too large as judged by theories, which means that high delivered
      energies can be worse than lower ones. The delivered energy is, therefore, not a
      meaningful parameter in judging ICDs. CONCLUSION: ICD devices should be
      characterized by: (i) voltage, (ii) capacitance, (iii) tilt or pulse duration (if
      not programmable), and (iv) internal resistance. All other parameters can be
      derived from them by simple calculations. Introduction of a 'devaluation factor'
      characterizes the decreasing efficacy with increasing time constant and renders
      the output characteristics transparent and comparable.

PMID- 17550904
TI  - Daily, weekly, monthly, and seasonal patterns in the occurrence of vasovagal
      syncope in an older population.
AB  - AIMS: The aim of this study was to assess the frequency of vasovagal episodes
      over the day, week, month, and seasons. METHODS AND RESULTS: This study was part
      of the multi-centre International Study on Syncope of Uncertain Etiology-2 (ISSUE
      2), which included patients, aged 30 years or older, with severe neurally
      mediated syncope between June 2002 and July 2004. The Implantable Loop Recorder
      (ILR) was used to document the syncope-related ECG periods. For this study
      patients with recorded syncopal episodes after ILR-implantation was selected. At
      least one episode was documented in 106 patients. A higher number of episodes
      were documented during the morning than during other periods of the day (P <
      0.01). There was no difference between various days of the week, episodes per
      month, or between seasons. There was no difference between age and gender groups,
      although elderly patients seemed to be responsible for the peak in the morning.
      CONCLUSION: A circadian pattern in the frequency of vasovagal episodes exists,
      with a peak in the morning. This is in accordance with reports of diurnal
      variations in blood pressure and heart rate. No difference was observed in
      syncope distribution between days of the week, months, or seasons.

PMID- 17550905
TI  - Major regression of severe mitral regurgitation in an adult with congenital heart
      disease and cardiac resynchronization therapy.

PMID- 17550906
TI  - Sinus node function in children with congenital complete atrioventricular block.
AB  - AIMS: Children with congenital complete atrioventricular block (CCAVB) often need
      pacemaker therapy. In these children, it may be preferable to use single-lead VDD
      pacing, but for VDD pacing a normal sinus node function is required. Our aim was
      to study sinus node function in children with CCAVB. METHODS AND RESULTS: We
      longitudinally evaluated sinus rate in 36 children with CCAVB and normal anatomy
      of the heart. The rate of sinus rhythm on a 12-lead ECG, in Holter recordings,
      and exercise tests were evaluated at regular intervals. Age at the first visit of
      the children was 2.5+/-3.3 years (mean+/-SD). Follow-up was 10.6+/-7.3 years. The
      rate of sinus rhythm on a 12-lead ECG was at every age within the normal values
      for age (e.g. 0-1 year: 153+/-24 bpm, and 17-18 years: 76+/-4 bpm). Lowest and
      highest sinus rates in the Holter recordings were normal. During exercise, mean
      sinus rate in the total group of children increased from 92+/-8 at rest to 171+/
      9 bpm at maximal exercise. CONCLUSION: We conclude that sinus node function is
      normal in children with CCAVB. Because of the normal increase in sinus rate
      during exercise, a single-lead VDD pacemaker can be safely implanted in these
      children.

PMID- 17550907
TI  - The neurology of disgust.

PMID- 17550908
TI  - Schwann cell precursors: a favourable cell for myelin repair in the Central
      Nervous System.
AB  - Cell transplant therapies are currently under active consideration for a number
      of degenerative diseases. In the immune-mediated demyelinating-neurodegenerative
      disease multiple sclerosis (MS), only the myelin sheaths of the CNS are lost,
      while Schwann cell myelin of the PNS remains normal. This, and the finding that
      Schwann cells can myelinate CNS axons, has focussed interest on Schwann cell
      transplants to repair myelin in MS. However, the experimental use of these cells
      for myelin repair in animal models has revealed a number of problems relating to
      the incompatibility between peripheral glial cells and the CNS glial environment.
      Here, we have tested whether these difficulties can be avoided by using an
      earlier stage of the Schwann cell lineage, the Schwann cell precursor (SCP). For
      direct comparison of these two cell types, we implanted Schwann cells from post
      natal rat nerves and SCPs from embryo day 14 (E14) rat nerves into the CNS under
      various experimental conditions. Examination 1 and 2 months later showed that in
      the presence of naked CNS axons, both types of cell form myelin that
      antigenically and ultrastructurally resembles that formed by Schwann cells in
      peripheral nerves. In terms of every other parameter we studied, however, the
      cells in these two implants behaved remarkably differently. As expected from
      previous work, Schwann cell implants survive poorly unless the cells find axons
      to myelinate, the cells do not migrate significantly from the implantation site,
      fail to integrate with host oligodendrocytes and astrocytes, and form little
      myelin when challenged with astrocyte-rich environment in the retina. Following
      SCP implantation, on the other hand, the cells survive well, migrate through
      normal CNS tissue, interface smoothly and intimately with host glial cells and
      myelinate extensively among the astrocytes of the retina. Furthermore, when
      implanted at a distance from a demyelinated lesion, SCPs but not Schwann cells
      migrate through normal CNS tissue to reach the lesion and generate new myelin.
      These features of SCP implants are all likely to be helpful attributes for a
      myelin repair cell. Since these cells also form Schwann cell myelin that is
      arguably likely to be resistant to MS pathology, they share some of the main
      advantages of Schwann cells without suffering from the disadvantages that render
      Schwann cells less than ideal candidates for transplantation into MS lesions.

PMID- 17550909
TI  - Floral morphogenesis in Euptelea (Eupteleaceae, Ranunculales).
AB  - BACKGROUND AND AIMS: Based on molecular phylogenetic studies, the unigeneric
      family Eupteleaceae has a prominent phylogenetic position at or near the base of
      Ranunculales, which, in turn, appear at the base of eudicots. The aim of the
      present paper is to reveal developmental features of the flowers and to put the
      genus in a morphological context with other basal eudicots. METHODS: Flowers in
      all developmental stages of Euptelea pleiosperma were collected in the wild at
      intervals of 7-10 d in the critical stages and studied with a scanning electron
      microscope. KEY RESULTS: Remnants of a perianth are lacking throughout flower
      development. Floral symmetry changes from monosymmetric to asymmetric to
      disymmetric during development. Asymmetry is expressed in that the sequence of
      stamen initiation is from the centre to both lateral sides on the adaxial side of
      the flower but starting from one lateral side and proceeding to the other on the
      abaxial side. Despite the pronounced floral disymmetry, a dimerous pattern of
      floral organs was not found. The carpel primordia arise between the already large
      stamens and alternate with them. Stamens and carpels each form a somewhat
      irregular whorl. The carpels are ascidiate from the beginning. The stigma
      differentiates as two crests along the ventral slit of the ovary. The few lateral
      ovules alternate with each other. CONCLUSIONS: Although the flowers have some
      unusual autapomorphies (wind pollination, lack of a perianth, pronounced
      disymmetry of the floral base, long connective protrusion, long temporal gap
      between androecium and gynoecium initiation, small space for carpel initiation),
      they show some plesiomorphies at the level of basal eudicots (free carpels,
      basifixed anthers, whorled phyllotaxis), and thus fit well in Ranunculales.

PMID- 17550910
TI  - Functional utrastructure of Genlisea (Lentibulariaceae) digestive hairs.
AB  - BACKGROUND AND AIMS: Digestive structures of carnivorous plants produce external
      digestive enzymes, and play the main role in absorption. In Lentibulariaceae, the
      ultrastructure of digestive hairs has been examined in some detail in Pinguicula
      and Utricularia, but the sessile digestive hairs of Genlisea have received very
      little attention so far. The aim of this study was to fill this gap by expanding
      their morphological, anatomical and histochemical characterization. METHODS:
      Several imaging techniques were used, including light, confocal and electron
      microscopy, to reveal the structure and function of the secretory hairs of
      Genlisea traps. This report demonstrates the application of cryo-SEM for fast
      imaging of whole, physically fixed plant secretory structures. KEY RESULTS AND
      CONCLUSION: The concentration of digestive hairs along vascular bundles in
      subgenus Genlisea is a primitive feature, indicating its basal position within
      the genus. Digestive hairs of Genlisea consist of three compartments with
      different ultrastructure and function. In subgenus Tayloria the terminal hair
      cells are transfer cells, but not in species of subgenus Genlisea. A digestive
      pool of viscous fluid occurs in Genlisea traps. In spite of their similar
      architecture, the digestive-absorptive hairs of Lentibulariaceae feature
      differences in morphology and ultrastructure.

PMID- 17550911
TI  - Finding cis-regulatory modules in Drosophila using phylogenetic hidden Markov
      models.
AB  - MOTIVATION: Finding the regulatory modules for transcription factors binding is
      an important step in elucidating the complex molecular mechanisms underlying
      regulation of gene expression. There are numerous methods available for solving
      this problem, however, very few of them take advantage of the increasing
      availability of comparative genomic data. RESULTS: We develop a method for
      finding regulatory modules in Eukaryotic species using phylogenetic data. Using
      computer simulations and analysis of real data, we show that the use of
      phylogenetic hidden Markov model can lead to an increase in accuracy of
      prediction over methods that do not take advantage of the data from multiple
      species. AVAILABILITY: The new method is made accessible under GPL in a new
      publicly available JAVA program: EvoPromoter. It can be downloaded at
      http://sourceforge.net/projects/evopromoter/.

PMID- 17550912
TI  - Classification of small molecules by two- and three-dimensional decomposition
      kernels.
AB  - MOTIVATION: Several kernel-based methods have been recently introduced for the
      classification of small molecules. Most available kernels on molecules are based
      on 2D representations obtained from chemical structures, but far less work has
      focused so far on the definition of effective kernels that can also exploit 3D
      information. RESULTS: We introduce new ideas for building kernels on small
      molecules that can effectively use and combine 2D and 3D information. We tested
      these kernels in conjunction with support vector machines for binary
      classification on the 60 NCI cancer screening datasets as well as on the NCI HIV
      data set. Our results show that 3D information leveraged by these kernels can
      consistently improve prediction accuracy in all datasets. AVAILABILITY: An
      implementation of the small molecule classifier is available from
      http://www.dsi.unifi.it/neural/src/3DDK.

PMID- 17550913
TI  - Alvira: comparative genomics of viral strains.
AB  - MOTIVATION: The Alvira tool is a general purpose multiple sequence alignment
      viewer with a special emphasis on the comparative analysis of viral genomes. This
      new tool has been devised specifically to address the problem of the simultaneous
      analysis of a large number of viral strains. The multiple alignment is embedded
      in a graph that can be explored at different levels of resolution. AVAILABILITY:
      The Alvira software is available at: http://bioinfo.genopole
      toulouse.prd.fr/Alvira. SUPPLEMENTARY INFORMATION: A tutorial is available at
      Alvira's homepage.

PMID- 17550914
TI  - A global approach to identify differentially expressed genes in cDNA (two-color)
      microarray experiments.
AB  - MOTIVATION: Currently most of the methods for identifying differentially
      expressed genes fall into the category of so called single-gene-analysis,
      performing hypothesis testing on a gene-by-gene basis. In a single-gene-analysis
      approach, estimating the variability of each gene is required to determine
      whether a gene is differentially expressed or not. Poor accuracy of variability
      estimation makes it difficult to identify genes with small fold-changes unless a
      very large number of replicate experiments are performed. RESULTS: We propose a
      method that can avoid the difficult task of estimating variability for each gene,
      while reliably identifying a group of differentially expressed genes with low
      false discovery rates, even when the fold-changes are very small. In this
      article, a new characterization of differentially expressed genes is established
      based on a theorem about the distribution of ranks of genes sorted by (log)
      ratios within each array. This characterization of differentially expressed genes
      based on rank is an example of all-gene-analysis instead of single gene analysis.
      We apply the method to a cDNA microarray dataset and many low fold-changed genes
      (as low as 1.3 fold-changes) are reliably identified without carrying out
      hypothesis testing on a gene-by-gene basis. The false discovery rate is estimated
      in two different ways reflecting the variability from all the genes without the
      complications related to multiple hypothesis testing. We also provide some
      comparisons between our approach and single-gene-analysis based methods.
      SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics
      online.

PMID- 17550915
TI  - dPattern: transcription factor binding site (TFBS) discovery in human genome
      using a discriminative pattern analysis.
AB  - MOTIVATION: Transcription factor binding sites (TFBSs) are typically short in
      length, thus search with a profile model from known TFBSs produces many false
      positives. When combined with additional information, gene expression data in
      this article, sensitivity and specificity of TFBS search can be improved
      significantly. RESULTS: By modifying our previous REFINEMENT approach, we
      developed dPattern that searches for occurrences of TFBSs in the promotor regions
      of up/down regulated or random genes.

PMID- 17550916
TI  - Differential effects of strength versus power training on bone mineral density in
      postmenopausal women: a 2-year longitudinal study.
AB  - OBJECTIVES: To investigate the effect of two different schemes of loading in
      resistance training on bone mineral density (BMD) and pain in pretrained
      postmenopausal women. METHODS: 53 pretrained women (mean (SD) age 58.2 (3.7)
      years) who carried out a mixed resistance and gymnastics programme were randomly
      assigned to a strength training (ST) or power training (PT) group. The difference
      between the two groups was the movement velocity during the resistance training
      (ST, 4 s (concentric)/4 s (eccentric); PT, explosive/4 s). Otherwise both groups
      carried out periodised progressive resistance training (10-12 exercises, 2-4
      sets, 4-12 repetitions at 70-92.5% of the one-repetition maximum (2/week) for 2
      years. Mechanical loading was determined with a force measuring plate during the
      leg press exercise. At baseline and after 2 years, BMD was measured at different
      sites with dual x-ray absorptiometry. Pain was assessed by questionnaire.
      RESULTS: Loading magnitude, loading/unloading rate, loading amplitude and loading
      frequency differed significantly (p<0.001) between the two groups. After 2 years,
      significant between-group differences were detected for BMD (PT, -0.3%; ST, 
      2.4%; p<0.05) and bone area (PT, 0.4%; ST, -0.9%; p<0.05) at the lumbar spine. At
      the hip, there was a non-significant trend in favour of the PT group. Also the
      incidence of pain indicators at the lumbar spine was more favourable in the PT
      group. CONCLUSION: The results show that PT may be superior for maintaining BMD
      in postmenopausal women. Furthermore, PT was safe as it did not lead to increased
      injury or pain.

PMID- 17550917
TI  - Noise-enhanced postural stability in subjects with functional ankle instability.
AB  - OBJECTIVE: To examine the effects of stochastic resonance (SR) stimulation on the
      postural stability of subjects with functional ankle instability (FAI). DESIGN:
      Experimental research design. SETTING: Sports medicine research laboratory.
      PARTICIPANTS: 12 subjects with FAI who reported a history of recurrent ankle
      sprains and "giving way" sensations at the ankle. INTERVENTIONS: Subjects
      performed 20 s single-leg balance tests under SR stimulation at 0.05 mA and 0.01
      mA and under control conditions. Testing order was randomised. Stimulators that
      delivered subsensory stimulation to ankle muscles and ligaments were worn.
      Subjects were blinded to the test conditions, as SR stimulation was subsensory
      and stimulators were turned off during the control condition. MAIN OUTCOME
      MEASURES: Anterior/posterior and medial/lateral centre-of-pressure velocities
      (COPVs) were combined to form a resultant vector (COPV-R). The COPV-R differences
      between the optimal SR stimulation and control conditions were analysed. Optimal
      SR stimulation was defined as the SR stimulation input intensity level (0.05 mA
      or 0.01 mA) that produced the greatest percentage improvement in postural
      stability compared with the control condition. Slower velocities indicated
      enhanced postural stability. RESULTS: The optimal input intensity was 0.05 mA for
      nine subjects and 0.01 mA for the other three. The optimal SR stimulation
      significantly (p<0.05) improved COPV-R compared with the control condition (6.60
      (1.06) vs 7.20 (1.03) cm/s; mean (SD)). CONCLUSION: SR stimulation may enhance
      signal detection of sensorimotor signals associated with postural stability. This
      result has clinical relevance as improvements in postural instability associated
      with FAI may decrease ankle sprain injury.

PMID- 17550918
TI  - ACTN3 genotype in professional soccer players.
AB  - The authors studied the frequency distribution of alpha-actinin-3 (ACTN3) R577X
      genotypes in 60 top-level professional soccer players. The results were compared
      with those of 52 elite endurance athletes and 123 sedentary controls. The per
      cent distribution of RR and RX genotypes in soccer players (48.3% and 36.7%) was
      significantly higher and lower, respectively, than controls (28.5% and 53.7%) and
      endurance athletes (26.5% and 52%) (p = 0.041). Although there are notable
      exceptions, elite soccer players tend to have the sprint/power ACTN3 genotype.

PMID- 17550919
TI  - Risk of injury on artificial turf and natural grass in young female football
      players.
AB  - BACKGROUND: Artificial turf is becoming increasingly popular, although the risk
      of injury on newer generations of turf is unknown. AIM: To investigate the risk
      of injury on artificial turf compared with natural grass among young female
      football players. STUDY DESIGN: Prospective cohort study. METHODS: 2020 players
      from 109 teams (mean (SD) 15.4 (0.8) years) participated in the study during the
      2005 football season. Time-loss injuries and exposure data on different types of
      turf were recorded over an eight-month period. RESULTS: 421 (21%) players
      sustained 526 injuries, leading to an injury incidence of 3.7/1000 playing hours
      (95% CI 3.4 to 4.0). The incidence of acute injuries on artificial turf and grass
      did not differ significantly with respect to match injuries (rate ratio (RR) 1.0,
      95% CI 0.8 to 1.3; p = 0.72) or training injuries (RR 1.0, 95% CI 0.6 to 1.5, p =
      0.93). In matches, the incidence of serious injuries was significantly higher on
      artificial turf (RR 2.0, 95% CI 1.3 to 3.2; p = 0.03). Ankle sprain was the most
      common type of injury (34% of all acute injuries), and there was a trend towards
      more ankle sprains on artificial turf than on grass (RR 1.5, 95% CI 1.0 to 2.2; p
      = 0.06). CONCLUSION: In the present study among young female football players,
      the overall risk of acute injuries was similar between artificial turf and
      natural grass.

PMID- 17550920
TI  - Computer-based quantification of the mean Achilles tendon thickness in ultrasound
      images: effect of tendinosis.
AB  - BACKGROUND: B-mode measurement of the sagital diameter of the Achilles tendon
      based on a manual tracing (MT) procedure is partly dependent on the subjectivity
      of the reader. The aim of this study is to establish a standardised automatic
      procedure to differentiate between normal and chronically degenerated tendons.
      For this comparison, the tracing results of the tendon boundaries of an automatic
      identification (AI) process, already established with the detection of intima
      media thickness, are compared with computer-assisted MT. METHODS: The detection
      of the tendon boundaries was performed in 115 ultrasound images including the
      cranial border of the calcaneal tuberosity. The measured section (starting point
      4 cm away from the anterior boundary of the calcaneal tuberosity) amounted to 3
      cm, and was divided into three sub-segments (1 cm each). Intra- and inter
      reader/observer variability for mean and maximum Achilles tendon thickness (ATT)
      with AI and MT were evaluated. A normal group and a group with clinically
      diagnosed chronic tendon degeneration had mean and maximum ATT readings compared.
      RESULTS: Using MT, the intra- and inter-reader variability was 3.0% and 6.8%,
      respectively, using AI the variability was 1.6% and 3.9%, respectively. Mean and
      maximum ATT were measured systematically lower by AI compared to MT in all
      regions by 0.4 mm. The AI procedure was most accurate in the second segment. The
      mean ATT and maximum ATT were correctly detected in 93.9% and 96.6% of the
      images. CONCLUSION: The AI procedure detected the ATT with a high level of
      precision in all three segments. The most robust measurement was reached in the
      second segment. It eliminates most of the inter-/intra-reader variability in ATT
      measurement using MT. We suggest this new method could be a new gold standard for
      quantification of chronic disorder in Achilles tendons.

PMID- 17550921
TI  - Epidemiology of knee injuries among adolescents: a systematic review.
AB  - BACKGROUND: Youth sports injury is a public health concern, as it has detrimental
      effects on the health and well-being of young athletes. The knee joint is
      reported to be the most common joint injured by young sports participants. The
      potential loss of ability to participate in regular physical activity after
      injury is alarming, because physical inactivity is one of the major risk factors
      associated with systemic disease, disability and/or death worldwide. STUDY
      DESIGN: This paper presents a systematic review of the epidemiological research
      reporting on the prevalence of knee injuries among active adolescents to
      ascertain the global scope of the problem. RESULTS: The 19 eligible studies for
      this review were mostly (90%) conducted in developed countries. Global adolescent
      knee injury prevalence ranges between 10% and 25%, with more recent studies
      reporting higher percentages. The average methodological appraisal score of the
      19 studies was 56%. Females and adolescents appear to be more at an increased
      risk of sustaining a knee injury compared with males. CONCLUSIONS: Developing
      standard injury definitions as well as descriptions of injury causes must be
      taken into consideration in future injury surveillance research in order to
      appropriately inform effective knee injury preventative programmes for youth.

PMID- 17550922
TI  - Molecular architecture of the glomerular slit diaphragm: lessons learnt for a
      better understanding of disease pathogenesis.

PMID- 17550923
TI  - The cost of implementing UK guidelines for the management of chronic kidney
      disease.
AB  - BACKGROUND: Chronic kidney disease (CKD) is a major public health problem. In the
      UK, guidelines have been developed to facilitate case identification and
      management. Our aim was to estimate the annualized cost of implementation of the
      guidelines on newly identified CKD cases. METHODS: We interrogated the New
      Opportunities for Early Renal Intervention by Computerised Assessment (NEOERICA)
      database using a Java program created to recompile the CKD guidelines into rule
      based decision trees. This categorized all patients with a serum creatinine
      recorded over a 1-year period into those requiring more tests or referral. A 12
      month cost analysis for following the guidelines was performed. RESULTS: In the
      first year, a practice of 10,000 would identify 147.5 patients with stages 3-5
      CKD over and above those already known. All stages 4-5 CKD cases would require
      nephrology referral. Of those with stage 3 CKD (143.85), 126.27 stable patients
      would require more tests. The following would require referral: 14.8 with
      estimated glomerular filtration rate decline>or=5 ml/min/1.73 m2/year, 1.11 with
      haemoglobin<11 g/dl and 1.67 with blood pressure>150/90 on three anti
      hypertensives. The projected cost per practice of investigating stable stage 3
      CKD was euro 6111; and euro 7836 for nephrology referral. Total costs of euro 17
      133 in the first year were increased to euro 29,790 through the effect of
      creatinine calibration. CONCLUSIONS: CKD guideline implementation results in
      significant increases in nephrology referral and additional investigation. These
      costs could be recouped by delaying dialysis requirement by 1 year in one
      individual per 10,000 patients managed according to guidelines.

PMID- 17550924
TI  - Expression of glomerular heparan sulphate domains in murine and human lupus
      nephritis.
AB  - BACKGROUND: Recently, we identified specific N- and 6-O-sulphated heparan
      sulphate (HS) domains on activated glomerular endothelial cells. In this study,
      we evaluated in lupus nephritis the expression of different HS domains on
      glomerular endothelium and in the glomerular basement membrane (GBM). METHODS:
      The expression of specific glomerular HS domains and the presence of
      immunoglobulins (Ig) were determined by immunofluorescence staining of kidney
      sections of patients with nephritis due to systemic lupus erythematosus (SLE) and
      MRL/lpr lupus mice. The expression/presence of glomerular HS domains and Ig was
      also evaluated after eluting Ig from renal sections of lupus mice using two
      elution methods, and in renal sections of lupus mice treated with heparinoids.
      RESULTS: Both MRL/lpr mice and patients with lupus nephritis showed a decreased
      expression of HS in the GBM. The expression of N- and 6-O-sulphated HS domains on
      glomerular endothelium was decreased in MRL/lpr mice, but increased in SLE
      patients. MRL/lpr mice had more extensive glomerular Ig deposits than SLE
      patients. After elution of Ig, the glomerular endothelial expression of N- and 6
      O-sulphated HS domains in MRL/lpr mice was recovered and even increased above
      normal levels, while the expression of HS in the GBM was restored to normal
      levels. Treatment with heparinoids prevented Ig deposition and preserved the
      expression of glomerular HS domains at normal levels in lupus mice. CONCLUSION:
      The expression of specific HS domains on glomerular endothelium and in the GBM is
      changed during lupus nephritis due to masking by Ig deposits and induction of
      inflammatory N- and 6-O-sulphated HS domains.

PMID- 17550925
TI  - Renoprotective effects of sirolimus in non-immune initiated focal segmental
      glomerulosclerosis.
AB  - BACKGROUND: In this study we tested the hypothesis that sirolimus (a target of
      rapamycin inhibitor that attenuates intrinsic renal and immune cell
      proliferation) reduces glomerular hypertrophy and tubular epithelial cell (TEC)
      proliferation, and attenuates the progression of renal scarring and dysfunction,
      in a non-immune initiated model of focal segmental glomerulosclerosis (FSGS).
      METHODS: Adult male Wistar rats with adriamycin nephropathy (AN) were stratified
      into two groups, according to proteinuria on day 12, and received either vehicle
      (dimethylsulphoxide) or sirolimus (0.1 mg/kg) by daily subcutaneous injection,
      from day 14 until day 49 (n = 8 each). Control animals were also examined (n = 3
      each). RESULTS: Sirolimus did not affect the progression of proteinuria, renal
      dysfunction, hypercholesterolaemia, body weight or alter intraluminal cast
      formation in AN. Sirolimus prevented the increase in kidney enlargement in AN,
      and attenuated glomerular capillary tuft expansion, glomerulosclerosis and
      periglomerular myofibroblast accumulation. In the tubulointerstitium, sirolimus
      attenuated tubular dilatation, TEC proliferation and interstitial fibrosis. This
      was accompanied by a reduction in renal cortical TGF-beta1, but peritubular
      myofibroblast accumulation and renal inflammation (glomerular and interstitial ED
      1 and CD3-positive cell accumulation), were unaffected. CONCLUSION: The anti
      renotrophic properties of sirolimus were correlated with a reduction in renal
      scarring in AN. These data suggest that sirolimus has renoprotective effects when
      administered during the early stages of an FSGS pattern of chronic renal injury.

PMID- 17550926
TI  - Renal protective effects of pitavastatin on spontaneously hypercholesterolaemic
      Imai Rats.
AB  - BACKGROUND: Independent of their lipid-lowering effects, 3-hydroxy-3
      methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors have renal protective
      effects on various models of progressive renal diseases, therefore, additional
      therapeutic advantages have been considered. In the present study, using
      spontaneously hypercholesterolaemic Imai rats, we examined the protective effects
      of pitavastatin on renal injuries and the oxidative modification of the low
      density lipoprotein (LDL) and high-density lipoprotein (HDL), since oxidized
      lipoproteins are speculated to be involved in the mechanism of this rat strain's
      renal injuries. METHODS: Male Imai rats were treated with pitavastatin (n = 11)
      at a dose of 100 mg/kg diet or received no specific therapy as controls (n = 11)
      from 10 to 22 weeks of age. Body weight, urinary protein excretion and serum
      constituents were evaluated every 4 weeks. At the end of the study, the effects
      of pitavastatin on the susceptibility of serum LDL and HDL to oxidation, and
      renal histology were examined. RESULTS: Pitavastatin treatment did not affect
      hyperlipidaemia, but significantly reduced proteinuria and preserved creatinine
      clearance deterioration. At the end of the study, lag times for LDL and HDL
      oxidation were prolonged by the treatment of pitavastatin to 126 and 153%,
      respectively, compared with the controlled group. The glomerulosclerosis index
      (SI) for untreated controlled rats was significantly higher than that for the
      pitavastatin-treated group. An immunohistochemistry study showed significantly
      lower numbers of ED-1 positive macrophages in the glomeruli and interstitium in
      pitavastatin-treated rats compared with those controlled. CONCLUSION:
      Pitavastatin treatment prevented renal injuries in Imai rats independent of lipid
      lowering effects. Prevention of oxidative modification of LDL and HDL may play an
      important role on the beneficial effects of pitavastatin treatment.

PMID- 17550927
TI  - Review on uraemic solutes II--variability in reported concentrations: causes and
      consequences.
AB  - The aim of this manuscript is to initiate a constructive discussion about
      deviations in measured concentrations of uraemic solutes; these deviations, if
      not perceived or handled appropriately, may lead to incorrect interpretations of
      the pathophysiological role of uraemic solutes and/or to erroneous therapeutic
      decisions. To come to an objective approach towards this problem, variability
      analysis of reported concentrations may be of help. Striking outliers should
      either be discarded or considered together with other values which are more
      consistent with the majority of reported data.

PMID- 17550928
TI  - Ischaemia imaging in type 2 diabetic kidney transplant candidates--is coronary
      angiography essential?
AB  - BACKGROUND: Coronary artery disease (CAD) remains the leading cause of death in
      type 2 diabetes mellitus (DM) patients undergoing renal transplantation. There is
      a high prevalence of silent CAD in these patients. Controversy exists regarding
      the role of dobutamine stress echocardiography (DSE) in detection of CAD. Our
      purpose was to compare DSE with coronary angiography (CA) for the detection of
      CAD in type 2 diabetic patients undergoing evaluation for renal transplantation.
      METHODS: Forty (36 male, four female) type 2 diabetic patients with end-stage
      renal disease (ESRD) were subjected to DSE followed by CA as a part of their pre
      renal transplant evaluation. The ability of DSE to predict 70% stenosis in one or
      more coronary arteries as determined by CA was evaluated. Mean age of the
      patients was 49.2 +/- 5 years (range 39-60 years). RESULTS: DSE was positive in
      10 (25%) patients, while 19 patients (48%) had a more than 70% lesion in at least
      one epicardial vessel on CA (six patients had single vessel, three had double
      vessel and 10 had triple vessel disease). The sensitivity and specificity in
      identifying CAD was 47.3 and 95.2%, respectively, while positive predictive value
      and negative predictive value was 90% and 66%. Accuracy of DSE was 72.5%. All
      four patients with diffuse diabetic coronary artery disease had negative DSE.
      CONCLUSION: DSE is a poor predictor of coronary artery disease in type 2 DM
      patients being evaluated for renal transplantation. CA should be included in
      evaluation of type 2 diabetic patients who are renal transplant candidates.

PMID- 17550929
TI  - Ionic dialysance and the assessment of Kt/V: the influence of different estimates
      of V on method agreement.
AB  - BACKGROUND: Ionic dialysance was recently introduced as a means to assess Kt/V
      (K(ID)t/V). With this method, urea distribution volume (V) has to be estimated.
      The primary aim of the present study was to assess the agreement between
      equilibrated Kt/V assessed by urea kinetic modelling (eKt/V) with K(ID)t/V taking
      into account different estimates of V, and to assess the monthly variation in V.
      Secondly, the mechanisms behind the intra-treatment changes in ionic dialysance
      and inter-treatment variability of K(ID)t/V were assessed. METHODS: Sixty-six
      patients were included. eKt/V was estimated using 30 min post-treatment sampling
      in the second generation Daugirdas equation. V was assessed by the formulae of
      Watson and Chertow (V(Watson); V(Chertow)), double-pool urea kinetic modelling
      (V(UKM)) and by ionic dialysance (V(IOD)) [Diascan; Hospal(R)]. RESULTS: The use
      of V(UKM) or V(IOD) instead of V(Watson) or V(Chertow) improved the relation
      between eKt/V and K(ID)t/V (both r = 0.93; P < 0.001 vs r = 0.84 and r = 0.81; P
      < 0.001). Mean values of eKt/V (1.19 +/- 0.21), K(ID)t/V(UKM) (1.19 +/- 0.30) and
      K(ID)t/V(IOD) (1.21 +/- 0.25) were comparable. Intra-class correlation
      coefficient of V(IOD) was 0.87 with a 1-month interval and <0.75 after 2 and 3
      months. Intra-class correlation coefficient of V(DP) was 0.79 with a 1-month
      interval and <0.75 after 2 and 3 months. Inter-treatment variation in K(ID)t/V
      during six consecutive dialysis sessions was 6.1% +/- 0.6%. Changes in blood flow
      were the main determinant of variations in K(ID)t/V (P < 0.05). During treatment,
      ionic dialysance decreased by 12 +/- 13 ml/min (P < 0.001). The decline in blood
      volume was the major determinant of the intra-dialytic change in ionic dialysance
      (P < 0.05). CONCLUSION: The use of V(IOD) and V(UKM) results in better agreement
      between eKt/V and K(ID)t/V compared with anthropometric formulae. K(ID)t/V was
      comparable with eKt/V and thus lower than expected for a single-pool method.
      V(IOD) and V(UKM), should be assessed at least monthly. K(ID)t/V varies widely
      between consecutive dialysis sessions, mainly due to differences in blood flow.
      During treatment, ionic dialysance decreases, which is related to the relative
      decline in blood volume.

PMID- 17550930
TI  - The autoantibody rheumatoid factor may be an independent risk factor for
      ischaemic heart disease in men.
AB  - BACKGROUND: Subjects with rheumatoid arthritis have an increased prevalence of
      ischaemic heart disease (IHD). This is most likely in those people with the
      autoantibody rheumatoid factor (RF). RF is strongly associated with rheumatoid
      arthritis (RA) but is also present in up to 15% of all adults. OBJECTIVE: To
      determine whether RF might identify people in a general population who also share
      an increased likelihood of developing IHD. METHODS: Subjects from the
      Hertfordshire Cohort Study were investigated for the presence of RF. Subjects
      completed a questionnaire and attended a clinic where a history of IHD was
      recorded (ECG, coronary artery bypass grafting, Rose chest pain). Associations
      between the presence of RF, antinuclear antibodies (ANA), anticardiolipin
      antibodies (ACA) and IHD in 567 men and 589 women were investigated and compared
      with traditional risk factors for IHD. RESULTS: RF was associated with an
      increased likelihood of IHD in men (odds ratio (OR) = 3.1, 95% CI 1.7 to 5.4,
      p<0.001). This increased risk could not be explained by traditional risk factors
      for IHD (mutually adjusted OR for RF 2.9 (95% CI 1.6 to 5.3), p<0.001). There was
      no significant association between RF in women or between ANA or ACA with IHD in
      men or women. CONCLUSION: This work suggests that RF is an independent risk
      factor for IHD in the general population. It lends support to the importance of
      inflammation in atherosclerosis and suggests that autoimmune processes may be
      involved. In addition, it raises the intriguing possibility that RF may have a
      direct role in the pathogenesis of IHD in some subjects.

PMID- 17550931
TI  - The quality of chest compressions during cardiopulmonary resuscitation overrides
      importance of timing of defibrillation.
AB  - BACKGROUND: We address the quality of chest compressions and the impact on
      initial defibrillation or initial chest compressions after sudden death. METHODS:
      Ventricular fibrillation was induced by occlusion of the left anterior descending
      coronary artery in 24 domestic pigs with a mean (+/- SD) weight of 40 +/- 2 kg.
      Cardiac arrest was left untreated for 5 min. Animals were then randomized to
      receive chest compressions-first or defibrillation-first and were further
      randomized to "optimal" or "conventional" chest compressions. A total of four
      groups of animals were investigated using a factorial design. For optimal chest
      compressions, the anterior posterior diameter of the chest was reduced by 25%,
      representing approximately 6 cm. Only 70% of this depth, or approximately 4.2 cm,
      represented conventional chest compressions. Chest compressions were delivered
      with a mechanical chest compressor. Defibrillation was attempted with a single
      biphasic 150-J shock. Postresuscitation myocardial function was
      echocardiographically assessed. RESULTS: Coronary perfusion pressures and end
      tidal Pco(2) were significantly lower with conventional chest compressions. With
      optimal chest compressions, either as an initial intervention or after
      defibrillation, each animal was successfully resuscitated. Fewer shocks were
      required prior to the return of spontaneous circulation after initial optimal
      chest compressions. No animals were resuscitated when conventional chest
      compressions preceded the defibrillation attempt. When defibrillation was
      attempted as the initial intervention followed by conventional chest
      compressions, two of six animals were resuscitated. CONCLUSIONS: In this animal
      model of cardiac arrest, it was the quality of the chest compressions, rather
      then the priority of either initial defibrillation or initial chest compressions,
      that was the predominant determinant of successful resuscitation.

PMID- 17550932
TI  - Effect of an inducible nitric oxide synthase inhibitor on differential flow
      exhaled nitric oxide in asthmatic patients and healthy volunteers.
AB  - Nitric oxide (NO) is produced by a variety of cells within the respiratory tract,
      particularly airway epithelial cells, and its increased concentration in asthma
      is likely to derive from inducible NO synthase (iNOS) expressed in inflamed
      airways. To evaluate whether an increased bronchial flux of NO (ie, airway wall
      NO flux [Jno] in picoliters per second) produced in the large airways is due to
      an enzyme overexpression, we administered a relatively selective iNOS inhibitor,
      aminoguanidine, by nebulization in a double-blind, placebo-controlled manner in
      asthmatic and healthy subjects and also investigated whether the same
      concentration of inhibitor has any effect on NO produced in the peripheral lungs
      (ie, alveolar NO concentration [Calv] in parts per billion [ppb]) or on the
      diffusing capacity of NO (Dno) [in picoliters per second(-1) per ppb(-1)) in the
      airways. Aminoguanidine administration resulted in a significant reduction in Jno
      compared with administration of the saline solution control in eight healthy
      subjects and in eight patients with asthma but caused no significant changes in
      Calv or in Dno in either group. No rise in BP, fall in FEV(1), or adverse effects
      were observed in either group. These results indicate that iNOS from larger
      airways is the predominant source of elevated large airway-derived NO in patients
      with asthma, and that exhaled NO from peripheral lungs is not affected by a
      nebulized iNOS inhibitor and, therefore, is more likely to be derived form
      constitutive forms of NO synthase.

PMID- 17550933
TI  - Loss of control of asthma following inhaled corticosteroid withdrawal is
      associated with increased sputum interleukin-8 and neutrophils.
AB  - BACKGROUND: The role of neutrophils in exacerbations of asthma is poorly
      understood. We examined the effect of withdrawal of inhaled corticosteroids on
      sputum inflammatory indexes in a double-blind study in patients with moderate,
      stable asthma. METHODS: Following a 2-week run in period, 24 subjects were
      randomized to receive either budesonide (400 microg bid) or placebo, and the
      study was continued for another 10 weeks. RESULTS: Loss of asthma control
      developed in 8 of 12 patients over the 10-week period of steroid withdrawal,
      whereas only 1 of 10 patients with budesonide treatment had exacerbations. Those
      with an exacerbation had increased sputum interleukin (IL)-8 (p < 0.0001) and
      increased sputum neutrophil numbers (p < 0.0001) compared to those without an
      exacerbation. The significant elevation in sputum IL-8 and neutrophil counts
      initially occurred 2 weeks prior to an exacerbation. Sputum neutrophilia
      correlated positively with changes in IL-8 levels (r(2) = 0.76, p = 0.01).
      CONCLUSIONS: Rapid withdrawal of inhaled corticosteroids results in an
      exacerbation of asthma that is preceded by an increase in sputum neutrophils and
      IL-8 concentrations, in contrast to an increase in eosinophils reported in
      previous studies in which inhaled steroids are slowly tapered.

PMID- 17550934
TI  - Proteomic analysis of peripheral T-lymphocytes in patients with asthma.
AB  - BACKGROUND: Asthma is chronic airway inflammation that occurs together with
      reversible airway obstruction. T-lymphocytes play an important role in the
      pathogenesis of asthma. Proteomic technology has rapidly developed in the
      postgenomic era, and it is now widely accepted as a complementary technology to
      genetic profiling. We investigated the changes of proteins in T-lymphocytes of
      asthma patients by using standard proteome technology: two-dimensional
      polyacrylamide gel electrophoresis (2D-PAGE), matrix-assisted laser desorption
      ionization time-of-flight mass spectrometry (MALDI-TOF-MS), and a database
      search. METHODS: The proteins of CD3+ T-lymphocytes were isolated from whole
      blood of six steroid-naive asthmatic patients and of six healthy volunteers. 2D
      PAGE was performed and the silver-stained protein spots were comparatively
      analyzed between the asthma and control groups using an image analyzer. Some
      differentially expressed spots were identified by MALDI-TOF-MS and database
      search. The messenger RNA expressions of some identified proteins were examined
      by real-time polymerase chain reaction (RT-PCR). RESULTS: Thirteen protein spots
      in the T-lymphocytes of the asthmatic patients were increased and 12 spots were
      decreased compared to those of the normal subjects. Among the identified
      proteins, the increased expression of the messenger RNA of phosphodiesterase 4C
      and thioredoxin-2 and the decreased expression of the messenger RNA of
      glutathione S-transferase M3 were confirmed by RT-PCR in the asthmatic patients.
      CONCLUSIONS: Proteomic examination of the peripheral T-lymphocytes revealed some
      differentially expressed proteins in the asthmatic patients. The possibility of
      using the differentially expressed proteins as important biomarkers and
      therapeutic targets in asthma patients warrants further studies.

PMID- 17550935
TI  - Exhaled nitric oxide levels in systemic sclerosis with and without pulmonary
      involvement.
AB  - BACKGROUND: Systemic sclerosis (SSc) is a connective tissue disorder of unknown
      etiology that is often complicated by pulmonary involvement, with pulmonary
      hypertension (PH) and interstitial lung disease (ILD) being the major causes of
      death. It has been suggested that the amount of nitric oxide (NO) in exhaled air
      may predict the onset of complications. The aim of the study was to measure
      exhaled NO in SSc patients and investigate its relationship with pulmonary
      involvement with and without PH. METHODS: Fifty patients (5 men and 45 women;
      mean age, 59.1 +/- 11.7 years [+/- SD]) with a diagnosis of SSc based on the
      preliminary criteria of the American Rheumatism Association, and 40 healthy
      control subjects (5 men and 35 women; mean age, 58.3 +/- 12.2 years) underwent
      exhaled NO measurements by means of a chemiluminescence analyzer, pulmonary
      function tests, high-resolution thorax CT, and Doppler echocardiography. RESULTS:
      Exhaled NO concentrations were significantly higher in SSc patients than control
      subjects (p = 0.02), and significantly lower in the patients with ILD and/or PH
      than in those without PH (p < 0.01). There was a significant inverse correlation
      between pulmonary artery systolic pressure and exhaled NO concentration in all of
      the studied patients (r = - 0.5, p < 0.001). CONCLUSIONS: Our results indicate
      that exhaled air NO concentrations are lower in SSc patients with lung
      involvement than in those without, and that SSc patients without ILD or PH have
      higher exhaled NO values than healthy subjects.

PMID- 17550936
TI  - Spirometry utilization for COPD: how do we measure up?
AB  - BACKGROUND: COPD is a significant cause of morbidity and mortality. Guidelines
      recommend the confirmation of a COPD diagnosis with spirometry. Limited evidence
      exists, however, documenting the frequency of spirometry use in clinical
      practice. METHODS: The National Committee for Quality Assurance recruited five
      health plans to determine the proportion of patients >/= 40 years old with a new
      diagnosis of COPD who had received spirometry during the interval starting 720
      days prior to diagnosis and ending 180 days after diagnosis. Patients were
      identified via International Classification of Diseases, Ninth Revision
      diagnostic codes for encounters during the period July 1, 2002, through June 30,
      2003. For each patient, the participating plans provided patient demographic and
      claims data from administrative data systems. RESULTS: Participating health plans
      covered 1,597,749 members with a total of 5,039 eligible COPD patients
      identified. Patients in the 40 to 64 age range had the highest percentage of new
      COPD diagnoses. Women were also slightly more likely to undergo spirometry (33.5%
      vs 29.4%, p = 0.001). Approximately 32% of patients with a new diagnosis of COPD
      had undergone spirometry in the specified interval. Spirometry frequency was
      lowest in older patients, with the lowest frequency in those >/= 75 years old.
      CONCLUSIONS: Our study suggests that approximately 32% of a broad range of
      patients with a new COPD diagnosis had undergone spirometry within the previous 2
      years to 6 months following diagnosis. In addition, spirometric testing appeared
      to decrease with increasing age. As opposed to a prior report, women were not
      less likely to have undergone spirometry. This study shows that spirometry is
      infrequently used in clinical practice for diagnosis of COPD and suggests
      opportunities for practice improvement.

PMID- 17550937
TI  - Contralateral recurrence of primary spontaneous pneumothorax.
AB  - BACKGROUND: Primary spontaneous pneumothorax (PSP) is a common disease in young
      adults. With advances in its surgical treatment, ipsilateral recurrence is < 5%.
      However, contralateral recurrence remains a significant problem. The purpose of
      this retrospective study was to identify the factors associated with
      contralateral recurrence of PSP. METHODS: From January 1997 to December 1999, 231
      patients with PSP were reviewed and evaluated after an average of 92-months of
      follow-up. The clinical features and treatment of these patients were analyzed
      retrospectively. RESULTS: Thirty-three of these patients had contralateral
      recurrence (14.3%). The average time of contralateral recurrence was 22.94
      months. In the univariate analysis (after Bonferroni correction), patients with
      contralateral recurrence of PSP had lower a body mass index (BMI) [p < 0.001],
      and higher frequency of contralateral blebs/bullae on high-resolution CT (HRCT)
      of the lung (p < 0.001). Multiple logistic regression was performed on 128
      patients with contralateral blebs/bullae on HRCT of the lung, and the results
      indicate that being underweight (BMI < 18.5 kg/m(2)) is an independent risk
      factor for contralateral recurrence (odds ratio, 5.327). All patients with
      contralateral recurrence of PSP received surgical treatment. Two patients had
      unilateral recurrences of pneumothorax during follow-up (2 of 64 video-assisted
      thoracoscopic surgeries, 3%). CONCLUSIONS: Contralateral recurrence of PSP is
      significantly more common in patients with underweight and blebs/bullae in the
      contralateral lung. Single-stage bilateral surgery may be considered for these
      patients to circumvent the need for subsequent anesthetic and operative
      procedures, and additional hospitalization.

PMID- 17550938
TI  - Early Trends in PaO(2)/fraction of inspired oxygen ratio predict outcome in lung
      transplant recipients with severe primary graft dysfunction.
AB  - BACKGROUND: The development of severe primary graft dysfunction (PGD) is a risk
      factor for perioperative death following lung transplantation. Our goal is to
      improve the predictive value of the earliest Pao(2)/fraction of inspired oxygen
      (P/F) measurements that gauge PGD severity. METHODS: We identified 96 patients
      with severe PGD (P/F < 200) at ICU arrival through a retrospective review of 431
      lung transplants performed at our institution from 1992 to 2005. The P/F trend,
      represented as quartiles of the 12-h percentage change in P/F, was analyzed using
      multivariate logistic regression. Study outcomes were 90-day death and long-term
      survival. RESULTS: The median percentage change in P/F over 12 h was + 52%
      (interquartile range, +20 to 90%). We observed the highest early mortality among
      those in the lowest quartile of the P/F trend (an increase in P/F <or= 20%).
      Ninety-day death rates decreased across the quartiles (low quartile, 32%; low-mid
      quartile, 9%; high-mid quartile, 5%; high quartile, 5%; test for trend, p =
      0.007). After adjustment for the use of cardiopulmonary bypass, those in the
      lowest quartile of P/F trend had 6.8 times the odds of early death vs patients
      with a more favorable trend (odds ratio, 6.80; 95% confidence interval, 1.73 to
      0.51; p = 0.007). In the first 5 years after transplant, there were significantly
      more deaths within the low quartile group vs those with a more rapidly increasing
      P/F trend (log-rank test, p = 0.01). CONCLUSIONS: Among lung recipients with
      severe PGD at ICU arrival, an improvement in P/F <or= 20% in the first 12 h
      portends a poor outcome.

PMID- 17550939
TI  - Spirometry can be done in family physicians' offices and alters clinical
      decisions in management of asthma and COPD.
AB  - BACKGROUND: Spirometry is recommended for diagnosis and management of obstructive
      lung disease. While many patients with asthma and COPD are cared for by primary
      care practices, limited data are available on the use and results associated with
      spirometry in primary care. OBJECT: To assess the technical adequacy, accuracy of
      interpretation, and impact of office spirometry. DESIGN: A before-and-after
      quasiexperimental design. SETTING: Three hundred eighty-two patients from 12
      family medicine practices across the United States. PARTICIPANTS: Patients with
      asthma and COPD, and staff from the 12 practices. MEASUREMENTS: Technical
      adequacy of spirometry results, concordance between family physician and
      pulmonary expert interpretations of spirometry test results, and changes in
      asthma and COPD management following spirometry testing. RESULTS: Of the 368
      tests completed over the 6 months, 71% were technically adequate for
      interpretation. Family physician and pulmonary expert interpretations were
      concordant in 76% of completed tests. Spirometry was followed by changes in
      management in 48% of subjects with completed tests, including 107 medication
      changes (>85% concordant with guideline recommendations) and 102 nonpharmacologic
      changes. Concordance between family physician and expert interpretations of
      spirometry results was higher in those patients with asthma compared to those
      with COPD. DISCUSSION AND CONCLUSIONS: US family physicians can perform and
      interpret spirometry for asthma and COPD patients at rates comparable to those
      published in the literature for international primary care studies, and the
      spirometry results modify care.

PMID- 17550940
TI  - Expression of two different sulfated fucans by females of Lytechinus variegatus
      may regulate the seasonal variation in the fertilization of the sea urchin.
AB  - The egg jellies of sea urchins contain sulfated polysaccharides with unusual
      structures, composed of linear chains of l-fucose or l-galactose with well
      defined repetitive units. The specific pattern of sulfation and the position of
      the glycosidic bond vary among sulfated polysaccharides from different species.
      These polysaccharides show species specificity in inducing the acrosome reaction,
      which is a critical event for fertilization. Females of the sea urchin Lytechinus
      variegatus spawn eggs containing a sulfated fucan with the repetitive sequence [3
      alpha-L-Fucp-2(OSO(3))-1 --> 3-alpha-L-Fucp-4(OSO(3))-1 --> 3-alpha-L-Fucp
      2,4(OSO(3))-1 --> 3-alpha-L-Fucp-2(OSO(3))-1](n). We now observe that, close to
      winter, a period of decreased fertility for the sea urchin, the females
      synthesize a distinct sulfated fucan with a simple structure, composed of 4
      sulfated, 3-linked alpha-fucose residues. This sulfated fucan is inactive when
      tested in vitro for the acrosome reaction using homologous sperm. The amount of
      egg jellies spawned by females (and their constituent sulfated polysaccharides)
      varied greatly throughout the year. Apparently, there is a correlation between
      the temperature of the sea water and the expression of the 4-sulfated, 3-linked
      sulfated fucan. Overall, we described the occurrence of two isotypes of sulfated
      fucan in the egg jelly of the sea urchin L. variegatus, which differ in their
      biological activity and may be involved in the periodicity of the reproductive
      cycle of the invertebrate.

PMID- 17550941
TI  - Intersectin enhances huntingtin aggregation and neurodegeneration through
      activation of c-Jun-NH2-terminal kinase.
AB  - Huntingon's disease is a progressive neurodegenerative disease arising from
      expansion of a polyglutamine (polyQ) tract in the protein huntingtin (Htt)
      resulting in aggregation of mutant Htt into nuclear and/or cytosolic inclusions
      in neurons. Mutant Htt affects multiple processes including protein degradation,
      transcription, signal transduction, fast axonal transport and endocytosis
      [reviewed in Ross, C.A. and Poirier, M.A. (2005) Opinion: what is the role of
      protein aggregation in neurodegeneration? Nat. Rev. Mol. Cell. Biol., 6, 891
      898]. Here, we report that the endocytic and signal transduction scaffold
      intersectin (ITSN) increased aggregate formation by mutant Htt through activation
      of the c-Jun-NH(2)-terminal kinase (JNK)-MAPK pathway. Conversely, silencing ITSN
      or inhibiting JNK attenuated aggregate formation. Using a Drosophila model for
      polyQ repeat disease, we observed that ITSN enhanced polyQ-mediated
      neurotoxicity. A reciprocal relationship was observed between ITSN and Htt. While
      ITSN enhanced Htt aggregation and toxicity, Htt, in turn, inhibited the
      cooperativity between ITSN and the epidermal growth factor receptor signal
      transduction pathway. Finally, we observed that ITSN overexpression enhanced
      aggregation of polyQ-expanded androgen receptor (AR) as well as wild-type
      versions of both Htt and AR suggesting a broader involvement of ITSN in
      neurodegenerative diseases through destabilization of polyQ-containing proteins.

PMID- 17550942
TI  - Parental age and risk of acute lymphocytic leukaemia and embryonal tumours in the
      Piedmont Region, Italy.

PMID- 17550944
TI  - Maternal smoking habits and cognitive development of children at age 4 years in a
      population-based birth cohort.
AB  - BACKGROUND: Active maternal smoking during pregnancy has been associated with a
      higher risk of behavioural disorders in children, but a few cohort studies
      measuring smoking data prospectively have studied its specific effects on the
      cognitive abilities of pre-schoolers. METHOD: A birth cohort was set up in
      Menorca Island in 1997 within the Asthma Multicenter Infants Cohort Study. A
      total of 420 (87% of those eligible) children had complete data for final
      analyses at age 4 years. Interviewer-administered questionnaires were completed
      by mothers during the third trimester of pregnancy and then every year up to age
      4 years of their child. A standardized version of the McCarthy Scales of
      Children's Abilities (MCSA) was used to evaluate the child's motor and cognitive
      capabilities. Multivariable regressions were used with MCSA's assessed outcomes
      adjusting for: home location, maternal alcohol consumption, mother's social class
      and level of education during pregnancy, parity, marital status, father's
      education level, child's gender, birth weight and height, breastfeeding duration,
      passive smoking, school season, age during test administration and evaluator
      (psychologist). RESULTS: A high global consistency in maternal smoking habits was
      found (total agreement = 88.7%). Maternal social class and education level were
      inversely associated with maternal smoking behaviour. Maternal smoking during
      pregnancy (in cig./day) was associated with a decrease (in points) of children's
      global cognitive score [beta = -0.60, (95% CI: -1.10; -0.09)]; as well as global
      cognitive sub-areas like verbal score [beta = -0.59, (95% CI: -1.11; -0.07)];
      quantitative score [beta = -0.57, (95% CI: -1.08; -0.06)]; executive function
      score [beta = -0.71, (95% CI: -1.23; -0.20)]; and working memory score [beta = 
      0.46, (95% CI: -0.92; -0.01)]. CONCLUSION: Our findings suggest an association
      with maternal smoking during pregnancy and lowered cognitive development in
      children at age 4 years.

PMID- 17550946
TI  - Commentary: Preston and mortality trends since the mid-1970s.

PMID- 17550947
TI  - Commentary: Did Preston underestimate the effect of economic development on
      mortality?

PMID- 17550948
TI  - Commentary: The Preston Curve 30 years on: still sparking fires.

PMID- 17550949
TI  - Commentary: Missed opportunities.

PMID- 17550950
TI  - Commentary: The changing relation between mortality and income.

PMID- 17550951
TI  - Commentary: Samuel Preston's 'The changing relation between mortality and level
      of economic development'.

PMID- 17550952
TI  - The changing relation between mortality and level of economic development.
      Population Studies, Vol. 29, No. 2, July 1975.

PMID- 17550953
TI  - Pediatric migraine: pharmacologic agents for prophylaxis.
AB  - OBJECTIVE: To identify and evaluate the data regarding medication use for
      migraine prophylaxis in the pediatric population. DATA SOURCES: Literature was
      obtained through searches in PubMed (Mid 1950s-March 2007), Iowa Drug Information
      Service/Web (1966-February 2007), International Pharmaceutical Abstracts (1970
      February 2007), and the Cochrane Library. The terms migraine, prophylaxis, child,
      and children were used and cross referenced with all drug names. Reference
      citations from publications identified were also reviewed and included. STUDY
      SELECTION AND DATA EXTRACTION: Only trials that evaluated migraine headaches in
      the pediatric population were included. Trials including adolescent and adult
      populations are briefly listed, but not reviewed. Trials involving non
      prescription medication were also included in the evaluation. Due to the limited
      information, all clinical trials, retrospective reviews, and abstracts evaluated
      were included in this review. DATA SYNTHESIS: Few controlled clinical trials
      regarding prophylaxis therapy are available. Currently, no medications are
      approved by the Food and Drug Administration for prophylaxis of migraines in
      children. Seventeen drugs were identified and included in the review. Of the
      drugs with available data, topiramate, valproic acid, flunarizine, amitriptyline,
      and cyproheptadine have shown efficacy in decreasing migraine frequency and
      duration in children. However, larger clinical trials are necessary to validate
      the utility of these agents. Conflicting data exist for propranolol and
      pizotifen, and additional data are needed for gabapentin, levetiracetam,
      zonisamide, naproxen, and trazodone. In clinical trials, nimodipine, clonidine,
      and natural supplements have shown a lack of efficacy versus placebo for
      prophylaxis of migraines in children. CONCLUSIONS: Topiramate, valproic acid, and
      amitriptyline have the most data on their use for prophylaxis of migraines in
      children. Numerous agents have limited data in this population and several agents
      lack efficacy. Prospective, well designed, controlled clinical trials that
      include quality-of-life and functional outcomes are needed for guiding therapy of
      migraine prophylaxis for children.

PMID- 17550954
TI  - Management of anthracycline extravasation injuries.
AB  - OBJECTIVE: To review the evidence for the management of anthracycline
      extravasation and determine the optimal treatment of such injuries. DATA SOURCES:
      A search of MEDLINE (1966-February 2007) and International Pharmaceutical
      Abstracts (1970-February 2007) was performed using the search terms
      anthracyclines and extravasation. DATA SYNTHESIS: Extravasation of anthracyclines
      can have devastating effects. After infiltration of these drugs into the
      interstitial tissue, damage may range from mild erythema and pain to severe
      tissue necrosis. Many agents have been studied in the management of these
      injuries; however, few have demonstrated efficacy and treatment remains
      controversial. Nonpharmacologic modalities shown to limit extravasation injuries
      include local tissue cooling and elevation of the affected area. Corticosteroids,
      sodium bicarbonate, hyaluronidase, hyperbaric oxygen, heparin fractions, alpha
      tocopherol, N-acetylcysteine, and granulocyte macrophage-colony stimulating
      factor have all either been shown to be ineffective or have limited data
      supporting their use. Topical dimethyl sulfoxide (DMSO) has been shown in
      prospective studies to limit the course of extravasation injuries. Dexrazoxane
      has been shown in animal models and case reports to be useful in the management
      of anthracycline extravasation. Two recent prospective clinical trials examining
      intravenous dexrazoxane 1000 mg/m2 within 6 hours of extravasation, 1000 mg/m2 24
      hours after extravasation, and 500 mg/m2 48 hours after extravasation injuries
      add to the data supporting the use of this agent in such injuries. Of the 54
      patients enrolled, surgery-requiring necrosis was avoided in 98.2%. CONCLUSIONS:
      The optimal treatment of anthracycline extravasation includes local tissue
      cooling, elevation of the afflicted extremity, dexrazoxane administration, and
      possibly topical DMSO. Many other drugs have been investigated; however, due to a
      lack of data, they cannot be recommended for the management of anthracycline
      extravasation.

PMID- 17550955
TI  - Blood glucose control by a model predictive control algorithm with variable
      sampling rate versus a routine glucose management protocol in cardiac surgery
      patients: a randomized controlled trial.
AB  - CONTEXT: Elevated blood glucose levels occur frequently in the critically ill.
      Tight glucose control by intensive insulin treatment markedly improves clinical
      outcome. OBJECTIVE AND DESIGN: This is a randomized controlled trial comparing
      blood glucose control by a laptop-based model predictive control algorithm with a
      variable sampling rate [enhanced model predictive control (eMPC); version
      1.04.03] against a routine glucose management protocol (RMP) during the peri- and
      postoperative periods. SETTING: The study was performed at the Department of
      Cardiac Surgery, University Hospital. PATIENTS: A total of 60 elective cardiac
      surgery patients were included in the study. INTERVENTIONS: Elective cardiac
      surgery and treatment with continuous insulin infusion (eMPC) or continuous
      insulin infusion combined with iv insulin boluses (RMP) to maintain euglycemia
      (target range 4.4-6.1 mmol/liter) were performed. There were 30 patients
      randomized for eMPC and 30 for RMP treatment. Blood glucose was measured in 1- to
      4-h intervals as requested by each algorithm during surgery and postoperatively
      over 24 h. MAIN OUTCOME MEASURES: Mean blood glucose, percentage of time in
      target range, and hypoglycemia events were used. RESULTS: Mean blood glucose was
      6.2 +/- 1.1 mmol/liter in the eMPC vs. 7.2 +/- 1.1 mmol/liter in the RMP group (P
      < 0.05); percentage of time in the target range was 60.4 +/- 22.8% for the eMPC
      vs. 27.5 +/- 16.2% for the RMP group (P < 0.05). No severe hypoglycemia (blood
      glucose < 2.9 mmol/liter) occurred during the study. Mean insulin infusion rate
      was 4.7 +/- 3.3 IU/h in the eMPC vs. 2.6 +/- 1.7 IU/h in the RMP group (P <
      0.05). Mean sampling interval was 1.5 +/- 0.3 h in the eMPC vs. 2.1 +/- 0.2 h in
      the RMP group (P < 0.05). CONCLUSIONS: Compared with RMP, the eMPC algorithm was
      more effective and comparably safe in maintaining euglycemia in cardiac surgery
      patients.

PMID- 17550956
TI  - Linkage of genes to total lean body mass in normal women.
AB  - BACKGROUND: Total lean body mass (LEAN-tot) is one of the three major components
      of body weight. Its deterioration is a risk factor for frailty. Despite this,
      there are few studies examining the contribution of genetic factors. OBJECTIVE:
      Our objective was to examine the contribution of genetic factors for LEAN-tot
      variation, including a genome-wide search for the genes. RESEARCH METHODS: Dual
      energy x-ray absorptiometry measurements of LEAN-tot were obtained from each of
      the 3180 United Kingdom females (509 monozygotic and 1081 dizygotic twin pairs).
      Contribution of genetic factors was assessed using variance component analysis. A
      genome-wide linkage analysis was performed on the dizygotic twins using a
      modified version of the Haseman-Elston method. RESULTS: Age, body height, total
      fat, and bone mass were correlated with LEAN-tot, and commonly explained 52% of
      the LEAN-tot variation. The crude heritability estimate was 74.0 +/- 4.0%, after
      adjustment for the aforementioned factors; 65.2 +/- 4.6% was attributable to
      independent genetic effects. Significant (P < 0.001) genetic correlations were
      found between LEAN-tot and bone mass, and LEAN-tot and total fat. Adjusted only
      for age, LEAN-tot showed no significant linkage. After adjustment for all
      covariates, significant linkage (LOD = 4.49 and 3.62) was observed at chromosome
      12q24.3 and 14q22.3, respectively. Additional peaks of interest were on 7p15.3
      15.1 (LOD = 2.86) and 8p22 (LOD = 2.83). CONCLUSIONS: LEAN-tot measured by dual
      energy x-ray absorptiometry is highly heritable, independent of other body
      measures. This first genomic search for genes associated with the lean component
      of body mass suggests significant linkage to quantitative trait loci on
      chromosomes 12 and 14.

PMID- 17550957
TI  - Association between a C/T polymorphism in exon 33 of the thyroglobulin gene is
      associated with relapse of Graves' hyperthyroidism after antithyroid withdrawal
      in Taiwanese.
AB  - CONTEXT: Graves' disease (GD) is an autoimmune disorder with genetic
      predisposition. The thyroglobulin (Tg) is a major autoantigen for GD. The human
      Tg gene polymorphism has specific features that make it important in GD.
      OBJECTIVE: This study investigated whether Tg single nucleotide polymorphisms
      (SNPs) relate to GD development in a Taiwanese population. DESIGN AND SETTING:
      This was a case-control association study. PATIENTS AND MAIN OUTCOME MEASURES: We
      enrolled 215 Taiwanese patients with GD and 141 controls from the Endocrine
      Clinic of Kaohsiung Medical University Chung-Ho Memorial Hospital. This study
      investigated the association between gene polymorphism and relapse of
      hyperthyroidism after medication was discontinued in three GD patient groups and
      a control group. We also compared clinical and laboratory data obtained from
      patients with the three different genotypes with the three different Tg SNPs
      (E10SNP158, E12SNP, and E33SNP). RESULTS: We found a significant increase in the
      T/T genotype of E33SNP compared with the control group (P < 0.001). We also found
      the E33SNP C/C genotype of the Tg gene was strongly associated with a subgroup of
      GD patients who were also characterized as having a higher relapse rate,
      significantly higher levels of persisting TSH-receptor antibody at the end of
      treatment, a higher frequency in smoking, and a higher incidence of
      ophthalmopathy (P < 0.05). CONCLUSIONS: This study showed that Taiwanese patients
      with the C/C genotype of E33SNP, smoking, ophthalmopathy, and positive TSH
      receptor antibodies at the end of the treatment were more likely to have a
      relapse of Graves' hyperthyroidism after antithyroid medication is withdrawn.

PMID- 17550958
TI  - Ghrelin suppresses secretion of luteinizing hormone in humans.
AB  - CONTEXT: Ghrelin affects the hypothalamic-pituitary-gonadal axis in various
      nonhuman mammalians, predominantly by suppressing secretion of LH. However, for
      humans, no such evidence exists. OBJECTIVE: Our objective was to study the effect
      of ghrelin on secretion of LH and testosterone in humans. DESIGN, PARTICIPANTS,
      AND INTERVENTION: Nocturnal (2000-0700 h) secretion profiles of LH and
      testosterone were determined in 10 healthy males (25.7 +/- 3.0 yr) twice,
      receiving 50 microg ghrelin or placebo at 2200, 2300, 2400, and 0100 h, in this
      single-blind, randomized, cross-over study. RESULTS: Ghrelin was associated with
      significantly (P < 0.05) lower mean plasma levels of both LH (2340-0200 h) and
      testosterone (0040-0300 h) than placebo. LH peak levels of the pulse after first
      administration of ghrelin/placebo were significantly (P = 0.014) smaller in the
      ghrelin (2.98 +/- 1.34 mIU/ml) than in the placebo condition (4.37 +/- 1.09
      mIU/ml). In addition, the interval between this and the preceding peak was
      significantly (P = 0.010) longer in the ghrelin (255.8 +/- 79.1 min) than in the
      placebo condition (190.8 +/- 51.0 min). Significantly (P = 0.005) more LH pulses
      occurred with placebo (3.2 +/- 0.75) than ghrelin (2.6 +/- 0.7) subsequent to
      ghrelin/placebo administration. CONCLUSIONS: Ghrelin caused both a delay and
      suppression of the amplitude of LH pulses. These findings are in accordance with
      those in nonhuman mammalians.

PMID- 17550959
TI  - Association of serum retinol-binding protein 4 and visceral adiposity in Chinese
      subjects with and without type 2 diabetes.
AB  - OBJECTIVE: Previous studies have shown that adipose-derived serum retinol-binding
      protein 4 (RBP4) levels are increased in insulin-resistant mouse models and in
      subjects with insulin resistance or type 2 diabetes. However, the association of
      visceral fat and serum RBP4 has not been studied. The purpose of this study was
      to investigate the relationship between serum RBP4 and regional fat distribution
      in Chinese subjects with and without type 2 diabetes. DESIGN: We measured serum
      RBP4 concentrations from 1033 Chinese subjects with various degrees of obesity
      and tested the association between visceral adiposity and serum RBP4. In a
      subgroup of this study, euglycemic-hyperinsulinemic clamp was performed to
      measure insulin sensitivity. The association between visceral adiposity and serum
      RBP4 was also determined in response to rosiglitazone treatment in a subgroup of
      patients with diabetes. RESULTS: Serum RBP4 level was positively correlated with
      visceral adipose area in male (r = 0.171; P < 0.001) and female (r = 0.215; P <
      0.001) subjects. However, there was no correlation between serum RBP4 and body
      mass index. Subjects with visceral obesity had higher serum RBP4 concentrations
      than those without visceral obesity in both men and women. Rosiglitazone
      treatment in patients with diabetes resulted in a lower serum RBP4 level (35.2 +/
      10.2 vs. 24.9 +/- 5.6 microg/ml, before vs. after treatment). These changes were
      accompanied by improved insulin sensitivity and reductions in visceral fat area.
      The latter was found to be highly correlated with the decline of serum RBP4
      levels (r = 0.471; P = 0.027). CONCLUSIONS: Serum RBP4 level is positively
      associated with visceral adiposity in both men and women. Our data suggest that
      RBP4 may contribute to the development of insulin resistance along with other
      adipokines.

PMID- 17550960
TI  - Endocrine features of menstrual cycles in middle and late reproductive age and
      the menopausal transition classified according to the Staging of Reproductive
      Aging Workshop (STRAW) staging system.
AB  - CONTEXT: Female reproductive aging based on changes in menstrual cycle length and
      frequency progresses through a number of stages as defined by the Stages of
      Reproductive Aging Workshop (STRAW) staging criteria. OBJECTIVE: This paper
      provides a comprehensive description of the endocrine features associated with
      the STRAW stages. DESIGN: Healthy women aged 21-35 and 45-55 yr submitted three
      blood samples a week over a single menstrual cycle. They were classified as mid
      reproductive age (n = 21), late-reproductive age (n = 16), early menopause
      transition (n = 16), and late menopause transition (n = 23). RESULTS: There were
      nine, one, zero, and two anovulatory cycles identified in the late menopause
      transition, early menopause transition, late-reproductive age, and mid
      reproductive age groups, respectively. Ovulatory cycle FSH, LH, and estradiol
      levels increased with progression of STRAW stage (P = 0.001, P < 0.01, and P <
      0.05, respectively), and mean luteal phase serum progesterone decreased (P <
      0.01). Early cycle (ovulatory and anovulatory) inhibin B decreased steadily
      across the STRAW stages (P < 0.01) and was largely undetectable during elongated
      ovulatory and anovulatory cycles in the menopause transition. Anti-Mullerian
      hormone decreased markedly (10- to 15-fold) and progressively across the STRAW
      stages (P < 0.01 and P < 0.001, respectively). CONCLUSIONS: Progression through
      the STRAW stages is associated with elevations in serum FSH, LH, and estradiol
      and decreases in luteal phase progesterone. The marked fall in inhibin B and
      particularly anti-Mullerian hormone indicate that they may be useful in
      predicting STRAW stage but future analyses of early cycle measurements on larger
      cohorts are needed to draw predictive conclusions.

PMID- 17550961
TI  - Combination chemotherapy including combretastatin A4 phosphate and paclitaxel is
      effective against anaplastic thyroid cancer in a nude mouse xenograft model.
AB  - CONTEXT: Anaplastic thyroid cancer (ATC) is extremely aggressive, and no
      effective treatment is available. Combretastatin A4 phosphate (CA4P), a vascular
      disrupting agent, has limited activity against ATC in a clinical trial, and so
      does paclitaxel. OBJECTIVE: We hypothesized that a triple-drug combination
      including CA4P and paclitaxel would improve efficacy against ATC. Therefore, we
      evaluated two such combinations in vivo. SETTING: We used a nude mouse xenograft
      model with ARO and KAT-4 cells. INTERVENTIONS: The first combination consisted of
      CA4P, paclitaxel, and manumycin A (a farnesyltransferase inhibitor), and the
      second, CA4P, paclitaxel, and carboplatin. MAIN OUTCOME MEASURES: Main outcome
      measures included tumor growth curves and tumor weights. RESULTS: Tumor growth
      curve analysis (linear mixed models, P < 0.05) and xenograft weight analysis
      (Kruskal-Wallis one-way ANOVA on ranks, post hoc pairwise comparison, Dunn's
      test, P < 0.05) demonstrated that both triple-drug combinations were
      significantly better than placebo for both cell lines. Anti-bromodeoxyuridine
      immunostaining of xenograft sections from animals injected with bromodeoxyuridine
      before being killed showed that CA4P alone did not inhibit DNA synthesis, but
      manumycin A and paclitaxel did. CA4P decreased the depth of the viable outer rim
      of tumor cells on xenograft sections. Using electron microscopy, we found
      blebbing/budding of endothelial cells into capillary lumens and autophagy of
      tumor cells in CA4P-treated xenografts. CONCLUSIONS: Both triple-drug
      combinations demonstrated excellent antineoplastic activity against ATC. The
      correlative findings in xenografts were consistent with vascular disruption but
      not direct inhibition of cell proliferation as the primary antineoplastic
      mechanism contributed by CA4P. These regimens warrant further investigation in
      clinical trials for ATC.

PMID- 17550962
TI  - Radioimmunoassay and tandem mass spectrometry measurement of bedtime salivary
      cortisol levels: a comparison of assays to establish hypercortisolism.
AB  - CONTEXT: Although bedtime salivary cortisol measurement has been proposed as the
      optimal screening test for the diagnosis of Cushing's syndrome, its performance
      using commercially available assays has not been widely evaluated. OBJECTIVE: Our
      objective was to compare RIA and tandem mass spectrometry (LC-MS/MS) measurement
      of salivary cortisol in obese subjects and healthy volunteers. DESIGN AND
      SETTING: We conducted a cross-sectional prospective study of outpatients.
      SUBJECTS AND METHODS: We studied 261 obese subjects (186 female) with at least
      two additional features of Cushing's syndrome and 60 healthy volunteers (30
      female). Subjects provided split bedtime salivary samples for cortisol
      measurement by commercially available RIA and LC-MS/MS. Results were considered
      normal or abnormal based on the laboratory reference range. Subjects with
      abnormal results underwent evaluation for Cushing's syndrome. RESULTS: In paired
      samples, RIA gave a lower specificity than LC-MS/MS in obese subjects (86 vs.
      94%, P = 0.008) but not healthy volunteers (86 vs. 82%, P = 0.71). Among subjects
      with at least one abnormal result, both values were abnormal in 44% (confidence
      interval 26-62%) of obese and 75% (confidence interval 33-96%) of healthy
      volunteers. In obese subjects, salivary cortisol concentrations were less than
      4.0 to 643 ng/dl (<0.11-17.7 nmol/liter; normal, < or =100 ng/dl, 2.80
      nmol/liter) by LC-MS/MS and less than 50 to 2800 ng/dl (1.4-77.3 nmol/liter;
      normal, < or =170 ng/dl, 4.7 nmol/liter) by RIA. Cushing's syndrome was not
      diagnosed in any subject. CONCLUSION: Salivary cortisol levels should not be used
      as the sole test to diagnose Cushing's syndrome if laboratory-provided reference
      ranges are used for diagnostic interpretation.

PMID- 17550963
TI  - The circadian rhythm of osteoprotegerin and its association with parathyroid
      hormone secretion.
AB  - BACKGROUND: Osteoclast resorptive activity, which is known to demonstrate
      circadian rhythmicity, is regulated by various endocrine hormones and cytokines.
      PTH suppresses osteoprotegerin (OPG), a regulator of osteoclast activity that has
      recently been shown to have a circadian rhythm in healthy controls. We studied
      the differences in the relationship between PTH, OPG, and type I collagen C
      telopeptide (betaCTX) over a 24-h period in premenopausal women, elderly
      postmenopausal women, and elderly men. METHODS: Hourly peripheral venous blood
      samples were obtained from 18 healthy non-osteoporotic volunteers: premenopausal
      women (n = 6; mean age, 30.2 +/- 2.2 yr), postmenopausal women (n = 6; mean age,
      68.2 +/- 2.6 yr), and elderly men (n = 6; mean age, 68.2 +/- 2.3 yr). Plasma PTH
      (1-84), OPG, betaCTX, and calcium were measured on all samples. Cosinor analysis
      was performed to analyze the circadian rhythm parameters. Cross-correlation
      analysis was used to determine the relationship between the time series of the
      variables. RESULTS: The 24-h mean PTH, OPG, and betaCTX concentrations were
      significantly higher in postmenopausal women as compared with premenopausal women
      and elderly men (P < 0.001). Significant circadian rhythms were observed for PTH
      (P < 0.05), OPG (P < 0.05), and betaCTX (P < 0.001) in all subjects. PTH
      secretion was characterized by two peaks in premenopausal women and elderly men
      and by a sustained increase in PTH concentration in postmenopausal women. OPG
      secretion was circadian with a daytime increase and nocturnal decrease, and a
      greater percent decrease in OPG secretion was observed in the postmenopausal
      women between 1600 and 2400 h. OPG secretion was inversely related to PTH (r = 
      0.4) and betaCTX (r = -0.6) secretion over a 24-h period. CONCLUSION: This report
      confirms a circadian rhythm for circulating OPG. The nocturnal decline in
      circulating OPG is greater in postmenopausal women as compared with premenopausal
      women and elderly men. Altered PTH secretion may contribute to the OPG secretory
      pattern in postmenopausal women resulting in increased nocturnal bone resorption.

PMID- 17550964
TI  - Role of a Galphai2 protein splice variant in the formation of an intracellular
      dopamine D2 receptor pool.
AB  - Treatment of D2-receptor-expressing cells with specific drugs upregulates the
      receptor number at the cell surface independently of protein synthesis, leading
      to the concept of an intracellular receptor pool. However, how this pool is
      operating is still an enigma. Here, we report that a splice variant of the
      Galphai2 protein, protein sGalphai2, plays a crucial role in the maintenance of
      this D2-receptor pool. Co-expression of sGi2 with D2 receptor reduced receptor
      localization to cell surface by one-third. This effect is associated with
      specific intracellular protein-protein interaction and the formation of a sGi2-D2
      receptor complex. It has been suggested that the formation of this complex serves
      to prevent D2 receptors from reaching the cell membrane. Treatment of D2-receptor
      expressing cells with agonists increased the number of cell surface D2 receptors
      and coincided with a reduction in these receptors from intracellular complexes,
      suggesting that agonist treatment released D2 receptors from the complex allowing
      them to localize to the cell membrane. Thus, in addition to elucidating how the
      intracellular pool of D2 receptor functions, our findings uncover a novel
      mechanism regulating the density of cell surface D2 receptors.

PMID- 17550965
TI  - Caveolin-1 is required for lateral line neuromast and notochord development.
AB  - Caveolae have been linked to diverse cellular functions and to many disease
      states. In this study we have used zebrafish to examine the role of caveolin-1
      and caveolae during early embryonic development. During development, expression
      is apparent in a number of tissues including Kupffer's vesicle, tailbud,
      intersomite boundaries, heart, branchial arches, pronephric ducts and periderm.
      Particularly strong expression is observed in the sensory organs of the lateral
      line, the neuromasts and in the notochord where it overlaps with expression of
      caveolin-3. Morpholino-mediated downregulation of Cav1alpha caused a dramatic
      inhibition of neuromast formation. Detailed ultrastructural analysis, including
      electron tomography of the notochord, revealed that the central regions of the
      notochord has the highest density of caveolae of any embryonic tissue comparable
      to the highest density observed in any vertebrate tissue. In addition, Cav1alpha
      downregulation caused disruption of the notochord, an effect that was enhanced
      further by Cav3 knockdown. These results indicate an essential role for caveolin
      and caveolae in this vital structural and signalling component of the embryo.

PMID- 17550966
TI  - Smad4 is required for maintaining normal murine postnatal bone homeostasis.
AB  - Transforming growth factor beta (TGFbeta) is a multifunctional cytokine involved
      in skeletal development. Smad4 is the central intracellular mediator of TGFbeta
      signaling. Our previous studies reveal that Smad4 is required for maintaining the
      normal development of chondrocytes in the growth plate. However, its biological
      function during postnatal bone remodeling is largely unknown. To investigate the
      role of Smad4 in maintaining bone homeostasis, we disrupted the Smad4 gene in
      differentiated osteoblasts using the Cre-loxP system. The Smad4 mutant mice
      exhibited lower bone mass up to 6 months of age. The proliferation and function
      of the mutant osteoblasts were significantly decreased. Bone mineral density,
      bone volume, bone formation rate and osteoblast numbers were remarkably reduced
      in Smad4 mutants. Intriguingly, the trabecular bone volume in Smad4 mutant mice
      older than 7 months was higher than that of controls whereas the calvarial and
      cortical bone remained thinner than in controls. This correlated with reduced
      bone resorption possibly caused by downregulation of TGFbeta1 and alteration of
      the ligand receptor activator of NF-kappaB (RANKL)-osteoprotegerin (OPG) axis.
      These studies demonstrate essential roles of Smad4-mediated TGFbeta signaling in
      coupling bone formation and bone resorption and maintaining normal postnatal bone
      homeostasis.

PMID- 17550967
TI  - Role of the small GTPase RhoA in the hypoxia-induced decrease of plasma membrane
      Na,K-ATPase in A549 cells.
AB  - Hypoxia impairs alveolar fluid reabsorption by promoting Na,K-ATPase endocytosis,
      from the plasma membrane of alveolar epithelial cells. The present study was
      designed to determine whether hypoxia induces Na,K-ATPase endocytosis via
      reactive oxygen species (ROS)-mediated RhoA activation. In A549 cells, RhoA
      activation occurred within 15 minutes of cells exposure to hypoxia. This
      activation was inhibited in cells infected with adenovirus coding for gluthatione
      peroxidase (an H2O2 scavenger), in mitochondria depleted (rho0) cells or cells
      expressing decreased levels of the Rieske iron-sulfur protein (inhibitor of
      mitochondrial complex III), which suggests a role for mitochondrial ROS.
      Moreover, exogenous H2O2 treatment during normoxia mimicked the effects of
      hypoxia on RhoA, further supporting a role for ROS. Cells expressing dominant
      negative RhoA failed to endocytose the Na,K-ATPase during hypoxia or after H2O2
      treatment. Na,K-ATPase endocytosis was also prevented in cells treated with Y
      27632, a Rho-associated kinase (ROCK) inhibitor, and in cells expressing dominant
      negative ROCK. In summary, we provide evidence that in human alveolar epithelial
      cells exposed to hypoxia, RhoA/ROCK activation is necessary for Na,K-ATPase
      endocytosis via a mechanism that requires mitochondrial ROS.

PMID- 17550968
TI  - The effect of cellular cholesterol on membrane-cytoskeleton adhesion.
AB  - Whereas recent studies suggest that cholesterol plays important role in the
      regulation of membrane proteins, its effect on the interaction of the cell
      membrane with the underlying cytoskeleton is not well understood. Here, we
      investigated this by measuring the forces needed to extract nanotubes (tethers)
      from the plasma membrane, using atomic force microscopy. The magnitude of these
      forces provided a direct measure of cell stiffness, cell membrane effective
      surface viscosity and association with the underlying cytoskeleton. Furthermore,
      we measured the lateral diffusion constant of a lipid analog DiIC12, using
      fluorescence recovery after photobleaching, which offers additional information
      on the organization of the membrane. We found that cholesterol depletion
      significantly increased the adhesion energy between the membrane and the
      cytoskeleton and decreased the membrane diffusion constant. An increase in
      cellular cholesterol to a level higher than that in control cells led to a
      decrease in the adhesion energy and the membrane surface viscosity. Disassembly
      of the actin network abrogated all the observed effects, suggesting that
      cholesterol affects the mechanical properties of a cell through the underlying
      cytoskeleton. The results of these quantitative studies may help to better
      understand the biomechanical processes accompanying the development of
      atherosclerosis.

PMID- 17550969
TI  - Collagens at a glance.

PMID- 17550970
TI  - The retromer component sorting nexin-1 is required for efficient retrograde
      transport of Shiga toxin from early endosome to the trans Golgi network.
AB  - The mammalian retromer complex is a multi-protein complex that regulates
      retrograde transport of the cation-independent mannose 6-phosphate receptor (CI
      MPR) from early endosomes to the trans Golgi network (TGN). It consists of two
      subcomplexes: a membrane-bound coat comprising sorting nexin-1 (SNX1) and
      possibly sorting nexin-2 (SNX2), and a cargo-selective subcomplex, composed of
      VPS26, VPS29 and VPS35. In addition to the retromer, a variety of other protein
      complexes has been suggested to regulate endosome-to-TGN transport of not only
      the CI-MPR but a wide range of other cargo proteins. Here, we have examined the
      role of SNX1 and SNX2 in endosomal sorting of Shiga and cholera toxins, two
      toxins that undergo endosome-to-TGN transport en route to their cellular targets
      located within the cytosol. By using small interfering RNA (siRNA)-mediated
      silencing combined with single-cell fluorescent-toxin-uptake assays and well
      established biochemical assays to analyze toxin delivery to the TGN, we have
      established that suppression of SNX1 leads to a significant reduction in the
      efficiency of endosome-to-TGN transport of the Shiga toxin B-subunit.
      Furthermore, we show that for the B subunit of cholera toxin, retrograde endosome
      to-TGN transport is less reliant upon SNX1. Overall, our data establish a role
      for SNX1 in the endosome-to-TGN transport of Shiga toxin and are indicative for a
      fundamental difference between endosomal sorting of Shiga and cholera toxins into
      endosome-to-TGN retrograde transport pathways.

PMID- 17550971
TI  - The retromer complex and clathrin define an early endosomal retrograde exit site.
AB  - Previous studies have indicated a role for clathrin, the clathrin adaptors AP1
      and epsinR, and the retromer complex in retrograde sorting from early/recycling
      endosomes to the trans Golgi network (TGN). However, it has remained unclear
      whether these protein machineries function on the same or parallel pathways. We
      show here that clathrin and the retromer subunit Vps26 colocalize at the
      ultrastructural level on early/recycling endosomes containing Shiga toxin B
      subunit, a well-studied retrograde transport cargo. As previously described for
      clathrin, we find that interfering with Vps26 expression inhibits retrograde
      transport of the Shiga toxin B-subunit to the TGN. Under these conditions,
      endosomal tubules that take the Shiga toxin B-subunit out of transferrin
      containing early/recycling endosomes appear to be stabilized. This situation
      differs from that previously described for low-temperature incubation and
      clathrin-depletion conditions under which Shiga toxin B-subunit labeling was
      found to overlap with that of the transferrin receptor. In addition, we find that
      the Shiga toxin B-subunit and the transferrin receptor accumulate close to
      multivesicular endosomes in clathrin-depleted cells, suggesting that clathrin
      initiates retrograde sorting on vacuolar early endosomes, and that retromer is
      then required to process retrograde tubules. Our findings thus establish a role
      for the retromer complex in retrograde transport of the B-subunit of Shiga toxin,
      and strongly suggest that clathrin and retromer function in consecutive
      retrograde sorting steps on early endosomes.

PMID- 17550972
TI  - CTGF enhances the motility of breast cancer cells via an integrin-alphavbeta3
      ERK1/2-dependent S100A4-upregulated pathway.
AB  - Connective tissue growth factor (CTGF) expression is elevated in advanced stages
      of breast cancer, but the regulatory role of CTGF in invasive breast cancer cell
      phenotypes is unclear. Presently, overexpression of CTGF in MCF-7 cells (MCF
      7/CTGF cells) enhanced cellular migratory ability and spindle-like morphological
      alterations, as evidenced by actin polymerization and focal-adhesion-complex
      aggregation. Reducing the CTGF level in MDA-MB-231 (MDA231) cells by antisense
      CTGF cDNA (MDA231/AS cells) impaired cellular migration and promoted a change to
      an epithelial-like morphology. A neutralizing antibody against integrin
      alphavbeta3 significantly attenuated CTGF-mediated ERK1/2 activation and cellular
      migration, indicating that the integrin-alphavbeta3-ERK1/2 signaling pathway is
      crucial in mediating CTGF function. Moreover, the cDNA microarray analysis
      revealed CTGF-mediated regulation of the prometastatic gene S100A4. Transfection
      of MCF-7/CTGF cells with AS-S100A4 reversed the CTGF-induced cellular migratory
      ability, whereas overexpression of S100A4 in MDA231/AS cells restored their high
      migratory ability. Genetic and pharmacological manipulations suggested that the
      CTGF-mediated S100A4 upregulation was dependent on ERK1/2 activation, with
      expression levels of CTGF and S100A4 being closely correlated with human breast
      tumors. We conclude that CTGF plays a crucial role in migratory/invasive
      processes in human breast cancer by a mechanism involving activation of the
      integrin-alphavbeta3-ERK1/2-S100A4 pathway.

PMID- 17550973
TI  - Distinct approaches to investigate the importance of the murine 4-1BB 4-1BBL
      interaction in the antibody response to Streptococcus pneumoniae.
AB  - Protection against infection with Streptococcus pneumoniae is based mainly on the
      generation of antibodies to the pneumococcal capsular polysaccharides (caps-PS).
      Although caps-PS are considered thymus-independent antigens, there is a growing
      body of evidence that T lymphocytes and costimulatory molecules are involved in
      the regulation of the antibody response to caps-PS. We investigated whether the
      interaction between 4-1BB and 4-1BB ligand (4-1BBL) is involved in the modulation
      of the antibody response to caps-PS after immunization with Pneumovax or with
      intact heat-killed S. pneumoniae. Treatment with agonistic anti-4-1BB mAb, which
      mimics engagement of 4-1BB by 4-1BBL, had no effect on the IgG and IgM immune
      response to caps-PS (Serotype 3) after immunization with Pneumovax or with S.
      pneumoniae Serotype 3. However, anti-4-1BB treatment strongly inhibited the IgG
      response to pneumococcal surface protein A (PspA). By contrast, the IgG anti-caps
      PS (Serotype 3) antibody response was reduced strongly in 4-1BBL(-/-) mice
      immunized with S. pneumoniae Serotype 3. The IgG anti-PspA antibody response in
      the 4-1BB(-/-) mice was comparable with the immune response in the wild-type
      mice. We conclude that distinct pathways are involved in the humoral antibody
      response to pneumococcal antigens, depending on the nature of the antigen and the
      context in which the different antigens are presented. The 4-1BB-4-1BBL
      interaction is not involved in the antibody response to soluble caps-PS. The
      influence of the 4-1BB-4-1BBL interaction in the immune reaction to S. pneumoniae
      Serotype 3 depends on the experimental system used.

PMID- 17550974
TI  - Fibrocytes in lung disease.
AB  - Fibrocytes were first described over a decade ago as a population of cells in
      circulation with fibroblast-like properties, which were involved in tissue
      repair. Since that time, we have learned a significant amount about these bone
      marrow-derived cells, which contribute to wound healing and fibrosis. Fibrocytes
      express leukocyte markers such as CD34, CD45, and CD13 and also express
      mesenchymal markers such as pro-collagens I and III, vimentin, and fibronectin.
      In addition, they have been shown to express the chemokine receptors CXCR4 and
      CCR7, which appear to be important in cellular trafficking from the vascular to
      the extravascular compartment. Fibrocytes have been shown to contribute to a
      number of fibrotic disorders, and here, we review their involvement in lung
      diseases including pulmonary fibrosis, asthma, and vascular remodeling.

PMID- 17550975
TI  - Fibrinogen is localized on dark zone follicular dendritic cells in vivo and
      enhances the proliferation and survival of a centroblastic cell line in vitro.
AB  - Follicular dendritic cells (FDC) in the germinal centers (GC) of secondary
      lymphoid organs increase the survival and proliferation of antigen-stimulated B
      cells and are pivotal for the affinity maturation of an antibody response and for
      maintenance of B cell immunological memory. The dark zone (DZ) and the light zone
      (LZ) constitute distinct areas of the GC containing different subtypes of FDC as
      identified by their morphology and phenotype. Until now, most available FDC
      specific reagents identify LZ FDC, and there are no reagents recognizing DZ FDC
      specifically. Here, we report a new mAb, D46, which stains FDC specifically in
      the DZ of bovine and ovine GC within the secondary follicles. We identify its
      ligand as bovine fibrinogen, and using commercially available anti-human
      fibrinogen antibodies, show that this inflammatory protein is also present on DZ
      FDC of human GC within palatine tonsils. In vitro, the addition of exogenous
      fibrinogen stimulates the proliferation and survival of BCR-stimulated L3055
      cells, which constitute a clonal population of centroblastic cells and retain
      important features of normal GC B cells. Together, our results suggest that
      fibrinogen localized on DZ FDC could support the extensive proliferation and
      survival of GC B cells within the DZ in vivo.

PMID- 17550976
TI  - Coactivation of janus tyrosine kinase (Jak)1 positively modulates prolactin-Jak2
      signaling in breast cancer: recruitment of ERK and signal transducer and
      activator of transcription (Stat)3 and enhancement of Akt and Stat5a/b pathways.
AB  - Prolactin (PRL) receptors (PRLRs) have been considered selective activators of
      Janus tyrosine kinase (Jak)2 but not Jak1, Jak3, or Tyk2. We now report marked
      PRL-induced tyrosine phosphorylation of Jak1, in addition to Jak2, in a series of
      human breast cancer cell lines, including T47D, MCF7, and SKBR3. In contrast, PRL
      did not activate Jak1 in immortalized, noncancerous breast epithelial lines HC11,
      MCF10A, ME16C, and HBL-100, or in CWR22Rv1 prostate cancer cells or MDA-MB-231
      breast cancer cells. However, introduction of exogenous PRLR into MCF10A, ME16C,
      or MDA-MB-231 cells reconstituted both PRL-Jak1 and PRL-Jak2 signals. In vitro
      kinase assays verified that PRL stimulated enzymatic activity of Jak1 in T47D
      cells, and PRL activated Jak1 and Jak2 with indistinguishable time and dose
      kinetics. Relative Jak2 deficiency did not cause PRLR activation of Jak1, because
      overexpression of Jak2 did not interfere with PRL activation of Jak1. Instead,
      PRL activated Jak1 through a Jak2-dependent mechanism, based on disruption of PRL
      activation of Jak1 after Jak2 suppression by 1) lentiviral delivery of Jak2 short
      hairpin RNA, 2) adenoviral delivery of dominant-negative Jak2, and 3) AG490
      pharmacological inhibition. Finally, suppression of Jak1 by lentiviral delivery
      of Jak1 short hairpin RNA blocked PRL activation of ERK and signal transducer and
      activator of transcription (Stat)3 and suppressed PRL activation of Jak2, Stat5a,
      Stat5b, and Akt, as well as tyrosine phosphorylation of PRLR. The data suggest
      that PRL activation of Jak1 represents a novel, Jak2-dependent mechanism that may
      serve as a regulatory switch leading to PRL activation of ERK and Stat3 pathways,
      while also serving to enhance PRL-induced Stat5a/b and Akt signaling.

PMID- 17550977
TI  - Nur77 coordinately regulates expression of genes linked to glucose metabolism in
      skeletal muscle.
AB  - Innervation is important for normal metabolism in skeletal muscle, including
      insulin-sensitive glucose uptake. However, the transcription factors that
      transduce signals from the neuromuscular junction to the nucleus and affect
      changes in metabolic gene expression are not well defined. We demonstrate here
      that the orphan nuclear receptor Nur77 is a regulator of gene expression linked
      to glucose utilization in muscle. In vivo, Nur77 is preferentially expressed in
      glycolytic compared with oxidative muscle and is responsive to beta-adrenergic
      stimulation. Denervation of rat muscle compromises expression of Nur77 in
      parallel with that of numerous genes linked to glucose metabolism, including
      glucose transporter 4 and genes involved in glycolysis, glycogenolysis, and the
      glycerophosphate shuttle. Ectopic expression of Nur77, either in rat muscle or in
      C2C12 muscle cells, induces expression of a highly overlapping set of genes,
      including glucose transporter 4, muscle phosphofructokinase, and glycogen
      phosphorylase. Furthermore, selective knockdown of Nur77 in rat muscle by small
      hairpin RNA or genetic deletion of Nur77 in mice reduces the expression of a
      battery of genes involved in skeletal muscle glucose utilization in vivo.
      Finally, we show that Nur77 binds the promoter regions of multiple genes involved
      in glucose metabolism in muscle. These results identify Nur77 as a potential
      mediator of neuromuscular signaling in the control of metabolic gene expression.

PMID- 17550978
TI  - Metabolomic and genetic analysis of biomarkers for peroxisome proliferator
      activated receptor alpha expression and activation.
AB  - Peroxisome proliferator-activated receptor alpha (PPARalpha) is a nuclear
      receptor with manifold effects on intermediary metabolism. To define a set of
      urinary biomarkers that could be used to determine the efficacy of PPARalpha
      agonists, a metabolomic investigation was undertaken in wild-type and Pparalpha
      null mice fed for 2 wk either a regular diet or a diet containing the PPARalpha
      ligand Wy-14,643 ([4-chloro-6-(2,3-xylidino)-2-pyrimidinylthio] acetic acid), and
      their urine was analyzed by ultra-performance liquid chromatography coupled with
      time-of-flight mass spectrometry. Principal components analysis of 6393 accurate
      mass positive ions revealed clustering as a single phenotype of the treated and
      untreated Pparalpha (-/-) mice plus two additional discrete phenotypes for the
      treated and untreated Pparalpha (+/+) mice. Biomarkers of PPARalpha activation
      were identified from their accurate masses and confirmed by tandem mass
      spectrometry of authentic compounds. Biomarkers were quantitated from raw
      chromatographic data using appropriate calibration curves. PPARalpha urinary
      biomarkers highly statistically significantly elevated by Wy-14,643 treatment
      included 11beta-hydroxy-3,20-dioxopregn-4-en-21-oic acid (>3700-fold), 11beta,20
      dihydroxy-3-oxopregn-4-en-21-oic acid (50-fold), nicotinamide (>2-fold),
      nicotinamide 1-oxide (5-fold), 1-methylnicotinamide (1.5-fold), hippuric acid (2
      fold), and 2,8-dihydroxyquinoline-beta-d-glucuronide (3-fold). PPARalpha urinary
      biomarkers highly statistically significantly attenuated by Wy-14,643 treatment
      included xanthurenic acid (1.3-fold), hexanoylglycine (20-fold),
      phenylpropionylglycine (4-fold), and cinnamoylglycine (9-fold). These biomarkers
      arise from PPARalpha effects on tryptophan, corticosterone, and fatty acid
      metabolism and on glucuronidation. This study underscores the power of mass
      spectrometry-based metabolomics combined with genetically modified mice in the
      definition of monogenic metabolic phenotypes.

PMID- 17550979
TI  - Ribonucleic acid binding protein-mediated regulation of luteinizing hormone
      receptor expression in granulosa cells: relationship to sterol metabolism.
AB  - Posttranscriptional mechanism plays a crucial role in regulating LH receptor
      (LHR) expression in the ovary. We have identified a novel trans-factor, LHR mRNA
      binding protein (LRBP), which binds to a polypyrimidine-rich bipartite sequence
      of the coding region of LHR mRNA, and its identity was established as mevalonate
      kinase (Mvk). Although an inverse relation between LHR mRNA expression and RNA
      binding activity of LRBP has been established, its intermediary role in LHR mRNA
      expression has not been demonstrated. The present study examined the direct role
      of Mvk in regulating LHR expression by using primary cultures of human granulosa
      cells as a model system. A marked decrease in LHR mRNA stability and an increase
      in Mvk expression were seen when cultured granulosa cells were treated with human
      chorionic gonadotropin (hCG) in vitro. This treatment also resulted in an
      increase in LHR mRNA binding activity in the cytosolic fractions prepared from
      hCG-treated cells compared with the control. Because Mvk expression is regulated
      by sterol response element-binding protein-1, which is sensitive to the cellular
      concentration of 25-hydroxycholesterol (25-OHC), cultured granulosa cells were
      treated with this oxysterol, and the expression of Mvk gene was examined. As
      expected, treatment with 25-OHC inhibited the Mvk (LRBP) expression, as well as
      the LHR mRNA binding activity of LRBP. To determine the role of Mvk in ligand
      mediated down-regulation of LHR mRNA, cells were additionally treated with 25-OHC
      when treated with hCG. The results showed that the decrease in Mvk expression by
      oxysterol treatment abrogated ligand-induced down-regulation of LHR mRNA. These
      results therefore establish a direct participation of Mvk in regulating LHR
      expression and suggest a novel relationship between cholesterol metabolism and
      LHR expression in the ovary.

PMID- 17550980
TI  - Matching receptome genes with their ligands for surveying paracrine/autocrine
      signaling systems.
AB  - Sequencing of genomes from diverse organisms facilitates studies on the
      repertoire of genes involved in intercellular signaling. Extending previous
      efforts to annotate most human plasma membrane receptors in the Human Plasma
      Membrane Receptome database, we matched cognate ligands with individual receptors
      by surveying the published literature. In the updated online database we called
      "liganded receptome," users can search for individual ligands or receptors to
      reveal their pairing partners and browse through receptor or ligand families to
      identify relationships between ligands and receptors in their respective
      families. Because local signaling systems are prevalent in diverse normal and
      diseased tissues, we used the liganded receptome knowledgebase to interrogate DNA
      microarray datasets for genome-wide analyses of potential paracrine/autocrine
      signaling systems. In addition to viewing ligand-receptor coexpression based on
      precomputed DNA microarray data, users can submit their own microarray data to
      perform online genome-wide searches for putative paracrine/autocrine signaling
      systems. Investigation of transcriptome data based on liganded receptome allows
      the discovery of paracrine/autocrine signaling for known ligand-receptor pairs in
      previously uncharacterized tissues or developmental stages. The present
      annotation of ligand-receptor pairs also identifies orphan receptors and ligands
      without known interacting partners in select families. Because hormonal ligands
      within the same family usually interact with paralogous receptors, this genomic
      approach could also facilitate matching of orphan receptors and ligands. The
      liganded receptome is accessible at http://receptome.stanford.edu.

PMID- 17550981
TI  - The zinc finger protein ras-responsive element binding protein-1 is a coregulator
      of the androgen receptor: implications for the role of the Ras pathway in
      enhancing androgenic signaling in prostate cancer.
AB  - Androgen receptor (AR) plays an important role in normal prostate function as
      well as in the etiology of prostate cancer. Activation of AR is dictated by
      hormone binding and by interactions with coregulators. Several of these
      coregulators are known targets of Ras-related signals. Recent evidence suggests
      that Ras activation may play a causal role in the progression of prostate cancer
      toward a more malignant and hormone-insensitive phenotype. In the present study,
      we used a transcription factor-transcription factor interaction array method to
      identify the zinc finger protein Ras-responsive element binding protein (RREB-1)
      as a partner and coregulator of AR. In LNCaP prostate cancer cells, RREB-1 was
      found to be present in a complex with endogenous AR as determined by
      coimmunoprecipitation, glutathione S-transferase pull down, and
      immunofluorescence analyses. RREB-1 bound to the prostate-specific antigen (PSA)
      promoter as assessed by chromatin immunoprecipitation. Transient expression of
      RREB-1 down-regulated AR-mediated promoter activity and suppressed expression of
      PSA protein. The repressor activity of RREB-1 was significantly attenuated by
      cotransfection of activated Ras. Moreover, expression of the dominant-negative N
      17-Ras or, alternatively, use of the MAPK kinase inhibitor PD98059 [2-(2-amino-3
      methyoxyphenyl)-4H-1-benzopyran-4-one] abolished the effect of Ras in attenuating
      RREB-1-mediated repression. Furthermore, inhibition of RREB-1 expression by RNA
      interference enhanced the effect of Ras on PSA promoter activity and PSA
      expression. In addition, activation of the Ras pathway depleted AR from the RREB
      1/AR complex. Collectively, our data for the first time identify RREB-1 as a
      repressor of AR and further implicate the Ras/MAPK kinase pathway as a likely
      antagonist of the inhibitory effects of RREB-1 on androgenic signaling.

PMID- 17550982
TI  - Estrogen-regulated gene networks in human breast cancer cells: involvement of
      E2F1 in the regulation of cell proliferation.
AB  - Estrogens generally stimulate the proliferation of estrogen receptor (ER)
      containing breast cancer cells, but they also suppress proliferation of some ER
      positive breast tumors. Using a genome-wide analysis of gene expression in two ER
      positive human breast cancer cell lines that differ in their proliferative
      response to estrogen, we sought to identify genes involved in estrogen-regulated
      cell proliferation. To this end, we compared the transcriptional profiles of MCF
      7 and MDA-MB-231ER+ cells, which have directionally opposite 17beta-estradiol
      (E2)-dependent proliferation patterns, MCF-7 cells being stimulated and 231ER+
      cells suppressed by E2. We identified a set of approximately 70 genes regulated
      by E2 in both cells, with most being regulated by hormone in an opposite fashion.
      Using a variety of bioinformatics approaches, we found the E2F binding site to be
      overrepresented in the potential regulatory regions of many cell cycle-related
      genes stimulated by estrogen in MCF-7 but inhibited by estrogen in 231ER+ cells.
      Biochemical analyses confirmed that E2F1 and E2F downstream target genes were
      increased in MCF-7 and decreased in 231ER+ cells upon estrogen treatment.
      Furthermore, RNA interference-mediated knockdown of E2F1 blocked estrogen
      regulation of E2F1 target genes and resulted in loss of estrogen regulation of
      proliferation. These results demonstrate that regulation by estrogen of E2F1, and
      subsequently its downstream target genes, is critical for hormone regulation of
      the proliferative program of these breast cancer cells, and that gene expression
      profiling combined with bioinformatic analyses of transcription factor binding
      site enrichment in regulated genes can identify key components associated with
      nuclear receptor hormonal regulation of important cellular functions.

PMID- 17550983
TI  - Stromal cell-derived factor-1 induces matrix metalloprotease-13 expression in
      human chondrocytes.
AB  - The production of chemokine stromal cell-derived factor (SDF)-1 is significantly
      higher in synovial fluid of patients with osteoarthritis and rheumatoid
      arthritis. Matrix metalloproteinase (MMP)-13 may contribute to the breakdown of
      articular cartilage during arthritis. Here, we found that SDF-1alpha increased
      the secretion of MMP-13 in cultured human chondrocytes, as shown by reverse
      transcriptase-polymerase chain reaction, Western blot, and zymographic analysis.
      SDF-1alpha also increased the surface expression of CXCR4 receptor in human
      chondrocytes. CXCR4-neutralizing antibody, CXCR4-specific inhibitor [1-[[4
      (1,4,8,11-tetrazacyclotetradec-1-ylmethyl)phenyl]methyl]-1,4,8,11
      tetrazacyclotetradecane (AMD3100)], or small interfering RNA against CXCR4
      inhibited the SDF-1alpha-induced increase of MMP-13 expression. The
      transcriptional regulation of MMP-13 by SDF-1alpha was mediated by
      phosphorylation of extracellular signal-regulated kinases (ERK) and activation of
      the activator protein (AP)-1 components of c-Fos and c-Jun. The binding of c-Fos
      and c-Jun to the activator protein (AP-1) element on the MMP-13 promoter and the
      increase in luciferase activity was enhanced by SDF-1alpha. Cotransfection with
      dominant-negative mutant of ERK2 or c-Fos and c-Jun antisense oligonucleotide
      inhibited the potentiating action of SDF-1alpha on MMP-13 promoter activity.
      Taken together, our results provide evidence that SDF-1alpha acts through CXCR4
      to activate ERK and the downstream transcription factors (c-Fos and c-Jun),
      resulting in the activation of AP-1 on the MMP-13 promoter and contributing
      cartilage destruction during arthritis.

PMID- 17550984
TI  - Signaling pathways involved in cyclooxygenase-2 induction by hepatocyte growth
      factor in non small-cell lung cancer.
AB  - Many studies have suggested a role for the hepatocyte growth factor (HGF)/c-Met
      pathway in tumorigenesis. Some actions of HGF are believed to be mediated by
      cyclooxygenase-2 (COX-2), resulting in the production of prostaglandin E2
      (PGE(2)). We examined four c-Met-positive non-small-cell lung cancer (NSCLC) cell
      lines for effects of HGF on COX-2. HGF increased COX-2 protein expression 3-fold
      over basal levels. Induction of COX-2 occurred through both the extracellular
      signal-regulated kinase 1/2 and p38 pathways. HGF treatment caused activation of
      the activator protein-1, CCAAT/enhancer-binding protein, and cAMP response
      element-binding protein transcription factors, and COX-2 induction was blocked by
      actinomycin D. The half-life of COX-2 mRNA was also increased by HGF. HGF
      stimulation resulted in a 4-fold increase in PGE(2) secretion, and treatment of
      NSCLC cells with exogenous PGE(2) significantly increased cell proliferation. The
      addition of PGE(2) to NSCLC cells also led to rapid phosphorylation of c-Met in
      the absence of HGF, which was blocked by epidermal growth factor receptor (EGFR)
      inhibition. EGFR ligands were released in response to PGE(2). This suggests that
      secretion of PGE(2) induced by HGF/c-Met pathway activation can further activate
      the c-Met pathway via EGFR in a reinforcing loop that is independent of HGF. HGF
      and PGE(2) each significantly stimulated invasion in NSCLC cells. Cells
      transiently transfected with c-Met antisense plasmid showed a significant
      decrease in HGF- or PGE(2)-induced invasion. PGE(2)-induced invasion was EGFR
      dependent, confirming a link between PGE(2), EGFR, and c-Met. Targeting of both
      the HGF/c-Met and PGE(2) pathways with a neutralizing antibody to HGF and
      celecoxib resulted in enhanced anti-invasion effects in response to HGF.

PMID- 17550985
TI  - A genome scan in a single pedigree with a high prevalence of multiple sclerosis.
AB  - BACKGROUND: Multiple sclerosis (MS) is a disease that is widely believed to be
      autoimmune in nature. Genetic-epidemiological studies implicate susceptibility
      genes in the pathogenesis of MS, although non-MHC susceptibility linkages have
      been difficult to confirm. Insight into pathways that are intrinsic to other
      complex diseases has come from the genetic analysis of large, autosomal-dominant
      kindreds. Here, we present a genetic study of a large and unique kindred in which
      MS appears to follow an autosomal-dominant pattern of inheritance, with
      consistent penetrance in four generations. METHODS: Eighty-two individuals of
      this 370-member family were genotyped with 681 microsatellite markers spanning
      the genome, with an average spacing of 5.3 cM. RESULTS: Parametric linkage
      analysis was performed and no significant LOD score (LOD >3.3) was observed. For
      a rare dominant disease model with reduced penetrance, 99.6% of the genome was
      excluded at a LOD score <-1 and 96% at a LOD score <-2. The HLA-DRB1 candidate
      gene was also genotyped by allele-specific methods. In each instance where at
      least one parent was positive for HLA-DRB1*15, one or more HLA-DRB1*15 alleles
      were transmitted to the affected offspring (11/11). HLA-DRB1*15 was transmitted
      equally from both the familial and the married-in parents and therefore this
      locus does not appear to be an autosomal-dominant acting gene in this family but
      an important modifier of risk. CONCLUSIONS: These results further stress the
      importance of the HLA-DRB1*15-bearing haplotype in determining MS susceptibility.
      Furthermore, this study highlights the complexity of MS genetics, even in the
      presence of a single family, seemingly segregating MS as an autosomal-dominant
      trait.

PMID- 17550986
TI  - The usefulness of clinical findings in localising lesions in Bell's palsy:
      comparison with MRI.
AB  - BACKGROUND: Although electrophysiological tests and brain MRI provide information
      about the site of the lesion in Bell's palsy, clinicians usually depend on
      clinical data. However, the accuracy of clinical findings in identifying lesions
      has never been evaluated. METHOD: A total of 57 patients with idiopathic
      peripheral facial palsy were included in this study. We determined the sites of
      the lesions based on associated symptoms and by brain MRI. We then compared the
      two to assess the value of clinical findings in determining lesion sites.
      RESULTS: Of the 57 patients, 27 were men. The mean age of all patients was 50.6+/
      16.7 years. The lesion sites determined from clinical findings were as follows:
      the infrageniculate-suprastapedial segment, 13 (23%); the infrastapedial
      suprachordal segment, 9 (16%); and the mastoid segment, 35 (61%). No sites were
      classified as involving the suprageniculate segment. On brain MRI, 51 (89%) of
      the 57 patients showed abnormal enhancement of the facial nerve, with the most
      common area being the suprageniculate segment, including the distal intrameatal,
      labyrinthine and geniculate ganglion. CONCLUSIONS: We demonstrate that clinical
      history is not helpful in determining the site of a lesion in Bell's palsy. The
      segment most frequently involved in Bell's palsy is the suprageniculate segment.

PMID- 17550987
TI  - Evolution of different MRI measures in patients with active relapsing-remitting
      multiple sclerosis over 2 and 5 years: a case-control study.
AB  - BACKGROUND: There is growing evidence for the concept of multiple sclerosis (MS)
      as an inflammatory neurodegenerative disease, with a different pattern of atrophy
      evolution in grey matter (GM) and white matter (WM) tissue compartments.
      OBJECTIVE: We aimed to investigate the evolution of different MRI measures in
      early relapsing-remitting patients with MS and in normal controls (NCs) over 2
      years. We also evaluated the progression of these MRI measures in a subset of
      patients who were followed for up to 5 years. METHODS: Included in this study
      were 147 patients who participated in the combination ASA (Avonex Steroids
      Azathioprine) study and completed full treatment, clinical and MRI assessment at
      0, 12 and 24 months. A subgroup of 66 patients was followed for 36 months, 51
      patients for 48 months and 43 patients for 60 months. Mean age at baseline was
      30.7 years, mean disease duration was 5.5 years, mean EDSS was 1.8 and mean
      annualised relapse rate before study entry was 1.7. MRI scans were performed on a
      1.5T scanner every 2 months for the first 2 years and thereafter once yearly for
      up to 5 years. In addition to the MS group, 27 NCs were examined at months 0, 12
      and 24 using the same MRI protocol. Percentage brain volume change (PBVC), GM
      volume (GMV), WM volume (WMV) and peripheral grey volume (PGV) were measured
      annually using SIENA/X software. T2-hyperintense lesion volume (LV), lateral
      ventricle volume (LVV) and third ventricle width (3VW) were also assessed
      annually. RESULTS: Over the period of 0-24 months, patients with MS lost
      significantly more GMV (-2.6% vs -0.72%, p<0.001), PGV (-2.4% vs -1.03%, p<0.001)
      and PBVC (-1.2% vs -0.22%, p<0.001), and increased in LVV (+16.6% vs +0.55%,
      p<0.003) and 3VW (+9.3% vs 0%, p = 0.003), when compared with NCs. Within-person
      change in MRI measures for patients with MS over 5 years was -4.2% for PBVC, 
      6.2% for GMV, -5.8% for PGV, -0.5% for WMV (all p<0.001), +68.7 for LVV
      (p<0.001), +4% for 3VW (p<0.001) and +42% for T2-LV (p<0.001). CONCLUSIONS: Our
      study confirmed a different pattern of GM, WM and central atrophy progression
      over 2 years between patients with MS and NCs. The study showed a different
      evolution of tissue compartment atrophy measures in patients with MS, with faster
      decline in cortical and deep GM regions, as well as periventricular WM regions,
      over a 5-year period.

PMID- 17550988
TI  - Diffusion weighted imaging in ataxic hemiparesis.
AB  - OBJECTIVE: Ataxic hemiparesis (AH) is a well recognised lacunar syndrome
      involving homolateral ataxia with accompanying corticospinal tract impairment.
      Most previous studies of lesion location in AH did not use diffusion weighted MRI
      (DW MRI). The purpose of this study was to use DW MRI to evaluate the
      radiological correlation in patients presenting with AH. METHODS:
      Retrospectively, we studied 29 patients with AH using DW MRI. RESULTS: All
      patients were scanned within 4 days of onset. Acute infarction was identified in
      28 of 29 (97%) patients. A single lesion was identified in 26 PATIENTS: pons (n =
      8), internal capsule (n = 6), corona radiata (n = 2), distended internal capsule
      from corona radiate (n = 7), frontal subcortical area (n = 1) and precentral with
      or without postcentral gyrus (n = 2). Two lesions were found in two patients: in
      the pons and corpus callosum of one patient, and in the corona radiata and
      subcortical white matter of the other. CONCLUSIONS: AH is mainly caused by
      pontine or internal capsule/corona radiata lesions. It also occurs in the
      precentral gyrus, including the precentral knob, with or without postcentral
      gyrus lesions. Fibres of the fronto-ponto-cerebellar system may originate from
      the frontal cortex, including the precentral gyrus, probably near the pyramidal
      tract. Damage at this location may cause AH.

PMID- 17550989
TI  - Trading death and disability in malignant stroke.

PMID- 17550990
TI  - Multiple mitochondrial DNA deletions in monozygotic twins with OPMD.
AB  - BACKGROUND: Oculopharyngeal muscular dystrophy (OPMD) is caused by expansions of
      the poly (A) binding protein 2 (PABP2) gene. Previous histological analyses have
      revealed mitochondrial abnormalities in the muscles of OPMD patients but their
      significance remains uncertain. OBJECTIVE: We had the rare opportunity to study
      monozygotic twins with identical expansions of the PABP2 gene but with markedly
      different severities of OPMD. Both had histological features of mitochondrial
      myopathy. We determined whether mitochondrial DNA abnormalities underlay these
      changes. METHODS: Clinical information was obtained by history and examination.
      Muscle biopsies were obtained from each subject and genetic analysis was
      performed using long-range PCR and Southern blotting. RESULTS: We demonstrate,
      for the first time, the presence of mitochondrial DNA (mtDNA) deletions by
      Southern blotting in individuals with OPMD. This correlates with the presence of
      mitochondrial myopathy in both twins. Moreover, both twins had different mtDNA
      deletions, which might explain their phenotypic differences. CONCLUSION: We
      hypothesise that mitochondrial dysfunction may occur as a consequence of PABP2
      gene mutations, and that this dysfunction may affect the phenotypic
      manifestations of OPMD.

PMID- 17550991
TI  - Analysis of survival and prognostic factors in amyotrophic lateral sclerosis: a
      population based study.
AB  - OBJECTIVE: To measure survivorship and predictors of prognosis of amyotrophic
      lateral sclerosis (ALS). METHODS: Incident cases, diagnosed in the 1998-1999
      period and classified according to the El Escorial criteria, were enrolled from a
      prospective population based registry established in Puglia, Southern Italy, with
      a reference population of 4,025,329. Cases were followed up until death or 30
      June 2004. RESULTS: We identified 130 incident cases of ALS while four were lost
      to follow-up. Median survival was 28 months from first symptoms and 16 months
      from diagnosis, while cumulative survivorship at 4 years was approximately 30%.
      Advanced age (>75 years: hazard ratio (HR) 7.5; 95% CI 1.9 to 29.6; p = 0.004)
      and bulbar or generalised (HR 1.8; 95% CI 1.1 to 3.0; p = 0.01) onset of symptoms
      were independent predictors of adverse survival. After stratifying patients
      according to site of first symptoms, age was a predictor of death among spinal
      (HR for patients aged >75 years compared with patients aged 45 years or less: HR
      11; 95% CI 1.5 to 78.5; p = 0.01) but not among bulbar ALS (HR 4.5; 95% CI 0.4 to
      46.5; p = 0.2). Among spinal onset cases, cases with predominant upper
      motoneuronal (UMN) involvement presented with a borderline significant better
      survivorship (HR 0.5; 95% CI 0.2 to 1.3; p = 0.1) CONCLUSIONS: Bulbar signs and
      advanced age among subjects with spinal onset were indicators of poor prognosis
      while El Escorial category at entry did not predict survival. Among subjects with
      spinal onset of the disease, a trend for a better survivorship of subjects with
      UMN signs was noted.

PMID- 17550992
TI  - Complications following sural and peroneal nerve biopsies.
AB  - Nerve biopsy is used as part of the investigation of patients with peripheral
      neuropathy and is particularly useful in confirming the diagnosis of peripheral
      nerve vasculitis. Previous studies have suggested that sampling the peroneal
      nerve, in combination with peroneus brevis, is more sensitive than the sural
      nerve for this diagnosis but there are no published data on the complication rate
      of peroneal nerve biopsies. We have assessed the complications in 50 patients
      undergoing nerve biopsy, and have shown that although biopsy of the peroneal
      nerve may result in a larger area of sensory loss in some patients, other
      complications are not increased when compared with sural nerve biopsy.

PMID- 17550993
TI  - Abundance of dinucleotide repeats and gene expression are inversely correlated: a
      role for gene function in addition to intron length.
AB  - High and broad transcription of eukaryotic genes is facilitated by cost
      minimization, clustered localization in the genome, elevated G+C content, and low
      nucleosome formation potential. In this scenario, illumination of correlation
      between abundance of (TG/CA)(n>or=12) repeats, which are negative cis modulators
      of transcription, and transcriptional levels and other commonly occurring
      dinucleotide repeats, is required. Three independent microarray datasets were
      used to examine the correlation of (TG/CA)(n>or=12) and other dinucleotide
      repeats with gene expression. Compared with the expected equi-distribution
      pattern under neutral model, highly transcribed genes were poor in repeats, and
      conversely, weakly transcribed genes were rich in repeats. Furthermore, the
      inverse correlation between repeat abundance and transcriptional levels appears
      to be a global phenomenon encompassing all genes regardless of their breadth of
      transcription. This selective pattern of exclusion of (TG/CA)(n>or=12) and
      (AT)(n>or=12) repeats in highly transcribed genes is an additional factor along
      with cost minimization and elevated GC, and therefore, multiple factors govern
      high transcription of genes. We observed that even after controlling for the
      effects of GC and average intron lengths, the effect of repeats albeit somewhat
      weaker was persistent and definite. In the ribosomal protein coding genes,
      sequence analysis of orthologs suggests that negative selection for repeats
      perhaps occurred early in evolution. These observations suggest that negative
      selection of (TG/CA)(n>or=12) microsatellites in the evolution of the highly
      expressed genes was also controlled by gene function in addition to intron
      length.

PMID- 17550995
TI  - Gene expression analysis illuminates the transcriptional programs underlying the
      functional activity of ex vivo-expanded granulocytes.
AB  - Global gene expression analysis established the temporal expression patterns and
      programs underlying the development of functional activity of ex vivo-expanded
      (EXE) human granulocytes, as well as differences compared with peripheral blood
      (PB) granulocytes. CD34(+) progenitor cells were cultured for 3 wk to induce
      rapid expansion and granulocytic differentiation, with 40% CD15(+) cells by day 3
      and 90% by day 12. Phagocytic and respiratory burst activity increased with the
      fraction of CD15(++)CD11b(+) cells (myelocytes to segmented) and peaked by day
      17. However, only 25% of CD15(++)CD11b(+) cells were phagocytic, and respiratory
      burst activity was one-third that of PB granulocytes. EXE granulocytes from later
      days and PB granulocytes showed similar expression of Fc gamma receptors (-1A, 
      2A, -2C, -3A) and complement receptors (-1, -3, -4). Later downregulation of CD36
      (expressed by macrophages) suggests lineage plasticity early in granulocytic
      differentiation. Expression in mature EXE and PB granulocytes was similar for
      most Fc gamma receptor-mediated phagocytosis signaling proteins, including high
      level expression of Hck, Fgr, and the actin-related protein 2/3 complex. Lower
      expression of Lyn, Cdc42, pleckstrin, and PKC beta(I) by EXE granulocytes may
      explain decreased phagocytosis. PB and mature EXE granulocytes expressed similar
      levels of NADPH oxidase complex genes and receptors for fMLP-mediated respiratory
      burst. Lower burst activity by EXE granulocytes may result from lower expression
      of Raf1 and PKC zeta. Elevated expression of toll-like receptor (TLR)2, TLR1, and
      CD14 in mature EXE and PB granulocytes supports a role for the TLR2 and CD14
      pathway in zymosan-mediated respiratory burst activity. Lower activity in EXE
      granulocytes may be due to greater expression of IRAK3, which inhibits TLR
      mediated signaling.

PMID- 17550994
TI  - Identification of the circadian transcriptome in adult mouse skeletal muscle.
AB  - Circadian rhythms are approximate 24-h behavioral and physiological cycles that
      function to prepare an organism for daily environmental changes. The basic clock
      mechanism is a network of transcriptional-translational feedback loops that drive
      rhythmic expression of genes over a 24-h period. The objectives of this study
      were to identify transcripts with a circadian pattern of expression in adult
      skeletal muscle and to determine the effect of the Clock mutation on gene
      expression. Expression profiling on muscle samples collected every 4 h for 48 h
      was performed. Using COSOPT, we identified a total of 215 transcripts as having a
      circadian pattern of expression. Real-time PCR results verified the circadian
      expression of the core clock genes, Bmal1, Per2, and Cry2. Annotation revealed
      cycling genes were involved in a range of biological processes including
      transcription, lipid metabolism, protein degradation, ion transport, and
      vesicular trafficking. The tissue specificity of the skeletal muscle circadian
      transcriptome was highlighted by the presence of known muscle-specific genes such
      as Myod1, Ucp3, Atrogin1 (Fbxo32), and Myh1 (myosin heavy chain IIX). Expression
      profiling was also performed on muscle from the Clock mutant mouse and sarcomeric
      genes such as actin and titin, and many mitochondrial genes were significantly
      downregulated in the muscle of Clock mutant mice. Defining the circadian
      transcriptome in adult skeletal muscle and identifying the significant
      alterations in gene expression that occur in muscle of the Clock mutant mouse
      provide the basis for understanding the role of circadian rhythms in the daily
      maintenance of skeletal muscle.

PMID- 17550996
TI  - Fgl2 deficiency causes neonatal death and cardiac dysfunction during embryonic
      and postnatal development in mice.
AB  - We hypothesized that cardiac dysfunction was responsible for the high perinatal
      lethality that we previously reported in fibrinogen-like protein 2 (Fgl2)
      knockout (KO) mice. We therefore used ultrasound biomicroscopy to assess left
      ventricular (LV) cardiac structure and function during development in Fgl2 KO and
      wild-type (WT) mice. The only deaths observed between embryonic day (E)8.5 (onset
      of heart beating) and postnatal day (P)28 (weaning) were within 3 days after
      birth, when 33% of Fgl2 KO pups died. Histopathology and Doppler assessments
      suggested that death was due to acute congestive cardiac failure without evidence
      of valvular or other obvious cardiac structural abnormalities. Heart rates in
      Fgl2 KO embryos were significantly reduced at E8.5 and E17.5, and irregular heart
      rhythms were significantly more common in Fgl2 KO (21/26) than WT (2/21) embryos
      at E13.5. Indexes of systolic and/or diastolic cardiac function were also
      abnormal in KO mice at E13.5 and E17.5, in postnatal mice studied at P1, and in
      KO mice surviving to P28. M-mode analysis showed no difference in LV diastolic
      chamber dimension, although posterior wall thickness was thinner at P7 and P28 in
      Fgl2 KO mice. We conclude that Fgl2 deficiency is not associated with obvious
      structural cardiac defects but is associated with a high incidence of neonatal
      death as well as contractile dysfunction and rhythm abnormalities during
      embryonic and postnatal development in mice.

PMID- 17550997
TI  - Ubiquitin proteasome pathway gene expression varies in rhesus monkey oocytes and
      embryos of different developmental potential.
AB  - Protein degradation via the ubiquitin-proteasome pathway (UPP) plays a key role
      in diverse aspects of cell physiology and development. In the early embryo, the
      UPP may play an important role in the transition from maternal to embryonic
      control of development. Disruptions in the UPP could thus compromise embryo
      developmental potential. Additionally, species-specific requirements may dictate
      diverse patterns of regulation of the UPP components. To investigate the
      expression of UPP components in a nonhuman primate embryo model, to compare
      expression between a primate and nonprimate species, and to determine whether
      disruption of this pathway may contribute to reduced developmental potential, we
      examined the expression of >50 mRNAs encoding UPP components in rhesus monkey
      oocytes and embryos. We compared this expression between the rhesus monkey and
      mouse embryo and between rhesus monkey oocytes and embryos of high, intermediate,
      and low developmental potential. We report here the temporal patterns of UPP gene
      expression in oocytes and during preimplantation development, including striking
      differences between the rhesus monkey and mouse. We also report significant
      differences in UPP gene expression correlating with oocyte and embryo
      developmental competence and associated with altered regulation of maternally
      inherited mRNAs encoding these proteins.

PMID- 17550998
TI  - Long-term testosterone supplementation augments overnight growth hormone
      secretion in healthy older men.
AB  - Circulating testosterone (T) and GH/IGF-I are diminished in healthy aging men.
      Short-term administration of high doses of T augments GH secretion in older men.
      However, effects of long-term, low-dose T supplementation on GH secretion are
      unknown. Our objective was to evaluate effects of long-term, low-dose T
      administration on nocturnal GH secretory dynamics and AM concentrations of IGF-I
      and IGFBP-3 in healthy older men (65-88 yr, n = 34) with low-normal T and IGF-I.
      In a double-masked, placebo-controlled, randomized study we assessed effects of
      low-dose T supplementation (100 mg im every 2 wk) for 26 wk on nocturnal GH
      secretory dynamics [8 PM to 8 AM, Q(20) min sampling, analyzed by multiparameter
      deconvolution and approximate entropy (ApEn) algorithms]. The results were that T
      administration increased serum total T by 33% (P = 0.004) and E(2) by 31% (P =
      0.009) and decreased SHBG by 17% (P = 0.002) vs. placebo. T supplementation
      increased nocturnal integrated GH concentrations by 60% (P = 0.02) and pulsatile
      GH secretion by 79% (P = 0.05), primarily due to a twofold increase in GH
      secretory burst mass (P = 0.02) and a 1.9-fold increase in basal GH secretion
      rate (P = 0.05) vs. placebo. There were no significant changes in GH burst
      frequency or orderliness of GH release (ApEn). IGF-I levels increased by 22% (P =
      0.02), with no significant change in IGFBP-3 levels after T vs. placebo. We
      conclude that low-dose T supplementation for 26 wk increases spontaneous
      nocturnal GH secretion and morning serum IGF-I concentrations in healthy older
      men.

PMID- 17550999
TI  - Two phases of palmitate-induced insulin resistance in skeletal muscle: impaired
      GLUT4 translocation is followed by a reduced GLUT4 intrinsic activity.
AB  - We examined, in soleus muscle, the effects of prolonged palmitate exposure (0, 6,
      12, 18 h) on insulin-stimulated glucose transport, intramuscular lipid
      accumulation and oxidation, activation of selected insulin-signaling proteins,
      and the insulin-stimulated translocation of GLUT4. Insulin-stimulated glucose
      transport was progressively reduced after 6 h (-33%), 12 h (-66%), and 18 h (
      89%) of palmitate exposure. These decrements were closely associated with
      concurrent reductions in palmitate oxidation at 6 h (-40%), 12 h (-60%), and 18 h
      (-67%). In contrast, intramuscular ceramide (+24%) and diacylglycerol (+32%)
      concentrations, insulin-stimulated AS160 (-36%) and PRAS40 (-33%)
      phosphorylations, and Akt (-40%), PKCtheta (-50%), and GLUT4 translocation (-40%)
      to the plasma membrane were all maximally altered within the first 6 h of
      palmitate treatment. No further changes were observed in any of these parameters
      after 12 and 18 h of palmitate exposure. Thus, the intrinsic activity of GLUT4
      was markedly reduced after 12 and 18 h of palmitate treatment. During this
      reduced GLUT4 intrinsic activity phase at 12 and 18 h, the reduction in glucose
      transport was twofold greater compared with the early phase (< or =6 h), when
      only GLUT4 translocation was impaired. Our study indicates that palmitate-induced
      insulin resistance is provoked by two distinct mechanisms: 1) an early phase (<
      or =6 h), during which lipid-mediated impairments in insulin signaling and GLUT4
      translocation reduce insulin-stimulated glucose transport, followed by 2) a later
      phase (12 and 18 h), during which the intrinsic activity of GLUT4 is markedly
      reduced independently of any further alterations in intramuscular lipid
      accumulation, insulin signaling and GLUT4 translocation.

PMID- 17551000
TI  - Acute effect of insulin on nitric oxide synthesis in humans: a precursor-product
      isotopic study.
AB  - Nitric oxide (NO) is a key regulatory molecule with wide vascular, cellular, and
      metabolic effects. Insulin affects NO synthesis in vitro. No data exist on the
      acute effect of insulin on NO kinetics in vivo. By employing a precursor-product
      tracer method in humans, we have directly estimated the acute effect of insulin
      on intravascular NO(x) (i.e., the NO oxidation products) fractional (FSR) and
      absolute (ASR) synthesis rates in vivo. Nine healthy male volunteers were infused
      iv with L-[(15)N(2)-guanidino]arginine ([(15)N(2)]arginine) for 6 h. Timed
      measurements of (15)NO(x) and [(15)N(2)]arginine enrichments in whole blood were
      performed in the first 3 h in the fasting state and then following a 3-h
      euglycemic-hyperinsulinemic clamp (with plasma insulin raised to approximately
      1,000 pmol/l). In the last 60 min of each experimental period, at approximately
      steady-state arginine enrichment, a linear increase of (15)NO(x) enrichment (mean
      r = 0.9) was detected in both experimental periods. In the fasting state, NO(x)
      FSR was 27.4 +/- 4.3%/day, whereas ASR was 0.97 +/- 0.36 mmol/day, accounting for
      0.69 +/- 0.27% of arginine flux. Following hyperinsulinemia, both FSR and ASR of
      NO(x) increased (FSR by approximately 50%, to 42.4 +/- 6.7%/day, P < 0.005; ASR
      by approximately 25%, to 1.22 +/- 0.41 mmol/day, P = 0.002), despite a
      approximately 20-30% decrease of arginine flux and concentration. The fraction of
      arginine flux used for NO(x) synthesis was doubled, to 1.13 +/- 0.35% (P <
      0.003). In conclusion, whole body NO(x) synthesis can be directly measured over a
      short observation time with stable isotope methods in humans. Insulin acutely
      stimulates NO(x) synthesis from arginine.

PMID- 17551001
TI  - LCAT-null mice develop improved hepatic insulin sensitivity through altered
      regulation of transcription factors and suppressors of cytokine signaling.
AB  - We previously reported that LCAT-deficient mice develop not only low HDL
      cholesterol but also hypertriglyceridemia, hepatic triglyceride (TG)
      overproduction, and, unexpectedly, improved hepatic insulin sensitivity and
      reduced hepatic TG content. Here, we examined the mechanistic links underlying
      this apparent paradox. The LDL receptor-deficient (Ldlr)(-/-)xLcat(-/-) mouse
      model and age- and sex-matched Ldlr(-/-)xLcat(+/+) littermates, both in C57Bl/6
      background, were employed. Studies of hepatic insulin signal transduction showed
      an upregulation of hepatic Irs2 mRNA level (5.3-fold, P = 0.02), IRS-2 protein
      mass level (1.5-fold, P = 0.009) and pIRS-2 (1.8-fold. P = 0.02) in the Ldlr(-/
      )xLcat(-/-) mice. There was a 1.2-fold increase in pAkt (P = 0.03) with a
      nonsignificant change in total Akt. We observed a significant shift in its
      downstream transcription factor FoxO-1 to the cytosolic compartment (2.3-fold
      increase in cytosolic/nuclear ratio, P = 0.04). We also observed a significant
      3.1-fold increase in nuclear abundance of FoxA-2 mass (P = 0.017) and a 1.5-fold
      upregulation of its coactivator PGC-1beta (P = 0.002), the coordinated actions of
      which promotes hepatic TG production and beta-oxidation. Increased hepatic
      insulin signaling in the Ldlr(-/-)xLcat(-/-) mice was associated with an
      upregulation of the Tcfe3 gene (1.7-fold, P = 0.024), a selective downregulation
      of the Socs-1 gene by 60% (P = 0.01), and no change in PTP-1B protein mass. These
      data suggest that LCAT deficiency induces complex alterations in hepatic signal
      transduction cascades, which explain, at least in part, the observed enhanced
      insulin signaling in association with hepatic TG overproduction and reduced
      hepatic TG content.

PMID- 17551002
TI  - Glucose stimulates protein synthesis in skeletal muscle of neonatal pigs through
      an AMPK- and mTOR-independent process.
AB  - Skeletal muscle protein synthesis is elevated in neonates in part due to an
      enhanced response to the rise in insulin and amino acids after eating. In vitro
      studies suggest that glucose plays a role in protein synthesis regulation. To
      determine whether glucose, independently of insulin and amino acids, is involved
      in the postprandial rise in skeletal muscle protein synthesis, pancreatic
      substrate clamps were performed in neonatal pigs. Insulin secretion was inhibited
      with somatostatin and insulin was infused to reproduce fasting or fed levels,
      while glucose and amino acids were clamped at fasting or fed levels. Fractional
      protein synthesis rates and translational control mechanisms were examined.
      Raising glucose alone increased protein synthesis in fast-twitch glycolytic
      muscles but not in other tissues. The response in muscle was associated with
      increased phosphorylation of protein kinase B (PKB) and enhanced formation of the
      active eIF4E.eIF4G complex but no change in phosphorylation of AMP-activated
      protein kinase (AMPK), tuberous sclerosis complex 2 (TSC2), mammalian target of
      rapamycin (mTOR), 4E-binding protein-1 (4E-BP1), ribosomal protein S6 kinase
      (S6K1), or eukaryotic elongation factor 2 (eEF2). Raising glucose, insulin, and
      amino acids increased protein synthesis in most tissues. The response in muscle
      was associated with phosphorylation of PKB, mTOR, S6K1, and 4E-BP1 and enhanced
      eIF4E.eIF4G formation. The results suggest that the postprandial rise in glucose,
      independently of insulin and amino acids, stimulates protein synthesis in
      neonates, and this response is specific to fast-twitch glycolytic muscle and
      occurs by AMPK- and mTOR-independent pathways.

PMID- 17551003
TI  - The effect of training on the expression of mitochondrial biogenesis- and
      apoptosis-related proteins in skeletal muscle of patients with mtDNA defects.
AB  - Mitochondrial myopathy patients (MMPs) have impaired oxidative phosphorylation
      and exercise intolerance. Endurance training of MMPs improves exercise tolerance,
      but also increases mutational load. To assess the regulation of mitochondrial
      content in MMPs, we measured proteins involved in 1) biogenesis, 2) oxidative
      stress, and 3) apoptosis in MMPs and healthy controls (HCs) both before and after
      endurance training. Before training, MMPs had a greater mitochondrial content,
      along with a 1.4-fold (P < 0.05) higher expression of the biogenesis regulator
      peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha).
      The DNA repair enzyme 8-oxoguanine DNA glycolase-1 (OGG-1), the antioxidant
      manganese superoxide dismutase (MnSOD), and the apoptotic proteins AIF and Bcl-2
      were higher in MMPs compared with HCs. Aconitase, an enzyme sensitive to
      oxidative stress, was 52% lower (P < 0.05) in MMPs when calculated based on an
      estimate of mitochondrial volume and oxidative stress-induced protein
      modifications tended to be higher in MMPs compared with HCs. Endurance training
      (ET) induced increases in mitochondrial content in both HC subjects and MMPs, but
      there was no effect of training on the regulatory proteins Tfam or PGC-1alpha. In
      MMPs, training induced a selective reduction of OGG-1, an increase in MnSOD, and
      a reduction in aconitase activity. Thus, before training, MMPs exhibited an
      adaptive response of nuclear proteins indicative of a compensatory increase in
      mitochondrial content. Following training, several parallel adaptations occurred
      in MMPs and HCs, which may contribute to previously observed functional
      improvements of exercise in MMPs. However, our results indicate that muscle from
      MMPs may be exposed to greater levels of oxidative stress during the course of
      training. Further investigation is required to evaluate the long-term benefits of
      endurance training as a therapeutic intervention for mitochondrial myopathy
      patients.

PMID- 17551004
TI  - Involvement of host cellular multivesicular body functions in hepatitis B virus
      budding.
AB  - Hepatitis B virus (HBV) is a major human pathogen that chronically infects
      approximately 350 million people, causing liver disease and liver cancer. HBV
      virions bud into an endoplasmic reticulum (ER)-associated intracellular
      compartment, but the mechanisms of HBV assembly, budding, and release remain
      poorly understood. Budding of retroviruses and some other enveloped RNA viruses
      from plasma membranes requires host functions involved in protein sorting into
      late endosomal multivesicular bodies (MVBs). To determine whether budding of DNA
      containing HBV virions at intracellular membranes also involves MVB functions, we
      used immunofluorescence to show that, in human hepatoma cells, HBV envelope
      protein colocalizes with MVB proteins AIP1/ALIX and VPS4B. We also found that a
      dominant negative (DN) AIP1 mutant inhibited production and/or release of
      enveloped virions without significant effects on intracellular nucleocapsid
      formation, whereas DN VPS4B inhibited both nucleocapsid production and budding.
      By contrast, DN AIP1 and VPS4 had no effect on the efficiency of release of
      enveloped, nucleocapsid-lacking HBV subviral particles, which are produced in
      vast excess over virions, and dramatically increased the release of unenveloped,
      naked nucleocapsids by an apparently nonlytic route. Thus, host MVB functions are
      required for efficient budding and release of enveloped HBV virions and may be a
      valuable target for HBV control. Moreover, HBV enveloped virions, enveloped
      subviral particles, and unenveloped nucleocapsids are all released by distinct
      pathways with separate host factor requirements.

PMID- 17551005
TI  - Evaluating a technological fix for climate.

PMID- 17551006
TI  - Systematic prediction and validation of breakpoints associated with copy-number
      variants in the human genome.
AB  - Copy-number variants (CNVs) are an abundant form of genetic variation in humans.
      However, approaches for determining exact CNV breakpoint sequences (physical
      deletion or duplication boundaries) across individuals, crucial for associating
      genotype to phenotype, have been lacking so far, and the vast majority of CNVs
      have been reported with approximate genomic coordinates only. Here, we report an
      approach, called BreakPtr, for fine-mapping CNVs (available from
      http://breakptr.gersteinlab.org). We statistically integrate both sequence
      characteristics and data from high-resolution comparative genome hybridization
      experiments in a discrete-valued, bivariate hidden Markov model. Incorporation of
      nucleotide-sequence information allows us to take into account the fact that
      recently duplicated sequences (e.g., segmental duplications) often coincide with
      breakpoints. In anticipation of an upcoming increase in CNV data, we developed an
      iterative, "active" approach to initially scoring with a preliminary model,
      performing targeted validations, retraining the model, and then rescoring, and a
      flexible parameterization system that intuitively collapses from a full model of
      2,503 parameters to a core one of only 10. Using our approach, we accurately
      mapped >400 breakpoints on chromosome 22 and a region of chromosome 11, refining
      the boundaries of many previously approximately mapped CNVs. Four predicted
      breakpoints flanked known disease-associated deletions. We validated an
      additional four predicted CNV breakpoints by sequencing. Overall, our results
      suggest a predictive resolution of approximately 300 bp. This level of resolution
      enables more precise correlations between CNVs and across individuals than
      previously possible, allowing the study of CNV population frequencies. Further,
      it enabled us to demonstrate a clear Mendelian pattern of inheritance for one of
      the CNVs.

PMID- 17551007
TI  - Imaging protein-protein interactions in plants and single cells.

PMID- 17551009
TI  - Robust coding of flow-field parameters by axo-axonal gap junctions between fly
      visual interneurons.
AB  - Complex flight maneuvers require a sophisticated system to exploit the optic flow
      resulting from moving images of the environment projected onto the retina. In the
      fly's visual course control center, the lobula plate, 10 so-called vertical
      system (VS) cells are thought to match, with their complex receptive fields, the
      optic flow resulting from rotation around different body axes. However, signals
      of single VS cells are unreliable indicators of such optic flow parameters in the
      context of their noisy, texture-dependent input from local motion measurements.
      Here we propose an alternative encoding scheme based on network simulations of
      biophysically realistic compartmental models of VS cells. The simulations
      incorporate recent data about the highly selective connectivity between VS cells
      consisting of an electrical axo-axonal coupling between adjacent cells and a
      reciprocal inhibition between the most distant cells. We find that this
      particular wiring performs a linear interpolation between the output signals of
      VS cells, leading to a robust representation of the axis of rotation even in the
      presence of textureless patches of the visual surround.

PMID- 17551008
TI  - Three-dimensional structure of a human connexin26 gap junction channel reveals a
      plug in the vestibule.
AB  - Connexin molecules form intercellular membrane channels facilitating electronic
      coupling and the passage of small molecules between adjoining cells. Connexin26
      (Cx26) is the second smallest member of the gap junction protein family, and
      mutations in Cx26 cause certain hereditary human diseases such as skin disorders
      and hearing loss. Here, we report the electron crystallographic structure of a
      human Cx26 mutant (M34A). Although crystallization trials used hemichannel
      preparations, the density map revealed that two hemichannels redocked at their
      extracellular surfaces into full intercellular channels. These orthorhombic
      crystals contained two sets of symmetry-related intercellular channels within
      three lipid bilayers. The 3D map shows a prominent density in the pore of each
      hemichannel. This density contacts the innermost helices of the surrounding
      connexin subunits at the bottom of the vestibule. The density map suggests that
      physical blocking may play an important role that underlies gap junction channel
      regulation. Our structure allows us to suggest that the two docked hemichannels
      can be independent and may regulate their activity autonomously with a plug in
      the vestibule.

PMID- 17551010
TI  - Structural and thermodynamic characterization of a cytoplasmic dynein light chain
      intermediate chain complex.
AB  - Cytoplasmic dynein is a microtubule-based motor protein complex that plays
      important roles in a wide range of fundamental cellular processes, including
      vesicular transport, mitosis, and cell migration. A single major form of
      cytoplasmic dynein associates with membranous organelles, mitotic kinetochores,
      the mitotic and migratory cell cortex, centrosomes, and mRNA complexes. The
      ability of cytoplasmic dynein to recognize such diverse forms of cargo is thought
      to be associated with its several accessory subunits, which reside at the base of
      the molecule. The dynein light chains (LCs) LC8 and TcTex1 form a subcomplex with
      dynein intermediate chains, and they also interact with numerous protein and
      ribonucleoprotein partners. This observation has led to the hypothesis that these
      subunits serve to tether cargo to the dynein motor. Here, we present the
      structure and a thermodynamic analysis of a complex of LC8 and TcTex1 associated
      with their intermediate chain scaffold. The intermediate chains effectively block
      the major putative cargo binding sites within the light chains. These data
      suggest that, in the dynein complex, the LCs do not bind cargo, in apparent
      disagreement with a role for LCs in dynein cargo binding interactions.

PMID- 17551011
TI  - Alternating electric fields arrest cell proliferation in animal tumor models and
      human brain tumors.
AB  - We have recently shown that low intensity, intermediate frequency, electric
      fields inhibit by an anti-microtubule mechanism of action, cancerous cell growth
      in vitro. Using implanted electrodes, these fields were also shown to inhibit the
      growth of dermal tumors in mice. The present study extends these findings to
      additional cell lines [human breast carcinoma; MDA-MB-231, and human non-small
      cell lung carcinoma (H1299)] and to animal tumor models (intradermal B16F1
      melanoma and intracranial F-98 glioma) using external insulated electrodes. These
      findings led to the initiation of a pilot clinical trial of the effects of
      TTFields in 10 patients with recurrent glioblastoma (GBM). Median time to disease
      progression in these patients was 26.1 weeks and median overall survival was 62.2
      weeks. These time to disease progression and OS values are more than double the
      reported medians of historical control patients. No device-related serious
      adverse events were seen after >70 months of cumulative treatment in all of the
      patients. The only device-related side effect seen was a mild to moderate contact
      dermatitis beneath the field delivering electrodes. We conclude that TTFields are
      a safe and effective new treatment modality which effectively slows down tumor
      growth in vitro, in vivo and, as demonstrated here, in human cancer patients.

PMID- 17551012
TI  - Six closely related YbT2Zn20 (T = Fe, Co, Ru, Rh, Os, Ir) heavy fermion compounds
      with large local moment degeneracy.
AB  - Heavy fermion compounds represent one of the most strongly correlated forms of
      electronic matter and give rise to low temperature states that range from small
      moment ordering to exotic superconductivity, both of which are often in close
      proximity to quantum critical points. These strong electronic correlations are
      associated with the transfer of entropy from the local moment degrees of freedom
      to the conduction electrons, and, as such, are intimately related to the low
      temperature degeneracy of the (originally) moment bearing ion. Here we report the
      discovery of six closely related Yb-based heavy fermion compounds, YbT(2)Zn(20),
      that are members of the larger family of dilute rare earth bearing compounds:
      RT(2)Zn(20) (T = Fe, Co, Ru, Rh, Os, Ir). This discovery doubles the total number
      of Yb-based heavy fermion materials. Given these compounds' dilute nature,
      systematic changes in T only weakly perturb the Yb site and allow for insight
      into the effects of degeneracy on the thermodynamic and transport properties of
      these model correlated electron systems.

PMID- 17551013
TI  - Imaging protein interactions with bioluminescence resonance energy transfer
      (BRET) in plant and mammalian cells and tissues.
AB  - FRET is a well established method for cellular and subcellular imaging of protein
      interactions. However, FRET obligatorily necessitates fluorescence excitation
      with its concomitant problems of photobleaching, autofluorescence, phototoxicity,
      and undesirable stimulation of photobiological processes. A sister technique,
      bioluminescence resonance energy transfer (BRET), avoids these problems because
      it uses enzyme-catalyzed luminescence; however, BRET signals usually have been
      too dim to image effectively in the past. Using a new generation electron
      bombardment-charge-coupled device camera coupled to an image splitter, we
      demonstrate that BRET can be used to image protein interactions in plant and
      animal cells and in tissues; even subcellular imaging is possible. We have
      applied this technology to image two different protein interactions: (i)
      dimerization of the developmental regulator, COP1, in plant seedlings; and (ii)
      CCAAT/enhancer binding protein alpha (C/EBPalpha) in the mammalian nucleus. This
      advance heralds a host of applications for imaging without fluorescent excitation
      and its consequent limitations.

PMID- 17551014
TI  - Synthetic ecosystems based on airborne inter- and intrakingdom communication.
AB  - Intercellular communication within an organism, between populations, or across
      species and kingdoms forms the basis of many ecosystems in which organisms
      coexist through symbiotic, parasitic, or predator-prey relationships. Using
      multistep airborne communication and signal transduction, we present synthetic
      ecosystems within a mammalian cell population, in mice, or across species and
      kingdoms. Inter- and intrakingdom communication was enabled by using sender cells
      that produce volatile aldehydes, small vitamin-derived molecules, or antibiotics
      that diffuse, by gas or liquid phase, to receiver cells and induce the expression
      of specific target genes. Intercellular and cross-kingdom communication was shown
      to enable quorum sensing between and among mammalian cells, bacteria, yeast, and
      plants, resulting in precise spatiotemporal control of IFN-beta production.
      Interconnection of bacterial, yeast, and mammalian cell signaling enabled the
      construction of multistep signal transduction and processing networks as well as
      the design of synthetic ecosystems that mimic fundamental coexistence patterns in
      nature, including symbiosis, parasitism, and oscillating predator-prey
      interactions.

PMID- 17551015
TI  - Transient 2D IR spectroscopy of ubiquitin unfolding dynamics.
AB  - Transient two-dimensional infrared (2D IR) spectroscopy is used as a probe of
      protein unfolding dynamics in a direct comparison of fast unfolding experiments
      with molecular dynamics simulations. In the experiments, the unfolding of
      ubiquitin is initiated by a laser temperature jump, and protein structural
      evolution from nanoseconds to milliseconds is probed using amide I 2D IR
      spectroscopy. The temperature jump prepares a subensemble near the unfolding
      transition state, leading to quasi-barrierless unfolding (the "burst phase")
      before the millisecond activated unfolding kinetics. The burst phase unfolding of
      ubiquitin is characterized by a loss of the coupling between vibrations of the
      beta-sheet, a process that manifests itself in the 2D IR spectrum as a frequency
      blue-shift and intensity decrease of the diagonal and cross-peaks of the sheet's
      two IR active modes. As the sheet unfolds, increased fluctuations and solvent
      exposure of the beta-sheet amide groups are also characterized by increases in
      homogeneous linewidth. Experimental spectra are compared with 2D IR spectra
      calculated from the time-evolving structures in a molecular dynamics simulation
      of ubiquitin unfolding. Unfolding is described as a sequential unfolding of
      strands in ubiquitin's beta-sheet, using two collective coordinates of the sheet:
      (i) the native interstrand contacts between adjacent beta-strands I and II and
      (ii) the remaining beta-strand contacts within the sheet. The methods used
      illustrate the general principles by which 2D IR spectroscopy can be used for
      detailed dynamical comparisons of experiment and simulation.

PMID- 17551016
TI  - Differential homing mechanisms regulate regionalized effector CD8alphabeta+ T
      cell accumulation within the small intestine.
AB  - The CC chemokine receptor (CCR)9 is expressed on the majority of small
      intestinal, but few colonic, T cells, whereas its ligand CCL25 is constitutively
      expressed by small intestinal epithelial cells. As such, CCR9/CCL25 have been
      proposed to play a central role in regulating small intestinal but not colonic
      immune responses and thus to organize regionalized immunity within the intestinal
      mucosa. Here, we demonstrate that CCL25 is expressed at reduced levels by
      epithelial cells in the distal compared with proximal small intestine, which
      correlated with less efficient CCR9-dependent effector CD8alphabeta+ T cell entry
      into the ileal epithelium. In vitro-generated alpha4beta7+ effector CD8alphabeta+
      T cell entry into the lamina propria was less dependent on CCR9 than entry into
      the epithelium along the entire length of the small intestine and in particular
      in the ileum. CCR9-independent alpha4beta7+ effector CD8alphabeta+ T cell entry
      was pertussis toxin-sensitive, suggesting a role for additional Galpha(I)-linked
      G protein-coupled receptors. Finally, in vivo-primed effector CD8alphabeta+ T
      cells displayed regionalized differences in their entry to the small intestinal
      epithelium with enhanced CCR9-independent entry to the ileum. These results
      highlight a hitherto underappreciated compartmentalization of immune responses
      within the small intestine and have direct implications for targeting strategies
      aimed at regulating T cell localization to the small intestinal mucosa.

PMID- 17551017
TI  - Ventrolateral prefrontal cortex and tactile memory disambiguation in the human
      brain.
AB  - Tactile sensory information is first channeled from the primary somatosensory
      cortex on the postcentral gyrus to the parietal opercular region (i.e., the
      secondary somatosensory cortex) and the rostral inferior parietal lobule and,
      from there, to the prefrontal cortex, with which bidirectional connections exist.
      Although we know that tactile memory signals can be found in the prefrontal
      cortex, the contribution of the different prefrontal areas to tactile memory
      remains unclear. The present functional MRI study shows that a specific part of
      the prefrontal cortex in the human brain, namely the midventrolateral prefrontal
      region (cytoarchitectonic areas 47/12 and 45), is involved in active controlled
      retrieval processing necessary for the disambiguation of vibrotactile information
      in short-term memory. Furthermore, we demonstrate that this particular part of
      the prefrontal cortex interacts functionally with the secondary somatosensory
      areas in the parietal operculum and the rostral inferior parietal lobule during
      controlled processing for the retrieval of specific tactile information.

PMID- 17551018
TI  - Acute stress increases interstitial fluid amyloid-beta via corticotropin
      releasing factor and neuronal activity.
AB  - Aggregation of the amyloid-beta (Abeta) peptide in the extracellular space of the
      brain is critical in the pathogenesis of Alzheimer's disease. Abeta is produced
      by neurons and released into the brain interstitial fluid (ISF), a process
      regulated by synaptic activity. To determine whether behavioral stressors can
      regulate ISF Abeta levels, we assessed the effects of chronic and acute stress
      paradigms in amyloid precursor protein transgenic mice. Isolation stress over 3
      months increased Abeta levels by 84%. Similarly, acute restraint stress increased
      Abeta levels over hours. Exogenous corticotropin-releasing factor (CRF) but not
      corticosterone mimicked the effects of acute restraint stress. Inhibition of
      endogenous CRF receptors or neuronal activity blocked the effects of acute stress
      on Abeta. Thus, behavioral stressors can rapidly increase ISF Abeta through
      neuronal activity in a CRF-dependent manner, and the results suggest a mechanism
      by which behavioral stress may affect Alzheimer's disease pathogenesis.

PMID- 17551019
TI  - Rapid bulk endocytosis and its kinetics of fission pore closure at a central
      synapse.
AB  - Upon exocytosis, fused vesicles must be retrieved for recycling. One route of
      retrieval is to generate endosome-like structures, from which small vesicles bud
      off. Endosome-like structures are widely thought to be generated slowly (
      approximately 1 min) from the plasma membrane, a process called bulk endocytosis.
      Although the concept of bulk endocytosis seems established, the kinetic evidence
      showing the instant of the bulk membrane fission at synapses is still missing.
      The present work provides this missing piece of evidence at a calyx-type synapse.
      We used the capacitance measurement technique, which offers a high time
      resolution ( approximately 1 ms) to resolve the fission process. The instant of
      bulk membrane fission was reflected as a brief downward capacitance shift (DCS)
      of approximately 20-500 fF (mean = 123 fF) with 10-90% decay time of
      approximately 30-500 ms. At least 8.6-11.0% of exocytosed vesicles were retrieved
      by DCSs. During a DCS, the decrease in the fission pore conductance was detected,
      from which we found that the fission pore diameter decreased at approximately 39
      nm/s. This provided the measurement of the rate of fission during bulk
      endocytosis at synapses. The DCS frequency peaked (approximately equal to 0.021
      Hz) in <10 s after stimulation and decayed with a half time <20 s, indicating
      that the time course of bulk endocytosis is much faster than previously estimated
      with low time-resolution techniques. Our results also suggest that bulk
      endocytosis was composed of two kinetically different steps: the DCS that
      reflected the fission process and the time between stimulation and the DCS,
      during which membrane invagination led to the fission pore formation.

PMID- 17551020
TI  - Inhibition of spinal microglial cathepsin S for the reversal of neuropathic pain.
AB  - A recent major conceptual advance has been the recognition of the importance of
      immune system-neuronal interactions in the modulation of brain function, one
      example of which is spinal pain processing in neuropathic states. Here, we report
      that in peripheral nerve-injured rats, the lysosomal cysteine protease cathepsin
      S (CatS) is critical for the maintenance of neuropathic pain and spinal microglia
      activation. After injury, CatS was exclusively expressed by activated microglia
      in the ipsilateral dorsal horn, where expression peaked at day 7, remaining high
      on day 14. Intrathecal delivery of an irreversible CatS inhibitor, morpholinurea
      leucine-homophenylalanine-vinyl phenyl sulfone (LHVS), was antihyperalgesic and
      antiallodynic in neuropathic rats and attenuated spinal microglia activation.
      Consistent with a pronociceptive role of endogenous CatS, spinal intrathecal
      delivery of rat recombinant CatS (rrCatS) induced hyperalgesia and allodynia in
      naive rats and activated p38 mitogen-activated protein kinase (MAPK) in spinal
      cord microglia. A bioinformatics approach revealed that the transmembrane
      chemokine fractalkine (FKN) is a potential substrate for CatS cleavage. We show
      that rrCatS incubation reduced the levels of cell-associated FKN in cultured
      sensory neurons and that a neutralizing antibody against FKN prevented both FKN-
      and CatS-induced allodynia, hyperalgesia, and p38 MAPK activation. Furthermore,
      rrCatS induced allodynia in wild-type but not CX3CR1-knockout mice. We suggest
      that under conditions of increased nociception, microglial CatS is responsible
      for the liberation of neuronal FKN, which stimulates p38 MAPK phosphorylation in
      microglia, thereby activating neurons via the release of pronociceptive
      mediators.

PMID- 17551021
TI  - Evolution of robustness in the signaling network of Pristionchus vulva
      development.
AB  - Robustness to environmental or genetic perturbation, like any other trait, is
      affected by evolutionary change. However, direct studies on the interplay of
      robustness and evolvability are limited and require experimental
      microevolutionary studies of developmental processes. One system in which such
      microevolutionary studies can be performed is vulva development in the nematode
      Pristionchus pacificus. Three vulval precursor cells respond to redundant cell
      cell interactions, including signals from the gonad and the epidermal cell P8.p.
      Interestingly, P. pacificus P8.p is involved in cell fate specification of the
      future vulva cells by lateral inhibition but is incompetent to respond to the
      inductive signal from the gonad itself. These functional properties of P8.p are
      unknown from other nematodes, such as Caenorhabditis elegans. We began an
      experimental and genetic analysis of the microevolution of P8.p function. We show
      that vulva misspecification events differ between Pristionchus strains and
      species. Similarly, lateral inhibition and developmental competence of P8.p
      evolved within the genus Pristionchus and between natural isolates of P.
      pacificus. Surprisingly, in some recombinant inbred lines of two distinct P.
      pacificus isolates, P8.p gained competence to form vulva tissue, a trait that was
      never observed in P. pacificus isolates. Our results suggest differences in
      developmental stability between natural isolates, and we hypothesize that the
      remarkable evolvability of redundant cell-cell interactions allows for adaptive
      evolution of robustness to developmental noise.

PMID- 17551024
TI  - On the identification of some Entamoeba species - response to Ponce-Gordo and
      Martinez-Diaz.

PMID- 17551025
TI  - Frondicola australicus gen. nov., sp. nov., isolated from decaying leaf litter
      from a pine forest.
AB  - An aerobic bacterium, designated strain E1HC-02(T), was isolated from the
      decaying leaf litter of a slash pine forest located in southeast Queensland,
      Australia. Cells of strain E1HC-02(T) were short irregular rods (0.5-1.0 x 0.2
      0.4 microm) which stained Gram-positive and possessed a cell-wall ultrastructure
      which appeared to be made of protein subunits. The novel strain grew optimally in
      1 % trypticase soy broth (TSB) at 25 degrees C and at a pH of 9.1. Strain E1HC
      02(T) metabolized a range of carbohydrates, organic acids and amino acids. The
      G+C content of the DNA was 71+/-1 mol% as determined by the thermal denaturation
      method. 16S rRNA gene sequence analysis of strain E1HC-02(T) showed that it was a
      member of the family Microbacteriaceae, phylum Actinobacteria. The cell wall
      contained a type B2beta peptidoglycan, the dominant cellular fatty acid was 18 :
      1omega7c and the major hydroxy fatty acid was 2-OH 14 : 0. The major menaquinones
      were MK-8 (76 %) and MK-7 (24 %) and the glycolipids present were
      disphosphatidylglycerol, phosphatidylglycerol and three unidentified
      phospholipids. The chemotaxonomic properties of strain E1HC-02(T) were distinctly
      different to all of the 17 genera of the family Microbacteriaceae and hence
      strain E1HC-02(T) is designated as representing a novel species of a new genus,
      Frondicola australicus gen. nov., sp. nov. The type strain of the type species is
      E1HC-02(T) (=JCM 13598(T)=DSM 17894(T)).

PMID- 17551026
TI  - Nocardia acidivorans sp. nov., isolated from soil of the island of Stromboli.
AB  - A Gram-positive, non-spore-forming bacterium (strain GW4-1778(T)) was isolated
      from soil of the Italian island of Stromboli. 16S rRNA gene sequence similarity
      studies showed that strain GW4-1778(T) is a member of the genus Nocardia, most
      closely related to Nocardia pseudobrasiliensis (GenBank accession no. DQ659914;
      98.6 %), Nocardia nova (Z36930; 98.6 %), Nocardia niigatensis (AB092563; 98.4 %),
      Nocardia jiangxiensis (AY639902; 98.0 %), Nocardia uniformis (Z46752; 98.0 %) and
      Nocardia miyunensis (AY639901; 97.8 %). Strain GW4-1778(T) could be distinguished
      from any other established Nocardia species by sequence similarity values of less
      than 97.5 %. Strain GW4-1778(T) exhibited a quinone system with the predominant
      compound MK-8 (H(4), omega-cycl) (99.5 %) and traces of MK-8 (H(4)),
      characteristic for the genus Nocardia. The polar lipid profile of strain GW4
      1778(T) consisted of the predominant compound diphosphatidylglycerol, moderate
      amounts of phosphatidylethanolamine, phosphatidylinositol, two
      phosphatidylinositol mannosides, a unknown polar lipid and trace amounts of two
      unknown lipids and the major fatty acids were C(15 : 0), C(16 : 0), C(17 :
      1)omega8c and 10-methyl C(17 : 0). The results of DNA-DNA hybridizations and
      physiological and biochemical tests allowed genotypic and phenotypic
      differentiation of strain GW4-1778(T) from related species with 16S rRNA gene
      similarities of >97.5 %. Therefore, strain GW4-1778(T) merits species status, for
      which the name Nocardia acidivorans sp. nov. is proposed, with the type strain
      GW4-1778(T) (=CCUG 53410(T)=CIP 109315(T)=DSM 45049(T)).

PMID- 17551027
TI  - Pigmentiphaga daeguensis sp. nov., isolated from wastewater of a dye works, and
      emended description of the genus Pigmentiphaga.
AB  - A Gram-negative, non-spore-forming, rod-shaped Pigmentiphaga-like bacterial
      strain, K110(T), was isolated from wastewater collected from a dye works in Korea
      and was subjected to a polyphasic taxonomic analysis. Strain K110(T) grew
      optimally at pH 7.0--8.0 and 37 degrees C in the presence of 0.5 % (w/v) NaCl. It
      contained Q-8 as the predominant ubiquinone and C(16 : 0), cyclo C(17 : 0) and
      cyclo C(19 : 0)omega8c as the major fatty acids. The major polar lipids were
      phosphatidylglycerol, phosphatidylethanolamine and two unidentified aminolipids.
      The DNA G+C content was 67.4 mol%. In a neighbour-joining phylogenetic tree
      constructed on the basis of 16S rRNA gene sequences, strain K110(T) joined
      Pigmentiphaga kullae, the sole species of the genus, at a bootstrap confidence
      level of 100 %. Strain K110(T) exhibited a 16S rRNA gene sequence similarity of
      99.4 % with respect to the type strain of P. kullae. Although strain K110(T) was
      found to be similar to P. kullae in terms of phenotypic properties, it differed
      in terms of motility, polar lipids, DNA-DNA relatedness and repetitive extragenic
      palindromic PCR genomic fingerprinting patterns. On the basis of phenotypic,
      phylogenetic and genetic data, strain K110(T) represents a novel species of the
      genus Pigmentiphaga, for which the name Pigmentiphaga daeguensis sp. nov. is
      proposed. The type strain is K110(T) (=KCTC 12838(T)=JCM 14330(T)).

PMID- 17551028
TI  - Mesorhizobium albiziae sp. nov., a novel bacterium that nodulates Albizia kalkora
      in a subtropical region of China.
AB  - A novel Mesorhizobium group associated with Albizia kalkora [Wang et al. (2006),
      Syst Appl Microbiol 29, 502-517] was further characterized. The seven strains in
      this group showed similar protein patterns and were different from defined
      Mesorhizobium species in SDS-PAGE of whole-cell proteins. The representative
      strain CCBAU 61158(T) formed a novel Mesorhizobium lineage in phylogenetic
      analyses of 16S rRNA, atpD, glnII and nifH genes. However, its nodC gene sequence
      was more similar to that of Rhizobium gallicum R602sp(T) than to those of
      Mesorhizobium species. DNA-DNA relatedness between CCBAU 61158(T) and reference
      strains of defined Mesorhizobium species was lower than 34.1 %. These results
      indicated that this Mesorhizobium group was a unique genomic species. The
      subtropical distribution, host origin, PCR-RFLP patterns of 16S rRNA genes, fatty
      acid profile and a series of phenotypic characteristics could be used as
      distinctive features of this group. This group is therefore proposed as a novel
      species, Mesorhizobium albiziae sp. nov., with CCBAU 61158(T) (=LMG 23507(T)=USDA
      4964(T)) as the type strain. Strain CCBAU 61158(T) could form effective nodules
      on Albizia julibrissin, Glycine max, Leucaena leucocephala and Phaseolus
      vulgaris.

PMID- 17551029
TI  - Corynebacterium ureicelerivorans sp. nov., a lipophilic bacterium isolated from
      blood culture.
AB  - A lipophilic coryneform bacterium isolated from a blood culture from a patient
      with signs of septicaemia was characterized by means of phenotypic and molecular
      taxonomic methods. Chemotaxonomic investigations revealed the presence of cell
      wall chemotype IV and short-chain mycolic acids, which are consistent with the
      genus Corynebacterium. The isolate was characterized biochemically by the very
      rapid (approx. 60 s) positive result that was obtained in a urease test in the
      API Coryne system. Comparative 16S rRNA gene sequencing demonstrated that the
      isolate belonged phylogenetically to the genus Corynebacterium. The values for
      sequence divergence (> or =1.4 %) with respect to known Corynebacterium species,
      together with phenotypic differences, show that the unidentified bacterium
      represents a novel member of this genus. On the basis of both the phenotypic and
      phylogenetic data, this isolate should be classified within a novel species of
      the genus Corynebacterium, for which the name Corynebacterium ureicelerivorans
      sp. nov. is proposed. The type strain is IMMIB RIV-2301(T) (=DSM 45051(T)=CCUG
      53377(T)).

PMID- 17551030
TI  - Leeia oryzae gen. nov., sp. nov., isolated from a rice field in Korea.
AB  - A strictly aerobic, non-spore-forming, Gram-negative bacterium, designated strain
      HW7(T), was isolated from a rice field in Korea. Cells of strain HW7(T) were
      short rod-shaped and motile with single polar flagella. The major cellular fatty
      acids of strain HW7(T) were C(16 : 0) and summed feature 3 (C(16 : 1)omega7c
      and/or iso-C(15 : 0) 2-OH). The genomic DNA G+C content was 56 mol% and the major
      isoprenoid quinone was Q-8. Phylogenetic analysis based on 16S rRNA gene
      sequences showed that strain HW7(T) forms a distinct lineage with respect to
      closely related genera within the class Betaproteobacteria and that the levels of
      16S rRNA gene sequence similarity with respect to the type species of related
      genera are less than 93 %. On the basis of the physiological and phylogenetic
      data, strain HW7(T) represents a novel genus and species of the
      Betaproteobacteria, for which the name Leeia oryzae gen. nov., sp. nov. is
      proposed. The type strain is HW7(T) (=KCTC 12585(T)=DSM 17879(T)).

PMID- 17551031
TI  - Alteromonas tagae sp. nov. and Alteromonas simiduii sp. nov., mercury-resistant
      bacteria isolated from a Taiwanese estuary.
AB  - Two mercury-resistant strains of heterotrophic, aerobic, marine bacteria,
      designated AT1(T) and AS1(T), were isolated from water samples collected from the
      Er-Jen River estuary, Tainan, Taiwan. Cells were Gram-negative rods that were
      motile by means of a single polar flagellum. Buds and prosthecae were produced.
      The two isolates required NaCl for growth and grew optimally at about 30 degrees
      C, 2-4 % NaCl and pH 7-8. They grew aerobically and were incapable of anaerobic
      growth by fermenting glucose or other carbohydrates. They grew and expressed
      Hg(2+)-reducing activity in liquid media containing HgCl(2). Strain AS1(T)
      reduced nitrate to nitrite. The predominant isoprenoid quinone was Q(8) (91.3
      99.9 %). The polar lipids of strain AT1(T) consisted of phosphatidylethanolamine
      (46.6 %), phosphatidylglycerol (28.9 %) and sulfolipid (24.5 %), whereas those of
      AS1(T) comprised phosphatidylethanolamine (48.2 %) and phosphatidylglycerol (51.8
      %). The two isolates contained C(16 : 1)omega7c and/or iso-C(15 : 0) 2-OH (22.4
      33.7 %), C(16 : 0) (19.0-22.7 %) and C(18 : 1)omega7c (11.3-11.7 %) as the major
      fatty acids. Strains AT1(T) and AS1(T) had DNA G+C contents of 43.1 and 45.3
      mol%, respectively. Phylogeny based on 16S rRNA gene sequences, together with
      data from morphological, physiological and chemotaxonomic characterization,
      indicated that the two isolates could be classified as representatives of two
      novel species in the genus Alteromonas, for which the names Alteromonas tagae sp.
      nov. (type strain AT1(T)=BCRC 17571(T)=JCM 13895(T)) and Alteromonas simiduii sp.
      nov. (type strain AS1(T)=BCRC 17572(T)=JCM 13896(T)) are proposed.

PMID- 17551032
TI  - Caenispirillum bisanense gen. nov., sp. nov., isolated from sludge of a dye
      works.
AB  - Two Gram-negative, non-spore-forming, motile and helical-shaped bacterial
      strains, K92(T) and K93, were isolated from sludge from a dye works in Korea, and
      their taxonomic positions were investigated by means of a polyphasic approach.
      Strains K92(T) and K93 grew optimally at 37 degrees C and pH 7.0-8.0 in the
      presence of 0.5 % (w/v) NaCl. They contained Q-10 as the predominant ubiquinone
      and C(18 : 1)omega7c as the major fatty acid. The major polar lipids were
      phosphatidylcholine, phosphatidylglycerol, diphosphatidylglycerol,
      phosphatidylethanolamine and two unidentified amino-group-containing lipids that
      were ninhydrin-positive. Their DNA G+C contents were 70.0 mol%. The 16S rRNA gene
      sequences of K92(T) and K93 showed no differences, and the two strains had a mean
      DNA-DNA relatedness of 93 %. Phylogenetic analyses based on 16S rRNA gene
      sequences showed that strains K92(T) and K93 formed a distinct evolutionary
      lineage within the Alphaproteobacteria. The 16S rRNA gene sequences of strains
      K92(T) and K93 exhibited similarity values of less than 91.5 % with respect to
      the 16S rRNA gene sequences of other members of the Alphaproteobacteria. The two
      strains were distinguishable from phylogenetically related genera through
      differences in several phenotypic properties. On the basis of the phenotypic,
      phylogenetic and genetic data, strains K92(T) and K93 represent a novel genus and
      species, for which the name Caenispirillum bisanense gen. nov., sp. nov. is
      proposed. The type strain of Caenispirillum bisanense is K92(T) (=KCTC
      12839(T)=JCM 14346(T)).

PMID- 17551033
TI  - Halomonas shengliensis sp. nov., a moderately halophilic, denitrifying, crude-oil
      utilizing bacterium.
AB  - A moderately halophilic bacterium, designated strain SL014B-85(T), was isolated
      from a crude-oil-contaminated saline soil from Shengli oilfield, Shandong
      Province, China. Cells were Gram-negative, aerobic, short rods with lateral
      flagella. Growth occurred at NaCl concentrations of 0-15 % (optimum 5-15 %), at
      10-42 degrees C (optimum 30 degrees C) and at pH 8.0-9.0 (optimum pH 8.5). The
      only respiratory quinone was Q9, and the main cellular fatty acids were C(18 :
      1)omega7c, C(16 : 0) and C(19 : 0) cyclo omega8c. The G+C content of the DNA was
      66.6 mol%. Phylogenetic analysis based on 16S rRNA gene sequences indicated that
      strain SL014B-85(T) belonged to the genus Halomonas in the Gammaproteobacteria,
      with highest sequence similarity of 98.1 and 97.8 % to Halomonas alimentaria DSM
      15356(T) and Halomonas ventosae DSM 15911(T), respectively. DNA-DNA relatedness
      values were below 40 % with members of closely related Halomonas species. Results
      of phenotypic, biochemical and phylogenetic analyses revealed that strain SL014B
      85(T) could be classified as representing a novel species of the genus Halomonas,
      for which the name Halomonas shengliensis sp. nov. is proposed. The type strain
      is SL014B-85(T) (=CGMCC 1.6444(T)=LMG 23897(T)).

PMID- 17551034
TI  - Dyadobacter koreensis sp. nov., isolated from fresh water.
AB  - A non-motile, rod-shaped, light-yellow-pigmented bacterium, designated strain
      WPCB159(T), was isolated from freshwater samples collected from the Woopo wetland
      in Korea. The cells were Gram-negative, aerobic and catalase- and oxidase
      positive. The major fatty acids were C(16 : 1)omega7c (34.8 %), iso-C(15 : 0)
      (24.2 %) and C(16 : 0) (9.4 %). The DNA G+C content was 44 mol%. A phylogenetic
      tree based on 16S rRNA gene sequences showed that strain WPCB159(T) forms a
      lineage within the genus Dyadobacter (family 'Flexibacteraceae') and is closely
      related to Dyadobacter hamtensis HHS 11(T) (97.8 % sequence similarity) and to
      other members of the genus Dyadobacter (95.2-96.8 % sequence similarity). The
      phenotypic characteristics and DNA-DNA hybridization relatedness data indicate
      that strain WPCB159(T) should be distinguished from D. hamtensis HHS 11(T). On
      the basis of the evidence presented in this study, strain WPCB159(T) represents a
      novel species of the genus Dyadobacter, for which the name Dyadobacter koreensis
      sp. nov. is proposed. The type strain is WPCB159(T) (=KCTC 12537(T)=NBRC
      101116(T)).

PMID- 17551035
TI  - Use of the novel phylogenetic marker dnaJ and DNA-DNA hybridization to clarify
      interrelationships within the genus Aeromonas.
AB  - The interrelationships of 27 Aeromonas strains were investigated using dnaJ
      sequences and DNA-DNA hybridization. dnaJ sequence similarities showed a stronger
      relationship with DNA-DNA relatedness values than did 16S rRNA gene sequence
      similarities. Additionally, dnaJ sequence analysis, with interspecies divergence
      over 5.2 % in most cases, gave better resolution than 16S rRNA gene sequences for
      the differentiation of strains at the species level. Relationships among
      Aeromonas species were therefore elucidated on the basis of dnaJ sequences and
      DNA-DNA reassociation. Strains of Aeromonas encheleia and Aeromonas sp. HG11 were
      unquestionably grouped in the same genetic species, since they shared 98.7 % dnaJ
      sequence similarity and 82-85 % genomic relatedness. The phylogenetically close
      relationships obtained from dnaJ sequence analysis (1.7-3.3 % genetic distance)
      were corroborated by high DNA-DNA relatedness (73-97 %) to support the previous
      suggestion that Aeromonas culicicola and Aeromonas allosaccharophila are later
      heterotypic synonyms of Aeromonas veronii. Our findings will contribute to the
      clarification of controversial relationships in the genus Aeromonas and also
      demonstrate that analysis of dnaJ sequences can be a powerful tool for
      interspecies study of the genus.

PMID- 17551036
TI  - Chromohalobacter salarius sp. nov., a moderately halophilic bacterium isolated
      from a solar saltern in Cabo de Gata, Almeria, southern Spain.
AB  - A moderately halophilic, Gram-negative bacterium (strain CG4.1(T)), which was
      isolated from a solar saltern at Cabo de Gata, a wildlife reserve located in the
      province of Almeria, southern Spain, was subjected to a polyphasic taxonomic
      study. This organism was an aerobic, motile rod that produced colonies with a
      yellow pigment. Strain CG4.1(T) grew at salinities of 3-25 % (w/v), at 15-45
      degrees C and at pH 5-9. The organism reduced nitrate, hydrolysed starch and had
      phenylalanine deaminase activity. The major fatty acids were C(18 : 1)omega7c,
      C(16 : 0) and C(19 : 0) cyclo omega8c. The DNA G+C content was 63.6 mol%. On the
      basis of phenotypic and phylogenetic data, strain CG4.1(T) appears to be a member
      of the genus Chromohalobacter and clustered closely with Chromohalobacter
      species, with 95-96 % similarity between their 16S rRNA gene sequences. However,
      DNA-DNA relatedness between the isolate and the type strains of Chromohalobacter
      species was low. Therefore, it is proposed that strain CG4.1(T) represents a
      novel species, Chromohalobacter salarius sp. nov. The type strain is strain
      CG4.1(T) (=CECT 5903(T)=LMG 23626(T)).

PMID- 17551037
TI  - Halobacillus profundi sp. nov. and Halobacillus kuroshimensis sp. nov.,
      moderately halophilic bacteria isolated from a deep-sea methane cold seep.
AB  - Two Gram-positive, rod-shaped, moderately halophilic bacteria were isolated from
      a deep-sea carbonate rock at a methane cold seep in Kuroshima Knoll, Japan. These
      bacteria, strains IS-Hb4(T) and IS-Hb7(T), were spore-forming and non-motile.
      They were able to grow at temperatures as low as 9 degrees C and hydrostatic
      pressures up to 30 MPa. Based on high sequence similarity of their 16S rRNA genes
      to those of type strains of the genus Halobacillus, from 96.4 % (strain IS-Hb7(T)
      to Halobacillus halophilus NCIMB 9251(T)) to 99.4 % (strain IS-Hb4(T) to
      Halobacillus dabanensis D-8(T)), the strains were shown to belong to this genus.
      DNA-DNA relatedness values of 49.5 % and 1.0-33.0 %, respectively, were
      determined between strains IS-Hb4(T) and IS-Hb7(T) and between these strains and
      other Halobacillus type strains. Both strains showed the major menaquinone MK7
      and L-orn-D-Asp cell-wall peptidoglycan type. Straight-chain C(16 : 0),
      unsaturated C(16 : 1)omega7c alcohol and C(18 : 1)omega7c and cyclopropane C(19 :
      0) cyc fatty acids were predominant in both strains. The DNA G+C contents of IS
      Hb4(T) and IS-Hb7(T) were respectively 43.3 and 42.1 mol%. Physiological and
      biochemical analyses combined with DNA-DNA hybridization results allowed us to
      place strains IS-Hb4(T) (=JCM 14154(T)=DSM 18394(T)) and IS-Hb7(T) (=JCM
      14155(T)=DSM 18393(T)) in the genus Halobacillus as the respective type strains
      of the novel species Halobacillus profundi sp. nov. and Halobacillus
      kuroshimensis sp. nov.

PMID- 17551038
TI  - Rhodobium pfennigii sp. nov., a phototrophic purple non-sulfur bacterium with
      unusual bacteriochlorophyll a antennae, isolated from a brackish microbial mat on
      Rangiroa atoll, French Polynesia.
AB  - A novel budding purple non-sulfur bacterium (strain AR2102(T)) was isolated in
      pure culture from a microbial mat that had developed in brackish-water ponds on
      the coral rim of the atoll of Rangiroa (Tuamotu Islands, French Polynesia).
      Single cells of this strain were rod-shaped and motile by means of polar flagella
      and divided by budding. Their intracellular photosynthetic membranes were of the
      lamellar type. Bacteriochlorophyll a and carotenoids of the normal
      spirilloxanthin series, with spirilloxanthin as the main carotenoid, were present
      as photosynthetic pigments. Bacteriochlorophyll a absorption in the infrared
      portion of the light spectrum exhibited an unusual in vivo absorption peak at 909
      nm. The strain grew optimally under photoheterotrophic conditions, but could grow
      photolithotrophically on thiosulfate or chemo-organotrophically under micro-oxic
      conditions. Optimal growth occurred in the presence of 1-2 % NaCl. Comparative
      sequence analysis of the 16S rRNA gene placed strain AR2102(T) within the class
      Alphaproteobacteria, in a cluster with Rhodobium species. Representatives of this
      cluster form a closely related group of slightly to moderately halotolerant to
      halophilic, rod-shaped, purple non-sulfur bacteria that divide by budding. The
      new isolate exhibited some differences in physiology (no utilization of alcohols
      or carbohydrates) and genetic characteristics (low relatedness in DNA-DNA
      hybridization) as well as in its relation to light (differences in absorption
      wavelengths) from previously described Rhodobium species. Consequently, we
      propose that strain AR2102(T) (=DSM 17143(T)=ATCC BAA-1145(T)) should be
      considered as the type strain of a novel species within the genus Rhodobium,
      Rhodobium pfennigii sp. nov.

PMID- 17551039
TI  - Cellulomonas composti sp. nov., a cellulolytic bacterium isolated from cattle
      farm compost.
AB  - A bacterial strain, TR7-06(T), which has cellulase and beta-glucosidase
      activities, was isolated from compost at a cattle farm near Daejeon, Republic of
      Korea. It was a Gram-positive, aerobic or facultatively anaerobic, non-motile,
      rod-shaped bacterium. Phylogenetic analysis based on 16S rRNA gene sequences
      showed that this strain belongs to the genus Cellulomonas, with highest sequence
      similarity to Cellulomonas uda DSM 20107(T) (98.5 %). Cell wall analysis revealed
      the presence of type A4beta, L-orn-D-Glu peptidoglycan. The cell-wall sugars
      detected were mannose and glucose. The predominant menaquinone was MK-9(H(4)); MK
      8(H(4)) was detected in smaller quantities. The major fatty acids were anteiso
      C(15 : 0), C(16 : 0), C(14 : 0) and C(18 : 0). The polar lipids detected were
      diphosphatidylglycerol, phosphatidylethanolamine and phosphatidylinositol. The
      results of DNA-DNA hybridization and physiological and biochemical tests clearly
      demonstrated that TR7-06(T) represents a novel species. The combined genotypic
      and phenotypic data show that strain TR7-06(T) (=KCTC 19030(T)=NBRC 100758(T))
      merits description as the type strain of a novel Cellulomonas species,
      Cellulomonas composti sp. nov.

PMID- 17551040
TI  - Marichromatium bheemlicum sp. nov., a non-diazotrophic, photosynthetic
      gammaproteobacterium from a marine aquaculture pond.
AB  - A rod-shaped, phototrophic, purple sulfur bacterium, strain JA124(T), was
      isolated in pure culture from a marine aquaculture pond, located near
      Bhimunipatnam, in a medium that contained 3 % NaCl (w/v). Strain JA124(T) is a
      Gram-negative, motile rod with a single polar flagellum. Strain JA124(T) has a
      requirement for NaCl, with optimum growth at 1.5-8.5 %, and tolerates up to 11 %
      NaCl. Intracellular photosynthetic membranes are of the vesicular type.
      Bacteriochlorophyll a and probably carotenoids of the spirilloxanthin series are
      present as photosynthetic pigments. Strain JA124(T) was able to utilize sulfide,
      sulfate, thiosulfate, sulfite, thioglycollate and cysteine as sulfur sources.
      Strain JA124(T) was able to grow photolithoautotrophically,
      photolithoheterotrophically and photo-organoheterotrophically. Chemotrophic and
      fermentative growth could not be demonstrated. Strain JA124(T) lacks diazotrophic
      growth and acetylene reduction activity. Pyridoxal phosphate is required for
      growth. During growth on reduced sulfur sources as electron donors, sulfur is
      deposited intermediately as a number of small granules within the cell.
      Phylogenetic analysis on the basis of 16S rRNA gene sequences showed that strain
      JA124(T) clusters with species of the genus Marichromatium belonging to the class
      Gammaproteobacteria. The highest sequence similarities of strain JA124(T) were
      found with the type strains of Marichromatium indicum (98 %), Marichromatium
      purpuratum (95 %) and Marichromatium gracile (93 %). However, DNA-DNA
      hybridization with Marichromatium indicum DSM 15907(T) revealed relatedness of
      only 65 % with strain JA124(T). The DNA base composition of strain JA124(T) was
      67 mol% G+C (by HPLC). Based on 16S rRNA gene sequence analysis, morphological
      and physiological characteristics and DNA-DNA hybridization studies, strain
      JA124(T) (=ATCC BAA-1316(T)=JCM 13911(T)) is sufficiently different from other
      Marichromatium species to merit its description as the type strain of a novel
      species, Marichromatium bheemlicum sp. nov.

PMID- 17551041
TI  - Planococcus columbae sp. nov., isolated from pigeon faeces.
AB  - An orange-pigmented, Gram-positive bacterial strain, designated PgEx11(T), was
      isolated from pigeon faeces. Analysis of the 16S rRNA gene sequence of the
      isolate indicated that it had 94.2-98.2 % sequence identity with respect to those
      of seven recognized species of the genus Planococcus. The strain PgEx11(T)
      contained anteiso-C(15 : 0) as a major cellular fatty acid and MK-7 and MK-8 as
      the major menaquinones. The DNA G+C content of strain PgEx11(T) was 50.5 mol%.
      Furthermore, analysis of the 16S rRNA gene sequence indicated high levels of
      similarity with Planococcus rifietoensis (98.2 %), Planococcus maitriensis (97.6
      %), Planococcus citreus (97.5 %) and Planococcus maritimus (97.1 %). However, the
      mean value for DNA-DNA relatedness between PgEx11(T) and these four closely
      related species was in the range 45.4-16.8 %, respectively. Moreover, strain
      PgEx11(T) also differs from its close relatives with regard to biochemical and
      chemotaxonomic characteristics. On the basis of phenotypic, chemotaxonomic and
      genotypic differences, strain PgEx11(T) represents a novel species of the genus
      Planococcus, for which the name Planococcus columbae sp. nov. is proposed. The
      type strain is PgEx11(T) (=MTCC 7251(T)=DSM 17517(T)).

PMID- 17551042
TI  - Streptococcus orisuis sp. nov., isolated from the pig oral cavity.
AB  - Five bacterial strains, designated as NUM 1001(T), NUM 1002, NUM 1003, NUM 1004
      and NUM 1005, were isolated from the oral cavities of pigs. Colonies grown on
      mitis salivarius agar were similar in morphology to those of mutans streptococci.
      The novel isolates were analysed biochemically using the Rapid ID 32 Strep
      microsystem, subjected to DNA-DNA hybridization with oral streptococci and had
      their 16S rRNA genes sequenced. On the basis of the phylogenetic and phenotypic
      evidence obtained, the strains represent a novel species of the genus
      Streptococcus, for which the name Streptococcus orisuis sp. nov. is proposed. The
      type strain is NUM 1001(T) (=JCM 14035(T)=DSM 18307(T)).

PMID- 17551043
TI  - Proposal of six species of moderately thermophilic, acidophilic, endospore
      forming bacteria: Alicyclobacillus contaminans sp. nov., Alicyclobacillus
      fastidiosus sp. nov., Alicyclobacillus kakegawensis sp. nov., Alicyclobacillus
      macrosporangiidus sp. nov., Alicyclobacillus sacchari sp. nov. and
      Alicyclobacillus shizuokensis sp. nov.
AB  - Moderately thermophilic, acidophilic, spore-forming bacteria (146 strains) were
      isolated from various beverages and environments. Based on the results of
      sequence analysis of the hypervariable region of the 16S rRNA gene, eight of the
      strains represent novel species of the genus Alicyclobacillus. These strains were
      designated 3-A191(T), 4-A336(T), 5-A83J(T), 5-A167N, 5-A239-2O-A(T), E-8,
      RB718(T) and S-TAB(T). Phylogenetic analyses of 16S rRNA and DNA gyrase B subunit
      (gyrB) nucleotide sequences confirmed that the eight strains belonged to the
      Alicyclobacillus clade. Cells of the eight strains were Gram-positive or Gram
      variable, strictly aerobic and rod-shaped. The strains grew well under acidic and
      moderately thermal conditions, produced acid from various sugars, contained
      menaquinone 7 as the major isoprenoid quinone and did not produce guaiacol. omega
      Alicyclic fatty acids were the predominant lipid component of strains 4-A336(T),
      5-A83J(T), 5-A167N, RB718(T) and S-TAB(T). No omega-alicyclic fatty acids were
      detected in strains 3-A191(T), 5-A239-2O-A(T) or E-8, but iso- and anteiso
      branched fatty acids and small amounts of straight-chain saturated fatty acids
      were detected instead. According to the DNA-DNA hybridization data and distinct
      morphological, physiological, chemotaxonomical and genetic traits, the eight
      strains represent six novel species within the genus Alicyclobacillus, for which
      the following names are proposed: Alicyclobacillus contaminans sp. nov. (type
      strain 3-A191(T)=DSM 17975(T)=IAM 15224(T)), Alicyclobacillus fastidiosus sp.
      nov. (type strain S-TAB(T)=DSM 17978(T)=IAM 15229(T)), Alicyclobacillus
      kakegawensis sp. nov. (type strain 5-A83J(T)=DSM 17979(T)=IAM 15227(T)),
      Alicyclobacillus macrosporangiidus sp. nov. (type strain 5-A239-2O-A(T)=DSM
      17980(T)=IAM 15370(T)), Alicyclobacillus sacchari sp. nov. (type strain
      RB718(T)=DSM 17974(T)=IAM 15230(T)) and Alicyclobacillus shizuokensis sp. nov.
      (type strain 4-A336(T)=DSM 17981(T)=IAM 15226(T)).

PMID- 17551044
TI  - Reclassification of Pseudomonas aurantiaca as a synonym of Pseudomonas
      chlororaphis and proposal of three subspecies, P. chlororaphis subsp.
      chlororaphis subsp. nov., P. chlororaphis subsp. aureofaciens subsp. nov., comb.
      nov. and P. chlororaphis subsp. aurantiaca subsp. nov., comb. nov.
AB  - Pseudomonas chlororaphis, Pseudomonas aureofaciens and Pseudomonas aurantiaca
      were considered as separate species until 1989, when P. aureofaciens was proposed
      as a later heterotypic synonym of P. chlororaphis with P. aurantiaca remaining as
      a separate species. Nevertheless, analysis of the almost complete 16S rRNA gene
      sequences revealed that the type strain of P. aurantiaca, NCIMB 10068(T), shows
      gene sequence similarities close to 99.5 % with respect to P. chlororaphis DSM
      50083(T) and P. aureofaciens DSM 6698(T). DNA-DNA hybridization experiments among
      strains of P. aurantiaca, P. chlororaphis and P. aureofaciens showed values
      higher than 70 %, confirming that they represent members of the same species. The
      results of fatty acid analysis and phenotypic traits showed that these strains
      are closely related, although there are some differences among the strains
      belonging to P. aurantiaca, those from P. chlororaphis and those from P.
      aureofaciens. All these results confirm the previous reclassification of P.
      aureofaciens into P. chlororaphis and support the reclassification of P.
      aurantiaca as a synonym of P. chlororaphis. Phenotypic and molecular data permit
      the description of three novel subspecies within this last species, for which the
      following names are proposed: P. chlororaphis subsp. chlororaphis subsp. nov.
      [with the type strain DSM 50083(T) (=ATCC 9446(T)=NCIMB 9392(T))], P.
      chlororaphis subsp. aureofaciens subsp. nov., comb. nov. [with the type strain
      DSM 6698(T) (=ATCC 13985(T)=NCIMB 9030(T))] and P. chlororaphis subsp. aurantiaca
      subsp. nov., comb. nov. [with the type strain NCIMB 10068(T) (=ATCC 33663(T)=CIP
      106718(T))].

PMID- 17551045
TI  - Aerococcus suis sp. nov., isolated from clinical specimens from swine.
AB  - Biochemical and molecular genetic studies were performed for five isolates of
      unknown Gram-positive, catalase-negative, cocci-shaped micro-organisms obtained
      from clinical samples from pigs. The micro-organisms were tentatively identified
      as Aerococcus species on the basis of the results from cellular morphological and
      biochemical tests. 16S rRNA gene sequencing studies confirmed the provisional
      identification of the isolates as members of the genus Aerococcus, but the micro
      organism did not correspond to any recognized species of this genus. The nearest
      phylogenetic relatives of these unknown cocci isolated from pigs were Aerococcus
      viridans (95.9 % 16S rRNA gene sequence similarity) and Aerococcus urinaeequi
      (95.8 %). The unknown bacterium, however, was distinguishable from these two
      species and from other animal aerococci by using biochemical tests. On the basis
      of both phenotypic and phylogenetic findings, the isolates represent a novel
      species of the genus Aerococcus, for which the name Aerococcus suis sp. nov. is
      proposed. The type strain is 1821/02(T) (=CECT 7139(T)=CCUG 52530(T)).

PMID- 17551046
TI  - Aquincola tertiaricarbonis gen. nov., sp. nov., a tertiary butyl moiety-degrading
      bacterium.
AB  - Strains L10(T), L108 and CIP I-2052 were originally obtained from methyl tert
      butyl ether (MTBE)-contaminated groundwater and from a wastewater treatment
      plant, respectively. All share the ability to grow on tert-butanol, an
      intermediate of MTBE degradation. Cells are strictly aerobic, motile by a polar
      flagellum and exhibit strong pili formation. Poly beta-hydroxybutyrate (PHB)
      granules are formed. The DNA G+C content is 69-70.5 mol% and the main ubiquinone
      is Q-8. The major cellular fatty acids are 16 : 1 cis-9 and 16 : 0 and the only
      hydroxy fatty acid is 10 : 0 3-OH. The major phospholipids are
      phosphatidylethanolamine (PE) 16 : 1/16 : 1 and phosphatidylglycerol 16 : 0/16 :
      1. A significant amount of PE 17 : 0/16 : 1 is present. The 16S rRNA gene
      sequences of these strains are almost identical and form a separate line of
      descent in the Rubrivivax-Roseateles-Leptothrix-Ideonella-Aquabacterium branch of
      the Betaproteobacteria with 97 % similarity to 16S rRNA genes of the type strains
      of Rubrivivax gelatinosus, Leptothrix mobilis and Ideonella dechloratans.
      However, physiological properties, DNA-DNA relatedness values and the
      phospholipid and cellular fatty acid profiles distinguish the novel isolates from
      the three closely related genera. Therefore, it is concluded that strains L10(T),
      L108 and CIP I-2052 represent a new genus and novel species for which the name
      Aquincola tertiaricarbonis gen. nov., sp. nov., is proposed. The type strain is
      strain L10(T) (=DSM 18512(T)=CIP 109243(T)).

PMID- 17551047
TI  - Ruegeria mobilis sp. nov., a member of the Alphaproteobacteria isolated in Japan
      and Palau.
AB  - The taxonomic positions of two bacterial strains, MBIC01146(T) and MBIC01099,
      isolated from marine environments of Japan and Palau, respectively, were
      determined by using a polyphasic approach. The bacteria were aerobic, motile,
      Gram-negative rods and formed star-shaped aggregations. The G+C content of the
      genomic DNA ranged from 58.5 to 58.7 mol%. The major respiratory quinone was
      ubiquinone-10 and the predominant cellular fatty acids were C(16 : 0), C(18 :
      1)omega6c and C(18 : 1)omega7c. 16S rRNA gene sequence analyses based on both
      neighbour-joining and maximum-parsimony methods revealed that strains
      MBIC01146(T) and MBIC01099 were positioned within the cluster comprising Ruegeria
      atlantica and Silicibacter lacuscaerulensis within subgroup alpha-3 of the
      Proteobacteria. The phenotypic and chemotaxonomic characteristics of the novel
      strains were similar to those of Ruegeria atlantica; however, DNA-DNA
      hybridization tests showed that the isolates represented an independent species.
      The isolates could be differentiated from Ruegeria atlantica based on several
      characteristics. Therefore, strains MBIC01146(T) and MBIC01099 are considered to
      represent a novel species of the genus Ruegeria, for which the name Ruegeria
      mobilis sp. nov. is proposed. The type strain is MBIC01146(T) (=NBRC
      101030(T)=CIP 109181(T)). An emended description of Ruegeria atlantica Uchino et
      al. 1999 is also given.

PMID- 17551048
TI  - Devosia insulae sp. nov., isolated from soil, and emended description of the
      genus Devosia.
AB  - A Gram-negative, motile, aerobic and oval- or rod-shaped bacterial strain, DS
      56(T), which is phylogenetically closely related to the genus Devosia, was
      isolated from soil from Dokdo, Korea. Strain DS-56(T) grew optimally at pH 6.5
      7.5 and 25 degrees C in the presence of 0.5 % (w/v) NaCl. A neighbour-joining
      phylogenetic tree based on 16S rRNA gene sequences showed that strain DS-56(T)
      joins the cluster comprising Devosia species, at a bootstrap resampling value of
      100 %. The levels of 16S rRNA gene sequence similarity between strain DS-56(T)
      and the type strains of recognized Devosia species ranged from 95.4 to 96.4 %.
      Strain DS-56(T) contained Q-11 as the predominant ubiquinone, unlike Devosia
      species, which contain Q-10 as the predominant ubiquinone. The novel strain also
      contained some fatty acids, including branched and hydroxy fatty acids, that are
      not detected in Devosia species. The DNA G+C content of strain DS-56(T) was 66.2
      mol%. On the basis of the phenotypic, chemotaxonomic and phylogenetic data,
      strain DS-56(T) represents a novel species of the genus Devosia, for which the
      name Devosia insulae sp. nov. is proposed. The type strain is DS-56(T) (=KCTC
      12821(T)=DSM 17955(T)).

PMID- 17551049
TI  - Clostridium aestuarii sp. nov., from tidal flat sediment.
AB  - A strictly anaerobic, halophilic, motile, endospore-forming, rod-shaped
      bacterium, designated strain HY-45-18(T), was isolated from a sediment sample of
      a tidal flat in Korea. The isolate produced butyric acid, propionic acid,
      glycerol and H(2) as fermentation end products from glucose. Strain HY-45-18(T)
      is halophilic as it was unable to grow in the absence of sea salts. A 16S rRNA
      gene sequence analysis clearly indicated that the tidal flat isolate is a member
      of cluster I of the order Clostridiales, which contains the type species of
      Clostridium, Clostridium butyricum. The closest phylogenetic neighbour of strain
      HY-45-18(T) was Clostridium ganghwense KCTC 5146(T) (96.5 % 16S rRNA gene
      sequence similarity). Several phenotypic characteristics can be readily used to
      differentiate the isolate from phylogenetically related clostridia. Therefore,
      strain HY-45-18(T) represents a novel species of the genus Clostridium, for which
      the name Clostridium aestuarii sp. nov. is proposed. The type strain is HY-45
      18(T) (=IMSNU 40129(T)=KCTC 5147(T)=JCM 13194(T)).

PMID- 17551050
TI  - 'Candidatus Magnetoglobus multicellularis', a multicellular, magnetotactic
      prokaryote from a hypersaline environment.
AB  - Phylogenetic analysis and phenotypic characterization were used to assign a
      multicellular magnetotactic prokaryote the name 'Candidatus Magnetoglobus
      multicellularis'. 'Candidatus Magnetoglobus multicellularis' lives in a large
      hypersaline coastal lagoon from Brazil and has properties that are unique among
      prokaryotes. It consists of a compact assembly or aggregate of flagellated
      bacterial cells, highly organized in a sphere, that swim in either helical or
      straight trajectories. The life cycle of 'Candidatus Magnetoglobus
      multicellularis' is completely multicellular, in which one aggregate grows by
      enlarging the size of its cells and approximately doubling the volume of the
      whole organism. Cells then divide synchronously, maintaining the spherical
      arrangement; finally the cells separate into two identical aggregates.
      Phylogenetic 16S rRNA gene sequence analysis showed that 'Candidatus
      Magnetoglobus multicellularis' is related to the dissimilatory sulfate-reducing
      bacteria within the Deltaproteobacteria and to other previously described, but
      not yet well characterized, multicellular magnetotactic prokaryotes.

PMID- 17551051
TI  - Bacteroides coprophilus sp. nov., isolated from human faeces.
AB  - Three Gram-negative, anaerobic, rod-shaped bacteria (strains CB40, CB41 and
      CB42(T)) were isolated from human faeces. Based on phylogenetic analysis and
      specific phenotypic characteristics, these strains were included in the genus
      Bacteroides, and 16S rRNA gene sequence analysis indicated that these strains
      represented a novel species. The strains were most closely related to the type
      strains of Bacteroides barnesiae and Bacteroides salanitronis, with sequence
      similarities of 93.4 and 89.8 %, respectively. The G+C content of strain CB42(T)
      is 44.7 mol%. Major fatty acids were anteiso-C(15 : 0), C(16 : 0), iso-C(17 : 0)
      3-OH and C(18 : 1)omega9c. On the basis of the data presented, a novel
      Bacteroides species, Bacteroides coprophilus sp. nov., is proposed, with CB42(T)
      (=JCM 13818(T)=DSM 18228(T)) as the type strain.

PMID- 17551052
TI  - Flammeovirga kamogawensis sp. nov., isolated from coastal seawater in Japan.
AB  - Two strains of gliding, agarolytic bacteria, strains YS10(T) and YML5, were
      isolated from coastal seawater off Kamogawa, Japan. Phylogenetic analysis based
      on 16S rRNA gene sequences showed that the novel isolates represent a separate
      lineage within the genus Flammeovirga. DNA-DNA hybridization values between these
      isolates and the type strains of species of the genus Flammeovirga were
      significantly lower than those accepted as threshold values for the phylogenetic
      definition of a species. Furthermore, some of the phenotypic characteristics
      indicate that the isolates differ from other Flammeovirga species. Based on these
      differences, it is suggested that the isolates represent a novel species, for
      which the name Flammeovirga kamogawensis sp. nov. is proposed. The type strain is
      YS10(T) (=IAM 15451(T)=NCIMB 14281(T)).

PMID- 17551053
TI  - Alcanivorax balearicus sp. nov., isolated from Lake Martel.
AB  - A bacterial strain designated MACL04(T) was isolated from Lake Martel, a
      subterraneous saline lake in Mallorca (Spain). The complete 16S rRNA gene
      sequence of this strain showed nearly 100 % similarity to that of Alcanivorax
      dieselolei B-5(T). Despite this high similarity, strain MACL04(T) showed
      phenotypic, chemotaxonomic and molecular differences with respect to A.
      dieselolei, indicating that strain MACL04(T) represents a separate species. Cells
      of strain MACL04(T) were motile by means of a single polar or subpolar flagellum
      and colonies formed on media containing 1 % (v/v) Tween 20 were opaque and
      mucoid, with blue-green iridescence. The generation time of strain MACL04(T) in
      this medium was approximately half that of A. dieselolei B-5(T) and strain
      MACL04(T) did not produce lipases after incubation for 5 days. Strain MACL04(T)
      did not require NaCl for growth and grew in the presence of up to 15 % (w/v)
      NaCl. The strain was able to use alkanes as a sole carbon source; however,
      glucose could also be used, albeit weakly, as a carbon source. Several amino
      acids and organic acids were used as carbon sources. Strain MACL04(T) produced
      acid in media containing pyruvate as the sole carbon source. The major fatty
      acids were C(19 : 0) cyclo omega8c and C(16 : 0). The fatty acid C(16 :
      1)omega8c, present in strain MACL04(T), was not detected in the recognized
      Alcanivorax species. The sequences of the large and short 16S-23S intergenic
      spacer regions showed similarities of 97.2 and 98.8 % (ungapped) with respect to
      A. dieselolei B-5(T). Partial sequences of gyrB and alkb genes showed 94.0 %
      similarity between strain MACL04(T) and A. dieselolei B-5(T). The G+C content of
      strain MACL04(T) was 62.8 mol%. The data from this polyphasic study indicate that
      strain MACL04(T) represents a novel species of the genus Alcanivorax, for which
      the name Alcanivorax balearicus sp. nov. is proposed. The type strain is
      MACL04(T) (=LMG 22508(T)=CECT 5683(T)).

PMID- 17551054
TI  - Parapedobacter koreensis gen. nov., sp. nov.
AB  - Strain Jip14(T), a Gram-negative, non-spore-forming, rod-shaped, non-motile
      bacterium, was isolated from dried rice straw and characterized in order to
      determine its taxonomic position. 16S rRNA gene sequence analysis revealed that
      strain Jip14(T) belongs to the family Sphingobacteriaceae, and the highest degree
      of sequence similarity was determined to be to Pedobacter saltans DSM 12145(T)
      (88.5 %), Pedobacter africanus DSM 12126(T) (87.6 %), Pedobacter heparinus DSM
      2366(T) (87.1 %) and Pedobacter caeni LMG 22862(T) (86.9 %). Chemotaxonomic data
      revealed that strain Jip14(T) possesses menaquinone MK-7 and the predominant
      fatty acids C(15 : 0) iso, C(16 : 0), C(16 : 0) 10-methyl, C(17 : 0) iso 3-OH and
      summed feature 3 (C(15 : 0) iso 2-OH/C(16 : 1)omega7c). The results of
      physiological and biochemical tests clearly demonstrated that strain Jip14(T)
      represents a distinct species. Based on these data, Jip14(T) should be classified
      within a novel genus and species, for which the name Parapedobacter koreensis
      gen. nov., sp. nov. is proposed. The type strain of Parapedobacter koreensis is
      Jip14(T) (=KCTC 12643(T)=LMG 23493(T)).

PMID- 17551055
TI  - Sphingomonas pseudosanguinis sp. nov., isolated from the water reservoir of an
      air humidifier.
AB  - A yellow-pigmented bacterial isolate, strain G1-2(T), obtained from the surface
      of an air humidifier, was characterized taxonomically. 16S rRNA gene sequence
      analysis, physiological characterization and estimation of the ubiquinone and
      polar lipid patterns and fatty acid composition revealed that strain G1-2(T) was
      similar to Sphingomonas yabuuchiae and Sphingomonas sanguinis, but also showed
      pronounced differences. On the basis of these results, a novel species of the
      genus Sphingomonas is described, for which the name Sphingomonas pseudosanguinis
      sp. nov. is proposed. The type strain is G1-2(T) (=CCUG 54232(T)=CIP 109431(T)).

PMID- 17551056
TI  - Paenibacillus fonticola sp. nov., isolated from a warm spring.
AB  - A novel bacterial strain, designated ZL(T), isolated from a warm spring in
      Jhonglun, Taiwan, was characterized by using a polyphasic taxonomic approach. The
      novel strain had chemotaxonomic and morphological properties consistent with its
      classification in the genus Paenibacillus. Cells were Gram-variable, aerobic,
      sporulating, motile rods. 16S rRNA gene sequence analysis demonstrated that this
      novel isolate was unique, showing 94.3 % sequence similarity to Paenibacillus
      assamensis GPTSA 11(T) and lower levels to Paenibacillus timonensis 2301032(T)
      (94.0 %), Paenibacillus macerans ATCC 8244(T) (93.3 %), Paenibacillus
      barengoltzii SAFN-016(T) (93.3 %) and Paenibacillus sanguinis 2301083(T) (93.2
      %). The novel isolate could be distinguished from the type strains of all of
      these species based on a range of phenotypic data. The major cellular
      phospholipids were phosphatidylglycerol, diphosphatidylglycerol,
      phosphatidylethanolamine and one unknown phosphoglycolipid. The predominant
      isoprenologue was an unsaturated menaquinone with seven isoprene units (MK-7).
      The major fatty acids of strain ZL(T) were C(16 : 0) (33.5 %), anteiso-C(15 : 0)
      (32.5 %) and iso-C(16 : 0) (9.3 %). The G+C content of the genomic DNA was 49.2
      mol%. It is evident from the genotypic and phenotypic data that strain ZL(T)
      should be classified as representing a novel species of the genus Paenibacillus,
      for which the name Paenibacillus fonticola sp. nov. is proposed. The type strain
      is ZL(T) (=BCRC 17579(T)=LMG 23577(T)).

PMID- 17551057
TI  - Paenibacillus taiwanensis sp. nov., isolated from soil in Taiwan.
AB  - Among a large collection of Taiwanese soil isolates, a novel Gram-variable, rod
      shaped, motile and endospore-forming bacterial strain, designated G-soil-2-3(T),
      was isolated from farmland soil in Wu-Feng, Taiwan. The isolate was subjected to
      a polyphasic study including 16S rRNA gene sequence analysis, DNA-DNA
      hybridization experiments, fatty acid analysis and comparative phenotypic
      characterization. 16S rRNA gene sequence analysis indicated that the organism
      belongs within the genus Paenibacillus. It contained menaquinone MK-7 as the
      predominant isoprenoid quinone and anteiso-C(15 : 0) (40.5 %), iso-C(15 : 0)
      (13.1 %), iso-C(16 : 0) (10.8 %) and anteiso-C(17 : 0) (7.3 %) as the major fatty
      acids. Phylogenetically, the closest relatives of strain G-soil-2-3(T) were the
      type strains of Paenibacillus assamensis, Paenibacillus alvei and Paenibacillus
      apiarius, with 16S rRNA gene sequence similarity of 95.7, 95 and 95.2 %,
      respectively. DNA-DNA hybridization experiments showed levels of relatedness of
      2.8-9.0 % of strain G-soil-2-3(T) with these strains. The G+C content of the DNA
      was 44.6 mol%. Strain G-soil-2-3(T) was clearly distinguishable from P.
      assamensis, P. alvei and P. apiarius and thus represents a novel species of the
      genus Paenibacillus, for which the name Paenibacillus taiwanensis sp. nov. is
      proposed. The type strain is G-soil-2-3(T) (=BCRC 17411(T)=IAM 15414(T)=LMG
      23799(T)=DSM 18679(T)).

PMID- 17551058
TI  - Chryseobacterium daeguense sp. nov., isolated from wastewater of a textile dye
      works.
AB  - A Gram-negative, rod-shaped bacterial strain, K105(T), was isolated from
      wastewater of a textile dye works in Korea and subjected to a polyphasic
      taxonomic study. Strain K105(T) grew optimally at pH 6.5-7.5 and 30-37 degrees C.
      It contained MK-6 as the predominant menaquinone and iso-C(15 : 0), iso-C(17 :
      1)omega9c, iso-C(17 : 0) 3-OH and summed feature 3 (C(16 : 1)omega7c and/or iso
      C(15 : 0) 2-OH) as the major fatty acids. The DNA G+C content was 36.8 mol%.
      Phylogenetic analysis based on 16S rRNA gene sequences showed that strain K105(T)
      belonged to the genus Chryseobacterium. Strain K105(T) exhibited 16S rRNA gene
      sequence similarity values of less than 96.9 % to the type strains of recognized
      Chryseobacterium species. Strain K105(T) differed from phylogenetically related
      Chryseobacterium species in several phenotypic properties. On the basis of
      phenotypic and phylogenetic data, strain K105(T) (=KCTC 12841(T)=JCM 14362(T)) is
      placed in the genus Chryseobacterium as the type strain of a novel species, for
      which the name Chryseobacterium daeguense sp. nov. is proposed.

PMID- 17551062
TI  - Histological and proteomic analysis of reversible H-RasV12G expression in
      transgenic mouse skin.
AB  - We have used a two-transgene tetracycline system to reversibly express oncogenic
      H-Ras(V12G) in mouse skin and primary keratinocytes culture using the bovine
      keratin 5 promoter. Induction of H-Ras(V12G) expression in skin at 30 days after
      birth causes epidermal basal cell hyperplasia, an eruption of keratinous cysts
      and loss of hair follicles by 3 weeks. Subsequent H-Ras(V12G) de-induction for 3
      days results in massive apoptosis in the non-H-Ras(V12G)-expressing stroma as
      well as in the suprabasal cells of the epidermis. Several procaspases such as
      CASP3, 1alpha, 5 and 12 disappeared, whereas the pro-apoptotic proteins AIF, Bax
      and Fas ligand were induced in H-Ras(V12G) de-induction skin. This process is
      followed by a wave of cell division at 14 days as hair follicles regrew,
      returning to near normal histology and skin appearance by 30 days. Using
      Kinetworkstrade mark multi-immunoblotting screens, the phosphorylation status of
      37 proteins and expression levels of 75 protein kinases in the skin were
      determined in three samples: (i) wild-type skin, (ii) hyperplastic H-Ras(V12G)
      expressing skin and (iii) skin where H-Ras(V12G) expression was suppressed for 7
      days. Following H-Ras(V12G) induction, 16 kinases were increased over 2-fold, and
      2 kinases were reduced over 50%. This included increased phosphorylation of both
      known downstream H-Ras(V12G) targets and unknown H-Ras(V12G) targets. After H
      Ras(V12G) suppression, many but not all protein changes were reversed. These
      results from skin and primary keratinocytes are organized to reflect the
      molecular events that cause the histological changes observed. These proteomic
      changes identify markers that may mediate the oncogenic addiction paradigm.

PMID- 17551059
TI  - Psychromonas hadalis sp. nov., a novel piezophilic bacterium isolated from the
      bottom of the Japan Trench.
AB  - An obligately piezophilic bacterium was isolated from sediment collected from the
      bottom of the Japan Trench at a depth of 7542 m. The isolated strain, designated
      K41G(T), was closely affiliated with members of the genus Psychromonas on the
      basis of 16S rRNA gene sequence analysis. Levels of DNA-DNA relatedness between
      strain K41G(T) and Psychromonas reference strains were significantly lower than
      that accepted as the phylogenetic definition of a species. The optimal
      temperature and pressure for growth of strain K41G(T) were 6 degrees C and 60
      MPa, respectively. The DNA G+C content was 39.1 mol%. Whole-cell fatty acids
      consisted of significant amounts of unsaturated fatty acids C(16 : 1) (37 %) and
      C(14 : 1) (17 %), saturated fatty acid C(16 : 0) (31 %) and polyunsaturated fatty
      acid C(22 : 6) (8 %). Based on the taxonomic differences observed, strain K41G(T)
      is considered to represent a novel obligately piezophilic Psychromonas species.
      The name Psychromonas hadalis (type strain, K41G(T)=JCM 11830(T)=ATCC BAA-638(T))
      is proposed. This is the second species of obligately piezophilic bacteria to be
      proposed in the genus Psychromonas.

PMID- 17551063
TI  - Sulfasalazine-induced immune thrombocytopenia.
AB  - Sulfasalazine is a well established disease-modifying anti-rheumatic drug
      commonly used in the treatment of rheumatic disorders and inflammatory bowel
      disease. Sulfasalazine was generally well tolerated in clinical trials, the most
      frequently reported adverse effects being adverse gastrointestinal effects,
      headache, dizziness and rash; myelosuppression can also occur. We are now
      reporting the first case of autoimmune thrombocytosis following sulfasalazine
      treatment.

PMID- 17551064
TI  - Shared learning in the National Health Service.

PMID- 17551065
TI  - Forget me not: palliative care for people with dementia.
AB  - Dementia is a progressive life limiting condition with increasing prevalence and
      complex needs. Palliative care needs of patients with dementia are often poorly
      addressed; symptoms such as pain are under treated while these patients are over
      subjected to burdensome interventions. Research into palliative care in dementia
      remains limited but recent developments together with national guidelines and
      policies set foundations for improving the delivery of palliative care to this
      group of the population.

PMID- 17551066
TI  - Endoscopic mucosal resection of Barrett's oesophagus containing dysplasia or
      intramucosal cancer.
AB  - Barrett's oesophagus is premalignant. Oesophagectomy is traditionally regarded as
      the standard treatment option in the presence of high grade intraepithelial
      neoplasia or intramucosal cancer. However, oesophagectomy is associated with high
      rates of mortality and morbidity. Endoscopic ablative therapies are limited by
      the lack of tissue for histological assessment, and the ablation may be
      incomplete. Endoscopic mucosal resection is an alternative to surgery in the
      management of high grade intraepithelial neoplasia and intramucosal cancer. It is
      less invasive than surgery and, unlike ablative treatments, provides tissue for
      histological assessment. This review will cover the indications, techniques and
      results of endoscopic mucosal resection.

PMID- 17551067
TI  - Hyponatraemia in clinical practice.
AB  - Hyponatraemia is defined as a serum sodium concentration below 135 mmol/l. It
      causes major diagnostic and management problems in practice. Hyponatraemic
      disorders are divided into euvolaemic, hypervolaemic and hypovolaemic. In the
      evaluation of the hyponatraemic patient, history taking should focus on
      identifying the potential cause, duration and symptomatology. Clinical
      examination should include assessment of volume status. Acute hyponatraemia of
      less than 48 h duration requires prompt correction. Treatment may involve
      hypertonic saline, isotonic saline and appropriate hormone replacement therapy
      depending on the aetiology. Chronic hyponatraemia should be treated with caution
      because of the risk of central pontine myelinolysis.

PMID- 17551068
TI  - Spontaneous bacterial peritonitis.
AB  - Spontaneous bacterial peritonitis (SBP) is the infection of ascitic fluid in the
      absence of any intra-abdominal, surgically treatable source of infection. Despite
      timely diagnosis and treatment its reported incidence in ascitic patients varies
      between 7-30%. Ascitic paracentesis remains the chief diagnostic procedure.
      Automated cell counters have the same diagnostic accuracy as the manual
      measurement of white cells. Lately, the use of leucocyte reagent strips
      (dipsticks) has emerged as a useful alternative. Examination of the fluid is not
      complete unless the sample is inoculated in blood culture bottles. Treatment is
      currently with third-generation cephalosporins or oral quinolones. Following a
      single episode of SBP patients should have long term antibiotic prophylaxis.

PMID- 17551069
TI  - Levodopa-induced dyskinesia in Parkinson's disease: clinical features,
      pathogenesis, prevention and treatment.
AB  - Levodopa is the most effective drug for treating Parkinson's disease. However,
      long-term use of levodopa is often complicated by significantly disabling
      fluctuations and dyskinesias negating its beneficial effects. Younger age of
      Parkinson's disease onset, disease severity, and high levodopa dose increase the
      risk of development of levodopa-induced dyskinesias (LID). The underlying
      mechanisms for LID are unclear though recent studies indicate the importance of
      pulsatile stimulation of striatal postsynaptic receptors in their pathogenesis.
      The non-human primates with MPTP-induced parkinsonism serve as a useful model to
      study dyskinesia. Once established, LID are difficult to treat and therefore
      efforts should be made to prevent them. The therapeutic and preventative
      strategies for LID include using a lower dosage of levodopa, employing dopamine
      agonists as initial therapy in Parkinson's disease, amantadine, atypical
      neuroleptics, and neurosurgery. LID can adversely affect the quality of life and
      increase the cost of healthcare.

PMID- 17551070
TI  - Cocaine use and stroke.
AB  - Stroke is the third most common cause of death in developed countries. In England
      and Wales, 1000 people under the age of 30 have a stroke each year. Cocaine is
      the most commonly used class A drug, and the first report of cocaine-induced
      stroke was in 1977. Since the development of alkaloidal "crack" cocaine in the
      1980s, there has been a significant rise in the number of case reports describing
      both ischaemic and haemorrhagic stroke associated with cocaine use. Cocaine is a
      potent central nervous system stimulant, and acts by binding to specific
      receptors at pre-synaptic sites preventing the reuptake of neurotransmitters. The
      exact mechanism of cocaine-induced stroke remains unclear and there are likely to
      be a number of factors involved including vasospasm, cerebral vasculitis,
      enhanced platelet aggregation, cardioembolism, and hypertensive surges associated
      with altered cerebral autoregulation. The evidence surrounding each of these
      factors will be considered here.

PMID- 17551071
TI  - Management of end stage cardiac failure.
AB  - Optimum heart failure medication and an increasing array of interventions have
      had an enormous effect on morbidity and mortality over the past 10 years.
      However, patients with end stage disease can still be highly symptomatic.
      Moreover, such patients are disadvantaged compared with patients with malignant
      disease. They are less likely to have an understanding of their illness or have
      access to supportive care. They are also less likely to have the opportunity to
      plan for care with regard to death and dying. There is increasing demand that the
      multi-professional clinical team gain good communication and supportive care
      skills, and that appropriate access to specialist palliative care services is
      available.

PMID- 17551072
TI  - Acute rhinosinusitis in adults: an update on current management.
AB  - Acute rhinosinusitis is a common disease with worldwide prevalence. It is a
      significant burden on the health services. It is most commonly caused by viruses
      and is self-limiting in nature. The diagnosis of acute rhinosinusitis is clinical
      and sinus radiography is not indicated routinely. Most cases of acute
      rhinosinusitis are treated symptomatically. However, symptoms may persist beyond
      10 days when secondary bacterial infection prevails. Antibiotics are reserved for
      moderate or severe cases or when there is development of complications of acute
      rhinosinusitis. This paper provides an update on the current management of acute
      rhinosinusitis.

PMID- 17551073
TI  - Larval therapy from antiquity to the present day: mechanisms of action, clinical
      applications and future potential.
AB  - When modern medicine fails, it is often useful to draw ideas from ancient
      treatments. The therapeutic use of fly larvae to debride necrotic tissue, also
      known as larval therapy, maggot debridement therapy or biosurgery, dates back to
      the beginnings of civilisation. Despite repeatedly falling out of favour largely
      because of patient intolerance to the treatment, the practice of larval therapy
      is increasing around the world because of its efficacy, safety and simplicity.
      Clinical indications for larval treatment are varied, but, in particular, are
      wounds infected with multidrug-resistant bacteria and the presence of significant
      co-morbidities precluding surgical intervention. The flies most often used in
      larval therapy are the facultative calliphorids, with the greenbottle blowfly
      (Lucilia sericata) being the most widely used species. This review summarises the
      fascinating and turbulent history of larval therapy from its origin to the
      present day, including mechanisms of action and evidence for its clinical
      applications. It also explores future research directions.

PMID- 17551074
TI  - Peroxisome proliferator-activated receptor gamma agonists inhibit the
      proliferation and invasion of human colon cancer cells.
AB  - BACKGROUND AND AIMS: Data regarding the effect of peroxisome proliferator
      activated receptor gamma (PPAR-gamma) ligands on the invasive ability of colon
      cancer cells are currently limited. This study was designed to examine the
      effects of PPAR-gamma agonists on the proliferation and invasion of two colon
      cancer cells to identify the role of PPAR-gamma in colon cancer growth and
      metastasis. METHODS: SW480 and LS174T cells were treated with PPAR-gamma ligands,
      pioglitazone and 15-deoxy-delta(12,14)-prostaglandin J2 (15d-PGJ2), as well as
      their combinations with the PPAR-gamma antagonist GW9662. MTT assay was used to
      determine the antiproliferative effects. Cell cycle analysis was conducted by
      flow cytometry. The mRNA and protein expression were detected by reverse
      transcriptase polymerase chain reaction (RT-PCR) and western blot, respectively.
      The invasive ability of cells was determined by the BD BioCoat Matrige invasion
      chamber. RESULTS: Pioglitazone and 15d-PGJ2 inhibited the proliferation of both
      colon cancer cell lines in a dose-dependent manner. This growth inhibitory effect
      was reversed by GW9662. Results from flow cytometry demonstrated G1 arrest
      following treatment with pioglitazone and 15d-PGJ2. The expression of matrix
      metalloproteinase-7 (MMP-7) was only detected in LS174T cells, while its tissue
      inhibitor-1 (TIMP-1) was expressed in both colon cancer cells. 15d-PGJ2 and
      pioglitazone downregulated MMP-7 expression and upregulated TIMP-1 expression.
      PPAR-gamma agonists can only inhibit invasive activity of LS174T cells.
      CONCLUSIONS: PPAR-gamma agonists have inhibitory effects on the proliferation of
      colon cancer cell lines associated with G1 cell cycle arrest and invasive
      activity. The latter effect is demonstrated in certain cell lines through the
      down-regulation of MMP-7 synthesis.

PMID- 17551075
TI  - Screening for Addison's disease in patients with type 1 diabetes mellitus and
      recurrent hypoglycaemia.
AB  - BACKGROUND: Addison's disease may present with recurrent hypoglycaemia in
      subjects with type 1 diabetes mellitus. There are no data, however, on the
      prevalence of Addison's disease presenting with recurrent hypoglycaemia in
      patients with diabetes mellitus. METHODS: Three year retrospective study of
      diabetic patients with "unexplained" recurrent hypoglycaemia investigated with a
      short Synacthen test to exclude adrenocortical insufficiency. RESULTS: 95
      patients with type 1 diabetes mellitus were studied. Addison's disease was
      identified as the cause of recurrent hypoglycaemia in one patient with type 1
      diabetes mellitus. CONCLUSION: Addison's disease is a relatively rare but
      remedial cause of recurrent hypoglycaemia in patients with type 1 diabetes
      mellitus. A low threshold for investigating patients with type 1 diabetes
      mellitus and recurrent hypoglycaemia to detect Addison's disease is therefore
      suggested.

PMID- 17551076
TI  - Effect of serum creatine kinase-MBmass on the early and hierarchical diagnosis of
      related artery reperfusion in acute myocardial infarction.
AB  - AIM: To evaluate creatine kinase-MBmass (CK-MBmass) for the early diagnosis of
      infarct-related artery (IRA) patency after thrombolysis and the hierarchical
      diagnosis of related artery reperfusion (RAR). PATIENTS AND METHODS: CK-MBmass
      and creatine kinase-MBactivity (CK-MBactivity) were measured kinetically in 48
      patients treated with thrombolysis and 96 patients treated with routine drugs.
      RESULTS: In the continuous-RAR (CRAR) group, the peak values of CK-MBmass and CK
      MBactivity appeared at < or =12 h, the peak durations were maintained for < or =8
      h before decreasing to normal at < or =42 h, which occurred more quickly than
      those values in the non-RAR (NRAR) group. In the temporary-RAR (TRAR) group, the
      peak values appeared at < or =12 h, but no significant differences were found
      between the TRAR and NRAR groups in the time that the peak durations lasted
      before decreasing to normal values. In the reobliteration group after RAR, the
      peak values appeared at < or =12 h, and the peak durations were maintained for <
      or =8 h. After returning to the normal, a second peak appeared, and the time
      required for the values to return to normal was prolonged significantly.
      CONCLUSIONS: CK-MBmass could be used as an indicator of RAR after thrombolysis;
      and the kinetic changes of serum CK-MBmass could be used for the hierarchical
      diagnosis of RAR in acute myocardial infarction.

PMID- 17551077
TI  - Long term prognosis of women with gestational diabetes in a multiethnic
      population.
AB  - AIM: To assess the glucose tolerance of South Asian and Caucasian women with
      previous gestational diabetes mellitus (GDM). METHOD: A retrospective follow-up
      study of 189 women diagnosed with GDM between 1995 and 2001. Glucose tolerance
      was reassessed by oral glucose tolerance test at a mean duration since pregnancy
      of 4.38 years. RESULTS: South Asian women comprised 65% of the GDM population.
      Diabetes developed in 36.9% of the population, affecting more South Asian (48.6%)
      than Caucasian women (25.0%). Women developing diabetes were older at follow-up
      (mean (SD) 38.8 (5.7) vs 35.9 (5.6) years; p<0.05) and had been heavier (body
      mass index 31.4 (6.3) vs 27.7 (6.7) kg/m(2); p<0.05), more hyperglycaemic (Gl(0)
      6.5 (1.7) vs 5.2 (1.1) mmol/l; p<0.01: G(120) 11.4 (3.3) vs 9.6 (1.8) mmol/l;
      p<0.01: HbA1c 6.4 (1.0) vs 5.6 (0.7); p<0.01) and more likely to require insulin
      during pregnancy (88.1% vs 34.0%; p<0.01). Future diabetes was associated with
      and predicted by HbA1c taken at GDM diagnosis in both South Asian (odds ratio
      4.09, 95% confidence interval 1.35 to 12.40; p<0.05) and Caucasian women (OR
      9.15, 95% CI 1.91 to 43.87; p<0.01) as well as by previously reported risk
      factors of increasing age at follow-up, pregnancy weight, increasing
      hyperglycaemia and insulin requirement during pregnancy. CONCLUSION: GDM
      represents a significant risk factor for future DM development regardless of
      ethnicity. Glycated haemoglobin values at GDM diagnosis have value in predicting
      future diabetes mellitus.

PMID- 17551078
TI  - Sir Henry Halford, president of the Royal College of Physicians, with a note on
      his involvement in the exhumation of King Charles I.
AB  - Henry Halford (formerly Vaughan) (1766-1844) was president of the Royal College
      of Physicians for an unprecedented 24 years. A successful physician, he had to
      resign his post at the Middlesex Hospital because of his growing private
      practice. He was physician to four reigning monarchs and had many famous patients
      including Geogiana Duchess of Devonshire in whom he correctly diagnosed a liver
      abscess when other physicians had failed. He was also involved in the exhumation
      of King Charles I, and the fourth cervical vertebra, through which the King had
      been executed, came into his possession.

PMID- 17551079
TI  - Reflections on retirement.

PMID- 17551080
TI  - Mitochondrial DNA haplogroups and type 2 diabetes: a study of 897 cases and 1010
      controls.
AB  - Mitochondria play a central role in the secretion of insulin by pancreatic beta
      cells, and pathogenic mutations of mitochondrial DNA (mtDNA) can cause diabetes.
      The aetiology of type 2 diabetes has a strong genetic component, raising the
      possibility that genetic variants of mtDNA alter the risk of developing the
      disorder. Recent studies have produced conflicting results. By studying 897 UK
      cases of type 2 diabetes and 1010 population-matched controls, it is shown that
      European mtDNA haplogroups are unlikely to play a major role in the risk of
      developing the disorder.

PMID- 17551081
TI  - Autosomal recessive postlingual hearing loss (DFNB8): compound heterozygosity for
      two novel TMPRSS3 mutations in German siblings.
AB  - Mutations in the transmembrane protease, serine 3 (TMPRSS3) gene, encoding a
      transmembrane serine protease, cause autosomal recessive deafness childhood
      (DFNB8) or congenital onset (DFNB10). TMPRSS3 mutations have been mainly
      identified in patients from Asian and Mediterranean countries and seem to be a
      rare finding in the Northern European population so far. The identification of
      two novel pathogenic TMPRSS3 mutations (c.646C-->T - R216C; c.916G-->A - A306T)
      is described in four affected siblings of German origin with postlingual hearing
      loss, treated by bilateral cochlear implantation with good results. Although
      TMPRSS3 mutations are supposed to be a rare cause of autosomal recessive hearing
      loss, in families with postlingual disease onset TMPRSS3 is the most favourable
      candidate gene after exclusion of GJB2 mutations.

PMID- 17551082
TI  - Phenocopies in families seen by cancer geneticists.

PMID- 17551083
TI  - Pierre Robin sequence may be caused by dysregulation of SOX9 and KCNJ2.
AB  - BACKGROUND: The Pierre Robin sequence (PRS), consisting of cleft palate,
      micrognathia and glossoptosis, can be seen as part of the phenotype in other
      Mendelian syndromes--for instance, campomelic dysplasia (CD) which is caused by
      SOX9 mutations--but the aetiology of non-syndromic PRS has not yet been
      unravelled. OBJECTIVE: To gain more insight into the aetiology of PRS by studying
      patients with PRS using genetic and cytogenetic methods. METHODS: 10 unrelated
      patients with PRS were investigated by chromosome analyses and bacterial
      artificial chromosome arrays. A balanced translocation was found in one patient,
      and the breakpoints were mapped with fluorescence in situ hybridisation and
      Southern blot analysis. All patients were screened for SOX9 and KCNJ2 mutations,
      and in five of the patients expression analysis of SOX9 and KCNJ2 was carried out
      by quantitative real-time PCR. RESULTS: An abnormal balanced karyotype 46,XX,
      t(2;17)(q23.3;q24.3) was identified in one patient with PRS and the 17q
      breakpoint was mapped to 1.13 Mb upstream of the transcription factor SOX9 and
      800 kb downstream of the gene KCNJ2. Furthermore, a significantly reduced SOX9
      and KCNJ2 mRNA expression was observed in patients with PRS. CONCLUSION: Our
      findings suggest that non-syndromic PRS may be caused by both SOX9 and KCNJ2
      dysregulation.

PMID- 17551084
TI  - Different CTNNB1 mutations as molecular genetic proof for the independent origin
      of four Wilms tumours in a patient with a novel germ line WT1 mutation.
AB  - We describe a patient with a novel WT1 pS50X germ line mutation, who developed
      bilateral Wilms tumours, both with stromal-type histology. Both tumours showed
      loss of the wild type WT1 allele (loss of heterozygosity (LOH)) and a tumour
      specific mutation in catenin beta1 (CTNNB1), S45P in the left and Delta45S in the
      right tumour. Molecular analysis of microdissected cells from the left tumour
      revealed the same S45P CTNNB1 mutation in blastema, tubuli, stroma and muscle,
      and a different CTNNB1 mutation (T41A) in stromal cells isolated from another
      area of the same slide. Microdissection of two areas of muscle cells from the
      right tumour revealed the same Delta45S mutation and no CTNNB1 mutation nor LOH
      of WT1 in normal kidney cells. One year later, the patient developed a new set of
      bilateral tumours. Both tumours showed LOH of the wild type WT1 allele, but
      different CTNNB1 mutations as in the first tumours: S45C on the right and S45F on
      the left side, demonstrating that these developed independently and are not
      relapses. This case demonstrates the high risk for the development of Wilms
      tumours in patients with germ line truncation mutations.

PMID- 17551085
TI  - Should healthcare providers have a duty to warn family members of individuals
      with an HNPCC-causing mutation? A survey of patients from the Ontario Familial
      Colon Cancer Registry.
AB  - BACKGROUND: As genetic testing becomes more common and increasingly intertwined
      with medical care, the issues of genetic privacy and doctor-patient
      confidentiality are being examined. Hereditary non-polyposis colorectal cancer
      (HNPCC) is a genetic predisposition to colorectal and certain other cancers.
      Effective screening that can prevent colorectal cancer is an important incentive
      for genetic testing. METHODS: A survey regarding the duty to warn family members
      of the risks associated with an HNPCC-causing mutation was mailed to 227
      participants in the Ontario Familial Colon Cancer Registry (OFCCR). To our
      knowledge, the opinions of patients on this subject have not been reported
      previously in the literature. Responses were analysed quantitatively using the
      SAS system and qualitatively by the review of written comments. RESULTS:
      Completed surveys were returned by 105 participants, with a response rate of
      46.3%. The majority felt a personal responsibility to warn relatives, but there
      was no significant agreement that doctors or genetic counsellors should have a
      duty to warn relatives without a patient's permission. CONCLUSIONS: Patients
      undergoing genetic testing for HNPCC generally understand that relatives could
      benefit from being informed of genetic risk, but may not be willing or able to
      inform each family member. Healthcare professionals should engage patients in a
      discussion of familial implications before genetic testing. An agreement should
      be formulated regarding which of the relatives should be informed. Patients
      should be encouraged to personally disseminate the information, given the
      unrealistic burden on practitioners to perform this task and patients' preference
      for control over the information.

PMID- 17551087
TI  - Impact of the Health Insurance Portability and Accountability Act on participant
      recruitment and retention.
AB  - Recruiting and retaining an adequate sample is critical to the success of any
      research project involving humans. Recent reports indicate that the Health
      Insurance Portability and Accountability Act (HIPAA) privacy rule has adversely
      affected research. Few resources are available to help researchers navigate the
      challenges to recruitment and retention after HIPAA privacy rule implementation.
      This article addresses obstacles to recruitment in prospective clinical research
      studies related to the HIPAA privacy rule, as well as HIPAA-compliant strategies
      to enhance recruitment and retention. Recruitment challenges discussed include
      evolving interpretations of the HIPAA regulations, inability to directly contact
      potential participants, complexity of HIPAA-required documents, increased costs
      of recruitment, and an expanding administrative burden. Among the strategies
      addressed are preparatory research reviews, using clinical collaborators and
      staff liaisons, prescreening potential participants, minimizing participant
      burden during the consent process, enhancing participant follow-up, facilitating
      recruitment for future studies, and streamlining compliance training for staff.

PMID- 17551088
TI  - Effect of an inpatient nurse-directed smoking cessation program.
AB  - The purpose of this study was to evaluate the effect of a nurse-directed smoking
      cessation intervention for adults hospitalized in a small community hospital
      using a quasiexperimental, prospective, longitudinal design with biochemical
      validation of self-reported tobacco abstinence. Sixty-eight inpatients were
      assigned to either a control (n = 30) or an intervention group (n = 38). The
      control group received smoking cessation literature. The intervention group
      received smoking cessation literature and a nursing intervention. Each member of
      the intervention group was randomly assigned to a one or four telephone call
      subgroup for post discharge nurse follow-up at 3 months. Fifty-five participants
      completed the study. Smokers receiving the nurse-directed intervention were
      significantly more likely to be tobacco abstinent at 3 months (n = 17, 55%) than
      smokers in the control group (n = 5, 21%). Within the intervention group, tobacco
      abstinence at 3 months was not significantly different between the one and four
      telephone call groups. For the total sample, smoking relapse was significantly
      higher for participants who lived with another smoker.

PMID- 17551089
TI  - Activity in right temporo-parietal junction is not selective for theory-of-mind.
AB  - Recent researchers have suggested that a region of right temporo-parietal
      junction (RTPJ) selectively subserves the attribution of beliefs to other people
      (Saxe R, Kanwisher N. 2003. People thinking about thinking people: fMRI
      investigations of theory of mind. NeuroImage. 19:1835-1842; Saxe R, Powell LJ.
      2006. It's the thought that counts: specific brain regions for one component of
      theory of mind. Psychol Sci. 17:692-699; Saxe R, Wexler A. 2005. Making sense of
      another mind: the role of the right temporo-parietal junction. Neuropsychologia.
      43:1391-1399). At the same time, a similar RTPJ region has been observed
      repeatedly in a variety of nonsocial tasks that require participants to redirect
      attention to task-relevant stimuli (e.g., Corbetta M, Shulman GL. 2002. Control
      of goal-directed and stimulus-driven attention in the brain. Nat Rev Neurosci.
      3:201-215; Serences JT, Shomstein S, Leber AB, Golay X, Egeth HE, Yantis S. 2005.
      Coordination of voluntary and stimulus-driven attentional control in human
      cortex. Psychol Sci. 16:114-122). However, because these 2 sets of tasks have
      never been compared within the same participants, it remains unclear whether
      these observations refer to the exact same region of RTPJ or may instead involve
      neighboring regions with distinct functional profiles. To test the claim that
      there is a region of RTPJ selective for belief attribution, the current study
      used functional neuroimaging to examine the extent to which cortical loci
      identified by a "theory-of-mind localizer" also distinguish between trials on a
      target detection task that varied demands to reorient attention (i.e., a version
      of the "Posner cueing task"). Results were incompatible with claims of RTPJ
      selectivity for mental state attribution. Regardless of whether regions were
      defined from group analyses or were individually tailored for each participant,
      RTPJ activity was also modulated by the nonsocial attentional task. The overlap
      between theory-of-mind and attentional reorienting suggests the need for new
      accounts of RTPJ function that integrate across these disparate task comparisons.

PMID- 17551090
TI  - The genetic deconstruction of psychosis.
AB  - Psychiatric research, including the search for predisposing genes, has tended to
      proceed under the assumptions that schizophrenia and bipolar disorder, as defined
      in Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, and
      International Statistical Classification of Diseases, 10th Revision, are discrete
      disease entities with distinct etiology and pathogenesis and that these disease
      entities can be identified by current "operational" diagnostic conventions.
      However, recent findings emerging from genetic studies show increasing evidence
      for an overlap in genetic susceptibility across the traditional binary
      classification of psychosis. Moreover, the emerging evidence suggests the
      possibility of relatively specific relationships between genotype and
      psychopathology. For example, variation in Disrupted in Schizophrenia 1 (DISC1)
      and Neuregulin 1 (NRG1) may confer susceptibility to a form of illness with mixed
      features of schizophrenia and mania. The elucidation of genotype-phenotype
      relationships is at an early stage, but current findings highlight the need to
      consider alternative approaches to classification and conceptualization for
      psychiatric research rather than continuing to rely heavily on the traditional
      categorical approach. We can expect that, over the coming years, molecular
      genetics will catalyze a reappraisal of psychiatric nosology as well as
      contribute in a major way to our understanding of pathophysiology and to the
      development of improved treatments. However, our understanding of the brain
      mechanisms that link specific gene actions and products to the subjective
      experience of psychopathological symptoms is likely to be bridged by employing
      intermediate (or endo-) phenotypes in the domains such as cognition,
      neurophysiology, or neuroanatomy rather than relying upon clinical measures
      alone.

PMID- 17551091
TI  - Design and evaluation of small interfering RNAs that target expression of the N
      methyl-D-aspartate receptor NR1 subunit gene in the spinal cord dorsal horn.
AB  - NR1 is an essential subunit of the N-methyl-D-aspartate (NMDA) receptor, which at
      the spinal level is involved in injury-induced pain hypersensitivity and morphine
      tolerance. An in vitro luciferase assay was used to identify candidate and
      control (inactive) short interfering RNA (siRNA) sequences that are expressed by
      a recombinant adeno-associated virus (rAAV) plasmid. rAAV vectors targeting the
      NR1 subunit were prepared that express active or control (mismatch) siRNA
      sequences and injected into the mouse spinal cord dorsal horn (SCDH). Three weeks
      after vector administration, green fluorescent protein labeling of the
      ipsilateral SCDH confirmed the spatial localization of the viral transduction.
      Active siRNAs resulted in a 60 to 75% knockdown of NR1 mRNA and protein in the
      area of the virus injection. The spatial knockdown persisted for at least 6
      months after a single administration of the vector. Neither the active nor the
      mismatch siRNAs resulted in cellular toxicity as measured by nuclear staining and
      cell integrity. The vector-derived knockdown of NR1 expression in SCDH did not
      alter acute thermal or mechanical stimulus paw-withdrawal thresholds. However,
      the vector-derived siRNA prevented the mechanical allodynia measured at 24 and 48
      h after injection into the paw of the inflammatory agent, Complete Freund's
      adjuvant. These results demonstrate that vector-derived siRNAs can be used to
      produce an in vivo spatial knockdown of the expression and function of the NMDA
      receptor that is confined to the ipsilateral SCDH. Vector-derived siRNAs may have
      therapeutic potential for the management of injury-induced pain resulting from
      the activation of NMDA receptors in the SCDH.

PMID- 17551092
TI  - Nitrotyrosylation of Ca2+ channels prevents c-Src kinase regulation of colonic
      smooth muscle contractility in experimental colitis.
AB  - Basal levels of c-Src kinase are known to regulate smooth muscle Ca(2+) channels.
      Colonic inflammation results in attenuated Ca(2+) currents and muscle
      contraction. Here, we examined the regulation of calcium influx-dependent
      contractility by c-Src kinase in experimental colitis. Ca(2+)-influx induced
      contractions were measured by isometric tension recordings of mouse colonic
      longitudinal muscle strips depolarized by high K(+). The E(max) to CaCl(2) was
      significantly less in inflamed tissues (38.4 +/- 7.6%) than controls, indicative
      of reduced Ca(2+) influx. PP2 [4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4
      d]pyrimidine], a selective Src kinase inhibitor, significantly reduced the
      contractile amplitude and shifted the pD(2) from 3.88 to 2.44 in controls,
      whereas it was ineffective in inflamed tissues (3.66 versus 3.43). After
      pretreatment with a SIN-1 (3-morpholinosydnonimine)/peroxynitrite combination,
      the maximal contraction to CaCl(2) was reduced by 46 +/- 7% in controls but
      unaffected in inflamed tissues (13 +/- 11%). Peroxynitrite also prevented the
      inhibitory effect of PP2 in control tissues. In colonic single smooth muscle
      cells, PP2 inhibited Ca(2+) currents by 84.1 +/- 3.9% in normal but only 36.2 +/-
      13% in inflamed tissues. Neither the Ca(2+) channel Ca(v)1.2b, gene expression,
      nor the c-Src kinase activity was altered by inflammation. Western blot analysis
      showed no change in the Ca(2+) channel protein expression but increased
      nitrotyrosylated-Ca(2+) channel proteins during inflammation. These data suggest
      that post-translational modification of Ca(2+) channels during inflammation,
      possibly nitrotyrosylation, prevents c-Src kinase regulation resulting in
      decreased Ca(2+) influx.

PMID- 17551093
TI  - Agmatine induces antihyperalgesic effects in diabetic rats and a superadditive
      interaction with R(-)-3-(2-carboxypiperazine-4-yl)-propyl-1-phosphonic acid, a N
      methyl-D-aspartate-receptor antagonist.
AB  - Agmatine, an endogenous cationic amine resulting from the decarboxylation of L
      arginine, produces antihyperalgesic and antiallodynic effects in animal models of
      chronic neuropathic and inflammatory pain. We examined the effect of agmatine on
      tactile and thermal allodynia and on mechanical hyperalgesia in streptozocin
      induced diabetic rats. To determine its mechanism of action and the potential
      interest of some of its combinations, the antihyperalgesic effect of agmatine was
      challenged with alpha(2)-adrenergic imidazoline and opioid-receptor antagonists,
      and its interaction with the opioid-receptor agonist morphine, the competitive N
      methyl-D-aspartate receptor antagonist D-CPP [R(-)-3-(2-carboxypiperazine-4-yl)
      propyl-1-phosphonic acid], and the nitric-oxide synthase inhibitor L-NAME (L-N(G)
      nitro-L-arginine methyl ester) were examined. When intrathecally (i.t.) injected
      (4.4 to 438 nmol/rat), agmatine was ineffective in normal rats but suppressed
      tactile allodynia (von Frey hair test), thermal allodynia (tail immersion test),
      and mechanical hyperalgesia (paw-pressure test) in diabetic rats. This spinal
      antihyperalgesic effect was suppressed by idazoxan (40 micromol/rat i.t.) but not
      by yohimbine (40 micromol/rat i.t.) or naloxone (0.69 micromol/rat i.v.). In
      diabetic rats, an isobolographic analysis showed that combinations of i.t.
      agmatine with i.v. L-NAME or with i.t. morphine resulted in an additive
      antihyperalgesic effect, whereas the agmatine/D-CPP i.t. combination was
      superadditive. In summary, the present findings reveal that spinal agmatine
      produces antiallodynic and antihyperalgesic effects in diabetic neuropathic pain
      involving, at least for its antihyperalgesic effect, the imidazoline receptors.
      Moreover, agmatine combined with D-CPP produces an antinociceptive synergy in
      experimental neuropathy, opening opportunities in the development of new
      strategies for pain therapy.

PMID- 17551094
TI  - A novel natural compound, a cycloanthranilylproline derivative (Fuligocandin B),
      sensitizes leukemia cells to apoptosis induced by tumor necrosis factor related
      apoptosis-inducing ligand (TRAIL) through 15-deoxy-Delta 12, 14 prostaglandin J2
      production.
AB  - Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) induces
      apoptosis in many transformed cells; however, not all human tumors respond to
      TRAIL, potentially limiting its therapeutic utility. Although there is
      substantial evidence that cytotoxic drugs can augment sensitivity to TRAIL, it
      has become important to know what kinds of nontoxic drugs can be used together
      with TRAIL. We thus screened several natural compounds that can overcome
      resistance to TRAIL and found that a cycloanthranilylproline derivative,
      Fuligocandin B (FCB), an extract of myxomycete Fuligo candida, exhibited
      significant synergism with TRAIL. Treatment of the TRAIL-resistant cell line KOB
      with FCB and TRAIL resulted in apparent apoptosis, which was not induced by
      either agent alone. FCB increased the production of 15-deoxy-Delta(12,14)
      prostaglandin J(2) (15d-PGJ(2)), an endogenous PPAR gamma ligand, through
      activation of cyclooxygenase-2 (COX-2). This unique mechanism highlighted the
      fact that 15d-PGJ(2) directly enhanced sensitivity to TRAIL by inhibiting
      multiple antiapoptotic factors. More importantly, similar effects were observed
      in other leukemia cell lines irrespective of their origin. The enhancement was
      observed regardless of PPAR gamma expression and was not blocked even by
      peroxisome proliferator-activated receptor-gamma (PPAR gamma) siRNA. These
      results indicate that 15d-PGJ(2) sensitizes TRAIL-resistant cells to TRAIL in a
      PPAR gamma-independent manner and that the use of 15d-PGJ(2) or its inducers,
      such as FCB, is a new strategy for cancer therapy.

PMID- 17551095
TI  - Cytotoxic T lymphocytes carrying a pattern recognition protein Tag7 can detect
      evasive, HLA-negative but Hsp70-exposing tumor cells, thereby ensuring FasL/Fas
      mediated contact killing.
AB  - Within the broad problem of host immune surveillance versus tumor immune evasion,
      a most intriguing question is how the cellular immunity can cope with cancerous
      cells that have gotten rid of the classical antigen-presenting machinery. One
      such option stems from (1) the fact that HLA loss is often attended with
      expression of Hsp70 on the tumor cell surface, and (2) our findings that human
      lymphocytes express a protein Tag7 (also known as PGRP-S) capable of tight and
      specific interaction with cognate Hsp70. Here we show that a subpopulation of
      human CD4(+)CD25(+) lymphocytes, obtained either in culture as lymphokine
      activated killers or directly from healthy donors, carry Tag7 and FasL on their
      surface and can indeed kill the HLA-negative tumor-derived cells K562 and MOLT-4
      that expose Hsp70 and Fas. The primary binding of lymphocyte Tag7 to target-cell
      Hsp70 is very specific (eg, it is blocked by preincubating either cell with
      minimal peptides from the "partner" protein), and secures cell contact
      indispensable for subsequent FasL/Fas-triggered apoptosis. Unrelated to natural
      killer cell action or the putative role of Hsp as an antigen-presenting
      substitute, this novel mechanism is rather a backup analog of orthodox (CD8(+))
      target recognition (Tag7 acting as built-in T-cell receptor and Hsp70 itself as
      ligand).

PMID- 17551096
TI  - Eye-blink conditioning is associated with changes in synaptic ultrastructure in
      the rabbit interpositus nuclei.
AB  - Eye-blink conditioning involves the pairing of a conditioned stimulus (usually a
      tone) to an unconditioned stimulus (air puff), and it is well established that an
      intact cerebellum and interpositus nucleus, in particular, are required for this
      form of classical conditioning. Changes in synaptic number or structure have long
      been proposed as a mechanism that may underlie learning and memory, but
      localizing these changes has been difficult. Thus, the current experiment took
      advantage of the large amount of research conducted on the neural circuitry that
      supports eye-blink conditioning by examining synaptic changes in the rabbit
      interpositus nucleus. Synaptic quantifications included total number of synapses
      per neuron, numbers of excitatory versus inhibitory synapses, synaptic curvature,
      synaptic perforations, and the maximum length of the synapses. No overall changes
      in synaptic number, shape, or perforations were observed. There was, however, a
      significant increase in the length of excitatory synapses in the conditioned
      animals. This increase in synaptic length was particularly evident in the concave
      shaped synapses. These results, together with previous findings, begin to
      describe a sequence of synaptic change in the interpositus nuclei following eye
      blink conditioning that would appear to begin with structural change and end with
      an increase in synaptic number.

PMID- 17551097
TI  - Metaplastic effect of apamin on LTP and paired-pulse facilitation.
AB  - In area CA1 of hippocampal slices, a single 1-sec train of 100-Hz stimulation
      generally triggers a short-lasting long-term potentiation (S-LTP) of 1-2 h. Here,
      we found that when such a train was applied 45 min after application of the small
      conductance Ca(2+)-activated K(+ )(SK) channel blocker apamin, it induced a long
      lasting LTP (L-LTP) of several hours, instead of an S-LTP. Apamin-induced SK
      channel blockage is known to resist washing. Nevertheless, the aforementioned
      effect is not a mere delayed effect; it is metaplastic. Indeed, when a single
      train was delivered to the Schaffer's collaterals during apamin application, it
      induced an S-LTP, like in the control situation. At the moment of this LTP
      induction (15th min of apamin application), the SK channel blockage was
      nevertheless complete. Indeed, at that time, under the influence of apamin, the
      amplitude of the series of field excitatory postsynaptic potentials (fEPSPs)
      triggered by a stimulation train was increased. We found that the metaplastic
      effect of apamin on LTP was crucially dependent on the NO-synthase pathway,
      whereas the efficacy of the NMDA receptors was not modified at the time of its
      occurrence. We also found that apamin produced an increase in paired-pulse
      facilitation not during, but after, the application of the drug. Finally, we
      found that the induction of each of these two metaplastic phenomena was mediated
      by NMDA receptors. A speculative unitary hypothesis to explain these phenomena is
      proposed.

PMID- 17551098
TI  - Heme oxygenase-1, carbon monoxide, and bilirubin induce tolerance in recipients
      toward islet allografts by modulating T regulatory cells.
AB  - Heme oxygenase-1 (HO-1) induction in, or carbon monoxide (CO), or bilirubin
      administration to, donors and/or recipients frequently lead to long-term survival
      (>100 days) of DBA/2 islets into B6AF1 recipients. We tested here whether similar
      treatments show value in a stronger immunogenetic combination, i.e., BALB/c to
      C57BL/6, and attempted to elucidate the mechanism accounting for tolerance.
      Induction of HO-1, administering CO or bilirubin to the donor, the islets or the
      recipient, prolonged islet allograft survival to different extents. Combining all
      the above treatments (the "combined" protocol) led to survival for >100 days and
      antigen-specific tolerance to 60% of the transplanted grafts. A high level of
      forkhead box P3 (Foxp3) and transforming growth factor beta (TGF-beta) expression
      was detected in the long-term surviving grafts. With the combined protocol,
      significantly more T regulatory cells (Tregs) were observed surrounding islets 7
      days following transplantation. No prolongation of graft survival was observed
      using the combined protocol when CD4+ CD25+ T cells were predepleted from the
      recipients before transplantation. In conclusion, our combined protocol led to
      long-term survival and tolerance to islets in the BALB/c to C57BL/6 combination
      by promoting Foxp3+ Tregs; these cells played a critical role in the induction
      and maintenance of tolerance in the recipient.

PMID- 17551099
TI  - Diet-induced hypermethylation at agouti viable yellow is not inherited
      transgenerationally through the female.
AB  - The effects of nonmutagenic environmental exposures can sometimes be transmitted
      for several generations, suggesting transgenerational inheritance of induced
      epigenetic variation. Methyl donor supplementation of female mice during
      pregnancy induces CpG hypermethylation at the agouti viable yellow (A(vy)) allele
      in A(vy)/a offspring. Epigenetic inheritance occurs at A(vy); when passed through
      the female germ line, A(vy) epigenotype is not completely "reset." We therefore
      tested whether diet-induced epigenetic alterations at A(vy) are inherited
      transgenerationally. Female A(vy)/a mice were weaned onto either control (n=6) or
      a methyl-supplemented diet (n=5). These F0 dams were mated with a/a males. All F1
      and F2 A(vy)/a females were weaned onto the same diet as their mothers, then
      mated with a/a males. F1, F2, and F3 A(vy)/a offspring were classified for coat
      color, an indicator of A(vy) methylation. In total, 62 F1, 98 F2, and 209 F3
      A(vy)/a mice were studied. As expected, average A(vy)/a coat color was darker in
      the supplemented group (P<0.01). However, there was no cumulative effect of
      supplementation across successive generations. These results suggest that, in the
      female germ line, diet-induced A(vy) hypermethylation occurs in the absence of
      additional epigenetic modifications that normally confer transgenerational
      epigenetic inheritance at the locus.

PMID- 17551100
TI  - Identification of polymorphisms in the human 11beta-hydroxysteroid dehydrogenase
      type 2 gene promoter: functional characterization and relevance for salt
      sensitivity.
AB  - Reduced activity of 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2)
      plays a role in essential hypertension and the sensitivity of blood pressure to
      dietary salt. Nonconservative mutations in the coding region are extremely rare
      and do not explain the variable 11beta-HSD2 activity. We focused therefore on the
      5'-regulatory region and identified and characterized the first promoter
      polymorphisms. Transfections of variants G-209A and G-126A into SW620 cells
      reduced promoter activity and affinity for activators nuclear factor 1 (NF1) and
      Sp1. Chromatin immunoprecipitation revealed Sp1, NF1, and glucocorticoid receptor
      (GR) binding to the HSD11B2 promoter. Dexamethasone induced expression of mRNA
      and activity of HSD11B2. GR and/or NF1 overexpression increased endogenous
      HSD11B2 mRNA and activity. GR complexes cooperated with NF1 to activate HSD11B2,
      an effect diminished in the presence of the G-209A variant. When compared to salt
      resistant subjects (96), salt-sensitive volunteers (54) more frequently had the G
      209A variant, higher occurrence of alleles A4/A7 of polymorphic microsatellite
      marker, and higher urinary ratios of cortisol to cortisone metabolites. First, we
      conclude that the mechanism of glucocorticoid-induced HSD11B2 expression is
      mainly mediated by cooperation between GR and NF1 on the HSD11B2 promoter and,
      second, that the newly identified promoter variants reduce activity and
      cooperation of cognate transcription factors, resulting in diminished HSD11B2
      transcription, an effect favoring salt sensitivity.

PMID- 17551101
TI  - Vitamin D receptor signaling contributes to susceptibility to infection with
      Leishmania major.
AB  - We have previously reported that 1alpha,25-dihydroxyvitamin D3 (1alpha,25(OH)2D3)
      can selectively suppress key functions of interferon-gamma (IFN-gamma) activated
      macrophages. To further explore this mechanism for its relevance in vivo, we
      investigated an infection model that crucially depends on the function of IFN
      gamma activated macrophages, the infection with the intracellular protozoan
      Leishmania major. 1Alpha,25(OH)2D3 treatment of L. major infected macrophages
      demonstrated a vitamin D receptor (Vdr) dependent inhibition of macrophage
      killing activity. Further analysis showed that this was a result of decreased
      production of nitric oxide by 1alpha,25(OH)2D3-treated macrophages due to Vdr
      dependent up-regulation of arginase 1 expression, which overrides NO production
      by Nos2. When analyzing the course of infection in vivo, we found that Vdr
      knockout (Vdr-KO) mice were more resistant to L. major infection than their wild
      type littermates. This result is in agreement with an inhibitory influence of
      1alpha,25(OH)2D3 on the macrophage mediated host defense. Further investigation
      showed that Vdr-KO mice developed an unaltered T helper cell type 1 (Th1)
      response on infection as indicated by normal production of IFN-gamma by CD4+ and
      CD8+ T cells. Therefore, we propose that the absence of 1alpha,25(OH)2D3-mediated
      inhibition of macrophage microbicidal activity in Vdr-KO mice results in
      increased resistance to Leishmania infection.

PMID- 17551102
TI  - Comments on point:counterpoint: "the lactate paradox does/does not occur during
      exercise at high altitude".

PMID- 17551103
TI  - Matrix metalloproteinase-1 therapy improves muscle healing.
AB  - Muscle undergoes time-dependent phases of healing after injury, which ultimately
      results in residual fibrosis in the injured area. The use of exogenous matrix
      metalloproteinases (MMPs) may improve recovery after muscle injury by promoting
      the digestion of existing fibrous tissue and releasing local growth factors. In
      the current experiment, bilateral gastrocnemius (GM) lacerations were created in
      severe combined immunodeficient mice. Twenty-five days after injury (peak
      posttraumatic fibrosis), C2C12 cells (myoblasts) transduced with the LacZ
      reporter gene were injected with exogenous MMP-1 into the right GMs at the site
      of injury; the cells were also injected along with PBS (control) at the site of
      injury in the left GMs. The muscle tissues were examined histologically via X
      gal, hemotoxylin and eosin, and Masson's trichrome staining. The MMP-treated
      limbs contained more regenerating myofibers than did the control limbs (MMP 170+/
      96 fibers, control 62+/-51 fibers; P<0.001). Less fibrous tissue was observed
      within MMP-treated muscles (MMP: 24+/-11%, control: 35+/-15%; P<0.01). These
      results suggest that the direct injection of MMP-1 into the zone of injury during
      fibrosis can enhance muscle regeneration by increasing the number of myofibers
      and decreasing the amount of fibrous tissue.

PMID- 17551104
TI  - Counterpoint: the lactate paradox does not occur during exercise at high
      altitude.

PMID- 17551105
TI  - Comments on point:counterpoint: "the lactate paradox does/does not occur during
      exercise at high altitude".

PMID- 17551106
TI  - Comments on point:counterpoint: "the lactate paradox does/does not occur during
      exercise at high altitude".

PMID- 17551107
TI  - Comments on point:counterpoint: "the lactate paradox does/does not occur during
      exercise at high altitude".

PMID- 17551108
TI  - Comment on point:counterpoint: "cardiovascular variability is/is not an index of
      autonomic control of circulation".

PMID- 17551109
TI  - Comments on point:counterpoint: "the lactate paradox does/does not occur during
      exercise at high altitude".

PMID- 17551110
TI  - Comments on point:counterpoint: "the lactate paradox does/does not occur during
      exercise at high altitude".

PMID- 17551111
TI  - Commentary on "restrained whole body plethysmography for measure of strain
      specific and allergen-induced airway responsiveness in conscious mice".

PMID- 17551113
TI  - Maintenance of end-expiratory recruitment with increased respiratory rate after
      saline-lavage lung injury.

PMID- 17551115
TI  - Comments on "experimental determination of net protein charge, [A]tot, and Ka of
      nonvolatile buffers in bird plasma".

PMID- 17551116
TI  - Comments on point:counterpoint: "the lactate paradox does/does not occur during
      exercise at high altitude".

PMID- 17551117
TI  - The cover . Paeonia suffruticosa.

PMID- 17551118
TI  - A piece of my mind. The sounds of silence.

PMID- 17551119
TI  - Campus tragedy prompts closer look at mental health of college students.

PMID- 17551120
TI  - Report quantifies diabetes complications.

PMID- 17551121
TI  - Face masks, respirators might help during pandemic flu outbreak.

PMID- 17551126
TI  - Priorities to improve health outcomes.

PMID- 17551127
TI  - Genomics and public health research.

PMID- 17551128
TI  - Prognostic value of HIV-1 RNA, CD4 cell count, and CD4 Cell count slope for
      progression to AIDS and death in untreated HIV-1 infection.

PMID- 17551129
TI  - Folic acid for the prevention of colorectal adenomas: a randomized clinical
      trial.
AB  - CONTEXT: Laboratory and epidemiological data suggest that folic acid may have an
      antineoplastic effect in the large intestine. OBJECTIVE: To assess the safety and
      efficacy of folic acid supplementation for preventing colorectal adenomas.
      DESIGN, SETTING, AND PARTICIPANTS: A double-blind, placebo-controlled, 2-factor,
      phase 3, randomized clinical trial conducted at 9 clinical centers between July
      6, 1994, and October 1, 2004. Participants included 1021 men and women with a
      recent history of colorectal adenomas and no previous invasive large intestine
      carcinoma. INTERVENTION: Participants were randomly assigned in a 1:1 ratio to
      receive 1 mg/d of folic acid (n = 516) or placebo (n = 505), and were separately
      randomized to receive aspirin (81 or 325 mg/d) or placebo. Follow-up consisted of
      2 colonoscopic surveillance cycles (the first interval was at 3 years and the
      second at 3 or 5 years later). MAIN OUTCOME MEASURES: The primary outcome measure
      was occurrence of at least 1 colorectal adenoma. Secondary outcomes were the
      occurrence of advanced lesions (> or =25% villous features, high-grade dysplasia,
      size > or =1 cm, or invasive cancer) and adenoma multiplicity (0, 1-2, or > or =3
      adenomas). RESULTS: During the first 3 years, 987 participants (96.7%) underwent
      colonoscopic follow-up, and the incidence of at least 1 colorectal adenoma was
      44.1% for folic acid (n = 221) and 42.4% for placebo (n = 206) (unadjusted risk
      ratio [RR], 1.04; 95% confidence interval [CI], 0.90-1.20; P = .58). Incidence of
      at least 1 advanced lesion was 11.4% for folic acid (n = 57) and 8.6% for placebo
      (n = 42) (unadjusted RR, 1.32; 95% CI, 0.90-1.92; P = .15). A total of 607
      participants (59.5%) underwent a second follow-up, and the incidence of at least
      1 colorectal adenoma was 41.9% for folic acid (n = 127) and 37.2% for placebo (n
      = 113) (unadjusted RR, 1.13; 95% CI, 0.93-1.37; P = .23); and incidence of at
      least 1 advanced lesion was 11.6% for folic acid (n = 35) and 6.9% for placebo (n
      = 21) (unadjusted RR, 1.67; 95% CI, 1.00-2.80; P = .05). Folic acid was
      associated with higher risks of having 3 or more adenomas and of noncolorectal
      cancers. There was no significant effect modification by sex, age, smoking,
      alcohol use, body mass index, baseline plasma folate, or aspirin allocation.
      CONCLUSIONS: Folic acid at 1 mg/d does not reduce colorectal adenoma risk.
      Further research is needed to investigate the possibility that folic acid
      supplementation might increase the risk of colorectal neoplasia. TRIAL
      REGISTRATION: clinicaltrials.gov Identifier: NCT00272324.

PMID- 17551130
TI  - Pay for performance, quality of care, and outcomes in acute myocardial
      infarction.
AB  - CONTEXT: Pay for performance has been promoted as a tool for improving quality of
      care. In 2003, the Centers for Medicare & Medicaid Services (CMS) launched the
      largest pay-for-performance pilot project to date in the United States, including
      indicators for acute myocardial infarction. OBJECTIVE: To determine if pay for
      performance was associated with either improved processes of care and outcomes or
      unintended consequences for acute myocardial infarction at hospitals
      participating in the CMS pilot project. DESIGN, SETTING, AND PARTICIPANTS: An
      observational, patient-level analysis of 105,383 patients with acute non-ST
      segment elevation myocardial infarction enrolled in the Can Rapid Risk
      Stratification of Unstable Angina Patients Suppress Adverse Outcomes With Early
      Implementation of the American College of Cardiology/American Heart Association
      (ACC/AHA) Guidelines (CRUSADE) national quality-improvement initiative. Patients
      were treated between July 1, 2003, and June 30, 2006, at 54 hospitals in the CMS
      program and 446 control hospitals. MAIN OUTCOME MEASURES: The differences in the
      use of ACC/AHA class I guideline recommended therapies and in-hospital mortality
      between pay for performance and control hospitals. RESULTS: Among treatments
      subject to financial incentives, there was a slightly higher rate of improvement
      for 2 of 6 targeted therapies at pay-for-performance vs control hospitals (odds
      ratio [OR] comparing adherence scores from 2003 through 2006 at half-year
      intervals for aspirin at discharge, 1.31; 95% confidence interval [CI], 1.18-1.46
      vs OR, 1.17; 95% CI, 1.12-1.21; P = .04) and for smoking cessation counseling
      (OR, 1.50; 95% CI, 1.29-1.73 vs OR, 1.28; 95% CI, 1.22-1.35; P = .05). There was
      no significant difference in a composite measure of the 6 CMS rewarded therapies
      between the 2 hospital groups (change in odds per half-year period of receiving
      CMS therapies: OR, 1.23; 95% CI, 1.15-1.30 vs OR, 1.17; 95% CI, 1.14-1.20; P =
      .16). For composite measures of acute myocardial infarction treatments not
      subject to incentives, rates of improvement were not significantly different (OR,
      1.09; 95% CI, 1.05-1.14 vs OR, 1.08; 95% CI, 1.06-1.09; P = .49). Overall, there
      was no evidence that improvements in in-hospital mortality were incrementally
      greater at pay-for-performance sites (change in odds of in-hospital death per
      half-year period, 0.91; 95% CI, 0.84-0.99 vs 0.97; 95% CI, 0.94-0.99; P = .21).
      CONCLUSIONS: Among hospitals participating in a voluntary quality-improvement
      initiative, the pay-for-performance program was not associated with a significant
      incremental improvement in quality of care or outcomes for acute myocardial
      infarction. Conversely, we did not find evidence that pay for performance had an
      adverse association with improvement in processes of care that were not subject
      to financial incentives. Additional studies of pay for performance are needed to
      determine its optimal role in quality-improvement initiatives.

PMID- 17551131
TI  - Rectal administration of artemisinin derivatives for the treatment of malaria.
AB  - CONTEXT: Rectal administration of artemisinin derivatives is a potentially
      lifesaving emergency treatment of severe malaria. Many different preparations are
      marketed in tropical countries, but their pharmacokinetic disposition and
      clinical efficacy may vary. OBJECTIVE: To review the pharmacokinetics, efficacy,
      and safety of rectally administered artesunate, artemisinin, dihydroartemisinin,
      and artemether. DATA SOURCES: We searched the MEDLINE, EMBASE, Cochrane Database
      of Clinical Reviews, Global Health, Web of Science, and CINAHL computerized
      databases up to December 2006, along with reviewing unpublished data from
      conference proceedings, pharmaceutical companies, and regulatory applications.
      Studies in languages other than English were translated. STUDY SELECTION: Studies
      were included involving rectal administration of an artemisinin derivative to
      healthy volunteers or patients with measurement of plasma drug concentrations or
      rates of initial parasite clearance. Both single-arm and comparative trials were
      included. DATA EXTRACTION: Forty-five studies were identified, of which 39
      eligible studies were included in the review. Primary efficacy outcome measures
      included parasite density as a percentage of baseline at 12 and 24 hours
      following the first dose. Pharmacokinetic variables included maximum plasma
      concentration (C(max)), time to C(max) (T(max)), and area under the plasma
      concentration-time curve. Weighted means were calculated from available data.
      DATA SYNTHESIS: Thirty-two studies provided valid clinical efficacy data: 19 of
      artesunate, 10 of artemisinin, 2 of dihydroartemisinin, and 1 of artemether. All
      demonstrated prompt parasite clearance, with evidence of a dose-dependent effect
      for artesunate. Mortality rates in severe malaria (weighted means, 0%-13%) were
      consistent with those expected. Eight studies compared rectal artemisinin with
      conventional parenteral treatment (quinine, artemether, or artesunate) for severe
      malaria. Despite similar clinical outcomes, rectal artemisinin derivatives
      initiated parasite clearance more rapidly than parenteral treatment (percentage
      of baseline at 12 hours, < or =27% vs > or =56%, respectively). Eighteen
      pharmacokinetic studies were identified, including 13 of artesunate. There was
      marked interindividual variability in most pharmacokinetic variables, but
      artesunate achieved an earlier T(max) and higher C(max) and area under the plasma
      concentration-time curve than other artemisinin derivatives. CONCLUSIONS:
      Available rectal preparations of artemisinin derivatives differ in their
      pharmacokinetic disposition. Most available evidence pertains to artesunate and
      artemisinin. Despite marked interindividual variability in bioavailability,
      rectal preparations appear to have acceptable therapeutic efficacy, including in
      severe illness.

PMID- 17551132
TI  - Does this patient have dementia?
AB  - CONTEXT: While as many as 5 million individuals in the United States have
      dementia, many others have memory complaints. Brief tests to screen for cognitive
      impairment could help guide dementia diagnosis. OBJECTIVE: To review the
      literature concerning the practicality and accuracy of brief cognitive screening
      instruments in primary care. DATA SOURCES: A search of MEDLINE (including data
      from AIDSLINE, BioethicsLine, and HealthSTAR) and psycINFO was conducted from
      January 2000 through April 2006 to update previous reviews. STUDY SELECTION:
      Studies of patients aged 60 years and older and use of an acceptable criterion
      standard to diagnose dementia were considered. DATA EXTRACTION: Studies were
      assessed by 2 independent reviewers for eligibility and quality. A third
      independent reviewer adjudicated disagreements. Data for likelihood ratios (LRs)
      were extracted. DATA SYNTHESIS: Twenty-nine studies using 25 different screening
      instruments met inclusion criteria; some studies evaluated several different
      instruments, thus, information could be examined for 38 unique instrument/study
      combinations. RESULTS: For the commonly used Mini-Mental State Examination, the
      median LR for a positive result was 6.3 (95% confidence interval [CI], 3.4-47.0)
      and the median LR for a negative result was 0.19 (95%CI, 0.06-0.37). Briefer
      approaches are available but have not been studied as frequently. Reports from an
      informant that the patient has memory loss yields an LR of 6.5 (95% CI, 4.4-9.6)
      for dementia. The Memory Impairment Screen takes 4 minutes to ask 4 items and has
      an LR for a positive result of 33 (95% CI, 15.0-72.0) and an LR for a negative
      result is 0.08 (95% CI, 0.02-0.3). Clock drawings are helpful in 1- to 3-minute
      forms, but must be scored appropriately and sensitivity to mild forms of
      impairment can be low. CONCLUSIONS: Clinicians should select 1 primary tool based
      on (1) the population receiving care; (2) an awareness of the effects of
      educational level, race, and age on scoring; and (3) consideration of adding 1 or
      2 other tools for special situations as needed.

PMID- 17551133
TI  - Testing pesticides in humans: of mice and men divided by ten.

PMID- 17551134
TI  - Folate and cancer--timing is everything.

PMID- 17551135
TI  - JAMA patient page. Dementia.

PMID- 17551136
TI  - Serum proteomic classifier for predicting response to epidermal growth factor
      receptor inhibitor therapy: have we built a better mousetrap?

PMID- 17551137
TI  - Cisplatin versus carboplatin for patients with metastatic non-small-cell lung
      cancer--an old rivalry renewed.

PMID- 17551138
TI  - Cooperative groups say NCI trials funding inadequate; some turn to industry.

PMID- 17551139
TI  - European Union creates its own "critical path".

PMID- 17551140
TI  - Stat bite: State epidemiologists by specialty.

PMID- 17551141
TI  - Epidemiologists in short supply, states say.

PMID- 17551142
TI  - Environmental chemicals--not just overeating--may cause obesity.

PMID- 17551143
TI  - Preliminary breast cancer vaccine study shows promise.

PMID- 17551144
TI  - Mass spectrometry to classify non-small-cell lung cancer patients for clinical
      outcome after treatment with epidermal growth factor receptor tyrosine kinase
      inhibitors: a multicohort cross-institutional study.
AB  - BACKGROUND: Some but not all patients with non-small-cell lung cancer (NSCLC)
      respond to treatment with epidermal growth factor receptor (EGFR) tyrosine kinase
      inhibitors (TKIs). We developed and tested the ability of a predictive algorithm
      based on matrix-assisted laser desorption ionization (MALDI) mass spectrometry
      (MS) analysis of pretreatment serum to identify patients who are likely to
      benefit from treatment with EGFR TKIs. METHODS: Serum collected from NSCLC
      patients before treatment with gefitinib or erlotinib were analyzed by MALDI MS.
      Spectra were acquired independently at two institutions. An algorithm to predict
      outcomes after treatment with EGFR TKIs was developed from a training set of 139
      patients from three cohorts. The algorithm was then tested in two independent
      validation cohorts of 67 and 96 patients who were treated with gefitinib and
      erlotinib, respectively, and in three control cohorts of patients who were not
      treated with EGFR TKIs. The clinical outcomes of survival and time to progression
      were analyzed. RESULTS: An algorithm based on eight distinct m/z features was
      developed based on outcomes after EGFR TKI therapy in training set patients.
      Classifications based on spectra acquired at the two institutions had a
      concordance of 97.1%. For both validation cohorts, the classifier identified
      patients who showed improved outcomes after EGFR TKI treatment. In one cohort,
      median survival of patients in the predicted "good" and "poor" groups was 207 and
      92 days, respectively (hazard ratio [HR] of death in the good versus poor groups
      = 0.50, 95% confidence interval [CI] = 0.24 to 0.78). In the other cohort, median
      survivals were 306 versus 107 days (HR = 0.41, 95% CI = 0.17 to 0.63). The
      classifier did not predict outcomes in patients who did not receive EGFR TKI
      treatment. CONCLUSION: This MALDI MS algorithm was not merely prognostic but
      could classify NSCLC patients for good or poor outcomes after treatment with EGFR
      TKIs. This algorithm may thus assist in the pretreatment selection of appropriate
      subgroups of NSCLC patients for treatment with EGFR TKIs.

PMID- 17551145
TI  - Cisplatin- versus carboplatin-based chemotherapy in first-line treatment of
      advanced non-small-cell lung cancer: an individual patient data meta-analysis.
AB  - BACKGROUND: Because the efficacy of carboplatin and cisplatin in the treatment of
      advanced non-small-cell lung cancer (NSCLC) has not been proven to be equivalent,
      an individual patient data meta-analysis comparing the two treatments was
      performed. METHODS: Randomized trials comparing carboplatin to cisplatin in first
      line treatment of advanced NSCLC were identified and their electronic databases
      obtained. A general variance-based method was used to estimate the summary hazard
      ratios (HRs), odds ratios (ORs), and their 95% confidence intervals (CIs) for
      mortality, objective response, and toxicity. Cochran's chi-square test (Q test)
      was used to test for heterogeneity among trials, and the I2 index, which
      expresses the proportion of variability of the results due to heterogeneity, was
      calculated. A random-effects model that takes into account interstudy variation
      was also applied. All statistical tests were two-sided. RESULTS: Nine trials that
      included a total of 2968 patients were analyzed; overall median follow-up was
      1021 days. The objective response rate was higher for patients treated with
      cisplatin than for patients treated with carboplatin (30% versus 24%,
      respectively; OR = 1.37; 95% CI = 1.16 to 1.61; P<.001). Carboplatin treatment
      was associated with a non-statistically significant increase in the hazard of
      mortality relative to treatment with cisplatin (HR = 1.07; 95% CI = 0.99 to 1.15;
      P = .100). In patients with nonsquamous tumors and those treated with third
      generation chemotherapy, carboplatin-based chemotherapy was associated with a
      statistically significant increase in mortality (HR = 1.12; 95% CI = 1.01 to 1.23
      and HR = 1.11; 95% CI = 1.01 to 1.21, respectively). Cisplatin-based chemotherapy
      was associated with more severe nausea and vomiting and nephrotoxicity; severe
      thrombocytopenia was more frequent during carboplatin-based chemotherapy.
      CONCLUSIONS: Our individual patient data meta-analysis suggests that cisplatin
      based chemotherapy is slightly superior to carboplatin-based chemotherapy in
      terms of response rate and, in certain subgroups, in prolonging survival without
      being associated with an increase in severe toxic effects. Therefore, cisplatin
      based third-generation regimens should remain the standard reference for the
      treatment of selected patients with advanced-stage NSCLC and of those with
      earlier-stage disease.

PMID- 17551146
TI  - A 25-signal proteomic signature and outcome for patients with resected non-small
      cell lung cancer.
AB  - BACKGROUND: Among patients with non-small-cell lung cancer (NSCLC), those with
      poor prognosis cannot be distinguished from those with good prognosis. METHODS:
      Matrix-assisted laser desorption-ionization mass spectrometry was used to analyze
      protein profiles of 174 specimens from NSCLC tumors and 27 specimens from normal
      lung tissue and to derive a prognosis-associated proteomic signature. Frozen
      resected tissue specimens were randomly divided into a training set (116 NSCLC
      and 20 normal lung specimens) and an independent, blinded validation set (58
      NSCLC and seven normal lung specimens). Mass spectrometry signals from training
      set specimens that were differentially associated with specimens from patients
      with a high risk of recurrence (i.e., who died within 5 years of surgical
      treatment because of relapse) compared with those from patients with a low risk
      of recurrence (i.e., alive with no symptoms of relapse after a median follow-up
      of 89 months) were selected by use of the Fisher's exact test, the Kruskal-Wallis
      test, and the significance analysis of microarray test. These signals were used
      to build an individualized, weighted voting-based prognostic signature. The
      signature was then validated in the independent dataset. Survival was assessed by
      multivariable Cox regression analysis. Proteins corresponding to individual
      signals were identified by ion-trap mass spectrometry coupled with high
      performance liquid chromatography. All statistical tests were two-sided. RESULTS:
      From 2630 mass spectrometry signals from specimens in the training cohort, we
      derived a signature of 25 signals that was associated with both relapse-free
      survival and overall survival. Among stage I NSCLC patients in the validation
      set, the signature was statistically significantly associated with both overall
      survival (hazard ratio [HR] of death for patients in the high-risk group compared
      with those in the low-risk group = 61.1, 95% confidence interval [CI] = 8.9 to
      419.2, P<.001) and relapse-free survival (HR of relapse = 11.7, 95% CI = 3.1 to
      44.8, P<.001). Proteins corresponding to signals in the signature were identified
      that had various cellular functions, including ribosomal protein L26-like 1,
      acylphosphatase, and phosphoprotein enriched in astrocytes 15. CONCLUSIONS: We
      defined a mass spectrometry signature that was associated with survival among
      NSCLC patients and appeared to distinguish those with poor prognosis from those
      with good prognosis.

PMID- 17551147
TI  - Analysis of integrin alpha7 mutations in prostate cancer, liver cancer,
      glioblastoma multiforme, and leiomyosarcoma.
AB  - BACKGROUND: Integrins are the major adhesive molecules in mammalian cells. Each
      integrin subtype plays a unique role in cell differentiation and embryo
      development. However, integrin involvement in carcinogenesis has not been well
      defined. METHODS: We identified mutations in integrin alpha7 by sequencing
      genomic DNAs and cDNAs from 122 specimens, including 62 primary human tumor
      samples, four cell lines, and 56 matched normal tissues. We evaluated the tumor
      suppressor activity of integrin alpha7 with colony formation, soft agar colony
      growth, and cell migration assays by forcing its expression in PC-3 and Du145
      prostate cancer cells and SK-UT-1 leiomyosarcoma cells. PC-3 and Du145 xenograft
      tumors with increased levels of integrin alpha7 in severe combined immune
      deficient mice were used to assess the effect of integrin alpha7 on tumor growth
      and metastasis. Immunostaining was used to localize and to measure the level of
      integrin alpha7 in 701 and 141 specimens of prostate and smooth muscle,
      respectively. A meta-analysis of integrin alpha7 mRNA microarray data from four
      studies was performed. Kaplan-Meier analyses were used to assess survival. All
      statistical tests were two-sided. RESULTS: Integrin alpha7 mutations that
      generate truncations were found in specimens of 16 of 28 prostate cancers (57%,
      95% confidence interval [CI] = 37% to 76%), five of 24 hepatocellular carcinomas
      (21%, 95% CI = 7% to 42%), five of six glioblastomas multiforme (83%, 95% CI =
      36% to 99%), and one of four leiomyosarcomas (25%, 95% CI = 0.6% to 81%).
      Integrin alpha7 mutations were associated with increased recurrence of human
      prostate cancer (nine recurrences among 13 patients with integrin alpha7
      mutations versus one among eight without such mutations; odds ratio [OR] = 14,
      95% CI = 1.15 to 782, P = .024) and hepatocellular carcinoma (five recurrences
      among eight patients with integrin alpha7 mutations versus one among 16 without
      such mutations, OR = 21, 95% CI = 1.6 to 1245; P = .007). Forced expression of
      normal integrin alpha7 in prostate cancer and leiomyosarcoma cell lines
      suppressed tumor growth and metastasis both in vitro and in vivo. Focal or no
      integrin alpha7 expression in human prostate cancer and soft tissue
      leiomyosarcoma was associated with a reduction of metastasis-free survival (for
      example, for prostate cancer with focal or no expression, 5-year metastasis-free
      survival was 32%, 95% CI = 24.4% to 40.3%, and for prostate cancer with at least
      weak expression, it was 85%, 95% CI = 79% to 91%; P<.001). Microarray analysis
      indicated that cyclin D kinase inhibitor 3 and GTPase-activating protein may be
      possible targets for integrin alpha7-mediated tumor suppressor activity and
      inhibition of cell motility. CONCLUSION: Integrin alpha7 appears to be a tumor
      suppressor that operates by suppressing tumor growth and retarding migration.

PMID- 17551148
TI  - Association of aspirin and nonaspirin nonsteroidal anti-inflammatory drugs with
      cancer incidence and mortality.
AB  - BACKGROUND: The cancer chemopreventive benefits of aspirin and nonaspirin
      nonsteroidal anti-inflammatory drugs (NSAIDs) are incompletely defined and may
      vary by smoking history. We evaluated associations between aspirin and nonaspirin
      NSAID use with cancer incidence and mortality stratified by smoking history in
      the Iowa Women's Health Study, a prospective cohort of postmenopausal women.
      METHODS: Aspirin and nonaspirin NSAID use was self-reported by questionnaire in
      1992. Cancer incidence and mortality were ascertained by annual linkage to the
      Iowa Surveillance, Epidemiology, and End Results Cancer Registry and death
      certificates. Cox proportional hazards models were used to estimate multivariable
      relative risks (RRs) and 95% confidence intervals (CIs). All statistical tests
      were two-sided. RESULTS: During an average of 10 years of follow-up, 3487
      incident cancer cases and 3581 deaths were observed in the cohort of 22,507
      women. Compared with nonuse, aspirin use was inversely associated with total
      cancer incidence (multivariable-adjusted RR = 0.84, 95% CI = 0.77 to 0.90), with
      age-adjusted incidence rates of 147 and 170 per 10,000 person-years for ever and
      never users, respectively, and was inversely associated with cancer mortality
      (multivariable-adjusted RR = 0.87, 95% CI = 0.76 to 0.99), with age-adjusted
      rates of 47 and 52 per 10,000 person-years. The inverse relationship was stronger
      among former and never smokers than current smokers, although not statistically
      significantly (P = .28). Aspirin use was also inversely associated with coronary
      heart disease mortality (multivariable-adjusted RR = 0.75, 95% CI = 0.64 to
      0.89), with age-adjusted rates of 23 and 30 per 10,000 person-years for ever and
      never users, respectively, and with all-cause mortality (multivariable-adjusted
      RR = 0.82, 95% CI = 0.76 to 0.89), with age-adjusted rates of 126 and 155 per
      10,000 person-years. Nonaspirin NSAID use was not associated with cancer
      incidence or mortality, coronary heart disease mortality, or all-cause mortality.
      CONCLUSIONS: Aspirin use, but not nonaspirin NSAID use, was associated with lower
      risks of cancer incidence and mortality, which was more pronounced among former
      and never smokers than current smokers.

PMID- 17551149
TI  - C-reactive protein and risk of breast cancer.
AB  - Chronic inflammation is hypothesized to be associated with breast cancer
      development. However, data evaluating the association between C-reactive protein
      (CRP), a marker of systemic inflammation, and breast cancer risk are sparse. In
      the Women's Health Study, 27,919 apparently healthy women aged 45 years and older
      who were free of cancer and cardiovascular disease had plasma CRP levels measured
      at baseline. During a mean of 10 years of follow-up, a total of 892 women
      developed invasive breast cancer. All statistical tests were two-sided. Baseline
      plasma CRP level was not statistically significantly associated with breast
      cancer risk (highest versus lowest quintile of CRP, multivariable hazard ratio =
      0.90, 95% confidence interval = 0.71 to 1.16; P(trend) = .19; crude incidence
      rates: 273 versus 305 per 100,000 person-years). Our data suggest that baseline
      plasma CRP levels are not associated with the increased risk of breast cancer in
      apparently healthy women.

PMID- 17551150
TI  - Incidence rates of intra- and extrahepatic cholangiocarcinomas in Denmark from
      1978 through 2002.
AB  - Recent studies from several countries, including the United States, have
      indicated that the incidence rate of intrahepatic cholangiocarcinoma is
      increasing while that of extrahepatic cholangiocarcinoma is decreasing. We
      examined whether such opposing trends could be confirmed in Danish data. We
      computed the nationwide Danish incidence rates of intra- and extrahepatic
      cholangiocarcinomas from January 1, 1978, through December 31, 2002, with data
      from the high-quality Danish Cancer Registry. Incidence rates were standardized
      to the US population in 2000. The study included 1335 patients with intrahepatic
      cholangiocarcinoma and 1269 with extrahepatic cholangiocarcinoma. The Danish
      incidence rates of intra- and extrahepatic cholangiocarcinomas were nearly
      identical throughout the study period. From 1978 through 2002, the incidence rate
      of intrahepatic cholangiocarcinoma decreased from 1.27 (95% confidence interval
      [CI] = 0.96 to 1.58) to 0.46 (95% CI = 0.29 to 0.62) per 100,000 people, and the
      rate of extrahepatic cholangiocarcinoma decreased from 1.05 (95% CI = 0.77 to
      1.34) to 0.74 (95% CI = 0.53 to 0.95). The median age at diagnosis decreased
      during the study period, and the proportion of localized cancers increased. The
      decrease in cholangiocarcinoma incidence rates cannot be explained by time trends
      in known risk factors (e.g., inflammatory bowel disease, diabetes, smoking, or
      thorotrast), but our findings are consistent with a common etiology for intra-
      and extrahepatic cholangiocarcinomas.

PMID- 17551151
TI  - Re: Extended lung cancer incidence follow-up in the Mayo Lung Project and
      overdiagnosis.

PMID- 17551152
TI  - Re: Dietary fat reduction and breast cancer outcome: interim efficacy results
      from the Women's Intervention Nutrition Study.

PMID- 17551155
TI  - Re: Dietary fat reduction and breast cancer outcome: interim efficacy results
      from the Women's Intervention Nutrition Study.

PMID- 17551156
TI  - Re: Prostate cancer in fathers with fewer male offspring: the Jerusalem Perinatal
      Study cohort.

PMID- 17551157
TI  - Re: Prostate cancer in fathers with fewer male offspring: the Jerusalem Perinatal
      Study cohort.

PMID- 17551159
TI  - Rosiglitazone evaluated for cardiovascular outcomes--an interim analysis.
AB  - BACKGROUND: A recent meta-analysis raised concern regarding an increased risk of
      myocardial infarction and death from cardiovascular causes associated with
      rosiglitazone treatment of type 2 diabetes. METHODS: We conducted an unplanned
      interim analysis of a randomized, multicenter, open-label, noninferiority trial
      involving 4447 patients with type 2 diabetes who had inadequate glycemic control
      while receiving metformin or sulfonylurea, in which 2220 patients were assigned
      to receive add-on rosiglitazone (rosiglitazone group), and 2227 to receive a
      combination of metformin plus sulfonylurea (control group). The primary end point
      was hospitalization or death from cardiovascular causes. RESULTS: Because the
      mean follow-up was only 3.75 years, our interim analysis had limited statistical
      power to detect treatment differences. A total of 217 patients in the
      rosiglitazone group and 202 patients in the control group had the adjudicated
      primary end point (hazard ratio, 1.08; 95% confidence interval [CI], 0.89 to
      1.31). After the inclusion of end points pending adjudication, the hazard ratio
      was 1.11 (95% CI, 0.93 to 1.32). There were no statistically significant
      differences between the rosiglitazone group and the control group regarding
      myocardial infarction and death from cardiovascular causes or any cause. There
      were more patients with heart failure in the rosiglitazone group than in the
      control group (hazard ratio, 2.15; 95% CI, 1.30 to 3.57). CONCLUSIONS: Our
      interim findings from this ongoing study were inconclusive regarding the effect
      of rosiglitazone on the overall risk of hospitalization or death from
      cardiovascular causes. There was no evidence of any increase in death from either
      cardiovascular causes or all causes. Rosiglitazone was associated with an
      increased risk of heart failure. The data were insufficient to determine whether
      the drug was associated with an increase in the risk of myocardial infarction.
      (ClinicalTrials.gov number, NCT00379769 [ClinicalTrials.gov].).

PMID- 17551160
TI  - Rosiglitazone--continued uncertainty about safety.

PMID- 17551161
TI  - Rosiglitazone and cardiotoxicity--weighing the evidence.

PMID- 17551162
TI  - The record on rosiglitazone and the risk of myocardial infarction.

PMID- 17551163
TI  - Affective synchrony: individual differences in mixed emotions.
AB  - Most models of affect suggest either inverse or null associations between
      positivity and negativity. Recent work has highlighted situations that sometimes
      lead to mixed positive-negative affect. Focusing on the counterpart to these
      situational factors, the authors explore the individual-difference tendency
      toward mixed emotions, which they term affective synchrony. In five studies, the
      authors show that some individuals demonstrate affective synchrony (overlapping
      experience of positive and negative moods), others a-synchrony (positive and
      negative mood that fluctuate independently), and still others de-synchrony
      (positive and negative moods that function as bipolar opposites). These
      tendencies are stable over time within persons, vary broadly across individuals,
      and are associated with individual differences in cognitive representation of
      self and of emotions.

PMID- 17551164
TI  - Detection of an occult thymoma on 99Tcm-Tetrofosmin myocardial scintigraphy.
AB  - Thymoma is an uncommon tumour, which is often asymptomatic and may be detected
      coincidentally on cross-sectional imaging performed for other reasons. We report
      a case of thymoma detected on myocardial scintigraphy performed for suspected
      coronary artery disease. Extracardiac pathology may be suggested by abnormal non
      cardiac tracer uptake on myocardial scintigraphy. An awareness of the potential
      causes of this is essential to allow potentially life threatening non-cardiac
      disorders to be recognized and treated promptly.

PMID- 17551165
TI  - Acute ventricular and aortic thrombosis post chemotherapy.
AB  - We present a rare case of spontaneous arterial thrombosis in a 42-year-old male
      with an acute history of bilateral lower limb pain and weakness. The previous day
      he had received the first cycle of cisplatin-based chemotherapy for oesophageal
      adenocarcinoma (T2/3N0/M0). Computed tomography (CT) and angiography showed
      extensive abdominal aortic thrombus in a native non-aneurysmal or grossly
      atheromatous aorta with separate thrombus in the left ventricle. We suggest that
      poor left ventricular function, a hypercoaguable state secondary to malignancy
      and cisplatin based chemotherapy may have induced severe arterial and intra
      cardiac thrombosis.

PMID- 17551166
TI  - Lower limb ischaemia caused by fractured osteochondroma of the femur.
AB  - Osteochondroma is the most common benign bone tumour and can arise in any bone.
      They frequently develop around the knee in the distal femur and the proximal
      tibia. These are usually asymptomatic, but can occasionally impinge on the
      surrounding vessels and cause various clinical manifestations. We have
      encountered a patient with multiple hereditary exostoses, in whom the
      osteochondroma located in the distal portion of the femur fractured as a result
      of an injury from a traffic accident. The migrated osteochondroma compressed the
      femoral artery and led to an acute onset of lower extremity ischaemia. Although
      trauma or vigorous exercise can cause vascular complications caused by
      osteochondroma, vascular insufficiency due to fracture of osteochondroma after a
      traumatic injury is extremely rare.

PMID- 17551167
TI  - Endovascular therapy for massive haemothorax caused by ruptured extracranial
      vertebral artery aneurysm with neurofibromatosis Type 1.
AB  - Extracranial vertebral artery aneurysm is uncommon, and the common cause is
      penetrating trauma. Rupture of extracranial vertebral artery aneurysm into the
      thoracic cavity is extremely rare and fatal due to haemorrhagic shock by massive
      haemothorax. We report an intrathoracic rupture of the extracranial vertebral
      artery aneurysm with neurofibromatosis Type 1, successfully treated by coil and
      liquid embolisation.

PMID- 17551168
TI  - Solitary liver lesion in a patient with blunt abdominal trauma.

PMID- 17551170
TI  - High-sensitivity detection and quantitative analysis of native protein-protein
      interactions and multiprotein complexes by flow cytometry.
AB  - Most mechanisms of cell development, physiology, and signal transduction are
      controlled by protein-protein interactions. Immunoprecipitation of multiprotein
      complexes detected by flow cytometry (IP-FCM) is a means to quantitatively
      measure these interactions. The high sensitivity of this method makes it useful
      even when very little biomaterial is available for analysis, as in the case of
      rare primary cell subsets or patient samples. Detection of the T cell antigen
      receptor associated with the CD3 multiprotein complex from as few as 300 primary
      murine T cells is presented as an example. The method is compatible with
      quantitative flow cytometry techniques, making it possible to estimate the number
      of coimmunoprecipitated molecules. Both constitutive and inducible protein
      protein interactions can be analyzed, as illustrated in related methodology using
      glutathione S-transferase-fusion protein pull-down experiments. IP-FCM represents
      a robust, quantitative, biochemical technique to assess native protein-protein
      interactions, without requiring genetic engineering or large sample sizes.

PMID- 17551171
TI  - Instructions for the Clinical Scale for Contraversive Pushing (SCP).

PMID- 17551172
TI  - Upper extremity lymphedema after treatment for breast cancer: a review of the
      literature.
AB  - Upper extremity lymphedema - a common, poorly understood, and relatively
      understudied complication of cancer therapy - is a progressive and debilitating
      condition for which no cure is available. While advances in cancer treatment have
      lowered the incidence of lymphedema, lymph node trauma is often inevitable and
      the number of cancer survivors and elderly are increasing. A review of the
      literature suggests that research is needed to better understand the incidence
      and magnitude of upper extremity lymphedema; develop reliable and valid
      lymphedema risk assessment instruments; improve collaborative research efforts
      among skin, wound, and cancer investigators; and develop evidence-based
      lymphedema prevention and treatment protocols. Currently available evidence also
      indicates that increased clinician and patient awareness and education may help
      reduce the risk of lymphedema-associated complications through early detection
      and prompt interventions.

PMID- 17551173
TI  - Use of human and porcine dermal-derived bioprostheses in complex abdominal wall
      reconstructions: a literature review and case report.
AB  - The goal of abdominal wall reconstruction is to restore and maintain abdominal
      domain. A PubMed(R) review of the literature (including "old" MEDLINE through
      February 2007) suggests that bioprosthetic materials are increasingly used to
      facilitate complex abdominal wall reconstruction. Reported results (eight case
      reports/series involving 137 patients) are encouraging. The most commonly
      reported complications are wound seroma (18 patients, 13%), skin dehiscence with
      graft exposure without herniation (six, 4.4%), superficial and deep wound
      infections (five, 3.6%), hernia recurrence (four, 2.9%), graft failure with
      dehiscence (two), hematoma (two), enterocutaneous fistula (one), and flap
      necrosis (one). Two recent cases are reported herein. In one, a 46-year-old woman
      required open abdominal management after gastric remnant perforation following a
      Roux-en-Y gastric bypass procedure. Porcine dermal collagen combined with
      cutaneous flaps was used for definitive abdominal wall reconstruction. The
      patient's condition improved postoperatively and she was well 5 months after
      discharge from the hospital. In the second, a 54-year-old woman underwent repair
      of an abdominal wall defect following resection of a large leiomyosarcoma. Human
      acellular dermis combined with myocutaneous flaps was used to reconstruct the
      abdominal wall defect. The patient's recovery was uncomplicated and 20 weeks
      following surgery she was doing well with no evidence of recurrence or hernia.
      The results reported to date and the outcomes presented here suggest that
      bioprosthetic materials are safe and effective for repair of large abdominal wall
      defects. Prospective, randomized, controlled studies are needed to compare the
      safety and efficacy of other reconstructive techniques as well as human and
      porcine dermal-derived bioprostheses.

PMID- 17551174
TI  - Using negative pressure wound therapy following surgery for complex pilonidal
      disease: a case series.
AB  - Complex pilonidal disease, an uncommon manifestation of an anorectal condition,
      is characterized by chronic or recurrent abscesses with extensive, branching
      sinus tracts. Definitive treatment requires wide excision of all involved tissue
      followed by secondary intention healing or reconstructive surgery. All treatment
      options have unique advantages and disadvantages. Following recent reports that
      negative pressure wound therapy after surgery for complex pilonidal disease may
      be a useful alternative to moist saline dressing treatments, five patients (three
      men and two women, median age 21 years [range: 16 to 63 years]) with complex
      pilonidal disease (symptom duration range 6 months to 30 years) were treated on
      an outpatient basis. Following wide excision under general anesthesia, a portable
      negative pressure wound therapy device was applied. Mean wound defect size after
      excision was 11 cm x 4 cm x 5 cm, or 205 cm(3) (range 90 cm(3) to 410 cm(3)).
      Negative pressure wound therapy was used for an average of 6 weeks (range 4 to 9
      weeks) and mean time to complete epithelialization was 12 weeks (range 9 to 22
      weeks), including use of moist saline dressings post negative pressure wound
      therapy. Treatment was discontinued in one patient due to skin irritation. No
      other complications were observed. Long-term follow-up is required to assess the
      risk of recurrent pilonidal disease or wound failure following negative pressure
      wound therapy. Additional studies of negative pressure wound therapy in the
      management of pilonidal disease are warranted.

PMID- 17551175
TI  - Metallophilic interactions in iodido(2,2':6',2''-terpyridine)platinum(II)
      diiodidoaurate(I).
AB  - In the title compound, [PtI(C(15)H(11)N(3))][AuI(2)], the [PtI(terpy)](+) cations
      (terpy is 2,2':6',2''-terpyridine) stack in pairs about inversion centers through
      Pt...Pt interactions of 3.5279 (5) A. The [AuI(2)](-) anions also exhibit
      pairwise stacking, with Au...I distances of 3.7713 (5) A. The [PtI(terpy)](+)
      cations and [AuI(2)](-) anions aggregate forming infinite arrays of stacked
      ...([[PtI(terpy)](+)...[PtI(terpy)](+)]...[[AuI(2)](-)...[AuI(2)](-)])... units.

PMID- 17551176
TI  - Poly[tetraphenylphosphonium copper(I)-di-micro2-dicyanamido].
AB  - In the title compound, [(C(24)H(20)P)[Cu(C(2)N(3))(2)]](n), the copper(I)
      dicyanamide anion forms a distorted three-dimensional single diamondoid network.
      Templating tetraphenylphosphonium cations reside within the cavities of the
      polymeric anion.

PMID- 17551177
TI  - trans-Dichloridotetrakis(3,5-dimethylpyridine)copper(II).
AB  - The title compound, [CuCl(2)(C(7)H(9)N)(4)], lies on a site of crystallographic
      42 (D(4)) symmetry in the space group P4/nnc, and is isomorphous with the Ni and
      Co analogues. The Cu and Cl atoms thus lie on a fourfold axis, and the 3,5
      lutidine ligands lie on twofold axes. The Cu-Cl distance is 2.7649 (7) A and the
      Cu-N distance is 2.0510 (12) A. The space group of the Co analogue is revised
      from Pnnn to P4/nnc.

PMID- 17551178
TI  - mer-Diaquabis(1H-imidazole-kappaN3)[orotato(2-)]cobalt(II).
AB  - In the title complex, mer-diaqua[2,6-dioxo-1,2,3,6-tetrahydropyrimidine-4
      carboxylato(2-)]bis(1H-imidazole-kappaN(3))cobalt(II),
      [Co(C(5)H(2)N(2)O(4))(C(3)H(4)N(2))(2)(H(2)O)(2)], the Co(II) ion is coordinated
      by a deprotonated N atom and the carboxylate O atom of the orotate ligand, two
      imidazole N atoms and two aqua ligands in a distorted octahedral geometry. The
      title complex exists as discrete doubly hydrogen-bonded dimers, and a three
      dimensional network of O-H...O and N-H...O hydrogen bonds and weak pi-pi
      interactions is responsible for crystal stabilization.

PMID- 17551179
TI  - Diaquabis(4-fluorobenzoato-kappaO)bis(nicotinamide-kappaN)cobalt(II).
AB  - The title compound, [Co(C(7)H(4)FO(2))(2)(C(6)H(6)N(2)O)(2)(H(2)O)(2)], is a
      three-dimensional hydrogen-bonded supramolecular complex. The Co(II) ion resides
      on a centre of symmetry and is in an octahedral coordination environment
      comprising two pyridyl N atoms, two carboxylate O atoms and two O atoms from
      water molecules. Intermolecular N-H...O and O-H...O hydrogen bonds produce
      R(3)(2)(6), R(2)(2)(12) and R(2)(2)(16) rings, which lead to two-dimensional
      chains. An extensive three-dimensional network of C-H...F, N-H...O and O-H...O
      hydrogen bonds and pi-pi interactions are responsible for crystal stabilization.

PMID- 17551180
TI  - A novel two-dimensional layered framework built of strontium(II) with 4
      nitrobenzene-1,3-dicarboxylic acid.
AB  - In poly[[aquastrontium(II)]-micro(6)-4-nitrobenzene-1,3-dicarboxylato
      kappa(7)O(1):O(2):O(2):O(3):O(3),O(4):O(4)], [Sr(C(8)H(3)NO(6))(H(2)O)](n), the
      Sr(II) ion displays a distorted bicapped triangular prismatic configuration,
      defined by seven carboxyl O atoms from six symmetry-related ligands and one water
      molecule. The ligand molecules connect the Sr(II) ions into a two-dimensional
      layered framework in the ac plane, with close O...O contacts between the nitro
      groups and with each nitro group providing one acceptor O atom for a weak
      intermolecular C-H...O hydrogen bond.

PMID- 17551181
TI  - Two polymorphic forms of a mixed zinc/copper biquinoline dihydrogenphosphate.
AB  - Two polymorphic forms of a mixed zinc/copper biquinoline dihydrogenphosphate are
      presented, showing almost identical monomeric units, viz. (2,2'-biquinoline
      kappa(2)N,N')bis(dihydrogenphosphato-kappaO)copper(II)/zinc(II), formulated as
      [Zn(x)Cu(1-x)(H(2)PO(4))(2)(C(18)H(12)N(2))], with x = 0.88 (1) and 0.90 (2). The
      cation is tetrahedrally coordinated to a chelating biquinoline system and two
      diprotonated phosphate anions. The structures differ mainly in their
      intermolecular hydrogen-bonding interactions, leading to different packing
      schemes. No significant evidence of stress due to the Zn/Cu solid solution
      formation was detected.

PMID- 17551182
TI  - An organouranium coordination polymer containing infinite metal oxide chains.
AB  - The title compound, catena-poly[[[dioxouranium(VI)]-bis(micro-2
      hydroxybenzohydroxamato)] dihydrate], [[U(C(7)H(6)NO(3))(2)O(2)].2H(2)O](n), is a
      uranyl coordination polymer based on the salicylhydroxamate ligand. The ligand
      acts both as a chelate, forming five-membered rings, and as a bridge between two
      U atoms. The coordination around each U atom is a distorted hexagonal bipyramid.
      Infinite chains running along [001] are formed via bridging salicylhydroxamate O
      atoms. The chains have C(2) symmetry, with U atoms in special positions on
      twofold axes. The water molecules are not coordinated to the metal but crosslink,
      through hydrogen bonding, adjacent coordination polymer chains in the [110] and
      [110] directions.

PMID- 17551183
TI  - Poly[propane-1,3-diammonium [tetra-micro3-oxo-hexaoxotrimolybdenum(VI)]
      dihydrate].
AB  - The crystal structure of the title compound,
      [(C(3)H(12)N(2))[Mo(3)O(10)].2H(2)O](n), is composed of [Mo(3)O(10)](2-) anionic
      chains, propane-1,3-diammonium cations and solvent water molecules. The
      [Mo(3)O(10)](2-) chain is constructed from edge-sharing MoO(6) octahedra. The
      protonated propane-1,3-diamine cations and solvent water molecules are located
      between the chains and are linked to the O atoms of the inorganic chains by
      hydrogen bonds.

PMID- 17551184
TI  - Silver(I) sulfate coordination polymers with 4,4'-bipyridazine and pyridazino[4,5
      d]pyridazine.
AB  - Poly[[micro(4)-4,4'-bipyridazine-micro(5)-sulfato-disilver(I)] monohydrate],
      [[Ag(2)(SO(4))(C(8)H(6)N(4))].H(2)O](n), (I), and poly[[aqua-micro(4)
      pyridazino[4,5-d]pyridazine-micro(3)-sulfato-disilver(I)] monohydrate],
      [[Ag(2)(SO(4))(C(6)H(4)N(4))(H(2)O)].H(2)O](n), (II), possess three- and two
      dimensional polymeric structures, respectively, supported by N-tetradentate
      coordination of the organic ligands [Ag-N = 2.208 (3)-2.384 (3) A] and O
      pentadentate coordination of the sulfate anions [Ag-O = 2.284 (3)-2.700 (2) A].
      Compound (I) is the first structurally examined complex of the new ligand 4,4'
      bipyridazine; it is based upon unprecedented centrosymmetric silver-pyridazine
      tetramers with tetrahedral AgN(2)O(2) and trigonal-bipyramidal AgN(2)O(3)
      coordination of two independent Ag(I) ions. Compound (II) adopts a typical
      dimeric silver-pyridazine motif incorporating two kinds of square-pyramidal
      AgN(2)O(3) Ag(I) ions. The structure exhibits short anion-pi interactions
      involving noncoordinated sulfate O atoms [O...pi = 3.041 (3) A].

PMID- 17551185
TI  - (2,6-Bis[1-[4
      (dimethylamino)phenylimino]ethyl]pyridine)dichlorido(triphenylphosphine
      kappaP)ruthenium(II): a zigzag chain of fused centrosymmetric R(2)(2)(12) rings.
AB  - The title compound, [RuCl(2)(C(25)H(29)N(5))(C(18)H(15)P)], a transfer
      hydrogenation catalyst, is supported by an N,N',N''-tridentate pyridine-bridged
      ligand and triphenylphosphine. The Ru(II) centre is six-coordinated in a
      distorted octahedral arrangement, with the two Cl atoms located in the axial
      positions, and the pyridine (py) N atom, the two imino N atoms and the
      triphenylphosphine P atom located in the equatorial plane. The two equatorial Ru
      N(imino) distances (mean 2.093 A) are substantially longer than the equatorial Ru
      N(py) bond [1.954 (4) A]. It is observed that the N(imino)-M-N(py) bond angle for
      the five-membered chelate rings of 2,6-bis(imino)pyridine-based complexes is
      inversely related to the magnitude of the M-N(py) bond. The title structure is
      stabilized by intra- and intermolecular C-H...Cl hydrogen bonds, as well as by
      intramolecular pi-pi stacking interactions between the aromatic rings belonging
      to the triphenylphosphine ligand and the dimethylaminophenyl fragment. The
      intermolecular hydrogen bonds form an R(2)(2)(12) ring and a zigzag chain of
      fused centrosymmetric rings running parallel to the [100] direction.

PMID- 17551186
TI  - A novel helical copper complex: catena-poly[[[aquacopper(II)]-micro-N-(3-carboxy
      2-oxidobenzylidene-kappaO2)glycinato-kappa3N,O':O'] monohydrate].
AB  - In the polymeric title compound, [[Cu(C(10)H(7)NO(5))(H(2)O)].H(2)O](n), the Cu
      atom adopts a square-based pyramidal coordination involving a N,O,O'-tridentate
      glycine dianionic ligand, a water O atom and an apical bridging carboxylate O
      atom from an adjacent ligand. The title compound also adopts a carboxylate
      bridged chain structure. The molecular chain propagates in a helical fashion
      along the b axis of the monoclinic unit cell. Neighbouring chains are linked
      together to form a three-dimensional network via hydrogen-bonding interactions
      between coordinated and uncoordinated water molecules and O atoms of the bridging
      carboxylate groups.

PMID- 17551187
TI  - catena-Poly[[diaquazinc(II)]-micro-4,4'-sulfonyldibenzoato-kappa2O:O'].
AB  - The title compound, [Zn(C(14)H(8)O(6)S)(H(2)O)(2)](n), is the first reported
      metal complex of the 4,4'-sulfonyldibenzoate anion. The structure comprises
      zigzag chains of alternating [Zn(H(2)O)(2)](2+) and sulfonyldibenzoate units, the
      central Zn and S atoms of which lie on crystallographic twofold axes. The Zn(II)
      centre occupies a strongly distorted tetrahedral environment [O-Zn-O = 83.30 (7)
      136.19 (8) degrees], coordinated by the two water O atoms [Zn-O = 1.986 (2) A]
      and one O atom from each of two carboxylate groups [Zn-O = 1.9942 (19) A], with
      much longer contacts to the other O atoms of these carboxylates [Zn-O = 2.528 (2)
      A]. Hydrogen bonds between carboxylate O atoms and coordinated water molecules in
      adjacent chains lead to the formation of a three-dimensional network structure.

PMID- 17551188
TI  - Two pseudo-polymorphic copper-benzene-1,2,4,5-tetracarboxylate complexes.
AB  - Two pseudo-polymorphic polymers, poly[ethylenediammonium [[aquacopper(II)]
      micro(4)-benzene-1,2,4,5-tetracarboxylato] dihydrate],
      [(C(2)H(10)N(2))[Cu(C(10)H(2)O(8))(H(2)O)].2H(2)O](n), (I), and
      poly[ethylenediammonium [copper(II)-micro(4)-benzene-1,2,4,5-tetracarboxylato]
      2.5-hydrate], [(C(2)H(10)N(2))[Cu(C(10)H(2)O(8))].2.5H(2)O](n), (II), contain two
      dimensional anionic layers, ethylenediammonium (H(2)en) cations acting as counter
      ions and free water molecules. Although the topological structures of the two
      anionic layers are homologous, the coordination environments of the Cu(II)
      centres are different. In (I), the Cu(II) centre, sitting on a general position,
      has a square-pyramidal environment. The two independent benzene-1,2,4,5
      tetracarboxylate (btc) anions rest on centres of inversion. The Cu(II) cation in
      (II) is located on a twofold axis in a square-planar coordination. The H(2)en
      cation is on an inversion centre and the btc ligand is split by a mirror plane.
      Extensive hydrogen-bonding interactions between the complexes, H(2)en cations and
      water molecules lead to the formation of three-dimensional supramolecular
      structures.

PMID- 17551189
TI  - trans-[1,3-Bis(2,4,6-trimethylphenyl)imidazolidin-2
      ylidene]dichlorido(triphenylphosphine-kappaP)palladium(II).
AB  - The title complex, [PdCl(2)(C(21)H(26)N(2))(C(18)H(15)P)], shows slightly
      distorted square-planar coordination around the Pd(II) metal centre. The Pd-C
      bond distance between the N-heterocyclic ligand and the metal atom is 2.028 (5)
      A. The dihedral angle between the two trimethylphenyl ring planes is 36.9 (2)
      degrees.

PMID- 17551190
TI  - Dimethyl 2,2'-bipyridine-6,6'-dicarboxylate and bis(dimethyl 2,2'-bipyridine-6,6'
      dicarboxylato-kappa2N,N')copper(I) tetrafluoroborate.
AB  - The single-crystal X-ray structures of dimethyl 2,2'-bipyridine-6,6'
      dicarboxylate, C(14)H(12)N(2)O(4), and the copper(I) coordination complex
      bis(dimethyl 2,2'-bipyridine-6,6'-dicarboxylato-kappa(2)N,N')copper(I)
      tetrafluoroborate, [Cu(C(14)H(12)N(2)O(4))(2)]BF(4), are reported. The
      uncoordinated ligand crystallizes across an inversion centre and adopts the
      anticipated anti pyridyl arrangement with coplanar pyridyl rings. In contrast,
      upon coordination of copper(I), the ligand adopts an arrangement of pyridyl
      donors facilitating chelating metal coordination and an increased inter-pyridyl
      twisting within each ligand. The distortion of each ligand contrasts with
      comparable copper(I) complexes of unfunctionalized 2,2'-bipyridine.

PMID- 17551191
TI  - Inclusion of chlorophenols by 4,4'-(cyclohexane-1,1-diyl)diphenol: structures and
      kinetics of decomposition.
AB  - The structures of the inclusion compounds 4,4'-(cyclohexane-1,1-diyl)diphenol-3
      chlorophenol (1/1) and 4,4'-(cyclohexane-1,1-diyl)diphenol-4-chlorophenol (1/1),
      both C(18)H(20)O(2).C(6)H(5)ClO, are isostructural with respect to the host
      molecule and are stabilized by extensive host-host, host-guest and guest-host
      hydrogen bonding. The packing is characterized by layers of host and guest
      molecules. The kinetics of thermal decomposition follow the R2 contracting-area
      model, kt = [1 - (1 - alpha)1/2], and yield activation energies of 105 (8) and 96
      (8) kJ mol(-1), respectively.

PMID- 17551192
TI  - Polymorph VI of sulfapyridine: interpenetrating two- and three-dimensional
      hydrogen-bonded nets formed from two tautomeric forms.
AB  - Polymorph VI of 4-amino-N-(2-pyridyl)benzenesulfonamide, C(11)H(11)N(3)O(2)S, is
      monoclinic (space group P2(1)/n). The asymmetric unit contains two different
      tautomeric forms. The structure displays N-H...N and N-H...O hydrogen bonding.
      The two independent molecules form two separate two- and three-dimensional
      hydrogen-bonded networks which interpenetrate. The observed patterns of hydrogen
      bonding are analogous to those in polymorph I of sulfathiazole.

PMID- 17551193
TI  - Violuric acid monohydrate: a second polymorph with more extensive hydrogen
      bonding.
AB  - Crystals of a second polymorph of violuric acid monohydrate [systematic name:
      pyrimidine-2,4,5,6(1H,3H)-tetrone monohydrate], C(4)H(3)N(3)O(4).H(2)O, have
      higher density and a more extensive hydrogen-bonding arrangement than the
      previously reported polymorph. Violuric acid and water molecules form essentially
      planar hydrogen-bonded sheets, which are stacked in an offset ...ABCABC... repeat
      pattern involving no ring-stacking interactions.

PMID- 17551194
TI  - 3,17-Dioxoandrost-4-en-4-yl acetate.
AB  - The title compound, C(21)H(28)O(4), has a 4-acetoxy substituent positioned on the
      steroid alpha face. The six-membered ring A assumes a conformation intermediate
      between 1alpha,2beta-half chair and 1alpha-sofa. A long Csp(3)-Csp(3) bond is
      observed in ring B and reproduced in quantum-mechanical ab initio calculations of
      the isolated molecule using a molecular-orbital Hartree-Fock method. Cohesion of
      the crystal can be attributed to van der Waals interactions and weak C-H...O
      hydrogen bonds.

PMID- 17551195
TI  - 3-(3-Oxo-1,3-dihydroisobenzofuran-1-ylidene)pentane-2,4-dione.
AB  - In the title compound, C(13)H(10)O(4), prepared by the condensation reaction
      between phthalic anhydride and pentane-2,4-dione, one of the acetyl groups in the
      pentane-2,4-dione fragment is almost coplanar with the isobenzofuran ring system,
      while the other group is twisted out of this plane by almost 80 degrees . The
      corresponding C-C and C-O distances in the two acetyl units are consistent with
      dipolar delocalization into the coplanar unit only. There is no supramolecular
      aggregation of the molecules, but a number of rather short intermolecular
      contacts of C-H...O, O...O and O...C types occur.

PMID- 17551196
TI  - N-(4-nitrobenzoyl)-N'-phenylhydrazine: a three-dimensional hydrogen-bonded
      framework.
AB  - In the title compound (systematic name: N-anilino-4-nitrobenzamide),
      C(13)H(11)N(3)O(3), the molecules are linked into a complex three-dimensional
      framework structure by a combination of two-centre N-H...O and C-H...O hydrogen
      bonds and a three-centre N-H...(O,N) hydrogen bond.

PMID- 17551197
TI  - C--H...O hydrogen-bonding and C--H...pi interactions in 3-(4-fluorophenyl)-1,5,7
      trimethyl-1,2,3,4-tetrahydropyrido[2,3-d]pyrimidine-2,4-dione.
AB  - In the title compound, C(16)H(14)FN(3)O(2), a diverse set of weak intermolecular
      C--H...pi, pi-pi and C--H...O interactions link the molecules into sheets. The C-
      H...O interactions generate centrosymmetric rings with a graph-set motif of
      R(2)(2)(14) and chains with a C(8) motif.

PMID- 17551198
TI  - 3-(4-Bromophenyl)-5-(4-dimethylaminophenyl)-1-phenyl-2-pyrazoline: X-ray and
      density functional theory (DFT) studies.
AB  - In the crystal structure of the title compound, C(23)H(22)BrN(3), a strong
      conjugation of the pyrazoline chromophore with the aromatic rings at positions 1
      and 3 is observed, as well as a significant shift in the synclinal-
      >synperiplanar direction. The absolute structure was unequivocally determined. In
      the absence of clasical hydrogen-bond donors, the structure is stabilized by weak
      C-H...pi interactions. This paper also reports the electronic structure of the
      title compound using NBO (natural bond order) analysis. The contributions of lone
      pairs to the relevant bonds were revealed.

PMID- 17551199
TI  - Ring opening of pyridines: the pseudo-cis and pseudo-trans isomers of tetra-n
      butylammonium 4-nitro-5-oxo-2-pentenenitrilate.
AB  - The reaction of 2-chloro-5-nitropyridine with two equivalents of base produces
      the title carbanion as an intermediate in a ring-opening/ring-closing reaction.
      The crystal structures of the tetra-n-butylammonium salts of the intermediates,
      C(16)H(36)N(+).C(5)H(3)N(2)O(3)(-), revealed that pseudo-cis and pseudo-trans
      isomers are possible. One crystal structure displayed a mixture of the two
      isomers with approximately 90% pseudo-cis geometry and confirms the structure
      predicted by the S(N)(ANRORC) mechanism. The pseudo-cis intermediate undergoes a
      slow isomerization over a period of months to the pseudo-trans isomer, which does
      not have the appropriate geometry for the subsequent ring-closing reaction. The
      structure of the pure pseudo-trans isomer is also reported. In both isomers, the
      negative charge is highly delocalized, but relatively small differences in C-C
      bond distances indicate a system of conjugated double bonds with the nitro group
      bearing the negative charge. The packing of the two unit cells is very similar
      and largely determined by the interactions between the planar carbanion and the
      bulky tetrahedral cation.

PMID- 17551200
TI  - Tris(thianthrene)2+ bis(dodecamethylcarba-closo-dodecaborate) dichloromethane
      tetrasolvate: a crossed triple-decker pi-trimer dication.
AB  - The title compound, (3C(12)H(8)S(2))(2+).2C(13)H(36)B(11)(-).4CH(2)Cl(2),
      contains an unusual cation-radical association comprising a pi-trimer dication of
      crossed thianthrenes. The thianthrene molecular planes are essentially cofacial,
      but the S...S axes of adjacent molecules are orthogonal to each other. The outer
      thianthrenes (both located on mirror planes bisecting the units at the S atoms)
      are bent slightly towards the inner and planar thianthrene (residing on a 2/m
      symmetry element with the S atoms on the twofold rotation axis), with close
      noncovalent separations of 3.1 A indicating strong interplanar interactions
      within the trimeric dication. Bond-length analysis indicates that the 2+ charge
      is delocalized over the three stacked thianthrenes with the maximum charge on the
      central unit. The crossed monomer arrangement is attributed to the frontier
      orbital symmetry that allows various pi-bonding orientations between thianthrene
      molecules. The CB(11)(CH(3))(12)(-) counter-ion resides on a mirror plane. One of
      the CH(2)Cl(2) solvent molecules resides on a twofold rotation axis, whereas the
      other is located on a mirror plane.

PMID- 17551201
TI  - A fluoresceinophane: 1(9),4,16-trioxa-1(2,10)-anthracena-2(1,2)
      benzenacyclohexadecaphane-1(7),3(1(9)H)-dione.
AB  - A novel macrocycle containing fluorescein, the highly fluorescent title compound,
      C(31)H(32)O(5), has a xanthene core and a benzyl unit that are planar. The latter
      is rotated by 72.99 (3) degrees from the xanthene mean plane. The C(11) alkyl
      tether and the xanthene group adopt a cage-like structure and the xanthene adopts
      a quinoid-type configuration. The compound crystallizes as a racemic mixture with
      one molecule of each isomer per unit cell. Even though the planes described by
      the xanthene and the benzene rings of different molecules are separated by 3.341
      (4) and 3.73 (1) A, respectively, there is insufficient overlap between the aryl
      units to promote pi-stacking.

PMID- 17551202
TI  - Conformational enantiomeric disorder in tripivaloylmethane.
AB  - Tripivaloylmethane [systematic name: 4-(2,2-dimethylpropanoyl)-2,2,6,6
      tetramethylheptane-3,5-dione], C(16)H(28)O(3), is a 1,3,3'-triketone with C(3)
      molecular symmetry, prepared by alpha-acylation of 2,2,6,6-tetramethylheptane-3,5
      dione with 2,2-dimethylpropanoyl anhydride in the presence of barium metal. The
      molecules are conformationally chiral and pack so that each molecular site is
      occupied with equal probability by the two enantiomers. The carbonyl groups of
      the two superimposed enantiomeric molecules are at an angle of 75.4 (16) degrees
      .

PMID- 17551203
TI  - A new gamma-polymorph of chlorpropamide: 4-chloro-N
      (propylaminocarbonyl)benzenesulfonamide.
AB  - The structure of a new polymorph of the title compound, C(10)H(13)ClN(2)O(3)S,
      known as the antidiabetic drug chlorpropamide, is monoclinic, in contrast with
      the two previously described orthorhombic alpha- and beta-forms. The molecules in
      the gamma-polymorph are linked into bands by hydrogen bonds similar to those in
      the alpha-polymorph. The conformation of the molecules in the gamma-form is close
      to that in the beta-polymorph.

PMID- 17551204
TI  - 4-(Pyrrol-1-yl)-1,2,4-triazole.
AB  - The asymmetric unit of the title compound, C(6)H(6)N(4), comprises one and a half
      molecules with a C(2) axis through the second molecule. Each molecule consists of
      two planar five-membered rings connected by a triazole-pyrrole N-N bond with the
      triazole ring close to being at right angles to the pyrrole ring. The molecules
      are linked by C-H...N hydrogen bonds and weaker offset face-to-face pi-pi
      interactions.

PMID- 17551205
TI  - The experimental library multipolar atom model refinement of L-aspartic acid.
AB  - The crystal structure of L-aspartic acid, C(4)H(7)NO(4), has been determined
      using two types of refinement, viz. the standard independent atom model (IAM) and
      the experimental library multipolar atom model (ELMAM). The ELMAM refinement
      shows a good improvement of the statistical indices compared with the IAM model,
      notably in terms of thermal displacement parameters and bond distances involving
      H atoms.

PMID- 17551206
TI  - 2,2-Dimethyl-5-nitroso-1,3-dioxan-5-yl benzoate, 2,2-dimethyl-5-nitroso-1,3
      dioxan-5-yl 4-chlorobenzoate and 5-nitroso-1,3-dioxan-5-yl 4-chlorobenzoate.
AB  - The crystal structures of 2,2-dimethyl-5-nitroso-1,3-dioxan-5-yl benzoate,
      C(13)H(15)NO(5), (I), 2,2-dimethyl-5-nitroso-1,3-dioxan-5-yl 4-chlorobenzoate,
      C(13)H(14)ClNO(5), (II), and 5-nitroso-1,3-dioxan-5-yl 4-chlorobenzoate,
      C(11)H(11)NO(5), (III), have been determined in order to gain insight into the
      conformational preference of alpha-benzoyloxynitroso. Unfavourable 1,3-diaxial
      interactions force (I) and (II) to crystallize in the 2,5 twist-boat
      conformation, whereas compound (III), lacking this destabilizing interaction,
      crystallizes in the chair conformation.

PMID- 17551207
TI  - 2,6-Bis[(2-hydroxy-3-methoxybenzylidene)hydrazinocarbonyl]pyridine monohydrate.
AB  - In the title compound, C(23)H(19)N(5)O(6).H(2)O, the two components are linked
      into complex chains by a combination of two independent O-H...O and two
      independent N-H...O hydrogen bonds. The complex chains are linked into a two
      dimensional sheet network via pi-pi stacking interactions and C-H...O hydrogen
      bonds.

PMID- 17551208
TI  - New aromatic nitro compounds from Salegentibacter sp. T436, an Arctic Sea ice
      bacterium: taxonomy, fermentation, isolation and biological activities.
AB  - Nineteen aromatic nitro compounds were isolated from the culture broth of an
      Arctic sea ice bacterium. Four of these compounds are new and six compounds are
      reported from a natural source for the first time. The new natural products
      showed weak antimicrobial and cytotoxic activities. 2-nitro-4-(2'-nitroethenyl)
      phenol was the most potent antimicrobial and cytotoxic substance. Some of the
      compounds exhibit plant growth modulating activities. Based on its biochemical
      properties and the 16S rRNA gene sequence, the producing strain can be described
      as a distinct species within the genus Salegentibacter.

PMID- 17551209
TI  - Fusaristatins A and B, two new cyclic lipopeptides from an endophytic Fusarium
      sp.
AB  - Two new cyclic lipopeptides, fusaristatins A (1) and B (2) were isolated from
      rice cultures of a Fusarium sp. YG-45 in the course of a screening of endophytic
      fungi. Their structures of 1 and 2 were determined by spectroscopic methods. 2
      showed a moderate inhibitory effect on topoisomerases I (IC50: 73 microM) and II
      (IC50: 98 microM) without cleavable complexes. Furthermore, 1 and 2 showed the
      growth-inhibitory activity toward lung cancer cells LU 65 with IC50 values of 23
      and 7 microM, respectively.

PMID- 17551210
TI  - Two new bisorbicillinoids isolated from a deep-sea fungus, Phialocephala sp.
      FL30r.
AB  - Two new bisorbicillinoids, named oxosorbiquinol (1) and dihydrooxosorbiquinol
      (2), were isolated from a deep-sea fungus, Phialocephala sp., and their
      structures established using spectroscopic methods. The absolute configurations
      of 1 and 2 were determined by their biosynthesis route and analysis of the CD
      spectrum. Their cytotoxic effects on P388, A-549, HL60, BEL7402 and K562 cell
      lines were examined by the MTT method.

PMID- 17551211
TI  - New aureothin derivative, alloaureothin, from Streptomyces sp. MM23.
AB  - A new polypropionate alloaureothin (1) possessing a nitro group, together with a
      known polypropionate aureothin (2), was isolated from mycelium of Streptomyces
      sp. MM23. The structure was determined on the basis of spectroscopic data. 1
      exhibited growth inhibitory effect against human fibrosarcoma HT1080 cells with
      an IC50 value of 30 microM.

PMID- 17551212
TI  - 4849F, a new metabolite produced by the Streptomyces sp. 4849 as an inhibitor of
      IL-4 receptor.
AB  - A new compound named 4849F was isolated from the Streptomyces sp. 4849. The
      structure of 4849F was elucidated by spectroscopic analyses. The immobilized
      ligand-binding assay showed that 4849F can competitively inhibit the binding of
      IL-4 with IL-4 receptor in a dose dependent manner with an IC50 value of 6.7
      microM.

PMID- 17551213
TI  - The first hydroxylated archazolid from the myxobacterium Cystobacter violaceus:
      isolation, structural elucidation and V-ATPase inhibition.
AB  - The novel macrocyclic polyketide, 10-hydroxymethyl-archazolid-7-O-beta-D
      glucopyranoside (archazolid D), was obtained from the myxobacterium Cystobacter
      violaceus. The structure of this first hydroxylated archazolid was determined by
      spectroscopic analysis, in particular by HMBC, HMQC, and ROESY NMR
      investigations, and by degradation. This novel metabolite was evaluated for
      growth inhibition of murine connective tissue cells and V-ATPase inhibition in
      comparison to other known archazolids.

PMID- 17551214
TI  - A new cadinane sesquiterpene with significant anti-HIV-1 activity from the
      cultures of the basidiomycete Tyromyces chioneus.
AB  - A new cadinane sesquiterpene (4beta,14-dihydroxy-6alpha,7betaH-1(10)-cadinene, 1)
      was isolated from the cultures of the basidiomycete, Tyromyces chioneus. Its
      structure was established on the basis of spectral measurements (MS, IR, 1D and
      2D NMR experiments). 1 showed significant anti-HIV-1 activity with EC50=3.0
      microg/ml (SI=25.4).

PMID- 17551215
TI  - Antibacterial activity of allicin alone and in combination with beta-lactams
      against Staphylococcus spp. and Pseudomonas aeruginosa.
AB  - Allicin is one of the most effective compounds isolated from garlic showing
      antibacterial activity. Determination of MIC alone or in combination with
      cefazolin/oxacillin against Staphylococcus spp. or with cefoperazone against
      Pseudomonas aeruginosa showed that allicin alone did not have good antibacterial
      activity (MIC90>512 microg/ml) but it facilitated antibacterial activity of all
      three beta-lactams tested at subinhibitory concentrations. In the presence of 1/8
      to 1/2 the MIC of allicin, the MIC90 values of cefazolin, oxicillin, and
      cefoperazone were reduced by 4 approximately 128, 32 approximately 64, and 8
      approximately 16 fold, respectively. Thus, allicin-beta-lactam combinations offer
      promise of clinical utility especially if synergism is demonstrated by in vivo
      experimental studies.

PMID- 17551216
TI  - Vasopressor therapy using vasopressin prior to crystalloid resuscitation in
      irreversible hemorrhagic shock under isoflurane anesthesia in dogs.
AB  - In the present study, we tested the hypothesis that vasopressin administration
      prior to crystalloid resuscitation can be used to improve hemodynamic and oxygen
      delivery functions. Hemorrhagic shock was experimentally induced by maintaining
      mean arterial pressure at 60 mmHg for 30 min in sixteen healthy dogs weighing
      from 8 to 10.6 kg. Vasopressin was administered and then volume resuscitation was
      performed for the 6 dogs of V-C group, while vasopressin was administered at the
      end of volume resuscitation in the 5 dogs of C-V group. The control group (n=5)
      was administered 0.4 IU/kg of vasopressin after induction of shock without fluid
      resuscitation. In all groups, hemodynamic parameters were measured pre- and post
      hemorrhage and for 60 min after fluid resuscitation. The dogs in V-C group had
      substantially increased systolic arterial pressure (SAP) for 60 min and improved
      pulmonary capillary wedge pressure (PCWP), cardiac output (CO), oxygen delivery,
      and oxygen consumption indexes compared with C-V and control groups. Diastolic
      pressure and systemic vascular resistance was significantly lower in the V-C
      group than those in the C-V and control groups (P<0.05). In the V-C group, there
      was effective and rapid restoration of the SAP, CO, PCWP, and oxygen delivery
      parameters after treatment. This study indicates that vasopressin administration
      before crystalloid resuscitation is a more efficient way of improving hemodynamic
      and oxygen delivery functions in hemorrhagic shock in dogs.

PMID- 17551217
TI  - Indocyanine green angiography for examining the normal ocular fundus in dogs.
AB  - In dogs, a variety of diseases of the retina and choroid have been reported,
      either separately or concomitantly; however, the canine choroid is difficult to
      evaluate by veterinary techniques currently available. Indocyanine green (ICG)
      angiography is widely used in human ophthalmology, but has not been investigated
      for use in canine ophthalmology. The aim of this study was to apply a new
      approach to ICG angiography and compare the resulting angiograms with fluorescein
      (FLUO) angiograms of the ocular fundus in dogs. With a fundus camera equipped
      with an infrared-sensitive charged coupled device (CCD), we performed angiography
      on eight healthy beagles under inhalation anesthesia. ICG angiography enabled
      clear visualization of the choroidal vasculature, whereas FLUO angiography showed
      only the retinal vessels. At 8.4 +/- 3.6 sec after administration of ICG dye into
      the cephalic vein, the choroidal arteries could be seen extending radially from
      the optic disc, then the choroidal veins became apparent at 10.2 +/- 4.1 sec,
      coursing alongside the choroidal arteries. Gradual fading of the choroidal
      vessels began 13.2 +/- 2.2 min after the dye was administered, and overall
      diffuse fluorescence of the fundus appeared. Diffuse fluorescence of the fundus
      continued after the choroidal vessels and optic disc faded at about 58.3 +/- 5.3
      min from administration of the dye. In conclusion, ICG angiography provides clear
      resolution and is reliable and simple, thus offering promise as a diagnostic aid
      for clinical evaluation of the choroid in dogs.

PMID- 17551218
TI  - Detection of bovine torovirus in fecal specimens of calves with diarrhea in
      Japan.
AB  - The aim of this study was to determine the prevalence of bovine torovirus (BoTV)
      in bovine fecal samples and to determine whether a relationship exists between
      BoTV and diarrhea in Japan. Ninety-nine diarrheic and 114 normal fecal samples
      from calves in Hokkaido Prefecture and 38 diarrheic fecal samples from calves in
      10 other prefectures were examined by reverse transcription (RT)-PCR with primers
      designed in the spike (S) gene for the presence of BoTV. The specimens were also
      examined for the presence of other enteric pathogens, bovine rotavirus,
      coronavirus and Cryptosporidium spp. BoTV RNA was detected in 15 (15.2%) of the
      99 diarrheic samples from Hokkaido and in 9 (23.7%) of the 38 diarrheic samples
      from the other prefectures. The incidence of BoTV in control specimens was 7.0%.
      In 11 of the 15 BoTV-positive specimens from Hokkaido, BoTV was the only pathogen
      detected among those examined, and 11 BoTV-positive specimens were obtained from
      calves less than 2 weeks of age. Rotavirus was confirmed to be associated with
      calf diarrhea, but coronavirus and Cryptosporidium spp. were not. Nucleotide
      sequences of 17 different BoTV RT-PCR products were determined. Phylogenetic
      analysis based on the sequences revealed that Japanese BoTVs could be classified
      into at least two groups. This study showed that BoTV is a common virus in fecal
      specimens of calves with diarrhea in Japan and may be an important pathogen of
      cattle, principally in young calves less than 2 weeks of age.

PMID- 17551219
TI  - A rapid agglutination assay for canine brucellosis using antigen coated beads.
AB  - Brucella canis is the causative agent of canine brucellosis and facultative
      intracellular pathogen. The diagnosis of canine brucellosis is based on
      bacteriological examination and serological methods including agglutination and
      gel diffusion tests. In this study, crude antigens were extracted from B. canis
      using hot saline, coated on to latex beads and their usefulness in the
      serological diagnosis of canine brucellosis was examined. Mixing the antigen
      coated latex beads with the sera of dogs infected with B. canis produced clear
      agglutination, but this was not so for B. canis free dog sera. N-terminal amino
      acid sequence analysis of the crude hot saline extracts, showed that they
      contained copper-zinc superoxide dismutase, ribose ABC transporter and
      hypothetical protein of Brucella as antigens. A serological survey of canine
      serum samples conducted by means of an agglutination test using the antigen
      coated latex beads, showed that this method was more specific than the tube
      agglutination test using whole bacterial cell antigens. Although these results
      suggest that our method in which crude hot saline extracted antigens are coated
      on to latex beads would be useful in the serological diagnosis of canine
      brucellosis, we need further investigation using more serum samples to confirm
      the usefulness of our method.

PMID- 17551220
TI  - A novel culture method of canine peripheral blood lymphocytes with concanavalin a
      and recombinant human interleukin-2 for adoptive immunotherapy.
AB  - This study was designed to develop a novel culture method for the efficient
      proliferation of canine peripheral blood lymphocytes (cPBL) for adoptive
      immunotherapy. When cPBL were cultured in the presence of concanavalin A (Con A),
      proliferation of cPBL was induced and expression of interleukin-2 receptor (IL
      2R) which enables to respond to exogenously added IL-2 was upregulated. And then,
      when cPBL were cultured with recombinant human interleukin-2 (rhIL-2) in addition
      to Con A, proliferation was accelerated and increased to about 10-fold after 1
      week. The phenotypic analysis showed that the main population of the cultured
      cPBL was consisted of CD8+ positive lymphocytes. Among them, CD4+CD8+ double
      positive (DP) lymphocytes had significantly increased, and the ratio of CD4+
      single positive (SP) lymphocytes to CD8+ SP lymphocytes (CD4+SP/CD8+SP) was
      decreased as compared to before culturing. To evaluate the cytotoxic activity of
      cPBL cultured with Con A and rhIL-2, furthermore, cytotoxic assay was carried out
      against xenogeneic melanoma cell line (MeWo), which resulted in MHC-unrestricted
      cytokilling. These results suggest that the culture method of cPBL by the use of
      Con A and rhIL-2 may be useful for generating lymphokine activated killer cells,
      and also this may be beneficial for adoptive immunotherapy of tumor-bearing dogs.

PMID- 17551221
TI  - Genetic diversity of Trypanosoma evansi in buffalo based on internal transcribed
      spacer (ITS) regions.
AB  - The nucleotide sequences of 18S rDNA and internal transcribed spacer (ITS)
      regions were used for studying the relationships of Trypanosoma evansi isolate
      from a buffalo. The sequences were analyzed and compared to 18S rDNA and the ITS
      regions of the other Trypanosoma spp. Maximum likelihood phylogenetic trees were
      constructed using Leishmania major as the outgroup. The tree of 18S rDNA
      indicated that T. evansi (buffalo B18) isolate was closely related to those of
      Taiwan and T. brucei stock. The ITS tree showed the genetic diversity among 32
      clones of T. evansi (B18) within a single host. This data will be useful for
      epidemiological and dynamic studies for designing the rational control programs
      of the disease.

PMID- 17551222
TI  - Role of beta1 integrins in adhesion of canine mastocytoma cells to extracellular
      matrix proteins.
AB  - The interactions of tumor cells with the extracellular matrix (ECM) are a crucial
      step in invasion and metastasis. Integrins are adhesive molecules forming
      heterodimers with alpha and beta subunits that play a definitive role in these
      interactions. In this study, mastocytoma (mast cell tumor: MCT) cell-ECM
      interaction was investigated using 3 canine MCT cell lines: CM-MC (originating
      from cutaneous MCT), VI-MC (originating from intestinal MCT), and CoMS
      (originating from oral MCT). Flow cytometric analysis showed that all cells
      highly expressed the integrin beta1 and alpha1 through alpha5 subunits and that
      they moderately expressed the alpha6 subunit. In adhesion studies, CoMS weakly
      but spontaneously adhered to fibronectin (FN), which was enhanced by phorbol
      ester (TPA), while CM-MC and VI-MC required cell activation by TPA to adhere to
      FN. Anti-beta1 and alpha5 integrin antibodies strongly inhibited cell adhesion to
      FN in CM-MC and CoMS and moderately inhibited cell adhesion in VI-MC. Only VI-MC
      adhered to laminin (LN) under activation by TPA. Anti-beta1 integrin antibodies
      strongly inhibited cell adhesion to LN, but all anti-alpha integrin antibodies
      failed to inhibit cell adhesion to LN. No cells adhered to collagen types I and
      IV. Canine MCT cells from different origins expressed similar integrin patterns;
      however, there were some differences in adhesive behavior in response to various
      ECM proteins and activating stimuli.

PMID- 17551223
TI  - Ultrastructural study on the differentiation and the fate of M cells in follicle
      associated epithelium of rat Peyer's patch.
AB  - The differentiation process of immature microvillous epithelial cells to M cells
      and the fate of M cells in the follicle-associated epithelium (FAE) of the mucosa
      associated lymphoid tissues are still unclear. In this study, the differentiation
      process and the fate of M cells were clarified in rat Peyer's patches under a
      transmission electron microscope. Almost all immature epithelial cells were found
      to possess long, slender microvilli, which gradually shortened, thickened and
      dispersed as the immature epithelial cells migrated away from the crypt orifices.
      These morphological changes started in the centers and moved to the peripheries
      of the apical surfaces of epithelial cells, accompanied by the protrusion of
      apical cytoplasm out of the terminal web. During these changes, the bundles of
      microfilaments of microvilli never shortened, and both small vesicles in the
      apical cytoplasm and tiny invaginations of the apical membranes were found. The
      intraepithelial migrating cells gradually accumulated to form typical
      intraepithelial pockets. In all FAE, there was no morphological sign of cell
      death in M cells. The rearrangement of microfilament bundles, the reconstruction
      of microvilli and the disappearance of pockets resulted in the transformation of
      M cells into microvillous epithelial cells. These serial ultrastructural changes
      suggest that M cells are a temporal and transitional cell type caused by the
      active engulfment of luminal substances and that when the engulfment ceases, the
      M cells transform into mature microvillous epithelial cells.

PMID- 17551224
TI  - Induction of proinflammatory cytokines and caspase-1 by leptin in
      monocyte/macrophages from holstein cows.
AB  - The proliferation of peripheral blood mononuclear cells (PBMC) containing both
      monocyte/macrophages and T lymphocytes increased after treatment with T-cell
      mitogen (concanavalin A: Con A). PBMC treated with either leptin alone or
      combination of leptin and ConA showed enhanced proliferative activity by 10-40%,
      compared with those treated with ConA alone. In contrast, isolated T lymphocytes
      treated with leptin and ConA showed lowered proliferative activity than the ConA
      treated alone, indicating that leptin induced production of some cytokines from
      monocyte/macrophages, that subsequently resulted in enhancement of T lymphocytes
      proliferation in PBMC. Among the cytokines examined, monocyte/monocytes
      constitutively expressed interleukin (IL)-1beta, IL-12p35, IL-18 mRNA, and
      faintly expressed tumor necrosis factor (TNF)-alpha and IL-12p40 mRNA. Leptin
      treatment augmented the monocyte/macrophages mRNA expression of only TNF-alpha
      and IL-12p40 to comparable levels of cells treated with lipopolysaccharide (LPS).
      However, leptin treatment increased monocyte/macrophages production of IL-1beta
      as well as TNF-alpha, and induced the mRNA expression of caspase-1, which is
      shown to mediate the conversion of latent pro-IL-1beta and pro-IL-18 to active
      forms. These results suggest that leptin directly acts on monocyte/macrophages to
      produce factors that induce T lymphocytes proliferation such as IL-12p35/p40
      complex through IL-12p40 induction and IL-1beta/IL-18 production through caspase
      1 induction.

PMID- 17551225
TI  - Genetic and pathobiological characterization of bovine viral diarrhea viruses
      recently isolated from cattle in Japan.
AB  - The 475 strains of bovine viral diarrhea virus (BVDV) isolated from cattle in 12
      prefectures of Japan in the last 7 years were phylogenetically classified as BVDV
      1 or BVDV-2 on the basis of the nucleotide sequence of the 5'-untranslated
      region. BVDV-1 strains were further subtyped as 1a (101 strains), 1b (163), 1c
      (128), 1j (3), and So CP/75-like (1), and all of the 79 BVDV-2 strains belonged
      to subtype 2a. These 2a BVDVs contain two isolates that had high nucleotide
      identities with those of highly pathogenic BVDV-2 strains reported in North
      America (Pellerin et al., 1994). However, acute infection with severe mortality
      like North American outbreak was not observed and most of the present BVDV-2
      strains were isolated from persistently infected (PI) cattle showing mild or no
      clinical sign. Moreover, it was revealed that 61.5% of the 39 PI cattle with
      cytopathogenic BVDVs did not show typical mucosal disease and 54.6% of the 405 PI
      animals only with non-cytopathogenic BVDVs were apparently healthy. The present
      results indicate that the prevention of the infection with an appropriate vaccine
      and active surveillance covering healthy cattle are required for the control of
      BVD.

PMID- 17551226
TI  - The evaluation of autonomic nervous system activation during learning in rhesus
      macaques with the analysis of the heart rate variability.
AB  - The aims of this study were to measure the activity of the autonomic nervous
      system using heart rate variability (HRV) during learning tasks and to clarify
      the relationship between learning to overcome a difficult situation and the
      autonomic nervous system in monkeys. Two young male monkeys (Macaca mulatta) were
      given simple discrimination learning tasks (DL) and delayed matching to samples
      tasks (DMTS); Holter-type electrocardiography was done, and HRV was measured. We
      defined the frequency bands of HRV in rhesus macaques; the low frequency (LF) was
      0.01-0.15 Hz, and the high frequency (HF) was 0.15-0.50 Hz. Based on these
      frequency bands, the LF/HF ratios during learning tasks were analyzed, and a
      significant increase in the ratio was found during the tasks. The variances in
      the HF differed between the DL and DMTS tasks; during DMTS tasks, HF variances
      had a tendency to increase. Our results indicate that increased sympathetic
      activity accompanied learning and suggest that the parasympathetic nervous system
      plays a key role during learning, particularly when difficult tasks are being
      learned.

PMID- 17551227
TI  - Distribution of inclusion bodies in tissues from 100 dogs infected with canine
      distemper virus.
AB  - One hundred dogs that were positive for canine distemper virus antigen and
      inclusion bodies in the tonsils were examined for the distribution of inclusion
      bodies in various tissues. Inclusion bodies were found in the lungs (70 dogs),
      brains (20 dogs), urinary bladders (73 dogs), stomachs (78 dogs), spleens (77
      dogs), and lymph nodes (81 dogs) of the dogs. Based on these results, the tonsils
      may be the most suitable tissue for detection of inclusion bodies in canine
      distemper.

PMID- 17551228
TI  - Pulmonary vascular proliferation and lungworm (Stenurus ovatus) in a bottlenose
      dolphin (Tursiops turncatus).
AB  - A female adult bottlenose dolphin suddenly died at 17 days after the capture.
      Macroscopically, severe pulmonary congestive edema was found. Histopathology
      revealed many lungworms in the bronchioli and the worms were identified as
      Stenurus ovatus. Variously sized vessels proliferated around the lesioned
      bronchioli. Based on these findings, chronic bronchopneumonia due to the lungworm
      was diagnosed and vascular proliferation was similar to angiomatosis recently
      reported in Atlantic bottlenose dolphin.

PMID- 17551229
TI  - Stimulation of mucosal and systemic antibody responses against recombinant
      transferrin-binding protein B of Actinobacillus pleuropneumoniae with chitosan
      after tracheal administration in piglets.
AB  - This study evaluated the suitability of using a chitosan formulation as an
      adjuvant to enhance both the mucosal and systemic immune responses against
      recombinant transferrin-binding protein B (rTbp B) of Actinobacillus
      pleuropneumoniae via direct tracheal administration. The chitosan formulation was
      found to enhance mucosal immune response, as measured by the secretory IgA level
      in lung lavage fluid and lung homogenate extracts, and systemic immune response,
      as measured by the serum IgG level.

PMID- 17551230
TI  - The first outbreak of camelpox in Syria.
AB  - In this study we report the first outbreak of camelpox in two provinces in Syria.
      Clinical symptoms started with fever, salivation and general exanthema. The main
      features were facial and legs oedema, pustules on the mucosa of the lips and a
      high rate of abortion. Lesions may also occur on the whole body including scrotum
      and udder. Specimens were investigated by electron microscopy, virus isolation in
      cell culture and embryonated eggs and by immunohistochemistry. The causative
      agent was identified as camelpox virus by polymerase chain reaction and
      sequencing of the hemagglutinin gene.

PMID- 17551231
TI  - Phylogenetic relationships of rodent pinworms (genus Syphacia) in Japan inferred
      from mitochondrial CO1 gene sequences.
AB  - Species of the genus Syphacia are considered to have generally co-evolved with
      their rodent hosts. This study determined partial sequences of the CO1 gene from
      several species in the genus Syphacia and discuss the relationships between
      pinworms and their hosts. Syphacia montana, which parasitizes Microtinae, was
      closely related to S. frederici and S. obvelata, which parasitize Murinae.
      Although both S. obvelata and S. ohtaorum parasitize rodents in the genus Mus,
      these two species were not found to be closely related to each other. Syphacia
      frederici, S. emileromani and S. agraria are all pinworms of the Apodemus
      species, but genetic affiliation between these three species was not indicated.
      These facts suggest that the co-evolutionary relationship between species of the
      genus Syphacia and their host rodents may not so strict and host switching has
      probably occurred during the course of evolution.

PMID- 17551232
TI  - Relationship between depression score and acid-base status in Japanese Black
      calves with diarrhea.
AB  - We evaluated the relationship between depression score and acid-base status in 84
      purebred and crossbred Japanese Black calves. The bicarbonate (p<0.001) and base
      excess concentrations (p<0.001) were significantly and negatively correlated with
      the depression scores of the calves. The proposed diagnostic cutoff point for a
      depression score that indicates severe metabolic acidosis (BE < -10 mM) is 6.5
      based on analysis of the ROC curve. The sensitivity and specificity were 88.4%
      and 81.2%, respectively. The depression scoring system is a useful tool for
      evaluation of the acid-base status of purebred and crossbred Japanese Black
      calves. In addition, a depression score of 6.5 suggests severe metabolic acidosis
      and that intravenous infusion of sodium bicarbonate solution is necessary.

PMID- 17551233
TI  - Harlequin ichthyosis in a HanWoo calf.
AB  - Ichthyosis (fish scale disease) is a rare hereditary disease and characterized by
      excessive cutaneous scale formation. A male HanWoo calf born by natural service
      was found with fissures and thickened, scaly, cutaneous plates covering over 90%
      of its body. Histopathological feature was excess compact orthokeratotic
      hyperkeratosis involving surface of the epidermis and follicular epithelia. The
      calf had small malformed ears, ectropion, eclabium and an abnormal nose. Gross
      and histopathologic findings in calf were consistent with those of harlequin
      ichthyosis, and it was the first observed harlequin ichthyosis in HanWoo cattle.

PMID- 17551234
TI  - In vitro glucuronidation of estradiol-17beta by microsomes prepared using liver
      biopsy specimens from dairy cows.
AB  - Increased hepatic metabolism of estradiol may cause weakened estrous behavior in
      lactating dairy cows, but this hypothesis must be examined further, especially
      through diachronic study of the hepatic estradiol-17beta glucuronidation activity
      of uridine diphosphate (UDP)-glucuronosyltransferases. Therefore, in order to
      develop a new tool for this purpose, we attempted to conduct biopsy of the livers
      of dairy cows with the aid of ultrasonography and to measure the UDP
      glucuronosyltransferase activities of microsomes of the specimens using in vitro
      glucuronidation followed by HPLC analysis. We were able to measure the activities
      of the microsomes prepared from the liver biopsy, and the results seemed
      reliable. Therefore, this method may become a new tool in clinical studies to
      detect estradiol-17beta glucuronidation activity.

PMID- 17551235
TI  - Changes in the plasma testosterone level and testicular superoxide dismutase
      activity of 5 azoospermic beagles after GnRH analogue injections.
AB  - The peripheral blood plasma testosterone (T) levels and superoxide dismutase
      (SOD) activity were measured in 5 azoospermic (AZ-) beagles. The mean values in
      the AZ-dogs were significantly lower than in 7 control beagles (P<0.001).
      Subcutaneous injections of 1 mug/kg GnRH analogue three times weekly in the AZ
      dogs induced significant increases in mean T level and SOD activity (P<0.05) and
      improvement in spermatogenesis. Thus, spermatogenic function in the dog appears
      to be maintained by T and normal SOD activity in the testis.

PMID- 17551236
TI  - A Possible treatment strategy and clinical factors to estimate the treatment
      response in Bebesia gibsoni infection.
AB  - The effectiveness of combination therapy using clindamycin, metronidazole and
      doxycycline against canine babesiosis, and the usefulness of platelet count and
      the plasma C-reactive protein (CRP) concentration as an estimation factor for
      treatment, were evaluated in four dogs experimentally infected with Babesia
      gibsoni. The combination therapy successfully eliminated B. gibsoni in peripheral
      blood in 3 of 4 dogs, however the remaining dog showed obvious uncontrolled
      relapse after a temporary recovery. In addition, it was shown that CRP levels
      decreased in an inverse relationship to the recovery of packed cell volume and
      therefore CRP levels could be used as an optional clinical marker to estimate the
      response to treatment.

PMID- 17551237
TI  - Ovarian activity and pregnancy in the Siberian tiger, Panthera tigris altaica,
      assessed by fecal gonadal steroid hormones analyses.
AB  - Feces were collected from two female and one male Siberian tigers, Panthera
      tigris altaica. Steroid hormones were extracted from lyophilized feces and
      quantified by enzyme immunoassay. The fecal contents of estradiol-17beta (E(2))
      and testosterone in the females and male, respectively, changed markedly
      throughout the year. The fecal E(2) contents of females Nos. 179 and 238
      increased at 26.4 +/- 8.0 and 28.0 +/- 14.2 day intervals, respectively. However,
      the fecal contents of progesterone (P(4)) in the female kept alone did not
      change. In contrast, the other female, which was kept with a male, had increased
      fecal P(4) contents after copulation. The fecal progesterone levels of the
      pregnant female remained high during her 106-day pregnancy.

PMID- 17551238
TI  - Molecular characterization of the equine herpesvirus 1 strains RacL11 and
      Kentucky D.
AB  - The pathogenicities of RacL11 and Kentucky D strains of equine herpesvirus 1 in
      the hamster infection model are different from those of Ab4p and the Japanese
      isolates. Virus genome restriction fragment length polymorphism analysis and
      sequence comparison of an intergenic region, glycoproteins and tegument genes
      showed higher conservation but with some strain-specific differences. These
      results indicate that point nucleotide differences in RacL11 and Kentucky D might
      be responsible for their pathogenicity in rodent models.

PMID- 17551239
TI  - Effects of Atipamezole and Naloxone on Electroencephalographic Spectral Edge
      Frequency 95 in Dogs Sedated by Acupuncture at GV20 and Yintang Point.
AB  - The purpose of this study was to evaluate the antagonism of acupuncture-induced
      sedation by electroencephalographic spectral edge frequency (SEF) 95 in 10
      healthy intact male Miniature Schnauzer dogs (4.2-6.1kg; 2-3 years old) without
      neurological disorder. The GV20 and Yintang acupoints were administered for 20
      min. While the dogs were conscious, SEF 95 baseline values were recorded at 2-min
      intervals for 4 min. Then acupuncture was administered at the GV20 and Yintang
      acupoints. During the acupuncture procedure, the SEF 95 values were recorded at 2
      min intervals for 10 min. Subsequently, antagonist drugs, naloxone and
      atipamezole, were administered through the cephalic vein. The SEF 95 values were
      then measured again at 2-min intervals for 10 min. Those values were found to be
      significantly increased after administration of atipamezole in dogs sedated by
      acupuncture at the GV20 and Yintang acupoints (p<0.05). However, the SEF 95
      values in the naloxone groups did not show any significant changes before and
      after administration of the antagonist. It was concluded that sedation induced by
      acupuncture at the GV20 and Yintang acupoints might be partially associated with
      the alpha(2)-adrenergic system.

PMID- 17551240
TI  - Excess tyrosine stimulates eumelanin and pheomelanin synthesis in cultured slaty
      melanocytes from neonatal mouse epidermis.
AB  - The mouse slaty (Dct(slt)) mutation is known to reduce the activity of dopachrome
      tautomerase (DCT). The reduced DCT activity inhibits melanosome maturation and
      reduces the melanin content in the skin, hair and eyes. It is not known whether
      eumelanin and pheomelanin synthesis in slaty melanocytes is modulated by
      melanogenic factors. In this study, to address this point, epidermal melanocytes
      derived from 0.5-, 3.5- and 7.5-day-old wild-type mice (Dct(+)/Dct(+) at the
      slaty locus) and from congenic mice mutant (Dct(slt) /Dct(slt) at that locus)
      were cultured in serum-free primary culture with or without additional L-tyrosine
      (Tyr). The content of melanin was measured by high-performance liquid
      chromatography in the cultured melanocytes as well as culture supernatants in
      serum-free primary culture. L-Tyr was found to increase the content of
      pheomelanin in addition to eumelanin in cultured slaty melanocytes and cuture
      supernatants at all ages tested. The eumelanin and pheomelanin contents in
      culture supernatants were greater than in cultured melanocytes. The eumelanin and
      pheomelanin contents in culture supernatants from 7.5-day-old slaty melanocytes
      in the presence of L-Tyr were greater than those from wild-type melanocytes.
      These results suggest that the inhibition of eumelanin synthesis by the slaty
      mutation can be partly restored by the addition of excess L-Tyr. Eumelanin and
      pheomelanin may accumulate with difficulty in slaty melanocytes and be easily
      released from them during skin development. L-Tyr may stimulate this release.

PMID- 17551241
TI  - Population subdivision of the tri-spine horseshoe crab, Tachypleus tridentatus,
      in Taiwan Strait.
AB  - The genetic structure of the Asian tri-spine horseshoe crab, Tachypleus
      tridentatus, was investigated in three populations of Taiwan Strait using
      mitochondrial (mt) AT-rich region DNA sequences. We examined 23 individuals from
      Kinmen, an island located on the western side of Taiwan Strait, and 12 each from
      Tiexianwei and Dongwei near Magong Island in the Penghu Archipelago, in the
      middle of Taiwan Strait. DNA sequence analysis of 369 base pairs (bp) of the mt
      AT-rich region revealed 10 haplotypes among the 47 individuals, with a mean
      haplotypic diversity (h) of 0.626+/-0.075 and nucleotide diversity (pi) of
      0.0039+/-0.00055. Pairwise F-statistics (F(ST)) revealed significantly high gene
      flow between Kinmen and Dongwei (F(ST)=-0.0351, p>0.05, N(e)m=infinity), but
      marked population subdivision and restricted gene flow between Kinmen and
      Tiexianwei (F(ST)=0.1382, p<0.05, N(e)m=3.1176). Between populations at Magong
      Island, gene flow was moderate (F(ST)=0.0634, p>0.05, N(e)m=7.3913). Mismatch
      distribution analysis indicated that the relatively low haplotype and nucleotide
      diversity observed in the Tiexianwei T. tridentatus population can be attributed
      to a recent bottleneck, probably due to isolation of Tiexianwei in semi-closed
      Magong Bay that prevents gene flow from neighboring populations.

PMID- 17551242
TI  - Environmental and seasonal variation in the diet of Elachistocleis bicolor
      (Guerin-Meneville 1838) (Anura: Microhylidae) from northern Uruguay.
AB  - We studied the diet of Elachistocleis bicolor captured in pine, eucalypt, and
      unmodified environments in Uruguay. Comparisons between seasons (active,
      inactive) and among three environments (pine, eucalypt, unmodified), were made
      using rarefaction analyses, importance indices, and non-parametric tests.
      Elachistocleis bicolor has a specialized diet composed mainly of Pheidole and
      Solenopsis ants and termites. The diet of E. bicolor includes a high number of
      prey per individual, suggesting active search as a foraging strategy. The
      consumption of myrmicine ants (i.e., Solenopsis) represents a source for
      potential toxic skin secretions that in E. bicolor may be used to avoid being
      attacked in the ant nests used for shelter during aestivation, as occurs in the
      microhylid Phrynomantis microps. Diets in forested environments were richer in
      both periods, which may reflect the colonization of opportunistic ant species in
      these environments. Ants were more important in the eucalyptus plantations,
      particularly in the inactive period, whereas termites were more important in the
      pine plantations mainly in the inactive period. These environmental and seasonal
      differences in diet are consistent with the temperature and humidity tolerances
      of ants and termites, which are the main prey of E. bicolor.

PMID- 17551243
TI  - Effects of bilateral and unilateral eyestalk ablation on vitellogenin synthesis
      in immature female kuruma prawns, Marsupenaeus japonicus.
AB  - In penaeid shrimp species, vitellogenin (VTG) synthesis in the ovary and
      hepatopancreas is under the inhibitory regulation of a neuroendocrine system, the
      X-organ/sinus gland complex in the paired eyestalks, and eyestalk ablation
      (removal of the X-organ/sinus gland complex) is widely used for inducing ovarian
      development. However, the difference in effects of bilateral and unilateral
      ablation on VTG gene expression has not been clarified so far. In the present
      study, VTG synthesis was monitored over a 16-day period after ablation and
      compared between replicates of immature female kuruma prawns, Marsupenaeus
      (Penaeus) japonicus, that had been bilaterally or unilaterally ablated and
      control specimens. After bilateral ablation, ovarian development was induced, and
      the ovarian weight, hemolymph VTG levels, and VTG mRNA levels in the ovary
      increased significantly. Significant VTG mRNA increase was detected 12 h after
      bilateral ablation. In contrast, after unilateral ablation, ovarian development
      was not induced, and the ovarian weight, hemolymph VTG levels, and VTG mRNA
      levels in the ovary did not change significantly from the control. These results
      indicate that in immature female prawns, unilateral ablation does not induce VTG
      gene expression, whereas bilateral ablation induces rapid VTG gene expression
      (<12 h). The ineffectiveness of unilateral ablation suggests that the remaining X
      organ/sinus gland complex in the unilaterally ablated female prawns may secrete
      sufficient VIH to suppress VTG synthesis.

PMID- 17551244
TI  - Alternative leader-exon usage in mouse IGF-I mRNA variants: class 1 and class 2
      IGF-I mRNAs.
AB  - The mouse IGF-I gene contains six exons, and exon 1 and exon 2 gene are
      considered to be leader exons. The regulatory mechanism of alternative usage of
      the leader exons is unclear in mice. The present study was aimed at clarifying
      changes in class 1 (derived from exon 1) and class 2 (derived from exon 2) IGF-I
      mRNA expression in mice under various conditions. Both class 1 and class 2 IGF-I
      mRNAs were expressed in the mouse uterus, liver and kidney, and class 1 IGF-I
      mRNA was the major transcript in all organs studied. In the uterus, both class 1
      and class 2 IGF-I mRNA expression changed markedly during the estrous cycle, with
      the highest level at proestrus, but in the liver and kidney there were no
      significant changes in IGF-I mRNA expression during the estrous cycle. Estrogen
      treatment increased both class 1 and class 2 IGF-I mRNA levels in the uterus of
      ovariectomized mice, but class 1 mRNA expression increased more in response to
      estrogen treatment than class 2 mRNA expression. These findings suggest that
      estrogen stimulates IGF-I gene expression in uterine cells, and that a promoter
      involved in transcription of class 1 IGF-I mRNA is more responsive to estrogen.
      In conclusion, the present study revealed that two leader exons of mouse IGF-I
      gene are used in the uterus, liver and kidney. IGF-I mRNA levels of both classes
      changed during the estrous cycle in the uterus, but not in the liver or kidney.
      Estrogen increased IGF-I mRNA levels of both classes in the uterus.

PMID- 17551245
TI  - Identification of a novel yolk protein in the hermatypic coral Galaxea
      fascicularis.
AB  - The reef-building (or hermatypic) coral Galaxea fascicularis (Anthozoa,
      Hexacorallia, Scleractinia) has an annual reproductive cycle. Females of G.
      fascicularis release packages (or ;bundles') of eggs for external fertilization,
      whereas male individuals form bundles consisting of sperm and infertile ;pseudo
      eggs' that are thought to confer buoyancy to the male bundle. In the egg of G.
      fascicularis, four proteins (GfEP-1 to 4) were found to be stored in high
      abundance, and three of them (GfEP-1, 2 and 3) are generated by processing of a
      vitellogenin (Vg)-like precursor. In the present study, a cDNA encoding GfEP-4
      was cloned and its sequence determined (GenBank/EMBL/DDBJ accession no.
      AB259859). The amino acid sequence of this protein does not exhibit similarity to
      known proteins, including Vgs or other yolk proteins found in some invertebrates.
      The expression of GfEP-4 mRNA was observed in females, and also in the majority
      of males examined, although expression levels were lower than in females. The
      GfEP-4 protein was detected in pseudo-eggs, where its concentration was 20-100
      times lower than in eggs. In contrast, GfEP-1, 2 and 3 were not detected in
      pseudo-eggs. A protein (28 kDa) which cross-reacted with anti-GfEP-4 antibodies
      was detected in eggs of the coral Montipora digitata, suggesting the possibility
      that homologs of this protein are present in the eggs of other scleractinian
      corals.

PMID- 17551246
TI  - Autopodial development in the sea turtles Chelonia mydas and Caretta caretta.
AB  - The manus and pes were studied using whole-mount and histological preparations of
      ontogenetic series of Chelonia mydas and Caretta caretta. Patterns of
      connectivity and sequences of chondrification events are similar to those
      reported for other turtle species, with respect to both the primary axis and the
      digital arch. There is no evidence of anterior condensations in the region distal
      to the radius and the tibia, supporting the hypothesis that the radiale and
      tibiale are absent in turtles. The three middle metacarpals are the first
      elements to start ossification in the manus of C. mydas, while ossification has
      not started in the pes. In the hatchling of C. mydas, most carpals have started
      ossification, whereas tarsals are mostly still cartilaginous. In C. caretta, the
      first carpals to ossify are the ulnare and intermedium, followed by the pisiform.
      Among metatarsals, the fifth hooked metatarsal is the last one to start
      ossification. The fibulare and intermedium fuse early in chondrogenesis, later
      becoming the astragalocalcaneum. Ossification in the carpals of C. caretta starts
      while tarsals are still cartilaginous. The derived autopodial proportions in each
      autopodium of adults are laid out at the condensation stage, and features that
      were present in basal turtles are absent at all stages examined (developmental
      penetrance). In contrast to this, conservatism is expressed in the presence of
      similar patterns of connectivity during early chondrogenesis, and in the
      development of overall proportions of the manus versus pes. As in adult anatomy,
      the development of the autopodium of marine turtles is a mosaic of derived and
      plesiomorphic features.

PMID- 17551247
TI  - Genetic identification and molecular phylogeny of Pseudodiaptomus species
      (Calanoida, Pseudodiaptomidae) in Korean waters.
AB  - Five species of the genus Pseudodiaptomus, P. inopinus, P. poplesia, P. marinus,
      P. nihonkaiensis, and P. sp. occur in Korea nearshore waters. Although the four
      species except for P. sp. have been classified into Lobus and Ramosus groups, two
      for each group, based on morphological characters, this classification had yet to
      be confirmed by molecular characters. Here, we determined molecular characters
      and phylogenetic relationships of the five species in order to evaluate the
      morphology-based groupings and the species identifications. For this, a 625-bp
      DNA region of the mitochondrial gene cytochrome oxidase subunit I (mtCOI) was
      sequenced and compared among the species. Intraspecific variation of the
      sequences is less than 0.6%, while interspecific variation ranges from 17.6
      26.7%, indicating every species, including P. sp., is a genetically distinct,
      valid species. Phylogenetic trees of the mtCOI DNA reveal that the Lobus-group
      species including P. inopinus and P. poplesia form a well-supported clade and
      that P. sp. belongs to this group. On the other hand, the Ramosus group clade
      consisting of P. marinus and P. nihonkaiensis is not well supported by bootstrap
      analyses, suggesting that further evaluation of the validity of this group
      assignment is needed.

PMID- 17551248
TI  - Developmental changes in heart photosensitivity of the isopod crustacean Ligia
      exotica.
AB  - During juvenile development, the cardiac pacemaker of the isopod crustacean Ligia
      exotica is transferred from the myocardium to the cardiac ganglion of the
      neurogenic heart. In adult, light stimulus decreases the beat frequency of the
      heart. To elucidate developmental changes in the photosensitivity of the juvenile
      Ligia heart, we examined the effect of a light stimulus on the semi-isolated
      heart of juveniles at various developmental stages by the recording membrane
      potential of the myocardium. We also examined the effect of hyperpolarizing
      current injection into the myocardium, because this causes different effects on
      the beat frequency between myogenic and neurogenic hearts. In newly hatched
      juveniles, beat frequency decreased upon current injection but exhibited no
      response to white light. In contrast, 10 days after hatching, beat frequency did
      not change upon current injection, but decreased in response to white light. The
      heart photoresponse of juveniles was reversibly eliminated by application of
      tetrodotoxin, which changes the heartbeat from neurogenic to myogenic by
      suppressing cardiac ganglion activity. The proportion of juveniles exhibiting a
      heart photoresponse increased gradually up to 100% during the period between 3
      and 10 days after hatching. The results suggest that the heart photoresponse of
      L. exotica appears in association with transfer of the cardiac pacemaker from the
      myocardium to the cardiac ganglion during juvenile development.

PMID- 17551250
TI  - Retraction. Regulation of FoxO1 transcription factor by nitric oxide and cyclic
      GMP in cultured rat granulosa cells.

PMID- 17551249
TI  - Possible self-fertilization in the brooding coral Acropora (Isopora)
      brueggemanni.
AB  - We examined gametogenesis and the periodicity of planula release in the brooding
      coral Acropora (Isopora) brueggemanni (Brook, 1893) on Akajima Island, Okinawa,
      Japan. We captured the moment when A. brueggemanni would be in the process of
      self-fertilization. Whole colonies of this species were cultured separately or
      together with other colonies in plastic containers. We observed no apparent
      periodicity of planula release in the collected colonies. A few planulae were
      released intermittently during the observation period, regardless of whether the
      colonies were cultured individually or with other colonies. Serial paraffin
      sections of A. brueggemanni showed follicle-like cells surrounding the oocyte
      during vitellogenesis. In September and October, some spermaries looked half
      broken and some ova were surrounded by sperm or spermaries instead of follicle
      like cells. Such ova were heart-shaped and may have been cells at the first
      cleavage stage. These observations suggest that the migration of spermaries
      and/or oocytes resulted in the close proximity of oocytes and sperm, which would
      allow self-fertilization. This possibility, together with the production of
      planula larvae by isolated colonies, suggests that this brooding coral engages in
      self-fertilization.

PMID- 17551251
TI  - Pulmonary alterations during BEP? Always be aware of BIP.

PMID- 17551252
TI  - Measurement of DPD and TS transcripts aimed to predict clinical benefit from
      fluoropyrimidines: confirmation of the trend in Russian colorectal cancer series
      and caution regarding the gene referees.
AB  - BACKGROUND: Measurement of intratumoral expression of dihydropyrimidine
      dehydrogenase (DPD) and thymidylate synthase (TS) may have some value in
      predicting the response to fluoropyrimidine-containing therapy. PATIENTS AND
      METHODS: We attempted to validate this association in a series of Russian
      metastatic colorectal cancer cases. While replicating already published
      protocols, we unexpectedly found that the use of commonly utilized gene referees,
      glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and beta-actin, may lead to
      artifacts due to pseudogene-driven amplification from the genomic DNA template.
      We have developed a real-time PCR protocol which amplifies short PCR fragments,
      thus allowing efficient analysis of archival formalin-fixed paraffin-embedded
      tumor samples, and relies on succinate dehydrogenase (SDHA) as a gene referee,
      therefore avoiding amplification from genomic DNA. RESULTS: Low content of DPD
      transcripts was observed in 13/20 (65%) patients with disease control (tumor
      response or disease stabilization) as compared to only 3/9 (33%) subjects with
      progressive disease (p = 0.11). Despite the low number of patients, this
      association reached the level of statistical significance when similar analysis
      was done for TS expression (11/20 (55%) vs. 1/9 (11%); p = 0.03). CONCLUSIONS:
      Our data confirm that low DPD and TS expressors have higher chances of success of
      fluoropyrimidine-containing regimens.

PMID- 17551253
TI  - Quantitative and semiquantitative evaluation of erythropoietin-induced bone
      marrow signal changes in lumbar spine MRI in patients with tumor anemia.
AB  - BACKGROUND: The topic of this article is the quantitative and semiquantitative
      assessment of bone marrow signal alteration in magnetic resonance imaging (MRI)
      of the lumbar spine in patients with tumor anemia during therapy with epoietin
      beta or placebo. PATIENTS AND METHODS: We examined 32 patients with head or neck
      cancer (16 epoietin beta, 16 placebo) during radiotherapy in a double-blind
      multicenter trial. During radiotherapy, the patients underwent epoietin beta
      therapy for 7-9 weeks. Lumbar spine measurements using T1-w SE, OPP and Turbo-
      STIR were taken prior to the first epoietin beta or placebo therapy, after the
      acquired hemoglobin level had been reached, and after the final radiotherapy. The
      semiquantitative assessment was made blinded by 2 independent radiologists.
      RESULTS: We found significant differences between both groups. The first MRI
      showed normal marrow signals. The second MRI revealed a quantified decrease in
      bone marrow signal in T1-w SE (p < 0.018) and an increase in OPP (p < 0.01) and
      Turbo-TIR (p < 0.048) sequences. At the third MR imaging, quantified relative
      marrow signals returned to baseline level in all sequences. Semiquantitative
      assessment confirmed these results. CONCLUSION: In both analyses, lumbar spine
      MRI demonstrates significant bone marrow changes in T1-w SE, OPP and Turbo-STIR
      sequences during epoietin beta therapy.

PMID- 17551254
TI  - Reliable identification of small cell lung cancer in cytological specimens by
      immunocytology.
AB  - BACKGROUND: A reliable diagnosis of small cell lung cancers (SCLC) is of high
      clinical relevance. We investigated whether immunocytology substantially improves
      the diagnostic accuracy of conventional cytology in diagnosing SCLC. PATIENTS AND
      METHODS: 162 carcinomatous specimens clinically suspected to originate from
      pulmonary neoplasms were investigated by cytology and immunocytology.
      Immunocytology was performed on smears using HEA125 and pancytokeratin antibodies
      as epithelial markers and MOC-1 as SCLC probe. RESULTS: As histologically
      clarified, 114 specimens corresponded to pulmonary neoplasms (SCLC = 51; non
      small cell lung cancer: NSCLC = 59; mixed SCLC/NSCLC = 2; carcinoid = 2), 48 to
      nonpulmonary adenocarcinomas. By conventional cytology tumor cells were clearly
      detected in 93 (57.4%) and suspected in another 43 (26.5%) cases (83.9% overall
      sensitivity). Considering SCLC samples, tumor cells were diagnosed or suspected
      in 36 (70.5%), not identified in 10 (19.6%), and misdiagnosed as hematological
      malignancy in 5 cases. Only 2 specimens were accurately diagnosed as SCLC. Using
      the epithelial antibodies all samples were identified as carcinomatous. MOC-1
      stained all but one SCLC, both SCLC/NSCLC, and both carcinoids. One SCLC brush
      smear was MOC-1 negative, containing only squamous epithelium. 3 pulmonary
      adenocarcinomas stained falsely positive, all nonpulmonary carcinomas MOC-1
      negative. CONCLUSION: Immunocytology substantially improves the diagnostic
      accuracy of cytology in diagnosing SCLC with a diagnostic sensitivity of 98% and
      specificity of 97%.

PMID- 17551255
TI  - BRCA1 germline mutation in a woman with metaplastic squamous cell breast cancer.
AB  - BACKGROUND: Breast cancers arising in women with germline BRCA1 mutations are
      most likely to be estrogen receptor (ER), progesterone receptor (PR), and
      HER2/neu negative (so-called triple negative or basal-like breast cancers).
      Metaplastic carcinoma with pure squamous differentiation is a very rare
      histological subtype (0.1% of all breast cancers) and is usually ER, PR, and
      HER2/neu negative by immunohistochemistry. A BRCA1 germline mutation in squamous
      cell breast cancer has never been reported. CASE REPORT: A 25-year-old woman was
      diagnosed with squamous cell cancer of the breast. Three years later, she
      developed contralateral breast cancer, also of the squamous cell subtype. Both
      tumors were triple negative. Because of the patient's history and her strong
      family history, genetic testing was recommended. The patient was found to be
      carrier of a BRCA1 germline mutation. CONCLUSION: We report, to our knowledge,
      the first case of a BRCA1 mutation in a woman with metaplastic squamous cell
      breast cancer.

PMID- 17551256
TI  - Increased pulmonary FDG uptake in bleomycin-associated pneumonitis.
AB  - BACKGROUND: Bleomycin is an antineoplastic agent that is mainly used in
      combination regimens. Dose-limiting toxicity is the bleomycin-induced pneumonitis
      (BIP) that can be diagnosed by clinical and radiological findings. The early
      diagnosis of BIP is often challenging. CASE REPORT: We report the occurrence of a
      diffuse pulmonary increase of FDG uptake in the FDG-PET scan in association with
      suspected BIP in a patient treated for relapsed seminoma. A retroperitoneal
      relapse was treated with a combination chemotherapy containing cisplatin,
      etoposide, and bleomycin. After 3 cycles of this regimen the patient developed
      mild clinical signs of early BIP. A following FDG-PET in order to evaluate
      treatment response showed a diffuse increased FDG uptake of the right lung. The
      subsequent HRCT revealed pathological findings consistent with BIP. After
      cessation of bleomycin and a systemic steroid trial a prompt normalization of the
      abnormal radiological and clinical findings occurred together with a
      disappearance of the increased pulmonary FDG uptake. CONCLUSION: FDG-PET can be
      used for evaluation of residual disease in patients treated for advanced
      seminoma. In cases of otherwise unexplained increased pulmonary FDG uptake in
      patients under treatment with bleomycin an evaluation for early BIP as a possible
      cause of this finding is warranted.

PMID- 17551257
TI  - Concomitant occurrence of facial cutaneous and parotid gland metastases from
      rectal cancer after preoperative chemoradiotherapy.
AB  - BACKGROUND: Unusual sites of metastasis to the parotid gland and face are
      reported in patients with colorectal cancer, but the localization to both sites
      at the same time has never been described so far. CASE REPORT: Here, we describe
      the case of a 76-year-old woman with a T3N1M0 G2 rectal adenocarcinoma, treated
      with preoperative chemoradiotherapy performed at suboptimal dosages due to
      unacceptable toxicity. At the end of the program, the re-staging demonstrated the
      presence of metastasis in both the left parotid gland and subcutaneously on the
      frontal region of her face while the primary locoregional tumour manifestation
      was radiologically down-staged (reduction in N staging from N1 to N0). The
      patient did not respond to any other treatment and died due to disease
      progression 15 months after the diagnosis. CONCLUSIONS: Metastatic tumours in the
      parotid gland are uncommon with a higher incidence of primary sites of the head
      and neck. Parotid involvement of rectal adenocarcinoma is also extremely rare,
      and concomitant involvement of both the parotid gland and the face was not
      previously described. In this case, we cannot rule out the hypothesis that the
      delay of surgical removal of the primary tumour and/or a specific action of
      concomitant chemoradiotherapy on the tumour cell phenotype could promote cancer
      cell spreading to unusual sites.

PMID- 17551258
TI  - Role of asymmetric dimethylarginine in inflammatory reactions by angiotensin II.
AB  - Previous investigations have demonstrated that angiotensin (Ang) II induces
      inflammatory reactions and asymmetric dimethylarginine (ADMA), an endogenous NOS
      inhibitor, might be a novel inflammatory factor. Endothelial cell activation was
      induced by incubation with Ang II or ADMA. Incubation with Ang II (10(-6) M) for
      24 h elevated the levels of ADMA and decreased the levels of nitrite/nitrate
      concomitantly with a significant increase in the expression of protein arginine
      methyltransferase and a decrease in the activity of dimethylarginine
      dimethylaminohydrolase (DDAH). Exposure to Ang II (10(-6) M for 24 h) also
      enhanced intracellular ROS elaboration and the levels of tumor necrosis factor
      (TNF)-alpha and interleukin (IL)-8, upregulated chemokine receptor CXCR2 mRNA
      expression, increased adhesion of endothelial cells to monocytes and induced a
      significant increase in the activity of nuclear factor (NF)-kappaB, which was
      attenuated by pretreatment with the Ang II receptor blocker losartan (1, 3 and 10
      muM). Exogenous ADMA (30 microM) also increased ROS generation and the levels of
      TNF-alpha and IL-8, decreased the levels of nitrite/nitrate, upregulated CXCR2
      gene expression, increased endothelial cell binding with monocytes and activated
      the NF-kappaB pathway, which was inhibited by pretreatment with losartan or L
      arginine. These data suggest that ADMA is a potential proinflammatory factor and
      may be involved in the inflammatory reaction induced by Ang II.

PMID- 17551259
TI  - Using intravascular autoradiography for an estimation of proliferative activity
      of rat mesenteric microvessel endothelial cells during the first month of
      postnatal development.
AB  - BACKGROUND/METHODS: We applied a novel method for studying endothelial cells (EC)
      by using autoradiography of cells labeled by 3H-thymidine: photo emulsion was
      administered into the vascular bed. In the flat transparent organ, this method
      allows to compare the mitotic activity of endothelium (MAE) depending on vessel
      diameter and animal age. RESULTS: The number of the labeled ECs in animals was
      found to be almost equal in all vessels at the same age. The amount of labeled
      vessels and the density of the labeled nuclei increase towards near-capillary
      vessels of a diameter < or =10 microm. With age, MAE decreases in all categories
      of vessels. However, in 12-day-old animals, MAE temporarily increases. It was
      noted that high MAE in the bed of these rats precedes or coincides with the
      period of accelerated weight gain of the digestive system supplied by an increase
      in organ blood flow. CONCLUSIONS: By using the endothelial autoradiography method
      that we developed, we obtained the following evidence: (1) the number of ECs in
      the synthetic phase of the mitotic cycle in mesenterial vessels is approximately
      identical in animals of the same age, and (2) this number decreases with age,
      except during the period of accelerated organ growth, when MAE increases.

PMID- 17551260
TI  - Waist circumference adds to the variance in plasma C-reactive protein levels in
      elderly patients with metabolic syndrome.
AB  - BACKGROUND: C-reactive protein (CRP), a nonspecific marker of the inflammatory
      status, is associated with cardiovascular disease risk factors and may be an
      important feature of the metabolic syndrome (MSX) in middle-aged subjects.
      OBJECTIVES: We assessed the relationship of CRP levels to specific components of
      MSX and other potential determinants in apparently healthy elderly subjects
      living in the South of France. METHODS: In the framework of the population-based
      POLA (Pathologies Oculaires Liees a l'Age) Study, performed in 2,404 subjects
      aged 60 years or more, we measured the plasma CRP levels. All subjects with known
      systemic inflammatory diseases, such as chronic bronchitis, cardiovascular
      disease, and diabetes, and those who were on systemic steroid therapy as well as
      subjects with CRP levels >10 mg/l were excluded from the study, leaving 1,709
      subjects for the statistical analyses. MSX was defined according to NCEP
      (National Cholesterol Education Program) criteria. Other potential determinants
      were assessed through interviewer-based questionnaire. RESULTS: We grouped the
      subjects into three categories based on the 75th and 25th percentiles,
      corresponding to 3.05 and 0.82, respectively. We compared subjects in the highest
      quartile, i.e., with CRP >/=3.05 mg/l, with those in the two intermediate
      quartiles, i.e., with 0.82 < CRP < 3.05, and those in the lowest quartile, i.e.,
      with CRP <0.82 mg/l according to gender. MSX, which had a prevalence of 31%, was
      significantly associated with elevated CRP levels. Among MSX components, the
      strongest positive association with the highest quartile of CRP was with waist
      circumference in males as well as in females (age-adjusted odds ratio OR 3.06 and
      95% confidence interval CI 1.82-5.14; OR 7.04 and 95% CI 4.79-10.34,
      respectively). Each component of the MSX, such as abnormal fasting plasma glucose
      (OR 2.90, 95% CI 1.69-4.99), triglycerides (OR 1.96, 95% CI 1.30-2.96), high
      density lipoprotein cholesterol (OR 2.31, 95% CI 1.61-3.30), and blood pressure
      (OR 1.66, 95% CI 1.12-2.45), was significantly associated with high CRP values in
      elderly women only. In men, only current smoking was significantly associated
      with high CRP levels (OR 1.52, 95% CI 1.04-2.2). In multivariate analysis, the
      waist circumference remained significantly associated with high CRP levels, with
      a graded effect of CRP quartile whatever the gender. In men, current and former
      smoking remained significantly associated with the CRP levels. In women, the
      association observed in univariate analysis with fasting glucose or hypertension
      did not reach statistical significance in the multivariate analysis, while only a
      weak association could be observed with lipid parameters such as triglycerides
      and high-density lipoprotein cholesterol. CONCLUSIONS: Abdominal adiposity adds
      to the variance in plasma CRP levels in elderly patients with MSX. This suggests
      that weight loss or other interventions targeted at adipocyte-related
      inflammation may represent an important means to prevent subclinical inflammation
      in the elderly, bearing a high risk of cardiovascular disease.

PMID- 17551261
TI  - Non-replication and inconsistency in the genome-wide association setting.
AB  - Non-replication and inconsistency had been common features in the search for
      common variants of candidate genes affecting the risk of complex diseases. They
      may continue to require attention in the current era, when massive hypothesis
      free testing of genetic variants is feasible. An empirical evaluation of the
      early experience with genome-wide association (GWA) studies suggests several
      examples where proposed associations have failed to be replicated by subsequent
      investigations. Non-replication and inconsistency is defined here in the
      framework of cumulative meta-analysis. Ideally, associations exist, GWA finds
      them, and subsequent investigations should replicate them. However, a number of
      other possibilities need to be considered. No common genetic variants may
      associate with the phenotype of interest and GWA may find nothing; or
      associations may exist, but GWA may miss them. Associations that do not exist may
      be falsely selected by the GWA and subsequent studies may appropriately refute
      them or falsely replicate them. Finally, GWA may find true associations that are
      nevertheless falsely non-replicated in the subsequent studies; or associations
      may be genuinely inconsistent across study populations. A list of options is
      presented for consideration in each of these scenarios.

PMID- 17551262
TI  - Central type 2 corticotropin-releasing hormone receptor mediates hypothalamic
      pituitary-adrenocortical axis activation in the rat.
AB  - In an attempt to clarify the role of the type 2 corticotropin-releasing hormone
      (CRH) receptor (CRHR-2) in the brain in activation of the hypothalamic-pituitary
      adrenocortical axis, we conducted experiments using male Wistar rats. First, an
      injection of urocortin-2 (7.5 microg) into the lateral ventricle resulted in
      transient increases in CRH heteronuclear RNA (hnRNA) in parvocellular
      paraventricular nucleus (PVN) and in plasma adrenocorticotropic hormone (ACTH),
      whereas sustained increases in arginine vasopressin (AVP) hnRNA and c-fos mRNA in
      the parvocellular PVN were observed as compared with vehicle treatment.
      Pretreatment with the selective CRHR-2 antagonist antisauvagine-30 (20 microg)
      into the lateral ventricle 15 min prior to agonist injection attenuated the
      stimulatory effects of urocortin-2 on the above-mentioned hypothalamic-pituitary
      adrenal axis variables. These effects were similar or rather more potent than
      those induced by pretreatment with 50 microg of alpha-helical CRH. Second, we
      found longer-lasting increases in CRH and AVP hnRNA and c-fos mRNA in
      parvocellular PVN and in plasma ACTH following central administration of
      urocortin-3 (7.5 microg) than following urocortin-2. Pretreatment with
      antisauvagine-30 antagonized the effects of urocortin-3 on the above-mentioned
      variables. Finally, central administration of antisauvagine-30 as well as alpha
      helical CRH profoundly attenuated restraint-stress-induced increases in AVP
      hnRNA. However, alpha-helical CRH, but not antisauvagine-30, attenuated restraint
      stress-induced increases in CRH hnRNA in the PVN. Both antagonists transiently
      attenuated stress responses of c-fos mRNA in PVN and plasma ACTH. These results
      indicate that there is a CRHR-2-mediated mechanism in the brain that stimulates
      CRH- and AVP-producing neurons in the PVN which results in the promotion of
      plasma ACTH secretion.

PMID- 17551263
TI  - GABA inhibition of cyclic AMP production in immortalized GnRH neurons is mediated
      by calcineurin-dependent dephosphorylation of adenylyl cyclase 9.
AB  - The neurotransmitter gamma-aminobutyric acid (GABA) is an important modulator of
      gonadotropin-releasing hormone (GnRH), and consequently of reproduction. GABA,
      acting via ionotropic GABAA receptors, exerts a biphasic effect on GnRH secretion
      in immortalized GnRH cells. The initial increase in GnRH secretion is triggered
      by a sharp rise in [Ca2+]i, while the progressive decline of GnRH levels that
      follows is paralleled by reduced levels of intracellular cAMP. The experiments
      described here were designed to explore the potential signaling pathways involved
      in this novel GABAA ionotropic inhibition of cAMP synthesis in GT1-7 cells. Using
      RT-PCR and real-time PCR, we found that GT1-7 cells express 8 of 9 known membrane
      adenylyl cyclase (AC) isoforms, including a large proportion of AC3 and AC9, as
      well as AC5 and AC6, all of which are negatively regulated by increases in
      [Ca2+]i. In contrast, isoforms of AC that are positively regulated by [Ca2+]i
      were barely detectable (AC1) or undetectable (AC8). Pharmacological activation of
      L-type voltage-operated calcium channels with BayK 8644 produced a decrease in
      [cAMP]i similar to that induced by GABA, while blocking these calcium channels
      with verapamil reversed the effect of GABA on cAMP synthesis. Furthermore,
      blocking calcineurin with deltamethrin, FK-506 or cyclosporin A blocked the
      inhibitory effect of GABA on [cAMP]i, supporting the involvement of AC9 in this
      effect. In addition, blocking Ca2+/calmodulin-dependent protein kinase II
      (CamKII) with KN-62 partially reversed the action of GABA, suggesting that AC3
      may also be involved in this effect. Finally, GABA increased phosphatase activity
      in a calcium-dependent manner, an effect blocked by calcineurin inhibitors.
      Collectively, our results show that the ionotropic action of GABA via the
      activation of GABAA receptors can decrease AC activity in immortalized GnRH
      neurons, and that the effect of GABA appears to be mediated by a transient
      increase in [Ca2+]i followed by activation of calcineurin and CamKII, leading to
      dephosphorylation of AC9 and phosphorylation of AC3, respectively, and
      subsequently reducing the synthesis of cAMP.

PMID- 17551264
TI  - Dynamic visualization of lung sounds with a vibration response device: a case
      series.
AB  - BACKGROUND: The field of computer-assisted mapping of lung sounds is constantly
      evolving and several devices have been developed in this field. OBJECTIVES: Our
      objective was to evaluate a new computer-assisted lung sound imaging system,
      'vibration response imaging' (VRI), that records and creates a dynamic image of
      breath sounds. We postulated that the VRI display format would qualitatively and
      quantitatively reveal breath sound distribution throughout the breathing cycle.
      METHODS: Lung sounds were recorded from 5 healthy adults and 14 patients with
      various respiratory illnesses using VRI. The lung sounds were processed by the
      VRI software, which incorporates an algorithm to convert breath sounds in the
      frequency range of 150-250 Hz to a dynamic image and quantitative assessment of
      breath sound distribution. RESULTS: Images and quantifications from recordings of
      the healthy adults showed distinct patterns for inspiration and expiration.
      Images and quantifications from the subjects with respiratory illness differed
      substantially from the images of the healthy subjects. Both healthy and
      pathological subjects presented some expected characteristics of breath sound
      distribution. CONCLUSIONS: The VRI device may provide a new perspective in
      acoustic imaging and quantification of breath sounds by adding aspects of time
      analysis and quantification of distribution to existing methods. Further studies
      will be required in order to establish reliability of repeated recordings and to
      validate the sensitivity of the system in detecting various lung pathologies.

PMID- 17551265
TI  - Characteristics of neural stem cells expanded in lowered oxygen and the potential
      role of hypoxia-inducible factor-1Alpha.
AB  - It has recently been reported that hypoxia promotes the survival and
      proliferation of neural stem cells (NSCs). In the present study, we examine the
      differentiation ability of neural precursors expanded under lowered oxygen
      conditions, and the potential role of hypoxia-inducible factor (HIF)-1alphain
      vitro, which is the key molecule in response to lowered oxygen. The NSCs were
      cultured in a 3% O(2) environment for 3 days, and differentiated with 1% fetal
      bovine serum (FBS) for another 5-7 days, and the cell lineage was evaluated by
      immunohistochemistry, flow cytometry and HPLC. Compared with the normal
      condition, the NSCs cultured in hypoxia (3% O(2)) displayed an increase in the
      percentage of neurons. Especially the percentage of TH-positive neurons
      differentiated from NSCs in lowered oxygen increased significantly; the dopamine
      (DA) content in the medium was higher than under normal conditions. These data
      indicate that lowered oxygen favors dopaminergic differentiation. We then
      examined the expression of HIF-1alpha during differentiation of NSCs. The levels
      of HIF-1alpha mRNA expression under 3% oxygen did not change as compared with
      those under normal conditions. However, HIF-1alpha protein expression was higher
      from 3 to 72 h during hypoxia than under normal conditions. Overexpression of HIF
      1alpha significantly increased the number of TH-positive cells and the DA content
      in culture medium under normal conditions. These results suggest that HIF-1alpha
      is involved in the regulation of dopaminergic differentiation of NSCs in lowered
      oxygen. This study may also offer a new approach to yield DA neurons using a
      physical factor.

PMID- 17551266
TI  - Carvedilol prevents and reverses hypertrophy-induced cardiac dysfunction.
AB  - BACKGROUND/AIMS: Histological studies have provided evidence that carvedilol can
      prevent cardiac hypertrophy in spontaneously hypertensive-stroke prone rats (SP)
      fed a high-fat and -salt diet. However, the effects of carvedilol on cardiac
      function have not been studied in these animals. In addition, the ability of
      carvedilol to reverse established cardiac hypertrophy and dysfunction under these
      conditions remains to be determined. Here we have evaluated the ability of
      carvedilol to prevent and reverse cardiac hypertrophy and progressive dysfunction
      using echocardiography. METHODS: Two echocardiology studies were conducted to
      determine the effects of carvedilol treatment on cardiac hypertrophy and
      dysfunction. In the first prevention study, four groups of rats were evaluated.
      SP were fed a high-fat (24.5% in food) and high-salt (1% in water) diet (SFD)
      without (SP-SFD control group) or with carvedilol (SP-SFD carvedilol group;
      carvedilol concentration 2,400 parts per million) for 18 weeks. Carvedilol was
      administered in the food at an optimum concentration (i.e. known to provide
      clinically relevant blood concentrations and reduce cardiac hypertrophy
      determined from previous studies). In addition, SP and WKY rats were fed a normal
      diet (SP normal diet group and WKY normal diet group). These groups are known to
      not develop the same significant cardiac hypertrophy and dysfunction within this
      limited time of study, and provided two more normal control groups for
      comparison. In the second reversal study, one group of SP was fed SFD for 12
      weeks (SP-SFD pretreatment period) to induce cardiac hypertrophy. Carvedilol
      (2,400 parts per million) was then added to the diet for an additional 6 weeks
      (SP-SFD carvedilol treatment period). RESULTS: In the first prevention study,
      carvedilol prolonged longevity (p < 0.05) and prevented left-ventricular
      hypertrophy and dysfunction (p < 0.05; SP-SFD control vs. SP-SFD carvedilol
      group). M-mode-measured and -calculated parameters demonstrated that carvedilol
      treatment in the SP-SFD carvedilol group prevented increases in left-ventricular
      wall thickness (p < 0.05) and decreases in diastolic chamber diameter and volume,
      stroke volume, ejection fraction and cardiac output (all p < 0.05) that occurred
      in the SP-SFD control group. Further, cardiac measurements in the SP-SFD
      carvedilol group were normalized to levels similar to those in the SP and WKY
      normal diet groups. All SFD-fed groups exhibited similar, significantly elevated
      blood pressure during the study. In the second reversal study, carvedilol
      treatment for 6 weeks reversed the cardiac hypertrophy and dysfunction that
      developed in SP-fed SFD for 12 weeks prior to carvedilol intervention. Under
      these conditions, carvedilol improved/normalized left-ventricular wall thickness,
      diastolic ventricular-chamber diameter and volume, stroke volume, ejection
      fraction and cardiac output (all p < 0.05). CONCLUSIONS: These data indicate that
      carvedilol provides protection from and facilitates reversal of progressive
      cardiac remodeling and dysfunction in this SP-SFD model of cardiac
      hypertrophy/heart failure. Since these effects occurred in the absence of effects
      on blood pressure, other known actions of carvedilol, especially its antioxidant
      activity, for example, may explain this significant cardiac protection. In
      addition, research using this SP-SFD model of cardiac hypertrophy/end-organ
      injury appears to translate well to human cardiovascular disease.

PMID- 17551267
TI  - Modulation of corticotropin-releasing hormone type 2 receptor and urocortin 1 and
      urocortin 2 mRNA expression in the cardiovascular system of prairie voles
      following acute or chronic stress.
AB  - The purpose of this study was to compare the effects of an acute stressor
      (restraint) versus a chronic stressor (social isolation) on the expression of
      mRNAs for corticotropin-releasing hormone receptor type 2 (CRH-R2) and urocortin
      1 (Ucn 1) and urocortin 2 (Ucn 2) in the cardiovascular system of socially
      monogamous prairie voles of both sexes. Acute restraint for 1 h was followed by a
      marked increase in plasma corticosterone, and when the animals were re-paired for
      1 day, the increment of corticosterone was normalized. However, following chronic
      social isolation for 4 weeks, plasma corticosterone did not differ significantly
      from the levels measured in animals living in pairs. Restraint or isolation
      significantly decreased CRH-R2 mRNA in ventricle, atria, and aorta; however, when
      these animals were re-paired for 1 day, the modulation of CRH-R2 mRNA was
      normalized in restraint but not in isolated animals. Restraint stress increased
      the Ucn 1 mRNA expression in the heart of female and male prairie voles, and when
      the animals were re-paired, the modulation of Ucn 1 mRNA expression was
      normalized. However, chronic isolation showed no effect on cardiac Ucn 1 mRNA
      expression. Although acute restraint stress produced no effect on the cardiac Ucn
      2 mRNA expression, chronic isolation was followed by an increased heart Ucn 2
      mRNA expression in both sexes. When the isolated animals were re-paired for 1
      day, the cardiac Ucn 2 mRNA expression remained upregulated. The results of the
      present study reveal that acute restraint as well as social isolation can have
      significant consequences for the modulation of gene expression for the CRH-R2 and
      the urocortin peptides in cardiovascular tissue in female and male prairie voles.

PMID- 17551268
TI  - [Administration and dosing of gentamicin (data from Kaunas University of Medicine
      Hospital)].
AB  - The aim of the study was to analyze the treatment with gentamicin and possible
      nephrotoxicity of this antibiotic in patients treated in surgical and internal
      medicine departments of Kaunas University of Medicine Hospital. MATERIALS AND
      METHODS: A total of 105 case histories obtained from archive of our hospital were
      analyzed: 59 case records from surgical and 46 from internal medicine
      departments. Data were collected regarding indications for the administration of
      gentamicin, its dosage, duration of treatment, and patients' renal function at
      the beginning and during the treatment. RESULTS: There were more than 30% of
      patients older than 65 years. Gentamicin was administered in 14 (23.73%) surgical
      inpatients to prevent postoperative infection; 45 (76.27%) surgical and 46 (100%)
      internal medicine inpatients received gentamicin because of symptoms of
      infection. Half of the patients were treated empirically. In 87.62% of cases,
      gentamicin was administered at a dose of 240 mg; all 105 patients received it
      once per day. Before treatment, renal function was not evaluated in 11.86% of
      surgical and in 19.56% of internal medicine inpatients, and during treatment, it
      was examined only in one-third of patients. The duration of the treatment was
      5.932+/-2.392 days (range 2-13 days) in surgical and 8.283+/-3.344 days (range 3
      19 days) in internal medicine inpatients. CONCLUSIONS: More than half of patients
      received empirical treatment with gentamicin. Not enough attention has been paid
      to the evaluation of renal function before and during treatment. The duration of
      treatment was too long.

PMID- 17551269
TI  - [Primary glomerulopathies in Lithuania: a retrospective analysis of renal biopsy
      cases (2000-2006)].
AB  - A retrospective study of 1363 native kidney biopsies, performed at Lithuanian
      nephrology units and investigated at the National Center of Pathology during the
      period of 2000-2006, was carried out. Inflammatory glomerulopathies constituted
      63.6% of all primary glomerulopathies (834 cases); IgA nephropathy was the most
      frequent disease (35.0%). The incidence of membranoproliferative
      glomerulonephritis decreased from 22.6% reported in Lithuania previously (1995
      1999) to 16.7% in this study; however, it was still higher compared to most
      European countries. Extracapillary proliferative glomerulonephritis and diffuse
      endocapillary proliferative glomerulonephritis accounted for 9.1% and 4.4%,
      respectively. Noninflammatory glomerulopathies were relatively rare: focal and
      segmental glomerulosclerosis made up 14.8%; minimal change disease, 9.7%;
      membranous nephropathy, 7.4%. However, their incidence increased compared to the
      previously reported in 1995-1999 (9.5%, 5.8%, and 4.3%, respectively). It can be
      concluded that inflammatory glomerulopathies were predominant in Lithuania in
      2000-2006; however, these glomerulopathies were less prominent as compared to the
      previously reported data in 1995-1999.

PMID- 17551270
TI  - [Etiology, prevalence of chronic renal failure and growth retardation in
      Lithuanian children].
AB  - The aim of the study was to evaluate the causes, prevalence, and grades of
      chronic renal failure in Lithuanian children and to assess its influence on
      children's growth. The study was performed in Vilnius University Children's
      Hospital and Clinic of Children's Diseases, Kaunas University of Medicine. By
      March 31, 2006, 65 children with chronic renal failure had been registered. The
      prevalence was 88.3 cases per million children. The mean age was 10.8+/-4.9
      years. The leading causes of chronic renal failure were congenital diseases (37%)
      and obstruction with interstitial nephritis (33.8%). At presentation, 23 (35.40%)
      children had mild, 17 (26.15%) had moderate, 9 (23.85%) had severe renal failure,
      and 16 (24.6%) had end-stage renal disease. Fourteen (21.54%) children were below
      the third percentile in height for their age. Growth failure was observed in one
      (4.35%) child with Grade 1 renal failure. The deterioration of renal function had
      a significant influence on growth impairment, and 13 (30.95%) children with
      glomerular filtration rate of less than 60 mL/min/1.73 m2 and 7 (43.75%) with end
      stage renal disease had a height below the third percentile. Growth retardation
      as one of the symptoms of impairment of children's physical development depends
      on the severity of renal function.

PMID- 17551271
TI  - [Postinfectious glomerulonephritis in children in Lithuania during 1995-2004:
      prevalence and clinical features].
AB  - During the period of 1995-2004, acute postinfectious glomerulonephritis was
      diagnosed in 322 children aged 1-16 years. An outbreak of acute postinfectious
      glomerulonephritis was registered in 1995, with a prevalence of 8.3 cases per
      100,000 children; during 2003-2004 prevalence decreased and it was 2.2-2.4 cases
      per 100,000 children. Acute postinfectious glomerulonephritis was most frequently
      caused by upper respiratory tract infection (28.3%), following by tonsillitis
      (24%) and skin infection (24%). The mean interval between diagnosis of primary
      infection and onset of acute postinfectious glomerulonephritis was 14 days and
      did not differ by infection. The disease was more common in autumn (96 of the 322
      cases, P<0.05). There were 4.3% of familial cases; no relapses occurred. Edema
      was observed in 70.3% of patients; 55.5% had elevated blood pressure according to
      their age. There were no proteinuria and hematuria in 17.6% and 1.7% of patients,
      respectively. Short-term renal failure was diagnosed in 32.9% of patients; in two
      cases, acute renal failure was severe and hemodialysis was started. No patient
      died.

PMID- 17551272
TI  - [The clinical course and long-term outcome of hemolytic-uremic syndrome in
      children].
AB  - The aim of this study was to evaluate the long-term outcome of hemolytic-uremic
      syndrome in children and the dependence of outcome on severity of the acute phase
      of the illness. We analyzed data of 20 children who were hospitalized and treated
      at the Clinic of Children's Diseases, Kaunas University of Medicine Hospital,
      during 1995-2006. Data were obtained from case histories and outpatient case
      records with the help of prepared questionnaire. The course of acute disease and
      health status were evaluated at discharge from hospital and at 6-month, 1-year,
      and 3-year follow-ups. There were 8 boys and 12 girls in the study group; their
      age ranged from 3 months to 12 years. According to the clinical course of the
      acute phase of the illness, children were divided into two groups. Group A
      (severe course) consisted of 15 patients with blood leucocytosis (more than
      20x10(9)/L) and signs of CNS involvement, who required renal replacement therapy.
      Group B (mild course) consisted of five children who did not have such symptoms.
      Twelve (60%) children underwent dialysis during acute illness; two patients died
      (10%). One (20%) patient in Group B had proteinuria, four (80%) had renal
      insufficiency, and three (60%) had arterial hypertension at discharge from
      hospital. Subsequently these changes disappeared, and 3 years later arterial
      hypertension was detected in 1 (25%) patient in Group B. Eight (61.5%) patients
      from Group A had renal insufficiency, nine (69.2%) had proteinuria, and two (15.4
      %) had arterial hypertension at discharge from hospital. Three years later from
      the onset of the disease, two (20%) patients had arterial hypertension,
      proteinuria was detected in two (20%) patients, and renal insufficiency remained
      in six (60%) children. Our data revealed that the outcomes of the disease are
      strongly influenced by the severity of the acute phase of the illness.

PMID- 17551273
TI  - [Frequency, etiology, and outcomes of acute renal failure (data of Kaunas
      University of Medicine Hospital in 1995-2006)].
AB  - The aim of this study was to determine the frequency, etiology, and outcomes of
      acute renal failure. We retrospectively collected data on all patients (n=1653)
      who received renal replacement therapy for acute renal failure at the Kaunas
      University of Medicine Hospital during 1995-2006. The number of patients with
      acute renal failure increased nine times during the 11-year period. The mean age
      of patients was 59.76+/-17.52 years and increased from 44.97+/-17.1 years in 1995
      to 62.84+/-16.49 years in 2006. The most common causes of acute renal failure
      were renal (n=646, 39%), prerenal (n=380, 23%), and obstructive (n=145, 9%). The
      renal replacement therapy was discontinued because of recovery of renal function
      in 49.9% of cases. The overall hospital mortality rate was 45.1%. Renal function
      did not recover in 6.7% of patients. The mortality rate over the 11-year period
      varied from 37.8 to 57.5%. The highest mortality rate was in the neurosurgical
      (62.3%) and cardiac surgical (61.8%) intensive care units. High mortality rate
      (more than 50%) was in the groups of patients with acute renal failure that was
      caused by hepatorenal syndrome, shock, sepsis, and reduced cardiac output.

PMID- 17551274
TI  - [Acute renal failure in patients with alcoholic surrogate intoxication].
AB  - Intoxications with alcoholic surrogates are still frequent in Lithuania. The aim
      of this study was to evaluate the frequency, course, and effectiveness of
      treatment and outcomes of acute renal failure in patients with alcoholic
      surrogate intoxication. We have analyzed the case histories of 94 patients with
      alcoholic surrogate poisoning. Patients were treated in the Clinic of Nephrology,
      Kaunas University of Medicine Hospital, during 1997-2006. Fifty-three cases of
      poisoning with unspecified ethanolic surrogates, which did not provoke acute
      renal failure, were identified, and we did not analyze them in detail. Forty-one
      cases of intoxication with nonethanolic surrogates were identified, and acute
      renal failure developed in 34 patients. In 31 of the 41 patients, hemodialysis
      was started for toxin removal. Among eight patients in whom treatment was started
      within 12 hours of intoxication, seven (87.5%) patients had no acute renal
      failure. In the 23 remaining patients, treatment was started later than 12 hours
      after intoxication, and acute renal failure was diagnosed in all of them. Three
      patients died within 48 hours after hospitalization because of severe
      intoxication. CONCLUSION. Acute renal failure developed in 82.9% of patients
      poisoned with nonethanolic surrogates. In such cases, when hemodialysis for toxin
      removal was started up to 12 h after poisoning, acute renal failure developed
      significantly rarely.

PMID- 17551275
TI  - [The prevalence of major risk factors for chronic kidney disease among patients
      in primary health care centers].
AB  - The aim of the study was to investigate the prevalence for high-risk factors for
      chronic kidney disease among patients in primary health care centers and to
      assess diagnostic strategy carried out by family doctors. RESULTS: We analyzed
      case records (n=4082) of patients aged more than 18 years in four family doctor's
      practices of Kaunas city. The ratio of female to male was 1.4:1. The major risk
      factors for chronic kidney disease (severe hypertension, diabetes, kidney
      diseases, and severe ischemic diseases) were identified in 458 patients: 287
      (62.66%) women and 171 (37.34%) men. It accounted for 11.2% of all patients. They
      were significantly older as compared to all patients (66.96+/-14.34 vs. 49.86+/
      18.54 years, P<0.0001). The most common risk factors were as follows:
      hypertension (62.66%), primary kidney diseases (33.84%), diabetes (20.96%), and
      complicated ischemic disease (6.11%). Of the 458 patients, 366 (79.9%) had one
      and the remaining patients had several risk factors. During the last 24 months,
      family doctor evaluated kidney function and urinanalysis in 24.4% and 53.6% of
      patients with high-risk factors, respectively. While examining these patients
      (n=91), it was determined that even in 54.95% of them, glomerular filtration rate
      was lower than 60 mL/min/1.73 m2. CONCLUSIONS: The major risk factors for chronic
      kidney disease were identified in 11.2% of patients from primary health care
      centers. Most of them were older than 75 years. The most common risk factor was
      arterial hypertension. The assessment of kidney function in these patients by
      family doctor was insufficient. A thorough examination of the patients with major
      risk factors revealed chronic kidney insufficiency in half of them.

PMID- 17551276
TI  - [Comparison of methods for evaluating renal function (Data of Kaunas University
      of Medicine Hospital in 2006)].
AB  - Cockcroft-Gault formula and Modification of Diet in Renal Disease (MDRD) equation
      are widely used as indirect estimates of renal function. The precision and
      reliability of these formulas regarding kidney function are still discussed. The
      aim of our study was to evaluate glomerular filtration rate by different methods
      and compare the results. Data on patients in whom renal function was evaluated at
      the Clinic of Nephrology of Kaunas University of Medicine Hospital in 2006 are
      presented in this article. Glomerular filtration rate was assessed based on 24
      hour endogenous creatinine clearance and calculated using three formulas:
      Cockcroft-Gault, abbreviated MDRD, and complete MDRD. Blood serum creatinine
      level was measured by the standardized Jaffe assay. Glomerular filtration rate
      was examined in 125 patients. Their mean age was 58.07+/-18.962 years. The mean
      endogenous creatinine clearance was 31.1287+/-31.14 783 mL/min. The mean
      glomerular filtration rate calculated by Cockcroft-Gault formula was 34.1220+/
      29.02 967 mL/min, by abbreviated MDRD formula was 29.8212+/-25.83 866 mL/min/1.73
      m2, and by complete MDRD formula was 28.6884+/-24.99 353 mL/min/1.73 m2. There
      was no statistically significant difference in mean glomerular filtration rates
      estimated using all methods in the evaluation of kidney function. When the
      reliability of formulas was analyzed depending on each stage of chronic kidney
      disease, it was found that Cockcroft-Gault and MDRD formulas, in contrast to
      endogenous creatinine clearance, did not precisely reflect kidney function in
      stages 1 and 2 of chronic kidney disease. Estimates by Cockcroft-Gault and MDRD
      formulas correctly showed decreased kidney function in stages 3 and 4 of chronic
      kidney disease. Formulas were not reliable, in contrast to endogenous creatinine
      clearance, when patients were in end-stage chronic kidney disease. CONCLUSIONS.
      Cockcroft-Gault and MDRD formulas are best for the evaluation of moderate degree
      of renal insufficiency, and in early stage of chronic kidney disease,
      underestimation of glomerular filtration rate is possible by using formulas.
      Estimates of glomerular filtration rate based on formulas are higher as compared
      to endogenous creatinine clearance measurements in end-stage chronic kidney
      disease.

PMID- 17551277
TI  - [Changes in hemodialysis adequacy in Lithuania during 1999-2005].
AB  - Despite the improvement of hemodialysis technique, mortality of chronic
      hemodialysis patients remains quite high. It considerably depends on dialysis
      adequacy. The aim of the study was to evaluate the adequacy of hemodialysis
      procedure and its changes in Lithuania during 1999-2005. Between 1999 and 2005 in
      December, all hemodialysis centers in Lithuania were annually visited, and data
      on the type of hemodialysis, duration of hemodialysis (hours per week), single
      pool Kt/V were collected from all hemodialysis patients. The percentage of
      patients on bicarbonate hemodialysis sharply increased from 57.9% in 1999 to 100%
      in 2001 (P<0.001), and the duration of hemodialysis procedure increased (67.3% of
      hemodialysis patients were dialyzed 12 and more hours per week in 2005 vs. 41.3%
      in 1999, P<0.001). The percentage of patients who were dialyzed three times per
      week increased from 51% in 1999 to 77% in 2005 (P<0.001). The mean Kt/V was
      0.81+/-0.53 in 1999, but it increased to 1.21+/-0.27 in 2005 (P<0.001). More than
      half (54%) of all hemodialysis patients in 2005 had Kt/V > or =1.2 vs. more than
      one-third (36%) in 1999 (P<0.001). The mean Kt/V of patients who were on dialysis
      three times per week was 1.25+/-0.6; two times per week, 1.30+/-0.8; and one time
      per week, 1.27+/-0.26 in 2003. In 2005, the results were 1.21+/-0.27, 1.22+/
      0.26, and 1.16+/-0.29, respectively (P>0.05). CONCLUSIONS. 1. The improvement of
      the quality of hemodialysis was observed in Lithuania during 1999-2005: a) from
      2001, patients received only bicarbonate hemodialysis; b) weekly duration of
      hemodialysis increased; c) Kt/V improved. 2. Despite the improvement of
      hemodialysis quality, it is not optimal yet and is associated with insufficient
      duration of hemodialysis.

PMID- 17551278
TI  - [Prevalence and quality of control of calcium and phosphorus metabolism disorders
      among Lithuanian hemodialysis patients in 2004 and 2005].
AB  - The aim of the study was to determine the prevalence and quality of control of
      disorders of calcium and phosphorus metabolism among patients on hemodialysis in
      Lithuania during the period of 2004-2005 and to assess rarely used methods of
      treatment such as parathyroidectomy and administration of calcimimetics. MATERIAL
      AND METHODS: All Lithuanian hemodialysis centers were visited, and data on
      disorders of calcium-phosphorus metabolism were collected in December 2004 and
      2005. The quality of control was evaluated according to Kidney Disease Outcome
      Quality Initiative recommendations. RESULTS: According to Kidney Disease Outcome
      Quality Initiative guidelines, normal parathyroid hormone levels were found in
      20.4% of hemodialysis patients in 2004 and 18.8% of hemodialysis patients in
      2005; normal levels of phosphate were in 41.9% and 39.4%, respectively; normal
      levels of calcium were observed in 44.7% of patients in 2004 and in 42.3% of
      patients in 2005. In 2005 as compared to 2004, there were statistically
      significantly more patients with low parathyroid hormone level (39.9% and 45.8%,
      respectively, P<0.05). Only in 5.6% of patients in 2004 and 3.9% of patients in
      2005, all four parameters of calcium-phosphate metabolism (calcium, phosphate,
      and of parathyroid hormone levels and calcium-phosphate product) were within the
      normal range. No parameters in the normal range were found in 17-20% of patients.
      The use of alfacalcidol significantly increased: 316 (30.8%) patients in 2004 and
      388 (35.7%) patients in 2005 were treated with alfacalcidol (P<0.05).
      Alfacalcidol was prescribed for 16.5% of patients in 2004 and for 17% of patients
      in 2005, in whom parathyroid hormone level was below the normal range in the
      presence of hypercalcemia and hyperphosphatemia. The use of calcimimetics was
      considered rational in 142 (13.8%) patients in 2004 and 119 (10.9%) patients in
      2005. According to the data of our study, parathyroidectomy was indicated in 19
      (1.85%) patients in 2004 and 17 (1.56%) patients in 2005. CONCLUSIONS: According
      to Kidney Disease Outcome Quality Initiative recommendations, the control of
      disorders of calcium-phosphate metabolism in Lithuanian hemodialysis patients was
      insufficient in 2004 and 2005. One-third of the patients were treated with
      alfacalcidol when parathyroid hormone level was low and hypercalcemia and
      hyperphosphatemia persisted. Calcimimetics for the treatment of secondary
      hyperparathyroidism were administered in about 10% of patients.

PMID- 17551279
TI  - [Infection-related hospitalization of hemodialysis patients].
AB  - Infection is an important cause of morbidity and mortality in hemodialysis
      patients. These patients are frequently hospitalized for infections. The
      objective of our study was to evaluate hospitalization rate for infections and to
      determine risk factors for infection-related hospitalizations of hemodialysis
      patients in Kaunas region, Lithuania. Ambulatory case records of 533 patients
      with end-stage renal disease, dialyzed in all hemodialysis centers in Kaunas
      region during the period of 2001-2004, were analyzed. Data on patient's condition
      and routine laboratory tests were collected in November of 2001, 2002, and 2003.
      These patients then were followed up for the next 12 months in order to evaluate
      infection-related hospitalization rate. All patients were considered new patients
      every year, and general analysis of three-year data was performed. Statistical
      analyses were carried out using SPSS (Statistical Package for Social Sciences)
      and STATISTICA. Univariate statistical analysis was performed comparing the
      groups of patients that were hospitalized because of infections and were not
      hospitalized. Relative risk of infection-related hospitalization was estimated
      using Cox regression evaluating the time to first infection-related
      hospitalization. The unadjusted infection-related hospitalization rate was 0.2
      per patient a year (18% of all hospitalizations). The median length of hospital
      stay for infections was 11 days. Univariate statistical analysis showed a
      statistically significant association between infection-related hospitalizations
      and diabetes (P=0.02); lower hemoglobin (P<0.0001), creatinine (P=0.045), and
      albumin (P=0.01) concentrations; higher interdialytic weight gain (P=0.01).
      Multivariate Cox regression analysis revealed that only hemoglobin concentration
      (P<0.001, RR=0.96), interdialytic weight gain (P=0.002, RR=1.38), and creatinine
      level (P=0.02, RR=0.99) were important risk factors for infection-related
      hospitalization. Relative risk of infection-related hospitalization was 4.4 times
      greater when hemoglobin concentration was less than 100 g/L (P<0.001) and 1.9
      times greater when interdialytic weight gain was more than 4% of body weight
      (P=0.008). CONCLUSION. In Kaunas region, infection-related hospitalizations
      accounted for 18% of all hospitalizations. Anemia, creatinine level, and
      interdialytic weight gain were important risk factors for infection-related
      hospitalization of hemodialysis patients.

PMID- 17551280
TI  - [Prevalence of antibodies to hantavirus among hemodialysis patients with end
      stage renal failure in Kaunas and its district].
AB  - The objective of this study was to investigate the prevalence of antibodies to
      hantaviruses among hemodialysis patients with end-stage renal failure in Kaunas
      and its district. MATERIAL AND METHODS: Serums of 218 patients from four dialysis
      centers of Kaunas district were tested by using the immunoglobulin G antibody
      capture enzyme-linked immunosorbent assay (ELISA). The reactivity of ELISA
      positive sera was proven in Western blot tests using various hantavirus
      recombinant nucleocapsid proteins. The yeast-expressed nucleocapsid proteins were
      used for testing. RESULTS: Antibodies against Dobrava/Hantaan and Puumala
      hantaviruses were found in 16 patients (seroprevalence 7.4%). Most of the sera
      were positive for Dobrava hantavirus (81%). The ratio of males to females was
      1.2:1. Seroprevalence was significantly higher in older patients. CONCLUSIONS:
      Results indicate that antibodies to two hantaviruses (Dobrava/Hantaan virus and
      Puumala virus) are prevalent among hemodialysis patients in Kaunas district with
      approximately the same seroprevalence as in neighboring countries.

PMID- 17551281
TI  - [The prevalence of Fabry's disease among male patients on hemodialysis in
      Lithuania (a screening study)].
AB  - Fabry's disease is an X-linked inborn error of glycosphingolipid metabolism
      caused by a deficiency of the lysosomal hydrolase alpha-galactosidase A. Due to
      deficiency of this enzyme activity, a progressive lysosomal accumulation of
      glycosphingolipids, in particular globotriaosylceramide, takes place within
      endothelial cells and cells of the vascular and nervous systems, myocardial
      cells, endothelial, and mesangial and epithelial cells of the kidney, eventually
      leading to organ dysfunction. The degree of renal involvement generally
      correlates with the progression of glycosphingolipid accumulation and may lead to
      renal insufficiency and failure. Renal dysfunction can progress to end-stage
      renal failure, which usually occurs in the third to fifth decade of life. The
      prevalence of this disease among males on chronic hemodialysis is different in
      various countries. Screening for alpha-galactosidase A deficiency by blood spot
      tests was performed among 536 male dialysis patients in all 42 hemodialysis
      centers in Lithuania in the period of April-June, 2005. All tests, showed normal
      galactosidase A enzymatic activity. CONCLUSION: No patient with suspicion of
      Fabry's disease was found by this screening method.

PMID- 17551282
TI  - [The level of endotoxins in hemodialysis water and dialysate].
AB  - Hemodialysis is a process when the blood of patients contacts with dialysate
      through a semipermeable membrane. Water used for dialysis is not sterile.
      Microorganisms cannot pass through the membrane pores, but bacterial endotoxins
      can diffuse to the blood of patients. Several acute and long-term complications
      (pyrogenic reactions, silent chronic inflammation, malnutrition) in dialysis
      patients might be associated with dialysate contamination. The aim of this study
      was to determine the level of endotoxins in hemodialysis water and dialysate in
      several hemodialysis centers of different Lithuanian cities. MATERIAL AND
      METHODS: Material was dialysis water (n=6) and dialysate (n=14) from six
      hemodialysis centers in three different cities of Lithuania. Bacterial endotoxin
      levels were measured using a sensitive Limulus Amebocyte Lysate (LAL) assay.
      RESULTS AND CONCLUSIONS: The level of endotoxins was less than 0.25 endotoxin
      unit (EU)/mL in all hemodialysis water (n=6) and dialysate (n=14) samples. One
      sample of water (16.7%) and two of dialysate (14.3%) had the level of endotoxins
      above 0.03 EU/mL. Therefore, the level of endotoxins in hemodialysis water and
      dialysate in studied Lithuanian hemodialysis centers (n=6) complied with the
      recommendations of the European Pharmacopoeia and the ERA-EDTA best practice
      guidelines for conventional dialysis modalities. The level of endotoxins in
      dialysate of five Lithuanian hemodialysis centers complied with the
      recommendations of the ERA-EDTA best practice guidelines for ultrapure dialysate.

PMID- 17551283
TI  - [Estimated average yearly treatment expenditures for hemodialysis patients (data
      of Kaunas University of Medicine Hospital in the year 2005)].
AB  - With increasing number of hemodialysis patients, expenditures for the treatment
      of hemodialysis patients are rising every year. The objective of our study was to
      collect and analyze the data on estimated average treatment expenditures, which
      were covered by State Patients' Fund, for patients undergoing hemodialysis in
      Kaunas University of Medicine Hospital in 2005 and the costs of medications paid
      by patient and to compare with the analogical data of the year 2001. We analyzed
      ambulatory case records of all 106 patients with end-stage renal disease who were
      hemodialyzed in Kaunas University of Medicine Hospital from November 1, 2004, to
      October 31, 2005. Data on medications used and number of hemodialysis procedures
      and hospitalizations were collected. On average, 2.8+/-0.4 hemodialysis
      procedures per patient a week were carried out. Expenditures for hemodialysis
      procedures were 38 094.12+/-5003.17 litas (11,041 euros) per patient per year,
      and this accounted for 63% of all expenditures for hemodialysis patient.
      Hospitalization rate was 1.4+/-1.8 per patient a year; expenditures for
      hospitalizations were 1538.4+/-1941 litas (446 euros) per patient a year (3% of
      all expenditures for hemodialysis patients). The mean number of drugs prescribed
      per patient monthly was 7.7+/-2.17 including 2.12+/-1.6 antihypertensive
      medications. The total costs of drugs reimbursed by State Patients' Fund were
      20,639.82+/-15,439.3 litas (5983 euros) per patient per year, of which 92% was
      spent on erythropoietin and intravenous iron. The average expenditures for health
      insurance of hemodialysis patients were 60,272.35+/-16,624.18 litas (17,470
      euros) per patient a year. One patient had to pay 1.9+/-1.6 litas for medications
      per day and 699.71+/-583.6 litas (203 euros) per year. The comparison of the data
      gathered in 2001 and 2005 revealed an increase in the total expenditures for
      hemodialysis patients due to increase in the expenditures for hemodialysis
      procedures and medications.

PMID- 17551284
TI  - [Evaluation of bone mineral density and its importance for hemodialysis
      patients].
AB  - The aim of the study was to determine the changes in bone mineral density in
      hemodialysis patients and to evaluate their correlation with disorders of calcium
      phosphate metabolism. PATIENTS AND METHODS: Data of 82 patients on chronic
      hemodialysis were analyzed. The patient group consisted of 40 (48.8%) men and 42
      (51.2%) women. Clinical and laboratory data were collected from medical records.
      Bone mineral density was measured by ultrasound (Sahara Hologic densitometer) in
      the heel area. RESULTS: The mean age of the patients was 60.13+/-16.02 years.
      Mean T score was 1.7+/-1.19, mean Z score was 1.076+/-1.2, and mean bone mineral
      density was 0.393+/-0.0 g/cm2. Women had significantly lower bone mineral density
      than men (0.361 g/cm2 and 0.425 g/cm2, respectively; P=0.006). Normal bone
      mineral density, when T score was -1 and more, was observed only in 23 (28%)
      patients. More than one-third (n=37, 45.1%) of patients were classified as
      osteopenic (T score between -2.5 and -1) and 22 (26.8%) patients as osteoporotic
      (T score less than -2.5). Patients with normal bone mineral density were
      significantly younger than those with decreased bone mineral density (54.7+/
      15.48 years vs. 58.76+/-15.76 years and 68.09+/-14.5 years, respectively;
      P<0.05). Laboratory parameters reflecting calcium-phosphate metabolism did not
      differ between the groups. A statistically significant correlation was observed
      between T score, bone mineral density and age (-0.328, P=0.03 and -0.301,
      P=0.007, respectively), body weight (0.27, P=0.014 and 0.339, P=0.002,
      respectively), and level of parathyroid hormone (-0.322, P=0.003 and -0.286,
      P=0.01, respectively). CONCLUSIONS: In our study, bone mineral density lower than
      normal was observed in more than half of hemodialysis patients. Low bone mineral
      density in hemodialysis patients correlated with age, gender, lower body weight,
      and higher level of parathyroid hormone.

PMID- 17551285
TI  - [Survival of hemodialysis patients in Lithuania (data from all hemodialysis
      centers in the 1998-2005 cohort)].
AB  - BACKGROUND: There is no any official renal registry in Lithuania, so in order to
      know the exact demographic statistics of patients on hemodialysis, we started to
      collect data since 1996. The aim of the study was to estimate the survival rate
      of hemodialysis patients and its dynamics, to compare survival in different
      groups of sex, age, primary renal disease, and to compare to survival of dialysis
      patients in Europe. MATERIAL AND METHODS: We analyzed the data of all patients
      who started hemodialysis in Lithuania between January 1, 1998, and December 31,
      2005. The information was obtained from medical documentation. The total survival
      rate was estimated using the Kaplan-Maier method. RESULTS: During the study
      period, 2418 patients started hemodialysis (51.7% of males, 48.3% of females).
      Their mean age at the beginning of treatment was 56.19+/-16.12 years. Death
      occurred in 792 patients. The main cause of death was cardiovascular events,
      accounting for 32.3%. The total survival rate of hemodialysis patients in
      Lithuania at 1 year was 79.97%; at 2 years, 69.18%; at 5 years, 49.97%; at 7
      years, 38.3%. Males lived longer than females (log rank P<0.05), but the mean age
      of females was greater, and survival rate adjusted for age did not differ between
      the groups. The highest survival rate was in the youngest group (0-19 years old),
      the lowest - in patients older than 75 years. Diabetic patients lived shorter
      than nondiabetic patients (log rank P<0.00001). Although patients who start
      hemodialysis have become older and their survival has been improving, in the 1998
      2002 cohort survival was lower as compared to overall survival of patients on
      dialysis in European countries participating in ERA-EDTA registry. CONCLUSION:
      Survival of hemodialysis patients in Lithuania in the 1998-2005 cohort depended
      on age and primary renal disease and despite aging of population on hemodialysis
      has been improving.

PMID- 17551286
TI  - [Quality of life and depression in renal transplant patients].
AB  - The objective of this study was to examine the factors affecting quality of life
      in renal transplant patients and to evaluate the association between depression
      and quality of life. MATERIAL AND METHODS: A study was carried out in 61 renal
      transplant patients. Health-related quality of life was evaluated using the
      Medical Outcomes Study 36-item Short Form (SF-36) questionnaire. Depression was
      measured using the Beck's Depression Inventory (BDI). RESULTS: Twenty percent of
      the subjects had a BDI score higher than 15. The BDI score correlated inversely
      with these quality-of-life domains: physical functioning (r=-0.691, P<0.001),
      limitations in physical activities because of physical problems (r=-0.428,
      P=0.001), bodily pain (r=-0.662, P<0.001), and limitations in usual role
      activities because of emotional problems (r=-0.319, P<0.001). The BDI score also
      correlated with age (r=0.44, P<0.001) and serum creatinine level (r=0.453,
      P<0.001). Subjects with BDI score higher than 15 were significantly older
      (51.40+/-11.35 years vs. 42.64+/-10.89 years, P<0.05), they had higher serum
      creatinine levels (215.7+/-82.63 micromol/L vs. 153.2+/-50.6 micromol/L, P<0.05),
      lower bodily pain score (39.7+/-21.44 vs. 72.32+/-19.0, P<0.001), and lower score
      in limitations in usual role activities because of emotional problem (36.6+/
      33.23 vs. 67.36+/-37.83, P<0.05). CONCLUSIONS: Depression was associated with a
      lower quality of life in four domains. Patients with depression were older and
      had a worse graft function.

PMID- 17551287
TI  - [Clinical effect of induction therapy with monoclonal antibodies after deceased
      donor kidney transplantation (an experience from Vilnius Center)].
AB  - We aimed at evaluating the impact of monoclonal antibodies on immune response
      against deceased-donor kidney transplant: the frequency and severity of acute
      rejection episodes during first 3 months after transplantation and graft loss
      rate at one year. The frequency of infectious complications during the first 6
      months after transplantation and patient survival rate during one year were also
      analyzed. Our study included 187 deceased-donor renal transplants performed in
      Santariskes Clinics of Vilnius University Hospital from January 2000 to December
      2004. Study group (Group 1) consisted of 66 patients who received additional
      induction therapy with monoclonal antibodies (31 patients treated with
      basiliximab and 35 patients treated with daclizumab); 121 patients in control
      group (Group 2) were treated only with conventional immunosuppression. Both
      groups received maintenance immunosuppressive therapy including cyclosporine,
      mycophenolate mofetil, and steroids. Patient and graft survival rates were
      calculated by Kaplan-Meier method. There were no significant differences in the
      age of patients, HLA mismatches, percentages of highly sensitized patients (panel
      reactive antibody level more than 50%), and repeated transplantation between both
      groups. The incidence of biopsy-proven acute rejection during the first 3 months
      after transplantation was significantly lower in Group 1 than in Group 2 (15.2%
      vs. 28.1%, P<0.05). There were no significant differences in patient survival
      rates (95.5% vs. 90.1%) between two groups at one year, but graft survival rate
      was significantly higher in Group 1 than in Group 2 (94.0% vs. 77.0%, P<0.05).
      The proportion of patients with infectious complications during the first 6
      months after transplantation was significantly lower in study group than in
      control group (33.3% vs. 49.6%, P<0.05). Therefore, induction therapy with
      monoclonal antibodies reduced the incidence and severity of acute rejection in
      early period after transplantation and led to higher graft survival rate. The
      lower frequency of infectious complications was observed in patients receiving
      induction therapy with monoclonal antibodies.

PMID- 17551288
TI  - [Parallels in development of hemodialysis service and kidney transplantations in
      Lithuania during 1996-2005].
AB  - The aim of our study was to evaluate the changes in hemodialysis service, main
      demographic characteristics of hemodialysis patients in Lithuania during 1996
      2005, and their correlation with the number of recipients on the kidney waiting
      list. During the study period, we annually visited all hemodialysis centers in
      Lithuania and collected data about all hemodialysis patients. There was a sharp
      increase in the number of hemodialysis centers (from 17 to 43), hemodialysis
      stations (from 25 to 100 per million population, P<0.001), hemodialysis patients
      (from 60 to 312 per million population, P<0.001), and new hemodialysis patients
      (from 54.3 to 95 per million population, P<0.01). The mean age of hemodialysis
      patients increased from 47.2+/-16.1 years in 1996 to 58.8+/-15.6 years in 2005
      (P<0.001). Hemodialysis population became older. The percentage of patients aged
      more than 60 years increased from 22.8% to 53.2% (P<0.001) and aged more than 70
      years from 5.4% to 24.4% (P<0.001). The frequency of chronic glomerulonephritis
      as underlying disease of end-stage renal disease decreased from 54.5% in 1996 to
      21.1% in 2005 (P<0.001). There was an increase in the percentage of patients in
      whom end-stage renal disease was caused by diabetic (from 7.1% to 19.2%, P<0.01)
      and hypertensive nephropathies (from 3.1% to 13.9%, P<0.05) and chronic
      pyelonephritis (from 11.2% to 17.9%, P<0.01). The percentage of recipients on the
      kidney waiting list decreased from 71.4% in 1996 to 21.1% in 2005. In summary,
      during the last 9 years, hemodialysis service in Lithuania significantly
      expanded. The number of hemodialysis patients was continuously rising with
      predominance of diabetic, hypertensive, and elderly patients. Diabetic
      nephropathy, chronic glomerulonephritis, and pyelonephritis were the main
      underlying diseases of end-stage renal disease in hemodialysis patients in 2005.
      The percentage of recipients on the kidney waiting list decreased probably
      because of the rise in the number of elderly patients and patients with diabetes
      mellitus in Lithuanian hemodialysis population.

PMID- 17551289
TI  - [Reactivation of cytomegalovirus infection after kidney transplantation in Kaunas
      University of Medicine Hospital during the period of 2000-2006].
AB  - Cytomegalovirus infection has been associated with increased morbidity and
      mortality after transplantation and with diminished graft survival. After
      transplantation, more than 75% of solid organ transplant patients are newly
      infected with cytomegalovirus, or latent cytomegalovirus infection may be
      reactivated. The objective of our study was to evaluate reactivation rate of
      cytomegalovirus infection after kidney transplantation in Kaunas University of
      Medicine Hospital and its relation to anticytomegalovirus prophylaxis. A
      retrospective review of all kidney transplants performed between May 2000 and
      December 2006 was conducted. We analyzed the prevalence of cytomegalovirus in the
      groups of donors and recipients, and risk categories were defined for
      cytomegalovirus infection/disease in transplant patients. During this period, a
      total of 93 transplantations were performed in 56 men (60.2%) and 37 women
      (39.8%). The mean age of recipients was 41.04+/-12.74 years. There were 33
      (68.7%) men and 15 (31.3%) women in the group of donors; their mean age was
      39.49+/-14.81 years. Patients at high risk for the development of cytomegalovirus
      infection/disease were defined as those who had donor-positive/recipient-negative
      serostatus (D+/R-), and they made up 5.4% of all patients. Intermediate-risk
      patients with cytomegalovirus infection (D+/R+ and D-/R+) accounted for 73.1% and
      15.1% of all recipients, respectively; 6.4% of patients were at low risk (D-/R-).
      Anti-cytomegalovirus prophylaxis with i/v ganciclovir was given during the period
      of hospitalization in all cases, except when there was a D-/R- combination, or
      when the transplant was removed in the early period after transplantation. The
      reactivation of cytomegalovirus infection was observed in 23 patients (24.7%). We
      have observed 41 episodes of cytomegalovirus infection, but during this period,
      no patient developed cytomegalovirus disease that might cause lethal outcome.

PMID- 17551290
TI  - [Creation of arteriovenous fistulas for chronic hemodialysis in Kaunas University
      of Medicine Hospital during 2005-2006].
AB  - We analyzed case histories of 299 patients with end-stage renal failure,
      hospitalized in our hospital for the creation of an arteriovenous fistula for
      chronic hemodialysis. Demographic data, indications for the creation of an
      arteriovenous fistula, laboratory data, and duration of hospitalization were
      analyzed. RESULTS. The highest number of arteriovenous fistulas was created in
      the patients from Kaunas region (48.04%); 23.74% of patients were diabetic.
      Primary native fistula was created in 61.2% of patients, secondary in 36.46% of
      cases, and in 2.34% of patients, permanent catheters were inserted. Preoperative
      Doppler ultrasonography of vessels was performed in 18.73% of patients. The mean
      duration of hospitalization of all patients was 30.61+/-4.3 days (29.05+/-5.2
      days in the Clinic of Nephrology and 35.53+/-5.52 days in the Clinic of
      Endocrinology). During this period, patients were waiting for operation in an
      average of 16.78+/-6.4 days and 14.78+/-4.87 days for maturation of fistula.

PMID- 17551291
TI  - [Cytomegalovirus infection in kidney transplant recipients in Santariskes Clinics
      of Vilnius University Hospital].
AB  - Between January 2000 and December 2006, 318 kidney transplants were performed in
      our unit. Cytomegalovirus infection in transplanted patients causes both direct
      and indirect effects on other organ systems, including acute allograft rejection
      and decreased graft and patient survival. The aim of our study was to evaluate
      the incidence of cytomegalovirus infection after kidney transplantation, the
      treatment strategies, and the impact of cytomegalovirus infection on allograft
      function and survival. Those patients who at least once were treated for
      cytomegalovirus infection were assigned to the study group (n=102). The control
      group included the remaining patients (n=216) in whom kidney transplantation was
      performed between January 2000 and December 2006. The mean age of the recipients
      in both groups was 39.8+/-12.8 years (range 15-60) and 38.5+/-12.6 years (range 7
      66), respectively; retransplantations and acute allograft rejections were more
      common in the group treated for cytomegalovirus infection: 13 (12.7%) vs. 18
      (8.3%) and 55 (53.9%) vs. 103 (47.2%), respectively. Between January 2000 and
      December 2006, the total number of cytomegalovirus infection episodes was 167.
      The greatest number of cytomegalovirus infection episodes occurred during the
      first 1-3 months after transplantation and accounted for 27.5%; during 3-6
      months, 17.4%; during 6-12 months, 18.6%. Serum creatinine levels were higher in
      our study group. Cytomegalovirus infection manifested as pneumonitis in 26.5% and
      as gastrointestinal tract disorders in 9.8% of cases; 3.9% of patients were
      treated for encephalitis. Patients in the study group reported more frequently
      other infections: bacterial infections, 66 (64.7%) vs. 116 (53.7%); virus
      infections, 2 (2%) vs. 3 (1.4%); and mixed bacterial-virus infections, 8 (7.8%)
      vs. 4 (1.9%). The number of patients who did not experience any infection was
      higher in control group: 26 (25.5%) vs. 93 (43.1%). Death from cytomegalovirus
      infection occurred in 15 (14.7%) of the 102 patients in the study group.

PMID- 17551292
TI  - [Fabry's disease: a clinical case and literature review].
AB  - Fabry's disease is a congenital disorder of glycosphingolipid metabolism with an
      X-linked recessive inheritance, presenting with typical symptoms of pain crises,
      acroparesthesias, cutaneous and mucosal angiokeratomas, hypohidrosis, heart and
      kidney lesions, and other symptoms, which are described below. From 2001, this
      disease is one of inborn errors of metabolism in which enzyme replacement therapy
      is applied very effectively. Two atypical forms of the disease were discovered,
      and the first surveys were done revealing that the incidence of Fabry's disease
      can be much more higher than it was considered before. Not only pediatricians can
      encounter with these patients in their practice, but also family doctors,
      nephrologists, cardiologists, neurologists, and physicians of other specialties.
      A clinical case of Fabry's disease is described, and actual issues of diagnostics
      and treatment of Fabry's disease are discussed. In spite of very typical
      symptoms, delayed diagnosis was made: after the first investigation of alpha
      galactosidase A activity in dry blood sample, diagnosis of Fabry's disease was
      rejected; only after lysosomal enzyme activity assay in heparinized blood
      leukocytes, this diagnosis was confirmed.

PMID- 17551293
TI  - [Living donor kidney transplantation after resection of carcinoma].
AB  - The aim of the article is to present a case of incidental renal cell carcinoma in
      living donor kidney, which was successfully transplanted following resection of
      carcinoma. A 38-year-old female recipient with end-stage renal disease was on
      maintenance hemodialysis for 4 months. The donor was her mother aged 60 years.
      Preoperative renal scintigraphy, aortography, and ultrasound examination
      confirmed good function of donor kidneys. The reason for transplanting the right
      kidney was slightly diminished phase of secretion revealed by scintigraphy. On
      February 14, 2001, mother's right kidney was removed, and after hypothermic
      perfusion, yellowish nodule in the upper part of the kidney was found.
      Microscopic investigation of the resected material revealed renal clear cell
      carcinoma. Decision on complete tumor resection was based on the findings of
      microscopic examination. After suturing the resected segment, mother's kidney was
      transplanted successfully. The postoperative course was normal in the donor and
      the recipient as well. Cyclosporine A was replaced with Rapamune. No tumor
      recurrence was seen for more than 6 years after transplantation, and transplant
      function was normal.

PMID- 17551294
TI  - [Chronic graft-versus-host disease presenting as nephrotic syndrome after
      allogenic hematopoietic stem cell transplantation].
AB  - Complications of allogenic hematopoietic stem cell transplantation that occur in
      the first 100 days are considered early and those that begin 100 days after are
      considered late complications. Chronic graft-versus-host disease is the most
      common late complication of allogenic hematopoietic cell transplantation, which
      occurs in 60-80% of long-term survivors and causes significant morbidity and
      mortality. It is well known that it affects primarily the skin, mucous membranes,
      cells in the gastrointestinal tract and liver. The kidneys are not considered a
      target organ for chronic graft-versus-host disease in humans, although renal
      involvement in patients with chronic graft-versus-host disease, presenting as
      nephrotic syndrome, has been reported in patients who underwent allogenic
      transplantation. We present a case of chronic graft-versus-host disease that
      manifested as nephrotic syndrome after hematopoietic cell transplantation
      performed 3 years ago. Kidney biopsy revealed membrane nephropathy. Treatment
      with cyclosporine and methylprednisolone significantly reduced albuminuria.

PMID- 17551295
TI  - Chronic genitourinary and gastrointestinal toxicity of prostate cancer patients
      undergoing pelvic radiotherapy with intensity-modulated versus 4-field technique.
AB  - PURPOSE: To compare chronic GU and GI toxicity of pelvic radiotherapy delivered
      using intensity-modulated radiotherapy (IMRT) versus conventional 4-field
      technique. METHODS: The records of consecutive prostate cancer patients receiving
      RT at a single institution with a minimum follow-up of 120 days were reviewed; 48
      of these patients received a prostate boost preceded by pelvic radiotherapy
      (PRT), 14 with IMRT (IM-PRT), and 34 with 4-field (4F-PRT). Dosimetric endpoints
      for the bladder, rectum, composite, and target for the PRT plans were compared
      using the 2-tailed t test. Late RTOG GU and GI toxicity were compared using the
      chi test. Ordered logit regression analyses were performed using all major
      patient, disease, and treatment factors as covariates. RESULTS: IM-PRT
      demonstrated superior bladder and rectum dosimetric endpoints over 4F-PRT for the
      PRT portion of the treatment and for the composite treatment at the expense of
      higher target inhomogeneity in the PRT portion of the treatment plan. Late GU
      toxicity was significantly lower in the IM-PRT group (P < 0.001), whereas late GI
      toxicity was similar in both groups (P = 0.44). When considering a similar follow
      up interval in both groups, however, the difference in GU toxicity only reached a
      trend (P = 0.10). The regression analyses showed that no factor, including IMRT,
      reached significance in predicting GU or GI toxicity. CONCLUSION: Use of pelvic
      IMRT for prostate cancer patients was not associated with reduction of late GI
      toxicity but was associated with a small reduction of late GU toxicity. This
      reduction of late GU toxicity warrants further exploration in consortium studies.

PMID- 17551296
TI  - Effects of sorafenib on symptoms and quality of life: results from a large
      randomized placebo-controlled study in renal cancer.
AB  - INTRODUCTION: The aim of the current study was to determine the impact of
      treatment with sorafenib versus placebo on renal cancer symptoms and quality of
      life (QOL). METHODS: Symptoms were measured by the Functional Assessment of
      Cancer Therapy (FACT)-Kidney Cancer Symptom Index (FKSI) and QOL by the FACT
      General (FACT-G). The FACT-G and FKSI were administered at baseline and day 1 of
      each cycle. Statistical analyses used a random coefficient model over 5 cycles
      for total score and individual items, using Memorial Sloan Kettering Risk Score
      (MSK) and treatment as factors and baseline score and treatment time as
      covariates. FKSI correlation to survival was based on a Cox proportional hazards
      model adjusting for treatment, age, and MSK. RESULTS: At baseline and over time,
      there were no differences in mean scores for either the FACT-G or FKSI between
      the sorafenib and placebo groups. FKSI single-item analysis showed that sorafenib
      treated patients reported significantly fewer symptoms and concerns versus
      placebo (eg, cough (P < 0.0001), fevers (P = 0.0015), shortness of breath (P < or
      = 0.0312), ability to enjoy life (P = 0.0119), and worry that condition will get
      worse (P = 0.0004). Only concern about treatment side effects favored placebo (P
      < 0.0001). Baseline FKSI total score predicted overall survival (P < 0.0001).
      CONCLUSIONS: Sorafenib shows clinical benefit without adversely impacting overall
      QOL and has a positive impact on some individual symptoms and concerns. These
      findings are consistent with other clinical results from this trial of advanced
      renal cell carcinoma patients treated with sorafenib, which included
      significantly greater progression-free survival and low risk for treatment
      limited toxicities.

PMID- 17551297
TI  - Dosimetry of an extracapsular anulus following permanent prostate brachytherapy.
AB  - PURPOSE: Recent studies have suggested that extracapsular brachytherapy treatment
      margins correlate with biochemical control. It is likely that volumetric
      geographic dosimetric parameters will be more robust than selected radial
      measurements. Accordingly, we evaluated extracapsular volumetric dosimetric
      parameters in low-risk patients. MATERIALS AND METHODS: A total of 263 low-risk
      prostate cancer patients randomized to Pd-103 versus I-125 were implanted with a
      brachytherapy target volume consisting of the prostate with a 5-mm periprostatic
      margin. The median follow-up was 4.2 years. All patients were implanted at least
      3 years prior to analysis. Within 2 hours of implantation, an axial CT was
      obtained for postimplant dosimetry. A 5-mm three-dimensional periprostatic anulus
      was constructed around the prostate and evaluated in its entirety and in 90
      degrees segments. Prostate and anular dosimetric parameters consisted of
      V100/V150/V200 and D90. Biochemical progression-free survival (bPFS) was defined
      as a PSA < or =0.50 ng/mL after nadir. RESULTS: The Pd-103 and I-125 arms were
      well-matched in terms of clinical, biochemical, and pathologic presentation. Six
      year bPFS was 96.8% versus 99.2% for I-125 versus Pd-103 (P = 0.149). The most
      recent median posttreatment PSA was <0.04 ng/mL for both isotopes. No significant
      differences in postoperative anular doses were discerned between bPFS and failed
      patients. CONCLUSIONS: A postimplant 5-mm, three-dimensional periprostatic anulus
      provides substantial information regarding dosimetric coverage. However, with a
      median follow-up of 4.2 years, such volumetric and geographic parameters have not
      proven useful in predicting biochemical outcome in low-risk patients.

PMID- 17551298
TI  - Activity of weekly paclitaxel in advanced hormone-refractory prostate cancer.
AB  - OBJECTIVE: We evaluated efficacy and toxicity of weekly paclitaxel in metastatic
      hormone-refractory prostate cancer (HRPC). MATERIALS AND METHODS: Patients
      received weekly paclitaxel 80 mg/m2 by 1-hour intravenous infusion. A course of
      therapy consisted of 6 weekly treatments and 2 weeks rest. PSA response was
      defined as a PSA decrease not less than 50%, maintained for 4 weeks with stable
      or improved performance status. RESULTS: The study enrolled 43 patients with
      metastatic HRPC diagnosed a median of 10.5 months before. Median age was 69 years
      (range, 58-86 years). Five had previous radioisotopes treatment for bone pain, 15
      had previous treatment of metastatic hormone-refractory disease, mainly
      estramustine. The median number of weeks of therapy delivered each patient was 8
      (range, 1-24 weeks; cumulative, 369 weeks). PSA response was registered in 13
      patients of 36 evaluable for PSA response (36.1%; 95% confidence interval [CI],
      20.8-53.8), with a median duration of 4.2 months. Among 16 patients evaluable for
      objective response, 5 partial responses (31.2%; 95% CI, 11.0-58.7) and 9 stable
      diseases were registered. Eleven (42.3%) of 26 patients presenting with cancer
      related symptoms had improvement. Median survival time was 12.8 months (95% CI,
      10.1-15.5) Therapy was associated with acceptable hematological toxicity (anemia
      grade 3, 16%; neutropenia grade 3-4, 12%) and moderate nonhematologic toxicities
      (thrombosis/embolism 10%; fatigue all grades, 60%). CONCLUSION: Docetaxel every 3
      weeks is the standard of care for metastatic HRPC, but our results suggest some
      activity and an acceptable toxicity of weekly paclitaxel.

PMID- 17551299
TI  - A randomized study of involved-field irradiation versus elective nodal
      irradiation in combination with concurrent chemotherapy for inoperable stage III
      nonsmall cell lung cancer.
AB  - BACKGROUND: Radiation dose escalation is limited by the high incidence of
      pulmonary and esophageal toxicity, leading to calls for the omission of elective
      nodal irradiation (ENI) and the willingness to use involved-field irradiation
      (IFI) in patients with nonsmall cell lung cancer (NSCLC). METHODS AND MATERIALS:
      A total of 200 eligible patients with inoperable stage III NSCLC were treated
      with concurrent chemoradiotherapy and randomized into either an IFI or ENI arm. A
      total of 4 to 6 cycles of cisplatin-based chemotherapy were delivered, and
      concurrent radiotherapy was started after the second cycle of chemotherapy. Three
      dimensional conformal radiotherapy was delivered in once-daily fractions of 1.8
      to 2 Gy to 68 to 74 Gy for IFI or 60 to 64 Gy for ENI. RESULTS: Patients in the
      IFI arm achieved better overall response rate (90% vs. 79%, P = 0.032) and better
      5-years local control rate (51% vs.36%, P = 0.032) than those in the ENI arm. The
      radiation pneumonitis rate in patients with IFI was lower than in patients with
      ENI (17% vs. 29%, P = 0.044), and similar trends appeared in the radiation
      esophagitis, myelosuppression, and radiation pericarditis between 2 study arms,
      although not significantly. The 1-, 2-, and 5-year survival rates were 60.4%,
      25.6%, and 18.3% for the ENI arm and 69.9%, 39.4%, and 25.1% for the IFI arm,
      respectively. Only the 2-year survival rates were statistically significant (P =
      0.048). CONCLUSION: IFI arm achieved better overall response and local control
      than ENI arm, and it allowed a dose of 68 to 74 Gy to be safely administered to
      patients with inoperable stage III NSCLC. Outcome improvement can be expected by
      conformal IFI combined with chemotherapy for stage III NSCLC.

PMID- 17551300
TI  - Oral versus intravenous administration of vinorelbine as a single agent for the
      first-line treatment of metastatic nonsmall cell lung carcinoma (NSCLC): A
      randomized phase II trial.
AB  - OBJECTIVES: Many patients with metastatic nonsmall cell lung carcinoma (NSCLC)
      cannot tolerate intravenous chemotherapy. Orally active agents would be more
      convenient and thus could improve their quality of life. METHODS: A total of 189
      patients were randomized 2:1, 181 patients received treatment, 120 PO and 61 IV
      vinorelbine, 158 patients had stage IV and 31 stage IIIB disease. Among patients
      who received PO vinorelbine, the median age was 72 years, 62% were males; the
      Karnofski Performance Status (KPS) was 80-100 in 71%. These compare with a median
      age of 70 years, 56% male, and KPS of 80-100 in 65% of patients who received IV
      vinorelbine. Oral vinorelbine 60 mg/m2 was to be dose-escalated to 70 mg/m2 after
      the initial 3-weekly doses if there was no unacceptable toxicity. Intravenous
      vinorelbine was to be given 30 mg/m2 weekly. RESULTS: Five patients (4%) on PO
      and 8 (13%) on IV vinorelbine had a confirmed partial response, 56 (44%) and 29
      (46%) had stable disease, respectively. Median time-to-disease-progression was
      16.6 weeks (PO) versus 23.9 weeks (IV), and the median survival was 26 weeks (PO)
      versus 40.9 weeks IV vinorelbine. Median survival on PO vinorelbine for patients
      with KPS 60-70 was 8.3 weeks versus 43 weeks (IV). On PO vinorelbine 59 patients
      (57%) were dose escalated, 9 (7.5%) were dose reduced, and 10 (8.3%) did not
      receive PO vinorelbine at week 4. Pharmacokinetic studies confirmed PO
      vinorelbine exposure was significantly less than IV exposure. CONCLUSION: The
      inability to escalate the dose of PO vinorelbine above 60 mg/m2 weekly resulted
      in inferiority to IV vinorelbine at 30 mg/m2 weekly, especially in patients with
      poor performance status.

PMID- 17551301
TI  - Favorable genetic polymorphisms predictive of clinical outcome of
      chemoradiotherapy for stage II/III esophageal squamous cell carcinoma in
      Japanese.
AB  - OBJECTIVES: This study was performed to find the genetic factors predictive of
      clinical outcome to a 5-fluorouracil (5-FU)/cisplatin (CDDP)-based
      chemoradiotherapy (CRT) in Japanese patients with locally advanced esophageal
      squamous cell carcinoma (ESCC). MATERIALS AND METHODS: Thirty-one patients with
      stage I-IVa ESCC (I/II/III/IVa = 7/7/14/3) were enrolled in this study. One
      course of treatment consisted of protracted venous infusions (PVIs) of 5-FU (400
      mg/m2/24 hours for days 1-5 and 8-12), CDDP (40 mg/m2/3 hours on days 1 and 8)
      and radiation (2 Gy/d on days 1-5, 8-12, and 15-19), and a 2nd course was
      successively repeated after a 2-week interval. A total of 8 measurements of the
      plasma concentration of 5-FU were made using high performance liquid
      chromatography. Genetic polymorphisms examined herein included those in the genes
      coding thymidylate synthase (TS), glutathione S-transferase P1 (GSTP1), multidrug
      resistant transporter MDR1/P-glycoprotein, and intercellular adhesion molecule-1,
      and in a circadian rhythm-relating gene, CLOCK. RESULTS: The CR rate depended on
      stage (P = 0.001), but the analysis was not sufficiently powered to reach a level
      of statistical significance for the 2-year survival rate (P = 0.061). For stage
      II/III patients, to have 2 or 3 polymorphisms of 3R/3R of 5'-TSER, a 6 bp of 3'
      TSUTR, and GSTP1-Ile105Val resulted in an extensively longer survival (P =
      0.020), although no difference was found between 2 groups, with respect to the
      plasma concentrations of 5-FU and clinicopathologic characteristics. CONCLUSIONS:
      The prognostic index may allow predictions of the clinical outcome of a 5-FU/CDDP
      based CRT in stage II/III ESCC patients.

PMID- 17551302
TI  - Chemotherapy and high dose radiotherapy followed by resection for locally
      advanced nonsmall cell lung cancers.
AB  - OBJECTIVES: For locally advanced but technically operable nonsmall cell lung
      cancer (NSCLC), neoadjuvant chemoradiotherapy is frequently used. Ideal
      radiotherapy dose in this context is unclear. MATERIALS AND METHODS: Twenty-six
      NSCLC patients with N2 disease were retrospectively reviewed. All received
      preoperative concurrent platinum-based chemoradiotherapy. Gross tumor volumes
      received a median of 58 Gy (range, 50-60 Gy). RESULTS: Two patients experienced
      major complications and died, resulting in a postoperative mortality rate of
      7.7%. Three patients (11.5%) had minor complications. Pathologic specimens
      revealed downstaging in 76.9% of patients. The pathologic complete response (CR)
      rate was 34.6%. Downstaging of nodes was observed in 20 of 26 patients. With a
      median follow-up of 18.3 months, the 1- and 3-year actuarial survival rates were
      80.2% and 45.7%, respectively. The 1- and 3-year actuarial disease-free survival
      (DFS) rates were 76.9% and 37.3%, respectively. Patients experiencing mediastinal
      downstaging had better DFS rates, relative to patients that did not (18-month DFS
      = 79.2% vs. 0%; P = 0.0001). Differences in RT dose (50-60 Gy) and types of
      chemotherapeutic regimens did not significantly impact pathologic downstaging
      rates, CR rates, DFS, or survival. DISCUSSION: Neoadjuvant chemotherapy with high
      dose concurrent RT is well tolerated and results in favorable outcomes.

PMID- 17551303
TI  - Pathology and FDG PET correlation of residual lymph nodes in head and neck cancer
      after radiation treatment.
AB  - BACKGROUND: This study determines if postradiotherapy [18F]fluorodeoxyglucose
      positron emission tomography (FDG PET) can predict the pathology status of
      residual cervical lymph nodes in patients undergoing definitive radiotherapy for
      head and neck squamous cell carcinoma (HNSCC). METHODS: Patients with stage N2 or
      higher HNSCC underwent PET and CT imaging after definitive radiotherapy. Patients
      with radiographically persistent lymphadenopathy underwent either neck dissection
      or fine needle aspiration (FNA) of the lymph nodes under ultrasound guidance. PET
      scan results were correlated with the pathologic findings of the residual
      lymphadenopathy. RESULTS: Twenty-four hemi-necks in 23 patients with residual
      lymphadenopathy had neck dissection or FNA. The pathology correlated strongly
      with the post-RT FDG PET studies. All patients with a negative post-RT FDG PET
      and those with a maximum standardized uptake value (SUVmax) of less than 3.0 in
      the post-RT FDG PET were found to be free from residual viable tumor. Using a
      SUVmax of less than 3.0 as the criterion for a negative FDG PET study, the
      sensitivity, specificity, positive predictive value, and negative predictive
      value were 100%, 84.2%, 62.5%, and 100%, respectively. CONCLUSIONS: A negative
      post-RT FDG PET is very predictive of negative pathology in the residual lymph
      node after definitive radiotherapy for advanced HNSCC. A prospective clinical
      trial is warranted to determine if neck dissection can be withheld in these
      patients.

PMID- 17551304
TI  - Correlation between saliva production and quality of life measurements in head
      and neck cancer patients treated with intensity-modulated radiotherapy.
AB  - PURPOSE: To investigate the strength of correlation between measured saliva flow
      rates and various toxicity endpoints commonly used in head and neck cancer (HNC)
      treatment. MATERIALS AND METHODS: All patients enrolled in a phase II study using
      intensity modulated radiotherapy (IMRT) for HNC treatment underwent whole mouth
      saliva flow measurements (stimulated and unstimulated). They were also assessed
      for salivary gland toxicity using Radiation Therapy Oncology Group (RTOG) late
      toxicity grading and 9 items representing patient-graded toxicities from 2
      questionnaires (Xerostomia questionnaire and University of Washington quality of
      life). For each patient, saliva flow rates and quality of life (QOL) data were
      collected preradiotherapy (RT) and at 3 intervals post-RT (3, 6, and 12 months).
      RESULTS: A total of 188 sets of coregistered data were obtained for 47 patients
      over a period of approximately 4 years. Saliva production and mean QOL dropped
      significantly immediately after RT, but there was a statistically significant
      recovery in both parameters between 3- and 12-month post-RT. By 12 months, post
      RT the mean QOL scores had returned to pre-RT baseline, although mean stimulated
      saliva production remained 58% below baseline. CONCLUSION: Patients with HNC
      treated with IMRT experienced a small drop in QOL which recovered to baseline by
      12 months post-RT. There was no statistically significant correlation seen
      between global health-related QOL scores and stimulated saliva production rates
      in the post-RT period.

PMID- 17551305
TI  - Docetaxel plus gemcitabine in recurrent and/or metastatic squamous cell carcinoma
      of the head and neck: a phase II multicenter study.
AB  - OBJECTIVES: This phase II study was conducted to assess the efficacy of docetaxel
      plus gemcitabine in locally recurrent and/or metastatic squamous cell carcinoma
      of the head and neck. PATIENTS AND METHODS: Forty patients with pharynx or larynx
      cancer were included and treated with an intravenous infusion of docetaxel 75
      mg/m2 on day 8 and gemcitabine 1000 mg/m2 day 1 and day 8 every 3 weeks for 6
      cycles. RESULTS: Among the 40 patients included, 17 had metastatic disease and 18
      had received prior chemotherapy. Thirty-two patients were assessable for
      response. The overall response rate was 20.0% (95% confidence interval [CI], 9.0%
      35.7%), with 8 (20.0%) partial responses. Thirteen patients (32.5%) had stable
      disease, whereas 11 patients (27.5%) had progressive disease. The median response
      duration was 6.5 months (95% CI, 5.8-7.2). Grade 3 or 4 neutropenia was observed
      in 18 patients (45.0%). Three treatment-related deaths due to infection were
      reported. CONCLUSION: The docetaxel and gemcitabine combination is an active
      treatment of recurrent or metastatic head and neck cancer. However, this regimen
      is associated with a high hematologic toxicity. A new schedule of administration
      must be explored.

PMID- 17551306
TI  - Radiotherapy and concomitant intraarterial cisplatin (RADPLAT) for advanced
      squamous cell carcinomas of the head and neck.
AB  - PURPOSE: Review of the University of Florida experience in treating advanced
      squamous cell carcinomas of the head and neck with concurrent intraarterial
      cisplatin and radiotherapy (RADPLAT). PATIENTS AND METHODS: Thirty-five patients
      with Stage III or IV head and neck squamous cell carcinomas were treated between
      November 2000 and October 2001 with 3 to 4 cycles of weekly intraarterial
      cisplatin (150 mg/m2) and a rapid infusion of the neutralizing agent sodium
      thiosulfate (9 g/m2), followed by a continuous infusion of sodium thiosulfate (12
      g/m2), with concomitant radiotherapy (RT). The primary site was treated with 70
      Gy in 35 fractions with 6 MV photons, and the low neck received 50 to 70 Gy
      depending on nodal involvement. Median follow-up for all patients was 4.06 years;
      median follow-up for living patients was 4.34 years. RESULTS: The 4-year outcomes
      were: local-regional control, 78%; distant metastasis-free survival, 83%; cause
      specific survival, 65%; and survival, 57%. The majority of patients with
      recurrent disease failed at the primary site (73%); the remaining 27% of patients
      with recurrent disease failed only in distant sites. Nine patients required a
      neck dissection after chemoradiation because of suspected residual disease; 2 of
      9 patients had residual tumor in the neck nodes. Severe osteoradionecrosis
      occurred in 26% of patients, and 9 of 35 patients (26%) required a permanent
      gastrostomy. CONCLUSIONS: RADPLAT results in excellent local-regional control and
      survival in patients with advanced squamous cell carcinomas of the head and neck.
      Outcomes from the University of Florida are comparable to those reported by other
      institutions. However, in our limited experience, the likelihood of
      osteoradionecrosis and permanent gastrostomy may be higher than what might be
      anticipated after RT alone or combined with intravenous chemotherapy.

PMID- 17551307
TI  - Cancer patients with markedly elevated B-type natriuretic peptide may not have
      volume overload.
AB  - OBJECTIVES: Elevated B-type natriuretic peptide (BNP) levels are established as a
      marker for volume overload and left ventricular (LV) dysfunction in patients with
      predominately cardiac diseases. Little is known about markedly elevated BNP
      values in patients with multiple comorbidities. METHODS: A total of 99 patients,
      admitted to M. D. Anderson Cancer Center, were identified as having a BNP value
      >1000 pg/mL during the year 2003. Clinical characteristics, including the
      presence of volume overload and sepsis, as well as echocardiographic parameters
      were measured. Principal outcome was defined as 30-day mortality. RESULTS: The
      median BNP (pg/mL) of the group was 2270 (range, 1010-5000), and there was no
      association between elevation of the BNP level and the presence of volume
      overload or LV dysfunction (P = not significant). The large majority of patients
      (n = 71, 72%) had no volume overload and normal or nearly normal LV function (n =
      60, 61%). A majority were also identified as having sepsis (n = 52, 53%). There
      was no echocardiographic parameter that consistently correlated with BNP levels
      or volume overload. There was a highly significant association with sepsis and
      mortality in patients with markedly elevated BNP values, and this conferred a
      2.71-fold increased risk of mortality. CONCLUSIONS: In patients admitted with
      multiple comorbidities and markedly elevated BNP values, there is no significant
      association with clinical evidence of volume overload or LV dysfunction. An
      elevated BNP level in patients with sepsis was significantly associated with
      mortality.

PMID- 17551308
TI  - An association between postoperative radiotherapy for primary breast cancer in 11
      National Surgical Adjuvant Breast and Bowel Project (NSABP) studies and the
      subsequent appearance of pleural mesothelioma.
AB  - OBJECTIVES: Among the minority of patients with pleural mesothelioma and no known
      exposure to asbestos, there have been case reports suggesting a possible
      association with previous radiotherapy. The association between radiotherapy for
      primary breast cancer and the subsequent occurrence of mesothelioma was
      investigated in women entered into 11 National Surgical Adjuvant Breast and Bowel
      Project (NSABP) prospective clinical trials for breast cancer. METHODS: Follow-up
      information was obtained on 22,140 patients entered into 11 NSABP clinical trials
      for treatment of primary breast cancer between 1971 and 1994. Postoperative
      radiotherapy was administered to 9342 patients, mainly after lumpectomy.
      Postlumpectomy patients were treated with radiotherapy just to the ipsilateral
      breast and without regional nodal irradiation. There were 12,798 patients who did
      not have postoperative radiotherapy, and almost all had mastectomy. RESULTS:
      Three pleural mesotheliomas were identified, and all occurred in the ipsilateral
      thorax of the irradiated patients (P = 0.009). All had received postlumpectomy
      breast irradiation for ductal carcinoma in situ. None had a known previous
      exposure to asbestos. CONCLUSIONS: There appears to be a small but statistically
      significant increased risk of developing mesothelioma following radiotherapy
      administered for primary breast cancer. However, in absolute numbers, the risk is
      too small to be considered a contraindication to administering radiotherapy when
      indicated.

PMID- 17551309
TI  - Survival differences observed in metastatic breast cancer patients treated with
      capecitabine when compared with vinorelbine after pretreatment with anthracycline
      and taxane.
AB  - OBJECTIVES: The optimal treatment of metastatic breast cancer patients previously
      treated with anthracycline and taxane is unknown. Common therapeutic alternatives
      include capecitabine and vinorelbine. This retrospective chart review compares
      overall survival following treatment with capecitabine, vinorelbine, or both
      agents sequentially in this group of women. PATIENTS AND METHODS: Electronic
      patient records and charts of patients who received anthracycline and taxane
      based chemotherapy and subsequently received capecitabine and/or vinorelbine at 3
      Canadian cancer centers, between November 1994 and June 2003, were
      retrospectively reviewed. RESULTS: A total of 140 patients met the study
      eligibility criteria: 45 patients received vinorelbine as a single agent and 68
      received capecitabine as a single agent. The median duration of therapy was 64
      days with vinorelbine and 129 days with capecitabine (P = 0.0012). Median overall
      survival was 102 days for the vinorelbine group and 188 days for the capecitabine
      group (P < 0.0001). Survival at 1 year was 15.6% for the vinorelbine group and
      28.4% for the capecitabine group (P = 0.017). Twenty-seven patients received both
      agents sequentially; and in this group, the median duration of therapy was 110
      days (87 days with vinorelbine and 138 days with capecitabine), and the median
      overall survival was 390 days. CONCLUSIONS: This exploratory analysis suggests
      that patients with tumors previously treated with both anthracycline and taxane
      can still obtain significant survival benefit from further chemotherapy. The
      results indicate that capecitabine may be superior to vinorelbine in this
      setting.

PMID- 17551310
TI  - A phase II study of ABT-510 (thrombospondin-1 analog) for the treatment of
      metastatic melanoma.
AB  - OBJECTIVES: Thrombospondins are natural inhibitors of angiogenesis, tumor
      metastases, and tumor growth (melanoma). ABT-510 is a synthetic analog of
      thrombospondin-1, well tolerated in phase I studies. We conducted a phase II
      trial evaluating the clinical efficacy of ABT-510 and its effects on biomarkers
      of angiogenesis and immunity in patients with metastatic melanoma (MM). PATIENTS
      AND METHODS: A 2-stage phase II clinical trial was conducted to assess the
      clinical efficacy, safety, and pharmacodynamic effects (angiogenesis and
      immunity) of ABT-510 in patients with stage IV melanoma. The primary endpoint was
      18-week treatment failure rate. Patients self-administered 100 mg of ABT-510
      subcutaneously twice daily. Blood samples were collected at baseline and every 3
      weeks while on therapy. Eligible patients demonstrated measurable disease, good
      performance status and no evidence of intracranial metastases. Correlative
      laboratory studies evaluated biomarkers of angiogenesis and immunity. RESULTS:
      Twenty-one patients were enrolled. Most patients were stage M1c (71%) and all had
      prior therapy for MM. Only 3 of the first 20 patients enrolled were progression
      free and on treatment at 18 weeks resulting in early termination of the study.
      Decreases in peripheral blood VEGF-A levels and VEGF-C levels, and CD146 and
      CD34/133 counts relative to pretreatment were detected. Limited changes in
      antitumor T cell immunity were observed. CONCLUSIONS: ABT-510 therapy
      administered at 100 mg twice/day in patients with MM did not demonstrate definite
      clinical efficacy. Further dose escalation or combination with cytotoxic therapy
      may be more effective therapeutically.

PMID- 17551311
TI  - Stereotactic radiosurgical treatment of cerebral metastases arising from breast
      cancer.
AB  - OBJECTIVE: This study was undertaken to evaluate the outcome of patients
      undergoing stereotactic radiosurgery (SRS) as primary or salvage treatment of
      brain metastases arising from breast cancer. MATERIALS AND METHODS: Between July
      2000 and September 2005, the medical records of 49 breast cancer patients who
      underwent SRS for 84 brain metastases were reviewed retrospectively. Thirty-four
      patients received SRS as primary brain metastasis treatment and 15 patients
      received SRS as salvage treatment of brain metastasis recurrence following prior
      whole-brain radiation therapy. The Kaplan-Meier method, univariate comparisons
      with log-rank test, and multivariate analysis were performed. RESULTS: Median
      follow-up was 12 months (range, 5-50 months) and median survival was 19 months
      for all patients. The 1- and 2-year overall survival (OS) rates were 60%, 56%,
      and 55%, 23% for initial SRS alone and SRS salvage groups, respectively (P =
      0.99). A multivariate analysis showed that a high KPS score (KPS > or =90 vs.
      <90; P = 0.02), a higher SIR value (SIR > or =6 vs. <6; P = 0.001),
      postmenopausal status (P = 0.003), and positive estrogen receptor status (P =
      0.04) were predictive of better survival. The 1- and 2-year local control rates
      were 79%, 49%, and 77%, 46% for SRS alone and SRS salvage group, respectively.
      CONCLUSION: SRS can be used as primary treatment of brain metastases or salvage
      of recurrences after whole-brain radiation therapy to achieve good local control
      on the order of close to 80% at 1 year. The median survival of brain metastasis
      patients with breast cancer of 19 months appears favorable compared with the
      general brain metastasis population.

PMID- 17551312
TI  - Early antivascular effects of bevacizumab anti-VEGF monoclonal antibody on
      colorectal carcinomas assessed with functional CT imaging.
AB  - BACKGROUND: The complex effect on anti-VEGF (vascular endothelial growth factor)
      monoclonal antibodies on the tumor vasculature urges studies to identify the
      optimal time frames for the administration of such agents with chemotherapy and
      radiotherapy. PATIENTS AND METHODS: Using CT scan functional imaging, we examined
      the perfusion changes of contrast medium induced 7 days following administration
      of bevacizumab (5 mg/kg iv) in 12 patients with colorectal cancer. RESULTS: CT
      imaging 7 days after the administration of bevacizumab confirmed tumor shrinkage
      in 3 of 12 cases. The mean Haunsfield units after the injection of contrast
      medium were significantly lower 7 days following the administration of
      bevacizumab (P = 0.002). The "perfusion score" significantly decreased after the
      administration of bevacizumab (P = 0.01). In 5 of 12 cases the perfusion score
      was by 45% to 75% decreased, in 3 of 12 minor drop of the perfusion score was
      noted, in 1 of 12 a slight increase was noted, and in 3 of 12 remained unchanged.
      CONCLUSION: It is concluded that the antivascular effects of bevacizumab are
      evident within 7 days from administration in 40% of colorectal carcinomas. The
      mechanisms by which this early antivascular effect may favor the antitumor
      efficacy of radiotherapy and chemotherapy require further investigation.

PMID- 17551313
TI  - Irinotecan with 5-FU/FA in advanced biliary tract adenocarcinomas: a multicenter
      phase II trial.
AB  - OBJECTIVES: Biliary cancer has a poor prognosis and lacks a standard palliative
      chemotherapy. The purpose of this prospective single-arm phase II study was to
      determine the activity and tolerability of irinotecan, 5-fluorouracil, and
      folinic acid in advanced biliary cancer. PATIENTS AND METHODS: Patients with
      inoperable intrahepatic cholangiocarcinoma (ICC) or gallbladder cancer (GBC) and
      no prior chemotherapy were eligible. Irinotecan 80 mg/m2, followed by folinic
      acid 500 mg/m2 and 5-FU 2000 mg/m2 infused over 24 hours (Fufiri) were
      administered weekly 6 times, every 8 weeks. The primary endpoint was response
      rate, and secondary endpoints were overall survival (OS), progression-free
      survival (PFS), and toxicity. RESULTS: Seventeen patients with ICC and 13
      patients with GBC were enrolled. All patients were evaluable for safety. WHO
      grade 3/4 drug-related adverse events occurred in 8 patients (27%), consisting of
      diarrhea and leukopenia in 5 and 3 patients, respectively. One patient with
      diarrhea grade 4 finally succumbed to sepsis. Objective response rate was 10%
      (95% confidence interval, 2.1%-26.5%), with an additional 10% of patients showing
      stable disease. Median overall survival was 166 days and 273 days, and median
      progression-free survival was 84 days and 159 days for ICC and GBC, respectively.
      CONCLUSIONS: Fufiri is a well-tolerated regimen in patients with ICC and GBC but
      has only modest activity in advanced biliary tract cancer.

PMID- 17551314
TI  - The lost connection: the patient-doctor relationship.

PMID- 17551315
TI  - Mesenteric angiosarcoma presenting as a peritoneal carcinomatosis in an 18-month
      old girl.

PMID- 17551316
TI  - Dalteparin-induced skin necrosis in a patient with metastatic lung
      adenocarcinoma.

PMID- 17551317
TI  - Influence of negative affect on selective attention to smoking-related cues and
      urge to smoke in cigarette smokers.
AB  - According to recent models of addiction, negative affect plays an important role
      in maintaining drug dependence. The study investigated the effect of negative
      mood on attentional biases for smoking-related cues and smoking urge in cigarette
      smokers. Eye movements to smoking-related and control pictures, and manual
      response times to probes, were recorded during a visual probe task. Smoking urges
      and mood were assessed by self-report measures. Negative affect was manipulated
      experimentally as a within-participants independent variable; that is, each
      participant received negative and neutral mood induction procedures, in
      counterbalanced order in separate sessions, before the attentional task. There
      were two groups of participants: smokers and nonsmokers. Smokers showed (i) a
      greater tendency to shift gaze initially towards smoking-related cues, and (ii)
      greater urge to smoke when they were in negative mood compared with neutral mood.
      Manual response time data suggested that smokers showed a greater tendency than
      nonsmokers to maintain attention on smoking-related cues, irrespective of mood.
      The results offer partial support for the view that negative mood increases
      selective attention to drug cues, and urge to smoke, in smokers. The findings are
      discussed in relation to an affective processing model of negative reinforcement
      in drug dependence.

PMID- 17551318
TI  - Motivational effects of nicotine as measured in a runway model of drug self
      administration.
AB  - Traditional operant self-administration and conditioned place preference methods
      have yielded inconsistent results in studies of nicotine reinforcement thereby
      hindering efforts to identify the neurobiological systems underlying the drug's
      motivation and reinforcement. This study was designed to assess the motivation of
      subjects to seek nicotine using a runway self-administration procedure. Male
      Sprague-Dawley rats (N=67) were trained to run a straight alley for a single
      daily intravenous injection of nicotine (0.01-0.09 mg/kg/injection) on each of 21
      consecutive trials. Run Speed (1/Run Time) served as the dependent measure for
      the animals' motivation to traverse the alley and enter a goal-box associated
      with intravenous nicotine administration. Nicotine induced an inverted U-shaped
      dose-response curve with the 0.03 mg/kg dose producing optimal runway performance
      over trials. Subjects running for doses larger or smaller than the optimal dose
      exhibited slower running and took longer to enter the goal-box. Thus, the runway
      procedure proved to be an effective methodology for reliably assessing the
      motivation of trained but nondrugged animals to seek intravenous nicotine.

PMID- 17551319
TI  - Comparison of the mGluR1 antagonist A-841720 in rat models of pain and cognition.
AB  - In the current study we compared the potency of the selective metabotropic
      glutamate receptor (mGluR1) antagonist A-841720 (7-Azepan-1-yl-4-dimethylamino-7H
      9-thia-1,5,7-triaza-fluoren-8-one) in rodent models of pain with its effects in
      models of learning and memory, to obtain information regarding the therapeutic
      window of this compound. A-841720 significantly reduced formalin-induced
      behaviours and complete Freund's adjuvant (CFA)-induced tactile allodynia,
      starting at doses of 1 and 10 mg/kg, respectively. At the dose of 3 mg/kg,
      however, A-841720 significantly reduced the percentage of spontaneous
      alternations in a radial-maze task. In contextual-fear conditioning, A-841720,
      given at the dose of 10 mg/kg before acquisition, significantly reduced freezing
      behaviour tested 24 h later. In the same task, repeated treatment for 5 days did
      not reduce the impairing effect of the challenge dose, indicating a lack of
      tolerance development. In a passive-avoidance task, A-841720 at 10 mg/kg
      administered before acquisition, significantly reduced the latency to enter the
      dark box on the retention test. Given that complete Freund's adjuvant is a better
      measure of analgesia, these results indicate that the selective mGluR1 antagonist
      A-841720 has analgesic potential in a dose range at which it also produces memory
      impairments. This diminishes its therapeutic potential for the treatment of
      chronic pain.

PMID- 17551320
TI  - Behavioral effects of dipropyltryptamine in rats: evidence for 5-HT1A and 5-HT2A
      agonist activity.
AB  - These studies investigated the role of serotonin-1A (5-HT1A) and 5-HT2A receptors
      in the behavioral effects of dipropyltryptamine (DPT). Eight rats discriminated
      0.56 mg/kg 2,5-dimethoxy-4-methylamphetamine (DOM) from saline and responded
      under a fixed ratio 5 schedule of food presentation; 12 other rats were used for
      observational studies. DOM and DPT increased responding on the DOM lever with 3.2
      mg/kg DPT producing greater than 95% responding on the DOM lever; this effect of
      DPT was antagonized by the 5-HT2A receptor antagonist MDL100907. In another
      study, the 5-HT1A and 5-HT7 receptor agonist 8-OH-DPAT produced lower-lip
      retraction and, at larger doses, flat body posture; DPT alone produced flat body
      posture and not lower-lip retraction; MDL100907 alone did not produce either
      effect. Pretreatment with DPT blocked 8-OH-DPAT-elicited lower-lip retraction,
      suggesting antagonist activity of DPT at 5-HT1A receptors; however, in the
      presence of MDL100907 DPT produced not only flat body posture but also lower-lip
      retraction, suggesting that agonist activity of DPT at 5-HT2A receptors masked
      agonist activity at 5-HT1A receptors. Lower-lip retraction and flat body posture
      by DPT in the presence of MDL100907 were attenuated by the 5-HT1A receptor
      antagonist WAY100635. These findings suggest that DPT has agonist activity at 5
      HT1A and 5-HT2A receptors and that effects at 5-HT2A receptors mask effects at 5
      HT1A receptors.

PMID- 17551321
TI  - Nitric oxide modulates state dependency induced by lithium in an inhibitory
      avoidance task in mice.
AB  - The effect of intracerebroventricular (i.c.v.) injections of L-arginine, a nitric
      oxide (NO) precursor and L-NAME, an inhibitor of NO synthase, on retrieval of
      state-dependent memory induced by LiCl (lithium) was investigated. A one-trial
      step-down inhibitory avoidance task was used for memory assessment in adult male
      NMRI mice. Intraperitoneal administration of lithium (10 mg/kg), immediately
      after training, impaired memory on the test day. Pretest administration of
      different doses of lithium (5, 10 and 20 mg/kg) reversed the impairment of memory
      caused by posttraining lithium (10 mg/kg). In addition, pretest administration of
      L-arginine (0.001, 0.01 and 0.1 microg/mouse, i.c.v.) or L-NAME (0.001, 0.01 and
      0.1 microg/mouse, i.c.v.) also reversed amnesia induced by posttraining lithium.
      Furthermore, pretest coadministration with lithium of a dose of L-arginine
      (0.0001 microg/mouse, i.c.v.) or L-NAME (0.0001 microg/mouse, i.c.v.) that had no
      effects when administered alone, increased the effect of lithium on retrieval of
      inhibitory avoidance memory. The results suggest that NO may have a modulatory
      role on state-dependent retrieval of inhibitory avoidance memory induced by
      lithium.

PMID- 17551322
TI  - Quantifying the psychomotor activating effects of cocaine in the rat.
AB  - Studies that involve analysis of the psychomotor activating effects of drugs
      often use locomotor activity as the sole measure of psychomotor activation. At
      low doses, psychostimulant drugs typically produce primarily locomotor
      hyperactivity. As dose is increased, behavior, however, changes in complex ways,
      in part because of a transition to behavior progressively dominated by more and
      more stereotyped actions, such as repetitive head movements. Thus, at some doses
      an increase in a drug effect is reflected by an increase in locomotion and at
      others by a decrease, making the interpretation of changes in locomotor activity
      difficult. Using an automated video analysis system (Clever Sys., Inc. Reston,
      Virginia, USA), we quantified various components of the psychomotor response to
      cocaine in the rat, including locomotor activity and lateral head movements, as
      well as the velocity and/or frequency of these behaviors. We report that the
      combination of these measures provides an especially sensitive measure of the
      psychomotor activating effects of cocaine, and how behavior changes as a
      consequence of repeated drug treatment.

PMID- 17551323
TI  - Morphine-induced sensitization in mice: changes in locomotor activity by prior
      scheduled exposure to GABAA receptor agents.
AB  - This study investigated the effects of a gamma-amino-butyric acid type A (GABAA)
      receptor agonist and antagonist on morphine-induced locomotor sensitization in
      male albino mice. Subcutaneous administration to mice of a high dose of morphine
      (30 mg/kg), but not lower doses (5, 10 and 20 mg/kg) increased locomotion. The
      maximum locomotor activity was achieved during a 20-min measurement period. The
      locomotor response to a low dose of morphine (5 mg/kg, subcutaneously) given on
      day 9 was enhanced in mice pretreated with morphine (7.5, 15 and 30 mg/kg/day x 3
      days), indicating that sensitization had developed. Three-day
      intracerebroventricular (i.c.v.) administration of the GABAA receptor agonist,
      muscimol (0.025, 0.05, 0.1 and 0.2 microg/mouse/day) significantly decreased both
      morphine-induced motor stimulation and locomotor sensitization. On the other
      hand, a 3-day pretreatment with the GABAA-receptor antagonist, bicuculline (0.25,
      0.5 and 1 microg/mouse/day) reduced morphine (15 mg/kg)-induced locomotor
      sensitization. Repeated i.c.v. injections of a lower dose of bicuculline (0.25
      microg/mouse/day x 3 days) by itself also decreased morphine-induced locomotion.
      Furthermore, repeated i.c.v. administration of bicuculline (0.25, 0.5 and 1
      microg/mouse/day x 3 days) decreased the effect of i.c.v. injection of muscimol
      (0.1 microg/mouse/day x 3 days) on locomotor activity induced by morphine (5
      mg/kg) in both control and sensitized mice. The magnitude of this response was,
      however, variable. The results indicate that GABAA receptors might be involved in
      the acquisition of morphine-induced sensitization.

PMID- 17551324
TI  - Lack of evidence for appetitive effects of Delta 9-tetrahydrocannabinol in the
      intracranial self-stimulation and conditioned place preference procedures in
      rodents.
AB  - Data on the ability of Delta 9-tetrahydrocannabinol (THC) to modify reward
      processes in experimental animals are inconsistent. This study examined the
      effects of Delta 9-THC on brain reward function using the rate-frequency curve
      shift paradigm of intracranial self-stimulation (ICSS) and the conditioned place
      preference (CPP) paradigm. In ICSS tests, rats were implanted with electrodes
      into the medial forebrain bundle. After brain stimulation reward thresholds
      stabilized, rats received intraperitoneal injections of Delta 9-THC (0, 0.5, 1
      and 2 mg/kg) or the CB1 receptor antagonist SR141716A (0, 0.02 mg/kg) and Delta 9
      THC (0, 2 mg/kg). The two highest doses of Delta 9-THC significantly increased
      the threshold ICSS frequency. SR141716A reversed the action of Delta 9-THC (2
      mg/kg), without affecting reward thresholds by itself. In the CPP test, mice
      received intraperitoneal injections of Delta 9-THC (0, 1 or 3 mg/kg). Delta 9-THC
      showed neither statistically significant preference nor aversion in either of the
      doses tested. These findings indicate that Delta 9-THC, in contrast to other
      drugs of abuse, does not facilitate ICSS or support CPP under the present
      experimental conditions, but rather has a dose-dependent inhibitory influence on
      ICSS.

PMID- 17551325
TI  - Further delineation of interstitial chromosome 6 deletion syndrome and review of
      the literature.
AB  - Interstitial deletions of chromosome 6q are a relatively rare finding. Deletions
      have ranged from the loss of a single band to larger deletions spanning multiple
      bands. The clinical phenotype varies, but some features commonly seen include
      cardiac anomalies, hypotonia, facial dysmorphism and mental retardation. To
      further delineate the syndrome, we report an infant with facial dysmorphism,
      ectrodactyly and tetralogy of Fallot owing to interstitial deletion 6q16.1
      6q22.32. On array comparative genomic hybridization analysis, the deletion
      spanned from the 93 377 323rd base to the 127 650 582nd base on chromosome 6
      [coordinates are based on Human Mar. 2006 (hg18) assembly of International Human
      Genome Sequencing Consortium]. A literature review identified 16 additional cases
      with overlapping interstitial deletions of chromosome 6q between q13 and q23.1.
      Genotype-phenotype correlations are considered.

PMID- 17551326
TI  - Adams-Oliver syndrome: further evidence of an autosomal recessive variant.
AB  - Adams-Oliver syndrome is characterized by aplasia cutis congenita and variable
      degrees of terminal transverse limb defects. Other associated anomalies were
      described in the syndrome. Most described cases follow an autosomal dominant
      pattern of inheritance. Sporadic and autosomal recessive cases, however, were
      reported. In this study, we report on three Egyptian patients with Adams-Oliver
      syndrome from three different families. The parents were normal and
      consanguineous in all three families. There was history of similarly affected
      sibs for two cases. These findings denote autosomal recessive inheritance. The
      reported cases had typical skull and limb anomalies with cutis marmorata
      telangiectatica congenita. We observed additional rare manifestations in the form
      of microcephaly, psychomotor retardation, epilepsy, eye anomalies and atrophic
      skin lesions. MRI of the brain in one of the studied cases revealed
      retrocerebellar cyst and mild asymmetrical cerebellar hypoplasia, which to our
      knowledge, were not previously reported in Adams-Oliver syndrome. The results of
      this study provide further evidence of clinical and genetic heterogeneity and
      support the presence of autosomal recessive variant of Adams-Oliver syndrome.

PMID- 17551327
TI  - Unusual facies, thumb hypoplasia, distinctive spinal fusions and extraspinal
      mobility limitation, in a pair of monozygotic twins.
AB  - We report a pair of monozygotic twins with unusual facies and hypoplastic thumbs
      associated with progressive spinal fusion and joint immobility. The radiographic
      features were neither consistent with the multiple synostosis syndrome of
      Herrmann, nor with the spondylocarpotarsal synostosis syndrome. The overall
      spinal radiographic abnormalities seen in our patients were suggestive of an
      exceptionally early onset of Forestier disease (anterolateral, perivertebral,
      ligament ossification), but the thumb hypoplasia and pterygium colli are not seen
      in that condition. We report what might be a novel genetic entity.

PMID- 17551328
TI  - A case of multiple vertebral segmentation defects, unilateral renal agenesis, and
      an unusual 'Cooley-like' hand appearance.
AB  - We report an apparently healthy 5-year-old girl with multiple vertebral
      segmentation defects, partial fusion of some left ribs, abnormal vertebral
      arches, left renal agenesis, and a 'Cooley-like' hand appearance radiologically.
      The costovertebral defects were extensive but not contiguous, which establishes
      this case as being different from the Mendelian forms of spondylocostal
      dysostosis. The extended skeletal involvement raises the question as to how this
      case is classified within this heterogeneous group of disorders and we believe
      this might represent a new and distinct entity.

PMID- 17551329
TI  - Hydrocephalus and moderate mental retardation in a boy with Van der Woude
      phenotype and IRF6 gene mutation.
AB  - In this report, we present a boy with lower lip pits, distinct craniofacial
      dysmorphism with cleft lip and palate, central nervous system malformation, and
      severe mental retardation. Similar but less pronounced facial findings were
      present in his mentally normal mother and maternal grandfather, both presenting
      with lower lip pits. Cleft lip was present in patient's father. Analysis of the
      VWS1 and VWS2 regions were performed to elucidate the molecular basis of the
      phenotype of the propositus. Screening for mutations at the IRF6 gene detected a
      pathogenic mutation (c.960G>C) in the propositus and in his mother; and a single
      nucleotide polymorphism (c.175-5C>G) in the propositus and in his father.
      Clinical and genetic aspects of this case are discussed.

PMID- 17551330
TI  - Parkes Weber syndrome occurring in a family with capillary malformations.
AB  - Parkes Weber syndrome is a disorder characterized by cutaneous blush,
      arteriovenous fistula, and overgrowth of the affected limb. It has been
      differentiated from Klippel-Trenaunay syndrome on the basis of the presence of
      arteriovenous fistula that are always absent in the latter. We report a case of
      Parkes Weber syndrome with diffuse arteriovenous high flow leading to hemodynamic
      complications but without radiographic evidence of arteriovenous fistula. There
      are multiple individuals in the family with capillary malformations inherited in
      an autosomal dominant pattern. These observations reinforce the suggestions that
      Parkes Weber syndrome and capillary malformations may share a common pathogenetic
      pathway.

PMID- 17551331
TI  - A novel mutation in TRIM37 is associated with mulibrey nanism in a Turkish boy.
AB  - Mulibrey nanism is a rare autosomal-recessive disorder characterized by prenatal
      onset severe growth retardation and pericardial constriction associated with
      abnormalities of muscle, liver, brain and eye. More than 80% of previously
      reported patients are of Finnish origin in whom a founder mutation in the TRIM37
      gene have been described. We report on a 7-year-old Turkish boy who presented
      with classical phenotypic features of mulibrey nanism. Mutation screening of the
      TRIM37 gene revealed that the proband had a homozygous two base pair deletion,
      c.1894_1895delGA, resulting in a frame-shift and a premature termination codon.
      Our proband is one of the rare examples of mulibrey nanism outside Finland and
      extends the mutation spectrum in this disorder.

PMID- 17551332
TI  - Antenatal diagnosis of deletion chromosome 11(q23-qter) (Jacobsen syndrome).
AB  - A case of Jacobsen syndrome, suspected antenatally on the grounds of
      trigonocephaly and hypoplastic left heart syndrome, is presented. Clinicians are
      reminded that a hypoplastic left heart should not be assumed to be an isolated
      malformation and that a careful search for associated malformations can
      facilitate the recognition of an underlying genetic syndrome.

PMID- 17551333
TI  - Velocardiofacial syndrome with a rare t(2;22).
AB  - Rearrangements involving chromosomes 2 and 22 were described not only as acquired
      abnormalities in a variety of human neoplasias but also in the constitutional
      karyotype suggesting the existence of a greater fragility in some specific
      regions in these chromosomes. Patients with DiGeorge and Velocardiofacial
      syndromes have a deletion on 22q11 leading to haploinsufficiency for one or more
      gene(s). We report a patient with velocardiofacial syndrome in which cytogenetic
      and fluorescence in situ hybridization analysis showed a rare t(2;22) and
      deletion in the 22q11 region.

PMID- 17551334
TI  - A new case of VACTERL association with unilateral amelia of upper limb.

PMID- 17551335
TI  - Osteogenesis imperfecta and holoprosencephaly.
AB  - A 17-week female fetus had severe osteogenesis imperfecta and gross
      holoprosencephaly. This unusual combination has not previously been documented.
      No obvious environmental or genetic determinants were present.

PMID- 17551336
TI  - Preaxial polydactyly in neurofibromatosis 1.
AB  - Although skeletal manifestations are a cardinal feature of neurofibromatosis 1,
      they are largely confined to the axial skeleton and tibiae. In contrast,
      congenital malformations of the extremities are less common in patients with
      neurofibromatosis 1, occurring in fewer than 10%. We describe a boy with
      bilateral, symmetrical polysyndactyly (preaxial polydactyly type IV) and
      neurofibromatosis 1. This report discusses peripheral skeletal malformations in
      neurofibromatosis 1 and their possible etiology.

PMID- 17551337
TI  - Unilateral partial absence of the fallopian tube in Williams syndrome: a new
      feature?

PMID- 17551338
TI  - Cranio-osteoarthropathy in sibs.
AB  - Primary hypertrophic osteoarthropathy is a condition characterized by clubbing,
      arthropathy and periostosis of long tubular bones. Three variants of primary
      hypertrophic osteoarthropathy are distinguished: pachydermoperiostosis, which
      shows as additional symptom pachydermia; cranio-osteoarthropathy, which has a
      decreased neurocranium ossification as additional feature; and a secondary form.
      Primary hypertrophic osteoarthropathy is also genetically heterogeneous, with
      evidence for both autosomal dominant and autosomal recessive inheritance. We
      describe two sibs with cranio-osteoarthropathy and briefly review previously
      reported cases. The present cases demonstrate the phenotypic variability of the
      condition. The consanguinity in the present family and analysis of previously
      described cases support autosomal recessive inheritance for cranio
      osteoarthropathy.

PMID- 17551339
TI  - Congenital ulcerating hemangioma in a baby with KRAS mutation and cardio-facio
      cutaneous syndrome.
AB  - CFC syndrome is a genetically heterogenous condition. Missense mutations have
      been identified in BRAF, KRAS, MEK1 and MEK2. We have reported here a KRAS
      mutation in a baby girl with an early clinical diagnosis of CFC syndrome
      associated with a large ulcerating hemangioma. Although ectodermal abnormalities
      have been described in all individuals with this condition, features such as
      ichthyosis and hemangioma have been previously found only in those patients
      carrying a mutation in BRAF, and not in KRAS. The findings we have described
      contrast with these observations. The relatively high frequency of hemangiomas in
      CFC syndrome suggests that defects in the expression of the MAPK pathway may
      alter endothelial cell proliferation. Increased understanding of how the
      molecular pathways with which defects in CFC syndrome predispose affected
      individuals to hemangiomas might offer insights into the pathogenesis of this
      common childhood tumour in the general population.

PMID- 17551340
TI  - Kallmann syndrome presenting as congenital ptosis in brothers.

PMID- 17551341
TI  - Seckel syndrome with Morgagni hernia.
AB  - Seckel syndrome is an autosomal recessive disease presenting with microcephalic
      dwarfism, mental retardation and facial and skeletal abnormalities. Morgagni
      hernia is quite rare, constituting 1-6% of all diaphragmatic hernias. It is
      asymptomatic, especially in childhood. Morgagni hernia has never been reported in
      patients with Seckel Syndrome. Here we report a 3-year-old boy diagnosed as
      having Seckel Syndrome with Morgagni hernia, which has to be considered during
      physical examination of patients.

PMID- 17551343
TI  - Does the treatment of mental disorders in childhood lead to a healthier
      adulthood?
AB  - PURPOSE OF REVIEW: To review mechanisms by which intervention for childhood
      mental disorders may exert an influence on mental health and wellbeing in
      adulthood, the challenges to demonstrating long-term benefit or harm from such
      intervention, existing evidence of long-term benefit, and strategies for
      improving the long-term benefit of treatment. RECENT FINDINGS: Intervention may
      improve long-term outcome through the promotion of protective interpersonal
      relationships, by enhancing scholastic and later occupational functioning, by
      arresting the progression of disorder, and by improving general health.
      Challenges to demonstrating benefits or harms in the long term include
      variability in the natural course of childhood mental disorders, heterotypic
      outcomes, and the influence of other variables over time on long-term
      functioning. Examples of demonstrated benefit include the lowering of risk for
      substance abuse seen with psychostimulant treatment for attention
      deficit/hyperactivity disorder, improved outcomes for autism since the
      introduction of early interventions to address language impairment, and reduced
      mortality in anorexia nervosa. SUMMARY: There are feasible enduring benefits of
      treatment for childhood mental disorders. Treatment of complex problems may have
      a greater long-term impact than in conditions that follow a benign natural
      course. Success requires more assertive approaches to treatment than are
      traditionally employed by child and adolescent mental health services.

PMID- 17551344
TI  - Service responses for youth onset mental disorders.
AB  - PURPOSE OF REVIEW: Many psychiatric disorders have their highest first-onset
      rates in adolescence and young adulthood. We summarize recent work indicating
      where interventions are most needed and effective. We also review the literature
      that examines the scope for reorienting mental health services to meet the needs
      of adolescents and young adults. RECENT FINDINGS: The continuities between youth
      onset and later life disorders, as well as later social adjustment, have become
      clearer. Emotional disorders that persist or recur during the teens have the
      greatest effect on future mental health. To date, service systems, even in the
      developed world, cater poorly for youth with mental disorders. Intervention
      studies demonstrate the short-term benefits of intensive multidisciplinary
      intervention for early psychosis. There are few data concerning the benefit of
      early intervention for other disorders. Long-term benefits for early intervention
      for any condition are unknown. Youth streams of psychiatric care have developed
      for early-onset psychotic disorders. SUMMARY: An increasing understanding of the
      high prevalence and longer-term effects of youth onset mental disorders has not
      yet been adequately matched by intervention research or the evaluation of
      different models of mental health service delivery.

PMID- 17551345
TI  - Prevention and early intervention for depression in young people--a practical
      possibility?
AB  - PURPOSE OF REVIEW: Many studies aimed at prevention and early intervention for
      mental disorders have focused on depressive disorder because it causes
      substantial disability. In this review, recent developments in prevention and
      early intervention with children and adolescents who are depressed are
      summarized. RECENT FINDINGS: Despite early promise, there is little evidence that
      prevention of depression is a practical possibility at this stage. There is no
      clear evidence of effectiveness for universal programmes. Targeted programmes are
      more promising, with evidence of short-term reduction in depressive symptoms, and
      there are a few studies in which there is evidence of a reduced incidence of
      disorder. There are promising developments in efforts to screen for disorder,
      although there is a requirement for more effective therapy. Potential cost
      savings are considerable, so it is imperative that the search continues for
      effective interventions for depression in young people. Attention to wider social
      issues that impact on mental health is also needed. SUMMARY: Developing
      preventive services for depression is premature at this stage. There is evidence
      to support screening for depression and providing early intervention, but current
      treatments have limited effectiveness. There is a compelling need for further
      research in this area.

PMID- 17551346
TI  - Care pathways for young people who misuse substances: using the evidence to
      design services.
AB  - PURPOSE OF REVIEW: To review a selection of the literature on the nature and
      contents of care pathways. We examine recent work on current trends in
      intervening to meet the needs of young people who misuse substances. RECENT
      FINDINGS: The recent and growing literature encourages us to adopt care pathways
      as structured models for service delivery. The increased prevalence and the
      severity and complexity of the problems experienced by young people who misuse
      substances evidence the requirement for specialist services for them. SUMMARY:
      The literature argues for using care pathways to manage better services for
      intervening with young people who use or misuse substances and recommends their
      contents. We conclude that care pathways should be based on strategic models of
      care; however, there remain areas of uncertainty, including those about the
      balance of services that should be delivered, adoption of prevention programmes,
      and development of audit tools to monitor the impacts and effectiveness of care
      pathways. This review provides our recommended list of contents for models of
      care on which we recommend that associated care pathways should be based.

PMID- 17551347
TI  - Deliberate self-harm in adolescents.
AB  - PURPOSE OF REVIEW: To review literature on young people who deliberately harmed
      themselves that was published between March 2005 and December 2006 in English
      language journals. RECENT FINDINGS: Recent follow-up studies have confirmed that
      deliberate self-harm at a young age is an important indication of mental health
      problems in later life, including a strongly increased risk of subsequent
      suicidal behavior. Main recent research includes study of risk factors and
      predictors of deliberate self-harm, and continuing study of the effects of
      pharmacological treatment, in particular selective serotonin reuptake inhibitors,
      in children and adolescents. SUMMARY: Recent findings regarding risk factors of
      adolescent deliberate self-harm confirm the importance of depressive disorders,
      deficient problem solving, exposure to suicidal behavior and familial
      characteristics. More biological studies of young people are required to provide
      evidence regarding neurobiological correlates of risk factors of suicidality in
      young people. The association between the use of antidepressants in depressed
      children and adolescents and the emergence of suicidal behavior continues to be a
      matter of debate due to the conflicting evidence from ecological or observational
      studies and meta-analyses. Although psychotherapeutic approaches have been
      examined less extensively, the results regarding cognitive behavior therapy in
      depressed and suicidal young people are clearly positive. Measures to prevent
      suicidal behavior in young people require further research.

PMID- 17551348
TI  - Recent advances in the theories of and interventions with attachment disorders.
AB  - PURPOSE OF REVIEW: The present review examines the available literature to
      consider recent advances in the theories of, and interventions with, disorders of
      attachment. We discuss the existing evidence to argue that the conceptualization
      of attachment disorders remains problematic despite their clinical significance.
      RECENT FINDINGS: Research into clinical disorders of attachment is limited, but
      there is some recent evidence that a standardized approach to diagnosis may
      improve identification. The current classificatory systems do not accommodate all
      clinical presentations and proposed broader approaches have greater clinical
      utility. A recent review of interventions for attachment disordered children
      confirms that 'coercive' interventions have no empirical support and are not
      biased on coherent principles of attachment theory. SUMMARY: Clinical interest in
      identification and treatment of attachment disorders has remained high. This is
      despite continuing confusion regarding terminology, phenomenology and diagnosis.
      The lack of agreed definition and conceptualization of these conditions is
      reflected in disparate approaches to intervention and limited empirical data.
      Interventions have little demonstrated benefit and some potential risk.

PMID- 17551349
TI  - Critical review of world policies for mental healthcare for children and
      adolescents.
AB  - PURPOSE OF REVIEW: Policy development is essential for the development of child
      and adolescent mental health services. The gaps in policy and knowledge on how to
      develop policy have hindered the development of sustainable services. RECENT
      FINDINGS: The WHO has now objectively identified gaps in child and adolescent
      mental health policy and services worldwide through its Atlas project. Others
      have identified the need to use evidence-based interventions in developing
      services and the need for ongoing evaluation. These latter elements are essential
      for effective policy implementation. SUMMARY: Data are now available worldwide to
      move forward with advocacy for child and adolescent mental health policy
      development.

PMID- 17551350
TI  - Magnitude and impact of comorbidity of mental disorders from epidemiologic
      surveys.
AB  - PURPOSE OF REVIEW: To consider comorbidity across multiple classes of disorders
      in data derived from recent large-scale community surveys. RECENT FINDINGS: There
      has been substantial recent progress in our understanding of patterns and
      implications of comorbidity of mental disorders. There is now converging evidence
      on the magnitude and specific patterns of comorbidity in international studies
      worldwide. There is increasing recognition of comorbidity of mental and physical
      disorders. Comorbidity of mental disorders and substance abuse has now been
      recognized universally, and the results of treatment and prevention studies
      incorporating comorbidity are now beginning to emerge. SUMMARY: Comorbidity has
      been shown to be an index of more severe course and outcome of mental disorders.
      Systematic inclusion of comorbidity into clinical evaluation and treatment will
      enhance the effectiveness of intervention with these conditions. Prevention of
      the development of secondary conditions as a consequence of primary disorders
      should reduce the impact of these conditions on both the individual and society.

PMID- 17551351
TI  - Age of onset of mental disorders: a review of recent literature.
AB  - PURPOSE OF REVIEW: The aim of this article is to review recent epidemiological
      research on age-of-onset of mental disorders, focusing on the WHO World Mental
      Health surveys. RECENT FINDINGS: Median and inter-quartile range (IQR; 25th-75th
      percentiles) of age-of-onset is much earlier for phobias (7-14, IQR 4-20) and
      impulse-control disorders (7-15; IQR 4-35) than other anxiety disorders (25-53,
      IQR 15-75), mood disorders (25-45, IQR 17-65), and substance disorders (18-29,
      IQR 16-43). Although less data exist for nonaffective psychosis, available
      evidence suggests that median age-of-onset is in the range late teens through
      early 20s. Roughly half of all lifetime mental disorders in most studies start by
      the mid-teens and three quarters by the mid-20s. Later onsets are mostly
      secondary conditions. Severe disorders are typically preceded by less severe
      disorders that are seldom brought to clinical attention. SUMMARY: First onset of
      mental disorders usually occur in childhood or adolescence, although treatment
      typically does not occur until a number of years later. Although interventions
      with early incipient disorders might help reduce severity-persistence of primary
      disorders and prevent secondary disorders, additional research is needed on
      appropriate treatments for early incipient cases and on long-term evaluation of
      the effects of early intervention on secondary prevention.

PMID- 17551352
TI  - Schizoaffective disorder merges schizophrenia and bipolar disorders as one
      disease--there is no schizoaffective disorder.
AB  - PURPOSE OF REVIEW: Schizoaffective disorder was named as a compromise diagnosis
      in 1933, and remains popular as judged by its place in the International
      Classification of Diseases and the Diagnostic and Statistical Manual of Mental
      Disorders, its frequent use in clinical practice, and its extensive discussion in
      the literature. Some, however, have questioned the validity of schizoaffective
      disorder as separate from psychotic mood disorder. We examined the literature to
      assess the rationale for the continuation of schizoaffective disorder as a
      legitimate diagnostic category. RECENT FINDINGS: The diagnosis of schizoaffective
      disorder depends on the disease specificity of the diagnostic criteria for
      schizophrenia; however, the psychotic symptoms for schizophrenia, traditionally
      held as specific, can be accounted for by psychotic bipolar. Further, the
      interrater reliability for diagnosing schizoaffective disorder is very low. A
      recent and expanding body of comparative evidence from a wide range of clinical
      and basic science studies, especially genetic, reveals multiple similarities
      between schizoaffective disorder, schizophrenia and psychotic bipolar. SUMMARY:
      Schizoaffective disorder unifies schizophrenia and bipolar, blurring the zones of
      rarity between them and suggesting that schizoaffective disorder is not a
      separate, 'bona-fide' disease. Patients diagnosed with schizoaffective disorder
      likely suffer from a psychotic mood disorder. The diagnosis of schizoaffective
      disorder, which can result in substandard treatment, should be eliminated from
      the diagnostic nomenclature.

PMID- 17551353
TI  - The epidemiology of the dementias: an update.
AB  - PURPOSE OF REVIEW: The epidemiology of dementia is one of the priority fields in
      aging research. This review aims to highlight the most relevant findings over
      last years concerning occurrence, risk factors, and prevention of dementia and
      its major subtypes. RECENT FINDINGS: It is estimated that currently around 24
      million people have dementia in the world, with the number being projected to
      double every 20 years, and that 60% of dementia patients live in developing
      countries, with the proportion being raised to more than 70% by 2040. Current
      evidence suggests that vascular factors, such as midlife hypertension, diabetes,
      and cerebrovascular disease, contribute significantly to the development of
      dementia and Alzheimer's disease, and that active engagement in mental, physical,
      and social activities may postpone the onset of dementia by providing cognitive
      reserve. SUMMARY: Dementia represents a major public health challenge as a
      consequence of rapid increase in the aging population worldwide, especially in
      developing countries. This challenge can be partly confronted by successful
      development of preventive strategies. Evidence has emerged that proper control of
      vascular disorders and maintenance of active lifestyles may prevent or delay the
      onset and progression of dementia and Alzheimer's disease. Intervention trials
      are warranted to determine, to what extent, such programs are effective against
      dementia.

PMID- 17551354
TI  - Epidemiology of attention-deficit/hyperactivity disorder across the lifespan.
AB  - PURPOSE OF REVIEW: Prevalence estimates of the attention-deficit hyperactivity
      disorder (ADHD) and the rate of persistence of symptoms across the lifespan are
      heterogeneous, raising questions about the validity of the diagnosis. This review
      aims to discuss potential reasons for variability in ADHD prevalence estimates
      and rates of symptom persistence, as well as to present ADHD prevalence rates
      during the lifespan. RECENT FINDINGS: The best available estimates of ADHD
      prevalence are around 5.29% for children and adolescents and 4.4% in adulthood.
      Estimates of ADHD prevalence and rate of symptom persistence over time seem to be
      highly affected by methodological characteristics of the studies. SUMMARY: The
      review of ADHD epidemiology highlights the need for standardizing study
      methodologies to make findings comparable. Even so, epidemiological cross
      national data seem to support the validity of ADHD.

PMID- 17551355
TI  - Prevalence and correlates of cannabis use in developed and developing countries.
AB  - PURPOSE OF REVIEW: The aim of this article is to review recent research on the
      prevalence, antecedents and correlates of cannabis use in young adults in
      developed and developing countries. RECENT FINDINGS: Cannabis is the most widely
      used illicit drug globally and its use appears to be increasing in developed and
      developing countries. In developed countries rebelliousness, antisocial
      behaviour, poor school performance, and affiliation with drug-using peers are
      risk factors for early and regular cannabis use. Similar antecedents are now
      being reported in developing countries. Dependence is an underappreciated risk of
      cannabis that affects one in six to seven adolescents who use cannabis in
      developed countries. Adolescent cannabis dependence is correlated with an
      increased risk of using other illicit drugs, symptoms of depression, and symptoms
      of psychosis. The plausibility of cannabis playing a contributory causal role has
      increased for symptoms of psychosis in longitudinal studies but remains
      contentious. In the case of other illicit drug use and mood disorders common
      causal explanations remain difficult to exclude. SUMMARY: Early and regular
      cannabis use in adolescence predicts an increased risk of cannabis dependence
      which in turn predicts an increased risk of using other illicit drugs, and
      reporting symptoms of mood and psychotic disorders.

PMID- 17551356
TI  - Concurrent medical conditions with pediatric bipolar disorder.
AB  - PURPOSE OF REVIEW: Pediatric bipolar disorder is a serious mental illness with
      significant morbidity and mortality. A variety of medical and psychiatric
      conditions occur concurrently with bipolar disorder. These conditions have been
      more frequently reported in adults. There prevalence in pediatric bipolar
      disorder is less known. This report is particularly relevant and timely due to
      the chronic nature of bipolar disorder and the profound impact on health that its
      treatments can bring. This evolving area needs to be understood to maximize
      clinical outcomes. RECENT FINDINGS: While little has been published about
      pediatric bipolar disorder and its concurrent medical conditions specifically,
      many reports that focused on adults included pediatric subjects. Concurrent
      medical conditions fall into a small number of groupings. (1) Those that are
      related to bipolar disorder or its treatment. (2) Medical conditions that mimic
      mania. (3) Conditions that occur more commonly in patients with bipolar disorder,
      but do not appear to be related to its treatment. (4) Those that may be related
      to risk behaviors associated with bipolar disorder. SUMMARY: Many medical
      conditions that occur concurrently with bipolar disorder in adults are also
      present in youth. The premature (iatrogenic) initiation of some conditions
      related to its treatment may pose specific ethical dilemmas for those treating
      psychiatric conditions.

PMID- 17551357
TI  - Medical problems in schizophrenia patients living in the community (alternative
      facilities).
AB  - PURPOSE OF REVIEW: In recent years, interest in physical illnesses among patients
      with schizophrenia has increased. A great majority of schizophrenia patients live
      in the community and in alternative facilities. This review aims to report
      studies on medical problems in patients living in the community. RECENT FINDINGS:
      Few relevant studies could be found. During the deinstitutionalization process,
      medical comorbidity seems to be increased in patients living in the community and
      in alternative facilities. According to the reviewed studies, in which men have
      been overrepresented, a great majority of patients with schizophrenia living in
      the community suffer from physical illnesses and functional restrictions caused
      by them. Of individual medical problems, obesity, diabetes, cardiovascular and
      lung diseases are the most prevalent. In many cases, however, medical problems in
      schizophrenia patients have remained undetected. SUMMARY: Medical problems are
      prevalent in patients with schizophrenia living in the community and in
      alternative facilities, and they require greater attention from both psychiatric
      and medial health personnel. Preventive measures for improving the patient's
      health behaviour and paying attention to metabolic adverse effects of neuroleptis
      are needed, as are more studies.

PMID- 17551359
TI  - Bibliography. Current world literature. Child and adolescent psychiatry.

PMID- 17551358
TI  - Medical comorbidity in bipolar disorder: re-prioritizing unmet needs.
AB  - PURPOSE OF REVIEW: The aim of this review is to synthesize results from extant
      investigations which report on the co-occurrence of bipolar disorder and medical
      comorbidity. RECENT FINDINGS: We conducted a MEDLINE search of all English
      language articles published between January 2004 and November 2006. Most studies
      report on medical comorbidity in bipolar samples; relatively fewer studies report
      the reciprocal association. Individuals with bipolar disorder are differentially
      affected by several 'stress-sensitive' medical disorders notably circulatory
      disorders, obesity and diabetes mellitus. Neurological disorders (e.g. migraine),
      respiratory disorders and infectious diseases are also prevalent. Although
      relatively few studies have scrutinized the co-occurrence of bipolar disorder in
      medical settings, individuals with epilepsy, multiple sclerosis, migraine and
      circulatory disorders may have a higher prevalence of bipolar disorder. A
      clustering of traditional and emerging (e.g. immuno-inflammatory activation) risk
      factors presage somatic health issues in the bipolar disorder population.
      Iatrogenic factors and insufficient access to primary, preventive and integrated
      healthcare systems are also contributory. SUMMARY: Somatic health issues in
      individuals with bipolar disorder are ubiquitous, under-recognized and
      suboptimally treated. Facile screening for risk factors and laboratory
      abnormalities along with behavioral modification for reducing medical comorbidity
      are warranted.

PMID- 17551360
TI  - Bibliography. Current world literature. Spondyloarthropathies.

PMID- 17551361
TI  - Spondyloarthropathies.

PMID- 17551362
TI  - Osteoporosis and vertebral fractures in ankylosing spondylitis.
AB  - PURPOSE OF REVIEW: To review recent data, in the context of what is already
      known, about an increased risk of vertebral fractures in ankylosing spondylitis
      patients. RECENT FINDINGS: Osteoporosis and fractures of the vertebral body and
      its dorsal arch are now well recognized features in patients with ankylosing
      spondylitis, but their diagnosis is still often a challenge. The risk factors and
      clinical consequences for fractures in ankylosing spondylitis are increasingly
      understood in the context of osteoimmunology and of spinal biomechanical changes
      in material and structural components in the spine that result in bone failure.
      SUMMARY: Diagnosing fractures of the vertebral body and its dorsal arch remains a
      challenge in studies and in clinical practice. Prospective studies are needed to
      evaluate to what degree such fractures can be prevented in ankylosing
      spondylitis.

PMID- 17551363
TI  - Antiinflammatory treatment with bisphosphonates in ankylosing spondylitis.
AB  - PURPOSE OF REVIEW: Bisphosphonates are antiosteoclastic agents widely used in the
      treatment of bone diseases. They also have antiinflammatory properties suggested
      by a clinical amelioration in animal models of arthritis. Bisphosphonates act on
      cells from the monocyte/macrophage lineage and may modulate the generation of
      proinflammatory cytokines. Ankylosing spondylitis is characterized by bone marrow
      subchondral inflammation with the presence of T cells and macrophages, and
      osteoporosis is a well known complication of the disease. Thus, bisphosphonates
      may be reasonably used as a therapeutic agent in ankylosing spondylitis. RECENT
      FINDINGS: Different open trials have shown that the amino bisphosphonate
      pamidronate ameliorated the clinical symptoms of ankylosing spondylitis, mainly
      axial disease, and in one study, peripheral arthritis. Laboratory parameters of
      inflammation were, in general, not influenced while biochemical markers of bone
      turnover fell significantly under pamidronate. Imaging modifications of the
      inflammatory lesions using MRI were also improved with pamidronate. A dose
      controlled study demonstrated a higher efficacy for 60 mg pamidronate compared
      with a 10 mg dose. SUMMARY: The amino bisphosphonate pamidronate has shown
      clinical and radiological amelioration in ankylosing spondylitis patients,
      although this improvement is mild and transient. Additional studies are required
      to better define the real impact of pamidronate on ankylosing spondylitis and its
      place among the different treatment options for the disease.

PMID- 17551364
TI  - Magnetic resonance imaging in ankylosing spondylitis.
AB  - PURPOSE OF REVIEW: The past 18 months has seen considerable advances in the use
      of MRI for assessment of ankylosing spondylitis, to quantify active inflammation
      in the spine and sacroiliac joints which may not otherwise be detectable and to
      therefore measure change due to therapeutic interventions. RECENT FINDINGS:
      Characterization of the extension and morphology of inflammation in ankylosing
      spondylitis is now possible with MRI techniques. A number of randomized
      controlled trials of anti-tumour necrosis factor agents in ankylosing spondylitis
      have now been published showing regression of inflammatory lesions in the spine
      by MRI. Furthermore, the role of MRI for the early diagnosis of spondyloarthritis
      has become clearer. This review discusses the techniques used, the capabilities
      and the shortcomings of MRI in assessing ankylosing spondylitis patients.
      SUMMARY: MRI techniques have implications for early identification and
      intervention in patients with ankylosing spondylitis.

PMID- 17551365
TI  - The intimate relationship between gut and joint in spondyloarthropathies.
AB  - PURPOSE OF REVIEW: The aim of this article is to highlight recent progress in the
      combined joint and gut disease in spondyloarthropathies. RECENT FINDINGS: A set
      of genes has been identified that are differentially expressed in the colon of
      spondyloarthropathy and Crohn's disease patients. Reduction of human leukocyte
      antigen B27 (HLA B27) misfolding by additional beta2-microglobulin in HLA B27
      transgenic rats unexpectedly increased disease severity, with more similarities
      to spondyloarthropathies. By contrast, colitis disappeared. SUMMARY: Human
      genomic studies combined with animal model research provide new clues concerning
      the common pathogenesis of spondyloarthropathy and Crohn's disease, further
      substantiating the unique relationship between gut and joint inflammation.

PMID- 17551366
TI  - Cardiovascular risks in spondyloarthritides.
AB  - PURPOSE OF REVIEW: Spondyloarthritides are associated with increased
      cardiovascular risks, which can only partly be explained by traditional risk
      factors. It is likely that the chronic inflammatory state is involved. In this
      review, novel findings regarding cardiac and vascular pathologies and potential
      overlapping mechanisms will be discussed. RECENT FINDINGS: Cardiac pathologies in
      spondyloarthritides are conduction disturbances and valvular heart diseases.
      Recent studies have also focused on vascular pathologies and showed impaired
      endothelial function, suggesting that atherosclerotic alterations could also be
      involved in increased cardiovascular mortality. Novel findings suggest that
      chronic systemic inflammation is involved in these cardiac and vascular
      pathologies. Thus, spondyloarthritides and ankylosing spondylitis are associated
      with increased levels of circulating inflammatory mediators such as C-reactive
      protein. Interestingly, ankylosing spondylitis patients may also have an
      atherogenic lipid profile and disturbances in their T-helper lymphocyte subsets,
      which may be involved in cardiovascular disease development. The beneficial
      effects of statin treatment on circulating inflammatory mediators and atherogenic
      lipid profiles may reveal new therapeutic options for patients with
      spondyloarthritides. SUMMARY: Recent studies have highlighted that the chronic,
      systemic inflammatory condition of patients with spondyloarthritides may be
      involved in the development of cardiac and vascular pathologies.

PMID- 17551368
TI  - New and emerging treatments for osteoporosis.
AB  - PURPOSE OF REVIEW: This review will focus on three new treatments for
      postmenopausal osteoporosis which have either been recently released (intravenous
      ibandronate), or have completed (zoledronic acid) or are currently in (denosumab)
      phase III trials. RECENT FINDINGS: A number of agents have demonstrated fracture
      risk reduction in randomized clinical trials, however, successful treatment of
      osteoporosis in the individual patient remains a challenge. Adherence to, and
      persistence with, all current osteoporosis medications are poor, being
      approximately 50% at 1 year for weekly bisphosphonates. Poor adherence to therapy
      makes it unlikely that the significant fracture reduction seen in clinical trials
      will be realized in clinical practice. SUMMARY: New therapies will not only have
      to demonstrate safety and efficacy, but also provide some advantage to patient
      persistence through either less frequent dosing schedules or elimination of
      gastrointestinal disturbances, the most common adverse effects encountered with
      bisphosphonates. This review will focus on three such agents that have either
      been recently released (intravenous ibandronate), or have completed (zoledronic
      acid) or are currently in (denosumab) phase III trials.

PMID- 17551369
TI  - An update on glucocorticoid-induced osteoporosis.
AB  - PURPOSE OF REVIEW: Glucocorticoids are widely used, often long term, and a major
      side effect is osteoporosis and increased risk of fracture. This review considers
      how common is the problem, the patients who are most at risk, our current
      understanding of mechanisms, and how to prevent and effectively treat
      glucocorticoid-induced osteoporosis. The actions currently being undertaken in
      clinical practice are reviewed. RECENT FINDINGS: Glucocorticoid-induced
      osteoporosis is an increasing problem that occurs not only in those on high-dose
      therapy. Advances in our knowledge of the cellular and cytokine mechanisms of
      bone turnover and glucocorticoid mechanisms of action are leading to a better
      understanding of how glucocorticoids affect bone cells and novel ways of
      prevention. Although there are effective treatments to prevent and control
      glucocorticoid-induced osteoporosis as well as guidelines for their use, they are
      still not being applied in routine clinical practice. SUMMARY: Glucocorticoid
      induced osteoporosis is a significant problem. Although our understanding of
      effective prevention and treatment strategies is improving, there needs to be
      better implementation of these strategies.

PMID- 17551370
TI  - The Wnt signaling pathway and bone metabolism.
AB  - PURPOSE OF REVIEW: The Wnt signaling pathway has been a major focus of effort in
      the bone field for the past 5 years. This review will examine some of the seminal
      findings that have brought us to our current understanding of the role of this
      pathway in bone metabolism. RECENT FINDINGS: The Wnt/beta-catenin signaling
      pathway has been shown to play a major role in bone cell differentiation,
      proliferation and apoptosis. It is a critical component of bone mass regulation
      and required for bone to respond to mechanical loading. The pathway is tightly
      regulated by a number of modulator proteins. Mutations in pathway components that
      result in aberrant regulation are involved in a number of bone diseases. SUMMARY:
      Understanding the role that the Wnt signaling pathways play in the regulation of
      bone metabolism offers great promise for the developmental of new paradigms and
      pharmaceutical strategies for the treatment of various diseases such as
      osteoporosis, rheumatoid arthritis and osteoarthritis. Progress in this regard
      has already been made.

PMID- 17551371
TI  - What is new in vitamin D: 2006-2007.
AB  - PURPOSE OF REVIEW: This review focuses on recent developments in a number of
      areas to bring the reader up to the current state of knowledge in this field.
      RECENT FINDINGS: A number of studies have revealed new insights into the
      regulation of the vitamin D receptor and new targets for its action. The
      mechanism by which a number of drugs can reduce circulating 25OHD has been
      clarified. New drug targets including increased bone by inhibition of
      osteoclasts, improvement in diabetes mellitus, and stimulation of innate immunity
      to combat infections such as tuberculosis have been found. SUMMARY: The wide
      distribution of the vitamin D receptor provides a number of clinical targets for
      vitamin D and its analogs. The wide distribution of CYP27B1, the enzyme required
      to convert circulating 25OHD to 1,25(OH)2D enables a number of cells to make
      their own 1,25(OH)2D3 if circulating 25OHD levels are maintained. These newer
      studies emphasize that vitamin D is not just for bones, and maintaining adequate
      levels is important for many tissues.

PMID- 17551372
TI  - Bibliography. Current world literature. Metabolic bone diseases.

PMID- 17551374
TI  - Management of intestinal involvement in systemic sclerosis.

PMID- 17551375
TI  - Treatment of small intestinal disease in systemic sclerosis with octreotide: a
      prospective study in seven patients.
AB  - BACKGROUND: Symptoms associated with small intestinal involvement in patients
      with systemic sclerosis (SSc) are usually severe and resistant to treatment.
      OBJECTIVES: To assess the safety and efficacy of octreotide in refractory small
      intestinal disease complicating SSc. METHODS: Seven female patients (aged from 37
      to 64 years old) with SSc were included in the study. All of them had symptoms
      compatible with small bowel pathology, nonresponding to several prokinetic
      agents. The patients received either subcutaneous octreotide, 0.1 mg twice daily,
      or intramuscular octreotide LAR (long-acting-release), 20 mg/mo. Symptom severity
      was assessed at baseline and at various follow-up points in a scale of 0-3, for
      each symptom. Significant gastrointestinal pathology was excluded by gastroscopy,
      colonoscopy, and small bowel enemas before octreotide administration. RESULTS:
      All patients responded to octreotide, and a significant reduction from symptom
      severity at baseline (mean +/- SD: 2.9 +/- 1.1) was noted even in the first
      following month (1.3 +/- 0.5, P = 0.0006). A significant disturbance of
      defecation in 2 patients improved dramatically. Short relapses were noticed in
      patients who were initially treated with subcutaneous octreotide. These patients
      were subsequently treated with octreotide LAR, resulting in an overall symptom
      reduction at 6 months (0.7 +/- 0.5, P = 0.003), which was sustained during follow
      up (median follow-up: 14.4 months). No side effects were noted. CONCLUSION: These
      results suggest that long-term treatment with octreotide LAR may be a safe and
      effective approach for treatment of small intestinal disease in patients with
      SSc.

PMID- 17551376
TI  - Behcet disease in adult Druzes in north Israel: the influence of ethnic origin on
      disease expression and severity.
AB  - BACKGROUND: Behcet's disease (BD) is known to vary in severity and manifestations
      in different populations. OBJECTIVE: In an attempt to sort out genetic and
      environmental influences on disease expression, we carried out a study to assess
      the clinical features of BD in the adult Druze and Arab populations in north
      Israel, comparing 2 disparate ethnic groups of similar genetic background
      inhabiting the same geographic region. METHODS: We compared 23 Druze and 30 Arab
      patients with BD. All patients fulfilled the classification criteria of the
      International Study Group for BD. RESULTS: Manifestations were similar in 2
      groups. The most frequent BD manifestations among the Druzes were recurrent oral
      aphthae (100%) and genital aphthae (61%) versus 100% and 53% in Arab patients,
      followed by inflammatory ocular involvement, 65% versus 53%, respectively.
      Arthritis was noted in 39% of Druze, with 27% in Arabs. Anterior uveitis occurred
      in 9 Druze patients (48%) and panuveitis in 4, with no case of blindness when
      compared with 30% with anterior uveitis, 4 with panuveitis, and 4 cases of
      blindness (P < 0.04) among the Arabs. One Druze BD patient had deep vein
      thrombosis versus 8 Arab patients (P < 0.017). No pulmonary embolism, aortic
      aneurysm, nor valvular involvement was documented in the Druze versus 1 case of
      each in Arabs. No case of neuro-Behcet was reported in Druzes versus 6 cases of
      neuro-Behcet among Arabs (P < 0.023). The severity score was 4.0 (SD, 1.2) in
      Druze and 5.8 (SD, 1.9) in Arabs (P = 0.0004). The prevalence of HLA B51 did not
      differ significantly between the groups. CONCLUSION: Druze BD patients in Israel
      have a milder disease than do Arabs, similar to observations in familial
      Mediterranean fever. Druze BD patients had significantly less severe ocular
      disease and neurologic manifestations. Our results suggest an ethnic influence on
      expression of BD not related to HLA B 51.

PMID- 17551377
TI  - The impact of increased body mass index on systemic lupus erythematosus: data
      from LUMINA, a multiethnic cohort (LUMINA XLVI) [corrected].
AB  - OBJECTIVE: The aim of this study was to examine the impact of an increased body
      mass index (BMI) on disease activity, damage accrual, fatigue, self-reported
      health-related quality of life (HRQOL), and fibromyalgia in patients with lupus
      using longitudinal data from LUMINA, a large multiethnic cohort. METHODS: SLE
      patients (>/=4 ACR revised criteria), </=5 years disease duration at entry into
      the cohort (T0), of Hispanic (from Texas or from the Island of Puerto Rico),
      African American, or white ethnicity were included. BMI was ascertained at T0 or
      first recorded. The average scores from all visits for disease activity (SLAM-R),
      self-reported HRQOL (physical and mental component summary measures of the SF-36)
      and fatigue (Fatigue Severity Scale), the score at last visit for damage accrual
      (SLICC Damage Index), and fibromyalgia (ACR criteria), if present at any visit,
      were examined for their association with an increased BMI by univariable and
      multivariable analyses. RESULTS: Three-hundred sixty-four patients were included;
      28% were obese (BMI >/=30 kg/m). An increased BMI was associated with older age,
      less social support, higher degree of helplessness, depression, more abnormal
      illness-related behaviors, poorer self-reported HRQOL, fatigue, and fibromyalgia,
      but not with disease activity or damage accrual by univariable analyses. In
      multivariable analyses, BMI was independently associated with fibromyalgia but
      not with disease activity, fatigue, or self-reported HRQOL. CONCLUSIONS: An
      increased BMI is independently associated with presence of fibromyalgia but not
      with disease activity, damage accrual, fatigue or self-reported quality of life
      in patients with SLE. Optimizing weight merits investigation to see if it can
      significantly impact this pervasive SLE-associated manifestation.

PMID- 17551378
TI  - Control of periodontal infection reduces the severity of active rheumatoid
      arthritis.
AB  - OBJECTIVE: To determine if eliminating periodontal infection and gingival
      inflammation affects the severity of active rheumatoid arthritis (RA) in patients
      with chronic inflammatory periodontal disease. METHODS: Twenty-nine subjects with
      confirmed diagnosis of RA and mild-to-moderate chronic periodontitis of at least
      3 years' duration were enrolled in the study. The activity of RA was assessed
      using the disease activity score test (DAS28). Seventeen subjects completing the
      study received periodontal treatment consisting of scaling/root planing and oral
      hygiene instruction; 12 subjects completing the study received no treatment.
      Participants continued their usual disease-modifying medications for RA without
      any changes in DMARD therapy during the study period. RA measurements, and
      periodontal indices were recorded at baseline and at 8 weeks for each
      participant. Mann-Whitney U and chi tests were used to test for significant
      differences in the severity of RA in the periodontally treated group compared
      with the untreated groups. RESULTS: Ten of 17 subjects (58.8%) in the treated
      group and 2 of 12 subjects (16.7%) in the untreated group showed improvement in
      RA scores. There was a statistically significant difference in DAS28 (4.3 +/- 1.6
      vs. 5.1 +/- 1.2) and erythrocyte sedimentation rate (31.4 +/- 24.3 vs. 42.7 +/-
      22) between the treatment and the control groups. CONCLUSION: Control of
      periodontal infection and gingival inflammation by scaling/root planing and
      plaque control in subjects with periodontal disease may reduce the severity of
      RA. This notion is supported by reported subjective improvement in treated
      patients.

PMID- 17551379
TI  - Transient migratory osteoporosis: rapid response to pamidronate treatment.
AB  - Transient migratory osteoporosis is characterized by the acute onset of migratory
      pain at weight-bearing joints. The diagnosis is based on clinical findings
      together with characteristic abnormalities on MRI or bone scan. Each attack is
      generally self-limiting but may take several months to resolve. We describe 2
      cases of transient migratory osteoporosis to highlight their rapid response to
      pamidronate therapy; in addition, 1 of these cases affected the sacrum, a site
      not reported to be involved in this condition.

PMID- 17551380
TI  - Extensive medium-vessel vasculitis with SLE: an unusual association.
AB  - Systemic lupus erythematosus (SLE) is a multisystem disease of autoimmune origin.
      Vasculitis is often seen with SLE, but is usually limited to small vessels alone.
      The primary pathology in SLE-related vasculitis is leukocytoclastic vasculitis.
      Medium- and large-vessel vasculitis in association with SLE is distinctly
      uncommon and is limited to occasional case reports only. In addition, reports of
      medium-vessel vasculitis with SLE generally describe involvement of a single
      vessel bed. We report a rare case of extensive vasculitis involving medium-sized
      vessels in a patient with SLE. Our patient presented with classic signs and
      symptoms of SLE and satisfied a majority of the American College of Rheumatology
      criteria for SLE. She also had toe gangrene at presentation and developed
      paraplegia during the hospital stay. Radiologic studies showed evidence of
      diffuse medium-sized vessel vasculitis. The patient was treated with monthly
      pulse cyclophosphamide and high-dose prednisolone. Follow-up showed no new
      features of vasculitis and improvement in the signs and symptoms of SLE. Her
      paraplegia showed no response to treatment. This case stresses that medium-sized
      vessel occlusion anywhere in the body can occasionally occur due to vasculitis in
      a patient with SLE.

PMID- 17551381
TI  - A case of recurrent rash and leg numbness mimicking systemic rheumatic disease:
      the occurrence of leprosy in a nonendemic area.
AB  - Leprosy, a rare chronic granulomatous communicable disease caused by
      Mycobacterium leprae, is classically known to have cutaneous and neurologic
      sequelae. As a result of immigration, the disease, endemic in Brazil, India,
      Nepal, Madagascar, Myanmar, and Indonesia, has been recognized to be present in
      North America and the Caribbean. We describe a case of a woman presenting with a
      long history of a recurrent rash and leg numbness, initially diagnosed with
      systemic lupus, who was later proven to have lepromatous leprosy. It is a
      reminder that this underappreciated disease should still be considered in the
      differential diagnosis of skin rash and neuropathy, even in nonendemic regions.

PMID- 17551382
TI  - Minocycline-induced cutaneous polyarteritis nodosa.
AB  - Minocycline is a tetracycline derivative with multiple clinical uses including
      the treatment of various infections, acne vulgaris, and rosacea. Numerous adverse
      events have been reported ranging from minor complaints such as nausea, to
      serious life-threatening toxicities such as acute renal failure, hepatotoxicity,
      and systemic lupus erythematosus. We report the case of an 18-year-old female
      patient who developed minocycline-induced cutaneous polyarteritis nodosa after
      taking minocycline for acne vulgaris. The vasculitis resolved after
      discontinuation of the minocycline without need for corticosteroids. This case is
      the eighth biopsy-confirmed case of minocycline-induced polyarteritis nodosa.
      Although minocycline is an effective medication with a wide variety of clinical
      uses, clinicians must be aware of its potential side effects including autoimmune
      related disorders such as polyarteritis nodosa or systemic lupus erythematosus.

PMID- 17551383
TI  - Strongyloides stercoralis hyperinfection in a patient with rheumatoid arthritis
      after anti-TNF-alpha therapy.
AB  - Strongyloidiasis is epidemic in tropical and subtropical regions where the
      regional prevalence may exceed 25%. In the United States, highest infection rates
      are found in immigrants. Many infected individuals are asymptomatic, whereas
      others may have mild and nonspecific cutaneous, intestinal, and pulmonary
      symptoms. Strongyloides stercoralis may remain as a dormant infection, but
      replication and dissemination can be fatal in immunocompromised patients. We
      report on a 63-year-old native Filipino man with a history of rheumatoid
      arthritis who developed Escherichia coli sepsis, filariform larvae characteristic
      of S. stercoralis bronchoalveolar lavage, and adult respiratory distress syndrome
      3 weeks after he presented with vague gastrointestinal symptoms. We believe that
      the addition of a tumor necrosis factor (TNF)-alpha inhibitor to his treatment
      with prednisone and methotrexate for rheumatoid arthritis further suppressed his
      cellular immunity leading to hyperinfection and life-threatening S. stercoralis
      infection. This is another, often latent, infection that should be considered in
      patients in or from endemic areas before institution of antitumor necrosis factor
      therapy.

PMID- 17551384
TI  - Trends in joint arthroplasty: minimally invasive surgery, wear-resistant
      materials, and biologics.

PMID- 17551386
TI  - Basic science for the clinician 44: atherosclerosis: an immunologically mediated
      (autoimmune?) disease.
AB  - There has been a sea change in our understanding of atherosclerosis. We have come
      a long way from the days where eating too much fat and not getting enough
      exercise and having the wrong genetic background was thought to be the entire
      story. A few years ago, the cardiologists began to embrace inflammation as a
      possible pathogenetic mechanism and from that came high-sensitivity C-reactive
      protein testing for just about everyone. Chronic systemic inflammation became an
      area of interest. We have learned that it is more than just corticosteroid use
      that causes accelerated atherosclerosis in our rheumatoid and lupus patients.
      Even C-reactive protein may be a pathogenetic player, not only a diagnostic clue.
      Oxidized phospholipids and the cells that recognize them may be crucial in the
      evolution of the atherosclerotic plaque. Statins may be useful in suppressing
      inflammation, not only in suppressing cholesterol levels. And now even
      cardiologists are thinking about immune mechanisms! A strange world, but the
      beneficiaries of going through this looking glass will be our patients. A true
      understanding of this seems to have required a most circuitous route-sometimes
      you have to leave for a long journey before you can return and really see home
      for the first time.

PMID- 17551387
TI  - Catastrophic acro-osteolysis of hands in systemic sclerosis.

PMID- 17551388
TI  - Low-back pain in geriatric patients: remember abdominal aortic aneurysm!

PMID- 17551389
TI  - Dramatic response of severe headaches to anticoagulation in a patient with
      antiphospholipid syndrome.

PMID- 17551390
TI  - Ankylosing spondylitis in a patient with primary hypertrophic osteoarthropathy.

PMID- 17551391
TI  - Use of adalimumab in poststreptococcal reactive arthritis.

PMID- 17551392
TI  - Development of pseudogout during etanercept treatment.

PMID- 17551393
TI  - Management of incidentally encountered nephrogenic rests.

PMID- 17551394
TI  - Ototoxicity from cisplatin therapy in childhood cancer.
AB  - Cisplatin has been associated with hearing damage. It is usually irreversible,
      bilateral, and characterized by high-frequency sensorineural hearing loss. This
      study was carried out to identify impairment of hearing function in children and
      adolescents with cancer after cisplatin therapy. Twenty-three survivors of
      childhood cancer treated with cisplatin at our Unit from 1991 to 2004 performed
      tympanometry, pure tone audiometry, transient otoacoustic emissions, and
      distortion product otoacoustic emissions (DPOAE). The median age at diagnosis was
      12.3 years and the median total dose of cisplatin received was 406 mg/m2. Fifty
      two percent of patients had bilateral and in the high frequencies range hearing
      loss on audiometry. Transient otoacoustic emission and DPOAE abnormalities were
      detected in 22% and in 71% of the patients, respectively. We found a high
      concordance between the findings of audiometry and DPOAE (P=0.01). There was no
      influence of sex and number of ototoxic drugs other than cisplatin on hearing
      loss. There was a trend for younger age and higher cumulative dose of cisplatin
      to be associated with greater severity of hearing damage. Our data provide
      further evidence on hearing damage due to cisplatin therapy in children. The high
      incidence of patients with hearing function abnormalities found in this study and
      in previous reports highlights the importance of monitoring hearing function in
      children and adolescents undergoing cisplatin therapy, or as early as possible at
      follow-up. This study also demonstrates that DPOAE should be used for screening
      of hearing abnormalities and, once hearing damage is identified, patients require
      expert audiologic pediatric evaluation and (where indicated) use of hearing aids
      and/or speech therapy.

PMID- 17551395
TI  - Nephrogenic rests: their frequency and their fate.
AB  - Nephrogenic rests (NRs) are considered to be precursor lesions of Wilms tumor,
      the most common malignant neoplasm of the urinary tract in children. We have
      previously reported on 2 cases of NRs, incidentally diagnosed at 2 to 3 months of
      age during an ultrasound mass screening for urinary tract malformations between
      1992 and 2006. As the screened population consisted of 17,065 infants, the
      observed prevalence of NRs in our area in the examined time period was of
      1.17/10,000. This is the first reliable estimate of the frequency of clinically
      appreciable NRs in infants. Microscopic NRs have been found at autopsy in about
      1% of infants. Our data are, therefore, helpful in the assessment of the
      proportion of NRs that disappear spontaneously in the childhood age group. To the
      best of our knowledge, no false-negative cases were found. Our observations
      indicate that our policy of "wait and see" is appropriate when NRs are identified
      incidentally during ultrasonographic screening done for whatever purpose.

PMID- 17551396
TI  - Predictive factors of histologic response to primary chemotherapy in patients
      with Ewing sarcoma.
AB  - A correlation between chemotherapy-induced necrosis and prognosis has been
      reported in Ewing sarcoma. To identify factors influencing histologic response
      data from 122 patients with Ewing sarcoma surgically treated were reviewed.
      Primary chemotherapy was based on vincristine, doxorubicin, cyclophosphamide,
      ifosfamide, actinomycin-D, and etoposide. Patients with complete necrosis or only
      scattered foci of viable tumor cells were good responders (GRs), the remaining
      patients poor responders (PRs). Age, sex, site and size of the tumor, fever at
      diagnosis, and lactate dehydrogenase level were clinical variables investigated.
      Mean age was 13.3+/-6 in GR and 18.1+/-9 in PR (P<0.0005); GR rate was 71% in
      patients<or=14 years, 39% in patients aged 15 to 18 years, and 26% in patient>18
      years (P=0.003). Female were more likely to achieve a GR (F 64% vs. M 42%,
      P<0.02). After multivariate analysis sex and age retained statistical
      significance. Age and sex influence the histologic response in patients with
      Ewing sarcoma.

PMID- 17551397
TI  - Intensified PEG-L-asparaginase and antimetabolite-based therapy for treatment of
      higher risk precursor-B acute lymphoblastic leukemia: a report from the
      Children's Oncology Group.
AB  - The Pediatric Oncology Group 9203 pilot protocol was designed to determine the
      feasibility of delivering 29 biweekly doses of polyethylene glycol (PEG)-L
      asparaginase, on a backbone of intensive multiagent antimetabolite-based
      consolidation and maintenance in higher risk B-precursor acute lymphoblastic
      leukemia. Between June 1992 and August 1993, 34 patients were enrolled on this
      limited institution pilot. The 5-year event-free survival (+/-standard error) and
      overall survival (+/-standard error) were 68+/-8% and 76+/-7%, respectively.
      Excessive toxicities attributed to PEG-L-asparaginase and myelosuppression
      associated with cytosine arabinoside were encountered during consolidation
      resulting in early study closure and modification of therapy for those already
      enrolled. Ninety-two percent of methotrexate/cytosine arabinoside cycles were
      associated with grades 3 to 4 myelosuppression, and 24% resulted in delays in
      therapy of more than 7 days. Fifteen PEG-L-asparaginase related toxicities
      occurred in 13 patients (8 allergy, 4 pancreas, 2 central nervous system, and 1
      hemorrhage). Intensification of therapy with PEG-L-asparaginase resulted in event
      free survival and overall survival comparable to other studies of the same time
      period without the use of agents associated with long-term complications, such as
      anthracyclines, epipodophyllotoxins, and alkylating agents. However, excessive
      toxicity occurred with intensified PEG-L-asparaginase and antimetabolite based
      therapy delivered on this schedule.

PMID- 17551398
TI  - A pre-HAART follow-up study of the hematologic manifestations in children with
      perinatal HIV-1 infection: suggestions for reclassification of clinical staging.
AB  - Hematologic manifestations in perinatally human immunodeficiency virus-1-infected
      children have not been widely described in literature. Knowledge of the
      spontaneous evolution of this disease is essential for achieving optimum care of
      patients. We analyzed the main hematologic manifestations developed in the
      prehighly active antiretroviral therapy period of 1217 children, collected from
      the Italian Register for HIV infection. In 111 patients, the hematologic sign was
      the first clinical manifestation. Among anemic and neutropenic patients, the
      fraction of patients in clinical class C was significantly higher than the
      corresponding fraction in class B (76%, P<0.001 and 74%, P<0.01), and
      significantly lower in thrombocytopenic patients (42%, P<0.001). The overall
      progression from class B to C was overlapping to the control group; when
      separated, however, anemic patients progressed faster (P<0.0001), whereas
      thrombocytopenic patients had a slower progression, similar to the nonhematologic
      patients in class A. Anemic patients had a worse prognosis than the control group
      (P<0.0001), similar to the nonhematologic patients in class C. Finally, the
      negative prognostic value of anemia was independent from the immunologic
      condition. Anemia was associated with greater mortality risks. Thrombocytopenia
      appeared, paradoxically, to be a positive prognostic factor within class B.
      Centers for Disease Control and Prevention classification presently defines
      hematologic patients as a single entity; a finer distinction could improve its
      relevance for the rational design of prevention and therapy.

PMID- 17551399
TI  - Plasma ghrelin levels in various stages of development of iron deficiency anemia.
AB  - OBJECTIVES: Ghrelin stimulates food intake and induces metabolic changes leading
      to an increase in body weight and body fat mass. Iron-deficiency anemia (IDA) is
      the most frequently seen cause of nutritional anemia, that is a type of
      starvation. There is no available study related to levels of ghrelin in IDA. The
      aim of this study is to show an association with ghrelin levels and iron
      deficiency and to demonstrate whether changes seen in iron deficiency (ID) are
      explained by ghrelin, as opposed to whether ghrelin levels correlate with ID.
      MATERIALS AND METHODS: The study group was consisted of children who were
      admitted in the outpatient clinic of pediatrics. Control group (C) was defined as
      cases with normal hemoglobin (Hb), serum iron (SI), transferrin saturation (TS),
      and ferritin (F) (>12 ng/mL) values; group hypoferritinemia (IDec) Hb: N, SI: N,
      TS: N, F<12 ng/mL; group iron deficiency (IDef), Hb: N, SI: decreased, TS<or=16%,
      F<12 ng/mL, and group IDA, Hb and SI decreased, TS<or=16%, F<12 ng/mL. The
      patients were categorized into 4 groups [group 1 (C), n=25, age=82.4+/-16.56 mo,
      F=40.87+/-6.17 ng/mL; group 2 (IDec), n=30, age=57.5+/-20.71 mo, F=29.95+/-3.77
      ng/mL; group 3 (IDef), n=28, age=50.21+/-19.87 mo, F=14.82+/-3.41 ng/mL; group 4
      (IDA), n=25, age=31.55+/-13.21 mo, F=11.75+/-4.01 ng/mL]. RESULTS: Mean value of
      ghrelin was detected to be 396.53+/-85.56 pg/mL, 332.26+/-74.35 pg/mL, 309.66+/
      68.62 pg/mL, and 177.66+/-27.81 pg/mL in control, groups IDec, IDef, and IDA,
      respectively. A statistically significant difference was detected between groups
      control and IDef (P<0.01), control and IDA, IDec and IDA, IDef and IDA (P<0.001).
      CONCLUSIONS: A significant positive correlation was demonstrated between iron
      status of the body and levels of ghrelin. Decrease in ghrelin levels in IDA can
      lead to loss of appetite, desire to eat diverse foods with resultant delay in
      growth and development.

PMID- 17551400
TI  - Mesenchymal stem cells are of recipient origin in pediatric transplantations
      using umbilical cord blood, peripheral blood, or bone marrow.
AB  - Chimerism status of bone marrow (BM)-derived mesenchymal stem cells (MSC) from
      children who received an allogeneic hematopoietic transplant is an interesting
      question, referring not only to hematopoietic transplant but also to cellular
      therapy. MSC are present in the BM but it is still controversial whether these
      cells maintain their capacity for homing to the BM. In this report, we studied
      chimerism of BM-derived MSC from children who underwent a hematopoietic stem cell
      transplant using BM, peripheral blood, and umbilical cord blood as source of
      hematopoietic stem cells.

PMID- 17551401
TI  - Magnetic resonance imaging (MRI) findings of joints in young beta-thalassemia
      major patients: fluid surrounding the scaphoid bone: a novel finding, as the
      possible effect of secondary hemochromatosis.
AB  - BACKGROUND: Beta-thalassemia major is a hereditary disease with developing
      hemochromatosis as a consequence of repeated blood transfusions. Degenerative
      arthropathy may be the first manifestation of primary hemochromatosis. OBJECTIVE:
      The aim of this study is to determine the possible effects of secondary
      hemochromatosis in joints of beta-thalassemia major patients, and to evaluate the
      sensitivity of magnetic resonance imaging (MRI) compared with plain x-ray, in the
      early diagnosis of hemochromatosis of the joints. METHODS: Thirty beta
      thalassemia major patients were randomly enrolled. A questionnaire regarding
      their history, careful physical examination, the result of their liver biopsies,
      and other necessary information were completed for these patients. X-ray and MRI
      of the left hand and wrist were taken in these patients and also in other 30
      healthy people with the same age and sex as the case control group. RESULTS: The
      prevalence of minimal fluid surrounding the scaphoid bone in MRI was 23.3%, which
      is a novel and significant finding. Other interesting changes included hypo
      signal intensity (T1 and T2) in carpal, metacarpal, radius, and ulna bones.
      CONCLUSIONS: Regarding the availability of special health services for
      thalassemia patients, this imaging study can be used for the accurate detection
      of hemochromatosis in joints of thalassemia patients.

PMID- 17551402
TI  - Expression of matrix metalloproteinases and their inhibitors in retinoblastoma.
AB  - Tumor invasion is the critical step that could lead to metastasis in
      retinoblastoma (RB), a common childhood cancer. Matrix metalloproteinases (MMPs)
      degrade extracellular matrix, which is a crucial step involved in various stages
      of tumor progression, including tumor angiogenesis, tumor growth, and also local
      invasion and subsequent distant metastasis. We investigated the role of
      extracellular MMP inducer (EMMPRIN), MMP-2, MMP-9 and tissue inhibitor of
      metalloproteinases (TIMPs): TIMP-1, TIMP-2 in RB and correlated
      clinicopathologically. Among 60 tumors, EMMPRIN was expressed in 40 (64%), MMP-2
      in 41 (66%), MMP-9 in 38 (61%), TIMP-1 in 35 (56%), and TIMP-2 in 33 (53%)
      tumors. EMMPRIN was positive (3+) in 13 (39%) out of 33 tumors with invasion and
      was positive (3+) in only 1 (3%) out of 29 tumors without invasion. MMP-2
      (P<0.0001) and MMP-9 (P<0.0001) were significantly positive (3+) in 7 (21%) and
      12 (36%) out of 33 tumors with invasion, whereas positive (3+) in 3 (10%) and
      faint (1+) in 10 (34%) tumors, respectively, out of 29 tumors without invasion.
      TIMP-1 (P<0.0001) and TIMP-2 (P=0.04) were significantly positive (3+) in 7 (21%)
      and 10 (30%), respectively out of 33 tumors with invasion, whereas positive (3+)
      in only 1 (3%) tumor each out of 29 tumors without invasion. Immunoblotting of
      tumors confirmed the presence of EMMPRIN, MMPs, and TIMPs. In conclusion, both
      MMPs and TIMPs may be involved RB invasion and EMMPRIN could play a role in up
      regulation of MMP-2 in invasive RB.

PMID- 17551403
TI  - Successful management of rhabdoid tumor of the liver.
AB  - A 3-year-old male was referred because of fever, abdominal pain, and enlarged
      abdomen. Magnetic resonance imaging showed a very large lobulated mass involving
      predominantly the right lobe of liver. Tumor histology was consistent with
      rhabdoid tumor of the liver. The patient received 3 cycles of chemotherapy
      consisting of ifosfamide, carboplatin, and etoposide alternating with
      vincristine, adriamycin, and cyclophosphamide, at 3-week intervals. Follow-up
      magnetic resonance imaging revealed approximately 84% decrease in size of tumor
      after 2 cycles of chemotherapy. Patient underwent liver transplantation, as the
      tumor was unresectable. Six weeks posttransplant, the patient received 4 more
      cycles of chemotherapy. The patient is free of disease at evaluation 3 years
      posttransplant.

PMID- 17551404
TI  - Successful treatment of an infant with constitutional chromosomal abnormality and
      hemangiopericytoma with chemotherapy alone.
AB  - Hemangiopericytoma is a rare vascular tumor, of which 5% to 10% occur in the
      pediatric population. Although usually benign in infants, local recurrence,
      metastasis, and deaths have been reported. Clonal chromosomal rearrangements have
      been described, most involving the long arm of chromosome 12. We report a case of
      a 6-month-old boy with an hemangiopericytoma of the left forearm initially
      incorrectly diagnosed as hemangioma. He was treated successfully with
      chemotherapy alone using vincristine, doxorubicin, actinomycin-D, and
      cyclophosphamide. Although cytogenetic analysis was not performed on his biopsy,
      it was later discovered that a prenatal karyotype had shown
      46,XY,inv(12)(q15q24.1).

PMID- 17551405
TI  - Aggressive systemic mastocytosis after germ cell tumor of the ovary: C-KIT
      mutation documentation in both disease states.
AB  - We report a case of aggressive systemic mastocytosis in a 3-year-old girl, who
      had undergone treatment for ovarian germ cell tumor during the previous 8 months.
      On diagnosis of systemic mastocytosis, she was treated with interferon-alpha and
      steroids. She showed tolerable side effects of interferon-alpha infusion, but
      died of multiple organ failure after 2 months of treatment. Point mutations of
      the C-KIT gene, previously implicated in the genesis of mastocytosis, were
      discovered not only in the bone marrow and the peripheral blood of the patient,
      but also in the tissue of the previously diagnosed germ cell tumor as well.

PMID- 17551406
TI  - Successfully treated acute lymphoblastic leukemia associated with
      craniopharyngioma.
AB  - The authors report a 2-year-old boy with acute lymphoblastic leukemia (ALL)
      associated with craniopharyngioma. To our knowledge, this is the first such
      report. Magnetic resonance imaging showed a suprasellar tumor, an apparent cystic
      lesion, whereas cerebral computed tomography confirmed that the tumor exhibited
      calcification. Without surgical intervention for the suprasellar tumor, we
      initiated chemotherapy for ALL. After 1 year of chemotherapy, complete remission
      was achieved, and partial resection and radiation therapy were performed on the
      suprasellar tumor. At 4 years after completing leukemia chemotherapy, the patient
      remains in complete ALL remission and has had no recurrence of craniopharyngioma.

PMID- 17551407
TI  - Acute colonic pseudo-obstruction in postchemotherapy complication of brain tumor
      treated with neostigmine.
AB  - Acute colonic pseudo-obstruction is characterized by dilatation of the large
      bowel without mechanical obstruction. Although the first step of the treatment is
      conservative management, mechanical decompression should be performed when
      symptoms persist. Recently, the efficacy of pharmacologic treatment has been
      reported in adults, but no such data have yet been reported in children for
      treatment of acute colonic pseudo-obstruction resulting from chemotherapy. We
      report a 9-year-old boy with acute colonic pseudo-obstruction caused by
      chemotherapy for brain tumor who did not respond to initial supportive therapy,
      but who was successfully treated with neostigmine.

PMID- 17551408
TI  - Ruptured Meckel diverticulum mimicking mucositis in a patient receiving induction
      therapy for high-risk acute lymphoblastic leukemia.
AB  - A Meckel diverticulum is an embryonic remnant of the vitellointestinal duct. It
      is present in approximately 2% of the population and is estimated to cause
      symptoms<5% of the time. It generally results in painless bleeding or abdominal
      pain. Rarely, it can rupture, resulting in peritonitis and gram-negative sepsis.
      We present the case of a 17-year-old male who ruptured his Meckel diverticulum 23
      days after the beginning of induction chemotherapy for high-risk acute
      lymphoblastic leukemia. We postulate that gastritis caused by dexamethasone,
      mucositis caused by doxorubicin, and the unique anatomic nature of a Meckel
      diverticulum may have contributed to this extremely unlikely and previously
      unreported event.

PMID- 17551409
TI  - Successful therapy of systemic xanthogranuloma in a child.
AB  - Systemic juvenile xanthogranuloma is a rare disease in children. A 10-year-old
      boy who showed renal, pulmonary, and liver involvement is reported. He had
      pulmonary invasion, renal mass, and nodular liver lesions but no bone
      involvement. The diagnosis was confirmed by renal biopsy, which revealed foamy,
      lipid-laden macrophages with positive CD68, but negative CD1a and S-100. The
      patient was treated with pulse high-dose methylprednisolone (10 mg/kg/d for 3 d
      for 6 courses). On 1-year follow-up period after 6 courses therapy was resulted
      in remarkable regression in renal and liver lesions.

PMID- 17551410
TI  - Quantitative assessment of mixed chimerism in allogeneic stem cell transplant
      patients: a comparison of molecular genetic and cytogenetic approaches.
AB  - After allogeneic stem cell transplantation, dual donor and recipient populations
      may be present. Donor/recipient ratio changes over time may predict clinical
      outcome: accurate measurement of these changes are needed. Chimerism may be
      measured by XY-fluorescence in situ hybridization for donor/recipient sex
      mismatch, or polymerase chain reaction amplification of short tandem repeat loci
      with donor/recipient sex match. Patients were monitored by each method.
      Additionally, mononuclear cells from 2 sex-mismatched individuals were mixed and
      analyzed using both methods. Each gave concordant estimates of patient chimerism
      and discriminated cell population ratios in mixed blood. We conclude that
      cytogenetic and molecular methods give accurate donor chimerism estimates.

PMID- 17551411
TI  - Human coronavirus OC43 pneumonia in a pediatric cancer patient with down syndrome
      and acute lymphoblastic leukemia.
AB  - In this report, we describe a case of pneumonia due to an infection with human
      coronaviruses (HCoVs)-OC43 in a pediatric leukemia patient with Down syndrome and
      febrile neutropenia. Not only the recently discovered HCoVs NL63 or HKU1 but also
      the prototype strains HCoV-OC43 and HCoV-229E have to be considered as
      respiratory pathogens in immunocompromised pediatric cancer patients. The routine
      utilization of polymerase chain reaction-based diagnostic tools would certainly
      elucidate the etiology of a relevant proportion of "pneumonias of unknown origin"
      in immunocompromised pediatric patients and would contribute to a better
      understanding of the role of HCoVs in this setting.

PMID- 17551412
TI  - Ketamine reduces the cell death following inflammatory pain in newborn rat brain.
AB  - Premature infants experience untreated repetitive pain that may alter their brain
      development. Effects of ketamine and repetitive pain on cellular death and
      subsequent behavior were studied in neonatal rats. Rat pups were randomized to
      undisturbed controls (C), 4% formalin injection (F), ketamine alone (K, 5 mg/kg)
      or formalin plus ketamine (KF) and were assessed for neuroactivation with Fos
      protein, cellular death with FluoroJade-B, cognition with the radial arm maze,
      and pain thresholds with the hot-plate. Greater Fos expression and cell death
      occurred in F vs. C groups in defined brain areas at 1 and 4 h in F compared with
      other groups. Cell death was accentuated 3.3-fold in cortical areas and 1.6-fold
      in subcortical areas in the F compared with the C group following repetitive pain
      and sacrifice 18-20 h later. These effects were ameliorated by ketamine. Compared
      with the F group, all other groups demonstrated greater exploratory and rearing
      behaviors and decreased time for bait consumption at 1-h and 3-h intervals.
      Significantly greater thermal pain latencies occurred in the KF and F groups.
      Repetitive neonatal pain accentuates neuronal excitation and cell death in
      developmentally regulated cortical and subcortical areas, which decreases the
      acquisition of visual-spatial clues, short-term and long-term memory, and
      increases pain latencies. Ketamine analgesia mitigates most of these effects.

PMID- 17551413
TI  - Measuring sex partner concurrency: it's what's missing that counts.
AB  - BACKGROUND: Sex partner concurrency is an important determinant of STI
      transmission dynamics, yet its measurement is not standardized. GOAL: : We
      assessed the agreement, compared correlates, and investigated data quality and
      completeness between 2 common concurrency measures. STUDY DESIGN: Young adults
      (ages 18-26) attending public STD clinics between 2001 and 2004 in Seattle, St.
      Louis, and New Orleans, provided data on 2 or more sex partners in a computer
      administered survey interview (N = 680). Concurrency with last partner was
      measured in 2 ways: (a) a direct question about other sexual contacts during the
      most recent sexual relationship and (b) overlapping start and end dates of the 2
      most recent relationships. RESULTS: Although 56% reported concurrency by direct
      questioning and 54% by overlapping dates, the kappa statistic for agreement
      between measures was only fair (0.395). Indeed, 29% of those reporting concurrent
      partners by the direct question did not do so by overlapping dates and 26% of
      participants concurrent by overlapping dates were not concurrent by the direct
      question. Each of the measures had dissimilar correlates, and concurrency data
      were missing or uninterpretable more often for the overlapping dates measure
      (21.3%) than the direct question (1.8%). CONCLUSIONS: Concurrency was common by
      both measures but the measures were not interchangeable. Although the overlapping
      dates measure provided information about partnership duration, it is subject to
      missing or uninterpretable data. The direct question substantially minimized the
      amount of missing data and may be more appropriate for use with computer
      administered survey interview.

PMID- 17551414
TI  - Changes in sexual behavior and STD prevalence among heterosexual STD clinic
      attendees: 1993-1995 versus 1999-2000.
AB  - OBJECTIVE: To examine trends in sex behaviors and STD prevalence over time among
      heterosexual STD clinic populations from 3 urban STD clinics in the United
      States. STUDY DESIGN: Cross-sectional analysis comparing baseline data on risk
      (self-reported) and STDs (laboratory defined) from 2 randomized controlled trials
      evaluating counseling efficacy conducted about 5 years apart, Project RESPECT
      (1993-1995) and RESPECT-2 (1999-2000). RESULTS: The participants from RESPECT (n
      = 2457) and RESPECT-2 (n = 3080) were demographically similar. However, the
      proportion of participants reporting any unprotected anal sex was much higher in
      RESPECT-2 (women: 7% vs. 18%; men: 7% vs. 17%). Also, substantially more
      participants reported a new sex partner in RESPECT-2 (women: 43% vs. 61%; men:
      54% vs. 72%). In addition, more women reported 2 or more partners (37% vs. 48%)
      and a partner with another concurrent sex partner (19% vs. 32%). Slightly more
      women and men in RESPECT-2 reported 2 protective behaviors, having an HIV test
      and any condom use; however, consistent condom use did not differ. Conversely,
      the proportion of participants with bacterial STDs (chlamydia, gonorrhea, or
      syphilis) was much lower in RESPECT-2 (women: 24% vs. 18%; men: 38% vs. 24%).
      CONCLUSIONS: Despite substantial promotion of safer sex behaviors over the past
      decade, many risk behaviors were stable over time, and some behaviors, such as
      unprotected anal sex, appeared substantially higher. Even in the absence of
      widespread behavior change, the prevalence of common bacterial STDs appeared to
      have decreased appreciably.

PMID- 17551415
TI  - Failure of nitazoxanide to cure trichomoniasis in three women.

PMID- 17551416
TI  - Correlates of acceptance of a hypothetical gonorrhea vaccine by incarcerated
      women.
AB  - OBJECTIVES: This study sought to identify correlates of acceptance of a
      hypothetical Neisseria gonorrhea (GC) vaccine in a high-risk sample of
      incarcerated women. GOALS: The goal of this study was to inform efforts to
      promote acceptance of STI vaccines in development. STUDY DESIGN: This study
      consisted of a cross-sectional survey using a structured questionnaire. RESULTS:
      The majority (79%) of incarcerated women surveyed would accept GC vaccine. In
      multivariate analyses that controlled for demographics, significant health belief
      model psychosocial correlates of higher acceptance were perceived severity of
      infection (OR = 3.33) and vulnerability to infection (OR = 2.85). Fear of
      vaccination was significantly correlated with lower acceptance (OR = 0.42).
      CONCLUSIONS: Incarcerated women's willingness to accept a hypothetical GC vaccine
      is explained by components of the health belief model and a component of the
      theory of reasoned action.

PMID- 17551417
TI  - Making a difference in palliative care nursing.

PMID- 17551418
TI  - A locally produced nutritional supplement in community-based HIV and AIDS
      patients.
AB  - This study examined the potential effect of a nutritional supplement on the
      anthropometric profiles (body measurements such as body mass index [BMI], fat
      percentage and waist-hip ratio) of HIV-positive/AIDS patients and the correlation
      between anthropometric profile, CD4+T cell count and viral load. At baseline, of
      the 35 patients recruited into the study, 32 (94.1%) showed a fat percentage
      below normal range. Twenty-four of the patients (68.6%) had a BMI within normal
      range, while a greater percentage of the patients had a normal waist-hip ratio.
      Of the 28 patients that completed the study, 26 (96.3%) reported a fat percentage
      of below 18.5%. The results showed that 19 (67.9%) of the 28 patients had a BMI
      within the normal range after nutrient intervention. There was a significant
      positive correlation between the BMI and fat percentage. At the end of the study
      the CD4+T cell count showed no correlation with any of the anthropometric indices
      while the viral load showed a significant negative correlation with the lean body
      mass and BMI. The short duration of the study probably limited the positive trend
      of the supplement.

PMID- 17551419
TI  - Process mapping: enhancing the implementation of the Liverpool Care Pathway.
AB  - Arohanui Hospice is a 12-bed specialist palliative care service based in
      Palmerston North, New Zealand. It serves a population of 180 000 people spread
      over a wide geographical area, both urban and rural. The Liverpool Care Pathway
      (LCP) was initially implemented at the hospice inpatient unit in January 2005.
      Following this, the 'LCP Pilot Project' was developed. This project involved the
      implementation of the LCP within three aged residential care facilities and two
      wards within the regional hospital. Included in the project was a research
      component to enable evaluation of the effectiveness of the LCP in each setting.
      This article will consider and demonstrate the use of process mapping (Buckman,
      2003) as a quality improvement tool to enhance the effective implementation and
      sustained use of the LCP for the dying patient within aged residential care.
      Measures are considered that support the implementation of the LCP at an
      organisational level rather than at a purely clinical level. While this work has
      been completed within the New Zealand context, it is believed that the principles
      are transferable to similar settings internationally.

PMID- 17551420
TI  - Granting death with dignity: patient, family and professional perspectives.
AB  - Dignity is a complex construct lacking clear meaning. While conceptualizing
      dignity as a basic right is useful in determining and justifying social and
      economic costs of health care, it is insufficient in considerations of personal
      dignity at the end of life. There is a dissonance between how dignity is shown to
      matter to healthcare professionals compared to patients. Furthermore, dignity is
      not clearly linked in the empirical literature to variables of quality of life
      and to a dignified death. Current studies about the construct of dignity enhance
      understanding of how we extrinsically construct moral worth, but not of how
      individuals interpret intrinsic moral worth through maintaining their personal
      integrity and attitudes of being cared for. References to key qualitative studies
      illuminate how clinicians ethically negotiate a creation of dying with dignity.
      As one's personal integrity fades, caregivers (i.e. healthcare providers, family
      and friends) are challenged to recognise and attend to the individual's
      vulnerability. I suggest that caregivers nurture personal integrity - through
      gestures that remember and honour aspects of the other as he/she was once known.
      Perhaps only through others can dying people be granted death with a sense of
      personal dignity.

PMID- 17551421
TI  - A support group programme for relatives during the late palliative phase.
AB  - This study describes an intervention where relatives were invited to take part in
      a support group programme during the late palliative phase of their family
      member. The purpose was to describe their experiences of the support group
      programme and the subsequent impact on their lives as relatives of a terminally
      ill person. Qualitative interviews were chosen as the data collection method. The
      analysis was inspired by the phenomenological method as described by Giorgi
      (1989). The relatives' experiences were categorised into six key constituents:
      confirmation; insight into the gravity of the illness; sense of belonging created
      by similar experiences; participation in the care system; being able to rest; and
      strength to provide support for the patient. These six constituents resulted in a
      sense of safety in relation to the patient, the illness, the nursing staff and
      the care unit. The study's findings show that interventions of this kind may be
      integral to the relatives' ability to handle their situation when caring for a
      terminally ill family member.

PMID- 17551422
TI  - Complementary and psychological therapies in a rural hospital setting.
AB  - The National Institute for Clinical Excellence (NICE) (2004) in the UK has led
      the way in recognising the need for a holistic approach to the support and care
      of people with cancer, with the publication of Guidance on Cancer Services:
      Improving Supportive and Palliative Care for Adults with Cancer. This article
      describes a three-year project, funded by the Big Lottery Fund through Macmillan
      Cancer Support. The project is being implemented by an art therapist, clinical
      psychologist, complementary therapist and administrator together with the
      existing team of three Macmillan nurses, an art therapist and two Macmillan
      occupational therapists. The project aims to provide a service to patients,
      carers and to the health professionals who work with people with cancer and their
      families. The service is located in a rural and Welsh-speaking area; as such,
      accessibility of the service and language choice play an important role in the
      delivery of support and treatments.

PMID- 17551423
TI  - The benefits of a palliative care network: a case study in Quebec, Canada.
AB  - This article aims to present the beneficial effects associated with the local
      implementation of an integrated network in palliative care, as perceived by
      diverse constituency groups. A case study was conducted in the province of
      Quebec, Canada, using individual (n=16) and group (n=16) interviews, with a total
      of 106 participants (i.e. managers and formal and informal caregivers). From a
      content analysis, two categories of beneficial effects emerged: those associated
      with professional practice and those with patient services. The most important
      effects of this organisational initiative were found to be the recognition of the
      palliative care domain necessitating specialized competencies, an improved
      interdisciplinary collaboration, and more efficient circulation of information
      between care settings, as well as improved accessibility, continuity and quality
      of care and services to patients at the end of life.

PMID- 17551424
TI  - Congress hots up before winding down.

PMID- 17551425
TI  - Venous leg ulcers and the VULCAN trial.

PMID- 17551426
TI  - Collaborative working to improve leg ulcer outcomes for injecting drug users.
AB  - This case study features a 37-year-old drug user with a chronic leg ulcer caused
      by injecting Heroin into his leg veins. The case study demonstrates collaborative
      working between two specialist services based in Leicester. This joint working
      and knowledge sharing has allowed for appropriate leg ulcer management in this
      erratic and vulnerable group of mainly young people. Many factors need to be
      taken into account when prescribing a dressing regimen for this group, and the
      successes and complications encountered are described.

PMID- 17551427
TI  - Assessment of wound pain: overview and a new initiative.
AB  - All wounds have the potential to cause pain, and the nature of the pain varies
      with the type of wound. Many factors may exacerbate wound pain, including
      infection, trauma at dressing changes and poor technique when applying
      compression therapy. Failure to assess wound pain or inadequate pain assessment
      can cause the patient further anguish and extended suffering. Nurses caring for
      patients with painful wounds need to identify the source of the pain and
      exacerbating factors, and determine whether it has nocicoceptive and/or
      neuropathic elements in order to optimize pain management for the individual
      patient. This article examines the assessment of wound pain and introduces an
      initiative that has been developed to improve the assessment process. The 'Heal
      not Hurt' initiative is an excellent example of the profession and industry
      working together to implement best practice guidance in patient-centred pain-free
      wound care in clinical care.

PMID- 17551428
TI  - Wound assessment and the TIME framework.
AB  - A structured wound assessment is a crucial part of managing any patient with a
      wound. Many different wound assessment tools currently exist but there is little
      standardization in the information they are used to record. A simple framework
      such as TIME can be used to co-ordinate the data collection into more useful
      elements which assist in planning cost-effective care. Clustering the information
      under the key headings of TIME encourages the practitioner to relate what they
      are seeing to what is happening at a cellular level and manage wounds in a
      proactive rather than reactive manner, setting clear management/care objectives
      to facilitate the wound to heal where this is appropriate.

PMID- 17551429
TI  - Avoiding the pitfalls and perils of catheter care.
AB  - Twelve per cent of hospital inpatients and 4% of community patients have an
      indwelling urinary catheter. Urinary catheterization increases morbidity
      threefold. The main hazards of catheterization are tissue damage, bladder damage,
      infection, encrustation and blockage. Obtaining informed consent before
      catheterization is extremely important. Restricting catheterization to those who
      clinically require this invasive procedure can reduce the number of people who
      are exposed to the hazards of catheterization. The use of silver-coated catheters
      can reduce the risk of infection and encrustation. Ensuring that practice is
      evidence-based further reduces the risks of catheterization.

PMID- 17551430
TI  - Consent and capacity 2: the Mental Capacity Act 2005 and 'living wills'.
AB  - The last article in this series discussed the social concerns which influenced
      the decision to introduce a law that laid out certain rights for certain people,
      with respect to healthcare choices, responsibilities and decisions. This, and the
      next article drawn attention to a specific aspect of the Mental Capacity Act -
      the issue of making a living will. At present, under common law, it is the legal
      right of competent adult patients to refuse medical treatments, but how is this
      achieved when, due to your illness or accident, you have lost the capacity to
      inform others of how you want your treatment to progress--or indeed that you do
      not want a certain treatment, or any treatment at all? This article discusses the
      'living will', a written legal document made by a competent person in
      anticipation of becoming ill in the future.

PMID- 17551431
TI  - Tracheostomy: facilitating successful discharge from hospital to home.
AB  - When a patient is identified as requiring a long-term or permanent tracheostomy,
      the complexity of the care needs and safety issues will dominate the focus of the
      discharge planning for the healthcare team. The effectiveness of this process
      will ultimately determine the success of the discharge and is essential in
      preventing critical incidents or readmission to hospital. An effective working
      partnership between hospital-based staff and the community team is a central
      component in achieving a successful and safe discharge. This article examines the
      discharge process from initial identification of a client requiring a long-term
      tracheostomy to the discharge itself and meeting the individual's ongoing care
      needs at home. Discharge planning considerations and clinical priorities are
      explored from both the hospital-based and community perspectives.

PMID- 17551432
TI  - Urinary elimination: Part 2--retention, incontinence and catheterization.
AB  - In part two of this article, the nursing role in relation to the assessment and
      management of urinary retention, urinary incontinence and catheterization are
      considered using recent literature and best practice statements. Retention of
      urine and incontinence have a major detrimental impact on a person's life and
      nurses have an important role to play in supporting patients. Catheterization is
      often necessary for acute retention of urine but is the last resort for
      incontinence. However, when catheter use is appropriate, asepsis technique during
      insertion and continuing management can help to minimize associated problems.
      Urinary elimination problems are embarrassing and distressing and nurses need to
      deal with them with sensitivity and empathy.

PMID- 17551433
TI  - Evaluating a framework for the development of joint appointments.
AB  - This article evaluates an evidenced-based framework for the development of joint
      appointment posts by reflecting on the lived experience. It uses an action
      science philosophy that acknowledges the development of actionable knowledge from
      the integration of theory and practice. At the same time the lived experience of
      setting up a joint appointment post is evaluated using the same evidenced-based
      framework. The actionable knowledge generated confirms the importance of
      articulating vision at strategic levels and of empowering people who are solution
      focused at operational levels.

PMID- 17551434
TI  - 'Application of cold': the BJN over 100 years ago.

PMID- 17551435
TI  - The future of nursing: career choices in potential student nurses.
AB  - Young people leaving schools and sixth-form colleges have the opportunity to
      choose a career path from an increasing number of courses in colleges of further
      and higher education. Nursing studies are now competing with a range of health
      related disciplines such as health studies, psychology and complementary therapy.
      Compared with nursing studies, many of these courses appear more exciting and
      appealing to students who are in the process of choosing a career or programme of
      study. While the increased choice is a positive move for students, it may
      contribute to the shortage of students currently entering some areas of nursing.
      Indeed, some specialties in nursing, including mental health and learning
      disabilities, are so depleted in students that they are reaching a point of
      crisis. There is also concern that recruitment into nursing remains predominately
      female and white British. Given the diversity of the UK population and the
      reliance on school leavers as a potential source of supply, it is important to
      understand why male students and those from multiracial and multicultural
      environments choose, or do not choose, nursing studies. This research study
      involved a sample of 106 16-year-old students from three secondary schools in the
      north-west and south-east of England. The questionnaire results, collected in
      schools, revealed that students held traditional views or knew very little about
      the nursing profession.

PMID- 17551436
TI  - The current constraints on nursing education.

PMID- 17551437
TI  - Progress, opportunity and unintended consequences.

PMID- 17551438
TI  - Preventing patient falls in hospital.

PMID- 17551439
TI  - Bladder pain from indwelling urinary catheterization: case study.
AB  - Indwelling urinary catheters can cause severe pain and discomfort and can impair
      a person's quality of life. Constipation can cause bladder emptying problems and
      pain if a catheter is present. If the person is constipated this should be
      treated. If there are no clinical indications for urinary catheterization the
      catheter should be removed. If the catheter is clinically necessary it may be
      possible for the person to use intermittent self-catheterization. If this is not
      possible the nurse should adopt a problem-solving approach to determine the
      reasons why pain is occurring. Ensuring that the catheter is the correct size,
      length and using an appropriate material reduces the risk of tissue damage and
      associated pain. Catheter drainage bags should be supported if used; this
      prevents traction and trauma that can lead to pain. A catheter is a foreign body
      and its presence may trigger bladder spasm and pain. This can be treated
      effectively with antimuscarinic drugs, but these should be used with caution and
      in small doses in older people. Treating bladder pain can make a huge difference
      to a person's quality of life; however, it is important to discuss treatment with
      the patient and obtain consent and respect the person's choices in relation to
      treatment.

PMID- 17551440
TI  - Integrated continence services and the female Bangladeshi population.
AB  - Continence services should be developed to cater for the needs of the entire
      population, including those of ethnic minority groups. This study undertook focus
      groups and meetings with the local Bangladeshi community and with local GPs to
      assess the needs for continence care provision and to assess current
      understanding of the problem in this community. The aim was to identify
      appropriate models for provision of care. METHOD: Questionnaires were devised
      which related to access to services for bowel and bladder problems for women and
      GPs. Focus groups which people's views and suggestions on improving service
      accessibility were ascertained. RESULTS: A 50% return was achieved for the GP
      questionnaire. GPs did not routinely enquire about bladder and bowel function and
      did not feel that Bangladeshi women needed any different service to that in the
      white population. The majority of the women in the focus groups considered
      bladder weakness as a loss of self-control, and emphasized the major impact on
      everyday life. There was little awareness of available services. CONCLUSION:
      Despite the cultural differences this study found that women tended to accept
      their bladder problem; did not consider it important enough to discuss with their
      doctor (who may also not take the problem seriously) and considered bladder
      problems as a normal part of womanhood or ageing.

PMID- 17551441
TI  - The management of lipohypertrophy in diabetes care.
AB  - Lipohypertrophy has been a recognized complication of insulin therapy for many
      years, yet research shows that its prevalence in insulin-injecting patients with
      diabetes remains high. The problem for the patient is that the injection of
      insulin into a site of lipohypertrophy, although painless, may lead to erratic
      absorption of the insulin, with the potential for poor glycaemic control and
      unpredictable hypoglycaemia. Despite the important implications of this for
      diabetes control in insulin-injecting patients, there is a dearth of information
      and completed research into the condition. This article raises awareness of
      lipohypertrophy by reviewing the available literature on the prevention,
      identification and management of the condition from a nursing perspective.
      Recommendations for medical and nursing practice in diabetes care to improve
      prevention and management of lipohypertrophy are made.

PMID- 17551442
TI  - Florence Nightingale, a force to be reckoned with: the BJN over 100 years ago.

PMID- 17551443
TI  - Developing disaster management modules: a collaborative approach.
AB  - Disasters, whether natural or human induced, can strike when least expected. The
      events of 9/11 in the US, the 7/7 bombings in the UK, and the anthrax incident in
      the US on 10th October 2001 indicate that there is a need to have a nursing
      workforce who is able to respond effectively to mass casualty events and
      incidents involving chemical, biological, radiological and nuclear substances.
      Multi-agency collaboration is one of the fundamental principles of disaster
      preparedness and response. It was therefore necessary to take a similar multi
      agency collaborative approach to develop modules on the management of mass
      casualty events and incidents involving hazardous substances. The modules are
      offered to registered nurses and registered paramedics. They can be taken
      independently or as part of a BSc in nursing or health pathway, on a part-time
      basis. Since the commencement of the modules in September 2004, registered
      paramedics and registered nurses who work in a wide range of specialties have
      accessed them.

PMID- 17551444
TI  - Renal care: six essentials for a haemodialysis patient.
AB  - Once the filtration rate of the kidney falls below 10 ml/minute a patient will
      require haemodialysis treatment sessions typically three times per week to remove
      waste products and excess fluids. Due to the obvious change in life circumstances
      the patient will require clinical intervention and usually quality psychosocial
      support. Therefore, several areas have to be included in the nursing care plan to
      provide a complete treatment strategy. Access to the blood is provided through a
      surgically created access and this must be monitored regularly for adequate
      function and signs of infection. With little or no renal function fluid will
      accumulate in the body and there are a number of clinical signs that need to be
      recognized that are involved in determining the patient's correct hydration
      status. The interpretation of routine observations such as weight and blood
      pressure is vital to the fluid removal strategy and antihypertensive drug
      therapy. The patient's diet should also be carefully controlled avoiding foods
      with high sodium, potassium and phosphate content while ensuring adequate protein
      intake and vitamin supplement where necessary. Most patients require several or
      more medications throughout their life on haemodialysis and this requires a well
      organized care plan for medication administration.

PMID- 17551445
TI  - Consent and capacity: other aspects of the Mental Capacity Act.
AB  - This article concentrates on elements of the Mental Capacity Act that may be
      glossed over when people are concentrating on the issue of living wills (advanced
      directives). New powers have been introduced under the Act and these do have the
      power to alter people's lives. A 'lasting power of attorney', for example, now
      has the power to take decisions relating to a person's health issues or welfare.
      There is a new court - the Court of Protection, designed to settle disputes about
      the validity or applicability of a living will. With the powers of a High Court,
      the Act reveals the seriousness with which the law now regards the issues that
      surround the making of a living will and the granting or refusal to grant consent
      to treatment and care.

PMID- 17551446
TI  - The information needs of men with breast cancer.
AB  - The information needs of men with breast cancer are under-researched. This
      article uses questionnaire data from 161 men with breast cancer, and in-depth
      interview data from a sample of 30 of these men, to explore perceptions of
      information needs and how best to meet these needs. These men typically received
      verbal information or written information in the form of leaflets or booklets.
      Generally this information was helpful, was pitched at about the right level and
      contained the right amount of information, but was of variable relevance given
      that it had not been developed specifically for men. Men with breast cancer would
      benefit from receiving gender-specific information, given the limitations of
      existing information sources. Of all healthcare professionals, breast care nurses
      were described as being most helpful in terms of providing both information and
      practical support.

PMID- 17551447
TI  - Impact of psychotropic medication on sexuality: literature review.
AB  - Psychotropic medication continues to be a central element in the care and
      treatment of people experiencing mental health problems. Nurses have a key role
      to play in patient education and in monitoring the benefits and side effects of
      prescribed drugs. However, evidence suggests that nurses tend to ignore or
      minimize side effects that impact on sexuality and sexual function. The focus of
      this article is on exploring the literature on psychotropic medication and sexual
      dysfunction.

PMID- 17551448
TI  - Evaluating an interview preparation process for student nurses.
AB  - The aim of this article is to share innovative practice in relation to the
      recruitment process for nurses. Quality of preparation offered to student nurses
      prior to interview was variable, therefore, a study day to equip student nurses
      with the necessary knowledge and skills for interviews was devised. The
      strategies employed include a range of teaching approaches. Student evaluation
      indicates that this interview preparation day was successful and popular, with a
      majority of students receiving immediate offers of posts. Recommendations for
      educators include addressing the recruitment process earlier within the
      curriculum and adopting some of the practises of a business school.

PMID- 17551449
TI  - Factors contributing to incidents in medicine administration. Part 1.
AB  - Part one of this two-part article explores the factors contributing to errors
      during the administration of medicines through a detailed literature review.
      Medication incidents cause serious harm to patients. In a typical NHS hospital
      approximately 7000 medication doses are administered daily (Audit Commission,
      2002a). The costs of errors to patients, practitioners and the NHS are
      significant. While some errors can be prevented, it is unlikely that they will
      ever be eliminated as they arise from human nature (Kohn et al, 2000). There is a
      lack of strong evidence in the literature about what nurses feel the factors
      contributing to medication errors are. The majority of studies were carried out
      in the USA and tended to be carried out by non-nurses with the exception of those
      by Gladstone (1995), Hand and Barber (2000) and King (2004). Gibson (2001) felt
      that nurses' experiences and knowledge appear to be undervalued.

PMID- 17551450
TI  - Student insights into the current state of the NHS.

PMID- 17551452
TI  - Specialist cardiology nurses audit post-MI community aftercare.
AB  - The transition of care into the community gives rise to the auditing and
      examination of custom and practices. This article describes how the community
      cardiology specialist nursing team at Sunderland Teaching PCT. have audited the
      practice of home visiting for acute myocardial infarction patients following
      discharge from hospital. The aim of the audit was to examine current practices
      and to consider whether or not other nursing teams have the skills to deliver
      this service thus enabling the specialist nurses to develop their skills further
      and develop nurse led initiatives to support the national service framework for
      coronary heart disease.

PMID- 17551453
TI  - Addressing the skin-care needs of the older person.
AB  - Major skin changes are one of the many features occurring with ageing and it is
      estimated that 70% of elderly people have skin problems (APGS, 2000). A report
      into skin diseases in elderly people highlighted that older people were noted to
      suffer from a lack of sensitivity to their skin care needs and related problems,
      training was lacking for healthcare professionals and service provision was not
      planned (APGS, 2000). The aim of this article is to highlight the importance of
      skin care in the older person and increase the nurse's knowledge in relation to
      the care of ageing skin; the skin changes associated with age and practical
      advice and guidance when caring for an older person's skin.

PMID- 17551454
TI  - The challenge of healthcare-associated infection outside hospital.
AB  - Infection control is an area of healthcare practice subject to rapid development
      in line with changes in the behaviour of pathogens, advances in technology, the
      altered profile of people undergoing healthcare, the settings in which that care
      is delivered and the impact of new ways of working throughout the National Health
      Service. This article describes how micro-organisms responsible for healthcare
      associated infection can be transferred between hospital and community settings
      and explains the risks of disseminating infection in relation to two types of
      pathogen carrying resistance to antibiotics: methicillin resistant Staphylococcus
      aureus and glycopeptide resistant enterococci. Ability to read current literature
      critically, to be aware of changing policy and its impact on the risk of
      infection forms an important part of the community nursing role.

PMID- 17551455
TI  - A case study looking at appropriate catheterization.

PMID- 17551456
TI  - Caring for patients with COPD and their families in the community.
AB  - Community matrons have a key role to play in the management of patients with long
      term conditions. With the expected increase in prevalence of Chronic Obstructive
      Pulmonary Disease (COPD), largely due to cigarette smoking, the management and
      care of patients with COPD is a priority for the NHS. This paper examines the
      current and future role of community matrons in the management of patients with
      COPD. Community matrons have a potential role in providing evidence based care
      and could fill a gap in the implementation of effective interventions to help
      patients and family members stop smoking. A family focused approach to assessment
      and case management are important to achieving quality care and management of
      these patients. Recommendations are made with respect to the improvement of
      service provision for individuals and families with COPD.

PMID- 17551457
TI  - Depression and older people: securing wellbeing in later life.
AB  - This article, brought to you in association with Help the Aged, looks at the
      factors that can contribute to depression in older people and highlights the
      information available from the Charity.

PMID- 17551458
TI  - Developing a career pathway within community nursing.
AB  - There has been much anxiety regarding the levels of competence and confidence of
      newly qualified nurses. This article will describe the developments within one
      primary care trust of newly qualified student nurses through to the development
      of a robust career pathway. Within this PCT previous recruitment into community
      nursing posts had been unpredictable and some newly qualified nurses had found
      the transition from pre-registration to qualified nurse within primary care very
      difficult, often choosing to pursue an alternative career pathway. This resulted
      in a high turn over of staff. It therefore became imperative that the
      organization reviewed not only its placement experience but ensured a robust
      comprehensive career pathway that supported and mapped out for nurses the
      clinical experience they could expect and support continuing professional
      development.

PMID- 17551459
TI  - Do not attempt resuscitation orders: a review of the issues.
AB  - Controversy surrounding the use of do not resuscitate orders on patients often
      without their knowledge and without apparent good reason (Age Concern England,
      2000) have led some to question the lawfulness of such orders. This article
      considers the legal basis for do not resuscitate orders and outlines best
      practice guidance that will assist district nurses and other health professionals
      in deciding whether making such an order is lawful and for the benefit of the
      patient concerned.

PMID- 17551460
TI  - Doesn't everyone matter?

PMID- 17551461
TI  - Genetic endocrine diseases. Foreword.

PMID- 17551462
TI  - New methods in genetic diagnosis including prenatal diagnosis.
AB  - Recent advances in newborn screening and molecular genetics are transforming our
      understanding of the genetic basis of diseases that affect individuals of all
      ages. It is essential for clinicians to understand the methods and goals of
      newborn screening (NBS), the principles of genetics, and the methods of molecular
      analysis including Southern blots, PCR amplification, DNA sequence analysis,
      Reverse Transcriptase PCR, Multiplex Ligation- dependent Probe Amplification
      analysis, Fluorescence in Situ Hybridization, Comparative Genomic Hybridization,
      as well as Fetal Ultrasonography. This understanding and applications of these
      tools can lead to genetic diagnoses by identifying risks from newborn screening
      results or family histories, selecting appropriate tests and understanding the
      implications of test results to the patient and their families. To facilitate
      this understanding we will review newborn screening, basic genetics, inheritance
      and examples of established and new methods used in genetic testing. It is our
      hope that this material will facilitate clinician's abilities to consider and
      detect genetic disorders so that earlier interventions and optimal outcomes can
      occur.

PMID- 17551463
TI  - Consanguinity among the Arab and Jewish populations in Israel.
AB  - Consanguineous marriages are associated with many problems, although the
      prevailing opinion is that the advantages outweigh the disadvantages. This
      explains why the custom is still extremely prevalent, particularly in Arab
      countries, India and small isolated communities. Among Israeli Arabs there has
      been a reduction in the rate of such marriages, although it is still sufficiently
      high to cause medical problems. Among Israeli Jews, the rate has always been much
      lower. Future goals are to expand the educational programs aimed at the Israeli
      Arab community and to promote the uptake of genetic counseling and prenatal
      testing where available in order to reduce the health problems even further.
      Ongoing research in order to identify specific genes will enable more conditions
      to be detectable early in pregnancy. We expect that the willingness of families
      to agree to termination of affected pregnancies will reduce the number of babies
      born with these conditions.

PMID- 17551464
TI  - Distribution of the V281L mutation of the CYP21 gene in Israeli congenital
      adrenal hyperplasia patients and its association with HLA- B14.
AB  - The V281L mutation in the CYP21 gene, responsible for non classical CAH, was
      studied in patients of different Israeli ethnic groups and compared to the data
      on healthy population. The Israeli population consists of many ethnic groups
      which can be divided into three main entities: Ashkenazi, Non Ashkenazi and
      Israeli Arabs. The frequency of V281L mutation in the patients of the different
      ethnic groups varied and was a reflection of the frequency found in the healthy
      population namely: very high in the Ashkenazi (74%) , lower in the non Ashkenazi
      (39%) and very low in the Israeli Arabs (2.9%) . The phenomenon of strong
      association between the HLA B14 allele and the V281L mutation found in our
      population study, as well as in other studies, confirmed by linkage found in
      patient families, can be used to distinguish between homozygote and hemizygote
      carrying the V281L mutation, when no family study is available. The relevance of
      this finding is especially important in cases of genetic counseling when a
      carrier of a severe mutation is involved.

PMID- 17551465
TI  - Non-classic congenital adrenal hyperplasia.
AB  - Congenital adrenal hyperplasia results from a defect in the biosynthetic pathway
      of cortisol and/or aldosterone. Non-classical ( NCAH) forms are characterized by
      milder enzyme dysfunction and manifests commonly in adolescence or adulthood. The
      most common form of NCAH is 21 hydroxylase (21-OH) deficiency. Also, a number of
      NCAH patients with 11 beta hydroxylase (11 beta-OH) deficiency have been reported
      in some populations. Although some patients with NCAH may be asymptomatic,
      hirsutism is the most common symptom. It may be clinically indistinguishable from
      PCOS. Mutations in the CYP21 (CYP21A2) gene which is located on chromosome 6p21.3
      along with a pseudogene, CYP21P (CYP21A1P), are responsible for cases of 21- OH
      deficiency. The ACTH stimulation test is the best screening test for evaluating
      adrenal gland functions. NCAH due to 21-hydroxylase deficiency is diagnosed when
      the ACTH-stimulated 17-OHP levels > 30 nmol/ l; this threshold varies depending
      on the assay. Asymptomatic patients with NCAH do not need glucocorticoid
      treatment. If the main concern of the patient is infertility, ovulation induction
      is the treatment of choice. If the patient seeks medical advice because of
      hirsutism, anti-androgens may be used. NCAH is not characterized by cortisol
      insufficiency and these patients do not need glucocorticoid replacement before
      and/or during surgery unless they have been treated chronically with
      glucocorticoids.

PMID- 17551466
TI  - 17 beta-hydroxysteroid dehydrogenase 3 deficiency in the Mediterranean
      population.
AB  - Eighty-five males with 17 beta-HSD3 were identified among a highly inbred Arab
      population in Israel and 57 studied over a period of 25 years. The founders of
      this defect originated in the mountainous regions of present Lebanon and Syria,
      but most of the families now live in Jerusalem, Hebron, the Tel-Aviv area and, in
      particular, in Gaza, where the frequency of affected males is estimated at 1 in
      100 to 150. Affected individuals are born with ambiguity of the external
      genitalia and reared as females until puberty. Thereafter marked virilization
      occurs, leading in many cases to the spontaneous adoption of a male gender
      identity and role. Adults develop a male habitus with abundant body hair and
      beard and the phallus and testes enlarge to adult proportions. Gender
      reassignment in infancy was only possible when enough erectile tissue was present
      at birth and developed into a normal size penis with testosterone. 17 beta-HSD3
      deficiency can be reliably diagnosed by endocrine evaluation and mutation
      analysis. In adults the defect is characterized by markedly increased
      concentrations of androstenedione (A) with borderline low to normal testosterone
      (T) levels and a high A/T ratio. 5a-dihydrotestosterone (DHT) concentrations are
      moderately decreased, normal or high and dehydroepiandrosterone (DHEA) levels are
      high. The estrogen pathway is also impaired, even though both estrone (E-1) and
      estradiol-17 beta (E-2) levels are high. Children have low basal levels of all
      androgens, but the defect may be demonstrated after prolonged stimulation with
      human chorionic gonadotropin (HCG). LH and FSH levels are very high after puberty
      and normal in childhood. 17 beta-HSD3 isozyme is encoded by the chromosome 9q22
      17 beta-HSD3 gene and expressed exclusively in testes. A point mutation in exon
      3, codon 80 of the 17 beta-HSD3 gene, R80Q, caused by a single base substitution
      from CGG ( arginine) to CAG ( glutamine) was identified in both alleles of 24
      individuals from 9 extended Arab families from Gaza, Jerusalem and Lod-Ramle.
      Twenty-one homozygote males (46,XY) were MPH with testicular 17 beta-HSD3
      deficiency whereas the three homozygote females (46,XX) were asymptomatic, had
      normal internal and external genitalia, normal sexual development and revealed no
      biochemical evidence of 17 beta-HSD3 deficiency. The molecular pattern is
      compatible with an autosomal recessive mode of inheritance, sex dependent.

PMID- 17551467
TI  - 5 alpha steroid reductase deficiency in Turkey.
AB  - 5 alpha steroid reductase 2 (5 alpha SR2) deficiency is an autosomal recessive
      enzyme defect causing male pseudohermaphroditism (MPH) because of an abnormally
      low peripheral conversion of testosterone to dihydrotestosterone (DHT), which is
      required for the normal differentiation of external male genitalia. The present
      report describes the distribution of 5 alpha steroid reductase gene mutations in
      the Turkish population in the light of published reports from different centers.
      Eight Turkish patients from unrelated Turkish families and a large pedigree of
      one of these patients are also discussed. These patients were followed up at
      Ankara University Department of Pediatric Endocrinology. The presence of Leu 55
      Gln mutation in six patients out of 8 indicates the increased prevalence of this
      mutation in the Turkish population with different presentations. One patient out
      of six (patient FG) had a large pedigree of Leu 55 Gln mutation in exon 1. The
      pedigree of this family with marital consanguinity was very remarkable and
      extraordinary. A further 85 members of this family were analyzed for exon 1 Leu
      55 Gln 5 alpha SR2 gene mutations. Forty two out of the 85 subjects (49.41% ) had
      this alteration in gene mutation. Thirty-one of them were heterozygous (18
      genetic male, 13 genetic female) and 11 of them were homozygous (8 genetic male,
      3 asymptomatic female carriers) for this mutation. A trinucleotid deletion at
      straddling codons 156 and 157 is responsible for a methionize residue at position
      157 (delta Met 157) of 5 alpha SR type 2 gene which was first described in our
      patient NA. Two additional Turkish patients were reported by different
      investigators with this rare mutation and this also suggests an increased
      prevalence of this mutation in the Turkish population. In conclusion Leu 55 Gln
      mutation in exon 1 seems to be a hot spot in Turkish patients. Hence 5 alpha SR2
      gene mutation analysis especially Leu 55 Gln mutation in exon 1 and delta Met 157
      in exon 3, must be evaluated in Turkish patients with male pseudohermaphroditism
      according to our results and other Turkish patients reported by different
      investigators. It is important that homozygous asymptomatic female carriers be
      taken into consideration in this clinical entity especially in closed populations
      because of the risk of carrying the disease to their offspring.

PMID- 17551468
TI  - Vitamin D receptor defects: the story of hereditary resistance to vitamin D.
AB  - Vitamin D, synthesized in the epidermis in response to UV radiation, is devoid of
      any biological activity. The hormonal activity is due to its metabolite, 1 alpha,
      25-dihydroxyvitamin D, named calcitriol. The actions of calcitriol are mediated
      by the vitamin D receptor, VDR, a member of the nuclear receptor family. The
      clinical presentation of hypocalcaemia, secondary hyperparathyroidism, early
      onset rickets in the presence of normal levels of serum 25-hydroxyvitamin D and
      markedly elevated serum levels of calcitriol is indicative of hereditary vitamin
      D resistant rickets, HVDRR. HVDRR is a recessive autosomal disorder that has been
      described in approximately 60 unrelated families. Dermal fibroblasts and
      peripheral blood lymphocytes can serve as target organ models to evaluate the
      interaction of calcitriol and its effector system. Failure of calcitriol to
      induce the enzyme 25-hydroxyvitamin D3 24 hydroxylase in fibroblasts or to
      inhibit lymphocyte mitogenesis can serve as the diagnosis for HVDRR Transfection
      studies employing site directed mutagenesis to mimic the natural mutations in
      VDR, have identified mutations that interfere with the major events in VDR
      signaling: hormone binding; heterodimerization with RXR; binding to vitamin D
      response elements in the promoters of target genes; and interaction with co-
      activators. Interference with one or more of these steps results in the clinical
      syndrome of HVDRR.

PMID- 17551469
TI  - Vitamin D receptor polymorphism in nutritional rickets.
AB  - Although the pathophysiology of rickets and especially the central role of
      Vitamin D in this disease has been clarified since the 1920s, it is not
      completely understood why rickets is still prevalant in sunny countries.
      Furthermore, as we understand more about rickets, it appears that rickets is a
      heterogeneous disorder caused by vitamin D and/or Ca deficiency. Serum 25 and
      1,25 OH vitamin D levels show a wide range of variation among children with
      rickets and the response to treatment is also variable. These observations
      suggest that individual susceptibility may play a role in the development of
      rickets. Polymorphisms in the Vitamin D receptor (VDR) gene were postulated to be
      associated with bone mineral density. VDR gene polymorphism could be influential
      in the development of rickets in some children as well. However, data in this
      regard are still scarce.

PMID- 17551470
TI  - GH1 gene deletions and IGHD type 1A.
AB  - Human Growth Hormone gene ( GH1 ) resides on chromosome 17q22-24 and it is
      expressed in somatotropic cells of the anterior pituitary gland. While there are
      multiple causes of GH Deficiency (GHD) a significant proportion have a genetic
      basis. The most severe Mendelian form of IGHD, called IGHD IA, has an autosomal
      recessive mode of inheritance. While affected individuals can have short lengths
      at birth and hypoglycemia in infancy, all develop severe dwarfism by six months
      of age. Although short stature, delayed growth velocity, and delayed skeletal
      maturation all occur with IGHD, none are specific for IGHD 1A. GH1 gene
      deletions, frameshifts, or nonsense mutations cause complete absence of GH in
      IGHD 1A. Thus IGHD 1A is best described as being complete GHD caused by severe
      loss of function GH1 gene mutations rather than being limited to only those
      having GH1 gene deletions. Interestingly, GH1 gene deletions are recurring
      mutations that can arise through unequal recombination in meiosis rather than by
      allele sharing through common descent. Individuals with IGHD 1A develop severe
      dwarfism in early infancy and often develop anti-GH antibodies after receiving
      exogenous GH. These antibodies can prevent the growth response expected from
      exogenous GH therapy. Individuals who are heterozygous for a GH1 gene deletion
      but whose other GH1 allele is not deleted and produces a non truncated product
      are usually immune tolerant.

PMID- 17551471
TI  - Genetic analysis of the pedigrees and molecular defects of the GH-receptor gene
      in the Israeli cohort of patients with Laron syndrome.
AB  - Out of the 63 patients with Laron Syndrome ( LS) followed in our clinic we were
      able to perform a genetic analysis on 43 patients belonging to 28 families.
      Twenty-seven patients were Jews, eight were Arabs, one was Druze, and six were
      Caucasians from countries other then Israel. Consanguinity was found in 11
      families. Molecular analysis of the growth hormone receptor gene was performed in
      32 patients and 32 family members. From the study of the pedigrees, as well as
      the GH receptor gene analysis, we confirmed an earlier report from our group that
      LS is a recessively inherited disease. One patient with a classical phenotype of
      LS had a non-classical pattern of inheritance: R43X heterozygosity together with
      a heterozygous polymorphism G168G; a condition which needs further exploration.

PMID- 17551472
TI  - Athyreosis, dysgenesis, and dyshormonogenesis in congenital hypothyroidism.
AB  - Congenital hypothyroidism (CH) is most commonly caused by defects in thyroid
      development leading to thyroid dysgenesis (80-90%), which consists of thyroid
      agenesis, ectopy or hypoplasia. Thyroid dysgenesis occurs mostly as a sporadic
      disease. However, a small but significant proportion of the cases are due to
      defects in transcription factors. The remaining 10-20% of congenital
      hypothyroidism is due to better-defined defects in any of the steps in the
      thyroid hormone biosynthesis, collectively called thyroid dyshormonogenesis,
      which are inherited autosomal recessively. Studying multiplex and/or
      consanguineous families with carefully defined, original phenotypes by such
      recently popular techniques as genome wide SNP genotyping with linkage search is
      likely to reveal novel disease associated genes. Thus there is new insight into
      the pathophysiology of congenital hypothyroidism.

PMID- 17551473
TI  - Multiple endocrine neoplasia type 2 and sporadic medullary thyroid carcinoma:
      Turkish experience.
AB  - Multiple endocrine neoplasia type 2 (MEN 2) is a rare autosomal dominantly
      inherited familial cancer syndrome caused by mutations in the ret proto-oncogene.
      MEN 2 has three distinct subtypes, which are MEN 2A, MEN 2B and familial
      medullary thyroid carcinoma. Identification of a disease gene has enabled a DNA
      based strategy for detection of direct mutation in patients with MEN 2 syndromes
      and in patients with sporadic medullary thyroid carcinoma. The identification of
      mutations responsible for MEN 2 syndromes has resulted in the routine
      identification of gene carriers early in life before the development of disease,
      causing timely prophylactic thyroidectomy in these patients. This report includes
      our clinical and molecular experience on Turkish MEN 2 families and patients with
      sporadic medullary thyroid carcinoma diagnosed and treated between 1994 and 2005.

PMID- 17551474
TI  - Genetics of type 1 diabetes mellitus.
AB  - Type 1 Diabetes Mellitus is a complex and polygenic disease due to gene
      environment interactions. The role of genetic background of diabetes has been
      extensively investigated. However, final conclusions have not yet been reached.
      Family and twin studies have shown that genetic factors are important
      contributors to the genetic risk of the disease. Although more than 18 diabetes
      predisposing genes have been reported to date, only the major histocompatibility
      complex (HLA) region on chromosome 6p21 (IDDM1) and the insulin gene on
      chromosome 11p15 (IDDM 2) have been conclusively associated with susceptibility
      to type 1 diabetes. However, it has been shown recently that cytotoxic lymphocyte
      antigen 4 (CTLA4) on chromosome 2q33 (IDDM12) and LYP/PTPN22 on chromosome 1p13
      also contribute to the genetic risk of T1DM. The article reviews the recent
      advances in this field. By identifying new loci or reanalyzing the known ones and
      with the help of more powerful studies, it is possible in the future to be able
      to shed more light on the complex field of the genetics of type 1 diabetes and to
      further understand the pathophysiology of the disease, which will allow us
      eventually to treat or prevent it.

PMID- 17551475
TI  - Maturity onset diabetes of the young--review.
AB  - Maturity onset diabetes of the young (MODY) is characterized by a primary defect
      in insulin secretion and hyperglycemia, nonketotic disease, monogenic autosomal
      dominant mode of inheritance, age at onset less than 25 years, and lack of auto
      antibodies. It accounts for 2-5% of all cases of non-type 1 diabetes. The
      diagnosis may be made by careful clinical evaluation, but exact subtyping is
      possible only by genetic analysis. Several genetic factors have been identified
      as causative agents in MODY, each leading to a different type of the disease.
      These include the enzyme glucokinase, which causes MODY2, and the transcription
      factors HNF- 4 alpha, TCF1, I PF-1, TCF2, and NeuroD1, which cause MODY1, 3, 4,
      5, and 6, respectively. The genetic findings have important clinical
      implications, allowing for proper genetic counseling, early diagnosis, and better
      care of patients.

PMID- 17551476
TI  - Hyperinsulinism in infancy--genetic aspects.
AB  - Hyperinsulinism in infancy (HI) is a heterogeneous disorder with respect to
      clinical presentation, genetics, histology and response to therapy. Advances in
      the understanding of the molecular basis of the disease have given the pediatric
      endocrinologists a better insight into the diagnosis and therapeutic choice. In
      50-60% of cases, a genetic etiology is unraveled. Mutations in the genes encoding
      SUR1 (ABCC8) and KIR6.2 (KCNJ11) are the most frequent genetic causes of HI
      followed by mutations in the GLUD1 gene which encodes glutamate dehydrogenase
      (GDH) enzyme. The patients with GLUD1 mutations also have hyperammonemia (HA).
      Activating dominant mutations in glucokinase (GCK) gene which result in HI are
      rare. In GLUD1 and GCK mutations the disease is usually mild, has a late onset
      and is responsive to diazoxide. However, studies so far have failed to show a
      clear genotype phenotype relation in KATP channel mutations. In conclusion the
      genetic analysis of HI has provided valuable information to the clinicians about
      the beta cell.

PMID- 17551478
TI  - At what stage of childhood obesity should the psychosocial team intervene?

PMID- 17551479
TI  - Nutritional stunting.
AB  - Nutritional stunting is a common problem of the pediatric population especially
      in developing countries. Although it is a resolvable problem, it continues to be
      an important health issue. Stunting can be diagnosed when a child's height falls
      more than two standard deviations below the mean height for age. Stunting may be
      caused by genetic, hormonal, pharmaceutical, psychosocial and nutritional
      factors. Before doing extensive laboratory tests, nutritional factors must be
      searched for at the time of diagnosis. If the etiology is nutritional deficiency,
      meticulous dietary regulation must be done. The results of treatment must be
      assessed for guiding the nutritional rehabilitation during follow up. Here we
      review the interaction of wasting and nutritional stunting; the prevalence of
      nutritional stunting; diet components and growth; the pathophysiology of
      stunting; periods of accelerated growth; the diagnosis and clinical assessment of
      nutritional stunting; the anthropometric and laboratory nutritional indices that
      can be used at the time of diagnosis and for follow-up purposes during
      rehabilitation and also the management of nutritional stunting.

PMID- 17551480
TI  - Endocrine complications of childhood cancer therapy: evaluation and management.
AB  - Endocrine complications of cancer therapy are reported in over 40% of childhood
      cancer survivors. As survival rates for childhood cancers continue to improve,
      both the incidence and prevalence of endocrinopathies directly related to cancer
      therapy will increase. To appropriately screen for and treat endocrinopathies in
      cancer survivors, pediatric endocrinologists must be aware of the differential
      pattern and severity of endocrine disturbances associated with both chemotherapy
      and radiation. Determining an individual child's risk for developing endocrine
      abnormalities requires a thorough analysis of the child's chemotherapeutic
      regimen, radiation dose, fractionation of radiotherapy, age during therapy,
      pubertal status during therapy and length of time since completion of therapy.
      The following review will identify endocrinopathies associated with different
      chemotherapy and radiation protocols and will review lifelong screening and
      treatment strategies for endocrine complications of childhood cancer.

PMID- 17551481
TI  - Traumatic brain injury and hypopituitarism in children and adolescents: is the
      problem under-estimated?
AB  - Traumatic brain injury (TBI) is the leading cause of death in children. Only
      recently, the importance of hypopituitarism as a consequence of TBI has been
      highlighted in adult patients. Data from systematic clinical studies in adults
      and patients in transition from adolescence to adulthood point to the presence of
      hypopituitarism in nearly a third of patients hospitalized for TBI. But, no
      systematic studies on posttraumatic hypopituitarism exist in children and
      adolescents. Case reports and small series of patients, however, suggest that
      children are affected to a comparable extent. Since normal pituitary function is
      required for normal growth and pubertal development in childhood, particular
      attention should be paid to this condition. The aim of this review is to
      summarize the literature on TBI and causes, clinical picture, and diagnosis of
      hypopituitarism in childhood and adolescence, underlying the relevance of the
      problem and its underestimation in clinical paediatric practice.

PMID- 17551482
TI  - Disorders of gonadal development: a broad clinical, cytogenetic and
      histopathologic spectrum.
AB  - The most complicated group of sexual differentiation disorders is that of gonadal
      development. Disorders of gonadal development form a wide clinical, cytogenetic
      and histopathological spectrum. There are still some unsolved difficulties of
      diagnosis, development of malignancy and the sex rearing of these patients. We
      reviewed 23 cases of gonadal developmental disorders among 169 patients with
      ambiguous genitalia or delayed puberty. Among 169 patients, 87 patients were
      46,XY disorders of sex development (DSD), 59 patients were 46,XX DSD without
      disorders of gonadal development and the remaining 23 patients had disorders of
      gonadal development. Nine of these 23 patients were diagnosed as 46,XY gonadal
      dysgenesis, 7 patients had ovotesticular DSD, 5 patients had 45,X/46,XY mixed
      gonadal dysgenesis. Fourteen patients with disorders of gonadal development had
      genital ambiguity, 5 patients had a female genital phenotype with a palpable
      gonad and/or delayed puberty. Four patients had the male genital phenotype.
      Disorder of gonadal development is a very important clinical problem with
      different aspects of diagnosis, treatment, rearing sex and prophylaxis. Each
      patient should be evaluated individually employing a multidiciplinary approach.

PMID- 17551483
TI  - Prevention of thyroid associated-ophthalmopathy in children and adults: current
      views and management of preventable risk factors.
AB  - Primary, secondary and tertiary prevention are defined according to the timing of
      the preventive intervention in the natural history of a disease. Secondary
      prevention in Graves' ophthalmopathy (GO) is challenging in the absence of
      reliable specific serum markers for subclinical GO that would allow an early
      diagnosis. Some risk factors for occurrence or progression of GO have been
      identified. Cigarette smoking, thyroid dysfunction and radioactive iodine (RAI)
      are known preventable risk factors. The list is probably much longer, and future
      research should be aimed at identifying more. Smoking cessation, restoration of
      euthyroidism by antithyroid drugs or L-thyroxine, glucocorticoid coverage after
      RAI or deferring RAI until the eye disease is inactive, may prevent progression
      of GO. Passive smoking seems to exacerbate autoimmune thyroid disease (AITD) in
      general, and may have a deleterious effect on childhood GO in particular,
      therefore avoidance of passive smoking is likely to be beneficial.

PMID- 17551485
TI  - Debate on the use of growth hormone in the treatment of children with idiopathic
      short stature (ISS) (Pro and Con).

PMID- 17551486
TI  - Beyond reasonable doubt: catching the growth hormone cheats.
AB  - There is widespread anecdotal evidence that growth hormone (GH) is used by
      athletes for its anabolic and lipolytic properties to improve their performance.
      Within adolescent athletes, GH may also be used to increase linear growth. The
      athletes put themselves at risk by doing so but there are also wider societal
      implications for this cheating. Although GH is on the World Anti-doping Agency
      list of banned substances, the detection of abuse with GH is challenging. Two
      approaches have been developed to detect GH abuse. The first is based on an
      assessment of the effect of exogenous GH on pituitary GH isoforms and the second
      is based on the measurement of markers of GH action. As a result GH abuse can be
      detected with reasonable sensitivity and specificity.

PMID- 17551487
TI  - Human studies of growth hormone and aging.
AB  - During the last 50 years a 20-year increase in the average life span was
      observed, and the average life span worldwide is expected to increase by another
      10 years by 2050 (1). Enhancing "healthy aging" and thus extending the time that
      the elderly are able to maintain their independence is a high priority. One of
      the major causes of dysfunction and disability in the elderly is loss of muscle
      mass and muscle strength - sarcopenia. We will review some of the aspects of
      sarcopenia in the elderly and arguments in favor and against GH replacement in
      the elderly. Since the study of Rudman and colleagues (2) was published there has
      been great interest in the role of the decline of growth hormone secretion
      observed during aging. The rationale and the basis for the hypothesis will be
      described and then we will discuss the results of clinical studies which to date
      have not demonstrated a clear clinical benefit of growth hormone replacement in
      normal aging subjects.

PMID- 17551488
TI  - The 10th International Congress of Inborn Errors of Metabolism (ICIEM) Makuhari
      Messe (Tokyo), Japan, September 2006.

PMID- 17551489
TI  - The 40th Annual Meeting of the Japanese Society for Pediatric Endocrinology
      (JSPE), Hamamatsu, Japan, 27-29 September 2006.

PMID- 17551490
TI  - HPV type-specific risks of high-grade CIN during 4 years of follow-up: a
      population-based prospective study.
AB  - We followed a population-based cohort of 5696 women, 32-38 years of age, by
      registry linkage with cytology and pathology registries during a mean follow-up
      time of 4.1 years to assess the importance for CIN2+ development of type-specific
      HPV DNA positivity at baseline. HPV 16, 31 and 33 conveyed the highest risks and
      were responsible for 33.1, 18.3 and 7.7% of CIN2+ cases, respectively. Women
      infected with HPV 18, 35, 39, 45, 51, 52, 56, 58, 59 and 66 had significantly
      lower risks of CIN2+ than women infected with HPV 16. After adjustment for
      infection with other HPV types, HPV types 35, 45, 59 and 66 had no detectable
      association with CIN2+. In summary, the different HPV types found in cervical
      cancer show distinctly different CIN2+ risks, with high risks being restricted to
      HPV 16 and its close relatives HPV 31 and HPV 33.

PMID- 17551491
TI  - The context influences doctors' support of shared decision-making in cancer care.
AB  - Most cancer patients in westernised countries now want all information about
      their situation, good or bad, and many wish to be involved in decision-making.
      The attitudes to and use of shared decision-making (SDM) by cancer doctors is not
      well known. Australian cancer clinicians treating breast, colorectal,
      gynaecological, haematological, or urological cancer were surveyed to identify
      their usual approach to decision-making and their comfort with different decision
      making styles when discussing treatment with patients. A response rate of 59%
      resulted in 624 complete surveys, which explored usual practice in discussing
      participation in decision-making, providing information, and perception of the
      role patients want to play. Univariate and multivariate analyses were performed
      to identify predictors of use of SDM. Most cancer doctors (62.4%) reported using
      SDM and being most comfortable with this approach. Differences were apparent
      between reported high comfort with SDM and less frequent usual practice.
      Multivariate analysis showed that specialisation in breast or urological cancers
      compared to other cancers (AOR 3.02), high caseload of new patients per month
      (AOR 2.81) and female gender (AOR 1.87) were each independently associated with
      increased likelihood of use of SDM. Barriers exist to the application of SDM by
      doctors according to clinical situation and clinician characteristics.

PMID- 17551492
TI  - NK-cell and T-cell functions in patients with breast cancer: effects of surgery
      and adjuvant chemo- and radiotherapy.
AB  - Breast cancer is globally the most common malignancy in women. Her2-targeted
      monoclonal antibodies are established treatment modalities, and vaccines are in
      late-stage clinical testing in patients with breast cancer and known to promote
      tumour-killing through mechanisms like antibody-dependent cellular cytotoxicity.
      It is therefore increasingly important to study immunological consequences of
      conventional treatment strategies. In this study, functional tests and four
      colour flow cytometry were used to detect natural killer (NK)-cell functions and
      receptors as well as T-cell signal transduction molecules and intracellular
      cytokines in preoperative breast cancer patients, and patients who had received
      adjuvant radiotherapy or adjuvant combined chemo-radiotherapy as well as in age
      matched healthy controls. The absolute number of NK cells, the density of NK
      receptors as well as in vitro quantitation of functional NK cytotoxicity were
      significantly higher in preoperative patients than the post-treatments group and
      controls. A similar pattern was seen with regard to T-cell signalling molecules,
      and preoperative patients produced significantly higher amounts of cytokines in
      NK and T cells compared to other groups. The results indicate that functions of
      NK and T cells are well preserved before surgery but decrease following adjuvant
      therapy, which may speak in favour of early rather than late use of
      immunotherapeutic agents such as trastuzumab that may depend on intact immune
      effector functions.

PMID- 17551493
TI  - A cohort study of dietary iron and heme iron intake and risk of colorectal cancer
      in women.
AB  - In a cohort study of 49,654 Canadian women, we assessed the association of
      colorectal cancer with total iron and heme iron intake, excluding iron
      supplements. Among women aged 40-59 years, followed for an average of 16.4 years,
      we identified 617 incident colorectal cancer cases. Data from a food frequency
      questionnaire administered at baseline were used to calculate red meat intake and
      intake of total dietary iron, iron from meat, and heme iron. Analyses were
      carried out for all cases and for the proximal colon, distal colon, and rectum,
      using Cox proportional hazards models. We found no association of intake of iron,
      heme iron, or iron from meat with risk of colorectal cancer overall or with any
      of the subsites, nor was there effect modification by alcohol consumption or
      hormonal replacement therapy.

PMID- 17551494
TI  - Newly established tumourigenic primary human colon cancer cell lines are
      sensitive to TRAIL-induced apoptosis in vitro and in vivo.
AB  - Most data on the therapeutic potential of tumour necrosis factor-related
      apoptosis-inducing ligand (TRAIL) as well as resistance to FAS ligand (FASL) in
      colorectal cancer have come from in vitro studies using cell lines. To gain a
      clearer understanding about the susceptibility of patient tumours to TRAIL and
      FASL, we derived primary human cancer epithelial cells from colon cancer
      patients. Characterisation of primary cultures PAP60 and MIH55 determined their
      highly proliferating advantage, transforming capability and tumorigenicity in
      vitro and in vivo. Although FASL treatment appeared to cause little apoptosis
      only in the PAP60 primary culture, increased apoptosis independent of p53 was
      observed in both primary PAP60 and MIH55 and control cell lines Caco-2, HT29 and
      DLD-1 after treatment with SuperKiller TRAIL. Expression analysis of death
      receptors (DR) in the original parental tumours, the primary cultures before and
      after engraftment as well as the mouse xenografts, revealed a significant
      upregulation of both DR4 and DR5, which correlated to differences in sensitivity
      of the cells to TRAIL-induced apoptosis. Treating patient tumour xenograft/SCID
      mouse models with Killer TRAIL in vivo suppressed tumour growth. This is the
      first demonstration of TRAIL-induced apoptosis in characterised tumorigenic
      primary human cultures (in vitro) and antitumour activity in xenograft models (in
      vivo).

PMID- 17551495
TI  - Prospective study of serum 25(OH)-vitamin D concentration and risk of oesophageal
      and gastric cancers.
AB  - We prospectively examined the relation between pretrial serum vitamin D status
      and risk of oesophageal and gastric cancers among subjects who developed cancer
      over 5.25 years of follow-up, including 545 oesophageal squamous cell carcinomas
      (ESCC), 353 gastric cardia adenocarcinomas, 81 gastric noncardia adenocarcinomas,
      and an age- and sex-stratified random sample of 1105 subjects. The distribution
      of serum 25(OH)D was calculated using the known sampling weights. For the cohort
      as a whole, the 25th, 50th, and 75th percentile concentrations of 25(OH)-vitamin
      D were 19.6, 31.9, and 48.7 nmol l(-1), respectively, and we found that higher
      serum 25(OH)D concentrations were associated with monotonically increasing risk
      of ESCC in men, but not in women. Comparing men in the fourth quartile of serum
      25(OH)D concentrations to those in the first, we found a hazard ratio (HR) (95%
      confidence interval (CI)) of 1.77 (1.16-2.70), P trend=0.0033. The same
      comparison in women had a HR (95% CI) of 1.06 (0.71-1.59), P trend=0.70. We found
      no associations for gastric cardia or noncardia adenocarcinoma. Among subjects
      with low vitamin D status, higher serum 25(OH)D concentrations were associated
      with significantly increased risk of ESCC in men, but not in women. Further
      refinements of the analysis did not suggest any factors, which could explain this
      unexpected result.

PMID- 17551496
TI  - A dose escalation and pharmacokinetic study of biweekly pegylated liposomal
      doxorubicin, paclitaxel and gemcitabine in patients with advanced solid tumours.
AB  - To determine the maximum tolerated doses (MTDs) and dose-limiting toxicities
      (DLTs) of pegylated liposomal doxorubicin (PLD), paclitaxel (PCX) and gemcitabine
      (GEM) combination administered biweekly in patients with advanced solid tumours.
      Twenty-two patients with advanced-stage solid tumours were treated with escalated
      doses of PLD on day 1 and PCX plus GEM on day 2 (starting doses: 10, 100 and 800
      mg m(-2), respectively) every 2 weeks. DLTs and pharmacokinetic (PK) parameters
      of all drugs were determined during the first cycle of treatment. All but six
      (73%) patients had previously received at least one chemotherapy regimen. The DLT
      dose level was reached at PLD 12 mg m(-2), PCX 110 mg m(-2) and GEM 1000 mg m(-2)
      with neutropaenia being the dose-limiting event. Of the 86 chemotherapy cycles
      delivered, grade 3 and 4 neutropaenia occurred in 20% with no cases of febrile
      neutropaenia. Non-haematological toxicities were mild. The recommended MTDs are
      PLD 12 mg m(-2), PCX 100 mg m(-2) and GEM 1000 mg m(-2) administered every 2
      weeks. The PK data revealed no obvious drug interactions. Biweekly administration
      of PLD, PCX and GEM is a well-tolerated chemotherapy regimen, which merits
      further evaluation in various types of solid tumours.

PMID- 17551497
TI  - Predictive value of chemotherapy-induced neutropenia for the efficacy of oral
      fluoropyrimidine S-1 in advanced gastric carcinoma.
AB  - Myelosuppression that occurs during chemotherapy has been reported to be a
      predictor of better survival in patients with breast or lung carcinomas. We
      evaluated the prognostic implications of chemotherapy-induced neutropenia in
      advanced gastric carcinoma. Data from a prospective survey of oral
      fluoropyrimidine S-1 for advanced gastric cancer patients in Japan were reviewed.
      We identified 1055 untreated patients with adequate baseline bone marrow
      function. During treatment with S-1, a total of 293 (28%) patients experienced
      grade 1 or higher neutropenia. The adjusted hazard ratio of death for the
      presence of neutropenia, as compared with the absence of such toxicity, from a
      multivariate Cox model was 0.72 (95% confidence interval, 0.54-0.95; P=0.0189)
      for grade 1 neutropenia, 0.63 (0.50-0.78; P<0.0001) for grade 2 neutropenia and
      0.71 (0.51-0.98; P=0.0388) for grade 3-4 neutropenia. These findings suggest that
      the occurrence of neutropenia during chemotherapy is an independent predictor of
      increased survival in patients with advanced gastric cancer, whereas the absence
      of such toxicity indicates that the dosages of drugs are not pharmacologically
      adequate. Monitoring of neutropenia in patients who receive chemotherapy may
      contribute to improved drug efficacy and favourable survival.

PMID- 17551498
TI  - Comparative analysis of xanafide cytotoxicity in breast cancer cell lines.
AB  - Xanafide, a DNA-intercalating agent and topoisomerase II inhibitor, has
      previously demonstrated comparable cytotoxicity to the parent drug amonafide (NSC
      308847). The current study was conducted to investigate further the anti
      proliferative effects of xanafide in human breast cancer cell lines, in vitro and
      in vivo. The in vitro activity of xanafide against MCF-7, MDA-MB-231, SKBR-3 and
      T47D cell lines was compared to that of paclitaxel, docetaxel, gemcitabine,
      vinorelbine and doxorubicin. In MCF-7, xanafide demonstrated comparable total
      growth inhibition (TGI) concentrations to the taxanes and lower TGI values than
      gemcitabine, vinorelbine and doxorubicin. MCF-7 (oestrogen receptor (ER)+/p53
      wild-type) was the most sensitive cell line to xanafide. MDA-MB-231 and SKBR-3
      exhibited similar sensitivity to xanafide. T47 D (ER+/p53 mutated), showed no
      response to this agent. The in vivo activity of xanafide was further compared to
      that of docetaxel in MCF-7 and MDA-MB-231 cell lines using the hollow fibre
      assay. Xanafide was slightly more potent than docetaxel, at its highest dose in
      MCF-7 cell line, whereas docetaxel was more effective than xanafide in MDA-MB-231
      cell line. Our results show that there is no relationship between sensitivity of
      these cell lines to xanafide and cellular levels of both isoforms of
      topoisomerase II and suggest that ER and p53 status and their crosstalk may
      predict the responsiveness or resistance of breast cancer patients to xanafide.

PMID- 17551499
TI  - The significance of proline-rich tyrosine kinase2 (Pyk2) on hepatocellular
      carcinoma progression and recurrence.
AB  - Understanding the precise molecular mechanisms that trigger liver cancer cell
      migration and invasion could develop novel therapeutic strategies targeting
      cancer cell invasion to increase the sensitivity to current treatment modalities.
      In the current study, 49 patients with hepatocellular carcinoma (HCC) were
      included prospectively. Liver tumour and adjacent non-tumour tissues were
      detected for the expression of Proline-rich tyrosine kinase 2 (Pyk2), focal
      adhesion kinase (FAK), ezrin and fibronectin at protein and/or gene levels.
      Correlation between the expressions of Pyk2/FAK with the clinical pathological
      data was analysed. Protein expression of Pyk2 was also examined in a nude mice
      orthotopic liver tumour model with higher metastatic potential. There were 59%
      (29 out of 49) and 57% (28 out of 49) of HCC patients with higher levels of Pyk2
      and FAK protein/gene expression, respectively. We observed a positive correlation
      between the protein and gene expression levels of Pyk2 and FAK (P=0.000,
      r=0.875). Overexpression of Pyk2 and FAK was significantly correlated with
      shorter disease-free survival. Patients with higher levels of Pyk2/FAK had larger
      tumour size and advanced Edmonson grading. In the animal studies, Pyk2
      overexpression was found in infiltrative tumour cells and lung metastatic
      nodules. In conclusion, overexpression of Pyk2 and FAK was found in nearly 60% of
      HCC patients and was significantly correlated with poor prognosis. The
      significance of Pyk2 in HCC invasiveness was confirmed by animal studies.

PMID- 17551500
TI  - Systemic cancer gene therapy using adeno-associated virus type 1 vector
      expressing MDA-7/IL24.
AB  - Melanoma differentiation-associated gene-7/interleukin-24 (mda-7/IL24),
      selectively induces apoptosis in cancer cells without harming normal cells. It
      also exerts immunomodulatory and antiangiogenic effects, as well as potent
      antitumor bystander effects, making it an ideal candidate for a new anticancer
      gene therapy. Here, we examined the feasibility of adeno-associated virus type 1
      (AAV1) vector-mediated systemic gene therapy using mda-7/IL24. In vitro studies
      showed that medium conditioned by AAV1-mda7-transducedC2C12 cells induces tumor
      cell-specific apoptosis and inhibits angiogenesis in a human umbilical vein
      endothelial cell tube formation assay. To assess the in vivo effects of AAV1
      mediated systemic delivery of MDA-7/IL24, we generated a subcutaneous tumor model
      by injecting Ehrlich ascites tumor cells into the dorsum of DDY mice. A single
      intravenous injection of AAV1-mda7 (2.0 x 10(11) viral genomes) significantly
      inhibited tumor growth. In addition, terminal deoxynucleotidyl transferase
      mediated dUTP nick-end labeling (TUNEL), and immunohistochemical analyses showed
      significant induction of tumor-cell-specific apoptosis and reduction of
      microvessel formation within the tumors, and there was a significant increase in
      survival among the AAV1-mda7-treated mice. These results clearly demonstrate that
      continuous systemic delivery of MDA-7/IL24 can serve as an effective treatment
      for cancer. Thus, AAV1 vector-mediated systemic delivery of MDA-7/IL24 represents
      a potentially important new approach to anticancer therapy.

PMID- 17551501
TI  - Restoration of SMN function: delivery of a trans-splicing RNA re-directs SMN2 pre
      mRNA splicing.
AB  - Spinal muscular atrophy (SMA) is caused by loss of survival motor neuron-1
      (SMN1). A nearly identical copy gene called SMN2 is present in all SMA patients;
      however SMN2 produces low levels of functional protein due to alternative
      splicing. Recently a therapeutic approach has been developed referred to as trans
      splicing. Conceptually, this strategy relies upon pre-messenger RNA (pre-mRNA)
      splicing occurring between two separate molecules: (i) the endogenous target RNA
      and (ii) the therapeutic RNA that provides the correct RNA sequence via a trans
      splicing event. SMN trans-splicing RNAs were initially examined and expressed
      from a plasmid-backbone and shown to re-direct splicing from a SMN2 mini-gene as
      well as from endogenous transcripts. Subsequently, recombinant adeno-associated
      viral vectors were developed that expressed and delivered trans-splicing RNAs to
      SMA patient fibroblasts. In the severe SMA patient fibroblasts, SMN2 splicing was
      redirected via trans-splicing to produce increased levels of full-length SMN mRNA
      and total SMN protein levels. Finally, small nuclear ribonucleoprotein (snRNP)
      assembly, a critical function of SMN, was restored to SMN-deficient SMA
      fibroblasts following treatment with the trans-splicing vector. Together these
      results demonstrate that the alternatively spliced SMN2 exon 7 is a tractable
      target for replacement by trans-splicing.

PMID- 17551502
TI  - Chemotherapy enhances CD8(+) T cell-mediated antitumor immunity induced by
      vaccination with vaccinia virus.
AB  - The use of immunotherapy or chemotherapy alone is generally ineffective against
      well-established tumors. To overcome this intrinsic resistance against therapy
      for tumors, we have attempted to combine immunotherapy with chemotherapy. In this
      study, we tried to induce a rapid antitumor effect via chemoimmunotherapy using a
      vaccinia viral vaccine as an immunotherapeutic agent with anticancer agents
      including epigallocatechin-3-gallate (EGCG) and conventional anticancer drugs.
      Although a combination of vaccinia-mediated vaccination and chemotherapy led to a
      strong inhibition of tumor growth, monotherapy alone failed to completely cure
      tumors. In contrast, intravenous injection of cisplatin (CDDP) or
      cyclophosphamide (CTX) after vaccinia virus vaccination led to complete
      regression of the established tumors. Interestingly, anticancer drugs appear to
      augment the antitumor effect of the vaccinia virus-mediated immunotherapy. This
      effect is mainly associated with the enhanced tumor-specific CD8(+) T cell immune
      response induced by vaccinia virus, which was demonstrated by antibody depletion.
      However, anticancer drugs alone failed to induce a significant enhancement of the
      tumor-specific CD8(+) T cell immune response. Taken together, these results
      suggest that combining vaccinia virus-based immunotherapy with anticancer drugs
      is particularly effective against established tumors by increasing the tumor
      antigen-specific CD8(+) T cell immune response, which is primed by vaccinia virus
      mediated vaccination.

PMID- 17551503
TI  - Lentiviral-mediated expression of polysialic acid in spinal cord and conditioning
      lesion promote regeneration of sensory axons into spinal cord.
AB  - In adult mammals, sensory axons that regenerate in the dorsal root are unable to
      grow across the dorsal root entry zone (DREZ) into the spinal cord. In this study
      we examined whether, by inducing expression of polysialic acid (PSA) (a large
      carbohydrate attached to molecules on the cell surface), in the spinal cord by
      lentiviral vector (LV) delivery of polysialyltransferase (PST), DREZ could be
      rendered permeable to regenerating sensory axons. High-level PSA expression was
      observed in astrocytes and many other cell types after LV/PST injection into the
      spinal cord. In animals receiving LV/PST injection in combination with a
      conditioning lesion, many axons penetrated the DREZ following L4-5 dorsal
      rhizotomy. Some axons reached lamina IV-V and extended rostrally and caudally in
      the degenerating dorsal column. In LV/green fluorescent protein (GFP)-injected
      animals, most of the regenerating axons were halted before DREZ, even with a
      conditioning lesion. More Schwann cells migrated into the LV/PST-transduced
      spinal cord, many of them accompanying the regenerating axons. A Schwann cell
      astrocyte-dorsal root ganglion (DRG) neuron co-culture experiment confirmed that
      induced PSA expression on astrocytes facilitates the crossing of DRG axons from
      Schwann cells to astrocytes. These data suggest that over-expression of PSA can
      create a favorable condition for regenerating axons, and that this approach could
      form part of a combinational therapeutic strategy for promoting the repair of
      central nervous system (CNS) injuries.

PMID- 17551504
TI  - Bone regeneration by regulated in vivo gene transfer using biocompatible polyplex
      nanomicelles.
AB  - Gene therapy is a promising strategy for bone regenerative medicine. Although
      viral vectors have been intensively studied for delivery of osteogenic factors,
      the immune response inevitably inhibits bone formation. Thus, safe and efficient
      non-viral gene delivery systems are in high demand. Toward this end, we developed
      a polyplex nanomicelle system composed of poly(ethyleneglycol) (PEG)-block
      catiomer (PEG-b-P[Asp-(DET)]) and plasmid DNA (pDNA). This system showed little
      cytotoxicity and excellent transfection efficiency to primary cells. By the
      transfection of constitutively active form of activin receptor-like kinase 6
      (caALK6) and runt-related transcription factor 2 (Runx2), the osteogenic
      differentiation was induced on mouse calvarial cells to a greater extent than
      when poly(ethylenimine) (PEI) or FuGENE6 were used; this result was due to low
      cytotoxicity and a sustained gene expression profile. After incorporation into
      the calcium phosphate cement scaffold, the polyplex nanomicelles were
      successfully released from the scaffold and transfected surrounding cells.
      Finally, this system was applied to in vivo gene transfer for a bone defect model
      in a mouse skull bone. By delivering caALK6 and Runx2 genes from nanomicelles
      incorporated into the scaffold, substantial bone formation covering the entire
      lower surface of the implant was induced with no sign of inflammation at 4 weeks.
      These results demonstrate the first success in in vivo gene transfer with
      therapeutic potential using polyplex nanomicelles.

PMID- 17551505
TI  - Toll-like receptors impact on safety and efficacy of gene transfer vectors.
AB  - Innate immune responses are triggered when pattern-recognition receptors
      recognize specific conserved patterns on pathogens. The most extensively studied
      pattern-recognition receptors are toll-like receptors (TLRs), which are comprised
      of 11 different receptors, named TLR1-11. TLRs recognize motifs that are found on
      a wide range of pathogens, and activation of TLRs results in the production of
      large amounts of type I interferons and several proinflammatory cytokines. These
      cytokine responses are important in controlling pathogen replication and they
      also provide an initiation signal for the adaptive immune response. Although
      numerous manuscripts have reviewed the important role of TLRs in host defense
      against wild-type viruses, bacteria, and/or their subcomponents, none have
      focused on how TLRs recognize commonly utilized gene delivery vehicles such as
      adenovirus and adeno-associated virus (AAV) vectors. In this review, we discuss
      our understanding of how TLRs are activated by gene transfer vectors.

PMID- 17551506
TI  - Development of renal-targeted vectors through combined in vivo phage display and
      capsid engineering of adenoviral fibers from serotype 19p.
AB  - The potential efficacy of gene delivery is dictated by the infectivity profile of
      existing vectors, which is often restrictive. In order to target cells and organs
      for which no efficient vector is currently available, a promising approach would
      be to engineer vectors with novel transduction profiles. Applications that
      involve injecting adenovirus (Ad) vectors into the bloodstream require that
      native tropism for the liver be removed, and that targeting moieties be
      engineered into the capsid. We previously reported that pseudotyping the Ad
      serotype 5 fiber for that of Ad19p results in reduced hepatic transduction. In
      this study we show that this may be caused, at least in part, by a reduction in
      the capacity of the Ad19p-based virus to bind blood coagulation factors. It is
      therefore a potential candidate for vector retargeting, focusing on the kidney as
      a therapeutic target. We used in vivo phage display in rats, and identified
      peptides HTTHREP and HITSLLS that homed to the kidneys following intravenous
      injection. We engineered the HI loop of Ad19p to accommodate peptide insertions
      and clones. Intravenous delivery of each peptide-modified virus resulted in
      selective renal targeting, with HTTHREP and HITSLLS-targeted viruses selectively
      transducing tubular epithelium and glomeruli, respectively. Our study has
      important implications for the use of genetic engineering of Ad fibers to produce
      targeted gene delivery vectors.

PMID- 17551507
TI  - Replication-competent adenovirus-mediated suicide gene therapy with radiation in
      a preclinical model of pancreatic cancer.
AB  - In preparation for a Phase I trial, we evaluated the efficacy and toxicity of
      replication-competent adenovirus-mediated suicide gene therapy in combination
      with radiation in a preclinical model of pancreatic cancer. Human MiaPaCa-2 and
      PANC-1 pancreatic adenocarcinoma cells were found to be sensitive to the
      oncolytic effects of the Ad5-yCD/mutTK(SR39)rep-ADP adenovirus and also to the
      cytotoxic effects of the yeast cytosine deaminase (yCD) and herpes simplex virus
      thymidine kinase (HSV-1 TK(SR39)) genes in vitro. Combining Ad5
      yCD/mutTK(SR39)rep-ADP-mediated suicide gene therapy with radiation significantly
      increased tumor control beyond that of either modality alone. Injection of Ad5
      yCD/mutTK(SR39)rep-ADP in the dog pancreas at doses (10(12) virus particle (vp))
      to be used in humans resulted in mild pancreatitis but not peritonitis or
      hepatotoxicity. Following administration of 9-(4-[(18)F]-fluoro-3
      hydroxymethylbutyl)guanine ([(18)F]-FHBG), a positron-emitting substrate of HSV-1
      TK, Ad5-yCD/mutTK(SR39)rep-ADP activity could be monitored non-invasively by
      positron emission tomography (PET). [(18)F]-FHBG uptake was readily detected in
      the pancreas but not in other major abdominal organs, indicating that little of
      the injected adenovirus disseminates to collateral tissues. These results
      demonstrate that Ad5-yCD/mutTK(SR39)rep-ADP-mediated suicide gene therapy has the
      potential to augment the effectiveness of pancreatic radiotherapy without
      resulting in excessive toxicity. Hence they provide the scientific basis for an
      ongoing Phase I trial in pancreatic cancer.

PMID- 17551508
TI  - Antagonism of myostatin enhances muscle regeneration during sarcopenia.
AB  - A reduction in muscle mass and strength is often observed with aging, and this
      phenomenon is known as sarcopenia. This age-related atrophy frequently correlates
      with insufficient levels of muscle regeneration resulting from impairment of
      satellite cell involvement and myogenesis brought about by the aged environment.
      Using myostatin-null mice, we recently showed that negative regulators of muscle
      mass such as myostatin play an active role in the regulation of myogenesis during
      aging. The present study specifically tests the therapeutic value of a myostatin
      antagonist in sarcopenia. We report here that a short-term blockade of myostatin,
      through stage-specific administration of a myostatin antagonist, significantly
      enhanced muscle regeneration in aged mice after injury and during sarcopenia.
      Antagonism of myostatin led to satellite cell activation, increased Pax7 and MyoD
      protein levels, and greater myoblast and macrophage cell migration, resulting in
      enhanced muscle regeneration after notexin injury in aged mice. In addition, the
      antagonist demonstrated a high degree of efficacy, as only minimal doses during
      the critical period of regeneration after injury were sufficient to restore the
      myogenic and inflammatory responses in the aged environment. Thus, we propose
      that the antagonism of myostatin has significant therapeutic potential in the
      alleviation of sarcopenia.

PMID- 17551509
TI  - The environmental fate of organic pollutants through the global microbial
      metabolism.
AB  - The production of new chemicals for industrial or therapeutic applications
      exceeds our ability to generate experimental data on their biological fate once
      they are released into the environment. Typically, mixtures of organic pollutants
      are freed into a variety of sites inhabited by diverse microorganisms, which
      structure complex multispecies metabolic networks. A machine learning approach
      has been instrumental to expose a correlation between the frequency of 149 atomic
      triads (chemotopes) common in organo-chemical compounds and the global capacity
      of microorganisms to metabolise them. Depending on the type of environmental fate
      defined, the system can correctly predict the biodegradative outcome for 73-87%
      of compounds. This system is available to the community as a web server
      (http://www.pdg.cnb.uam.es/BDPSERVER). The application of this predictive tool to
      chemical species released into the environment provides an early instrument for
      tentatively classifying the compounds as biodegradable or recalcitrant. Automated
      surveys of lists of industrial chemicals currently employed in large quantities
      revealed that herbicides are the group of functional molecules more difficult to
      recycle into the biosphere through the inclusive microbial metabolism.

PMID- 17551510
TI  - Transcriptional responses to fatty acid are coordinated by combinatorial control.
AB  - In transcriptional regulatory networks, the coincident binding of a combination
      of factors to regulate a gene implies the existence of complex mechanisms to
      control both the gene expression profile and specificity of the response.
      Unraveling this complexity is a major challenge to biologists. Here, a novel
      network topology-based clustering approach was applied to condition-specific
      genome-wide chromatin localization and expression data to characterize a dynamic
      transcriptional regulatory network responsive to the fatty acid oleate. A network
      of four (predicted) regulators of the response (Oaf1p, Pip2p, Adr1p and Oaf3p)
      was investigated. By analyzing trends in the network structure, we found that two
      groups of multi-input motifs form in response to oleate, each controlling
      distinct functional classes of genes. This functionality is contributed in part
      by Oaf1p, which is a component of both types of multi-input motifs and has two
      different regulatory activities depending on its binding context. The dynamic
      cooperation between Oaf1p and Pip2p appears to temporally synchronize the two
      different responses. Together, these data suggest a network mechanism involving
      dynamic combinatorial control for coordinating transcriptional responses.

PMID- 17551511
TI  - Ubiquitination screen using protein microarrays for comprehensive identification
      of Rsp5 substrates in yeast.
AB  - Ubiquitin-protein ligases (E3s) are responsible for target recognition and
      regulate stability, localization or function of their substrates. However, the
      substrates of most E3 enzymes remain unknown. Here, we describe the development
      of a novel proteomic in vitro ubiquitination screen using a protein microarray
      platform that can be utilized for the discovery of substrates for E3 ligases on a
      global scale. Using the yeast E3 Rsp5 as a test system to identify its substrates
      on a yeast protein microarray that covers most of the yeast (Saccharomyces
      cerevisiae) proteome, we identified numerous known and novel ubiquitinated
      substrates of this E3 ligase. Our enzymatic approach was complemented by a
      parallel protein microarray protein interaction study. Examination of the
      substrates identified in the analysis combined with phage display screening
      allowed exploration of binding mechanisms and substrate specificity of Rsp5. The
      development of a platform for global discovery of E3 substrates is invaluable for
      understanding the cellular pathways in which they participate, and could be
      utilized for the identification of drug targets.

PMID- 17551512
TI  - The economics of synthetic biology.

PMID- 17551513
TI  - The adapter importin-alpha provides flexible control of nuclear import at the
      expense of efficiency.
AB  - Although there exists a large family of nuclear transport receptors
      (Karyopherins), the majority of known import cargoes use an adapter protein,
      Importin-alpha (Impalpha), which links the cargo to a karyopherin, Importin-beta
      (Impbeta). The reason for the existence of transport adapters is unknown. One
      hypothesis is that, as Impalpha re-export is coupled to GTP hydrolysis, it can
      drive a higher concentration of nuclear cargo than could be achieved by direct
      cargo binding to Importin-beta. However, computer simulations predicted the
      opposite outcome, and showed that direct transport is faster than adapter
      mediated transport. These predictions were validated experimentally. The data,
      together with previous analyses of nuclear protein import, suggest that the use
      of adapters such as importin-alpha provides the cell with increased dynamic range
      for control of nuclear import rates, but at the expense of efficiency.

PMID- 17551515
TI  - Intracellular amyloid-beta in Alzheimer's disease.
AB  - The primal role that the amyloid-beta (Abeta) peptide has in the development of
      Alzheimer's disease is now almost universally accepted. It is also well
      recognized that Abeta exists in multiple assembly states, which have different
      physiological or pathophysiological effects. Although the classical view is that
      Abeta is deposited extracellularly, emerging evidence from transgenic mice and
      human patients indicates that this peptide can also accumulate intraneuronally,
      which may contribute to disease progression.

PMID- 17551516
TI  - Lessons from 50 years of SOS DNA-damage-induced mutagenesis.
AB  - This historical perspective integrates 50 years of research on SOS mutagenesis in
      Escherichia coli with the proverbial '3R' functions--replication, repair and
      recombination--that feature DNA polymerase V. Genetic and biochemical data are
      assimilated to arrive at a current picture of UV-damage-induced mutagenesis. An
      unprecedented DNA polymerase V transactivation mechanism, which involves the RecA
      protein, sheds new light on unresolved issues that have persisted over time,
      prompting us to reflect on evolving molecular concepts regarding DNA structures
      and polymerase-switching mechanisms.

PMID- 17551517
TI  - Intermediate filaments: from cell architecture to nanomechanics.
AB  - Intermediate filaments (IFs) constitute a major structural element of animal
      cells. They build two distinct systems, one in the nucleus and one in the
      cytoplasm. In both cases, their major function is assumed to be that of a
      mechanical stress absorber and an integrating device for the entire cytoskeleton.
      In line with this, recent disease mutations in human IF proteins indicate that
      the nanomechanical properties of cell-type-specific IFs are central to the
      pathogenesis of diseases as diverse as muscular dystrophy and premature ageing.
      However, the analysis of these various diseases suggests that IFs also have an
      important role in cell-type-specific physiological functions.

PMID- 17551518
TI  - A comprehensive screen for SNP associations on chromosome region 5q31-33 in
      Swedish/Norwegian celiac disease families.
AB  - Celiac disease (CD) is a gluten-induced enteropathy, which results from the
      interplay between environmental and genetic factors. There is a strong human
      leukocyte antigen (HLA) association with the disease, and HLA-DQ alleles
      represent a major genetic risk factor. In addition to HLA-DQ, non-HLA genes
      appear to be crucial for CD development. Chromosomal region 5q31-33 has
      demonstrated linkage with CD in several genome-wide studies, including in our
      Swedish/Norwegian cohort. In a European meta-analysis 5q31-33 was the only region
      that reached a genome-wide level of significance except for the HLA region. To
      identify the genetic variant(s) responsible for this linkage signal, we performed
      a comprehensive single nucleotide polymorphism (SNP) association screen in 97
      Swedish/Norwegian multiplex families who demonstrate linkage to the region. We
      selected tag SNPs from a 16 Mb region representing the 95% confidence interval of
      the linkage peak. A total of 1,404 SNPs were used for the association analysis.
      We identified several regions with SNPs demonstrating moderate single- or
      multipoint associations. However, the isolated association signals appeared
      insufficient to account for the linkage signal seen in our cohort. Collective
      effects of multiple risk genes within the region, incomplete genetic coverage or
      effects related to copy number variation are possible explanations for our
      findings.

PMID- 17551519
TI  - Mimulus is an emerging model system for the integration of ecological and genomic
      studies.
AB  - The plant genus Mimulus is rapidly emerging as a model system for studies of
      evolutionary and ecological functional genomics. Mimulus contains a wide array of
      phenotypic, ecological and genomic diversity. Numerous studies have proven the
      experimental tractability of Mimulus in laboratory and field studies. Genomic
      resources currently under development are making Mimulus an excellent system for
      determining the genetic and genomic basis of adaptation and speciation. Here, we
      introduce some of the phenotypic and genetic diversity in the genus Mimulus and
      highlight how direct genetic studies with Mimulus can address a wide spectrum of
      ecological and evolutionary questions. In addition, we present the genomic
      resources currently available for Mimulus and discuss future directions for
      research. The integration of ecology and genetics with bioinformatics and genome
      technology offers great promise for exploring the mechanistic basis of adaptive
      evolution and the genetics of speciation.

PMID- 17551520
TI  - Invasion success of the bumblebee, Bombus terrestris, despite a drastic genetic
      bottleneck.
AB  - In early 1992, the European bumblebee, Bombus terrestris, was first seen in
      Tasmania and currently has spread to most of the island. Here, we report on the
      genetic structure, using micro-satellites, of the invading population from
      samples collected in the years 1998-2000, a few years after the first sighting of
      the species in its new area. The data show that the Tasmanian population has a
      very low genetic diversity, with less than half of the allelic richness
      (Richness=2.89 alleles; H(exp)=0.591) and lower levels of heterozygosity as
      compared to populations in New Zealand (4.24 alleles; H(exp)=0.729) and Europe
      (5.08 alleles; H(exp)=0.826). In addition, the genetic data suggest that the
      invasion must have happened once, probably around late 1991, and was the result
      of very few, perhaps only two, individuals arriving in Tasmania. Furthermore,
      these founders came from the New Zealand population. Today, the population in the
      south of Tasmania seems to act as a source population from which individuals
      migrate into other parts of the state. A similar source-sink structure seems also
      the case for New Zealand. The data show that B. terrestris is a highly invasive
      species capable of establishing itself even after a dramatic genetic bottleneck.
      B. terrestris may be an invasive species due to the haplo-diploid sex
      determination system, which exposes recessive, deleterious mutations to
      selection. Offspring of such purged lines may then be able to tolerate high
      levels of inbreeding.

PMID- 17551521
TI  - Diversity and evolution of the Mhc-DRB1 gene in the two endemic Iberian
      subspecies of Pyrenean chamois, Rupicapra pyrenaica.
AB  - Major histocompatibility complex class II locus DRB variation was investigated by
      single-strand conformation polymorphism analysis and sequence analysis in the two
      subspecies of Pyrenean chamois (Rupicapra pyrenaica) endemic to the Iberian
      Peninsula. Low levels of genetic variation were detected in both subspecies, with
      seven different alleles in R. p. pyrenaica and only three in the R. p. parva.
      After applying the rarefaction method to cope with the differences in sample
      size, the low allele number of parva was highlighted. The low allelic repertoire
      of the R. p. parva subspecies is most likely the result of bottlenecks caused by
      hunting pressure and recent parasitic infections by sarcoptic mange. A
      phylogenetic analysis of both Pyrenean chamois and DRB alleles from 10 different
      caprinid species revealed that the chamois alleles form two monophyletic groups.
      In comparison with other Caprinae DRB sequences, the Rupicapra alleles displayed
      a species-specific clustering that reflects a large temporal divergence of the
      chamois from other caprinids, as well as a possible difference in the selective
      environment for these species.

PMID- 17551522
TI  - Low mitochondrial variability in birds may indicate Hill-Robertson effects on the
      W chromosome.
AB  - Interference among loci subject to selection (the Hill-Robertson effect) may
      considerably reduce levels of adaptation and variability in genomic regions that
      lack recombination. Y- or W chromosomes are particularly vulnerable to such
      effects, since they represent large, non-recombining blocks of genetic material.
      In birds, the W chromosome and mitochondrial genomes are both maternally
      transmitted, and hence fail to recombine with each other, whereas in mammals the
      Y chromosome is paternally transmitted. We show here that mitochondrial DNA
      sequence diversity is reduced in non-ratite birds compared with mammals. After
      considering possible confounding factors, such as differences in generation
      times, mutation rates and demography, we conclude that Hill-Robertson effects
      associated with the W chromosome provide the most likely explanation for this
      difference.

PMID- 17551523
TI  - An excess of nonsynonymous polymorphism and extensive haplotype structure at the
      PtABI1B locus in European aspen (Populus tremula): a case of balancing selection
      in an obligately outcrossing plant?
AB  - Here, we describe an unusually pronounced haplotype structure at the PtABI1B
      locus in the obligately outcrossing tree Populus tremula. Both nucleotide
      diversity and divergence at PtABI1B was low compared to other P. tremula genes
      suggesting that the gene is located in a region with a low mutation rate. Despite
      this, PtABI1B shows a very marked excess of nonsynonymous polymorphisms across
      the entire coding region and linkage disequilibrium (LD) extending across the
      entire PtABI1B region of approximately 2.6 kb. Such extensive LD is normally not
      seen in P. tremula. The extensive LD at PtABI1B is caused by the presence of two
      distinct haplotypes. The haplotype structure is not caused by a lack of
      recombination in the region, because evidence of recombination can be detected.
      In addition, several statistical tests strongly reject neutrality for the PtABI1B
      region, suggesting that the unusual haplotype structure could be actively
      maintained by balancing selection.

PMID- 17551524
TI  - Genomics, environmental genomics and the issue of microbial species.
AB  - A microbial species concept is crucial for interpreting the variation detected by
      genomics and environmental genomics among cultivated microorganisms and within
      natural microbial populations. Comparative genomic analyses of prokaryotic
      species as they are presently described and named have led to the provocative
      idea that prokaryotes may not form species as we think about them for plants and
      animals. There are good reasons to doubt whether presently recognized prokaryotic
      species are truly species. To achieve a better understanding of microbial
      species, we believe it is necessary to (i) re-evaluate traditional approaches in
      light of evolutionary and ecological theory, (ii) consider that different
      microbial species may have evolved in different ways and (iii) integrate genomic,
      metagenomic and genome-wide expression approaches with ecological and
      evolutionary theory. Here, we outline how we are using genomic methods to (i)
      identify ecologically distinct populations (ecotypes) predicted by theory to be
      species-like fundamental units of microbial communities, and (ii) test their
      species-like character through in situ distribution and gene expression studies.
      By comparing metagenomic sequences obtained from well-studied hot spring
      cyanobacterial mats with genomic sequences of two cultivated cyanobacterial
      ecotypes, closely related to predominant native populations, we can conduct in
      situ population genetics studies that identify putative ecotypes and functional
      genes that determine the ecotypes' ecological distinctness. If individuals within
      microbial communities are found to be grouped into ecologically distinct, species
      like populations, knowing about such populations should guide us to a better
      understanding of how genomic variation is linked to community function.

PMID- 17551525
TI  - Modelling the maintenance of male-fertile cytoplasm in a gynodioecious
      population.
AB  - Gynodioecy is the co-occurrence of females and hermaphrodites in populations. It
      is usually due to the combined action of cytoplasmic male sterility (CMS) genes
      and nuclear genes that restore male fertility. According to previous theoretical
      studies, it is very difficult to explain the maintenance of gynodioecy with CMS
      and male-fertile cytotypes, although it has been observed in some species.
      However, only very specific situations have been investigated so far. We present
      a model to investigate the conditions that promote the maintenance of this
      breeding system in the case of an outcrossed species when CMS and male-fertile
      (non-CMS) cytotypes are present in an infinite panmictic population. We show that
      the type of cost of restoration strongly affects the conditions for stable
      maintenance of gynodioecy. Stable nuclear-cytoplasmic gynodioecy requires a
      female advantage, which is a classical condition for gynodioecy, but also a cost
      of CMS for female fitness, which had been rarely investigated. A cost of
      restoration is also needed, which could affect either pollen or seeds. Finally,
      we found that gynodioecy was attainable for a large set of parameter values,
      including low differences in fitness among genotypes and phenotypes. Our
      theoretical predictions are compared with previous theoretical work and with
      results of empirical studies on various gynodioecious species.

PMID- 17551526
TI  - No genetic correlation between the sexes in mating frequency in the bean beetle,
      Callosobruchus chinensis.
AB  - Female multiple mating, which is common in animals, may have evolved not in
      response to fitness advantages to females but as a genetic corollary to selection
      on males to mate frequently. This nonadaptive hypothesis assumes a genetic
      correlation between females and males in mating frequency, which has received a
      few empirical investigations. We tested this hypothesis by observing the
      correlated response in male mating frequency in the adzuki bean beetle,
      Callosobruchus chinensis to artificial selection on female propensity to remate.
      Compared to control females, females from lines selected for increased or
      decreased female propensity to remate had, respectively, higher or lower mating
      frequency measured by the number of mating within a given period. This indicates
      that female receptivity to remating is genetically correlated with female mating
      frequency, and thus the artificial selection for female propensity to remate
      influenced female mating frequency. In contrast, males from the selected lines
      that diverged in female mating frequency did not vary significantly in their
      mating frequency. These results indicate that there is no genetic correlation
      between the sexes in mating frequency in C. chinensis. This study shows that the
      reason why females in C. chinensis remate despite suffering fitness costs cannot
      be explained by indirect selection resulting from selection on males to mate
      multiple times.

PMID- 17551527
TI  - Diploid males sire triploid daughters and sons in the parasitoid wasp Cotesia
      vestalis.
AB  - In the Hymenoptera, males develop as haploids from unfertilized eggs and females
      develop as diploids from fertilized eggs. In species with complementary sex
      determination (CSD), however, diploid males develop from zygotes that are
      homozygous at a highly polymorphic sex locus or loci. We investigated mating
      behavior and reproduction of diploid males of the parasitoid wasp Cotesia
      vestalis (C. plutellae), for which we recently demonstrated CSD. We show that the
      behavior of diploid males of C. vestalis is similar to that of haploid males,
      when measured as the proportion of males that display wing fanning, and the
      proportion of males that mount a female. Approximately 29% of diploid males sired
      daughters, showing their ability to produce viable sperm that can fertilize eggs.
      Females mated to diploid males produced all-male offspring more frequently (71%)
      than females mated to haploid males (27%). Daughter-producing females that had
      mated to diploid males produced more male-biased sex ratios than females mated to
      haploid males. All daughters of diploid males were triploid and sterile. Three
      triploid sons were also found among the offspring of diploid males. It has been
      suggested that this scenario, that is, diploid males mating with females and
      constraining them to the production of haploid sons, has a large negative impact
      on population growth rate and secondary sex ratio. Selection for adaptations to
      reduce diploid male production in natural populations is therefore likely to be
      strong. We discuss different scenarios that may reduce the sex determination load
      in C. vestalis.

PMID- 17551528
TI  - Allelic penetrance approach as a tool to model two-locus interaction in complex
      binary traits.
AB  - Many binary phenotypes do not follow a classical Mendelian inheritance pattern.
      Interaction between genetic and environmental factors is thought to contribute to
      the incomplete penetrance phenomena often observed in these complex binary
      traits. Several two-locus models for penetrance have been proposed to aid the
      genetic dissection of binary traits. Such models assume linear genetic effects of
      both loci in different mathematical scales of penetrance, resembling the
      analytical framework of quantitative traits. However, changes in phenotypic scale
      are difficult to envisage in binary traits and limited genetic interpretation is
      extractable from current modeling of penetrance. To overcome this limitation, we
      derived an allelic penetrance approach that attributes incomplete penetrance to
      the stochastic expression of the alleles controlling the phenotype, the genetic
      background and environmental factors. We applied this approach to formulate
      dominance and recessiveness in a single diallelic locus and to model different
      genetic mechanisms for the joint action of two diallelic loci. We fit the models
      to data on the genetic susceptibility of mice following infections with Listeria
      monocytogenes and Plasmodium berghei. These models gain in genetic
      interpretation, because they specify the alleles that are responsible for the
      genetic (inter)action and their genetic nature (dominant or recessive), and
      predict genotypic combinations determining the phenotype. Further, we show via
      computer simulations that the proposed models produce penetrance patterns not
      captured by traditional two-locus models. This approach provides a new analysis
      framework for dissecting mechanisms of interlocus joint action in binary traits
      using genetic crosses.

PMID- 17551531
TI  - The advent of the cytokine storm.

PMID- 17551532
TI  - The urologist as a gatekeeper.

PMID- 17551533
TI  - Losing the kingdom: the case against commercial organ donation.

PMID- 17551534
TI  - Kidney donation and rewarded gifting: an Iranian model.

PMID- 17551535
TI  - Drug insight: the use of bisphosphonates for the prevention and treatment of
      osteoporosis in men.
AB  - Osteoporosis has long been recognized as a disease affecting postmenopausal women
      but it has become increasingly clear that men are affected by low bone density
      and suffer the consequences of osteoporotic fractures. Men attending clinical
      urological practices might be at raised risk of bone loss due to hypogonadism,
      either identified during work-up of erectile dysfunction or induced by androgen
      deprivation therapy for treatment of prostate cancer. The availability of
      bisphosphonate drugs with proven efficacy in fracture reduction has
      revolutionized osteoporosis therapy in the past decade. The use of these agents
      has been traditionally based on data obtained predominantly from postmenopausal
      women and cases of glucocorticoid-induced osteoporosis, but data are becoming
      increasingly available to justify their use in men. Despite the availability and
      favorable safety profile of bisphosphonates, many patients are not receiving
      therapy. This article serves to review the data regarding bisphosphonate use in
      men, discussing particularly the pharmacology and mechanisms of action of these
      agents, and findings from clinical studies supporting their use for fracture
      prevention.

PMID- 17551536
TI  - Mechanisms of disease: high-grade prostatic intraepithelial neoplasia and other
      proposed preneoplastic lesions in the prostate.
AB  - High-grade prostatic intraepithelial neoplasia (HGPIN) is the most likely
      precursor of prostatic adenocarcinoma according to virtually all available
      evidence. This lesion is characterized by cellular proliferations within pre
      existing ducts and acini, with nuclear and nucleolar enlargements similar to
      those seen in prostate cancer, although unlike cancer HGPIN retains a basal-cell
      layer. The recognition of HGPIN is clinically important because of the strong
      association between this disease and prostatic carcinoma. The predictive value
      for cancer of an initial diagnosis of HGPIN on needle biopsy has substantially
      declined, with values falling from 36% to 21%. A major factor contributing to
      this decline is related to increased use of needle biopsy core sampling, which
      has provided the means for many cancers associated with HGPIN to be detected on
      initial biopsy; repeat biopsy, even with good sampling, does not detect many
      additional cancers. Other possible findings in the prostate might indicate
      premalignant disease (low-grade prostatic intraepithelial neoplasia, atrophy,
      malignancy-associated changes, and atypical adenomatous hyperplasia or adenosis),
      but the data for these premalignant diseases are much less convincing than those
      for HGPIN.

PMID- 17551537
TI  - Therapy insight: prophylaxis, monitoring and treatment of perioperative
      myocardial ischemia with emphasis on urological surgery.
AB  - Unrecognized or silent perioperative myocardial ischemia is common in patients
      who undergo high-risk surgery, including cystectomy, and could predict cardiac
      morbidity and mortality in postoperative patients. This disorder is not merely a
      marker of extensive coronary disease but has a close association with
      perioperative myocardial infarction (PMI). In a review of published data,
      including meta-analyses, in the context of high-risk urological surgery, up to
      50% of PMIs were found to go unrecognized if only clinical signs and symptoms are
      considered. Prevention and treatment of these previously unrecognized cardiac
      events might significantly reduce long-term morbidity and mortality. The
      emergence of reliable markers of PMI, such as increased levels of troponin I,
      could help in the detection of events that would have otherwise remained
      unnoticed. In this Review we examine the effect of these developments in the
      context of high-risk urological surgery. Changes to preoperative assessment,
      perioperative management, and prophylaxis of PMI are critically assessed. We
      performed a prospective audit using postoperative troponin I levels to assess the
      rate of silent perioperative myocardial ischemia and infarction. An increasingly
      proactive attitude towards perioperative monitoring for myocardial ischemia and
      infarction has evolved, and postoperative serial screening with troponin I might
      be beneficial in high-risk patients undergoing major urological surgery.

PMID- 17551538
TI  - A case of florid cystitis glandularis.
AB  - BACKGROUND: A 32-year-old healthy woman from China was diagnosed with a bladder
      mass during pelvic ultrasonography, carried out during the work-up of a
      miscarriage. Cystoscopy by the Department of Obstetrics and Gynecology confirmed
      the presence of a bladder mass, after which she was referred to our department
      for evaluation and management. The patient was asymptomatic at presentation. She
      denied urologic symptoms and did not have a history of smoking or industrial
      exposure to carcinogens. INVESTIGATIONS: Laboratory test results and urine
      studies were unremarkable. Cytology revealed benign cells with numerous micro
      organisms. Intravenous pyelography revealed a 1 x 2 cm filling defect in the mid
      posterior bladder compatible with a mass. There were no upper urinary tract
      defects. We performed cystoscopy with transurethral resection of the bladder
      tumor. DIAGNOSIS: Pathology revealed cystitis glandularis. MANAGEMENT: The
      patient was followed up with repeat cystoscopy after 4 months; there was no
      evidence of recurrence. She was scheduled for surveillance after a further 3
      months, but was lost to follow-up.

PMID- 17551539
TI  - Behavioral and neural effects of nicotine on visuospatial attentional reorienting
      in non-smoking subjects.
AB  - The cholinergic neurotransmitter system has been proposed to be involved in the
      processing of probabilistic top-down information provided by endogenous cues in
      location-cueing paradigms. It has been shown that the behavioral and neural
      effects of a nicotinic cholinergic stimulation resemble the effects obtained by
      manipulating the validity of the spatial cues: enhancing cortical nicotine levels
      and decreasing cue validity both reduce the reaction time difference between
      invalidly and validly cued targets (ie, the 'validity effect') as well as neural
      activity related to attentional reorienting in parietal brain regions. In the
      present study, we investigated whether the behavioral and neural effects of
      nicotine in location-cueing paradigms are dependent upon different a priori cue
      validities. Twenty-four subjects were investigated in a double-blind placebo
      controlled between-subject design with functional magnetic resonance imaging.
      Nicotine was administered to non-smoking volunteers via polacrilex gums
      (Nicorette, 2 mg) before performing a location-cueing paradigm with valid and
      invalid cues in the context of 90 and 60% cue validity in the MR scanner.
      Nicotine significantly reduced the validity effect in the 90% but not in the 60%
      cue validity condition. Fronto-parietal and cingulate regions showed stronger
      nicotinic reductions of reorienting-related neural activity in the high than in
      the low cue validity condition. Our data reveal an interaction effect between the
      pharmacological and cognitive modulation of attentional reorienting, which is
      evident at both a behavioral as well as the neuronal level.

PMID- 17551541
TI  - Augmented acquisition of cocaine self-administration and altered brain glucose
      metabolism in adult female but not male rats exposed to a cannabinoid agonist
      during adolescence.
AB  - Marijuana consumption during adolescence has been proposed to be a stepping-stone
      for adult cocaine addiction. However, experimental evidence for this hypothesis
      is missing. In this work we chronically injected male and female Wistar rats with
      either the cannabinoid agonist CP 55,940 (CP; 0.4 mg/kg) or its corresponding
      vehicle. Adult acquisition (seven 30 min daily sessions) and maintenance
      (fourteen 2 h daily sessions) of cocaine self-administration (1 mg/kg), food
      reinforced operant learning under conditions of normal (ad libitum access to
      food), and high motivation (food-restriction schedule) were measured.
      Additionally, brain metabolic activity was analyzed by means of [(18)F]
      fluorodeoxyglucose positron emission tomography. During the acquisition phase,
      female CP-treated rats showed a higher rate of cocaine self-administration as
      compared to vehicle-treated females and males; no differences were found between
      both male groups. This effect disappeared in the maintenance phase. Moreover, no
      differences among groups were evident in the food-reinforced operant task,
      pointing to the cocaine-specific nature of the effect seen in self-administration
      rather than a general change in reward processing. Basal brain metabolic activity
      also changed in CP-treated females when compared to their vehicle-treated
      counterparts with no differences being found in the males; more specifically we
      observed a hyper activation of the frontal cortex and a hypo activation of the
      amygdalo-entorhinal cortex. Our results suggest that a chronic exposure to
      cannabinoids during adolescence alters the susceptibility to acquire cocaine self
      administration, in a sex-specific fashion. This increased susceptibility could be
      related to the changes in brain metabolic activity induced by cannabinoids during
      adolescence.

PMID- 17551540
TI  - Repeated lipopolysaccharide (LPS) or cytokine treatments sensitize ethanol
      withdrawal-induced anxiety-like behavior.
AB  - Previous investigations demonstrated that repeated stresses before an ethanol
      exposure sensitize ethanol withdrawal-induced anxiety-like behavior ('anxiety').
      In addition to activating the hypothalamic-pituitary-adrenal axis, acute stress
      also elevates cytokines in brain. Initially, to test possible cytokine
      involvement in this stress/withdrawal protocol, cytokines were increased in brain
      with 2 weekly repeated lipopolysaccharide (LPS) administrations (1000 microg/kg)
      [corrected] (LPS/withdrawal protocol) or with twice weekly
      intracerebroventricular (i.c.v.) administrations of the cytokines IL-1 beta, CCL2
      (MCP-1) or TNFalpha (cytokine/withdrawal protocol) before exposure and withdrawal
      from a 5-day cycle of chronic ethanol diet. Both protocols sensitized withdrawal
      induced anxiety and confirm cytokine involvement in the sensitized anxiety
      response. Testing of various doses of LPS (16-1000 microg/kg) and TNFalpha (3-100
      ng, i.c.v.) demonstrated the dose-related nature of these protocols to sensitize
      withdrawal-induced anxiety. The sensitized anxiety was not produced by a single 5
      day ethanol diet cycle or by repeated LPS or cytokine treatments alone. Likewise,
      sensitized anxiety in these protocols could not be attributed to differences in
      ethanol ingestion. When challenged with a subsequent re-exposure to a 5-day
      ethanol diet cycle 16 days after completion of the LPS/withdrawal or
      cytokine/withdrawal protocols, an increase in withdrawal-induced anxiety was
      observed-an indication of induction of an underlying persistent adaptive change.
      Finally, just as found previously with the stress/withdrawal protocol,
      administration of the benzodiazepine receptor antagonist flumazenil before the
      LPS or TNF treatments prevented anxiety sensitization. Together, these findings
      indicate that increased cytokine activity induces adaptive change that supports
      sensitization of ethanol withdrawal-induced anxiety that may be linked to GABA(A)
      receptor function.

PMID- 17551542
TI  - Chronic nicotine self-administration augments hypothalamic-pituitary-adrenal
      responses to mild acute stress.
AB  - We investigated the effect of chronic nicotine self-administration (SA) on
      hypothalamic-pituitary-adrenal (HPA) hormonal responses to acute stressors. Adult
      male Sprague-Dawley rats were given access to nicotine (0.03 mg/kg) for 23 h per
      day for 20 days. On day 1 of acquisition of nicotine SA, plasma levels of both
      adrenocorticotropin and corticosterone were significantly increased 15-30 min
      after the first dose of nicotine. These hormonal changes were no longer
      significant on day 3, when adrenocorticotropin levels were <60 pg/ml and
      corticosterone levels were <110 ng/ml during the hour after the first dose of
      nicotine. Chronic nicotine SA (20 days) significantly augmented (2-3-fold) both
      hormonal responses to mild foot shock stress (0.6 mA, 0.5 s per shock, 5 shocks
      per 5 min), but did not affect hormonal responses to moderate shock (1.2 mA, 0.5
      s per shock, 5 shocks per 5 min), lipopolysaccharide or immobilization. Similar
      data were obtained in Lewis rats. These results provide further support for the
      concept that chronic nicotine SA is a stressor. In alignment with the effects of
      other stressors, nicotine activated the HPA axis on the first day of SA, but
      desensitization occurred with repeated exposure. Furthermore, chronic nicotine SA
      selectively cross-sensitized the HPA response to a novel stressor. These
      observations suggest that nicotine may selectively increase the HPA response to
      stressors in human smokers.

PMID- 17551543
TI  - Acute amphetamine exposure selectively desensitizes kappa-opioid receptors in the
      nucleus accumbens.
AB  - In the present study, we investigated the effects of psychostimulant exposure on
      kappa-opioid peptide (KOP) receptor signaling in the rat mesolimbic system. A
      single subcutaneous (s.c.) injection of amphetamine (2.5 mg/kg) reduced the KOP
      receptor-mediated inhibition of glutamate release in the nucleus accumbens shell,
      as a consequence of KOP receptor desensitization. This effect was blocked by
      dopamine (DA) receptor antagonists or the nonselective opioid antagonist,
      naltrexone (1 mg/kg, s.c.), and mimicked by the KOP receptor agonists U69593
      (0.32 mg/kg, s.c.) and dynorphin (1 microM), indicating that an amphetamine
      induced release of dynorphin is producing a long-lasting desensitization of the
      KOP receptor. Despite the fact that amphetamine also increases dynorphin release
      in the ventral tegmental area (VTA), KOP receptor function in this region was not
      affected by amphetamine; there was no difference in the KOP receptor-mediated
      change in firing rate or resting membrane potential measured in VTA neurons from
      saline- or amphetamine-treated animals. This study demonstrates that amphetamine
      can produce regionally selective adaptations in KOP receptor signaling, which
      may, in turn, alter the effects of subsequent drug exposure.

PMID- 17551544
TI  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin in maternal breast milk and newborn head
      circumference.
AB  - Dioxins are known to affect infant growth and neurodevelopment in both humans and
      animals. In this study, we examined the relationship between neonatal head
      circumference, which is related to fetal brain development, and the concentration
      of dioxins in breast milk as an indicator of maternal exposure. A total of 42
      milk samples were obtained on the fifth to eighth postpartum day from mothers in
      Japan exposed to dioxins in the environment. The levels of seven dioxins and 10
      furan isomers were measured in each milk sample using an HR-GC/MS system. The
      relationships between the concentration of each dioxin isomer and newborn size,
      including head circumference, were then investigated after adjustment for
      confounding factors. The concentration of 2,3,7,8-tetrachlorodibenzo-p-dioxin
      (TCDD), the most toxic dioxin isomer, negatively correlated with newborn head
      circumference, even after adjustment for gestational age, infant sex, parity and
      other confounding factors. However, there were no significant relationships
      between the concentration of other dioxin and furan isomers in maternal breast
      milk and infant height, weight and chest circumference at birth. These facts
      suggested that fetal brain development might be influenced by maternal exposure
      to TCDD in the environment.

PMID- 17551545
TI  - MRI-based thrombolytic therapy in acute stroke: finally, the proof of concept by
      DEFUSE.

PMID- 17551546
TI  - Are anxiety disorders undertreated in patients with multiple sclerosis?

PMID- 17551547
TI  - [Research and fantasy].

PMID- 17551548
TI  - [When the brain fails in liver failure].

PMID- 17551549
TI  - [More quickly back?].

PMID- 17551550
TI  - [Mammography screening--time for evaluation?].

PMID- 17551551
TI  - [Childhood acute lymphoblastic leukemia in Norway 1992-2000].
AB  - BACKGROUND: Acute lymphoblastic leukemia is the most common malignancy in
      childhood. The survival rate has increased steadily over the last 40 years.
      MATERIAL AND METHODS: All children aged 0-15 years and diagnosed in Norway in the
      period 1992-2000, were included in the study (n = 301). The patients were
      followed up until 1.1. 2005. RESULTS AND INTERPRETATION: The diagnosis was made
      in 301 children, 33 new cases per year (range 24 to 40) on average. The peak
      incidence was between 2 and 5 years. Four of 6 infants with acute lymphoblastic
      leukemia and all 4 with mature B-cell leukemia are alive. Two of the remaining
      291 children died before treatment was started. 289 were all treated according to
      the common Nordic NOPHO-ALL 1992 protocol. All children achieved remission
      (99.7%), except for one who died before remission was achieved. 55 children (19%)
      relapsed. Radiation to the brain as part of central nervous system prophylaxis
      was given to just 10% of the children. The 10-year event-free survival (p-EFS)
      was 76%, and 244 of 289 (84%) were alive 4-13 years after the diagnosis was made.
      The data are comparable with the best international results.

PMID- 17551552
TI  - [Thoracic injuries at a regional trauma centre].
AB  - BACKGROUND: The purpose of this study was to establish patient characteristics
      and the severity and extent of thoracic injury for patients referred to a
      Norwegian regional trauma centre. MATERIAL AND METHODS: All patients (n = 436)
      treated for thoracic injuries at St. Olavs University Hospital between 01.01.
      2003 and 31.12. 2004 were analysed retrospectively. The patients were identified
      from the hospital diagnosis registry by ICD-10 codes. RESULTS: Traffic accidents
      and falls accounted for 92% of all injuries. The most common thoracic injury was
      rib fracture (55%) and the most common internal thoracic injury was pneumothorax
      (24%). About half of the patients (221/446) had associated extra-thoracic
      injuries. Observation and pain relief was the only treatment in 290 patients.
      Chest tube was the most common treatment, and was used in 88 cases (20%). 50
      patients (12%) received ventilator treatment. Nine patients underwent thoracic
      surgery, four of these died. In-hospital mortality was 5% (20/436 patients). Head
      injury and bleeding from internal organs were the most frequent causes of death.
      CONCLUSIONS: Thoracic injuries are a frequent challenge at St. Olavs University
      Hospital. Many patients have both thoracic and extra-thoracic injuries. Mortality
      is related to the severity of the injury, advanced age and comorbidity.

PMID- 17551553
TI  - [The general practitioner's view on hormone replacement therapy during and after
      menopause].
AB  - BACKGROUND: The evidence base for hormone replacement therapy of women during and
      after menopause has been strengthened in recent years. The aim of the study was
      to investigate Norwegian GPs' attitude to hormone replacement treatment in
      menopause, their knowledge of effects and indications, the risk of side effects,
      and the personal use of hormone treatment by female GPs. MATERIAL AND METHODS: A
      questionnaire was sent to 400 Norwegian GPs, randomly drawn from the membership
      list of GPs in the Norwegian Medical Association, in May 2004. RESULTS: We
      received answers from 72%. The answers imply that most Norwegian GPs know the
      current evidence base regarding the effects and side effects of hormone
      replacement therapy. Most of them indicate that they follow the Norwegian
      recommendations about indications and contra-indications, but that they continue
      the treatment longer than recommended. A large majority of the respondents agreed
      to the statements that hormone treatment increases the risk of breast cancer,
      that it does not prevent heart infarction and that the most important reason to
      prescribe hormone treatment is bothersome hot flushes. Female GPs seem to be
      better updated on some aspects of the treatment than men. 14 out of 17 peri- and
      postmenopausal female GPs were using or had used such treatment. INTERPRETATION:
      Norwegian GPs are generally well updated regarding new evidence in this field.
      The proportion of menopausal female GPs who take hormone treatment themselves has
      remained quite stable and is substantially higher than that for the average for
      the population. This finding may imply that menopausal female GPs regard the
      risks of treatment as low, and that most of them find the benefits of treatment
      greater than the risks.

PMID- 17551554
TI  - [Patient satisfaction after hospitalisation in a psychiatric institution].
AB  - BACKGROUND: There are few studies on the relation between clinical variables and
      patient satisfaction, and the results are not consistent. MATERIAL AND METHODS:
      87 in-patients at a psychiatric unit filled in a questionnaire for personality
      pathology, PDQ-4+, on admission, and the symptom measures MADRS-S and SCL-5 on
      admission and discharge in 2003-2004. They were also interviewed about patient
      satisfaction before discharge. RESULTS: The mean scores for patient satisfaction
      were high, and patients experienced a substantial decrease in symptoms during
      their stay. There were statistically significant positive correlations between
      reductions in MADRS-S and SCL-5 and patient satisfaction. The correlations were
      strongest for MADRS-S (r = 0.59, p < 0.01). There were negative correlations
      between patient satisfaction and personality pathology. Altered depression status
      explained 43% of the variance in patient satisfaction. The PDQ-4+ total score
      explained an additional 4% of the variance, while length of stay, age and sex
      contributed minimally. INTERPRETATION: Patient satisfaction was significantly
      affected by symptom reduction and to some extent by personality pathology, while
      duration of the hospital stay and sociodemographic factors had limited influence.

PMID- 17551555
TI  - [Enforcement of the mimimum legal age for purchase of alcohol].
AB  - BACKGROUND: Little is known about the enforcement of minimum legal age for
      purchase of alcohol (18 years) in Norway. We have assessed to what extent this
      requirement is fulfilled in grocery stores, on-premise outlets and monopoly
      outlets. MATERIAL AND METHODS: Questionnaires were filled in by 13-17 year-olds
      who had started drinking. They were asked about the frequency of purchase
      attempts in grocery stores, on-premise outlets and in monopoly outlets in the
      past year and how often their attempt to buy alcohol had been refused. RESULTS:
      Slightly more than 20% of the under-aged alcohol consumers (n = 9,309) had tried
      to buy beer in grocery stores; a similar proportion had tried to buy alcohol in
      pubs, bars, etc, and less than 5% had tried monopoly outlets. More than half of
      the attempts in grocery stores, 80% in on-premise venues and two thirds of those
      in monopolies were successful (i.e. purchase was not denied). INTERPRETATION: A
      stricter enforcement of the minimum legal age is likely to reduce availability of
      alcohol to the under-aged.

PMID- 17551556
TI  - [Disturbances in ammonia metabolism in hepatic failure].
AB  - BACKGROUND: Serious hepatocellular dysfunction leads to disturbances in the
      ammonia metabolism and increases the risk for development of hepatic
      encephalopathy. The present paper describes pathophysiological patterns for
      development of hyperammonemia in patients with liver diseases and discusses the
      rationale for novel ammonia lowering strategies. MATERIAL AND METHODS: The
      present paper is based on experimental research performed in a porcine model of
      acute liver failure and a literature search in Pubmed. RESULTS: Under normal
      conditions the intestines and the kidneys are the main ammonia producing organs,
      whereas the liver and skeletal muscles are the major ammonia consuming organs.
      Small and large intestines contribute equally to the release of ammonia.
      Development of intra- and extra hepatic portasystemic shunts, impaired urea
      synthesis, and reduced hepatic perivenous glutamine synthesis capacity,
      contribute to the development of hyperammonaemia with hepatic failure. The
      kidneys are quantitatively as important as the portal drained viscera in ammonia
      production, but can adapt to hyperammonaemia by reducing the production of
      ammonia to the blood and at the same time increase its excretion in urine.
      Furthermore, the lungs are metabolically active, but their role in
      hyperammonaemia remains unsettled. Skeletal muscle contributes to reducing the
      ammonia level in the body through synthesis of glutamine from equimolar
      quantities of glutamate and ammonia. INTERPRETATION: Current therapeutic
      recommendations on protein restriction, use of antibiotics and lactulosis to
      patients with hepatic failure are not sufficiently documented. There is a need
      for development of novel ammonia lowering strategies.

PMID- 17551557
TI  - [Laparoscopic aortic surgery].
AB  - BACKGROUND: Laparoscopic aortic surgery (LAS), performed since 1993, has
      undergone a number of technical improvements during recent years. The published
      results are comparable with those for open surgery. The aim of this article is to
      present the method with a focus on technical details, and at the same time
      present our experience with this technique. MATERIAL AND METHODS: Eight patients
      with debilitating intermittent claudication were operated with a total
      laparoscopic aortofemoral bypass. Operations were performed through a
      transperitoneal retrorenal approach. Median age of the patients was 61 years
      (range 51-76). All patients had an aortoiliac occlusive disease of type D
      according to the Transatlantic Inter Society Consensus (TASC). Prior to the
      procedures an operation team followed a structured training programme that
      comprised using a training model and operating on pigs, and visited an
      international referral centre. RESULTS AND INTERPRETATION: All operations were
      successfully performed. No patient developed per- or post-operative
      complications. Median post-operative hospital stay was four days. LAS is a
      technically demanding procedure and it can be established through well targeted
      and carefully planned training.

PMID- 17551558
TI  - [Planned hospitalization after deliberate self-harm].
AB  - BACKGROUND: Deliberate self-harm appears to be a common problem, especially among
      young people. In mental health care deliberate self-harm is often associated with
      emotionally unstable patients or with personality disorders of a more serious
      nature. Our department offers planned hospitalisation during 1-2 years for
      patients who deliberately and frequently harm themselves and often use
      psychiatric services. MATERIAL AND METHODS: Chart journals for 9 patients were
      examined retrospectively for determination of long-term outcome. Rates of
      deliberate self-harm were selected into two categories, suicide attempts and self
      mutilation. The number and type of inpatient hospitalisations and inpatient days
      were used to estimate the use of psychiatric services. RESULTS AND
      INTERPRETATION: The rates of deliberate self-harm, use of psychiatric health
      services and especially use of acute psychiatric services were reduced after
      introduction of planned hospitalization. Planned hospitalisation may be useful
      for this group of patients, but the results of this study should be interpreted
      with care as they are based on a small retrospective study.

PMID- 17551559
TI  - [Health complaints related to dental filling materials].
AB  - BACKGROUND: A wide range of materials is used in dental treatment. To what extent
      these materials lead to adverse reactions is under dispute. The aim of this study
      was to investigate whether patients with suspected adverse reactions to dental
      materials experienced an improvement in health after these materials were
      replaced. MATERIAL AND METHODS: Information on health complaints related to
      dental materials was obtained from the Dental Biomaterials Adverse Reaction Unit
      in Bergen, Norway for 142 patients. A follow-up questionnaire regarding
      subjective health was sent to these patients 1(1/2) to 2(1/2) years later. A
      similar questionnaire was sent to a reference group of 800 persons drawn from the
      general population. RESULTS: The patient group had more health complaints than
      the reference group (p < 0.001) at baseline. Of the 84 patients who completed the
      questionnaire (59%) 35 had changed dental materials. Amalgam fillings had been
      replaced in most of these patients. 23 patients (66%) reported improved health
      after replacement. Intraoral complaints decreased significantly (p = 0.022), and
      were most pronounced in patients with lesions in contact with dental materials.
      The intensity of various health complaints decreased slightly in most patients
      with replaced dental materials, but the patient group still had significantly
      higher health complaint indices than the reference group. INTERPRETATION: The
      intensity of subjective health complaints was reduced after replacement of dental
      materials, but it was still higher than for a comparable group in the general
      population. The results indicate that there may be a specific health effect of
      replacing dental materials, but normal symptom fluctuations over time and placebo
      effects such as positive effects from expectations and general care from the
      health personnel may have had an influence.

PMID- 17551560
TI  - [The DRG system's interaction with medical practice].
AB  - Financing of health services is partly based on coding of diagnoses by diagnose
      related groups (DRG). Arriving at a medical diagnosis is not a straight-forward
      procedure, and it is likely that the DRG-system itself affects the medical
      diagnosis. The DRG system undermines the theoretical challenge of arriving at a
      medical diagnosis and is perceived more as a tool for supervising medical
      doctors.

PMID- 17551561
TI  - [Do medical errors occur only in Trondheim?].

PMID- 17551562
TI  - [Imprecise about biobank legislation].

PMID- 17551564
TI  - [Three statements and three questions about life-prolonging treatment].

PMID- 17551566
TI  - [Does the new St Olav Hospital want to collapse?].

PMID- 17551569
TI  - [A new, cheaper and simpler anti-malaria preparation].

PMID- 17551572
TI  - A prospective three-year cohort study of the epidemiology and virology of acute
      respiratory infections of children in rural India.
AB  - BACKGROUND: Acute respiratory infection (ARI) is a major killer of children in
      developing countries. Although the frequency of ARI is similar in both developed
      and developing countries, mortality due to ARI is 10-50 times higher in
      developing countries. Viruses are common causes of ARI among such children, yet
      the disease burden of these infections in rural communities is unknown.
      METHODOLOGY/PRINCIPAL FINDINGS: A prospective longitudinal study was carried out
      in children enrolled from two rural Indian villages at birth and followed weekly
      for the development of ARI, classified as upper respiratory infection, acute
      lower respiratory infection (ALRI), or severe ALRI. Respiratory syncytial virus
      (RSV), influenza, parainfluenza viruses and adenoviruses in nasopharyngeal
      aspirates were detected by direct fluorescent antibody testing (DFA) and, in
      addition, centrifugation enhanced culture for RSV was done. 281 infants enrolled
      in 39 months and followed until 42 months. During 440 child years of follow-up
      there were 1307 ARIs, including 236 ALRIs and 19 severe ALRIs. Virus specific
      incidence rates per 1000 child years for RSV were total ARI 234, ALRI 39, and
      severe ALRI 9; for influenza A total ARI 141, ALRI 39; for INF B total ARI 37;
      for PIV1 total ARI 23, for PIV2 total ARI 28, ALRI 5; for parainfluenza virus 3
      total ARI 229, ALRI 48, and severe ALRI 5 and for adenovirus total ARI 18, ALRI
      5. Repeat infections with RSV were seen in 18 children. CONCLUSIONS/SIGNIFICANCE:
      RSV, influenza A and parainfluenza virus 3 were important causes of ARI among
      children in rural communities in India. These data will be useful for vaccine
      design, development and implementation purposes.

PMID- 17551571
TI  - Neurotrophic factors and neural prostheses: potential clinical applications based
      upon findings in the auditory system.
AB  - Spiral ganglion neurons (SGNs) are the target cells of the cochlear implant, a
      neural prosthesis designed to provide important auditory cues to severely or
      profoundly deaf patients. The ongoing degeneration of SGNs that occurs following
      a sensorineural hearing loss is, therefore, considered a limiting factor in
      cochlear implant efficacy. We review neurobiological techniques aimed at
      preventing SGN degeneration using exogenous delivery of neurotrophic factors.
      Application of these proteins prevents SGN degeneration and can enhance neurite
      outgrowth. Furthermore, chronic electrical stimulation of SGNs increases
      neurotrophic factor-induced survival and is correlated with functional benefits.
      The application of neurotrophic factors has the potential to enhance the benefits
      that patients can derive from cochlear implants; moreover, these techniques may
      be relevant for use with neural prostheses in other neurological conditions.

PMID- 17551573
TI  - Risk factors for and clinical outcome of congenital cytomegalovirus infection in
      a peri-urban West-African birth cohort.
AB  - BACKGROUND: Congenital cytomegalovirus (CMV) infection is the most prevalent
      congenital infection worldwide. Epidemiology and clinical outcomes are known to
      vary with socio-economic background, but few data are available from developing
      countries, where the overall burden of infectious diseases is frequently high.
      METHODOLOGY/PRINCIPAL FINDINGS: As part of an ongoing birth cohort study in The
      Gambia among term infants, urine samples were collected at birth and tested by
      PCR for the presence of CMV DNA. Risk factors for transmission and clinical
      outcome were assessed, including placental malaria infection. Babies were
      followed up at home monthly for morbidity and anthropometry, and at one year of
      age a clinical evaluation was performed. The prevalence of congenital CMV
      infection was 5.4% (40/741). A higher prevalence of hepatomegaly was the only
      significant clinical difference at birth. Congenitally infected children were
      more often first born babies (adjusted odds ratio (OR) 5.3, 95% confidence
      interval (CI) 2.0-13.7), more frequently born in crowded compounds (adjusted OR
      2.9, 95%CI 1.0-8.3) and active placental malaria was more prevalent (adjusted OR
      2.9, 95%CI 1.0-8.4). These associations were corrected for maternal age, bed net
      use and season of birth. During the first year of follow up, mothers of
      congenitally infected children reported more health complaints for their child.
      CONCLUSIONS/SIGNIFICANCE: In this study, the prevalence of congenital CMV among
      healthy neonates was much higher than previously reported in industrialised
      countries, and was associated with active placental malaria infection. There were
      no obvious clinical implications during the first year of life. The effect of
      early life CMV on the developing infant in the Gambia could be mitigated by
      environmental factors, such as the high burden of other infections.

PMID- 17551574
TI  - Asymmetry of early endosome distribution in C. elegans embryos.
AB  - BACKGROUND: Endocytosis is involved in the regulation of many cellular events,
      including signalling, cell migration, and cell polarity. To begin to investigate
      roles for endocytosis in early C. elegans development, we examined the
      distribution and dynamics of early endosomes (EEs) in embryos.
      METHODOLOGY/PRINCIPAL FINDINGS: EEs are primarily found at the cell periphery
      with an initially uniform distribution after fertilization. Strikingly, we find
      that during the first cell cycle, EEA-1 positive EEs become enriched at the
      anterior cortex. In contrast, the Golgi compartment shows no asymmetry in
      distribution. Asymmetric enrichment of EEs depends on acto-myosin contractility
      and embryonic PAR polarity. In addition to their localization at the cortex, EEs
      are also found around the centrosome. These EEs move rapidly (1.3 microm/s) from
      the cortex directly to the centrosome, a speed comparable to that of the minus
      end directed motor dynein. CONCLUSIONS/SIGNIFICANCE: We speculate that the
      asymmetry of early endosomes might play a role in cell asymmetries or fate
      decisions.

PMID- 17551575
TI  - Increased levels of circulating IL-16 and apoptosis markers are related to the
      activity of Whipple's disease.
AB  - BACKGROUND: Whipple's disease (WD) is an infectious disease caused by Tropheryma
      whipplei, which replicates in macrophages and induces the release of interleukin
      (IL)-16, a substrate of caspase 3, and macrophage apoptosis. The disease is
      characterized by intestinal, cardiac or neurological manifestations; its
      diagnosis is based on invasive analysis requiring tissue biopsies or
      cerebrospinal fluid puncture. The disease progression is slow and often
      complicated by relapses despite empirical antibiotic treatment.
      METHODOLOGY/PRINCIPAL FINDINGS: We monitored circulating levels of IL-16 and
      nucleosomes in 36 French patients with WD; among them, some patients were
      enrolled in a longitudinal follow-up. As compared to control subjects, the
      circulating levels of both IL-16 and nucleosomes were increased in untreated
      patients with WD presenting as intestinal, cardiac or neurological
      manifestations. This finding was specific to WD since the circulating levels of
      IL-16 and nucleosomes were not increased in patients with unrelated inflammatory
      diseases such as inflammatory bowel disease or Q fever endocarditis. We also
      found that increased levels of IL-16 and nucleosomes were related to the activity
      of the disease. Indeed, successful antibiotic treatment decreased those levels
      down to those of control subjects. In contrast, patients who suffered from
      relapses exhibited circulating levels of IL-16 and nucleosomes as high as those
      of untreated patients. CONCLUSIONS/SIGNIFICANCE: Circulating levels of both IL-16
      and nucleosomes were increased in WD. This finding provides simple and non
      invasive tools for the diagnosis and the prognosis of WD.

PMID- 17551576
TI  - Role of C677T and A1298C MTHFR, A2756G MTR and -786 C/T eNOS gene polymorphisms
      in atrial fibrillation susceptibility.
AB  - BACKGROUND: Hyperhomocysteinemia has been suggested to play a role in the
      NonValvular Atrial Fibrillation (NVAF) pathogenesis. Polymorphisms in genes
      coding for homocysteine (Hcy) metabolism enzymes may be associated with
      hyperhomocysteinemia and NVAF. METHODOLOGIES: 456 NVAF patients and 912 matched
      controls were genotyped by an electronic microchip technology for C677T and
      A1298C MTHFR, A2756G MTR, and -786C/T eNOS gene polymorphisms. Hcy was determined
      by an immunoassay method. PRINCIPAL FINDINGS: The genotype distribution of the
      four polymorphisms as well as genotype combinations did not differ in patients
      and controls. Hcy was higher in patients than in controls (15.2, 95%CI 14.7-15.7
      vs 11.3, 95%CI 11.0-11.6 micromol/L; p<0.0001). In both populations, a genotype
      phenotype association (p<0.0001) between Hcy and C677T MTHFR polymorphism was
      observed; in controls a significant (p = 0.029) association between tHcy and 
      786C/T eNOS polymorphism was also observed. At the multivariate analysis the NVAF
      risk significantly increased in the upper quartiles of Hcy compared to the
      lowest: OR from 2.8 (1.68-4.54 95%CI) in Q2 to 12.9 (7.96-21.06 95%CI) in Q4.
      CONCLUSIONS: Our data demonstrated the four polymorphisms, although able, at
      least in part, to affect Hcy, were not associated with an increased risk of NVAF
      per se or in combination.

PMID- 17551577
TI  - Concave pit-containing scaffold surfaces improve stem cell-derived osteoblast
      performance and lead to significant bone tissue formation.
AB  - BACKGROUND: Scaffold surface features are thought to be important regulators of
      stem cell performance and endurance in tissue engineering applications, but
      details about these fundamental aspects of stem cell biology remain largely
      unclear. METHODOLOGY AND FINDINGS: In the present study, smooth clinical-grade
      lactide-coglyolic acid 85:15 (PLGA) scaffolds were carved as membranes and
      treated with NMP (N-metil-pyrrolidone) to create controlled subtractive pits or
      microcavities. Scanning electron and confocal microscopy revealed that the NMP
      treated membranes contained: (i) large microcavities of 80-120 microm in diameter
      and 40-100 microm in depth, which we termed primary; and (ii) smaller
      microcavities of 10-20 microm in diameter and 3-10 microm in depth located within
      the primary cavities, which we termed secondary. We asked whether a microcavity
      rich scaffold had distinct bone-forming capabilities compared to a smooth one. To
      do so, mesenchymal stem cells derived from human dental pulp were seeded onto the
      two types of scaffold and monitored over time for cytoarchitectural
      characteristics, differentiation status and production of important factors,
      including bone morphogenetic protein-2 (BMP-2) and vascular endothelial growth
      factor (VEGF). We found that the microcavity-rich scaffold enhanced cell
      adhesion: the cells created intimate contact with secondary microcavities and
      were polarized. These cytological responses were not seen with the smooth-surface
      scaffold. Moreover, cells on the microcavity-rich scaffold released larger
      amounts of BMP-2 and VEGF into the culture medium and expressed higher alkaline
      phosphatase activity. When this type of scaffold was transplanted into rats,
      superior bone formation was elicited compared to cells seeded on the smooth
      scaffold. CONCLUSION: In conclusion, surface microcavities appear to support a
      more vigorous osteogenic response of stem cells and should be used in the design
      of therapeutic substrates to improve bone repair and bioengineering applications
      in the future.

PMID- 17551578
TI  - The stability and formation of native proteins from unfolded monomers is
      increased through interactions with unrelated proteins.
AB  - The intracellular concentration of protein may be as high as 400 mg per ml; thus
      it seems inevitable that within the cell, numerous protein-protein contacts are
      constantly occurring. A basic biochemical principle states that the equilibrium
      of an association reaction can be shifted by ligand binding. This indicates that
      if within the cell many protein-protein interactions are indeed taking place,
      some fundamental characteristics of proteins would necessarily differ from those
      observed in traditional biochemical systems. Accordingly, we measured the effect
      of eight different proteins on the formation of homodimeric triosephosphate
      isomerase from Trypanosoma brucei (TbTIM) from guanidinium chloride unfolded
      monomers. The eight proteins at concentrations of micrograms per ml induced an
      important increase on active dimer formation. Studies on the mechanism of this
      phenomenon showed that the proteins stabilize the dimeric structure of TbTIM, and
      that this is the driving force that promotes the formation of active dimers.
      Similar data were obtained with TIM from three other species. The heat changes
      that occur when TbTIM is mixed with lysozyme were determined by isothermal
      titration calorimetry; the results provided direct evidence of the weak
      interaction between apparently unrelated proteins. The data, therefore, are
      strongly suggestive that the numerous protein-protein interactions that occur in
      the intracellular space are an additional control factor in the formation and
      stability of proteins.

PMID- 17551580
TI  - Climate change cannot explain the upsurge of tick-borne encephalitis in the
      Baltics.
AB  - BACKGROUND: Pathogens transmitted by ticks cause human disease on a greater scale
      than any other vector-borne infections in Europe, and have increased dramatically
      over the past 2-3 decades. Reliable records of tick-borne encephalitis (TBE)
      since 1970 show an especially sharp upsurge in cases in Eastern Europe coincident
      with the end of Soviet rule, including the three Baltic countries, Estonia,
      Latvia and Lithuania, where national incidence increased from 1992 to 1993 by 64,
      175 and 1,065%, respectively. At the county level within each country, however,
      the timing and degree of increase showed marked heterogeneity. Climate has also
      changed over this period, prompting an almost universal assumption of causality.
      For the first time, we analyse climate and TBE epidemiology at sufficiently fine
      spatial and temporal resolution to question this assumption.
      METHODOLOGY/PRINCIPAL FINDING: Detailed analysis of instrumental records of
      climate has revealed a significant step increase in spring-time daily maximum
      temperatures in 1989. The seasonal timing and precise level of this warming were
      indeed such as could promote the transmission of TBE virus between larval and
      nymphal ticks co-feeding on rodents. These changes in climate, however, are
      virtually uniform across the Baltic region and cannot therefore explain the
      marked spatio-temporal heterogeneity in TBE epidemiology.
      CONCLUSIONS/SIGNIFICANCE: Instead, it is proposed that climate is just one of
      many different types of factors, many arising from the socio-economic transition
      associated with the end of Soviet rule, that have acted synergistically to
      increase both the abundance of infected ticks and the exposure of humans to these
      ticks. Understanding the precise differential contribution of each factor as a
      cause of the observed epidemiological heterogeneity will help direct control
      strategies.

PMID- 17551579
TI  - Interactive domains in the molecular chaperone human alphaB crystallin modulate
      microtubule assembly and disassembly.
AB  - BACKGROUND: Small heat shock proteins regulate microtubule assembly during cell
      proliferation and in response to stress through interactions that are poorly
      understood. METHODOLOGY: Novel functions for five interactive sequences in the
      small heat shock protein and molecular chaperone, human alphaB crystallin, were
      investigated in the assembly/disassembly of microtubules and aggregation of
      tubulin using synthetic peptides and mutants of human alphaB crystallin.
      PRINCIPAL FINDINGS: The interactive sequence (113)FISREFHR(120) exposed on the
      surface of alphaB crystallin decreased microtubule assembly by approximately 45%.
      In contrast, the interactive sequences, (131)LTITSSLSSDGV(142) and
      (156)ERTIPITRE(164), corresponding to the beta8 strand and the C-terminal
      extension respectively, which are involved in complex formation, increased
      microtubule assembly by approximately 34-45%. The alphaB crystallin peptides,
      (113)FISREFHR(120) and (156)ERTIPITRE(164), inhibited microtubule disassembly by
      approximately 26-36%, and the peptides (113)FISREFHR(120) and
      (131)LTITSSLSSDGV(142) decreased the thermal aggregation of tubulin by
      approximately 42-44%. The (131)LTITSSLSSDGV(142) and (156)ERTIPITRE(164) peptides
      were more effective than the widely used anti-cancer drug, Paclitaxel, in
      modulating tubulin<-->microtubule dynamics. Mutagenesis of these interactive
      sequences in wt human alphaB crystallin confirmed the effects of the alphaB
      crystallin peptides on microtubule assembly/disassembly and tubulin aggregation.
      The regulation of microtubule assembly by alphaB crystallin varied over a narrow
      range of concentrations. The assembly of microtubules was maximal at alphaB
      crystallin to tubulin molar ratios between 1:4 and 2:1, while molar ratios >2:1
      inhibited microtubule assembly. CONCLUSIONS AND SIGNIFICANCE: Interactive
      sequences on the surface of human alphaB crystallin collectively modulate
      microtubule assembly through a dynamic subunit exchange mechanism that depends on
      the concentration and ratio of alphaB crystallin to tubulin. These are the first
      experimental results in support of the functional importance of the dynamic
      subunit model of small heat shock proteins.

PMID- 17551581
TI  - The information coded in the yeast response elements accounts for most of the
      topological properties of its transcriptional regulation network.
AB  - The regulation of gene expression in a cell relies to a major extent on
      transcription factors, proteins which recognize and bind the DNA at specific
      binding sites (response elements) within promoter regions associated with each
      gene. We present an information theoretic approach to modeling transcriptional
      regulatory networks, in terms of a simple "sequence-matching" rule and the
      statistics of the occurrence of binding sequences of given specificity in random
      promoter regions. The crucial biological input is the distribution of the amount
      of information coded in these cognate response elements and the length
      distribution of the promoter regions. We provide an analysis of the
      transcriptional regulatory network of yeast Saccharomyces cerevisiae, which we
      extract from the available databases, with respect to the degree distributions,
      clustering coefficient, degree correlations, rich-club coefficient and the k-core
      structure. We find that these topological features are in remarkable agreement
      with those predicted by our model, on the basis of the amount of information
      coded in the interaction between the transcription factors and response elements.

PMID- 17551582
TI  - Transmission parameters of the 2001 foot and mouth epidemic in Great Britain.
AB  - Despite intensive ongoing research, key aspects of the spatial-temporal evolution
      of the 2001 foot and mouth disease (FMD) epidemic in Great Britain (GB) remain
      unexplained. Here we develop a Markov Chain Monte Carlo (MCMC) method for
      estimating epidemiological parameters of the 2001 outbreak for a range of simple
      transmission models. We make the simplifying assumption that infectious farms
      were completely observed in 2001, equivalent to assuming that farms that were
      proactively culled but not diagnosed with FMD were not infectious, even if some
      were infected. We estimate how transmission parameters varied through time,
      highlighting the impact of the control measures on the progression of the
      epidemic. We demonstrate statistically significant evidence for assortative
      contact patterns between animals of the same species. Predictive risk maps of the
      transmission potential in different geographic areas of GB are presented for the
      fitted models.

PMID- 17551583
TI  - HIV-specific probabilistic models of protein evolution.
AB  - Comparative sequence analyses, including such fundamental bioinformatics
      techniques as similarity searching, sequence alignment and phylogenetic
      inference, have become a mainstay for researchers studying type 1 Human
      Immunodeficiency Virus (HIV-1) genome structure and evolution. Implicit in
      comparative analyses is an underlying model of evolution, and the chosen model
      can significantly affect the results. In general, evolutionary models describe
      the probabilities of replacing one amino acid character with another over a
      period of time. Most widely used evolutionary models for protein sequences have
      been derived from curated alignments of hundreds of proteins, usually based on
      mammalian genomes. It is unclear to what extent these empirical models are
      generalizable to a very different organism, such as HIV-1-the most extensively
      sequenced organism in existence. We developed a maximum likelihood model fitting
      procedure to a collection of HIV-1 alignments sampled from different viral genes,
      and inferred two empirical substitution models, suitable for describing between
      and within-host evolution. Our procedure pools the information from multiple
      sequence alignments, and provided software implementation can be run efficiently
      in parallel on a computer cluster. We describe how the inferred substitution
      models can be used to generate scoring matrices suitable for alignment and
      similarity searches. Our models had a consistently superior fit relative to the
      best existing models and to parameter-rich data-driven models when benchmarked on
      independent HIV-1 alignments, demonstrating evolutionary biases in amino-acid
      substitution that are unique to HIV, and that are not captured by the existing
      models. The scoring matrices derived from the models showed a marked difference
      from common amino-acid scoring matrices. The use of an appropriate evolutionary
      model recovered a known viral transmission history, whereas a poorly chosen model
      introduced phylogenetic error. We argue that our model derivation procedure is
      immediately applicable to other organisms with extensive sequence data available,
      such as Hepatitis C and Influenza A viruses.

PMID- 17551584
TI  - Identification of potential therapeutic drugs for huntington's disease using
      Caenorhabditis elegans.
AB  - BACKGROUND: The prolonged time course of Huntington's disease (HD)
      neurodegeneration increases both the time and cost of testing potential
      therapeutic compounds in mammalian models. An alternative is to initially assess
      the efficacy of compounds in invertebrate models, reducing time of testing from
      months to days. METHODOLOGY/PRINCIPAL FINDINGS: We screened candidate therapeutic
      compounds that were identified previously in cell culture/animal studies in a C.
      elegans HD model and found that two FDA approved drugs, lithium chloride and
      mithramycin, independently and in combination suppressed HD neurotoxicity. Aging
      is a critical contributor to late onset neurodegenerative diseases. Using a
      genetic strategy and a novel assay, we demonstrate that lithium chloride and
      mithramycin remain neuroprotective independent of activity of the forkhead
      transcription factor DAF-16, which mediates the effects of the insulin-like
      signaling pathway on aging. CONCLUSIONS/SIGNIFICANCE: These results suggest that
      pathways involved in polyglutamine-induced degeneration are distinct from
      specific aging pathways. The assays presented here will be useful for rapid and
      inexpensive testing of other potential HD drugs and elucidating pathways of drug
      action. Additionally, the neuroprotection conferred by lithium chloride and
      mithramycin suggests that these drugs may be useful for polyglutamine disease
      therapy.

PMID- 17551585
TI  - Quantifying exocytosis by combination of membrane capacitance measurements and
      total internal reflection fluorescence microscopy in chromaffin cells.
AB  - Total internal reflection fluorescence microscopy (TIRF-Microscopy) allows the
      observation of individual secretory vesicles in real-time during exocytosis. In
      contrast to electrophysiological methods, such as membrane capacitance recording
      or carbon fiber amperometry, TIRF-Microscopy also enables the observation of
      vesicles as they reside close to the plasma membrane prior to fusion. However,
      TIRF-Microscopy is limited to the visualization of vesicles that are located near
      the membrane attached to the glass coverslip on which the cell grows. This has
      raised concerns as to whether exocytosis measured with TIRF-Microscopy is
      comparable to global secretion of the cell measured with membrane capacitance
      recording. Here we address this concern by combining TIRF-Microscopy and membrane
      capacitance recording to quantify exocytosis from adrenal chromaffin cells. We
      found that secretion measured with TIRF-Microscopy is representative of the
      overall secretion of the cells, thereby validating for the first time the TIRF
      method as a measure of secretion. Furthermore, the combination of these two
      techniques provides a new tool for investigating the molecular mechanism of
      synaptic transmission with combined electrophysiological and imaging techniques.

PMID- 17551586
TI  - A post-synaptic scaffold at the origin of the animal kingdom.
AB  - BACKGROUND: The evolution of complex sub-cellular structures such as the synapse
      requires the assembly of multiple proteins, each conferring added functionality
      to the integrated structure. Tracking the early evolution of synapses has not
      been possible without genomic information from the earliest branching animals. As
      the closest extant relatives to the Eumetazoa, Porifera (sponges) represent a
      pivotal group for understanding the evolution of nervous systems, because sponges
      lack neurons with clearly recognizable synapses, in contrast to eumetazoan
      animals. METHODOLOGY/PRINCIPAL FINDINGS: We show that the genome of the
      demosponge Amphimedon queenslandica possesses a nearly complete set of post
      synaptic protein homologs whose conserved interaction motifs suggest assembly
      into a complex structure. In the critical synaptic scaffold gene, dlg, residues
      that make hydrogen bonds and van der Waals interactions with the PDZ ligand are
      100% conserved between sponge and human, as is the motif organization of the
      scaffolds. Expression in Amphimedon of multiple post-synaptic gene homologs in
      larval flask cells further supports the existence of an assembled structure.
      Among the few post-synaptic genes absent from Amphimedon, but present in
      Eumetazoa, are receptor genes including the entire ionotropic glutamate receptor
      family. CONCLUSIONS/SIGNIFICANCE: Highly conserved protein interaction motifs and
      co-expression in sponges of multiple proteins whose homologs interact in
      eumetazoan synapses indicate that a complex protein scaffold was present at the
      origin of animals, perhaps predating nervous systems. A relatively small number
      of crucial innovations to this pre-existing structure may represent the founding
      changes that led to a post-synaptic element.

PMID- 17551587
TI  - HIV-associated TB in An Giang Province, Vietnam, 2001-2004: epidemiology and TB
      treatment outcomes.
AB  - BACKGROUND: Mortality is high in HIV-infected TB patients, but few studies from
      Southeast Asia have documented the benefits of interventions, such as co
      trimoxazole (CTX), in reducing mortality during TB treatment. To help guide
      policy in Vietnam, we studied the epidemiology of HIV-associated TB in one
      province and examined factors associated with outcomes, including the impact of
      CTX use. METHODOLOGY/PRINCIPAL FINDINGS: We retrospectively abstracted data for
      all HIV-infected persons diagnosed with TB from 2001-2004 in An Giang, a province
      in southern Vietnam in which TB patients receive HIV counseling and testing. We
      used standard WHO definitions to classify TB treatment outcomes. We conducted
      multivariate analysis to identify risk factors for the composite outcome of
      death, default, or treatment failure during TB treatment. From 2001-2004, 637 HIV
      infected TB patients were diagnosed in An Giang. Of these, 501 (79%) were male,
      321 (50%) were aged 25-34 years, and the most common self-reported HIV risk
      factor was sex with a commercial sex worker in 221 (35%). TB was classified as
      smear-positive in 531 (83%). During TB treatment, 167 (26%) patients died, 9 (1%)
      defaulted, and 6 (1%) failed treatment. Of 454 patients who took CTX, 116 (26%)
      had an unsuccessful outcome compared with 33 (70%) of 47 patients who did not
      take CTX (relative risk, 0.4; 95% confidence interval [CI], 0.3-0.5). Adjusting
      for male sex, rural residence, TB smear status and disease location, and the
      occurrence of adverse events during TB treatment in multivariate analysis, the
      benefit of CTX persisted (adjusted odds ratio for unsuccessful outcome 0.1; CI,
      0.1-0.3). CONCLUSIONS/SIGNIFICANCE: In An Giang, Vietnam, HIV-associated TB was
      associated with poor TB treatment outcomes. Outcomes were significantly better in
      those taking CTX. This finding suggests that Vietnam should consider applying WHO
      recommendations to prescribe CTX to all HIV-infected TB patients.

PMID- 17551588
TI  - A two-locus global DNA barcode for land plants: the coding rbcL gene complements
      the non-coding trnH-psbA spacer region.
AB  - BACKGROUND: A useful DNA barcode requires sufficient sequence variation to
      distinguish between species and ease of application across a broad range of taxa.
      Discovery of a DNA barcode for land plants has been limited by intrinsically
      lower rates of sequence evolution in plant genomes than that observed in animals.
      This low rate has complicated the trade-off in finding a locus that is universal
      and readily sequenced and has sufficiently high sequence divergence at the
      species-level. METHODOLOGY/PRINCIPAL FINDINGS: Here, a global plant DNA barcode
      system is evaluated by comparing universal application and degree of sequence
      divergence for nine putative barcode loci, including coding and non-coding
      regions, singly and in pairs across a phylogenetically diverse set of 48 genera
      (two species per genus). No single locus could discriminate among species in a
      pair in more than 79% of genera, whereas discrimination increased to nearly 88%
      when the non-coding trnH-psbA spacer was paired with one of three coding loci,
      including rbcL. In silico trials were conducted in which DNA sequences from
      GenBank were used to further evaluate the discriminatory power of a subset of
      these loci. These trials supported the earlier observation that trnH-psbA coupled
      with rbcL can correctly identify and discriminate among related species.
      CONCLUSIONS/SIGNIFICANCE: A combination of the non-coding trnH-psbA spacer region
      and a portion of the coding rbcL gene is recommended as a two-locus global land
      plant barcode that provides the necessary universality and species
      discrimination.

PMID- 17551589
TI  - The making of a queen: TOR pathway is a key player in diphenic caste development.
AB  - BACKGROUND: Honey bees (Apis mellifera) provide a principal example of diphenic
      development. Excess feeding of female larvae results in queens (large
      reproductives). Moderate diet yields workers (small helpers). The signaling
      pathway that links provisioning to female developmental fate is not understood,
      yet we reasoned that it could include TOR (target of rapamycin), a nutrient- and
      energy-sensing kinase that controls organismal growth. METHODOLOGY/PRINCIPAL
      FINDINGS: Here, the role of Apis mellifera TOR (amTOR) in caste determination is
      examined by rapamycin/FK506 pharmacology and RNA interference (RNAi) gene
      knockdown. We show that in queen-destined larvae, the TOR inhibitor rapamycin
      induces the development of worker characters that are blocked by the antagonist
      FK506. Further, queen fate is associated with elevated activity of the Apis
      mellifera TOR encoding gene, amTOR, and amTOR gene knockdown blocks queen fate
      and results in individuals with worker morphology. CONCLUSIONS/SIGNIFICANCE: A
      much-studied insect dimorphism, thereby, can be governed by the TOR pathway. Our
      results present the first evidence for a role of TOR in diphenic development, and
      suggest that adoption of this ancestral nutrient-sensing cascade is one
      evolutionary pathway for morphological caste differentiation in social insects.

PMID- 17551590
TI  - Molecular dynamics of retinoic acid-induced craniofacial malformations:
      implications for the origin of gnathostome jaws.
AB  - BACKGROUND: Intake of retinoic acid (RA) or of its precursor, vitamin A, during
      early pregnancy is associated with increased incidence of craniofacial lesions.
      The origin of these teratogenic effects remains enigmatic as in cranial neural
      crest cells (CNCCs), which largely contribute to craniofacial structures, the RA
      transduction pathway is not active. Recent results suggest that RA could act on
      the endoderm of the first pharyngeal arch (1stPA), through a RARbeta-dependent
      mechanism. METHODOLOGY/PRINCIPAL FINDINGS: Here we show that RA provokes
      dramatically different craniofacial malformations when administered at slightly
      different developmental times within a narrow temporal interval corresponding to
      the colonization of the 1(st) PA by CNCCs. We provide evidence showing that RA
      acts on the signalling epithelium of the 1(st) PA, gradually reducing the
      expression of endothelin-1 and Fgf8. These two molecular signals are instrumental
      in activating Dlx genes in incoming CNCCs, thereby triggering the morphogenetic
      programs, which specify different jaw elements. CONCLUSIONS/SIGNIFICANCE: The
      anatomical series induced by RA-treatments at different developmental times
      parallels, at least in some instances, the supposed origin of modern jaws (e.g.,
      the fate of the incus). Our results might provide a conceptual framework for the
      rise of jaw morphotypes characteristic of gnathostomes.

PMID- 17551591
TI  - Phagocytosis of cholesteryl ester is amplified in diabetic mouse macrophages and
      is largely mediated by CD36 and SR-A.
AB  - Type 2 diabetes (T2D) is associated with accelerated atherosclerosis, which
      accounts for approximately 75% of all diabetes-related deaths. Here we
      investigate the link between diabetes and macrophage cholesteryl ester
      accumulation. When diabetic (db/db) mice are given cholesteryl ester
      intraperitoneally (IP), peritoneal macrophages (PerMPhis) recovered from these
      animals showed a 58% increase in intracellular cholesteryl ester accumulation
      over PerMPhis from heterozygote control (db/+) mice. Notably, PerMPhi fluid-phase
      endocytosis and large particle phagocytosis was equivalent in db/+and db/db mice.
      However, IP administration of CD36 and SR-A blocking antibodies led to 37% and
      25% reductions in cholesteryl ester accumulation in PerMPhi. Finally, in order to
      determine if these scavenger receptors (SRs) were part of the mechanism
      responsible for the increased accumulation of cholesteryl esters observed in the
      diabetic mouse macrophages, receptor expression was quantified by flow cytometry.
      Importantly, db/db PerMPhis showed a 43% increase in CD36 expression and an 80%
      increase in SR-A expression. Taken together, these data indicate that direct
      cholesteryl ester accumulation in mouse macrophages is mediated by CD36 and SR-A,
      and the magnitude of accumulation is increased in db/db macrophages due to
      increased scavenger receptor expression.

PMID- 17551592
TI  - Pathogen proteins eliciting antibodies do not share epitopes with host proteins:
      a bioinformatics approach.
AB  - The best way to prevent diseases caused by pathogens is by the use of vaccines.
      The advent of genomics enables genome-wide searches of new vaccine candidates,
      called reverse vaccinology. The most common strategy to apply reverse vaccinology
      is by designing subunit recombinant vaccines, which usually generate an humoral
      immune response due to B-cell epitopes in proteins. A major problem for this
      strategy is the identification of protective immunogenic proteins from the
      surfome of the pathogen. Epitope mimicry may lead to auto-immune phenomena
      related to several human diseases. A sequence-based computational analysis has
      been carried out applying the BLASTP algorithm. Therefore, two huge databases
      have been created, one with the most complete and current linear B-cell epitopes,
      and the other one with the surface-protein sequences of the main human
      respiratory bacterial pathogens. We found that none of the 7353 linear B-cell
      epitopes analysed shares any sequence identity region with human proteins capable
      of generating antibodies, and that only 1% of the 2175 exposed proteins analysed
      contain a stretch of shared sequence with the human proteome. These findings
      suggest the existence of a mechanism to avoid autoimmunity. We also propose a
      strategy for corroborating or warning about the viability of a protein linear B
      cell epitope as a putative vaccine candidate in a reverse vaccinology study; so,
      epitopes without any sequence identity with human proteins should be very good
      vaccine candidates, and the other way around.

PMID- 17551593
TI  - The role of the substantia nigra pars compacta in regulating sleep patterns in
      rats.
AB  - BACKGROUND: As of late, dopaminergic neurotransmission has been recognized to be
      involved in the generation of sleep disturbances. Increasing evidence shows that
      sleep disturbances in Parkinson's disease (PD) patients are mostly related to the
      disease itself, rather than being a secondary phenomenon. Evidence contained in
      the literature lends support to the hypothesis that the dopaminergic
      nigrostriatal pathway is closely involved in the regulation of sleep patterns.
      METHODOLOGY/PRINCIPAL FINDINGS: To test this hypothesis we examined the
      electrophysiological activity along the sleep-wake cycle of rats submitted to a
      surgically induced lesion of the SNpc by 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine (MPTP). We demonstrated that a 50% lesion of the substantia
      nigra pars compacta (SNpc) suffices to produce disruptions of several parameters
      in the sleep-wake pattern of rats. A robust and constant decrease in the latency
      to the onset of slow wave sleep (SWS) was detected throughout the five days of
      recording in both light [F((22.16)) = 72.46, p<0.0001] and dark [F((22.16)) =
      75.0, p<0.0001] periods. Also found was a pronounced increase in the percentage
      of sleep efficiency during the first four days of recording [F((21.15)) = 21.48,
      p<0.0001], in comparison to the sham group. Additionally, the reduction in the
      SNpc dopaminergic neurons provoked an ablation in the percentage of rapid eye
      movement sleep (REM) during three days of the sleep-wake recording period with a
      strong correlation (r = 0.91; p<0.0001) between the number of dopaminergic
      neurons lost and the percentage decrease of REM sleep on the first day of
      recording. On day 4, the percentage of REM sleep during the light and dark
      periods was increased, [F((22.16)) = 2.46, p<0.0007], a phenomenon consistent
      with REM rebound. CONCLUSIONS/SIGNIFICANCE: We propose that dopaminergic neurons
      present in the SNpc possess a fundamental function in the regulation of sleep
      processes, particularly in promoting REM sleep.

PMID- 17551595
TI  - Diagnostic value of peripheral lymph node biopsy in sarcoidosis: a report of 67
      cases.
AB  - A peripheral lymph node (PLN) 1 cm or greater was found in 79 of 546 sarcoidosis
      patients (14.5%) between 1972 and 2005. Seventy-two of the 79 sarcoidosis
      patients had a lymph node biopsy performed. Sixty-seven of these biopsy specimens
      were histologically diagnosed as sarcoidosis, whereas five patients had a
      reactive adenopathy. For patients with histological diagnosis of sarcoidosis,
      localizations of the biopsies were as follows: cervical (n=21), supraclavicular
      (n=20), inguinal (n=11), axillary (n=8), epitrochlear (n=5) and submandibular
      (n=2). At the time of biopsy, 12 patients had stage 0 disease, 37 patients had
      stage I disease, 14 patients had stage II disease and four patients had stage III
      disease. Skin involvement (16.4%) was the most frequently observed type of organ
      involvement in patients who had enlarged PLNs due to sarcoidosis. In the presence
      of an enlarged PLN in sarcoidosis, biopsy had a greater diagnostic value compared
      with other methods, as well as having a relatively low cost (approximately
      US$120) in Turkey. No procedure-related complications were observed. In
      conclusion, it is recommended that PLNs be thoroughly examined when sarcoidosis
      is suspected. If an enlarged PLN is found, biopsy should be routinely performed
      because it is an easy, convenient and practical method, with a low complication
      risk and a high sensitivity.

PMID- 17551594
TI  - Symposium on obesity and asthma - November 2, 2006.
AB  - Asthma and obesity are frequently associated, and obesity has been considered a
      factor contributing to both an increase in severity of asthma and to its
      development. The present document summarizes the proceedings of a symposium held
      in Montreal, Quebec, on November 2, 2006, under the auspices of the Reseau en
      sante respiratoire du Fonds de la recherche en sante du Quebec in collaboration
      with the McGill University - Strauss Severe Asthma Program, Universite Laval
      (Quebec City) and Universite de Montreal. It includes an overview of the various
      aspects of the relationships between asthma and obesity with regard to animal
      models; genetic, hormonal and physiological determinants; influence of
      comorbidities (eg, sleep apnea syndrome); epidemiology; clinical and
      psychological features; and management of asthma in the obese population.

PMID- 17551596
TI  - Admission is not always necessary for patients with community-acquired pneumonia
      in risk classes IV and V diagnosed in the emergency room.
AB  - OBJECTIVE: To determine the factors that allow patients with community-acquired
      pneumonia who are at high risk of mortality (risk classes IV and V) to be treated
      at home. DESIGN: A prospective, observational study. SETTING: Six hospitals and
      one free-standing emergency room in Edmonton, Alberta. PARTICIPANTS: The present
      study included 2354 patients in risk classes IV and V who had a diagnosis of
      pneumonia made by an emergency room physician or an internist. MEASUREMENTS:
      Symptoms, signs and laboratory findings, as well as outcome measures of length of
      stay and mortality. RESULTS: Of the total study group, 319 of the patients
      (13.5%) were treated on an ambulatory basis. Factors predictive of admission were
      definite or possible pneumonia on chest radiograph as read by a radiologist,
      functional impairment, altered mental status, substance abuse, psychiatric
      disorder, abnormal white blood cell count, abnormal lymphocyte count, oxygen
      saturation less than 90% and antibiotic administration in the week before
      admission. If chest pain was present, admission was less likely. Only two of the
      319 patients required subsequent admission (both had positive blood cultures) and
      only two died. CONCLUSIONS: A substantial number of patients in risk classes IV
      and V can be safely treated at home. Factors that help clinicians to select this
      subset of patients are discussed.

PMID- 17551597
TI  - The link between obesity and asthma: a Canadian perspective.
AB  - Asthma is considered to be more prevalent in obese subjects, and a possible
      causal link between these two entities has been suggested. In the present study,
      various observations on this relationship were reviewed, and an analysis of data
      obtained from the 2000 to 2001 Canadian Community Health Survey on the prevalence
      of self-reported asthma, medication use and allergy, according to body weight,
      was reported. Asthma medication use and self-reported asthma were more prevalent
      in the obese population, particularly in women. Mean body mass index was higher
      in the asthmatic population compared with the nonasthmatic population. Self
      reported nonfood-related allergies were higher in the more obese subjects in the
      general population, but the prevalence of allergy was not different in obese
      asthmatic subjects compared with nonobese asthmatic subjects. Smoking did not
      seem to influence the relationship between asthma and body mass index. Further
      research should investigate the mechanisms by which obesity may influence the
      prevalence of asthma or asthma-like symptoms.

PMID- 17551598
TI  - Airflow obstruction in young adults in Canada.
AB  - OBJECTIVE: Airflow obstruction is relatively uncommon in young adults, and may
      indicate potential for the development of progressive disease. The objective of
      the present study was to enumerate and characterize airflow obstruction in a
      random sample of Canadians aged 20 to 44 years. SETTING: The sample (n=2962) was
      drawn from six Canadian sites. DESIGN: A prevalence study using the European
      Community Respiratory Health Survey protocol was conducted. Airflow obstruction
      was assessed by spirometry. Bronchial responsiveness, skin reactivity to
      allergens and total serum immunoglobulin E were also measured. Logistic
      regression was used for analysis. RESULTS: Airflow obstruction was observed in
      6.4% of the sample, not associated with sex or age. The risk of airflow
      obstruction increased in patients who had smoked and in patients who had lung
      trouble during childhood. Adjusted for smoking, the risk of airflow obstruction
      was elevated for subjects with past and current asthma, skin reactivity to
      allergens, elevated levels of total immunoglobulin E and bronchial hyper
      responsiveness. Of the subjects with airflow obstruction, 21% were smokers with a
      history of asthma, 50% were smokers without asthma, 12% were nonsmokers with
      asthma and 17% were nonsmokers with no history of asthma. Bronchial hyper
      responsiveness increased the prevalence of airflow obstruction in each of these
      groups. CONCLUSION: Smoking and asthma, jointly and individually, are major
      determinants of obstructive disorders in young adults. Bronchial hyper
      responsiveness contributes to obstruction in both groups.

PMID- 17551599
TI  - The paradox of adult asthma control: "who's in control anyway?".
AB  - Surveys of Canadian patients with asthma and their physicians consistently report
      satisfaction with asthma management; however, when objective indicators are used,
      these same surveys also observe very poor levels of asthma control. The reasons
      for this apparent discrepancy, with an emphasis on the factors influencing
      adherence to therapy, are explored in the present review. Clues to the
      identification of patients at risk of dying from asthma and an approach to
      difficult asthma are discussed.

PMID- 17551600
TI  - Complete disappearance of lung abnormalities on high-resolution computed
      tomography: a case of histiocytosis X.
AB  - A case of pulmonary Langerhans cell histiocytosis, proved by both lung high
      resolution computed tomography and lung biopsy, is described. Following smoking
      cessation, lung nodules and cysts gradually disappeared on serial computed
      tomography scans, with complete clearance of the lesions after 12 months. The
      role of tobacco smoking is discussed, in detail, against the background of the
      literature.

PMID- 17551601
TI  - Thomas Spencer Wells, Bt FRCS (1818-97) and his contributions to naval medicine.
AB  - Sir Thomas Spencer Wells (1818-97) is best remembered both as a gynaecological
      surgeon, who introduced ovariectomy, and as the one who introduced the surgical
      forceps named after him. Far less is known of his career in the Royal Navy (RN)
      as an assistant surgeon and then a surgeon, and his contributions to naval
      medicine. Wells enlisted for the RN at the age of 23 years and for most of his
      naval career (1841-56) he served at the Naval Hospital, Malta (1841-48). However,
      from 1851 to 1853 he was surgeon and sanitary officer on the sloop, HMS Modeste.
      Most of Wells' contributions to the health of sailors were of a preventive
      nature, especially involving ventilation, in RN ships. He was also an enthusiast
      for quarantine and vaccination.

PMID- 17551602
TI  - Petit's screw tourniquet.

PMID- 17551603
TI  - Augusto Pellegrini (1877-1958): contributions to surgery and prosthetic
      orthopaedics.
AB  - Augusto Pellegrini worked as a general surgeon in Northern Italy. In 1905, in the
      field of orthopaedics, he described post-traumatic knee ossification, associated
      particularly with sports activities, which took the name of Pellegrini disease.
      In collaboration with Giuliano Vanghetti, he contributed to the application of
      kinematic prostheses of the upper extremity (kineplasty), enabling the patient to
      use his muscles to power the prosthesis. His surgical innovations were
      particularly in the field of abdominal surgery, at a time when antibiotics were
      not available and when radiological diagnostics were in their infancy. He
      advocated the surgical treatment of acute appendicitis 'at presentation', namely
      within 24-48 h of diagnosis, thereby reducing the development of abdominal
      complications. In 1904 he introduced disinfection of the hands solely with
      alcohol before each surgical operation, encouraging the healing of wounds by
      first intention.

PMID- 17551604
TI  - Sir George Ballingall (1786-1855): Regius Professor of Military Surgery in the
      University of Edinburgh.
AB  - George Ballingall qualified with the Licentiate Diploma of the Royal College of
      Surgeons of Edinburgh in December 1805 and joined the Army Medical Department in
      May of the following year, spending the majority of his army career in India. He
      also served in Java. Eventually, he was awarded his MD Edinburgh degree in 1819,
      and the FRCS Edinburgh and Fellowship of the Royal Society of Edinburgh during
      the following year. He was appointed to the Regius Chair of Military Surgery in
      the University of Edinburgh in November 1822, succeeding John Thomson, its first
      holder, and he held this post until his death in December 1855. Ballingall was
      the first to describe 'Madura Foot', sometimes called 'Ballingall's disease.' In
      1833, he published Outlines of Military Surgery, which ran to five editions. He
      was appointed Surgeon-Extraordinary to the King (William IV) and Surgeon to the
      Queen. He also established a fine Museum Collection to complement his Lecture
      Course. Throughout his teaching career, he campaigned vigorously in support of
      military medical educational reform. One of his sons and several grandchildren
      also served in the medical service of the army or in that of the Honourable East
      India Company.

PMID- 17551605
TI  - Thomas Prosser (c1780-1827): army surgeon on the convict ship Maria.
AB  - Between 1793 and 1815, The French Wars between Britain and France provided work
      for a generation of army surgeons. Military efficiency in record keeping and
      subsequent governmental archiving ensured that material is available for the
      biographers of such men. However, by contrast information on these surgeons while
      in civilian practice is scant. Thomas Prosser is a typical example of a well
      qualified early 19th century surgeon who chose a career with the army and who,
      while on half pay, was surgeon to a female convict ship.

PMID- 17551606
TI  - Arthur William Douthwaite (1848-99), Order of the Double Dragon, MD (USA) FRGS:
      evangelist, medical missionary, explorer.
AB  - Dr Douthwaite AW was first and foremost an evangelist. He became a doctor in
      order that he would be able better to follow his vocation of seeking to convert
      the people of China to Christianity. After an unhappy childhood and misspent
      youth, Douthwaite was converted to Christianity and went to China as a medical
      missionary. His only qualification was four years as an apothecary's apprentice
      and a short attachment at the London Hospital but he soon earned a high
      reputation as a healer and evangelist. During his first furlough, Douthwaite went
      to America and gained a full medical qualification. On his return to China, he
      was sent to Chefoo where he oversaw the development of a major mission station,
      which included one of the first medical schools for native students. His
      premature death from dysentery at the age of 51 prevented him from achieving even
      greater things.

PMID- 17551607
TI  - Leslie A (Epstein) Falk (1915-2004) and penicillin production at Oxford.
AB  - To establish penicillin as a unique chemotherapeutic agent, Howard Florey and his
      colleagues at the Sir William Dunn School of Pathology at Oxford University
      needed to produce it in significant amounts. The first attempts to grow
      Penicillium notatum for penicillin production were carried out by Florey's
      colleague, Ernst Chain, in association with an American Rhodes Scholar, Leslie A
      Epstein, beginning in 1939. Little has been known about this work except that
      some impure penicillin was obtained and shown to be non-toxic in mice. Epstein,
      who later changed his name to Falk, died in 2004 at the age of 89 years. In an
      extensive memoir covering his career, he has provided new information about this
      early work. An apparatus was constructed for large-scale growth of
      microorganisms, including P. notatum, on solid agar medium.

PMID- 17551608
TI  - Andreas Vesalius (1514-84).

PMID- 17551609
TI  - Eponymous, anonymous: Queen Anne's sign and the misnaming of a symptom.
AB  - Tracing the historical origins of an eponymous medical sign can be fraught with
      dilemmas, particularly when the evidence for the naming comes from portraiture.
      Laterally truncated eyebrows, a sign of hypothyroidism, came to be associated
      with Anne of Denmark (1574-1619), James I's Queen Consort, likely because a
      contemporaneous portrait of her by Paul van Somer shows a woman with fair and
      abbreviated brows. Extant medical information on Anne, however, does not support
      a diagnosis of hypothyroidism, nor does her very active queenship point to such
      an affliction. Nonetheless, some authorities continue to employ the label,
      invoking Queen Anne's painted likeness as proof that she was goitrous and
      manifested the characteristically shortened eyebrows of those with a deficiency
      of thyroid activity.

PMID- 17551610
TI  - Robert Seymour Bridges (1844-1930).

PMID- 17551611
TI  - Dr Jacob Mackiewicz (1887-1966) and his sign.
AB  - Dr Jacob Mackiewicz, a Jewish-Polish neurologist, described the cruralis
      phenomenon related to injury of the femoral nerve or of the fourth lumbar root.
      In 1912, only one year after graduation maxima cum laude from Moscow University,
      the 25-year-old Dr Jacob Mackiewicz described the cruralis phenomenon, regarded
      in the German and Slavic medical literature as the Mackiewicz sign: 'the patient
      lies prone, the examiner lifts the thigh in one hand, with the other hand, bends
      the patient's knee slowly; this manoeuvre causes severe pain in the anterior part
      of the thigh and over the groin. This manoeuvre indicates a femoral nerve
      injury'.

PMID- 17551612
TI  - Abraham Lincoln's Gettysburg illness.
AB  - When Abraham Lincoln delivered the Gettysburg Address, he was weak and dizzy; his
      face had a ghastly colour. That evening on the train to Washington, DC, he was
      febrile and weak, and suffered severe headaches. The symptoms continued; back
      pains developed. On the fourth day of the illness, a widespread scarlet rash
      appeared that soon became vesicular. By the tenth day, the lesions itched and
      peeled. The illness lasted three weeks. The final diagnosis, a touch of
      varioloid, was an old name for smallpox that was later used in the 20th century
      to denote mild smallpox in a partially immune individual. It was unclear whether
      Lincoln had been immunized against smallpox. Indeed, this review suggests that
      Lincoln had unmodified smallpox and that Lincoln's physicians tried to reassure
      the public that Lincoln was not seriously ill. Indeed, the successful conclusion
      of the Civil War and reunification of the country were dependent upon Lincoln's
      presidency.

PMID- 17551613
TI  - Rudolph Weigl (1883-1957)--a scientist in Poland in wartime plus ratio quam vis.
AB  - Rudolph Weigl gained a high estimation for his spectacular invention of the first
      efficient vaccine against typhus fever. Although born a German native speaker, he
      changed into a great Pole with Polish education and upbringing in a patriotic
      atmosphere. His scientific career developed in the Universities of Lvov, Cracow
      and Poznan. For him, academic employment was a constant exploration of practical
      truths and a response to human needs, and this remained a deep obligation during
      his lifetime. His vaccine saved millions, particularly during World War II.
      Despite many nominations, he was never awarded the Nobel Prize.

PMID- 17551614
TI  - Neuropathology in Germany during World War II: Julius Hallervorden (1882-1965)
      and the Nazi programme of 'euthanasia'.
AB  - In Germany, during World War II, more than 120,000 handicapped children and
      adults were murdered for the convenience of the State. To gain scientific
      knowledge, the brains of many of these patients were examined by German
      neuropathologists. Some 698 of these specimens were examined in the Kaiser
      Wilhelm-Institut fur Hirnforschung in Berlin-Buch by Julius Hallervorden, whose
      career is reviewed together with that of his superior, Hugo Spatz. Hallervorden
      also oversaw the examination of cases of mental handicap by W-J Eiche at a
      laboratory at the Hospital Brandenburg-Gorden. Also in Berlin was Berthold
      Ostertag, neuropathologist at the Rudolf-Virchow-Hospital, who examined cases
      from the Children's Ward at Wiesengrund. Smaller but significant numbers of
      brains were examined in Munich, Heidelberg, Hamburg and Schleswig. Some brains of
      similar origin were examined in Vienna and in Lubliniecz. Jurgen Peiffer has
      estimated that German neuropathologists examined 2097 brains arising from the
      Nazi Programme of 'Euthanasia'.

PMID- 17551615
TI  - Quantum chemical insights in energy dissipation and carotenoid radical cation
      formation in light harvesting complexes.
AB  - Light harvesting complexes (LHCs) have been identified in all photosynthetic
      organisms. To understand their function in light harvesting and energy
      dissipation, detailed knowledge about possible excitation energy transfer (EET)
      and electron transfer (ET) processes in these pigment proteins is of prime
      importance. This again requires the study of electronically excited states of the
      involved pigment molecules, in LHCs of chlorophylls and carotenoids. This paper
      represents a critical review of recent quantum chemical calculations on EET and
      ET processes between pigment pairs relevant for the major LHCs of green plants
      (LHC-II) and of purple bacteria (LH2). The theoretical methodology for a
      meaningful investigation of such processes is described in detail, and benefits
      and limitations of standard methods are discussed. The current status of excited
      state calculations on chlorophylls and carotenoids is outlined. It is focused on
      the possibility of EET and ET in the context of chlorophyll fluorescence
      quenching in LHC-II and carotenoid radical cation formation in LH2. In the
      context of non-photochemical quenching of green plants, it is shown that
      replacement of the carotenoid violaxanthin by zeaxanthin in its binding pocket of
      LHC-II can not result in efficient quenching. In LH2, our computational results
      give strong evidence that the S(1) states of the carotenoids are involved in
      carotenoid cation formation. By comparison of theoretical findings with recent
      experimental data, a general mechanism for carotenoid radical cation formation is
      suggested.

PMID- 17551616
TI  - A well-tempered density functional theory of electrons in molecules.
AB  - This Invited Article reports extensions of a recently developed approach to
      density functional theory with correct long-range behavior (R. Baer and D.
      Neuhauser, Phys. Rev. Lett., 2005, 94, 043002). The central quantities are a
      splitting functional gamma[n] and a complementary exchange-correlation functional
      E[n]. We give a practical method for determining the value of gamma in molecules,
      assuming an approximation for E is given. The resulting theory shows good ability
      to reproduce the ionization potentials for various molecules. However it is not
      of sufficient accuracy for forming a satisfactory framework for studying
      molecular properties. A somewhat different approach is then adopted, which
      depends on a density-independent gamma and an additional parameter w eliminating
      part of the local exchange functional. The values of these two parameters are
      obtained by best-fitting to experimental atomization energies and bond lengths of
      the molecules in the G2(1) database. The optimized values are gamma = 0.5 a and w
      = 0.1. We then examine the performance of this slightly semi-empirical functional
      for a variety of molecular properties, comparing to related works and experiment.
      We show that this approach can be used for describing in a satisfactory manner a
      broad range of molecular properties, be they static or dynamic. Most satisfactory
      is the ability to describe valence, Rydberg and inter-molecular charge-transfer
      excitations.

PMID- 17551617
TI  - Vibrational structure theory: new vibrational wave function methods for
      calculation of anharmonic vibrational energies and vibrational contributions to
      molecular properties.
AB  - A number of recently developed theoretical methods for the calculation of
      vibrational energies and wave functions are reviewed. Methods for constructing
      the appropriate quantum mechanical Hamilton operator are briefly described before
      reviewing a particular branch of theoretical methods for solving the nuclear
      Schrodinger equation. The main focus is on wave function methods using the
      vibrational self-consistent field (VSCF) as starting point, and includes
      vibrational configuration interaction (VCI), vibrational Moller-Plesset (VMP)
      theory, and vibrational coupled cluster (VCC) theory. The convergence of the
      different methods towards the full vibrational configuration interaction (FVCI)
      result is discussed. Finally, newly developed vibrational response methods for
      calculation of vibrational contributions to properties, energies, and transition
      probabilities are discussed.

PMID- 17551618
TI  - A London-type formula for the dispersion interactions of endohedral A@B systems.
AB  - A London-type formula is derived for endohedral systems. It involves the static
      dipole polarisability, alpha(1)(A) of the inner system, A, and a new type of
      dipole polarisability, alpha(-2)(B) with an r(-2) radial operator, for the outer
      system, B. The new formula has no explicit dependence on the radius, R, of B. The
      predicted interaction energies are compared against MP2 supermolecular
      calculations for A@C(60), A = He-Xe, Zn, Cd, Hg, and CH(4).

PMID- 17551619
TI  - Perturbation of water structure due to monovalent ions in solution.
AB  - The ion induced modification to the tetrahedral structure of water is a topic of
      much current interest. We address this question by interpreting neutron
      diffraction data from monovalent ionic solutions of NaCl and KCl using a computer
      assisted structural modeling technique. We investigate the effect that these ions
      have on the water-water O-O, O-H and H-H radial distribution functions as a
      function of ionic concentration. It is found that the O-H and H-H functions are
      only marginally affected by ionic composition, signaling that hydrogen bonding
      between water molecules remains largely intact, even at the highest
      concentrations. On the other hand the O-O functions are strongly modified by the
      ions. In particular the position of the second peak in g(OO)(r), is found to move
      inwards with increasing salt concentration, in a manner closely analogous to what
      happens in pure water under pressure. Furthermore by recalculating g(OO)(r) after
      excluding all the water molecules in the first hydration shell of each ion, we
      show that this structural perturbation exists outside the first hydration shell
      of the ions.

PMID- 17551620
TI  - Molecular orientational and dipolar correlation in the liquid crystal mixture E7:
      a molecular dynamics simulation study at a fully atomistic level.
AB  - Molecular dynamics simulations are reported for the four component nematic liquid
      crystal mixture E7, which is used commercially. We are able to show the growth of
      a nematic phase directly from an isotropic liquid over a 100 ns period for an all
      atom model, and study orientational and dipole order within the nematic phase.
      The simulations show that the cyanoterphenyl component of the mixture, 5CT, is
      more ordered than the three cyanobiphenyl components. The simulations show also
      that both parallel and anti-parallel dipole correlation take place in E7 but that
      the strong anti-parallel dipole correlation is localised to particular
      arrangements of molecules. It is possible to identify two key preferred
      configurations for molecular pairs in the fluid, which explain the form of the
      dipole correlation function, g(1)(r).

PMID- 17551621
TI  - Can "microwave effects" be explained by enhanced diffusion?
AB  - The "microwave effect" or non-thermal effects due to microwaves have been the
      subject of intense debate. This paper explores the following hypothesis: if the
      transport of an active species is a rate limiting step in a reaction, and if
      microwaves enhance the diffusion of that species, then the overall reaction rate
      would change under microwave heating compared with conventional heating. If the
      hypothesis is correct then it should be possible to pick those reactions that
      would speed up, slow down or stay the same, under microwave irradiation. One
      consequence of the hypothesis is that the equilibrium states (end point of the
      reactions) remain unchanged by microwave irradiation. The measurements and theory
      presented here strongly suggest that this hypothesis is correct.

PMID- 17551622
TI  - Energy selective excision of CN- following electron attachment to
      hexafluoroacetone azine ((CF3)2C=N-N=C(CF3)2).
AB  - Low energy electron attachment (DEA) to hexafluoroacetone azine (HFAA) leads to a
      remarkable energy selective excision of CN(-) within a pronounced resonance
      located at 1.35 eV. The underlying dissociative electron attachment (DEA)
      reaction involves multiple bond cleavages and rearrangement within the neutral
      products. A series of further fragment ions (F(-), CF(3)(-), (CF(3))(2)C(-) and
      (CF(3))(2)CN(-)) are observed from resonant features above 2 eV and only
      (CF(3))(2)CN(-) is additionally formed within a narrow resonance below 1 eV. In
      contrast to CN(-) all the remaining fragment ions can be formed by simple bond
      cleavages with (CF(3))(2)CN(-) being the result of a symmetric decomposition of
      the target molecule by cleavage of the (N-N) bond with the excess charge
      localised on either of the identical fragments. Our ab initio calculations
      predict an adiabatic electron affinity of HFAA close to 2 eV with the geometry of
      the relaxed anion considerably distorted with respect to that of the neutral
      molecule.

PMID- 17551623
TI  - Secondary organic aerosol from limona ketone: insights into terpene ozonolysis
      via synthesis of key intermediates.
AB  - Limona ketone was synthesized to explore the secondary organic aerosol (SOA)
      formation mechanism from limonene ozonolysis and also to test group-additivity
      concepts describing the volatility distribution of ozonolysis products from
      similar precursors. Limona ketone SOA production is indistinguishable from alpha
      pinene, confirming the expected similarity. However, limona ketone SOA production
      is significantly less intense than limonene SOA production. The very low vapor
      pressure of limonene ozonolysis products is consistent with full oxidation of
      both double bonds in limonene and furthermore with production of products other
      than ketones after oxidation of the exo double bond in limonene. Mass-balance
      constraints confirm that ketone products from exo double-bond ozonolysis have a
      minimal contribution to the ultimate product yield. These results serve as the
      foundation for an emerging framework to describe the effect on volatility of
      successive generations of organic compounds in the atmosphere.

PMID- 17551624
TI  - Two-photon absorption of Zn(II) octupolar molecules.
AB  - In this work we present an investigation of the non-linear optical (NLO)
      properties of two octupolar chromophores: [Zn(4,4'-bis(dibutylaminostyryl)-[2,2']
      bipyridine)(3)](2+) and [Zn(4,4'-bis((E)-2-(N-(TEG)pyrrol-2-yl)vinyl)-[2,2']
      bipyridine)(3)](2+) with Zn(ii) as the coordination center, using two-photon
      emission technique (TPE) in fs-pulse temporal regime. Compared to the free
      ligands, our results do not show a net increase in the two-photon absorption
      (TPA) cross-section for the octupolar complexes, once normalized to the ligand
      unit. This is in partial disagreement with a previous theoretical study
      investigating the first molecule where a significant increase of the TPA cross
      section was predicted (X. J. Liu, et al., J. Chem. Phys., 2004, 120, 11 493).

PMID- 17551625
TI  - Statistics of single molecule SERS signals: is there a Poisson distribution of
      intensities?
AB  - This paper is aimed at clarifying the statistics of single molecule (SM) surface
      enhanced Raman scattering (SERS) signals. The argument of the possible existence
      of a Poisson distribution in the statistics of intensities in SM-SERS has been
      used many times in the last decade as a proof of single molecule detection. We
      show theoretically and experimentally that the conditions under which a Poisson
      distribution would be present are so unlikely to exist in a real system that
      there is no other option but to attribute the claims to poor statistical
      sampling. We believe the argument based on Poisson statistics should be dropped
      as a proof of single molecule detection in SERS.

PMID- 17551626
TI  - Reactions of sulfur dioxide on calcium carbonate single crystal and particle
      surfaces at the adsorbed water carbonate interface.
AB  - Sulfur dioxide reactions with calcium carbonate interfaces at 296 K in the
      presence and absence of adsorbed water result in the formation of adsorbed
      sulfite and sulfate. The extent of reaction is significantly enhanced,
      approximately five- to ten-fold for particulate and single crystal CaCO(3)
      (calcite), respectively, in the presence of adsorbed water between 30 and 85% RH.
      Atomic force microscopy following the reaction shows that adsorbed water
      facilitates surface reactivity by enhancing the mobility of surface ions, giving
      rise to the formation of nanometer sized product crystallites approximately 1 nm
      in height. Simultaneous with the formation of these crystallites is pitting and
      etching of the underlying substrate, which occurs preferentially in the vicinity
      of monoatomic surface steps. In the absence of water, there is little pitting and
      no evidence for the formation of crystallites. X-Ray photoelectron core and
      valence band spectra confirm the presence of two sulfur adsorbed species, SO and
      SO, with nearly equal amounts of SO and SO in the absence of adsorbed water and
      approximately five times more SO relative to SO in the presence of adsorbed
      water. From these data, it is proposed that the nanometer-sized crystallites are
      composed primarily of CaSO(3).

PMID- 17551627
TI  - Gold as intermolecular glue: a theoretical study of nanostrips based on quinoline
      type monomers.
AB  - A family of infinite nanostrips is computationally predicted. In it monomers of
      single, double or triple aromatic rings are linked to each other by strong C-Au
      C, C-Au <-- N or N --> Au <-- N bonds. Depending on the geometry of the system
      and saturation of the bonds, these 1-D nanostrips are found to be insulators,
      narrow- or zero-gap semiconductors, or metals. The calculated dimerization and
      polymerization energies suggest clear exothermicity of formation. Varying the
      nitrogen content in the aromatic ring is found to little affect the geometry, and
      the 1-D band structure of the strips can be interpreted in a rigid-band picture.
      The orbital character of the states at the Fermi level has been analyzed. One of
      the new structures is found to be closely similar to graphene with respect to its
      band structure properties.

PMID- 17551628
TI  - N2 emission in NO and N2O reduction on Rh(100) and Rh(110).
AB  - The angular distribution of desorbing N(2) was studied in both the thermal
      decomposition of N(2)O(a) on Rh(100) at 60-140 K and the steady-state NO (or
      N(2)O) + D(2) reaction on Rh(100) and Rh(110) at 280-900 K. In the former, N(2)
      desorption shows two peaks at around 85 and 110 K. At low N(2)O coverage, the
      desorption at 85 K collimates at about 66 degrees off normal towards the [001]
      direction, whereas at high coverage, it sharply collimates along the surface
      normal. In the NO reduction on Rh(100), the N(2) desorption preferentially
      collimates at around 71 degrees off normal towards the [001] direction below
      about 700 K, whereas it collimates predominantly along the surface normal at
      higher temperatures. At lower temperatures, the surface nitrogen removal in the
      NO reduction is due to the process of NO(a) + N(a) --> N(2)O(a) --> N(2)(g) +
      O(a). On the other hand, in the steady-state N(2)O + D(2) reaction on Rh(110),
      the N(2) desorption collimates closely along the [001] direction (close to the
      surface parallel) below 340 K and shifts to ca. 65 degrees off normal at higher
      temperatures. In the reduction with CO, the N(2) desorption collimates along
      around 65 degrees off normal towards the [001] direction above 520 K, and shifts
      to 45 degrees at 445 K with decreasing surface temperature. It is proposed that
      N(2)O is oriented along the [001] direction on both surfaces before dissociation
      and the emitted N(2) is not scattered by adsorbed hydrogen.

PMID- 17551629
TI  - Pilicides-small molecules targeting bacterial virulence.
AB  - In a time of emerging bacterial resistance there is a vital need for new targets
      and strategies in antibacterial therapy. Using uropathogenic Escherichia coli as
      a model pathogen we have developed a class of compounds, pilicides, which inhibit
      the formation of virulence-associated organelles termed pili. The pilicides
      interfere with a highly conserved bacterial assembly and secretion system called
      the chaperone-usher pathway, which is abundant in a vast number of Gram-negative
      pathogens and serves to assemble multi-protein surface fibers (pili/fimbriae).
      This class of compounds provides a platform to gain insight into important
      biological processes such as the molecular mechanisms of the chaperone-usher
      pathway and the sophisticated function of pili. Pili are primarily involved in
      bacterial adhesion, invasion and persistence to host defenses. On this basis,
      pilicides can aid the development of new antibacterial agents.

PMID- 17551630
TI  - Designed evolution of artificial metalloenzymes: protein catalysts made to order.
AB  - Artificial metalloenzymes based on biotin-streptavidin technology, a "fusion" of
      chemistry and biology, illustrate how asymmetric catalysts can be improved and
      evolved using chemogenetic approaches.

PMID- 17551631
TI  - Oligodeoxynucleotides incorporating structurally simple 5-alkynyl-2'
      deoxyuridines fluorometrically respond to hybridization.
AB  - Selected 5-ethynyl derivatives of 2'-deoxyuridine are shown to fluorometrically
      respond to hybridization and selectively base-pair to adenine whilst maintaining
      duplex stability.

PMID- 17551632
TI  - An efficient method for the synthesis of enol ethers and enecarbamates. Total
      syntheses of isoindolobenzazepine alkaloids, lennoxamine and chilenine.
AB  - An efficient method for the synthesis of enol ethers and enecarbamates has been
      developed based on catalytic hydrosilane reduction of alpha-phosphonoxy enol
      ethers and alpha-phosphonoxy enecarbamates. This method has been applied to the
      total syntheses of two isoindolobenzazepine alkaloids, lennoxamine and chilenine.

PMID- 17551633
TI  - A highly efficient cycloaddition of vinylarenes with electron-deficient alkynes
      affording 1,2-disubstituted-3,4-dihydronaphthalenes catalysed by N,N
      dimethylformamide dimethyl acetal.
AB  - 1,2-Disubstituted-3,4-dihydronaphthalenes could be conveniently synthesized with
      high yields by the cycloaddition reactions of easily available vinylarenes with
      electron-deficient alkynes such as dimethyl, or diethyl acetylenedicarboxylate,
      methyl phenylpropiolate in the presence of DMF.DMA (N,N-dimethylformamide
      dimethyl acetal) as organocatalyst.

PMID- 17551634
TI  - Oligonucleotides forming an i-motif: the pH-dependent assembly of individual
      strands and branched structures containing 2'-deoxy-5-propynylcytidine.
AB  - Non-branched and branched oligonucleotides incorporating consecutive runs of 2'
      deoxy-5-propynylcytidine residues () instead of 2'-deoxycytidine () were
      synthesized. For this, phosphoramidite building blocks of 2'-deoxy-5
      propynylcytidine () were prepared using acetyl, benzoyl or N,N-di-n
      butylaminomethylidene protecting groups. The formation of the i-motif assemblies
      incorporating 2'-deoxy-5-propynylcytidine residues was confirmed by temperature
      dependent CD- and UV-spectra as well as by ion-exchange chromatography. The low
      pK(a)-value of nucleoside (pK(a) = 3.3) compared to dC (pK(a) = 4.5) required
      strong acidic conditions for i-motif formation. Branched oligonucleotide residues
      with strands in a parallel orientation lead to a strong stabilization of the i
      motif allowing aggregation even at non-optimal pH conditions (pH = 5). The
      immobilization of oligonucleotides incorporating multiple residues of on 15 nm
      gold nanoparticles generated DNA-gold nanoparticle conjugates which are able to
      aggregate into i-motif structures at pH 5.

PMID- 17551635
TI  - Structure elucidation of C80, C81 and C82 isoprenoid tetraacids responsible for
      naphthenate deposition in crude oil production.
AB  - A series of C(80) isoprenoid 20-bis-16,16'-biphytanyl tetraacids has previously
      been found to be responsible for calcium naphthenate scaling in crude oil
      processing. This paper describes the structure elucidation by high-field NMR
      spectroscopy of the structures of the series of homologous C(80) tetraacids
      containing 4-8 five-membered rings. In addition, the structures of methyl
      substituted C(81) and C(82) analogues containing 7 and 8 five-membered rings have
      been determined for the first time. The biosynthetic implications are discussed.

PMID- 17551636
TI  - Rapid mass spectrometric identification of human genomic polymorphisms using
      multiplexed photocleavable mass-tagged probes and solid phase capture.
AB  - A mass spectrometric approach for rapid and simultaneous detection of several
      single nucleotide polymorphisms (SNPs) is reported. Oligonucleotide single base
      extension (SBE) primers, labelled at the 5'-end with photocleavable, quaternised
      and brominated peptidic mass tags, are extended by a mixture of the four
      dideoxynucleotides of which one is biotinylated. The 3'-biotinylated extension
      products are captured by streptavidin-coated solid phase magnetic beads, whilst
      non-biotinylated extension products and unreacted primers are washed away.
      Quaternised and brominated mass tags, cleaved from captured extension products
      during analysis by matrix-assisted laser desorption/ionisation-time-of-flight
      (MALDI-TOF) MS, are detected at pmol levels. This method is applied to the
      analysis of mitochondrial DNA polymorphisms for the purpose of human
      identification.

PMID- 17551637
TI  - Water-soluble carbosilane dendrimers protect phosphorothioate oligonucleotides
      from binding to serum proteins.
AB  - Treatment of dendriplexes formed between water-soluble carbosilane dendrimers and
      phosphorothioate oligodeoxynucleotides (ODN) with the anionic detergent sodium
      dodecyl sulfate disrupted the complexes indicating that the nature of the union
      in such dendriplexes is merely electrostatic. However, dendriplexes were not
      dissociated by serum proteins like bovine or human serum albumins, as assessed by
      gel electrophoresis and fluorescence experiments. This would imply a dendrimer
      mediated protective effect able to prevent ODN interactions with serum proteins
      and additionally could translate into a reduction of the ODN doses needed to
      achieve the biological effects. The employment of carbosilane dendrimers as
      carriers may solve the problem of ODN kidnapping by plasmatic proteins as a key
      drawback for therapeutics involving ODNs. As examples, transfection processes on
      normal primary peripheral blood cells and diagnosis of HIV infection in the
      presence of serum have been assayed.

PMID- 17551638
TI  - Anion recognition and anion-mediated self-assembly with thiourea-functionalised
      fused [3]polynorbornyl frameworks.
AB  - Three conformationally preorganised host molecules based on the [3]polynorbornyl
      framework and incorporating di-urea receptors were synthesised and their
      interaction with a series of anions investigated by (1)H NMR spectroscopy. A high
      affinity of each host molecule for dihydrogenphosphate (H(2)PO(4)(-)) and
      dihydrogenpyrophosphate (H(2)P(2)O(7)(2-)) was identified. In addition to binding
      to the urea receptors of the host molecules, evidence for an interaction
      involving the non-polar C-H groups within the binding cavity of the framework and
      guest anions was also discovered. Furthermore, an unusual 2 : 1 host-to-anion
      stoichiometry was indicated when binding H(2)P(2)O(7)(2-), and a model for the
      anion-mediated self-assembly of this complex species is proposed.

PMID- 17551639
TI  - Sialic acid and N-acyl sialic acid analog production by fermentation of
      metabolically and genetically engineered Escherichia coli.
AB  - Sialic acid is the terminal sugar found on most glycoproteins and is crucial in
      determining serum half-life and immunogenicity of glycoproteins. Sialic acid
      analogs are antiviral therapeutics as well as crucial tools in bacterial
      pathogenesis research, immunobiology and development of cancer diagnostic
      imaging. The scarce supply of sialic acid hinders production of these materials.
      We have developed an efficient, rapid and cost effective fermentation route to
      access sialic acid. Our approach uses low cost feedstock, produces an
      industrially relevant amount of sialic acid and is scalable to manufacturing
      levels. We have also shown that precursor directed biosynthesis can be used to
      produce a N-acyl sialic acid analog. This work demonstrates the feasibility of
      engineering manufacturing-friendly bacteria to produce complex, unavailable small
      molecules.

PMID- 17551640
TI  - Inclusion complexes of cyclodextrins with biradicals linked by a polyether chain-
      an EPR study.
AB  - Complexation of beta-cyclodextrin with flexible nitroxide biradicals linked by a
      polyethylene glycol chain was monitored by EPR spectroscopy. The EPR spectra of
      the uncomplexed biradicals show an exchange interaction due to the flexibility of
      the polyethylene glycol chain. Complexation with cyclodextrin leads to the
      disappearance of the exchange interaction in the EPR spectra. The complexation
      can be reversed by the addition of competing guests (e.g., adamantane
      derivatives). At high concentration, the inclusion complexes precipitate, and
      differential scanning calorimetry (DSC) of the precipitates proved the formation
      of complexes. Elemental analysis data revealed that the complexes contain several
      cyclodextrin units per biradical but that the composition was not stoichiometric.

PMID- 17551641
TI  - Design and synthesis of all diastereomers of cyclic pseudo-dipeptides as mimics
      of cyclic CXCR4 pentapeptide antagonists.
AB  - The four diastereomers of 2,5-bis[(3-guanidino)propyl]-1-[3-(4
      hydroxyphenyl)propionyl]-7-(2-naphthylacetyl)-1,4,7-triazacycloundec-9-en-3-one (
      ) and of 2,5-bis[(3-guanidino)propyl]-1-(4-hydroxyphenylacetyl)-7-(2
      naphthylacetyl)-1,4,7-triazacycloundec-9-en-3-one (-) were synthesized by a
      divergent methodology from l- and D-glutamic acids. The 11-membered ring core was
      made by ring closing metathesis of linear bis(allylamines), and the guanidyl
      functions were introduced by a simultaneous double Mitsunobu reaction using
      bis(Boc)guanidine. These compounds were designed to mimic cyclic pentapeptide
      FC131 (c[Gly-D-Tyr-Arg-Arg-Nal]).

PMID- 17551642
TI  - Synthetic studies towards garsubellin A: synthesis of model systems and potential
      mimics by regioselective lithiation of bicyclo[3.3.1]nonane-2,4,9-trione
      derivatives from catechinic acid.
AB  - Bridgehead lithiations have successfully been carried out on substrates derived
      from catechinic acid, which possess the core bicyclo[3.3.1]nonane-1,3,5-trione
      structure present in garsubellin A. Using an external quench method, various
      electrophiles have been incorporated at the C-5 bridgehead position in a one-step
      process that appears to be sensitive to the substitution pattern on the bicyclic
      system. Regioselective lithiation at the C-3 sp(2) centre was achieved by
      changing the base used from LDA to LTMP. Following the introduction of a prenyl
      substituent by bridgehead substitution, annulation of a THF ring, analogous to
      that in garsubellin A, was possible via an epoxidation-ring opening sequence.
      Oxidative modification of the catechol substituent of the catechinic acid core
      was possible to give systems with muconic acid, ortho-quinone or furan 2
      carboxylic acid side chains.

PMID- 17551643
TI  - Oxaaza cyclophanes in the recognition of nucleotides. The role of oxygen and
      electron-rich aromatic rings.
AB  - Dioxapolyaza cyclophanes derived from resorcinol and different polyamine chains
      have been studied in aqueous solution as abiotic receptors for nucleotides. The
      presence of the additional ethyleneoxy subunits is reflected in a higher basicity
      and in a significant increase in the log K values for the interaction with
      nucleotides relative to that of related polyazacyclophanes.

PMID- 17551644
TI  - Pyrene aromatic arrays on RNA duplexes as helical templates.
AB  - RNA oligomers having multiple (2 to 4) pyrenylmethyl substituents at the 2'-O
      sugar residues were synthesized. UV-melting studies showed that the pyrene
      modified RNAs could form duplexes with complementary RNA sequences without loss
      of thermal stability. Absorption, fluorescence, and circular dichroism (CD)
      spectra revealed that the incorporated pyrenes projected toward the outside of A
      form RNA duplexes and assembled in helical aromatic arrays along the minor
      grooves of the RNA duplexes. Results of computer simulations agreed with the
      assembled structures of the pyrenes. The helical pyrene arrays exhibited
      remarkably strong excimer fluorescence, which was dependent on the sequence
      contexts of RNA duplexes.

PMID- 17551645
TI  - Joining the rings: the preparation of 2- and 3-indenyl-triptycenes, and curious
      related processes.
AB  - The indenyltriptycenes, and , where the 3- or 2-indenyl, respectively, is
      attached at the 9-position of the triptycene, are attractive prototypes of
      molecular gearing systems that can also incorporate a brake. These molecules have
      been prepared from their respective indenylanthracenes, and , by the [4 + 2]
      cycloaddition of benzyne to the anthracene fragment, and the rotational barriers
      about the indenyl-triptycenyl single bonds in (12 kcal mol(-1)) and (<9 kcal mol(
      1)) have been measured. The precursor anthracenes, and , were prepared by using
      palladium-catalysed coupling reactions. Unexpectedly, the Heck-type reaction of 9
      bromoanthracene, , with indene leads to the formation of 3-indenylanthracene ;
      moreover, this process is accompanied by a novel palladium-catalysed
      carbocyclisation reaction leading to the indenophenanthrylene . The addition of
      benzyne to 9-(3-indenyl)anthracene, , yields the corresponding indenyltriptycene,
      , and, surprisingly, the anthracenyl methano-bridged phenanthrene . It has been
      demonstrated that 2-arylindenes can act as 1,3-dienes in the [4 + 2]
      cycloadditions of benzyne. The products , , and have been characterised by X-ray
      crystallography.

PMID- 17551646
TI  - Asymmetric synthesis of 3,4-anti- and 3,4-syn-substituted aminopyrrolidines via
      lithium amide conjugate addition.
AB  - The diastereoselective conjugate addition of homochiral lithium amides to methyl
      4-(N-allyl-N-benzylamino)but-2-enoate has been used as the key step in a simple
      and efficient protocol for the preparation of 3,4-substituted aminopyrrolidines.
      This protocol provides a complementary and stereoselective route to both anti-
      and syn-3-amino-4-alkylpyrrolidines as well as anti- and syn-3-hydroxy-4
      aminopyrrolidines, in high de and ee viabeta-amino enolate functionalisation.
      This methodology has been applied to the synthesis of anti-(3S,4S)- and syn
      (3R,4S)-3-methoxy-4-(N-methylamino)pyrrolidine.

PMID- 17551647
TI  - Isothiocyanato-calix[4]phyrin-(1,1,1,1): a useful intermediate for the synthesis
      of derivatised anion sensors.
AB  - A calix[4]phyrin-(1,1,1,1) substituted with a 4-isothiocyanatophenyl group has
      been synthesised and used to attach the macrocycle to a solid support. The NCS
      group can also be used to further functionalise the calix[4]phyrin-(1,1,1,1) by
      reaction with amines and amino acids. Stability constants for anion binding by
      the calix[4]phyrin-(1,1,1,1) are reported and these show a clear ability to
      differentiate F(-) and HSO(4)(-) from Cl(-), Br(-), I(-) which can be detected by
      both NMR and UV-visible spectroscopy.

PMID- 17551648
TI  - Hydroaminations of unactivated alkenes with basic alkylamines: group 4 metal
      halide catalysts and Bronsted-acid organocatalysts.
AB  - Two distinct economical catalysts for intramolecular hydroaminations of
      electronically unactivated alkenes with basic amines are described, which are
      based on (a) group 4 metal halides under basic reaction conditions or (b)
      Bronsted-acid organocatalysts.

PMID- 17551649
TI  - Highly selective synthesis of oxabicycloalkanes by indium tribromide-mediated
      cyclization reactions of epoxyalkenes.
AB  - The cyclization of epoxyalkenes to oxabicycloalkanes is catalyzed by
      stoichiometric quantities of indium tribromide which exhibits excellent
      selectivity giving the oxabicyclic product in high yield in preference to other
      cyclized or rearrangement products.

PMID- 17551650
TI  - Retinopathy of prematurity in Brazil: an emerging problem.

PMID- 17551651
TI  - RIX4414 (Rotarix): a live attenuated human rotavirus vaccine.

PMID- 17551652
TI  - Gastroesophageal reflux and chronic respiratory disease: past, present, and
      future.

PMID- 17551653
TI  - Nasopharyngeal pH and gastroesophageal reflux in children with chronic
      respiratory disease.
AB  - OBJECTIVES: The aim of this case-control study was to evaluate the nasopharyngeal
      pH (NasopH) in children with normal or abnormal pH-metry in two groups of
      patients; 1) children presenting gastroenterological symptoms; and 2) children
      with chronic respiratory symptoms. METHODS: From February 2004 to January 2005,
      all consecutive patients referred for 24-hour pH-metry and in whom
      gastroesophageal reflux disease was suspected were enrolled in a prospective
      study. They were assigned to four groups: gastroenterological symptoms with
      normal (A) or abnormal (B) pH-metries (GG), and chronic respiratory symptoms with
      normal (C) or abnormal (D) pH-metries (RG). NasopH was measured for 5 minutes,
      before the 24-hour test was performed. RESULTS: Thirty-eight pH-metry tests were
      included (20 in the RG and 18 in the GG). Abnormal pH-metry results were observed
      in 11 patients in the GG and in 12 in the RG. NasopH means were 6.3273 and
      5.6917, respectively (p<0.0001). Average nasopharyngeal pH was 5.6917 among the
      12 RG patients with abnormal pH-metry results and 6.5000 among the remaining
      eight patients with normal test results (p=0.0006). Analysis of the RG with a
      receiver operating characteristic (ROC) curve showed pH of 5.8 as cutoff point
      (sensitivity of 91.7% and specificity of 87.5%). The area below the ROC curve was
      0.870. CONCLUSIONS: Nasopharyngeal pH is significantly lower among patients in
      the RG presenting abnormal pH-metry results. A 5.8 NasopH has good sensitivity
      and specificity and can be used as a screening test in patients with chronic
      respiratory diseases to select those for whom conventional 24-hour pH-metry is
      indicated.

PMID- 17551654
TI  - Chronic interstitial lung disease in children.
AB  - OBJECTIVES: To describe clinical and diagnostic features and the results of
      therapeutic conduct in a group of pediatric patients with chronic interstitial
      lung disease. METHODS: A retrospective study of 25 immunocompetent patients, aged
      2 months to 17 years, with chronic interstitial lung disease, admitted to the
      Pediatric Pulmonary Section, Department of Pediatrics, Hospital dos Servidores do
      Estado, over a 20-year period (1984-2004). A routine protocol for persistent
      chronic pneumonias was used and the patients with interstitial lung disease were
      selected. Clinical, laboratory and imaging data were analyzed. RESULTS: Twenty
      five patients were diagnosed with chronic interstitial lung disease, 13 were aged
      less than 2 years and 17 were male. Diagnoses were made based on history,
      physical examination and routine tests in one case, based on more complex tests
      in three cases and based on the results of invasive tests in 21 cases (20 by lung
      biopsy and one by bronchoalveolar lavage). Except for one patient with pulmonary
      lymphangiectasia, the long-term treatment (1 to 7 years) consisted of
      corticosteroid, in six cases associated with hydroxychloroquine. Four patients
      required home oxygen therapy. The authors followed the patients in the outpatient
      department (6 a 8 visits/year). Patient outcome was: good (15); regular, with
      mild sequelae (4); and poor, with severe sequelae (3). One patient was lost in
      the follow-up period and two died. CONCLUSIONS: Chronic interstitial lung
      diseases in children are a group of rare pulmonary disorders, but a relevant one
      because of the possible progression to pulmonary fibrosis. Early diagnosis and a
      long-term, specialized treatment and follow-up are important for the patient
      outcome. Pediatricians should be aware of these diseases because in many cases
      diagnosis and treatment are overlooked.

PMID- 17551655
TI  - Biochemical assessment of vitamin A in schoolchildren from a rural community.
AB  - OBJECTIVE: To investigate the prevalence of vitamin A deficiency among
      schoolchildren from a rural area in the Distrito Federal, Brazil, and to
      correlate this with rates of anemia and malnutrition. METHODS: From a total of
      179 students, the study recruited 155 schoolchildren (5 to 18 years), whose
      parents gave permission for blood tests. Plasma retinol concentration was assayed
      by high resolution liquid chromatography, and levels of plasma vitamin A lower
      than 20 microg/dL were defined as abnormal or deficient in vitamin A. Hemoglobin
      was measured by an automated cell counter, and anemia was defined as serum
      concentrations of less than 11.5 and 12.0 g/dL for children and adolescents,
      respectively. Nutritional status was assessed using z scores for weight/height,
      height/age and body mass index percentiles. RESULTS: The results indicated that
      33.55% of the schoolchildren tested had a vitamin A deficiency, with a prevalence
      of 35.44% among children (5-9 years) and 31.58% among adolescents (10-18 years).
      No correlation was observed between the prevalence of vitamin A deficiency and
      prevalence rates of anemia or malnutrition. Both sexes and all ages were
      homogeneous for vitamin A deficiency. CONCLUSIONS: The elevated prevalence of
      vitamin A deficiency among the children and adolescents attending this rural
      school identify a public health problem in the region. These results indicate
      that age groups from 5 years onwards should be included in those at risk of
      hypovitaminosis A and that they should be included in public policies aimed at
      combating hypovitaminosis A.

PMID- 17551656
TI  - Efficacy of new microprocessed phototherapy system with five high intensity light
      emitting diodes (Super LED).
AB  - OBJECTIVES: To evaluate the efficacy of a microprocessed phototherapy (PT) system
      with five high intensity light emitting diodes (Super LED) for the treatment of
      neonatal hyperbilirubinemia of premature infants. METHODS: Randomized clinical
      trial using Super LED phototherapy in the study group and twin halogen spotlight
      phototherapy in the control group. A stratified blocked randomization, based on
      birth weight, was performed. The duration of phototherapy and the rate of
      decrease of total serum bilirubin (TSB) concentration in the first 24 hours of
      treatment were the main outcome measures. RESULTS: We studied 88 infants, 44 in
      the Super LED group and 44 in the halogen spotlight PT group. The demographic
      characteristics of the patients in both groups were similar. Infants in the Super
      LED group had a similar mean initial serum bilirubin level (10.1+/-2.4 mg%) to
      those receiving halogen spotlight treatment (10.9+/-2.0 mg%). After 24 hours of
      treatment, the decrease in total serum bilirubin levels was significantly greater
      in the Super LED group (27.9 vs. 10.7%, p<0.01) and duration of phototherapy was
      significantly shorter in this group (36.8 h vs. 63.8 h, p<0.01). After 24 hours
      of treatment, a significantly greater number of patients receiving Super LED
      phototherapy had reached serum bilirubin concentrations low enough to allow
      withdrawal of treatment (23 vs. 10, p<0.01). CONCLUSIONS: Our results demonstrate
      that the efficacy of Super LED phototherapy for treating hyperbilirubinemia in
      premature infants was significantly better than halogen phototherapy.

PMID- 17551657
TI  - Renal involvement in Henoch-Schonlein purpura: a multivariate analysis of initial
      prognostic factors.
AB  - OBJECTIVES: To identify initial predictive factors of renal involvement in
      children and adolescents with Henoch-Schonlein purpura. METHODS: We reviewed the
      medical records of 142 patients admitted to our University Hospital over a 21
      year period with a diagnosis of Henoch-Schonlein purpura. The initial predictive
      factors assessed, observed during the first 3 months, included: demographic data,
      clinical manifestations (persistent palpable purpura, arthritis, abdominal pain,
      severe abdominal pain, gastrointestinal bleeding, orchitis, central nervous
      system involvement and pulmonary hemorrhage), laboratory tests (serum IgA levels)
      and treatment given (corticosteroids, intravenous immunoglobulin and
      immunosuppressive drugs). Patients were divided into two groups (presence or
      absence of nephritis) and assessed by univariate and multivariate analysis.
      RESULTS: Evidence of nephritis was detected in 70 patients (49.3%). The
      univariate analysis revealed that severe abdominal pain (p=0.0049; OR=1.6; 95%CI
      1.18-2.21), gastrointestinal bleeding (p=0.004; OR=1.6; 95%CI 1.10-2.26) and
      corticosteroid use (p=0.0012; OR=1.7; 95%CI 1.28-2.40) were all associated with
      increased incidence of renal involvement. In the multivariate analysis, logistic
      regression demonstrated that the only independent variable that predicted
      nephritis was intense abdominal pain (p<0.012; OR=2.593; 95%CI 1.234-5.452).
      CONCLUSIONS: Severe abdominal pain was a significant predictor of nephritis in
      Henoch-Schonlein purpura. Consequently, pediatric patients exhibiting this
      clinical manifestation should be rigorously monitored, due to the increased risk
      of renal involvement.

PMID- 17551658
TI  - Coagulation disorder in children and adolescents with moderate to severe
      traumatic brain injury.
AB  - OBJECTIVES: To describe the epidemiological profile of children and adolescents
      with moderate to severe traumatic brain injury admitted to an intensive care
      unit; to describe the frequency of coagulation disorders in these patients; to
      determine the relationship between coagulopathy and trauma severity; to assess
      the factors associated with coagulopathy; and to assess the effect of
      coagulopathy on the mortality of these patients. METHODS: Cross-sectional study
      with 301 patients aged up to 16 years admitted to an intensive care unit due to
      moderate to severe traumatic brain injury, carried out over a 5-year period. The
      coagulation profile was associated with clinical, epidemiological and CT
      findings. Univariate and multivariate analyses were used to check the association
      between coagulopathy and mortality. RESULTS: Minimum age was 23 days, and maximum
      age was 16 years (mean of 7.9 years). About 77% of patients had coagulopathy,
      whose occurrence was directly associated with the severity of the trauma, but not
      with the rise in mortality. The factors associated with the presence of
      coagulopathy were the following: severity of the traumatic brain injury (OR=2.83;
      95%CI 1.58-5.07), diagnosis of brain swelling on cranial computed tomography
      (OR=2.11; 95%CI 1.13-4.07) and occurrence of chest and/or abdominal injury
      (OR=2.07; 95%CI 1.11-4.00). Approximately 35% of patients died. The multivariate
      analysis showed that the factors associated with an increased risk of death were
      presence of sodium disorders (OR=5.56; 95%CI 2.90-10.65), hypotension in the
      intensive care unit (OR=12.58; 95%CI 4.40-35.00) and acute respiratory distress
      syndrome (OR=13.57; 95%CI 1.51-121.66). CONCLUSION: The development of
      coagulopathy is a frequent complication in patients with moderate to severe
      traumatic brain injury. Even though it is not closely associated with death in
      this study, it may be regarded as a marker of injury severity.

PMID- 17551659
TI  - Hospital mortality of very low birth weight newborn infants.

PMID- 17551661
TI  - Improvement in asthma endpoints when aiming for total control:
      salmeterol/fluticasone propionate versus fluticasone propionate alone.
AB  - AIMS: To investigate the magnitude of change in morning peak expiratory flow
      (PEF), asthma symptoms, and rescue beta2-agonist use, when the aim of treatment
      is to achieve guideline-defined control. METHODS: This was a protocol-defined
      analysis of data from the previously-reported one-year, stratified, randomised,
      double-blind, parallel-group GOAL study comparing the use of
      salmeterol/fluticasone propionate with fluticasone propionate alone in achieving
      guideline-defined control; this analysis assessed the magnitude of change in
      single specific endpoints which were amalgamated into the composite measure of
      control used in the primary GOAL analysis. RESULTS: Across all strata,
      improvements were seen for each outcome at 52 weeks as compared to baseline: mean
      morning PEF, 58.2 l/min (salmeterol/fluticasone propionate) versus 33.9 l/min
      (fluticasone propionate alone); symptom scores, -1.0 versus -0.8; symptom-free
      days, 72.5% versus 54.5%; mean of zero night awakenings, 31% versus 22%; rescue
      free days, 87.3 versus 74.7; annualised rate of severe exacerbations, 0.02 versus
      0.03; p<0.001 for all treatment differences. CONCLUSIONS: Aiming for guideline
      defined control resulted in sustained, clinically relevant improvements in a
      range of individual asthma outcomes. Improvements were greatest with
      salmeterol/fluticasone propionate versus fluticasone propionate alone.

PMID- 17551662
TI  - Calcipotriol and betamethasone dipropionate for the treatment of psoriasis: a 52
      week study.
AB  - Psoriasis is a common skin disease affecting 1%-3% of the world's population with
      significant impacts on quality of life. There is a great need for therapies that
      are efficacious and safe, not only for the short-term, but also for long-term
      management. Dovobet/ Daivobet/ Taclonex is a product combining two molecules,
      calcipotriol and betamethasone dipropionate, that may offer psoriatic patients
      with an option for maintenance therapy. The efficacy and safety of this combined
      formulation when used over a 4-week period is well documented. A recent
      publication in the British Journal of Dermatology discusses the safety of this
      product when used for 52 weeks.

PMID- 17551663
TI  - Drug treatments for skin disease introduced in 2006.
AB  - Drug Treatments for Skin Disease Introduced in 2006.

PMID- 17551664
TI  - Sorption of PAHs to colloid dispersions of humic substances in water.

PMID- 17551665
TI  - Pancreatographic investigation of the pancreatic duct system.
AB  - BACKGROUND: Embryologically, the pancreatic duct system develops by the fusion
      between the dorsal and ventral pancreatic bud ducts. It has been suggested that
      the proximal part of the main dorsal pancreatic duct partially regresses to form
      the accessory pancreatic duct (APD). Aim of this study was to clarify the anatomy
      of the pancreatic duct system of the head of the pancreas and investigate the
      embryology of the normal pancreatic duct system. METHODS: We reviewed endoscopic
      retrograde pancreatography of normal pancreatic heads (n = 256) and pancreas
      divisum (n = 36), focusing on long inferior branches arising from the APD and the
      main pancreatic duct (MPD). The accessory pancreatograms were divided into two
      patterns of course and shape, the long type (171 cases) and the short type (85
      cases) according to the length of the MPD from the orifice to the junction with
      the APD. The long-type APD formed a straight line and joined the MPD at the neck
      portion of the pancreas. The short-type APD joined the MPD near its first
      inferior branch. RESULTS: The shape of the long-type APD was quite similar to
      that of the dorsal pancreatic duct of pancreas divisum. The short-type APD was
      less likely to have a long inferior branch arising from the APD. The length of
      the APD from the orifice to the first long inferior branch was similar in the
      long-type APD (19.4 +/- 4.0 mm) and in the short-type APD (18.8 +/- 4.2 mm). The
      first long inferior branch from the long-type APD passed though the MPD near the
      origin of the inferior branch from the MPD, whereas the short-type APD joined the
      MPD near its inferior branch. CONCLUSIONS: There are two types of APD. The long
      type APD was quite similar to the shape of the dorsal pancreatic duct of pancreas
      divisum, and seems to represent a continuation of the main duct of the dorsal
      pancreatic bud. The short-type APD was less likely to have a long inferior
      branch, and seems to be formed by the most proximal part of the main duct of the
      dorsal pancreatic bud and its long inferior branch.

PMID- 17551667
TI  - Finite-stretching corrections to the Milner-Witten-Cates theory for polymer
      brushes.
AB  - This paper investigates finite-stretching corrections to the classical Milner
      Witten-Cates theory for semi-dilute polymer brushes in a good solvent. The
      dominant correction to the free energy originates from an entropic repulsion
      caused by the impenetrability of the grafting surface, which produces a depletion
      of segments extending a distance mu proportional to L(-1) from the substrate,
      where L is the classical brush height. The next most important correction is
      associated with the translational entropy of the chain ends, which creates the
      well-known tail where a small population of chains extend beyond the classical
      brush height by a distance xi proportional to L(-1/3). The validity of these
      corrections is confirmed by quantitative comparison with numerical self
      consistent field theory.

PMID- 17551668
TI  - The immediate effect of aerobic exercise on haemostatic parameters in patients
      with recently diagnosed mild to moderate essential hypertension.
AB  - BACKGROUND: Exercise is frequently recommended for the treatment of patients with
      arterial hypertension. Previous studies have shown an enhanced coagulation state
      after exercise. Our study investigates the alterations observed after a single
      session of submaximal aerobic exercise concerning coagulation, fibrinolysis,
      platelet activation as well as endothelial function in patients with recently
      diagnosed essential hypertension. METHODS: Twenty non-diabetic patients with
      recently diagnosed essential hypertension participated in a 45 min submaximal
      exercise test on a bicycle ergometer. Blood samples were drawn before and after
      exercise in order to determine parameters of coagulation activation (Prothrombin
      time [PT], activated Partial Thromboplastin time [aPTT], fibrinogen, D-Dimers,
      prothrombin fragments 1 + 2 [PF1+2], thrombin-antithrombin III complex [TAT] and
      factors VII, VIII and XII), platelet activation (Platelet count, Platelet factor
      4 [PF4] and beta-thromboglobulin [beta-TG]), fibrinolysis activation (Plasmin
      a(2) antiplasmin complex, PAP) and endothelial function (soluble Thrombomodulin
      [sTM] and von Willebrand factor [vWf]). Soluble P-selectin served as a marker for
      endothelial and platelet activation. RESULTS: All patients completed the exercise
      test. aPTT (P < 0.001) and factor VII (P = 0.01) significantly decreased while PT
      (P = 0.04), fibrinogen (P = 0.008), factor VIII (P < 0.001), platelet count (P =
      0.002) and beta-TG levels (P = 0.01) significantly increased as a result of
      exercise. Compared to baseline there was an 11% increase in TAT (P = 0.04) and a
      28% increase in PAP (P < 0.001) at peak exercise. One hour post exercise, there
      was a 43% increase in PAP whereas TAT levels became similar to those at baseline.
      Additionally vWf (P = 0.01) and sP-selectin (P = 0.02) levels significantly
      increased throughout the exercise protocol. CONCLUSIONS: Patients with recently
      diagnosed and never treated mild to moderate essential hypertension undergoing
      submaximal aerobic exercise present evidence of enhanced fibrinolysis compared
      with a mild increase of coagulation indices. However, whether there is a
      favourable effect of exercise on fibrinolysis over coagulation and/or endothelial
      involvement during exercise needs to be further investigated.

PMID- 17551669
TI  - Prostaglandin E2 enhances mitogen-activated protein kinase/Erk pathway in human
      cholangiocarcinoma cells: involvement of EP1 receptor, calcium and EGF receptors
      signaling.
AB  - COX-2-derived PGE2 has been implicated in the development of various types of
      cancers. However, the exact mechanism of PGE2-induced cancer cell proliferation
      and survival is still unclear. In the current study, the mechanism underlying
      PGE2-enhanced Erk phosphorylation in human cholangiocarcinoma cells was
      determined. The intracellular concentration of calcium in three
      cholangiocarcinoma cell lines was measured using a laser confocal scanning
      microscope and the expression levels of Erk and EGFR phosphorylation were
      determined by Western blot analyses. The activation of EP1 receptors involved in
      PGE2-stimulated Erk activation and increasing the intracellular concentration of
      calcium was elucidated using selective EP1 receptor subtype antagonists and
      agonist. The intracellular calcium chelator, BAPTA-AM, was shown to block PGE2
      induced Erk and EGFR phosphorylation. PGE2-induced Erk phosphorylation was
      abrogated by pretreatment with the EGF receptor kinase inhibitor, AG1478. Our
      findings suggest that in human cholangiocarcinoma cells, PGE2-enhanced
      phosphorylation of Erk is, at least in part, mediated through EP1 receptors and
      EGFR phosphorylation induced by increases in the intracellular concentration of
      calcium.

PMID- 17551670
TI  - Lipopolysaccharide induces expression of SSeCKS in rat lung microvascular
      endothelial cell.
AB  - Src-suppressed C kinase substrate (SSeCKS) plays a role in membrane-cytoskeletal
      remodeling to regulate mitogenesis, cell differentiation, and motility. Previous
      study showed that lipopolysaccharide (LPS) induced a selective and strong
      expression of SSeCKS in the vascular endothelial cells of lung. Here we show that
      LPS stimulation elevated expression of SSeCKS mRNA and protein in Rat pulmonary
      microvascular endothelial cell (RPMVEC). LPS potentiated SSeCKS phosphorylation
      in a time- and dose-dependent manner, and partly induced translocation of SSeCKS
      from the cytosol to the membrane after LPS challenge. The PKC inhibitor,
      Calphostin C, significantly decreased LPS-induced phosphorylation of SSeCKS,
      inhibited SSeCKS translocation and actin cytoskeleton reorganization after LPS
      challenge, suggesting that PKC may play a role in LPS-induced SSeCKS
      translocation and actin rearrangement. We conclude that SSeCKS is located
      downstream of PKC and that SSeCKS and PKC are both necessary for LPS-induced
      stress fiber formation.

PMID- 17551671
TI  - Application of the ELISPOT method for comparative analysis of interleukin (IL)-6
      and IL-10 secretion in peripheral blood of patients with astroglial tumors.
AB  - Glioblastoma, (grade IV astrocytoma), is characterized by rapid growth and
      resistance to treatment. Identification of markers of aggressiveness in this
      tumor could represent new therapeutic targets. Interleukins (IL)-6 and IL-10 may
      be considered as possible candidates, regulating cell growth, resistance to
      chemotherapy and angiogenesis. ELISPOT method provides a useful tool for the
      determination of the exact cell number of peripheral lymphocytes secreting a
      specific cytokine. IL-6 and IL-10 secretion levels were determined using ELISPOT
      methodology in peripheral blood mononuclear cells of 18 patients with astrocytic
      neoplasms (3 grade II and 15 grade IV), in parallel with 18 healthy controls.
      Additionally, immunohistochemical expression of these two cytokines was performed
      in paraffin-embedded neoplastic tissue in 12 of these patients. The secretion of
      IL-6 from peripheral monocytes was significantly higher in glioma patients
      compared to controls (P = 0.0003). In addition, IL-10 secretion from peripheral
      mononuclear and tumor cells of glioma patients was also higher as compared to
      healthy controls (P = 0.0002). Based on immunohistochemical staining, IL-6
      expression was localized in tumor cells and macrophages as well as in areas of
      large ischemic necrosis, while the major source of IL-10 expression in
      glioblastomas was the microglia/macrophage cells. It is suggested that IL-10
      contributes to the progression of astrocytomas by suppressing the patient's
      immune response, whereas IL-6 provides an additional growth advantage. This study
      demonstrates for the first time the usefulness of ELISPOT in estimating the
      secretion of IL-6 and IL-10 from peripheral blood and the correlation of their
      expression in neoplastic cells.

PMID- 17551672
TI  - Comparison between a coffee single copy chromosomal region and Arabidopsis
      duplicated counterparts evidenced high level synteny between the coffee genome
      and the ancestral Arabidopsis genome.
AB  - The Arabidopsis thaliana genome sequence provides a catalogue of reference genes
      that can be used for comparative analysis of other species thereby facilitating
      map-based cloning in economically important crops. We made use of a coffee
      bacterial artificial chromosome (BAC) contig linked to the S(H)3 leaf rust
      resistance gene to assess microsynteny between coffee (Coffea arabica L.) and
      Arabidopsis. Microsynteny was revealed and the matching counterparts to C.
      arabica contigs were seen to be scattered throughout four different syntenic
      segments of Arabidopsis on chromosomes (Ath) I, III, IV and V. Coffee BAC filter
      hybridizations were performed using coffee putative conserved orthologous
      sequences to Arabidopsis predicted genes located on the different Arabidopsis
      syntenic regions. The coffee BAC contig related to the S(H)3 region was
      successfully consolidated and later on validated by fingerprinting. Furthermore,
      the anchoring markers appeared in same order on the coffee BAC contigs and in all
      Arabidopsis segments with the exception of a single inversion on AtIII and AtIV
      Arabidopsis segments. However, the S(H)3 coffee region appears to be closer to
      the ancestral genome segment (before the divergence of Arabidopsis and coffee)
      than any of the duplicated counterparts in the present-day Arabidopsis genome.
      The genome duplication events at the origin of its Arabidopsis counterparts
      occurred most probably after the separation (i.e. 94 million years ago) of
      Euasterid (Coffee) and Eurosid (Arabidopsis).

PMID- 17551673
TI  - Molecular evolution and genome divergence at RPB2 gene of the St and H genome in
      Elymus species.
AB  - Molecular evolution of the second largest subunit of low copy nuclear RNA
      polymerase II (RPB2) in allotetrploid StH genomic species of Elymus is
      characterized here. Our study first reported a 39-bp MITE stowaway element
      insertion in the genic region of RPB2 gene for all tetraploid Elymus St genome
      and diploid Pseudoroegneria spicata and P. stipifolia St genome. The sequences on
      3'-end are highly conserved, with AGTA in all sequences but H10339 (E. fibrosis),
      in which the AGTA was replaced with AGAA. All 12 Stowaway-containing sequences
      encompassed a 9 bp conserved TIRs (GAGGGAGTA). Interestingly, the 5'-end sequence
      of GGTA which was changed to AGTA or deleted resulted in Stowaway excision in the
      H genome of Elymus sepcies, in which Stowaway excision did not leave footprint.
      Another two large insertions in all St genome sequences are also transposable
      like elements detected in the genic region of RPB2 gene. Our results indicated
      that these three transposable element indels have occurred prior to
      polyploidization, and shaped the homoeologous RPB2 loci in St and H genome of
      Eymus species. Nucleotide diversity analysis suggested that the RPB2 sequence may
      evolve faster in the polyploid species than in the diploids. Higher level of
      polymorphism and genome-specific amplicons generated by this gene indicated that
      RPB2 is an excellent tool for investigating the phylogeny and evolutionary
      dynamics of speciation, and the mode of polyploidy formation in Elymus species.

PMID- 17551674
TI  - Immunohistochemical changes in vulnerable rat brain regions after reversible
      global brain ischaemia.
AB  - Human global ischaemia was simulated in adult rats by inducing 20 min brain
      ischaemia and 60 min post-ischaemic recirculation. Immunohistochemical expression
      of MMP-9, TIMP-3, Bax and Bcl-2, and DNA fragmentation (with the TUNEL reaction)
      were investigated. The morphological data showed different neuronal responses in
      the hippocampus compared with the cerebral and cerebellar cortices. MMP-9
      immunoreactivity was different in the hippocampus, particularly in dentate gyrus
      and the CA1 region, compared with these cortices. Negative TIMP-3 staining in
      ischaemic hippocampal neurons may indicate a loss of its inhibitory activity on
      MMP-9 that could enhance cell death. Bcl-2 down regulation, Bax positivity and
      TUNEL+ type II cells in the dentate gyrus granular layer could be responsible for
      induction of apoptotic death in CA1 hippocampal pyramidal cells via loss of fibre
      input. Results suggest differential behaviours of neural cells after 60 min
      reperfusion.

PMID- 17551676
TI  - Uric acid: an old actor for a new role.

PMID- 17551677
TI  - Epidermal growth factor receptor tyrosine kinase inhibitors for the treatment of
      non-small-cell lung cancer: results and open issues.
AB  - The medical treatment of non-small-cell lung cancer (NSCLC) has progressively
      changed since the introduction of "targeted therapy". The development of one of
      these molecular drug categories, e. g., the epidermal growth factor receptor
      (EGFR) tyrosine-kinase (TK) selective inhibitors, such as the orally active
      gefitinib and erlotinib, offers an interesting new opportunity. The clinical
      response rates obtained with their employment in unselected patient populations
      only account for approximately 10%. Because of this, over the last two years
      numerous studies have been performed in order to identify the patient subsets
      that could better benefit from these agents. Not only patient characteristics and
      clinical-pathological features, such as never-smoking status, female gender, East
      Asian origin, adenocarcinoma histology, bronchioloalveolar subtype, but also
      molecular findings, such as somatic mutations in the EGFR gene, emerge as
      potentially useful prognostic and predictive factors in advanced NSCLC. Further,
      specifically designed clinical trials are still needed to completely clarify
      these and other open issues that are reviewed in this paper, in order to clarify
      all the interesting findings available in the clinical practice.

PMID- 17551678
TI  - The treatment of polycythaemia vera: an update in the JAK2 era.
AB  - The clinical course of polycythaemia vera is marked by a high incidence of
      thrombotic complications, which represent the main cause of morbidity and
      mortality. Major predictors of vascular events are increasing age and previous
      thrombosis. Myelosuppressive drugs can reduce the rate of thrombosis, but there
      is concern that their use raises the risk of transformation into acute leukaemia.
      To tackle this dilemma, a risk-oriented management strategy is recommended. Low
      risk patients should be treated with phlebotomy and low-dose aspirin. Cytotoxic
      therapy is indicated in high-risk patients, with the drug of choice being
      hydroxyurea because its leukaemogenicity is low. The recent discovery of JAK2
      V617F mutation in the vast majority of polycythaemia vera patients opens new
      avenues for the treatment of this disease. Novel therapeutic options
      theoretically devoid of leukaemic risk, such as alpha-interferon and imatinib,
      affect JAK2 expression in some patients. Nevertheless, these drugs require
      further clinical experience and, for the time being, should be reserved for
      selected cases.

PMID- 17551679
TI  - Relation between serum uric acid and carotid intima-media thickness in healthy
      postmenopausal women.
AB  - OBJECTIVE: Serum uric acid (SUA) is associated with cardiovascular disease (CVD).
      However it is still disputed whether the relationship is mediated by other risk
      factors such as obesity, dyslipidaemia, hypertension and insulin resistance. We
      explored the association of the uric acid level with carotid intima-media
      thickness (IMT), a well known marker of CVD, in postmenopausal healthy women.
      METHODS: We consecutively enrolled postmenopausal women undergoing a screening
      for health evaluation. After an accurate clinical examination, and a biochemical
      evaluation, the enrolled subjects underwent B mode ultrasonography to assess
      common carotid intima media thickness. RESULTS: Among 234 women aged 45-70 years,
      the uric acid level is associated with carotid IMT independently of other
      prognostic factors (p=0.03). In particular, women in the highest tertiles of uric
      acid level have a greater IMT than women in the lowest tertile (p=0.007).
      CONCLUSIONS: Independently of other cardiovascular risk factors, SUA levels are
      associated with carotid IMT even in subjects without the metabolic syndrome. This
      confirms and expands the role of uric acid in the determinism of CVD. Prospective
      trials would be useful to evaluate interventions aimed at lowering the uric acid
      level.

PMID- 17551680
TI  - Underuse of oral anticoagulants in patients with nonvalvular atrial fibrillation
      in Italy.
AB  - INTRODUCTION: Oral anticoagulants (OAs) are significantly more effective than
      Aspirin in the prevention of cerebrovascular accidents among patients with atrial
      fibrillation (AF). Several studies, however, showed OAs to be widely underused in
      these patients. OBJECTIVE: To assess the appropriateness of antithrombotic
      therapy in an Italian population of AF patients. METHODS: Two hundred and fifty
      five consecutive patients affected by nonvalvular AF participated in the study.
      Data were collected on demographic characteristics, risk factors for stroke,
      current prophylactic therapy, and perceived or actual risk factors for bleeding.
      INR levels were measured. Patients were stratified by their risk for stroke (214
      at high risk, 21 moderate, 20 low), and their prophylactic therapy was analysed
      in light of international antithrombotic therapy recommendations. After therapy
      adjustment, 203 of our patients were followed-up for the occurrence of
      cerebrovascular events for an average of 27 months. RESULTS: Upon admission, 35%
      (n=75) of patients in the high-risk category were either taking no antithrombotic
      prophylaxis or were being treated with Aspirin. In addition, 38 of 139 patients
      receiving OAs had an INR<2. Thus, a total of 113 (52.8%) high-risk subjects were
      not receiving adequate antithrombotic therapy. Of high-risk patients not treated
      with OAs, 46.7% reported no perceived or actual risk factors for bleeding. The
      annual incidence of cerebrovascular accidents was 3.8% among 163 high-risk
      patients assigned to OA treatment, and 4.5% among 39 patients given Aspirin
      treatment. Relative to expected annual incidence rates, cerebrovascular risk in
      anticoagulated patients was reduced by about 70%. CONCLUSIONS: Underuse of OAs is
      still common in Italy, and much of it cannot be explained by the concern for
      haemorrhage. Support and training in the complex task of anticoagulation
      management may help to extend this efficacious prophylactic therapy to all
      patients who may benefit from it.

PMID- 17551681
TI  - An unusual case presenting with hypertensive crisis.

PMID- 17551682
TI  - Pulsus paradoxus: an underused tool.

PMID- 17551683
TI  - Intracerebral haemorrhage - initial actions are critical.

PMID- 17551685
TI  - The yield of head CT in syncope: a pilot study.
AB  - Although head CT is often routinely performed in emergency department (ED)
      patients with syncope, few studies have assessed its value. OBJECTIVES: To
      determine the yield of routine head CT in ED patients with syncope and analyse
      the factors associated with a positive CT. METHODS: Prospective, observational,
      cohort study of consecutive patients presenting with syncope to an urban tertiary
      care ED (48,000 annual visits). INCLUSION CRITERIA: age >or=18 and loss of
      consciousness (LOC). Exclusion criteria included persistent altered mental
      status, drug-related or post-trauma LOC, seizure or hypoglycaemia. Primary
      outcome was abnormal head CT including subarachnoid, subdural or parenchymal
      haemorrhage, infarction, signs of acute stroke and newly diagnosed brain mass.
      RESULTS: Of 293 eligible patients, 113 (39%) underwent head CT and comprise the
      study cohort. Ninety-five patients (84%) were admitted to the hospital. Five
      patients, 5% (95% CI=0.8%-8%), had an abnormal head CT: 2 subarachnoid
      haemorrhage, 2 cerebral haemorrhage and 1 stroke. Post hoc examination of
      patients with an abnormal head CT revealed focal neurologic findings in 2 and a
      new headache in 1. The remaining 2 patients had no new neurologic findings but
      physical findings of trauma (head lacerations with periorbital ecchymoses
      suggestive of orbital fractures). All patients with positive findings on CT were
      >65 years of age. Of the 108 remaining patients who had head CT, 45 (32%-51%) had
      signs or symptoms of neurologic disease including headache, trauma above the
      clavicles or took coumadin. Limiting head CT to this population would potentially
      reduce scans by 56% (47%-65%). If age >60 were an additional criteria, scans
      would be reduced by 24% (16%-32%). Of the patients who did not have head CT, none
      were found to have new neurologic disease during hospitalisation or 30-day follow
      up. CONCLUSIONS: Our data suggest that the derivation of a prospectively derived
      decision rule has the potential to decrease the routine use of head CT in
      patients presenting to the ED with syncope.

PMID- 17551686
TI  - A 29-year-old man with subcutaneous emphysema of the neck following blunt trauma.

PMID- 17551684
TI  - Intracerebral haemorrhage: an often neglected medical emergency.
AB  - Intracerebral haemorrhage (ICH) is the deadliest form of stroke, carrying a
      mortality rate between 30% and 55%, increasing to 67% in patients on oral
      anticoagulant therapy (OAT). Despite its relevant incidence, the treatment of ICH
      has been until recently a largely neglected item, addressed by only a few trials.
      Early treatment of ICH in non-anticoagulated patients with recombinant activated
      factor VII (rFVII) has been demonstrated to be able to limit the growth of the
      haematoma, but such a promising result requires further confirmations. In ICH
      patients receiving OAT a prompt reversal of the anticoagulant effect should be
      warranted in order to reduce the consequences of this dreadful adverse event. In
      clinical practice, however, just a small proportion of anticoagulated patients
      receive this treatment, probably because of the fear of thromboembolic
      complications. It is now time to check our way of thinking about ICH, regarding
      and treating it as a compelling medical emergency.

PMID- 17551687
TI  - An unusual cause of chest pain.

PMID- 17551688
TI  - Systematic reviews highlight the complex balance between good and harm from
      screening studies.

PMID- 17551690
TI  - Hypertension and reduced renal function: a rebuttal.

PMID- 17551691
TI  - More on hypertension and reduced renal function.

PMID- 17551692
TI  - Bilateral posterior shoulder dislocations following seizure.

PMID- 17551693
TI  - Amino acid sequence homologies between HCV polyprotein and thyroid antigens.

PMID- 17551694
TI  - Transient massive hyperlipidaemia in a type 2 diabetic subject.

PMID- 17551695
TI  - D-dimer testing: advantages and limitations in emergency medicine for managing
      acute venous thromboembolism.

PMID- 17551696
TI  - Polyphenols and cancer cell growth.
AB  - Polyphenols constitute an important group of phytochemicals that gained increased
      research attention since it was found that they could affect cancer cell growth.
      Initial evidence came from epidemiologic studies suggesting that a diet that
      includes regular consumption of fruits and vegetables (rich in polyphenols)
      significantly reduces the risk of many cancers. In the present work we briefly
      review the effects of polyphenols on cancer cell fate, leading towards growth,
      differentiation and apoptosis. Their action can be attributed not only to their
      ability to act as antioxidants but also to their ability to interact with basic
      cellular mechanisms. Such interactions include interference with membrane and
      intracellular receptors, modulation of signaling cascades, interaction with the
      basic enzymes involved in tumor promotion and metastasis, interaction with
      oncogenes and oncoproteins, and, finally, direct or indirect interactions with
      nucleic acids and nucleoproteins. These actions involve almost the whole spectrum
      of basic cellular machinery--from the cell membrane to signaling cytoplasmic
      molecules and to the major nuclear components--and provide insights into their
      beneficial health effects. In addition, the actions justify the scientific
      interest in this class of compounds, and provide clues about their possible
      pharmaceutical exploitation in the field of oncology.

PMID- 17551698
TI  - [Role expectations of various professional groups in the operating theatre].
AB  - BACKGROUND: Clearly defined professional roles have the advantage that team
      members know what they are expected to do and what their expectations of other
      professional groups are. For the definition of roles a distinct number of
      interactions between persons are a prerequisite. In a typical operations room
      (OR) team members are not constantly involved and are often exchanged.
      Interactions between personnel are not strong enough to fulfil the designing
      process of role shaping. In this study the possible substitution of defined roles
      by a distinct professional culture in an OR was studied. METHODS: Using a
      shortened form of the SYMLOG questionnaire, 179 persons working in the ORs of 2
      Swiss hospitals were interviewed. The three main professional groups in the OR
      setting were represented in this cohort: anaesthesia personnel (physicians and
      nurses), surgeons and operating room technicians and nurses. The SYMLOG
      questionnaire allows the rating of sympathy, influence and goal orientation of
      the professional groups. RESULTS: Surgeons and anaesthetists had the strongest
      influence and higher ratings for goal orientation. In comparison, the influence
      of members of the nursing profession was less valued. All three professional
      groups rated themselves higher than in the perception of the other professional
      groups. CONCLUSIONS: It is concluded that in this analysis the role definition
      was not clear. Optimization is therefore possible which could reduce conflict
      potential and contribute to a higher productivity.

PMID- 17551699
TI  - [Comparison of premedication regimes. A randomized, controlled trial].
AB  - BACKGROUND: The effect of two premedication regimes with different
      benzodiazepines on anxiety, hemodynamic data, sympatho-adrenal activity, and
      bispectral index (BIS) was evaluated during the variable time period prior to
      induction of anesthesia. PATIENTS AND METHODS: This prospective, double-blind
      study was performed with 50 ASA class I and II patients. Patients were randomized
      either to group I: evenings 22.00 hours 50 mg chlorazepate dipotassium (CD),
      mornings 07.00 hours 25 mg CD, placebo 30 min prior to anesthesia (on demand) or
      group II: evenings 50 mg CD, mornings placebo, 7.5 mg midazolam on demand.
      RESULTS: In group I the BIS dropped after administration of 25 mg CD and was
      significantly lower at 08.00, 09.00 and 10.00 hours compared to baseline (mean+/
      SD; 90+/-5, 87+/-7 and 87+/-7, respectively vs. 95+/-4; p<0.05), whereas the BIS
      of group II did not decrease significantly. Both groups did not differ
      significantly with respect to all variables obtained throughout the study period.
      CONCLUSION: We conclude that 50 mg CD the evening before surgery prevented an
      increase of anxiety and sympatho-adrenal activity in both groups and might
      therefore be sufficient as premedication. Fixed time application of 25 mg CD at
      07.00 hours or 7.5 mg midazolam 30 min prior to anesthesia did not further affect
      these variables preoperatively.

PMID- 17551700
TI  - [Keratosis follicularis spinulosa decalvans].
AB  - Keratosis follicularis spinulosa decalvans is a rare, X-linked disorder of
      keratinization of the hair follicle with inflammation and atrophy associated with
      corneal dystrophy and other symptoms. A family with several affected members is
      reported. The unaffected parents were related. A 12-year-old girl and her 5-year
      old brother had follicular spiny hyperkeratoses on the trunk and extremities. The
      girl had thinning of the eyelashes and eyebrows as well as scarring alopecia of
      the scalp as additional features of the disease. Both the girl and her brother
      had corneal dystrophy and photophobia. Two sisters aged 8 and 10 years did not
      show similar skin or eye findings.

PMID- 17551701
TI  - [The relationship between minimal pair reproduction and writing skills].
AB  - OBJECTIVE: It is generally accepted that dyslexia arises due to deficits in
      phonological processing. However, whether these deficits are based on impaired
      auditory processing is still subject to debate. Here we tested whether low level
      auditory processing is correlated with a simple phonological processing task,
      thus indicating a close relationship between higher sensory and lower cognitive
      processing. METHODS: We carried out a prospective study with 200 school children
      attending the third and fourth grades. The dependent variables used were just
      noticeable differences in intensity and frequency (JNDI, JNDF), gap detection
      (GD), monaural and binaural temporal order judgment (TOJ(b) and TOJ(m)), minimal
      pair perception and reproduction skills for real words and nonsense words.
      RESULTS: No relevant correlation was found between any auditory low level
      processing variable and minimal pair representation and reproduction skills.
      DISCUSSION: These data do not support the auditory processing deficit theory.

PMID- 17551702
TI  - [Minimal pair reproduction correlates with spelling ability].
AB  - OBJECTIVE: It has not yet been possible to explain definitively why some children
      find it especially difficult to acquire written language skills. Taking the
      phonological deficit theory as a basis, minimal pair reproduction, i.e. a simple
      phonological task, was measured in schoolchildren and compared with their
      spelling performance. METHODS: In a cross-sectional investigation minimal pair
      and/or minimal triplet reproduction (real words and nonsense words) was measured
      in 200 schoolchildren in the third or fourth school year. The children's marks
      for spelling, German and mathematics were also recorded. RESULTS: There were
      significant correlations between performance in phonological reproduction and
      spelling, but not between phonological reproduction and the other marks.
      DISCUSSION: These empirically ascertained data add credence to the phonological
      deficit theory. It appears that phonological deficits can be revealed by
      relatively simple tasks that concern the representation of speech sounds rather
      than the ability to use these sounds. This suggests that the interface between
      auditory/sensory and cognitive/operational processing is deficient in the
      children affected.

PMID- 17551704
TI  - [Physicians' strike for internationally comparable salaries. Analysis of the
      opposition to the German public sector collective agreements and the new pay and
      conditions agreements for physicians].

PMID- 17551705
TI  - The effect of larval and early adult experience on behavioural plasticity of the
      aphid parasitoid Aphidius ervi (Hymenoptera, Braconidae, Aphidiinae).
AB  - The relevance of the integration of preimaginal and eclosion experiences on the
      subsequent habitat preferences and mate finding by the adult has been rarely
      tested in holometabolous insects. In this work, the effect of larval and early
      adult experiences on the behavioural responses of adult males of the aphid
      parasitoid, Aphidius ervi, towards volatiles from the host-plant complex (HPC)
      and from conspecific females were evaluated. Two experience factors were
      considered: host diet (normal diet=ND; artificial diet=AD), and eclosion, i.e.
      extraction or non-extraction of the parasitoid larva from the parasitised aphid
      (extracted=EX; non-extracted=NE). Thus, four treatments were set up: ND/NE,
      ND/EX, AD/NE and AD/EX. Glass Y-tube olfactometers were used to investigate the
      responses of adult A. ervi males to the odour sources used. Males from the ND/NE
      treatment showed a shorter latency to the first choice of olfactometer arms,
      displayed a marked preference towards the HPC olfactometer arm, and spent more
      time in the HPC arm than males from the other treatments. Only the interaction of
      host diet and eclosion experiences proved to be relevant in explaining the
      differences in latency to first choice, time spent in olfactometers arms, and
      behaviours displayed in the olfactometer arms. These results show the importance
      of the integration of larval and eclosion experiences in the development of
      stereotyped responses of the adults. This process may involve memory retention
      from the preimaginal and emergence period, but further research is needed to
      disentangle the contribution of each stage. The response to conspecific females
      was much less affected by the treatments in relation to first arm choice and
      times in olfactometer arms, suggesting a pheromone-mediated behaviour, even
      though a prompter and more intense wing fanning courtship behaviour was
      registered in the ND/NE males compared to males from the AD/NE treatment. These
      results show that sexual behaviours are less affected by early experiences than
      behaviours related with finding a HPC for foraging or oviposition. Taken
      together, our results demonstrate for first time that larval and eclosion
      experiences affect in a differential way the early responses of the adult towards
      environment-derived cues and mate related cues.

PMID- 17551706
TI  - Clonal structure affects the assembling behavior in the Japanese queenless ant
      Pristomyrmex punctatus.
AB  - The queenless ant Pristomyrmex punctatus (Hymenoptera: Myrmicinae) has a unique
      society that differs from those of other typical ants. This species does not have
      a queen, and the workers lay eggs and produce their clones parthenogenetically.
      However, a colony of these ants does not always comprise members derived from a
      single clonal line. In this study, we examined whether P. punctatus changes its
      "assembling behavior" based on colony genetic structure. We prepared two
      subcolonies--a larger one comprising 200 individuals and a smaller one comprising
      100 individuals; these subcolonies were established from a single stock colony.
      We investigated whether these subcolonies assemble into a single nest. The
      genetically monomorphic subcolonies (single clonal line) always fused into a
      single nest; however, the genetically polymorphic subcolonies (multiple clonal
      lines) did not tend to form a single colony. The present study is the first to
      demonstrate that the colony genetic structure significantly affects social
      viscosity in social insects.

PMID- 17551707
TI  - [In memoriam Prof. Dr. Rudolf Max Hess].

PMID- 17551709
TI  - [Tumors and tumor-like lesions].
AB  - Tumors and tumor-like lesions are rare diseases in the paranasal sinuses. There
      is a great variety of histological types, but only a small number of
      morphological patterns on imaging. Histology is an important point in therapeutic
      planning. In most cases it is obtained by sampling, which is not as difficult in
      the sinonasal area as in other regions of the body. The main task of imaging is
      an exact estimation of the extent and spread of a lesion. This article discusses
      the possibilities and limitations of CT and MRI in the assessment of the dignity
      and spread of paranasal tumors and tumor-like lesions in consideration of
      necessary therapeutic information. Additionally, an overview of features on
      imaging of different paranasal tumors and tumor-like lesions is given.

PMID- 17551710
TI  - High-resolution mapping of the Alp locus and identification of a candidate gene
      HvMATE controlling aluminium tolerance in barley (Hordeum vulgare L.).
AB  - Aluminium (Al) tolerance in barley is conditioned by the Alp locus on the long
      arm of chromosome 4H, which is associated with Al-activated release of citrate
      from roots. We developed a high-resolution map of the Alp locus using 132 doubled
      haploid (DH) lines from a cross between Dayton (Al-tolerant) and Zhepi 2 (Al
      sensitive) and 2,070 F(2 )individuals from a cross between Dayton and Gairdner
      (Al-sensitive). The Al-activated efflux of citrate from the root apices of Al
      tolerant Dayton was 10-fold greater than from the Al-sensitive parents Zhepi 2
      and Gairdner. A suite of markers (ABG715, Bmag353, GBM1071, GWM165, HvMATE and
      HvGABP) exhibited complete linkage with the Alp locus in the DH population
      accounting 72% of the variation for Al tolerance evaluated as relative root
      elongation. These markers were used to map this genomic region in the
      Dayton/Gairdner population in more detail. Flanking markers HvGABP and ABG715
      delineated the Alp locus to a 0.2 cM interval. Since the HvMATE marker was not
      polymorphic in the Dayton/Gairdner population we instead investigated the
      expression of the HvMATE gene. Relative expression of the HvMATE gene was 30-fold
      greater in Dayton than Gardiner. Furthermore, HvMATE expression in the F(2:3)
      families tested, including all the informative recombinant lines identified
      between HvGABP and ABG715 was significantly correlated with Al tolerance and Al
      activated citrate efflux. These results identify HvMATE, a gene encoding a
      multidrug and toxic compound extrusion protein, as a candidate controlling Al
      tolerance in barley.

PMID- 17551711
TI  - Lateral unicompartmental knee replacement: fixed or mobile bearing?
AB  - Between May 2001 and May 2003, 233 consecutive Preservation unicompartmental knee
      replacements (UKR) were performed. Of these, 30 were lateral UKRs (13%) performed
      in 12 men and 16 women (2 bilateral cases) with a mean age of 67 years (range 36
      93 years). A metal-backed mobile bearing tibial component was used in 13 knees
      and an all-polyethylene fixed bearing tibial component in 17 knees. The patients
      were reviewed prospectively at 1 and 2 years. The 2 year results show no
      difference in range of motion or function between the mobile and fixed bearing
      versions of the Preservation knee when used on the lateral side. There were three
      early revisions, all in the mobile bearing group.

PMID- 17551712
TI  - DNA bipyrimidine photoproduct repair and transcriptional response of UV-C
      irradiated Bacillus subtilis.
AB  - Vegetative wild-type and DNA repair-deficient (homologous recombination, recA and
      nucleotide excision repair, uvrB) Bacillus subtilis cells were exposed to UV-C
      radiation. Colony formation, DNA bipyrimidine photoproducts and gene expression
      were measured during cell recovery. Gene expression was measured after 60 min
      cell recovery where 50% (wild-type), 30% (recA) and 8% (uvrB), respectively, of
      the UV-C induced DNA photoproducts were repaired. We examined changes in the gene
      expression following UV exposure in wild-type and both repair-deficient strains.
      A set of known and unknown genes were found to be significantly up-regulated in
      wild-type B. subtilis cells, whereas no or lower gene induction was determined
      for both mutant strains. In addition, the possible roles of newly identified UV
      responsive genes are discussed with respect to cellular recovery following
      exposure to UV irradiation.

PMID- 17551708
TI  - [Update on pathophysiologic and immunotherapeutic approaches for the treatment of
      multiple sclerosis].
AB  - Multiple sclerosis (MS) is a chronic disabling disease with significant
      implications for patients and society. The individual disease course is difficult
      to predict due to the heterogeneity of clinical presentation and of radiologic
      and pathologic findings. Although its etiology still remains unknown, the last
      decade has brought considerable understanding of the underlying pathophysiology
      of MS. In addition to its acceptance as a prototypic inflammatory autoimmune
      disorder, recent data reveal the importance of primary and secondary
      neurodegenerative mechanisms such as oligodendrocyte death, axonal loss, and ion
      channel dysfunction. The deepened understanding of its immunopathogenesis and the
      limited effectiveness of currently approved disease-modifying therapies have led
      to a tremendous number of trials investigating potential new drugs. Emerging
      treatments take into account the different immunopathological mechanisms and
      strategies, to protect against axonal damage and promote remyelination. This
      review provides a compilation of novel immunotherapeutic strategies and recently
      uncovered aspects of known immunotherapeutic agents. The pathogenetic rationale
      of these novel drugs for the treatment of MS and accompanying preclinical and
      clinical data are highlighted.

PMID- 17551713
TI  - Regulation of expression of Na+ -translocating NADH:quinone oxidoreductase genes
      in Vibrio harveyi and Klebsiella pneumoniae.
AB  - The expression of genes encoding sodium-translocating NADH:quinone oxidoreductase
      (Na(+)-NQR) was studied in the marine bacterium Vibrio harveyi and in the
      enterobacterium Klebsiella pneumoniae. It has been shown that such parameters as
      NaCl concentration, pH value, and presence of an uncoupler in the growth media do
      not influence significantly the level of nqr expression. However, nqr expression
      depends on the growth substrates used by these bacteria. Na(+)-NQR is highly
      repressed in V. harveyi during anaerobic growth, and nqr expression is modulated
      by electron acceptors and values of their redox potentials. The latter effect was
      shown to be independent of the ArcAB regulatory system.

PMID- 17551714
TI  - Effects of the flavonoids kaempferol and fisetin on thermotolerance, oxidative
      stress and FoxO transcription factor DAF-16 in the model organism Caenorhabditis
      elegans.
AB  - Flavonoids present in many herbal edibles possess a remarkable spectrum of
      biochemical and pharmacological actions and they are assumed to exert beneficial
      effects to human health. Although the precise biological mechanisms of their
      action has not been elucidated yet many of the protective properties of
      flavonoids are attributed to their antioxidative activity since oxidative stress
      is regarded as a main factor in the pathophysiology of various diseases and
      ageing. Oxidative stress results from excessive generation of reactive oxygen
      species (ROS) or diminished antioxidative defence and thus antioxidants are able
      to counteract such situations. We used the multicellular model organism
      Caenorhabditis elegans that is conserved in molecular and cellular pathways to
      mammals to examine the effects of the flavonoids kaempferol and fisetin with
      respect to their protective action in individual living worms. Both flavonoids
      increased the survival of C. elegans, reduced the intracellular ROS accumulation
      at lethal thermal stress, and diminished the extent of induced oxidative stress
      with kaempferol having a stronger impact. Kaempferol but not fisetin attenuated
      the accumulation of the ageing marker lipofuscin suggesting a life prolonging
      activity of this flavonoid. In addition to these effects that may be attributed
      to their antioxidative potential kaempferol and fisetin caused a translocation of
      the C. elegans FoxO transcription factor DAF-16 from the cytosol to the nucleus
      indicating a modulatory influence of both flavonoids on signalling cascade(s).

PMID- 17551715
TI  - Determination of molar absorptivity coefficients for major type-B trichothecenes
      and certification of calibrators for deoxynivalenol and nivalenol.
AB  - This paper presents results from the European Commission-funded project
      Doncalibrant, the objective of which was to produce calibrators with certified
      mass fractions of the Fusarium toxins deoxynivalenol (DON), 3
      acetyldeoxynivalenol (3-Ac-DON), 15-acetyldeoxynivalenol (15-Ac-DON), and
      nivalenol (NIV), in acetonitrile. The calibrators, available in ampoules, were
      sufficiently homogeneous, with between-bottle variations (s (bb)) of less than
      2%. Long-term stability studies performed at four different temperatures between 
      18 and 40 degrees C revealed no significant negative trends (at a confidence
      level of 95%). Molar absorptivity coefficients (in L mol(-1) cm(-1)) were
      determined for all four toxins (DON: 6805 +/- 126, NIV: 6955 +/- 205, 3-Ac-DON:
      6983 +/- 141, 15-Ac-DON: 6935 +/- 142) on the basis of a mini-interlaboratory
      exercise. The overall uncertainty of the calibrators' target values for DON and
      NIV were evaluated on the basis of gravimetric preparation data and include
      uncertainty contributions from possible heterogeneity, storage, and transport.
      The Doncalibrant project resulted in the production of calibrators for DON (IRMM
      315) and NIV (IRMM-316) in acetonitrile with certified mass fractions of 25.1 +/-
      1.2 microg g(-1) and 24.0 +/- 1.1 microg g(-1), respectively. Both CRMs became
      commercially available from the Institute for Reference Materials and
      Measurements (IRMM, Geel, Belgium) at the beginning of 2007.

PMID- 17551716
TI  - Combination of analytical and microbiological techniques to study the
      antimicrobial activity of a new active food packaging containing cinnamon or
      oregano against E. coli and S. aureus.
AB  - The aim of this work is the optimization and application of a group of analytical
      and microbiological techniques in the study of the activity of essential oils
      (EOs) incorporated in a new antimicrobial packaging material and the research in
      depth of the interaction between the microbial cells and the individual compounds
      present in the active material. For this purpose the antimicrobial activity of
      the active packaging containing cinnamon or oregano was evaluated against E. coli
      and S. aureus. The vapour phase activity and the direct contact between the
      antimicrobial agents themselves, or once incorporated in the packaging material,
      and the microbial cells have been studied. The direct contact was studied using a
      broth dilution method. The vapour phase was evaluated by using a new method which
      involves the use of a filter disk containing the EOs. Furthermore, the kill time
      assay was used to determine the exposure time for the maximum efficiency in
      packaging, and transmission electron microscopy was used to investigate the
      antimicrobial activity and the possible mechanism of action against E. coli and
      S. aureus. Finally, the compounds absorbed by cells were identified. The results
      showed that the techniques used provide relevant information about the
      antibacterial activity of cinnamon and oregano in direct contact as well as in
      the vapour phase. The antimicrobial packaging showed a fast efficiency which
      supports its likely application as a food packaging material. Bacteria treated
      with EOs exhibit a wide range of significant abnormalities; these include
      formation of blebs, coagulation of cytoplasmatic constituents, collapse of the
      cell structure and lack of cytoplasmatic material. Some of these observations are
      correlated to the ability of some of these substances to disrupt envelop
      structure, especially the inner membrane. After an extraction from dead cells,
      cinnamaldehyde was detected by GC-MS in E. coli exposed to the active packaging
      containing cinnamon.

PMID- 17551717
TI  - Molecularly imprinted microspheres and nanospheres for di(2-ethylhexyl)phthalate
      prepared by precipitation polymerization.
AB  - Molecularly imprinted microspheres (MIMs, >3 microm) and nanospheres (MINs,
      approximately 450 nm) for the environmental endocrine disruptor di(2
      ethylhexyl)phthalate (DEHP) were prepared by a precipitation polymerization (PP)
      procedure. The effect of the dispersive solvents acetonitrile (ACN) and
      cyclohexane (CH), the cross-linkers ethylene glycol dimethacrylate (EDMA) and
      trimethylpropane trimethacrylate (TRIM), and the template on particle size and
      morphology of polymers was investigated in detail by scanning electron microscopy
      (SEM) and BET adsorption isotherm determination. When used as HPLC stationary
      phase, the microspheres exhibited strong affinity for the template DEHP with an
      imprint factor (IF) higher than 8.0 in ACN/water (60:40, v/v) as mobile phase.
      Furthermore, baseline separation of DEHP from benzyl butyl phthalate (BBP) and
      dibutyl phthalate (DBP) could be achieved. In contrast, no or only poor
      separation could be observed with non-imprinted polymeric polymers (NIPs) or
      imprinted bulk polymers (MIB), respectively. Similarly, the obtained MINs
      exhibited an imprinting effect in pure ACN, i.e. the bond amount of DEHP was
      significantly higher compared to NIPs, as was shown in rebinding experiments.
      Besides their use as an HPLC stationary phase, MIMs might further be applicable
      for SPE sample cleanup, while MINs could be used as a recognition layer on sensor
      surfaces.

PMID- 17551718
TI  - Age-related changes in avoidance strategies when negotiating single and multiple
      obstacles.
AB  - The aim of this research was to describe age-related changes in locomotor
      adjustments during obstructed gait and expand and build from the current body of
      literature describing single obstacle avoidance strategies by including trials in
      which the subjects stepped over two identical obstacles placed in series. We
      observed young adults (YA: N = 8; aged 23.1 +/- 2.0 years) and older adults (OA:
      N = 8; aged 76.1 +/- 4.3 years) as they walked along a 5 m long instrumented
      pathway (GAITRite) and stepped over one or two obstacles that were scaled to
      their lower leg length. Infrared markers, tracked using the Optotrak motion
      analysis system (60 Hz; Northern Digital Inc, Canada), were fixed to subjects'
      trunk and feet, and several anatomical landmarks were digitized for each segment
      (e.g. toes). Data analyses included lead and trail toe clearance values, take-off
      and landing distance, step time, length, width and velocity, and three
      dimensional trunk angles. Both age groups were able to successfully complete the
      obstacle avoidance task, and the presence of a second obstacle did not affect
      clearance strategies of either OA or YA. OA crossed the obstacles with a reduced
      step velocity and stepped closer to the trailing edge, although take-off
      distances were not different between the age groups. Additionally, OA used
      similar ranges of trunk motion as YA when crossing the obstacle, but did so while
      using smaller step lengths and step widths compared to YA, effectively, using a
      narrower base of support. Together, these findings suggest that older adults
      adopted a more cautious crossing strategy in that they reduced their crossing
      step velocity. However, other aspects of the avoidance strategy used by the older
      adults, specifically the shortened landing distances and the use of similar
      ranges of trunk motion within a narrowed BOS, could potentially put them at risk
      for tripping or imbalance when stepping over an obstacle.

PMID- 17551719
TI  - Experimental muscle pain decreases the frequency threshold of electrically
      elicited muscle cramps.
AB  - This study in humans tested the hypothesis that nociceptive muscle afferent input
      facilitates the occurrence of muscle cramps. In 13 healthy adults, muscle cramps
      were experimentally induced in the foot by stimulating the tibialis posterior
      nerve at the ankle with 2-s bursts of stimuli separated by 30 s, with stimulation
      frequency increasing by 2-Hz increments from 10 Hz until the cramp appeared. The
      minimum stimulation frequency that induced the cramp was defined "cramp frequency
      threshold". In 2 days, elicitation of the cramp was performed in the two-feet
      with and without (baseline condition) injection of hypertonic (painful condition)
      or isotonic (control condition) saline into the deep midportion of the flexor
      hallucis brevis muscle, from where surface EMG signals were recorded. The cramp
      frequency threshold was lower for the painful condition with respect to its
      baseline (mean +/- SE, hypertonic saline: 25.7 +/- 2.1 Hz, corresponding
      baseline: 31.2 +/- 2.8 Hz; P < 0.01) while there was no difference between the
      threshold with isotonic injection with respect to baseline. EMG average rectified
      value and power spectral frequency were higher during the cramp than immediately
      before the stimulation that elicited the cramp (pre-cramp: 13.9 +/- 1.6 muV and
      75.4 +/- 3.8 Hz, respectively; post-cramp: 19.9 +/- 3.2 muV and 101.6 +/- 6.0 Hz;
      P < 0.05). The results suggest that nociceptive muscle afferent activity induced
      by injection of hypertonic saline facilitates the generation of electrically
      elicited muscle cramps.

PMID- 17551720
TI  - Comparing limb proprioception and oculomotor signals during hand-guided saccades.
AB  - We previously showed that saccades tend to overshoot briefly flashed targets that
      were manually displaced in the dark (Ren et al. 2006). However it was not clear
      if the overshoot originated from a sensory error in measuring hand displacement
      or from a premotor error in saccade programming, because gaze and hand position
      started at the same central position. Here, we tested between these hypotheses by
      dissociating the initial eye and hand position. Five hand/target positions
      (center, far, near, right, left) on a frontally-placed horizontal surface were
      used in four paradigms: Center or Peripheral Eye-hand Association (CA or PA, both
      gaze and right hand started from the center or a same peripheral location) and
      Hand or Eye Dissociation (HD or ED, hand or gaze started from one of three non
      target peripheral locations). Subjects never received any visual feedback about
      the final target location and the subjects' hand displacement. In the CA
      paradigm, subjects showed the same overshoot that we showed previously. However,
      changing both initial eye and hand positions relative to the final target (PA)
      affected the pattern, significantly altering the directions of overshoots.
      Changing only the initial position of hand (HD) did not have this effect, whereas
      changing only initial eye position (ED) had the same effect as the PA condition
      (CA approximately HD, PA approximately ED). Furthermore, multiple regression
      analysis showed that the direction of the ideal saccade contributed significantly
      to the endpoint direction error, not the direction of the hand path. These
      results suggest that these errors do not primarily arise from misestimates of the
      hand trajectory, but rather from a process of comparing the initial eye position
      and the limb proprioceptive signal during saccade programming.

PMID- 17551721
TI  - Sagittal synostosis in X-linked hypophosphatemic rickets and related diseases.
AB  - BACKGROUND: The recent observations of two new cases of X-linked hypophosphatemic
      rickets associated with premature closure of the sagittal suture prompted a
      review of similar cases seen in this institution. OBJECTIVES: To review the
      clinical records and skull radiographs of 28 children with hypophosphatemic
      rickets in order to investigate the frequency and type of craniosynostosis and
      other cranial vault changes seen in these conditions and to review the literature
      for relevant findings. MATERIALS AND METHODS: Clinical and imaging records were
      reviewed on 28 patients with hypophosphatemic rickets, all younger than 18 years.
      Most patients had X-linked hypophosphatemic rickets and a few had autosomal
      dominant hypophosphatemic rickets or were non-familial cases. RESULTS: Of the 28
      patients, 13 had sagittal synostosis. Dolichocephaly was present in ten patients.
      The configuration of the cranial vault in some of these ten patients with
      dolichocephaly varied somewhat from that seen in nonsyndromic sagittal
      synostosis. In one patient, a Chiari I malformation was demonstrated by MRI. In
      another patient with increased intracranial pressure the sagittal suture closure
      was associated with lambdoidal synostosis. Dolichocephaly was not present in
      three patients, suggesting that the synostosis started later than in the other
      patients, probably in the second year of life, a period of slower brain growth
      than in the first year. The two patients in this group of three showed thickening
      and sclerosis of the cranial vault of uncertain etiology. CONCLUSION: There is an
      increased risk of sagittal synostosis in hypophosphatemic rickets and related
      diseases in children. The appearance of the cranial vault in this type of
      synostosis can vary from that seen in nonsyndromic synostosis. In this setting,
      careful clinical and imaging follow-up is warranted.

PMID- 17551722
TI  - Outer membrane proteins: comparing X-ray and NMR structures by MD simulations in
      lipid bilayers.
AB  - The structures of three bacterial outer membrane proteins (OmpA, OmpX and PagP)
      have been determined by both X-ray diffraction and NMR. We have used multiple (7
      x 15 ns) MD simulations to compare the conformational dynamics resulting from the
      X-ray versus the NMR structures, each protein being simulated in a lipid (DMPC)
      bilayer. Conformational drift was assessed via calculation of the root mean
      square deviation as a function of time. On this basis the 'quality' of the
      starting structure seems mainly to influence the simulation stability of the
      transmembrane beta-barrel domain. Root mean square fluctuations were used to
      compare simulation mobility as a function of residue number. The resultant
      residue mobility profiles were qualitatively similar for the corresponding X-ray
      and NMR structure-based simulations. However, all three proteins were generally
      more mobile in the NMR-based than in the X-ray simulations. Principal components
      analysis was used to identify the dominant motions within each simulation. The
      first two eigenvectors (which account for >50% of the protein motion) reveal that
      such motions are concentrated in the extracellular loops and, in the case of
      PagP, in the N-terminal alpha-helix. Residue profiles of the magnitude of motions
      corresponding to the first two eigenvectors are similar for the corresponding X
      ray and NMR simulations, but the directions of these motions correlate poorly
      reflecting incomplete sampling on a approximately 10 ns timescale.

PMID- 17551723
TI  - Amazonian Amerindians exhibit high variability of KIR profiles.
AB  - Natural killer cell immunoglobulin-like receptors (KIRs) mediate cell lysis
      through the recognition of human leukocyte antigen class I complexes in target
      cells, playing an important role in innate immune response. In this context,
      disease-based selective pressures could be relevant, leaving signatures detected
      by population studies. However, most population studies on KIR variability have
      focused on Europe and Asia, while Americas, Oceania, and Africa remain poorly
      studied. The aim of this study was to analyze the variability of KIR genes in
      Amerindian tribes from the Amazon region to infer about their evolutionary
      history. KIR profiles were estimated in 40 individuals from six Amazonian
      Amerindian tribes using single specific primer polymerase chain reaction. Twenty
      five different profiles were identified, and surprisingly, the haplogroup A
      frequency was the lowest observed in human populations (16%). Results showed also
      that KIR variability was higher in this group in contrast to Venezuelan
      Amerindians. Principal components analysis evidenced that Amerindians formed a
      separated group from other worldwide populations and showed a higher intraethnic
      differentiation in comparison to other ethnic groups. Such pattern may reflect
      small effective size and intense genetic drift. However, because of the role of
      KIR in immune response, selective pressures cannot be entirely ruled out.

PMID- 17551724
TI  - Cardiovascular molecular imaging of apoptosis.
AB  - INTRODUCTION: Molecular imaging strives to visualise processes at the molecular
      and cellular level in vivo. Understanding these processes supports diagnosis and
      evaluation of therapeutic efficacy on an individual basis and thereby makes
      personalised medicine possible. APOPTOSIS AND MOLECULAR IMAGING: Apoptosis is a
      well-organised mode of cell suicide that plays a role in cardiovascular diseases
      (CVD). Apoptosis is associated with loss of cardiomyocytes following myocardial
      infarction, atherosclerotic plaque instability, congestive heart failure and
      allograft rejection of the transplanted heart. Thus, apoptosis constitutes an
      attractive target for molecular imaging of CVD. Our current knowledge about the
      molecular players and mechanisms underlying apoptosis offers a rich palette of
      potential molecular targets for molecular imaging. However, only a few have been
      successfully developed so far. AIMS: This review highlights aspects of the
      molecular machinery and biochemistry of apoptosis relevant to the development of
      molecular imaging probes. It surveys the role of apoptosis in four major areas of
      CVD and portrays the importance and future perspectives of apoptosis imaging. The
      annexin A5 imaging protocol is emphasised since it is the most advanced protocol
      to measure apoptosis in both preclinical and clinical studies.

PMID- 17551725
TI  - Proprioceptive skills and functional outcome after anterior cruciate ligament
      reconstruction with a bone-tendon-bone graft.
AB  - Several studies have shown that patients with anterior cruciate ligament (ACL)
      reconstruction have an improved proprioceptive function compared to subjects with
      ACL-deficient knees. The measurement of functional scores and proprioception
      potentially provides clinicians with more information on the status of the ACL
      reconstructed knees. To evaluate proprioception in patients following ACL
      reconstruction with a bone-tendon-bone (BTB) graft, we used the angle
      reproduction in the sitting, lying and standing positions and the one-leg hop
      test. Forty-five patients between 19 and 52 years of age were investigated in a
      36-month period after the operation. For functional performance measurement, the
      International Knee Documentation Committee (IKDC) score was used. Very good and
      good results were seen in 95% of cases. All patients returned to the same
      activity level as seen before ACL repair. There was a significant difference in
      the active angle reproduction test between the ACL-reconstructed knees and normal
      knees in the active sitting position. Tests with passive angle adjustment in the
      sitting, lying and active standing positions did not show any differences in
      proprioceptive skills. Good to very good results in the one-leg hop test we found
      in 95% of patients. After ACL reconstruction, deficiencies in the active angle
      reproduction test were very small but, nevertheless, were still observed.
      Overall, the functional and proprioceptive outcomes demonstrate results to
      recommend the procedure.

PMID- 17551726
TI  - Resistant tennis elbow: shock-wave therapy versus percutaneous tenotomy.
AB  - Fifty-six patients who suffered from chronic persistent tennis elbow of more than
      six months duration were randomly assigned to two active treatment groups. Group
      1 (n = 29) received high-energy extracorporeal shock wave treatment (ESWT; 1,500
      shocks) at 18 kV (0.22 mJ/mm(2)) without local anaesthesia; group 2 (n = 27)
      underwent percutaneous tenotomy of the common extensor origin. Both groups
      achieved improvement from the base line at three weeks, six weeks, 12 weeks and
      12 months post-intervention. The success rate (Roles and Maudsley score:
      excellent and good) at three months in the ESWT group was 65.5% and in the
      tenotomy group was 74.1%. ESWT appeared to be a useful noninvasive treatment
      method that reduced the necessity for surgical procedures.

PMID- 17551727
TI  - [The grading of invasive breast cancer according to Elston and Ellis].

PMID- 17551728
TI  - Native and modified lactate dehydrogenase expression in a fumaric acid producing
      isolate Rhizopus oryzae 99-880.
AB  - Rhizopus oryzae is subdivided into two groups based on genetic and phenotypic
      differences. Type-I isolates accumulate primarily lactic acid when grown in the
      presence of a fermentable carbon source and contain two lactate dehydrogenase
      genes, ldhA and ldhB. Type-II isolates synthesize predominantly fumaric acid and
      only have an ldhB gene. In this study, we determined that ldhB transcript is only
      minimally expressed in the Type-II isolate R. oryzae 99-880. LdhB enzyme purified
      from gene clones isolated from the Type-I isolate R. oryzae NRRL 395 and the Type
      II isolate R. oryzae 99-880 each showed reductive LDH activity (pyruvate to
      lactate), while no oxidative LDH activity (lactate to pyruvate) was detected in
      either preparation. A transformation system was then developed for the first time
      with R. oryzae 99-880, using a uracil auxotrophic isolate that could be
      complemented with an orotate phosphoribosyltransferase gene, pyrF, isolated in
      this study. Transformation of this Type-II isolate with the ldhA gene from R.
      oryzae NRRL 395 resulted in reductive LDH activity between 1.0 and 1.8 U/mg total
      protein. Additionally, transformed isolates grown with glucose accumulated up to
      27 g lactic acid/l with a concurrent decrease in fumaric acid, ethanol, and
      glycerol compared with the untransformed and vector-transformed control strains.

PMID- 17551729
TI  - Establishment of an efficient Agrobacterium tumefaciens-mediated leaf disc
      transformation of Thellungiella halophila.
AB  - Thellungiella halophila is a salt-tolerant close relative of Arabidopsis, which
      is adopted as a halophytic model for stress tolerance research. We established an
      Agrobacterium tumefaciens-mediated transformation procedure for T. halophila.
      Leaf explants of T. halophila were incubated with A. tumefaciens strain EHA105
      containing a binary vector pCAMBIA1301 with the hpt gene as a selectable marker
      for hygromycin resistance and an intron-containing beta-glucuronidase gene as a
      reporter gene. Following co-cultivation, leaf explants were cultured on selective
      medium containing 10 mg l(-1) hygromycin and 500 mg l(-1) cefotaxime. Hygromycin
      resistant calluses were induced from the leaf explants after 3 weeks. Shoot
      regeneration was achieved after transferring the calluses onto fresh medium of
      the same composition. Finally, the shoots were rooted on half strength MS basal
      medium supplemented with 10 mg l(-1) hygromycin. Incorporation and expression of
      the transgenes were confirmed by PCR, Southern blot analysis and GUS
      histochemical assay. Using this protocol, transgenic T. halophila plants can be
      obtained in approximately 2 months with a high transformation frequency of 26%.

PMID- 17551731
TI  - Highly efficient Agrobacterium-mediated transformation of embryogenic cell
      suspensions of Musa acuminata cv. Mas (AA) via a liquid co-cultivation system.
AB  - A high efficient protocol of Agrobacterium-mediated transformation of Musa
      acuminata cv. Mas (AA), a major banana variety of the South East Asia region, was
      developed in this study. Male-flower-derived embryogenic cell suspensions (ECS)
      were co-cultivated in liquid medium with Agrobacterium strain EHA105 harboring a
      binary vector pCAMBIA2301 carrying nptII and gusA gene in the T-DNA. Depending
      upon conditions and duration of co-cultivation in liquid medium, 0-490 transgenic
      plants per 0.5 ml packed cell volume (PCV) of ECS were obtained. The optimum
      duration of inoculation was 2 h, and the highest transformation frequency was
      achieved when infected ECS were co-cultivated in liquid medium first for 12 h at
      40 rpm and then for 156 h at 100 rpm on a rotary shaker. Co-cultivation for a
      shorter duration (72 h) or shaking constantly at 100 rpm at the same duration
      gave 1.6 and 1.8 folds lower transformation efficiency, respectively. No
      transgenic plants were obtained in parallel experiments carried on semi-solid
      media. Histochemical GUS assay and molecular analysis in several tissues of the
      transgenic plants demonstrated that foreign genes were stably integrated into the
      banana genome. Compared to semi-solid co-cultivation transformation in other
      banana species, it is remarkable that liquid co-cultivation was much more
      efficient for transformation of the Mas cultivar, and was at least 1 month faster
      for regenerating transgenic plants.

PMID- 17551730
TI  - Post-Golgi protein traffic in the plant secretory pathway.
AB  - The Golgi apparatus in plants is organized as a multitude of individual stacks
      that are motile in the cytoplasm and in close association with the endoplasmic
      reticulum (ER) (Boevink et al. in Plant J 15:441-447, 1998). These stacks operate
      as a sorting centre for cargo molecules, providing modification and redirection
      to other organelles as appropriate. In the post-Golgi direction, these include
      vacuole and plasma membrane, and specialized transport routes to each are
      required to prevent mislocalization. Recent evidence in plant cells points to the
      existence of post-Golgi organelles that function as intermediate stations for
      efficient protein traffic, as well as to the influence of small GTPases such as
      Rabs and ARFs on post-Golgi trafficking. This review focuses on the latest
      findings on post-Golgi trafficking routes and on the involvement of GTPases and
      their effectors on the trafficking of proteins in the plant secretory pathway.

PMID- 17551732
TI  - [Wavefront aberrations and subjective quality of vision after wavefront-guided
      LASIK: first results].
AB  - PURPOSE: To investigate the clinical impact of the postoperative ocular wavefront
      error (WFE) on subjective quality of vision (SQV) after LASIK. METHOD: Forty-one
      myopic eyes of 21 patients underwent uneventful LASIK (median -4.63 D).
      Preoperatively and 1 month postoperatively, WFE measurements were performed and
      overall SQV was assessed for two lighting conditions (photopic and mesopic) with
      a questionnaire. Three different WFE representations were computed for a pupil
      diameter of 6 mm: (1) the visual quality metric VSOTF (visual Strehl ratio based
      on the optical transfer function), (2) RMS (root mean square) values of the
      Zernike orders 2-5, and (3) individual Zernike coefficient for orders 2-5. The
      impact of the postoperative WFE on SQV was calculated using linear regression
      analysis. RESULTS: For photopic conditions R(2) was 0.24 for model 1 (VSOTF),
      0.31 for model 2 (RMS values), and 0.29 for model 3 (Zernike coefficients).
      Second-and fifth-order aberrations had significant influence on SQV. For mesopic
      conditions, results were similar. CONCLUSION: Subjective quality of vision after
      wavefront-guided LASIK could be explained partially by the ocular WFE.

PMID- 17551733
TI  - [A new posterior chamber intraocular lens for sutureless iris-fixated ciliary
      sulcus implantation in aphakic eyes without capsular support].
AB  - PURPOSE: To avoid anterior chamber lens implantation in aphakic eyes without
      capsular or zonular support, the laborious scleral fixation of a standard
      posterior chamber intraocular lens (IOL) is widely used, despite a large range of
      possible complications (macular edema, IOL tilt/decentration, suture erosion,
      vitreous hemorrhage). A sutureless iris-fixed ciliary sulcus implantation of a
      posterior chamber IOL (Binder-IOL, Fa. Iolution, Itzehoe) designed especially for
      such cases represents an alternative. METHOD: At the end of both haptics of this
      IOL, with a 6 mm optic zone, a T-shaped anchor is mounted at an angle of 45
      degrees from the optical plane. These anchors are inserted from behind the iris
      into peripheral iridotomies performed preoperatively with a YAG-laser or
      intraoperatively with a vitrectomy cutter. The long, C-shaped haptics are thus
      secured in the ciliary sulcus. RESULTS: After slight modification of the
      technique, the implantation can be performed securely and reproducibly. In the 22
      implantations performed to date, the IOL was well centered and stable, even in
      cases with only residual iris stroma. If the iridotomies are been performed too
      centrally, an ovalisation of the pupil may occur. No further side effects have
      been observed. CONCLUSION: The technique of sutureless sulcus fixation presented
      here leads to less complications than scleral suture fixation. A prerequisite for
      safe implantation of the anchors is good visibility of the peripheral iris. The
      implantation of the Binder-IOL is especially suitable for aphakic eyes with a
      loosened iris diaphragm.

PMID- 17551734
TI  - Reinforcement pre-exposure enhances spatial memory formation in Drosophila.
AB  - Apparently unpaired exposure to appetitive or aversive stimuli can suppress or
      enhance later associative learning. While the suppressive effect has been found
      in both vertebrate and invertebrate animals, it is not clear if the enhancing
      effect is restricted to the vertebrates. Additionally, whether Drosophila
      associative learning can be influenced in either direction is open. To address
      these questions, we examined the effects of pre-exposing flies to a high
      temperature negative reinforcer in the heat-box place-learning paradigm. We found
      that pre-exposing flies to an unavoidable high temperature enhanced later
      associative conditioning that uses mild increases in temperature. This
      enhancement lasts at least 20 min, does not depend on changes in the
      straightforward avoidance behavior of a high temperature source, and is
      independent of the antennal thermosensor. We thus provide an example of enhanced
      associative learning after unpaired exposure to a typical reinforcer in an
      invertebrate animal, suggesting the conservation of this component of learning.

PMID- 17551735
TI  - Dynamic properties of large-field and small-field optomotor flight responses in
      Drosophila.
AB  - Optomotor flight control in houseflies shows bandwidth fractionation such that
      steering responses to an oscillating large-field rotating panorama peak at low
      frequency, whereas responses to small-field objects peak at high frequency. In
      fruit flies, steady-state large-field translation generates steering responses
      that are three times larger than large-field rotation. Here, we examine the
      optomotor steering reactions to dynamically oscillating visual stimuli consisting
      of large-field rotation, large-field expansion, and small-field motion. The
      results show that, like in larger flies, large-field optomotor steering responses
      peak at low frequency, whereas small-field responses persist under high frequency
      conditions. However, in fruit flies large-field expansion elicits higher
      magnitude and tighter phase-locked optomotor responses than rotation throughout
      the frequency spectrum, which may suggest a further segregation within the large
      field pathway. An analysis of wing beat frequency and amplitude reveals that
      mechanical power output during flight varies according to the spatial
      organization and motion dynamics of the visual scene. These results suggest that,
      like in larger flies, the optomotor control system is organized into parallel
      large-field and small-field pathways, and extends previous analyses to quantify
      expansion-sensitivity for steering reflexes and flight power output across the
      frequency spectrum.

PMID- 17551736
TI  - Inhibition of nitric oxide and soluble guanylyl cyclase signaling affects
      olfactory neuron activity in the moth, Manduca sexta.
AB  - Nitric oxide is emerging as an important modulator of many physiological
      processes including olfaction, yet the function of this gas in the processing of
      olfactory information remains poorly understood. In the antennal lobe of the
      moth, Manduca sexta, nitric oxide is produced in response to odor stimulation,
      and many interneurons express soluble guanylyl cyclase, a well-characterized
      nitric oxide target. We used intracellular recording and staining coupled with
      pharmacological manipulation of nitric oxide and soluble guanylyl cyclase to test
      the hypothesis that nitric oxide modulates odor responsiveness in olfactory
      interneurons through soluble guanylyl cyclase-dependent pathways. Nitric oxide
      synthase inhibition resulted in pronounced effects on the resting level of firing
      and the responses to odor stimulation in most interneurons. Effects ranged from
      bursting to strong attenuation of activity and were often accompanied by membrane
      depolarization coupled with a change in input resistance. Blocking nitric oxide
      activation of soluble guanylyl cyclase signaling mimicked the effects of nitric
      oxide synthase inhibitors in a subset of olfactory neurons, while other cells
      were differentially affected by this treatment. Together, these results suggest
      that nitric oxide is required for proper olfactory function, and likely acts
      through soluble guanylyl cyclase-dependent and -independent mechanisms in
      different subsets of neurons.

PMID- 17551737
TI  - Successful embolization of a giant perimedullary arteriovenous fistula of the
      cervical spine in a 6-year-old child.
AB  - CASE: We report a case of a 6-year-old boy with a giant perimedullary
      arteriovenous fistula of the cervical spine who presented with progressive
      tetraparesis. METHOD: Transarterial glue embolization was performed and complete
      occlusion of the fistula was achieved. RESULT: The patient's symptoms resolved
      completely during the next year.

PMID- 17551738
TI  - Deep brain stimulation for torsion dystonia in children.
AB  - INTRODUCTION: Deep brain stimulation (DBS) at the internal globus pallidus (GPi)
      is an effective treatment for some patients with medically refractory torsion
      dystonia. In this article, we review the results of pallidal DBS surgery in
      children with dystonia. Details of the DBS procedure and programming of the DBS
      devices are discussed. DISCUSSION: Pallidal DBS is most effective in patients
      with primary generalized dystonia. Children and adolescents possessing the DYT1
      gene mutation may respond best of all. The presence of static dystonic postures
      and/or fixed orthopedic contractures may limit the functional response to DBS and
      may require additional surgery. CONCLUSION: As a group, patients with secondary
      dystonias respond less well to DBS than patients with primary dystonia. However,
      patients with dystonia secondary to anoxic brain injury who have grossly intact
      basal ganglia anatomy may represent a subpopulation for whom pallidal DBS is a
      viable option.

PMID- 17551739
TI  - Selective dorsal rhizotomy for spastic cerebral palsy: a review.
AB  - OBJECTIVE: The purpose of this report is to review the historical development,
      current operative techniques, selection criteria, outcomes, and complications of
      selective dorsal rhizotomy (SDR) for treatment of spastic cerebral palsy (CP).
      MATERIALS AND METHODS: This review is based on a review of literature and
      personal observations. RESULTS: SDR has evolved from the 1960s onwards into a
      standard neurosurgical procedure for spastic CP. There is much variation in the
      operative technique among surgeons with respect to the level of exposure,
      electrophysiological guidance, and extent of rhizotomies. Appropriate selection
      of patients for SDR requires determination that spasticity, not dystonia, is the
      major disabling hypertonia and that the lower limbs are maximally involved.
      Positive outcomes have been well demonstrated in the impairment, functional
      limitations, and disability dimensions, as per the National Center for Medical
      Rehabilitation Research Model of Dimensions of the Disabling Process.
      Complications have been relatively few. CONCLUSIONS: SDR is the procedure of
      choice for treatment of spasticity in spastic diplegic CP and in selected
      children with spastic quadriplegic CP. Optimal selection and outcomes are
      achieved using a multidisciplinary approach.

PMID- 17551740
TI  - A case of congenital kyphosis misdiagnosed as cerebral palsy.
AB  - INTRODUCTION: Congenital kyphosis is an uncommon spinal deformity that needs
      prompt recognition and early surgery due to its progressive nature, which can
      lead to neurological compromise. CASE REPORT: An 11-year-old boy presented with
      deteriorating ambulatory function after bilateral Achilles tendon lengthening and
      calcaneal osteotomies. He previously had a series of orthopedic surgeries of the
      lower extremities, having been diagnosed with spastic diplegic cerebral palsy
      based on clinical features and history of prematurity. His computed tomography
      (CT) scan and magnetic resonance imaging (MRI) revealed compressive thoracic
      myelopathy due to the fusion of vertebral bodies from T2 to T5. He was treated
      with anterior decompression and anteroposterior fusion of the thoracic spine.
      DISCUSSION: Neurological impairment such as spastic paraplegia in children can
      lead to an erroneous diagnosis of cerebral palsy, resulting in unnecessary
      surgeries with their attendant potential complications. This report alerts
      clinicians to the presentation and progression of congenital vertebral anomalies
      and highlights the importance of a thorough neurological examination and
      radiological evaluation.

PMID- 17551741
TI  - Tight filum terminale syndrome in children: analysis based on positioning of the
      conus and absence or presence of lumbosacral lipoma.
AB  - BACKGROUND: Tight filum terminale syndrome (TFTS) characterized by findings
      consistent with a tethered cord but with the conus ending in a normal position
      has only recently been observed in children. In this situation, diagnosis may
      prove difficult and sectioning of the filum terminale is questionable. MATERIALS
      AND METHODS: Sixty cases of pediatric TFTS were analyzed by methods including
      spinal X-ray and magnetic resonance imaging (MRI). Twenty-one patients exhibited
      a normally positioned conus, 18 a low-lying conus, and 21 a low-lying conus with
      accompanying lumbosacral lipoma. These three groups were compared preoperatively
      and postoperatively for lumbosacral cutaneous stigmata, vertebral anomalies,
      concomitant congenital spinal dysraphisms, lower limb deformities, and sphincter
      dysfunction. RESULTS: Rates of occurrence of lumbosacral cutaneous stigmata and
      other concomitant congenital spinal dysraphisms differed significantly among the
      groups. Differences in other parameters were not observed. All groups responded
      positively to surgery. CONCLUSIONS: Pediatric TFTS may involve a normally
      positioned conus. Diagnosis of pediatric TFTS should be based on clinical
      presentation, physical and radiological examinations, MRI, and pathologic changes
      in the filum. When neurological signs accompany such changes, early severing of
      the filum is indicated regardless of conus position.

PMID- 17551742
TI  - Surgical treatment of myelomeningocele: year 2000 hospitalization, outcome, and
      cost analysis in the US.
AB  - OBJECTIVE: To review cases of surgical repair for myelomeningocele (MMC) using a
      large inpatient database from the year 2000. MATERIALS AND METHODS: The
      Nationwide Inpatient Sample (NIS) database with 7.45 million patient admissions
      for 2000 was retrospectively studied for the first 5 procedure diagnosis of MMC
      repair (ICD-9 CM procedure code 0352) and ages of less than 1 year. Eighty-eight
      patient stays were identified. Patient demographic data, length of stay,
      immediate disposition at the time of discharge, hospital information, and total
      cost for the hospitalization were determined. CONCLUSION: Myelomeningocele repair
      is mostly performed in large teaching institutions in small numbers. The majority
      gets to go home at discharge. It is surprising to note that only 35% also
      required VP shunt placement during the same hospitalization.

PMID- 17551743
TI  - Long-term outcome of infants with positional occipital plagiocephaly.
AB  - BACKGROUND: Despite much interest in positional (deformational) plagiocephaly,
      the natural history is unclear. The purpose of this study was to determine
      cosmetic and developmental outcomes at a minimum of 5 years of age in children
      diagnosed in infancy with positional plagiocephaly (PP) and the impact of cranial
      orthotic use. METHODS: A questionnaire survey was sent to parents of children
      diagnosed with PP in infancy and now aged more than 5 years. A retrospective
      review of the child's clinic chart was performed of consenting families, and
      prospective follow-up was done when families agreed to return for assessment.
      RESULTS: Of 278 eligible children with plagiocephaly, questionnaires were
      completed by 65 parents, and 27 brought their child for assessment. Participants
      and nonparticipants were similar. Cranial orthoses were used in 18 of 65
      children. Parents perceived the cosmetic appearance of their child as "very
      abnormal" in 2, "mildly abnormal" in 25, and "normal" in 38. Residual asymmetry
      was noted by parents in 58%, but only 21% were concerned about appearance. In the
      last year, 7.7% of children commented about asymmetry of head, and 4.6% were
      teased occasionally. Thirty-three percent had received learning assistance, and
      14% were in a special class. Long-term outcomes, as perceived by the parent or
      child, were no different between children with and without orthosis use.
      CONCLUSIONS: The results allow better counselling of parents about outcome of
      infants with PP, reducing anxiety, and allowing more rational selection of
      management modality.

PMID- 17551744
TI  - The blind colonic J-pouch: an original technique to reduce the surgical risk in
      the treatment of extra-peritoneal rectal cancer.
AB  - BACKGROUND: Low and ultra-low anterior resection with colo-rectal or colo-anal
      anastomosis is accompanied by high frequency of postoperative anastomotic
      leakage. The aim of this report is to describe a novel technical approach to
      colorectal reconstruction. MATERIALS AND METHODS: The innovative procedure
      introduces the principle of 'no anastomosis-no leakage', and it can be performed
      both laparascopically or by means of a laparotomy. It consists of a simple colo
      rectal or colo-anal apposition with latero-terminal modality, with the creation
      of a colonic J-pouch called "blind" because it remains closed in the external
      site and the anus is sealed up. The surgery is completed with an exclusive
      derivative colostomy, and the reconstruction of the intestinal continuity is
      postponed to a second operation. Within 4-6 weeks from the first, the blind pouch
      is opened, the communication between the anus and the colon is established, and
      the colostomy is closed and reduced in the peritoneal cavity. RESULTS AND
      CONCLUSIONS: Ethics committee of our hospital approved the experimental program;
      actually, we are finishing the first step on 15 patients, and preliminary
      clinical results look like to be very good. The innovative methodology is here
      described in advance, and we pledge to spread clinical results in a subsequent
      report.

PMID- 17551745
TI  - Morbidity associated with posterior intravaginal slingplasty for uterovaginal and
      vault prolapse.
AB  - OBJECTIVE: This study was carried out to evaluate the safety and efficacy of
      posterior intravaginal slingplasty (IVS) for upper genital prolapse. SETTING:
      Gynaecology Department, Benenden Hospital, Kent, UK. MATERIALS AND METHODS: An
      observational study was conducted on 127 women, who underwent posterior IVS using
      the IVS Tunneller (Tyco HealthCare, USS, Norwalk, CT, USA). The indications for
      surgery were uterovaginal prolapse in 65% and vault prolapse in 35%. Patient
      follow-up was at 6 weeks, 6 months, 1 year and annually thereafter. RESULTS: In
      addition to posterior IVS, hysterectomy was performed in 22 patients, anterior
      colporrhaphy in 63 patients and transobturator mid-urethral tape insertion in
      eight patients. The mean operating time was 46 +/- 18.5 min and for posterior IVS
      alone was 27.4 +/- 10 min, and the mean peri-operative drop in haemoglobin level
      was 1.4 +/- 0.75 gm/dL. There were no rectal, vesical or ureteric injuries. After
      a mean follow-up of 14 months (range 2-26 months), upper genital support was
      maintained in 88%, cystocele formation occurred in 8% and recurrent rectocele was
      seen in 11%. There was a 17% risk of tape erosion (21/127) and a re-operation
      rate of 24% (30/127). The risk of tape erosion was related to patient age above
      60 years (RR = 1.6, 95% CI 1.02-2.5) and current treatment for diabetes (RR = 4,
      95% CI 1.7-9.2). Parity, body mass index, menopausal status, HRT use,
      hysterectomy and surgeon's experience were not found to influence tape erosion
      rate. CONCLUSION: Posterior intravaginal slingplasty is a minimally invasive
      procedure for upper genital prolapse with an acceptable success rate. However,
      the operation is associated with high vaginal erosion and re-operation rates.

PMID- 17551746
TI  - Expression of the novel protein PTPIP51 in rat liver: an immunohistochemical
      study.
AB  - Expression of the novel protein tyrosine phosphatase interacting protein 51
      (PTPIP51) was investigated on mRNA and protein level in the liver of adult Wistar
      rats. The presence of PTPIP51 mRNA was detected by Northern blotting.
      Immunostaining showed expression of PTPIP51 protein in distinct non-parenchymal
      cells. These cells were identified as Kupffer cells, stellate cells and natural
      killer cells by detection of cell-specific antigens. Whereas most endothelial
      cells lining large vessels reacted positive to the PTPIP51 antibody, sinusoidal
      endothelium showed no detectable amount of PTPIP51. Furthermore, PTPIP51 was also
      found to be expressed in cells forming the biliary tree. An additional
      subcellular analysis of the non-parenchymal cells by means of electron microscopy
      showed the presence of PTPIP51 protein in the cytoplasm and in the nuclei of non
      parenchymal cells. Most of the hepatocytes did not show any immuno-detectable
      amount of PTPIP51, yet, some revealed PTPIP51 protein either in the cytoplasm or
      in the nucleus.

PMID- 17551747
TI  - Expression of the blood-group-related antigens Sialyl Lewis a, Sialyl Lewis x and
      Lewis y in term placentas of normal, preeclampsia, IUGR- and HELLP-complicated
      pregnancies.
AB  - Lewis antigens belong to the blood group of antigens and mediate cellular
      adhesion through interaction with selectins. Invasive trophoblasts use an array
      of adhesion molecules to facilitate cell-cell and cell-extracellular matrix
      interactions. Here, we examined immunohistochemically the expression of Sialyl
      Lewis a (sLe(a)), Sialyl Lewis x (sLe(x)) and Lewis y (Le(y)) in term placentas
      obtained from cases of normal, intrauterine growth retardation (IUGR),
      preeclamptic (PE) and hemolysis, elevated liver enzymes and low platelets
      syndrome (HELLP) pregnancies. We report the expression of sLe(x) in third
      trimester extravillous trophoblasts (EVT). sLe(x) was significantly decreased in
      IUGR and moderately decreased in PE compared to normal placentas. sLe(x) was
      additionally found in syncytiotrophoblast, without however any significant
      differences in staining intensity between normal and pathological cases. sLe(a)
      was restricted to amnion epithelium. Finally, Le(y) was expressed in
      cytotrophoblasts and villous endothelial cells. Le(y) expression was
      significantly upregulated in IUGR and HELLP, whereas there was a trend toward
      increase in PE compared to normal placentas. The present study suggests that
      downregulation of sLe(x) in EVT might be associated with IUGR and PE.
      Furthermore, Le(y), which was recently described as a potent angiogenic factor,
      is upregulated in placental villi in conditions associated with placental
      malperfusion.

PMID- 17551748
TI  - Identification and subcellular localization of paracellin-1 (claudin-16) in human
      salivary glands.
AB  - Salivary calcium plays an important role in the pathogenesis of dental caries and
      the bio-mineralization of dental enamel and exposed dentin. The cellular and
      molecular basis of calcium secretion by the human salivary glands is, however,
      poorly understood. Recently a transcellular transport of calcium by the acinus
      cells has been proposed. In this paper we looked for evidence for paracellular
      calcium transport by investigating the presence and cellular localization of
      paracellin-1 (claudin-16) that has been implied in paracellular magnesium and
      calcium transport in the kidney. At the mRNA level, using RT-PCR with primers of
      appropriate sequence, paracellin-1 mRNA could be found in human Glandula parotis,
      Glandula submandibularis, Glandula labialis and Glandula sublingualis samples. In
      addition, a splice variant was detected in three out of 15 glands consisting of
      exons one and five of the paracellin gene. In immunohistochemical studies
      paracellin-1 colocalised in the salivary excretory ducts with the tight junction
      proteins ZO-1 and occludin suggesting a potential role in paracellular calcium
      and magnesium transport. In the acini no such colocalisation was observed;
      paracellin was instead detected at the basal poles of the cells, between cells of
      the same acinus as well as between cells of neighboring acini. At this location
      paracellin-1 might act as selectivity filter for the paracellular movement of
      ions and water during stimulated secretion. Thus, both in the ducts and in the
      acini a paracellular transport of calcium appears possible. Whether it occurs at
      all and the extent to which it contributes to the overall salivary calcium
      secretion remains, however, to be determined.

PMID- 17551749
TI  - Evidence of sex-based differences in natural killer cell responses to exercise
      and carbohydrate intake in children.
AB  - Distinct natural killer (NK) cell subsets (CD56bright and CD56dim) are mobilized
      with exercise and these cells may serve adaptive functions. We determined the
      distribution of NK cell subsets in response to exercise and carbohydrate (CHO)
      intake in young girls and compared these responses with previous findings in
      young boys of the same age. Twelve girls (12 years old) cycled for 60 min at 70%
      VO2max while drinking 6% CHO or flavoured water. Blood was collected at rest,
      during (30 and 60 min) and following (30 and 60 min) exercise to identify NK
      cells as CD3-CD56bright or CD3-CD56dim. CD69 expression on total CD3-CD56+ cells
      was also determined. A trend (P=0.07) was found for a trial x time interaction in
      CD56dim cell counts, with values lower with CHO than with water. CHO intake did
      not influence CD56bright responses (P>or=0.39). The CD56bright:CD56dim ratio
      increased during recovery from exercise (P<0.001), compared to rest, with no
      effect of CHO intake (P=0.48). CD69 expression was not different between exercise
      or recovery and rest. Like young boys, girls experience an elevated
      CD56bright:CD56dim ratio during recovery from exercise and CHO intake attenuates
      the exercise-induced CD56dim but not CD56bright cell response. Unlike young boys,
      girls do not experience a CHO-induced increase in the CD56bright:CD56dim ratio
      during recovery and CD69 expression does not increase on CD3-CD56+ cells during
      recovery. We conclude that even in young children sex-based differences exist in
      the NK cell response to exercise and CHO intake.

PMID- 17551750
TI  - Passive force enhancement in single myofibrils.
AB  - The purpose of this study was to gain further insight into passive force
      enhancement by testing whether passive force enhancement occurs in single
      myofibrils. Myofibrils (n = 6) isolated from rabbit psoas muscle were fixed at a
      sarcomere length of 2.4 microm, and then stretched passively and actively to a
      sarcomere length of 3.4 microm. Passive force after deactivation of the
      myofibrils was increased after active compared to passive stretching. Therefore,
      passive force enhancement, previously observed in muscle and fiber preparations,
      also occurs in single myofibrils. Passive force enhancement in myofibrils ranged
      from 86 to 145% of the steady-state force observed after passive stretch. Because
      titin is the main source of passive force in myofibrils, we propose that titin
      might be responsible for passive force enhancement observed in myofibrils. We
      propose that this might occur through an increase in stiffness when calcium
      concentration increases upon activation.

PMID- 17551751
TI  - Characterization of amphioxus GDF8/11 gene, an archetype of vertebrate MSTN and
      GDF11.
AB  - MSTN, also known as growth and differentiation factor 8 (GDF8), and GDF11 are
      members of the transforming growth factor-beta (TGF-beta) subfamily. They have
      been thought to be derived from one ancestral gene. In the present study, we
      report the isolation and characterization of an invertebrate GDF8/11 homolog from
      the amphioxus (Branchiostoma belcheri tsingtauense). The amphioxus GDF8/11 gene
      consists of five exons flanked by four introns, which have two more exons and
      introns than that of other species. In intron III, a possible transposable
      element was identified. This suggested that this intron might be derived from
      transposon. The amphioxus GDF8/11 cDNA encodes a polypeptide of 419 amino acid
      residues. Phologenetic analysis shows that the GDF8/11 is at the base of
      vertebrate MSTNs and GDF11s. This result might prove that the GDF8/11 derived
      from one ancestral gene and the amphioxus GDF8/11 may be the common ancestral
      gene, and also the gene duplication event generating MSTN and GDF11 occurred
      before the divergence of vertebrates and after or at the divergence of amphioxus
      from vertebrates. Reverse transcriptase polymerase chain reaction results showed
      that the GDF8/11 gene was expressed in new fertilized cell, early gastrulation,
      and knife-shaped embryo, which was different from that in mammals. It suggested
      that the GDF8/11 gene might possess additional functions other than regulating
      muscle growth in amphioxus.

PMID- 17551752
TI  - Epithelial atypia in biopsies performed for microcalcifications. practical
      considerations about 2,833 serially sectioned surgical biopsies with a long
      follow-up.
AB  - This study analyzes the occurrence of epithelial atypia in 2,833 serially
      sectioned surgical breast biopsies (SB) performed for microcalcifications (median
      number of blocks per SB:26) and the occurrence of subsequent cancer after an
      initial diagnosis of epithelial atypia (median follow-up 160 months). Epithelial
      atypia (flat epithelial atypia, atypical ductal hyperplasia, and lobular
      neoplasia) were found in 971 SB, with and without a concomitant cancer in 301
      (31%) and 670 (69%) SB, respectively. Thus, isolated epithelial atypia were found
      in 670 out of the 2,833 SB (23%). Concomitant cancers corresponded to ductal
      carcinomas in situ and micro-invasive (77%), invasive ductal carcinomas not
      otherwise specified (15%), invasive lobular carcinomas (4%), and tubular
      carcinomas (4%). Fifteen out of the 443 patients with isolated epithelial atypia
      developed a subsequent ipsilateral (n = 14) and contralateral (n = 1) invasive
      cancer. The high slide rating might explain the high percentages of epithelial
      atypia and concomitant cancers and the low percentage of subsequent cancer after
      a diagnosis of epithelial atypia as a single lesion. Epithelial atypia could be
      more a risk marker of concomitant than subsequent cancer.

PMID- 17551754
TI  - Six-year stabilisation of a relapsed pelvic mass from rectal cancer after
      oxaliplatin-containing chemotherapy.
AB  - Chemotherapy alone without a multimodality approach has never been demonstrated
      to cure metastatic colorectal cancer patients. We report the case of a young
      woman referred in 1999 to our institution for a pelvic relapse of rectal cancer
      remained stable after oxaliplatin, 5-fluorouracil, and folinic acid therapy and
      never grown in size up to now, more than 6 years after the last relapse. Death of
      all the cancer cells, neuroendocrine cells selection, or cell dormancy are some
      of the discussed explanations to this unique observation. An intriguing question
      remains open: Should this patient be considered cured?

PMID- 17551755
TI  - Distribution of cells expressing Jun and Fos proteins and synthesizing DNA in the
      adrenal cortex of hypophysectomized rats: regulation by ACTH and FGF2.
AB  - Protein expression of the early response genes, jun and fos, has been suggested
      to play an important role in the in vitro and in vivo proliferation of adrenal
      cells. To elucidate the immunolocalization of proliferative cells and the
      patterns of adrenal gland expression of members of the activating protein-1 (AP
      1) family of oncogenes, we used hypophysectomized rats. The effects of
      adrenocorticotropic hormone (ACTH) and fibroblast growth factor 2 (FGF2) on Fos
      and Jun protein expression were investigated, and DNA synthesis was assessed by
      using bromodeoxyuridine (BrdU) incorporation. No change was detectable in the
      adrenal cortex at 2 days after hypophysectomy, although a reduction occurred in
      the number of BrdU-positive cells in the zona fasciculata. This hypophysectomy
      induced early phase of adrenal cortex atrophy in the zona fasciculata was
      correlated with JunB protein induction, suggesting the formation of an inhibitory
      AP-1 complex. Accumulation of c-Jun/JunD and c-Fos/FosB, but not of JunB, in the
      zona fasciculata and zona reticularis implied that, after ACTH stimulation, these
      proteins were the principal AP-1 components in these zones. In these same zones,
      ACTH increased BrdU-positive cell counts, indicating that the composition of the
      AP-1 complex in these zones was proliferation-related. However, FGF2 induced an
      antagonistic modulation of the response to ACTH, by reducing the numbers of Jun
      /Fos-positive cells and inhibiting DNA synthesis. Our results implicate the AP-1
      family of transcription factors (in particular, the dynamics within the Jun
      protein family) in the regulation of cell control during ACTH-induced
      proliferation of the adrenal cortex.

PMID- 17551756
TI  - Is focal segmental glomerulosclerosis increasing in patients with nephrotic
      syndrome?
AB  - Idiopathic nephrotic syndrome in children has conventionally been associated with
      minimal change disease. However, recent reports have conflictingly suggested that
      the frequency of focal segmental glomerulosclerosis (FSGS) in children might be
      on the increase, as has occurred in adults. The aim of the present work was to
      review the medical literature to ascertain whether an increase in the frequency
      of FSGS is occurring and, if so, to quantify such increase. We reviewed the
      studies comparing the frequency of FSGS in two consecutive periods over the past
      three decades (period 1 versus period 2). We pooled the data of the studies and
      then estimated FSGS frequency in two ways: (a) including in the denominator all
      patients with nephrotic syndrome and (b) including only patients who had
      undergone kidney biopsy. Both analyses were aimed to determine the odds ratio of
      FSGS occurrence in the second period. Six studies fulfilled the inclusion
      criteria, involving 1,149 patients with nephrotic syndrome. Four studies were
      used to calculate FSGS frequency, including in the denominator all nephrotic
      patients (n = 885), yielding an odds ratio of 2.22 (95% CI = 1.18-4.18). The
      analysis combining five studies with the number of biopsies in the denominator (n
      = 603) produced an odds ratio of 1.98 (95% CI = 1.12-3.50). These results suggest
      that a shift in the pathological pattern of nephrotic syndrome in children might
      be occurring, resulting in an increase in FSGS frequency. This hypothesis has
      major clinical significance due to the poorer prognosis associated with FSGS.

PMID- 17551753
TI  - Fungal infections in primary immunodeficiencies.
AB  - Patients with phagocytic, cellular, combined and other primary immunodeficiencies
      exhibit immune deficits that confer increased susceptibility to fungal
      infections. A number of yeasts and moulds, most commonly Candida and Aspergillus
      but also Cryptococcus, Histoplasma, Paecilomyces, Scedosporium, Trichosporon,
      Penicillium and other, rarely isolated, fungal organisms, have been variably
      implicated in causing disease in patients with chronic granulomatous disease,
      severe combined immunodeficiency, chronic mucocutaneous candidiasis, hyper-IgE
      syndrome, myeloperoxidase deficiency, leukocyte adhesion deficiency, defects in
      the interferon-gamma/interleukin-12 axis, DiGeorge syndrome, X-linked hyper-IgM
      syndrome, Wiskott-Aldrich syndrome and common variable immunodeficiency.
      Differences in the spectrum of fungal pathogens as well as in the incidence and
      clinical presentation of the infections may be observed among patients, depending
      upon different immune disorders. Fungal infections in these individuals may
      occasionally be the presenting clinical manifestation of a primary
      immunodeficiency and can cause significant morbidity and potentially fatal
      outcome if misdiagnosed or mistreated. A high degree of suspicion is needed and
      establishment of diagnosis should actively be pursued using appropriate imaging,
      mycological and histological studies. A number of antifungal agents introduced
      over the last fifteen years, such as the lipid formulations of amphotericin B,
      the second-generation triazoles, and the echinocandins, increase the options for
      medical management of these infections. Surgery may also be needed in some cases,
      while the role of adjunctive immunotherapy has not been systematically evaluated.
      The low incidence of primary immunodeficiencies in the general population
      complicates single-center prospective or retrospective clinical studies aiming to
      address diagnostic or therapeutic issues pertaining to fungal infections in these
      patients.

PMID- 17551757
TI  - [Self-assessed pain intensity and disability in subjects diagnosed with
      fibromyalgia claiming retirement pension].
AB  - INTRODUCTION: The clinical experience that subjects claiming retirement pension
      tend to aggravate their symptoms in psychometric tests has not yet, to our
      knowledge, been empirically tested. METHODS: Pain intensities and the summary
      score of the Pain Disability Index (PDI) of 83 consecutive subjects diagnosed
      with fibromyalgia syndrome (FMS) claiming retirement pension in medical
      assessment for the German Social Court were compared with 43 consecutive patients
      diagnosed with FMS of an outpatient pain department who did not claim retirement
      pension. Moreover, the relative predictive value of claiming retirement pension
      compared to other potential sociodemographic and clinical predictors of pain
      intensity and self-assessed disability was determined. RESULTS: Subjects claiming
      retirement pension within the context of medical testimony stated higher pain
      intensities and disabilities than patients who did not claim retirement pension
      (P<0.01 in all cases). Claiming disability pension was an independent predictor
      of minimum pain intensity (r(2)=0.10, P=0.02), of maximum pain intensity
      (r(2)=0.16, P=0.002) and of the summary score of the PDI (r(2)=0.08, P=0.008).
      CONCLUSIONS: The association between claiming retirement pension and high self
      assessed pain and disability should be kept in mind in the context of pain
      therapy as well of medical expertise.

PMID- 17551758
TI  - Do bowerbirds exhibit cultures?
AB  - Definitions of what features constitute cultural behaviour, and hence define
      cultures are numerous. Many seem designed to describe those aspects of human
      behaviour which set us apart from other animals. A broad definition prescribing
      that the behaviour is: learned; learned socially; normative and collective is
      considered to apply to several species of great ape. In this paper, I review
      observations and experiments covering a suite of different behavioural
      characteristics displayed in members of the bowerbird family (Ptilonorhynchidae)
      and ask whether they fulfil these criteria. These include vocalisations, bower
      design, decoration use, bower orientation and display movements. Such a range of
      behaviours refutes the suggestion that these species are "one-trick ponies"--a
      criticism that is often levelled at claims for culture in non-primate species. I
      suggest that, despite a paucity of data in comparison with primate studies, it
      could be argued that bowerbirds may be considered to fulfil the same criteria on
      which we base our use of the term culture when applied to our close relatives,
      the great apes. If bowerbirds do have cultures, then their unusual natural
      history makes them a highly tractable system in which questions of social
      learning and culture can be tackled.

PMID- 17551759
TI  - Antimicrobial use in Europe and antimicrobial resistance in Streptococcus
      pneumoniae.
AB  - The study presented here determined the relationship between antimicrobial
      resistance in Streptococcus pneumoniae and the use of antimicrobial agents in 15
      different European countries. Pneumococcal isolates (n = 1974) recovered from
      patients with community-acquired respiratory tract infections during the winter
      of 2004-2005 in 15 European countries were characterized. The overall percentages
      of isolates demonstrating intermediate or complete resistance to penicillin,
      erythromycin, tetracycline, trimethoprim-sulfamethoxazole (TMP-SMX) and
      ciprofloxacin were 24, 24.6, 19.8, 26.7 and 2%, respectively, as determined using
      the broth microdilution MIC method recommended by the Clinical and Laboratory
      Standards Institute. The overall and mean antimicrobial consumption levels (ACL)-
      i.e., the defined daily doses per 1,000 inhabitants per day--were obtained from
      the European Surveillance of Antimicrobial Consumption project for each of the 15
      countries for the years 1998-2004. Using linear regression analysis, the mean
      annual ACL for beta-lactams, macrolides, tetracyclines, TMP-SMX and
      fluoroquinolones in each country was compared to the country-specific resistance
      rates determined in 2004-2005. The rate of overall antimicrobial use in all 15
      European countries was significantly associated with antimicrobial resistance in
      S. pneumoniae. There was variation among the different antimicrobial classes as
      drivers of resistance, with beta-lactams having the strongest association.

PMID- 17551760
TI  - Isolation and characterization of a new bacteriocin, termed enterocin M, produced
      by environmental isolate Enterococcus faecium AL41.
AB  - The new bacteriocin, termed enterocin M, produced by Enterococcus faecium AL 41
      showed a wide spectrum of inhibitory activity against the indicator organisms
      from different sources. It was purified by (NH4)2SO4 precipitation, cation
      exchange chromatography and reverse phase chromatography (FPLC). The purified
      peptide was sequenced by N-terminal amino acid Edman degradation and a mass
      spectrometry analysis was performed. By combining the data obtained from amino
      acid sequence (39 N-terminal amino acid residues was determined) and the
      molecular weight (determined to be 4628 Da) it was concluded that the purified
      enterocin M is a new bacteriocin, which is very similar to enterocin P. However,
      its molecular weight is different from enterocin P (4701.25). Of the first 39 N
      terminal residues of enterocin M, valine was found in position 20 and a lysine in
      position 35, while enterocin P has tryptophane residues in these positions.

PMID- 17551761
TI  - A novel simulation algorithm for soft tissue compression.
AB  - This paper presents a novel general approach to simulation of soft tissue
      compression. A theoretical framework of the compression algorithm has been
      developed and implemented, based on the concept of a simple spring. The volume
      subjected to compression is divided into a number of "model elements", each one
      consisting of 27 nodes. The nodes are connected with springs. The mechanical
      properties of the tissues are assumed to be linear and isotropic. The compressed
      volume remains constant due to the introduced concept of spring variable
      equilibrium lengths. Initial settings for compression simulation are introduced
      in order that the algorithm converges faster. The developed compression algorithm
      was used to model breast compression during a standard mammography examination.
      Specifically, the method was applied to a high-resolution three-dimensional
      software breast phantom, composed to have a medium glandularity and calcification
      abnormalities. The compression was set to 50%. Results showed that the
      abnormalities maintain their shape and dimensions during the compression, while
      the surrounding breast tissues undergo considerable deformation and displacement.
      A "decompression" algorithm was also applied to test the reversibility of the
      model.

PMID- 17551762
TI  - Effects of cigarette smoke on cell viability, linoleic acid metabolism and
      cholesterol synthesis, in THP-1 cells.
AB  - Cigarette smoke (CS) contains thousands of substances, mainly free radicals that
      have as a target the polyunsaturated fatty acids (PUFA). Long chain PUFA are
      produced through elongation and desaturation reactions from their precursors; the
      desaturation reactions are catalyzed by different enzymes: the conversion of
      18:2n-6 (linoleic acid, LA) to 18:3n-6 by Delta6 desaturase, while that of 20:3n
      6 to 20:4n-6 by Delta5 desaturase. The aim of this work is to evaluate the effect
      of serum exposed to cigarette smoke (SE-FBS) on (1) cell viability and
      proliferation, (2) [1-(14)C] LA conversion and desaturase activities in THP-1
      cells, a monocytic cell line. In THP-1, CS inhibits cell proliferation dose
      dependently, by producing a modification in the cell cycle with a reduced number
      of cells in synthesis and mitosis phases at higher concentrations. CS also
      decreases [1-(14)C] LA conversion to its derivatives in a concentration-dependent
      manner, inhibiting the activities of Delta6 and mainly Delta5 desaturase. In
      addition, CS does not modify the incorporation of LA into various lipid classes
      but it reduces cholesterol synthesis from radiolabelled acetate, and increases
      free fatty acid, TG and CE levels. In conclusion, CS affects lipid metabolism,
      inhibiting LA conversion and desaturase activities. CS also shifts the "de novo"
      lipid synthesis from free cholesterol to TG and CE, where LA is preferentially
      esterified.

PMID- 17551763
TI  - Respective hydrolysis and esterification of esterified and free plant stanols
      occur rapidly in human intestine after their duodenal infusion in triacyl- or
      diacylglycerol.
AB  - Esterification of dietary phytosterols and glycerols may affect intestinal
      absorption of cholesterol and non-cholesterol sterols. We infused plant stanol
      esters in triacylglycerol (TAG) (F1) and diacylglycerol (DG) (F2) oils, and free
      plant stanols in F1 and F2 (F3) to the duodenum of healthy human subjects and
      sampled the contents from the proximal jejunum (PJ). Free and ester sterols were
      analysed from the infusates, and intestinal contents before and after
      ultracentrifuge separation of oil, micelle and sediment phases. During the 60-cm
      intestinal passage, over 40% of plant stanol esters were hydrolysed (P < 0.05)
      but around 30% of the infused free plant stanols (P < 0.05) and up to 40% of
      cholesterol (P < 0.05) were esterified in PJ after infusions. TAG in F1 favoured
      accumulation of plant stanol esters in the oil phase of the PJ aspirates as
      compared with respective values of F2 and F3 (P < 0.05 for both). About one third
      of free plant stanols of F3 had been esterified (P < 0.05) and 17% precipitated
      mainly in free form in the PJ aspirates (P < 0.05 compared with F1 and F2). In
      conclusion, DG- and TAG-oils had no profound superiority over each other as
      intestinal carriers regarding hydrolysis/esterification of administered plant
      stanol esters and cholesterol and their partition in oil, micellar and sediment
      phases in the PJ. The unesterified plant stanols experienced partial
      esterification and sedimentation during their intestinal passage, which might
      influence their biochemical properties in that segment of the gut where
      cholesterol is absorbed.

PMID- 17551764
TI  - Incorporation of arachidonic and stearic acids bound to L-FABP into nuclear and
      endonuclear lipids from rat liver cells.
AB  - The incorporation of exogenous fatty acids bound to L-FABP into nuclei was
      studied. Rat liver cell nuclei and nuclear matrices (membrane depleted nuclei)
      were incubated in vitro with [1-(14)C]18:0 and 20:4n-6 either free or bound to L
      FABP, ATP and CoA. FA esterification in whole nuclei and endonuclear lipids was
      ATP-CoA-dependent, and with specificity regarding fatty acid type and lipid
      class. 18:0 and 20:4n-6, free or L-FABP bound, showed the same incorporation and
      esterification pattern in lipids of whole nuclei. Only 20:4n-6 L-FABP bound was
      less incorporated into TAG with respect to free 20:4n-6. In the nuclear matrix,
      18:0 free or L-FABP bound was esterified with a higher specific activity (SA)
      into: PtdEtn > PtdIns, PtdSer > PtdCho. 20:4n-6 free or L-FABP bound was
      esterified into: PtdIns > PtdEtn > PtdCho. 20:4n-6:L-FABP was esterified in
      endonuclear total-PL and PtdIns with a greater SA with respect to free 20:4n-6
      and with a minor one as FFA. To summarize, trafficking of FA to nuclei includes
      esterification of 18:0 and 20:4n-6 either free or L-FABP-bound, into nuclear and
      endonuclear lipids by an ATP-CoA-dependent pathway. Endonuclear fatty acid
      esterification was more active than that in whole nuclei, and independent of the
      nuclear membrane. Esterification patterns of fatty acids L-FABP-bound or free
      into whole nuclear lipids were the same whereas in the nuclear matrix, L-FABP
      could play an important role in the mobilization of 20:4n-6 into specific sites
      of utilization such as the PtdIns pools.

PMID- 17551766
TI  - Effects of treatment of ovariectomized adult rhesus monkeys with parathyroid
      hormone 1-84 for 16 months on trabecular and cortical bone structure and
      biomechanical properties of the proximal femur.
AB  - Treatment of monkeys and humans with parathyroid hormone (PTH) 1-84 stimulates
      skeletal remodeling, which increases trabecular (Tb) bone mineral density (BMD)
      but decreases cortical (Ct) BMD at locations where these bone types predominate.
      We report the effects of daily PTH treatment (5, 10, or 25 microg/kg) of
      ovariectomized (OVX) rhesus monkeys for 16 months on bone structure and
      biomechanical properties at the proximal femur, a mixed trabecular and cortical
      bone site. PTH reversed the OVX-induced decrease in BMD measured by dual-energy X
      ray absorptiometry at the proximal femur, femoral neck, and distal femur.
      Peripheral quantitative computed tomography confirmed a significant decrease in
      Ct.BMD and an increase in Tb.BMD at the total proximal femur and at the proximal
      and distal femoral metaphyses. The decrease in Ct.BMD resulted primarily from
      increased area because cortical bone mineral content was unaffected by PTH.
      Histomorphometry revealed that PTH significantly increased the trabecular bone
      formation rate (BFR) as well as trabecular bone volume and number. PTH did not
      affect periosteal or haversian BFR at the femoral neck, but cortical porosity was
      increased slightly. PTH had no effects on stiffness or peak load measured using a
      shear test, whereas work-to-failure, the energy required to fracture, was
      increased significantly. Thus, PTH treatment induced changes in trabecular and
      cortical bone at the proximal femur that were similar to those occurring at sites
      where these bone types predominate. Together, the changes had no effect on
      stiffness or peak load but increased the energy required to break the proximal
      femur, thereby making it more resistant to fracture.

PMID- 17551767
TI  - Carbonate assignment and calibration in the Raman spectrum of apatite.
AB  - A series of apatites with varying carbonate levels was prepared in order to
      assign the carbonate bands and calibrate for Raman analysis of natural materials.
      Overlap of carbonate bands with phosphate peaks was resolved by curve fitting. A
      peak at 1,071 cm(-1) was assigned to a combination of the carbonate nu(1) mode at
      1,070 cm(-1) with a phosphate nu(3) mode at 1,076 cm(-1). In addition, the
      carbonate nu(4) mode was identified in apatite samples with >4% carbonate. The
      carbonate nu(4) bands at 715 and 689 cm(-1) identify the samples as B-type
      carbonated apatite. The carbonate content of apatite was calibrated to a
      carbonate Raman band, and the method was used to determine the carbonate content
      of a sample of bovine cortical bone, 7.7 +/- 0.4%.

PMID- 17551768
TI  - The -1997 G/T and Sp1 polymorphisms in the collagen type I alpha1 (COLIA1) gene
      in relation to changes in femoral neck bone mineral density and the risk of
      fracture in the elderly: the Rotterdam study.
AB  - The COLIA1 Sp1 polymorphism has been associated with bone mineral density (BMD)
      and fracture. A promoter polymorphism, -1997 G/T, also has been associated with
      BMD. In this study, we examined whether these polymorphisms alone and in the form
      of haplotypes influence bone parameters and fracture risk in a large population
      based cohort of elderly Caucasians. We determined the COLIA1 -1997 G/T (promoter)
      and Sp1 G/T (intron) polymorphisms in 6,280 individuals and inferred haplotypes.
      Femoral neck BMD and BMD change were compared across COLIA1 genotypes at baseline
      and follow-up (mean 6.5 years). We also investigated the relationship between the
      COLIA1 polymorphisms and incident nonvertebral fractures, which were recorded
      during a mean follow-up period of 7.4 years. Vertebral fractures were assessed by
      radiographs on 3,456 genotyped individuals. Femoral neck BMD measured at baseline
      was 3.8% lower in women carrying two copies of the T-Sp1 allele (P for trend =
      0.03). No genotype dependent differences in BMD loss were observed. In women
      homozygous for the T allele of the Sp1 polymorphism, the risk of fragility
      fracture increased 2.3 times (95% confidence interval 1.4-3.9, P = 0.001). No
      such association was observed with the promoter polymorphism. In men, no
      association with either the Sp1 or the -1997 G/T promoter polymorphism was seen
      with BMD or fracture. High linkage disequilibrium (LD; D' = 0.99, r (2 )= 0.03)
      exists between the two studied polymorphisms. We observed three haplotypes in our
      population: haplotype 1 (G(promoter)-G(intron)) frequency (f) = 69%, haplotype 2
      (G(promoter)-T(intron)) f = 17.6%, and haplotype 3 (T(promoter)-G(intron)) f =
      13.4%. Haplotype 2 was associated with a 2.1-fold increased risk of fragility
      fracture in women (95% confidence interval 1.2-3.7, P = 0.001). We confirm that
      the COLIA1 Sp1 polymorphism influences BMD and the risk of fracture in
      postmenopausal Caucasian women. In contrast, we found no independent effect of
      the -1997 G/T promoter polymorphism on BMD or fracture.

PMID- 17551769
TI  - Altered collagen in tartrate-resistant acid phosphatase (TRAP)-deficient mice: a
      role for TRAP in bone collagen metabolism.
AB  - Tartrate-resistant acid phosphatase (TRAP) is an iron-containing protein that is
      highly expressed by osteoclasts, macrophages, and dendritic cells. The enzyme is
      secreted by osteoclasts during bone resorption, and serum TRAP activity
      correlates with resorptive activity in disorders of bone metabolism. TRAP is
      essential for normal skeletal development. In knockout mice lacking TRAP, bone
      shape and modeling is altered with increased mineral density. Here, we report the
      effect of TRAP on the biochemical and biomechanical properties of collagen, the
      major protein constituting the bone matrix, using these mice. Femurs from TRAP-/-
      and wild-type mice were used in these studies. The biomechanical properties were
      investigated using a three-point bending technique. Collagen synthesis was
      determined by measuring cross-link content using high-performance liquid
      chromatography and amino acid analysis. Collagen degradation was determined by
      measuring matrix metalloproteinase-2 (MMP-2) activity. The rates of collagen
      synthesis and degradation were significantly greater in bones from TRAP-/- mice
      compared with wild type. At 8 weeks, there was an increase in the intermediate
      cross-links but no significant difference in animals aged 6 months. There was a
      significant increase in mature cross-links at both ages. A significant increase
      in MMP-2 production both pro and active was observed. A significant increase in
      ultimate stress and Young's modulus of elasticity was needed to fracture the
      bones from mice deficient in TRAP. We conclude that both synthesis as well as
      degradation of collagen are increased when TRAP is absent in mice at 8 weeks and
      6 months of age, showing that TRAP has an important role in the metabolism of
      collagen.

PMID- 17551770
TI  - Damaging fatigue loading stimulates increases in periosteal vascularity at sites
      of bone formation in the rat ulna.
AB  - Bone formation in a variety of contexts depends on angiogenesis; however, there
      are few reports of the vascular response to osteogenic skeletal loading. We used
      the rat forelimb compression model to characterize vascular changes after fatigue
      loading. The right forelimbs of 72 adult rats were loaded cyclically in vivo to
      one of four displacement levels, to produce four discrete levels of ulnar damage.
      Rats were killed 3-14 days after loading, and their vasculature was perfused with
      silicone rubber. Transverse histological sections were cut along the ulnar
      diaphysis. We quantified vessel number, average vessel area, total vessel area,
      and bone area. On day 3, we observed a dramatic periosteal expansion near the
      ulnar midshaft, with significant increases in periosteal vascularity; total
      vessel area was increased 250-450% (P < 0.001). Vascularity remained elevated on
      days 7 and 14. Vessel number and average vessel area were not correlated (P =
      0.09) and contributed independently to total vascular increases. Bone area was
      not increased on day 3 but on days 7 and 14 was increased significantly in all
      displacement groups (P < 0.01) due to periosteal woven bone formation. Vascular
      and bone changes depended on longitudinal location (P < 0.001), with peak
      increases 2 mm distal to the midshaft. Vascular and bone changes also depended on
      displacement level (P < 0.005), with greater increases at higher levels of
      fatigue displacement. We conclude that skeletal fatigue loading induces a rapid
      increase in periosteal vascularity, followed by an increase in bone area. The
      angiogenic-osteogenic response is spatially coordinated and scaled to the level
      of the mechanical stimulus.

PMID- 17551771
TI  - Quantitative trait loci that determine mouse tibial nanoindentation properties in
      an F2 population derived from C57BL/6J x C3H/HeJ.
AB  - Use of nanoindentation technology to identify quantitative trait loci (QTL) that
      regulate bone properties represents a novel approach to improving our
      understanding of molecular mechanisms that control bone matrix properties. Tibiae
      for QTL mapping were from an F2 population derived from C57BL/6J and C3H/HeJ. A
      nanoindenter (Triboindenter; Hysitron, Minneapolis, MN) was used to conduct
      indentation tests on transverse sections. Genotyping was performed in The Jackson
      Laboratory. QTL mapping was conducted using software. We found that (1) tibiae
      from mice at 16 weeks of age were mature and suitable for measurement by a
      nanoindentor; (2) both stiffness modulus and hardness modulus in the F2
      population appeared to have normal distributions, which suggested that multiple
      genetic factors control the bone properties; and (3) QTL for hardness were
      identified from five chromosomes (Chr 8, 12, 13, 17, and 19) and for stiffness,
      from four chromosomes (Chr 3, 8, 12, and 13). Among all detected QTL, one at the
      same location on Chr 12 was detected for both hardness and stiffness data. It
      explained the highest percentage of phenotypic variation in bone properties.
      Using nanoindentation technology to identify QTL that regulate bone properties
      yielded as many as six different chromosomal regions. Although the actual genes
      remain to be identified, nanoindentation will contribute to our understanding of
      molecular mechanisms and normal development processes that control the matrix
      properties of bone.

PMID- 17551772
TI  - Long-term support with milrinone prior to cardiac transplantation in a neonate
      with left ventricular noncompaction cardiomyopathy.
AB  - A 2-week-old female infant presented with acute decompensated left ventricular
      failure. Echocardiography diagnosed left ventricular noncompaction cardiomyopathy
      with dilated phenotype and a left ventricular shortening fraction <10%. The
      infant was mechanically ventilated for 2 weeks and then successfully extubated.
      She was maintained on intravenous milrinone for 6 months until she underwent
      successful orthotopic heart transplantation. Young children can be supported with
      inotropes for prolonged periods while awaiting heart transplantation.

PMID- 17551773
TI  - Safe total corporal contouring with large-volume liposuction for the obese
      patient.

PMID- 17551774
TI  - Use of 6-year-old preserved autogenous septal cartilage in secondary rhinoplasty.

PMID- 17551775
TI  - Influence of rifampin on capsule formation around silicone implants in a rat
      model.
AB  - This study investigated the effect of rifampin on the thickness of capsules
      around silicone implants by bactericidal activity against Stapylococcus
      epidermidis. Silicone blocks (1 x 1 cm) were placed into pockets created for each
      of the 40 rats included in the study. In group 1, the operation was performed
      under aseptic conditions. In group 2, standard S. epidermidis was inoculated into
      the pocket, whereas rifampin and S. epidermidis were applied in group 3. In group
      4, only rifampin was applied topically on implants. After 12 weeks, the peri
      implant capsules were removed and examined under a photomicroscope and a scanning
      electron microscope. The mean thickness of the capsules was 63.307 microm in
      group 1, 111.538 microm in group 2, 43.076 microm in group 3, and 30.384 mum in
      group 4. The differences between groups 2 and 3 and groups 2 and 4 were found to
      be statistically significant (p < 0.001). Rifampin appears to be an agent for
      preventing peri-implant capsule formation.

PMID- 17551776
TI  - The central role of the nose in the face and the psyche: review of the nose and
      the psyche.
AB  - BACKGROUND: According to statistics released by the American Society of Plastic
      Surgeons in 2006, rhinoplasty is one of the most sought after aesthetic surgeries
      by ethnic patients and teenagers. It also is the most requested aesthetic
      operation by patients with body dysmorphic disorder. The psychosocial aspect of
      rhinoplasty is undeniable. Tagliacozzi in 1567 and Joseph more than a century ago
      were already aware of this aspect. METHODS: Using the terms "rhinoplasty,"
      "patients selection," "psychological aspect," and psychological outcome," 30
      studies were selected through searches of the MEDLINE, PUBMED, and EMBASE
      databases,. This review aimed to analyze how the most acknowledged experts of
      psychology, facial plastic surgery, and plastic surgery who have worked on the
      psychological outcome for rhinoplasty during the past century considered the nose
      psyche relationship and the influence of rhinoplasty at the psychological level.
      RESULTS: The link between rhinoplasty, psychology, and social environment has
      been discussed by many important authors during the past century. All of them,
      independently of their field of study, have stressed that it is critical for
      surgeons to be aware of their responsibility regarding both the physical and
      emotional levels. There is evidence that an official preoperative interview is
      lacking. CONCLUSIONS: To recognize the importance of rhinoplasty's psychological
      implications, it is critical to make a good selection of patients seeking this
      operation and to have a good outcome. To this end, the preoperative interview is
      fundamental. Surgeons should be competent at both the psychological and surgical
      levels.

PMID- 17551777
TI  - Polyurethane-coated silicone gel breast implants used for 18 years.
AB  - This study aimed to present an update on the use of polyurethane-coated silicone
      gel breast implants. After 18 years of experience using these implants and 1,257
      surgically treated patients, the authors can draw some new conclusions. Their
      postoperative follow-up evaluation of 300 patients for 5 years, 250 patients for
      10 years, and 180 patients for 15 years has shown the lowest incidence of fibrous
      capsular contraction (1%) with these implants.

PMID- 17551778
TI  - Nosocomial infections after peripheral arterial bypass surgery.
AB  - BACKGROUND: Hospital-acquired infections account for a substantial increase in
      morbidity and mortality. This prospective, single-center observational study was
      conducted to assess the incidence and analyze the risk factors of nosocomial
      infection after peripheral arterial bypass surgery. METHODS: The incidence of
      nosocomial infections was registered in all patients undergoing peripheral
      arterial bypass surgery from January 1996 until December 2004, and risk factors
      for the development of a nosocomial infection were analyzed. RESULTS: A total of
      67 infections were diagnosed in association with 607 procedures, yielding an
      infection ratio of 10.0%. Surgical site infection was the most common (55.2%),
      followed by urinary tract infection (16.4%), pneumonia (14.9%) and bacteremia
      (10.4%). Staphylococcus aureus was the most commonly found isolate in surgical
      site infections (48.6%) and in bacteremia (42.9%). Age, the use of
      corticosteroids (p = 0.02), and critical ischemia with tissue loss (p = 0.009)
      could be identified as risk factors for the development of a nosocomial
      infection. Blood transfusion was a postoperative risk factor for nosocomial
      infection (p < .0001). Nosocomial infection was associated with a prolonged
      hospital stay (p < .0001). CONCLUSIONS: This study provides a detailed
      description of the incidence and risk factors regarding nosocomial infection.
      More detailed studies are necessary to develop strategies to diminish the
      occurrence of nosocomial infection.

PMID- 17551779
TI  - Postoperative liver dysfunction and future remnant liver: where is the limit?
      Results of a prospective study.
AB  - BACKGROUND: The future remnant liver (FRL) limit for safe major hepatectomy with
      low risk of postoperative liver failure has not yet been well defined. METHODS:
      Between April 2000 and September 2004, every patient scheduled for major
      hepatectomy in our institution underwent CT-volumetry of FRL. Patients with FRL
      <25% underwent portal vein embolization (PVE). Exclusion criteria were PVE,
      associated vascular resection and liver cirrhosis. The FRL was correlated with
      short-term results in patients with normal liver (group A) and those with
      impaired liver function secondary to neoadjuvant chemotherapy or cholestasis
      (bilirubin >2 mg/100 ml) (group B). Liver dysfunction was defined as both PT <50%
      and serum bilirubin level >5 mg/100 ml for three or more consecutive days.
      RESULTS: A total of 119 patients were analyzed, 72 in group A and 47 in group B.
      The FRL value was the only significant risk factor for postoperative liver
      dysfunction in the univariate and multivariate analysis (p = 0.009). The FRL did
      not correlate with postoperative mortality and morbidity. Bilirubin and
      prothrombin time (PT) on days 3 and 7 were significantly correlated to FRL in
      both groups. In group A, patients with postoperative liver dysfunction had a
      FRL<30% (3 versus 0; p = 0.005). According to receiving operator characteristic
      (ROC) curve analysis, a FRL value of 26.5% predicted postoperative liver
      dysfunction with 66.7% sensitivity, 97.1% specificity, 50% positive predictive
      value (PPV), and 98.5% negative predictive value (NPV). In group B, patients with
      postoperative liver dysfunction had a FRL <35% (4 versus 0; p = 0.027). According
      to ROC curve analysis, a FRL value of 31.05% predicted postoperative liver
      dysfunction with 75% sensitivity, 79.1% specificity, 25% PPV, and 97.1% NPV.
      CONCLUSIONS: Hepatectomy can be considered safe when FRL is >26.5% in patients
      with healthy liver and >31% in patients with impaired liver function.

PMID- 17551780
TI  - Sternocleidomastoid muscle myocutaneous flap for corrosive pharyngoesophageal
      strictures.
AB  - BACKGROUND: Strictures at the pharyngoesophageal junction represent a subgroup of
      corrosive esophageal strictures requiring a specialized management approach. Non
      dilatable cricopharyngeal strictures need surgical intervention. We report the
      use of the sternocleidomastoid muscle myocutaneous inlay flap (SCMMIF) for
      reconstruction of the cervical esophagus in patients with corrosive strictures.
      METHODS: A SCMMIF was used in four patients with cricopharyngeal strictures. The
      surgical technique is described. All patients had complete dilatation of the
      stenosed cricopharyngeal segment as seen on postoperative endoscopy and contrast
      studies. One patient was managed successfully for a short midesophageal stricture
      by serial endoscopic dilatations. Another patient underwent an esophagocoloplasty
      subsequently for bypass of the long distal esophageal stricture The last two
      patients await esophagocoloplasty. CONCLUSIONS: This is the first report on the
      use of sternocleidomastoid muscle myocutaneous inlay flap for corrosive
      cricopharyngeal strictures. The flap is simple to construct, is effective and can
      be performed in a short time, and yields good cosmetic results.

PMID- 17551781
TI  - Perioperative vasopressors are associated with an increased risk of
      gastrointestinal anastomotic leakage.
AB  - BACKGROUND: The purpose of this study was to investigate the effect of
      vasopressors on gastrointestinal (GI) anastomotic leaks. Vasopressors are
      commonly used in surgical patients admitted to the intensive care unit (ICU) and
      their effects on GI anastomotic integrity are unknown. PATIENTS AND METHODS:
      Surgical patients admitted to the ICU in our tertiary university hospital
      following the creation of a GI anastomosis were studied by a retrospective chart
      analysis for anastomotic leaks and complications RESULTS: A total of 223 patients
      with 259 GI anastomoses, mostly for cancer, were admitted to the ICU immediately
      after surgery. Twenty-two patients developed anastomotic leaks (9.9%). The two
      groups (leak versus no-leak) had similar demographics, surgery type and
      indication, type of anastomosis, co-morbidities, cancer, steroid use, blood
      transfusion, drains, and epidural catheters. Vasopressor use was associated with
      increased anastomotic leakage (p = 0.02, OR 3.25). Multiple vasopressors and
      prolonged exposure caused even higher leaking rates. This effect was independent
      of the medical status and operative morbidity (APACHE II, POSSUM). Blood pressure
      preceding vasopressor use was similar in both groups. Vasopressors might have
      been occasionally used to treat hypovolemia. Patients with leaks had higher
      reoperation rates (41% versus 1%, p < 0.0001) and mortality (21% versus 4%, p =
      0.002). CONCLUSIONS: Vasopressors appear to increase anastomotic leaks threefold,
      independent of clinical/surgical status or hypotension. Evidence-based guidelines
      are warranted for the optimal use of vasopressors in postoperative patients
      admitted to the ICU.

PMID- 17551782
TI  - Pyrrolidine dithiocarbamate reduces lung injury caused by mesenteric
      ischemia/reperfusion in a rat model.
AB  - BACKGROUND: Pyrrolidine dithiocarbamate (PDTC) is a low-molecular thiol
      antioxidant and potent inhibitor of nuclear factor-kappaB (NF-kappaB) activation.
      It has been shown to attenuate local harmful effects of ischemia/reperfusion
      (I/R) injury in many organs. In this study, we aimed to study the effect of PDTC
      on lung reperfusion injury induced by superior mesenteric occlusion. METHODS:
      Male Wistar-albino rats randomized into three groups: (1) sham-operated control
      group (n = 12), laparotomy without I/R injury; (2) intestinal
      ischemia/reperfusion (I/R) group (n = 12), 60 min of ischemia by superior
      mesenteric occlusion followed by 2 h of reperfusion; and (3) I/R+PDTC-treated
      group (n = 12), 100 mg/kg injection of PDTC intravenously, 30 min after the
      commencement of reperfusion. Evans blue dye was injected to half of rats in all
      groups before the induction of I/R. We assessed the degree of pulmonary tissue
      injury biochemically by measuring malondialdehyde (MDA), glutathione (GSH), and
      nitric oxide (NO) levels, and histopathologically by establishing pulmonary
      neutrophil sequestration and acute lung injury scoring. Pulmonary edema was
      evaluated by Evans blue dye extravasation, as well as lung tissue wet/dry weight
      ratios. RESULTS: Pyrrolidine dithiocarbamate treatment significantly reduced the
      MDA and NO levels, and increased the GSH levels in the lung parenchyma,
      biochemically (p < 0.05), and atteneuated the pulmonary parenchymal damage,
      histopathologically (p < 0.05). However, pulmonary neutrophil sequestration was
      not affected by postischemic treatment with PDTC (p > 0.05). Pyrrolidine
      dithiocarbamate administration also significantly alleviated the formation of
      pulmonary edema, as evidenced by the decreased Evans blue dye extravasation and
      organ wet/dry weight ratios (p < 0.05). CONCLUSIONS: This study showed that
      postischemic treatment with PDTC significantly attenuated the lung reperfusion
      injury. Further clinical studies are needed for better understanding of the
      specific mechanisms of PDTC protection against I/R-related organ injury and to
      clarify whether PDTC may be a useful therapeutic agent during particular
      operations where remote organ I/R injury occurs.

PMID- 17551783
TI  - Role of hyperbaric oxygen therapy in the treatment of postoperative organ/space
      sternal surgical site infections.
AB  - BACKGROUND: A prospective trial was designed to evaluate the effect of hyperbaric
      oxygen (HBO) therapy on organ/space sternal surgical site infections (SSIs)
      following cardiac surgery that requires sternotomy. METHODS: A total of 32
      patients who developed postoperative organ/space sternal SSI were enrolled in
      this study from 1999 through 2005. All patients were offered HBO therapy. Group 1
      included the patients who accepted and were able to undergo HBO therapy (n = 14);
      group 2 included patients who refused HBO therapy or had contraindications to it
      (n = 18). RESULTS: The two groups were well matched at baseline with comparable
      preoperative clinical characteristics and operative factors. Staphylococcus was
      the most common pathogen for both groups. The duration of infection was similar
      in groups 1 and 2 (31.8 7.6 vs. 29.3 5.7 days, respectively, p = 0.357). The
      infection relapse rate was significantly lower in group 1 (0% vs. 33.3%, p =
      0.024). Moreover, the duration of intravenous antibiotic use (47.8 +/- 7.4 vs.
      67.6 +/- 25.1 days, p = 0.036) and total hospital stay (52.6 +/- 9.1 vs. 73.6 +/-
      24.5 days, p = 0.026) were both significantly shorter in group 1. CONCLUSION:
      Hyperbaric oxygen is a valuable addition to the armamentarium available to
      physicians for treating postoperative organ/space sternal SSI.

PMID- 17551784
TI  - Reinforcement of endocrine surgery training: impact of telemedicine technology in
      a developing country context.
AB  - AIMS AND OBJECTIVES: Technology-based outreach programs for knowledge sharing and
      skill development using telemedicine is a novel approach to developing
      subspecialties in regions where there is a lack of specialists and dedicated
      departments. Endocrine surgery is one such emerging subspecialty. There are few
      dedicated surgeons and centers even in the developed world. India has only one
      such center. The aim of this study was to assess the feasibility and impact of
      telemedicine on the reinforcement of endocrine surgery training at distant places
      to develop this subspecialty in a developing country such as India. MATERIAL AND
      METHODS: Two faculty members from the General Surgery Department at SCB Medical
      College in Cuttack, Orissa, India registered at Sanjay Gandhi Postgraduate
      Institute of Medical Sciences in Lucknow for a short 3-month training course in
      endocrine surgery in 1998 and thereafter consulted through telephone calls and e
      mail when required. Telemedicine-based mentoring was introduced in 2001 as a
      reinforcement method for continuing training and skills development. Various
      training modules were used, including tele-consultation, case presentation,
      treatment planning, tele-radiology, tele-pathology, and tele-continuing medical
      education (CME) programs and workshops. The outcome was assessed in terms of the
      increase in the number of patients with endocrine disorders seen and operated on
      by trainees and the complication rates. RESULTS: A total of 70 telemedicine
      sessions were held between 2001 and 2005. They included tele-education and
      surgical treatment planning (n = 44), tele-consultation including tele-pathology
      and tele-radiology (n = 26), and tele-surgical conferences/CME (n = 6). The
      number of endocrine surgical cases performed by trainees after training (phase
      II) increased significantly compared to those before training (phase I), with a
      further increase after starting telemedicine-enabled mentoring (phase III). Most
      of the patients operated on by the trainees had thyroid problems, although these
      surgeons started operating on a few patients with parathyroid and adrenal
      disorders as well. The morbidity figures for the thyroidectomy operations
      (including total thyroidectomy) were comparable to those at the training
      institution. CONCLUSION: The concept of training a group of motivated general
      surgeons to practice safe endocrine surgery at a remote center via telemedicine
      aided reinforcement of their training is thus feasible. This is particularly true
      in the case of thyroidectomy operations, which constitute the major workload of
      endocrine surgery in our country. The same program might be applicable to the
      development of other medical subspecialties in a developing country as well.

PMID- 17551786
TI  - Revisiting Wolbachia supergroup typing based on WSP: spurious lineages and
      discordance with MLST.
AB  - The obligate intracellular bacteria Wolbachia are taxonomically subdivided into
      eight supergroups (named A-H). Supergroup typing of strains has been mostly based
      on phylogenetic inference of the Wolbachia surface protein (wsp), a gene that
      recently has been shown to experience high rates of recombination. This brings
      into question its suitability not only for microtaxonomy, but also for supergroup
      classification of the genus. A Multilocus Sequence Typing (MLST) scheme for
      Wolbachia has recently been developed that types strains based on five conserved
      genes, thus providing a rigorous supergroup annotation of strains. Here we report
      striking discrepancies in supergroup designation between MLST and wsp inferences,
      and propose a revision of current methods for Wolbachia supergroup typing.
      Transfer of whole wsp gene sequences between supergroups A and B has occurred.
      Furthermore, as a result of intragenic recombination, wsp phylogeny creates
      spurious basal lineages that are not supported by MLST. For example, the proposed
      supergroup G, based upon wsp alone, likely represents only a wsp recombinant
      clade. Removal of supergroup G is advised until and unless the existence of this
      lineage is substantiated by other sequence information (e.g., MLST). We recommend
      a full characterization MLST for a correct strain typing, while, based on the
      current data set, use of a single MLST gene can be effective for supergroup
      designation of A and B strains. Finally, we note that the sharing of wsp
      sequences between A and B strains indicates a strong genetic cohesiveness of
      Wolbachia strains, supporting designation of these bacteria within the same
      species, W. pipientis.

PMID- 17551787
TI  - Gene sequence phylogenies of the family microbacteriaceae.
AB  - The type strains of 32 species of 13 genera of the family Microbacteriaceae were
      analysed with respect to gene-coding phylogeny for DNA gyrase subunit B (gyrB),
      RNA-polymerase subunit B (rpoB), recombinase A (recA), and polyphosphate kinase
      (ppk). The resulting gene trees were compared with the 16S rRNA gene phylogeny of
      the same strains. The topology of neighbour-joining and maximum parsimony
      phylogenetic trees, based on nucleic-acid sequences and protein sequences of
      housekeeping genes, differed from one another, and no gene tree was identical to
      that of the 16S rRNA gene tree. Most genera analysed containing >1 strain formed
      phylogenetically coherent taxa. The three pathovars of Curtobacterium
      flaccumfaciens clustered together to the exclusion of the type strains of other
      Curtobacterium species in all DNA - and protein-based analyses. In no tree did
      the distribution of a major taxonomic marker, i.e., diaminobutyric acid versus
      lysine and/or ornithine in the peptidoglycan, or acyl type of peptidoglycan,
      correlate with the phylogenetic position of the organisms. The changing
      phylogenetic position of Agrococcus jenensis was unexpected: This strain defined
      individual lineages in the trees based on 16S rRNA and gyrB and showed identity
      with Microbacterium saperdae in the other three gene trees.

PMID- 17551788
TI  - Analysis of twin-arginine translocation pathway homologue in Staphylococcus
      aureus.
AB  - Staphylococcus aureus releases a large number of exoproteins, including membrane
      active proteins and toxins with superantigenic activity involved in
      pathogenicity. However, the export pathways of exoproteins in S. aureus have not
      been reported. We analyzed the function of the staphylococcal twin-arginine
      translocation (Tat) pathway homologue, the presence of which was recently
      discovered according to the genome database. The amino-acid sequences of the Tat
      homologues of S. aureus do not have a high similarity with those of Escherichia
      coli and other bacteria. Constructed tatC-deficient mutants from distinct parent
      strains showed the same patterns of exoproteins compared with those of parent
      strains on two-dementional gel electrophoresis, and the amounts of secreted
      staphylococcal enterotoxins and toxic shock syndrome toxin-1, of which signal
      peptides have some features often seen in signal sequences of Tat-dependent
      proteins, did not change with Western blotting analyses. Therefore, it seems that
      the Tat pathway does not play a major role in the secretion system of S. aureus,
      but other export pathways may play an important role in toxin secretion. This is
      the first experimental report showing the influence of the Tat pathway on the
      secretion of S. aureus.

PMID- 17551789
TI  - Molecular cloning, characterization, and expression of a chitinase from the
      entomopathogenic fungus Paecilomyces javanicus.
AB  - Paecilomyces javanicus is an entomopathogenic fungus of coleopteran and
      lepidopteran insects. Here we report on cloning, characterization, and expression
      patterns of a chitinase from P. javanicus. A strong chitinase activity was
      detected in P. javanicus cultures added to chitin. The full-length cDNA,
      designated PjChi-1, was cloned from mycelia by using both degenerate
      primer/reverse transcription polymerase chain reaction (RT-PCR) amplification and
      5'-/3'-RACE extension. The 1.18-kb cDNA gene contains a 1035-bp open reading
      frame and encodes a 345-amino acid polypeptide with a deduced molecular mass of
      37 kDa. A conserved motif for chitinase activity -F82DGIDIDWE90- was present in
      deduced amino acid sequence. Both RT-PCR and Northern analysis revealed that the
      expression of the PjChi gene was constitutive at low level, but enhanced to high
      level when chitin was the substrate. Fungal inhibitory assay showed that PjChi-1
      inhibited the growth of phytopathogenic fungi such as Sclerotium rolfsii,
      Colletotrichum gloeosporioides, Aspergillus nidulans, and Rhizoctonia solani.

PMID- 17551790
TI  - Effects of Ultraviolet Radiation on the Gram-positive marine bacterium
      Microbacterium maritypicum.
AB  - Although extensive information is available on the effect ultraviolet (UV)
      radiation has on Gram-negative marine bacteria, there is a scarcity of data
      concerning UV radiation and Gram-positive marine bacteria. The focus of this
      paper is on Microbacterium maritypicum, with the Gram-negative Vibrio natriegens
      being used as a standard of comparison. M. maritypicum exhibited growth over a
      NaCl range of 0-1000 mM: , with optimum growth occurring between 0 and 400 mM:
      NaCl. In contrast, V. natriegens grew over a NaCl span of 250-1000 mM: , with
      best growth being observed between 250 and 600 mM: NaCl. UV radiation experiments
      were done using the medium with 250 mM: NaCl. For solar (UV-A and B) radiation
      and log-phase cells, M. maritypicum was determined to be three times more
      resistant than V. natriegens. For germicidal (UV-C) radiation, the pattern of
      resistance of the log-phase cells to the lethal effects of the radiation was even
      more pronounced, with the Gram-positive bacterium being more than 12 to 13 times
      more resistant. Similar data to the solar and germicidal log-phase UV kill curves
      were obtained for stationary-phase cells of both organisms. Photoreactivation was
      observed for both types of cells exposed to UV-C but none for cells treated with
      UV-A and B. When log phase cells of M.maritypicum were grown at 0.0 and 0.6 M:
      NaCl and exposed to UV-C radiation, no difference in survivorship patterns was
      noted from that of 0.25 M: NaCl grown cells. Although this study has only focused
      on two marine bacteria, our results indicate that the Gram-positive M.
      maritypicum could have a built-in advantage for survival in some marine
      ecosystems.

PMID- 17551791
TI  - Nt mutation causing laterality defects associated with deletion of rotatin.
AB  - No turning (nt), a recessive lethal mutation causing left-right and axial
      patterning defects, was recovered in outbred CD-1 mice. Homozygous mutant embryos
      die at E11.5, exhibiting randomized heart tube looping and a failure to undergo
      embryonic turning. Previous studies showed notochordal defects associated with
      abnormal expression of HNF3beta, lefty, and nodal. To identify the genetic
      alteration underlying nt mutants, we intercrossed this mutation into a Mus
      musculus castaneus strain background and conducted a full-genome scan using
      polymorphic microsatellite DNA markers. We mapped the mutation to an 18-Mb
      interval in mouse chromosome 18, spanning marker D18mit189 and the distal end of
      the chromosome. RT-PCR analysis of known genes in the mapped interval showed no
      transcripts for four genes, including Rttn, CD226, Dok6, and Txndc10. Chromosome
      walking by serial PCR amplification of genomic DNA from homozygous mutants
      revealed a 1.6-Mb deletion spanning these four genes. A gene-trap mouse line with
      disruption of Rttn was previously also shown to have randomized heart tube
      looping, defects in embryonic turning, and abnormal expression of HNF3beta,
      lefty, and nodal. Together these findings suggest that nt is likely elicited by
      Rttn deficiency.

PMID- 17551792
TI  - Genome-wide search for microsatellite markers associated with radiologic
      alterations in the navicular bone of Hanoverian warmblood horses.
AB  - The aim of this study was to identify quantitative trait loci (QTLs) for
      pathologic changes in the navicular bone in Hanoverian warmblood horses.
      Seventeen paternal half-sib groups comprising 192 individuals were analyzed in a
      whole-genome scan. These families included 144 progeny and grandchildren, which
      were randomly chosen from the Hanoverian warmblood. Three different traits were
      considered: deformed canales sesamoidales and radiographic changes in the contour
      and in the structure of the navicular bone. The genome scan included in total 214
      highly polymorphic microsatellite markers. The putatively linked genomic regions
      on equine chromosomes (ECA) 2, 3, 10, and 15 were refined using 53 additional
      microsatellites. Chromosome-wide significant QTLs were located on five different
      equine chromosomes (ECA2, 3, 4, 10, and 26). Genome-wide significant QTLs were on
      ECA2 at 48 cM and on ECA10 from 45.5 to 49.8 cM. This study was a first step to
      get more insight into the molecular genetic determination of radiologic changes
      in the equine navicular bone.

PMID- 17551793
TI  - Effects of bolus consistency on timing and safety of swallow in patients with
      Parkinson's disease.
AB  - Aspiration pneumonia is the leading cause of death in Parkinson's disease (PD)
      patients. In clinical practice, the videofluoroscopic examination (VFE) is the
      most common method for evaluation of swallowing disorders. One of the variables
      manipulated during the VFE is consistency of the bolus. The results of this
      examination greatly influence the recommendations made by speech-language
      pathologists regarding swallow therapy and/or intervention. The primary aim of
      this study was to investigate the effects of bolus consistency on penetration
      aspiration (P-A) score and timing of swallow of persons with PD. The
      videoradiographic images of ten participants with PD swallowing six thin and six
      pudding-thick boluses were analyzed. Swallow timing and P-A were measured. (i.e.,
      oral transit time, pharyngeal transit time, number of tongue pumps, and P-A
      score). The results demonstrated various significant differences and
      relationships among the dependent variables. Implications for further research
      and clinical practice are discussed.

PMID- 17551794
TI  - Is final TNM staging a predictor for survival in locally advanced rectal cancer
      after preoperative chemoradiation therapy?
AB  - BACKGROUND: Neoadjuvant chemoradiation therapy has improved the local control
      rate and overall survival in locally advanced rectal cancers. The purpose of this
      retrospective study is to evaluate the correlation between the final pathologic
      stage and survival in these patients. METHODS: Patients with biopsy-proven rectal
      carcinoma, pretreatment staging by magnetic resonance imaging such as T3 or T4
      tumors, or node-positive disease were treated with preoperative concomitant 5
      fluorouracil-based chemotherapy and radiation, followed by radical surgical
      resection. Clinical outcome with survival, disease-free survival, recurrence
      rate, and local recurrence rate were compared with each T and N findings using
      the American Joint Committee on Cancer Tumor-Node-Metastasis (TNM) staging
      system. RESULTS: A total of 248 patients were enrolled in this study. Overall
      survival and disease-free survival at 1, 3, and 5 years were 97.1, 92, and 89.9%
      and 87.5, 71.1, and 69.5%, respectively. Thirty-six patients (14.5%) had a
      pathologic complete response after neoadjuvant therapy. The recurrence rate was
      significantly different between the pathologic complete response group and
      residual group (5.6 vs 31.1%; P = .002). Five-year disease-free survival was
      significantly better in the complete response group than the residual tumor group
      (93 vs 66%; P = .0045). There was no statistical difference in survival or
      locoregional recurrence rate between these two groups. CONCLUSIONS: Posttreatment
      pathologic TNM stage is correlated to disease-free survival and tumor recurrence
      rate in locally advanced rectal cancer after preoperative chemoradiation. Also,
      pathologic complete response to neoadjuvant treatment has its oncologic benefit
      in both overall recurrence and disease-free survival.

PMID- 17551795
TI  - Liver-directed surgery for metastatic squamous cell carcinoma to the liver:
      results of a multi-center analysis.
AB  - BACKGROUND: The role of hepatic resection for metastatic squamous cell carcinoma
      (SCC) remains unknown. The current study evaluates the role of hepatic resection
      in patients with metastatic SCC to the liver. METHODS: Between 1988 and 2006, 52
      patients underwent hepatic resection of metastatic SCC at eight major cancer
      centers. Clinicopathologic factors were analyzed with regard to disease-free
      survival (DFS) and overall survival (OS). RESULTS: Primary SCC site was anal (n =
      27), head/neck (n = 12), lung (n = 4), esophagus (n = 2), and other (n = 7).
      Treatment of primary SCC was chemotherapy +/- radiotherapy alone (n = 29),
      chemotherapy +/- radiotherapy + surgery (n = 15), or surgery alone (n = 8). Forty
      seven patients underwent resection alone, 2 resection + radiofrequency ablation
      (RFA), and 3 RFA only. At last follow-up, 33 (63.5%) patients had recurred. The
      median time to recurrence was 9.8 months, and 5-year DFS was 18.6%. Factors
      associated with reduced DFS were liver tumor size > 5 cm (hazard ratio (HR) =
      2.02) and positive surgical margin (HR = 2.33). The overall median survival after
      hepatic resection was 22.3 months and 5-year actuarial OS was 20.5%. Risk factors
      associated with worse overall survival included synchronous disease (HR = 4.09),
      hepatic metastasis > 5 cm (HR = 1.71) and positive surgical resection margin (HR
      = 1.83). CONCLUSIONS: The majority of patients will recur following hepatic
      resection of SCC. Long-term survival, however, can be achieved following surgical
      resection of SCC liver metastasis, especially in patients who present with
      limited metachronous disease amenable to margin negative resection.

PMID- 17551797
TI  - Innovations in education and clinical practice.

PMID- 17551796
TI  - Patient safety knowledge and its determinants in medical trainees.
AB  - BACKGROUND: Patient safety is a core educational topic for medical trainees.
      OBJECTIVES: To determine the current level and determinants of patient safety
      knowledge in medical trainees. DESIGN: Multi-institutional cross-sectional
      assessment of patient safety knowledge. PARTICIPANTS: Residents and medical
      students from seven Harvard-affiliated residencies and two Harvard Medical School
      courses. MEASUREMENTS: Participants were administered a 14-item validated test
      instrument developed based on the patient safety curriculum of the Risk
      Management Foundation (Cambridge, MA). The primary outcome measure was the amount
      of patient safety knowledge demonstrated by trainees on the validated test
      instrument. The secondary outcome measure was their subjective perceptions as to
      their baseline knowledge level in this domain. RESULTS: Ninety-two percent
      (640/693) of residents and medical students completed the patient safety test.
      Participants correctly answered a mean 58.4% of test items (SD 15.5%). Univariate
      analyses show that patient safety knowledge levels varied significantly by year
      of training (p = 0.001), degree program (p < 0.001), specialty (p < 0.001),
      country of medical school (p = 0.006), age (p < 0.001), and gender (p = 0.050);
      all but the latter two determinants remained statistically significant in
      multivariate models. In addition, trainees were unable to assess their own
      knowledge deficiencies in this domain. CONCLUSIONS: Patient safety knowledge is
      limited among medical trainees across a broad range of training levels, degrees,
      and specialties. Effective educational interventions that target deficiencies in
      patient safety knowledge are greatly needed.

PMID- 17551799
TI  - Screening for problem drinking : Comparison of CAGE and AUDIT.
AB  - OBJECTIVE: To compare self-administered versions of three questionnaires for
      detecting heavy and problem drinking: the CAGE, the Alcohol Use Disorders
      Identification Test (AUDIT), and an augmented version of the CAGE. DESIGN: Cross
      sectional surveys. SETTING: Three Department of Veterans Affairs general medical
      clinics. PATIENTS: Random sample of consenting male outpatients who consumed at
      least 5 drinks over the past year ("drinkers"). Heavy drinkers were oversampled.
      MEASUREMENTS: An augmented version of the CAGE was included in a questionnaire
      mailed to all patients. The AUDIT was subsequently mailed to "drinkers."
      Comparison standards, based on the tri-level World Health Organization alcohol
      consumption interview and the Diagnostic Interview Schedule, included heavy
      drinking (>14 drinks per week typically or >/=5 drinks per day at least monthly)
      and active DSM-IIIR alcohol abuse or dependence (positive diagnosis and at least
      one alcohol-related symptom in the past year). Areas under receiver operating
      characteristic curves (AUROCs) were used to compare screening questionnaires.
      MAIN RESULTS: Of 393 eligible patients, 261 (66%) returned the AUDIT and
      completed interviews. For detection of active alcohol abuse or dependence, the
      CAGE augmented with three more questions (AUROC 0.871) performed better than
      either the CAGE alone or AUDIT (AUROCs 0.820 and 0.777, respectively). For
      identification of heavy-drinking patients, however, the AUDIT performed best
      (AUROC 0.870). To identify both heavy drinking and active alcohol abuse or
      dependence, the augmented CAGE and AUDIT both performed well, but the AUDIT was
      superior (AUROC 0.861). CONCLUSIONS: For identification of patients with heavy
      drinking or active alcohol abuse or dependence, the self-administered AUDIT was
      superior to the CAGE in this population.

PMID- 17551800
TI  - Patient and physician roles in end-of-life decision making.
AB  - This study is a cross-sectional descriptive survey of randomly selected primary
      care patients and physicians regarding patient, physician, and family roles in
      end-of-life decision making. The subjects included 329 adult outpatients and 272
      practicing physicians. Physicians were more likely than patients to believe the
      patient alone was responsible for making end-of-life decisions. Patients were
      more likely than physicians to believe the physician should provide a
      recommendation in addition to facts to help the patient make end-of-life
      decisions. We conclude that patients prefer a more active role for physicians in
      both decision making and discussion of end-of-life care than do physicians
      themselves.

PMID- 17551808
TI  - Mesh repair for postoperative wound dehiscence in the presence of infection: is
      absorbable mesh safer than non-absorbable mesh?
AB  - OBJECTIVE: In patients with postoperative wound dehiscence in the presence of
      infection, extensive visceral oedema often necessitates mechanical containment of
      bowel. Prosthetic mesh is often used for this purpose. The aim of the present
      study was to assess the safety of the use of non-absorbable and absorbable meshes
      for this purpose. METHOD: All patients that had undergone mesh repair of
      abdominal wound dehiscence between January 1988 and January 1998 in the presence
      of intra-abdominal infection were included in a retrospective cohort study. All
      surviving patients had physical follow-up in February 2001. RESULT: Eighteen
      patients were included in the study. Meshes consisted of polyglactin (n = 6),
      polypropylene (n = 8), polyester (n = 1), or a combination of a polypropylene
      mesh with a polyglactin mesh on the visceral side (n = 3). All patients developed
      complications, consisting mainly of mesh infection (77%), intra-abdominal abscess
      (17%), enterocutaneous fistula (17%), or mesh migration through the bowel (11%).
      Mesh removal was necessary in eight patients (44%). Within four months
      postoperatively, six patients (33%) had died because of progressive abdominal
      sepsis. The incidence of progressive abdominal sepsis was significantly higher in
      the group with absorbable polyglactin mesh than in the group with nonabsorbable
      mesh (67 vs. 11%, p = 0.02) After a mean follow-up of 49 months, 63% of the
      surviving patients had developed incisional hernia. Absorbable meshes did not
      yield better outcomes than nonabsorbable meshes in terms of complications and
      mortality rate. CONCLUSION: Synthetic graft placement in the presence of intra
      abdominal infection has a high risk of complications, regardless of whether
      absorbable (polyglactin) or non-absorbable mesh material (polypropylene or
      polyester) is used, and should be avoided if possible.

PMID- 17551809
TI  - Sheddable coatings for long-circulating nanoparticles.
AB  - Nanoparticles, such as liposomes, polymeric micelles, lipoplexes and polyplexes
      are frequently studied as targeted drug carrier systems. The ability of these
      particles to circulate in the bloodstream for a prolonged period of time is often
      a prerequisite for successful targeted delivery. To achieve this, hydrophilic
      'stealth' polymers, such as poly(ethylene glycol) (PEG), are used as coating
      materials. Such polymers shield the particle surface and thereby reduce
      opsonization by blood proteins and uptake by macrophages of the mononuclear
      phagocyte system. Yet, after localizing in the pathological site, nanoparticles
      should deliver their contents in an efficient manner to achieve a sufficient
      therapeutic response. The polymer coating, however, may hinder drug release and
      target cell interaction and can therefore be an obstacle in the realization of
      the therapeutic response. Attempts have been made to enhance the therapeutic
      efficacy of sterically stabilized nanoparticles by means of shedding, i.e. a loss
      of the coating after arrival at the target site. Such an 'unmasking' process may
      facilitate drug release and/or target cell interaction processes. This review
      presents an overview of the literature regarding different shedding strategies
      that have been investigated for the preparation of sterically stabilized
      nanoparticulates. Detach mechanisms and stimuli that have been used are
      described.

PMID- 17551810
TI  - High sensitivity differential scanning calorimetry study of DNA-cationic liposome
      complexes.
AB  - PURPOSE: To investigate plasmid DNA interactions with liposomes prepared from
      dimyristoylglyceroethylphosphocholine (EDMPC) and DOPE using high sensitivity
      differential scanning calorimetry (HSDSC). MATERIALS AND METHODS: Large
      unilamellar liposomes of EDMPC with DOPE (mol ratio 0-50%) were prepared. Plasmid
      DNA was added to give a final DNA/lipid (-/+) charge ratio of 0.5. Samples were
      placed into an HSDSC and cooled to 3 degrees C, held isothermally for 30 min and
      then the temperature was ramped to 120 degrees C at a rate of 1 degree C/min.
      RESULTS: On heating EDMPC liposomes, the main phase transition occurred at 21.2
      degrees C, with a low temperature shoulder on the endothermic peak. At low DOPE
      concentrations the main phase transition temperatures and enthalpies of
      transition were lower than for pure EDMPC, with a peak corresponding to a pure
      EDMPC phase occurring at DOPE concentrations of 12-17 mol%. At 50 mol%, no main
      transition endotherm was observed. DNA solution produced two endothermic peaks
      with numerous 'satellite' peaks indicating thermal denaturation. DNA binding to
      EDMPC changed the shape of the thermogram, indicating alteration in lipid packing
      within the bilayer. DNA induced demixing in the bilayers of DOPE-containing
      liposomes. CONCLUSION: HSDSC provided information for characterizing liposome
      formulations and DNA interactions with such vesicles.

PMID- 17551811
TI  - Role of P-glycoprotein in limiting the brain penetration of glabridin, an active
      isoflavan from the root of Glycyrrhiza glabra.
AB  - PURPOSE: Glabridin is a major active constituent of Glycyrrhiza glabra which is
      commonly used in the treatment of cardiovascular and central nervous system (CNS)
      diseases. Recently, we have found that glabridin is a substrate of P-glycoprotein
      (PgP/MDR1). This study aimed to investigate the role of PgP in glabridin
      penetration across the blood-brain barrier (BBB) using several in vitro and in
      vivo models. MATERIALS AND METHODS: Cultured primary rat brain microvascular
      endothelial cells (RBMVECs) were used in the uptake, efflux and transcellular
      transport studies. A rat bilateral in situ brain perfusion model was used to
      investigate the brain distribution of glabridin. The brain and tissue
      distribution of glabridin in rats with or without coadministered verapamil or
      quinidine were examined with correction for the tissue residual blood. In
      addition, the brain distribution of glabridin in mdr1a(-/-) mice was compared
      with the wild-type mice. Glabridin in various biological matrices was determined
      by a validated liquid chromatography mass spectrometric method. RESULTS: The
      uptake and efflux of glabridin in cultured RBMVECs were ATP-dependent and
      significantly altered in the presence of a PgP or multi-drug resistance protein
      (Mrp1/2) inhibitor (e.g. verapamil or MK-571). A polarized transport of glabridin
      was found in RBMVEC monolayers with facilitated efflux from the abluminal (BL) to
      luminal (AP) side. Addition of a PgP or Mrp1/2 inhibitor in both luminal and
      abluminal sides attenuated the polarized transport across RBMVECs. In a bilateral
      in situ brain perfusion model, the uptake of glabridin into the cerebrum
      increased from 0.42 +/- 0.09% at 1 min to 9.27 +/- 1.69% (ml/100 g tissue) at 30
      min and was significantly greater than that for sucrose. Co-perfusion of a PgP or
      Mrp1/2 inhibitor significantly increased the brain distribution of glabridin by
      33.6-142.9%. The rat brain levels of glabridin were only about 27% of plasma
      levels when corrected by tissue residual blood and it was increased to up to 44%
      when verapamil or quinidine was coadministered. The area under the brain
      concentration-time curve (AUC) of glabridin in mdr1a(-/-) mice was 6.0-fold
      higher than the wild-type mice. CONCLUSIONS: These findings indicate that PgP
      limits the brain penetration of glabridin through the BBB and PgP may cause drug
      resistance to glabridin (licorice) therapy for CNS diseases and potential drug
      glabridin interactions. However, further studies are needed to explore the role
      of other drug transporters (e.g. Mrp1-4) in restricting the brain penetration of
      glabridin.

PMID- 17551812
TI  - Multiple depression : making mood manageable.
AB  - The subject of this paper is the problematisation of depression in today's mental
      health care. It is based on a study of the professional discussion on depression
      in Finland from the mid-1980s to the 1990s. The ways in which Finnish mental
      health experts define the object of depression treatment bring out an ambivalence
      that stems from the discrepancy between two parallel but incongruent notions of
      what depression is: the psychopharmacological and the psychotherapeutic. The
      analysis of the discussion demonstrates how clinical and practical rationales of
      today's mental health care are formed in the space between the two poles. Two
      tendencies of these rationales are also pointed out: first, the DSM paradigm of
      depressive illness inclines to become problematic and to dissolve in the actual
      practices. Second, they insinuate emphasis on antidepressant medication and
      overall neuropsychiatric approach in the treatment of depressive disorders,
      although in an ambivalent way.

PMID- 17551813
TI  - Medicine and music: three relations considered.
AB  - Two well-recognised, but inherently reductionist, relations between medicine and
      music are the attempted neuro-scientific understanding of responses to music and
      interest in music's contributions to clinical therapy. This paper proposes a
      third relation whereby music is seen as an organising metaphor for clinical
      medicine as a practice. Both music and clinical medicine affirm human well-being,
      and both do this inter alia through varieties of skilful, crafted yet spontaneous
      mutual engagement between a 'performer' and an 'audience'. I argue that this
      organising metaphor offers a corrective to the reductionist influences of the
      first two relations, illuminates a number of medicine's important features, and
      reaffirms the existential as being at the core of medicine's telos.

PMID- 17551814
TI  - The Warburg effect and its cancer therapeutic implications.
AB  - Increased aerobic glycolysis in cancer, a phenomenon known as the Warburg effect,
      has been observed in various tumor cells and represents a major biochemical
      alteration associated with malignant transformation. Although the exact molecular
      mechanisms underlying this metabolic change remain to be elucidated, the profound
      biochemical alteration in cancer cell energy metabolism provides exciting
      opportunities for the development of therapeutic strategies to preferentially
      kill cancer cells by targeting the glycolytic pathway. Several small molecules
      capable of inhibiting glycolysis in experimental systems have been shown to have
      promising anticancer activity in vitro and in vivo. This review article provides
      a brief summary of our current understanding of the Warburg effect, the
      underlying mechanisms, and its influence on the development of therapeutic
      strategies for cancer treatment.

PMID- 17551815
TI  - A pivotal role for p53: balancing aerobic respiration and glycolysis.
AB  - The genetic basis of increased glycolytic activity observed in cancer cells is
      likely to be the result of complex interactions of multiple regulatory pathways.
      Here we review the recent evidence of a simple genetic mechanism by which tumor
      suppressor p53 regulates mitochondrial respiration with secondary changes in
      glycolysis that are reminiscent of the Warburg effect. The biological
      significance of this regulation of the two major pathways of energy generation by
      p53 remains to be seen.

PMID- 17551816
TI  - HIF-1 mediates the Warburg effect in clear cell renal carcinoma.
AB  - Hypoxia-inducible factor 1 (HIF-1) is a transcription factor that functions as a
      master regulator of oxygen homeostasis in all metazoan species. O(2)-dependent
      hydroxylation of two proline residues in the HIF-1alpha subunit is necessary for
      the binding of the von Hippel-Lindau (VHL) protein, which is a component of a
      ubiquitin protein ligase that ubiquitinates HIF-1alpha, leading to its
      degradation by the proteasome. In the majority of cases of the clear cell type of
      renal carcinoma, both VHL genes are inactivated by mutation or epigenetic
      silencing, leading to dysregulated HIF-1 transcriptional activity. VHL loss-of
      function leads, under aerobic conditions, to a HIF-1-dependent reprogramming of
      glucose and energy metabolism that includes increased glucose uptake, glycolysis,
      and lactate production accompanied by a reciprocal decrease in respiration. These
      findings delineate for the first time the molecular mechanisms underlying the
      Warburg effect in a human cancer.

PMID- 17551817
TI  - Maternal smoking during pregnancy and birthweight: a propensity score matching
      approach.
AB  - There is accumulated evidence of the existence of a deleterious effect of smoking
      on birth outcomes. Understanding the effect of smoking on pregnancy is a critical
      issue because of the public policy implications for dissuading maternal smoking.
      We explore this issue by using the propensity score method and compare that with
      parametric estimators. First we estimate the treatment effect of smoking during
      pregnancy on different birth outcomes, by race. Then, we extend the method to the
      case of the multi-treatment "intensity of smoking." The deleterious effect of
      smoking is found robust to the different estimation methods used.

PMID- 17551818
TI  - Healthcare providers' satisfaction with a State Children's Health Insurance
      Program (SCHIP).
AB  - PURPOSE: This study's purpose was to understand how experiences with and
      perceptions of the health care plan characteristics influence provider
      satisfaction with a State Children's Health Insurance Program (SCHIP). METHODS:
      Physicians and other health care providers participating in one program (ALL
      Kids) were mailed a survey (n = 500). Pediatricians were the most likely to
      return the survey. We used frequencies, chi-square and logistic regression
      analysis to explore relationships. RESULTS: The odds of being less satisfied with
      the program among providers who perceived that reimbursement in the ALL Kids
      program was less compared to private insurance were almost 7 times (OR = 6.81;
      95% CI = (1.88-24.73)) greater than for those who perceived that reimbursement
      was more or the same in ALL Kids. Likewise, respondents who perceived that All
      Kids families were less likely than families with private insurance to return for
      follow-up visits were less satisfied with ALL Kids (OR = 17.42; 95% CI = (1.85
      164.70)). CONCLUSIONS: The stigma of SCHIP may be less than that often associated
      with Medicaid; however, this investigation should be considered with others that
      have identified barriers for provider's participation. This study indicates that
      provider satisfaction is related to their perceptions of SCHIP policies and
      families, though it does not tell us what factors might contribute to this
      perception, such as, previous experience with public insurance (Medicaid) and
      publicly insured patients. Increasing reimbursement rates may not address
      perceptions that affect provider views of publicly-supported health plans and the
      participating families.

PMID- 17551819
TI  - Is there a role for the family and close community to help reduce the risk of
      postpartum depression in new mothers? A cross-sectional study of Turkish women.
AB  - OBJECTIVES: Postpartum depression is an important and under-diagnosed problem.
      The aims of this study were (1) to compare the prevalence of depressive
      symptomology in Turkish mothers who were 1-3 months postpartum with the
      prevalence of depressive symptomology in mothers who had not been pregnant for at
      least 1 year, (2) to identify risk factors associated with depression in both
      groups, and (3) to examine the effect of postpartum depression on breastfeeding
      by the mothers. DESIGN: Cross-sectional study SETTING: Well-baby clinic
      PARTICIPANTS: 326 women enrolled in January 2001; 163 were 1-3 months postpartum,
      and 163 had not been pregnant in the previous year. RESULTS: The prevalence of
      depressive symptomology in the postpartum and non-postpartum groups was 17%
      (28/163) and 24.5% (40/163), respectively; this was not statistically significant
      (P = 0.102). When we compared mean Beck Depression Inventory (BDI) scores, the
      difference between the two groups was statistically significant (10.75 +/- 8.06
      and 12.63 +/- 8.81, respectively, P = 0.045). Premenstrual tension and a history
      of depression were risk factors for depressive symptomology in both groups. Three
      or more births and a history of induced abortion were risk factors for depressive
      symptomology in the non-postpartum group. In the postpartum group, the effect of
      depression on breast-feeding was not statistically significant (P = 0.7). The
      generalisability of the study results to the community is limited. CONCLUSION: In
      this study, the prevalence of depressive symptomology in the postpartum and non
      postpartum groups did not show a significant difference, but the prevalence of
      depressive symptomology was high in both groups. Postpartum depression did not
      have a negative effect on breast-feeding. Lower BDI scores in the postpartum
      period may be the result of the protective factors of motherhood which is a
      respected status for women in populations where the preservations of traditions
      and customs are valued.

PMID- 17551820
TI  - Khat (Catha edulis) chewing during pregnancy in Yemen: findings from a national
      population survey.
AB  - AIMS: This study examines the prevalence of khat chewing among women during
      pregnancy and some of the risk factors for this habit in Yemen. METHODS: Survey
      data on 7,343 ever-married women from the Yemen Demographic and Maternal and
      Health Survey (YDMHS), conducted in 1997 are used. Women who had a live birth
      during the 5 years preceding the survey were asked if they chewed khat during
      each of their pregnancies (=1) or not (=0). Associations between chewing khat and
      socio-demographic risk factors were assessed using odds ratios from binary
      logistic regression models. RESULTS: About 40.7% of women surveyed reported
      chewing khat while pregnant during the 5 years before the survey. Old age, no
      education, rural residence, living in mountainous regions, and low wealth were
      significant risk factors for chewing khat. CONCLUSIONS: Khat chewing during
      pregnancy is highly prevalent in Yemen. Socio-economically disadvantaged women
      were more likely to chew khat than other women.

PMID- 17551821
TI  - The body mass index of teen mothers and their toddler children.
AB  - OBJECTIVES: To evaluate: change in Body Mass Index (BMI) of adolescent mothers
      (14-19 years of age) from pre-pregnancy to 36 months postpartum; BMI of their
      children age 2 or older; relationship between maternal BMI and children's BMI.
      METHODS: Retrospective medical record abstraction of adolescent mothers attending
      a medical program in Massachusetts between 2001 and 2005 who had self-reported
      pre-pregnancy BMI data at first prenatal visit, at least one BMI measure 12 or
      more months postpartum, and who did not experience a repeat pregnancy (n = 52).
      Children of adolescent mothers were included if they had received their 2 (n =
      41) and/or 3 (n = 28) year physical. RESULTS: Adolescent mothers: overweight
      increased from 25% pre-pregnancy to 33% at 24-36 months postpartum; obesity more
      than doubled in the same time period, from 15% to 36%. Those with BMI data
      available pre-pregnancy and postpartum had an increase in mean BMI from 25 pre
      pregnancy to 29 at 24-36 months postpartum (P < 0.001). Two-year-old children:
      About 5% were at risk for overweight and 12% were overweight. Three-year-old
      children: About 18% were at risk for overweight and 18% were overweight. When BMI
      categories of children were compared to BMI categories of their mothers, there
      was a trend for adolescent mothers with overweight/obesity at 24-36 months
      postpartum to have 3-year-old children at risk for overweight or overweight (P =
      0.092). CONCLUSIONS: There was a significant increase in overweight/obesity in
      this cohort of adolescent mothers and their children followed 36 months
      postpartum. The long-term sequelae of overweight/obesity indicates a need for
      effective interventions.

PMID- 17551822
TI  - The associations between inter-pregnancy interval and maternal and neonatal
      outcomes in Brazil.
AB  - OBJECTIVES: Global estimates of maternal and perinatal mortality have remained
      unchanged over the past 20 years, and strategies are being sought to decrease the
      occurrence of maternal and perinatal death. The objective of this study was to
      evaluate the association between inter-pregnancy interval and the occurrence of
      adverse maternal and perinatal outcomes. METHODS:  DESIGN AND SETTING: Cross
      sectional study of the obstetrical and perinatal records in an intra-hospital
      obstetrics database between 1986 and 2000 at a tertiary maternity hospital in
      Brazil. PARTICIPANTS: A total of 14,930 records of parous women who delivered
      singleton infants. MAIN OUTCOME MEASURES: Crude and adjusted odds ratio estimates
      of gestational outcome according to inter-pregnancy intervals. RESULTS: During
      the period of the study, 34.6% of records referred to women with an inter
      pregnancy interval <18 months. After the adjustment performed for 11 confounding
      factors and assuming an inter-pregnancy interval of 18-23 months as reference,
      short intervals (<6 months) were observed to be associated with a greater risk of
      low birth weight (odds ratio: 1.74; 95% confidence interval: 1.18-2.55), and
      preterm birth (1.56; 1.01-2.46). On the other hand, long intervals were
      significantly associated with fewer C-sections (0.69; 0.56-0.82), and a greater
      risk of premature rupture of membranes (PROM) (1.57; 1.20-2.06) and low birth
      weight (1.46; 1.03-2.06). CONCLUSIONS: Short inter-pregnancy intervals are
      associated with a higher risk of low birth weight and preterm birth, while long
      intervals are associated with a higher risk of PROM, low birth weight and a lower
      risk of C-section.

PMID- 17551825
TI  - Housing status and associated differences in HIV risk behaviors among young
      injection drug users (IDUs).
AB  - Using cross-sectional analysis we examined residential status and associated
      differences in HIV risk behaviors among 3266 young IDUs enrolled in an HIV
      prevention trial. A three-level outcome (homeless (37%), equivocally housed
      (17%), housed (46%)) was defined based on responses to two questions assessing
      subjective and objective criteria for homelessness: "equivocally housed"
      participants were discordant on these measures. In multivariate analysis,
      antecedents of homelessness were having lived in an out-of-home placement, been
      thrown out of the home or in juvenile detention, and experienced childhood abuse;
      while correlates included receiving income from other and illegal sources,
      drinking alcohol or using methamphetamine at least daily, using shooting
      galleries, backloading, and sex work. A subset of these variables was associated
      with being equivocally housed. HIV risk varies by housing status, with homeless
      IDUs at highest risk. Programs for IDUs should utilize a more specific definition
      of residential status to target IDUs needing intervention.

PMID- 17551826
TI  - Phylogeography of wild musk shrew (Suncus murinus) populations in Asia based on
      blood protein/enzyme variation.
AB  - The musk shrew (Suncus murinus) is an insectivore species that inhabits tropical
      and subtropical Asia widely. To clarify the genetic relationship among wild musk
      shrew populations, we examined the electrophoretic variants of biparentally
      inherited genetic markers at 10 loci coding for eight blood proteins/enzymes in a
      total of 639 animals and compared the results obtained from the mitochondrial DNA
      data. The principal-component analysis performed using the allele frequency data
      revealed that the 17 populations could be divided into two major groups, a South
      Asian group and a Southeast Asian group that includes several island populations
      bound by Myanmar. The degrees of genetic divergence among populations were higher
      within the Southeast Asian group than within the South Asian group. This finding
      was incongruent with the mtDNA diversity. Analysis conducted at the individual
      level showed that a shrew from the central region in Myanmar that carries a South
      Asian type of mtDNA showed the electrophoretic variants specific to the Southeast
      Asian group, suggesting that this region is a contact zone between the two major
      groups.

PMID- 17551827
TI  - Isolation and characterization of a beta-tubulin gene from Trichoderma harzianum.

PMID- 17551828
TI  - Monoamine oxidases: from tissue homogenates to transgenic mice.
AB  - The regulation, structure and function of monoamine oxidases (MAO's) have been a
      subject of my research for many years. Studies of the enzyme have moved from
      early biochemical experiments, where different forms were biochemically
      characterized, to the molecular biology revolution where the genes for MAO A and
      MAO B were cloned and sequenced. Analyses of the signal pathways of gene
      regulation and specific transcriptional repression of MAO gene expression
      followed, as did the elucidation of the role of MAO in apoptosis. And
      importantly, MAO's impact on behavioral states of both mice and human beings was
      discovered. It is fulfilling and humbling to see how our early experiments with
      tissue homogenates and MAO A and MAO B gene cloning built a foundation for so
      much subsequent understanding of the molecular and genetic components underlying
      certain behaviors.

PMID- 17551829
TI  - Glia maturation factor regulation of STAT expression: a novel mechanism in
      experimental autoimmune encephalomyelitis.
AB  - Inflammatory cytokines are implemented in the pathogenesis of experimental
      autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. We
      previously demonstrated that glia maturation factor (GMF), a brain protein,
      isolated, sequenced and cloned in our laboratory, induce expression of
      proinflammatory cytokine/chemokine in the central nervous system (CNS). We found
      GMF-deficient (knockout) mice relatively resistant to EAE development after
      immunization with encephalitogenic MOG peptide 35-55. Consistent with these
      findings, the expression of proinflammatory cytokines in CNS of mice with EAE
      differed profoundly between wild type and GMF-knockout mice. In the present study
      we examined the expressions of six murine signal transducers and activators of
      transcription (STATs) genes, which are known to regulate the cytokine-dependent
      signal transduction pathways in autoimmune inflammation. The expressions of STATs
      genes were evaluated in the brains and spinal cords of wild type and GMF-knockout
      mice at the peak of EAE by quantitative real-time RT-PCR. Compared to GMF
      knockout mice, the expressions of STAT1, STAT2, STAT3, STAT4, STAT5, and STAT6
      genes were significantly (P < 0.001) upregulated in the wild type mice exhibiting
      EAE symptoms. The results are consistent with the diminished development of EAE
      in the GMF-knockout mice. A significant suppression of STATs expression in GMF
      knockout mice suggests GMF as an upstream effector of JAK/STAT signaling.

PMID- 17551830
TI  - The role of nitric oxide in the neuroprotection of limb ischemic preconditioning
      in rats.
AB  - Brief limb ischemia was reported to protect neurons against injury induced by
      subsequent cerebral ischemia-reperfusion, and this phenomenon is known as limb
      ischemic preconditioning (LIP). To explore the role of nitric oxide (NO) in
      neuroprotection of LIP in rats, we observed changes in the content of nitric
      oxide (NO) and activity of NO synthase (NOS) in the serum and CA1 hippocampus of
      rats after transient limb ischemic preconditioning (LIP), and the influence of
      N(G)-nitro-L-arginine methylester (L-NAME), a NOS inhibitor, on the
      neuroprotection of LIP against cerebral ischemia-reperfusion injury. Results
      showed that NO content and NOS activity in serum increased significantly after
      LIP compared with the sham group. The increase showed a double peak pattern, in
      which the first one appeared at time 0 (immediate time point) and the second one
      appeared at 48 h after the LIP (P < 0.01). The NO content and NOS activity in the
      CA1 hippocampus in LIP group showed similar change pattern with the changes in
      the serum, except for the first peak of up-regulation of NO content and NOS
      activity appeared at 6 h after LIP. Pretreatment with L-NAME before LIP blocked
      the neuroprotection of LIP against subsequent cerebral ischemic insult. The
      blocking effect of L-NAME was abolished with pretreatment of L-Arg. These
      findings indicated that NO may be associated with the tolerance of pyramidal
      cells in the CA1 hippocampus to ischemia induced by LIP in rats.

PMID- 17551831
TI  - Docosahexaenoic acid enhances iron uptake by modulating iron transporters and
      accelerates apoptotic death in PC12 cells.
AB  - The effect of docosahexaenoic acid (DHA; 22:6 n-3) on Fe(2+)-mediated and/or
      H(2)O(2)-mediated oxidative stress (OS) was investigated in a PC12
      pheochromocytoma cell line in the presence or absence of 50 ng/ml nerve growth
      factor (NGF). DHA-supplemented cells showed enhanced Fe(2+)-induced cell damage
      as evident by increased lipid peroxides formation (10-fold) and reduced neutral
      red (NR) dye uptake in a NGF-independent fashion. DHA caused a nearly 10-fold
      increase in free iron uptake in NGF-treated cells and doubled iron uptake in
      nondifferentiated cells. DHA-enrichment induced an elevation in the transferrin
      receptor protein in the nondifferentiated cells whereas NGF-treatment led to a
      substantial increase in the ubiquitous divalent metal ion transporter 1 (DMT-1)
      as detected by mRNA levels using qRT-PCR. The mechanism of action of DHA to
      accelerate cell death may be associated with the externalization of amino
      phosphoglycerides (PG) species of which, increased ethanolamine plasmalogen
      levels, may be essential for cell rescue as noted in NGF-treated PC12 cells.

PMID- 17551832
TI  - Lipid peroxidation scavengers prevent the carbonylation of cytoskeletal brain
      proteins induced by glutathione depletion.
AB  - In this study, we investigated the possible link between lipid peroxidation (LPO)
      and the formation of protein carbonyls (PCOs) during depletion of brain
      glutathione (GSH). To this end, rat brain slices were incubated with the GSH
      depletor diethyl maleate (DEM) in the absence or presence of classical LPO
      scavengers: trolox, caffeic acid phenethyl ester (CAPE), and butylated
      hydroxytoluene (BHT). All three scavengers reduced DEM-induced lipid oxidation
      and protein carbonylation, suggesting that intermediates/products of the LPO
      pathway such as lipid hydroperoxides, 4-hydroxynonenal and/or malondialdehyde are
      involved in the process. Additional in vitro experiments revealed that, among
      these products, lipid hydroperoxides are most likely responsible for protein
      oxidation. Interestingly, BHT prevented the carbonylation of cytoskeletal
      proteins but not that of soluble proteins, suggesting the existence of different
      mechanisms of PCO formation during GSH depletion. In pull-down experiments, beta
      actin and alpha/beta-tubulin were identified as major carbonylation targets
      during GSH depletion, although other cytoskeletal proteins such as neurofilament
      proteins and glial fibrillary acidic protein were also carbonylated. These
      findings may be important in the context of neurological disorders that exhibit
      decreased GSH levels and increased protein carbonylation such as Parkinson's
      disease, Alzheimer's disease, and multiple sclerosis.

PMID- 17551833
TI  - The pivotal role of astrocytes in the metabolism of iron in the brain.
AB  - Iron is essential for the normal functioning of cells but since it is also
      capable of generating toxic reactive oxygen species, the metabolism of iron is
      tightly regulated. The present article advances the view that astrocytes are
      largely responsible for distributing iron in the brain. Capillary endothelial
      cells are separated from the neuropil by the endfeet of astrocytes, so astrocytes
      are ideally positioned to regulate the transport of iron to other brain cells and
      to protect them if iron breaches the blood-brain barrier. Astrocytes do not
      appear to have a high metabolic requirement for iron yet they possess
      transporters for transferrin, haemin and non-transferrin-bound iron. They store
      iron efficiently in ferritin and can export iron by a mechanism that involves
      ferroportin and ceruloplasmin. Since astrocytes are a common site of abnormal
      iron accumulation in ageing and neurodegenerative disorders, they may represent a
      new therapeutic target for the treatment of iron-mediated oxidative stress.

PMID- 17551834
TI  - Differentiation of the roles of sulfide oxidase and rhodanese in the
      detoxification of sulfide by the colonic mucosa.
AB  - PURPOSE: Identify the roles of sulfide oxidase and rhodanese in sulfide
      detoxification in rat colonic mucosa. RESULTS: Gel filtration of colonic mucosa
      and purified bovine rhodanese showed that rhodanese and sulfide oxidizing
      activities resided in different proteins. In the presence of cyanide, rhodanese
      shifted the major mucosal metabolite of sulfide from thiosulfate to thiocyanate.
      The purported ability of purified rhodanese to metabolize sulfide reflects: (a)
      contamination with a sulfide oxidase, and (b) the spontaneous conversion of
      sulfide to thiosulfate during storage; rhodanese then catalyzes the conversion of
      this thiosulfate to thiocyanate. CONCLUSIONS: Rhodanese does not metabolize
      sulfide. The rate-limiting step in sulfide detoxification is oxidation by a
      sulfide oxidase to thiosulfate. Rhodanese then converts this thiosulfate to
      thiocyanate, but this reaction does not increase the rate of sulfide
      detoxification. The recent use of rhodanese activity as a surrogate for the rate
      that colonic mucosa detoxifies sulfide is inappropriate.

PMID- 17551835
TI  - Bowman-Birk inhibitor concentrate: a novel therapeutic agent for patients with
      active ulcerative colitis.
AB  - Bowman-Birk inhibitor concentrate (BBIC), a soy extract with high protease
      inhibitor activity, is efficacious in the treatment of colitis in mice and has
      been used in numerous clinical trials. A randomized, double blind, placebo
      controlled trial was performed to investigate the safety and possible benefits of
      BBIC in patients with active ulcerative colitis. The Sutherland Disease Activity
      Index (SDAI) was used to assess disease activity, response (Index decrease > or =
      3), and remission (Index < or = 1 with no rectal bleeding) in patients receiving
      12 weeks of therapy. The Index scores of patients receiving BBIC decreased more
      than those of the patients receiving placebo (P = 0.067). Beneficial trends were
      observed in the rates of remission (P = 0.082) and clinical response (P = 0.22).
      No severe adverse events were observed. This trial suggests a potential benefit
      over placebo for both achieving clinical response and induction of remission in
      patients with active ulcerative colitis without apparent toxicity.

PMID- 17551836
TI  - Family contact and housing stability in a national multi-site cohort of homeless
      adults with severe mental illness.
AB  - This study examined associations between family contact and housing stability
      among 4,778 homeless persons with mental illness who received intensive outreach
      and case management services through the national multi-site ACCESS project.
      Ordinary-least squares regression analysis found that, at 12-months post-study
      entry, greater contact with relatives to whom participants feel close, more
      frequent telephone contact, and greater satisfaction with family relationships
      were associated with a greater number of nights in stable housing. Program and
      policy implications for strengthening family ties as a means to reduce
      homelessness among this population are discussed.

PMID- 17551837
TI  - Sober housing and motivational interviewing: the Treatment Access Project.
AB  - This paper describes an innovative program that provides rental subsidies for
      sober housing and supportive services to persons in early recovery who are
      homeless and have substance use disorders. Preliminary data point to the success
      of this program in enhancing recovery and exiting from homelessness. In
      supporting sober house placements, the Treatment Access Project creates a bridge
      that supports these individuals in their transition from clinical treatment
      services to the community. Integration with natural community supports can help
      to build self-efficacy, which can enhance the likelihood that this population
      will obtain and maintain abstinence, gainful employment, and permanent housing.

PMID- 17551838
TI  - Mitochondrion-mediated apoptosis induced by Rana grylio virus infection in fish
      cells.
AB  - A fish cell line, fathead minnow (FHM) cell, was used to investigate the
      alteration of mitochondrial dynamics and the mechanism of apoptosis under Rana
      grylio virus (RGV) infection. Microscopy observations, flow-cytometry analysis
      and molecular marker detection revealed the apoptotic fate of the RGV-infected
      cells. Some typical apoptotic characteristics, such as chromatin condensation,
      DNA fragmentation and mitochondrial fragmentation, were observed, and
      significantly morphological changes of mitochondria, including size, shape,
      internal structure and distribution, were revealed. The mitochondria in RGV
      infected cells were aggregated around the viromatrix, and the aggregation could
      be blocked by colchicine. Moreover, the Deltapsim collapse was induced, and
      caspase-9 and caspase-3 were activated in the RGV-infected cells. In addition, NF
      kappaB activation and intracellular Ca(2+) increase were also detected at
      different times after infection. The data revealed the detailed dynamics of
      mitochondrion-mediated apoptosis induced by an iridovirus, and provided the first
      report on mitochondrial fragmentation during virus-induced apoptosis in fish
      cells.

PMID- 17551839
TI  - Indoor environmental differences between inner city and suburban homes of
      children with asthma.
AB  - We conducted this study to compare environmental exposures in suburban homes of
      children with asthma to exposures in inner city homes of children with asthma, to
      better understand important differences of indoor pollutant exposure that might
      contribute to increased asthma morbidity in the inner city. Indoor PM(10),
      PM(2.5), NO(2), O(3), and airborne and dust allergen levels were measured in the
      homes of 120 children with asthma, 100 living in inner city Baltimore and 20
      living in the surrounding counties. Home conditions and health outcome measures
      were also compared. The inner city and suburban homes differed in ways that might
      affect airborne environmental exposures. The inner city homes had more cigarette
      smoking (67% vs. 5%, p < .001), signs of disrepair (77% vs. 5%, p < .001), and
      cockroach (64% vs. 0%, p < .001) and mouse (80% vs. 5%, p < .001) infestation.
      The inner city homes had higher geometric mean (GM) levels (p < .001) of PM(10)
      (47 vs. 18 microg/m(3)), PM(2.5) (34 vs. 8.7 microg/m(3)), NO(2) [19 ppb vs.
      below detection (BD)], and O(3) (1.9 vs. .015 ppb) than suburban homes. The inner
      city homes had lower GM bedroom dust allergen levels of dust mite (.29 vs. 1.2
      microg/g, p = .022), dog (.38 vs. 5.5 microg/g, p < .001) and cat (.75 vs. 2.4
      microg/g, p = .039), but higher levels of mouse (3.2 vs. .013 microg/g, p < .001)
      and cockroach (4.5 vs. .42 U/g, p < .001). The inner city homes also had higher
      GM airborne mouse allergen levels (.055 vs. .016 ng/m(3), p = .002). Compared
      with the homes of suburban children with asthma, the homes of inner city
      Baltimore children with asthma had higher levels of airborne pollutants and home
      characteristics that predispose to greater asthma morbidity.

PMID- 17551840
TI  - Let's not ignore a growing HIV problem for Asians and Pacific Islanders in the
      U.S.
AB  - Recent analyses reported in the Morbidity and Mortality Weekly Report (MMWR) show
      that among all racial groups in the U.S., Asians and Pacific Islanders (APIs) had
      the only statistically significant increases in HIV/AIDS diagnosis rates in the
      most recent four-year period. Yet this fact is not noted in the discussion or
      editorial notes in the MMWR issue where this information is reported. Because HIV
      rates in API communities are still relatively low, we have a critical opportunity
      to develop effective prevention programs for API American communities before
      these alarming indicators translate into markedly higher HIV prevalence in API
      communities in the U.S., as has occurred in other U.S. communities and in the
      Asia/Pacific region.

PMID- 17551841
TI  - Quality of water the slum dwellers use: the case of a Kenyan slum.
AB  - As a result of rapid urbanization in a context of economic constraints, the
      majority of urban residents in sub-Saharan Africa live in slums often
      characterized by a lack of basic services such as water and sewerage.
      Consequently, the urban poor often use inexpensive pit latrines and at the same
      time may draw domestic water from nearby wells. Overcrowding in slums limits the
      adequate distance between wells and pit latrines so that micro-organisms migrate
      from latrines to water sources. Sanitary practices in these overcrowded slums are
      also poor, leading to contamination of these wells. This study sought to assess
      sanitary practices of residents of a Kenyan urban slum and fecal contamination of
      their domestic water sources. This cross-sectional study involved 192 respondents
      from Langas slum, Kenya. Forty water samples were collected from the water
      sources used by the respondents for laboratory analysis of coliforms. Of these 40
      samples, 31 were from shallow wells, four from deep wells, and five from taps.
      Multiple-tube fermentation technique was used to enumerate coliform bacteria in
      water. The study found that most people (91%) in the Langas slum used wells as
      the main source of domestic water, whereas the rest used tap water. Whereas most
      people used pit latrines for excreta disposal, a substantial percentage (30%) of
      children excreted in the open field. The estimated distance between the pit
      latrines and the wells was generally short with about 40% of the pit latrines
      being less than 15 m from the wells. The main domestic water sources were found
      to be highly contaminated with fecal matter. Total coliforms were found in 100%
      of water samples from shallow wells, while 97% of these samples from shallow
      wells were positive for thermotolerant coliforms. Three out of the four samples
      from deep wells were positive for total coliforms, while two of the four samples
      were positive for thermotolerant coliforms. None of the samples from taps were
      positive for either total or thermotolerant coliforms. Because the presence of
      thermotolerant coliforms in water indicates fecal contamination, facilitated by
      the proximity between the wells and pit latrines, the study suggests that the pit
      latrines were a major source of contamination of the wells with fecal matter.
      However, contamination through surface runoff during rains is also plausible as
      indiscriminate excreta disposal particularly by children was also common. Owing
      to the fecal contamination, there is a high possibility of the presence of
      disease pathogens in the water; thus, the water from the wells in Langas may not
      be suitable for human consumption. To address this problem, treatment of the
      water at community or household level and intensive behavioral change in sanitary
      practices are recommended. Efforts should be made to provide regulated tap water
      to this community and to other slums in sub-Saharan Africa where tap water is not
      accessible. However, more sampling of different water sources is recommended.

PMID- 17551842
TI  - Low rates of homogenization of the DBC-150 satellite DNA family restricted to a
      single pair of microchromosomes in species from the Drosophila buzzatii cluster.
AB  - A satellite DNA family, termed DBC-150, comprises slightly GC-rich repeat units
      of approximately 150 bp that were isolated (by DNA digestions or PCR) from the
      genome of all seven Drosophila species from the buzzatii cluster (repleta group).
      The presence of subrepeats suggests that part of the extant DBC-150 monomer
      originated by the duplication of small sequence motifs. The DBC-150 family is
      compared to the previously described pBuM satDNA family, an abundant component of
      the genome of five species of the cluster. The two families are different in
      several aspects, including primary structure, A + T content, intraspecific and
      interspecific variability and rates of homogenization (or nucleotide spread). The
      data indicate a lower rate of homogenization (and absence of complete concerted
      evolution) of the DBC-150 compared to the pBuM family. FISH on metaphase
      chromosomes revealed that the DBC-150 family is located exclusively in the
      microchromosomes. To our knowledge this is the first record of a complex
      Drosophila satDNA restricted to a single pair of microchromosomes. The observed
      low rates of homogenization of the DBC-150 family might be related to a presumed
      reduction or suppression of meiotic recombination in the microchromosomes.

PMID- 17551843
TI  - EPR spectroscopy of the manganese cluster of photosystem II.
AB  - Electron paramagnetic resonance (EPR) spectroscopy is a valuable tool for
      understanding the oxidation state and chemical environment of the Mn4Ca cluster
      of photosystem II. Since the discovery of the multiline signal from the S2 state,
      EPR spectroscopy has continued to reveal details about the catalytic center of
      oxygen evolution. At present EPR signals from nearly all of the S-states of the
      Mn4Ca cluster, as well as from modified and intermediate states, have been
      observed. This review article describes the various EPR signals obtained from the
      Mn4Ca cluster, including the metalloradical signals due to interaction of the
      cluster with a nearby organic radical.

PMID- 17551844
TI  - The carboxyl-terminal processing of precursor D1 protein of the photosystem II
      reaction center.
AB  - The D1 protein, a key subunit of photosystem II reaction center, is synthesized
      as a precursor form with a carboxyl-terminal extension, in oxygenic
      photosynthetic organisms with some exceptions. This part of the protein is
      removed by the action of an endopeptidase, and the proteolytic processing is
      indispensable for the manifestation of oxygen-evolving activity in
      photosynthesis. The carboxyl-terminus of mature D1 protein, which appears upon
      the cleavage, has recently been demonstrated to be a ligand for a manganese atom
      in the Mn(4)Ca-cluster, which is responsible for the water oxidation chemistry in
      photosystem II, based on the isotope-edited Fourier transform infrared
      spectroscopy and the X-ray crystallography. On the other hand, the structure of a
      peptidase involved in the cleavage of precursor D1 protein has been resolved at a
      higher resolution, and the enzyme-substrate interactions have extensively been
      analyzed both in vivo and in vitro. The present article briefly summarizes the
      history of research and the present state of our knowledge on the carboxyl
      terminal processing of precursor D1 protein in the photosystem II reaction
      center.

PMID- 17551845
TI  - Analysis of donors of electrons to photosystem I and cyclic electron flow by
      redox kinetics of P700 in chloroplasts of isolated bundle sheath strands of
      maize.
AB  - Bundle sheath chloroplasts of NADP-malic enzyme (NADP-ME) type C4 species have a
      high demand for ATP, while being deficient in linear electron flow and oxidation
      of water by photosystem II (PSII). To evaluate electron donors to photosystem I
      (PSI) and possible pathways of cyclic electron flow (CEF1) in isolated bundle
      sheath strands of maize (Zea mays L.), an NADP-ME species, light-induced redox
      kinetics of the reaction center chlorophyll of PSI (P700) were followed under
      aerobic conditions. Donors of electrons to CEF1 are needed to compensate for
      electrons lost from the cycle. When stromal electron donors to CEF1 are generated
      during pre-illumination with actinic light (AL), they retard the subsequent rate
      of oxidation of P700 by far-red light. Ascorbate was more effective than malate
      in generating stromal electron donors by AL. The generation of stromal donors by
      ascorbate was inhibited by DCMU, showing ascorbate donates electrons to the
      oxidizing side of PSII. The inhibitors of NADPH dehydrogenase (NDH), amytal and
      rotenone, accelerated the oxidation rate of P700 by far-red light after AL,
      indicating donation of electrons to the intersystem from stromal donors via NDH.
      These inhibitors, however, did not affect the steady-state level of P700+ under
      AL, which represents a balance of input and output of electrons in P700. In
      contrast, antimycin A, the inhibitor of the ferredoxin-plastoquinone reductase
      dependent CEF1, substantially lowered the level of P700+ under AL. Thus, the
      primary pathway of ATP generation by CEF1 may be through ferredoxin
      plastoquinone, while function of CEF1 via NDH may be restricted by low levels of
      ferredoxin-NADP reductase. NDH may contribute to redox poising of CEF1, or
      function to generate ATP in linear electron flow to O2 via PSI, utilizing NADPH
      generated from malate by chloroplastic NADP-ME.

PMID- 17551846
TI  - Good response in a patient with deep-seated subcutaneous ulcer due to Candida
      species.
AB  - Deep-seated subcutaneous ulcers infected with Candida species are rare. We are
      reporting a 51-year-old Cantonese woman who had a large, deep-seated subcutaneous
      ulcer on her right shoulder for more than a year. Direct smears of the purulent
      extrusion revealed many pseudohyphae and yeast cells. Candida species were
      isolated from the purulent extrusion and further identified as Candida albicans
      and C. parapsilosis. A skin lesion biopsy contained yeast cells and pseudohyphae.
      C. parapsilosis were once isolated from the biopsy specimen. Total healing was
      obtained with itraconazole (200 mg twice daily for 16 days and then 100 mg twice
      daily for 14 days) combined with phototherapy.

PMID- 17551847
TI  - Oral yeast flora and its ITS sequence diversity among a large cohort of medical
      students in Hainan, China.
AB  - The most prevalent fungal infection of humans is candidiasis which is caused by
      species of Candida that are typical members of the commensal microbial flora of
      the oral mucosa and other body surfaces. Since species of Candida differ in
      virulence properties and susceptibilities to anti-fungal drugs, understanding the
      human commensal yeast flora will have a significant impact on designing treatment
      and prevention strategies against yeast infections. However, although there is a
      global interest in Candida species, the global distributions of Candida species
      remain largely unknown, especially among healthy hosts. Here we report the oral
      yeast flora from the surveys of over 1,000 medical students in China. Our results
      showed that this population had a yeast carriage rate (4.5%) much lower than
      other population samples reported previously from Mainland China (40-70%). In
      addition, C. albicans was isolated at a much higher frequency than those from
      other Chinese samples, with a frequency (80.9%) more similar to those in
      developed regions such as North America. The oral yeast carriage rates and yeast
      species compositions were similar between male and female students and between
      the hosts borne and raised on Hainan Island and those borne and raised on
      Mainland China. Furthermore, the sequence variation at the internal transcribed
      spacer (ITS) regions of the nuclear ribosomal RNA gene cluster was analyzed for
      strains of the dominant species, C. albicans. Our analysis identified 14 ITS
      types among the 41 Hainan isolates of C. albicans. However, only four of the 14
      ITS types were identical to those in reference strains from Europe and North
      America. Taken together, our analyses suggest that the oral yeast flora among
      host populations in China is highly heterogeneous and that there is a high ITS
      sequence diversity in the Hainan population of C. albicans.

PMID- 17551848
TI  - Identification and in vitro antifungal susceptibility testing of 200 clinical
      isolates of Candida spp. responsible for fingernail infections.
AB  - A total of 200 samples of Candida spp. that are responsible for fingernail
      infections were isolated in Belo Horizonte, MG, Brazil from April 2004 to May
      2005. The samples were identified by routine microbiological techniques and had
      the following distribution: Candida parapsilosis (40.5%), C. albicans (31.5%), C.
      tropicalis (26%), and C. guilliermondii (2%). We performed in vitro
      susceptibility tests with ciclopiroxolamine, terbinafine, ketoconazole,
      itraconazole, and fluconazole using the CLSI (Clinical and Laboratory Standards
      Institute) and EUCAST (European Committee on Antibiotic Susceptibility Testing)
      methodologies. The percentages of agreement between the two methodologies varied
      from 48 to 100% (the percentage increased to more than 60% for the majority of
      the samples). Percentages of agreement between the methodologies lower than 60%
      were seen with ketoconazole (57%) and itraconazole (48%) for samples of C.
      albicans and with fluconazole (54%) for samples of C. tropicalis. In general, we
      observed higher agreement between the values of the MICs obtained with both
      methodologies for ciclopiroxolamine and terbinafine for all tested species. With
      azoles, lower percentages of agreement between the methodologies were observed
      for samples C. albicans and C. tropicalis.

PMID- 17551849
TI  - Growth and mycotoxin production by Chaetomium globosum.
AB  - Chaetomium globosum, the most common species within this genus, produces
      chaetoglobosins A and C when cultured on building material. Relatively low levels
      of these compounds have been shown to be lethal to various tissue culture cell
      lines. This study had two major objectives: (1) to determine the frequency at
      which Chaetomium species are isolated in water-damaged buildings and (2) to
      examine the production of chaetoglobosins A and C in isolates of C. globosum
      obtained from different buildings. Out of 794 water-damaged buildings, Chaetomium
      species were isolated in 49% of these structures. C. globosum ATCC 16021 was
      grown on four different media: oatmeal agar (OA), potato dextrose agar (PDA),
      corn meal agar (CMA), and malt extract agar (MEA). After 4 weeks, fungal growth
      was evaluated based on colony diameter and the quantity of spores produced on
      agar plates. In addition, production of chaetoglobosin A and C was monitored
      using high performance liquid chromatography. Colony diameter, spore production,
      and mycotoxin production by C. globosum were the highest on OA. Out of 30 C.
      globosum isolates cultured on OA for 4 weeks, 16 produced detectable amounts of
      chaetoglobosin A and every isolate produced chaetoglobosin C.

PMID- 17551850
TI  - Validity of patient-reported health-related quality of life global ratings of
      change using structural equation modeling.
AB  - BACKGROUND: Patient-perceived global ratings of change are often used as anchors
      of health-related quality of life (HRQoL) since they are easy for clinicians to
      interpret and incorporate the patient's perception of change as a means to
      capture clinical significance. Although this approach may be preferred, the
      validity of the anchor-based approach is currently under scrutiny. OBJECTIVE: To
      estimate the explained variation in single-item domain-specific global ratings of
      change (GRCs) that is accounted for by time 1 (T1) and time 2 (T2) domain
      specific summary change scores from the Short-Form 36, V2 (SF-36) Health Survey
      in asthma primary care patients. METHODS: The baseline and first follow-up
      enrollment data to be evaluated in this investigation were part of a larger
      longitudinal HRQoL study conducted from August 2000-December 2002, in which the
      356 asthma patients from Midwestern primary care facilities completed telephone
      interviews for every two consecutive months for a year on multiple HRQoL
      measures, including the SF-36 and domain-specific GRCs. A structural equation
      modeling technique was employed to ascertain the explained variability in patient
      reported GRCs for each SF-36 domain that is accounted for by the summary change
      scores at the two time-points for four SF-36 domains (bodily pain, general health
      perception, mental health, and physical functioning). The model was estimated by
      the maximum likelihood method with the Satorra-Bentler correction for ordinal
      variables using equal threshold asymptotic covariance matrices. RESULTS:
      Multicollinearity between T1 and T2 latent constructs clouded interpretation of
      the standardized structural coefficients leading to GRCs. Correlations, however,
      revealed that all four domain-specific GRCs were more strongly related to T2-
      than T1-domain summary scores, indicating that patients were not equally relying
      on T1 and T2 to generate the GRCs. Furthermore, T1-domain summary scores were not
      of equal magnitude and opposite sign as compared to T2 scores. CONCLUSIONS: In
      this study, there is insufficient evidence to establish SF-36 domain-specific GRC
      validity in asthma primary care patients. Therefore, it is recommended to
      reassess validity before using domain-specific SF-36 GRCs to classify clinically
      important change over time.

PMID- 17551851
TI  - Somatic alterations of the NF1 gene in an NF1 individual with multiple benign
      tumours (internal and external) and malignant tumour types.
AB  - Neurofibromatosis type 1 is a common familial cancer syndrome, affecting about 1
      in every 4,000 individuals worldwide. We have carried out NF1 gene mutation
      analysis on DNA isolated from 25 tumours (dermal and plexiform neurofibromas,
      malignant peripheral nerve sheath tumour, MPNST), obtained at post-mortem from an
      NF1 patient. Macro and micro sequence alterations of the NF1 gene were studied by
      dHPLC, microsatellite, RFLP markers and multiplex ligation probe amplification
      (MLPA). The underlying germline mutation involves a deletion of exons 2 and 3. Of
      the 25 tumours studied from this patient, characterised somatic mutations were
      identified in 9 tumours, these were six small deletions (748del T, 2534-2557 del
      24bp, 2843delA, 3047-3048 del GT, 4743del G, 7720-7721 delAA), an insertion 649
      ins 73 bp, a non-sense mutation R1513X and a single splice site mutation, IVS4C-1
      G>A, eight of these represent novel sequence changes in the gene. Evidence for
      loss of heterozygosity (LOH) was identified in DNA from 7 of the tumours. Each of
      the tumours analysed contained a different somatic NF1 mutation, indicating that
      each tumour is the result of an independent somatic event. The somatic mutation
      detection rate in this study is 64% (16/25), is one of the highest rates in
      genomic DNA reported so far in a single NF1 patient. Only 68 characterised NF1
      somatic mutations have so far been reported and so our data will contribute to
      NF1 somatic mutational spectrum of the NF1 gene and will be important for
      understanding the molecular basis of NF1 tumorigenesis.

PMID- 17551852
TI  - Building research capacity through partnerships: Spinal Cord Injury-Vocational
      Integration Program Implementations and Outcomes inaugural meeting.

PMID- 17551853
TI  - Directed rehabilitation reduces pain and depression while increasing independence
      and satisfaction with life for patients with paraplegia due to epidural
      metastatic spinal cord compression.
AB  - We determined whether directed rehabilitation affected survival, pain,
      depression, independence, and satisfaction with life for veterans who were
      nonambulatory after spinal epidural metastasis (SEM) treatment. We compared 12
      consecutive paraplegic veterans who received 2 weeks of directed rehabilitation
      with a historical control group of 30 paraplegic veterans who did not receive
      rehabilitation. The rehabilitation program emphasized transfers, bowel and
      bladder care, incentive spirometry, nutrition, and skin care. The outcome
      measures were survival, independence, pain levels, depression, and satisfaction
      with life. Patients receiving rehabilitation had longer median survivals, fewer
      deaths from myelopathic complications, less pain 2 weeks after SEM treatment,
      lower depression scores, and higher satisfaction with life scores. In addition,
      among the patients who received rehabilitation, eight became independent for
      transfers (vs zero controls) and nine returned home (vs six controls). We
      conclude that directed rehabilitation reduced patients' pain levels and increased
      their mobility, survival, and life satisfaction.

PMID- 17551854
TI  - Effect of ankle-foot orthosis on roll-over shape in adults with hemiplegia.
AB  - Ankle-foot orthoses (AFOs) are intended to improve toe clearance during swing and
      ankle position at initial contact (IC) and midstance. Changes that lead to
      improved ankle-foot kinematics may result in a more biomimetic roll-over shape
      (ROS). ROS is the effective geometry to which the ankle-foot complex conforms
      between IC and contralateral IC. An effective ROS during gait may facilitate
      forward progression. This study investigated the effect of an AFO on ROS in
      adults with hemiplegia following stroke. Kinematic and force data were recorded
      from 13 people with hemiplegia and 12 controls. Hemiplegic subjects walked at a
      self-selected speed with and without an articulated AFO with plantar flexion
      stop. For the involved limb, the AFO significantly increased the ROS arc length
      (from 32.6% to 55.7% of foot length [FL]) and arc radius (67.4% to 139.3% of FL)
      and significantly altered the sagittal plane location of the first center of
      pressure (COP) point, moving it posterior to the ankle center (-1.2% to -20% of
      FL) (p < 0.002 for all comparisons). However, when hemiplegic patients walked
      with an AFO, their mean arc radius was greater, mean arc length less, and the
      first COP point further posterior than those of control subjects.

PMID- 17551855
TI  - Randomized clinical trial: group counseling based on tinnitus retraining therapy.
AB  - The main component of tinnitus retraining therapy (TRT) is structured counseling.
      We conducted a randomized clinical trial to test the hypothesis that group
      educational counseling based on TRT principles would effectively treat veterans
      who have clinically significant tinnitus. Veterans with clinically significant
      tinnitus were randomized into one of three groups: educational counseling,
      traditional support, and no treatment. Subjects in the first two groups attended
      four 1.5 h group sessions each week. All subjects completed outcome
      questionnaires at baseline and at 1, 6, and 12 mo. A total of 269 subjects
      participated: 94 in the educational counseling group, 84 in the traditional
      support group, and 91 in the no-treatment group. Statistical analyses showed that
      educational counseling provided significantly more benefit than either
      traditional support or no treatment, as measured by the Tinnitus Severity Index.
      Results suggest that group educational counseling can significantly benefit many
      tinnitus patients and could be integral to a "progressive intervention" approach
      to tinnitus clinical management.

PMID- 17551856
TI  - Chair rise strategies in older adults with functional limitations.
AB  - Studies investigating chair rise (CR) strategies in older adults, including the
      identification of CR strategies in the clinical setting, are limited. We
      identified biomechanical differences between CR strategies performed by older
      adults. The "healthy" momentum transfer (MT), the exaggerated trunk flexion
      (ETF), and the dominant vertical rise (DVR) CR strategies were observed in 29
      women and 17 men (64-88 yr) with functional limitations. The DVR strategy
      required the greatest knee torque (mean = 12.76 moment-% body weight). Maximum
      knee torque occurred significantly earlier for the ETF strategy (mean = 47% CR
      time). Lift-off time was earliest for the ETF strategy (mean = 32% CR time). Peak
      trunk flexion was the primary distinguishing biomechanical measure for
      classifying CR strategy. This finding may offer clinicians an easy method of
      identifying CR strategies during evaluation. Because of DVR and ETF movement
      timing and torque demands, we conclude that MT is the safest and most preferable
      CR strategy.

PMID- 17551858
TI  - Outcomes in spinal cord injury.

PMID- 17551857
TI  - Dynamic biomechanical model for assessing and monitoring robot-assisted upper
      limb therapy.
AB  - This article describes the design, validation, and application of a dynamic
      biomechanical model that assesses and monitors trajectory, position, orientation,
      force, and torque generated by upper-limb (UL) movement during robot-assisted
      therapy. The model consists of two links that represent the upper arm and
      forearm, with 5 degrees of freedom (DOF) for the shoulder and elbow joints. The
      model is a useful tool for enhancing the functionality of poststroke robot
      assisted UL therapy. The individualized inertial segment parameters were based on
      anthropometric measurements. The model performed inverse dynamic analysis of UL
      movements to calculate reaction forces and moments acting about the 3-DOF
      shoulder and 2-DOF elbow joints. Real-time fused biofeedback of a 6-DOF force
      sensor and three-dimensional (3-D) pose sensors supported the model validation
      and application. The force sensor was mounted between the robot manipulator and
      the subject's wrist, while the 3-D pose sensors were fixed at specific positions
      on the subject's UL segments. The model input and output parameters were stored
      in the subject's database, which is part of the rehabilitation information
      system. We assigned 20 nondisabled subjects three different therapy exercises to
      test and validate the biomechanical model. We found that when the biomechanical
      model is taught an exercise, it can accurately predict a subject's actual UL
      joint angles and torques and confirm that the exercise is isolating the desired
      movement.

PMID- 17551859
TI  - Spinal Cord Independence Measure: comprehensive ability rating scale for the
      spinal cord lesion patient.
AB  - The Spinal Cord Independence Measure (SCIM) is, at present, the only
      comprehensive rating scale that measures the ability of patients with spinal cord
      lesions (SCL) to perform everyday tasks according to their value for the patient.
      This article describes the scale and its scoring techniques, presents the
      purposes for which SCIM is used, and details its advantages for patients with
      SCL. Findings of an international multicenter study supported the validity and
      reliability of its third version, despite intercultural differences, and
      demonstrated its superior sensitivity to changes in function compared with the
      Functional Independence Measure. SCIM can be used in patients with SCL for
      ability assessment, as a compact guide for determining certain treatment goals,
      and for outcome assessment following interventions designed to promote recovery.

PMID- 17551860
TI  - Review of physiological motor outcome measures in spinal cord injury using
      transcranial magnetic stimulation and spinal reflexes.
AB  - This article reviews methods that have been developed as part of a clinical
      initiative on improving outcome measures for motor function assessment in
      subjects with spinal cord injury (SCI). Physiological motor outcome measures
      originally developed for limbs-transcranial magnetic stimulation (TMS) of the
      motor cortex to elicit motor-evoked potentials (MEPs) and mechanical stimulation
      to elicit spinal reflexes-have been extended to muscles of the trunk. The impetus
      for this development is the lack of a motor component in the American Spinal
      Injury Association clinical assessment for the thoracic myotomes. The application
      of TMS to the assessment of limb muscles is reviewed, followed by consideration
      of its application to the assessment of paravertebral and intercostal muscles.
      Spinal reflex testing of paravertebral muscles is also described. The principal
      markers for the thoracic SCI motor level that have emerged from this clinical
      initiative are (1) the threshold of MEPs in paravertebral muscles in response to
      TMS of the motor cortex, (2) the facilitation pattern and latency of MEPs in
      intercostal muscles during voluntary expiratory effort, and (3) the absence of
      long-latency reflex responses and the exaggeration of short-latency reflex
      responses in paravertebral muscles.

PMID- 17551861
TI  - Quantitative sensory tests (perceptual thresholds) in patients with spinal cord
      injury.
AB  - This article was presented at the Premeeting Workshop on Outcome Measures at the
      American Spinal Injury Association (ASIA) Annual Scientific Meeting in Dallas,
      Texas, in May 2005. The article summarizes preliminary findings of three
      quantitative sensory tests that were evaluated as part of the International
      Spinal Research Trust Clinical Initiative study: perceptual thresholds to
      electrical, vibration, and thermal stimulation. The results gathered so far
      suggest that the three tests are simple, reproducible, and applicable in a
      clinical setting. The tests seem to add resolution and sensitivity to the
      standard clinical testing and could be useful adjuncts in longitudinal monitoring
      of spinal cord injury for research purposes.

PMID- 17551862
TI  - Development of international standards to document sexual and reproductive
      functions after spinal cord injury: preliminary report.
AB  - Clinicians need standard terminology to communicate effectively about remaining
      autonomic function in persons after spinal cord injury. This article illustrates
      the development of standard nomenclature that describes the impact of injury on
      sexual functioning. A standard anatomic diagnosis and a secondary means of
      describing the presence of male and female sexual dysfunction, genital arousal,
      and orgasmic function are discussed.

PMID- 17551863
TI  - Assessment of upper limb in tetraplegia: considerations in evaluation and
      outcomes research.
AB  - This article briefly discusses several measurement tools for evaluating the upper
      limb of persons with tetraplegia. Muscle strength testing and electrodiagnostics
      are discussed as they relate to technique and usefulness for clinical trials.
      Standardized measures of hand function are reviewed; their limitations for
      clinical trials during acute spinal cord injury (SCI) care are acknowledged and
      their strengths for interventional studies and clinical trials during chronic
      phases of SCI care are defined. Recommendations are set forth for incorporating
      the International Classification for Surgery of the Hand in Tetraplegia motor and
      sensory examinations as adjuncts to the International Standards for Neurological
      Classification of SCI motor and sensory examinations and for further developing
      electrodiagnostic techniques as measurement tools for acute clinical trials. The
      Grasp and Release Test is described and recommended for clinical trials involving
      persons in the chronic stages of SCI. Lastly, we note that much work remains in
      the development, validation, and clinical deployment of an assessment of upper
      limb function in SCI.

PMID- 17551864
TI  - Assessment of autonomic dysfunction following spinal cord injury: rationale for
      additions to International Standards for Neurological Assessment.
AB  - We present a preliminary report of the discussion of the joint committee of the
      American Spinal Injury Association (ASIA) and the International Spinal Cord
      Society concerning the development of assessment criteria for general autonomic
      function testing following spinal cord injury (SCI). Elements of this report were
      presented at the 2005 annual meeting of the ASIA. To improve the evaluation of
      neurological function in individuals with SCI and therefore better assess the
      effects of therapeutic interventions in the future, we are proposing a
      comprehensive set of definitions of general autonomic nervous system dysfunction
      following SCI that should be assessed by clinicians. Presently the committee
      recommends the recognition and assessment of the following conditions: neurogenic
      shock, cardiac dysrhythmias, orthostatic hypotension, autonomic dysreflexia,
      temperature dysregulation, and hyperhidrosis.

PMID- 17551865
TI  - Domains of outcomes in spinal cord injury for clinical trials to improve
      neurological function.
AB  - Selecting appropriate outcome measures in spinal cord injury clinical trials that
      aim to improve spinal cord function is a challenging task. Proving that an
      intervention has the intended effect on neurological functioning is insufficient.
      Any improvement must be shown to be clinically significant-that is, makes a
      change in the life of the person. Rehabilitation, which seeks to maximize
      function despite residual impairments, complicates this task. Small improvements
      in function due to a spinal cord intervention may be masked by improvements in
      function due to rehabilitation, particularly in the initial rehabilitation phase
      of care. Understanding outcome domains in models of disablement will facilitate
      selection or development of assessment tools appropriate for the trial in
      question. This article describes an expanded World Health Organization model of
      functioning that defines the domains of Impairment, Capability/Functional
      Limitation, and Activity, as well as the subdomains of Capacity and Performance,
      and gives examples of measurement instruments in use or under development in each
      domain.

PMID- 17551866
TI  - Dynamometry testing in spinal cord injury.
AB  - Persons with a spinal cord injury (SCI) demonstrate strength deficits that can
      limit their functional ability to perform activities of daily living. For a
      specific lesion level, performance of functional activities is related to the
      level of muscle strength. Consequently, in clinical practice, we need reliable
      measures of muscle strength to determine mobility and self-care ability. Muscle
      strength testing is used to document recovery or loss of motor function early in
      SCI, as well as measure improvements in strength in chronic SCI. We also need
      such measures for research purposes to determine the efficacy of clinical trials.
      Several methods are available for testing muscle strength of persons with SCI,
      such as handheld, handgrip, and isokinetic dynamometers. This article provides an
      overview of muscle-contraction definitions and testing methodologies and
      discusses the reliability of these testing methods and dynamometry devices.

PMID- 17551867
TI  - Research on pain and pain management in Veterans Health Administration: promoting
      improved pain care for veterans through science and scholarship.

PMID- 17551868
TI  - Veterans Health Administration's pain research portfolio and publications.

PMID- 17551869
TI  - Effects of depression and pain severity on satisfaction in medical outpatients:
      analysis of the Medical Outcomes Study.
AB  - Patient satisfaction has been used as a healthcare quality indicator. We examined
      how depression and pain severity affected satisfaction in medical outpatients.
      Data from the Medical Outcomes Study were analyzed. The primary outcomes were
      seven satisfaction domains from the Patient Satisfaction Questionnaire.
      Depression was identified through a clinical interview, and pain was assessed
      with the 36-item Short Form Bodily Pain scale. We performed multivariate linear
      regression to predict satisfaction in outpatients with depression and pain. Minor
      and major depression were present in 23.4% and 15.0% of the sample, respectively.
      Pain was present in more than half the patients (50.6%). Both minor and major
      depression as well as pain severity were strongly associated with lower
      satisfaction scores. Increased age and diagnosis of heart failure predicted
      higher satisfaction scores. Depression and pain have a substantial effect on
      patient satisfaction. Future studies should assess the reasons for
      dissatisfaction with care in patients with depression and pain.

PMID- 17551870
TI  - Veterans seeking treatment for posttraumatic stress disorder: what about comorbid
      chronic pain?
AB  - Our primary aim was to document the rate of comorbidity of physician-diagnosed
      chronic pain conditions in veterans who were seeking treatment for posttraumatic
      stress disorder (PTSD). Chronic pain diagnoses (e.g., chronic low-back pain and
      osteoarthritis) were examined with retrospective chart review. Of the patients
      with PTSD, 66% had chronic pain diagnoses at pretreatment. These findings are
      consistent with previous studies that documented the high comorbidity of chronic
      pain and PTSD using samples of pain patients. Our secondary aim was to examine
      pain ratings before, during, and after PTSD treatment. Using data that were a
      part of clinical practice, we found that patients with more pain before treatment
      reported reductions in pain over the course of PTSD treatment and in the 4 months
      following treatment. While our results must be interpreted cautiously because of
      multiple confounding factors and the absence of experimental manipulation, they
      highlight the importance of PTSD and pain comorbidity.

PMID- 17551871
TI  - Prevalence and correlates of posttraumatic stress disorder and chronic severe
      pain in psychiatric outpatients.
AB  - This cross-sectional study reports the prevalence and correlates of posttraumatic
      stress disorder (PTSD) and chronic severe pain in psychiatric outpatients (n =
      295), a sample that has not previously been examined for the co-occurrence of
      these two disorders. Nearly half the participants (46%) met the Diagnostic and
      Statistical Manual of Mental Disorders-Fourth Edition criteria for PTSD; 40%
      reported chronic severe pain; and 24% had both disorders. We compared four groups
      of subjects who had either both disorders, PTSD only, chronic severe pain only,
      or neither disorder for variables previously found to be associated with both
      disorders or either disorder alone (e.g., psychiatric distress, substance use,
      stressful life events, physical/sexual abuse). Multiple pairwise comparisons
      indicated that persons with both disorders were significantly different from
      persons with neither disorder for all dependent variables and that they had
      greater physical and psychosocial stressors. Persons with either PTSD or chronic
      severe pain alone were more likely to have a chronic medical condition, higher
      ratings of psychiatric distress, and more stressful life events than persons with
      neither disorder. Mental health treatment providers should be aware of the
      potential for the co-occurrence of PTSD and chronic severe pain and of the many
      related factors in psychiatric outpatients.

PMID- 17551872
TI  - Pain and combat injuries in soldiers returning from Operations Enduring Freedom
      and Iraqi Freedom: implications for research and practice.
AB  - Operation Enduring Freedom (OEF) and Operation Iraqi Freedom (OIF) have resulted
      in a growing number of seriously injured soldiers who are evacuated to the United
      States for comprehensive medical care. Trauma-related pain is an almost universal
      problem among these war-injured soldiers, and several military and Department of
      Veterans Affairs initiatives have been implemented to enhance pain care across
      the continuum of medical services. This article describes several innovative
      approaches for improving the pain care provided to OEF and OIF military personnel
      during acute stabilization, transport, medical-surgical treatment, and
      rehabilitation and presents summary data characterizing the soldiers, pain
      management services provided, and associated outcomes. We also identify some of
      the pain assessment, classification, and treatment challenges emerging from work
      with this population and provide recommendations for future research and practice
      priorities.

PMID- 17551873
TI  - Efficacy of selected complementary and alternative medicine interventions for
      chronic pain.
AB  - Complementary and alternative medicine (CAM) is a group of diverse medical and
      healthcare systems, therapies, and products that are not presently considered
      part of conventional medicine. This article provides an up-to-date review of the
      efficacy of selected CAM modalities in the management of chronic pain. Findings
      are presented according to the classification system developed by the National
      Institutes of Health National Center for Complementary and Alternative Medicine
      (formerly Office of Alternative Medicine) and are grouped into four domains:
      biologically based medicine, energy medicine, manipulative and body-based
      medicine, and mind-body medicine. Homeopathy and acupuncture are discussed
      separately as "whole or professionalized CAM practices." Based on the guidelines
      of the Clinical Psychology Division of the American Psychological Association,
      findings indicate that some CAM modalities have a solid track record of efficacy,
      whereas others are promising but require additional research. The article
      concludes with recommendations to pain practitioners.

PMID- 17551874
TI  - Preliminary evaluation of reliability and criterion validity of Actiwatch-Score.
AB  - The restoration of normal physical activity is a primary objective of most
      chronic pain rehabilitative interventions, yet few clinically practical objective
      measures of activation exist. Actigraphy is one technology that promises to fill
      this void in the field of pain outcomes assessment. This study evaluates the
      measurement properties of one of several commercially available actigraphs: the
      Actiwatch-Score (AW-S). We conducted separate trials to examine concordance
      between units when worn concurrently at the same and different body sites and to
      compare the AW-S to a validated optical three-dimensional motion-tracking system.
      The data indicate that the AW-S has excellent interunit reliability and good
      criterion validity, but its intersite reliability varies with activity type.
      These results suggest that this device, and those like it, warrants further
      investigation and is likely to yield valuable data regarding the optimal
      application of this technology.

PMID- 17551875
TI  - A closer look at pain and hepatitis C: preliminary data from a veteran
      population.
AB  - An association between the hepatitis C virus (HCV) and various pain diagnoses,
      including arthritis, fibromyalgia, and peripheral neuropathy, has been reported.
      In this article, we review the literature on the relationship between HCV and
      pain, highlighting current knowledge as well as methodological issues that exist
      in many studies. We also present preliminary findings from a survey conducted at
      two Department of Veterans Affairs facilities to assess the scope and impact of
      pain on functioning in veterans with HCV. Our results indicate that pain is very
      prevalent within this population and that HCV-positive veterans who experience
      persistent pain have significant depressive symptoms and engage in high-risk
      behaviors, such as cigarette smoking and alcohol use. Finally, we draw upon our
      review and preliminary results to propose areas of future rehabilitative research
      and to address the implications for clinicians working with patients with
      comorbid HCV and pain.

PMID- 17551876
TI  - Overview of the relationship between pain and obesity: What do we know? Where do
      we go next?
AB  - Overweight/obesity and pain are significant problems of increasing prevalence;
      understanding the relationship between the two is the focus of a growing body of
      research. Findings from this review support a likely relationship between
      increasing weight and pain conditions such as osteoarthritis and low back pain.
      Longitudinal studies suggest overweight/obesity early in life is a risk factor
      for pain, and the co-occurrence of pain and overweight/obesity negatively affects
      quality of life. The mechanism of relationship is unknown but is hypothesized to
      include mechanical and metabolic abnormalities, possibly secondary to lifestyle
      choices. Observations from a few studies demonstrate that treatments for obesity
      reduce pain secondary to weight loss. Few studies examine both pain and weight as
      primary outcomes, and variability in measurement makes comparisons and
      conclusions difficult. Research should focus on expanding knowledge about
      mechanisms of the relationship between pain and obesity, testing explanatory
      models addressing their co-occurrence, and developing treatments that most
      effectively target this comorbidity.

PMID- 17551877
TI  - Medical residents' beliefs and concerns about using opioids to treat chronic
      cancer and noncancer pain: a pilot study.
AB  - This study assessed and compared residents' beliefs and concerns about using
      opioids for treating pain in patients with cancer and noncancer low back pain
      (NLBP). Participants included 72 Internal Medicine and Medicine-Pediatrics
      residents who completed a survey questionnaire. Based on a scale of 0 = "No
      concern" to 10 = "Very concerned," residents expressed greater concern that
      treating NLBP with opioids, compared with cancer-related pain, causes addiction
      (6.01 vs 1.15), abuse (5.57 vs 1.39), and side effects (4.76 vs 2.87); limits
      other treatments (5.36 vs 1.30); draws criticism from faculty (4.33 vs 0.88); or
      risks sanctioning (state board 4.12 vs 1.12, legal 4.06 vs 1.17); p < 0.001 for
      each (paired t-tests). They had more comfort (8.94 vs 4.31) and more empathy
      (9.09 vs 6.79) using opioids to treat for cancer pain than NLBP and would give
      whatever doses necessary for pain control (8.41 vs 3.66); p < 0.001 for each. Our
      findings show that residents are far more concerned about using opioids to treat
      NLBP than cancer-related pain.

PMID- 17551878
TI  - Persistent benefits of rehabilitation on pain and life quality for nonambulatory
      patients with spinal epidural metastasis.
AB  - We determined whether the benefits of directed rehabilitation for pain,
      depression, and satisfaction with life persisted for veterans who were
      nonambulatory after spinal epidural metastasis (SEM) treatment. Twelve
      consecutive veterans (paraplegic after SEM treatment) who received 2 weeks of
      directed rehabilitation were compared with a historical control group of thirty
      paraplegic veterans who did not receive rehabilitation. Subjects were followed
      until death. Pain levels, depression, satisfaction with life, and consumption of
      pain medication were measured. Subjects who received rehabilitation had less
      pain, consumed less pain medication, were less depressed, and had higher
      satisfaction with life. The benefits to the rehabilitated subjects persisted
      until their deaths. We conclude that spinal cord injury rehabilitation for
      nonambulatory subjects with SEM produces persistent benefits for pain,
      depression, and satisfaction with life.

PMID- 17551879
TI  - Pain and palliative medicine.
AB  - Severe pain is highly prevalent, with rates of 40% to 70% in patients with
      advanced cancer, liver disease, heart failure, human immunodeficiency virus, and
      renal failure. Wide variations in pain assessment and reporting methods and the
      measurement of multiple symptoms should be addressed in future studies. Regarding
      psychological approaches, determining whether hypnotherapy or other individual
      psychotherapeutic interventions reduce pain and/or psychological distress in a
      palliative care population is difficult. Interest is increasing in the concept of
      demoralization syndromes and the role of posttraumatic stress disorder in
      modulating responses to pain at the end of life. We review evidence from multiple
      studies that the use of rehabilitative therapy improves functional status and
      pain control among patients with advanced cancer, and we raise the possibility
      that rehabilitation therapy will be helpful in patients with other advanced
      diseases. We summarize ongoing clinical trials of electronic order sets, clinical
      care pathways, and care management pathways to improve pain management in
      palliative care. Wagner's Chronic Illness Model provides a way of analyzing how
      healthcare systems can be changed to provide adequate and continuing pain
      management in palliative care. Much work remains to ensure that pain is
      recognized, treated, and monitored effectively.

PMID- 17551880
TI  - Moving to new settings: pilot study of families' perceptions of professional
      caregivers' pain management in persons with dementia.
AB  - Persons with advanced dementia often have pain that is underrecognized and
      undertreated primarily because they cannot clearly communicate their needs.
      Consequently, they receive fewer analgesics than cognitively intact persons with
      the same conditions. Several assessment methods have been developed in the past
      decade, yet pain assessment and management problems persist in all care settings.
      These problems are likely to persist when patients move between levels of care.
      In this study, we determined from family caregivers whether pain was problematic
      when their family members with dementia moved to different care settings (e.g.,
      admission or transfer). A total of 34 family caregivers responded to an anonymous
      survey; 50% reported that pain was not discussed at admission or after entry into
      a new care setting, and 67% were not confident that staff could detect pain.
      Respondents' recommendations for improving pain management included regular
      observation and assessment, timely and consistent pain medication administration,
      communication with family caregivers, and staff education.

PMID- 17551881
TI  - Determining mild, moderate, and severe pain equivalency across pain-intensity
      tools in nursing home residents.
AB  - Older adults in nursing homes experience pain that is often underassessed and
      undertreated. Visual analog pain-intensity scales, recommended for widespread use
      in adults, do not work well in the older adult population. A variety of other
      tools are in use, including the Verbal Descriptor Scale, the Faces Pain Scale
      (FPS), and the Numeric Rating Scale. These tools are more acceptable to older
      adults, but no agreement exists about how to compare the resulting pain-intensity
      scores across residents. This study examined the equivalency of pain-intensity
      scores for 135 nursing home residents who reported their pain on the three
      different instruments. The results were validated with a second sample of 135
      nursing home residents. The pain levels across the three tools were highly
      correlated, but residents were found to underrate higher pain intensity on the
      FPS. A modification of scoring for the FPS led to greater agreement across the
      three tools. The findings have implications for use of these tools for quality
      improvement and public reporting of pain.

PMID- 17551882
TI  - Cognitive impairment and pain management: review of issues and challenges.
AB  - The assessment and treatment of pain in persons with cognitive impairments pose
      unique challenges. Disorders affecting cognition include neurodegenerative,
      vascular, toxic, anoxic, and infectious processes. Persons with memory, language,
      and speech deficits and consciousness alterations are often unable to communicate
      clearly about their pain and discomfort. Past research has documented that
      persons with cognitive impairments, particularly dementia, are less likely to ask
      for and receive analgesics. This article provides an overview of the assessment,
      treatment, and management of pain in adults with cognitive impairments. We review
      types of cognitive impairment; recent work specific to best practices for pain
      management in patients with dementia, including assessment-tool development and
      pharmacological treatment; challenges in patients with delirium and in medical
      intensive care and palliative care settings; and directions for future research.

PMID- 17551883
TI  - [Daytime ventilatory efficiency in obstructive sleep apnea syndrome--influence of
      CPAP-therapy].
AB  - BACKGROUND: Obstructive sleep apnea syndrome (OSAS) is a nocturnal breathing
      disorder with possibly negative consequences on daytime control of ventilatory
      drive. We therefore investigated ventilatory efficiency, defined as the
      ventilatory equivalent for CO2 (VaE/VaCO2), in patients with OSAS during exercise
      before and under treatment with continuous positive airway pressure (CPAP).
      PATIENTS AND METHODS: In 21 patients with untreated OSAS, ventilatory efficiency,
      described as the slope (DeltaVaE vs. VaCO2) and the lowest ratio (VaE/VaCO2 min)
      of the ventilatory equivalent for CO2, was determined below the anaerobic
      threshold using spiroergometry. A follow-up after at least 6 months of CPAP
      therapy was performed in 16 of these patients and in 5 CPAP-neglecting patients
      with OSAS, who served as controls. RESULTS: In 21 patients with untreated OSAS,
      DeltaVaE vs. VaCO2 was significantly and VaE/VaCO2 min non-significantly lower,
      revealing better ventilatory efficiency, compared to normal values. In 16
      patients, ventilatory efficiency did not change after on average 305.7 +/- 104.8
      nights of CPAP-therapy, compared to 5 controls. CONCLUSIONS: OSAS is not
      associated with a disturbed ventilatory efficiency during exercise. Long-term
      CPAP-therapy does not change ventilatory efficiency during exercise in patients
      with OSAS. The improved ventilatory efficiency during exercise compared to normal
      controls may be due to differences concerning anthropometric data (e. g.,
      obesity, hypertension) and cardiopulmonary exercise-test (45 degrees lying
      position).

PMID- 17551884
TI  - [A German military cemetery in Switzerland].

PMID- 17551885
TI  - [Diabetes study in Bavaria: known risk factors correlate with an increased level
      of HbA1c].
AB  - BACKGROUND AND OBJECTIVE: Approximately six million Germans have been diagnosed
      with diabetes mellitus. A continuously increasing number of people with diabetes
      is expected within the next few years. Genetic disposition, age and especially
      lifestyle play an important role in the development of the disease. Diabetes
      normally develops during a long preclinical phase. During this preclinical phase
      an impaired glucose tolerance can easily be detected. Since an impaired glucose
      tolerance is often reversible the onset of diabetes can be prevented effectively
      by a change of lifestyle during this phase. The Bavarian Red Cross Blood
      Transfusion Service therefore determined the diabetes risk among its blood donors
      during two one-week study periods. PATIENTS AND METHODS: The diabetes risk of the
      participating donors was assessed by using the FindRisk diabetes test published
      by the German Diabetes Foundation and the HbA1c test. RESULTS: Approximately 12
      percent of the participants (8187 persons aged 18-68 years) showed a moderate,
      high or even very high risk of developing diabetes within the next 10 years. The
      probability of developing the disease ranged from 17% (moderate risk) to 50%
      (very high risk). This corresponds to 3% of persons with unknown diabetes among
      the total population. An elevated HbA1c was found in approximately 5% of the
      donors in the first study week and in approximately 19% in the second study week.
      The analysis of the questionnaire and the HbA1c results indicated that elevated
      HbA1c values correlate with known diabetes risk factors. Persons with a body mass
      index greater than 25, an increased score in the FindRisk questionnaire and aged
      over 50 years more frequently showed an elevated HbA1c value. CONCLUSIONS: The
      combination of a diabetes risk questionnaire and HbA1c testing could be used
      successfully for diabetes screening in an identified risk group.

PMID- 17551886
TI  - [Septic shock with purpura fulminans after a dog bite].
AB  - HISTORY AND CLINICAL FINDINGS: A 61-year-old man presented with a four-day
      history of back pain and nonspecific abdominal pain. His condition had
      significantly worsened since the day before admission with generalized weakness
      and dyspnea. His temperature was 39.1 C, he had tachycardia and was tachypneic.
      Peripheral cyanosis was noted. The abdomen was soft with mild epigastric
      tenderness. A diffuse skin rash developed with increasing petechial bleeding and
      central necrosis. It was revealed that he had been bitten by a dog several weeks
      before admission. INVESTIGATIONS: Laboratory data indicated an acute inflammatory
      process with a marked increase in white blood cells and C-reactive protein. An
      elevated procalcitonin level suggested a systemic bacterial infection. Chest X
      ray and abdominal CT scan were unremarkable. Echocardiography revealed a globally
      hypokinetic heart with no evidence of valvular vegetations. One set of blood
      cultures grew micro-aerophilic, Gram-negative rods. Gene sequencing identified
      the slow growing, fastidious bacillus as CAPNOCYTOPHAGA CANIMORSUS. TREATMENT AND
      COURSE: The patient was admitted to the intensive care unit and initially treated
      with intravenous piperacillin/tazobactam and hydrocortisone for septic shock.
      Transfusions of platelets and blood products were given because of disseminated
      intravascular coagulation. The patient developed multi-organ failure requiring
      ventilation and hemodialysis; he died four days after admission. CONCLUSIONS: As
      a rare cause of septicemia, especially in immunocompromised patients,
      Capnocytophaga canimorsus infection should be considered after an animal bite.
      Given the slow growth of this bacterium in culture, Gram-staining of a peripheral
      blood smear may provide an early diagnosis and avoid delay before appropriate
      antibiotic therapy, which may favorably influence the potentially fatal course,
      is started.

PMID- 17551887
TI  - [Coronary aneurysm of the ramus interventricularis anterior and right coronary
      artery and significant stenosis in both vessels (coronary two-vessel disease].

PMID- 17551888
TI  - [Temporal arteritis].

PMID- 17551889
TI  - [Epidemiology of listeriosis in Germany: a changing but ignored pattern].
AB  - Listeriosis is emerging as a food-borne disease. Although the incidence of
      clinical presentations is low, this infectious disease with a rather poor
      prognosis deserves attention. Approximately 20-30% of patients with recognized
      listeriosis die in spite of an appropriate antibiotic regimen. In the last two
      years the number of registered cases of listeriosis in Germany has more than
      doubled. This increase is clearly due exclusively to the rising number of
      infections in elderly persons, while the number of infections in newborns has
      remained constant. Genotyping does not show a conclusive correlation between
      human and food isolates. Since the human isolates belong to numerous different
      clones. There is no specific food or group of food items that can be held
      responsible for the infections. This view is also supported by the fact that
      listeriosis cases occur sporadically and not in outbreaks, making it highly
      unlikely that industrially produced and widely distributed food items are the
      cause. Furthermore, even within the food isolates there is a large diversity of
      clones. A comprehensive explanation for the changes in the epidemiology of human
      listeriosis has yet to be given.

PMID- 17551890
TI  - A pilot study of a case management program for patients with chronic obstructive
      pulmonary disease (COPD).
AB  - The purpose of this study was to develop a case management program for patients
      with chronic obstructive pulmonary disease (COPD) and to test the effects of the
      developed program on patient length of stay in the hospital, medical costs,
      disease knowledge and level of satisfaction with nursing care received. This
      quasi-experimental study focused on a group of 50 COPD patients (24 in the
      control group and 26 in the experimental one), all treated in one hospital
      medical ward in northern Taiwan. The control group received routine care, while
      those in the experimental group received a COPD case management protocol. Data
      for the control group was collected between September of 2003 and January 2004.
      Data for the experimental group was collected between April and December 2004.
      Data collection instruments included medical records, the COPD Knowledge
      Measurement scale, and the Patient Satisfaction with Nursing Care Questionnaire.
      Descriptive and inferential statistical analyses were applied to describe
      demographics, length of stay, medical cost, patient disease-related knowledge,
      and patient satisfaction with nursing care. Results indicated that, while the
      study found no significant difference in length of stay and medical cost between
      the two groups, the use of case management procedures improved patient disease
      related knowledge and satisfaction with nursing care. This conclusion supports
      the premise that case management improves patient care in these two dimensions
      and is, thus, an effective approach in the management of patients diagnosed with
      secondary COPD infections.

PMID- 17551891
TI  - Reliability and validity of a chinese version of the pediatric asthma symptoms
      scale.
AB  - As a construct, asthmatic severity provides a framework to understand the
      different reaction in children to their condition. Assessing asthmatic severity
      is a challenging task for most researchers and clinicians due to a lack of valid
      instruments to measure the severity of asthma of children in home settings. The
      purpose of this study was to examine the psychometric properties of a Chinese
      version of the Pediatric Asthma Symptoms Scale (C-PASS) as applied to an ethnic
      Chinese population in Taiwan. Firstly, five pediatric nurses holding masters'
      degrees assessed consistency between Chinese and English versions of the
      Pediatric Asthma Symptoms Scale. Secondly, internal consistent reliability, split
      half reliability, content validity, criterion-related validity, and construct
      validity were established. An 8-item C-PASS was completed by mothers of 70
      children (65.7% boys) of ages 8.35 years. Both the internal consistency and
      Guttman split-half reliability were .87. The content validity index (CVI) was
      over .80. The correlation coefficient between C-PASS and concurrent measures of
      the rating of lost control of life by mothers was .273 (p = .022). The criterion
      related validity was supported for C-PASS. Factor analysis indicated that a scale
      of two dimensions accounted for 67.92% of the variance. A high inter-correlation
      was further identified between these two dimensions. Results showed C-PASS to be
      a reliable and valid instrument when used on Taiwanese children with asthma. It
      can serve as a valuable assessment tool in clinical practice to identify
      asthmatic severity levels for which intervention is advised.

PMID- 17551892
TI  - A journey of restoring self-confidence: the life experiences of women recipients
      of augmentation mammaplasty.
AB  - The purpose of this qualitative research study was to explore the preoperative
      through postoperative phase experience of women who had undergone augmentation
      mammaplasty. Nine women undergoing augmentation mammaplasty were selected by
      purposive sampling and interviewed using semi- structured, open-ended interview
      guidelines. Researchers used Symbolic interactionism to frame their overall
      perspective and analyzed data with the content analysis method. Rigors of data
      analysis were adopted credibility, transferability, dependability and
      confirmability proposed by Guba and Lincoln. The main theme of living experience
      of women who received augmentation mammaplasty could be summarized as "a journey
      to restore self-confidence". The categories identified within this journey
      included: (1) the invisible standards of breast beauty; (2) Taking courageous
      action to make changes; (3) conflicts between the natural and artificial. The
      above findings provided initial qualitative data from Taiwanese women's
      perspective. By better understanding their experience, nurses can become
      increasingly sensitive to patients' psychosocial adjustment and provide
      prudential nursing care.

PMID- 17551893
TI  - An oral historical study of the development of the discipline of military nursing
      in Taiwan from 1948 to 1970.
AB  - In an attempt to redress the gap in Chinese nursing and military history, this
      study aims to provide an understanding of the nature of military nursing
      development from 1948 to 1970. The National Defense Medical Center (NDMC) was
      established in 1902 and is recognized as the first military medical school in
      Chinese history. In 1949, in order to continue her studies, Prof. Fu-I Chao
      followed the school, when it moved from mainland China to Taiwan. The school's
      move was a result of the defeat on mainland China of the nationalist government
      led by Generalissimo Chiang Kai-Shek. The researchers adopted an oral history
      approach. This consisted of a literature review, the collection of photographs, a
      review of formal documents and four face-to-face in-depth interviews with Prof.
      Chao. After data collection, content analysis was performed on the information
      collected. The study explored the development of the discipline of military
      nursing in its historical, social, and economic context. Four themes emerged.
      These were a personal history of experience and growth, the foundation phase of
      nursing, the developmental phase of nursing, and the historical developments and
      trends in nursing. Prof. Chao's comments reveal how the students missed their
      parents and families, the special friendships among them, and the love and care
      that they received from Chief Mei-Yu Chow and Director Chih-Teh Loo. Tribute is
      paid to their resilience in the face of hardship, and their industry during the
      initial development of the nursing profession. The results also provide the
      suggestions of creating a history of health-care that privileges new meanings
      about military nursing's past and worth.

PMID- 17551894
TI  - Initial formation of nursing philosophies following fundamental clinical
      practice: the experience of male nursing students.
AB  - The purpose of this preliminary study was to explore male nursing students'
      development of nursing philosophies during their fundamental nursing primary
      clinical practice. Purposive sampling was conducted at a department of nursing in
      a university in southern Taiwan between September and October 2005. Researchers
      gave each of the ten subjects selected for this study a semi-structured, in-depth
      interview. The interviews were tape recorded and then transcribed word by word,
      before the content analysis method was used to analyze data. The analysis results
      can be classified into three major categories and various associated themes. The
      first category, professional ambition choice, incorporates the four themes of:
      (1) acceptance of family members' or friends' recommendations; (2) consideration
      of career development factors; (3) eagerness to care for others; and (4)
      limitations imposed by academic achievements. The second category, professional
      gender expectations, incorporates the following four themes: (1) gender role
      revolutions; (2) expectations that "something rare is valued highly" ; (3)
      courage in addressing public misgivings about untraditional professional roles;
      and (4) formulaic gender gap problems. The third category, development of nursing
      philosophy following a primary clinical internship, incorporates the following
      five themes: (1) doubt regarding personal ability to master the complex tasks
      necessary to become a competent nurse; (2) translation of one's field of vision
      from the visible to the invisible; (3) stimulation of learning upon recognition
      of inadequacies; (4) pride in being engaged in the "sacred" work of caring; and
      (5) increased confidence in continuing a nursing career. The results of this
      study may guide nursing educators in promoting an active approach toward training
      and professional education.

PMID- 17551895
TI  - Patterns of physical activity and obesity indices among white-collar men in
      Taiwan.
AB  - The purposes of this study were to identify patterns of physical activity among
      white-collar men in Taiwan and to analyze the relationships between physical
      activity patterns and obesity indices. This cross-sectional survey included 350
      subjects (between 21 and 75 years old). The Monitoring Trends and Determinants of
      Cardiovascular Disease Optional Study of Physical Activity Questionnaire (MOSPA
      Q), developed and published by the World Health Organization (WHO) was used to
      measure subjects' daily energy expenditures attributed to physical activity.
      Obesity indices included body weight, body mass index (BMI), waist/hip ratio
      (WHR), body fat percentage, total cholesterol, triglycerides, high-density
      lipoprotein (HDL), and low-density lipoprotein (LDL). Three patterns of physical
      activity, namely work-oriented, active, and light-active lifestyles, were
      identified through cluster analysis. The work-oriented group reported spending
      the most amount of time on work-related activities (10.5 hours/week). The active
      group spent the most time (1 hour/day) of the three groups on leisure activities.
      The light-active group spent the most time (7 hours/day) of the three groups on
      light activities. Referencing the 150 minutes/week of moderate- intensity
      physical activity recommended by the US Centers for Disease Control and
      prevention (CDC) for health gain as a cut-off point, 1.1%, 15.2%, and 29.1% of
      subjects in the active, light-active and work-oriented groups, respectively,
      failed to achieve this minimal level. Those in the work-oriented group
      categorized in high work-overload and prevalent inactivity situations returned
      the worst obesity indices (Body weight, BMI, WHR, and body fat percentages)
      adjusted by age.

PMID- 17551896
TI  - The process of assisting behavior modification in a child with attention-deficit
      hyperactivity disorder.
AB  - Attention Deficit Hyperactivity Disorder (ADHD) is a common psychological disease
      among children. The purpose of this study was to describe the process of
      assisting with behavior modification in a child with ADHD. The patient had
      undergone medical treatment for a year with no obvious effect. With the guidance
      of other professional people, the child's teachers and nursing instructors, the
      researchers proceeded with behavioral modification in conjunction with medication
      for another year. The medication treatment followed doctors' prescriptions, and,
      as regards the behavioral treatment, doctors and experts drafted and decided the
      content of the behavioral contract. The main basic techniques were skillful
      reinforcement and punishment. Then, via interviews with his parents and teachers,
      information was obtained that provided an understanding of the patient's
      condition and progress. It was found that the improvements were very significant.
      On the basis of the research results, the researchers submit that: (1) drug
      treatment combined with behavioral treatment apparently improves the daily
      behaviors of hyperactive children; (2) good communication with parents and
      psychological preparation are the most critical keys to the success of
      substantial behavioral improvement among hyperactive children; (3) establishment
      and integration of social resources, including provision of transitional
      parenting education solutions, and cooperation and sound interaction from school
      teachers, which fosters consolidated team work, are the critical factors to
      behavioral improvement among hyperactive children.

PMID- 17551897
TI  - A feasible method to enhance and maintain the health of elderly living in long
      term care facilities through long-term, simplified tai chi exercises.
AB  - Practicing Tai Chi offers the potential to enhance the physical and mental health
      of older adults. Identifying a feasible way to encourage regular Tai Chi practice
      is essential if Tai Chi is to be promoted as a long-term, daily activity for
      elderly care facility residents. The purpose of this study was to test the
      effectiveness and feasibility of using an audiovisual, simplified Tai Chi
      exercise module to enhance and maintain the health of long-term care facility
      residents. A quasi-experimental, one-group, time-series design was used. Data
      were collected six times (twice before the intervention; four times after
      intervention started) at three-month intervals. Fifty-one elderly male subjects
      were recruited by convenience sampling. A 50-minute Simplified Tai-Chi Exercise
      Program (STEP) was implemented in two small groups three times a week for 12
      months. During the first six-month period, participants received guidance from an
      actual instructor. During the second six-month period, guidance was delivered via
      a video tape and displayed on a television screen. Results indicated that
      participants' physical health (cardio-respiratory function, lower body
      flexibility, and hand-gripping strength) and mental health (quality of sleep) had
      both improved significantly six months after intervention started, with
      improvements maintained throughout the end of the 12-month study (all p values <
      .05). Instructor-led STEP training followed by practice using appropriate
      audiovisual aids represents a feasible and effective method to implement a long
      term activity program in long-term elderly care facilities.

PMID- 17551898
TI  - The monthly thought of the Editor: ADQI, AKIN, and beyond.

PMID- 17551899
TI  - Improving outcomes from acute kidney injury (AKI): Report on an initiative.
AB  - Acute Kidney Injury (AKI) is a complex disorder for which currently there is no
      accepted definition. We describe an initiative to develop uniform standards for
      defining and classifying AKI and establish a forum for multidisciplinary
      interaction to improve care for patients with, or at risk for AKI. Members
      representing key societies in critical care and nephrology along with additional
      experts in adult and pediatric AKI participated in a 2-day conference in
      Amsterdam in September 2005 to draft consensus recommendations for diagnosing and
      staging AKI. This report describes the proposed diagnostic and staging criteria
      for AKI and the formation of a multidisciplinary collaborative network.

PMID- 17551900
TI  - A new method to evaluate patient characteristic response to ultrafiltration
      during hemodialysis.
AB  - BACKGROUND: Several factors are involved in the pathogenesis of dialysis
      discomfort interfering with optimal fluid removal and reducing the efficacy of
      the treatment; the most important one is a decrease in blood volume caused by an
      imbalance between ultrafiltration (UF) and plasmarefilling (PR) rates.
      OBJECTIVES: This study is aimed at devising a method to tailor the dialysis
      therapy to each individual patient, by analyzing the relationship between PR and
      UF during the sessions in stable patients and widening the knowledge of fluid
      exchanges during the treatment. METHODS: Thirty stable patients undergoing
      maintenance hemodialysis were enrolled. Three dialysis sessions were monitored
      for each patient; systemic pressure, blood composition, blood volume % variation,
      weight loss and conductivity were recorded repeatedly. A Plasma Refilling Index
      (PRI), defined and calculated by means of parameters measured throughout the
      dialysis, was introduced as a novel instrument to study plasma refilling
      phenomena. Results. The PRI provides understanding of patient response (in terms
      of plasma refilling) to the set UF. In the monitored sessions, the PRI trend is
      found to be characteristic of each patient; a PRI course that is at variance with
      the characteristic trend is a signal of inadequate or unusual dialysis
      scheduling. Moreover, statistical analysis highlights two different PRI trends
      during the first hour and during the rest of the treatment, suggesting the
      presence of different treatment phases. CONCLUSION: The main advantage of the PRI
      index is that it is non-invasive peculiar to each patient and easy to compute in
      a dialysis routine based on online data recorded by the monitor. A deviation from
      the characteristic trend may be a warning for the clinician. The analysis of the
      PRI trend also suggests how to modulate UF as a function of interstitial to
      intravascular fluid removal balance during dialysis.

PMID- 17551901
TI  - Beta2-microglobulin removal and plasma albumin levels with high cut-off
      hemodialysis.
AB  - PURPOSE: beta2-microglobulin (beta2MG) is pivotal to the pathogenesis of dialysis
      related amyloidosis. We compared the effects of high cut-off hemodialysis (HCO
      HD) with those of standard high-flux hemodialysis (HF-HD) regarding the
      concentration and clearance of beta2MG and albumin. DESIGN: We enrolled ten
      patients with acute renal failure in a double-blind, cross-over, randomized
      controlled trial. PROCEDURES: Each patient received four hours of HCO-HD
      (estimated in vivo cutoff 50-60 kDa) and four hours of HF-HD (estimated in vivo
      cutoff 15-20 kDa) in random order. Statistical methods and outcome measures: As
      data lacked normal distribution, we used nonparametric statistical analysis.
      Plasma and dialysate concentrations of beta2MG and albumin were measured at
      baseline and after four hours of each study treatment. MAIN FINDINGS: We found
      significantly greater diffusive beta2MG clearances for HCO-HD compared to HF-HD
      (at the start: 71.8 ml/min vs. 5.1 ml/min; P=0.008 and at the end: 68.8 ml/min
      vs. 5.7 ml/min; P=0.008). We found a reduction in plasma beta2MG concentrations
      of -31.6% during HCO-HD compared to an increase by 25.7% during HF-HD; P=0.008.
      At baseline (HCO-HD: 26.0 g/L vs. HF-HD: 26.5 g/L), and at the end of both
      treatments, plasma albumin concentrations were comparable (HCO-HD: 25.5 g/L vs.
      HF-HD: 26.5 g/L; P=0.25). During HCO-HD, albumin clearance was 1.9 ml/min at the
      start and decreased significantly to 0.8 ml/min at the end; P=0.008. HF-HD had an
      albumin clearance of 0.01 ml/min. CONCLUSIONS: HCO-HD was more effective in
      decreasing plasma beta2MG concentrations than standard HF-HD and did not reduce
      plasma albumin levels. Further studies of HCO-HD in the treatment of dialysis
      related beta2MG accumulation appear warranted.

PMID- 17551902
TI  - Endothelial dysfunction in patients with severe acute pancreatitis: improved by
      continuous blood purification therapy.
AB  - OBJECTIVES: Endothelium dysfunction is one of the critical pathophysiologic
      disorders in patients with severe acute pancreatitis (SAP). To investigate the
      effect of continuous blood purification (CBP) on endothelial function, we
      conducted a prospective study of 20 patients with SAP, 9 of whom had evidence of
      sepsis. METHODS: All patients underwent CVVH for 72 h. Soluble E-selectin (sE
      selectin), soluble thrombomodulin, permeability of the endothelial monolayer, and
      endothelial intracellular calcium ([Ca2+]i ) levels were used as the markers for
      the assessment of endothelial function and the effect of CBP therapy in patients
      with SAP. Blood samples were taken from the patients at 0, 2, 12, 24, 48, and 72
      h during CVVH therapy. sE-selectin and thrombomoduiln were measured by ELISA. The
      endothelial permeability and activation were evaluated using cultured endothelial
      monolayer and intracellular Ca2+ concentration. RESULTS: The results showed that
      during CVVH treatment, the hemodynamics and mean arterial pressure (MAP) were
      stable. The Acute Physiology and Chronic Health Evaluation (APACHE) II score was
      improved significantly after CVVH. Endothelial dysfunction was evident in
      patients with SAP as compared to normal controls. Patients with SAP had increased
      levels of sE-selectin, endothelial permeability and intracellular [Ca2+]i , which
      was higher in patients with sepsis than in those without sepsis. The level of
      thrombomodulin showed a tendency to increase; however, these changes were not
      significant between SAP patients and controls. After CBP treatment, sE-selectin
      levels substantially decreased in all patients. CBP treatment also significantly
      diminished the endothelial permeability and decreased the intracellular [Ca2+]
      concentration. CONCLUSIONS: These data demonstrate that endothelial dysfunction
      is present in patients with SAP and the degree of endothelial damage may be
      correlated with the disease severity. CBP therapy can not only improve the
      general conditions, as measured by the APACHE II score, but also effectively
      improve endothelial dysfunction.

PMID- 17551903
TI  - Plasma filtration on mediators of thrombotic microangiopathy: an in vitro study.
AB  - OBJECTIVES: Sepsis-induced thrombotic microangiopathy is successfully treated by
      plasma exchange therapy. However, certain putative mediators of thrombotic
      microangiopathy may not be removed by plasma filtration. METHODS: We conducted an
      in vitro study to determine whether plasma filtration can remove ultralarge von
      Willebrand factor (ULvWF) multimers and other mediators. In separate experiments,
      human umbilical venous endothelial cell (HUVEC) supernatant enriched with ULvWF
      or human whole blood was passed through a therapeutic plasma exchange (TPE 2000,
      PRISMA) filter and samples were taken for measurement of ULvWF, vWF ristocetin
      cofactor, vWF antigen and PAI-1. RESULTS: The sieving coefficients for vWF and
      PAI-1 were above 0.9. The ULvWF was gradually eliminated, and nearly disappeared
      after four circulations. CONCLUSION: The TPE 2000 filter can directly remove
      potential mediators of sepsis-induced thrombotic microangiopathy.

PMID- 17551904
TI  - ECG-triggered muscular counterpulsation for treatment of low cardiac output.
AB  - BACKGROUND: Skeletal muscular counterpulsation (MCP) has been used as a new
      noninvasive technique for treatment of low cardiac output. The MCP method is
      based on ECG-triggered skeletal muscle stimulation. The purpose of the present
      study was to evaluate acute hemodynamic changes induced by MCP in the
      experimental animal. METHODS: Eight anaesthetized pigs (43+/-4 kg) were studied
      at rest and after IV a-blockade (10 mg propranolol) before and after MCP.
      Muscular counterpulsation was performed on both thighs using trains (75 ms
      duration) of multiple biphasic electrical impulses with a width of 1 ms and a
      frequency of 200 Hz at low (10 V) and high (30 V) amplitude. ECG-triggering was
      used to synchronize stimulation to a given time point. LV pressure-volume
      relations were determined using the conductance catheter. After baseline
      measurements, MCP was carried out for 10 minutes at low and high stimulation
      amplitude. The optimal time point for MCP was determined from LV pressure-volume
      loops using different stimulation time points during systole and diastole. Best
      results were observed during end-systole and, therefore, this time point was used
      for stimulation. RESULTS: Under control conditions, MCP was associated with a
      significant decrease in pulmonary vascular resistance (-18%), a decrease in
      systemic vascular resistance (-11%) and stroke work index (-4%), whereas cardiac
      index (+2%) and ejection fraction (+6%) increased slightly. Pressure-volume loops
      showed a leftward shift with a decrease in end-systolic volume. After a-blockade,
      cardiac function decreased (HR, MAP, EF, dP/dt max), but it improved with
      skeletal muscle stimulation (HR +10% and CI +17%, EF +5%). There was a
      significant decrease in pulmonary (-19%) and systemic vascular resistance (-29%).
      CONCLUSIONS: In the animal model, ECG-triggered skeletal muscular
      counterpulsation is associated with a significant improvement in cardiac function
      at baseline and after IV a-blockade. Thus, MCP represents a new, non-invasive
      technique which improves cardiac function by diastolic compression of the
      peripheral arteries and veins, with a decrease in systemic vascular resistance
      and increase in cardiac output.

PMID- 17551905
TI  - Enhancement of viability of muscle precursor cells on 3D scaffold in a perfusion
      bioreactor.
AB  - The aim of this study was to develop a methodology for the in vitro expansion of
      skeletal-muscle precursor cells (SMPC) in a three-dimensional (3D) environment in
      order to fabricate a cellularized artificial graft characterized by high density
      of viable cells and uniform cell distribution over the entire 3D domain. Cell
      seeding and culture within 3D porous scaffolds by conventional static techniques
      can lead to a uniform cell distribution only on the scaffold surface, whereas
      dynamic culture systems have the potential of allowing a uniform growth of SMPCs
      within the entire scaffold structure. In this work, we designed and developed a
      perfusion bioreactor able to ensure long-term culture conditions and uniform flow
      of medium through 3D collagen sponges. A mathematical model to assist the design
      of the experimental setup and of the operative conditions was developed. The
      effects of dynamic vs static culture in terms of cell viability and spatial
      distribution within 3D collagen scaffolds were evaluated at 1, 4 and 7 days and
      for different flow rates of 1, 2, 3.5 and 4.5 ml/min using C2C12 muscle cell line
      and SMPCs derived from satellite cells. C2C12 cells, after 7 days of culture in
      our bioreactor, perfused applying a 3.5 ml/min flow rate, showed a higher
      viability resulting in a three-fold increase when compared with the same
      parameter evaluated for cultures kept under static conditions. In addition,
      dynamic culture resulted in a more uniform 3D cell distribution. The 3.5 ml/min
      flow rate in the bioreactor was also applied to satellite cell-derived SMPCs
      cultured on 3D collagen scaffolds. The dynamic culture conditions improved cell
      viability leading to higher cell density and uniform distribution throughout the
      entire 3D collagen sponge for both C2C12 and satellite cells.

PMID- 17551906
TI  - Physical exercise in dialysis patients.

PMID- 17551907
TI  - Fluid balance error in continuous renal replacement therapy: a technical note.
AB  - BACKGROUND: The reliability and safety of continuous renal replacement therapy
      (CRRT) machines have improved, yet there still remains the potential for fluid
      balance errors to occur during treatment. METHODS: In vitro testing of two Kimal
      Hygieia CRRT machines (Plus and Ultima) was performed. Normal saline to simulate
      the blood circuit and standard bicarbonate-based fluid for replacement were used.
      All tests were performed in CVVH mode at four ultrafiltration (UF) rates. The
      testing was based on creation of a voluntary fluid balance error by clamping the
      line that fills the replacement fluid chamber to stop flow to the (simulated)
      patient. The time to alarms and fluid balance errors were recorded. The alarms
      were overridden and the accumulated fluid balance error allowed by the machine
      was determined. RESULTS: The alarm occurred approximately 1 minute after the
      replacement fluid line was clamped at all UF rates. There was no limit to the
      number of times the alarm could be overridden and the accumulated negative fluid
      balance was proportional to the prescribed UF rate. After the replacement fluid
      chamber was allowed to re-fill, the machine attempted to correct the fluid
      deficit and consistently delivered excess fluid to generate a positive fluid
      balance error. CONCLUSIONS: The Hygieia machines appear designed with appropriate
      alarm and safety features. However, simulated fluid balance errors raise caution
      for operators. Clinicians and nurses need to understand the clinical implications
      of alarm overrides. Fluid balance errors caused by failure to acknowledge and
      correct replacement fluid failure alarms may cause harm to patients.

PMID- 17551908
TI  - Prevention of dialysis disequilibrium by use of CVVH.
AB  - OBJECTIVE: Dialysis disequilibrium occurs due to a rapid shift of osmols when
      hemodialysis is used in cases of extreme uremia. Continuous veno-venous
      hemofiltration (CVVH) with citrate anticoagulation may offer a safe method of
      urea reduction. DESIGN: Retrospective, clinical observation. SETTING: Tertiary
      pediatric intensive care unit and nephrology program. Patients. Two males, ages
      10 and 12 years of age. INTERVENTION: CVVH with citrate anticoagulation. RESULTS:
      Three to four day reduction of BUN from 180 mg/dL to 22 mg/dL and from 279 mg/dL
      to 23 mg/dL. CONCLUSION: Slow and safe improvement of severe urea,
      hyperphosphatemia, hypocalcemia, and anemia without untoward side effects.

PMID- 17551909
TI  - Hepatitis C virus infection and rituximab therapy after renal transplantation.
AB  - BACKGROUND: Rituximab, a chimeric monoclonal antibody, has been successfully
      given in various diseases including HCV-associated mixed cryoglobulinemia.
      However, only preliminary data exists on its efficacy and safety after renal
      transplantation. METHODS: We report on a renal transplant recipient with chronic
      hepatitis C who received rituximab therapy for gastric cancer. Four rituximab
      infusions of 375 mg/m(2) were given. RESULTS: Rituximab therapy was complicated
      by cholestatic hepatitis C with very high HCV RNA levels; liver insufficiency
      occurred. The patient developed bacterial pneumoniae and respiratory
      insufficiency was the cause of death. Although other mechanisms cannot be
      excluded, we found that rituximab therapy was implicated in the pathogenesis of
      cholestatic hepatitis C in our patient. CONCLUSIONS: We suggest that rituximab
      therapy may be associated with significant side effects. More experience has to
      be accumulated before any conclusions on efficacy and safety of rituximab therapy
      after RT can be drawn.

PMID- 17551910
TI  - What is the relationship between income inequality and health? Evidence from the
      BHPS.
AB  - Income inequality hypotheses propose that income differentials and/or income
      distributions have a detrimental effect on health. This previously well accepted
      relationship between inequality and health has recently come under scrutiny; some
      claim that it is a statistical artefact, arguing that aggregate level data are
      not sophisticated enough to adequately test for (and discriminate between) their
      existence. Supporters argue that it is a question of estimating the relationship
      using, amongst other things, an appropriate geographical scale. This paper adds
      to the debate by estimating the relationship between income inequality and health
      using individual panel data, exploring the relationship at the regional as well
      as the national level, while attempting to discriminate between the competing
      hypotheses. Pooled, random and fixed effects ordered probit models are exploited
      to estimate the relationship between self-reported health and household income,
      income inequality and relative income. While the estimating regressions find
      support for the absolute income hypothesis, there is no support for the income
      inequality hypothesis or relative income hypothesis, and as such we argue that
      there is limited evidence of an effect of income inequality on health within
      Britain.

PMID- 17551911
TI  - Catalytic enantioselective reduction of beta,beta-disubstituted vinyl phenyl
      sulfones by using bisphosphine monoxide ligands.

PMID- 17551912
TI  - Amphiphilic organic ion pairs in solution: a theoretical study.
AB  - The macroscopic manifestation of hydrophobic interactions for amphiphilic organic
      ion pairs (tetraalkylammonium-anion) has been shown experimentally by measuring
      their association constants and their affinity with the organic phase. Beyond a
      certain size, there is a direct relation between association constants and chain
      lengths in tetraalkylammonium ions. We propose to cast a bridge between these
      results and geometrical properties considered at the level of a single ion pair
      by means of quantum chemistry calculations performed on model systems:
      trimethylalkylammonium-pentyl sulfate instead of tetraalkylammonium-dodecyl
      sulfate. Two limiting cases are considered: head-to-head configurations, which
      yield an optimal electrostatic interaction between polar heads, and parallel
      configurations with a balance between electrostatic and hydrophobic interactions.
      All properties (geometries, complexation energies, and atomic charges) were
      obtained at the MP2 level of calculation, with water described by a continuum
      model (CPCM). Dispersion forces link hydrocarbon chains of tetraalkylammonium
      ions and pentyl sulfate, thus yielding (for the largest ion pairs) parallel
      configurations favored with respect to head-to-head geometries by solute-solvent
      electrostatic interactions. Given the small experimental association energies, we
      probe the accuracy limit of the MP2 and CPCM methods. However, clear trends are
      obtained as a function of chain length, which agree with the experimental
      observations. The calculated monotonic stabilization of ion pairs when the
      hydrocarbon chain increases in length is discussed in terms of electrostatic
      interactions (between ions and between ion pairs and water), dispersion forces,
      and cavitation energies.

PMID- 17551913
TI  - Approaches to the design of better low-dosage gas hydrate inhibitors.

PMID- 17551914
TI  - Periodic mesoporous organosilicas: a type of hybrid support for water-mediated
      reactions.
AB  - Hybrid mesoporous periodic organosilicas (Ph-PMOs) with phenylene moieties
      embedded inside the silica matrix were used as a heterogeneous catalyst for the
      Ullmann coupling reaction in water. XRD, N2 sorption, TEM, and solid-state NMR
      spectroscopy reveal that mesoporous Ph-PMO supports and Pd/Ph-PMO catalysts have
      highly ordered 2D hexagonal mesostructures and covalently bonded organic
      inorganic (all Si atoms bonded with carbon) hybrid frameworks. In the Ullmann
      coupling reaction of iodobenzene in water, the yield of biphenyl was 94%, 34%,
      74% and for palladium-supported Ph-PMO, pure silica (MCM-41), and phenyl-group
      modified Ph-MCM-41 catalysts, respectively. The selectivity toward biphenyl
      reached 91% for the coupling of boromobenzene on the Pd/Ph-PMO catalyst. This
      value is much higher than that for Pd/Ph-MCM-41 (19%) and Pd/MCM-41 (0%),
      although the conversion of bromobenzene for these two catalysts is similar to
      that for Pd/Ph-PMO. The large difference in selectivity can be attributed to
      surface hydrophobicity, which was evaluated by the adsorption isotherms of water
      and toluene. Ph-PMO has the most hydrophobic surface, and in turn selectively
      adsorbs the reactant haloaryls from aqueous solution. Water transfer inside the
      mesochannels is thus restricted, and the coupling reaction of bromobenzene is
      improved.

PMID- 17551915
TI  - Recent developments in asymmetric transfer hydrogenation with Hantzsch esters: a
      biomimetic approach.
AB  - By utilizing Hantzsch esters as the hydrogen source, asymmetric transfer
      hydrogenation of C=C, C=N, and C=O is realized in the presence of an
      organocatalyst or a metal-ligand complex, thus affording versatile chiral
      building blocks in high yields with excellent enantioselectivities under mild
      conditions. A detailed discussion of recent findings and an assessment of this
      biomimetic approach are presented in this review.

PMID- 17551916
TI  - Synthesis of phosphaformamidines and phosphaformamidinates.
AB  - A large-scale synthetic route to a variety of phosphaformamidines and
      phosphaformamidinates, a type of derivative that was not accessible by the
      methods previously known for preparing phosphaamidines and phosphaamidinates, is
      reported. Thermally stable ethyl N-arylformimidates 1 (ArN=CH(OEt), Ar = 2,4,6
      (Me)3Ph or 2,6-(iPr)2Ph) readily reacted with lithium dialkyl- and
      diarylphosphanides to afford the corresponding N-aryl phosphaformamidines in 80
      and 60% yield, respectively, whereas with lithium (aryl)(silyl)phosphanide, the N
      aryl-N-silylphosphaformamidine (60% yield) was obtained. Addition of primary
      lithium arylphosphanides to 1 followed by addition of a stoichiometric amount of
      nBuLi gave rise to the respective phosphaformamidinates (70-88% yield).
      Methanolysis of the products afforded the N-aryl-N-hydrogenophosphaformamidines
      (90-95% yield). The solid-state structure of one of the phosphaformamidinates is
      also presented.

PMID- 17551917
TI  - 2'-N-(pyren-1-yl)acetyl-2'-amino-alpha-L-LNA: synthesis and detection of single
      nucleotide mismatches in DNA and RNA targets.

PMID- 17551918
TI  - A synthetic kiss of death: expressed protein ligation of a ubiquitin-peptide
      conjugate.

PMID- 17551919
TI  - Comparative preclinical activity of the folate-targeted Vinca alkaloid conjugates
      EC140 and EC145.
AB  - EC140 is a water soluble folate conjugate of desacetylvinblastine monohydrazide
      (DAVLBH), which is constructed with an endosome-cleavable acyl hydrazone bond.
      This agent has proven to be active and specific against well established,
      subcutaneous folate receptor (FR)-positive tumors in multiple animal models.
      Recent structure-activity and optimization studies have yielded a disulfide bond
      containing counterpart to EC140, herein referred to as EC145. This new conjugate
      was found to retain high affinity for FR-positive cells, and it produced
      specific, dose-responsive activity in vitro. Comparative in vivo efficacy tests
      confirmed that, like EC140, EC145 displays activity against both syngeneic and
      xenograft tumor models. However, EC145 was found to be more active and better
      tolerated than EC140; hence, more durable complete responses were consistently
      observed in EC145-treated tumor-bearing animals. Furthermore, EC145 was not found
      to be active against a FR-negative tumor model. Additional preclinical studies
      are therefore warranted to better understand EC145's breadth of activity against
      FR-positive tumors.

PMID- 17551920
TI  - A yeast two-hybrid system using Sp17 identified Ropporin as a novel cancer-testis
      antigen in hematologic malignancies.
AB  - Since most intracellular proteins are expressed with their ligands, ligands of
      cancer-testis (CT) antigens may also be CT in their distribution. Applying Sperm
      protein 17 (Sp17) as the bait in a yeast 2-hybrid system of a testicular cDNA
      library, 17 interacting clones were isolated and all encoded Ropporin, a
      spermatogenic cell-specific protein that serves as an anchoring protein for the A
      kinase anchoring protein, AKAP110. Ropporin showed a very restricted normal
      tissue gene expression, detected only in testis and fetal liver. Ropporin mRNA
      could also be detected in tumor cells from patients with multiple myeloma,
      chronic lymphocytic leukemia and acute myeloid leukemia. Interestingly,
      expression of Sp17 did not necessarily predict for the expression of Ropporin
      suggesting that their coexpression in these tumor cells was random rather than
      coordinated. Ropporin gene expression in tumor cells is associated with the
      presence of high titer IgG antibodies against Ropporin, suggesting the in vivo
      translation of the mRNA into protein and the immunogenicity of the protein to the
      autologous hosts. Using a CT antigen as the bait in a yeast 2-hybrid system may,
      therefore, identify novel tumor antigen. Our results also suggest that Ropporin
      is a novel CT antigen in hematologic malignancies.

PMID- 17551922
TI  - Testing equality of several functions: analysis of single-unit firing-rate curves
      across multiple experimental conditions.
AB  - We consider the problem of comparing noisy functions, here trial-averaged
      neuronal firing-rate curves, across multiple experimental conditions. Of interest
      are comparisons both within neurons and also among populations of individually
      recorded neurons. We propose likelihood ratio tests to perform comparisons either
      pointwise or globally over the entire experimental time. A simulation study of
      power demonstrates the strength of these tests even for moderate sample sizes. We
      implement these tests on a group of 233 neurons recorded from primate frontal
      oculomotor cortex, first, to screen for condition-related differential activity
      and, second, to search for neurons displaying interesting time-locked features
      that vary with condition.

PMID- 17551921
TI  - Activation of PI3K-Akt signaling pathway promotes prostate cancer cell invasion.
AB  - Activated phosphoinositide 3-kinase (PI3K) and its downstream target Akt/PKB are
      important signaling molecules and key survival factors involved in the control of
      cell proliferation, apoptosis and oncogenesis. We investigated the role of the
      PI3K-Akt signaling pathway in the invasion of prostate cancer cell lines and
      activation of this pathway in primary human prostate tumors. Treatment of human
      prostate cancer cells viz. LNCaP, PC-3 and DU145 with PI3K pharmacological
      inhibitor, LY294002, potentially suppressed the invasive properties in each of
      these cell lines. Restoration of the PTEN gene to highly invasive prostate cancer
      PC-3 cells or expression of a dominant negative version of the PI3K target, Akt
      also significantly inhibited invasion and downregulated protein expression of
      urokinase-type plasminogen activator (uPA) and matrix metalloproteinase (MMP)-9,
      markers for cell invasion, indicating a central role of the PI3K-Akt pathway in
      this process. Immunoblot analysis of PI3K and total/activated levels of Akt
      showed increased protein levels of catalytic (p110alpha/beta) and regulatory
      (p85) subunits of PI3K and constitutive Akt activation in high-grade tumors
      compared to low-grade tumor and benign tissue. Immunohistochemical analyses
      further confirmed a progressive increase in p-Akt (p-Ser473) levels but not of
      total-Akt (Akt1/2) in cancer tissues compared to benign specimens. A successive
      increase in p-Akt expression was further noted in specimens serially obtained
      from individuals with time-course disease progression. Taken together, these
      results suggest that aberrant activation of PI3K-Akt pathway may contribute to
      increased cell invasiveness and facilitate prostate cancer progression.

PMID- 17551923
TI  - Sexual dysfunction and physicians' perception in medicated patients with major
      depression in Taiwan.
AB  - Although prevalent during antidepressant treatment, sexual dysfunction (SD) is
      frequently ignored by both physicians and patients in Asia. In spite of impact of
      SD on medicated patients with major depression, sexual issues and illness remain
      a forbidden topic for most Asian people. The aims of this study were to: (1)
      estimate the prevalence of SD among stable outpatients taking different
      antidepressants in Taiwan; (2) investigate the factors related to SD; (3) compare
      physician-perceived with patient-reported prevalence rates of antidepressant
      associated SD; and (4) study the differences of SD among antidepressant
      subgroups. In this cross-sectional observational study, 125 medicated patients
      with major depression were recruited. Patients were assessed using the Changes in
      Sexual Functioning Questionnaire (CSFQ), Taiwanese Depression Questionnaire
      (TDQ), Quality of Life Index (QOL), and neuroticism scores in the Maudsley
      Personality Inventory (MPI). Sixty-two physicians completed the Physician
      Antidepressant Experience Questionnaire. The estimated prevalence rate of SD was
      53.6% (95% CI = 44.9-62.3%) in medicated patients with major depression. There
      were no significant differences in prevalence rate of SD among different
      antidepressants. The SD subgroup had poorer quality of life and lower moods than
      the non-dysfunction subgroup. An underestimation of the prevalence of SD by
      physicians was noted. Because antidepressant-associated SD is highly prevalent
      and seriously underestimated by physicians, greater physicians' recognition and
      better patients' education are imperative when prescribing antidepressants.

PMID- 17551924
TI  - Further delineation of the phenotype resulting from BRAF or MEK1 germline
      mutations helps differentiate cardio-facio-cutaneous syndrome from Costello
      syndrome.
AB  - Because Cardio-facio-cutaneous (CFC) syndrome has significant phenotypic overlap
      with Costello syndrome, it may be difficult to establish the diagnosis on a
      clinical basis. The recent discoveries of germline HRAS mutations in patients
      with Costello syndrome and mutations in BRAF, MEK1, and MEK2 in CFC syndrome
      uncovered the biologic mechanism for the shared phenotypic findings based on the
      close interaction of the affected gene products within the MAP kinase pathway. We
      evaluated a series of patients who were either clinically diagnosed with Costello
      syndrome, or in whom the diagnoses of both Costello and CFC syndromes were
      considered. After excluding mutations in HRAS, we identified eight changes in
      BRAF and five in MEK1. Five mutations are novel, and all changes occurred de novo
      among those triads tested. A review of the clinical abnormalities showed
      important differences between patients with either a BRAF or MEK1 mutation, and
      those previously reported with an HRAS mutation. Statistical significance was
      achieved, despite the relatively small number of patients with BRAF and MEK1
      mutations reported here, for polyhydramnios, growth hormone deficiency and the
      presence of more than one papilloma, which were less common in CFC compared to
      HRAS mutation positive patients. Although both CFC and Costello syndrome are
      characterized by cardiac abnormalities in about three-fourths of patients, the
      pattern of congenital heart defects (CHD), hypertrophic cardiomyopathy (HCM), and
      tachycardia differs somewhat. CHD, especially pulmonic stenosis associated with a
      secundum-type atrial septal defect, are more common in CFC than Costello syndrome
      (P = 0.02). Atrial tachycardia is less frequent in CFC patients with BRAF or MEK1
      mutations, compared to Costello syndrome patients with HRAS mutation (P = 0.04).
      Chaotic atrial rhythm or multifocal atrial tachycardia was observed only in
      Costello syndrome. Malignant tumors have been viewed as characteristic for
      Costello syndrome due to HRAS mutations, however, we report here on a MEK1
      mutation in a patient with a malignant tumor, a hepatoblastoma. Although this
      indicates that the presence of a tumor is not specific for Costello syndrome with
      HRAS mutation, it is noteworthy that the tumor histology differs from those
      commonly seen in Costello syndrome. Based on these clinical differences we
      suggest that patients with BRAF and MEK mutations should be diagnosed with CFC
      syndrome, and the diagnosis of Costello syndrome be reserved for patients with
      HRAS mutations.

PMID- 17551925
TI  - Pressure induces loss of gap junction communication and redistribution of
      connexin 43 in astrocytes.
AB  - Astrocytes, the major glia in the nonmyelinated optic nerve head (ONH), connect
      via gap junctions built of connexin-43 (Cx43) to form a functional syncytium
      allowing communication and control of ionic and metabolic homeostasis of retinal
      ganglion cells (RGCs) axon. We examined gap junction intercellular communication
      (GJIC) by scrape loading assays in human ONH astrocytes exposed to hydrostatic
      (HP) or ambient pressure (CP) in vitro. Immunostaining, immunoprecipitation, and
      immunoblots were used to detect Cx43 distribution and phosphorylation in
      astrocytes exposed to HP with/without EGF receptor (EGFR) tyrosine kinase
      inhibitors AG1478 and AG82 and MAPK inhibitors U0126, PD98059, and SB203580. The
      data indicates that upon exposure to HP, astrocytes decrease GJIC and exhibit
      altered cellular localization and phosphorylation of Cx43. Inhibition of EGFR
      blocked the effects of HP on GJIC and HP-induced Cx43 tyrosine phosphorylation.
      Inhibitors of MAPK- ERK1/2 and -p38 caused partial closure of GJIC under CP and
      HP, which was maintained for 6 h. Inhibition of Big Mitogen-Activated Kinase
      1/ERK5 (BMK1/ERK5) caused partial closure under CP and HP followed by full
      recovery after 6 h. Inhibition of MAPK did not affect the HP-induced increase in
      Cx43 serine 279/282 phosphorylation. We conclude that activation of the EGFR
      pathway in response to HP leads to decrease of GJIC via tyrosine phosphorylation
      of Cx43 in ONH astrocytes. In glaucoma under conditions of elevated intraocular
      pressure (IOP), astrocytes may lose GJIC altering the homeostasis of RGC axons,
      adopting the reactive phenotype, contributing to glaucomatous neuropathy.

PMID- 17551926
TI  - Ferritin accumulation in dystrophic microglia is an early event in the
      development of Huntington's disease.
AB  - Huntington's Disease (HD) is characterized primarily by neuropathological changes
      in the striatum, including loss of medium-spiny neurons, nuclear inclusions of
      the huntingtin protein, gliosis, and abnormally high iron levels. Information
      about how these conditions interact, or about the temporal order in which they
      appear, is lacking. This study investigated if, and when, iron-related changes
      occur in the R6/2 transgenic mouse model of HD and compared the results with
      those from HD patients. Relative to wild-type mice, R6/2 mice had increased
      immunostaining for ferritin, an iron storage protein, in the striatum beginning
      at 2-4 weeks postnatal and in cortex and hippocampus starting at 5-7 weeks. The
      ferritin staining was found primarily in microglia, and became more pronounced as
      the mice matured. Ferritin-labeled microglia in R6/2 mice appeared dystrophic in
      that they had thick, twisted processes with cytoplasmic breaks; some of these
      cells also contained the mutant huntingtin protein. Brains from HD patients
      (Vonsattel grades 0-4) also had increased numbers of ferritin-containing
      microglia, some of which were dystrophic. The cells were positive for Perl's
      stain, indicating that they contained abnormally high levels of iron. These
      results provide the first evidence that perturbations to iron metabolism in HD
      are predominately associated with microglia and occur early enough to be
      important contributors to HD progression.

PMID- 17551927
TI  - Maternally inherited duplication of chromosome 7, dup(7)(p11.2p12), associated
      with mild cognitive deficit without features of Silver-Russell syndrome.
AB  - We report on a familial duplication in the short arm of chromosome 7,
      dup(7)(p11.2p12), present in three generations. The duplication was identified by
      GTG-banding and fluorescence in situ hybridization (FISH) with a whole chromosome
      7 DNA painting probe that verified that the duplicated material originated from
      chromosome 7. The multicolor banding (mBAND) was used to refine the breakpoint
      assignment. The duplication identified in the proband was also present in her son
      and mother. All three carriers have mild cognitive deficiencies. Interstitial
      duplications of the short arm of chromosome 7, although relatively uncommon, have
      been described in association with a variety of clinical features, including
      mental retardation of varying severity. Duplication of the p11.2p13 region on
      chromosome 7 was reported in association with Silver-Russell syndrome (SRS), and
      an overlapping dup(7)(p11.2p14.1)dn was described in an individual with autistic
      disorder. Furthermore, a potentially overlapping maternally transmitted inverted
      duplication, dup(7)(p13p12.2), was reported in patients with cognitive delay.
      These observations and the phenotype of our duplication carriers suggest that
      partial trisomy of the proximal 7p region causes cognitive deficiency. The
      maternal origin of the duplication is of special interest in light of genomic
      imprinting and implication of the 7p11-p13 region in the SRS etiology. Locus
      specific FISH targeting a growth factor receptor binding protein 10 (GRB10), the
      strong candidate for SRS residing at 7p12.2, showed that it is not duplicated in
      our patients. Our study helps refine the SRS critical region on 7p and extends
      our understanding of the clinical manifestations associated with 7p duplications.

PMID- 17551928
TI  - Subclinical photodynamic therapy treatment modifies the brain microenvironment
      and promotes glioma growth.
AB  - Photodynamic therapy (PDT) has been clinically investigated as an adjuvant local
      therapy for brain tumors. Therapeutic interventions intended to promote tumor
      cell death can also promote changes in the tumor microenvironment that could
      favor tumor growth. We have previously shown that PDT can activate pro-angiogenic
      factors in the normal rodent brain. This study seeks to further elucidate the
      effects of subtherapeutic doses of Photofrin-PDT on normal brain and to establish
      a mouse model for studying glioma progression in an environment modified by
      oxidative stress. Photofrin was administered to nude mice, and a defined
      intracranial area was illuminated with laser to deliver an optical dose
      equivalent to 80 J/cm(2). Three and 7 days after PDT, mice were sacrificed and
      brains were fixed and analyzed by immunohistochemistry. PDT treatment resulted in
      transient increase in cell proliferation, associated with a robust activation of
      astrocytes and microglia in the treated region, without causing substantial cell
      death. To test how this modified environment would affect glioma growth, human
      glioblastoma U87 cells were implanted in the PDT-treated hemisphere or in the
      control brain subjected to sham surgery. Significantly larger tumors were
      observed after 3 weeks in the PDT treated brains relative to control treatment.
      Our results indicate that subclinical Photofrin-PDT locally alters the brain
      homeostasis without inflicting significant disruption to the tissue architecture,
      providing a model to study the effects of the microenvironment on glioma growth,
      with implications for the optimization of the clinical use of PDT for brain
      tumors.

PMID- 17551929
TI  - Congenital fibrosis of the extraocular muscles (CFEOM) syndrome associated with
      progressive cerebellar ataxia.
AB  - We here report on a Japanese family with congenital fibrosis of the extraocular
      muscles (CFEOM) syndrome associated with slowly progressive cerebellar ataxia.
      The pedigree indicated autosomal dominant inheritance. All affected individuals
      showed a complete loss of upgaze function with ptosis, and severe or moderate
      restriction of downgaze function probably from the birth. Horizontal gaze
      function was well preserved, except for the eldest patient, who showed both eyes
      almost totally fixed in exotrophic position. The primary vertical and horizontal
      position of each eye varied from patient to patient. Aberrant eye movements were
      observed on attempted upgaze. They showed amblyopia and/or astigmatism, but none
      of them complained of diplopia. Pupillary reactions were normal, and retinal
      pigmentary degeneration or optic atrophy was not observed. These ophthalmological
      findings were consistent with the CFEOM phenotype. The two middle-aged patients,
      but not the two younger patients, showed slowly progressive gait ataxia with
      juvenile onset. Magnetic resonance images of the brain indicated cerebellar
      atrophy in addition to congenital hypoplasia in the cerebellar vermis. Molecular
      genetic analysis provided a negative linkage to the FEOM3 locus. Linkage to the
      FEOM1 locus could not be excluded in our family, but mutation in KIF21A, a major
      cause of the CFEOM1 phenotype, was not detected. We consider that this family may
      broaden the spectrum of the clinical features of CFEOM or the related disorders
      presenting with the CFEOM phenotype.

PMID- 17551930
TI  - Membrane-initiated effects of progesterone on calcium dependent signaling and
      activation of VEGF gene expression in retinal glial cells.
AB  - Neurosteroids, such as progesterone, influence central nervous system development
      and function by regulating a broad spectrum of physiological processes. Here, we
      investigated membrane-initiated actions of progesterone in the retina and
      identified the membrane-associated progesterone receptor component 1 (PGRMC1). We
      found PGRMC1 expressed mainly in retinal Muller glia (RMG) and retinal pigment
      epithelium, and localized uniquely to microsomal and plasma membrane fractions.
      In RMG, membrane-impermeable progesterone conjugate induced calcium influx and
      subsequent phosphatidylinositol 3-kinase-mediated phosphorylation of PKC and ERK
      1/2. Induction by progesterone also led to PKC-dependent activation of VEGF gene
      expression and protein synthesis, suggesting a contribution of membrane-initiated
      hormone effects to VEGF induced neovascularization within retina.

PMID- 17551931
TI  - First-event or marginal estimation of cause-specific hazards for analysing
      correlated multivariate failure-time data?
AB  - In the analysis of multivariate failure-time data, the effect of a treatment or
      an exposure on the hazard of each failure type is sometimes evaluated using only
      the information on the first event that occurs in every individual, ignoring all
      events that follow. A Cox proportional hazards model may be fitted to such data,
      yielding a cause-specific hazard ratio (HR) estimate of the exposure for each
      failure type conditional on surviving all other failure types. However, such an
      estimate would not fully utilize all the available information on event times.
      Alternatively, a marginal approach may be implemented to model the time
      distribution of each failure type beyond the subject's first failure to (any)
      second and later failures. We investigate the performance of these two approaches
      by simulating positive and negative correlated event times from exponential
      distributions. Surprisingly, our results suggest that the first-event-only method
      (when multiple failures are possible) performs as well as the marginal method in
      most practical situations. Generally, for a modest sample size of 400, it is
      possible to achieve at least 85 per cent coverage of the true marginal HR with
      the first-event method. Although the coverage is poor for a correlation of 0.7
      and beyond, such a high correlation between competing event times may be
      biologically rather implausible.

PMID- 17551932
TI  - A comparative study of one-level and two-level semiparametric estimation of
      hemodynamic response function for fMRI data.
AB  - Functional magnetic resonance imaging (fMRI) is emerging as a powerful tool for
      studying the process underlying the working of the many regions of the human
      brain. The standard tool for analyzing fMRI data is some variant of the linear
      model, which is restrictive in modeling assumptions. In this paper, we develop a
      semiparametric approach, based on the cubic smoothing splines, to obtain
      statistically more efficient estimates of the underlying hemodynamic response
      function (HRF) associated with fMRI experiments. The hypothesis testing of HRF is
      conducted to identify the brain regions which are activated when a subject
      performs a particular task. Furthermore, we compare one-level and two-level
      semiparametric estimates of HRF in significance tests for detecting the activated
      brain regions. Our simulation studies demonstrate that the one-level estimates
      combined with a bias-correction procedure perform best in detecting the activated
      brain regions. We illustrate this method using a real fMRI data set and compare
      it with popular methods offered by AFNI and FSL.

PMID- 17551933
TI  - CDG-Id in two siblings with partially different phenotypes.
AB  - We present two sibs with congenital disorder of glycosylation (CDG) type Id. Each
      shows severe global delay, failure to thrive, seizures, microcephaly, axial
      hypotonia, and disaccharidase deficiency. One sib has more severe digestive
      issues, while the other is more neurologically impaired. Each is compound
      heterozygous for a novel point mutation and an already known mutation in the ALG3
      gene that leads to the synthesis of a severely truncated oligosaccharide
      precursor for N-glycans. The defect is corrected by introduction of a normal ALG3
      cDNA. CDG should be ruled out in all patients with severe seizures and failure to
      thrive. (c) 2007 Wiley-Liss, Inc.

PMID- 17551934
TI  - Evidence-based practice in clinical psychology: what it is, why it matters; what
      you need to know.
AB  - The history and meaning of evidence-based practice (EBP) in the health
      disciplines was described to the Council of University Directors of Clinical
      Psychology (CUDCP) training programs. Evidence-based practice designates a
      process of clinical decision-making that integrates research evidence, clinical
      expertise, and patient preferences and characteristics. Evidence-based practice
      is a transdisciplinary, idiographic approach that promotes lifelong learning.
      Empirically supported treatments (ESTs) are an important component of EBP, but
      EBP cannot be reduced to ESTs. Psychologists need additional skills to act as
      creators, synthesizers, and consumers of research evidence, who act within their
      scope of clinical expertise and engage patients in shared decision-making.
      Training needs are identified in the areas of clinical trial methodology and
      reporting, systematic reviews, search strategies, measuring patient preferences,
      and acquisition of clinical skills to perform ESTs.

PMID- 17551935
TI  - Novel tools and resources for evidence-based practice in psychology.
AB  - Given the vast proliferation of scientific research in the behavioral and social
      sciences, there is a growing need for psychologists to be able to access the most
      current, clinically relevant research quickly and efficiently and integrate this
      information into patient care. In response to a similar need within the field of
      medicine, evidence-based medicine took hold in the early 1990s to provide both a
      framework and set of skills for translating research into practice. Since then,
      this method has been adopted by every major health care profession including
      psychology, and is now widely known as evidence-based practice (EBP). In this
      article, the authors present a general overview of the skills required for EBP
      along with an introduction to some of the tools and resources that have been
      developed in other health care professions to support EBP. Using a case example,
      we illustrate how these tools and resources can be applied in psychological
      settings.

PMID- 17551936
TI  - Hydrocele of the canal of Nuck: sonographic and MRI appearances.
AB  - Hydrocele of the canal of Nuck is a rare disorder in females. A 50-year-old
      female presented with the complaint of swelling and occasional pain in the right
      groin. Sonographic examination revealed a proximal dilatation at the inguinal
      canal with a 3-cm ovoid, septated cystic lesion at the distal end. The mass
      appeared as a simple cyst on MRI. Valsalva's maneuver during real-time sonography
      helped differentiate the hydrocele of the canal of Nuck from an inguinal hernia.

PMID- 17551937
TI  - Evidence-based practice in psychology: perceptions of graduate students in
      scientist-practitioner programs.
AB  - The evidence-based practice movement in psychology (EBPP) is a relatively recent
      initiative to improve client care by integrating the best available research
      evidence with clinicians' expertise in the context of patient values and
      preferences. As this movement gains momentum in the field of psychology, training
      programs will likely need to modify their curricula to include training in the
      process of EBPP. An online survey was conducted of clinical psychology graduate
      students in programs that identified themselves as having a scientist
      practitioner or clinical science model (N = 1,195). Understanding of, experiences
      with, attitudes towards, and training in EBPP was assessed. Students had a
      generally favorable view of psychology's move toward EBPP. Although students
      reported a moderate amount of exposure to and experiences with EBPP,
      misunderstandings about the principles of EBPP were prevalent. Compared to
      students planning primarily clinical practice careers, students planning
      primarily clinical research careers were more favorable towards EBPP, expected
      EBPP to be more influential in their future careers, and were more likely to use
      research, but less likely to use client preferences to guide treatment planning.
      Recommendations for modifying training programs to promote EBPP are discussed.

PMID- 17551938
TI  - Implementing elements of evidence-based practice into scientist-practitioner
      training at the University of Nebraska-Lincoln.
AB  - Evidence-based practice (EBP) has become the predominant model of training and is
      emerging as a common model of practice for many non-psychology health care
      professions. Recognizing the relevance of EBP to psychology, the American
      Psychological Association (APA) developed and endorsed an official policy
      statement on EBP for the practice of professional psychology. There is now a
      pressing need to consider ways that EBP can inform scientist-practitioner
      training. The present article proposes clinical competencies associated with the
      practice of EBP, and describes initial efforts to implement elements of EBP into
      training at the University of Nebraska-Lincoln. These efforts have occurred in
      both the classroom and practicum training experiences, and are geared toward
      helping students become more effective users of the evidence base through their
      clinical work. Challenges to the implementation of EBP in clinical psychology
      training are discussed as well.

PMID- 17551939
TI  - Evidence-based practice in psychology: implications for research and research
      training.
AB  - In this article, the author discusses the implications of evidence-based practice
      (EBP) for research and research training in clinical psychology. It is argued
      that EBP provides a useful framework for addressing some heretofore ignored
      problems in clinical research. Advancing evidence-based psychological practice
      will require educators to inject significant new content into research, design,
      and methodology courses and to further integrate research and practicum training.
      The author believes this to be an exciting opportunity for the field, not only
      because it will further psychologists' integration into the interdisciplinary
      health care and research environment, but also because it will provide new tools
      to educate students for capable, not just competent professional activity.

PMID- 17551940
TI  - Barriers and facilitators of evidence-based practice perceived by behavioral
      science health professionals.
AB  - Progress in implementing evidence-based behavioral practices has been slow. A
      qualitative study was performed to characterize the major facilitators and
      barriers to evidence-based practice (EBP) perceived by behavioral professionals.
      Members of professional e-mail listservs were queried and 84 barriers and 48
      facilitators were nominated by 37 respondents. Thematic analysis revealed seven
      themes to describe both barriers and facilitators: (a) training, (b) attitudes,
      (c) consumer demand, (d) logistical considerations, (e) institutional support,
      (f) policy, and (g) evidence. Most frequently cited barriers included negative
      attitudes about EBP and lack of training. Barriers also reflected confusion
      between EBP and the products of EBP (i.e., empirically supported treatments
      [ESTs]). Main facilitators included a growing evidence base. Results suggest that
      uptake of EBP may be facilitated by education and training.

PMID- 17551941
TI  - Evidence-based practice in psychology.
AB  - Evidence-based practice is a growing topic of interest in the field of
      psychology. In 2006, the American Psychological Association (APA) developed a
      formal policy statement on evidence-based practice in psychology (EBPP). It is
      now important for the profession to come to a better understanding about what
      EBPP is (and is not), and to develop a skill set associated with EBPP. The next
      seven articles explore the history of EBPP, elaborate the definition and present
      uses of the term, and provide information relevant to the skill set regarding a
      practice consistent with the evidence-based approach. Many of the articles were
      derived from the 2007 midwinter meeting of the Council of University Directors of
      Clinical Psychology, where the program topic was "Evidence-based Practice: What
      it is, Why It's Important, and What you Need to Know."

PMID- 17551942
TI  - Teaching evidence-based practice: implications for psychology.
AB  - A movement advocating the use of evidence-based practice (EBP) is increasingly
      influencing health care and the practice of psychology. Thus, teaching evidence
      based practice in psychology (EBPP) is critical to the preparation of future
      health service psychologists. In this article, the authors address common myths
      associated with EBP, propose core components involved in teaching EBPP, and
      describe an example of how such training can be incorporated into a professional
      psychology education and training curriculum.

PMID- 17551943
TI  - Ultrasound biomicroscopic appearances of eyelid lesions at 50 MHz.
AB  - PURPOSE: To correlate the ultrasound biomicroscopy (UBM) appearance of eyelid
      lesions with the results of histopathologic examination. METHODS: Fifty-two
      patients with eyelid lesions were evaluated using 50-MHz UBM, and the UBM scans
      were compared with the histopathologic findings. The obscuration of the normal
      lid sonographic layers and invasion into adjacent tissues were criteria
      suggesting malignancy. RESULTS: UBM characteristics of different eyelid lesions
      are presented. The sensitivity of UBM in detecting malignancy ranged from 78% to
      86%, whereas the specificity ranged from 37% to 69%. CONCLUSION: This study of
      eyelid lesions shows that UBM can help differentiate between various benign and
      malignant lid lesions.

PMID- 17551944
TI  - Doppler examination of uteroplacental circulation in early pregnancy: can it
      predict adverse outcome?
AB  - PURPOSE: To determine whether spectral Doppler measurements obtained from
      bilateral uterine, arcuate, radial, and spiral arteries in early gestation
      correlate with adverse pregnancy outcome. METHODS: One hundred five pregnant
      women underwent transvaginal Doppler sonographic examination of uteroplacental
      circulation at 6-12 weeks' gestation. Resistance index (RI) and pulsatility index
      (PI) of bilateral uterine, arcuate, radial, and spiral arteries were measured.
      Diameters of gestational sac (GS) and yolk sac, crown-rump length (CRL), GS-CRL
      difference, and GS/CRL ratio were also recorded. Correlation was made with
      pregnancy outcome. RESULTS: Sixteen women developed adverse pregnancy outcome. In
      these women, right uterine artery PI and RI were significantly higher than in
      women with normal obstetrical outcome. Spiral artery PI and RI values were also
      higher, but the difference was not statistically significant. GS-CRL difference,
      GS/CRL ratio, and yolk sac diameters were significantly lower in this group.
      CONCLUSION: Transvaginal Doppler examination can detect hemodynamic changes in
      uteroplacental circulation associated with subsequent adverse pregnancy outcome.

PMID- 17551945
TI  - Generation of a germ cell-specific mouse transgenic Cre line, Vasa-Cre.
AB  - Cell type-specific genetic modification using the Cre/loxP system is a powerful
      tool for genetic analysis of distinct cell lineages. Because of the exquisite
      specificity of Vasa expression (confined to the germ cell lineage in invertebrate
      and vertebrate species), we hypothesized that a Vasa promoter-driven transgenic
      Cre line would prove useful for the germ cell lineage-specific inactivation of
      genes. Here we describe a transgenic mouse line, Vasa-Cre, where Cre is
      efficiently and specifically expressed in germ cells. Northern analysis showed
      that transgene expression was confined to the gonads. Cre-mediated recombination
      with the Rosa26-lacZ reporter was observed beginning at approximately e15, and
      was >95% efficient in male and female germ cells by birth. Although there was a
      potent maternal effect with some animals showing more widespread recombination,
      there was no ectopic activity in most adults. This Vasa-Cre transgenic line
      should thus prove useful for genetic analysis of diverse aspects of gametogenesis
      and as a general deletor line.

PMID- 17551946
TI  - Cortical functional network organization from autoregressive modeling of local
      field potential oscillations.
AB  - A framework is presented for quantifying functional network organization in the
      brain by spectral analysis based on autoregressive modeling. Local field
      potentials (LFPs), simultaneously recorded from distributed sites in the cerebral
      cortex of monkeys, are treated as signals generated by local neuronal assemblies.
      During the delay period of a visual pattern discrimination task, oscillatory
      assembly activity is manifested in the LFPs in the beta-frequency range (14-30
      Hz). Coherence analysis has shown that these oscillations are phase synchronized
      in functional networks in the sensorimotor cortex in relation to maintenance of
      contralateral hand position, and in the visual cortex in relation to anticipation
      of the visual stimulus. Granger causality analysis has revealed information flow
      in the sensorimotor network that is consistent with a peripheral sensorimotor
      feedback loop, and in the visual network that is consistent with top-down
      anticipatory modulation of assemblies in the primary visual cortex.

PMID- 17551947
TI  - Pd-catalyzed asymmetric allylic substitution reactions using P-chirogenic
      diaminophosphine oxides: DIAPHOXs.
AB  - This paper describes the development of a new class of chiral phosphorus ligand:
      aspartic acid-derived P-chirogenic diaminophosphine oxides, DIAPHOXs, and their
      application to several Pd-catalyzed asymmetric allylic substitution reactions. Pd
      catalyzed asymmetric allylic alkylation was initially examined in detail using
      diaminophosphine oxides 1a, resulting in the highly enantioselective construction
      of quaternary stereocenters. Mechanistic investigations revealed that 1a is
      activated by N,O-bis(trimethylsilyl)acetamide-induced tautomerization to afford a
      trivalent diamidophosphite species 12, which functions as the actual ligand.
      Furthermore, asymmetric allylic amination was examined using Pd-DIAPHOX catalyst
      systems, providing a variety of chiral allylic amines.

PMID- 17551948
TI  - Identification of a novel fusion gene MLL-MAML2 in secondary acute myelogenous
      leukemia and myelodysplastic syndrome with inv(11)(q21q23).
AB  - We have identified a novel fusion partner of MLL, namely the mastermind like 2
      (MAML2 gene), in secondary acute myeloid leukemia (AML) and myelodysplastic
      syndrome (MDS) with inv(11)(q21q23). RT-PCR and sequencing revealed that exon 7
      of MLL was fused to exon 2 of MAML2 in the AML and MDS cells. The inv(11)(q21q23)
      results in the creation of a chimeric RNA encoding a putative fusion protein
      containing 1,408 amino acids from the NH2-terminal part of MLL and 952 amino
      acids from the COOH-terminal part of MAML2. The NH2-terminal part of MAML2, a
      basic domain including a binding site of the intracellular domain of NOTCH, was
      deleted in MLL-MAML2. MLL-MAML2 in secondary AML/MDS and MECT1-MAML2 in
      mucoepithelioid carcinoma, benign Wartin's tumor, and clear cell hidradenoma
      consist of the same COOH-terminal part of MAML2. A luciferase assay revealed that
      MLL-MAML2 suppressed HES1 promoter activation by the NOTCH1 intracellular domain.
      MAML2 involving a chimeric gene might contribute to carcinogenesis in multiple
      neoplasms by the disruption of NOTCH signaling.

PMID- 17551949
TI  - Control of helix sense in protein-mimicking backbone by the noncovalent chiral
      effect.
AB  - We have reviewed our previous work regarding induction or control of a peptide
      helix sense through chiral stimulus to the peptide chain terminus. An optically
      inactive 3(10)-helix designed mainly with unusual alpha-amino acid residues was
      commonly employed. Such an N-terminal-free peptide generates a preferred helix
      sense by chiral acid molecule. A helix sense pre-directed in chiral sequence is
      also influenced or controlled by the chiral sign of such external molecule. Here
      free amide groups in the 3(10)-helical N-terminus participate in the formation of
      a multipoint coordinated complex. The terminal asymmetry produces the noncovalent
      chiral domino effect (NCDE) to influence the whole helix sense. The NCDE-mediated
      control of helicity provides the underlying chiral nature of protein-mimicking
      helical backbones: notably, chiral recognition at the terminus and modulation of
      helical propensity through chiral stimulus. The above items from our previous
      reports have been outlined and reviewed together with their significance in
      biopolymer science and chiral chemistry.

PMID- 17551950
TI  - "Are we there yet?".

PMID- 17551951
TI  - Vomiting-again?

PMID- 17551953
TI  - Severe tophaceous gout.

PMID- 17551954
TI  - Left atrium myxosarcoma: an exceptional cardiac malignant primary tumor.
AB  - We report the case of a 32-year-old patient with a left atrium myxosarcoma,
      presenting with congestive heart failure. It is a rare cardiac malignant primary
      tumor that seems to derive from the same cellular line as myxomas, but the
      prognosis is very different. These tumors present local recidives and distance
      metastasis, so the mean survival is about 1 year, independent of any
      therapeutical option.

PMID- 17551955
TI  - A rare coronary anomaly: double right coronary artery.

PMID- 17551956
TI  - Pod1 induces myofibroblast differentiation in mesenchymal progenitor cells from
      mouse kidney.
AB  - The class II basic helix-loop-helix (bHLH) transcription factor Pod1 is expressed
      in mesenchymal cells including smooth muscle progenitors during development and
      in interstitial cells in adult organs. To determine the role of Pod1 in
      mesenchymal cell smooth muscle and myofibroblast differentiation, we examined a
      kidney progenitor cell line (4E) that endogenously expresses Pod1 and its class I
      bHLH partner E2A. In vitro-translated Pod1 co-immunoprecipitated E2A and
      increased E2A binding to a calponin promoter E-box sequence as determined by an
      electrophoresis mobility shift assay (EMSA). Overexpression of Pod1 and E2A
      resulted in increased smooth muscle and myofibroblast gene expression including
      calponin, SM22alpha, alphaSMA, fibronectin, and connective tissue growth factor
      (CTGF) compared with overexpression of E2A alone. Suppression of Pod1 by siRNA
      resulted in increased cell proliferation and reduced expression of alphaSMA,
      fibronectin, and CTGF, and myofibroblast secreted proteins including pro-fibrotic
      cytokines and inhibitors of matrix metalloproteinases. Examination of the
      signaling pathways for myofibroblast differentiation including Rho/Rho kinase and
      p38 MAPK showed that inhibition of actin polymerization by Rho kinase inhibitors
      decreased nuclear Pod1 levels while inhibition of p38 MAPK decreased Pod1
      expression. These results indicate that Pod1 increases myofibroblast
      differentiation in combination with E2A and promotes a myofibroblast phenotype in
      mesenchymal progenitor cells.

PMID- 17551957
TI  - Some thoughts about recent hypertension trials.

PMID- 17551958
TI  - Treatment of mechanical valve thrombosis during pregnancy.
AB  - Pregnant patients with mechanical valves require anticoagulation. The risk of
      bleeding and embryopathy associated with oral anticoagulation must be weighed
      against the risk of valve thrombosis. In the presence of a mechanical valve
      thrombosis, an appropriate treatment modality must be selected, as it is critical
      for the health of mother and fetus. In this review, we present a pregnant patient
      with mechanical valve thrombosis (MVT) who underwent thrombolytic therapy,
      subsequent anticoagulation according to available guidelines, and delivered a
      healthy baby at full term.

PMID- 17551959
TI  - Cardiac manifestations of parasitic infections part 3: pericardial and
      miscellaneous cardiopulmonary manifestations.
AB  - This is part three of a three-part series discussing parasites of the heart. In
      this section, we present an overview on parasitic diseases involving
      predominantly the pericardium and other miscellaneous cardiopulmonary
      manifestations such as some pulmonary hypertension syndromes and endomyocardial
      fibrosis.

PMID- 17551961
TI  - Robert Earl Beamish.

PMID- 17551962
TI  - Akt signaling regulates actin organization via modulation of MMP-2 activity
      during chondrogenesis of chick wing limb bud mesenchymal cells.
AB  - Endochondral ossification is initiated by the differentiation of mesenchymal
      precursor cells to chondrocytes. This process is characterized by a strong
      interdependence of cell shape and cytoskeletal organization accompanying the
      onset of chondrogenic gene expression, but the molecular mechanisms mediating
      these interactions are not known. In this study, we hypothesized that the
      activation of matrix metalloproteinase (MMP)-2 would be involved in the
      reorganization of the actin cytoskeleton and that this would require an Akt
      dependent signaling pathway in chick wing bud mesenchymal cells. The
      pharmacological inhibition of Akt signaling resulted in decreased
      glycosaminoglycan synthesis and reduced the level of active MMP-2, leading to
      suppressed cortical actin organization which is characteristic of differentiated
      chondrocytes. In addition, the exposure of cells to bafilomycin A1 reversed these
      chondro-inhibitory effects induced by inhibition of Akt signaling. In conclusion,
      our data indicate that Akt signaling is involved in the activation of MMP-2 and
      that this Akt-induced activation of MMP-2 is responsible for reorganization of
      the actin cytoskeleton into a cortical pattern with parallel rounding of
      chondrogenic competent cells.

PMID- 17551963
TI  - Initial heart rate and systolic blood pressure predict outcomes in chronic heart
      failure patients who are evaluated for cardiac transplant.
AB  - BACKGROUND: Heart rate (HR) and systolic blood pressure (SBP) are currently not
      considered among common clinical indicators of prognosis in patients referred for
      heart transplant (Htx). We sought to determine whether an initial hemodynamic
      profile of HR and SBP could be used to predict outcomes in chronic heart failure
      patients evaluated for Htx. METHODS: We analyzed the medical records of patients
      evaluated for Htx and obtained demographic and clinical data collected at the
      initial transplant clinic visit or inpatient encounter. We assigned patients to
      groups based on their HR and SBP. Groups were compared after follow-up for
      differences in freedom from death or Htx. RESULTS: From 1999 to 2003, 400
      consecutive patients were considered by the local Htx medical review board. The
      median duration of follow-up was 26 months (interquartile range 1 to 45 months).
      Patients with initial >or= 90 beats per minute (bpm) and initial SBP < 100 mmHg
      ((n = 34) had worse New York Heart Association functional class (p=0.02), lower
      cardiac output ((p =0.02 ), and greater hyponatremia (>0.001;). These patients
      were more likely to be hospitalized at the time of referral (p >0.001) and more
      likely to have experienced death or Htx during follow-up than patients with other
      hemodynamic profiles (p = 0.001). CONCLUSIONS: A hemodynamic profile of HR and
      SBP can be used with other prognostic indicators to identify high-risk patients
      at the time of initial evaluation for Htx.

PMID- 17551964
TI  - Traditional risk factors and acute myocardial infarction in patients hospitalized
      with cocaine-associated chest pain.
AB  - BACKGROUND: Cocaine causes coronary artery constriction and may cause acute
      myocardial infarction (AMI). The role of traditional coronary risk factors in
      cocaine-associated myocardial infarction is unclear. HYPOTHESIS: We hypothesized
      that traditional risk factors play a major role in predicting AMI in patients
      admitted with cocaine-associated chest pain METHODS: After reviewing 165
      admissions for chest pain in patients with a history of recent cocaine use and/or
      a positive drug screen from January 2001 to December 2004, we identified 151
      patients with information available on at least 6 of the following 7 risk
      factors: gender, hypertension, hyperlipidemia, diabetes, smoking, family history
      of coronary artery disease (CAD) and known CAD. AMI was diagnosed using WHO
      criteria. A risk score was calculated on the basis of the number of risk factors,
      gender and age. Association of AMI was evaluated with the individual risk factors
      and with the risk score. RESULTS: AMI was identified in 21 patients (14%). All
      patients diagnosed with AMI were smokers. Continuous risk score (p < 0.0001),
      highest vs. lowest quartile of risk score (p = 0.007), known CAD, age,
      hyperlipidemia and family history of CAD were individually associated with the
      diagnosis of AMI (p>or=0.05). Each quartile of risk score was associated with
      increased odds of the diagnosis of AMI and score of 8 or higher was statistically
      significant. CONCLUSION: Several traditional risk factors are associated with the
      diagnosis of AMI among patients hospitalized with cocaine-associated chest pain
      and increasing risk factor score was associated with increasing odds of AMI
      diagnosis.

PMID- 17551965
TI  - Effect of nitric oxide donor and gamma irradiation on MAPK signaling in murine
      peritoneal macrophages.
AB  - Irradiation (IR) of cells is known to activate enzymes of mitogen activated
      protein kinase (MAPK) family. These are known to be involved in cellular response
      to stress and are determinants of cell death or survival. When radiotherapy is
      delivered to malignant cells, macrophages, being radioresistant, survive, get
      activated, and produce large amounts of nitric oxide. As a result of activation
      they recognize and phagocytose tumor and normal cell apoptotic bodies leading to
      tumor regression. In this study, the MAPK signaling in peritoneal macrophages was
      investigated which plays an important role in its various functions, in an
      environment which is predominantly nitric oxide, as is after IR. The behavior of
      macrophages in such an environment was also looked at. The three MAPK (ERK1/2,
      p38, and JNK) respond differently to Sodium nitroprusside (SNP) alone or IR
      alone. All the three were activated following IR but only JNK was activated
      following SNP treatment. Surprisingly, when both the stresses were given
      simultaneously or one after the other, this differential response was lost and
      there was a complete inhibition of phosphorylation of all the three MAPKs,
      irrespective of the order of the two insults (IR and SNP). The noteworthy
      observation was that despite the complete inhibition of MAPK signaling there was
      no effect on either the viability or the phagocytic efficiency of peritoneal
      macrophages.

PMID- 17551967
TI  - Does heart failure therapy differ according to patient sex?
AB  - OBJECTIVES: To assess differences in clinical characteristics, treatment and
      outcome between men and women with heart failure (HF) treated at a
      multidisciplinary HF unit. All patients had their first unit visit between August
      2001 and April 2004. PATIENTS: We studied 350 patients, 256 men, with a mean age
      of 65 +/- 10.6 years. In order to assess the pharmacological intervention more
      homogeneously, the analysis was made at one year of follow-up. RESULTS: Women
      were significantly older than men (69 +/- 8.8 years vs. 63.6 +/- 10.9 years, p <
      0.001). Significant differences were found in the HF etiology and in co
      morbidities. A higher proportion of men were treated with ACEI (83% vs. 68%, p <
      0.001) while more women received ARB (18% vs. 8%, p = 0.006), resulting in a
      similar percentage of patients receiving either of these two drugs (men 91% vs.
      women 87%). No significant differences were observed in the percentage of
      patients receiving beta-blockers, loop diuretics, spironolactone, anticoagulants,
      amiodarone, nitrates or statins. More women received digoxin (39% vs. 22%, p =
      0.001) and more men aspirin (41% vs. 31%, p = 0.004). Carvedilol doses were
      higher in men (29.4 +/- 18.6 vs. 23.8 +/- 16.4, p = 0.03), ACEI doses were
      similar between sexes, and furosemide doses were higher in women (66 mg +/- 26.2
      vs. 56 mg +/- 26.2, p < 0.05). Mortality at 1 year after treatment analysis was
      similar between sexes (10.4% men vs. 10.5% women). CONCLUSIONS: Despite
      significant differences in age, etiology and co-morbidities, differences in
      treatment between men and women treated at a multidisciplinary HF unit were
      small. Mortality at 1 year after treatment analysis was similar for both sexes.

PMID- 17551966
TI  - Effects of insulin dependence on inflammatory process, thrombotic mechanisms and
      endothelial function, in patients with type 2 diabetes mellitus and coronary
      atherosclerosis.
AB  - BACKGROUND: Type 2 diabetes mellitus (T2DM) is characterized by endothelial
      dysfunction, increased thrombogenicity and abnormal inflammatory response.
      HYPOTHESIS: We hypothesizsed that insulin dependence/exogenous insulin
      administration may affect thrombotic/inflammatory status and endothelial function
      in patients with T2DM and coronary artery disease (CAD). METHODS: Fifty-five
      patients with T2DM + CAD (26 insulin-treated (INS) and 29 under oral biguanide +
      sulphonylurea (TABL)) were recruited. Endothelial function was assessed by gauge
      strain plethysmography, and serum levels of inflammatory and thrombotic markers
      were determined by enzyme linked immunosorbent assay. RESULTS: There was no
      significant difference in endothelium-dependent dilation (EDD) between the study
      groups, while EDD was correlated with fasting glucose levels in both INS (r = -
      0.776, p = 0.0001) and TABL (r = - 0.702, p = 0.0001). Patients in INS group had
      higher levels of interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-alpha),
      monocyte chemoattractant protein (MCP-1) and vascular cell adhesion molecule
      (sVCAM-1), compared to TABL. However, TNF-alpha was negatively correlated with
      protein C (PrtC) only in INS (r = - 0.726, p = 0.01) but not in TABL group (r = -
      0.066, p = 0.738). Similarly, sVCAM-1 was correlated with PrtC only among INS
      patients (r = - 0.451, p = 0.046) but not in TABL (r = 0.069, p = 0.727). In
      multivariate analysis, insulin dependence was a predictor of IL-6, TNF-alpha, MCP
      1 and sVCAM-1 levels independently from the patients' demographic
      characteristics, the angiographic extend of CAD or the duration of diabetes.
      CONCLUSIONS: Insulin treatment in patients with type 2 diabetes mellitus affects
      the expression of inflammatory cytokines and subsequently modifies the thrombotic
      mechanisms in patients with coronary atherosclerosis, independently from the
      duration of diabetes and the extend of coronary artery disease.

PMID- 17551968
TI  - Bone formation following OP-1 implantation is improved by addition of autogenous
      bone marrow cells in a canine femur defect model.
AB  - Osteogenic Protein-1 (OP-1, BMP-7) acts locally on connective tissue progenitors
      (CTPs) to induce bone formation. The response to OP-1 and similar agents is
      potentially limited by the number of local CTPs. This study tested the hypothesis
      that supplementing local CTPs using autogenous bone marrow will enhance bone
      formation at an OP-1 implant. Four 1.0-cm diameter unicortical cylindrical
      defects in the left proximal femur were grafted in each of seven dogs. Radial
      ingrowth of new bone formation was assessed at 4 weeks using micro CT. The OP-1
      (3.5 mg rhOP-1 in 1 g bovine collagen I matrix) was implanted in each site
      combined with either clotted blood or aspirated bone marrow (BM). Bone formation
      was increased in the group augmented with transplanted marrow. These data suggest
      that increasing the local population of cells and CTPs using aspirated bone
      marrow can enhance the performance of OP-1, but may not eliminate the effects of
      site variation on the response to OP-1 and similar agents. The canine multiple
      femoral defect model defined in this study is well suited to quantitatively
      evaluate strategies for augmenting bone repair using local cell targeting and
      cell transplantation strategies.

PMID- 17551969
TI  - Tip60 modulates PLAGL2-mediated transactivation by acetylation.
AB  - Pleiomorphic adenoma gene (PLAG) family proteins are oncogenes involved in
      various malignancies including lipoblastomas, hepatoblastomas, and acute myeloid
      leukemia. Overexpression of PLAGL2 induces cell transformation and proliferation,
      but little is known about how its activities are regulated. We previously showed
      that transcriptional activity of PLAGL2 is negatively regulated by sumoylation.
      Here we report that Tip60 modulates PLAGL2 functions through acetylation. Tip60
      associates with PLAGL2 through its zinc finger domain and acetylates PLAGL2. Wild
      type but not the histone acetyltransferase (HAT)-minus mutant form of Tip60
      enhances PLAGL2-mediated transactivation. In addition, coexpression of Tip60 and
      PLAGL2 completely abolishes the sumoylation of PLAGL2. Both Tip60 and DN-Ubc9
      increase transactivation activity of wild-type but not the sumoylation deficient
      form of PLAGL2 (K250, 269, 356R), indicating that Tip60 acetylates PLAGL2 and
      abolishes the sumoylation of PLAGL2 possibly through modification of the same
      lysine residues (K250, 269, 356) within PLAGL2. Tip60 effects vary between
      different PLAGL2 target gene promoters, suggesting that Tip60 is a novel promoter
      specific coactivator of PLAGL2. This is the first demonstration that Tip60 can
      function as a sumoylation inhibitor in part through its intrinsic
      acetyltransferase activity to regulate specific gene expression.

PMID- 17551970
TI  - Automated medical vigilance on the medical/surgical ward of an acute care
      hospital.

PMID- 17551971
TI  - The Jahn-Teller effect of the Cr(2+) ion in aqueous solution: Ab initio QM/MM
      molecular dynamics simulations.
AB  - The hydration structure of Cr(2+) has been studied using molecular dynamics (MD)
      simulations including three-body corrections and combined ab initio quantum
      mechanical/molecular mechanical (QM/MM) MD simulations at the Hartree-Fock level.
      The structural properties are determined in terms of radial distribution
      functions, coordination numbers, and several angle distributions. The mean
      residence time was evaluated for describing ligand exchange processes in the
      second hydration shell. The Jahn-Teller distorted octahedral [Cr(H(2)O)(6)](2+)
      complex was pronounced in the QM/MM MD simulation. The first-shell distances of
      Cr(2+) are in the range of 1.9-2.8 A, which are slightly larger than those
      observed in the cases of Cu(2+) and Ti(3+). No first-shell water exchange
      occurred during the simulation time of 35 ps. Several water-exchange processes
      were observed in the second hydration shell with a mean residence time of 7.3 ps.

PMID- 17551972
TI  - Regenerative medicine in orthopaedic surgery.
AB  - Regenerative medicine holds great promise for orthopaedic surgery. As surgeons
      continue to face challenges regarding the healing of diseased or injured
      musculoskeletal tissues, regenerative medicine aims to develop novel therapies
      that will replace, repair, or promote tissue regeneration. This review article
      will provide an overview of the different research areas involved in regenerative
      medicine, such as stem cells, bioinductive factors, and scaffolds. The potential
      use of stem cells for orthopaedic tissue engineering will be addressed by
      presenting the current progress with skeletal muscle-derived stem cells. As well,
      the development of a revascularized massive allograft will be described and will
      serve as a prototypic model of orthopaedic tissue engineering. Lastly, we will
      describe current approaches used to design cell instructive materials and how
      they can be used to promote and regulate the formation of bony tissue.

PMID- 17551973
TI  - Electric field convergence versus atomic basis sets in all-siliceous zeolites.
AB  - The electrostatic potential (EP) and electric field (EF) are calculated in the
      TON and CHA zeolites using periodic hybrid B3LYP, PBE, and PW91 functionals
      considering eight basis sets. Relative root mean square differences between the
      EP or EF values estimated between the different basis sets are evaluated in
      several domains available for adsorbate molecules in both zeolites. The EP is
      interpreted in terms of ionicity of the framework.

PMID- 17551974
TI  - Molecular mechanics parameters for the FapydG DNA lesion.
AB  - FapydG is a common oxidative DNA lesion involving opening of the imidazole ring.
      It shares the same precursor as 8-oxodG and can be excised by the same enzymes as
      8-oxodG. However, the loss of the aromatic imidazole in FapydG results in a
      reduction of the double bond character between C5 and N7, with an accompanying
      increase in conformational flexibility. Experimental characterization of FapydG
      is hampered by high reactivity, and thus it is desirable to investigate
      structural details through computer simulation. We show that the existing Amber
      force field parameters for FapydG do not reproduce X-ray structural data. We
      employed quantum mechanics energy profile calculations to derive new molecular
      mechanics parameters for the rotation of the dihedral angles in the eximidazole
      moiety. Using these parameters, all-atom simulations in explicit water reproduce
      the nonplanar conformation of cFapydG in the crystal structure of the complex
      with L. lactis glycosylase Fpg. We note that the nonplanar structure is
      stabilized by an acidic residue that is not present in most Fpg sequences.
      Simulations of the E-->S mutant, as present in E. coli, resulted in a more planar
      conformation, suggesting that the highly nonplanar form observed in the crystal
      structure may not have direct biological relevance for FapydG.

PMID- 17551975
TI  - PDGF-BB released in tendon repair using a novel delivery system promotes cell
      proliferation and collagen remodeling.
AB  - The purpose of this study was to promote fibroblast proliferation and collagen
      remodeling in flexor tendon repair through sustained delivery of platelet derived
      growth factor (PDGF-BB). The release kinetics of PDGF-BB from a novel fibrin
      matrix delivery system was initially evaluated in vitro. After the in vivo
      degradation rate of the fibrin matrix was determined using fluorescently tagged
      fibrin, PDGF-BB was delivered to the site of flexor tendon repair in vivo in a
      canine model. The effect of PDGF-BB on intrasynovial tendon healing was studied
      using histology-based assays (cell density, proliferation, and type I collagen
      expression) and by measuring total DNA levels and reducible collagen crosslink
      levels. The fibrin matrix delivery system provided sustained release of PDGF-BB
      in vitro at a rate modulated by the ratio of heparin to growth factor. In vivo,
      the fibrin matrix remained at the repair site for more than 10 days. Delivery of
      PDGF-BB led to a qualitative increase in cell density, cell proliferation, and
      type I collagen mRNA expression. PDGF-BB also led to statistically significant
      increases in total DNA (20% increase at 7 days, 18% increase at 14 days) and
      reducible collagen crosslinks (30% increase at 7 days). Sustained delivery of
      growth factors may be achieved using a novel fibrin-based delivery system. PDGF
      BB delivery increased cell proliferation and matrix remodeling and thus may
      accelerate flexor tendon healing.

PMID- 17551976
TI  - Ovarian expression of p53 and p21 apoptosis regulators in gamma-irradiated mice.
AB  - Ovarian follicular degeneration is accelerated by gamma-radiation. To investigate
      the precise radiation-induced cellular and molecular biological changes in the
      ovary, prepubertal mice were whole-body irradiated with 6.94 Gy, which is the 30%
      of the lethal dose of gamma-radiation using a (60)Co source. At 0, 3, 6, 12, and
      24 hr after irradiation, ovarian expression of p53 and p21 mRNA and protein were
      analyzed by reverse-transcription polymerase chain reaction and immunoblotting,
      respectively. Immunohistochemical localization of p53 and p21 antigens was also
      carried out. Immunoreactive p53 and p21 were expressed in the nuclei of granulosa
      cells, but were not detected on the theca. In control mouse ovaries, p21 was
      weakly expressed on granulosa but not on the theca cells. In gamma-irradiated
      mouse ovaries, however, immunoreactive p21 proteins were detected in the nuclei
      of follicular granulosa cells. After irradiation expression of p53 and p21 mRNA
      and protein was significantly increased compared to beta-actin. Taken together,
      these observations suggest that p53 and p21 are actively involved in gamma
      radiation-induced follicular degeneration in the prepubertal mouse ovary.

PMID- 17551977
TI  - Deficiency in recapitulation of stage-specific embryonic gene transcription in
      two-cell stage cloned mouse embryos.
AB  - One possible explanation to account for the ability to clone animals by somatic
      cell nuclear transfer is that the donor genome is reprogrammed by the oocyte to
      recapitulate a normal embryonic pattern of gene expression. Mouse embryos display
      transient transcriptional induction of a group of genes (TIGs) at the mid two
      cell stage, the first major transcriptional output of the embryonic genome,
      uniquely suited for evaluating whether the oocyte directs correct and efficient
      recapitulation of an embryo stage-specific gene expression program before any in
      vitro selection occurs. We analyzed the expression of eight TIGs in two-cell
      stage clones prepared with cumulus cell nuclei. One failed to be transcribed, and
      seven others were transcribed, but supported significantly reduced mRNA
      expression. The reduction ranged from 1.6- to 17-fold at the mid two-cell stage,
      and 1.5- to 13-fold for the late two-cell stage. Five genes were not expressed in
      the donor cells, and these displayed the most pronounced deficiencies in
      expression. Two genes were expressed in cumulus cell donors, and supported
      progressive accumulation of their mRNAs in clones during this period, albeit at
      reduced rates. One other gene expressed in cumulus cells was not activated in
      clones. Although a significant proportion of these genes is reactivated in two
      cell stage clones, this recapitulation is grossly imperfect, occurs at a
      substantially reduced level, and even fails entirely to occur for some genes.
      Thus, the oocyte is incapable of efficiently directing the recapitulation of
      early embryonic stage-specific gene expression.

PMID- 17551978
TI  - Phosphorylation of Bcl-xL after spinal cord injury.
AB  - Spinal cord injury (SCI)-induced functional impairment results from secondary
      apoptosis regulated in part by SCI-induced decreases in the antiapoptotic protein
      Bcl-x(L). We assessed the role that Bcl-x(L) subcellular rerouting and
      posttranslational phosphorylation play in Bcl-x(L) decreases in a contusion model
      of rat SCI. Immunohistochemical analysis showed the presence of Bcl-x(L) in
      neurons and oligodendrocytes, but not in astrocytes and microglia, whereas
      phosphorylated Bcl-x(L) (P-ser(62)-Bcl-x(L)) was present only in neurons. Western
      blot analyses showed Bcl-x(L) present in mitochondria, endoplasmic reticulum,
      nuclei, and cytosolic extracts, whereas P-ser(62)-Bcl-x(L) was restricted to
      organelles. During the first 24 hr after SCI, Bcl-x(L) levels decreased in all
      fractions but with a different time course, suggesting an independent regulation
      of Bcl-x(L) shuttling from the cytosol to each compartment after SCI. SCI did not
      affect P-ser(62)-Bcl-x(L) levels in organelles. However, P-ser(62)-Bcl-x(L),
      which was not detected in the cytosolic fraction of uninjured spinal cord,
      appeared in the cytosol as early as 15 min postcontusion, suggesting a role for
      phosphorylation in SCI-induced Bcl-x(L)-decreases. Using an in vitro model, we
      observed a correlation between levels of cytosolic phosphorylated Bcl-x(L) and
      neuronal apoptosis, supporting the hypothesis that Bcl-x(L) phosphorylation is
      proapoptotic. Activated microglia/macrophages robustly expressed Bcl-x(L) 7 days
      after SCI, and a subpopulation showing nuclear condensation also expressed P
      ser(62)-Bcl-x(L). Therefore, phosphorylation of Bcl-x(L) may have opposite
      effects in injured spinal cords: 1) it may decrease levels of the antiapoptotic
      Bcl-x(L) in neurons contributing to neuronal death, and 2) it may promote
      apoptosis in activated microglia/macrophages, thus curtailing the inflammatory
      cascades associated with SCI.

PMID- 17551979
TI  - Temporal and spatial profiles of cell loss after spinal cord injury: Reduction by
      a metalloporphyrin.
AB  - This study presents quantitative temporal and spatial profiles of neuronal loss
      and apoptosis following a contusion spinal cord injury (50 g . cm). The profiles
      were evaluated by counting the cresol violet-stained surviving cells and the
      total number of TUNEL-positive cells and of TUNEL-positive neurons in sections 0-
      4 mm from the epicenter and 1, 6, 12, 24, 48, and 72 hr and 1 week postinjury. We
      demonstrated that neurons continue to disappear over 1 week postinjury and that
      neuronal loss shifts to areas longer distances from the epicenter over time.
      TUNEL-positive cells in both gray and white matter appeared after 6 hr, gradually
      increased to a peak level after 48 hr, and declined by 72 hr postinjury. TUNEL
      positive neurons peaked earlier and were present for 1 week, although the total
      number of neurons was reduced significantly by the end of the week. The neuronal
      loss and apoptosis were partially prevented by a metalloporphyrin [Mn(III)
      tetrakis (4-benzoic acid) porphyrin (MnTBAP)]. We demonstrated that MnTBAP (10
      and 50 mg/kg, given intraperitoneally) significantly reduced neuronal death in
      the sections 1-2.5 mm rostral and 1 mm caudal from the epicenter compared with
      that in the vehicle-treated group, suggesting MnTBAP is more effective in the
      sections rostral than in those caudal to the epicenter. MnTBAP (10 mg/kg)
      significantly reduced the number of TUNEL-positive neurons in the sections 1 mm
      caudal from the epicenter. Our profiles provide a database for pharmacological
      intervention, and our results on MnTBAP treatment support an important role for
      antioxidant therapy in spinal cord injury.

PMID- 17551980
TI  - Acute ammonia neurotoxicity in vivo involves increase in cytoplasmic protein P53
      without alterations in other markers of apoptosis.
AB  - Acute intoxication with large ammonia doses leads to activation of NMDA receptors
      in the brain, resulting in oxidative stress and disturbance of mitochondrial
      function. Altered mitochondrial function is a crucial step in some mechanisms of
      cellular apoptosis. This study assesses whether ammonia intoxication in vivo
      leads to induction of apoptotic markers such as permeability transition pore
      (PTP) formation, caspase-3, and caspase-9 activation, changes in p53 protein, or
      cytochrome c release. Acute ammonia intoxication did not affect caspase-9 or
      caspase-3 activities. The mitochondrial membrane potential also remained
      unaltered in non-synaptic brain mitochondria after injection of ammonia,
      indicating that ammonia did not induce PTP formation in brain in vivo. The
      nuclear level of p53 did not change, whereas its cytoplasmic level increased
      approximately two-fold. In agreement with the theory that translocation of the
      p53 from cytosol to nuclei is an essential step for induction of apoptosis we did
      not find apoptotic nuclei in brain of rats injected with ammonia. This supports
      the idea that ammonia neurotoxicity does not involve apoptosis and points to
      impaired p53 transfer from cytoplasm to nuclei as a possible preventer of
      apoptosis. We did not find any release of cytochrome c from mitochondria to
      cytosol after ammonia injection. Cytochrome c content was significantly reduced
      (30%) in brain mitochondria from rats injected with ammonia. This decrease may
      contribute to the reduced state 3 respiration, decreased respiratory control
      index, and disturbances in the mitochondrial electron transport chain in brain
      mitochondria from rats injected with ammonia.

PMID- 17551981
TI  - Measurement of brain microglial proliferation rates in vivo in response to
      neuroinflammatory stimuli: application to drug discovery.
AB  - Microglial activation is emerging as an important etiologic factor and
      therapeutic target in neurodegenerative and neuroinflammatory diseases.
      Techniques have been lacking, however, for measuring the different components of
      microglial activation independently in vivo. We describe a method for measuring
      microglial proliferation rates in vivo using heavy water (2H2O) labeling, and its
      application in screening for drugs that suppress neuro-inflammation. Brain
      microglia were isolated by flow cytometry as F4/80+, CD11b+, CD45(low) cells, and
      2H enrichment in DNA was analyzed by gas chromatography/mass spectrometry. Basal
      proliferation rate was approximately 1%/week and systemic administration of
      bacterial lipopolysaccharide (LPS) markedly increased this rate in a dose
      dependent manner. Induction of experimental autoimmune encephalomyelitis (EAE) in
      C57BL/6 mice by MOG(35-55) peptide stimulated proliferation of CD45(low)
      microglia, which could be distinguished from the proliferation of CD45(high)
      infiltrating monocytes. Minocycline (45 mg/kg/day, i.p.) inhibited resident
      microglial proliferation in both the LPS and EAE models. Thirteen drugs were then
      screened for their ability to inhibit LPS-stimulated microglia proliferation.
      Female C57BL/6 mice were given LPS (1 mg/kg), and concomitant drug treatment
      while receiving 2H2O label for 7 days. Among the drugs screened, treatment with
      isotretinoin dose-dependently reduced LPS-induced microglial proliferation,
      representing an action of retinoids unknown previously. Follow-up studies in the
      EAE model confirmed that isotretinoin not only inhibited proliferation of
      microglia but also delayed the onset of clinical symptoms. In conclusion, 2H2O
      labeling represents a relatively high-throughput, quantitative, and highly
      reproducible technique for measuring microglial proliferation, and is useful for
      screening and discovering novel anti-neuroinflammatory drugs.

PMID- 17551982
TI  - Signaling through C5aR is not involved in basal neurogenesis.
AB  - The complement system, an important part of the innate immune system, provides
      protection against invading pathogens, in part through its proinflammatory
      activities. Although most complement proteins are synthesized locally in the
      brain and the relevant complement receptors are expressed on resident brain
      cells, little is known about brain-specific role(s) of the complement system. C3a
      and C5a, complement-derived peptides with anaphylatoxic properties, have been
      implicated in noninflammatory functions, such as tissue regeneration and
      neuroprotection. Recently, we have shown that signaling through C3a receptor
      (C3aR) is involved in the regulation of neurogenesis. In the present study, we
      assessed basal neurogenesis in mice lacking C5a receptor (C5aR(-/-)) and mice
      expressing C3a and C5a, respectively in the CNS under the control of glial
      fibrillary acidic protein (GFAP) promoter (C3a/GFAP and C5a/GFAP, respectively)
      and thus without the requirement for complement activation. We did not observe
      any difference among C5aR(-/-), C3a/GFAP and C5a/GFAP mice and their respective
      controls in the number of newly formed neuroblasts and newly formed neurons in
      the subventricular zone (SVZ) of lateral ventricles and hippocampal dentate
      gyrus, the two neurogenic niches in the adult brain, or the olfactory bulb, the
      final destination of new neurons formed in the SVZ. Our results indicate that
      signaling through C5aR is not involved in basal neurogenesis in adult mice and
      that basal neurogenesis in adult C3a/GFAP and C5a/GFAP mice is not altered.

PMID- 17551985
TI  - Sickle cell disease caused by Hb S/Quebec-CHORI: treatment with hydroxyurea and
      response.
AB  - Sickle hemoglobin (Hb S;betaGlu 6 Val) is due to an A>T transversion in codon 6
      of the beta-globin gene. Other variant hemoglobins mimic Hb A, S, or C on newborn
      screening and clinical laboratory diagnostic tools, thus making their correct
      identification potentially difficult. Sickling disorders can result in
      individuals who are compound heterozygous for beta-globin mutations (e.g., Hb SC,
      HbSO(Arab)). The authors report a second case of HbS/Quebec-CHORI, a severe
      compound heterozygous sickling disorder and their experience managing this
      patient with hydroxyurea.

PMID- 17551986
TI  - Identification of synaptic activity-dependent genes by exposure of cultured
      cortical neurons to tetrodotoxin followed by its withdrawal.
AB  - Activity-dependent gene expression is one of the key mechanisms of synaptic
      plasticity that form the basis of higher order functions such as learning and
      memory. In the present study, we surveyed for activity-dependent genes by
      analyzing gene expression changes accompanying reversible inhibition of synaptic
      activity by tetrodotoxin (TTX) using two types of DNA microarrays; our focused
      oligo DNA microarray "Synaptoarray" and the commercially available high-density
      array. Cerebral cortical cells from E18 rat embryos were cultured for 14 days to
      ensure synaptogenesis, then treated with 1 muM TTX for 48 hr without detectable
      effect on cell viability. Synaptic density estimated by the amount of Synapsin I
      and Synaptotagmin I was decreased 21-24% by TTX treatment, but recovered to the
      control level 48 hr after TTX withdrawal. Comparison of gene expression profiles
      by competitive hybridization of fluorescently labeled cRNA from TTX-treated and
      control cells showed an overall downregulation of the genes on the Synaptoarray
      by TTX-treatment with different recovery rates after TTX withdrawal. With 16
      representative genes, microarray data were validated by real-time PCR analysis.
      Genes most severely downregulated by TTX and upregulated above the control level
      at 5 hr after TTX withdrawal were munc13-1 (involved in docking and priming of
      synaptic vesicles) and Shank2 (involved in the postsynaptic scaffold). In
      addition, comprehensive screening at 5 hr after TTX withdrawal using high density
      arrays resulted in additional identification of Rgs2, a regulator of trimeric G
      protein signaling, as an activity-dependent gene. These three genes are thus
      likely to be key factors in the regulation of synaptic plasticity. (c) 2007 Wiley
      Liss, Inc.

PMID- 17551984
TI  - Coherent anti-Stokes Raman scattering imaging of myelin degradation reveals a
      calcium-dependent pathway in lyso-PtdCho-induced demyelination.
AB  - Coherent anti-Stokes Raman scattering (CARS) microscopy, which allows vibrational
      imaging of myelin sheath in its natural state, was applied to characterize
      lysophosphatidylcholine (lyso-PtdCho)-induced myelin degradation in tissues and
      in vivo. After the injection of lyso-PtdCho into ex vivo spinal tissues or in
      vivo mouse sciatic nerves, myelin swelling characterized by the decrease of CARS
      intensity and loss of excitation polarization dependence was extensively
      observed. The swelling corresponds to myelin vesiculation and splitting observed
      by electron microscopy. The demyelination dynamics were quantified by the
      increase of g ratio measured from the CARS images. Treating spinal tissues with
      Ca2+ ionophore A23187 resulted in the same kind of myelin degradation as lyso
      PtdCho. Moreover, the demyelination lesion size was significantly reduced upon
      preincubation of the spinal tissue with Ca2+ free Krebs' solution or a cytosolic
      phospholipase A2 (cPLA(2)) inhibitor or a calpain inhibitor. In accordance with
      the imaging results, removal of Ca2+ or addition of cPLA(2) inhibitor or calpain
      inhibitor in the Krebs' solution remarkably increased the mean compound action
      potential amplitude in lyso-PtdCho treated spinal tissues. Our results suggest
      that lyso-PtdCho induces myelin degradation via Ca(2+) influx into myelin and
      subsequent activation of cPLA(2) and calpain, which break down the myelin lipids
      and proteins. The current work also shows that CARS microscopy is a potentially
      powerful tool for the study of demyelination.

PMID- 17551987
TI  - Changes in the connections of the main olfactory bulb after mitral cell selective
      neurodegeneration.
AB  - The connections of the main olfactory bulb (OB) of the mouse were studied with
      iontophoretic injections of biotinylated dextran amine. To sort efferences from
      mitral cells and tufted cells, the Purkinje cell degeneration (PCD) mouse was
      used. This mutant animal undergoes a specific neurodegeneration of mitral cells,
      whereas tufted cells do not degenerate. The unilateral tracer injections used
      were small and confined largely to the OB of both PCD and control mice at P120.
      Seven days after tracer injection, the efferences from the OB and the centrifugal
      afferences from secondary olfactory structures to it were studied. Although there
      is a large overlap of their target fields, mitral cell axons innervated more
      caudal regions of the olfactory cortex than tufted cell axons, thus providing
      definitive evidence of the differential projections of olfactory output neurons.
      Additionally, an important increase in retrogradely-labeled neurons was detected
      in the ipsilateral anterior olfactory nucleus of the mutant animals. This was not
      observed in any other secondary olfactory structure, suggesting a strengthening
      of the centrifugal input to the OB from that central area after mitral cell loss.
      Moreover, we recorded a complete loss of bilaterality in the olfactory
      connections of the PCD mice due to degeneration of the anterior commissure. These
      results point to an important reorganization of this essential olfactory circuit
      between the anterior olfactory nucleus and the OB, and hint at a transsynaptic
      level of plasticity not considered previously in literature.

PMID- 17551988
TI  - Linking physiology and transcriptional profiles by quantitative predictive
      models.
AB  - A methodology for the construction of quantitative, predictive models of
      physiology from transcriptional profiles is presented. The method utilizes
      partial least squares (PLS) regression properly modified to allow gene pre
      selection based on their signal-to-noise ratio (SNR). The final set of genes is
      obtained from a consensus ranking of genes across several thousand trials, each
      carried out with a different set of training samples. The method was tested with
      transcriptional data from a large-scale microarray study profiling the effects of
      high-fat diet on the diet-induced obese mouse model C57BL/6J, and the obese
      resistant A/J mouse model. Quantitative predictive models were constructed for
      the age of the C57BL/6J mice and the A/J mice, and for the insulin and leptin
      levels of the C57Bl/6J mice based on transcriptional data of liver obtained over
      a 12-week period. Similarly, models for the growth rate of yeast mutants, and the
      age of Drosophila samples were developed from literature data. Specifically, it
      is demonstrated that highly predictive models can be constructed with current
      levels of precision in DNA microarray measurements provided the variation in the
      physiological measurements is controlled. Genes identified by this method are
      important for their ability to collectively predict phenotype. The method can be
      expanded to include various types of physiological or cellular data, thus
      providing an integrative framework for the construction of predictive models.

PMID- 17551989
TI  - Coronary heart disease outcomes in patients receiving antidiabetic agents.
AB  - BACKGROUND: There is conflicting evidence on the reduction of cardiovascular risk
      in diabetic patients treated with oral antidiabetic agents. OBJECTIVES: To
      compare the risk of myocardial infarction (MI) and coronary revascularization
      (CR) in type 2 diabetic patients treated with rosiglitazone, metformin, or
      sulfonylurea. METHODS: Using data from a large US insurer, we created propensity
      matched cohorts. We identified hospitalizations for MI or CR. We calculated
      incidence rates and 95% confidence intervals for the outcomes and estimated risks
      from Cox proportional hazards models. RESULTS: We identified 26,931 initiators of
      monotherapy, 4,086 initiators of dual-therapy, and 2,346 initiators of
      combination with insulin therapy. There was no difference between the risk of the
      composite outcome with rosiglitazone monotherapy compared to metformin
      monotherapy (HR 1.07, 95% CI: 0.85, 1.34), and similarly with rosiglitazone
      monotherapy compared to sulfonylurea monotherapy (HR 0.82, 95% CI: 0.67, 1.02).
      There was no difference in the risk of outcome with rosiglitazone in combination
      with insulin therapy compared to other oral antidiabetic agents in combination
      with insulin (HR 0.88, 95% CI: 0.59, 1.32). Overall, there was little difference
      in the risk of the composite outcome or of the individual outcomes of MI and CR
      comparing rosiglitazone therapies to non-rosiglitazone therapies (HR for
      composite outcome 0.93, 95% CI: 0.80, 1.10). CONCLUSIONS: The results from the
      monotherapy and the dual-therapy comparisons, though not individually
      significant, are consistent in suggesting that the risk of cardiovascular outcome
      events in patients using rosiglitazone may lie between the risks associated with
      sulfonylureas (higher incidence) and metformin (lower incidence).

PMID- 17551990
TI  - Analyses of pesticide residues in fruit-based baby food by liquid
      chromatography/electrospray ionization time-of-flight mass spectrometry.
AB  - A liquid chromatography/electrospray ionization time-of-flight mass spectrometry
      (LC/ESI-TOFMS) method has been developed for the determination of 12 pesticides
      (namely, carbendazim, thiabendazole, imazalil, tridemorph, triadimefon,
      bitertanol, prochloraz, flutriafol, myclobutanil, iprodione, diphenylamine and
      procymidone) in fruit-based baby food (multi-fruit jars and juices intended for
      infant consumption). The developed method consists of a sample treatment step
      based on liquid-liquid extraction using acetonitrile, followed by a clean-up step
      based on dispersive solid-phase extraction (SPE) with a primary-secondary amine
      (PSA). Multi-fruit and apple juices were processed by a SPE procedure using Oasis
      HLB cartridges. Subsequent identification and quantitation was accomplished by
      LC/ESI-TOFMS analysis: the confirmation of the target pesticides was based on
      accurate mass measurements of selected ions (protonated molecules ([M+H]+) and
      fragment ions). Confirmation studies were accomplished at low concentration
      levels (10 microg kg-1) and accuracy errors lower than 2 ppm were obtained in
      most cases. Baby food extracts spiked at 10 microg kg-1 fortification level
      yielded average recoveries in the range 78-105% with relative standard deviations
      less than 10% for most of the analytes. Limits of detection (LODs) were between
      0.1 and 4 microg kg-1 depending on the pesticide studied. Finally, the proposed
      method was applied to a total of 33 baby food samples from Spain and the United
      Kingdom. Although imazalil, thiabendazole and carbendazim were detected in a high
      number--over 60%- of baby food samples, none of the samples tested were found to
      be above the 0.01 mg kg-1 EU standard.

PMID- 17551991
TI  - Enumeration of carbohydrate hydroxyl groups by silylation and matrix-assisted
      laser desorption/ionization time-of-flight mass spectrometry.
AB  - A method for enumerating hydroxyl groups in analytes is described and applied to
      various carbohydrates. The analytes were derivatized in solution by using
      trimethylsilylimidazole (TMSI) and the products were analyzed without
      chromatography by matrix-assisted laser desorption/ionization time-of-flight mass
      spectrometry (MALDI-TOF-MS). The mass spectra revealed consecutive product ion
      peaks that are separated by 72 m/z units. This 72 m/z unit separation is a result
      of displacement of a hydroxyl hydrogen atom by a trimethylsilyl group. The number
      of the observed ions was used to confirm the number of hydroxyl groups in each
      analyte. This method was utilized in the analysis of single and multi-component
      analytes.

PMID- 17551993
TI  - Synthesis and mass spectrometry of benzoxazoline, dimethyloxazoline and 4
      phenyloxazoline derivatives of polyunsaturated fatty acids.
AB  - Cyclic nitrogen moieties have proved to be of great value for the mass
      spectrometric location of double bonds in polyunsaturated fatty acids. However,
      their synthesis has traditionally required long reaction times and/or high
      temperatures. Recently, we introduced a one-pot, high-yield, mild and efficient
      method for the synthesis of various fatty acid amide derivatives. We have now
      extended this procedure to include the synthesis of benzoxazoline,
      dimethyloxazoline and 4-phenyloxazoline analogs of a series of fatty acids
      containing 18 to 22 carbon atoms and 0 to 6 double bonds. A comparison of the
      mass spectral properties of the three derivatives of these saturated and
      unsaturated fatty acids is described.

PMID- 17551992
TI  - Antidepressant use and off-label prescribing in children and adolescents in Dutch
      general practice (2001-2005).
AB  - PURPOSE: To study the use of antidepressants in children and adolescents in Dutch
      general practice in 2001 and 2005 and to determine off-label prescribing.
      METHODS: Data were obtained from the Netherlands Information Network of General
      Practice (LINH) that comprised 97 practices in 2001 and 73 practices in 2005.
      General practitioners (GPs) recorded prescriptions with their indication in the
      medical records of the patients during one calendar year. We selected boys and
      girls aged 0-17 years (n = 83 442 in 2001; n = 62 969 in 2005) and identified
      those who got prescribed antidepressants (N06A). Prevalence of use, indications
      and percentage of off-label prescriptions were compared between 2001 and 2005.
      RESULTS: The prevalence of selective serotonin reuptake inhibitor (SSRI) use
      decreased from 1.2 to 1.1 per 1000 children and adolescents between 2001 and
      2005. The use of tricyclic antidepressants (TCAs) and other antidepressants also
      decreased (0.8 to 0.7 and 0.3 to 0.2, respectively). TCAs were often prescribed
      for nocturnal enuresis, but in patients aged 12-17 years hyperactivity was the
      leading indication in both years. GPs continued to prescribe SSRIs for depression
      (about half of the prescriptions) after the safety warnings, while venlafaxine
      prescribed for depression decreased in favour of anxiety. Off-label prescribing
      of SSRIs increased from 16.7% to 34.4% and that of venlafaxine from 22.2% to
      58.3%. All SSRI and venlafaxine prescriptions were unlicensed for age.
      CONCLUSIONS: The decreased use of SSRIs and venlafaxine suggests an impact of the
      safety warnings. A point of concern is the enlarged off-label prescribing and
      insight in the underlying reasons and its appropriateness is needed.

PMID- 17551994
TI  - Utilisation review of clopidogrel: are they used under the FDA-approved
      indications?
AB  - BACKGROUND: Clopidogrel has shown benefit in patients with increased risk of
      cardiovascular diseases. Due to its high acquisition cost and its increased use,
      this study was conducted to review the use of clopidogrel based on the Food and
      Drug Administration (FDA)-approved indications and the ST-segment elevation
      myocardial infarction (STEMI). METHOD: This was a cross-sectional study conducted
      at a tertiary-care, university-affiliated hospital in the Northern part of
      Thailand. Medical records of patients receiving clopidogrel during January 2005
      to February 2006 were reviewed. Baseline characteristics of patients along with
      specific information regarding the use of clopidogrel were collected. Data were
      analysed using descriptive statistics. RESULT: A total of 191 patients were
      included in this utilisation review (95 and 96 were inpatient and outpatient,
      respectively). The use of clopidogrel was deemed appropriate in 82.7% of cases
      including 72.2% for FDA-approved indications and 10.5% for STEMI.
      Clopidogrel/aspirin combination was indicated in 93 patients; however, 22
      patients received clopidogrel monotherapy. On the contrary, 10 patients received
      clopidogrel/aspirin combination when only clopidogrel monotherapy was indicated.
      Moreover, 60% of patients who received clopidogrel monotherapy had no history of
      aspirin intolerance or recurrent events while on aspirin therapy. CONCLUSION: The
      results showed that the majority of clopidogrel use was deemed appropriate based
      on FDA-approved indications and for medically justified indication. However, a
      significant number of patients received clopidogrel instead of aspirin while no
      aspirin intolerance was documented. Therefore, efforts should be made to promote
      the appropriate use of this agent to improve patient outcomes.

PMID- 17551995
TI  - The impact of pharmaceuticals on the decline of cardiovascular mortality in
      Germany.
AB  - PURPOSE: The effect of innovative medicines and surgical interventions on the
      decline of (cardiovascular) mortality is often called into question. The increase
      in general economic prosperity is often seen as the main reason for the
      continuous increase in life expectancy. The purpose of this study is to
      investigate the extent to which mortality from cardiovascular diseases has been
      affected by pharmaceuticals and other medical interventions over the last 30
      years in Germany. METHODS: Main outcome measures were the time series of direct
      method death rates (DMDR) of cardiovascular and non-cardiovascular mortalities.
      To control for socioeconomic and secular trends the difference between both time
      series was calculated. The impact of interventions on mortality was analysed by
      developing two linear regression models: The onset model analyses whether the
      introduction of interventions influences mortality or not. The consumption model
      estimates the quantitative impact of interventions in two phases. RESULTS:
      Cardiovascular mortality as a percentage of total mortality fell from 40 to 38%
      over the study period. All investigated interventions had statistically
      significant effects on the decline of cardiovascular diseases, which is expressed
      by the standardised regression coefficient: onset model: preventive behaviour
      index (PBI) -8.3, angioplasty/CABG -0.6, antithrombotic agents -1.5, diuretics 
      0.9, beta-blockers -1.0, calcium channel blockers -0.8 and ACE inhibitors -1.1
      (all interventions p < 0.01); consumption model: innovative drugs phase I -7.5 (p
      = 0.017), innovative drugs phase II -6.9 (p < 0.01), PBI -13.1 (p < 0.01) and
      angioplasty/CABG -9.9 (p < 0.01). CONCLUSIONS: All innovative drug classes and
      surgical interventions had a positive effect on the decline of cardiovascular
      mortality.

PMID- 17551996
TI  - The European sertindole safety and exposure survey: a follow-up study of 8600
      patients.
AB  - BACKGROUND: A regulatory signal suggested that sertindole was associated with a
      10-fold increased risk of death. This observational study aimed to identify
      deaths and their causes in patients treated with sertindole. METHODS: Sertindole
      treated patients in Germany, Austria, Belgium, Hungary, The Netherlands and the
      United Kingdom were identified and their vital status ascertained. Eventual cause
      of death and patient and treatment characteristics were ascertained. A nested
      case-control study compared on-treatment cardiac or unexplained deaths with
      randomly selected survivors matched on age and gender for potential risk factors.
      RESULTS: Eight thousand six hundred eight patients were identified as having
      initiated treatment with sertindole, for a total 3819 person-years exposure.
      Thirty-five had died since (all-cause mortality rate 0.92 per 100 person-years
      exposed). Of these, 15 (43%) had been previously reported to the regulatory
      authorities. Eight deaths were suicides, of which 2 (25%) had been previously
      reported; 11 were cardiac deaths, of which 8 (73%) had been reported. On average,
      patients who died because of cardiac disorders were older, and patients who
      committed suicide were younger than the other patients who died. The nested case
      control study revealed that patients receiving sertindole were at a higher risk
      of premature cardiac or unexplained death if they had hypertension or other
      cardiovascular disorders associated with diabetes or metabolic disorder.
      CONCLUSION: Overall and cardiovascular death rates were similar or lower than
      those observed in premarketing clinical trials. There was a very high reporting
      rate of all-cause and cardiovascular deaths that could have contributed to the
      regulatory alert.

PMID- 17551997
TI  - Rapid structural determination of new trace cassaine-type diterpenoid amides in
      fractions from Erythrophleum fordii by liquid chromatography-diode-array
      detection/electrospray ionization tandem mass spectrometry and liquid
      chromatography/nuclear magnetic resonance.
AB  - Electrospray ionization multi-stage tandem mass spectrometry (ESI-MSn), and
      combination with HPLC (HPLC/ESI-MSn), have been extensively applied to on-line
      analysis of natural products. Hyphenation of liquid chromatography to nuclear
      magnetic resonance spectroscopy (HPLC/NMR) has been developed in the last decade,
      which is utilized for the analysis of metabolites and drug impurities. In the
      study reported here, the fragmentation behaviors of eight cassaine-type
      diterpenoid amides from Erythrophleum fordii were investigated by ESI-MSn. The
      fragmentation rules and NMR spectral characteristics are summarized, and the
      relationship among the rules, characteristics and the structures is described.
      According to the fragmentation rules and NMR spectral characteristics, seven
      trace constituents and two formerly obtained compounds of cassaine-type
      diterpenoid amides in the fractions from E. fordii were structurally
      characterized on the basis of HPLC/HRMS, HPLC-DAD/ESI-MSn, HPLC/1H NMR and
      HPLC/1H-1H COSY rapidly. Among them, constituents 1-5 are new compounds, and 6
      and 7 are reported from E. fordii for the first time. The aim is to develop an
      effective analytical method for structural identification of new trace natural
      products in plants.

PMID- 17551998
TI  - Magnifying chromoscopy, a novel and useful technique for colonoscopy in
      ulcerative colitis.
AB  - Ulcerative colitis (UC) is a chronic inflammatory bowel disorder characterized by
      exacerbations and remissions. The degree of inflammation as assessed by
      conventional colonoscopy is a reliable parameter of disease activity. However,
      even when conventional colonoscopy suggests remission and normal mucosal
      findings, microscopic abnormalities may persist, and relapse may occur later.
      Patients with long-standing, extensive ulcerative colitis have an increased risk
      of developing colorectal cancer. Ulcerative colitis-associated colorectal cancer
      is characterized by an early age at onset, poorly differentiated tumor cells,
      mucinous carcinoma, and multiple lesions. Early detection of dysplasia and
      colitic cancer is thus a prerequisite for survival. A relatively new method,
      magnifying chromoscopy, is thought to be useful for the early detection and
      diagnosis of dysplasia and colitic cancer, as well as the prediction of relapse.

PMID- 17551999
TI  - Magnetic resonance cholangiopancreatography: a useful tool in the evaluation of
      pancreatic and biliary disorders.
AB  - Magnetic resonance cholangiopancreatography (MRCP) is being used with increasing
      frequency as a noninvasive alternative to diagnostic retrograde
      cholangiopancreatography (ERCP). The aim of this pictorial review is to
      demonstrate the usefulness of MRCP in the evaluation of pancreatic and biliary
      system disorders. Because the recently developed techniques allows improved
      spatial resolution and permits imaging of the entire pancreaticobiliary tract
      during a single breath hold, MRCP is of proven utility in a variety of pancreatic
      and biliary disorders. It uses MR imaging to visualize fluid in the biliary and
      pancreatic ducts as high signal intensity on T2 weighted sequences and is the
      newest modality for pancreatic and biliary duct imaging. Herein, we present the
      clinical applications of MRCP in a variety of pancreaticobiliary system disorders
      and conclude that it is an important diagnostic tool in terms of imaging of the
      pancreaticobiliary ductal system.

PMID- 17552000
TI  - Portal hypertension due to portal venous thrombosis: etiology, clinical outcomes.
AB  - The thrombophilia in adult life has major implications in the hepatic vessels.
      The resulting portal vein thrombosis has various outcomes and complications.
      Esophageal varices, portal gastropathy, ascites, severe hypersplenism and liver
      failure needing liver transplantation are known well. The newly formed collateral
      venous circulation showing itself as pseudocholangicarcinoma sign and its
      possible clinical reflection as cholestasis are also known from a long time. The
      management strategies for these complications of portal vein thrombosis are not
      different from their counterpart which is cirrhotic portal hypertension, but the
      prognosis is unquestionably better in former cases. In this review we present and
      discuss the portal vein thrombosis, etiology and the resulting clinical pictures.
      There are controversial issues in nomenclature, management (including
      anticoagulation problems), follow up strategies and liver transplantation. In the
      light of the current knowledge, we discuss some controversial issues in
      literature and present our experience and our proposals about this group of
      patients.

PMID- 17552001
TI  - Glycogen storage diseases: new perspectives.
AB  - Glycogen storage diseases (GSD) are inherited metabolic disorders of glycogen
      metabolism. Different hormones, including insulin, glucagon, and cortisol
      regulate the relationship of glycolysis, gluconeogenesis and glycogen synthesis.
      The overall GSD incidence is estimated 1 case per 20000-43000 live births. There
      are over 12 types and they are classified based on the enzyme deficiency and the
      affected tissue. Disorders of glycogen degradation may affect primarily the
      liver, the muscle, or both. Type Ia involves the liver, kidney and intestine (and
      Ib also leukocytes), and the clinical manifestations are hepatomegaly, failure to
      thrive, hypoglycemia, hyperlactatemia, hyperuricemia and hyperlipidemia. Type
      IIIa involves both the liver and muscle, and IIIb solely the liver. The liver
      symptoms generally improve with age. Type IV usually presents in the first year
      of life, with hepatomegaly and growth retardation. The disease in general is
      progressive to cirrhosis. Type VI and IX are a heterogeneous group of diseases
      caused by a deficiency of the liver phosphorylase and phosphorylase kinase
      system. There is no hyperuricemia or hyperlactatemia. Type XI is characterized by
      hepatic glycogenosis and renal Fanconi syndrome. Type II is a prototype of inborn
      lysosomal storage diseases and involves many organs but primarily the muscle.
      Types V and VII involve only the muscle.

PMID- 17552002
TI  - Future prospectives for the management of chronic hepatitis B.
AB  - Chronic hepatitis B virus infection affects about 400 million people around the
      globe and causes approximately a million deaths a year. Since the discovery of
      interferon-alpha as a therapeutic option the treatment of hepatitis B has evolved
      fast and management has become increasingly complicated. The amount of viral
      replication reflected in the viral load (HBV-DNA) plays an important role in the
      development of cirrhosis and hepatocellular carcinoma. The current treatment
      modalities for chronic hepatitis B are immunomodulatory (interferons) and
      antiviral suppressants (nucleoside and nucleotide analogues) all with their own
      advantages and limitations. An overview of the treatment efficacy for both
      immunomodulatory as antiviral compounds is provided in order to provide the
      clinician insight into the factors influencing treatment outcome. With nucleoside
      or nucleotide analogues suppression of viral replication by 5-7 log(10) is
      feasible, but not all patients respond to therapy. Known factors influencing
      treatment outcome are viral load, ALT levels and compliance. Many other factors
      which might influence treatment are scarcely investigated. Identifying the
      factors associated with response might result in stopping rules, so treatment
      could be adapted in an early stage to provide adequate treatment and avoid the
      development of resistance. The efficacy of compounds for the treatment of mutant
      virus and the cross-resistance is largely unknown. However, genotypic and
      phenotypic testing as well as small clinical trials provided some data on
      efficacy in this population. Discontinuation of nucleoside or nucleotide
      analogues frequently results in viral relapse; however, some patients have a
      sustained response. Data on the risk factors for relapse are necessary in order
      to determine when treatment can be discontinued safely. IN CONCLUSION: chronic
      hepatitis B has become a treatable disease; however, much research is needed to
      tailor therapy to an individual patient, to predict the sustainability of
      response and determine the best treatment for those failing treatment.

PMID- 17552003
TI  - Promoter hypermethylation of CDH1, FHIT, MTAP and PLAGL1 in gastric
      adenocarcinoma in individuals from Northern Brazil.
AB  - AIM: To evaluate the methylation status of CDH1, FHIT, MTAP and PLAGL1 promoters
      and the association of these findings with clinico-pathological characteristics.
      METHODS: Methylation-specific PCR (MSP) assay was performed in 13 nonneoplastic
      gastric adenocarcinoma, 30 intestinal-type gastric adenocarcinoma and 35 diffuse
      type gastric adenocarcinoma samples from individuals in Northern Brazil.
      Statistical analyses were performed using the chi-square or Fisher's exact test
      to assess associations between methylation status and clinico-pathological
      characteristics. RESULTS: Hypermethylation frequencies of CDH1, FHIT, MTAP and
      PLAGL1 promoter were 98.7%, 53.9%, 23.1% and 29.5%, respectively.
      Hypermethylation of three or four genes revealed a significant association with
      diffuse-type gastric cancer compared with nonneoplastic cancer. A higher
      hypermethylation frequency was significantly associated with H pylori infection
      in gastric cancers, especially with diffuse-type. Cancer samples without lymph
      node metastasis showed a higher FHIT hypermethylation frequency. MTAP
      hypermethylation was associated with H pylori in gastric cancer samples, as well
      as with diffuse-type compared with intestinal-type. In diffuse-type, MTAP
      hypermethylation was associated with female gender. CONCLUSION: Our findings show
      differential gene methylation in tumoral tissue, which allows us to conclude that
      hypermethylation is associated with gastric carcinogenesis. MTAP promoter
      hypermethylation can be characterized as a marker of diffuse-type gastric cancer,
      especially in women and may help in diagnosis, prognosis and therapies. The H
      pylori infectious agent was present in 44.9% of the samples. This infection may
      be correlated with the carcinogenic process through the gene promoter
      hypermethylation, especially the MTAP promoter in diffuse-type. A higher H pylori
      infection in diffuse-type may be due to greater genetic predisposition.

PMID- 17552004
TI  - A preliminary study of neck-stomach syndrome.
AB  - AIM: To determine the expression of c-Fos, caspase-3 and interleukin-1beta (IL
      1beta) in the cervical cord and stomach of rats with cervical spondylosis, to
      analyze their relationship, and to offer an explanation of one possible cause for
      functional dyspepsia (FD) and irritable bowel syndrome (IBS) caused by cervical
      spondylosis. METHODS: The cervical spondylosis model in rats was established by
      destroying the stability of cervical posterior column. The cord segments C4-6 and
      gastric antrum were collected 3 mo and 5 mo after the operation. Rats with the
      sham operation were used as controls. The expressions of c-Fos, caspase-3 and IL
      1beta in the cervical cord and gastric antrum were determined by
      immunohistochemistry and/or Western blot. RESULTS: Immunohistochemical staining
      showed a few c-Fos, caspase-3 and IL-1beta-positive cells in the cervical cord
      and antrum in the control. There was a significant increase in c-Fos, caspase-3
      and IL-1beta expression in model groups compared to the control groups at 3 mo
      and 5 mo after operation. More importantly, there was a significant (P < 0.05)
      increase in c-Fos, caspase-3 and IL-1beta expression in the model group rats at 3
      mo compared to those at 5 mo after the operation (c-Fos: 11.20 +/- 2.26 vs 27.68
      +/- 4.36 in the cervical cord, 11.3 +/- 2.3 vs 29.3 +/- 4.6 in the gastric
      antrum; caspase-3: 33.83 +/- 3.71 vs 36.32 +/- 4.01 in the cervical cord, 13.23
      +/- 3.21 vs 26.32 +/- 4.01 in the gastric antrum; IL-1beta: 42.06 +/- 2.95 vs
      45.91 +/- 3.98 in the cervical cord, 26.56 +/- 2.65 vs 32.01 +/- 2.98 in the
      gastric antrum). Western blot analysis showed time-dependent changes of caspase-3
      and IL-1beta protein in the cervical cord and gastric antrum of rats with
      cervical spondylosis; there was no significant expression of caspase-3 and IL
      1beta protein in the control group at 3 mo and 5 mo after the sham operation,
      whereas there was a significant difference in caspase-3 and IL-1beta protein
      levels between the model group rats followed up for 3 mo and those for 5 mo (P <
      0.05). CONCLUSION: There is a significant association of c-Fos, caspase-3 and IL
      1beta expressions in the gastric antrum with that in the spinal cord in rats with
      cervical spondylosis, suggesting that the gastrointestinal function may be
      affected by cervical spondylosis.

PMID- 17552005
TI  - H pylori iceA alleles are disease-specific virulence factors.
AB  - AIM: To characterize and compare genotype profiles of H pylori strains isolated
      from patients with chronic gastritis and duodenal ulcer in western part of
      Turkey. METHODS: A total of 46 patients [30 chronic gastritis (CG) and 16
      duodenal ulcer (DU)] who had undergone endoscopy because of dyspeptic complaints
      were studied. The antral biopsy specimens were evaluated for the presence of H
      pylori by rapid urease test and culture, and the genotype profiles were
      determined by real-time PCR. RESULTS: The cagA gene was observed in 43 (93.5%)
      isolates. The vacA s1m2 genotype was the predominant subtype, found in 63.3% and
      68.7% of isolates in patients with CG and DU, respectively. Twenty (66.6%)
      isolates from patients with CG were iceA2 positive while the iceA1 was
      predominant in those with DU (68.8%). In terms of the association of the iceA
      alleles to other genes, both alleles were significantly associated with the cagA
      vacA s1m2 genotype. CONCLUSION: The prevalent circulating genotypes in CG and DU
      were cagA vacA s1m2 iceA2 and cagA vacA s1m2 iceA1 genotype, respectively. It was
      found that cagA vacA s1m2 genotype seems to be common virulence factors in both
      CG and DU while iceA alleles show specificity for gastroduodenal pathologies in
      this study.

PMID- 17552006
TI  - Long-term results of endosurgical and open surgical approach for Zenker
      diverticulum.
AB  - AIM: To assess the effectiveness of minimally invasive versus traditional open
      surgical approach in the treatment of Zenker diverticulum. METHODS: Between 1976
      and 2006, 297 patients underwent transoral stapling (n = 181) or stapled
      diverticulectomy and cricopharyngeal myotomy (n = 116). Subjective and objective
      evaluations of the outcome of the two procedures were made at 1 and 6 mo after
      operation, and then every year. Long-term follow-up data were available for a
      subgroup of patients at a minimum of 5 and 10 years. RESULTS: The operative time
      and hospital stay were markedly reduced in patients undergoing the endosurgical
      approach. Overall, 92% of patients undergoing the endosurgical approach and 94%
      of those undergoing the open approach were symptom-free or were significantly
      improved after a median follow-up of 27 and 48 mo, respectively. At a minimum
      follow-up of 5 and 10 years, most patients were asymptomatic after both
      procedures, except for those individuals undergoing an endosurgical procedure for
      a small diverticulum (< 3 cm). CONCLUSION: Both operations relieve the outflow
      obstruction at the pharyngoesophageal junction, indicating that cricopharyngeal
      myotomy has an important therapeutic role in this disease independent of the
      resection of the pouch and of the surgical approach. Diverticula smaller than 3
      cm represent a formal contraindication to the endosurgical approach because the
      common wall is too short to accommodate one cartridge of staples and to allow
      complete division of the sphincter.

PMID- 17552007
TI  - Long-term results of subtotal colectomy with cecorectal anastomosis for isolated
      colonic inertia.
AB  - AIM: To evaluate the results of sub total colectomy with cecorectal anastomosis
      (STC-CRA) for isolated colonic inertia (CI). METHODS: Fourteen patients (mean age
      57.5 +/- 16.5 year) underwent surgery for isolated CI between January 1986 and
      December 2002. The mean frequency of bowel motions with the aid of laxatives was
      1.2 +/- 0.6 per week. All subjects underwent colonoscopy, anorectal manometry,
      cinedefaecography and colonic transit time (CTT). CI was defined as diffuse
      markers delay on CTT without evidence of pelvic floor dysfunction. All patients
      underwent STC-CRA. Long-term follow-up was obtained prospectively by clinical
      visits between October 2005 and February 2006 at a mean of 10.5 +/- 3.6 years
      (range 5-16 years) during which we considered the number of stool emissions, the
      presence of abdominal pain or digitations, the use of pain killers, laxatives
      and/or fibers. Patients were also asked if they were satisfied with the surgery.
      RESULTS: There was no postoperative mortality. Postoperative complications
      occurred in 21.4% (3/14). At the end of follow-up, bowel frequency was
      significantly (P < 0.05) increased to a mean of 4.8 +/- 7.5 per day (range 1-30).
      One patient reported disabling diarrhea. Two patients used laxatives less than
      three times per month without complaining of what they called constipation.
      Overall, 78.5% of patients would have chosen surgery again if necessary.
      CONCLUSION: STC-CRA is feasible and safe in patients with CI achieving 79% of
      success at a mean follow-up of 10.5 years. A prospective controlled evaluation is
      warranted to verify the advantages of this surgical approach in patients with CI.

PMID- 17552008
TI  - Effects of granulocyte-colony stimulating factor on peritoneal defense mechanisms
      and bacterial translocation after administration of systemic chemotherapy in
      rats.
AB  - AIM: To investigate the effects of granulocyte-colony stimulating factor (G-CSF)
      on peritoneal defense mechanisms and bacterial translocation after systemic 5
      Fluorouracil (5-FU) administration. METHODS: Thirty Wistar albino rats were
      divided into three groups; the control, 5-FU and 5-FU + G-CSF groups. We measured
      bactericidal activity of the peritoneal fluid, phagocytic activity of
      polymorphonuclear leucocytes in the peritoneal fluid, total peritoneal cell
      counts and cell types of peritoneal washing fluid. Bacterial translocation was
      quantified by mesenteric lymph node, liver and spleen tissue cultures. RESULTS:
      Systemic 5-FU reduced total peritoneal cell counts, neutrophils and macrophage
      numbers. It also altered bactericidal activity of the peritoneal fluid and
      phagocytic activity of polymorphonuclear leucocytes in the peritoneal fluid. 5-FU
      also caused significant increase in frequencies of bacterial translocation at the
      liver and mesenteric lymph nodes. G-CSF decreased bacterial translocation, it
      significantly enhanced bactericidal activity of the peritoneal fluid and
      phagocytic activity of polymorphonuclear leucocytes in the peritoneal fluid. It
      also increased total peritoneal cell counts, neutrophils and macrophage numbers.
      CONCLUSION: Systemic 5-FU administration caused bacterial translocation,
      decreased the bactericidal activity of peritoneal fluid and phagocytic activity
      of polymorphonuclear leucocytes in the peritoneal fluid. G-CSF increased both
      bactericidal activity of the peritoneal fluid and phagocytic activity of
      polymorphonuclear leucocytes in the peritoneal fluid, and prevented the bacterial
      translocation. We conclude that intraperitoneal GCSF administration protects the
      effects of systemic 5-FU on peritoneal defense mechanisms.

PMID- 17552009
TI  - Study of the duodenal contractile activity during antral contractions.
AB  - AIM: To investigate the hypothesis that duodenal bulb (DB) inhibition on pyloric
      antrum (PA) contraction is reflex. METHODS: Balloon (condom)-tipped tube was
      introduced into 1(st) duodenum (DD) and a manometric tube into each of PA and DD.
      Duodenal and antral pressure response to duodenal and then PA balloon distension
      with saline was recorded. These tests were repeated after separate
      anesthetization of DD and PA. RESULTS: Two and 4 mL of 1(st) DD balloon
      distension produced no pressure changes in DD or PA (10.7 +/- 1.2 vs 9.8 +/- 1.2,
      11.2 +/- 1.2 vs 11.3 +/- 1.2 on H(2)O respectively, P > 0.05). Six mL distension
      effected 1(st) DD pressure rise (30.6 +/- 3.4 cm H(2)O, P < 0.01) and PA pressure
      decrease (6.2 +/- 1.4 cm H(2)O, P < 0.05); no response in 2(nd), 3(rd) and 4(th)
      DD. There was no difference between 6, 8, and 10 mL distensions. Ten mL PA
      distension produced no PA or 1(st) DD pressure changes (P > 0.05). Twenty mL
      distension increased PA pressure (92.4 +/- 10.7 cm H(2)O, P < 0.01) and decreased
      1(st) DD pressure (1.6 +/- 0.3 cm H(2)O, P < 0.01); 30, 40, and 50 mL distension
      produced the same effect as the 20 mL distension (P > 0.05). PA or DD distension
      after separate anesthetization produced no significant pressure changes in PA or
      DD. CONCLUSION: Large volume DD distension produced DD pressure rise denoting DD
      contraction and PA pressure decline denoting PA relaxation. PA relaxation upon DD
      contraction is postulated to be mediated through a reflex which we call duodeno
      antral reflex. Meanwhile, PA distension effected DD relaxation which we suggest
      to be reflex and termed antro-duodenal reflex. It is suggested that these 2
      reflexes, could act as investigative tools in diagnosis of gastroduodenal
      motility disorders.

PMID- 17552010
TI  - Clinical presentation and genotype of hepatitis delta in Karachi.
AB  - AIM: To assess the clinical presentation and genotypes of delta hepatitis in
      local population. METHODS: In this prospective study, 39 consecutive patients who
      were positive for HBsAg and hepatitis D virus (HDV) antibody were included. The
      patients were divided in two groups on the basis of presence or absence of HDV
      RNA and a comparative study was done. Genotype of HDV was determined in PCR
      positive patients. RESULTS: Overall there is male dominance, in which 34 patients
      out of 39 (87.2%) were male. Twenty (51%) patients were from the adjacent areas
      of three provinces; Sindh, Punjab and Balochistan indicating the higher
      prevalence of delta hepatitis in this mid region of Pakistan. Patients of all age
      groups were affected with delta hepatitis (median 31.5 years, range 12-75). HDV
      RNA was detectable in 23 patients (59%). All the HDV strains belonged to genotype
      I. HBV DNA was detectable only in 3 cases who were also HBeAg and HDV RNA
      positive. Patients with detectable HDV RNA were younger than patients with
      undetectable RNA; mean age 29.7 +/- 12.8 years vs 36.8 +/- 15.2. There were no
      statistically significant differences in the clinical presentation and routine
      biochemical profile of patients with detectable or undetectable HDV RNA. Clinical
      cirrhosis was present in 19 (49%) patients; 12 with detectable RNA and 7 with
      undetectable HDV RNA (P = 0.748). Decompensated disease was seen in eight
      patients; five and three respectively from each group. Four patients with
      undetectable RNA and two patients with detectable RNA had normal ALT and
      ultrasound abdomen. CONCLUSION: HDV may infect at any age, usually young adult
      males. Genotype I is prevalent. With time some of the patients become HDV RNA
      negative or asymptomatic carrier. Most of the patients have suppressed HBV DNA
      replication. Significant numbers of patients have cirrhosis.

PMID- 17552011
TI  - Protein profile of human hepatocarcinoma cell line SMMC-7721: identification and
      functional analysis.
AB  - AIM: To investigate the protein profile of human hepatocarcinoma cell line SMMC
      7721, to analyze the specific functions of abundant expressed proteins in the
      processes of hepatocarcinoma genesis, growth and metastasis, to identify the
      hepatocarcinoma-specific biomarkers for the early prediction in diagnosis, and to
      explore the new drug targets for liver cancer therapy. METHODS: Total proteins
      from human hepatocarcinoma cell line SMMC-7721 were separated by two-dimensional
      electrophoresis (2DE). The silver-stained gel was analyzed by 2DE software Image
      Master 2D Elite. Interesting protein spots were identified by peptide mass
      fingerprinting based on matrix-assisted laser desorption/ionization time-of
      flight mass spectrometry (MALDI-TOF-MS) and database searching. RESULTS: We
      obtained protein profile of human hepatocarcinoma cell line SMMC-7721. Among the
      twenty-one successfully identified proteins, mitofilin, endoplasmic reticulum
      protein ERp29, ubiquinol-cytochrome C reductase complex core protein I,
      peroxisomal enoyl CoA hydratase, peroxiredoxin-4 and probable 3-oxoacid CoA
      transferase 1 precursor were the six novel proteins identified in human
      hepatocarcinoma cells or tissues. Specific functions of the identified heat-shock
      proteins were analyzed in detail, and the results suggested that these proteins
      might promote tumorigenesis via inhibiting cell death induced by several cancer
      related stresses or via inhibiting apoptosis at multiple points in the apoptotic
      signal pathway. Other identified chaperones and cancer-related proteins were also
      analyzed. CONCLUSION: Based on the protein profile of SMMC-7721 cells, functional
      analysis suggests that the identified chaperones and cancer-related proteins have
      their own pathways to contribute to the tumorigenesis, tumor growth and
      metastasis of liver cancer. Furthermore, proteomic analysis is indicated to be
      feasible in the cancer study.

PMID- 17552012
TI  - Pancreas duodenal homeobox-1 expression and significance in pancreatic cancer.
AB  - AIM: To study the correlations of Pancreas duodenal homeobox-1 with pancreatic
      cancer characteristics, including pathological grading, TNM grading, tumor
      metastasis and tumor cell proliferation. METHODS: Reverse transcriptase
      polymerase chain reaction (RT-PCR) was used to detect PDX-1 mRNA expression in
      pancreatic cancer tissue and normal pancreatic tissue. The expression of PDX-1
      protein was measured by Western blot and immunohistochemistry.
      Immunohistochemistry was also used to detect proliferative cell nuclear antigen
      (PCNA). Correlations of PDX-1 with pancreatic cancer characteristics, including
      pathological grading, TNM grading, tumor metastasis and tumor cell proliferation,
      were analyzed by using c2 test. RESULTS: Immunohistochemistry showed that 41.1%
      of pancreatic cancers were positive for PDX-1 expression, but normal pancreatic
      tissue except islets showed no staining for PDX-1. In consistent with the result
      of imunohistochemistry, Western blot showed that 37.5% of pancreatic cancers were
      positive for PDX-1. RT-PCR showed that PDX-1 expression was significantly higher
      in pancreatic cancer tissues than normal pancreatic tissues (2(-3.56 +/- 0.35) vs
      2(-8.76 +/- 0.14), P < 0.01). Lymph node metastasis (P < 0.01), TNM grading (P <
      0.05), pathological grading (P < 0.05) and tumor cell proliferation (P < 0.01)
      were significantly correlated with PDX-1 expression levels. CONCLUSION: PDX-1 is
      re-expressed in pancreatic cancer, and PDX-1-positive pancreatic cancer cells
      show more malignant potential compared to PDX-1-negative cells. Therefore, PDX-1
      positive cells may be tumor stem cells and PDX-1 may act as alternate surface
      marker of pancreatic cancer stem cells.

PMID- 17552013
TI  - Surgical management of 143 patients with adult primary retroperitoneal tumor.
AB  - AIM: To analyze the surgical management of adult primary retroperitoneal tumors
      (APRT) and the factors influencing the outcome after operation. METHODS: Data of
      143 cases of APRT from 1990 to 2003 in the First Affiliated Hospital of China
      Medical University were evaluated retrospectively. RESULTS: A total of 143 cases
      of APRT were treated surgically. Among them, 122 (85.3%) underwent complete
      resection, 16 (11.2%) incomplete resection, and 3 (3%) surgical biopsies. Twenty
      nine (20.2%) underwent tumor resection plus multiple organ resections. Ninety
      five malignant cases were followed up for 1 mo to 5 years. The 1-year, 3-year,
      and 5-year survival rates of the patients subject to complete resection was
      94.9%, 76.6% and 34.3% and that of patients with incomplete resection was 80.4%,
      6.7%, and 0%, respectively (P < 0.001). The Cox multi-various regression analysis
      showed the completeness of tumor, sex and histological type were associated
      closely with local recurrence. CONCLUSION: Sufficient preoperative preparation
      and complete tumor resection play important roles in reducing recurrence and
      improving survival.

PMID- 17552014
TI  - Expression level of beta-catenin is associated with prognosis of esophageal
      carcinoma.
AB  - AIM: To examine the association of beta-catenin with the clinicopathologic
      features and prognosis of esophageal squamous cell carcinoma (ESCC). METHODS:
      Beta-catenin mRNA expression level in 40 ESCC patients (28 males and 12 females,
      age range 38-82 years, median 60 years) was analyzed by real-time PCR. Beta
      catenin mRNA expression levels in tumor cells were categorized as weaker (level
      1) or equal to or stronger (level 2) than those in endothelial cells. We examined
      the correlation between the beta-catenin expression and the clinicopathological
      factors and prognosis of ESCC patients. RESULTS: Level 2 beta-catenin expression
      was found in 29 patients. ESCC with level 2 expression had a higher rate of
      lymphnode metastasis (0.0776 +/- 0.0369 vs 0.3413 +/- 0.1803, P < 0.001) and
      deeper tumor invasion (0.0751 +/- 0.0356 vs 0.3667 +/- 0.1928, P < 0.001), and a
      poorer survival rate (P = 0.0024) than ESCC with level 1 expression. CONCLUSION:
      Beta-catenin expression in ESCC is of great importance.

PMID- 17552015
TI  - Study of the expressions of p53 and bcl-2 genes, the telomerase activity and
      apoptosis in GIST patients.
AB  - AIM: To explore the relationship between clinicobiological behavior and the
      expression levels of telomerase activity, apoptosis, p53 gene and bcl-2 gene in
      gastrointestinal stromal tumors (GISTs). METHODS: The intensity of telomerase
      activity, apoptosis, p53 and bcl-2 expression in GISTs were detected by telomeric
      repeat amplification protocol, in situ end-labeling technique, and
      immunohistochemistry, respectively. RESULTS: The positive rates of telomerase
      activity of malignant GIST, potential malignant GIST and benign GIST were 85%
      (17/20), 22.8% (2/9) and 0 (0/9), respectively. The apoptosis indices of
      malignant GIST, potential malignant GIST, and benign GIST were 11.7 +/- 5.4, 30.2
      +/- 5.6 and 45.2 +/- 7.2, respectively. The intensity of telomerase activity and
      apoptosis were related to the biological characteristics of GISTs (85% vs 22.8%,
      0, 0; P < 0.01 or 11.7 +/- 5.4 vs 30.2 +/- 5.6, 45.2 +/- 7.2, 72.1 +/- 9.3; P <
      0.05). The intensity of telomerase activity was negatively correlated with
      cellular apoptosis (22.9 +/- 8.4 vs 9.5 +/- 5.7, P < 0.01). The intensity of
      telomerase activity was positively correlated with p53, bcl-2 expression (40.0%
      vs 78.9%, 40.0% vs 84.2%; P < 0.05). CONCLUSION: The detection of telomerase
      activity, apoptosis and its control genes in GIST will be helpful for the
      discrimination of the malignant and benign GIST and evaluation of the prognosis.

PMID- 17552016
TI  - Effect of sunitinib on metastatic gastrointestinal stromal tumor in patients with
      neurofibromatosis type 1: a case report.
AB  - Gastrointestinal stromal tumor (GIST) represents the most common mesenchymal
      malignancy of the gastrointestinal (GI) tract. In neurofibromatosis (NF), the
      increased incidence of tumor needs to be considered even in non-symptomatic
      individuals. Patients with neurofibromatosis NF type 1 have an increased risk of
      developing GI tumors including rare types such as GIST. We report a case of GIST
      in a 53-year-old male patient with neurofibromatosis. The patient was diagnosed
      with NF four years ago and his medical history revealed that he was hospitalized
      5 times with a provisional diagnosis of massive lower gastrointestinal bleeding.
      GIST was diagnosed at explorative laparotomy and the tumor was 21 cm multiply 13
      cm multiply 7 cm in size. Immunohistochemical examination showed that vimentin,
      actin and CD117 were positive. Computerized tomography showed peritoneal implants
      three months later. Imatinib mesylate (600 mg/d) was initiated. However, control
      computerized tomography revealed liver and omental metastasis. The dosage was
      elevated to 800 mg/d. Despite high dosage, the progression of the metastatic
      lesions continued in the liver and omentum. The patient started oral sunitinib
      malate (Sutent) Pfizer Inc, New York, NY, USA) 50 mg per day for 4 consecutive
      weeks, followed by 2 wk off per treatment cycle. The metastatic lesions in the
      liver and omentum were decreased in size after four courses, suggesting that
      sunitinib is also an effective treatment modality for metastatic GIST in NF
      patients.

PMID- 17552017
TI  - Ectopic fascioliasis mimicking a colon tumor.
AB  - Fasciola hepatica, a leaf shaped trematode that is common in cattle, sheep and
      goats, is acquired by eating raw water plants like watercress or drinking water
      infected with the encysted form of the parasite. The varied clinical
      presentations of fascioliasis still make a high index of suspicion mandatory.
      Besides having a wide spectrum of hepatobiliary symptoms like obstructive
      jaundice, cholangitis and liver cirrhosis, the parasitic infection also has
      extrabiliary manifestations. Until recently, extrahepatic fascioliasis has been
      reported in the subcutaneous tissue, brain, lungs, epididymis, inguinal lymph
      nodes, stomach and the cecum. In this report, a strange manifestation of the
      fasciola infection in a site other than the liver, a colonic fascioliasis, is
      presented.

PMID- 17552018
TI  - Celiac disease manifested by polyneuropathy and swollen ankles.
AB  - A 27-year-old male started to have his ankles swollen during his military
      service. He was examined at a military hospital where electromyoneurography
      showed the signs of distal sensory-motor polyneuropathy with axon demyelinization
      and weak myopathic changes, whereas histopathological examination of
      gastrocnemius muscle biopsy revealed some mild and nonspecific myopathy. Besides,
      he was found to have subcutaneous ankle tissue edemas and hypertransaminasemia.
      Due to these reasons, he was dismissed from the military service and examined at
      another hospital where bone osteodensitometry revealed low bone mineral density
      of the spine. However, his medical problems were not resolved and after the
      second discharge from hospital he was desperately seeing doctors from time to
      time. Finally, at our institution he was shown to have celiac disease (CD) by
      positive serology (antitissue transglutaminase and antiendomysial antibodies) and
      small bowel mucosal histopathological examination, which showed total small bowel
      villous atrophy. Three months after the initiation of gluten-free diet, his ankle
      edema disappeared, electromyoneurographic signs of polyneuropathy improved and
      liver aminotransferases normalized. Good knowledge of CD extraintestinal signs
      and serologic screening are essential for early CD recognition and therapy.

PMID- 17552019
TI  - Therapeutic strategies for pediatric non-alcoholic fatty liver disease: a
      challenge for health care providers.
AB  - Non-alcoholic steato-hepatitis (NASH) is related to insulin resistance and, thus,
      frequently occurs as part of the metabolic changes that accompany obesity,
      diabetes and hyperlipidemia. In childhood, the overwhelming boost of obesity and
      its co-morbidities have lead to the extraordinarily increased prevalence of NASH.
      Establishing effective therapeutic strategies to treat the disease represents the
      challenge for hepatologists and gastroenterologists in the next decade.
      Therapeutic approaches have aimed at treating associated conditions (obesity,
      insulin resistance, hyperlipemia, etc) or reducing liver oxidative damage
      (vitamin E).

PMID- 17552020
TI  - Insulin and heparin in treatment of hypertriglyceridemia-induced pancreatitis.

PMID- 17552022
TI  - Recent advances in hepatitis C virus research and understanding the biology of
      the virus.

PMID- 17552021
TI  - Social learning contributions to the etiology and treatment of functional
      abdominal pain and inflammatory bowel disease in children and adults.
AB  - This paper reviews empirical work on cognitive and social learning contributions
      to the etiology and treatment of illness behavior associated with functional
      abdominal pain and inflammatory bowel disease. A particular emphasis is placed on
      randomized controlled trials, the majority of which are multi-modal in
      orientation, incorporating elements of cognitive behavioral therapy, social
      learning, and relaxation. Based on this review, we offer methodological and
      clinical suggestions: (1) Research investigations should include adequate sample
      sizes, long-term follow-up assessments, and a credible, active control group. (2)
      Standard gastrointestinal practice should include, when appropriate, learning
      opportunities for patients and family members, for example, instruction regarding
      the encouragement of wellness behavior.

PMID- 17552023
TI  - Hepatitis C virus proteins.
AB  - Hepatitis C virus (HCV) encodes a single polyprotein, which is processed by
      cellular and viral proteases to generate 10 polypeptides. The HCV genome also
      contains an overlapping +1 reading frame that may lead to the synthesis of an
      additional protein. Until recently, studies of HCV have been hampered by the lack
      of a productive cell culture system. Since the identification of HCV genome
      approximately 17 years ago, structural, biochemical and biological information on
      HCV proteins has mainly been obtained with proteins produced by heterologous
      expression systems. In addition, some functional studies have also been confirmed
      with replicon systems or with retroviral particles pseudotyped with HCV envelope
      glycoproteins. The data that have accumulated on HCV proteins begin to provide a
      framework for understanding the molecular mechanisms involved in the major steps
      of HCV life cycle. Moreover, the knowledge accumulated on HCV proteins is also
      leading to the development of antiviral drugs among which some are showing
      promising results in early-phase clinical trials. This review summarizes the
      current knowledge on the functions and biochemical features of HCV proteins.

PMID- 17552024
TI  - Genetic diversity of the hepatitis C virus: impact and issues in the antiviral
      therapy.
AB  - The hepatitis C Virus (HCV) presents a high degree of genetic variability which
      is explained by the combination of a lack of proof reading by the RNA dependant
      RNA polymerase and a high level of viral replication. The resulting genetic
      polymorphism defines a classification in clades, genotypes, subtypes, isolates
      and quasispecies. This diversity is known to reflect the range of responses to
      Interferon therapy. The genotype is one of the predictive parameters currently
      used to define the antiviral treatment strategy and the chance of therapeutic
      success. Studies have also reported the potential impact of the viral genetic
      polymorphism in the outcome of antiviral therapy in patients infected by the same
      HCV genotype. Both structural and non structural genomic regions of HCV have been
      suggested to be involved in the Interferon pathway and the resistance to
      antiviral therapy. In this review, we first detail the viral basis of HCV
      diversity. Then, the HCV genetic regions that may be implicated in resistance to
      therapy are described, with a focus on the structural region encoded by the E2
      gene and the non-structural genes NS3, NS5A and NS5B. Both mechanisms of the
      Interferon resistance and of the new antiviral drugs are described in this
      review.

PMID- 17552025
TI  - New animal models for hepatitis C viral infection and pathogenesis studies.
AB  - Hepatitis C virus (HCV) is a major cause of chronic liver disease, cirrhosis and
      hepatocellular carcinoma (HCC). In man, the pathobiological changes associated
      with HCV infection have been attributed to both the immune system and direct
      viral cytopathic effects. Until now, the lack of simple culture systems to infect
      and propagate the virus has hampered progress in understanding the viral life
      cycle and pathogenesis of HCV infection, including the molecular mechanisms
      implicated in HCV-induced HCC. This clearly demonstrates the need to develop
      small animal models for the study of HCV-associated pathogenesis. This review
      describes and discusses the development of new HCV animal models to study viral
      infection and investigate the direct effects of viral protein expression on liver
      disease.

PMID- 17552026
TI  - Epidemiology of hepatitis C virus infection.
AB  - Globally, hepatitis C virus (HCV) has infected an estimated 130 million people,
      most of whom are chronically infected. HCV-infected people serve as a reservoir
      for transmission to others and are at risk for developing chronic liver disease,
      cirrhosis, and primary hepatocellular carcinoma (HCC). It has been estimated that
      HCV accounts for 27% of cirrhosis and 25% of HCC worldwide. HCV infection has
      likely been endemic in many populations for centuries. However, the wave of
      increased HCV-related morbidity and mortality that we are now facing is the
      result of an unprecedented increase in the spread of HCV during the 20th century.
      Two 20th century events appear to be responsible for this increase; the
      widespread availability of injectable therapies and the illicit use of injectable
      drugs.

PMID- 17552027
TI  - Cell culture systems for the hepatitis C virus.
AB  - Since the discovery of HCV in 1989, the lack of a cell culture system has
      hampered research progress on this important human pathogen. No robust system has
      been obtained by empiric approaches, and HCV cell culture remained hypothetical
      until 2005. The construction of functional molecular clones has served as a
      starting point to reconstitute a consensus infectious cDNA that was able to
      transcribe infectious HCV RNAs as shown by intrahepatic inoculation in a
      chimpanzee. Other consensus clones have been selected and established in a human
      hepatoma cell line as replicons, i.e. self-replicating subgenomic or genomic
      viral RNAs. However, these replicons did not support production of infectious
      virus. Interestingly, some full-length replicons could be established without
      adaptive mutations and one of them was able to replicate at very high levels and
      to release virus particles that are infectious in cell culture and in vivo. This
      new cell culture system represents a major breakthrough in the HCV field and
      should enable a broad range of basic and applied studies to be achieved.

PMID- 17552028
TI  - The interferon inducing pathways and the hepatitis C virus.
AB  - The innate immune response is triggered by a variety of pathogens, including
      viruses, and requires rapid induction of type I interferons (IFN), such as
      IFNbeta and IFNalpha. IFN induction occurs when specific pathogen motifs bind to
      specific cellular receptors. In non-professional immune, virally-infected cells,
      IFN induction is essentially initiated after the binding of dsRNA structures to
      TLR3 receptors or to intracytosolic RNA helicases, such as RIG-I/MDA5. This leads
      to the recruitment of specific adaptors, such as TRIF for TLR3 and the
      mitochondrial-associated IPS-1/VISA/MAVS/CARDIF adapter protein for the RNA
      helicases, and the ultimate recruitment of kinases, such as MAPKs, the canonical
      IKK complex and the TBK1/IKKepsilon kinases, which activate the transcription
      factors ATF-2/c-jun, NF-kappaB and IRF3, respectively. The coordinated action of
      these transcription factors leads to induction of IFN and of pro-inflammatory
      cytokines and to the establishment of the innate immune response. HCV can cleave
      both the adapters TRIF and IPS-1/VISA/MAVS/CARDIF through the action of its
      NS3/4A protease. This provokes abrogation of the induction of the IFN and
      cytokine pathways and favours viral propagation and presumably HCV chronic
      infection.

PMID- 17552029
TI  - Hepatocellular carcinoma in patients with hepatitis C virus-related chronic liver
      disease.
AB  - Hepatitis C virus (HCV) is a major cause of hepatocellular carcinoma (HCC)
      worldwide due to the high prevalence of HCV infection and the high rate of HCC
      occurrence in patients with HCV cirrhosis. A striking increase in HCC incidence
      has been observed during the past decades in most industrialized countries,
      partly related to the growing number of patients infected by HCV. HCC is
      currently the main cause of death in patients with HCV-related cirrhosis, a fact
      that justifies screening as far as curative treatments apply only in patients
      with small tumors. As a whole, treatment options are similar in patients with
      cirrhosis whatever the cause. Chemoprevention could be also helpful in the near
      future. It is strongly suggested that antiviral treatment of HCV infection could
      prevent HCC occurrence, even in cirrhotic patients, mainly when a sustained
      virological response is obtained.

PMID- 17552030
TI  - Hepatitis C virus: virology, diagnosis and management of antiviral therapy.
AB  - Hepatitis C virus (HCV) infects approximately 170 million individuals worldwide.
      Prevention of HCV infection complications is based on antiviral therapy with the
      combination of pegylated interferon alfa and ribavirin. The use of serological
      and virological tests has become essential in the management of HCV infection in
      order to diagnose infection, guide treatment decisions and assess the virological
      response to antiviral therapy. Anti-HCV antibody testing and HCV RNA testing are
      used to diagnose acute and chronic hepatitis C. The HCV genotype should be
      systematically determined before treatment, as it determines the indication, the
      duration of treatment, the dose of ribavirin and the virological monitoring
      procedure. HCV RNA monitoring during therapy is used to tailor treatment duration
      in HCV genotype 1 infection, and molecular assays are used to assess the end-of
      treatment and, most importantly the sustained virological response, i.e. the
      endpoint of therapy.

PMID- 17552032
TI  - Immunotherapy of hepatoma with a monoclonal antibody against murine endoglin.
AB  - AIM: To explore the capability of a monoclonal antibody (mAb) against murine
      endoglin to inhibit tumor angiogenesis and suppression of hepatoma growth in
      murine models. METHODS: A monoclonal antibody against murine endoglin was
      purified by affinity chromatography and passively transfused through tail veins
      in two murine hepatoma models. Tumor volume and survival time were observed at
      three-day intervals for 48 d. Microvessels in tumor tissues were detected by
      immunohistochemistry against CD31, and angiogenesis in vivo was determined by
      alginate encapsulated assay. In addition, tumor cell apoptosis was detected by
      TUNEL assay. RESULTS: Passive immunotherapy with anti-endoglin mAb could
      effectively suppress tumor growth, and prolonged the survival time of hepatoma
      bearing mice. Angiogenesis was apparently inhibited within the tumor tissues, and
      the vascularization of alginate beads was also reduced in the mice passively
      transfused with anti-endoglin mAb. In addition, increased apoptotic cells were
      observed within the tumor tissues from the mice passively transfused with anti
      endoglin mAb. CONCLUSION: Passive immunotherapy with anti-endoglin mAb
      effectively inhibits tumor growth via inhibiting tumor angiogenesis and
      increasing tumor cell apoptosis, which may be highly correlated with the blockage
      of endoglin-related signal pathway induced by anti-endoglin mAb.

PMID- 17552031
TI  - Hepatitis C virus-related lymphoproliferative disorders: an overview.
AB  - Hepatitis C virus (HCV) is a global health problem affecting 3% of the world's
      population (about 180 million) and a cause of both hepatic and extrahepatic
      diseases. B-cell lymphoproliferative disorders, whose prototype is mixed
      cryoglobulinemia, represent the most closely related as well as the most
      investigated HCV-related extrahepatic disorder. The association between
      extrahepatic (lymphoma) as well as hepatic malignancies (hepatocellular
      carcinoma) has justified the inclusion of HCV among human cancer viruses. HCV
      associated manifestations also include porphyria cutanea tarda, lichen planus,
      nephropathies, thyreopathies, sicca syndrome, idiopathic pulmonary fibrosis,
      diabetes, chronic polyarthritis, sexual dysfunctions,
      cardiopathy/atherosclerosis, and psychopathological disorders. A pathogenetic
      link between HCV virus and some lymphoproliferative disorders was confirmed by
      their responsiveness to antiviral therapy, which is now considered the first
      choice treatment. The aim of the present paper is to provide an overview of
      extrahepatic manifestations of HCV infection with particular attention to B-cell
      lymphoproliferative disorders. Available pathogenetic hypotheses and suggestions
      about the most appropriate, currently available, therapeutic approaches will also
      be discussed.

PMID- 17552033
TI  - Synergistic anti-tumor effect of recombinant chicken fibroblast growth factor
      receptor-1-mediated anti-angiogenesis and low-dose gemcitabine in a mouse colon
      adenocarcinoma model.
AB  - AIM: To evaluate whether the combination of recombinant chicken fibroblast growth
      factor receptor-1 (FGFR-1) protein vaccine (cFR-1) combined with low-dose
      gemcitabine would improve anti-tumor efficacy in a mouse CT26 colon
      adenocarcinoma (CT26) model. METHODS: The CT26 model was established in BABL/c
      mice. Seven days after tumor cell injection, mice were randomly divided into four
      groups: combination therapy, cFR-1 alone, gemcitabine alone, and normal saline
      groups. Tumor growth, survival rate of tumor-bearing mice, and systemic toxicity
      were observed. The presence of anti-tumor auto-antibodies was detected by Western
      blot analysis and enzyme-linked immunospot assay, microvessel density (MVD) of
      the tumors and tumor cell proliferation were detected by Immunohistochemistry
      staining, and tumor cell apoptosis was detected by TdT-mediated biotinylated-dUTP
      nick end label staining. RESULTS: The combination therapy results in apparent
      decreases in tumor volume, microvessel density and tumor cell proliferation, and
      an increase in apoptosis without obvious side-effects as compared with either
      therapy alone or normal control groups. Also, both auto-antibodies and the
      antibody-producing B cells against mouse FGFR-1 were detected in mice immunized
      with cFR-1 vaccine alone or with combination therapy, but not in non-immunized
      mice. In addition, the deposition of auto-antibodies on endothelial cells from
      mice immunized with cFR-1 was observed by immunofluorescent stain-ing, but not on
      endothelial cells from control groups. Synergistic indexes of tumor volume, MVD,
      cell apoptosis and proliferation in the combination therapy group were 1.71 vs
      1.15 vs 1.11 and 1.04, respectively, 31 d after tumor cell injection. CONCLUSION:
      The combination of cFR-1-mediated anti-angiogenesis and low-dose gemcitabine
      synergistically enhances the anti-tumor activity without overt toxicity in mice.

PMID- 17552034
TI  - High expression of hepatitis B virus based vector with reporter gene in hepatitis
      B virus infection system.
AB  - AIM: To construct a hepatitis B virus (HBV)-based vector with a reporter gene and
      to establish an HBV infection system to evaluate the availability of the vector.
      METHODS: The HBV-based vectors with green fluorescence protein (GFP) were
      packaged into the liver of immunodeficient mice through transfer and helper
      plasmid using hydrodynamic technology. Wild type HBV (wt HBV) was provided by
      plasmid MC2009. Primary human hepatocytes (PHH) were isolated and infected with
      recombinant HBV (rHBV) or wt HBV. GFP expression was monitored by confocal and
      flow cytometry. HBV DNA and HBV surface antigen (HBSAg) were analyzed by PCR and
      ELISA. RESULTS: 3 x 10(7) wt HBV copies/mL and 5 x 10(6) rHBV copies/mL were
      collected from mice serum. In the wt HBV infected group, HBV progeny was 2 x
      10(7) copies/mL and HBSAg was 770 ng/mL. In the rHBV infected group, GFP
      fluorescence was detected on d 3 post-infection and over 85% of the parenchymal
      cells expressed green fluorescence on d 12 post-infection. Compared with wt HBV
      in the PHH infection system, no rHBV DNA or HBSAg were detected in PHH culture
      media. CONCLUSION: An effective HBV based vector was developed, which proved to
      be a useful HBV infection system. This vector and infection system can be applied
      to develop a therapeutic vector and study the HBV life cycle and viral
      pathogenesis.

PMID- 17552035
TI  - Relationship of quantitative structure and pharmacokinetics in fluoroquinolone
      antibacterials.
AB  - AIM: To study the relationship between quantitative structure and
      pharmacokinetics (QSPkR) of fluoroquinolone antibacterials. METHODS: The
      pharmacokinetic (PK) parameters of oral fluoroquinolones were collected from the
      literature. These pharmacokinetic data were averaged, 19 compounds were used as
      the training set, and 3 served as the test set. Genetic function approximation
      (GFA) module of Cerius(2) software was used in QSPkR analysis. RESULTS: A small
      volume and large polarizability and surface area of substituents at C-7
      contribute to a large area under the curve (AUC) for fluoroquinolones. Large
      polarizability and small volume of substituents at N-1 contribute to a long half
      life elimination. CONCLUSION: QSPkR models can contribute to some
      fluoroquinolones antibacterials with excellent pharmacokinetic properties.

PMID- 17552038
TI  - Telerobotic-assisted laparoscopic abdominoperineal resection for low rectal
      cancer: report of the first case in Hong Kong and China with an updated
      literature review.
AB  - Telerobotic surgery is the most advanced development in the field of minimally
      invasive surgery. The da Vinci surgical system, which is currently the most
      widely used telerobotic device, was approved by the Food and Drug Administration
      of the United States of America for clinical use in all abdominal operations in
      July 2000. The first da Vinci surgical system in China was installed in November
      2005 at our institution. We herein report the first telerobotic-assisted
      laparoscopic abdominoperineal resection using the 3-arm da Vinci surgical system
      for low rectal cancer in Hong Kong and China, which was performed in August 2006.
      The operative time and blood loss were 240 min and 200 mL, respectively. There
      was no complication, and the patient was discharged on postoperative day five. An
      updated review of published literature on telerobotic-assisted colorectal surgery
      is included in this report, with special emphasis on its advantages and
      limitations.

PMID- 17552036
TI  - Extrapulmonary sarcoidosis of liver and pancreas: a case report and review of
      literature.
AB  - Sarcoidosis is a chronic multisystemic granulomatous disease of unknown origin,
      which can involve nearly all organs. In the case of an infrequent
      gastrointestinal tract involvement in systemic sarcoidosis, granulomas of the
      liver are most commonly described while isolated pancreatic sarcoid lesions are
      rarely seen. We report a case of systemic sarcoidosis with exclusive
      extrapulmonal involvement of the liver and the pancreas in a 71-year-old white
      man. The diagnosis of liver involvement was confirmed by biopsy. Pancreatic
      surgery was needed because preoperative evaluation could not exclude pancreatic
      cancer and for biliary decompression. An extensive literature review of systemic
      sarcoidosis, focusing on reported cases with unusual presentation of sarcoidosis
      in the liver and the pancreas, its diagnosis, treatment, and prognosis was made.

PMID- 17552037
TI  - Cecal lipoma with pseudomalignant features: a case report and review of the
      literature.
AB  - Colonic lipoma is a well-documented benign neoplasia, endoscopically appearing as
      a smooth round yellowish polyp with a thick stalk or broad-based attachment. We
      describe a 63-year old woman with persistent abdominal pain, in whom colonoscopy
      revealed a cecal mass with malignant features. Based on the colonoscopy findings,
      right hemicolectomy was laparoscopically performed for a presumptive diagnosis of
      a cecal adenocarcinoma, but histological examination revealed a colonic lipoma
      with overlying mucosal ulceration.

PMID- 17552039
TI  - Pain relief in osteoarthritis: patients' willingness to risk medication-induced
      gastrointestinal, cardiovascular, and cerebrovascular complications.
AB  - OBJECTIVE: Information concerning patients' preferences for the treatment of
      osteoarthritis (OA) is limited. We examined patients' attitudes toward the
      acceptability of gastrointestinal, cardiac, and cerebrovascular events in order
      to obtain pain relief from OA. METHODS: Patients responded to a set of threshold
      technique tasks. Each task described 2 treatment options, their levels of pain
      relief, and the risks of side effects. The risk for the side effect under
      investigation was then systematically increased to reveal the maximal acceptable
      risk increment associated with the pain reduction. RESULTS: Of 196 patients,
      22.3% and 14.7% were unwilling to accept any additional risk of stomach bleed or
      heart attack/stroke for 2-point and 5-point pain reductions, respectively.
      Patients were willing to accept significantly more risk for a 5-point pain
      reduction than for a 2-point pain reduction in stomach bleed and heart
      attack/stroke scenarios. Patients also accepted significantly greater additional
      risks of stomach bleed compared to heart attack/stroke for 2-point and 5-point
      pain reductions. CONCLUSION: Most patients with OA are willing to accept some
      additional risk of stomach bleed and heart attack/stroke to gain pain relief.
      Patients are willing to accept greater additional risk of stomach bleed than
      heart attack/stroke. However, there exists considerable variation in risk-taking
      attitudes across patients. We recommend that clinicians examine the risk attitude
      and treatment preferences of each patient on an individual basis when deciding on
      a treatment regimen.

PMID- 17552040
TI  - Efficacy of tidal irrigation in Milwaukee shoulder syndrome.
AB  - OBJECTIVE: To assess the efficacy of tidal irrigation in patients with Milwaukee
      shoulder syndrome (MSS). METHODS: Ten patients with clinical diagnosis of MSS
      underwent ultrasound examination and tidal irrigation followed by instillation of
      methylprednisolone and tranexamic acid. A single shoulder was treated in 9 cases;
      in one patient with bilateral shoulder involvement, both shoulders were treated
      at different times. Six patients had longlasting disease (Group A) unsuccessfully
      treated with repeated joint fluid aspirations and intraarticular corticosteroid
      injections. Four patients had recent-onset illness without radiologic damage but
      with clinical findings similar to classic MSS (Group B), not previously treated
      with corticosteroid injections with symptoms dating from 3 months or less.
      Clinical examination including evaluation of adverse events, range of motion, and
      pain score by a 100 mm horizontal visual analog scale was scheduled just before
      tidal irrigation and after 2 and 6 months following the procedure in all cases.
      RESULTS: Short- and longterm safety was excellent in all patients. Group A
      patients experienced short-lived improvement so that tidal irrigation had to be
      repeated within 6 to 10 months. No further therapy was necessary in any of the
      Group B patients during a mean followup of 16.5 months (range 12-24) due to a
      persistent clinical improvement without clinically detectable joint effusion.
      CONCLUSION: Closed-needle joint irrigation is a minimally invasive procedure,
      which led to a significant improvement in both pain and active motion in patients
      with longstanding symptoms. Patients with recent-onset disease recovered
      completely.

PMID- 17552041
TI  - Influence of interleukin 10 promoter polymorphisms in susceptibility to giant
      cell arteritis in Northwestern Spain.
AB  - OBJECTIVE: Proinflammatory cytokines such as interferon-g (IFN-g) play an
      important role in the pathogenesis of giant cell arteritis (GCA). Interleukin 10
      (IL-10) is a Th2 cytokine with a suppressor effect on IFN-g production. We
      assessed the influence of functional IL-10 gene promoter polymorphisms in
      susceptibility to GCA in individuals from Northwestern Spain. METHODS: One
      hundred three patients with biopsy-proven GCA and 226 matched controls from the
      Lugo region of Northwest Spain were genotyped for IL-10 -1082 G/A (rs1800896) and
      -592 C/A (rs1800872) promoter single nucleotide polymorphisms (SNP) by Taqman 5'
      allelic discrimination assay using Taqman predesigned SNP genotyping assays
      (numbers C_1747360_10 and C_1747363_10, respectively). RESULTS: A significant
      difference in the distribution of -1082 G/A genotypes between GCA patients and
      controls was observed (p = 0.034). It was mainly due to a decreased number of GCA
      patients carrying the -1082 A/A genotype (23.3%) compared with controls (36.7%)
      [p = 0.01, corrected p (pc) = 0.03; OR 0.53, 95% CI 0.31- 0.90]. In addition,
      haplotype analysis showed that the ATA haplotype frequency was slightly decreased
      (p = 0.05, pc = 0.2; OR 0.6, 95% CI 0.4-1.0), whereas the uncommon GTA haplotype
      was significantly increased in GCA patients compared with controls (p = 0.00005,
      pc = 0.0002; OR 8.7, 95% CI 2.2-34.8). CONCLUSION Our results suggest a potential
      implication of IL-10 -1082 promoter polymorphism in susceptibility to GCA in
      Northwestern Spain.

PMID- 17552042
TI  - A review of the sapporo and revised Sapporo criteria for the classification of
      antiphospholipid syndrome. Where do the revised sapporo criteria add value?
AB  - OBJECTIVE: The preliminary classification criteria for antiphospholipid syndrome
      (APS), or the Sapporo criteria, are widely used for the inclusion of patients
      with APS into clinical studies. Revised Sapporo criteria have been proposed as an
      improved criteria set. Whether these criteria sets fulfill the current standards
      of measurement science are unknown. The purpose of this study was (1) to evaluate
      the developmental methodology and measurement properties of the Sapporo and the
      revised Sapporo criteria for use in clinical trials; and (2) to evaluate if the
      revised Sapporo criteria provide added value over the Sapporo criteria. METHODS:
      A computer search for articles describing use of the Sapporo and the revised
      Sapporo criteria was performed. Item generation, item reduction, sensibility,
      validity, and reliability of the criteria were evaluated. RESULTS: The Sapporo
      criteria set has incremental face and content validity over its predecessors.
      However, through separation of anti-ss2-glycoprotein I antibodies as a sub-item,
      the specification of a wider time interval between serologic testing, the
      specification of a time interval between serology and clinical manifestations,
      and specification of definitions for clinical manifestations and laboratory titer
      thresholds, the revised Sapporo criteria set has incremental face and content
      validity over the Sapporo criteria. The complexity of the criteria, diagnostic
      tests, and immunologic tests limits their feasibility. The reliability of each
      criterion is unknown. The discriminative capacity of the Sapporo criteria is
      good, with sensitivity, specificity, and positive and negative predictive values
      of 0.71, 0.98, 0.95, and 0.88, respectively, compared to patients with systemic
      lupus erythematosus. The discriminative capacity of the revised Sapporo criteria
      is unknown. CONCLUSION: The revised Sapporo criteria set has incremental face and
      content validity compared its predecessors. Reliability testing of each criterion
      is needed before these criteria can be confidently used in multicenter APS
      trials. Discriminatory testing of the revised Sapporo criteria is required.

PMID- 17552043
TI  - Thrombocytosis in systemic lupus erythematosus: a possible clue to
      autosplenectomy?
AB  - OBJECTIVE: Thrombocytosis can be due to a myeloproliferative disorder or to a
      reactive or secondary process; among these are connective tissue disorders, in
      particular systemic lupus erythematosus (SLE). Besides being an expression of
      active disease, this unusual finding has also been described in SLE complicated
      by autosplenectomy. We evaluated the prevalence of thrombocytosis in a series of
      SLE patients and its relationship to functional asplenia. METHODS: Platelet count
      was evaluated in 465 consecutive Caucasian patients with SLE (387 women, 78 men,
      median age 54 yrs). Thrombocytosis was defined as platelet count > 400 x 10(9)/l
      in at least 3 blood samples. All patients with thrombocytosis underwent
      peripheral blood smears for erythrocyte abnormalities and instrumental spleen
      evaluation. RESULTS: Seventeen patients (3.7%) with thrombocytosis were observed.
      Peripheral blood smear showed Howell-Jolly bodies, spherocytes, and target cells
      in 3/17 patients (17.6%). In the same 3 patients, ultrasound and computed
      tomography failed to evidence the spleen, and liver-spleen scans showed absence
      of splenic uptake (a finding indicative of functional autosplenectomy). One
      satisfied criteria for antiphospholipid syndrome (APS), and the other 2 patients
      had positive IgG antiphospholipid antibodies (aPL) at medium titer. CONCLUSION:
      The sudden appearance and persistence of thrombocytosis or even the apparent
      reversal of thrombocytopenia in patients with SLE should raise suspicion of
      autosplenectomy, in particular if secondary APS or aPL is present.

PMID- 17552044
TI  - The association of race and ethnicity with disease expression in male US veterans
      with rheumatoid arthritis.
AB  - OBJECTIVE: To examine the association of race/ethnicity with measures of disease
      activity and severity among male US veterans with rheumatoid arthritis (RA).
      METHODS: Measures of disease activity and severity were examined in a group of US
      veterans (n = 573) with RA, comparing measures in African American men (n = 79)
      with Caucasian men (n = 494). Dichotomous variables were compared using logistic
      regression while continuous variables were examined using linear regression,
      adjusting for the effects of age, disease duration, and smoking status. RESULTS:
      Compared to Caucasians, African Americans were slightly younger (65.0 vs 67.1
      yrs; p = 0.09) at enrollment and had a similar age at disease onset (50.5 vs 50.6
      years; p = 0.98). After adjusting for age, disease duration, and smoking status,
      there were no differences based on race/ethnicity in rheumatoid factor
      positivity, the presence of radiographic changes, physical functioning, swollen
      joint counts, Disease Activity Score (DAS28), or global well-being scores. In
      contrast, African Americans were about 50% less likely than Caucasians with RA to
      have subcutaneous nodules (adjusted OR 0.51, 95% CI 0.30-0.86) and had lower
      tender joint counts (p = 0.007), associations that were attenuated and not
      significant with further adjustment for collection site. CONCLUSION: With the
      possible exception of lower rates of rheumatoid nodules and lower tender joint
      counts in African Americans, there is little evidence to support the existence of
      important racial/ethnic differences in RA disease expression between African
      American and Caucasian men.

PMID- 17552045
TI  - Health status disparities in ethnic minority patients with rheumatoid arthritis:
      a cross-sectional study.
AB  - OBJECTIVE: To examine disparities in disability, pain, and global health between
      Caucasian (n = 4294) and African American (n = 283) and Caucasian and Hispanic (n
      = 153) patients with rheumatoid arthritis (RA). METHODS: Patients were from 9
      Arthritis, Rheumatism, and Aging Medical Information System databanks. Cross
      sectional data were derived from the Health Assessment Questionnaire. Staged
      multivariate analysis of covariance was used to explore roles of possible
      contributing factors (age, sex, education, disease duration, number of comorbid
      conditions, and treatment) to ethnic minority disparities. RESULTS: The cohort
      was 91% Caucasian and 76% female. Caucasians were significantly older than
      African Americans and Hispanics (62 vs 56 and 55 yrs; both p < 0.0001 from
      Caucasians), better educated (13 vs 12 and 12 yrs; both p < 0.0001 from
      Caucasians), and had their RA longer (16 vs 13 and 15 yrs; p < 0.01 for African
      Americans). Unadjusted disability scores were statistically indistinguishable,
      but pain was worse in both ethnic groups (p < 0.01), and global health worse in
      Hispanics (p < 0.05). After adjustment for covariates, African Americans had the
      poorest outcomes in all 3 measures, although only pain in African Americans (p <
      0.05) was statistically different from Caucasians. CONCLUSION: Results of this
      exploratory study suggest that in a relatively similar cohort of patients with
      RA, minority health disparities exist. Both ethnic groups had poorer outcomes for
      all 3 measures than Caucasians after adjustment. Additional study and
      longitudinal research with larger numbers of patients are needed to improve our
      understanding of these differences and to assess potential causal roles.

PMID- 17552046
TI  - Effects of high-dose atorvastatin on antiinflammatory properties of high density
      lipoprotein in patients with rheumatoid arthritis: a pilot study.
AB  - OBJECTIVE: Patients with rheumatoid arthritis (RA) have a 2-3-fold increased risk
      of myocardial infarction. Recent work suggests that plasma high density
      lipoproteins (HDL) from patients with RA are more proinflammatory than HDL from
      controls. We examined the effects of atorvastatin 80 mg daily on the inflammatory
      properties of HDL and clinical disease activity in RA. METHODS: Twenty subjects
      with active RA (mean Disease Activity Score 5.13 +/- 0.92) without dyslipidemia
      and no history of coronary artery disease were randomized in a double-blind
      placebo-controlled trial to receive 80 mg of atorvastatin (A) or placebo (P)
      daily in addition to stable antirheumatic drug therapy. Disease activity
      variables were followed over 12 weeks and the anti-/proinflammatory properties of
      HDL were determined by a cell-free assay (CFA) that measures lipid oxidation
      products. RESULTS: After 12 weeks, subjects completing the A protocol had a mean
      reduction in CFA values of 14.8 +/- 21.7%, while subjects completing P protocol
      had a mean increase in CFA values of 7.1 +/- 13.2% (p = 0.026). There was a trend
      for a decrease in highly sensitive C-reactive protein (hs-CRP) over 12 weeks in
      the A group compared to an increase in hs-CRP in the P group (p > 0.05), but
      changes in measures of clinical disease activity and plasma
      cytokine/intercellular adhesion molecule-1 levels were not significantly
      different in the A and P groups. CONCLUSION: In patients with active RA, HDL was
      rendered more antiinflammatory by high-dose atorvastatin compared to placebo.
      Functional characterization of HDL may warrant further investigation as a method
      of cardiovascular risk assessment in RA patients without traditional coronary
      risk factors. (ClinicalTrials.gov number NCT00356473).

PMID- 17552047
TI  - Variability in the use of orthopedic surgery in patients with rheumatoid
      arthritis in Spain.
AB  - OBJECTIVE: To analyze sociodemographic and clinic-associated factors of patients
      with rheumatoid arthritis (RA) undergoing any orthopedic surgery (AOS) and total
      joint replacement (TJR) in Spain. METHODS: A retrospective medical record review
      was performed in a probabilistic sample of 1379 RA patients from 46 centers
      distributed in 16 of 19 regions in Spain. Sociodemographic and clinical features,
      use of drugs, and arthritis-related joint surgeries were recorded following a
      standardized protocol. Gross domestic product (GDP) data were obtained from the
      National Statistical Index. RESULTS: Of 1379 patients, a total of 358 (26%)
      underwent one or more joint surgeries, and 194 (14%) had a TJR. The median time
      to first orthopedic procedure was 12.5 years from presentation of RA and the
      estimated rate was 5.6 surgeries per 100 person-years. The rate of AOS was
      increased in women, patients with RA with extraarticular complications, with
      longterm RA (> 10 yrs), with functional grade III-IV, and with persistent
      inflammatory disease. The risk factors for undergoing a TJR were longterm RA,
      functional grade III-IV, and extraarticular complications. Patients from regions
      with higher GDP per capita were more likely to undergo a procedure. CONCLUSION:
      Clinical variables reflecting disease activity and severity are predictors of
      orthopedic surgery, but geographic and socioeconomic variables were also
      independently associated with the rate of orthopedic surgery.

PMID- 17552048
TI  - Changes in biomarkers of inflammation and bone turnover and associations with
      clinical efficacy following infliximab plus methotrexate therapy in patients with
      early rheumatoid arthritis.
AB  - OBJECTIVE: To determine if changes in biomarkers of inflammation and bone
      turnover in response to treatment with infliximab plus methotrexate (MTX) versus
      MTX alone are associated with improvement in clinical measures of signs,
      symptoms, and structural damage in early rheumatoid arthritis. METHODS: Sera were
      collected from patients in the ASPIRE study who received 3 mg/kg (n = 48) or 6
      mg/kg infliximab plus MTX (n = 55), or MTX alone (n = 41). Several baseline
      biomarker levels correlated with changes in median percentage of American College
      of Rheumatology improvement (ACR-N), 50% improvement in ACR response (ACR50), and
      van der Heijde-modified Sharp score (vdHSS) at Week 54. RESULTS: Infliximab plus
      MTX treatment resulted in more rapid decreases in levels of matrix
      metalloproteinase-3 (MMP-3), intercellular cell adhesion molecule-1, interleukin
      8 (IL-8), and tumor necrosis factor-a than treatment with MTX alone. Baseline
      levels and decreases from baseline to Weeks 6 and 54 in MMP-3 correlated with
      improvement in ACR-N response at Week 54. An increase in IL-8 levels from
      baseline to Week 54 correlated with worsening in vdHSS at Week 54 in the MTX
      alone group. Regression analysis of markers at baseline showed that MMP-3 was the
      only variable associated with ACR50 response and less worsening in vdHSS at Week
      54. CONCLUSION: Treatment with infliximab plus MTX resulted in a rapid decrease
      in inflammation markers. MMP-3 levels at different timepoints were consistently
      associated with clinical improvements at Week 54 in the infliximab plus MTX
      group, while increases in IL-8 levels correlated with a worsening in vdHSS at
      Week 54 in the MTX-alone group.

PMID- 17552049
TI  - Autoantibodies: innocent bystander or key player in immunosenescence and
      atherosclerosis?

PMID- 17552050
TI  - Clinical anatomy: an unmet agenda in rheumatology training.

PMID- 17552051
TI  - Patient joint counts in rheumatoid arthritis--"cents-ible or cents-less?".

PMID- 17552052
TI  - Rheumatoid arthritis and participation--the social animal revisited.

PMID- 17552053
TI  - Dactylitis or "sausage-shaped" digit.

PMID- 17552054
TI  - The Academic Medical Center Linear Disability Score item bank: psychometric
      properties of a new generic disability measure in rheumatoid arthritis.
AB  - OBJECTIVE: To determine the psychometric properties of the Academic Medical
      Center (AMC) Linear Disability Scale (ALDS) item bank in a population of patients
      with rheumatoid arthritis (RA). METHODS: 129 patients with RA completed the ALDS
      and Health Assessment Questionnaire Disability Index (HAQ-DI) at baseline, and
      after 8 and 16 weeks of anti-tumor necrosis factor-alpha treatment. Disease
      activity assessments at these timepoints included serum levels of C-reactive
      protein, Disease Activity Score 28, morning stiffness, and visual analog scales
      for global disease activity and fatigue. RESULTS: Reliability of the ALDS was
      excellent (homogeneity, Cronbach's alpha = 0.95; test-retest, intraclass
      correlation coefficient = 0.93). The ALDS results at baseline were strongly
      correlated with the HAQ-DI (r = -0.75). With regard to known group validity, both
      instruments discriminated between higher and lower disease activity (ALDS, p <
      0.0001; HAQ-DI, p = 0.002) and between non-, moderate, and good responders (ALDS,
      p = 0.002; HAQ-DI, p < 0.0001), indicating that both instruments differentiate
      between groups. The ALDS was moderately to highly responsive to changes between
      baseline and after 8 weeks and 16 weeks of treatment (standardized response mean,
      range = 0.71-1.19). No substantial floor or ceiling effects were found.
      CONCLUSION: Our results show that the ALDS is a promising new instrument, with at
      least equivalent psychometric properties compared to the HAQ-DI. Advantages of
      the ALDS item bank are its linear structure and an item bank that can be adapted
      depending on the ability level of the patient.

PMID- 17552055
TI  - Mannose-binding lectin and susceptibility to infection in Chinese patients with
      systemic lupus erythematosus.
AB  - OBJECTIVE: To test the hypothesis that low serum mannose-binding lectin (MBL)
      levels, as a result of the single-nucleotide polymorphisms in the promoter region
      (-221 X/Y) and exon 1 (codon 54 A/B) of the MBL2 gene, predispose to infection in
      Chinese patients with systemic lupus erythematosus (SLE). METHODS: Two hundred
      forty-five patients with SLE were prospectively followed for the development of
      major infective episodes that required hospitalization and antibiotic treatment
      during 1992-2005. MBL genotypes were determined by polymerase chain reaction and
      serum MBL levels were measured by ELISA. RESULTS: In total, 254 major infections
      developed in 130 patients. Serum MBL levels were shown to correlate inversely
      with the number of bacterial infections (r = -0.13, p = 0.03). The distribution
      of MBL genotypes was similar in patients with and without major infection (p =
      0.84). Patients with major infection also had more major lupus exacerbations that
      required daily prednisolone dose > or = 15 mg. Logistic regression showed that
      log MBL level (odds ratio 0.516, 95% confidence interval 0.305-0.873; p = 0.01)
      and major lupus exacerbation (OR 1.382, 95% CI 1.154-1.654; p < 0.001) were
      independent risk factors to major bacterial infection after adjustment for age
      and disease duration. Multiple regression analysis showed an increase in risk of
      bacterial infection by 34.2% for every decrease in serum MBL level by one log,
      and by 22.8% for each increase in number of major lupus exacerbations.
      CONCLUSION: Low serum MBL level predisposes Chinese patients with SLE to more
      major infections, in particular bacterial ones.

PMID- 17552056
TI  - Differential expression of Ro/SSA 60 kDa and La/SSB, but not Ro/SSA 52 kDa, mRNA
      and protein in minor salivary glands from patients with primary Sjogren's
      syndrome.
AB  - OBJECTIVE: To analyze the protein and messenger RNA (mRNA) expression of La/SSB,
      Ro/SSA 60, and Ro/SSA 52 antigens in minor salivary glands (MSG) from patients
      with primary Sjogren's syndrome (pSS). METHODS: La/SSB, Ro/SSA 60, and Ro/SSA 52
      protein expression was studied by immunohistochemistry in MSG from 26 patients
      with pSS and 16 controls. mRNA expression was determined by real-time polymerase
      chain reaction in MSG of 10 patients with pSS and 7 controls. RESULTS: La/SSB and
      Ro/SSA 60, but not Ro/SSA 52, mRNA expression was higher in samples from patients
      with pSS compared to controls (p < 0.05). La/SSB protein had higher expression in
      the cytoplasm of ductal cells than in the cytoplasm of mucous acinar cells in
      patients with pSS (p = 0.013) but not in controls. Ro/SSA 60 had higher
      expression in the cytoplasm of ductal cells than in the cytoplasm of serous
      acinar cells in patients with pSS (p = 0.006) but not in controls. The Ro/SSA 52
      expression pattern was similar in patients and controls. There was no association
      between circulating autoantibodies to Ro/SSA or La/SSB and the aberrant
      expression of the cognate autoantigens. CONCLUSION: The increased Ro/SSA 60 and
      La/SSB mRNA expression in MSG of patients with pSS as well as the differential
      Ro/SSA 60 and La/SSB protein expression in ductal cells of MSG in patients with
      pSS suggest that these these 2 autoantigens, but not Ro/SSA 52, are probably
      involved in triggering and maintaining the tissue-specific autoimmune response in
      pSS MSG and may contribute to the antigen-driven immune response and local
      autoantibody production in pSS.

PMID- 17552057
TI  - Cystatin C binds serum amyloid A, downregulating its cytokine-generating
      properties.
AB  - OBJECTIVE: To assess the interaction between cystatin C (CysC) and serum amyloid
      A protein (SAA). METHODS: Levels of CysC and SAA and antibodies against these
      proteins were assessed in the paired blood and synovial fluid (SF) samples of 90
      patients with rheumatoid arthritis (RA). Age and sex matched individuals having
      normal iohexol clearance (n = 90) and SF following joint trauma (n = 40) were
      used as controls. In vitro experiments included assessment of interaction between
      CysC and SAA by ELISA and the influence of CysC on SAA functions. RESULTS: A
      pilot screening for cystatins C, E, and F in blood and SF of patients with RA
      found CysC to be by far the predominant extracellular cystatin. Circulating CysC
      levels were significantly lower in patients with RA compared to the matched
      controls (0.81 +/- 0.03 vs 1.01 +/- 0.03 mg/l; p = 0.05). These low CysC levels
      could not be explained by the presence of anti-CysC antibodies in patients with
      RA. In contrast, concentrations of CysC that accumulated in the inflamed SF were
      significantly greater in patients with erosive RA (1.66 +/- 0.08 mg/l) compared
      to nonerosive RA (1.36 +/- 0.06 mg/l; p = 0.003) and controls (1.18 +/- 0.03
      mg/l; p = 0.043). In vitro studies showed direct binding of CysC to SAA. CysC/SAA
      binding impaired proinflammatory effects of SAA, reducing its ability to trigger
      expression of proinflammatory cytokines. CONCLUSION: Our study shows a relative
      deficiency of circulating CysC during systemic inflammation in RA. Physical
      interaction between CysC and the acute-phase protein SAA (1) provides an
      explanation for CysC deficiency; and (2) suggests that CysC is regulating
      inflammatory responses. We hypothesize that decreased systemic CysC levels
      predispose to accelerated atherosclerosis and development of amyloidosis in
      patients with RA.

PMID- 17552058
TI  - Decision rules for selecting women for bone mineral density testing: application
      in postmenopausal women referred to a bone densitometry unit.
AB  - OBJECTIVE: Although several decision rules have been developed to identify
      postmenopausal women who may be selected for dual-energy x-ray absorptiometry
      measurements, information on their utility in a clinical setting is scarce. We
      evaluated the utility of 4 previously validated decision rules in a large group
      of Spanish postmenopausal women referred to a bone densitometry unit. METHODS: We
      reviewed the data on 665 postmenopausal women (mean age 54.2 +/- 5.4 yrs). We
      selected the 4 decision rules that could be applied with the information that was
      available: the Osteoporosis Risk Assessment Instrument (ORAI), Osteoporosis Self
      Assessment Tool (OST), Osteoporosis Index of Risk (OSIRIS), and Body Weight
      Criterion (BWC). The sensitivity, specificity, and predictive values of each
      decision rule were determined. RESULTS: The ORAI would recommend 45% of women for
      bone mineral density (BMD) testing, OST 46%, OSIRIS 37%, and BWC 70%. Sensitivity
      values obtained in the overall series were 64.1% for the ORAI, 69.2% for OST,
      58.1% for OSIRIS, and 83.8% for BWC. The sensitivity increased progressively with
      age. The negative predictive value in the overall series was 88.5% for ORAI,
      89.9% for OST, 88.4% for OSIRIS, and 90.6% for BWC. CONCLUSION: In a
      complementary way with previous studies in older women, where decision rules were
      valuable to identify the majority of women likely to have osteoporosis, our data
      indicate that in younger postmenopausal women, decision rules are useful as a
      screening method to rule out the presence of osteoporosis and the need for BMD
      scanning.

PMID- 17552059
TI  - Intrinsic muscle spasm of the hand; Bunnell's sign.

PMID- 17552060
TI  - Effective etanercept treatment for psoriatic arthritis complicating concomitant
      human immunodeficiency virus and hepatitis C virus infection.
AB  - High levels of tumor necrosis factor-alpha (TNF-alpha) are associated with
      hepatitis C virus (HCV) infection and all stages of human immunodeficiency virus
      (HIV) infection. TNF-alpha may have a role in both the pathogenesis and the
      response to treatment of these chronic viral diseases. We describe a 42-year-old
      HIV/HCV coinfected hemophiliac man who developed psoriasis and severe psoriatic
      arthritis not responding to combination treatment with methotrexate and
      cyclosporin A. Treatment with etanercept 25 mg twice weekly was followed by
      remission of the joint inflammation and improvement of the exanthem. This is the
      first report of anti-TNF-alpha treatment for rheumatic complications in a patient
      with both HIV and HCV infection.

PMID- 17552061
TI  - Severe hemophilic arthropathy of the elbow and knee.

PMID- 17552062
TI  - The future of damage assessment in vasculitis.
AB  - Damage denotes the aspects of chronic disease that do not reverse with therapy.
      This concept is particularly important for the primary systemic vasculitides,
      since the careful differentiation between activity and damage may help avoid
      unnecessary exposure to cytotoxic medications. Damage significantly influences
      both longterm prognosis and quality of life. Because the primary systemic
      vasculitides have diverse manifestations, the use of a damage assessment
      instrument is crucial to ensure reproducibility. The Vasculitis Damage Index
      (VDI) is the only validated measure for damage assessment in vasculitis. Use of
      the VDI in recent clinical trials has shown that it may not adequately determine
      the full spectrum of damage experienced by patients with vasculitis of small- and
      medium-size vessels. We propose reexamining the way in which damage is assessed,
      focusing on vasculitides of small- and medium-size vessels, and outline an
      initiative to create a substantially revised and improved damage assessment
      instrument using data-driven approaches. This initiative is part of a larger
      international effort to create a unified approach to disease assessment for the
      primary systemic vasculitides.

PMID- 17552063
TI  - Worker productivity outcome measures in arthritis.
AB  - Arthritis is a leading cause of work disability and makes up a significant amount
      of the socioeconomic cost and health burden to the working age population. We
      discuss the measurement of worker productivity: that is, absenteeism and
      presenteeism. Absenteeism refers to the time missed from work due to health
      reasons and presenteeism refers to the time of impaired performance while at work
      due to health reasons resulting in productivity loss. While the term absenteeism
      is commonly used and has several definitions by itself, the current arthritis
      literature lacks the use of presenteeism as a work outcome measure in describing
      health states of the workers and for economic costing. Due to advanced medical
      management and job accommodations that allow workers to stay at work, absenteeism
      alone may not be enough to give us a complete picture of worker productivity.
      From our review, we found that the conceptualization and measurement of
      absenteeism and presenteeism differ. Our research agenda was to carry forward a
      work outcome measurement that can be used for cost calculation and that can
      determine levels or states of productivity loss so we can accurately measure the
      influence of arthritis and advance arthritis care. We recognize the need to
      perform psychometric testing of work outcome measures and to improve our ability
      to identify transitions (i.e., move in and out of a productivity state over time)
      made by workers with arthritis.

PMID- 17552064
TI  - Outcome evaluations in gout.
AB  - Methods to measure outcomes in gout still require consensus and validation. This
      Special Interest Group was assembled to identify domains of interest and is now
      evaluating a series of outcomes for features of acute gouty arthritis and chronic
      gout. To accomplish this, working groups have been formed and domains identified.
      Delphi methodology has been used to address gouty flares as an outcome of
      greatest interest. Studies addressing other outcome measures were reported at the
      OMERACT 8 meeting and validation has begun on some outcomes. There has been
      progress on developing a definition of a flare, and validating reproducibility of
      some chronic gout outcome measures in some domains, such as tophus size and
      patient perceptions. Use of these outcomes as well as a health-related quality of
      life measure are being studied in clinical trials. Pain on a Likert scale appears
      to be a valid outcome in acute gout. Final validation of these outcomes has not
      yet been achieved. In summary, the unique problems of evaluating outcomes in gout
      are finally being addressed. While no measures are available for use yet, an
      agenda has been developed.

PMID- 17552065
TI  - Preliminary development of a responder index for chronic low back pain.
AB  - OBJECTIVE: One of the greatest obstacles to identifying the most effective
      therapy for chronic low back pain (CLBP) is the lack of standardized outcome
      measures for assessing treatment effect in clinical trials. The aim of the
      OMERACT Special Interest Group was to discuss the development and validation of a
      preliminary responder index in CLBP. METHODS: Patient data from 5 clinical trials
      of celecoxib and valdecoxib use in CLBP were used to assess the reliability and
      validity of multiple items in the outcome domains of pain, functioning, and
      overall impression of health. Candidate preliminary responder indices were
      selected on the basis of effect size, high chi-square test values, and a placebo
      response rate < or = 25%. RESULTS: Candidate indices comprised improvements in
      single outcome measures and combinations of improvements and/or avoidance of
      worsening in multiple measures. The preliminary choice for the responder index
      was at least 30% improvement in pain, with an improvement of at least 30% in
      patient global assessment and no worsening in function. CONCLUSION: Further
      studies are needed to refine a responder index for CLBP trials that is clinically
      relevant, reliable, and easy to administer for standardizing assessments across
      clinical trials.

PMID- 17552066
TI  - Development of the effective musculoskeletal consumer scale.
AB  - Programs and initiatives have been created to empower, educate, and provide
      information to consumers; these are sometimes generically known as self
      management interventions. Evaluating and comparing such programs has been a
      challenge, as many skills that consumers believe are important to manage and
      participate in their individual healthcare are not currently captured by existing
      tools. The objective of the Effective Musculoskeletal Consumer Project is to
      develop a scale to measure an effective consumer. A review of the literature,
      interviews, workshops, and preliminary surveys at OMERACT 7 (May 2005) were
      conducted in the first phases of the Project. A questionnaire consisting of 64
      items was developed to measure the skills and attributes of an effective
      musculoskeletal (MSK) consumer. Content experts on our team reduced this scale to
      48 items, which was pilot-tested with consumers from Canada and Australia.
      Dimensionality assessment showed that the scale was unidimensional. Classical and
      item response theory analyses showed that the 48-item scale had quite high
      reliability, but that 2 items were very poor. Based on the item analysis, 35
      items were retained. The revised scale was presented at OMERACT 8, where a panel
      reviewed the scale and provided input. This input and another expert review by
      our team was used to further refine the Effective Consumer Scale to 17 items.
      Plans are now under way to validate this 17-item scale in self-management
      interventions.

PMID- 17552067
TI  - Standardizing assessment and reporting of adverse effects in rheumatology
      clinical trials II: the Rheumatology Common Toxicity Criteria v.2.0.
AB  - OBJECTIVE: The OMERACT Drug Safety Working Group focuses on standardization of
      assessment and reporting of adverse events in clinical trials and longitudinal
      and observational studies in rheumatology. This group developed the Rheumatology
      Common Toxicity Criteria (RCTC) in 1999, building on the Oncology Common Toxicity
      Criteria. At OMERACT 8, a workshop group reviewed the use of the RCTC and other
      instruments in rheumatology clinical trials to date, to revise and to stimulate
      its implementation. METHODS: The Working Group drafted a revision of the RCTC
      after an iterative examination of its contents, terms, and definitions. The RCTC
      were compared with the Oncology Common Toxicity Criteria (CTC v.2.0), and the
      Common Terminology Criteria for Adverse Events (CTCAE v.3.0). In addition a
      pharmaceutical company focus group met to clarify the challenges of application
      of RCTC terms and definitions, relative to the standard in pharmaceutical
      clinical trials, i.e., verbatim recording of adverse events followed by mapping
      to Medical Dictionary of Drug Regulatory Activities (MedDRA) terms. The workshop
      focused on the proposed revision of RCTC to version 2.0 and on the research
      agenda, including a validation of the RCTC in future trials. RESULTS: At OMERACT
      8, breakout groups amended the contents of the 4 current and 2 new categories of
      adverse event terms within the draft RCTC v.2.0. Participants recognized the need
      to standardize the definitions for disease flares, infection, malignancy, and
      certain syndromes such as drug hypersensitivity and infusion reactions. Moderate
      consensus (62%) was reached in the final plenary session that the amended RCTC
      v.2.0 should be promulgated and tested in available trials of anti-tumor necrosis
      factor agents. CONCLUSION: The RCTC has face validity and construct validity.
      However, documentation of discrimination and feasibility (the other elements of
      the OMERACT filter) is needed. Collaboration with drug safety working groups in
      rheumatology professional organizations is necessary to enable this project.

PMID- 17552068
TI  - Fibromyalgia syndrome.
AB  - The fibromyalgia syndrome (FM) workshop at OMERACT 8 continued the work initiated
      in the first FM workshop at OMERACT 7 in 2004. The principal objectives were to
      work toward consensus on core domains for assessment in FM studies, evaluate the
      performance quality of outcome measures used in a review of recent trials in FM,
      and discuss the research agenda of the FM working group. An initiative to include
      the patient perspective on identification and prioritization of domains,
      consisting of focus groups and a patient Delphi exercise, was completed prior to
      OMERACT 8. Patient-identified domains were, for the most part, similar to those
      identified by clinician-investigators in terms of symptoms and relative
      importance. However, patients identified certain domains, such as stiffness, that
      were not included by physicians, and emphasized the importance of domains such as
      dyscognition and impaired motivation. Many of the principal domains agreed upon
      by the clinician-investigators, patients, and OMERACT participants, including
      pain, fatigue, sleep, mood, and global measures, have been used in clinical
      trials and performed well when viewed through the OMERACT filter. The research
      agenda items reviewed and approved for continued study included development of
      objective "biomarkers" in FM, development of a responder index for FM, and
      coordination with the WHO's International Classification of Functioning
      Disability and Health (ICF) Research Branch and the US National Institutes of
      Health's Patient Reported Outcome Measures Information System network (PROMIS) to
      develop improved measures of function, quality of life, and participation. The
      OMERACT process has provided a framework for identification of key domains to be
      assessed and a path toward validation and standardization of outcome measures for
      clinical trials in FM.

PMID- 17552069
TI  - Improving patient reported outcomes using item response theory and computerized
      adaptive testing.
AB  - OBJECTIVE: Patient reported outcomes (PRO) are considered central outcome
      measures for both clinical trials and observational studies in rheumatology. More
      sophisticated statistical models, including item response theory (IRT) and
      computerized adaptive testing (CAT), will enable critical evaluation and
      reconstruction of currently utilized PRO instruments to improve measurement
      precision while reducing item burden on the individual patient. METHODS: We
      developed a domain hierarchy encompassing the latent trait of physical
      function/disability from the more general to most specific. Items collected from
      165 English-language instruments were evaluated by a structured process including
      trained raters, modified Delphi expert consensus, and then patient evaluation.
      Each item in the refined data bank will undergo extensive analysis using IRT to
      evaluate response functions and measurement precision. CAT will allow for real
      time questionnaires of potentially smaller numbers of questions tailored directly
      to each individual's level of physical function. RESULTS: Physical
      function/disability domain comprises 4 subdomains: upper extremity, trunk, lower
      extremity, and complex activities. Expert and patient review led to consensus
      favoring use of present-tense "capability" questions using a 4- or 5-item Likert
      response construct over past-tense "performance"items. Floor and ceiling effects,
      attribution of disability, and standardization of response categories were also
      addressed. CONCLUSION: By applying statistical techniques of IRT through use of
      CAT, existing PRO instruments may be improved to reduce questionnaire burden on
      the individual patients while increasing measurement precision that may
      ultimately lead to reduced sample size requirements for costly clinical trials.

PMID- 17552070
TI  - OMERACT/OARSI initiative to define states of severity and indication for joint
      replacement in hip and knee osteoarthritis.
AB  - OBJECTIVE: Time to theoretical indication of joint replacement surgery has been
      proposed as a primary outcome for potential structure-modifying interventions for
      osteoarthritis (OA). The objectives of this OMERACT/OARSI Working Group were to
      identify pain, physical function, and structure states that represent the
      progression from early to late disease for individuals with OA of the hip and
      knee, and to create a composite measure of these 3 domains to define states of OA
      severity and a surrogate measure of "need for joint replacement surgery."
      METHODS: For pain, focus groups and one-on-one interviews were used. For
      function, Rasch analysis was performed on existing indices the Hip Dysfunction
      and Osteoarthritis Outcome Score (HOOS) and the Knee injury and Osteoarthritis
      Outcome Score (KOOS), each of which subsumes the Western Ontario and McMaster
      University Osteoarthritis Index (WOMAC) questions. For structure, a comparison of
      existing indices (Kellgren-Lawrence, OARSI stages, and joint space width) was
      performed for the hip and the knee. RESULTS: For pain, key features of pain that
      are most distressing to people with OA from early to late disease were
      identified. For function, the reduction of the number of items based on the
      existing indices continues. For structure, the analysis is also ongoing.
      CONCLUSION: Preliminary results were presented at OMERACT 8; the final objective
      will be to combine the 3 domains (pain, function, and structure) and to create a
      composite index that could define states of severity and "need for total joint
      replacement," which could be used to evaluate treatment response to disease
      modifying drugs in OA clinical trials.

PMID- 17552071
TI  - Costs of rheumatoid arthritis in Hungary.

PMID- 17552072
TI  - Prevention. Illinois health care plan could help to stop HIV/AIDS spread in U.S.

PMID- 17552073
TI  - Confinement. Freedom denied  HIV-positive man in mental health dispute.

PMID- 17552074
TI  - HIV and TB. WHO: drug resistance and HIV threaten anti-TB drive.

PMID- 17552075
TI  - Discrimination. Equitable tolling denied man fired for being HIV-positive.

PMID- 17552077
TI  - Sentencing. Despondency claim over false-positive HIV test fails.

PMID- 17552076
TI  - Prisons. HIV-positive man denied free counsel over health care claim.

PMID- 17552080
TI  - Spotlight: Giuseppe Mancia, MD, PhD. Interview by Emma Baines.

PMID- 17552079
TI  - Prevention of depression in children and adolescents.

PMID- 17552081
TI  - History of cardiology: Desmond Julian, MD.

PMID- 17552082
TI  - [Two year use of Telzir: what are the perspectives?].

PMID- 17552083
TI  - Whipple of the Whipple operation.

PMID- 17552084
TI  - Time 100 scientists & thinkers. Tullis Onstott.

PMID- 17552085
TI  - Treating hyponatremia in heart failure.
AB  - Hyponatremia is common and associated with adverse outcomes in patients with
      congestive heart failure (CHF). In many patients who have CHF with hyponatremia,
      plasma arginine vasopressin (AVP) is elevated inappropriately. AVP causes water
      retention by interacting with V2 receptors in the renal collecting duct, leading
      to dilutional hyponatremia and increased ventricular preload. AVP also may
      contribute to pathophysiologic process in CHF by interacting with V(IA) receptors
      on vascular smooth muscle cells and myocytes. The potential utility of AVP
      antagonists--V2 antagonists and dual V(IA)/V2 antagonists--in correcting
      hyponatremia and relieving the congestion and edema associated with CHF is being
      actively explored. Combined antagonists may offer additional benefit by
      interfering with excessive V(IA) signaling. Unlike diuretics, which increase
      urine volume and electrolyte excretion, AVP antagonists of these types produce an
      aquaresis characterized by an increase in free water clearance concomitant with
      sparing of electrolytes. Studies in experimental CHF as well as preliminary
      clinical trials with selective and nonselective V2 antagonists have been
      encouraging, suggesting that these agents may hold promise for treatment of
      hyponatremia in CHF.

PMID- 17552086
TI  - [Oral health care and health decentralization in Brazil: two case studies in
      Bahia State].
AB  - A comparative case study was performed in two selected municipalities in the
      State of Bahia, Brazil, to discuss the relationship between health system
      decentralization and characteristics of oral health services. A logical model was
      developed and submitted to an expert panel. Data were gathered through in-depth
      interviews, field observation, and analysis of secondary data from the national
      Health System database. The results point to the influence of municipal
      government characteristics on oral health practice. One municipality was
      classified as having an intermediate standard of oral health system
      implementation (50%), while the other showed only 11% implementation. The study
      showed that the decentralization process has not been accompanied by an effort to
      improve management capacity in the local oral health services, despite the
      transfer of funds to this area.

PMID- 17552087
TI  - The rapidly changing landscape of biomedical conflicts of interest.

PMID- 17552088
TI  - Bird migration routes and risk for pathogen dispersion into western Mediterranean
      wetlands.
AB  - Wild birds share with humans the capacity for moving fast over large distances.
      During migratory movements, birds carry pathogens that can be transmitted between
      species at breeding, wintering, and stopover places where numerous birds of
      various species are concentrated. We consider the area of the Camargue (southern
      France) as an example to highlight how ad hoc information already available on
      birds' movements, abundance, and diversity can help assess the introduction and
      transmission risk for birdborne diseases in the western Mediterranean wetlands.
      Avian influenza and West Nile viruses are used as examples because birds are
      central to the epidemiology of these viruses.

PMID- 17552089
TI  - Human and animal vaccination delivery to remote nomadic families, Chad.
AB  - Vaccination services for people and livestock often fail to achieve sufficient
      coverages in Africa's remote rural settings because of financial, logistic, and
      service delivery constraints. In Chad from 2000 through 2005, we demonstrated the
      feasibility of combining vaccination programs for nomadic pastoralists and their
      livestock. Sharing of transport logistics and equipment between physicians and
      veterinarians reduced total costs. Joint delivery of human and animal health
      services is adapted to and highly valued by hard-to-reach pastoralists. In
      intervention zones, for the first time approximately 10% of nomadic children (> 1
      11 months of age) were fully immunized annually and more children and women were
      vaccinated per day during joint vaccination rounds than during vaccination of
      persons only and not their livestock (130 vs. 100, p < 0.001). By optimizing use
      of limited logistical and human resources, public health and veterinary services
      both become more effective, especially at the district level.

PMID- 17552090
TI  - Worldwide emergence of extensively drug-resistant tuberculosis.
AB  - Mycobacterium tuberculosis strains that are resistant to an increasing number of
      second-line drugs used to treat multidrug-resistant tuberculosis (MDR TB) are
      becoming a threat to public health worldwide. We surveyed the Network of
      Supranational Reference Laboratories for M. tuberculosis isolates that were
      resistant to second-line anti-TB drugs during 2000-2004. We defined extensively
      drug-resistant TB (XDR TB) as MDR TB with further resistance to > or = 3 of the 6
      classes of second-line drugs. Of 23 eligible laboratories, 14 (61%) contributed
      data on 17,690 isolates, which reflected drug susceptibility results from 48
      countries. Of 3,520 (19.9%) MDR TB isolates, 347 (9.9%) met criteria for XDR TB.
      Further investigation of population-based trends and expanded efforts to prevent
      drug resistance and effectively treat patients with MDR TB are crucial for
      protection of public health and control of TB.

PMID- 17552091
TI  - Tandem repeat analysis for surveillance of human Salmonella Typhimurium
      infections.
AB  - In Denmark, as part of the national laboratory-based surveillance system of human
      enteric infections, all Salmonella enterica serotype Typhimurium isolates are
      currently subtyped by using phage typing, antimicrobial resistance profiles, and
      pulsed-field gel electrophoresis (PFGE). We evaluated the value of real-time
      typing that uses multiple-locus variable-number tandem-repeats analysis (MLVA) of
      S. Typhimurium to detect possible outbreaks. Because only a few subtypes
      identified by PFGE and phage typing account for most infections, we included MLVA
      typing in the routine surveillance in a 2-year period beginning December 2003.
      The 1,019 typed isolates were separated into 148 PFGE types and 373 MLVA types.
      Several possible outbreaks were detected and confirmed. MLVA was particularly
      valuable for discriminating within the most common phage types. MLVA was superior
      to PFGE for both surveillance and outbreak investigations of S. Typhimurium.

PMID- 17552092
TI  - In vitro cell culture infectivity assay for human noroviruses.
AB  - Human noroviruses cause severe, self-limiting gastroenteritis that typically
      lasts 24-48 hours. Because of the lack of suitable tissue culture or animal
      models, the true nature of norovirus pathogenesis remains unknown. We show, for
      the first time, that noroviruses can infect and replicate in a physiologically
      relevant 3-dimensional (3-D), organoid model of human small intestinal
      epithelium. This level of cellular differentiation was achieved by growing the
      cells on porous collagen-I coated microcarrier beads under conditions of
      physiological fluid shear in rotating wall vessel bioreactors. Microscopy, PCR,
      and fluorescent in situ hybridization provided evidence of norovirus infection.
      Cytopathic effect and norovirus RNA were detected at each of the 5 cell passages
      for genogroup I and II viruses. Our results demonstrate that the highly
      differentiated 3-D cell culture model can support the natural growth of human
      noroviruses, whereas previous attempts that used differentiated monolayer
      cultures failed.

PMID- 17552093
TI  - Surveillance of influenza A virus in migratory waterfowl in northern Europe.
AB  - We conducted large-scale, systematic sampling of influenza type A virus in
      migratory waterfowl (mostly mallards [Anas platyrhynchos]) at Ottenby Bird
      Observatory, southeast Sweden. As with previous studies, we found a higher
      prevalence in fall than spring, and among juveniles compared with adults.
      However, in contrast to other studies, we found that prevalence in spring was
      sometimes high (mean 4.0%, highest 9.5%). This finding raises the possibility
      that ducks are capable of perpetuating influenza A virus of different subtypes
      and subtype combinations throughout the year and from 1 year to the next.
      Isolation of the H5 and H7 subtypes was common, which suggests risk for
      transmission to sensitive domestic animals such as poultry. We argue that wild
      bird screening can function as a sentinel system, and we give an example of how
      it could have been used to forecast a remote and deadly outbreak of influenza A
      in poultry.

PMID- 17552094
TI  - Risk for infection with highly pathogenic influenza A virus (H5N1) in chickens,
      Hong Kong, 2002.
AB  - We used epidemiologic evaluation, molecular epidemiology, and a case-control
      study to identify possible risk factors for the spread of highly pathogenic avian
      influenza A virus (subtype H5N1) in chicken farms during the first quarter of
      2002 in Hong Kong. Farm profiles, including stock sources, farm management, and
      biosecurity measures, were collected from 16 case and 46 control chicken farms by
      using a pretested questionnaire and personal interviews. The risk for influenza A
      (H5N1) infection was assessed by using adjusted odds ratios based on multivariate
      logistic regression analysis. Retail marketing of live poultry was implicated as
      the main source of exposure to infection on chicken farms in Hong Kong during
      this period. Infection control measures should be reviewed and upgraded as
      necessary to reduce the spread of influenza A (H5N1) related to live poultry
      markets, which are commonplace across Asia.

PMID- 17552095
TI  - Behavioral risks for West Nile virus disease, northern Colorado, 2003.
AB  - In 2003, residents in 2 adjacent cities in northern Colorado (Loveland and Fort
      Collins) had severe outbreaks of human West Nile virus (WNV) disease.
      Unexpectedly, age-adjusted neuroinvasive disease rates were higher in Loveland
      (38.6 vs. 15.9 per 100,000), which had a more extensive mosquito control program
      and fewer mosquitoes. A survey was conducted to assess differences in personal
      protection and risk practices by each city's residents. During May and June 2004,
      a random-digit dial telephone survey was conducted among adults to assess
      personal protection behavioral practices used to prevent WNV infection during the
      2003 outbreak. After we adjusted for identified risk factors, Loveland residents
      were 39% more likely to report seldom or never using N,N-diethyl-m-toluamide
      (DEET), and approximately 30% were more likely to report being outdoors during
      prime mosquito-biting hours than Fort Collins residents. Personal protective
      practices may directly influence rates of WNV infection and remain important even
      when comprehensive community mosquito control measures are implemented.

PMID- 17552097
TI  - Diversity and distribution of Borrelia hermsii.
AB  - Borrelia hermsii is the most common cause of tickborne relapsing fever in North
      America. DNA sequences of the 16S-23S rDNA noncoding intergenic spacer (IGS)
      region were determined for 37 isolates of this spirochete. These sequences
      distinguished the 2 genomic groups of B. hermsii identified previously with other
      loci. Multiple IGS genotypes were identified among isolates from an island, which
      suggested that birds might play a role in dispersing these spirochetes in nature.
      In support of this theory, all stages of the tick vector Ornithodoros hermsi fed
      successfully on birds in the laboratory and advanced in their life cycle. B.
      hermsii produced a detectable spirochetemia in 1 chicken inoculated
      subcutaneously. Additional work is warranted to explore the role of birds as
      enzootic hosts for this relapsing fever spirochete.

PMID- 17552096
TI  - Matrix protein 2 vaccination and protection against influenza viruses, including
      subtype H5N1.
AB  - Changes in influenza viruses require regular reformulation of strain-specific
      influenza vaccines. Vaccines based on conserved antigens provide broader
      protection. Influenza matrix protein 2 (M2) is highly conserved across influenza
      A subtypes. To evaluate its efficacy as a vaccine candidate, we vaccinated mice
      with M2 peptide of a widely shared consensus sequence. This vaccination induced
      antibodies that cross-reacted with divergent M2 peptide from an H5N1 subtype. A
      DNA vaccine expressing full-length consensus-sequence M2 (M2-DNA) induced M2
      specific antibody responses and protected against challenge with lethal
      influenza. Mice primed with M2-DNA and then boosted with recombinant adenovirus
      expressing M2 (M2-Ad) had enhanced antibody responses that crossreacted with
      human and avian M2 sequences and produced T-cell responses. This M2 prime-boost
      vaccination conferred broad protection against challenge with lethal influenza A,
      including an H5N1 strain. Vaccination with M2, with key sequences represented,
      may provide broad protection against influenza A.

PMID- 17552098
TI  - Population-based laboratory surveillance for AmpC beta-lactamase-producing
      Escherichia coli, Calgary.
AB  - In the Calgary Health Region during 2000-2003, prospective, active, population
      based laboratory surveillance for all cefoxitin-resistant Escherichia coli
      isolates was performed. Isolates were screened with an inhibitor-based disk test,
      and plasmid-mediated types were identified by multiplex PCR with sequencing. A
      total of 369 AmpC beta-lactamase-producing E. coli isolates were identified;
      annual incidence rates were 1.7, 4.3, 11.2, and 15 per 100,000 residents for each
      year, respectively. AmpC beta-lactamase-producing E. coli was 5x more likely to
      be isolated from female than male patients across all age groups except < 1 year.
      Of these isolates, 83% were community onset, and urine was the principal site of
      isolation (90% of patients). PCR showed that 125 (34%) were positive for bla(cmy)
      genes; sequencing identified these enzymes to be CMY-2. In this large Canadian
      region, AmpC beta-lactamase-producing E. coli is an emerging community pathogen
      that commonly causes urinary tract infections in older women.

PMID- 17552099
TI  - Effectiveness of neuraminidase inhibitors for preventing staff absenteeism during
      pandemic influenza.
AB  - We used a deterministic SEIR (susceptible-exposed-infectious-removed) meta
      population model, together with scenario, sensitivity, and simulation analyses,
      to determine stockpiling strategies for neuraminidase inhibitors that would
      minimize absenteeism among healthcare workers. A pandemic with a basic
      reproductive number (R0) of 2.5 resulted in peak absenteeism of 10%. Treatment
      decreased peak absenteeism to 8%, while 8 weeks' prophylaxis reduced it to 2%.
      For pandemics with higher R0, peak absenteeism exceeded 20% occasionally and 6
      weeks' prophylaxis reduced peak absenteeism by 75%. Insufficient duration of
      prophylaxis increased peak absenteeism compared with treatment only. Earlier
      pandemic detection and initiation of prophylaxis may render shorter prophylaxis
      durations ineffective. Eight weeks' prophylaxis substantially reduced peak
      absenteeism under a broad range of assumptions for severe pandemics (peak
      absenteeism > 10%). Small investments in treatment and prophylaxis, if adequate
      and timely, can reduce absenteeism among essential staff.

PMID- 17552100
TI  - Environmental Burkholderia cepacia complex isolates in human infections.
AB  - Members of the Burkholderia cepacia complex (Bcc), found in many environments,
      are associated with clinical infections. Examining diverse species and strains
      from different environments with multilocus sequence typing, we identified > 20%
      of 381 clinical isolates as indistinguishable from those in the environment. This
      finding links the natural environment with the emergence of many Bcc infections.

PMID- 17552101
TI  - Cryptosporidium hominis infection of the human respiratory tract.
AB  - Cryptosporidium oocysts, observed in a natural sputum sample of a patient with
      HIV, were further studied by using DNA markers to determine the species of the
      parasite. C. hominis was identified as the species infecting the patient's
      respiratory tract, a finding that strengthens evidence regarding this pathogen's
      role in human disease.

PMID- 17552102
TI  - Cocirculation of 2 genotypes of Toscana virus, southeastern France.
AB  - Toscana virus (TOSV), an arthropodborne phlebovirus transmitted by sandflies, can
      cause febrile illness and meningitis. The vector of TOSV in France was unknown.
      We detected TOSV RNA in 2 (female Phlebotomus perniciosus) of 61 pools of
      sandflies captured in southeastern France. Two genotypes of TOSV were identified.

PMID- 17552103
TI  - Rapidly fatal Acanthamoeba encephalitis and treatment of cryoglobulinemia.
AB  - We describe a 66-year-old woman with therapy-refractory cryoglobulinemia treated
      with rituximab, plasmapheresis, and steroids; a case of fatal meningoencephalitis
      caused by Acanthamoeba spp. then developed. Such infections are rare and show an
      unusually rapid course (possibly related to rituximab).

PMID- 17552104
TI  - Mouse-to-human transmission of variant lymphocytic choriomeningitis virus.
AB  - A case of lymphocytic choriomeningitis virus (LCMV) infection led to
      investigation of the reservoir. LCMV was detected in mice trapped at the
      patient's home, and 12 isolates were recovered. Genetic analysis showed that
      human and mouse LCMVs were identical and that this LCMV strain was highly
      divergent from previously characterized LCMV.

PMID- 17552105
TI  - Leishmania donovani and cutaneous leishmaniasis, Sri Lanka.
AB  - To investigate the relationship of cutaneous leishmaniasis isolates from Sri
      Lanka to known species, we performed DNA sequencing and microsatellite analyses.
      We identified Leishmania donovani as the agent of Sri Lanka cutaneous
      leishmaniasis and showed that these parasites are closely related to those
      causing visceral leishmaniasis in the Indian subcontinent.

PMID- 17552106
TI  - Depression after infection with West Nile virus.
AB  - Previous reports have noted depression after West Nile virus (WNV) infection. We
      further measured this outcome and found that 31% of patients reported new-onset
      depression and 75% of these had Center for Epidemiologic Studies Depression
      scores indicative of mild-to-severe depression. Physicians should be aware of
      neuropsychiatric consequences of WNV in patients.

PMID- 17552107
TI  - Detection of G12 human rotaviruses in Nepal.
AB  - Of 731 stool specimens collected from children with diarrhea in Kathmandu, Nepal,
      from August 2004 through July 2005, 170 (23.3%) tested positive for rotavirus.
      Reverse transcription-PCR, including a revised G12-specific primer set,
      identified 56 (32.9%) as G2P[4] and 39 (23.0%) as G12 with P[6], P[8], or P[4].

PMID- 17552108
TI  - Clostridium difficile in retail ground meat, Canada.
AB  - Clostridium difficile was isolated from 12 (20%) of 60 retail ground meat samples
      purchased over a 10-month period in 2005 in Canada. Eleven isolates were
      toxigenic, and 8 (67%) were classified as toxinotype III. The human health
      implications of this finding are unclear, but with the virulence of toxinotype
      III strains further studies are required.

PMID- 17552109
TI  - Methicillin-susceptible, doxycycline-resistant Staphylococcus aureus, Cote
      d'Ivoire.
AB  - We report 2 outbreaks of Panton-Valentine leukocidin-positive, doxycycline
      resistant, methicillin-susceptible Staphylococcus aureus infections in French
      soldiers operating in Cote d'Ivoire. In a transssectional survey, nasal carriage
      of this strain was found in 2.9% of 273 soldiers about to be sent to Cote
      d'Ivoire and was associated with prior malaria prophylaxis with doxycycline.

PMID- 17552110
TI  - Intermediate vancomycin susceptibility in a community-associated MRSA clone.
AB  - We describe a case of treatment failure caused by a strain of USA300 community
      associated methicillin-resistant Staphylococcus aureus (MRSA) with intermediate
      susceptibility to vancomycin and reduced susceptibility to daptomycin. The strain
      was isolated from the bone of a 56-year-old man with lumbar osteomyelitis after a
      6-week treatment course of vancomycin for catheter-associated septic
      thrombophlebitis.

PMID- 17552111
TI  - Staphylococcal cassette chromosome mec in MRSA, Taiwan.
AB  - To determine the predominant staphylococcal cassette chromosome (SCC) mec element
      in methicillin-resistant Staphylococcus aureus, we typed 190 isolates from a
      hospital in Taiwan. We found a shift from type IV to type III SCCmec element
      during 1992-2003, perhaps caused by selective pressure from indiscriminate use of
      antimicrobial drugs.

PMID- 17552112
TI  - Clostridium difficile-associated disease in New Jersey hospitals, 2000-2004.
AB  - Recent emergence of a virulent strain of Clostridium difficile demonstrates the
      importance of tracking C. difficile incidence locally. Our survey of New Jersey
      hospitals documented increases in the rates of C. difficile disease (by 2-fold),
      C. difficile-associated complications (by 7-fold), and C. difficile outbreaks (by
      12-fold) during 2000-2004.

PMID- 17552113
TI  - Drug-resistant nontyphoidal Salmonella bacteremia, Thailand.

PMID- 17552114
TI  - Fulminant supraglottitis from Neisseria meningitidis.

PMID- 17552115
TI  - gyrA mutations in fluoroquinolone-resistant Clostridium difficile PCR-027.

PMID- 17552116
TI  - New strain of influenza A virus (H5N1), Thailand.

PMID- 17552117
TI  - Kala-azar control, Uganda.

PMID- 17552118
TI  - Chikungunya virus infection in traveler to Australia.

PMID- 17552119
TI  - Avian influenza A (H5N1) age distribution in humans.

PMID- 17552120
TI  - Toxoplasma gondii, Brazil.

PMID- 17552121
TI  - CTX-M extended-spectrum beta-lactamases, Washington State.

PMID- 17552122
TI  - HIV and hepatitis C virus coinfection, Cameroon.

PMID- 17552123
TI  - Amebic liver abscess in HIV-infected patients, Republic of Korea.

PMID- 17552124
TI  - Pregnancy and emerging diseases.

PMID- 17552125
TI  - Escherichia coil cluster evaluation.

PMID- 17552126
TI  - Assessing the potential of national strategies for electronic health records for
      population health monitoring and research.
AB  - OBJECTIVES: This report assesses the potential of national strategies for
      electronic health records for population health monitoring and research. METHODS:
      This study: (1) Reviewed national strategies for electronic health records in
      Australia, Canada, England, and New Zealand, through written materials available
      before January 2006. (2) Identified the potential of national strategies for
      electronic health records for population health monitoring and research through
      interviews with 96 experts in the U.S., Australia, Canada, England, and New
      Zealand. (3) Delineated fundamental issues that must be confronted to maximize
      the contribution of national strategies for electronic health records to
      population health monitoring and research. RESULTS: National strategies for
      electronic health records reflect the political, healthcare, and market systems
      of individual countries. National strategies also reflect technical decisions and
      political judgments. National strategies are evolving, and passing through stages
      of conceptualization, design, pilot testing, and implementation. Only England has
      moved to implementation. Population health monitoring and research are secondary
      to the primary uses of clinical care and management in all national strategies
      for electronic health records. Only England has conceptualized, designed, and is
      implementing the use of electronic health records for population health
      monitoring and research. Canada's strategy includes communicable disease
      surveillance, but not broader population health monitoring for developing health
      statistics. This study identifies definitional, numerator, denominator, and
      overarching issues that must be evaluated in assessing the potential of national
      strategies for electronic health records for population health monitoring and
      research. It delineates success factors that increase the potential for those
      national strategies to contribute to population health monitoring and research.
      Finally, this study assesses barriers that must be overcome if national
      strategies for electronic health records can contribute to population health
      monitoring and research, and especially to health statistics.

PMID- 17552127
TI  - "Just scanning around" with diagnostic medical ultrasound: should states regulate
      the non-diagnostic uses of this technology?
AB  - This article examines how the non-diagnostic uses of medical ultrasound may
      violate the prudent use of this technology and supports the proposal of state
      based legislative efforts to protect consumers from abuse. The author identifies
      the potential health risks to consumers and reviews the existing federal and
      state regulations, ultimately recommending increased legislation and mandated
      control of this technology.

PMID- 17552128
TI  - Excusable neglect in malpractice suits against radiologists: a proposed jury
      instruction to recognize the human condition.
AB  - This article unwraps the nature and source of human errors involved in Radiology,
      revealing unique elements of the specialty that warrant special consideration in
      medical malpractice cases. The authors compare these errors to negligent
      practices in other professions and conclude that a general concept of negligence
      cannot adequately address the complexities of decision-making in Radiology. After
      analyzing legal precedent, they develop an innovative jury instruction that
      recognizes particular situations of error in Radiology that occur in the absence
      of negligence.

PMID- 17552129
TI  - Give them what they want? The permissibility of pediatric placebo-controlled
      trials under the best pharmaceuticals for children act.
AB  - This article discusses the Best Pharmaceuticals for Children Act and the FDA's
      request for placebo-controlled studies of drugs to treat OCD and depression in
      children. First, the article explains the need to test drugs in children and
      examines the reasons this testing has not occurred. Next, the article describes
      the legislative and administrative responses to remedy this lack of research and
      assesses the ethics and legality of their implementation. The article concludes
      that these initiatives are legally and ethically acceptable until a safe and
      effective treatment is determined--at which point the use of placebos in
      pediatric testing must be replaced with active controls.

PMID- 17552130
TI  - Releasing managed care's chokehold on healthcare providers.
AB  - This article addresses the imbalance of power between managed care organizations
      and physicians regarding the content of treatment information given to patients.
      The author provides a thoughtful discussion surrounding informed consent issues
      in a managed care environment, and how managed care organizations maintain their
      control over physicians. The author concludes by offering varied and insightful
      methods to even out the disparity of power.

PMID- 17552131
TI  - Will pay for performance be worth the price to medical providers? A look at pay
      for performance and its legal implications for providers.
AB  - This article explores the legal implications of pay for performance programs from
      the perspective of healthcare providers. The author provides an informative
      background on the emergence of pay for performance programs and examines the
      structure and operation of these programs. She then explores the liability issues
      of health plans and managed care organizations and delves into evidentiary issues
      related to pay for performance information. Her article concludes with some
      practical suggestions for providers in preparing for an expansion of these
      quality initiatives.

PMID- 17552132
TI  - The states "race" with the federal government for stem cell research.
AB  - This article presents an innovative study of the effect of individual states and
      private institutes in pushing forward stem cell research despite a federal ban on
      creating new stem cell lines. The author analyzes the impact of state
      legislation, proposing that states are reacting to federal policy by serving as
      laboratories for what is traditionally federally funded biomedical research.

PMID- 17552133
TI  - Conscience clauses and oral contraceptives: conscientious objection or calculated
      obstruction?
AB  - This article examines the ethical and legal implications of conscience clauses,
      which allow pharmacists to refuse to fill prescriptions for oral contraceptives
      due to their belief that they may constitute abortifacients. The author provides
      an informative background on contraception and the history of how abortion has
      been viewed in this country, then takes a critical look at some of the conscience
      laws already in existence, using a bioethical framework to examine them. She
      concludes by providing suggestions to reduce the negative ethical implications
      resulting from the enactment of conscience clauses.

PMID- 17552134
TI  - Is obesity really the next tobacco? Lessons learned from tobacco for obesity
      litigation.
AB  - This article draws important lessons from the history of tobacco litigation that
      can be applied to the current obesity problem in the United States. The author's
      close analysis of potential issues surrounding the obesity problem in this
      country yields the conclusion that litigation alone may not be the best answer.
      Her article offers a compelling perspective on the history of tobacco litigation,
      a thorough analysis of the issues surrounding the obesity problem and several
      potential perspectives on dealing with the situation at hand.

PMID- 17552135
TI  - Drug deals in 2006: cutting edge legal and regulatory issues in the
      pharmaceutical industry.
AB  - Set amidst the backdrop of rising prescription drug costs and a renewed
      governmental commitment to combating fraud, this article highlights recent
      enforcement actions against the pharmaceutical industry. In an effort to clarify
      today's turbulent regulatory landscape, the authors also explore the elements of
      a successful compliance program for pharmaceutical manufacturers and identify the
      major areas of concern for the future.

PMID- 17552136
TI  - The fundamental law that shapes the United States health care system: is
      universal health care realistic within the established paradigm?
AB  - In this article, the author draws from his own experience as a doctor in
      describing the issues the uninsured patient population faces. Pointing out that
      neither the U.S. Constitution nor case law provides a positive right to health
      care, the author describes the parameters of federal health care funding and
      ultimately concludes that universal health care cannot be fully achieved in the
      U.S.

PMID- 17552137
TI  - Earthworm paste (Lampito mauritii, Kinberg) alters inflammatory, oxidative,
      haematological and serum biochemical indices of inflamed rat.
AB  - Experiments were conducted to understand the therapeutic properties such as anti
      inflammatory, anti-oxidative, haematological and serum biochemical markers of
      earthworm paste (EP) derived from an indigenous species Lampito mauritii
      (Kinberg), in comparison with the standard anti-inflammatory drug- aspirin, on
      Wistar albino rat (Rattus norvegicus). Administration of earthworm paste of
      Lampito mauritii at the rate of 80 mg/kg into albino rats which were induced of
      inflammation, was found to reduce inflammation, restore the levels of
      antioxidants-reduced glutathione, glutathione peroxidase, superoxide dismutase,
      catalase and thiobarbituric acid reactive substances, normalise the values of
      erythrocyte, leukocyte, differential levels of neutrophils, lymphocytes,
      eosinophils, haemoglobin and serum biochemical contents e.g., protein, albumin,
      glucose, cholesterol, acid and alkaline phosphatase, electrolytes e.g., sodium,
      potassium and chloride. The anti-inflammatory activity together with antioxidant
      property of EP seems to be due to the high polyphenolic content of earthworm
      tissue.

PMID- 17552138
TI  - Vertebroplasty in the treatment of vertebral metastases: clinical cases and
      review of the literature.
AB  - Bone metastases are the most common tumours affecting the musculoskeletal system.
      The most frequently affected area of the skeleton is the spine. The vertebral
      bodies are reached largely via the bloodstream and neoplastic substitution of the
      bone tissue causes progressive structural destruction leading to loss of
      stability and compression of the intracanal nerve structures. The treatment of
      bone metastases in the spine is different and controversial, mostly because of
      the wide spectrum of clinical and radiographic pattern of the local and systemic
      disease. Percutaneous vertebroplasty is emerging as one of the most promising new
      interventional procedures for relieving (or reducing) pain and improve stability.
      In this article we review indications, contraindications, technique, and
      complications of percutaneous vertebroplasty in spine metastases.

PMID- 17552139
TI  - Solitary fibrous tumor of the urinary bladder: report of a case with long-term
      follow-up and review of the literature.
AB  - Solitary fibrous tumor (SFT) is a neoplasm typically arising in the pleura. Yet,
      extrapleural cases have been described and are a common cause of diagnostic
      pitfalls, especially when met in unusual sites. We report the clinical and
      pathological features of a case of SFT arising in a rather unusual site, the
      urinary bladder, the seventh reported to date in the English literature and the
      first with long term follow-up. Differential diagnosis from other spindle cell
      neoplasms of the bladder can be problematic. Prognosis of this neoplasm is
      obscure and long-term follow-up is required for all cases of solitary fibrous
      tumor. Solitary fibrous tumor is a rare mesenchymal tumor of the urinary bladder,
      but should always be considered in the differential diagnosis of spindle cell
      neoplasms encountered in the lower genital tract.

PMID- 17552140
TI  - Morphological and functional changes of cardiovascular system in postmenopausal
      women.
AB  - BACKGROUND: The incidence of cardiovascular events in reproductive age women is 3
      times lower than in men, whereas this ratio noticeably changes on menopausal
      beginning. Postmenopausal women are more exposed to the effects of risk factors,
      which are present in a noticeably different entity in physiological or surgical
      menopause; and in the latter whether on substitutive hormonal treatment or not.
      METHODS: This study, carried out in Rome and Latina, has involved 743
      postmenopausal women, of whom 545 with physiological menopause and 198 with
      iatrogenic menopause. RESULTS: The average blood pressure value as well as the
      incidence of hypertension, hypercholesterolemia, diabetes mellitus, obesity and
      smoking have a significantly different trend in physiological versus iatrogenic
      postmenopausal women; and in the latter whether on substitutive hormonal
      treatment or not. CONCLUSIONS: Studying life-style and evaluating risk factors in
      postmenopausal women, and giving an up-to-date view about the prevalence oh
      health conditions at risk, will allow us to promote both primary and secondary
      prevention actions.

PMID- 17552141
TI  - Toxic epidermal necrolysis and Steven Johnson syndrome: 11-years experience and
      outcome.
AB  - BACKGROUND AND OBJECTIVE: Toxic epidermal necrolysis and Steven Johnson syndrome
      are rare diseases that usually follow drug-exposures. The authors present one
      retrospective study with their management and focus their retrospective analysis
      on finding prognostic factors. MATERIALS AND METHODS: We reviewed charts of
      admitted patients from January 1995 to December 2005. Only those with an
      histologic-proved diagnosis were included in the study. Causative drugs,
      symptoms, management and outcome were recorded and analysed. RESULTS: We found 32
      patients that met inclusion criteria. Mortality rate was 34.4% (11/32). Age,
      delay of referral, Total Burn Surface Area, white blood cells, creatinine, blood
      sodium, immunoglobulins therapy and more than two different types of blood
      bacterial species isolated were significantly correlated with death (p < 0.05).
      CONCLUSIONS: These data confirm prognostic factors already present in literature
      and find that the number of different bacterial species isolated from blood
      increase mortality. Further prospective studies are necessary to confirm these
      findings.

PMID- 17552142
TI  - Advanced grades of bleeding hemorrhoids in a young boy.
AB  - We report a case of advanced grades of bleeding hemorrhoids in a 10-yrs-old boy,
      who had a history of bleeding per rectum since he was 5 year of age. The
      diagnosis was made on anoscopic examination after ruling out other colorectal
      pathologies by a full-length colonoscopy. There was no evidence of portal
      hypertension. He was successfully treated with radiofrequency ablation and
      plication of hemorrhoids using a Ellman radiofrequency generator. Though rare to
      be found at the age of ten years without any obvious etiology, hemorrhoids should
      be considered as one of the causes of bleeding per rectum in children.

PMID- 17552143
TI  - Ropivacaine induced acute neurotoxicity after epidural injection.
AB  - Ropivacaine is an amide-type long acting local anaesthetic. According to
      experimental and human data, its toxicity for Central Nervous System (CNS) and
      Cardiovascular System (CVS) is considered lower than toxicity related to
      bupivacaine, the now-a-days accepted golden standard for long acting local
      anaesthetics. Nevertheless, reports about this kind of accidents are fairly
      numerous. Aim of this short paper is to describe, primarily from a subjective
      point of view, CNS symptoms a patient (one of the Authors) suffered by an acute
      toxic reaction during an epidural block, and to stress the need to pay attention
      to safety measures in the practice of loco-regional anaesthesia and epidural
      blockade.

PMID- 17552145
TI  - [A review on research of raw material and cut crude drug of Herba epimedii in
      last ten years].
AB  - Researches on taxonomy, resources, cultivation, quality, chemicals and processing
      of Herba Epimedii in last ten years were reviewed. The taxonomy of Chinese
      species in "Flora of China (Vo1.29)" (published in 2001) and "The genus Epimedium
      and other herbaceous Berberidaceae" (published in 2002) were mainly introduced
      and commented. The quality evaluation of raw material of Herba Epimedii, and
      effects of distribution, growing time and medicinal part on the quality were
      summarized.

PMID- 17552144
TI  - [Nephritic model induced by anti-Thy1.1 monoclonal antibody and its application
      to study on Chinese materia medica].
AB  - The anti-Thy1.1 glomerulonephritis (GN) model induced by anti-Thy1.1 monoclonal
      antibody (mAb) is a widely used animal model for human mesangial proliferative
      glomerulonephritis (MsPGN), which is characterized by significant proteinuria and
      acute or progressive mesangial injury following the complement-mediated
      mesangiolysis and glomerular inflammatory cell infiltration. In this review, it
      has been discussed that the pathogenesis of reversible anti-Thy1.1 GN or
      irreversible anti-Thy1.1 GN induced by mAb 1-22-3 injection, the mechanisms
      governing inflammatory cells infiltration and several injurious cytokines in
      glomeruli, and some of the processes involved in the resolution of mesangial
      lesion such as mesangial cell proliferation and matrix expansion. Using these
      models, it has been reported to examine the effects of Chinese materia medica,
      including multi-glycoside of Tripterygium wilfordii Hook. f. (GTW) and Sairei-to
      on mesangial damage and proteinuria, and then to clarify the mechanism of these
      herbs at molecular level by examining the effects on various injurious factors.

PMID- 17552146
TI  - [Advances of sustained/controlled release pellets in traditional Chinese
      medicine].
AB  - Pellets are multiple-unit drug delivery system, which have good fluidity, release
      stability and uniformity. With preparation techniques and excipient materials
      gradually established, pellets play an important part in the development of
      sustained/controlled release drug delivery system. The recent advances in pellets
      including the release mechanism, preparation methods, excipients and the
      characteristics in vivo for the sustained/controlled release pellets in
      traditional Chinese medicine (TCM) were reviewed in order to provide the
      strategies and rational methods for further investigations and applications.

PMID- 17552147
TI  - [Determination of calceolarioside B in Caulis Akebiae by RP-HPLC].
AB  - OBJECTIVE: To establish a quantitative method for calceolarioside B in Caulis
      Akebiae. METHOD: The samples were separated at 35 degrees C on a Phenomenex Luna
      C18 column eluted with methanol-water-phosphoric acid (35: 65: 0.05) as mobile
      phase. Flow rate was at 1.0 mL x min(-1) and the detection wavelength was at 330
      nm. RESULT: The calibration curve was linear over the range from 0. 04 to 0. 86 g
      (r = 0. 9998) and the average recovery was 97.2%. 39 Crude drug materials
      collected from different areas were determined and the contents of
      calceolarioside B in Caulis Akebiae were fluctuated from 0. 021% to 0. 745%.
      CONCLUSION: The method is simple and repeatable and could be used for the quality
      control of Caulis Akebiae.

PMID- 17552148
TI  - [Study on seed quality test and quality standard of Changium smyrnioides].
AB  - OBJECTIVE: To study seed quality test methods, and provide basis for establishing
      seed quality standard of Changium smyrnioides. METHOD: According to the seed
      testing regulations, the seed quality of C. smyrnioides from different producing
      area and in different growing years was measured. RESULT AND CONCLUSION: The
      range of seed purity, weight per 1000 seeds, seed moisture content, seed
      viability were determined and the primary seed quality classification standard
      was established.

PMID- 17552149
TI  - [In vitro studies on asexual embryos and regenerated plantlets obtained from leaf
      organ of Panax notoginseng].
AB  - OBJECTIVE: To study and improve the tissue culture technology of Panax
      notoginseng. METHOD: Using the callus of leaf blade and leafstalk of P.
      notogingseng as explants, MS + 2, 4-D 1.5 mg x L(-1) as basal medium, the
      formation of asexual embryos was induced by added LFS, BA, KT or ZT 0.5 mg x L(
      1), and cultured in dark. It cultured then in 2000 lx of illumination for 10-12 h
      x d(-1) to induce the asexual embryos germinating and developing to be the
      regenerated-plantlet. RESULT AND CONCLUSION: Only the medium added with LFS could
      induce the formation of asexual embryos, and made it developed to be regenerated
      plantlet. The inducing ratio of asexual embryos reached about 85%, and 30% of
      asexual embryos could grow and develop as robust regenerated-plantlets.

PMID- 17552150
TI  - [Study on alpha-asarone reservoir-type patch].
AB  - OBJECTIVE: To prepare the alpha-asarone reservoir patch and investigate its
      release and transdermal absorption characteristics in vitro. The efficient
      enhancers were chosen to improve the drug's permeation rate. METHOD: The alpha
      asarone reservoir patch was prepared using 1% hydroxypropyl methylcellulose
      (HPMC) of ethanol solution as medium and ethylene vinyl acetate (EVA) membrane to
      control the release of drug. The Franz diffusion cells were used and several
      permeation enhancers were evaluated. High performance liquid chromatorgraphy
      (HPLC) was used to determine alpha-asarone's content and permeation rate. RESULT:
      The release mechanisms of alpha K-asarone patch in vitro coincided with zero
      order kinetic. 30% ethanol cooperates with 1% Isopropyl Myristate (IPM) have the
      best effect on permeation of the patch. The permeation rate reaches (20.67 +/-
      1.33) microg x cm(-2) h(-1). CONCLUSION: Ethanol combined with IPM is good
      permeation enhancer, which facilitated the permeation of alpha K-asarone to fit
      the clinical requirements. However, the further studies of the skin's stimulation
      and bioavailability are needed.

PMID- 17552151
TI  - [Effects of 2-n-nonyl-1,3-dioxolane as an enhanceron transdermal absorption of
      Salvia miltiorrhiza gel].
AB  - OBJECTIVE: To choose the most suitable concentration of 2-n-nonyl-1,3-dioxolane
      as a penetration enhancer in tanshinone gel preparation. METHOD: In vitro,
      transdermal absorption was studied using improved Frans equipment and rats skin.
      Tanshinone II A was tested by HPLC. RESULT: The 4.0% concentration of 2-n-nonyl
      1,3-dioxolane enhanced the transdermal absorption significantly in the
      preparation. CONCLUSION: 2-n-nonyl-1,3-dioxolane was a new effective permeaton
      enhancer.

PMID- 17552152
TI  - [Fundamentally study on mathematical kinetic model of component extraction from
      FTCM].
AB  - OBJECTIVE: To establish the mathematical kinetic model of the components
      extracted from the FTMC (formulae of the traditional Chinese medicine) and
      analyze parameters of the astragaloside IV extracted from the BYHWD (Buyang
      Huanwu decoction). METHOD: The model, including algebra and differential groups,
      have been set up according to the FICK discipline and Noyes-whitney soluted
      theories, as well as two transfer diffusive processes ((1) from protoplasate to
      apoplasmic, also from material compartment interior cell membrane to outside
      compartment; (2) apoplasmic to solution, also from outside compartment to solvent
      compartment) on components extraction from the FTMC. The equation groups,
      according to laplace transform, have been given a expression as solutions, which
      indicate the quantitative changes of the component concentration in solvent vs.
      time. The model kinetic parameters have been analyzed, meanwhile the parameters
      of the astragaloside IV in the BYHWD under 100 degrees C, extracted by water,
      have been analyzed by way of this model: RESULT: It has been established a
      mathematical model that consists of three parts of e exponent. The kinetic
      parameters: M, alpha, N, beta, L, pi, K, k1', k2', rho1, rho2, tmax, Cmax, AUC,
      w0, P, D of the BYHWD were respectivelly 0.061 27% , 0.280 2 min(-1), - 1.027% ,
      0.008 965 min(-1), 1.077%, 0.002 665 min(-1), 3.451 x 10(-3) min(-1), 3.188 x 10(
      3) min(-1), 0.375 9 min(-1), 1.420 min, 0.754 7 min, 184.9 min, 0. 0572 1 mg x
      mL(-1), 289.9 min, 0.070 11%, 46.24%, 22. 35%. CONCLUSION: The kinetic model,
      applied to isolated system, can have been of the rule of multiplex linear. Each
      parameters can be analyzed completely.

PMID- 17552153
TI  - [Studies on chemical constituents in fruits of Eucalyptus globulus].
AB  - OBJECTIVE: To study the chemical constituents in the fruits of Eucalyptus
      globulus Labill. METHOD: The chemical constituents were isolated by various
      column chromatographic methods and structurally elucidated by IR, NMR and MS
      evidences. RESULT: Fifteen compounds were obtained and identified as beta
      sitosterol (1), betulinic acid (2), stigmasterol (3), euscaphic acid (4), 2a
      Hydroxybetulinic acid (5), macrocarpal B (6), macrocarpal A (7), oleanolic acid
      (8), 3,4,3'-O-trimethylellagic acid (9), 3-O-methylellagic acid 4'-O-(2"-O-acetyl
      )-alpha-L-rhamnopyranoside (10), camaldulenside (cypellocarpin C, 11), 3-O
      methylellagic acid 4'-O-alpha-L-rhamnopyranoside (12), 3-O-methylellagic acid
      (13), ellagic acid (14), and gallic acid (15). CONCLUSION: Compounds 4 and 5 from
      genera Eucalyptus, 1, 3 and 11 from plant E. globulus, and 6, 7, 9 and 15 from
      the fruits of E. globulus were isolated for the first time.

PMID- 17552154
TI  - [Studies on chemical constituents of Cynanchum forrestii].
AB  - OBJECTIVE: To study the chemical constituents of Cynanchum forrestii. METHOD:
      Chromatographic techniques were applied to isolated chemical constituents. The
      structures were identified on the basis of physico-chemical constants and
      spectroscopic data. RESULT: Eight compounds were isolated from the 95% ethanol
      extract of the roots of C. forrestii and elucidated as ( + ) -5'
      methoxyisolariciresinol 3a-O-beta-D-glucopyranoside (1), hexahydroxycholest-7-en
      6-one (2), tylophorinidine (3), sucrose (4), palmitic acid (5), beta-sitosterol
      (6), daucosterol (7), nonanedioic acid (8). CONCLUSION: Compounds 1-3 from this
      genus, and compounds 4-8 from the plant were obtained for the first time.

PMID- 17552155
TI  - [Determination of aisaticoside in Centella asiatica extract by HPLC-ELSD].
AB  - OBJECTIVE: A HPLC-ELSD method was established for the simultaneous quantitative
      determination of asiaticoside in Centella asiatica extract. METHOD: The column
      was packed with 5 m HIQ C18 stationary phase. The mobile phase consisted of
      acetonitrile-water, eluted in gradient mode. The temperature of drift tube was
      105 degrees C and the nebulizer nitrogen flow rate was 2.9 L min(-1). RESULT: The
      linear ranges of the asiaticoside were 0.35-7.0 microg. The recovery of the
      asiaticoside in C. asiatica extract was 94.9% (RSD 1.7%). CONCLUSION: The method
      is reliable, simple, precise and could be used for the quality control of C.
      asiatica extract.

PMID- 17552156
TI  - [Analysis of constituents of essential oils from fresh and dried pericarp of
      citrus sinensis by GC-MS].
AB  - OBJECTIVE: To analyze and compare the constituents of the essential oils from the
      fresh and dried pericarps of Citrus sinensis. METHOD: The essential oils from the
      fresh and dried pericarps of C. sinensis were extracted by water steam
      distillation method and analyzed by GC-MS. RESULT: 28 and 25 components were
      identified from the essential oils of the fresh and dried pericarps of C.
      sinensis respectively, 37 components were identified from both samples totally,
      among which 26 components were identified in the essential oils of the pericarps
      of C. sinensis for the first time. CONCLUSION: The most components in both oil
      samples were similar and main component of the both oils was limonene (90. 16%
      and 77. 34%).

PMID- 17552157
TI  - [Determination of butylidenephthalide in Ligusticum chuanxiong by HPLC].
AB  - OBJECTIVE: To determine butylidenephthalide in Ligusticum Chuanxiong with RP
      HPLC. METHOD: The sample was extracted with methanol using sonication. The ESTD
      was used to quantify butylidenephthalide. HPLC separation was carried out in a
      Hypersil ODS columm (4.6 mm x 150 mm, 5 microm) , eluted at 1 mL x min(-1) with
      methanol-5% isopropyl alcohol (60: 40) at 25 degrees C. The detection wavelength
      was 230 nm. RESULT: The linear range was 0.07-0.7 microg for butylidenephthalide.
      The average recovery was 95.3%, and RSD was 2.3% (n =6). CONCLUSION: This method
      was simple and could be used to determine butylidenephthalide with satisfactory
      accuracy and reproducibility.

PMID- 17552158
TI  - [Effects of Tongxinluo capsule on atherosclerosis obliterans in iliofemoral
      artery of rabbits].
AB  - OBJECTIVE: To explore the effects of Tongxinluo capsule (TXL) on the
      atherosclerosis obliterans (ASO) in iliofemoral artery of rabbits. METHOD:
      Rabbits were randomly divided into 7 groups: sham, model, TXL (0.8, 0.4, 0.2 g x
      kg(-1)), Tongsaimai tablet (0.8 g x kg(-1)) and Laishike (0.002 g x kg(-1)). The
      animal model of ASO was established with a combined method of mechanical trauma,
      immunologic injury and high fat fodder feeding. Rabbits were administrated the
      drugs 8 weeks after surgery. The levels of TC, TG, HDL-C and LDL-C in serum were
      determined at the time points below: pre-experiment (0 week), pre-drug
      administration (8 weeks post-surgery), 4 weeks after drug administration (12
      weeks post-surgery), 8 weeks after drug administration (16 weeks post-surgery),
      12 weeks after drug administration (20 weeks post-surgery). Meanwhile, the
      behavioral study was performed, the distal skin temperature of the injured hind
      limb detected. The histopathological changes in iliofemoral artery were examined
      after opacification. RESULT: The levels of TC, TG, LDL-C, VLDL-C and TC/HDL-C
      were decreased significantly in serum of ASO rabbits. The severity of lameness in
      the injured hind limb was improved. The distal skin temperature was increased.
      The thickness and the ratio of intima area of the iliofemoral artery of the
      injured hind limb were decreased, while the stenosis extent was improved.
      CONCLUSION: TXL might be beneficial to modulate blood lipid, as well as the
      prevention and treatment for ASO.

PMID- 17552159
TI  - [Effect of protein and anthraquinone glucosides from Semen Cassia on learning and
      memory capacity and related substances of senile mice induced by D-galactose].
AB  - OBJECTIVE: To investigate actions of protein and anthraquinone glucosides from
      Semen Cassia on learning and memory capacity and related substances of senile
      mice induced by D-galactose. METHOD: The subacute senile mouse models induced by
      injection of D-galactose subcutaneously were used. RESULT: Protein and
      anthraquinone glucosides from Semen Cassia could improve the learning and memory
      capacity of senile mice. Protein and anthraquinone glucosides from Semen Cassia
      not only inhibited the increase of malondialdehyde (MDA) in cerebrum of senile
      mice, but also enhanced the level of superoxide dismutase (SOD) in cerebrum and
      lessened the lipofuscin (LF) in liver tissue of senile mice. Protein from Semen
      Cassia could reduce the content of monoamine oxidase (MAO) in cerebrum of senile
      mice. CONCLUSION: Protein and anthraquinone glucosides from Semen Cassia could
      improve the learning and memory capacity of senile mice and delay aging.

PMID- 17552160
TI  - [Effect of olive antihyperlipidemia capsule on low and high density lipoprotein
      receptor in rat liver gene expression in hyperlipmia rat liver].
AB  - OBJECTIVE: To study on the regulatory mechanism of lipid metabolism disorders in
      the blood fat of hyperlipemia rat model with Olive Antihyperlipidemia capsule,
      and do systematic observation on the functions of this medicine on low And high
      density lipoprotein receptor in rat liver gene expression, and then to clarify
      the mechanism of action of this medicine on treating hyperlipemia. METHOD: To
      select SD rat as investigated subject. The hyperlipemia rat models were made with
      feeding high-fat forage and were randomly divided into six groups based on the
      total cholesterol level at the ratsfasting for 12 hours: group A, B, C, D, E and
      group F. The samples in the research were collected and analyzed the changes of
      LDLR/SR-B1 gene expression in rat's liver by RT-PCR. RESULT: Olive
      Antihyperlipidemia capsule can markedly enhance LDLR/SR-B1 gene expression in
      rat's liver and finally accomplish the purpose of reducing blood fat. The
      experiment shows this medicine has the remarkable effect on hyperlipidemia and
      proved the theoretical system of treating hyperlipemia for curing the liver is
      correct. CONCLUSION: Olive Antihyperlipidemia capsule has an applicable value on
      preventing the cause, enhance LDLR/SR-B1 gene expression in rat's liver and
      finally accomplish the purpose of reducing blood fat and development of
      hyperlipemia and its complications.

PMID- 17552161
TI  - [Effects of Salvia miltiorrhiza on Chlamydia trachomatis mice of salpingitis].
AB  - OBJECTIVE: To study the effects of Salvia miltiorrhiza on treatment of Chlamydia
      trachomatis salpingitis (CTS) and fibrosis. METHOD: A mouse model for CTS was
      estahlished in C3H/He by intravaginal inoculation. after 3 weeks mice were
      randomly divided into 3 groups. Only Azithromyxin was given orally, Azithromyxin
      and early S. miltiorrhiza given, or Azithromyxin and later S. miltiorrhiza given.
      After 10 weeks, observe the change of oviduct of mice, observe the
      histopathologic change and analysis collagen histochemical index. RESULT: 3
      Treatment groups induce tubal occlusion and hydrosalpinx decreased and the
      collagen histochemical index decreased significantly than those of no treatment
      given (P < 0.05). Early S. miltiorrhiza given group induce tubal occlusion and
      hydrosalpinx decreased and the collagen histochemical index decreased
      significantly than only Azithromyxin group or later S. miltiorrhiza given group
      (P <0.05). CONCLUSION: When we treat CTS genital infection with Azithromyxin, if
      we can give S. miltiorrhiza treatment as early as possible, it may decrease tubal
      occlusion and hydrosalpinx. significantly inhibit fibrosis maybe one of its
      pharmacologic mechanismin.

PMID- 17552162
TI  - [Shengdi injection on rat model of lung inflammation induced by
      lipopolysaccharides].
AB  - OBJECTIVE: To investigate the effect of Shengdi injection on rat model of lung
      inflammation. METHOD: The rat model was established by intratrachea instillation
      of lipopolysaccharides (LPS). The total and different white blood cell counts in
      bronchoalvoelar lavage fluid (BALF) were performed and the level of tumor
      necrosis factor-alpha (TNF-alpha), superoxide anion radical (O2-) and
      myeloperoxidase (MPO) was measured, as well as pathologic change of pulmonary
      tissue was tested. RESULT: Shengdi injection could depress the increasing of the
      amount of total white blood cells and neutrophils and inhibit the increasing of
      TNF-alpha, O2-, MPO caused by LPS, as well as relieve the pathologic change
      including Neutrophils infiltrating and mucous edema in tracheae after intravenous
      administration. While it did not show the effect on monocyte, and histological
      lesion of the lung tissue. CONCLUSION: Shengdi injection shows some anti
      inflammatory effect in rat lung induced by LPS and it can be concluded
      tentatively that anti-inflammatory, inhibiting the release of cytokine and
      inflammatory medium, and antioxidation are some of the mechanism of its effect on
      COPD.

PMID- 17552163
TI  - [Effect of Galla Chinesis on the demineralization of dental root tissue in pH
      cycling model].
AB  - OBJECTIVE: To evaluate the anti-demineralization efficacy of Galla Chinesis in pH
      cycling model for elucidating the anti-root caries mechanism. METHOD: Anti
      demineralization efficacy evaluation of the natural medicine in the pH-cycling
      models was used . Sound human root blocks were pH-cycled through the treatment
      solution, acidic buffer and neutral buffer. The cycling times for
      demineralization study were 12 times, 2 times per day. The acidic buffers were
      retained for calcium analysis by atomic adsorption spectroscopy. The sections of
      blocks were analysed after pH-cycling by CLSM. Treatments were 4 g x L(-1). Galla
      Chinesis, 1 g x L(-1) NaF solution and distilled water. RESULT: Galla Chinesis
      was found to inhibit the demineralization in the pH cycling model. Although the
      effect was not as good as fluoride, there was no significant difference between
      the two groups. CONCLUSION: These data suggest that Galla Chinesis could modulate
      the mineralisation behaviour of root tissue in a defined chemical circumstance.
      These findings support the proposition that Galla Chinesis may be a promising
      anticaries natural medicine in the future.

PMID- 17552164
TI  - [Effective of ginkgolides on expression of apoptosis related gene during PC12
      cells glucose deprivation].
AB  - OBJECTIVE: To investigate the protective effects of ginkgolides on glucose
      deprivation-induced apoptosis in PC12 cells and the mechanism underlying the
      protective effect. METHOD: PC12 cells were treated under glucose deprivation, and
      the proliferation was determined by tetrazolium (MTT) assay. Furthermore, the
      mRNA levels of Bcl-2, Bax, c-myc were measured by Fluorescence Quantitative PCR
      (FQ-PCR). RESULT: Ginkgolides could markedly inhibit the injury of glucose
      deprivation on the PC12 cells and increase the cell proliferation compared with
      the model groups (P <0.01). Ginkgolides could up-regulate Bcl-2 and down-regulate
      Bax and c-myc at 12 h, respectively. There were no significant differences in the
      Bcl-2 and Bax levels in both groups at 24 h, and ginkgolides only reduced the
      elevation of c-myc from 4. 32-fold to 2. 87-fold at this time. CONCLUSION:
      Ginkgolides are able to protect the injured PC12 cells against cell apoptosis.
      During the early period of glucose deprivation, Bcl-2, Bax and c-myc were
      regulated to inhibit cell apoptosis by ginkgolides. After that, ginkgolides seems
      inhibit the apoptosis through attenuating the elevation of c-myc.

PMID- 17552165
TI  - [Approaching molecular imaging].
AB  - In this paper the concept of molecular imaging is introduced, and its importance
      is addressed. Besides, the key points of molecular imaging are briefly reviewed
      from a view of engineering. Particular emphasis is given to the analysis of the
      function and the position of traditional medical imaging modalities in the era of
      molecular imaging. Finally a discussion is made for the further development of
      medical imaging modalities along the line of molecular imaging.

PMID- 17552166
TI  - [A study on individual mandibular prostheses according to 3D reconstruction of CT
      images and CNC simulation method].
AB  - The new method of manufacturing individual mandibular prostheses, in combination
      with CT data and CNC technique, can duplicate bone tissues accurately, and can
      have the individual mandibular prosthesis made to order, and repair the
      mandibular defect (especially the lager mandibular segmental defect).

PMID- 17552167
TI  - [Tracheal reconstruction with memory alloy prosthesis coated with collagen].
AB  - OBJECTIVE: To investigate the feasibility of tracheal reconstruction with a
      prosthesis made of memory alloy coated with collagen sponge in mongrel dogs.
      METHOD: The basic skeleton of the prosthesis was knitted with Ni-Ti memory alloy
      wires. The tubular mesh was sealed with polyurethane membrane and then inner and
      external walls of the lumen were coated with collagen sponge. Cervical trachea
      segmental reconstruction was performed in 8 mongrel dogs with these prostheses.
      The efficacy of the implanted prostheses were periodically evaluated after
      operation using x-ray, tracheoscopy and specimen microscope examinations.
      RESULTS: One dog died of prosthesis dislocation 10 days after operation, another
      was killed 45 days later because of anastomotic stenosis. 6 dogs survived more
      than 90 days and the longest one lived for 150 days. Its implanted prosthesis was
      completely incorporated with the recipient tissue, where re-epithelialization
      occluded on anastomotic sites. The tracheal lumen was patent. CONCLUSION: This
      memory alloy tracheal prosthesis has been proved useful for reconstruction of
      large, circumferential tracheal defects, although its long-term safety and
      efficiency need to be confirmed.

PMID- 17552168
TI  - [Implementation of master patient index based on IHE PIX].
AB  - This paper introduces the PIX integration profile, a cross-referencing algorithm,
      an ID-merging algorithm and the master patient index (MPI) implementation based
      on the PIX integration profile.

PMID- 17552169
TI  - [A design of a portable acquistion system for autonomic nervous function data].
AB  - In this paper, a design of the portable acquisition system for autonomic nervous
      function data based on the microcontroller is introduced. The system contains an
      electrocardiogram amplifier and an AD convertor, using SD memory card as its
      storage device and thus it can record data for a longer time and exchange data
      with PC easily. The system with a simple structure realizes its miniaturization
      and low energy consumption.

PMID- 17552170
TI  - [Optimization of intra-vascular stent designs].
AB  - The finite element method introduced in this paper is used to simulate the
      expanded stents shapes and the whole expansion process of the stents with
      different designs, in order to calculate their radial displacements and
      deformation stress levels, thus to get the optimization of stent structural
      designs.

PMID- 17552171
TI  - [Considerations about the realization of DICOM-E-mail in China].
AB  - Considering the real conditions in China, the strategy and scheme of DICOM-E
      Mail's clinical applications in China are discussed in this paper.

PMID- 17552172
TI  - [Development of an intellectualized nursing & monitoring system in hospital
      wards].
AB  - This paper introduces an intellectualized nursing & monitoring system in hospital
      wards. The system has many functions, such as integrated collection of the
      clinical data, instant monitoring, intellectual control, automatic alarming and
      spoken intercom. It makes a breakthrough in the traditional models of manual
      collection of the clinical data and manual control over the speed of intravenous
      injection.

PMID- 17552173
TI  - [Progress in a research on biochip image analysis].
AB  - Microarray imaging is considered as an important tool for large scale analysis of
      gene expression. The accuracy of the gene expression depends on the experiment
      itself and further image processing. It's well known that the image analysis
      introduced during the experiment will greatly affect the accuracy of the gene
      expression. Microarray image analysis plays a potentially-arge impact on the gene
      detecting subsequent analysis (image segmentation, spot intensity and spot
      intensity extraction). In this paper, based on the characters of microarray
      images, the methods of microarray images' denoising and automatic-identification
      of the spot are reviewed.

PMID- 17552174
TI  - [An introduction of IHE].
AB  - This paper briefly introduces the history, definitions of some important words,
      working process, key concepts, connectathon testing, implementation of IHE, which
      can be regarded as an entry guide of IHE.

PMID- 17552175
TI  - [An introduction [corrected] of RID & XDS integration profiles].
AB  - In this article, 2 IHE integration profiles-RID integration profile and XDS
      integration profile, which are adopted widely in the applications of healthcare
      information exchange, are introduced and compared with each other in applicable
      occasions. In addition, their current developing status and prospects are give
      from the technical view.

PMID- 17552176
TI  - [Major problems existing in the supervision and administration of medical devices
      in China].

PMID- 17552177
TI  - [Dynamics of forest community structure and complexity in the process of
      secondary succession in bedrock area of west Shanxi Province].
AB  - In this paper, four plots representing the typical secondary succession stages of
      forest community were selected at the shady slope of bedrock area in Zhongyang
      County of West Shanxi, aimed to study the variation patterns of the structure and
      complexity of forest community in the process of secondary succession. The
      results showed that in the succession process of the community, there was an
      evident regularity in the variation of height and diameter class structure. The
      proportion of high and big individuals in the community increased gradually,
      while that of low and small ones increased first but decreased then. From the
      viewpoint of height class structure, the compositional complexity of tree species
      H (X), structural complexity of tree species H (Y/X), and complexity of whole
      community H (X,Y) all increased first, but decreased then with the succession. At
      the early, middle and arbor stages of succession, the H(X) value was 2.96, 3.85
      and 3.75, while H (Y/X) value was 1.27, 1.66 and 1.37, respectively.

PMID- 17552178
TI  - [Age estimation and age structure of Cycas fairylakea population in Shenzhen
      City].
AB  - Based on the structural characteristics of Cycas trunk, including vegetative leaf
      base scars, sporophyll concave rings, and average occurrence probabilities of
      vegetative leaf and sporophyll, a method for the age estimation of Cycas
      fairylakea population was developed, and the age of each individual was
      calculated. Three approaches, i.e., age structure diagram, age distribution curve
      and curve estimation were used to study the age structure of C. fairylakea
      population at genet and clone population levels. The age structure diagram showed
      that the clone population of C. fairylakea was stable, but the genet population
      was in declining. However, both of the clone and genet populations were in
      declining when using the other two approaches. It was considered that the C.
      fairylakea population was in declining, and needed an urgent protection.

PMID- 17552179
TI  - [Effects of tree species fine root decomposition on soil active organic carbon].
AB  - With incubation test, this paper studied the effects of fine root decomposition
      of Alnus cremastogyne, Cunninghamia lanceolata and Michelia macclurei on the
      content of soil active organic carbon at 9 degrees C , 14 degrees C , 24 degrees
      C and 28 degrees C. The results showed that the decomposition rate of fine root
      differed significantly with test tree species, which was decreased in the order
      of M. macclurei > A. cremastogyne > C. lanceolata. The decomposition rate was
      increased with increasing temperature, but declined with prolonged incubation
      time. Fine root source, incubation temperature, and incubation time all affected
      the contents of soil microbial biomass carbon and water-soluble organic carbon.
      The decomposition of fine root increased soil microbial biomass carbon and water
      soluble organic carbon significantly, and the effect decreased in the order of M.
      macclurei > A. cremastogyne > C. lanceolata. Higher contents of soil microbial
      biomass carbon and water-soluble organic carbon were observed at medium
      temperature and middle incubation stage. Fine root decomposition had less effect
      on the content of soil readily oxidized organic carbon.

PMID- 17552180
TI  - [Physico-chemical characteristics of ambient particles settling upon leaf surface
      of six conifers in Beijing].
AB  - The study on the density of ambient particles settling upon the leaf surface of
      six conifers in Beijing, the micro-configurations of the leaf surface, and the
      mineral and element compositions of the particles showed that at the same sites
      and for the same tree species, the density of the particles settling upon leaf
      surface increased with increasing ambient pollution, but for various tree
      species, it differed significantly, with the sequence of Sabina chinensis and
      Platycladus orientalis > Cedrus deodara and Pinus bungeana > P. tabulaeformis and
      Picea koraiensis. Due to the effects of road dust, low height leaf had a larger
      density of particles. The density of the particles was smaller in summer than in
      winter because of the rainfall and new leaf growth. The larger the roughness of
      leaf surface, the larger density of the particles was. In the particles, the
      overall content of SiO2, CaCO3, CaMg(CO3,), NaCl, 2CaSO4 . H2O, CaSO4 . 2H2O and
      Fe2O3 was about 10%-30%, and the main minerals were montmorillonite, illite,
      kaolinite and feldspar. The total content of 21 test elements in the particles
      reached 16%-37%, among which, Ca, Al, Fe, Mg, K, Na and S occupied 97% or more,
      while the others were very few and less affected by sampling sites and tree
      species.

PMID- 17552181
TI  - [Soil infiltration characteristics under main vegetation types in Anji County of
      Zhejiang Province].
AB  - The study on the soil infiltration under different main vegetation types in Anji
      County of Zhejiang Province showed that the characteristics of soil infiltration
      differed significantly with land use type, and the test eight vegetation types
      could be classified into four groups, based on soil infiltration capability. The
      first group, deciduous broadleaved forest, had the strongest soil infiltration
      capability, and the second group with a stronger soil infiltration capability was
      composed of grass, pine forest, shrub community and tea bush. Bamboo and
      evergreen broadleaved forest were classified into the third group with a
      relatively strong soil infiltration capability, while bare land belonged to the
      fourth group because of the bad soil structure and poorest soil infiltration
      capability. The comprehensive parameters of soil infiltration (alpha) and root
      (beta) were obtained by principal component analysis, and the regression model of
      alpha and beta could be described as alpha = 0. 1708ebeta -0. 3122. Soil
      infiltration capability was greatly affected by soil physical and chemical
      characteristics and root system. Fine roots (< or = 1 mm in diameter) played
      effective roles on the improvement of soil physical and chemical properties, and
      the increase of soil infiltration capability was closely related to the amount of
      the fine roots.

PMID- 17552182
TI  - [Simulation of crown leaf area index of Korean pine and broadleaved mixed forest
      in Chang-Bai mountains].
AB  - Based on the 3-year successive automatic measurement of photosynthetic active
      radiation above and under the crown of Korean pine and broadleaved mixed forest
      in Changbai Mountains, as well as the seasonal observation on leaf area index, a
      semi-empirical model was established to estimate the crown leaf area index of the
      forest. The results showed that this model could well reflect the seasonal
      variation of crown leaf area. From the comparison of 3-year leaf area index
      series, it was found that the date when the leaf area index began to rise was
      postponed if the date when its air temperature stably surpassed 0 degrees C came
      late. The dynamics of the leaf area index in whole growth season could be divided
      into three stages, i. e., rising, relatively stable, and dropping, and at each
      stage, there was a greater correlation between the leaf area index and the
      accumulated temperature above 0 degrees C, which could be expressed by Logistic
      curve and linear equation. The problems existing in the observation and
      estimation of forest crown leaf area index were discussed.

PMID- 17552183
TI  - [Effects of moss crust on soil seed bank at southeast edge of Tengger Desert].
AB  - An investigation was made on the soil seed bank at southeast edge of Tengger
      Desert with moss crust under natural and artificial vegetations. The results
      showed that the density of soil seed bank increased with the development of moss
      crust, which was 3.4 times higher under natural vegetation than under 24 years
      old artificial vegetation. In the seed bank, a total of 12 species belonging to 6
      families were identified, among which, annuals occupied more than 70%. No
      perennial seeds were found under artificial vegetation, but under natural
      vegetation, 20% of the seeds were of perennials. As for semi-shrub seeds, they
      occupied 20% and 10% under artificial and natural, vegetation, respectively.
      Under artificial vegetation, the species richness index of soil seed bank was
      relatively lower, being about a half of that under natural vegetation. The
      species diversity index of the seed bank had a slight decrease with the
      development of moss crust under artificial vegetation, but increased to the
      maximum (0. 693) under natural vegetation. The species similarity index was 1
      among the seed banks under artificial vegetations, and 0.4 between those under
      artificial and natural vegetation. The development of moss crust increased the
      roughness of surface soil and improved soil environment significantly, which
      could have positive effects on seed entrapment and plant establishment.

PMID- 17552184
TI  - [A isolation and identification of an antioxidant from Monochoria vaginalis].
AB  - With solvent extraction, a total of four fractions were separated from 75%
      alcohol extract of Monochoria vaginalis, and their antioxidative activities were
      measured by iodine method. The results showed that among the fractions, n-butanol
      fraction exhibited the highest antioxidative activity, which was not only
      significantly higher than CK (water), but also equivalent to the natural
      antioxidant tea polyphenols and synthetic antioxidant butylated hydroxyl toluene
      (BHT). A compound was isolated from the n-butanol fraction by using column
      chromatography, and identified as stigmasterol 3-O-beta-D-glucopyranoside. Its
      antioxidative activity estimated by the determination of the percentage of
      scavenged free radicals indicated that this compound exhibited a higher activity
      than BHT in scavenging free radicals.

PMID- 17552185
TI  - [Coupling effect of two drought-resistant agents on photosynthetic
      characteristics of Euonymus japonicus].
AB  - A field study on the coupling effect of new drought-resistant agents FA Handilong
      (FA HDL) and Beijing Green Angel (BGA) on the photosynthetic characteristics of
      Euonymus japonicus showed that these two agents could all decrease the stomatal
      conductance (gs) and transpiration rate (Tr) , and increase the net
      photosynthesis rate (Pn) and Pn/Tr of E. japonicus leaves. The inhibitory effect
      of FA HDL on gs and Tr was more significant when BGA was not applied. FA HDL
      inhibited the Pn and Pn/Tr when applied with BGA, but stimulated them when BGA
      was not applied. Applying BGA could obviously shorten the action period of FA HDL
      on E. japonicus. The fact that BGA could influence the effect of FA HDL was
      attributed to the properties of BGA and the photosynthetic characteristics of E.
      japonicus. The appropriate concentration of FA HDL to the E. japonicus without
      BGA application was 2 g x L(-1), and FA HDL was not appropriate to the E.
      japonicus applied with BGA.

PMID- 17552186
TI  - [Effects of free-air CO2 enrichment on nitrogen uptake and utilization of wheat].
AB  - In this paper, the effects of free-air CO2 enrichment (FACE) and its interaction
      with nitrogen supply on the nitrogen content, uptake, allocation, and use
      efficiency of winter wheat variety Ningmai 9 at its different growth stages were
      studied in 2001-2003. The results showed that under FACE treatment, the nitrogen
      content in wheat plant sampled at different growth stages all decreased
      significantly, with an average decrement of 4.4% to 13.4% compared with the
      control. The nitrogen accumulation under FACE increased significantly (9.2% 
      32.3%), and the increasing rate was larger at middle growth stage than at early
      and late growth stages. Nitrogen fraction was higher in stem, but lower in leaf.
      As for spike, the accumulation of nitrogen depended on the growth stage. FACE
      resulted in a significant increase (5.5% -10.3%) of nitrogen use efficiency for
      biomass production at all growth stages, of nitrogen harvest index (16.3%) at
      maturing stage, and of nitrogen use efficiency (9.3%) for grain yield. Nitrogen
      application increased the nitrogen content of wheat plant and its N uptake at all
      growth stages, decreased the nitrogen use efficiency, but had less effect on the
      nitrogen allocation in different organs.

PMID- 17552187
TI  - [Dynamic simulation on shoot dry matter partitioning and yield formation of
      rapeseed].
AB  - Based on the quantitative relationships between rapeseed growth and environmental
      factors, a simulation model was developed to estimate the shoot dry matter
      partitioning and yield formation of rapeseed. The dry matter partitioning indices
      of green leaf, stem and pod varied with the physiological development, and were
      influenced by the genotype, sowing date, nitrogen level and water status. Green
      leaf dry matter was regulated by nitrogen nutrition index (NNI). The higher the
      NNI, the higher the partitioning index of green leaf was. The factor of sowing
      date was introduced to regulate the partitioning index of pod. A delayed sowing
      date often induced an increased partitioning index of pod. The validation with
      different data sets involving variety, sowing date, and nitrogen application rate
      showed that this model had a good predictability and practicability.

PMID- 17552188
TI  - [Effects of silicon on photosynthesis and antioxidative enzymes of maize under
      drought stress].
AB  - With pot experiment, this paper studied the effects of silicon supply on drought
      resistance capability of maize plant. The results showed that under mild and
      severe drought stress, supplying silicon could increase the plant biomass by
      31.1%-33.3% and 23.7%-40.5%, respectively, compared with the control. Silicon
      enhanced the net photosynthetic rate by 10.9% --28.8%, increased the chlorophyll
      content and POD, SOD and CAT activities by 4.0% -11.9%, 6.4% -26.4%, 17.8% -26.8%
      and 3.2%-33.5%, respectively, and restrained the increase of leaf plasma membrane
      permeability and MDA content. Correlation analysis indicated that there was a
      significant correlation between plant dry matter accumulation and diurnal
      photosynthetic cumulates (r = 0. 9357, P < 0.05), demonstrating that the
      enhancement of photosynthesis under effect of silicon supply was the main factor
      inducing the increase of dry matter accumulation under drought stress. The higher
      antioxidative enzyme activities with silicon supply lightened the injury effect
      of free radicals, being another important factor inducing the increase of plant
      drought-resistance capability.

PMID- 17552189
TI  - [Effects of NaCl stress on the growth, antioxidant enzyme activities and reactive
      oxygen metabolism of grafted eggplant].
AB  - By the method of hydroponics and with the salt-tolerant eggplant cultivar 'Torvum
      Vigor' (Solanum torvum) from Japan as rootstock and the cultivar 'Suqiqie'
      (Solanum melongena L. ) as scion, this paper studied the differences between
      grafted and own-root seedlings in their photosynthetic characteristics,
      antioxidant enzyme activities, and reactive oxygen metabolism under 80 mmol x L(
      1) NaCl stress. The results showed that under NaCl stress, the dry mass,
      chlorophyll content and photosynthetic rate of grafted seedlings were 67.8%, 8.
      8% and 31.1% higher than those of own-root seedlings, respectively, and the
      antioxidant enzyme activities were significantly higher while the O2* producing
      rate and the hydrogen peroxide (H2O2) and malondiadehyde (MDA) contents were
      significantly lower in grafted seedlings leaves than in own-root seedlings. For
      both grafted and own-root seedlings, NaCl stress reduced the chlorophyll content
      and photosynthetic rate, but increased the O2* producing rate and the H2O2 and
      MDA contents significantly. However, the growth of grafted seedlings was less
      affected by NaCl stress. The stronger salt tolerance of grafted eggplant
      seedlings was related to their higher antioxidant enzyme activities and less
      oxidative damage.

PMID- 17552190
TI  - [Effects of exogenous betaine on physiological responses of peach tree under
      water stress].
AB  - With four-year-old potted Prunus persica L. cv. Qingfeng as test material, this
      paper studied the change pattern of its leaf betaine content under water stress,
      and its physiological responses under effects of foliage-spraying exogenous
      betaine. The results showed that under normal water supply, the betaine content
      in Qingfeng' s leaf was 75.9-80.5 microg x g(-1) FM, which was increased with
      increasing water stress, and up to 278.9 microg x g(-1) FM on the 16th day after
      cutting off the water supply. The leaf plasma membrane permeability was 8.06% -
      8.61% under normal water supply, but increased to 28.62% under water stress. When
      100 and 500 mg x L(-1) of betaine were applied exogenously, the plasma membrane
      permeability was 26.25% and 21.79% after 16 days, respectively. The hydrogen
      peroxide (H2O2) content increased from 27.2-32.5 micromol g(-1) FM to 76.4
      micromol x g(-1) FM in the course of water stress, and decreased to 73.2 and 68.5
      micromol x g(-1) FM after spraying 100 and 500 mg betaine x L(-1), respectively.
      During the period of intensified water stress, the peak value of ascorbate
      peroxidase (AsA-POD) activity was 0.435 mg x g(-1) FM, and up to 0.490 mg x g(-1)
      FM when treated with exogenous betaine. When the peach tree was subjected to
      water stress, the contents of free proline and soluble sugar accumulated
      dramatically, but produced on approximately decrease in 500 mg x L(-1) endogenous
      betaine application on the 16th day which was slightly less than that of control
      and 100 mg x L(-1) betaine application. There was a gradual decline in the
      content of soluble protein under water stress, and an increment of 20. 3% was
      observed when betaine was applied exogenously. These results strongly suggested
      that foliage-spraying exogenous betaine could increase the drought resistance of
      peach tree through decreasing its leaf plasma membrane permeability and H2O2,
      free proline and soluble sugar contents and increasing its leaf AsA-POD activity
      and soluble protein content.

PMID- 17552191
TI  - [Changes in diversity of culturable microorganisms on leaf surface of transgenic
      Bt cotton].
AB  - In a field study, the quantitative changes of bacterial, actinomycetic and fungal
      populations on the leaf surface of transgenic Bt cotton (GK-12) and non
      transgenic Bt cotton (Simian No. 3) were monitored at seedling, squaring,
      flowering and boll-opening stages, respectively, and the diversity of bacterial
      physiological groups was analyzed at flowering and boll-opening stages. The
      results showed that there was a positive correlation between the quantity of
      culturable microorganisms and the development of cotton. The total number of
      bacteria, fungi and actinomyces began to rise at seedling stage, reached its peak
      at flowering stage, and decreased markedly at boll-opening stage. The Simpson
      index, Shannon-Wiener index, and evenness index of bacterial physiological groups
      were higher at flowering stage, but lower at boll-opening stage on GK-12 than on
      Simian No. 3.

PMID- 17552192
TI  - [Isolation, identification and field control efficacy of an endophytic strain
      against tobacco bacterial wilt (Ralstonia solanacarum)].
AB  - In this paper, an endophytic strain B-001 against tobacco bacterial wilt
      (Ralstonia solanacarum) was isolated from the stem of healthy tobacco in R.
      solanacarum-infected fields, which had a stronger inhibitory effect on some kinds
      of gram-positive bacteria, gram-negative bacteria, and pathogenic fungi. This
      strain belonged to Bacillus, and its 16S rDNA after PCR and sequencing had an
      accession of GenBank being DQ444283. The 16S rDNA phylogenetic tree was
      constructed with MEGA3, and compared with the published 16S rDNA sequences of
      relative bacteria species. B-001 had a 99.2% sequence similarity with Bacillus
      subtilis (DQ415893). According to the morphological, physiological and
      biochemical characteristics, and based on phylogenetic analysis, B-001 was
      identified as a strain of B. subtilis. Field experiments in Guiyang and Ningxiang
      counties of Hunan Province showed that in 2005 and 2006, the control efficacy of
      B-001 on R. solanacarum ranged from 40.03% to 78. 14%, better than that of
      Streptomycini.

PMID- 17552193
TI  - [Effects of root exudates from cucumber and squash on fusarium wilt occurrence].
AB  - With the root exudates of two cucumber varieties Jinyan 4 (susceptible variety)
      and Jinchun 4 (resistant variety) and of black seed squash variety as test
      materials, this paper studied their effects and action mechanisms on the
      occurrence of Fusarium wilt on Jinyan 4. The results showed that the occurrence
      of Fusarium wilt was earlier when treated with the root exudates of Jinyan 4, and
      the infection rate was significantly higher at 15 days after inoculation, but
      nearly the same as the control at 20 days after inoculation. On the contrary, the
      infection rate was significantly lower than the control when treated with the
      root exudates of Jinchun 4. The plant height and fresh mass of Jinyan 4 treated
      with its own root exudates were lower than those of the control, and the root
      vigor decreased but conductance increased. No significant effect was observed in
      the plant height and fresh mass of Jinyan 4 treated with the root exudates of
      Jinchun 4 and black seed squash. It could be concluded that the root exudates of
      susceptible cucumber variety stimulated the growth of Fusarium oxysporum
      pathogen, while those of resistance cucumber variety and black seed squash were
      in adverse.

PMID- 17552194
TI  - [Molecular evaluation on the efficacy of sustainable control of Monochamus
      alternatus by non-woven fabric fungal bands impregnated with Beauveria bassiana].
AB  - By using molecular marker of group I intron, a field evaluation was made on the
      efficacy of sustainable control of Monochamus alternatus by non-woven fabric
      bands impregnated with Beauveria bassiana. The results showed that the control
      efficacy in two treated plots was 19.5% and 10.8%, and 14.2% and 11% when
      evaluated with conventional and molecular evaluation methods, respectively,
      suggesting that the conventional method which evaluated the control efficacy in
      terms of microbes mortality or infection rate couldn't distinguish the efficacies
      caused by released biocontrol agents and indigenous pathogens, while molecular
      method could avoid the interference of indigenous pathogens and give an objective
      and reasonable evaluation on the efficacy of microbial control.

PMID- 17552195
TI  - [Landscape change and its spatial driving force of farmlands in Wenchuan County
      of Min-jiang River upper reach].
AB  - Based on remote sensing images and geographic information system, and by using
      landscape metrics and Kappa coefficient, this paper studied the farmland
      landscape change in Wenchuan County of Minjiang River upper reach. A logistic
      regression model was used to analyze the driving forces of this change, with
      elevation, gradient, aspect, and the distances to road, river and settlement as
      the affecting factors. The results showed that from 1974 to 2000, the farmland
      area in Wenchuan County kept increasing, with the greatest increment in 1974
      1986. In 1986-2000, farmland area had no evident increase, but converted with
      other landscape types frequently and had an evident spatial position change,
      especially in the period from 1994 to 2000. Such a farmland change was mainly
      driven by policy, and the spatial driving forces differed in different periods.

PMID- 17552196
TI  - [Remote sensing estimation of vegetation coverage in guangzhou based on the
      correction of atmospheric radiation].
AB  - Vegetation coverage is a basic parameter in describing landscape ecosystem, and
      an important index in assessing ecosystem health and security. Based on the four
      TM images in 1990, 1995, 2000 and 2005, and by using the correction model to
      deduct atmospheric radiation effect and the spatial operating model for TM image
      under unsupervised classification, the relationship model between vegetation
      coverage and normalized vegetation index was established, and the vegetation
      coverage in different phases in Guangzhou was calculated. The results showed that
      the vegetation coverage in Guangzhou decreased continuously from 1990 to 2000 but
      began to increase thereafter, which accorded with the economic development and
      environmental construction of the city. The model established in this paper could
      simulate well the dynamics of regional vegetation cover, and have the advantage
      in describing the dynamics of vegetation coverage more accurately, being
      available to the assessment of urban eco-environmental quality and its dynamic
      characters.

PMID- 17552197
TI  - [Temporal and spatial variation of MODIS vegetation indices in Hunan Province].
AB  - Based on MODIS images and by using the algorithm of maximum value composite
      (MVC), the monthly vegetation indices (VIs) in 2005 in Hunan Province were
      obtained. Through the analysis of the MODIS VIs, Hunan Province was divided into
      six districts to describe the spatial distribution of the VIs, and by using the
      monthly mean temperature and rainfall data collected from 5 climatic monitoring
      stations in this province, the temporal variation of the VIs was analyzed. The
      results showed that the spatial distribution of MODIS VIs was positively
      correlated with vegetation cover, and appeared regional characteristics. The
      MODIS VIs varied with season, and the curves of their monthly mean values were
      downwards opening quadratic parabolas, with the maximum appeared in July. The
      value of MODIS EVI was smaller than that of MODIS NDVI. MODIS VI was mainly
      affected by monthly mean temperature, but this effect was decreased with
      decreasing latitude. The variation pattern of MODIS EVI was more apparent than
      that of MODIS NDVI, i. e. , the quadratic parabola of MODIS EVI was smoother,
      going gradually from minimum to maximum and then going down, while that of MODIS
      NDVI had tiny fluctuations on both sides of the maximum point.

PMID- 17552198
TI  - [Measurement and dynamic analysis of ecological capital of terrestrial ecosystem
      in China].
AB  - Based on remote sensing and ecological principles, an estimation model of
      ecological capital was established in this paper. The estimation showed that the
      ecological capital of terrestrial ecosystem in China was 8.148, 10.86 and 12.44
      trillion yuan (RMB) in 1992, 1995 and 2000, respectively. Forest had the highest
      value (24 673 yuan x hm(-2)), and followed by wetland (21 353 yuan x hm(-2)),
      both of which gave the most contribution to the ecological capital. According to
      its spatial distribution, the ecological capital of terrestrial ecosystem in
      China descended from east to west, and ascended from middle to northeast and
      south of this country, which was accordant with the vegetation distribution.
      Owing to the climate change and human activity, the ecological capital of Chinese
      terrestrial ecosystem ascended from 1992 to 2000, and the spatial distribution of
      its largest value moved obviously from north to south, with a total change rate
      of about 20%. However, the ratio between ecological capital and GDP descended
      significantly in the 1990s.

PMID- 17552199
TI  - [Theoretical model for rocky desertification control in karst area].
AB  - Based on the basic principles of restoration ecology, the trigger-action model
      for rocky desertification control was proposed, i. e. , the ability that an
      ecosystem enables itself to develop was called dominant force, and the
      interfering factor resulting in the deviation of the climax of ecological
      succession from its preconcerted status was called trigger factor. The ultimate
      status of ecological succession was determined by the interaction of dominant
      force and trigger factor. Rocky desertification was the result of serious
      malignant triggers, and its control was the process of benign triggers in using
      the ecological restoration method of artificial designs to activate the natural
      designing ability of an ecosystem. The ecosystem of Karst rocky desertification
      in Fenghuang County with restoration measures was taken as a case to test the
      model, and the results showed that the restoration measures based on trigger
      action model markedly improved the physical and chemical properties of soil and
      increased the diversity of plant. There was a benign trigger between the
      restoration measures and the Karst area. The rationality of the trigger-action
      model was primarily tested by the results in practice.

PMID- 17552200
TI  - [Heavy metals removal and its kinetics in contaminated soil under effects of EDTA
      washing].
AB  - In this paper, batch experiments were made to examine the effects of different
      EDTA concentrations, pH, and washing duration of EDTA on the removal of heavy
      metals from contaminated soil. An empirical model was employed to describe the
      kinetics of heavy metals dissolution and desorption, and the form changes of test
      heavy metals were determined before and after EDTA washing. The results showed
      that EDTA was effective to the removal of heavy-metals from contaminated soil. At
      0.1 mol x L(-1) and pH 7 of EDTA and within 24 h, the removal rate of test heavy
      metals was the maximum, being 89.14% for Cd, 34.78% for Pb, 14.96% for Cu, and
      45.14% for Zn. The mass transfer coefficient was in the order of Cd > Zn > Pb >
      Cu. Sequential fractionations of treated and untreated soil samples showed that
      EDTA was effective in removing the exchangeable, carbonate and oxide forms of Cd,
      Pb, Zn and Cu, but ineffective for the organic and residual forms of test heavy
      metals.

PMID- 17552201
TI  - [Microbiological characteristics of phytoremediation plant root-soil interface
      for petroleum contaminated soil].
AB  - With the petroleum-contaminated soil under Ricinus communis L. phytoremediation
      in Shenfu irrigation area of Shenyang as test material, this paper studied the
      quantitative variations of bacteria and fungi, physiological and biochemical
      characteristics of dominant microbial species, and nutritional types of bacteria
      in root zone, rhizosphere, root plane and root inside. The results showed that
      the quantity of bacteria decreased in the order of rhizosphere > root plane >
      root inside, while that of fungi was in the sequence of root inside > root plane
      > rhizosphere. The dominant species of bacteria and fungi were most abundant in
      root plane and root inside, respectively, and the dominant bacterial species in
      root plane and root inside had a stronger capability in degrading macro-molecular
      substances. The nutritional demand of bacteria in root plane was of amino acid
      type.

PMID- 17552202
TI  - [Effects of solution pH and simulated acid rain on the behavior of two
      sulfonylurea herbicides in soil].
AB  - By the methods of batch equilibration and leaching, this paper studied the
      effects of solution pH and simulated acid rain on the behavior of bensulfuron
      methyl and metsulfuron-methyl in soil. The results showed that the adsorption
      isotherms of these two herbicides fitted Freundlich equation well, and their
      adsorbed amounts reduced obviously with the increasing pH of water-soil system,
      which in turn promoted the translocation of the herbicides in soil. The
      adsorption coefficient (Kf) was positively correlated with soil organic matter
      and clay contents, while negatively correlated with soil pH. The higher pH of
      simulated acid rain had a greater contribution on the leaching of the two
      sulfonylurea herbicides, and their leached amount was increased with increasing
      acid rain. There was a close relationship between the leaching of the herbicides
      and the properties of soil. The soils with higher contents of organic matter and
      clay had a greater retention capability to the herbicides.

PMID- 17552203
TI  - [Effects of Hg on soil enzyme activity].
AB  - With simulation test, this paper studied the effects of Hg on the activities of
      urease, invertase and neutral phosphotase in four soils. The results showed that
      Hg inhibited soil urease and invertase activities markedly, but its inhibitory
      effect differed with test soils. There was a significant logarithmic correlation
      between the concentration of HgCl2 and the activities of these two enzymes (P <
      0.05). In test soils, the ED50 of urease activity was 87.99, 5.47, 24.05 and
      19.88 mg x kg(-1), and that of invertase activity was 76.68, 727.49, 236.52 and
      316.59 mg x kg(-1), respectively. Urease was more sensitive than invertase to Hg
      contamination, while organic matter had a protective effect on soil enzymes. Soil
      neutral phosphatase was not sensitive to Hg contamination, except that it was
      significantly activated by Hg in the meadow brown soil applied with plenty of
      organic fertilizer.

PMID- 17552204
TI  - [Cu and Pb absorption and tolerance of Agrostis stolonifera and Festuca
      arundinacea].
AB  - This paper studied the seed germination rate, chlorophyll content, net
      photosynthetic rate, SOD activity, and Cu and Pb absorption of Agrostis
      stolonifera and Festuca arundinacea under Cu and Pb pollution. The results showed
      that Cu and Pb pollution had a significant effect on the seed germination rate of
      F. arundinacea. The chlorophyll content of F. arundinacea decreased dramatically
      under Pb and Cu-Pb pollution, while decreased slightly under Cu pollution. No
      significant effect of Cu and Pb was observed on the chlorophyll content of A.
      stolonifera. The SOD activity of A. stolonifera increased under 350 mg Cu x kg(
      1) and all test concentrations of Pb, while that of F. arundinacea only increased
      under 700 mg Pb x kg(-1) and 350 mg Cu x kg(-1) + 1100 mg Pb x kg(-1). The net
      photosynthetic rate of F. arundinacea decreased more under Pb pollution than
      under Cu pollution, but that of A. stolonifera all decreased under Cu or Pb
      pollution. It was suggested that A. stolonifera was more tolerant in
      physiological characteristics to Cu and Pb pollution than F. arundinacea, while
      F. arundinacea was more tolerant to Cu than to Pb. The Cu absorption amount of F.
      arundinacea was relatively large, but did not increase with increasing Cu
      pollution. A. stolonifera had a high absorption ability of Pb, and the absorbed
      Pb amount was increased with increasing Pb pollution. A. stolonifera and F.
      arundinace could be the potential phytoremediation plants for Pb and Cu-polluted
      soil, respectively.

PMID- 17552205
TI  - [Limiting factors of waste land revegetation in indigenous zinc smelting areas of
      western Guizhou].
AB  - With indigenous zinc smelting waste residue, contaminated soil and background
      soil as test substrates, a pot experiment was conducted to study the growth
      characteristics of Lolium perenne and Trifolium pretense on these substrates. The
      results showed that the major limiting factors of waste land revegetation in
      indigenous zinc smelting areas of western Guizhou were the salt-alkali stress and
      the lower contents of organic matter, total N, available N and total K. The heavy
      metals in waste residue had a high concentration, but their available forms only
      occupied a small proportion, with low toxicity to plant but having potential
      harmful risk. Contaminated soil had lower concentrations of heavy metals than
      waste residue, but its contained heavy metals were more in available form. The
      constraints of revegetation on contaminated soil were the toxicity of heavy
      metals and the low contents of available P and K. Mixing contaminated soil with
      zinc smelting waste residue could be one of the effective approaches for the
      substrate amendment in indigenous zinc smelting areas.

PMID- 17552206
TI  - [Effects of co-substrates on biodegradation of pyrene by ten bacterial strains].
AB  - A total of 10 bacterial strains represented as from SB01 to SB10 were isolated
      from a petrolium-contaminated sludge, and their potential of degrading pyrene
      (PYR) was investigated on the substrates pyrene (MS1) , pyrene plus glucose
      (MS2), and pyrene plus phenanthrene (MS3). The results showed that on MS1, the
      degradation rate of PYR by SB01 was the highest, with 30.4% of PYR degraded after
      5 days. On MS2, the degradation rate of PYR by SB09 was the highest, being 37.7%
      after 5 days, while on MS3, 50.2% of PYR was removed by SB01. The degradation of
      PYR by SB01 and SB03 was inhibited by glucose, which was more obvious for SB01,
      but no significant difference was observed among SB02, SB07, SB08 and SB10. The
      biodegradation rate of PYR by all the ten bacterial strains was enhanced on MS3,
      and that by SB10 was increased by 29.8%. For SB04 and SB09, the biodegradation
      rate of PYR had no significant difference between MS1 and MS2, but for other
      strains, the stimulation effect of phenanthrene on PYR degradation was higher
      than that of glucose.

PMID- 17552207
TI  - [Photosynthetic responses of wheat and pea seedlings to enhanced UV-C radiation
      and their resistances].
AB  - With wheat and pea seedlings as test materials, this paper studied the effects of
      UV-C radiation on their leaf photosynthetic characteristics and antioxidant
      enzyme activities. The results showed that enhanced UV-C radiation could markedly
      decrease the photosynthetic rate (Pn) , stomatal conductance (Gs), intercellular
      CO2 concentration (Ci), transpiration rate (Tr) and carboxylation efficiency (CE)
      of pea leaves, but for wheat leaves, these parameters were increased first and
      decreased then. Under UV-C condition, the CO2 compensation point of leaf was
      increased for pea, but decreased first and increased then for wheat. With the
      increasing duration of UV-C radiation, the antioxidant enzyme activities of both
      test plants increased first and decreased then, except that the POD activity of
      pea and SOD activity of wheat decreased gradually. All of these suggested that
      wheat had a stronger resistance to short-time UV-C radiation than pea, but, with
      the prolonged duration of UV-C radiation, the photosynthesis and antioxidant
      enzyme activities of wheat and pea were all decreased.

PMID- 17552208
TI  - [Decay of genetically engineered microorganisms (GEMs) in activated sludge and
      its related affecting factors].
AB  - With batch experiment and continuous-running bioreactor, this paper studied the
      decay of the population size of genetically engineered microorganisms (GEMs) in
      activated sludge. The decay models and their parameters were obtained, and
      several affecting factors were analyzed. The results showed that both in batch
      experiment and in continuous-running bioreactor, the population size of the GEMs
      decreased rapidly initially, and then tended to keep constant. The dynamics of
      decay could be fitted well by Logistic model and Gompertz model, and no
      difference was observed between the fit goodness of the models. Under different
      conditions, the value ranges of the parameters in batch experiment were decay
      coefficient r' = 0.5-0.6 h(-1) and stable population size K' = 10(4) - 10(5) cfu
      x ml(-1) for Logistic model, and initial decay coefficient b = 0.6-1.2 h(-1) and
      specific decay coefficient a = 0.02-0.09 h(-1) for Gompertz model. The initial
      population size had a little effect on the decay, but affected stable population
      size remarkably. Mixed liquor suspended solid (MLSS) and temperature both
      affected remarkably, i. e., the decay became faster but got larger when MLSS was
      smaller, whereas the decay became faster and got smaller when temperature was
      lower. Nutrient conditions and predation by protozoa and metozoa were also the
      important affecting factors of decay. In continuous-running membrane bioreactor
      and conventional activated sludge reactor, Logistic model could also fit the
      dynamics of decay well, and the values of parameters were in the ranges obtained
      from batch experiment.

PMID- 17552209
TI  - [Soil moisture and interspecific relationships between grass and legume on mixed
      grassland: a research review].
AB  - From the viewpoints of plant morphology and physiology, this paper discussed the
      survival strategy of grass and legume on mixed grassland under water stress,
      their competition for water and the hydraulic facilitation effects of legumes on
      water resource utilization, and the impact of drought on biological nitrogen
      fixation and nitrogen transfer of legume. It was indicated that to promote the
      productivity of grassland in arid area, the mechanisms of competition and
      coexistence between grass and legume should be further studied, and one of the
      main aspects should be the effects of water stress on their aboveground and
      belowground competitions and their feedback on the competitions.

PMID- 17552210
TI  - [Effects of CO2 enrichment on grain quality of rice and wheat: a research
      review].
AB  - Crop grain quality is mainly depended on variety's genetic characteristics and
      environmental conditions, while elevated CO2 concentration in atmosphere, one of
      the main factors resulting in global climate change, would have a significant
      effect on crop grain quality. In this paper, the research progress on the effects
      of CO2 enrichment on rice and wheat grain quality was summarized from the aspects
      of protein and nitrogen contents, trace elements, and other characters,
      emphasized the necessity and urgency of the study in this field, and pointed out
      the key directions and contents of further study, i.e., (a) direct effects of CO2
      enrichment on rice and wheat grain quality and their differences for different
      varieties, (b) integrated effects of CO2 enrichment and other climate factors on
      rice and wheat grain quality and their quantitative indices, (c) action
      mechanisms of CO2 enrichment and other climate factors on rice and wheat grain
      quality formation, (d) longterm directions and strategies of rice and wheat
      breeding in quality improvement to adapt climate change, (e) integrated planting
      technology systems in quality improvement for adapting climate change, and (f)
      application of molecule-marker and gene-transfer in rice and wheat breeding for
      quality improvement.

PMID- 17552211
TI  - [Research advances in water-fertilizer effect on dry land farmland].
AB  - Water and fertilizer are the keys in improving dry land productivity, and the
      main factors limiting the agricultural development in dry land regions. For our
      food security and agricultural sustainable development, it' s of significance to
      bring the effect of water and fertilizer on increasing yield into full play. This
      paper introduced the design principles of several commonly used methods in
      researching the effect of water and fertilizer, e.g., irrigation experiment,
      rainproof-shed experiment and long-term experiment, compared their advantages and
      disadvantages, and discussed the mechanisms and models of water-fertilizer
      interaction on dry land farmland, based on the sum-up of the achievements of
      related qualitative and quantitative researches. It was indicated that under
      appropriate conditions, there was a positive interaction between water and
      fertilizer on grain yield, but the effect differed with research method and
      natural condition. The development trend of the researches on the water
      fertilizer effect on dry land farmland in light of the characteristics of agro
      ecosystern was also prospected.

PMID- 17552212
TI  - [Principles and methodology for ecological rehabilitation and security pattern
      design in key project construction].
AB  - Global ecological security becomes increasingly important with the intensive
      human activities. The function of ecological security is influenced by human
      activities, and in return, the efficiency of human activities will also be
      affected by the patterns of regional ecological security. Since the 1990s, China
      has initiated the construction of key projects "Yangtze Three Gorges Dam",
      "Qinghai-Tibet Railway", "West-to-East Gas Pipeline", "West-to-East Electricity
      Transmission" and "South-to-North Water Transfer" , etc. The interaction between
      these projects and regional ecological security has particularly attracted the
      attention of Chinese government. It is not only important for the regional
      environmental protection, but also of significance for the smoothly
      implementation of various projects aimed to develop an ecological rehabilitation
      system and to design a regional ecological security pattern. This paper made a
      systematic analysis on the types and characteristics of key project construction
      and their effects on the environment, and on the basis of this, brought forward
      the basic principles and methodology for ecological rehabilitation and security
      pattern design in this construction. It was considered that the following issues
      should be addressed in the implementation of a key project: 1) analysis and
      evaluation of current regional ecological environment, 2) evaluation of
      anthropogenic disturbances and their ecological risk, 3) regional ecological
      rehabilitation and security pattern design, 4) scenario analysis of environmental
      benefits of regional ecological security pattern, 5) re-optimization of regional
      ecological system framework, and 6) establishment of regional ecosystem
      management plan.

PMID- 17552213
TI  - [Research progress on wetland ecosystem service and its valuation].
AB  - With the recognition on the significance of wetland, wetland ecosystem service
      was come under more and more attention, and its valuation could give the
      policymakers a scientific support in punishing wetland destroyers and
      compensating its losers. This paper introduced the definitions of wetland
      ecosystem service, its function and value, summarized their valuation approaches,
      including market value approach, production function method, opportunity cost
      approach, shadow project approach, productivity variety approach, human capital
      approach, travel cost approach, hedonic value approach, contingent value approach
      and ecological value approach, and discussed the factors affecting the valuation
      results of these approaches as well as the existing problems in related
      researches. The further research directions in these fields were also prospected.

PMID- 17552214
TI  - [Process, mechanism, and research method of fish invasion].
AB  - Fish invasion has become a serious environmental and economic damage, and
      obtained a priority concern by the conservation ichthyologists and land managers.
      A better understanding of the invasive mechanisms is of significance in
      developing ecological theories and in controlling exotic pests. In this paper,
      the progress in studying the mechanisms of fish invasion was reviewed, involving
      the biological characteristics of exotic fish, their adaptive evolution,
      interactions among exotic and indigenous fish, and relationships between species
      diversity and community resistance to invasion, etc. The study of invasive
      process and the progress of research methods were discussed.

PMID- 17552215
TI  - [Effects of intercropping peanut with medicinal plants on soil microbial
      community].
AB  - With pot experiment, this paper studied the quantitative variations of bacteria,
      actinomyces, mould and yeast in soils of peanut intercropped with medicinal
      plants, aimed to test if such an intercropping pattern could remove the obstacles
      of peanut's continuous cropping. The results showed that Atractylodes lancea and
      Euphorbia pekinensis had the strongest inhibitory effect on mould. Compared with
      CK (mono-cropping peanut), the CFU of mould in the treatments intercropped with
      A. lancea and E. pekinensis was decreased by 53.87% and 29.59%, respectively
      during flowering-pegging stage of peanut, but increased after harvesting, which
      was in favor of substance circulation and nutrient returning. The CFU of bacteria
      in treatments intercropped with A. lancea, E. pekinensis and Pinellia ternate was
      all increased, and that of yeast in all five intercropping treatments was
      increased during the flowering-pegging stage of peanut. No familiar pathogens
      were found in the treatments intercropped with A. lancea, E. pekinensis and
      Diosoren zingiberebsis. Peanut intercropped with medicinal plants could regulate
      soil microbial community effectively.

PMID- 17552216
TI  - [Effects of starvation and re-feeding on carbohydrate metabolism of Marsupenaeus
      japonicus].
AB  - This paper studied the variations of glucose concentration in haemolymph and
      glycogen concentration in hepatopancreas and muscle of Marsupenaeus japonicus
      under starvation and re-feeding. Groups C, S1, S2 and S3 were deprived of food
      for 0, 10, 15 and 25 days, respectively, and then re-fed for 10 days. Under
      starvation, the glucose concentration in haemolymph and glycogen concentration in
      hepatopancreas decreased rapidly at the beginning, and the glycogen concentration
      in muscle was the lowest after 10-day fasting. In the following 5 days, the
      glucose concentration in haemolymph and glycogen concentration in hepatopancreas
      and muscle recovered to their initial levels due to gluconeogenesis, but the
      glycogen concentration kept declining with fasting. After refeeding, the glycogen
      concentration in hepatopancreas and muscle recovered well, and the glucose
      concentration in haemolymph had a sharper increase in groups S1 and S2 than in
      group C, but was markedly less in group S3 than in group C. These results
      indicated that long-term starvation had a greater effect on the glucose
      concentration in haemolymph.

PMID- 17552217
TI  - [Relationships between host preference of Liriomyza huidobrensis (Blanchard) and
      nutrient and chlorophyll contents in host foliage].
AB  - The laboratory study with no free choice means showed that the host preference of
      Liriomyza huidobrensis (Blanchard) adult differed significantly with test plants.
      Phaseolus vulgaris, Chrysanthemum coronarium and Cucurbita pepo were the most
      preferred, while Lycopersicum esculenturn and Brassica oleracea were the least.
      Correlative analysis indicated that the host preference of L. huidobrensis adult
      had a significant positive correlation with the content of soluble sugar, but
      less correlation with soluble protein and chlorophyll contents in host foliage.

PMID- 17552218
TI  - [Construction of Corynebacterium glutamicum/E. coli shuttle promoter-probe
      vector].
AB  - Based on the replication origins of the C. glutamicum pXZ10145 and the
      Escherichia coli ColE1 plasmid, a novel Corynebacterium glutamicum/Escherichia
      coli shuttle vector pAK6 was constructed. This vector was able to replicate in C.
      glutamicum and E. coli. Plasmid pAK6 carried multiple cloning site useful for
      gene cloning, kanamysin- and ampicillin-resistance-encoding gene. Furtherly based
      on the shuttle vector pAK6, a promoter-probe vector was developed for the
      isolation of promoter elements from C. glutamicum . This vector carried the
      promoterless chloramphenicol acetyltranstersae (CAT) gene as a reporter
      downstream from useful cloning site. For testing this promoter-probe vector, C.
      glutamicum genomic DNA was digested to completion with Sau3AI and the fragments
      shot-gun cloned into its unique Bgl II. Two fragments exhibiting promoter
      activity were isolated. By measuring CAT activity, the strength of promoter
      fragments was assayed. After being sequenced, promoter sequences were predicted
      by using BDGP Neural Network Promoter Prediction V2.2 and the similarities to the
      regions of the consensus promoter sequence or the known promoters were confirmed.

PMID- 17552219
TI  - [Attenuation of a genotype VIId Newcastle disease virus ZJI strain of goose
      origin by reverse genetics].
AB  - Based on the complete genome sequence of Newcastle disease virus (NDV) ZJI strain
      isolated from an outbreak in the goose, seven pairs of primers were designed to
      amplify cDNA fragment for constructing the plasmid pNDV/ZJI, which contained the
      full-length cDNA of NDV ZJI strain. The pNDV/ZJI with three helper plasmids, pCI
      NP, pCI-P and pCI-L, were then cotransfected into BSR-T7/5 cells expressing T7
      RNA polymerase. After inoculation of the transfected cell culture supernatant
      into embryonated chicken eggs from specific-pathogen-free (SPF) flock, infectious
      NDV ZJI strain was successfully rescued. The recombinant plasmid pNDV/ZJIFM was
      generated by converting the multi-basic amino acid sequence of the F0 protein
      cleavage region in pNDV/ZJI to the non-basic amino acid sequence characteristic
      of avirulent NDV strain. After cotransfection of the resultant plasmid and the
      three helper plasmids into BSR-T7/5 cells, the recombinant NDV, NDV/ZJIFM, was
      generated. The mean death time (MDT) of NDV/ZJIFM was more than 120h and the
      intrancerebral pathogenicity index (ICPI) was 0.16, indicating that the rescued
      virus was highly attenuated. This attenuated genotype VIId NDV of goose origin
      could be a desirable vaccine in controlling the current epidemic of ND.

PMID- 17552220
TI  - [Seven kinds of new SCCmec type in Methicillin-resistant Staphyloccus aureus and
      their susceptibility to the antibiotics].
AB  - In order to explore the resistance and the staphylococcal chromosome cassette mec
      (SCCmec) types of Methicillin-resistant S. aureus (MRSA) in the area of Haikou,
      686 strains of MRSA had been distinguished from 1174 strains of S. aureus using
      PBP2a testing. The resistance to the seven deputies of seven kinds antibiotics
      which in common use in clinic, including Oxacillin, Vancomycin, Doxycyclin,
      Amikacin, Erythromycin, Chloramphenicol, Ciprofloxacin, and SCCmec type of 58
      strains had been tested using the K-B Agar diffuse, E-test and multiplex PCR
      strategy, and seven kinds of new SCCmec types were found in 17 strains. Their
      specialties of structure are: type-new3 possess four loci of A, F, H, M; New4
      possess three loci of F, H, M; New5 possess three loci of D, B, M; New6 possess
      three loci of A, B, M; New7 possess four loci of H, E, C, M; New8 possess two
      loci of A, M; New9 possess three loci of A, C, M. All of them are different from
      the types reported. The strains carrying new SCC mec types are different from
      that carrying old SCC mec types in the epidemical distribution and resistance to
      the antibiotics: they were mostly isolated from the out-patients and have high
      level and wider range of resistance to antibiotics and deserve to pay more
      attention.

PMID- 17552221
TI  - [Cloning, sequencing and fuctional study of gacA gene from Xanthomonas oryzae pv.
      oryzicola].
AB  - A gacA homologue, designated gacA(Xooc), was cloned from Xanthomonas oryzae pv.
      oryzicola (Xooc), a bacterium that causes leaf streak of rice, with degenerated
      primers by polymerase amplification reaction (PCR). NCBI blast search indicated
      that GacA(Xooc) had a similar structure to that of other GacA proteins, and had a
      CheB (Chemotaxis response regulator containing a CheY-like receiver
      domain)domain. Sequence comparison showed that the gacA(Xooc) was conserved in
      the Xanthomonas genus. Homology search revealed that the gacA(Xooc) was 99.7%
      similarities to gacA (AY870457, this lab) of Xanthomonas oryzae pv. oryzae (Xoo).
      A gacA(Xooc), disruption mutant was successfully generated by a single cross-over
      event, and confirmed by PCR and Southern blot. But the mutant still had strong
      pathogenicity,and its virulence was not obviously different from that of wild
      type strain. The gacA did not globally regulate metabolism in Xooc, which was
      different from DC3000 of P. syringae pv. tomato, CHAO of P. fluorescens and
      IC1270 of Serratia plymuthica. Chemotaxis to 0.1% tryptone of the mutants was
      reduced compared to wild type strain. The results suggest that gacA(X00c) is
      involved chemotaxis of Xooc. Nevertheless, how gacA to regulate chemotaxis of
      Xooc, transcription and expression of genes involved in regulation still need to
      be further studied.

PMID- 17552222
TI  - [Construction and analysis of rumen bacterial artificial chromosome library from
      a dairy cow rumen microflora].
AB  - The high molecular weight DNA was extracted and purified directly from rumen
      samples in the study by using culture-independent and pulsed field gel
      electrophoresis approaches. After digestion with Hind III, DNA fragments ranging
      from 50-100 kb was collected and ligated to pCC BAC vector. The ligation mixture
      was transformed into E. coli EPI300 and a rumen metagenomic BAC library with
      about 15360 clones was constructed. The average insert size is about 54.5 kb,
      mostly ranging from 50-70 kb, and the capacity of this BAC library is about
      837Mb. Several BAC clones with activity of amylase, Cmcellulase had been screened
      from the BAC library. The clones with Cmcelluase activity were screened further
      for linchenase, xylanase, cellobioase activity and the result is that 25 of them
      have at least one kind of other enzyme activity.

PMID- 17552223
TI  - [Expression of mosquitocidal Cyt1Aa toxin from Bacillus thuringiensis subsp.
      israelensis in Asticcacaulis excentricus].
AB  - Asticcacaulis excentricus, who lives in upper-layer waters providing food
      resource to the mosquito larvae and has been proven to be a successful host to
      produce the mosquitocidal binary toxins or Cry11Aa toxin from Bacilli (Liu et
      al., 1996, Nat Biotech 14: 343; Armengol, et al. , 2005, Curr Microbiol 51: 430),
      was developed to express cyt1Aa gene from Bacillus thuringiensis subsp.
      israelensis (Bti). Two A. excentricus transformants were constructed with the
      attempt of producing CytlAa alone and alongside with Cry11Aa, repectively.
      Detection of expressed Cry11Aa and CytlAa proteins by immunoblot in the
      recombinant A. excentricus clones showed that either cry11Aa or cyt1Aa was
      expressed well solely but not simultaneously although both restriction analyses
      of plasmid DNA and DNA sequencing showed that the transformed plasmid was
      identical to scheme. To investigate the reason why the recombinant A. excentricus
      harboring both genes and their ribosome binding site (RBS) sequences expressed
      only Cry11Aa, the total RNA of A. excentricus cells was extracted and revealed
      three-band pattern in which all RNA molecule weights are not greater than 16S RNA
      of Escherichia coli by formamide agarose gel electrophoresis, indicating that
      different RNA systems within these two Gram-negative strains required
      distinguishingly organised constructs to express multiple foreign genes. It is
      hypothesized that an extra promoter upstream of RBS sequence is required to
      express cyt1Aa in the cry11Aa-cyt1Aa tandom plasmid.

PMID- 17552224
TI  - [Characterization of multidrug-resistant Salmonella serovars isolated from meats
      and human samples in some regions of Jiangsu].
AB  - A total of 117 Salmonella strains isolated from retail meats and human in some
      regions of Jiangsu were assayed for their antimicrobial susceptibility, the
      presence of integrons and antimicrobial resistance genes, and the ability of
      horizontal transfer of the characterized antimicrobial resistance determinants
      via conjugation. 111 (94.9%) were resistant to at least two antimicrobial agents.
      Resistance against streptomycin 92.3% (108/117) was the most common. Whereas 59
      (50.4%) were resistant to at least five antimicrobials. Twelve isolates showed
      resistance to six antimicrobials: ampicillin, chloramphenicol, streptomycin,
      sulfamethoxazole, tetracycline, and kanamycin (R type ACSSuTK). A total of 15
      different antimicrobial resistance genes were identified in 36 multidrug
      resistant Salmonella isolates. While 30 (83%) of these isolates tested carried
      integrons ranging in size from 0.3 to 1.6 kb. The most common integron was 1.6 kb
      which carried aadA5 and dfrl7 gene cassettes. Conjugation studies demonstrated
      that there was plasmid-mediated transfer of antimicrobial resistance genes. These
      data showed that the Salmonella isolates recovered from meats and human in some
      regions of Jiangsu were commonly resistant to multiple antimicrobials, and genes
      conferring antimicrobial resistance in Salmonella were often carried on integrons
      and plasmids and could be transmitted through conjugation. The mobile DNA
      elements might played very important role in transmission and dissemination of
      antimicrobial resistance determinants among Salmonella strains.

PMID- 17552225
TI  - [Screening and characterization of marine bacteria with antibacterial and
      cytotoxic activities, and existence of PKS I and NRPS genes in bioactive
      strains].
AB  - Antibacterial and cytotoxic activities were screened for marine bacteria which
      have been isolated from organism, sediments and seawater in China coastal area.
      The results showed that 42 isolates had antimicrobial activity and 12 isolates
      had cytotoxicity. Molecular phylogenetic analysis of marine bacteria with
      cytotoxicity based on 16S rRNA sequences indicated that they were belong to the
      genera Aerococcus, Agrobacterium, Alteromona, Bacillus, Exiguobacterium,
      Paracoccus, Pseudoalteromons, Rheinheimera. Furthermore, marine bacteria with
      cytotoxicity were also screened for PKS I and NRPS genes which could be
      responsible for bioactive secondary metabolites biosynthesis, 4 strains having KS
      domain or A domain were obtained, which provide strong evidence that marine
      bioactive bacteria can produce natural products through PKS and NRPS pathways.

PMID- 17552226
TI  - [Quantitative competitive RT-PCR and quantitative detection of Escheriia coli
      acrA-mRNA].
AB  - A Quantitative detection assay of acrA-mRNA of Escherichia coli ATCC25922 was
      developed by Quantitative Competitive RT-PCR. Target Standard(TS) which was same
      as target-templete acrA was amplified by PCR with P1 and P2 as primers. Internal
      Standard (IS) which was shorter 68 bp then target-templete acrA was amplified by
      temperature-gradient-PCR with P1 and P3P2 as primers, whose annealing
      temperatures ranged from 55-65 degrees C, and the most suitable annealing
      temperature was acquired at 56 degrees C. Both TS and IS were largely amplified
      by PCR as above and extracted to store. Co-amplification with both TS and IS as
      templetes was optimized by temperature-gradient-PCR with P1 and P2 as primers,
      whose annealing temperatures were ranged from 55-65 degrees C, and then the most
      suitable annealing temperature was also acquired at 56 degrees C. Then co
      amplification optimized as above was did again but with both cDNA of Escherichia
      coli (with target-templete acrA-cDNA copies unknown) and IS (10-fold serial
      dilution, and with IS copies known) as templates. The electrophoresis bands were
      photographed and analysed with UVI band and each band area was acquired, then
      linear regression analysis was did with SPSS ll.5 and CurveExpert l.3 and a
      competitive curve was drawn as y = -0.345 + 0.097x. Results revealed that the two
      kinds of product electrophoresis bands of co-amplification, whose templates were
      both 10-fold diluted IS and cDNA, could be distinguished clearly in 1.5% agarose
      gel because of 68bp discrepancy, and showed lighteness dimming gradually with IS
      copies 10-fold diluting. With the competitive curve, the copies of acrA-mRNA in
      sample could be counted accurately and easily.

PMID- 17552227
TI  - [Comparative study on identity of B. ovis 019 strain by traditional methods and
      HOOF-prints technique].
AB  - B. ovis 019 strain was identified by traditional methods and HOOF-Prints
      technique. Software DNAMAN was used to analyze phylogenetic tree for B. ovis 019
      and reference strains of B. abortus 2308, B. melitensis 16M, B. suis 1330 and B.
      ovis 63/290. The results showed that the similarity between B. ovis 019 and B.
      ovis 63/290 was higher than that between B. ovis 019 and the other reference
      strains, which was in accordance with the results by conventional bacteriological
      methods. HOOF-Prints technique would be a promising method for identifying
      Brucella species and even biovars.

PMID- 17552228
TI  - [Bioconversion of conjugated linoleic acid by resting cells of Lactobacillus
      plantarum ZS2058 in potassium phosphate buffer system].
AB  - Lactobacillus plantarum ZS2058, which was screened from the Chinese traditional
      fermented vegetable, has the capacity to convert the linoleic acid (LA) into
      conjugated linoleic acid (CLA). Some specific isomers of CLA with potentially
      beneficial physiological and anticarcinogenic effects, were efficiently produced
      from free linoleic acid by washed cells of Lactobacillus plantarum ZS2058 under
      aerobic conditions. The produced CLA isomers are identified as the mixture of cis
      9, trans-ll-octadecadienoic acid (CLA1) trans-10, cis-12-octadecadienoic acid
      (CLA2), 96.4% of which is CLA1. The washed cells of Lactobacillus plantarum
      ZS2058 producing high levels of c9, t11-CLA were obtained by cultivated in MRS
      media containing 0.5 mg/mL linoleic acid, indicating that the enzyme system for
      CLA production is induced by linoleic acid. After a 24-hour bioconversion at 37
      degrees C with shaking (120 r/min), 312.4 microg/mL c9, t11-CLA is produced. And
      after a 36-hour bioconversion, the content of c9, t11-CLA decreases while hydroxy
      octadecaenoic acid increases. In addition, the c9, t11-CLA isomer can be
      transformed to hydroxy- octadecaenoic acid when the mixed CLA (c9, t11-CLA and
      t10, c12-CLA) were used as the substrate, which suggests that c9, t11-CLA is one
      of the intermediates of the bioconversion products from free LA by washed cells
      of Lactobacillus plantarum ZS2058.

PMID- 17552229
TI  - [Pathway analysis for production of L-leucine by Brevibacterium flavum TK0303].
AB  - Brevibacterium flavum is used for the production of a number of amino acids in
      the biotechnology industry. The yield of producing a metabolite is ultimately
      limited by the ability of the central metabolism and the desired biosynthesis
      pathway. Pathway analysis is a very useful tool for metabolic engineering, which
      can be applied to increase the yield of a metabolite or channeling a metabolite
      into desired pathways. It does not require any kinetic parameters and only uses
      the Stoichiometric equations. Pathway analysis for production of L-leucine by
      Brevibacterium flavum TK0303 at steady state was conducted in this paper.
      Theoretical yield and flux distribution for optimal pathway were determined. It
      is also concluded that pyruvate and acetyl-coenzyme A are the key nodes of the L
      leucine biosynthesis pathway by analyzing the flux distributions of different
      modes. According to the pathway analysis, the production of L-leucine is expected
      to be raised by strengthening the flux of the key nodes (pyruvate and acetyl
      coenzyme A) through changing the environmental factors. Because the flux of TCA
      cycle in Brevibacterium flavum TK0303 is weak, the production of L-leucine must
      be provided enough amido by adding glutamic acid to the fermentation medium.
      NH4Ac is both a carbon source and a nitrogen source, which could be helpful to
      the production of L-leucine. The effects of glutamic acid and NH4Ac on the
      production of L-leucine were further studied. The production of L-leucine
      increased 56% by adding glutamic acid. By improving the concentration of NH4Ac,
      the biosynthesis of L-leucine was greatly strengthened too. The results indicate
      that the flux of L-leucine can be largely increased by changing the chemical
      regulatory factors such as NH4Ac and glutamic acid and the modes established by
      pathway analysis prove to be efficient to describe the metabolic network of L
      leucine production by Brevibacterium flavum TK0303.

PMID- 17552230
TI  - [Construction of Pseudomonas sp. M18 qscR- mutant and its regulation on
      biosynthesis of PCA and Plt].
AB  - In Gram-negative bacteria, global regulator QscR controls the expression of many
      virulence determinants, secondary metabolites, stationary phase genes and genes
      involved in biofilm formation through quorum sensing (QS) systems. QscR binds the
      promoter region of target genes and regulates the gene expression at the
      transcriptional level. Using homologous recombination technique a chromosomal
      qscR inactivated mutant strain M-18Q was constructed in Pseudomonas sp. M-18, a
      strain of plant-growth-promoting rhizobacteria, which could inhibit several
      soilborn phytopathogens by producing secondary metabolites including phenazine-1
      carboxylic acid (PCA) and pyoluteorin (Plt) in one single strain. To further
      study the effect of QscR on the synthesis of Plt and PCA in the wild type strain
      M-18, the dynamic curves of Plt and PCA produced respectively by M-18 and M-18Q
      strains were measured in both KMB and PPM mediums. The synthesis of PCA was much
      more activated in the mutant than in the wild type both in KMB and PPM mediums.
      The PCA production in the mutant strain is four-to-six fold over that in the wild
      type in the PPM medium, reaching 480 pg/mL, and three-to-five fold in the KMB
      medium, reaching 140 microg/mL. The synthesis of Plt, however, was not detected
      in PPM medium and was nearly not influenced by the QscR protein in KMB medium.
      PCA production was inhibited but Plt biosynthesis was not altered after
      complementation with qscR gene in trans in the strain of M-18Q. The regulation of
      qscR gene on PCA production was further confirmed by the analysis of beta
      galactosidase activities from the translational phzA '-' lacZ fusion, in which
      phzA is the first enzyme gene of the phenazine biosynthesis pathway. These
      results indicate that QscR can control PCA production negatively but not Plt
      production in M-18, and show that QscR functions as a global regulator to
      differently regulate the synthesis of PCA and Plt on the gene expression level.

PMID- 17552231
TI  - [Mode of action of plantaricin L-1, an antilisteria bacteriocin produced by
      Lactobacillus plantarum].
AB  - Plantaricin L-1, an anti-Listeria bacteriocin, was produced by Lactobacillus
      plantarum and successfully purified by SP-Sepharose FF cation exchange
      chromatography. The mechanism on energized cells of Listeria monocytogenes was
      studied with purified plantaricin L-1. After adding plantaricin L-1 to Listeria
      monocytogenes at 64 AU/mL, leakage of intercellular K+ ions, inorganic phosphate,
      lactic dehydrogenase, UV-absorbing materials and the intracellular ATP was
      observed, and the action resulted in the dissipation of the membrane potential
      (delta psi) and pH gradient (delta psi), two components of the proton motive
      force (PMF). All the data suggested that the primary site of action of
      plantaricin L-1 was the cytoplasmic membrane of sensitive cells. By forming the
      nonselective pores which leak ions and small organic compounds plantaricin L-1
      induced the cells death, this action was similar to membrane corruption caused by
      peptide effect. Penetrability increased due to the enlarged pore and dysfuction
      of membrane transporters, which ensured efficient killing of target bacteria.

PMID- 17552232
TI  - [Mutation spectrum analysis of transglutaminase gene in Streptomyces fradiae
      after irradiation by N+ ion].
AB  - A series of mutants of transglutaminase (TGase) gene from Streptomyces fradiae
      strains were obtained by low energy N+ ion beam irradiation, and the irradiation
      dose response curve was also investigated. Both the wild type and the mutants of
      TGase were compared by PCR-SSCP, and specific fragments were sequenced. Then the
      types of TGase gene mutation induced by N+ were characterized. The results show
      that the types of DNA base mutation included the transition, the transversion and
      the deletion. In all of the 24 bases of mutants, the base replacement occupies
      about 87.5% of the total mutants with only a small portion of gene deletion
      (12.5%). Interestingly, the frequency of the base transition (58.3%) is obviously
      higher than that of the base transversion (29.2%) among the base replacements.
      The base substitutions induced by N+ ion beam irradiation are C-->T transition, A
      ->G transition, G-->T transversion, C-->G transversion. Furthermore, mutations
      can be induced in all of the four DNA bases by low energy N+ ion beam
      irradiation, and cytosine shows the highest frequency of mutation.

PMID- 17552233
TI  - [Stringent RNA polymerase of E. coli and its in vivo transcriptional activity].
AB  - Several spontaneous E. coli mutants with the similar phenotype as that in the
      condition of amino acid deficiency were obtained on the selective media. One of
      the mutants (LCH001) showing slow growth phenotype on LB agar plate and pink or
      white colonies on MacConkey agar plate was mapped at rpoC gene encoding the beta'
      subunit of RNA polymerase by phage P1 transduction and transformation assays and
      found to be a new site mutation from G to T at 3406bp in the rpoC gene, which
      resulted in the amino acid change from Glycine (GGT) to Cysteine (TGT). The
      effect of the mutation on transcriptional activity of both stringent and non
      stringent controlled promoters in vivo was measured by determining the beta
      galactolactase activity of the growing cells. Results showed that the
      transcriptional activity of the mutant LCH001 reduced greatly on the stringent
      promoter, but increased significantly on the non-stringent promoter. The beta
      galactolactase activity of the mutant LCH001 transcribed on stringent promoter
      was 18% lower, but 5-fold higher on the non-stringent controlled promoter than
      that of the wild-type strain CLT5034. This finding may give insights into future
      studies of the structure-function relationship of RNA polymerase as well as its
      role in the stringent response of bacteria.

PMID- 17552234
TI  - [Effect of over-expression of sterol C-22 desaturase on ergosterol production in
      yeast strains].
AB  - Ergosterol, the main sterol in yeast, is responsible for structural membrane
      features such as fluidity and permeability. Additionally, ergosterol is
      economically important as a precursor of vitamin D2. The biosynthesis of sterols
      in yeast is complex. As an enzyme of the later ergosterol biosynthesis, the
      sterol C-22 desaturase encoded by ERG5 gene is required to form the C-22 (23)
      double bond in the sterol side chain. In order to know the regulation of C-22
      sterol desaturase in the ergosterol biosynthesis, ERG5 gene was cloned and over
      expressed in the Saccharomyces cerevisiae. Primer 1 (5'
      GTCGGTACCTCCAATGACAATAAATACC-3', Kpn I) and primer 2 (5'
      AAGGATCCTAGCAGATCATTAGCTGTAG-3', BamH I) were designed according to the ERG5
      sequence in GenBank. A 1.8 kb DNA fragment containing the open reading frame and
      terminator of ERG5 gene was amplified from Saccharomyces cerevisiae YSF-20 by PCR
      and inserted into YEp352 to generate recombinant plasmid pYE5. To express ERG5
      gene properly in S. cerevisiae, the recombinant expression plasmid pYPE5
      containing ERG5 from pYE5 under the control of PGK1 promoter, the URA3 gene as
      the selection marker and the plasmid YEp352 as the vector was constructed, and
      then they were introduced into Saccharomyces cerevisiae YS58. To make sure the
      plasmid pYPE5 in the YS58 acted properly, the disruptant (YSE5) was created by
      deleting a 0.4 kb fragment of ERG5 gene and inserting the CUP1 gene into the ERG5
      and transforming the YS58. And then the disruptant (YSE5) was transformed with
      the plasmid pYPE5 carrying the corresponding complementing ERG5 gene to control
      the activity of the over-expressed ERG5 gene and restauration of the wild-type
      sterol pattern. The sterol profile of the disruptant (YSE5) demonstrated that
      ergosta-5, 7-dien-3beta-ol was accumulated which was very similar to ergosterol
      but with a saturated side chain. In contrast, the YSE5 (pYPE5) strain contains
      predominantly ergosterol. The sterol content of the transformant was analyzed
      using gas chromatography (GC) analysis. The result shows that ergosterol
      production in recombinant strains was reduced. And the experiment of the effect
      of culturing time shows that ergosterol productions in recombinant strains were
      always lower than YS58 (pYPE5) from 24-48 h culturing time. Under the optimal
      culture condition, ergosterol content in recombinant strain YS58 (pYPE5) was
      about 0.70-fold of that in the referring strain.

PMID- 17552235
TI  - [Construction of a double functional recombinant strain of Pichia pastoris co
      expressing phytase and mannanase and the enzymatic analyses].
AB  - Co-expression of phytase and mannanase in Pichia pastoris is a useful way to
      reduce the production cost in feedstuff industry. Based on the published DNA
      sequences of phytase gene and mannanase gene, primers were designed and genes
      phyA and man were cloned by PCR from Aspergillus terreus and the plasmid
      pHBM1201, respectively. Then the two fragments were treated and inserted into the
      same expression vector pHBM907C, which contains both the methanol-inducible
      promoter and the transcription terminator of the AOX1 gene, resulting the plasmid
      pHBM907C-phyA and the plasmid pHBM907C-man. The phyA expression cassette was
      combined to the expression vector pHBM907C-man which contains the expression
      cassette of mannanase, so pHBM907C-phyA-man was obtained. The recombinant
      expression plasmid pHBM907C-phyA-man was digested by Sal I and introduced into
      the chromosomes of Pichia pastoris GS115 by using the LiCl/PEG method. Following
      transformation, several parameters that demonstrated the expression of phytase
      and mannanase were measured. Firstly, the two different Petri dishes that contain
      enzymatic substrates such as calcium phytate and mannose were screened
      simultaneously, thus 100 clones were found to be positive on both of these
      plates. Secondly, 6 clones among them were chosen for induced expression at
      shakeflasks showing the probability of high expression. After that, some relative
      enzymatic properties were measured. At 72 hours' induction in the condition of
      shake cultivation, the enzyme activity of phytase in supernatant was 120.6 U/mL,
      while the enzyme activity of mannanase in supernatant was 39.7 U/mL. The
      expression product phytase was active under pH 2.0-6.5, and the activity was up
      to the highest under pH 5.5. And the other expression product mannanase was
      active under pH 5.5-10.5, and the activity was up to the highest under pH 7.5.
      The optimal temperatures for the two enzyme were both around 52 degrees C: the
      optimal temperature for phytase activity was 50 degrees C, and that for mannanase
      was 55 degrees C. At last, stability test of the engineered yeast was taken, and
      the engineered yeast still showed an excellent stability even after 10 generation
      growth in the absence of selective pressure. The stable double functional
      engineered yeast simultaneously expressing extracellular phytase and mannanase is
      obtained. It will satisfy the demand for industrialized production in some
      degree.

PMID- 17552236
TI  - [Use of rpoB and 16S rDNA genes to analyze rumen bacterial diversity of goat
      using PCR and DGGE].
AB  - DNA extraction from the rumen of three species of goat (boer goat, Nanjiang
      yellow goat, Inner Mongolia cashmere goat) was followed by Polymerase Chain
      Reaction (PCR) amplification of the beta subunit of the RNA polymerase (rpoB) and
      16S rDNA genes. PCR products were compared by Denaturing Gradient Gel
      Electrophoresis (DGGE) to compare the predominant bacterial community structure.
      The results showed the rpoB DGGE profiles comprised fewer bands than those of 16S
      rDNA profiles and were easier to analyze. The gene for rpo B is a single copy
      gene unlike 16S rDNA. So using the rpoB gene offeres a better alternative to the
      commonly used 16S rRNA gene for microbial community analyses based on DGGE. The
      bacteria community structure of different goats were similar to each other. The
      similarities within species were noticeably higher than that between species.
      Goat species were found to influence the rumen microbe community. Phylogenetic
      and sequence similarity analyses of the resultant 14 clone sequences in16S rDNA
      DGGE libraries revealed that 4 clone show similarity over 97% with that of
      database sequences, while the rest present similarity in a range of 89%-96%, and
      13 clone of all were similar to those unidentified rumen bacteria. These results
      suggest that DGGE followed by clone technique is a practicable protocol to
      research the complex community of rumen microbe.

PMID- 17552237
TI  - [Microbial diversity in shengli petroleum reservoirs analyzed by T-RFLP].
AB  - Recent investigations on the microbial ecology of oil reservoirs in a variety of
      locales indicated that these habitats harbor various assemblages. In this study,
      a cultured-independent molecular technique, Terminal Restriction Fragment Length
      Polymorphism (T-RFLP), was used to analyze the microbial diversity of an
      injection well (S12-ZHU) and three related production wells (S12-4, S12-5 and S12
      19) in the ShengLi oilfield (Shandong province, China). The 16S rRNA genes were
      amplified by PCR with the 5'carboxy-fluorescein (5-FAM)-labelled universal
      forward primers (27F for bacteria and 21F for archaea) and a universal reverse
      primer (1495R). Then the 16S rRNA genes were digested with restriction enzymes
      (Hae III and Hha I) and analyzed by using an automated DNA sequencer. The Shannon
      Wiener Diversity index, based on the T-RFLP profiles, indicated that the
      bacterial and archaeal species richness in the injection well was higher than
      those of the production ones. The similarity coefficient showed the microbial
      community similarity among the four samples was 22.4%-30.8% (Bacteria) and 20.8%
      34.5% (Archaea), respectively. According to the analysis by TAP T-RFLP program,
      species belonging to Pseudomonas, Marinobacter and Methanosarcina as well as some
      uncultured archaeon were supposed to be the dominant bacteria in all four
      samples. Thus, this study indicates that T-RFLP is useful for analysis of the
      microbial diversity in petroleum reservoirs.

PMID- 17552238
TI  - [Prokaryotic microbial diversity of the ancient salt deposits in the Kunming Salt
      Mine, P.R. China].
AB  - The prokaryotic microbial diversity of the ancient salt deposits in the Kunming
      Salt Mine, PR China was investigated using PCR-DGGE and rRNA approaches. Total
      community DNA was extracted and purified by a direct method, which yielded
      amplified DNA of high molecular weight for samples. A variable region of 16S rRNA
      gene was then amplified by PCR with bacterial and archaeal primers and analyzed
      by denaturing gradient gel electrophoresis (DGGE). Twenty-seven major bands were
      detected in the bacterial DGGE profile of the sample, but only one band of pure
      culture strains of bacteria isolated from the Kunming Salt Mine matched with one
      band of sample. No band of pure culture strains of archaea isolated from the
      Kunming Salt Mine matched with 18 major bands of sample. The results indicated
      that most of microbes in this environment are likely uncultivable. Clones on the
      plate were not the predominant species in the community. Two 16S rRNA gene clone
      libraries (bacteria and archaea) were also constructed, and 36 and 20 clones were
      selected for amplified ribosomal DNA restriction analysis (ARDRA). ARDRA with
      enzymes Afa I, Hha I, Hae III revealed 10 bacterial operational taxonomic units
      (OTUs), with three most abundant OTUs accounting for 38.9%, 25.0%, 16.7% of all
      the bacterial 16S rDNA clones, respectively. The remaining 7 OTUs presented at
      low levels, were represented by a single clone. Eight archaeal OTUs were obtained
      but no predominant OTUs. Some clones were sequenced and each sequence was
      compared with all nucleotide sequences in GenBank database. Examination of 16S
      rDNA clones showed that the ancient salt deposits in the Kunming Salt Mine
      contained a phylogenetically diverse population of organisms from the Bacteria
      domain with members of three major lineages represented: alpha-proteobacteria,
      gamma-Proteobacteria and Actinobacteria, especially Pseudomonas. Surprisingly, we
      recovered a variety of sequence closely related to Actinobacteria which was not
      found in other salt deposits. All of archaeal clones are from Halorubrum,
      Haloterrigena and uncultured archaea. The results of DGGE and clone library
      profiling analysis both indicated that microbial community of the Kunming Salt
      Mine had higher diversity. In this initial survey, our polyphasic approaches
      demonstrated that novel and uncultured microbes thrive in the ancient salt
      deposits of the Kunming Salt Mine. Molecular analysis of the microbial diversity
      in salt deposits provides foundation for better application of microbial
      resources.

PMID- 17552239
TI  - [Comparison of nitrifying populations between a lab-scale system and an
      industrial system treating coking wastewater].
AB  - Molecular analysis of community structure can help diagnose problems in
      malfunctioning full-scale wastewater treatment system. A lab-scale A1-A2-O fixed
      biofilm system with highly efficient nitrification (NH3-N removal at 95. 2%) was
      set up as a reference for an industrial system with poor performance of
      nitrification (NH3-N removal efficiency at -106%) for treating coking wastewater.
      Composition of nitrifying bacteria of biofilm samples in aerobic reactors of the
      two systems was compared by 16S rDNA clone library analysis. The composition of
      clone library of the lab-scale system indicate Nitrosomonas europaea-Nitrosoccus
      mobilis cluster and sublineage I of Nitrospira genus are dominant ammonia and
      nitrite oxidizers in this process respectively. However, there were no clones
      related to nitrifying bacteria in clone library of the industrial system which
      suggested low abundance of nitrifying bacteria in this system. Further, Real-Time
      PCR with Taqman probe revealed that 16S rDNA copy number of Nitrospira in aerobic
      reactor of the lab-scale system was 3.4 x 10(6)/microg DNA of biofilm which is
      300 times higher than that in the industrial system. The absence of Nitrosomonas
      and Nitrospira in the industrial system leads to poor performance of
      nitrification. Building up of a high population level of Nitrosomonas and
      Nitrospira in aerobic reactor is the key to improve efficiency of nitrification
      of the industrial system.

PMID- 17552240
TI  - [Function analysis of the effective strain Rhodococcus ruber Em1 in wastewater
      treatment system by quantitative competitive PCR].
AB  - A quantitative competitive PCR (QC-PCR) system was developed to quantify the
      number and analyze the function of the Rhodococcus ruber Em1 strain in a
      wastewater treatment system in Nanchong oil refinery plant. Strain Em1 was able
      to degrade various kinds of hydrocarbons and aromatic compounds with high
      efficiency and produce bioemulsifier, so it was introduced into the waste liquid
      petroleum-disposing system. The sediment samples were collected from the
      disposing system in the range of 5 months, and then the numbers of strain Eml and
      degrading efficiencies were studied. The results showed that the primers based on
      16S rRNA gene sequence of strain Em1 were specific at species level. The PCR
      products amplified from sediment total DNA with the specific primers were cloned
      and sequenced, in which 62.2% were the fragments of 16S rRNA gene of strain Em1.
      Furthermore, the number of Em1 strain ranging from 3.4 x 10(5) - 4.3 x 10(8)
      CFU/g in the sediment samples were detected, which indicated that the strain Eml
      added into purposely did exist stably and reproduced well in the waste-deposing
      system during a long period. The high relativity, with relative coefficient R2 of
      0.89, between Eml cell number and the amount of COD (Chemical Oxygen Demand)
      removal proved that the strain Em1 played an important role in this bio
      augmentation treatment system.

PMID- 17552241
TI  - [Influence of organic pollutants on the bacterial community in Songhua River
      drainage area].
AB  - In order to investigate the potential influence of the organic pollutants on the
      microbial composition and diversity, terminal restriction fragment length
      polymorphism (tRFLP) and 16S ribosomal DNA (rDNA) clone libraries combined with
      water quality analysis were selected to compare the structure of bacterial
      communities in four water bodies contaminated by different degrees of organic
      matter. tRFLP profiles of the waters and sediments all showed complex patterns
      and high similarity, however, some certain populations enriched with the
      pollution enhanced. Especially, the similarity of communities accorded strictly
      with that of water quality. Principal component analysis (PCA) indicated that the
      terminal restriction fragments (TRF) of bacteria in the waters and sediments
      grouped into different clusters. 16S ribosomal DNA sequences in the Songhua River
      sediment fell into ten known phyla and Proteobacteria are predominant with 21.92%
      of clones (in which the beta-Proteobacteria accounts for 10.96%). The sediment
      seriously polluted by domestic wastewater comprised of only 7 phyla, in which
      Proteobacteria was predominant with 47.37% of clones (subdivisions a
      Proteobacteria and delta/epsilon-Proteobacteria were 21.05% and 15.79%,
      respectively). This study demonstrated that the long-term drainage of organic
      wastewater reduced the microbial diversity, and some functional microbes that are
      responsible for the degradation of organic matter, became dominant.

PMID- 17552242
TI  - [Display of the F18 fimbrial adhesin on the bacterial surface using type V
      secretion system and characterization of the binding domain of the adhesin].
AB  - The beta domains of autotransporters (also called type V secretion system) have
      been demonstrated to be feasible tools to display foreign passenger domain on the
      bacterial surface. In the present work, using the DNA manipulation the type V
      secretion system MisL displaying the binding doamin FedF1 of the F18ab fimbrial
      adhesion was constructed, and the full length adhesin FedF of F18ab fimbriae and
      the FedF mutant (with the 88th and 89th amino acid residues changed from
      Histadine to Alamine) on the surface of E. coli DH5alpha, respectively. The
      recombinant E. coli DH5alpha with the different recombinant plasmids of pnirBMisL
      fedF1, pnirBMisL-fedF and pnirBMisL-fedF(M) were induced at anaerobic conditions.
      After induction, the binding doamin FedF1 of the FedF and adhesin FedF displayed
      on the surface of E. coli DH5alpha were tested for their agglutination and
      adhesion capability with the anti-rabbit sera against FedF subunit or the small
      intestinal epithelial cells from susceptible piglets. The results showed that the
      pnirBMisL-fedF1 or pnirBMisL-fedF recombinant bacteria could agglutinate with the
      anti-rabbit sera against FedF subunit and adhere to the small intestinal
      epithelial cells well. But the recombinant bacterial strain with the recombinant
      plasmid pnirBMisL-fedF(M) completely abolished the agglutination characteristic
      and receptor adhesiveness. These results confirmed that the binding doamin FedF1
      of the F18ab fimbrial adhesin and the adhesin FedF of F18ab fimbriae could be
      transported and displayed functionally on the surface of E. coli DH5alpha by
      using type V secretion system and the His-88 and His-89 amino acid residues
      located in the FedF adhesin were important for the formation of the binding
      domain of the adhesin FedF of Fl8ab fimbriae.

PMID- 17552243
TI  - [Construction of recombinant BCG bearing S1 glycoprotein of nephropathogenic IBV
      and study on its immunogenicity on chickens].
AB  - Glycoprotein Si was the major protein to determine infection and immunogenicity
      of Infectious bronchitis virus (IBV). The S1 glycoprotein gene of IBV isolates
      were amplified by reverse transcriptase-polymerase chain reaction (RT-PCR) and
      proved to be S1 gene by sequencing. The E. coli-mycobacterium expression shuttle
      plasmid pR-alpha-S1 was constructed by inserting the S1 gene to the pRR3 with
      human mycobacterium tuberculosis HSP70 promoter and a signal peptide. Then the
      plasmid pR-alpha-S1 was introduced into mycobacterium bovis BCG by
      electroporation to construct a recombinate strain rBCG-Sl. The S1 protein could
      be highly expressed in M. smegmatis mc2 155 when induced by heating and was
      detected by ELISA and Western blot assays using monoclonal antibody against S1
      glycoprotein of IBV. 6 week-old SPF chicken were subcutaneously immunized with
      10(6) cfu rBCG-S1 and each chick was immunized three times at 3 week intervals
      with the same antigen used for the primary immunization. The protective immunity
      of rBCG-S1 was identified in vaccinated chickens. Results from the protection
      test showed the two immunizations with rBCG-S1 could provide protection for
      chickens from the challenge with virulent nephropathogenic IBV strain X.
      Haemagglutination inhibition titers were also increased in chickens immunized
      with the expressed rBCG-S1, and significantly higher titers were detected after
      challenge. These data indicate that the rBCG-S1 could be used as candidate of a
      live vector vaccine for NIBV.

PMID- 17552244
TI  - [Membrane location and naturally antibody responses of genus-specific antigen
      OmpL1s of Leptospira interrogans].
AB  - The major aim of this study is to determine the location on outer envelope of the
      genus-specific antigen OmpL1s of Leptospira interrogans, and the inducement of
      naturally antibody response and types of the antigen, which will offer the
      evidences to use OmpL1s as the antigen candidate for developing universal genetic
      engineering vaccine and detection kit. The serum samples from 156 leptospirosis
      patients in Sichuan area were detected using microscope agglutination test (MAT).
      By using PCR plus nucleotide sequence analysis, the genotypes of the dominant L.
      interrogans serogroups in China were demonstrated. Routine genetic engineering
      technique was applied to construct the prokaryotic expression systems of
      genotypes ompL1/1 and ompL1/2, and Ni-NTA affinity chromatography was performed
      to extract the target recombinant products rOmpL1/1 and rOmpL1/2. Immune aurosol
      electron microscopy was selected to locate the position of OmpL1s on leptospiral
      envelope. ELISAs based on rOmpL1s were established to confirm the level and types
      of specific antibody. The results indicated that L. interrogans serogroup
      Icterohaemorrhagiae remains to be the most important dominant leptospiral
      serogroup in Sichuan area. There are two ompL1 genotypes of ompL1/1 and ompL1/2
      in the dominant leptospiral serogroup in China. And remarkable differences of the
      nucleotide and putative amino acid sequence similarities between the two
      genotypes are present. OmpL1s are the protein molecular that located on the
      external surface of leptospiral envelope. In the 156 cases of leptospirosis
      patients' serum samples using different dilutions, the positive rates for
      rOmpL1/1 or rOmpL1/2 specific IgM are 67.9%-79.5% and 75.0%-75.6%, while for for
      rOmpL1/1 or rOmpL1/2 specific IgG are 71.8%-79.5% and 75.0%-76.9%, respectively.
      All the results mentioned above lead to the conclusions that OmpL1s is the
      leptospiral genus-specific superficial protein antigen of L. interrogans and both
      rOmpL1/1 and rOmpL1/2 can induce humoral response in individuals naturally
      infected with L. interrogans as well as produce two serum antibodies IgM and IgG
      with extensive antigenic-cross reaction. Therefore, rOmpL1/1 and rOmpL1/2 can be
      used as the antigen candidate for developing universal genetic engineering
      vaccine and detection kit.

PMID- 17552245
TI  - [Construction and identification of recombinant canine adenovirus type 2
      expressing exogenous rabies glycoprotein (Rgp)].
AB  - Safe and effective vaccination is important for rabies prevention. Here,
      genetically engineered rabies vaccine CAV2-deltaE3-Rgp was developed and
      characterized. The recombinant genome pPoly2-CAV2-deltaE3-Rgp carrying the rabies
      glycoprotein (Rgp) cDNA was generated by a series of strictly gene cloning steps
      and infectious recombinant virus CAV2-deltaE3-Rgp was obtained by transfecting
      the recombinant genome into a canine kidney cell line, MDCK. To efficiently
      construct cloned recombinant canine adenovirus type 2 genome pPoly2-CAV2-deltaE3
      Rgp bearing exogenous Rgp gene, The Rgp gene was first subcloned from the clone
      vector pMD18-T into the eukaryon expression vector pVAX1. The Rgp expression
      cassette was then subcloned into the shuttle vector pVAXdeltaE3 and subsequently
      into the canine adenovirus type 2 backbone vector pPoly2-CAV2. To indirectly
      confirm pPoly2-CAV2-deltaE3-Rgp, conventional restriction endonuclease digestion
      was performed. CAV2-deltaE3-Rgp can generate typical CPE of CAV-2. CAV2-deltaE3
      Rgp was tested by restriction endonuclease digestion, PCR, DNA sequencing. As a
      result, The Rgp expression cassette was successfully integrated into the target
      region of the CAV2 genome. It is confirmed by RT-PCR, Western blot that CAV2
      deltaE3-Rgp can express Rgp antigen in MDCK cell. This recombinant virus, CAV2
      deltaE3-Rgp, was intramuscularly injected into dogs. All vaccinated dogs produced
      effective antibodies against CAV and RV after three inoculations. This
      recombinant virus would be prospective in immunizing dogs against CAV and RV.

PMID- 17552246
TI  - [Construction of recombinant Lactococcus lactis expressing porcine transmissible
      gastroenteritis spike glycoprotein and analysis of immunogenicity].
AB  - Transmissible gastroenteritis virus (TGEV), is an enteropathogenic coronavirus
      that causes a highly fatal acute diarrhea in newborn pigs. It's typically
      clinical manifestations consist of omitting, severe diarrhea, loss water and
      highly infectious disease. All kinds and ages of pigs can be infected.
      Particular, the mortality piglets under 3 weeks may reach 100% . The effective
      protection against TGEV requires the development of vaccines that are able to
      induce local mucosal immunization. Lactococcus lactis was selected as a bacterial
      carrier for the expression of TGEV spike glycoprotein. The gene of S glycoprotein
      was cloned into the Lactococcus lactis vectors pNZ8112. An approximately 2000 bps
      fragments of TGEV gene S that encompasses all the four major antigenic domains
      critical for neutralization was transformed into Lactococcus lactis NZ9000 by
      electroporation, resulting in the recombinant strain pNZ8112-Sa/NZ9000. The
      recombinant glycoprotein S was detected by SDS-PAGE and Western blot after
      induced by 1ng/mL nisin. The result indicated that the expressed product maintain
      the antigenicity of TGEV as expected. In order to detect the location of
      expressed protein, the yellow and green fluorescence of the recombinant strain
      pNZ8112-Sa/NZ9000 was detected by the IFA experiments, which indicated that the
      expressed recombinant protein was secreted and located on the surface of the
      bacterium cell. Oral immunization of BALB/c mice with recombinant strain that
      constitutively express the 66kDa fragment of the glycoprotein S, Specific anti
      TGEV glycoprotein S secret immunoglobulin A (sIgA) antibodies were detected by
      indirect enzyme linked immunosorbent assay (ELISA) in the feces after
      immunization. It was showed that the mice immunized with pNZ8112-Sa/NZ9000
      recombinant strain had produced clear antibody level anti TGEV, and which had
      provided important substance foundation and explored the feasibility of
      Lactobacillus as oral vaccine.

PMID- 17552247
TI  - [Construction and the immunogenicity of the recombinant Modified Vaccinia Virus
      Ankala co-expressing ORF4, ORF5 and ORF6 genes of porcine reproductive and
      Respiratory Syndrome Virus NJ-a strain].
AB  - To develop investigate the recombinant MVA(rMVA) vaccines against PRRSV
      infection, the ORF4, ORF5 and ORF6 of PRRSV NJ-a strain were subcloned into the
      MVA transfer vector p II LR and the resultant recombinant vector was called p II
      LR-ORF4/ORF5/ORF6. The rMVA was generated by transfecting MVA-infected BHK-21
      cells with the recombinant vector and screened by plaque purification after X-gal
      staining. After six rounds of purification, insertion of PRRSV GP4, GP5 and M
      genes into the MVA genome was confirmed by PCR analysis and expression of the
      three proteins was identified by Western-blot and IFA. Each of the tested mice
      was inoculated with 5 x 10(5) TCID(50)/mouse of the rMVA-GP4/GP5/M and boosted 3
      weeks later. Neutralization assay showed that PRRSV-specific neutralizing
      antibodies were detectable at 3 weeks and reached the highest titer (2(5)) by 8
      weeks after the primary vaccination, which maintained stable until the end of the
      experiment. The significant lymphocyte proliferation responses were also observed
      in mice immunized with rMVA-GP4/GP5/M. These results indicate the rMVA co
      expressing PRRSV ORF4, ORF5 andORF6 genes may be an attractive candidate vaccine
      for preventing PRRSV infection.

PMID- 17552248
TI  - [Isolation and characterization of Acidiphilium strain teng-A and its metabolism
      of fe (III) during pure- and mixed cultivation].
AB  - An acidophilic, aerobic and chemoheterotrophic bacterial strain Teng-A was
      isolated from acidic environmental samples collected at sulfidic hot springs of
      Tengchong County, Yunnan Province, China. Cells of strain Teng-A was rod-shaped
      (0.6-0.8 microm x 1.0 - 1.5 microm), Gram-negative, motile with flagella. Strain
      Teng-A grew well at temperature of 29-33 degrees C and at pH of 3.0-4.0. It used
      a wide variety of organic compounds for growth, but did not use ferrous iron,
      elemental sulfur, thiosulfate and tetrathionate as the sole energy source. Its G
      + C content was determined to be 69.6 mol%. Phylogenetic analysis based on 16S
      rRNA gene sequence demonstrated that it was closely related to species of
      Acidiphilium. Under anoxic conditions, the strain Teng-A reduced Fe(III) to
      Fe(II) with glucose or hy drogen as electron donor (reduction rate is 11.56 mg/L
      day and 15.34 mg/L x day, respectively). Metabolisms/Oxidation of ferrous iron by
      Acidithiobacillus ferrooxidans LJ-1 and Leptospirilum ferriphilum LJ-2, in the
      presence and absence of strain Teng-A were studied. When incubated with strain
      Teng-A, the oxidation rates of Fe(II) was slightly decreased at the first 3 days
      (0.44 g/L x day and 0.4 g/L x day respectively) compared to pure culture of At
      ferrooxidans and L. ferriphilum, but all Fe(II) was completely oxidized after 5
      days. It was found that the morphologies of precipitates of Fe (III) produced
      during pure and mixed cultivation were different. The potential application of
      Acidiphilium in bioleaching and its potential role during formation of
      precipitated ores were discussed.

PMID- 17552249
TI  - [Isolation and identification of Rhodosporidium toruloides R1 degrading N-acyl
      homoserine lactone].
AB  - In the present study, a AHL-utilizing strain RI was isolated and identified as
      the genus Rhodosporidium toruloides R1 by physi-biochemical approaches and 18S
      rDNA sequence analysis, and this strain was designated as R. toruloides R1.
      Results showed that R. toruloides R1 exhibited the ability to utilize and degrade
      the all N-acyl homoserine lactones tested in this study. Coculture of R.
      toruloides R1 with Erwinia carotovora subsp. Carotovora effectively inhibit the
      soft rot disease of patato caused by E. carotovora. To the best of our knowledge,
      this is the first report on AHL-degradation of yeast cells.

PMID- 17552250
TI  - [The phylogenetic analysis of 15 Geotrichum strains based on 26S rRNA gene D1/D2
      region sequencing].
AB  - The 26S rRNA gene D1/D2 domain sequences of 15 strains originally identified as
      Galactomyces geotrichum from the Chinese Industry Culture Collection (CICC) were
      determined. The results indicated that these strains differed from the type
      strain of Galactomyces geotrichum and other species of the genus remarkably. Two
      groups were recognized from the 15 strains which possibly represent 2 novel
      species of Galactomyces. Further molecular study is needed to confirm their
      taxonomic status.

PMID- 17552251
TI  - [Characterization of the ectC gene and its expression product in Halomonas sp.
      Nj223 from Antarctica deep-sea sediment].
AB  - A moderately halophilic bacterium Halomonas sp. NJ223 was isolated from
      Antarctica deep-sea sediment. This bacterium accumulates ectoine as the main
      compatible solute in response to severe osmotic stress. Ecoine synthase catalyzes
      circulation of gamma-N-acetyl-alpha, gamma-diaminobutyric acid (ADABA) to ectoine
      in the last step of the three enzymatic steps. The gene of ectoine synthase from
      this strain was amplified by PCR and the DNA sequence of a 393-bp segment was
      sequenced. The amino acid sequences of this enzyme present high homology to the
      known sequence. The significance of this gene was proved by the expression in
      Escherichia coli. Thus, the amplified fragment was cloned into the expression
      vector pET-his. The insert position, the size and the reading frame were
      identified by PCR, restriction digestion and the sequence analysis of the
      recombinant plasmids. SDS-PAGE shows that the relative molecular mass of the
      expression product was 15 kDa as predicted, which indicated that the recombinant
      plasmids could express the gene of ectoine synthase. The biosynthetic pathway of
      ectoine was partially elucidated by renaturation and enzyme activity detection of
      purified ectoine synthase in vitro. Determination of effect of pH and temperature
      on enzyme activity shows that the optimal reaction condition of pH was 8.0 and
      temperature was 25 degrees C.

PMID- 17552252
TI  - [The response to environmental pH of RIM101 pathway in Candida albicans].
AB  - Abstract: Candida albicans is the most common kind of human opportunistic
      pathogen and gets many attentions in recent years. A lot of research has been
      done. The sites this organism colonizes differ in pH. C. albicans must be able to
      response to the environmental changes for its survival and pathogenicity.
      Extracellular environment, especially pH changes,is critical for C. albicans
      morphological differentiation and virulence. RIM101 pathway is a conserved fungal
      signal transduction pathway and at least partly controls the cellular pH response
      through the activity of the zinc finger transcription factor Rim101p. This review
      concisely summarized recent research on RIM101 pathway, pH response and their
      relationship in C. albicans.

PMID- 17552253
TI  - [Research progress of ERIC (IRU)].
AB  - Repeat sequence exists in almost all organism genomes. Enterobacterial Repetitive
      Intergenic Consensus (ERIC), also named Intergenic Repetitive Unit (IRU), is a
      kind of intergenic repetitive sequence that exists predominantly in
      Enterobacteria. ERIC (IRU) was firstly discovered in Escherichia coli, followed
      by identification in many other bacteria. ERIC (IRU) is 127 bp long, and some
      with inserted sequences. Most ERIC (IRU) can be transcribed, and mRNA forms a
      stem-loop structure. ERIC (IRU) is restricted to transcribed regions of the
      genome, either in intergenic regions of polycistronic operons or in untranslated
      regions upstream or downstream of open reading framesn (ORF). ERIC (IRU) probably
      modulates the expression of flanking genes. ERIC (IRU) is highly conserved, for
      either its variation is restricted by the natural selection pressure, or it's
      "selfish DNA". ERIC-PCR described by Versalovic et al. can efficiently analyze
      the variation of different ecological systems and monitor the development of
      microbial flora of the same ecological system. In recent years, this technology
      has been applied to study the microbial population of animal intestinal tract.

PMID- 17552254
TI  - [Modern nutrition and development of new allergies].
AB  - The prevalence of food allergy varies between 1 and 8% and depends on age,
      countries, symptoms and allergens. Main food allergens remain peanut, nuts, egg,
      cow milk, wheat, soybeans and fish. However, novel food industrial processes have
      induced new food allergies. Some are related to unusual components, like lupine
      seeds or flour or to modified food, like wheat or soybean isolates. Other
      unexpected allergies are due to residues of strong allergens--like peanut or egg-
      which are present in very small amounts in processed food. Swiss and european
      legislation have edicted lists of allergenic foods which have to be specified to
      the consumers. However, the legislation remains still incomplete and labelling of
      novel food components or modified allergens as well as as trace allergens is
      still far from being exhautive.

PMID- 17552255
TI  - [Atopic dermatitis and food allergies].
AB  - Around 13% of children in Switzerland are affected by atopic dermatitis.
      Cutaneous defects with increased water loss and allergens permeability are
      hallmark of the disease. The prevalence of food allergy in children with moderate
      to-severe atopic dermatitis is estimated to be 34%, mostly to eggs, milk and
      peanuts. Food allergy can cause immediate reactions with urticaria and
      anaphylaxis or delayed flares of eczema. In older patients and adults, exposition
      to respiratory allergens (dust mites, pollen) can also cause an exacerbation of
      the eczema. Allergy testing identifies patients with atopy, who are at greater
      risk of rhinitis and asthma. Skin prick tests, in vitro tests and food challenges
      can identify a concomitant allergy, leading to specific allergen avoidance mea
      sures potentially improving skin symptoms.

PMID- 17552256
TI  - [Treatment of asthma and rhinitis during pregnancy and breast feeding].
AB  - Inhaled therapies are preferred to systemic ones during pregnancy and breast
      feeding. A real paradox exists however between the necessity to ensure an optimal
      treatment for pregnant women with asthma, in order to prevent fetal hypoxia, and
      the precaution linked to any drug prescription during pregnancy. Thus, the use of
      topical corticosteroids remains the first choice for asthma as well as rhinitis.
      Inhaled beta2-agonists are also recommended. Systemic corticosteroids may however
      be prescribed without hesitation when their use is required for asthma treatment.
      It is also interesting to note that oral second-generation antihistamines are
      currently allowed during pregnancy and breast feeding. This type of
      antihistamines is indeed to be preferred to first-generation ones that generate
      more side-effects and generally are thus not to be prescribed during breast
      feeding.

PMID- 17552257
TI  - [Pratical aspects of anti-Ige therapy in severe allergic asthma].
AB  - Omalizumab is an anti-IgE monoclonal antibody, available on the swiss market
      since november 2006, with the indication as add on therapy for the treatment of
      poorly controlled severe persistent allergic asthma. These severe asthmatics
      consume a great share of the resources dedicated to asthma. Many randomised
      controlled studies have demonstrated the efficacy of omalizumab in reducing
      exacerbation and requirement of inhaled corticosteroids and in improving quality
      of life. Omalizumab is reimbursed in Switzerland for adults and children over 12
      years of age, with objective markers of atopy and total IgE ranging between 30 et
      700 UI/ml. Only allergists and respiratory physician can prescribe this drug in
      Switzerland. This reyiew focuses on the rationale, indications and practical use
      of anti-IgE therapy.

PMID- 17552258
TI  - [Large vessel vasculitis: giant cell arteritis and Takayasu arteritis].
AB  - Giant cell arteritis (GCA) and Takayasu arteritis (TA) are both chronic
      granulomatous vasculitis of unknown aetiology that involve large vessels. Signs
      and symptoms are related to the affected vessels: the primary branches of the
      aorta in TA and the extra-cranial branches of the external carotid artery in GCA.
      TA affects women under 40 of all ethnic origins with a greater prevalence in
      Asia, whereas GCA affects elderly of caucasian ancestry. In both diseases the
      diagnosis and follow up are rendered difficult by the absence of specific marker
      but advances in imaging technologies such as angio-MRI and PET/CT are very
      promising. Corticosteroids still represent the basis of treatment, most often
      alone in GCA and usually in association with another immunosuppressive drug in
      TA.

PMID- 17552259
TI  - [Anti-HLA antibody detection and rejection in kidney transplantation: impact of
      the new technologies].
AB  - In kidney transplantation, hyperacute rejection is mediated by anti-HLA antibody
      which are also responsible for antibody-mediated acute rejection. In addition
      anti-HLA antibody are also implicated in the physiopathological mechanism of
      chronic rejection. The gold standard methodology to detect anti-HLA antibody is
      based on the complement-dependant-cytotoxicity. This technic is neither specific
      nor sensitive. New powerful technologies, which are specific and very sensitive,
      have been developed like Elisa and flow cytometer with fluorescent micro-beads to
      detect anti-HLA antibody. In this article, we review the importance of anti-HLA
      antibody in humoral rejection. We also discussed the clinical relevance of the
      detection of anti-HLA antibody by these new approaches.

PMID- 17552260
TI  - [Monitoring hypoglycemia in elderly diabetic patients: a prospective study].
AB  - Hypoglycaemia is often underestimated in the elderly diabetic patient, as
      clinical manifestations of hypoglycaemia in these patients are frequently
      atypical. This prospective study, enrolling 100 elderly diabetic patients (age:
      79.3 years) shows a great incidence of hypoglycaemic events (24%) during the
      first day of hospitalisation in a geriatric unit. According to the results of
      this study, common risk factors for hypoglycaemia in the elderly (advanced age,
      insulin therapy, renal insufficiency, polymedication, fragility) have no
      significant predictive value. It appears that screening for risk factors is not
      enough to prevent hypoglycaemia in the elderly diabetic patient, thereby a
      careful monitoring of glycaemia during the first days (and nights) of
      hospitalisation is required. Renewed efforts at better defining appropriate
      therapeutic goals, taking into account the patient's life expectancy and
      comorbidities, will help prevent the occurrence of hypoglycaemia in the elderly
      diabetic patient.

PMID- 17552261
TI  - [Two sides of advertising of pharmaceuticals: promotion and accountability].

PMID- 17552262
TI  - [Drug therapy for Rett syndrome].

PMID- 17552264
TI  - [Wine in literature].

PMID- 17552263
TI  - [Nicolas Sarkozy and the relationship between genes and behavior].

PMID- 17552265
TI  - [Medicalization without physicians].

PMID- 17552266
TI  - [Diagnosis in dermatology].
AB  - We summarize here some of the specificities of diagnosis in dermatology for the
      general practitioner. Starting with clinical cases, we analyze the steps that the
      dermatologist uses to diagnose skin disorders. The initial clinical examination
      of primary and secondary skin lesions leads to a differential diagnosis.
      Subsequently, laboratory techniques such as direct microscopy, histopathology as
      well as recent techniques derived from the field of molecular biology allow us to
      confirm the initial clinical diagnosis. We demonstrate here with a few examples
      of increasing complexity how to incorporate new laboratory techniques into the
      field of clinical dermatology and propose an integrated view of modem dermatology
      where clinical examination and laboratory techniques enable us to achieve a
      correct diagnosis of dermatological diseases.

PMID- 17552267
TI  - [Pediatric psoriasis].
AB  - Psoriasis is a cutaneous inflammatory disorder that may be seen in childhood,
      sometimes complicated by serious forms. The diagnosis is often more difficult
      than in adults, because initial lesions may be atypical or pauci-symptomatic.
      Psoriasis is a chronic disease, with a prognosis worse than atopic dermatitis;
      patients and their family generally need long term therapy and supportive care.
      The treatment is not different from that of the adult, but is less studied and
      less validated by specific pediatric controlled studies.

PMID- 17552268
TI  - [Serious Staphylococcus aureus skin infections that are Panton-Valentine
      leukocidin positive: a new challenge].
AB  - The growing emergency of infections with community-acquired methicillin-resistant
      Staphylococcus aureus (CA-MRSA) secreting the Panton-Valentine toxin (PVL) has
      become a serious health problem with epidemic proportions. These bacteria are
      responsible of severe skin and soft tissue infections, with frequently necrotic
      lesions, and severe necrotizing pneumonias. CA-MRSA, the spreading of which is
      particularly observed in certain risk populations (such as schoolchildren, prison
      inmates, exposure to healthcare establishment) is now also implicated in
      nosocomial infections. Besides adequate antibiotic treatment, surgical drainage
      and incision of the skin lesions are important. It is therefore essential to
      respect elementary hygiene rules in order to prevent the acquisition and
      transmission of CA-MRSA.

PMID- 17552269
TI  - [Toxic epidermal necrolysis].
AB  - The toxic epidermal necrolysis (TEN) is an immunologic reaction in the skin with
      apoptosis of keratinocytes: most cases are reactions against drugs. The main
      features of this reaction are a separation of the epidermis and erosions of the
      mucus membranes, associated with a reduction of the general condition with kidney
      and liver failure. This leads to problems similar to those observed in severely
      burned patients. The mortality high of patients with TEN can be reduced, if the
      responsible drug is immediately withdrawn and if the patient is treated in a
      specialized burns intensive care unit. The medical treatment to stop the chain
      reaction of apoptosis is still under discussion. Through a case report, this
      article will focus on the complexity of the treatment of patients with TEN and
      will point out the importance of a multidisciplinary approach.

PMID- 17552270
TI  - [Follow-up of melanoma lesions].
AB  - Due to the early diagnosis, melanomas can be diagnosed in early stages. Most
      melanomas tend not to show morphological criteria of malignancy in the very early
      stages. They rather resemble benign moles. For patients with hundreds of atypical
      lesions, follow-up examinations using digital dermoscopy are very helpful. This
      technique enables the physician to monitor lesions and to detect microscopic
      change. Lesions with microscopic change are thought to be high risk lesions and
      should be removed this will represent important savings for the health system
      because this will allow to make the diagnosis of melanoma in earlier stages and
      to save costs for unnecessary surgery. In this article we are going to review the
      technique.

PMID- 17552271
TI  - [Treatment of varicose veins and telangiectasias].
AB  - Dermatologic surgery has evolved enormously within the past few years especially
      for the treatment of varicose veins and telangiectasias. New minimally-invasive
      techniques have been developed: lasers, echo-sclerosis, surgery with tumescent
      anesthesia and endovascular treatment of saphenous veins. Most interventions can
      be performed with local anesthesia in the office setting. These new treatments
      are intended to decrease the risks of surgery, reduce medical costs and the
      necessity for hospitalization, and improve functional and esthetic results.

PMID- 17552272
TI  - [Brain tumors in children: diagnosis and therapy].

PMID- 17552273
TI  - [Trafficking for organ transplants].

PMID- 17552274
TI  - [Blood and the razor].

PMID- 17552275
TI  - [The demonstrated impact of auto pollution on Dutch children].

PMID- 17552276
TI  - [Nature and nurture].

PMID- 17552277
TI  - [Violence and humanity].

PMID- 17552278
TI  - [Histone methylation in the formation of higher-order chromatin structure].

PMID- 17552279
TI  - [Spatio-temporal regulation of ERK1/2 MAP kinase].

PMID- 17552280
TI  - [Molecular mechanisms regulating neuronal polarity via phosphorylation
      signaling].

PMID- 17552281
TI  - [Roles for ubiquitylation in DNA repair].

PMID- 17552282
TI  - [Protein modifications in neurodegenerative disorders].

PMID- 17552283
TI  - [Neuronal identity and axonal projection of olfactory sensory neurons].

PMID- 17552284
TI  - [Molecular dynamics of CCA-addition by CCA-adding enzyme].

PMID- 17552285
TI  - [Turning ES cells into tissue stem cells of endodermal lineages].

PMID- 17552286
TI  - Remarkable efficacy of thermal therapy for Sjogren syndrome.

PMID- 17552287
TI  - Volume measurement of the left ventricle in children using real-time three
      dimensional echocardiography: comparison with ventriculography.
AB  - OBJECTIVES: Recently, a real-time three-dimensional echocardiography (RT3DE)
      volume scanning technique was developed and used clinically. For precise
      ventricular volumetry, independent of mathematical assumptions, imaging
      techniques such as three-dimensional echocardiography are required in children
      with heart disease. This study evaluated whether RT3DE is suitable for left
      ventricular volumetry in children, and whether left ventricular volumes measured
      by RT3DE correlate sufficiently well with those measured by left ventriculography
      (LVG). METHODS: Twenty-five children with heart disease, 17 boys and 8 girls aged
      from 8 months to 18 years (mean age 5.9 +/- 5.3 years), underwent cardiac
      catheterization at our institution. RT3DE was performed within 30 min after LVG
      using the Philips SONOS 7500 ultrasound system with an electronic sector probe
      consisting of a X 4 matrix phased array transducer (center frequency of 2-4 MHz).
      Ultrasound images of the ventricle were calculated offline using TomTec 4D Cardio
      View RT 1.2 software. Left ventricular volumes by LVG were calculated using
      Siemens Hicor T.O.P. Finally, the left ventricular volumes by RT3DE and LVG were
      compared. RESULTS: Left ventricular volumes measured by RT3DE correlated and
      agreed well with those measured by LVG(r = 0.996, Y = 0.566 + 0.964 X, mean
      difference -0.29 +/- 1.90ml; left ventricular end-systolic volume, r = 0.979, Y=
      0.187 + 0.897 X, mean difference -6.76 +/- 10.58ml; left ventricular end
      diastolic volume). CONCLUSIONS: RT3DE is suitable for left ventricular volumetry
      in children. There was a good correlation between RT3DE and LVG, but the volume
      of left ventricular end-diastolic volume estimated by RT3DE was smaller than that
      by LVG.

PMID- 17552288
TI  - Association between silent ST segment depression in exercise electrocardiography
      and insulin resistance in obese subjects.
AB  - OBJECTIVES: This study was designed to clarify the association between ST segment
      depression in exercise electrocardiography (ECG) and insulin resistance in obese
      subjects. METHODS: A multistage graded submaximal exercise stress test on the
      bicycle ergometer was performed under CM5-lead ECG monitoring in 114 obese
      subjects (39 men and 75 women, mean age 50.9 +/- 12.2 years, mean body mass index
      28.6 +/- 3.1 kg/m(2)). RESULTS: In 27 patients showing ST segment depression at
      the final exercise intensities (abnormal ST), insulin resistance index by
      homeostasis model assessment (HOMA-IR) was higher and insulin sensitivity index
      was lower than in the remaining 87 patients with normal ST segment level (normal
      ST). The abnormal ST group showed significantly higher plasma glucose and serum
      insulin levels during the oral glucose tolerance test (OGTT) than the normal ST
      group. The abnormal ST group showed a significantly higher prevalence of
      hypertension, impaired glucose tolerance and metabolic syndrome than the normal
      ST group. Multiple logistic regression analysis showed that insulin resistance as
      evaluated by fasting insulin, sigma insulin during OGTT, HOMA-IR, insulin
      sensitivity index, the levels of uric acid, fasting glucose, systolic blood
      pressure and maximal oxygen uptake were independently associated with ST segment
      depression. CONCLUSIONS: These results suggest that insulin resistance may
      involve pathological ST depression during exercise, as well as previously
      reported factors such as hyperglycemia, hyperuricemia, hypertension and lower
      aerobic capacity.

PMID- 17552289
TI  - Comparison of cardiovascular autonomic responses in elderly and young males
      during head-out water immersion.
AB  - OBJECTIVES: To investigate the cardiovascular autonomic responses to head-out
      water immersion in thermoneutral water. The effects of immersion levels (neck,
      chest, navel) and breathing frequencies (4, 6, 10, 15 times/min) were compared
      with in ambient air and spontaneous breathing as a control. METHODS: Spectral
      analysis of heart rate variability was recorded in 11 young (mean age 20 +/- 1
      years) and 11 elderly (mean age 68 +/- 6 years) healthy male subjects during
      water immersion. Modeling was employed to estimate the time course of low
      frequency (LF) and high-frequency (HF) power and the ratio of LF to HF power of
      heart rate variability. RESULTS: In the young group, stroke volume and cardiac
      output during navel level water immersion manifested a much greater increase than
      during chest and neck level water immersion. Systolic blood pressure and total
      peripheral resistance decreased significantly in response to water immersion. The
      elderly group, however, showed lesser attenuation of stroke volume and cardiac
      output. Ectopic arrhythmias occurred in only the elderly. The elderly group
      showed significantly lower and higher amplitudes of HF and LF/HF components of
      heart rate variability due to water immersion and breathing frequency changes.
      CONCLUSIONS: These findings suggest differential changes in cardiovascular
      autonomic responses between the young and elderly groups. These changes in
      integrative cardiovascular autonomic responses may account for the increased risk
      of ectopic arrhythmias in elderly people during water immersion. Water immersion
      model could be utilized to know circulatory regulation during bathing.

PMID- 17552290
TI  - [Infusion therapy at outpatient clinic in chronic end-stage heart failure].
AB  - OBJECTIVES: To determine whether drug infusions at ambulatory clinic in patients
      with end stage congestive heart failure are safe and reduce the period of
      hospitalization. METHODS: Between May 2000 and November 2006, 21 ambulatory
      patients with end stage congestive heart failure were treated with infusions of
      the natriuretic peptide, carperitide (6 patients, 43 infusions of mean 0.033
      microg/kg/min for mean 3.7 hr), the phosphodiesterase inhibitor, olprinone (19
      patients, 75 infusions of mean 0.11 microg/kg/min for mean 3.8 hr), or the
      catecholamines, dopamine or dobutamine(5 patients, 89 infusions of mean 3.3
      microg/kg/min for mean 3.2 hr). RESULTS: Systolic and diastolic blood pressure
      was lower after infusion of carperitide, whereas catecholamines increased
      systolic blood pressure and heart rate (all differences from baseline p <
      0.0001). Olprinone changed neither blood pressure nor heart rate. No adverse
      effect was observed, including arrhythmias or change in blood pressure requiring
      cessation of drug infusion. Mean urinary output per infusion was 979 ml for
      carperitide, 720ml for olprinone, and 594ml for catecholamines. There was no
      correlation between mean urinary output and dose of furosemide administered
      during intermittent infusion therapy. There was a close correlation between pre
      infusion blood pressure and urinary output(systolic: p < 0.05; diastolic: p <
      0.0001). Infusion therapy reduced the length of hospitalization (p < 0.05) in 7
      patients from April 2005. CONCLUSIONS: Ambulatory, low-dose infusion therapy may
      not decrease the mortality of patients in end-stage congestive heart failure, but
      was safe and might represent an acceptable end-of-life therapeutic option.

PMID- 17552291
TI  - [Diabetic retinopathy as a guide for treatment strategy in coronary
      revascularization: from the perspective of cardiac surgeons].

PMID- 17552292
TI  - Rare survival in a patient with severe complications of acute myocardial
      infarction: a case report.
AB  - A 50-year-old man presented with acute myocardial infarction. Coronary
      angiography showed the left anterior descending artery (segment 6) was totally
      occluded. Direct percutaneous transluminal coronary angioplasty was performed,
      but a distal embolism occurred by the procedure. Consequently, he suffered
      cardiogenic shock and sustained ventricular tachycardia/fibrillation which
      exacerbated his condition. Finally, the patient was successfully treated with
      catheter ablation and cryosurgery to control the incessant ventricular
      arrhythmias, and partial left ventricular volume reduction and coronary artery
      bypass grafting to improve contractile performance. His left ventricular
      contractility did not improve, but the incessant ventricular arrhythmias could be
      controlled. His condition remarkably improved and he was discharged on foot. This
      patient with severe complications of acute myocardial infarction showed unusually
      good response and recovery.

PMID- 17552293
TI  - Systemic lupus erythematosus initially manifesting as acute pericarditis
      complicating with cardiac tamponade : a case report.
AB  - A 23-year-old woman was admitted with progressive shortness of breath.
      Echocardiography showed a large volume of pericardial effusion, which indicated
      cardiac tamponade. Yellowish and puriform fluid with increased white blood cell
      count (neutrophil dominant) was aspirated, but antibiotics were ineffective.
      Further examination revealed the presence of positive anti ds-DNA antibody, anti
      SS-A antibody and anti Sm antibody, resulting in a diagnosis of systemic lupus
      erythematosus. Her condition was smoothly improved by predonisolone
      administration. Cardiac tamponade is a rare initial manifestation of systemic
      lupus erythematosus.

PMID- 17552294
TI  - [Recurrent ampulla cardiomyopathy showing prolonged sympathetic nerve function
      disorder: a case report].
AB  - A 58-year-old woman with chronic renal failure had been undergoing maintenance
      hemodialysis. Ampulla cardiomyopathy recurred in association with prolonged
      sympathetic nerve function disorder. Periodical evaluation of the patient's
      condition using 123I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy was
      continued since the first attack at age 55 years. The initial washout rate was
      high at 58.3%, and was still high at 33.0% when she was discharged following
      improvement in wall motion, and remained high at 45.4% 1 year after discharge.
      Recurrence occurred at age 58 years, when a high washout rate of 48.6% was
      observed. High washout rate values of 49.5% and 40.1% were also observed 2 and 9
      months after discharge, respectively, following improvement in wall motion
      abnormalities. 123I-MIBG can be used to assess the course of recurrent ampulla
      cardiomyopathy, and can objectively evaluate sympathetic nerve function
      disorders. This interesting case suggests that sympathetic nerve function
      disorder is closely related to the pathophysiology of this disorder.

PMID- 17552295
TI  - [Multiple atrial ball thrombi with stalk mimicking myxoma without valve disease:
      a case report].
AB  - A 77-year-old man with atrial tumors was admitted to our hospital. He had no
      history of dyspnea, palpitation, or chest pain. He had a history of hypertension
      and atrial fibrillation without valve disease. Transthoracic and transesophageal
      echocardiography showed floating ball tumors with stalks from the right atrium
      (28 X 31 mm), the interatrial septum (16 X 11 mm), and the left atrial appendage
      (14 X 8 mm). The tumors were surgically removed and histologic examination of
      these tumors confirmed organization thrombus. This case of multiple atrial ball
      thrombi illustrates the problems with differentiation of myxoma and thrombus.

PMID- 17552296
TI  - [A 53-year-old man with diastolic heart murmur and abnormal blood flow in the
      main pulmonary artery].

PMID- 17552297
TI  - [Predictive factors for treatment outcome of temporomandibular disorder patients.
      A retrospective study].
AB  - Not all temporomandibular disorder patients respond positively to the treatment
      given. The aim of this retrospective investigation was to study the possible
      associations between some clinical and psychological factors, recorded at the
      patient's first visit, and treatment outcome. Data of 102 patients referred to
      the department's clinic was collected. In 51 patients the treatment was
      unsuccessful (no or only partial relief of pain), in 51 patients, matched for age
      and gender, the treatment was successful (complete relief of pain complaints).
      Logistic regression modeling (p = 0.008, explained variance = 15%; sensitivity =
      59%; specificity = 57%) showed that an unsuccessful treatment was associated with
      more preceding treatments and more jaw-disability, a successful treatment with
      higher scores on the graded chronic pain severity scale. In conclusion, the
      results of this study suggest that some predictive factors may be helpful in
      identifying patients who are at risk of being resistant to the usual treatment
      given.

PMID- 17552298
TI  - [Post-academic dental specialties. 10. Post-academic specialization in pediatric
      dentistry].
AB  - As is the case with other dental disciplines, pediatric dentistry has moved in
      the direction of a specialized educational programme. After a cautious start at
      the end of the last century, the European Academy of Paediatric Dentistry (EAPD)
      and the Dutch Association of Pediatric Dentistry have now recognized the
      previously existing programme at the Academic Center for Dentistry Amsterdam
      (ACTA) and a register for dentists-pedodontologists has been established.
      Recently, about 30 dentist-pedodontologists have received their certification.
      They work in private practice, pedodontic secondary dental practice and centers
      for special dental care as well as in university (hospital) clinics. They
      willingly assist the general dental practitioner with advice and active
      treatments.

PMID- 17552299
TI  - [Post-academic dental specialties. 11. Discomfort during atraumatic restorative
      treatment (ART) versus conventional restorative treatment].
AB  - Although Atraumatic Restorative Treatment (ART) claims to be a patient-friendly
      method of treatment, little scientific proof of this is available. The aim of
      this study, therefore, was to acquire a reliable measurement of the degree of
      discomfort which children experience during dental treatment performed according
      to the ART approach and during the conventional method. A number of 403
      Indonesian schoolchildren were randomly divided into 2 groups. In each child, one
      class II restoration was carried out on a deciduous molar either by means of ART
      or the use of rotary instruments (750 rpm). Discomfort scores were determined
      both by physiological measurements (heart rate) and behavioral observations
      (Venham scale). Venham scores showed a marked difference between the 2 groups,
      whereas heart rate scores only differed significantly during deep excavation. A
      correlation was found between Venham scores and heart rate measurements. Sex,
      initial anxiety and performing dentist were shown to be confounding variables. In
      conclusion it can be said that children treated according to the ART approach
      experience less discomfort than those treated with rotary instruments.

PMID- 17552300
TI  - [Dissertations 25 years after date. 15. Remineralization of human enamel].
AB  - Remineralization of human enamel is an important issue in the prevention of
      caries. Fluoride has an important influence on the remineralization process. A
      great deal of research has been done into the role played by the method of
      application and by the concentration and type of fluoride. In the clinical study
      of this dissertation the process of remineralization of lesions in human enamel
      was longitudinally followed in vivo during a period of 3 months. Both the
      remineralization in the surface softened enamel lesion and the subsurface enamel
      lesion of human enamel were studied. In addition, attention was devoted
      especially to the influence of fluoride on this remineralization. The results
      indicated that the use of a 1,500 ppm fluoridated NaF toothpaste was more
      effective on the remineralization process than the use of a 50 pmm NaF
      mouthrinse. Important is the fluoride gradient in the enamel lesion, and in
      particular the fact that fluoride reaches the lesion front. This most likely
      accounts for the remineralization efficiency.

PMID- 17552301
TI  - [Kahler's disease. Multiple myeloma].
AB  - Kahler's disease, multiple myeloma, is a malignant condition of unbridled
      multiplication of plasma cells in bone marrow. Clinical features are anaemia,
      pain in the affected bones, spontaneous bone fractures and increased infection
      susceptibility. In the final stage of the disease severe renal failure can occur.
      With the present chemotherapy a good response is seen in 50-70% of patients, but
      complete response occurs only in a minority of patients. Radiotherapy is often
      used in addition to chemotherapy. Bisphosphonates are used to inhibit osteolysis
      and to prevent complications associated with osteolysis. Recently, an association
      was found between use of bisphosphonates and jaw osteonecrosis. In order to
      minimize the risk of complications, it is advocated to be in touch with the
      patients haematologist before starting an invasive oral treatment.

PMID- 17552302
TI  - Pilots' monitoring strategies and performance on automated flight decks: an
      empirical study combining behavioral and eye-tracking data.
AB  - OBJECTIVE: The objective of the study was to examine pilots' automation
      monitoring strategies and performance on highly automated commercial flight
      decks. BACKGROUND: A considerable body of research and operational experience has
      documented breakdowns in pilot-automation coordination on modern flight decks.
      These breakdowns are often considered symptoms of monitoring failures even
      though, to date, only limited and mostly anecdotal data exist concerning pilots'
      monitoring strategies and performance. METHOD: Twenty experienced B-747-400
      airline pilots flew a 1-hr scenario involving challenging automation-related
      events on a full-mission simulator. Behavioral, mental model, and eye-tracking
      data were collected. RESULTS: The findings from this study confirm that pilots
      monitor basic flight parameters to a much greater extent than visual indications
      of the automation configuration. More specifically, they frequently fail to
      verify manual mode selections or notice automatic mode changes. In other cases,
      they do not process mode annunciations in sufficient depth to understand their
      implications for aircraft behavior. Low system observability and gaps in pilots'
      understanding of complex automation modes were shown to contribute to these
      problems. CONCLUSION: Our findings describe and explain shortcomings in pilot's
      automation monitoring strategies and performance based on converging behavioral,
      eye-tracking, and mental model data. They confirm that monitoring failures are
      one major contributor to breakdowns in pilot-automation interaction. APPLICATION:
      The findings from this research can inform the design of improved training
      programs and automation interfaces that support more effective system monitoring.

PMID- 17552303
TI  - Effects of air traffic geometry on pilots' conflict detection with cockpit
      display of traffic information.
AB  - OBJECTIVE: This experiment attempted to identify the features of air traffic
      geometry that would influence the difficulty and biases of pilots' conflict
      detection using a cockpit display of traffic information (CDTI). BACKGROUND:
      There was previously no systematic study on effects of such features on conflict
      detection using the CDTI. METHOD: Twenty-four pilots viewed dynamic encounters
      between their own aircraft and an intruder aircraft on a simulated CDTI;
      difficulty was varied by the intruder aircraft's distance and time to closest
      point of approach (CPA), relative speed, miss distance at CPA, approach side, and
      conflict angle. Participants estimated the intruder's location at, and its time
      to, CPA. Effects on three estimation error measures were explored: intruder's
      miss distance at CPA, orientation at CPA, and time to CPA. RESULTS: (a)
      Estimation errors increased with slower speeds, longer times to CPA, and longer
      distances to CPA and with longer miss distances at CPA; (b) the best performance
      occurred at a conflict angle of 90 degrees; (c) there was a bias to judge
      conflicts to be more risky than was actually the case; and (d) there was a
      "distance-over-speed" bias, such that two aircraft farther apart and converging
      rapidly were perceived as less risky than when they were closer to each other and
      converging at a slower rate, despite identical time to CPA. CONCLUSION: Pilots'
      conflict detection with CDTI was subject to various errors and biases, which has
      important safety implications. APPLICATION: The design of procedures, displays,
      and decision support tools for the free flight environment needs to take these
      human performance limitations into account.

PMID- 17552304
TI  - Modeling and predicting mental workload in en route air traffic control: critical
      review and broader implications.
AB  - OBJECTIVE: We perform a critical review of research on mental workload in en
      route air traffic control (ATC). We present a model of operator strategic
      behavior and workload management through which workload can be predicted within
      ATC and other complex work systems. BACKGROUND: Air traffic volume is increasing
      worldwide. If air traffic management organizations are to meet future demand
      safely, better models of controller workload are needed. METHOD: We present the
      theoretical model and then review investigations of how effectively traffic
      factors, airspace factors, and operational constraints predict controller
      workload. RESULTS: Although task demand has a strong relationship with workload,
      evidence suggests that the relationship depends on the capacity of the
      controllers to select priorities, manage their cognitive resources, and regulate
      their own performance. We review research on strategies employed by controllers
      to minimize the control activity and information-processing requirements of
      control tasks. CONCLUSION: Controller workload will not be effectively modeled
      until controllers' strategies for regulating the cognitive impact of task demand
      have been modeled. APPLICATION: Actual and potential applications of our
      conclusions include a reorientation of workload modeling in complex work systems
      to capture the dynamic and adaptive nature of the operator's work. Models based
      around workload regulation may be more useful in helping management organizations
      adapt to future control regimens in complex work systems.

PMID- 17552305
TI  - A comparison of human and near-optimal task management behavior.
AB  - OBJECTIVE: The primary contribution of this work is the development of an
      abstract framework to which a variety of multitasking scenarios can be mapped.
      The metaphor of a juggler spinning plates was introduced to represent an operator
      performing multiple concurrent tasks. BACKGROUND: This allowed seeking a
      quantitative model for management of multiple continuous tasks instead of a model
      for completing multiple discrete tasks, which was considered in previous studies.
      METHODS: The multitasking performance of 10 participants in five scenarios was
      measured in a low-fidelity simulator (named Tardast), which was developed based
      on the concept of the juggler metaphor. This performance was then compared with a
      normative model, which was a near-optimal solution to a mathematical programming
      problem found by tabu search heuristics. RESULTS: Tabu outperformed the
      participants overall, although the best individual performance nearly equaled
      that of tabu. It was also observed that participants initially tended to manage
      numerous tasks poorly but that they gradually learned to handle fewer tasks and
      excel in them. CONCLUSION: This suggests that they initially overreacted to the
      penalization associated with poor performance in the software. Participants'
      strategic task management (e.g., what tasks to handle) was more significant in
      obtaining a good score than their tactical task management (e.g., how often to
      switch between two tasks). APPLICATION: Potential applications include better
      design of equipment, procedures, and training of operators of complex systems.

PMID- 17552306
TI  - Mapping candidate within-vehicle auditory displays to their referents.
AB  - OBJECTIVE: This study investigated speech, environmental sounds (naturally
      occurring sounds with arbitrary meanings), auditory icons (natural or synthetic
      sounds with specific meanings), and abstract synthetic warnings as candidates for
      within-vehicle interfaces. BACKGROUND: Auditory displays and warnings must
      satisfy certain criteria, such as being appropriately urgent and commanding
      appropriately fast response times. However, a semiotic analysis suggests that
      displays, as signals interpreted by users, should also be mapped successfully
      onto their referents. METHOD: Response times and accuracy were recorded in a
      computer task of identifying learned mappings of candidate displays to a range of
      referent driving events (such as "headway closing"); perceived urgency and
      pleasantness were assessed separately. RESULTS: Speech and auditory icons
      produced near-ceiling performance in response times and identification accuracy.
      Abstract sounds produced notably slower response times and less accuracy.
      Environmental sounds showed an intermediate pattern of performance for accuracy,
      but the response times were similar to those of the abstract sounds. Speech
      utterances were similarly and consistently rated as pleasant but also of
      intermediate perceived urgency. The three other sound types showed a consistent
      mapping of their perceived urgency to the situational urgency of their referents;
      for these sounds, perceived urgency and pleasantness were negatively correlated.
      CONCLUSION: The results point to the importance of considering the role of signal
      referent relationships in designing auditory displays. APPLICATION: The results
      have applicability for auditory displays in the vehicle interface, whereas the
      theoretical framework is of value in auditory display design in a broader
      context.

PMID- 17552307
TI  - Automation usage decisions: controlling intent and appraisal errors in a target
      detection task.
AB  - BACKGROUND: It was proposed that misuse and disuse often occur because operators
      (a) cannot determine if automation or a nonautomated alternative maximizes the
      likelihood of task success (appraisal errors) or (b) know the utilities of the
      options but disregard this information when deciding to use automation (intent
      errors). OBJECTIVE: This investigation assessed the effectiveness of performance
      feedback, a procedure developed to attenuate appraisal errors, and scenario
      training, an intervention designed to decrease intent errors. METHODS: Operators
      given feedback were told how many errors they and an automated device made on a
      target detection task. Scenario training took operators through the thought
      processes of optimal decision makers after the utilities of the automated and
      nonautomated alternatives had been determined. Following 200 training trials,
      participants chose between relying on their observations or an automated device.
      RESULTS: There was little misuse, but disuse rates were high (84%) among
      operators receiving neither feedback nor scenario training. Operators paired with
      a more accurate machine and given feedback made approximately twice as many
      errors as the automated device. Nevertheless, intent errors were commonplace; 55%
      of the operators who received feedback without scenario training did not rely on
      automation. Feedback effectiveness was enhanced when used in conjunction with
      scenario training; the disuse rate decreased to 29%. CONCLUSION: A combination of
      feedback and scenario training was more effective in mitigating disuse than
      either intervention used in isolation. APPLICATION: An important application of
      these findings is that operator training programs should incorporate techniques
      to control intent and appraisal errors.

PMID- 17552308
TI  - A relation between dynamic strength and manual materials-handling strategy
      affected by knowledge of strength.
AB  - OBJECTIVE: We studied the relation between dynamic (isokinetic) strength and the
      batch-assorting strategy to initiate a manual materials-handling task and the
      effect of knowledge of strength on that relation. BACKGROUND: The debated,
      complex relationship between muscular strength and the risk of injury can be
      better understood from a behavioral perspective by examining performance
      strategies in physical acts such as lifting. METHODS: Thirty-two participants (16
      men and 16 women) were first tested for their isokinetic strengths of trunk
      extension, knee extension, shoulder extension, and shoulder abduction. The
      participants were then divided into two groups, one provided with knowledge
      feedback of their strength testing results and the other not provided with such
      feedback. Participants subsequently performed the same load-handling task in
      which they carried batches of various weight plates while allowed to assort
      batches of more than one plate into any combination. RESULTS: Dynamic strength,
      as represented by a total isokinetic strength score, and knowledge feedback both
      had significant effects on measures quantifying the batch-assorting strategy.
      CONCLUSION: Individuals with greater strength tended to adopt a strategy
      corresponding to a heavier load per carry and fewer carries per batch. Receiving
      knowledge feedback evoked a tendency toward handling a heavier load, and this
      tendency was more salient in the weaker individuals. APPLICATION: Potential
      applications include the use of strength testing in worker selection and training
      as well as in job design to promote better strategies of balancing productivity
      and injury prevention.

PMID- 17552309
TI  - Evaluation of fall arrest harness sizing schemes.
AB  - OBJECTIVE: This paper evaluated harness sizing schemes and anthropometric
      criteria for harness design applications. BACKGROUND: Updated harness sizing
      systems are needed to accommodate diverse populations in the current workforce.
      METHOD: Three-dimensional torso scan data and human-harness interfaces from 108
      women and 108 men were digitally captured. Abounding box approach was employed to
      quantify the effect of torso shape and size on fall harness fit. RESULTS: A
      logistic regression model with eight equations was developed and tested to
      classify more than 96% of participants to the best-fitting size. CONCLUSION:
      Study outcomes suggested an alternative system of two sizes for women and three
      sizes for men over the current four-size unisex system. In addition, thigh strap
      angle and back D ring location could be utilized along with current harness
      static fit test criteria to further enhance postfall harness fit predictions.
      APPLICATION: This research could help reduce the risk of worker injury resulting
      from poor fit, improper size selection, or failure to don the harness properly.

PMID- 17552310
TI  - Icon identification in context: the changing role of icon characteristics with
      user experience.
AB  - OBJECTIVE: This research examined the relative importance of icon characteristics
      in determining the speed and accuracy of icon identification. BACKGROUND: Studies
      to date have focused on the role of one or two icon characteristics when users
      first experience an icon set. This means that little is known about the relative
      importance of icon characteristics or how the role of icon characteristics might
      change as users gain experience with icons. METHODS: Thirty participants carried
      out an icon identification task over a long series of trials to simulate learning
      through experience. Icon characteristics investigated included semantic distance,
      concreteness, familiarity, and visual complexity. RESULTS: Icon characteristics
      were major determinants of performance, accounting for up to 69% of the variance
      observed in performance. However, the importance of icon characteristics changed
      with experience: Semantic distance is crucial initially while icon-function
      relationships are learned, but familiarity is important later because it has
      lasting effects on access to long-term memory representations. CONCLUSION: These
      findings suggest that icon concreteness may not be of primary importance when
      identifying icons and that semantic distance and familiarity may be more
      important. APPLICATION: Designers need to take into account icon characteristics
      other than concreteness when creating icons, particularly semantic distance and
      familiarity. The precise importance of the latter characteristics will vary
      depending on whether icons are rarely encountered or frequently used.

PMID- 17552311
TI  - Color coding of control room displays: the psychocartography of visual layering
      effects.
AB  - OBJECTIVE: To evaluate which of three color coding methods (monochrome, maximally
      discriminable, and visual layering) used to code four types of control room
      display format (bars, tables, trend, mimic) was superior in two classes of task
      (search, compare). BACKGROUND: It has recently been shown that color coding of
      visual layers, as used in cartography, may be used to color code any type of
      information display, but this has yet to be fully evaluated. METHOD: Twenty-four
      people took part in a 2 (task) x 3 (coding method) x 4 (format) wholly repeated
      measures design. The dependent variables assessed were target location reaction
      time, error rates, workload, and subjective feedback. RESULTS: Overall, the
      visual layers coding method produced significantly faster reaction times than did
      the maximally discriminable and the monochrome methods for both the search and
      compare tasks. No significant difference in errors was observed between
      conditions for either task type. Significantly less perceived workload was
      experienced with the visual layers coding method, which was also rated more
      highly than the other coding methods on a 14-item visual display quality
      questionnaire. CONCLUSION: The visual layers coding method is superior to other
      color coding methods for control room displays when the method supports the
      user's task. APPLICATION: The visual layers color coding method has wide
      applicability to the design of all complex information displays utilizing color
      coding, from the most maplike (e.g., air traffic control) to the most abstract
      (e.g., abstracted ecological display).

PMID- 17552312
TI  - Recovery from virtual environment exposure: expected time course of symptoms and
      potential readaptation strategies.
AB  - OBJECTIVE: This study investigated potential means of facilitating a return to
      normal functioning following virtual environment (VE) exposure using a peg-in
      hole exercise in recalibrating hand-eye coordination, a targeted gait movement
      (rail walking) in recalibrating vestibular (i.e., postural) aftereffects, and
      natural decay. BACKGROUND: Despite technology advances and considerable efforts
      focused on the identification and quantification of VE aftereffects, few have
      addressed means for recuperation, the focus of the current study. METHOD: After
      15 min-60 min of VE exposure and recalibratory exercises, hand-eye coordination
      and postural stability were assessed electronically, the former via a 3-D measure
      capturing pointing errors, and the latter by head and body oscillations while
      standing in the tandem Romberg position. Both measurements were collected
      immediately after VE exposure and every 15 min up to 1 hr thereafter. RESULTS:
      Participants (more than 900 college students) who experienced the peg-in-hole
      readaptation strategy had a significant decrease (p < 0.000 in pointing errors
      following the exercise; the other two methods (i.e., rail walking, natural decay)
      showed no significant change. For posture, all groups showed significant
      improvement during the 15 minutes after VE exposure, yet none returned to
      baseline by 1 hr postexposure. CONCLUSION: Although hand-eye coordination
      readaptation strategies showed noticeable effects immediately after they were
      performed, aftereffects were not completely eliminated after 1 hr; hence further
      research on readaptation strategies is essential to achieve more substantial
      recalibratory gains in hand-eye coordination and posture. Additionally, hand-eye
      coordination and vestibular aftereffects may require a period exceeding the VE
      immersion time in order to recover. APPLICATION: These findings may serve as a
      guide in the development of monitoring policies following VE exposure.

PMID- 17552313
TI  - Interaction with an immersive virtual environment corrects users' distance
      estimates.
AB  - OBJECTIVE: Two experiments examined whether prior interaction within an immersive
      virtual environment (VE) enabled people to improve the accuracy of their distance
      judgments and whether an improved ability to estimate distance generalized to
      other means of estimating distances. BACKGROUND: Prior literature has
      consistently found that users of immersive VEs underestimate distances by
      approximately 50%. METHOD: In each of the two experiments, 16 participants viewed
      objects in an immersive VE and estimated their distance to them by means of
      blindfolded walking tasks before and after interacting with the VE. RESULTS: The
      interaction task significantly corrected users' underestimation bias to nearly
      veridical. Differences between pre- and post-interaction mean distance estimation
      accuracy were large (d = 4.63), and significant (p < .001), and they generalized
      across response task. CONCLUSION: This finding limits the generality of the
      underestimation effect in VEs and suggests that distance underestimation in VEs
      may not be a road block to the development of VE applications. APPLICATION:
      Potential or actual applications of this research include the improvement of VE
      systems requiring accurate spatial awareness.

PMID- 17552314
TI  - Evaluation of six night vision enhancement systems: qualitative and quantitative
      support for intelligent image processing.
AB  - OBJECTIVE: An evaluation study was conducted to answer the question of which
      system properties of night vision enhancement systems (NVESs) provide a benefit
      for drivers without increasing their workload. BACKGROUND: Different infrared
      sensor, image processing, and display technologies can be integrated into an NVES
      to support nighttime driving. Because each of these components has its specific
      strengths and weaknesses, careful testing is required to determine their best
      combination. METHOD: Six prototypical systems were assessed in two steps. First,
      a heuristic evaluation with experts from ergonomics, perception, and traffic
      psychology was conducted. It produced a broad overview of possible effects of
      system properties on driving. Based on these results, an experimental field study
      with 15 experienced drivers was performed. Criteria used to evaluate the
      development potential of the six prototypes were the usability dimensions of
      effectiveness, efficiency, and user satisfaction (International Organization for
      Standardization, 1998). RESULTS: Results showed that the intelligibility of
      information, the easiness with which obstacles could be located in the
      environment, and the position of the display presenting the output of the system
      were of crucial importance for the usability of the NVES and its acceptance.
      CONCLUSION: All relevant requirements are met best by NVESs that are positioned
      at an unobtrusive location and are equipped with functions for the automatic
      identification of objects and for event-based warnings. APPLICATION: These design
      recommendations and the presented approach to evaluate the systems can be
      directly incorporated into the development process of future NVESs.

PMID- 17552315
TI  - Lane-change detection using a computational driver model.
AB  - OBJECTIVE: This paper introduces a robust, real-time system for detecting driver
      lane changes. BACKGROUND: As intelligent transportation systems evolve to assist
      drivers in their intended behaviors, the systems have demonstrated a need for
      methods of inferring driver intentions and detecting intended maneuvers. METHOD:
      Using a "model tracing" methodology, our system simulates a set of possible
      driver intentions and their resulting behaviors using a simplification of a
      previously validated computational model of driver behavior. The system compares
      the model's simulated behavior with a driver's actual observed behavior and thus
      continually infers the driver's unobservable intentions from her or his
      observable actions. RESULTS: For data collected in a driving simulator, the
      system detects 82% of lane changes within 0.5 s of maneuver onset (assuming a 5%
      false alarm rate), 93% within 1 s, and 95% before the vehicle moves one fourth of
      the lane width laterally. For data collected from an instrumented vehicle, the
      system detects 61% within 0.5 s, 77% within 1 s, and 84% before the vehicle moves
      one-fourth of the lane width laterally. CONCLUSION: The model-tracing system is
      the first system to demonstrate high sample-by-sample accuracy at low false alarm
      rates as well as high accuracy over the course of a lane change with respect to
      time and lateral movement. APPLICATION: By providing robust real-time detection
      of driver lane changes, the system shows good promise for incorporation into the
      next generation of intelligent transportation systems.

PMID- 17552316
TI  - Development and evaluation of a just-in-time support system.
AB  - OBJECTIVE: To lay the foundation for a framework of just-in-time support (JITS)
      for novices dealing with urgent, unfamiliar tasks, and to evaluate a JITS system.
      BACKGROUND: More than 350,000 people die annually of cardiac arrest in the United
      States. In response, automated defibrillators are advocated that, unfortunately,
      do not provide important respiratory support. This paper presents elements of a
      framework for a JITS system that instructs a lay responder to follow a treatment
      protocol for integrating respiratory support with the use of an automatic
      external defibrillator. METHOD: We simulated a medical emergency using a high
      fidelity patient simulator and asked participants to care for the patient.
      RESULTS: When using a paper-based NASA treatment protocol, participants made more
      errors and took longer to stabilize the injured person than when using the JITS
      system. CONCLUSION: These findings demonstrate the benefit of a JITS system to
      instruct novices in unfamiliar tasks. APPLICATION: The JITS system has the
      potential to improve the treatment outcome of victims of cardiac arrest. The JITS
      framework can be applied to many situations in which novices deal with urgent
      tasks without expertise available.

PMID- 17552317
TI  - E-discovery. Preparing for the coming rise in electronic discovery requests.

PMID- 17552318
TI  - Charting the legal health record.

PMID- 17552319
TI  - Printing electronic records. Managing the hassle and the risk.

PMID- 17552320
TI  - An international certificate in ICD-10 coding. WHO-FIC, IFHRO program offers
      standardized training, coder recognition.

PMID- 17552321
TI  - The value of HIM in and security privacy compliance.

PMID- 17552322
TI  - A subpoena by any other name might not be legal.

PMID- 17552323
TI  - Identity proofing--just a fancy name for verification?

PMID- 17552324
TI  - It's official. HL7's EHR model becomes approved standard.

PMID- 17552325
TI  - Bridging the gap from student to employee.

PMID- 17552326
TI  - Health data access, use, and control.

PMID- 17552327
TI  - Applying facility E/M codes in the hospital emergency department.

PMID- 17552328
TI  - IRF PPS coding challenges.

PMID- 17552329
TI  - Delivering the EHR.

PMID- 17552330
TI  - As much about costs as about quality.

PMID- 17552331
TI  - Mental health parity gets closer to reality.

PMID- 17552332
TI  - Medication therapy management may finally enter the mainstream.

PMID- 17552333
TI  - Most docs break bread with pharma.

PMID- 17552334
TI  - Following the leaders.

PMID- 17552336
TI  - Massive databases under construction.

PMID- 17552337
TI  - Keys to diabetes control? Patience, persistence, and perseverance.

PMID- 17552335
TI  - Medicare advantage hits jackpot with private fee-for-service plans.

PMID- 17552338
TI  - The appropriate omalizumab patient.
AB  - Allergy is a significant component in many asthma patients. Omalizumab is a
      monoclonal anti-immunoglobulin E antibody for the treatment of allergic asthma.
      Clinical trials have shown that omalizumab treatment is associated with improved
      symptom control and reduced inhaled corticosteroid doses, resulting in fewer
      exacerbations and reduced utilization of resources. Omalizumab therapy may
      benefit patients who remain uncontrolled or who cannot tolerate standard therapy.

PMID- 17552339
TI  - Plans fall short on immunization rates.

PMID- 17552340
TI  - Introducing the CHR, more like a PHR than an EMR.

PMID- 17552341
TI  - Monoclonal antibody now available to prevent red blood cell breakdown.

PMID- 17552342
TI  - Milder health care spending cycle seen.

PMID- 17552343
TI  - Caring for caregivers. Survey details what nurses need to perform in the midst of
      disaster.

PMID- 17552344
TI  - Hospitals tune in to RFID.

PMID- 17552345
TI  - Understanding what it takes to stop surgical site infections.

PMID- 17552346
TI  - Don't omit manual steps in automated endoscope cleaning.

PMID- 17552347
TI  - Sharpen your focus on endoscope reprocessing.

PMID- 17552348
TI  - Instrument tracking begets efficiency.

PMID- 17552349
TI  - Overcome business culture barriers for successful working relationships.

PMID- 17552350
TI  - Interview with Douglas Hawthorne, FACHE, president and chief executive officer,
      Texas Health Resources. Interview by Kyle L Grazier.

PMID- 17552351
TI  - Regional health information networks and the emerging organizational structures.

PMID- 17552352
TI  - The role of leadership in creating a diversity-sensitive organization.
AB  - The opportunity for personal growth that a focus on DSO development offers
      leaders is compelling, as it provides and requires new experiences and new ideas.
      Seasoned healthcare executives and their organizations are offered the
      opportunity for renewal-to see things in a new light and experience the
      organization, the service area, and each other differently. Researchers at the
      Gallup Organization, based on studies of more than 50,000 leaders in diverse
      industries, have identified the following seven demands of leadership: visioning,
      maximizing values, challenging experiences, mentoring, building a constituency,
      making sense of experience, and knowing one's self (Conchie 2004). To meet these
      demands with courage and conviction in the context of diversity is, perhaps, the
      ultimate healthcare leadership challenge in the foreseeable future.

PMID- 17552353
TI  - Management development: a study of nurse managerial activities and skills.
AB  - This study discusses an activity competency model that may be used to investigate
      the perceived importance of managerial activities and skills required by three
      levels of nurse managers (top, middle, and supervisory management). Our findings
      indicate that the importance of nurse managerial activities differs significantly
      according to the level of nurse management. A set of critical managerial
      activities and skills/knowledge needs for each level of nurse managers was
      identified in the study. These findings provide guidelines for nursing-management
      development programs, training, and career planning. They also can serve as a
      guideline for recruiting and selecting an effective nurse manager.

PMID- 17552354
TI  - Real options reasoning in healthcare: an integrative approach and synopsis.
AB  - For the past 40 years, practitioners and researchers alike have been grappling
      with the natural shortcomings associated with the net present value approach to
      strategic decision making and capital budgeting. Work by scholars in option
      pricing theory has evolved into an alternative perspective on strategic capital
      investments, called "real options." Proponents of real options argue that this is
      a superior way of approaching decision making and capital budgeting, compared
      with other approaches, as it allows for greater strategic flexibility and
      encourages exploration, experimentation, and innovation. Within the healthcare
      literature, articles on real options have focused on pricing these options. This
      article is unique to the healthcare literature as it emphasizes the cognitive or
      strategic aspects of real options. Additionally, this article integrates two
      techniques for applying the real options approach for interested practitioners
      using a hospital's imaging department as an example, while providing scholars
      with additional applications and questions for future research. For
      practitioners, the implications are that thinking of and planning for capital
      investments as real options may create greater strategic and operating
      flexibility than other, more traditional approaches.

PMID- 17552355
TI  - Hospital patient safety: characteristics of best-performing hospitals.
AB  - Hospitals have made slow progress in meeting the Institute of Medicine's patient
      safety goals, and implementation of safety systems has been inconsistent. The
      next logical question is this: What organizational characteristics predict
      greater implementation of patient safety systems, in terms of both extent of
      systems and progress over time? To answer this question, a survey was
      administered to 107 hospitals at two points in time. Data were consolidated into
      seven latent variables measuring progress in specific areas. Using the overall
      measure, Joint Commission-accredited hospitals showed statistically significant
      improvement, as reflected in the sum score (p = .01); nonaccredited hospitals did
      not show statistically significant improvement (p = .21). Joint Commission
      accreditation was the key predictor of patient safety system implementation.
      Management type and urban/rural status were secondary predictors. Several factors
      may account for the strong association between accreditation and patient safety
      system implementation. In 2003, the Joint Commission began tying accreditation to
      patient safety goals. Also, Joint Commission data are now widely available to the
      public and may stimulate hospitals to address safety issues. Healthcare
      executives, hospital trustees, regulators, and policymakers should encourage
      Joint Commission accreditation and reward hospital efforts toward meeting Joint
      Commission standards. The Joint Commission should continually strive to maintain
      evidence-based and state-of-the-art standards that advance the aim of providing
      the best possible care for hospitalized patients.

PMID- 17552356
TI  - Establishment of a communitywide EMS first-responder program.

PMID- 17552357
TI  - Comments regarding: Benzyl isothiocyanate (BITC) induces apoptosis in ovarian
      cancer cells in vitro Kalkunte S, Swamy N, Dizon DS, Brard L. J Exp Ther
      Oncol.5(4):287-300, 2006.

PMID- 17552358
TI  - Simultaneous inhibition of COX-2 and 5-LOX activities augments growth arrest and
      death of premalignant and malignant human lung cell lines.
AB  - The arachidonic acid-metabolizing enzymes cyclooxygenase-2 (COX-2) or 5
      lipoxygenase (5-LOX) are overexpressed during lung carcinogenesis and their end
      products (e.g.; PGE2, 5-HETE, and LTB4) have been implicated in tumor
      development. Recently, COX-2 inhibitors (e.g.; celecoxib) and 5-LOX inhibitors
      (e.g.; MK886 and REV5901) used as single agents have shown promising activities
      in the treatment and chemoprevention of cancer. However, little is known about
      the effects of combinations of these inhibitors. We found that simultaneous
      treatment of premalignant and malignant human lung cell lines with celecoxib,
      MK886, and REV5901 is more potent in growth suppression and induction of cell
      death than single or dual combination of these agents. However, their sensitivity
      to the inhibitors was not directly associated with the expression of COX-2, 5
      LOX, or 5-LOX-activating protein (FLAP), but correlated with the production of
      corresponding metabolites. Furthermore, partial protection of cell death was
      observed when PGE2 and/or 5-HETE was added to cell cultures treated with
      celecoxib, MK886, and REV5901 simultaneously. Our data indicate that a triple
      drug combination of distinct inhibitors of the eicosanoid metabolism at
      clinically feasible concentrations were more effective than each agent alone
      suggesting further investigations.

PMID- 17552359
TI  - A lipid-soluble iron chelator alters cell cycle regulatory protein binding in
      breast cancer cells compared to normal breast cells.
AB  - The lipid-soluble iron chelator desferri-exochelin (D-Exo) causes reversible cell
      cycle arrest in normal human mammary epithelial cells (NHMEC) but triggers
      apoptotic cell death in human breast cancer cells. We studied the effects of iron
      chelation with D-Exo on cell cycle regulatory proteins in cultures of NHMEC and
      MCF-7 breast cancer cells. In co-immunoprecipitation studies, D-Exo inhibited
      binding of cyclins A and E to cyclin dependent kinase 2 (CDK2) in NHMEC, but in
      MCF-7 cells binding of these cyclins to CDK2 was enhanced. D-Exo treatment
      markedly increased expression of p53 and increased binding of p21 to CDK2 in the
      MCF-7 cells but not in NHMEC. Therefore differences in effects of iron chelation
      on cell cycle protein binding in cancer cells compared to normal cells may
      trigger apoptosis in cancer cells while normal breast cells are spared.

PMID- 17552360
TI  - Follicle stimulating hormone receptor (FSHR) antagonist and epithelial ovarian
      cancer (EOC).
AB  - INTRODUCTION: Follicle stimulating hormone receptor (FSHR), a G-protein coupled
      receptor present in granulosa cell of ovary is a unique transmembrane molecule
      pivotal in ovulation process. Its agonist and antagonists has remained the
      subject of interest to the reproductive biologists. It seems worthwhile to see
      what is new research on FSHR and whether they will be of any help in epithelial
      ovarian cancer. METHODS: Pubmed and medline search was made from January 2006 to
      April 2006 to find out current development of FSHR antagonist research and role
      of FSHR in epithelial ovarian cancer RESULTS: Effort to develop FSHR antagonist
      was mainly aimed at peptide antibody development. Breakthrough discovery of
      nonapeptide FSHR antagonist molecules, like suramin, compound 1 and compound 10
      are noted. This is discussed in the context of nonsteroidal contraceptive for
      male and female. FSHR was found to have a distinguished role in precipitation of
      epithelial ovarian cancer. Hence, these antagonists might have a novel role to
      play in their treatment. CONCLUSION: Author proposes the trial of these molecules
      as novel anticancer agents in epithelial ovarian cancer.

PMID- 17552361
TI  - Activation of Src by c-Met overexpression mediates metastatic properties of
      colorectal carcinoma cells.
AB  - Overexpression and/or activation of c-Met, the protein tyrosine kinase receptor
      for the hepatocyte growth factor/scatter factor (HGF/SF), and the protein
      tyrosine kinase, Src, have been implicated in the progression and metastasis of
      human colorectal carcinoma (CRC). Previously, through ribozyme-mediated c-Met
      downregulation, we demonstrated a causal role for c-Met in CRC tumorigenesis and
      the production of liver metastases from the highly metastatic CRC cell line,
      KM20. Analysis of signaling intermediates downstream of c-Met demonstrated a
      specific reduction of Src activity with minimal effect on Erk1/2 and Akt
      following c-Met downregulation. As Src has been shown to upregulate Vascular
      Endothelial Growth Factor (VEGF), we sought to determine if the reduced tumor
      size and incidence could be due to reduced vessel formation in the c-Met
      downregulated clones. Here we show that tumors produced from c-Met downregulated
      cells have significantly reduced vessel density in tumors, correlating with a
      reduction in VEGF production. Additionally, the Src selective inhibitor, PP2,
      significantly reduced basal VEGF production in KM20 parental cells, and this
      effect could be rescued by HGF treatment. PP2 reduced basal proliferation,
      migration, and anchorage-independent growth. Furthermore, PP2 treatment
      demonstrated a dose-dependent decrease in HGF induced migration. In contrast, PP2
      treatment only had a minor effect on HGF induced anchorage-independent growth.
      Collectively, these data demonstrate a significant role for c-Met-mediated Src
      activation in processes involved in CRC tumorigenesis and liver metastasis.

PMID- 17552362
TI  - Decrease of endogenous vascular endothelial growth factor may not affect glioma
      cell proliferation and invasion.
AB  - Vascular endothelial growth factor (VEGF) is abundantly produced by glioma cells
      especially glioblastoma, the most malignant form of astrocytoma. VEGF, a well
      known angiogenic factor, acts in a paracrine fashion on endothelial cells to
      develop tumor vasculature. However, recent studies have found that several tumor
      cells express VEGF receptors, and an autocrine action of VEGF on tumor cells has
      been suggested. To test this hypothesis, three human glioma cell lines (U251n,
      U87 and A172) were checked for VEGF and VEGFR expression. These cells express 0.1
      0.6 ng/ml VEGF165 in cell culture medium within 24 hours. Western blot analysis
      showed that these cells express all of the VEGF receptors, VEGFR-1/Flt-1, VEGFR
      2/KDR, Neuropilin-1 (NRP-1) and Neuropilin-2(NRP-2), even though tyrosine kinase
      receptor VEGFR-2/KDR exhibited baseline levels of expression. VEGF expression was
      significantly down regulated by phosphorothioate oligodeoxynucleotide (PS-ODN)
      and VEGF RNAi transfection. However, VEGF RNAi transfection as well as VEGF and
      VEGFR2 neutralization antibody treatment did not decrease cell proliferation
      detected by MTT and CyQuant NF proliferation assay except that PS-ODN
      transfection caused a non-specific decrease on cell proliferation. VEGF RNAi
      transfection did not alter cell invasion, as demonstrated in a matrigel invasion
      assay. Matrix metalloproteinase-2 (MMP-2) and MMP-9, facilitating cell invasion
      and over expressed in glioma cells, were not altered by VEGF RNAi transfection,
      as shown by zymographic assays. Our data indicate that the decrease of endogenous
      VEGF expression may not affect glioma cell proliferation and invasion.

PMID- 17552363
TI  - Degenerate binding of tyrosinase peptides to MHC II Ad/Ed molecules.
AB  - Recently we defined the tyrosinase233-247IPYWDWRDAEKCDIC peptide as the
      pentadecamer sequence hosting the linear determinant of the anti-tyrosinase MAb
      T311. In order to understand the molecular features that render epitopic the
      amino acid tyrosinase233-247 sequence, we 1) analyzed the MHC II affinity of the
      tyrosinase233-247IPYWDWRDAEKCDIC peptide using RankPep as a binding prediction
      program, and 2) experimentally verified the actual peptide-MHC II interaction by
      carrying out peptide electrophoretic mobility shift assays. Nine random
      tyrosinase peptides were used as controls. Under the conditions used in this
      study, it was found that all of the ten tyrosinase peptides were capable of
      binding to Ad/Ed molecules in the gel-shift binding assay. Moreover, there was no
      correlation between the theoretical predicted Ad/Ed affinity and the experimental
      actual peptide binding. We conclude that Ad/Ed binding potential appears
      influential in the defining of tyrosinase233-247IPYWDWRDAEKCDIC peptide
      epitopicity.

PMID- 17552364
TI  - Anti-angiogenic effect of Biophytum sensitivum is exerted through its cytokine
      modulation activity and inhibitory activity against VEGF mRNA expression,
      endothelial cell migration and capillary tube formation.
AB  - Angiogenesis is a crucial step essential for the growth, progression and
      metastasis of solid tumors. Substances produced by inflammatory cells, such as
      cytokines play an important role in the stimulation and progression of
      angiogenesis. In this study we investigated the anti-angiogenic effect of
      Biophytum sensitivum, using in vivo as well as in vitro models. In vitro
      antiangiogenic activity was studied using B16-F10 melanoma cell-induced capillary
      formation in C57BL/6 mice. Intraperitoneal administration of the extract at a
      concentration of 50 mg/kg significantly inhibited the tumor directed capillary
      formation induced by melanoma cells. The cytokine profile in the serum of these
      animals showed a drastically increased level of proinflammatory cytokines such as
      IL-1beta, IL-6, TNF-alpha, GM-CSF and the direct endothelial cell proliferating
      agent, VEGF. Administration of Biophytum extract could differentially regulate
      these cytokine's elevation. The differential elevation is further evidenced by
      the increased production of IL-2 and tissue inhibitor of metalloprotease-1 (TIMP
      1) in the B16-F10 injected, extract treated animals. The extract of B. sensitivum
      at non-toxic concentrations (1 microg/ml, 5 microg/ml and 10 microg/ml) inhibited
      the VEGF-induced vessel sprouting in rat aortic ring assay. Moreover, B.
      sensitivum was able to inhibit the VEGF-induced proliferation, cell migration and
      capillary-like tube formation of primary cultured human endothelial cells.
      Furthermore B. sensitivum showed inhibitory effect on VEGF mRNA levels in B16-F10
      melanoma cells. Hence the observed antiangiogenic activity of the plant B.
      sensitivum is exerted through its cytokine modulation activity and inhibitory
      activity against VEGF mRNA expression.

PMID- 17552365
TI  - Feasible combination chemotherapy with nedaplatin and irinotecan for patients
      with non-small cell lung cancer and multiple high-risk factors.
AB  - We retrospectively analyzed the outcome of high-risk patients with non-small cell
      lung cancer (NSCLC) treated with nedaplatin (NP) and irinotecan (CPT) combination
      chemotherapy. Between July 2002 and January 2006, 31 NSCLC patients with multiple
      high-risk factors were treated with NP at 50 mg/m2 and CPT at 50 mg/m2 on days 1
      and 8 every 4 weeks. Among them, the patients had a total of 85 risk factors,
      including poor performance status (2 or 3) in 27, cardiac or pulmonary failure in
      15, symptomatic bone or brain metastasis in 9, and advanced age (> or = 75 years)
      in 8, as well as other factors. A total of 83 courses of the chemotherapy were
      administered and 24 patients were able to receive 2 to 4 courses. With regard to
      toxicities, 7 (8.4%) and 11 courses (13%) were associated with grade 4
      neutropenia and grade 3 febrile neutropenia, respectively. One patient suffered
      acute myocardial infarction. Each of the toxicities was controllable and there
      were no treatment-related deaths. One patient achieved CR, 13 achieved PR, 14 SD
      and 3 PD, and the overall response rate was 45.2%. Of 26 patients with stage IIIB
      or IV, the median survival time was 232 days, the 1-survival rate was 38.5%, and
      3 patients survived for more than 3 years. In conclusion, chemotherapy with NP
      and CPT appears to be safe and highly effective for high-risk patients with
      NSCLC.

PMID- 17552366
TI  - Expression of the prostate transglutaminase (TGase-4) in prostate cancer cells
      and its impact on the invasiveness of prostate cancer.
AB  - BACKGROUND: Prostate transglutaminase (TGase-4), has been identified as a TGase
      that has a pattern of prostate specific expression. This study sought to
      determine (i) the level of TGase-4 in human cancer cell lines including prostate
      cancer cells; (ii) to investigate the effect after knocking down the expression
      of TGase-4 transcript using a ribozyme transgene; (iii) to establish the effect
      of HGF/SF, a pro-invasion/metastasis cytokine, on the invasive capacity of TGase
      4 knockdown cells. METHODS: RT-PCR and quantitative RT-PCR were used to assess
      the presence of TGase-4 transcript at the mRNA level in a panel of 26 cell lines
      including 6 prostate cancer cell lines (PC-3, DU-145, CA-HPV-10, PZ-HPV-7, PNT2C2
      and PNT1A). A ribozyme transgene consisting of hammerhead ribozyme and antisense
      specific to TGase-4 was constructed using a pEF6 expression vector and
      transfected into CA-HPV-10 cell, a cell line highly expressed TGase-4. An in
      vitro invasion assay assessed the effects of HGF/SF on cell invasiveness.
      RESULTS: TGase-4 transcript was detected in a number of cell lines, including
      prostate, colorectal, lung and breast tumour cells. At the mRNA level, TGase-4
      was strongly expressed in CA-HPV-10 cells with lower levels of expression seen in
      PC-3, DU-145, PZ-HPV-7 and PNT1A cells. TGase-4 knock-down in CA-HPV-10 cells was
      established at the mRNA level. HGF/SF significantly increased the invasion of
      wild type (21.67 +/- 0.88; P < 0.001 vs. control 8.67 +/- 0.67) and control
      plasmid transfected cells (16.33 +/- 0.88; P < 0.001 vs. control 7.67 +/- 0.88)
      compared with untreated cells. However, cells transfected with the TGase-4
      ribozyme transgene had a reduced invasive capacity (9.33 +/- 0.88 P < 0.01 vs.
      control 4.33 +/- 0.88) through Matrigel. CONCLUSION: TGase-4 has a relatively
      wide profile of expression in human cancer cell lines and is strongly expressed
      in the low invasive CA-HPV-10 prostate cancer cell line. The molecule is
      associated with the invasive potential of prostate cancer cells.

PMID- 17552367
TI  - Sleep, development, and human health.

PMID- 17552368
TI  - Morphine-induced acetylcholine release at the hypoglossal motor nucleus:
      implications for opiate-induced respiratory suppression.

PMID- 17552369
TI  - Cyclic alternating pattern in the electroencephalogram: what is its clinical
      utility?

PMID- 17552370
TI  - A role for the molecular chaperone protein BiP/GRP78 in Drosophila sleep
      homeostasis.
AB  - STUDY OBJECTIVES: Microarray studies have identified numerous genes that change
      in response to prolonged wakefulness. The challenge is to determine which
      transcriptional changes translate into protein changes that are critical for
      recovery following sleep loss. BiP is a protein indicator of endoplasmic
      reticulum (ER) stress, and BiP mRNA increases in mouse and rat cerebral cortex
      and in Drosophila heads in response to sleep loss. We first sought to determine
      whether the expression of BiP protein parallels sleep homeostatic drive and
      dissipates with recovery sleep. We then sought to establish a key role for BiP in
      the homeostatic process of sleep by contrasting recovery sleep in models of over-
      and under-expression of BiP. SUBJECTS AND INTERVENTIONS: Drosophila melanogaster
      were used to take advantage of the UAS-Gal4 system to both over express wild-type
      BiP and express a dominant negative form of BiP. RESULTS: BiP protein rises two
      and a half fold across sleep loss and falls in recovery sleep, in parallel with
      gene changes. BiP over expression in the flies leads to an increase in recovery
      sleep in response to sleep loss, in parallel with a delay in the unfolded protein
      response. Flies with the dominant negative mutation and reduced functional BiP
      show the opposite effect. CONCLUSIONS: We show directly that BiP protein, a key
      indicator of ER stress is instrumental in determining the amount of recovery
      sleep following enforced wakefulness. We have thus identified a novel window into
      regulation of sleep homeostasis.

PMID- 17552371
TI  - Microdialysis delivery of morphine to the hypoglossal nucleus of Wistar rat
      increases hypoglossal acetylcholine release.
AB  - STUDY OBJECTIVES: The medullary hypoglossal nucleus (XII) innervates the
      genioglossal muscles of the tongue, and opioid-induced alterations in tongue
      muscle tone contribute to airway obstruction. Previous studies have shown that
      morphine causes a significant decrease in acetylcholine (ACh) release in some
      brain regions, but the effects of morphine on ACh release in XII have not been
      quantified. DESIGN: A within-subjects design was used to test the hypothesis that
      morphine alters ACh release in XII of anesthetized Wistar rat. ACh release during
      microdialysis with Ringer's solution (control) was compared to ACh release during
      dialysis delivery of opioids. SETTING: University of Michigan. PATIENTS OR
      PARTICIPANTS: N/A. INTERVENTIONS: Microdialysis delivery of opioids to XII.
      MEASUREMENTS AND RESULTS: Morphine caused a statistically significant,
      concentration-dependent increase in XII ACh release. The increase in XII ACh
      release caused by 10 microM morphine was blocked by the mu opioid antagonist
      naloxone and not blocked by the kappa opioid antagonist norbinaltorphimine.
      CONCLUSIONS: The data comprise the first direct measures of ACh release in XII
      and support the conclusion that morphine depresses hypoglossal nerve activity, in
      part, by increasing ACh release in XII. Activation of mu opioid receptors on
      inhibitory neurons within XII likely disinhibits cholinergic terminals, causing
      increased ACh release. The results are consistent with previous studies showing
      that blocking the enzymatic degradation of ACh in XII significantly inhibited
      tongue muscle activity.

PMID- 17552372
TI  - Randomized clinical effectiveness trial of nurse-administered small-group
      cognitive behavior therapy for persistent insomnia in general practice.
AB  - STUDY OBJECTIVES: Persistent insomnia, although very common in general practice,
      often proves problematic to manage. This study investigates the clinical
      effectiveness and the feasibility of applying cognitive behavior therapy (CBT)
      methods for insomnia in primary care. DESIGN: Pragmatic randomized controlled
      trial of CBT versus treatment as usual. SETTING: General medical practice.
      PARTICIPANTS: Two hundred one adults (mean age, 54 years) randomly assigned to
      receive CBT (n = 107; 72 women) or treatment as usual (n = 94; 65 women).
      INTERVENTION: CBT comprised 5 sessions delivered in small groups by primary care
      nurses. Treatment as usual comprised usual care from general practitioners.
      MEASUREMENTS AND RESULTS: Assessments were completed at baseline, after
      treatment, and at 6-month follow-up visits. Sleep outcomes were appraised by
      sleep diary, actigraphy, and clinical endpoint. CBT was associated with
      improvements in self-reported sleep latency, wakefulness after sleep onset, and
      sleep efficiency. Improvements were partly sustained at follow-up. Effect sizes
      were moderate for the index variable of sleep efficiency. Participants receiving
      treatment as usual did not improve. Actigraphically estimated sleep improved
      modestly after CBT, relative to no change in treatment as usual. CBT was also
      associated with significant positive changes in mental health and
      energy/vitality. Comorbid physical and mental health difficulties did not impair
      sleep improvement following CBT. CONCLUSION: This study suggests that trained and
      supervised nurses can effectively deliver CBT for insomnia in routine general
      medical practice. Treatment response to small-group service delivery was
      encouraging, although effect sizes were smaller than those obtained in efficacy
      studies. Further research is required to consider the possibility that CBT could
      become the treatment of first choice for persistent insomnia in primary
      healthcare.

PMID- 17552373
TI  - ERP evidence of enhanced excitatory and reduced inhibitory processes of auditory
      stimuli during sleep in patients with primary insomnia.
AB  - STUDY OBJECTIVES: Increased information processing around the onset of sleep and
      during sleep has been suggested as an important factor for the pathogenesis of
      insomnia. The purpose of the present study was to examine the processing of
      auditory information during sleep in patients with insomnia through the recording
      of event-related potentials (ERPs). DESIGN: A mixed design was used in which
      subject group was a between-subject factor and sleep stage and type of tone
      presented were within-subject factors. PARTICIPANTS: Fifteen patients with
      primary insomnia and 15 normal sleepers (controls) were studied. MEASUREMENTS AND
      RESULTS: An odd-ball paradigm was conducted to evoke ERPs throughout the night.
      Patients with insomnia showed larger N1 and smaller P2 to rare tones, smaller
      N350 to standard tones, and slower P900 to both tones during the first 5 minutes
      of continuous stage 2 sleep. No consistent ERP differences were detected between
      the 2 groups when the waveforms were averaged across the whole night.
      CONCLUSIONS: Patients with insomnia showed an enhancement in attention and a
      reduction in the inhibitory process that normally facilitates sleep onset in the
      beginning part of sleep. The results partially support the hyperarousal theory,
      ie, enhanced information processing during the initiation of sleep is a
      contributing factor for insomnia.

PMID- 17552374
TI  - The selective extrasynaptic GABAA agonist, gaboxadol, improves traditional
      hypnotic efficacy measures and enhances slow wave activity in a model of
      transient insomnia.
AB  - STUDY OBJECTIVES: Evaluate the hypnotic efficacy of gaboxadol, a selective
      extrasynaptic GABAA agonist (SEGA), in a phase advance model of transient
      insomnia. DESIGN: A randomized, double-blind, cross-over study in which habitual
      sleep time was advanced by 4 h. SETTING: Sleep research laboratories.
      PARTICIPANTS: 109 healthy subjects (18-58 y). INTERVENTIONS: Gaboxadol 5 mg, 10
      mg, and 15 mg (GBX5, GBX10, GBX15) versus placebo (PBO). Zolpidem 10 mg (ZOL10)
      was used as an active reference. MEASUREMENTS: Polysomnographic (PSG) and self
      reported (s) sleep measures RESULTS: Wakefulness after sleep onset (WASO)
      decreased (P < 0.05) and total sleep time (TST) increased (P < 0.001) in all
      treatments versus PBO. Latency to persistent sleep was shorter (P < 0.05) than
      PBO for all treatments except GBX5. GBX10 and GBX15 increased slow wave activity
      (SWA; 0.75-4.5 Hz, P < 0.001) and theta activity (4.75-7.75Hz; P < 0.001) and
      reduced sigma activity (12.25-15.0 Hz; significant for GBX15 only, P < 0.001)
      compared to PBO in NREM sleep EEG, in a dose-response manner. Zolpidem suppressed
      power density over a broad low frequency range including delta and theta
      frequencies (2.25-8.0 Hz, P < 0.05) and also enhanced sigma activity (P < 0.001).
      Self-reported sWASO and sTST improved for all treatments versus PBO (P < 0.05).
      Self-reported sleep latency was reduced following GBX10 (P < 0.05) and ZOL10 (P <
      0.001). Neither drug treatment was associated with residual effects the morning
      after treatment. CONCLUSIONS: Gaboxadol and zolpidem improved objective and
      subjective efficacy measures in this model of transient insomnia. The gaboxadol
      induced enhancement of SWA and theta activity and the reduction of sigma activity
      contrasts with zolpidem's effects on the spectral EEG. These differences may
      reflect the different mechanisms of action of the two drugs.

PMID- 17552375
TI  - Sleep deprivation elevates expectation of gains and attenuates response to losses
      following risky decisions.
AB  - STUDY OBJECTIVES: Using a gambling task, we investigated how 24 hours of sleep
      deprivation modulates the neural response to the making of risky decisions with
      potentially loss-bearing outcomes. DESIGN: Two experiments involving sleep
      deprived subjects were performed. In the first, neural responses to decision
      making and reward outcome were evaluated. A second control experiment evaluated
      responses to reward outcome only. PARTICIPANTS: Healthy right-handed adults
      participated in these experiments (26 [mean age 21.3 years] in Experiment 1 and
      13 [mean age 21.7 years] in Experiment 2.) MEASUREMENTS AND RESULTS: Following
      sleep deprivation, choices involving higher relative risk elicited greater
      activation in the right nucleus accumbens, signifying an elevated expectation of
      the higher reward once the riskier choice was made. Concurrently, activation for
      losses in the insular and orbitofrontal cortices was reduced, denoting a
      diminished response to losses. This latter finding of reduced insular activation
      to losses was also true when volunteers were merely shown the results of the
      computer's decision, that is, without having to make their own choice.
      CONCLUSIONS: These results suggest that sleep deprivation poses a dual threat to
      competent decision making by modulating activation in nucleus accumbens and
      insula, brain regions associated with risky decision making and emotional
      processing.

PMID- 17552376
TI  - Slow eye movements and subjective estimates of sleepiness predict EEG power
      changes during sleep deprivation.
AB  - RATIONALE: The aim of the present study was to assess, intraindividually, the
      relationship among slow eye movements, electroencephalogram (EEG) power, and
      subjective measures of sleepiness during a 40-hour sleep deprivation comparing 2
      experimental conditions: eyes-open and eyes-closed. METHODS: Nineteen normal
      subjects participated in a sleep-deprivation protocol with recordings of the
      waking Cz-A1-2 EEG in 36 sessions at 1-hour intervals starting at 10:00 AM. Each
      session consisted of a 2-minute eyes-closed period, followed by a 4-minute eyes
      open period. Electrooculogram, self-ratings (Karolinska Sleepiness Scale and
      Visual Analog Scale for Global Vigor), and tympanic temperature were also
      recorded. RESULTS: Changes in sleepiness and alertness are paralleled by
      increases in slow eye movements and theta and delta EEG power. The beginning of
      the rise of delta, theta, and slow eye movement activity corresponded to the
      nadir of temperature, peaking at 7:00AM. Cross-correlational analyses showed that
      changes in slow eye movements were strictly phase locked to those in slow
      frequency EEG bands and in subjective measures. The comparison of time intervals
      that were equivalent with respect to circadian phase confirms the effects of the
      increased sleepiness on slow eye movement activity and on the other measures. The
      temporal concordance of the different physiologic and subjective measures is also
      reflected in the individual time courses. Individual and group analyses converged
      in indicating that slow eye movements can be considered reliable indexes of
      sleepiness but only in the eyes-closed condition. CONCLUSIONS: Results suggest
      that subjective and EEG changes associated with higher sleepiness are paralleled
      by an increase in slow eye movement activity, but this relationship exists almost
      exclusively with the eyes closed. Hence, its use in practical and operational
      contexts seems limited.

PMID- 17552377
TI  - Prevalence and risk factors of subjective sleepiness in the general adult
      population.
AB  - STUDY OBJECTIVES: The aim of this study was to investigate the prevalence and
      risk factors of self-reported excessive daytime sleepiness (EDS) in Norway.
      DESIGN: The Epworth Sleepiness Scale was administered by a telephone interview to
      a random sample of 2301 adult inhabitants of Norway. Questions of demography,
      symptoms of sleep disorders, and depression were included. SETTING: Norway.
      PARTICIPANTS: Two thousand three hundred one subjects, 18 years and older.
      INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: The mean score of the Epworth
      Sleepiness Scale was 6.95 (SD = 3.8), and 17.7% had a score (> 10), indicating
      EDS. Univariate logistic regression analyses showed that being a man; living in
      southern Norway; working nights; being young; having symptoms of cataplexy,
      restless legs, or periodic limb movement in sleep; having breathing pauses in
      sleep; and having symptoms of depression were significantly related to EDS. Of
      these 9 predictors, only symptoms of restless legs did not maintain the
      significant relationship with EDS when a multiple logistic regression analysis
      was performed. CONCLUSIONS: The prevalence of EDS was high in this adult
      Norwegian population sample. EDS seems to be related to several symptoms of sleep
      disorders.

PMID- 17552378
TI  - The case of "Judge Nodd" and other sleeping judges--media, society, and judicial
      sleepiness.
AB  - STUDY OBJECTIVES: Review cases of judicial sleepiness and subsequent outcomes,
      including media and community attitudes. DESIGN: Index case report and Internet
      search in English language at 2 recent time points. PARTICIPANTS: Index case and
      14 other cases of judicial sleepiness reported on the Internet. MEASUREMENTS:
      Qualitative review of media and Internet reports. RESULTS: The index and other
      cases highlighted the role of the media seeking a punitive approach to
      occupational sleepiness, similar to that observed within the transport sector. In
      the index case, the judge's driver's license was withdrawn, despite official
      acknowledgement of effective treatment of sleep apnea. In 10 cases, judicial
      sleepiness resulted in a retrial and, in up to 5 cases, resulted in dismissal or
      retirement of the judge. In most cases, the cause of sleepiness was not
      determinable. CONCLUSION: Judicial sleepiness is not uncommon and is viewed
      negatively by the media, community, and judicial system. Active monitoring of the
      judiciary for sleepiness and sleep disorders is suggested.

PMID- 17552379
TI  - Increased adherence to CPAP with a group cognitive behavioral treatment
      intervention: a randomized trial.
AB  - STUDY OBJECTIVE: To improve adherence to continuous positive airway pressure
      (CPAP) treatment in participants with obstructive sleep apnea (OSA) using a
      cognitive behavioral therapy (CBT) intervention. DESIGN: A randomized controlled
      trial. SETTING: A major teaching hospital in Sydney (2005). PARTICIPANTS: One
      hundred individuals (96 men), ranging in age from 32 to 81 years, diagnosed with
      OSA. INTERVENTION: Two 1-hour CBT interventions (including a video of real CPAP
      users) plus treatment as usual (mask fitting and information) or treatment as
      usual only. MEASUREMENTS AND RESULTS: Hours of CPAP usage was assessed at 7
      nights and 28 nights. Adherence was defined as usage at least 4 hours per night.
      Questionnaires measuring self-efficacy, social support, and expectancy (mediators
      of adherence) were given after intervention or after usual treatment. A higher
      adherence to CPAP therapy was found in the CBT group (2.9 hours difference)
      relative to treatment as usual (P < 0.001) at 28 days. Only 4 participants in the
      CBT group did not initiate treatments after their titration study, compared with
      15 in the treatment as usual group (P < 0.02). The CBT group had significantly
      higher scores for self-efficacy (P < 0.001) and social support P < 0.008) but not
      for expectancy. CONCLUSIONS: The CBT intervention resulted in both increased
      adherence and "uptake" of CPAP and therefore would be expected to reduce the
      social, economic, and health-related consequences of untreated OSA.

PMID- 17552380
TI  - The cyclic alternating pattern demonstrates increased sleep instability and
      correlates with fatigue and sleepiness in adults with upper airway resistance
      syndrome.
AB  - OBJECTIVE: To clarify the relationship between sleep instability and subjective
      complaints in patients with upper airway resistance syndrome (UARS). METHODS:
      Thirty subjects (15 women) with UARS and 30 age- and sex-matched controls in a
      prospective, single-blind, case-control study. Blinded cyclic alternating pattern
      (CAP) electroencephalogram analysis and scales of fatigue and sleepiness were
      completed. ANALYSIS: Mann-Whitney U tests for independent, nonparametric
      variables between groups and chi2 tests for nonparametric variables with defined
      standard values. RESULTS: Patients with UARS had significantly more complaints of
      fatigue and sleepiness, compared with controls, demonstrated on their Fatigue
      Severity Scale (P < 0.001) and Epworth Sleepiness Scale (P < 0.001). By design,
      the mean apnea-hypopnea index was normal in both groups, whereas the respiratory
      disturbance index was greater in patients with UARS than in those without (14.5
      +/- 3.0 vs 9 +/- 5.2, respectively [P < 0.001]). CAP analysis demonstrated
      abnormal non-rapid eye movement sleep with abnormally increased CAP rate,
      electroencephalogram arousals, A2 index, and A3 index. Decreased A1 index in
      controls was consistent with their more normal progression of sleep. CAP rate
      correlated with both the Epworth Sleepiness Scale (r = 0.38, P < 0.01) and the
      Fatigue Severity Scale (r = 0.51, P < 0.0001), and there was a positive trend
      between the Fatigue Severity Scale and phase A2 index (r = 0.29, P < 0.05).
      CONCLUSION: Compared with age- and sex-matched controls, patients with UARS have
      higher electroencephalogram arousal indexes and important non-rapid eye movement
      sleep disturbances that correlate with subjective symptoms of sleepiness and
      fatigue. These disturbances are identifiable with sensitive measures such as CAP
      analysis but not with traditional diagnostic scoring systems.

PMID- 17552381
TI  - The effects of adaptive servo ventilation on cerebral vascular reactivity in
      patients with congestive heart failure and sleep-disordered breathing.
AB  - STUDY OBJECTIVE: Hypercapnic cerebral vascular reactivity (HCVR) is reduced in
      patients with congestive heart failure (CHF) and sleep-disordered breathing
      (SDB); this may be associated with an increased risk of stroke. We tested the
      hypothesis that reversal of SDB in CHF patients using adaptive servo ventilation
      (ASV) would increase morning HCVR. DESIGN: Interventional, cross-over clinical
      study. SETTING: Research sleep laboratory. PATIENTS: Ten CHF patients with SDB,
      predominantly obstructive sleep apnea. INTERVENTIONS: The HCVR was measured from
      the change in middle cerebral artery velocity, using pulsed Doppler ultrasound.
      HCVR was determined during the evening (before) and morning (after) 1 night of
      sleep on ASV and 1 night of spontaneous sleep (control). MEASUREMENTS AND
      RESULTS: Compared with the control situation, ASV decreased the apnea-hypopnea
      index (group mean +/- SEM, control: 48 +/- 12, ASV: 4 +/- 1 events per hour).
      HCVR was 23% lower in the morning, compared with the evening, on the control
      night (evening: 1.3 +/- 0.2, morning: 1.0 +/- 0.2 cm/sec per mm Hg, P < 0.05) and
      27% lower following the ASV night (evening: 1.5 +/- 0.2, morning: 1.1 +/- 0.2
      cm/sec per mm Hg, P < 0.05). The effect of ASV on the evening-to-morning
      reduction in HCVR was not significant, compared with the control night (0.02
      cm/sec per mm Hg, 95% confidence interval: -0.28, 0.32 P = 0.89). CONCLUSIONS: In
      CHF patients with SDB, HCVR was reduced in the morning compared with the evening.
      However, removal of SDB for 1 night did not reverse the reduced HCVR. The
      relatively low morning HCVR could be linked with an increased risk of stroke.

PMID- 17552382
TI  - The impact of a 4-hour sleep delay on slow wave activity in twins discordant for
      chronic fatigue syndrome.
AB  - OBJECTIVES: Chronic fatigue syndrome (CFS) has been associated with altered
      amounts of slow wave sleep, which could reflect reduced delta
      electroencephalograph (EEG) activity and impaired sleep regulation. To evaluate
      this hypothesis, we examined the response to a sleep regulatory challenge in CFS.
      DESIGN: The first of 3 consecutive nights of study served as laboratory
      adaptation. Baseline sleep was assessed on the second night. On the third night,
      bedtime was delayed by 4 hours, followed by recovery sleep. Total available sleep
      time was held constant on all nights. SETTING: A research sleep laboratory.
      PARTICIPANTS: 13 pairs of monozygotic twins discordant for CFS. INTERVENTIONS:
      N/A. MEASUREMENTS AND RESULTS: Power spectral analysis quantified slow wave
      activity (SWA) in the 0.5-3.9 Hz band in successive NREM periods (stage 2, 3, or
      4) on each night. To ensure comparability, analyses were restricted to the first
      4 NREM periods on each night. Data were coded for NREM period and twin pair.
      Repeated-measures analysis of variance (ANOVA) contrasted sleep delay effects
      across NREM periods between twin pairs. A second ANOVA calculated the SWA in each
      NREM period in recovery sleep relative to baseline SWA. The 2 groups of twins
      were similar on baseline SWA power. After sleep delay, CFS twins exhibited
      significantly less SWA power in the first NREM period of recovery sleep and
      accumulated a smaller percentage of SWA in the first NREM period than their co
      twins. CONCLUSIONS: CFS is associated with a blunted SWA response to sleep
      challenge, suggesting that the basic sleep drive and homeostatic response are
      impaired.

PMID- 17552383
TI  - Selective laser trabeculoplasty in phakic and pseudophakic eyes.
AB  - BACKGROUND AND OBJECTIVE: To evaluate the effect of pseudophakia on the success
      of selective laser trabeculoplasty in lowering intraocular pressure (IOP).
      PATIENTS AND METHODS: In this retrospective, nonrandomized clinical trial, a
      chart review of all patients who underwent selective laser trabeculoplasty from
      September 2002 to June 2004 using a frequency-doubled Q-switched 532-nm Nd:YAG
      laser was performed. Changes in IOP and statistical significance were determined
      at each follow-up period. Average decrease in IOP and success rates for phakic
      and pseudophakic eyes were compared statistically at each time period. RESULTS:
      In the phakic group, mean IOP decreased from 18.1 to 15.5 mm Hg (P < .0005) and
      mean glaucoma medication use decreased from 2.1 to 1.6 medications after 24
      months of follow-up. In the pseudophakic group, mean IOP decreased from 18.3 to
      15.2 mm Hg (P < .005) and mean glaucoma medication use decreased from 2.2 to 1.6
      medications. Success rates ranged from 54% to 67% in the phakic group and 52% to
      65% in the pseudophakic group. No statistically significant difference between
      phakic and pseudophakic eyes in decreased IOP or success rates was seen at any
      time point (P > .05). No significant complications occurred in either group.
      CONCLUSIONS: Selective laser trabeculoplasty is effective in lowering IOP in both
      phakic and pseudophakic patients.

PMID- 17552384
TI  - Closed funnel-shaped proliferative vitreoretinopathy in patients with cognitive
      disabilities.
AB  - BACKGROUND AND OBJECTIVE: To report severe proliferative vitreoretinopathy (PVR)
      cases in patients with cognitive disabilities treated with vitrectomy. PATIENTS
      AND METHODS: This retrospective study included 10 eyes of 9 consecutively
      enrolled patients with cognitive disabilities. The severity of PVR was grade C
      type 2345 with widespread preretinal and subretinal proliferation in all cases.
      The surgical management was vitrectomy with scleral buckling, retinotomy, removal
      of preretinal and subretinal proliferation, and silicone oil tamponade. Mandatory
      prone positioning and limb restraint were not indicated. Postoperative anatomic
      and functional success were studied. The follow-up ranged from 3 to 62 months
      (mean: 25.8 months). RESULTS: The retina was attached in 10 eyes (100%) at the
      final examination. Functional success, based on an improvement in patient daily
      activity, was achieved in 4 patients (44%). No severe complications were noted.
      CONCLUSIONS: Treatment with vitrectomy was effective to manage severe PVR in
      patients with cognitive disabilities and contributed to improve daily life.

PMID- 17552385
TI  - Adjustable suture surgery for correction of various types of strabismus.
AB  - BACKGROUND AND OBJECTIVE: This study was conducted to analyze the efficacy of the
      adjustable suture technique for correction of strabismus in patients with
      different types of strabismus. PATIENTS AND METHODS: This was an observational
      case series of patients who underwent the adjustable suture technique for
      correction of strabismus. A total of 33 adult patients (16 males and 17 females)
      with a minimum postoperative follow-up period of 6 months were included in the
      study. Patients were analyzed in three groups (patients with exotropia,
      esotropia, and vertical deviations). Success criteria determined were percentage
      change in the angle of deviation for far and near fixation, need for reoperation,
      and relief of diplopia. RESULTS: The median percentage change in the angle of
      deviation for far and near fixation was 86.60% and 84%, 92.50% and 94.44%, and
      100% and 100% in the exotropia, esotropia, and vertical deviation groups,
      respectively. There was no need for reoperation, and postoperative adjustment
      performed 24 hours after surgery was needed in 30.3% of patients due to diplopia.
      CONCLUSIONS: The adjustable suture technique seems to be an effective method in
      the correction of various types of strabismus.

PMID- 17552386
TI  - Preemptive sub-Tenon's anesthesia for pars plana vitrectomy under general
      anesthesia: is it effective?
AB  - BACKGROUND AND OBJECTIVES: To determine whether irrigation of the sub-Tenon's
      space with anesthetic agents during pars plana vitrectomy (PPV) involving general
      anesthesia decreases postoperative pain, analgesic use, or nausea. PATIENTS AND
      METHODS: A prospective, controlled trial of 46 consecutive patients requesting
      general anesthesia for PPV who were randomized to receive or not receive a sub
      Tenon's space injection prior to surgery. A mixture of 3 mL of 2% lidocaine with
      hyaluronidase and 3 mL of 0.5% bupivacaine was used to induce local blockade.
      Pain, postoperative nausea, and analgesia use were evaluated. RESULTS: Local
      blockade did not significantly alter the proportion of reported pain at 30
      minutes and 2, 4, and 24 hours after the operation. The local blockade had no
      effect on reducing postoperative nausea or the number of patients requiring pain
      medication. CONCLUSIONS: Local blockade prior to surgery in patients undergoing
      PPV under general anesthesia does not significantly decrease postoperative pain,
      analgesic use, or nausea.

PMID- 17552387
TI  - Comparison of ultrasonic energy expenditures and corneal endothelial cell density
      reductions during modulated and non-modulated phacoemulsification.
AB  - BACKGROUND AND OBJECTIVE: To compare the Legacy 20000 Advantec continuous and
      Infiniti hyperpulse modes (Alcon Laboratories, Fort Worth, TX) with respect to
      average power, machine-measured phacoemulsification time, total stopwatch real
      time spent within the phacoemulsification process, balanced salt solution (BSS)
      volume, and corneal endothelial cell density losses. PATIENTS AND METHODS: A
      background study was done of consecutive patients operated on with the Legacy (n
      = 60) and Infiniti (n = 40) machines programmed with identical parameters and
      using the continuous mode only. A primary study of another set of consecutive
      cases was operated on using the Legacy (n = 87) and Infiniti (n = 94) with the
      same parameters, but using the hyperpulse mode during quadrant removal with the
      Infiniti. Measurements for each set included average power and
      phacoemulsification time with corneal endothelial cell densities, BSS volume, and
      time spent in the phacoemulsification process. RESULTS: Similarities were found
      in the background study for average power percent and average minutes of
      phacoemulsification time. In the primary study, similarities were found for total
      minutes in the phacoemulsification process, BSS usage, and ECD losses, and
      differences were found for average power percent (P< .001) and machine-measured
      phacoemulsification minutes (P< .001). CONCLUSIONS: The Legacy and Infiniti
      performed similarly in continuous mode. With the Infiniti hyperpulse mode, a
      total ultrasonic energy reduction of 66% was noted. The machines required the
      same amount of total stopwatch measured time to accomplish phacoemulsification
      and produced the same 5% corneal endothelial cell loss. Therefore, clinically,
      these two machines behave in a comparable manner relative to safety and
      effectiveness.

PMID- 17552388
TI  - The relationship between retrobulbar and choroidal hemodynamics in non
      neovascular age-related macular degeneration.
AB  - BACKGROUND AND OBJECTIVE: To evaluate the relationship between retrobulbar and
      choroidal hemodynamics in non-neovascular age-related macular degeneration.
      PATIENTS AND METHODS: Thirteen patients with age-related macular degeneration
      were assessed by both color Doppler imaging and scanning laser ophthalmoscope
      indocyanine green (ICG) angiography. Color Doppler imaging was used to measure
      peak systolic and end diastolic velocity (from which the resistance index, a
      measure of the resistance to flow downstream, was calculated) in the retrobulbar
      vessels. Scanning laser ophthalmoscope ICG angiograms were analyzed by area
      dilution analysis for quantitative choroidal fluorescence intensity assessment.
      Color Doppler imaging parameters were correlated with scanning laser
      ophthalmoscope ICG area dilution analysis parameters. RESULTS: A good correlation
      was found between the posterior ciliary arteries resistance index and scanning
      laser ophthalmoscope ICG area dilution analysis fluorescence duration.
      CONCLUSIONS: Scanning laser ophthalmoscope ICG area dilution analysis "duration"
      may serve as an alternative to color Doppler imaging in assessing the resistance
      to blood flow in the posterior ciliary arteries.

PMID- 17552389
TI  - Extrafoveal choroidal neovascularization secondary to wet age-related macular
      degeneration treated with intravitreal bevacizumab.
AB  - Considering the risk of recurrence of extrafoveal or juxtafoveal lesions after
      thermal laser treatment and the risk of poor response to photodynamic therapy, it
      seems reasonable to discuss with the patient the risks and benefits of
      antiangiogenic therapy. A case of age-related macular degeneration with an
      extrafoveal choroidal neovascularization treated with a single injection of
      intravitreal bevacizumab is described. The patient showed both anatomic and
      visual acuity improvement at 1 month following treatment that persisted even at
      the 8-month follow-up visit. Further studies are needed to validate the real risk
      benefit ratio of intravitreal bevacizumab for extrafoveal exudative lesions
      versus the current treatments available.

PMID- 17552390
TI  - Intravitreal triamcinolone acetonide injection in CRVO associated with Wegener's
      granulomatosis.
AB  - A 33-year-old man developed unilateral non-ischemic central retinal vein
      occlusion associated with systemic Wegener's granulomatosis. Four milligrams of
      triamcinolone acetonide was injected intravitreally twice 6 months apart in
      conjunction with ongoing systemic immunosuppressive therapy. No change was made
      in the systemic immunosuppressive regimen. Wegener's granulomatosis should be
      considered in the differential diagnosis of central retinal vein occlusion in the
      young age group and intravitreal triamcinolone acetonide is a good adjunct to
      systemic immunosuppressive therapy that eliminates the need for modifying the
      systemic treatment regimen.

PMID- 17552391
TI  - Intravitreal bevacizumab in aggressive posterior retinopathy of prematurity.
AB  - The anatomic response to intravitreal bevacizumab injection in three patients
      with aggressive, posterior retinopathy of prematurity is described. In all cases,
      the worse eye was treated with a single intravitreal injection of 0.75 mg of
      bevacizumab as monotherapy or complementary to laser therapy. In 24 hours, all
      injected eyes showed regression of the tunica vasculosa lentis and iris vessel
      engorgement and disappearance of iris rigidity. In addition, plus disease and
      retinal proliferation began to regress. None of the eyes required additional
      treatment. Follow-up of up to 10 months

PMID- 17552392
TI  - Epiretinal deposit of triamcinolone acetonide at the posterior pole after
      intravitreal injection.
AB  - The authors investigated possible toxic side effects of epiretinal triamcinolone
      acetonide deposits at the posterior pole after an intravitreal injection in both
      a vitrectomized and a non-vitrectomized eye. The vitrectomized eye developed
      massive epiretinal triamcinolone acetonide deposits at the posterior pole that
      were less pronounced in the non-vitrectomized eye. After resolution of the
      deposits, no morphologic signs of retinal toxicity were apparent. Mild scattered
      visual field defects did not correlate with the localization of the triamcinolone
      acetonide deposits. However, because recent in vitro studies indicate potential
      cytotoxicity, patients should be instructed to keep their heads in an upright
      position after intravitreal triamcinolone acetonide injection to avoid deposits
      at the posterior pole.

PMID- 17552393
TI  - Retinal detachment due to a retinal break in the macular atrophy of a myopic
      choroidal neovascularization.
AB  - In a case of rhegmatogenous retinal detachment in a highly myopic eye, repeated
      optical coherence tomography revealed a small break around the scar tissue of a
      myopic choroidal neovascularization that was difficult to observe with
      conventional slit-lamp examination using a contact lens due to severe
      chorioretinal atrophy. This article presents the optical coherence tomography
      findings of the retinal detachment before and after the treatment and discusses
      the pathologic role of myopic choroidal neovascularization in the retinal
      detachment.

PMID- 17552394
TI  - Pheochromocytoma presenting with bithalamic infarction, dementia, and increased
      intraocular pressure.
AB  - The authors describe a case of pheochromocytoma presenting with bithalamic
      infarction, dementia, and elevated intraocular pressure. The patient received
      glaucoma treatment to suppress high intraocular pressure in addition to
      antihypertensive and antidiabetic medication for his complaints. Bilateral fundus
      examination and visual field defects revealed glaucoma-like changes.
      Adrenelectomy improved all complaints and all medications were stopped.
      Intraocular pressure and visual field changes improved. Pheochromocytoma
      presenting with bithalamic infarction, dementia, and increased IOP in the same
      patient is unusual. Adrenelectomy can improve dementia, increased IOP, and
      glaucoma-like changes in such cases.

PMID- 17552395
TI  - Chronic angle-closure glaucoma secondary to a suprachoroidal effusion induced by
      central retinal vein occlusion.
AB  - A 68-year-old woman presented to the ophthalmology emergency clinic with a
      painful left eye of a few hours' duration. One month prior, the patient had
      presented with a central retinal vein occlusion in the same eye. Examination
      revealed an intraocular pressure of 32 mm Hg in the left eye with 360 degree
      angle closure unaltered by indentation, a patent iridectomy from a previous
      combined phacoemulsification and trabeculectomy surgery, and no evident iris or
      angle neovascularization. Ultrasound biomicroscopic examination revealed a large
      suprachoroidal effusion with anterior rotation of the ciliary body and secondary
      angle closure in the left eye. The patient underwent successful pars plana
      vitrectomy, radial optic neurotomy, intra-vitreal triamcinolone acetonide
      injection, and goniosynechialysis.

PMID- 17552396
TI  - Serial multifocal visual Evoked potential recordings in compressive optic
      neuropathy.
AB  - This article compares the results of serial multifocal visual evoked potential
      (mfVEP) recordings with the results of static automated perimetry obtained during
      a period of 21 months from a patient with a unilateral compressive optic nerve
      lesion (meningioma). Monocular and interocular mfVEP analyses were performed and
      compared with normal control subjects. The number of sectors deviating from
      normal at a significance level of less than .01 in the monocular mfVEP plots
      appeared to correlate best with the mean deviation of the visual fields. In this
      patient with compressive optic neuropathy, mfVEP provided additional objective
      data for evaluating visual function over time.

PMID- 17552397
TI  - A new technique to mark the donor and host corneas in keratoplasty.
AB  - A new technique is described to easily and accurately mark the donor and the host
      cornea in keratoplasty using simple, readily available instruments and utilizing
      a simple mathematical equation. This technique will allow for even distribution
      of the donor tissue in the recipient bed.

PMID- 17552398
TI  - Use of triamcinolone acetonide particles to visualize aqueous outflow.
AB  - Using triamcinolone acetonide suspension within the anterior chamber allows
      visualization of fluid outflow for glaucoma surgeries where aqueous egress from
      the eye is desired for pressure control. Dilute non-preserved triamcinolone
      acetonide particles can be injected into the anterior chamber at the end of
      intraocular surgeries to assess fluid outflow and to provide an anti-inflammatory
      effect at the end-target tissue.

PMID- 17552399
TI  - Documentation of optic nerve pit with macular schisis-like cavity by spectral
      domain OCT.
AB  - The authors report using spectral domain optical coherence tomography (OCT) to
      observe a patient with an optic nerve pit and macular schisis-like spaces. An 8
      microm axial resolution prototype spectral domain OCT and stereo fundus
      photography were used to observe the patient. A macular schisis-like cavity was
      present at baseline and additional cystic changes developed in the nerve fiber
      layer over a period of 16 months; however, the visual acuity remained stable at
      20/20. Spectral domain OCT provides greater detail of the changes in morphology
      and structure of macular schisis and edema associated with an optic nerve pit.

PMID- 17552400
TI  - Effect of amelogenin extracellular matrix protein and compression on hard-to-heal
      venous leg ulcers.
AB  - OBJECTIVE: To compare hard-to-heal venous leg ulcers treated with compression
      therapy alone versus compression therapy with amelogenin protein. Parameters used
      were: percentage reduction in wound size, number of improved ulcers, pain related
      to the disease and at dressing changes, amount and nature of exudate, and the
      safety and tolerability of the two treatments. METHOD: This was an open
      randomised comparative parallel group multicentre investigation with a three-week
      run-in period. Inclusion criteria included adult, mobile patients with hard-to
      heal venous leg ulcers that had been treated with compression therapy for at
      least one month prior to screening. The ulcers had to be at least six months old,
      with a surface area at inclusion of 10-30cm2, and not demonstrating excessive
      exudate or signs of infection. At the end of the run-in period, additional
      criteria for eligibility, such as change in wound area of +/- > or = 50% and a
      wound area between 8cm2 and 36cm2 were applied. Patients were randomised to
      treatment with amelogenin plus high compression bandaging or high compression
      bandaging alone. All participants received high compression bandaging therapy one
      month prior to and during the three-week run-in period, as well as throughout the
      12 weeks of active treatment. RESULTS: Eighty-three patients were randomised and
      received treatment: 42 with high compression plus amelogenin (amelogenin group)
      and 41 to high compression therapy alone (control group). The amelogenin group
      had a greater percentage reduction in ulcer size (mean - 33.1%) compared with the
      control group (mean - 11.07%) from baseline to the last visit (p = 0.06). The
      number of improved ulcers was significantly greater (p = 0.01) in the amelogenin
      group than in the control group. Compensating for baseline characteristics by
      multiple regression resulted in a statistically significant (p = 0.03) larger
      reduction in change in ulcer size in the amelogenin group. Statistically
      significant differences in favour of the amelogenin group were also found for
      reduction in ulcer-related pain (p = 0.01), reduction in pain at dressing changes
      (p = 0.02) and the proportion of patients with 'none' or 'low' levels of exudate
      (p = 0.01). CONCLUSION: The combination of amelogenin with high compression
      promotes the healing process in hard-to-heal ulcers. Application of amelogenin as
      an adjunct to compression results in a significant reduction in ulcer size,
      improvement in the state of ulcers, reduced pain and a larger proportion of
      ulcers with low levels of exudate. The results of this study are statistically
      and clinically significant.

PMID- 17552401
TI  - Rapid healing of a late diagnosed sickle cell leg ulcer using a new combination
      of treatment methods.

PMID- 17552402
TI  - Evaluation of the dissemination and implementation of a nutritional guideline for
      pressure ulcer care.
AB  - OBJECTIVE: In 2004 the European Pressure Ulcer Advisory Panel nutritional working
      group developed a nutritional guideline for pressure ulcer prevention and
      treatment. This study investigated the degree to which the guideline was
      disseminated and implemented in clinical practice. METHOD: A cross-sectional
      study was undertaken in health-care organisations in The Netherlands, Germany and
      the UK. A printed, standardised questionnaire which followed Rogers' model of the
      innovation-decision process was developed, translated and distributed to 1087
      health-care organisations. RESULTS: The response rate was 33% (n = 363). Sixty
      one per cent of respondents knew of the guideline. Twenty-five per cent had
      applied it to their clinical practice and used it for nutritional screening. The
      main barrier to the provision of nutritional support appeared to be lack of
      knowledge and skills. CONCLUSION: One year after its dissemination, more than
      half of respondents knew of the guideline, with one in four applying it to their
      practice. The guideline was better disseminated and implemented in The
      Netherlands and UK than in Germany, where only 4% of participants had used it.

PMID- 17552403
TI  - A lively conference with plenty of debate for the NPUAP in Texas.

PMID- 17552404
TI  - A new initiative aiming to improve our understanding of shear force.

PMID- 17552405
TI  - Does VAC increase the risk of venous thromboembolism?

PMID- 17552406
TI  - A study of the factors influencing how frequently district nurses re-apply
      compression bandaging.
AB  - OBJECTIVE: This UK study aimed to identify the factors district nurses use in
      deciding how frequently to re-apply compression bandaging. METHOD: Qualitative
      observational data from district nurses' visits to patients and subsequent team
      meetings were used to structure in-depth interviews with nurses. Data were
      analysed according to the principles of grounded theory. RESULTS: Ten factors
      emerged as influences on the frequency of re-application. These included
      knowledge of leg ulcer care, recognition of the symptoms of wound deterioration,
      confidence, time management, patient preferences and sources of information.
      CONCLUSION: The influences reported and observed are likely to be of use in
      designing future bandaging trials and in the delivery of leg ulcer education. The
      research identifies links between frequency of bandaging and resource awareness,
      clinical expertise, patient preference and research evidence. Decision-makers
      could be taught to organise large numbers of factors into several smaller
      categories that might result in more accurate decision-making regarding the
      frequency of re-bandaging.

PMID- 17552407
TI  - Fulminant infection of the lower limb in a diabetic patient.

PMID- 17552408
TI  - Use of topical corticosteroids on chronic leg ulcers.
AB  - OBJECTIVE: Topical corticosteroids are widely used in the management of chronic
      wounds, yet there is little evidence to support this. This pilot study aimed to
      identify current practice by three specialist nurses and to assess the efficacy
      of topical corticosteroids. METHOD: Data on healing, pain relief, exudate
      reduction and control of hypergranulation tissue were collected on 34 patients
      whose wounds were treated with topical corticosteroids prospectively in three
      centres over a three-month period. RESULTS: Twenty-seven patients (79%) benefited
      from the application of topical corticosteroid either in terms of healing, pain
      relief, exudate reduction or the control of hypergranulation tissue. Two wounds
      deteriorated and treatment was immediately withdrawn. CONCLUSION: Suppression of
      inflammation plays an important role in healing and pain relief. Applying topical
      corticosteroids to the wound can accelerate healing and reduce pain in certain
      cases. However, careful monitoring is essential as there is a risk of
      sensitisation with prolonged use as well as a potential increased risk of
      infection.

PMID- 17552409
TI  - Dermacyn on the infected foot ulcers of 10 patients.

PMID- 17552410
TI  - Use of a nanocrystalline silver dressing on lymphatic ulcers in patients with
      chronic lymphoedema.
AB  - OBJECTIVE: A prospective evaluation to explore the effect of treating patients
      with chronic lower limb lymphoedema and lymphatic ulcers using a nanocrystalline
      dressing and multilayer bandaging. METHOD: Ulcers were cleansed and dressed with
      a nanocrystalline silver dressing, an alginate dressing and a hydrocellular
      dressing, followed by multilayer short-stretch compression bandages. A digital
      planimetry system was used to calculate the ulcer surface area. In cases of
      multiple ulcers, the areas were added together. RESULTS: Eight patients with
      chronic lower limb lymphoedema plus ulcers were included. Median age was 53.7
      years (range 39.2-72.3). Mean ulcer size was 10.5cm2 (range: 0.8-33.8). All
      ulcers completely healed after one to nine weeks of treatment. CONCLUSION: This
      protocol has been effective in healing lymphatic ulcers and was well accepted by
      patients. There were no adverse effects or withdrawals. Further studies with
      larger numbers of patients are required to support these results.

PMID- 17552411
TI  - [Tumors in the gallbladder: a possible differentiation between malignant and
      benign tumours].
AB  - In a 59-year-old woman with pain in the right upper abdomen, echography and CT
      scan revealed adenomatosis of the gallbladder. Her symptoms did not disappear
      after cholecystectomy, even though echography showed no further abnormality. In a
      46-year-old man with fever and weight loss, echography revealed two polyps in the
      gallbladder. Following cholecystectomy, histopathology revealed cholesterol
      polyps and an infection with Entamoeba coli. In a 63-year-old man with systemic
      symptoms, a biopsy of the echographically diagnosed tumour of the gallbladder
      revealed that he had actually had cholecystitis. The management was wait-and-see
      and the patient recovered completely. In a 68-year-old woman with jaundice and
      attacks of abdominal pain, a CT-scan revealed gallstones. The symptoms recurred
      following an ERCP. Following cholecystectomy, an adenocarcinoma of the
      gallbladder was found. One year later, a contact metastasis developed forwhich
      she received radiotherapy. After 4 years she was in good condition. Patients with
      a tumour in the gallbladder are often diagnosed with gallbladder cancer, which
      has a poor prognosis. Other diseases should also be considered, since the
      treatment and prognosis differ greatly. It is important to differentiate at an
      early stage. Ultrasound, CT and MRI have improved the possibility of
      differentiating and choosing the correct treatment.

PMID- 17552412
TI  - [Population screening for urinary protein loss: a sensible action].
AB  - In 2006, the Dutch Nierstichting (Kidney Foundation) provided people with urinary
      dipsticks to determine whether they suffered from urinary protein loss. It was
      suspected that 0.5% of adult inhabitants would have hidden renal disease. Within
      two weeks, more than one million people had applied to receive the dipsticks.
      They were advised to contact their general practitioner if they tested positive.
      Blockade of the renin-angiotensin-aldosterone system (RAAS) in subjects with
      known renal disease and proteinuria improves renal and cardiac survival. However,
      many patients currently develop end-stage renal disease without prior knowledge
      ofhaving chronic kidney disease. These patients can be detected by screening for
      proteinuria or albuminuria. Japanese studies showed that about 5% of the general
      population have positive dipstick tests. It is to be expected that about 1% will
      be truly macroalbuminuric and another 2-3% will be microalbuminuric.
      Macroalbuminuria is the consequence of manifest glomerular damage, while
      microalbuminuria is in most cases related to underlying diabetes or hypertension
      (which frequently are not yet diagnosed). In both conditions, treatment with RAAS
      blockade is indicated and is aimed at both cardiac and renal protection. There
      are arguments indicating that screening of the general population for urinary
      protein loss is cost-effective.

PMID- 17552413
TI  - [Intelligence and the explanation for socio-economic inequalities in health].
AB  - Attention is increasingly being paid to the role of cognitive ability to explain
      socio-economic inequalities in health. The universal socio-economic gradient in
      health, where each rung lower on the socio-economic ladder implies worse health,
      has still not been satisfactorily explained scientifically. Because cognitive
      ability is related to a multitude of social outcomes in a similarly graded
      manner, hypothesising that cognitive ability plays a major role in health
      inequalities by socio-economic status is appealing. Recent empirical studies have
      shown that at least part of socio-economic health inequalities can indeed be
      explained by differences in cognitive ability. However, this does not imply that
      we should be pessimistic about future attempts to break the chain that links
      socio-economic status and cognitive ability with health. During some life stages,
      environmental factors may be able to influence cognitive ability. Interventions
      may therefore be targeted in order to optimize these effects. In addition, there
      is evidence that cognitive ability is correlated with health-related behaviours
      such as smoking, excessive alcohol consumption and obesity. Therefore, another
      opportunity for reducing health inequalities related to cognitive ability and
      socio-economic status would be to develop tailored interventions to improve
      health-related behaviours in disadvantaged groups. However, the first priority is
      to further investigate the role of cognitive ability in health inequalities by
      examining various health outcomes, different age groups and variations across the
      life course.

PMID- 17552414
TI  - [Cardiovascular and gastrointestinal risks associated with selective and non
      selective NSAIDs].
AB  - There has been much discussion regarding the cardiovascular and gastrointestinal
      safety of traditional and COX-2 selective NSAIDs. The national and international
      guidelines differ in their recommendations. Selective COX-2 inhibitors seem to
      have a diminished risk for severe gastrointestinal complications in the short
      term, but the long-term benefit has not yet been proven. In various studies, COX
      2 selective NSAIDs have been associated with an increased risk of cardiovascular
      complications. This connection has been clearly demonstrated only for rofecoxib.
      Celecoxib seems to lead to an increased risk only at high dosages. However, more
      patients will have to be followed for a longer period to confirm these results.
      There is insufficient evidence that the COX-2 selective agents lead to more
      frequent cardiovascular complications than the traditional NSAIDs. In patients
      with an increased risk of gastrointestinal complications and no cardiovascular
      risk, there is no preference for either COX-2 selective NSAIDs or the combination
      of traditional NSAIDs and a proton pump inhibitor. If dyspepsia develops during
      the use of a traditional NSAID, then it seems more effective to add a proton-pump
      inhibitor to the traditional NSAID rather than replacing it by a COX-2 selective
      NSAID.

PMID- 17552415
TI  - [Guideline 'Cardiovascular Risk Management'].
AB  - The aim of the clinical practice guideline 'Cardiovascular risk management' is an
      integral approach to all relevant risk factors for cardiovascular disease (CVD)
      caused by atherothrombosis. Patients with CVD, diabetes mellitus type 2 (DM2),
      elevated blood pressure or cholesterol, men of 50 years or older who smoke and
      women of 55 years or older who smoke are eligible for assessment of relevant risk
      factors for CVD. All high-risk patients should receive lifestyle counselling. In
      patients with CVD the use of acetylsalicylic acid and often, depending on the
      specific disease, a beta-blocker or an angiotensin converting enzyme (ACE)
      inhibitor are recommended. The use of a statin is recommended if the LDL
      cholesterol concentration is > or = 2.5 mmol/l. In patients with DM2, the use of
      statins is recommended if LDL-cholesterol is > or = 2.5 mmol/l and use of a blood
      pressure lowering drug with a systolic blood pressure > or = 140 mmHg, as well as
      glucose lowering drugs. In patients without CVD and DM2, the need for drug
      treatment will be determined by estimation of the absolute 10-year mortality risk
      of CVD. Treatment is recommended if this risk exceeds 10%. The treatment and
      follow-up plan will be determined individually, depending on the risk profile,
      morbidity, comorbidity and patient's preferences.

PMID- 17552416
TI  - [Diagnostic image (323). An infant with a tumour on a finger].
AB  - A 7-month-old girl was presented with a tumour on the lateral side of the
      terminal phalanx of the right digitus IV, which displayed the histopathological
      characteristics ofa digital fibroma.

PMID- 17552417
TI  - [Intelligence, socio-economic status and hospital admissions of young adults].
AB  - OBJECTIVE: To determine whether socio-economic differences in hospital admissions
      of adolescents and young adults are related to differences in intelligence.
      DESIGN: . Retrospective cohort study. METHODS: The data were derived from a group
      of 10,231 young adults and adolescents who were followed for a total of 47,212
      person years with regard to their hospital admissions. Intelligence was measured
      in the first year of secondary school by 2 non-verbal intelligence tests for
      fluid intelligence. Data from hospital admissions were matched to a large-scale
      educational and occupational cohort. Data were analysed with Cox proportional
      hazards analysis. RESULTS: Intelligence was not found to be related to hospital
      admissions. However, a low occupational and educational level of the young adults
      or their parents, was strongly related to heightened risk for hospital
      admissions. In particular, the low socio-economic status of a respondent was
      associated with heightened risk for hospital admissions due to accidents
      (relative risk: 3.49; 95% confidence interval: 1.91-6.39). CONCLUSION: The small
      extent to which the socio-economic differences in hospital admissions seem to be
      based upon fluid intelligence, at least in adolescents and young adults, as well
      as the heightened risks of hospital admissions in lower socio-economic status
      groups and the associated high costs for health care legitimise further study of
      the determinants of these differences.

PMID- 17552418
TI  - [Diversity of complaints in manifesting carcinoma of the gallbladder].
AB  - A man of 47 years with hypercholesterolaemia had no complaints but the family
      doctor suspected cholecystolithiasis because of abnormal results of the
      haematological study. Ultrasonography of the abdomen revealed a polyp in the
      gallbladder. The patient underwent laparoscopic cholecystectomy. Pathological
      examination revealed that the polyp was a carcinoma. No evidence for a recurrence
      was found during a return visit after 2 years. A woman of 74 years was admitted
      to the hospital due to persistent rectal bleeding. She had fever, loss of
      appetite, nausea and weight loss. A bleeding duodenal ulcer was identified during
      gastroduodenoscopy. Laparotomy was performed due to haemodynamic instability.
      During the operation an abnormal gallbladder was found with infiltration in and
      perforation of the duodenum. The gallbladder was resected and the perforation of
      the duodenum was sutured. Pathological examination revealed carcinoma of the
      gallbladder. A palliative policy was adhered to; the patient died 1 month later.
      Carcinoma ofthe gallbladder is an uncommon but highly fatal malignancy. Several
      risk factors have been identified and treatment is primarily surgical.

PMID- 17552419
TI  - [Subglottal stenosis as the first symptom of Wegener's granulomatosis].
AB  - A 51-year-old woman presented with a sore throat, hoarseness and difficulty in
      swallowing. On physical examination she was found to have stridor. Laryngoscopy
      revealed a subglottal stenosis. Infection was thought to be the cause but this
      was not confirmed by sputum or laryngeal cultures. Because of the clinical course
      and the presence of antineutrophil cytoplasmic proteinase-3 antibodies, Wegener's
      granulomatosis was diagnosed. Immunosuppressive therapy led to improvement. At 4
      year follow-up the patient had scleritis but no ENT problems. Wegener's
      granulomatosis should always be considered in a patient with a subglottal
      stenosis; it can be the first symptom of this disease.

PMID- 17552421
TI  - [New scientific arguments for further reducing the use of tobacco, also in the
      hotel, restaurant and catering business].

PMID- 17552422
TI  - [The pharmacological prevention and treatment of diabetes mellitus; significance
      of 2 recent, large studies for the use of rosiglitazone].

PMID- 17552423
TI  - [Indications for respiratory complications during the use of oral nifedipine as a
      tocolytic agent, especially in patients with multiple pregnancies].

PMID- 17552424
TI  - [Isolated orchidodynia as the initial symptom of aneurysm of the abdominal
      aorta].

PMID- 17552425
TI  - [No increase in medical consumption in general practice after induced abortion].

PMID- 17552426
TI  - [No increase in medical consumption in general practice after induced abortion].

PMID- 17552427
TI  - [Multifactorial influences on age-related macular degeneration].
AB  - Age-related macular degeneration (AMD) is the most common cause of vision loss in
      the elderly population of the western world. Identification and perfect knowledge
      of the risk factors is of particular importance not only for the understanding of
      the disorder, but also for the treatment and the prevention of the disease.
      Recent advances in the identification of its genetic and environmental components
      are reviewed.

PMID- 17552428
TI  - [Macular pigment and age-related macular degeneration. Clinical implications].
AB  - The potential impact of macular pigment on the development of age-related macular
      degeneration (AMD) is currently a major research avenue. The role of oxidative
      damage in the pathogenesis of AMD has been recently confirmed by the results of a
      large randomized clinical trial, the AREDS (Age-Related Eye Disease Study). This
      study has established that high-dose supplementation with vitamins C and E, beta
      carotene, and zinc might prevent AMD progression and visual acuity loss in a
      large but determined subset of patients. Macular pigment components (mainly
      lutein and zeaxanthin) are highly resistant to free radicals. Moreover, extensive
      data from clinical, epidemiological and experimental studies suggest that lutein
      and zeaxanthin might protect against the development of AMD. Furthermore, an
      additional intake of lutein and/or zeaxanthin seems to induce an increase of the
      density of the macular pigment. However, a careful review of the available data
      suggest that only future randomized clinical trials will allow to determine the
      exact role of lutein and zeaxanthin in the prevention of AMD.

PMID- 17552429
TI  - [Some notions about possible harmlessness and/or toxicity of the antioxidant
      micronutriments].
AB  - Report # 8 of the Age Related Eye Disease Study (AREDS) showed the interest of a
      cocktail of antioxidant micronutrients for the uni- or bilateral intermediate
      forms and the unilateral evolved forms of Age related Macular Degeneration. This
      use of supranutritional amounts aiming at obtaining a therapeutic effect
      corresponds to the concept of "neutraceuticals" which can be opposed to the
      concept of nutritional amounts. Although the AREDS was carried out under strict
      conditions, the evolution of knowledge in micronutrition since its design has led
      to some criticism of both the amounts of the micronutrients and the composition
      of the formulation. For example several authors pointed out that beta-carotene
      used at 3 fold the daily recommendations could have harmful effects, especially
      among smokers or former smokers. Other authors pointed out that vitamin E, at
      amounts corresponding to 40 to 60 fold the amounts recommended could be
      correlated with a lethal risk. We develop here some notions about safety and/or
      harmlessness of the antioxidant micronutrients.

PMID- 17552430
TI  - [Vitamins for prevention of age related macular degeneration: efficacy and risk].
AB  - Nutritional theories have been greatly strengthened by the results of the AREDS
      study, showing efficiency of high doses of beta-carotene, vitamin C and E, and
      Zinc to prevent severe forms of age-related macular degeneration (AMD). Despite
      an excellent tolerance of these high doses, some concerns have been expressed
      about potential side-effects of non nutritional doses. For example, high doses of
      beta carotene should not be given to smokers because they could activate the
      occurrence of a lung cancer. Many ophthalmologists replace beta carotene by
      lutein and zeaxanthin, while efficiency of this association has not been proven.
      The AREDS study raises many questions but stimulates the research into the
      prevention of AMD. Future studies should include polyunsaturated fatty acids and
      lutein and zeaxanthin supplementations as they seem to be among the most
      promising preventive therapies in AMD.

PMID- 17552431
TI  - [The source of antioxidants].
AB  - Free radicals are thought to play an important part in the phenomenon of aging,
      especially as regards the eye. Antioxydants represent an interesting means of
      limiting the damage due to oxydation, as is shown by a number of studies. Food is
      an unexpected source of antioxydants, which exist in the form of thousands of
      different compounds. Colored fruits and vegetables are known to be rich in
      carotenoids, some of which such as lutein and zeaxanthin tend to accumulate at
      the level of the macula. But there are plenty of other foodstuffs that supply the
      antiradical armoury, as has been shown by analytical findings over a number of
      years. Legumes and whole cereals have a very high antioxydant potential. Other
      items, from tea to...chocolate, contribute to providing antioxydants through
      food. Although some specific antioxydants appear so far to be particularly
      interesting, the results gathered over a number of years in various fields show
      the advantages of combining several interacting antioxydants. A diet with a
      strong vegetal component, without being vegetarian, provides a very broad range
      of antioxydants and thus appears to be an important defense against oxidative
      stress.

PMID- 17552432
TI  - [Legislation and risk potential of harmful use of complementary nutrition
      supplements].
AB  - Ophthalmologists have to deal with the prescription of commercial preparations
      containing essential nutrients and/or phytonutrients with antioxidant or other
      properties that are presented as able to protect the eyes against several
      degenerative diseases. This kind of preparation has to be in conformity with the
      Belgian Legislation on food and food products that mentions the nature and the
      quantity of active components they are allowed to contain. Nevertheless, they
      cannot mention allegations related to health or to the treatment of diseases.
      Carotenoids such as lutein, zeaxanthin or lycopene are not covered by this
      Legislation as they are not pro-vitamin A. Therefore, they have to be considered
      as potentially harmful according to the Belgian Legislation dated March 3, 1992.
      Finally, their long-term toxicity has never been documented and no dietary
      recommendations exist as far as they are concerned. On the contrary, several
      warnings have been published about their chronic intake at supranutritional
      doses. Even if a complementary administration of these carotenoids is in some way
      meaningful, it is a pity that their commercial use has preceded the scientific
      data that remain necessary to collect about them. It seems preferable to advise
      "dietary" alternatives and avoid the use of unbalanced food complements.

PMID- 17552433
TI  - Iatrogenic ocular vascular occlusions: case reports.
AB  - Report of two patients with severe loss of visual acuity after surgery in the
      head and neck area. Ophthalmic examination and imaging studies demonstrate an
      occlusion of the ophthalmic and central retinal arteries. In both cases, the
      underlying physiopathology is the embolisation by an intra-operatively injected
      substance. Embolisation is thought to occur via anastomosing branches between the
      external and internal carotid arteries. These cases demonstrate that surgery in
      head and neck area can result in unexpected and devastating ocular complications.

PMID- 17552434
TI  - Miliary tuberculosis and bilateral multifocal choroidal involvement: place of
      indocyanine green angiography.
AB  - PURPOSE: To present the clinical features and angiographic findings of choroidal
      involvement in two cases with miliary tuberculosis. METHODS: 49-year and 23-year
      old men were hospitalized for fever of unknown origin and they received a
      diagnosis of miliary tuberculosis following the systemic work-up. Both cases
      experienced mild visual acuity disturbances prior to initiation of systemic
      treatment. They underwent full ophthalmological examination including fluorescein
      and indocyanine green angiography. RESULTS: The visual acuity of first case was
      20/30 in OD, and 20/25 in OS. There was trace of cells in the anterior chamber
      and mild vitritis OU. Visual acuity of the second case was 20/20 OU. Anterior
      segment was unremarkable OU. Ophthalmoscopy of both cases showed cream-colored
      patchy choroidal infiltrations especially located at the posterior pole OU.
      Fluorescein and indocyanine green angiographies were obtained with Heidelberg
      scanning laser ophthalmoscope. These lesions were hypofluorescent in early phases
      of fluorescein angiography and demonstrated gradually increased hyperfluorescence
      in late phases. Same lesions were hypofluorescent throughout the indocyanine
      green angiography and well delineated. Both patients received a systemic
      treatment of isoniazid, rifampicin, ethambutol and morphazinamide. Most of the
      choroidal lesions resolved without apparent changes whereas some healed as
      chorioretinal scars. CONCLUSION: In patients with miliary tuberculosis,
      indocyanine green angiography seems to show choroidal involvement much better
      than the fluorescein angiography and may be a more important diagnostic tool than
      fluorescein angiography during the disease course.

PMID- 17552435
TI  - Late-onset capsular bag distention syndrome after cataract surgery: 2 case
      reports.
AB  - Late capsular bag distension syndrome occurs most of the time with the
      accumulation of opaque milky fluid behind the IOL, without refractive change,
      like in one of our cases. The other case that we will describe had an
      accumulation of a clear fluid behind the IOL with an induced hyperopia. To the
      best of our knowledge, this is the first published report of capsular bag
      distension syndrome with a shift towards hyperopia. In both case the visual
      acuity and the initial refraction was restored after Nd:YAG posterior
      capsulotomy.

PMID- 17552436
TI  - [Characteristics of retinal detachment following neodymium YAG laser posterior
      capsulotomy: clinical and therapeutic aspects].
AB  - PURPOSE: To study the clinical characteristics and the therapeutic results of
      retinal detachment following neodymium YAG laser posterior capsulotomy. MATERIAL
      AND METHODS: A retrospective study of 28 patients (28 eyes) operated in
      department B of the Hedi Rais Institute of Ophthalmology (Tunis, Tunisia) between
      march 1993 and january 2005 for retinal detachment following neodymium YAG laser
      posterior capsulotomy. We study the preoperative clinical characteristics of the
      retinal detachment and the anatomic and functionnal results. RESULTS: The mean
      age of the patients is 53.4 years. Fourteen patients are men and eleven have high
      myopia. Ten patients are aphakic and eighteen pseudophakic. The retinal
      detachment is total or subtotal in 19 eyes (67.9%). The macula is detached in 27
      cases (96.4%). The retinal tears are posterior in 9 cases (paravascular retinal
      break or macular hole) and peripheral in fifteen cases. In 4 cases no tear is
      found. Vitreoretinal proliferation is advanced in 10 cases. Eleven patients
      underwent episcleral surgery and 17 endocular surgery. The final success rate is
      89%. The postoperative visual acuity increases in 20 cases. It is superior to
      1/10 in 14 cases. The minimum follow-up is 6 months. CONCLUSION: The retinal
      detachment after neodymium laser posterior capsulotomy is serious due to severe
      vitreoretinal proliferation wich influences the anatomic results.

PMID- 17552437
TI  - Re: Vestibular, vaginal and urethral relations in spayed dogs with and without
      lower urinary tract signs.

PMID- 17552438
TI  - Science, medicine, academia, and the future of the ACVIM.

PMID- 17552439
TI  - Cyclooxygenase (COX) inhibitors and the intestine.
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs) have long been used for the
      treatment of pain and inflammation because of their inhibitory effects on
      cyclooxygenase (COX). For almost as long as NSAIDs have been in use, multiple
      adverse effects have been noted. Assessment of many of these adverse effects have
      been complicated because of the discovery of multiple splice variants of the cox
      gene, and a greater array of COX inhibitors, especially the COX-2 selective
      inhibitors have become available. Some of these adverse effects cannot be readily
      explained by the effect of these drugs on COX. This has sparked a new field of
      investigation into the COX-independent effects of the COX inhibitors. The major
      noncyclooxygenase targets of the COX inhibitors of particular relevance to
      inflammation and the gastrointestinal tract are phosphatidylinositol 3'-kinase
      Akt signaling, uncoupling of oxidative phosphorylation, PPARgamma, nuclear factor
      KB, mitogen activated protein kinases, and heat shock proteins.

PMID- 17552440
TI  - Anticoagulant effects of low-molecular-weight heparins in healthy cats.
AB  - BACKGROUND: Low-molecular-weight heparin (LMWH) has potential benefit in cats at
      risk for thromboembolic disease. However, LMWH pharmacokinetics has not been
      characterized in the cat. Drug effect with LMWH may be evaluated with analysis of
      factor Xa inhibition (anti-Xa) or thromboelastography (TEG). HYPOTHESIS:
      Administration of LMWH at previously recommended dosages and schedules to healthy
      cats will result in inhibition of factor Xa and hypocoagulable TEG. ANIMALS: In
      vivo research with heparin was performed in 5 purpose-bred cats. METHODS: In a
      prospective study with randomized crossover design, heparin or placebo was
      administered. Treatments were unfractionated heparin (UFH), 250 IU/kg q6h;
      dalteparin, 100 IU/kg q12h; enoxaparin, 1 mg/kg q12h; or 0.9% saline, 0.25 mL/kg
      q6h. Each drug was administered for 5 consecutive days followed by a minimum
      washout of 14 days. Baseline and post-treatment analyses included anti-Xa, TEG,
      and prothrombin time/activated partial thromboplastin time. RESULTS: Mean anti-Xa
      activity 4 hours after enoxaparin (0.48 U/mL) approached the human therapeutic
      target (0.5-1.0 U/mL); however, mean trough anti-Xa activity was below detection
      limits. Mean anti-Xa activity 4 hours after dalteparin was lower, and only 1 cat
      attained therapeutic target at a single time point. Cats receiving UFH attained
      target anti-Xa activity and changes in TEG at trough and 4 hours. CONCLUSIONS:
      Cats have rapid absorption and elimination kinetics with LMWH therapy. On the
      basis of pharmacokinetic modeling, cats will require higher dosages and more
      frequent administration of LMWH to achieve human therapeutic anti-factor Xa
      activity of 0.5-1 U/mL. Peak anti-Xa activity is predicted at 2 hours after
      administration of LMWH.

PMID- 17552441
TI  - Urinary catecholamine and metanephrine to creatinine ratios in healthy dogs at
      home and in a hospital environment and in 2 dogs with pheochromocytoma.
AB  - BACKGROUND: Measurement of high concentrations of urine catecholamines and
      metanephrines is useful in diagnosing pheochromocytoma in humans. Stress
      increases catecholamine excretion in urine. HYPOTHESIS: Stress of a hospital
      visit increases urinary catecholamine and metanephrine excretion in dogs.
      ANIMALS: Fourteen clinically normal dogs, 2 dogs with pheochromocytoma. METHODS:
      Voided urine samples were collected by the owners 7 days before (t-7), during the
      hospital visit immediately after diagnostic procedures (t0), as well as 1 (t1)
      and 7 days (t7) after the hospital visit. Urine catecholamine and metanephrine
      concentrations were measured using high-pressure liquid chromatography and
      expressed as ratios to urine creatinine concentration. RESULTS: In client-owned
      dogs epinephrine and norepinephrine ratios at t0 were significantly higher
      compared with ratios at t7. Metanephrine and normetanephrine ratios at t-7, t0,
      and t1 did not differ significantly from each other; however, at t7 they were
      significantly lower compared to values at t-7. In staff-owned dogs no significant
      differences were detected among the different collecting time points for any
      variable. Metanephrine and normetanephrine ratios were significantly higher in
      client-owned dogs compared to staff-owned dogs at t-7, t0, and t1 but not at t7.
      CONCLUSIONS AND CLINICAL IMPORTANCE: Stress associated with a hospital visit and
      with the sampling procedure causes increases in urine catecholamine and
      metanephrine excretion. Urine collection for the diagnosis of pheochromocytoma
      probably should take place at home after adaptation to the sampling procedure.

PMID- 17552442
TI  - Genetic cause of autosomal recessive hereditary nephropathy in the English Cocker
      Spaniel.
AB  - BACKGROUND: Autosomal recessive hereditary nephropathy (ARHN) in the English
      Cocker Spaniel is caused by a type IV collagen defect, but the underlying
      mutation is unknown. ANIMALS: One hundred thirty-four English Cocker Spaniels (12
      with ARHN, 8 obligate carriers, and 114 others), 3 mixed breed dogs with X-linked
      hereditary nephropathy (XLHN), and 7 other dogs without hereditary nephropathy
      were included. METHODS: Diagnosis of ARHN was based on transmission electron
      microscopy and immunostaining of kidney. Quantitative real time reverse
      transcriptase polymerase chain reaction (qRT-PCR) was used to compare COL4A3,
      COL4A4, and COL4A5 mRNA concentrations in the renal cortex from ARHN-affected
      English Cocker Spaniels, XLHN-affected dogs, and dogs without hereditary
      nephropathy. The entire coding region of COL4A4 was sequenced in 2 ARHN-affected
      dogs, 2 obligate carriers, 2 English Cocker Spaniels of unknown status, and 2
      healthy mixed breed dogs. The exon containing the mutation was sequenced for all
      134 English Cocker Spaniels. RESULTS: Quantitative real time RT-PCR implicated
      COL4A4 as the gene harboring the mutation, and sequencing identified a single
      nucleotide substitution at base 115 as the cause of ARHN in English Cocker
      Spaniels. This mutation, which causes a premature stop codon in exon 3 of COL4A4,
      was segregated with clinical status in all affected dogs and obligate carriers.
      The mutation also was identified in 39 of 114 other English Cocker Spaniels with
      previously unknown status. CONCLUSIONS AND CLINICAL IMPORTANCE: The cause of this
      disease has been identified, and use of a test for the mutation will permit
      eradication of ARHN in the English Cocker Spaniel.

PMID- 17552443
TI  - Effect of control of systolic blood pressure on survival in cats with systemic
      hypertension.
AB  - BACKGROUND: Systemic hypertension is a common clinical problem, often occurring
      in association with renal disease in cats. Limited information is available to
      assess the effect of blood pressure and the treatment of hypertension on
      survival. HYPOTHESIS: That adequacy of blood pressure control is associated with
      the duration of survival in cats with systolic hypertension. ANIMALS: One hundred
      and forty-one client-owned cats with systolic hypertension. METHODS: Hypertensive
      cats were treated with amlodipine besylate and were followed until death or the
      study end point. Time-averaged systolic blood pressure (SBPOT) after
      implementation of antihypertensive medication and stabilization of systolic blood
      pressure (SBP) was calculated by using the equation (area under the
      curve/survival [days]). Cats were divided into quartiles based on their SBPOT,
      representing varying levels of blood pressure control (median [25th, 75th
      percentile]: Q1 = 137 [132, 141] mm Hg, Q2 = 148 [145, 151] mm Hg, Q3 = 157 [155,
      158] mm Hg, Q4 = 170 [164, 175] mm Hg). Survival and clinical variables were
      compared between the quartiles. Cox proportional hazard regression analysis was
      used to determine the association of age, renal function, proteinuria, SBPOT, and
      the presence of hyperthyroidism on survival. Urine protein to creatinine ratio
      (UP:C) was compared at diagnosis of hypertension and after initiating treatment.
      RESULTS: Only UP:C and SBP at diagnosis differed significantly between SBPOT
      quartiles. Proteinuria was the only variable significantly related to survival in
      hypertensive cats. A significant decline in UP:C was found in cats treated with
      amlodipine besylate. CONCLUSIONS AND CLINICAL IMPORTANCE: Proteinuria before and
      after treatment of hypertension is strongly associated with survival in cats with
      systolic hypertension. Treatment with amlodipine besylate can result in a
      significant reduction in UP: C.

PMID- 17552444
TI  - Evaluation of client-specific outcome measures and activity monitoring to measure
      pain relief in cats with osteoarthritis.
AB  - BACKGROUND: There are no validated systems for measuring pain from osteoarthritis
      in cats. HYPOTHESIS: Owner subjective assessments and an activity monitor (AM)
      can be used to detect pain in cats with osteoarthritis and to assess efficacy of
      treatments. ANIMALS: Thirteen cats older than 10 years old, with owner-assessed
      decreases in activity, painful arthritic joints, and clinically normal blood work
      were included and evaluated for 3 weeks. METHODS: A collar-mounted AM measured
      activity and a client-specific outcome measure (CSOM) questionnaire characterized
      the severity of impairment. Overall global quality of life was also evaluated for
      each treatment. In weeks 2 and 3, meloxicam (0.1 mg/kg, day 1; 0.05 mg/kg, days 2
      5) or a placebo was administered in a blinded, randomized, cross-over manner to
      test the assessment systems. RESULTS: The cats had a median of 4 arthritic
      appendicular joints. Activity counts for the week when cats (complete data on
      activity; n=9) were administered meloxicam were significantly higher than at
      baseline (P = .02) but not after placebo (P = .06). Baseline activity counts were
      not significantly different from placebo (P = .6). The CSOM data (n=13) showed
      that owners considered their cats to be more active on meloxicam compared with
      baseline (P = .001) and placebo (P < .004), and more active on placebo than at
      baseline (P < .01). Global quality of life improved significantly with meloxicam
      (P < .042). CONCLUSIONS AND CLINICAL IMPORTANCE: Both an AM and a CSOM system can
      detect behavior associated with pain relief in cats that are arthritic. Objective
      activity data might allow subjective assessment systems to be validated for use
      in clinical studies.

PMID- 17552446
TI  - Day-to-Day variation of the urine protein: creatinine ratio in female dogs with
      stable glomerular proteinuria caused by X-linked hereditary nephropathy.
AB  - BACKGROUND: Interpretation of serial urine protein:creatinine (UPC) values is
      confounded by a lack of data regarding random biologic variation of UPC values in
      dogs with stable glomerular proteinuria. HYPOTHESIS: That there is minimal day-to
      day variability in the UPC of dogs with unchanging proteinuria and the number of
      measurements needed to reliably estimate UPC varies with the magnitude of
      proteinuria. ANIMALS: Forty-eight heterozygous (carrier) female dogs with X
      linked hereditary nephropathy (XLHN) causing stable proteinuria. METHODS: Urine
      samples were obtained daily by cystocentesis for 3 consecutive days on 183
      occasions (549 samples). The UPC was measured for each sample with a single dry
      film chemistry auto-analyzer. Data were analyzed retrospectively by a power of
      the mean model because the variance of UPC values within the 3-day evaluation
      periods increased as the magnitude of proteinuria increased. RESULTS: To
      demonstrate a significant difference (P < .05) between serial values in these
      proteinuric dogs, the UPC must change by at least 35% at high UPC values (near
      12) and 80% at low UPC values (near 0.5). One measurement is adequate to reliably
      estimate the UPC when UPC <4, but 2-5 determinations are necessary at higher UPC
      values. CONCLUSIONS AND CLINICAL IMPORTANCE: These guidelines for interpretation
      of serial UPC values in female dogs with XLHN may also be helpful for
      interpretation of UPC values in dogs with other glomerulopathies.

PMID- 17552445
TI  - Bacterial culture results from liver, gallbladder, or bile in 248 dogs and cats
      evaluated for hepatobiliary disease: 1998-2003.
AB  - BACKGROUND: Information is lacking on the prevalence and susceptibility patterns
      of bacterial isolates in dogs and cats with suspected hepatobiliary disease.
      OBJECTIVES: To characterize the prevalence, identity, and antimicrobial
      susceptibility of common hepatobiliary isolates from such patients. ANIMALS: Dogs
      and cats presented to the University of Wisconsin-Madison Veterinary Medical
      Teaching Hospital for which samples of bile, gallbladder, or liver were submitted
      for culture from 1998 to 2003, including 190 dogs (192 culture episodes) and 58
      cats (61 culture episodes). METHODS: Cases were identified from the microbiology
      laboratory database. Data from patient medical records were extracted, including
      the history of antimicrobial administration, the presence of fever, the results
      of CBC and serum biochemistry, the presence of biliary obstruction or
      hepatobiliary inflammation, and the results of aerobic and anaerobic bacterial
      cultures and aerobic antimicrobial susceptibilities. RESULTS: Biliary cultures
      yielded a significantly higher percentage of positive results overall (30% [18 of
      60]) than did hepatic cultures (7% [15 of 215]). In patients with cholecystitis,
      62% (8 of 13) had positive biliary cultures. In patients with hepatic
      inflammation, 23% (7 of 30) had positive bile cultures, whereas only 6% (6 of
      103) had positive hepatic cultures. Escherichia coli, Enterococcus spp.,
      Bacteroides spp., Streptococcus spp., and Clostridium spp. were the most common
      true-positive isolates. More than 80% of Enterobacteriaceae were susceptible to
      ciprofloxacin or aminoglycosides, with only 30-67% susceptible to first
      generation aminopenicillins and cephalosporins. Liver samples obtained by surgery
      or laparoscopy were more likely to yield positive cultures than those obtained by
      percutaneous needle biopsy.

PMID- 17552447
TI  - Single-agent pamidronate for palliative therapy of canine appendicular
      osteosarcoma bone pain.
AB  - BACKGROUND: Canine appendicular osteosarcoma (OSA) causes focal bone destruction,
      leading to chronic pain and reduced quality-of-life scores. Drugs that inhibit
      pathologic osteolysis might provide additional treatment options for managing
      cancer-induced bone pain. Aminobisphosphonates induce osteoclast apoptosis,
      thereby reducing pain associated with malignant osteolysis in human patients with
      cancer. HYPOTHESIS: Treatment of dogs with pamidronate administered intravenously
      will alleviate bone pain and reduce pathologic bone turnover associated with
      appendicular OSA in dogs. ANIMALS: Forty-three dogs with naturally occurring
      appendicular OSA administered pamidronate intravenously. METHODS: Prospective
      study. Therapeutic responses in dogs treated with pamidronate administered
      intravenously and nonsteroidal anti-inflammatory drugs (NSAID) were evaluated by
      using a numerical cumulative pain index score (CPIS), and by quantifying urine N
      telopeptide (NTx) excretion and relative primary tumor bone mineral density
      (rBMD) assessed with dual energy x-ray absorptiometry. In addition, variables,
      including pamidronate dose, skeletal mass, baseline and change for CPIS, urine
      NTx and rBMD during treatment, and baseline tumor volume and radiographic pattern
      were compared between dogs clinically responsive and nonresponsive to pamidronate
      therapy. RESULTS: Twelve of 43 dogs (28%) had pain alleviation for >4 months,
      lasting a median of 231 days. Changes in CPIS and rBMD during treatment were
      statistically different between responders and nonresponders (P = .046 and .03,
      respectively). CONCLUSIONS AND CLINICAL IMPORTANCE: Substantiated by reductions
      in CPIS and increases in rBMD, single-agent pamidronate administered
      intravenously with NSAID therapy relieves pain and diminishes pathologic bone
      turnover associated with appendicular OSA in a subset of dogs.

PMID- 17552448
TI  - Evaluation of antineutrophil IgG antibodies in persistently neutropenic dogs.
AB  - BACKGROUND: Immune-mediated neutropenia (IMN) is one of several causes of
      persistent neutropenia in dogs. A test to detect IMN in dogs is not available.
      HYPOTHESIS: A flow cytometric immunofluorescence assay will provide a sensitive
      method for detection of antineutrophil antibodies in dogs. ANIMALS: The study
      included 12 neutropenic dogs and 20 healthy dogs. METHODS: An indirect
      immunofluorescence assay was used to detect immunoglobulin G (IgG) binding to dog
      neutrophils. Leukoagglutination was evaluated by light microscopy. Neutrophil
      distribution in scatter plots, neutrophil fluorescence intensity, and the
      percentage of neutrophils with increased fluorescence intensity was evaluated by
      use of flow cytometry. RESULTS: Antineutrophil antibodies were detected in the
      serum of 5 of 6 dogs with a clinical diagnosis of IMN. Leukoagglutination was
      present in 3 dogs. Four dogs had altered neutrophil distribution in forward-angle
      versus side-angle light scatter plots. Five of 6 dogs had increased neutrophil
      fluorescence intensity and 4 of 6 dogs had an increased percentage of neutrophils
      with increased fluorescence intensity. CONCLUSIONS AND CLINICAL IMPORTANCE: The
      flow cytometric test for antineutrophil antibodies detects dogs with a clinical
      diagnosis of IMN. Testing for antineutrophil antibodies should include
      observation for leukoagglutination, observation of scatter plots for altered
      distribution of the neutrophil population, observation of the shape of the
      fluorescence histogram, determination of neutrophil fluorescence intensity, and
      determination of the percentage of neutrophils with increased fluorescence
      intensity.

PMID- 17552449
TI  - Effects of 4 classes of cardiovascular drugs on ventricular function in dogs with
      mitral regurgitation.
AB  - BACKGROUND: There have been few trials in which dogs with mitral regurgitation
      (MR) have been treated with various cardioactive drugs to determine effects on
      left ventricular (LV) function. HYPOTHESIS: Four classes of cardiovascular drugs
      may improve LV function in dogs with MR without increasing MR. ANIMALS: Nine
      mature dogs were included in the study. METHODS: MR was produced in 9 dogs. Five
      months later under butorphanol narcosis, parameters of LV function and left
      atrial dimension (LAD) were monitored by LV micromanometry and
      echocardiography/Doppler. Dogs were given (in random order) enalaprilat,
      nitroglycerine, ouabain, milrinone, and placebo. RESULTS: Nitroglycerin produced
      no significant change; milrinone and ouabain increased contractility; ouabain
      decreased heart rate; and there was evidence that enalaprilat and milrinone
      decreased LAD. Milrinone and ouabain decreased isovolumetric contraction time and
      therefore the time available for MR. There was no evidence that a positive
      inotrope increased MR despite increasing LV contractility and stroke volume.
      CONCLUSION AND CLINICAL IMPORTANCE: This study contradicts the hypotheses that
      (1) strengthening the left ventricle may increase MR and (2) treatment of MR
      (even before symptoms of heart failure develop) may decrease LAD. It is
      reasonable that strengthening the force of LV contraction should increase the
      driving pressure for MR; however, this effect did not appear to increase MR.
      Although some investigators believe that treating dogs with MR with afterload
      reducers and decreasing hindrance to ejection of blood from the LV to aorta may
      lengthen life by decreasing MR, there did not appear to be a reduction in MR, at
      least in response to the angiotensin-converting enzyme (ACE) inhibitor.

PMID- 17552450
TI  - Hemostatic biomarkers in dogs with chronic congestive heart failure.
AB  - BACKGROUND: Chronic congestive heart failure (CHF) in humans is associated with
      abnormal hemostasis, and abnormalities in hemostatic biomarkers carry a poor
      prognosis. Alterations in hemostatic pathways can be involved in the pathogenesis
      of CHF in dogs, and microthrombosis in the myocardium could contribute to
      increased mortality. HYPOTHESIS: That plasma concentration or activity of
      hemostatic biomarkers is altered in dogs with CHF and that these factors predict
      mortality. ANIMALS: Thirty-four dogs with CHF caused by either dilated
      cardiomyopathy (DCM, n=14) or degenerative valvular disease (CDVD, n=20) compared
      with 23 healthy age-matched control dogs were included in this study. Dogs with
      CHF were recruited from 2 referral cardiology clinics, and control dogs were
      owned by friends or colleagues of the investigators. METHODS: Clinical
      examination and echocardiography were performed in all dogs. Plasma fibrinogen
      and D-dimer concentrations, antithrombin and protein C activity, and thrombin
      antithrombin complex (TAT) were measured in all dogs. RESULTS: Dogs with CHF had
      significantly higher fibrinogen (P = .04), D-dimer (P = .002), and TAT
      concentration (P < .0001), lower antithrombin (P < .0001) and protein C activity
      (P < .001) compared with control dogs. None of the hemostatic biomarkers were
      associated with risk of death. CONCLUSIONS AND CLINICAL IMPORTANCE: There is
      evidence of a procoagulant state in dogs with CHF. The lack of predictive value
      for survival might be due to the small number of dogs examined. Further studies
      are necessary to investigate the presence and importance of microthrombosis in
      dogs with CHF.

PMID- 17552451
TI  - A novel mutation of the CLCN1 gene associated with myotonia hereditaria in an
      Australian cattle dog.
AB  - BACKGROUND: Heritable myotonia is a genetic muscle disorder characterized by slow
      relaxation of skeletal muscles. The main clinical signs are skeletal muscle
      stiffness, especially after vigorous contraction, and muscle hypertrophy. Muscle
      stiffness may be enhanced by inactivity, and often is relieved by exercise.
      Myotonia can be inherited in an autosomal dominant or recessive manner (Thomsen-
      or Becker-type myotonia, respectively). In mice, goats, Miniature Schnauzer dogs,
      and most affected humans, the disorder is caused by mutations in CLCN1, which
      encodes the skeletal muscle voltage-gated chloride channel, Cl1C-1. HYPOTHESIS:
      We hypothesized that an Australian Cattle Dog with generalized muscle stiffness
      and hypertrophy examined at the Ontario Veterinary College would have a mutation
      in the CLCN1 gene. ANIMALS: A pure-bred Australian Cattle Dog from Ontario,
      Canada, was used. METHODS: Based on clinical signs and electromyographic test
      results, a diagnosis of myotonia hereditaria was made, and a muscle biopsy was
      collected for genetic analysis. RESULTS: Sequence data obtained from the affected
      dog confirmed that it was homozygous for a single base insertion in the CLCN1
      coding sequence. This mutation would result in a truncated ClC-1 protein being
      expressed, which, based on molecular evidence from other studies, would result in
      functionally compromised chloride conduction in the skeletal muscles of the
      animal. CONCLUSIONS AND CLINICAL IMPORTANCE: To the authors' knowledge, this
      report describes the Ist case of myotonia in an Australian Cattle Dog and
      represents the 1st non-Schnauzer canine myotonia to be genetically characterized.
      In addition, we developed a polymerase chain reaction-based genetic screen to
      detect heterozygotes with this mutation in the at-large Australian Cattle Dog
      population.

PMID- 17552452
TI  - Benign familial juvenile epilepsy in Lagotto Romagnolo dogs.
AB  - BACKGROUND: Idiopathic childhood epilepsies with benign outcomes are well
      recognized in human medicine, but are not reported in veterinary literature. We
      recognized such a neurologic syndrome in Lagotto Romagnolo dogs. ANIMALS: Twenty
      five Lagotto Romagnolo puppies from 9 different litters examined because of
      simple or complex focal seizures and 3 adult Lagotto Romagnolo dogs exhibiting
      similar clinical signs were used. METHODS: Clinical and diagnostic evaluations of
      affected dogs were conducted, including electromyography, electroencephalography,
      and other testing. RESULTS: Seizures in puppies began at 5 to 9 weeks of age and
      usually resolved spontaneously by 8 to 13 weeks. Those with the most severe
      seizures also had signs of neurologic disease between these seizures, including
      generalized ataxia and hypermetria. There were no abnormalities in routine
      laboratory screenings of blood, urine, and cerebrospinal fluid. Electromyography,
      brainstem auditory-evoked potentials, and magnetic resonance imaging revealed no
      specific and consistent abnormalities. Fourteen of 16 (87.5%) affected puppies
      and 2 of 3 (67%) adult dogs revealed epileptiform activity in the
      electroencephalogram. Histopathologic examination in 1 puppy and 1 adult dog
      revealed lesions of Purkinje cell inclusions and vacuolation of their axons
      restricted to the cerebellum. Pedigree analysis suggests an autosomal recessive
      mode of inheritance. CONCLUSIONS AND CLINICAL IMPORTANCE: This disorder, with
      simple or complex focal seizures and cerebellar lesions, represents a newly
      recognized epileptic syndrome in dogs.

PMID- 17552453
TI  - Effects of 2 concentrations of sodium citrate on coagulation test results, von
      Willebrand factor concentration, and platelet function in dogs.
AB  - BACKGROUND: Blood collection tubes containing 3.2% (0.109 M) sodium citrate,
      instead of 3.8% (0.129 M) sodium citrate, have recently become available in the
      United States. These tubes are visually indistinguishable from the traditional
      3.8% sodium citrate tubes, except for wording on the label. Consequently, samples
      for hemostatic evaluation are frequently collected in tubes containing the lower
      concentration of sodium citrate. HYPOTHESIS: Results of hemostasis assays are
      different in samples collected in 3.2% versus 3.8% sodium citrate. ANIMALS:
      Twenty healthy dogs. METHODS: This study aimed at determining whether results of
      standard coagulation tests, von Willebrand factor concentration (vWF:Ag), and
      platelet function with the platelet function analyzer PFA-100a were affected by
      the different concentrations of sodium citrate. Blood samples were collected in
      tubes containing either 3.2% or 3.8% sodium citrate concentrations and processed
      routinely for coagulation assays (one-stage prothrombin time [OSPT], activated
      partial thromboplastin time [aPTT], fibrinogen concentration, and platelet
      count), vWF:Ag, and platelet function assays with a PFA-100. RESULTS: There was
      no significant difference between samples collected in 3.2% versus those
      collected in 3.8% sodium citrate for OSPT, aPTT, fibrinogen concentration,
      platelet count, or vWF:Ag. The closure times with collagen/adenosine diphosphate
      were significantly shorter (66 +/- 8.1 versus 74.8 +/- 9.7 seconds; P < .0001)
      with the 3.2% than with 3.8% sodium citrate concentration, and the hematocrit was
      significantly higher (47.9 +/- 5.6 versus 46.0 +/- 4.7 seconds; P = .03) in
      samples collected in 3.2% than in those collected in 3.8% sodium citrate.
      CONCLUSIONS AND CLINICAL IMPORTANCE: There is no clinically relevant effect of
      collection of blood into 3.2% or 3.8% sodium citrate.

PMID- 17552454
TI  - Effects of syringe type and storage temperature on results of blood gas analysis
      in arterial blood of horses.
AB  - BACKGROUND: Results of arterial blood gas analysis can be biased by pre
      analytical factors, such as time to analysis, syringe type, and temperature
      during storage. However, the acceptable delay between time of collection and
      analysis for equine arterial blood gas remains unknown. HYPOTHESIS: Dedicated
      plastic syringes provide better stability of arterial blood gases than
      multipurpose plastic syringes. ANIMALS: Eight mares, 1 stallion, and 1 gelding,
      ages 3 to 10 years old. METHODS: Arterial blood samples were collected in a glass
      syringe, a plastic syringe designated for blood gas collection, and a
      multipurpose tuberculin plastic syringe. Blood samples were stored at ambient
      temperature or in iced water. For each sample, partial pressure of oxygen in
      arterial blood (PaO2), partial pressure of carbon dioxide in arterial blood
      (PaCO2), and pH were measured within a few minutes of collection and at 5, 20,
      30, 60, 90, and 120 minutes after collection. RESULTS: Collection into glass
      syringes stored in iced water provided adequate PaO2 results for up to 117 +/- 35
      minutes, whereas blood collected in either of the plastic syringes resulted in a
      variation >10 mm Hg after 10 +/- 3 to 17 +/- 2 minutes, depending on the storage
      conditions. Plastic syringes kept at ambient temperature offered more stability
      for PaCO2 analysis because they could be stored up to 83 +/- 16 minutes without
      significant variations. Values of pH did not show variations more than 0.02 for
      the first hour, irrespectively of storage condition. CONCLUSIONS AND CLINICAL
      IMPORTANCE: Glass syringes placed on ice are preferable for analysis of PaO2.
      Blood collected in plastic syringes should be analyzed within 10 minutes,
      irrespective of the storage temperature, to ensure the accuracy of PaO2 values.

PMID- 17552456
TI  - Serum iron and plasma fibrinogen concentrations as indicators of systemic
      inflammatory diseases in horses.
AB  - BACKGROUND: Detection of systemic inflammation, which is important for proper
      diagnosis and prompt treatment, can be challenging. HYPOTHESIS: Measurement of
      plasma iron concentration is a sensitive method for detecting systemic
      inflammation in horses compared with measurements of plasma fibrinogen
      concentration, a traditional marker for inflammation in the horse. ANIMALS:
      Ninety-seven horses hospitalized with diseases causing systemic inflammation, 22
      horses with localized inflammation, and 12 clinically normal horses were included
      in this study. METHODS: A retrospective study was made on hospitalized horses
      that had both plasma iron and fibrinogen concentrations measured on hospital
      admission. RESULTS: Plasma iron concentration was lower in horses with systemic
      inflammation (64 +/- 45 microg/dL) than the reference interval minimum (105
      microg/dL) and were significantly lower (P = .001) than the value in a group of
      horses with local inflammation (123 +/- 45 microg/dL) and in healthy transported
      horses (143 +/- 29 microg/dL). Low plasma iron and high fibrinogen concentrations
      were both sensitive indicators of systemic inflammation in horses with
      sensitivity of 90 and 82%, respectively. There was a similar correlation between
      either continued decreases in iron concentration (Rsp of 0.239) or increases in
      fibrinogen concentration (Rsp of 0.280) during hospitalization and a worse
      prognosis. CONCLUSIONS AND CLINICAL IMPORTANCE: Measurement of plasma iron
      concentration better reflected acute inflammation than did fibrinogen
      concentration.

PMID- 17552455
TI  - Cytokine profiles of peripheral blood mononuclear cells isolated from septic and
      healthy neonatal foals.
AB  - BACKGROUND: Septicemia initiates the production of pro-inflammatory (interleukin
      [IL] 1-beta [IL-1beta], interferon-gamma [IFN-gamma], IL-6), and anti
      inflammatory (IL-4) cytokines. The transcription of some of these proteins (IL-8,
      IL-6) is linked to endotoxin-induced activation of the toll-like receptor 4
      (TLR4) on peripheral blood mononuclear cells (PBMC). HYPOTHESES: Septic foals
      fail to increase gene expression of IFN-gamma. Nonsurviving septic foals exhibit
      distinctive cytokine profiles. ANIMALS: Twenty-one septic and 20 healthy neonatal
      foals. METHODS: Using real-time polymerase chain reaction, gene expression of IFN
      gamma, IL-1beta, IL-6, IL-4, IL-8, TLR4, and beta-actin in PBMC were measured in
      samples obtained from septic foals at 0, 24, and 72 hours (T = 0, 24, and 72
      hours) after admission to the Cornell University Hospital for Animals. Control
      foals were sampled at comparable times. RESULTS: At T=0 hours, septic foals
      exhibited a 6-fold decrease in gene expression of IL-4 and a 5-fold increase in
      gene expression of TLR4. Gene expression of IFN-gamma, IL-6, IL-8, or of IL-1beta
      did not differ between the 2 groups of foals at T = 0 hours. In septic foals that
      died (n = 3), there was a 15-fold increase in IL-6 at T = 0 hours compared to
      survivors. CONCLUSIONS AND CLINICAL IMPORTANCE: Septic foals, unlike septic human
      infants, up-regulate TLR4 gene expression, which may enhance pro-inflammatory
      cytokine production. Despite the presence of sepsis, IFN-gamma was not up
      regulated. Additional studies are needed to verify that increased IL-6 expression
      is associated with a poor prognosis in septic foals.

PMID- 17552457
TI  - Suspected immune-mediated myositis in horses.
AB  - BACKGROUND: Although immune-mediated myositis (IMM) is commonly reported in other
      species, this condition is poorly described in horses. HYPOTHESIS: IMM occurs in
      horses. ANIMALS: Thirty-seven horses with suspected IMM were included in the
      study. METHODS: The database of the Neuromuscular Diagnostic Laboratory was
      reviewed to identify 37 horses with muscle biopsies characterized by lymphocytic
      infiltrates. A retrospective standardized questionnaire regarding clinical signs
      and response to treatment was answered by horse owners. RESULTS: Horses with
      suspected IMM were predominantly of Quarter Horse bloodlines (33/37 horses) and
      primarily either < or =8 years or > or =17 years of age. Clinical signs included
      rapid atrophy, particularly of the epaxial and gluteal muscles, depression, and
      stiffness. Creatine kinase (CK) activity (mean 9746; range 260-139,183 U/L:
      reference range 119-287 U/L) and aspartate transaminase (AST) activity (mean
      2880; range 350-9009 U/L: reference range 138-409 U/L) were high. Exposure to
      horses with infectious respiratory disease occurred in 39% (9/23) of horses
      before clinical signs and 47% (9/19) had recurrence of atrophy. Variation in
      dosage and time elapsed before administration of corticosteroids confounded
      assessment of treatment efficacy. Macrophages and CD4+ T lymphocytes were the
      prominent mononuclear cellular infiltrates with lesser numbers of CD8+ cells and
      small clusters of B lymphocytes in some samples. Myofibers did not stain for
      equine immunoglobulin G (IgG). CONCLUSIONS AND CLINICAL IMPORTANCE: IMM appears
      to be a distinct cause of rapid muscle atrophy, particularly in Quarter Horses
      that may be amenable to treatment with corticosteroids. Diagnosis is best
      achieved by identifying lymphocytic infiltrates in atrophied muscles.

PMID- 17552458
TI  - Thoracic percussion to determine the caudal lung border in healthy horses.
AB  - BACKGROUND: The application of equine thoracic percussion has been ignored
      because of the availability of modern imaging techniques. Ultrasonography is a
      reliable tool in determining the caudal lung border of horses. The aim of the
      study was to compare percussion with ultrasonography to determine lung borders in
      horses. HYPOTHESIS: That thoracic percussion can detect the caudal lung border
      and that its accuracy is comparable with thoracic ultrasonography. ANIMALS:
      Fifteen randomly chosen, healthy, Warmblood horses. METHODS: The caudal lung
      border was detected by percussion and ultrasonography at the end of inspiration
      and expiration on both sides of the thorax. A reference point close to the
      withers was determined, allowing standardized measurements. The distance between
      this point and the caudal lung border in different intercostal spaces (ICS) was
      measured by a tape measure. RESULTS: No significant difference was found between
      percussional and ultrasonographic results. Greater differences were found between
      inspiration and expiration by ultrasonography compared with percussion in all
      intercostal spaces on both sides of the thorax. It was significant (P = .028) in
      the 12th ICS in the right hemithorax. CONCLUSIONS AND CLINICAL IMPORTANCE:
      Percussion is a reliable tool to determine the caudal lung border in healthy
      horses. Differences caused by the displacement of the lung during respiration
      should be taken into consideration when applying either method.

PMID- 17552459
TI  - Serum bile acids concentrations in healthy and clinically ill neonatal foals.
AB  - BACKGROUND: Reference ranges for serum bile acids (SBA) concentration are well
      established in healthy adult horses. Increased values are indicative of hepatic
      disease. HYPOTHESES: SBA concentrations are significantly greater in the neonatal
      period compared with mature horses, and illness in the neonatal period will
      further increase SBA. ANIMALS: Ten healthy mature horses, 12 healthy foals, and
      31 clinically ill foals. METHODS: Prospective cross-sectional study. Blood
      samples were obtained once from the mature horses, from healthy foals immediately
      after birth, at 2 days, and at 1, 2, 3, 4, and 6 weeks of age; and from ill foals
      less than 1 month of age at the time of admission to the Veterinary Teaching
      Hospital. SBA concentrations were determined enzymatically and by
      radioimmunoassay. Total and direct bilirubin and triglyceride concentrations were
      measured, as well as sorbitol dehydrogenase (SDH) and gamma-glutamyltransferase
      (GGT) activities. RESULTS: There was a significant negative correlation between
      age and SBA concentration. Compared with mature horses, SBA concentrations were
      significantly greater in healthy foals at each collection time over the first 6
      weeks of life. Radioimmunoassay values were lower than enzymatic SBA values, with
      increasing bias as the mean difference between values increased. When comparing
      age-matched values between healthy and ill foals, there were no significant
      differences in SBA. None of the ill foals had a primary diagnosis of hepatic
      disease. There was no significant correlation between the SBA concentration and
      the bilirubin or triglyceride concentrations or the GGT activity. There was a
      significant direct correlation between increased SBA and serum SDH activity in
      healthy foals only. CONCLUSION AND CLINICAL IMPORTANCE: SBA concentrations in
      foals are significantly higher in the early neonatal period, underscoring the
      importance of using age-matched references when evaluating clinical pathology
      values during the neonatal period.

PMID- 17552460
TI  - Hemorrhagic syndrome-like disease in calves with bovine viral diarrhea and
      mucosal disease complex.
AB  - BACKGROUND: Bovine viral diarrhea virus (BVDV) infection is one of the causes of
      hemorrhagic diathesis in cattle but there have been limited field studies about
      that condition. HYPOTHESIS: To identify the cause of hemorrhagic diathesis in
      calves and describe its clinical findings. ANIMALS: Five calves from a farm with
      150 dairy cows. METHODS: Clinical examination of the calves was performed. After
      blood samples were obtained from 2 calves, whole blood, sera, and leukocyte
      samples were used for hematologic and hemostatic examinations, neutralization
      tests, virus isolation, and viral genome sequencing. RESULTS: The calves had
      moderate pyrexia, dullness, serous or mucous nasal discharge, and petechial and
      ecchymotic hemorrhages on mucosal surfaces. Severe thrombocytopenia and anemia
      were identified on hematologic examinations. All calves died within 10 days of
      the onset of clinical signs. Virologic examinations identified BVDV as the
      causative agent of the disease. CONCLUSIONS AND CLINICAL IMPORTANCE: This paper
      identifies a hemorrhagic syndrome-like disease in calves with bovine viral
      diarrhea and mucosal disease complex in Turkey.

PMID- 17552461
TI  - Culture-positive sepsis in neonatal camelids: 21 cases.
AB  - BACKGROUND: There is limited literature on neonatal bacterial sepsis in New World
      (NW) camelids. HYPOTHESIS: Bacterial culture-positive crias have clinical
      differences based on the specific bacterial genera isolated. ANIMALS: Bacterial
      culture-positive NW camelid crias <21 days of age from 1990 to 2005 were
      included. METHODS: Historic physical examination and cliniopathologic data were
      retrieved from medical records as were the identity and antibiograms of bacterial
      isolates. Cases were categorized by outcome (survival versus nonsurvival) and
      type of sepsis (gram-negative or gram-positive). Kruskal-Wallis and chi-square
      testing were used to evaluate differences between groups. RESULTS: Twenty-one
      crias met the inclusion criteria. Median age was 2 days. Failure of passive
      transfer was common. There were few differences identified on the basis of
      outcome or type of sepsis. Crias without gastrointestinal or central nervous
      system involvement survived in greater numbers. Forty-six percent of isolates
      were gram-positive. The most common isolates were the following: Escherichia
      coli, Enterococcus spp., Listeria monocytogenes, and Citrobacter spp. Overall
      survival was 67% (14/21). CONCLUSIONS AND CLINICAL IMPORTANCE: Crias with sepsis
      do not appear to present with major biochemical, hematologic, or blood gas
      abnormalities, potentially complicating diagnosis. Affected crias may not have
      localizing signs at presentation and are not usually febrile, although
      hypothermia, tachypnea, and tachycardia are relatively common. Total protein
      concentration was not a substitute for immunoglobulin G measurement in septic
      crias in this study. Familiarity with the clinical presentation and common
      pathogens isolated should improve early recognition and treatment and ultimately
      outcome of crias with sepsis.

PMID- 17552462
TI  - Dissection of a patent ductus arteriosus with right heart failure in an adult
      dog.

PMID- 17552463
TI  - Neuroaxonal dystrophy in dogs: case report in 2 litters of Papillon puppies.

PMID- 17552464
TI  - Brainstem abscess due to plant foreign body in a dog.

PMID- 17552465
TI  - Altered tryptophan metabolism in FIV-positive cats.
AB  - BACKGROUND: Feline immunodeficiency virus (FIV) is analogous to human
      immunodeficiency virus, the causative agent of human acquired immunodeficiency
      syndrome (AIDS). In AIDS patients, a progressive reduction in serum tryptophan
      concentration occurs because of activation of an inducible tryptophan degradation
      pathway mediated by elevated lamda-interferon production. HYPOTHESIS: Cats
      infected with FIV have increased tryptophan catabolism evidenced by reduced
      circulating concentrations of tryptophan and increased concentrations of the
      tryptophan catabolite kynurenine. ANIMALS: Convenience sample of 235 cats
      submitted for diagnostic FIV serology (115 FIV-negative and 120 FIV-positive
      cats). METHODS: Retrospective, cross-sectional study. Serum was assayed for
      tryptophan and kynurenine using a high performance liquid chromatography assay
      with fluorescence and ultraviolet detection, respectively. RESULTS: Tryptophan
      and kynurenine concentrations were log-normally distributed. Geometric mean
      concentrations were: tryptophan: FIV-positive 30.6 microM (95% CI: 26.8 34.8
      microM), FIV-negative 48.9 [microM (95% CI: 43.6-54.9 microM) (P < .001);
      kynurenine: FIV-positive 22.7 microM (95% CI: 25.5-10.9 microM), FIV-negative 9.9
      microM (95% CI: 20.3-9.03 microM) (P < .001). The ratio of kynurenine to
      tryptophan was: FIV-positive 4.93 (95% CI: 5.62-4.32), FIV-negative 1.34 (95% CI:
      1.53 1.17) (P < .0001). CONCLUSIONS AND CLINICAL IMPORTANCE: Serum tryptophan
      concentration was significantly lower and serum kynurenine concentration was
      significantly higher in FIV-positive cats. The kynurenine: tryptophan ratio was
      >3-fold higher in FIV-positive animals, indicating increased tryptophan
      catabolism in this group. Dietary or pharmacologic intervention to support serum
      tryptophan concentrations has been shown to be clinically useful in humans with
      AIDS and might be applicable to cats with FIV infection.

PMID- 17552466
TI  - Guidelines for the identification, evaluation, and management of systemic
      hypertension in dogs and cats.

PMID- 17552467
TI  - Methodological considerations in performing semantic- and translation-priming
      experiments across languages.
AB  - Research in the field of bilingualism has had as its principal aim to describe
      the structure and function of memory for bilingual speakers. A primary technique
      that has been used to examine bilingual memory is an examination of cross
      language word priming (semantic and translation), using the lexical decision and
      pronunciation tasks. Although studies have, on occasion, revealed greater degrees
      of word priming from a dominant to a subordinate language, in comparison with the
      reverse, a careful review of the methodology that has been used reveals a number
      of issues that render conclusions such as this quite problematic. Parameters of
      concern include language proficiency, cognate status, masking, control
      conditions, word frequency and length, stimulus onset asynchrony, relatedness
      proportion, and nonword ratio. These factors are discussed, as well as
      recommendations for conducting future empirical research in this area of
      investigation.

PMID- 17552468
TI  - jTRACE: a reimplementation and extension of the TRACE model of speech perception
      and spoken word recognition.
AB  - This article describes jTRACE, a freely available, cross-platform Java
      reimplementation of the TRACE model of spoken word recognition. The goal of the
      reimplementation is to facilitate the use of simulations by researchers who may
      not have the skills or time necessary to use or extend the original C
      implementation. In this article, we report a large-scale validation project, in
      which we have replicated a number of important previous simulations, and then we
      describe several new features in jTRACE designed to help researchers conduct
      original TRACE research, as well as to replicate earlier findings. These features
      include visualization tools, powerful scripting, built-in data graphing,
      adjustable levels of external and internal noise, and adjustable lexical
      characteristics, such as frequency of occurrence. Functions for saving and
      reloading entire simulations facilitate archiving, sharing, and replication and
      also make jTRACE ideal for educational use, since it comes bundled with several
      important simulations. jTRACE can be downloaded from
      magnuson.psy.uconn.edu/jtrace.

PMID- 17552469
TI  - Analyzing individual differences in sentence processing performance using
      multilevel models.
AB  - The use of multilevel models is increasingly common in the behavioral sciences
      for analyzing hierarchically structured data, including repeated measures data.
      These models are flexible and easily implemented via a variety of commercially
      available statistical software programs. We consider their application in the
      context of an eye-movement experiment testing readers' responses to a semantic
      plausibility manipulation in temporarily ambiguous sentences. Multilevel models
      were used to study the relationship between working memory capacity and the
      extent to which readers were disrupted by syntactic misanalysis. This represented
      a cross-level interaction between an individual difference measure and a sentence
      level characteristic. We compare a multilevel modeling approach to a standard
      approach based on ANOVA.

PMID- 17552470
TI  - Observer agreement for event sequences: methods and software for sequence
      alignment and reliability estimates.
AB  - When sequences of discrete events, or other units, are independently coded by two
      coders using a set of mutually exclusive and exhaustive codes, but the onset
      times for the codes are not preserved, it is often unclear how pairs of protocols
      should be aligned. Yet such alignment is required before Cohen's kappa, a common
      agreement statistic, can be computed. Here we describe a method--based on the
      Needleman and Wunsch (1970) algorithm originally devised for aligning nucleotide
      sequences--for optimally aligning such sequences; we also offer the results of a
      simulation study of the behavior of alignment kappa with a number of variables,
      including number of codes, varying degrees of observer accuracy, sequence length,
      code variability, and parameters governing the alignment algorithm. We conclude
      that (1) under most reasonable circumstances, observer accuracies of 90% or
      better result in alignment kappas of .60 or better; (2) generally, alignment
      kappas are not strongly affected by sequence length, the number of codes, or the
      variability in the codes' probability; (3) alignment kappas are adversely
      affected when missed events and false alarms are possible; and (4) cost matrices
      and priority orders used in the algorithm should favor substitutions (i.e.,
      disagreements) over insertions and deletions (i.e., missed events and false
      alarms). Two computer programs were developed: Global Sequence Alignment, or GSA,
      for carrying out the simulation study, and Event Alignment, or ELign, a user
      oriented program that computes alignment kappa and provides the optimal alignment
      given a pair of event sequences.

PMID- 17552471
TI  - The measurement of left-right asymmetries in the Simon effect: a fine-grained
      analysis.
AB  - The spatial Simon effect is often asymmetric, being greater on one side than on
      the other. To date, not much attention has been paid to these asymmetries, and
      explanations of the Simon effect do not take them into account. In the present
      article, we attempt to clarify the statistical implications of the asymmetries so
      as to provide a useful tool for future empirical investigation. Starting with
      examples from our laboratory and previous well-known studies, we point out the
      consequences of ignoring the asymmetries in the Simon effect. We suggest an
      alternative data analysis that might render the results clearer. Finally, through
      a comparison of left- and right-handed subjects, we demonstrate that asymmetries
      in the Simon effect are linked to the lateralization of processes involved in the
      Simon task--that is, attention and response selection. This approach provides a
      strong argument against collapsing data from the two sides to measure the Simon
      effect.

PMID- 17552473
TI  - SAS and SPSS macros to calculate standardized Cronbach's alpha using the upper
      bound of the phi coefficient for dichotomous items.
AB  - Cronbach's a is widely used in social science research to estimate the internal
      consistency of reliability of a measurement scale. However, when items are not
      strictly parallel, the Cronbach's a coefficient provides a lower-bound estimate
      of true reliability, and this estimate may be further biased downward when items
      are dichotomous. The estimation of standardized Cronbach's a for a scale with
      dichotomous items can be improved by using the upper bound of coefficient phi.
      SAS and SPSS macros have been developed in this article to obtain standardized
      Cronbach's a via this method. The simulation analysis showed that Cronbach's a
      from upper-bound phi might be appropriate for estimating the real reliability
      when standardized Cronbach's a is problematic.

PMID- 17552472
TI  - Variations of the flanker paradigm: assessing selective attention in young
      children.
AB  - The development of selective attention and associated self-regulatory processes
      was assessed in young children, ages 4, 5, and 6, through the use of three
      alternative versions of the flanker paradigm utilizing colors, shapes, and fish.
      These variations were used to examine the influence of task differences on
      children's performance. The presence of cognitive self-regulatory strategies in
      young children was also assessed. Significant flanker interference effects,
      marked by significant task-linked response time differences, were found across
      all three versions of the paradigm. Although a significant portion of children
      demonstrated self-regulatory abilities, not every participant demonstrated the
      specific strategies of self-monitoring and response control. Furthermore, these
      differences were evident across all age groups. The implications of these results
      are discussed within the theoretical context of task development, taking into
      consideration the need to modify computerized attention paradigms for use with
      young children in order to reliably measure cognitive constructs across children
      and adults.

PMID- 17552474
TI  - Graphing within-subjects confidence intervals using SPSS and S-Plus.
AB  - Within-subjects confidence intervals are often appropriate to report and to
      display. Loftus and Masson (1994) have reported methods to calculate these, and
      their use is becoming common. In the present article, procedures for calculating
      within-subjects confidence intervals in SPSS and S-Plus are presented (an R
      version is on the accompanying Web site). The procedure in S-Plus allows the user
      to report the bias corrected and adjusted bootstrap confidence intervals as well
      as the standard confidence intervals based on traditional methods. The presented
      code can be easily altered to fit the individual user's needs.

PMID- 17552475
TI  - Extending the CLAST sequential rule to one-way ANOVA under group sampling.
AB  - Several studies have demonstrated that the fixed-sample stopping rule (FSR), in
      which the sample size is determined in advance, is less practical and efficient
      than are sequential-stopping rules. The composite limited adaptive sequential
      test (CLAST) is one such sequential-stopping rule. Previous research has shown
      that CLAST is more efficient in terms of sample size and power than are the FSR
      and other sequential rules and that it reflects more realistically the practice
      of experimental psychology researchers. The CLAST rule has been applied only to
      the t test of mean differences with two matched samples and to the chi-square
      independence test for twofold contingency tables. The present work extends
      previous research on the efficiency of CLAST to multiple group statistical tests.
      Simulation studies were conducted to test the efficiency of the CLAST rule for
      the one-way ANOVA for fixed effects models. The ANOVA general test and two linear
      contrasts of multiple comparisons among treatment means are considered. The
      article also introduces four rules for allocating N observations to J groups
      under the general null hypothesis and three allocation rules for the linear
      contrasts. Results show that the CLAST rule is generally more efficient than the
      FSR in terms of sample size and power for one-way ANOVA tests. However, the
      allocation rules vary in their optimality and have a differential impact on
      sample size and power. Thus, selecting an allocation rule depends on the cost of
      sampling and the intended precision.

PMID- 17552476
TI  - Multilevel models for the experimental psychologist: foundations and illustrative
      examples.
AB  - Although common in the educational and developmental areas, multilevel models are
      not often utilized in the analysis of data from experimental designs. This
      article illustrates how multilevel models can be useful with two examples from
      experimental designs with repeated measurements not involving time. One example
      demonstrates how to properly examine independent variables for experimental
      stimuli or individuals that are categorical, continuous, or semicontinuous in the
      presence of missing data. The second example demonstrates how response times and
      error rates can be modeled simultaneously within a multivariate model in order to
      examine speed-accuracy trade-offs at the experimental-condition and individual
      levels, as well as to examine differences in the magnitude of effects across
      outcomes. SPSS and SAS syntax for the examples are available electronically.

PMID- 17552477
TI  - A high-sensitivity drinkometer circuit with 60-Hz filtering.
AB  - This article describes a drinkometer circuit designed to (1) detect licks even if
      the resistance of the skin on the animal's feet becomes quite high due to low
      humidity, (2) automatically adjust its triggering threshold and increase its gain
      so that it will continue to detect licks when the water delivery spout is
      partially shorted to ground by high ambient humidity, (3) reject 60-Hz signals so
      they will not be treated as rapid licks by the data-recording system, and (4)
      tolerate the high voltages that can occur if the subject receives an electric
      shock while drinking. This lickometer will be especially useful in situations
      where it is not practical to monitor for possible signal failure due to high or
      low humidity, or where 60-Hz artifacts may contaminate the signal provided to a
      recording computer.

PMID- 17552478
TI  - Calibration algorithm for eyetracking with unrestricted head movement.
AB  - This article reports a calibration procedure that enables researchers to track
      movements of the eye while allowing relatively unrestricted head and/or body
      movement. The eye-head calibration algorithm calculates fixation point based on
      eye-position data acquired by a head-mounted eyetracker and corresponding head
      position data acquired by a 3-D motion-tracking system. In a single experiment,
      we show that this procedure provides robust eye-position estimates while allowing
      free head movement. Although several companies offer ready-made systems for this
      purpose, there is no literature available that makes it possible for researchers
      to explore the details of the calibration procedures used by these systems. By
      making such details available, we hope to facilitate the development of cost
      effective, nonproprietary eyetracking solutions.

PMID- 17552479
TI  - Loudspeaker equalization for auditory research.
AB  - The equalization of loudspeaker frequency response is necessary to conduct many
      types of well-controlled auditory experiments. This article introduces a program
      that includes functions to measure a loudspeaker's frequency response, design
      equalization filters, and apply the filters to a set of stimuli to be used in an
      auditory experiment. The filters can compensate for both magnitude and phase
      distortions introduced by the loudspeaker. A MATLAB script is included in the
      Appendix to illustrate the details of the equalization algorithm used in the
      program.

PMID- 17552480
TI  - Experimental comparison of dyspnea and pain.
AB  - Dyspnea and pain are similarly unpleasant, alarming physical sensations, but
      studies examining both sensations in combination are lacking. In the present
      study, dyspnea was induced in 7 healthy volunteers by breathing through
      inspiratory resistive loads and the effects were compared with those of a heat
      pain stimulus. End-tidal partial pressures of carbon dioxide (PET(CO2)),
      inspiratory time (Ti), breathing frequency (f), experienced unpleasantness, and
      intensity were measured. No difference was observed between dyspnea and pain in
      experienced intensity and unpleasantness (p > .05). During dyspneic stimulation,
      slightly higher Ti was found than for pain (p < .08). PET(CO2) showed slight
      increases during the dyspneic versus the baseline and painful conditions
      (deltaPET(CO2) = 1.5 and 1.3 mmHg, respectively; p < .01 andp < .05). This study
      shows that the effects of dyspnea and heat pain can be compared within one
      experiment; both stimuli can be presented with similar intensity and
      unpleasantness, which is a prerequisite for comparing responses to them. The
      changes in PET(CO2) between our conditions were minimal, allowing an application
      of the present design to future fMRI studies.

PMID- 17552481
TI  - Development of the Real-Time Subjective Emotionality Assessment (RTSEA) system.
AB  - A new Real-Time Subjective Emotionality Assessment (RTSEA) system was developed
      for this study. The system is composed of two parts: an emotionality input and
      evaluation parts. An experiment was conducted in order to investigate the
      effectiveness of the RTSEA system. The present study compared Galvanic Skin
      Response (GSR) with the RTSEA by presenting 28 subjects with pictures that
      aroused either positive or negative emotion. Following the experiment, a
      subjective assessment using a questionnaire was given to the same subjects.
      According to the correlation coefficients, changes of the RTSEA had strong
      correlations with the changes of the GSR. Also, the questionnaire results showed
      marked similarity to the average responses of the RTSEA. In conclusion, the most
      remarkable characteristic of the present system is that it not only assesses the
      average emotionality when stimuli are presented, but also shows the trend of
      change in emotionality over time.

PMID- 17552482
TI  - Word lists for testing cognitive biases toward body shape among men and women.
AB  - The present study developed word lists describing three categories of body build-
      fat, thin, and muscular--for use in investigating cognitive risk factors for body
      dissatisfaction. Fifty-one men and 51 women rated the categorization, valence,
      and familiarity of 284 body-related adjectives in order to develop the final
      lists. The normative frequency of each of the 284 words was determined using an
      index of American English. The final 19- to 26-item word lists were constructed
      so that the average number of syllables, word length, word frequency, and mean
      percentage of categorization agreement were comparable. The availability of these
      word lists will facilitate future cognitive research into a key risk factor for
      eating disorders.

PMID- 17552483
TI  - A procedure for studying online conversational processing using a chat bot.
AB  - This article reports the development of a tool for examining the social and
      cognitive processes of people involved in a conversational interaction. Research
      on how people process utterances while they are actually engaged in an
      interaction has been extremely rare. To that end, we have developed a
      conversational bot (computer program designed to mimic human communication) with
      which participants can chat in a format similar to instant messaging. This
      program allows for the recording of comprehension speed, and it can be interfaced
      with secondary tasks (e.g., lexical decisions) in order to examine online
      conversational processing. Additional research possibilities with this program
      are discussed.

PMID- 17552484
TI  - Controlling the e-mail mountain.

PMID- 17552485
TI  - Engaging clinicians in improving data quality in the NHS.

PMID- 17552486
TI  - National ETD, health records and clinical coding, a unique partnership.

PMID- 17552487
TI  - UKCHIP prepared by Pam Hughes.

PMID- 17552488
TI  - Professonalism and the work of the health informatics professional development
      board.

PMID- 17552489
TI  - New statistics on outpatients' care confirm millions of missed appointments.

PMID- 17552490
TI  - Coherently controlled ultrafast four-wave mixing spectroscopy.
AB  - A novel approach to coherent nonlinear optical spectroscopy based on two
      dimensional femtosecond pulse shaping is introduced. Multiple phase-stable output
      beams are created and overlapped at the sample in a phase-matched boxcars
      geometry via two-dimensional femtosecond pulse shaping. The pulse timing, shape,
      phase, and spectral content within all beams may be specified, yielding an
      unprecedented level of control over the interacting fields in nonlinear
      spectroscopic experiments. Heterodyne detection and phase cycling of the
      nonlinear signal are easily implemented due to the excellent phase stability
      among all output beams. This approach combines the waveform generation
      capabilities of magnetic resonance spectroscopy with the wavevector specification
      and phase matching of nonlinear optical spectroscopy, yielding the control
      capabilities and signal selectivity of both. Results on four prototype systems
      are used to illustrate some of the novel possibilities of this method.

PMID- 17552491
TI  - Role of sulfhydryl groups in transfection? A case study with chitosan-NAC
      nanoparticles.
AB  - This study investigated the use of chitosan-N-acetylcysteine (NAC) as a non-viral
      gene carrier. In particular, we aimed to elucidate whether the advantage of
      thiolation was more pronounced in the stabilization of particles or in the effect
      of nonspecific sulfhydryl reduction of the target cells. Low-viscosity chitosan
      was modified by covalent binding of NAC. The resulting conjugate displayed 1.35
      mM SH/g polymer. Particles produced via self-assembly of chitosan conjugate and
      pDNA had a mean particle size of 113.7 nm and a positive zeta-potential.
      Sulfhydryl group content on the particle surface was investigated by Ellman's
      test and papain reactivation assay, with the result of about 100 nM SH groups/mL
      nanoparticle suspension. An oxidation step was performed to stabilize polyplexes
      via disulfide bonds. The enhanced stability of oxidized particles against both
      polyanion heparin and alkaline pH was proven by a gel retardation assay. The
      stabilization was demonstrated to be reversible by treatment with glutathione.
      Further, the effect of immobilized SH groups and of supplementation with free NAC
      on transfection efficacy on Caco-2 cells was investigated. The expression of the
      transgene was raised 2.5-fold and 10-fold with nonoxidized thiomer polyplexes in
      comparison to polyplexes of unmodified chitosan and oxidized chitosan-NAC,
      respectively. The impact of sulfhydryl reduction on transfection was assessed via
      thiol group inactivation with 5,5'-dithiobis-(2-nitrobenzoic acid) (DNTB). This
      inactivation resulted in a decrease of transfection efficacy. In conclusion,
      chitosan-NAC conjugate was demonstrated to be beneficial for transfection, either
      for stabilization via disulfide bonds or for raising the expression of transgene
      via shifting the redox potential of the target cells.

PMID- 17552492
TI  - A novel conjugable translocator protein ligand labeled with a fluorescence dye
      for in vitro imaging.
AB  - A conjugable analogue of the benzodiazepine 4' '-chlorodiazepam (Ro5-4864), C6Ro5
      4864 was synthesized to probe the binding sites of translocator protein (18 kDa;
      TSPO), previously known as the peripheral benzodiazepine receptor for molecular
      imaging. The amino group in this analogue allows universal conjugation to
      signaling molecules. Lissamine-C6Ro5-4864, synthesized from C6Ro5-4864 and a
      lissamine fluorescence dye, was investigated in this study. This imaging agent
      exhibited micromolar binding affinity (Ki = 2.6 microM) to TSPO and was
      successfully imaged in TSPO rich glioma and breast cancer cell lines. These
      findings suggest that C6Ro5-4864 may provide opportunities in imaging disease
      states where TSPO levels are affected, such as cancer and neurologic diseases.

PMID- 17552493
TI  - Unbiasing scoring functions: a new normalization and rescoring strategy.
AB  - Ligand bias can contribute significantly to the number of false positives
      observed in a virtual screening campaign. Using a receptor-based docking approach
      against a well-established target of therapeutic importance, estrogen receptor
      alpha (ERalpha), coupled with several common scoring functions (ChemGuass,
      ChemGauss2, ChemScore, ScreenScore, ShapeGauss, and PLP), taken both individually
      and as a consensus, we sought to examine the characteristics of molecules
      retrieved by each. It has been previously shown that scoring functions (mainly
      empirical) exhibit bias in prioritizing more complicated molecules arising from
      additive components within the function. Using Spearmen's correlation
      coefficient, we show that a large set of descriptors calculated for a docked set
      of molecules exhibit positive correlation with the ranked position in a hitlist.
      Moreover, most of these descriptors correlate well with MW. To this end, rather
      than penalizing the docked score of all heavy molecular weight (MW) molecules and
      rewarding those of lower MW, as is common practice, we examine the impact of
      penalizing the score only of those molecules which were of higher MW, leaving
      lower MW molecules unaffected. Here, we introduce a new power function to aid the
      process. Using scoring frequency analysis and SIFt fingerprints, we acheived a
      more meaningful analysis of virtual screening (VS) performance than with
      enrichment calculations, facilitating target-specific VS method development.

PMID- 17552494
TI  - Flow injection amperometric detection of 2'-deoxyguanosine at a ruthenium oxide
      hexacyanoferrate modified electrode.
AB  - A ruthenium oxide hexacyanoferrate (RuOHCF) modified electrode was developed.
      Hydrodynamic voltammetry was employed to demonstrate the remarkable
      electrocatalytic activity toward the oxidation of 2'-deoxyguanosine. The RuOHCF
      modified electrode was used as amperometric detector for 2'-deoxyguanosine
      determination in a FIA apparatus. The influence of various experimental
      conditions was explored for optimum analytical performance, and at these
      experimental conditions, the method exhibited a linear response range to 2'
      deoxyguanosine extending from 3.8 to 252 micromol L(-1) with detection limit of
      94 nmol L(-1). Applications in DNA samples were examined, and the results for
      determination of 2'-deoxyguanosine were in good agreement with those obtained by
      HPLC analysis. Studies on the kinetics of the in vitro consumption of 2'
      deoxyguanosine by acetaldehyde were also performed.

PMID- 17552495
TI  - Suspension array with shape-coded silica nanotubes for multiplexed immunoassays.
AB  - A suspension array for multiplexed immunoassays has been developed using shape
      coded silica nanotubes (SNTs) as coding materials. Fabricated by multistep
      anodization template synthesis, each shape-coded SNT has several segments with
      different reflectance values depending on their diameters and wall thicknesses.
      Therefore, the code of each SNT can be "read-out" under a conventional optical
      microscope. The suspension array with shape-coded SNTs has shown high stability
      and dispersibility in aqueous buffer media and high detection sensitivity. The
      SNTs have not shown any visible degradation while submerged in aqueous solution
      for 7 months, the tubular structure and silanol groups on the inner and outer
      surfaces allow SNTs to disperse evenly in buffer solution, and the detection
      limit of an IgG protein is about 6 pM with 1.5 x 10(6) SNTs per mL. We have
      demonstrated the high selectivity of the SNTs suspension array for the detection
      of multianalytes in the multiplexed immunoassay experiments.

PMID- 17552496
TI  - Recovery of oligomers and cooperativity when monomers of the M2 muscarinic
      cholinergic receptor are reconstituted into phospholipid vesicles.
AB  - FLAG- and HA-tagged M2 muscarinic receptors from coinfected Sf9 cells have been
      purified in digitonin-cholate and reconstituted into phospholipid vesicles. The
      purified receptor was predominantly monomeric: it showed no detectable
      coimmunoprecipitation; it migrated as a monomer during electrophoresis before or
      after cross-linking with bis(sulfosuccinimidyl)suberate; and it bound agonists
      and antagonists in a manner indicative of identical and mutually independent
      sites. Receptor cross-linked after reconstitution or after reconstitution and
      subsequent solubilization in digitonin-cholate migrated almost exclusively as a
      tetramer. The binding properties of the reconstituted receptor mimicked those
      reported previously for cardiac muscarinic receptors. The apparent capacity for N
      [3H]methylscopolamine (NMS) was only 60% of that for [3H]quinuclidinylbenzilate
      (QNB), yet binding at saturating concentrations of [3H]QNB was inhibited fully
      and in a noncompetitive manner at comparatively low concentrations of unlabeled
      NMS. Reconstitution of the receptor with a saturating quantity of functional G
      proteins led to the appearance of three classes of sites for the agonist
      oxotremorine-M in assays with [3H]QNB; GMP-PNP caused an apparent interconversion
      from highest to lowest affinity and the concomitant emergence of a fourth class
      of intermediate affinity. All of the data can be described quantitatively in
      terms of cooperativity among four interacting sites, presumably within a
      tetramer; the effect of GMP-PNP can be accommodated as a shift in the
      distribution of tetramers between two states that differ in their cooperative
      properties. Monomers of the M2 receptor therefore can be assembled into tetramers
      with binding properties that closely resemble those of the muscarinic receptor in
      myocardial preparations.

PMID- 17552498
TI  - Femtosecond pump-probe transient absorption study of the photolysis of
      [Cp'Mo(CO)3]2 (Cp' = eta5-C5H4CH3): role of translational and rotational
      diffusion in the radical cage effect.
AB  - Femtosecond pump-probe studies of the photodissociation and subsequent radical
      cage pair recombination dynamics of the organometallic dimer [Cp'Mo(CO)3]2 (Cp' =
      eta5-C5H4CH3) are reported. The dynamics following photodissociation were studied
      in numerous noncoordinating hydrocarbon solvents. The results indicate that
      primary geminate recombination occurs on an ultrafast time scale (tau
      approximately 5 ps) and the efficiency of cage escape is inversely proportional
      to solvent viscosity. Investigation of the time-dependent anisotropy in this
      system allowed for an estimate of the rotational correlation time of the radical
      fragments (tau approximately 5-25 ps). Comparison of the rates of rotational
      motion with the population kinetics shows that the primary solvent cage dynamics
      and recombination efficiency are controlled by radical diffusion and not by
      radical rotation.

PMID- 17552497
TI  - Amino acid residues of Leishmania donovani cyclophilin key to interaction with
      its adenosine kinase: biological implications.
AB  - Cyclophilins (CyPs), by interacting with a variety of proteins, often modulate
      their biological activities and thus have been implicated in several cellular
      functions. However, mechanisms that determine such interactions are poorly
      understood. We earlier reported that an endoplasmic reticulum (ER)-located
      cyclophilin (LdCyP) from the purine auxotrophic parasitic protozoan Leishmania
      donovani reactivated its adenosine kinase (AdK). The AdK-reactivating property of
      LdCyP was however abolished at high ionic strength but not by nonionic
      detergents. Modeling of LdCyP, based on its crystal structure solved at 1.97 A
      resolution, revealed several solvent-exposed hydrophobic and charged residues.
      Mutagenesis of several of such solvent-exposed residues was performed and their
      corresponding activities with regard to their (i) AdK reactivation property, (ii)
      ability to form complex with the enzyme, (iii) capacity to induce red shift in
      the intrinsic tryptophan fluorescence maxima of AdK, and (iv) efficiency to
      withdraw the ADP inhibition from the AdK-mediated reaction were compared to the
      wild-type protein. Results indicated that while the replacement of R147 with
      either A or D severely impaired all of the above characteristics displayed by the
      wild-type LdCyP, the effect of mutating K114 and K153 was although relatively
      less but nevertheless noticeable. Alteration of other exposed hydrophobic and
      charged residues apparently did not have any discernible effect. Under the
      condition of cellular stress, the ER-located LdCyP is released into the cytoplasm
      with concomitant increase both in the specific activity of the cytosol-resident
      AdK and the uptake of radiolabeled Ado into the cells. These experiments, besides
      demonstrating the importance of the positive charge, identified R147 as the most
      crucial residue in the LdCyP-AdK interaction and provide evidence for the stress
      induced retrograde translocation of LdCyP from the ER to the cytoplasm. A
      possible implication of this interaction in the life cycle of the parasite is
      proposed.

PMID- 17552499
TI  - Self-interaction and strong correlation in DFTB.
AB  - The density functional based tight-binding (DFTB) method can benefit
      substantially from a number of developments in density functional theory (DFT)
      while also providing a simple analytical proving ground for new extensions. This
      contribution begins by demonstrating the variational nature of charge-self
      consistent DFTB (SCC-DFTB), proving the presence of a defined ground-state in
      this class of methods. Because the ground state of the SCC-DFTB method itself can
      be qualitatively incorrect for some systems, suitable forms of the recent LDA+U
      functionals for SCC-DFTB are also presented. This leads to both a new semilocal
      self-interaction correction scheme and a new physical argument for the choice of
      parameters in the LDA+U method. The locality of these corrections can only partly
      repair the HOMO-LUMO gap and chemical potential discontinuity, hence a novel
      method for introducing this further physics into the method is also presented,
      leading to exact derivative discontinuities in this theory at low computational
      cost. The prototypical system NiO is used as an illustration for these
      developments.

PMID- 17552500
TI  - Proton transfer in (HCOOH)2: an IR high-resolution spectroscopic study of the
      antisymmetric C-O stretch.
AB  - We report the fully analyzed high-resolution spectrum of the carboxylic acid
      dimer (HCOOH)2 in the gas phase. High-resolution IR spectra in the region of the
      antisymmetric C-O stretch vibration have been recorded at 1221.0-1226.7 cm(-1).
      The data could be fit within experimental uncertainty to a rigid rotor Watson S
      reduced Hamiltonian. The vibrational frequency of the C-O vibration is
      1225.3430(3) cm(-1). On the basis of the measurement of a tunneling splitting of
      0.0158(4)cm(-1) for the lower state and 0.0100(3) cm(-1) for the upper state, we
      determine a proton-transfer time of 1.0 and 1.7 ns for the ground and the
      vibrationally excited state, respectively.

PMID- 17552501
TI  - Triplet state excitation of alkali molecules on helium droplets: experiments and
      theory.
AB  - In this paper, we discuss the electronic structure of alkali dimer molecules in
      3Pig states on the surface of a helium droplet. The perturbation due to the
      droplet will in general not satisfy rotational symmetry around the internuclear
      axis of the diatom and thus, in addition to a broadening and blue shift, will
      cause a splitting of electronic levels that are degenerate in the free molecules.
      We propose a model based on general symmetry arguments and on a small number of
      physically reasonable parameters. We demonstrate that such a model accounts for
      the essential features of laser-induced fluorescence (LIF) and magnetic circular
      dichroism (MCD) spectra of the (1)3Pig-a3Sigma+ transition of Rb2 and K2.
      Furthermore the MCD spectra, analyzed according to the approach of Langford and
      Williamson [J. Phys. Chem. A 1998, 102, 2415], allow a determination of the
      populations of Zeeman sublevels in the ground state and thus a measurement of the
      surface temperature of the droplet. The latter agrees with the accepted
      temperature, 0.37 K, measured in the interior of a droplet.

PMID- 17552502
TI  - TD-DFT investigation of diarylethene dyes with cyclopentene, dihydrothiophene,
      and dihydropyrrole bridges.
AB  - We have investigated the visible spectra of closed-ring diarylethenes presenting
      cyclopentene, dihydrothiophene, and dihydropyrrole bridging structures. Our
      simulations have been performed with an ab initio time-dependent density
      functional theory approach that takes into account bulk environmental effects.
      The computed lambda(max) agree qualitatively with experiment, and once a simple
      statistical treatment is performed, a quantitative agreement is reached. Indeed,
      after linear fitting correction, the mean absolute error is limited to 6 nm or
      0.03 eV for the 57 diarylethenes considered. To unravel the most important
      parameters for this photochromic class, several structural parameters are
      correlated to the UV/vis spectra. It turns out that the bond length alternation
      in the chromogenic unit allows a fast and accurate prediction of the color of
      these dyes. In addition, we compare our results to available electrochemical
      data.

PMID- 17552503
TI  - Study of temperature effect on far-infrared spectra of liquid H2O and D2O by
      analytical theory and molecular dynamic simulations.
AB  - The results of a combined study of dielectric loss (epsilon"(nu)) and power
      absorption coefficient (alpha(nu)) are reported. The epsilon"(nu) and alpha(nu)
      values are obtained for liquid water (H2O) and heavy water (D2O) using analytical
      modeling and the molecular dynamics (MD) simulations method. The calculated
      spectra span the microwave and far-infrared (FIR) region. The temperature range
      probed is 220-355 K. Appropriate parametrization of the analytical model for
      liquid water enables the quantitative description of the dielectric spectra over
      the frequency range of 0-1000 cm-1. An excellent agreement between the calculated
      spectra and the experimental data demonstrates the accuracy of the applied
      analytical approximations. The spectra obtained using the MD simulations agree
      rather qualitatively with the experimental epsilon"(nu) and alpha(nu)
      dependences. The observed spectra are interpreted in terms of four molecular
      mechanisms that have been recently described [J. Phys. Chem. A 2006, 110, 9361].

PMID- 17552504
TI  - Toward improved syntheses of dendrimer-based magnetic resonance imaging contrast
      agents: new bifunctional diethylenetriaminepentaacetic acid ligands and
      nonaqueous conjugation chemistry.
AB  - Two different fourth-generation (G4) polyaminonamido dendrimer-based magnetic
      resonsance (MR) agents were prepared by a new synthetic approach wherein tert
      butyl-protected forms of 2-(4-isothiocyanatobenzyl)-6-methyldiethylenetriamine
      pentaacetic acid (1B4M-DTPA), bearing either an isothiocyanate or a succinimidyl
      ester moiety, respectively, were conjugated to the primary amines of the
      dendrimer. Purification was facilitated using a solid phase, N-(2
      aminoethyl)aminomethyl polystyrene. After Gd(III) incorporation, molar relaxivity
      measurements of both new dendrimer-based agents as compared to a G4 agent
      prepared by an aqueous chemistry route indicated no significant changes in
      relaxivity. Comparative MR imaging revealed equivalent enhancement of the vessels
      and organs such as the kidney and liver, although slightly different vascular
      clearance rates were observed. This general synthesis provides a procedure for
      preparation of dendrimer-based MR agents for clinical applications with higher
      yields and efficiency while enhancing versatility. The latter aspect is further
      demonstrated by preparation of a novel maleimide analog of 1B4M-DTPA from a key
      synthetic intermediate aniline derivative.

PMID- 17552505
TI  - Bidirectional, iterative approach to the structural delineation of the functional
      "chemoprint" in GPR40 for agonist recognition.
AB  - GPR40, free fatty acid receptor 1 (FFAR1), is a member of the GPCR superfamily
      and a possible target for the treatment of type 2 diabetes. In this work, we
      conducted a bidirectional iterative investigation, including computational
      modeling and site-directed mutagenesis, aimed at delineating amino acid residues
      forming the functional "chemoprint" of GPR40 for agonist recognition. The
      computational and experimental studies revolved around the recognition of the
      potent synthetic agonist GW9508. Our experimentally supported model suggested
      that H137(4.56), R183(5.39), N244(6.55), and R258(7.35) are directly involved in
      interactions with the ligand. We have proposed a polarized NH-pi interaction
      between H137(4.56) and GW9508 as one of the contributing forces leading to the
      high potency of GW9508. The modeling approach presented in this work provides a
      general strategy for the exploration of receptor-ligand interactions in G-protein
      coupled receptors beginning prior to acquisition of experimental data.

PMID- 17552506
TI  - Design, synthesis, and pharmacology of novel 7-substituted 3,4-dihydro-2H-1,2,4
      benzothiadiazine 1,1-dioxides as positive allosteric modulators of AMPA
      receptors.
AB  - A series of 3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxides have been
      synthesized and evaluated as potentiators of AMPA receptors. Attention was paid
      to the impact of the substituent introduced at the 7-position of the heterocycle.
      The biological evaluation was achieved by measuring the AMPA current in rat
      cortex mRNA-injected Xenopus oocytes. The most potent compound, 4-ethyl-7-fluoro
      3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxide (12a) was found to be active in
      an object recognition test in rats demonstrating cognition enhancing effects in
      vivo after oral administration.

PMID- 17552507
TI  - Synthesis and biological evaluation of 4(5)-(6-alkylpyridin-2-yl)imidazoles as
      transforming growth factor-beta type 1 receptor kinase inhibitors.
AB  - A series of 4(5)-(6-alkylpyridin-2-yl)imidazoles 13a-p, 17a, and 17b have been
      synthesized and evaluated for ALK5 inhibitory activity in an enzyme assay and in
      cell-based luciferase reporter assays. The quinoxalinyl analogue 13e inhibited
      ALK5 phosphorylation with an IC50 of 0.012 muM and showed more than 90%
      inhibition at 0.05 muM in a luciferase reporter assay using HaCaT cells
      transiently transfected with p3TP-luc reporter construct. The binding mode of 13e
      generated by flexible docking studies shows that 13e fits well into the active
      site cavity of ALK5 by forming several tight interactions.

PMID- 17552508
TI  - Design and synthesis of classical and nonclassical 6-arylthio-2,4-diamino-5
      ethylpyrrolo[2,3-d]pyrimidines as antifolates.
AB  - The classical antifolate N-{4-[(2,4-diamino-5-ethyl-7H-pyrrolo[2,3-d]pyrimidin-6
      yl)sulfanyl]benzoyl}-l-glutamic acid (2) and 15 nonclassical analogues (3-17)
      were synthesized as potential dihydrofolate reductase (DHFR) inhibitors and as
      antitumor agents. 5-Ethyl-7H-pyrrolo[2,3-d]pyrimidine-2,4-diamine (20) served as
      the key intermediate to which various aryl thiols and a heteroaryl thiol were
      appended at the 6-position via an oxidative addition reaction. The classical
      analogue 2 was synthesized by coupling the benzoic acid derivative 18 with
      diethyl l-glutamate followed by saponification. The classical compound 2 was an
      excellent inhibitor of human DHFR (IC50 = 66 nM) as well as a two digit nanomolar
      (<100 nM) inhibitor of the growth of several tumor cells in culture. Some of the
      nonclassical analogues were potent and selective inhibitors of DHFR from two
      pathogens (Toxoplasma gondii and Mycobacterium avium) that cause opportunistic
      infections in patients with compromised immune systems.

PMID- 17552509
TI  - Discovery of potent and muscle selective androgen receptor modulators through
      scaffold modifications.
AB  - A novel series of imidazolin-2-ones were designed and synthesized as highly
      potent, orally active and muscle selective androgen receptor modulators (SARMs),
      with most of the compounds exhibiting low nM in vitro potency in androgen
      receptor (AR) binding and functional assays. Once daily oral treatment with the
      lead compound 11a (AR Ki = 0.9 nM, EC50 = 1.8 nM) for 14 days induced muscle
      growth with an ED50 of 0.09 mg/kg, providing approximately 50-fold selectivity
      over prostate growth in an orchidectomized rat model. Pharmacokinetic studies in
      rats demonstrated that the lead compound 11a had oral bioavailability of 65% and
      a plasma half-life of 5.5 h. On the basis of their preclinical profiles, the
      SARMs in this series are expected to provide beneficial anabolic effects on
      muscle with minimal androgenic effects on prostate tissue.

PMID- 17552511
TI  - Molecular basis sets - a general similarity-based approach for representing
      chemical spaces.
AB  - A new method, based on generalized Fourier analysis, is described that utilizes
      the concept of "molecular basis sets" to represent chemical space within an
      abstract vector space. The basis vectors in this space are abstract molecular
      vectors. Inner products among the basis vectors are determined using an ansatz
      that associates molecular similarities between pairs of molecules with their
      corresponding inner products. Moreover, the fact that similarities between pairs
      of molecules are, in essentially all cases, nonzero implies that the abstract
      molecular basis vectors are nonorthogonal, but since the similarity of a molecule
      with itself is unity, the molecular vectors are normalized to unity. A symmetric
      orthogonalization procedure, which optimally preserves the character of the
      original set of molecular basis vectors, is used to construct appropriate
      orthonormal basis sets. Molecules can then be represented, in general, by sets of
      orthonormal "molecule-like" basis vectors within a proper Euclidean vector space.
      However, the dimension of the space can become quite large. Thus, the work
      presented here assesses the effect of basis set size on a number of properties
      including the average squared error and average norm of molecular vectors
      represented in the space-the results clearly show the expected reduction in
      average squared error and increase in average norm as the basis set size is
      increased. Several distance-based statistics are also considered. These include
      the distribution of distances and their differences with respect to basis sets of
      differing size and several comparative distance measures such as Spearman rank
      correlation and Kruscal stress. All of the measures show that, even though the
      dimension can be high, the chemical spaces they represent, nonetheless, behave in
      a well-controlled and reasonable manner. Other abstract vector spaces analogous
      to that described here can also be constructed providing that the appropriate
      inner products can be directly evaluated as is the case in this work, a problem
      that is well-known in kernel-based machine learning.

PMID- 17552510
TI  - Structure-based design of flavonoid compounds as a new class of small-molecule
      inhibitors of the anti-apoptotic Bcl-2 proteins.
AB  - Structure-based strategy was employed to design flavonoid compounds to mimic the
      Bim BH3 peptide as a new class of inhibitors of the anti-apoptotic Bcl-2
      proteins. The most potent compound, 4 (BI-33), binds to Bcl-2 and Mcl-1 with Ki
      values of 17 and 18 nM, respectively. Compound 4 inhibits cell growth in the MDA
      MB-231 breast cancer cell line with an IC50 value of 110 nM and effectively
      induces apoptosis.

PMID- 17552512
TI  - Synthesis and structural characterization of a series of lanthanide(II) amides:
      steric effect of amido ligand.
AB  - The synthesis and structures of a series of lanthanide(II) and lanthanide(III)
      complexes supported by the amido ligand N(SiMe3)Ar were described. Several
      lanthanide(III) amide chlorides were synthesized by a metathesis reaction of
      LnCl3 with lithium amide, including {[(C6H5)(Me3Si)N]2YbCl(THF)}2.PhCH3 (1),
      [(C6H3-iPr2-2,6)(SiMe3)N]2YbCl(mu-Cl)Li(THF)3.PhCH3 (4), [(C6H3-iPr2
      2,6)(SiMe3)N]YbCl2(THF)3 (6), and [(C6H3-iPr2-2,6)(SiMe3)N]2SmCl3Li2(THF)4 (7).
      The reduction reaction of 1 with Na-K alloy afforded bisamide ytterbium(II)
      complex [(C6H5)(Me3Si)N]2Yb(DME)2 (2). The same reaction for Sm gave an insoluble
      black powder. An analogous samarium(II) complex [(C6H5)(Me3Si)N]2Sm(DME)2 (3) was
      prepared by the metathesis reaction of SmI2 with NaN(C6H5)(SiMe3). The reduction
      reaction of ytterbium chloride 4 with Na-K alloy afforded monoamide chloride
      {[(C6H3-iPr2-2,6)(SiMe3)N]Yb(mu-Cl)(THF)2}2 (5), which is the first example of
      ytterbium(II) amide chloride, formed via the cleavage of the Yb-N bond. The same
      reduction reaction of 7 gave a normal bisamide complex [(C6H3-iPr2
      2,6)(SiMe3)N]2Sm(THF)2 (8) via Sm-Cl bond cleavage. This is the first example for
      the steric effect on the outcome of the reduction reaction in lanthanide(II)
      chemistry. 5 can also be synthesized by the Na/K alloy reduction reaction of 6.
      All of the complexes were fully characterized including X-ray diffraction for 1
      7.

PMID- 17552513
TI  - Identification of the radical anions of C2N4S2 and P2N4S2 rings by in situ EPR
      spectroelectrochemistry and DFT calculations.
AB  - The previously unknown radical anions of unsaturated E2N4S2 ring systems (E=RC,
      R2NC, R2P) can be generated voltammetrically by the one-electron reduction of the
      neutral species and, despite half-lives on the order of a few seconds, have been
      unambiguously characterized by electron paramagnetic resonance (EPR)
      spectroelectrochemistry using a highly sensitive in situ electrolysis cell.
      Cyclic voltammetric studies using a glassy-carbon working electrode in CH3CN and
      CH2Cl2 with [nBu4N][PF6] as the supporting electrolyte gave reversible formal
      potentials for the [E2N4S2]0/- process in the range of -1.25 to -1.77 V and
      irreversible peak potentials for oxidation in the range of 0.66 to 1.60 V (vs the
      Fc+/0 couple; Fc=ferrocene). Reduction of the neutral compound undergoes an
      electrochemically reversible one-electron transfer, followed by the decay of the
      anion to an unknown species via a first-order (chemical) reaction pathway. The
      values of the first-order rate constant, kf, for the decay of all the radical
      anions in CH2Cl2 have been estimated from the decay of the EPR signals for (X
      C6H4CN2S)2*-, where X=4-OCH3 (kf=0.04 s(-1)), 4-CH3 (kf=0.02 s(-1)), 4-H (kf=0.08
      s(-1)), 4-Cl (kf=0.05 s(-1)), 4-CF3 (kf=0.05 s(-1)), or 3-CF3 (kf=0.07 s(-1)),
      and for [(CH3)3CCN2S]2*- (kf=0.02 s(-1)), [(CH3)2NCN2S]2*- (kf=0.05 s(-1)), and
      [(C6H5)2PN2S]2*- (kf=0.7 s(-1)). Values of kf for X=4-H and for [(CH3)2NCN2S]2*-
      were also determined from the cyclic voltammetric responses (in CH2Cl2) and were
      both found to be 0.05 s(-1). Possible pathways for the first-order anion
      decomposition that are consistent with the experimental observations are
      discussed. Density functional theory calculations at the UB3LYP/6-31G(d) level of
      theory predict the structures of the radical anions as either planar (D2h) or
      folded (C2v) species; the calculated hyperfine coupling constants are in
      excellent agreement with experimental results. Linear correlations were observed
      between the voltammetrically determined potentials and both the orbital energies
      and Hammett coefficients for the neutral aryl-substituted rings.

PMID- 17552514
TI  - Synthesis of a Mn6 cluster and its self-assembly of an azido-bridged polymer.
AB  - A rare micro6-oxo-centered Mn6 mixed-valent cluster (1) is prepared and used as a
      secondary building unit for the self-assembly of its azido-bridged polymeric
      analogue (2) in a systematic way with the retention of the Mn6 core of 1. Both
      complexes are characterized by X-ray single-crystal structure determination. The
      complex 1 was crystallized in a monoclinic system, space group P21, a=11.252(5)
      A, b=20.893(9) A, c=12.301(6) A, and beta=115.853(7) degrees, whereas the
      polymeric analogue 2 was crystallized in an orthorhombic system, space group
      P212121, a=13.1941(8) A, b=14.9897(9) A, and c=27.8746(14) A. Variable
      temperature magnetic behavior showed the presence of strong antiferromagnetic
      interaction in both cases.

PMID- 17552515
TI  - Linear trinuclear mixed-metal Co(II)-Gd(III)-Co(II) single-molecule magnet:
      [L(2)Co(2)Gd][NO(3)] x 2CHCl(3) (LH(3) = (S)P[N(Me)N=CH-C(6)H(3)-2-OH-3-OMe](3)).
AB  - A linear trinuclear mixed-metal Co(2)Gd complex supported by two phosphorus-based
      multisite coordination ligands has been shown to be a single-molecule magnet.

PMID- 17552516
TI  - First isolation and kinetic study of hypervalent 10-As-5 organoarsenic compounds
      with a C-apical, O-equatorial configuration.
AB  - Hypervalent organoarsenic compounds violating the apicophilicity concept were
      isolated for the first time, and the energy of isomerization of these arsoranes
      to the more stable stereoisomers appeared to be lower than that of the phosphorus
      analogues based on the kinetic studies.

PMID- 17552517
TI  - Elastic and inelastic electron tunneling spectroscopy of a new rectifying
      monolayer.
AB  - Rectification of electrical current was observed in a Langmuir-Schaefer monolayer
      of fullerene-bis[ethylthio-tetrakis(3,4-dibutyl-2-thiophene-5-ethenyl)-5-bromo
      3,4-dibutyl-2-thiophene] malonate, Au electrodes at room temperature (there are
      two regimes of asymmetry, at lower bias, i.e., between 0 and +/-2 V, and at
      higher bias), and also between Pb and Al electrodes at 4.2 K. The latter
      experiment was coupled with second harmonic detection of the second derivative of
      the current with respect to voltage (d2I/dV2). The d2I/dV2 spectrum shows
      intramolecular vibrations, and also two antisymmetric broad bands, centered at +/
      0.65 V, due to resonant electron tunneling between the Fermi level(s) of the
      electrodes and the lowest unoccupied molecular orbital of the molecule.

PMID- 17552519
TI  - Oriented growth of the metal organic framework Cu(3)(BTC)(2)(H(2)O)(3).xH(2)O
      tunable with functionalized self-assembled monolayers.

PMID- 17552518
TI  - Structure-based design leads to the identification of lithium mimetics that block
      mania-like effects in rodents. possible new GSK-3beta therapies for bipolar
      disorders.
AB  - More than two million American adults, or approximately one percent of the
      population 18 years or older, suffer from bipolar disorder. Current treatments
      include the so-called "mood stabilizers," lithium and valproic acid. Both are
      relatively dated drugs that are only partially effective and produce various
      undesirable side effects including weight gain. Based upon continued efforts to
      understand the molecular target for lithium, it now appears that specific
      inhibitors of the enzyme glycogen synthase kinase-3beta (GSK-3beta) may mimic the
      therapeutic action of mood stabilizers and might therefore allow for the design
      of improved drugs for treating patients with bipolar disorder as well as certain
      neurodegenerative disorders. Furthermore, the pro-apoptotic properties of the GSK
      3 enzyme suggest the possible use of such inhibitors as neuroprotective agents.
      In fact, neuroprotection may contribute to the treatment of mood disorders. The
      present chemistry, modeling, and biology efforts have identified 3-benzofuranyl-4
      indolylmaleimides as potent and relatively selective GSK-3beta inhibitors. The
      best ligand in this series (having a Ki value of 4.6 nM against GSK-3beta) was
      studied in a novel mouse model of mania that has recently been validated with
      several clinically effective mood stabilizers. This study presents the first
      demonstration of the efficacy of a GSK-3beta inhibitor in this mouse model of
      mania. Selective brain penetrable GSK-3 ligands like those described herein
      become valuable research tools in better defining the role of this multifaceted
      kinase in both physiological and pathophysiological events.

PMID- 17552520
TI  - Catalase and epoxidation activity of manganese salen complexes bearing two
      xanthene scaffolds.
AB  - A series of manganese Hangman salen ligand platforms functionalized by tert-butyl
      groups in the 3 and 3' positions using the Suzuki cross-coupling methodology are
      presented. The Hangman platforms support multielectron chemistry mediated by
      proton-coupled electron transfer (PCET), as demonstrated by their ability to
      promote the catalytic disproportionation of hydrogen peroxide to oxygen and water
      via a high-valent metal oxo. The addition of the steric groups to the salen
      macrocycle leads to enhanced catalase activity by circumventing side reactions
      that sequester the catalyst off pathway. The stereochemistry imposed by the
      cyclohexanediamine backbone of the salen platform is revealed by the epoxidation
      of 1,2-dihydronapthalene by a variety of oxidants. Improved enantiomeric excess
      and catalase activity as compared to sterically unmodified counterparts
      establishes the efficacy of the tert-butyl groups in promoting PCET catalysis on
      the Hangman platform.

PMID- 17552521
TI  - Aluminosilicate surfaces as promoters for peptide bond formation: an assessment
      of Bernal's hypothesis by ab initio methods.
AB  - The role in prebiotic chemistry that Bronsted and Lewis sites, both present at
      the surface of common aluminosilicates, may have played in favoring the peptide
      bond formation has been addressed by ab initio methods within a cluster approach.
      B3LYP/6-31+G(d,p) free energy potential energy surfaces have been fully
      characterized for the model reaction glycine + NH3 --> 2-NH2 acetamide (mimicking
      the true 2 Gly --> GlyGly one) occurring on (i) a Lewis site, (ii) a Bronsted
      site, and (iii) a combined action of Lewis/Bronsted sites. Compared to the gas
      phase (gp) activation free energy of 50 kcal/mol, the Lewis site alone reduces
      the gp barrier to 41 kcal/mol, whereas the activation by the Bronsted site
      dramatically reduces the barrier to about 18 kcal/mol. Nevertheless, formation of
      the prereactant complex in this latter case will rarely occur, since water will
      easily displace the glycine molecule interacting with the Bronsted site. However,
      if a realistic feldspar surface with neighboring Bronsted and Lewis sites is
      considered, the proper prereactant complex is highly stabilized by a simultaneous
      interaction with the Lewis and the Bronsted sites, in such a way that the Lewis
      site strongly attaches the glycine molecule to the surface whereas the Bronsted
      site efficiently catalyzes the condensation reaction, showing that the interplay
      between Lewis/Bronsted sites is an important issue. The free energy barrier
      computed for the realistic feldspar surface model is 26 kcal/mol. The role of
      dispersive interactions on the free energy barrier and the stabilization of the
      final product, not accounted for by the B3LYP functional, have been estimated and
      shown to be substantial. Speculations about further elongation of the formed
      dipeptide have been put forward on the basis of the relatively strong interaction
      energy of the formed GlyGly dipeptide with the aluminosilicate surface.

PMID- 17552522
TI  - Influence of stereochemistry and redox potentials on the single- and double
      strand DNA cleavage efficiency of Cu(II) and Ni(II) Lys-Gly-His-derived ATCUN
      metallopeptides.
AB  - The DNA cleavage chemistry of a series of metallopeptides based on the amino
      terminal Cu and Ni (ATCUN) binding motif of proteins has been studied.
      Specifically, the impact of the positioning of charged Lys side chains and their
      stereochemistry on metal reduction potentials and DNA cleavage reactivity have
      been quantitatively evaluated. Both Cu and Ni metallopeptides show a general
      increase in reactivity toward DNA with an increasing number of Lys residues,
      while a corresponding decrease in complex reduction potential reflects the
      enhanced sigma-donor character of the Lys side chain relative to that of Gly.
      Placement of Lys at the first position in the tripeptide ligand sequence resulted
      in a greater increase in DNA cleavage reactivity, relative to placement at the
      second position, while a switch from an l-Lys to a d-Lys typically resulted in
      enhanced reactivity, as well as perturbations of reduction potential. In the case
      of Cu peptides, reactivity was enhanced with both increasing positive charge
      density on the peptide and stabilization of the Cu3+ state. However, for Ni
      peptides, while the general trends are the same, the correlation with redox
      behavior was less pronounced. Most likely these differences in specific trends
      for the Cu and Ni complexes reflect the distinct coordination preferences for
      Cu3+/2+ and Ni3+/2+ oxidation states, and the consequent distinct positioning of
      metal-associated reactive oxygen species, as well as the orientation of the DNA
      associated complex. Thus, the amino acid composition and stereochemistry of ATCUN
      metallopeptides can tune the intrinsic reactivities of these systems (their
      ability to promote formation and activity of metal-associated ROS) as well as
      their overall structural features, and both of these aspects appear to influence
      their reactivity and efficiency of DNA strand scission.

PMID- 17552523
TI  - Barriers to ion translocation in cationic and anionic receptors from the Cys-loop
      family.
AB  - Understanding the mechanisms of gating and ion permeation in biological channels
      and receptors has been a long-standing challenge in biophysics. Recent advances
      in structural biology have revealed the architecture of a number of transmembrane
      channels and allowed detailed, molecular-level insight into these systems.
      Herein, we have examined the barriers to ion conductance and origins of ion
      selectivity in models of the cationic human alpha7 nicotinic acetylcholine
      receptor (nAChR) and the anionic alpha1 glycine receptor (GlyR), based on the
      structure of Torpedo nAChR. Molecular dynamics simulations were used to determine
      water density profiles along the channel length, and they established that both
      receptor pores were fully hydrated. The very low water density in the middle of
      the nAChR pore indicated the existence of a hydrophobic constriction. By
      contrast, the pore of GlyR was lined with hydrophilic residues and remained well
      hydrated throughout. Adaptive biasing force simulations allowed us to reconstruct
      potentials of mean force (PMFs) for chloride and sodium ions in the two
      receptors. For the nicotinic receptor we observed barriers to ion translocation
      associated with rings of hydrophobic residues-Val13' and Leu9'-in the middle of
      the transmembrane domain. This finding further substantiates the hydrophobic
      gating hypothesis for nAChR. The PMF revealed no significant hydrophobic barrier
      for chloride translocation in GlyR. For both receptors nonpermeant ions displayed
      considerable barriers. Thus, the overall electrostatics and the presence of rings
      of charged residues at the entrance and exit of the channels were sufficient to
      explain the experimentally observed anion and cation selectivity.

PMID- 17552524
TI  - Five- and six-membered conformationally locked 2',4'-carbocyclic ribo-thymidines:
      synthesis, structure, and biochemical studies.
AB  - Two unusual reactions involving the 5-hexenyl or the 6-heptenyl radical
      cyclization of a distant double bond at C4' and the radical center at C2' of the
      ribofuranose ring of thymidine have been used as key steps to synthesize North
      type conformationally constrained cis-fused bicyclic five-membered and six
      membered carbocyclic analogues of LNA (carbocyclic-LNA-T) and ENA (carbocyclic
      ENA-T) in high yields. Their structures have been confirmed unambiguously by long
      range 1H-13C NMR correlation (HMBC), TOCSY, COSY, and NOE experiments. The
      carbocyclic-LNA-T and carbocyclic-ENA-T were subsequently incorporated into the
      antisense oligonucleotides (AONs) to show that they enhance the Tm of the
      modified AON/RNA heteroduplexes by 3.5-5 degrees C and 1.5 degrees C/modification
      for carbocyclic-LNA-T and carbocyclic-ENA-T, respectively. Whereas the relative
      RNase H cleavage rates with carbocyclic-LNA-T, carbocyclic-ENA-T, aza-ENA-T, and
      LNA-T modified AON/RNA duplexes were found to be very similar to that of the
      native counterpart, irrespective of the type and the site modification in the AON
      strand, a single incorporation of carbocyclic-LNA and carbocyclic-ENA into AONs
      leads to very much more enhanced nuclease stability in the blood serum (stable
      >48 h) as compared to that of the native (fully degraded <3 h) and the LNA
      modified AONs (fully degraded <9 h) and aza-ENA ( approximately 85% stable in 48
      h). Clearly, remarkably enhanced lifetimes of these carbocyclic-modified AONs in
      the blood serum may produce the highly desired pharmacokinetic properties because
      of their unique stability and consequently a net reduction of the required
      dosage. This unique quality as well as their efficient use as the AON in the
      RNase H-promoted cleavage of the target RNA makes our carbocyclic-LNA and
      carbocyclic-ENA modifications excellent candidates as potential antisense
      therapeutic agents.

PMID- 17552525
TI  - Switching off and on the supramolecular chiral memory in porphyrin assemblies.

PMID- 17552526
TI  - Quantum yield heterogeneities of aqueous single-wall carbon nanotube suspensions.

PMID- 17552527
TI  - Organocatalysis in conjugate amine additions: synthesis of beta-amino acid
      derivatives.

PMID- 17552528
TI  - Electrochemiluminescence of zeolite-encapsulated poly(p-phenylenevinylene).

PMID- 17552529
TI  - Janus microgels prepared by surfactant-free pickering emulsion-based modification
      and their self-assembly.

PMID- 17552530
TI  - Synthesis and characterization of a new red-emitting Ca2+ indicator, calcium
      ruby.
AB  - Calcium Ruby m-Cl (X = H, Y = Cl) is a visible-light excited red-emitting calcium
      concentration ([Ca2+]) indicator dye (579/598 nm peak excitation/emission) with a
      side arm for conjugation via EDC or click chemistry. Its large molar extinction
      and high quantum yield rank it among the brightest long-wavelength Ca2+
      indicators. Calcium Ruby is a promising alternative to existing dyes for imaging
      [Ca2+] in multicolor fluorescence applications or in the presence of yellow-green
      cellular autofluorescence.

PMID- 17552531
TI  - Enantioselective synthesis of trifluoromethyl-substituted cyclopropanes.
AB  - The reaction of 1-aryl-2,2,2-trifluorodiazoethanes with alkenes, catalyzed by the
      adamantylglycine-derived dirhodium complex Rh2(R-PTAD)4, generates
      trifluoromethyl-substituted cyclopropanes with high diastereoselectivity (>94%)
      and enantioselectivity (88->98%).

PMID- 17552532
TI  - Synthesis and RNA binding selectivity of oligonucleotides modified with five-atom
      thioacetamido nucleic acid backbone structures.
AB  - Convenient chemical synthesis and incorporation of dithymidine and thymidine
      cytidine dimer blocks connected with a five-atom amide linker N3'-CO-CH2-S-CH2
      into oligonucleotides (ONs) are reported. The UV-Tm experiments for binding
      affinities of these mixed backbone ONs with complementary DNA and RNA sequences
      revealed important results such as significantly higher RNA-binding selectivity
      as compared with complementary DNA. NMR studies of the dimer blocks suggested a
      marginal increase in the N-type sugar conformations over that of the native DNA.

PMID- 17552533
TI  - Template-controlled face-to-face stacking of olefinic and aromatic carboxylic
      acids in the solid state.
AB  - A rigid 1,8-dipyridylnaphthalene template for supramolecular organization of
      unsaturated dicarboxylic acids in the solid state has been developed. Self
      assembly of the template and aromatic dicarboxylic acids generates nondistorted
      paracyclophane and pyridinophane architectures with perfectly superimposed pi
      systems. The dipyridyl template can be used to promote stereoselective solid
      state dimerization of olefinic dicarboxylic acids.

PMID- 17552534
TI  - Efficient nucleophilic aromatic substitution between aryl nitrofluorides and
      alkynes.
AB  - The nucleophilic aromatic substitution reaction between electron-deficient aryl
      fluorides and terminal alkynes is shown to be efficiently promoted by sodium
      bis(trimethylsilyl)amide as a base. Moderate to excellent yields of 2
      ethynylnitrobenzene products can be obtained under mild conditions.

PMID- 17552535
TI  - PLUS: a regional groundwater assessment and ranking tool.
AB  - There has been interest within the pesticide regulatory community in developing a
      tool that can provide estimates of potential pesticide exposure in shallow
      groundwater across an intended use area. Therefore, industry initiated an
      investigative project based on the PRZM 3.12 model, which uses regional soils and
      weather in an easy to use interface. The goal of this proof-of-concept is to
      facilitate the refinement of groundwater exposure estimates. The focus of this
      paper is to report the effectiveness of the tool as a regional estimator of
      potential groundwater contamination.

PMID- 17552536
TI  - Relative stability of formamidine and carbamate groups in the bifunctional
      pesticide formetanate hydrochloride.
AB  - Formetanate hydrochloride is a bifunctional pesticide with remarkable solubility,
      high toxicity, and potential mobility in aqueous environments. The relative
      stability of the formamidine and carbamate groups in this compound can be used to
      predict the identity of its degradation products in water. The reported NMR and
      UV-vis spectroscopic studies revealed that the formamidine group is more labile
      than the carbamate group under strongly basic conditions, as well as under
      predetermined field conditions. The half-life of the formamidine group was
      determined to be 3.9 h under strongly basic conditions (pH 12.6) and 14.4 h under
      mildly basic conditions (pH 7.6). The longevity of the carbamate group may exceed
      6 months due its resistance to base-promoted degradation. These results may be
      used in the design of more specific remediation technology for formetanate
      contaminated surface water.

PMID- 17552537
TI  - Influence of rainfall distribution on simulations of atrazine, metolachlor, and
      isoxaflutole/metabolite transport in subsurface drained fields.
AB  - This research investigated the impact of modeling atrazine, metolachlor, and
      isoxaflutole/metabolite transport in artificially subsurface drained sites with
      temporally discrete rainfall data. Differences in considering rainfall
      distribution are unknown in regard to estimating agrochemical fluxes in the
      subsurface. The Root Zone Water Quality Model (RZWQM) simulated pesticide fate
      and transport at three subsurface drained sites: metolachlor/atrazine field
      experiment in Baton Rouge, LA (1987), and two isoxaflutole/metabolite field
      experiments in Allen County and Owen County, Indiana (2000). The modeling assumed
      linear, equilibrium sorption based on average reported physicochemical and
      environmental fate properties. Assumed rainfall intensity and duration influenced
      transport by runoff more than transport by subsurface drainage. As the importance
      of macropore flow increased, the necessity for using temporally discrete rainfall
      data became more critical. Long-term simulations indicated no significant
      difference between average or upper percentile (i.e., <2% difference in percent
      loss as a function of mass applied) atrazine, metolachlor, or
      isoxaflutole/metabolite loss through subsurface drainage among the three
      different rainfall assumptions. It was necessary (i.e., within 7% of predicted
      loss) to use hourly or average duration storm events as opposed to daily rainfall
      data for total (i.e., runoff and subsurface drainage) pesticide loss over the
      long term.

PMID- 17552538
TI  - Isolation and characterization of bacteria capable of degrading polycyclic
      aromatic hydrocarbons (PAHs) and organophosphorus pesticides from PAH
      contaminated soil in Hilo, Hawaii.
AB  - Nineteen bacterial strains were isolated from petroleum-contaminated soil in
      Hilo, HI, and characterized by two different spray-plated methods, turbidity test
      in liquid medium, and 16S rRNA gene sequence analysis. Analysis of the soil
      showed 13 polycyclic aromatic hydrocarbons (PAHs) in a range from 0.6 to 30 mg/kg
      of dry weight each and 12 PAH metabolites. Five distinct bacterial strains (C3,
      C4, P1-1, JS14, and JS19b1) selected from preliminary plating and turbidity tests
      were further tested for PAH degradation through single PAH degradation assay.
      Strains C3, C4, and P1-1 degraded phenanthrene (40 mg/L) completely during 7 days
      of incubation. Strain JS14 degraded fluoranthene (40 mg/L) completely during 10
      days of incubation. Strain JS19b1 degraded 100% of phenanthrene (40 mg/L) in 7
      days, 77% of fluorene (40 mg/L) in 14 days, 97% of fluoranthene (40 mg/L) in 10
      days, and 100% of pyrene (40 mg/L) in 14 days. Turbidity tests showed that
      strains P1-1, JS14, and JS19b1 utilized several organophosphorus pesticides as
      growth substrate. P1-1 can degrade carbofenothion, chlorfenvinphos, diazinon,
      fonofos, and pirimiphos-methyl. JS14 can transform chlorfenvinphos and diazinon.
      JS19b1 can break down diazinon, pirimiphos-methyl, and temephos.

PMID- 17552539
TI  - Advances in pesticide environmental fate and exposure assessments.
AB  - Globalization of markets and the growing world population increase threats of
      invasive and exotic species and place greater demands on food and fiber
      production. Pest management in both agricultural and nonagricultural settings
      employs established practices and new biological, chemical, and management
      technologies. Pesticides are an essential tool in integrated pest management.
      Without pesticides a significant percentage of food and fiber crops would be
      lost, infectious diseases would increase, and valuable native habitats would be
      devastated. Therefore, it is important to understand the environmental fate of
      pesticides and assess their potential exposure and associated risks to human
      health and the environment. This paper summarizes the Advances in Pesticide
      Environmental Fate and Exposure Assessment symposium held at the 231st National
      Meeting of the American Chemical Society (Atlanta, GA, 2006). The focus of the
      symposium was to provide current information on advances in pesticide
      environmental fate and exposure assessments. Thirty papers were presented on
      advances ranging from subcellular processes to watershed-scale studies on topics
      including chemical degradation, sorption, and transport; improved methodologies;
      use of modeling and predictive tools; exposure assessment; and treatment and
      remediation. This information is necessary to develop more effective pesticide
      use and management practices, to better understand pesticide fate and associated
      exposures and risks, to develop mitigation and remediation strategies, and to
      establish sound science-based regulations.

PMID- 17552540
TI  - Temperature and pH effect on the microbial reductive transformation of
      pentachloronitrobenzene.
AB  - The effect of pH and temperature on the microbial reductive transformation of
      pentachloronitrobenzene (PCNB), an organochlorine fungicide, was investigated
      with a mixed fermentative/methanogenic culture developed from a contaminated
      estuarine sediment. Culture series were incubated at a temperature range from 4
      to 45 degrees C at pH 6.9+/-0.1 and at a pH range from 2.7+/-0.1 to 7.6+/-0.1 at
      22 degrees C. Significant differences were observed in terms of biotransformation
      rate, extent, and products as a function of temperature. Incubation at different
      pH values resulted in differences in biotransformation rate and extent, but not
      in terms of products formed. PCNB (3 microM) was transformed to
      pentachloroaniline (PCA) in all culture series. However, sequential
      dechlorination of PCA was observed only at a temperature range from 4 to 35
      degrees C and at a pH range from 6.2+/-0.1 to 7.6+/-0.1. The highest PCA
      dechlorination rate was observed at 22 degrees C and at pH 7.6+/-0.1. The effect
      of temperature on the PCA dechlorination rate was modeled using an Arrhenius
      relationship, which accounts for both enzyme activation and deactivation. The
      dechlorination of PCA and chlorinated aniline intermediates was simulated using a
      branched-chain Michaelis-Menten model, and kinetic constants were determined.

PMID- 17552541
TI  - Occurrence of naturally acetylated lignin units.
AB  - This work examines the occurrence of native acetylated lignin in a large set of
      vascular plants, including both angiosperms and gymnosperms, by a modification of
      the so-called Derivatization Followed by Reductive Cleavage (DFRC) method.
      Acetylated lignin units were found in the milled wood lignins of all angiosperms
      selected for this study, including mono- and eudicotyledons, but were absent in
      the gymnosperms analyzed. In some plants (e.g., abaca, sisal, kenaf, or
      hornbeam), lignin acetylation occurred at a very high extent, exceeding 45% of
      the uncondensed (alkyl-aryl ether linked) syringyl lignin units. Acetylation was
      observed exclusively at the gamma-carbon of the lignin side chain and
      predominantly on syringyl units, although a predominance of acetylated guaiacyl
      over syringyl units was observed in some plants. In all cases, acetylation
      appears to occur at the monomer stage, and sinapyl and coniferyl acetates seem to
      behave as real lignin monomers participating in lignification.

PMID- 17552542
TI  - Effects of soluble tea polysaccharides on hyperglycemia in alloxan-diabetic mice.
AB  - The effects of tea water extracts (TWE), crude tea polysaccharides (CTP), and a
      tea polysaccharide fraction (TPF) were tested on hyperglycemic diabetic mice.
      Results indicated that TWE, CTP, and TPF could significantly decrease fasting
      blood glucose (FBG) and glucosylated serum protein (GSP) in alloxan-induced
      diabetic mice compared to the control group. In vitro antioxidant activities of
      TWE, CTP, and TPF for scavenging hydroxyl radicals and superoxide radicals
      decreased with the degree of purification and were lowest for TPF. High
      performance gel permeation chromatography (HPGPC) and component analysis revealed
      the molecular mass distribution and constituents of TWE, CTP, and TPF, indicating
      that a 100-120 kDa fraction contained the hypoglycemic activity. This fraction
      was essentially composed of polysaccharides (approximately 90%) with substantial
      amounts of arabinogalactan proteins. The second-derivative IR spectra of TWE,
      CTP, and TPF with peak intensity around 1075 and 1045 cm(-1), which characterize
      galactopyranose in the backbone and arabinofuranose units in side branches,
      respectively, further substantiated the importance of the arabinogalactan
      proteins. Taken together, the results indicate that a soluble tea polysaccharide
      is the major hypoglycemic factor in tea and that this polysaccharide may be
      developed to a potential natural hypoglycemic functional ingredient.

PMID- 17552543
TI  - Stability of the Clostridium botulinum type A neurotoxin complex: an empirical
      phase diagram based approach.
AB  - Clostridium botulinum type A neurotoxin (BoNT/A complex) is of great interest to
      the pharmaceutical industry. The drug itself is a natural complex of the toxin
      and a number of associated proteins. Surprisingly, relatively little is known
      about the exact structure and stability of the 900 kDa BoNT/A complex and its
      component proteins with the exception of the 150 kDa neurotoxin. In this study we
      describe the relative stability of the BoNT/A complex, the neurotoxin, and its
      associated proteins over a wide range of temperature and pH employing circular
      dichroism, intrinsic and 8-anilino-1-naphthalene sulfonate (ANS) fluorescence,
      and static light scattering. The data suggest a strong stabilizing effect of the
      associated proteins on the neurotoxin component. This data is compiled into
      empirical phase diagrams which permit the simultaneous visualization of multiple
      data sets over a wide range of conditions.

PMID- 17552545
TI  - Interfacial friction and adhesion of cross-linked polymer thin films swollen with
      linear chains.
AB  - The preparation and interfacial properties of a new type of tethered, thin-film
      lubricant coating are presented. These coatings are composed of three components:
      a dense self-assembled monolayer (SAM) underlayer that presents reactive vinyl
      groups at its surface; a cross-linked polydimethylsiloxane (PDMS) overlayer that
      is covalently tethered to the SAM; and free, mobile linear PDMS chains dispersed
      in the network. We investigate the influence of the molecular weight (Ms) and
      concentration of the free PDMS chains on the structure and equilibrium swelling
      properties of the cross-linked films. Using a bead-probe lateral force microscopy
      measurement technique, we also quantify the interfacial friction and adhesion
      characteristics of surfaces functionalized with these coatings. We find that both
      the volume fraction and the molecular weight of free PDMS molecules in the
      coatings influence their interfacial friction and adhesion properties. For
      example, the addition of short PDMS chains in dry, cross-linked PDMS thin films
      yields tethered surface coatings with ultralow friction coefficients (mu = 5.2 x
      10(-3)). An analysis based on classical lubrication theory suggests that the
      reduction in friction force produced by free polymer is a consequence of the
      gradual separation of asperities on opposing surfaces and the consequent
      substitution of solid-solid friction by viscous drag of the free polymer chains
      in the network.

PMID- 17552544
TI  - High-quality ZnS shells for CdSe nanoparticles: rapid microwave synthesis.
AB  - Using a domestic microwave oven and new, inexpensive precursors, a rapid and
      reliable synthesis of highly luminescent CdSe/ZnS NPs was developed. To evaluate
      the quality of our core/shell particles for varying shell thickness in comparison
      to that of CdSe/ZnS nanoparticles obtained commercially, the parameter
      fluorescence quantum yield is been used as well as a new, straightforward,
      thiophenol-based shell-quality test as a tool to ensure a dense ZnS shell without
      holes and cracks, which is a prerequisite for high luminescence and stability.

PMID- 17552546
TI  - Controlled assembly of micrometer-sized spheres: theory and application.
AB  - Site-selective assembly of 5 microm amine-functionalized glass spheres from
      aqueous suspensions onto gold surfaces patterned with carboxylic acid and methyl
      terminated thiols has been achieved through the introduction of a variable tilt
      flow cell. In situ microscope imaging has been employed to study the four phases
      of assembly independently, and the relative roles of electrostatic attraction and
      capillary emersion have been explored. In contradiction to the commonly
      recognized electrostatic assembly model, detailed theoretical analysis and
      experimental evidence are presented to support a mechanism where patterning
      occurs at the point of meniscus contact. Control of pattern quality is
      demonstrated through the comparison of results obtained from a variety of
      experiments, and the best conditions for the assembly of monolayer features are
      identified. Finally, evidence for the extension of this assembly method to the
      production of singlet sphere arrays is discussed.

PMID- 17552547
TI  - Preparation of DNA-silver nanohybrids in multilayer nanoreactors by in situ
      electrochemical reduction, characterization, and application.
AB  - Novel nanocomposite films containing DNA-silver nanohybrids have been
      successfully fabricated by combined use of the layer-by-layer self-assembly
      technique and an in situ electrochemical reduction method with the DNA-Ag+
      complex as one of the building blocks. UV-vis absorption spectroscopy was
      employed to monitor the buildup of the multilayer films, which suggested a
      progressive deposition with almost an equal amount of the DNA-Ag+ complex in each
      cycle. The following electrochemical reduction of silver resulted in the
      formation of metal nanoparticles in the film, which was evidenced by the
      evolution of the intense plasmon absorption band originating from silver.
      Scanning electron microscopy indicated that the particles formed in the
      multilayer films possessed good monodispersity and stability, thanks to the
      surrounding polymers. X-ray photoelectron spectroscopy further confirmed the
      presence of the main components (such as DNA and metallic silver) of the
      nanocomposite films. In addition, we show that the size of the metal
      nanoparticles and the optical property of the film could be readily tuned by
      manipulating the assembly conditions. Furthermore, the feasibility of the as
      prepared nanocomposite films functioning as a surface-enhanced Raman scattering
      active substrate for sensing purposes was investigated, and the results showed
      great enhancement of the Raman signal of two probe molecules, Rhodamine 6G and 4
      aminothiophenol.

PMID- 17552548
TI  - Interfacial ion pairing at the interface between water and a room-temperature
      ionic liquid, N-tetradecylisoquinolinium bis(pentafluoroethylsulfonyl)imide.
AB  - The specific interaction of N-tetradecylisoquinolinium (C(14)Iq+) with Cl- and Br
      has been detected in the voltammetry of ion transfer and electrocapillarity at
      the interface between an aqueous solution (W) and a room-temperature ionic liquid
      (RTIL), N-tetradecylisoquinolinium bis(pentafluoroethylsulfonyl)imide
      ([C(14)Iq+][C(2)C(2)N-]). This specific interaction also makes the transfer of Cl
      and Br- into [C(14)Iq+][C(2)C(2)N-] energetically more favorable in comparison
      with that of F- and SO(4)(2-). The width of the polarized potential window in ion
      transfer voltammetry at the [C(14)Iq+][C(2)C(2)N-]|W interface is significantly
      narrower because of the transfer of anions from W to RTIL. The degree of affinity
      of the anion with C(14)Iq+ agrees with the Hofmeister series. Such an ion-pair
      formation of anions in W with cations in the RTIL is much weaker when the cation
      constituting the RTIL is a symmetric tetraheptylammonium ion.

PMID- 17552549
TI  - Synthesis of a perpendicular TiO2 nanosheet film with the superhydrophilic
      property without UV irradiation.
AB  - A method was developed for preparing perpendicular TiO2 nanosheet films from
      titanate nanosheet films produced on a titanium metal sheet by hydrothermal
      treatment with aqueous urea. The method is based on the consideration of some
      important points relating to the thermodynamics of nucleation and crystal growth.
      The resulting anatase TiO2 nanosheet films showed a specific superhydrophilicity
      without the need for any prior UV irradiation.

PMID- 17552550
TI  - Proteomic profiling of plasma in Huntington's disease reveals neuroinflammatory
      activation and biomarker candidates.
AB  - Huntington's disease (HD) causes widespread CNS changes and systemic
      abnormalities including endocrine and immune dysfunction. HD biomarkers are
      needed to power clinical trials of potential treatments. We used multiplatform
      proteomic profiling to reveal plasma changes with HD progression. Proteins of
      interest were evaluated using immunoblotting and ELISA in plasma from 2
      populations, CSF and R6/2 mice. The identified proteins demonstrate
      neuroinflammation in HD and warrant further investigation as possible biomarkers.

PMID- 17552551
TI  - Verification of endometrial tissue biomarkers previously discovered using mass
      spectrometry-based proteomics by means of immunohistochemistry in a tissue
      microarray format.
AB  - Verification of candidate protein biomarkers is a necessary step in moving from
      the initial discovery to application. Here, we report results of a verification
      exercise involving six candidate endometrial cancer biomarkers previously
      discovered using mass-tagging and multidimensional liquid chromatography/tandem
      mass spectrometry (DeSouza L., et al. J. Proteome Res. 2005, 4, 377-386) on a
      cohort of 148 patient samples by means of immunohistochemistry on a tissue
      microarray format. A panel of the three best-performing biomarkers, chaperonin
      10, pyruvate kinase M2, and alpha-1-antitrypsin, achieved a sensitivity of 0.85,
      specificity of 0.93, predictive value of 0.90, and positive predictive value of
      0.88 in discriminating malignant from benign endometrium. The ruggedness of this
      panel of biomarkers was verified in a 2/3-training-set-1/3-test-set cross
      validation analysis by randomly splitting the cohort in 10 ways. The roles of
      chaperonin 10 and pyruvate kinase M2 in tumorigenesis confirm them as credible
      cancer biomarkers.

PMID- 17552552
TI  - A force field for molecular simulation of tetrabutylphosphonium amino acid ionic
      liquids.
AB  - An all-atom force field was set up for a new class of ionic liquids (ILs),
      tetrabutylphosphonium amino acid, on the basis of the AMBER force field with
      determining parameters related to the phosphorus atom and modifying several
      parameters. Ab initio quantum chemical calculations were employed to obtain
      molecular geometries, infrared frequencies, and torsion energy profiles. Atom
      partial charges were obtained by using the one-conformation, two-step restraint
      electrostatic potential approach. Molecular dynamics simulation was carried out
      in the isothermal-isobaric ensemble for 14 tetrabutylphosphonium amino acid ILs
      at two temperatures to validate the force field against the experimental
      densities and heat capacities at constant pressure. Computed thermodynamic
      properties are in good agreement with available experimental values. Moreover,
      radial distribution functions were investigated to depict the microscopic
      structures of these ILs.

PMID- 17552553
TI  - Nanostructure changes with Krafft transitions of polyelectrolyte-surfactant
      complexes in aqueous NaCl solutions.
AB  - Nanostructure changes with the Krafft transition of complexes of
      poly(acrylicacid) with octadecyltrimethylammonium (PAA-OTA) in the aqueous
      solutions at various NaCl concentrations (Cs) from 20 to 400 mM, were studied
      making temperature-scanning small-angle X-ray scattering (SAXS) experiments and
      differential scanning calorimetric (DSC) measurements. For the PAA-OTA complex in
      the solution at a higher temperature than 25 degrees C, four SAXS peaks with a
      spacing ratio of 1:31/2:41/2:71/2, indicating the 2D hexagonal structure, were
      observed at Cs below 100 mM and two SAXS peaks with a spacing ratio of 1:2,
      indicating the lamella structure, were observed at Cs above 200 mM. For the
      complex in the solution at a lower temperature than 22 degrees C, a broad SAXS
      peak was observed at the scattering vector q = 1.2 nm-1 when the Cs was less than
      200 mM but not when Cs was 400 mM. Two peaks with a spacing ratio 1:2, indicating
      the lamella structure, were also observed for the complex in the solution at 8
      degrees C. The DSC data demonstrated that the nanostructure changes were
      accompanied with the endothermic enthalpy change. On the basis of the
      experimental results, the salt concentration dependent nanostructures are
      discussed.

PMID- 17552554
TI  - Cationic starches as substitute for synthetic cationic flocculants in solid
      liquid separation of harbor sludge.
AB  - Harbor sludge (about 25% total solid) has to be dredged to keep the waterways
      free. Thus, annually 1.2 million m3 of dredged material has to be cleaned. For
      this process, three different synthetic flocculants with optimal molar masses,
      ionogenities, and concentrations are added in order to get a good dewatering
      efficiency and shear strength of the flocs. But as synthetic flocculants bring
      about unwanted fish toxicity and insufficient biodegradability, this study
      intends to check whether these flocculants can successively be substituted by
      cationic starches which have already been proven to be less toxic than synthetic
      flocculants. Five different starch derivatives with an average degree of
      substitution higher than 0.5 were characterized, especially in terms of the molar
      mass and coil size distribution, and flocculation tests, zeta potential
      measurements and filtrate turbidity tests were carried out in order to create
      optimum flocculation conditions. The flocculation and dewatering measurements
      clearly show that the synthetic cationic flocculant PA (0.2 kg/tTS) can be best
      substituted by cationic starch KS 2 (c = 0.1 kg/tTS, Mw = 1.1 e+08). For
      substitution of PTAC (c = 0.3 kg/tTS) by cationic starches, we observed that a
      maximal dewatering efficiency is reached with an approximately 3-fold dose of KS
      1 (1 kg/tTS, Mw = 8.1 e+07).

PMID- 17552555
TI  - Imaging pancreatic cancer using surface-functionalized quantum dots.
AB  - In this study, CdSe/CdS/ZnS quantum dots (QDs) were used as optical contrast
      agent for imaging pancreatic cancer cells in vitro using transferrin and anti
      Claudin-4 as targeting ligands. CdSe/CdS/ZnS was chosen because the CdSe/CdS/ZnS
      QDs have better photoluminescence (PL) efficiency and stability than those of
      CdSe/ZnS. The transferrin-mediated targeting is demonstrated in both a cell-free
      coprecipitation assay as well as using in vitro confocal microscopy. Pancreatic
      cancer specific uptake is also demonstrated using the monoclonal antibody anti
      Claudin-4. This targeted QD platform will be further modified for the purpose of
      developing as an early detection imaging tool for pancreatic cancer.

PMID- 17552556
TI  - Study of Winsor I to Winsor II transitions in a lattice model.
AB  - Experiments show that with increasing temperature, microemulsion systems undergo
      Winsor transitions. The transitions occur from Winsor I (oil droplets in water
      media) to Winsor II (water droplets in oil media) via Winsor III (bicontinuous
      phase) with an increase in the temperature. In this paper, it has been shown, for
      the first time, how one can study the qualitative effects of temperature, head,
      tail, and oil chain lengths, on these transitions. Simple cubic lattice with
      excluded volume and periodic boundary conditions is used to mimic the box of the
      simulation as a bulk of solution. The simulations have been done using the
      standard traditional Metropolis algorithm in the canonical ensemble (N, V, T).
      Configurational bias Monte Carlo and reptation moves are used with an equal
      probability to relax the systems. A very simple interaction model, i.e., the
      repulsions of water (or heads of surfactants) with oil (or tails of surfactants),
      is used due to the main characteristic of oil-water mixtures or amphiphilic
      molecule that is the hydrophobicity. The interfacial tension between oil and
      water (gammaow) is related to the averaged total energy of the lattice. The model
      shows that the Winsor III has a minimum interfacial tension (gammaow) similar to
      experimental results. Changing the phase structure from Winsor III to Winsor I
      (or Winsor II), increases the interfacial tension which is in agreement with
      experiments. To relate interfacial tension with the interaction parameter, the
      simple theory of Bragg-Williams has been used. All of the results such as the
      effects of oil chain length, head and tail beads number are all similar to the
      experimental results. Using the Davies method for calculating hydrophilic
      lypophilic Balance (HLB), similar to the experimental results, Winsor III phase
      is formed at HLB value nearly to 10.

PMID- 17552557
TI  - Explanation for the apparent absence of collapse of polyelectrolyte brushes in
      the presence of bulky ions.
AB  - The conformational behavior of poly[2-(methacryloyloxy)ethyltrimethylammonium
      chloride] (PMETAC) brushes with different chain density in the presence of large
      benzyltributylammonium chloride (BTBAC) ions has been studied by a Quartz Crystal
      Microbalance with Dissipation (QCM-D) and Scanning Force Microscopy. Dense
      brushes do not collapse in the presence of BTBAC solutions of increasing ionic
      strength, contrary to what is observed in the presence of NaCl. Brush collapse
      can be observed for low-ionic-strength solutions of BTBAC when the brush density
      has been reduced. These phenomena can be explained by considering the Hofmeister
      series as well as ion size and free space in the brush.

PMID- 17552558
TI  - Observation of hierarchical chiral structures in 8-nitrospiropyran monolayers.
AB  - The adsorption and self-organization of racemic mixture of 8-nitrospiropyran
      (SP8) molecules on Au(111) surfaces was studied by scanning tunneling microscopy
      (STM) in ultrahigh vacuum (UHV). The SP8 enantiomers, in spite of their low
      symmetric and nonplanar molecular structures, formed well-ordered monolayers on
      Au(111). In the monolayers, we found two types of enantiomorphous, i.e., mirror
      imaged, 2D chiral domains, denoted as lambda and delta phases. Both phases
      consist of periodically packed chiral quatrefoils. In the lambda domain, the
      quatrefoils are counterclockwise folded, while in the delta domain, the
      quatrefoils are clockwise folded. High-resolution STM images revealed that each
      chiral quatrefoil contains four heterochiral dimers and that each dimer is
      composed of two antiparallelly packed homochiral SP8 molecules. Therefore both of
      the two mirror-imaged 2D chiral structures are not chirally pure but racemic 2D
      crystals. A domain boundary, which serves as the glide reflection line between a
      lambda domain and a delta domain, was also observed along the [11] direction of
      the Au(111) substrate.

PMID- 17552559
TI  - Salt-induced vesicle to micelle transition in aqueous solution of sodium N-(4-n
      octyloxybenzoyl)-L-valinate.
AB  - The self-organization of a single-tailed amino acid based chiral surfactant
      sodium N-(4-n-octyloxybenzoyl)-L-valinate (SOBV) has been studied in water. A
      number of techniques like surface tension, fluorescence probe, dynamic light
      scattering (DLS), transmission electron microscopy (TEM), and atomic force
      microscopy (AFM) have been utilized for characterization of the self-assemblies.
      The amphiphile forms large spherical vesicles of 400-600 nm diameters in dilute
      aqueous solution. However, the vesicles get transformed into spherical micelles
      with increase of surfactant concentration or upon addition of relatively low
      amount (20 mM) of NaCl or KCl. This is the first example of salt-induced vesicle
      to micelle transition (VMT) in a single surfactant system. The vesicles are
      stable in the temperature range of 30-70 degrees C. Cleavage of intermolecular
      hydrogen bonds among the amide groups in the presence of salt appears to be the
      plausible cause for the VMT.

PMID- 17552560
TI  - The effect of aqueous solvation upon alpha-helix formation for polyalanines.
AB  - The incremental free energies of aqueous solution for acetyl(ala)NNH2 in its
      extended unfolded and alpha-helical conformations are compared using the SM5.2
      solvation method of Cramer and Truhlar. A combination of density functional
      theory (DFT) at the B3LYP/D95(d,p) and AM1 has been employed using the ONIOM
      method. The incremental solvation energies of alpha-helical structures are very
      similar for both ONIOM and AM1 optimized structures as these structures do not
      significantly change upon solution. However, the conformations of the unfolded
      peptides change from extended beta-strand to polyproline II conformations upon
      aqueous solution. The incremental solvation free energy per residue of the
      polyproline II structure is about 2 kcal/mol/residue greater than that for the
      alpha-helix, representing an upper limit for the difference between the solvation
      energies. However, most of this difference disappears when the energy required to
      distort the optimized gas-phase extended beta-strand structure to the optimized
      polyproline II solution structure is included in the analysis, leaving an
      estimated difference in incremental solvation free energy of 0.3-0.5 kcal/mol
      favoring the unfolded structure. The solution structure sacrifices the stability
      derived from the intramolecular C5 H-bonds for more favorable interactions with
      the aqueous solvent.

PMID- 17552561
TI  - Self-organization of water in lithium/nitrobenzene system.
AB  - The effect of lithium ion on the ordering of water in water-saturated
      nitrobenzene has been probed by 2H NMR, diffusion ordered spectroscopy and
      neutron scattering. It was shown that increased water concentration in LiClO4/wet
      nitrobenzene results in the formation of a metastable solvatomer with mixed water
      and nitrobenzene character, Li+(W/NB). This species is shown to decay over hours
      to two solvatomers, one dominated by nitrobenzene Li+(NB) and the other dominated
      by water Li+(W). To confirm the assignment of these solvation states, diffusion
      ordered deuterium NMR spectroscopy has been used to elucidate the hydrodynamic
      radii of these solvatomers. Neutron scattering yields vibrational spectroscopy
      information that shows how addition of lithium to the nitrobenzene/water system
      results in relatively slow self-organization of the water environment (hours).

PMID- 17552562
TI  - Preparation of ordered films containing a phenylene ethynylene oligomer by the
      Langmuir-Blodgett technique.
AB  - This paper reports the fabrication and characterization of Langmuir and Langmuir
      Blodgett (LB) films incorporating an oligo(phenylene-ethynylene) (OPE)
      derivative, namely, 4-[4-(4-hexyloxyphenylethynyl)-phenylethynyl]-benzoic acid
      (HBPEB). Conditions appropriate for deposition of monolayers of HBPEB at the air
      water interface have been established and the resulting Langmuir films
      characterized by a combination of surface pressure and surface potential versus
      area per molecule isotherms, Brewster angle microscopy, and ultraviolet
      reflection spectroscopy. The Langmuir films are readily transferred onto solid
      substrates, and one-layer LB films transferred at several surface pressures onto
      mica substrates have been analyzed by means of atomic force microscopy, from
      which it can be concluded that 14 mN/m is an optimum surface pressure of
      transference, giving well-ordered homogeneous films without three-dimensional
      defects and a low surface roughness. The optical and emissive properties of the
      LB films have been determined with significant blue-shifted absorption spectra
      indicating formation of two-dimensional H aggregates and a Stokes shift
      illustrating the effects of the solid-like environment on the molecular
      chromophore.

PMID- 17552563
TI  - Alvaradoins E-N, antitumor and cytotoxic anthracenone C-glycosides from the
      leaves of Alvaradoa haitiensis.
AB  - Bioactivity-directed fractionation of an extract of the leaves of Alvaradoa
      haitiensis, using the KB (human oral epidermoid carcinoma) cell line, led to the
      isolation and identification of 10 new anthracenone C-glycosides, alvaradoins E-N
      (1-10), along with the known compound chrysophanol (11). The cytotoxicity of all
      compounds was evaluated, and preliminary structure-activity relationships are
      suggested. The most potent compounds in the in vitro assays (1 and 2) were
      evaluated in vivo versus the P388 (murine lymphocytic leukemia) model, and
      alvaradoin E (1) showed antileukemic activity (125% T/C) at a dose of 0.2 mg kg-1
      per injection when administered intraperitoneally.

PMID- 17552564
TI  - Organocatalytic sequential one-pot double cascade asymmetric synthesis of Wieland
      Miescher ketone analogues from a Knoevenagel/hydrogenation/Robinson annulation
      sequence: scope and applications of organocatalytic biomimetic reductions.
AB  - A practical and novel organocatalytic chemo- and enantioselective process for the
      cascade synthesis of highly substituted 2-alkyl-cyclohexane-1,3-diones and
      Wieland-Miescher (W-M) ketone analogs is presented via reductive alkylation as a
      key step. First time, we developed the one-step alkylation of dimedone and 1,3
      cyclohexanedione with aldehydes and Hantzsch ester through an organocatalytic
      reductive alkylation strategy. Direct combination of l-proline-catalyzed cascade
      Knoevenagel/hydrogenation and cascade Robinson annulation of CH acids (dimedone
      and 1,3-cyclohexanedione), aldehydes, Hantzsch ester, and methyl vinyl ketone
      furnished the highly functionalized W-M ketone analogues in good to high yields
      and with excellent enantioselectivities. Many of the reductive alkylation
      products show a direct application in pharmaceutical chemistry.

PMID- 17552565
TI  - Synthesis of ladder-type pi-conjugated heteroacenes via palladium-catalyzed
      double N-arylation and intramolecular O-arylation.
AB  - Ladder-type heteroacenes containing pyrrole or furan rings, indolo[3,2
      b]carbazoles and dibenzo[d,d']benzo[1,2-b:4,5-b']difurans, were effectively
      synthesized from the common intermediates, 2,5-bis(o-chloroaryl)hydroquinones.
      The key reactions are palladium-catalyzed double N-arylation of aniline and
      intramolecular O-arylation, which enable regioselective ring closure. In addition
      to the parent indolo[3,2-b]carbazole and dibenzo[d,d']benzo[1,2-b:4,5-b']difuran,
      their derivatives with an alkyl or cyano group were first synthesized.
      Photophysical and electrochemical studies showed that the obtained heteroacenes
      have lower HOMO energy levels and larger band gaps than the corresponding
      hydrocarbon acene, pentacene. An X-ray analysis of dibenzo[d,d']benzo[1,2-b:4,5
      b']difuran revealed that it was packed in herringbone fashion.

PMID- 17552566
TI  - Concurrent cyclopropanation by carbenes and carbanions? A density functional
      theory study on the reaction pathways.
AB  - The mechanisms for the addition reactions of phenylhalocarbenes and
      phenyldihalomethide carbanions with acrylonitrile (ACN) and trimethylethylene
      (TME) have been investigated using an ab initio BH and HLYP/6-31G (d, p) level of
      theory. Solvent effects on these reactions have been explored by calculations
      that included a polarizable continuum model (PCM) for the solvent (THF). These
      model calculations show that for the addition of phenylhalocarbenes, a TME
      species may readily undergo addition reactions with carbenes while ACN has a high
      energy barrier to overcome. It was also found that phenyldihalomethide carbanions
      do not readily add to the electron-rich TME. The cyclopropane yields only appear
      to occur via addition of PhCBr to TME. However, the cyclopropanation proceeds not
      only via slow addition of phenylhalocarbenes to ACN but also forms through the
      stepwise reaction of phenyldihalomethide carbanions with ACN. Our calculation
      results are in good agreement with experimental observations (Moss, R.A.; Tian,
      J.-Z. J. Am. Chem. Soc. 2005, 127, 8960) that indicate that the cyclopropanation
      of phenylhalocarbenes and phenyldihalomethide carbanions with ACN are concurrent
      in THF.

PMID- 17552567
TI  - Palladium(II)-catalyzed isomerization of olefins with tributyltin hydride.
AB  - A new efficient method for the synthesis of geometrically pure (E)-alkenes from
      (Z)-alkenes is described. The reaction of aryl- or alkyl-substituted (Z)-alkenes
      with tributyltin hydride and triethylamine in the presence of a catalytic amount
      of palladium acetate afforded the corresponding (E)-alkenes in good yields.

PMID- 17552568
TI  - Unexpected reactivity of the 9-aminoacridine chromophore in guanidylation
      reactions.
AB  - The 9-aminoacridine chromophore is an important building block of DNA-targeted
      chemotherapeutic agents. The success of 1-[2-(acridin-9-ylamino)ethyl]-1,3
      dimethylthiourea as a carrier group in cytotoxic platinum-intercalator conjugates
      prompted us to explore the synthesis of an analogous guanidine-functionalized
      acridine. In a successful effort to generate such a derivative, various methods
      of guanidylation were employed, which demonstrate that the acridine C9-N9 linkage
      is highly susceptible to electrophilic and nucleophilic attack. The newly
      established reactivities provide efficient pathways to novel cyclic and
      spirocyclic acridine derivatives.

PMID- 17552569
TI  - Synthesis and reactivity of 4-(2-chloro-5-nitrophenyl)-1,2,3-thiadiazole. A novel
      one-pot synthesis of N-substituted indole-2-thiols.
AB  - 4-(2-Chloro-5-nitrophenyl)-1,2,3-thiadiazole undergoes ring opening to produce a
      thioketene intermediate that reacts with an O- or N-nucleophile, forming an ester
      or an amide of the aryl-substituted thioacetic acid. Intermolecular cyclization
      of the thioacetic acid derivative via nucleophilic substitution of halogen in the
      aromatic ring gives an N-substituted indole-2-thiol (in case of an N-nucleophile)
      or a 2-alkoxy-substituted benzo[b]thiophene (in case of an O-nucleophile). The
      reaction is also applicable to the synthesis of heterocyclic analogues of N
      substituted indole-2-thiols: 1-butyl-1,3-dihydropyrrolo[2,3-b]pyridine-2-thione
      was synthesized as an example. In the presence of potassium thioacetate (an S
      nucleophile) 4-nitro-2-(1,2,3-thiadiazol-4-yl)benzenethiol is formed more quickly
      than thiadiazole ring opening occurs, making the heterocyclic ring tolerant
      toward the base.

PMID- 17552571
TI  - Gate electrostatics and quantum capacitance of graphene nanoribbons.
AB  - Capacitance-voltage (C-V) characteristics are important for understanding
      fundamental electronic structures and device applications of nanomaterials. The C
      V characteristics of graphene nanoribbons (GNRs) are examined using self
      consistent atomistic simulations. The results indicate strong dependence of the
      GNR C-V characteristics on the edge shape. For zigzag edge GNRs, highly
      nonuniform charge distribution in the transverse direction due to edge states
      lowers the gate capacitance considerably, and the self-consistent electrostatic
      potential significantly alters the band structure and carrier velocity. For an
      armchair edge GNR, the quantum capacitance is a factor of 2 smaller than its
      corresponding zigzag carbon nanotube, and a multiple gate geometry is less
      beneficial for transistor applications. Magnetic field results in pronounced
      oscillations on C-V characteristics.

PMID- 17552572
TI  - A genetic algorithm approach to probing the evolution of self-organized
      nanostructured systems.
AB  - We present a new methodology, based on a combination of genetic algorithms and
      image morphometry, for matching the outcome of a Monte Carlo simulation to
      experimental observations of a far-from-equilibrium nanosystem. The Monte Carlo
      model used simulates a colloidal solution of nanoparticles drying on a solid
      substrate and has previously been shown to produce patterns very similar to those
      observed experimentally. Our approach enables the broad parameter space
      associated with simulated nanoparticle self-organization to be searched
      effectively for a given experimental target morphology.

PMID- 17552573
TI  - Talker intelligibility differences in cochlear implant listeners.
AB  - People vary in the intelligibility of their speech. This study investigated
      whether across-talker intelligibility differences observed in normally-hearing
      listeners are also found in cochlear implant (CI) users. Speech perception for
      male, female, and child pairs of talkers differing in intelligibility was
      assessed with actual and simulated CI processing and in normal hearing. While
      overall speech recognition was, as expected, poorer for CI users, differences in
      intelligibility across talkers were consistent across all listener groups. This
      suggests that the primary determinants of intelligibility differences are
      preserved in the CI-processed signal, though no single critical acoustic property
      could be identified.

PMID- 17552574
TI  - Classifying multi-frequency fisheries acoustic data using a robust probabilistic
      classification technique.
AB  - A robust probabilistic classification technique, using expectation maximization
      of finite mixture models, is used to analyze multi-frequency fisheries acoustic
      data. The number of clusters is chosen using the Bayesian Information Criterion.
      Probabilities of membership to clusters are used to classify each sample. The
      utility of the technique is demonstrated using two examples: the Gulf of Alaska
      representing a low-diversity, well-known system; and the Mid-Atlantic Ridge, a
      species-rich, relatively unknown system.

PMID- 17552575
TI  - Simulating listener errors in using genetic algorithms for perceptual
      optimization.
AB  - The genetic algorithm (GA) was previously suggested for fitting hearing aid or
      cochlear implant features by using listener's subjective judgment. In the present
      study, two human factors that might affect the outcome of the GA when used for
      perceptual optimization were explored with simulations. Listeners with varying
      sensitivity in discriminating sentences of different intelligibility and with
      varying error rates in entering their judgment to the GA were simulated. A
      comparison of the simulation results with the results from human subjects
      reported by Baskent et al. Ear Hear. 28(3) 277-289 (2007) showed that these
      factors could reduce the performance of the GA considerably.

PMID- 17552576
TI  - Resonant frequency shifts induced by a large spherical object in an air-filled
      acoustic cavity.
AB  - Acoustic resonances are modified when objects are introduced into a chamber. The
      magnitude of these changes depends on the object position, size, and shape, as
      well as on its acoustic properties. Here, an experimental study concerning the
      resonant frequency shifts induced by a solid spherical object in a quasi-one
      dimensional air-filled acoustic cavity is reported. It is shown that Leung's
      theory does not account quantitatively for the observations. A novel and simple
      approach is proposed, based on the wave equation in a cavity of variable cross
      section. The results fit more accurately the measured frequency shifts.

PMID- 17552577
TI  - Hybrid passive-active absorption of a microperforated panel in free field
      conditions.
AB  - Although hybrid passive-active absorption in impedance tubes has been widely
      analyzed, its study in more realistic conditions remains to be accomplished. This
      letter describes the practical measurement of the passive-active absorption
      coefficient in a free field. The passive absorber consists of a microperforated
      panel backed by an air cavity and a wooden panel. A multichannel active system
      controls the sound pressure in a reduced cell behind the absorber. Measured
      absorption coefficients between 200 and 400 Hz account for 0.2-0.4 and 0.72-0.75,
      in the passive and active cases, respectively, and above 500 Hz both are
      comparable.

PMID- 17552578
TI  - Directive sources in acoustic discrete-time domain simulations based on
      directivity diagrams.
AB  - Discrete-time domain methods provide a simple and flexible way to solve initial
      boundary value problems. With regard to the sources in such methods, only
      monopoles or dipoles can be considered. However, in many problems such as room
      acoustics, the radiation of realistic sources is directional-dependent and their
      directivity patterns have a clear influence on the total sound field. In this
      letter, a method to synthesize the directivity of sources is proposed, especially
      in cases where the knowledge is only based on discrete values of the directivity
      diagram. Some examples have been carried out in order to show the behavior and
      accuracy of the proposed method.

PMID- 17552579
TI  - Phase velocity and normalized broadband ultrasonic attenuation in Polyacetal
      cuboid bone-mimicking phantoms.
AB  - The variations of phase velocity and normalized broadband ultrasonic attenuation
      (nBUA) with porosity were investigated in Polyacetal cuboid bone-mimicking
      phantoms with circular cylindrical pores running normal to the surface along the
      three orthogonal axes. The frequency-dependent phase velocity and attenuation
      coefficient in the phantoms with porosities from 0% to 65.9% were measured from
      0.65 to 1.10 MHz. The results showed that the phase velocity at 880 kHz decreased
      linearly with porosity, whereas the nBUA increased linearly with porosity. This
      study provides a useful insight into the relationships between ultrasonic
      properties and porosity in bone at porosities lower than 70%.

PMID- 17552582
TI  - 2007 Medwin Prize in acoustical oceanography awarded to Brian Dushaw.

PMID- 17552678
TI  - Retrofocusing techniques in a waveguide for acoustic communications.
AB  - In the paper "Retrofocusing technique for high rate acoustic communications" [M.
      Stojanovic, J. Acoust. Soc. Am. 117, 1173-1185 (2005)], it is suggested that the
      time reversal approach requires a large number of array elements to compete with
      other approaches. Here the analysis of that paper is extended with a modified
      example to compare the performance of various approaches in three respects: (1)
      array element distribution across the water column, (2) channel normalization,
      and (3) phase delay across the array. In contrast, our results show that the time
      reversal approach combined with channel equalization can offer nearly optimal
      performance with a very small four element array.

PMID- 17552679
TI  - On the relation between the phonation threshold lung pressure and the oscillation
      frequency of the vocal folds.
AB  - This Letter presents an extension of a previous equation for the phonation
      threshold pressure by Titze [I. R. Titze, J. Acoust. Soc. Am. 83, 1536-1552
      (1988)]. The extended equation contains the vocal-fold oscillation frequency as
      an explicit factor. It is derived from the mucosal wave model of the vocal folds
      by considering the general case of an arbitrary time delay for the mucosal wave
      to travel the glottal height. The results are illustrated with a numerical
      example, which shows good qualitative agreement with experimental measures.

PMID- 17552680
TI  - A modified diffusion equation for room-acoustic predication.
AB  - This letter presents a modified diffusion model using an Eyring absorption
      coefficient to predict the reverberation time and sound pressure distributions in
      enclosures. While the original diffusion model [Ollendorff, Acustica 21, 236-245
      (1969); J. Picaut et al., Acustica 83, 614-621 (1997); Valeau et al., J. Acoust.
      Soc. Am. 119, 1504-1513 (2006)] usually has good performance for low absorption,
      the modified diffusion model yields more satisfactory results for both low and
      high absorption. Comparisons among the modified model, the original model, a
      geometrical-acoustics model, and several well-established theories in terms of
      reverberation times and sound pressure level distributions, indicate
      significantly improved prediction accuracy by the modification.

PMID- 17552681
TI  - Complete transmission through a periodically perforated rigid slab.
AB  - The propagation of a normally incident plane acoustic wave through a three
      dimensional rigid slab with periodically placed holes is modeled and analyzed.
      The spacing of the holes A and B, the wavelength lambda, and the thickness of the
      slab L are order one parameters compared to the characteristic size D of the
      holes, which is a small quantity. Scattering matrix techniques are used to derive
      expressions for the transmission and reflection coefficients of the lowest mode.
      These expressions depend only on the transmission coefficient, tau(0), of an
      infinitely long slab with the same configuration. The determination of tau(0)
      requires the solution of an infinite set of algebraic equations. These equations
      are approximately solved by exploiting the small parameter D/square root(AB).
      Remarkably, this structure is transparent at certain frequencies and opaque for
      all others. Such a structure may be useful in constructing narrow-band filters
      and resonators.

PMID- 17552682
TI  - Acoustic scattering by a rigid elliptic cylinder in a slightly viscous medium.
AB  - A complete solution is obtained for the two-dimensional diffraction of a time
      harmonic acoustic plane wave by an impenetrable elliptic cylinder in a viscous
      fluid. Arbitrary size, ellipticity, and angle of incidence are considered. The
      linearized equations of viscous flow are used to write down expressions for the
      dilatation and vorticity in terms of products of radially and angular dependent
      Mathieu functions. The no-slip condition on the rigid boundary then determines
      the coefficients. The resulting computations are facilitated by recently
      developed library routines for complex input parameters. The solution for the
      circular cylinder serves as a guide and a differently constructed solution for
      the strip is also given. Typical results in the "resonant" range of dimensionless
      wave number, displaying the surface vorticity and the far-field scattering
      pattern are included, with the latter allowing comparison with the inviscid case.

PMID- 17552683
TI  - Fresnel approximations for acoustic fields of rectangularly symmetric sources.
AB  - A general approach is presented for determining the acoustic fields of
      rectangularly symmetric, baffled, time-harmonic sources under the Fresnel
      approximation. This approach is applicable to a variety of separable source
      configurations, including uniform, exponential, Gaussian, sinusoidal, and error
      function surface velocity distributions, with and without focusing in either
      surface dimension. In each case, the radiated field is given by a formula similar
      to that for a uniform rectangular source, except for additional scaling of wave
      number and azimuthal distance parameters. The expressions presented are
      generalized to three different Fresnel approximations that correspond,
      respectively, to diffracted plane waves, diffracted spherical waves, or
      diffracted cylindrical waves. Numerical results, for several source geometries
      relevant to ultrasonic applications, show that these expressions accurately
      depict the radiated pressure fields, except for points very near the radiating
      aperture. Highest accuracy near the source is obtained by choice of the Fresnel
      approximation most suited to the source geometry, while the highest accuracy far
      from the source is obtained by the approximation corresponding to diffracted
      spherical waves. The methods are suitable for volumetric computations of acoustic
      fields including focusing, apodization, and attenuation effects.

PMID- 17552684
TI  - Liquid jet response to internal modulated ultrasonic radiation pressure and
      stimulated drop production.
AB  - Experimental evidence shows that a liquid jet in air is an acoustic waveguide
      having a cutoff frequency inversely proportional to the jet diameter. Ultrasound
      applied to the jet supply liquid can propagate within the jet when the acoustic
      frequency is near to or above the cutoff frequency. Modulated radiation pressure
      is used to stimulate large amplitude deformations and the breakup of the jet into
      drops. The jet response to the modulated internal ultrasonic radiation pressure
      was monitored along the jet using (a) an optical extinction method and (b) images
      captured by a video camera. The jet profile oscillates at the frequency of the
      radiation pressure modulation and where the response is small, the amplitude was
      found to increase in proportion to the square of the acoustic pressure amplitude
      as previously demonstrated for oscillating drops [P.L. Marston and R.E. Apfel, J.
      Acoust. Soc. Am. 67, 27-37 (1980)]. Small amplitude deformations initially grow
      approximately exponentially with axial distance along the jet. Though aspects of
      the perturbation growth can be approximated from Rayleigh's analysis of the
      capillary instability, some detailed features of the observed jet response to
      modulated ultrasound are unexplained neglecting the effects of gravity.

PMID- 17552685
TI  - Maxwell rheological model for lipid-shelled ultrasound microbubble contrast
      agents.
AB  - The present paper proposes a model that describes the encapsulation of
      microbubble contrast agents by the linear Maxwell constitutive equation. The
      model also incorporates the translational motion of contrast agent microbubbles
      and takes into account radiation losses due to the compressibility of the
      surrounding liquid. To establish physical features of the proposed model,
      comparative analysis is performed between this model and two existing models, one
      of which treats the encapsulation as a viscoelastic solid following the Kelvin
      Voigt constitutive equation and the other assumes that the encapsulating layer
      behaves as a viscous Newtonian fluid. Resonance frequencies, damping
      coefficients, and scattering cross sections for the three shell models are
      compared in the regime of linear oscillation. Translational displacements
      predicted by the three shell models are examined by numerically calculating the
      general, nonlinearized equations of motion for weakly nonlinear excitation.
      Analogous results for free bubbles are also presented as a basis to which
      calculations made for encapsulated bubbles can be related. It is shown that the
      Maxwell shell model possesses specific physical features that are unavailable in
      the two other models.

PMID- 17552686
TI  - Optical measurements of the self-demodulated displacement and its interpretation
      in terms of radiation pressure.
AB  - Using a sensitive optical interferometer, the low frequency displacement
      nonlinearly generated by an ultrasonic tone burst propagating in a liquid is
      studied. Close to the source, the low frequency displacement contains a quasi
      static component, which is affected by diffraction effects farther from the
      transducer. The experimental setup provides quantitative results, which allow the
      determination of the nonlinearity parameter of the liquid with a good accuracy.
      Such measurements are carried out in water and ethanol. Finally, the pressure
      associated with the low frequency displacement is discussed. Introducing the
      temporal mean value of the displacement, as already done in lossless solids, the
      noncumulative part of this second order pressure is associated with the static
      part of the low frequency displacement. This interpretation leads to extend the
      definition of the Rayleigh radiation pressure usually introduced for a continuous
      plane wave radiated in a confined fluid.

PMID- 17552687
TI  - Causality and the velocity of acoustic signals in bubbly liquids.
AB  - Several versions of the dispersion formula governing the acoustic propagation in
      bubbly liquids are shown to exhibit acausal behavior. The cause of this behavior
      is due to the inappropriate application of a low frequency approximation in the
      determination of the extinction of the signal from radiative scattering. Using a
      corrected causal formula, several principles of wave propagation in bubbly media
      consistent with the general theory of wave propagation in dispersive media are
      demonstrated: There exist two precursors to any finite signal. Both propagate
      without regard to the source characteristics at velocities, frequencies, and
      amplitudes dependent wholly upon the characteristics of the medium supporting the
      wave motion. The first travels at the infinite frequency phase velocity that is
      coincident with the infinite frequency limit of the group velocity. That part of
      a propagating wave oscillating at the source frequency arrives at a time
      determined by the signal velocity. Analogous to the well known signal velocity of
      electromagnetic wave propagation in conducting media, the value of the signal
      velocity depends on the detailed structure of the dispersion formula in the
      complex frequency plane.

PMID- 17552688
TI  - Observable parameters from multipath bottom reverberation in shallow water.
AB  - Multipath ocean reverberation originating from the seabed in shallow isovelocity
      water, with particular attention to its information content in the cylindrical
      spreading and mode stripping regions, is considered. The reverberation is
      evaluated using Weston's flux integral method, both analytically with various
      simplifying approximations and numerically with all but one of these
      approximations rescinded. The functional form of the analytical solution is used
      to infer which physical seabed parameters can be extracted from measurements of
      reverberation. Coarse- and fine-grained sediments (sand and clay) are both
      considered. The main purpose of the numerical solutions is to check the accuracy
      of the analytical approximations; they also serve as a convenient surrogate for
      measured reverberation.

PMID- 17552689
TI  - Ocean acoustic interferometry.
AB  - Ocean acoustic interferometry refers to an approach whereby signals recorded from
      a line of sources are used to infer the Green's function between two receivers.
      An approximation of the time domain Green's function is obtained by summing, over
      all source positions (stacking), the cross-correlations between the receivers.
      Within this paper a stationary phase argument is used to describe the
      relationship between the stacked cross-correlations from a line of vertical
      sources, located in the same vertical plane as two receivers, and the Green's
      function between the receivers. Theory and simulations demonstrate the approach
      and are in agreement with those of a modal based approach presented by others.
      Results indicate that the stacked cross-correlations can be directly related to
      the shaded Green's function, so long as the modal continuum of any sediment
      layers is negligible.

PMID- 17552690
TI  - An extended coupled phase theory for the sound propagation in polydisperse
      concentrated suspensions of rigid particles.
AB  - An extension of the classical coupled phase theory is proposed to account for
      hydrodynamic interactions between neighboring rigid particles, which are
      essential to describe properly the sound propagation in concentrated suspensions.
      Rigorous ensemble-averaged equations are derived for each phase and simplified in
      the case of acoustical wave propagation. Then, closure is achieved by introducing
      a self-consistent scheme originally developed by Buyevich and Shchelchkova [Prog.
      Aerosp. Sci. 18, 121-151 (1978)] for incompressible flows, to model the transfer
      terms between the two phases. This provides an alternative to the effective
      medium self-consistent theory developed by Spelt et al. [J. Fluid Mech. 430, 51
      86 (2001)] in which the suspension is considered as a whole. Here, a
      significantly simpler formulation is obtained in the long wavelength regime.
      Predictions of this self-consistent theory are compared with the classical
      coupled phase theory and with experimental data measuring the attenuation in
      concentrated suspensions of silica in water. Our calculation is shown to give a
      good description of the attenuation variation with volume fraction. This theory
      is also extended to the case of polydisperse suspensions. Finally, the link
      between the self-consistent theory and the different orders of the multiple
      scattering theory is clarified.

PMID- 17552691
TI  - Numerical investigation of elastic modes of propagation in helical waveguides.
AB  - Steel multi-wire cables are widely employed in civil engineering. They are
      usually made of a straight core and one layer of helical wires. In order to
      detect material degradation, nondestructive evaluation methods based on
      ultrasonics are one of the most promising techniques. However, their use is
      complicated by the lack of accurate cable models. As a first step, the goal of
      this paper is to propose a numerical method for the study of elastic guided waves
      inside a single helical wire. A finite element (FE) technique is used based on
      the theory of wave propagation inside periodic structures. This method avoids the
      tedious writing of equilibrium equations in a curvilinear coordinate system
      yielding translational invariance along the helix centerline. Besides, no
      specific programming is needed inside a conventional FE code because it can be
      implemented as a postprocessing step of stiffness, mass and damping matrices. The
      convergence and accuracy of the proposed method are assessed by comparing FE
      results with Pochhammer-Chree solutions for the infinite isotropic cylinder.
      Dispersion curves for a typical helical waveguide are then obtained. In the low
      frequency range, results are validated with a helical Timoshenko beam model. Some
      significant differences with the cylinder are observed.

PMID- 17552692
TI  - Reflection and transmission coefficients for guided waves reflected by defects in
      viscoelastic material plates.
AB  - The paper presents a Fourier transform-based signal processing procedure for
      quantifying the reflection and transmission coefficients and mode conversion of
      guided waves diffracted by defects in plates made of viscoelastic materials. The
      case of the S(0) Lamb wave mode incident on a notch in a Perspex plate is
      considered. The procedure is applied to numerical data produced by a finite
      element code that simulates the propagation of attenuated guided modes and their
      diffraction by the notch, including mode conversion. Its validity and precision
      are checked by the way of the energy balance computation and by comparison with
      results obtained using an orthogonality relation-based processing method.

PMID- 17552693
TI  - Multiple scattering from assemblies of dislocation walls in three dimensions.
      Application to propagation in polycrystals.
AB  - The attenuation of ultrasound in polycrystalline materials is modeled with grain
      boundaries considered as arrays of dislocation segments, a model valid for low
      angle mismatches. The polycrystal is thus studied as a continuous medium
      containing many dislocation "walls" of finite size randomly placed and oriented.
      Wave attenuation is blamed on the scattering by such objects, an effect that is
      studied using a multiple scattering formalism. This scattering also renormalizes
      the speed of sound, an effect that is also calculated. At low frequencies,
      meaning wavelengths that are long compared to grain boundary size, then
      attenuation is found to scale with frequency following a law that is a linear
      combination of quadratic and quartic terms, in agreement with the results of
      recent experiments performed in copper [Zhang et al., J. Acoust. Soc. Am. 116(1),
      109-116 (2004)]. The prefactor of the quartic term can be obtained with
      reasonable values for the material under study, without adjustable parameters.
      The prefactor of the quadratic term can be fit assuming that the drag on the
      dynamics of the dislocations making up the wall is one to two orders of magnitude
      smaller than the value usually accepted for isolated dislocations. The quartic
      contribution is compared with the effect of the changes in the elastic constants
      from grain to grain that is usually considered as the source of attenuation in
      polycrystals. A complete model should include this scattering as well.

PMID- 17552694
TI  - Effect of nuclei concentration on cavitation cluster dynamics.
AB  - Cavitation cluster dynamics after the passage of a single pressure wave is
      studied for different concentrations of artificial cavitation nuclei (30 to
      3x10(5) nuclei/ml). With increasing concentration of cavitation nuclei the
      lifetime of the cavitation cluster is prolonged. Additionally, it is found that
      the spatial extent of the cluster decreases with higher nuclei concentration. The
      experimental data for concentrations less than 400 nuclei/ml are compared to
      simulations with a Rayleigh-Plesset-type equation, taking into account bubble
      bubble interaction. For higher concentrations (more than 1000 nuclei/ml) the
      observed radial cluster dynamics is compared with calculations from an
      axisymmetric cavity-collapse model.

PMID- 17552695
TI  - A Green's function method for surface acoustic waves in functionally graded
      materials.
AB  - Acoustic wave propagation in anisotropic media with one-dimensional inhomogeneity
      is discussed. Using a Green's function approach, the wave equation with
      inhomogeneous variation of elastic property and mass density is transformed into
      an integral equation, which is then solved numerically. The method is applied to
      find the dispersion relation of surface acoustic waves for a medium with
      continuously or discontinuously varying elastic property and mass density
      profiles.

PMID- 17552696
TI  - Simulation of ultrasonic-driven gas separations.
AB  - The separation of components in a gas mixture is important for a wide range of
      applications. One method for achieving this separation is by passing a traveling
      acoustic wave through the gas mixture, which creates a flux of the lighter
      components away from the transducer. A series of simulations was performed to
      assess the effectiveness of this method for separating a binary mixture of argon
      and helium using the lattice kinetics method. The energy transport equation was
      modified to account for adiabatic expansion and compression. The species
      transport equation was modified to include a barodiffusion term. Simulations were
      performed on two different scales; detailed acoustic wave simulations to
      determine the net component flux as a function of local concentration, pressure,
      etc. and device scale simulations to predict the gas composition as a function of
      time inside a gas separation cylinder. The method is first validated using data
      from literature and then applied to mixtures of argon and helium. Results are
      presented and discussed.

PMID- 17552697
TI  - k-space propagation models for acoustically heterogeneous media: application to
      biomedical photoacoustics.
AB  - Biomedical applications of photoacoustics, in particular photoacoustic
      tomography, require efficient models of photoacoustic propagation that can
      incorporate realistic properties of soft tissue, such as acoustic inhomogeneities
      both for purposes of simulation and for use in model-based image reconstruction
      methods. k-space methods are well suited to modeling high-frequency acoustics
      applications as they require fewer mesh points per wavelength than conventional
      finite element and finite difference models, and larger time steps can be taken
      without a loss of stability or accuracy. They are also straightforward to encode
      numerically, making them appealing as a general tool. The rationale behind k
      space methods and the k-space approach to the numerical modeling of photoacoustic
      waves in fluids are covered in this paper. Three existing k-space models are
      applied to photoacoustics and demonstrated with examples: an exact model for
      homogeneous media, a second-order model that can take into account heterogeneous
      media, and a first-order model that can incorporate absorbing boundary
      conditions.

PMID- 17552698
TI  - Broadband multimode baffled piezoelectric cylindrical shell transducers.
AB  - Hollow piezoelectric cylindrical shell transducers may be made directional for
      underwater acoustic applications by the use of suitable acoustical baffles and
      the operational bandwidth may be extended by using multiple resonant modes. A
      theoretical and experimental investigation was performed for circumferentially
      baffled piezoelectric cylindrical shell transducers operating in the zero and one
      modes of extensional vibration. The frequency responses and directivity patterns
      were analyzed under various conditions of energizing separate halves of
      electrodes. It was found that the broadest frequency response with nearly
      constant beamwidth can be obtained when the two halves of the piezoelectric ring
      are electromechanically excited 90 deg out-of-phase. The experimental results
      obtained with a proof-of-concept transducer were in good agreement with the
      theoretical predictions.

PMID- 17552699
TI  - High frequency vibration analysis by the complex envelope vectorization.
AB  - The complex envelope displacement analysis (CEDA) is a procedure to solve high
      frequency vibration and vibro-acoustic problems, providing the envelope of the
      physical solution. CEDA is based on a variable transformation mapping the high
      frequency oscillations into signals of low frequency content and has been
      successfully applied to one-dimensional systems. However, the extension to plates
      and vibro-acoustic fields met serious difficulties so that a general revision of
      the theory was carried out, leading finally to a new method, the complex envelope
      vectorization (CEV). In this paper the CEV method is described, underlying merits
      and limits of the procedure, and a set of applications to vibration and vibro
      acoustic problems of increasing complexity are presented.

PMID- 17552700
TI  - Locating air leaks in manned spacecraft using structure-borne noise.
AB  - All manned spacecraft are vulnerable to leaks generated by micrometeorite or
      debris impacts. Methods for locating such leaks using leak-generated, structure
      borne ultrasonic noise are discussed and demonstrated. Cross-correlations of
      ultrasonic noise waveforms from a leak into vacuum are used to find the location
      of the leak. Four methods for sensing and processing leak noise have been
      developed and tested and each of these can be used to reveal the leak location.
      The methods, based on phased-array, distributed sensor, and dual sensor
      approaches, utilize the propagation patterns of guided ultrasonic Lamb waves in
      the spacecraft skin structure to find the source or direction of the leak noise.
      It is shown that each method can be used to successfully locate the leak to
      within a few millimeters on a 0.6-m2 aluminum plate. The relative merits of the
      four methods are discussed.

PMID- 17552701
TI  - Measurement of structural intensity using boundary element method-based nearfield
      acoustical holography.
AB  - The regularization method for measurement of structural intensity (SI) using
      boundary element method (BEM)-based nearfield acoustical holography (NAH) is
      proposed. Spatial derivatives of normal displacement are necessary to obtain the
      structural intensity. The derivative operations amplify high-wavenumber component
      of measurement noise and contaminate the measurement result of SI. To overcome
      this difficulty, regularization method for measurement of SI using fast Fourier
      transform-based NAH has been introduced. In this paper, this regularization
      method is modified for the BEM-based NAH. The BEM-based NAH avoids the aperture
      replication problem; therefore, measurement aperture for BEM-based NAH can be set
      smaller than that for FFT-based NAH. The effectiveness of the proposed method is
      demonstrated by experiments.

PMID- 17552702
TI  - Quieting Weinberg 5C: a case study in hospital noise control.
AB  - Weinberg 5C of Johns Hopkins Hospital is a very noisy hematological cancer unit
      in a relatively new building of a large medical campus. Because of the
      requirements for dealing with immuno-suppressed patients, options for introducing
      sound absorbing materials are limited. In this article, a case study of noise
      control in a hospital, the sound environment in the unit before treatment is
      described, the chosen noise control approach of adding custom-made sound
      absorbing panels is presented, and the impact of the noise control installation
      is discussed. The treatment of Weinberg 5C involved creating sound absorbing
      panels of 2-in.-thick fiberglass wrapped in an anti-bacterial fabric. Wallpaper
      paste was used to hold the fabric to the backing of the fiberglass. Installation
      of these panels on the ceiling and high on corridor walls had a dramatic effect.
      The noise on the unit (as measured by the equivalent sound pressure level) was
      immediately reduced by 5 dB(A) and the reverberation time dropped by a factor of
      over 2. Further, this drop in background noise and reverberation time understates
      the dramatic impact of the change. Surveys of staff and patients before and after
      the treatment indicated a change from viewing the unit as very noisy to a view of
      the unit as relatively quiet.

PMID- 17552703
TI  - An alternative Biot's displacement formulation for porous materials.
AB  - This paper proposes an alternative displacement formulation of Biot's linear
      model for poroelastic materials. Its advantage is a simplification of the
      formalism without making any additional assumptions. The main difference between
      the method proposed in this paper and the original one is the choice of the
      generalized coordinates. In the present approach, the generalized coordinates are
      chosen in order to simplify the expression of the strain energy, which is
      expressed as the sum of two decoupled terms. Hence, new equations of motion are
      obtained whose elastic forces are decoupled. The simplification of the formalism
      is extended to Biot and Willis thought experiments, and simpler expressions of
      the parameters of the three Biot waves are also provided. A rigorous derivation
      of equivalent and limp models is then proposed. It is finally shown that, for the
      particular case of sound-absorbing materials, additional simplifications of the
      formalism can be obtained.

PMID- 17552704
TI  - Ceiling baffles and reflectors for controlling lecture-room sound for speech
      intelligibility.
AB  - Reinforcing speech levels and controlling noise and reverberation are the
      ultimate acoustical goals of lecture-room design to achieve high speech
      intelligibility. The effects of sound absorption on these factors have opposite
      consequences for speech intelligibility. Here, novel ceiling baffles and
      reflectors were evaluated as a sound-control measure, using computer and 1/8
      scale models of a lecture room with hard surfaces and excessive reverberation.
      Parallel ceiling baffles running front to back were investigated. They were
      expected to absorb reverberation incident on the ceiling from many angles, while
      leaving speech signals, reflecting from the ceiling to the back of the room,
      unaffected. Various baffle spacings and absorptions, central and side speaker
      positions, and receiver positions throughout the room, were considered.
      Reflective baffles controlled reverberation, with a minimum decrease of sound
      levels. Absorptive baffles reduced reverberation, but reduced speech levels
      significantly. Ceiling reflectors, in the form of obstacles of semicircular cross
      section, suspended below the ceiling, were also tested. These were either 7 m
      long and in parallel, front-to-back lines, or 0.8 m long and randomly
      distributed, with flat side up or down, and reflective or absorptive top
      surfaces. The long reflectors with flat side down and no absorption were somewhat
      effective; the other configurations were not.

PMID- 17552705
TI  - On the sound field of a shallow spherical shell in an infinite baffle.
AB  - A method is presented for calculating the far field sound radiation from a
      shallow spherical shell in an acoustic medium. The shell has a concentrated ring
      mass boundary condition at its perimeter representing a loudspeaker voice coil
      and is excited by a concentrated ring force exerted by the end of the voice coil.
      A Green's function is developed for a shallow spherical shell, which is based
      upon Reissner's solution to the shell wave equation [Q. Appl. Math. 13, 279-290
      (1955)]. The shell is then coupled to the surrounding acoustic medium using an
      eigenfunction expansion, with unknown coefficients, for its deflection. The
      resulting surface pressure distribution is solved using the King integral
      together with the free space Green's function in cylindrical coordinates. In
      order to eliminate the need for numerical integration, the radiation (coupling)
      integrals are solved analytically to yield fast converging expansions. Hence, a
      set of simultaneous equations is obtained which is solved for the coefficients of
      the eigenfunction expansion. These coefficients are finally used in formulas for
      the far field sound radiation.

PMID- 17552706
TI  - Properties of an entropy-based signal receiver with an application to ultrasonic
      molecular imaging.
AB  - Qualitative and quantitative properties of the finite part, H(f), of the Shannon
      entropy of a continuous waveform f(t) in the continuum limit are derived in order
      to illuminate its use for waveform characterization. Simple upper and lower
      bounds on H(f), based on features of f(t), are defined. Quantitative criteria for
      a priori estimation of the average-case variation of H(f) and log E(f), where
      E(f) is the signal energy of f(t) are also derived. These provide relative
      sensitivity estimates that could be used to prospectively choose optimal imaging
      strategies in real-time ultrasonic imaging machines, where system bandwidth is
      often pushed to its limits. To demonstrate the utility of these sensitivity
      relations for this application, a study designed to assess the feasibility of
      identification of angiogenic neovasculature targeted with perfluorocarbon
      nanoparticles that specifically bind to alpha(v)beta3-integrin expression in
      tumors was performed. The outcome of this study agrees with the prospective
      sensitivity estimates that were used for the two receivers. Moreover, these data
      demonstrate the ability of entropy-based signal receivers when used in
      conjunction with targeted nanoparticles to elucidate the presence of
      alpha(v)beta3 integrins in primordial neovasculature, particularly in
      acoustically unfavorable environments.

PMID- 17552707
TI  - Statistical modeling of intrinsic structures in impacts sounds.
AB  - This paper presents a statistical data-driven method for learning intrinsic
      structures of impact sounds. The method applies principal and independent
      component analysis to learn low-dimensional representations that model the
      distribution of both the time-varying spectral and amplitude structure. As a
      result, the method is able to decompose sounds into a small number of underlying
      features that characterize acoustic properties such as ringing, resonance,
      sustain, decay, and onsets. The method is highly flexible and makes no a priori
      assumptions about the physics, acoustics, or dynamics of the objects. In
      addition, by modeling the underlying distribution, the method can capture the
      natural variability of ensembles of related impact sounds.

PMID- 17552708
TI  - Directionality of generalized acoustic sensors of arbitrary order.
AB  - For several decades there has been a great deal of interest in acoustic sensors
      that can make multiple measurements at a single point in the ocean. The order of
      such sensors has been defined by linking it to the order of the Taylor series
      approximation of the pressure field at that point. Following this definition, the
      pressure, vector, and dyadic sensor is of order zero, one, and two, respectively.
      For this theoretical study, a multichannel three-dimensional spatial filter is
      derived for a directional acoustic sensor of arbitrary order. Explicit formulas
      are found for the filter coefficients that maximize the array gain (directivity
      index) of the filter as well as an explicit expression for the maximum array gain
      (directivity index). This process is repeated for the case of a first-order null
      placed in the direction opposite to the look direction of the multichannel
      filter. Finally, an example is presented which tracks the array gain and
      beamwidth of a third-order acoustic sensor as the order of the null is assigned
      values 0, 1, 2, and 3.

PMID- 17552709
TI  - The two-dimensional source location problem for time differences of arrival at
      minimal element monitoring arrays.
AB  - The time difference of arrival (TDOA) source localization inverse problem is
      analyzed for two-dimensional signal propagation detected by a small number of
      sensor elements in a monitoring array. Nonlinear least-squares solutions are
      found based on the assumptions of geodesic rays propagating at constant speed.
      The two-dimensional (2D) TDOA source location problem is shown in the case of
      three sensors to have dual possible solutions for some combinations of arrival
      time differences. In the case of four non-collinear sensors, there are unique
      solutions for all physically possible combinations of time differences. Dual
      solutions to the three-sensor problem are associated with a small range of
      arrival time differences but large regions in physical space. The locations of
      the dual solutions are separated by a wide variety of distances, which in some
      cases prevent the use of alternative reasoning to remove the ambiguity. Three
      sensor TDOA cannot be reliably used for 2D source location unless the source is a
      priori known to be within either the spatial region spanned by the sensor array
      or the external zones of unique solution. Determining the minimum number of
      sensors necessary to unambiguously solve the source location problem assists in
      cost-effective design of sensor arrays.

PMID- 17552710
TI  - An exact noniterative linear method for locating sources based on measuring
      receiver arrival times.
AB  - In this paper an exact, linear solution to the source localization problem based
      on the time of arrival at the receivers is presented. The method is unique in
      that the source's position can be obtained by solving a system of linear
      equations, three for a plane and four for a volume. This simplification means
      adding an additional receiver to the minimum mathematically required (3+1 in two
      dimensions and 4+1 in three dimensions). The equations are easily worked out for
      any receiver configuration and their geometrical interpretation is
      straightforward. Unlike other methods, the system of reference used to describe
      the receivers' positions is completely arbitrary. The relationship between this
      method and previously published ones is discussed, showing how the present, more
      general, method overcomes nonlinearity and unknown dependency issues.

PMID- 17552711
TI  - Near-field time-reversal amplification.
AB  - The spatial resolution of the focused field of a classical time-reversal mirror
      has a wavelength-order lambda diffraction limit. Previously reported results for
      subwavelength focus require either the full knowledge of the original source or
      the evanescent waves in the near field. Here it is shown that subwavelength
      focusing can be achieved without a priori knowledge of the original probe source.
      If the field is recorded at a few wavelengths away from the probe source, where
      the amplitude of the near field is too low for subwavelength focusing, it is
      shown that the low amplitude near field can be amplified and the spatial
      resolution improved, using the near-field time reversal (NTR) procedure
      introduced here. The NTR is performed from the phase of the spatial spectrum of
      the field recorded on an array around the original probe source using an
      analytical continuation for the amplitude of the spatial spectrum. Following
      theory, lambda/20 resolution is experimentally demonstrated with audible acoustic
      wavefields in the air.

PMID- 17552712
TI  - Wideband ipsilateral measurements of middle-ear muscle reflex thresholds in
      children and adults.
AB  - The goals of the current study were to: 1) evaluate the feasibility of a new
      wideband approach to measuring middle-ear muscle reflex (MEMR) status, and 2) to
      test the hypothesis that ipsilateral thresholds elicited with 1 or 2 kHz tones
      and broadband noise activators on a wideband acoustic transfer function (WATF)
      system are lower than thresholds elicited on a clinical system. Clinical MEMR
      tests have limitations, including the need for high activator levels to elicit a
      shift in a narrowband probe (e.g., a 0.226 or 1 kHz tone). Wideband MEMR tests
      using WATFs may elicit the reflex at lower levels because a wideband probe
      (click) is used and the threshold detection criterion can be wideband. Mean
      wideband MEMR thresholds across 40 normal-hearing adult ears were 2.2-4.0 dB
      lower than clinical MEMR thresholds, depending on the activator and specific WATF
      test used (admittance magnitude or energy reflectance). Wideband MEMR has
      potential clinical utility beyond the adult population, including use in newborn
      and preschool hearing screenings. In a newborn hearing screening, for example,
      wideband MEMR could be completed with the same system as otoacoustic emissions.
      However, further investigations in infants and young children are needed.

PMID- 17552713
TI  - Distortion product otoacoustic emission suppression tuning and acoustic
      admittance in human infants: birth through 6 months.
AB  - Previous work has reported non-adultlike distortion product otoacoustic emission
      (DPOAE) suppression in human newborns at f2=6000 Hz, indicating an immaturity in
      peripheral auditory function. In this study, DPOAE suppression tuning curves
      (STCs) were recorded as a measure of cochlear function and acoustic
      admittance/reflectance (YR) in the ear canal recorded as a measure of middle-ear
      function, in the same 20 infants at birth and through 6 months of age. DPOAE STCs
      changed little from birth through 6 months, showing excessively narrow and sharp
      tuning throughout the test period. In contrast, several middle-ear indices at
      corresponding frequencies shifted systematically with increasing age, although
      they also remained non-adultlike at 6 months. Linear correlations were conducted
      between YR and DPOAE suppression features. Only two correlations out of 76 were
      significant, and all but three YR variables accounted for <10% of the variance in
      DPOAE suppression tuning. The strongest correlation was noted between admittance
      phase at 5700 Hz and STC tip-to-tail (R=0.49). The association between middle-ear
      variables and DPOAE suppression may be stronger during other developmental time
      periods. Study of older infants and children is needed to fully define postnatal
      immaturity of human peripheral auditory function.

PMID- 17552714
TI  - Low-frequency characteristics of human and guinea pig cochleae.
AB  - Previous physiological studies investigating the transfer of low-frequency sound
      into the cochlea have been invasive. Predictions about the human cochlea are
      based on anatomical similarities with animal cochleae but no direct comparison
      has been possible. This paper presents a noninvasive method of observing low
      frequency cochlear vibration using distortion product otoacoustic emissions
      (DPOAE) modulated by low-frequency tones. For various frequencies (15-480 Hz),
      the level was adjusted to maintain an equal DPOAE-modulation depth, interpreted
      as a constant basilar membrane displacement amplitude. The resulting modulator
      level curves from four human ears match equal-loudness contours (ISO226:2003)
      except for an irregularity consisting of a notch and a peak at 45 Hz and 60 Hz,
      respectively, suggesting a cochlear resonance. This resonator interacts with the
      middle ear stiffness. The irregularity separates two regions of the middle ear
      transfer function in humans: A slope of 12 dB/octave below the irregularity
      suggests mass-controlled impedance resulting from perilymph movement through the
      helicotrema; a 6-dB/octave slope above the irregularity suggests resistive
      cochlear impedance and the existence of a traveling wave. The results from four
      guinea pig ears showed a 6-dB/octave slope on either side of an irregularity
      around 120 Hz, and agree with published data.

PMID- 17552715
TI  - Estimating the transition bandwidth between two auditory processes: evidence for
      broadband auditory filters.
AB  - A spectral discrimination task was used to estimate the frequency range over
      which information about the temporal envelope is consolidated. The standard
      consisted of n equal intensity, random phase sinusoids, symmetrically placed
      around a signal component. The signal was an intensity increment of the central
      sinusoid, which on average was 1000 Hz. Pitch cues were degraded by randomly
      selecting the center frequency of the complex and single channel energy cues were
      degraded with a roving-level procedure. Stimulus bandwidth was controlled by
      varying the number of tones and the frequency separation between tones. For a
      fixed frequency separation, thresholds increased as n increased until a certain
      bandwidth was reached, beyond which thresholds decreased. This discontinuity in
      threshold functions suggests that different auditory processes predominate at
      different bandwidths, presumably an envelope analysis at bandwidths less than the
      breakpoint and across channel level comparisons for wider stimulus bandwidths.
      Estimates of the "transition bandwidth" for 46 listeners ranged from 100 to 1250
      Hz. The results are consistent with a peripheral filtering system having multiple
      filterbanks.

PMID- 17552716
TI  - Psychophysical estimates of level-dependent best-frequency shifts in the apical
      region of the human basilar membrane.
AB  - It is now undisputed that the best frequency (BF) of basal basilar-membrane (BM)
      sites shifts downwards as the stimulus level increases. The direction of the
      shift for apical sites is, by contrast, less well established. Auditory nerve
      studies suggest that the BF shifts in opposite directions for apical and basal BM
      sites with increasing stimulus level. This study attempts to determine if this is
      the case in humans. Psychophysical tuning curves (PTCs) were measured using
      forward masking for probe frequencies of 125, 250, 500, and 6000 Hz. The level of
      a masker tone required to just mask a fixed low-level probe tone was measured for
      different masker-probe time intervals. The duration of the intervals was adjusted
      as necessary to obtain PTCs for the widest possible range of masker levels. The
      BF was identified from function fits to the measured PTCs and it almost always
      decreased with increasing level. This result is inconsistent with most auditory
      nerve observations obtained from other mammals. Several explanations are
      discussed, including that it may be erroneous to assume that low-frequency PTCs
      reflect the tuning of apical BM sites exclusively and that the inherent frequency
      response of the inner hair cell may account for the discrepancy.

PMID- 17552717
TI  - Contralateral influences of wideband inhibition on the effect of onset asynchrony
      as a cue for auditory grouping.
AB  - Onset asynchrony is an important cue for segregating sound mixtures. A harmonic
      of a vowel that begins before the other components contributes less to vowel
      quality. This asynchrony effect can be partly reversed by accompanying the
      leading portion of the harmonic with an octave-higher captor tone. The original
      interpretation was that the captor and leading portion formed a perceptual group,
      but it has recently been shown that the captor effect depends on neither a common
      onset time nor harmonic relations with the leading portion. Instead, it has been
      proposed that the captor effect depends on wideband inhibition in the central
      auditory system. Physiological evidence suggests that such inhibition occurs both
      within and across ears. Experiment 1 compared the efficacy of a pure-tone captor
      presented in the same or opposite ear to the vowel and leading harmonic.
      Contralateral presentation was at least as effective as ipsilateral presentation.
      Experiment 2 used multicomponent captors in a more comprehensive evaluation of
      harmonic influences on captor efficacy. Three captors with different fundamental
      frequencies were used, one of which formed a consecutive harmonic series with the
      leading harmonic. All captors were equally effective, irrespective of the
      harmonic relationship. These findings support and refine the inhibitory account.

PMID- 17552718
TI  - Effects of masker-spectral variability and masker fringes in children and adults.
AB  - This study examined the degree to which masker-spectral variability contributes
      to children's susceptibility to informational masking. Listeners were younger
      children (5-7 years), older children (8-10 years), and adults (19-34 years).
      Masked thresholds were measured using a 2IFC, adaptive procedure for a 300-ms,
      1000-Hz signal presented simultaneously with (1) broadband noise, (2) a random
      frequency ten-tone complex, or (3) a fixed-frequency ten-tone complex. Maskers
      were presented at an overall level of 60 dB SPL. Thresholds were similar across
      age for the noise condition. Thresholds for most children were higher than for
      most adults, however, for both ten-tone conditions. The average difference in
      threshold between random and fixed ten-tone conditions was comparable across age,
      suggesting a similar effect of reducing masker-spectral variability in children
      and adults. Children appear more likely to be susceptible to informational
      masking than adults, however, both with and in the absence of masker-spectral
      variability. The addition of a masker fringe (delayed onset of signal relative to
      masker) provided a release from masking for fixed and random ten-tone conditions
      in all age groups, suggesting at least part of the masking observed for both ten
      tone maskers was informational.

PMID- 17552719
TI  - Binaural weighting of monaural spectral cues for sound localization.
AB  - For human listeners, cues for vertical-plane localization are provided by
      direction-dependent pinna filtering. This study quantified listeners' weighting
      of the spectral cues from each ear as a function of stimulus lateral angle,
      interaural time difference (ITD), and interaural level difference (ILD). Subjects
      indicated the apparent position of headphone-presented noise bursts synthesized
      in virtual auditory space. The synthesis filters for the two ears either
      corresponded to the same location or to two different locations separated
      vertically by 20 deg. Weighting of each ear's spectral information was determined
      by a multiple regression between the elevations to which each ear's spectrum
      corresponded and the vertical component of listeners' responses. The apparent
      horizontal source location was controlled either by choosing synthesis filters
      corresponding to locations on or 30 deg left or right of the median plane or by
      attenuating or delaying the signal at one ear. For broadband stimuli, spectral
      weighting and apparent lateral angle were determined primarily by ITD. Only for
      high-pass stimuli were weighting and lateral angle determined primarily by ILD.
      The results suggest that the weighting of monaural spectral cues and the
      perceived lateral angle of a sound source depend similarly on ITD, ILD, and
      stimulus spectral range.

PMID- 17552720
TI  - Transverse pressure distributions in a simple model ear canal occluded by a
      hearing aid test fixture.
AB  - The sound field in a model ear canal with a hearing aid test fixture has been
      investigated experimentally and theoretically. Large transverse variations of
      sound pressure level, as much as 20 dB at 8 kHz, were found across the inner face
      of the hearing aid. Variations are greatest near the outlet port of the receiver
      and the vent port. Deeper into the canal, the transverse variations are less
      significant and, at depths greater than 4 mm, only a longitudinal variation
      remains. The model canal was cylindrical, 7.5 mm diameter, and terminated with a
      Zwislocki coupler to represent absorption by the human middle ear. The outer end
      of the canal was driven by the receiver in the hearing aid test fixture, with the
      acoustic output entering the canal through a 1 mm port. The hearing aid was
      provided with a 20-mm-long vent, either 1 or 2 mm in diameter. The sound field
      inside the canal was measured using a specially designed 0.2-mm-diam probe
      microphone [Daigle and Stinson, J. Acoust. Soc. Am. 116, 2618 (2004)]. In
      parallel, calculations of the interior sound field were performed using a
      boundary element technique and found to agree well with measurements.

PMID- 17552721
TI  - Focused intracochlear electric stimulation with phased array channels.
AB  - A method is described for producing focused intracochlear electric stimulation
      using an array of N electrodes. For each electrode site, N weights are computed
      that define the ratios of positive and negative electrode currents required to
      produce cancellation of the voltage within scala tympani at all of the N-1 other
      sites. Multiple sites can be stimulated simultaneously by superposition of their
      respective current vectors. The method allows N independent stimulus waveforms to
      be delivered to each of the N electrode sites without spatial overlap. Channel
      interaction from current spread associated with monopolar stimulation is
      substantially eliminated. The method operates by inverting the spread functions
      of individual monopoles as measured with the other electrodes. The method was
      implemented and validated with data from three human subjects implanted with 22
      electrode perimodiolar arrays. Results indicate that (1) focusing is realizable
      with realistic precision; (2) focusing comes at the cost of increased total
      stimulation current; (3) uncanceled voltages that arise beyond the ends of the
      array are weak except when stimulating the two end channels; and (4) close
      perimodiolar positioning of the electrodes may be important for minimizing
      stimulation current and sensitivity to measurement errors.

PMID- 17552722
TI  - Improved speech recognition in noise in simulated binaurally combined acoustic
      and electric stimulation.
AB  - Speech recognition in noise improves with combined acoustic and electric
      stimulation compared to electric stimulation alone [Kong et al., J. Acoust. Soc.
      Am. 117, 1351-1361 (2005)]. Here the contribution of fundamental frequency (F0)
      and low-frequency phonetic cues to speech recognition in combined hearing was
      investigated. Normal-hearing listeners heard vocoded speech in one ear and low
      pass (LP) filtered speech in the other. Three listening conditions (vocode-alone,
      LP-alone, combined) were investigated. Target speech (average F0=120 Hz) was
      mixed with a time-reversed masker (average F0=172 Hz) at three signal-to-noise
      ratios (SNRs). LP speech aided performance at all SNRs. Low-frequency phonetic
      cues were then removed by replacing the LP speech with a LP equal-amplitude
      harmonic complex, frequency and amplitude modulated by the F0 and temporal
      envelope of voiced segments of the target. The combined hearing advantage
      disappeared at 10 and 15 dB SNR, but persisted at 5 dB SNR. A similar finding
      occurred when, additionally, F0 contour cues were removed. These results are
      consistent with a role for low-frequency phonetic cues, but not with a
      combination of F0 information between the two ears. The enhanced performance at 5
      dB SNR with F0 contour cues absent suggests that voicing or glimpsing cues may be
      responsible for the combined hearing benefit.

PMID- 17552723
TI  - Numerical simulation of turbulence transition and sound radiation for flow
      through a rigid glottal model.
AB  - Large eddy simulation (LES)-based computational aeroacoustics techniques were
      applied to a static model of the human glottis, idealized here as a planar
      channel with an orifice, to study flow-acoustic interactions related to speech.
      Rigid models of both converging and diverging glottal passages, each featuring a
      20 deg included angle and a minimal glottal diameter of 0.04 cm, with an imposed
      transglottal pressure of 15 cm H2O, were studied. The Favre-filtered compressible
      Navier-Stokes equations were integrated for this low-Mach-number flow using an
      additive semi-implicit Runge-Kutta method and a high-order compact finite
      difference scheme with characteristic-based nonreflecting boundary conditions and
      a multiblock approach. Flow asymmetries related to the Coanda effect and
      transition to turbulence, as well as the far-field sound, were captured. Acoustic
      analogy-based far-field sound predictions were compared with direct simulations
      and showed that dipole sources, arising from unsteady flow forces exerted on the
      glottal walls, are primarily responsible for the tonal sound observed in the
      divergent glottis case.

PMID- 17552724
TI  - An articulatory basis for the labial-to-coronal effect: /pata/ seems a more
      stable articulatory pattern than /tapa/.
AB  - This paper investigates the coordination between the jaw, the tongue tip, and the
      lower lip during repetition with rate increase of labial-to-coronal (L(a)C(o))
      consonant-vowel-consonant-vowel disyllables (e.g., /pata/) and coronal-to-labial
      (C(o)L(a)) ones (e.g., /tapa/) by French speakers. For the two types of
      disyllables: (1) the speeding process induces a shift from two jaw cycles per
      disyllable to a single cycle; (2) this shift modifies the coordination between
      the jaw and the constrictors, and (3) comes with a progression toward either a
      L(a)C(o) attractor [e.g., (/pata/ or /tapa/) --> /pata/ --> /pta/] or a C(o)L(a)
      one (e.g., /pata/ or /tapa/ --> /tapa/ --> /tpa/). Yet, (4) the L(a)C(o)
      attractor is clearly favored regardless of the initial sequencing. These results
      are interpreted as evidence that a L(a)C(o) CVCV disyllable could be a more
      stable coordinative pattern for the lip-tongue-jaw motor system than a C(o)L(a)
      one. They are discussed in relation with the so-called LC effect that is the
      preference for L(a)C(o) associations rather than C(o)L(a) ones in CV.CV
      disyllables in both world languages and infants' first words.

PMID- 17552725
TI  - The effects of prosodic boundaries on nasality in Taiwan Min.
AB  - This study explores the effects of prosodic boundaries on nasality at
      intonational phrase, word, and syllable boundaries. The subjects were recorded
      saying phrases that contained a syllable-final nasal consonant followed by a
      syllable-initial stop. The timing, duration, and magnitude of the nasal airflows
      measured were used to determine the extent of nasality across boundaries. Nasal
      amplitudes were found to vary in a speaker-dependent manner among boundary types.
      However, the patterns of nasal contours and temporal aspects of the airflow
      parameters consistently varied with boundary type across all the speakers. In
      general, the duration of nasal airflow and nasal plateau were the longest at the
      intonational phrase boundary, followed by word boundary and then syllable
      boundary. In addition to the hierarchical influence of boundary strength, there
      were unique phonetic markings associated with individual boundaries. In
      particular, two nasal rises interrupted by nasal inhalation occurred only across
      an intonation phrase boundary. Also, unexpectedly, a word boundary was marked by
      the longest postboundary vowel, whereas a syllable boundary was marked with the
      shortest nasal duration. The results here support the hierarchical effect of
      boundary on both domain-edge strengthening and cross-boundary coarticulation.

PMID- 17552726
TI  - Time dependence of vocal tract modes during production of vowels and vowel
      sequences.
AB  - Vocal tract shaping patterns based on articulatory fleshpoint data from four
      speakers in the University of Wisconsin x-ray microbeam (XRMB) database [J.
      Westbury, UW-Madison, (1994)] were determined with a principal component analysis
      (PCA). Midsagittal cross-distance functions representative of approximately the
      front 6 cm of the oral cavity for each of 11 vowels and vowel-vowel (VV)
      sequences were obtained from the pellet positions and the hard palate profile for
      the four speakers. A PCA was independently performed on each speaker's set of
      cross-distance functions representing static vowels only, and again with time
      dependent cross-distance functions representing vowels and VV sequences. In all
      cases, results indicated that the first two orthogonal components (referred to as
      modes) accounted for more than 97% of the variance in each speaker's set of cross
      distance functions. In addition, the shape of each mode was shown to be similar
      across the speakers suggesting that the modes represent common patterns of vocal
      tract deformation. Plots of the resulting time-dependent coefficient records
      showed that the four speakers activated each mode similarly during production of
      the vowel sequences. Finally, a procedure was described for using the time
      dependent mode coefficients obtained from the XRMB data as input for an area
      function model of the vocal tract.

PMID- 17552727
TI  - Interactions of speaking condition and auditory feedback on vowel production in
      postlingually deaf adults with cochlear implants.
AB  - This study investigates the effects of speaking condition and auditory feedback
      on vowel production by postlingually deafened adults. Thirteen cochlear implant
      users produced repetitions of nine American English vowels prior to implantation,
      and at one month and one year after implantation. There were three speaking
      conditions (clear, normal, and fast), and two feedback conditions after
      implantation (implant processor turned on and off). Ten normal-hearing controls
      were also recorded once. Vowel contrasts in the formant space (expressed in mels)
      were larger in the clear than in the fast condition, both for controls and for
      implant users at all three time samples. Implant users also produced differences
      in duration between clear and fast conditions that were in the range of those
      obtained from the controls. In agreement with prior work, the implant users had
      contrast values lower than did the controls. The implant users' contrasts were
      larger with hearing on than off and improved from one month to one year
      postimplant. Because the controls and implant users responded similarly to a
      change in speaking condition, it is inferred that auditory feedback, although
      demonstrably important for maintaining normative values of vowel contrasts, is
      not needed to maintain the distinctiveness of those contrasts in different
      speaking conditions.

PMID- 17552728
TI  - The effect of emphatic stress on consonant vowel coarticulation.
AB  - This study assessed the acoustic coarticulatory effects of phrasal accent on
      [V1.CV2] sequences, when separately applied to V1 or V2, surrounding the voiced
      stops [b], [d], and [g]. Three adult speakers each produced 360 tokens (six V1
      contexts x ten V2 contexts x three stops x two emphasis conditions). Realizing
      that anticipatory coarticulation of V2 onto the intervocalic C can be influenced
      by prosodic effects, as well as by vowel context effects, a modified locus
      equation regression metric was used to isolate the effect of phrasal accent on
      consonantal F2 onsets, independently of prosodically induced vowel expansion
      effects. The analyses revealed two main emphasis-dependent effects: systematic
      differences in F2 onset values and the expected expansion of vowel space. By
      accounting for the confounding variable of stress-induced vowel space expansion,
      a small but consistent coarticulatory effect of emphatic stress on the consonant
      was uncovered in lingually produced stops, but absent in labial stops. Formant
      calculations based on tube models indicated similarly increased F2 onsets when
      stressed /d/ and /g/ were simulated with deeper occlusions resulting from more
      forceful closure movements during phrasal accented speech.

PMID- 17552729
TI  - Plasticity in vowel perception and production: a study of accent change in young
      adults.
AB  - This study investigated changes in vowel production and perception among
      university students from the north of England, as individuals adapt their accent
      from regional to educated norms. Subjects were tested in their production and
      perception at regular intervals over a period of 2 years: before beginning
      university, 3 months later, and at the end of their first and second years at
      university. At each testing session, subjects were recorded reading a set of
      experimental words and a short passage. Subjects also completed two perceptual
      tasks; they chose best exemplar locations for vowels embedded in either northern
      or southern English accented carrier sentences and identified words in noise
      spoken with either a northern or southern English accent. The results
      demonstrated that subjects at a late stage in their language development, early
      adulthood, changed their spoken accent after attending university. There were no
      reliable changes in perception over time, but there was evidence for a between
      subjects link between production and perception; subjects chose similar vowels to
      the ones they produced, and subjects who had a more southern English accent were
      better at identifying southern English speech in noise.

PMID- 17552730
TI  - Spectral weighting strategies for sentences measured by a correlational method.
AB  - Listeners' ability to understand speech in adverse listening conditions is
      partially due to the redundant nature of speech. Natural redundancies are often
      lost or altered when speech is filtered, such as done in AI/SII experiments. It
      is important to study how listeners recognize speech when the speech signal is
      unfiltered and the entire broadband spectrum is present. A correlational method
      [R. A. Lutfi, J. Acoust. Soc. Am. 97, 1333-1334 (1995); V. M. Richards and S.
      Zhu, J. Acoust. Soc. Am. 95, 423-424 (1994)] has been used to determine how
      listeners use spectral cues to perceive nonsense syllables when the full speech
      spectrum is present [K. A. Doherty and C. W. Turner, J. Acoust. Soc. Am. 100,
      3769-3773 (1996); C. W. Turner et al., J. Acoust. Soc. Am. 104, 1580-1585
      (1998)]. The experiments in this study measured spectral-weighting strategies for
      more naturally occurring speech stimuli, specifically sentences, using a
      correlational method for normal-hearing listeners. Results indicate that
      listeners placed the greatest weight on spectral information within bands 2 and 5
      (562-1113 and 2807-11,000 Hz), respectively. Spectral-weighting strategies for
      sentences were also compared to weighting strategies for nonsense syllables
      measured in a previous study (C. W. Turner et al., 1998). Spectral-weighting
      strategies for sentences were different from those reported for nonsense
      syllables.

PMID- 17552731
TI  - Training native English speakers to identify Japanese vowel length contrast with
      sentences at varied speaking rates.
AB  - Native English speakers were trained to identify Japanese vowel length in three
      types of training differing in sentential speaking rate: slow-only, fast-only,
      and slow-fast. Following Pisoni and Lively's high phonetic variability hypothesis
      [Pisoni, D. B., and Lively, S. E., Speech Perception and Linguistic Experience,
      433-459 (1995)], higher stimulus variability by means of training with two rates
      was hypothesized to aid learners in adapting to speech rate variation more
      effectively than training with only one rate. Trained participants identified the
      length of the second vowel of disyllables, short or long, embedded in a sentence
      of the respective rate, and received immediate feedback. The three trained
      groups' abilities before and after training were examined with tests containing
      sentences of slow, normal, and fast rates, and were compared with those of a
      control that was not trained. A robust effect of slow-fast training, a marginal
      effect of slow-only training, but no significant effect of fast-only training
      were found in the overall test scores. Slow-fast and slow-only training showed
      small advantages over fast-only training on the fast-rate test scores, while
      effects for all three training types were found on the slow- and normal-rate test
      scores. The degree to which the results support the high phonetic variability
      hypothesis is discussed.

PMID- 17552732
TI  - Training humans in non-native phoneme perception using a monkey psychoacoustic
      procedure.
AB  - Humans were trained to categorize problem non-native phonemes using an animal
      psychoacoustic procedure that trains monkeys to greater than 90% correct in
      phoneme identification [Sinnott and Gilmore, Percept. Psychophys. 66, 1341-1350
      (2004)]. This procedure uses a manual left versus right response on a lever, a
      continuously repeated stimulus on each trial, extensive feedback for errors in
      the form of a repeated correction procedure, and training until asymptotic levels
      of performance. Here, Japanese listeners categorized the English liquid contrast
      /r-l/, and English listeners categorized the Middle Eastern dental-retroflex
      contrast /d-D/. Consonant-vowel stimuli were constructed using four talkers and
      four vowels. Native listeners and phoneme contrasts familiar to all listeners
      were included as controls. Responses were analyzed using percent correct,
      response time, and vowel context effects as measures. All measures indicated
      nativelike Japanese perception of /r-l/ after 32 daily training sessions, but
      this was not the case for English perception of /d-D/. Results are related to the
      concept of "robust" (more easily recovered) versus "fragile" (more easily lost)
      phonetic contrasts [Burnham, Appl. Psycholing. 7, 207-240 (1986)].

PMID- 17552734
TI  - Vocal tract length perturbation and its application to male-female vocal tract
      shape conversion.
AB  - An alternative and complete derivation of the vocal tract length sensitivity
      function, which is an equation for finding a change in formant frequency due to
      perturbation of the vocal tract length [Fant, Quarterly Progress and Status Rep.
      No. 4, Speech Transmission Laboratory, Kungliga Teknisha Hogskolan, Stockholm,
      1975, pp. 1-14] is presented. It is based on the adiabatic invariance of the
      vocal tract as an acoustic resonator and on the radiation pressure on the wall
      and at the exit of the vocal tract. An algorithm for tuning the vocal tract shape
      to match the formant frequencies to target values, such as those of a recorded
      speech signal, which was proposed in Story [J. Acoust. Soc. Am. 119, 715-718
      (2006)], is extended so that the vocal tract length can also be changed.
      Numerical simulation of this extended algorithm shows that it can successfully
      convert between the vocal tract shapes of a male and a female for each of five
      Japanese vowels.

PMID- 17552733
TI  - Simulation and analysis of nasalized vowels based on magnetic resonance imaging
      data.
AB  - In this study, vocal tract area functions for one American English speaker,
      recorded using magnetic resonance imaging, were used to simulate and analyze the
      acoustics of vowel nasalization. Computer vocal tract models and susceptance
      plots were used to study the three most important sources of acoustic variability
      involved in the production of nasalized vowels: velar coupling area, asymmetry of
      nasal passages, and the sinus cavities. Analysis of the susceptance plots of the
      pharyngeal and oral cavities, -(B(p)+B(o)), and the nasal cavity, B(n), helped in
      understanding the movement of poles and zeros with varying coupling areas.
      Simulations using two nasal passages clearly showed the introduction of extra
      pole-zero pairs due to the asymmetry between the passages. Simulations with the
      inclusion of maxillary and sphenoidal sinuses showed that each sinus can
      potentially introduce one pole-zero pair in the spectrum. Further, the right
      maxillary sinus introduced a pole-zero pair at the lowest frequency. The
      effective frequencies of these poles and zeros due to the sinuses in the sum of
      the oral and nasal cavity outputs changes with a change in the configuration of
      the oral cavity, which may happen due to a change in the coupling area, or in the
      vowel being articulated.

PMID- 17552735
TI  - Speech enhancement using the modified phase-opponency model.
AB  - In this paper we present a model called the Modified Phase-Opponency (MPO) model
      for single-channel speech enhancement when the speech is corrupted by additive
      noise. The MPO model is based on the auditory PO model, proposed for detection of
      tones in noise. The PO model includes a physiologically realistic mechanism for
      processing the information in neural discharge times and exploits the frequency
      dependent phase properties of the tuned filters in the auditory periphery by
      using a cross-auditory-nerve-fiber coincidence detection for extracting temporal
      cues. The MPO model alters the components of the PO model such that the basic
      functionality of the PO model is maintained but the properties of the model can
      be analyzed and modified independently. The MPO-based speech enhancement scheme
      does not need to estimate the noise characteristics nor does it assume that the
      noise satisfies any statistical model. The MPO technique leads to the lowest
      value of the LPC-based objective measures and the highest value of the perceptual
      evaluation of speech quality measure compared to other methods when the speech
      signals are corrupted by fluctuating noise. Combining the MPO speech enhancement
      technique with our aperiodicity, periodicity, and pitch detector further improves
      its performance.

PMID- 17552736
TI  - Violin f-hole contribution to far-field radiation via patch near-field acoustical
      holography.
AB  - The violin radiates either from dual ports (f-holes) or via surface motion of the
      corpus (top+ribs+back), with no clear delineation between these sources.
      Combining "patch" near-field acoustical holography over just the f-hole region of
      a violin with far-field radiativity measurements over a sphere, it was possible
      to separate f-hole from surface motion contributions to the total radiation of
      the corpus below 2.6 kHz. A0, the Helmholtz-like lowest cavity resonance,
      radiated essentially entirely through the f-holes as expected while A1, the first
      longitudinal cavity mode with a node at the f-holes, had no significant f-hole
      radiation. The observed A1 radiation comes from an indirect radiation mechanism,
      induced corpus motion approximately mirroring the cavity pressure profile seen
      for violinlike bowed string instruments across a wide range of sizes. The first
      estimates of the fraction of radiation from the f-holes F(f) indicate that some
      low frequency corpus modes thought to radiate only via surface motion (notably
      the first corpus bending modes) had significant radiation through the f-holes, in
      agreement with net volume changes estimated from experimental modal analysis.
      F(f) generally trended lower with increasing frequency, following corpus mobility
      decreases. The f-hole directivity (top/back radiativity ratio) was generally
      higher than whole-violin directivity.

PMID- 17552737
TI  - Three-dimensional finite element modeling of guided ultrasound wave propagation
      in intact and healing long bones.
AB  - The use of guided waves has recently drawn significant interest in the ultrasonic
      characterization of bone aiming at supplementing the information provided by
      traditional velocity measurements. This work presents a three-dimensional finite
      element study of guided wave propagation in intact and healing bones. A model of
      the fracture callus was constructed and the healing course was simulated as a
      three-stage process. The dispersion of guided modes generated by a broadband 1
      MHz excitation was represented in the time-frequency domain. Wave propagation in
      the intact bone model was first investigated and comparisons were then made with
      a simplified geometry using analytical dispersion curves of the tube modes. Then,
      the effect of callus consolidation on the propagation characteristics was
      examined. It was shown that the dispersion of guided waves was significantly
      influenced by the irregularity and anisotropy of the bone. Also, guided waves
      were sensitive to material and geometrical changes that take place during
      healing. Conversely, when the first-arriving signal at the receiver corresponded
      to a nondispersive lateral wave, its propagation velocity was almost unaffected
      by the elastic symmetry and geometry of the bone and also could not characterize
      the callus tissue throughout its thickness. In conclusion, guided waves can
      enhance the capabilities of ultrasonic evaluation.

PMID- 17552738
TI  - Call repertoire of infant African elephants: first insights into the early vocal
      ontogeny.
AB  - African savannah elephants (Loxodonta africana) have a complex acoustic
      communication system, but very little is known about their vocal ontogeny. A
      first approach in ontogenetic studies is to define the call repertoire of
      specific age groups. Twelve hundred calls of 11 infant elephants from neonatal to
      18 months of age recorded at the Vienna Zoo in Austria and at the Daphne
      Sheldrick's orphanage at the Nairobi National Park, Kenya were analyzed. Six call
      types were structurally distinguished: the rumble, the bark, the grunt, the roar
      (subdivided into a noisy-, tonal-, and mixed-roar), the snort, and the trumpet.
      Generally, within-call-type variation was high in all individuals. In contrast to
      adult elephants, the infants showed no gender-dependent variation in the
      structure or in the number of call types produced. Male infants, however, were
      more vocally adamant in their suckle behavior than females. These results give a
      first insight to the early vocal ontogeny and should promote further ontogenetic
      studies on elephants. Due to their vocal learning ability in combination with the
      complex fission-fusion society, elephants could be an interesting model to study
      the role of imitation in the vocal ontogeny of a nonprimate terrestrial mammal.

PMID- 17552739
TI  - Caller sex and orientation influence spectral characteristics of "two-voice"
      stereotyped calls produced by free-ranging killer whales.
AB  - This study investigates how particular received spectral characteristics of
      stereotyped calls of sexually dimorphic adult killer whales may be influenced by
      caller sex, orientation, and range. Calls were ascribed to individuals during
      natural behavior using a towed beamforming array. The fundamental frequency of
      both high-frequency and low-frequency components did not differ consistently by
      sex. The ratio of peak energy within the fundamental of the high-frequency
      component relative to summed peak energy in the first two low-frequency component
      harmonics, and the number of modulation bands off the high-frequency component,
      were significantly greater when whales were oriented towards the array, while
      range and adult sex had little effect. In contrast, the ratio of peak energy in
      the first versus second harmonics of the low-frequency component was greater in
      calls produced by adult females than adult males, while orientation and range had
      little effect. The dispersion of energy across harmonics has been shown to relate
      to body size or sex in terrestrial species, but pressure effects during diving
      are thought to make such a signal unreliable in diving animals. The observed
      spectral differences by signaler sex and orientation suggest that these types of
      information may be transmitted acoustically by freely diving killer whales.

PMID- 17552740
TI  - Echolocation click sounds from wild inshore finless porpoise (Neophocaena
      phocaenoides sunameri) with comparisons to the sonar of riverine N. p.
      asiaeorientalis.
AB  - Acoustic signals from wild Neophocaena phocaenoides sunameri were recorded in the
      waters off Liao-dong-wan Bay located in Bohai Sea, China. Signal analysis shows
      that N. p. sunameri produced "typical" phocoenid clicks. The peak frequencies
      f(p) of clicks ranged from 113 to 131 kHz with an average of 121+/-3.78 kHz
      (n=71). The 3 dB bandwidths delta f ranged from 10.9 to 25.0 kHz with an average
      of 17.5+/-3.30 kHz. The signal durations delta t ranged from 56 to 109 micros
      with an average 80+/-11.49 micros. The number of cycles N(c) ranged from 7 to 13
      with an average of 9+/-1.48. With increasing peak frequency there was a faint
      tendency of decrease in bandwidth, which implies a nonconstant value of
      f(p)/delta f. On occasion there were some click trains with faint click energy
      presenting below 70 kHz, however, it was possibly introduced by interference
      effect from multiple pulses structures. The acoustic parameters of the clicks
      were compared between the investigated population and a riverine population of
      finless porpoise.

PMID- 17552741
TI  - Do acoustic features of lion, Panthera leo, roars reflect sex and male condition?
AB  - Long distance calls function to regulate intergroup spacing, attract mating
      partners, and/or repel competitors. Therefore, they may not only provide
      information about the sex (if both sexes are calling) but also about the
      condition of the caller. This paper provides a description of the acoustic
      features of roars recorded from 18 male and 6 female lions (Panthera leo) living
      in the Serengeti National park, Tanzania. After analyzing whether these roars
      differ between the sexes, tests whether male roars may function as indicators of
      their fighting ability or condition were conducted. Therefore, call
      characteristics were tested for relation to anatomical features as size, mane
      color, or mane length. Call characteristics included acoustic parameters that
      previously had been implied as indicators of size and fighting ability, e.g.,
      call length, fundamental frequency, and peak frequency. The analysis revealed
      differences in relation to sex, which were entirely explained by variation in
      body size. No evidence that acoustic variables were related to male condition was
      found, indicating that sexual selection might only be a weak force modulating the
      lion's roar. Instead, lion roars may have mainly been selected to effectively
      advertise territorial boundaries.

PMID- 17552743
TI  - High-frequency ultrasound backscattering by blood: analytical and semianalytical
      models of the erythrocyte cross section.
AB  - This paper proposes analytical and semianalytical models of the ultrasonic
      backscattering cross section (BCS) of various geometrical shapes mimicking a red
      blood cell (RBC) for frequencies varying from 0 to 90 MHz. By assuming the first
      order Born approximation and by modeling the shape of a RBC by a realistic
      biconcave volume, different scattering behaviors were identified for increasing
      frequencies. For frequencies below 18 MHz, a RBC can be considered a Rayleigh
      scatterer. For frequencies less than 39 MHz, the general concept of acoustic
      inertia tensor is introduced to describe the variation of the BCS with the
      frequency and the incidence direction. For frequencies below 90 MHz, ultrasound
      backscattering by a RBC is equivalent to backscattering by a cylinder of height 2
      microm and diameter 7.8 microm. These results lay the basis of ultrasonic
      characterization of RBC aggregation by proposing a method that distinguishes the
      contribution of the individual RBC acoustical characteristics from collective
      effects, on the global blood backscattering coefficient. A new method of data
      reduction that models the frequency dependence of the ultrasonic BCS of micron
      sized weak scatterers is also proposed. Applications of this method are in tissue
      characterization as well as in hematology.

PMID- 17552744
TI  - Anisotropy of the angular distribution of fragment ions in dissociative double
      photoionization of N2O molecules in the 30-50 eV energy range.
AB  - The double photoionization of N2O molecules by linearly polarized light in the 30
      50 eV energy range has been studied by coupling ion imaging technique and
      electron-ion-ion coincidence. For the two possible dissociative processes,
      leading to N++NO+ and O++N2+, angular distributions of ionic fragments have been
      measured, finding an evident anisotropy. This indicates that the molecules ionize
      when their axis is parallel to the light polarization vector and the fragments
      are separating in a time shorter than the dication rotational period. The
      analysis of results provides, in addition to the total kinetic energy of ionic
      fragments, crucial information about the double photoionization dynamics.

PMID- 17552742
TI  - Modeling the detection range of fish by echolocating bottlenose dolphins and
      harbor porpoises.
AB  - The target strength as a function of aspect angle were measured for four species
      of fish using dolphin-like and porpoise-like echolocation signals. The polar
      diagram of target strength values measured from an energy flux density
      perspective showed considerably less fluctuation with azimuth than would a pure
      tone pulse. Using detection range data obtained from dolphin and porpoise
      echolocation experiments, the detection ranges for the Atlantic cod by
      echolocating dolphins and porpoises were calculated for three aspect angles of
      the cod. Maximum detection ranges occurred when the fish was broadside to the
      odontocete and minimum detection ranges occurred when the cod was in the tail
      aspect. Maximum and minimum detection ranges for the bottlenose dolphin in a
      noise-limited environment was calculated to be 93 and 70 m, respectively. In a
      quiet environment, maximum and minimum detection ranges for the bottlenose
      dolphin were calculated to be 173 and 107 m, respectively. The detection ranges
      for the harbor porpoise in a quiet environment were calculated to be between 15
      and 27 m. The primary reason for the large differences in detection ranges
      between both species was attributed to the 36 dB higher source level of the
      bottlenose dolphin echolocation signals.

PMID- 17552745
TI  - Role of the exchange-correlation potential in ab initio electron transport
      calculations.
AB  - The effect of the exchange-correlation potential in ab initio electron transport
      calculations is investigated by constructing optimized effective potentials using
      different energy functionals or the electron density from second-order
      perturbation theory. The authors calculate electron transmission through two
      atomic chain systems, one with charge transfer and one without. Dramatic effects
      are caused by two factors: changes in the energy gap and the self-interaction
      error. The error in conductance caused by the former is about one order of
      magnitude while that caused by the latter ranges from several times to two orders
      of magnitude, depending on the coupling strength and charge transfer. The
      implications for accurate quantum transport calculations are discussed.

PMID- 17552746
TI  - Completeness of a kinetically balanced Gaussian basis.
AB  - It is shown that the exact relativistic wave function of the ground state of H
      like ions can be expanded in a kinetically balanced even-tempered Gaussian basis.
      The error of the overlap integral between exact and approximate wave function
      depends as approximately n3/2+nu exp[-pisqrt(3/2+nu)n], with nu=-1+sqrt1-Z2/c2,
      on the size n of the basis, both for the large and the small components. Even the
      error of the energy has essentially the same dependence on n and decays only
      slightly slower than its nonrelativistic counterpart, which goes as approximately
      n3/2 exp[-pisqrt3n/2].

PMID- 17552747
TI  - Lagrangian approach to molecular vibrational Raman intensities using time
      dependent hybrid density functional theory.
AB  - The authors propose a new route to vibrational Raman intensities based on
      analytical derivatives of a fully variational polarizability Lagrangian. The
      Lagrangian is constructed to recover the negative frequency-dependent
      polarizability of time-dependent Hartree-Fock or adiabatic (hybrid) density
      functional theory at its stationary point. By virtue of the variational
      principle, first-order polarizability derivatives can be computed without using
      derivative molecular orbital coefficients. As a result, the intensities of all
      Raman-active modes within the double harmonic approximation are obtained at
      approximately the same cost as the frequency-dependent polarizability itself.
      This corresponds to a reduction of the scaling of computational expense by one
      power of the system size compared to a force constant calculation and to previous
      implementations. Since the Raman intensity calculation is independent of the
      harmonic force constant calculation more, computationally demanding density
      functionals or basis sets may be used to compute the polarizability gradient
      without much affecting the total time required to compute a Raman spectrum. As
      illustrated for fullerene C60, the present approach considerably extends the
      domain of molecular vibrational Raman calculations at the (hybrid) density
      functional level. The accuracy of absolute and relative Raman intensities of
      benzene obtained using the PBE0 hybrid functional is assessed by comparison with
      experiment.

PMID- 17552748
TI  - Vibrational excitation energies from vibrational coupled cluster response theory.
AB  - Response theory in the context of vibrational coupled cluster (VCC) theory is
      introduced and used to obtain vibrational excitation energies. The relation to
      the vibrational configuration interaction (VCI) approach is described, and the
      increase in accuracy of VCC response energies relative to VCI energies is
      discussed theoretically in terms of a perturbational order expansion and
      demonstrated numerically. To illustrate the theory, a pilot implementation is
      used to obtain anharmonic vibrational frequencies for fundamental, first overtone
      and combination excitations of formaldehyde as well as for the fundamental
      transitions of ethylene.

PMID- 17552749
TI  - Anharmonic properties of the vibrational quantum computer.
AB  - We developed an efficient approach to study the coherent control of vibrational
      state-to-state transitions. The approximations employed in our model are valid in
      the regime of the low vibrational excitation specific to the vibrational quantum
      computer. Using this approach we explored how the vibrational properties of a two
      qubit system affect the accuracy of subpicosecond quantum gates. The optimal
      control theory and numerical propagation of laser-driven vibrational wave packets
      were employed. The focus was on understanding the effect of the three
      anharmonicity parameters of the system. In the three-dimensional anharmonicity
      parameter space we identified several spots of high fidelity separated by low
      fidelity planar regions. The seemingly complicated picture is explained in terms
      of interferences between different state-to-state transitions. Very general
      analytic relationships between the anharmonicity parameters and the frequencies
      are derived to describe the observed features. Geometrically, these expressions
      represent planes in the three-dimensional anharmonicity parameter space. Results
      of this work should help to choose a suitable candidate molecule for the
      practical implementation of the vibrational two-qubit system.

PMID- 17552750
TI  - A simple and efficient evolution operator for time-dependent Hamiltonians: the
      Taylor expansion.
AB  - No compact expression of the evolution operator is known when the Hamiltonian
      operator is time dependent, like when Hamiltonian operators describe, in a
      semiclassical limit, the interaction of a molecule with an electric field. It is
      well known that Magnus [N. Magnus, Commun. Pure Appl. Math. 7, 649 (1954)] has
      derived a formal expression where the evolution operator is expressed as an
      exponential of an operator defined as a series. In spite of its formal
      simplicity, it turns out to be difficult to use at high orders. For numerical
      purposes, approximate methods such as "Runge-Kutta" or "split operator" are often
      used usually, however, to a small order (<5), so that only small time steps,
      about one-tenth or one-hundredth of the field cycle, are acceptable. Moreover,
      concerning the latter method, split operator, it is only very efficient when a
      diagonal representation of the kinetic energy operator is known. The Taylor
      expansion of the evolution operator or the wave function about the initial time
      provides an alternative approach, which is very simple to implement and, unlike
      split operator, without restrictions on the Hamiltonian. In addition, relatively
      large time steps (up to the field cycle) can be used. A two-level model and a
      propagation of a Gaussian wave packet in a harmonic potential illustrate the
      efficiency of the Taylor expansion. Finally, the calculation of the time-averaged
      absorbed energy in fluoroproprene provides a realistic application of our method.

PMID- 17552751
TI  - Monte Carlo approach to the decay rate of a metastable system with an arbitrarily
      shaped barrier.
AB  - A path integral Monte Carlo method based on the fast-Fourier transform technique
      combined with the important sampling method is proposed to calculate the decay
      rate of a metastable quantum system with an arbitrary shape of a potential
      barrier. The contribution of all fluctuation actions is included which can be
      used to check the accuracy of the usual steepest-descent approximation, namely,
      the perturbation expansion of potential. The analytical approximation is found to
      produce the decay rate of a particle in a cubic potential being about 20% larger
      than the Monte Carlo data at the crossover temperature. This disagreement
      increases with increasing complexity of the potential shape. We also demonstrate
      via Langevin simulation that the postsaddle potential influences strongly upon
      the classical escape rate.

PMID- 17552752
TI  - Derivatives of the polarization propagator including orbital relaxation effects.
AB  - In this article, we relate derivatives of the polarization propagator used in
      many-body theory to the nonlinear (quadratic) polarization propagator, and we
      relate derivatives of the quadratic polarization propagator to the nonlinear
      propagator of the next higher order, the cubic polarization propagator. We
      restrict the analysis to differentiation with respect to parameters eta for which
      the derivative of the Hamiltonian can be written as a sum of one-electron
      operators. Geometrical derivatives are obtained by specializing to the parameter
      eta to the alpha coordinate of nucleus I. We treat orbital relaxation explicitly
      by allowing for the eta dependence of creation and annihilation operators in the
      propagators. This treatment entails an extension of the geometrical derivative
      relations among response functions proven by Olsen and Jorgensen [J. Chem. Phys.
      82, 3235 (1985)], because the propagator derivatives may involve changes in the
      one-electron orbitals that do not appear in the susceptibility derivatives. These
      results underlie the relations between Raman intensities and electric-field
      shielding tensors, which have been explained in terms of nonlocal polarizability
      and hyperpolarizability densities. The results suggest an alternative
      computational route to geometrical or other derivatives of both linear- and
      nonlinear-response functions: these derivatives can be evaluated without
      numerical differentiation, directly from the propagator of the next higher order.

PMID- 17552753
TI  - Local effective potential theory: nonuniqueness of potential and wave function.
AB  - In local effective potential energy theories such as the Hohenberg-Kohn-Sham
      density functional theory (HKS-DFT) and quantal density functional theory (Q
      DFT), electronic systems in their ground or excited states are mapped to model
      systems of noninteracting fermions with equivalent density. From these models,
      the equivalent total energy and ionization potential are also obtained. This
      paper concerns (i) the nonuniqueness of the local effective potential energy
      function of the model system in the mapping from a nondegenerate ground state,
      (ii) the nonuniqueness of the local effective potential energy function in the
      mapping from a nondegenerate excited state, and (iii) in the mapping to a model
      system in an excited state, the nonuniqueness of the model system wave function.
      According to nondegenerate ground state HKS-DFT, there exists only one local
      effective potential energy function, obtained as the functional derivative of the
      unique ground state energy functional, that can generate the ground state
      density. Since the theorems of ground state HKS-DFT cannot be generalized to
      nondegenerate excited states, there could exist different local potential energy
      functions that generate the excited state density. The constrained-search version
      of HKS-DFT selects one of these functions as the functional derivative of a
      bidensity energy functional. In this paper, the authors show via Q-DFT that there
      exist an infinite number of local potential energy functions that can generate
      both the nondegenerate ground and excited state densities of an interacting
      system. This is accomplished by constructing model systems in configurations
      different from those of the interacting system. Further, they prove that the
      difference between the various potential energy functions lies solely in their
      correlation-kinetic contributions. The component of these functions due to the
      Pauli exclusion principle and Coulomb repulsion remains the same. The existence
      of the different potential energy functions as viewed from the perspective of Q
      DFT reaffirms that there can be no equivalent to the ground state HKS-DFT
      theorems for excited states. Additionally, the lack of such theorems for excited
      states is attributable to correlation-kinetic effects. Finally, they show that in
      the mapping to a model system in an excited state, there is a nonuniqueness of
      the model system wave function. Different wave functions lead to the same
      density, each thereby satisfying the sole requirement of reproducing the
      interacting system density. Examples of the nonuniqueness of the potential energy
      functions for the mapping from both ground and excited states and the
      nonuniqueness of the wave function are provided for the exactly solvable Hooke's
      atom. The work of others is also discussed.

PMID- 17552754
TI  - Hydrogen bonding definitions and dynamics in liquid water.
AB  - X-ray and neutron diffractions, vibrational spectroscopy, and x-ray Raman
      scattering and absorption experiments on water are often interpreted in terms of
      hydrogen bonding. To this end a number of geometric definitions of hydrogen
      bonding in water have been developed. While all definitions of hydrogen bonding
      are to some extent arbitrary, those involving one distance and one angle for a
      given water dimer are unnecessarily so. In this paper the authors develop a
      systematic procedure based on two-dimensional potentials of mean force for
      defining cutoffs for a given pair of distance and angular coordinates. They also
      develop an electronic structure-based definition of hydrogen bonding in liquid
      water, related to the electronic occupancy of the antibonding OH orbitals. This
      definition turns out to be reasonably compatible with one of the distance-angle
      geometric definitions. These two definitions lead to an estimate of the number of
      hydrogen bonds per molecule in liquid simple point charge/extended (SPC/E) water
      of between 3.2 and 3.4. They also used these and other hydrogen-bond definitions
      to examine the dynamics of local hydrogen-bond number fluctuations, finding an
      approximate long-time decay constant for SPC/E water of between 0.8 and 0.9 ps,
      which corresponds to the time scale for local structural relaxation.

PMID- 17552755
TI  - Canonical averaging in the second order quantized Hamilton dynamics by extension
      of the coherent state thermodynamics of the harmonic oscillator.
AB  - A conceptually simple approximation to quantum mechanics, quantized Hamilton
      dynamics (QHD) includes zero-point energy, tunneling, dephasing, and other
      important quantum effects in a classical-like description. The hierarchy of
      coupled differential equations describing the time evolution of observables in
      QHD can be mapped in the second order onto a classical system with double the
      dimensionality of the original system. While QHD excels at dynamics with a single
      initial condition, the correct method for generating thermal initial conditions
      in QHD remains an open question. Using the coherent state representation of
      thermodynamics of the harmonic oscillator (HO) [Schnack, Europhys. Lett. 45, 647
      (1999)], we develop canonical averaging for the second order QHD [Prezhdo, J.
      Chem. Phys. 117, 2995 (2002)]. The methodology is exact for the free particle and
      HO, and shows good agreement with quantum results for a variety of quartic
      potentials.

PMID- 17552756
TI  - Ab initio potential energy surface and spectrum of the B(3Pi) state of the HeI2
      complex.
AB  - The three-dimensional interaction potential for I2(B 3Pi0u+)+He is computed using
      accurate ab initio methods and a large basis set. Scalar relativistic effects are
      accounted for by large-core relativistic pseudopotentials for the iodine atoms.
      Using multireference configuration interaction calculations with subsequent
      treatment of spin-orbit coupling, it is shown for linear and perpendicular
      structures of the complex that the interaction potential for I2(B 3Pi0u+)+He is
      very well approximated by the average of the 3A' and 3A" interaction potentials
      obtained without spin-orbit coupling. The three-dimensional 3A' and 3A"
      interaction potentials are computed at the unrestricted open-shell coupled
      cluster level of theory using large basis sets. Bound state calculations based on
      the averaged surface are carried out and binding energies, vibrationally averaged
      structures, and frequencies are determined. These results are found to be in
      excellent accord with recent experimental measurements from laser-induced
      fluorescence and action spectra of HeI2. Furthermore, in combination with a
      recent X-state potential, the spectral blueshift is obtained and compared with
      available experimental values.

PMID- 17552757
TI  - Q-branch linewidths of N2 perturbed by H2: experiments and quantum calculations
      from an ab initio potential.
AB  - In this work the authors present an experimental and theoretical study about the
      Q-branch lines' broadening coefficients of N2 perturbed by H2. Experimental
      values for these parameters have been obtained at 440 and 580 K, and quantum
      calculations have been performed using a new ab initio potential energy surface,
      obtained by quantum chemistry methods. The results of these calculations are
      compared to experimental data obtained previously at 77 and 298 K [L. Gomez et
      al., Mol. Phys. 104, 1869 (2006)] and to the present measurements. A satisfactory
      agreement is obtained for the whole range of temperatures used in the
      experiments.

PMID- 17552758
TI  - Analytic functions for the three-body potential of the helium trimer.
AB  - The three-body potential for the ground state of the helium trimer is determined
      by an extended geminal model. The basis set for the calculation is an
      uncontracted (19s,7p,6d,5f,4g,2h) set of Gaussian-type functions. Three different
      types of configurations were considered: (i) equilateral triangles, (ii) linear
      configurations with R12=R23, and (iii) a set of pseudorandom configurations. The
      interatomic distances were selected within the interval [3.0,9.0] bohrs. The
      computed points have been fitted to global potential functions. The fit is
      characterized by a maximum absolute error equal to 0.69 microEh and a mean error
      equal to -0.018 microEh.

PMID- 17552759
TI  - Five-dimensional ab initio potential energy surface and predicted infrared
      spectra of H2-CO2 van der Waals complexes.
AB  - The authors present a new five-dimensional potential energy surface for H2-CO2
      including the Q3 normal mode for the nu3 antisymmetric stretching vibration of
      the CO2 molecule. The potential energies were calculated using the supermolecular
      approach with the full counterpoise correction at the CCSD(T) level with an aug
      cc-pVTZ basis set supplemented with bond functions. The global minimum is at two
      equivalent T-shaped coplanar configurations with a well depth of 219.68 cm-1. The
      rovibrational energy levels for four species of H2-CO2 (paraH2-, orthoH2-, paraD2
      , and orthoD2-CO2) were calculated employing the discrete variable representation
      (DVR) for radial variables and finite basis representation (FBR) for angular
      variables and the Lanczos algorithm. Our calculations showed that the off
      diagonal intra- and intermolecular vibrational coupling could be neglected, and
      separation of the intramolecular vibration by averaging the total Hamiltonian
      with the wave function of a specific vibrational state of CO2 should be a good
      approximation with high accuracy. The calculated band origin shift in the
      infrared spectra in the nu3 region of CO2 is -0.113 cm-1 for paraH2-CO2 and 
      0.099 cm-1 for orthoH2-CO2, which agrees well with the observed values of -0.198
      and -0.096 cm-1. The calculated rovibrational spectra for H2-CO2 are consistent
      with the available experimental spectra. For D2-CO2, it is predicted that only a
      type transitions occur for paraD2-CO2, while both a-type and b-type transitions
      are significant for orthoD2-CO2.

PMID- 17552760
TI  - Macroscopic evidences for non-Rice-Ramsperger-Kassel effects in the reaction
      between H3O+ and D2O: the occurrence of nonstatistical isotopic branching ratio.
AB  - The dynamics of the isotopic scrambling in the energized and metastable complex
      D2O-H3O+ has been studied using classical molecular dynamics (MD) trajectories
      starting from regions of phase space corresponding to an already formed
      collisional complex. The simulations cover the range of internal energies spanned
      by gas phase collision experiments. Rate constants for the isotopic exchange and
      the complex dissociation have been computed; the isotopic branching ratio
      R=[HD2O+]/[H2DO+] has also been obtained from MD simulations and found to deviate
      substantially from an equivalent prediction based on a previously proposed
      kinetic scheme. This finding suggests the possibility that details of the
      reaction dynamics play a role in defining the isotopic branching ratio. The
      analysis of trajectory results indicated a relatively long lifetime for the
      collisional complex and the presence of multiple time scales for the exchange
      process, with a large fraction of the exchange events being separated only by a
      single oxygen-oxygen vibration or half of it. The occurrence of these fast
      consecutive jumps and their different probabilities as a function of the relative
      direction between first and second jumps suggest the presence of ballistic motion
      in the complex following each reactive event. This can be explained on the basis
      of overlapping regions in phase space and it is used to provide an explanation of
      the difference between kinetic and MD branching ratios.

PMID- 17552761
TI  - Electronic anisotropy between open shell atoms in first and second order
      perturbation theory.
AB  - The interaction between two atoms in states with nonzero electronic orbital
      angular momenta is anisotropic and can be represented by a spherical tensor
      expansion. The authors derive expressions for the first order (electrostatic) and
      second order (dispersion and induction) anisotropic interaction coefficients in
      terms of the multipole moments and dynamic polarizabilities of the atoms and show
      that a complete description of the second order interaction requires odd rank or
      "out-of-phase" polarizabilities. The authors relate the tensorial expansion
      coefficients to the adiabatic Born-Oppenheimer potentials of the molecule and
      show that there are linear, and in some cases nonlinear, constraints on the van
      der Waals coefficients of these potentials.

PMID- 17552762
TI  - On the helix-coil transition in alanine based polypeptides in gas phase.
AB  - Using multicanonical simulations, the authors study the effect of charged end
      groups on helix formation in alanine based polypeptides. They confirm earlier
      reports that neutral polyalanine exhibits a pronounced helix-coil transition in
      gas phase simulations. Introducing a charged Lys+ at the C terminal stabilizes
      the alpha helix and leads to a higher transition temperature. On the other hand,
      adding the Lys+ at the N terminal inhibits helix formation. Instead, a more
      globular structure was found. These results are in agreement with recent
      experiments on alanine based polypeptides in gas phase. They indicate that
      present force fields describe accurately the intramolecular interactions in
      proteins.

PMID- 17552763
TI  - Reagents for electrophilic amination: a quantum Monte Carlo study.
AB  - Electrophilic amination is an appealing synthetic strategy to construct carbon
      nitrogen bonds. The authors explore the use of the quantum Monte Carlo method and
      a proposed variant of the electron pair localization function--the electron pair
      localization function density--as a measure of the nucleophilicity of nitrogen
      lone pairs as a possible screening procedure for electrophilic reagents.

PMID- 17552764
TI  - Infrared spectra of the Li+-(H2)n (n=1-3) cation complexes.
AB  - The Li+-(H2)n n=1-3 complexes are investigated through infrared spectra recorded
      in the H-H stretch region (3980-4120 cm-1) and through ab initio calculations at
      the MP2/aug-cc-pVQZ level. The rotationally resolved H-H stretch band of Li+-H2
      is centered at 4053.4 cm-1 [a -108 cm-1 shift from the Q1(0) transition of H2].
      The spectrum exhibits rotational substructure consistent with the complex
      possessing a T-shaped equilibrium geometry, with the Li+ ion attached to a
      slightly perturbed H2 molecule. Around 100 rovibrational transitions belonging to
      parallel Ka=0-0, 1-1, 2-2, and 3-3 subbands are observed. The Ka=0-0 and 1-1
      transitions are fitted by a Watson A-reduced Hamiltonian yielding effective
      molecular parameters. The vibrationally averaged intermolecular separation in the
      ground vibrational state is estimated as 2.056 A increasing by 0.004 A when the
      H2 subunit is vibrationally excited. The spectroscopic data are compared to
      results from rovibrational calculations using recent three dimensional Li+-H2
      potential energy surfaces [Martinazzo et al., J. Chem. Phys. 119, 11241 (2003);
      Kraemer and Spirko, Chem. Phys. 330, 190 (2006)]. The H-H stretch band of Li+
      (H2)2, which is centered at 4055.5 cm-1 also exhibits resolved rovibrational
      structure. The spectroscopic data along with ab initio calculations support a H2
      Li+-H2 geometry, in which the two H2 molecules are disposed on opposite sides of
      the central Li+ ion. The two equivalent Li+...H2 bonds have approximately the
      same length as the intermolecular bond in Li+-H2. The Li+-(H2)3 cluster is
      predicted to possess a trigonal structure in which a central Li+ ion is
      surrounded by three equivalent H2 molecules. Its infrared spectrum features a
      broad unresolved band centered at 4060 cm-1.

PMID- 17552765
TI  - Prediction of product branching ratios in the C(3P)+C2H2-->l-C3H+H/c-C3H+H/C3+H2
      reaction using ab initio coupled clusters calculations extrapolated to the
      complete basis set combined with Rice-Ramsperger-Kassel-Marcus and radiationless
      transition theories.
AB  - Ab initio CCSD(T) calculations of intermediates and transition states on the
      singlet and triplet C3H2 potential energy surfaces extrapolated to the complete
      basis set limit are combined with statistical computations of energy-dependent
      rate constants of the C(3P)+C2H2 reaction under crossed molecular beam
      conditions. Rice-Ramsperger-Kassel-Marcus theory is applied for isomerization and
      dissociation steps within the same multiplicity and radiationless transition and
      nonadiabatic transition state theories are used for singlet-triplet intersystem
      crossing rates. The calculated rate constants are utilized to predict product
      branching ratios. The results demonstrate that, in qualitative agreement with
      available experimental data, c-C3H+H and C3+H2 are the most probable products at
      low collision energies, whereas l-C3H+H becomes dominant at higher Ec above
      approximately 25 kJ/mol.

PMID- 17552766
TI  - Photodissociation of gas-phase I3-: comprehensive understanding of nonadiabatic
      dissociation dynamics.
AB  - Photodissociation of the gas-phase tri-iodide anion, I3-, was investigated using
      photofragment time of flight (TOF) mass spectrometry combined with the core
      extraction method. An analysis of the TOF profiles provided the kinetic energy
      and angular distributions of photofragment ions and photoneutrals, from which the
      photoproduct branching fractions were determined in the excitation energy range
      of 3.26-4.27 eV. The measurement has revealed that (1) in the entire energy range
      investigated, three-body dissociation occurs preferentially as the "charge
      asymmetric" process I-(1S)+I(2P3/2)+I(2P3/2) with the yield of approximately 30%
      40%, where the excess charge is localized on the end atoms of the dissociating I3
      , and that (2) two-body dissociation via the 3Piu(0u+)<--1Sigmag+(0g+) excitation
      proceeds as I-(1S)+I2(X 1Sigmag+)/I2(A 3Pi1u) or I(2P3/2)+I2-(X 2Sigmau+) with
      the yield of approximately 60%, while that via the 1Sigmau+(0u+)<--1Sigmag+(0g+)
      excitation alternatively as I*(2P1/2)+I2-(X 2Sigmau+) or I-(1S)+I2(B 3Piu) with
      the yield of approximately 60%. Ab initio calculations including spin-orbit
      configuration interactions were also performed to gain precise information on the
      potential energy surfaces relevant to the I3- photodissociation. The calculations
      have shown the presence of conical intersections and avoided crossings located
      along the symmetric stretch coordinate near the ground-state equilibrium geometry
      of I3-, which play key roles for the two-body and the three-body product
      branching. The nonadiabatic nature of the I3- photodissociation dynamics is
      discussed by combining the experimental findings and the ab initio results.

PMID- 17552767
TI  - Tagging multiphoton ionization events by two-dimensional photoelectron
      spectroscopy.
AB  - Two-dimensional photoelectron spectroscopy has been used to supply process
      specific labels to multiphoton ionization events. Employing these tags, the
      authors can construct excitation and photoelectron spectra along predefined
      excitation routes in the neutral manifold and ionization routes to the ionic
      manifold from one single two-dimensional photoelectron spectrum. These results
      offer a novel way to elucidate the vibronic and dynamic properties of excited and
      ionic states.

PMID- 17552768
TI  - First ultraviolet absorption band of methane: an ab initio study.
AB  - Quantum mechanical calculations of the cross sections for photodissociation of
      CH4 and CD4 in the 1t2-->3s band are presented. The potential energy surfaces for
      the three states correlating with the 1 1T2 state at tetrahedral geometries are
      calculated. The elements of the (3x3) matrix representing the electronic
      Hamiltonian in the diabatic basis are expanded in powers of nuclear coordinates,
      up to the second order. The expansion coefficients are based on accurate
      multireference configuration interaction calculations. The electronically
      nonadiabatic dynamics is treated with the multiconfiguration time-dependent
      Hartree approach. All nine internal degrees of methane are included in the
      quantum dynamics simulations. The calculated cross section agrees well with
      experiment. Semiclassical calculations using the reflection principle suggest
      that the peaks in the spectrum correspond to the three adiabatic electronic
      states correlating with the 1 1T2 state at Td geometries. However, the non-Born
      Oppenheimer terms in the Hamiltonian have a strong effect on the positions of the
      peaks in the absorption spectrum. The results of semiclassical calculations,
      which neglect these terms, are therefore quite different from the accurate
      quantum results and experiment.

PMID- 17552769
TI  - Thermochemistry of new molecular species: SBr and HSBr.
AB  - Total energies, optimized geometries, and vibrational frequencies of SBr and HSBr
      have been evaluated at the coupled cluster level of theory with the correlation
      consistent basis sets. Extrapolated to the complete basis set limit and with
      corrections for core-valence, scalar relativistic, and spin-orbit effects,
      atomization energies were computed and then combined with the experimental heats
      of formation of the atomic species to generate very accurate heats of formation
      for the species SBr and HSBr. For SBr, we predict 37.45 and 36.07 kcal/mol for
      DeltaHf(0 K) and DeltaHf (298.15 K), respectively, in very good agreement with
      the inferred experimental values of 37.98 and 36.15 kcal/mol. For HSBr, the
      estimate turns out to be 10.38 and 8.29 kcal/mol for DeltaHf (0 K) and DeltaHf
      (298.15 K), respectively. Using the more recent HBrO experimental heat of
      formation at 298.15 K of Lock et al., [J. Phys. Chem. 100, 7972 (1996)] the
      inferred experimental value for HSBr is predicted to be 8.15 kcal/mol, compared
      with 8.65 kcal/mol derived from the data of Ruscic and Berkowitz [J. Chem. Phys.
      101, 7795 (1994)]. Considering the better agreement of the result with that
      predicted using the experimental value of DeltaHf(298.15 K) of Lock et al., the
      author also supports the suggestion made by Denis [J. Phys. Chem. A. 110, 5887
      (2006)] that the result of Lock et al. should be preferred over the one of Ruscic
      and Berkowitz. For DeltaHf(0 K), the author found 10.38 and 10.56 kcal/mol,
      respectively, for the theoretical and inferred experimental estimates.

PMID- 17552771
TI  - Electronic quenching of OH A 2Sigma+ radicals in single collision events with
      molecular hydrogen: quantum state distribution of the OH X 2Pi products.
AB  - We report a combined experimental and theoretical investigation of the
      nonreactive quenching channel resulting from electronic quenching of OH A 2Sigma+
      by molecular hydrogen. The experiments utilize a pump-probe scheme to determine
      the OH X 2Pi population distribution following collisional quenching in a pulsed
      supersonic expansion. The pump laser excites OH A 2Sigma+ (nu'=0, N'=0), which
      has a significantly reduced fluorescence lifetime due to quenching by H2. The
      probe laser monitors the OH X 2Pi (nu", N") population via laser-induced
      fluorescence on various A-X transitions under single collision conditions. The
      experiments reveal a high degree of rotational excitation (N") of the quenched OH
      X 2Pi products observed in nu"=1 and 2 as well as a pronounced propensity for
      quenching into the Pi(A') Lambda-doublet level. These experiments have been
      supplemented by extensive multireference, configuration-interaction calculations
      aimed at exploring the topology of the relevant potential energy surfaces.
      Electronic quenching of OH A 2Sigma+ by H2 proceeds through conical intersections
      between two potentials of A' reflection symmetry (in planar geometry) that
      correlate with the electronically excited A 2Sigma+ and ground X 2Pi states of
      OH. The conical intersections occur in high-symmetry geometries, in which the O
      side of OH points toward H2. Corroborating and extending earlier work of Hoffman
      and Yarkony [J. Chem. Phys. 113, 10091 (2000)], these calculations reveal a steep
      gradient away from the OH-H2 conical intersection as a function of both the OH
      orientation and interfragment distance. The former will give rise to a high
      degree of OH rotational excitation, as observed for the quenched OH X 2Pi
      products.

PMID- 17552770
TI  - Dissociation of carbonic acid: gas phase energetics and mechanism from ab initio
      metadynamics simulations.
AB  - A comprehensive metadynamics study of the energetics, stability, conformational
      changes, and mechanism of dissociation of gas phase carbonic acid, H2CO3, yields
      significant new insight into these reactions. The equilibrium geometries,
      vibrational frequencies, and conformer energies calculated using the density
      functional theory are in good agreement with the previous theoretical
      predictions. At 315 K, the cis-cis conformer has a very short life time and
      transforms easily to the cis-trans conformer through a change in the O=C-O-H
      dihedral angle. The energy difference between the trans-trans and cis-trans
      conformers is very small (approximately 1 kcal/mol), but the trans-trans
      conformer is resistant to dissociation to carbon dioxide and water. The cis-trans
      conformer has a relatively short path for one of its hydroxyl groups to accept
      the proton from the other end of the molecule, resulting in a lower activation
      barrier for dissociation. Comparison of the free and potential energies of
      dissociation shows that the entropic contribution to the dissociation energy is
      less than 10%. The potential energy barrier for dissociation of H2CO3 to CO2 and
      H2O from the metadynamics calculations is 5-6 kcal/mol lower than in previous 0 K
      studies, possibly due to a combination of a finite temperature and more efficient
      sampling of the energy landscape in the metadynamics calculations. Gas phase
      carbonic acid dissociation is triggered by the dehydroxylation of one of the
      hydroxyl groups, which reorients as it approaches the proton on the other end of
      the molecule, thus facilitating a favorable H-O-H angle for the formation of a
      product H2O molecule. The major atomic reorganization of the other part of the
      molecule is a gradual straightening of the O=C=O bond. The metadynamics results
      provide a basis for future simulation of the more challenging carbonic acid-water
      system.

PMID- 17552772
TI  - Intra- and intermolecular vibrational energy transfer in tungsten carbonyl
      complexes W(CO)5(X) (X=CO, CS, CH3CN, and CD3CN).
AB  - Vibrational energy relaxation of degenerate CO stretches of four tungsten
      carbonyl complexes, W(CO)6, W(CO)5(CS), W(CO)5(CH3CN), and W(CO)5(CD3CN), is
      observed in nine alkane solutions by subpicosecond time-resolved infrared (IR)
      pump-probe spectroscopy. Between 0 and 10 ps after the vibrational excitation,
      the bleaching signal of the ground-state IR absorption band shows anisotropy.
      Decay of the anisotropic component corresponds either to the rotational diffusion
      of the molecule or to the intramolecular vibrational energy transfer among the
      degenerate CO stretch modes. The time constant of the anisotropy decay, tauaniso,
      shows distinct solvent dependence. By comparing the results for the T1u CO
      stretch of W(CO)6 and the A1 CO stretch of W(CO)5(CS), the time constant of the
      rotational diffusion, taur, and the time constant of the intramolecular energy
      transfer among the three degenerate vibrational modes, taue, are determined as 12
      and 8 ps, respectively. The tauaniso value increases as the number of carbon
      atoms in the alkane solvent increases. After 10 ps, the recovery of the bleaching
      becomes isotropic. The isotropic decay represents the vibrational population
      relaxation, from v=1 to v=0. In heptane, the time constant for the isotropic
      decay, tau1, for W(CO)5(CS) and W(CO)6 was 140 ps. The tau1 for the two
      acetonitrile-substituted complexes, however, shows a smaller value of 80 ps. The
      vibrational energy relaxation of W(CO)5(CH3CN) and W(CO)5(CD3CN) is accelerated
      by the intramolecular energy redistribution from the CO ligand to the
      acetonitrile ligand. In the nine alkane solutions, the tau1 value of W(CO)6
      ranges between 124 and 158 ps, showing the apparent V-shaped solvent dependence
      with its minimum in decane, while the tau1 value shows little solvent dependence
      for W(CO)5(CH3CN) and W(CO)5(CD3CN).

PMID- 17552773
TI  - Thermodynamic performance of a laser cryocooler.
AB  - The quantum dynamic action of a laser cooling system is analyzed by means of a
      simplified luminescence center model with ground state and excited state in this
      paper. The thermodynamic performance of a laser cryocooler is described by
      solving quantum master equation. The cooling load and the coefficient of
      performance of the cooler are obtained by using finite time thermodynamics. Some
      features of the system under the weak coupling and under the intense coupling
      conditions are discussed.

PMID- 17552774
TI  - Relaxation theory of the electronic spin of a complexed paramagnetic metal ion in
      solution beyond the Redfield limit.
AB  - The relaxation of the electronic spin S of a paramagnetic metal ion with fully
      quenched orbital angular momentum in its ground state is investigated in an
      external magnetic field through a systematic study of the time correlation
      functions governing the evolution of the statistical operator (density matrix).
      Let omega0 be the Larmor angular frequency of S. When the relaxation is induced
      by a time-fluctuating perturbing Hamiltonian hH1(t) of time correlation tauc, it
      is demonstrated that after a transient period the standard Redfield approximation
      is relevant to calculate the evolution of the populations of the spin states if
      parallelH1 parallel2tauc2/(1+omega0(2)tauc2)<<1 and that this transient period
      becomes shorter than tauc at sufficiently high field for a zero-field splitting
      perturbing Hamiltonian. This property, proven analytically and confirmed by
      numerical simulation, explains the surprising success of several simple
      expressions of the longitudinal electronic relaxation rate 1/T1e derived from the
      Redfield approximation well beyond its expected validity range parallelH1
      paralleltauc<<1. It has favorable practical consequences on the interpretation of
      the paramagnetic relaxation enhancement of nuclei used for structural and dynamic
      studies.

PMID- 17552775
TI  - Low-field approach to double resonance in nuclear quadrupole resonance of spin-1
      nuclei.
AB  - Using double-resonance conditions, in which the Larmor frequency of a spin-1/2
      nucleus is matched to one of the nuclear quadrupole resonance frequencies of a
      spin-1 nucleus, the authors demonstrate increased cross relaxation between the
      two nuclear spin species. They calculate the cross-relaxation rate using the
      motionally averaged heterogeneous dipole Hamiltonian as a perturbation to the
      combined quadrupole and Zeeman Hamiltonians. Using this cross-relaxation rate, in
      addition to hydrogen and nitrogen autorelaxation rates, expressions governing
      spin-1/2 and spin-1 spin-lattice relaxation are determined. With ammonium
      nitrate, containing nitrogen (spin-1) and hydrogen (spin-1/2), increased nitrogen
      signal and spin-lattice relaxation are demonstrated, using fields less than 120
      G. The cross-relaxation rate is also measured and an overall signal/noise
      improvement by a factor of 2.3+/-0.1 is attained.

PMID- 17552776
TI  - Phase-ordering kinetics of the liquid-liquid transition in single-component
      molecular liquids.
AB  - Recently it has been revealed that even a single-component liquid can have more
      than two liquid states. The transition between these liquid states is called the
      "liquid-liquid transition." Most known liquid-liquid transitions occur at
      temperatures and pressures which are difficult to access experimentally, so the
      physical nature of the transition, particularly the kinetics, has remained
      elusive. However, the recent discovery of liquid-liquid transitions in molecular
      liquids opens up a possibility to study the kinetics in detail. Here, we report
      the first phase field simulation on the kinetics of a liquid-liquid transition
      and its direct comparison with experimental results of the molecular liquids.
      Both nucleation-growth-type and spinodal-decomposition-type liquid-liquid
      transformation observed experimentally are well reproduced by numerical
      simulation based on a two-order-parameter model of liquid that regards the liquid
      liquid transition as the cooperative formation of locally favored structures.
      Thus, phase field calculations may allow us to predict the kinetics of liquid
      liquid transitions and the resulting spatiotemporal change of various physical
      properties of the liquid, such as density and refractive index.

PMID- 17552777
TI  - Free energy calculation of water addition coupled to reduction of aqueous RuO4-.
AB  - Free energy calculations were carried out for water addition coupled reduction of
      aqueous ruthenate, RuO4-+H2O+e--->[RuO3(OH)2]2-, using Car-Parrinello molecular
      dynamics simulations. The full reaction is divided into the reduction of the
      tetrahedral monoanion, RuO4-+e--->RuO4(2-), followed by water addition, RuO4(2
      )+H2O-->[RuO3(OH)2]2-. The free energy of reduction is computed from the
      fluctuations of the vertical energy gap using the MnO4-+e--->MnO(4)2- reaction as
      reference. The free energy for water addition is estimated using constrained
      molecular dynamics methods. While the description of this complex reaction, in
      principle, involves multiple reaction coordinates, we found that reversible
      transformation of the reactant into the product can be achieved by control of a
      single reaction coordinate consisting of a suitable linear combination of atomic
      distances. The free energy difference of the full reaction is computed to be 
      0.62 eV relative to the normal hydrogen electrode. This is in good agreement with
      the experimental value of -0.59 eV, lending further support to the hypothesis
      that, contrary to the ruthenate monoanion, the dianion is not tetrahedral but
      forms a trigonal-bipyramidal dihydroxo complex in aqueous solution. We construct
      an approximate two-dimensional free energy surface using the coupling parameter
      for reduction and the mechanical constraint for water addition as variables.
      Analyzing this surface we find that in the most favorable reaction pathway the
      reduction reaction precedes water addition. The latter takes place via the
      protonated complex [RuO3(OH)]- and subsequent transport of the created hydroxide
      ion to the fifth coordination site of Ru.

PMID- 17552778
TI  - Efficient trapping of silver cations in a rare gas matrix: Ag3+ in argon.
AB  - Mass selected cations of Ag clusters are deposited, together with Ar seeded with
      CO2 (or other electron scavengers such as O2, N2O, or CCl4), on a cold substrate,
      while being flooded with low energy electrons. Optical absorption measurements
      reveal an efficient trapping of Ag cluster cations in the Ar matrix, provided
      that CO2 or another electron scavenger is present to ensure charge neutrality of
      the matrix. The spectrum of Ag3+ thus obtained is in excellent agreement with
      previous predictions from quantum chemical calculations.

PMID- 17552779
TI  - Lindemann measures for the solid-liquid phase transition.
AB  - A set of Lindemann measures, based on positional deviations or return distances,
      defined with respect to mechanically stable inherent structure configurations, is
      applied to understand the solid-liquid phase transition in a Lennard-Jones-type
      system. The key quantity is shown to be the single-particle return distance
      squared distribution. The first moment of this distribution is related to the
      Lindemann parameter which is widely used to predict the melting temperature of a
      variety of solids. The correlation of the single-particle return distance and
      local bond orientational order parameter in the liquid phase provides insights
      into mechanisms for melting. These generalized Lindemann measures, especially the
      lower order moments of the single-particle return distance distribution, show
      clear signatures of the transition of the liquid from the stable to the
      metastable, supercooled regime and serve as landscape-based indicators of the
      thermodynamic freezing transition for the Lennard-Jones-type system investigated.

PMID- 17552780
TI  - Solvent effects on two-photon absorption of dialkylamino substituted
      distyrylbenzene chromophore.
AB  - Solvent effects on the two-photon absorption of a symmetrical diamino substituted
      distyrylbenzene chromophore have been studied using the density functional
      response theory in combination with the polarizable continuum model. It is shown
      that the dielectric medium has a rather small effect both on the bond length
      alternation and on the one-photon absorption spectrum, but it affects
      significantly the two-photon absorption cross section. It is found that both one-
      and two-photon absorptions are extremely sensitive to the planarity of the
      molecule, and the absorption intensity can be dramatically reduced by the
      conformation distortion. It has led to the conclusion that the experimentally
      observed anomalous solvent effect on the two-photon absorption of dialkylamino
      substituted distyrylbenzene chromophores cannot be attributed to the intrinsic
      properties of a single molecule and its interaction with solvents.

PMID- 17552781
TI  - Thermally activated delayed fluorescence as a cycling process between excited
      singlet and triplet states: application to the fullerenes.
AB  - In efficient thermally activated delayed fluorescence (TADF) the excited
      chromophore alternates randomly between the singlet and triplet manifolds a large
      number of times before emission occurs. In this work, the average number of
      cycles n is obtained and is shown to have a simple experimental meaning: n+1 is
      the intensification factor of the prompt fluorescence intensity, owing to the
      occurrence of TADF. A new method of data analysis for the determination of the
      quantum yield of triplet formation, combining steady-state and time-resolved data
      in a single plot, is also presented. Application of the theoretical results to
      the TADF of [70]fullerenes shows a general good agreement between different
      methods of fluorescence analysis and allows the determination of several
      photophysical parameters.

PMID- 17552782
TI  - Equilibrium and nonequilibrium molecular dynamics simulations of the thermal
      conductivity of molten alkali halides.
AB  - The thermal conductivity of molten NaCl and KCl was calculated through the Evans
      Gillan nonequilibrium molecular dynamics (NEMD) algorithm and Green-Kubo
      equilibrium molecular dynamics (EMD) simulations. The EMD simulations were
      performed for a "binary" ionic mixture and the NEMD simulations assumed a pure
      system for reasons discussed in this work. The cross thermoelectric coefficient
      obtained from Green-Kubo EMD simulations is discussed in terms of the homogeneous
      thermoelectric power or Seebeck coefficient of these materials. The thermal
      conductivity obtained from NEMD simulations is found to be in very good agreement
      with that obtained through Green-Kubo EMD simulations for a binary ionic mixture.
      This result points to a possible cancellation between the neglected "partial
      enthalpy" contribution to the heat flux associated with the interdiffusion of one
      species through the other and that part of the thermal conductivity related to
      the coupled fluxes of charge and heat in "binary" ionic mixtures.

PMID- 17552783
TI  - Electron stimulated reactions of methyl iodide coadsorbed with amorphous solid
      water.
AB  - The electron stimulated reactions of methyl iodide (MeI) adsorbed on and
      suspended within amorphous solid water (ice) were studied using a combination of
      postirradiation temperature programmed desorption and reflection absorption
      infrared spectroscopy. For MeI adsorbed on top of amorphous solid water (ice),
      electron beam irradiation is responsible for both structural and chemical
      transformations within the overlayer. Electron stimulated reactions of MeI result
      principally in the formation of methyl radicals and solvated iodide anions. The
      cross section for electron stimulated decomposition of MeI is comparable to the
      gas phase value and is only weakly dependent upon the local environment. For both
      adsorbed MeI and suspended MeI, reactions of methyl radicals within MeI clusters
      lead to the formation of ethane, ethyl iodide, and diiodomethane. In contrast,
      reactions between the products of methyl iodide and water dissociation are
      responsible for the formation of methanol and carbon dioxide. Methane, formed as
      a result of reactions between methyl radicals and either parent MeI molecules or
      hydrogen atoms, is also observed. The product distribution is found to depend on
      the film's initial chemical composition as well as the electron fluence. Results
      from this study highlight the similarities in the carbon-containing products
      formed when monohalomethanes coadsorbed with amorphous solid water are irradiated
      by either electrons or photons.

PMID- 17552784
TI  - Light trapping and guidance in plasmonic nanocrystals.
AB  - We illustrate the possibility of light trapping and funneling in periodic arrays
      of metallic nanoparticles. A controllable minimum in the transmission spectra of
      such constructs arises from a collective plasmon resonance phenomenon, where an
      incident plane wave sharply localizes in the vertical direction, remaining
      delocalized in the direction parallel to the crystal plane. Using hybrid arrays
      of different structures or different materials, we apply the trapping effect to
      structure the eigenmode spectrum, introduce overlapping resonances, and hence
      direct the light in space in a wavelength-sensitive fashion.

PMID- 17552785
TI  - Two-dimensional infrared surface spectroscopy for CO on Cu(100): detection of
      intermolecular coupling of adsorbates.
AB  - Surface-specific infrared signals obtained by subjecting the system to two
      infrared laser pulses are calculated for an admixture of CO and isotopic CO on
      Cu(100) by using molecular dynamics simulation based on a stability matrix
      formalism. The two-dimensional profiles of the signals in the frequency domain
      show both diagonal and cross peaks. The former peaks mainly arise from the
      overtones of the CO and isotopic CO, while the latter represent the couplings
      between those. As temperature is increased, the phases of cross peaks in a second
      order infrared response function change significantly, while those of diagonal
      peaks are unchanged. The authors show that the phase shifts are originated from
      the potential anharmonicities due to the electronic interaction between
      adsorbates. Using a model with two dipole moments, they find that the frustrated
      rotational mode activated with temperature has effects on the anharmonicity.
      These results indicate that two-dimensional infrared surface spectroscopy reveals
      the anharmonic couplings between adsorbates and surface atoms or between
      adsorbates which cannot be observed in first-order spectroscopy.

PMID- 17552786
TI  - Comparison of critical adsorption scaling functions obtained from neutron
      reflectometry and ellipsometry.
AB  - Carpenter et al. [Phys. Rev. E 59, 5655 (1999); 61, 532 (2000)] managed to
      explain ellipsometric critical adsorption data collected from the liquid-vapor
      interface of four different critical binary liquid mixtures near their demixing
      critical temperature using a single model. This was the first time a single
      universal function had been found which could quantitatively describe the surface
      critical behavior of many different mixtures. There have also been various
      attempts to investigate this surface critical behavior using neutron and x-ray
      reflectometries. Results have been mixed and have often been at variance with
      Carpenter et al. In this paper, the authors show that neutron reflectometry data
      collected from a crystalline quartz-critical mixture interface, specifically
      deuterated water plus 3-methylpyridine, can be quantitatively explained using the
      model of Carpenter et al. derived from ellipsometric data.

PMID- 17552787
TI  - Disruption of hydrogen bond structure of water near charged electrode surfaces.
AB  - The understanding of the hydrogen (H) bonded structure of water near charged
      surfaces is highly relevant in the context of several important areas of
      research, including electrochemistry, biochemistry, and geology. Past simulation
      studies have not yielded conclusive answers; while some suggest breakage of H
      bonds near a charged surface, others argue that H-bonding interactions can
      stabilize the structure of surface water even in the presence of high electric
      (E) fields. Recent experiments, on the other hand, suggest a partial breakdown of
      H-bond structure near a charged electrode. In all these studies, however, the
      conclusions regarding H bonding were drawn based on the density profile of
      hydrogen/oxygen atoms near the interface. In the present paper, we investigate
      this problem using a new theory that explicitly accounts for the influence of E
      field on the H-bond network of water near the solid-liquid interface. We find
      that the average number of H bonds per molecule in bulk increases from
      approximately 3.8 at E<10(5) V/m to approximately 3.95 at E=2x10(9) V/m
      (suggesting enhancement in H-bond network), while that near the electrode surface
      decreases from approximately 2.8 to a saturation value of approximately 2.0
      (suggesting weakening of H-bond network).

PMID- 17552788
TI  - Phase shift induces currents in a periodic tube.
AB  - The average current of an overdamped Brownian particle moving along the axis of a
      three-dimensional periodic tube is investigated in the presence of a symmetric
      potential and a temporally symmetric unbiased external force. Reduction of the
      spatial dimensionality from two or three physical dimensions to an effective one
      dimensional system entails the appearance of not only an entropic barrier but
      also an effective diffusion coefficient. The authors find that the phase shift
      between the tube shape and the potential can break the symmetry of the effective
      potential and can induce net currents. Under optimal condition, the current as a
      function of temperature and the phase shift possesses many extrema of alternating
      signs. The current may reverse its direction several times when temperature or
      the phase shift is changed. The authors' model is to describe the movement of
      molecular motors along microtubule.

PMID- 17552789
TI  - Temperature, composition, and hydrogen isotope effect in the hydrogenation of CO
      on amorphous ice surface at 10-20 K.
AB  - An experiment on the addition reaction of a D atom (deuteration) to CO on a cold
      ice surface is performed by deuterium atom exposure of three types of samples
      (pure solid CO, CO-capped H2O ice, and CO-H2O mixed ice) at 10-20 K. The
      variation of IR absorption spectra for the samples was measured by a Fourier
      transform infrared spectrometer during exposure to deuterium atoms. Reactions on
      pure solid CO were observed only at 10 K, while reactions on CO-capped H2O ice
      and CO-H2O mixed ice were observed to proceed even at 20 K. This indicates that
      the coexistence of H2O at the surface raises the reactive temperature. In
      addition, the experiment on H atom exposure was also carried out at 15 K to
      compare the reaction rate constant between the H and D atoms. The ratio of
      reaction rate constant kD/kH obtained is about 0.08 at 15 K. The authors provide
      information on the potential energy for the H+CO reaction at the surface by using
      the ratio kD/kH and by a model calculation of the potential tunneling with the
      asymmetric Eckart potential.

PMID- 17552790
TI  - Ultrafast photoinduced electron transfer from dimethylaniline to coumarin dyes in
      sodium dodecyl sulfate and triton X-100 micelles.
AB  - The primary steps of photoinduced electron transfer (PET) from N,N
      dimethylaniline (DMA) to five coumarin dyes are studied in an anionic micelle
      [sodium dodecyl sulfate (SDS)] and a neutral micelle [triton X-100 (TX-100)]
      using femtosecond upconversion. The rate of PET in micelle is found to be highly
      nonexponential. In both the micelles, PET displays components much faster
      (approximately 10 ps) than the slow components (180-2900 ps) of solvation
      dynamics. The ultrafast components of electron transfer exhibit a bell-shaped
      dependence on the free energy change. This is similar to Marcus inversion. The
      rates of PET in TX-100 and SDS micelle are, in general, faster than those in
      cetyltrimethylammonium bromide (CTAB) micelle. In the SDS and TX-100 micelle, the
      Marcus inversion occurs at -DeltaG0 approximately 0.7 eV which is lower than that
      (approximately 1.2 eV) in CTAB micelle. Possible causes of variation of PET in
      different micelles are discussed.

PMID- 17552791
TI  - Amorphous and crystalline phases in thermal quench simulations of alumina.
AB  - The authors report molecular dynamics simulations of alumina (Al2O3) during
      crystallization from the melt. Using liquid quench methods, they investigate the
      effect of cooling rate on the structural evolution of the alpha, kappa, and the
      bixbyite phases. A critical temperature window is identified, where the time
      spent in this window is crucial in determining the extent to which the systems
      approach crystallinity. A strong dependence is observed between the final
      structure and the quench rate, which is most pronounced for the alpha phase and
      to lesser extent for the other phases. The results show that the different phases
      have different tendencies to crystallize that are determined by energetics,
      complexity of crystal structure, and the number of metastable states.

PMID- 17552792
TI  - How strongly can calcium ion influence the hydrogen-bond dynamics at complex
      aqueous interfaces?
AB  - The author has performed three independent molecular dynamics computer
      simulations to examine the effects of counterion identity on hydrogen-bond
      dynamics in the enclosed water pool of anionic surfactant-based reverse micelles.
      The water-water hydrogen-bond lifetime in the reverse micelle (RM) with calcium
      ions is found to be longer than that in the RM with sodium or ammonium ions. The
      hydrogen bond between a polar head group and a water molecule, on the other hand,
      breaks but reforms most rapidly in the RM with calcium ions, indicating that
      there exists a strong competition between head group-counterion and head group
      water interactions at such complex interfaces.

PMID- 17552793
TI  - Does phenomenological kinetics provide an adequate description of heterogeneous
      catalytic reactions?
AB  - Phenomenological kinetics (PK) is widely used in the study of the reaction rates
      in heterogeneous catalysis, and it is an important aid in reactor design. PK
      makes simplifying assumptions: It neglects the role of fluctuations, assumes that
      there is no correlation between the locations of the reactants on the surface,
      and considers the reacting mixture to be an ideal solution. In this article we
      test to what extent these assumptions damage the theory. In practice the PK rate
      equations are used by adjusting the rate constants to fit the results of the
      experiments. However, there are numerous examples where a mechanism fitted the
      data and was shown later to be erroneous or where two mutually exclusive
      mechanisms fitted well the same set of data. Because of this, we compare the PK
      equations to "computer experiments" that use kinetic Monte Carlo (kMC)
      simulations. Unlike in real experiments, in kMC the structure of the surface, the
      reaction mechanism, and the rate constants are known. Therefore, any discrepancy
      between PK and kMC must be attributed to an intrinsic failure of PK. We find that
      the results obtained by solving the PK equations and those obtained from kMC,
      while using the same rate constants and the same reactions, do not agree.
      Moreover, when we vary the rate constants in the PK model to fit the turnover
      frequencies produced by kMC, we find that the fit is not adequate and that the
      rate constants that give the best fit are very different from the rate constants
      used in kMC. The discrepancy between PK and kMC for the model of CO oxidation
      used here is surprising since the kMC model contains no lateral interactions that
      would make the coverage of the reactants spatially inhomogeneous. Nevertheless,
      such inhomogeneities are created by the interplay between the rate of adsorption,
      of desorption, and of vacancy creation by the chemical reactions.

PMID- 17552794
TI  - Unforced translocation of a polymer chain through a nanopore: the solvent effect.
AB  - The authors have performed the Langevin dynamics simulation to investigate the
      unforced polymer translocation through a narrow nanopore in an impermeable
      membrane. The effects of solvent quality controlled by the attraction strength
      lambda of the Lennard-Jones cosine potential between polymer beads and beads on
      two sides of the membrane on the translocation processes are extensively
      examined. For polymer translocation under the same solvent quality on both sides
      of the membrane, the two-dimensional and three-dimensional simulations confirm
      the scaling law of tautrans approximately N1+2upsilon for the translocation in
      the good solvent, where tautrans is the translocation time, N is the chain
      length, and upsilon is the Flory exponent. For the three-dimensional polymer
      translocation under different solvent qualities on two sides of the membrane, the
      translocation efficiency may be notably improved. The scaling law between
      tautrans and N varies from tautrans approximately N1+2upsilon to tautrans
      approximately N with the increase of the difference of solvent qualities, and the
      crossover occurs at the theta temperature point, where a scaling law of tautrans
      approximately N1.27 is found. The simulation results here also show that the
      translocation time changes from a wide and asymmetric distribution with a long
      tail to a narrow and symmetric distribution with the increase of the difference
      of the solvent qualities.

PMID- 17552795
TI  - Nonexponential polymer segmental motion in the presence and absence of ions: 2H
      NMR multitime correlation functions for polymer electrolytes poly(propylene
      glycol)-LiClO4.
AB  - The authors measure 2H NMR multitime correlation functions to investigate the
      segmental motion of poly(propylene glycol) containing various amounts of the salt
      LiClO4. 2H NMR two-time correlation functions indicate that addition of salt
      affects not only the time scale of the segmental motion, but also the degree of
      the nonexponential relaxation behavior. To quantify the origin of the
      nonexponential segmental motion, the authors analyze 2H NMR three-time
      correlation functions. In general, nonexponential relaxation can result from
      homogeneous dynamics, i.e., intrinsic nonexponentiality, and from heterogeneous
      dynamics, i.e., existence of a distribution of correlation times G(ln tau). For
      the studied high and low salt concentrations, including neat poly(propylene
      glycol), the analysis shows that both homogeneous and heterogeneous contributions
      are important. 2H NMR four-time correlation functions allow the authors to
      measure the lifetime of the dynamical heterogeneities. For the studied salt
      concentrations, the rate exchange occurs on the same time scale as the segmental
      motion, indicating short-lived dynamical heterogeneities. To arrive at these
      results, the authors reconsider the interpretation of (2)H NMR three-time
      correlation functions. Results of analytical calculations and computer
      simulations show that it is necessary to extend the previous way of analysis so
      as to include effects due to correlated back-and-forth jumps.

PMID- 17552796
TI  - Self-assembled morphologies of diblock copolymers confined in nanochannels:
      effects of confinement geometry.
AB  - The self-assembly of diblock copolymers confined in channels of various shaped
      cross sections is studied using a simulated annealing technique with the "single
      site bond fluctuation" model. In the bulk, the asymmetric diblock copolymers used
      in this study form hexagonally packed cylinders with period L0. The cross
      sections of the confining channels are of different shapes including regular
      triangles, rectangles, squares, regular hexagons, regular octagons, and ellipses.
      For a given geometry, the channel size (characterized by one or two lengths) is
      varied from very small to several times of L0. It is found that the geometry and
      size of the confining channels have a large effect on the structure and symmetry
      of the self-assembled morphologies. Multiple packed cylinders with the symmetry
      of the confining channels are the major morphologies for low-symmetry cross
      sections such as triangle, rectangle, and square. More complex structures such as
      helices or stacked toroids spontaneously form when the confining channels are
      shaped such as a regular hexagon, a regular octagon, or an ellipse. The domain
      spacing of the self-assembled structures can be altered by the shape and size of
      the confining channels. Our results are consistent with available experiments.
      These results indicate that the self-assembled structures of block copolymers can
      be manipulated by the shape of the confining channels.

PMID- 17552797
TI  - "Self-concentration" effects on the dynamics of a polychlorinated biphenyl
      diluted in 1,4-polybutadiene.
AB  - The mobility of isolated polychlorinated biphenyl (PCB54) in 1,4-polybutadiene
      (PB) has been investigated by means of broadband dielectric spectroscopy. The aim
      was to provide new insights about the effect of the environment on the dynamics
      of PCB54. The authors' results indicate that PCB54 structural dynamics is neither
      independent of the PB matrix nor slaved to the matrix itself. The authors
      interpret these results as a consequence of the limited size of cooperatively
      rearranging regions (CRRs) involved in PCB54 structural relaxation possessing an
      effective concentration different from the macroscopic one. This implies a non
      negligible influence of "self-concentration," already proven for the component
      segmental dynamics in polymer blends, also in the relaxation of binary mixtures
      involving low molecular weight glass formers. This allowed the evaluation of the
      size of CRR, which was about 1 nm for PCB54 in PB. This means that the
      cooperativity extends over the first shell around PCB54 molecules.

PMID- 17552798
TI  - Influence of an electric field on the non-Newtonian response of a hybrid-aligned
      nematic cell under shear flow.
AB  - The authors study shear flow in hybrid-aligned nematic cells under the action of
      an applied electric field by solving numerically a hydrodynamic model. The
      authors apply this model to a flow-aligning nematic liquid crystal (4'-n-pentyl-4
      cyanobiphenyl) and obtain the director's configuration and the velocity profile
      at the stationary state. The authors calculate the local and apparent viscosities
      of the system and found that the competition between the shear flow and the
      electric field gives rise to an interesting non-Newtonian response with regions
      of shear thickening and thinning. The results also show an important
      electrorheological effect ranging from a value a bit larger than the Miesowicz
      viscosity etab [Nature (London) 17, 261 (1935)] for small electric fields and
      large shear flows to etac for large electric fields and small shear flows. The
      analysis of the first normal stress difference shows that for small negative
      shear rates, the force between the plates of the cell is attractive, while it is
      repulsive for all other values of shear rates. However, under the application of
      the electric field, one can modify the extent of the region of attraction.
      Finally, the authors have calculated the dragging forces on the plates of the
      cell and found that it is easier to shear in one direction than in the other.

PMID- 17552799
TI  - Comparative study of temperature dependent orientational relaxation in a model
      thermotropic liquid crystal and in a model supercooled liquid.
AB  - Recent optical Kerr effect experiments have revealed a power law decay of the
      measured signal with a temperature independent exponent at short-to-intermediate
      times for a number of liquid crystals in the isotropic phase near the isotropic
      nematic transition and supercooled molecular liquids above the mode coupling
      theory critical temperature. In this work, the authors investigate the
      temperature dependence of short-to-intermediate time orientational relaxation in
      a model thermotropic liquid crystal across the isotropic-nematic transition and
      in a binary mixture across the supercooled liquid regime in molecular dynamics
      simulations. The measure of the experimentally observable optical Kerr effect
      signal is found to follow a power law decay at short-to-intermediate times for
      both systems in agreement with recent experiments. In addition, the temperature
      dependence of the power law exponent is found to be rather weak. As the model
      liquid crystalline system settles into the nematic phase upon cooling, the decay
      of the single-particle second-rank orientational time correlation function
      exhibits a pattern that is similar to what has been observed for supercooled
      liquids.

PMID- 17552800
TI  - Dynamics of polymer melts confined by smooth walls: crossover from nonentangled
      region to entangled region.
AB  - The authors present the results of molecular dynamics simulations of polymer
      films confined by smooth walls. Simulations were performed for a wide range of
      chain lengths covering both nonentangled and entangled regions, as well as film
      thicknesses ranging from the order of unperturbed chain size to the bulk state.
      The simulation results for the chain size dependence on the film thickness are
      compared with the prediction of the scaling model. By measuring the correlation
      function of the end-to-end vectors, we have determined the relaxation time of
      confined polymer chains in different entangled states. It is shown that there is
      a minimum in the relaxation time of long chains when decreasing the film
      thickness, which is partially due to the confinement-induced disentanglement
      effect.

PMID- 17552801
TI  - Car-Parrinello simulation of an O-H stretching envelope and potential of mean
      force of an intramolecular hydrogen bonded system: application to a Mannich base
      in solid state and in vacuum.
AB  - Car-Parrinello molecular dynamics (CPMD) study was performed for an anharmonic
      system-an intramolecularly hydrogen bonded Mannich-base-type compound, 4,5
      dimethyl-2(N,N-dimethylaminemethyl)phenol, to investigate the vibrational
      spectrum associated with the O-H stretching. Calculations were carried out for
      the solid state and for an isolated molecule. The classical CPMD simulation was
      performed and then the proton potential snapshots were extracted from the
      trajectory. The vibrational Schrodinger equation for the snapshots was solved
      numerically, and the (O-H) envelope was calculated as a superposition of the 0-
      >1 transitions. The potential of mean force for the proton stretching mode was
      calculated from the proton vibrational eigenfunctions and eigenvalues
      incorporating statistical sampling, nuclear quantum effects, and effects of the
      environment. Perspectives for application of the presented methodology in the
      computational support of biocatalysis are given in the study.

PMID- 17552804
TI  - Perspective: photoacoustic spectroscopy: "Linearization and signal recovery in
      photoacoustic infrared spectroscopy" [Rev. Sci. Instrum. 78, 051301 (2007)].

PMID- 17552805
TI  - Invited article: Linearization and signal recovery in photoacoustic infrared
      spectroscopy.
AB  - Photoacoustic (PA) infrared spectroscopy enables the characterization of a wide
      variety of materials, affording the spectroscopist several advantages over more
      traditional infrared methods. While PA spectra are readily acquired using
      commercial instrumentation, the quality of the data can be improved substantially
      through the use of specialized numerical and experimental procedures. Two of
      these methods are the subject of this review. Specifically, this article
      describes (a) linearization of PA infrared spectra, a calculation that
      incorporates phase and amplitude information to extend the range of linearity for
      strongly absorbing samples, and (b) lock-in and digital signal-recovery
      procedures in step-scan phase-modulation PA infrared spectroscopy. Linearization
      yields significant improvement in band definition, especially in the low
      wavenumber region. This numerical method succeeds in situations where the PA
      phase of the sample is less than that of the reference (carbon black). When this
      criterion is not met initially, the sample or reference interferograms can be
      manipulated prior to the calculation. The steps involved in linearization are
      illustrated in detail and approximations are discussed. Lock-in demodulation of
      the step-scan phase-modulation signal is compared to digital (software)
      demodulation in this study; the lock-in technique is found to be superior in
      several cases. The imaginary interferograms in these experiments sometimes lack a
      strong central feature, a situation that necessitates the application of less
      commonly used methods for phase correction and spectrum calculation. These
      methods, which are available in commercial software, include two-quadrant and
      stored-phase corrections. The PA phase spectrum resembles amplitude and
      absorption spectra when real and imaginary PA spectra are correctly calculated.

PMID- 17552806
TI  - Design and performance of a curved-crystal x-ray emission spectrometer.
AB  - A curved-crystal x-ray emission spectrometer has been designed and built to
      measure 2-5 keV x-ray fluorescence resulting from a core-level excitation of gas
      phase species. The spectrometer can rotate 180 degrees, allowing detection of
      emitted x rays with variable polarization angles, and is capable of collecting
      spectra over a wide energy range (20 eV wide with 0.5 eV resolution at the Cl K
      edge) simultaneously. In addition, the entire experimental chamber can be rotated
      about the incident-radiation axis by nearly 360 degrees while maintaining vacuum,
      permitting measurements of angular distributions of emitted x rays.

PMID- 17552807
TI  - Low-noise rotating sample holder for ultrafast transient spectroscopy at
      cryogenic temperatures.
AB  - We present the design and testing of a rotating device that fits within a
      commercial helium cryostat and is capable of providing at 4 K a fresh sample
      surface for subsequent shots of a 1-10 kHz amplified pulsed laser. We benchmark
      this rotator in a transient-absorption experiment on molecular switches. After
      showing that the device introduces only a small amount of additional noise, we
      demonstrate how the effect of signal degradation due to high fluence is
      completely resolved.

PMID- 17552808
TI  - Fully automated time domain spectrometer for the absorption and scattering
      characterization of diffusive media.
AB  - We describe a system for absorption and scattering spectroscopy of diffusive
      media based on time-resolved reflectance and transmittance measurements. The
      system is operated with mode-locked lasers tunable in the 550-1050 nm spectral
      range and on a detection chain based on time-correlated single-photon counting.
      All measurement procedures such as laser tuning and optimization, signal
      conditioning, data acquisition, and analysis are completely automated, permitting
      spectral measurements over the whole range in a few minutes. The criticalities of
      the system are discussed together with the strategies to compensate them. The
      Medphot protocol devised for the characterization of photon migration instruments
      was applied to assess the system performances in terms of accuracy, linearity,
      noise, stability, and reproducibility. Finally, an example of application of the
      instrument to the spectroscopy of powders is presented.

PMID- 17552809
TI  - Closed-loop wavelength stabilization of an optical parametric oscillator as a
      front end of a high-power iodine laser chain.
AB  - We present a complex stabilization and control system for a commercially
      available optical parametric oscillator. The system is able to stabilize the
      oscillator's output wavelength at a narrow spectral line of atomic iodine with
      subpicometer precision, allowing utilization of this solid-state parametric
      oscillator as a front end of a high-power photodissociation laser chain formed by
      iodine gas amplifiers. In such setup, a precise wavelength matching between the
      front end and the amplifier chain is necessary due to extremely narrow spectral
      lines of the gaseous iodine (approximately 20 pm). The system is based on a
      personal computer, a heated iodine cell, and a few other low-cost components. It
      automatically identifies the proper peak within the iodine absorption spectrum,
      and then keeps the oscillator tuned to this peak with high precision and
      reliability. The use of the solid-state oscillator as the front end allows us to
      use the whole iodine laser system as a pump laser for the optical parametric
      chirped pulse amplification, as it enables precise time synchronization with a
      signal Ti:sapphire laser.

PMID- 17552810
TI  - Experimental technique using FTIR to estimate IR optical properties at variable
      temperatures: application to PMDA-ODA polyimide thin films from 100 to 380
      degrees C.
AB  - An experimental technique is presented to measure reflectance at high sample
      temperature with respect to room temperature in the infrared using Fourier
      transform infrared fitted with a reflectometer. Sample temperature artifacts are
      accounted for by sequential measurements taken with the lamp source on and with
      the lamp source off. The sequential measurements are shown mathematically to
      correct for the modulation of sample and detector thermal emissions. Further, the
      technique is applied to a polyimide (PMDA-ODA) film on a layer of gold deposited
      on a thermally oxidized Si wafer. It is shown that the optical properties (index
      of refraction and extinction coefficient) remain relatively constant with
      temperature (from room temperature to 380 degrees C) in the 4000-6000 cm(-1)
      spectral region. The significant changes that occur with temperature are the
      change in thickness of the film and also the spectral properties in the 2000-4000
      cm(-1) region. Also, by using a Lorentz oscillator model, it is shown that this
      method is able to discern that spectral features corresponding to the OH
      stretching bands at 3630 and 3470 cm(-1) show significant variation with
      increasing temperature.

PMID- 17552811
TI  - All fiber based multispeckle modality endoscopic system for imaging medical
      cavities.
AB  - Disease detection in body cavities, such as the detection of abnormal growths in
      the colon path, has been illustrated here using an image fiber guided catheter
      based multispeckle modality endoscopic system. An all fiber-optic approach for
      the illumination and imaging of the inner cavity walls is adopted here. An
      endoscope probe to carry the illumination fibers as well as the imaging lens
      image fiber unit is designed and custom fabricated in order to operate the probe
      in its various direction sensitive configurations. This is facilitated by the
      selection of suitable optical elements such as beam combiner and biprism at the
      probe proximal end. Experimental investigations were carried out using the
      endoscope system employing phantom model of colon as the test specimen that has
      normal and abnormal (representing growth) regions and the obtained results
      indicated the system effectiveness in identifying the abnormal growths at an
      early stage.

PMID- 17552812
TI  - Characterization of plasma parameters, first beam results, and status of electron
      cyclotron resonance source.
AB  - Electron cyclotron resonance (ECR) plasma source at 50 keV, 30 mA proton current
      has been designed, fabricated, and assembled. Its plasma study has been done.
      Plasma chamber was excited with 350 W of microwave power at 2450 MHz, along with
      nitrogen and hydrogen gases. Microwave power was fed to the plasma chamber
      through waveguide. Plasma density and electron temperature were studied under
      various operating conditions, such as magnetic field, gas pressure, and
      transversal distance. Langmuir probe was used for plasma characterization using
      current-voltage variation. The nitrogen plasma density calculated was
      approximately 4.5 x 10(11) cm(-3), and electron temperatures of 3-10 eV (cold)
      and 45-85 eV (hot) were obtained. The total ion beam current of 2.5 mA was
      extracted, with two-electrode extraction geometry, at 15 keV beam energy. The
      optimization of the source is under progress to extract 30 mA proton beam current
      at 50 keV beam energy, using three-electrode extraction geometry. This source
      will be used as an injector to continuous wave radio frequency quadrupole, a part
      of 100 MeV proton linac. The required root-mean-square normalized beam emittance
      is less than 0.2pi mm mrad. This article presents the study of plasma parameters,
      first beam results, and status of ECR proton source.

PMID- 17552813
TI  - 36-segmented high magnetic field hexapole magnets for electron cyclotron
      resonance ion source.
AB  - Two high magnetic field hexapoles for electron cyclotron resonance ion source
      (ECRIS) have successfully fabricated to provide sufficient radial magnetic
      confinement to the ECR plasma. The highest magnetic field at the inner pole tip
      of one of the magnets exceeds 1.5 T, with the inner diameter (i.d.)=74 mm. The
      other hexapole magnet provides more than 1.35 T magnetic field at the inner pole
      tip, and the i.d. is 84 mm. In this article, we discuss the necessity to have a
      good radial magnetic field confinement and the importance of a Halbach hexapole
      to a high performance ECRIS. The way to design a high magnetic field Halbach
      structure hexapole and one possible solution to the self-demagnetization problem
      are both discussed. Based on the above discussions, two high magnetic field
      hexapoles have been fabricated to be utilized on two high performance ECRISs in
      Lanzhou. The preliminary results obtained from the two ECR ion sources are given.

PMID- 17552814
TI  - Characterization of a heat flux sensor using short pulse laser calibration.
AB  - A method to calibrate classical heat flux sensors is presented. The classical
      approach to measure the temperature inside a known material by using a
      thermocouple fails when the measurement time is very short. In this work the
      surface heat flux is determined by solving the inverse heat conduction problem
      using a noninteger identified system as a direct model for the estimation
      process. Using short pulse laser calibration measurements the crucial design
      aspects of the sensor that play a significant role when assuming one-dimensional,
      semi-infinite heat transfer have been accounted for. The theoretical approach as
      well as the calibration results are presented and comparisons to the classical
      approach and results from finite element modeling are shown. It is concluded that
      the new method ameliorate the heat flux sensor significantly and extend its
      application to very short measurement times.

PMID- 17552815
TI  - Magnetically driven filament probe.
AB  - A radially movable probe has been developed for studies of filamentary transport
      in ASDEX Upgrade during edge localized modes (ELMs) by means of Langmuir tips and
      magnetic pickup coils. The probe is permanently installed at the low field side
      in the ASDEX Upgrade vacuum vessel and is not subject to limitations in probe
      size, as, for example, probes on a shared manipulator are. The probe is moved by
      a magnetic drive, which allows for easy installation in the vessel, and has
      moderate machine requirements, as it will only require an electric feedthrough
      and an external power supply. The drive gives a linear motion with a radial range
      of 5 cm within 50 ms, where range and velocity can be largely scaled according to
      experimental requirements. The probe has been installed in the outer midplane of
      the ASDEX Upgrade vessel, where ELM filaments are expected to have their maximum
      amplitude. Filaments are coherent substructures within an ELM, carrying a
      fraction of the ELM released energy towards the wall. The new probe allows to
      measure the structure of these filaments, in particular, parameters such as
      filament rotation (by time delay measurements) and size (by peak width analysis).
      Activating the drive moves the probe from a safe position behind the limiter to a
      position in front of the limiters, i.e., exposes the Langmuir pins to the scrape
      off layer plasma.

PMID- 17552816
TI  - Characterization of the diffraction properties of quantum-dot-array diffraction
      grating.
AB  - A new dispersive element named as quantum-dot-array diffraction grating [L. F.
      Cao, China patent No. 200410081499 (August 10, 2004)] for visible light has been
      developed and characterized experimentally. A large number of quantum dots
      distributed on a substrate as sinusoidal function can be used to diffract x rays
      without higher-order diffraction. The experimental patterns show that the higher
      order diffractions which inevitably exist in the spectrum recorded using
      traditional diffraction gratings can be eliminated effectively by this newly
      designed element. It indicates that quantum-dot-array diffraction grating could
      be an attractive alternative of presently used diffraction grating in soft x-ray
      spectroscopy application to get rid of the higher-order diffraction distortions.

PMID- 17552817
TI  - Neutral particle analyzer measurements on the SSPX spheromak.
AB  - A neutral particle analyzer is used to measure the time-resolved energy spectrum
      of neutral hydrogen leaving a spheromak plasma. A gas cell filled with 10-50
      mTorr of helium is used to strip electrons from incoming neutral hydrogen,
      lowering the minimum detectable energy well below that obtained with thin foils.
      Effective neutral particle temperature is calculated by fitting a Maxwellian
      energy distribution to the measured energy spectrum above and below approximately
      300 eV. A computational model with approximated profiles of plasma density and
      neutral density is used with the measured neutral hydrogen flux to estimate the
      ion temperature. Measurement of the power flux due to neutral hydrogen emitted at
      the measurement location is extended to the whole plasma surface to estimate the
      total charge exchange power loss from the plasma. The initial results indicate
      that the charge exchange power loss represents only 2% of the total input gun
      power during the sustainment phase of the discharge.

PMID- 17552818
TI  - Spatiotemporal temperature fluctuation measurements by means of a fast swept
      Langmuir probe array.
AB  - Stationary Langmuir probe measurements of ion saturation current and floating
      potential in a plasma cannot give direct information on density and plasma
      potential fluctuations in the presence of temperature fluctuations. This problem
      can be avoided if the probe bias voltage is continuously swept faster than the
      fluctuation time scale, recording the current-voltage characteristic. This
      article reports the development of a spatiotemporal highly resolving Langmuir
      probe array with 15 fast swept tips, operating in the strongly magnetized,
      collisionless edge plasma of the Wendelstein 7-AS stellarator [Plasma Phys.
      Controlled Fusion 31, 1579 (1989)]. The probe tips are aligned in the poloidal
      direction, the tip spacing is 2 mm, and the sweeping frequency is 1.4 MHz.
      Current and voltage data are sampled with 50 MHz. The high bandwidth of the
      measurement is achieved by placing miniaturized differential amplifiers close to
      the probe tips in order to do an impedance transform. The surface-mounting
      technology and an additional inverse feedback module are utilized, allowing for
      an input voltage range of +/-100 V, and a common mode rejection rate of 55 dB at
      4 MHz, which is sufficient to resolve the nonlinear probe characteristic. For the
      evaluation of the data, a fit model for stationary probes is employed and found
      adequate. Changes of the plasma parameters during one voltage sweep are taken
      into account by a linear interpolation of the fit parameters. Spatio-temporal
      fluctuation data gained by a fast swept Langmuir probe array, which can be
      relevant for the turbulent radial transport of particles and energy, are
      presented.

PMID- 17552819
TI  - Direct quantitative tomographic reconstruction for weakly absorbing homogeneous
      phase objects.
AB  - We examine a direct filtered back projection approach that is suitable for the
      reconstruction of weakly absorbing homogeneous phase objects. Like recent similar
      approaches this method needs only one intensity image in each projection without
      the requirement for an intermediate step of phase retrieval. We tested the method
      using simulation and experimental results. Simulation results show good
      quantitative reconstruction which includes the correct refractive index value and
      distribution of the sample. However, experimental result still indicates the
      presence of artifacts.

PMID- 17552820
TI  - Atomic force microscope nanolithography of polymethylmethacrylate polymer.
AB  - We describe a nanolithography process for a polymethylmethacrylate (PMMA) surface
      using scanning contact atomic force microscopy. Parallel furrows were scribed
      with a pyramidal silicon tip using the same scan mechanism as used to image
      samples. The PMMA was first electron beam irradiated using a scanning electron
      microscope and developed. The topography formed is reproducible and predictable.
      Material from the region where the tip scribes is moved to nearby regions, and
      aligned, elongated PMMA fragments are seen to decorate the valleys between
      furrows.

PMID- 17552821
TI  - Automatization of nanotomography.
AB  - An approach for automated nanotomography, a layer-by-layer imaging technique
      based on scanning probe microscopy (SPM), is presented. Stepwise etching and
      imaging is done in situ in a liquid cell of an SPM. The flow of etching and
      rinsing solutions after each etching step is controlled with solenoid valves
      which allow for an automated measuring protocol. The thermal drift and the drift
      of the piezo scanner is corrected by applying offsets calculated from the cross
      correlation coefficients between successive images. As an example, we have imaged
      human bone with approximately 10 nm resolution using tapping mode SPM and
      successive etching with hydrochloric acid.

PMID- 17552822
TI  - Accurate particle position measurement from images.
AB  - The moment method is an image analysis technique for subpixel estimation of
      particle positions. The total error in the calculated particle position includes
      effects of pixel locking and random noise in each pixel. Pixel locking, also
      known as peak locking, is an artifact where calculated particle positions are
      concentrated at certain locations relative to pixel edges. We report simulations
      to gain an understanding of the sources of error and their dependence on
      parameters the experimenter can control. We suggest an algorithm, and we find
      optimal parameters an experimenter can use to minimize total error and pixel
      locking. For a dusty plasma experiment, we find that a subpixel accuracy of 0.017
      pixel or better can be attained. These results are also useful for improving
      particle position measurement and particle tracking velocimetry using video
      microscopy in fields including colloids, biology, and fluid mechanics.

PMID- 17552823
TI  - Variable-temperature independently driven four-tip scanning tunneling microscope.
AB  - The authors have developed an ultrahigh vacuum (UHV) variable-temperature four
      tip scanning tunneling microscope (STM), operating from room temperature down to
      7 K, combined with a scanning electron microscope (SEM). Four STM tips are
      mechanically and electrically independent and capable of positioning in arbitrary
      configurations in nanometer precision. An integrated controller system for both
      of the multitip STM and SEM with a single computer has also been developed, which
      enables the four tips to operate either for STM imaging independently and for
      four-point probe (4PP) conductivity measurements cooperatively. Atomic-resolution
      STM images of graphite were obtained simultaneously by the four tips.
      Conductivity measurements by 4PP method were also performed at various
      temperatures with the four tips in square arrangement with direct contact to the
      sample surface.

PMID- 17552824
TI  - Feedforward correction of nonlinearities in piezoelectric scanner constructions
      and its experimental verification.
AB  - Piezoelectrical actuators widely used in scanning devices for highly resolved
      displacement generation exhibit a number of known nonlinear effects as hysteresis
      and creep. This article describes an attempt to minimize those nonlinearities by
      recognizing the relation between scan range and voltage magnitude in a scanner
      specific function. In addition, by utilizing a strain gauge sensor system, a
      forward displacement correction is realized. The mathematical procedure behind
      the hysteresis correction is described in detail. The dependence of the higher
      order correction factors on parameters such as scan speed, scan range, or center
      position is studied carefully to extract their influence on the result. Finally,
      integral nonlinearities of about 1% are proven in experiments with an atomic
      force microscope.

PMID- 17552825
TI  - Fiber optic light collection system for scanning-tunneling-microscope-induced
      light emission.
AB  - We report a compact light collection scheme suitable for retrofitting a scanning
      tunneling microscope (STM) for STM-induced light emission experiments. The
      approach uses a pair of optical fibers with large core diameters and high
      numerical apertures to maximize light collection efficiency and to moderate the
      mechanical precision required for alignment. Bench tests indicate that efficiency
      reduction is almost entirely due to reflective losses at the fiber ends, while
      losses due to fiber misalignment have virtually been eliminated. Photon-map
      imaging with nanometer features is demonstrated on a stepped Au(111) surface with
      signal rates exceeding 10(4) counts/s.

PMID- 17552826
TI  - Highly absorbing gadolinium test device to characterize the performance of
      neutron imaging detector systems.
AB  - We report on the fabrication and application of a novel neutron imaging test
      device made of gadolinium. It is designed for a real time evaluation of the
      spatial resolution, resolution direction, and distortions of a neutron imaging
      detector system. Measurements of the spatial resolution of (6)LiF doped ZnS
      scintillator screens with different thicknesses and of imaging plates were
      performed. The obtained results are in good agreement with comparison
      measurements using the standard knife edge detection method.

PMID- 17552827
TI  - Remote in vivo imaging of human skin corneocytes by means of an optical fiber
      bundle.
AB  - Human corneocytes forming the outermost layer of the epidermis (stratum corneum)
      were imaged in vivo by epifluorescence through a coherent optical fiber bundle. A
      very simple and rapid method to remotely visualize the cells forming this
      protective layer of the skin is presented. After the topical application of
      fluorescein, the distal face of an optical fiber bundle is gently applied
      perpendicularly onto the labeled skin (contact mode). Remote fluorescence images
      of the corneocytes are acquired in 50 ms through the bundle comprising 30 000
      individually cladded 3.5 microm diameter optical fibers. The very short focal
      distance which is an intrinsic characteristic of such bundles, allows visualizing
      only the most superficial monolayer of cells in contact with the external
      environment. An image displays about 400-500 cells directly on the human body.
      The size and the arrangement of the corneocytes can thus be acquired and analyzed
      in a very simple and easy way. The method is flexible and can be used for any
      location on the human body. Using a gradient-index lens objective (magnification
      2.8x) fused to the distal face of the bundle allows the shape of the corneocytes
      to be better resolved. In addition, the working distance is 300 microm and hence
      this second approach works in a noncontact imaging mode. Both approaches are
      complementary and allow providing instantaneously either a global view of the
      cells with a possible statistical determination of their area or morphological
      information, which are essential for dermatology and cosmetic sciences. Finally,
      to improve the quality and the contrast of the recorded images, we tested silica
      nanoparticles containing fluorescein. In brief, this diagnostic method is
      nontoxic, painless, easy to use, noninvasive, and nondestructive.

PMID- 17552828
TI  - Compact variable-temperature scanning force microscope.
AB  - A compact design for a cryogenic variable-temperature scanning force microscope
      using a fiber-optic interferometer to measure cantilever deflection is presented.
      The tip-sample coarse approach and the lateral tip positioning are performed by
      piezoelectric positioners in situ. The microscope has been operated at
      temperatures between 6 and 300 K. It is designed to fit into an 8 T
      superconducting magnet with the field applied in the out-of-plane direction. The
      results of scanning in various modes are demonstrated, showing contrast based on
      magnetic field gradients or surface potentials.

PMID- 17552829
TI  - Multifunctional fluorescence correlation microscope for intracellular and
      microfluidic measurements.
AB  - A modified fluorescence correlation microscope (FCM) was built on a commercial
      confocal laser scanning microscope (CLSM) by adding two sensitive detectors to
      perform fluorescence correlation spectroscopy (FCS). A single pinhole for both
      imaging and spectroscopy and a simple slider switch between the two modes thus
      facilitate the accurate positioning of the FCS observation volume after the
      confocal image acquisition. Due to the use of a single pinhole for CLSM and FCS
      the identity of imaged and spectroscopically observed positions is guaranteed.
      The presented FCM system has the capability to position the FCS observation
      volume at any point within the inner 30% of the field of view without loss in
      performance and in the inner 60% of the field of view with changes of FCS
      parameters of less than 10%. A single pinhole scheme for spatial fluorescence
      cross correlation spectroscopy performed on the FCM system is proposed to
      determine microfluidic flow angles. To show the applicability and versatility of
      the system, we measured the translational diffusion coefficients on the upper and
      lower membranes of Chinese hamster ovary cells. Two-photon excitation FCS was
      also realized by coupling a pulsed Ti: sapphire laser into the microscope and
      used for flow direction characterization in microchannels.

PMID- 17552830
TI  - Characterization of power induced heating and damage in fiber optic probes for
      near-field scanning optical microscopy.
AB  - Tip-induced sample heating in near-field scanning optical microscopy (NSOM) is
      studied for fiber optic probes fabricated using the chemical etching technique.
      To characterize sample heating from etched NSOM probes, the spectra of a
      thermochromic polymer sample are measured as a function of probe output power, as
      was previously reported for pulled NSOM probes. The results reveal that sample
      heating increases rapidly to approximately 55-60 degrees C as output powers reach
      approximately 50 nW. At higher output powers, the sample heating remains
      approximately constant up to the maximum power studied of approximately 450 nW.
      The sample heating profiles measured for etched NSOM probes are consistent with
      those previously measured for NSOM probes fabricated using the pulling method. At
      high powers, both pulled and etched NSOM probes fail as the aluminum coating is
      damaged. For probes fabricated in our laboratory we find failure occurring at
      input powers of 3.4+/-1.7 and 20.7+/-6.9 mW for pulled and etched probes,
      respectively. The larger half-cone angle for etched probes ( approximately 15
      degrees for etched and approximately 6 degrees for pulled probes) enables more
      light delivery and also apparently leads to a different failure mechanism. For
      pulled NSOM probes, high resolution images of NSOM probes as power is increased
      reveal the development of stress fractures in the coating at a taper diameter of
      approximately 6 microm. These stress fractures, arising from the differential
      heating expansion of the dielectric and the metal coating, eventually lead to
      coating removal and probe failure. For etched tips, the absence of clear stress
      fractures and the pooled morphology of the damaged aluminum coating following
      failure suggest that thermal damage may cause coating failure, although other
      mechanisms cannot be ruled out.

PMID- 17552831
TI  - High-energy x-ray microbeam with total-reflection mirror optics.
AB  - Total-reflection mirror optics for high-energy x-ray microfocusing have been
      developed, and tested in the energy range of 30-100 keV at beamline 20XU of
      Synchrotron Radiation Facility SPring-8. The optical system consists of a
      Kirkpatrick-Baez-type [J. Opt. Soc. Am. 38, 766 (1548)] focusing optics with
      aspherical total-reflection mirrors for the purpose of reducing the spherical
      aberrations. A focused beam size of 0.35 x 0.4 microm(2) has been achieved at an
      x-ray energy of 80 keV, and the measured spot size was less than 1 microm in the
      x-ray energy region below 90 keV.

PMID- 17552832
TI  - New multichannel electron energy analyzer with cylindrically symmetrical
      electrostatic field.
AB  - This article discusses an electron energy analyzer with a cylindrically
      symmetrical electrostatic field, designed for rapid Auger analysis. The device
      was designed and built. The best parameters of the analyzer were estimated and
      then experimentally verified.

PMID- 17552833
TI  - Phase-locked 10 MHz reference signal for frequency domain time-resolved
      fluorescence measurements.
AB  - A complete electronic system that is suitable for use in megahertz frequency
      domain time-resolved fluorescence instruments based on mode-locked lasers is
      described. The circuit produces a 10 MHz signal, phase locked to the mode-locked
      laser pulse frequency, which is required by many commercial frequency
      synthesizers as the external reference signal. This device is particularly useful
      in conjunction with ultrafast gated intensified charge coupled device cameras
      capable of being frequency modulated for time-resolved fluorescence imaging.

PMID- 17552834
TI  - Tools and strategies for visualization of large image data sets in high
      resolution imaging mass spectrometry.
AB  - Mass spectrometry based proteomics is one of the scientific domains in which
      experiments produce a large amount of data that need special environments to
      interpret the results. Without the use of suitable tools and strategies, the
      transformation of the large data sets into information is not easily achievable.
      Therefore, in the context of the virtual laboratory of enhanced science, software
      tools are developed to handle mass spectrometry data sets. Using different data
      processing strategies for visualization, it enables fast mass spectrometric
      imaging of large surfaces at high-spatial resolution and thus aids in the
      understanding of various diseases and disorders. This article describes how to
      optimize the handling and processing of the data sets, including the selection of
      the most optimal data formats and the use of parallel processing. It also
      describes the tools and solutions and their application in mass spectrometric
      imaging strategies, including new measurement principles, image enhancement, and
      image artifact suppression.

PMID- 17552835
TI  - Wide frequency range capacitive detection of loss in a metallic cantilever using
      resonance and relaxation modes.
AB  - The impedance of a capacitor which embraces a charged cantilever is used to
      measure the mechanical properties of the cantilever material. The technique has
      been tested with an amorphous metallic specimen, but is applicable for many other
      solids. The material damping can be measured at the resonance frequency of the
      cantilever via the width of the resonance curve or by recording the ring-down
      behavior. Additionally, several decades in frequency are accessible below the
      resonance frequency, where values as low as nu=0.03 Hz are achieved easily. The
      data are analyzed with a single equation that captures the damping at all
      frequencies in terms of the material specific Young's modulus E and its loss
      angle tan delta=E"/E'.

PMID- 17552836
TI  - Energy dissipation of materials at high pressure and high temperature.
AB  - We report an experimental method to study the anelastic properties of materials
      at high pressure and high temperature. The multianvil high pressure deformation
      device, used to apply a cyclic loading force onto the sample, can reach 15 GPa
      and 2000 K. A synchrotron x-ray radiation source provides time resolved images of
      the sample and reference material. The images yield stress and strain as a
      function of time; stresses are derived from the reference material, and strains
      from the sample. This method has been tested by applying a sinusoidal stress at
      megahertz to hertz frequency on a San Carlos olivine specimen at 5 GPa and up to
      2000 K. Strain as small as 10(-5) can be resolved. We have obtained experimental
      results which exhibit resolvable attenuation factor (Q(-1)) and shear modulus (M)
      at deep Earth conditions. These results are in quantitative agreement with
      previously reported lower pressure data and suggest that temperature and grain
      size have dominating effect on these properties.

PMID- 17552837
TI  - Simultaneous scanning tunneling microscopy and stress measurements to elucidate
      the origins of surface forces.
AB  - We have developed a new combined measurement system to investigate the underlying
      origins of forces on solid state surfaces from the viewpoint of atomic surface
      morphology. This system consists of two main parts: the measurements of force
      based on displacements and detailed atomic resolution observations of the surface
      morphology. The former involves a large sample cantilever and a capacitive
      detection method that provide sufficient resolution to detect changes of a few
      meV/atom or pN/atom at surfaces. For the latter, a scanning tunneling microscope
      was incorporated to observe structural changes occurring on the surface of the
      cantilever sample. Although this combined observation is not trivial, it was
      accomplished by carefully designing sample dimensions while suppressing the self
      oscillation of the cantilever. To demonstrate the performance of this system a
      preliminary study of the room temperature adsorption of Br(2) on the clean
      Si(111)-7x7 surface is presented.

PMID- 17552838
TI  - Synchrotron x-ray spectroscopy of EuHNO3 aqueous solutions at high temperatures
      and pressures and Nb-bearing silicate melt phases coexisting with hydrothermal
      fluids using a modified hydrothermal diamond anvil cell and rail assembly.
AB  - A modified hydrothermal diamond anvil cell (HDAC) rail assembly has been
      constructed for making synchrotron x-ray absorption spectroscopy, x-ray
      fluorescence, and x-ray mapping measurements on fluids or solid phases in contact
      with hydrothermal fluids up to approximately 900 degrees C and 700 MPa. The
      diamond anvils of the HDAC are modified by laser milling grooves or holes, for
      the reduction of attenuation of incident and fluorescent x rays and sample
      cavities. The modified HDAC rail assembly has flexibility in design for
      measurement of light elements at low concentrations or heavy elements at trace
      levels in the sample and the capability to probe minute individual phases of a
      multiphase fluid-based system using focused x-ray microbeam. The supporting rail
      allows for uniform translation of the HDAC, rotation and tilt stages, and a
      focusing mirror, which is used to illuminate the sample for visual observation
      using a microscope, relative to the direction of the incident x-ray beam. A
      structure study of Eu(III) aqua ion behavior in high-temperature aqueous
      solutions and a study of Nb partitioning and coordination in a silicate melt in
      contact with a hydrothermal fluid are described as applications utilizing the
      modified HDAC rail assembly.

PMID- 17552839
TI  - Experimental setup for low-energy laser-based angle resolved photoemission
      spectroscopy.
AB  - A laser-based angle resolved photoemission (ARPES) system utilizing 6 eV photons
      from the fourth harmonic of a mode-locked Ti:sapphire oscillator is described.
      This light source greatly increases the momentum resolution and photoelectron
      count rate, while reducing extrinsic background and surface sensitivity relative
      to higher energy light sources. In this review, the optical system is described,
      and special experimental considerations for low-energy ARPES are discussed. The
      calibration of the hemispherical electron analyzer for good low-energy angle-mode
      performance is also described. Finally, data from the heavily studied high T(c)
      superconductor Bi(2)Sr(2)CaCu(2)O(8+delta) (Bi2212) is compared to the results
      from higher photon energies.

PMID- 17552840
TI  - Experimental and simulational study of the operation conditions for a high
      transmission mass filter.
AB  - The operation conditions of a double pulsed field mass filter were studied using
      both experiment and simulation. The mass filter consists of two pairs of parallel
      plates and operates on the time-of-flight principle. The study showed that the
      ions' beam deflection angle is a critical factor in optimizing the mass filter
      transmission efficiency. This angle is dependent on the accelerating voltage, ion
      mass, and horizontal velocity of the ions. The optimum operating conditions for
      the mass filter were found and used to study the mass distribution of palladium
      ions produced by a magnetron sputtering source. The study shows that this mass
      filter is suitable for technological applications because of its high
      transmission and wide mass range.

PMID- 17552841
TI  - Simple experimental method for alpha particle range determination in lead iodide
      films.
AB  - An experimental method for determining the range of alpha particles in films
      based on I-V(s) analysis has been suggested. The range of 5.5 MeV alpha particles
      in PbI(2) films determined by this technique is 30+/-5 microm, and this value is
      in agreement with the value calculated by SRIM (the stopping and range of ions in
      matter), r=24 microm in PbI(2). More than 100 I-V(s) of PbI(2) films with
      different thicknesses and quality have been analyzed, and the influence of alpha
      particle radiation on PbI(2) I-V(s) curves has been studied. Developed analytical
      methods (dependence of current density on electric field and conception of
      surface defects) were used, and the method limitations are discussed. It was
      shown that I-V(s) demonstrate the tendency to obey Ohm's law under alpha
      radiation. On the other hand, dark conductivity of the lead iodide films shows a
      typical impure character that can lead to an overestimation of the alpha
      particles' range in PbI(2) films. After films were exposed to alpha radiation,
      the dark resistivity and I-V shape of some films improved. Also, a weak decrease
      of the charge carrier concentration, due to a decrease of the "surface defect"
      concentration ("surface refining"), was registered after successive measurements
      of I-V(s).

PMID- 17552842
TI  - Micromechanical sensor for studying heats of surface reactions, adsorption, and
      cluster deposition processes.
AB  - We present a newly designed highly sensitive micromechanical sensor devoted to
      thermodynamic studies involving supported clusters. The thermally sensitive
      element of the sensor consists of a micromachined silicon cantilever array, onto
      which a thin metal film is evaporated. Due to the difference between the thermal
      expansion coefficients of silicon and the metal employed, thermal bending is
      observed when heat is exchanged with the cantilever. The sensitivity and the
      response time of the cantilever are studied as a function of the film material
      (gold or aluminum) and the thickness of the metal film. With our routinely
      prepared cantilevers, a minimum power of 120 nW is measurable with a
      submillisecond response time, corresponding to a limit of detection in the
      femtojoule range. The high sensitivity of the sensor is demonstrated by measuring
      the heat exchange which occurs during the deposition of clusters on the
      cantilever. Experimentally, we illustrate the 1,3-butadiene hydrogenation
      reaction using a cluster model catalysts created by soft-landing palladium
      clusters onto the cantilever surface.

PMID- 17552843
TI  - Impedance spectroscopy using maximum length sequences: application to single cell
      analysis.
AB  - A maximum length sequence (MLS) is used to perform broadband impedance
      spectroscopy on a dielectric sample. The method has a number of advantages over
      other pulse-based or frequency sweep techniques. It requires the application of a
      very short sequence of voltage steps in the microsecond range and therefore
      allows the measurement of time-dependent impedance of a sample with high temporal
      resolution over a large bandwidth. The technique is demonstrated using a time
      invariant passive RC network. The impedance of single biological cell flowing in
      a microfluidic channel is also measured, showing that MLS is an ideal method for
      high speed impedance analysis.

PMID- 17552844
TI  - Instrument and technique for the in vitro screening of platelet activation from
      whole blood samples.
AB  - The measurement of platelet activation is very difficult to accomplish clinically
      as platelets are readily activated by in vitro manipulations. Although techniques
      such as platelet aggregation and flow cytometry exist to estimate platelet
      function, important limitations prevent these techniques to be widely accepted.
      In this study, low-fouling surfaces used to limit ex vivo platelet activation
      were locally bioactivated to rapidly detect platelet activation from whole blood
      through the selective local adhesion and aggregation of artificially activated
      platelets. To achieve this result, a fabrication method was developed to create
      arrays of anti-CD62 and anti-CD61 proteins covalently immobilized on substrates
      covered by low-fouling graft layers. Moreover, to further limit ex vivo platelet
      activation and to obtain reproducible results, a custom-made flow chamber was
      designed and fabricated with the help of computer-assisted mathematical modeling
      to create defined shear environments. This diagnostic instrument has the
      potential to allow the rapid estimation of platelet activation levels in whole
      blood.

PMID- 17552845
TI  - Recording and interpretation/analysis of tilt signals with five ASKANIA borehole
      tiltmeters at the KTB.
AB  - In June 2003, a large scale injection experiment started at the Continental Deep
      Drilling site (KTB) in Germany. A tiltmeter array was installed which consisted
      of five high resolution borehole tiltmeters of the ASKANIA type, also equipped
      with three dimensional seismometers. For the next 11 months, 86 000 m(3) were
      injected into the KTB pilot borehole 4000 m deep. The average injection rate was
      approximately 200 l/min. The research objective was to observe and to analyze
      deformation caused by the injection into the upper crust at the kilometer range.
      A new data acquisition system was developed by Geo-Research Center Potsdam (GFZ)
      to master the expected huge amount of seismic and tilt data. Furthermore, it was
      necessary to develop a new preprocessing software called PREANALYSE for long
      period time series. This software includes different useful functions, such as
      step and spike correction, interpolation, filtering, and spectral analysis. This
      worldwide unique installation offers the excellent opportunity of the separation
      of signals due to injection and due to environment by correlation of the data of
      the five stations with the ground water table and meteorological data.

PMID- 17552846
TI  - High-temperature superconducting quantum interference device with cooled LC
      resonant circuit for measuring alternating magnetic fields with improved signal
      to-noise ratio.
AB  - Certain applications of superconducting quantum interference devices (SQUIDs)
      require a magnetic field measurement only in a very narrow frequency range. In
      order to selectively improve the alternating-current (ac) magnetic field
      sensitivity of a high-temperature superconductor SQUID for a distinct frequency,
      a single-coil LC resonant circuit has been used. Within the liquid nitrogen bath,
      the coil surrounds the SQUID and couples to it inductively. Copper coils with
      different numbers of windings were used to cover the frequency range from <1 to
      nearly 100 kHz. A superconducting coil made of YBa(2)Cu(3)O(7-delta) tape
      conductor was also tested. With the LC circuit, the signal-to-noise ratio of
      measurements could be improved typically by one order of magnitude or more in a
      narrow frequency band around the resonance frequency exceeding a few kilohertz.
      The best attained equivalent magnetic field resolution was 2.5 fT/radicalHz at 88
      kHz. The experimental findings are in good agreement with mathematical analysis
      of the circuit with copper coil.

PMID- 17552847
TI  - Proposition to build a digitally controlled biphase sinusoidal generator.
AB  - We propose a new method to build a biphase sinusoidal generator which provides
      two signals: v(1)=V(m) sin (omegat) and v(2)=V(m) sin (omegat+phi), where V(m),
      omega, and phi are digitally controlled. Measurements on a prototype confirm the
      analytical calculations. The article relates especially to the phase control.

PMID- 17552848
TI  - Synchronized and configurable source of electrical pulses for x-ray pump-probe
      experiments.
AB  - A method is described for the generation of software tunable patterns of
      nanosecond electrical pulses. The bipolar, high repetition rate (up to 250 MHz),
      fast rise time (<30 ps), square pulses are suitable for applications such as the
      excitation sequence in dynamic pump-probe experiments. Synchronization with the
      time structure of a synchrotron facility is possible as well as fine control of
      the relative delay in steps of 10 ps. The pulse generator described here is used
      to excite magnetic nanostructures with current pulses. Having an excitation
      system which can match the high repetition rate of a synchrotron allows for
      utilization of the full x-ray flux and is needed in experiments which require a
      large photon flux. The fast rise times allow for picosecond time resolution in
      pump-probe experiments. All pulse pattern parameters are configurable by
      software.

PMID- 17552849
TI  - High power, low-noise, and multiply resonant photodetector for interferometric
      gravitational wave detectors.
AB  - We have developed a new photodetector circuit for use in interferometric
      gravitational wave detectors. The circuit can detect high laser power with low
      noise and provide multiple outputs for different signal frequencies. The dynamic
      range of this circuit is increased in comparison with the photodetector design
      used until the end of 2005.

PMID- 17552850
TI  - High resolution gas volume change sensor.
AB  - Changes of gas quantity in a system can be measured either by measuring pressure
      changes or by measuring volume changes. As sensitive pressure sensors are readily
      available, pressure change is the commonly used technique. In many physiologic
      systems, however, buildup of pressure influences the gas exchange mechanisms,
      thus changing the gas quantity change rate. If one wants to study the gas flow in
      or out of a biological gas pocket, measurements need to be done at constant
      pressure. In this article we present a highly sensitive sensor for quantitative
      measurements of gas volume change at constant pressure. The sensor is based on
      optical detection of the movement of a droplet of fluid enclosed in a capillary.
      The device is easy to use and delivers gas volume data at a rate of more than 15
      measurements/s and a resolution better than 0.06 microl. At the onset of a gas
      quantity change the sensor shows a small pressure artifact of less than 15 Pa,
      and at constant change rates the pressure artifact is smaller than 10 Pa or 0.01%
      of ambient pressure.

PMID- 17552851
TI  - Acoustic method for measuring the sound speed of gases over small path lengths.
AB  - Acoustic "phase shift" methods have been used in the past to accurately measure
      the sound speed of gases. In this work, a phase shift method for measuring the
      sound speed of gases over small path lengths is presented. We have called this
      method the discrete acoustic wave and phase detection (DAWPD) method.
      Experimental results show that the DAWPD method gives accurate (+/-3.2 ms) and
      predictable measurements that closely match theory. The sources of uncertainty in
      the DAWPD method are examined and it is found that ultrasonic reflections and
      changes in the frequency ratio of the transducers (the ratio of driving frequency
      to resonant frequency) can be major sources of error. Experimentally, it is shown
      how these sources of uncertainty can be minimized.

PMID- 17552852
TI  - Characterization of hardened cylindrical C1018 steel rods (0.14%-0.2% C, 0.6%
      0.9% Mn) using photothermal radiometry.
AB  - Frequency-domain photothermal radiometry has been used for the evaluation of the
      hardened case depth and the measurement of the thermophysical properties (thermal
      conductivity and diffusivity) of cylindrical C1018 heat-treated steel rods. The
      measurement results of several steel cylinders nominally hardened identically
      during a common heat-treating process were consistent with each other and also
      with mechanical indentation hardness test results. The application of the two
      layer composite cylinder thermal-wave theory yielded an effective case depth
      within the discrete two-layer thermal-wave approximation. This technique provides
      a relatively simple noncontact and nondestructive method for evaluating the
      thermophysical parameters of layered cylindrical samples. The good fit of the
      experimental frequency scans to the two-layer thermal-wave model was shown to
      constitute a reasonable method for calibrating actual continuously decreasing
      hardness depth profiles by means of abrupt two-layer-equivalent profiles.

PMID- 17552853
TI  - Laptop photothermal reflectance measurement instrument assembled with optical
      fiber components.
AB  - In this article, we propose a laptop photothermal reflectance measurement
      instrument assembled with optical fiber components. The primary feature of this
      instrument is that all of the optical routes for the pumping and probing beams,
      as well as the beam sources using a laser diode, are composed of optical fiber
      and optical fiber components. With this configuration, the problems related to
      the technical shortcomings of the conventional instrument can be solved
      completely. Our proposed instrument is also appropriate for in situ measurement
      of the thermoproperties of thin film. The dimensions of our instrument's case are
      400 mm wide, 250 mm deep, and 60 mm tall, and its weight is approximately 1 kg,
      containing the power supply for driving the laser diode of the pumping beam and
      electronics for the detection of photothermal reflectance. These are at least 120
      and 150 smaller than the volume and weight of the conventional commercial
      instrument, respectively. Nevertheless, it is only necessary to prepare a
      synchronous detection instrument for signal recovery (e.g., lock-in amplifier)
      with our instrument. To evaluate our instrument's thermoproperty measurement
      capability, we measured the thermal diffusivity and thermal conductivity of Au
      thin film. The thermal diffusivity of 1.5-microm-thick Au film measured by our
      instrument matched previously reported values within a margin of error of a few
      percent.

PMID- 17552854
TI  - Miniature sensor suitable for electronic nose applications.
AB  - A major research effort has been devoted over the years for the development of
      chemical sensors for the detection of chemical and explosive vapors. However, the
      deployment of such chemical sensors will require the use of multiple sensors
      (probably tens of sensors) in a sensor package to achieve selective detection. In
      order to keep the overall detector unit small, miniature sensors with sufficient
      sensitivity of detection will be needed. We report sensitive detection of
      dimethyl methylphosphonate (DMMP), a stimulant for the nerve agents, using a
      miniature sensor unit based on piezoresistive microcantilevers. The sensor can
      detect parts-per-trillion concentrations of DMMP within 10 s exposure times. The
      small size of the sensor makes it ideally suited for electronic nose
      applications.

PMID- 17552855
TI  - Generic-type hierarchical multi digital signal processor system for hard-field
      tomography.
AB  - This article introduces the design and implementation of a hierarchical multi
      digital signal processor system aimed to perform parallel multichannel
      measurements and data processing of the type widely used in hard-field
      tomography. Details are presented of a complete tomography system with modular
      and expandable architecture, capable of accommodating a variety of data
      processing modalities, configured by software. The configuration of the
      acquisition and processing circuits and the management of the data flow allow a
      data frame rate of up to 250 kHz. Results of a case study, guided path tomography
      for temperature mapping, are shown as a direct demonstration of the system's
      capabilities. Digital lock-in detection is employed for data processing to
      extract the information from ac measurements of the temperature-induced
      resistance changes in an array of 32 noninteracting transducers, which is further
      exported for visualization.

PMID- 17552856
TI  - Highly precise experimental device for determining the heat capacity of liquids
      under pressure.
AB  - An experimental device for making isobaric heat capacity measurements of liquids
      under pressure is presented. The device is an adaptation of the Setaram micro-DSC
      II atmospheric-pressure microcalorimeter, including modifications of vessels and
      a pressure line allowing the pressure in the measurement system to be set,
      controlled, and stabilized. The high sensitivity of the apparatus combined with a
      suitable calibration procedure allows very accurate heat capacity measurements
      under pressure to be made. The relative uncertainty in the isobaric molar heat
      capacity measurements provided by the new device is estimated to be 0.08% at
      atmospheric pressure and 0.2% at higher levels. The device was validated from
      isobaric molar heat capacity measurements for hexane, nonane, decane, undecane,
      dodecane, and tridecane, all of which were highly consistent with reported data.
      It also possesses a high sensitivity as reflected in its response to changes in
      excess isobaric molar heat capacity with pressure, which were examined in this
      work for the first time by making heat capacity measurements throughout the
      composition range of the 1-hexanol+n-hexane system. Finally, preliminary
      measurements at several pressures near the critical conditions for the
      nitromethane+2-butanol binary system were made that testify to the usefulness of
      the proposed device for studying critical phenomena in liquids under pressure.

PMID- 17552857
TI  - Application of a fast electrical pulse in gated multichannel plate camera.
AB  - An eight-frame gated microchannel plate (MCP) camera and a gating electrical
      pulse are described in this article. The gating electrical pulse is obtained by
      first generating a high voltage fast step pulse using avalanche transistors in
      Marx bank configuration, and then shaping it using avalanche diodes. The high
      voltage fast step pulse is about 200 ps in fall time and 4 kV in amplitude. The
      gating pulse wave form with width of 160 ps and amplitude of 2.5 kV is achieved.
      Each frame photocathode coated with gold on the MCP is part of a 12 Omega
      transmission line with open circuit end driven by the gating electrical pulse.
      The camera is tested by illuminating its photocathode with ultraviolet laser
      pulses, 266 nm in wavelength, which shows exposure time as short as 120 ps.

PMID- 17552858
TI  - Air-coupled acoustic method for testing and evaluation of microscale structures.
AB  - A noncontact testing and characterization approach for microscale structures
      based on air-coupled acoustic excitation and optical sensing is proposed and
      demonstrated. Using an air-coupled transducer to externally excite and a laser
      Doppler vibrometer/interferometer to capture transient displacement wave forms,
      the experimental approach results in a technique to determine mechanical
      properties of microscale structural elements. The effectiveness of this method
      has been demonstrated on commercially available microcantilever beams and
      microscale rotational oscillators fabricated for this study. The resonance
      frequencies and mechanical properties (Young's modulus and stiffness) extracted
      from the transient displacement wave forms have been compared, with good
      agreement, to computational and simplified analytical models for each case. It is
      also shown that the technique could serve to diagnose stiction problems of
      microscale structures. Some potential advantages of the approach described
      include the simplicity of the test setup, functionality at room conditions,
      noncontact and nondestructive operations, and repeatability and rapid turn-around
      time for the evaluation of modal parameters and mechanical properties of
      microscale structures.

PMID- 17552859
TI  - Improving the reliability of multiplexed fiber optic low-coherence
      interferometric sensors by use of novel twin-loop network topologies.
AB  - Novel twin-loop network topologies for multiplexing fiber optic low-coherence
      reflectometric sensors are proposed and theoretically analyzed. The sensing
      fibers are made by connecting segments of standard single-mode fibers with
      partial reflections at the fiber joints and are completely passive. Absolute
      length measurement can be made for each segment of the sensing fiber so that
      strain or temperature distribution along the entire sensing fiber can be derived.
      It is expected that novel topologies would help as to improve the reliability of
      the sensor network by providing multiple accesses to each of the sensing segment
      so that most of the sensing segments can still be interrogated even when one or
      more point breakages occur along the transmission fibers. A nine-sensor twin-loop
      sensing network was constructed and experimentally tested by use of a Michelson
      low-coherence interferometer, and the results obtained agree with our theoretical
      prediction. The novel network topologies may be used for large-scale smart
      structure applications where breakages of transmission fibers may occur during
      the stages of sensor imbedding, installation, and structure-in-service cycles.

PMID- 17552860
TI  - Interstellar dust laser explorer: a new instrument for elemental and isotopic
      analysis and imaging of interstellar and interplanetary dust.
AB  - We present the performance characteristics of a time-of-flight secondary ion mass
      spectrometer designed for 157 nm laser postionization of sputtered neutrals for
      high sensitivity elemental and isotopic analyses. The instrument was built with
      the aim of analyzing rare element abundances in micron to submicron samples such
      as interstellar grains and cometary dust. Relative sensitivity factors have been
      determined for secondary ion mass spectrometry which show an exponential
      dependency against the first ionization potential. This allows elemental
      abundances to be measured with errors below 25% for most major elements. The
      accuracy for isotope ratios, where isotopes can be resolved from isobaric
      interferences, is usually limited only by counting statistics. In laser secondary
      neutral mass spectrometry, the spatial and temporal overlaps between the laser
      and sputtered neutral atoms are modeled and predictions of total detection
      efficiency and isotopic and elemental fractionation are compared with
      experimental data. Relative sensitivity factors for laser-ionized secondary
      neutrals from a stainless steel standard are found to vary less than 3% above
      saturation laser pulse energy enabling more accurate quantification.

PMID- 17552861
TI  - Simple synchronic detection at audio frequencies through a PC sound card.
AB  - We present a simple personal computer based, synchronic detection system that
      emulates a lock-in amplifier at audio frequencies. The inputs of the sound card
      are used to acquire two sets of samples: the one to be measured, previously
      preamplified, and the reference. From the last one, two "quasiorthogonal" signals
      are derived to perform dual-phase detection. The procedure is fast and compares
      favorably with a benchtop lock-in amplifier. In the band from 100 Hz to 20 kHz we
      obtained average amplitude and phase errors below 1% and 0.1 degrees,
      respectively.

PMID- 17552862
TI  - Quadruple-bend achromatic low emittance lattice studies.
AB  - A quadruple-bend achromatic (QBA) cell, defined as a supercell made of two double
      bend cells with different outer and inner dipole bend angles, is found to provide
      a factor of 2 in lowering the beam emittance relative to the more conventional
      double-bend achromat. The ratio of bending angles of the inner dipoles to that of
      the outer dipoles is numerically found to be about 1.5-1.6 for an optimal low
      beam emittance in the isomagnetic condition. The QBA lattice provides an
      advantage over the double-bend achromat or the double-bend nonachromat in
      performance by providing a small natural beam emittance and some zero-dispersion
      straight sections. A lattice with 12 QBA cells and a preliminary dynamic aperture
      study serves as an example.

PMID- 17552863
TI  - Protecting a lens with air.
AB  - A novel design is the concept of preventing the camera lens from contamination of
      the particles by using "airwall." An experimental wireless video camera debris
      deflecting system was realized and performed to verify the concept. Functional
      tests have been successfully verified.

PMID- 17552864
TI  - Focal-plane imaging of crossed beams in nonlinear optics experiments.
AB  - An application of focal-plane imaging that can be used as a real time diagnostic
      of beam crossing in various optical techniques is reported. We discuss two
      specific versions and demonstrate the capability of maximizing system performance
      with an example in a combined dual-pump coherent anti-Stokes Raman scattering
      interferometric Rayleigh scattering experiment (CARS-IRS). We find that this
      imaging diagnostic significantly reduces beam alignment time and loss of CARS-IRS
      signals due to inadvertent misalignments.

PMID- 17552865
TI  - Fast response of InSb Schottky detector.
AB  - An InSb Schottky detector, fabricated from an undoped InSb wafer with Hall
      mobility which is higher than those of previously employed InSb wafers, was used
      for alpha particle detection. The output pulse of this InSb detector showed a
      very fast rise time, which was comparable with the output pulses of scintillation
      detectors.

PMID- 17552866
TI  - Reversible, high-voltage square-wave pulse generator for triggering spark gaps.
AB  - A design is presented for a reversible, square-pulse generator that employs
      coaxial cables for charge storage and pulse formation and a thyratron as the
      switch. The generator has a nominal output voltage of 5-30 kV and a pulse
      duration determined by the cable's physical length. Two variations are presented:
      (1) a single-stage one consisting of cable that is charged via its shield on one
      end and discharged with a thyratron on the opposite end and (2) a two-stage one
      having an inverting circuit that uses a coaxial cable to reverse the polarity of
      the pulse. The generator operates with "flying shields," i.e., high-voltage
      pulses also propagate on the outside of the cables; this calls for a dedicated
      insulation that avoids breakdown between sections of the cable's shield. The rise
      time obtained is mostly dictated by the switching time of the thyratron; with the
      one we used in the tests, rise times in the range of 30-40 ns were obtained. We
      present the results obtained in the implementation of the generators as well as
      its application to fire a large Marx generator.

PMID- 17552867
TI  - Pulsed wire discharge apparatus for mass production of copper nanopowders.
AB  - A pulsed wire discharge (PWD) apparatus for the mass production of nanopowders
      has been developed. The apparatus has a continuous wire feeder, which is operated
      in synchronization with a discharging circuit. The apparatus is designed for
      operation at a maximum repetition rate of 1.4 Hz at a stored energy of 160 J. In
      the present study, Cu nanopowder was synthesized using the PWD apparatus and the
      performance of the apparatus was examined. Cu nanopowder of 2.0 g quantity was
      prepared in N(2) gas at 100 kPa for 90 s. The particle size distribution of the
      Cu nanopowder was analyzed by transmission electron microscopy and the mean
      surface diameter was determined to be 65 nm. The ratio of the production mass of
      the powder to input energy was 362 g/kW h.

PMID- 17552869
TI  - Targeted deletion of MMP-9 attenuates myocardial contractile dysfunction in heart
      failure.
AB  - Chronic volume overload (VO) on the left ventricle (LV) augments redox stress and
      activates matrix metalloproteinase (MMP) which causes the endocardial endothelial
      myocyte (EM) disconnection leading to myocardial contractile dysfunction. VO
      induced MMP-9 activation impairs cardiac functions, in part by endothelial
      endocardial apoptosis, but the role of MMP-9 on EM functions remains obscure. We
      conjecture that chronic VO activates MMP-9 and causes EM uncoupling.
      Arteriovenous fistula (AVF) was created in genetically identical wild type (WT)
      mice (FVB/NJ) and MMP-9 knockout mice (MMP-9KO, FVB.Cg-MMP9(tm1Tvu)/J). Sham
      operated mice were used as controls. Before experimentation the phenotype
      analysis of MMP-9KO mice was carried out. In-gel-gelatin zymography for MMP-9
      activation was performed on LV homogenates. The EM functions were determined on
      LV rings using tissue myobath. We report a decrease in MMP-9 activity in left
      ventricular myocardial extracts in MMP-9 deficient mice after AVF. The responses
      to drugs affecting cardiac functions (acetylcholine (Ach), nitroprusside and
      bradykinin) were attenuated in AVF mice suggesting the impairment of EM coupling.
      Interestingly, the EM functions were restored in the MMP-9 deficient mice after
      AVF. We suggest a direct cause-and-effect relationship between MMP-9 activation
      and EM uncoupling in LV myocardium after chronic VO and the possible involvement
      of MMP-9 in myocardial contractile performance.

PMID- 17552870
TI  - Different functional responsibility of the small intestine to high-fat/high
      energy diet determined the expression of obesity-prone and obesity-resistant
      phenotypes in rats.
AB  - The objective of the present experiment was to assess the involvement of small
      intestine in expression of susceptibility or resistance to the high-fat/high
      energy diet. The investigation was carried out in adult male Sprague-Dawley rats
      fed either standard laboratory diet (3.2 kcal/g, 9.5 % fat) or high-fat (HF) diet
      (4.04 kcal/g, 30 % fat) for 4 weeks as well as in HF rats that were
      retrospectively designated on the bases of their higher or lower weight gain as
      sensitive (DIO) or resistant (DR) to obesity. Our results revealed in HF group
      significant increase in energy intake, food efficiency, weight gain and Lee s
      index of obesity. Moreover, in comparison with controls, a significantly
      increased duodenal and jejunal alkaline phosphatase (AP) and alpha-glucosidase
      activity as well as hypertrophy of jejunal mucosa (increased protein/DNA ratio)
      were observed in HF fed rats. In contrast, intestinal function was inversely
      related to energy intake or to the development of adiposity in DIO vs. DR rats.
      The DR rats had significantly greater AP and alpha-glucosidase activity and more
      pronounced suppression of energy intake than obese DIO rats. It indicates that
      the increase of enzyme activities and the lowered effectiveness of nutrient
      absorption might be a significant factor preventing the expression of obesity
      proneness. This information contributes to a better understanding of a complex
      interaction between HF diet feeding and small intestinal adaptability, which
      determines the energy homeostasis and predict the ability to resist or develop
      obesity in these phenotypes.

PMID- 17552871
TI  - An evidence for regulatory cross-talk between aryl hydrocarbon receptor and
      glucocorticoid receptor in HepG2 cells.
AB  - Aryl hydrocarbon receptor (AhR) and glucocorticoid receptor (GR) play crucial
      role in the regulation of drug metabolizing enzymes and in many essential
      physiological processes. Cellular signaling by these receptors shares several
      functional and regulatory features. Here we investigated regulatory cross-talk
      between these two receptors. Human hepatoma cells (HepG2) were the model of
      choice. We analyzed the effects of dexamethasone (DEX) and dioxin (TCDD) on i)
      expression of AhR and GRalpha mRNAs; ii) levels of AhR and GR proteins; iii)
      transcriptional activities of AhR and GR in reporter assays; iv) 7
      ethoxyresorufin-O-deethylase activity (EROD). We found that both DEX and TCDD
      affected AhR and GR mRNAs expression, proteins levels and transcriptional
      activities in HepG2 cells. These effects on cellular signaling by AhR and GR
      comprised up-/down-regulation of gene expression and ligand-dependent protein
      degradation. We conclude that interactive regulatory cross-talk between GR and
      AhR receptors in HepG2 cells defines possible implications in physiology and drug
      metabolism. Future research should be focused on the investigation of AhR-GR
      cross-talk in various normal human cells and tissues both in vitro and in vivo.

PMID- 17552873
TI  - Overweight and decreased baroreflex sensitivity as independent risk factors for
      hypertension in children, adolescents, and young adults.
AB  - We studied the relationship between blood pressure (BP), body mass index (BMI,
      kg/m(2)) and baroreflex sensitivity (BRS, ms/mmHg) in adolescents. We examined 34
      subjects aged 16.2+/-2.4 years who had repeatedly high causal BP (H) and 52
      controls (C) aged 16.4+/-2.2 years. Forty-four C and 22 H were of normal weight
      (BMI between 19-23.9), and 8 C and 12 H were overweight (BMI between 24-30).
      Systolic BP was recorded beat-to-beat for 5 min (Finapres, controlled breathing
      0.33 Hz). BRS was determined by the cross-spectral method. The predicting power
      of BMI and BRS for hypertension was evaluated by sensitivity, specificity, and
      receiver operating curve (ROC - plot of sensitivity versus specificity). H
      compared with C had lower BRS (p<0.01) and higher BMI (p<0.05). Multiple logistic
      regression analysis (p<0.001) revealed that a decreased BRS (p<0.05) and an
      increased BMI (p<0.01) were independently associated with an increased risk of
      hypertension. No correlation between BMI and BRS was found either in H or in C.
      Following optimal critical values by ROC, the sensitivity, specificity and area
      under ROC were determined for: BMI - 22.2 kg/m(2), 61.8 %, 69.2 %, 66.0 %; BRS -
      7.1 ms/mmHg, 67.7 %, 69.2 %, 70.0 %; BMI and BRS - 0.439 a.u., 73.5 %, 82.7 %,
      and 77.3 %. Decreased BRS and overweight were found to be independent risk
      factors for hypertension.

PMID- 17552872
TI  - Plasma procalcitonin in patients with ileus. Relations to other inflammatory
      parameters.
AB  - Plasma procalcitonin (PCT) is a highly specific marker for the diagnosis of
      bacterial infections and sepsis. PCT levels are usually low in viral infections,
      chronic inflammation or postsurgical states. The purpose of this study was to
      characterize PCT plasma levels in patients with various types of ileus at
      preoperative stage, where the other inducing factors such as a surgical stress
      are excluded. The prospective study was performed on 54 patients admitted to in
      patient surgical department with a proven diagnosis of ileus. Patients were
      divided to three groups--obstructive, vascular and paralytic ileus. Plasma levels
      of PCT (Kryptor analysis), TNFalpha, IL-1beta, IL-6, cortisol (ELISA) and CRP
      (Kryptor ultrasensitive analysis) were estimated before any invasive procedure
      was realized. We demonstrated significant elevation of PCT in both obstructive
      ileus in adhesions and vascular ileus compared with healthy subjects (p 0.01).
      PCT levels were not elevated in paralytic ileus. The regression coefficient was
      the highest for PCT and CRP (r=0.78, p 0.01), for TNFalpha and IL-8 (r=0.76, p
      0.01) in vascular ileus. There was no significant correlation between PCT and
      other inflammatory parameters. The different types of ileus induce an elevation
      of plasma PCT levels and PCT shows itself as an acute phase reactant. The highest
      PCT concentrations were presented in patients with vascular ileus, whereas
      paralytic ileus revealed similar cytokine and PCT pattern as in healthy subjects.
      Plasma PCT estimation extended to a measurement of CRP and IL-6 may become a
      useful complementary examination for diagnostics of acute abdomen in patients.

PMID- 17552874
TI  - Immunological response in the mouse melanoma model after local hyperthermia.
AB  - Our study was aimed to characterize the phenotype and functional endpoints of
      local microwave hyperthermia (LHT, 42 degrees C) on tumor infiltrating and spleen
      leukocytes. The effectiveness of LHT applied into the tumor of B16F10 melanoma
      bearing C57/BL6 mice was compared with anesthetized and non-treated animals.
      Subpopulations of leukocytes were analyzed using the flow cytometry, and the
      cytotoxic activity of splenocytes against syngeneic B16F10 melanoma and NK
      sensitive YAC-1 tumor cell lines was evaluated in (51)Cr-release assay.
      Similarly, the in vitro modification of the heat treatment was performed using
      healthy and melanoma-bearing splenocytes. We found a 40 % increase of activated
      monocytes (CD11b+CD69+) infiltration into the tumor microenvironment. In the
      spleen of experimental animals, the numbers of cytotoxic T lymphocytes (CTLs
      CD3+CD8+) and NK cell (CD49b+NK1.1+) raised by 22 % and 14 %, respectively, while
      the NK1.1+ monocytes decreases by 37 %. This was accompanied by an enhancement of
      cytotoxic effector function against B16F10 and YAC-1 targets in both in vivo and
      in vitro conditions. These results demonstrate that LHT induces better killing of
      syngeneic melanoma targets. Furthermore, LHT evokes the homing of activated
      monocytes into the tumor microenvironment and increases the counts of NK cells
      and CTL in the spleen.

PMID- 17552875
TI  - Effect of somatostatin on repair of ionizing radiation-induced DNA damage in
      pituitary adenoma cells GH3.
AB  - Ionizing radiation and somatostatin analogues are used for acromegaly treatment
      to achieve normalization or reduction of growth hormone hypersecretion and tumor
      shrinkage. In this study, we investigated a combination of somatostatin (SS14)
      with ionizing radiation of (60)Co and its effect on reparation of radiation
      induced damage and cell death of somatomammotroph pituitary cells GH3. Doses of
      gamma-radiation 20-50 Gy were shown to inhibit proliferation and induce apoptosis
      in GH3 cells regardless of somatostatin presence. It has been found that the D(0)
      value for GH3 cells was 2.5 Gy. Somatostatin treatment increased radiosensitivity
      of GH3 cells, so that D(0) value decreased to 2.2 Gy. We detected quick
      phosphorylation of histone H2A.X upon irradiation by the dose 20 Gy and its
      colocalization with phosphorylated protein Nbs-1 in the site of double strand
      break of DNA (DSB). Number of DSB decreased significantly 24 h after irradiation,
      however, clearly distinguished foci persisted, indicating non repaired DSB, after
      irradiation alone or after combined treatment by irradiation and SS14. We found
      that SS14 alone triggers phosphorylation of Nbs1 (p-Nbs1), which correlates with
      antiproliferative effect of SS14. Irradiation also increased the presence of p
      Nbs1. Most intensive phosphorylation of Nbs1 was detected after combined
      treatment of irradiation and SS14. The decrease of the number of the DSB foci 24
      h after treatment shows a significant capacity of repair systems of GH3 cells. In
      spite of this, large number of unrepaired DSB persists for 24 h after the
      treatment. We conclude that SS14 does not have a radioprotective effect on
      somatomammotroph GH3 cells.

PMID- 17552876
TI  - Liver glucocorticoid receptor and heat shock protein 70 levels in rats exposed to
      different stress models.
AB  - The aim of the present study was to define the stress-induced pattern of
      cytosolic glucocorticoid receptor (GR) and Hsp70 protein in the liver of male
      Wistar rats exposed to different stress models: acute (2 h/day) immobilization or
      cold (4 degrees C); chronic (21 days) isolation, crowding, swimming or isolation
      plus swimming and combined (chronic plus acute stress). Changes in plasma levels
      of corticosterone were studied by radioimmunoassay (RIA). The results obtained by
      Western immunoblotting showed that both acute stressors led to a significant
      decrease in cytosolic GR and Hsp70 levels. Compared to acute stress effects, only
      a weak decrease in the levels of GR and Hsp70 was demonstrated in chronic stress
      models. Chronically stressed rats, which were subsequently exposed to novel acute
      stressors (immobilization or cold), showed a lower extent of GR down-regulation
      when compared to acute stress. The exception was swimming, which partially
      restores this down-regulation. The observed changes in the levels of these major
      stress-related cellular proteins in liver cytosol lead to the conclusion that
      chronic stressors compromise intracellular GR down-regulation in the liver.

PMID- 17552877
TI  - Urinary urea nitrogen excretion during the hyperinsulinemic euglycemic clamp in
      type 1 diabetic patients and healthy subjects.
AB  - The hyperinsulinemic euglycemic clamp (HEC) combined with indirect calorimetry
      (IC) is used for estimation of insulin-stimulated substrate utilization.
      Calculations are based on urinary urea nitrogen excretion (UE), which is
      influenced by correct urine collection. The aims of our study were to improve the
      timing of urine collection during the clamp and to test the effect of insulin on
      UE in patients with type 1 diabetes (DM1; n=11) and healthy subjects (C; n=11).
      Urine samples were collected (a) over 24 h divided into 3-h periods and (b)
      before and during two-step clamp (1 and 10 mIU.kg(-1).min(-1); period 1 and
      period 2) combined with IC. The UE during the clamp was corrected for changes in
      urea pool size (UEc). There were no significant differences in 24-h UE between C
      and DM1 and no circadian variation in UE in either group. During the clamp, serum
      urea decreased significantly in both groups (p<0.01). Therefore, UEc was
      significantly lower as compared to UE not adjusted for changes in urea pool size
      both in C (p<0.001) and DM1 (p<0.001). While UE did not change during the clamp,
      UEc decreased significantly in both groups (p<0.01). UEc during the clamp was
      significantly higher in DM1 compared to C both in period 1 (p<0.05) and period 2
      (p<0.01). The UE over 24 h and UEc during the clamp were statistically different
      in both C and DM1. We conclude that urine collection performed during the clamp
      with UE adjusted for changes in urea pool size is the most suitable technique for
      measuring substrate utilization during the clamp both in DM1 and C. Urine
      collections during the clamp cannot be replaced either by 24-h sampling (periods
      I-VII) or by a single 24-h urine collection. Attenuated insulin-induced decrease
      in UEc in DM1 implicates the impaired insulin effect on proteolysis.

PMID- 17552878
TI  - Meloxicam, an inhibitor of cyclooxygenase-2, increases the level of serum G-CSF
      and might be usable as an auxiliary means in G-CSF therapy.
AB  - Hematopoiesis-modulating action of meloxicam, a cyclooxyge-nase-2 inhibitor, has
      been evaluated in mice. Increased serum level of granulocyte colony-stimulating
      factor (G-CSF) after meloxicam administration has been found in sublethally gamma
      irradiated animals. In further experiments hematopoiesis-stimulating effects of
      meloxicam and G-CSF given alone or in combination have been investigated.
      Granulocyte/macrophage progenitor cells counts were used to monitor these
      effects. Meloxicam and exogenous G-CSF did not act synergistically when given in
      combination, but could be mutually substituted during their repeated
      administration. The results suggest a promising possibility of using meloxicam as
      an auxiliary drug reducing the high costs of G-CSF therapy of myelosuppression.

PMID- 17552879
TI  - Nitric oxide and prostaglandins - important players in endothelin-1 induced
      myocardial distensibility.
AB  - This study investigated whether endothelin (ET)-1-induced increase in myocardial
      distensibility is preserved in heart failure (HF) and whether it is modulated by
      nitric oxide (NO) and prostaglandins. New Zealand white rabbits were treated with
      doxorubicin (1 mg/kg, intravenously twice a week for 8 weeks, DOX-HF group) or
      saline (control group). Effects of ET-1 (0.1, 1, 10 nM) were tested in papillary
      muscles from the DOX-HF group and a control group in the presence of: i) intact
      endocardial endothelium (EE); ii) damaged EE; iii) N(G)-nitro-L-arginine (L-NNA;
      NO synthase inhibitor), and iv) indomethacin (INDO; cyclooxygenase inhibitor). In
      the presence of an intact EE, ET-1 promoted concentration-dependent positive
      inotropic and lusitropic effects that were maintained after damaging the EE, in
      the presence of L-NNA or INDO and in the DOX-HF Group. ET-1 reduced resting
      tension at the end of the isometric twitch (increased diastolic distensibility)
      by 3.2+/-1.3 %, 6.0+/-1.6 % and 8.8+/-2.7 % (at 0.1, 1 and 10 nM, respectively),
      in muscles with intact EE, effect that was completely abolished after damaging
      EE, in the presence of L-NNA or INDO or in the DOX-HF Group. This study
      demonstrated that the increase in myocardial distensibility induced by ET-1 is
      absent in HF and is dependent of NO and prostaglandin release.

PMID- 17552880
TI  - Calcium intake and the outcome of short-term weight management.
AB  - Experimental and epidemiological studies suggest that calcium intake is inversely
      related to weight gain. Calcium of dairy origin has been shown to be more
      effective in promoting weight loss. However, clinical studies yielded
      controversial results concerning the role of calcium intake in weight change. The
      aim of this study was to ascertain whether the addition of calcium can affect the
      outcome of 3-week weight management (WM) with a hypocaloric diet characterized by
      a decreased calcium intake. Overweight/ obese women (n=67; BMI 32.2+/-4.1
      kg/m(2); age 49.1+/-12.1 years) underwent a 4-week comprehensive WM program. WM
      included a 7 MJ/day diet resulting in a stable weight during the first week and a
      4.5 MJ/day diet with mean daily calcium intake 350 mg during the second to fourth
      week. Participants were divided into three age- and BMI-matched groups who
      received placebo or calcium (500 mg/day). Calcium was administered either as
      carbonate or calcium of dairy origin (Lactoval). There was no significant
      difference in weight loss in response to WM between the placebo-treated and
      calcium-treated groups. However, addition of calcium to the diet resulted in a
      lower hunger score in the Eating Inventory as well as a decrease in plasma
      resistin levels. Body composition measured by bioimpedance demonstrated that
      added calcium leads to preservation of fat-free mass. Nevertheless, a greater
      loss of fat-free mass in the placebo group might be partly due to a greater loss
      of water.

PMID- 17552881
TI  - Dendritic cells and T lymphocyte interactions in patients with lymphoid
      malignancies.
AB  - Dendritic cell (DC) vaccination is an attractive approach to the treatment of
      patients with lymphoid tumors. To evaluate its feasibility, we have tested the
      functional properties of DC and T-lymphocytes in patients with treated and
      untreated chronic lymphocytic leukemia (CLL) and follicular lymphoma (FL).
      Healthy volunteers were used both as controls and as a source of cells for
      allogeneic mixed leukocyte reaction (MLR). In these reactions, dendritic cells
      from both untreated and treated patients were comparable to dendritic cells from
      healthy volunteers. In all the untreated patients studied, autologous dendritic
      cells promoted the survival and proliferation of both CD4 and CD8 lymphocytes
      (though the proliferation response was much better in the CD4 subset), whereas
      only 3 out of 5 treated patients were able to mount this response with CD4
      lymphocytes and 4 out of 5 with CD8 lymphocytes. In 3 out of 5 untreated
      patients, pulsing of DCs with tetanus toxoid promoted a better CD4 response than
      was achieved with unpulsed DCs, while none of 5 treated patients had an
      additional response after pulsing with tetanus toxoid. None of patients studied,
      either treated or untreated, had a better CD8 response to pulsed DCs than to
      unpulsed ones. During CD4 lymphocyte proliferation, more CD4(+)CD25(hi)
      lymphocytes were generated in both treated and untreated patients than in healthy
      controls. Poor proliferation of cytotoxic cells and preferential proliferation of
      CD4(+)CD25(hi) T-regulatory cells in response to self and/or foreign antigens
      might be one of the mechanisms responsible for immunosuppression and impaired
      tumor surveillance in patients with lymphoid malignancies.

PMID- 17552882
TI  - The time-course of agonist-induced solubilization of trimeric
      G(q)alpha/G(11)alpha proteins resolved by two-dimensional electrophoresis.
AB  - Prolonged agonist stimulation results in specific transfer of activated Galpha
      subunits of G(q)alpha/G(11)alpha family from particulate membrane fraction to
      soluble (cytosol) cell fraction isolated as 250,000 x g supernatant. In this
      study, we have used 2D electrophoresis for more defined resolution of Galpha
      subunits of G(q)alpha/G(11)alpha family and followed the time course of
      solubilization effect. The small signal of soluble G proteins was already
      detected in control, hormone-unexposed cells. Hormone stimulation resulted in a
      slow but continuous increase of both intensity and number of immunoreactive
      signals/spots of these G proteins (10, 30, 60, 120 and 240 min). At longer times
      of agonist exposure (>2 hours), a marked increase of G(q)alpha/G(11)alpha
      proteins was detected. The maximal level of soluble G(q)alpha/G(11)alpha proteins
      was reached after 16 hours of continuous agonist exposure. At this time interval,
      eight individual immunoreactive signals of G(q)alpha/G(11)alpha proteins could be
      resolved. The relative proportion among these spots was 15:42:10:11:7:7:2:5.
      Solubilization of this class of Galpha proteins was thus observed after prolonged
      agonist stimulation only, induced by ultra high concentration of hormone and in
      cells expressing a large number of GPCRs. Our data therefore rather indicate
      tight/persisting binding of G(q)alpha/G(11)alpha proteins to the membrane.

PMID- 17552883
TI  - Comparative modeling of the H4-H5-loop of the alpha2-isoform of Na+/K+-ATPase
      alpha-subunit in the E1 conformation.
AB  - Restraint-based comparative modeling was used for calculation and visualization
      of the H4-H5-loop of Na+/K+-ATPase from mouse brain (Mus musculus, adult male
      brain, alpha2-isoform) between the amino acid residues Cys 336 and Arg 758 in the
      E1 conformation The structure consists of two well separated parts. The N-domain
      is formed by a seven-stranded antiparallel beta-sheet with two additional beta
      strands and five alpha-helices sandwiching it, the P-domain is composed of a
      typical Rossman fold. The ATP-binding site was found on the N-domain to be
      identical in both alpha2- and alpha1-isoforms. The phosphorylation Asp 369
      residue was found in the central part of the P-domain, located at the C-terminal
      end of the central beta-sheet. The distance between the alpha-carbon of Phe 475
      at the ATP-binding site and the alpha-carbon of Asp 369 at the phosphorylation
      site is 3.22 nm. A hydrogen bond between the oxygen atom of Asp 369 and the
      nitrogen atom of Lys 690 was clearly detected and assumed to play a key role in
      maintaining the proper structure of the phosphorylaton site in E1 conformation.

PMID- 17552884
TI  - Noninvasive assessment of local myocardium repolarization changes using high
      resolution surface ECG mapping.
AB  - A method using body surface potential maps for assessment of myocardium lesions
      with changed repolarization is presented and suitable mapping system is
      introduced. Differences between normal and altered QRST integral maps together
      with torso volume conductor model were used to determine the equivalent dipole
      representing the lesion. Performance of the method was studied on simulated data.
      Changed repolarization was modeled by shortening of myocyte action potentials in
      regions typical for stenosis of the main coronary arteries. The equivalent dipole
      estimated the positions of small lesions with a mean error of 9+/-4 mm (17+/-14
      mm for larger transmural lesions). The subepicardial or subendocardial character
      of the lesions was reflected in the dipole orientation. Tests of the method on
      patients after myocardial infarction that underwent coronary intervention on a
      single coronary vessel showed that in 7 of 8 successfully treated patients the
      dipole position matched well with the treated vessel. A small dipole moment in
      another patient indicated unsuccessful treatment. The method was implemented in a
      new 128-channel mapping system. Its active electrodes, battery powered measuring
      unit and optical computer interface help to minimize noise in ECG and guarantee
      patient's safety. The results suggest that the method and mapping system offer
      useful tools for noninvasive identification of local repolarization changes in
      the myocardium.

PMID- 17552885
TI  - Dependence of the vulnerability index on the heart cycle length.
AB  - Index of vulnerability is a parameter based on ventricular gradient evaluating
      the risk of arrhythmia development. The index is derived from isointegral maps of
      the QT interval. Individual characteristics of isointegral maps are influenced by
      different factors, which contribute to the relatively high variability among
      measured parameters of maps in measured subjects. While several
      electrocardiographic indexes have been introduced, there are only few studies of
      their dependence on heart rate. In this study we set out to establish the
      dependence of vulnerability index on the RR interval or heart rate in healthy
      population. A positive linear correlation between RR intervals and mean and
      minimum values of vulnerability indexes was found.

PMID- 17552886
TI  - P-wave body surface isointegral maps in children and in young adults.
AB  - Only limited data are available on body surface potential distribution during
      atrial activation. The aim of this study was to establish the distributions and
      to analyze chosen quantitative parameters of atrial isointegral maps recorded
      using a limited 24-lead system in a young healthy population. A total of 166
      subjects underwent a procedure of body surface potential mapping. Isointegral
      maps during the P wave were constructed and qualitatively and quantitatively
      evaluated. Three types of atrial activation in individual maps were found
      according to the different shape of the zero isointegral line and to mutual
      positions of extrema. The most frequently occurring type resembled the group mean
      maps and was in good agreement with published data obtained from full lead
      systems. The highest extrema were found in the young men group, while,
      surprisingly, the lowest values in the young women group. All minima and the
      majority of maxima were recorded outside the ranges of standard chest leads. The
      usefulness of the limited lead system to record isointegral P wave maps was shown
      and new data were presented that can be useful in noninvasive evaluation of
      atrial pathologies.

PMID- 17552887
TI  - Models of stents - comparison and applications.
AB  - The aim of this study was to analyze the possibilities of various types of stent
      modeling and to develop some new models. A brief survey of basic properties of
      stents and a list of basic designs of stents is presented. Two approaches to
      stent modeling were identified. Structural mechanics is the theoretical
      background of our analytical model of a spiral stent. The finite element method
      was also used. The measurement equipment for model evaluation was developed.

PMID- 17552888
TI  - Use of 3D geometry modeling of osteochondrosis-like iatrogenic lesions as a
      template for press-and-fit scaffold seeded with mesenchymal stem cells.
AB  - Computed tomography (CT) is an effective diagnostic modality for three
      dimensional imaging of bone structures, including the geometry of their defects.
      The aim of the study was to create and optimize 3D geometrical and real plastic
      models of the distal femoral component of the knee with joint surface defects.
      Input data included CT images of stifle joints in twenty miniature pigs with
      iatrogenic osteochondrosis-like lesions in medial femoral condyle of the left
      knee. The animals were examined eight and sixteen weeks after surgery. Philips MX
      8000 MX and View workstation were used for scanning parallel plane cross section
      slices and Cartesian discrete volume creation. On the average, 100 slices were
      performed in each stifle joint. Slice matrices size was 512 x 512 with slice
      thickness of 1 mm. Pixel (voxel) size in the slice plane was 0.5 mm (with average
      accuracy of +/-0.5 mm and typical volume size 512 x 512 x 100 voxels). Three
      dimensional processing of CT data and 3D geometrical modelling, using interactive
      computer graphic system MediTools formerly developed here, consisted of tissue
      segmentation (raster based method combination and 5 % of manual correction),
      vectorization by the marching-cubes method, smoothing and decimation. Stifle-
      joint CT images of three individuals of different body size (small, medium and
      large) were selected to make the real plastic models of their distal femurs from
      plaster composite using rapid prototyping technology of Zcorporation. Accuracy of
      the modeling was +/- 0.5 mm. The real plastic models of distal femurs can be used
      as a template for developing custom made press and fit scaffold implants seeded
      with mesenchymal stem cells that might be subsequently implanted into iatrogenic
      joint surface defects for articular cartilage-repair enhancement.

PMID- 17552889
TI  - Pyramid projection - validation of a new method of skin defect measurement.
AB  - This paper presents a new method for the determination of the volume, surface
      area and depth of skin defects. The method is based on the description of a
      spatial defect using a pyramid (made, for example, from injection needles), which
      is placed over the defect. The projection of the pyramid on to the defect is
      photographed using a digital camera and subsequently compared with the projection
      of the same pyramid on to a sheet of grid paper. The defect is mathematically
      reconstructed on a computer, and an optimal body shape describing the defect is
      found, using a number of simplifications and assumptions. The method was then
      validated using a plaster mold of a real foot with 19 defects simulating real
      wounds. These plaster wounds were molded using alginate hydrocolloid, and the
      volume, surface area and depth were measured and compared with the results of the
      pyramid projection by means of regression analysis.This method correlates in all
      variables with correlation coefficients higher than 0.9. It can be concluded that
      the projection pyramid method correlates well with the reference mold method and
      can be used with good results for a whole range of variables.

PMID- 17552890
TI  - Temperature dependence of blood surface tension.
AB  - Whole blood surface tension of 15 healthy subjects recorded by the ring method
      was investigated in the temperature range from 20 to 40 degrees C. The surface
      tension omega as a function of temperature t ( degrees C) is described by an
      equation of linear regression as omega(t) = (-0.473 t + 70.105) x 10(-3) N/m.
      Blood serum surface tension in the range from 20 to 40 degrees C is described by
      linear regression equation omega(t) = (-0.368 t + 66.072) x 10(-3) N/m and linear
      regression function of blood sediment surface tension is omega(t) = (-0.423 t +
      67.223) x10(-3) N/m.

PMID- 17552891
TI  - Impedance spectroscopy of bilayer lipid membranes self-assembled on agar support 
      interaction with HDL.
AB  - The electrical properties of the supported lipid bilayer membrane (s-BLM) of egg
      phosphatidylcholine (PC) self-assembled on agar surface were examined. To
      characterize the insulating properties of s-BLMs, electrochemical impedance
      spectroscopy (EIS) was used. The analysis of impedance spectra in terms of an
      equivalent circuit of agar/electrolyte and agar/s-BLM/electrolyte in the
      frequency range of 0.1 Hz-10 kHz was performed. The high-density lipoproteins
      (HDL)/s-BLM interaction in the concentration range from 20 microg/ml to 80
      microg/ml of HDL was investigated. It is evident that treatment of s-BLM with HDL
      resulted in an increase of the lipid film resistance and a decrease of membrane
      capacitance.

PMID- 17552892
TI  - Use of chemical dosimetry for comparison of ultrasound and ionizing radiation
      effects on cavitation.
AB  - A comparison of the effects of ultrasound produced by low- and high-frequency
      ultrasonic apparatuses upon biological systems is one of the basic problems when
      studying ultrasound cavitation effects. One possibility for how to compare these
      effects is the indirect method which uses well-known physical quantities
      characterizing the interaction of ionizing radiation with matter and which also
      converts these quantities to one common physical quantity. The comparison was
      performed with two methods applied to the chemical dosimetry of ionizing
      radiation. The first method employed a two-component dosimeter which is composed
      of 50 % chloroform and 50 % re-distilled water (i.e. Taplin dosimeter). The other
      method used a modified iodide dosimeter prepared from a 0.5 M potassium iodide
      solution. After irradiation or ultrasound exposure, measurable chemical changes
      occurred in both dosimeters. The longer the exposure, the greater the chemical
      changes. These effects are described by the relationship of these changes versus
      the exposure times in both dosimeters. The UZD 21 ultrasonic disintegrator (with
      a frequency of 20 kHz, 50 % power output) was used as a low-frequency ultrasound
      source, and the BTL-07 therapeutic instrument (with a frequency of 1 MHz and
      intensity of 2 W/cm2) was used as a high-frequency cavitation ultrasound source.
      For comparison, a 60 Co gamma source was applied (60 Co, gamma energies of 1.17
      and 1.33 MeV, activity of 14 PBq). Results of this study have demonstrated that
      the sonochemical products are generated during exposure in the exposed samples of
      both dosimeters for all apparatuses used. The amount of these products depends
      linearly upon the exposure time. The resulting cavitation effects were
      recalculated to a gray-equivalent dose (the proposed unit is cavitation gray
      [cavitGy]) based on the sonochemical effects compared to the effects of ionizing
      radiation from the 60 Co source.

PMID- 17552893
TI  - Biomechanical characterization of cartilages by a novel approach of blunt impact
      testing.
AB  - The present article introduces a novel method of characterizing the
      macromechanical cartilage properties based on dynamic testing. The proposed
      approach of instrumented impact testing shows the possibility of more detailed
      investigation of the acting dynamic forces and corresponding deformations within
      the wide range of strain rates and loads, including the unloading part of stress
      strain curves and hysteresis loops. The presented results of the unconfined
      compression testing of both the native joint cartilage tissues and potential
      substitute materials outlined the opportunity to measure the dissipation energy
      and thus to identify the initial mechanical deterioration symptoms and to
      introduce a better definition of material damage. Based on the analysis of
      measured specimen deformation, the intact and pathologically changed cartilage
      tissue can be distinguished and the differences revealed.

PMID- 17552894
TI  - Biochemical and biophysical aspects of collagen nanostructure in the
      extracellular matrix.
AB  - ECM is composed of different collagenous and non-collagenous proteins. Collagen
      nanofibers play a dominant role in maintaining the biological and structural
      integrity of various tissues and organs, including bone, skin, tendon, blood
      vessels, and cartilage. Artificial collagen nanofibers are increasingly
      significant in numerous tissue engineering applications and seem to be ideal
      scaffolds for cell growth and proliferation. The modern tissue engineering task
      is to develop three-dimensional scaffolds of appropriate biological and
      biomechanical properties, at the same time mimicking the natural extracellular
      matrix and promoting tissue regeneration. Furthermore, it should be
      biodegradable, bioresorbable and non-inflammatory, should provide sufficient
      nutrient supply and have appropriate viscoelasticity and strength. Attributed to
      collagen features mentioned above, collagen fibers represent an obvious
      appropriate material for tissue engineering scaffolds. The aim of this minireview
      is, besides encapsulation of the basic biochemical and biophysical properties of
      collagen, to summarize the most promising modern methods and technologies for
      production of collagen nanofibers and scaffolds for artificial tissue
      development.

PMID- 17552895
TI  - Effects of static magnetic field and pulsed electromagnetic field on viability of
      human chondrocytes in vitro.
AB  - Effects of electromagnetic fields (EMFs) on human cell lines were described in
      numerous studies, but still many questions remain unanswered. Our experiment was
      designed with the aim of studying the effects of EMFs on the metabolic activity
      of chondrocytes in vitro. Human chondrocyte in vitro cultures, cultured in medium
      supplemented with 20 % fetal calf serum, were exposed to static magnetic field
      (SMF) (intensity of 0.6 T) and pulsed electromagnetic fields (PEMF) (21.2 MHz
      period of 15 ms, burst duration of 2 ms, amplification 3 dBm (0.1 V) and maximum
      output of 250 W) continually for 72 h. After the exposure, viability was
      determined using the MTT test and compared with a non-exposed control culture. As
      compared to the control sample the exposure to SMF resulted in a statistically
      significant increase (p 0.001) in viability. However, the increase of viability
      after PEMF exposure was not significant. This could be due to the frequency
      dependent effect on human cells. The experiments demonstrated that magnetic
      fields, using the above parameters, have a positive effect on the viability of
      human chondrocytes cultured in vitro.

PMID- 17552896
TI  - Biological effects of noble gases.
AB  - Noble gases are known for their inertness. They do not react chemically with any
      element at normal temperature and pressure. Through that, some of them are known
      to be biologically active by their sedative, hypnotic and analgesic properties.
      Common inhalation anesthetics are characterized by some disadvantages (toxicity,
      decreased cardiac output, etc). Inhalation of xenon introduces anesthesia and has
      none of the above disadvantages, hence xenon seems to be the anesthetic gas of
      the future (with just one disadvantage - its cost). It is known that argon has
      similar anesthetic properties (under hyperbaric conditions), which is much
      cheaper and easily accessible. The question is if this could be used in clinical
      practice, in anesthesia of patients who undergo treatment in the hyperbaric
      chamber. Xenon was found to be organ-protective. Recent animal experiments
      indicated that xenon decreases infarction size after ischemic attack on brain or
      heart. The goal of our study is to check if hyperbaric argon has properties
      similar to those of xenon.

PMID- 17552897
TI  - Viscoelasticity of biological materials - measurement and practical impact on
      biomedicine.
AB  - Mechanical behavior of biological structures under dynamic loading generally
      depends on elastic as well as viscous properties of biological materials. The
      significance of "viscous" parameters in real situations remains to be elucidated.
      Behavior of rheological models consisting of a combination of inertial body and
      two Voigt's bodies were described mathematically with respect to inverse problem
      solution, and behavior in impulse and harmonic loadings was analyzed. Samples of
      walls of porcine and human aorta thoracica in transverse direction and samples of
      human bone (caput femoris, substantia compacta) were measured. Deformation
      responses of human skin in vivo were also measured. Values of elastic moduli of
      porcine aorta walls were in the interval from 10(2)kPa to 10(3) kPa, values of
      viscous coefficients were in the interval from 10(2) Pa.s to 10(3) Pa.s. The
      value of shear stress moduli of human caput femoris, substantia compacta range
      from 52.7 to 161.1 MPa, and viscous coefficients were in the interval from 27.3
      to 98.9 kPa.s. The role of viscous coefficients is significant for relatively
      high loading frequencies - in our materials above 8 Hz in aorta walls and 5 Hz
      for bones. In bones, the viscosity reduced maximum deformation corresponding to
      short rectangular stress.

PMID- 17552898
TI  - In vitro study of reactive oxygen species production during photodynamic therapy
      in ultrasound-pretreated cancer cells.
AB  - Several recent studies bring evidence of cell death enhancement in photodynamic
      compound loaded cells by ultrasonic treatment. There are a number of hypotheses
      suggesting the mechanism of the harmful ultrasonic effect. One of them considers
      a process in the activation of photosensitizers by ultrasonic energy. Because the
      basis of the photodynamic damaging effect on cells consists in the production of
      reactive oxygen species (ROS), we focused our study on whether the ultrasound can
      increase ROS production within cancer cells. Particularly, we studied ROS
      formation in ultrasound pretreated breast adenocarcinoma cells during
      photodynamic therapy in the presence of chloroaluminum phthalocyanine disulfonate
      (ClAlPcS2). Production of ROS was investigated by the molecular probe CM-H2DCFDA.
      Our results show that ClAlPcS2 induces higher ROS production in the ultrasound
      pretreated cell lines at a concentration of 100 microM and light intensity of 2
      mW/cm2. We also observed a dependence of ROS production on photosensitizer
      concentration and light dose. These results demonstrate that the photodynamic
      effect on breast cancer cells can be enhanced by ultrasound pretreatment.

PMID- 17552899
TI  - Mechanical response of porous scaffolds for cartilage engineering.
AB  - Mechanical properties of scaffolds seeded with mesenchymal stem cells used for
      cartilage repair seem to be one of the critical factors in possible joint
      resurfacing. In this paper, the effect of adding hyaluronic acid, hydroxyapatite
      nanoparticles or chitosan nanofibers into the cross-linked collagen I on the
      mechanical response of the lyophilized porous scaffold has been investigated in
      the dry state at 37 oC under tensile loading. Statistical significance of the
      results was evaluated using ANOVA analysis. The results showed that the addition
      of hyaluronic acid significantly (p<<0.05) reduced the tensile elastic modulus
      and enhanced the strength and deformation to failure of the modified cross-linked
      collagen I under the used test conditions. On the other hand, addition of
      hydroxyapatite nanoparticles and chitosan nanofibers, respectively, increased the
      elastic modulus of the modified collagen ten-fold and four-fold, respectively.
      Hydroxyapatite caused significant reduction in the ultimate deformation at break
      while chitosan nanofibers enhanced the ultimate deformation under tensile loading
      substantially (p<<0.05). The ultimate tensile deformation was significantly
      (p<<0.05) increased by addition of the chitosan nanofibers. The enhanced elastic
      modulus of the scaffold was translated into enhanced resistance of the porous
      scaffolds against mechanical load compared to scaffolds based on cross-linked
      neat collagen or collagen with hyaluronic acid with similar porosity. It can be
      concluded that enhancing the rigidity of the compact scaffold material by adding
      rigid chitosan nanofibers can improve the resistance of the porous scaffolds
      against compressive loading, which can provide more structural protection to the
      seeded mesenchymal stem cells when the construct is implanted into a lesion.
      Moreover, scaffolds with chitosan nanofibers seemed to enhance cell growth
      compared to the neat collagen I when tested in vitro as well as the scaffold
      stability, extending its resorption to more than 10 weeks.

PMID- 17552900
TI  - Composite hyaluronate-type I collagen-fibrin scaffold in the therapy of
      osteochondral defects in miniature pigs.
AB  - The potential of novel scaffold containing sodium hyaluronate, type I collagen,
      and fibrin was investigated in the regeneration of osteochondral defects in
      miniature pigs. Both autologous chondrocyte-seeded scaffolds and non-seeded
      scaffolds were implanted into two defects located in the non-weight-bearing zone
      of the femoral trochlea (defect A was located more distally and medially, defect
      B was located more proximally and laterally). Control defects were left
      untreated. Twelve weeks after the operation, the knees were evaluated in vivo
      using MRI. Six months after the implantation, the defects were analyzed using
      MRI, histological, and immunohistochemical analysis. In the A defects of
      chondrocyte-seeded scaffold group, hyaline cartilage and fibrocartilage was
      formed, containing type II collagen, acidic and neutral glycosaminoglycans while
      the non-seeded scaffold group was predominantly filled with fibrocartilage.
      Defects in the control group were predominantly filled with fibrous tissue.
      Histomorphometric analysis of photomicrographs revealed a significantly higher
      amount of hyaline cartilage in the cell-seeded scaffold group in A defects than
      in other groups. Both scaffold groups in A defects showed significantly less
      fibrous tissue than cell-seeded defects B and the control group. Both
      histological and MRI analysis proved that the novel composite scaffold has a
      potential to regenerate osteochondral defects within six months.

PMID- 17552901
TI  - Biological effects of two successive shock waves focused on liver tissues and
      melanoma cells.
AB  - A new generator of two successive shock waves focused to a common focal point has
      been developed. Cylindrical pressure waves created by multichannel electrical
      discharges on two cylindrical composite anodes are focused by a metallic
      parabolic reflector - cathode, and near the focus they are transformed to strong
      shock waves. Schlieren photos of the focal region have demonstrated that mutual
      interaction of the two waves results in generation of a large number of secondary
      short-wavelength shocks. Interaction of the focused shockwaves with liver tissues
      and cancer cell suspensions was investigated. Localized injury of rabbit liver
      induced by the shock waves was demonstrated by magnetic resonance imaging.
      Histological analysis of liver samples taken from the injured region revealed
      that the transition between the injured and the healthy tissues is sharp.
      Suspension of melanoma B16 cells was exposed and the number of the surviving
      cells rapidly decreased with increasing number of shocks and only 8 % of cells
      survived 350 shocks. Photographs of cells demonstrate that even small number of
      shocks results in perforation of cell membranes.

PMID- 17552902
TI  - Lysosomal cysteine cathepsins: signaling pathways in apoptosis.
AB  - Apoptosis is the major mechanism by which eukaryotic organisms eliminate
      potentially dangerous, superfluous and damaged cells. Initially, nuclei and
      mitochondria were found to be the key organelles involved in the process.
      However, recent data suggest that lysosomes and the endoplasmic reticulum also
      play important roles in the process. A number of different stimuli were found to
      directly or indirectly target the lysosomal membrane, thereby inducing lysosomal
      permeabilization and the release of cysteine cathepsins and the aspartic protease
      cathepsin D into the cytosol. Once in the cytosol, cathepsins can trigger cell
      death by different mechanisms. Here we discuss the different signaling pathways
      used by lysosomal proteases to trigger apoptosis and their potential role in
      physiological processes.

PMID- 17552903
TI  - Anti-innexin 2 aptamers specifically inhibit the heterologous interaction of the
      innexin 2 and innexin 3 carboxyl-termini in vitro.
AB  - We recently demonstrated that heteromerization of innexins 2 and 3 from
      Drosophila melanogaster (Dm) is crucial for epithelial organization and polarity
      of the embryonic epidermis. Both innexins are thought to interact via their C
      terminal cytoplasmic domains during the assembly of heteromeric gap junction
      channels. However, the mechanisms that control heteromeric versus homomeric
      channel formation are still largely unknown. Here we report the isolation of both
      non-modified and 2'-fluoro-2'-deoxy-modified RNA anti-innexin 2 aptamers by in
      vitro selection. The aptamers bind to a proximal epitope on the carboxyl-tail of
      Dm innexin 2 protein and specifically inhibit the heterologous interaction of
      innexin 2 and innexin 3 carboxyl-termini in vitro. These domain-specific
      inhibitors represent the first step towards functional studies focusing on the
      activity of these domains in vivo.

PMID- 17552905
TI  - Irradiation of GAPDH: a model for environmentally induced protein damage.
AB  - Environmental factors, including sunlight, are able to induce severe oxidative
      protein damage. The modified proteins are either repaired, degraded or escape
      from degradation and aggregate. In the present study we tested the effect of
      different sunlight components such as UV-A, UV-B, and infrared radiation on
      protein oxidation in vitro. We chose glyceraldehyde-3-phosphate dehydrogenase
      (GAPDH) as a model enzyme and analyzed the irradiation-induced enzyme activity
      loss, fragmentation and aggregation, and quantified various oxidative amino acid
      modifications. Since gamma-irradiation was used in numerous studies before, we
      used it for comparative purposes. Infrared radiation was unable to damage GAPDH
      in the dose range tested (0-1000 J/cm(2)). UV-A led to a decrease in free thiol
      content, which was connected with a loss in enzyme activity, while only at very
      high doses could moderate protein aggregation and fragmentation be observed. UV-B
      (0-2 J/cm(2)) and gamma-irradiation (0-500 Gy) led to a dose-dependent increase
      in protein modification. Interestingly, UV-B acted on specific amino acids, such
      as arginine, proline, and tyrosine, whereas gamma-irradiation acted more
      randomly. The possibility of using the amino acid oxidation pattern as a
      biomarker of the source of damage is discussed.

PMID- 17552904
TI  - Characterization of rat BLOS2/Ceap, a putative yeast She3 homolog, as interaction
      partner of apoptosis antagonizing transcription factor/Che-1.
AB  - AATF/Che-1 is a coactivator of several transcription factors, including steroid
      hormone receptors. In search of novel interaction partners of AATF, we identified
      BLOS2 (BLOC1S2, also termed Ceap) from a rat cDNA library. BLOS2 is extremely
      conserved with a high degree of homology to yeast She3p. The clone isolated
      represents a splice variant encoding a polypeptide of 168 residues. Rat BLOS2
      mRNA is highly expressed in brain and testis and at lower levels in other
      tissues, but not in skeletal or smooth muscle. Expression as a tagged fusion
      protein revealed predominant cytoplasmic, but also nuclear localization. In the
      cytoplasm, BLOS2 fusion proteins exhibit diffuse, filamentous, or dotted
      distribution, with the latter partially co-localizing with recycling endosomes.
      In addition, BLOS2 localizes to centrosomes or the pericentrosomal region.
      Moreover, BLOS2 co-localizes with myosin V globular tail domains in vesicle-like
      structures. However, a direct interaction could not be demonstrated. In
      transactivation assays, BLOS2 enhanced transcription from androgen receptor and
      p53-responsive promoters. However, this enhancement correlated with accumulation
      of both androgen receptor and p53, suggesting that BLOS2 has a stabilizing effect
      on these transcription factors. We propose that BLOS2 functions as an adapter in
      processes such as protein and vesicle processing and transport, and perhaps
      transcription.

PMID- 17552906
TI  - Characterisation of two calmodulin-like proteins from the liver fluke, Fasciola
      hepatica.
AB  - Calmodulin is a calcium ion-sensing signalling protein found in eukaryotics. Two
      calmodulin-like gene sequences were identified in an EST library from adult liver
      flukes. One codes for a protein (FhCaM1) homologous to mammalian calmodulins (98%
      identity), whereas the other protein (FhCaM2) has only 41% identity. These genes
      were cloned into expression vectors and the recombinant proteins were expressed
      in Escherichia coli. Gel shift assays showed that both proteins bind to calcium,
      magnesium and zinc ions. Homology models have been built for both proteins. As
      expected, FhCaM1 has a highly similar structure to other calmodulins. Although
      FhCaM2 has a similar fold, its surface charge is higher than FhCaM1. One of the
      potential metal ion-binding sites has lower metal-ion co-ordination capability,
      while another has an adjacent lysine residue, both of which may decrease the
      metal-binding affinity. These differences may reflect a specialised role for
      FhCaM2 in the liver fluke.

PMID- 17552907
TI  - Annexin B1 from Taenia solium metacestodes is a newly characterized member of the
      annexin family.
AB  - We previously reported cloning of the Taenia solium annexin B1 gene from a
      metacestode cDNA expression library and demonstrated that it acts as a protective
      antigen for effective vaccine development against cysticercosis. In the present
      study we produced recombinant annexin B1 and antiserum against the protein to
      investigate its structural and functional properties. Western blotting of
      metacestode fractions indicated that T. solium annexin B1, similar to vertebrate
      annexins, associates with acid phospholipids in the presence of Ca(2+). This
      property was confirmed by the recognition of apoptotic cells by labeled annexin
      B1. CD spectroscopy results demonstrated that alpha-helices are the main
      secondary structures of the protein. Ca(2+) binding increases the alpha-helix
      content and causes significant thermal stabilization with a melting temperature
      increase of approximately 10 degrees C. Functional Ca(2+)-dependent phospholipid
      binding sites of annexin B1 were investigated using mutant proteins. By changing
      a conserved acidic amino acid residue that putatively combines Ca(2+) in each
      domain of annexin B1 singly or in combination, we found that Ca(2+) binding in
      the first domain is more important than that at the other Ca(2+) binding sites.
      Annexin B1 is a metacestode stage-specific antigen, with the protein being mainly
      localized in the teguments and surrounding cyst wall of T. solium metacestodes,
      suggesting a role in the parasite-host interaction.

PMID- 17552908
TI  - Competitive displacement of full-length HIV-1 Nef from the Hck SH3 domain by a
      high-affinity artificial peptide.
AB  - We studied the interaction of the artificial 12-aa proline-rich peptide PD1 with
      the SH3 domain of the hematopoietic cell kinase Hck and the peptide's potency in
      competitively displacing HIV-1 Nef from the Hck SH3 domain. PD1 was obtained from
      a phage display screen and exhibits exceptional affinity for the Hck SH3 domain
      (K(d)=0.23 microM). Competition experiments using NMR spectroscopy demonstrate
      that the peptide even displaces Nef from Hck SH3 and allow for estimation of the
      Nef-Hck SH3 dissociation constant (K(d)=0.44 microM), the strongest SH3 ligand
      interaction known so far. Consequences of this study for novel antiviral concepts
      are discussed.

PMID- 17552909
TI  - Development of an assay for the intermembrane transfer of cholesterol by Niemann
      Pick C2 protein.
AB  - Niemann-Pick type C disease is an inherited fatal disorder characterized by the
      accumulation of unesterified cholesterol and other lipids in the
      endosomal/lysosomal compartment. Two independent genes responsible for this
      neurodegenerative disorder have been identified, but the precise functions of the
      encoded Niemann-Pick C1 (NPC1) and C2 (NPC2) proteins are not yet known. We
      developed a cell-free assay for measuring intermembrane lipid transport and
      examined the ability of bovine NPC2 (bNPC2) for intermembrane cholesterol
      transfer. NPC2 specifically extracts cholesterol from phospholipid bilayers and
      catalyzes intermembrane transfer to acceptor vesicles in a dose- and time
      dependent manner. This transfer activity is dependent on temperature, pH, ionic
      strength, lipid composition of the model membranes, and the ratio of donor to
      acceptor vesicles. In model membranes, the presence of the lysosomal anionic
      phospholipids bis(monooleoylglycero)phosphate and phosphatidyl inositol
      significantly stimulated cholesterol transfer by NPC2, whereas
      bis(monomyristoylglycero)phosphate, phosphatidyl serine, and phosphatidic acid
      had no effect. Moreover, ceramide stimulated cholesterol transfer slightly,
      whereas sphingomyelin reduced cholesterol transfer rates. With our assay system
      we identified for the first time the ability of other lysosomal proteins, most
      notably the GM2-activator protein, to mediate intermembrane cholesterol transfer.
      This assay system promises to be a valuable tool for further quantitative and
      mechanistic studies of protein-mediated lipid transfer.

PMID- 17552910
TI  - Inhibition of inducible tumor necrosis factor-alpha expression by the fungal
      epipolythiodiketopiperazine gliovirin.
AB  - TNF-alpha is a major pro-inflammatory cytokine that regulates further cytokine
      induction, especially of IL-1 and IL-6, in many human diseases including cancer,
      inflammation and immune disorders. In a search for new inhibitors of inducible
      TNF-alpha promoter activity and expression, cultures of the imperfect fungus
      Trichoderma harzianum were found to produce gliovirin, a previously isolated
      epipolythiodiketopiperazine. Gliovirin inhibited inducible TNF-alpha promoter
      activity and synthesis in LPS/IFN-gamma-stimulated macrophages/monocytes and
      Jurkat T-cells, co-stimulated with 12-O-tetradecanoylphorbol-13-acetate
      (TPA)/ionomycin, in a dose-dependent manner, with IC(50) values ranging from 0.21
      to 2.1 microM (0.1-1 microg/ml). Studies on the mode of action revealed that
      gliovirin suppresses TNF-alpha synthesis by inhibiting the activation of
      extracellular signal-regulated kinase (ERK), thereby blocking the pathway leading
      to activation of the transcription factors AP-1 and NF-kappaB, the latter of
      which is involved in the inducible expression of many pro-inflammatory genes.
      Gliovirin also significantly reduced TPA/ionomycin-induced IL-2 mRNA levels and
      synthesis in Jurkat cells at low micromolar concentrations.

PMID- 17552911
TI  - Increased carcinogenic potential of myeloid tumor cells induced by aberrant TGF
      beta1-signaling and upregulation of cathepsin B.
AB  - The TGF-beta signaling pathways are implicated in cancer. Cysteine cathepsins can
      contribute to the carcinogenic potential of tumor cells. The aim of this study
      was to investigate the regulation of cysteine cathepsin expression by TGF-beta1
      and the functional implications in tumor cells. We found an upregulation of
      cathepsin B (CathB, 2- to 5-fold) in different myeloid tumor cells (THP-1,
      MonoMac-1, MonoMac-6) after incubation with TGF-beta1. No upregulation was found
      in monocytes, and there was suppression of CathB expression in epithelial tumor
      cells (A549). Increased cathepsin B activity led to enhanced carcinogenic
      potential, which was reflected by increased migration and invasion of the cells
      and resistance to inhibitor-induced apoptosis. Analysis of the TGF-beta signaling
      pathways showed no alterations in TGF-beta/BMP receptor expression or SMAD2/3
      phosphorylation, and no influence of MAP kinase pathways. However, a reduction in
      SMAD1 expression was detected. The lack of BMP action on cysteine cathepsin
      expression in myeloid tumor cells, but not in epithelial tumor cells, suggests a
      defect in the Smad1/Smad5 pathway. We located a related TGF-beta1-responsive
      element within the first intron of the CathB gene. In conclusion, alterations in
      the TGF-beta1 signaling pathway lead to upregulation of CathB, which contributes
      to the carcinogenic potential of tumor cells.

PMID- 17552912
TI  - Selection of vimentin-specific antibodies from the HuCAL phage display library by
      subtractive panning on formalin-fixed, paraffin-embedded tissue.
AB  - We describe the direct isolation of specific antibodies on formalin-fixed,
      paraffin-embedded (FFPE) tissue. The technique involves subtractive selection of
      a large and highly diverse combinatorial human antibody phage library (HuCAL) on
      lymphocyte FFPE tissue sections. Tissue sections from normal human tonsil tissue
      were used to deplete the library of binders to most housekeeping proteins. Mantle
      cell lymphoma tissue was used for positive selection and enrichment of mantle
      cell or tumor-specific antibody phage. We established a high-throughput
      immunohistochemical method for screening of antibody clones selected from FFPE
      tissue. One recombinant antibody showed specific staining for interfollicular and
      mantle cells in FFPE tissue. Immunoprecipitation with this antibody and
      subsequent mass spectrometric analysis revealed specificity for vimentin.

PMID- 17552913
TI  - Proteomic analysis of saliva for cancer diagnosis.

PMID- 17552914
TI  - Proteomics and the human metabolome project.

PMID- 17552916
TI  - Neuroproteomics: the hunt for biomarkers of neurotrauma. Andrew Ottens talks to
      Nicole Nogoy.

PMID- 17552917
TI  - Advances in proteomics in cancer research.

PMID- 17552918
TI  - Computational prediction of proteotypic peptides.

PMID- 17552919
TI  - Discontinuous native protein gel electrophoresis: pros and cons.
AB  - A new native protein gel system was recently developed that enables the rapid and
      convenient analysis of virtually all soluble proteins, in particular including
      basic proteins, in their native oligomeric states. This gel system combines the
      addition of negative charges to the proteins by the dye SERVA Blue G with a Tris
      histidine discontinuous buffer system and the use of polyacrylamide gradient
      gels. The use of histidine for sample focusing rather than glycine as a slow
      dipolar ion following from the cathode buffer serves to improve migration of
      basic proteins. In this review, the principle of function as well as the
      advantages and disadvantages of the new gel system are discussed in the context
      of other native protein gel systems and further methods for the analysis of the
      oligomeric state of a protein.

PMID- 17552920
TI  - Plasma/serum proteomics: pre-analytical issues.
AB  - High-throughput proteomics technologies tend to provide highly sensitive
      information about living tissues and biological fluids. Analytes are
      characterized by intrinsic and extrinsic properties, the latter depending on each
      phase of their preparation, sometimes adding artifacts with crucial repercussions
      in result reliability and interpretation. This review aims to address some issues
      that can be encountered when handling plasma and serum in experimental and
      clinical proteomic settings.

PMID- 17552921
TI  - Proteomic analysis of bone cancer: a review of current and future developments.
AB  - The ability of sophisticated proteomic approaches to scrutinize the dynamic
      nature of protein expression, cellular and subcellular protein distribution, post
      translational modifications, and protein-protein interactions has culminated in
      the identification of many potential new therapeutic targets and an abundance of
      cancer-related biomarkers. From a proteomics perspective, amongst the most under
      studied diseases are bone cancers, such as myeloma, osteosarcoma and breast and
      prostate cancer bony metastases. This review focuses on the recent advances in
      proteomic technology that have thrust the skeletal cancer field into this
      exciting age of proteomics, and highlights the future work that is required to
      adapt this technology to specifically interrogate the skeletal consequences of
      malignancy.

PMID- 17552922
TI  - Role of proteomics in the investigation of pulmonary fibrosis.
AB  - Pulmonary fibrosis arises as a consequence of aberrant remodeling and defective
      repair mechanisms within the lung. This destructive process is the cause of much
      of the morbidity and mortality in many pulmonary disorders. Unfortunately,
      therapeutic options are limited. A significant advancement in the management of
      patients with pulmonary fibrosis would be the identification of biomarkers for
      diagnosis, prognosis and prediction of patient response to therapy.
      Bronchoalveolar lavage is an ideal tissue target for the discovery of these
      potential biomarkers in pulmonary fibrosis. Integrative approaches using both gel
      and mass spectrometry-based proteomic workflows will allow full coverage of this
      complex proteome, thereby unlocking this potential information as a clinical tool
      to aid diagnosis and guide treatment for individual patients with pulmonary
      fibrosis.

PMID- 17552923
TI  - NMR-based metabolomics approach to target biomarkers for human prostate cancer.
AB  - In the era of genomics and proteomics, metabolomics offers a unique way to probe
      the underlying biochemistry of malignant transformations. In the context of
      oncological metabolomics, the study of the global variation of metabolites
      involved in the development and progression of cancers, few existing techniques
      offer as much potential to discover biomarkers as nuclear magnetic resonance
      techniques. The most fundamental magnetic resonance methodologies with regard to
      human prostate cancer are magnetic resonance spectroscopy and magnetic resonance
      spectroscopic imaging. Recent in vivo explorations have examined crucial
      metabolites that may indicate cancerous lesions and have the potential to direct
      treatment; while ex vivo studies of prostatic fluids and tissues have defined
      novel diagnostic parameters and indicated that magnetic resonance methodologies
      will be paramount in future prostate cancer management.

PMID- 17552924
TI  - Oncoproteomics: current trends and future perspectives.
AB  - Oncoproteomics is the application of proteomics technologies in oncology.
      Functional proteomics is a promising technique for the rational identification of
      biomarkers and novel therapeutic targets for cancers. Recent progress in
      proteomics has opened new avenues for tumor-associated biomarker discovery. With
      the advent of new and improved proteomics technologies, such as the development
      of quantitative proteomic methods, high-resolution, -speed and -sensitivity mass
      spectrometry and protein arrays, as well as advanced bioinformatics for data
      handling and interpretation, it is now possible to discover biomarkers that can
      reliably and accurately predict outcomes during cancer management and treatment.
      However, there are several difficulties in the study of proteins/peptides that
      are not inherent in the study of nucleic acids. New challenges arise in large
      scale proteomic profiling when dealing with complex biological mixtures.
      Nevertheless, oncoproteomics offers great promise for unveiling the complex
      molecular events of tumorigenesis, as well as those that control clinically
      important tumor behaviors, such as metastasis, invasion and resistance to
      therapy. In this review, the development and advancement of oncoproteomics
      technologies for cancer research in recent years are expounded.

PMID- 17552925
TI  - Chemogenomics approaches to novel target discovery.
AB  - Chemogenomics involves the combination of a compound's effect on biological
      targets together with modern genomics technologies. The merger of these two
      methodologies is creating a new way to screen for compound-target interactions,
      as well as map chemical and biological space in a parallel fashion. The challenge
      associated with mining complex databases has initiated the development of many
      novel in silico tools to profile and analyze data in a systematic way. The
      ability to analyze the combinatorial effects of chemical libraries on biological
      systems will aid the discovery of new therapeutic entities. Chemogenomics
      provides a tool for the rapid validation of novel targeted therapeutics, where a
      specific molecular target is modulated by a small molecule. Along with targeted
      therapies comes the ability to discovery pathway nodes where a single molecular
      target might be an essential component of more than one disease. Several disease
      areas will benefit directly from the chemogenomics approach, the most advanced
      being cancer. A genetic loss-of-function screen can be modulated in the presence
      of a compound to search for genes or pathways involved in the compound's
      activity. Several recent papers highlight how chemogenomics is changing with RNA
      interference-based screening and shaping the discovery of new targeted therapies.
      Together, chemical and RNA interference-based screens open the door for a new way
      to discovery disease-associated genes and novel targeted therapies.

PMID- 17552926
TI  - Quantitation of target proteins and post-translational modifications in affinity
      based proteomics approaches.
AB  - As proteomics attempts to enter clinical and diagnostic application, key issues
      surrounding the viability of various proteomics approaches must be evaluated. A
      major issue at the forefront of discussion is the ability to quantitate protein
      targets, including the discrimination of endogenous variants that are the result
      of genetic and post-translational modifications. Mass spectrometry is the logical
      solution to this problem because of its ability to capitalize on the intrinsic
      property of molecular mass. However, the ability to successfully compete with
      classical immunoassays, the dominant technologies in the clinical and diagnostic
      world for quantitative protein assessment, is not a trivial task. This review
      offers a comprehensive discussion regarding some of the major developments in
      quantitative approaches towards both top-down and bottom-up proteomics. Described
      in more detail is the mass spectrometric immunoassay, including examples of how
      immunoaffinity capture is enhanced with mass spectrometry detection, and the use
      of this approach in protein quantification may be viewed as an improvement of the
      currently accepted clinical and diagnostic methodologies.

PMID- 17552930
TI  - Visual category-selectivity for faces, places and objects emerges along different
      developmental trajectories.
AB  - The organization of category-selective regions in ventral visual cortex is well
      characterized in human adults. We investigated a crucial, previously unaddressed,
      question about how this organization emerges developmentally. We contrasted the
      developmental trajectories for face-, object-, and place-selective activation in
      the ventral visual cortex in children, adolescents, and adults. Although children
      demonstrated adult-like organization in object- and place-related cortex, as a
      group they failed to show consistent face-selective activation in classical face
      regions. The lack of a consistent neural signature for faces was attributable to
      (1) reduced face-selectivity and extent of activation within the regions that
      will become the FFA, OFA, and STS in adults, and (2) smaller volumes and
      considerable variability in the locus of face-selective activation in individual
      children. In contrast, adolescents showed an adult-like pattern of face-selective
      activation, although it was more right-lateralized. These findings reveal
      critical age-related differences in the emergence of category-specific functional
      organization in the visual cortex and support a model of brain development in
      which specialization emerges from interactions between experience-dependent
      learning and the maturing brain.

PMID- 17552931
TI  - Enculturated chimpanzees imitate rationally.
AB  - Human infants imitate others' actions 'rationally': they copy a demonstrator's
      action when that action is freely chosen, but less when it is forced by some
      constraint (Gergely, Bekkering & Kiraly, 2002). We investigated whether
      enculturated chimpanzees (Pan troglodytes) also imitate rationally. Using Gergely
      and colleagues' (2002) basic procedure, a human demonstrator operated each of six
      apparatuses using an unusual body part (he pressed it with his forehead or foot,
      or sat on it). In the Hands Free condition he used this unusual means even though
      his hands were free, suggesting a free choice. In the Hands Occupied condition he
      used the unusual means only because his hands were occupied, suggesting a
      constrained or forced choice. Like human infants, chimpanzees imitated the
      modeled action more often in the Hands Free than in the Hands Occupied condition.
      Enculturated chimpanzees thus have some understanding of the rationality of
      others' intentional actions, and use this understanding when imitating others.

PMID- 17552932
TI  - Individuation of pairs of objects in infancy.
AB  - Looking-time studies examined whether 11-month-old infants can individuate two
      pairs of objects using only shape information. In order to test individuation,
      the object pairs were presented sequentially. Infants were familiarized either
      with the sequential pairs, disk-triangle/disk-triangle (XY/XY), whose shapes
      differed within but not across pairs, or with the sequential pairs, disk
      disk/triangle-triangle (XX/YY), whose shapes differed across but not within
      pairs. The XY/XY presentation looked to adults like a single pair of objects
      presented repeatedly, whereas the XX/YY presentation looked like different pairs
      of objects. Following familiarization to these displays, infants were given a
      series of test trials in which the screen was removed, revealing two pairs of
      objects in one of two outcomes, XYXY or XXYY. On the first test trial, infants
      familiarized with the identical pairs (XY/XY) apparently expected a single pair
      to be revealed because they looked longer than infants familiarized with the
      distinct pairs (XX/YY). Infants who had seen the distinct pairs apparently
      expected a double pair outcome. A second experiment showed outcomes of a single
      XY pair. This outcome is unexpected for XX/YY-familiarized infants but expected
      for XY/XY-familiarized infants, the reverse of Experiment 1. This time looking
      times were longer for XX/YY infants. Eleven-month-olds appear to be able to
      represent not just individual objects but also pairs of objects. These results
      suggest that if they can group the objects into sets, infants may be able to
      track more objects than their numerosity limit or available working memory slots
      would normally allow. We suggest possible small exact numerosity representations
      that would allow tracking of such sets.

PMID- 17552933
TI  - Heterogeneity impairs numerical matching but not numerical ordering in preschool
      children.
AB  - Do preschool children appreciate numerical value as an abstract property of a set
      of objects? We tested the influence of stimulus features such as size, shape, and
      color on preschool children's developing nonverbal numerical abilities. Children
      between 3 and 5 years of age were tested on their ability to estimate number when
      the sizes, shapes, and colors of the elements in an array were varied
      (heterogeneous condition) versus when they did not vary (homogeneous condition).
      One group of children was tested on an ordinal task in which the goal was to
      select the smaller of two arrays while another group of children was tested on a
      match-to-sample task in which the goal was to choose one of two visual arrays
      that matched the sample in number. Children performed above chance on both
      homogeneous and heterogeneous stimuli in both tasks. However, while children
      showed no impairment on heterogeneous relative to homogeneous arrays in the
      ordering task, performance was impaired by heterogeneity in the matching task. We
      suggest that nonverbal numerical abstraction occurs early in development, but
      specific task objectives may prevent children from engaging in numerical
      abstraction.

PMID- 17552934
TI  - Neural correlates of mapping from phonology to orthography in children performing
      an auditory spelling task.
AB  - Age-related differences (9- to 15-year-olds) in the neural correlates of mapping
      from phonology to orthography were examined with functional magnetic resonance
      imaging (fMRI). Participants were asked to determine if two spoken words had the
      same spelling for the rime (corresponding letters after the first consonant or
      consonant cluster). Some of the word pairs had conflicting orthography and
      phonology (e.g. jazz-has, pint-mint) whereas other pairs had non-conflicting
      information (e.g. press-list, gate-hate) (see Table 1). There were age-related
      increases in activation for lexical processing (across conflicting and non
      conflicting conditions) in left inferior parietal lobule, suggesting that older
      children have a more elaborated system for mapping between phonology and
      orthography that includes connections at different grain sizes (e.g. phonemes,
      onset-rimes, syllables). In addition, we found that the conflicting conditions
      had lower accuracy, slower reaction time and greater activation in left inferior
      frontal gyrus as compared to non-conflicting conditions. Higher accuracy was also
      correlated with greater activation in left inferior frontal gyrus for the most
      difficult conflicting condition (e.g. jazz-has). The finding of both a conflict
      effect and a correlation with accuracy in left inferior frontal gyrus suggests
      that this region may be involved in resolving the conflict between orthographic
      and phonological representations.

PMID- 17552935
TI  - Evidence of a shift from featural to configural face processing in infancy.
AB  - Two experiments examined whether 4-, 6-, and 10-month-old infants process natural
      looking faces by feature, i.e. processing internal facial features independently
      of the facial context or holistically by processing the features in conjunction
      with the facial context. Infants were habituated to two faces and looking time
      was measured. After habituation they were tested with a habituation face, a
      switch-face, or a novel face. In the switch-faces, the eyes and mouth of the
      habituation faces were switched. The results showed that the 4-month-olds
      processed eyes and mouth by feature, whereas the 10-month-olds processed both
      features holistically. The 6-month-olds were in a transitional stage where they
      processed the mouth holistically but the eyes still as a feature. Thus, the
      results demonstrated a shift from featural to holistic processing in the age
      range of 4 to 10 months.

PMID- 17552936
TI  - Socioeconomic gradients predict individual differences in neurocognitive
      abilities.
AB  - Socioeconomic status (SES) is associated with childhood cognitive achievement. In
      previous research we found that this association shows neural specificity;
      specifically we found that groups of low and middle SES children differed
      disproportionately in perisylvian/language and prefrontal/executive abilities
      relative to other neurocognitive abilities. Here we address several new
      questions: To what extent does this disparity between groups reflect a gradient
      of SES-related individual differences in neurocognitive development, as opposed
      to a more categorical difference? What other neurocognitive systems differ across
      individuals as a function of SES? Does linguistic ability mediate SES differences
      in other systems? And how do specific prefrontal/executive subsystems vary with
      SES? One hundred and fifty healthy, socioeconomically diverse first-graders were
      administered tasks tapping language, visuospatial skills, memory, working memory,
      cognitive control, and reward processing. SES explained over 30% of the variance
      in language, and a smaller but highly significant portion of the variance in most
      other systems. Statistically mediating factors and possible interventional
      approaches are discussed.

PMID- 17552937
TI  - Social transmission of disinhibition in young children.
AB  - The present study examined whether young children's behaviors in the Dimensional
      Change Card Sorting task can be influenced by their observation of another person
      performing the task. Experiment 1 showed that after children watched an adult
      sorting cards according to one rule, although the children were instructed to
      sort the cards according to a new rule, most 3-year-olds made perseverative
      errors and used the observed, old rule to sort the cards instead of the new rule.
      However, only some 4-year-olds and few 5-year-olds made the same mistake.
      Experiments 2, 3 and 4 showed that the younger children took into consideration
      social pragmatic information displayed by the adult model when deciding to use
      the old rule or the new rule. When the model appeared to know that she sorted the
      cards incorrectly (Experiments 2 and 3), or was uncertain whether she sorted
      cards correctly (Experiment 4), most 3-year-olds no longer committed
      perseverative errors. When the adult model was confident about her sorting or
      oblivious to her sorting errors, most 3-year-olds made perseverative errors.
      These results taken together suggest that social observation can lead to
      disinhibitions. In other words, disinhibition can be transmitted socially from
      one person to another.

PMID- 17552938
TI  - The role of kinetic information in newborns' perception of illusory contours.
AB  - Previous research, in which static figures were used, showed that the ability to
      perceive illusory contours emerges around 7 months of age. However, recently,
      evidence has suggested that 2-3-month-old infants are able to perceive illusory
      contours when motion information is available (Johnson & Mason, 2002; Otsuka &
      Yamaguchi, 2003). The present study was aimed at investigating whether even
      newborns might perceive kinetic illusory contours when a motion easily detected
      by the immature newborn's visual system (i.e. stroboscopic motion) is used. In
      Experiment 1, using a preference looking technique, newborns' perception of
      kinetic illusory contours was explored using a Kanizsa figure in a static and in
      a kinetic display. The results showed that newborns manifest a preference for the
      illusory contours only in the kinetic, but not in the static, condition. In
      Experiment 2, using an habituation technique, newborns were habituated to a
      moving shape that was matched with the background in terms of random-texture
      surface; thus the recovery of the shape was possible relying only on kinetic
      information. The results showed that infants manifested a novelty preference when
      presented with luminance-defined familiar and novel shapes. Altogether these
      findings provide evidence that motion enhances (Experiment 1) and sometimes is
      sufficient (Experiment 2) to induce newborns' perception of illusory contours.

PMID- 17552939
TI  - The development of prudence in the face of varying future rewards.
AB  - The choice to delay gratification, opting for a greater reward later instead of a
      smaller reward now, has been used as a measure of preschoolers' ability to make
      future-oriented decisions. The present studies investigated to what extent these
      choice tasks reflect children's ability to make choices in favour of their future
      self. In Experiment 1, preschoolers were presented with choices between a smaller
      immediate reward of one sticker and larger delayed rewards varying in amount from
      two to five stickers. Whereas 3-year-olds showed no increased tendency to choose
      the delayed option as quantity increased from two to five, 4-year-olds' future
      oriented choices reflected the value of the delayed reward. In Experiment 2,
      preschoolers chose between immediate and delayed rewards that were equal in
      amount and varied between one and four stickers. Three-year-olds reliably chose
      the immediate reward and showed no differentiation among rewards, whereas 4-year
      olds chose in a manner that suggested they were trying to satisfy both immediate
      and future desires. Together these results support the notion that future
      oriented prudence reflects growth in concern for the future self.

PMID- 17552940
TI  - Developmental biology and genetics of dental malformations.
AB  - The synthesis of tooth development biology with human studies focusing on
      inherited conditions that specifically interfere with tooth development is
      improving our understanding of normal and pathological tooth formation. The type
      of inherited dental malformations observed in a given kindred relate to when,
      during odontogenesis, the defective gene is critically expressed. Information
      about the protein encoded by the defective gene and the resulting dental
      phenotype helps us understand the major processes underway at different stages
      during tooth development. Genes affecting early tooth development (PAX9, MSX1,
      and AXIN2) are associated with familial tooth agenesis or oligodontia. Genes
      expressed by odontoblasts (COL1A1, COL1A2, and DSPP), and ameloblasts (AMELX,
      ENAM, MMP20, and KLK4) during the crown formation stage, are associated with
      dentinogenesis imperfecta, dentin dysplasia, and amelogenesis imperfecta. Late
      genes expressed during root formation (ALPL and DLX3) are associated with
      cementum agenesis (hypophosphatasia) and taurodontism. Understanding the
      relationships between normal tooth development and the dental pathologies
      associated with inherited diseases improves our ability to diagnose and treat
      patients suffering the manifestations of inherited dental disorders.

PMID- 17552941
TI  - Potential role of PC-1 expression and pyrophosphate elaboration in the molecular
      etiology of the FGFR-associated craniosynostosis syndromes.
AB  - BACKGROUND: Fibroblast growth factor/fibroblast growth factor receptor (FGF/FGFR)
      signaling is associated with the aberrant mineralization phenotype of the
      craniosynostosis syndromes. One critical aspect of mineralization involves the
      elaboration and transport of pyrophosphate into the extracellular matrix with
      subsequent enzymatic hydrolysis into phosphate. We have previously shown that
      FGF2 up-regulates expression of the pyrophosphate generating enzyme, PC-1, and
      the pyrophosphate channel, ANK, while down-regulating expression of the
      pyrophosphate hydrolyzing enzyme, tissue non-specific alkaline phosphatase in pre
      osteoblastic, MC3T3E1(C4) cells. These results suggest that FGF/FGFR signaling
      may affect mineralization via changes in the elaboration and metabolism of
      pyrophosphate. OBJECTIVES: We are currently conducting experiments towards a more
      systematic analysis of PC-1 expression in osteoblastic cells, in order to more
      clearly elucidate the significance of pyrophosphate elaboration in the process of
      normal bone mineralization and in the molecular etiology of the FGFR-associated
      craniosynostosis syndromes. DESIGN: Towards this goal we have constructed a PC-1
      gene promoter/firefly luciferase reporter construct, in order to more directly
      investigate the regulation of PC-1 by FGF/FGFR signaling in osteoblastic and non
      osteoblastic cells. RESULTS AND CONCLUSIONS: Preliminary results confirm that
      FGF/FGFR signaling, either via treatment with FGF2 or via expression of a Crouzon
      syndrome-associated mutant FGFR2, induces PC-1 promoter activity in osteoblastic
      cells in culture. This appears to be a cell type specific phenomenon. These
      results suggest that the expression of PC-1 downstream of FGF signaling is an
      integral aspect of osteoblastic function, and that pyrophosphate elaboration may
      play a significant role in the pathology of craniosynostosis.

PMID- 17552942
TI  - FGF signaling in mandibular skeletogenesis.
AB  - OBJECTIVE: To examine the functions of FGF/FGFR signaling during mandibular
      skeletogenesis in ovo. DESIGN: We examined the effects of inhibition of FGF
      signaling during mandibular skeletogenesis by overexpressing replication
      competent RCAS virus encoding a truncated form of FGFR3 in the chicken mandibular
      process between stages 17 and 26. RESULTS: Injection of RCAS-dnFGFR3 into the
      developing mandible resulted in abnormalities in a stage- and region-dependent
      manner. Injection at early stages of development resulted in the truncation of
      Meckel's cartilage, severely reduced outgrowth of the mandibular process and
      absence of five of the mandibular bones. Injection at later stages did not affect
      the outgrowth of the mandibular process and Meckel's cartilage but resulted in
      abnormalities in mandibular osteogenesis in a region-specific manner. The bones
      in the more caudal region were frequently truncated whereas bones in the more
      rostral regions such as dentary and splenial bones were frequently absent.
      CONCLUSION: Together these experiments have revealed essential roles for FGF/FGFR
      signaling in the elongation of Meckel's cartilage, development of osteogenic
      condensations and appositional growth of mandibular bones.

PMID- 17552943
TI  - Syndromic craniosynostosis: from history to hydrogen bonds.
AB  - The syndromic craniosynostoses, usually involving multiple sutures, are
      hereditary forms of craniosynostosis associated with extracranial phenotypes such
      as limb, cardiac, CNS and tracheal malformations. The genetic etiology of
      syndromic craniosynostosis in humans is only partially understood. Syndromic
      synostosis has been found to be associated with mutations of the fibroblast
      growth factor receptor family (FGFR1, -R2, -R3), TWIST1, MSX2, and EFNB1. Apert,
      Pfeiffer, Crouzon, and Jackson-Weiss syndromes are due to gain-of-function
      mutations of FGFR2 in either the Ig II-III linker region (Apert) or Ig III
      domain. Loss of function mutations of TWIST1 and gain-of-function mutations of
      MSX2 lead to Saethre-Chotzen and Boston-type syndromes, respectively. The
      mutations in Pfeiffer (FGFR1), Muenke (FGFR3), and Apert syndrome (FGFR2) are
      caused by the same amino acid substitution in a highly conserved region of the Ig
      II-III linker region of these proteins, which suggests that these receptor
      tyrosine kinases have an overlapping function in suture biology. In this review
      we will discuss the historical descriptions, current phenotypes and molecular
      causes of the more common forms of syndromic craniosynostosis.

PMID- 17552944
TI  - Subclinical features in non-syndromic cleft lip with or without cleft palate
      (CL/P): review of the evidence that subepithelial orbicularis oris muscle defects
      are part of an expanded phenotype for CL/P.
AB  - OBJECTIVES: Non-syndromic cleft lip with or without cleft palate (CL/P) is a
      common, complex birth defect with a wide phenotypic spectrum. This review
      summarizes the evidence that subepithelial (occult) defects of the superior
      orbicularis oris (OO) muscle represent the mildest form of the lip portion of
      CL/P. EXPERIMENTAL DESIGN: The rate of OO defects was assessed via ultrasound in
      non-CL/P relatives of individuals with CL/P and compared with controls.
      Descriptive histology of OO muscles from cadavers was carried out. BMP4 was
      sequenced in non-CL/P individuals with OO defects vs. controls. RESULTS: 1) Non
      CL/P relatives of individuals with overt CL/P have a significantly increased
      frequency of OO defects compared with controls with no family history of CL/P; 2)
      Preliminary histological studies of cadaver OO muscles show a pattern of
      disorganized muscle fibers in an individual with OO discontinuities as seen on
      ultrasound compared with another individual with no OO defect. That is, the
      defects seen on ultrasound appear to have an anatomical basis; 3) Sequencing BMP4
      found a significant increase in potentially damaging mutations in individuals
      with OO defects vs. controls. CONCLUSIONS: Taken together, these data provide
      significant support for the hypothesis that subepithelial OO muscle defects are a
      mild manifestation of the lip portion of the CL/P phenotype. Given that
      subepithelial OO muscle defects are relatively straightforward to identify via
      ultrasound, such defects show great promise for providing more accurate
      recurrence risk estimates to relatives in cleft families. Furthermore, inclusion
      of OO defects in the CL/P phenotypic spectrum should improve the power of genetic
      studies.

PMID- 17552945
TI  - Treacher Collins syndrome.
AB  - Treacher Collins syndrome (TCS) is an autosomal dominant disorder of craniofacial
      development which results from loss-of-function mutations in the gene TCOF1.
      TCOF1 encodes the nucleolar phosphoprotein, Treacle, which plays a key role in
      pre-ribosomal processing and ribosomal biogenesis. In mice, haploinsufficiency of
      Tcof1 results in a depletion of neural crest cell precursors through high levels
      of cell death in the neuroepithelium, which results in a reduced number of neural
      crest cells migrating into the developing craniofacial complex. These combined
      advances have already impacted on clinical practice and provide invaluable
      resources for the continued dissection of the developmental basis of TCS.

PMID- 17552946
TI  - Stigma experiences in youth with facial differences: a multi-site study of
      adolescents and their mothers.
AB  - OBJECTIVES: To describe stigma experiences of adolescents with congenital and
      acquired facial differences. DESIGN: Used baseline cross-sectional stigma-related
      responses from a four site (Seattle WA, Galveston TX, Chicago IL and Chapel Hill
      NC) US study enrolling 185 English speaking, US participants ages 1118 years old
      with facial differences (60% male; 80% congenital conditions). Closed-ended, self
      administered questions drawn from the Youth Quality of Life Instrument Facial
      Differences Module (YQOL-FD) determined perceptions of stigmatization. Mothers
      (n=153) were independently asked seven matching questions. RESULTS: Frequencies
      report combined responses of 'sometimes,' 'fairly often,' and 'very often.'
      Mother's responses are in parentheses. *35% (47%) noticed people staring at their
      face in the past week. * 28% (43%) talked with others about how their face looks
      in the past month. * 29% (31%) heard others say something about their face in the
      past month. * 32% (32%) told peers about their facial difference in the past
      month. * 12% (12%) felt left out of doing things with peers because of how their
      face looks in the past month. * 11% (8%) got into a fight because of how their
      face looks in the past month. * 20% (18%) were teased about how their face looks
      in the past month. CONCLUSIONS: Stigma experiences were frequently reported by
      youth with facial differences and were correlated with independent parental
      report. This level of stigma suggests that media and public health interventions
      may be warranted to reduce discrimination, prejudice and negative adolescent
      social experiences related to facial difference.

PMID- 17552948
TI  - Planning for the future: can the core urologist provide safe and effective out-of
      hours cover?

PMID- 17552949
TI  - Bilateral synchronous sporadic renal cell carcinoma: surgical management,
      oncological and functional outcomes.
AB  - OBJECTIVE: To analyse the functional and oncological outcomes of surgical
      treatment of bilateral synchronous sporadic renal cell carcinoma (RCC). PATIENTS
      AND METHODS: Between 1969 and 2006, 57 patients with bilateral synchronous
      sporadic RCC were identified from our kidney database. The mean (range) follow-up
      was 4.8 (0.1-23.8) years; 28 patients (49%) had radical nephrectomy (RN) and
      contralateral nephron-sparing surgery (NSS), and 22 (39%) had bilateral NSS. The
      oncological outcome and long-term renal function were analysed. RESULTS: After
      excluding four patients (7%) with bilateral benign renal tumours, six (11%) with
      metastatic bilateral RCC and three (5%) who had bilateral RN, the cancer-specific
      outcome was analysed. For 44 patients with bilateral RCC who had surgery with
      intent to cure and avoid dialysis, 13 (30%) had stage pT1a, 10 (23%) pT1b, nine
      (17%) pT2 and 12 (27%) pT3 disease. At 5 and 10 years, the cancer-specific
      survival rates were 86% and 75%, and the local recurrence-free survival rates
      were 87% and 80%. The median serum creatinine level at the latest follow-up was
      1.18 mg/dL in patients after bilateral NSS and 1.40 mg/dL after unilateral NSS
      and contralateral RN (P < 0.05). CONCLUSIONS: These long-term data support the
      concept that NSS, whenever possible bilateral, is the treatment of choice for
      bilateral synchronous sporadic RCC. NSS provides adequate local tumour control
      and cancer-specific survival. Preservation of renal function is more efficient
      with bilateral NSS than with unilateral NSS and contralateral RN.

PMID- 17552950
TI  - The utility of lactate dehydrogenase in the follow-up of testicular germ cell
      tumours.
AB  - OBJECTIVE: To evaluate the utility of lactate dehydrogenase (LDH), a tumour
      marker that is frequently elevated at diagnosis and relapse of testicular germ
      cell tumours (TGCTs), in the follow-up of TGCTs for detecting tumour relapse, as
      it has role as a prognostic factor but its role in follow-up is less certain.
      PATIENTS AND METHODS: We retrospectively reviewed 499 patients with TGCT who were
      followed from 1 January 2004 to 31 December 2005, with no clinical evidence of
      disease after a complete response to treatment or on surveillance for stage I
      disease. RESULTS: Of patients attending for follow-up or surveillance, in 26 of
      1777 (1.4%) "patient-visits" there was a high LDH level related to disease, and
      in 137 of 1777 (7.7%) such visits there was a high LDH from unrelated causes. Of
      the 499 patients who were followed, 15 relapsed; the LDH level was high in six of
      15 who relapsed, with LDH being one of the first elevated markers in four and the
      only elevated marker in one (seminoma). Of the 449 patients, 41 (9.1%) had a
      persistent false-positive increase in LDH. The sensitivity of LDH was 40%, the
      specificity 90.5% and the positive predictive value 12.8% to detect relapse of
      disease during the follow-up of TGCTs. When the series of 116 relapsed patients
      from 1992 to 2005 was analysed, an increase in LDH facilitated the detection of
      relapse in 2% of non-seminomatous GCTs and 11% of seminomas, independent of other
      markers. CONCLUSION: LDH has limited sensitivity, specificity and positive
      predictive value for detecting relapse of TGCT and false-positive increases are
      common. An elevated LDH level contributed to the detection in six of 15 relapses,
      suggesting that its value in the follow-up of TGCT might be useful if interpreted
      cautiously. High LDH levels during the follow-up might require repeat serial LDH
      estimates to confirm the elevation, and imaging to detect a relapse.

PMID- 17552951
TI  - The increasing use of intravesical therapies for stage T1 bladder cancer
      coincides with decreasing survival after cystectomy.
AB  - OBJECTIVE: Intravesical therapy (IVT), chemo and immunotherapy, has made
      conservative, bladder-sparing strategies a viable option for managing patients
      with high grade T1 bladder cancer. However, many of these patients will have
      recurrence and occasionally progression, questioning delayed intervention. This
      study examines the patterns of use of IVT in high-grade T1 bladder cancer and the
      subsequent impact on survival for patients ultimately proceeding to radical
      cystectomy (RC). PATIENTS AND METHODS: Between 1990 and 2005, 104 patients were
      identified with T1 high-grade transitional cell carcinoma (TCC) and who underwent
      RC. Patients were divided into two groups; those having RC before 1998 (median
      year of surgery) and those after 1998. Trends in time from diagnosis to RC,
      courses of IVT, recurrence and pathological stage were analysed using two-sample
      t-tests with 95% confidence intervals. Kaplan-Meier analysis was used to
      determine the disease-free and overall survival rates. RESULTS: Before 1998, 28
      of 38 patients (74%) proceeded directly to RC with no IVT, vs 20 of 47 (43%)
      after 1998 (P = 0.004). The mean number of IVT courses per patient was 0.53
      before 1998 and 1.2 afterward (P = 0.016). Patients who had RC before 1998 had a
      69.7% disease-free survival at 5 years, vs 39.6% for those after 1998 (P = 0.05).
      CONCLUSION: In the past 15 years, our experience indicates that patients having
      RC for T1 high-grade TCC after 1998 were more likely to receive IVT. These same
      patients had a worsening disease-free survival. In very few other cancers has
      disease-free survival decreased over time. We postulate that the decrease in
      survival might be related to an increased use of IVT.

PMID- 17552952
TI  - Real-time elastography for detecting prostate cancer: preliminary experience.
AB  - OBJECTIVE: To assess the use of real-time elastography (RTE) for detecting
      prostate cancer in patients scheduled for radical prostatectomy (RP), as most
      solid tumours differ in their consistency from the deriving tissue, and RTE might
      offer a new tool for cancer detection. PATIENTS AND METHODS: We examined 15
      patients (mean age 56 years, sd 6.2, range 46-71) with RTE, using an
      ultrasonography (US) system with a 7.5-MHz transrectal probe as a transducer. RTE
      is capable of visualizing displacements between pairs of US images of tissues
      when placed under axial compression. The stiffness of the lesion was displayed
      from blue (soft) to black (hard). Hard lesions with a diameter of > or = 5 mm
      were considered as malignant. All patients had the diagnosis of prostate cancer
      confirmed by biopsy and had a mean (range) prostate specific antigen (PSA) level
      of 4.6 (1.4-16.1) ng/mL; all were scheduled for RP. US was performed by two
      investigators and interpreted by consensus. Cancer location and size was
      determined in the RTE mode only. One pathologist classified tumour location,
      grade and stage. The RTE findings were compared with the pathological findings.
      RESULTS: There were no major complications during RP in any patient; all had a
      pT2 tumour on histopathological examination, the Gleason score was 5-9 and the
      mean (range) tumour size 1.1 (0.6-2.5) cm. Thirty-five foci of prostate cancer
      were present at the pathological evaluation; multiple foci were found in 11 of
      the 15 glands. RTE detected 28 of 35 cancer foci (sensitivity 80%). The per
      patient analysis showed that RTE detected at least one cancer area in each of the
      15 patients. Only four sites with false-positive findings on RTE and no
      histopathological correlation were detected; these findings were obtained in the
      first five patients (period of learning). CONCLUSIONS: RTE can be used to
      visualize differences in tissue elasticity. Our results show that RTE allows the
      detection of prostate cancer and estimation of tumour location and size. RTE of
      the prostate is a new imaging method with great potential for detecting prostate
      cancer.

PMID- 17552953
TI  - Comparison of a 3-day with a 1-day regimen of an extended-release formulation of
      ciprofloxacin as antimicrobial prophylaxis for patients undergoing transrectal
      needle biopsy of the prostate.
AB  - OBJECTIVE: To compare the clinical and bacteriological efficacy and the clinical
      safety of a 1-day with a 3-day regimen of an extended-release formulation of
      ciprofloxacin (ciprofloxacin XR) given as antimicrobial prophylaxis to men
      undergoing transrectal needle biopsy of the prostate (TRNBP). PATIENTS AND
      METHODS: This was a multicentre, prospective, international, double-blind study
      in patients who required TRNBP. Patients were randomized to receive oral
      ciprofloxacin XR 1000 mg as either a 1-day or a 3-day regimen. Single doses were
      given at 24 h before, 2-3 h before, and 24 h after TRNBP. Patients in the 1-day
      regimen had placebo instead of the first and third doses of ciprofloxacin.
      RESULTS: Of 497 patients enrolled, 247 were randomized to 1-day ciprofloxacin XR
      and 250 to the 3-day regimen. In the population valid for microbiological
      efficacy, the final assessment identified bacteriological success (primary
      efficacy endpoint) in more patients who had the 3-day regimen (98%) than in those
      who received the 1-day regimen (94.8%, 95% confidence interval, CI, - 6.1%,
      0.8%), although the difference was not statistically significant. In this
      population, the clinical response at the final visit was 98.5% and 96.7% for
      patients receiving the 3-day and the 1-day regimens, respectively (95% CI - 5.2%,
      0.8%). However, in the clinical efficacy population the clinical success rate was
      significantly greater for the 3-day (99.0%) than for the 1-day regimen (95.8%;
      95% CI - 6.4%, - 0.3%). In a multivariate analysis, patients with diabetes
      mellitus and patients with a history of prostatitis had higher microbiological
      and clinical failure rates, respectively, than those without such conditions. For
      these patients, all failures occurred among those treated with the 1-day regimen.
      CONCLUSION: As defined by bacteriological success in the population assessed for
      microbiological efficacy, prophylaxis with one dose of ciprofloxacin XR was
      statistically no worse than a 3-day regimen. However, in all efficacy analyses,
      bacteriological and clinical success rates were consistently lower for the 1-day
      than for the 3-day treatment. Thus, for selected patients undergoing TRNBP, there
      might be a role for 3-day preventive therapy with ciprofloxacin XR.

PMID- 17552954
TI  - A randomized prospective trial evaluating testosterone, haemoglobin kinetics and
      quality of life, during and after 12 months of androgen deprivation after
      prostatectomy: results from the Postoperative Adjuvant Androgen Deprivation
      trial.
AB  - OBJECTIVE: To assess testosterone and haemoglobin kinetics in the Postoperative
      Adjuvant Androgen Deprivation (PAAD) trial, and correlate these with quality of
      life (QoL) in this prospective randomized study. PATIENTS AND METHODS: Forty
      three patients met the criteria for high-risk cancer after RRP (Gleason score >
      or = 8, pT3c or Gleason score 7 concomitant with pT3a/b and positive surgical
      margins) and were prospectively randomized to either observation or AD for 12
      months. Haemoglobin and testosterone levels were determined and QoL surveyed at
      regular intervals for 24 months. RESULTS: Serum testosterone levels were castrate
      in 19 of 21 treated patients at 3 months and all at 6 months after starting AD.
      Levels failed to return to normal at 6 months after stopping treatment in six of
      16 (38%) patients, and at 12 months in three of 17 (18%). AD caused a delay in
      the recovery of haemoglobin levels to normal after RRP. There was no
      statistically significant decline in the Short Form-36 QoL score with AD. Scores
      on the University of California-Los Angeles Sexual Functioning Scale were
      decreased during AD, but returned to a level not statistically significantly
      different from controls after stopping treatment. CONCLUSION: A year of adjuvant
      AD after RRP affected serum haemoglobin, testosterone and sexual function
      reversibly, with return to control levels within the subsequent year in most
      patients. No significant effect on overall QoL with AD was detected in the study.

PMID- 17552956
TI  - The impact of targeted training, a dedicated protocol and on-site training
      material in reducing observer variability of prostate and transition zone
      dimensions measured by transrectal ultrasonography, in multicentre multinational
      clinical trials of men with symptomatic benign prostatic enlargement.
AB  - OBJECTIVE: To assess the variability of a standardized protocol of transrectal
      ultrasonography (TRUS), with targeted training, and compare it to the variability
      in other multicentre clinical trials, as TRUS-estimated total prostate volume
      (TPV) and transition zone volume (TZV) are considered important efficacy
      endpoints in assessing new drug therapies for benign prostatic enlargement (BPE),
      but standardizing TRUS remains a challenge in such studies. PATIENTS AND METHODS:
      In all, 174 patients with BPE in the placebo arm of a 30-centre clinical trial
      were analysed at baseline, 13 and 26 weeks with TRUS, to extract TPV and TZV
      values. All TRUS operators received training in the standardized methods, which
      was supplemented at the outset by a compact disc-based video. RESULTS: The mean
      (sd) changes from baseline in TPV at 13 and 26 weeks were - 2.9 (8.9) and -1.9
      (8.5) mL, respectively; the respective mean changes from baseline in TZV were 
      1.2 (6.4) and + 0.7 (7.8) mL. For TPV, 80% of the measurements had differences of
      + 5.2 to -13.4 mL at 13 weeks, and + 8.0 to - 10.9 mL at 26 weeks. For TZV, 80%
      of the differences were + 5.8 to - 7.4 at 13 weeks, and + 9.3 to -6.5 mL at 26
      weeks. CONCLUSION: The performance of TRUS compared favourably with similar
      published multicentre studies, which we suggest relates in part to the careful
      implementation of the protocol. We showed that diligent implementation of a
      detailed protocol, supplemented by targeted training of investigators and
      provision of on-site training material, promoted consistent acquisition and
      successful derivation of key clinical trial endpoints. Quantifying the
      variability of such endpoints will enable us to track deployment quality for
      future clinical trials, and will ensure that trials are sufficiently powered to
      define small changes in prostate size.

PMID- 17552955
TI  - Suppression of bone density loss and bone turnover in patients with hormone
      sensitive prostate cancer and receiving zoledronic acid.
AB  - OBJECTIVE: To report a randomized, placebo-controlled study of treatment with
      zoledronic acid every 3 months in patients with hormone-sensitive prostate
      cancer, both with and without bone metastases, to assess the effect on bone
      mineral density (BMD) and markers of bone turnover. PATIENTS AND METHODS:
      Eligible patients included those with prostate cancer and on androgen-deprivation
      therapy for <12 months. Patients received zoledronic acid 4 mg intravenously, or
      placebo, every 3 months for four treatments. BMD, urinary N-telopeptides of type
      I collagen (NTX), and serum bone alkaline phosphatase (BAP) were measured every 3
      months. In all, 42 patients were randomized. RESULTS: After excluding BMD data
      from sites of known metastases, patients receiving zoledronic acid had a relative
      increase in BMD compared with those receiving placebo, of 4.2% and 7.1% at the
      femoral neck and lumbar spine, respectively. NTX and BAP decreased significantly
      in patients receiving zoledronic acid. NTX and BAP levels were significantly
      higher at baseline in patients with bone metastases than in those without.
      CONCLUSIONS: Treatment with zoledronic acid every 3 months preserved bone density
      and suppressed markers of bone turnover in patients with androgen-deprived
      prostate cancer, both with and without bone metastases.

PMID- 17552957
TI  - The clinical efficacy of tolterodine extended-release is maintained for 24 h in
      patients with overactive bladder.
AB  - OBJECTIVE: To assess the 24-h efficacy of tolterodine extended-release (ER) in
      patients with overactive bladder (OAB) and urgency urinary incontinence (UUI).
      PATIENTS AND METHODS: We conducted a post hoc analysis of a 12-week, placebo
      controlled trial of tolterodine-ER in patients with frequency (> or =8 voids/24
      h) and UUI (> or=5 episodes/week) for > or = 6 months. Seven-day bladder diaries
      were used to record diary endpoints; 24-h diary data were stratified by 6-h
      periods beginning at midnight. RESULTS: Compared with placebo (508 patients),
      tolterodine-ER (507 patients) significantly and consistently increased volume
      voided per void and reduced UUI episodes and micturition frequency during each
      interval. CONCLUSIONS: These results indicate that tolterodine-ER maintained
      clinical efficacy over 24 h and should be effective for OAB symptoms without
      regard to whether symptoms occur during the day or at night.

PMID- 17552958
TI  - The reliability of the frequency-volume chart in assessing lower urinary tract
      symptoms.
AB  - OBJECTIVE: To assess the test-retest reliability of a 1-day frequency-volume
      chart (FVC) in men with lower urinary tract symptoms (LUTS). PATIENTS AND
      METHODS: Men with uncomplicated LUTS presenting to a urology clinic were asked to
      complete FVCs on three consecutive days. Standard measures of voiding frequency
      and volume were derived using International Continence Society definitions. Test
      retest reliability of 1-day voiding behaviour was evaluated with an intraclass
      correlation coefficient (ICC). We also derived 95% confidence intervals (CI) for
      each measure, thereby indicating the precision of the measurements produced by a
      1-day chart. RESULTS: Of 140 patients with LUTS enrolled, 96 patients (69%)
      completed three 1-day FVCs. The frequency and volume measures typically had ICCs
      of 0.7-0.8; the "number of urgent voids" had the highest ICC. Nocturnal frequency
      and nocturnal volume were less reliable, with ICCs of 0.59 and 0.60,
      respectively. However, the 95% CIs around patient measurements tended to be wide.
      For 24-h voiding frequency, the true value for a patient might be up to +/- three
      voids away from the observed value for 95% of patients. CONCLUSION: The measures
      of voiding behaviour derived from 1-day FVCs had sufficient test-retest
      reliability to differentiate between high and low levels of voiding symptoms.
      However, individual measurements could be imprecise, suggesting that, in men with
      LUTS, a 1-day FVC cannot be used for diagnosis, or monitoring changes in symptom
      scores after treatment.

PMID- 17552959
TI  - Analysis of the efficacy and safety of sildenafil citrate in the geriatric
      population.
AB  - OBJECTIVE: To define the efficacy and tolerability of sildenafil in elderly men,
      as epidemiological data show an increasing life-expectancy of the population, and
      age is not only correlated with increasing morbidity but also an increase in the
      prevalence of erectile dysfunction (ED), for which sildenafil, available for >8
      years, is effective and safe across a wide variety of medical comorbidities,
      severity and causes of ED. PATIENTS AND METHODS: A database was generated from
      all sildenafil users in one sexual medicine practice, and data were extracted for
      men aged >60 years. The database included data on patient demographics,
      comorbidities, International Index of Erectile Function (IIEF) scores and adverse
      events (AEs). The patients were subdivided into those aged 60-69 (group 1), 70-79
      (group 2), and > or = 80 years (group 3). Analysis of variance was used to assess
      differences among the three groups for several variables of demographics and
      erectile response. RESULTS: In all, 167 patients were analysed; there were no
      significant differences in the duration of ED (5 +/- 3 years) or presence of
      comorbidities among the three groups. With a mean of two risk factors, the
      overall incidence of comorbidities was hypertension in 37%, dyslipidaemia in 28%,
      diabetes in 26%, coronary artery disease in 18% and lower urinary tract symptoms
      in 46%. The efficacy data showed that overall, 54% of men responded to
      sildenafil, with a mean increase in IIEF EF domain score of 5.7. Within the three
      groups there was a significant age-related decrease in response rate and IIEF EF
      domain score with age. However, there was no difference in AE incidence among the
      three groups, with an overall profile of 18% headache, 8% flushing, 8% dyspepsia,
      5% nasal congestion and 2% visual changes. No overt cardiovascular events were
      reported. CONCLUSIONS: From these data, sildenafil is an effective agent in
      elderly men, but had a lower efficacy rate with increasing age, especially in men
      aged >80 years. The incidence of side-effects was similar to that in the general
      population taking sildenafil, with no difference in AEs among the different age
      groups.

PMID- 17552960
TI  - Factors associated with preference for sildenafil citrate and tadalafil for
      treating erectile dysfunction in men naive to phosphodiesterase 5 inhibitor
      therapy: post hoc analysis of data from a multicentre, randomized, open-label,
      crossover study.
AB  - OBJECTIVES: To determine if baseline characteristics, treatment efficacy,
      psychosocial outcomes or tolerability were associated with patient preference for
      sildenafil citrate (sildenafil) or tadalafil for treating erectile dysfunction
      (ED) in men naive to phosphodiesterase 5 inhibitor therapy. PATIENTS AND METHODS:
      In an open-label, crossover study of sildenafil (25, 50 or 100 mg) and tadalafil
      (10 or 20 mg), dosed as needed, after a 4-week baseline assessment, 367 men with
      ED were randomly assigned to sildenafil followed by tadalafil or vice versa (8
      week dose optimization and 4-week assessment phase for each treatment period).
      Patients completing both periods chose which treatment they preferred for an 8
      week extension phase. Bivariate logistic regression and stepwise logistic
      regression were used to determine if any baseline characteristics or post
      baseline measurements were associated with the patients' treatment preference.
      Baseline variables examined were age, race, ED aetiology/duration, body mass
      index, smoking status, alcohol consumption, vital signs, comorbid medical
      conditions, and baseline scores for the International Index of Erectile Function
      (IIEF) domains, Psychological and Interpersonal Relationship Scales (PAIRS)
      domains, and Sexual Encounter Profile (SEP) diary questions. Post-baseline
      variables examined were therapy sequence, dosage, and differences in IIEF and
      PAIRS domains, SEP scores, in number/timing of sexual attempts and in the
      severity of side-effects (overall patient perception). RESULTS: Of 291 patients
      completing both treatments and indicating a preference, 85 (29%) preferred
      sildenafil and 206 (71%) preferred tadalafil. Variables were individually
      analysed using bivariate analysis; one baseline characteristic (presence/absence
      of hyperlipidaemia) and 13 post-baseline measurements were significantly
      associated with the patients' treatment preference. Variables were analysed as a
      group using stepwise logistic regression; a set of six post-baseline factors was
      identified as significantly associated with patient preference. Dosage choice,
      reductions in the PAIRS time concerns domain, IIEF intercourse satisfaction
      domain improvements, smaller side-effect severity scores, more sexual attempts,
      and increased SEP4 scores (satisfaction with erection hardness) during the
      tadalafil or sildenafil treatment periods were all significantly associated with
      preference for tadalafil or sildenafil. CONCLUSIONS: We identified no baseline
      characteristics that prospectively distinguish patients who will prefer tadalafil
      or sildenafil. Patient differences in time concerns, dosage choice, intercourse
      satisfaction, treatment tolerability, number of sexual attempts and satisfaction
      with erection hardness were the set of factors most significantly associated with
      treatment preference, and the preference observed for tadalafil (71%) or
      sildenafil (29%) might be substantially accounted for by differences in these
      factors during the tadalafil and sildenafil treatment periods.

PMID- 17552961
TI  - Laparoscopic radical cystectomy for cancer: oncological outcomes at up to 5
      years.
AB  - OBJECTIVE: To report the oncological outcomes at < or = 5 years after
      laparoscopic radical cystectomy (LRC), as open RC is the reference standard
      treatment for muscle-invasive bladder cancer, but interest in LRC is increasing
      at selected centres worldwide and as yet there are no long-term follow-up data.
      PATIENTS AND METHODS: Between December 1999 and January 2005, 37 patients (mean
      age 66 years) had LRC with urinary diversion for invasive bladder cancer; 26
      patients (70%) also had an extended pelvic lymphadenectomy. Overall and cancer
      specific survival data were obtained from patient charts, radiographic reports,
      telephone contact, and a check of the Social Security Death Index. RESULTS: Most
      tumours were transitional cell carcinoma (32, 86%), high-grade (grade III in 29,
      78%) and high-stage (> or =pT2 in 26, 70%). Two patients had a positive surgical
      margin. The median (range) number of lymph nodes excised was 14 (2-24); seven
      patients (17%) had node-positive disease (pN1). Follow-up data were available for
      35 patients (95%); eight (22%) completed > or = 5 years of follow-up, and the
      mean (range) follow-up was 31 (1-66) months. At the last follow-up, 24 patients
      (65%) were alive with no evidence of disease and 11 (30%) were dead, two (5%)
      from metastasis and nine (24%) from unrelated causes. The 5-year actuarial
      overall, cancer-specific and recurrence-free survival was 63%, 92% and 92%,
      respectively. CONCLUSION: To our knowledge, this is the first report of < or = 5
      year follow-up after LRC; the data suggest that LRC provides oncological outcomes
      comparable to contemporary series of open RC.

PMID- 17552962
TI  - Management of calyceal diverticular stones with extracorporeal shock wave
      lithotripsy and percutaneous nephrolithotomy: long-term outcome.
AB  - OBJECTIVE: To review patients with an extended follow-up after extracorporeal
      shock wave lithotripsy (ESWL) or percutaneous nephrolithotomy (PCNL) for calyceal
      diverticular stones (CDS), over a 15-year period, assessing the long-term
      outcome. PATIENTS AND METHODS: In all, 56 patients were treated for symptomatic
      CDS disease by ESWL (38) or PCNL (18). The stone-bearing diverticula were in the
      upper calyces in 26, middle calyces in 24 and lower calyces in six patients, and
      in the right kidney in 22 and in the left in 34. The most frequent symptom was
      ipsilateral flank pain (84%) and 32% of patients presented with associated
      chronic urinary tract infections. In a retrospective analysis, we assessed stone
      size, diverticulum location, stone-free rate, symptom-free rate, complications
      and extended follow-up. RESULTS: In the short-term in the ESWL group, 21% of
      patients were stone-free and 61% were asymptomatic; 8% developed symptoms and 8%
      developed recurrence or stone-growth in the long term. There were six minor
      complications. In the PCNL group, 15 patients (83%) were stone-free in the short
      term; two had a recurrence (11%) and two had stone growth (11) in the long term.
      There were three complications after PCNL. CONCLUSIONS: This series shows that
      PCNL is an effective and durable means of treating CDS, regardless of stone size
      or location of the diverticulum. Despite low stone-free rates with ESWL, most
      patients were rendered symptom-free with minimal complications. The long-term
      recurrence rates, 8% for ESWL and 11% for PCNL, were comparable.

PMID- 17552963
TI  - Intrarenal manipulation of flexible ureteroscopes: a comparative study.
AB  - OBJECTIVE: To compare the relative ease of manipulation around a calyceal model
      in the hands of experienced ureteroscopists of four flexible ureteroscopes (FUs),
      as new-generation FUs provide exaggerated active deflection to facilitate
      intrarenal manipulation. SUBJECTS AND METHODS: Four FUs of <7.5 F were tested:
      the FlexVision U-500 (SF) (Stryker Endoscopy, San Jose, CA, USA), the Dur-8 Elite
      (D8E) (ACMI, Southborough, MA, USA), the Viper (Richard Wolf Medical Instruments,
      Vernon Hills, IL, USA) and the URF-P3 (Olympus Surgical, Orangeburg, NY, USA).
      Eight experienced ureteroscopists, each with a minimum of 100 flexible
      ureteroscopies over the preceding 3 years, assessed the FUs. The Mediskills
      calyceal model represents a moderately hydronephrotic collecting system, with a
      renal pelvic width of 2 cm, infundibular widths of 1 cm and infundibular lengths
      of 2 cm. The middle calyx infundibular angle was 80 degrees and the lower calyx
      infundibular angle was 100 degrees . The model does not allow for significant
      passive secondary deflection. The surgeons manoeuvred systematically around a
      four-point course, from the pelvi-ureteric junction, to anterior lower calyx, to
      anterior middle calyx, to posterior lower calyx, to posterior middle calyx,
      touching a metal sensor with an fulguration electrode, to trigger an automated
      signal at each calyx. The order of FU used by each surgeon was randomized. Each
      surgeon performed the course twice with each FU, ending with the first FU they
      started with, to diminish the impact of "learning the course". RESULTS: There
      were significant differences in the mean (sd) total time for manipulation through
      the four-point course, for the Viper, SF, D8E and URF-P3, at 29 (11), 37 (23), 38
      (20) and 50 (24) s, respectively (P = 0.034). The URF-P3 took longer to reach the
      posterior lower pole, at 18.1 (14.5) s than the Viper, SF and D8E, at 6.3 (2.8)
      (P = 0.004), 6.6 (3.3) (P = 0.008) and 7.7 (4.9) (P = 0.008), respectively. The
      Viper was quicker to reach the posterior middle pole, at 7.3 (4.0) s, than the
      URF-P3, SF and D8E, at 14.9 (13.1) (P = 0.036), 14.7 (14.3) (P = 0.056) and 12.7
      (14.0) s (P = 0.115), respectively. Subjectively, six of eight endoscopists
      stated that the Viper was the better FU for ease of manipulation, while five of
      eight stated that the URF-P3 was the most difficult. Notably, all eight
      endoscopists had more clinical experience with the URF-P3 than with the other
      three FUs tested. CONCLUSIONS: In a model of a moderately hydronephrotic kidney
      with long infundibulum and limited ability to perform passive secondary
      deflection, FUs with exaggerated active deflection outmanoeuvred the URF-P3. The
      Viper was better for manipulation in the hands of experienced endoscopists.

PMID- 17552964
TI  - A porcine model of bladder outlet obstruction incorporating radio-telemetered
      cystometry.
AB  - OBJECTIVE: To present a novel porcine model of bladder outlet obstruction (BOO)
      with a standardized bladder outlet resistance and real-time ambulatory radio
      telemetered cystometry, as BOO is a common condition with many causes in both
      adults and children, with significant morbidity and occasional mortality, but
      attempts to model this condition in many animal models have the fundamental
      problem of standardising the degree of outlet resistance. MATERIALS AND METHODS:
      BOO was created in nine castrated male pigs by dividing the mid-urethra; outflow
      was allowed through an implanted bladder drainage catheter containing a
      resistance valve, allowing urine to flow across the valve only when a set
      pressure differential was generated across the valve. An implantable radio
      telemetered pressure sensor monitored the pressure within the bladder and
      abdominal cavity, and relayed this information to a remote computer. Four control
      pigs had an occluded bladder drainage catheter and pressure sensor placed, but
      were allowed to void normally through the native urethra. Intra-vesical pressure
      was monitored by telemetry, while the resistance valve was increased weekly,
      beginning with 2 cmH2O and ultimately reaching 10 cmH2O. The pigs were assessed
      using conventional cystometry under anaesthesia before death, and samples
      conserved in formalin for haematoxylin and eosin staining. RESULTS: The pigs had
      radio-telemetered cystometry for a median of 26 days. All telemetry implants
      functioned well for the duration of the experiment, but one pig developed a
      urethral fistula and was excluded from the study. With BOO the bladder mass index
      (bladder mass/body mass x 10 000) increased from 9.7 to 20 (P = 0.004), with a
      significant degree of hypertrophy of the detrusor smooth muscle bundles.
      Obstructed bladders were significantly less compliant than control bladders (8.3
      vs 22.1 mL/cmH2O, P = 0.03). Telemetric cystometry showed that there was no
      statistically significance difference in mean bladder pressure between obstructed
      and control pigs (4.8 vs 6.7 cmH2O, P = 0.7), but that each void was longer in
      the pigs with BOO. CONCLUSION: This new model of BOO provides a method of
      reliably and precisely defining the bladder outlet resistance; it induces the
      changes classically seen with BOO, including increased bladder mass, increased
      smooth muscle bundle size and decreased compliance.

PMID- 17552965
TI  - Apoptosis induction is associated with decreased NHE1 expression in neonatal
      unilateral ureteric obstruction.
AB  - OBJECTIVE To examine the participation of NHE1 in the regulation of the apoptotic
      response in neonatal obstruction, as the ubiquitously expressed NHE1 isoform is
      an important component of regulatory volume increase. MATERIALS AND METHODS Rats
      had a unilateral ureteric obstruction (UUO) or a sham operation, and the kidneys
      were harvested 5 and 14 days afterward. Cellular apoptosis in proximal tubules
      (PT) and collecting ducts (CD) was assessed using a standard assay, and NHE1
      expression in the renal cortex assessed using reverse transcription-polymerase
      chain reaction and Western blots. Mitochondrial apoptosis was evaluated by
      Bax/BcL2 expression, and caspase-3 expression and activity. In addition, we
      evaluated the in vivo administration of increasing doses of 5-(N-ethyl-N
      isopropyl)-amiloride (EIPA) on NHE1 inhibition associated with the induction of
      apoptosis. RESULTS After 14 days there were consistently more apoptotic cells in
      CD than in PT, associated with a lower expression of NHE1 at the mRNA and protein
      levels. There was increased expression of the Bax/BcL2 ratio, linked to decreased
      pro-caspase-3 protein levels and with increased caspase-3 activation. NHE1
      inhibition by increasing doses of EIPA induced epithelial cell apoptosis and
      increased caspase-3 activity in a dose-dependent manner. After in vitro
      incubation with amiloride (100 mm) there was less NHE1 expression associated with
      reduced 32 kDa pro-caspase-3 protein levels. Kidneys obstructed for 5 days showed
      no changes in NHE1 expression or induction of apoptosis. CONCLUSION In neonatal
      obstruction, we suggest that the decreased NHE1 expression could be a signal
      transduction event participating in the induction of epithelial tubular cell
      apoptosis, through the regulation of the BcL-2 gene family and activation of
      caspase-3.

PMID- 17552966
TI  - Does it do what it says on the tin?

PMID- 17552967
TI  - Penile erection of pathological source; semantically a better term for priapism.

PMID- 17552968
TI  - The "learning curve" in hypospadias surgery.

PMID- 17552969
TI  - Fine-touch pressure thresholds in the adult penis.

PMID- 17552970
TI  - Working party for urological studies in improving minimally invasive skill
      acquisition and delivery.

PMID- 17552971
TI  - Multifocal nonmetastatic renal cell carcinoma in laparoscopic and open partial
      nephrectomy.

PMID- 17552974
TI  - Distal penile circular fasciocutaneous flap for complex anterior urethral
      strictures.

PMID- 17552975
TI  - Supine Valdivia and modified lithotomy position for simultaneous anterograde and
      retrograde endourological access.

PMID- 17552976
TI  - Are point-of-care (POC) virological tests what is needed?
AB  - Point-of-care (POC) tests are becoming more available, although the way in which
      they should be used is currently undecided. Any 'laboratory'-based diagnosis of
      respiratory infections has three components: the specimen taken, the test used,
      and the interpretation of the results. Each of these components needs to be
      carefully addressed when using POC tests for the diagnosis of respiratory tract
      infections. Given the enthusiasm with which POC tests are being developed, it is
      likely that they will be used more and more widely. If so, the advantages and
      limitations of their use should be fully discussed and the implications
      recognised.

PMID- 17552977
TI  - Establishment of Liebermannia dichroplusae n. comb. on the basis of molecular
      characterization of Perezia dichroplusae Lange, 1987 (Microsporidia).
AB  - Perezia dichroplusae Lange, 1987 is a parasite of the Malpighian tubules of an
      Argentine grasshopper, Dichroplus elongatus (Orthoptera, Acrididae,
      Melanoplinae). In order to determine relationships of this microsporidium with
      Perezia nelsoni and with other microsporidia, we sequenced its small subunit
      ribosomal RNA gene (SSU rDNA) (GenBank Accession No. EF016249) and performed
      phylogenetic analysis of the novel sequence against 17 microsporidian SSU rDNA
      sequences from GenBank, using neighbor-joining (NJ), maximum-parsimony (MP), and
      maximum-likelihood (ML) methods. This analysis revealed the highest similarity
      (96%) of the new sequence to Liebermannia patagonica, a parasite of gut
      epithelium cells of another grasshopper from Argentina, versus only 65%
      similarity to P. nelsoni, a parasite of muscles of paenaeid shrimps. In
      phylogenetic trees inferred from SSU rDNA sequences, the microsporidium from D.
      elongatus is sister taxon to L. patagonica and both cluster with Orthosomella
      operophterae. At the higher hierarchical level, the Liebermania-Orthosomella
      branch forms a clade with the Endoreticulatus-Cystosporogenus-Vittaforma group
      and with Enterocytozoon bieneusi. Perezia nelsoni falls into another large clade
      together with Nosema and Ameson species. We propose transferring P. dichroplusae
      to the genus Liebermannia and creating a new combination Liebermannia
      dichroplusae n. comb., based both on SSU rDNA sequence analysis and on common
      characters between P. dichroplusae and L. patagonica, which include the presence
      of elongated multinuclear sporonts, sporoblastogenesis by a similar process of
      sequentially splitting off sporoblasts, ovocylindrical spores of variable size,
      tissue tropism limited to epithelial cells, Orthoptera as hosts, and geographical
      distribution of hosts in the southern temperate region of Argentina. We argue
      that the condition of the nuclei in spores (i.e. diplokaryotic in L. patagonica
      or monokaryotic in L. dichroplusae) cannot be used to distinguish genera.
      Therefore, we remove the statement about the presence of diplokaryotic spores
      from the revised diagnosis of the genus Liebermannia.

PMID- 17552978
TI  - Feeding by the Pfiesteria-like heterotrophic dinoflagellate Luciella masanensis.
AB  - To explore the feeding ecology of the Pfiesteria-like dinoflagellate (PLD)
      Luciella masanensis (GenBank Accession no. AM050344, previously Lucy), we
      investigated the feeding behavior and the kinds of prey species that L.
      masanensis fed on and determined its growth and ingestion rates of L. masanensis
      when it fed on the dinoflagellate Amphidinium carterae and an unidentified
      cryptophyte species (equivalent spherical diam., ESD=5.6 microm), which were the
      dominant phototrophic species when L. masanensis and similar small heterotrophic
      dinoflagellates were abundant in Masan Bay, Korea in 2005. Additionally, these
      parameters were also measured for L. masanensis fed on blood cells of the perch
      Lateolabrax japonicus and the raphidophyte Heterosigma akashiwo in the
      laboratory. Luciella masanensis fed on prey cells by using a peduncle after
      anchoring the prey with tow filament, and was able to feed on diverse prey such
      as cryptophytes, raphidophytes, diatoms, mixotrophic dinoflagellates, and the
      blood cells of fish and humans. Among the prey species tested in the present
      study, perch blood cells were observed to be the optimal prey for L. masanensis.
      Specific growth rates of L. masanensis feeding on perch blood cells, A. carterae,
      H. akashiwo, and the cryptophyte, either increased continuously or became
      saturated with increasing the mean prey concentration. The maximum specific
      growth rate of L. masanensis feeding on perch blood cells (1.46/day) was much
      greater than that of A. carterae (0.59/day), the cryptophyte (0.24/day), or H.
      akashiwo (0.20/day). The maximum ingestion rate of L. masanensis on perch blood
      cells (2.6 ng C/grazer/day) was also much higher than that of A. carterae (0.32
      ng C/grazer/day), the cryptophyte (0.44 ng C/grazer/day), or H. akashiwo (0.16 ng
      C/grazer/day). The kinds of prey species which L. masanensis is able to feed on
      were the same as those of Pfiesteria piscicida, but very different from those of
      another PLD Stoeckeria algicida. However, the maximum growth and ingestion rates
      of L. masanensis on perch blood cells, A. carterae, H. akashiwo, and the
      cryptophyte were considerably lower than those of P. piscicida. Therefore, these
      three dinoflagellates may occupy different ecological niches in marine planktonic
      communities, even though they have a similar size and shape and the same feeding
      mechanisms.

PMID- 17552979
TI  - Variation in macronuclear genome content of three ciliates with extensive
      chromosomal fragmentation: a preliminary analysis.
AB  - The genome architecture of ciliates, including features such as nuclear dualism
      and large-scale genome rearrangements, impacts gene and genome evolution in these
      organisms. To better understand the structure of macronuclear chromosomes in
      ciliates with extensively processed chromosomes, a sample of complete
      macronuclear chromosomes was sequenced from three ciliate species: Metopus es
      (Class [Cl]: Armophorea), Nyctotherus ovalis (Cl: Armophorea), and Chilodonella
      uncinata (Cl: Phyllopharyngea). By cloning whole macronuclear chromosomes into a
      plasmid vector, we generated nine clones from each of M. es and C. uncinata, and
      37 clones from N. ovalis. Analysis of these macronuclear chromosomes provides
      insight into the evolution of genome features such as chromosome content, gene
      structure, and genetic code. Phylogenetic patterns can be found in telomere
      structure and codon usage, which are both more similar in M. es and N. ovalis
      than C. uncinata. In addition, we provide evidence of lateral transfer of a
      bacterial endo-beta-mannanase gene onto a M. es chromosome and report the
      discovery of a 42-bp conserved sequence motif within N. ovalis untranslated
      regions.

PMID- 17552980
TI  - Ultrastructure of Buddenbrockia allmani n. sp. (Myxozoa, Malacosporea), a
      parasite of Lophopus crystallinus (Bryozoa, Phylactolaemata).
AB  - Development of a new species of malacosporean myxozoan (Buddenbrockia allmani n.
      sp.) in the bryozoan Lophopus crystallinus is described. Early stages,
      represented by isolated cells or small groups, were observed in the host's body
      wall or body cavity. Multiplication and rearrangement of cells gave an outer cell
      layer around a central mass. The outer cells made contact by filopodia and
      established adherens junctions. Sporoplasmosomes were a notable feature of early
      stages, but these were lost in subsequent development. Typical malacosporean sacs
      were formed from these groups by attachment of the inner (luminal) cells by a
      basal lamina to the outer layer (mural cells). Division of luminal cells gave
      rise to a population of cells that was liberated into the lumen of the sac.
      Mitotic spindles in open mitosis and prophase stages of meiosis were observed in
      luminal cells. Centrioles were absent. Detached luminal cells assembled to form
      spores with four polar capsules and several valve cells surrounding two
      sporoplasms with secondary cells. Restoration of sporoplasmosomes occurred in
      primary sporoplasms. A second type of sac was observed with highly irregular
      mural cells and stellate luminal cells. A radially striated layer and dense
      granules in the polar capsule wall, and previous data on 18 rDNA sequences
      enabled assignment of the species to the genus Buddenbrockia, while specific
      diagnosis relied on the rDNA data and on sac shape and size.

PMID- 17552981
TI  - Perkinsus olseni in vitro isolates from the New Zealand clam Austrovenus
      stutchburyi.
AB  - Perkinsus olseni infections are reported at 10%-84% prevalences among Austrovenus
      stutchburyi clams (cockles) in northern New Zealand coastal waters. However, P.
      olseni has not yet been propagated in vitro from New Zealand clams. In our sample
      of A. stutchburyi clams from Mangemangaroa Stream, New Zealand, 24% (8/34) showed
      low-intensity Perkinsus sp. infections among mantle and gill tissues incubated in
      alternative Ray's fluid thioglycollate medium (ARFTM), and 5% (4/79) showed
      Perkinsus sp. lesions by histological analyses. Among clams that were screened
      using a polymerase chain reaction (PCR) assay, 16% (3/19) were positive for
      Perkinsus sp. DNA. Alternative Ray's fluid thioglycollate medium-enlarged
      hypnospores from tissues of five infected clams yielded three in vitro Perkinsus
      sp. isolate cultures that were cloned before sequencing internal transcribed
      spacer (ITS) regions of their rRNA gene complex. For one isolate, ATCC PRA-205,
      large subunit (LSU) rRNA and actin genes were also sequenced. All nucleotide
      sequences from all isolates consistently identified them as P. olseni, as did
      their in vitro cell cycles and zoosporulation characteristics. All in vitro
      isolate cultures and their respective monoclonal derivative strains were
      cryopreserved and deposited for archiving and distribution by the American Type
      Culture Collection (http://www.atcc.org).

PMID- 17552982
TI  - Chemokinesis by tetrahymena in response to bacterial oligopeptides.
AB  - The ciliate Tetrahymena responds very efficiently by chemoattraction to a group
      of trichloroacetic acid-soluble oligopeptides isolated from a commercial
      bioprotein from Methanococcus. When fractionated by reversed phase C18-high
      pressure liquid chromatography, this group of very efficient chemoattractants
      turned out to consist of a heterogeneous group of oligopeptides with molecular
      weight ranging from 0.2 to 1.5 kDa. The peptides were very rich in the following
      amino acids: aspartic acid, alanine, glutamic acid, proline, glycine, lysine, and
      arginine. The term chemokinesis is used throughout to emphasise that
      chemoattraction does not necessarily include an element of orientation of cells.

PMID- 17552983
TI  - Micronuclear and macronuclear forms of beta-tubulin genes in the ciliate
      Chilodonella uncinata reveal insights into genome processing and protein
      evolution.
AB  - Chilodonella uncinata, like all ciliates, contains two distinct nuclei in every
      cell: a germline micronucleus and a somatic macronucleus. During development of
      the macronucleus from a zygotic nucleus, the genome is processed in several ways,
      including elimination of internal sequences. In this study, we analyze
      micronuclear and macronuclear copies of beta-tubulin in C. uncinata and find at
      least four divergent paralogs of beta-tubulin in the macronucleus. We
      characterize the micronuclear version of one paralog and compare its internally
      eliminated sequences (IESs) with previously described IESs in this species. These
      comparisons reveal the presence of a conserved sequence motif within IESs. In
      addition, we compare the sequences of beta-tubulin from C. uncinata with other
      ciliates and to other alveolates in order to test the hypothesis that the mode of
      molecular evolution in ciliates obscures phylogenetic signal in protein-coding
      genes. We find that heterogeneous rates of substitution in beta-tubulin across
      ciliates result in unstable genealogies that are inconsistent with phylogenies
      based on small subunit rDNA genes and on ultrastructure. We discuss the
      implications of our findings for genome processing and protein evolution in
      ciliates.

PMID- 17552984
TI  - Redescriptions of two marine hypotrichous ciliates, Diophrys irmgard and D.
      hystrix (Ciliophora, Euplotida), with a brief revision of the genus Diophrys.
AB  - Two insufficiently described marine euplotids, Diophrys irmgard Mansfeld (1923)
      and Diophrys hystrix Buddenbrock (1920), found in coastal waters near Qingdao,
      China, were reinvestigated with emphasis on their living morphology and
      infraciliature. Improved diagnoses and redescriptions are supplied for both
      organisms. Critical redefinitions of nine morphotypes are presented and the
      validities of the nominal species are discussed and briefly revised. Following
      Curds and Wu (1983), and based on data obtained during the present study and a
      critical review of the literature, five additional nominal species are regarded
      as junior synonyms of known forms: Diophrys quadricaudatus Agamaliev (1967), D.
      scutoides Agamaliev (1967), and D. tetramacronucleata Kattar (1970) are
      synonymized with D. scutum (Dujardin 1841), while D. pentacirratus Alekperov
      (1984) and D. multicirratus Alekperov (1984) are junior synonyms of D. oligothrix
      Borror (1965).

PMID- 17552985
TI  - Clathrin in Trypanosoma cruzi: in silico gene identification, isolation, and
      localization of protein expression sites.
AB  - Clathrin is a scaffold protein found in different types of coated vesicles in
      most eukaryotic cells. Major forces that drive clathrin coat formation are the
      adaptor protein complexes. Trypanosoma cruzi is a flagellate protozoan that
      ingests macromolecules through receptor-mediated endocytosis, but the molecules
      involved in this process are still poorly known. Bioinformatics was used to
      identify proteins in the T. cruzi genome database, permitting discrimination of
      the genes involved in clathrin coat assembly. Clathrin expression was
      demonstrated in T. cruzi epimastigotes by using several experimental approaches.
      Western blot analysis showed a single 180-kDa protein band, which corresponds to
      the molecular mass of mammalian clathrin heavy chain. A flow cytometry assay
      demonstrated that the clathrin heavy chain was expressed in 97.74% of the cell
      population analyzed, with a high-fluorescence signal. Immunofluorescence
      observation showed labeling clustered at the flagellar pocket and Golgi complex
      region. Coated vesicles budding off from the flagellar pocket and the trans Golgi
      network membranes were identified by transmission electron microscopy. Our data
      demonstrate the expression of clathrin in T. cruzi epimastigotes and show the
      association of this polypeptide with the parasite endocytic and exocytic
      pathways.

PMID- 17552986
TI  - Molecular phylogenetics of subclass Peritrichia (Ciliophora: Oligohymenophorea)
      based on expanded analyses of 18S rRNA sequences.
AB  - Phylogenetic relationships among peritrich ciliates remain unclear in spite of
      recent progress. To expand the analyses performed in previous studies, and to
      statistically test hypotheses of monophyly, we analyzed a broad sample of 18s
      rRNA sequences (including 15 peritrich genera), applying a conservative alignment
      strategy and several phylogenetic approaches. The main results are that: (i) the
      monophyly of Peritrichia cannot be rejected; (ii) the two main clades of
      Sessilida do not correspond to formally recognized taxa; (iii) the monophyly of
      genera Vorticella and Epistylis is significantly rejected; and (iv) morphological
      structures commonly used in peritrich taxonomy may be evolutionarily labile.

PMID- 17552987
TI  - Morphological descriptions of new and little-known benthic ciliates from Ganghwa
      tidal flat, Korea.
AB  - Ciliates are highly diverse in the benthos where there are rare species to be
      unrevealed and described. By isolating species during successive and diversified
      cultivations, we discovered several new and interesting taxa from the top layer
      sediment of a muddy site in the Ganghwa tidal flat. These include three new
      species Spirodysteria ganghwaensis n. sp., Uronemella parafilificum n. sp.,
      Zosterodasys minuta n. sp., and one poorly known form Loxophyllum
      chaetonotumBorror 1965. The morphology of live cells and infraciliature of these
      four species are described based on living observations, protargol impregnations,
      and morphometrics. Diagnoses and improved definitions are also provided. The
      newly established genus Spirodysteria n. g. differs from Dysteria mainly in its
      spirally twisted body shape. Spirodysteria kahli (Tucolesco 1962) n. comb.
      (formerly Dysteria kahliTucolesco 1962) has been included in this new genus.

PMID- 17552988
TI  - A molecular phylogenetic investigation of Opisthonecta and related genera
      (Ciliophora, Peritrichia, Sessilida).
AB  - The gene encoding 18S small subunit ribosomal RNA (ssu rRNA) was sequenced in the
      sessiline peritrichs Opisthonecta minima and Opisthonecta matiensis, whose free
      swimming, paedomorphic trophonts resemble telotrochs. Using these new sequences,
      phylogenetic trees were constructed with four different methods to test a
      previously published association between Opisthonecta henneguyi and members of
      the families Vorticellidae and Astylozoidae. All trees had similar topologies,
      with O. minima, O. henneguyi, Vorticella microstoma, and Astylozoon enriquesi
      forming a well-supported, certainly monophyletic clade. On the basis of genetic
      evidence, genera of the families Opisthonectidae and Astylozoidae are assigned to
      the family Vorticellidae, which already includes some species with free-swimming
      morphotypes. The ssu rRNA sequence of O. matiensis places it in the family
      Epistylididae; its taxonomic revision will be left to another group of authors. A
      close association of Ophrydium versatile with members of the family Vorticellidae
      was confirmed, casting doubt on the validity of the family Ophrydiidae. Epistylis
      galea, Campanella umbellaria, and Opercularia microdiscum are confirmed as
      comprising an extremely distinct, monophyletic, but morphologically heterogeneous
      clade that is basal to other clades of sessiline peritrichs.

PMID- 17552989
TI  - Challenging the omnipotence of the suprachiasmatic timekeeper: are circadian
      oscillators present throughout the mammalian brain?
AB  - The suprachiasmatic nucleus of the hypothalamus (SCN) is the master circadian
      pacemaker or clock in the mammalian brain. Canonical theory holds that the output
      from this single, dominant clock is responsible for driving most daily rhythms in
      physiology and behaviour. However, important recent findings challenge this
      uniclock model and reveal clock-like activities in many neural and non-neural
      tissues. Thus, in addition to the SCN, a number of areas of the mammalian brain
      including the olfactory bulb, amygdala, lateral habenula and a variety of nuclei
      in the hypothalamus, express circadian rhythms in core clock gene expression,
      hormone output and electrical activity. This review examines the evidence for
      extra-SCN circadian oscillators in the mammalian brain and highlights some of the
      essential properties and key differences between brain oscillators. The
      demonstration of neural pacemakers outside the SCN has wide-ranging implications
      for models of the circadian system at a whole-organism level.

PMID- 17552990
TI  - An antibody to synaptotagmin I facilitates synaptic transmission.
AB  - Proper functioning of the nervous system requires precise control of
      neurotransmitter release. Synaptotagmin, a synaptic vesicle protein, is crucial
      for the temporal control of neurotransmitter release. The mechanism of
      synaptotagmin function is still under debate. To investigate the mechanism by
      which synaptotagmin controls neurotransmitter release, we injected an antibody of
      rat synaptotagmin I into a crayfish motor axon. We found that the antibody
      enhanced synaptic transmission at crayfish neuromuscular junctions by increasing
      the amplitude of the evoked synaptic response. This effect was antibody-dose
      dependent. The antibody also reduced the rise time of the synaptic potentials.
      These effects were accompanied by a reduction in the Hill coefficient for Ca(2+)
      dependence of synaptic transmission. Our findings support the hypothesis that
      synaptotagmin inhibits neurotransmitter release in the absence of Ca(2+).

PMID- 17552991
TI  - Ethanol reverses the direction of long-term synaptic plasticity in the
      dorsomedial striatum.
AB  - The striatum is a critical structure for the control of voluntary behaviour, and
      striatal synaptic plasticity has been implicated in instrumental learning. As
      ethanol consumption can cause impairments in cognition, learning, and action
      selection, it is important to understand the effects of this drug on striatal
      function. In this study we examined the effects of ethanol on long-term synaptic
      plasticity in the dorsomedial striatum (DMS), a striatal subregion that plays a
      central role in the acquisition and selection of goal-directed actions. Ethanol
      was found to impair N-methyl-d-aspartic acid receptor (NMDAR)-dependent long-term
      potentiation (LTP) dose-dependently in the DMS, and to promote long-term
      depression (LTD) at the highest concentration (50 mm) used. These results suggest
      that ethanol, at a concentration usually associated with mild intoxication, could
      significantly change experience-dependent modification of corticostriatal
      circuits underlying the learning of goal-directed instrumental actions.

PMID- 17552992
TI  - Cellular localization and function of DARPP-32 in the rodent retina.
AB  - The goal of the present study was to elucidate the role of DARPP-32 (dopamine-
      and cyclic adenosine 3'-5'-monophosphate-regulated phosphoprotein, 32 kDa) in
      retinal function. We examined mouse and rat retinas for the presence of DARPP-32
      by immunocytochemistry. In both rodent retinas DARPP-32 immunoreactivity was
      localized to horizontal and AII amacrine neurons and to the Mueller glial cells,
      using immuno-double labelling. Additional unidentified neurons in the amacrine
      cell layer also showed DARPP-32 immunoreactivity. Using mice entrained to a 12-12
      h light-dark cycle, we found that exposure to light presented during the dark
      phase significantly enhanced phosphorylation of DARPP-32 at threonine (Thr) 34
      and phosphorylation of the ionotropic glutamate receptor subunit GluR1 at serine
      (Ser) 845, as measured by immunoblots. However, light also increased Ser 845
      GluR1 phosphorylation in DARPP-32-knockout mice. When a dopamine D1 receptor
      antagonist was injected into the eye prior to light exposure, phosphorylation of
      both Thr 34-DARPP-32 and Ser 845-GluR1 was significantly reduced. These data
      indicate that DARPP-32 participates in dopamine-mediated modifications of retinal
      function. We also tested for a possible circadian rhythm of Thr 34- and Thr 75
      DARPP-32 and Ser 845-GluR1 expression. No significant circadian rhythm of either
      DARPP-32 or GluR1 phosphorylation was found.

PMID- 17552993
TI  - Glutamatergic input is coded by spike frequency at the soma and proximal dendrite
      of AII amacrine cells in the mouse retina.
AB  - In the mammalian retina, AII amacrine cells play a crucial role in scotopic
      vision. They transfer rod signals from rod bipolar cells to the cone circuit, and
      divide these signals into the ON and OFF pathways at the discrete synaptic
      layers. AII amacrine cells have been reported to generate tetrodotoxin (TTX)
      sensitive repetitive spikes of small amplitude. To investigate the properties of
      the spikes, we performed whole-cell patch-clamping of AII amacrine cells in mouse
      retinal slices. The spike frequency increased in proportion to the concentration
      of glutamate puffer-applied to the arboreal dendrite and to the intensity of the
      depolarizing current injection. The spike activity was suppressed by L-2-amino-4
      phosphonobutyric acid, a glutamate analogue that hyperpolarizes rod bipolar
      cells, puffer-applied to the outer plexiform layer. Therefore, it is most likely
      that the spike frequency generated by AII amacrine cells is dependent on the
      excitatory glutamatergic input from rod bipolar cells. Gap junction blockers
      reduced the range of intensity of input with which spike frequency varies.
      Application of TTX to the soma and the proximal dendrite of AII amacrine cells
      blocked the voltage-gated Na(+) current significantly more than application to
      the arboreal dendrite, indicating that the Na(+) channels are mainly localized in
      these regions. Our results suggest that the intensity of the glutamatergic input
      from rod bipolar cells is coded by the spike frequency at the soma and the
      proximal dendrite of AII amacrine cells, raising the possibility that the spikes
      could contribute to the OFF pathway to enhance release of neurotransmitter.

PMID- 17552994
TI  - Properties of paired-pulse firing thresholds and the relationship with paired
      pulse plasticity in hippocampal CA3-CA1 synapses.
AB  - A large variability of paired-pulse plasticity (PPP) has been reported in CA3-CA1
      synapses, and paired-pulse facilitation (PPF) has long been extensively used as a
      relative index of release probability (P(r)) from the presynaptic terminal. One
      of the most common ways of studying P(r) and PPP is to pass paired-pulse
      stimulation (PPS) through an electrode to fire an action potential (AP), which in
      turn opens Ca(2+) channels in the presynaptic boutons to evoke transmitter
      release. However, when the postsynaptic responses were elicited by electrical
      stimulations, the presynaptic APs were usually not monitored. The reliability of
      presynaptic activation, the difference of AP firing thresholds between the first
      and the second pulses of PPS, and its relationship with P(r) and PPP have been
      largely ignored. Here we show that the AP firing thresholds in the same CA3
      pyramidal cells (axons) are obviously lower for the second pulses of the PPS than
      for the first pulses. When single (or small numbers of) presynaptic axons were
      stimulated by low-intensity PPS, a large variation in the postsynaptic response
      probability of the first pulses (P(res1)) and PPP was observed. Increasing
      stimulation intensities resulted in the conversion of a lower P(res1) and PPF to
      a higher P(res1) and paired-pulse depression. These results indicate that changes
      in the reliability of AP initiation by the first pulse of the PPS may account for
      the high variability of P(res1) and PPP observed in CA1 pyramidal cells of the
      hippocampus, therefore PPF may not be a reliable index of P(r) .

PMID- 17552995
TI  - Group I metabotropic glutamate receptors enable two distinct forms of long-term
      depression in the rat dentate gyrus in vivo.
AB  - The existence of long-term depression (LTD) in the dentate gyrus of freely moving
      rats, as well as the contribution of different types of metabotropic glutamate
      receptors (mGluRs) to this form of plasticity, has been the subject of much
      debate. Here, we describe two distinct forms of mGluR-dependent hippocampal LTD
      in the dentate gyrus of freely moving adult rats. LTD, induced by low-frequency
      stimulation (LFS) of the medial perforant path (LFS-LTD), was prevented by
      antagonism of the phospholipase C-coupled receptors, mGluR1 but not mGluR5.
      Chemical LTD, induced by intracerebral application of the group I mGluR agonist
      (R,S)-3,5-dihydroxyphenylglycine, was blocked by antagonism of both mGluR5 and
      mGluR1. Selective activation of mGluR5, using (R,S)-2-chloro-5
      hydroxyphenylglycine (CHPG), also led to chemical LTD. To test whether LFS-LTD
      and chemical LTD share common induction mechanisms, we applied LFS following the
      induction of chemical LTD by CHPG (CHPG-LTD). Surprisingly, LFS impaired CHPG
      LTD. Further analysis revealed that induction of CHPG-LTD led to altered calcium
      dynamics sufficient for its reversal by LFS. We found that LTD induced by (R,S)
      3,5-dihydroxyphenylglycine, but not by CHPG, is impaired by N-methyl-d-aspartate
      receptor antagonism. Both forms of chemical LTD strongly require calcium influx
      through L-type voltage-gated calcium channels. This contrasts with previous
      findings that LFS-LTD in the dentate gyrus is both N-methyl-d-aspartate receptor
      and voltage-gated calcium channel independent. LFS-LTD and LTD induced by group I
      mGluR agonists thus appear to comprise distinct forms of LTD that require the
      activation of specific group I mGluRs and recruit calcium from different sources.

PMID- 17552996
TI  - Small-world network topology of hippocampal neuronal network is lost, in an in
      vitro glutamate injury model of epilepsy.
AB  - Neuronal network topologies and connectivity patterns were explored in control
      and glutamate-injured hippocampal neuronal networks, cultured on planar
      multielectrode arrays. Spontaneous activity was characterized by brief episodes
      of synchronous firing at many sites in the array (network bursts). During such
      assembly activity, maximum numbers of neurons are known to interact in the
      network. After brief glutamate exposure followed by recovery, neuronal networks
      became hypersynchronous and fired network bursts at higher frequency.
      Connectivity maps were constructed to understand how neurons communicate during a
      network burst. These maps were obtained by analysing the spike trains using cross
      covariance analysis and graph theory methods. Analysis of degree distribution,
      which is a measure of direct connections between electrodes in a neuronal
      network, showed exponential and Gaussian distributions in control and glutamate
      injured networks, respectively. Although both the networks showed random
      features, small-world properties in these networks were different. These results
      suggest that functional two-dimensional neuronal networks in vitro are not scale
      free. After brief exposure to glutamate, normal hippocampal neuronal networks
      became hyperexcitable and fired a larger number of network bursts with altered
      network topology. The small-world network property was lost and this was
      accompanied by a change from an exponential to a Gaussian network.

PMID- 17552997
TI  - Reorganization of GABAergic circuits maintains GABAA receptor-mediated
      transmission onto CA1 interneurons in alpha1-subunit-null mice.
AB  - The majority of hippocampal interneurons strongly express GABA(A) receptors
      containing the alpha1 subunit, suggesting that inhibitory control of interneurons
      is important for proper function of hippocampal circuits. Here, we investigated
      with immunohistochemical and electrophysiological techniques how these GABA(A)
      receptors are replaced in mice carrying a targeted deletion of the alpha1-subunit
      gene (alpha1(0/0) mice). Using markers of five major populations of CA1
      interneurons (parvalbumin, calretinin, calbindin, neuropeptide Y and
      somatostatin), we show that these interneurons remain unaffected in alpha1(0/0)
      mice. In triple immunofluorescence staining experiments combining these markers
      with the GABA(A) receptor alpha1, alpha2 or alpha3 subunit and gephyrin, we
      demonstrate a strong increase in alpha3- and alpha2-GABA(A) receptors clustered
      at postsynaptic sites along with gephyrin in most CA1 interneurons in alpha1(0/0)
      mice. The changes were cell type-specific and resulted in an increased number of
      GABAergic synapses on interneurons. These adjustments were mirrored functionally
      by retention of spontaneous IPSCs with prolonged decay kinetics, as shown by
      whole-cell patch-clamp recordings of CA1 interneurons. However, a significant
      decrease in frequency and amplitude of miniature IPSCs was evident, suggesting
      reduced affinity of postsynaptic receptors and/or impaired vesicular GABA
      release. Finally, to assess whether these compensatory changes are sufficient to
      protect against a pathological challenge, we tested the susceptibility of
      alpha1(0/0) mice against kainic acid-induced excitotoxicity. No genotype
      difference was observed in the effects of kainic acid, indicating that the
      absence of a major GABA(A) receptor subtype is functionally compensated for in
      hippocampal interneurons by a reorganization of inhibitory circuits.

PMID- 17552998
TI  - Long-term reduction of brain-derived neurotrophic factor levels and signaling
      impairment following prenatal treatment with the cannabinoid receptor 1 receptor
      agonist (R)-(+)-[2,3-dihydro-5-methyl-3-(4-morpholinyl-methyl) pyrrolo[1,2,3-de]
      1,4-benzoxazin-6-yl]-1- naphthalenylmethanone.
AB  - It is well accepted that adverse life events occurring early in development may
      alter the correct program of brain maturation leading to enhanced vulnerability
      to neuropsychiatric disorders. It has recently been demonstrated that prenatal
      exposure to the cannabinoid receptor 1 agonist (R)-(+)-[2,3-dihydro-5-methyl-3-(4
      morpholinyl-methyl)pyrrolo[1,2,3-de]-1,4-benzoxazin-6-yl]-1-naphthalenylmethanone
      (WIN 55,212-2) produces memory deficit in adulthood, an effect associated with a
      reduced functionality of the glutamatergic system. The aim of our study was to
      identify molecular changes produced by prenatal exposure to WIN 55,212-2 that
      might contribute to late disruption in synaptic plasticity and cognition. For
      this purpose, WIN 55,212-2 was injected in pregnant wistar rats from gestation
      day 5 to 20 and a detailed analysis of the levels of the neurotrophin brain
      derived neurotrophic factor (BDNF) as well as of the signaling molecules
      extracellular signal-regulated kinase (ERK)1/2 and alpha-calcium/calmodulin
      dependent protein kinase II (alpha-CaMKII) was carried out in adult offspring. We
      found that exposure to WIN 55,212-2 significantly reduced BDNF levels in
      hippocampus and frontal cortex. This effect was associated with decreased
      activation of pathways linked to neurotrophin and glutamate receptor signaling.
      In particular, prenatal cannabinoid treatment reduced the phosphorylated levels
      of ERK1/2 in selected subcellular compartments of hippocampus, frontal and
      prefrontal cortex, whereas no changes were observed in the total levels of these
      proteins. Furthermore, a robust reduction of total and phospho-alpha-CaMKII was
      found in the hippocampus of rats prenatally exposed to WIN 55,212-2. In summary,
      the present data suggest that deficits of BDNF levels and signaling through
      ERK1/2 and alpha-CaMKII might contribute to cognitive and neuroplastic defects
      associated with prenatal exposure to cannabinoids.

PMID- 17552999
TI  - Individual differences in the effects of chronic prazosin hydrochloride treatment
      on hippocampal mineralocorticoid and glucocorticoid receptors.
AB  - The aim of this study was to investigate the noradrenergic regulation of
      mineralocorticoid receptors (MRs) and glucocorticoid receptors (GRs) in high
      responder (HR) and low responder (LR) male rats, an animal model of individual
      differences in hypothalamo-pituitary-adrenal axis activity and vulnerability to
      drugs of abuse. The effects of a chronic treatment with the noradrenergic
      alpha(1) antagonist (1-[4-amino-6,7-dimethoxy-2-quinazolinyl]-4-[2
      furanylcarbonyl] piperazine) hydrochloride (prazosin) (0.5 mg/kg, i.p., 35 days)
      were assessed on stress-induced corticosterone (CORT) secretion and on
      hippocampal MRs and GRs in adrenally intact rats. In order to ascertain whether
      the effects of chronic prazosin treatment on hippocampal MRs and GRs were direct
      or indirect, through prazosin-induced CORT secretion, we also assessed the
      effects of the same treatment on adrenalectomized rats with CORT substitutive
      therapy. When compared with LR rats, HR rats exhibited a delayed return to the
      basal level of CORT following acute restraint stress; this was associated with a
      lower binding of MRs and GRs in HR rats than in LR rats. Chronic prazosin
      treatment had no effect in HR animals but markedly reduced hippocampal MRs and
      GRs, and increased stress-induced CORT secretion in LR rats. In LR
      adrenalectomized rats, prazosin reduced hipppocampal MRs but did not change GRs.
      Our results provide evidence of a differential regulation by noradrenaline of
      hippocampal MRs and GRs in HR and LR rats. These data could have clinical
      implications in terms of individual differences in the resistance to
      antidepressant treatments and individual differences in drug abuse.

PMID- 17553000
TI  - Expression and localization of P2 nucleotide receptor subtypes during development
      of the lateral ventricular choroid plexus of the rat.
AB  - The choroid plexuses secrete cerebrospinal fluid (CSF) and regulate the brain's
      internal environment via the blood-CSF barrier. The permeability properties of
      the blood-CSF interface have been studied previously in adult and immature
      brains, however, little is known about the development of CSF secretion and its
      modulation. ATP influences secretion in other epithelia via ionotropic P2X or
      metabotropic P2Y receptors. P2 receptors have frequently been found to be down
      regulated in the postnatal period, suggesting a developmental role for purinergic
      and pyrimidine signalling. The present study investigated the expression of P2
      receptors in lateral ventricular choroid plexus in relation to recent studies of
      aquaporin-1 expression and rapid expansion of the lateral ventricles in rat
      embryos. In the present study mRNAs for all known mammalian nucleotide receptor
      subtypes, except P2X(7), were identified from as early as E15. P2X(7) mRNA was
      detected from E18. Indications of differential expression patterns were observed
      for the different subtypes during development: an apparent increase in expression
      for P2Y(2) and P2X(7), a decline in P2X(1-2,4), no detectable difference in
      expression levels for P2X(6) and P2Y(12-13) and transient expression peaks for
      P2X(3,5) and P2Y(1,4,6,14). P2X(4,5,7) and P2Y(1,4) receptor proteins were
      detected immunohistochemically in the choroidal epithelium from early in
      development (E15 or E18). Their differing developmental profiles suggest specific
      roles in the development of CSF secretion that may have particular relevance for
      the rapid expansion of the ventricles that occurs in the embryo. P2X(5) and
      P2Y(6) were also detected in the developing neuropendyma from P0 and P9,
      respectively.

PMID- 17553001
TI  - Expression of the cGMP-specific phosphodiesterases 2 and 9 in normal and
      Alzheimer's disease human brains.
AB  - We studied the mRNA expression of cGMP-hydrolysing phosphodiesterases (PDEs) in
      selected brain areas of normal elderly people and patients with Alzheimer's
      disease. Using radioactive in-situ hybridization histochemistry we found a
      widespread distribution of the mRNA for PDE2 and PDE9, whereas no specific
      hybridization signal was observed for PDE5. We observed PDE2 and PDE9 mRNA in all
      cortical areas studied (insular cortex, entorhinal cortex and visual cortex),
      although to a different extent. PDE2 mRNA was high in the claustrum, whereas PDE9
      mRNA was moderate. PDE2 and PDE9 mRNAs was present in the putamen. No cGMP
      hydrolysing PDE expression was observed in the globus pallidus. PDE2 and PDE9
      mRNA was observed in all subareas of the hippocampus; however, there were
      significant differences in the amount of expression. In the Purkinje and
      cerebellar granule cells only PDE9 expression was observed. PDE2 and PDE9 mRNA
      expression was not significantly different in Alzheimer's disease brains.

PMID- 17553002
TI  - Two faces of calcium activation after optic nerve trauma: life or death of
      retinal ganglion cells in vivo depends on calcium dynamics.
AB  - Calcium elevations after neurotrauma are not only implicated in cell death but
      may contribute to adaptive plasticity. We now wished to resolve this
      contradiction by following calcium dynamics after optic nerve crush in vivo.
      Adult rats received no injury (n = 5), unilateral mild (n = 10) or moderate optic
      nerve crush (n = 10) (ONC), or axotomy (n = 5). Before surgery, retinal ganglion
      cells (RGCs) were retrogradely labelled with Oregon Green BAPTA-dextran, a
      fluorescent calcium marker. Calcium-related fluorescence intensity (FI) was
      repeatedly measured in individual RGCs in vivo using the in vivo confocal
      neuroimaging (ICON) method. Four different RGC types were found. Normal RGCs
      without FI change were found in sham rats and also in both ONC groups. RGCs with
      mild damage were seen only after mild ONC, showing an initial calcium depression
      of 26% at day 4 followed by a 169% increase 15 days after ONC. RGCs with moderate
      damage were found only after moderate ONC and showed calcium hypoactivation
      followed by a slower return toward baseline and a delayed calcium increase of 72%
      above baseline. Sixty to sixty-five per cent of the RGCs in both ONC groups and
      all RGCs in the axotomy group died within 6 days following a fast and massive
      calcium increase of 316% with a concomitant 156% soma size increase. In
      conclusion rapid calcium elevation leads to cell death, while an initial calcium
      depression followed by a delayed and moderate calcium hyperactivation is
      associated with cell survival. We propose that immediate, massive calcium
      activation is maladaptive whereas delayed and moderate hyperactivation of
      surviving cells is adaptive. Implications for pharmacotherapy are discussed.

PMID- 17553003
TI  - Mechanism of spontaneous and self-sustained oscillations in networks connected
      through axo-axonal gap junctions.
AB  - Electrical coupling of clusters of neurons via axo-axonal gap junctions is a
      candidate mechanism underlying the ultra-fast (> 100 Hz) oscillations recorded in
      various in vitro and in vivo normal and pathological conditions [Traub et al.
      (1999)Neuroscience, 92, 407-426]. The poor characterization of axo-axonal gap
      junctions, however, limits experimental verification of this mechanism. We
      simulated networks of prototype multi-compartmental neurons in order to identify
      the parameters constraining the production and frequency of ultra-fast
      oscillations. Weak axo-axonal coupling was found to synchronize networks
      preferentially at the gamma-range frequency (30-100 Hz). Networks with strong axo
      axonal coupling were able to produce 200 Hz oscillations, a finding we extended
      with several new observations. Ultra-fast oscillations arose spontaneously during
      dendritic excitation, i.e. in the absence of extrinsic axonal background spikes,
      as the spike trigger zone concomitantly shifted from soma to axon. The all-or
      none oscillations could be transitory or self-sustained, and lasted longer in
      larger networks. They occurred more likely during low to modest soma firing
      rates, as strong afterhyperpolarizing currents tended to impair them. The rate of
      the rhythm was independent of network size and of the level of excitation, but
      inversely proportional to the distance of the junctions from the soma. As a
      matter of fact, the resulting axonal firing rate was the highest one at which
      antidromic spikes would not collide with spikes reflected from the soma. Taken
      together, the observed model dynamics lends further credibility to axo-axonal
      coupling as a mechanism of ultra-fast oscillations.

PMID- 17553004
TI  - Casein kinase I epsilon gene transfer into the suprachiasmatic nucleus via
      electroporation lengthens circadian periods of tau mutant hamsters.
AB  - Circadian activity rhythms in mammals are controlled by the expression and
      transcriptional regulation of clock genes in the suprachiasmatic nucleus (SCN).
      The circadian cycle length in hamsters is regulated in part by casein kinase I
      epsilon (CKIepsilon). A semidominant mutation (C-->T, R178C, CKIepsilon(tau))
      appears to act as a dominant-negative allele to shorten the period of circadian
      rhythms. We tested this hypothesis in vivo by expressing wild-type CKIepsilon
      gene in homozygous tau mutant hamsters. High-level CKIepsilon(+/+) gene transfer
      and expression (as indicated by green fluorescent protein) were obtained by
      injecting CKIepsilon-containing plasmids bilaterally near the SCN, followed by in
      vivo electroporation. Rhythmicity reappeared 5-7 days after electroporation, with
      a gradual increase in circadian period over the next 10 days. The circadian
      period returned to the baseline over the next 20 days. For the five hamsters with
      clearest gene expression in the SCN, the mean lengthening time was 39.6 min.
      Period change was not observed in either control tau mutant hamsters
      electroporated with plasmids lacking the CKIepsilon gene or in wild-type hamsters
      with plasmids containing the wild-type CKIepsilon gene. Therefore, normal
      periodicity in homozygous CKIepsilon(tau) hamsters was partially rescued by
      expression of the wild-type CKIepsilon gene in the SCN, supporting a competitive
      and dominant-negative action of the mutant allele. This study shows that
      electroporation of wild-type CKIepsilon gene into the SCN is sufficient for
      lengthening the shorter circadian period of tau mutant hamsters in a time
      dependent way and supports the conclusion that CKIepsilon(tau) is the cause of
      the shorter period.

PMID- 17553005
TI  - Brainstem cholinergic modulation of muscle tone in infant rats.
AB  - In week-old rats, lesions of the dorsolateral pontine tegmentum (DLPT) and
      nucleus pontis oralis (PnO) have opposing effects on nuchal muscle tone.
      Specifically, pups with DLPT lesions exhibit prolonged bouts of nuchal muscle
      atonia (indicative of sleep) and pups with PnO lesions exhibit prolonged bouts of
      high nuchal muscle tone (indicative of wakefulness). Here we test the hypothesis
      that nuchal muscle tone is modulated, at least in part, by cholinergically
      mediated interactions between these two regions. First, in unanesthetized pups,
      we found that chemical infusion of the cholinergic agonist carbachol (22 mm, 0.1
      microL) within the DLPT produced high muscle tone. Next, chemical lesions of the
      PnO were used to produce a chronic state of high nuchal muscle tone, at which
      time the cholinergic antagonist scopolamine (10 mm, 0.1 microL) was infused into
      the DLPT. Scopolamine effectively decreased nuchal muscle tone, thus suggesting
      that lesions of the PnO increase muscle tone via cholinergic activation of the
      DLPT. Using 2-deoxyglucose autoradiography, metabolic activation throughout the
      DLPT was observed after PnO lesions. Finally, consistent with the hypothesis that
      PnO inactivation produces high muscle tone, infusion of the sodium channel
      blocker lidocaine (2%) into the PnO of unanesthetized pups produced rapid
      increases in muscle tone. We conclude that, even early in infancy, the DLPT is
      critically involved in the regulation of muscle tone and behavioral state, and
      that its activity is modulated by a cholinergic mechanism that is directly or
      indirectly controlled by the PnO.

PMID- 17553006
TI  - Disruption of reelin signaling attenuates methamphetamine-induced
      hyperlocomotion.
AB  - To clarify whether reelin signaling is involved in dopaminergic neurotransmission
      in the adult mouse brain, we investigated dopamine function in mice lacking
      reelin (reeler). We found that methamphetamine-induced locomotor activity is
      significantly attenuated in reeler mice. To elucidate the mechanism of this
      phenomenon, we first investigated presynaptic dopamine release; however, there
      were no significant differences in wildtype, heterozygous reeler and homozygous
      reeler mice. Next, we examined the locomotor response to intra-accumbens
      injection of dopamine D1 and D2 receptor agonists, and found that lack of reelin
      signaling results in decreases in both D1 and D2 receptor-mediated dopaminergic
      functions. In addition, we measured dopamine receptor binding in the striatum,
      and found that both D1 and D2 classes of dopamine receptors are reduced in reeler
      mice. Furthermore, we found that the phosphorylation levels of DARPP-32 are also
      changed by lack of reelin signaling. Finally, to distinguish between a
      developmental role of reelin or an acute role of reelin in adult mouse, we
      intraventricularly infused CR-50, a monoclonal antibody against reelin.
      Interestingly, infusion of CR-50 also significantly reduced methamphetamine
      induced hyperlocomotion in wildtype mice, showing that reelin has an acute role
      in the dopaminergic system. These results indicate that reelin signaling plays a
      pivotal role in the dopaminergic system in adult mice, especially in postsynaptic
      levels.

PMID- 17553007
TI  - Differential activation of CRF receptor subtypes removes stress-induced memory
      deficit and anxiety.
AB  - The objective of this study was to investigate the role of corticotropin
      releasing factor receptors 1 (CRF(1)) and 2 (CRF(2)) in anxiety-like behavior and
      learning of C57BL/6J mice after exposure to a stressful stimulus. When C57BL/6J
      mice were exposed to immobilization (1 h) serving as stressful stimulus, context-
      and tone-dependent fear conditioning were impaired if the training followed
      immediately after immobilization. The stress-induced impairment of context
      dependent fear conditioning was prevented by specific blockade of CRF(2) of the
      lateral septum (LS) with anti-sauvagine-30. Immobilization did not only affect
      conditioned fear, but also enhanced, through CRF(2) of the LS, anxiety-like
      behavior determined with the elevated plus maze. Recovery from stress-induced
      anxiety and impairment of context-dependent fear conditioning was observed after
      1 h delay of training and required hippocampal CRF(1), as indicated by the
      finding that this recovery was prevented by blockade of intrahippocampal CRF(1).
      It was concluded that exposure to a stressor initially affected both anxiety-like
      behavior and contextual conditioned fear through septal CRF(2), while the later
      activation of hippocampal CRF(1) resulted in the return to baseline levels of
      both processes. Intraventricular injection of mouse urocortin 2, a CRF(2)
      selective agonist, removed the stress-induced anxiety and learning impairment,
      but did not reduce the activation of the hypothalamic pituitary adrenal axis
      indicative of the hormonal stress response. We propose that the enhanced anxiety
      is the component of the stress response responsible for the memory deficit.

PMID- 17553008
TI  - Decreased motivation to eat in mu-opioid receptor-deficient mice.
AB  - Altered motivational processes might participate to the physiopathology of eating
      related disorders. The endogenous opioid system is thought to mediate the hedonic
      properties of food intake. To assess the role for the micro-opioid receptor (MOR)
      pathway in the motivational properties of food intake, in the present study we
      tested wild-type and MOR-deficient mice (MOR-/-) in a nose-poke operant paradigm
      for chow or sucrose pellets. To avoid confounding factors linked to food
      restriction/deprivation experience, mice were always provided with food ad
      libitum. Although less MOR-/- than wild-type mice initiated operant behaviour,
      under a fixed ratio-1 (FR-1) reinforcement schedule the two genotypes showed
      similar patterns of food-driven nose-poking, indicating preserved cognitive
      abilities in MOR-deficient mice. However, during FR-3 and progressive ratio (PR)
      reinforcement experiments, MOR-/- mice showed lower levels of nose-poking for
      either chow or sucrose pellets than wild-type mice, indicating a crucial role for
      the MOR pathway in the motivational properties of food intake. Moreover, under
      the PR reinforcement schedule mice nose-poking for sucrose pellets showed higher
      genotype-independent breakpoint levels than mice working for chow pellets,
      indicating that the MOR pathway is not essential for hedonic processing of
      palatable food intake. Finally, MOR-/- mice did not differ from wild-type mice in
      the rate of operant responding extinction, further supporting the notion of
      unaltered cognitive abilities in the MOR-deficient mice. The present findings
      strongly indicate that the MOR pathway mediates the motivational properties of
      food intake, but it is not essential for hedonic processing of ingestive
      behaviour.

PMID- 17553010
TI  - Role of cortical cannabinoid CB1 receptor in conditioned taste aversion memory.
AB  - The brain endocannabinoid system has been shown to play a role in memory, though
      the extent to which this role generalizes over different types and processes of
      memory is not yet determined. Here we show that the cannabinoid receptor 1 (CB1)
      plays differential roles in acquisition, extinction and reconsolidation of
      conditioned taste aversion (CTA) memory in the rat insular cortex, which contains
      the taste cortex. Activation of the CB1 receptor in the insular cortex inhibits
      acquisition and reconsolidation but not extinction, whereas blockade of the CB1
      receptor promotes memory and blocks extinction of CTA, while having no apparent
      effect on reconsolidation. The CB1 ligands used in this study were incapable of
      substituting the unconditioned stimulus in CTA training. All in all, the data
      raise the possibility that the state of activity of the CB1 receptor in the
      insular cortex contributes to the encoding of hedonic valence that enters into
      association with taste items.

PMID- 17553009
TI  - Role of the midbrain dopaminergic system in modulation of vocal brain activation
      by social context.
AB  - In a well-studied model of social behaviour, male zebra finches sing directed
      song to court females and undirected song, used possibly for practice or
      advertisement. Although the two song types are similar, the level of neural
      activity and expression of the immediate early gene egr-1 are higher during
      undirected than during directed singing in the lateral part of the basal ganglia
      song nucleus AreaX (LAreaX) and its efferent pallial song nuclei lateral
      magnocellular nucleus of the anterior nidopallium (LMAN) and the robust nucleus
      of the arcopallium (RA). As social interactions are dependent on brain motivation
      systems, here we test the hypothesis that the midbrain ventral tegmental area
      substantia nigra pars compacta (VTA-SNc) complex, which provides a strong
      dopaminergic input to LAreaX, is a source of this modulation. Using egr-1
      expression, we show that GABAergic interneurons in VTA-SNc are more active during
      directed courtship singing than during undirected singing. We also found that
      unilateral removal of VTA-SNc input reduced singing-dependent gene expression in
      ipsilateral LAreaX during both social contexts but it did not eliminate social
      context differences in LAreaX. In contrast, such lesions reduced and eliminated
      the social context differences in efferent nuclei LMAN and RA, respectively.
      These results suggest that VTA-SNc is not solely responsible for the social
      context gene regulation in LAreaX, but that VTA-SNc input to LAreaX enhances the
      singing-regulated gene expression in this nucleus and, either through LAreaX or
      through direct projections to LMAN and RA, VTA-SNc is necessary for context
      dependent gene regulation in these efferent nuclei.

PMID- 17553011
TI  - Disgust sensitivity predicts the insula and pallidal response to pictures of
      disgusting foods.
AB  - The anterior insula has been implicated in coding disgust from facial, pictorial
      and olfactory cues, and in the experience of this emotion. Personality research
      has shown considerable variation in individuals' trait propensity to experience
      disgust ('disgust sensitivity'). Our study explored the neural expression of this
      trait, and demonstrates that individual variation in disgust sensitivity is
      significantly correlated with participants' ventroanterior insular response to
      viewing pictures of disgusting, but not appetizing or bland, foods. Similar
      correlations were also seen in the pallidum and orofacial regions of motor and
      somatosensory cortices. Our results also accord with comparative research showing
      an anterior to posterior gradient in the rat pallidum reflecting increased
      'liking' of foods [Smith, K. S. and Berridge, K. C. (2005) J. Neurosci., 25, 849
      8637].

PMID- 17553012
TI  - Layer and frequency dependencies of phase response properties of pyramidal
      neurons in rat motor cortex.
AB  - It is postulated that synchronous firing of cortical neurons plays an active role
      in cognitive functions of the brain. An important issue is whether pyramidal
      neurons in different cortical layers exhibit similar tendencies to synchronise.
      To address this issue, we performed intracellular and whole-cell recordings of
      regular-spiking pyramidal neurons in slice preparations of the rat motor cortex
      (18-45 days old) and analysed the phase response curves of these pyramidal
      neurons in layers 2/3 and 5. The phase response curve represents how an external
      stimulus affects the timing of spikes immediately after the stimulus in
      repetitively firing neurons. The phase response curve can be classified into two
      categories, type 1 (the spike is always advanced) and type 2 (the spike is
      advanced or delayed depending on the stimulus phase), and are important
      determinants of whether or not rhythmic synchronization of neuron pairs occurs.
      We found that pyramidal neurons in layer 2/3 tend to display type-2 phase
      response curves whereas those in layer 5 tend to exhibit type-1 phase response
      curves. The differences were prominent particularly in the gamma-frequency range
      (20-45 Hz). Our results imply that the layer-2/3 pyramidal neurons, when coupled
      mutually through fast excitatory synapses, may exhibit a much stronger tendency
      for rhythmic synchronization than layer-5 neurons in the gamma-frequency range.

PMID- 17553013
TI  - No improvement by amphetamine on learned non-use, attempts, success or movement
      in skilled reaching by the rat after motor cortex stroke.
AB  - Amphetamine (AMPH) has been proposed as a treatment for post-stroke motor
      deficits when coupled with symptom-relevant physical rehabilitation. Whereas a
      number of experimental studies report improvements in endpoint measures of
      skilled reaching for food by rats, there has been no assessment of whether
      beneficial effects extend to overcoming learned non-use of the limb in the acute
      post-stroke period or to the qualitative deficits in movement in the chronic post
      stroke period. In addition to evaluating the effects of AMPH on success, these
      were the objectives of the present study. In three different reaching
      experiments, groups of rats were pre-trained in skilled reaching for food prior
      to receiving a motor cortex stroke via pial removal. Postoperatively the rats
      received periodic AMPH treatment and daily rehabilitation. In the acute post
      stroke period, AMPH failed to prevent the development of learned non-use of the
      limb, and in the acute and chronic period failed to improve recovery of reaching
      success, and also failed to improve the qualitative aspects of reaching
      movements. Nevertheless, AMPH did enhance adjunct non-reaching movements of
      locomotion, rearing and turning. The results are discussed in relation to the
      idea that the beneficial effects of post-stroke AMPH treatment do not extend to
      all movements, especially the movements of a forelimb in retrieving and consuming
      food.

PMID- 17553014
TI  - Endurance exercise facilitates relearning of forelimb motor skill after focal
      ischemia.
AB  - Endurance exercise (i.e. running), by up-regulating brain-derived neurotrophic
      factor (BDNF) and other modulators of synaptic plasticity, improves attention and
      learning, both critical components of stroke rehabilitation. We hypothesized
      that, following middle cerebral artery occlusion in male Sprague-Dawley rats,
      endurance exercise would act synergistically with a challenging skilled forelimb
      task to facilitate motor recovery. Animals were randomly assigned to one of four
      rehabilitation conditions: no rehabilitation, running only, reach training only,
      and reach training preceded by running (run/reach training) for 5 weeks beginning
      5 days after stroke. The behavioral outcome, morphological change and mRNA
      expression of proteins implicated in neuroplasticity (BDNF, synapsin I and
      microtubule-associated protein 2) were compared. Endurance exercise on a
      motorized running wheel, prior to reach training, enhanced recovery of skilled
      reaching ability but did not transfer to gross motor skills such as postural
      support (forelimb asymmetry test) and gait (ladder rung walking test).
      Microtubule-associated protein 2 staining density in the run/reach group was
      slightly enhanced in the contralateral motor cortex compared with the
      contralateral sensory and ipsilateral cingulate cortices, suggesting that running
      preceding reach training may have resulted in more dendritic branching within the
      motor cortex in this group. No significant differences in mRNA levels were
      detected among the training paradigms; however, there was a trend toward greater
      BDNF and synapsin I mRNA in the reaching groups. These findings suggest that
      exercise facilitates learning of subsequent challenging reaching tasks after
      stroke, which has the potential to optimize outcomes in patients with stroke.

PMID- 17553015
TI  - Homeostatic plasticity in human motor cortex demonstrated by two consecutive
      sessions of paired associative stimulation.
AB  - Long-term potentiation (LTP) and long-term depression (LTD) underlie most models
      of learning and memory, but neural activity would grow or shrink in an
      uncontrolled manner, if not guarded by stabilizing mechanisms. The Bienenstock
      Cooper-Munro (BCM) rule proposes a sliding threshold for LTP/LTD induction: LTP
      induction becomes more difficult if neural activity was high previously. Here we
      tested if this form of homeostatic plasticity applies to the human motor cortex
      (M1) in vivo by examining the interactions between two consecutive sessions of
      paired associative stimulation (PAS). PAS consisted of repeated pairs of
      electrical stimulation of the right median nerve followed by transcranial
      magnetic stimulation of the left M1. The first PAS session employed an
      interstimulus interval equalling the individual N20-latency of the median nerve
      somatosensory-evoked cortical potential plus 2 ms, N20-latency minus 5 ms, or a
      random alternation between these intervals, to induce an LTP-like increase in
      motor-evoked potential (MEP) amplitudes in the right abductor pollicis brevis
      muscle (PAS(LTP)), an LTD-like decrease (PAS(LTD)), or no change (PAS(Control)),
      respectively. The second PAS session 30 min later was always PAS(LTP). It induced
      an moderate LTP-like effect if conditioned by PAS(Control), which increased if
      conditioned by PAS(LTD), but decreased if conditioned by PAS(LTP). Effects on MEP
      amplitude induced by the second PAS session exhibited a negative linear
      correlation with those in the first PAS session. Because the two PAS sessions
      activate identical neuronal circuits, we conclude that 'homosynaptic-like'
      homeostatic mechanisms in accord with the BCM rule contribute to regulating
      plasticity in human M1.

PMID- 17553016
TI  - Factors influencing the relation between corticospinal output and muscle force
      during voluntary contractions.
AB  - The mechanisms by which voluntary forces of different strengths are produced in
      human muscles are not clear. We studied the relation between force and surface
      electromyography (sEMG) variables over a wide range of voluntary contraction
      strengths of biceps brachii (BIC) and abductor digiti minimi (ADM). The relation
      between force and motor evoked potentials (MEPs) to transcranial magnetic
      stimulation of motor cortex was also assessed. The root mean square of sEMG and
      median frequency (Mf) of the sEMG power spectrum as well as the MEP area of ADM
      and BIC were calculated up to the maximum voluntary contraction (MVC). The root
      mean square of ADM and BIC increased with increasing force levels up to the MVC.
      The Mf of BIC increased with force levels up to 70% MVC after which it rapidly
      declined. The Mf of ADM peaked at 40% MVC to slowly decline thereafter. The MEP
      changes with force were similar to Mf changes. Thus, corticospinal output, as
      tested by the Mf and MEPs, does not parallel force increments across the
      contraction range. This decline, which is contingent on the relative contribution
      of motor unit recruitment and rate coding to force production in each muscle, may
      depend on reduced motoneurone responsiveness at high firing rates. We suggest
      that, under controlled conditions, the frequency content of the sEMG signal may
      be taken to indicate motor unit recruitment range. This information may improve
      the utility of the Mf to enable evaluation of voluntary activation under
      different conditions.

PMID- 17553017
TI  - Human limb-specific and non-limb-specific brain representations during
      kinesthetic illusory movements of the upper and lower extremities.
AB  - Sensing movements of the upper and lower extremities is important in controlling
      whole-body movements. We have shown that kinesthetic illusory hand movements
      activate motor areas and right-sided fronto-parietal cortices. We investigated
      whether illusions for the upper and lower extremities, i.e. right or left hand or
      foot, activate the somatotopical sections of motor areas, and if an illusion for
      each limb engages the right-sided cortices. We scanned the brain activity of 19
      blindfolded right-handed participants using functional magnetic resonance imaging
      (fMRI) while they experienced an illusion for each limb elicited by vibrating its
      tendon at 110 Hz (ILLUSION). As a control, we applied identical stimuli to the
      skin over a nearby bone, which does not elicit illusions (VIBRATION). The
      illusory movement (ILLUSION vs. VIBRATION) of each immobile limb activated limb
      specific sections of the contralateral motor cortex (along with somatosensory
      area 3a), dorsal premotor cortex (PMD), supplementary motor area (SMA), cingulate
      motor area (CMA), and the ipsilateral cerebellum, which normally participate in
      execution of movements of the corresponding limb. We found complex non-limb
      specific representations in rostral parts of the bilateral SMA and CMA, and
      illusions for all limbs consistently engaged concentrated regions in right-sided
      fronto-parietal cortices and basal ganglia. This study demonstrated complete sets
      of brain representations related to kinesthetic processing of single-joint
      movements of the four human extremities. The kinesthetic function of motor areas
      suggests their importance in somatic perception of limb movement, and the non
      limb-specific representations indicate high-order kinesthetic processing related
      to human somatic perception of one's own body.

PMID- 17553019
TI  - Determinants of antenatal care utilization in three rural areas of Vietnam.
AB  - OBJECTIVE: To identify factors associated with any use of antenatal care (ANC),
      gestational age at entry to ANC, number of visits, and overall ANC utilization in
      the three provinces of Long an, Ben tre, and Quang ngai. DATA: The Vietnam
      Australia Primary Health Care Project conducted cross-sectional surveys in 1998
      1999. Data from 1,335 eligible women were available for analysis. METHODS:
      Explanatory variables were selected using the Andersen Health Seeking Behavior
      Model and analyzed using multivariate regression techniques. RESULTS: External
      environment, predisposing characteristics, and need, which existed before contact
      with ANC providers, were most related to using any ANC and gestational age at
      entry to ANC. However, ANC services provided to women and personal health care
      during pregnancy, which could have resulted from initial contact with ANC
      providers, were most related to continuation of ANC visits and overall ANC
      utilization. Significant variability in the use of ANC existed between provinces
      and between subsets of women in each province. CONCLUSION: To have more women who
      attend ANC and attend early, promotion should be targeted at high-risk groups of
      women. However, to improve the number of ANC visits and overall utilization, the
      quality of ANC services should be improved.

PMID- 17553020
TI  - Association of maternal chronic disease and negative birth outcomes in a non
      Hispanic Black-White Mississippi birth cohort.
AB  - OBJECTIVE: To investigate the impact of selected maternal chronic medical
      conditions, race, and age on preterm birth (PTB), low birth weight (LBW), and
      infant mortality among Mississippi mothers from 1999 to 2003. DESIGN: A
      retrospective cohort analysis of linked birth and death certificates. SAMPLE: The
      1999-2003 Mississippi birth cohort comprising 202,931 singleton infants born to
      African American and White women. MEASUREMENTS: The relationship between maternal
      chronic conditions and the dependent variables of PTB, LBW, and infant mortality
      were investigated using logistic regression analysis. RESULTS: PTB, LBW, and
      infant mortality were more prevalent among African American women, very young
      women (< or =15 years), and women with certain chronic medical conditions. Among
      White mothers, maternal chronic hypertension was significantly associated with
      PTB and LBW, and maternal diabetes with PTB and infant mortality. Among African
      American mothers, maternal cardiac disease was significantly associated with PTB
      and LBW; maternal chronic hypertension was significantly associated with LBW and
      infant mortality; and maternal diabetes with PTB. CONCLUSIONS: Maternal chronic
      hypertension and diabetes were significantly associated with negative birth
      outcomes regardless of maternal race. Maternal cardiac disease was only
      significantly associated with PTB and LBW among African Americans.

PMID- 17553021
TI  - The clinical, psychosocial, and socioeconomic concerns of urban youth living with
      diabetes.
AB  - OBJECTIVE: Young people with chronic diseases face the challenge of moving from
      the pediatric to the adult health care environment, in addition to the normal
      hurdles of young adulthood. To most effectively help them through this process,
      we must first understand their perspective. DESIGN: Qualitative study of the
      social and emotional impact of having diabetes. SAMPLE: Young adults (n=23), aged
      19-26, who had been living with diabetes for a median of 12 years (range 4-19)
      were contacted; all but one were from underserved ethnic minorities.
      MEASUREMENTS: Semistructured telephone interviews were conducted, transcribed,
      and coded. RESULTS: Having diabetes profoundly affected the life choices and
      expectations of these young people; their feelings and attitudes evolved over
      time. Financial and insurance concerns were key, because managing diabetes care
      on one's own as an adult was a major challenge. Most young people reported that
      family, friends, and coworkers were sources of support, but that disclosure of
      their diabetes was problematic. CONCLUSIONS: Offering emotional and practical
      support to young adults coping with diabetes is key to ensuring adequate medical
      management as they move into the adult system and assume full responsibility for
      their health.

PMID- 17553022
TI  - Evaluating the social and economic impact of community-based prenatal care.
AB  - OBJECTIVE: This article describes the evaluation and findings of a community
      based prenatal care program, Omaha Healthy Start (OHS), designed to reduce local
      racial disparities in birth outcomes. DESIGN: This evaluative study used a
      comparative descriptive design, and Targeting Outcomes of Programs was the
      conceptual framework for evaluation. SAMPLE: The evaluation followed 3 groups for
      2 years: OHS birth mothers (N=79; N=157); non-OHS participant birth mothers
      (N=746; N=774); and Douglas County birth mothers (N=7,962; N=7,987). MEASUREMENT:
      OHS provided case management, home visits, screening, referral, transportation,
      and health education to participants. Program outcome measures included low birth
      weight, infant mortality, adequacy of care, trimester of care, and costs of care.
      RESULTS: OHS birth outcomes improved during year 2, and there was a 31% cost
      saving in the average hospital expenditure compared with the nonparticipant
      groups. Preliminary evaluative analysis indicates that prenatal case management
      and community outreach can improve birth outcomes for minority women, while
      producing cost savings. CONCLUSIONS: Further prospective study is needed to
      document trends over a longer period of time regarding the relationship between
      community-based case management programs for minority populations, birth
      outcomes, and costs of care.

PMID- 17553023
TI  - Surveillance of HIV exposure and postexposure prophylaxis among health care
      workers in Greece.
AB  - OBJECTIVE: Many developed countries have implemented surveillance systems for
      monitoring occupational exposure to HIV. The aim of the present study was to
      analyze surveillance data on HIV postexposure prophylaxis (PEP) for health care
      workers (HCWs) in Greece. DESIGN: All data reported to the Hellenic Centre for
      Disease Control and Prevention between January 1996 and June 2005 were analyzed.
      SAMPLE AND MEASUREMENT: 188 reported occupational exposures to HIV were analyzed,
      retrospectively. RESULTS: Most exposures were in the physicians (37.8%), followed
      by the nursing personnel (18.6%). Nearly 38% of the HCWs were males and the
      predominant type of biological material involved in the exposure was blood
      (74.5%). Two drugs were used for PEP in 23.4% of the HCWs, and 3 drugs in 66.5%
      of the reported cases. CONCLUSIONS: Greek guidelines provide guidance for
      treating HCWs after occupational exposure to HIV. In our study, antiretroviral
      treatment, a three-drug regimen in the majority of the cases, was prescribed
      after evaluation of specially appointed physicians. The surveillance system of
      occupational exposure to HIV in HCWs should be further developed and enhanced in
      order to monitor and evaluate the risk factors surrounding the incidents.

PMID- 17553024
TI  - Administrator self-ratings of organization capacity and performance of healthy
      community development projects in Taiwan.
AB  - OBJECTIVE: To examine the relationship between the capacities of various
      community organizations and their performance scores for healthy community
      development. DESIGN: This cross-sectional study was conducted by examining all
      community organizations involved in the Taiwan national healthy community
      development project. SAMPLE: Of 213 administrators contacted, 195 (a return rate
      of 91.6%) completed a self-administered questionnaire between October and
      November 2003. The research instrument was self-developed and based on the
      Donabedian model. It examined the capacity of the community organizations and
      their performance in developing a healthy community. RESULTS: The average overall
      healthy community development performance score was 5.0 on a 7-point semantic
      differential scale, with the structure variable rated as the lowest among the 3
      subscales. Community organization capacities in the areas of funding, resources
      committed, citizen participation, and certain aspects of organizational
      leadership were found to be significantly related to healthy community
      development performance. Each of the regression models showed a different set of
      capacities for the community organization domains and explained between 25% and
      33% of the variance in performance. CONCLUSIONS: The study validates the
      theoretical relationships among the concepts identified in the Donabedian model.
      Nursing interventions tailored to enhance resident citizen participation in order
      to promote community coalitions are strongly supported.

PMID- 17553025
TI  - Increasing the delivery of health care services to migrant farm worker families
      through a community partnership model.
AB  - The Farm Worker Family Health Program (FWFHP) is a 13-year community partnership
      model designed to increase delivery of health care services for migrant farm
      worker families. During a yearly 2-week immersion experience, 90 students and
      faculty members provide health care services, including physical examinations,
      health screenings, health education, physical therapy, and dental care for 1,000
      migrant farm workers and migrant children. Students and faculty members gain a
      deeper appreciation of the health and social issues that migrant farm worker
      families face by providing health care services in the places where migrant
      families live, work, and are educated. Although the model is not unique, it is
      significant because of its sustained history, interdisciplinary collaboration
      among community and academic partners, mutual trust and connections among the
      partners, and the way the program is tailored to meet the needs of the population
      served. The principles of social responsibility and leadership frame the FWFHP
      experience. This community partnership model can be replicated by others working
      with at-risk populations in low-resource settings.

PMID- 17553026
TI  - Cigarette smoking, socioeconomic status, and psychosocial factors: examining a
      conceptual framework.
AB  - Inequalities in cigarette smoking prevalence exist, with smokers more likely to
      be poor and less educated. Higher socioeconomic status (SES) is associated with
      higher quit rates. The overall relationship between low SES and poor health, as
      measured by morbidity and mortality, is well established. However, research
      indicates that inequalities in health are not explained by SES alone; other
      variables, such as psychosocial factors, may play a significant role. Williams
      has developed a conceptual framework to examine relationships among SES,
      psychosocial factors, and medical care related to health outcomes. According to
      Williams, the interrelationships among these factors have yet to be determined.
      As such, the pathways among the variables within psychosocial factors are
      explored and the authors discuss application to public health nursing practice
      and areas for future research. Further understanding of these relationships in
      the context of smoking may inform prevention and cessation strategies.

PMID- 17553027
TI  - Development of a Family Dynamic Environment Scale for Korean adolescents.
AB  - The objective of this study was to develop a short and reliable Family Dynamic
      Environment Scale (FDES) that would better serve the needs of mental health
      professionals in detecting the potential for delinquent behavior in Korean
      adolescents related to a dysfunctional family dynamic environment. Semi
      structured interviews with 30 adolescents were initially conducted to generate a
      set of items, after which, 44 participants were included in method test-retest
      reliability test. Finally, 544 participants recruited by proportional stratified
      random sampling were included in a factor analysis. The original version of the
      FDES had 60 items in 7 categories; the final version included 42 items grouped
      into 5 factors. Both test-retest reliability and Cronbach's alpha coefficient
      were high for the final version of the scale. As a result of factor analysis,
      five factors were extracted: family psychological climate, parent-child
      relationship, paternal parenting attitude, family cohesion, and maternal
      parenting attitude. These contributed 50.3% of the variance in the item scores.
      All 42 items loaded above .35 on their respective factors. The Cronbach's alpha
      coefficients for internal consistency were .95 for the total 42 items and .92,
      .81, .82, .78, and .71, respectively, for each of the 5 factors.

PMID- 17553028
TI  - Nursing the community, a look back at the 1984 dialogue between Virginia A.
      Henderson and Sherry L. Shamansky.
AB  - Dr. Sherry L. Shamansky, one of the founding editors of Public Health Nursing,
      interviewed renowned 20th-century leader, Virginia Avenal Henderson (1897-1996),
      then research associate emeritus at Yale University School of Nursing, about the
      nursing of "aggregates." Their discussion, originally published in Public Health
      Nursing, in 1984 (Vol. 1, No. 4), highlights Henderson's views about the scope of
      nursing, health care organization and funding, and perceived tension between
      direct care of the sick in the community and preventive activities directed
      toward communities or populations at risk. Readers familiar with Henderson's
      influential definition of nursing may find her responses to interview questions
      helpful in understanding her view of the opportunities and challenges faced by
      public or community health nurses of the time.

PMID- 17553029
TI  - No association between MDM2 SNP309 promoter polymorphism and basal cell carcinoma
      of the skin.
AB  - BACKGROUND: The MDM2 oncoprotein promotes cell survival and cell cycle
      progression by inhibiting the p53 tumour suppressor protein. Further,
      overexpression of the MDM2 gene can inhibit DNA double-strand break repair in a
      p53-independent manner. Recent studies have shown that a single nucleotide
      polymorphism (SNP) in the intronic promoter region of MDM2 (called SNP309) can
      significantly change the expression of MDM2 and thereby suppress the p53 pathway.
      This SNP was also found to be associated with the onset and risk of different
      cancer types. Basal cell carcinoma of the skin (BCC) is one of the most common
      neoplasms in the world. BCC development is associated with environmental factors
      (especially sun exposure) as well as heritable factors. OBJECTIVES: The present
      case-control study investigated the association of the MDM2 SNP309 with the risk
      and the age at onset of BCC. Methods Data from 509 individuals affected by BCC
      and 513 healthy controls were genotyped with TaqMan polymerase chain reaction.
      RESULTS: Cases and controls showed a similar genotype distribution and the SNP
      did not modify the age at onset of BCC. CONCLUSIONS: These results suggest that
      the MDM2 SNP309 alone affects neither the risk nor the age at onset of BCC.

PMID- 17553030
TI  - Associations of promoter region polymorphisms in the tumour necrosis factor-alpha
      gene and early-onset psoriasis vulgaris in a northern Polish population.
AB  - BACKGROUND: Tumour necrosis factor (TNF)-alpha is considered to be an important
      mediator in the pathogenesis of psoriasis. Increased levels and activity of this
      cytokine have been observed in blood and skin of patients with psoriasis. As
      certain allelic variants of the TNF-alpha gene are associated with increased or
      decreased production of TNF-alpha, the disturbed cytokine balance may be under
      genetic control. OBJECTIVES: To investigate the potential association of TNF
      alpha promoter alleles within subtypes of psoriasis compared with healthy
      controls in a northern Polish population. METHODS: We analysed 166 patients with
      psoriasis vulgaris (134 with type I and 32 with type II) and 65 healthy controls.
      The polymorphisms -238G/A and -308G/A in the promoter region of the TNF-alpha
      gene were typed using the amplification refractory mutation system-polymerase
      chain reaction method. RESULTS: We found that the TNF-alpha-308A allele frequency
      was significantly decreased among patients with early-onset psoriasis in
      comparison with control subjects (7.5% vs. 15.4%, P = 0.022), whereas in the same
      patients the frequency of the TNF-alpha-238A allele was significantly increased
      as compared with the controls (16.8% vs. 3.1%, P = 0.000017, odds ratio 8.79, 95%
      confidence interval 2.606-29.678). Patients with early-onset psoriasis with -238
      genotype GA or AA were found more often among those with age at onset < 25 years
      in comparison with those with genotype GG (31.7% vs. 9.1%, P = 0.0312). We also
      found that the mean +/- SD age at onset among -238A carriers was significantly
      lower in comparison with that associated with the -238GG genotype (13.5 +/- 7.4
      vs. 19.2 +/- 9.9 years, P = 0.0132). CONCLUSIONS: Our study confirming the
      association between -238 G/A TNF-alpha promoter polymorphism and early-onset
      psoriasis vulgaris in the northern Polish population suggests that the -238A
      variant may contribute not only to a predisposition to psoriasis vulgaris but
      also to the disease phenotype.

PMID- 17553031
TI  - Long-term culture of multibacillary leprosy macrophages isolated from skin
      lesions: a new model to study Mycobacterium leprae-human cell interaction.
AB  - BACKGROUND: Leprosy is characterized by a disease spectrum having two polar
      clinical forms dependent on the presence or not of cell-mediated immunity. In the
      tuberculoid forms, granuloma-activated macrophages kill Mycobacterium leprae in
      conjunction with a Th1 response while, in multibacillary (MB) lesions, M. leprae
      nonactivated macrophages infiltrate the nerves and internal organs together with
      a Th2 response. The functional properties and activation pathways of macrophages
      isolated from patients with MB leprosy remain only partially understood.
      OBJECTIVES: To establish an ex vivo methodology capable of evaluating the
      activation pathways, grade and fate of cultured macrophages isolated from MB
      lesions. METHODS: Skin biopsies from patients with borderline tuberculoid,
      bordeline lepromatous and lepromatous leprosy (LL) were characterized by
      immunohistochemistry and transcriptional analysis. To isolate inflammatory cells,
      a portion of the samples was submitted to enzymatic digestion. These same cells,
      maintained in culture for a minimum 7-day period, were characterized
      morphologically and via flow cytometry at different culture time points. Cytokine
      [interferon (IFN)-gamma, tumour necrosis factor (TNF)-alpha and interleukin (IL)
      10] mRNA levels were quantified by real-time polymerase chain reaction and
      protein secretion in the culture supernatants was measured by enzyme-linked
      immunosorbent assay and the nitric oxide levels by Griess reagent. RESULTS: RNA
      expression in tuberculoid and MB lesions showed the profile expected of
      characteristic Th1 and Th2 responses, respectively. The inflammatory cells in all
      biopsies were successfully isolated. Although the number of cells varied between
      biopsies, it was highest in LL biopsies. The frequency of isolated CD14+ and CD3+
      cells measured by flow cytometry correlated with the percentages of macrophages
      and lymphocytes in the lesions. Throughout the culture period, CD68+ macrophages
      showed morphological changes. A progressive increase in cell number and reduction
      of infected cells were perceptible in the cultures. In contrast to the biopsies,
      TNF-alpha, IFN-gamma and IL-10 expression in the tuberculoid and MB leprosy cells
      in 24-h culture and the cytokine levels in the supernatants did not differ
      significantly. During the culture period, cytokine expression in the MB cells
      progressively declined, whereas, from days 1 to 7, nitrite levels progressively
      increased. After day 40, the remaining macrophages were able to ingest
      fluorescein isothiocyanate-labelled M. leprae. These data need to be confirmed.
      CONCLUSIONS: This study confirmed the feasibility of obtaining ex vivo
      macrophages from leprosy lesions and keeping them in long-term culture. This
      procedure may open new pathways to studying the interaction between M. leprae and
      human macrophages, which might, in turn, lead to the development of therapeutic
      tools capable of overcoming the specific anergy found in patients with MB
      leprosy.

PMID- 17553032
TI  - Hydroxycarbamide: a treatment for lichen sclerosus?

PMID- 17553033
TI  - A cytotoxic analysis of antiseptic medication on skin substitutes and autograft.
AB  - BACKGROUND: There is an increasing demand for the clinical application of human
      skin substitutes (HSSs) for treating ulcers, burns and surgical wounds. Due to
      this increasing demand and due to the simultaneous requirement for the
      administration of topical antiseptic medications, there is a need to determine
      potential cytotoxic effects of these medications on HSSs compared with autograft
      skin. OBJECTIVES: To perform such an evaluation. METHODS: Two different HSSs were
      used (autologous reconstructed epidermis on fibroblast-populated human dermis and
      allogeneic reconstructed epidermis on a fibroblast-populated rat collagen gel)
      and were compared with conventional full-thickness autograft. Twelve different
      antiseptics were applied topically to the stratum corneum in vitro for 24 h. The
      degree of cytotoxicity was analysed as detrimental changes in histology,
      metabolic activity (MTT assay) and RNA staining of tissue sections. RESULTS: The
      antiseptic medications tested showed different degrees of cytotoxicity. Acticoat,
      Aquacel Ag, Dermacyn, Fucidin, 0.5% silver nitrate solution and chlorhexidine
      digluconate were not cytotoxic for either HSS or autograft, and can therefore be
      used as required. Flamazine and zinc oxide cream resulted in moderate
      cytotoxicity. However, application of Betadine((R)), cerium-silver sulfadiazine
      cream, silver sulfadiazine cream with 1% acetic acid and Furacine resulted in a
      substantial decrease in cell viability and a detrimental effect on tissue
      histology when applied to autograft and especially to HSS. CONCLUSIONS: Due to
      the potential cytotoxic effect of some antiseptics on HSS, it is advised that
      clinicians balance the cytotoxicity of the medication, its antiseptic properties
      and the severity of colonization in choosing which one to apply.

PMID- 17553034
TI  - Livedo racemosa and digital necrosis in a patient with primary seronegative
      antiphospholipid syndrome and fibromuscular dysplasia of peripheral arteries.

PMID- 17553035
TI  - Hairdressing is associated with scalp disease in African schoolchildren.
AB  - BACKGROUND: Anecdotal reports suggest that certain disorders are common in
      African hair and may be associated with hairstyles. OBJECTIVES: A cross-sectional
      study of 1042 schoolchildren was performed to test this hypothesis. METHODS: A
      questionnaire was administered and scalp examinations performed, after ethics
      approval. RESULTS: Participants included 45% boys and 55% girls. The majority of
      boys, 72.8%, kept natural hair with frequent haircuts (within 4 weeks). The
      prevalence of acne (folliculitis) keloidalis nuchae (AKN) was 0.67% in the whole
      group and highest (4.7%) in boys in the final year of high school, all of whom
      had frequent haircuts. The majority of girls (78.4%) had chemically relaxed hair,
      which was usually combed back or tied in ponytails, vs. 8.6% of boys. Traction
      alopecia (TA) was significantly more common with relaxed than natural hair, with
      an overall prevalence of 9.4% (98 of 1042) and of 17.1% in girls, in whom it
      increased with age from 8.6% in the first year of school to 21.7% in the last
      year of high school. The proportion with TA in participants with a history of
      braids on natural hair was lower (22.9%), but not significantly, than among those
      with a history of braids on relaxed hair (32.1%). No cases of central centrifugal
      cicatricial alopecia were identified. CONCLUSIONS: We found associations between
      hairstyle and disease in our population of schoolchildren. AKN appears to be
      associated with frequently cut natural hair and TA with relaxed hair. These
      associations need further study for purposes of disease prevention.

PMID- 17553036
TI  - Prevalence of metabolic syndrome in patients with psoriasis: a hospital-based
      case-control study.
AB  - BACKGROUND: Psoriasis is a chronic inflammatory disease associated with an
      increased cardiovascular risk. Metabolic syndrome is a significant predictor of
      cardiovascular events. OBJECTIVE: To investigate the prevalence of metabolic
      syndrome in patients with psoriasis. METHODS: We performed a hospital-based case
      control study on 338 adult patients with chronic plaque psoriasis and 334
      patients with skin diseases other than psoriasis. RESULTS: Metabolic syndrome was
      significantly more common in psoriatic patients than in controls (30.1% vs.
      20.6%, odds ratio 1.65, 95% confidence interval 1.16-2.35; P = 0.005) after the
      age of 40 years. Psoriatic patients also had a higher prevalence of
      hypertriglyceridaemia and abdominal obesity, whereas hyperglycaemia, arterial
      hypertension and high-density lipoprotein cholesterol plasma levels were similar.
      Although psoriasis patients were more frequently smokers, the association of
      psoriasis with metabolic syndrome was independent from smoking. There was no
      correlation between severity of psoriasis and prevalence of metabolic syndrome.
      Psoriatic patients with metabolic syndrome were older and had a longer disease
      duration compared with psoriatic patients without metabolic syndrome. CONCLUSION:
      Psoriatic patients have a higher prevalence of metabolic syndrome, which can
      favour cardiovascular events. We suggest psoriatic patients should be encouraged
      to correct aggressively their modifiable cardiovascular risk factors.

PMID- 17553037
TI  - The challenge of follow-up in narrowband ultraviolet B phototherapy.
AB  - BACKGROUND: The use of narrowband ultraviolet (UV) B phototherapy to treat
      psoriasis and other disorders has increased markedly since the TL-01 lamps were
      introduced in the 1980s. While broadband UVB phototherapy has generally been
      considered to be a relatively safe treatment, some concern has been raised about
      the potential increased skin cancer risk with narrowband UVB. OBJECTIVES: The
      likelihood of a patient who is free of nonmelanoma skin cancer (NMSC) at the
      start of phototherapy developing a malignancy after a certain follow-up period
      will be dependent not only on the carcinogenic potential of the treatment but
      also on the age-conditional probability of natural occurrence. We were interested
      to explore the potential difficulty of designing studies to separate these two
      events. Methods Mathematical models were developed that combined age-conditional
      probabilities of developing NMSC due to natural causes with the risk of inducing
      these cancers from narrowband UVB phototherapy in order to estimate the excess
      number of cancers resulting from this therapeutic intervention in a cohort of
      patients. RESULTS: Within-department studies will be most unlikely to demonstrate
      that the number of NMSCs observed in follow-up studies is significantly different
      from that expected in an untreated population, even for a follow-up period of 20
      years. CONCLUSIONS: Determination of the carcinogenic potential associated with
      narrowband UVB will require large multicentre studies typically involving several
      thousand new patients per year and followed up for 10 years or more.

PMID- 17553038
TI  - Impaired cutaneous wound healing in granulocyte/macrophage colony-stimulating
      factor knockout mice.
AB  - BACKGROUND: Wound healing involves various cells and cytokines, resulting in the
      regular progression of remodelling events. Granulocyte/macrophage colony
      stimulating factor (GM-CSF) is a multifunctional pleiotropic cytokine and is
      known to facilitate wound healing, although the precise molecular and cellular
      mechanisms remain to be explored. OBJECTIVES: To use GM-CSF gene knockout (GM-CSF
      KO) mice to investigate the role of GM-CSF in cutaneous wound healing following
      full-thickness skin injury. METHODS: Full-thickness skin wounds were made in GM
      CSF KO and wild-type mice. The wound closure, leucocyte infiltration,
      vascularization and extent of cytokine production were determined. RESULTS: Wound
      healing was significantly delayed in GM-CSF KO mice, accompanied by reduced
      cytokine production (interleukin-6, monocyte chemoattractant protein-1 and
      macrophage inflammatory protein-2), and platelet-endothelial cell adhesion
      molecule-1 expression. Consequently there was reduced recruitment of neutrophils
      and macrophages and reduced vascularization in the wounds of GM-CSF KO mice.
      Although collagen deposition was delayed, it was significantly increased in the
      wounds of the GM-CSF KO mice in the later stages of wound healing. CONCLUSIONS:
      We conclude that GM-CSF plays an important role in the complex network of
      effector molecules that regulate keratinocyte proliferation and the inflammatory
      response. These data have important implications for further development of the
      therapeutic manipulation of wound healing using GM-CSF.

PMID- 17553039
TI  - The optimal use of bexarotene in cutaneous T-cell lymphoma.
AB  - The management goal in cutaneous T-cell lymphomas (CTCLs) is to improve symptoms
      and induce remission. Early-stage disease is generally treated with skin-directed
      therapies. However, if these do not control the disease, systemic therapy becomes
      necessary. Bexarotene, a novel rexinoid, is an oral, noncytotoxic drug that has
      been approved in Europe for the treatment of refractory advanced-stage CTCL and
      in the U.S.A. for refractory CTCL. We provide guidance on the use of bexarotene
      in the management of CTCL, based on data from phase II/III clinical trials and
      the authors' clinical experience, and suggest how the potential of the drug can
      be maximized. The clinical trial results with bexarotene are reviewed, especially
      in comparison with interferon-alpha, which is the other commonly used
      noncytotoxic systemic therapy for CTCL. A treatment algorithm for bexarotene in
      refractory CTCL is suggested. As bexarotene may take time to achieve a maximum
      response, this algorithm recommends that therapy should be continued for a
      sufficient period to allow for a delayed onset of action. In addition, possible
      combination therapies with bexarotene are discussed. We conclude that bexarotene
      is effective in the management of CTCL, and has the advantage of oral
      administration. An on-going randomized clinical trial comparing psoralen plus
      ultraviolet A (PUVA) with PUVA plus bexarotene will provide valuable information
      about this combination regimen in early-stage disease, but further data are
      needed on the relative efficacies of other combination therapies with bexarotene
      in CTCL.

PMID- 17553040
TI  - Bartonella-related pseudomembranous angiomatous papillomatosis of the oral cavity
      associated with allogeneic bone marrow transplantation and oral graft-versus-host
      disease.
AB  - Patients undergoing allogeneic stem cell transplantation are at high risk for
      infection with a variety of pathogens during different phases of the procedure.
      Human infections due to Bartonella spp. are viewed as emerging diseases typical
      in, although not exclusive to, immunosuppressed patients, in particular those
      with AIDS, organ transplants and haematological malignancies. We describe four
      patients, three children and one adult, who developed vegetating papillomatous
      lesions exclusively on the oral mucosae. They shared a history of haematological
      malignancy and allogeneic bone marrow/stem cell transplantation, and later
      developed chronic graft-versus-host disease, also involving the oral mucosae.
      Histopathologically, the vegetating lesions were characterized by a diffuse
      neoangiogenesis, granulation-like tissue, and a mixed cell infiltrate
      predominantly composed of neutrophils. Gram-negative bacteria were found in the
      endothelial cells of the vessels in the deeper portion of the corium by electron
      microscopy. In three cases, DNA of B. henselae was detected by polymerase chain
      reaction (PCR), and confirmed by sequencing of the PCR products. All the lesions
      healed after systemic antibiotic therapy, although some recurred after months,
      and regressed again after systemic antibiotic treatment associated with
      conservative surgical excision.

PMID- 17553041
TI  - Systemic sclerosis in association with peristomal pyoderma gangrenosum.

PMID- 17553042
TI  - Dermoscopic pattern of intermediate stage in seborrhoeic keratosis regressing to
      lichenoid keratosis: report of 24 cases.
AB  - BACKGROUND: Lichenoid keratosis (LK) is a well-described entity which has been
      proposed to represent an immunological or regressive response to pre-existing
      epidermal lesions such as solar lentigines or seborrhoeic keratoses. OBJECTIVES:
      To evaluate the dermoscopic criteria of a series of cases of LK with remaining
      areas of seborrhoeic keratosis which were both dermoscopically and histologically
      diagnosed. METHODS: Pigmented lesions with dermoscopic areas of seborrhoeic
      keratosis and LK in the same tumour were consecutively diagnosed and
      prospectively included in the study. All pigmented lesions were examined and
      registered using DermLite Foto equipment (3Gen, LLC, Dana Point, CA, U.S.A.), at
      10-fold magnification, at the Dermatology Department of Hospital de Sant Pau i
      Santa Tecla (Tarragona, Spain), between 1 January 2003 and 31 December 2005.
      RESULTS: In total, 24 cases of lesions with dermoscopic areas of seborrhoeic
      keratosis and LK were collected. In four lesions (17%), the clinical differential
      diagnosis without dermoscopy included malignant melanoma and in seven lesions
      (29%), basal cell carcinoma. The diagnosis of LK was clinically considered
      without dermoscopy in only six cases (25%). A granular pattern was observed to be
      distributed throughout the LK areas of the lesions. This pattern consisted of the
      presence of brownish-grey, bluish-grey or whitish-grey coarse granules that
      formed, in 11 cases (46%), globules and/or short lines. In one lesion, located on
      the face, these short lines produced annular or rhomboid structures as seen in
      lentigo maligna melanoma. CONCLUSIONS: Dermoscopy is a useful tool which assists
      in the correct clinical recognition of LK, which may also potentially illuminate
      the pathogenesis of these tumours, showing the intermediate stage of regressing
      epidermal lesions in an LK.

PMID- 17553043
TI  - Recessive dystrophic epidermolysis bullosa associated with dilated
      cardiomyopathy.

PMID- 17553044
TI  - Consecutive use of different biological therapies in the treatment of psoriasis.

PMID- 17553045
TI  - Cutaneous mercury deposits after henna dye application in the arm.

PMID- 17553046
TI  - Hypocomplementaemic urticarial vasculitis associated with non-Hodgkin lymphoma
      and treatment with intravenous immunoglobulin.

PMID- 17553047
TI  - Severe persistent pemphigoid gestationis: long-term remission with rituximab.

PMID- 17553048
TI  - Metastatic calcinosis cutis presenting as bilateral vulval cysts.

PMID- 17553049
TI  - Actinic prurigo deterioration due to degradation of DermaGard window film.

PMID- 17553050
TI  - Successful treatment of primary cutaneous follicle centre lymphoma with topical
      5% imiquimod.

PMID- 17553051
TI  - A multicentre, randomized, controlled study of the efficacy, safety and cost
      effectiveness of a combination therapy with amorolfine nail lacquer and oral
      terbinafine compared with oral terbinafine alone for the treatment of
      onychomycosis with matrix involvement.
AB  - BACKGROUND: Onychomycosis is common, accounting for up to 50% of all nail
      disorders. Toenail onychomycosis can cause nail deformity, embarrassment, pain
      and walking difficulties. Some populations, such as individuals with diabetes,
      are at higher risk for developing secondary complications such as infections.
      Treatment takes many months and therapeutic choices can increase clinical
      effectiveness, lower toxicity and minimize healthcare costs. OBJECTIVES: Based on
      the results of a previous pilot study, the objective of the present study was to
      show, in a larger population, the enhanced efficacy of a combination of
      amorolfine nail lacquer and oral terbinafine in the treatment of onychomycosis
      with matrix involvement. In addition, a cost-effectiveness analysis was
      performed. METHODS: In this multicentre, randomized, open-label, parallel group
      study, patients were randomized to receive either a combination of amorolfine
      hydrochloride 5% nail lacquer once weekly for 12 months plus terbinafine 250 mg
      once daily for 3 months (AT group) or terbinafine alone once daily for 3 months
      (T group). The study duration was 18 months including a 6-month treatment-free
      phase following the 12-month active treatment phase for the AT group and a 15
      month treatment-free phase following the 3-month active treatment phase for the T
      group. The primary efficacy criterion was overall response, dichotomized into
      success or failure, success being the combination of clinical cure and negative
      mycology at month 18. This criterion was used as the effectiveness measure in the
      pharmacoeconomic analysis, conducted from a payer perspective. RESULTS: In total,
      249 patients were included into the study: 120 in the AT group and 129 in the T
      group. A significantly higher success rate was observed for patients in the AT
      group relative to those in the T group at 18 months (59.2% vs. 45.0%; P = 0.03).
      Both treatment regimens were safe and well tolerated. Treatment cost per cured
      patient was lower for the combination than for terbinafine alone in all
      countries. CONCLUSIONS: Study results confirmed that, in the treatment of
      dermatophytic toenail onychomycosis with matrix involvement, amorolfine nail
      lacquer in combination with oral terbinafine enhances clinical efficacy and is
      more cost-effective than terbinafine alone.

PMID- 17553052
TI  - Selective biodegradation in hair shafts derived from archaeological, forensic and
      experimental contexts.
AB  - BACKGROUND: Hair is degraded by the action of both dermatophytic and
      nondermatophytic microorganisms. The importance of understanding hair sample
      condition in archaeological and forensic investigation highlights the need for a
      detailed knowledge of the sequence of degradation in samples that have been
      either buried or left exposed at the ground surface. OBJECTIVES: To investigate
      the sequence of biodegradative change to human terminal scalp hair from
      archaeological and forensic contexts. METHODS: Cut modern scalp hair from three
      individuals with caucasoid-type hair was inoculated with soil microorganisms
      through soil burial in the field and under laboratory conditions to produce
      experimentally degraded samples. The degraded hair fibres were subjected to
      detailed histological examination using a combination of high-resolution light
      microscopy, transmission electron microscopy and scanning electron microscopy to
      investigate the nature and sequence of degradative change to hair structural
      components. RESULTS/DISCUSSION: Degradation was found to occur first within the
      least structurally robust components that afford the least resistance to
      microbial/chemical attack. The sequence of degradation (most to least-reflecting
      degree of vulnerability) in the hair cuticle was as follows: (1) intercellular
      delta-layer (cell membrane complex); (2) endocuticle; (3) cell membrane beta
      layers; (4) exocuticle; (5) epicuticle; and (6) A-layer. In the hair cortex this
      was as follows: (I) intercellular delta-layer (cell membrane complex); (II) cell
      membrane beta-layers; (III) intermacrofibrillar matrix/nuclear remnants; (IV)
      microfibrils; (V) intermicrofibrillar matrix; and (VI) pigment granules (the hair
      fibre component that was the least vulnerable to degradation). CONCLUSIONS: The
      selective progress of degradation in the hair shaft has been charted and this
      provides a basis for further histological work in better understanding the
      condition of hair fibres derived from archaeological or forensic contexts as well
      as being relevant to investigation of diseased hair, in particular hair infected
      by dermatophytes and hair weakened by genetic hair shaft abnormalities.

PMID- 17553053
TI  - Proposal of a new classification system for melanocytic naevi.
AB  - The lack of consensus among clinicians and pathologists due to the mixture of
      clinical and histopathological features used to define the various melanocytic
      naevi underscores the need of a better classification system for these benign
      lesions. We describe a dermoscopic classification system for melanocytic naevi
      that is directed to clinicians dealing with the early diagnosis of melanoma, as
      well to pathologists, in order to promote better communication between these
      different specialists.

PMID- 17553054
TI  - First case series on the use of calcipotriol-betamethasone dipropionate for
      morphoea.

PMID- 17553055
TI  - Lipomas after blunt soft tissue trauma: are they real? Analysis of 31 cases.
AB  - BACKGROUND: Soft tissue trauma and lipomas are common occurrences in surgical
      practice. Lipomas are defined as benign tumours of adipose tissue with so far
      unexplained pathogenesis and aetiology. A link between preceding blunt soft
      tissue trauma at the site of the tumour and the formation of lipomas has been
      described earlier. These soft tissue tumours have been named 'post-traumatic
      lipomas'. OBJECTIVES: In a retrospective review, to analyse all patients with
      benign adipose tissue tumours treated at our institution between August 2001 and
      January 2007. METHODS: All cases were reviewed regarding medical history,
      magnetic resonance imaging findings, intraoperative findings, clinical chemistry
      and histology. RESULTS: In 170 patients presenting with lipomas, 34 lipomas in 31
      patients were identified as post-traumatic. The mean +/- SD age of the patients
      with post-traumatic lipomas was 52 +/- 14.5 years. The mean time elapsed between
      soft tissue trauma and lipoma formation was 2.0 years (range 0.5-5). Twenty-five
      of the 31 patients reported an extensive and slowly resolving haematoma after
      blunt tissue trauma at the site of lipoma formation. The mean +/- SD body mass
      index was 29.0 +/- 7.6 kg m(-2). Fourteen of 31 patients presented with an
      elevated partial thromboplastin time. Eleven of 34 lipomas were found on the
      upper extremities, five on the lower extremities, 13 on the trunk, and two on the
      face. All tumours were located subcutaneously, superficial to the musculofascial
      system. Thirty-three lipomas were removed by surgical excision and one by
      liposuction following an incisional biopsy. Histological examination revealed
      capsulated and noncapsulated benign adipose tissue in all 34 tumours.
      CONCLUSIONS: The existence of a pathogenic link between blunt soft tissue trauma
      and the formation of post-traumatic lipomas is still controversial. Two potential
      mechanisms are discussed. Firstly, the formation of so-called post-traumatic
      'pseudolipomas' may result from a prolapse of adipose tissue through fascia
      induced by direct impact. Alternatively, lipoma formation may be explained as a
      result of preadipocyte differentiation and proliferation mediated by cytokine
      release following soft tissue damage after blunt trauma and haematoma formation.

PMID- 17553057
TI  - A case of milium-like syringoma with focal calcification in Down syndrome.

PMID- 17553056
TI  - Impetigo in epidemic and nonepidemic phases: an incidence study over 4(1/2) years
      in a general population.
AB  - BACKGROUND: Little is known about incidence and natural variation of impetigo in
      general populations. OBJECTIVES: To investigate the natural course of impetigo in
      a well-defined population, and to study the resistance pattern of the causal
      bacteria over time. METHODS: This is a population-based incidence study in
      Austevoll, an island community of 4457 inhabitants in Norway, in the years 2001
      2005. Incidence rates are given as events per person-year. Epidemic periods were
      identified by statistical process-control analyses. RESULTS: The incidence rate
      of impetigo for the whole study period was 0.017 events per person-year,
      corresponding to a total of 334 cases. The incidence rates were 0.009, 0.026,
      0.019, 0.016 and 0.009 in the years 2001, 2002, 2003, 2004 and 2005,
      respectively. Three epidemics were identified, starting in August of 2002, 2003
      and 2004, lasting for 11, 11 and 5 weeks, respectively. Incidence rates in these
      epidemic periods were 0.099, 0.045 and 0.074, respectively. In epidemic periods,
      Staphylococcus aureus was the causal bacterium in 89% (117/132) of cases, while
      this proportion was 68% (84/123) in nonepidemic periods (P < 0.01).
      Staphylococcus aureus was resistant to fusidic acid in 84% (98/117) and 64%
      (54/84) of impetigo cases in epidemic and nonepidemic periods, respectively (P <
      0.01). When investigating all types of infections caused by S. aureus in the
      study period, the proportion of fusidic acid resistance in impetigo cases
      (152/201, 76%) differed significantly from fusidic acid resistance in other
      infections (18/116, 16%) (P < 0.01). CONCLUSIONS: Distinctive epidemic outbreaks
      occurred during the summer of three of the five follow-up years. In outbreaks, S.
      aureus was more frequently the causal agent and the sensitivity to fusidic acid
      decreased significantly.

PMID- 17553058
TI  - Artificial reduction in transepidermal water loss improves skin barrier function.
AB  - BACKGROUND: Artificial reduction of abnormal transepidermal water loss (TEWL) is
      considered to improve skin diseases associated with a defective barrier function.
      Treatment of the skin with moisturizers is also known to influence skin barrier
      function. Whether or not differences in occlusion between creams contribute to
      their effects on the skin barrier function is unknown. OBJECTIVES: To investigate
      the long-term effects of a semipermeable membrane on the skin barrier function in
      normal skin. In addition, the occlusive properties of two creams were studied.
      METHODS: The study was randomized, controlled and evaluator-blind using
      measurement of TEWL and skin susceptibility to sodium lauryl sulphate as
      indicators of skin barrier function. RESULTS: Coating of the skin with a silicone
      membrane for 23 h per day for 3 weeks improved skin barrier function, whereas no
      significant changes were found after using the membrane for 8 h per day.
      CONCLUSIONS: Differences between creams in terms of their effect on skin barrier
      function cannot be solely explained by their occlusive properties.

PMID- 17553059
TI  - The oncogenic potential of human papillomaviruses: a review on the role of host
      genetics and environmental cofactors.
AB  - Human papillomaviruses (HPVs), with over 100 genotypes, are a very complex group
      of human pathogenic viruses. In most cases, HPV infection results in benign
      epithelial proliferations (verrucae). However, oncogenic types of HPV may induce
      malignant transformation in the presence of cofactors. For example, over 99% of
      all cervical cancers and a majority of vulval, vaginal, anal and penile cancers
      are the result of oncogenic HPV types. Such HPV types have been increasingly
      linked to other epithelial cancers involving the skin, larynx and oesophagus.
      Although viral infection is necessary for neoplastic transformation, evidence
      suggests that host and environmental cofactors are also required. Research
      investigating HPV oncogenesis is complex and quite extensive. The inability to
      produce mature HPV virions in animal models has been a major limitation in fully
      elucidating the oncogenic potential and role of associated cofactors in promoting
      malignant transformation in HPV-infected cells. We have reviewed the literature
      and provide a brief account of the current understanding of HPV oncogenesis,
      emphasizing the role of genetic susceptibility, immune response, and
      environmental and infectious cofactors.

PMID- 17553060
TI  - Multisystem Erdheim-Chester disease; a unique presentation with liver and axial
      skeletal involvement.

PMID- 17553061
TI  - Combined treatment with intratumoral injection of dendritic cells and topical
      application of imiquimod for murine melanoma.
AB  - BACKGROUND: The maturation state of dendritic cells is one of the factors that
      affect their capacity to induce antigen-specific cytotoxic T lymphocytes. Topical
      cutaneous application of imiquimod can induce the maturation and migration of
      cutaneous dendritic cells. OBJECTIVES: To evaluate the synergistic effect of
      topical application of imiquimod plus intratumoral injection of syngeneic bone
      marrow-derived dendritic cells in the treatment of melanoma. METHODS: For the
      B16F10 melanoma model, naive C57BL/6 mice were inoculated intradermally with
      2x10(3) B16F10 melanoma cells in the right upper flank. Four groups (untreated
      control, dendritic cells alone, imiquimod alone and imiquimod plus dendritic
      cells) were included in the animal study, with five mice in each group. Tumour
      size was measured every 2 weeks, and histochemical and immunohistochemical
      staining carried out. ELISpot and PKH assays were performed to assess immune
      activity. RESULTS: Combined treatment of topical application of imiquimod and
      intratumoral injection of dendritic cells led to significant tumour regression,
      in contrast to partial eradication of the tumours with imiquimod or dendritic
      cells alone. CONCLUSION: These findings suggest that combination therapy with
      topical application of imiquimod and intratumoral administration of dendritic
      cells is a potent strategy for the treatment of melanoma.

PMID- 17553062
TI  - Dictyostelium differentiation-inducing factor-1 induces glucose transporter 1
      translocation and promotes glucose uptake in mammalian cells.
AB  - The differentiation-inducing factor-1 (DIF-1) is a signal molecule that induces
      stalk cell formation in the cellular slime mold Dictyostelium discoideum, while
      DIF-1 and its analogs have been shown to possess antiproliferative activity in
      vitro in mammalian tumor cells. In the present study, we investigated the effects
      of DIF-1 and its analogs on normal (nontransformed) mammalian cells. Without
      affecting the cell morphology and cell number, DIF-1 at micromolar levels dose
      dependently promoted the glucose uptake in confluent 3T3-L1 fibroblasts, which
      was not inhibited with wortmannin or LY294002 (inhibitors for
      phosphatidylinositol 3-kinase). DIF-1 affected neither the expression level of
      glucose transporter 1 nor the activities of four key enzymes involved in glucose
      metabolism, such as hexokinase, fluctose 6-phosphate kinase, pyruvate kinase, and
      glucose 6-phosphate dehydrogenase. Most importantly, stimulation with DIF-1 was
      found to induce the translocation of glucose transporter 1 from intracellular
      vesicles to the plasma membranes in the cells. In differentiated 3T3-L1
      adipocytes, DIF-1 induced the translocation of glucose trasporter 1 (but not of
      glucose transporter 4) and promoted glucose uptake, which was not inhibited with
      wortmannin. These results indicate that DIF-1 induces glucose transporter 1
      translocation and thereby promotes glucose uptake, at least in part, via a
      inhibitors for phosphatidylinositol 3-kinase/Akt-independent pathway in mammalian
      cells. Furthermore, analogs of DIF-1 that possess stronger antitumor activity
      than DIF-1 were less effective in promoting glucose consumption, suggesting that
      the mechanism of the action of DIF-1 for stimulating glucose uptake should be
      different from that for suppressing tumor cell growth.

PMID- 17553063
TI  - Modulation of aryl hydrocarbon receptor transactivation by carbaryl, a
      nonconventional ligand.
AB  - Carbaryl (1-naphthyl-N-methylcarbamate), a widely used carbamate insecticide,
      induces cytochrome P450 1A gene expression in mammalian cells. This activity is
      usually mediated by the interaction of the compound with the aryl hydrocarbon
      receptor. However, it has been proposed that this mechanism does not apply to
      carbaryl because its structure differs from that of typical aryl hydrocarbon
      receptor ligands. We show here that carbaryl promotes activation of target genes
      in a yeast-based bioassay expressing both aryl hydrocarbon receptor and aryl
      hydrocarbon receptor nuclear translocator. By contrast, carbaryl acted as a
      competitive inhibitor, rather than as an agonist, in a simplified yeast system,
      in which aryl hydrocarbon receptor nuclear translocator function is bypassed by
      fusing aryl hydrocarbon receptor to a heterologous DNA binding domain. This dual
      action of carbaryl, agonist and partial antagonist, was also observed by
      comparing carbaryl response in two vertebrate cell lines. A yeast two-hybrid
      assay showed that the mammalian coactivator cAMP response element-binding protein
      readily interacts with aryl hydrocarbon receptor bound to its canonical ligand
      beta-naphthoflavone, but not with the carbaryl-aryl hydrocarbon receptor complex.
      We propose that carbaryl interacts with aryl hydrocarbon receptor, but that its
      peculiar structure imposes a substandard configuration on the aryl hydrocarbon
      receptor ligand-binding domain that prevents interaction with key coactivators
      and activates transcription without the need for aryl hydrocarbon receptor
      nuclear translocator. This effect may be relevant in explaining its physiological
      effects in exposed animals, and may help to predict its effects, and that of
      similar compounds, in humans. Our data also identify the aryl hydrocarbon
      receptor/cAMP response element-binding protein interaction as a molecular target
      for the identification and development of new aryl hydrocarbon receptor
      antagonists.

PMID- 17553064
TI  - Protein kinase C epsilon phosphorylates keratin 8 at Ser8 and Ser23 in GH4C1
      cells stimulated by thyrotropin-releasing hormone.
AB  - Protein kinase C epsilon (PKCepsilon) is activated by thyrotropin-releasing
      hormone (TRH), a regulator of pituitary function in rat pituitary GH(4)C(1)
      cells. We analyzed the downstream mechanism after PKCepsilon activation. Exposure
      of GH(4)C(1) cells to TRH or a phorbol ester increased the phosphorylation of
      three p52 proteins (p52a, p52b and p52c) and decreased the phosphorylation of
      destrin and cofilin. GF109203X, an inhibitor of protein kinases including PKC,
      inhibited phosphorylation of the p52 proteins by TRH stimulation. Peptide
      mapping, amino-acid sequencing, and immunochemical studies indicated that p52a,
      p52b, and p52c are the differentially phosphorylated isoforms of keratin 8 (K8),
      an intermediate filament protein. The unphosphorylated K8 (p52n) localized
      exclusively to the cytoskeleton, whereas the phosphorylated forms (especially
      p52c), which are increased in TRH-stimulated cells, localized mainly to the
      cytosol. K8 phosphorylation was enhanced in PKCepsilon-overexpressing clones, and
      purified recombinant PKCepsilon directly phosphorylated K8 with a profile similar
      to that observed in TRH-stimulated cells. PKCepsilon and K8 colocalized near the
      nucleus under basal conditions and were concentrated in the cell periphery and
      cell-cell contact area after TRH stimulation. MS analyses of phospho-K8 and K8
      synthesized peptide (amino acids 1-53) showed that PKCepsilon phosphorylates Ser8
      and Ser23 of K8. Phosphorylation of these sites is enhanced in TRH-stimulated
      cells and PKCepsilon-overexpressing cells, as assessed by immunoblotting using
      antibodies to phospho-K8. These results suggest that K8 is a physiological
      substrate for PKCepsilon, and the phosphorylation at Ser8 and Ser23 transduces,
      at least in part, TRH-PKCepsilon signaling in pituitary cells.

PMID- 17553065
TI  - Genomics of IncP-1 antibiotic resistance plasmids isolated from wastewater
      treatment plants provides evidence for a widely accessible drug resistance gene
      pool.
AB  - The dramatic spread of antibiotic resistance is a crisis in the treatment of
      infectious diseases that affect humans. Several studies suggest that wastewater
      treatment plants (WWTP) are reservoirs for diverse mobile antibiotic resistance
      elements. This review summarizes findings derived from genomic analysis of IncP-1
      resistance plasmids isolated from WWTP bacteria. Plasmids that belong to the IncP
      1 group are self-transmissible, and transfer to and replicate in a wide range of
      hosts. Their backbone functions are described with respect to their impact on
      vegetative replication, stable maintenance and inheritance, mobility and plasmid
      control. Accessory genetic modules, mainly representing mobile genetic elements,
      are integrated in-between functional plasmid backbone modules. These elements
      carry determinants conferring resistance to nearly all clinically relevant
      antimicrobial drug classes, to heavy metals, and quaternary ammonium compounds
      used as disinfectants. All plasmids analysed here contain integrons that
      potentially facilitate integration, exchange and dissemination of resistance gene
      cassettes. Comparative genomics of accessory modules located on plasmids from
      WWTP and corresponding modules previously identified in other bacterial genomes
      revealed that animal, human and plant pathogens and other bacteria isolated from
      different habitats share a common pool of resistance determinants.

PMID- 17553066
TI  - Minute pleomorphic adenoma of the submandibular gland in patients with oral
      malignancy: a report of two cases with histological and immunohistochemical
      examination.

PMID- 17553067
TI  - A subgroup of intrahepatic cholangiocarcinoma with an infiltrating replacement
      growth pattern and a resemblance to reactive proliferating bile ductules: 'bile
      ductular carcinoma'.
AB  - AIMS: The histogenesis and biological behaviour of peripheral intrahepatic
      cholangiocarcinoma (peripheral CC) remain unclarified. The aim of this study was
      to examine the growth pattern of peripheral CC (24 cases) in comparison with
      hepatocellular carcinoma (HCC, 27 cases) and metastatic colorectal adenocarcinoma
      (MCA, 24 cases). METHODS AND RESULTS: Tumour/surrounding liver borders were
      classified as: (i) fibrous encapsulation, (ii) compressive growth, and (iii)
      infiltrating replacement. Nineteen of 24 peripheral CCs showed (iii), whereas 23
      of 27 HCCs showed (i) and 17 of 24 MCAs showed (ii). In (iii), carcinoma cells
      infiltrated the surrounding liver without compression, and hepatic supporting
      vascular structures such as portal tracts were secondarily incorporated into the
      tumour. In (i) and (ii), the surrounding liver was compressed and no or few
      portal tracts were incorporated within the tumour. Fifteen of 24 peripheral CCs
      were composed of carcinoma cells resembling reactive bile ductules and these
      cells were positive for neural cell adhesion molecule (NCAM), a marker of
      proliferating bile ductules. The remaining nine peripheral CCs were composed of
      ordinary adenocarcinoma and negative for NCAM. CONCLUSIONS: A subgroup of
      peripheral CCs with an infiltrating replacement growth pattern resembles reactive
      bile ductules and expresses NCAM. 'Bile ductular carcinoma' may be a better term
      for this subgroup.

PMID- 17553068
TI  - Atrial pacing inducing narrow QRS tachycardia followed by wide complex
      tachycardia.

PMID- 17553069
TI  - A novel finding--isolated Marshall's ligament rhythm after catheter ablation and
      reconnection of the Marshall's ligament with the left atrium after an adenosine
      bolus in one patient with atrial fibrillation.

PMID- 17553070
TI  - Non-antiarrhythmic drugs in atrial fibrillation: a review of non-antiarrhythmic
      agents in prevention of atrial fibrillation.
AB  - This article reviews current evidence of non-antiarrhythmic agents for the
      prevention and maintenance of sinus rhythm in patients with atrial fibrillation.
      These nontraditional agents include angiotensin converting enzyme inhibitors,
      angiotensin receptor blockers, antiinflammatory agents, calcium channel blockers,
      and beta-blockers. The mechanisms of action and clinical trials regarding the
      effectiveness of these agents in atrial fibrillation prevention are reviewed.

PMID- 17553071
TI  - Rhythmic ECG changes in a patient with long QT syndrome type 3.

PMID- 17553072
TI  - Postprandial augmentation of bradycardia-dependent ST elevation in patients with
      Brugada syndrome.
AB  - INTRODUCTION: In patients with Brugada syndrome, the circadian variation of ST
      elevation could be modulated by the autonomic nervous activity and RR interval.
      Recently, glucose-induced insulin secretion was also reported to contribute to
      fluctuation of ST elevation. Therefore, we assessed the effects of taking meals
      on the ST-RR relationship in the daily life of patients with Brugada syndrome.
      METHODS AND RESULTS: Twenty-eight patients with Brugada syndrome, who had the
      type I ST elevation, were categorized into 12 symptomatic and 16 asymptomatic
      patients. Unipolar lead (V2) Holter ECG was recorded and ST-RR relationships for
      a 2-hour period were compared before and after each meal. From ST-RR linear
      regression lines, ST-RR slope (mm/sec) and ST(mm) at RR intervals of both 0.6
      seconds and 1.2 seconds (ST(0.6) and ST(1.2)) were determined. The ST-RR slope
      increased significantly after lunch (2.6 +/- 0.4 vs 4.4 +/- 1.2, P < 0.05) and
      dinner (2.1 +/- 1.0 vs 5.2 +/- 1.9, P < 0.01) in symptomatic patients, but not in
      asymptomatic patients. In both groups, ST(0.6) was not different before or after
      each meal. However, ST(1.2) increased after each meal in symptomatic patients.
      After dinner, ST(1.2) was significantly higher in symptomatic patients than in
      asymptomatic patients (5.0 +/- 2.7 vs 3.6 +/- 0.8, P < 0.05). Postprandial
      increase in both ST-RR slope and ST(1.2) was greatest at dinner in symptomatic
      patients; however, this tendency was not seen in asymptomatic patients.
      CONCLUSIONS: In symptomatic patients with Brugada syndrome, bradycardia-dependent
      augmentation of ST elevation was enhanced for the postprandial period, especially
      after dinner. This could be related to occurrence of ventricular fibrillation in
      the late evening.

PMID- 17553073
TI  - Time to electrode rewarming after cryoablation predicts lesion size.
AB  - INTRODUCTION: There are no methods in clinical use to assess tissue cooling
      during catheter cryoablation. Cryoablation electrode temperature may be a poor
      predictor of lesion size. The purpose of this study was to determine whether the
      time necessary for the cryoablation electrode to cool to target temperature or to
      rewarm after cryoablation can predict lesion size. METHODS AND RESULTS:
      Cryoablation was performed on live porcine left ventricle in a saline bath (37
      degrees C) using 8-mm-tip catheter. Cryoablation was given for 300 seconds under
      all permutations of the following conditions: electrode orientation vertical or
      horizontal, contact pressure 6 or 20 g, superfusate flow over electrode-tissue
      interface at 0.2 or 0.4 m/s (N = 10 each condition set, total 80 experiments).
      The time intervals necessary to cool the electrode to the target temperature of 
      75 degrees C and to rewarm to + 30 degrees C after termination of cryoablation
      were recorded. Lesion volume was predicted best by the time necessary to rewarm
      the electrode to +30 degrees C (r2 = 0.65, P < 0.0001), followed by electrode
      temperature (r2 = 0.28, P < 0.0001) and time to cool the electrode to -75 degrees
      C (r2 = 0.24, P < 0.0001). Time to +30 degrees C and time to -75 degrees C were
      associated with superfusate flow rate, contact pressure, and electrode
      orientation (r2 = 0.80 and 0.61, respectively, both P < 0.0001). Superfusate flow
      rate, contact pressure, and orientation were also highly predictive of lesion
      volume (r2 = 0.93, P < 0.0001). CONCLUSIONS: Time to cryoablation electrode
      rewarming is a better predictor of cryoablation lesion size than is electrode
      temperature. Time to cryoablation electrode rewarming reflects important
      determinants of cryoablation lesion formation--convective warming, contact
      pressure, and electrode orientation--that are not ascertainable during clinical
      ablation procedures.

PMID- 17553074
TI  - Atrial tachycardia transition during ablation of persistent atrial fibrillation:
      what is the mechanism?

PMID- 17553075
TI  - Comparison of high power, medium power, and irrigated-tip ablation strategies for
      pulmonary vein isolation in a canine model.
AB  - BACKGROUND: We sought to compare the efficacy and collateral damage during
      pulmonary vein (PV) isolation in a canine model using three different ablation
      strategies. METHODS: Normal dogs (three each) were randomized to high power (70
      W, 20 seconds, 60 degrees C, Hi), medium power (50 W, 60 seconds, 50 degrees C;
      Med), or irrigated-tip (35 W, 60 seconds, 45 degrees C; Cool) ablation. Two
      transseptal punctures were performed and right and left superior PV electrical
      isolation was performed using the assigned ablation strategy. Animals survived
      for 30 days. RESULTS: There was no difference in the number of lesions required
      to achieve PV isolation (Hi vs Med vs Cool; 43 vs 38 vs 44 lesions; P = NS). At
      sacrifice, Hi and Med lesions showed gross evidence of endocardial cratering and
      eschar formation. Corresponding histopathology showed transmural atrial necrosis
      with granulation tissue and fibrosis. Cool lesions demonstrated superficial
      endocardial white patches. The corresponding histopathology was subendocardial
      fibrosis with full and partial thickness necrosis of the atrial wall. One Hi
      animal had a large thrombus adherent to the left atrial wall above the left
      superior PV. PV stenosis was noted in one of three Hi and one of three Med, and
      none of three Cool. There were visible burns to the lung overlying the left
      atrial wall in one of three Hi, one of three Med, and none of three Cool. The
      esophagus demonstrated no evidence of serosal injury. CONCLUSIONS: The Hi and Med
      power 8-mm-tip ablation strategies for achieving PV isolation appear to result in
      excessive tissue destruction. Irrigated-tip lesions resulted in less endocardial
      eschar formation, PV stenosis, and damage to collateral structures.

PMID- 17553076
TI  - Intracardiac impedance monitors hemodynamic deterioration in a chronic heart
      failure pig model.
AB  - INTRODUCTION: A large number of heart failure (HF) patients benefit from cardiac
      resynchronization therapy. Measurements of intrathoracic impedance (ITZ) by
      implantable devices correlate with intrathoracic fluid content and are used for
      monitoring lung edema formation in HF patients. However, intrathoracic fluid is
      only an indirect parameter of cardiac function. We hypothesized that changes in
      intracardiac impedance correlate with left ventricular (LV) volume changes.
      Therefore, measurements of intracardiac impedance between a right ventricular
      lead and a LV lead may be used to monitor long-term changes of LV function.
      METHODS AND RESULTS: HF was successfully induced in nine mini-pigs by continuous
      high-rate pacing. Hemodynamic parameters as well as intracardiac impedance and
      ITZ were measured before HF induction and after 20 +/- 5 days of high-rate
      pacing. After the pacing period, we found a significant deterioration of
      hemodynamics, reflected by a reduction of ejection fraction from 71+/-11% to 48+/
      7% and an increase of LV end diastolic pressure (EDP) from 12 +/- 4 mmHg to 26 +/
      8 mmHg. Worsening of cardiac function correlated with a significant >30%
      decrease of end diastolic intracardiac impedance, in accordance with a >20%
      increase of end diastolic volume (EDV). ITZ decreased by more than 8%. We
      observed a significant inverse correlation between end diastolic intracardiac
      impedance and EDP (r =-0.81, P < 0.001). CONCLUSIONS: In this animal model,
      changes of intracardiac impedance revealed hemodynamic deterioration as reflected
      by EDV and EDP pressure. Thus, intracardiac impedance is a promising new
      application to monitor heart failure status within implantable devices.

PMID- 17553077
TI  - Heterogeneity of ventricular fibrillation dominant frequency during global
      ischemia in isolated rabbit hearts.
AB  - INTRODUCTION: Ventricular fibrillation (VF) studies show that ECG-dominant
      frequency (DF) decreases as ischemia develops. This study investigates the
      contribution of the principle ischemic metabolic components to this decline.
      METHODS AND RESULTS: Rabbit hearts were Langendorff-perfused at 40 mL/min with
      Tyrode's solution and loaded with RH237. Epicardial optical action potentials
      were recorded with a photodiode array (256 sites, 15 x 15 mm). After 60 seconds
      of VF (induced by burst pacing), global ischemia was produced by low flow (6
      mL/min), or the solution changed to impose hypoxia (95% N2/5% CO2), low pH(o)
      (6.7, 80% O2/20% CO2), or raised [K+](o) (8 mM). DF of the optical signals was
      determined at each site. Conduction velocity (CV), action potential duration
      (APD90), effective refractory period (ERP), activation threshold, dV/dt(max), and
      membrane potential were measured in separate experiments during ventricular
      pacing. During VF, ischemia decreased DF in the left ventricle (LV) (to [58 +/-
      6]%, P < 0.001), but not the right (RV) ([93 +/- 5]%). Raised [K+](o) reproduced
      this DF pattern (LV: [67 +/- 12]%, P < 0.001; RV: [95 +/- 9]%). LV DF remained
      elevated in hypoxia or low pH(o). During ventricular pacing, ischemia decreased
      CV in LV but not RV. Raised [K+](o) did not change CV in either ventricle.
      Ischemia and raised [K+](o) shortened APD90 without altering ERP. LV activation
      threshold increased in both ischemia and raised [K+](o) and was associated with
      diastolic depolarization and decreased dV/dt(max). CONCLUSIONS: These results
      suggest that during VF, decreased ECG DF in global ischemia is largely due to
      elevated [K+](o) affecting the activation thresholds in the LV rather than RV.

PMID- 17553078
TI  - Concordance study between the AmpFlSTR MiniFiler PCR amplification kit and
      conventional STR typing kits.
AB  - The AmpFlSTR MiniFiler polymerase chain reaction amplification kit developed by
      Applied Biosystems enables size reduction on eight of the larger STR loci
      amplified in the Identifiler kit, which will aid recovery of information from
      highly degraded DNA samples. The MiniFiler Kit amplifies CSF1PO, FGA, D2S1338,
      D7S820, D13S317, D16S539, D18S51, and D21S11 as well as the sex-typing locus
      amelogenin. A total of 1308 samples were evaluated with both the MiniFiler and
      Identifiler STR kits: 449 African American, 445 Caucasian, 207 Hispanic, and 207
      Asian individuals. Full concordance between Identifiler and MiniFiler Kits was
      observed in 99.7% (10,437 out of 10,464) STR allele calls compared. The 27
      differences seen are listed in Table 1 and encompass the loci D13S317 (n = 14)
      and D16S539 (n = 10) as well as D18S51 (n = 1), D7S820 (n = 1), and CSF1PO (n =
      1). Genotyping discrepancies between the Identifiler and MiniFiler kits were
      confirmed by reamplification of the samples and further testing using the
      PowerPlex 16 kit in many cases. DNA sequence analysis was also performed in order
      to understand the nature of the genetic variations causing the allele dropout or
      apparent repeat unit shift.

PMID- 17553079
TI  - Estimation of age-at-death for adult males using the acetabulum, applied to four
      Western European populations.
AB  - Methods to estimate adult age from observations of skeletal elements are not very
      accurate and motivate the development of better methods. In this article, we test
      recently published method based on the acetabulum and Bayesian inference,
      developed using Coimbra collection (Portugal). In this study, to evaluate its
      utility in other populations, this methodology was applied to 394 specimens from
      four different documented Western European collections. Four strategies of
      analysis to estimate age were outlined: (a) each series separately; (b) on Lisbon
      collection, taken as a reference Coimbra collection; (c) on Barcelona collection,
      taken as a reference both Portuguese collections; and (d) on London collection
      taken as reference the three Iberian collections combined. Results indicate that
      estimates are accurate (83-100%). As might be expected, the least accurate
      estimates were obtained when the most distant collection was used as a reference.
      Observations of the fused acetabulum can be used to make accurate estimates of
      age for adults of any age, with less accurate estimates when a more distant
      reference collection is used.

PMID- 17553080
TI  - Schizophrenia and suicide: a 10-year review of Kentucky medical examiner cases.
AB  - The risk of suicide is significantly increased in schizophrenics; it is estimated
      that 10-13% of individuals suffering from schizophrenia commit suicide.
      Schizophrenia is marked by psychotic exacerbations and remissions, with
      persistent deterioration in baseline functioning with each relapse. We present a
      10-year (1993-2002) retrospective review of Medical Examiners' cases of suicide
      of schizophrenic victims. Twenty-nine cases were between the ages of 20 and 75
      (mean age of 41.6 years). The majority of victims were male (62.1%) and Caucasian
      (86.2%). The leading method of suicide for both males and females was firearm
      injury (48.3%) mostly of the head, followed by overdose (20.7%), and hanging
      (13.8%). A comprehensive investigation of the biopsychosocial factors is
      warranted in cases of schizophrenics who commit suicide. This study offers an
      insightful analysis pertaining to the determination of intent in formulating the
      manner of death in this unique population.

PMID- 17553081
TI  - Efficiency evaluation of a police operation to fight the drug plague:
      distribution unit weight as an objective index.
AB  - Lod, a city near Tel-Aviv, is considered the main drug distribution center in
      Israel. A major police undercover operation in Lod, lasting close to a year, was
      terminated in May 2003. The success or failure of such an operation is frequently
      measured by the number of arrests made, the hierarchical level of the dealers
      arrested, the number of drug stations closed down, and the decrease in heroin
      seizures following the operation. In this work we suggest using an additional
      parameter, which has a scientific, objective basis, namely, comparing the changes
      in the average user weight unit ("dose") before and after the operation. We found
      that prior to the operation the average weight per unit was 1.1 g. Three months
      after the operation terminated the average weight per unit had decreased to 0.8 g
      and remained there for at least 4 months before rising again.

PMID- 17553082
TI  - Resolving paternity relationships using X-chromosome STRs and Bayesian networks.
AB  - X-chromosomal short tandem repeats (X-STRs) are very useful in complex paternity
      cases because they are inherited by male and female offspring in different ways.
      They complement autosomal STRs (as-STRs) allowing higher paternity probabilities
      to be attained. These probabilities are expressed in a likelihood ratio (LR). The
      formulae needed to calculate LR depend on the genotype combinations of suspected
      pedigrees. LR can also be obtained by the use of Bayesian networks (BNs). These
      are graphical representations of real situations that can be used to easily
      calculate complex probabilities. In the present work, two BNs are presented,
      which are designed to derive LRs for half-sisters/half-sisters and
      mother/daughter/paternal grandmother relationships. These networks were validated
      against known formulae and show themselves to be useful in other suspect pedigree
      situations than those for which they were developed. The BNs were applied in two
      paternity cases. The application of the mother/daughter/paternal grandmother BN
      highlighted the complementary value of X-STRs to as-STRs. The same case evaluated
      without the mother underlined that missing information tends to be conservative
      if the alleged father is the biological father and otherwise nonconservative. The
      half-sisters case shows a limitation of statistical interpretations in regard to
      high allelic frequencies.

PMID- 17553083
TI  - Acute fatal acetaminophen overdose without liver necrosis.
AB  - Two unusual cases of suicidal overdose of acetaminophen (paracetamol) without the
      usual extensive centrilobular necrosis of the liver are reported. Both cases were
      subjected to comprehensive drug screening by immunoassay, and a combination of
      gas chromatography with mass spectrometry, nitrogen detection, and electron
      capture detection. Acetaminophen was detected in both cases. No other drugs were
      detected in case #1, and only a small amount of olanzapine (<0.1 mg/L) was
      detected in case #2. No anatomical cause of death was identified in either case.
      If untreated, the normal outcome of a large acetaminophen overdose would be
      massive hepatic necrosis with delayed death and low blood and tissue
      acetaminophen concentrations. In contrast, particularly high postmortem
      acetaminophen concentrations were measured in both our cases with little hepatic
      tissue damage. For case #1, femoral blood acetaminophen 1280 mg/L, vitreous 878
      mg/L, and liver 729 mg/kg; in case #2, cardiac blood 1220 mg/L, vitreous 779
      mg/L, liver 3260 mg/kg, and gastric 11,500 mg/500 g. Acetaminophen was measured
      using high performance liquid chromatography with UV detection (254 nm) using 3
      hydroxyacetanilide as the internal standard. The very high concentrations of
      acetaminophen is these cases but relatively little hepatic damage suggests an
      alternative, possibly cardiac, mechanism of death.

PMID- 17553084
TI  - Fentanyl concentrations in 23 postmortem cases from the hennepin county medical
      examiner's office.
AB  - The purpose of this study was to compare blood fentanyl concentrations in
      fentanyl-related deaths with fentanyl concentrations found incidentally at
      autopsy, as well as with fentanyl concentrations found in hospitalized patients
      receiving fentanyl. Between the years 1997 to 2005, 23 fentanyl-positive
      postmortem cases were identified. Nineteen of 23 (82.6%) cases were deemed to be
      drug overdoses. Fentanyl alone was responsible for 8 of the 19 (42.1%) overdose
      deaths. Mean and median fentanyl concentrations were 36 (SD 38) microg/L and 22
      microg/L, respectively, range 5-120 microg/L. Seven of the cases were accidental,
      one undetermined. The remaining 11 of the 19 (57.9%) cases were mixed drug
      overdoses. Fentanyl concentrations in these cases were 31 (SD 46) microg/L, range
      5-152 microg/L. All of the mixed drug overdoses were determined to be accidental.
      Four cases where fentanyl was considered an incidental postmortem finding were
      determined to be natural deaths. In hospitalized inpatients (n = 11) receiving
      fentanyl 2 of the patients receiving fentanyl for chronic pain for more than 3
      months had concentrations of 8.5 microg/L and 9.9 microg/L. The other nine
      inpatient concentrations were less than 4 microg/L. In conclusion, blood fentanyl
      concentrations found in cases where fentanyl alone was determined to be the cause
      of death were similar to cases where fentanyl was part of a mixed drug overdose.
      There was also considerable overlap between fentanyl concentrations in fentanyl
      related overdose deaths compared to hospitalized patients being treated for
      chronic pain. Fentanyl concentrations in postmortem cases must be interpreted in
      the context of the deceased's past medical history and autopsy findings.

PMID- 17553085
TI  - Methyl 3-[3',4'-(methylenedioxy)phenyl]-2-methyl glycidate: an ecstasy precursor
      seized in Sydney, Australia.
AB  - Five 44 gallon drums labeled as glycidyl methacrylate were seized by the
      Australian Customs Service and the Australian Federal Police at Port Botany,
      Sydney, Australia, in December 2004. Each drum contained a white, semisolid
      substance that was initially suspected to be 3,4-methylenedioxymethylamphetamine
      (MDMA). Gas chromatography-mass spectroscopy (GC/MS) analysis demonstrated that
      the material was neither glycidyl methacrylate nor MDMA. Because intelligence
      sources employed by federal agents indicated that this material was in some way
      connected to MDMA production, suspicion fell on the various MDMA precursor
      chemicals. Using a number of techniques including proton nuclear magnetic
      resonance spectroscopy ((1)H NMR), carbon nuclear magnetic resonance spectroscopy
      ((13)C NMR), GC/MS, infrared spectroscopy, and total synthesis, the unknown
      substance was eventually identified as methyl 3-[3',4'(methylenedioxy)phenyl]-2
      methyl glycidate. The substance was also subjected to a published hydrolysis and
      decarboxylation procedure and gave a high yield of the MDMA precursor chemical,
      3,4-methylenedioxyphenyl-2-propanone, thereby establishing this material as a
      "precursor to a precursor."

PMID- 17553086
TI  - Characterization of the triacylglycerol crystal formation in adipose tissue
      during a vehicle collision.
AB  - The unusual appearance of crystalline fat structures was observed during the
      postmortem examination of a motor vehicle accident victim. The crystal structures
      were characterized using Fourier transform infrared spectroscopy and x-ray
      diffractometry. The structures were found to be made of triacylglycerols, a
      dominant lipid structure found in human adipose tissue, capable of forming
      various polymorphic structures. The morphology of the crystalline material was
      found using both techniques to be predominantly the beta' form of
      triacylglycerols. The accelerated growth of such triacylglycerol morphology has
      been observed as a result of shear stresses in other studies involving edible
      fats. As a result of the findings of this study, it is proposed that increased
      shear forces may be responsible for the formation of the unusual fat structure
      found in the victim. An understanding of the effect of forces on the structure of
      body fat in high-impact collisions can potentially assist in verifying a high
      velocity impact.

PMID- 17553087
TI  - A microfluidic device for presumptive testing of controlled substances.
AB  - A simple microfluidic device (MFD) has been developed to perform multiple color
      and crystal tests for controlled substance analysis. The MFD method uses less
      sample and reagents and generates less waste than traditional spot plate methods
      while performing several tests simultaneously. This methodology provides
      significantly more analytical information for a single sample analysis. The
      current generation device is the size of a microscope slide with four analytical
      channels: one for microcrystal tests and three for color tests. The optimized
      devices were subjected to a rigorous validation study using comparative replicate
      analyses and several operators. Target analytes were methamphetamine,
      amphetamine, cocaine, and oxycodone and color test reagents used were the
      Marquis, Simon, and cobalt thiocyanate. For the crystal tests, platinic chloride
      was used. The validation study showed the MFD's limits of detection to be in the
      picogram range. Positive tests results were observed in complex mixtures in which
      the controlled substance was present at concentrations of 5-10% (w/w). The
      microcrystal reagents showed greater sensitivity than color test reagents when
      used in the device. Reagent use and waste generation using the devices was 95%
      less that that used and generated using the traditional methods. The device
      performance was also shown to be operator independent.

PMID- 17553088
TI  - Infant death scene investigation and the assessment of potential risk factors for
      asphyxia: a review of 209 sudden unexpected infant deaths.
AB  - At the Wayne County Medical Examiner Office (WCMEO) in Detroit, Michigan, from
      2001 to 2004, thorough scene investigations were performed on 209 sudden and
      unexpected infant deaths, ages 3 days to 12 months. The 209 cases were reviewed
      to assess the position of the infant at the time of discovery and identify
      potential risk factors for asphyxia including bed sharing, witnessed overlay,
      wedging, strangulation, prone position, obstruction of the nose and mouth,
      coverage of the head by bedding and sleeping on a couch. Overall, one or more
      potential risk factors were identified in 178 of 209 cases (85.2%). The
      increasing awareness of infant positions at death has led to a dramatic reduction
      in the diagnosis of sudden infant death syndrome at the WCMEO. This study
      suggests that asphyxia plays a greater role in many sudden infant deaths than has
      been historically attributed to it.

PMID- 17553089
TI  - Four new illicit cocaine impurities from the oxidation of crude cocaine base:
      formation and characterization of the diastereomeric 2,3-dihydroxy-3
      phenylpropionylecgonine methyl esters from cis- and trans-cinnamoylcocaine.
AB  - Four new impurities have recently been detected in the gas chromatographic
      signature profiles of many illicit cocaine hydrochloride exhibits. These
      impurities are only seen in exhibits that have been oxidized and are most
      prominent in samples that have been highly oxidized. Exhibits containing these
      compounds were subjected to gas and liquid chromatographic-mass spectrometric
      analyses to determine the identity of the impurities. These impurities were
      subsequently synthesized to verify their structures. Four diastereomeric diols
      formed from the oxidation of cis- and trans-cinnamoylcocaine were characterized
      by nuclear magnetic resonance spectrometry, mass spectrometry, and synthesis.
      Oxidation of cis-cinnamoylcocaine in neutral conditions yielded (2R,3R)-dihydroxy
      3-phenylpropionylecgonine methyl ester and (2S,3S)-dihydroxy-3
      phenylpropionylecgonine methyl ester, while trans-cinnamoylcocaine produced
      (2R,3S)-dihydroxy-3-phenylpropionylecgonine methyl ester and (2S,3R)-dihydroxy-3
      phenylpropionylecgonine methyl ester. The recent appearance of these new
      impurities suggests that some illicit cocaine processors have modified their
      oxidation procedures of crude cocaine base for transformation into illicit
      refined cocaine hydrochloride.

PMID- 17553090
TI  - Virtual autopsy and forensic identification-practical application: a report of
      one case.
AB  - The body of an unidentified elderly woman was found trapped in a floodgate. Prior
      to autopsy, full-body multislice computed tomography (MSCT) was performed for
      study of bone lesions and cause of death. Age was estimated by analysis of the
      sternal end of the fourth rib and of the pubic symphyseal medial articular
      surfaces. The results were then compared with the autopsy findings. MSCT was
      superior to autopsy in diagnosis of traumatic bone lesions and also revealed
      dental anomalies and signs of drowning. Age estimation gave a similar result for
      both methods. This case report illustrates the potential value of MSCT for medico
      legal investigations of death: diagnosis of injuries, possibility of determining
      the cause of death, and anthropological study in order to estimate age or to
      visualize features likely to enable identification of a corpse.

PMID- 17553091
TI  - Heat induced changes to dental resin composites: a reference in forensic
      investigations?
AB  - The objective was to investigate color change and surface damage in dental resin
      composites exposed to high temperatures over different time intervals for
      comparative purposes. Samples were prepared using two resins - Z100(R) (R1) and
      Charisma (R2), heated at the following temperatures: 200 degrees C, 400 degrees
      C, 600 degrees C, 1000 degrees C, for 15, 30 and 45 min (n = 104 for each resin
      sample). Color (DeltaE) and brightness (DeltaL) changes were analyzed by
      spectrophotometry using the CIE Lab system and surface changes by Scanning
      Electron Microscopy (SEM). R1 showed more intense color changes after heat
      exposure than R2. DeltaL values were found to be the best parameter for
      evaluation of light and color change. A biphasic pattern after thermal exposure
      was detected, from dark brown to light white. SEM showed more intense alterations
      in R2 than in R1. These results indicate that the parameters observed in both
      resins are useful as a guide in forensic analyses.

PMID- 17553092
TI  - A rape case solved by mitochondrial DNA mixture analysis.
AB  - In cases of stains that contain mixed DNA from different contributors, analyzing
      mitochondrial DNA (mtDNA) requires the use of cloning techniques. We developed an
      efficient cloning technique that was applied in a rape case. After a differential
      lysis-based DNA extraction from vaginal swabs, hypervariable region I and II
      (HVI, HVII) amplicons obtained from the male fraction were cloned. Although we
      mainly found the victim's haplotype, we were able to detect the suspect's
      haplotype in two clones for HVI and in one clone for HVII. As the midpiece of the
      flagellum, which contains mitochondria, can be lost during the differential
      lysis, we also investigated the female fraction by cloning to evaluate the
      proportion of victim/suspect mtDNA. Unfortunately, only clones presenting the
      victim's haplotype were found. This case highlights the need for an optimal
      differential lysis protocol to enrich the male fraction not only with nuclear but
      also mitochondrial DNA.

PMID- 17553093
TI  - Mental health service recipients and prison work release: how do the mentally ill
      fare compared to other inmates in prison work release programs?
AB  - The objective of this study was to compare the success rate of the mentally ill
      and other inmates on prison work release within gender groups. Mentally ill (MI)
      men (n = 42) had a higher success rate (79%) than other men (NMI) (61%) (n = 49),
      but this difference only approached statistical significance (p = 0.07), and
      mental illness did not distinguish male success/failures in regression analyses.
      Mentally ill women (n = 51) had a statistically significant lower success rate
      (58%) than other women inmates (n = 49) (83%) on work release. The difference in
      rates, however, only occurred in the group of women who were currently in prison
      due to a parole violation, not new court commitments. Regression analysis
      confirmed the importance of mental illness and current commitment as a parole
      violator. A greater number of MI men should be allowed to participate in work
      release. Women with mental health issues who had prior trouble on parole may need
      enhanced services.

PMID- 17553095
TI  - Simplified low-copy-number DNA analysis by post-PCR purification.
AB  - Frequently, evidentiary items contain an insufficient quantity of DNA to obtain
      complete or even partial DNA profiles using standard forensic gentotyping
      techniques. Such low-copy-number (LCN) samples are usually subjected to increased
      amplification cylces to obtain genetic data. In this study, a 28-cycle polymerase
      chain reaction (PCR) was used to evaluate various methods of post-PCR
      purification for their effects on the sensitivity of fluorophore-based allelic
      detection subsequent to capillary electrophoretic separation. The amplified
      product was purified using filtration, silica gel membrane, and enzyme mediated
      hydrolysis purification techniques and evaluated for their effect on fluorescent
      allelic signal intensity. A purification method was selected and its effect on
      fluorescent allelic signal intensity was compared with that of the unpurified PCR
      product. A method of post-PCR purification is described which increases the
      sensitivity of standard 28-cycle PCR such that profiles from LCN DNA templates
      (<100 pg DNA) can be obtained. Full DNA profiles were consistently obtained with
      as little as 20 pg template DNA without increased cycle number. In mock case type
      samples with dermal ridge fingerprints, genetic profiles were obtained by
      amplification with 28 cycles followed by post-PCR purification whereas no
      profiles were obtained without purification of the PCR product. Allele dropout,
      increased stutter, and sporadic contamination typical of LCN analysis were
      observed; however, no contamination was observed in negative amplification
      controls. Post-PCR purification of the PCR product can increase the sensitivity
      of capillary electrophoresis to such an extent that DNA profiles can be obtained
      from <100 pg of DNA using 28-cycle amplification.

PMID- 17553096
TI  - Validation of LAB color mode as a nondestructive method to differentiate black
      ballpoint pen inks.
AB  - Nondestructive digital processing methods such as lab color mode (available in
      Adobe Photoshop) are emerging as alternative methods for forensic document
      examiners to use when attempting to differentiate writing instrument inks.
      Although these techniques appear to be viable, little data currently exists
      regarding the known or potential error rates associated with these techniques.
      Without adequate data, the validity and reliability of these techniques,
      including lab color, can not be established. In an attempt to begin to address
      these issues, 44 black ballpoint ink pens were obtained and used to create 990
      pen-pair samples for analysis using established lab color mode techniques. No
      erroneous findings of "different" were reported following the examination of the
      known pen-pair combinations in which the same pen was used to create the samples
      (n = 44). Of the remaining 946 samples, 737 pen-pair samples were differentiated
      using the lab color mode method, while 209 samples were unable to be
      differentiated and were recorded as either being "similar" (n = 153) or "unsure"
      (n = 56). Comparison of the lab color mode results with the results obtained
      through additional testing using traditional infrared reflectance and infrared
      luminescence test methods showed that lab color differentiated 102 pen-pair
      samples (11%; 102/946) that were not differentiated using a VSC-4C.

PMID- 17553097
TI  - Forensic DNA analysis on microfluidic devices: a review.
AB  - The advent of microfluidic technology for genetic analysis has begun to impact
      forensic science. Recent advances in microfluidic separation of short-tandem
      repeat (STR) fragments has provided unprecedented potential for improving speed
      and efficiency of DNA typing. In addition, the analytical processes associated
      with sample preparation--which include cell sorting, DNA extraction, DNA
      quantitation, and DNA amplification--can all be integrated with the STR
      separation in a seamless manner. The current state of these microfluidic methods
      as well as their advantages and potential shortcomings are detailed. Recent
      advances in microfluidic device technology, as they pertain to forensic DNA
      typing, are discussed with a focus on the forensic community.

PMID- 17553098
TI  - Expression of beta-keratin mRNAs and proline uptake in epidermal cells of growing
      scales and pad lamellae of gecko lizards.
AB  - Beta-keratins form a large part of the proteins contained in the hard beta layer
      of reptilian scales. The expression of genes encoding glycine-proline-rich beta
      keratins in normal and regenerating epidermis of two species of gecko lizards has
      been studied by in situ hybridization. The probes localize mRNAs in
      differentiating oberhautchen and beta cells of growing scales and in modified
      scales, termed pad lamellae, on the digits of gecko lizards. In situ localization
      at the ultrastructural level shows clusters of gold particles in the cytoplasm
      among beta-keratin filaments of oberhautchen and beta cells. They are also
      present in the differentiating elongation or setae of oberhautchen cells present
      in pad lamellae. Setae allow geckos to adhere and climb vertical surfaces.
      Oberhautchen and beta cells also incorporate tritiated proline. The fine
      localization of the beta-keratin mRNAs and the uptake of proline confirms the
      biomolecular data that identified glycine-proline-rich beta-keratin in
      differentiating beta cells of gecko epidermis. The present study also shows the
      presence of differentiating and metabolically active cells in both inner and
      outer oberhautchen/beta cells at the base of the outer setae localized at the tip
      of pad lamellae. The addition of new beta and alpha cells to the corneous layer
      near the tip of the outer setae explains the anterior movement of the setae along
      the apical free-margin of pad lamellae. The rapid replacement of setae ensures
      the continuous usage of the gecko's adhesive devices, the pad lamellae, during
      most of their active life.

PMID- 17553099
TI  - Computational mouse atlases and their application to automatic assessment of
      craniofacial dysmorphology caused by the Crouzon mutation Fgfr2(C342Y).
AB  - Crouzon syndrome is characterized by premature fusion of sutures and
      synchondroses. Recently, the first mouse model of the syndrome was generated,
      having the mutation Cys342Tyr in Fgfr2c, equivalent to the most common human
      Crouzon/Pfeiffer syndrome mutation. In this study, a set of micro-computed
      tomography (CT) scannings of the skulls of wild-type mice and Crouzon mice were
      analysed with respect to the dysmorphology caused by Crouzon syndrome. A
      computational craniofacial atlas was built automatically from the set of wild
      type mouse micro-CT volumes using (1) affine and (2) non-rigid image
      registration. Subsequently, the atlas was deformed to match each subject from the
      two groups of mice. The accuracy of these registrations was measured by a
      comparison of manually placed landmarks from two different observers and
      automatically assessed landmarks. Both of the automatic approaches were within
      the interobserver accuracy for normal specimens, and the non-rigid approach was
      within the interobserver accuracy for the Crouzon specimens. Four linear
      measurements, skull length, height and width and interorbital distance, were
      carried out automatically using the two different approaches. Both automatic
      approaches assessed the skull length, width and height accurately for both groups
      of mice. The non-rigid approach measured the interorbital distance accurately for
      both groups while the affine approach failed to assess this parameter for both
      groups. Using the full capability of the non-rigid approach, local displacements
      obtained when registering the non-rigid wild-type atlas to a non-rigid Crouzon
      mouse atlas were determined on the surface of the wild-type atlas. This revealed
      a 0.6-mm bending in the nasal region and a 0.8-mm shortening of the zygoma, which
      are similar to characteristics previously reported in humans. The most striking
      finding of this analysis was an angulation of approximately 0.6 mm of the cranial
      base, which has not been reported in humans. Comparing the two different
      methodologies, it is concluded that the non-rigid approach is the best way to
      assess linear skull parameters automatically. Furthermore, the non-rigid approach
      is essential when it comes to analysing local, non-linear shape differences.

PMID- 17553101
TI  - Postcranial skeletal pneumaticity: a case study in the use of quantitative
      microCT to assess vertebral structure in birds.
AB  - Limb elements in birds have been characterized as exhibiting a reduction in
      trabecular bone, thinner cortices and decreased bending strength when
      pneumatized, yet it is unclear if these characteristics generalize to the axial
      skeleton. Thin section techniques, the traditional gold standard for bone
      structure studies, have most commonly been applied to the study of avian bone.
      This destructive technique, however, makes it subsequently impossible to use the
      same samples in experimental testing systems that allow researchers to correlate
      structure with the mechanical properties of the bone. Micro-computed tomography
      (microCT), a non-destructive X-ray imaging technique, can be used to assess the
      effect of pneumatization on vertebral cortical and trabecular bone through
      virtual extraction and structural quantification of each tissue type. We
      conducted a preliminary investigation of the application of microCT methods to
      the study of cortical and trabecular bone structure in a small sample of
      pneumatic and apneumatic thoracic vertebrae. The sample consisted of two similar
      sized anatids, Aix sponsa (n = 7) and Oxyura jamaicensis (n = 5). Volumes of
      interest were created that contoured (outlined) the boundaries of the ventral
      cortical bone shell, the trabecular compartment and the whole centrum (cortical
      bone + trabecular bone), and allowed independent structural analysis of each
      volume of interest. Results indicated that bone volume fraction of the whole
      centrum was significantly higher in the apneumatic O. jamaicensis than in the
      pneumatized A. sponsa (A. sponsa = 36%, O. jamaicensis = 48%, P < 0.05). In
      contrast, trabecular bone volume fraction was similar between the two species.
      The ventral cortical bone shell was approximately 23% thinner (P < 0.05) in A.
      sponsa (0.133 mm) compared with apneumatic O. jamaicensis (0.172 mm). This case
      study demonstrates that microCT is a powerful non-destructive imaging technique
      that may be applied to the three-dimensional study of avian bone. The preliminary
      results suggest that pneumatic and apneumatic vertebrae of comparably sized avian
      species differ in relative bone volume, with the largest difference apparent at
      the level of the cortex, and not within trabecular bone. The presence of
      relatively thin cortices in pneumatic vertebrae is consistent with previous
      studies contrasting diaphyseal cortical bone between pneumatic and apneumatic
      long bones. Methodological issues related to this and any comparative microCT
      study of bone structure are discussed.

PMID- 17553100
TI  - Slit-Robo interactions during cortical development.
AB  - Interneurons are an integral part of cortical neuronal circuits. During the past
      decade, numerous studies have shown that these cells, unlike their pyramidal
      counterparts that are derived from the neuroepithelium along the lumen of the
      lateral ventricles, are generated in the ganglionic eminences in the subpallium.
      They use tangential migratory paths to reach the cortex, guided by intrinsic and
      extrinsic cues. Evidence is now emerging which suggests that the family of Slit
      proteins, acting through Robo receptors, play a role not only in axon guidance in
      the developing forebrain, but also as guiding signals in the migration of
      cortical interneurons. Here we describe the patterns of expression of Slit and
      Robo at different stages of forebrain development and review the evidence in
      support of their role in cortical interneuron migration. Slit-Robo signal
      transduction mechanisms are also important during normal development in a number
      of systems in the body and in disease states, making them potential therapeutic
      targets for the treatment of neurological disorders and certain types of cancer.

PMID- 17553102
TI  - Alpha-synuclein pathology in the olfactory pathways of dementia patients.
AB  - Lewy-type pathology is a characteristic of a number of neurodegenerative
      disorders, including Parkinson's disease and dementia with Lewy bodies. Thus far,
      the definitive diagnosis of these dementias can only be confirmed at post-mortem.
      However, it is known that the loss of smell (anosmia) is an early symptom in
      patients who develop dementia, and the use of the smell test has been proposed as
      an early diagnostic procedure. The aim of this study was to understand further
      the extent of Lewy pathology in the olfactory system of patients with
      neurodegenerative disorders. Post-mortem tissue from 250 subjects was obtained
      from the OPTIMA brain bank. Five areas of the olfactory pathway were examined by
      immunolabelling for alpha-synuclein - a major component of Lewy pathology: the
      olfactory tract/bulb (n = 79), the anterior olfactory nucleus in the lateral
      olfactory gyrus (n = 193), the region of olfactory projection to the orbito
      frontal cortex (n = 225), the hippocampus (n = 236) and the amygdala (n = 201).
      Results show that Lewy pathology affects different parts of the olfactory
      pathways differentially, suggesting a specific pattern of development of
      pathology. Clinical Parkinson's disease is most likely to be identified if the
      orbito-frontal cortex is affected, while the diagnosis is less likely if the
      pathology is restricted to the olfactory bulb or tract. These results suggest
      that pathology in the olfactory bulb and tract occurs prior to clinical signs of
      Parkinson's disease. Furthermore, the results presented here provide further
      evidence supporting the possible value of a smell test to aid the clinical
      diagnosis of neurodegenerative diseases.

PMID- 17553104
TI  - The anatomy of the cardiac veins in mice.
AB  - Although the cardiac coronary system in mice has been the studied in detail by
      many research laboratories, knowledge of the cardiac veins remains poor. This is
      because of the difficulty in marking the venous system with a technique that
      would allow visualization of these large vessels with thin walls. Here we present
      the visualization of the coronary venous system by perfusion of latex dye through
      the right caudal vein. Latex injected intravenously does not penetrate into the
      capillary system. Murine cardiac veins consist of several principal branches
      (with large diameters), the distal parts of which are located in the
      subepicardium. We have described the major branches of the left atrial veins, the
      vein of the left ventricle, the caudal veins, the vein of the right ventricle and
      the conal veins forming the conal venous circle or the prepulmonary conal venous
      arch running around the conus of the right ventricle. The venous system of the
      heart drains the blood to the coronary sinus (the left cranial caval vein) to the
      right atrium or to the right cranial caval vein. Systemic veins such as the left
      cranial caval, the right cranial caval and the caudal vein open to the right
      atrium. Knowledge of cardiac vein location may help to elucidate abnormal vein
      patterns in certain genetic malformations.

PMID- 17553103
TI  - Functional respiratory morphology in the newborn quokka wallaby (Setonix
      brachyurus).
AB  - A morphological and morphometric study of the lung of the newborn quokka wallaby
      (Setonix brachyurus) was undertaken to assess its morphofunctional status at
      birth. Additionally, skin structure and morphometry were investigated to assess
      the possibility of cutaneous gas exchange. The lung was at canalicular stage and
      comprised a few conducting airways and a parenchyma of thick-walled tubules lined
      by stretches of cuboidal pneumocytes alternating with squamous epithelium, with
      occasional portions of thin blood-gas barrier. The tubules were separated by
      abundant intertubular mesenchyme, aggregations of developing capillaries and
      mesenchymal cells. Conversion of the cuboidal pneumocytes to type I cells
      occurred through cell broadening and lamellar body extrusion. Superfluous
      cuboidal cells were lost through apoptosis and subsequent clearance by alveolar
      macrophages. The establishment of the thin blood-gas barrier was established
      through apposition of the incipient capillaries to the formative thin squamous
      epithelium. The absolute volume of the lung was 0.02 +/- 0.001 cm(3) with an air
      space surface area of 4.85 +/- 0.43 cm(2). Differentiated type I pneumocytes
      covered 78% of the tubular surface, the rest 22% going to long stretches of type
      II cells, their precursors or low cuboidal transitory cells with sparse lamellar
      bodies. The body weight-related diffusion capacity was 2.52 +/- 0.56 mL O(2) min(
      1) kg(-1). The epidermis was poorly developed, and measured 29.97 +/- 4.88 microm
      in thickness, 13% of which was taken by a thin layer of stratum corneum,
      measuring 4.87 +/- 0.98 microm thick. Superficial capillaries were closely
      associated with the epidermis, showing the possibility that the skin also
      participated in some gaseous exchange. Qualitatively, the neonate quokka lung had
      the basic constituents for gas exchange but was quantitatively inadequate,
      implying the significance of percutaneous gas exchange.

PMID- 17553105
TI  - High-lysine corn generated by endosperm-specific suppression of lysine catabolism
      using RNAi.
AB  - Because of the limited lysine content in corn grain, synthetic lysine supplements
      are added to corn meal-based rations for animal feed. The development of
      biotechnology, combined with the understanding of plant lysine metabolism,
      provides an alternative solution for increasing corn lysine content through
      genetic engineering. Here, we report that by suppressing lysine catabolism,
      transgenic maize kernels accumulated a significant amount of lysine. This was
      achieved by RNA interference (RNAi) through the endosperm-specific expression of
      an inverted-repeat (IR) sequence targeting the maize bifunctional lysine
      degradation enzyme, lysine-ketoglutarate reductase/saccharopine dehydrogenase
      (ZLKR/SDH). Although plant-short interfering RNA (siRNA) were reported to lack
      tissue specificity due to systemic spreading, we confirmed that the suppression
      of ZLKR/SDH in developing transgenic kernels was restricted to endosperm tissue.
      Furthermore, results from our cloning and sequencing of siRNA suggested the
      absence of transitive RNAi. These results support the practical use of RNAi for
      plant genetic engineering to specifically target gene suppression in desired
      tissues without eliciting systemic spreading and the transitive nature of plant
      RNAi silencing.

PMID- 17553106
TI  - Evaluating complex interventions.

PMID- 17553107
TI  - Evidence in the palm of your hand: development of an outcomes-focused knowledge
      translation intervention.
AB  - AIM: The aim of the project was to develop an electronic information gathering
      and dissemination system to support both nursing-sensitive outcomes data
      collection and evidence-based decision-making at the point-of-patient care.
      BACKGROUND: With the current explosion of health-related knowledge, it is a
      challenge for nurses to regularly access information that is most current. The
      Internet provides timely access to health information, however, nurses do not
      readily use the Internet to access practice information because of being task
      driven and coping with heavy workloads. Mobile computing technology addresses
      this reality by providing the opportunity for nurses to access relevant
      information at the time of nurse-patient contact. METHOD: A cross-sectional,
      mixed-method design was used to describe nurses' requirements for point-of-care
      information collection and utilization. The sample consisted of 51 nurses from
      hospital and home care settings. Data collection involved work sampling and focus
      group interviews. FINDINGS: In the hospital sector, 40% of written information
      was recorded onto "personal papers" at point-of-care and later transcribed into
      the clinical record. Nurses often sought information away from the point-of-care;
      for example, centrally located health records, or policy and procedure manuals.
      In home care, documentation took place in clients' homes. The most frequent
      source of information was "nurse colleagues." Nurses' top priorities for
      information were vital signs data, information on intravenous (IV) drug
      compatibility, drug references, and manuals of policies and procedures.
      IMPLICATIONS: A prototype software system was designed that enables nurses to use
      handheld computers to simultaneously document patients' responses to treatment,
      obtain real-time feedback about patient outcomes, and access electronic resources
      to support clinical decision-making. CONCLUSION: The prototype software system
      has the potential to increase nurses' access to patient outcomes information and
      evidence for point-of-care decision-making.

PMID- 17553108
TI  - Integrated care for older people: methodological issues in conducting a
      systematic literature review.
AB  - INTRODUCTION: Systematic reviews are a useful approach for nurses to take in
      exploring issues important to their practice, and in this article the process of
      conducting a systematic literature review on integrated care for older people is
      described. The review was conducted as one strand of a research project aiming to
      inform the development of locality-based integrated care for older people in
      Northern Ireland, a development driven by observations of user needs.
      METHODOLOGY: Systematic literature review methodology is summarized and
      critiqued. The process of undertaking the review in this study is described with
      a focus on the first stage of identifying literature, and the challenges that
      this presents in a review which draws on multiple bodies of work. RESULTS:
      Producing a systematic literature review in integrated care is a complex
      undertaking, comprising a variety of different sectors, organizations, care
      settings, professionals, and other users, with their own bodies of knowledge; the
      need for an inclusive approach; the need to search a wide range of databases;
      nonspecific terminology; and the inappropriateness of study design hierarchies as
      selection criteria. CONCLUSIONS: While such a literature review might provide a
      basis for research and practice, the ability of the review team to call upon a
      wide range of skills, experience, and knowledge across the information management
      field and the care system is crucial.

PMID- 17553109
TI  - Clinical nurse specialists' use of evidence in practice: a pilot study.
AB  - BACKGROUND: The interest in finding ways to bridge the gap between nursing
      research and implementation of findings into practice has been increasing.
      Clinical nurse specialists (CNSs) may be a bridge between frontline nurses and
      current developments in practice. While several researchers have studied the use
      of evidence by nurses in general, no known studies have been focused specifically
      on the use of evidence by CNSs. PURPOSE: The purpose of this pilot study was to
      develop an understanding of the sources, nature, and application of evidence used
      by CNSs in practice and to investigate the feasibility of conducting a
      qualitative study focused on the CNS role in relation to evidence use in
      practice. METHODS: This pilot study is a descriptive exploratory design in the
      qualitative paradigm. Seven CNSs from a large Western Canadian health region were
      interviewed. Interview transcripts were reviewed for recurrent themes about
      sources of evidence, evidence use, and barriers and facilitators to evidence use.
      FINDINGS: CNSs access and use evidence from a variety of sources. All CNSs
      indicated that research literature was a primary source of evidence and research
      was used in decision-making. Peers and experience were also important sources of
      evidence. CNSs used the Internet extensively to consult research databases,
      online sources of evidence, and to contact peers about current practice. CNSs
      also gathered evidence from frontline nurses, healthcare team members, and
      families before decision-making. The choice of evidence often depended upon the
      type of question they were attempting to answer. Barriers cited by CNSs support
      previous research and included lack of time, resources, and receptivity at
      clinical and organizational levels. Facilitators included peers, organizational
      support, and advanced education. DISCUSSION: CNSs in Canada have advanced
      education and clinical expertise and many are employed in roles that permeate
      organizational management and clinical nursing care. It is suggested that
      qualitative research in naturalized settings that investigates the role of CNSs
      in relation to the dissemination of evidence in nursing practice needs attention.

PMID- 17553110
TI  - Postnatal debriefing interventions to prevent maternal mental health problems
      after birth: exploring the gap between the evidence and UK policy and practice.
AB  - BACKGROUND: Postnatal mental health problems range from transient psychological
      problems to depression, anxiety, psychosis, and post-traumatic stress disorder
      (PTSD). Debriefing is a structured psychological intervention to prevent
      postnatal psychological problems, particularly PTSD and depression. Many UK
      maternity service providers have established postnatal debriefing services, in
      some cases supported by policy, despite a lack of robust evidence. In this
      article, current evidence of the effectiveness of postnatal debriefing and the
      availability and current provision of debriefing offered in UK maternity services
      is described. METHODS: A structured literature review was undertaken. FINDINGS:
      Eight randomized controlled trials were conducted to evaluate debriefing or
      counseling interventions in childbirth settings, and seven studies were done to
      evaluate debriefing or counseling interventions provided within UK maternity
      services or describe the availability of such services. Results of six RCTs were
      that no differences in outcomes were found, one report indicated possible harm
      from debriefing, and two indicated a positive association related to a
      psychological intervention. Methodological issues might account for differing
      trial outcomes. No standard intervention was used in any RCTs or service
      interventions. Confusion apparently exists in use of the term "debriefing" in UK
      maternity service policy and practice. Although service evaluations showed that
      women valued opportunities to discuss their birth, evidence to support the
      content and timing of service provision and effectiveness of this was lacking.
      DISCUSSION: It might be appropriate to consider offering women an opportunity to
      discuss their childbirth experience and to differentiate this discussion from the
      offer of a formal debriefing, which is unsupported by evidence. IMPLICATIONS FOR
      PRACTICE/CONCLUSION: Midwives and other health care professionals who provide
      opportunities for women to talk about childbirth should be clear about terms used
      to describe the intervention, as well as the purpose and content of this.
      Differentiating between women who perceive their experience of childbirth as
      traumatic and those who develop symptoms of PTSD (for whom specific treatment may
      be required) is important. All health care professionals should be aware of the
      signs and symptoms of mental health problems after birth, which may include
      depression, anxiety, or psychosis in addition to PTSD.

PMID- 17553111
TI  - Teaching EBP: part 1. Making sense of clinical practice guidelines.

PMID- 17553112
TI  - New knowledge discussion groups: counteracting the common barriers to evidence
      based practice.

PMID- 17553115
TI  - The light stress-induced protein ELIP2 is a regulator of chlorophyll synthesis in
      Arabidopsis thaliana.
AB  - The early light-induced proteins (ELIPs) belong to the multigenic family of
      pigment-binding light-harvesting complexes. ELIPs accumulate transiently and are
      believed to play a protective role in plants exposed to high levels of light.
      Constitutive expression of the ELIP2 gene in Arabidopsis resulted in a marked
      reduction of the pigment content of the chloroplasts, both in mature leaves and
      during greening of etiolated seedlings. The chlorophyll loss was associated with
      a decrease in the number of photosystems in the thylakoid membranes, but the
      photosystems present were fully assembled and functional. A detailed analysis of
      the chlorophyll-synthesizing pathway indicated that ELIP2 accumulation
      downregulated the level and activity of two important regulatory steps: 5
      aminolevulinate synthesis and Mg-protoporphyrin IX (Mg-Proto IX) chelatase
      activity. The contents of glutamyl tRNA reductase and Mg chelatase subunits CHLH
      and CHLI were lowered in response to ELIP2 accumulation. In contrast,
      ferrochelatase activity was not affected and the inhibition of Heme synthesis was
      null or very moderate. As a result of reduced metabolic flow from 5
      aminolevulinic acid, the steady state levels of various chlorophyll precursors
      (from protoporphyrin IX to protochlorophyllide) were strongly reduced in the
      ELIP2 overexpressors. Taken together, our results indicate that the physiological
      function of ELIPs could be related to the regulation of chlorophyll concentration
      in thylakoids. This seems to occur through an inhibition of the entire
      chlorophyll biosynthesis pathway from the initial precursor of tetrapyrroles, 5
      aminolevulinic acid. We suggest that ELIPs work as chlorophyll sensors that
      modulate chlorophyll synthesis to prevent accumulation of free chlorophyll, and
      hence prevent photooxidative stress.

PMID- 17553117
TI  - Diagnostic inaccuracy in children referred with "first seizure": role for a first
      seizure clinic.
AB  - PURPOSE: To determine (a) the range of diagnoses, and (b) the prevalence of
      previous seizures in children presenting to a first seizure clinic. METHODS: One
      hundred twenty-seven children were seen in a tertiary care First Seizure Clinic.
      Inclusion criteria were age 1 month-17 years with an unprovoked event suggestive
      of seizure. Data collected included referring physician specialty, child's age,
      gender, developmental status, and clinical diagnosis of epileptologist
      (nonepileptic vs. epileptic). For those with epileptic events, seizure type,
      syndrome (if identifiable), presumed etiology (idiopathic, cryptogenic, and
      symptomatic), presence of prior afebrile and febrile seizures, provoking factors,
      family history, pre/perinatal complications and EEG results were recorded.
      RESULTS: The diagnosis was epileptic in 94 (74%), nonepileptic in 31 (24%) and
      unclassifiable in two (2%). Pediatricians were more likely to refer true
      epileptic events (92%) than ED physicians (76%) or family physicians (65%). Mean
      age at presentation was 8 years. Fifteen percent of children were developmentally
      delayed and neurological examination was abnormal in 11%. For those diagnosed
      with epileptic events, 32 presented with generalized while 62 presented with
      partial onset seizures. An epilepsy syndrome was identifiable in 15 cases. Thirty
      eight percent experienced a prior probable seizure which was recognized by the
      referring physician in only one case. An EEG was done in all children with
      seizures and was abnormal in 41%. Early EEG was performed in 20% of children and
      did not show statistical significance. CONCLUSIONS: Diagnostic inaccuracy is
      common in first seizure. One quarter of children were incorrectly diagnosed as
      having a seizure while the diagnosis of epilepsy was missed in over one-third of
      children.

PMID- 17553118
TI  - New statistical method for analyzing time to first seizure: example using data
      comparing carbamazepine and valproate monotherapy.
AB  - INTRODUCTION: Time to first seizure is a common outcome in antiepileptic drug
      (AED) studies. Previous studies have typically failed to find statistically
      significant differences between carbamazepine (CBZ) and valproate (VPS). We re
      analyzed a meta-analysis comparing CBZ and VPS monotherapy with new powerful
      statistical methods that incorporate baseline seizure rate information. METHODS:
      Individual patient data were available on 1,265 patients from a meta-analysis of
      five trials. The outcome measure was time to first seizure after randomization,
      adjusted for background variables and baseline seizure rate. RESULTS: We found
      strong evidence of an interaction between treatment and epilepsy type, and
      between treatment and age. For generalized onset seizures, VPS was statistically
      significantly better than CBZ: VPS delayed the first seizure after treatment 58%,
      52%, 44%, and 36% longer than CBZ for individuals aged 10, 20, 30, or 40,
      respectively. For partial onset seizures in individuals older than 30, CBZ was
      significantly better then VPS; CBZ delayed the time to first seizure by 9%, 25%,
      44%, and 66% longer than VPS for individuals aged 20, 30, 40, or 50,
      respectively. CONCLUSION: The results show clear age-varying differences between
      the effectiveness of CBZ and VPS for generalized onset and partial onset
      seizures, which have not been identified in previous studies using standard
      statistical methods. In future trials of AED monotherapy or add-on where time to
      first or Nth seizure is an outcome, methodology that can incorporate baseline
      seizure rate information would allow more powerful comparisons between treatments
      or between treatment and placebo.

PMID- 17553119
TI  - Brain mapping of epileptic activity in a case of idiopathic occipital lobe
      epilepsy (Panayiotopoulos syndrome).
AB  - The Panayiotopoulos type of occipital lobe epilepsy has generated great interest,
      but the particular brain areas involved in the peculiar seizure manifestations
      have not been established. We studied a patient with the syndrome, using high
      resolution EEG and simultaneous EEG and functional magnetic resonance imaging
      (fMRI). Resolution of the scalp EEG was improved using a realistic spline
      Laplacian algorithm, and produced a complex distribution of current sinks and
      sources over the occipital lobe. The spike-related blood oxygen level dependent
      (BOLD) effect was multifocal, with clusters in lateral and inferior occipital
      lobe and lateral and anterior temporal lobe. We also performed regional dipole
      seeding in BOLD clusters to determine their relative contribution to generation
      of scalp spikes. The integrated model of the neurophysiologic and vascular data
      strongly suggests that the epileptic activity originates in the lateral occipital
      area, spreading to the occipital pole and lateral temporal lobe.

PMID- 17553120
TI  - Focal chronic inflammatory epileptic encephalopathy in a patient with
      malformations of cortical development, with a review of the spectrum of chronic
      inflammatory epileptic encephalopathy.
AB  - PURPOSE: Chronic cellular inflammation closely associated with epilepsy without
      an active infection is a hallmark of Rasmussen encephalitis (RE). RE has typical
      and defining features lacking in other rare epilepsy patients who also have
      neocortical lymphocytes without an identifiable cause. A patient with
      malformations of cortical development had an abrupt change in frequency and
      epileptic focus after 22 years of a stable seizure disorder. Functional
      neurosurgery yielded a specimen showing a mixed cellular meningoencephalitis in
      the absence of a demonstrable infection. METHODS: Historical, neurologic,
      electroencephalographic, pathologic, and literature data were correlated.
      RESULTS: There was a subarachnoid mixed infiltrate including evidence of
      dendritic cells in our patient and also cytotoxic T lymphocytes adjacent to
      karyolytic neurons that corresponded to cells previously demonstrated to damage
      neurons in RE. Literature review disclosed 42 other cases similar to RE but with
      heterogeneous findings. The course was more protracted and often more benign than
      in RE. The inflammation that would have markedly decreased or disappeared in RE
      over that period was generally still well represented. CONCLUSIONS: Our patient
      has heterogeneous features similar to, yet with differences from, RE. Literature
      review of chronic cellular inflammatory epileptic encephalopathy cases also
      similar to RE discloses important differences that may reflect idiosyncratic
      reactions and pace of the disease rather than a different disease. Comorbidity
      factors, genetic population traits, and secondary effects of the seizure disorder
      may lead to an expansion of the initial site of damage by an autoimmune reaction.
      These cases might best be grouped, probably along with RE, as secondary
      autoimmune diseases.

PMID- 17553121
TI  - Severe epilepsy in X-linked creatine transporter defect (CRTR-D).
AB  - Disorders of creatine synthesis or its transporter resulting in neurological
      impairment with mental retardation and epilepsy have only been recognized in
      recent years. To date, the epileptic disorder observed in creatine transporter
      deficiency (CRTR-D) has been described as a mild phenotype with infrequent
      seizures and favorable response to common antiepileptic drugs. We report on a 5
      year-old boy with known speech delay who presented with severe and refractory
      epilepsy. After extensive investigations, metabolite analysis and brain 1H-MRS
      suggested CRTR-D, which was confirmed by the detection of a known pathogenic
      mutation in the SLC6A8 gene (c.1631C>T; p.Pro544Leu).

PMID- 17553122
TI  - The new ILAE report on classification and evidence-based commentary on
      Panayiotopoulos syndrome and autonomic status epilepticus.

PMID- 17553123
TI  - Autonomic symptoms during childhood partial epileptic seizures.

PMID- 17553125
TI  - RLIP76 in AED drug resistance.

PMID- 17553127
TI  - Living with muscular dystrophy: health related quality of life consequences for
      children and adults.
AB  - BACKGROUND: Muscular dystrophies are chronic diseases manifesting with
      progressive muscle weakness leading to decreasing activities and participation.
      To understand the impact on daily life, it is important to determine patients'
      quality of life. OBJECTIVE: To investigate Health Related Quality of Life (HRQoL)
      of children and adults with muscular dystrophy (MD), and to study the influence
      of type and severity of MD on HRQoL in adult patients. METHODS: Age-related HRQoL
      questionnaires were administered to 40 children (8-17 years), and 67 adult
      patients with muscular dystrophies. RESULTS: Significant differences in HRQoL
      were found in children and adults with MD compared to healthy controls. Patients
      with Becker muscular dystrophy reported a better HRQoL on the several scales
      compared to patients with other MDs. Severity was associated with worse fine
      motor functioning and social functioning in adult patients. CONCLUSION: This is
      one of the first studies describing HRQoL of patients with MD using validated
      instruments in different age groups. The results indicate that having MD
      negatively influences the HRQoL on several domains.

PMID- 17553128
TI  - Dynamics of infection and competition between two strains of Trypanosoma brucei
      brucei in the tsetse fly observed using fluorescent markers.
AB  - BACKGROUND: Genetic exchange occurs between Trypanosoma brucei strains during the
      complex developmental cycle in the tsetse vector, probably within the salivary
      glands. Successful mating will depend on the dynamics of co-infection with
      multiple strains, particularly if intraspecific competition occurs. We have
      previously used T. brucei expressing green fluorescent protein to study parasite
      development in the vector, enabling even one trypanosome to be visualized. Here
      we have used two different trypanosome strains transfected with either green or
      red fluorescent proteins to study the dynamics of co-infection directly in the
      tsetse fly. RESULTS: The majority of infected flies had both trypanosome strains
      present in the midgut, but the relative proportion of red and green trypanosome
      strains varied considerably between flies and between different sections of the
      midgut in individual flies. Colonization of the paired salivary glands revealed
      greater variability than for midguts, as each gland could be infected with red
      and/or green trypanosome strains in variable proportions. Salivary glands with a
      mixed infection appeared to have a higher density of trypanosomes than glands
      containing a single strain. Comparison of the numbers of red and green
      trypanosomes in the proventriculus, salivary exudate and glands from individual
      flies showed no correlation between the composition of the trypanosome population
      of the proventriculus and foregut and that of the salivary glands. For each
      compartment examined (midgut, foregut, salivary glands), there was a
      significantly higher proportion of mixed infections than expected, assuming the
      null hypothesis that the development of each trypanosome strain is independent.
      CONCLUSION: Both the trypanosome strains used were fully capable of infecting
      tsetse, but the probabilities of infection with each strain were not independent,
      there being a significantly higher proportion of mixed infections than expected
      in each of three compartments examined: midgut, proventriculus and salivary
      glands. Hence there was no evidence of competition between trypanosome strains,
      but instead co-infection was frequent. Infection rates in co-infected flies were
      no different to those found routinely in flies infected with a single strain,
      ruling out the possibility that one strain enhanced infection with the other. We
      infer that each fly is either permissive or non-permissive of trypanosome
      infection with at least 3 sequential checkpoints imposed by the midgut,
      proventriculus and salivary glands. Salivary glands containing both trypanosome
      strains appeared to contain more trypanosomes than singly-infected glands,
      suggesting that lack of competition enhances the likelihood of genetic exchange.

PMID- 17553129
TI  - Prevalence of vancomycin-resistant enterococci colonization and its risk factors
      in chronic hemodialysis patients in Shiraz, Iran.
AB  - BACKGROUND: Vancomycin-resistant entrococci (VRE) are increasing in prevalence at
      many institutions, and are often reported in dialysis patients. The aim of this
      cross-sectional prevalence study was to determine the prevalence and risk factors
      of VRE colonization in chronic hemodialysis patients in two hemodialysis centers
      in Shiraz, Iran. METHODS: Rectal swabs were obtained from all consenting patients
      and were streaked on the surface of Cephalexin-aztreonam-arabinose agar (CAA) and
      incubated at 37 degrees C in air for 24 h. The vancomycin susceptibility of each
      isolate was confirmed by disk susceptibility testing. The MICs of vancomycin and
      teicoplanin were confirmed by the E test. To identify risk factors, a
      questionnaire was completed for all the studied patients and the data of VRE
      positive and negative groups were compared using Man-Withney U test for continues
      data and the Fisher exact test for categorical data. RESULTS: Of 146 patients
      investigated, 9 (6.2%) were positive for VRE. All VRE strains were genotypically
      distinguishable. Risk factors for a VRE-positive culture were "antimicrobial
      receipt within 2 months before culture" (P = 0.003) and "hospitalization during
      previous year" (P = 0.016). CONCLUSION: VRE colonization is an under-recognized
      problem among chronic dialysis patients in Iran. VRE colonization is associated
      with antibiotic consumption and hospitalization.

PMID- 17553130
TI  - Characterization of expressed sequence tags obtained by SSH during somatic
      embryogenesis in Cichorium intybus L.
AB  - BACKGROUND: Somatic embryogenesis (SE) is an asexual propagation pathway
      requiring a somatic-to-embryonic transition of differentiated somatic cells
      toward embryogenic cells capable of producing embryos in a process resembling
      zygotic embryogenesis. In chicory, genetic variability with respect to the
      formation of somatic embryos was detected between plants from a population of
      Cichorium intybus L. landrace Koospol. Though all plants from this population
      were self incompatible, we managed by repeated selfing to obtain a few seeds from
      one highly embryogenic (E) plant, K59. Among the plants grown from these seeds,
      one plant, C15, was found to be non-embryogenic (NE) under our SE-inducing
      conditions. Being closely related, we decided to exploit the difference in SE
      capacity between K59 and its descendant C15 to study gene expression during the
      early stages of SE in chicory. RESULTS: Cytological analysis indicated that in
      K59 leaf explants the first cell divisions leading to SE were observed at day 4
      of culture. In contrast, in C15 explants no cell divisions were observed and SE
      development seemed arrested before cell reactivation. Using mRNAs isolated from
      leaf explants from both genotypes after 4 days of culture under SE-inducing
      conditions, an E and a NE cDNA-library were generated by SSH. A total of 3,348
      ESTs from both libraries turned out to represent a maximum of 2,077 genes. In
      silico subtraction analysis sorted only 33 genes as differentially expressed in
      the E or NE genotype, indicating that SSH had resulted in an effective
      normalisation. Real-time RT-PCR was used to verify the expression levels of 48
      genes represented by ESTs from either library. The results showed preferential
      expression of genes related to protein synthesis and cell division in the E
      genotype, and related to defence in the NE genotype. CONCLUSION: In accordance
      with the cytological observations, mRNA levels in explants from K59 and C15
      collected at day 4 of SE culture reflected differential gene expression that
      presumably are related to processes accompanying early stages of direct SE. The E
      and NE library obtained thus represent important tools for subsequent detailed
      analysis of molecular mechanisms underlying this process in chicory, and its
      genetic control.

PMID- 17553131
TI  - Cytochrome P450arom, androgen and estrogen receptors in pig sperm.
AB  - BACKGROUND: Androgens and estrogens are crucial for mammalian sperm
      differentiation but their role in biology of mature male gamete is not still
      defined. The expression of proteins involved in the biosynthesis and action of
      these steroid hormones has been demonstrated in human spermatozoa, but very few
      data have been reported in mature sperm from non human species. The purpose of
      the current study was to investigate the expression of aromatase (P450arom),
      estrogen (ERalpha/ERbeta) and androgen (AR) receptors in ejaculated spermatozoa
      of pig. METHODS: The immunfluorescence experiments were carried out treating pig
      sperm with anti-P450arom, anti-ERalpha, anti-ERbeta and anti-AR as primary
      antibodies, while Texas-Red/FITC conjugated IgG were applied as secondary
      antibodies. Furthermore, Western blot analysis was performed on sperm lysates.
      RESULTS: Aromatase was immunolocalized in the sperm tail, ERalpha and AR were
      localised in the sperm midpiece, while ERbeta was confined in the acrosomal
      region of the male gamete. Immunoblots detected a ~52 kDa aromatase band, a ~110
      kDa AR band, a ~67 kDa ERalpha and two ERbeta bands, at ~50 kDa and ~59 kDa.
      CONCLUSION: This is the first report demonstrating that pig ejaculated
      spermatozoa express aromatase, estrogen and androgen receptors with a
      differential intra-cellular localization revealing a species-specific expression
      pattern. Therefore, pig sperm could be considered as a potential estrogen source
      while the different hormone cellular sites suggest distinct roles of androgens
      and estrogens in pig sperm physiology.

PMID- 17553132
TI  - Sensitivity and specificity of single IgA and IgG antibody concentrations for
      early diagnosis of pertussis in adults: an evaluation for outbreak management in
      public health practice.
AB  - BACKGROUND: An accurate, practical laboratory test is needed to confirm clinical
      diagnosis of pertussis in adults during the first 3 symptomatic weeks, when
      treatment is effective and transmission can be interrupted. METHODS: The
      sensitivity and specificity of single IgA and IgG levels were assessed in a
      cohort study of a pertussis epidemic in 99 adults in a closed community.
      Sensitivities were assessed in the sera of 46 laboratory confirmed clinical
      pertussis cases during the first 3 weeks. Specificities were calculated in sera
      of 35 asymptomatic controls without clinical symptoms or laboratory confirmed
      infections from the same community (internal controls). We compared these
      specificities with the specificities of single IgA and IgG levels in 4275
      external controls from a cross-section of the general Dutch population aged 21-79
      years who had not coughed for more than 2 weeks in the past year, and without
      pertussis diagnoses. The study was done in the Netherlands when whole-cell
      pertussis vaccine was used in the national vaccination programme. RESULTS: Levels
      of 24 U/ml for IgA and 27 U/ml for IgG gave sensitivities of 100% and 75%,
      respectively, in the first 2 weeks, 100% in the third week, and 97% after the
      fourth week. The levels were reached within 2 days after onset of increase, and
      remained above these levels for roughly 7.2 and 5.1 months, respectively.
      Specificity was 82% for IgA and 89% for IgG in the internal controls and 90% in
      the external controls, respectively. CONCLUSION: We suggest levels of 24 U/ml for
      IgA level and 27 U/ml (= 27 International Units (IU)/ml) for IgG as sensitive,
      specific, and practical for laboratory confirmation of clinical pertussis in
      adults in the first 3 weeks of outbreak management.

PMID- 17553134
TI  - Call for manuscripts: "Towards a scaling-up of training and education for health
      workers".

PMID- 17553133
TI  - Risk factors for breast cancer characterized by the estrogen receptor alpha A908G
      (K303R) mutation.
AB  - INTRODUCTION: Estrogen is important in the development of breast cancer, and its
      biological effects are mediated primarily through the two estrogen receptors
      alpha and beta. A point mutation in the estrogen receptor alpha gene, ESR1,
      referred to as A908G or K303R, was originally identified in breast hyperplasias
      and was reported to be hypersensitive to estrogen. We recently detected this
      mutation at a low frequency of 6% in invasive breast tumors of the Carolina
      Breast Cancer Study (CBCS). METHODS: In this report, we evaluated risk factors
      for invasive breast cancer classified according to the presence or absence of the
      ESR1 A908G mutation in the CBCS, a population-based case-control study of breast
      cancer among younger and older white and African-American women in North
      Carolina. Of the 653 breast tumors evaluated, 37 were ESR1 A908G mutation
      positive and 616 were mutation-negative. RESULTS: ESR1 A908G mutation-positive
      breast cancer was significantly associated with a first-degree family history of
      breast cancer (odds ratio [OR] = 2.69, 95% confidence interval [CI] = 1.15 to
      6.28), whereas mutation-negative breast cancer was not. Comparison of the two
      case subgroups supported this finding (OR = 2.65, 95% CI = 1.15 to 6.09). There
      was also the suggestion that longer duration of oral contraceptive (OC) use (OR =
      3.73, 95% CI = 1.16 to 12.03; Ptrend = 0.02 for use of more than 10 years) and
      recent use of OCs (OR = 3.63, 95% CI = 0.80 to 16.45; Ptrend = 0.10 for use
      within 10 years) were associated with ESR1 A908G mutation-positive breast cancer;
      however, ORs for comparison of the two case subgroups were not statistically
      significant. Hormone replacement therapy use was inversely correlated with
      mutation-negative breast cancer, but the effect on mutation-positive cancer was
      unclear due to the small number of postmenopausal cases whose tumors carried the
      mutation. Mutation-negative breast cancer was associated with several
      reproductive factors, including younger age at menarche (OR = 1.46, 95% CI = 1.09
      to 1.94) and greater total estimated years of ovarian function (OR = 1.82, 95% CI
      = 1.21 to 2.74). CONCLUSION: These preliminary results suggest that OCs may
      interact with the ESR1 A908G mutant receptor to drive the development of some
      breast tumors.

PMID- 17553135
TI  - Social richness, socio-technical tension and the virtual commissioning of NHS
      research.
AB  - BACKGROUND: This paper draws on a recent study that evaluated the process of
      commissioning NHS funded research using virtual committees. Building on an
      earlier paper that reported our evaluation, here we focus on the effects of
      asynchronous computer mediated communication (CMC) when used to support group
      work. METHODS: To do this the discussion focuses on how CMC affected three key
      group factors, building relationships, group cohesion and group commitment. The
      notion of socio-technical tension is elaborated and the paper explores how social
      richness can act to counter the socially impoverishing and time extending effects
      of asynchronous CMC. RESULTS: We argue that social richness in this context
      results from the presence of five principal influences. These are: a dynamic
      range of participant aspirations and personal agendas; participant commitment to
      and identification with the work and ideals of the group; a rich diversity of
      social, professional and work-related backgrounds; a website designed to enhance
      participation and interaction and the mediating effects of an effective
      chairperson. CONCLUSION: If virtual work groups are to be used by the NHS in the
      future, then there is a need for more research into the role of social context
      and its relationship to the effectiveness of newly formed virtual groups. Equally
      as important are studies that examine the effects of socio-technical interaction
      on groups undertaking tasks in the real world of work.

PMID- 17553136
TI  - HIV/AIDS in Russia: determinants of regional prevalence.
AB  - BACKGROUND: The motivation for this paper is to inform the selection of future
      policy directions for tackling HIV/AIDS in Russia. The Russian Federation has
      more people living with HIV/AIDS than any other country in Europe, and nearly 70%
      of the known infections in Eastern Europe and Central Asia. The epidemic is
      particularly young, with 80% of those infected aged less than thirty, and no
      Russian region has escaped the detection of infections. However, measures to
      address the epidemic in Russia have been hampered by late recognition of the
      scale of the problem, poor data on HIV prevalence, potentially counterproductive
      narcotics legislation, and competing health priorities. An additional
      complication has been the relative lack of research into the spatial
      heterogeneity of the Russian HIV/AIDS epidemic, investigating the variety of
      prevalence rates in the constituent regions and questioning assumptions about the
      links between the epidemic and the circumstances of post-Soviet transformation.
      In the light of these recent developments, this paper presents research into the
      determinants of regional HIV prevalence levels in Russia. RESULTS: Statistical
      empirical research on HIV and other infectious diseases has identified a variety
      of factors that influence the spread and development of these diseases. In our
      empirical analysis of determinants of HIV prevalence in Russia at the regional
      level, we identify factors that are statistically related to the level of HIV
      prevalence in Russian regions, and obtain some indication of the relative
      importance of these factors. We estimate an empirical model that includes factors
      which describe economic and socio-cultural characteristics. CONCLUSION: Our
      analysis statistically identifies four main factors that influence HIV prevalence
      in Russian regions. Given the different nature of the factors that we identify to
      be of importance, we conclude that successful HIV intervention policies will need
      to be multidisciplinary in nature. Finally, we stress that further research is
      needed to obtain a better understanding of the statistical relations that we have
      identified; our empirical findings can serve as an important guide in these
      future research efforts, as they indicate which processes play an important role
      in regional HIV/AIDS prevalence rates in contemporary Russia.

PMID- 17553137
TI  - Imported Crimean-Congo hemorrhagic fever cases in Istanbul.
AB  - We described a series of imported cases of Crimean-Congo Hemorrhagic Fever (CCHF)
      in Istanbul and investigated the genetic diversity of the virus. All the
      suspected cases of CCHF, who were applied to the health centers in Istanbul, were
      screened for CCHF virus (CCHFv) infection by using semi-nested Polymerase Chain
      Reaction (PCR) following RT-PCR. Simultaneous blood samples were also sent to the
      national reference laboratory in Ankara for serologic investigation. In 10 out of
      91 patients, CCHFv was detected by PCR, and among 9 out of 10, anti-CCHFv IgM
      antibodies were also positive. Clinical features were characterized by fever,
      myalgia, and hemorrhage. The levels of liver enzymes, creatinine phosphokinase,
      and lactate dehydrogenase were elevated, and bleeding markers were prolonged. All
      the cases were treated with ribavirin. There was no fatal case. All the strains
      clustered within the same group as other Europe/Turkey isolates.

PMID- 17553138
TI  - First comprehensive contribution to medical ethnobotany of Western Pyrenees.
AB  - BACKGROUND: An ethnobotanical and medical study was carried out in the Navarre
      Pyrenees, an area known both for its high biological diversity and its cultural
      significance. As well as the compilation of an ethnopharmacological catalogue, a
      quantitative ethnobotanical comparison has been carried out in relation to the
      outcomes from other studies about the Pyrenees. A review of all drugs used in the
      area has also been carried out, through a study of the monographs published by
      the institutions and organizations responsible for the safety and efficacy of
      medicinal plants (WHO, ESCOP, and the E Commission of the German Department of
      Health) in order to ascertain the extent to which the Navarre Pyrenees
      ethnopharmacology has been officially evaluated. METHODS: Fieldwork was carried
      out over two years, from November 2004 to December 2006. During that time we
      interviewed 88 local people in 40 villages. Information was collected using semi
      structured ethnobotanical interviews and the data was analyzed using quantitative
      indexes: Ethnobotonicity Index, Shannon-Wiener's Diversity, Equitability and The
      Informant Consensus Factor. The official review has been performed using the
      official monographs published by the WHO, ESCOP and the E Commission of the
      German Department of Health. RESULTS: The ethnobotanical and medical catalogue of
      the Navarre Pyrenees Area comprises 92 species, of which 39 have been mentioned
      by at least three interviewees. The quantitative ethnobotany results show lower
      values than those found in other studies about the Pyrenees; and 57.6% of the
      Pyrenees medical ethnobotany described does not figure in documents published by
      the above mentioned institutions. CONCLUSION: The results show a reduction in the
      ethnobotanical and medical knowledge in the area of study, when compared to other
      studies carried out in the Pyrenees. Nevertheless, the use of several species
      that may be regarded as possible sources for pharmacological studies is reported
      here such as the bark of Sambucus nigra, the roots of Fragaria vesca, or the
      leaves of Scrophularia nodosa. These species are not currently approved by the
      WHO, ESCOP and the E Commission of the German Department of Health, institutions
      that, apart from encouraging the greater use of plants for medicinal purposes,
      may help in the design of development plans for these rural areas by validating
      their traditional medicine.

PMID- 17553139
TI  - The PTPN22 1858C/T polymorphism is associated with anti-cyclic citrullinated
      peptide antibody-positive early rheumatoid arthritis in northern Sweden.
AB  - The PTPN22 1858C/T polymorphism has been associated with several autoimmune
      diseases including rheumatoid arthritis (RA). We have shown that carriage of the
      T variant (CT or TT) of PTPN22 in combination with anti-cyclic citrullinated
      peptide (anti-CCP) antibodies highly increases the odds ratio for developing RA.
      In the present study we analysed the association between the PTPN22 1858C/T
      polymorphism and early RA in patients from northern Sweden, related the
      polymorphism to autoantibodies and the HLA-DR shared epitope, and analysed their
      association with markers for disease activity and progression. The inception
      cohort includes individuals who also donated samples before disease onset. A case
      control study was performed in patients (n = 505; 342 females and 163 males) with
      early RA (mean duration of symptoms = 6.3 months) and in population-based matched
      controls (n = 970) from northern Sweden. Genotyping of the PTPN22 1858C/T
      polymorphism was performed using a TaqMan instrument. HLA-shared epitope alleles
      were identified using PCR sequence-specific primers. Anti-CCP2 antibodies were
      determined using enzyme-linked immunoassays. Disease activity (that is, the
      number of swollen and tender joints, the global visual analogue scale, and the
      erythrocyte sedimentation rate) was followed on a regular basis (that is, at
      baseline and after 6, 12, 18 and 24 months). Both the 1858T allele and the
      carriage of T were associated with RA (chi2 = 23.84, P = 0.000001, odds ratio =
      1.69, 95% confidence interval = 1.36-2.11; and chi2 = 22.68, P = 0.000002, odds
      ratio = 1.79, 95% confidence interval = 1.40-2.29, respectively). Association of
      the 1858T variant with RA was confined to seropositive disease. Carriage of 1858T
      and the presence of anti-CCP antibodies was independently associated with disease
      onset at an earlier age (P < 0.05 and P < 0.01, respectively), while the
      combination of both resulted in an even earlier age at onset. Smoking was
      identified as a risk factor independent of the 1858T variant and anti-CCP
      antibodies.

PMID- 17553140
TI  - Injection drug use and patterns of highly active antiretroviral therapy use: an
      analysis of ALIVE, WIHS, and MACS cohorts.
AB  - BACKGROUND: Sustained use of antiretroviral therapy has been consistently shown
      to be one of the primary predictors of long-term effectiveness. Switching and
      discontinuation reflect patient and provider decisions that may limit future
      treatment options. In this study, we utilize data reported at semi-annual study
      visits from three prospective cohort studies, the AIDS Link to IntraVenous
      Exposure (ALIVE), the Women's Interagency HIV Study (WIHS), and the Multicenter
      AIDS Cohort Study (MACS), to investigate determinants of HAART modification with
      a particular focus on reported injection drug use (IDU). METHODS: Longitudinal
      data collected between 1996 and 2004 contributed from 2,266 participants (37%
      with a reported history of IDU) who reported initiating their first HAART regimen
      during follow-up were utilized. Separate proportional-hazards models were used to
      identify factors measured prior to HAART-initiation associated with the time to
      first HAART discontinuation and first switch of components of HAART among
      continuous HAART users. RESULTS: The use of PI- vs. NNRTI-based regimens among
      HAART users with and without any history of IDU was similar over follow-up. The
      median time to a first report of discontinuation of HAART was 1.1 years for
      individuals with a history of IDU but 2.5 years for those without a history of
      IDU and multivariate analyses confirmed overall that individuals with a history
      of IDU were at greater risk for HAART discontinuation (adj RH = 1.24, 95% CI:
      1.03-1.48). However, when restricting to data contributed after 1999, there was
      no longer any significant increased risk (adj RH = 1.05, 95% CI: 0.81-1.36).
      After adjusting for pre-HAART health status and prior ARV exposure, individuals
      who were ethnic/racial minorities, reported an annual income < $10,000/year, and
      were not employed were at significantly greater risk for HAART discontinuation.
      The median time to a first change in HAART regimen was approximately 1.5 years
      after first HAART report and was not elevated among those with a history of IDU
      (adj RH = 1.09, 95% CI: 0.89-1.34). CONCLUSION: Our analyses demonstrate that
      injection drug use by itself does not appear to be an independent risk factor for
      HAART switching or discontinuation in more recent years. However, as continued
      HAART use is of paramount importance for long-term control of HIV infection,
      efforts to improve maintenance to therapy among disadvantaged and minority
      populations remain greatly needed.

PMID- 17553141
TI  - Vertebral hyperostosis, ankylosed vertebral fracture and atlantoaxial rotatory
      subluxation in an elderly patient with a history of infantile idiopathic
      scoliosis; a case report.
AB  - This is a case report of a 48-year-old-woman with scoliosis since early
      childhood. Recent radiographic spinal assessment revealed the presence of
      distinctive spinal abnormalities. To the best of our knowledge this is the first
      clinical report describing a constellation of unusual changes in an elderly woman
      with a history of infantile idiopathic scoliosis.

PMID- 17553142
TI  - Atypical presentation of renal cell carcinoma: a case report.
AB  - A case of Renal Cell Carcinoma (RCC) presenting to the Emergency Department with
      pyrexia and rigors is discussed.

PMID- 17553143
TI  - Neuronal mechanism for neuropathic pain.
AB  - Among different forms of persistent pain, neuropathic pain presents as a most
      difficult task for basic researchers and clinicians. Despite recent rapid
      development of neuroscience and modern techniques related to drug discovery,
      effective drugs based on clear basic mechanisms are still lacking. Here, I will
      review the basic neuronal mechanisms that maybe involved in neuropathic pain. I
      will present the problem of neuropathic pain as a rather difficult task for
      neuroscientists, and we may have to wait for a long time before we fully
      understand how brain encode, store, and retrieve painful information after the
      injury. I propose that neuropathic pain as a major brain disease, rather being a
      clinic problem due to peripheral injury.

PMID- 17553145
TI  - Local recurrence and distant metastases 18 years after resection of the greater
      omentum hemangiopericytoma.
AB  - BACKGROUND: Hemangiopericytoma occurs with increasing frequency in 5th decade of
      life and has prediction for retroperitoneum and extremities. A case of a local
      recurrence and metastases of hemangiopericytoma is described. CASE PRESENTATION:
      Recurrence of hemangiopericytoma in the greater omentum and the jejunal mesentery
      as well as metastases in the retroperitoneal space were diagnosed in a 61-year
      old patient who had a hemangiopericytoma of the greater omentum excised 18 years
      before. CONCLUSION: Because of the rarity of this disease and its typical
      clinical course associated with late recurrence and metastases, the authors
      decided to present this case emphasizing the necessity of systematic oncological
      follow-up after the end of treatment.

PMID- 17553144
TI  - Transfusion-transmitted infections.
AB  - Although the risk of transfusion-transmitted infections today is lower than ever,
      the supply of safe blood products remains subject to contamination with known and
      yet to be identified human pathogens. Only continuous improvement and
      implementation of donor selection, sensitive screening tests and effective
      inactivation procedures can ensure the elimination, or at least reduction, of the
      risk of acquiring transfusion transmitted infections. In addition, ongoing
      education and up-to-date information regarding infectious agents that are
      potentially transmitted via blood components is necessary to promote the
      reporting of adverse events, an important component of transfusion transmitted
      disease surveillance. Thus, the collaboration of all parties involved in
      transfusion medicine, including national haemovigilance systems, is crucial for
      protecting a secure blood product supply from known and emerging blood-borne
      pathogens.

PMID- 17553146
TI  - The red fluorescent protein eqFP611: application in subcellular localization
      studies in higher plants.
AB  - BACKGROUND: Intrinsically fluorescent proteins have revolutionized studies in
      molecular cell biology. The parallel application of these proteins in dual- or
      multilabeling experiments such as subcellular localization studies requires non
      overlapping emission spectra for unambiguous detection of each label. In the red
      spectral range, almost exclusively DsRed and derivatives thereof are used today.
      To test the suitability of the red fluorescent protein eqFP611 as an alternative
      in higher plants, the behavior of this protein was analyzed in terms of
      expression, subcellular targeting and compatibility with GFP in tobacco. RESULTS:
      When expressed transiently in tobacco protoplasts, eqFP611 accumulated over night
      to levels easily detectable by fluorescence microscopy. The native protein was
      found in the nucleus and in the cytosol and no detrimental effects on cell
      viability were observed. When fused to N-terminal mitochondrial and peroxisomal
      targeting sequences, the red fluorescence was located exclusively in the
      corresponding organelles in transfected protoplasts. Upon co-expression with GFP
      in the same cells, fluorescence of both eqFP611 and GFP could be easily
      distinguished, demonstrating the potential of eqFP611 in dual-labeling
      experiments with GFP. A series of plasmids was constructed for expression of
      eqFP611 in plants and for simultaneous expression of this fluorescent protein
      together with GFP. Transgenic tobacco plants constitutively expressing
      mitochondrially targeted eqFP611 were generated. The red fluorescence was stably
      transmitted to the following generations, making these plants a convenient source
      for protoplasts containing an internal marker for mitochondria. CONCLUSION: In
      plants, eqFP611 is a suitable fluorescent reporter protein. The unmodified
      protein can be expressed to levels easily detectable by epifluorescence
      microscopy without adverse affect on the viability of plant cells. Its
      subcellular localization can be manipulated by N-terminal signal sequences.
      eqFP611 and GFP are fully compatible in dual-labeling experiments.

PMID- 17553147
TI  - Red blood cell transfusions and the risk of acute respiratory distress syndrome
      among the critically ill: a cohort study.
AB  - INTRODUCTION: Recent data indicate that transfusion of packed red blood cells
      (pRBCs) may increase the risk for the development of acute respiratory distress
      syndrome (ARDS) in critically ill patients. Uncertainty remains regarding the
      strength of this relationship. METHODS: To quantify the association between
      transfusions and intensive care unit (ICU)-onset ARDS, we performed a cohort
      study within Crit, a multicenter, prospective, observational study of transfusion
      practice in the ICU which enrolled 4,892 critically ill patients in 284 ICUs in
      the United States. Diagnostic criteria for ARDS were prospectively defined, and
      we focused on subjects without ARDS at admission. The development of ARDS in the
      ICU served as the primary endpoint. RESULTS: Among the 4,730 patients without
      ARDS at admission, 246 (5.2%) developed ARDS in the ICU. At baseline, ARDS cases
      were younger, more likely to be in a surgical ICU, and more likely to be admitted
      with pneumonia or sepsis than controls without ARDS. Cases also were more likely
      to have a serum creatinine of greater than 2.0 mg/dl (23% versus 18%) and a serum
      albumin of less than or equal to 2.3 g/dl (54% versus 30%) and were more severely
      ill upon ICU admission as measured by either the APACHE II (Acute Physiology and
      Chronic Health Evaluation II) or SOFA (Sequential Organ Failure Assessment) score
      (p < 0.05 for all). Sixty-seven percent and 42% of cases and controls,
      respectively, had exposure to pRBC transfusions (p < 0.05), and the unadjusted
      odds ratio (OR) of developing ARDS in transfused patients was 2.74 (95%
      confidence interval [CI], 2.09 to 3.59; p < 0.0001) compared to those never
      transfused. After age, baseline severity of illness, admitting diagnosis, and
      process-of-care factors were adjusted for, the independent relationship between
      pRBC transfusions and ICU-onset ARDS remained significant (adjusted OR, 2.80; 95%
      CI, 1.90 to 4.12; p < 0.0001). CONCLUSION: Development of ARDS after ICU
      admission is common, occurring in approximately 5% of critically ill patients.
      Transfusion of pRBCs is independently associated with the development of ARDS in
      the ICU.

PMID- 17553149
TI  - Detection of virus mRNA within infected host cells using an isothermal nucleic
      acid amplification assay: marine cyanophage gene expression within Synechococcus
      sp.
AB  - BACKGROUND: Signal-Mediated Amplification of RNA Technology (SMART) is an
      isothermal nucleic acid amplification technology, developed for the detection of
      specific target sequences, either RNA (for expression) or DNA. Cyanophages are
      viruses that infect cyanobacteria. Marine cyanophages are ubiquitous in the
      surface layers of the ocean where they infect members of the globally important
      genus Synechococcus. RESULTS: Here we report that the SMART assay allowed us to
      differentiate between infected and non-infected host cultures. Expression of the
      cyanophage strain S-PM2 portal vertex gene (g20) was detected from infected host
      Synechococcus sp. WH7803 cells. Using the SMART assay, we demonstrated that g20
      mRNA peaked 240-360 minutes post-infection, allowing us to characterise this as a
      mid to late transcript. g20 DNA was also detected, peaking 10 hours post
      infection, coinciding with the onset of host lysis. CONCLUSION: The SMART assay
      is based on isothermal nucleic acid amplification, allowing the detection of
      specific sequences of DNA or RNA. It was shown to be suitable for differentiating
      between virus-infected and non-infected host cultures and for the detection of
      virus gene expression: the first reported use of this technology for such
      applications.

PMID- 17553148
TI  - Uptake and metabolism of ciclesonide and retention of desisobutyryl-ciclesonide
      for up to 24 hours in rabbit nasal mucosa.
AB  - BACKGROUND: The nasal tissue uptake and metabolism of ciclesonide, a new
      generation corticosteroid under investigation for treatment of allergic rhinitis,
      to its active metabolite, desisobutyryl-ciclesonide (des-CIC), was evaluated when
      administered to rabbits in a hypotonic versus an isotonic ciclesonide suspension.
      Nasal mucosa extracts from normal Japanese white rabbits were evaluated by high
      performance liquid chromatography with tandem mass spectrometry detection after a
      single 143-mug dose of ciclesonide. Retention and formation of fatty acid
      conjugates of des-CIC were also measured in nasal mucosa extracts
      postadministration of a hypotonic ciclesonide suspension (143-mug single dose).
      RESULTS: Versus an isotonic suspension, the hypotonic suspension achieved higher
      concentrations of des-CIC (5.6-fold, 11.4-fold, and 13.4-fold; p < 0.05 for all)
      and ciclesonide (25.3-fold, 34.2-fold [p = not significant], and 16-fold [p <
      0.05]) at 30, 120, and 240 min postadministration. Additionally, when
      administered via a hypotonic suspension, des-CIC was retained up to 24 h
      postadministration (45.46 pmol/g tissue). Highest concentration of major fatty
      acid ester conjugate, des-CIC-oleate, was detected in nasal mucosa at 8 h
      postadministration. CONCLUSION: These data suggest that a hypotonic ciclesonide
      suspension provides higher intracellular concentrations of des-CIC up to 24 h,
      thereby providing a rationale for investigation of ciclesonide as a convenient
      once-daily nasal spray for treatment of allergic rhinitis.

PMID- 17553150
TI  - Simple models of genomic variation in human SNP density.
AB  - BACKGROUND: Descriptive hierarchical Poisson models and population-genetic
      coalescent mixture models are used to describe the observed variation in single
      nucleotide polymorphism (SNP) density from samples of size two across the human
      genome. RESULTS: Using empirical estimates of recombination rate across the human
      genome and the observed SNP density distribution, we produce a maximum likelihood
      estimate of the genomic heterogeneity in the scaled mutation rate theta. Such
      models produce significantly better fits to the observed SNP density distribution
      than those that ignore the empirically observed recombinational heterogeneities.
      CONCLUSION: Accounting for mutational and recombinational heterogeneities can
      allow for empirically sound null distributions in genome scans for "outliers",
      when the alternative hypotheses include fundamentally historical and unobserved
      phenomena.

PMID- 17553151
TI  - Ertapenem susceptibility of extended spectrum beta-lactamase-producing organisms.
AB  - BACKGROUND: Infections caused by multiply drug resistant organisms such as
      extended spectrum beta-lactamase (ESBL)-producing Escherichia coli and Klebsiella
      pneumoniae are increasing. Carbapenems (imipenem and meropenem) are the
      antibiotics commonly used to treat these agents. There is limited clinical data
      regarding the efficacy of the newest carbapenem, ertapenem, against these
      organisms. Ertapenem susceptibility of ESBL-producing E. coli and K. pneumoniae
      clinical isolates were evaluated and compared to imipenem to determine if
      imipenem susceptibility could be used as a surrogate for ertapenem
      susceptibility. METHODS: 100 ESBL isolates (n = 34 E. coli and n = 66 K.
      pneumoniae) collected from 2005-2006 clinical specimens at WRAMC were identified
      and tested for susceptibility by Vitek Legacy [bioMerieux, Durham, NC]. Ertapenem
      susceptibility was performed via epsilometer test (E-test) [AB Biodisk, Solna,
      Sweden]. RESULTS: 100% of ESBL isolates tested were susceptible to ertapenem.
      100% of the same isolates were also susceptible to imipenem. CONCLUSION: These
      results, based on 100% susceptibility, suggest that ertapenem may be an
      alternative to other carbapenems for the treatment of infections caused by ESBL
      producing E. coli and K. pneumoniae. Clinical outcomes studies are needed to
      determine if ertapenem is effective for the treatment of infection caused by
      these organisms. However, due to lack of resistant isolates, we are unable to
      conclude whether imipenem susceptibility accurately predicts ertapenem
      susceptibility.

PMID- 17553152
TI  - Standardization of surface electromyography utilized to evaluate patients with
      dysphagia.
AB  - BACKGROUND: Patients suspected of having swallowing disorders, could highly
      benefit from simple diagnostic screening before being referred to specialist
      evaluations. We introduce surface electromyography (sEMG) to carry out rapid
      assessment of such patients and propose suggestions for standardizing sEMGs in
      order to identify abnormal deglutition. METHODS: Specifics steps for establishing
      standards for applying the technique for screening purposes (e.g., evaluation of
      specific muscles), the requirements for diagnostic sEMG equipment, the sEMG
      technique itself, and defining the tests suitable for assessing deglutition
      (e.g., saliva, normal, and excessive swallows and uninterrupted drinking of
      water) are presented in detail. A previously described normative database for
      single swallowing and drinking and standard approach to analysis was compared to
      data on the duration and electric activity of muscles involved in deglutition and
      with sEMG recordings in order to estimate stages of a swallow. CONCLUSION: SEMG
      of swallowing is a simple and reliable method for screening and preliminary
      differentiation among dysphagia and odynophagia of various origins. This
      noninvasive radiation-free examination has a low level of discomfort, and is
      simple, timesaving and inexpensive to perform. With standardization of the
      technique and an established normative database, sEMG can serve as a reliable
      screening method for optimal patient management.

PMID- 17553153
TI  - Effective media communication of disasters: pressing problems and
      recommendations.
AB  - BACKGROUND: Public health officials and journalists play a crucial role in
      disseminating information regarding natural disasters, terrorism and other human
      initiated disasters. However, research suggests that journalists are unprepared
      to cover terrorism and many types of natural disasters, in part because of lack
      sufficient expertise in science and medicine and training. The objective of this
      research was to identify solutions to problems facing journalists and public
      health public information officer (PIOs) of communicating with the public during
      natural and human-initiated disasters. METHODS: To assist in identifying the most
      pressing problems regarding media response to health-related risks such as
      terrorism and large-scale natural disasters, 26 expert advisors were convened,
      including leaders representing journalists and public information officers, state
      health officials, experts in terrorism and emergency preparedness, and experts in
      health, risk, and science communication. The advisory group participated in pre
      arranged interviews and were asked to identify and review bioterrorism
      educational resources provided to journalist. All advisory group members were
      then invited to attend a day long meeting January 29, 2004 to review the findings
      and reach consensus. RESULTS: The most pressing problems were found to be a lack
      of coordination between PIO's and journalists, lack of resources for
      appropriately evaluating information and disseminating it efficiently, and a
      difference in perception of PIO's and journalist towards each others role during
      emergency situations. The advisory board developed a list of 15 recommendations
      that may enhance communication plans between PIO's, journalist and the public.
      The solutions were meant to be feasible in terms of costs and practical in terms
      of the professional and organizational realities in which journalists and PIO's
      work. CONCLUSION: It is clear that PIO's and journalists play crucial roles in
      shaping public response to terrorism and other disasters. The findings from this
      formative research suggest that perspectives and organizational processes often
      limit effective communication between these groups; though practical solutions
      such as participation of journalists in drills, scenario exercises, sharing of
      informational resources, and raising awareness at professional trade meetings may
      enhance the timely dissemination of accurate and appropriate information.

PMID- 17553154
TI  - Recurrent burner syndrome due to presumed cervical spine osteoblastoma in a
      collision sport athlete - a case report.
AB  - We present a case of a 35-year-old active rugby player presenting with a history
      of recurrent burner syndrome thought secondary to an osteoblastoma involving the
      posterior arch of the atlas. Radiographically, the lesion had features typical
      for a large osteoid osteoma or osteoblastoma, including osseous expansion,
      peripheral sclerosis and bony hypertrophy, internal lucency, and even suggestion
      of a central nidus. The patient subsequently underwent an en bloc resection of
      the posterior atlas via a standard posterior approach. The surgery revealed very
      good clinical results. In this report, we will discuss in detail, the
      presentation, treatment, and return to play recommendations involving this
      patient.

PMID- 17553155
TI  - Global gene expression profiling in human lung cells exposed to cobalt.
AB  - BACKGROUND: It has been estimated that more than 1 million workers in the United
      States are exposed to cobalt. Occupational exposure to 59 Co occurs mainly via
      inhalation and leads to various lung diseases. Cobalt is classified by the IARC
      as a possible human carcinogen (group 2B). Although there is evidence for in vivo
      and in vitro toxicity, the mechanisms of cobalt-induced lung toxicity are not
      fully known. The purpose of this work was to identify potential signatures of
      acute cobalt exposure using a toxicogenomic approach. Data analysis focused on
      some cellular processes and protein targets that are thought to be relevant for
      carcinogenesis, transport and biomarker research. RESULTS: A time course
      transcriptome analysis was performed on A549 human pulmonary cells, leading to
      the identification of 85 genes which are repressed or induced in response to
      soluble 59 Co. A group of 29 of these genes, representing the main biological
      functions, was assessed by quantitative RT-PCR. The expression profiles of six of
      them were then tested by quantitative RT-PCR in a time-dependent manner and three
      modulations were confirmed by Western blotting. The 85 modulated genes include
      potential cobalt carriers (FBXL2, ZNT1, SLC12A5), tumor suppressors or
      transcription factors (MAZ, DLG1, MYC, AXL) and genes linked to the stress
      response (UBC, HSPCB, BNIP3L). We also identified nine genes coding for secreted
      proteins as candidates for biomarker research. Of those, TIMP2 was found to be
      down-regulated and this modulation was confirmed, in a dose-dependent manner, at
      protein level in the supernatant of exposed cells. CONCLUSION: Most of these
      genes have never been described as related to cobalt stress and provide original
      hypotheses for further study of the effects of this metal ion on human lung
      epithelial cells. A putative biomarker of cobalt toxicity was identified.

PMID- 17553156
TI  - A functional map of NFkappaB signaling identifies novel modulators and multiple
      system controls.
AB  - BACKGROUND: The network of signaling pathways that leads to activation of the
      NFkappaB transcription factors is a branched structure with different inputs and
      cross-coupling with other signaling pathways. How these signals are integrated to
      produce specific, yet diverse responses is not clearly understood. To identify
      the components and structural features of the NFkappaB network, a series of cell
      based, genomic screens was performed using a library of approximately 14,500 full
      length genes. RESULTS: A total of 154 positive and 88 negative modulators of
      NFkappaB signaling were identified. Using a series of dominant-negative
      constructs and functional assays, these modulators were mapped to the known
      NFkappaB signaling cascade. Most of the positive modulators acted upstream of the
      IkappaB kinase complex, supporting previous observations that the IkappaB kinases
      represent the primary point of convergence in the network. A number of negative
      modulators were localized downstream of the IkappaB kinase beta (IKBKB) subunit,
      suggesting that they form an additional layer of negative control within the
      system. The expression of the modulators at the RNA level was distributed
      disproportionately across tissues, providing flexibility in network structure,
      and the number of positive and negative modulators present in a given tissue was
      highly correlated, suggesting that positive and negative regulation is balanced
      at the tissue level. CONCLUSION: The relative locations of the modulators are
      consistent with an hourglass structure for the NFkappaB network that is
      characteristic of robust systems. The tissue distribution of the modulators and
      downstream location of the negative modulators serve as layers of control within
      the system that allow differential responses to different stimuli.

PMID- 17553157
TI  - Improving model predictions for RNA interference activities that use support
      vector machine regression by combining and filtering features.
AB  - BACKGROUND: RNA interference (RNAi) is a naturally occurring phenomenon that
      results in the suppression of a target RNA sequence utilizing a variety of
      possible methods and pathways. To dissect the factors that result in effective
      siRNA sequences a regression kernel Support Vector Machine (SVM) approach was
      used to quantitatively model RNA interference activities. RESULTS: Eight overall
      feature mapping methods were compared in their abilities to build SVM regression
      models that predict published siRNA activities. The primary factors in predictive
      SVM models are position specific nucleotide compositions. The secondary factors
      are position independent sequence motifs (N-grams) and guide strand to passenger
      strand sequence thermodynamics. Finally, the factors that are least contributory
      but are still predictive of efficacy are measures of intramolecular guide strand
      secondary structure and target strand secondary structure. Of these, the site of
      the 5' most base of the guide strand is the most informative. CONCLUSION: The
      capacity of specific feature mapping methods and their ability to build
      predictive models of RNAi activity suggests a relative biological importance of
      these features. Some feature mapping methods are more informative in building
      predictive models and overall t-test filtering provides a method to remove some
      noisy features or make comparisons among datasets. Together, these features can
      yield predictive SVM regression models with increased predictive accuracy between
      predicted and observed activities both within datasets by cross validation, and
      between independently collected RNAi activity datasets. Feature filtering to
      remove features should be approached carefully in that it is possible to reduce
      feature set size without substantially reducing predictive models, but the
      features retained in the candidate models become increasingly distinct. Software
      to perform feature prediction and SVM training and testing on nucleic acid
      sequences can be found at the following site:
      ftp://scitoolsftp.idtdna.com/SEQ2SVM/.

PMID- 17553159
TI  - Introduction to the special issue from the proceedings of the 2006 International
      Workshop on Virtual Reality in Rehabilitation.
AB  - New technologies are rapidly having a great impact on the development of novel
      rehabilitation interventions. One of the more popular of these technological
      advances is virtual reality. The wide range of applications of this technology,
      from immersive environments to tele-rehabilitation equipment and care, lends
      versatility to its use as a rehabilitation intervention. But increasing access to
      this technology requires that we further our understanding about its impact on a
      performer. The International Workshop on Virtual Reality in Rehabilitation
      (IWVR), now known as Virtual Rehabilitation 2007, is a conference that emerged
      from the need to discover how virtual reality could be applied to rehabilitation
      practice. Individuals from multiple disciplines concerned with the development,
      transmission, and evaluation of virtual reality as a technology applied to
      rehabilitation attend this meeting to share their work. In this special issue of
      the Journal of NeuroEngineering and Rehabilitation we are sharing some of the
      papers presented at the 2006 meeting of IWVR with the objective of offering a
      description of the state of the art in this research field. A perusal of these
      papers will provide a good cross-section of the emerging work in this area as
      well as inform the reader about new findings relevant to research and practice in
      rehabilitation.

PMID- 17553158
TI  - Clearance of an immunosuppressive virus from the CNS coincides with immune
      reanimation and diversification.
AB  - Once a virus infection establishes persistence in the central nervous system
      (CNS), it is especially difficult to eliminate from this specialized compartment.
      Therefore, it is of the utmost importance to fully understand scenarios during
      which a persisting virus is ultimately purged from the CNS by the adaptive immune
      system. Such a scenario can be found following infection of adult mice with an
      immunosuppressive variant of lymphocytic choriomeningitis virus (LCMV) referred
      to as clone 13. In this study we demonstrate that following intravenous
      inoculation, clone 13 rapidly infected peripheral tissues within one week, but
      more slowly innundated the entire brain parenchyma over the course of a month.
      During the establishment of persistence, we observed that genetically tagged LCMV
      specific cytotoxic T lymphocytes (CTL) progressively lost function; however, the
      severity of this loss in the CNS was never as substantial as that observed in the
      periphery. One of the most impressive features of this model system is that the
      peripheral T cell response eventually regains functionality at ~60-80 days post
      infection, and this was associated with a rapid decline in virus from the
      periphery. Coincident with this "reanimation phase" was a massive influx of CD4 T
      and B cells into the CNS and a dramatic reduction in viral distribution. In fact,
      olfactory bulb neurons served as the last refuge for the persisting virus, which
      was ultimately purged from the CNS within 200 days post-infection. These data
      indicate that a functionally revived immune response can prevail over a virus
      that establishes widespread presence both in the periphery and brain parenchyma,
      and that therapeutic enhancement of an existing response could serve as an
      effective means to thwart long term CNS persistence.

PMID- 17553160
TI  - Homologous high-throughput expression and purification of highly conserved E coli
      proteins.
AB  - BACKGROUND: Genetic factors and a dysregulated immune response towards commensal
      bacteria contribute to the pathogenesis of Inflammatory Bowel Disease (IBD).
      Animal models demonstrated that the normal intestinal flora is crucial for the
      development of intestinal inflammation. However, due to the complexity of the
      intestinal flora, it has been difficult to design experiments for detection of
      proinflammatory bacterial antigen(s) involved in the pathogenesis of the disease.
      Several studies indicated a potential association of E. coli with IBD. In
      addition, T cell clones of IBD patients were shown to cross react towards
      antigens from different enteric bacterial species and thus likely responded to
      conserved bacterial antigens. We therefore chose highly conserved E. coli
      proteins as candidate antigens for abnormal T cell responses in IBD and used high
      throughput techniques for cloning, expression and purification under native
      conditions of a set of 271 conserved E. coli proteins for downstream immunologic
      studies. RESULTS: As a standardized procedure, genes were PCR amplified and
      cloned into the expression vector pQTEV2 in order to express proteins N
      terminally fused to a seven-histidine-tag. Initial small-scale expression and
      purification under native conditions by metal chelate affinity chromatography
      indicated that the vast majority of target proteins were purified in high yields.
      Targets that revealed low yields after purification probably due to weak
      solubility were shuttled into Gateway (Invitrogen) destination vectors in order
      to enhance solubility by N-terminal fusion of maltose binding protein (MBP), N
      utilizing substance A (NusA), or glutathione S-transferase (GST) to the target
      protein. In addition, recombinant proteins were treated with polymyxin B coated
      magnetic beads in order to remove lipopolysaccharide (LPS). Thus, 73% of the
      targeted proteins could be expressed and purified in large-scale to give soluble
      proteins in the range of 500 microg. CONCLUSION: Here, we report a cost-efficient
      procedure to produce around 200 soluble recombinant E. coli proteins in large
      scale, including removal of LPS by polymyxin B coated beads for subsequent use of
      the proteins in downstream immunological studies.

PMID- 17553161
TI  - PrestOMIC, an open source application for dissemination of proteomic datasets by
      individual laboratories.
AB  - BACKGROUND: Technological advances in mass spectrometry and other detection
      methods are leading to larger and larger proteomics datasets. However, when
      papers describing such information are published the enormous volume of data can
      typically only be provided as supplementary data in a tabular form through the
      journal website. Several journals in the proteomics field, together with the
      Human Proteome Organization's (HUPO) Proteomics Standards Initiative and
      institutions such as the Institute for Systems Biology are working towards
      standardizing the reporting of proteomics data, but just defining standards is
      only a means towards an end for sharing data. Data repositories such as
      ProteomeCommons.org and the Open Proteomics Database allow for public access to
      proteomics data but provide little, if any, interpretation. RESULTS & CONCLUSION:
      Here we describe PrestOMIC, an open source application for storing mass
      spectrometry-based proteomic data in a relational database and for providing a
      user-friendly, searchable and customizable browser interface to share one's data
      with the scientific community. The underlying database and all associated
      applications are built on other existing open source tools, allowing PrestOMIC to
      be modified as the data standards evolve. We then use PrestOMIC to present a
      recently published dataset from our group through our website.

PMID- 17553162
TI  - Generation of FGF reporter transgenic zebrafish and their utility in chemical
      screens.
AB  - BACKGROUND: Fibroblast Growth Factors (FGFs) represent a large family of secreted
      proteins that are required for proper development and physiological processes.
      Mutations in mouse and zebrafish FGFs result in abnormal embryogenesis and
      lethality. A key to understanding the precise role for these factors is to
      determine their spatial and temporal activity during embryogenesis. RESULTS:
      Expression of Dual Specificity Phosphatase 6 (dusp6, also known as Mkp3) is
      controlled by FGF signalling throughout development. The Dusp6 promoter was
      isolated from zebrafish and used to drive expression of destabilized green
      fluorescent protein (d2EGFP) in transgenic embryos (Tg(Dusp6:d2EGFP)). Expression
      of d2EGFP is initiated as early as 4 hours post-fertilization (hpf) within the
      future dorsal region of the embryo, where fgf3 and fgf8 are initially expressed.
      At later stages, d2EGFP is detected within structures that correlate with the
      expression of Fgf ligands and their receptors. This includes the mid-hindbrain
      boundary (MHB), pharyngeal endoderm, otic vesicle, hindbrain, and Kupffer's
      vesicle. The expression of d2EGFP is under the control of FGF signalling as
      treatment with FGF Receptor (FGFR) inhibitors results in the suppression of
      d2EGFP expression. In a pilot screen of commercially available small molecules we
      have evaluated the effectiveness of the transgenic lines to identify specific FGF
      inhibitors within the class of indolinones. These compounds were counter screened
      with the transgenic line Tg(Fli1:EGFP)y1, that serves as an indirect read-out for
      Vascular Endothelial Growth Factor (VEGF) signalling in order to determine the
      specificity between related receptor tyrosine kinases (RTKs). From these assays
      it is possible to determine the specificity of these indolinones towards specific
      RTK signalling pathways. This has enabled the identification of compounds that
      can block specifically the VEGFR or the FGFR signalling pathway. CONCLUSION: The
      generation of transgenic reporter zebrafish lines has allowed direct
      visualization of FGF signalling within the developing embryo. These FGF reporter
      transgenic lines provide a tool to screen for specific compounds that can
      distinguish between two conserved members of the RTK family.

PMID- 17553163
TI  - Cytidine monophospho-N-acetylneuraminic acid hydroxylase (CMAH) mutations
      associated with the domestic cat AB blood group.
AB  - BACKGROUND: The cat has one common blood group with two major serotypes, blood
      type A that is dominant to type B. A rare type AB may also be allelic and is
      suspected to be recessive to A and dominant to B. Cat blood type antigens are
      defined, N-glycolylneuraminic acid (NeuGc) is associated with type A and N
      acetylneuraminic acid (NeuAc) with type B. The enzyme cytidine monophospho-N
      acetylneuraminic acid hydroxylase (CMAH) determines the sugar bound to the red
      cell by converting NeuAc to NeuGc. Thus, mutations in CMAH may cause the A and B
      blood types. RESULTS: Genomic sequence of CMAH from eight cats and the cDNA of
      four cats representing all blood types were analyzed to identify causative
      mutations. DNA variants consistent with the blood types were genotyped in over
      200 cats. Five SNPs and an indel formed haplotypes that were consistent with each
      blood type. CONCLUSION: Mutations in type B cats likely disrupt the gene function
      of CMAH, leading to a predominance of NeuAc. Type AB concordant variants were not
      identified, however, cDNA species suggest an alternative allele that activates a
      downstream start site, leading to a CMAH protein that would be altered at the 5'
      region. The cat AB blood group system is proposed to be designated by three
      alleles, A > aab > b. The A and b CMAH alleles described herein can distinguish
      type A and type B cats without blood sample collections. CMAH represents the
      first blood group gene identified outside of non-human primates and humans.

PMID- 17553164
TI  - Androgen-regulated genes differentially modulated by the androgen receptor
      coactivator L-dopa decarboxylase in human prostate cancer cells.
AB  - BACKGROUND: The androgen receptor is a ligand-induced transcriptional factor,
      which plays an important role in normal development of the prostate as well as in
      the progression of prostate cancer to a hormone refractory state. We previously
      reported the identification of a novel AR coactivator protein, L-dopa
      decarboxylase (DDC), which can act at the cytoplasmic level to enhance AR
      activity. We have also shown that DDC is a neuroendocrine (NE) marker of prostate
      cancer and that its expression is increased after hormone-ablation therapy and
      progression to androgen independence. In the present study, we generated
      tetracycline-inducible LNCaP-DDC prostate cancer stable cells to identify DDC
      downstream target genes by oligonucleotide microarray analysis. RESULTS:
      Comparison of induced DDC overexpressing cells versus non-induced control cell
      lines revealed a number of changes in the expression of androgen-regulated
      transcripts encoding proteins with a variety of molecular functions, including
      signal transduction, binding and catalytic activities. There were a total of 35
      differentially expressed genes, 25 up-regulated and 10 down-regulated, in the DDC
      overexpressing cell line. In particular, we found a well-known androgen induced
      gene, TMEPAI, which wasup-regulated in DDC overexpressing cells, supporting its
      known co-activation function. In addition, DDC also further augmented the
      transcriptional repression function of AR for a subset of androgen-repressed
      genes. Changes in cellular gene transcription detected by microarray analysis
      were confirmed for selected genes by quantitative real-time RT-PCR. CONCLUSION:
      Taken together, our results provide evidence for linking DDC action with AR
      signaling, which may be important for orchestrating molecular changes responsible
      for prostate cancer progression.

PMID- 17553166
TI  - The effect of ABCA1 gene polymorphisms on ischaemic stroke risk and relationship
      with lipid profile.
AB  - BACKGROUND: Ischaemic stroke is a common disorder with genetic and environmental
      components contributing to overall risk. Atherothromboembolic abnormalities,
      which play a crucial role in the pathogenesis of ischaemic stroke, are often the
      end result of dysregulation of lipid metabolism. The ATP Binding Cassette
      Transporter (ABCA1) is a key gene involved in lipid metabolism. It encodes the
      cholesterol regulatory efflux protein which mediates the transfer of cellular
      phospholipids and cholesterol to acceptor apolipoproteins such as apolipoprotein
      A-I (ApoA-I). Common polymorphisms in this gene affect High Density Lipoprotein
      Cholesterol (HDL-C) and Apolipoprotein A-I levels and so influence the risk of
      atherosclerosis. This study has assessed the distribution of ABCA1 polymorphisms
      and haplotype arrangements in patients with ischaemic stroke and compared them to
      an appropriate control group. It also examined the relationship of these
      polymorphisms with serum lipid profiles in cases and controls. METHODS: We
      studied four common polymorphisms in ABCA1 gene: G/A-L158L, G/A-R219K, G/A-G316G
      and G/A-R1587K in 400 Caucasian ischaemic stroke patients and 487 controls.
      Dynamic Allele Specific Hybridisation (DASH) was used as the genotyping assay.
      RESULTS: Genotype and allele frequencies of all polymorphisms were similar in
      cases and controls, except for a modest difference in the ABCA1 R219K allele
      frequency (P-value = 0.05). Using the PHASE2 program, haplotype frequencies for
      the four loci (158, 219, 316, and 1587) were estimated in cases and controls.
      There was no significant difference in overall haplotypes arrangement in patients
      group compared to controls (p = 0.27). 2211 and 1211 haplotypes (1 = common
      allele, 2 = rare allele) were more frequent in cases (p = 0.05). Adjusted ORs
      indicated 40% and 46% excess risk of stroke for these haplotypes respectively.
      However, none of the adjusted ORs were statistically significant. Individuals who
      had R219K "22" genotype had a higher LDL level (p = 0.001). CONCLUSION: Our study
      does not support a major role for the ABCA1 gene as a risk factor for ischaemic
      stroke. Some haplotypes may confer a minor amount of increased risk or
      protection. Polymorphisms in this gene may influence serum lipid profile.

PMID- 17553165
TI  - Identification of novel androgen receptor target genes in prostate cancer.
AB  - BACKGROUND: The androgen receptor (AR) plays critical roles in both androgen
      dependent and castrate-resistant prostate cancer (PCa). However, little is known
      about AR target genes that mediate the receptor's roles in disease progression.
      RESULTS: Using Chromatin Immunoprecipitation (ChIP) Display, we discovered 19
      novel loci occupied by the AR in castrate resistant C4-2B PCa cells. Only four of
      the 19 AR-occupied regions were within 10-kb 5'-flanking regulatory sequences.
      Three were located up to 4-kb 3' of the nearest gene, eight were intragenic and
      four were in gene deserts. Whereas the AR occupied the same loci in C4-2B
      (castrate resistant) and LNCaP (androgen-dependent) PCa cells, differences
      between the two cell lines were observed in the response of nearby genes to
      androgens. Among the genes strongly stimulated by DHT in C4-2B cells--D
      dopachrome tautomerase (DDT), Protein kinase C delta (PRKCD), Glutathione S-
      transferase theta 2 (GSTT2), Transient receptor potential cation channel
      subfamily V member 3 (TRPV3), and Pyrroline-5-carboxylate reductase 1 (PYCR1)-
      most were less strongly or hardly stimulated in LNCaP cells. Another AR target
      gene, ornithine aminotransferase (OAT), was AR-stimulated in a ligand-independent
      manner, since it was repressed by AR siRNA knockdown, but not stimulated by DHT.
      We also present evidence for in vivo AR-mediated regulation of several genes
      identified by ChIP Display. For example, PRKCD and PYCR1, which may contribute to
      PCa cell growth and survival, are expressed in PCa biopsies from primary tumors
      before and after ablation and in metastatic lesions in a manner consistent with
      AR-mediated stimulation. CONCLUSION: AR genomic occupancy is similar between
      LNCaP and C4-2B cells and is not biased towards 5' gene flanking sequences. The
      AR transcriptionally regulates less than half the genes nearby AR-occupied
      regions, usually but not always, in a ligand-dependent manner. Most are
      stimulated and a few are repressed. In general, response is stronger in C4-2B
      compared to LNCaP cells. Some of the genes near AR-occupied regions appear to be
      regulated by the AR in vivo as evidenced by their expression levels in prostate
      cancer tumors of various stages. Several AR target genes discovered in the
      present study, for example PRKCD and PYCR1, may open avenues in PCa research and
      aid the development of new approaches for disease management.

PMID- 17553167
TI  - MPHASYS: a mouse phenotype analysis system.
AB  - BACKGROUND: Systematic, high-throughput studies of mouse phenotypes have been
      hampered by the inability to analyze individual animal data from a multitude of
      sources in an integrated manner. Studies generally make comparisons at the level
      of genotype or treatment thereby excluding associations that may be subtle or
      involve compound phenotypes. Additionally, the lack of integrated, standardized
      ontologies and methodologies for data exchange has inhibited scientific
      collaboration and discovery. RESULTS: Here we introduce a Mouse Phenotype
      Analysis System (MPHASYS), a platform for integrating data generated by studies
      of mouse models of human biology and disease such as aging and cancer. This
      computational platform is designed to provide a standardized methodology for
      working with animal data; a framework for data entry, analysis and sharing; and
      ontologies and methodologies for ensuring accurate data capture. We describe the
      tools that currently comprise MPHASYS, primarily ones related to mouse pathology,
      and outline its use in a study of individual animal-specific patterns of multiple
      pathology in mice harboring a specific germline mutation in the DNA repair and
      transcription-specific gene Xpd. CONCLUSION: MPHASYS is a system for analyzing
      multiple data types from individual animals. It provides a framework for
      developing data analysis applications, and tools for collecting and distributing
      high-quality data. The software is platform independent and freely available
      under an open-source license 1.

PMID- 17553168
TI  - Developing algorithms for healthcare insurers to systematically monitor surgical
      site infection rates.
AB  - BACKGROUND: Claims data provide rapid indicators of SSIs for coronary artery
      bypass surgery and have been shown to successfully rank hospitals by SSI rates.
      We now operationalize this method for use by payers without transfer of protected
      health information, or any insurer data, to external analytic centers. RESULTS:
      We performed a descriptive study testing the operationalization of software for
      payers to routinely assess surgical infection rates among hospitals where
      enrollees receive cardiac procedures. We developed five SAS programs and a user
      manual for direct use by health plans and payers. The manual and programs were
      refined following provision to two national insurers who applied the programs to
      claims databases, following instructions on data preparation, data validation,
      analysis, and verification and interpretation of program output. A final set of
      programs and user manual successfully guided health plan programmer analysts to
      apply SSI algorithms to claims databases. Validation steps identified common
      problems such as incomplete preparation of data, missing data, insufficient
      sample size, and other issues that might result in program failure. Several user
      prompts enabled health plans to select time windows, strata such as insurance
      type, and the threshold number of procedures performed by a hospital before
      inclusion in regression models assessing relative SSI rates among hospitals. No
      health plan data was transferred to outside entities. Programs, on default
      settings, provided descriptive tables of SSI indicators stratified by hospital,
      insurer type, SSI indicator (inpatient, outpatient, antibiotic), and six-month
      period. Regression models provided rankings of hospital SSI indicator rates by
      quartiles, adjusted for comorbidities. Programs are publicly available without
      charge. CONCLUSION: We describe a free, user-friendly software package that
      enables payers to routinely assess and identify hospitals with potentially high
      SSI rates complicating cardiac procedures.

PMID- 17553169
TI  - A novel and ancient group of type I keratins with members in bichir, sturgeon and
      gar.
AB  - BACKGROUND: Vertebrate epithelial cells typically express a specific set of
      keratins. In teleosts, keratins are also present in a variety of mesenchymal
      cells, which usually express vimentin. Significantly, our previous studies
      revealed that virtually all known teleost keratins evolved independently from
      those present in terrestrial vertebrates. To further elucidate the evolutionary
      scenario that led to the large variety of keratins and their complex expression
      patterns in present day teleosts, we have investigated their presence in bichir,
      sturgeon and gar. RESULTS: We have discovered a novel group of type I keratins
      with members in all three of these ancient ray-finned fish, but apparently no
      counterparts are present in any other vertebrate class so far investigated,
      including the modern teleost fish. From sturgeon and gar we sequenced one and
      from bichir two members of this novel keratin group. By complementary keratin
      blot-binding assays and peptide mass fingerprinting using MALDI-TOF mass
      spectrometry, in sturgeon we were able to assign the sequence to a prominent
      protein spot, present exclusively in a two-dimensionally separated cytoskeletal
      preparation of skin, thus identifying it as an epidermally expressed type I
      keratin. In contrast to the other keratins we have so far sequenced from bichir,
      sturgeon and gar, these new sequences occupy a rather basal position within the
      phylogenetic tree of type I keratins, in a close vicinity to the keratins we
      previously cloned from river lamprey. CONCLUSION: Thus, this new K14 group seem
      to belong to a very ancient keratin branch, whose functional role has still to be
      further elucidated. Furthermore, the exclusive presence of this keratin group in
      bichir, sturgeon and gar points to the close phylogenetic relationship of these
      ray- finned fish, an issue still under debate among taxonomists.

PMID- 17553170
TI  - Replacement of the essential Dictyostelium Arp2 gene by its Entamoeba homologue
      using parasexual genetics.
AB  - BACKGROUND: Cell motility is an essential feature of the pathogenesis and
      morbidity of amoebiasis caused by Entamoeba histolytica. As motility depends on
      cytoskeletal organisation and regulation, a study of the molecular components
      involved is key to a better understanding of amoebic pathogenesis. However,
      little is known about the physiological roles, interactions and regulation of the
      proteins of the Entamoeba cytoskeleton. RESULTS: We have established a genetic
      strategy that uses parasexual genetics to allow essential Dictyostelium
      discoideum genes to be manipulated and replaced with modified or tagged
      homologues. Our results show that actin related protein 2 (Arp2) is essential for
      survival, but that the Dictyostelium protein can be complemented by E.
      histolytica Arp2, despite the presence of an insertion of 16 amino acids in an
      otherwise highly conserved protein. Replacement of endogenous Arp2 with myc
      tagged Entamoeba or Dictyostelium Arp2 has no obvious effects on growth and the
      protein incorporates effectively into the Arp2/3 complex. CONCLUSION: We have
      established an effective two-step method for replacing genes that are required
      for survival. Our protocol will allow such genes to be studied far more easily,
      and also allows an unambiguous demonstration that particular genes are truly
      essential. In addition, cells in which the Dictyostelium Arp2 has been replaced
      by the Entamoeba protein are potential targets for drug screens.

PMID- 17553171
TI  - RAD marker microarrays enable rapid mapping of zebrafish mutations.
AB  - We constructed a restriction site associated DNA (RAD) marker microarray to
      facilitate rapid genetic mapping of zebrafish mutations. Using these microarrays
      with a bulk segregant approach, we localized previously unmapped mutations to
      genomic regions just a few centiMorgans in length. Furthermore, we developed an
      approach to assay individual RAD markers in pooled populations and refined one
      region. The RAD approach is highly effective for genetic mapping in zebrafish and
      is an attractive option for mapping in other organisms.

PMID- 17553172
TI  - Human neuronal cell protein responses to Nipah virus infection.
AB  - BACKGROUND: Nipah virus (NiV), a recently discovered zoonotic virus infects and
      replicates in several human cell types. Its replication in human neuronal cells,
      however, is less efficient in comparison to other fully susceptible cells. In the
      present study, the SK-N-MC human neuronal cell protein response to NiV infection
      is examined using proteomic approaches. RESULTS: Method for separation of the NiV
      infected human neuronal cell proteins using two-dimensional polyacrylamide gel
      electrophoresis (2D-PAGE) was established. At least 800 protein spots were
      resolved of which seven were unique, six were significantly up-regulated and
      eight were significantly down-regulated. Six of these altered proteins were
      identified using mass spectrometry (MS) and confirmed using MS/MS. The
      heterogenous nuclear ribonucleoprotein (hnRNP) F, guanine nucleotide binding
      protein (G protein), voltage-dependent anion channel 2 (VDAC2) and cytochrome bc1
      were present in abundance in the NiV-infected SK-N-MC cells in contrast to hnRNPs
      H and H2 that were significantly down-regulated. CONCLUSION: Several human
      neuronal cell proteins that are differentially expressed following NiV infection
      are identified. The proteins are associated with various cellular functions and
      their abundance reflects their significance in the cytopathologic responses to
      the infection and the regulation of NiV replication. The potential importance of
      the ratio of hnRNP F, and hnRNPs H and H2 in regulation of NiV replication, the
      association of the mitochondrial protein with the cytopathologic responses to the
      infection and induction of apoptosis are highlighted.

PMID- 17553173
TI  - Robust interlaboratory reproducibility of a gene expression signature measurement
      consistent with the needs of a new generation of diagnostic tools.
AB  - BACKGROUND: The increasing use of DNA microarrays in biomedical research,
      toxicogenomics, pharmaceutical development, and diagnostics has focused attention
      on the reproducibility and reliability of microarray measurements. While the
      reproducibility of microarray gene expression measurements has been the subject
      of several recent reports, there is still a need for systematic investigation
      into what factors most contribute to variability of measured expression levels
      observed among different laboratories and different experimenters. RESULTS: We
      report the results of an interlaboratory comparison of gene expression array
      measurements on the same microarray platform, in which the RNA amplification and
      labeling, hybridization and wash, and slide scanning were each individually
      varied. Identical input RNA was used for all experiments. While some sources of
      variation have measurable influence on individual microarray signals, they showed
      very low influence on sample-to-reference ratios based on averaged triplicate
      measurements in the two-color experiments. RNA labeling was the largest
      contributor to interlaboratory variation. CONCLUSION: Despite this variation,
      measurement of one particular breast cancer gene expression signature in three
      different laboratories was found to be highly robust, showing a high
      intralaboratory and interlaboratory reproducibility when using strictly
      controlled standard operating procedures.

PMID- 17553174
TI  - Impact of ambient air pollution on gestational age is modified by season in
      Sydney, Australia.
AB  - BACKGROUND: The effect of individual pollutants and the period(s) during
      pregnancy when pollutant levels are likely to have most impact on preterm birth
      is not clear. We evaluated the effect of prenatal exposure to six common urban
      air pollutants in the Sydney metropolitan area on preterm birth. METHODS: We
      obtained information on all births in metropolitan Sydney between January 1, 1998
      and December 31, 2000. For each birth, exposure to each air pollutant was
      estimated for the first trimester, the three months preceding birth, the first
      month after the estimated date of conception and the month prior to delivery.
      Gestational age was analysed as a categorical variable in logistic regression
      models. RESULTS: There were 123,840 singleton births in Sydney in 1998-2000 and
      4.9% were preterm. Preterm birth was significantly associated with maternal age,
      maternal smoking, male infant, indigenous status and first pregnancy. Air
      pollutant levels in the month and three months preceding birth had no significant
      effect on preterm birth after adjusting for maternal and infant covariates. Ozone
      levels in the first trimester of pregnancy and spring months of conception and
      sulphur dioxide were associated with increased risks for preterm births. Nitrogen
      dioxide was associated with a decreased risk of preterm births. CONCLUSION: We
      found more protective than harmful associations between ambient air pollutants
      and preterm births with most associations non-significant. In view of these
      inconsistent associations, it is important to interpret the harmful effects with
      caution. If our results are confirmed by future studies then it will be
      imperative to reduce Sydney's already low air pollution levels even further.

PMID- 17553175
TI  - Exceptionally high incidence of symptomatic grade 2-5 radiation pneumonitis after
      stereotactic radiation therapy for lung tumors.
AB  - BACKGROUND: To determine the usefulness of dose volume histogram (DVH) factors
      for predicting the occurrence of radiation pneumonitis (RP) after application of
      stereotactic radiation therapy (SRT) for lung tumors, DVH factors were measured
      before irradiation. METHODS: From May 2004 to April 2006, 25 patients were
      treated with SRT at the University of Tokyo Hospital. Eighteen patients had
      primary lung cancer and seven had metastatic lung cancer. SRT was given in 6-7
      fields with an isocenter dose of 48 Gy in four fractions over 5-8 days by linear
      accelerator. RESULTS: Seven of the 25 patients suffered from RP of symptomatic
      grade 2-5 according to the NCI-CTC version 3.0. The overall incidence rate of RP
      grade2 or more was 29% at 18 months after completing SRT and three patients died
      from RP. RP occurred at significantly increased frequencies in patients with
      higher conformity index (CI) (p = 0.0394). Mean lung dose (MLD) showed a
      significant correlation with V5-V20 (irradiated lung volume) (p < 0.001) but
      showed no correlation with CI. RP did not statistically correlate with MLD. MLD
      had the strongest correlation with V5. CONCLUSION: Even in SRT, when large
      volumes of lung parenchyma are irradiated to such high doses as the minimum dose
      within planning target volume, the incidence of lung toxicity can become high.

PMID- 17553176
TI  - Seroepidemiology of hepatitis A in voluntary blood donors from Pune, western
      India (2002 and 2004-2005).
AB  - Recently, a changing pattern of hepatitis A epidemiology has been reported in the
      Indian population indicating a rise in the rate of hepatitis A infection among
      adults. The study's objective was to assess anti-HAV prevalence in voluntary
      blood donors from middle and high socioeconomic strata. Serum samples collected
      from voluntary blood donors from Pune city and its suburbs in the years 2002 and
      2004-2005 were tested for anti-HAV IgG antibodies. Serum samples collected during
      2004-2005 were examined for anti-HAV IgM antibodies. Positive samples were tested
      for HAV-RNA. Agewise anti-HAV positivity was significantly low in adults aged 18
      25 years (90.4%) compared to those aged >25 years (97.4%) (P<0.01). A decline in
      anti-HAV prevalence was significant in 2004-2005 compared to that in 2002 (96.5%
      vs. 92.1%) (P<0.01). Overall, in both adult age groups, the proportion of anti
      HAV positivity was remarkably low in the high socioeconomic group (HSG) (88.96%)
      compared to that of the middle socioeconomic group (MSG) (95.86%) (P<0.01). Anti
      HAV IgM positivity was not significant (~1%), however, presence of HAV-RNA in one
      of the samples indicated the possibility of horizontal transmission of HAV.
      Increase in seronegativity to HAV in HSG implicates a rise in the susceptible
      pool and indicates the need for vaccination against hepatitis A.

PMID- 17553177
TI  - Cercarial dermatitis and lake eutrophication in south-central Chile.
AB  - Cercarial dermatitis is caused by exposure to the cercariae of schistosome
      species which have birds or mammals as their definitive hosts. A public alarm was
      raised in the summer of 2004 when this parasitic disease was observed for the
      first time in south-central Chile at Laguna Chica de San Pedro (36 degrees 51''
      S, 73 degrees 05'' W). Swimmers at this eutrophic lake were surveyed in order to
      estimate the amount of cercarial dermatitis in the area; participants were
      observed during the summers of 2004 and 2005 for clinical signs of cercarial
      dermatitis and 25 Chilina dombeyana snails were collected monthly from Laguna
      Chica de San Pedro during one year and then examined for animal schistosome
      cercariae. We found that 3% of the swimmers had pruritic maculopapular rashes on
      their legs, arms, necks, or other body parts and that between 9.1% (May 2006) and
      52.4% (November 2004) of the snails examined were infected with the bird
      schistosome cercariae Trichobilharzia sp.

PMID- 17553178
TI  - Population-based study of human papillomavirus infection and cervical neoplasia
      in Athens, Greece.
AB  - The aim of our study is to describe the prevalence of the different HPV types in
      women with pre-neoplastic lesions of the cervix in Greece. Cervical scrapes from
      841 women were obtained for both cytological evaluation and analysis for the
      presence of HPV DNA. PCR was performed on specimens from these 841 women. The Pap
      test results were normal or showed benign cellular changes in 45.8% of the women,
      atypical squamous cells of undetermined significance (ASCUS) in 23.2%, low-grade
      squamous intra-epithelial lesion (LSIL) in 27.9% and high-grade squamous intra
      epithelial lesion (HSIL) in 3.1%. HPV DNA was demonstrated in 23.6% of
      cytologically normal women. We detected HPV in 60% of the total samples. Of
      these, HPV-16 was the most common HPV DNA detected. Interestingly, HPV-58 was
      inversely correlated with positive cytological findings. A clear pattern of
      decreasing prevalence of HPV with age was also observed. Our results indicate
      that HPV infections, especially those with HPV-16, represent a significant public
      health concern in Greece.

PMID- 17553179
TI  - Semmelweis and the aetiology of puerperal sepsis 160 years on: an historical
      review.
AB  - It is generally accepted that Professor Ignaz Semmelweis was the first to
      identify the mode of transmission of puerperal sepsis. However no appropriate
      statistical analysis of Semmelweis's data supporting his theory has been
      reported. Mean annual percent maternal mortality rates for the Allgemeines
      Krankenhaus and Dublin Maternity Hospitals (1784-1858) were analysed. The
      introduction of pathological anatomy at the Allgemeines Krankenhaus in 1823 was
      associated with increased mortality. After 1840 maternal mortality was higher in
      Clinic 1 which was staffed by male obstetricians and medical students who, unlike
      the midwives in Clinic 2, attended autopsies. The introduction of chlorine
      washing of the male clinicians' hands in Clinic 1 by Semmelweis in 1847 reduced
      mortality, whereas the cessation of handwashing after Semmelweis left Vienna in
      1850 was associated with increased mortality. This statistical analysis supports
      Semmelweis's hypothesis that 'the cadaveric particles adhering to the hand had
      ... caused the preponderant mortality in the first Clinic'.

PMID- 17553180
TI  - Transcriptome analysis during the process of in vitro differentiation of
      Leishmania donovani using genomic microarrays.
AB  - Leishmania donovani causes visceral disease (kala-azar), a major health problem
      throughout the tropics with 500 000 new cases every year. Leishmania
      differentiates from the promastigote to the amastigote form to establish
      infection in a mammalian host. To understand the process of differentiation, we
      assessed the global variation in gene expression in promastigotes, an
      intermediate stage of differentiation (PA24) and axenic amastigotes in culture
      using an L. donovani genomic microarray with 4224 clones printed in triplicate.
      During an intermediate stage of differentiation 24 h after shifting the
      promastigotes into amastigotes (PA24), there were 41 (approximately 1%) clones
      with expression > or = 2.0-fold higher than promastigotes, whereas in terminally
      differentiated amastigotes there were 130 (approximately 3%) such clones. Of
      particular interest were certain genes that exhibited a transient increase or
      decrease in expression at the PA24 stage. Kinases showed a transient increase,
      and surface molecules, PSA and amino acid permease, were prominent clones among
      those showing a brief decrease at the PA24 stage. The microarray results have
      been validated using Northern blots or RT-PCR. In summary, our results provide
      important clues about the genes involved in the differentiation process of L.
      donovani that may contribute to virulence.

PMID- 17553181
TI  - Radiological anatomy of the anterior ethmoidal artery for functional endoscopic
      sinus surgery.
AB  - AIM: This study investigated the extent to which the anterior ethmoidal artery
      and anterior ethmoidal foramen could be reliably identified on routine coronal
      sinus computed tomography scans. Where they could be identified, the relationship
      of these structures with the vertical height of the skull base, and their
      distance from an anterior landmark, were measured. METHODS: Fifty consecutive
      coronal sinus computed tomography scans were viewed independently by two
      observers. Scans were reviewed when the observers' opinions differed. RESULTS:
      Inter-observer concordance was high. The anterior ethmoidal foramen was
      visualised in 95 per cent of cases bilaterally and in the remaining 5 per cent
      unilaterally. The anterior ethmoidal artery was visualised in 33 per cent of
      scans. The anterior ethmoidal foramen was at skull base level in 72 per cent of
      sides studied, and below it in the remainder. The distance from the lacrimal
      crest to the anterior ethmoidal foramen was 22.4 mm (mean; standard deviation
      3.7). CONCLUSION: The anterior ethmoidal foramen is a reliable landmark on
      coronal computed tomography scans of the paranasal sinuses. From this, the
      position of the anterior ethmoidal artery can be inferred.

PMID- 17553182
TI  - Nasal septal perforation and antiphospholipid syndrome (Hughes syndrome).
AB  - We present the case of a 19-year-old woman who developed a nasal septal
      perforation and atrophic rhinitis following septal surgery. During the subsequent
      five years, she also experienced intermittent episodes of swelling and ischaemia
      of the left foot, as well as livedo reticularis. Ultimately, haematological
      investigations revealed the presence of lupus anticoagulant and elevated
      antiphospholipid immunoglobulin M levels. A diagnosis of antiphospholipid
      syndrome (Hughes syndrome) was made.A search of the literature revealed that
      nasal septal perforation has been described in up to 0.8 per cent of patients
      with antiphospholipid syndrome. However, it is undescribed in the
      otorhinolaryngological literature. The impact of this syndrome on
      otorhinolaryngology practice is examined.

PMID- 17553183
TI  - Morbidity after adenotonsillectomy for paediatric obstructive sleep apnoea
      syndrome: waking up to a pragmatic approach.
AB  - INTRODUCTION: Adenotonsillectomy is successful at eliminating airway obstruction
      in the majority of otherwise normal children with obstructive sleep apnoea
      syndrome. Children with this condition are at significantly higher risk of post
      operative respiratory complications. Identifying children at risk of post
      operative respiratory complications after adenotonsillectomy for obstructive
      sleep apnoea syndrome remains a challenge for clinicians, especially those at
      district general hospitals. AIM: To review the evidence and to proffer a
      pragmatic approach to diagnosis and management, by classifying those at risk of
      post-operative respiratory complications into different risk subsets, with
      guidelines for management. CONCLUSION: Patients in the high risk group should be
      operated upon at paediatric specialist centres with intensive care facilities.
      Those in the moderate risk group may undergo adenotonsillectomy at their district
      general hospital, provided facilities for administering continuous positive
      airway pressure are available on-site. Most children with obstructive sleep
      apnoea syndrome may be classified as low risk candidates and may safely be
      operated upon at their local district general hospital.

PMID- 17553184
TI  - Bacterial biofilm adherence to middle-ear ventilation tubes: scanning electron
      micrograph images and literature review.
AB  - INTRODUCTION: The organisms that cause many device-related and other chronic
      infections actually grow in biofilms in or on these devices. We sought to examine
      the role of biofilm formation in chronic middle-ear ventilation tube infection.
      CASE REPORT: Scanning electron micrograph images are presented which demonstrate
      biofilm on a middle-ear ventilation tube removed from a five-year-old child's
      chronically discharging ear. A review of the relevant international literature
      explores the role of biofilms in chronic infection and discusses potential
      intervention strategies. CONCLUSION: Biofilms may be responsible for chronic
      middle-ear ventilation tube infection that resists treatment with conventional
      antibiotics.

PMID- 17553185
TI  - Navigational systems in rhinology: should we all be using them?
AB  - The proximity of the paranasal sinuses to important anatomical structures creates
      the potential for serious complications following endoscopic sinus surgery. Over
      recent years, navigational systems have been developed and are increasingly being
      used by some centres. We summarise the history and principles of navigational
      sinus surgery, review the medical literature on the topic, and try to assess what
      role navigational systems should play in modern day rhinology practice.

PMID- 17553186
TI  - Combined approach tympanoplasty for cholesteatoma: impact of middle-ear
      endoscopy.
AB  - OBJECTIVE: The aims of this study were (1) to explore whether the experience at
      the Radcliffe Infirmary (Oxford, UK) supported the use of combined approach
      tympanoplasty for cholesteatoma, by determining the rate of disease at subsequent
      surgery, and (2) to assess whether this rate differed from findings reported
      elsewhere in the literature, possibly due to the effect of using an oto
      endoscope. STUDY DESIGN: Retrospective case review, with data entered
      prospectively for operations performed by a single surgeon. SETTING: Tertiary
      referral hospital. PATIENTS: Between January 1998 and December 2004 inclusive, 66
      patients underwent 68 primary procedures, with data available for all 'second
      looks'. INTERVENTIONS: Diagnostic and therapeutic operations for cholesteatoma
      were performed. MAIN OUTCOME MEASURES: All patients in this study attended follow
      up and underwent a second look operation, during which the rate of residual and
      recurrent cholesteatoma was determined. An oto-endoscope was used at all primary
      and subsequent surgery. RESULTS: The mean interval between the first and second
      combined approach tympanoplasty procedures was 16 months, and that between the
      second and third such procedures was 19 months (10 patients). One patient
      underwent a fourth combined approach tympanoplasty procedure, 17 months after a
      third such procedure. The rate of cholesteatoma at second combined approach
      tympanoplasty was 20.6 per cent (14/68); this was judged to be residual in 10
      ears (14.7 per cent) and to be recurrent, with the redevelopment of retraction
      pockets, in four ears (5.9 per cent). The rate of cholesteatoma at third combined
      approach tympanoplasty was 20 per cent (two of 10); of these two, one patient had
      a small pearl in the middle ear removed with the aid of a potassium titanyl
      phosphate laser. There was no disease present in one patient at a fourth combined
      approach tympanoplasty. Only four patients required a modified radical
      mastoidectomy. CONCLUSION: Cholesteatoma remains a disease with significant
      morbidity. Endoscope-assisted surgery may decrease the morbidity of second look
      surgery and may improve the clearance of disease in appropriately selected
      patients.

PMID- 17553187
TI  - Suture techniques in nasal tip sculpture: current concepts.
AB  - OBJECTIVES: The three-dimensional anatomy and conspicuous location of the nasal
      tip makes it one of the most challenging sites of facial plastic surgery. This
      article reviews literature on nasal tip sculpture using suture techniques, as
      well as the authors' own experience. METHODS: A search was conducted using
      Pubmed, the Google internet search engine and the authors' files, using the
      keywords 'nasal tip', 'suture', 'rhinoplasty' and 'septorhinoplasty'. RESULTS:
      Common nasal tip suture techniques and suture algorithms are presented, along
      with a summary of the indications and side effects of each technique.
      CONCLUSIONS: Predictable long-term results are more likely to occur with minimal
      local tissue excision. Suture techniques remodel the shape of the nasal tip by
      altering the configuration of, and the relationship between, the tip cartilages
      and their supporting structures; they also preserve nasal tip anatomy and limit
      resection. Intra-operatively, the effects are immediately visible, and can be
      adjusted or reversed. Tip sutures should therefore be considered instead of
      tissue excision whenever possible.

PMID- 17553188
TI  - Cervical extraskeletal Ewing's sarcoma: case report demonstrating radiological
      features and management.
AB  - BACKGROUND: Extraskeletal Ewing's sarcoma is a rare tumour of mesenchymal origin,
      which is histologically similar to primary osseous Ewing's sarcoma. The majority
      of cases have been reported in the lower limb and paravertebral region, with a
      few cases reported in the neck. METHODS: We report a patient with extraskeletal
      Ewing's sarcoma presenting with a right-sided neck mass, vocal fold palsy and T1
      nerve root involvement. The detection of characteristic features on computed
      tomography and magnetic resonance imaging scans, in conjunction with histological
      analysis, was required to make the diagnosis. RESULTS: Radiological imaging
      demonstrated that the tumour was infiltrating through the neural exit foramina of
      the lower cervical nerve roots, with encasement of the vertebral artery. The
      patient was managed with combination chemotherapy for systemic control and
      irradiation for local control. CONCLUSION: Extraskeletal Ewing's sarcoma has a
      propensity to occur in a paravertebral location, being found rarely in the
      cervical region, and has a predilection to infiltrate through neural exit
      formina. Computed tomography and magnetic resonance imaging are helpful in the
      diagnosis of this rare tumour.

PMID- 17553191
TI  - Canadian dietitians' understanding of non-dieting approaches in weight
      management.
AB  - PURPOSE: How Canadian dietitians define and use non-dieting and size acceptance
      approaches (SAAs) in the context of weight management was explored. METHODS:
      Fifteen focus groups with 104 dietitians were conducted in seven Canadian cities.
      Questions were designed to explore participants' understanding and use of non
      dieting and SAAs, including counselling goals, techniques, and outcome measures.
      Sessions were tape-recorded, transcribed verbatim, coded, and analyzed using
      qualitative methods. RESULTS: Participants generally agreed that non-dieting
      involves promoting healthy lifestyles and avoiding restrictive diets.
      Participants also agreed that size acceptance means accepting all body shapes and
      sizes and promoting comfort with one's body. Many dietitians said they use size
      acceptance only with appropriate clients, most often with those who are lighter
      or without other health risks. Others said that size acceptance, by definition,
      is appropriate for everyone. Opinions varied about the appropriateness of
      teaching portion sizes or using meal plans, and whether weight loss could be a
      goal of non-dieting and SAAs. CONCLUSIONS: Views on the usefulness of non-dieting
      and size acceptance strategies in weight management counselling were related, at
      least partially, to the different understanding that dietitians had of these
      approaches. Terminology needs to be clarified when we speak about non-dieting and
      SAAs. The varied understanding about these concepts should help dietitians
      reflect on their own perspectives and practice.

PMID- 17553192
TI  - Food insecurity and dietary intake of immigrant food bank users.
AB  - PURPOSE: The degree of food insecurity and dietary intake was examined in adult
      Colombians who are new immigrants to Canada and use a food bank. METHODS: In
      person surveys were conducted on a convenience sample of 77 adult Colombian
      immigrant food bank users in London, Ontario. Degree of food insecurity was
      measured by the Radimer/Cornell questionnaire, food intakes by 24-hour recall,
      sociodemographics, and questionnaires about changes in dietary patterns before
      and after immigration. RESULTS: Thirty-six men and 41 women participated in the
      study. Despite being highly educated, all respondents had experienced some form
      of food insecurity within the previous 30 days. The degree of food insecurity
      seems to be inversely associated with income and length of residency in Canada.
      Total daily energy intake was low, with a mean value of 1,568.3 +/- 606.0 kcal
      (6,217.5 +/- 2,336.4 kJ). In particular, a large proportion of participants
      consumed a diet low in fruits and vegetables (73%) and milk and dairy products
      (58%). CONCLUSIONS: Colombian immigrant food bank users new to Canada experience
      various degrees of food insecurity, which is associated with inadequate food
      intake. Interventions are needed to assist this population with adapting to
      society while concurrently sustaining healthy eating patterns.

PMID- 17553193
TI  - The registered dietitian in primary care: the Hamilton experience.
AB  - The Hamilton Health Service Organization Nutrition Program integrates nine
      registered dietitians (RDs) into the offices of 80 family physicians (FPs) at 50
      sites in Hamilton, Ontario. The program is based on a shared care model, in which
      FPs and RDs work collaboratively to provide nutrition services aimed at
      prevention, treatment, and management of nutrition-related problems. In addition
      to their clinical role, dietitians in the program are involved in health
      promotion, disease prevention and early intervention strategies,
      interdisciplinary collaboration, building links with community services, and
      research. The RDs' specialized knowledge, skills, and experience allow them to
      provide a wide range of services that complement and augment those of the FP.
      This model is consistent with Canadian health care reform recommendations and
      offers significant benefits for both health care providers and consumers.

PMID- 17553194
TI  - Process evaluation of bringing nutrition screening to seniors in Canada (BNSS).
AB  - Although nutrition risk is prevalent in Canadian older adults, the process of
      screening must be considered before nationwide programs can be recommended. A
      process evaluation of the Bringing Nutrition Screening to Seniors in Canada
      demonstration project was completed. Through the use of the 15-item Seniors in
      the Community: Risk Evaluation for Eating and Nutrition (SCREEN(c))
      questionnaire, risk was identified in convenience samples of 1,196 community
      living older adults recruited from five Canadian communities. All at-risk
      participants were offered referrals to community resources. Telephone follow-up
      of at-risk participants occurred after screening. Telephone interviews with
      screening administrators and older adults revealed screening benefits and
      challenges. Nutrition risk occurred in 38.9% of the sample. Most participants
      found screening helpful. Among the at-risk group (n=465), 39% accepted referrals
      for additional services. Older adults provided several reasons for refusing
      referrals, including denial of risk. Dietitian services were an identified gap,
      as were prevention-level resources. Nutrition risk is prevalent and older adults
      can benefit from screening. Training, ongoing support, and prioritization
      (policy, time, and money) are needed for sustainable screening programs. Before
      implementation of a nationwide screening program, sufficient and appropriate
      community resources are required, as is a national strategy for screening older
      adults.

PMID- 17553195
TI  - Eating Well with Canada's Food Guide: "A tool for the times".
AB  - This article outlines the processes undertaken to revise Canada's Food Guide and
      shares the updated science that underpins the dietary pattern. The Dietary
      Reference Intakes provide updated nutrient requirement values and better tools
      for dietary assessment and planning. Alignment with this updated science was an
      important component of defining and communicating accurate dietary guidance for
      Canada. Ensuring that stakeholders had access to the updated review of
      requirements led to the development of the text Dietary Reference Intakes: The
      Essential Guide to Nutrient Requirements. Equally important was ensuring that
      stakeholders were provided opportunity to influence the approach taken to giving
      dietary guidance, both content and the elements of the final package. A
      combination of research, consultation and expert advice guided the process to the
      release of Eating Well with Canada's Food Guide (2007).

PMID- 17553196
TI  - Protein content of pureed diets: implications for planning.
AB  - PURPOSE: Texture-modified diets offered in long-term care (LTC) facilities are
      often prepared from the regular menu, planned using Canada's Food Guide to
      Healthy Eating. The appropriateness of protein levels of pureed diets in LTC
      facilities was determined. METHODS: Protein content was measured in 29 duplicate
      diets, collected from 20 urban LTC facilities in Saskatchewan (SK) and Ontario
      (ON). Mealtime pureed food intakes of 20 LTC residents were assessed. The target
      protein levels were calculated as estimated average requirements plus one or two
      standard deviations of intake, thus allowing for moderate (16%) or low (2.5%)
      risk of inadequacy, respectively. RESULTS: The duplicate diets provided 57.9 +/-
      7.9 and 85.4 +/- 31.1 g/day of protein in SK and ON, respectively. Protein intake
      of SK LTC residents consuming pureed food averaged 54 +/- 19 g/day. Only 43% of
      the SK pureed diets provided more than 59 g/day of protein and none provided more
      than 78 g/day; in contrast, 87% and 40% of ON pureed diets provided more than 59
      and 78 g/day of protein, respectively. CONCLUSIONS: In-house prepared pureed
      diets do not consistently provide sufficient protein levels to ensure a low risk
      of inadequacy for the LTC residents consuming these diets.

PMID- 17553197
TI  - Messages about calcium and weight in Canadian women's magazines.
AB  - PURPOSE: Osteoporosis affects 1.4 million Canadians. Maximizing bone mass by age
      30 may reduce this risk. Because calcium intake and body weight are both
      associated with bone mass, and many Canadian women report that they obtain
      nutrition information from magazines, we compared the frequency of calcium and
      body weight messages in Chatelaine and Flare, Canadian magazines for mature
      versus younger women, respectively. METHODS: Using keywords, we identified
      relevant advertisements and articles in all issues of Chatelaine and Flare for
      2000 to 2001. Data were analyzed using paired t-tests and Wilcoxon signed-rank
      sum tests. RESULTS: Chatelaine had more calcium and weight messages per 100 pages
      than did Flare (significant only for calcium, p <or= 0.0001). Within Chatelaine,
      there were no significant differences between the frequency of calcium and weight
      messages; however, almost 90% of Flare's messages focused on weight (p <or=
      0.0001), with only eight messages in two years addressing calcium. CONCLUSIONS:
      Magazines with limited calcium and many weight messages inadvertently promote a
      lifestyle that may increase the risk for osteoporosis. The opportunity exists to
      provide improved calcium and osteoporosis coverage for women at the prime age for
      maximizing bone density. Awareness of information gaps may help dietitians
      strategize in promoting nutrition messages to women.

PMID- 17553199
TI  - Current treatment strategies in elderly patients with metastatic colorectal
      cancer.
AB  - Colorectal cancer (CRC) is one of the most common cancers in the Western world,
      with > 500,000 new cases diagnosed each year. One of the strongest risk factors
      for colon cancer is age. The incidence rates rise from 10 in 100,000 at age 40-45
      years to 300 in 100,000 at age 75-80 years, with the median age at diagnosis of
      CRC being 71 years. With the general demographic shift toward an aging
      population, the number of people aged > 65 years is expected to increase. This
      article reviews the development of treatment for elderly patients with metastatic
      CRC, from single-agent fluoropyrimidines to combination therapies.

PMID- 17553198
TI  - Supporting healthy eating among preschoolers: challenges for child care staff.
AB  - PURPOSE: The child care setting can help preschoolers develop healthy eating
      habits. Establishing such habits may increase preschoolers' likelihood of
      carrying them into adulthood, which can decrease the risk of nutrition-related
      chronic diseases. Challenges in supporting preschoolers' healthy eating were
      investigated among child care staff. METHODS: Three focus group interviews were
      conducted with 29 child care staff members. Audiotapes of the sessions were
      transcribed. RESULTS: Several themes were identified from the analysis of the
      transcripts. An intrapersonal (individual) factor was children's picky eating.
      Interpersonal factors (interactions) included perceptions that parents do not
      encourage their children to eat in a healthy way, and that child care staff's use
      of practices were inconsistent with health professional recommendations. Physical
      environment factors included perceptions that healthy food was not accessible at
      child care centres and that children have unhealthy food at home. CONCLUSIONS:
      Program planners and health professionals can develop and implement strategies to
      overcome some of the identified challenges to supporting preschoolers' healthy
      eating.

PMID- 17553200
TI  - Phase II trial of oxaliplatin/irinotecan/5-fluorouracil/leucovorin for metastatic
      colorectal cancer.
AB  - BACKGROUND: Individually, oxaliplatin and irinotecan have substantial activity in
      metastatic colorectal cancer (CRC) in combination with 5-fluorouracil/leucovorin.
      A combination regimen using all 4 agents could potentially increase response
      rates in CRC. PATIENTS AND METHODS: A multicenter phase II trial of oxaliplatin
      85 mg/m(2) on day 1, irinotecan 175 mg/m(2) on day 1, 5-fluorouracil 240 mg/m(2)
      by 90-minute infusion on days 2-5, and leucovorin 20 mg/m(2) on days 2-5 of a 21
      day cycle was undertaken in patients with CRC through the North Central Cancer
      Treatment Group. The primary endpoint was response rate, with secondary endpoints
      of toxicity and quality of life. RESULTS: Of 14 patients enrolled (13 evaluable),
      3 partial responses were seen (23%; 95% confidence interval, 5%-54%), and 9
      patients had stable disease (69%). Toxicity was significant, with 1 (8%) grade 5
      event (diarrhea and dehydration) and 3 (23%) grade 4 events (leukopenia and
      diarrhea). The study was closed to further enrollment because of toxicity.
      CONCLUSION: The 4-drug regimen was extremely toxic. Future studies incorporating
      irinotecan- and oxaliplatin-based therapy should consider alternative schedules.

PMID- 17553201
TI  - Phase II study of trabectedin in pretreated patients with advanced colorectal
      cancer.
AB  - PURPOSE: This open-label, nonrandomized, phase II study was aimed at evaluating
      the efficacy and toxicity of trabectedin over a 3-hour intravenous infusion every
      3 weeks in patients with pretreated advanced colorectal cancer. PATIENTS AND
      METHODS: Twenty-one patients were enrolled: 5 patients (23.8%) were treated with
      1650 microg/m(2), 10 patients (47.6%) with 1300 microg/m(2), and 6 patients
      (28.6%) with 1100 microg/m(2). Response to treatment was assessed according to
      World Health Organization criteria, and toxicities were graded according to
      National Cancer Institute Common Toxicity Criteria, version 2.0. RESULTS: The
      median number of treatment cycles per patient was 2 (range, 1-6 cycles). No
      objective responses were reported. Four patients (19%; 95% confidence interval
      [CI], 5.5%-41.9%) exhibited stable disease lasting for a median of 3.6 months
      (range, 2.4-4.9 months). The median time to progression was 1.5 months (95% CI,
      1.3-1.6 months), and the median overall survival was 4.4 months (95% CI, 3-7.5
      months; n=2 censored). The main grade 3/4 toxicities were transient asymptomatic
      transaminase increase (alanine aminotransferase, 66.7% of patients; aspartate
      aminotransferase, 57.1%) and neutropenia (42.8%). No toxic deaths were reported.
      CONCLUSION: Trabectedin 1300 microg/m(2) given as a 3-hour intravenous infusion
      every 3 weeks was well tolerated but lacked activity in pretreated advanced-stage
      colorectal cancer. Therefore, further clinical trials with this trabectedin
      schedule as a single agent are not warranted.

PMID- 17553202
TI  - Treatment with panitumumab after a severe infusion reaction to cetuximab in a
      patient with metastatic colorectal cancer: a case report.
AB  - Monoclonal antibodies targeting the epidermal growth factor receptor (EGFR) are
      effective in the treatment of metastatic colorectal cancer. Cetuximab is a human
      murine chimeric monoclonal antibody targeting the EGFR. Even with premedication,
      cetuximab can result in an infusion reaction in select patients. In a portion of
      these patients, the reaction is severe, and further therapy with cetuximab is
      contraindicated, thus preventing these patients from receiving potentially
      beneficial anti-EGFR therapy. Panitumumab is a fully human monoclonal antibody
      also targeting the EGFR. Panitumumab is given without premedication and, in
      clinical trials, has rarely been associated with infusion reactions. It is not
      yet known whether panitumumab can be safely given in patients with a previous
      severe reaction to cetuximab. We report a case of a patient successfully treated
      with panitumumab after the patient had a severe infusion reaction to cetuximab.

PMID- 17553203
TI  - Primary anorectal malignant melanoma: two case reports and review of the
      literature.
AB  - Anorectal melanoma is a very rare tumor with poor prognosis because of delay in
      diagnosis. It is often mistaken for benign conditions such as hemorrhoids or
      rectal polyps. Surgical treatment ranges from local excision to radical
      abdominoperinal resection. Herein, we report 2 cases of anorectal malignant
      melanoma and further review the diagnostic and therapeutic approaches in light of
      the pertinent literature.

PMID- 17553204
TI  - Revisiting the Cancer and Leukemia Group B/Southwest Oncology Group 80405 Trial:
      a phase III trial of chemotherapy and biologic agents for patients with untreated
      advanced colorectal adenocarcinoma.

PMID- 17553205
TI  - What is standard initial systemic therapy in metastatic renal cell carcinoma?
AB  - Historically, systemic therapies for metastatic renal cell carcinoma RCC) have
      met with minimal success. Recently, an improved understanding of cancer biology
      has been translated into therapies that target pathways critical for RCC growth
      and survival and produce more robust clinical impact. The risks and benefits of
      several approaches to systemic therapy in metastatic RCC are reviewed. The need
      for chronic therapy of novel agents and potential for toxicity raise questions in
      regard to the timing of therapy and value of combination therapy over sequential
      single agents. Further insight into the biology of response, resistance, and
      toxicity is needed to allow for rational patient selection and enhanced
      application of systemic therapies. As new standard therapies for metastatic RCC
      emerge, clinical trial conduct remains a priority to further optimize patient
      outcome.

PMID- 17553206
TI  - The prognostic significance of epidermal growth factor receptor expression in
      clear-cell renal cell carcinoma: a call for standardized methods for
      immunohistochemical evaluation.
AB  - BACKGROUND: Epidermal growth factor receptor (EGFR) is overexpressed in the
      majority of clear-cell renal cell carcinomas (RCCs). The prognostic significance
      of EGFR overexpression after nephrectomy, however, is controversial because of
      different methods used in the immunohistochemical (IHC) evaluation of EGFR
      expression. PATIENTS AND METHODS: In this study, we evaluated EGFR expression and
      its prognostic significance using 3 IHC evaluation methods. A tissue microarray
      composed of 44 cases of clear-cell RCC was stained for the patterns of EGFR
      overexpression, including membranous, cytoplasmic (EGFR-c), and total (membranous
      and cytoplasmic), and the percentage of cells positive for EGFR overexpression
      were recorded. An EGFR composite score was calculated by multiplying the total
      EGFR overexpression score (0-3) and percentage of positive cells. RESULTS:
      Membranous EGFR overexpression was detected in 38 of 44 cases (93.2%), with
      moderate to strong staining (scores 2 and 3) in 35 cases (79.5%). EGFR-c was
      detected in 28 cases (63.6%), with moderate to strong staining (scores 2 and 3)
      in 16 cases (36.4%). EGFR-c was significantly associated with pathologic stage (P
      = 0.003) and Fuhrman nuclear grade (P = 0.042). Epidermal growth factor receptor
      composite score correlated with pathologic stage (P = 0.045) but not Fuhrman
      nuclear grade. However, EGFR expression did not correlate with overall survival
      or disease recurrence. CONCLUSION: This study demonstrates that the prognostic
      value of EGFR overexpression differs significantly when different methods are
      used to evaluate EGFR expression by IHC. Future studies should use standardized
      methods to evaluate the EGFR staining pattern and intensity and the percentage of
      positive cells in order to clarify the prognostic significance of EGFR
      overexpression in clear-cell RCC.

PMID- 17553208
TI  - Weekly docetaxel and bortezomib as first-line treatment for patients with hormone
      refractory prostate cancer: a Minnie Pearl Cancer Research Network phase II
      trial.
AB  - BACKGROUND: Docetaxel is currently the standard first-line treatment in patients
      with hormone-refractory prostate cancer (HRPC). Bortezomib, the first proteasome
      inhibitor in clinical use, demonstrated activity against prostate cancer in phase
      I trials. For this reason, we evaluated the efficacy of docetaxel plus bortezomib
      in the first-line treatment of patients with HRPC. PATIENTS AND METHODS: Between
      February 2004 and May 2005, 63 eligible patients entered this phase II trial. All
      patients had metastatic adenocarcinoma of the prostate that had progressed on
      hormonal therapy. All patients received docetaxel 30 mg/m(2) and bortezomib 1.6
      mg/m(2) on days 1, 8, and 15 of a 28-day cycle. Patients were reevaluated after 8
      weeks of treatment; responding and stable patients continued treatment until
      tumor progression. RESULTS: Sixty patients (95%) received > or = 2 courses of
      treatment and were evaluable for response. Fifteen patients (25%; 95% confidence
      interval, 15%-38%) had a > 50% decrease in serum prostate-specific antigen level
      with treatment; the median response duration was 8 months. The median progression
      free and overall survival times for the entire group were 4.1 months and 13.8
      months, respectively; 20% of patients were alive at 2 years. The regimen was well
      tolerated, with uncommon grade 3/4 toxicity. CONCLUSION: Treatment with this
      combination of weekly docetaxel and bortezomib showed no suggestion of improved
      efficacy versus previous results with docetaxel alone. Bortezomib has minimal
      activity in patients with HRPC and is unlikely to make any impact on treatment
      efficacy.

PMID- 17553207
TI  - The effect of zoledronic acid on bone mineral density in patients undergoing
      androgen deprivation therapy.
AB  - PURPOSE: The aim of this study was to evaluate the efficacy and safety of
      zoledronic acid compared with placebo in preventing bone mineral density (BMD)
      loss and suppressing bone markers when initiated during the first year of
      androgen deprivation therapy in patients with locally advanced prostate cancer.
      PATIENTS AND METHODS: Patients were randomized to receive zoledronic acid 4 mg or
      placebo intravenously every 3 months. Lumbar spine (LS) and total hip BMD was
      measured using dual-energy x-ray absorptiometry at baseline and at week 52. N
      telopeptide (NTX) and bone-specific alkaline phosphatase (BSAP) were evaluated at
      baseline and every 12 weeks. Safety assessments were performed throughout the
      study. RESULTS: Efficacy analyses included 106 patients and 109 patients in the
      zoledronic acid and placebo groups, respectively. At week 52, the least squares
      mean BMD percentage differences were 6.7% for LS and 3.7% for total hip (P <
      0.0001 for both). In the zoledronic acid group, decreases in NTX ((-)14% to (
      )28%) and BSAP ((-)31% to (-)37%) levels were significant and sustained; changes
      in NTX levels and LS BMD (r = (-)0.25; P = 0.04) and in BSAP levels and hip BMD
      (r = (-)0.28; P = 0.02) were significantly correlated. Only traumatic fractures
      were reported for 2 and 3 patients receiving zoledronic acid and placebo,
      respectively. One patient in each group experienced acute renal failure.
      Osteonecrosis of the jaw was not reported. CONCLUSION: Zoledronic acid (4 mg
      intravenously every 3 months) was safe and effective in preventing bone loss and
      reducing bone turnover in patients with prostate cancer when initiated during the
      first year of androgen deprivation therapy; patients with low baseline BMD
      experienced the greatest benefit.

PMID- 17553209
TI  - Anaphylaxis to leuprolide acetate depot injection during treatment for prostate
      cancer.
AB  - A 66-year-old man with clinically localized prostate cancer had elected
      brachytherapy as the primary management of his disease. During induction of
      neoadjuvant androgen deprivation for purposes of cytoreduction, the patient
      experienced anaphylaxis immediately after his first injection of a leuprolide
      acetate depot. He required emergent intubation and extended hospitalization.
      Anaphylactic reactions to leuprolide acetate depots have been described as
      exceedingly rare. To our knowledge, we report the first case of an anaphylactic
      reaction to a leuprolide acetate depot injection in an American man undergoing
      treatment for prostate cancer.

PMID- 17553210
TI  - Spontaneous intraperitoneal perforation of the bladder: a late complication of
      radiation therapy for prostate cancer.
AB  - The spontaneous intraperitoneal rupture of the urinary bladder is an extremely
      rare and life-threatening event. Often, there are difficulties in establishing
      the diagnosis. A patient with spontaneous perforation of the urinary bladder, 17
      years after successful treatment of an adenocarcinoma of the prostate by pelvic
      radiation therapy, is reported. Aspects of etiology, clinical presentation,
      diagnosis, and management are described. Early surgical exploration including
      primary closure of the defect, peritoneal lavage, and continuous vesical drainage
      were associated with a favorable outcome.

PMID- 17553211
TI  - Radiation therapy and sorafenib: clinical data and rationale for the combination
      in metastatic renal cell carcinoma.
AB  - Sorafenib, an inhibitor of multiple tyrosine kinases including vascular
      endothelial growth factor receptor and Raf/mitogen-activated protein kinase,
      increases progression-free survival in metastatic renal cell carcinoma (RCC)
      compared with placebo. The efficacy and toxicity of combined sorafenib and
      radiation therapy (RT) in the treatment of RCC are unknown. This is a
      retrospective report of 3 consecutive patients with metastatic or locally
      recurrent RCC treated with palliative RT while undergoing sorafenib therapy. All
      3 patients experienced disease progression on sorafenib and remained on the drug
      without dose reduction during the RT plus sorafenib regimen. They were followed
      for toxicity and response by clinical history, physical examination, and contrast
      enhanced computed tomography scans. Soon after completion of palliative RT, all 3
      patients experienced complete pain relief without the need for narcotic pain
      medication. Posttreatment imaging revealed partial response with > 50% regression
      of tumor in all patients. None reported significant acute or late side effects at
      follow-up of 3, 6, and 8 months after RT and sorafenib. In the 3 patients with
      recurrent or metastatic RCC in this report, the combination of RT and sorafenib
      was well tolerated and resulted in excellent clinical and radiologic responses.
      This combination is promising and requires further study.

PMID- 17553212
TI  - Beyond behavioural intentions: planning mediates between intentions and physical
      activity.
AB  - OBJECTIVES: Health-behaviour change is not predicted well by behavioural
      intentions alone. Action planning and coping planning are two self-regulatory
      strategies that may help bridge the gap between intentions and behaviour. Action
      planning comprises the when, where and how of implementing a behaviour. Coping
      planning involves the anticipation of barriers and ways to overcome them. The
      study examines whether the inclusion of these two planning constructs would
      improve the overall prediction of physical activity. The main research question
      is which kind of planning would be beneficial for the initiation of behaviour and
      which one for its maintenance. Moreover, it is examined whether intentions
      moderate the planning-behaviour relationship. METHODS: A 5-week longitudinal on
      line study was conducted with 354 participants. Differences in prediction
      patterns between formerly active and formerly inactive individuals were compared
      using multigroup structural equation modelling. Moderating effects of intentions
      were tested by means of latent interactions. RESULTS: Inclusion of the two
      planning factors accounted for substantially more behaviour variance than
      intention alone did. Coping planning mediated the intention-behaviour
      relationship only in formerly active, but not in formerly inactive participants.
      Moreover, intentions moderated the effects of both types of planning on
      behaviour. CONCLUSIONS: Action planning appears to predict behaviour only when
      intentions are high. For actors, coping planning represents a critical self
      regulation strategy to maintain their physical activity levels.

PMID- 17553214
TI  - Loss of heterozygosity analysis in an anaplastic oligodendroglioma arising after
      radiation therapy.
AB  - OBJECTIVE AND IMPORTANCE: Oligodendroglial tumors rarely occur after radiation
      therapy. Here, we report a rare case of anaplastic oligodendroglioma arising
      after radiation therapy, in which genetic analysis was performed. CLINICAL
      PRESENTATION AND INTERVENTION: A 41-year-old man who had received radiation
      therapy for a tumor of the suprasellar and pineal regions 31 years previously,
      presented with headache and progressive right hemiparesis. Magnetic resonance
      (MR) images revealed a ring-enhanced mass lesion in the left frontal lobe. Total
      removal of the tumor was performed through left frontoparietal craniotomy, and
      the histologic diagnosis was anaplastic oligodendroglioma. Using 23
      microsatellite markers, the allelic status of chromosomes 1p, 10, 17p and 19q was
      evaluated by a PCR-based loss of heterozygosity (LOH) assay. Markers on
      chromosomes 1p, 17p and 19q revealed LOH, but none of the markers on chromosome
      10 showed LOH. Based on the genetic analysis, this tumor was considered to be
      sensitive to chemotherapy. Two courses of chemotherapy, with procarbazine, ACNU
      and vincristine, were performed. However, tumor recurrence was detected only 3
      months after the surgery. Despite additional radiochemotherapy, the tumor
      aggressively increased in size and the patient died with multiple recurrent
      tumors 1 year after surgery. CONCLUSION: The anaplastic oligodendroglioma
      presented in this report showed a more aggressive clinical course than was
      expected from the genetic analysis. The significance of 1p and 19q LOH in
      radiation-induced oligodendroglial tumors might differ from that in spontaneous
      counterparts.

PMID- 17553215
TI  - A modeling study of idiopathic intracranial hypertension: etiology and diagnosis.
AB  - OBJECTIVE: To investigate the relationship between idiopathic intracranial
      hypertension (IIH) and transverse sinus stenosis through experiments performed on
      a validated mathematical model. METHODS: A mathematical model of intracranial
      pressure (ICP) dynamics has been extended to accommodate venous sinus compression
      through the introduction of a Starling-like resistor between the sagittal and
      transverse sinuses. RESULTS: In the absence of this type of resistor, the sinuses
      are rigid, and the model has only a unique, stable steady state with normal
      pressures. With resistance a function of the external pressure on the sinus, a
      second stable steady state may exist. This state is characterized by elevated ICP
      concurrent with a compressed transverse sinus. Simulations predict that a
      temporary perturbation that causes a transient elevation of ICP can induce a
      permanent transition from the normal to the higher steady state. Comparisons to
      clinical data from IIH patients provide supporting evidence for the validity of
      the model's predictions. Simulations suggest a possible clinical diagnostic
      technique to determine if an individual has a compressible transverse sinus and
      is at risk for developing IIH. CONCLUSIONS: Results of the model experiments
      suggest that the primary cause of IIH may be a compressible, as opposed to rigid,
      transverse sinus, and that the observed stenosis is a necessary characteristic of
      the elevated pressure state.

PMID- 17553216
TI  - Volume assessment of intracranial large meningiomas and considerations about
      their microsurgical and clinical management.
AB  - OBJECTIVE: To assess the volume of large intracranial meningiomas and analyse
      their different microsurgical and clinical managements. METHOD: The volume of 45
      large meningiomas treated in our department during the last 9.5 years was
      retrospectively assessed using recorded neuronavigation data. The seven most
      employed microsurgical strategies and five important factors influencing the
      patient's outcome (tumor location, grade of peritumoral brain swelling, grade of
      brain atrophy, entrapment of neurovascular structures and the management of the
      vascular infused fluid volume) were individually analysed. The follow-up ranged
      from 14 to 84 months. RESULTS: The assessed volumes exceed 100 cm(3) in 38
      supratentorial and 45 cm(3) in seven infratentorial tumors. The highest averaged
      volume in this series was assessed by tuberculum sellae and olfactory meningiomas
      (174 cc). A complete resection was achieved in 39 patients and was not influenced
      by the tumor volume. However, an averaged volume difference of 60 cc was observed
      between anterior skull base tumors in which their averaged greatest diameter
      variation was only 1.5 cm. Twelve of 24 patients with deep located tumors and
      entrapped neurovascular structures presented accentuated brain swelling. A new
      permanent post-operative neurological deficit was observed only in two patients.
      In the other patients, cranial nerve deficits, pre-operative hemiparesis and
      superior cerebral functions improved to varying degrees. Four cases with subtotal
      resection showed stable residual volumes after 4.5 year follow-up. Three cases
      underwent additional radiosurgery. CONCLUSION: Tumor volume assessment allows an
      improved meningioma size differentiation. Despite the large volume of the tumors
      in this series, satisfactory resection was still possible using single-stage
      procedures. Individual microsurgical strategies and fluids management contributed
      to reducing patient's morbi-mortality.

PMID- 17553217
TI  - Prolonged elevation of magnesium in the cerebrospinal fluid of patients with
      severe head injury.
AB  - OBJECTIVES: Several works have investigated the role of serum magnesium (Mg)
      concentrations in traumatic brain injury. However, there is restricted
      information about cerebrospinal fluid (CSF) levels of Mg in patients with severe
      head injury (SHI). We assessed the changes of Mg concentrations in CSF and serum
      in patients with SHI during the first 10 days after the trauma. METHODS: Eleven
      patients with SHI were studied prospectively on days 1-3, 5 and 10 with analysis
      of CSF and serum levels of Mg and Ca. The control group consisted of nine
      patients with hydrocephalus. RESULTS: CSF levels of Mg were significantly higher
      in patients than controls in the corresponding time points except on days 5 and
      10 of trauma. The CSF Mg levels tended to decrease and the highest level was
      found on day 1 after trauma (2.81 +/- 0.65 mg/dl). In the control group, the CSF
      level of Mg was 1.95 +/- 0.66 mg/dl. No significant difference can be detected
      between controls and patients regarding serum Mg and Ca levels. In addition,
      significantly higher values of Ca in the CSF were observed in all time points
      after trauma in patients with SHI than in the controls. There was no correlation
      between the CSF and serum levels of Mg and Ca levels. DISCUSSION: Our study
      demonstrates that in patients with SHI, CSF levels of Mg and Ca are elevated
      during the whole observation period. Further works should be designed in order to
      show the role and importance of CSF levels of ionized Mg in outcome of patients
      with SHI.

PMID- 17553218
TI  - Economic evaluation and catheter-related bloodstream infections.
AB  - Catheter-related bloodstream infections are a serious problem. Many interventions
      reduce risk, and some have been evaluated in cost-effectiveness studies. We
      review the usefulness and quality of these economic studies. Evidence is
      incomplete, and data required to inform a coherent policy are missing. The cost
      effectiveness studies are characterized by a lack of transparency, short time
      horizons, and narrow economic perspectives. Data quality is low for some
      important model parameters. Authors of future economic evaluations should aim to
      model the complete policy and not just single interventions. They should be
      rigorous in developing the structure of the economic model, include all relevant
      economic outcomes, use a systematic approach for selecting data sources for model
      parameters, and propagate the effect of uncertainty in model parameters on
      conclusions. This will inform future data collection and improve our
      understanding of the economics of preventing these infections.

PMID- 17553219
TI  - Levels of abnormal prion protein in deer and elk with chronic wasting disease.
AB  - Chronic wasting disease (CWD) of deer and elk is a widespread health concern
      because its potential for crossspecies transmission is undetermined. CWD
      prevalence in wild elk is much lower than its prevalence in wild deer, and
      whether CWD-infected deer and elk differ in ability to infect other species is
      unknown. Because lymphoid tissues are important in the pathogenesis of some
      transmissible spongiform encephalopathies such as sheep scrapie, we investigated
      whether CWD-affected elk and deer differ in distribution or quantity of disease
      associated prion protein (PrPres) in lymphoid tissues. Immunoblot quantification
      of PrPres from tonsil and retropharyngeal lymph nodes showed much higher levels
      of PrPres in deer than in elk. This difference correlated with the natural
      prevalence of CWD in these species and suggested that CWD-infected deer may be
      more likely than elk to transmit the disease to other cervids and have a greater
      potential to transmit CWD to noncervids.

PMID- 17553220
TI  - West Nile virus viremia in eastern chipmunks (Tamias striatus) sufficient for
      infecting different mosquitoes.
AB  - In eastern chipmunks (Tamias striatus) inoculated intramuscularly with 101.5 to
      105.7 PFU of West Nile virus (WNV), serum titers developed sufficient to infect
      Aedes triseriatus (Say), Ae. vexans (Meigen), and Culex pipiens (L.). Mean titers
      (95% confidence interval) of 8 chipmunks were 103.9(3.3-4.5), 106.7(6.4-7.0), and
      105.8(4.1-7.5) PFU/mL on days 1-3 postinoculation (p.i.) and 105.8 PFU/mL in 1
      chipmunk on day 4 p.i. Mean estimated days that WNV titers were >104.8 and >105.6
      were 1.7 (1.1-2.3) and 1.4 (1.0-1.6). The longest period of viremia >104.8 PFU/mL
      was 3-4 days. WNV antigen was detected in the small intestine of 2 chipmunks and
      the kidneys of 4 chipmunks by immunohistochemistry. WNV also was detected in
      urine, saliva, and feces of some chipmunks. These data suggest chipmunks might
      play a role in enzootic WNV cycles and be an amplifying host for mosquitoes that
      could infect humans.

PMID- 17553221
TI  - Antimicrobial drug-resistant Escherichia coli from humans and poultry products,
      Minnesota and Wisconsin, 2002-2004.
AB  - The food supply, including poultry products, may transmit antimicrobial drug
      resistant Escherichia coli to humans. To assess this hypothesis, 931
      geographically and temporally matched E. coli isolates from human volunteers
      (hospital inpatients and healthy vegetarians) and commercial poultry products
      (conventionally raised or raised without antimicrobial drugs) were tested by PCR
      for phylogenetic group (A, B1, B2, D) and 60 virulence genes associated with
      extraintestinal pathogenic E. coli. Isolates resistant to trimethoprim
      sulfamethoxazole, quinolones, and extended spectrum cephalosporins (n = 331) were
      compared with drug-susceptible isolates (n = 600) stratified by source.
      Phylogenetic and virulence markers of drug-susceptible human isolates differed
      considerably from those of human and poultry isolates. In contrast, drug
      resistant human isolates were similar to poultry isolates, and drug-susceptible
      and drug-resistant poultry isolates were largely indistinguishable. Many drug
      resistant human fecal E. coli isolates may originate from poultry, whereas drug
      resistant poultry source E. coli isolates likely originate from susceptible
      poultry-source precursors.

PMID- 17553222
TI  - Molecular characteristics and epidemiology of meningococcal carriage, Burkina
      Faso, 2003.
AB  - To describe Neisseria meningitidis strains in the African meningitis belt in
      2003, we obtained 2,389 oropharyngeal swabs at 5 monthly visits a representative
      population sample (age range 4-29 years) in Bobo-Dioulasso, Burkina Faso. A total
      of 152 carriage isolates were grouped, serotyped, and genotyped. Most isolates
      were NG:NT:NST sequence type (ST) 192 (63% of all N. meningitidis), followed by
      W135:2a:P1.5,2 of ST-11 (16%) and NG:15:P1.6 of ST-198 (12%). We also found ST
      2881 (W135:NT:P1.5,2), ST-751 (X:NT:P1.5), and ST-4375 (Y:14:P1.5,2) but not
      serogroups A or C. Estimated average duration of carriage was 30 days (95%
      confidence interval 24-36 days). In the context of endemic group W135 and
      meningococcal A disease, we found substantial diversity in strains carried,
      including all strains currently involved in meningitis in this population, except
      for serogroup A. These findings show the need for large samples and a
      longitudinal design for N. meningitidis serogroup A carriage studies.

PMID- 17553223
TI  - Incidence and cost of rotavirus hospitalizations in Denmark.
AB  - In anticipation of licensure and introduction of rotavirus vaccine into the
      western market, we used modeling of national hospital registry data to determine
      the incidence and direct medical costs of annual rotavirus-associated admissions
      over >11 years in Denmark. Diarrhea-associated hospitalizations coded as
      nonspecified viral or presumed infectious have demonstrated a marked winter peak
      similar to that of rotavirus-associated hospitalizations, which suggests that the
      registered rotavirus-coded admissions are grossly underestimated. We therefore
      obtained more realistic estimates by 2 different models, which indicated 2.4 and
      2.5 (for children <5 years of age) and 4.9 and 5.3 (for children <2 years of age)
      rotavirus-associated admissions per 1,000 children per year, respectively. These
      admissions amount to associated direct medical costs of US $1.7-1.8 million per
      year. Using 2 simple models to analyze readily available hospital discharge data
      resulted in more consistent and reliable estimates.

PMID- 17553224
TI  - Strategies to reduce person-to-person transmission during widespread Escherichia
      coli O157:H7 outbreak.
AB  - During the Escherichia coli O157:H7 outbreak in 2006 in the United States, the
      primary strategy to prevent illness was to advise consumers not to eat spinach.
      No widespread warnings were issued about preventing person-to-person (secondary)
      transmission. A disease transmission model, fitted to the current data, was used
      to investigate likely reductions in illnesses that could result from
      interventions to prevent secondary transmission. The model indicates that
      exposure to contaminated spinach occurred early in the outbreak and that
      secondary transmission was similar to that in previous E. coli outbreaks ( 12%).
      The model also suggests that even a modestly effective strategy to interrupt
      secondary transmission (prevention of only 2%-3% of secondary illnesses) could
      result in a reduction of 5%-11% of symptomatic cases. This analysis supports the
      use of widespread public health messages during outbreaks of E. coli O157:H7 with
      specific advice on how to interrupt secondary transmission.

PMID- 17553225
TI  - Bovine spongiform encephalopathy and spatial analysis of the feed industry.
AB  - In France, despite the ban of meat-and-bone meal (MBM) in cattle feed, bovine
      spongiform encephalopathy (BSE) was detected in hundreds of cattle born after the
      ban. To study the role of MBM, animal fat, and dicalcium phosphate on the risk
      for BSE after the feed ban, we conducted a spatial analysis of the feed industry.
      We used data from 629 BSE cases as well as data on use of each byproduct and
      market area of the feed factories. We mapped risk for BSE in 951 areas supplied
      by the same factories and connection with use of byproducts. A disease map of BSE
      with covariates was built with the hierarchical Bayesian modeling methods, based
      on Poisson distribution with spatial smoothing. Only use of MBM was spatially
      linked to risk for BSE, which highlights cross-contamination as the most probable
      source of infection after the feed ban.

PMID- 17553226
TI  - Minority-variant pfcrt K76T mutations and chloroquine resistance, Malawi.
AB  - Genotyping of the chloroquine-resistance biomarker pfcrt (Plasmodium falciparum
      chloroquine resistance transporter gene) suggests that, in the absence of
      chloroquine pressure, Plasmodium falciparum parasites in Malawi have reverted to
      chloroquine sensitivity. However, malaria infections in Africa are commonly
      polyclonal, and standard PCRs cannot detect minority genotypes if present in <20%
      of the parasites in an individual host. We have developed a multiple site
      specific heteroduplex tracking assay (MSS-HTA) that can detect pfcrt 76T mutant
      parasites consisting of as little as 1% of the parasite population. In clinical
      samples, no pfcrt 76T was detected in 87 pregnant Malawian women by standard PCR.
      However, 22 (25%) contained minority-variant resistant genotypes detected by the
      MSS-HTA. These results were confirmed by subcloning and sequencing. This finding
      suggests that the chloroquine-resistant genotype remains common in Malawians and
      that PCR-undetectable drug-resistant genotypes may be present in disease-endemic
      populations. Surveillance for minority-variant drug resistant mutations may be
      useful in making antimalarial drug policy.

PMID- 17553227
TI  - Human alveolar echinococcosis after fox population increase, Switzerland.
AB  - We analyzed databases spanning 50 years, which included retrospective alveolar
      echinococcosis (AE) case finding studies and databases of the 3 major centers for
      treatment of AE in Switzerland. A total of 494 cases were recorded. Annual
      incidence of AE per 100,000 population increased from 0.12-0.15 during 1956-1992
      and a mean of 0.10 during 1993-2000 to a mean of 0.26 during 2001-2005. Because
      the clinical stage of the disease did not change between observation periods,
      this increase cannot be explained by improved diagnosis. Swiss hunting statistics
      suggested that the fox population increased 4-fold from 1980 through 1995 and has
      persisted at these higher levels. Because the period between infection and
      development of clinical disease is long, the increase in the fox population and
      high Echinococcus multilocularis prevalence rates in foxes in rural and urban
      areas may have resulted in an emerging epidemic of AE 10-15 years later.

PMID- 17553228
TI  - Risk factors for imported fatal Plasmodium falciparum malaria, France, 1996-2003.
AB  - Plasmodium falciparum malaria is a serious health hazard for travelers to malaria
      endemic areas and is often diagnosed on return to the country of residence. We
      conducted a retrospective study of imported falciparum malaria among travelers
      returning to France from malaria-endemic areas from 1996 through 2003.
      Epidemiologic, clinical, and parasitologic data were collected by a network of
      120 laboratories. Factors associated with fatal malaria were identified by
      logistic regression analysis. During the study period, 21,888 falciparum malaria
      cases were reported. There were 96 deaths, for a case-fatality rate of 4.4 per
      1,000 cases of falciparum malaria. In multivariate analysis, risk factors
      independently associated with death from imported malaria were older age,
      European origin, travel to East Africa, and absence of chemoprophylaxis. Fatal
      imported malaria remains rare and preventable. Pretravel advice and malaria
      management should take into account these risk factors, particularly for senior
      travelers.

PMID- 17553229
TI  - Isolation and characterization of novel human parechovirus from clinical samples.
AB  - Using Vero cells, we isolated a virus (NII561-2000) from a cerebrospinal fluid
      specimen of a 1-year-old girl with Reye syndrome. The determined amino acid
      sequence of the virus indicated that the isolate was a human parechovirus (HPeV),
      a member of Picornaviridae. Neutralization test showed that the NII561-2000 virus
      had distinct antigenicity to HPeV-1, HPeV-2, and HPeV-3, and that the sequence
      was distinct from these types as well as from HPeV-4 and HPeV-5. Thus, we propose
      the virus (NII561-2000) as the prototype of HPeV-6. We isolated 10 NII561-2000
      related viruses, 14 HPeV-1, 16 HPeV-3, and 1 HPeV-4 of 41 HPeVs from various
      clinical samples collected in Niigata, Japan. Clinical symptoms of the persons
      infected with the NII561-2000-related viruses were infectious gastroenteritis,
      rash, upper respiratory tract infection, and paralysis, in addition to Reye
      syndrome in the 1-year-old girl.

PMID- 17553230
TI  - Melioidosis outbreak after typhoon, southern Taiwan.
AB  - From July through September 2005, shortly after a typhoon, 40 cases of
      Burkholderia pseudomallei infection (melioidosis) were identified in southern
      Taiwan. Two genotypes that had been present in 2000 were identified by pulsed
      field gel electrophoresis. Such a case cluster confirms that melioidosis is
      endemic to Taiwan.

PMID- 17553231
TI  - Loop-mediated isothermal amplification for influenza A (H5N1) virus.
AB  - We describe a 1-step reverse-transcription loop-mediated isothermal amplification
      assay for detection of highly pathogenic avian influenza A (H5N1) viruses. The
      assay was tested by using a panel of highly pathogenic H5N1 subtypes isolated
      over the past 10 years and clinical specimens. The assay produced negative
      results for all non-H5N1 subtypes.

PMID- 17553232
TI  - Nosocomial buffalopoxvirus infection, Karachi, Pakistan.
AB  - During 5 months in 2004-2005, buffalopoxvirus infection, confirmed by virus
      isolation and limited nucleic acid sequencing, spread between 5 burns units in
      Karachi, Pakistan. The outbreak was related to movement of patients between
      units. Control measures reduced transmission, but sporadic cases continued due to
      the admission of new patients with community-acquired infections.

PMID- 17553233
TI  - Tickborne encephalitis in naturally exposed monkey (Macaca sylvanus).
AB  - We describe tickborne encephalitis (TBE) in a monkey (Macaca sylvanus) after
      natural exposure in an area at risk for TBE. TBE virus was present in the brain
      and could be identified as closely related to the European subtype, strain
      Neudoerfl.

PMID- 17553234
TI  - Norovirus infection in children with acute gastroenteritis, Madagascar, 2004
      2005.
AB  - Of 237 children with acute gastroenteritis in Antananarivo, Madagascar, during
      May 2004-May 2005, 14 ( 6%) were infected with norovirus. Seasonality (November
      December peak) was detected. Reverse transcription-PCR identified GII as the most
      common genogroup. GIs belonged to GI.1, GI.3, and GI.4. Noroviruses in Madagascar
      show extensive genetic diversity.

PMID- 17553235
TI  - Reemergence of Oropouche fever, northern Brazil.
AB  - Oropouche fever has reemerged in Parauapebas and Porto de Moz municipalities,
      Para State, Brazil. Serologic analysis (immunoglobulin M-ELISA) and virus
      isolation confirmed Oropouche virus (OROV) in both municipalities. Nucleotide
      sequencing of 2 OROV isolates from each location indicated genotypes I
      (Parauapebas) and II (Porto de Moz) in Brazil.

PMID- 17553236
TI  - Emergence of serotype G12 rotaviruses, Hungary.
AB  - We describe the emergence of serotype G12 rotaviruses (67 [6.9%] of 971 specimens
      tested) among children hospitalized with rotavirus gastroenteritis in Hungary
      during 2005. These findings are consistent with recent reports of the possible
      global spread and increasing epidemiologic importance of these strains, which may
      have implications for current rotavirus vaccination strategies.

PMID- 17553237
TI  - Meningitis serogroup W135 outbreak, Burkina Faso, 2002.
AB  - In 2002, the largest epidemic of Neisseria meningitidis serogroup W135 occurred
      in Burkina Faso. The highest attack rate was in children <5 years of age. We
      describe cases from 1 district and evaluate the performance of the Pastorex test,
      which had good sensitivity (84%) and specificity (89%) compared with culture or
      PCR.

PMID- 17553238
TI  - Age and clinical dengue illness.
AB  - The relationship between age and risk for classic dengue fever has never been
      quantified. We use data from clinical patients to show that the relative risk of
      having classical disease after primary dengue virus infection increases with age.
      This relationship has implications for strategies aimed at controlling dengue
      fever.

PMID- 17553239
TI  - Murine typhus in children, South Texas.
AB  - Children from South Texas were evaluated for immunoglobulin G to Rickettsia
      typhi, the causative agent of murine typhus. Of 513 children, 8.6% of those 1-5
      years of age, 13.3% of those 6-11 years of age, and 13.8% of those 12-17 years of
      age had positive results.

PMID- 17553240
TI  - Full recovery from Baylisascaris procyonis eosinophilic meningitis.
AB  - Infection by Baylisascaris procyonis is an uncommon but devastating cause of
      eosinophilic meningitis. We report the first case-patient, to our knowledge, who
      recovered from B. procyonis eosinophilic meningitis without any recognizable
      neurologic deficits. The spectrum of illness for this organism may be wider than
      previously recognized.

PMID- 17553241
TI  - Plasmodium malariae in Haitian refugees, Jamaica.
AB  - Since 1963, reported malaria transmission in Haiti has been restricted to
      Plasmodium falciparum. However, screening of Haitian refugees in Jamaica in 2004,
      by microscopic examination, identified P. falciparum, P. vivax, and P. malariae.
      PCR confirmed the P. malariae and P. falciparum but not P. vivax infections. DNA
      sequencing and rRNA gene sequences showed transmission of P. malariae. This
      report confirms that P. malariae is still being transmitted in Haiti.

PMID- 17553242
TI  - Endemic human monkeypox, Democratic Republic of Congo, 2001-2004.
AB  - By analyzing vesicle fluids and crusted scabs from 136 persons with suspected
      monkeypox, we identified 51 cases of monkeypox by PCR, sequenced the
      hemagglutinin gene, and confirmed 94% of cases by virus culture. PCR demonstrated
      chickenpox in 61 patients. Coinfection with both viruses was found in 1
      additional patient.

PMID- 17553243
TI  - Bartonella species in blood of immunocompetent persons with animal and arthropod
      contact.
AB  - Using PCR in conjunction with pre-enrichment culture, we detected Bartonella
      henselae and B. vinsonii subspecies berkhoffii in the blood of 14 immunocompetent
      persons who had frequent animal contact and arthropod exposure.

PMID- 17553244
TI  - Response to malaria epidemics in Africa.
AB  - Malaria epidemics affect nonimmune populations in many highland and semi-arid
      areas of Africa. Effective prevention of these epidemics is challenging,
      particularly in the highlands where predictive accuracy of indicators is not
      sufficiently high to allow decisions involving expensive measures such as indoor
      residual spraying of insecticides. Advances in geographic information systems
      have proved useful in stratification of areas to guide selective targeting of
      interventions, including barrier application of insecticides in transmission foci
      to prevent spread of infection. Because rainfall is associated with epidemics in
      semi-arid areas, early warning methods based on seasonal climate predictions have
      been proposed. For most areas, response measures should focus on early
      recognition of anomalies and rapid mass drug administration. Vector control
      measures are useful if abnormal transmission is highly likely and if they can be
      selectively implemented at the early stages of an outbreak.

PMID- 17553245
TI  - Plague and the human flea, Tanzania.
AB  - Domestic fleas were collected in 12 villages in the western Usambara Mountains in
      Tanzania. Of these, 7 are considered villages with high plague frequency, where
      human plague was recorded during at least 6 of the 17 plague seasons between 1986
      and 2004. In the remaining 5 villages with low plague frequency, plague was
      either rare or unrecorded. Pulex irritans, known as the human flea, was the
      predominant flea species (72.4%) in houses. The density of P. irritans, but not
      of other domestic fleas, was significantly higher in villages with a higher
      plague frequency or incidence. Moreover, the P. irritans index was strongly
      positively correlated with plague frequency and with the logarithmically
      transformed plague incidence. These observations suggest that in Lushoto District
      human fleas may play a role in plague epidemiology. These findings are of
      immediate public health relevance because they provide an indicator that can be
      surveyed to assess the risk for plague.

PMID- 17553246
TI  - Trends for influenza-related deaths during pandemic and epidemic seasons, Italy,
      1969-2001.
AB  - Age-specific patterns of death from influenza vary, depending on whether the
      influenza season is epidemic or pandemic. We assessed age patterns and geographic
      trends in monthly influenza-related deaths in Italy from 1969 through 2001,
      focusing on differences between epidemic and pandemic seasons. We evaluated age
      standardized excess deaths from pneumonia and influenza and from all causes,
      using a modified version of a cyclical Serfling model. Excess deaths were highest
      for elderly persons in all seasons except the influenza A (H3N2) pandemic season
      (1969-70), when rates were greater for younger persons, confirming a shift toward
      death of younger persons during pandemic seasons. When comparing northern,
      central, and southern Italy, we found a high level of synchrony in the amplitude
      of peaks of influenza-related deaths.

PMID- 17553247
TI  - Respirator donning in post-hurricane New Orleans.
AB  - We evaluated correctness of N95 filtering facepiece respirator donning by the
      public in post-hurricane New Orleans, where respirators were recommended for mold
      remediation. We randomly selected, interviewed, and observed 538 participants,
      using multiple logistic regression for analysis. Only 129 (24%) participants
      demonstrated proper donning. Errors included nose clip not tightened (71%) and
      straps incorrectly placed (52%); 22% put on the respirator upside down. Factors
      independently associated with proper donning were as follows: ever having used a
      mask or respirator (odds ratio [OR] 5.28; 95% confidence interval [CI], 1.79
      22.64); ever having had a respirator fit test (OR 4.40; 95% CI, 2.52-7.81); being
      male (OR 2.44; 95% CI, 1.50-4.03); Caucasian race (OR 2.09; 95% CI, 1.32-3.33);
      having a certified respirator (OR 1.99, 95% CI, 1.20-3.28); and having
      participated in mold clean-up (OR 1.82; 95% CI,1.00-3.41). Interventions to
      improve respirator donning should be considered in planning for influenza
      epidemics and disasters.

PMID- 17553248
TI  - Apoptosis and pathogenesis of avian influenza A (H5N1) virus in humans.
AB  - The pathogenesis of avian influenza A (H5N1) virus in humans has not been clearly
      elucidated. Apoptosis may also play an important role. We studied autopsy
      specimens from 2 patients who died of infection with this virus. Apoptosis was
      observed in alveolar epithelial cells, which is the major target cell type for
      the viral replication. Numerous apoptotic leukocytes were observed in the lung of
      a patient who died on day 6 of illness. Our data suggest that apoptosis may play
      a major role in the pathogenesis of influenza (H5N1) virus in humans by
      destroying alveolar epithelial cells. This pathogenesis causes pneumonia and
      destroys leukocytes, leading to leukopenia, which is a prominent clinical feature
      of influenza (H5N1) virus in humans. Whether observed apoptotic cells were a
      direct result of the viral replication or a consequence of an overactivation of
      the immune system requires further studies.

PMID- 17553249
TI  - Genome analysis linking recent European and African influenza (H5N1) viruses.
AB  - To better understand the ecology and epidemiology of the highly pathogenic avian
      influenza virus in its transcontinental spread, we sequenced and analyzed the
      complete genomes of 36 recent influenza A (H5N1) viruses collected from birds in
      Europe, northern Africa, and southeastern Asia. These sequences, among the first
      complete genomes of influenza (H5N1) viruses outside Asia, clearly depict the
      lineages now infecting wild and domestic birds in Europe and Africa and show the
      relationships among these isolates and other strains affecting both birds and
      humans. The isolates fall into 3 distinct lineages, 1 of which contains all known
      non-Asian isolates. This new Euro-African lineage, which was the cause of several
      recent (2006) fatal human infections in Egypt and Iraq, has been introduced at
      least 3 times into the European-African region and has split into 3 distinct,
      independently evolving sublineages. One isolate provides evidence that 2 of these
      sublineages have recently reassorted.

PMID- 17553250
TI  - Pet rodents and fatal lymphocytic choriomeningitis in transplant patients.
AB  - In April 2005, 4 transplant recipients became ill after receiving organs infected
      with lymphocytic choriomeningitis virus (LCMV); 3 subsequently died. All organs
      came from a donor who had been exposed to a hamster infected with LCMV. The
      hamster was traced back through a Rhode Island pet store to a distribution center
      in Ohio, and more LCMV-infected hamsters were discovered in both. Rodents from
      the Ohio facility and its parent facility in Arkansas were tested for the same
      LCMV strain as the 1 involved in the transplant-associated deaths. Phylogenetic
      analysis of virus sequences linked the rodents from the Ohio facility to the
      Rhode Island pet store, the index hamster, and the transplant recipients. This
      report details the animal traceback and the supporting laboratory investigations.

PMID- 17553251
TI  - International spread of multidrug-resistant Salmonella Schwarzengrund in food
      products.
AB  - We compared 581 Salmonella enterica serotype Schwarzengrund isolates from
      persons, food, and food animals in Denmark, Thailand, and the United States by
      antimicrobial drug susceptibility and pulsed-field gel electrophoresis (PFGE)
      typing. Resistance, including resistance to nalidixic acid, was frequent among
      isolates from persons and chickens in Thailand, persons in the United States, and
      food imported from Thailand to Denmark and the United States. A total of 183 PFGE
      patterns were observed, and 136 (23.4%) isolates had the 3 most common patterns.
      Seven of 14 isolates from persons in Denmark had patterns found in persons and
      chicken meat in Thailand; 22 of 390 human isolates from the United States had
      patterns found in Denmark and Thailand. This study suggests spread of multidrug
      resistant S. Schwarzengrund from chickens to persons in Thailand, and from
      imported Thai food products to persons in Denmark and the United States.

PMID- 17553252
TI  - Rudolf Virchow and the recognition of alveolar echinococcosis, 1850s.
AB  - Alveolar echinococcosis, which is caused by the larval stage of the fox tapeworm
      Echinococcus multilocularis, is one of the most dangerous parasitic diseases. It
      is endemic in many parts of the Northern Hemisphere and an emerging health
      problem in the People's Republic of China. In Europe and North America, human
      cases are rare, but concomitant with an increase in the population of the final
      host, the red fox, an increase of human infections is expected. Rudolf Virchow,
      the father of the concept of cellular pathology, determined in the 1850s that an
      Echinococcus sp. was the causative agent of this enigmatic emerging disease. In
      his famous publication in 1855, he described the clinical course of the disease,
      its macroscopic aspects, and histopathologic findings in detail. He also
      identified the disease formerly known as alveolar colloid of the liver to be an
      infection with the larval stage of an Echinococcus sp.

PMID- 17553253
TI  - Fatal disseminated Acanthamoeba lenticulata infection in a heart transplant
      patient.
AB  - We report a fatal case of disseminated acanthamebiasis caused by Acanthamoeba
      lenticulata (genotype T5) in a 39-year-old heart transplant recipient. The
      diagnosis was based on skin histopathologic results and confirmed by isolation of
      the ameba from involved skin and molecular analysis of a partial 18S rRNA gene
      sequence (DF3).

PMID- 17553254
TI  - Leptospirosis in urban wild boars, Berlin, Germany.
AB  - We found antibodies to leptospires in 25 (18%) of 141 wild boars from Berlin (95%
      confidence interval 12-25). Seropositivity was associated with chronic
      interstitial nephritis (odds ratio 10.5; p=0.01), and leptospires were detected
      in kidney tissues. Wild boars represent a potential source for human
      leptospirosis in urban environments.

PMID- 17553255
TI  - Mycobacterium liflandii infection in European colony of Silurana tropicalis.
AB  - Mycobacterium liflandii causes a fatal frog disease in captive anurans. Here we
      report, to our knowledge, the first epizootic of mycobacteriosis in a European
      colony of clawed frogs (Silurana tropicalis), previously imported from a United
      States biologic supply company. Our findings suggest the emerging potential of
      this infection through international trade.

PMID- 17553256
TI  - Environmental source of Candida dubliniensis.
AB  - We isolated Candida dubliniensis from a nonhuman source, namely, tick samples
      from an Irish seabird colony. The species was unambiguously identifi ed by
      phenotypic and genotypic means. Analysis of the 5.8S rRNA gene showed that the
      environmental isolates belong to C. dubliniensis genotype 1.

PMID- 17553257
TI  - Gulf Coast ticks (Amblyomma maculatum) and Rickettsia parkeri, United States.
AB  - Geographic distribution of Rickettsia parkeri in its US tick vector, Amblyomma
      maculatum, was evaluated by PCR. R. parkeri was detected in ticks from Florida,
      Georgia, Kentucky, Mississippi, Oklahoma, and South Carolina, which suggests that
      A. maculatum may be responsible for additional cases of R. parkeri rickettsiosis
      throughout much of its US range.

PMID- 17553258
TI  - Outbreak of Yersinia enterocolitica serogroup O:9 infection and processed pork,
      Norway.
AB  - An outbreak involving 11 persons infected with Yersinia enterocolitica O:9 was
      investigated in Norway in February 2006. A case-control study and microbiologic
      investigation indicated a ready-to-eat pork product as the probable source.
      Appropriate control measures are needed to address consumer risk associated with
      this product.

PMID- 17553259
TI  - Enteroaggregative Escherichia coli related to uropathogenic clonal group A.
AB  - Enteroaggregative Escherichia coli (EAEC) are heterogeneous, diarrheagenic E.
      coli. Of EAEC strains from Nigeria, 10 independent antimicrobial-resistant
      isolates belonged to the multilocus sequence type 69 clonal complex, to which
      uropathogenic E. coli clonal group A belongs. This finding suggests a recent
      common ancestor for these distinct groups of pathogenic E. coli.

PMID- 17553260
TI  - Antimicrobial drugs and community-acquired Clostridium difficile-associated
      disease, UK.
AB  - In a population-based case-control study of community acquired Clostridium
      difficile-associated disease (CDAD), we matched 1,233 cases to 12,330 controls.
      CDAD risk increased 3-fold with use of any antimicrobial agent and 6-fold with
      use of fluoroquinolones. Prior use of antimicrobial agents did not affect risk
      for CDAD after 6 months.

PMID- 17553261
TI  - Chikungunya virus in US travelers returning from India, 2006.
AB  - Chikungunya virus (CHIKV), a mosquito-borne alphavirus, is endemic in Africa and
      Asia. In 2005-2006, CHIKV epidemics were reported in islands in the Indian Ocean
      and in southern India. We present data on laboratory-confirmed CHIKV infections
      among travelers returning from India to the United States during 2006.

PMID- 17553262
TI  - Chikungunya virus, Cameroon, 2006.
AB  - We report the isolation of chikungunya virus from a patient during an outbreak of
      a denguelike syndrome in Cameroon in 2006. The virus was phylogenetically grouped
      in the Democratic Republic of the Congo cluster, indicating a continuous
      circulation of a genetically similar chikungunya virus population during 6 years
      in Central Africa.

PMID- 17553263
TI  - Avian influenza (H5N1) virus in waterfowl and chickens, central China.
AB  - In 2004, 3 and 4 strains of avian influenza virus (subtype H5N1) were isolated
      from waterfowl and chickens, respectively, in central People's Republic of China.
      Viral replication and pathogenicity were evaluated in chickens, quails, pigeons,
      and mice. We analyzed the sequences of the hemagglutinin and neuraminidase genes
      of the isolates and found broad diversity among them.

PMID- 17553264
TI  - Tuberculosis drug resistance and HIV infection, the Netherlands.
AB  - In the Netherlands during 1993-2001, multidrug-resistant tuberculosis among newly
      diagnosed patients was more frequent in those with HIV coinfection (5/308, 1.6%)
      than in those with no HIV infection (39/646, 0.6%; adjusted odds ratio 3.43,
      p=0.015). Four of the 5 patients coinfected with multidrug-resistant tuberculosis
      and HIV were foreign-born. DNA fingerprint analysis suggested that transmission
      had occurred outside the Netherlands.

PMID- 17553265
TI  - Human benefits of animal interventions for zoonosis control.
AB  - Although industrialized countries have been able to contain recent outbreaks of
      zoonotic diseases, many resource-limited and transitioning countries have not
      been able to react adequately. The key for controlling zoonoses such as rabies,
      echinococcosis, and brucellosis is to focus on the animal reservoir. In this
      respect, ministries of health question whether the public health sector really
      benefits from interventions for livestock. Cross-sectoral assessments of
      interventions such as mass vaccination for brucellosis in Mongolia or vaccination
      of dogs for rabies in Chad consider human and animal health sectors from a
      societal economic perspective. Combining the total societal benefits, the
      intervention in the animal sector saves money and provides the economic argument,
      which opens new approaches for the control of zoonoses in resource-limited
      countries through contributions from multiple sectors.

PMID- 17553266
TI  - Hantavirus and arenavirus antibodies in persons with occupational rodent
      exposure.
AB  - Rodents are the principal hosts of Sin Nombre virus, 4 other hantaviruses known
      to cause hantavirus pulmonary syndrome in North America, and the 3 North American
      arenaviruses. Serum samples from 757 persons who had worked with rodents in North
      America and handled neotomine or sigmodontine rodents were tested for antibodies
      against Sin Nombre virus, Whitewater Arroyo virus, Guanarito virus, and
      lymphocytic choriomeningitis virus. Antibodies against Sin Nombre virus were
      found in 4 persons, against Whitewater Arroyo virus or Guanarito virus in 2
      persons, and against lymphocytic choriomeningitis virus in none. These results
      suggest that risk for infection with hantaviruses or arenaviruses usually is low
      in persons whose occupations entail close physical contact with neotomine or
      sigmodontine rodents in North America.

PMID- 17553267
TI  - Influenza (H5N1) viruses in poultry, Russian Federation, 2005-2006.
AB  - We studied 7 influenza (H5N1) viruses isolated from poultry in western Siberia
      and the European part of the Russian Federation during July 2005-February 2006.
      Full genome sequences showed high homology to Qinghai-like influenza (H5N1)
      viruses. Phylogenetic analysis not only showed a close genetic relationship
      between the H5N1 strains isolated from poultry and wild migratory waterfowls but
      also suggested genetic reassortment among the analyzed isolates. Analysis of
      deduced amino acid sequences of the M2 and neuraminidase proteins showed that all
      isolates are potentially sensitive to currently available antiviral drugs.
      Pathogenicity testing showed that all studied viruses were highly pathogenic in
      chickens; for 3 isolates tested in mice and 2 tested in ferrets, pathogenicity
      was heterogeneous. Pathogenicity in mammalian models was generally correlated
      with Lys at residue 627 of polymerase basic protein 2.

PMID- 17553268
TI  - Movements of birds and avian influenza from Asia into Alaska.
AB  - Asian-origin avian influenza (AI) viruses are spread in part by migratory birds.
      In Alaska, diverse avian hosts from Asia and the Americas overlap in a region of
      intercontinental avifaunal mixing. This region is hypothesized to be a zone of
      Asia-to-America virus transfer because birds there can mingle in waters
      contaminated by wild-bird-origin AI viruses. Our 7 years of AI virus surveillance
      among waterfowl and shorebirds in this region (1998-2004; 8,254 samples) showed
      remarkably low infection rates (0.06%). Our findings suggest an Arctic effect on
      viral ecology, caused perhaps by low ecosystem productivity and low host
      densities relative to available water. Combined with a synthesis of avian
      diversity and abundance, intercontinental host movements, and genetic analyses,
      our results suggest that the risk and probably the frequency of intercontinental
      virus transfer in this region are relatively low.

PMID- 17553269
TI  - Diagnosis of tuberculosis by an enzyme-linked immunospot assay for interferon
      gamma.
AB  - We evaluated an enzyme-linked immunospot assay for interferon-gamma (T SPOT-TB)
      for rapid diagnosis of active tuberculosis (TB) in a disease-endemic area. From
      January to June 2005, patients whose clinical symptoms and radiographic findings
      were compatible with TB were recruited, and a blood sample was obtained for T
      SPOT-TB assay within 7 days of microbiologic studies. Sixty-five patients were
      studied, including 39 (60%) with active TB. Thirty-five (53.8%) patients had
      underlying medical conditions. Thirty-seven patients had positive cultures for
      Mycobacterium tuberculosis, and 11 patients had positive cultures for
      nontuberculous mycobacteria. The sensitivity, specificity, positive predictive
      value, and negative predictive value of the T SPOT-TB assay were 87.2%, 88.5%,
      91.9%, and 82.1%, respectively. The accuracy of this test in diagnosing active TB
      is >80%, even in an area with a high incidence of nontuberculous mycobacterial
      disease.

PMID- 17553270
TI  - Global emergence of trimethoprim/sulfamethoxazole resistance in Stenotrophomonas
      maltophilia mediated by acquisition of sul genes.
AB  - Trimethoprim/sulfamethoxazole (TMP/SMX) resistance remains a serious threat in
      the treatment of Stenotrophomonas maltophilia infections. We analyzed an
      international collection of 55 S. maltophilia TMP/SMX-sensitive (S) (n=30) and 
      resistant (R) (n=25) strains for integrons; sul1, sul2 and dhfr genes; and
      insertion element common region (ISCR) elements. sul1, as part of a class 1
      integron, was detected in 17 of 25 TMP/SMX-R. Nine TMP/SMX-R strains carried
      sul2; 7 were on large plasmids. Five TMP/SMX-R isolates were positive for ISCR2,
      and 4 were linked to sul2; 2 others possessed ISCR3. Two ISCR2s were adjacent to
      floR. Six TMP/SMX-S isolates harbored novel ISCR elements, ISCR9 and ISCR10.
      Linkage of ISCR3, ISCR9, and ISCR10 to sul2 and dhfr genes was not demonstrated.
      The data from this study indicate that class 1 integrons and ISCR elements linked
      to sul2 genes can mediate TMP/SMX resistance in S. maltophilia and are
      geographically widespread, findings that reinforce the need for ongoing
      resistance surveillance.

PMID- 17553271
TI  - Flinders Island spotted fever rickettsioses caused by "marmionii" strain of
      Rickettsia honei, Eastern Australia.
AB  - Australia has 4 rickettsial diseases: murine typhus, Queensland tick typhus,
      Flinders Island spotted fever, and scrub typhus. We describe 7 cases of a
      rickettsiosis with an acute onset and symptoms of fever (100%), headache (71%),
      arthralgia (43%), myalgia (43%), cough (43%), maculopapular/petechial rash (43%),
      nausea (29%), pharyngitis (29%), lymphadenopathy (29%), and eschar (29%). Cases
      were most prevalent in autumn and from eastern Australia, including Queensland,
      Tasmania, and South Australia. One patient had a history of tick bite
      (Haemaphysalis novaeguineae). An isolate shared 99.2%, 99.8%, 99.8%, 99.9%, and
      100% homology with the 17 kDa, ompA, gltA, 16S rRNA, and Sca4 genes,
      respectively, of Rickettsia honei. This Australian rickettsiosis has similar
      symptoms to Flinders Island spotted fever, and the strain is genetically related
      to R. honei. It has been designated the "marmionii" strain of R. honei, in honor
      of Australian physician and scientist Barrie Marmion.

PMID- 17553272
TI  - Symptomatic and subclinical infection with rotavirus P[8]G9, rural Ecuador.
AB  - During the past decade, rotavirus genotype G9 has spread throughout the world,
      adding to and sometimes supplanting the common genotypes G1-G4. We report
      evidence of this spread in a population sample within rural Ecuador. A total of
      1,656 stool samples were collected from both patients with diarrhea and from
      asymptomatic residents in 22 remote communities in northwestern Ecuador from
      August 2003 through February 2006. Rotavirus was detected in 23.4% of case
      patients and 3.2% of controls. From these 136 rotavirus-positive samples, a
      subset of 47 were genotyped; 72% were of genotype G9, and 62% were genotype
      P[8]G9. As a comparison, 29 rotavirus-positive stool samples were collected from
      a hospital in Quito during March 2006 and genotyped; 86% were of genotype P[8]G9.
      Few countries have reported P[8]G9 rotavirus detection rates as high as those of
      the current study. This growing prevalence may require changes to current
      vaccination programs to include coverage for this genotype.

PMID- 17553273
TI  - Effectiveness of interventions to reduce contact rates during a simulated
      influenza pandemic.
AB  - Measures to decrease contact between persons during an influenza pandemic have
      been included in pandemic response plans. We used stochastic simulation models to
      explore the effects of school closings, voluntary confinements of ill persons and
      their household contacts, and reductions in contacts among long-term care
      facility (LTCF) residents on pandemic-related illness and deaths. Our findings
      suggest that school closings would not have a substantial effect on pandemic
      related outcomes in the absence of measures to reduce out-of-school contacts.
      However, if persons with influenzalike symptoms and their household contacts were
      encouraged to stay home, then rates of illness and death might be reduced by
      approximately 50%. By preventing ill LTCF residents from making contact with
      other residents, illness and deaths in this vulnerable population might be
      reduced by approximately 60%. Restricting the activities of infected persons
      early in a pandemic could decrease the pandemic's health effects.

PMID- 17553274
TI  - Spanish influenza in Japanese armed forces, 1918-1920.
AB  - With the recent outbreaks of avian influenza A (H5N1), the risk for the next
      influenza pandemic has increased. For effective countermeasures against the next
      pandemic, investigation of past pandemics is necessary. We selected cases
      diagnosed as influenza from medical records and hospitalization registries of
      Japanese army hospitals during 1918-1920, the Spanish influenza era, and
      investigated clinical features and circumstances of outbreaks. Admission lists
      showed a sudden increase in the number of inpatients with influenza in November
      1918 and showed the effect of the first wave of this pandemic in Tokyo. The death
      rate was high (6%-8%) even though patients were otherwise healthy male adults.

PMID- 17553275
TI  - Global distribution of Panton-Valentine leukocidin--positive methicillin
      resistant Staphylococcus aureus, 2006.
AB  - We determined the agr type, multilocus sequence type, protein A gene type (spa
      typing), toxin gene profile, and antimicrobial drug resistance profile of 469
      isolates of Panton-Valentine leukocidin-positive community-acquired methicillin
      resistant Staphylococcus aureus isolates (PVL-positive CA-MRSA). The isolates had
      been collected from around the world from 1999 through 2005 by the French
      National Reference Center for Staphylococci. We found that some continent
      specific clones described in 2003, such as clone ST8, have now spread all over
      the world. Likewise, some PVL-positive CA-MRSA have spread to several countries
      on various continents. New clones have emerged (e.g., ST377) on new genetic
      backgrounds. PVL-positive CA-MRSA that were usually susceptible to most
      antistaphylococcal antimicrobial agents have acquired new resistance determinants
      (e.g., to gentamicin) in certain countries. The major trait shared by all these
      clones is a short staphylococcal chromosomal cassette mec element of type IV or
      V.

PMID- 17553276
TI  - Genetic stasis of dominant West Nile virus genotype, Houston, Texas.
AB  - The accumulation and fixation of mutations in West Nile virus (WNV) led to the
      emergence of a dominant genotype throughout North America. Subsequent analysis of
      44 isolates, including 19 new sequences, from Houston, Texas, suggests that WNV
      has reached relative genetic stasis at the local level in recent years.

PMID- 17553277
TI  - Autochthonous transmission of Trypanosoma cruzi, Louisiana.
AB  - Autochthonous transmission of the Chagas disease parasite, Trypanosoma cruzi, was
      detected in a patient in rural New Orleans, Louisiana. The patient had positive
      test results from 2 serologic tests and hemoculture. Fifty-six percent of 18
      Triatoma sanguisuga collected from the house of the patient were positive for T.
      cruzi by PCR.

PMID- 17553278
TI  - Endpoints for lymphatic filariasis programs.
AB  - In 2000, annual mass administration of diethlycarbamazine and albendazole began
      in Leogane Commune, Haiti, to interrupt transmission of lymphatic filariasis
      (LF). After 5 years of treatment, microfilaremia, antigenemia, and mosquito
      infection rates were significantly reduced, but LF transmission was not
      interrupted. These finding have implications for other LF elimination programs.

PMID- 17553279
TI  - Genetic characterization of HPAI (H5N1) viruses from poultry and wild vultures,
      Burkina Faso.
AB  - Genetic analysis of highly pathogenic avian influenza (H5N1) viruses from poultry
      and hooded vultures in Burkina Faso shows that these viruses belong to 1 of 3
      sublineages initially found in Nigeria and later in other African countries.
      Hooded vultures could potentially be vectors or sentinels of influenza subtype
      H5N1, as are cats and swans elsewhere.

PMID- 17553280
TI  - Bluetongue in Belgium, 2006.
AB  - Bluetongue has emerged recently in Belgium. A bluetongue virus strain was
      isolated and characterized as serotype 8. Two new real-time reverse transcription
      quantitative PCRs (RT-qPCRs) that amplified 2 different segments of bluetongue
      virus detected this exotic strain. These 2 RT-qPCRs detected infection earlier
      than a competitive ELISA for antibody detection.

PMID- 17553281
TI  - Influenza vaccine effectiveness among US military basic trainees, 2005-06 season.
AB  - Virtually all US military basic trainees receive seasonal influenza vaccine.
      Surveillance data collected from December 2005 through March 2006 were evaluated
      to estimate effectiveness of the influenza vaccine at 6 US military basic
      training centers. Vaccine effectiveness against laboratory-confirmed influenza
      was 92% (95% confidence interval 85%-96%).

PMID- 17553282
TI  - Human sapovirus in clams, Japan.
AB  - Human sapovirus was detected in 4 of 57 clam packages by reverse transcription
      PCR and sequence analysis. This represents the first finding of sapovirus
      contamination in food. Closely matching sequences have been detected in stool
      specimens from patients with gastroenteritis in Japan, which indicates a possible
      food-to-human transmission link.

PMID- 17553283
TI  - Cryptosporidiosis decline after regulation, England and Wales, 1989-2005.
AB  - Since new drinking water regulations were implemented in England and Wales in
      2000, cryptosporidiosis has been significantly reduced in the first half of the
      year but not in the second. We estimate an annual reduction in disease of 905
      reported cases and approximately 6,700 total cases.

PMID- 17553284
TI  - Avian influenza viruses in water birds, Africa.
AB  - We report the first large-scale surveillance of avian influenza viruses in water
      birds conducted in Africa. This study shows evidence of avian influenza viruses
      in wild birds, both Eurasian and Afro-tropical species, in several major wetlands
      of Africa.

PMID- 17553285
TI  - MRSA transmission between cows and humans.
AB  - We isolated methicillin-resistant Staphylococcus aureus (MRSA) from cows with
      subclinical mastitis and from a person who worked with these animals. The bovine
      and human strains were indistinguishable by phenotyping and genotyping methods
      and were of a low frequency spa type. To our knowledge, this finding indicates
      the first documented case of direct transmission of MRSA between cows and humans.

PMID- 17553286
TI  - Human Babesia microti incidence and Ixodes scapularis distribution, Rhode Island,
      1998-2004.
AB  - Distribution of nymphal Ixodes scapularis in Rhode Island was used as a
      logistical regressor for predicting presence of human babesiosis. Although the
      incidence of babesiosis is increasing in southern Rhode Island, large areas of
      the state are free of babesiosis risk.

PMID- 17553287
TI  - Human bocavirus, a respiratory and enteric virus.
AB  - In Spain, human bocavirus (HBoV) was detected in 48 (9.1%) of 527 children with
      gastroenteritis at similar frequency as for children with respiratory illness
      (40/520, 7.7%). Fecal excretion adds new concern about the transmission of HBoV.
      To our knowledge, this report is the first to document HBoV in human feces.

PMID- 17553288
TI  - Antimicrobial drug resistance of Salmonella isolates from meat and humans,
      Denmark.
AB  - We compared 8,144 Salmonella isolates collected from meat imported to or produced
      in Denmark, as well as from Danish patients. Isolates from imported meat showed a
      higher rate of antimicrobial drug resistance, including multidrug resistance,
      than did isolates from domestic meat. Isolates from humans showed resistance
      rates lower than those found in imported meat but higher than in domestic meat.
      These findings indicate that programs for controlling resistant Salmonella spp.
      are a global issue.

PMID- 17553296
TI  - [Recognition of perplexity and misunderstand in diagnosis and treatment of
      chronic constipation].

PMID- 17553289
TI  - 16S rRNA methylase-producing, gram-negative pathogens, Japan.
AB  - To investigate the exact isolation frequency of 16S rRNA methylase-producing,
      gram-negative pathogenic bacteria, we tested 87,626 clinical isolates from 169
      hospitals. Twenty-six strains from 16 hospitals harbored 16S rRNA methylase
      genes, which suggests sparse but diffuse spread of pan-aminoglycoside-resistant
      microbes in Japan.

PMID- 17553297
TI  - [Gastrointestinal biomechanics--new perspectives in motility research].

PMID- 17553298
TI  - [Neoadjuvant chemotherapy of breast cancer].

PMID- 17553299
TI  - [An epidemiologic study of functional bowel disorders in adolescents in China].
AB  - OBJECTIVE: To explore the most common bowel frequency and the prevalence rates of
      functional bowel disorders among adolescents in China. METHODS: A questionnaire
      survey was conducted among 51,956 students from high and primary schools in 6
      Chinese cities distributed in the whole China collected by stratified,
      randomized, cluster sampling to study the epidemiology of functional bowel
      disorders. RESULTS: (1) 88.05% +/- 0.28% of the students had bowel frequency
      between 1 - 2 times/day and 1 time/two days. Girl students were found to have a
      lower bowel frequency than boy students (P < 0.01). (2) The prevalence rates of
      irritable bowel syndrome, chronic constipation, and chronic diarrhea were 20.19%
      (10 490), 25.92% (13 467), and 8.77% (4557) respectively. CONCLUSION: (1) The
      normal bowel frequency among adolescents in China may be defined as bowel
      movements between 1 - 2 times per day and 1 time per two days. (2) Irritable
      bowel syndrome, chronic constipation and chronic diarrhea are common disorders
      among the adolescents in China.

PMID- 17553300
TI  - [Effect of intestinal electrical stimulation on small bowel transit: experiment
      with healthy volunteers].
AB  - OBJECTIVE: To investigate the effect of intestinal electrical stimulation (IES)
      on small bowel transit. METHODS: Twelve healthy volunteers, 6 males and 6
      females, aged 22 - 23, underwent IES. A nasal-gastric tube with 2 ring electrodes
      on the tip was incubated into the duodenum via endoscope. 100 ml 1m Ci (99)Tc(m)
      mixed non-absorbable liquid was infused via the tube. During the course
      continuous real IES was conducted or the electrodes were connected to the
      stimulator but not with the power source (sham IES). Scanning with gamma-video
      camera was conducted every 10 seconds. The time for the isotope to enter the
      ileocecum first was measured so as to indicate the small bowel transit. Dyspeptic
      symptoms were scored by the subjects themselves. RESULTS: (1) The time for the
      isotopes to enter the ileocecum in real IES session was (28 +/- 10) min,
      significantly lower than that in sham IES session [(39 +/- 17) min, P < 0.05].
      (2) The dyspeptic symptom score during the real IES was 1.5, not significantly
      different from that before IES (1.0, P > 0.05), and the dyspeptic symptom score
      during the sham IES was 0.5, also not significantly different from that during
      real IES (P > 0.05). CONCLUSION: IES is capable of accelerating small bowel
      transit with no effect on dyspeptic symptoms, which suggests that IES may be a
      potential therapeutic method on intestinal motility disorders.

PMID- 17553302
TI  - [The role of protein kinase C-mediated phosphorylation of type III inositol 1, 4,
      5-triphosphate receptor in cholecystokinin octapeptide induced calcium
      mobilization in gastric antral smooth muscle cells].
AB  - OBJECTIVE: To study the effects of sulfated cholecystokinin octapeptide (sCCK-8S)
      on intracellular calcium release and extracellular calcium influx in gastric
      antral smooth muscle cells (SMC) and the mechanism thereof. METHODS: (1)
      Longitudinal muscle (LM) and circular muscle (CM) strips of gastric antrum and
      pylorus were isolated from SD rats and suspended in a tissue chamber to record
      the contractile responses by polyphysiography. (2) Immunoprecipitation,
      electrophoresis, and immunoblotting were used to detect the phosphorylation of
      type III inositol 1, 4, 5-triphosphate receptor (InsP(3)R(3)) in the SMCs. (3)
      The responsiveness of gastric SMC to CCK-8S was examined by using fura-2-loaded
      microfluorimetric measurement of intracellular calcium concentration ([Ca(2+)]i).
      (4) The current of L-type calcium channels (ICaL) was recorded by using patch
      clamp techniques. RESULTS: (1) Significant changes to CCK-8S were found in the
      mean contractile amplitude of the CM and frequency of LM of gastric antrum and
      could be suppressed by CCK-A receptor (CCK-AR) antagonist and ATPase inhibitors.
      (2) CCK-8S stimulation of SMC resulted in PKC-dependent phosphorylation of the
      InsP(3)R(3). (3) CCK-8S-evoked significant increase in [Ca(2+)]i [from (69 +/- 7)
      mol/L to (472 +/- 36) nmol/L, P < 0.01] could be suppressed by CCK-AR antagonist,
      ATPase inhibitors and protein kinase C (PKC) activator; whereas on condition that
      extracellular calcium was removed or L-type calcium inhibitor nifedipine was
      added a small but significant increase of [Ca(2+)]i could be still elicited by
      CCK-8S. (4) CCK-8S-intensified calcium current [from (-56 +/- 7) pA to (-89 +/-
      6) pA, P < 0.01] could be apparently inhibited by respective administration of
      nifedipine, ATPase inhibitors, and calcium dependent chloride channel (I(Cl-Ca))
      blocker (all P < 0.01). CONCLUSION: CCK-8S-evoked [Ca(2+)]i increase in gastric
      antral SMCs depends on the release of intracellular calcium stores, which is
      regulated by PKC mediated phosphorylation of InsP(3)R(3). The released
      intracellular calcium in turn activates the L-type voltage-dependent calcium
      channels (VDCC) through the activation of calcium dependent chloride channels,
      and ultimately results in the occurrence of contraction response of smooth
      muscles.

PMID- 17553303
TI  - [Effect of combined drug treatment on megacolon with severe constipation].
AB  - OBJECTIVE: To assess the effectiveness of combined drug treatment on megacolon
      complicated by severe constipation. METHODS: Ten patients with megacolon
      confirmed by barium enema examination, 4 males and 6 females, aged 38 (15 - 66),
      with a mean course of 10 years (2 weeks - 23 years), all complicated by severe
      constipation and 5 cases with colonic obstruction confirmed by X-ray examination,
      1 being diagnosed as with Hirschsprung' disease, 3 secondary to chronic
      constipation, 1 with diabetes mellitus, 1 with a history of anorectal
      malformation, 4 with colonic pseudo-obstruction, and 4 with colonic pseudo
      obstruction, were treated with combined conservative therapy including tegaserod
      (6 mg 2/d), polyethylene glycol (PEG) 4000 (20 - 40 g/d), and liuweianxiao
      (traditional Chinese medicine, 5 # 3/d). Colon enema was used in the first week
      if necessary. Follow-up was conducted for 1 - 7 months. The major clinical data
      included bowel symptoms, complications and adverse effects. RESULTS: After 1 - 2
      weeks of treatment, properties of feces, defecation times, defecation difficulty,
      and abdominal symptoms, and X-ray findings were all notably improved. No relapse
      of colonic obstruction was found. The 5 patients with colonic obstruction all
      showed release. Regarding adverse effect, mild diarrhea was found in 2 cases and
      was relieved when the dosage was decreased. CONCLUSION: Combined drug treatment
      including tegaserod, PEG 4000 and traditional Chinese medicine is effective in
      treating megacolon with severe constipation and may help avoid surgical
      treatment.

PMID- 17553304
TI  - [Folate-poly-L-lysine-Gd-DTPA as MR contrast agent for tumor imaging via folate
      receptor-targeted delivery].
AB  - OBJECTIVE: To study folate-conjugated Gd-DTPA-Poly-L-Lysine (folate-PL-Gd-DTPA)
      as MR targeting agent to tumor cells via folate receptor, to evaluate feasibility
      and effectiveness by observing MR signal variations and imaging feature of
      pulmonary tumor xenografts in nude mice using this contrast material. METHODS:
      (1) Using Poly-L-Lysine (PL) as linker, after PL was tethered with caDTPA,
      GdCl(3) was added to label DTPA-PL, then PL-Gd-DTPA was conjugated to folate, a
      specific MR contrast agent, was thus prepared. (2) Using high performance liquid
      chromatography (HPLC) to evaluate the conjugate purity, and the ICP-AES to test
      Gd(3+) concentration, while the activity evaluated by competitive folate receptor
      binding with folic acid. (3) Folate-PL-Gd-DTPA as specific contrast agents (study
      group, n = 6) and Gd-DTPA as non-specific contrast agents (control group, n = 4)
      was injected respectively into caudal vein of the nude mice which was pulmonary
      tumor xenografts as experimental model in the study. MRI was performed with plain
      scans, enhanced scans at 30 minutes, 3 hours, 6 hours, 14 hours, 24 hours, 38
      hours, 48 hours, 62 hours and 72 hours after the success of injection. Signal
      intensities of tumors and muscles were measured. RESULTS: (1) folate-PL-Gd-DTPA
      was successfully synthesized with high affinity to folate receptor and high
      concentration of Gd(3+) (56 Gd(3+)/folate). (2) folate-PL-Gd-DTPA had an
      excellent tumor selectivity in pulmonary tumor xenografts in the animal model.
      After injection, the tumor signal intensity in the study group was significantly
      higher than that observed before injection; An average intensity increase of
      125.4% was observed from pre-contrast to post-contrast images of the tumor, which
      was observed at 24 - 48 hours after injection; The muscle signal intensity at any
      time-point after injection showed no statistically difference with that observed
      before injection. In control group, the tumor signal intensity showed
      statistically difference with that observed before injection at 0.5 hour and 3
      hours, the biggest difference appeared at 0.5 hour; The muscle signal intensity
      at 0.5 hour time-point showed statistically difference with that observed before
      injection. CONCLUSION: Folate-PL-Gd-DTPA could be combined to tumor cells
      appetencially via folate receptor and significantly targeted to tumor cells with
      rich folate receptors for MR imaging.

PMID- 17553305
TI  - [Magnetic resonance imaging of magnetically labeled endothelial progenitor cells
      homing to the injured endothelium].
AB  - OBJECTIVE: Accumulating evidence suggests that the endothelial progenitor cells
      (EPCs) can reendothelialization the injured endothelium. Superparamagnetic iron
      oxide particles are being used for intracellular magnetic labeling of cells and
      in vivo cells tracking. The aim of this study was to investigate the possibility
      of depict and track magnetically labeled EPCs in vivo for carotid artery
      endothelium injured New Zealand White rabbit model by 1.5 T magnetic resonance
      imaging system after EPCs transplantation. METHODS: The EPCs of New Zealand White
      rabbit were isolated, confirmed, expanded and then incubated with home
      synthesized Fe2O3-PLL for 24 hours, Prussian blue stain was performed for showing
      intracellular irons. The model of carotid arterial injury was performed by 2.5 F
      balloons. The group A of 5 rabbits were transplanted with magnetically labeled
      EPCs, the group B of 5 rabbits were received fluorescent-labeled EPCs, and 5
      rabbits of the group C were received the same volume of saline injection
      immediately after the carotid artery endothelium was injured. The transfused EPCs
      were strictly restricted to the injury site. MR imaging and histology were
      performed and compared 7 days late. RESULTS: The Epcs labeling efficiency of
      Fe2O3-PLL was more than 95% identified by Prussian blue stain. Seven days after
      the transplanted of EPCs, only in group A, the injured endothelium of carotid
      artery wall had the signal intensity loss in T(2)WI MRI, which corresponding to
      the injured endothelium where the most Prussian blue staining-positive cells were
      in histopathological analyses. While histopathological slides showed that the
      fluorescence-positive cells in the injured endothelium which had been
      transplanted Dil labeled EPCs also. The group C was either in negative.
      CONCLUSION: The rabbits endothelial progenitor cells can be effectively labeled
      with Fe2O3-PLL, 1.5 T magnetic resonance imaging system could depict and monitor
      the magnetically labeled endothelial progenitor cells homing to the injured
      endothelium of the artery, which may have much more potential values for studying
      the engraftment of EPCs in cardiovascular disease.

PMID- 17553306
TI  - [Autologous mononuclear bone marrow cell transplantation by intracoronary route
      for patients with ischemic heart disease: observation of 2-years follow-up].
AB  - OBJECTIVE: To investigate the long-term effect and safety of intracoronary
      autologous bone marrow mononuclear cell (BMMC) transplantation in patients with
      ischemic heart disease (IHD). METHODS: Seventy-six patients with IHD, 26 patients
      with acute myocardial infarction (AMI) and 26 patients with chronic ischemic
      heart failure (CIHF), underwent routine treatment plus intracoronary autologous
      BMMC transplantation, and 24 patients, including 10 patients with AMI and 14
      patients with CIHF underwent routine treatment as controls. Autologous BMMC
      transplantation was performed via a balloon catheter placed into the infarct
      related artery during balloon dilatation by high pressure infusion to occlude the
      artery, which was performed 6 - 8 times for 2 minutes each with 2-minute interval
      or via a balloon catheter without occluding the infarct-related artery. Follow-up
      was conducted for 2 years. RESULTS: The surgery was safety without major
      periprocedural complications. There were no other new arrhythmias found by Holter
      recorder during the 2-years follow-up. In the AMI patients receiving BNNC
      transplantation, the left ventricular ejection fraction (LVEF) 1 and 2 years
      later increased by 5.79% (P < 0.05), 3.79% (P > 0.05) respectively; but there was
      no change in left ventricular end diastolic volume (LVEDV) and left ventricular
      end systolic volume (LVESV). The LVEF 1 and 2 years later of the control group
      increased by 8.8% and 9.2% respectively (both P < 0.01) and the LVESV 1 and 2
      years later decreased by 20.4% and 27.8% respectively (both P < 0.05), the
      myocardium defect area 2 years later was not significantly different from that 3
      months later. The heart function of the control group became markedly worse.
      CONCLUSION: Autologous BMMC intracoronary transplantation is safe and effective,
      especially in patients with CIHF.

PMID- 17553307
TI  - [Correlation of CD40 gene polymorphisms with acute coronary syndrome,
      hypertension and diabetes].
AB  - OBJECTIVE: To investigate the correlation of CD40-E1SNP (-1C/T) and CD40-E4SNP
      with acute coronary syndrome (ACS), hypertension and diabetes in Chinese Han
      population. METHODS: The allele frequencies of CD40-E1SNP (-1C/T) and CD40-E4SNP
      were assayed by polymerase chain reaction-restriction fragment length
      polymorphism and DNA sequence technology in 160 definite ACS patients and 92
      controls with negatively coronary arteriography. Multivariate logistic regression
      models were used to analyzed the interaction between the CD40 gene polymorphisms
      and hypertension and diabetes. RESULTS: CD40-1C allele frequency of the ACS group
      was 0.606, significantly higher than that of the control group (0.489, P < 0.01),
      while the T allele frequency of the ACS group was 0.394, significantly lower than
      that of the control group (0.511, P < 0.01). The frequency of CC genotype was
      much higher in the ACS group than in the control group (P < 0.01). C allele
      increased the risk of ACS (OR = 1.608, 95% CI: 1.12 - 2.32, P = 0.011). After
      adjustment of confounding variables, such as age, sex, and body mass index, the
      binary logistic analysis showed a significant gene-environment interaction (P <
      0.05). The OR value were: 1.608 for C allele (95% CI: 1.12 - 2.32, P < 0.05),
      5.71 for C allele-with hypertension (95% CI: 1.12 - 29.08, P < 0.05), 1.44 for C
      allele-without diabetes (95% CI: 1.12 - 5.13, P < 0.01), and 2.35 for C allele
      with diabetes (95% CI: 1.47 - 4.82, P < 0.01). Expression of CD40-E4SNP was not
      found in these subjects. CONCLUSION: CD40-1C/T polymorphism is associated with
      ACS in Chinese people. The -1C allele carriers have higher risk of ACS if they
      get hypertension or diabetes; CD40-E4SNP may not exist in Chinese people.

PMID- 17553309
TI  - [The role of stromal cell derived factor-1/CXCR4 biological axis in tumor
      metastasis of non-Hodgkin lymphoma].
AB  - OBJECTIVE: To study the expression of stromal cell derived factor-1 (SDF-1) and
      its receptor CXCR4 in non-Hodgkin lymphoma (NHL), and to investigate the role of
      this biological axis in tumor metastasis of NHL. METHODS: Specimens of bone
      marrow were collected from 4 patients with NHL with bone marrow infiltration and
      4 cases of NHL without bone marrow infiltration, and 4 patients with benign
      hepatopathy with normal myelogram. Lymphoma specimens were collected from 7 cases
      of NHL and 3 cases of reactive proliferative lymphadenitis. The level of SDF
      1alpha mRNA in the stromal cells of bone marrow and lymph node were determined by
      RT-PCR. The CXCR4 expression on lymphoma cells freshly isolated from bone marrow
      and lymph node of the NHL patients were studied by flow cytometry. Transwell
      assay was performed, the upper chamber being added with suspension of cells newly
      isolated from lymph nodes or bone marrow undergoing co-incubation with ant-CXCR4
      monoclonal antibody or not, and the lower chamber added with culture fluid with
      or without recombinant human SDF-1alpha (rhSDF-1alpha). The migration rate of the
      primary lymphoma cells towards rhSDF-1alpha was calculated. RESULTS: The
      expression levels of CXCR4 on the lymphoma cells isolated from the bone marrow
      involved or not involved by NHL were both significantly higher than that of the
      mononuclear cells from normal bone marrow (both P < 0.01), whereas the CXCR4
      expression level on the lymphoma cells from the lymph nodes of the NHL patients
      was also significantly higher than that of the mononuclear cells from the lymph
      nodes of reactive proliferative lymphadenitis (P < 0.01). The SDF-1alpha mRNA
      expression level in the stromal cells isolated from the bone marrow involved by
      NHL was significantly higher than those of the stromal cells of bone marrow not
      involved by NHL and the normal bone marrow (both P < 0.01). Moreover, the SDF
      1alpha expression level in the lymph node stromal cells of all the NHL patients
      was also significantly higher than that of the patients with reactive
      proliferative lymphadenitis (P < 0.01). Transwell assay revealed that all three
      kinds of primary lymphoma cells migrated towards rhSDF-1alpha effectively, and
      this migration was markedly inhibited by the addition of anti-CXCR4 monoclonal
      antibody to the lymphoma cells (all P < 0.01). CONCLUSION: SDF-1/CXCR4 axis plays
      a uniquely important biological role in mediating tumor metastasis of NHL.

PMID- 17553310
TI  - [Clinical application of Meek micrograft technique].
AB  - OBJECTIVE: To explore the clinical application of the transplantation of the Meek
      autograft. METHODS: Meek autografts were transplanted on the full-thickness
      wounds of 10 patients, including 9 cases of burn and 1 case of necrofascitis,
      with the area of 8.6% (2% - 28%) of the total body surface, and the average of
      the area was. Meek skin graft was placed on the wounds immediately after
      escharectomy (in 4 cases), 4 - 16 days after tangential excision (in 4 cases), or
      on the clean wound granulation 35 - 45 days after the injury (in 2 cases). 108
      pieces of extending gauze of different rates were used. As comparison, Stamp-like
      grafts, micrografts, or net-like graft were used in different places of the same
      bodies in 5, 4, and 1 case respectively. RESULTS: The operation time of Meek
      micrograft technique was 9 - 60 minutes. The survival rate of the Meek graft was
      93% (100% in 8 cases for, 80% in 1 case, and 50% in 1 case). The operation time
      of the other operation techniques was 30 - 240 minutes. The average survival rate
      of the other operation techniques was 86% (100% in 2 cases, 90% - 98% in 4 cases,
      80% in 3 cases, and 50% in 1 case). CONCLUSION: Meek autograft is suitable for
      all of the full-thickness wound except bone-exposure wound, including the wound
      of major burns. This technique uses less skin to repair the wound and the time
      for epithelization is shorter than that of the traditional methods. The staff and
      time needed for the operation are less. The outcome is good and the healed wound
      is fine-looking.

PMID- 17553311
TI  - [Pharmacodynamics of China-made rapamycin-polylactide-co-glycolide peripheral
      arterial eluting stent membrane: in vitro experiment].
AB  - OBJECTIVE: To evaluate the property and drug releasing pattern of the China-made
      rapamycin-polylactide-co-glycolide (PLGA) peripheral arterial eluting stent
      membrane. METHODS: Rapamycin was put into PLGA so as to made rapamycin-PLGA
      complex. Twelve nickel-titanium self-expanding stents were dipped into the
      complex to make drug-eluting stents. Somatotype microscope was used to observe
      the macro-form of the surface of the eluting membrane, and atom force microscope
      was used to analyzing the three-dimensional appearance and surface roughness of
      the membrane. The stents were put into fluid with platelets to observe the form
      of platelets blood compatibility by scanning electron microscopy. The extra
      degradation of the coating layer, by putting the stents into a simulation system
      of internal environment. High efficacy liquid chromatography was used to study
      the pharmacokinetics of the stents. Standard curve and stimulative curve, and
      drug release curve of multiple stents were drawn and analyzed. RESULTS: The
      membranes of all 12 stents had smooth surfaces and regular thickness and no
      membrane falling-off was observed. The platelets on the surfaces of the stents
      were inactivated and the number of the platelets adhering to the surfaces of the
      stents were reduced obviously in comparison with the blank control. PLGA degraded
      by 20% within 2 weeks and then the degradation speed accelerated until complete
      degradation occurred within 6 weeks, and the drug releasing lasted more than 50
      days. The percentage of accumulative drug release was 11.02% in 24 hours, 41.23%
      in 9 days, and 79.44% in 30 days. CONCLUSION: Smooth and even, and capable of
      controlling the drug release, rapamycin-PLGA peripheral arterial eluting stent
      membrane coating has the potential clinical value in preventing in-stent
      stenosis.

PMID- 17553312
TI  - [Electrophysiology of two human hyperpolarization activated cyclic nucleotide
      gated potassium channels expressed in HEK293 cells].
AB  - OBJECTIVE: To express the human HCN2 and HCN4 genes in HEK293 cells and
      investigate the electrophysiology of the expressed channel protein. METHODS: cDNA
      encoding human HCN2 or HCN4 gene was ligated into a shuttle vector pAdTrack-CMV.
      Homologous recombination was performed in Escherichia coli of the line BJ5183.
      Human embryonic kidney cells of the line 293 (HEK293 cells) were cultured and
      transfected with the positive recombinant adenovirus plasmid. Then the HEK293
      cells were infected by AdhHCN2 or AdhHCN4 and the whole cell hyperpolarization
      activated currents were recorded in HEK293 cells transfected with hHCN2 and
      hHCN4. RESULTS: If-like currents could be found in the HEK293 cells transfected
      with hHCN2 and hHCN4. The channels were activated by hyperpolarized potentials.
      Boltzmann equation showed that the half-activation voltage of the hHCN2 and hHCN4
      channels were -114.8 mV +/- 3.3 mV and -125.9 mV +/- 2.9 mV respectively (P =
      0.024). The reversal slope factors of the hHCN2 and hHCN4 channels were 11.1 mV
      +/- 1.2 mV and 13.7 mV +/- 1.3 mV respectively (P = 0.22). The activation
      kinetics was faster in hHCN2 than in hHCN4, with the activation constants at -110
      mV being 0.99 s +/- 0.21 s and 8.47 s +/- 2.85 s respectively. The relative
      permeation ratio for sodium and potassium were 0.40 and 0.34 respectively in
      these two channels. Caesium chloride of the concentration of 2 mmol/L prominently
      inhibited both currents. CONCLUSION: The target genes hHCN2 and hHCN4 are
      successfully expressed in HEK293 cells, and the expressed functional channels
      have profoundly different activation kinetics.

PMID- 17553313
TI  - [Role of MG132, a proteasome inhibitor, in inducing expression of costimulatory
      molecules CD86 in leukemic cells and its effect on allogeneic mixed lymphocyte
      reaction].
AB  - OBJECTIVE: To investigate the role of proteasome inhibitors MG132 in the inducing
      the expression of the costimulatory molecules CD80 and CD86 in leukemia cells and
      its effect on allogeneic mixed lymphocyte reaction. METHODS: Acute myelocytic
      leukemia cells of the line HL-60 and chronic myelocytic leukemia cells of the
      line K562 were cultured. 7-AAD staining and flow cytometry (FC) were used to
      examine the viability of the cells. MG132, a proteasome inhibitor, of the
      concentrations of 2 or 3 micromol/L was added into the culture fluid of HL-60
      cells for 24 h and 48 h respectively and then annexin V/7-AAD staining and FC
      were used to detect the apoptosis of the cells. HL-60 and K562 cells treated with
      1 micromol/L MG132 for 24 h and 48 h respectively, anti-CD80 and anti-CD86
      antibodies were added, then FC was used to detect the expression of CD80 and
      CD86. The mRNA expression of CD86 in the HL-60 cells treated with 1 micromol/L
      MG132 was examined by RT-PCR. HL-60 and K562 cells were treated by 1 micromol/L
      MG132 for 48 h and then underwent irradiation of 75 Gy Co-60 to kill the cells
      with their antigenicity preserved. Peripheral blood mononuclear cells (PBMNC) of
      healthy volunteers, as reactive cells, were isolated and inoculated into the Co
      60 treated HL-60 and K532 cells of different concentrations, as stimulating
      cells, for 5 d, CCK-8, a new agent to detect the cell viability, was added for 4
      h, and then the A value of absorbance was measured at the wave length of 450 nm
      of enzyme labeling instrument. Control groups were set up for all tests. RESULTS:
      The cell viability rates of the HL-60 cell treated with 1 micromol/L MG132 for 24
      h and 48 h were 92.95% and 85.87% respectively. The apoptotic rats of the HL-60
      cells treated with MG132 were increased dose- and time-dependently. Before MG132
      treatment K562 cells did not express CD86, and the CD86 expression of the HL-60
      cells was up-regulated time-dependently (all P < 0.01). The mRNA expression of
      CD86 in the HL-60 treated with MG132 was up-regulated time-dependently (P <
      0.01). CKK8 test showed that the proliferation level of PBMNC gradually increased
      along with the concentration of HL-60 cells treated with MG132 and reached its
      peak when the concentration of the HL-60 cells was 1 x 10(5) (P < 0.01). No
      remarkable proliferation of PBMNC was seen in the K562 groups no matter if the HL
      60 cells had been treated with MG132. CONCLUSION: MG132 induces the expression of
      costimulatory molecule CD86 in the HL-60 cells, thus improving the proliferation
      of PBMNC.

PMID- 17553314
TI  - [The effect of selectively inhibiting the nuclear factor kappaB activation on
      survivin expression in leukemic cells].
AB  - OBJECTIVE: To investigate the highly specific proteasomal inhibitor MG132-induced
      apoptosis and its effect on nuclear factor (NF)-kappaB activation and survivin
      expression in leukemic K562 cell line. METHODS: leukemic cells of the line K562
      were cultured and divided into 2 groups: treatment group, undergoing co
      incubation with MG132 of the concentrations of 2, 4, 6, and 8 micromol/L
      respectively for 24 hours, and control group without treatment of MG132.
      Apoptosis was detected by examination of cell morphology and flow cytometry.
      Survivin expression and NF-kappaB activation were analyzed by immunocytochemistry
      and Western blotting. RESULTS: MG132 induced apoptosis of the K562 cells dose
      dependently. Both survivin and NF-kappaB were highly expressed in the K562 cells.
      Compared with the control group, K562 cell treated with MG132 at the
      concentrations of 2, 4, 6, and 8 micromol/L for 24 hours showed the decrease of
      NF-kappaB activation to 75.0% +/- 3.7%, 59.9% +/- 5.3%, 45.4% +/- 5.7%, and 25.0%
      +/- 4.2% respectively, and decrease of survivin expression to 90.9% +/- 10.1%,
      66.7% +/- 5.2%, 45.4% +/- 5.7%, and 30.3% +/- 6.6% respectively. Downregulation
      of survivin expression was closely correlated with the inhibition of NF-kappaB
      activation (Pearson correlation coefficient = 0.989, P < 0.01). CONCLUSION: MG132
      induces apoptosis of leukemic cells, and effectively inhibits the NF-kappaB
      activation accompanied by the downregulation of survivin expression.

PMID- 17553318
TI  - Dermatological disorders related to cultural practices in black Africans of
      Sierra Leone.
AB  - OBJECTIVE: To describe various skin manifestations directly or indirectly related
      to the prevalent cultural practices in the local community of black Africans of
      Sierra Leone. STUDY DESIGN: An observational study. PLACE AND DURATION OF THE
      STUDY: Eastern province (Kenema) of Sierra Leone from November 2004 to October
      2005. PATIENTS AND METHODS: Local black patients of all age groups presenting in
      Dermatology Outpatient Department of Pak Field Hospital (established as a part of
      UN peacekeeping mission in Sierra Leone) were included. After clinical history
      and physical examination, lesions were photographed. Laboratory investigations
      were carried out when indicated. Skin diseases were broadly classified into two
      major categories i.e. related to cultural practices and not related to cultural
      practices. Non-black settlers in the area and UN troops were excluded. Data was
      recorded and analyzed by Microsoft Excel. RESULTS: A total of 3011 patients
      belonging to different local tribes having a variety of skin disorders were seen
      during the study period. Patients ranged from 1 month to 73 years of age with
      almost equal gender ratio. Vast majority were from very low socioeconomic group.
      Skin manifestations related to cultural practices were seen in more than 20%
      patients and most prevalent were alopecia and hypertrophic scars followed by
      pomade acne, pseudofolliculitis and contact dermatitis. CONCLUSION: Prevalent
      cultural practices in black Africans do play a role in causation of various skin
      disorders. For a dermatologist, it becomes imperative to be cognizant of the
      signs and symptoms associated with these practices for proper diagnosis and
      appropriate treatment.

PMID- 17553319
TI  - Predictive value of Rockall score for rebleeding and mortality in patients with
      variceal bleeding.
AB  - OBJECTIVE: To validate Rockall scoring system for in-hospital rebleeding and
      mortality in cirrhotic patients with variceal bleed. STUDY DESIGN: Cohort type of
      case series. PLACE AND DURATION OF STUDY: It was carried out at the Department of
      Gastroenterology and Hepatology, Shaikh Zayed Hospital, Lahore, from March 2005
      to March 2006. PATIENTS AND METHODS: All cirrhotic patients presenting with upper
      GI bleeding and later found to have variceal source of bleeding on endoscopy were
      included. Clinical and endoscopic features were noted to calculate Rockall score.
      After giving appropriate pharmacological and endoscopic therapy, patients were
      followed for rebleeding or death till discharge from hospital. Linear regression
      analysis was used to determine predictive value of score and discrimination was
      evaluated by calculating the area under the receiver operating characteristic
      (ROC) curve. RESULTS: A total of 402 patients were included. Mean age was 52.57
      (+/-11.39) and male to female ratio was 2:1(269/133). Esophageal varices were
      source of bleeding in 340 (84.5%), gastric fundal varix in 44 (11%) and ectopic
      duodenal varix in 3 (0.9%) patients. Both esophageal and gastric varices were
      present in 15 (3.6%) patients. In-hospital mortality was 6.7% while 22 (5.5%)
      patients had rebleeding. Rockall score was found to have good predictive value
      for mortality (p-value<0.001 and area under curve AUC 0.834) and in-hospital
      rebleeding (p-value<0.001 and AUC 0.798). CONCLUSION: Rockall scoring system has
      good predictive and discriminative value for in-hospital rebleeding and mortality
      in patients with variceal bleeding due to cirrhosis.

PMID- 17553320
TI  - A clinicopathological study of necrotizing fasciitis--an institutional
      experience.
AB  - OBJECTIVE: To describe the clinicopathological features in necrotizing fasciitis
      with evaluation of its clinical presentation, diagnostic criteria and mortality
      rate. DESIGN: A case series, observational study. PLACE AND DURATION OF STUDY:
      Kasturba Medical College Hospital, Manipal, India, from January 2003 to May 2005.
      PATIENTS AND METHODS: All patients meeting clinical and/or histopathologic
      criteria for necrotizing fasciitis were included. Patients were studied with
      particular importance to the mode of presentation, associated co-morbid
      conditions, relevant investigations, histopathological report, modalities of
      treatment and final outcome. RESULTS: A total of 38 patients were studied. The
      major cause of infection was idiopathic/primary. The average duration of symptoms
      at presentation was 10.07 days. The specific signs such as bullae and blistering
      were seen in 18 patients (47.3%). Of the infections, 19 (50%) were monomicrobial
      and 15 (39%) were polymicrobial. The most common complication seen was systemic
      sepsis with 9 patients (23.6%), of which 4 patients (10.5%) developed septicemic
      shock, 3 patients (7.8%) developed acute renal failure, 1 patient (2.6%)
      consolidation with pleural effusion and 2 patients (5.2%) had acute myocardial
      infarction. The mortality was 21%. CONCLUSION: The successful treatment of
      necrotizing fasciitis lies in early diagnosis and aggressive surgical
      debridement. Diabetes mellitus and other pre-morbid conditions increase the risk
      of mortality. The presence of bullae and blistering, foul smelling discharge and
      discolouration of skin raised the suspicion of necrotizing fasciitis. Findings at
      surgical exploration and skin biopsy are the only reliable means of diagnosis.

PMID- 17553321
TI  - Comparison of diagnostic accuracy of non-invasive tests for Helicobacter pylori
      infection in children.
AB  - OBJECTIVE: To compare urea breath and stool antigen in children, with
      histological diagnosis for Helicobacter pylori (H.pylori) infection. STUDY
      DESIGN: Cross-sectional study. PLACE AND DURATION OF STUDY: From June 2005 to
      December 2005 carried out at KRL Hospital, Islamabad and Children Hospital, PIMS,
      Islamabad. PATIENTS AND METHODS: Children between 3 and 15 years of age reporting
      in pediatric outpatient department with upper gastrointestinal symptoms were
      included. All the participating children underwent an upper gastrointestinal
      endoscopy and 3 tests namely: histopathological identification of H. pylori (the
      traditional gold standard), urea breath test and stool antigen test were carried
      out on each child. The sensitivity, specificity, and positive predictive values
      were calculated for each noninvasive test used in the study. RESULTS: A total of
      54 patients completed the study with a mean age of 8.2 years. On histological
      examination, 72% (39) were positive for H. pylori infection. On gross endoscopic
      examination, only 9 patients had signs of gastritis as compared to 39
      histological positives. The sensitivity, specificity and positive predictive
      value of stool antigen test were: 77%, 73% and 89% respectively whereas the same
      for urea breath test were: 79%, 80% and 91% respectively. CONCLUSION: Both the
      noninvasive tests were found to be sensitive and specific as compared with
      histological identification, for the diagnosis of H. pylori in our pediatric
      population. The accuracy of urea breath test was better than the stool antigen
      test but later was easier to perform and could fulfill the criteria for a rapid
      bedside diagnostic test.

PMID- 17553322
TI  - Pulmonary function tests: normal values in non-smoking students and staff at the
      Aga Khan University, Karachi.
AB  - OBJECTIVE: To estimate normal values of peak expiratory flow rate (PEFR), forced
      expiratory volume in first second (FEV1), forced vital capacity (FVC) and ratio
      between FEV1/FVC among non-smoking staff and students at The Aga Khan University
      (AKU) Hospital, Karachi, and to study the effect of age, gender and body mass
      index (BMI) on these variables. DESIGN: A cross-sectional study. PLACE AND
      DURATION OF STUDY: This study was conducted at the Multidisciplinary Laboratory
      (MDL) of AKUH, Karachi from May to November 2005. PATIENTS AND METHODS: Two
      hundred forty-one healthy never smokers were approached through non-probability
      convenient sampling among the staff and students of AKU and were screened through
      a questionnaire. Data from 200 subjects was used for analysis. Subjects were
      excluded if pregnant, body mass index (BMI) not ranging from 17-25, FEV1/FVC%
      less than 70 or with non-reproducible results. The mean values of FVC, FEV1,
      FEV1/FVC% and PEFR among males and females in different ages were compared by 't'
      test. Linear regression was applied to study the effect of age and BMI on the
      outcome variables. RESULTS: Mean FVC, FEV1 and PEFR were found to be higher in
      males than the females in all the age groups, the difference in FVC was
      significantly higher in the age groups of less than 20 years and 20-29 years
      (2.09L, CI: 1.27-2.92) and (1.51L, CI: 1.29-1.73) respectively. The above
      spirometric values declined with age and increased with height. Increase in age
      by one year resulted in 0.051 L decline in FVC (CI: -0.056, -0.034) whereas
      increase in height by a centimeter improved the FVC by 0.044L (CI: 0.03, 0.056).
      CONCLUSION: The mean FVC, FEV1 and PEFR were higher in males in each age group.
      Females had higher FEV1/FVC%. Height had positive linear relationship and age was
      inversely related whereas BMI was not significantly associated with these
      variables. In order to generalize these reference values, a larger study
      following the ATS criteria is needed.

PMID- 17553323
TI  - Mini-open cholecystectomy in the management of cholelithiasis.
AB  - OBJECTIVE: To analyze the outcome of open mini-cholecystectomy in terms of
      operative success and complications. STUDY DESIGN: Retrospective review of
      record. PLACE AND DURATION OF STUDY: Shifa International Hospital, Islamabad,
      from January 2002 to September, 2005. PATIENTS AND METHODS: All the patients who
      underwent mini-open cholecystectomy for cholelithiasis during the study period
      were reviewed. The data was collected on a computerized proforma. The patients
      undergoing classical open cholecystectomy were excluded. Statistical analysis was
      performed using SPSS for Windows version 11. RESULTS: A total of 200 cases were
      operated (180 females, 20 males; M:F ratio 1:9). The mean age was 43 years (range
      21-72 years). The average operating time was 45 minutes. Complications included
      biliary leak in one patient (0.5%), bleeding 1 (0.5%), wound infections 4 (2%)
      and death in one case (0.5%). The overall rate of complications was 3.5%. There
      were 5 patients who required extension of the incision for reasons like carcinoma
      gallbladder (1), control of bleeding (1), bad adhesions (1), difficult anatomy
      (1) and biliary leak from the liver bed (1). The mean hospital stay was 1.5 days
      (range 1-3 days). CONCLUSION: Mini-open cholecystectomy appears to be a safe and
      has its application where laparoscopic facilities are not available.

PMID- 17553324
TI  - Simultaneous kissing stents for the treatment of left main stenosis in
      cardiogenic shock.
AB  - Significant narrowing of the left main coronary artery puts the patient at high
      risk, since occlusion of this vessel, if unprotected by collateral flow or a
      patent bypass graft to either the left anterior descending or circumflex artery,
      compromises flow to approximately 75% of the left ventricle. Percutaneous
      coronary intervention of left main coronary artery may be the only life saving
      procedure. There are limited data on the general use of percutaneous intervention
      (PCI) in patients with acute myocardial infarction (MI) due to left main disease.
      Small series have noted in-hospital mortality rates of 30 to 35 percent following
      PCI with or without stenting. Moreover, cardiogenic shock secondary to acute MI,
      in patients with left main coronary artery disease, carries a very high
      mortality. Treatment options are limited especially when emergent coronary artery
      bypass surgery is not an option. We report a case of emergency angioplasty of
      left main coronary artery with simultaneous kissing stent technique in
      cardiogenic shock.

PMID- 17553325
TI  - Emergency laparoscopic cholecystectomy for acute empyema of the gallbladder in
      pregnancy.
AB  - This report describes a pregnant patient on whom emergency laparoscopic
      cholecystectomy was performed for empyema gallbladder. The patient was in her
      second trimester of pregnancy. The distended gallbladder was decompressed before
      dissection was commenced. There was no mortality, morbidity or conversion. There
      were no complications for either mother or child related to general anesthesia.

PMID- 17553326
TI  - Benign nerve sheath tumor of stomach.
AB  - Gastrointestinal mesenchymal tumors are a group of tumors, which originate from
      the mesenchymal stem cells of the gastrointestinal tract. Gastric schwannoma is a
      very rare gastrointestinal mesenchymal tumor, which represents only 0.2% of all
      gastric tumors and 4% of all benign gastric neoplasms. We report a 55 years old
      lady who suffered from pain epigastrium, vomiting, occasionally with blood, loss
      of appetite and weight loss. Endoscopic examination showed a round submucosal
      tumor with a central ulceration along the greater curvature of the stomach. The
      pathological examination revealed a picture of spindle cell tumor.
      Immunohistochemical stain was strongly positive for S-100 protein stain, and non
      reactive for CD34, CD117, consistent with benign nerve sheath tumor of stomach
      i.e. gastric schwannoma.

PMID- 17553327
TI  - Epithelioid hemangioendothelioma of the liver.
AB  - Epithelioid hemangioendothelioma is an intermediate grade malignant neoplasm of
      vascular origin. The tumor involves the liver and lungs, but other organs are
      affected too. The key to the diagnosis is identification of cells of endothelial
      origin containing Factor VIII R antigen. Surgical resection of isolated lesions
      is the treatment of choice; with unpredictable results reported for chemotherapy,
      radiotherapy, and resection of multiple lesions. The prognosis is very variable,
      and ranges from few months to more than 25 years.

PMID- 17553328
TI  - Static pulmonary nodules from thyroid malignancy.
AB  - Papillary carcinoma of thyroid tends to be indolent. This is an unusual case of
      papillary carcinoma of thyroid with asymptomatic pulmonary metastasis for more
      than a decade, finally presenting with mild respiratory symptoms in a 21-year-old
      female. Fine needle aspiration and cytology (FNA-C) of a nodule in the lungs
      revealed features consistent with a papillary carcinoma of thyroid. Confirmed on
      thyroidectomy specimen. She subsequently received Iodine-131 (I131). A follow-up
      radio-iodide scan, 48 hours after, revealed diffuse uptake within the lung
      parenchyma. With static nodular shadowing on radiograph, a metastatic origin, in
      particular that of the thyroid, should be considered. I131 scintigraphy can help
      support the diagnosis of carcinoma of thyroid.

PMID- 17553329
TI  - Malignant hypertension in a patient with end of stage renal disease (ESRD)
      treated by renal transplant.
AB  - Control of hypertension is often a problem in the management of end stage renal
      disease (ESRD). Multiple modalities of treatment are required to prevent
      cardiovascular and cerebrovascular mortality and morbidity. These include fluid
      and salt restriction, multidrug regimes and dialysis. We report a case of young
      25 years old patient, admitted with chronic renal failure, complicated by
      malignant and refractory hypertension, not responding to hemodialysis and
      antihypertensive agent. During stay in hospital, patient also had intracerebral
      hemorrhage, fits due to uncontrolled hypertension requiring ventilatory support
      followed. Renal transplant was considered to be the final therapeutic modality.
      After gradual recovery, a successful live-related renal transplant was performed.
      As soon as good graft was established, the blood pressure settled and 4 of the 5
      antihypertensives were withdrawn. After 2 weeks, patient was discharged in a
      stable condition with a total stay of about 2 months.

PMID- 17553330
TI  - Creutzfeldt-Jakob disease.
AB  - Creutzfeldt-Jakob disease is a prion related disease, characterized by rapidly
      progressive dementia, associated with myoclonus and ataxia. A 55-year-old male,
      who initially developed depressive symptoms and obsessive-compulsive disorder one
      year before presentation, and in due course, developed ataxia, forgetfulness and
      disorientation in time and space followed by myoclonic jerks with increasing
      difficulty in walking, finally becoming bed bound and developing startle response
      to sound and touch, presented in mute and bed bound state. On the basis of
      typical clinical syndrome, suggestive electroencephalography and magnetic
      resonance imaging, and absence of any other cause, diagnosis of Creutzfeldt-Jakob
      disease was made.

PMID- 17553331
TI  - Three pregnancies with mechanical heart valve and no follow-up in 10 years.
AB  - Anticoagulation and proper INR (International Normalized Ratio) monitoring is
      essential for patients having mechanical heart valves; it is vital in these
      patients in order to prevent lethal complications such as valve thrombosis and
      systemic embolism. In pregnancy, it becomes even more important as pregnancy
      itself is a hypercoagulable state. This report describes a female patient having
      undergone mitral valve replacement with a Starr Edward metallic prosthesis. She
      came back to the operating surgeon after 10 years of valve replacement with a
      history of three uneventful healthy deliveries and no follow-up and INR
      monitoring during this period.

PMID- 17553332
TI  - Biphasic resection of a mandibular molar.
AB  - Teeth once designated obsolete for rehabilitation and deemed for extraction
      should be re-evaluated for salvaging two thirds or even one-third component of
      the individual teeth. In our part of the continent, financial restraints can
      effect the orthodox procedures of root amputation if the final restoration is not
      provided at an earlier date. This case report enlightens on a biphasic approach
      combining radisection and coronal resection of a tooth with an endodontic
      perforation, which is a procedure not normally executed for mandibular molars but
      was adopted after taking the socioeconomic status of the patient into
      consideration.

PMID- 17553333
TI  - Solitary infantile myofibromatosis of the skull.
AB  - This is the report of a 6 months old boy presenting with a firm, solitary mass on
      the temporal region, associated with lysis of local bone. Investigations lead to
      a diagnosis of infantile myofibromatosis (IM). Wide local excision was performed.
      At one year follow-up, no recurrence was noted.

PMID- 17553334
TI  - Blaschkolinear dermatoses--an overview of interesting patterned dermatological
      disorders.
AB  - A large number of congenital/nevoid and acquired skin diseases on the human skin
      and mucosae assume a characteristic morphological pattern following the Blaschko
      lines. This pattern recognition is important for dermatologists so as to have an
      idea about the etiopathogenesis as well as to categorize various such disorders.
      This article is an attempt to overview and classify a variety of blaschkoid
      disorders described so far in the literature.

PMID- 17553335
TI  - Radiofrequency thermal ablation: imaging guided therapeutic applications.
AB  - Minimally invasive, image guided radiofrequency ablation RFA now provides an
      effective local treatment of isolated or localized neoplastic diseases, and is
      also being used as an adjunct to conventional surgery, systemic chemotherapy or
      radiation. It is now the front line treatment in unresectable hepatocellular
      carcinoma and its use in other neoplastic diseases continues to expand. This
      update introduces the technique to alleviate inoperable tumours and application
      of RFA in therapeutic imaging.

PMID- 17553336
TI  - Issues and challenges in expanded programme on immunization in Sindh, Pakistan.

PMID- 17553337
TI  - Chromosomal analysis in epilepsy.

PMID- 17553338
TI  - The toe tourniquet syndrome.

PMID- 17553339
TI  - [Correlation between CD154 (CD40L) expression and naive/memory CD4(+) T cells].
AB  - AIM: To investigate the correlation between CD154(+) T cells, naive/memory CD4(+)
      T cell markers and cytokine expression. METHODS: PBMC from normal persons were
      isolated, stained by fluorescence-conjugated monoclonal antibodies of surface
      markers, intracellular cytokines and CD154, and analyzed at the single cell level
      by flow cytometer. RESULTS: After stimulated in vitro for six hours, CD154 were
      expressed on CD4(+) T cells, rather than on CD8(+) T cells. Analysis of the
      expression of CD45RA (marker for naive T cells) and CD45RO (marker for memory T
      cells) on CD154(+) T cells indicated that the majority of CD4(+) CD154(+) T cells
      were memory T cells. When stimulated by anti CD3 or anti CD3+anti CD28, the cells
      that produced IFN-gamma, IL-2 and TNF-alpha were CD4(+) CD154(+) and a single
      cell produced several cytokines simultaneously. In addition, CD4(+) CD154(+) T
      cells had low level or no expression of CD25 and they didn't express CD62L, but
      approximately fifty percent of the cells expressed CCR7. CONCLUSION: After
      stimulated in vitro for a short time and through further phenotypic and cytokine
      analysis, CD154, together with other cell surface markers and cytokines, can be
      used to discriminate between naive and memory CD4(+) T cells.

PMID- 17553340
TI  - [Discovery of rat Islet-1 gene variant and its expression in NSC].
AB  - AIM: To construct rat Islet-1 gene recombinant retroviral expression vector and
      to transduce Islet-1 gene into neural stem cell (NSC) by the vector. METHODS: The
      cDNA encoding the rat Islet-1 gene was isolated by RT-PCR method, the amplified
      gene fragment was subcloned into the retroviral vector plEGFP-C1. Islet-1 gene
      was transduced into NSC by PA317 packaging cells, then the expression of Islet-1
      in NSC was observed. RESULTS: The recombinant Islet-1 retroviral vector was
      constructed successfully, as shown by PCR, restriction enzymes digestion and
      fluorescence detection, and the positive expression of Islet-1 was found in NSC
      by immunocytochemical staining. The variant of Islet-1 gene was also discovered
      in this study. CONCLUSION: The rat Islet-1 recombinant retroviral vector has been
      successfully prepared, which can be used to study the function of Islet-1 gene in
      NSC differentiation into cholinergic neurons.

PMID- 17553341
TI  - [The effect of interleukin-10 on neurocyte apoptosis in cerebral ischemia in
      rats].
AB  - AIM: To investigate the effect of interleukin-10 on neurocyte apoptosis in
      cerebral ischemia in rats. METHODS: 36 adult male Sprague-Dawley rats were
      randomly assigned into 3 groups: sham operation group, middle cerebral artery
      occlusion(MCAO) group and MCAO+interleukin-10 treatment group. Terminal
      deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling (TUNEL)
      staining was used to detect in situ cell apoptosis, immunohistochemical staining
      and RT-PCR were used to detect the expression of proapoptotic gene Fas, Fas
      ligand (FasL) and caspase-3 in peri-infarct, respectively. RESULTS: Cerebral
      ischemia significantly induced neurocyte apoptosis and upregulated the expression
      of Fas, FasL and caspase-3, repcetively (P<0.05). IL-10 treatment significantly
      inhibited neurocyte apoptosis, and suppressed the expression of proapoptotic gene
      FasL and caspase-3, repcetively (P<0.05), but had no obvious effect on Fas
      expression (P>0.05). CONCLUSION: IL-10 can suppress neurocyte apoptosis in
      cerebral ischemia, whose mechanisms seemed related to inhibiting the expression
      of proapoptotic gene FasL and caspase-3.

PMID- 17553342
TI  - [Establishment of human acute monocytic leukemia model in severe combined
      immunodeficient (SCID) mice and the analysis of pathological changes].
AB  - AIM: To establish a model of human M5 leukemia and investigate the
      pathomorphological change in severe combined immunodeficient (SCID) mice after
      being transplanted with SHI-1 cells. METHODS: Various dose of SHI-1 cells were
      transplanted i.p. into SCID mice. Serial tail vein samples at regular intervals
      were prepared for detecting the expression of CD14, CD137L on SHI-1 cells by flow
      cytometry (FCM). All dying mice were dissectted and the liver, spleen, kidney and
      bone marrow were examined to detect the appearance and distribution of the SHI-1
      cells by FCM and/or immunohistochemistry. RESULTS: Tumors appeared in the
      abdomenion of the mice treated with various dose of SHI-1 cells. However, the
      dissemination of SHI-1 cells in murine tissues was found only in the groups of
      middle/high dose. SHI-1 cells were firstly found in tail vein samples 3 weeks
      after transplantation, and the time of engraftment was related to the dose of
      cells. CONCLUSION: The SHI-1/SCID mice was constructed, which provided a useful
      tool to investigate acute monocytic leukemia(AML).

PMID- 17553343
TI  - [Differential expression of USP2, USP14 and UBE4A between ovarian serous
      cystadenocarcinoma and adjacent normal tissues].
AB  - AIM: The differential expression of USP2, USP14 and UBE4A between ovarian serous
      cystadenocarcinoma and adjacent normal tissues was investigated. METHODS:
      Restriction fragment differential display polymerase chain reaction (RFDD-PCR),
      semi-quantitative RT-PCR and immunohistochemical staining were applied to analyze
      the differentially expressed genes and proteins of ubiquitin specific proteases
      (USPs), USP2 and USP14, and ubiquitin factor E4A (UBE4A) between ovarian serous
      cystadenocarcinoma and adjacent normal tissues obtained from 40 patients aged
      from 29 to 72 years old, collected in 2005 year at excision of surgical operation
      with ovarian serous cystadenocarcinoma. RESULTS: USP2, USP14 and UBE4A were over
      expressed (>3 folds) in ovarian serous cystadenocarcinoma tissues compared to
      normal tissues. CONCLUSION: The results suggest that the activity of ubiquitin
      proteasome system is obviously enhanced in ovarian cancer.

PMID- 17553344
TI  - [Anti-tumor mechanisms of Sp2/0 tumor vaccine transfected with mIL-21 gene in
      mice].
AB  - AIM: To explore the anti-tumor mechanism of Sp2/0-mIL-21 tumor vaccine in mice.
      METHODS: The molecules of MHC-I and CD80 on the surface of Sp2/0-mIL-21 tumor
      vaccine were detected by flow cytometry (FCM) respectively. A flow cytometric
      CFSE-7-AAD cytotoxicity assay was used to detect the cytotoxic activities of NK
      cells and CTLs. The expression of I-TAC in the tumor tissue was tested by RT-PCR.
      RESULTS: The expression of MHC-I molecule on the surface of tumor vaccine was up
      regulated obviously. The cytotoxic activities of NK cells and CTLs were
      significantly enhanced in the mice inoculated with Sp2/0-mIL-21 tumor vaccine
      compared with the mice inoculated with Sp2/0 tumor cell in control group. The
      expression of I-TAC in the tumor tissue was up-regulated. The histopathologic
      section analysis showed more lymphocytes were infiltrated in the tumor tissue.
      CONCLUSION: Sp2/0-mIL-21 tumor vaccine can induce strong cell-mediated immune
      response to tumor cells after it was inoculated s.c into mice. The anti-tumor
      mechanisms induced by Sp2/0 tumor cell vaccine are associated with the
      proliferation and activation of T lymphocyte, the differentiation and maturity of
      NK cell, the infiltration of lymphocytes in tumor tissue, and the enharuement of
      cytotoxic activities of NK cells and CTLs.

PMID- 17553345
TI  - [Construction and expression of eukaryotic expression vector of human 4-1BB
      ligand gene in tumor cells and its antitumor activity in vitro].
AB  - AIM: To construct eukaryotic expression vector of human 4-1BB ligand (4-1BBL)
      gene and express it in HT-29 cell line. To explore the effect on activation and
      cytotoxicity of human cytotoxic T lymphocytes(CTLs) induced by human 4-1BBL gene
      transfection into tumor cells in vitro. METHODS: RT-PCR was applied to amplify
      the full-length of human 4-1BBL gene from Raji cells. After sequencing, the cDNA
      was recombinated into the eukaryotic expression vector pcDNA3.1(-) and
      transfected into HT-29 cells through Lipofect AMINE 2000. Human 4-1BBL mRNA and
      protein expression of transfected cells was detected by RT-PCR and FACS
      respectively. Human peripheral blood mononuclear cells were stimulated with anti
      CD3 mAb and incubated with non-transfected or transfected HT-29 cells,
      respectively. The MTT colorimetry was used to detect the proliferation and
      cytotoxic effect of T lymphocytes. Meanwhile, the expression of intracellular IFN
      gamma was detected by FCM. RESULTS: The HT-29 cells transfected by pcDNA3.1(-)-h4
      1BBL could express human 4-1BBL efficiently. As compared with wild type HT-29
      cells, the transfected HT-29 cells had more effect for proliferation, IFN-gamma
      production and cytotoxic activity of lymphocytes. CONCLUSION: The recombinant
      eukaryotic expression vector of pcDNA3.1(-)-h4-1BBL is successfully constructed.
      The transfection of human 4-1BBL gene in HT-29 cells is effctive in enhancing its
      immunogenicity and inducing antitumor immune response in vitro.

PMID- 17553346
TI  - [Expression and characterization of human sTNFR II-IgG Fc fusion protein in
      Pichia pastoris].
AB  - AIM: To find if human soluble tumor necrosis factor receptor II (p75) fused IgG
      Fc protein (sTNFR II-IgG Fc) could be expressed in Pichia pastoris with an active
      dimmer form and characterize its N-linked oligosaccharides. METHODS: Two gene
      fragment, human sTNFR II and IgGFc, were got by RT-PCR from leucocytes stimulated
      with LPS. And the chimeric gene sTNFR II-IgG Fc achieved through gene splicing by
      over lap extension (SOE) method was cloned into pPIC9 and transformed into
      methanotropic yeast Pichia pastoris. The fusion protein purified by Protein A
      affinity column was analyzed with SDS-PAGE electrophoresis under reducing or non
      reducing conditions and immunological methods. The anti-TNF-alpha biological
      activity assay of fusion protein was performed with L929 cells and detected with
      MTT colorimetry. The N-linked oligosaccharides hydrolyzed from fusion protein
      were labeled with 8-amino-1, 3, 6-naphthalene trisulfonic acid (ANTS) were
      analyzed with fluorophore-assisted carbohydrate eletrophoresis (FACE) as well.
      RESULTS: The recombinant P. pastoris strain that expressed human sTNFR II-IgG Fc
      fusion protein was constructed. The expression level of fusion protein in 2 L
      flask reached 2 mg/L. SDS-PAGE and Western blot showed the expressed fusion
      protein purified by protein was a dimer linked with inter-molecular disulfide
      linkage. The fusion protein neutralized cytotoxic activity of TNF-alpha to L929
      cells, and the EC(50) of the fusion protein to inhibit 5 x 10(4) U/L of TNF-alpha
      was 170 microg/L. The FACE analysis showed there are 11 to 13 hexoses on each N
      linked oligosaccharide. CONCLUSION: The human sTNFR II-IgG Fc fusion protein is
      expressed successfully in P. pastoris and it could be a reference for the future
      expression of other Fc fusion proteins or immunoglobulins in Pichia pastoris.

PMID- 17553347
TI  - [Relationship between iceA1, iceA2 and babA2 genes of Hp in Xi'an and
      gastroduodenal diseases].
AB  - AIM: To investigate the distribution of iceA1, iceA2 and babA2 genes of
      helicobacter pylori (Hp) in Xi'an and analyse the relationship between these
      genes and gastroduodenal diseases. METHODS: 88 Hp strains were isolated from the
      patients with different gastric duodenal diseases. After genomic DNA was
      extracted, iceA1, iceA2 and babA2 genotypes of Hp were determined by polymerase
      chain reaction (PCR). The results were analyzed statistically by chi(2) test.
      RESULTS: 88 Hp strains were detected from 163 samples and the detection rate was
      54%. The positive rate of iceA1, iceA2 and babA2 of the 88 Hp strains was 76.1%,
      21.6% and 25%, respectively. These genotypes showed no statistical difference in
      the distribution of different gastric duodenal diseases (P>0.05). CONCLUSION:
      iceA1 of Hp ispredominated in Xi'an area. These genotypes have no correlation
      with the clinical outcome of Hp infection.

PMID- 17553348
TI  - [Study on the expression of TLR4 on splenocytes and its relation with CD4(+)
      CD25(+) regulatory T cells in peripheral blood in severely burnt rats].
AB  - AIM: To investigate the expression of Toll like receptor 4(TLR4) on splenocytes
      and TNF-alpha mRNA, the dynamic changes of CD4(+) CD25(+) regulatory T cell(Treg)
      and endotoxin(ET) in peripheral blood of burnt rats during the early phase, and
      to explore the mechanism against inflammatory reaction in intestine-derived
      infection after burn. METHODS: 64 SD male rats were randomly separated into
      control group and burn model groups. Rats of burn model group were burnt with
      vapor under 3 mPa pressure and 108 degrees Celsius temperature for 8 seconds to
      achieve deep partial-thickness burn, and a 30% total body surface area (TBSA)
      burn model was made. Rats were sacrificed before and 2, 5, 8, 12, 24, 48 and 72 h
      after burn, and the TLR4 and TNF-alpha mRNA expression in splenocytes were
      measured at various intervals by RT-PCR. The expression of TLR4 protein was
      measured by Western blot, and the percentage of Treg cells in CD4(+) T cells was
      detected by flow cytometry (FCM), and the LPS concentration of plasma was
      detected by limulus lysate test. RESULTS: The expression of TLR4 mRNA, TNF-alpha
      mRNA, TLR4 protein and the levels of Treg, ET were significantly increased at
      some times points after burn. The expression of TLR4 mRNA and protein reached the
      peak at 8 h, whereas the TNF-alpha mRNA at 12 h, and Treg and ET at 8 h. The peak
      values of them were 3.66+/-0.51, 2.27+/-0.19, 1.65+/-0.23, 63.19+/-12.65% and
      11.68+/-1.71 Eu/mL respectively, which were of significant difference when
      compared with the control group (P<0.01). The expression of TLR4 mRNA showed a
      positive correlation with that of Treg, ET and TNF-alpha mRNA (r=0.898, 0.811,
      0.462, P<0.01). CONCLUSION: Treg might play a major role in the process of immune
      regulation in rats after burn, the mechanism of which may be correlated with the
      increase of LPS-TLR4 signal transduced by intestine-derived infection.

PMID- 17553349
TI  - [Paharmacological mechanisms of cellular immunity of overall alkali of tongbiling
      for the treatment of joint destruction].
AB  - AIM: To investigate the effect of the overall alkali of Traditional Chinese
      Medicine tongbiling(TBL) which comprises brucine and strychnine alkaloids on
      collagen induced-arthritis(CIA) and study its paharmacological mechanisms of
      cellular immunity. METHODS: Bovine CII was emulsified in Freund's incomplete
      adjuvant. Wistar rats were injected with Type II collagen intradermally at the
      base of the tail. After swelling, CIA groups were, randomly divided into
      physiological saline group and treatment group. Then the swelling of the rats'
      hindlimbs was evaluated. The whole body of the rats treated on 35 th days was
      photographed by mammography X-Ray. 96 joints in erosion scoring system and 100
      joints in joint spacing narrow(JSN) scoring system were used to observe the joint
      destruction of CIA from X-Ray comprehensively and objectively. After the rats
      were killed, the third proximal claw pad of the right hindlimb and left forelimb
      were stained by HE dying, Neutrophil, lymphocyte, plasmacyte infiltration and
      hyperplasia of synoviocytes were assessed. Then MTT and Western blot were used to
      determine the effect of the overall alkali of TBL on proliferation of Jurkat
      cells and ERK1/2 phosphorylation of Jurkat cells, respectively. RESULTS:
      Inflammation of CIA joints was aggravated quickly. The swelling of CIA rats
      treated by MTX and overall alkali of TBL for 35 days was relieved (P<0.05). MTX
      and overall alkali of TBL inhibited the hyperplasia of synoviocytes. Overall
      alkali of TBL inhibited the infiltration of lymphocyteS and plasmacytes. Overall
      alkali of TBL inhibited the proliferation and ERK1/2 phosphorylation of Jurkat
      cells. CONCLUSION: Overall alkali of TBL could relieve joint inflammation and
      destruction of CIA rats by blocking the MAPK cell signalling pathway to inhibit
      the activation and proliferation of T cells. Our study might provide an
      experimental basis for treatment of rheumatoid arthritis with overall alkali of
      TBL.

PMID- 17553350
TI  - [Changes of the content of Se and the levels of several cytokines in the serum of
      patients with Kaschin-Beck disease].
AB  - AIM: To investigate the levels of selenium (Se) and several cytokines (TNF-alpha,
      VEGF and IL-1beta) in the serum of patients with Kaschin-Beck disease (KBD).
      METHODS: 90 subjects were selected, from KBD areas and non-KBD areas of Lhasa,
      Tibet. Then they were divided into 3 groups: the group with KBD (30), the control
      in KBD areas (30), and the control in non-KBD areas (30). There was no obvious
      difference in sex and age in the three groups. The content of Se in the serum was
      detected by atomic fluorescent spectrometer and the level of cytokines (TNF
      alpha, VEGF and IL-1beta) in the serum were detected by ELISA. RESULTS: The
      content of Se in the serum of persons living in the KBD-disease areas were lower
      than that of persons living in non-KBD disease areas. The levels of TNF-alpha,
      VEGF and IL-beta in KBD group were higher than those in normal control group
      (P<0.05). The content of Se had negative correlation with the levels of TNF-alpha
      and IL-beta in serum. CONCLUSION: The decrease of Se content and increase of the
      levels of TNF-alpha, VEGF and IL-1beta may play a role in pathogenesis of KBD.

PMID- 17553351
TI  - [Different responses of CD94/NKG2A-bright and CD94/NKG2A-dim NK cell subsets
      isolated from patients with multiple sclerosis to interferon-beta].
AB  - AIM: To analyze the different responses of NK cell subsets isolated from the
      patients with proceeding multiple sclerosis to interferon-beta. METHODS: NK cells
      were isolated from the patients' peripheral blood mononuclear cells, separated
      into two subsets: CD94/NKG2A-bright and CD94/NKG2A-dim and then sorted by flow
      cytometry. The two subsets were cultured with IFN-beta to evaluate CD94/NKG2A
      expression pattern and the corresponding cell proliferation and secreted IL-10
      and TGF-beta. RESULTS: The positive NK cells of CD94/NKG2A made up 25.5% within
      the whole NK population. Among them, CD94/NKG2A-bright and CD94/NKG2A-dim
      amounted to 23.6% and 76.4%, respectively. When INF-beta was added to two groups,
      the proliferation rate of CD94/NKG2A-bright group was much lower than that of
      CD94/NKG2A-dim group and its expression pattern didn't alter greatly. In
      contrast, the expression of CD94/NKG2A in CD94/NKG2A-dim group was markedly
      increased. IL-10 and TGF-beta secretion was increased dominantly compared with
      the two untreated groups. There were great differences between the secreted IL-10
      and TGF-beta in the stimulated groups. CONCLUSION: IFN-beta can inhibit NK cells
      by inducing the inhibitory expression of CD94/NKG2A and stimulate IL-10 and TGF
      beta secretion. CD94/NKG2A-bright group and CD94/NKG2A-dim group make different
      reaction to IFN-beta.

PMID- 17553352
TI  - [The role of IFN-gamma, IL-10, IL-12 and TRAIL in sera and synovium fluids from
      patients with rheumatoid arthritis].
AB  - AIM: To study on the role of IFN-gamma, IL-10, IL-12 and TRAIL in the
      pathogenesis of RA. METHODS: The concentrations of IFN-gamma, IL-12, IL-10 and
      TRAIL in synovium fluid and sera isolated from 46 patients with RA were
      determined by Sandwich ELISA. RESULTS: The concentrations (ng/L) of IFN-gamma, IL
      12 and TRAIL in synovium fluids from the patients were (106.2+/-7.8), (57.7+/
      3.5) and (166.5+/-12.3), respectively. The concentrations (ng/L) of these
      cytokines in sera from the patients were (56.3+/-7.4), (35.1+/-12.7), (69.5+/
      8.3) and in sera from the healthy donors (31.1+/-4.4), (25.2+/-2.6) and (41.2+/
      4.8). The levels of cytokines mentioned above in synovium fluid from the patients
      were higher than those in sera from both the patients and the healthy individuals
      (P<0.05, P<0.01). There was no significant difference of concentration of IL-10
      between the patients and the healthy donors. CONCLUSION: The levels of IFN-gamma,
      IL-12 and TRAIL in synovium fluid from the patients with RA are higher than those
      in healthy donors. This result indicates that the pattern of cytokine on course
      of RA is main of Th1, more typical in synovium fluid than in serum. Analysis of
      the concentration of IFN-gamma, IL-12, IL-10 and TRAIL in the serum may be useful
      to diagnosis and bio-immunological treatment of the RA patients correctly.

PMID- 17553353
TI  - [Preparation, characterization and preliminary application of monoclonal antibody
      against the transpeptidase domain of MRSA-PBP2a].
AB  - AIM: To prepare monoclonal antibody (mAb) against the penicillin binding protein
      2a (PBP2a) of MRSA and establish a latex agglutination assay to detect PBP2a.
      METHODS: BALB/c mice were immunized with the recombinant transpeptidase domain of
      PBP2a expressed by gene-engineering. Mouse mAb against PBP2a was obtained with
      hybridoma technique. mAb's characteristics (IgG subclasses, titers,
      specificities, and affinities) were identified and determined by indirect ELISA
      and Western blot. Polystyrene beads were sensitized with mAb F2 by physical
      adsorption, and a latex agglutination assay was developed to detect PBP2a.
      RESULTS: Two strains of hybridoma cell lines, which could stably secret anti
      PBP2a mAb were obtained, named F1 and F2. The isotype of F1 and F2 was both IgG1.
      Ascites titers were 0.5x10(-6)-1x10(-6) and the affinity constants (Kaff) were
      1.57 x 10(8) M(-1) and 5.43 x 10(9) M(-1), respectively. Western blot analysis
      showed that both the mAbs had specific binding abilities with both recombinant
      protein and clinically isolated MRSA-PBP2a. The sensitivity of the anti-PBP2a
      latex agglutination assay with serial dilutions of purified PBP2a was found to be
      1 mg/L. CONCLUSION: The obtained two strains of hybridoma cell lines can secret
      anti-PBP2a mAb stably, which lays the foundation for establishment of a simple
      and rapid anti-PBP2a latex agglutination assay kit.

PMID- 17553354
TI  - [Preparation and identification of monoclonal antibodies against Type M/N and
      Glycophorin A/B].
AB  - AIM: To prepare monoclonal antibodies(mAbs) against Type M/N and monoclonal
      antibodies against Glycophorin A and Glycophorin B (GPA/GPB) and identify rare
      blood group MkMk. METHODS: 8 week-old female BALB/c mice were immunized with type
      "O" red blood cells, Splenocytes from the immunized mice were fused with Sp2/0
      myeloma cells, and positive hybridoma clones were screened by panel erythrocytes.
      The titer of supernatant and ascitic fluid was tested by direct and indirect
      agglutination. The subclasses and isotypes were identified by monoclonal antibody
      isotyping kit. The complemental structures of the combining sites of their
      antibody antigen were determined by enzyme-treated red cells. The specificity of
      the GPA/GPB mAbs was identified by Western blot analysis. RESULTS: Eight
      hybridoma cell lines against Type M/N and GPA/GPB were obtained. The titer of
      supernatant was between 1 x 2(-4) - 1 x 2(-8), and the titer of ascitic fluid was
      between 1 x 2(-7) - 1 x 2(-12). The immunoglobulin subclasses of all the mAbs
      were IgG except 1C1C9C4, which was IgM. Four anti-M mAbs and one anti-N mAb were
      deterimined by agglutination test using panel erythrocytes and the test of the
      combining sites in antiody antigen. Western blot analysis proved that three mAbs
      recognized GPA/GPB protein. CONCLUSION: Eight hybridoma cell lines against Type
      M/N and GPA/GPB have been obtained successfully. Among them, four mAbs recognize
      M, one recognizes N and three recognize GPA/GPB. Our study may be useful to
      research into MN blood group and for serological diagnosis. The anti-GPA/GPB mAbs
      can be used to prepare diabodies for the treatment and diagnosis of some of
      diseases.

PMID- 17553355
TI  - [Mechanism of the effect of LPSp on the production of anti-HBs in mice].
AB  - AIM: To investigate the mechanism of the effect of avirulent Pantoea agglomerans
      lipopolysaccharide (LPSp) as the adjuvant of HBsAg on the production of anti-HBs
      in mice. METHODS: The peritoneal macrophages of BALB/c mice were pulsed in vitro
      by HBsAg+LPSp, HBsAg, LPSp, and NS respectively. The levels of anti-HBs IgG in
      serum were determined by ELISA. The variation of phagocytosis of the macrophages
      was detected. The culture supernatants were harvested and assayed for TNF-alpha
      and NO. HBsAg-pulsed peritoneal macrophages in the presence or absence of LPSp
      were injected in the hind footpads of syngeneic mice. Lymph node cells were
      harvested and cultured by HBsAg. IL-4 and IFN-gamma in the supernatants were
      quantitated by ELISA. RESULTS: The titer of anti-HBs IgG from the mice immunized
      with HBsAg-pulsed peritoneal macrophages treated with LPSp was higher than that
      of the mice immunized in the absence of LPSp. The phagocytosis rate of the LPSp
      treated peritoneal macrophages was higher than that of the untreated macrophages.
      The level of TNF-alpha and NO of the LPSp-treated peritoneal macrophages was
      higher than that of the untreated macrophages. HBsAg-pulsed peritoneal cells in
      the presence of LPSp can induced higher production of IL-4 than those in the
      absence of LPSp. CONCLUSION: LPSp can act as the adjuvant of HBsAg and
      effectively increase the anti-HBS in the mice immunized by HBsAg. LPSp can
      activate macrophages and stimulate HBsAg-pulsed macrophages to induce the
      production of IL-4 of lymph node cells.

PMID- 17553356
TI  - [Prokaryotic expression and immunogenicity of hWAPL, a norel oncogene related to
      cervical cancer].
AB  - AIM: To construct the prokaryotic expression plasmid of hWAPL, induce the
      expression of the protein and prepare polyclonal antibody. METHODS: The hWAPL
      cDNA was amplified by RT-PCR from HeLa cells derived RNA and then cloned to pMD18
      T according to A-T. The DNA fragment was isolated and linked to prokaryotic
      expression vector pET28a. The recombinant protein was induced by IPTG and
      identified by SDS-PAGE. Then it was injected into mice to prepare polyclonal
      antibody. The immunogenicity and specificity of the recombinant protein were
      identified by ELISA and Western blot. RESULTS: The sequencing, PCR and
      endonucleases digestion results showed that the hWAPL fragment was correctly
      inserted into pMD18-T and pET28a vectors. SDS-PAGE showed 25,000 fusion hWAPL
      protein was expressed in BL21 cells. The titer of polyclonal antibody was 1:3 200
      by indirect ELISA. The 25,000 fusion hWAPL protein was detected by SDS-PAGE and
      Western blot. CONCLUSION: The hWAPL protein can be expressed by prokaryotic
      vector pET28a. Furthermore, the expression protein can be used as immunogen to
      generate antibodies with specificity.

PMID- 17553357
TI  - [Expression of human-mouse chimeric antibody against CD40 in CHO cell line and
      characterization of its function].
AB  - AIM: To investigate the stable expression of a chimeric antibody against CD40
      moleculeech-5C11ein CHO and its biological activity. METHODS: Human-mouse
      chimeric antibody against CD40 recombinant plasmid and mock plasmid were
      transfected into CHO cell line through lipofectamine mediation. Human kappa chain
      and Fc fragment of ch-5C11 were characterized by FACS and Western blot. The
      concentration of ch-5C11 in cell supernatants was detected by Lowry assay and the
      inhibitory effect of ch-5C11 on the proliferation of Daudi cells was detected by
      MTT assay. RESULTS: RT-PCR showed that target CHO cells integrated chimeric heavy
      chain and chimeric light chain gene. FACS and Western blot showed that ch-5C11 in
      cell supernatants maintained the binding activity and specificity to human CD40
      molecule, and contained human kappa chain and Fc fragment. Cell supernatants were
      purified using protein G affinity chromatography. The concentration of human
      mouse chimeric antibody against CD40 in cell supernatants was 0.535 mg/L. When co
      cultured with B lymphoma cell line Daudi, ch-5C11 induced proliferation arrest of
      Daudi cells. CONCLUSION: The human-mouse chimeric antibody against CD40 can be
      expressed in CHO stably and effectively, which inhibits proliferation of Daudi.

PMID- 17553358
TI  - [Application of multiple antigen peptide immunomagnetic beads in single-epitope
      antibody preparation].
AB  - AIM: To prepare specific single-epitope antibody using immunomagnetic beads
      coated with multiple antigen peptides(MAP). METHODS: Eight-branch MAP is
      synthesized by Fmoc SPPS. After immunizing the BALB/c mice with the MAP,
      polyclonal antiserum was obtained. Then, the immunomagnetic beads (IB) were
      prepared by coating with the MAP in covalent bond form and were used to purify
      the specific single-epitope antibody from the antiserum of immunized animals.
      RESULTS: The titer of antiserum was 1:12,800, which showed the strong
      immunogenicity of MAP. The best coating concentration of MAP was 100 mg/L and the
      max coating efficiency was 79%. After purifying specific antibody from polyclonal
      antiserum using the IB, the obtained antibodies only interacted with one epitope
      rather than other epitopes. The purity of the antibody reached 95% and the mean
      recovery rate was 5.8%. CONCLUSION: The beads coated with MAP can be used to
      quickly isolate specific single-epitope antibody which is similar to monoclonal
      antibody. This method provide a convenient shortcut in preparing small amount of
      antibody with high specificity.

PMID- 17553359
TI  - [EPO mediated proliferation and differentiation of human erythroid progenitor
      inhibited by FK228].
AB  - AIM: To investigate the function of histone deacetylases (HDACs) inhibitor FK228
      in the EPO mediated proliferation and differentiation of human erythroid
      progenitor. METHODS: CD34(+) cells were separated from the granulocyte colony
      stimulating factor-mobilized peripheral blood of patients with cancer. They were
      cultured for 7 days with serum-free medium containing stem cell factor (SCF),
      erythropoietin (EPO) or SCF+IL-3 in the presence of escalated dosages of FK228.
      After immunofluorescent staining with anti-GPA-PE and anti-CD36-FITC, cell count
      and Flow cytometric analysis were performed; CD34(+) cells were cultured for 7
      days with serum-free medium containing SCF+IL-3 and enriched for CD36(+) GPA(-)
      cells, which were cultured for 7 days with serum-free medium containing
      EPO+FK228. Then the cell count was conducted. CD36(+) GPA(-) cells were cultured
      for 7 days with serum-free medium containing EPO in the presence or absence of
      FK228 and then they were stained with annexin V and PI. RESULTS: FK228 inhibited
      the generation of CD36(+) GPA(high), CD36(+) GPA(low) and CD36(+) GPA(-) cells in
      a dosage-dependent manner. FK228 induced the apoptosis of CD36(+) GPA(high) and
      CD36(+) GPA(low/-) cells in the presence of EPO. CONCLUSION: FK228 can inhibit
      the EPO mediated proliferation and differentiation of human erythroid progenitor.

PMID- 17553360
TI  - [The prince on the chestnut].

PMID- 17553361
TI  - [Prostate cancer--incidence and risk factors].
AB  - Although prostate cancer is among the most common male cancers, little
      information is available on risk factors. The paper reviews trends in prostate
      cancer incidence, and possible risk factors are discussed. Incidence appears to
      have peaked and is predicted to stabilize at a higher level due to screening.
      Besides heredity, epidemiological studies on prostate cancer produce equivocal
      results. Lifestyle and environment are likely to have an important impact on
      prostate cancer risk, but significant and clinically relevant risk factors have
      yet to be identified.

PMID- 17553362
TI  - [Screening for prostate cancer--what does the evidence show?].
AB  - A recent Cochrane review of the available randomised evidence for screening for
      prostate cancer is referred and discussed. The review concludes that there is
      insufficient evidence to either support or refute the routine use of mass,
      selective or opportunistic screening compared to no screening in order to reduce
      prostate cancer mortality. Until ongoing large, randomised screening trials
      mature and produce results that may prove otherwise, the Danish policy of not
      recommending PSA-based screening should be upheld.

PMID- 17553363
TI  - [Diagnosis, evaluation and follow-up of patients with prostatic cancer].
AB  - The current diagnostic modalities for diagnosing and evaluating prostate cancer
      are described. DRE, PSA and TRUS are the three major cornerstones of the
      diagnostic approach and further evaluation includes bone scans. Lymphnode status
      can be evaluated only by lymphadenectomy, but is only of interest when curative
      treatment is considered. Follow-up after both curative intended treatment and
      hormonal treatment for advanced disease includes regular clinical checkups and
      evaluation of PSA status. Specific examinations may be considered depending on
      the symptoms and findings.

PMID- 17553364
TI  - [Medical treatment of voiding problems in men].
AB  - Lower Urinary Tract Symptoms (LUTS) e.g. in prostatic infravesical obstruction
      and symptoms of overactive bladder (OAB) in men can be treated effectively with
      drugs. The current evidence for use of alpha-adrenergic blocking agents, 5-alpha
      reductase inhibitors, combination therapy and antimuscarinic agents is reviewed
      with suggestions for follow-up. The increasing use of alpha-blockers, 5-alpha
      reductase inhibitors, or both for symptomatic BPH has led to a significant
      decrease in the number of operations for BPH in the last decade. Bothersome
      nocturia due to nocturnal polyuria may be resolved by the administration of a
      loop-diuretic in the late afternoon.

PMID- 17553365
TI  - [Surgical treatment of benign prostatic hypertrophy].
AB  - Transurethral resection of the prostate (TURP) has become the "gold standard"
      although there is risk of postoperative bleeding and TUR syndrome. The main
      advantage of photoselective vaporisation of the prostate (PVP) is minimal
      bleeding; however, long-term results of PVP are pending. Transvesical
      prostatectomy is limited today to large prostates because of the high
      perioperative morbidity. Transurethral microwave therapy (TUMT) has lost some of
      its popularity because of post treatment catherization for several weeks and
      reduced long-term results compared with TURP.

PMID- 17553366
TI  - [Surgical treatment of benign prostatic hyperplasia in Denmark--1993-2003].
AB  - INTRODUCTION: The treatment of BPH includes many possibilities, from medical
      treatment to open prostatectomy. During the last 20 years medical treatment has
      increasingly been used. Furthermore, new minimal invasive techniques have been
      developed. The aim of this study was to examine changes in the surgical treatment
      of BPH from 1993 to 2003. MATERIALS AND METHODS: Data were drawn from the
      National Patient Register and Statistics Denmark from 1993 to 2003. For each
      operation case, the diagnosis, region, age group in decades, and the year of the
      operation were registered. BPH-related cases include prostatic hypertrophia,
      benign prostatic neoplasm, bladder stone, urinary retention, hematuria, LUTS, and
      bladder neck stenosis. RESULTS: In the 10-year period 63,970 prostate operations
      were performed. 44,347 of these operations could be related to BPH. 21% fewer
      prostate operations were performed in 2003 than in 1993. Standard prostate
      operations constituted 93-97% of all operations during the entire period. The
      operation rate per 1,000 men older than 50 years was median 6.5 in 1993 and 4.5
      in 2003. The rate differed considerably between regions. There was a large
      variation in the number of operations per region with the new techniques. The use
      of the new techniques has been constantly low during the entire period.
      CONCLUSION: In 2003 21% fewer prostate operations were performed than in 1993.
      Standard prostate operations constituted more than 90% of operations during the
      entire period. The use of the new techniques has been constantly low.

PMID- 17553367
TI  - [Treatment of localised prostate cancer].
AB  - The incidence of prostate cancer is increasing sharply in Denmark and an
      increasing proportion of patients have clinically localised disease at diagnosis.
      The therapeutic strategy encompasses intended curative therapy: radical
      prostatectomy with complete removal of the prostate gland and seminal vesicles
      performed as an open procedure or laparoscopically, external beam radiation
      therapy, or implantation of radioactive seeds into the prostate (brachytherapy).
      In older patients with good prognostic factors, active surveillance should be
      considered. The various therapeutic modalities are reviewed.

PMID- 17553368
TI  - [Treatment of hormonal refractory metastatic prostate cancer].
AB  - Hormonal refractory metastatic prostate cancer is a fatal disease with a poor
      prognosis. Treatment options are palliative with second line anti-hormonal,
      estrogens and prednisolon. When palliation is the goal, the side effects have to
      be carefully considered. Local radiotherapy has an effective pain relieving
      effect, and can be repeated. Chemotherapy with docetaxel and prednisolon is
      indicated in patients with symptomatic metastatic disease. Newer options with
      immunotherapy and designed molecules have not yet proven effective. Pain and
      anemia are significant symptoms and should be treated in a multidisciplinary
      setting.

PMID- 17553369
TI  - [Rising Prostate Specific Antigen following treatment with curative intention].
AB  - Rising Prostate Specific Antigen (PSA) is the primary and most sensitive sign of
      recurrent disease following treatment with curative intention of local prostate
      cancer. Depending on the treatment modality, a rising PSA should be interpreted
      differently. After radical prostatectomy PSA values exceeding 0.2 Ng/ml are
      considered a true recurrence. Depending on various variables such as the time
      span from operation to PSA recurrence, the PSA velocity, the PSA doubling time,
      etc., local recurrence vs. dissemination of the disease may be predicted.
      Following radiation therapy, PSA values > or = 2.0 Ng/ml over the nadir are
      considered to be true recurrence.

PMID- 17553370
TI  - [Urinary incontinence after prostatic surgery].
AB  - The prevalence of stress urinary incontinence after prostatic surgery for benign
      disease is 0-2% and 5-35% after surgery for malignant disease. After radical
      prostatectomy for prostate cancer spontaneous improvement of stress incontinence
      occurs up to 1 year after surgery. Medical treatment with doloxetine (a
      serotonine-noradrenaline-reuptake inhibitor) and minimal invasive treatments like
      urethral bulking and male sling procedures are only effective against minor
      stress incontinence. Implantation of artificial urethral sphincter prosthesis
      remains gold standard for effective treatment and lasting effect.

PMID- 17553371
TI  - [Development of an Internet search strategy to identify new medical technologies
      in prostate cancer].
AB  - INTRODUCTION: Technological change is rapid in medicine. The Internet is becoming
      more and more important as a source of keeping abreast of technological change,
      but tools to aid clinicians in finding relevant information on the Internet are
      lacking. The objective of this project was to develop an Internet search strategy
      to identify new technologies for the treatment of localised prostate cancer.
      MATERIALS AND METHODS: Web sites were found by means of a literature search and
      by searching specific Internet sources. Inclusion and exclusion criteria were
      developed based on literature and applied to a variety of potentially relevant
      sites. An initial strategy was developed, technologies identified, and the
      novelty and relevance were assessed by urologists in the team. This information
      was used to adjust the strategy. 6 general urologists assessed the efficiency of
      the strategy. Their input was used to define a final listing of sites. RESULTS:
      The strategy consists of 10 sites which should be visited in the following order:
      YahooHealth, DoctorsGuide, The National Electronic Library for Medicines,
      CancerPage, Medscape, MedlinePlus, HealthAndAge, CancerConsultants, EurekAlert,
      Oncolink. Links to the exact sites are provided at www.ugeskriftet.dk.
      CONCLUSION: This study resulted in an Internet search strategy to identify new
      medical technologies for a well-defined indication. The methods used may be
      useful in order to develop similar strategies in other clinical areas in urology
      or other specialties.

PMID- 17553372
TI  - [Radical prostatectomies for localized prostate cancer performed in center
      satellite collaboration--is it possible?].
AB  - INTRODUCTION: In an effort to comply with the increasing demand for surgery for
      localized prostate cancer a center satellite collaboration was established
      between a university department and two local urological departments. The purpose
      of the present study was to evaluate open radical prostatectomies performed by
      this collaboration. MATERIALS AND METHODS: The centre satellite collaboration
      included preoperative evaluation and treatment at local hospitals and evaluation
      of operative results by audit every 6 months. RESULTS: 104 patients were operated
      during the study period. 4 patients were excluded due to findings of carcinoma in
      lymph nodes examined by frozen section. This study describes the first 100
      radical prostatectomies. Median operating time was 85 minutes (60-175) and median
      hospitalization was 6 days (5-23). 18 patients received blood transfusions in
      relation to surgery. Perioperative mortality was 0. Histological examination of
      prostatectomy specimens revealed that 70 patients had a localised prostate cancer
      (organ confined tumour) and were considered cured for their cancer. Few patients
      had full urinary control (no pads) at 6 weeks control, and at 12 months control
      49 of 50 controlled patients were considered continent. Potency was a major
      problem. 22% of the 50 patients evaluated after 12 months had PSA recurrence and
      almost all were given adjuvant hormonal treatment. CONCLUSIONS: Radical
      prostatectomy performed in collaboration between a university department and
      local urological departments as described is beneficial to both patients and the
      departments involved. Postoperative results matching larger departments can be
      achieved.

PMID- 17553373
TI  - [Prostatitis--pelvic pain syndrome].
AB  - Prostatitis is classified according to the National Institute of Health
      Prostatitis Classification. The term Chronic Pelvic Pain Syndrome (CPPS) covers
      the symptomathology and clinical findings. The main symptoms are pain and voiding
      disorders. Acute bacterial prostatitis is only seen in 5% of cases. The vast
      majority of symptoms are found in CPPS, and urodynamic investigation is crucial
      in order to identify bladder neck dysfunction which occurs in a considerable
      number of patients.

PMID- 17553374
TI  - [Investigation of lower urinary tract symptoms among men in general practice and
      in hospitals].
AB  - Many men over 50 years of age have lower urinary tract symptoms (LUTS). It is
      therefore important that evaluation of symptoms and treatment decision is mainly
      taken care of by the family practitioner. A guideline for evaluation of LUTS is
      described, giving the family practitioner an adequate tool for evaluation and
      decision-making. The guidelines also describe which patients should be referred
      to an urologist and the extent of supplementary evaluation that should be
      performed in this setting.

PMID- 17553375
TI  - [Vacuum-assisted closure of the open abdomen].

PMID- 17553376
TI  - [The use of topical negative pressure in an open abdomen].
AB  - The article is a review of the literature concerning the use of topical negative
      pressure (TNP) in open abdomen. TNP appears to be superior to other methods in
      that the frequency of ventral hernia seems to be less after TNP than after other
      methods. TNP reduces both the cost of nursing and the damage to the abdominal
      wall. Vacuum-assisted closure (VAC) appears to be superior to the vacuum pack
      technique, but there is a lack of studies comparing the two methods of TNP in
      open abdomen.

PMID- 17553377
TI  - [Benign paroxysmal positional vertigo--the most common form of otogenic vertigo].
AB  - Benign paroxysmal positional vertigo presents with brief, episodic, positioning
      provoked vertigo and characteristic findings on Dix-Hallpike and other positional
      tests. This article is based on a systematic review of the literature and
      describes epidemiology, etiology, pathogenesis, diagnostic positional tests and
      treatment using canalith repositioning, liberatory and 360 degrees rotation
      manoeuvres. Diagnostic pitfalls, mastoid vibration, postmanoeuvre activity
      restriction and the ideal number of repositioning manoeuvres per treatment
      session are discussed.

PMID- 17553378
TI  - [Personality disorders].
AB  - Most clinicians are very reluctant to diagnose personality disorders. They lack
      clinical experience and need reliable diagnostic tools. Our current knowledge of
      the biological mechanism and the role of childhood experience is still scarce.
      Personality disorders have a better outcome - partly because more evidenced-based
      treatment programmes have become available. Specialized training programmes for
      young researchers as well as educational activities devoted to training all staff
      involved in the treatment of severe personality disorders need to be established.

PMID- 17553379
TI  - [Health examinations in connection with night work].
AB  - Some 10% of the labour force work during night hours. According to an EU
      directive night workers should be offered preventive health examinations. It is
      well known that night work is related to sleep disorders but the epidemiologic
      evidence linking night work with increased occurrence of peptic ulcers, breast
      cancer, cardiovascular disease and spontaneous abortions is still limited and
      provides no strong rationale for preventive health examinations. This article
      argues that individual health examinations should be integrated into primary
      preventive activities at the workplace.

PMID- 17553380
TI  - [The elderly male patient with tendency to accidental falls and memory problems].

PMID- 17553381
TI  - [Centralization on fewer surgeons--an example from gastric surgery].
AB  - INTRODUCTION: Previous studies have shown an association between surgical volume
      and a decreased mortality rate for departments as a whole as well as for
      individual surgeons. The background for this study was to investigate whether it
      would be beneficial to centralize gastric surgery, not only in fewer departments
      but also in fewer hands in the department. MATERIALS AND METHODS: The study was
      based on the patient records of the 93 patients operated between 1 January 2000
      and 1 September 2005. The surgeons were divided into two groups based on whether
      they had performed more than 15 or less than 5 operations during the period.
      RESULTS: Of the 93 operations, 3 surgeons performed 80 and 7 surgeons performed
      the remaining 13 operations. The mortality was significantly increased in
      patients operated by surgeons with a low operation volume, p = 0.0004. The 12
      acute operations were performed as often by a surgeon with low operation volume
      as by a surgeon with high operation volume. Again, mortality increased when the
      operation was performed by a surgeon with low operation volume, p = 0.015.
      CONCLUSION: The results argue for a centralization of gastric resections on a few
      surgeons and for an organisation of acute surgery so that these procedures are
      performed by only a few experienced surgeons.

PMID- 17553382
TI  - [Does generic lamotrigine lead to larger variations in plasma concentrations?].
AB  - INTRODUCTION: As of 1st June 2005 it is possible to market generic epilepsy drugs
      with the active substance lamotrigine because the patent on the original product
      Lamictal had expired. We wanted to investigate if generic lamotrigine leads to
      larger variations in plasma concentrations of lamotrigine. MATERIALS AND METHODS:
      The citizens of the county of Vejle treated with lamotrigine were identified and
      classified in three groups according to the medication used after patent expiry:
      original brand only, generic brand only, or both generic and original brand. The
      defined daily dose (DDD) of lamotrigine was calculated for each patient and the
      data collected for each class. Thereafter a data search was carried out in the
      database from the department of Clinical Biochemistry in order to find
      corresponding patient levels of lamotrigine in plasma. RESULTS: The median plasma
      concentrations of lamotrigine before and after patent expiry for patients treated
      with the original brand only were 21.0 mmol/L before and 22.0 mmol/L after. For
      patients who changed their treatment from the original to the generic brand the
      concentrations were 15.5 mmol/L before and 20.5 mmol/L after. For patients who
      changed their treatment from the original to a mixture of original and generic
      brand the concentrations were 17.0 mmol/L before and 19.5 mmol/L after. The
      median of drug use of lamotrigine before/after patent expiry for patients
      mentioned in the same order was 167.5 DDD before and 141 DDD after (original
      after); 156 DDD before and 161 DDD after (generic only) and 147.5 DDD before and
      160.5 DDD after (generic/original after). CONCLUSION: Generic lamotrigine does
      not lead to changes in plasma concentrations or larger variation in plasma
      concentrations. Consequently, there is no evidence to support that the effect is
      different when comparing the original brand and generic brands of lamotrigine.
      Further documentation can only be obtained by registering the numbers of seizures
      and side effects in a study comparing generic lamotrigine and the original brand.

PMID- 17553383
TI  - [Follow-up on patients 4 years after a stay at the Centre for Lifestyle at
      Braedstrup Hospital].
AB  - INTRODUCTION: There is a need to know what methods can be used in the treatment
      of life-style-related health problems. The aim of the study was to explore
      patients assessment of the benefits of a stay at the Centre for Lifestyle at
      Braedstrup Hospital. MATERIALS AND METHODS: Patients referred to the centre had
      severe health problems related to unhealthy lifestyles. The treatment included
      2x4-day stays and an out-patient follow-up day at 3-month intervals. In 2004, a
      questionnaire was sent to all patients who had a stay during the period 1999
      2001, asking them to identify their benefits from the stay. The data were
      compared with similar data from the beginning of their stay. RESULTS: A total of
      410 patients had a referral due to cardiovascular (CVD) disease, diabetes or
      chronic obstructive pulmonary disease (COPD). 11 had died and 341 (85.5%)
      answered the questionnaire. Between 71-87% of the patients stated that their stay
      had made them improve their eating habits, increase their physical activity,
      change their lifestyle to the benefit of their health and had increased their
      motivation to change their lifestyle. About 60% reported better physical and
      mental health and increased quality of life. The proportion of patients with good
      or very good health had increased from 26-48%, and the proportion that more or
      less could do whatever they wanted to had increased from 39-47%. Their body mass
      index had decreased by an average of 1.6 kg/m2, corresponding to a weight loss of
      6 kg (5.5%). CONCLUSION: Patients with lifestyle-related health problems report
      and show a positive effect of a stay at the Centre for Lifestyle 4,5 years after
      referral.

PMID- 17553384
TI  - [Carbon monoxide deaths caused by town gas in Denmark 1995-99].
AB  - INTRODUCTION: Over the years town gas has caused many fatal carbon monoxide
      poisonings. The aim of this paper is to document the circumstances surrounding
      town gas deaths in Denmark between 1995-1999 and to trace the development of
      these deaths in recent decades. MATERIALS AND METHODS: A retrospective study of
      death certificates and report material concerning carbon monoxide deaths in
      Denmark between 1995-1999 caused by town gas. Of 449 non-fire related carbon
      monoxide poisonings, 22 (4.9%) were caused by town gas. RESULTS: The deaths
      consisted of fourteen suicides, six accidents, and two with undetermined manner
      of death. Ten (71%) of the suicide victims were men and four (29%) were women,
      with an average age of 48 years (24-82 years); all had turned on two or more gas
      rings. The accident victims were one man and five women, with an average age of
      84 years (77-92 years); all had only turned on one gas ring. CONCLUSION: The
      number of town gas deaths has been drastically reduced since 1969, which can be
      explained by the reduced number of town gas installations containing carbon
      monoxide as well as preventive measures. Most deaths can probably be avoided when
      the town gas supply is switched to carbon monoxide-free town gas in 2007, but it
      is important to be aware that incomplete combustion of carbon monoxide-free town
      gas can still lead to carbon monoxide poisonings.

PMID- 17553385
TI  - [Differences in the prescription of analgesics in the treatment of cancer pain in
      six Danish pain treatment units].
AB  - 30-40% of cancer patients suffer from pain at diagnosis while 70-80% of patients
      at progressed stages of the disease suffer from pain. Background pain is treated
      with long-acting opioids. Breakthrough pain can be treated with shorter acting
      non-opioid analgesics or opioids. The aim of this study was to describe the
      medical treatment of pain in cancer patients in connection with six Danish
      hospital units with special expertise in pain treatment. Differences in the
      prescription of analgesics were studied. The study was performed as a cross
      section study of prescribed analgesics. Data was collected by reviewing medical
      records. The study included 347 patients. A total of 278 patients out of 347 were
      treated with opioids for background pains. A significant difference was found (P
      < 0.001) in the frequency of prescribing morphine, oxycodone and fentanyl. For
      the treatment of background pain secondary analgesics were prescribed for 40% of
      the patients while 50% of the patients were treated with paracetamol and/or
      NSAID. According to the medical records 79% of the patients were prescribed
      analgesics for breakthrough pain. 73% of the 347 patients had strong opioids
      prescribed for breakthrough pain. For the treatment of background pain opioids
      were prescribed for the majority of the cancer patients. Morphine and oxycodone
      were prescribed most frequently. Secondary analgesics and paracetamol and/or
      NSAID were also prescribed for background pain. The strong opioids were
      prescribed for the treatment of breakthrough pain. Differences in the
      prescription of analgesics between the six hospital units were observed in this
      study.

PMID- 17553386
TI  - [Prevalence of coeliac disease (CD) in children with type 1 diabetes (T1D)].
AB  - This screening study was performed to determine the prevalence of coeliac disease
      (CD) in children with type 1 diabetes (T1D) and to estimate the clinical effects
      of a gluten-free diet. In the region of Southern Denmark all patients under 16
      years of age with T1D were identified and 269 (89%) were included. CD was
      diagnosed in 33 (12.3%). Patients with CD had a lower height SDS and weight SDS
      and were younger at diabetes onset. After 2 years on a gluten-free diet there
      were significant improvements in clinical and biochemical parameters. We
      recommend screening of CD in all children with T1D.

PMID- 17553387
TI  - [De novo development of dyspnoea in a young healthy woman with fatal outcome].
AB  - A 20-year old previously healthy woman who had been taking oral contraceptives
      for 2 years develops increasing dyspnoea, general ill-feeling and lower back pain
      over a matter of weeks. During this time she attends her general practitioner
      several times. She is primarily treated for what is interpreted as asthma and
      later for pneumonia due to the increase in CRP (C-reactive protein). Finally, she
      is admitted to hospital with severe dyspnoea, cyanosis, and un-measurable blood
      pressure. She is referred immediately to MR scan, but suffers heart arrest in
      bed. Twenty minutes' attempt to revival was in vain. Medicolegal obduction
      demonstrates severe double pulmonary embolism (saddle embolism). When a young
      previously healthy woman develops dyspnoea, the possibility of pulmonary embolism
      should be in mind because timely diagnosis and treatment is crucial for the
      prognosis. Oral contraceptives should be discontinued already at the suspicion of
      a pulmonary embolism as combined hormonal contraception has thrombogenic
      properties.

PMID- 17553388
TI  - [Necrotising granulomatous inflammation with middle ear the only localisation].
AB  - Aggressive sarcoidosis is seldom described with the middle ear as the only
      localisation. A case is described, and differential diagnoses, such as
      tuberculosis, histocytosis X, Wegener's granulomatosis, paraffinoma, sarcoidosis
      and necrotising sarcoid granulomatosis are discussed.

PMID- 17553389
TI  - [Glucagon-like peptide 1 in the treatment of patients with type 2 diabetes].

PMID- 17553390
TI  - [GLP-1-based treatment of type 2 diabetes mellitus].
AB  - GLP-1 is secreted from the small intestine in response to ingestion of nutrients.
      It has a powerful insulinotropic effect and stimulates beta-cell growth and is
      therefore being developed for treatment of type 2 diabetes. The GLP-1 analogue,
      exenatide, is on the market in the USA as an add-on therapy. Another strategy to
      increase circulating GLP-1 is to inhibit the enzyme DPP-IV which degrades
      endogenous GLP-1. GLP-1-based therapy results in HbA1c reductions of
      approximately 1 percent point, and the lack of serious side effects and the low
      risk of hypoglycaemic episodes are unique traits.

PMID- 17553391
TI  - [Arterial puncture].

PMID- 17553392
TI  - [Effect of incretin hormones GIP and GLP-1 for the pathogenesis of type 2
      diabetes mellitus].
AB  - Oral administration of glucose stimulates insulin secretion to a greater extent
      than does glucose administered as an isoglycaemic intravenous glucose infusion.
      This phenomenon is called the incretin effect and is caused by the two incretin
      hormones GIP and GLP-1. In patients with type 2 diabetes, the incretin effect is
      impaired. The mechanisms of the impaired incretin effect have been found to
      involve reduced secretion of GLP-1 and a severely impaired effect of GIP. It is
      currently unknown whether these defects are consequences of the diabetic state or
      primary pathogenetic factors.

PMID- 17553393
TI  - [First 10 years with the Danish Registry of Childhood Diabetes].
AB  - The nation-wide Danish Registry of Childhood Diabetes and associated biological
      bank were established in 1996. All children diagnosed with insulin-dependent
      diabetes mellitus (IDDM) under the age of 15 years are included. In the period
      1996-2004 the incidence of IDDM in childhood and adolescence (0-15 years) has
      increased by 3.5% per year and was 25.7/100.000 in 2004. The average measured
      glycosylated haemoglobin (HbA1c) value has decreased over the period and was 8.4%
      in 2005. A registry of type 1 diabetes with a high degree of completeness is
      feasible, provides useful information about the quality of patient care and is a
      valuable resource for research.

PMID- 17553394
TI  - [Primary visitation of elective referred geriatric patients--a randomised study
      of home visits compared to day hospital visits].
AB  - AIM: To compare the treatment, patient satisfaction, life quality and costs of
      elective referred patients seen by a geriatric team at home or in a geriatric day
      hospital. MATERIALS AND METHODS: Elective patients were randomised to primary
      contact by home visit (n=175) or to primary contact in the day hospital (n=176),
      median age 81 and 83 years, median Barthel - index 85 and 85, MMSE 25 and 25. 61%
      of elective referrals were randomised. RESULTS: There were no differences between
      the two groups' number of problems regarding referrals, treatment offered, number
      of blood tests, number of X-rays, number of outpatient contacts, number of
      admissions to hospital wards or number of diagnosis. The patient had to invest on
      average 99.5 min together with the geriatric team at the first visit at home and
      57.7 min on following visits. The patient had to invest more time if seen in the
      day hospital: 159.0 min. at the first visit and 120 min. at the following visits.
      Despite this difference in time-consumption, no differences were found in patient
      satisfaction or life quality. Of the overall time used by the geriatric team for
      home visits 20% was used for transportation at the first visit and 30% at the
      following visits. On average the hospital costs were 3.50 hours/activity at home
      visits as compared to 1.55 hours/activity in the day hospital. CONCLUSION:
      Geriatric home visits are expensive and time-consuming.

PMID- 17553395
TI  - [Geriatric home visits can prevent hospitalisation of subacute patients but is
      time-consuming. A randomised study].
AB  - AIM: To study if geriatric home visits could prevent hospital admittance of
      geriatric patients referred subacute by general practitioners. MATERIALS AND
      METHODS: Patients were randomised to first contact by geriatric home visit
      (n=59), or to subacute admittance to a geriatric ward (n=43), median age 79.0 and
      82.5 years, women 64% and 72%, Barthel-index 755 and 770 and MMSE 24,0 and 23,0.
      Only 30% of the total number of subacute referred patients were included.
      RESULTS: 53% (31/59) randomised to home visits were not admitted to hospital, 17%
      (10/59) were admitted at the first home visit and 12% (7/59) within the first 7
      days. Patients admitted within the first 7 days were more often single, 84%
      (n=16/19) as compared to 52% (16/31) of those not admitted. The time used on home
      visits was on average 122 min, including 23 min (19%) for transportation. Among
      the 43 patients randomised to subacute admittance 16% (7/43) were sent home
      within 24 hours, and of these 73% were seen in the outpatient clinic, 26% (11/42)
      were sent home on day 2-7 and of these 27% were seen in the outpatient clinic.
      The overall median time in contact with the geriatric department was 27.1 days
      (n=59) in the home visit group and 15.0 days (n=43) in the admitted group
      (p<0.05). There were no significant differences in patient satisfaction or self
      rated health. The average time used by the municipality for home service was
      reduced to 15 min/day in patients sent to hospital (p<0.01) and increased to 44
      min/day in patients not admitted (p<0.05). CONCLUSION: Hospital admittance was
      avoided by geriatric home visits. However, time consumption was high. The
      municipality costs increased for non-admitted patients. The overall time in
      contact with the geriatric department was shortest for admitted patients.

PMID- 17553396
TI  - [Compulsive treatment in a psychiatry--an economic evaluation of participation in
      the Breakthrough model].
AB  - BACKGROUND: By use of the Breakthrough Series Collaborative a national quality
      project was launched in Denmark in 2004. The purpose was to improve the quality
      of compulsive treatment. Due to participation in the project the psychiatric ward
      at Herning Hospital reduced the frequency and duration of compulsive treatment
      significantly compared to 2003. The objective of this study was to evaluate
      changes in costs per discharged patient and bed-day before and after the
      intervention. To illustrate quality improvements beyond the purpose of the
      national project the consumption of antipsychotics was included in the
      evaluation. MATERIALS AND METHODS: Specification of working hours per discharged
      patient and bed-day and an average hourly rate for a nurse provide the basis for
      the valuation. The cost of antipsychotics is based on an average daily use per
      discharged patient and bed-day. The monetary unit is Danish Kroner. RESULTS: The
      wage costs per discharged patient were 18,487 before and 19,010 after the
      intervention. Per bed-day the costs were 2,642 and 2,679, respectively. Medicine
      costs per discharged patient were 198 before and 148 after the intervention while
      the costs per bed-day were 28 and 21, respectively. CONCLUSION: This evaluation
      of costs shows that it is possible to develop and implement quality improvements
      without increasing costs. A decrease in medicine costs indicates that the effect
      reaches further than the quality in compulsive treatment.

PMID- 17553397
TI  - [The treatment of hyperemesis gravidarum with chlorobutanol-caffeine rectal
      suppositories in Denmark: practice and evidence].
AB  - INTRODUCTION: In Denmark chlorobutanol-caffeine rectal suppositories are
      prescribed by some obstetric departments for the treatment of hyperemesis
      gravidarum. MATERIALS AND METHODS: We have investigated the extent of this use by
      questionnaire, and we have performed a literature review on the evidence of
      efficacy and safety. RESULTS: The use of chlorobutanol-caffeine rectal
      suppositories was reported by 5 out of 28 obstetric departments in Denmark. The
      literature search revealed that there is very sparse information on
      chlorobutanol. No evidence was found of safety during pregnancy in humans or
      efficiency as antiemetic treatment in hyperemesis gravidarum. CONCLUSION: There
      is no evidence of the efficacy or safety of chlorobutanol-caffeine suppositories
      for the treatment of hyperemesis gravidarum.

PMID- 17553398
TI  - [Chancroid].
AB  - Chancroid is caused by the bacterium Haemophilus ducreyi. It is a sexually
      transmitted disease causing a soft chancre with a necrotic base and purulent
      exudate. The incidence of this illness is very low in Denmark and is probably
      underestimated. The bacterium is very fragile in transport, and culture is often
      negative. The chance of demonstrating the bacterium is greatly enhanced by the
      use of molecular techniques. In this case, we report on a specific PCR test for
      H. ducreyi that was used to establish the diagnosis in a 40-year-old male.

PMID- 17553399
TI  - [Pyomyositis in children--a diagnostic challenge!].
AB  - This report describes two children with fever and musculoskeletal pain diagnosed
      as pyomyositis, an acute bacterial infection in skeletal muscles that produces
      diffuse inflammation and suppuration. The diagnosis is reported with increasing
      frequency in non-tropical areas. The condition should be kept in mind in cases of
      musculoskeletal pain, fever and general malaise, and MRI should be performed to
      verify the diagnosis. S. aureus is the most commonly responsible organism. Cure
      is usually achieved through relevant antibiotic therapy, combined with drainage
      in case of suppuration. Early diagnosis and treatment are crucial to a good
      prognosis.

PMID- 17553400
TI  - [Open letter from the President of the Spanish Association of Surgeons].

PMID- 17553401
TI  - [Wireless capsule endoscopy: basic principles and clinical utility].
AB  - Wireless capsule endoscopy (PillCam) represents a major advance in the study of
      small bowel disease since this procedure allows images of hitherto unreachable
      areas to be obtained. Approved for use by the Food and Drug Administration in
      August 2000, capsule endoscopy is currently a first line procedure in the study
      of small bowel disease. This technique consists of a non-reusable swallowable
      capsule (length 26 x 11 mm) that acquires video images while moving through the
      gastrointestinal tract propelled by natural peristalsis. The main indications of
      capsule endoscopy are evaluation of obscure gastrointestinal bleeding, chronic
      anemia, and inflammatory bowel disease. Contraindications are swallowing
      disorders and known or suspected small bowel strictures of any etiology.
      Consequently, small bowel follow through is useful prior to capsule endoscopy
      when these lesions are suspected.

PMID- 17553402
TI  - [Multimodal rehabilitation in colorectal surgery. On resistance to change in
      surgery and the demands of society].
AB  - Perioperative management is one of the fields of surgery most hide bound by
      tradition and conventional attitudes are difficult to modify even in the face of
      strong scientific evidence. One of the advances that has most helped to improve
      the results of colorectal surgery is multimodal or fast-track rehabilitation,
      which aims to enhance recovery, reduce morbidity, and shorten the length of
      hospital stay. This modality is based on a multidisciplinary approach provided by
      surgeons, anesthesiologists and other staff and aims to decrease the response to
      physiopathological changes induced by surgical aggression. There is evidence to
      support the use of preoperative oral carbohydrate therapy and oral bowel
      preparation, the avoidance of intraoperative fluid excess, and the maintenance of
      normothermia on postoperative recovery. Other factors that can also reduce
      complications are epidural analgesia, avoidance of drainage and nasogastric
      decompression, early oral feeding, and minimally invasive surgery. There is
      strong evidence that the combined use of these and other measures enhances
      postsurgical recovery, although many of these measures are currently little used
      in daily practice.

PMID- 17553404
TI  - [Prevention of surgical infection using reabsorbable antibacterial suture (Vicryl
      Plus) versus reabsorbable conventional suture in hernioplasty. An experimental
      study in animals].
AB  - INTRODUCTION: Surgical site infections are frequent in daily surgical practice.
      One of the main challenges currently facing surgeons is the prevention and
      treatment of infections, especially those involving prosthetic material. A new
      suture (Vicryl Plus) has become available. In vitro studies and experimental
      models have demonstrated the ability of this suture to inhibit bacterial growth
      and consequently prevent postsurgical infection. OBJECTIVES: To compare
      infections provoked in prosthetic implants fixed with reabsorbable conventional
      sutures with those in meshes fixed with reabsorbable sutures with antiseptic
      impregnation. MATERIAL AND METHOD: Twenty white Wistar rats were used. In each
      rat, two hernioplasties were performed: one fixed with Vicryl Plus and the other
      with normal Vicryl. Subsequently, each polypropylene mesh was infected with S.
      aureus, and the rats remained in individual cages for a week. After 1 week, the
      rats were sacrificed and the meshes were extracted for macroscopic, microscopic
      and microbiologic study. RESULTS: Most of the meshes fixed with the new suture
      (Vicryl Plus) showed macroscopically fewer infections than those fixed with
      conventional suture, without abscesses and without dehiscence of the
      hernioplasty. In the microbiological quantitative bacterial study, the number of
      bacteria quantified per gram of sample was also lower in prostheses fixed with
      Vicryl Plus. Pathological analysis showed lesser colonization of the mesh and
      lower inflammatory response with Vicryl Plus than with normal Vicryl. In the
      statistical analysis, comparison of the medians of both groups and the
      interquartile ranges of microbial quantification revealed a lower infection rate
      in the Vicryl Plus group. CONCLUSIONS: The infection rate in the surgical site
      can be reduced by mesh fixation using the new antimicrobial suture (Vicryl Plus).
      We believe that this type of suture constitutes a new weapon in the fight against
      postoperative infection, especially in hernioplasty, emergency surgery, and dirty
      or potentially contaminated surgery.

PMID- 17553403
TI  - [Severe pelvic fractures, associated injuries and hemodynamic instability:
      incidence, management and outcome in our center].
AB  - INTRODUCTION: The aim of this study was to review the incidence, treatment and
      outcome of severe pelvic fractures, as well as associated injuries, in our
      center. PATIENTS AND METHOD: We performed a retrospective study of patients
      included in our trauma registry between June 1993 and January 2005. Pelvic
      fractures were classified according to the system proposed by Tile. Clinical and
      demographic data such as age, gender, mechanism of injury, transfer time,
      hemodynamic status, and trauma scores were compared and analyzed statistically.
      Shock was defined as a systolic blood pressure of < or = 90 mmHg during the
      primary assessment. Mortality and associated risk factors were analyzed, with
      emphasis on patients in shock on admission. RESULTS: Of 1274 patients with severe
      trauma admitted during the study period, 192 (15%) had pelvic fracture. Only 6.7%
      were isolated fractures and 6% were open fractures. Twenty percent of the
      patients were in shock on admission. The mean Injury Severity Score of the series
      was 28.5 +/- 14 and that of patients in shock was 38 +/- 16. The most frequently
      associated injuries were thoracic (70%), abdominal (55%), long bone fractures
      (52%), and head injuries (40%). Twenty-three percent of the patients had
      retroperitoneal hematoma. Arteriograms were performed in 16 patients, with four
      embolizations. Eight patients underwent external orthopedic fixation, and none
      posterior orthopedic fixation. Five patients underwent pelvic packing and two
      patients underwent ligation of hypogastric arteries. Overall mortality was 30%
      and mortality in patients in shock was 61%. Predictors of mortality were shock on
      admission, a Glasgow Coma Scale score of < or = 8, ISS > 25 and age > 55 years.
      CONCLUSIONS: Patients in shock with pelvic fractures have a poor prognosis in our
      center, frequently related to the severity of associated injuries, the relative
      rarity of these fractures, and the lack of a clearly defined management protocol.
      The main cause of death was massive hemorrhage.

PMID- 17553405
TI  - [Treatment of non-midline ventral hernia: experience in an abdominal wall unit
      and literature review].
AB  - INTRODUCTION: Lateral ventral hernia is an interesting surgical problem. However,
      few data are available on this entity. OBJECTIVE: To review current knowledge of
      lateral ventral hernia and present our experience of this entity in a
      multidisciplinary abdominal wall unit. PATIENTS AND METHOD: A. LITERATURE REVIEW:
      a search of Spanish (Cirugia Espanola) and international literature was performed
      through MEDLINE using the key words "lateral incisional/ventral hernia". B.
      Clinical study: a series of 53 patients who underwent endoscopic surgery for non
      midline ventral hernia were prospectively studied. Clinical parameters,
      postoperative complications and the recurrence rate were evaluated. The mean
      follow-up was 64 months (range, 12-120 months). RESULTS: A. LITERATURE REVIEW: we
      found a ratio between chapters on inguinal hernia and ventral hernia of 3.8:1 and
      a complete absence of chapters on lateral ventral hernia. Only two articles
      specifically dealt with ventral hernia. B. Clinical study: the most frequent
      location was lumbar (34%), followed by iliac and subcostal. A total of 37.7% of
      patients could be treated without admission and the remaining patients had a mean
      length of hospital stay of 2.7 days. Hematoma (17%) predominated in iliac ventral
      hernias and pain was transitory in two patients with lumbar ventral hernia. There
      were two early recurrences due to incorrect mesh fixation in subcostal and lumbar
      ventral hernias. CONCLUSIONS: Non-midline ventral hernia is a little known
      entity. Future treatment should be individualized in each patient and should be
      based on common classification of the type of defect to correctly evaluate the
      results. The laparoscopic route provides competitive results in selected
      patients.

PMID- 17553406
TI  - [Analysis of the results of a short-stay thoracic surgery program (2001-2005)].
AB  - INTRODUCTION: A short-stay thoracic surgery program was implemented and a
      prospective study was initiated to evaluate its results. OBJECTIVE: To analyze
      the results of the short-stay thoracic surgery program. PATIENTS AND METHOD: The
      results of 350 procedures (283 lobectomies and 67 pneumonectomies) performed
      between 2001 and 2005 were analyzed. The variables analyzed were: a) mean length
      of stay, b) mortality, c) complications, and d) readmission rate. RESULTS: The
      mean length of postoperative stay was 5.8 +/- 2.8 days for lobectomy and 5.36 +/-
      1.8 days for pneumonectomy. Mortality was 3.5% in lobectomy and 3% in
      pneumonectomy. Complications occurred in 17.3% of lobectomies and 23.8% of
      pneumonectomies. The readmission rate was 7%. CONCLUSIONS: The results obtained
      show that, as expected, the short-stay thoracic surgery program reduces the mean
      length of hospital stay. Moreover, this program is safe, since mortality and
      morbidity were lower than or similar to the mean and the readmissions rate was
      similar to the national average. These results have encouraged us to continue the
      program started in 1998.

PMID- 17553407
TI  - [Surgical resection of liver metastases from colorectal carcinoma. Experience in
      Sant Pau Hospital].
AB  - INTRODUCTION: Surgical resection is the only available treatment that improves
      survival in patients with liver metastases from colorectal cancer, particularly
      when carried out by a multidisciplinary team. MATERIAL AND METHOD: We
      retrospectively analyzed a consecutive series of 116 patients who underwent 138
      liver resections (65.4% minor and 35.5% major) for hepatic metastases from
      colorectal cancer between 1998 and 2004. In 34.5% of the patients, the lesions
      were synchronous. All patients were individually assessed by a multidisciplinary
      team. The mean number of metastases removed per patient was 2.43 (range: 1-10).
      The mean size of the largest tumor per patient was 40 mm (range: 12-90). In 67.3%
      of the patients, the primary tumor was at an advanced stage (III-IV). In 98% of
      the patients, the diagnosis was confirmed by helical computed tomography
      scans/magnetic resonance imaging and intraoperative ultrasonography. RESULTS:
      Postoperative morbidity was 31.2% and mortality was 2.2%. A mean of 2.7 units of
      blood was transfused per patient. Overall 5-year survival was 43.2% (median 50
      months). Survival rates varied according to whether the patients had < 4 or > or
      = 4 colorectal liver metastases (50 and 43 months respectively), tumor size (more
      or less than 5 cm) (60 and 50.6 months respectively) and whether the site was
      monolobar or bilobar (60 and 43.11 months respectively). In 16 patients,
      recurrence of liver metastases led to 22 rehepatectomies. Overall 5-year survival
      was 36.7% (median 60 months) after the first rehepatectomy but was 36 and 12
      months respectively after a second or third rehepatectomy. CONCLUSIONS: These
      results confirm that multidisciplinary decisions and interventions by specialist
      liver surgeons, as in our hospital, reduce postoperative morbidity and mortality
      and increase survival in patients requiring surgical removal of liver metastases
      from colorectal cancer.

PMID- 17553408
TI  - [Intraductal breast papillomas in patients with Costello syndrome].
AB  - Costello syndrome is a multisystemic congenital disorder with a very low
      prevalence. The pathogenesis remains unclear and predisposes to the development
      of tumors of ectodermal origin. Diagnosis is clinical, based on findings of
      mental and growth retardation and a characteristic phenotype. We report the case
      of a patient with Costello syndrome who was referred to our unit with a suspected
      diagnosis of intraductal papilloma based on the presence of various episodes of
      nipple discharge. Postoperative histopathological study confirmed the diagnosis
      of multiple intraductal papilloma. We review the literature on the topic and
      discuss the advisability of aggressive surgical therapy, given the predisposition
      of these patients to develop both benign and malignant tumors.

PMID- 17553409
TI  - [Hepatic artery aneurysm].
AB  - Hepatic artery aneurisms are infrequent and most are asymptomatic. Clinical
      presentation is variable but the most frequent form is rupture, complicated by
      hemoperitoneum and shock. We present the case of a patient who, 2 years after
      undergoing surgery for a dissecting aortic aneurysm, presented to the emergency
      room with obstructive jaundice, caused by a hepatic artery aneurism.

PMID- 17553410
TI  - [Localization of gastrointestinal bleeding from jejunal diverticuli by methylene
      blue dye].
AB  - Localization of digestive hemorrhage is essential for the management of this
      entity. However, management is difficult in the small bowel, where emergency
      situations are rare but may require surgery without precise location of the
      lesion. We present a case of hemorrhage caused by jejunal diverticulum diagnosed
      by angiography. A highly selective microcatheter was placed in the bleeding site
      to achieve staining of the lesion with intraoperative methylene blue.

PMID- 17553411
TI  - [Pancreatic mucinous cystadenocarcinoma].

PMID- 17553412
TI  - [Jejunal perforation due to gastrinoma].

PMID- 17553413
TI  - [Hyperparathyroidism and chronic lithium salt therapy].

PMID- 17553414
TI  - [Vascular complications associated with pancreatitis].

PMID- 17553415
TI  - [Adult colocolic intussusception secondary to inflammatory myofibroblastic
      tumor].

PMID- 17553416
TI  - A paradoxical role for inhibition in initiation.
AB  - Subliminal stimuli, of which subjects are unaware, affect movements made to
      subsequent visible cues. Sumner and colleagues in this issue of Neuron show that
      restricted supplementary motor and eye field lesions compromise voluntary control
      of action because they disrupt the normal unconscious and automatic inhibition of
      alternative movements partially activated by subliminal stimuli.

PMID- 17553417
TI  - Caspase-3 cleavage of GGA3 stabilizes BACE: implications for Alzheimer's disease.
AB  - BACE initiates the production of beta-amyloid (Abeta), the likely cause of
      Alzheimer's disease (AD). In this issue of Neuron, Tesco et al. show that during
      apoptosis caspase-3 cleaves the adaptor protein GGA3, which is required for BACE
      lysosomal degradation, consequently stabilizing BACE and elevating Abeta
      generation.

PMID- 17553418
TI  - Hierarchical control of sensory neuron development by neurotrophic factors.
AB  - We are still far from reaching a complete understanding of the molecular
      mechanisms that control neuronal diversification during nervous system
      development. In this issue of Neuron, Luo et al. bring that goal a step closer by
      revealing how a hierarchical interaction between two neurotrophic factor systems
      drives the differentiation, maturation, and extension of peripheral projections
      in a subclass of sensory neurons that mediate pain perception.

PMID- 17553419
TI  - Brain states: top-down influences in sensory processing.
AB  - All cortical and thalamic levels of sensory processing are subject to powerful
      top-down influences, the shaping of lower-level processes by more complex
      information. New findings on the diversity of top-down interactions show that
      cortical areas function as adaptive processors, being subject to attention,
      expectation, and perceptual task. Brain states are determined by the interactions
      between multiple cortical areas and the modulation of intrinsic circuits by
      feedback connections. In perceptual learning, both the encoding and recall of
      learned information involves a selection of the appropriate inputs that convey
      information about the stimulus being discriminated. Disruption of this
      interaction may lead to behavioral disorders, including schizophrenia.

PMID- 17553420
TI  - Human medial frontal cortex mediates unconscious inhibition of voluntary action.
AB  - Within the medial frontal cortex, the supplementary eye field (SEF),
      supplementary motor area (SMA), and pre-SMA have been implicated in the control
      of voluntary action, especially during motor sequences or tasks involving rapid
      choices between competing response plans. However, the precise roles of these
      areas remain controversial. Here, we study two extremely rare patients with
      microlesions of the SEF and SMA to demonstrate that these areas are critically
      involved in unconscious and involuntary motor control. We employed masked-prime
      stimuli that evoked automatic inhibition in healthy people and control patients
      with lateral premotor or pre-SMA damage. In contrast, our SEF/SMA patients showed
      a complete reversal of the normal inhibitory effect--ocular or manual-
      corresponding to the functional subregion lesioned. These findings imply that the
      SEF and SMA mediate automatic effector-specific suppression of motor plans. This
      automatic mechanism may contribute to the participation of these areas in the
      voluntary control of action.

PMID- 17553423
TI  - A hierarchical NGF signaling cascade controls Ret-dependent and Ret-independent
      events during development of nonpeptidergic DRG neurons.
AB  - NGF controls survival, differentiation, and target innervation of both
      peptidergic and nonpeptidergic DRG sensory neurons. The common receptor for GDNF
      family ligands, Ret, is highly expressed in nonpeptidergic neurons, but its
      function during development of these neurons is unclear. Here, we show that
      expression of Ret and its coreceptors GFRalpha1 and GFRalpha2 is dependent on
      NGF. GFR/Ret signaling, in turn, autoregulates expression of both GFRalpha1 and
      GFRalpha2 and promotes expression of TrpA1, MrgA1, MrgA3, and MrgB4, acquisition
      of normal neuronal size, axonal innervation of the epidermis, and postnatal
      extinction of the NGF receptor TrkA. Moreover, NGF controls expression of several
      other genes characteristic of nonpeptidergic neurons, such as TrpC3, TrpM8, MrgD,
      and the transcription factor Runx1, via a Ret-independent signaling pathway.
      These findings support a model in which NGF controls maturation of nonpeptidergic
      DRG neurons through a combination of GFR/Ret-dependent and -independent signaling
      pathways.

PMID- 17553421
TI  - GAB2 alleles modify Alzheimer's risk in APOE epsilon4 carriers.
AB  - The apolipoprotein E (APOE) epsilon4 allele is the best established genetic risk
      factor for late-onset Alzheimer's disease (LOAD). We conducted genome-wide
      surveys of 502,627 single-nucleotide polymorphisms (SNPs) to characterize and
      confirm other LOAD susceptibility genes. In epsilon4 carriers from
      neuropathologically verified discovery, neuropathologically verified replication,
      and clinically characterized replication cohorts of 1411 cases and controls, LOAD
      was associated with six SNPs from the GRB-associated binding protein 2 (GAB2)
      gene and a common haplotype encompassing the entire GAB2 gene. SNP rs2373115 (p =
      9 x 10(-11)) was associated with an odds ratio of 4.06 (confidence interval 2.81
      14.69), which interacts with APOE epsilon4 to further modify risk. GAB2 was
      overexpressed in pathologically vulnerable neurons; the Gab2 protein was detected
      in neurons, tangle-bearing neurons, and dystrophic neuritis; and interference
      with GAB2 gene expression increased tau phosphorylation. Our findings suggest
      that GAB2 modifies LOAD risk in APOE epsilon4 carriers and influences Alzheimer's
      neuropathology.

PMID- 17553422
TI  - Depletion of GGA3 stabilizes BACE and enhances beta-secretase activity.
AB  - Beta-site APP-cleaving enzyme (BACE) is required for production of the
      Alzheimer's disease (AD)-associated Abeta protein. BACE levels are elevated in AD
      brain, and increasing evidence reveals BACE as a stress-related protease that is
      upregulated following cerebral ischemia. However, the molecular mechanism
      responsible is unknown. We show that increases in BACE and beta-secretase
      activity are due to posttranslational stabilization following caspase activation.
      We also found that during cerebral ischemia, levels of GGA3, an adaptor protein
      involved in BACE trafficking, are reduced, while BACE levels are increased. RNAi
      silencing of GGA3 also elevated levels of BACE and Abeta. Finally, in AD brain
      samples, GGA3 protein levels were significantly decreased and inversely
      correlated with increased levels of BACE. In summary, we have elucidated a GGA3
      dependent mechanism regulating BACE levels and beta-secretase activity. This
      mechanism may explain increased cerebral levels of BACE and Abeta following
      cerebral ischemia and existing in AD.

PMID- 17553424
TI  - Regulation of dendritogenesis via a lipid-raft-associated Ca2+/calmodulin
      dependent protein kinase CLICK-III/CaMKIgamma.
AB  - Ca(2+) signaling plays a central role in activity-dependent regulation of
      dendritic arborization, but key molecular mechanisms downstream of calcium
      elevation remain poorly understood. Here we show that the C-terminal region of
      the Ca(2+)/calmodulin-dependent protein kinase CLICK-III (CL3)/CaMKIgamma, a
      membrane-anchored CaMK, was uniquely modified by two sequential lipidification
      steps: prenylation followed by a kinase-activity-regulated palmitoylation. These
      modifications were essential for CL3 membrane anchoring and targeting into
      detergent-resistant lipid microdomains (or rafts) in the dendrites. We found that
      CL3 critically contributed to BDNF-stimulated dendritic growth. Raft insertion of
      CL3 specifically promoted dendritogenesis of cortical neurons by acting upstream
      of RacGEF STEF and Rac, both present in lipid rafts. Thus, CL3 may represent a
      key element in the Ca(2+)-dependent and lipid-raft-delineated switch that turns
      on extrinsic activity-regulated dendrite formation in developing cortical
      neurons.

PMID- 17553425
TI  - Activity-regulated N-cadherin endocytosis.
AB  - Enduring forms of synaptic plasticity are thought to require ongoing regulation
      of adhesion molecules, such as N-cadherin, at synaptic junctions. Little is known
      about the activity-regulated trafficking of adhesion molecules. Here we
      demonstrate that surface N-cadherin undergoes a surprisingly high basal rate of
      internalization. Upon activation of NMDA receptors (NMDAR), the rate of N
      cadherin endocytosis is significantly reduced, resulting in an accumulation of N
      cadherin in the plasma membrane. Beta-catenin, an N-cadherin binding partner, is
      a primary regulator of N-cadherin endocytosis. Following NMDAR stimulation, beta
      catenin accumulates in spines and exhibits increased binding to N-cadherin.
      Overexpression of a mutant form of beta-catenin, Y654F, prevents the NMDAR
      dependent regulation of N-cadherin internalization, resulting in stabilization of
      surface N-cadherin molecules. Furthermore, the stabilization of surface N
      cadherin blocks NMDAR-dependent synaptic plasticity. These results indicate that
      NMDAR activity regulates N-cadherin endocytosis, providing a mechanistic link
      between structural plasticity and persistent changes in synaptic efficacy.

PMID- 17553426
TI  - Ca2+ requirements for cerebellar long-term synaptic depression: role for a
      postsynaptic leaky integrator.
AB  - Photolysis of a caged Ca(2+) compound was used to characterize the dependence of
      cerebellar long-term synaptic depression (LTD) on postsynaptic Ca(2+)
      concentration ([Ca(2+)](i)). Elevating [Ca(2+)](i) was sufficient to induce LTD
      without requiring any of the other signals produced by synaptic activity. A
      sigmoidal relationship between [Ca(2+)](i) and LTD indicated a highly cooperative
      triggering of LTD by Ca(2+). The duration of the rise in [Ca(2+)](i) influenced
      the apparent Ca(2+) affinity of LTD, and this time-dependent behavior could be
      described by a leaky integrator process with a time constant of 0.6 s. A
      computational model, based on a positive-feedback cycle that includes protein
      kinase C and MAP kinase, was capable of simulating these properties of Ca(2+)
      triggered LTD. Disrupting this cycle experimentally also produced the predicted
      changes in the Ca(2+) dependence of LTD. We conclude that LTD arises from a
      mechanism that integrates postsynaptic Ca(2+) signals and that this integration
      may be produced by the positive-feedback cycle.

PMID- 17553427
TI  - Endocannabinoid-mediated long-term plasticity requires cAMP/PKA signaling and
      RIM1alpha.
AB  - Endocannabinoids (eCBs) have emerged as key activity-dependent signals that, by
      activating presynaptic cannabinoid receptors (i.e., CB1) coupled to G(i/o)
      protein, can mediate short-term and long-term synaptic depression (LTD). While
      the presynaptic mechanisms underlying eCB-dependent short-term depression have
      been identified, the molecular events linking CB1 receptors to LTD are unknown.
      Here we show in the hippocampus that long-term, but not short-term, eCB-dependent
      depression of inhibitory transmission requires presynaptic cAMP/PKA signaling. We
      further identify the active zone protein RIM1alpha as a key mediator of both CB1
      receptor effects on the release machinery and eCB-dependent LTD in the
      hippocampus. Moreover, we show that eCB-dependent LTD in the amygdala and
      hippocampus shares major mechanistic features. These findings reveal the
      signaling pathway by which CB1 receptors mediate long-term effects of eCBs in two
      crucial brain structures. Furthermore, our results highlight a conserved
      mechanism of presynaptic plasticity in the brain.

PMID- 17553428
TI  - microRNA modulation of circadian-clock period and entrainment.
AB  - microRNAs (miRNAs) are a class of small, noncoding RNAs that regulate the
      stability or translation of mRNA transcripts. Although recent work has implicated
      miRNAs in development and in disease, the expression and function of miRNAs in
      the adult mammalian nervous system have not been extensively characterized. Here,
      we examine the role of two brain-specific miRNAs, miR-219 and miR-132, in
      modulating the circadian clock located in the suprachiasmatic nucleus. miR-219 is
      a target of the CLOCK and BMAL1 complex, exhibits robust circadian rhythms of
      expression, and the in vivo knockdown of miR-219 lengthens the circadian period.
      miR-132 is induced by photic entrainment cues via a MAPK/CREB-dependent
      mechanism, modulates clock-gene expression, and attenuates the entraining effects
      of light. Collectively, these data reveal miRNAs as clock- and light-regulated
      genes and provide a mechanistic examination of their roles as effectors of
      pacemaker activity and entrainment.

PMID- 17553429
TI  - Light entrainment of the mammalian circadian clock by a PRKCA-dependent
      posttranslational mechanism.
AB  - Light is the most potent stimulus for synchronizing endogenous circadian rhythms
      with external time. Photic clock resetting in mammals involves cAMP-responsive
      element binding protein (CREB)-mediated transcriptional activation of Period
      clock genes in the suprachiasmatic nuclei (SCN). Here we provide evidence for an
      additional photic input pathway to the mammalian circadian clock based on Protein
      Kinase C alpha (PRKCA). We found that Prkca-deficient mice show an impairment of
      light-mediated clock resetting. In the SCN of wild-type mice, light exposure
      evokes a transient interaction between PRKCA and PERIOD 2 (PER2) proteins that
      affects PER2 stability and nucleocytoplasmic distribution. These
      posttranslational events, together with CREB-mediated transcriptional regulation,
      are key factors in the molecular mechanism of photic clock resetting.

PMID- 17553441
TI  - Clinicians' practices related to management of filarial adenolymphangitis and
      lymphoedema in Orissa, India.
AB  - The Global Programme to Eliminate Lymphatic Filariasis (GPELF), which includes
      alleviation of disability and suffering of patients, is implemented primarily in
      India by primary health care system. The present study assesses the current
      practices related to lymphoedema care among clinicians of primary healthcare
      system in three filarial endemic districts of Orissa, India. The results are
      based on the data obtained through in-depth interviews with 50 clinicians from
      primary health centres (PHCs) and private clinics located in 22 PHCs sampled from
      three districts. All clinicians are aware of common as well as atypical
      manifestations of LF and offered treatment to them. The most commonly dealt
      complaints are lymphoedema of chronic LF and acute lymphangitis. All the
      clinicians reported that they prescribed diethylcarbamazine (DEC) for the
      treatment of patients with acute episodes, and only 50% of them prescribed
      antibiotics along with DEC. However, there is no uniform pattern either in the
      dosage of DEC or in the use of antibiotics. In this study, all the clinicians are
      aware that repeated acute episodes leads to lymphoedema. Majority of clinicians
      (94%) prescribed DEC to prevent this progression. For reduction of oedema, they
      offered a variety of treatments and more than half of the clinicians prescribed
      DEC. The study districts have been covered by the mass drug administration (MDA)
      of DEC under the GPELF. In order for the GPELF as a whole to prove successful and
      sustainable, those persons who are already suffering from LF need to be cared for
      and their suffering is to be relieved. Current practices of clinicians, both at
      government and private health institutions should be improved. With the revised
      knowledge that bacterial infections play a key role in the progression of
      disease, the attitude of clinicians towards the treatment of LF has to be
      changed.

PMID- 17553442
TI  - Transport of mercury through liquid membranes containing calixarene carriers.
AB  - Now membranes are widely used in many industries, e.g, dairy, food and beverage,
      electronics, starch and sweetener, water and wastewater treatment,
      pharmaceutical, biotechnology, environmental and so on. In addition to these,
      liquid membranes have received much attention for developing new, selective and
      stable systems to improve or perform separation processes involving specific
      chemical reactions such as ionic species, non-metallic species, bioactive
      materials, etc. In this aspect, liquid membranes have advantages for high
      selectivity towards specific ionic species and specific molecular recognition.
      Liquid membranes have a relatively high efficiency, and as such, are being looked
      into for industrial applications. We briefly discuss the transport kinetics of
      mercury using calixarene derivative carriers in liquid membranes and demonstrate
      various investigations regarding selective transport of mercury in particular
      using of various calixarene derivatives as a carrier. The review however does not
      cover all of the different approaches to liquid membrane transport, mercury
      transport or mercury removal.

PMID- 17553443
TI  - Wetting of low-energy surfaces.
AB  - Results of current theoretical methods for the calculation of contact angles on
      low-energy surfaces as functions of composition of solution and surface
      properties are reviewed.

PMID- 17553444
TI  - Surface forces and properties of foam films from rhamnolipid biosurfactants.
AB  - Foam films are considered as a convenient model to study the interaction
      behaviour and surface properties of microbial rhamnolipid type biosurfactants.
      The Scheludko-Exerowa microinterferometric methodology of film thickness
      measurements is employed for experimental studies of microscopic foam films
      formed from aqueous solutions of a single rhamnolipid Rh1 (with one rhamnosyl
      head group) and of mixtures of rhamnolipid surfactants Rh1 and Rh2 (with two
      rhamnosyl head groups) at ratios Rh2/Rh1=1.2 and Rh2/Rh1=0.69. The measurements
      of the equilibrium thickness (h) of the obtained films as a function of
      surfactant concentration (Cs) and electrolyte (NaCl) concentration (C el)
      determine the conditions for obtaining common, common black and Newton black
      films. The saturation values of the diffuse electric layer potential phi 0
      approximately 60 mV for the Rh1.2 and phi 0 approximately 94 mV for the Rh0.69
      common films conform the ionic character of the rhamnolipids. The h(C el) curves
      of the rhamnolipid foam films and the directly measured disjoining pressure
      (Pi(h)) isotherms indicate the ranges of action of the DLVO and non-DLVO surface
      forces. The obtained foam film parameters allow their practical use in ecology
      and in various technological processes where rhamnolipid surfactants are used.
      Experiments with model lung surfactant (Infasurf) foam films with rhamnolipid
      added outline a perspective for the potential application of the foam film for
      investigating the effect of rhamnolipids on human alveoli.

PMID- 17553445
TI  - Redundant publication of clinical trials on herpetic keratitis.
AB  - PURPOSE: To examine reported clinical trials on herpes simplex virus epithelial
      keratitis as a case study for the configuration and possible motives of
      overlapping publications in the ophthalmic literature. DESIGN: Cross-sectional
      bibliometric survey. METHODS: One hundred and forty-four reports of 98 randomized
      clinical trials that formed the framework for a systematic review on dendritic
      and geographic keratitis were assembled by electronic and manual searching of
      biomedical journals and transactions, excluding meeting abstracts. Overlapping
      reports were identified by comparing methods and results. Main articles giving
      the most detailed results among overlapping reports were contrasted with trial
      reports without duplication. Annual citation rates since publication were
      estimated from the number of times each report was cited by subsequent scientific
      articles indexed in an online citation database. RESULTS: Sixty-one articles were
      published once, while 83 articles overlapped in 23 clusters, of which 14 (50%)
      lacked bibliographic cross-reference. Of 55 secondary reports, 34 (62%) had a
      smaller sample size than their corresponding main report. Secondary articles were
      less likely to appear in an ophthalmological publication than main reports (P <
      .001) and were later cited less often (P = .01). Compared to trial reports
      published once, main articles with an overlapping report had a significantly
      higher citation rate (P = .04). CONCLUSION: Overlapping publications of
      therapeutic trials on herpetic keratitis often had undisclosed or fragmentary
      interconnections. Subsequent authors cited articles having an overlapping report
      more often than trials published once.

PMID- 17553446
TI  - Outcomes of epithelial debridement for anterior basement membrane dystrophy.
AB  - PURPOSE: To evaluate the outcomes of simple mechanical debridement for the
      management of anterior basement membrane dystrophy (ABMD) in a cohort of patients
      treated primarily for visual symptoms. DESIGN: Retrospective, observational case
      series. METHODS: setting: Single center. study population: Seventy-four eyes of
      55 patients treated with mechanical epithelial debridement over a 15-year period.
      observation procedures: We recorded symptoms, pre- and postoperative best
      corrected visual acuity (BCVA), surgical technique, complications, and evidence
      of disease recurrence. main outcome measures: Mean best-corrected logMAR acuity
      and refractive errors, compared by using paired t tests or Wilcoxon signed-rank
      tests. Interval to recurrence of ABMD was determined by using Kaplan-Meier
      estimates. RESULTS: Mean patient age was 74 years, and 80% were female. Visual
      difficulty was reported by the patient before the procedure in 61 eyes (82%), and
      erosion symptoms alone were noted before the procedure in the remaining 13 eyes.
      Mean BCVA improved from 20/44 before surgery to 20/30 (P = .0001) at the early
      follow-up visit and 20/33 (P = .0001) at the last follow-up (mean = 33 months).
      The mean refractive spherical equivalent changed -0.6 diopters (range, -4.75 to
      +2.0 diopters). No infections or persistent epithelial defects occurred. The most
      common postoperative complication was subepithelial haze, occurring in 19 eyes
      (26%). The five-year cumulative probability of recurrence of ABMD was 44.7%.
      CONCLUSIONS: Our results with this simple technique are comparable to outcomes
      reported with other procedures used to treat ABMD. We recommend manual
      debridement as an effective option for ABMD affecting visual acuity.

PMID- 17553447
TI  - Influence on posterior capsule opacification and visual function of intraocular
      lens optic material.
AB  - PURPOSE: To examine the influence of optic material on posterior capsule
      opacification (PCO) by comparing PCO and visual functions between eyes with an
      acrylic intraocular lens (IOLs) and those with a silicone IOL of the same optic
      design and with the same haptics. DESIGN: Randomized clinical trial. METHODS: One
      hundred patients scheduled for phacoemulsification surgery underwent implantation
      of an acrylic IOL (AMO Sensar; AR40e) in one eye and implantation of a silicone
      IOL (ClariFlex) of the same optic design and loops in the fellow eye. Eighty-nine
      patients (89%) remained for analysis. The PCO value was measured using the
      Scheimpflug videophotography system at one, three, six, 12, 18, 24, 30, and 36
      months postoperatively. The incidence of eyes that required a neodymium:yttrium
      aluminum-garnet (Nd:YAG) laser capsulotomy was examined; visual acuity and
      contrast sensitivity with and without a glare source were also evaluated.
      RESULTS: The mean PCO value did not increase significantly during follow-up in
      either the acrylic or silicone IOL group. When comparing the groups, no
      statistically significant difference was found in the PCO or in the incidence of
      Nd:YAG capsulotomy, although both tended to be slightly better in the silicone
      group than in the acrylic group. There was also no significant difference between
      the groups in visual acuity or in photopic and mesopic contrast sensitivity with
      or without glare. CONCLUSIONS: When acrylic and silicone IOLs are of the same
      optic design and with the same haptics, the optic material does not influence the
      development of PCO enough to impair visual function.

PMID- 17553448
TI  - The use of hepatitis C virus NS3/4A and secreted alkaline phosphatase to
      quantitate cell-cell membrane fusion mediated by severe acute respiratory
      syndrome coronavirus S protein and the receptor angiotensin-converting enzyme 2.
AB  - The membrane fusion process mediated by severe acute respiratory syndrome
      coronavirus (SARS-CoV) S protein and its cellular receptor angiotensin-converting
      enzyme 2 (ACE2) had been reconstituted using two Chinese hamster ovary (CHO) cell
      lines that constitutively express these recombinant proteins separately. This
      system was applied to develop a quantitative measurement of cell-cell fusion
      using hepatitis C virus (HCV) NS3/4A protease and a secretion-blocked EGFP-4A/4B
      SEAP (EGFP: enhanced green fluorescent protein; 4A/4B: a decapeptide substrate of
      NS3/4A protease; SEAP: secreted alkaline phosphatase) fusion gene. Both genes
      were transiently expressed in either of the CHO cell lines, followed by fusion
      treatment. Significant SEAP activity could be detected in the culture medium only
      after cell-cell fusion occurred. Cell-cell fusion provides an environment in
      which the protease encounters its substrate 4A/4B, thereby releasing SEAP from
      the fusion protein. In this study, we developed a simple, sensitive, and
      quantitative assay to study the membrane fusion process by measuring the
      extracellular activity of SEAP.

PMID- 17553449
TI  - Label-free detection of protein interactions using deep UV fluorescence lifetime
      microscopy.
AB  - We present a label-free detection of protein interaction between beta
      galactosidase from Escherichia coli (Ecbeta-Gal) and monoclonal anti-Ecbeta-Gal
      using deep UV laser-based fluorescence lifetime microscopy. The native
      fluorescence from intrinsic tryptophan emission was observed after one-photon
      excitation at 266 nm. Applying the time-correlated single-photon counting (TCSPC)
      method, we investigated the mean fluorescence lifetime and lifetime distributions
      from tryptophan residues in Ecbeta-Gal protein, monoclonal anti-Ecbeta-Gal, and
      corresponding complex. The results demonstrate that deep UV laser-based
      fluorescence lifetime microscopy is useful for sensitive identification of
      biological macromolecules interaction using intrinsic fluorescence.

PMID- 17553450
TI  - Separation and determination of in vitro oxidized phospholipids by capillary zone
      electrophoresis.
AB  - A simple capillary zone electrophoresis (CZE) method was used to determine in
      vitro oxidized phosphatidyl choline (ox-PC). To optimize the capillary
      electrophoresis (CE) conditions, organic buffer additives, buffer ionic strength,
      buffer pH, and applied voltage were examined. The optimal CE separation buffer
      chosen was an aqueous-organic solvent system containing 10% sodium phosphate
      buffer (5 mM, pH 7.40), 80% methanol, and 10% acetonitrile. One major peak with a
      small shoulder was found for phosphatidyl choline (PC), whereas one major peak
      and a complex region containing several lower-mobility peaks were found for ox
      PC. The lower-mobility species of ox-PC has high levels of conjugated dienes
      characterized by strong absorbance at 234 nm. The electropherograms of PC and ox
      PC were significantly different and highly reproducible. The intensities of lower
      mobility species decreased significantly when the antioxidant vitamin C
      concentration was increased from 6 to 600 microM. This study provides a simple
      CZE method to differentiate in vitro oxidized from nonoxidized PC molecular
      species.

PMID- 17553451
TI  - Steric analysis of 8-hydroxy- and 10-hydroxyoctadecadienoic acids and
      dihydroxyoctadecadienoic acids formed from 8R-hydroperoxyoctadecadienoic acid by
      hydroperoxide isomerases.
AB  - 8-Hydroxyoctadeca-9Z,12Z-dienoic acid (8-HODE) and 10-hydroxyoctadeca-8E,12Z
      octadecadienoic acid (10-HODE) are produced by fungi, e.g., 8R-HODE by
      Gaeumannomyces graminis (take-all of wheat) and Aspergillus nidulans, 10S-HODE by
      Lentinula edodes, and 10R-HODE by Epichloe typhina. Racemic [8-(2)H]8-HODE and
      [10-(2)H]10-HODE were prepared by oxidation of 8- and 10-HODE to keto fatty acids
      by Dess-Martin periodinane followed by reduction to hydroxy fatty acids with
      NaB(2)H(4). The hydroxy fatty acids were analyzed by chiral phase high
      performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) with 8R
      HODE and 10S-HODE as standards. 8R-HODE eluted after 8S-HODE on silica with
      cellulose tribenzoate (Chiralcel OB-H), and 10S-HODE eluted before 10R-HODE on
      silica with an aromatic chiral selector (Reprosil Chiral-NR). 5S,8R
      Dihydroxyoctadeca-9Z,12Z-dienoic acid (5S,8R-DiHODE) is formed from 18:2n-6 by A.
      nidulans and 8R,11S-dihydroxyoctadeca-9Z,12Z-dienoic acid (8R,11S-DiHODE) by
      Agaricus bisporus. 8R-Hydroperoxylinoleic acid (8R-HPODE) can be transformed to
      5S,8R-DiHODE and 8R,11-DiHODE by Aspergillus spp., and 8R,13-dihydroxy-9Z,11E
      dienoic acid (8R,13-DiHODE) can also be detected. We prepared racemic [5,8
      (2)H(2)]5,8- and [8,11-(2)H(2)]8,11-DiHODE by oxidation and reduction as above
      and 8R,13S- and 8R,13R-DiHODE by oxidation of 8R-HODE by S and R lipoxygenases.
      The diastereoisomers were separated and identified by normal phase HPLC-MS/MS
      analysis. We used the methods for steric analysis of fungal oxylipins.
      Aspergillus spp. produced 8R-HODE (>95% R), 10R-HODE (>70% R), and 5S,8R- and
      8R,11S-DiHODE with high stereoselectivity (>95%), whereas 8R,13-DiHODE was likely
      formed by nonenzymatic hydrolysis of 8R,11S-DiHODE.

PMID- 17553452
TI  - Real-time monitoring of uracil removal by uracil-DNA glycosylase using
      fluorescent resonance energy transfer probes.
AB  - As a highly conserved damage repair protein, uracil-DNA glycosylase (UDG) mainly
      catalyzes the excision of uracil from DNA to sustain the genome integrity. Here a
      novel method for monitoring the uracil removal in real time is introduced. Double
      stranded DNA probes modified with uracil residues that can occur in fluorescent
      resonance energy transfer (FRET) were used as substrates and detecting probes in
      a homogeneous solution. This method not only overcame the drawbacks of
      traditional radioactive assays, such as discontinuity and being time-consuming
      and complicated, but also was used to accurately determine the kinetic constant
      of UDG. The limit of detection of UDG was 0.033 U/ml. The KM and Kcat were 0.11
      microM and 4 s(-1), respectively. In addition, the method was applied to
      investigate the influence of chemical drugs on UDG activity. The results showed
      that 10 mM fluorouracil (5-FU) and gentamicin are inhibitors to UDG. The in vitro
      detection of UDG in A549 cells showed that the activity of UDG was four times
      greater after the cells were treated with cisplatin. These results showed that
      this method can monitor uracil removal in real time and conveniently assay UDG
      activity with ultrasensitivity and excellent specificity in the homogeneous
      solution. This method is also amenable to high-throughput drug screening in
      vitro.

PMID- 17553453
TI  - Single-pair fluorescence resonance energy transfer of nucleosomes in free
      diffusion: optimizing stability and resolution of subpopulations.
AB  - We applied fluorescence detection methods on the single-molecule level to study
      structural variations and dynamic processes occurring within nucleosomes. Four
      fluorescent nucleosome constructs were made by attaching donor and acceptor
      fluorophores to different positions of two nucleosome positioning sequences and
      reconstituting nucleosomes by salt dialysis. The photochemical and biochemical
      stability of nucleosomes under single-molecule conditions was optimized by adding
      inert protein and free radical capturing additives, allowing us to define the
      best experimental conditions for single-molecule spectroscopy on highly diluted
      solutions of nucleosome complexes. We could demonstrate for the first time the
      resolution of conformational subpopulations of nucleosomes by single-pair
      fluorescence resonance energy transfer in a freely diffusing system and could
      show the effect of thermally induced nucleosome repositioning.

PMID- 17553454
TI  - New continuous and specific fluorometric assays for Pseudomonas aeruginosa
      elastase and LasA protease.
AB  - A highly sensitive assay based on new internally quenched fluorogenic peptide
      substrates has been developed for monitoring protease activities. These novel
      substrates comprise an Edans (5-(2-aminoethylamino)-1-naphthalenesulfonic acid)
      group at the C terminus and a Dabsyl (4-(dimethylamino)azobenzene-4'-sulfonyl
      chloride) fluorophore at the N terminus of the peptide chains. The Edans
      fluorescence increases upon peptide hydrolysis by Pseudomonas aeruginosa
      proteases, and this increase is directly proportional to the amount of substrate
      cleaved, i.e., protease activity. The substrates Dabsyl-Ala-Ala-Phe-Ala-Edans and
      Dabsyl-Leu-Gly-Gly-Gly-Ala-Edans were used for testing the peptidasic activities
      of P. aeruginosa elastase and LasA protease, respectively. Elastase and LasA
      kinetic parameters were calculated and a sensitive assay was designed for the
      detection of P. aeruginosa proteases in bacterial supernatants. The sensitivity
      and the small sample requirements make the assay suitable for high-throughput
      screening of biological samples. Furthermore, this P. aeruginosa protease assay
      improves upon existing assays because it is simple, it requires only one step,
      and even more significantly it is enzyme specific.

PMID- 17553455
TI  - Near infrared multiphoton-induced generation and detection of hydroxyl radicals
      in a biochemical system.
AB  - Solutions of tryptophan and N-hydroxypyridine-2-thione (mercaptopyridine-N-oxide,
      MPNO) were irradiated at 335nm. Formation of 5-hydroxytryptophan was inferred
      from increased fluorescence at 334nm on excitation at 315nm, conditions chosen
      for selective detection of 5-hydroxytryptophan. Such experiments are complicated
      by overlapping absorption spectra in the region of 300-350nm. Similar solutions
      were exposed to multiphoton excitation at 750nm using 180fs pulses from a
      titanium:sapphire laser. In solutions containing both tryptophan and MPNO strong
      emission at 500nm was observed that was absent in solutions containing either
      MPNO or tryptophan only. This emission is ascribed to the characteristic
      fluorescence ('hyperluminescence') from 5-hydroxyindoles resulting from
      multiphoton photochemistry. The conclusion that MPNO generates hydroxyl radicals
      by 2-photon activation at 750nm is confirmed by the scavenging effects of ethanol
      and kinetic analysis of the results. This method has potential applications in
      intracellular induction of oxidative stress using multiphoton near-infrared
      illumination, a technology that is gaining momentum as a research tool.

PMID- 17553456
TI  - Amyloid beta ion channel: 3D structure and relevance to amyloid channel paradigm.
AB  - Alzheimer's disease (AD) is a protein misfolding disease. Early hypothesis of AD
      pathology posits that 39-43 AA long misfolded amyloid beta (Abeta) peptide forms
      a fibrillar structure and induces pathophysiological response by destabilizing
      cellular ionic homeostasis. Loss of cell ionic homeostasis is believed to be
      either indirectly due to amyloid beta-induced oxidative stress or directly by its
      interaction with the cell membrane and/or activating pathways for ion exchange.
      Significantly though, no Abeta specific cell membrane receptors are known and
      oxidative stress mediated pathology is only partial and indirect. Most
      importantly, recent studies strongly indicate that amyloid fibrils may not by
      themselves cause AD pathology. Subsequently, a competing hypothesis has been
      proposed wherein amyloid derived diffusible ligands (ADDLs) that are large Abeta
      oligomers (approximately >60 kDa), mediate AD pathology. No structural details,
      however, of these large globular units exist nor is there any known suitable
      mechanism by which they would induce AD pathology. Experimental data indicate
      that they alter cell viability by non-specifically changing the plasma membrane
      stability and increasing the overall ionic leakiness. The relevance of this non
      specific mechanism for AD-specific pathology seems limited. Here, we provide a
      viable new paradigm: AD pathology mediated by amyloid ion channels made of small
      Abeta oligomers (trimers to octamers). This review is focused to 3D structural
      analysis of the Abeta channel. The presence of amyloid channels is consistent
      with electrophysiological and cell biology studies summarized in companion
      reviews in this special issue. They show ion channel-like activity and channel
      mediated cell toxicity. Amyloid ion channels with defined gating and
      pharmacological agents would provide a tangible target for designing therapeutics
      for AD pathology.

PMID- 17553457
TI  - Diverse regulatory activity of human heat shock proteins 60 and 70 on endotoxin
      induced inflammation.
AB  - Tissue injury is often associated with bacterial infection. Intracellular heat
      shock proteins (HSPs) are released from damaged tissue, come in contact with
      cells of the immune system, and might affect the immune response against
      bacteria. In the present study, we investigated the capacity of highly purified
      human HSP60 and HSP70 to modulate the response of human peripheral blood-derived
      mononuclear cells (PBMC) to lipopolysaccharide (LPS). HSP70 but not HSP60
      decreased the LPS-induced secretion of TNF-alpha when added simultaneously with
      LPS. In contrast, HSP60 and HSP70 primed PBMC for enhanced secretion of TNF-alpha
      when added 24h prior to the stimulation with LPS. Neither HSP60 nor HSP70 alone
      induced the release of TNF-alpha. The capacity of LPS to bind to monocytes was
      not affected by HSPs, but HSP70 increased the expression of Toll-like receptor 4.
      Thus, HSP60 and HSP70 released upon tissue damage might play a role in the
      regulation of bacteria-induced inflammation.

PMID- 17553458
TI  - Haploinsufficiency of poly(ADP-ribose) polymerase-1-mediated poly(ADP
      ribosyl)ation for centrosome duplication.
AB  - The centrosome plays a vital role in maintaining chromosomal stability. Known as
      the microtubule organizing center, the centrosome is involved in the formation of
      spindle poles during mitosis, which ensures the distribution of the correct
      number of chromosomes to daughter cells. Aberrant centrosome duplication could
      cause centrosome amplification and chromosomal instability. We have previously
      shown that poly(ADP-ribose) polymerase-1 (PARP-1) is important for centrosome
      function and chromosomal stability. In this study, we used PARP-1(+/+), PARP-1(+/
      ) and PARP-1(-/-) primary mouse embryonic fibroblasts and found that the level of
      PARP-1 gene dosage correlates with PARP activity and the in vivo level of
      poly(ADP-ribosyl)ation, which could explain the mechanism by which PARP-1
      haploinsufficiency affects centrosome duplication and chromosomal stability. Our
      results emphasize that correct regulation of poly(ADP-ribosyl)ation levels in
      vivo is important for maintenance of proper centrosome duplication and
      chromosomal stability.

PMID- 17553459
TI  - Butyrate induces sLex synthesis by stimulation of selective glycosyltransferase
      genes.
AB  - Sialyl Lewis(x) (sLe(x)) is an important tumor-associated carbohydrate antigen
      present on the cell surface glycoconjugates involved in leukocyte migration and
      cancer metastasis. We report the formation of sLe(x) epitope in butyrate-treated
      human pancreatic adenocarcinoma cells expressing MUC1 and core 2 N
      acetylglucosaminyltransferase (C2GnT). Butyrate treatment stimulates not only the
      transgene but also a group of endogenous glycosyltransferase genes involved in
      the synthesis of sLe(x). Current finding raises a concern about the proposed use
      of butyrate as a cancer therapeutic agent.

PMID- 17553460
TI  - Support for a potential role of E. coli oligopeptidase A in protein degradation.
AB  - Protein degradation is an essential quality control and regulatory function in
      organisms ranging from bacteria to eukaryotes. In bacteria, this process is
      initiated by ATP-dependent proteases which digest proteins to short peptides that
      are subsequently hydrolyzed to smaller fragments and free amino acids. While the
      entire genome of Escherichia coli has been sequenced, identification of
      endopeptidases that perform this downstream hydrolysis remains incomplete.
      However, in eukaryotes, thimet oligopeptidases (TOP) has been shown to hydrolyze
      peptides generated by the degradation of proteins by the 26S proteasome. These
      findings motivated us to investigate whether E. coli oligopeptidase A (OpdA), a
      homolog of TOP might play a similar general role in bacterial protein
      degradation. Herein, we provide initial support for this hypothesis by
      demonstrating that OpdA efficiently cleaves the peptides generated by the
      activity of the three primary ATP-dependent proteases from E. coli-Lon, HslUV,
      and ClpAP.

PMID- 17553461
TI  - Transbilayer movement of ceramide in the plasma membrane of live cells.
AB  - Ceramide (Cer) is the precursor for sphingolipids and functions as a second
      messenger in a variety of cellular processes including apoptosis. However, no
      direct target of Cer leading to apoptosis has been identified. Understanding the
      movement and trafficking of Cer is important for fully understanding Cer
      signaling. In this study, we identified, for the first time, the transbilayer
      movement of Cer in the plasma membrane (PM) of living cells. We developed a new
      method to monitor transbilayer Cer movement using ceramide kinase activity. To
      produce Cer on the extracellular leaflet of the PM, bacterial sphingomyelinase
      (SMase) was added to rat basophilic leukemia cells. Interestingly, the dramatic
      elevation of ceramide 1-phosphate (C1P), the product of CerK, was observed
      following the increase of Cer induced by SMase treatment. Since we determined
      that both the protein and catalytic activity of CerK exists in the intracellular
      compartment, the all conversion of Cer to C1P by CerK should be occur
      intracellularly. This result indicates the rapid transbilayer movement of Cer
      from the outer leaflet to the inner leaflet of the PM of living cells.
      Furthermore, protease digestion of membrane proteins, inhibition of ABC
      transporters (by glibencramide) and of cation channels (by carbonyl cyanide m
      chlorophenylhydrozone), and modification of cholesterol content did not affect
      the transbilayer movement of Cer. Thus, this movement might occur spontaneously.
      Our findings indicate not only Cer movement in the PM, but also identify an
      intrinsic property of Cer enabling Cer signaling.

PMID- 17553462
TI  - E-LDL upregulates TOSO expression and enhances the survival of human macrophages.
AB  - Uptake of modified lipoproteins by macrophages causes foam cell formation and
      promotes atherosclerosis. Atherogenic lipoproteins are cytotoxic and induce cell
      death under certain conditions but may also enhance macrophage survival.
      Macrophages treated with enzymatically modified LDL (E-LDL) were subjected to
      GeneChip analysis and the antiapoptotic gene TOSO was found induced. TOSO mRNA is
      upregulated and apoptosis is reduced in E-LDL but not in oxidized LDL (Ox-LDL)
      loaded macrophages. FLIP(L) abundance was suggested to mediate the antiapoptotic
      properties of TOSO; however, FLIP(L) was not changed. Ox-LDL is internalized
      predominantly by scavenger receptors such as CD36 while E-LDL particles are
      preferentially internalized by Fc- and complement-receptor dependent phagocytosis
      and internalization of phagobeads by macrophages upregulates TOSO. In COS-7 cells
      however, phagocytotic activity was not affected by TOSO. These data indicate that
      E-LDL-generated foam cells are protected from cell death most likely through the
      expression of TOSO by a FLIP(L) independent mechanism.

PMID- 17553463
TI  - Post-translational modifications of collagen upon BMP-induced osteoblast
      differentiation.
AB  - The pattern of collagen cross-linking is tissue specific primarily determined by
      the extent of hydroxylation and oxidation of specific lysine residues in the
      molecule. In this study, murine pre-myoblast cell line, C2C12 cells, were
      transdifferentiated into osteoblastic cells by bone morphogenetic protein (BMP)-2
      treatment, and the gene expression of lysyl hydroxylases (LH1, 2a/b, and 3) and
      lysyl oxidase (LOX)/lysyl oxidase-like proteins (LOXL1-4), and the extent of
      hydroxylysine were analyzed. After 24h of treatment, the expression of most
      isoforms were upregulated up to 96h whereas LH2a and LOXL2 decreased with time.
      In the treated cells, both hydroxyproline and hydroxylysine were detected at day
      7 and increased at day 14. The ratio of hydroxylysine to hydroxyproline was
      significantly increased at day 14. The results indicate that LHs and LOX/LOXLs
      are differentially responsive to BMP-induced osteoblast differentiation that may
      eventually lead to the specific collagen cross-linking pattern seen in bone.

PMID- 17553464
TI  - Positional pathway screen of wnt signaling genes in schizophrenia: association
      with DKK4.
AB  - BACKGROUND: Wnt signaling has been implicated in schizophrenia from studies of
      gene expression in patients, from an understanding of the function of reported
      susceptibility genes and from experimental studies of psychoactive drugs. This
      diverse evidence suggests that wnt signaling genes, defined as pathway
      participants, modifiers or targets, are good candidates as susceptibility
      factors. METHODS: We performed a combined positional and candidate association
      screen by identifying known wnt signaling genes in regions linked to
      schizophrenia. In a staged study we examined over 50 single nucleotide
      polymorphisms (SNPs) in 28 wnt signaling genes, first in trios of Chinese origin
      and then in a case-control series from Hong Kong. RESULTS: In both sets, Dickkopf
      4 (DKK4) was associated with schizophrenia - with an odds ratio of 3.9 (p < .01,
      CI = 1.3-11.1) in the combined sample. CONCLUSIONS: As DKK family members have
      previously been found to show altered expression in schizophrenia brain and to
      bind to neuregulin, this finding suggests that DKK4 may play a role in
      schizophrenia pathogenesis.

PMID- 17553465
TI  - Associations between anxiety, depression, and the metabolic syndrome.
AB  - BACKGROUND: There is limited evidence as to whether the metabolic syndrome (MetS)
      is associated with depression or anxiety and, if so, whether this association is
      gender-specific. This study investigated in each gender whether the MetS is
      associated with anxiety or depression and whether these relationships are
      independent of age, obesity, smoking status, socioeconomic factors, and
      lifestyle. METHODS: Metabolic syndrome (American Heart Association/National
      Heart, Lung, and Blood Institute criteria), depression, and anxiety (Hospital
      Anxiety and Depression Scale) were assessed in 1598 subjects at risk of
      cardiovascular disease. RESULTS: In both men and women, the MetS was associated
      with an increased prevalence of depression but not anxiety. The number of
      components of the MetS increased with increasing levels of depression but not
      anxiety. This association between the MetS and depressive symptoms was
      independent of age, smoking status, socioeconomic factors, and lifestyle. The
      relationship was observed across body mass index categories and was independent
      of anxiety. CONCLUSIONS: The MetS is associated with depression and depressive
      symptoms but not anxiety irrespective of gender and overweight/obesity status in
      subjects at risk of cardiovascular disease. These findings suggest a potential
      importance of screening for depression in patients with the MetS.

PMID- 17553466
TI  - Erythropoietin reduces neural and cognitive processing of fear in human models of
      antidepressant drug action.
AB  - BACKGROUND: Erythropoietin (Epo) has neuroprotective and neurotrophic effects in
      animal models and affects cognitive and associated neural responses in humans.
      These effects have highlighted Epo as a candidate for treatment of psychiatric
      disease including schizophrenia and depression. The current study aimed to
      explore the effects of Epo on neural and behavioral measures of emotional
      processing relevant for depression and the effects of conventional antidepressant
      medication. METHODS: In the present study, we used functional magnetic resonance
      imaging to explore the effects of Epo (40,000 IU) versus saline on the neural
      processing of happy and fearful faces in 23 healthy volunteers. Facial expression
      recognition was assessed outside the scanner. RESULTS: One week after
      administration, Epo reduced neural response to fearful versus neutral faces in
      the occipito-parietal cortex consistent with reduced attention to fear.
      Erythropoietin additionally reduced recognition of fearful facial expressions
      without affecting recognition of other emotional expressions. These actions
      occurred in the absence of changes in hematological parameters. CONCLUSIONS: The
      present study demonstrates that Epo directly modulates brain responses to
      emotional information in humans in a manner consistent with the actions of
      conventional antidepressants. The characterization of the effects of Epo in a
      clinically depressed group is therefore warranted.

PMID- 17553467
TI  - A Randomized controlled trial of venlafaxine ER versus placebo in pediatric
      social anxiety disorder.
AB  - BACKGROUND: Social anxiety disorder, which occurs in 2% to 5% of children and
      adolescents, is associated with significant distress and functional impairment.
      METHODS: The objective of the randomized, masked controlled trial conducted in 48
      academic and community centers in the United States was to evaluate the efficacy
      of venlafaxine ER in children and adolescents with generalized social anxiety
      disorder. A volunteer sample of 293 outpatients, age 8 to 17, who met diagnostic
      criteria for social anxiety disorder and were enrolled between February 2000 and
      March 2003 participated. Venlafaxine ER or placebo was titrated from a starting
      dose of 37.5 mg to a maximum dose of 225 mg over 16 weeks. The primary dependent
      measures were the Social Anxiety Scale, child or adolescent version (SAS-CA) and
      for responder analysis, a (dichotomized) Clinical Global Impressions-Improvement
      (CGI-I) score. RESULTS: Compared with placebo, intent-to-treat random regression
      analyses indicated a statistically significant advantage for venlafaxine ER (p =
      .001) on the SAS-CA. On the CGI-I responder analysis, 56% (95% confidence
      interval [CI], 47%-64%) of venlafaxine ER treated subjects responded, which was
      statistically superior to placebo (37% [95% CI, 29%-45%]). Three venlafaxine ER
      and no placebo patients developed treatment-emergent suicidality; there were no
      completed suicides. CONCLUSIONS: Venlafaxine ER is an effective and reasonably
      well-tolerated treatment for generalized social anxiety disorder in children and
      adolescents. As with other antidepressants, careful clinical monitoring for
      adverse events, including treatment-emergent suicidality, is essential.

PMID- 17553468
TI  - Molecular mechanisms of vertebrate retina development: implications for ganglion
      cell and photoreceptor patterning.
AB  - Although the neural retina appears as a relatively uniform tissue when viewed
      from its surface, it is in fact highly patterned along its anterior-posterior and
      dorso-ventral axes. The question of how and when such patterns arise has been the
      subject of intensive investigations over several decades. Most studies aimed at
      understanding retinal pattern formation have used the retinotectal map, the
      ordered projections of retinal ganglion cells to the brain, as a functional
      readout of the pattern. However, other cell types are also topographically
      organized in the retina. The most commonly recognized example of such a
      topographic cellular organization is the differential distribution of
      photoreceptor types across the retina. Photoreceptor patterns are highly species
      specific and may represent an important adaptation to the visual niche a given
      species occupies. Nevertheless, few studies have addressed this functional
      readout of pattern to date and our understanding of its development has remained
      superficial. Here, we review recent advances in understanding the molecular
      cascades that control regionalization of the eye anlage, relate these findings to
      the development of photoreceptor patterns and discuss common and unique
      strategies involved in both aspects of retinal pattern formation.

PMID- 17553469
TI  - Immunolocalization of aquaporin-1 in the mechanoreceptive Ruffini endings in the
      periodontal ligament.
AB  - Previous ultrastructural studies have suggested an axon-Schwann cell interaction
      in the periodontal Ruffini ending, a primary mechanoreceptor. However, no
      information is available on the transport mechanism between them. The present
      study examined the immunolocalization of aquaporin-1 (AQP1) and -4 (AQP4), a
      member of the water-selective channel, in the periodontal Ruffini endings of the
      rat incisors and trigeminal ganglion. In addition, the expression of mRNA for
      AQP1 and 4 was detected in the trigeminal ganglion by a RT-PCR technique. A
      single PCR product of the sizes anticipated for AQP1 and 4 was detectable in a
      reverse transcripted cDNA sample from the trigeminal ganglion, whose neurons
      innervate the periodontal Ruffini endings. An AQP1 immunoreaction was
      recognizable in the axon terminals of the periodontal Ruffini endings as well as
      their associated terminal Schwann cells, as confirmed with a double staining with
      AQP1 and either PGP9.5 or S-100 protein. However, no immunoreaction for AQP4 was
      found in periodontal Ruffini endings. Although the AQP4 immunoreaction was
      localized in some satellite cells - but never in neurons - of the trigeminal
      ganglion, 16.1% trigeminal neurons showed the AQP1 immunoreaction. Furthermore,
      the AQP1 immunoreaction was found in certain satellite cells which surrounded
      AQP1-positive or -negative neurons. An analysis of a cross-sectional area of
      these positive neurons demonstrated that approximately 66.9% of the positive
      neurons were 400-1000 microm2 (671.4+/-172.4 microm2), indicating that they could
      be categorized as medium-sized neurons which mediate mechanotransduction. These
      findings suggest that AQP1 controls water transport in the periodontal Ruffini
      endings.

PMID- 17553470
TI  - The differential effects of 5-HT(1A) receptor stimulation on dopamine receptor
      mediated abnormal involuntary movements and rotations in the primed
      hemiparkinsonian rat.
AB  - Serotonin 1A receptor (5-HT(1A)R) agonists have emerged as valuable supplements
      to l-DOPA therapy, demonstrating that they can decrease side effects and enhance
      motor function in animal models of Parkinson's disease (PD) and human PD
      patients. The precise mechanism by which these receptors act remains unknown and
      there is limited information on how 5-HT(1A)R stimulation impacts striatal
      dopamine (DA) D1 receptor (D1R) and D2 receptor (D2R) function. The current study
      examined the effects of 5-HT(1A)R stimulation on DA receptor-mediated behaviors.
      Male Sprague-Dawley rats were rendered hemiparkinsonian by unilateral 6-OHDA
      lesions and primed with the D1R agonist SKF81297 (0.8 mg/kg, i.p.) in order to
      sensitize DA receptors. Using a randomized within subjects design, rats received
      a first injection of: Vehicle (dH(2)O) or the 5-HT(1A)R agonist +/-8-OH-DPAT (0.1
      or 1.0 mg/kg, i.p.), followed by a second injection of: Vehicle (dimethyl
      sulfoxide), the D1R agonist SKF81297 (0.8 mg/kg, i.p.), the D2R agonist
      quinpirole (0.2 mg/kg, i.p.), or l-DOPA (12 mg/kg+benserazide, 15 mg/kg, i.p.).
      On test days, rats were monitored over a 2-h period immediately following the
      second injection for abnormal involuntary movements (AIMs), analogous to
      dyskinesia observed in PD patients, and contralateral rotations. The present
      findings indicate that 5-HT(1A)R stimulation reduces AIMs induced by D1R, D2R and
      l-DOPA administration while its effects on DA agonist-induced rotations were
      receptor-dependent, suggesting that direct 5-HT(1A)R and DA receptor interactions
      may contribute to the unique profile of 5-HT(1A)R agonists for the improvement of
      PD treatment.

PMID- 17553471
TI  - Synthesis of deoxy and methoxy analogs of octyl alpha-D-mannopyranosyl-(1-->6)
      alpha-D-mannopyranoside as probes for mycobacterial lipoarabinomannan
      biosynthesis.
AB  - A panel of analogs of the disaccharide alpha-D-Manp-(1-->6)-alpha-D-Manp-OOctyl,
      a known acceptor substrate for a polyprenol monophosphomannose-dependent alpha-(1
      ->6)-mannosyltransferase involved in the assembly of the alpha-(1-->6)-linked
      mannan core of mycobacterial lipoarabinomannan, has been synthesized. Described
      are synthetic routes to the target deoxy and methoxy analogs in which one of the
      hydroxyl groups of the parent disaccharide has been modified. All glycosylation
      reactions involved the use of octyl glycoside acceptors and thioglycoside donors
      using iodonium-ion activation, and the stereochemistry of the mannopyranoside
      bond formed was established by measurement of the 1J(C-1,H-1). Depending on the
      target, the key methylation or deoxygenation reactions were carried out on either
      mono- or disaccharide substrates. This series of analogs will be useful for
      probing the substrate specificity of the enzyme, in particular, its steric and
      hydrogen-bonding requirements.

PMID- 17553472
TI  - Modification of methyl O-propargyl-D-glucosides: model studies for the synthesis
      of alkynyl based functional polysaccharides.
AB  - Methyl 4,6-O-benzylidene-2,3-di-O-propargyl-alpha-D-glucoside (2) has been
      prepared and its structure determined, including its X-ray structural analysis.
      For comparison the structure of the corresponding allyl derivative has also been
      determined by X-ray crystallography. Glucoside 2 is a versatile starting material
      for numerous novel derivatives such as diols, a diester, a diacid, and a
      dialdehyde. Subjecting 2 to a Mannich reaction leads to a (bis)amine in excellent
      yields. The click reaction between 2 and benzyl azide furnishes a (bis)triazole
      as the main product. Deprotection of 2 furnishes a (bis)propargyl ether, which
      can be converted by the methodology developed for 2 to the corresponding
      (bis)acetylenes; click reaction with benzyl azide converts 2 into a
      (bis)triazole.

PMID- 17553473
TI  - Synthesis of ketopyranosyl glycosides and determination of their anomeric
      configuration on the basis of the three-bond carbon-proton couplings.
AB  - Anomeric pairs of ketopyranosyl glycosides with various substituents at C(alpha),
      C(beta) and C(gamma) were synthesized from the corresponding thioglycosides, and
      the influence of the C(alpha)-C(beta)-C(gamma)-H(gamma) torsion angle and
      substituent effects on the three-bond carbon-proton couplings was studied. The
      cis coupling constants range from 1 to 2Hz. The trans couplings are generally as
      small as 2.3-2.6Hz; however, for compounds bearing an unsubstituted gamma-carbon,
      a relatively large trans coupling was measured (4.8Hz). An S-ethyl group at the
      beta-position increases the cis coupling (up to 3.2Hz) compared to the
      corresponding O-glycosides.

PMID- 17553474
TI  - Crystal structures of ethyl 3-azido-2,3-dideoxy-D-arabino-hexopyranoside anomers.
AB  - The structures of the title alpha (1) and beta (2) anomers of ethyl 3-azido-2,3
      dideoxy-d-arabino-exopyranoside (C(8)H(15)N(3)O(4)) are reported. The single
      crystal structures of C(8)H(15)N(3)O(4) were determined by X-ray crystallography
      at 293K. It has been found that both title compounds crystallize in the
      orthorhombic space group. In both cases, the unit cell contains four asymmetric
      molecules. From intensity measurements, it has been shown that each of these
      molecules adopts a (4)C(1) chair conformation. The packing arrangement in the
      unit cell displays a stratified structure. Moreover, medium strength O-H...O
      hydrogen bonds in both crystal lattices can be observed.

PMID- 17553475
TI  - Endothelial nitric oxide synthase promotes neonatal cardiomyocyte proliferation
      by inhibiting tissue inhibitor of metalloproteinase-3 expression.
AB  - OBJECTIVE: We have recently demonstrated that endothelial nitric oxide synthase
      (eNOS) promotes cardiomyocyte proliferation. However, mechanisms by which eNOS
      regulates cardiomyocyte proliferation are not fully understood. The goal of the
      present study was to investigate the role of tissue inhibitor of
      metalloproteinase-3 (TIMP-3) in eNOS-mediated cardiomyocyte proliferation.
      METHODS AND RESULTS: Experiments were conducted in cultured neonatal mouse
      cardiomyocytes. TIMP-3 expression was significantly decreased in wild-type (WT)
      cardiomyocytes treated with an adenoviral eNOS (Ad-eNOS). Furthermore, TIMP-3
      levels were significantly decreased in cardiomyocytes derived from eNOS
      transgenic mice. Conversely, TIMP-3 transcript levels were significantly elevated
      in eNOS(-/-) cardiomyocytes. The inhibitory effect of NO on TIMP-3 expression was
      dependent on S-nitrosylation of c-jun, a subunit of AP-1. Cell proliferation was
      increased in TIMP-3(-/-) cardiomyocytes while recombinant TIMP-3 decreased
      proliferation in both TIMP-3(-/-) and WT cardiomyocytes. Furthermore, the decline
      in proliferation observed in eNOS(-/-) cardiomyocytes was abrogated when TIMP-3
      expression was blocked by an anti-TIMP-3 antibody. In vivo cardiomyocyte
      proliferation was assessed by Ki67 immunostaining on postnatal day 1 hearts. Ki67
      positive cardiomyocytes were decreased in eNOS(-/-), but increased in eNOS-Tg and
      TIMP-3(-/-) hearts compared to WT controls. CONCLUSIONS: Our study suggests that
      eNOS promotes neonatal cardiomyocyte proliferation by inhibiting TIMP-3
      expression.

PMID- 17553477
TI  - Cyclization of natural allene oxide in aprotic solvent: formation of the novel
      oxylipin methyl cis-12-oxo-10-phytoenoate.
AB  - Allene oxide, (9Z,11E)-12,13-epoxy-9,11-octadecadienoic acid (12,13-EOD), was
      prepared by incubation of linoleic acid (13S)-hydroperoxide with flaxseed allene
      oxide synthase (AOS) and purified (as methyl ester) by low temperature HPLC.
      Identification of pure 12,13-EOD was substantiated by its UV and (1)H NMR spectra
      and by GC-MS data for its methanol trapping product. The methyl ester of 12,13
      EOD (but not the free carboxylic acid) is slowly cyclized in hexane solution,
      affording a novel cyclopentenone cis-12-oxo-10-phytoenoic acid. Free carboxylic
      form of 12,13-EOD does not cyclize due to the exceeding formation of macrolactone
      (9Z)-12-oxo-9-octadecen-11-olide. The spontaneous cyclization of pure natural
      allene oxide (12,13-EOD) into cis-cyclopentenone have been observed first time.

PMID- 17553476
TI  - Glucose phosphorylation is required for insulin-dependent mTOR signalling in the
      heart.
AB  - OBJECTIVE: Insulin regulates both glucose uptake and postnatal cardiac growth.
      The anabolic effects of insulin are mediated by the mammalian target of rapamycin
      (mTOR), an evolutionarily conserved kinase which is also a convergence point
      between nutrient sensing and cell growth. We postulated that mTOR signalling in
      the heart requires the metabolism of glucose. METHODS: We interrogated the
      insulin-mediated mTOR signalling pathway in response to different metabolic
      interventions regulating substrate metabolism in the isolated working rat heart
      and in isolated cardiomyocytes. RESULTS: Although insulin enhanced Akt activity,
      phosphorylation of mTOR and its downstream targets (p70S6K and 4EBP1) required
      the addition of glucose. Glucose-dependent p70S6K phosphorylation was independent
      of the hexosamine biosynthetic pathway, the AMP kinase pathway, and the pentose
      phosphate pathway. However, inhibition of glycolysis downstream of hexokinase
      markedly enhanced p70S6K phosphorylation. Furthermore, 2-deoxyglucose activated
      p70S6K suggesting that phosphorylation of glucose is required for carbohydrate
      mediated mTOR signalling in the heart. Lastly, we also found enhanced p70S6K
      phosphorylation in the hearts of diabetic rats. CONCLUSION: Phosphorylation of
      glucose is necessary for insulin-dependent mTOR activity in the heart, suggesting
      a link between intermediary metabolism and cardiac growth.

PMID- 17553478
TI  - Whole blood choline and plasma choline in acute coronary syndromes: prognostic
      and pathophysiological implications.
AB  - BACKGROUND: Whole blood choline (WBCHO) and plasma choline (PLCHO) concentrations
      increase rapidly after stimulation of phospholipase D in acute coronary syndromes
      (ACS). Early risk-stratification was analyzed in 217 patients with suspected ACS
      and a negative admission troponin T (<0.03 microg/L). METHODS: WBCHO and PLCHO
      were measured using high-performance-liquid-chromatography mass spectrometry.
      Major cardiac events (MACE) were defined as cardiac death/arrest, coronary
      intervention or myocardial infarction (MI). RESULTS: WBCHO (> or = 28.2
      micromol/L) was predictive for MACE (hazard ratio [HR] 2.7; p<0.001), cardiac
      death/arrest (HR 4.2; p=0.015), heart failure (HR 2.8; p=0.003), coronary
      intervention (HR 2.1; p=0.01) and MI (HR 8.4; p=0.002) after 30 days. PLCHO (> or
      = 25.0 micromol/L) was predictive for MACE (HR 2.6; p=0.005), cardiac
      death/arrest (HR 15.7; p<0.001), heart failure (HR 6.0; p<0.001) but not for
      coronary intervention and MI. WBCHO and PLCHO were predictive for MACE in
      multivariate analysis (Odds ratio [OR] 2.7, p=0.009 and OR 3.3, p=0.03)
      independently of age, gender, prior MI, coronary risk factors and ECG.
      CONCLUSIONS: WBCHO and PLCHO are significant and independent predictors of major
      cardiac events in admission troponin T negative acute coronary syndromes. Both
      are predictive for events related to tissue ischemia and WBCHO is capable of
      detecting risks associated with coronary plaque instability.

PMID- 17553479
TI  - A CBS haplotype and a polymorphism at the MSR gene are associated with
      cardiovascular disease in a Spanish case-control study.
AB  - OBJECTIVES: The aim of this study was to evaluate the association of
      polymorphisms present in genes related to homocysteine (Hcy) metabolism with
      coronary artery disease (CAD). DESIGN AND METHODS: We examined 8 polymorphisms in
      the cystathionine beta-synthase (CBS), glutamate carboxypeptidase II (GCPII),
      methionine synthase (MS), methionine synthase reductase (MSR) and
      methylenetetrahydrofolate reductase (MTHFR) genes in 140 CAD patients and 113
      controls, by means of Chi-square, logistic regression, ANOVA and the Mann-Whitney
      U test. RESULTS: The c.66 G allele of MSR conferred an odds-ratio for CAD of 1.76
      (95% CI 1.12-2.77), while a CBS haplotype [c.699C-c.844wt-c.1080C] was found over
      represented in CAD [OR of 2.16 (1.29-3.63)]. CONCLUSIONS: Our results not only
      highlight the involvement of the MSR and CBS genes in the etiology of
      cardiovascular disease, but also emphasize the strength of haplotype analyses in
      association studies.

PMID- 17553480
TI  - Calorimetric properties of water and triacylglycerols in fern spores relating to
      storage at cryogenic temperatures.
AB  - Storing spores is a promising method to conserve genetic diversity of ferns ex
      situ. Inappropriate water contents or damaging effects of triacylglycerol (TAG)
      crystallization may cause initial damage and deterioration with time in spores
      placed at -15 degrees C or liquid nitrogen temperatures. We used differential
      scanning calorimetry (DSC) to monitor enthalpy and temperature of water and TAG
      phase transitions within spores of five fern species: Pteris vittata, Thelypteris
      palustris, Dryopteris filix-mas, Polystichum aculeatum, Polystichum setiferum.
      The analyses suggested that these fern spores contained between 26% and 39% TAG,
      and were comprised of mostly oleic (P. vittata) or linoleic acid (other species)
      depending on species. The water contents at which water melting events were first
      observable ranged from 0.06 (P. vittata) to 0.12 (P. setiferum)gH(2)Og(-1)dry
      weight, and were highly correlated with water affinity parameters. In spores
      containing more than 0.09 (P. vittata) to 0.25 (P. setiferum)gH(2)Og(-1)dry
      weight, some water partitioned into a near pure water fraction that melted at
      about 0 degrees C. These sharp peaks near 0 degrees C were associated with lethal
      freezing treatments. The enthalpy of water melting transitions was similar in
      fern spores, pollen and seeds; however, the unfrozen water content was much lower
      in fern spores compared to other forms of germplasm. Though there is a narrow
      range of water contents appropriate for low temperature storage of fern spores,
      water content can be precisely manipulated to avoid both desiccation and freezing
      damage.

PMID- 17553481
TI  - Regeneration and maintenance of the planarian midline is regulated by a slit
      orthologue.
AB  - Several families of evolutionarily conserved axon guidance cues orchestrate the
      precise wiring of the nervous system during embryonic development. The remarkable
      plasticity of freshwater planarians provides the opportunity to study these
      molecules in the context of neural regeneration and maintenance. Here we
      characterize a homologue of the Slit family of guidance cues from the planarian
      Schmidtea mediterranea. Smed-slit is expressed along the planarian midline, in
      both dorsal and ventral domains. RNA interference (RNAi) targeting Smed-slit
      results in the collapse of many newly regenerated tissues at the midline; these
      include the cephalic ganglia, ventral nerve cords, photoreceptors, and the
      posterior digestive system. Surprisingly, Smed-slit RNAi knockdown animals also
      develop morphologically distinguishable, ectopic neural structures near the
      midline in uninjured regions of intact and regenerating planarians. These results
      suggest that Smed-slit acts not only as a repulsive cue required for proper
      midline formation during regeneration but that it may also act to regulate the
      behavior of neural precursors at the midline in intact planarians.

PMID- 17553482
TI  - Zscan4: a novel gene expressed exclusively in late 2-cell embryos and embryonic
      stem cells.
AB  - The first wave of transcription, called zygotic genome activation (ZGA), begins
      during the 2-cell stage in mouse preimplantation development and marks a vital
      transition from the maternal genetic to the embryonic genetic program. Utilizing
      DNA microarray data, we looked for genes that are expressed only during ZGA and
      found Zscan4, whose expression is restricted to late 2-cell stage embryos.
      Sequence analysis of genomic DNA and cDNA clones revealed nine paralogous genes
      tightly clustered in 0.85 Mb on mouse chromosome 7. Three genes are not
      transcribed and are thus considered pseudogenes. Among the six expressed genes
      named Zscan4a-Zscan4f, three - Zscan4c, Zscan4d, and Zscan4f - encode full-length
      ORFs with 506 amino acids. Zscan4d is a predominant transcript at the late 2-cell
      stage, whereas Zscan4c is a predominant transcript in embryonic stem (ES) cells.
      No transcripts of any Zscan4 genes are detected in any other cell types.
      Reduction of Zscan4 transcript levels by siRNAs delays the progression from the 2
      cell to the 4-cell stage and produces blastocysts that fail to implant or
      proliferate in blastocyst outgrowth culture. Zscan4 thus seems to be essential
      for preimplantation development.

PMID- 17553484
TI  - The immunomodulator FTY720 is phosphorylated and released from platelets.
AB  - The novel immunomodulator FTY720 causes lymphocytes from peripheral blood to
      accumulate in lymphoid tissues. In vivo, FTY720 is phosphorylated to FTY720-P,
      which binds to the sphingosine 1-phosphate receptor S1P(1). So far, it has been
      unclear where FTY720-P is produced. We demonstrate that platelets efficiently
      convert FTY720 to FTY720-P and release it into the extracellular space. This
      release is mostly independent of platelet activation, but is slightly increased
      upon thrombin stimulation. These results suggest that platelets are a major
      source of plasma FTY720-P, and that FTY720-P release is mediated by two different
      transporters.

PMID- 17553485
TI  - Combination of VEGF(165)/Angiopoietin-1 gene and endothelial progenitor cells for
      therapeutic neovascularization.
AB  - Previous studies have established that vascular endothelial growth factor (VEGF),
      Angiopoietin-1 (Ang1) and endothelial progenitor cells (EPCs) play important
      roles in neovascularization, suggesting that combination of them would be a
      promising therapy for ischemic diseases. So we constructed the adeno-associated
      virus-2 (AAV-2) vectors simultaneously encoding human VEGF(165) and Ang1 (AAV
      Ang1/VEGF), and investigated the combination therapeutic effect of AAV-Ang1/VEGF
      with EPCs in a rabbit ischemic hindlimb model. In the present study we found that
      AAV-Ang1/VEGF could successfully and efficiently transfer VEGF(165) and Ang1 gene
      into bone marrow derived EPCs for gene therapy. Combined administration of AAV
      Ang1/VEGF with EPCs had higher blood flow recovery, cellularity, capillary
      density and smooth muscle alpha-actin positive vessel density than administration
      of either of them alone. Furthermore, the strategy of pre-intramuscular injection
      of AAV-Ang1/VEGF followed by EPCs transplantation had a higher therapeutic effect
      than the strategy of transplantation of AAV-Ang1/VEGF transduced EPCs. It seemed
      that the former strategy may be a promising therapy for ischemic diseases.

PMID- 17553483
TI  - Spitz from the retina regulates genes transcribed in the second mitotic wave,
      peripodial epithelium, glia and plasmatocytes of the Drosophila eye imaginal
      disc.
AB  - Proliferation, differentiation, and other processes must be coordinated during
      the development of multi-cellular animals. A discrete and regulated cell
      division, the Second Mitotic Wave (SMW), occurs concomitantly with early cell
      fate decisions in the Drosophila developing retina. Signals from the Epidermal
      Growth Factor Receptor (EGFR) are required to promote cell cycle arrest of
      specified cells and antagonize S-phase entry in the SMW. Cells that do not
      receive any EGFR activity enter S-phase in the SMW in response to the Notch
      pathway. To identify genes with potential roles in the SMW, we used microarrays
      and genetic manipulation of the EGFR pathway to seek transcripts regulated during
      the SMW. RNA in situ hybridization of 126 differentially transcribed genes
      revealed genes that have novel expression patterns in cells closely associated
      with the SMW. In addition, other genes' transcripts were regulated in the
      differentiating photoreceptor cells, retinal basal glia, the peripodial
      epithelium and blood cells (plasmatocytes) associated with the developing retina.
      These novel targets suggest that during eye development, EGFR activity
      coordinates transcriptional programs in other tissues with retinal
      differentiation.

PMID- 17553487
TI  - Effect of S-diclofenac, a novel hydrogen sulfide releasing derivative, on
      carrageenan-induced hindpaw oedema formation in the rat.
AB  - S-diclofenac (2-[(2,6-dichlorophenyl)amino]benzeneacetic acid 4-(3H-1,2-dithiole
      3-thione-5-yl)-phenyl ester) is a novel derivative of diclofenac which, in vivo,
      undergoes enzymatic cleavage of its ester linkage to release hydrogen sulfide
      (H(2)S) along with the parent moiety, diclofenac. In this study the anti
      inflammatory activity of S-diclofenac and diclofenac was studied in a carrageenan
      evoked hindpaw oedema model in the rat. Drugs or vehicle were administered 3 h
      before carrageenan. Both drugs produced a dose-dependent anti-inflammatory effect
      in this model. However, S-diclofenac (ED(30), 14.2+/-0.6 micromol/kg) was more
      potent (P<0.05) than diclofenac (ED(30), 39.3+/-1.4 micromol/kg) as an inhibitor
      both of hindpaw swelling and in reducing the carrageenan-evoked rise in hindpaw
      myeloperoxidase activity reflecting tissue neutrophil infiltration (ED(50)s of
      12.0+/-2.1 micromol/kg and 21.9+/-2.0 micromol/kg). Intraplantar carrageenan
      injection also significantly (P<0.05) increased hindpaw concentrations of
      prostaglandin E(2) (PGE(2)), nitrite/nitrate and H(2)S synthesizing activity
      measured at 6 h. Both S-diclofenac and diclofenac pretreatment reduced the
      carrageenan-induced rise in hindpaw PGE(2), nitrite/nitrate and H(2)S
      synthesizing activity. Whilst treatment with either drug produced similar
      inhibition of hindpaw PGE(2) and H(2)S synthesizing activity--S-diclofenac more
      effectively reduced hindpaw nitrite/nitrate concentration than did diclofenac. It
      is proposed that the enhanced anti-inflammatory effect of S-diclofenac relates to
      its ability to release H(2)S at the inflamed site. These data provide evidence
      for an anti-inflammatory effect of H(2)S.

PMID- 17553486
TI  - Differences in the relative potency of SR 141716A and AM 251 as antagonists of
      various in vivo effects of cannabinoid agonists in C57BL/6J mice.
AB  - Although the cannabinoid CB(1) antagonist N-(piperidin-1-yl)-5-(4-chlorophenyl)-1
      (2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (SR 141716A) blocks many
      of the in vivo effects of cannabinoids, the antagonist activity of SR 141716A is
      limited under some conditions. The general aims of this study were to: 1) examine
      whether the limited antagonist activity of SR 141716A generalizes to the
      cannabinoid CB(1) antagonist N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4
      dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (AM 251); and 2) examine
      mechanisms by which cannabinoids produce hypothermia, catalepsy, and hypoactivity
      in C57BL/6J mice. SR 141716A and AM 251 were administered alone and in
      combination with the cannabinoid agonists triangle up(9)-tetrahydrocannabinol
      (triangle up(9)-THC) and R-(+)-[2,3-dihydro-5-methyl-3-[(morpholinyl)
      methyl]pyrrolol-[1,2,3-de]-1,4-benzoxazinyl]-(1-naphthalenyl) methanone (WIN
      55212-2). triangle up(9)-THC and WIN 55212-2 produced catalepsy, hypothermia, and
      hypoactivity with similar potency; WIN 55212-2 produced greater hypothermia than
      triangle up(9)-THC, otherwise differences in maximal effect were not detected in
      the other assays. When administered alone, the antagonists did not produce
      catalepsy or alter body temperature and they decreased locomotor activity. SR
      1417167A and AM 251 blocked catalepsy and hypothermia, and partially attenuated
      hypoactivity, produced by triangle up(9)-THC and WIN 55212-2. While the
      antagonists were equipotent in blocking agonist-induced hypothermia, SR 141716A
      was 6-fold more potent than AM 251 in blocking agonist-induced catalepsy. The
      results demonstrate that SR 141716A and AM 251 have strikingly similar behavioral
      activity, i.e., they block some and not other in vivo effects of cannabinoid
      agonists, and further demonstrate differences in the maximum effect of
      cannabinoid agonists that might be related to differences in agonist efficacy.
      While the results strongly suggest that cannabinoid CB(1) receptors mediate the
      hypothermic and cataleptic effects of cannabinoids, differences in the relative
      potency of antagonists suggest that mechanisms responsible for these effects are
      not identical.

PMID- 17553488
TI  - Correlation of the feline PKD1 genetic mutation with cases of PKD diagnosed by
      pathological examination.
AB  - Autosomal-dominant polycystic kidney disease (AD-PKD) is the most prevalent
      inherited genetic disease of cats, particularly affecting Persians. Using
      archived tissue samples from 44 cats a genotype was successfully obtained by real
      time PCR for 43 cats. Twenty-five cats (18 Persians, 4 domestic longhair cats and
      3 domestic shorthair (DSH) cats) were found to carry the AD-PKD mutation and all
      of these cats had macroscopic and/or microscopic evidence of renal cysts
      consistent with PKD. Eighteen cats were found to be wild-type. Twelve of these
      (all Persians) had no pathological evidence of PKD, but the remaining 6 cats had
      evidence of renal cystic lesions. On pathological review the cystic lesions in 4
      (2 Persians and 2 DSH) of these 6 cats were considered not to be consistent with
      a primary diagnosis of PKD. Histological evidence of polycystic kidneys was,
      however, confirmed in the remaining 2 cats (1 DSH and 1 Bengal) and may indicate
      that other PKD-causing mutations exist in the feline population.

PMID- 17553489
TI  - Mutants in the Dictyostelium Arp2/3 complex and chemoattractant-induced actin
      polymerization.
AB  - We have investigated the role of the Arp2/3 complex in Dictyostelium cell
      chemotaxis towards cyclic-AMP and in the actin polymerization that is triggered
      by this chemoattractant. We confirm that the Arp2/3 complex is recruited to the
      cell perimeter, or into a pseudopod, after cyclic-AMP stimulation and that this
      is coincident with actin polymerization. This recruitment is inhibited when actin
      polymerization is blocked using latrunculin suggesting that the complex binds to
      pre-existing actin filaments, rather than to a membrane associated signaling
      complex. We show genetically that an intact Arp2/3 complex is essential in
      Dictyostelium and have produced partially active mutants in two of its subunits.
      In these mutants both phases of actin polymerization in response to cyclic-AMP
      are greatly reduced. One mutant projects pseudopodia more slowly than wild type
      and has impaired chemotaxis, together with slower movement. The second mutant
      chemotaxes poorly due to an adhesion defect, suggesting that the Arp2/3 complex
      plays a crucial part in adhering cells to the substratum as they move. We
      conclude that the Arp2/3 complex largely mediates the actin polymerization
      response to chemotactic stimulation and contributes to cell motility, pseudopod
      extension and adhesion in Dictyostelium chemotaxis.

PMID- 17553490
TI  - Inhibitors of phosphoinositide 3-kinase cause defects in the postendocytic
      sorting of beta2-adrenergic receptors.
AB  - Phosphatidylinositol 3-kinase inhibitors have been shown to affect endocytosis or
      subsequent intracellular sorting in various receptor systems. Agonist-activated
      beta(2)-adrenergic receptors undergo desensitization by mechanisms that include
      the phosphorylation, endocytosis and degradation of receptors. Following
      endocytosis, most internalized receptors are sorted to the cell surface, but some
      proportion is sorted to lysosomes for degradation. It is not known what governs
      the ratio of receptors that recycle versus receptors that undergo degradation. To
      determine if phosphatidylinositol 3-kinases regulate beta(2)-adrenergic receptor
      trafficking, HEK293 cells stably expressing these receptors were treated with the
      phosphatidylinositol 3-kinase inhibitors LY294002 or wortmannin. We then studied
      agonist-induced receptor endocytosis and postendocytic sorting, including
      recycling and degradation of the internalized receptors. Both inhibitors
      amplified the internalization of receptors after exposure to the beta-agonist
      isoproterenol, which was attributable to the sorting of a significant fraction of
      receptors to an intracellular compartment from which receptor recycling did not
      occur. The initial rate of beta(2)-adrenergic receptor endocytosis and the
      default rate of receptor recycling were not significantly altered. During
      prolonged exposure to agonist, LY294002 slowed the degradation rate of beta(2)
      adrenergic receptors and caused the accumulation of receptors within rab7
      positive vesicles. These results suggest that phosphatidylinositol 3-kinase
      inhibitors (1) cause a misrouting of beta(2)-adrenergic receptors into vesicles
      that are neither able to efficiently recycle to the surface nor sort to
      lysosomes, and (2) delays the movement of receptors from late endosomes to
      lysosomes.

PMID- 17553491
TI  - Interleukin-13 interferes with CFTR and AQP5 expression and localization during
      human airway epithelial cell differentiation.
AB  - Interleukin-13 (IL-13) is a central regulator of Th2-dominated respiratory
      disorders such as asthma. Lesions of the airway epithelial barrier frequently
      observed in chronic respiratory inflammatory diseases are repaired through
      proliferation, migration and differentiation of epithelial cells. Our work is
      focused on the effects of IL-13 in human cellular models of airway epithelial
      cell regeneration. We have previously shown that IL-13 altered epithelial cell
      polarity during mucociliary differentiation of human nasal epithelial cells. In
      particular, the cytokine inhibited ezrin expression and interfered with its
      apical localization during epithelial cell differentiation in vitro. Here we show
      that CFTR expression is enhanced in the presence of the cytokine, that two
      additional CFTR protein isoforms are expressed in IL-13-treated cells and that
      part of the protein is retained within the endoplasmic reticulum. We further show
      that aquaporin 5 expression, a water channel localized within the apical membrane
      of epithelial cells, is completely abolished in the presence of the cytokine.
      These results show that IL-13 interferes with ion and water channel expression
      and localization during epithelial regeneration and may thereby influence mucus
      composition and hydration.

PMID- 17553492
TI  - Distribution and composition of esterified and unesterified cholesterol in extra
      macular drusen.
AB  - More details about the distribution of esterified and unesterified cholesterol
      (EC, UC), abundant druse components, would inform models of druse biogenesis and
      new technologies for ocular imaging. From donors with grossly normal maculas
      (n=10, 66-86years), whose eyes were preserved in paraformaldehyde within 6h of
      death, extra-macular drusen encased with retinal pigment epithelium (RPE) were
      isolated manually. Cryosections of pelleted drusen, stained with filipin for UC
      and EC, were used to investigate filipin staining patterns within single drusen
      (n=193) and to quantify fluorescence (n=146). From lipid extracts of other
      drusen/RPE and RPE samples, total cholesterol (TC) and UC were determined by
      enzymatic fluorimetry. Drusen contained cores, basally located regions that were
      intensely bright when stained for UC or deeply dark when stained for EC; many
      were surrounded by concentric lamellae. Within the same cores, the EC-poor
      regions were significantly smaller (13.0mum) than UC-rich regions (17.1mum).
      Drusen with highly fluorescent EC-rich shells lacked UC-rich shells. Small spots
      representing lakes were visible only in drusen stained for EC. Some drusen had
      small, refractive spherical inclusions lacking both UC and EC. Of drusen
      examined, 32% had a UC-rich core, 35% had an EC-poor core, 31% had an EC-rich
      shell, 25% had EC-rich lakes, and 4-5% had UC-, EC-poor inclusions. Shells and
      cores occurred in significantly non-overlapping druse populations. The percentage
      of TC that was esterified ranged from 32-66% for drusen/RPE and 5-21% for RPE.
      The disposition of cholesterol in cores may reflect the activity of invading
      cellular process. The greater size of UC-rich cores relative to EC-poor cores may
      reflect a declining gradient of enzymatic activity with increased radial distance
      from the putative invaders. The relative sizes of sub-domains defined by
      cholesterol composition are compared to sub-domains detected in drusen by in vivo
      imaging methods.

PMID- 17553493
TI  - Glucocorticoid modulation of neuronal activity and hormone secretion induced by
      blood volume expansion.
AB  - The present study evaluated the involvement of glucocorticoid in the activation
      of vasopressinergic and oxytocinergic neurons of hypothalamic nuclei and plasma
      levels of vasopressin (AVP), oxytocin (OT), atrial natriuretic peptide (ANP) and
      corticosterone (CORT) in response to both isotonic and hypertonic blood volume
      expansion (BVE). Rats were subjected to isotonic (0.15 M NaCl, 2 ml/100 g b.w.,
      i.v.) or hypertonic (0.30 M NaCl, 2 ml/100 g b.w., i.v.) BVE with or without pre
      treatment with dexamethasone (1 mg/kg, i.p.). Results showed that isotonic BVE
      increased OT, ANP and CORT, and decreased AVP plasma levels. On the other hand,
      hypertonic BVE enhanced AVP, ANP, OT, and CORT plasma concentrations. Both
      hypertonic and isotonic BVE induced an increase in the number of Fos-OT double
      labeled magnocellular neurons in the PVN and SON. Pre-treatment with
      dexamethasone reduced OT secretion, as well as Fos-OT immunoreactive neurons in
      response to both isotonic and hypertonic BVE. We also observed that dexamethasone
      pre-treatment had no effect on AVP secretion in response to hypertonic BVE,
      although this effect was associated with a blockade of Fos expression in the
      vasopressinergic magnocellular neurons in the PVN and SON. In conclusion, these
      data suggest that, not only the rapid OT release from storages, but also the
      oxytocinergic cellular activation induced by BVE are modulated by
      glucocorticoids. However, this pattern of response was not observed for AVP
      cells, suggesting that dexamethasone is not likely to influence rapid release of
      AVP but seems to modulate the activation of these neurons in response to
      hypertonic BVE.

PMID- 17553494
TI  - Tyrosine kinase and cooperative TGFbeta signaling in the reproductive organs of
      Schistosoma mansoni.
AB  - Drug-induced suppression of female schistosome sexual maturation is an auspicious
      strategy to combat schistosomiasis since the eggs are the causative agent. The
      establishment of drug targets requires knowledge about the molecular mechanisms
      that regulate the development of the female reproductive organs, which include
      vitellarium and ovary. This review summarizes recent studies suggesting tyrosine
      kinases as important factors for the regulation of female gonad development. In
      this context, especially cytoplasmatic tyrosine kinases of the Src class seem to
      play dominant roles. Moreover, experimental data and theoretical concepts are
      provided supporting a crosstalk between tyrosine kinase and TGFbeta signaling in
      the production of vitellocytes. Finally, we take advantage from the schistosome
      genome project to propose a model for the regulation of vitelline-cell production
      and differentiation.

PMID- 17553495
TI  - The trichomonad cysteine proteinase TVCP4 transcript contains an iron-responsive
      element.
AB  - The differential expression of the Trichomonas vaginalis cysteine proteinase
      TVCP4 by iron at the protein synthesis level and the prediction of an iron
      responsive element (IRE)-like stem-loop structure at the 5'-region of the T.
      vaginalis cysteine proteinase 4 gene (tvcp4) mRNA suggest a post-transcriptional
      mechanism of iron regulation in trichomonads mediated by an IRE/IRP-like system.
      Gel-shifting, UV cross-linking and competition experiments demonstrated that this
      IRE-like structure specifically bound to human iron regulatory protein-1. IRP
      like cytoplasmic proteins that bound human ferritin IRE sequence transcripts at
      low-iron conditions were also found in trichomonads. Thus, a post-transcriptional
      regulatory mechanism by iron for tvcp4 mediated by IRE/IRP-like interactions was
      found.

PMID- 17553496
TI  - Tight junction modulation and biochemical characterisation of the zonula
      occludens toxin C-and N-termini.
AB  - The ZOT N-terminal domain was expressed and refolded, yielding a soluble protein
      with defined secondary structure. Although distantly related to protein I of
      filamentous phages, no evidence of ATPase activity was found. It is therefore
      unlikely that the ZOT N-terminal domain is involved in cholera toxin phage
      packaging in Vibrio cholerae. The ZOT C-terminal domain caused delocalisation of
      occludin and ZO-1 from Caco-2 cell-cell contacts, irrespective of disulfide
      bridge formation in its putative binding domain. However, the C-terminal domain
      did not cause actin reorganisation and this may explain the absence of a
      concomitant reduction in the transepithelial electrical resistance across cell
      monolayers.

PMID- 17553497
TI  - Generation of cell lines with tetracycline-regulated autophagy and a role for
      autophagy in controlling cell size.
AB  - Autophagy is an intracellular bulk degradation system. We established mouse
      fibroblast lines coupling the Tet-off system with an Atg5-/- mouse embryonic
      fibroblast line to artificially regulate autophagic ability. In the presence of
      doxycycline (Dox), Atg5 expression was completely suppressed and these cells were
      autophagy-defective. After removal of Dox, autophagic ability was restored within
      6 h. Very low levels of Atg5 could induce an autophagy competent state. We
      applied this novel system to examine the contribution of autophagy to controlling
      cell size. Cell size reduction in response to starvation was significantly
      inhibited in cells unable to undergo autophagy. The generated cell lines will be
      useful reagents for future mechanistic studies into the regulation and
      physiologic significance of autophagy.

PMID- 17553498
TI  - Short-term sensitization of colon mechanoreceptors is associated with long-term
      hypersensitivity to colon distention in the mouse.
AB  - BACKGROUND & AIMS: Using a mouse model that reproduces major features of
      irritable bowel syndrome (long-lasting colon hypersensitivity without
      inflammation), we examined the contributions of 2 proteins, transient receptor
      potential vanilloid 1 (TRPV1) and acid-sensing ion channel 3 (ASIC3), on
      development of behavioral hypersensitivity and assessed the function of colon
      mechanoreceptors of hypersensitive mice. METHODS: Visceral nociceptive behavior
      was measured as the visceromotor response (VMR) to colorectal distention (CRD)
      before and after intracolonic treatment with zymosan or saline. Colon pathology
      was assessed in parallel experiments by quantifying myeloperoxidase activity,
      intralumenal pH, and tissue histology. Electrophysiologic experiments were
      performed on naive and zymosan-treated hypersensitive mice using an in vitro
      colon-pelvic nerve preparation. RESULTS: Zymosan, but not saline, produced
      significant and persistent increases in the VMRs of control mice; zymosan
      produced nonsignificant increases in the VMRs in TRPV1 and ASIC3 knockout mice.
      Colon myeloperoxidase activity and pH were unaffected by either CRD or
      intracolonic treatments. Pelvic nerve mechanoreceptors recorded from zymosan
      treated or naive mice had similar sensitivity to stretch of the colon. When
      applied acutely, zymosan sensitized muscular/mucosal mechanoreceptors in both
      naive and hypersensitive mice. CONCLUSIONS: Zymosan produced sensitization of
      colon mechanoreceptors acutely in vitro and chronic (>or=7 weeks) behavioral
      hypersensitivity in the absence of inflammation. The behavioral hypersensitivity
      was partially dependent on both TRPV1 and ASIC3 because deletions of either of
      these genes blunted zymosan's effect, suggesting that these proteins may be
      important peripheral mediators for development of functional (ie,
      noninflammatory) visceral hypersensitivity.

PMID- 17553499
TI  - Acute effects of neurosteroids in a rodent model of primary paroxysmal dystonia.
AB  - The pathophysiology of various types of dyskinesias, including dystonias, is
      poorly understood. Clinical and epidemiological studies in humans revealed that
      the severity of dyskinesias and the frequency of paroxysmal forms of the disease
      are altered by factors such as the onset of puberty, pregnancy, cyclical changes
      and stress, indicating an underlying hormonal component. The dystonic phenotype
      in the dt(sz) hamster, a genetic animal model of paroxysmal dystonia, has been
      suggested to be based on a deficit of striatal gamma-aminobutyric acid
      (GABA)ergic interneurons and changes in the GABA(A) receptor complex. In this
      animal model, hormonal influences seem to be also involved in the
      pathophysiology, but an influence of peripheral sex hormones has already been
      excluded. Possibly, neurosteroids as endogenous regulators of the GABA(A)
      receptor may be critically involved in the pathophysiology of dystonia in this
      animal model. Therefore, in the present study, the effects of the neurosteroids
      allopregnanolone acetate and allotetrahydrodeoxycorticosterone (THDOC),
      representing positive modulators of the GABA(A) receptor, as well as of the
      negative GABA(A) receptor modulators pregnenolone sulfate and
      dehydroepiandrosterone (DHEA), on severity of dystonia were examined in dt(sz)
      hamsters after acute intraperitoneal injections. Allopregnanolone acetate and
      THDOC exerted a moderate reduction of dystonia, whereas pregnenolone sulfate and
      DHEA had no significant effects. Although the effects of allopregnanolone acetate
      and THDOC were moderate and short-lasting, the present results suggest that
      changes in neurosteroid levels might be involved in the initiation of dystonic
      episodes. Future studies have to include measurements of brain neurosteroid
      levels as well as of chronic neurosteroid administrations to clarify the
      pathophysiological role and therapeutic potential of neurosteroids in dystonia.

PMID- 17553500
TI  - Sex and drugs: comment on "Evidence for involvement of erbeta and rgs9-2 in 17
      beta estradiol enhancement of amphetamine-induced place preference behavior" by
      Silverman and Koenig.

PMID- 17553501
TI  - Increases in plasma corticosterone and stretched-attend postures in rats naive
      and previously exposed to the elevated plus-maze are sensitive to the anxiolytic
      like effects of midazolam.
AB  - A single exposure to the elevated plus-maze test (EPM) reduces or abolishes the
      anxiolytic efficacy of benzodiazepines on a second trial. This phenomenon known
      as one-trial tolerance (OTT) is considered to be due to a shift in the emotional
      state of the animals across the test/retest sessions. Activation of the
      hypothalamic-pituitary-adrenocortical (HPA) axis has been considered to be an
      adaptive response to stressful or challenging situations such as height and
      openness of the EPM. This work looks at the phenomenon of OTT to the
      benzodiazepine compound midazolam through the conjoint examination of the novel
      ethological measures of the EPM and adrenocortical response of rats exposed to
      single and repeated sessions of the EPM. The results obtained confirmed that the
      approach/avoidance conflict on the first trial of the EPM is very sensitive to
      the anxiolytic effects of benzodiazepines. Moreover, stressful stimuli present
      upon initial exposure to the EPM render the standard measures of the EPM
      resistant to the anxiolytic effects of benzodiazepines on retest. However, the
      increases in plasma corticosterone and in risk assessment behavior observed in
      rats submitted to single or repeated sessions in the EPM were reversed by
      pretreatment with midazolam. The administration of metyrapone, a glucocorticoid
      synthesis blocker, decreased risk assessment but did not affect locomotion and
      anxiety-like behaviors. It is suggested that the detection of the dangerous
      environment through the stretched-attend postures in the second trial leads to
      the known low level of exploration and the consequent OTT upon retest. Moreover,
      in view of the similarity between the risk assessment and plasma corticosterone
      patterns in both naive and experienced rats, this hormone-behavior profile may be
      crucial for the expression of OTT to benzodiazepines in rodents exposed to the
      EPM.

PMID- 17553503
TI  - The effectiveness of massage with and without dimethyl sulfoxide in preventing
      pressure ulcers: a randomized, double-blind cross-over trial in patients prone to
      pressure ulcers.
AB  - BACKGROUND: Although guidelines advise against massage, it is one of the methods
      widely regarded and used by nurses to prevent pressure ulcers (PU). OBJECTIVES:
      The purpose of this study was to examine the effectiveness of different
      variations of massage in preventing pressure ulcers. METHODS: A randomized,
      double-blind cross-over design, in which patients of nursing homes who are prone
      to PU underwent two of the three possible interventions; 'position changes only',
      'massaging with an indifferent cream' and 'massaging with a dimethyl sulfoxide
      (DMSO) cream'. RESULTS: The results of three interventions did not differ
      significantly. DMSO did not fulfil the expectations raised by literature and a
      previous pilot-study.

PMID- 17553502
TI  - Oxytocin has dose-dependent developmental effects on pair-bonding and
      alloparental care in female prairie voles.
AB  - The present study examines the developmental consequences of neonatal exposure to
      oxytocin on adult social behaviors in female prairie voles (Microtus
      ochrogaster). Female neonates were injected within 24 h of birth with isotonic
      saline or one of four dosages of oxytocin (OT). As adults, females were tested in
      an elevated plus-maze paradigm (a measure of anxiety and exploratory behavior),
      and for alloparental behavior and partner preferences. At 2 mg/kg OT, females
      took longer to approach pups, but were the only group to form a statistically
      significant within-group partner preference. At 4 mg/kg OT, females retrieved
      pups significantly more frequently but no longer displayed a partner preference;
      while females treated developmentally with 8 mg/kg spent significantly more time
      in side-to-side contact with a male stranger than any other treatment group. OT
      may have broad developmental consequences, but these effects are not linear and
      may both increase and decrease the propensity to display behaviors such as pair
      bonding.

PMID- 17553504
TI  - Sub-chronic nicotine exposure induces intercellular communication failure and
      differential down-regulation of connexins in cultured human endothelial cells.
AB  - BACKGROUND: Tobacco abuse is still among the most important cardiovascular risk
      factors in modern society. We investigated whether sub-chronic nicotine exposure
      can induce endothelial dysfunction and communication failure. METHODS AND
      RESULTS: Primary human umbilical vein endothelial cells (HUVEC) were cultured
      with or without 1 microM nicotine given for the entire cell culture passage until
      confluence (5+/-0.5 days). Cells were cultured on special Petri dishes consisting
      of two compartments which communicated only via a small cellular bridge. We
      determined the propagation of the NO signal after stimulation of compartment A
      with ATP by simultaneous spectrophotometric measurement of ATP and methemoglobin
      formation indicating NO release in compartment B. In HUVECs grown under nicotine
      we found significantly reduced NO formation in compartment B 5 min after ATP
      stimulation of compartment A. At that time, there was no ATP detectable in
      compartment B. The difference in NO-signal-propagation could be abolished with
      the gap junction blocker Na-propionate. Western blot and immunohistochemistry
      indicated significantly reduced levels of endothelial gap junction proteins Cx37
      and Cx43, but not Cx40. Dye transfer experiments revealed reduced number of
      communicating cells in nicotine exposed cells indicating the functional
      relevance. CONCLUSIONS: These results - for the first time - show that nicotine
      induces functional intercellular communication failure in endothelial cells
      probably resulting from down-regulated Cx37 and Cx43 expression.

PMID- 17553505
TI  - Insulin-inhibited and stimulated cultured vascular smooth muscle cell migration
      are related to divergent effects on protein phosphatase-2A and autonomous
      calcium/calmodulin-dependent protein kinase II.
AB  - Insulin, in the permissive presence of nitric oxide (NO), stimulates cGMP
      production which inhibits autonomous calcium/calmodulin-dependent protein kinase
      II (CaM kinase II) thereby inhibiting cultured vascular smooth muscle cell (VSMC)
      migration. In the presence of angiotensin II (Ang II), insulin stimulates NAD(P)H
      oxidase activity leading to increased VSMC migration. We wished to see whether
      insulin-stimulated cGMP stimulates protein phosphatase-2A (PP-2A) thereby
      inhibiting autonomous CaM kinase II and migration, and whether insulin, in the
      presence of Ang II, inhibits PP-2A and stimulates autonomous CaM kinase II in a
      NAD(P)H oxidase-dependent manner. One nanomole per litre of insulin in the
      presence of NO, or 50 micromol/L 8-Br-cGMP stimulated PP-2A activity by 46+/-6
      and 247+/-23%, respectively (both P<0.05), and 8-Br-cGMP inhibited autonomous CaM
      kinase II activity by 67+/-9% (P<0.05) by a 10 nmol/L okadaic acid-sensitive
      pathway. Insulin plus Ang II inhibited PP-2A activity by 57+/-7% (P<0.05) and
      stimulated autonomous CaM kinase II activity by 120+/-14% (P<0.05), both by an
      apocynin-sensitive pathway. 8-Br-cGMP-inhibited VSMC migration was blocked by
      okadaic acid. It is concluded that insulin in the presence of NO stimulates cGMP
      which stimulates PP-2A activity causing inhibition of autonomous CaM kinase II
      activity and thus VSMC migration, and that insulin in the presence of Ang II
      inhibits PP-2A and stimulates autonomous CaM kinase II activities by a NAD(P)H
      oxidase-dependent mechanism which are associated with insulin-stimulated NAD(P)H
      oxidase-dependent migration.

PMID- 17553506
TI  - Fatty acid binding protein 4 is increased in metabolic syndrome and with
      thiazolidinedione treatment in diabetic patients.
AB  - OBJECTIVE: To study the role of FABP4 in the plasma of type 2 diabetic (T2D)
      subjects with and without metabolic syndrome (MS) and the impact of
      thiazolidinedione (TZD) treatment. METHODS AND RESULTS: FABP4 was analyzed in 274
      individuals (169 T2D subjects and 105 controls). MS-T2D subjects had higher FABP4
      levels than non-MS-T2D subjects and controls (53% and 76% increase, respectively,
      p<0.005). FABP4 levels in T2D subjects were positively correlated to the number
      of MS elements, obesity degree, adiponectin, triglycerides, lipoperoxides, C
      reactive protein, age, systolic blood pressure and diabetes duration (p<0.05).
      Neither clinical or subclinical atherosclerosis, nor plasma levels of insulin,
      glucose or RBP4 were associated to FABP4. TZD-treated T2D subjects showed >30%
      higher FABP4 levels (p<0.05) than non-TZD-treated T2D. A subgroup study confirmed
      that TZD treatment prospectively increased FABP4 levels (p<0.05) along with an
      increase of peripheral blood mononuclear cell PPARgamma activity (p<0.05).
      Furthermore, in vitro studies showed that TZD treatment increased FABP4 mRNA,
      intracellular protein levels and extracellular secretion from human adipocytes.
      CONCLUSIONS/INTERPRETATION: FABP4 plasma concentrations are increased with the
      early presence of MS components, as well as inflammation and oxidation markers in
      T2D subjects. TZD increases FABP4 plasma concentrations, reflecting PPARgamma
      activation. FABP4 plasma measurements could be useful in the management of T2D
      subjects.

PMID- 17553507
TI  - Low phospholipid transfer protein (PLTP) is a risk factor for peripheral
      atherosclerosis.
AB  - OBJECTIVE: Phospholipid transfer protein (PLTP) facilitates cholesterol efflux
      from cells, intravascular HDL remodelling and transfer of vitamin E and
      endotoxin. In humans, the relationship of PLTP to atherosclerosis is unknown.
      However, strong coronary risk factors like obesity, diabetes, cigarette smoking
      and inflammation increase circulating levels of active PLTP. The aim of the
      present, cross-sectional study was to analyze the relationship of PLTP to
      peripheral arterial disease, a marker of generalized atherosclerosis,
      independently of potentially confounding factors like obesity, diabetes and
      smoking. METHODS: We performed a case control study in 153 patients with
      symptomatic peripheral arterial disease (PAD) and 208 controls free of vascular
      disease. Smokers and patients with diabetes mellitus were excluded. A lipoprotein
      independent assay was used for measurement of circulating bioactive PLTP and an
      ELISA utilizing a monoclonal antibody was used to analyze PLTP mass. RESULTS:
      PLTP activity was significantly decreased in patients with PAD 5.5 (4.6
      6.4)(median (25th-75th percentile)) versus 5.9 (5.1-6.9) micromol/mL/h in
      controls (p=0.001). In contrast, PLTP mass was similar in patients with PAD 8.5
      microg/mL (7.3-9.5) and in controls 8.3 microg/mL (6.9-9.7) (p=0.665).
      Multivariate logistic regression analysis revealed that PLTP activity is
      independently associated with the presence of PAD. PLTP activity was similar in
      patients with and without lipid-lowering drugs (p=0.396). CONCLUSION: Our results
      show that in non-diabetic, non-smoking subjects low rather than high PLTP
      activity is a marker for the presence of peripheral arterial disease and that
      distribution of PLTP between high-activity and low-activity forms may be
      compromised in atherosclerosis.

PMID- 17553508
TI  - Associations of carotid intima-media thickness, tobacco smoking and overweight
      with hearing disorder in a general population sample.
AB  - It has been argued that smoking or overweight might contribute to hearing
      disorder by atherogenic narrowing of the nutrient arteries to the cochlea. The
      carotid intima-media thickness (CIMT) is a surrogate marker for generalized
      atherosclerosis. We analyzed a subgroup (n=2619) from a general population sample
      in north-eastern Germany aged 45-81 years (Study of Health in Pomerania, SHIP).
      Assessments included self-statements about hearing disorder and medical
      examinations of CIMT. Using ordinal logistic regression for data analysis and
      after adjustment for cigarettes per day, waist circumference, diabetes, exposure
      to noise, age and sex, we found CIMT remained a predictor of hearing disorder
      (odds ratio 1.8, 95% confidence interval 1.0-3.2). Cigarettes per day and waist
      circumference were related to CIMT but not to hearing disorder. The findings
      suggest a positive association between CIMT and hearing disorder.

PMID- 17553509
TI  - Engineering tubular bone constructs.
AB  - Cell-sheet techniques have been proven effective in various soft tissue
      engineering applications. In this experiment, we investigated the feasibility of
      bone tissue engineering using a hybrid of mesenchymal stem cell (MSC) sheets and
      PLGA meshes. Porcine MSCs were cultured to a thin layer of cell sheets via
      osteogenic induction. Tube-like long bones were constructed by wrapping the cell
      sheet on to PLGA meshes resulting in constructs which could be cultured in
      spinner flasks, prior to implantation in nude rats. Our results showed that the
      sheets were composed of viable cells and dense matrix with a thickness of about
      80-120 microm, mineral deposition was also observed in the sheet. In vitro
      cultures demonstrated calcified cartilage-like tissue formation and most PLGA
      meshes were absorbed during the 8-week culture period. In vivo experiments
      revealed that dense mineralized tissue was formed in subcutaneous sites and the 8
      week plants shared similar micro-CT characteristics with native bone. The neo
      tissue demonstrated histological markers for both bone and cartilage, indicating
      that the bone formation pathway in constructs was akin to endochondral
      ossification, with the residues of PLGA having an effect on the neo tissue
      organization and formation. These results indicate that cell-sheet approaches in
      combination with custom-shaped scaffolds have potential in producing bone tissue.

PMID- 17553511
TI  - Emulsification in turbulent flow 2. Breakage rate constants.
AB  - Systematic experimental study of the effects of several factors on the breakage
      rate constant, k(BR), during emulsification in turbulent flow is performed. These
      factors are the drop size, interfacial tension, viscosity of the oil phase, and
      rate of energy dissipation in the flow. As starting oil-water premixes we use
      emulsions containing monodisperse oil drops, which have been generated by the
      method of membrane emulsification. By passing these premixes through a narrow-gap
      homogenizer, working in turbulent regime of emulsification, we study the
      evolution of the number concentration of the drops with given diameter, as a
      function of the emulsification time. The experimental data are analyzed by a
      kinetic scheme, which takes into account the generation of drops of a given size
      (as a result of breakage of larger drops) and their disappearance (as a result of
      their own breakage process). The experimental results for k(BR) are compared with
      theoretical expressions from the literature and their modifications. The results
      for all systems could be described reasonably well by an explicit expression,
      which is a product of: (a) the frequency of collisions between drops and
      turbulent eddies of similar size, and (b) the efficiency of drop breakage, which
      depends on the energy required for drop deformation. The drop deformation energy
      contains two contributions, originating from the drop surface extension and from
      the viscous dissipation inside the breaking drop. In the related subsequent
      paper, the size distribution of the daughter drops formed in the process of drop
      breakage is analyzed for the same experimental systems.

PMID- 17553510
TI  - Elution behavior of diaminopimelic acid and related diamino acids using the
      advanced Marfey's method.
AB  - The advanced Marfey's method consists of a chromatography technique for the
      separation of amino acids into each enantiomer by derivatization with 1-fluoro
      2,4-dinitrophenyl-5-L-leucinamide (L-FDLA), and a detection method using liquid
      chromatography/mass spectrometry (LC/MS) which can determine the non-empirically
      the absolute configuration of various amino acids including the non-protein ones.
      However, this method has not been applied to the determination of the absolute
      configuration of an amino acid with a "meso" configuration such as diaminopimelic
      acid (A2pm). In the present study, this method was successfully applied to
      determine the absolute configurations of diaminosuccinic acid (DAS), A2pm,
      cystine (Cys), selenocystine (SeCys) and homocystine (HomoCys) using a
      racemization procedure and the DL-FDLA method, and the resulting elution behavior
      was summarized as follows: (1) the LL- and meso-isomers were eluted prior to the
      DD-isomer except for one case; (2) the LL- and meso-isomers are closely eluted
      and the elution was occasionally reversed; (3) the retention time for both the L-
      and D-derivatives of the meso-isomer was not changed; (4) the complementary use
      of the two solvent systems using CH3CN and MeOH was effective to obtain a
      chromatogram with a high resolution; (5) the abnormality, such as the elution
      order and peak shape, was observed in the elution behavior of DAS.

PMID- 17553512
TI  - Electrochemical techniques for the removal of Reactofix Golden Yellow 3 RFN from
      industrial wastes.
AB  - Electrochemical methods for pollution abatement have been shown to be viable
      alternatives or complementary to biological treatment in some instances,
      especially when pollutants are recalcitrant to biological processing.
      Electrochemical oxidation and reduction have been found successful in decomposing
      the most resilient compounds, and electrolysis is assigned an important role in
      the elucidation of the electrode process. Small well-defined cathodic and anodic
      peak were observed that on controlled-potential electrolysis (CPE) reduced
      substantially with a considerable decrease in color and absorbance. The rate of
      decrease of the current and absorbance was found to exhibit a first-order
      dependence. The COD of the solutions showed a decrease from 1416 to 352 mg/L. No
      peak could be observed in the voltammograms after CPE, indicating the absence of
      any electroactive substance left in the solutions. Results show that
      electrochemical reduction is a superior technology for treatment of dyes, as
      there is no simultaneous addition of anions, such as sulfate or chloride.

PMID- 17553513
TI  - Preparation of monodisperse thermo-sensitive poly(N-isopropylacrylamide) hollow
      microcapsules.
AB  - We successfully developed a novel and simple method for preparation of
      monodisperse thermo-sensitive poly(N-isopropylacrylamide) (PNIPAM) hollow
      microcapsules at the interface of water-in-oil (W/O) single emulsions at a
      temperature below the lower critical solution temperature (LCST) of PNIPAM. The
      prepared PNIPAM microcapsules are featured with hollow structures and thin
      membranes, high monodispersity, excellent reversible thermo-sensitivity and fast
      response to environmental temperature. This approach exhibits great interests in
      preparing monodisperse thermo-sensitive microcapsules for encapsulating bioactive
      materials or drugs requiring mild encapsulation conditions, because of the
      flexibility in choosing substances being dissolved in the aqueous phase. The
      preparation methodology demonstrated in this study provides a unique approach for
      preparing monodisperse hollow polymeric microcapsules with W/O single emulsions.

PMID- 17553514
TI  - Contact angle measurements by confocal microscopy for non-destructive microscale
      surface characterization.
AB  - Contact angle measurements are of great importance in surface characterization
      but the practical use has often been limited to macroscopic dimensions
      (millimeters). Therefore, we have developed a confocal microscopy method that
      allows non-destructive measurements of both low (<30 degrees ) and high (30
      degrees -90 degrees ) contact angles. Low contact angles were measured by
      reconstructing the drop profile from the interference patterns in droplets
      condensed from atmospheric humidity. At higher contact angles water droplets with
      a small amount of fluorescein were sprayed onto the surfaces and 3D-image stacks
      were recorded and used to extract the contact angle. Suitable drop sizes were
      between a few up to about 50 mum radius, using a 40x magnification objective.
      Using drops >10 micrometers radius for microcontact angle measurements a good
      correlation was obtained between measured micro- and macrocontact angles. After
      microcontact angle measurements the surfaces were rinsed and heavy meromyosin
      motor fragments were adsorbed to the surface. Importantly, the sensitive actin
      propelling function of these motor proteins was not affected by the previous
      contact angle measurements using fluorescent droplets. This suggests that the
      methodology should be suitable for non-destructive characterization of different
      parts of micropatterned surfaces being developed for biological assays.

PMID- 17553515
TI  - Chromium removal from water using LTA zeolites: effect of pH.
AB  - The effect of pH changes on the ability of the synthetic zeolite NaA to remove
      Cr(3+) from water by ion exchange was investigated. The exchange rate was
      improved by working near neutrality. Despite of the occurrence of simultaneous
      adsorption, precipitation or cation exchange phenomena, spectroscopic analyses of
      samples taken at different contact times suggested the presence of an unique
      chromium environment in the solid phase. The increase in pH observed during the
      ion exchange favored polymerization-precipitation of chromium species present in
      solution, which, in turn, improved the metal removal capacity of zeolite NaA
      above the values expected for a pure cationic exchange reaction.

PMID- 17553516
TI  - The influence of maternal immunization on infant immune responses.
AB  - The vaccination of human mothers during pregnancy leads to transplacental
      transfer of antibody which can provide protection to the neonate during early
      life. This active transfer is a receptor-mediated event with preferential
      transport of antibody of the IgG1 and IgG3 subclasses via the FcR(n) receptor.
      The efficiency of trans-placental transfer is dependent on a range of factors
      including: placental integrity, the total IgG concentration in maternal blood,
      the type of vaccine, the timing of vaccine administration during gestation, the
      gestational age of the fetus at birth and the IgG subclass involved. The kinetics
      of maternal and infant serological responses has been extensively studied using
      Haemophilus influenzae b (Hib) vaccination as a model.

PMID- 17553517
TI  - DNA vaccination against pseudorabies virus and bovine respiratory syncytial virus
      infections of young animals in the face of maternally derived immunity.
AB  - DNA vaccination represents a unique opportunity to overcome the limitations of
      conventional early life vaccine strategy which is restricted by the effects of
      maternally derived immunity. The pseudorabies virus (PRV) infection model in
      neonatal piglets was employed to demonstrate that a single DNA vaccination was
      able to prime memory humoral immune responses in the face of high concentrations
      of maternally derived antibodies. Immunity induced under these conditions
      protected against challenge with virulent PRV at the end of the fattening period,
      but long-term protective responses were not correlated with the kinetics of the
      initial serological responses. The bovine respiratory syncytial virus (BRSV)
      infection model in young calves was similarly studied, however the ability of DNA
      vaccination to prime memory humoral responses in the face of high concentrations
      of maternally derived antibodies was not confirmed, illustrating that the
      performance of DNA vaccination varies between species and/or infectious disease
      targets. However, in the BRSV model system it was evident that DNA vaccination
      could prime cell-mediated immunity in the face of high concentrations of
      maternally derived antibodies. Although not sufficient to ensure protection
      against clinical disease or viral excretion as a standalone vaccination strategy,
      priming by DNA vaccination was proven to establish cell-mediated immune responses
      for subsequent recall with an inactivated vaccine booster. Under these
      conditions, protection against challenge virus re-excretion was correlated with
      interferon (IFN) gamma-producing T-cell responses. The safety and the efficacy of
      DNA vaccine priming in very young animals in the face of high concentrations of
      maternally derived antibody provides a unique opportunity to design innovative
      and flexible vaccination programs to ensure uninterrupted protection under field
      conditions.

PMID- 17553518
TI  - Identifying highly mutated IGHD genes in the junctions of rearranged human
      immunoglobulin heavy chain genes.
AB  - The reliable identification of IGHD genes within human immunoglobulin heavy
      chains is challenging with up to one third of rearrangements having no
      identifiable IGHD gene. The short, mutated IGHD genes are generally assumed to be
      indistinguishable from the N-REGIONS of non-template encoded nucleotides that
      surround them. In this study we have characterised N-REGIONS, demonstrating the
      importance of nucleotide composition biases in the addition process, including
      the formation of homopolymer tracts. We then use a simulation approach to
      determine the likelihood of misidentification of highly mutated IGHD genes among
      the JUNCTION nucleotides. These likelihoods provide general rules for the
      identification of mutated D-REGIONs, and suggest that longer D-REGIONs (>25
      nucleotides) with as many as ten mutations can be identified with a low risk of
      error. Shorter D-REGIONs (>16 nucleotides) with as many as four mutations are
      also identifiable. The reliability of different alignments is dependent upon the
      junction length (combined N-REGIONs and D-REGION). Data is presented that can
      guide the alignment of sequences with junction lengths from 5 to 50 nucleotides,
      including explicit selection between two D-REGION possibilities. The use of such
      a statistically-based approach to the alignment of IGHD genes will improve the
      reliability of the partitioning of immunoglobulin sequences, and this in turn
      will facilitate the study of the many processes that contribute to the diversity
      of the immunoglobulin repertoire.

PMID- 17553519
TI  - A novel automated method for enumeration of Chlamydia trachomatis inclusion
      forming units.
AB  - Chlamydia trachomatis is an obligate intracellular pathogen that primarily
      infects epithelial cells. Traditional methods for quantification of inclusion
      forming units (IFUs) rely upon infection of epithelial cell monolayers in vitro.
      Following incubation for approximately 2 days, inclusion bodies that result from
      infection of cells are detected by immunofluorescent staining with an antibody
      conjugated to a fluorescent dye. These inclusion bodies are then manually counted
      by microscopic examination of multiple, randomly selected fields of view. This
      requires substantial operator time and is subject to investigator bias. We have
      developed a novel method in which we utilize an automated microplate ImmunoSpot
      reader to count C. trachomatis IFUs. Following infection of epithelial cells in a
      96-well plate and subsequent incubation, IFUs are fixed and detected with an anti
      C. trachomatis LPS monoclonal antibody. Immobilized antibody is detected with a
      biotinylated secondary antibody and visualized enzymatically with streptavidin
      alkaline phosphatase and the colorimetric substrate nitro-blue tetrazolium
      chloride/5-bromo-4-chloro-3-indolyl-phospate (NBT/BCIP). IFUs are then enumerated
      with the ImmunoSpot system. This method has been used to quantify IFUs from all
      cell lines traditionally used for chlamydial propagation, including L929, McCoy,
      HeLa and HaK cells. IFU numbers obtained are comparable to those determined by
      traditional microscopic counting. In addition, the method can be applied to rapid
      determination of serum-neutralizing titers for vaccine studies, and we have also
      applied this approach to quantify Chlamydia recovered from vaginal swabs
      collected from infected animals. This method provides for rapid enumeration of
      IFU counts while minimizing investigator bias and has potential applications for
      both research and diagnostic use.

PMID- 17553521
TI  - Effects of photoperiod and temperature on the rate of larval development, food
      conversion efficiency, and imaginal diapause in Leptinotarsa decemlineata.
AB  - Larvae of Leptinotarsa decemlineata developed faster and consumed less food under
      short-day (Sd, 12:12 h light:darkness) than under long-day (Ld, 18:6 h L:D)
      conditions. The average index of food conversion efficiency was 5.4 in the Ld (25
      degrees C), and 7.2 and 11.9 (at 20 and 25 degrees C, respectively) in the Sd
      insects. Pupae were smaller under the Ld conditions due to a greater loss of
      biomass during the prepupal period that was nearly twice longer than in the Sd
      insects. Virgin Ld females laid eggs for 6 months and survived 13 months. The
      lack of oviposition, reduced food intake, and behavioural changes characterised
      diapause in the Sd adults. Application of 100 microg JH III to newly ecdysed
      adults was used to probe diapause intensity. At 25 degrees C, the treatment
      elicited oviposition most effectively in females that were just transferred from
      the Ld to the Sd conditions. A distinctly lower response occurred in insects that
      had been kept under Sd conditions since hatching; their transfer to Ld conditions
      at the time of treatment had little effect on JH sensitivity. JH application to
      Sd females reared at 20 degrees C caused enlargement of the germaria but no eggs
      were formed.

PMID- 17553520
TI  - Production of monoclonal antibodies that recognize the extracellular domain of
      mouse langerin/CD207.
AB  - Langerin CD207 is a type II transmembrane protein. It is responsible for the
      formation of Birbeck granules, which are intracellular organelles within
      Langerhans cells, the dendritic cells of stratified squamous epithelia like the
      epidermis. Because current anti-CD207 antibodies have limitations, we prepared
      new monoclonals by immunizing rats with the extracellular region of mouse
      Langerin followed by a boost with enriched Langerhans cells (LCs). We secured a
      large panel of mAbs, most of which reacted with the carboxy terminal carbohydrate
      recognition domain. These mAbs could be used to immunoblot and immunoprecipitate
      mouse Langerin and to stain the cell surface and intracellular pools of CD207 by
      FACS analysis. Labeling of Birbeck granules was also achieved by immunoelectron
      microscopy. Anti-CD207 identified LCs in the epidermis and skin draining lymph
      nodes of BALB/c and C57BL/6 mice, but BALB/c mice had an additional Langerin(+)
      population in spleen, thymus and mesenteric lymph node. This additional subset
      had higher levels of CD8 and CD205 than epidermal LCs, and also had a less mature
      phenotype, i.e., lower MHC II, CD40 and CD86. Subcutaneous injection of IgG but
      not IgM forms of these new anti-CD207 mAbs led to rapid and selective labeling of
      the Langerin(+) cells in skin draining lymph nodes as well as spleen. The new IgG
      anti-CD207 mAbs should be useful for further research on LCs and dendritic cells
      including an evaluation of the consequences of antigen delivery within anti-CD207
      mAbs in vivo.

PMID- 17553522
TI  - Design and isolation of temperature-sensitive mutants of Gal4 in yeast and
      Drosophila.
AB  - Little is known about mechanisms responsible for the temperature-sensitive (ts)
      phenotype, or of the transferability of ts mutants of a specific gene between
      organisms. Using a structure-based approach, nine ts mutants of Gal4 were
      generated in yeast by mutating four DNA binding residues. Two of these nine yeast
      ts mutants were cloned into P element vectors under control of the Elav and GMR
      promoters and transgenic Drosophila lines were generated. These were crossed to
      UAS reporter lines and progeny were characterized for reporter gene expression as
      a function of temperature. Both of these yeast ts mutants show a ts phenotype in
      Drosophila and result in rapid induction of reporter gene expression upon
      shifting to the permissive temperature. Exposed, functional residues involved in
      protein-ligand or protein-protein interactions appear to be attractive candidate
      sites for generating ts mutants that are transferable between organisms.

PMID- 17553523
TI  - Crystal structure of Medicago truncatula UGT85H2--insights into the structural
      basis of a multifunctional (iso)flavonoid glycosyltransferase.
AB  - (Iso)flavonoids are a diverse group of plant secondary metabolites with important
      effects on plant, animal and human health. They exist in various glycosidic
      forms. Glycosylation, which may determine their bioactivities and functions, is
      controlled by specific plant uridine diphosphate glycosyltransferases (UGTs). We
      describe a new multifunctional (iso)flavonoid glycosyltransferase, UGT85H2, from
      the model legume Medicago truncatula with activity towards a number of
      phenylpropanoid-derived natural products including the flavonol kaempferol, the
      isoflavone biochanin A, and the chalcone isoliquiritigenin. The crystal structure
      of UGT85H2 has been determined at 2.1 A resolution, and reveals distinct
      structural features that are different from those of other UGTs and related to
      the enzyme's functions and substrate specificities. Structural and comparative
      analyses revealed the putative binding sites for the donor and acceptor
      substrates that are located in a large cleft formed between the two domains of
      the enzyme, and indicated that Trp360 may undergo a conformational change after
      sugar donor binding to the enzyme. UGT85H2 has higher specificity for flavonol
      than for isoflavone. Further substrate docking combined with enzyme activity
      assay and kinetic analysis provided structural insights into this substrate
      specificity and preference.

PMID- 17553524
TI  - The crystal structure of the human (S100A8/S100A9)2 heterotetramer, calprotectin,
      illustrates how conformational changes of interacting alpha-helices can determine
      specific association of two EF-hand proteins.
AB  - The EF-hand proteins S100A8 and S100A9 are important calcium signalling proteins
      that are involved in wound healing and provide clinically relevant markers of
      inflammatory processes, such as rheumatoid arthritis and inflammatory bowel
      disease. Both can form homodimers via distinct modes of association, probably of
      lesser stability in the case of S100A9, whereas in the presence of calcium S100A8
      and S100A9 associate to calprotectin, the physiologically active heterooligomer.
      Here we describe the crystal structure of the (S100A8/S100A9)(2) heterotetramer
      at 1.8 A resolution. Its quaternary structure illustrates how specific
      heteroassociation is energetically driven by a more extensive burial of solvent
      accessible surface areas in both proteins, most pronounced for S100A9, thus
      leading to a dimer of heterodimers. A major contribution to tetramer association
      is made by the canonical calcium binding loops in the C-terminal halves of the
      two proteins. The mode of heterodimerisation in calprotectin more closely
      resembles the subunit association previously observed in the S100A8 homodimer and
      provides trans stabilisation for S100A9, which manifests itself in a
      significantly elongated C-terminal alpha-helix in the latter. As a consequence,
      two different putative zinc binding sites emerge at the S100A8/S100A9 subunit
      interface. One of these corresponds to a high affinity arrangement of three His
      residues and one Asp side-chain, which is unique to the heterotetramer. This
      structural feature explains the well known Zn(2+) binding activity of
      calprotectin, whose overexpression can cause strong dysregulation of zinc
      homeostasis with severe clinical symptoms.

PMID- 17553525
TI  - The use of intraventricular thrombolytics in intraventricular hemorrhage.
AB  - Intraventricular hemorrhage (IVH) is associated with a high mortality and
      morbidity. Patients with this disorder may now be offered the possibility of
      treatment. This treatment comes in the form of intraventricular thrombolytics. At
      present a large randomized trial is testing the efficacy of intraventricular rt
      PA in IVH in the setting of intracranial hemorrhage (ICH) . Preliminary data
      suggests that it may be successful in patients with IVH in this setting. This
      trial is the accumulation of animal and human trials completed over the last 20
      years.

PMID- 17553526
TI  - Incidence of dementia and associated risk factors in Japan: The Osaki-Tajiri
      Project.
AB  - The incidence of dementia and risk factors has not been fully investigated in
      Japan. Following a prevalence study in 1998, we investigated the incidence and
      associated factors in the same population in 2003 and 2005. Randomly selected 771
      residents in Tajiri were targeted. The final participants included 204 (65.2%)
      healthy older adults (Clinical Dementia Rating, CDR 0) and 335 (73.1%) people
      with questionable dementia (CDR 0.5). We analyzed the incidence of dementia and
      dementing diseases, and possible risk factors. The risk factors included
      demographics, lifestyle-related factors, vascular risk factors, cognitive
      functions, and MRI findings. Overall, 3.9% of the CDR 0 and 37.0% of the CDR 0.5
      participants developed dementia during the 5-year period, whereas 40.2% of the
      CDR 0.5 participants developed dementia during the 7-year period. Older adults
      had a higher incidence. Higher CDR Box scores had a higher incidence. Of the
      dementing diseases, 60.8% of participants developed Alzheimer' disease (AD),
      followed by vascular dementia (VaD), 17.9%. Logistic regression analyses showed
      that age, MMSE, cognitive functions such as recent memory, and generalized
      atrophy were significant predictors of progression to AD. Similarly, predictive
      factors for progression to VaD were age, MMSE, cognitive functions such as
      frontal function, and white matter lesions and cerebrovascular diseases. A
      comprehensive system including CDR, cognitive tests, and MRI, is recommended in
      community-based health policy planning.

PMID- 17553527
TI  - dl-3n-butylphthalide prevents stroke via improvement of cerebral microvessels in
      RHRSP.
AB  - The purpose of the study is to establish a model of cold-induced stroke in
      hypertensive rats, and to study the preventive effect of dl-3n-butylphthalide (
      NBP ) on stroke. Stroke-prone renovascular hypertension(RHRSP) was created in
      Sprague-Dawley rats. The animals were assigned randomly to NBP, aspirin treated
      and vehicle control group, with administration of the medications for 7 days, and
      then subjected to cold treatment in an environmentally controlled chamber for 3
      days to induce the occurrence of stroke. The incidence of stroke, the volume of
      the brain lesion, patency of the microvessels by FITC-dextran perfusion and the
      number of microvessels by immunohisochemical detection of vwF were investigated.
      Cold induced different types of stroke in RHRSP. The incidence of ischemic stroke
      and the volume of the infarct were decreased, and the perfused microvessels were
      increased with NBP pretreatment. Our data suggest that NBP prevents cold-induced
      ischemic stroke via improvement of cerebral microvessels.

PMID- 17553528
TI  - The occurrence of selected antibiotics in Hong Kong coastal waters.

PMID- 17553529
TI  - Assessment of polyaromatic hydrocarbons (PAHs) and polychlorinated biphenyls
      (PCBs) in surface sediments of the Inner Clyde Estuary, UK.

PMID- 17553530
TI  - Hazard assessment of silicone oils (polydimethylsiloxanes, PDMS) used in
      antifouling-/foul-release-products in the marine environment.
AB  - Non-eroding silicone-based coatings can effectively reduce fouling of ship hulls
      and are an alternative to biocidal and heavy metal-based antifoulings. The
      products, whose formulations and make up are closely guarded proprietary
      knowledge, consist of a silicone resin matrix and may contain unbound silicone
      oils (1-10%). If these oils leach out, they can have impacts on marine
      environments: PDMS are persistent, adsorb to suspended particulate matter and may
      settle into sediment. If oil films build up on sediments, infiltration may
      inhibit pore water exchange. PDMS do not bioaccumulate in marine organisms and
      soluble fractions have low toxicity to aquatic and benthic organisms. At higher
      exposures, undissolved silicone oil films or droplets can cause physical-mechanic
      effects with trapping and suffocation of organisms. These 'new' effects are not
      covered by current assessment schemes. PDMS make the case that very low water
      solubility and bioavailability do not necessarily preclude damage to marine
      environments.

PMID- 17553531
TI  - Detection of high concentrations of 137Cs in Walleye pollock collected in the Sea
      of Japan.

PMID- 17553532
TI  - Effects of beach nourishment on sediments and benthic assemblages.
AB  - Beach nourishment (i.e. the addition of sediments transported from other source
      locations) is increasingly used to counteract erosion of coastal areas. We tested
      whether sediment descriptors (grain size structure and organic content) and
      macrobenthic assemblages (species composition and abundance) differed among
      replicated shores previously exposed to nourishment alone (N), nourishment in
      combination with pre-existing hard structures (N+H) or no nourishment (NoN) along
      about 50 km of shores of the Emilia Romagna region (North Adriatic Sea, Italy).
      There was large variation among shores. Two out of three N shores were nearly
      defaunated, while one N shore had species composition and abundances comparable
      to NoN shores. There were also large differences between N and N+H shores, the
      latter possessing higher abundances of organisms and the presence of species that
      do not usually occur in the nearshore surf habitats in this region. More than 50%
      of the variability in the benthic assemblages was related to variations in the
      grain size structure of the sediments among shores. The results suggest that
      beach nourishments may lead to modifications of sedimentary environments and
      inhabiting fauna, but the resulting effects may be strongly related to local
      conditions, which dictate the rate at which added sand is redistributed.

PMID- 17553533
TI  - Atmospheric wet deposition of PAHs to the sea-surface microlayer.
AB  - Sea-surface microlayer (SML) and subsurface seawater samples (SSW) collected from
      Singapore's coastal environment were analyzed for 14 polycyclic aromatic
      hydrocarbons (PAHs) in the dissolved (DP) and suspended particulate phase (SPM).
      Samples were collected prior to and after rainfall events to ascertain the
      contribution of wet atmospheric deposition of PAH enrichment to the SML. The
      concentration ranges of summation operatorPAHs in the SML before rain and after
      wet deposition were 2.6-46.2 ngL(-1) and 4.3-278.0 ngL(-1), respectively, for the
      DP and 3.8-31.4 ngL(-1) and 12.8-1280 ngL(-1), respectively, for the SPM. Load
      factors (i.e. concentration after wet deposition relative to before wet
      deposition) of the atmospheric wet deposition for DP and SPM ranged from 1.4 to
      42.9 and 1.2 to 337, respectively. This study provides the first data on PAH
      concentration, enrichment (i.e. concentration of PAHs in SML relative to
      subsurface water) and load factors in the SML before and after wet deposition to
      the ocean surface.

PMID- 17553535
TI  - Chronic SKF83959 induced less severe dyskinesia and attenuated L-DOPA-induced
      dyskinesia in 6-OHDA-lesioned rat model of Parkinson's disease.
AB  - SKF83959, a recently identified selective agonist of putative phosphoinositide
      linked (PI-linked) D(1) dopamine (DA) receptor, is found to elicit excellent anti
      parkinsonism effects in monkeys and rodents. In the present study, the effects of
      SKF83959 on L-dihydroxyphenylalanine (L-DOPA)-induced dyskinesia (LID) were
      assessed in a unilateral 6-hydroxydopamine (6-OHDA) lesioned rat model of
      Parkinson's disease (PD). The results indicated that chronic L-DOPA (6 mg/kg)
      induced a progressive dyskinesia-like behavior in PD rats, whereas SKF83959 (0.5
      mg/kg) elicited significantly less severe dyskinesia while exerts its anti
      parkinsonian action effectively. Application of D(1) receptor, but not D(2),
      alpha or 5-HT receptor antagonist attenuated SKF83959-induced dyskinesia,
      indicating that a D(1) receptor-mediated events, assumed via PI-linked D(1)
      receptor. Interestingly, chronic co-administration of SKF83959 significantly
      reduced LID at no expanse of reduction in the anti-parkinsonian potency in PD
      rats. However, this anti-dyskinesia effect was not observed while SKF83959 was
      acutely administered in rats with established LID. This implies that chronic
      SKF83959 attenuated the development of dyskinesia. Immediate early gene FosB is
      previously reported to positively associate with dyskinesia. However, we found
      that the anti-dyskinesia effect of chronic SKF83959 was independent of FosB since
      SKF83959 produced stronger FosB expression in the lesioned striatum than that of
      L-DOPA while exerting its anti-dyskinesia action. The present data demonstrated
      that SKF83959 reduces LID by attenuating the development of dyskinesia; the
      underlying signaling pathway for the anti-dyskinesia action of SKF83959 appears
      not to depend on FosB.

PMID- 17553534
TI  - Molecular mechanisms of preeclampsia.
AB  - Preeclampsia is a major cause of maternal, fetal and neonatal mortality
      worldwide. The mechanisms that initiate preeclampsia in humans have been elusive,
      but some parts of the puzzle have begun to come together. A key discovery in the
      field was the realization that its major phenotypes, such as hypertension and
      proteinuria, are due to excess circulating soluble fms-like tyrosine kinase-1
      (sFlt-1, also referred to as sVEGFR-1). sFlt-1 is an endogenous anti-angiogenic
      protein that is made by the placenta and acts by neutralizing the pro-angiogenic
      proteins vascular endothelial growth factor (VEGF) and placental growth factor
      (PlGF). More recently, soluble endoglin, another circulating anti-angiogenic
      protein was found to synergize with sFlt-1 and contribute to the pathogenesis of
      preeclampsia. Abnormalities in these circulating angiogenic proteins are not only
      present during clinical preeclampsia, but also antedate clinical symptoms by
      several weeks. This review will summarize our current understanding of the
      molecular mechanism of preeclampsia, with an emphasis on the recently
      characterized circulating anti-angiogenic proteins.

PMID- 17553536
TI  - Daily physical activity counts vs structured activity counts in lean and
      overweight Dutch children.
AB  - The objectives of this study were to compare daily physical activities, and
      activities performed according to a structured protocol, measured with tri-axial
      accelerometers (Tracmor-4), between lean and overweight children. Fourteen
      overweight children (59.8+/-9.5 kg) and fifteen lean matched controls (47.2+/-8.7
      kg) wore the Tracmor-4 daily, during 12+/-1.3 h, for one week in their home
      environment. Of these, 24 children participated in a sports afternoon, where they
      performed activities according to the same structured protocol. In addition,
      physical activity was estimated using a modified Baecke questionnaire. Body
      composition was determined. Total mean Tracmor counts/day were significantly
      lower for the overweight children than for the lean (overweight: 46.1+/-6.9 vs.
      lean: 54.4+/-11.2 kCounts/day, p=0.02), while reported activities (Baecke score)
      were similar. When performing activities according to the structured protocol,
      there was no difference in mean Tracmor counts between the two groups
      (overweight: 36.3+/-6.9 vs. lean: 34.7+/-6.6 kCounts, p=0.6). Daily physical
      activities were inversely related to percentage body fat (r(2)=0.29, p<0.01);
      structured activities were not. As compared to lean children, overweight children
      moved less without being aware of it; yet exerted the same movements per
      activity. We conclude that in overweight children daily physical activities were
      reduced and structured activities performed according to instructions were not.
      In order to prevent progressive overweight or obesity, overweight children should
      take part in as many as possible structured and scheduled sports activities
      throughout the week, and be encouraged to behave physically active in daily life.

PMID- 17553537
TI  - Body temperature daily rhythm adaptations in African savanna elephants (Loxodonta
      africana).
AB  - The savanna elephant is the largest extant mammal and often inhabits hot and arid
      environments. Due to their large size, it might be expected that elephants have
      particular physiological adaptations, such as adjustments to the rhythms of their
      core body temperature (T(b)) to deal with environmental challenges. This study
      describes for the first time the T(b) daily rhythms in savanna elephants. Our
      results showed that elephants had lower mean T(b) values (36.2 +/- 0.49 degrees
      C) than smaller ungulates inhabiting similar environments but did not have larger
      or smaller amplitudes of T(b) variation (0.40 +/- 0.12 degrees C), as would be
      predicted by their exposure to large fluctuations in ambient temperature or their
      large size. No difference was found between the daily T(b) rhythms measured under
      different conditions of water stress. Peak T(b)'s occurred late in the evening
      (22:10) which is generally later than in other large mammals ranging in similar
      environmental conditions.

PMID- 17553538
TI  - 8-Methyl-4-(3-diethylaminopropylamino) pyrimido [4',5';4,5] thieno (2,3-b)
      quinoline (MDPTQ), a quinoline derivate that causes ROS-mediated apoptosis in
      leukemia cell lines.
AB  - The present study reports the biological activity of 8-methyl-4-(3-diethylamino
      propylamino) pyrimido [4';5';4,5] thieno (2,3-b) quinoline (MDPTQ), a quinoline
      derivative structurally related to ellipticine and suggests a possible mechanism
      through which the compound induces apoptosis in carcinoma cell lines. Out of the
      8 cell lines used in the study as representatives of different types of cancer,
      MDPTQ was found to be effective only against leukemia cell lines (HL-60 and K
      562) whereas it had no effect on normal human bone marrow cells (BMC) which were
      used as controls. Fall mitochondrial membrane potential and increased reactive
      oxygen species (ROS) were mainly responsible for inducing apoptosis in the two
      cell lines. Cell death was demonstrated by increase in caspase 3 activity as well
      as phosphatidyl serine exposure. Pre-incubation with N-acetylcysteine (NAC)
      reduced the increased ROS and caspase 3 activity as well as phosphatidyl serine
      exposure. MDPTQ also caused cell cycle arrest in these cell lines. The above
      study for the first time reports the mode of action of a quinoline derivative,
      which could be a possible future candidate for leukemia therapy. However, there
      are lot of questions that need to be answered in terms of signalling pathways and
      its effects on animal models.

PMID- 17553539
TI  - Resistance of a vaccinia virus A34R deletion mutant to spontaneous rupture of the
      outer membrane of progeny virions on the surface of infected cells.
AB  - The extracellular form of vaccinia virus is referred to as an enveloped virion
      (EV) because it contains an additional lipoprotein membrane surrounding the
      infectious mature virion (MV) that must be discarded prior to cell fusion and
      entry. Most EVs adhere to the surface of the parent cell and mediate spread of
      the infection to adjacent cells. Here we show that some attached EVs have
      ruptured envelopes. Rupture was detected by fluorescence microscopy of unfixed
      and unpermeabilized cells using antibodies to the F13 and L1 proteins, which line
      the inner side of the EV membrane and the outer side of the MV membrane,
      respectively. The presence of ruptured EV membranes was confirmed by immunogold
      transmission electron microscopy. EVs with broken membranes were present on
      several cell lines examined including one deficient in glycosaminoglycans, which
      are thought to play a role in breakage of the EV membrane prior to fusion of the
      MV. No correlation was found between EVs with ruptured membranes and actin tail
      formation. Studies with several mutant viruses indicated that EV membranes
      lacking the A34 protein were unbroken. This result was consistent with other
      properties of A34R deletion mutants including resistance of the EV membrane to
      polyanions, small plaque formation and low infectivity that can be increased by
      disruption of the EV membrane by freezing and thawing.

PMID- 17553540
TI  - Kinetic characterisation of an enriched Nitrospira culture with comparison to
      Nitrobacter.
AB  - Nitrospira and Nitrobacter are nitrite-oxidising bacteria commonly identified in
      nitrogen removal wastewater treatment plants. Little is known about the growth
      parameters of Nitrospira or the effects of environmental conditions or inhibitory
      compounds on Nitrospira activity. These bacterial properties were investigated
      using an enriched Nitrospira culture and an enriched Nitrobacter culture or
      Nitrobacter literature values. Compared to Nitrobacter, Nitrospira was found to
      have a comparable optimal pH range (8.0-8.3); similar normalised activity
      temperature relationship (0.44e(0.055(T-15))) for temperatures between 15 and 30
      degrees C and a similar oxygen half-saturation constant, K(O) (0.54+/-0.14 mgL(
      1)). The major differences identified were that Nitrospira had a lower nitrite
      half-saturation constant, K(S) (0.9+/-0.07 mgNO(2)-NL(-1)); lower inhibition
      threshold concentrations for free ammonia (between 0.04 and 0.08 mg NH(3)-NL(-1))
      and free nitrous acid (less than 0.03 mg HNO(2)-NL(-1)) and a higher yield
      (0.15+/-0.04 g VSS g N(-1)). Therefore, Nitrospira is more likely to dominate
      nitrite oxidation under conditions with low ammonium and nitrite concentrations,
      which would provide an advantage to them due to their lower K(S) value while
      avoiding any free ammonia or free nitrous acid inhibition.

PMID- 17553541
TI  - Distribution characteristics of nonylphenol in Jiaozhou Bay of Qingdao and its
      adjacent rivers.
AB  - Nonylphenol (NP) is an endocrine disruptor and causes harmful effects including
      feminization and carcinogenesis to various organisms. Consequently, its
      contamination in natural waters has received wide concerns. This study aims to
      investigate the seasonal variation and contamination level of nonylphenol in
      Jiaozhou Bay of Qingdao and its adjacent rivers. A total of 10 phenolic compounds
      including alkylphenol, chlorophenol and bisphenol A were measured in water,
      suspended solids and sediments in winter (January), spring (April) and summer
      (July) of 2005. The results showed that nonylphenol accounted for the majority of
      phenolic compounds and that its concentrations in Jiaozhou Bay ranged between
      20.2-269 ng l(-1), 17.1-77.5 ng l(-1) and 3.6-299 ng g(-1)dw in surface water,
      suspended solids and surface sediment, respectively. There existed a significant
      correlation between nonylphenol in water and in suspended solids. The
      concentration of nonylphenol in water varied with seasons and generally showed a
      decreasing order of July>April>January. The concentrations of nonylphenol in the
      adjacent rivers were much higher with the maximum of 28600 ng l(-1) in surface
      water. The spatial distribution of nonylphenol in Jiaozhou Bay was influenced by
      freshwater discharge from the adjacent rivers as well as current circulation
      system within the bay. The pollution level of nonylphenol in Jiaozhou Bay was
      comparable to other highly polluted areas of the world and its possible effects
      on local organisms were discussed.

PMID- 17553542
TI  - Characterization and optimization of long-term controlled release system for
      groundwater remediation: a generalized modeling approach.
AB  - A well-based reactive barrier system using controlled-release KMnO4 has been
      recently developed as a long-term in situ treatment option for plumes of dense
      and non-aqueous phase liquids in groundwater. In order to take advantage of the
      merits of controlled release systems (CRS) in environmental remediation, the
      release behavior needs to be optimized for the hydrologic and environmental
      conditions of target treatment zone. Where release systems are expected to be
      operated over long times, like for the reactive barriers, it may only be
      practical to describe the long-term behavior numerically. We developed a
      numerical model capable of describing release characteristics associated with
      variable forms and structures of long-term CRS. Sensitivity analyses and
      illustrative simulations showed that the release kinetics and durations would be
      constrained by changes in agent solubility, bulk diffusion coefficients, or
      structures of the release devices. The generality of the numerical model was
      demonstrated through simulations for CRS with monolithic and double-layered
      matrices. The generalized model was then used for actual design and analyses of
      an encapsulated-matrix CRS, which can yield constant release kinetics for several
      years. A well-based reactive barrier system (4.05 x 10(3)m3) using the
      encapsulated-matrix CRS can release approximately 1.65 kg of active agent (here
      MnO4(-)) daily over the next 6.6 yr, creating prolonged reaction zone in the
      subsurface. The generalized model-based, target-specific approach using the long
      term CRS could provide practical tool for improving the efficacy of advanced in
      situ remediation schemes such as in situ chemical oxidation, bioremediation, or
      in situ redox manipulation. Development of techniques for adjusting the bulk
      diffusion coefficients of the release matrices and facilitating the lateral
      spreading of the released agent is warranted.

PMID- 17553543
TI  - Occurrence and fate of polycyclic musks in wastewater treatment plants in
      Kentucky and Georgia, USA.
AB  - Wastewater treatment plants (WWTPs) are a potential of source of polycyclic musks
      in the aquatic environment. In this study, contamination profiles and mass flow
      of polycyclic musks, 1,3,4,6,7,8-hexahydro-4,6,6,7,8,8
      hexamethylcyclopenta[gamma]-2-benzopyran (HHCB), 7-acetyl-1,1,3,4,4,6-hexamethyl
      1,2,3,4-tetrahydronaphthalene (AHTN), and HHCB-lactone (oxidation product of
      HHCB), in two WWTPs, one located in Kentucky (Plant A, rural area) and the other
      in Georgia (Plant B, urban), USA, were determined. HHCB, AHTN and HHCB-lactone
      were detected in the influent, effluent, and sludge samples analyzed. The
      concentrations in wastewater samples varied widely, from 10 to 7,030 ng/l, 13 to
      5,400 ng/l, and 66 to 790 ng/l, for HHCB, AHTN, and HHCB-lactone, respectively.
      Sludge samples contained HHCB at <0.02-36 microg/g dry weight, AHTN at <0.02-7.2
      microg/g dry weight, and HHCB-lactone at <0.05-17 microg/g dry weight. Based on
      the daily flow rates and mean concentrations of polycyclic musks, the estimated
      discharge of total polycyclic musks to the rivers was 21 g/day from Plant A and
      31 g/day from Plant B. Mass balance analysis suggested that only 30% of HHCB and
      AHTN entering the plants was accounted for in the effluent and the sludge.
      Removal efficiencies of HHCB and AHTN in the two WWTPs ranged from 72% to 98%. In
      contrast, HHCB-lactone concentrations increased following the treatment.
      Concentrations of polycyclic musks in sludge were on the order of several parts
      per million. Incineration of sludge at one plant reduced the concentration of
      polycyclic musks.

PMID- 17553544
TI  - Biodegradation of nonylphenol polyethoxylates under Fe(III)-reducing conditions.
AB  - Biodegradation behavior of nonylphenol polyethoxylates (NPEOs) under Fe(III)
      reducing conditions was investigated. The study demonstrated that NPEOs could be
      rapidly biodegraded under Fe(III)-reducing conditions. Almost 60% of the total
      NPEOs were removed within three days and the maximum biodegradation rate was
      34.95+/-0.84 microM d(-1). NPEOs were degraded via sequential removal of ether
      units under Fe(III)-reducing conditions. No nonylphenol polyethoxy-carboxylates
      (NPECs) were formed in this process. This ether removal process was coupled to
      Fe(III) reduction. Nonylphenol (NP), nonylphenol monoethoxylate (NP1EO), and
      nonylphenol diethoxylate (NP2EO) slightly accumulated in the anaerobic
      biodegradation process. The accumulation of these estrogenic metabolites led to a
      significant increase in the estrogenic activity during the biodegradation period.
      The calculated estrogenic activity reached its top on day 14 when the total
      concentration of these estrogenic metabolites was maximal. This is the first
      report of the primary biodegradation behavior of NPEOs under Fe(III)-reducing
      conditions. These findings are of major environmental importance in terms of the
      environmental behavior of NPEO contaminants in natural environment.

PMID- 17553545
TI  - Chromatographic retention-activity relationships for prediction of the toxicity
      pH-dependence of phenols.
AB  - An investigation of the use of the chromatographic retention (log k) as an in
      vitro approach for modeling the pH-dependence of the toxicity to Guppy of phenols
      is developed. A data set of 19 phenols with available experimental toxicity-pH
      data was used. The importance of the mechanism of toxic action (MOA) of phenols
      was studied. log k data at three pH values were used for the phenols
      classification and two groups or 'MODEs' were identified. For one 'MODE' a
      quantitative retention-activity relationship (QRAR) model was calculated.
      Finally, the model was used to assess the toxicity to Guppy of phenols at
      different pH values. The results of this investigation suggest that
      chromatographic retention data allows fish toxicity modeling, in the 5.5-8 pH
      range of interest.

PMID- 17553546
TI  - Electrocatalytic oxidation of methyl tert-butyl ether (MTBE) in aqueous solution
      at a nickel electrode.
AB  - This study utilized the electrocatalytic characteristics of nickel electrode to
      perform degradation of methyl tert-butyl ether (MTBE) in aqueous solution. Lab
      experiments were conducted in a spiltless bath type cell equipped with a nickel
      electrode as working electrode, a platinum wire as counter electrode, and an
      Ag/AgCl electrode as reference electrode. Effects of controlled potential,
      supporting electrolyte, and solution pH on the efficiency of MTBE removal were
      examined under the control of the constant-potential conditions. Experiment
      results showed that the optimum electrolytic condition was operated at 0.35 V in
      a 1M KOH electrolyte solution, and the initial 20 mgl(-1) MTBE was reduced by 73%
      within 180 min under the optimum control. As using 1M Na2SO4 and 1M KCl as
      electrolyte, the efficiency of MTBE removal dropped to 60% and 50% under the
      similar controls. Comparing with various pH controls, the strong basic condition
      is favorable for electrocatalytic oxidation of MTBE in the Ni-electrolytic
      system. The efficiency of MTBE removal showed a rising trend with increasing
      initial pH of the solution. The formation of a redox NiOOH/Ni(OH)2 layer on the
      anode surface, which was observed on the SEM image, can explain that nickel plays
      a mediator role on improving electrocatalytic oxidation of MTBE at 0.35 V in a
      strong basic condition. The by-products of MTBE degradation were identified as
      acetone and CO(2) by GC/MS, and the distributions of carbon atoms in acetone,
      CO2, and MTBE were found 22%, 51%, and 27% through the optimum control of
      electrochemical oxidation.

PMID- 17553547
TI  - Electrochemical and FTIR studies of the mutual influence of lead(II) or iron(III)
      and phenol on their adsorption from aqueous acid solution by modified activated
      carbons.
AB  - Cyclic voltammetry and spectral FTIR studies of the influence of activated carbon
      surface modification on the co-adsorption of metal cation (lead or iron) and
      phenol from aqueous acidic solution were carried out. The diversity in surface
      chemical structure was achieved by applying different procedures of inorganic
      matter removal and by modifying the carbon samples in various ways: heating under
      vacuum, aminoxidation in an ammonia-oxygen atmosphere, oxidation with
      concentrated nitric acid. The quantities of adsorbed metal ions (Pb(2+) or
      Fe(3+)) and phenol from solutions containing cation or phenol separately or in a
      mixture were determined. The adsorption capacity from acidic aqueous acidic
      solution depends on the chemical properties of the activated carbon surface
      (e.g., decrease in phenol adsorption with relative lower basicity of the
      adsorbent). The electrochemical parameters of electrodes made from the carbon
      samples were estimated, and some possible electrochemical reactions were
      determined from voltammograms recorded in acid electrolyte solution containing
      adsorbed species (separately or as a mixture). Relationships were found between
      metal ion adsorption and electrochemical behavior of Pb(2+)/Pb(4+) and
      Fe(3+)/Fe(2+) couples on the one hand, and the presence of phenol in the
      solutions tested and the influence of surface chemistry of the carbon electrodes
      on electrochemical processes on the other. The changes in adsorption capacity
      with respect to the adsorbates used and the changes in FTIR spectra of the
      carbons as a result of adsorption and/or coupling phenol molecules are discussed.

PMID- 17553548
TI  - Sex differences noted in mercury bioaccumulation in Magicicada cassini.
AB  - This study focuses on quantitative differences in mercury bioaccumulation based
      on the sex of the specimen. The species of interest is an herbivorous,
      terrestrial insect. Male and female periodical cicadas (genus: Magicicada)
      analyzed using combustion atomic absorption spectrophotometry exhibit different
      levels of mercury bioaccumulation. The concentration of mercury in Magicicada
      cassini males was significantly higher than the concentration in females of the
      same species.

PMID- 17553549
TI  - Disruption of thyroid hormone binding to sea bream recombinant transthyretin by
      ioxinyl and polybrominated diphenyl ethers.
AB  - A number of chemicals released into the environment share structural similarity
      to the thyroid hormones (THs), thyroxine (T(4)) and triiodothyronine (T(3)) and
      it is thought that they may interfere with the thyroid axis and behave as
      endocrine disruptors (EDs). One of the ways by which such environmental
      contaminants may disrupt the TH axis is by binding to TH transporter proteins.
      Transthyretin (TTR) is one of the thyroid hormone binding proteins responsible
      for TH transport in the blood. TTR forms a stable tetramer that binds both T(4)
      and T(3) and in fish it is principally synthesized in the liver but is also
      produced by the brain and intestine. In the present study, we investigate the
      ability of some chemicals arising from pharmaceutical, industrial or agricultural
      production and classified as EDs, to compete with [I(125)]-T(3) for sea bream
      recombinant TTR (sbrTTR). Ioxinyl, a common herbicide and several polybrominated
      diphenyl ethers were strong inhibitors of [I(125)]-T(3) binding to TTR and some
      showed even greater affinity than the natural ligand T(3). The TTR competitive
      binding assay developed offers a quick and effective tool for preliminary risk
      assessment of chemicals which may disrupt the thyroid axis in teleost fish
      inhabiting vulnerable aquatic environments.

PMID- 17553550
TI  - Airborne silica levels in an urban area.
AB  - In order to evaluate the exposure levels of the general population we studied the
      concentrations of silica particles in the inhalable particulate fraction (PM10)
      in different meteorological-climate periods in an urban area of Rome. In order to
      determine the concentration and the granulometric spectrum of silica particles,
      PM10 sampled by a cascade impactor was analysed by X-ray diffractometry (XRD) and
      by scanning electron microscopy equipped with a thin-window system for X-ray
      microanalysis (SEM/EDX). Over the period September 2004-October 2005 the
      abundance of silica particles as evaluated by SEM/EDX ranged from 1.6 to 10.4% of
      the total PM10 particulate, with a weight concentration of free crystalline
      silica, evaluated by XRD, in the range 0.25-2.87 microg/m3. The mean diameter of
      silica particles ranged from 0.3 to 10.5 microm, with more than 87% of particles
      having a diameter of less than 2.5 microm. The correlations between SEM/EDX and
      XRD data seem to suggest that the airborne silica particles in the urban location
      studied were mainly in the form crystalline silica. A strong relationship was
      found between the meteorological-climate conditions and the concentration level
      of free crystalline silica. This result suggests that the Southern winds from the
      Sahara desert carry an important amount of silica particles into Mediterranean
      Europe.

PMID- 17553551
TI  - And, more on: assessing aspirin responsiveness using the verify now aspirin
      assay.

PMID- 17553552
TI  - Screening for aspirin resistance in stable coronary artery patients by three
      different tests.
AB  - BACKGROUND: Aspirin (ASA) failure to inhibit in vitro platelet function had been
      termed ASA resistance. The prevalence of this phenomenon as measured with
      different platelet function tests varies widely among studies. OBJECTIVES: In
      this study, we propose to determine the prevalence of ASA non-responsiveness in
      stable coronary artery patients using three different tests. PATIENTS AND
      METHODS: One hundred ninety-one patients with a stable coronary artery disease
      and receiving secondary ASA prophylaxis (250 mg/day) were tested. For each
      patient the ASA-induced platelet inhibition was determined using three different
      tests: Ivy Bleeding time (BT), collagen/epinephrine closure time (CEPI-CT; PFA
      100, Dade-Behring) and urinary 11-dehydrothromboxane B2 (uTxB2) excretion level.
      The agreement between these tests was evaluated by kappa statistics test.
      RESULTS: The prevalence of biological ASA resistance was 15.7% (n=30), 20.4%
      (n=39) and 24.6% (n=47) by BT, PFA-100 and UTxB2, respectively. Only fourteen
      patients (7.3%) were non-responders for two tests: 6 (3.1%) BT/ PFA-100; 1 (0.5%)
      BT/UTxB2; 7 (3.7%) PFA-100/UTxB2). A poor agreement was found between these three
      methods and only 3 patients were resistant with all the tests (1.6%). CONCLUSION:
      The lack of agreement supposed that different types of aspirin resistance exist.
      Thus, combination of two tests or more could be a primary solution for a better
      identification of ASA resistant patients. This hypothesis must be confirmed by a
      large-scale randomized study with clinically well-defined endpoints.

PMID- 17553553
TI  - Re: lymphatic mapping and sentinel node biopsy in women with high-risk
      endometrial cancer.

PMID- 17553554
TI  - Surgicopathologic outcome of laparoscopic versus open radical hysterectomy.
AB  - OBJECTIVE: To compare the surgicopathologic outcome of total laparoscopic radical
      hysterectomy (LRH) with that of abdominal radical hysterectomy (ARH) for the
      treatment of early-stage cervical cancer. METHODS: Radical hysterectomy specimens
      of sequential patients undergoing LRH (N=50) were compared with those of
      historical controls selected from consecutive women who have had conventional ARH
      (N=48), and who met the same criteria for eligibility as the cases. To evaluate
      the extent of parametrial resection, parametrial tissues were systematically
      measured at their widest dimensions before tissue processing. RESULTS: No
      difference was found in demographics, histologic type, tumor stage and grade
      between the two groups. The parametrial width was similar between LRH and ARH in
      both type II (right parametrium: 2.4 cm (1-3) vs. 2.3 (1.8-4.0), p=0.28; left
      parametrium: 2.3 cm (1.8-4) vs. 2.2 (1.2-3.0), p=0.54) and type III radical
      hysterectomy (right parametrium: 3.8 cm (2.3-6.5) vs. 3.4 (1.7-7.0), p=0.59; left
      parametrium: 3.6 cm (2-6) vs. 3.5 (1.5-6.5), p=0.82). There were no significant
      differences between the two groups with regard to lymph nodes yield and
      likelihood of identifying positive margins or metastatic disease. CONCLUSION: Our
      results suggest that laparoscopically managed patients with cervical cancer
      undergo a similar extent of surgery as those treated with the traditional ARH, as
      judged by objective pathologic criteria.

PMID- 17553555
TI  - Serotonin decreases aggression via 5-HT1A receptors in the fighting fish Betta
      splendens.
AB  - The role of the monoamine neurotransmitter serotonin (5-HT) in the modulation of
      conspecific aggression in the fighting fish (Betta splendens) was investigated
      using pharmacological manipulations. We used a fish's response to its mirror
      image as our index of aggressive behavior. We also investigated the effects of
      some manipulations on monoamine levels in the B. splendens brain. Acute treatment
      with 5-HT and with the 5-HT1A receptor agonist 8-OH-DPAT both decreased
      aggressive behavior; however, treatment with the 5-HT1A receptor antagonist WAY
      100635 did not increase aggression. Chronic treatment with the selective
      serotonin reuptake inhibitor fluoxetine caused no significant changes in
      aggressive behavior and a significant decline in 5-HT and 5-hydroxyindoleacetic
      acid (5-HIAA) concentrations. Treatment with the serotonin synthesis inhibitor p
      chlorophenylalanine resulted in no change in aggression, yet serotonergic
      activity decreased significantly. Finally, a diet supplemented with L-tryptophan
      (Trp), the precursor to 5-HT, showed no consistent effects on aggressive behavior
      or brain monoamine concentrations. These results suggest a complex role for
      serotonin in the expression of aggression in teleost fishes, and that B.
      splendens may be a useful model organism in pharmacological and toxicological
      studies.

PMID- 17553556
TI  - The partial 5-HT(1A) agonist buspirone reduces the expression and development of
      l-DOPA-induced dyskinesia in rats and improves l-DOPA efficacy.
AB  - Dopamine (DA) replacement therapy with l-DOPA remains the standard
      pharmacotherapy for Parkinson's disease (PD). Unfortunately, chronic l-DOPA
      treatment is accompanied by development of motor fluctuations and l-DOPA-induced
      dyskinesia (LID). While serotonin (5-HT)(1A) agonists acutely reduce these
      complications, their prophylactic and long-term effects are not well-delineated.
      To test this, male Sprague-Dawley rats received unilateral 6-hydroxydopamine (6
      OHDA) lesions. In experiment 1, l-DOPA-primed rats were pre-treated with Vehicle
      (0.9% NaCl), various doses of the partial 5-HT(1A) agonist, buspirone (0.25, 1.0
      or 2.5 mg/kg, ip) or buspirone (2.5 mg/kg, ip)+the 5-HT(1A) antagonist, WAY100635
      (0.5 mg/kg, ip) 5 min prior to l-DOPA (12 mg/kg+15 mg/kg benserazide, ip). Rats
      were tested for LID using the abnormal involuntary movements (AIMs) scale and
      motor performance using the forepaw adjusting steps test (FAS). In experiment 2,
      l-DOPA-naive rats received co-administration of l-DOPA+buspirone (1.0 or 2.5
      mg/kg, ip) for 2 weeks. AIMs and FAS were measured throughout. In l-DOPA-primed
      rats, buspirone dose-dependently reduced LID and improved l-DOPA-related motor
      performance due to action at the 5-HT(1A) receptor. In l-DOPA-naive rats,
      buspirone delayed LID development while improving l-DOPA's anti-parkinsonian
      efficacy indicating the potential long-term benefits of 5-HT(1A) agonists for
      reduction of l-DOPA-related side effects.

PMID- 17553557
TI  - Sample-based assessment of the microbial etiology of bovine necrotic
      vulvovaginitis.
AB  - A semiquantitative evaluation of potential bacterial pathogens was correlated to
      the severity of lesions during an outbreak of bovine necrotic vulvovaginitis
      (BNVV) on an Israeli dairy herd. Bacteriologic examination of 287 vaginal swabs
      from 104 post-calving heifers showed a highly significant correlation between
      Porphyromonas levii colony forming unit numbers and the clinical scores of the
      lesions, when assessed by an ordinal regression statistical model. No such
      correlation was found for the other bacteria included in the study. Nineteen
      samples taken for virological examinations resulted negative for bovine herpes
      viruses 1, 2, 4 and 5. Thus the results of this study substantiate the essential
      role of P. levii in the etiology of BNVV and indicate that BHV4 is not required
      as a predisposing factor to the syndrome.

PMID- 17553558
TI  - Does successful attainment of developmental tasks lead to happiness and success
      in later developmental tasks? A test of Havighurst's (1948) theses.
AB  - This study tested Havighurst's (1948) contention that successful attainment of
      age-specific developmental tasks leads to happiness and success in achieving
      subsequent tasks. A longitudinal study on 146 participants was carried out to
      investigate the links between developmental progression in adolescence and young
      adulthood and happiness, which was assessed by two indices: high self-esteem and
      low symptomatology. The importance individuals place on achieving normative
      developmental tasks and current developmental status was assessed six times
      during adolescence and young adulthood, self-esteem and symptomatology were
      assessed five times. Results revealed a shift in the time frames for
      accomplishing the stage-specific developmental tasks. Findings with respect to
      the interrelatedness and progressive attainment partially supported Havighurst's
      contentions. Although remarkable concurrent links between the two indices of
      happiness and developmental status were found, developmental outcomes were not
      predictive for later happiness.

PMID- 17553559
TI  - Transition behavior in fatigue of human dentin: structure and anisotropy.
AB  - The influence of tubule orientation on the transition from fatigue to fatigue
      crack growth in human dentin was examined. Compact tension (CT) and rectangular
      beam specimens were prepared from the coronal dentin of molars with three unique
      tubule orientations (i.e., 0 degrees , 45 degrees and 90 degrees). The CT
      specimens (N=25) were used to characterize fatigue crack initiation and steady
      state cyclic extension, whereas the rectangular beams (N=132) were subjected to 4
      pt flexure and used in quantifying the stress-life fatigue response. The
      transition behavior was analyzed using both the Kitagawa-Takahashi and El Haddad
      approaches. Results showed that both the fatigue crack growth and stress-life
      responses were dependent on the tubule orientation. The average Paris Law
      exponent for crack growth perpendicular (90 degrees) to the tubules (m=13.3+/
      1.1) was significantly greater (p<0.05) than that for crack growth oblique (45
      degrees) to the tubules (m=11.5+/-1.87). Similarly, the fatigue strength of
      dentin with 90 degrees tubule orientation was significantly lower (p<0.05) than
      that for the other two orientations, regardless of the range of cyclic stress.
      The apparent endurance strengths of specimens with 0 degrees (44MPa) and 45
      degrees (53MPa) orientations were nearly twice that of the 90 degrees (24MPa)
      orientation. Based on these results, human dentin exhibits the largest degree of
      anisotropy within the stress-life regime and the transition from fatigue to
      fatigue crack growth occurs under the lowest cyclic stress range when the tubules
      are aligned with the cyclic normal stress (90 degrees orientation).

PMID- 17553560
TI  - The binding of HIV-1 gp41 membrane proximal domain to its mucosal receptor,
      galactosyl ceramide, is structure-dependent.
AB  - The peptide of HIV-1 envelope gp41 (a.a 628-683), referred to herein as P5,
      contains P1, a conserved galactose-specific lectin domain for binding the mucosal
      HIV-1-receptor, galactosyl ceramide (GalCer), as shown earlier, and a potential
      calcium-binding site (a.a 628-648). P1 contains contiguous epitopes recognized by
      the broadly neutralizing antibodies 2F5, 4E10, Z13. However, similar neutralizing
      antibodies could not be raised in animal model using immunogens based on these
      epitopes. We now show that the structure of both P5 and P1 peptides, as measured
      by circular dichroism, differs according to their environment: aqueous or
      lipidic, and as a function of calcium concentration. P5, but not P1, binds to
      calcium with a low binding affinity constant in the order of 2.5x10(4). Calcium
      binding results in a conformational change of P5, leading in turn to a decrease
      in affinity for GalCer. Hence, the affinity of the gp41-lectin site for the
      galactose harbored by the mucosal HIV-1 receptor GalCer is modulated by the
      peptide secondary and tertiary structure and the local environment. Therefore,
      definition of the conformation of this novel extended gp41 membrane proximal
      region, containing the conserved peptide P1 and the Ca(2+) binding site, could
      help designing an immunogen efficient at inducing neutralizing anti-HIV-1
      antibodies.

PMID- 17553561
TI  - Vasopressin immunoreactivity, but not vasoactive intestinal polypeptide,
      correlates with expression of circadian rhythmicity in the suprachiasmatic
      nucleus of voles.
AB  - In common voles (Microtus arvalis), natural variation in locomotor behavior can
      be exploited to study the mechanism of pacemaker control over circadian timing of
      behavior. Here we studied daily patterns in numbers of neuropeptide
      immunoreactive suprachiasmatic nucleus neurons in rhythmic, weakly rhythmic, and
      non-rhythmic voles. Circadian rhythmic voles showed circadian variation in
      numbers of vasoactive intestinal polypeptide and vasopressin immunoreactive
      suprachiasmatic nucleus neurons with a peak at zeitgeber time 0. In contrast,
      voles with weak or no circadian rhythmicity exhibited similar fluctuations for
      vasoactive intestinal polypeptide, but a continuous, non-rhythmic high profile
      for vasopressin. Vole suprachiasmatic nucleus neurons do not produce somatostatin
      or substance P. We conclude that the vasopressin system in the common vole
      suprachiasmatic nucleus acts as a principal correlate with expression of
      circadian behavior, in contrast to vasoactive intestinal polypeptide,
      somatostatin, and substance P. We also conclude that high levels of vasopressin
      immunoreactivity in the non-rhythmic vole suprachiasmatic nucleus is in line with
      previously demonstrated hampered release, probably resulting in vasopressin
      accumulation in the suprachiasmatic nucleus. Vasopressin could be a candidate in
      mediating output of the vole circadian clock, leading to circadian expression of
      locomotor behavior.

PMID- 17553562
TI  - Identification and real-time imaging of a myc-expressing neutrophil population
      involved in inflammation and mycobacterial granuloma formation in zebrafish.
AB  - By enhancer trap screening we identified a transgenic zebrafish line showing
      leukocyte-specific YFP expression during late embryo and early larval
      development. Its enhancer detection insertion was mapped near a novel member of
      the myc proto-oncogene family, encoding transcription factors known to be
      important for regulating human myelopoiesis. Characterization of the zebrafish
      myc family showed that only this particular myc gene is strongly expressed in
      leukocytes. To identify the myc/YFP-expressing cell type, we re-examined
      specificity of described myeloid markers by multiplex fluorescent in situ
      hybridization, showing that lcp1 can be considered as a general leukocyte marker,
      csf1r as a macrophage-specific marker, and mpx and lyz as neutrophil-specific
      markers. Subsequent colocalization analysis defined the YFP-positive cells as a
      subset of the neutrophil population. Using real-time confocal imaging we
      demonstrate that these cells migrate to sites of inflammation and are involved in
      innate immune responses towards infections, including Mycobacterium marinum
      induced granuloma formation.

PMID- 17553563
TI  - Disruption of a toxin gene by introduction of a foreign gene into the chromosome
      of Clostridium perfringens using targetron-induced mutagenesis.
AB  - Clostridium perfringens (C. perfringens) has been developed as a potential oral
      delivery vehicle to deliver antigens or therapeutic compounds to Gut-Associated
      Lymphoid Tissue (GALT). However, this recombinant C. perfringens carries a
      plasmid-encoded expression system, which raises several safety concerns regarding
      possible horizontal plasmid transfer and spread of plasmid-associated antibiotic
      resistant genes. Furthermore, this bacterium produces the extracellular theta
      toxin, which poses a potential safety issue for general administration. Using a
      Clostridium-specific-targetron donor plasmid, we inserted the Simian
      Immunodefiency Virus (SIV) p27 gene into the theta toxin gene (pfoA) on the C.
      perfringens chromosome, which simultaneously inactivated the theta gene and
      introduced SIV p27 gene onto the bacterial chromosome. Such mutant C. perfringens
      without an input plasmid or antibiotic resistant gene stably produced a large
      amount of SIV p27 protein during sporulation and did not produce theta toxin.
      Upon oral feeding of the mutant bacteria to mice, intact p27 protein was detected
      in the lower GI tract. The re-engineered C. perfringens provides a biosafe
      efficient oral vehicle to deliver antigen to the gastrointestinal tract.

PMID- 17553564
TI  - A biological and geochemical integrated approach to assess the environmental
      quality of a coastal lagoon (Ravenna, Italy).
AB  - The assessment of the environmental quality of coastal lagoons is rather
      difficult as their intrinsic high variability limits the power of analytical
      chemistry and ecotoxicological approaches. Aim of the present work was to
      integrate geochemical and biological data which were simultaneously collected
      from the Pialassa Baiona lagoon (Ravenna, Italy), and evaluate the usefulness of
      a biomonitoring strategy based on sentinel organisms and biomarkers. Geochemical
      analysis on suspended, surface, and subsurface sediments were performed at five
      different sites of the lagoon; moreover the heavy metal bioaccumulation and a
      battery of biomarkers was evaluated in Mytilus galloprovincialis transplanted in
      the same sites. Heavy metals appeared to be diffused throughout the lagoon
      reaching higher levels in the southernmost sites, and mainly concentrated in
      suspended sediments. Lysosome membrane stability, neutral lipid and lipofuscin
      accumulation, and metallothionein levels in mussels indicated the development of
      a stress syndrome in animals exposed to the polluted sites.

PMID- 17553565
TI  - Molecular genetic analysis of Hungarian patients with the hyper-immunoglobulin M
      syndrome.
AB  - We have identified 9 disease-causing mutations in 18 hyper-immunoglobulin M
      (HIGM) syndrome patients from ten unrelated Hungarian families. CD40L mutation
      resulted in X-linked combined immunodeficiency in 11 patients (6 families) and
      AICDA mutation caused autosomal recessive HIGM characterized by B cell
      immunodeficiency in 5 patients (3 families). Two brothers with a genetically
      undefined form of HIGM and clinical manifestations of B cell deficiency were also
      included in this study. B cells from these two patients had defective CSR and
      skewed pattern of somatic hypermutation. Altogether, a novel CD40L truncation
      mutation (c.470 delA) and a new missense AICDA mutation (p.E58K) were identified.
      Carrier status was defined in 13 clinically healthy individuals allowing prenatal
      genetic testing that was performed in two affected families. This is the first
      comprehensive overview of molecular genetic features of Hungarian patients with
      HIGM syndrome.

PMID- 17553566
TI  - Characterizing the wave aberration in eyes with keratoconus or penetrating
      keratoplasty using a high-dynamic range wavefront sensor.
AB  - PURPOSE: The purpose of this study was to characterize aberrations in 2
      populations of eyes, namely those with keratoconus (KC) and those having
      undergone penetrating keratoplasty (PK), using a large-dynamic range Shack
      Hartmann wavefront sensor. DESIGN: Prospective comparative case series.
      PARTICIPANTS: Twenty-one people with ocular pathologic features (either KC or PK)
      were recruited for this study. A previously compiled population of 190 people
      with no pathologic features other than refractive error was used as a means for
      comparison. METHODS: Thirty-three abnormal eyes (19 with KC and 14 PK) were
      measured using a high-dynamic range wavefront sensor, and Zernike coefficients
      were computed over a 6-mm pupil. The data then were used to characterize the
      populations by themselves, as well as to compare them with the population of
      normal eyes. MAIN OUTCOME MEASURES: Root mean square (RMS) higher-order
      aberration (HOA), percent of higher-order or total aberration variance, and
      magnitude of individual Zernike modes (in micrometers). Visual benefit of
      correcting higher-order aberrations was used when comparing pathologic and normal
      populations. RESULTS: The keratoconic eyes exhibited 2.24 microm of HOA RMS on
      average. Vertical coma accounted for 53+/-32% (mean+/-standard deviation [SD]) of
      the HOA variance and was the most dominant higher-order aberration. The PK
      subjects had an average higher-order RMS of 2.25 microm, and trefoil dominated in
      this population with an average HOA variance contribution of 38+/-23% (mean+/
      SD). The KC and PK higher-order aberrations represented 16+/-20% and 16+/-13%
      (mean+/-SD) of the total aberration variance, whereas the ratio was only 1+/-1%
      in the normal population. A visual benefit calculation on 15 KC eyes and 14 PK
      eyes yielded a result of 4.4+/-2.0 and 6.0+/-1.5 (mean+/-SD), respectively,
      whereas the normal population had a visual benefit of only 2.1+/-0.4.
      CONCLUSIONS: Eyes with KC and PK have higher-order aberrations that are
      approximately 5.5 times more than what is typical in normal eyes. Vertical coma
      is the dominant higher-order aberration in people with KC, whereas PK eyes are
      dominated by trefoil, spherical aberration, and coma. Correcting these
      aberrations may provide substantial improvements in vision beyond what is
      possible with conventional correction methods.

PMID- 17553567
TI  - Replacement of non-heme Fe(II) with Cu(II) in the alpha-ketoglutarate dependent
      DNA repair enzyme AlkB: spectroscopic characterization of the active site.
AB  - The bacterial DNA repair enzyme AlkB is an alpha-ketoglutarate (alphaKG)
      dependent non-heme Fe(II) containing dioxygenase. Here we describe, for the first
      time, the preparation of a Cu(II)-reconstituted form of AlkB in various
      complexes. Spectroscopic characterization showed correct AlkB folding upon
      incorporation of Cu(II) in the active site. The Cu site was classified as a type
      2 site by EPR spectroscopy. The accessibility of the active site metal was
      studied using imidazole as a probe. Although addition of imidazole did not change
      the EPR spectrum of the AlkB-Cu-alphaKG complex, the spectrum of the AlkB-Cu
      succinate complex clearly changed, indicating binding of imidazole at the Cu
      site. Binding of substrate (methylated DNA) to the AlkB-Cu-alphaKG complex did
      not induce changes in the EPR spectrum, demonstrating that the substrate does not
      bind in the immediate vicinity of the metal centre. This work provides a basis
      for advanced EPR approaches aimed at studying the interactions and dynamics of
      AlkB complexes in solution.

PMID- 17553568
TI  - Microglia repetitively isolated from in vitro mixed glial cultures retain their
      initial phenotype.
AB  - In vitro culture of rodent microglia is a common system used to model
      proinflammatory changes in the brain. However, typical postnatal brain isolation
      protocols are time consuming and cell numbers acquired are often a rate-limiting
      factor for experimental progress. Large studies that rely on the use of primary
      microglia can, therefore, require excessive numbers of animals at considerable
      expense, additional technical support and culture incubator space. Although the
      addition of mitogens such as macrophage colony-stimulating factor, granulocyte
      macrophage-colony stimulating factor, and epidermal growth factor to the cultures
      can facilitate a higher yield, this adds additional expense and likely alters the
      microglial phenotype. We have defined a simple, inexpensive modification of our
      standard culture protocol that allows us to repetitively isolate microglia. In
      order to define a method for improving microglia yield, we utilized our standard
      mixed glial culture preparation derived from postnatal day 1-3 mouse brains.
      After isolating microglia from mixed cultures at 14 days in vitro, we added fresh
      media to the cultures for an additional 7 and 14 days to monitor microglial
      proliferation. We acquired a constant number of cells at each successive time
      point although the numbers were reduced from the first isolation. More
      importantly, in order to determine if our successive microglia isolates differed
      phenotypically we characterized several parameters of function. We compared their
      ability to secrete the proinflammatory cytokines interleukin-6 and tumor necrosis
      factor alpha after LPS stimulation. We also contrasted the phagocytic ability,
      morphology, and specific immunoreactivity (CD11b, CD68, CD45 and MHC II) of the
      culture ages. Our data demonstrate that microglia can be obtained from extended
      time cultures provided periodic isolation is performed. Moreover, the cells
      retain a comparable in vitro phenotype. This demonstrates that cells from all
      ages can be combined for any given study. These findings are a viable and
      inexpensive way to increase and extend the microglial yield without increasing
      the number of animals used or adding costly mitogens. This method will be
      particularly useful for the preparation of microglia cultures from limited
      transgenic colonies.

PMID- 17553569
TI  - Quantification of the rat spinal microglial response to peripheral nerve injury
      as revealed by immunohistochemical image analysis and flow cytometry.
AB  - Microgliosis is implicated in the pathophysiology of several neurological
      disorders, including neuropathic pain. Consequently, perturbation of microgliosis
      is a mechanistic and drug development target in neuropathic pain, which
      highlights the requirement for specific, sensitive and reproducible methods of
      microgliosis measurement. In this study, we used the spinal microgliosis
      associated with L5 spinal nerve transection and minocycline-induced attenuation
      thereof to: (1) evaluate novel software based semi-quantitative image analysis
      paradigms for the assessment of immunohistochemical images. Microgliosis was
      revealed by immunoreactivity to OX42. Several image analysis paradigms were
      assessed and compared to a previously validated subjective categorical rating
      scale. This comparison revealed that grey scale measurement of the proportion of
      a defined area of spinal cord occupied by OX42 immunoreactive cells is a robust
      image analysis paradigm. (2) Develop and validate a flow cytometric approach for
      quantification of spinal microgliosis. The flow cytometric technique reliably
      quantified microgliosis in spinal cord cell suspensions, using OX42 and ED9
      immunoreactivity to identify microglia. The results suggest that image analysis
      of immunohistochemical revelation of microgliosis reliably detects the spinal
      microgliosis in response to peripheral nerve injury and pharmacological
      attenuation thereof. In addition, flow cytometry provides an alternative approach
      for quantitative analysis of spinal microgliosis elicited by nerve injury.

PMID- 17553570
TI  - Plasma and serum brain-derived neurotrophic factor (BDNF) in depressed patients
      during 1 year of antidepressant treatments.
AB  - BACKGROUND: Brain-derived neurotrophic factor (BDNF) has been hypothesized to be
      involved in the neurobiology of major depression. The aim of this study was to
      assess the possible relationships between depressive symptoms and serum and/or
      plasma BDNF levels during 1 year of antidepressant treatment. METHODS: Plasma and
      serum BDNF levels were assayed in 15 drug-free depressed patients and in 15
      healthy control subjects at baseline and the 1st, 3rd, 6th and 12th month of
      antidepressant treatment. RESULTS: At baseline, patients' serum and plasma BDNF
      levels were significantly lower (p<.001 and p=.004, respectively) than those
      found in healthy control subjects. However, while from the 1st month of treatment
      patients' plasma BDNF levels did not differ significantly from those observed in
      healthy control subjects, serum BDNF levels in patients remained significantly
      lower at all times. LIMITATIONS: The main limitations of the current study are
      represented by the small sample size and the high discontinuation rate.
      CONCLUSIONS: Untreated depressed patients showed reduced baseline serum and
      plasma BDNF levels, as compared with control subjects. The clinical improvement
      paralleled the normalization of plasma BDNF after 1 month of treatment, while, at
      every assessment time, patients' serum BDNF levels were lower than those of
      control subjects. This would suggest that serum BDNF might represent a non
      specific trait marker of depression.

PMID- 17553571
TI  - Inhibition of Smad7, a negative regulator of TGF-beta signaling, suppresses
      autoimmune encephalomyelitis.
AB  - We studied the role of the Transforming growth factor (TGF)-beta signaling
      antagonist Smad7 in autoimmune central nervous system (CNS) inflammation by using
      specific antisense oligonucleotides (Smad7-as). Elevated Smad7 protein expression
      was found in the spinal cord of SJL/J mice and DA rats with experimental
      autoimmune encephalomyelitis (EAE) and in effector T cells upon antigen
      stimulation. Smad7-as specifically decreased Smad7 mRNA and protein in cell lines
      and in ex-vivo-treated primary mouse lymph node cells (LNC). LNC exposed to Smad7
      as during secondary activation showed reduced proliferation and
      encephalitogenicity. After systemic administration, Smad7-as ameliorated clinical
      signs of active and adoptively transferred EAE, diminished CNS inflammation, and
      reduced Smad7 protein levels in the brain. Smad7-as was found to be incorporated
      by peritoneal macrophages as well as by cells of the liver, kidneys, and
      peripheral lymph nodes. Importantly, Smad7-as treatment was not toxic and did not
      increase extracellular matrix formation. Smad7 inhibition thus represents a novel
      systemic treatment strategy for autoimmune CNS inflammation, targeting TGF-beta
      signaling without TGF-beta-associated toxicity.

PMID- 17553572
TI  - GJB2 (connexin 26) gene mutations in Moroccan patients with autosomal recessive
      non-syndromic hearing loss and carrier frequency of the common GJB2-35delG
      mutation.
AB  - OBJECTIVE: Mutations in the connexin 26 gene (GJB2), which encodes a gap-junction
      protein expressed in the inner ear, have been shown to be responsible for a major
      part of autosomal recessive non-syndromic hearing loss in Caucasians. The aim of
      our study was to determine the prevalence and spectrum of GJB2 mutations,
      including the (GJB6-D13S1830) deletion, in Moroccan patients and estimate the
      carrier frequency of the 35delG mutation in the general population. METHODS:
      Genomic DNA was isolated from 81 unrelated Moroccan familial cases with moderate
      to profound autosomal recessive non-syndromic hearing loss and 113 Moroccan
      control individuals. Molecular studies were performed using PCR-Mediated Site
      Directed Mutagenesis assay, PCR and direct sequencing to screen for GJB2, 35delG
      and del(GJB6-D13S1830) mutations. RESULTS: GJB2 mutations were found in 43.20% of
      the deaf patients. Among these patients 35.80% were 35delG/35delG homozygous,
      2.47% were 35delG/wt heterozygous, 3.70% were V37I/wt heterozygous, and 1 patient
      was E47X/35delG compound heterozygous. None of the patients with one or no GJB2
      mutation displayed the common (GJB6-D13S1830) deletion. We found also that the
      carrier frequency of GJB2-35delG in the normal Moroccan population is 2.65%.
      CONCLUSIONS: These findings indicate that the GJB2-35delG mutation is the major
      cause of autosomal recessive non-syndromic hearing loss in Moroccan population.
      Two other mutations were also detected (V37I and E47X), in agreement with similar
      studies in other populations showing heterogeneity in the frequencies and types
      of mutation in connexin 26 gene.

PMID- 17553573
TI  - Identification of HIV-1 infected infants and young children using real-time RT
      PCR and dried blood spots from Uganda and Cameroon.
AB  - Serodiagnosis of HIV infection in infants born to HIV-infected mothers is
      problematic due to the prolonged presence of maternal antibodies in infants.
      Nucleic acid-based amplification assays have been used to overcome this problem.
      Here a simplified, one-tube, real-time, duplex reverse transcription PCR (RT PCR)
      assay is shown to detect HIV-1 total nucleic acid (TNA) isolated from dried blood
      spots. The detection of TNA, as opposed to DNA alone, increases the HIV target
      molecules and thus makes the assay more robust. This method was used to detect
      HIV from the DBS collected from HIV-1 exposed infants and young children in
      Uganda (n=128) and Cameroon (n=315). The gold-standards used were a plasma viral
      assay in Uganda and Amplicor DNA assay in Cameroon. The concordance of this real
      time assay and the gold standards was 99.2% (127/128) and 99.4% (313/315) with
      the Ugandan and Cameroonian samples, respectively. This simple and cost-effective
      assay is potentially useful for the diagnosis of pediatric HIV infection and for
      evaluating programs to reduce mother-to-child transmission of HIV-1.

PMID- 17553574
TI  - Effects of prenatal infection on prepulse inhibition in the rat depend on the
      nature of the infectious agent and the stage of pregnancy.
AB  - Maternal infection during pregnancy is a risk factor for some psychiatric
      illnesses of neurodevelopmental origin such as schizophrenia and autism. In
      experimental animals, behavioral and neuropathological outcomes relevant to
      schizophrenia have been observed in offspring of infected dams. However, the type
      of infectious agent used and gestational age at time of administration have
      varied. The objective of the present study was to compare the effects of prenatal
      challenge with different immune agents given at different time windows during
      gestation on behavioral outcomes in offspring. For this, pregnant rats were
      administered bacterial endotoxin (lipopolysaccharide, LPS), the viral mimic
      polyinosinic: polycytidylic acid (poly I:C), or turpentine, an inducer of local
      inflammation, at doses known to produce fever, at three different stages in
      pregnancy: embryonic day (E)10-11, E15-16 and E18-19. Prepulse inhibition of
      acoustic startle (PPI) was later measured in male adult offspring. PPI was
      significantly decreased in offspring after prenatal LPS treatment at E15-16 and
      E18-19. Intramuscular injection of pregnant dams with turpentine at E15-16 also
      decreased PPI in adult offspring. Maternal poly I:C administration had no
      significant effect on PPI in offspring. In contrast to prenatal LPS exposure,
      acute LPS administration to naive adult males had no effect on PPI. Thus,
      prenatal exposure both to a systemic immunogen and to local inflammation at brief
      periods during later pregnancy produced lasting deficits in PPI in rat offspring.
      These findings support the idea that maternal infection during critical windows
      of pregnancy could contribute to sensorimotor gating deficits in schizophrenia.

PMID- 17553575
TI  - Population growth study of the rotifer Brachionus sp. fed with triazine-exposed
      microalgae.
AB  - Few data exist on potential toxic effects that pollutants may have on zooplankton
      fed microalgae exposed to pesticides. For that reason, microalgal cultures were
      exposed to different concentrations of the triazine herbicide terbutryn, and used
      as exclusive food source to Brachionus sp. females, with the aim to evaluate
      potential deleterious effects upon population growth, survival, reproduction and
      feeding of the rotifer. Chlorella vulgaris cells were able to accumulate
      terbutryn, removing more than 90% of the total amount of herbicide in all the
      exposed cultures. Growth curves of Brachionus sp. showed that population density
      decreased as terbutryn concentration increased in the microalgal cells. In fact,
      this species of rotifer did not survive beyond four days when fed with microalgae
      exposed to 500 nM terbutryn. Percentage of reproductive females in rotifer
      populations fed with terbutryn-exposed microalgae decreased significantly as
      herbicide concentration increased. In control cultures, reproductive females laid
      a maximum of three eggs per individual; whereas in 100 nM cultures, reproductive
      females laid only one egg per individual throughout the treatment period.
      Terbutryn accumulated in C. vulgaris provoked a decrease in the feeding rate of
      Brachionus sp. cultures fed with these microalgae with respect to control
      cultures. After this treatment period, all the rotifer populations, except those
      fed with 500 nM terbutryn-exposed microalgae, showed recovery patterns when they
      were returned to fresh medium containing herbicide-free microalga. Taking into
      account the results obtained, uptake of pesticides by phytoplankton can directly
      affect higher trophic levels.

PMID- 17553576
TI  - Identification of protein complexes in detergent-resistant membranes of
      Plasmodium falciparum schizonts.
AB  - Merozoite surface proteins of the human malaria parasite Plasmodium falciparum
      are involved in initial contact with target erythrocytes, a process that begins a
      cascade of events required for successful invasion of these cells. In order to
      identify complexes that may play a role in invasion we purified detergent
      resistant membranes (DRMs), known to be enriched in merozoite surface proteins,
      and used blue native-polyacrylamide gel electrophoresis (BN-PAGE) to isolate high
      molecular weight complexes for identification by mass spectrometry. Sixty-two
      proteins were detected and these mostly belonged to expected DRM proteins classes
      including GPI-anchored, multi-membrane spanning and rhoptry proteins. Proteins
      from seven known complexes were identified including MSP-1/7, the low (RAP1/2 and
      RAP1/3), and high (RhopH1/H2/H3) molecular weight rhoptry complexes, and the
      invasion motor complex (GAP45/GAP50/myosinA). Remarkably, a large proportion of
      identified spectra were derived from only 4 proteins: the GPI-anchored proteins
      MSP-1 and Pf92, the putative GPI-anchored protein Pf113 and RAP-1, the core
      component of the two RAP complexes. Each of these proteins predominated in high
      molecular weight species suggesting their aggregation in much larger complexes
      than anticipated. To demonstrate that the procedure had isolated novel complexes
      we focussed on MSP-1, which predominated as a distinct species at approximately
      500 kDa by BN-PAGE, approximately twice its expected size. Chemical cross-linking
      supports the existence of a stable MSP-1 oligomer of approximately 500 kDa,
      probably comprising a highly stable homodimeric species. Our observations also
      suggests that oligomerization of MSP-1 is likely to occur outside the C-terminal
      epidermal growth factor (EGF)-like domains. Confirmation of MSP-1
      oligomerization, together with the isolation of a number of known complexes by BN
      PAGE, makes it highly likely that novel interactions occur amongst members of
      this proteome.

PMID- 17553577
TI  - Cloning and characterization of cathepsin L-like peptidases of Echinococcus
      multilocularis metacestodes.
AB  - Cysteine peptidases have potent activities in the pathogenesis of various
      parasitic infections. Two cDNA clones encoding cysteine peptidases were isolated
      from Echinococcus multilocularis metacestode (EmCLP1 and EmCLP2). EmCLP1 and
      EmCLP2 shared high similarity to the cathepsin L-like peptidases. Immunoblot
      analyses demonstrated that native EmCLP1 and EmCLP2 were present in
      excretory/secretory products and extracts of E. multilocularis metacestodes. By
      immunohistochemistry, native EmCLP1 and EmCLP2 were shown to localize to the
      germinal layer, the brood capsule and the protoscolex. Recombinant EmCLP1 and
      EmCLP2 expressed in Saccharomyces cerevisiae exhibited substrate specificity
      against synthetic peptidyl substrates, Z-Leu-Arg-MCA and Z-Phe-Arg-MCA.
      Furthermore, recombinant enzymes degraded IgG, albumin, type I and IV collagens,
      and fibronectin, which suggested those key roles in parasite-host interactions.
      This is the first report of cysteine peptidases from E. multilocularis, and would
      contribute to control E. multilocularis infections by chemotherapeutic drugs
      and/or immunoprophylaxis.

PMID- 17553578
TI  - Probing the mechanism of FET3 repression by Izh2p overexpression.
AB  - We previously reported a role for the IZH2 gene product in metal ion metabolism.
      Subsequently, Izh2p was also identified as a member of the PAQR family of
      receptors and, more specifically, as the receptor for the plant protein osmotin.
      In this report, we investigate the effect of Izh2p on iron homeostasis. We show
      that overproduction of Izh2p prevents the iron-dependent induction of the Fet3p
      component of the high-affinity iron-uptake system and is deleterious for growth
      in iron-limited medium. We demonstrate that the effect of Izh2p requires cAMP
      dependent kinase and AMP-dependent kinase and is not mediated by general
      inhibition of the Aft1p iron-responsive transcriptional activator. We also show
      that Izh2p-overproduction negatively regulates Nrg1p/Nrg2p- and Msn2p/Msn4p
      dependent reporters. Furthermore, we show that the Nrg1p/Nrg2p and Msn2p/Msn4p
      pairs are epistatic to each other with respect to their effects on FET3
      expression. Finally, we show that the mechanism by which PAQR receptors activate
      signal transduction pathways is likely to be conserved from yeast to humans.

PMID- 17553579
TI  - Reduced expression of the NADPH oxidase NOX4 is a hallmark of adipocyte
      differentiation.
AB  - Adipocyte differentiation is a complex process regulated among other factors by
      insulin and the production of reactive oxygen species (ROS). NOX4 is a ROS
      generating NADPH oxidase enzyme mediating insulin's action in 3T3L1 adipocytes.
      In the present paper we show that NOX4 is expressed at high levels both in white
      and brown preadipocytes and that differentiation into adipocytes results in a
      decrease in their NOX4 mRNA content. These in vitro results were confirmed in
      vivo by demonstrating that in intact adipose tissue the majority of NOX4
      expressing cells are localized within the preadipocyte containing
      stromal/vascular fraction, rather than in the portion consisting of mature
      adipocytes. In line with these observations, quantification of NOX4 mRNA in fat
      derived from different rodent models of insulin resistance indicated that
      alteration in NOX4 expression reflects changes in the ratio of
      adipocyte/interstitial fractions. In conclusion, we reveal that decreased NOX4
      mRNA content is a hallmark of adipocyte differentiation and that NOX4 expression
      measured in whole adipose tissue is not an unequivocal indicator of intact or
      impaired insulin action.

PMID- 17553580
TI  - A rare case of atrial myxoma with biatrial extension.

PMID- 17553581
TI  - Development of a statistically robust quantification method for microorganisms in
      mixtures using oligonucleotide microarrays.
AB  - High-density oligonucleotide arrays can be extremely useful for identifying and
      quantifying specific targets (i.e., ribosomal RNA of microorganisms) in mixtures.
      However, current array identification schemes are severely compromised by
      nonspecific hybridization, resulting in numerous false-positive and false
      negative calls, they lack an adequate internal control for assessing the quality
      of identification, and are dependent on amplification of specific target
      sequences which introduce biases. We have developed a novel approach for the
      routine quantification and identification of metabolically active microorganisms
      in mixed samples. The advantage of our approach over conventional ones is that it
      avoids designing, optimizing, validating, and selecting oligonucleotide probes
      for arrays; also, nonspecific hybridization is no longer a problem. The basic
      principle of the approach is that a fluorescence pattern of a mixed sample is a
      superposition of the fluorescent patterns for each target. The superposition can
      be quantitatively deconvoluted in terms of concentrations of each microbe. We
      demonstrated the utility of our approach by extracting rRNA from three
      microorganisms, making test mixtures, labeling the rRNA, and hybridizing each
      test mixture to DNA oligonucleotide (20-mers, n=346,608) arrays. Comparison of
      known concentrations of individual targets in mixtures to those estimated by the
      solution revealed highly consistent results. The goodness-of-fit of the solution
      revealed that about 90% of the variability in the data could be explained. A new
      analytical approach for microbial identification and quantification has been
      presented in this report. Our findings demonstrate that including signal
      intensity values from all duplexes on the array, which are essentially
      nonspecific to the target organisms, significantly improved predictions of known
      microbial targets. To our knowledge, this is the first study to report this
      phenomenon. In addition, we demonstrate that the method is a self-sufficient
      analytical procedure since it provides statistical confidence of the
      quantification.

PMID- 17553582
TI  - Relationship between baroreceptor cardiac reflex sensitivity and pain experience
      in normotensive individuals.
AB  - In the present study, the relationship between cardiac baroreceptor function and
      the perception of acute pain was investigated in 60 normotensive subjects.
      Baroreceptor reflex sensitivity was determined using the sequence method based on
      continuous blood pressure recordings. A cold pressor test was used for pain
      induction. Visual analogue scales and a questionnaire were applied in order to
      quantify sensory and affective pain experience. Moderated multiple regression
      analysis revealed an inverse relationship between baroreceptor reflex sensitivity
      assessed during painful stimulation and the intensity of experienced pain. This
      relationship was moderated by resting blood pressure, with decreasing blood
      pressure being accompanied by a decrease in the magnitude of the association.
      Furthermore, resting blood pressure was inversely related to pain intensity. The
      inverse association between baroreceptor reflex sensitivity and pain experience
      is discussed as reflecting the well-established pain-inhibiting effect of
      baroreceptor activity. The finding that this relationship was less pronounced in
      the case of lower blood pressure suggests that baroreceptor-mediated pain
      attenuation is reduced in this population.

PMID- 17553583
TI  - Suppressed anger, evaluative threat, and cardiovascular reactivity: a tripartite
      profile approach.
AB  - Despite decades of theory and research implicating suppressed anger in the
      development of cardiovascular disorders involving cardiovascular reactivity
      (CVR), to date the theoretical components of low anger expression, guilt feelings
      over agonistic reactions, and defensive strivings to avoid social disapproval
      have not been used conjointly to profile suppressed anger for the prediction of
      CVR. The purpose of this study, then, was to cluster analyze measures of anger
      expression, hostility guilt, and social defensiveness to create a suppressed
      anger profile (low anger expression, high hostility guilt, high social
      defensiveness) and a non-suppressed profile from a sample of college males.
      Social evaluative threat may be a potent stressor for people who defensively
      suppress anger expression. Thus, to examine the combined effects of suppressed
      anger and social evaluative threat, participants, prior to telling a story to a
      Thematic Apperception Card (TAT), were randomly assigned to either a high-threat
      (story will be compared to stories created by the mentally ill) or a low-threat
      condition (story used to study effects of talking on cardiovascular responses).
      Blood pressure (BP) and heart rate (HR) were monitored during a rest period and
      the subsequent TAT card period. As predicted, suppressed anger males in the high
      threat condition showed the highest levels of diastolic BP and HR change from the
      rest period. The suppressed anger group's systolic BP reactivity was independent
      of threat manipulation. Research implications are discussed.

PMID- 17553584
TI  - Inhibition of Salmonella enterica serotype Enteritidis on agar and raw chicken by
      carvacrol vapour.
AB  - Carvacrol is known to inhibit a number of food borne pathogens. The activity of
      carvacrol vapour was evaluated against S. enterica serotype Enteritidis on
      tryptone soya agar and on pieces of raw chicken. On agar, the size of the
      inhibition zone increased with decreasing volume of agar, increasing vapour
      exposure period, increasing temperature, increasing volume of carvacrol used and
      with decreasing bacterial density. Inhibition was equally effective under aerobic
      and anaerobic conditions. On chicken pieces (10 x 10 x 5 mm, UV-sterilized and
      inoculated with approx. 5 x 10(3) cfu) carvacrol vapour significantly reduced
      viable numbers of salmonellae at 4, 20 and 37 degrees C and all viable cells were
      eliminated by a minimum of 3 h at 37 degrees C (p<0.05). A minimum concentration
      of 20% carvacrol v/v in ethanol was required to achieve a significant reduction
      and from 40% v/v no viable cells were recovered (p<0.05). In conclusion,
      carvacrol vapour is effective at inhibiting the growth of S. enterica serotype
      Enteritidis on agar and at inhibiting and eliminating these bacteria on the
      surface of raw chicken.

PMID- 17553585
TI  - Expression and stability of foreign tags inserted into nsp2 of porcine
      reproductive and respiratory syndrome virus (PRRSV).
AB  - The nonstructural protein 2 (nsp2) of porcine reproductive and respiratory
      syndrome virus (PRRSV) is the single largest protein produced during infection.
      The cDNA of the pCMV-129 infectious PRRSV clone was modified for accepting
      foreign tags by first creating unique Mlu I and SgrA I restrictions sites at
      nucleotide (nt) positions 3219 and 3614, respectively, within the C-terminal
      region of nsp2. cDNAs encoding oligo- and polypeptide tags, including FLAG,
      enhanced green fluorescent protein (EGFP) and luciferase were inserted into the
      newly created restriction sites. The results showed that only the EGFP-containing
      genomes were properly expressed and produced virus. EGFP fluorescence, but not
      EGFP immunoreactivity, was lost during passage of recombinant EGFP viruses in
      culture. Sequencing of a fluorescent-negative EGFP virus showed that the EGFP
      remained intact, except for the appearance of arginine to cysteine mutation at
      position 96, which may interfere with chromophore formation or function.

PMID- 17553586
TI  - Characterization of a eukaryotic type serine/threonine kinase in Spodoptera
      litura nucleopolyhedrovirus-I (SpltNPV-I).
AB  - An open reading frame (ORF) of 819nt coding for a predicted protein of 272 amino
      acids was identified in the genome of Spodoptera litura nucleopolyhedrovirus
      (SpltNPV-I). Sequence derived amino acid sequence analysis of this ORF suggested
      it to be a eukaryotic type protein kinase having conserved I-XI subdomains of
      Hanks kinase. In addition to kinase catalytic domains, this hypothetical protein
      had two bromodomains which could play regulatory roles in transcription. The ORF
      was expressed as approximately 31 kDa apoprotein in E. coli and approximately 33
      kDa glycoprotein in Sf9 cells, and was called SpltNPV-I pk1 or pk1. The protein
      was localized in the nuclei of infected cells of the SpltNPV-I permissive cell
      line, NIV-HA-197. The recombinant protein had autophosphorylation and substrate
      phosphorylation activities in presence of Mn(2+) or Mg(2+), and these activities
      were inhibited by staurosporine. Mutation of Lys-50 to Met but not Lys-44 to Gln
      abolished pk1 kinase activity. Kinetics of pk1 showed that the rate of
      phosphorylation of SpltNPV-I pk1>MBP>histone H1, and both MBP and histone H1 had
      the K(m)s of 3muM. Analysis of phosphorylated protein showed the phosphorylation
      of serine and threonine residues, but not tyrosine. All these results suggested
      that identified SpltNPV-I ORF codes for a serine/threonine kinase.

PMID- 17553587
TI  - Pricing behaviour of pharmacies after market deregulation for OTC drugs: the case
      of Germany.
AB  - OBJECTIVE: To examine the price reactions of German pharmacies to changes made to
      OTC drug regulations in 2004. Prior to these changes, regulations guaranteed
      identical prices in all German pharmacies. METHODS: Two years after market
      deregulation, 256 pharmacies were surveyed to determine the retail prices of five
      selected OTC drugs. A probit regression model was used to identify factors that
      increased the likelihood of price changes. In addition, 409 pharmacy consumers
      were interviewed to gather information on their knowledge of the regulatory
      changes and to better explain consumer behaviour. RESULTS: Data was collected on
      a total of 1215 prices. Two years after deregulation, 23.1% of the participating
      pharmacies had modified the price of at least one of the five OTCs included in
      our study. However, in total, only 7.5% of the prices differed from their pre
      deregulation level. The probit model showed that population density and the
      geographic concentration of pharmacies were significantly associated with price
      changes. Interestingly, the association with the geographic concentration of
      pharmacies was negative. The consumer survey revealed that 47.1% of those
      interviewed were aware of the deregulation. CONCLUSIONS: Our findings indicate
      that, two years after deregulation, very few pharmacies had made use of
      individual pricing strategies; price competition between pharmacies in Germany is
      thus taking place only a very small scale.

PMID- 17553588
TI  - Quality improvement designs are related to the degree of organisation of quality
      systems: an empirical study of hospital departments.
AB  - Quality systems can help departments do the right things and do things right, but
      organisation and design need to be considered. The aim was to analyse whether
      quality systems that include certain quality improvement designs differ with
      regard to organisational factors and degrees of organisation. A questionnaire was
      developed and sent to a random sample of 600 hospital departments in Sweden
      (response rate=75%). A k-means cluster analysis was used to group departments
      into three degrees of organisation. Analyses of variance were done to study
      differences in organisational factors and quality improvement designs among the
      clusters. LISREL analyses were done to study the relationships between
      organisational factors and quality improvement designs. The results showed that
      quality systems that included certain quality improvement designs differed with
      regard to the organisational factors available resources, administration,
      culture, cooperation, and goal achievement. The results also showed that
      departments with quality systems of different organisational degrees used
      different quality improvement designs. Some quality improvement designs may
      require a quality system with a high degree of organisation to support a
      successful implementation. The appended questionnaire could be used to plan
      implementations and evaluate their results.

PMID- 17553589
TI  - Stability of lipid excipients in solid lipid nanoparticles.
AB  - The paper is devoted to the investigation of chemical stability of lipids used as
      excipients in the production of Solid Lipid Nanoparticles (SLN). Different lipids
      and amounts of surfactants were considered. Most of the formulations were
      produced using identical binary surfactant mixtures and concentrations to analyze
      the effect of the chemical nature of the lipids on their stability in SLN. In
      some formulations, surfactants were exchanged or their concentration was
      increased to assess the contribution of surfactants on stability of lipids
      particles. Solid Lipid Nanoparticles were characterized by photon correlation
      spectroscopy, laser diffractometry, zeta potential determination and differential
      scanning calorimetry. Potential effects of lipid crystallinity and modifications
      were assessed. A gas chromatography (GC) analysis in combination with a method
      for lipid extraction from aqueous SLN dispersions was used to investigate the
      chemical stability of the lipid excipients forming the particle matrix. All
      formulations were produced by the hot homogenization technique. The production
      process of SLN itself did not affect the chemical stability of lipid excipient
      forming the particle matrix. The formulations where lipids consisted of
      trigylicerides showed a negligible decomposition of the structure during
      incubation at 25 degrees C. Dynasan 118 showed the highest chemical stability
      (loss<4%) within two years.

PMID- 17553590
TI  - Isolated metastasis of lung cancer to the thyroid gland.
AB  - A 67-year-old man with lung cancer developed an isolated metastasis to the
      thyroid gland. The patient had undergone a right upper lobectomy, followed by
      chemotherapy consisting of cisplatin and etoposide based on post-surgical
      diagnosis of small cell lung cancer. Four years later, he had an isolated
      metastasis to the thyroid gland. The patient underwent a metastasectomy and
      adjuvant chemotherapy including cisplatin and irinotecan. The cancer cells in
      resected thyroid tumor had large nuclei and cytoplasm, and expressed the
      neuroendocrine markers, CD56 and chromogranin A. Retrospectively, the primary
      lung cancer consisted of both small cell and large cell cancer, and the latter
      was consistent with the pathological finding of the thyroid tumor. This is the
      first report to document an isolated recurrence of the lung cancer to the
      thyroid.

PMID- 17553591
TI  - Chromosomal aberrations of malignant pleural effusions of lung adenocarcinoma:
      different cytogenetic changes are correlated with genders and smoking habits.
AB  - Chromosomal aberrations of malignant cells from pleural effusions of 31 cases of
      lung adenocarcinoma were analyzed. Pooled CGH results showed frequent
      amplifications on chromosome arms 1p (22.6%), 1q (35.5%), 2q (25.8%), 3q (38.7%),
      4q (41.9%), 5p (41.9%), 5q (51.6%), 6p (19.4%), 6q (25.8%), 7p (41.9%), 7q
      (35.5%), 8q (32.3%), 12q (38.7%), 13q (22.6%), 14q (35.5%), 17q (19.4%), Xp
      (22.6%), and Xq (38.7%). Frequent deletions were found on 1p (19.4%), 3p (16.1%),
      4q (16.1%), 8p (25.8%), 9p (22.6%), 9q (29.0%), 10q (22.6%), 13q (22.6%), 16p
      (19.4%), 16q (22.6%), 17p (29.0%), 18q (16.1%), 19p (41.9%), 19q (32.3%), 20p
      (19.4%) and 22q (29%). These genomic changes were generally found consistent with
      previous reports of CGH analysis of primary tumors of lung adenocarcinoma. Loss
      of 19q and 22q were more frequently found in our studies (32.3% and 29.0%,
      respectively) than studies of primary tumors (less than 7% for both genetic
      changes). Gain of 11p, although not a frequent finding, was relatively more
      common in this (16%) than other studies (range, 2.9-11.8%). Interestingly,
      occurrences of 3p loss and 11p gain were higher in smokers than non-smokers, and
      deletion of 3p and increased copy number of 11p and Xp appeared more often in
      male than female patients. Among 17 male patients, gain of chromosomal 11p was a
      frequent aberration in tumors of smokers, while gain of Xp was more easily found
      in tumors of non-smokers. One candidate gene located within 11p15, lactate
      dehydrogenase C (LDHC), was selected for further study. Three cases with 11p gain
      had amplified FISH signals of LDHC. Also tumors from smokers or male had
      significantly higher transcript level of LDHC than non-smokers or female,
      respectively. The results demonstrate that different cytogenetic changes of
      malignant pleural effusions from lung adenocarcinoma are correlated with genders
      and smoking habits. The role of LDHC in the carcinogenesis of smoking-related
      lung adenocarcinoma, especially in male patients with pleural effusions, deserves
      further investigations.

PMID- 17553592
TI  - Malfunctions within the Cbl interactome uncouple receptor tyrosine kinases from
      destructive transport.
AB  - Proteins of the Cbl family are adaptor molecules and ubiquitin ligases with major
      functions in the regulation, intracellular transport and degradation of receptor
      tyrosine kinases (RTKs). Due to this central role, mutations that cause
      malfunctions of Cbl or their associated proteins - termed the Cbl interactome -
      easily lead to the transformation of affected cells and eventually the
      development of cancer. This review intends to give an overview on the mechanisms
      of Cbl-mediated cell transformation in light of the dysregulated intracellular
      trafficking of RTKs.

PMID- 17553593
TI  - Contact dermatitis of the hands: cross-sectional analyses of North American
      Contact Dermatitis Group Data, 1994-2004.
AB  - BACKGROUND: Hand dermatitis, including irritant and allergic contact dermatitis
      (ACD), is common. OBJECTIVE: To evaluate allergens, relevant irritants, sources
      and occupations associated with hand contact dermatitis using North American
      Contact Dermatitis Group (NACDG) data. METHODS: A cross-sectional analysis of
      22,025 patients patch tested between 1994 and 2004. RESULTS: Hand involvement was
      found in 6953 patients; 959 had ACD as the only diagnosis. In these 959 patients,
      the 12 most frequent relevant allergens were quaternium-15 (16.5%), formaldehyde
      (13.0%), nickel sulfate (12.2%), fragrance mix (11.3%), thiuram mix (10.2%),
      balsam of Peru (9.6%), carba mix (7.8%), neomycin sulfate (7.7%), bacitracin
      (7.4%), methyldibromoglutaronitrile/phenoxyethanol 2.0% (7.4%), cobalt chloride
      (6.5%), and methyldibromoglutaronitrile/phenoxyethanol 2.5% (6.3%). Rubber
      allergens were most commonly associated with occupation. One third of patients
      with hand ACD had identifiable relevant irritants. LIMITATIONS: Cross-sectional
      analyses prevent evaluation of causal associations. CONCLUSION: In NACDG patients
      with hand ACD, the most common allergens included preservatives, metals,
      fragrances, topical antibiotics, and rubber additives.

PMID- 17553594
TI  - Abnormal keratin expression in circumscribed palmar hypokeratosis.
AB  - BACKGROUND: Circumscribed palmar or plantar hypokeratosis (CPH) is a rare skin
      disorder only recently described. OBJECTIVE: To determine the diagnostic features
      and to provide insight into the pathogenesis of CPH, with analysis of two new
      Japanese cases. METHODS: Dermoscopy, immunohistochemistry, electron microscopy,
      polymerase chain reaction amplification for human papillomavirus (HPV) DNA and
      16S microbial rRNA gene profiling were conducted. RESULTS: Dermoscopy showed
      characteristic features using both dry and jelly immersion observation; step-like
      desquamation and a homogeneous erythema with regularly distributed whitish spots.
      Immunohistochemistry revealed strong staining with anti-pankeratin antibody
      (AE1+AE3) and anti-keratin 16 antibody, and decreased expression of keratin 2e.
      EM revealed a breakage of the corneocytes within their cytoplasm, but structures
      for cell attachment were intact. HPV and lesion-specific bacteria were not
      detected. LIMITATIONS: The number of cases analyzed was two. CONCLUSION:
      Hyperproliferative epidermal state along with enhanced corneocyte fragility may
      account for the unique features in CPH.

PMID- 17553595
TI  - A combined mass spectrometric and cDNA sequencing approach to the isolation and
      characterization of novel antimicrobial peptides from the skin secretions of
      Phyllomedusa hypochondrialis azurea.
AB  - Studies conducted on amphibian skin secretions over the past 40 years have
      isolated and identified huge arrays of bioactive peptides, many of which have
      demonstrated potent anti-microbial activity. Such peptides are attracting
      increasing attention due to the growing problem of pathogenic microorganisms
      resistant to conventional antibiotics. The current study utilized a combined
      proteomic/genomic approach to facilitate the high throughput sequencing of five
      novel dermaseptins and four novel phylloseptins from the skin secretions of
      Phyllomedusa hypochondrialis azurea. Peptides were partially identified using Q
      TOF MS/MS fragmentation and de novo sequencing, while a cDNA library was
      constructed from the lyophilized skin secretion. 3'-RACE reactions used primers
      designed for the highly conserved 5'-signal regions of previously deduced
      dermaseptin precursors. cDNA sequenced peptides were attributed to their
      respective fragmentation spectra to confirm the structure of the final processed
      peptides. Such an approach identified post-translational modifications in
      addition to deciphering isobaric amino acids. Several of the peptides were
      purified to homogeneity and displayed potent antimicrobial activity with minimum
      inhibitory concentrations starting at 0.4 microM when tested against and range of
      Gram-positive and Gram-negative bacteria including Escherichia coli,
      Staphylococcus aureus and Micrococcus luteus.

PMID- 17553596
TI  - Hemodynamic effects of chronic urotensin II administration in animals with and
      without aorto-caval fistula.
AB  - Urotensin II (UTII) is a potent vasoactive peptide. Recent studies have
      demonstrated increased expression of both UTII and its receptor (UTR) expression
      in end-stage congestive heart failure (CHF), but it is unclear whether UTII and
      UTR are late stage markers of decompensation, or earlier adaptive responses. The
      purpose of this study was to measure the effects of chronic UTII administration
      in normal and volume overloaded animals. Chronic 4 weeks administration of UTII
      produced decreases in hemodynamic function in animals not subjected to volume
      overload while returning function to control levels in animals with overload.
      Expression levels of calcium regulatory proteins phospholamban (PLN),
      sarcoplasmic reticulum Ca(2+) ATPase (SERCA2), and Na(+)/Ca(2+) exchanger (NCX)
      were measured to determine if administration of UTII resulted in aberrant Ca(2+)
      handling. Changes in protein expression revealed that UTII influenced Ca(2+)
      handling proteins in normal animals although these changes are not seen in the
      volume overload.

PMID- 17553598
TI  - [Beware of i.v. lines].

PMID- 17553599
TI  - [The spliceosome and its interest for lupus therapy].
AB  - INTRODUCTION: The spliceosome, which is a particle containing a molecule of U-RNA
      and proteins that are specific to each U ribonuclear particle (U-snRNP) or common
      to every U-snRNPs, is one of the numerous nuclear targets recognized by the
      antibodies (Abs) and CD4+ T cells from patients with systemic lupus erythematosus
      and lupus mice. EXEGESIS: We recently characterized a peptide from the
      spliceosomal protein U1-70K (sequence 131-151), which is recognized by the Abs
      and CD4+ T cells from lupus mice and patients. This peptide contains a conserved
      RNP1 motif, which is also present in other spliceosomal proteins targeted by the
      Abs from individuals with lupus. We further showed that peptide 131-151
      containing a phosphoserine at position 140 (peptide P140) possessed tolerogenic
      properties in lupus mice and was recognized by the Abs and CD4+ T cells from
      lupus patients. CONCLUSION: Thanks to its RNP1 motif, the peptide P140 might play
      an important role in the initiation and perpetuation steps of the humoral and
      cellular immune response diversification in lupus individuals. Therapeutic and
      particularly immunomodulating properties of P140 peptide are being evaluated in
      humans (a phase III clinical trial will be undertaken in the next weeks).

PMID- 17553597
TI  - The APOE4 genotype alters the response of microglia and macrophages to 17beta
      estradiol.
AB  - The apolipoprotein E4 (APOE4) gene is a well-known risk factor for Alzheimer's
      disease (AD) and other neurological disorders. Post-menopausal women with AD who
      express at least one APOE4 gene have more severe neuropathology and worsened
      cognitive scores than their non-expressing counterparts. Since 17beta-estradiol
      down-regulates inflammation as part of its neuroprotective role, we examined the
      effect of 17beta-estradiol on the response of microglia to immune activation as a
      function of APOE genotype. Our data show that the anti-inflammatory activity of
      17beta-estradiol is significantly reduced in APOE4 targeted replacement mice
      compared to APOE3 mice. A significant interaction between APOE genotype and the
      response to 17beta-estradiol was observed for NO and cytokine production by
      immune activated microglia. The genotype specific effect was not restricted to
      brain macrophages since peritoneal macrophages from APOE4 ovariectomized mice
      also demonstrated a significant difference in 17beta-estradiol responsiveness.
      ERbeta protein levels in APOE4 microglia were higher than APOE3 microglia,
      suggesting a difference in post-translational protein regulation in the presence
      of the APOE4 gene. Overall, our data indicate that the APOE genotype may be a
      critical component in assessing the effectiveness of 17beta-estradiol's action
      and may impact the neuroprotective role of 17beta-estradiol and of hormone
      replacement therapy on brain function when the APOE4 gene is expressed.

PMID- 17553600
TI  - [New insights into monoclonal gammopathy and multiple myeloma].

PMID- 17553601
TI  - Precepting an unsafe student: the role of the faculty.
AB  - According to a recent study, one of the central findings indicated that
      preceptors require significantly more support than they are currently receiving
      from faculty especially when precepting a student who is engaging in unsafe
      practice. In this grounded theory study, 22 preceptors were interviewed. The
      findings reveal some interesting implications not only regarding the staffing of
      preceptorship programs but also the process of preparing faculty as to how to
      provide preceptors with sufficient and appropriate support throughout the
      preceptorship experience.

PMID- 17553602
TI  - Induration at or near injection site: case definition and guidelines for
      collection, analysis, and presentation of immunization safety data.

PMID- 17553603
TI  - Places and health: a qualitative study to explore how older women living alone
      perceive the social and physical dimensions of their neighbourhoods.
AB  - There is growing interest in the impact that neighbourhood environment might have
      on the health of older people. Although the number of older Australian women,
      particularly those living alone, is projected to increase in coming decades,
      their experiences of neighbourhood have not been exclusively examined. The aims
      of this paper are: (1) to explore, from the perspective of these women, the
      social and physical dimensions of neighbourhoods and (2) to investigate variation
      in these accounts according to whether women lived in areas of higher or lower
      socioeconomic status. Twenty women aged between 75 and 93 years, residing in
      metropolitan Adelaide, South Australia (SA), participated in a series of two in
      depth interviews. Women's perceptions of their neighbourhood, and accounts of
      every-day activities in the community were analysed to determine how both social
      and physical aspects of neighbourhood might relate to health and wellbeing.
      Findings suggest that a reciprocal and trusting relationship with neighbours
      underpinned older women's sense of satisfaction with, and feeling of security
      within, the neighbourhood. Other factors such as living in close proximity to
      services and existing social networks were also seen as important. Women's
      stories demonstrated that they were able to draw on both existing social networks
      and neighbours to sustain their independence and social connection within the
      community. Women living in more disadvantaged areas were more conscious of social
      disconnection in their neighbourhoods, and to the way that traffic noise and
      pollution detracted from their neighbourhood environment. These findings indicate
      that, for older women living alone, trusting and reciprocal relationships with
      neighbours are likely to form an important part of their broader social support
      network and should be recognised in relation to the process of maintaining the
      health of older women living in the community.

PMID- 17553604
TI  - Attentional orienting across the sensory modalities.
AB  - This event-related potential study investigated (i) to what extent incongruence
      between attention-directing cue and cued target modality affects attentional
      control processes that bias the system in advance to favor a particular stimulus
      modality and (ii) to what extent top-down attentional control mechanisms are
      generalized for the type of information that is to be attended. To this end, both
      visual and auditory word cues were used to instruct participants to direct
      attention to a specific visual (color) or auditory (pitch) stimulus feature of a
      forthcoming multisensory target stimulus. Effects of cue congruency were observed
      within 200 ms post-cue over frontal scalp regions and related to processes
      involved in shifting attention from the cue modality to the modality of the task
      relevant target feature. Both directing visual attention and directing auditory
      attention were associated with dorsal posterior positivity, followed by sustained
      fronto-central negativity. However, this fronto-central negativity appeared to
      have an earlier onset and was more pronounced when the visual modality was cued.
      Together the present results suggest that the mechanisms involved in deploying
      attention are to some extent determined by the modality (visual, auditory) in
      which attention operates, and in addition, that some of these mechanisms can also
      be affected by cue congruency.

PMID- 17553605
TI  - Prevalence of large cavum septi pellucidi and its relation to the medial temporal
      lobe structures in schizophrenia spectrum.
AB  - Magnetic resonance imaging was used to evaluate the prevalence of the cavum septi
      pellucidi (CSP) in 154 schizophrenia patients, 47 schizotypal disorder patients,
      and 163 healthy controls. We also explored the relation of a large CSP (> or =6
      mm) with medial temporal lobe structures. No significant difference was found in
      the prevalence of the CSP (76.0% of the schizophrenia patients, 81.6% of the
      controls, and 85.1% of the schizotypal patients) or the large CSP (6.5% of the
      schizophrenia patients, 7.4% of the controls, and 10.6% of the schizotypal
      patients) among the groups, but patients with a large CSP (10 schizophrenia and 5
      schizotypal patients) had smaller volumes of bilateral amygdala and left
      posterior parahippocampal gyrus than patients without it. In the control
      subjects, the large CSP did not affect the volumes of the medial temporal lobe
      structures. These findings might reflect neurodevelopmental abnormalities in
      midline and associated limbic structures of the brain in schizophrenia spectrum.

PMID- 17553606
TI  - Involvement of free radicals followed by the activation of phospholipase A2 in
      the mechanism that underlies the combined effects of methamphetamine and morphine
      on subacute toxicity or lethality in mice: comparison of the therapeutic
      potential of fullerene, mepacrine, and cooling.
AB  - An increase in polydrug abuse is a major problem worldwide. The coadministration
      of methamphetamine and morphine increased subacute toxicity or lethality in
      rodents. However, the underlying mechanisms by which lethality is increased by
      the coadministration of methamphetamine and morphine are not yet fully
      understood. Coadministered methamphetamine and morphine induced lethality by more
      than 80% in BALB/c mice, accompanied by the rupture of cells in the kidney and
      liver, and an increase in poly (ADP-ribose) polymerase (PARP)-immunoreactive
      cells in the heart, kidney and liver. The lethal effect and the increase in the
      incidence of rupture or PARP-immunoreactive cells induced by the coadministration
      of methamphetamine and morphine was significantly attenuated by pretreatment with
      mepacrine (phospholipase A(2) inhibitor) or fullerene (a radical scavenger), or
      by cooling from 30 to 90 min after drug administration. Furthermore, based on the
      results of the electron spin resonance spin-trapping technique, hydroxyl radicals
      were increased by the administration of methamphetamine and morphine, and these
      increased hydroxyl radicals were potently attenuated by fullerene and cooling.
      These results suggest that hydroxyl radicals plays an important role in the
      increased lethality induced by the coadministration of methamphetamine plus
      morphine. The potency of cooling or drugs for decreasing the subacute toxicity or
      lethality induced by the coadministration of methamphetamine and morphine was in
      the order fullerene=cooling>mepacrine. These results indicate that fullerene and
      cooling are beneficial for preventing death that is induced by the
      coadministration of methamphetamine and morphine.

PMID- 17553607
TI  - An in vitro approach to assess the toxicity of certain food contaminants:
      methylmercury and polychlorinated biphenyls.
AB  - Methylmercury (MeHg) and polychlorinated biphenyls (PCBs) are widespread
      environmental pollutants and food contaminants, and known developmental
      neurotoxicants. Aim of this study was to evaluate the effects of MeHg, PCB 126
      and PCB 153 in a battery of in vitro cell systems. A total of 17 cell types were
      utilized, including nervous system (neuronal and astroglial) and non-nervous
      system cells. End-points measured included MTT reduction, Trypan blue exclusion
      and (3)H-thymidine incorporation into DNA. Results indicate that this approach
      would identify these three compounds as neurotoxicants, and would also point out
      to the thyroid (for PCB 126 and MeHg) and the prostate (for both PCBs) as
      important additional targets. Tests of binary combinations of MeHg and PCBs
      indicated no interaction and an additive response, in agreement with other recent
      reports. Cerebellar granule neurons from mice with genetically determined low
      glutathione levels were more sensitive than wild-type neurons to the toxicity of
      all three compounds, supporting a role for oxidative stress in their
      neurotoxicity. These findings provide initial evidence that a relatively rapid in
      vitro screening approach can be developed, that would provide initial information
      useful for assessing neurotoxicity, as well as indication on potential other
      targets of biological action or toxicity.

PMID- 17553608
TI  - In vitro immunotoxicity of bis(tri-n-butyltin)oxide (TBTO) studied by
      toxicogenomics.
AB  - The biocide and environmental pollutant bis(tri-n-butyltin)oxide (TBTO) causes
      thymus atrophy in rodents. Whether the depletion of thymic lymphocytes by
      tributyltin compounds may be the result of inhibition of cell proliferation or
      induction of apoptosis is subject of debate. We examined gene expression profiles
      in primary rat thymocytes exposed to TBTO in vitro at dose levels of 0, 0.1, 0.3,
      0.5, and 1.0microM. By measuring cell viability and apoptosis, exposure
      conditions were selected that would provide information on changes in gene
      expression preceding or accompanying functional effects of TBTO. Several
      processes related to TBTO-induced toxicity were detected at the transcriptome
      level. Effects on lipid metabolisms appeared to be the first indication of
      disruption of cellular function. Many transcriptional effects of TBTO at higher
      dose levels were related to apoptotic processes, which corresponded to present or
      subsequent thymocyte apoptosis observed phenotypically. The gene expression
      profile was, however, not unambiguous since expression of apoptosis-related genes
      was both increased and decreased. Stimulation of glucocorticoid receptor
      signaling appeared to be a relevant underlying mechanism of action. These
      findings suggest that TBTO exerts its toxic effects on the thymus primarily by
      affecting apoptotic processes, but the possibility is discussed that this may in
      fact represent an early effect that precedes inhibition of cell proliferation. At
      the highest dose level tested, TBTO additionally repressed mitochondrial function
      and immune cell activation. Our in vitro toxicogenomics approach thus identified
      several cellular and molecular targets of TBTO that may mediate the toxicity
      towards thymocytes and thereby its immunosuppressive effects.

PMID- 17553609
TI  - Trauma surgeons' attitude towards family presence during trauma resuscitation: a
      nationwide survey.
AB  - OBJECTIVE: Trauma is the foremost cause of death in young patients. Not only the
      patient but also the family experience the consequences of trauma. Interactions
      of medical staff with family members in the emergency situation may fail
      psychological and emotional needs. In this context the concept of family presence
      (FP) during resuscitation is controversial. Therefore, the aim of this study was
      to analyse the attitude of trauma surgeons towards FP during trauma
      resuscitation. MATERIALS AND METHODS: A questionnaire concerning beliefs and
      attitudes towards FP during trauma resuscitation was mailed to level I trauma
      centres of the Trauma Network of the German Trauma Society (DGU). Statistical
      difference was determined by Rank-Sum test to analyse ordinal variables, for
      analysing three groups Kruskal-Wallis and Dunn's testing were used. Data are
      given in mean+/-S.D. or absolute percentage. RESULTS: The questionnaire was
      answered by 464 of 545 (85%) trauma surgeons between July 2005 and September
      2005. One hundred and sixty seven surgeons (37.9%) already knew about FP, 349
      (75.2%) considered it a relevant topic, but 232 (50%) would never allow FP during
      trauma resuscitation. One hundred and sixty eight surgeons (36.2%) had experience
      of FP during trauma resuscitation with positive results in 56%. Female
      respondents tend to be better informed about FP and would promote FP more
      supportively. Those women with experience with FP reported predominantly positive
      experiences (87% versus 50%, p<0.001). CONCLUSIONS: Our study investigated the
      factors affecting physicians' opinions towards FP. Any institutional FP programme
      will have to address physician objections to be successful, by recommending a
      well-designed, carefully structured protocol with a designated specially trained
      staff member to offer the family support and the option of entering the
      resuscitation room with permission of the staff.

PMID- 17553610
TI  - Efficacy of therapeutic hypothermia after out-of-hospital cardiac arrest due to
      ventricular fibrillation.
AB  - AIM OF THE STUDY: We investigated implementation and efficacy of mild therapeutic
      hypothermia in the treatment of out-of-hospital cardiac arrest due to ventricular
      fibrillation. MATERIALS AND METHODS: Two periods were compared, an historical one
      (36 patients) between 2000 and 2002 where therapeutic hypothermia was never used,
      and a recent period (32 patients) between 2003 and 2005 where therapeutic
      hypothermia (32-34 degrees C) was implemented prospectively in our unit. Cooling
      was obtained by simply using wet cloths and ice packs. Survival in the two groups
      and factors associated with survival were analysed, together with the
      neurological prognosis in discharged patients. RESULTS: Survival was
      significantly higher in the hypothermia group (56% versus 36%), whereas no
      significant difference was observed in severity between the two periods. Only
      age, time from return to spontaneous circulation <20min, and therapeutic
      hypothermia were independently associated with survival. Therapeutic hypothermia
      was well tolerated and was associated with a significant improvement in
      neurological outcome. Whereas only 23% of patients actually reached the target
      temperature in 2003, 100% did in 2005. CONCLUSION: Therapeutic hypothermia is
      efficient in significantly improving survival and neurological outcome of out-of
      hospital cardiac arrest with ventricular fibrillation. By using a simple method,
      it can be implemented easily and quickly, without side effects.

PMID- 17553611
TI  - Presumed futility in paramedic-treated out-of-hospital cardiac arrest: an Utstein
      style analysis in Tampere, Finland.
AB  - AIM: To report prospectively the outcome from prehospital cardiac arrest
      according to the Utstein template in the city of Tampere, Finland, with special
      reference to those patients in whom resuscitation was not attempted. MATERIALS
      AND METHODS: In Tampere (population 203,000), a two-tiered emergency medical
      service (EMS) system provides first response and basic life support (BLS),
      supported by advanced life support (ALS) units staffed with nurse-paramedics. We
      analysed all out-of-hospital cardiac arrests considered for resuscitation during
      a 12-month period. RESULTS: Of 191 patients with prehospital cardiac arrest,
      resuscitation was not attempted in 98 patients (51%). Reasons to withhold from
      resuscitation were estimated futility (97 cases) and a do-not-attempt
      resuscitation order (1). Sixty percent of the patients with no resuscitation had
      secondary signs of death, 97% had asystole as the initial cardiac rhythm and 98%
      had suffered an unwitnessed cardiac arrest. Resuscitation was successful in 45 of
      the remaining 93 patients with attempted resuscitation. Twelve patients were
      discharged (overall survival rate 13%), nine of them with a CPC score of 1 or 2.
      Fifteen patients were treated with therapeutic hypothermia. Of the bystander
      witnessed cardiac arrests with VF as initial rhythm, 29% survived. CONCLUSIONS:
      The Tampere EMS system initiated resuscitation less frequently than reported from
      other EMS systems, but the reasons to withhold resuscitation seemed justified.
      The overall and Utstein's 'golden standard' survival rates were comparable with
      previous reports.

PMID- 17553612
TI  - Tumor necrosis factor promotes T-cell at the expense of B-cell lymphoid
      development from cultured human CD34+ cord blood cells.
AB  - OBJECTIVE: Human CD34+ cord blood (CB) cells are hematopoietic progenitors useful
      for stem cell transplantation, even after ex vivo expansion. We investigated the
      effect of tumor necrosis factor (TNF) on lymphoid development from cultured CD34+
      CB cells. MATERIALS AND METHODS: Human CD34+ CB cells were cultured in cytokine
      mixes with or without TNF. Preculture during 60 hours was followed by in vitro
      differentiation assays, including fetal thymus organ culture and coculture on
      murine stromal MS-5 cells. In a next step, experiments were extended to CD34+CD38
      and CD34+CD38+ CB cells and prolonged preculture. RESULTS: Preculture in the
      presence of TNF improved differentiation into T cells and diminished the ability
      to generate B cells, while NK potential and myeloid development were unaffected.
      Sorted CD34+CD38- CB cells were more potent T-cell precursors after preculture in
      TNF, compared to CD34+CD38+ CB cells. In precultured CD34+CD38- CB cells, TNF
      increased GATA3 but decreased EBF1 expression, in line with the skewed lymphoid
      differentiation induced by TNF. However, when preculture in the presence of TNF
      was extended to 1 week, T-cell precursors were lost. CONCLUSION: After short-term
      culture of CD34+ CB cells in the presence of TNF, T-cell generation is stimulated
      at the expense of B-cell generation. T-cell progenitors are enriched in the
      CD34+CD38- fraction. These results have implications on the culture conditions to
      be used for CB CD34+ cells prior to transplantation.

PMID- 17553613
TI  - Transplant conditions determine the contribution of homeostatically expanded
      donor CD8 memory cells to host lymphoid reconstitution following syngeneic HCT.
AB  - OBJECTIVE: To investigate the ability of donor CD8 memory (CD8 TM) cells to
      expand in recipients following syngeneic hematopoietic stem cell transplants
      (HCT). The influence of clinically important transplant parameters--conditioning
      level, delayed infusion and dose--on the homeostatic expansion and overall
      contribution of donor CD8 TM to host CD8 reconstitution was determined. MATERIALS
      AND METHODS: Lymphopenia-induced CD8 TM homeostatic expansion was examined in a
      syngeneic murine HCT model. Antigen specific CD8 TM included both T-cell receptor
      transgenic and nontransgenic populations. An ex vivo technique using antigen,
      interleukin (IL)-2, and IL-15 was used to generate homogenous transgenic CD8 TM
      (i.e., central memory) and was adapted to enrich the heterogeneous nontransgenic
      CD8 population specific for a nonameric epitope. RESULTS: Both transgenic and
      naturally occurring CD8 memory populations, derived in vivo or generated ex vivo,
      underwent a similar kinetic pattern of homeostatic expansion following
      transplantation into ablatively conditioned syngeneic recipients. Transplant
      parameters, i.e., lower conditioning, delayed infusion, and lower donor CD8 cell
      numbers shortened the period of expansion and lowered the steady-state numbers.
      CONCLUSIONS: The pattern of CD8 TM expansion was dependent on conditioning
      levels, time of infusion, and dose. Transplantation of varying donor CD8 TM
      numbers demonstrated there was a maximal donor cell contribution to host CD8
      reconstitution. The application of multiple well-defined memory CD8 populations
      supports the notion that these findings are characteristic of memory CD8 cells in
      general.

PMID- 17553615
TI  - Adeno-associated viral delivery of a metabolically regulated insulin transgene to
      hepatocytes.
AB  - Transduction with a liver specific, metabolically responsive insulin transgene
      produces near-normal blood sugars in STZ-diabetic rats. To overcome the limited
      duration of hepatic transgene expression induced by E1A-deleted adenoviral
      vectors, we evaluated recombinant adeno-associated virus (rAAV2) for cell type
      specificity and glucose responsiveness in vitro. Co-infection of AAV2 containing
      the glucose responsive, liver-specific (GlRE)(3)BP-1 promoter with an empty
      adenovirus enhanced transduction efficiency, and shortened the duration of
      transgene expression in HepG2 hepatoma cells, but not primary hepatocytes.
      However, in the context of rAAV2, (GlRE)(3)BP-1 promoter activity remained
      confined to cells of hepatocyte lineage, and retained glucose responsiveness.
      While isolated infection with an insulin expressing rAAV2 failed to attenuate
      blood sugars in diabetic mice, adenoviral co-administration with the same rAAV2
      induced transient, near-normal random blood sugars in a diabetic animal. We
      conclude that rAAV2 can induce metabolically responsive insulin secretion from
      hepatocytes in vitro and in vivo. However, alternative AAV serotypes will likely
      be required to efficiently deliver therapeutic genes to the liver for the
      treatment of diabetes mellitus.

PMID- 17553614
TI  - Unique and redundant roles of alpha4 and beta2 integrins in kinetics of
      recruitment of lymphoid vs myeloid cell subsets to the inflamed peritoneum
      revealed by studies of genetically deficient mice.
AB  - OBJECTIVE: Leukocyte recruitment to inflammatory sites is a prominent feature of
      acute and chronic inflammation. Instrumental in this process is the coordinated
      upregulation of leukocyte integrins (among which alpha4beta1 and beta2 integrins
      are major players) and their cognate receptors in inflamed tissues. To avoid the
      ambiguity of previous short-term antibody-based studies and to allow for long
      term observation, we used genetically deficient mice to compare roles of alpha4
      and beta2 integrins in leukocyte trafficking. MATERIALS AND METHODS: Aseptic
      peritonitis was induced in alpha4 or beta2 integrin-deficient (conditional and
      conventional knockouts, respectively) and control mice, and recruitment of major
      leukocyte subsets to the inflamed peritoneum was followed for up to 4 days.
      RESULTS: Despite normal chemokine levels in the peritoneum and adequate numbers,
      optimal recruitment of myeloid cells was impaired in both alpha4- and beta2
      deficient mice. Furthermore, clearance of recruited neutrophils and macrophages
      was delayed in these mice. Lymphocyte migration to the peritoneum in the absence
      of alpha4 integrins was drastically decreased, both at steady state and during
      inflammation, a finding consistent with impaired lymphocyte in vitro adhesion and
      signaling. By contrast, in the absence of beta2 integrins, defects in lymphocyte
      recruitment were only evident when peritonitis was established. CONCLUSIONS: Our
      data with concurrent use of genetic models of integrin deficiency reveal
      nonredundant functions of alpha4 integrins in lymphocyte migration to the
      peritoneum and further refine specific roles of alpha4 and beta2 integrins
      concerning trafficking and clearance of other leukocyte subsets at homeostasis
      and during inflammation.

PMID- 17553616
TI  - Cell killing by antibody-drug conjugates.
AB  - Antibody-drug conjugates (ADCs) are designed to specifically bind to and kill
      cells expressing their target antigens. In addition to the obvious requirement of
      the presence of the target antigen on the cell surface, several other factors
      contribute to the sensitivity of target cells to the action of ADCs. These
      include (i) the rate of internalization of the ADC, (ii) its proteolytic
      degradation in late endosomes and lysosomes and the subsequent release of
      cytotoxic drug, and (iii) the intracellular concentration of the released drug.
      In addition to killing antigen-expressing cells, some ADCs were found to kill
      bystander cells irrespective of their antigen expression. This review summarizes
      the current knowledge of the mechanisms of killing of antigen-expressing and
      bystander cells by antibody-drug conjugates.

PMID- 17553617
TI  - Mechanism of caspase-3 activation during hypoxia in the cerebral cortex of
      newborn piglets.
AB  - We have previously shown that the activity and the expression of caspase-9 and
      caspase-3 were increased during hypoxia in the cerebral cortex of newborn
      piglets. The present study was conducted to test the hypothesis that the hypoxia
      induced activation of caspase-3 in the cerebral cortex of newborn piglets is
      mediated by caspase-9. Twenty-two newborn piglets were randomly assigned to four
      groups: normoxic (Nx), normoxic pretreated with a selective caspase-9 inhibitor,
      Z-Leu-Glu(OMe)-His-Asp(OMe)-Fluoromethyl ketone (Z-LEHD-FMK) (Nx+LEHD), hypoxic
      (Hx), and hypoxic pretreated with Z-LEHD-FMK (Hx+LEHD). Cerebral tissue hypoxia
      was confirmed biochemically by measuring ATP and phosphocreatine. Caspase-9 and 
      3 activities were determined spectrofluorometrically. The expression of caspase-9
      and -3 proteins was measured by Western blot analysis using active enzyme
      specific antibodies. Cytosolic caspase-9 activity (nmol/mg protein/h) was 3.70+/
      0.40 in Nx, 3.56+/-0.31 in Nx+LEHD (p=NS versus Nx), 4.99+/-0.64 in Hx (p<0.05
      versus Nx), and 3.73+/-0.80 in Hx+LEHD (p<0.05 versus Hx, p=NS versus Nx).
      Cytosolic caspase-3 activity (nmol/mg protein/h) was 7.80+/-1.17 in Nx, 8.15+/
      0.87 in Nx+LEHD (p=NS versus Nx), 13.07+/-0.78 in Hx (p<0.05 versus Nx), and
      10.05+/-2.09 in Hx+LEHD (p<0.05 versus Hx) The density (ODxmm(2)) of active
      caspase-9 protein was 18.52+/-1.89 in Nx, 20.53+/-1.12 in Nx+LEHD (p=NS versus
      Nx), 32.36+/-5.03 in Hx (p<0.05 versus Nx), and 19.94+/-3.59 in Hx+LEHD (p<0.05
      versus Hx, p=NS versus Nx). The density (ODxmm(2)) of active caspase-3 protein
      was 55.87+/-8.73 in Nx, 55.69+/-8.18 in Nx+LEHD (p=NS versus Nx), 94.10+/-12.05
      in Hx (p<0.05 versus Nx), and 56.12+/-14.56 in Hx+LEHD (p<0.05 versus Hx, p=NS
      versus Nx). These data show that administration of a selective caspase-9
      inhibitor, Z-LEHD-FMK, prior to hypoxia prevents the hypoxia-induced increase in
      caspase-3 activity and the expression of active caspase-3 protein. We conclude
      that the hypoxia-induced activation of caspase-3 during hypoxia in the cerebral
      cortex of newborn piglets is mediated by caspase-9.

PMID- 17553618
TI  - Hydrogen sulfide, is it a promise analgesic drug or another inflammatory pain
      mediator?

PMID- 17553620
TI  - Wetting study of patterned surfaces for superhydrophobicity.
AB  - Superhydrophobic surfaces have considerable technological potential for various
      applications due to their extreme water-repellent properties. A number of studies
      have been carried out to produce artificial biomimetic roughness-induced
      hydrophobic surfaces. In general, both homogeneous and composite interfaces are
      possible on the produced surface. Silicon surfaces patterned with pillars of two
      different diameters and heights with varying pitch values were fabricated. We
      show how static contact angles vary with different pitch values on the patterned
      silicon surfaces. Based on the experimental data and a numerical model, the
      trends are explained. We show that superhydrophobic surfaces have low hysteresis
      and tilt angle. Tribological properties play an important role in many
      applications requiring water-repellent properties. Therefore, it is important to
      study the adhesion and friction properties of these surfaces that mimic nature.
      An atomic/friction force microscope (AFM/FFM) is used for surface
      characterization and adhesion and friction measurements.

PMID- 17553621
TI  - Colorectal cancer screening in elderly patients: when should be more useful?
AB  - Current guidelines endorse colon cancer screening every 5-10 years in persons
      over 50 years of age. However, there is no consensus regarding what age is
      appropriate to stop screening. Prior history of neoplasia seems to be a strong
      risk factor for colorectal neoplasia development in elderly people and should be
      considered when deciding the need for continuing screening/surveillance, however,
      clinical judgment of comorbidities is still required to individualize screening
      practice. Screening colonoscopy in very elderly persons (aged 80 years), i.e.
      should be performed only after careful consideration of potential benefits, risks
      and patient preferences. The aims of this paper are to: (1) determine the best
      type of colorectal cancer screening (faecal occult blood testing, flexible
      sigmoidoscopy, double-contrast barium enema and colonoscopy) and its association
      with age and health status among elderly veterans and (2) describe the outcomes
      of colorectal cancer screening among older veterans who have widely differing
      life expectancies (based on age and health status).

PMID- 17553622
TI  - Early maternal deprivation and neonatal single administration with a cannabinoid
      agonist induce long-term sex-dependent psychoimmunoendocrine effects in
      adolescent rats.
AB  - Maternal deprivation [24h on postnatal day 9] might represent an animal model of
      schizophrenia and behavioural and neurochemical alterations observed in adulthood
      may be mediated by hippocampal impairments induced by abnormally increased
      glucocorticoids due to neonatal stress. We aimed to provide new data for
      psychoimmunoendocrine characterization of this animal model by evaluating its
      effects in adolescent rats of both genders. In previous studies we found that
      cannabinoid compounds counteracted the enhanced impulsivity of maternally
      deprived animals and that the cannabinoid receptor agonist WIN 55,212-2 showed
      neuroprotective properties in neonatal rats. So, we hypothesised that this
      compound could counteract at least some of the detrimental effects that we
      expected to find in maternally deprived animals. Accordingly, the drug was
      administered immediately after the maternal deprivation period. Maternally
      deprived males showed significantly decreased motor activity in the holeboard and
      the plus-maze. The cannabinoid agonist induced, exclusively in males, a
      significant anxiogenic-like effect, which was reversed by maternal deprivation.
      In the forced swimming test, both treatments independently induced depressive
      like responses. Maternal deprivation reduced immunological function whereas the
      drug exerted tissue-dependent effects on the immune parameters analysed.
      Maternally deprived females showed reduced corticosterone levels whereas the
      cannabinoid agonist increased hormone concentration in all groups. In general,
      the results show detrimental effects of both treatments as well as intriguing
      interactions, notably in relation to emotional behaviour and certain
      immunological responses.

PMID- 17553623
TI  - Premature mortality among males with substance use disorders.
AB  - OBJECTIVE: Previous studies have demonstrated that substance use disorders (SUD)
      are associated with premature mortality in clinical populations, though findings
      regarding the effect of antisocial personality disorder (ASP) on mortality among
      persons with SUD are less clear. However, it is unclear to what extent that
      finding generalizes to persons with SUD in the community, because very little
      work has been done involving mortality in longitudinal studies of mortality
      associated with SUD. The objective of this study was to assess whether the
      presence of SUD or ASP is associated with early mortality among males (fathers)
      in a predominantly community sample, using a 15-year prospective longitudinal
      study design. METHOD: We conducted a prospective longitudinal study of
      adolescents and their fathers. The adolescent subjects were recruited at age 10
      12 years, with follow-up evaluations at ages 14, 16, 19, 22, and 25. Questions
      were asked about paternal mortality during each of those visits. The study sample
      for this study was the 769 fathers of the adolescent subjects, who included N=341
      fathers with a DSM-III-R diagnosis of SUD and N=428 control fathers without a
      SUD. 89% of these fathers were recruited from the community, and 11% were
      recruited from clinical sources. Comorbidity patterns were described. A
      multivariate Cox regression analysis was performed with the father's age at death
      or last assessment as the dependent variable, and education, SUD, and ASP as the
      independent variables. RESULTS: Lower education level, the presence of a
      substance use disorder, and the presence of antisocial personality disorder were
      significantly associated with earlier mortality (Wald=5.1, df=1, p=0.024;
      Wald=5.1, df=1, p=0.024, and Wald=5.5, df=1, p=0.019, respectively). Most
      subjects died from medical illnesses, as opposed to drug overdoses or accidents,
      which is different from the pattern often noted in clinical samples. CONCLUSIONS:
      The results of this study demonstrate that the presence of SUD, the presence of
      ASP, and a lower education level were associated with early mortality in our
      primarily community-based sample, which extends previous reports of similar
      findings in clinical samples. The magnitude of the prematurity of the deaths was
      less that that generally noted in previous studies involving clinical samples,
      and the causes of death were also somewhat different from those noted in clinical
      samples. The majority of cases of mortality in our SUD sample resulted from
      medical illnesses rather than from accidents or overdoses.

PMID- 17553624
TI  - Use of commercial and social sources of alcohol by underage drinkers: the role of
      pubertal timing.
AB  - We have explored whether alcohol use and procurement of alcohol from commercial
      and social sources vary with pubertal timing. A sub-sample of 9291 Norwegian
      minors (13-17 year-olds) was extracted from a nationwide school survey (response
      rate: 92%). Adolescents who had matured early (early developers, EDs) reported
      higher consumption and more alcohol-related harm than those who had matured late
      (late developers, LDs) or at the "normal" time (on time developers, ODs).
      Purchases from on-premise and off-premise outlets were much more important
      sources of alcohol for EDs than for ODs and LDs - both in relative and absolute
      terms. Moreover, EDs were somewhat more likely to obtain alcohol from social
      sources. Taken together, the findings indicate that adolescents who mature early
      have access to a larger variety of sources of alcohol than adolescents who mature
      later - which in turn may explain their increased level of drinking.

PMID- 17553625
TI  - Phagotrophic protozoa: A new weapon against pathogens?
AB  - Immune suppression is one of the most important factors contributing mortality in
      systemic diseases like HIV, cancer or diabetes. Moreover, in autoimmune diseases
      immune suppression itself becomes the only choice of therapy. Finally, fatal
      bacterial infections occur. As antibiotics get stronger, severity of their side
      effects increase and more resistant organisms develop. The war between
      antibiotics and pathogens becomes a never ending story while human body gets
      weaker day by day. Therefore we should develop new methods against bacterial
      infections. We have suggested that the protists controlling the bacterial growth
      effectively in aquatic environments could be used in the human body to cope with
      human pathogens. Million years of a balanced aquatic ecosystem could be a clue
      for us to search for better and more natural fighting methods against human
      infectious agents.

PMID- 17553626
TI  - Thyrotropin-releasing hormone (TRH) in the neuroaxis: therapeutic effects reflect
      physiological functions and molecular actions.
AB  - Nearly four decades of research have yielded thousands of publications on the
      physiology, pharmacology and therapeutic effects of TRH and TRH mimetic analogs.
      This work addresses both the neuroendocrine and the extrahypothalamic actions and
      functions of the tripeptide. The many reports of clinical effects of TRH in
      diverse medical conditions, unrelated to pituitary or thyroid function, can
      appear bewildering, as can its widespread involvement in a plethora of neuronal
      and physiological processes. Herein, we hypothesize that a logical and causal
      interrelationship exists between the fundamental molecular and cellular actions
      of TRH, its broader physiological functions and the therapeutic effects that
      attend the administration of exogenous TRH and TRH analogs. When viewed from this
      perspective, the basic neurobiological actions and functions of TRH provide a
      rational basis for understanding its diverse therapeutic effects. We posit: that
      the fundamental excitatory actions of TRH throughout the neuroaxis result from
      blocking various K+ channels linked to G-protein coupled TRH receptors in neurons
      and pituitary cells in distinct TRH-innervated anatomical pathways; that the
      functional consequences of blockade of these K+ channels are to enhance neuronal
      and secretory outputs in TRH regulatory circuits to modulate behavioral and
      energy homeostasis, and; that in clinical situations the resultant broad and
      useful therapeutic effects following administration of TRH reflect the state
      dependent normalizing effects of activation of these regulatory circuits. In this
      light, the spectrum of reported clinical effects of TRH agonism remains unique
      and impressive but is less enigmatic. With the understanding that the
      neurobiological actions of TRH underlie and are rationally antecedent to its
      documented, extensive clinical 'normotrophic' effects, continued empirical
      efforts to assess the medical uses of TRH and related drugs seem rational and
      warranted. We predict that the range of disorders whose symptoms are alleviated
      by TRH therapy will continue to expand and that TRH agonism could conceivably
      become a near-universal therapeutic adjunct, particularly in the practice of
      neuropsychiatric medicine.

PMID- 17553627
TI  - Bioinformatics analysis of functional protein sequences reveals a role for brain
      derived neurotrophic factor in obesity and type 2 diabetes mellitus.
AB  - Using bioinformatics techniques and sequence analyses algorithms, a comparative
      study between human and rodents revealed similarity in the behavior of genes
      involved in the control of energy homeostasis. Brain-derived neurotrophic factor
      (BDNF) modulates the secretion and actions of insulin, leptin, ghrelin, various
      neurotransmitters and peptides, and pro-inflammatory cytokines involved in energy
      homeostasis suggesting that it (BDNF) has a significant role in the pathobiology
      of obesity and type 2 diabetes mellitus. Based on these evidences, we propose
      that obesity and type 2 diabetes could be disorders of the brain and BDNF could
      serve as a biomarker in predicting their development. Hence, methods developed to
      selectively deliver BDNF to appropriate hypothalamic neurons may form a novel
      approach in their treatment.

PMID- 17553628
TI  - Erythropoietin and Parkinson's disease: Suggested mechanisms and therapeutic
      implications.

PMID- 17553629
TI  - Elevated butyrylcholinesterase and acetylcholinesterase may predict the
      development of type 2 diabetes mellitus and Alzheimer's disease.
AB  - Plasma levels of C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis
      factor-alpha (TNF-alpha), and lipid peroxides are elevated and concentrations of
      endothelial nitric oxide (eNO) decreased in type 2 diabetes mellitus and
      Alzheimer's disease. This suggests that both these diseases are low-grade
      systemic inflammatory conditions and are closely associated with each other.
      Recent studies revealed that plasma and tissue concentrations of enzymes
      butyrylcholinesterase and acetylcholinesterase are elevated in type 2 diabetes
      and Alzheimer's disease. Acetylcholine has anti-inflammatory actions. Hence,
      elevated butyrylcholinesterase and acetylcholinesterase concentrations will lead
      to a decrease in the levels of acetylcholine that could trigger the onset of low
      grade systemic inflammation seen in type 2 diabetes and Alzheimer's disease. In
      view of this, we propose that butyrylcholinesterase and acetylcholinesterase will
      not only serve as therapeutic targets but also may serve as markers to predict
      the development of type 2 diabetes mellitus and Alzheimer's disease.

PMID- 17553630
TI  - Are xenogeneic anti-tissue transglutaminase antibodies the holy grail for celiac
      patients?
AB  - Celiac disease is an immune mediated disorder, the only one with a well
      established origin, resulting from a permanent gluten intolerance. Although a
      gluten-free diet is currently the "safe" and appropriate therapy for celiac
      disease, this is not always an easy and simple option as "harmful" gluten may
      contaminate food during the processing and preparation phases. There are also
      further social pressures, which might be more pressing for young celiac patients,
      in following a strict gluten-free diet. Therefore, a new therapeutic approaches
      are sought which would permit celiacs to "peacefully" coexist with gluten.
      Presently, the most promising looks search for genetically modified wheat lacking
      toxic gluten peptides and the use of oral endopeptidases in attempt to curb
      gluten toxicity. Recently discovered role of anti-tissue transglutaminase
      antibodies in celiac pathogenesis has brought a prospect for a new hypothetical
      therapeutic approach, an oral immunization of celiacs with xenogeneic anti-tissue
      transglutaminase antibodies.

PMID- 17553631
TI  - Ozoroalide, a new macrolide from Ozoroa insignis.
AB  - From the roots of Ozoroa insignis a new orsellinic acid named ozoroalide (1) and
      anacardic acid methyl ester (2) were isolated and identified on the basis of
      spectroscopic methods.

PMID- 17553632
TI  - Cytoprotective effect of Panax ginseng on gallic acid-induced toxicity in TM3
      mouse Leydig cells.
AB  - Our previous study had demonstrated cytotoxicity of gallic acid on testicular
      cells with increasing the intracellular production of hydrogen peroxide. In the
      present study, the Panax ginseng root aqueous extract showed the cytoprotective
      effect on gallic acid-induced toxicity in TM3 mouse Leydig cells with decreasing
      the intracellular production of hydrogen peroxide.

PMID- 17553633
TI  - Antibacterial activities of some mosses including Hylocomium splendens from South
      Western British Columbia.
AB  - The antibacterial activity of methanol extracts of ten moss species and fractions
      prepared from 80% methanol extract of Hylocomium splendens were evaluated by disk
      diffusion method. Nine moss species showed antibacterial activity against Gram
      (+) bacteria, in particular H. splendens and its ethyl acetate fractions showed
      stronger activity. Enhancement of antibacterial activity against Staphylococci by
      UV-A light irradiation was demonstrated in the extracts of Bartramia pomiformis,
      Ceratodon purpureus and Neckera douglasii.

PMID- 17553634
TI  - Bacteriostatic effect of flavonoids isolated from leaves of Psidium guajava on
      fish pathogens.
AB  - The antimicrobial activity against fish bacterial pathogens of flavonoids (morin,
      morin-3-O-lyxoside, morin-3-O-arabinoside, quercetin, and quercetin-3-O
      arabinoside) isolated from the leaves of Psidium guajava was evaluated. The
      flavonoids were shown to have bacteriostatic effect on all of the tested
      bacteria.

PMID- 17553636
TI  - Behavioral and economic perspectives in drug abuse research.

PMID- 17553635
TI  - On the development of nicotine dependence in adolescence.
AB  - Little is known about the natural history of drug dependence. This article
      describes the development and predictors of DSM-IV nicotine dependence in
      adolescence when tobacco use is initiated. In a two-stage design, a survey was
      administered to 6th-10th graders in the Chicago Public Schools to select a cohort
      of adolescents. Household interviews were conducted with adolescents five times
      and with one parent (predominantly mothers) three times over 2 years. The
      analytical sample includes 353 youths, who started using tobacco within 12 months
      preceding Wave 1 or between Waves 1-5. Survival analysis estimated latency to
      individual DSM-IV nicotine dependence criteria and the full dependence syndrome.
      Twenty-five percent of youths experienced the syndrome within 23 months of
      tobacco use onset. Tolerance, impaired control and withdrawal were experienced
      most frequently. Youths who developed full dependence experienced their first
      symptom faster after tobacco use onset than those who experienced only one
      criterion through the end of the observation period. Cox proportional hazards
      models estimated the importance of time-constant and time-varying
      sociodemographic, tobacco and other drug use, parental and peer smoking, social
      psychological and biological risk factors for experiencing the first criterion
      and the full syndrome. Pleasant initial sensitivity to tobacco and number of
      cigarettes smoked the prior month predicted both outcomes. Parental dependence
      predicted the full syndrome. Significant covariates were generally the same
      across gender and racial/ethnic subgroups. The predictive significance of the
      initial smoking experience and parental dependence highlight the potential
      importance of genetic factors in the etiology of nicotine dependence.

PMID- 17553637
TI  - Biogeography and adaptation of Notothenioid fish: hemoglobin function and globin
      gene evolution.
AB  - The recognition of the important role of the polar habitats in global climate
      changes has awakened great interest in the evolutionary biology of polar
      organisms. They are exposed to strong environmental constraints, and it is
      important to understand how they have adapted to cope with these challenges and
      to what extent adaptations may be upset by current climate changes. We present an
      introductory overview of the evolution of the Antarctic fish fauna with emphasis
      on the dominant perciform sub-order Notothenioidei, as well as some specific
      comments on the biogeography of the three phyletically basal notothenioid
      families. The wealth of information on the ecology and biodiversity of the
      species inhabiting high-Antarctic and sub-Antarctic regions provides a necessary
      framework for better understanding the origin, evolution and adaptation of this
      unique group of fish. Notothenioidei offer opportunities for identification of
      the biochemical characters or the physiological traits responsible for thermal
      adaptation. The availability of phylogenetically related taxa in a wide range of
      latitudes has allowed to look into the molecular bases of environmentally driven
      phenotypic gain and loss of function. In the process of cold adaptation, the
      evolutionary trend of notothenioids has produced unique specialisations,
      including modification of hematological characteristics, e.g. decreased amounts
      and multiplicity of hemoglobins. The Antarctic family Channichthyidae (the
      notothenioid crown group) is devoid of hemoglobin. This loss is related to a
      single deletional event removing all globin genes with the exception of the
      inactive 3' end of adult alpha-globin. In reviewing hemoglobin structure,
      function and phylogeny, the evolution of the fish Root effect is analysed in
      detail. Adaptation of the oxygen-transport system in notothenioids seems to be
      based on evolutionary changes involving levels of biological organisation higher
      than the structure of hemoglobin.

PMID- 17553638
TI  - Functional diversification of kir7.1 in cichlids accelerated by gene duplication.
AB  - Mutation in the inward rectifier potassium channel gene, kir7.1, was previously
      identified as being responsible for the broader stripe zebrafish skin pattern
      mutant, jaguar/obelix. An amino acid substitution in this channel causes a
      broader stripe pattern than that of wild type zebrafish. In this study we
      analyzed cichlid homologs of the zebrafish kir7.1 gene. We identified two kinds
      of homologous genes in cichlids and named them cikir7.1 and cikir7.2. Southern
      hybridization using cichlid genome revealed that cichlids from the African Great
      Lakes, South America and Madagascar have two copies of the gene. Cichlids from
      Sri Lanka, however, showed only one band in this experiment. Database analysis
      revealed that only one copy of the kir7.1 gene exists in the genomes of the
      teleosts zebrafish, tetraodon, takifugu, medaka and stickleback. The deduced
      amino acid sequence of cikir7.1 is highly conserved among African cichlids,
      whereas that of cikir7.2 has several amino acid substitutions even in conserved
      transmembrane domains. Gene expression analysis revealed that cikir7.1 is
      expressed specifically in brain and eye, and cikir7.2 in testis and ovary;
      zebrafish kir7.1, however, is expressed in brain, eye, skin, caudal fin, testis
      and ovary. These results suggest that gene duplication of the cichlid kir7.1
      occurred in a common ancestor of the family Cichlidae, that the function of
      parental kir7.1 was then divided into two genes, cikir7.1 and cikir7.2, and that
      the evolutionary rate of cikir7.2 might have been accelerated, thereby effecting
      functional diversification in the cichlid lineage. Thus, the evolution of kir7.1
      genes in cichlids provides a typical example of gene duplication--one gene is
      conserved while the other becomes specialized for a novel function.

PMID- 17553639
TI  - BfCBR: a cannabinoid receptor ortholog in the cephalochordate Branchiostoma
      floridae (Amphioxus).
AB  - A gene encoding an ortholog of vertebrate CB(1)/CB(2) cannabinoid receptors was
      recently identified in the urochordate Ciona intestinalis (CiCBR; [Elphick, M.R.,
      Satou, Y., Satoh, N., 2003. The invertebrate ancestry of endocannabinoid
      signalling: an orthologue of vertebrate cannabinoid receptors in the urochordate
      Ciona intestinalis. Gene 302, 95-101.]). Here a cannabinoid receptor ortholog
      (BfCBR) has been identified in the cephalochordate Branchiostoma floridae. BfCBR
      is encoded by a single exon and is 410 amino acid residue protein that shares 28%
      sequence identity with CiCBR and 23% sequence identity with human CB(1) and human
      CB(2). The discovery of BfCBR and CiCBR and the absence of cannabinoid receptor
      orthologs in non-chordate invertebrates indicate that CB(1)/CB(2)-like
      cannabinoid receptors originated in an invertebrate chordate ancestor of
      urochordates, cephalochordates and vertebrates. Furthermore, analysis of the
      relationship of BfCBR and CiCBR with vertebrate CB(1) and CB(2) receptors
      indicates that the gene/genome duplication that gave rise to CB(1) and CB(2)
      receptors occurred in the vertebrate lineage. Identification of BfCBR, in
      addition to CiCBR, paves the way for comparative analysis of the expression and
      functions of these proteins in Branchiostoma and Ciona, respectively, providing
      an insight into the ancestral functions of cannabinoid receptors in invertebrate
      chordates prior to the emergence of CB(1) and CB(2) receptors in vertebrates.

PMID- 17553640
TI  - Phenotypic and molecular epidemiologic evaluation of a Nocardia farcinica
      mastitis epizootic.
AB  - Nineteen putative Nocardia farcinica isolates epidemiologically associated with
      intramammary products containing neomycin were obtained from clinical cases in a
      Canada-wide mastitis epizootic. Epidemiologic investigations were unable to
      identify the mechanism for transmission. To evaluate the hypotheses generated
      (intrinsic versus extrinsic contamination) and to confirm the identity of N.
      farcinica, we compared these isolates phenotypically (biochemicals and
      antimicrobial susceptibility studies) and genotypically (16S rRNA gene sequencing
      analysis, chromosomal DNA and ribotyping profiles) with the type and reference
      strains of N. farcinica. Results of biochemical studies and 16S rRNA gene
      sequencing identified the isolates as N. farcinica. Results of chromosomal DNA
      and ribotyping profiles and antimicrobial resistance to amikacin indicated all
      were a unique clone of N. farcinica that differed from the control isolates. Our
      study suggests the epizootic was caused by transmission of a unique clone of N.
      farcinica through intrinsically contaminated dry cow intramammary products rather
      than an extrinsic source.

PMID- 17553641
TI  - Preventive effects of bicarbonate on cerivastatin-induced apoptosis.
AB  - Although HMG-CoA reductase inhibitors such as statins are the most widely used
      cholesterol-lowering agents, there is a risk of myopathy or rhabdmyolysis
      occurring in patients taking these drugs. It has been reported that a number of
      lipophilic statins cause apoptosis in various cells, but it is still not clear
      whether intracellular acidification is involved in statin-induced apoptosis.
      There have been few studies aimed at identifying compounds that suppress statin
      induced myotoxicity. In the present study, we examined the relationship between
      cerivastatin-induced apoptosis and intracellular acidification and the effect of
      bicarbonate on cerivastatin-induced apoptosis using an RD cell line as a model of
      in vitro skeletal muscle. Cerivastatin reduced the number of viable cells and
      caused dramatic morphological changes and DNA fragmentation in a concentration
      dependent manner. Moreover, cerivastatin-induced apoptosis was associated with
      intracellular acidification and caspase-9 and -3/7 activation. On the other hand,
      bicarbonate suppressed cerivastatin-induced pH alteration, caspase activation,
      morphological change and reduction of cell viability. Accordingly, bicarbonate
      suppressed statin-induced apoptosis. The strategy to combine statins with
      bicarbonate can lead to reduction in the chance of the severe adverse events
      including myopathy or rhabdmyolysis.

PMID- 17553642
TI  - The molecular conformation of Ibuprofen, C13H18O2, through X-ray diffuse
      scattering.
AB  - A study of the three-dimensional distribution of the X-ray diffuse scattering
      from the pharmaceutical Ibuprofen (2-(4-isobutylphenyl)propionic acid,
      C(13)H(18)O(2)) has been undertaken. The most important aspects of the molecular
      flexibility have been isolated, as have key correlations between variables within
      a single molecule. Hence, aspects of the conformational space of the molecule
      within a crystalline environment have been outlined. For example the correlations
      between torsional twists on different bonds in the molecule (corresponding to the
      torsional angles on atoms C3, O1 and C11) have been established. Even though the
      atoms are on opposite sides of the phenyl group, there is a strong negative
      correlation between the torsional angle on C3 and that on C11. This shows that
      the ability to predict the conformation a fragment of a molecule will adopt based
      on the conformations of the fragment found in other molecules may be limited, as
      aspects of molecular geometry far from the fragment itself will have impact on
      its conformation. Between molecules, the positional coordinate components which
      coincide with the direction of propagation of strong intermolecular contacts,
      particularly the -COOH-HOOC- dimerising interactions, are positively correlated.
      On the other hand, motions perpendicular to such directions, and rotations about
      the torsional angles, do not propagate strongly from molecule to molecule.

PMID- 17553643
TI  - Analysis of ketamine and norketamine in urine by automatic solid-phase extraction
      (SPE) and positive ion chemical ionization-gas chromatography-mass spectrometry
      (PCI-GC-MS).
AB  - Ketamine (KT) is widely abused for hallucination and also misused as a "date
      rape" drug in recent years. An analytical method using positive ion chemical
      ionization-gas chromatography-mass spectrometry (PCI-GC-MS) with an automatic
      solid-phase extraction (SPE) apparatus was studied for the determination of KT
      and its major metabolite, norketamine (NK), in urine. Six ketamine suspected
      urine samples were provided by the police. For the research of KT metabolism, KT
      was administered to SD rats by i.p. at a single dose of 5, 10 and 20mg/kg,
      respectively, and urine samples were collected 24, 48 and 72 h after
      administration. For the detection of KT and NK, urine samples were extracted on
      an automatic SPE apparatus (RapidTrace, Zymark) with mixed mode type cartridge,
      Drug-Clean (200 mg, Alltech). The identification of KT and NK was by PCI-GC-MS.
      m/z238 (M+1), 220 for KT, m/z 224 (M+1), 207 for NK and m/z307 (M+1) for Cocaine
      D(3) as internal standard were extracted from the full-scan mass spectrum and the
      underlined ions were used for quantitation. Extracted calibration curves were
      linear from 50 to 1000 ng/mL for KT and NK with correlation coefficients
      exceeding 0.99. The limit of detection (LOD) was 25 ng/mL for KT and NK. The
      limit of quantitation (LOQ) was 50 ng/mL for KT and NK. The recoveries of KT and
      NK at three different concentrations (86, 430 and 860 ng/mL) were 53.1 to 79.7%
      and 45.7 to 83.0%, respectively. The intra- and inter-day run precisions (CV) for
      KT and NK were less than 15.0%, and the accuracies (bias) for KT and NK were also
      less than 15% at the three different concentration levels (86, 430 and 860
      ng/mL). The analytical method was also applied to real six KT suspected urine
      specimens and KT administered rat urines, and the concentrations of KT and NK
      were determined. Dehydronorketamine (DHNK) was also confirmed in these urine
      samples, however the concentration of DHNK was not calculated. SPE is simple, and
      needs less organic solvent than liquid-liquid extraction (LLE), and PCI-GC-MS can
      offer both qualitative and quantitative information for urinalysis of KT in
      forensic analysis.

PMID- 17553644
TI  - Interleukin-6 attenuates hyperthermia-induced seizures in developing rats.
AB  - Previous studies indicated that several cytokines influenced the seizure
      propensity in convulsive disorders and were the cause of encephalopathies in
      childhood. We studied the role of one inflammatory cytokine, interleukin-6 (IL
      6), in hyperthermia-induced seizures in developing rats. Twenty-four male Lewis
      rats (23-28 days old) were divided into three groups (n=8/IL-6 (500 ng), IL-6 (50
      ng), and saline control groups). We applied human recombinant IL-6 intra-nasally
      to developing rats 1h before seizures induced by moist heated air (50 degrees C).
      The seizure latency was defined as the time from hyperthermia onset until the
      appearance of continuous seizure discharges on electroencephalography (EEG), and
      the seizure duration as the duration of continuous spike and wave discharges on
      EEG. Five of the eight rats in the IL-6 (500 ng) group, two in the IL-6 (50 ng)
      group, and one in the control group exhibited no seizure discharges during the
      360 s heating period. In these cases, the seizure latency time was regarded as
      360 s and the seizure duration time as 0 s. The median seizure latency for the IL
      6 (500 ng) group, 360 s (range: 256-360), was significantly longer than that for
      the control one, 249 (121-360) (P<0.05). The seizure duration for the IL-6 (500
      ng) group, 0 s (0-20), was significantly shorter than that for the control one,
      33 (0-76) (P<0.025). Also, the adenosine receptor antagonist, aminophylline,
      prevented these effects of IL-6 on hyperthermia-induced seizures. These results
      indicate that IL-6 plays an anti-convulsive role through the adenosine system in
      hyperthermia-induced seizures, which might be relevant as to human febrile
      seizures.

PMID- 17553645
TI  - Radiologic findings in taxane induced colitis.
AB  - Ischemic colitis in breast cancer patients being treated with taxane-based
      chemotherapy, which may lead to serious morbidities and even death, has recently
      been defined as a clinical entity. The purpose of this retrospective study was to
      evaluate the computed tomography (CT) findings in taxane-related colitis and
      determine their clinical relevance. CT scans of 41 patients at risk for taxane
      colitis were reviewed retrospectively for bowel and peritoneal abnormalities.
      Morphological findings were analyzed and correlated with clinical, pathological,
      and endoscopic findings. CT scans in 10 of the 41 patients showed a definitely
      abnormal colon with a thickened wall or distended with fluid, signs that are
      suggestive of colitis, in the context of the clinical picture. Radiographic
      changes in patients with taxane colitis are not specific but, in the appropriate
      context, can suggest the correct diagnosis and guide the patient's management.

PMID- 17553646
TI  - Whole-brain voxel-based morphometry of white matter in medial temporal lobe
      epilepsy.
AB  - PURPOSE: The purpose of this study was to analyze whole-brain white matter
      changes in medial temporal lobe epilepsy (MTLE). MATERIALS AND METHODS: We
      studied 23 patients with MTLE and 13 age- and sex-matched healthy control
      subjects using voxel-based morphometry (VBM) on T1-weighted 3D datasets. The
      seizure focus was right sided in 11 patients and left sided in 12. The data were
      collected on a 1.5 T MR system and analyzed by SPM 99 to generate white matter
      density maps. RESULTS: Voxel-based morphometry revealed diffusively reduced white
      matter in MTLE prominently including bilateral frontal lobes, bilateral temporal
      lobes and corpus callosum. White matter reduction was also found in the bilateral
      cerebellar hemispheres in the left MTLE group. CONCLUSION: VBM is a simple and
      automated approach that is able to identify diffuse whole-brain white matter
      reduction in MTLE.

PMID- 17553647
TI  - Degradation of high-molar-mass hyaluronan by an oxidative system comprising
      ascorbate, Cu(II), and hydrogen peroxide: inhibitory action of antiinflammatory
      drugs--naproxen and acetylsalicylic acid.
AB  - Changes in dynamic viscosity of the solutions of a high-molar-mass hyaluronan
      (HA) were monitored using a rotational viscometer. The degradative conditions
      generated in the HA solutions by a system comprising ascorbate plus Cu(II) plus
      H(2)O(2) were studied either in the presence or absence of a drug--naproxen or
      acetylsalicylic acid. Continual decrease of the dynamic viscosity of HA solution
      was indicative of the polymer degradation. Addition of the drug
      retarded/inhibited the HA degradation in a concentration-dependent manner. The
      characteristics of the fragmented polymers were investigated by FT-IR
      spectroscopy and by two different liquid chromatographic techniques, namely by
      size-exclusion chromatography equipped with a multi-angle light scattering
      photometric detector and by high-performance liquid chromatography connected on
      line to a spectrofluorometer.

PMID- 17553648
TI  - Validation and application of a liquid chromatographic-mass spectrometric method
      for determination of artesunate in pharmaceutical samples.
AB  - A simple and rapid liquid chromatographic-mass spectrometric assay for the
      evaluation of artesunate in vials for injection has been developed and validated.
      The content of each vial was dissolved in 3.0 mL of methanol using a SGE
      analytical syringe (1.0 mL). Each sample was diluted to a theoretical
      concentration of 1000 ng/mL and analysed in triplicate. Three replicates of
      calibration standards at concentrations 500, 1000 and 1500 ng/mL were used to
      construct a calibration curve. Artesunate was analysed by liquid chromatography
      with atmospheric pressure chemical ionisation (APCI) mass spectrometric (MS)
      detection on a Hypersil Gold column (100 mm x 4.6 mm) using a mobile phase
      containing methanol-ammonium acetate 10 mM pH 5.3 (70:30, v/v) at a flow rate of
      1 mL/min. The assay was implemented for the analysis of artesunate for injection
      purchased from Guilin Pharmaceutical Company in China.

PMID- 17553649
TI  - New method for high-performance liquid chromatographic determination of
      amantadine and its analogues in rat plasma.
AB  - A novel precolumn derivatization method is described for the quantitative
      determination of amantadine, rimantadine and memantine in biological samples by
      HPLC with UV detection. The derivatization was performed at room temperature
      using anthraquinone-2-sulfonyl chloride (ASC) as reagent for only 10 min and
      without postderivatization treatment to inactivate excess reagent. The
      derivatives were analyzed by isocratic HPLC with a UV detector at 256 nm on a
      Lichrosper C18 column. The linear range for the determination of three drugs
      spiked in plasma (0.2 ml) was 0.05-5.0 microg/ml for amantadine and rimantadine,
      0.05-2.0 microg/ml for memantine, respectively. The limits of detection and
      quantification were 20 and 50 ng/ml for the analytes, respectively. Application
      of the method to the analysis of amantadine, rimantadine and memantine in rat
      plasma and pharmacokinetic studies are demonstrated and proved feasible.

PMID- 17553650
TI  - The use of mixed-mode ion-exchange solid phase extraction to characterize
      pharmaceutical drug degradation.
AB  - Solid phase extraction (SPE) has been utilized extensively in the pharmaceutical
      industry for the isolation of pharmaceuticals from interfering biological
      matrices and the purification and concentration of impurities and degradation
      products present in analytical samples. The work described herein involves the
      novel use of mixed-mode ion-exchange solid phase extraction to characterize
      degradation products of several pharmaceutical drugs, thereby giving important
      clues to their structure and sites of reactivity. Several examples of the use of
      mixed-mode ion-exchange solid phase extraction to illustrate the utility of this
      technique are presented.

PMID- 17553651
TI  - Advances in development of transgenic plants for remediation of xenobiotic
      pollutants.
AB  - Phytoremediation-the use of plants for cleaning up of xenobiotic compounds-has
      received much attention in the last few years and development of transgenic
      plants tailored for remediation will further enhance their potential. Although
      plants have the inherent ability to detoxify some xenobiotic pollutants, they
      generally lack the catabolic pathway for complete degradation/mineralization of
      these compounds compared to microorganisms. Hence, transfer of genes involved in
      xenobiotic degradation from microbes/other eukaryotes to plants will further
      enhance their potential for remediation of these dangerous groups of compounds.
      Transgenic plants with enhanced potential for detoxification of xenobiotics such
      as trichloro ethylene, pentachlorophenol, trinitro toluene, glycerol trinitrate,
      atrazine, ethylene dibromide, metolachlor and hexahydro-1,3,5-trinitro-1,3,5
      triazine are a few successful examples of utilization of transgenic technology.
      As more genes involved in xenobiotic metabolism in microorganisms/eukaryotes are
      discovered, it will lead to development of novel transgenic plants with improved
      potential for degradation of recalcitrant contaminants. Selection of suitable
      candidate plants, field testing and risk assessment are important considerations
      to be taken into account while developing transgenic plants for phytoremediation
      of this group of pollutants. Taking advantage of the advances in biotechnology
      and 'omic' technologies, development of novel transgenic plants for efficient
      phytoremediation of xenobiotic pollutants, field testing and commercialization
      will soon become a reality.

PMID- 17553652
TI  - Communication during ward rounds in internal medicine. An analysis of patient
      nurse-physician interactions using RIAS.
AB  - OBJECTIVE: Describe the content and of mode of patient-physician-nurse
      interactions during ward-rounds in Internal Medicine. METHODS: In 267/448
      patients, 13 nurses, and 8 physicians from two wards in General Internal Medicine
      448 interactions on ward rounds were tape recorded by observers. After exclusion
      of interactions with more than three participants (N=150), a random sample of 90
      interactions was drawn. Data were analysed with a modified RIAS version that
      allowed for the registration of a third contributor and for the assessment of the
      direction of a communicative action (e.g.: nurse-->patient, etc.). Furthermore,
      time spent per individual patient was registered with a stop-watch. RESULTS: A
      total of 12,078 utterances (144 per ward round) were recorded. Due to problems
      with the comprehensibility of some interactions the final data set contains 71
      ward round interactions with 10,713 utterances (151 per ward round interaction).
      The average time allotted to an individual patient during ward-rounds was 7.5 min
      (range: 3-16 min). The exchange of medical information is the main topic in
      physicians (39%) and nurses (25%), second common topic in patients (28%), in whom
      communicative actions like agreement or checking are more common (30%
      patients/25% physicians/22% nurses). Physicians and patients use a substantial
      number of communicative actions (1397/5531 physicians; 1119/3733 patients).
      Patients receive about 20 bits of medical or therapeutic information per contact
      during ward-rounds. CONCLUSIONS: If ward rounds serve as the central marketplace
      of information nurses' knowledge is under-represented. Further research should
      try to determine whether the quality of patient care is related to a well
      balanced exchange of information, to which nurses, physicians, and patients
      contribute their specific knowledge. PRACTICE IMPLICATIONS: Given the fact that
      in-patients in Interna Medicine usually present complex problems, the exchange of
      factual information, expectations, and concepts is of paramount importance. We
      hope that this paper is going to direct the attention of the scientific community
      to the characteristics of ward-rounds because they will remain the central
      marketplace of communication in hospital.

PMID- 17553653
TI  - Cyclooxygenase-2 expression is related to prognosis in patients with esophageal
      squamous cell carcinoma.
AB  - AIM: Esophageal carcinoma is one of the most aggressive malignancies. Many
      studies have examined various biological factors associated with the malignant
      potential of esophageal carcinoma. Cyclooxygenase (COX)-2 is overexpressed in
      various types of human malignancies, including esophageal carcinomas. Although
      some groups have described COX-2 expression in esophageal adenocarcinoma, few
      studies have reported COX-2 expression in esophageal squamous cell carcinoma
      (ESCC). METHODS: We immunohistochemically investigated relationships between COX
      2 overexpression in surgical specimens of primary tumors in 228 patients with
      ESCC. Relationships between COX-2 expression and clinicopathological factors,
      including prognosis, were analyzed. COX-2 expressions were classified into 4
      criteria: Score 0, no staining; Score 1, <10% staining; Score 2, 10-90% staining;
      and Score 3, >90% staining. RESULTS: Scores of COX-2 immunoreactivity in 228
      patients were as follows: Score 0, 21 of 228; Score 1, 71of 228; Score 2, 117 of
      228; and Score 3, 19 of 228, respectively. COX-2 expression was significantly
      correlated with depth of invasion and tumor stage (p=0.03 and p=0.04,
      respectively). The 5-year survival rate of patients decreased significantly with
      increased expression of COX-2 (p=0.005). Multivariate regression analysis
      indicated COX-2 expression as an independent prognostic factor for ESCC.
      CONCLUSIONS: COX-2 overexpression was significantly correlated with depth of
      invasion, tumor stage and survival in ESCC. Evaluation of COX-2 expression should
      be useful for determining tumor properties, including prognosis, in patients with
      ESCC.

PMID- 17553654
TI  - Age influences TSH serum levels after withdrawal of l-thyroxine or rhTSH
      stimulation in patients affected by differentiated thyroid cancer.
AB  - Recombinant human TSH (rhTSH) has been recently suggested for radioiodine
      ablation in patients with differentiated thyroid cancer (DTC). To date, studies
      are still not available about the effectiveness of rhTSH stimulation depending on
      the age, since serum TSH clearance may be different in younger and in older
      patients. The aim of this study was to investigate the influence of age to serum
      TSH levels after rhTSH stimulation and thyroid hormone withdrawal (THW). We
      retrospectively evaluated two groups of consecutive DTC patients: group 1 (311
      patients, age 49.0+/-13.6 years, ranging 15-86) underwent rhTSH stimulation 6-12
      months after thyroid ablation (rhTSH-group); group 2 (84 patients, age 46.9+/
      13.5 years, ranging 20-77) was followed by THW (THW-group). The influence of age,
      gender, body mass index and body surface area to serum TSH levels were evaluated
      in both groups. RhTSH-group: on day 5 (d5), TSH levels were 32.7+/-21.4 microU/ml
      (range 0.8-136.6). By univariate analysis, d5-TSH was positively related to age
      (r=0.27, p=0.0001) and no correlations were found with the other parameters. At
      multivariate analysis, both age and gender (female) were independently associated
      with d5-TSH levels. THW-group: after thyroid hormone withdrawal, TSH levels were
      71.1+/-36.4 microU/ml (range 8.5-200). At univariate analysis, only age was
      significantly and negatively related to serum TSH levels (r=-0.31, p=0.004). Our
      data indicate that age and gender seem to positively influence serum TSH levels
      after rhTSH stimulation. An opposite effect of age on serum TSH levels has been
      observed after THW. Therapeutic implications ((131)I-treatment) of these findings
      have to be better investigated in prospective studies.

PMID- 17553655
TI  - [Vascular dementia and mixed dementia].
AB  - The concept of vascular dementia has evolved over the past century to include
      multiple underlying pathophysiological mechanisms. Neuroimaging techniques offer
      new and better ways to identify the presence of cerebrovascular pathology,
      although they do not improve our ability to link these changes to the onset of
      clinical cognitive impairment. Clinical criteria for vascular dementia have also
      evolved but they remain imperfect. Most epidemiological studies define mixed
      dementia as the coexistence of Alzheimer's disease and vascular dementia.
      Clinicopathologic correlations show a clear association between the concomitant
      presence of vascular and Alzheimer lesions and the severity of cognitive
      impairment in mixed dementia and provide strong support for the validity of the
      mixed dementia concept. Mixed dementia is a very frequent disease that remains
      underdiagnosed, especially in the elderly. The diagnosis of vascular and mixed
      dementia remains a clinical challenge and cannot be improved without further
      studies of clinicopathological correlations and functional neuroimaging.
      Preventive therapeutic interventions include control of vascular risk factors and
      especially treatment of hypertension.

PMID- 17553656
TI  - [Management of hemochromatosis linked to HFE gene].
AB  - Phenotypic expression of the homozygous C282Y/C282Y mutation of the HFE gene has
      been classified in five stages, and appropriate management recommended for each
      stage. Phlebotomy is indicated for stages>or=2, that is, with elevated
      transferrin saturation and serum ferritin levels >300 microg/L in men and >200
      microg/L in women. Maximal volume per phlebotomy is 7 mL/kg and should not exceed
      550 mL. The main goal of this iron-depletion therapy is to reach and maintain
      serum ferritin levels<or=50 microg/L. Phlebotomies performed at home by nurses
      should be encouraged, under strict conditions. Because genetic counseling and
      family screening should follow individual diagnosis, the physician must recommend
      that the patient inform siblings, adult children, and parents. Screening should
      include simultaneous genetic testing and serum iron markers.

PMID- 17553657
TI  - [Unusual cause of hypogastric mass in men].

PMID- 17553658
TI  - [Duodenal leiomyosarcoma revealed by gastrointestinal hemorrhage].
AB  - INTRODUCTION: Leiomyosarcomas account for approximately 75% of all
      gastrointestinal sarcomas but only 8-10% of duodenal malignancies. Pain and
      bleeding are the principal symptoms. Prognosis of these tumors is difficult to
      assess. If excision is successful, however, prognosis is usually good. We report
      the case of a patient with leiomyosarcoma of the duodenum first identified
      because of gastrointestinal hemorrhage. CASE: We report the case of a 57-year-old
      women who underwent duodenopancreatectomy for duodenal leiomyosarcoma.
      Histological and immunohistochemical findings confirmed the diagnosis of low
      grade leiomyosarcoma and ruled out a gastrointestinal stromal tumor. DISCUSSION:
      Duodenal leiomyosarcomas are very rare. Preoperative diagnosis is difficult. The
      combination of a mass and a hemorrhage must suggest the presence of
      leiomyosarcoma. Radiological and endoscopic findings may not be conclusive: only
      histologic examination provided the definitive diagnosis here. Many criteria have
      been used to assess prognosis; complete resection appears to be the principal
      prognostic factor and is associated with improved survival.

PMID- 17553659
TI  - Breakthrough pain in children with cancer.
AB  - The aims of this prospective study were to determine the prevalence,
      characteristics, and impact of breakthrough pain in children with cancer. Twenty
      seven pediatric inpatients with cancer (aged 7-18 years) who had severe pain
      requiring treatment with opioids and who received care in the Oncology Unit at
      the Children's Hospital at Westmead, Sydney, Australia participated in this
      study. The children responded to a structured interview (Breakthrough Pain
      Questionnaire for Children), designed to characterize breakthrough pain in
      children. Measures of pain, anxiety, and depressed mood were completed. Fifty
      seven percent of the children experienced one or more episodes of breakthrough
      pain during the preceding 24 hours, each episode lasting seconds to minutes,
      occurring 3-4 times/d, and most commonly characterized as "sharp" and "shooting"
      by the children. Younger children (7-12 years) had a significantly higher risk of
      experiencing breakthrough pain compared to teenagers. No statistical difference
      could be shown between children with and without breakthrough pain in regard to
      anxiety and depression. The most effective treatment of an episode of
      breakthrough pain was a patient-controlled analgesia opioid bolus dose. Further
      studies of breakthrough pain in children and more effective treatment strategies
      in this age group are necessary.

PMID- 17553660
TI  - Reduced tubulin tyrosination as an early marker of mercury toxicity in
      differentiating N2a cells.
AB  - The aims of this work were to compare the effects of methyl mercury chloride and
      thimerosal on neurite/process outgrowth and microtubule proteins in
      differentiating mouse N2a neuroblastoma and rat C6 glioma cells. Exposure for 4h
      to sublethal concentrations of both compounds inhibited neurite outgrowth to a
      similar extent in both cells lines compared to controls. In the case of N2a
      cells, this inhibitory effect by both compounds was associated with a fall in the
      reactivity of western blots of cell extracts with monoclonal antibody T1A2, which
      recognises C-terminally tyrosinated alpha-tubulin. By contrast, reactivity with
      monoclonal antibody B512 (which recognises total alpha-tubulin) was unaffected at
      the same time point. These findings suggest that decreased tubulin tyrosination
      represents a neuron-specific early marker of mercury toxicity associated with
      impaired neurite outgrowth.

PMID- 17553661
TI  - Transfection of HepG2 cells with hGSTA4 provides protection against 4
      hydroxynonenal-mediated oxidative injury.
AB  - 4-Hydroxynonenal (4-HNE) is a mutagenic alpha,beta-unsaturated aldehyde produced
      during oxidative injury that is conjugated by several glutathione S-transferase
      (GST) isoforms. The alpha class human GSTA4-4 enzyme (hGSTA4-4) has a
      particularly high catalytic efficiency toward 4-HNE conjugation. However, hGST4-4
      expression is low in most human cells and there are other aldehyde metabolizing
      enzymes that detoxify 4-HNE. In the current study, we determined the effect of
      over-expression of hGSTA4 mRNA on the sensitivity of HepG2 cells to 4-HNE injury.
      HepG2 cells transfected with an hGSTA4 vector construct exhibited high steady
      state hGSTA4 mRNA, high GST-4-HNE catalytic activities, but lower basal
      glutathione (GSH) concentrations relative to insert-free vector (control) cells.
      Exposure to 4-HNE elicited an increase in GSH concentrations in the control and
      hGSTA4 cells, although the dose-response of GSH induction differed among the two
      cell types. Specifically, hGSTA4 cells had significantly higher GSH
      concentrations when exposed to 5-15 microM 4-HNE, but not at 20 microM 4-HNE,
      suggesting extensive GSH utilization at high concentrations of 4-HNE. The hGSTA4
      cells exhibited a significant growth advantage relative to control cells in the
      absence of 4-HNE, and a trend towards increased growth at low dose exposures to 4
      HNE. However, the hGSTA4 cells did not exhibit a growth advantage relative to
      control cells at higher 4-HNE exposures associated with increased GSH
      utilization. As expected, the hGSTA4 cells showed resistance to 4-HNE stimulated
      lipid peroxidation at all 4-HNE doses. In summary, our data indicates that over
      expression of hGSTA4 at levels conferring high GST-4-HNE conjugating activity
      confers a partial growth advantage to HepG2 cells and protects against 4-HNE
      oxidative injury. However, the loss of proliferative capacity of hGSTA4 cells
      challenged with levels of 4-HNE associated with severe oxidative stress indicates
      a role of other aldehyde metabolizing enzymes, and/or GSH-electrophile
      transporter proteins, in providing full cellular protection against 4-HNE
      toxicity.

PMID- 17553662
TI  - Arsenic metabolites affect expression of the neurofilament and tau genes: an in
      vitro study into the mechanism of arsenic neurotoxicity.
AB  - Neurological studies indicate that the central (CNS) and peripheral nervous
      system (PNS) may be affected by arsenic (As). As-exposed patients show
      significantly lower nerve conduction velocities (NCVs) in their peripheral nerves
      in comparison to healthy subjects. As may play a role in the disruption of
      neuroskeletal integrity, but the mechanisms by which it exerts a toxic effect on
      the peripheral and central nervous system are still unclear. In the present
      study, we examined the neurotoxic effects of various arsenic metabolites
      (iAs(III), iAs(V), MMA(V) and DMA(V)) on two different cell lines derived from
      the peripheral (ST-8814) and central (SK-N-SH) nervous system. The effects of the
      arsenic metabolites were examined on the relative quantification levels of the
      cytoskeletal genes, neurofilament-light (NEFL), neurofilament-medium (NEF3),
      neurofilament-heavy (NEFH) and microtubule-associated protein-tau (MAPT), using
      real-time PCR. Our results show that iAs(III) and iAs(V) have no significant
      effects on either cell lines. On the other hand, MMA(V) and DMA(V) cause
      significant changes in expression levels of NEF3 and NEFL genes, while the
      expression level of the NEFH gene is significantly increased in both cell lines.

PMID- 17553664
TI  - Heterogeneous medically unexplained symptoms and immune function.
AB  - It has been suggested that dysregulation of immune-to-brain communication plays a
      role in the biopsychological process underlying medically unexplained symptoms
      (MUS). Immune and non-immune stressors can both be involved in the activation of
      the central sickness-behavioural-system leading to complaints like malaise, pain
      and fatigue. We hypothesized increased pro-inflammatory and/or reduced anti
      inflammatory cytokine activity to exist in MUS patients. Twenty-seven
      participants (4 male; 23 female) with heterogeneous MUS were compared with 27
      healthy controls (6 male; 21 females). Blood samples were analysed for leukocyte
      subset cell counts, in vitro T-cell mitogen-stimulated cytokine production (IL-2,
      IL-4, IL-5, IL-6, IL-10, TNF-alpha and IFN-gamma) and in vitro monocyte cytokine
      release (IL-1beta, IL-6, IL-8, IL-10 and TNF-alpha) in response to increasing
      concentrations of LPS. No significant group differences were found for any of the
      cytokines measured. One unexpected exception was an elevation in the number of
      circulating B and NK-cells in participants high on MUS. Nonetheless, no support
      was found for the hypothesized immunological dysregulation in peripheral blood
      leukocyte function of MUS patients.

PMID- 17553663
TI  - Genome-wide transcriptome profiling of region-specific vulnerability to oxidative
      stress in the hippocampus.
AB  - Neurons in the hippocampal CA1 region are particularly sensitive to oxidative
      stress (OS), whereas those in CA3 are resistant. To uncover mechanisms for
      selective CA1 vulnerability to OS, we treated organotypic hippocampal slices with
      duroquinone and compared transcriptional profiles of CA1 vs CA3 cells at various
      intervals. Gene Ontology and Biological Pathway analyses of differentially
      expressed genes showed that at all time points, CA1 had higher transcriptional
      activity for stress/inflammatory response, transition metal transport,
      ferroxidase, and presynaptic signaling activity, while CA3 had higher GABA
      signaling, postsynaptic, and calcium and potassium channel activity. Real-time
      PCR and immunoblots confirmed the transcriptome data and the induction of OS by
      duroquinone in both hippocampal regions. Our functional genomics approach has
      identified in CA1 cells molecular pathways as well as unique genes, such as
      guanosine deaminase, lipocalin 2, synaptotagmin 4, and latrophilin 2, whose time
      dependent induction following the initiation of OS may represent attempts at
      neurite outgrowth, synaptic recovery, and resistance against OS.

PMID- 17553665
TI  - Detection of an unstable non-coding tandem repeat in the ZNF291 gene.
AB  - Repeat instability is an important form of mutation that is responsible for
      several neurological, neurodegenerative and neuromuscular disorders. In this
      study we identified an unstable [CCTG](n) repeat in the second intron of the
      ZNF291 gene, on chromosome 15q21-24. The repeat number is polymorphic in normal
      population and the ZNF291 transcript is expressed in different areas of human
      brain, skeletal muscle and heart. These findings suggest that ZNF291 gene should
      be taken in consideration as an attractive candidate for neuromuscular expansion
      related diseases mapping in this locus.

PMID- 17553666
TI  - Conjugated polythiophene probes target lysosome-related acidic vacuoles in
      cultured primary cells.
AB  - Conformation-sensitive optical probes for studying biological processes and
      structures are of great interest. The present work shows for the first time that
      conjugated polyelectrolyte (CPE) probes can be used for specific targeting of
      chromatin, nuclear and cytoplasmatic vesicles, and cytoskeletal components in a
      complex system of cultured cells. One of the probes could also be used for vital
      staining of live cells. When bound to different entities, the polythiophene
      derivative probes emitted light with different colors due to the unique spectral
      properties of these conformation sensitive probes. The physical pre-requisites
      for binding could also be exploited for characterization of the target.
      Unexpectedly, lysosome-related acidic vacuoles were targeted in cultured primary
      cells by both anionic, cationic, and zwitter-ionic polythiophene derivatives. Pre
      treatment with Bafilomycin A1, a specific inhibitor of vacuolar-type H(+)-ATPase,
      caused redistribution of the staining. The targeting of lysosome-related acidic
      vesicles could not be demonstrated in transformed cells (melanoma, neuroblastoma,
      and prostate cancer cell lines), indicating a difference in the localization,
      structure, accessibility, or quantity of the target in cultured normal cells as
      compared with the malignant cell lines. The chemical nature of the conjugated
      polyelectrolyte complex in the cytoplasmatic vacuoles remains elusive.

PMID- 17553667
TI  - Blood lead levels and specific attention effects in young children.
AB  - The detrimental effects of early exposure to lead are credible and persistent,
      but there is presently no agreement on a safe threshold for circulating lead
      levels. Although several research groups have found significantly poorer
      cognitive performance in children who have whole blood levels as low as 5
      microg/dL, most government agencies, including the EPA and the CDC, continue to
      use 10 microg/dL as the criterion for concern in public health advisories. Prior
      research has consistently indicated a negative relation between lead levels and
      attention. Similarly, the results of the present study show a relation between
      blood lead level and neurobehavioral outcome in 7-year-old children (N=506).
      Higher lead levels were associated significantly with decreased scores on
      measures of intelligence (i.e., overall, performance and verbal IQ), lengthened
      reaction time, hyperactivity, and social and delinquent behavior problems.
      Importantly, the present study documents a significant negative impact of blood
      lead levels on attention, but not impulsivity, in early elementary age children,
      further delineating the specific aspects of attention related to blood lead
      concentrations. Analyses were also conducted to identify a "safe" blood lead
      level threshold. Visual inspection of non-parametric regression plots suggested a
      gradual linear dose-response relationship for each endpoint. None of the
      neurobehavioral outcomes assessed showed evidence of a threshold under which lead
      levels appear to "safe". In light of the consistency of these findings with those
      of several other groups, it is advisable to consider whether the threshold for an
      acceptable blood lead level should be reduced.

PMID- 17553669
TI  - Influence of levetiracetam on the anticonvulsant efficacy of conventional
      antiepileptic drugs against audiogenic seizures in DBA/2 mice.
AB  - Levetiracetam (LEV, [S]-alpha-ethyl-2-oxo-1-pyrrolidine acetamide) is a new
      antiepileptic that has been used as adjunctive therapy to treat patients with
      intractable epilepsy. Systemic administration of levetiracetam (2.5-30 mg/kg,
      intraperitoneally (i.p.)) was able to produce a dose-dependent decrease in DBA/2
      audiogenic seizure severity score. In combination with conventional antiepileptic
      drugs, levetiracetam, 5mg/kg, i.p., which per se did not significantly affect the
      occurrence of audiogenic seizures in DBA/2 mice, potentiated the anticonvulsant
      activity of some antiepileptic drugs studied against sound-induced seizures in
      DBA/2 mice. The degree of potentiation induced by levetiracetam was greater,
      approximately twice, for carbamazepine, diazepam, felbamate, topiramate,
      gabapentin, and valproate, less for lamotrigine, phenobarbital and phenytoin.
      This increase was associated with a comparable impairment in motor activity;
      however, the therapeutic index of combined treatment of antiepileptic drugs with
      levetiracetam was more favourable than the combination with saline with the
      exception of lamotrigine, phenytoin and phenobarbital. Since levetiracetam did
      not significantly influence the total and free plasma and the brain levels of
      antiepileptics studied. In addition, levetiracetam did not significantly affect
      the hypothermic effects of the anticonvulsants tested. In conclusion,
      levetiracetam showed an additive anticonvulsant effect when administered in
      combination with some classical anticonvulsants, most notably carbamazepine,
      diazepam, felbamate, gabapentin, topiramate and valproate, implicating a possible
      therapeutic relevance of such drug combinations.

PMID- 17553670
TI  - Efficacy and safety of adjunctive zonisamide therapy for refractory partial
      seizures.
AB  - An approach to the selection of appropriate antiepileptic drugs (AEDs) for
      inclusion in polytherapy is to take into account both the efficacy of a drug and
      also its mechanism of action and pharmacokinetic profile. The AED zonisamide is
      licensed in Europe and the USA for use as adjunctive therapy in adult patients
      with partial onset epilepsy. Four pivotal clinical studies in patients with
      refractory partial seizures demonstrated that zonisamide as an add-on was most
      effective at doses of >or=300 mg/day, with responder rates (>or=50% reduction
      from baseline in seizure frequency) ranging from 28 to 47% for all seizures. In
      addition, zonisamide has a unique combination of multiple mechanisms of action
      that are potentially complementary with concomitant AEDs. Zonisamide has no
      clinically relevant effects on the pharmacokinetics of other commonly used AEDs,
      however, co-administration with cytochrome P450 3A4 (CYP3A4) inducers or
      inhibitors may change zonisamide's pharmacokinetic profile. Zonisamide is well
      tolerated with the majority of adverse events being mild-to-moderate and
      generally manageable. The tolerability of zonisamide has also been shown to
      improve with slower drug titration and duration of drug treatment. These
      characteristics suggest that zonisamide may be suitable as a key adjunct in
      rational polytherapy.

PMID- 17553671
TI  - Sodium valproate versus lamotrigine: a randomised comparison of efficacy,
      tolerability and effects on circulating androgenic hormones in newly diagnosed
      epilepsy.
AB  - We have performed a randomised, prospective study to compare the efficacy and
      tolerability of sodium valproate (VPA) and lamotrigine (LTG) monotherapy, and
      their effects on circulating androgenic hormones, in newly diagnosed epilepsy. A
      total of 225 patients (116 male; median age 35 years, range 13-80 years) were
      followed-up at 6-weekly intervals until they reached an end-point (12 months'
      seizure freedom; withdrawal due to intolerable side-effects; lack of efficacy
      despite adequate dosing). Twelve month seizure-free rates were identical (47%) in
      the VPA (n=111) and LTG (n=114) treatment arms. More patients taking VPA withdrew
      from the study due to adverse events (26 VPA versus 15 LTG; p=0.046). Eight
      patients, all taking VPA, dropped out during the first 6 months due to weight
      gain. There were no changes in mean serum concentrations of testosterone, sex
      hormone binding globulin and androstenedione or in the free androgen index after
      6 or 12 months' treatment with either drug in 112 patients who fulfilled the
      criteria for hormone analysis. No difference in efficacy was found between VPA
      and LTG in our patients with newly diagnosed epilepsy. LTG appeared to be better
      tolerated. Neither drug appeared to alter the circulating levels of androgenic
      hormones.

PMID- 17553668
TI  - Scaffold mediated regulation of MAPK signaling and cytoskeletal dynamics: a
      perspective.
AB  - Cell migration is critical for many physiological processes and is often
      misregulated in developmental disorders and pathological conditions including
      cancer and neurodegeneration. MAPK signaling and the Rho family of proteins are
      known regulators of cell migration that exert their influence on cellular
      cytoskeleton during cell adhesion and migration. Here we review data supporting
      the view that localized ERK signaling mediated through recently identified
      scaffold proteins may regulate cell migration.

PMID- 17553672
TI  - Intra-amygdala all-trans retinoic acid inhibits amygdala-kindled seizures in
      rats.
AB  - Amygdala plays an important role in induction and control of limbic seizures.
      There is a network of gap junctional communications in basolateral amygdala (BLA)
      as well. We compared the effect of intra-BLA infusion of the typical gap junction
      (GJ) blocker carbenoxolone (CBX), with the effect of putative GJ blocker all
      trans retinoic acid (ATRA), on the afterdischarge (AD) recorded from BLA in
      amygdala-kindled rats. Both CBX and ATRA showed a rapid anti-seizure effect.
      Conversely, intra-BLA infusion of the known GJ opener, trimethylamine (TMA),
      enhanced seizure susceptibility by prolonging the duration of AD and generalized
      behavioral seizures. ATRA administered intra-BLA prevented the proconvulsant
      effect of TMA. The reduction of gap junctional conductance might be involved in
      the observed anticonvulsant effect of ATRA.

PMID- 17553673
TI  - A preliminary study of emotion processing interference in schizophrenia and
      schizoaffective disorder.
AB  - The impact of emotional arousal may be an equal or more important factor than
      valence in determining whether emotion interferes with language output in
      individuals with schizophrenia. An affective reactivity task, comprising
      conditions separated by emotional valence (positive, negative) and arousal (low,
      high), was administered to 22 individuals with schizophrenia or schizoaffective
      disorder and 13 non-patient controls. Individuals with schizophrenia or
      schizoaffective disorder demonstrated variable reactivity to both valence
      arousal. Results suggest that high arousal content can be especially impairing to
      certain individuals, and it is those individuals with schizophrenia and
      schizoaffective disorder who demonstrate more depressive symptomatology that show
      the greatest affective reactivity to negatively valenced, high arousing
      information. Clarifying aberrant emotion processing in schizophrenia is crucial
      to understanding precursors to symptom exacerbation and to the consideration of
      optimal treatment strategies.

PMID- 17553675
TI  - Municipal solid waste characterizations and management strategies for the Lower
      Rio Grande Valley, Texas.
AB  - The Lower Rio Grande Valley (LRGV or Valley) in Texas, facing the big waste
      management challenge along the US-Mexico border today, is at the crossroads as a
      result of the rapid population growth, the scarcity of landfill space, the bi
      nation's trade impacts, and the illusive goal of environmental sustainability.
      This paper offers a unique municipal solid waste investigation with regard to
      both physical and chemical characteristics leading to illuminate the necessary
      management policies with greater regional relevancy. With multiple sampling
      campaigns conducted during the spring of 2005, this study holistically summarizes
      the composition of solid waste, the statistical distribution patterns of key
      recyclable items, and the heating value in an uncertain environment. Research
      findings indicate that high fractions of plastics and paper in the waste stream
      imply a strong potential for energy recovery. Incineration options are thus
      bolstered by mildly high heating values across 10 cities in this region, which
      may lead to save land resources required for final disposal and increase
      electricity generation in the long run. Additional regression analyses further
      identify the correlation between recyclable items and heating value, which show
      that current recycling programs permit no obvious negative impacts on the
      incineration option. Final statistical hypothesis tests for both the Brownsville
      Harlingen-San Benito and the McAllen-Edinburg-Mission metropolitan regions help
      foster consistent management strategies across the Valley regardless of the
      trivial differences of waste characteristics in between.

PMID- 17553676
TI  - Textural and surface chemical characteristics of activated carbons prepared from
      cattle manure compost.
AB  - Two activated carbons (ACs) prepared from cattle manure compost (CMC) by ZnCl(2)
      activation were selected and out-gassed in a helium flow at various temperatures
      for 2h. The pore structure and surface chemical properties of the two selected
      ACs and their out-gassing treated ACs were characterized using N(2) adsorption
      desorption, elements analysis, SEM and Boehm titration. A basic dye, methylene
      blue (MB), was chosen as an adsorbate to investigate the adsorption capacity for
      organic contaminant onto the activated carbons. It was found that the out-gassing
      treatment at 400 degrees C had little effect on the textural characteristics of
      the carbons but significantly changed the surface chemical properties such as
      surface functional groups concentration, pH and pH(PZC). The CMC-based activated
      carbons exhibited excellent performance for MB adsorption due to their high
      surface area, large mesopore volume and high nitrogen content. The kinetics of MB
      adsorption onto the activated carbons followed a pseudo-second-order equation,
      and the equilibrium data agreed well with the Langmuir model under the
      experimental conditions. The highest adsorption rate constant of k(ad) and the
      largest adsorption capacity of q(m) were found be 1.44x10(-4)g/mgmin and 519mg/g,
      respectively. The results suggested that the CMC-based activated carbons were
      effective adsorbents for the removal of methylene blue from aqueous solution.

PMID- 17553674
TI  - The ErbB4 receptor in fetal rat lung fibroblasts and epithelial type II cells.
AB  - ErbB receptors are important regulators of fetal organ development, including the
      fetal lung. They exhibit diversity in signaling potential, acting through homo-
      and heterodimers to cause different biological responses. We hypothesized that
      ErbB receptors show cell-specific and stimuli-specific activation,
      heterodimerization, and cellular localization patterns in fetal lung. We
      investigated this using immunoblotting, co-immunoprecipitation, and confocal
      microscopy in primary isolated E19 fetal rat lung fibroblasts and epithelial type
      II cells, stimulated with epidermal growth factor, transforming growth factor
      alpha, neuregulin 1beta, or treated with conditioned medium (CM) from the
      respective other cell type. Fetal type II cells expressed significantly more
      ErbB1, ErbB2, and ErbB3 protein than fibroblasts. ErbB4 was consistently
      identified by co-immunoprecipitation of all other ErbB receptors in both cell
      types independent of the treatments. Downregulation of ErbB4 in fibroblasts
      initiated cell-cell communication that stimulated surfactant phospholipid
      synthesis in type II cells. Confocal microscopy in type II cells revealed nuclear
      localization of all receptors, most prominently for ErbB4. Neuregulin treatment
      resulted in relocation to the extra-nuclear cytoplasmic region, which was
      distinct from fibroblast CM treatment which led to nuclear localization of ErbB4
      and ErbB2, inducing co-localization of both receptors. We speculate that ErbB4
      plays a prominent role in fetal lung mesenchyme-epithelial communication.

PMID- 17553677
TI  - Modulation of AP-1 mediated estrogenic response by ormeloxifene in rat uterus.
AB  - Ormeloxifene is a selective estrogen receptor modulator that exerts
      antiestrogenic effects and thereby inhibits growth in uterus. The present study
      was undertaken to examine the AP-1 protein interaction with AP-1 enhancer DNA
      elements in rat uterus in vivo and in vitro with a view to explore the modulation
      of estrogen action mediated via alternative pathway under the influence of
      ormeloxifene (Orm). In addition, the changes in expression of c-fos and c-jun
      transcription factors and mRNA expression of growth factor (IGF-1) were
      investigated with a view to assess the AP-1 mediated transcription.
      Ovariectomizedoung adult rats were administered with estradiol-17beta (5
      microg/100 g body weight) or Orm (200 microg/100 g body weight) or vehicle for 3
      days and sacrificed on fourth day. Electrophoretic mobility shift assay using
      uterine nuclear fraction from various treatment groups demonstrated that Orm
      caused a significant reduction in E2 induced AP-1 DNA binding. In vitro study
      revealed that Orm promotes AP-1 complex formation whereas its 7-hydroxy
      derivative inhibits it significantly. Uterine expression of c-fos and c-jun was
      increased significantly in Orm treated rats as compared to vehicle treated rats.
      However, the expression of c-fos and c-jun was decreased in rats receiving Orm
      plus E2. Semi-quantitative RT-PCR analysis revealed that mRNA expression of IGF-1
      was increased in E2 treated group as compared to control group whereas reduced
      expression was observed in Orm treated rats as compared to E2 treated rats. The
      uterine weight and IGF-1 mRNA showed similar pattern, indicating that IGF-1 is
      involved in regulation of uterine weight. These results indicate that 7-hydroxy
      ormeloxifene (an active metabolite of Orm) is a potent antagonist at AP-1 sites.
      It inhibits the function of AP-1 transcription factors rather than their
      expression as evident by downregulation of mRNA expression of AP-1 regulated gene
      IGF-1, thereby inhibits proliferation in rat uterus. Study suggested a non
      classicalregulation of estrogen action on uterus by ormeloxifene.

PMID- 17553678
TI  - Design and synthesis of highly potent and selective human peroxisome proliferator
      activated receptor alpha agonists.
AB  - A combination of benzoxazole, phenoxyalkyl side chain, and phenoxybutyric acids
      was identified as a highly potent and selective human peroxisome proliferator
      activated receptor alpha (PPARalpha) agonist. The synthesis, structure-activity
      relationship (SAR) studies, and in vivo activities of the representative
      compounds are described.

PMID- 17553679
TI  - 5(Z)-benzylidene-1,2-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5H-1-aza-6-oxa
      chrysenes as non-steroidal glucocorticoid receptor modulators.
AB  - A series of 5-benzylidene-1,2-dihydro-2,2,4-trimethyl-5H-1-aza-6-oxa-chrysenes
      was synthesized and profiled for their ability to act as selective glucocorticoid
      receptor modulators (SGRMs). The synthesis and structure-activity relationships
      for this series of compounds are presented.

PMID- 17553680
TI  - Antimicrobial activity of rationally designed amino terminal modified peptides.
AB  - Series of short amino terminal modified cationic peptides were designed and
      synthesized. All of the synthesized compounds were tested against gram-positive
      as well as gram-negative bacterial strain. Some of the compounds exhibit potent
      antibacterial activity and no hemolytic activity even at high dose level (1000
      microg/mL) in mammalian erythrocytes was observed.

PMID- 17553681
TI  - Novel selective PPARdelta agonists: optimization of activity by modification of
      alkynylallylic moiety.
AB  - Y-shaped molecules bearing alkynylallylic moieties were found to be potent and
      selective PPARdelta activators. The alkynylallylic moiety was synthesized from
      alkyn-1-ols by hydroalumination followed by a cross-coupling reaction. Series of
      active compounds 6 were obtained by stepwise changing the structure of the known
      PPARpan agonist 5 into Y-shaped compounds. The most active and selective
      compound, 6f, had a PPARdelta potency of 0.13 microM, which is 50-fold more
      potent than compound 5.

PMID- 17553682
TI  - 3D-QSAR studies on sildenafil analogues, selective phosphodiesterase 5
      inhibitors.
AB  - Sildenafil, one of selective phosphodiesterase 5 (PDE5) inhibitors, is a widely
      used oral agent for the treatment of erectile dysfunction. To develop new PDE5
      inhibitors with improved therapeutic efficacy, a series of sildenafil analogues
      have been prepared and their in vitro PDE5 inhibitory activities were evaluated.
      Their IC(50) values ranged from 423 to 0.05 nM. Herein, the results of 3D-QSAR
      (CoMFA and CoMSIA) analyses on these inhibitors are reported. Both CoMFA and
      CoMSIA gave reliable models with q(2) values >0.75 and r(2) values >0.99. The
      resulting CoMFA and CoMSIA models reveal a good correlation between the contour
      maps and the active site residues critical for the interaction with inhibitor,
      and nicely predict the key structural features of new analogues with improved
      activity and selectivity.

PMID- 17553683
TI  - Reliability of a simple fluoroscopic method to study sagittal plane femorotibial
      contact changes in total knee arthroplasties during flexion.
AB  - Clinical interest in sagittal plane kinematic analysis of the knee undergoing
      total knee replacement fosters the development of simple, reliable methods to
      estimate femorotibial contact in a regular clinical setting. In this study, the
      sagittal femorotibial contact was analysed in lateral X-rays and lateral
      fluoroscopic views, from extension to knee flexion. Quantitative and categorical
      data were obtained from these views by two different observers, and compared with
      data from direct views of the components. Interobserver and intermethod errors
      for quantitative and categorical data were evaluated based on correlation, kappa
      coefficient, and Bland-Altman graphs. Interobserver reproducibility of
      quantitative measurement from fluoroscopic views was r=0.96 while categorical
      assignment exhibited a kappa coefficient of 0.95. Reproducibility from plain
      radiographs was not so high, with a kappa coefficient of 0.64. High concordance
      was also obtained when the method was compared with the direct view of the
      implant, supporting these measurement techniques. Bland-Altman graphs confirmed
      the absence of bias in the intermethod comparison. Therefore, with the obvious
      limitation of rotational assessment, lateral fluoroscopic evaluation enhanced by
      a simple fitting technique can be used as a valuable tool for clinical evaluation
      of knee kinematics in the sagittal plane.

PMID- 17553684
TI  - New amino and acetamido monomethine cyanine dyes for the detection of DNA in
      agarose gels.
AB  - Some new monomethine cyanine dyes derived from quinoline and benzothiazole have
      been prepared and characterized by (1)H and (13)C NMR, FTIR, FABHRMS, and visible
      spectroscopy. The dyes containing amino and acetamido groups were conveniently
      synthesized by the condensation of two p-toluenesulfonate heterocyclic quaternary
      salts and were obtained in the forms of iodide, bromide, and tosylate
      counteranions. These dyes were compared to ethidium bromide as stains for DNA in
      electrophoretic gels. The overall results obtained for the sensitivity of these
      dyes suggest the suitability of acetamido moiety over the amine one and bromide
      as the counteranion when compared with iodide and tosylate, with a similar
      capacity of DNA detection in relation to the ethidium bromide stain over the
      concentration range of 1-3ng.

PMID- 17553685
TI  - Characterized mechanism of alpha-mangostin-induced cell death: caspase
      independent apoptosis with release of endonuclease-G from mitochondria and
      increased miR-143 expression in human colorectal cancer DLD-1 cells.
AB  - alpha-Mangostin, a xanthone from the pericarps of mangosteen (Garcinia mangostana
      Linn.), was evaluated for in vitro cytotoxicity against human colon cancer DLD-1
      cells. The number of viable cells was consistently decreased by the treatment
      with alpha-mangostin at more than 20 microM. The cytotoxic effect of 20 microM
      alpha-mangostin was found to be mainly due to apoptosis, as indicated by
      morphological findings. Western blotting, the results of an apoptosis inhibition
      assay using caspase inhibitors, and the examination of caspase activity did not
      demonstrate the activation of any of the caspases tested. However, endonuclease-G
      released from mitochondria with the decreased mitochondrial membrane potential
      was shown. The levels of phospho-Erk1/2 were increased in the early phase until
      1h after the start of treatment and thereafter decreased, and increased again in
      the late phase. On the other hand, the level of phospho-Akt was sharply reduced
      with the process of apoptosis after 6h of treatment. Interestingly, the level of
      microRNA-143, which negatively regulates Erk5 at translation, gradually increased
      until 24h following the start of treatment. We also examined the synergistic
      growth suppression in DLD-1 cells by the combined treatment of the cells with
      alpha-mangostin and 5-FU which is one of the most effective chemotherapeutic
      agents for colorectal adenocarcinoma. The co-treatment with alpha-mangostin and 5
      FU, both at 2.5 microM, augmented growth inhibition compared with the treatment
      with 5 microM of alpha-mangostin or 5 microM 5-FU alone. These findings indicate
      unique mechanisms of alpha-mangostin-induced apoptosis and its action as an
      effective chemosensitizer.

PMID- 17553686
TI  - Severe deficiency of the fatty acid amide hydrolase (FAAH) activity segregates
      with the Huntington's disease mutation in peripheral lymphocytes.
AB  - The search for peripheral markers of neurodegenerative diseases aims at
      identifying molecules that could help in monitoring the effects of future
      therapeutics in easily accessible cells. Here we focused on the involvement of
      the endocannabinoid system in Huntington's disease (HD). We assayed peripheral
      lymphocytes from HD patients and healthy controls, and found that the activity of
      the fatty acid amide hydrolase (FAAH), the enzyme that degrades the
      endocannabinoid anandamide (AEA), was dramatically decreased (down to less than
      10%) in HD compared to healthy subjects. Concomitantly, the endogenous levels of
      AEA were approximately 6-fold higher in HD versus healthy lymphocytes, while the
      other elements of the endocannabinoid system were not affected by HD. Low FAAH
      activity in HD lymphocytes was not due to down-regulation of protein expression,
      but rather to blockage of enzyme activity by a cytosolic and irreversible
      inhibitor. Finally, pre-HD patients showed defective FAAH activity, as did the
      brain of HD patients compared with healthy controls. Taken together, our data
      indicate that FAAH activity in lymphocytes mirrors some of the metabolic changes
      which take place in the brain, it is a measurable non-genetic peripheral marker
      that segregates with the HD mutation, and it might serve as a target to test
      chemicals active on the widespread toxic effects of the mutant protein.

PMID- 17553687
TI  - Cannulation of the innominate artery during surgery of the thoracic aorta: our
      experience in 55 patients.
AB  - BACKGROUND: Alternative cannulation sites such as the right/left axillary artery,
      the ascending aorta and aortic arch have been recently preferred to the femoral
      artery to improve neurologic outcome in patients undergoing surgery of the
      thoracic aorta. In 2004, we started to select the innominate artery as an
      arterial cannulation site for CPB and antegrade cerebral perfusion institution.
      Here we present our preliminary experience with 55 patients. METHODS: Between
      November 2004 and 2006, 55 patients (mean age 60+/-14 years) underwent surgery on
      the thoracic aorta using the innominate artery as a site for arterial
      cannulation. Indication for surgery was a degenerative aneurysm in 49 (89.1%), an
      acute type A dissection in 2 patients (3.6%), a post-dissection aneurysm in 3
      (5.4%), a supravalvular aortic stenosis in 1 patient (1.8%). Operative procedure
      included total arch replacement (n=9), hemiarch replacement (n=6), ascending
      aorta replacement (n=21), Bentall procedure (n=18) and aortoplasty with patch
      (n=1). Mean CPB and cross clamp times were 131+/-60 and 95+/-29 min,
      respectively. Mean cerebral perfusion time was 54+/-26 min. RESULTS: The hospital
      mortality rate was 3.6%. There were no permanent neurologic dysfunction and one
      (1.8%) temporary neurological dysfunction. CONCLUSION: Our results with the
      cannulation of the innominate artery were encouraging. This provides the same
      advantages of the axillary artery cannulation with greater simplicity and
      avoiding extra surgical incisions which may be site for local complications. It
      may represent a valid option for CPB and antegrade cerebral perfusion institution
      in aortic procedures.

PMID- 17553688
TI  - Beta-blockade at low doses restoring the physiological balance in myocytic
      antagonism.
AB  - OBJECTIVE: The ventricular mass is organized in the form of meshwork, with
      populations of myocytes aggregated in a supporting matrix of fibrous tissue, with
      some myocytes aligned obliquely across the wall so as to work in an antagonistic
      fashion compared to the majority of myocytes, which are aggregated together in
      tangential alignment. Prompted by results from animal experiments, which showed a
      disparate response of the two populations of aggregated myocytes to negative
      inotropic medication, we sought to establish whether those myocytes that
      aggregated so as to extend obliquely across the thickness of the ventricular
      walls are more sensitive to beta-blockade than the prevailing population in which
      the myocytes are aggregated together with tangential alignment. If the two
      populations respond in similar differing fashion in the clinical situation, we
      hypothesize that this might help to explain why drugs blocking the beta-receptors
      improve function of the ventricular pump in the setting of congestive cardiac
      failure. METHODS: We implanted needle probes in 13 patients studied during open
      heart surgery, measuring the forces generated in the ventricular wall and seeking
      to couple the probes either to myocytes aggregated together with tangential
      alignment or to those aggregated in oblique fashion across the ventricular walls.
      In a first series of patients, we injected probatory doses intravenously,
      amounting to a total bolus of 40-100mg Esmolol, while in a second series, we gave
      fixed yet rising doses of 5, 10, and 20mg Esmolol in three separate boluses.
      RESULTS: Forces recorded in the aggregated myocytes with tangential alignment
      decreased insignificantly upon administration of low doses (57.1+/-12.4 mN-
      >56.6+/-7.6 mN), while forces recorded in the myocytes aggregated obliquely
      across the ventricular wall showed a significant decrease in the mean (59.3+/
      11.6 mN-->47.4+/-6.4 mN). CONCLUSIONS: The markedly disparate action of drugs
      blocking beta-receptors at low dosage seems to be related to the heterogeneous
      extent, and time course, of systolic loading of the myocytes. This, in turn,
      depends on whether the myocytes themselves are aggregated together with
      tangential or oblique alignments relative to the thickness of the ventricular
      walls.

PMID- 17553689
TI  - A comparison of quantitative and qualitative superoxide dismutase assays for
      application to low temperature microalgae.
AB  - Antioxidant enzymes such as superoxide dismutase (SOD) play a key role in the
      removal of reactive oxygen species produced during visible and ultraviolet
      irradiance stress in microalgae and plants. However, little is known about the
      enzymatic antioxidative stress responses in ecologically important Antarctic
      marine microalgae. SOD in particular is difficult to analyze, possibly due to
      problems in obtaining sufficient quantities necessary for reliable and
      reproducible enzymatic assays. The aim of the present work was to create a
      sensitive, easy-to-use and reliable method for SOD determination in Antarctic
      microalgal material by comparing and optimizing existing protein extraction
      procedures and SOD assays in the marine Antarctic diatom Chaetoceros brevis.
      Optimization was achieved in cell disruption (sonication) and protein extraction
      procedures, extraction buffers, SOD assay methods (xanthine/xanthine oxidase and
      NBT/riboflavin photometric quantitative methods and native gel electrophoresis
      qualitative method) and the assay temperature. Protein extraction was optimal at
      low sonication amplitudes after a few pulses, irrespective of the type of buffer
      used. Extraction efficiency varied highly between the tested buffers; most
      protein was extracted in the presence of 1% of Triton X-100. SOD activity was
      best quantified using the NBT/riboflavin method in combination with a buffer
      containing potassium phosphate and Triton X-100. Moreover, the NBT/riboflavin
      method was demonstrated to be the most reliable and sensitive method at low
      temperatures (5 degrees C).

PMID- 17553690
TI  - Attitudes towards predictive genetic testing in minors for familial breast
      cancer: a systematic review.
AB  - OBJECTIVES: The objective of this article is to review the attitudes of different
      stakeholders (minors, parents, healthcare professionals, and relatives of
      affected individuals) towards predictive genetic testing of minors for familial
      breast cancer. DESIGN: The databases PubMed, Google Scholar, Psychinfo,
      Biological Abstracts, Francis, Anthropological Index online, Web of Science, and
      Sociological Abstracts were searched using relevant key words; literature indexed
      up to May 2006 was considered. Studies were included if they were published in a
      peer-reviewed journal written in English and if they described the attitudes of
      the different stakeholders towards predictive genetic testing of minors for
      familial breast cancer. The results are presented in a summary form. RESULTS: A
      total of 14 studies were included. The studies were very heterogeneous, using a
      variety of study populations, study designs, sample sizes, and study measures.
      Substantial proportions of adolescents were interested in learning whether they
      were at risk for familial breast cancer. The attitudes of healthcare
      professionals about testing minors diverged. CONCLUSION: Our review has made
      clear that many respondents fail to understand potential risks related to
      predictive genetic testing in minors. Respondents might have overly positive
      expectations about possibilities for genetic testing. This emphasizes the need
      for genetic education and counselling about genetic testing in minors.

PMID- 17553691
TI  - The aging brain, a key target for the future: the protein kinase C involvement.
AB  - The brain represents the primary centre for the regulation and control of all our
      body activities, receiving and interpreting sensory impulses and transmitting
      information to the periphery. Most importantly, it is also the seat of
      consciousness, thought, emotion and especially memory, being in fact able to
      encode, store and recall any information. Memory is really what makes possible so
      many of our complex cognitive functions, including communication and learning,
      and surely without memory, life would lose all of its glamour and purpose. Age
      associated mental impairment can range in severity from forgetfulness at the
      border with pathology to dementia, such as in Alzheimer's disease. In recent
      years, one of the most relevant observations of research on brain aging relates
      to data indicating that age-related cognitive decline is not only due to neuronal
      loss, as previously thought; instead, scientists now believe that age-associated
      functional changes have more to do with the dysfunctions occurring over time.
      Within this context a prominent role is certainly played by signal transduction
      cascades which guarantee neuronal cell to elaborate coordinated responses to the
      multiple signals coming from the outside and to adapt itself to the environmental
      changes and requests. This review will focus the attention on protein kinase C
      pathway, with a particular interest on its activation process, and on the role of
      protein-lipid and protein-protein interactions to selectively localize the
      cellular responses. Furthermore, information is emerging and will be discussed on
      the possibility of mRNA stabilization through PKC activation. This review will
      also approach the issue on how alterations of these molecular cascades may have
      implications in physiological and pathological brain aging, such as Alzheimer's
      disease.

PMID- 17553692
TI  - Mapping the human plasma proteome by SCX-LC-IMS-MS.
AB  - The advent of on-line multidimensional liquid chromatography-mass spectrometry
      has significantly impacted proteomic analyses of complex biological fluids such
      as plasma. However, there is general agreement that additional advances to
      enhance the peak capacity of such platforms are required to enhance the accuracy
      and coverage of proteome maps of such fluids. Here, we describe the combination
      of strong-cation-exchange and reversed-phase liquid chromatographies with ion
      mobility and mass spectrometry as a means of characterizing the complex mixture
      of proteins associated with the human plasma proteome. The increase in separation
      capacity associated with inclusion of the ion mobility separation leads to
      generation of one of the most extensive proteome maps to date. The map is
      generated by analyzing plasma samples of five healthy humans; we report a
      preliminary identification of 9087 proteins from 37,842 unique peptide
      assignments. An analysis of expected false-positive rates leads to a high
      confidence identification of 2928 proteins. The results are catalogued in a
      fashion that includes positions and intensities of assigned features observed in
      the datasets as well as pertinent identification information such as protein
      accession number, mass, and homology score/confidence indicators. Comparisons of
      the assigned features reported here with other datasets shows substantial
      agreement with respect to the first several hundred entries; there is far less
      agreement associated with detection of lower abundance components.

PMID- 17553693
TI  - Ca2+, CREB and kruppel: a novel KLF7-binding element conserved in mouse and human
      TRKB promoters is required for CREB-dependent transcription.
AB  - Brain-derived neurotrophic factor (BDNF) signaling through its receptor, trkB, is
      essential for the proper development and function of the nervous system. Here we
      identify a novel regulatory element designated TCaRE3 (TRKB Ca(2+) response
      element 3) required for CREB-dependent TRKB transcription in neurons. TCaRE3
      inactivating mutations abolished both Ca(2+)- and cAMP-stimulated TRKB
      expression, despite the presence of upstream CREs. TCaRE3 mutations also reduced
      basal expression by at least 80%. Electrophoretic mobility shift assays revealed
      the presence of a neuronal nuclear factor able to bind TCaRE3 in a sequence
      specific manner and we have identified kruppel-like factor 7 (KLF7) as a
      candidate TCaRE3 transcription factor. Importantly, despite limited overall
      sequence homology between the promoter regions of the human and mouse TRKB genes,
      TCaRE3 exhibits 100% sequence identity. Mutation analysis of the human TRKB
      promoter region demonstrated that the role of TCaRE3 is also conserved,
      suggesting that the functional interaction between CREB bound to the CREs and
      KLF7 bound to TCaRE3 is essential for the proper regulation of TRKB in neurons.

PMID- 17553694
TI  - Purinergic receptor activation inhibits mitogen-stimulated proliferation in
      primary neurospheres from the adult mouse subventricular zone.
AB  - The expression pattern of purinergic receptors was examined in subventricular
      zone-derived primary neurospheres. Primary neurospheres expressed mRNA for P2X4
      and P2X7 receptors, all P2Y receptors, with the exception of P2Y4, and the A1,
      A2a and A2b adenosine receptors. ATPgammaS, ADPbetaS and UTP evoked transient
      increases in cytoplasmic Ca(2+) concentration in dissociated primary
      neurospheres, demonstrating the functional expression of P2Y1 and P2Y2 receptors.
      Ca(2+) transients were not attenuated by the removal of extracellular Ca(2+) and
      were reversibly inhibited by the P2Y1 selective antagonist, MRS 2179. P2Y and
      adenosine receptor agonists reduced the size and frequency of primary
      neurospheres. The effects of ADPbetaS and adenosine were reversed by subtype
      selective receptor antagonists, demonstrating that P2Y1 and A2a receptors mediate
      inhibitory effects on primary neurosphere proliferation. The modulation of neural
      precursor cell proliferation by P2Y and adenosine receptors therefore represents
      a potential regulatory mechanism within the neurogenic microenvironment.

PMID- 17553695
TI  - Cadherin inhibition of beta-catenin signaling regulates the proliferation and
      differentiation of neural precursor cells.
AB  - The generation and differentiation of neurons during development requires
      coordination of intercellular interactions with spatio-temporal changes in gene
      expression. To examine the role of adhesion in cerebral cortical development, we
      overexpressed full-length cadherin and dominant-negative truncated cadherin in
      mouse cortical precursors. Full-length cadherin allowed for the maintenance of
      cell contact between daughter cells following cell division while dominant
      negative cadherin decreased cell contact. Paradoxically, both cadherin isoforms
      inhibited precursor proliferation, induced premature neuronal differentiation,
      and inhibited beta-catenin dependent signaling. Furthermore, alteration of
      cadherin or beta-catenin function led to additional changes in precursor identity
      and division symmetry as demonstrated by altered expression of the radial glial
      marker, Pax6, and the intermediate precursor marker, Tbr2. Moreover, clonal
      analysis demonstrated asymmetric distribution of Tbr2 following precursor
      mitosis. Together, these results show that cadherins affect neural precursor fate
      determination through a cell-autonomous regulation of catenin signaling distinct
      from cadherin adhesive function.

PMID- 17553696
TI  - Purification and characterization of the bifunctional uridylyltransferase and the
      signal transducing proteins GlnB and GlnK from Herbaspirillum seropedicae.
AB  - GlnD is a bifunctional uridylyltransferase/uridylyl-removing enzyme that has a
      central role in the general nitrogen regulatory system NTR. In enterobacteria,
      GlnD uridylylates the PII proteins GlnB and GlnK under low levels of fixed
      nitrogen or ammonium. Under high ammonium levels, GlnD removes UMP from these
      proteins (deuridylylation). The PII proteins are signal transduction elements
      that integrate the signals of nitrogen, carbon and energy, and transduce this
      information to proteins involved in nitrogen metabolism. In Herbaspirillum
      seropedicae, an endophytic diazotroph isolated from grasses, several genes coding
      for proteins involved in nitrogen metabolism have been identified and cloned,
      including glnB, glnK and glnD. In this work, the GlnB, GlnK and GlnD proteins of
      H. seropedicae were overexpressed in their native forms, purified and used to
      reconstitute the uridylylation system in vitro. The results show that H.
      seropedicae GlnD uridylylates GlnB and GlnK trimers producing the forms PII
      (UMP)(1), PII (UMP)(2) and PII (UMP)(3), in a reaction that requires 2
      oxoglutarate and ATP, and is inhibited by glutamine. The quantification of these
      PII forms indicates that GlnB was more efficiently uridylylated than GlnK in the
      system used.

PMID- 17553697
TI  - Body mass index and mortality in South Korean men resulting from cardiovascular
      disease: a Kangwha cohort study.
AB  - PURPOSE: The purpose of this study was to examine the association of body mass
      index (BMI) with death caused by total cardiovascular disease in a long-term
      follow-up study. METHODS: We followed a total of 2608 men who were 55 years or
      older in 1985 from March 1985 through December 2001 to investigate their
      mortality. The hazard ratios of mortality as the result of cardiovascular disease
      by BMI level were estimated with the Cox proportional hazards model, adjusting
      for relevant covariates. RESULTS: For the group with a BMI >/= 27 kg/m(2)
      compared with the reference group (BMI, 21.0-22.9), the adjusted hazard ratio of
      death resulting from total cardiovascular disease was 2.4 (95% confidence
      interval [CI], 1.5-3.9) and that of death resulting from cerebrovascular disease
      was 3.6 (95% CI, 2.0-6.3). Observing nonsmoking subjects only, the BMI <18.5
      kg/m(2) group had a 4.6 times (95% CI, 1.8-11.8) greater risk of death attributed
      to total cardiovascular disease than the reference group and a 4.7 times (95% CI,
      1.4-16.2) greater risk of death from cerebrovascular disease. CONCLUSION: This
      study defined that BMI is related to Korean male deaths caused by total
      cardiovascular disease. The risk of death attributed to total cardiovascular
      disease and cerebrovascular disease was significantly increased in the group,
      with a BMI >/=27 kg/m(2). In our study, in the case of nonsmokers, low BMI was
      shown to be related to deaths from cardiovascular disease. Such result is
      different from those of previous studies.

PMID- 17553698
TI  - Regarding "menstrual and reproductive risk factors and risk for gastric
      adenocarcinoma in women: findings from the canadian national enhanced cancer
      surveillance system".

PMID- 17553699
TI  - Comments on Brewer et al., "Male and female circumcision associated with
      prevalent HIV infection in virgins and adolescents in Kenya, Lesotho, and
      Tanzania".

PMID- 17553700
TI  - Cardiovascular health among adults in Syria: a model from developing countries.
AB  - PURPOSE: Despite the considerable mortality and morbidity associated with
      cardiovascular disease (CVD), many developing countries lack reliable
      surveillance of these ailments and their risk factors to guide intervention. This
      study aims to provide the first population-based estimates of CVD morbidity and
      mortality among adults in Aleppo, Syria and the distribution of their risk
      factors. METHODS: A cross-sectional survey of adults 18 to 65 years old residing
      in Aleppo, Syria was carried out in 2004, involving 2038 household
      representatives (45.2% men; mean age, 35.3 years; response rate, 86%). Main
      outcomes of interest were physician-diagnosed CVD (infarction, angina, failure,
      stroke) among survey participants, and past 5-year mortality due to CVD among
      their household members older than 20 years of age (N = 6252, 49.5% men).
      Measurement of blood pressure (BP), height and weight, and smoking history were
      obtained as well. RESULTS: Prevalence of CVD was 4.8% for heart disease and 1.0%
      for stroke. CVD was responsible for 45.0% of overall mortality reported in the
      past 5 years, whereby 49% of CVD deaths occurred before the age of 65 years. Mean
      age of death was 62.6 years (63.6 years for heart disease and 61.4 years for
      stroke). Annual crude death rate due to CVD was 314 per 100,000 (95% confidence
      interval [95% CI]: 215-414); of these, 179 were due to heart disease, and 135 due
      to stroke. More men than women died from heart disease, whereas the opposite was
      true for stroke. Hypertension was detected in 40.6% (47.7% men, 34.9%women),
      obesity in 38.2% (28.8% men, 46.4% women), and smoking (cigarettes or waterpipe)
      in 38.7% (63.6% men, 19.2% women) of participants. Of those surveyed, 39.3% had
      one CVD risk factor, 27.4% had two risk factors, and 8.3% had 3 risk factors.
      Main predictors of clustering of risk factors were older age, male gender, and
      low education. CONCLUSIONS: Syria is currently undergoing a stage in which
      morbidity and mortality from CVD are high but likely to increase based on the
      population's risk profile. CVD risk distribution in Syrian society highlights the
      non-generalizability of CVD models from developed societies, and calls for local
      studies to inform effective interventions and policies.

PMID- 17553701
TI  - Design and simulation study of the immunization Data Quality Audit (DQA).
AB  - The goal of the Data Quality Audit (DQA) is to assess whether the Global Alliance
      for Vaccines and Immunization-funded countries are adequately reporting the
      number of diphtheria-tetanus-pertussis immunizations given, on which the "shares"
      are awarded. Given that this sampling design is a modified two-stage cluster
      sample (modified because a stratified, rather than a simple, random sample of
      health facilities is obtained from the selected clusters); the formula for the
      calculation of the standard error for the estimate is unknown. An approximated
      standard error has been proposed, and the first goal of this simulation is to
      assess the accuracy of the standard error. Results from the simulations based on
      hypothetical populations were found not to be representative of the actual DQAs
      that were conducted. Additional simulations were then conducted on the actual DQA
      data to better access the precision of the DQ with both the original and the
      increased sample sizes.

PMID- 17553702
TI  - Participation rates in epidemiologic studies.
AB  - Participation rates for epidemiologic studies have been declining during the past
      30 years with even steeper declines in recent years. This wholesale decrease in
      participation rate, or at the very least the increase in refusal, has, quite
      understandably, occasioned some concern among epidemiologists who have long
      considered a high study participation rate as one of the hallmarks of a "good"
      epidemiologic study. In this review we synthesize the issues that are central to
      epidemiologic thinking around declining study participation rates. We consider
      the reasons why study participation has been declining, summarize what we know
      about who does participate in epidemiologic studies, and discuss the implications
      of declining participation rates. We conclude with a discussion of methods that
      may help improve study participation rates.

PMID- 17553703
TI  - Integrating social and biologic factors in health research: a systems view.
AB  - An important focus of recent calls for interdisciplinary approaches in health
      research has been the integration of social and biomedical sciences in
      understanding the causes of ill-health. Typical models for the incorporation of
      social factors into biomedical research include social factors as distal
      antecedents of more proximate biologic factors and gene-environment interaction.
      Under both models the distinction between social and biologic factors remains
      clear-cut, and consideration of social factors is not indispensable for
      understanding the biologic processes leading to disease. However, recent evidence
      suggests that social and biologic processes are inextricably linked in systems.
      This paper reviews models for the incorporation of social factors into the study
      of health, discusses the potentialities of systems approaches, and highlights
      implications for population health and epidemiology.

PMID- 17553704
TI  - The cognitive control network: Integrated cortical regions with dissociable
      functions.
AB  - Consensus across hundreds of published studies indicates that the same cortical
      regions are involved in many forms of cognitive control. Using functional
      magnetic resonance imaging (fMRI), we found that these coactive regions form a
      functionally connected cognitive control network (CCN). Network status was
      identified by convergent methods, including: high inter-regional correlations
      during rest and task performance, consistently higher correlations within the CCN
      than the rest of cortex, co-activation in a visual search task, and mutual
      sensitivity to decision difficulty. Regions within the CCN include anterior
      cingulate cortex/pre-supplementary motor area (ACC/pSMA), dorsolateral prefrontal
      cortex (DLPFC), inferior frontal junction (IFJ), anterior insular cortex (AIC),
      dorsal pre-motor cortex (dPMC), and posterior parietal cortex (PPC). We used a
      novel visual line search task which included periods when the probe stimuli were
      occluded but subjects had to maintain and update working memory in preparation
      for the sudden appearance of a probe stimulus. The six CCN regions operated as a
      tightly coupled network during the 'non-occluded' portions of this task, with all
      regions responding to probe events. In contrast, the network was differentiated
      during occluded search. DLPFC, not ACC/pSMA, was involved in target memory
      maintenance when probes were absent, while both regions became active in
      preparation for difficult probes at the end of each occluded period. This
      approach illustrates one way in which a neuronal network can be identified, its
      high functional connectivity established, and its components dissociated in order
      to better understand the interactive and specialized internal mechanisms of that
      network.

PMID- 17553705
TI  - Functional anatomy of motor urgency.
AB  - This PET H(2)(15)O study uses a reaching task to determine the neural basis of
      the unconscious motor speed up observed in the context of urgency in healthy
      subjects. Three conditions were considered: self-initiated (produce the fastest
      possible movement toward a large plate, when ready), externally-cued (same as
      self-initiated but in response to an acoustic cue) and temporally-pressing (same
      as externally-cued with the plate controlling an electromagnet that prevented a
      rolling ball from falling at the bottom of a tilted ramp). Results show that: (1)
      Urgent responses (Temporally-pressing versus Externally-cued) engage the left
      parasagittal and lateral cerebellar hemisphere and the sensorimotor cortex (SMC)
      bilaterally; (2) Externally-driven responses (Externally-cued versus Self
      initiated) recruit executive areas within the contralateral SMC; (3) Volitional
      responses (Self-initiated versus Externally-cued) involve prefrontal cortical
      areas. These observations are discussed with respect to the idea that
      neuromuscular energy is set to a submaximal threshold in self-determined
      situations. In more challenging tasks, this threshold is raised and the first
      answer of the nervous system is to optimize the response of the lateral (i.e.
      crossed) corticospinal tract (contralateral SMC) and ipsilateral cerebellum. In a
      second step, the anterior (i.e. uncrossed) corticospinal tract (ipsilateral SMC)
      and the contralateral cerebellum are recruited. This recruitment is akin to the
      strategy observed during recovery in patients with brain lesions.

PMID- 17553706
TI  - A structural neural deficit in adolescents with conduct disorder and its
      association with lack of empathy.
AB  - The goal of this study was to determine whether brain regions implicated in
      emotion processing show structural alterations in adolescents with conduct
      disorder (CD). Using an optimized voxel-based morphometry protocol, we compared
      grey matter volume in 12 patients with CD and 12 age-, sex-, and intelligence
      matched control subjects. Grey matter volume in bilateral anterior insular cortex
      and the left amygdala was significantly reduced in CD patients compared to
      healthy control subjects. The insular grey matter abnormalities could be
      attributed to aggressive behaviour. Moreover, bilateral anterior insular grey
      matter volume in CD patients correlated significantly with empathy scores. These
      novel findings point at a joint neuroanatomical substrate underpinning aggressive
      behaviour and impaired capacity of empathy and suggest a critical role for the
      anterior insula in regulating social behaviour.

PMID- 17553707
TI  - Phylogenetic relationships of coexisting Heterocypris (Crustacea, Ostracoda)
      lineages with different reproductive modes from Lampedusa Island (Italy).
AB  - Coexisting bisexual and unisexual populations of individuals belonging to the
      genus Heterocypris are found in ephemeral freshwater ponds on the island of
      Lampedusa (Pelagie Islands, Italy). Different reproductive modes were associated
      with a peculiar morphological trait: a lamella hyalina on the posterior margin of
      the left valve was observed in amphimictic females, a feature missing in
      apomictic females. In order to clarify the phylogenetic relationships among taxa
      with different morphological traits and reproductive modes, we used four
      polymorphic enzyme loci (GPI, ICD2, MPI and PGM) and mitochondrial DNA 16S
      ribosomal sequences. We identified three main evolutionary units that showed a
      combination of morphological and reproductive characteristics: (1) amphimictic
      females of H. barbara with a lamella hyalina, according to the typical feature of
      the species, and apomictic females of H. barbara without lamella that are
      sympatric in one temporary pond; (2) apomictic females of H. incongruens without
      a lamella, as typical of the species; (3) apomictic females without a lamella,
      living in sympatry with H. barbara, but characterised by a high genetic diversity
      from both H. incongruens and H. barbara. We discuss the possible origin of
      apomictic lineages as a result of independent transition episodes to apomixis
      from different sexual ancestors. Time of divergence reflected the genetic
      differentiation within and among multiple ancestors and different possible routes
      to parthenogenesis.

PMID- 17553708
TI  - Bridging the Rubicon: phylogenetic analysis reveals repeated colonizations of
      marine and fresh waters by thalassiosiroid diatoms.
AB  - Salinity imposes a significant barrier to the distribution of many organisms,
      including diatoms. Diatoms are ancestrally marine, and the number of times they
      have independently colonized fresh waters and the physiological adaptations that
      facilitated these transitions remain outstanding questions in diatom evolution.
      The colonization of fresh waters by diatoms has been compared to "crossing the
      Rubicon," implying that successful colonization events are rare, irreversible,
      and lead to substantial species diversification. To test these hypotheses, we
      reconstructed the phylogeny of Thalassiosirales, a diatom lineage with high
      diversity in both marine and fresh waters. We collected approximately 5.3kb of
      DNA sequence data from the nuclear (SSU and partial LSU rDNA) and chloroplast
      genomes (psbC and rbcL) and reconstructed the phylogeny using parsimony and
      Bayesian methods. Alternative topology tests strongly reject all previous
      colonization hypotheses, including monophyly of the predominantly freshwater
      Stephanodiscaceae. Results showed at least three independent colonizations of
      fresh waters, and whereas previous accounts of freshwater-to-marine transitions
      have been discounted, these results provide compelling evidence for as many as
      three independent re-colonizations of the marine habitat, two of which led to
      speciation events. This study adds valuable phylogenetic context to previous
      debate about the nature of the salinity barrier in diatoms and provides
      compelling evidence that, at least for Thalassiosirales, the salinity barrier
      might be less formidable than previously thought.

PMID- 17553709
TI  - Understanding the biology of angiogenesis: review of the most important molecular
      mechanisms.
AB  - Angiogenesis is an important process for forming new blood vessels. It is
      fundamental in many biological processes including development, reproduction and
      wound repair. Under these conditions, angiogenesis is a highly regulated process.
      Numerous inducers of angiogenesis have been identified, including the members of
      the vascular endothelial growth factor family, angiopoietins, transforming growth
      factors, platelet-derived growth factor, tumor necrosis factor-alpha,
      interleukins and members of the fibroblast growth factor family. Vascular
      endothelial growth factor-A is the most potent pro-angiogenic protein described
      to date. It induces proliferation, sprouting and tube formation of endothelial
      cells. Angiogenesis is therefore a putative target for therapy. The potential
      application of different angiogenesis inhibitors is currently under intense
      clinical investigation. A better understanding of the biology of angiogenesis may
      reveal new targets for treating many diseases that are associated with this
      complex process. In this review, we summarize the most important molecular
      mechanisms mediating angiogenesis.

PMID- 17553710
TI  - The influence of pomegranate fruit extract in comparison to regular pomegranate
      juice and seed oil on nitric oxide and arterial function in obese Zucker rats.
AB  - Metabolic syndrome includes most widely distributed clinical conditions such as
      obesity, hypertension, dislipidemia, and diabetes. Pomegranate fruit extract
      (PFE), rich in polyphenolic antioxidants, reduces the expression of oxidation
      sensitive genes at the sites of perturbed shear-stress. The aim of this study was
      to evaluate the effect of PFE in comparison to regular pomegranate juice (PJ) and
      seed oil on the biological actions of nitric oxide (NO) and the arterial function
      in obese Zucker rats, a model of metabolic syndrome. Our results indicated that
      supplementation with PFE or PJ significantly decreased the expression of vascular
      inflammation markers, thrombospondin (TSP), and cytokine TGFbeta1 (P<0.05),
      whereas seed oil supplementation had a significant effect only on TSP-1
      expression (P <0.05). Plasma nitrate and nitrite (NO(x)) levels were
      significantly increased by PFE and PJ (P<0.05). Furthermore, the effect of PFE in
      increasing endothelial NO synthase (eNOS) expression was comparable to that of
      PJ. These data highlight possible clinical applications of PFE in metabolic
      syndrome.

PMID- 17553711
TI  - Real-time PCR assay in Leishmania-infected dogs treated with meglumine
      antimoniate and allopurinol.
AB  - A real-time PCR assay was exploited for monitoring the Leishmania DNA load in
      different tissues from 18 naturally-infected dogs before and after treatment with
      a combination of meglumine antimoniate (100mg/kg/day, subcutaneously) and
      allopurinol (10mg/kg/day, orally) for 30 days. After the combined therapy,
      allopurinol was continued at the same dose until the end of the observation
      period. Whole blood samples, lymph node aspirates, and skin biopsies were
      collected at the time of diagnosis, 1 month after starting therapy, and every 3
      months for 2 years. In six dogs parasite load assessments continued every 6
      months for a further 3 years. At each assessment, the dogs were examined for
      signs of disease and a clinical score was recorded. At diagnosis, the highest
      Leishmania DNA load was detected in lymph node aspirates. From 1-6 months post
      therapy a general improvement in clinical conditions was recorded in all dogs,
      which correlated with a decrease in the parasite DNA load in all tested tissues,
      even though it was less pronounced in lymph node aspirates. In the period from 9
      24 months post-therapy, a re-increase in parasite load was observed in the
      tissues of some dogs, concomitant with a disease relapse. The results show that
      the combined therapy with meglumine antimoniate and allopurinol promoted a
      clinical improvement which was accompanied by a reduction in the parasitic load
      in the blood, skin and lymph nodes but, even after long period of allopurinol
      administration alone, Leishmania may persist in dog tissues.

PMID- 17553712
TI  - Pain mechanisms and their implication for the management of pain in farm and
      companion animals.
AB  - Over the last two decades there has been a dramatic increase in the literature
      relating to the mechanisms and management of pain in domestic animals.
      Understanding the mechanisms of pain is crucial for its effective management.
      This review highlights the current understanding of the neurophysiology of
      nociception and the plastic changes involved in chronic pain states.
      Additionally, we describe a range of novel molecules and pathways that offer
      opportunities for the development of mechanism-based analgesic therapies. Pain
      management in animals is limited by pain assessment which remains highly
      subjective, with clinicians relying on indirect measures of pain, using rating
      scales and (less frequently) quantifiable physiological and behavioural
      parameters. The need for a systematic approach which would assess different pain
      components is well justified. Species-specific issues on pain assessment and
      management in mammalian companion and farm animals are addressed in the later
      part of this review.

PMID- 17553713
TI  - Central sensitization phenomena after third molar surgery: a quantitative sensory
      testing study.
AB  - BACKGROUND: Surgical removal of third molars may carry a risk of developing
      persistent orofacial pain, and central sensitization appears to play an important
      role in the transition from acute to chronic pain. AIM: The aim of this study was
      to investigate sensitization (primarily central sensitization) after orofacial
      trauma using quantitative sensory testing (QST). METHODS: A total of 32 healthy
      men (16 patients and 16 age-matched control subjects) underwent a battery of
      quantitative tests adapted to the trigeminal area at baseline and 2, 7, and 30
      days following surgical removal of a lower impacted third molar. RESULTS: Central
      sensitization for at least one week was indicated by significantly increased pain
      intensity evoked by intraoral repetitive pinprick and electrical stimulation
      (p<0.05) including facilitation of temporal summation mechanisms (p<0.05),
      extraoral repetitive electrical stimulation (p<0.001), significantly more
      frequent aftersensation in patients (p<0.001), extraoral hyperalgesia due to
      single pinprick stimulation (p<0.05) and larger pain areas due to intranasal
      stimulation (p<0.001). Peripheral sensitization was indicated by intraoral
      hyperalgesia due to single pinprick (p<0.05). CONCLUSION: We found clear signs of
      sensitization of the trigeminal nociceptive system for at least one week after
      the surgery. Our results indicate that even a minor orofacial surgical procedure
      may be sufficient to evoke signs of both central and peripheral sensitization,
      which may play a role in the transition from acute to chronic pain in susceptible
      individuals.

PMID- 17553714
TI  - Expression of c-Fos in the parabrachial nucleus following peripheral nerve injury
      in rats.
AB  - Chronic constriction injury (CCI) of the sciatic nerve in rats evokes c-Fos
      expression at spinal cord level. Using immunohistochemical methods we studied
      changes in c-Fos expression in the brain stem area, which is suggested as one of
      the major targets of projection neurons in the superficial dorsal horn laminae,
      i.e., the parabrachial area. During the first week following injury, the animals
      developed tactile allodynia. At this time we found an increase of c-Fos positive
      neurons in the parabrachial area, mainly in the pontine part where the group of c
      Fos immunoreactive neurons was present in the dorsal part of lateral parabrachial
      subnuclei. The number of c-Fos positive neurons gradually decreased up to 14 days
      following CCI. The specific activation of brain stem neurons during onset of
      mechanical allodynia could underlie the changes in central nociceptive processing
      following peripheral nerve injury.

PMID- 17553715
TI  - [3H] muscimol receptors sites in the carp (Cyprinus carpio L.) brain: binding
      assay and autoradiographic distribution.
AB  - Autoradiographic and binding techniques were used to study the presence of
      [(3)H]muscimol receptors sites in the carp brain. The radioligand was distributed
      with an high degree of anatomical selectivity. We found abundant labelling in the
      cerebellum, in the nucleus diffusus lobi inferioris, and in the torus
      longitudinalis. No labelling was detected within the epithalamus, thalamus and
      hypothalamus, while the telencephalon and the rhombencephalon displayed a low
      density of [(3)H]muscimol receptors sites. Binding assay showed the highest
      concentration of receptor sites in the nucleus diffusus lobi inferioris and the
      lowest in the medulla oblongata. Presence of [(3)H]muscimol binding sites within
      the visceral sensory area was noted. The rank order of displacement efficacy of
      unlabelled ligands observed, suggested that in brain membranes of carp the
      receptor binding of [(3)H]muscimol has the same pharmacological specificity
      previously reported in a large number of experiments with tissue homogenates. A
      general agreement in binding and autoradiography was observed. The present
      findings suggested that muscimol receptor could be involved in neuronal pathway
      controlling basic central actions like gustatory signal processing or spatial
      learning acquisition and retention.

PMID- 17553716
TI  - Capsaicin-induced avoidance behavior in the terrestrial Gastropoda Megalobulimus
      abbreviatus: evidence for TRPV-1 signaling and opioid modulation in response to
      chemical noxious stimuli.
AB  - The aim of this study was to measure the nociceptive response (avoidance latency)
      of the land snail Megalobulimus abbreviatus (N=8 in each group) after topical
      capsaicin exposure (0.1% and 0.5% in 20% ethanol) and to compare it to a well
      studied stressful (50 degrees C) thermal stimulus model. We also tested if
      ruthenium red, and capsazepine, respectively nonselective and selective TRPV1
      receptor antagonists, could modify both capsaicin- and thermal-evoked responses.
      Finally, animals were pretreated with morphine, naloxone or morphine plus
      naloxone prior to capsaicin stimuli. Latencies were measured when the animal
      lifted its head-foot complex 1 cm from the substrate. Data were compared using
      ANOVA and LSD post hoc, and the Student T Test (p<0.05). Capsaicin elicited dose
      dependent withdrawal behavior. The capsaicin vehicle (20% ethanol) also evoked a
      less intense but significant avoidance reaction. Capsazepine and ruthenium red
      attenuated both capsaicin and heat withdrawal responses, when compared to
      vehicles. Morphine increased, and naloxone, either alone or in combination with
      morphine, reduced capsaicin-evoked latencies when compared to morphine or saline.
      These results indicate that the TRPV1 receptor plays a role in the nociceptive
      circuits of M. abbreviatus.

PMID- 17553717
TI  - Acclimation effect on fatty acids of the coral Montipora digitata and its
      symbiotic algae.
AB  - Lipids play a key role in thermal and photo-acclimation processes, yet they are
      often neglected in stress studies. We investigated the influence of different
      light intensities and an increase of temperature on the fatty acid composition of
      the coral Montipora digitata and its symbiotic algae (i.e., zooxanthellae). Coral
      branches were subjected to 3 different light intensities (7, 30 and 95% sea
      surface photosynthetic active radiation) in filtered seawater for 35 days. Fatty
      acids as methyl esters were determined using gas chromatography (GC) and verified
      by GC-mass spectrometry. Different light intensities, but only in combination
      with increased temperature, significantly affected the fatty acid composition of
      the coral host and zooxanthellae. Temperature and light intensity increases
      caused reductions in the proportion of polyunsaturated fatty acids in both the
      host and symbionts. Most changes occurred in the host coral, which suggests that
      the host is more susceptible to environmental change than the symbiont, or that
      the host shields the symbionts from environmental change.

PMID- 17553718
TI  - cDNA cloning and mRNA expression of heat shock protein 90 gene in the haemocytes
      of Zhikong scallop Chlamys farreri.
AB  - Heat shock protein 90 (HSP90) is a highly conserved molecular chaperone
      contributing to the folding, maintenance of structural integrity and proper
      regulation of a subset of cytosolic proteins. The full-length cDNA of Zhikong
      scallop Chlamys farreri HSP90 (designated CfHSP90) was cloned by EST and rapid
      RACE techniques. It was of 2710 bp, including an open reading frame (ORF) of 2181
      bp encoding a polypeptide of 726 amino acids with all the five HSP90 family
      signatures. BLAST analysis revealed that the CfHSP90 gene shared high similarity
      with other known HSP90 genes. Fluorescent real-time quantitative RT-PCR was used
      to examine the expression pattern of CfHSP90 mRNA in haemocytes of scallops
      exposed to Cd2+, Pb2+ and Cu2+ for 10 and 20 days, respectively. All the three
      heavy metals could induce CfHSP90 expression. There was a clear dose-dependent
      expression pattern of CfHSP90 after heavy metals exposure for 10 days or 20 days.
      Different concentrations of the same metal resulted in different effects on
      CfHSP90 expression. The results indicated that CfHSP90 responded to various heavy
      metal stresses with a dose-dependent expression pattern as well as exposure time
      effect, and could be used as a molecular biomarker in a heavy metal polluted
      environment.

PMID- 17553719
TI  - Inducible nitric oxide synthase and histopathological correlation in chronic
      viral hepatitis.
AB  - BACKGROUND: Chronic liver disorders represent a serious health problem. Nitric
      oxide (NO) synthesized by inducible nitric oxide synthase (iNOS) can function as
      an antimicrobial agent able to kill or reduce replication of microorganisms, and
      plays an important role in immune regulation. This study was undertaken to
      evaluate the expression of iNOS in chronic viral hepatitis and its relation to
      histopathology. METHODS: This study included 56 patients with chronic viral
      hepatitis (38 hepatitis B, 18 hepatitis C). There were 35 men and 21 women with a
      mean age of 38.6+/-21.731 years. A modified form of the histology activity index
      (HAI) designed by Ishak and colleagues was used to assess grading and staging of
      chronic viral hepatitis. The needle biopsy specimens were fixed in 10% formalin
      and routinely processed. Routine hematoxylin-eosin, periodic acid-Schiff, and
      reticulin staining, and iNOS immunoperoxidase technique were performed on
      paraffin-embedded tissues. RESULTS: We demonstrated that all liver samples had a
      marked iNOS expression, with a diffuse distribution pattern. iNOS consistently
      labeled mononuclear cells infiltrating portal tracts in all samples. Statistical
      evaluation of data showed that the iNOS expression correlated with the HAI and
      fibrosis. Furthermore a correlation between iNOS and severity of disease was
      detected (r=0.772, p=0.000). CONCLUSIONS: Further investigations are required to
      determine whether iNOS-related treatment protocols could be useful in reducing
      disease severity.

PMID- 17553720
TI  - Sources of endogenous glucose production in the Goto-Kakizaki diabetic rat.
AB  - Plasma glucose, insulin and glucose tolerance were quantified in diabetic Goto
      Kakizaki (GK) rats (342+/-45 g, n = 5) and compared with weight-matched non
      diabetic Wistars (307+/-30 g, n = 8). Compared to Wistars, GK rats had higher
      fasting plasma insulin (219+/-50 versus 44+/-14 pmol/l, P<0.002) and glucose
      (9.2+/-2.3 versus 5.5+/-0.5 mmol/l, P<0.025). GK rats showed impaired glucose
      tolerance (IPGTT 2 h plasma glucose=14+/-1.5 versus 6.4+/-0.1 mmol/l, P<0.001).
      Endogenous glucose production (EGP) from glycogenolysis, phosphoenolpyruvate
      (PEP) and glycerol after 6 hours of fasting was quantified by a primed infusion
      of [U-(13)C]glucose and (2)H(2)O tracers and (2)H/(13)C NMR analysis of plasma
      glucose. EGP was higher in GK compared to Wistar rats (191+/-16 versus 104+/-27
      mumol/kg per min, P<0.005). This was sustained by increased gluconeogenesis from
      PEP (85+/-12 versus 35+/-4 mumol/kg per min, P<0.02). Gluconeogenesis from
      glycerol was not different (20+/-3 in Wistar versus 30+/-6 mumol/kg per min for
      GK), and glycogenolysis fluxes were also not significantly different (76+/-23
      mumol/kg per min for GK versus 52+/-19 mumol/kg per min for Wistar). The Cori
      cycle accounted for most of PEP gluconeogenesis in both Wistar and GK rats (85+/
      15% and 77+/-10%, respectively). Therefore, increased gluconeogenesis in GK rats
      is largely sustained by increased Cori cycling while the maintenance of
      glycogenolysis indicates a failure in hepatic autoregulation of EGP.

PMID- 17553721
TI  - Replication-deficient mutant Herpes Simplex Virus-1 targets professional antigen
      presenting cells and induces efficient CD4+ T helper responses.
AB  - Both neutralizing antibodies and cytotoxic T-cells are necessary to control a
      viral infection. However, vigorous T helper responses are essential for their
      elicitation and maintenance. Here we show that a recombinant replication
      deficient Herpes Simplex Virus (HSV)-1 vector encoding the Human Immunodeficiency
      Virus (HIV)-1 matrix protein p17 (T0-p17) was capable of infecting professional
      antigen presenting cells (APCs) in vitro and in vivo. The injection of T0-p17 in
      the mouse dermis generated a strong p17-specific CD4+ T helper response preceding
      both p17-specific humoral and effector T cell responses. Moreover, we show that
      T0-p17 infection did not interfere with the endogenous processing of the
      transgene encoded antigen, since infected APCs were able to evoke a strong recall
      response in vitro. Our results demonstrate that replication-deficient HSV vectors
      can be appealing candidates for the development of vaccines able to trigger T
      helper responses.

PMID- 17553722
TI  - [Elective cesarean section for all twin pregnancies: logical step or dangerous
      turn?].

PMID- 17553724
TI  - Experimental measurement and modeling analysis on mechanical properties of tensor
      tympani tendon.
AB  - In this paper, we report mechanical properties of the tensor tympani tendon of
      human ear measured from uniaxial tensile, stress relaxation and failure tests.
      The hyperelastic Ogden model and digital image correlation method were employed
      to analyze experimental data. The constitutive equation of the tendon was derived
      through data iteration processes, and Young's modulus was presented as a function
      of stress. The viscoelastic property of the tendon was described by stress
      relaxation function and hysteresis. Furthermore, three-dimensional finite element
      analysis was carried out on five tendon models to investigate relationship
      between the structure and properties. The dimensions of the tendon were also
      measured by image processing techniques and presented with statistic
      significance. The structure and properties of the tensor tympani tendon reported
      in this study add new data into the study of ear tissue biomechanics.

PMID- 17553725
TI  - Evaluation of cartilage defects with near-infrared spectroscopy (NIR): an ex vivo
      study.
AB  - Damaged cartilage undergoes complex changes in composition, histological
      structure, and mechanical properties. Near-infrared-spectroscopy (NIR
      spectroscopy) is an important method to measure changes in composition of complex
      composites. The present study was aimed at evaluating NIR spectroscopy as a means
      to quantitate tissue alterations in low grade cartilage defects. Fresh medial
      femoral condyles from female sheep were collected. Cartilage defects were graded
      according to the International Cartilage Repair Society (ICRS). Specimens were
      examined by a NIR spectroscopy device (spectral range of 1100-1700 nm).
      Absorption spectra were calculated from the reference and measurement spectra. As
      indicator for cartilage composition the ratio (absorption ratio, AR) of the two
      main absorption bands in this region was calculated. Mechanical stiffness was
      measured as Shore A. Water-, glycosaminoglycan-, and collagen content and
      histological grade (Mankin score) were determined. The NIR absorption in ICRS
      grade 1 defects (AR=2.1+/-0.1) was significantly higher than in intact cartilage
      (AR=1.5+/-0.1). ICRS grade 2 specimens tended to a higher NIR absorption. NIR
      absorption correlated significantly with Mankin score (R=0.896), water content
      (R=0.845), and mechanical stiffness (R=0.877). Initial cartilage degeneration
      correlates with changes in NIR absorption, indicating NIR spectroscopy to reflect
      complex structural changes in degenerated cartilage. The data suggest that NIR
      spectroscopy could be useful for in situ detection of early cartilage defects.

PMID- 17553726
TI  - Calibration of an instrumented treatment table for measuring manual therapy
      forces applied to the cervical spine.
AB  - Manual therapy techniques are commonly used to treat musculoskeletal neck
      disorders, but little is known about the manual forces applied during cervical
      spine treatment. Forces may vary between practitioners, and this may affect
      patient outcomes. This study reports the development of an instrumented treatment
      table and its calibration for measuring posteroanterior-directed forces applied
      during cervical spine mobilisation. A treatment table surface was instrumented
      with seven biaxial load cells to measure manually applied forces in three planes.
      Accuracy of the system was evaluated using known weights (unloaded and loaded to
      represent a patient's body weight), selected to be consistent with the level of
      forces expected to be applied during cervical mobilisation. Recorded force values
      strongly correlated with known weights (Pearson's r=0.999 to 1.000 for forces
      applied in different directions and locations, unloaded and loaded). The accuracy
      of forces in the unloaded condition was very good for vertical forces (mean
      absolute error 1.1N, SD 1.5), and reasonably good for horizontal forces (2.8N, SD
      2.4 for mediolateral, 3.4N, SD 1.5 for caudad-cephalad). In the loaded condition
      absolute error increased slightly for horizontal forces. The accuracy of measured
      forces indicates the instrumented table is acceptable for measuring cervical
      mobilisation forces. Using it allows practitioners to perform manual techniques
      using their usual clinical technique, however interpretation of force data is
      limited because it represents force applied to the table rather than at a
      specific joint.

PMID- 17553727
TI  - The influence of neck pain on balance and gait parameters in community-dwelling
      elders.
AB  - Neck pain has been shown to be associated with balance disturbances. Balance and
      gait speed are also known to decline with ageing. The aim of this study was to
      determine whether the presence of neck pain was associated with a decline in
      postural stability and gait speed over and above what is expected with normal
      ageing. Twenty female subjects with idiopathic neck pain and 20 healthy female
      controls aged between 65 and 82 years were studied. Subjects performed balance
      tests on a computerised force plate under conditions of eyes open, eyes closed on
      firm and soft surfaces in comfortable and narrow stance. Sway energy and root
      mean square (RMS) amplitude of sway were measured. Subjects also undertook a
      Timed Ten Metre Walk Test, with and without head turning. There were trends for
      the elderly group with neck pain to have poorer balance than the healthy controls
      across most balance conditions, although differences were significant only in the
      following tests; comfortable stance--eyes closed on a firm surface (p=0.02), eyes
      open on a soft surface (p=0.01); narrow stance--eyes open on a firm surface
      (p=0.02). In the Timed Ten meter Walk Test, elderly subjects with neck pain had a
      slower self-selected gait speed (p=0.02) and cadence (p=0.04) in the head turn
      condition, as well as a longer gait cycle duration both with (p=0.00) and without
      head turns (p=0.04). The results of this study suggest that neck pain in the
      elderly may contribute to some disturbance in balance and gait parameters over
      and above that which occurs with normal ageing.

PMID- 17553728
TI  - Effects of slouching and muscle contraction on the strain of the iliolumbar
      ligament.
AB  - The study consisted of biomechanical modelling and in vitro experiments. The
      objective of the study was to find a mechanical cause of acute low back pain
      (LBP) in everyday situations. The precise mechanism producing LBP is still under
      discussion. Most biomechanical studies link the concepts of stooped postures and
      buckling instability of the spine under high compressive load. No biomechanical
      model addresses situations with small or neglectable compressive spinal load. The
      proposed conceptual model describes strain on the iliolumbar ligaments (ILs) when
      slouching from standing upright. Delayed or absent recruitment of back muscles
      that protect against hyperkyphosis of the lumbar spine is a conditional factor.
      Erector spinae and multifidus muscle forces are included, representing a
      bifurcation in back muscle force: one part acting on the iliac bones and one part
      acting on the sacrum. The multifidus muscle action on the sacrum may produce
      nutation which can be counteracted by pelvic floor muscles, which would link back
      problems and pelvic floor problems. The effect of simulated muscle tension on the
      ILs and the L5-S1 intervertebral disc angle was measured using embalmed
      specimens. Forces were applied to simulate erector spinae and sacral part of
      multifidus tension, bilateral up to 100 N each. Strain gauge sensors registered
      elongation of the ILs. Explorative biomechanical model calculations show that
      dynamic slouching, driven by upper body weight and (as an example) rectus
      abdominis muscle force may produce failure load of the spinal column and the ILs.
      The quasi-static test on embalmed specimens showed a significant increase of IL
      elongation with simulated rectus abdominis muscle force. Adding erector spinae or
      multifidus muscle tension eased the ILs. Sudden slouching of the upright trunk
      may create failure risk for the spine and ILs. This loading mode may be prevented
      by controlling loss of lumbar lordosis with erector spinae and multifidus muscle
      force.

PMID- 17553729
TI  - Vitamin E attenuates cold-induced rat liver oxidative damage reducing H2O2
      mitochondrial release.
AB  - Vitamin E is a major chain-breaking antioxidant which is able to reduce liver
      oxidative damage without modifying aerobic capacity in T(3)-treated rats. We
      investigated whether vitamin E has similar effects in hyperthyroid state induced
      by cold exposure. Cold exposure increased aerobic capacity and O(2) consumption
      in homogenates and mitochondria and tissue mitochondrial protein content. Vitamin
      E did not modify aerobic capacity and mitochondrial protein content of cold
      liver, but increased ADP-stimulated respiration of liver preparations. Succinate
      supported H(2)O(2) release rates were increased by cold during basal and
      stimulated respiration, whereas the pyruvate/malate-supported ones increased only
      during basal respiration. Vitamin administration to cold-exposed rats decreased
      H(2)O(2) release rates with both substrates during basal respiration. This effect
      reduced ROS flow from mitochondria to cytosol, limiting liver oxidative damage.
      Cold exposure also increased mitochondrial capacity to remove H(2)O(2), which was
      reduced by vitamin treatment, showing that the antioxidant also lowers H(2)O(2)
      production rate. The different effects of cold exposure and vitamin treatment on
      H(2)O(2) generation were also found in the presence of respiration inhibitors.
      Although this can suggest that the cold and vitamin induce opposite changes in
      mitochondrial content of autoxidizable electron carriers, it is likely that
      vitamin effect is due to its capacity to scavenge superoxide radical. Finally,
      vitamin E reduced mitochondrial oxidative damage and susceptibility to oxidants,
      and prevented Ca(2+)-induced swelling elicited by cold. In the whole, our results
      suggest that vitamin E is able to maintain aerobic capacity and attenuate
      oxidative stress of hepatic tissue in cold-exposed rats modifying mitochondrial
      population characteristics.

PMID- 17553730
TI  - Neurocognitive mechanisms of anxiety: an integrative account.
AB  - Anxiety can be hugely disruptive to everyday life. Anxious individuals show
      increased attentional capture by potential signs of danger, and interpret
      expressions, comments and events in a negative manner. These cognitive biases
      have been widely explored in human anxiety research. By contrast, animal models
      have focused upon the mechanisms underlying acquisition and extinction of
      conditioned fear, guiding exposure-based therapies for anxiety disorders. Recent
      neuroimaging studies of conditioned fear, attention to threat and interpretation
      of emotionally ambiguous stimuli indicate common amygdala-prefrontal circuitry
      underlying these processes, and suggest that the balance of activity within this
      circuitry is altered in anxiety, creating a bias towards threat-related
      responses. This provides a focus for future translational research, and targeted
      pharmacological and cognitive interventions.

PMID- 17553731
TI  - Combinatorial biosynthesis for drug development.
AB  - Combinatorial biosynthesis can refer to any strategy for the genetic engineering
      of natural product biosynthesis to obtain new molecules, including the use of
      genetics for medicinal chemistry. However, it also implies the possibility that
      large libraries of complex compounds might be produced to feed a modern high
      throughput screening operation. This review focuses on the multi-modular enzymes
      that produce polyketides, nonribosomal peptides, and hybrid polyketide-peptide
      compounds, which are the enzymes that appear to be most amenable to truly
      combinatorial approaches. The recent establishment of a high-throughput strategy
      for testing the activity of many non-natural combinations of modules from these
      enzymes should help speed the advance of this technology.

PMID- 17553732
TI  - They've got a ticket to ride: Xenorhabdus nematophila-Steinernema carpocapsae
      symbiosis.
AB  - The association between the bacterium Xenorhabdus nematophila and the nematode
      Steinernema carpocapsae is emerging as a model system to understand mutually
      beneficial symbioses. X. nematophila, but not other Xenorhabdus species, colonize
      a discrete region of a specific developmental stage of S. carpocapsae nematodes.
      Recent progress has led to the identification of bacterial genes necessary for
      colonization. Furthermore, new details have been elucidated regarding the
      morphology and physiology of the colonization site and the bacteria within it. A
      deeper understanding of the molecular mechanisms underlying the association of X.
      nematophila will undoubtedly yield insights into fundamental processes underlying
      the ubiquitous association of microbes with animals.

PMID- 17553733
TI  - Identification of bacterial small non-coding RNAs: experimental approaches.
AB  - Almost 140 bacterial small RNAs (sRNAs; sometimes referred to as non-coding RNAs)
      have been discovered in the past six years. The majority of these sRNAs were
      discovered in Escherichia coli, and a smaller subset was characterized in other
      bacteria, many of which were pathogenic. Many of these genes were identified as a
      result of systematic screens using computational prediction of sRNAs and
      experimental-based approaches, including microarray and shotgun cloning. A
      smaller number of sRNAs were discovered by direct labeling or by functional
      genetic screens. Many of the discovered genes, ranging in size from 50 to 500
      nucleotides, are conserved and located in intergenic regions, in-between open
      reading frames. The expression of many of these genes is growth phase dependent
      or stress related. As each search employed specific parameters, this led to the
      identification of genes with distinct characteristics. Consequently, unique sRNAs
      such as those that are species-specific, sRNA genes that are transcribed under
      unique conditions or genes located on the antisense strand of protein-encoding
      genes, were probably missed.

PMID- 17553734
TI  - From the deep sea to the stars: human life support through minimal communities.
AB  - Support of human life during long-distance exploratory space travel or in the
      creation of human habitats in extreme environments can be accomplished using the
      action of microbial consortia inhabiting interconnected bioreactors, designed for
      the purpose of reconversion of solid, liquid and gaseous wastes produced by the
      human crew or by one of the compartments of the bioregenerative loop, into
      nutritional biomass, oxygen and potable water. The microorganisms responsible for
      bioregenerative life support are part of Earth's own geomicrobial reconversion
      cycle. Depending on the resources and conditions available, minimal life support
      systems can be assembled using appropriately selected microorganisms that possess
      metabolic routes for each specific purpose in the transformation cycle. Under
      control of an engineered system, a reliable life-support system can hence be
      provided for.

PMID- 17553735
TI  - Raman mapping of coesite inclusions in garnet from the Kokchetav Massif (Northern
      Kazakhstan).
AB  - Coesite inclusions occur in a wide range of lithologies and coesite is therefore
      a powerful ultrahigh-pressure (UHP) indicator. The transformation of coesite to
      quartz is evidenced by three optically well identifiable characteristics (e.g.
      palisade textures, radial crack patterns, polycrystalline quartz pseudomorphs).
      Under overpressure monomineralic coesite (on an optical basis), lacking the above
      transformation characteristics may survive. Raman micro-spectroscopy was applied
      on monomineralic coesite inclusions in garnet porphyroblasts from diamond-bearing
      garnet-clinozoisite-biotite gneisses of the Barchi-Kol area (Kokchetav Massif,
      Northern Kazakhstan). These coesite inclusions are euhedral and display a
      characteristic anisotropic hallo. However, Raman maps and separate spectra of
      these inclusions display shifted bands for coesite and quartz. Microscopically
      undetectable, quartz shows on the Raman map as a thin shell around coesite
      inclusion. Shift of the main coesite band allows to estimate their overpressure:
      coesite inclusions record 0-2.4 GPa in garnet and zircon. The quartz shell
      remains under lower pressure 0-1.6 GPa. The possible application of coesite and
      quartz Raman geobarometers for UHP metamorphic rocks is discussed.

PMID- 17553736
TI  - Structure and vibrational frequencies of 1-naphthaldehyde based on density
      functional theory calculations.
AB  - The mid and far FTIR and Raman spectra were measured in the liquid state. The
      fundamental vibrational frequencies and intensity of vibrational bands were
      evaluated using density functional theory (DFT) and standard B3LYP/6-311+G**
      basis set combination. The vibrational spectra were interpreted, with the aid of
      normal coordinate analysis based on a scaled quantum mechanical (SQM) force
      field. The infrared and Raman spectra were also predicted from the calculated
      intensities. Comparison of simulated spectra with the experimental spectra
      provides important information about the ability of the computational method to
      describe the vibrational modes. Unambiguous vibrational assignment of all the
      fundamentals was made using the total energy distribution (TED).

PMID- 17553737
TI  - Synthesis, spectral studies and antibacterial activity of novel macrocyclic
      Co(II) compounds.
AB  - Ten novel macrocyclic Co(II) compounds have been synthesized by treating four
      N(4) and six N(2)O(2) donor macrocycles with cobalt chloride in methanol. These
      compounds were characterized by elemental, IR, (1)H, (13)C NMR, mass, electronic
      spectral analysis, molar conductance and magnetic susceptibility measurements.
      Thermal behavior of these compounds has been studied by the thermogravimetric
      analysis. An octahedral geometry has been proposed for all of these complexes.
      All the macrocycles and macrocyclic Co(II) compounds along with existing
      antibacterial drugs were screened for antibacterial activity against Gram +ve and
      Gram -ve bacteria. All these compounds were found to be more active when compared
      to streptomycin and ampicillin.

PMID- 17553738
TI  - DFT and ab initio study of structure of dyes derived from 2-hydroxy and 2,4
      dihydroxy benzoic acids.
AB  - We present a detailed analysis of the structural, infrared spectra and visible
      spectra of a series of azo dyes preparation of salicylic acid and 2,4-dihydroxy
      benzoic acid derivatives as the coupling component. The preparation of these azo
      dyes with salicylic acid and 2,4-dihydroxy benzoic acid derivatives (salicylic
      acid, methyl salicylate, ethyl salicylate, butyl salicylate, methyl 2,4-dihydroxy
      benzoate, ethyl 2,4-dihydroxy benzoate, salicylaldehyde, salicylamide, 2,4
      dihydroxy benzamide, salicylaldoxime) have been investigated theoretically by
      performing HF and DFT levels of theory using the standard 6-31G* basis set. The
      optimized geometries and calculated vibrational frequencies are evaluated via
      comparison with experimental values. The vibrational spectral data obtained from
      solid phase FT-IR spectra are assigned modes based on the results of the
      theoretical calculations. The observed spectra are found to be in good agreement
      with the calculations.

PMID- 17553739
TI  - Spectrophotometric determination of some histamine H1-antagonists drugs in their
      pharmaceutical preparations.
AB  - Two rapid, simple and sensitive extractive specrophotometric methods has been
      developed for the determination of three histamine H1-antagonists drugs, e.g.,
      chlorphenoxamine hydrochloride (CPX), diphenhydramine hydrochloride (DPH) and
      clemastine (CMT) in bulk and in their pharmaceutical formulations. The first
      method depend upon the reaction of molybdenum(V) thiocyanate ions (Method A) with
      the cited drugs to form stable ion-pair complexes which extractable with
      methylene chloride, the orange red color complex was determined colorimetrically
      at lambda(max) 470nm. The second method is based on the formation of an ion
      association complex with alizarin red S as chromogenic reagents in acidic medium
      (Method B), which is extracted into chloroform. The complexes have a maximum
      absorbance at 425 and 426nm for (DPH or CMT) and CPX, respectively. Regression
      analysis of Beer-Lambert plots showed a good correlation in the concentration
      ranges of 5.0-40 and 5-70microgmL(-1) for molybdenum(V) thiocyanate (Method A)
      and alizarin red S (Method B), respectively. For more accurate analysis, Ringbom
      optimum concentration ranges were calculated. The molar absorptivity, Sandell
      sensitivity, detection and quantification limits were calculated. Applications of
      the procedure to the analysis of various pharmaceutical preparations gave
      reproducible and accurate results. Further, the validity of the procedure was
      confirmed by applying the standard addition technique and the results obtained in
      good agreement well with those obtained by the official method.

PMID- 17553740
TI  - Development and evaluation of SYBR Green I-based one-step real-time RT-PCR assay
      for detection and quantification of Chikungunya virus.
AB  - The development of a one-step SYBR Green I-based real-time RT-PCR assay is
      reported for detection and quantification of Chikungunya virus (CHIKV) in acute
      phase patient serum samples by targeting the E1 structural gene. A linear
      relationship was obtained between the virus concentration and cycle threshold
      (C(t)) value over a range of 10(7)-0.1PFU/ml. The reported assay was found to be
      10-fold more sensitive compared to conventional RT-PCR with a detection limit of
      0.1PFU/ml. The feasibility of this reported assay system for clinical diagnosis
      was validated with 51 suspected acute-phase serum samples of the recent CHIKV
      epidemic in southern India, 2006. The comparative evaluation with acute-phase
      patient serum samples revealed the higher sensitivity of real-time RT-PCR assay
      by picking up six additional samples with low copy number of template. None of
      the healthy serum samples analyzed in this study showed amplification. The
      quantification of the viral load in the acute-phase serum samples was also
      determined employing the standard curve, which varies from 0.1 to 10(7)PFU/ml.
      These findings demonstrated that the reported assay has the potential usefulness
      for clinical diagnosis due to simultaneous detection and quantification of
      Chikungunya virus in acute-phase patient serum samples.

PMID- 17553741
TI  - Rifampicin-induced CYP3A4 activation in CTX patients cannot replace
      chenodeoxycholic acid treatment.
AB  - Cerebrotendinous xanthomatosis (CTX) is a rare neurodegenerative disorder with
      cholestanol accumulation resulting from mutations in the sterol 27-hydroxylase
      gene (CYP27A). Conventional treatment includes chenodeoxycholic acid and HMG-CoA
      reductase inhibitors. Mice with disrupted Cyp27A (Cyp27 KO) do not show elevated
      cholestanol levels nor develop CTX manifestations. This phenomenon was proposed
      to be due to murine CYP3A overexpression leading to an alternative pathway for
      degradation of bile alcohols including cholestanol. Our objective was to examine
      the influence of CYP3A4 induction on cholestanol elimination in CTX patients.
      Rifampicin (600 mg/day x 7 days), known to induce the PXR, and thereby to
      increase CYP3A activity, was used. The degree of CYP3A4 induction was assessed by
      comparing midazolam pharmacokinetics before and after rifampicin treatment.
      Cholestanol levels and cholestanol/cholesterol ratios were assayed during the
      experimental period and compared to a 3 weeks period without treatment. The
      results show that despite 60% increase in CYP3A4 activity following rifampicin
      treatment, there is no significant change in cholestanol levels. We conclude that
      up-regulated expression of CYP3A affects cholestanol elimination in mice
      differently as compared to its effect in CTX patients. Therefore, CYP3A4 inducers
      cannot replace chenodeoxycholic acid for the treatment of CTX.

PMID- 17553742
TI  - Some peculiarities of time-frequency dynamics of spike-wave discharges in humans
      and rats.
AB  - OBJECTIVE: Time-frequency dynamics of spike-wave discharges (SWDs) were
      investigated in patients with absence seizures and in WAG/Rij rats, a genetic
      model of absence epilepsy using a specially developed wavelet transform. METHODS:
      Two types of SWDs were analyzed in both species: the most frequently occurring
      discharges (of minimal 3.6-4.0 s or more) and shorter ones recorded from various
      cortical regions. RESULTS: The more prolonged discharges had two phases: during
      the initial part (from tenth of seconds to 1 s) of the seizure the frequency
      decreased quickly from 5 to 3.5 Hz in patients and from about 15 to 10 Hz in
      rats. A slower frequency decrease with periodical fluctuations was observed in
      both species during the second part of the discharge: the frequency decreased
      towards the end of the discharge to 3 Hz in patients and to 6-7 Hz in rats. The
      frequency of the short discharges decreased fast during the whole discharge: from
      5 to 2-2.5 Hz and from about 15 to 5 Hz in patients and rats, respectively.
      CONCLUSIONS: Comparison of data obtained in patients with typical absence
      epilepsy and WAG/Rij rats with genetic absence epilepsy revealed that the time
      frequency dynamics of SWDs had similar properties but in a different frequency
      range. SIGNIFICANCE: The study of time-frequency dynamics using this specially
      developed wavelet transform revealed two different types of SWDs, which most
      likely represent different dynamics in the cortico-thalamo-cortical loop during
      shorter and more prolonged discharges.

PMID- 17553743
TI  - Efficacy of rotigotine transdermal system in severe restless legs syndrome: a
      randomized, double-blind, placebo-controlled, six-week dose-finding trial in
      Europe.
AB  - BACKGROUND: In a pilot placebo-controlled study, low dosages of 0.5-2mg/24h
      rotigotine showed a dose-dependent beneficial effect in restless legs syndrome
      (RLS) patients. METHODS: Efficacy and safety of the dopamine agonist rotigotine,
      formulated as a once-daily transdermal system (patch), was investigated for five
      fixed dosages and compared to placebo in patients with idiopathic RLS in a double
      blind, randomized, parallel-group, multicenter, six-week dose-finding trial.
      Primary efficacy measure was the total score of the International RLS Severity
      Scale (IRLS); in addition, the RLS-6 scales and the Clinical Global Impressions
      (CGI) were administered. RESULTS: Of 371 enrolled patients, 341 patients (mean
      age 58+/-10years, 67% females) were randomized. The IRLS total score improved
      between baseline and end of the six-week treatment period by -10.6 (0.5mg/24h
      rotigotine; patch area 2.5cm2), -15.1 (1mg/24h; 5cm2), -15.7 (2mg/24h; 10cm2), 
      17.5 (3mg/24h; 15cm2), and -14.8 (4mg/24h, 20cm2) as compared to placebo (-9.2).
      The hierarchical statistical test procedure demonstrated superiority of
      rotigotine over placebo for 4mg/24h, 3mg/24h, 2mg/24h, and 1mg/24h, with p-values
      of 0.0013, <0.0001, 0.0003, and 0.0004, respectively. Only the 0.5mg/24h dose was
      not different compared to placebo (p=0.2338). The CGI and the RLS-6 severity
      items supported the efficacy of the rotigotine doses beyond 0.5mg/24h. The most
      frequent side effects were application site reactions and nausea and tended to be
      more frequent with higher doses. CONCLUSIONS: This dose-finding trial identified
      the range for a maintenance dose of rotigotine from 1mg/24h to 3mg/24h. The
      lowest dose was ineffective and, with the highest dose, no additional benefit was
      observed.

PMID- 17553744
TI  - Heat-related injuries resulting in hospitalisation in Australian sport.
AB  - The aim of this study was to summarise the extent and characteristics of cases of
      illness due to environmental heat, significant enough to result in
      hospitalisation, and arising during sporting activity in Australia. Cases were
      identified from the hospital separations database compiled by the Australian
      Institute of Health and Welfare, using the allocated external cause and diagnosis
      codes and the activity code "While engaged in sports". Hospital separations for
      the 2 years 2002-2003 and 2003-2004 were used. One hundred and forty eight cases
      were identified (68% male). Cases were fairly evenly distributed across 10-year
      age groups starting from age 15 years, apart from fewer cases between 55 and 64
      years. Nearly two thirds of the cases occurred in the summer months (December to
      February inclusive). The most commonly involved individual sports were lawn
      bowls, cricket, softball, golf, marathon running and walking, and the rate was
      highest for triathlons, lawn bowls, cricket, and running. Rates for persons aged
      65 years or older were more than twice the rates at younger ages. Heat-related
      disorders are an uncommon cause of significant morbidity in Australians
      participating in sporting activity. However, particular sports have a relatively
      high rate of occurrence and these sports would provide an appropriate focus for
      prevention activity. The availability of a specific code in the International
      Classification of Diseases and Injuries to cover excessive endogenous production
      of heat would assist future analyses of the role of thermoregulatory disturbance
      in leading to morbidity in persons participating in sporting activity.

PMID- 17553745
TI  - Influence of exercise mode and maximal lactate-steady-state concentration on the
      validity of OBLA to predict maximal lactate-steady-state in active individuals.
AB  - The aim of this study was to analyze the effects of exercise mode on the validity
      of onset of blood lactate accumulation (OBLA-3.5-mM fixed blood lactate
      concentration) to predict the work-rate at maximal lactate steady state
      (MLSS(work-rate)). Eleven recreationally active males (21.3+/-2.9 years, 72.8+/
      6.7kg, 1.78+/-0.1m) performed randomly incremental tests to determine OBLA (stage
      duration of 3min), and 2 to 4 constants work-rate exercise tests to directly
      determine maximal lactate steady state parameters on a cycle-ergometer and
      treadmill. For both exercise modes, the OBLA was significantly correlated to
      MLSS(work-rate), (cycling: r=0.81 p=0.002; running: r=0.94, p<0.001). OBLA
      (156.2+/-41.3W) was lower than MLSS(work-rate) (179.6+/-26.4W) during cycling
      exercise (p=0.007). However, for running exercise, there was no difference
      between OBLA (3.2+/-0.6ms(-1)) and MLSS(work-rate) (3.1+/-0.4ms(-1)). The
      difference between OBLA and MLSS(work-rate) on the cycle-ergometer (r=0.86;
      p<0.001) and treadmill (r=0.64; p=0.048) was significantly related to the
      specific MLSS. We can conclude that the validity of OBLA on predicting MLSS(work
      rate) is dependent on exercise mode and that its disagreement is related to
      individual variations in MLSS.

PMID- 17553746
TI  - Cardiac rupture in embolic myocardial infarction after implantation of a valved
      aortic conduit.
AB  - We report a case of an apical myocardial infarction complicated by left
      ventricular wall rupture due to coronary artery embolism four years after surgery
      of an acute type A dissection of an aortic aneurysm with implantation of a valved
      aortic conduit.

PMID- 17553747
TI  - A randomised study of three different informational AIDS prior to coronary
      angiography, measuring patient recall, satisfaction and anxiety.
AB  - BACKGROUND: Informed consent is a basic standard of care for all patients
      undergoing medical procedures, but recall of information has been shown to be
      poor. We sought to compare verbal, written and animated audiovisual information
      delivery, during consent for coronary angiography, by measuring improvement in
      recall. METHOD: A sample population of 99 cardiac patients at Flinders Medical
      Centre was randomised (1:1:1) to receive one of three information delivery
      methods. The information content was standardised by a risk proforma, which
      explained the procedure and defined 12 specific risks. Recall, satisfaction and
      anxiety were assessed by a questionnaire administered at three different time
      points: post-consent, post-procedure and at 30 days. Effect of delivery method on
      satisfaction and anxiety was rated on a self-reported scale from 1-5, with 5
      representing very satisfied or very anxious. Groups were compared by non
      parametric testing and a p-value of <0.05 was considered statistically
      significant. RESULTS: Patients were a median age of 64 (i.q.r. 56, 72) years.
      Information delivery method had no effect on recall of risks at any time-point
      (p=0.2, 0.7, 0.5, respectively) and the average recall score across the
      population was 3-4 out of 12. There was no significant effect on median
      satisfaction scores: verbal; 5 (i.q.r.4, 5) versus written/audiovisual; 4
      (i.q.r.4, 5) (p=ns), or on median anxiety scores: verbal; 3 (i.q.r.2, 4) versus
      written/audiovisual; 3 (i.q.r.2, 4) (p=ns). CONCLUSION: Despite careful design of
      an innovative audiovisual delivery technique aimed at optimising comprehension
      and aiding memory, recall of information was poor and informational aids showed
      no improvement. Modes of information delivery are not the key to patient
      assimilation of complex medical information.

PMID- 17553749
TI  - Age- and sex-specific nociceptive response to endothelin-1.
AB  - Endothelin-1 (ET-1) is a chemical mediator released by the body at sites of
      injury and disease. This study tests the hypothesis that ET-1-induced nociception
      changes with age and sex. Intraplantar ET-1 (1.1 and 3.3 nmol) produced age
      specific paw flinching and licking (postnatal day 7 > 21 > 60). The onset and
      duration of the nociceptive responses was dependent on age. Postnatal day (P) 21
      and 60 rats displayed an immediate onset of behavior that subsided with time,
      whereas the P7 rats had a delayed behavioral response that onset at 20 minutes
      after ET-1 administration and continued beyond the 75 minute observation period.
      P7 males showed greater paw flinching compared with females. In addition to
      spontaneous nociceptive behaviors, ET-1 produced mechanical allodynia in all
      ages. As with spontaneous nociception, ET-1-induced mechanical allodynia was of a
      longer duration in the younger aged rats compared with adult rats. These findings
      show that ET-1 produces both spontaneous nociceptive behaviors and evoked
      mechanical allodynia in both young and adult rats but that the temporal profile
      and the size of the responses are age- and sex-dependent. These findings are the
      first description of age- and sex-specific ET-1-induced nociception. PERSPECTIVE:
      Endothelin-1 is a vasoactive peptide released into the systemic circulation after
      stress and cold pain as well as locally in tissue after injury and disease. These
      findings suggest greater pain to stimuli that release endogenous endothelin in
      younger versus older organisms. This developmental approach to studying ET-1
      induced pain further illustrates the need for understanding pain mechanisms as a
      function of the development of the organism so as to better treat pain across the
      life span.

PMID- 17553750
TI  - Test-retest reliability of pressure pain threshold measurements of the upper limb
      and torso in young healthy women.
AB  - The goal of this study was to determine the intra- and interday reliability of
      pressure pain thresholds (PPT) in the upper extremity and torso of asymptomatic
      women. Nineteen healthy women (20-39 years) with no underlying musculoskeletal
      problems had 3 PPT trials performed on 8 different locations in the upper
      extremity and torso over 4 consecutive days. The test-retest reliability of PPT
      values was robust and highly consistent over the 4 days. The PPT intraclass
      correlations (ICC) were highly consistent and repeatable over the 4 days of
      testing (day 1: ICC = 0.94; day 2: ICC = 0.96; day 3: ICC = 0.97 and day 4: ICC =
      0.96). When compared with baseline measurements obtained on day 1, the PPT values
      were significantly lower (P < .05) on days 2, 3, and 4 at all 8 locations.
      Although the PPT test-retest reliability is robust and consistent throughout the
      4 days, there appears to be a similar overall decline in the magnitude of the
      absolute PPT response at each of the 8 locations. A specific explanation for this
      greater overall sensitivity in PPTs at all 8 locations is lacking; however, a
      centrally mediated alteration in pressure/pain sensation could contribute to the
      overall trend observed in this study. PERSPECTIVE: PPT measurements of the upper
      limb and torso will be significantly lower with repeated measures over a short
      period time. A standardized evaluation grid should be included in baseline so as
      to accurately evaluate the progression in shoulder rehabilitation in women with
      shoulder dysfunction.

PMID- 17553751
TI  - Hepatic nuclear receptor PPARalpha in the koala (Phascolarctos cinereus): cloning
      and molecular characterisation.
AB  - Peroxisome proliferator-activated receptor alpha (PPARalpha) is a member of the
      nuclear/steroid receptor gene superfamily that plays an essential role in fatty
      acid metabolism. PPARalpha modulates the expression of genes encoding peroxisomal
      fatty acid beta-oxidation enzymes and microsomal fatty acid hydroxylases CYP4As.
      We have previously reported that the obligate Eucalyptus feeder koala
      (Phascolarctos cinereus) exhibits a higher hepatic CYP4A activity and an absence
      of peroxisomal palmitoyl-CoA oxidation as compared to non-Eucalyptus feeders
      human, rat or wallaby. Here we describe the cloning, expression and molecular
      characterisation of koala hepatic PPARalpha. A full-length PPARalpha cDNA of size
      1515 bp was cloned by reverse transcription-polymerase chain reaction (RT-PCR)
      and rapid amplification of cDNA ends (RACE). The koala PPARalpha cDNA encodes a
      protein of 468 amino acids. Transfection of the koala PPARalpha cDNA into Cos-7
      cells resulted in the expression of a protein recognised by a rabbit anti-human
      PPARalpha polyclonal antibody. PPARalpha immunoreactive bands of the same
      molecular mass were detected in nuclear extracts of koala livers. The results of
      this study demonstrate the presence of koala hepatic PPARalpha which shares
      several common features with other published PPARalphas; however, it exhibits
      important differences in both the DNA and ligand binding domains.

PMID- 17553752
TI  - Polygonum cuspidatum, compared with baicalin and berberine, inhibits inducible
      nitric oxide synthase and cyclooxygenase-2 gene expressions in RAW 264.7
      macrophages.
AB  - Polygonum cuspidatum water extract (PCWE) was shown to be a potent inhibitor of
      lipopolysaccharide (LPS)-induced expression of inducible nitric oxide synthase
      (iNOS) and cyclooxygenase-2 (COX-2). PCWE was compared to baicalin isolated from
      Scutellaria baicalensis Georgi and berberine of Coptidis rhizoma and Phellodendri
      cortex, for their effects on LPS-induced nitric oxide (NO) production and iNOS
      and COX-2 gene expressions in RAW 264.7 macrophages. Both PCWE and the compounds
      inhibited LPS-induced NO production in a concentration-dependent manner without a
      cytotoxicity. The decrease in NO production was in parallel with the inhibition
      of LPS-induced iNOS gene expression by PCWE and the compounds. In contrast, iNOS
      enzyme activity was not inhibited by PCWE and two agents. In addition, only PCWE
      inhibited LPS-induced prostaglandin E2 (PGE2) production and COX-2 gene
      expression without affecting COX-2 enzyme activity, while baicalin or berberine
      did not. Furthermore, N-nitro-L-arginine (NLA) and N-nitro-L-arginine methyl
      ester (L-NAME) pretreatment enhanced LPS-induced iNOS protein expression, which
      was inhibited by these PCWE and two agents, although LPS-induced COX-2 protein
      expression was not affected by NLA and L-NAME. PCWE inhibited PGE2 production and
      COX-2 protein expression in NLA/LPS or L-NAME/LPS-co-treated RAW 264.7 cell,
      however, baicalin or berberine did not. From the results, it was concluded that
      co-treatment with NOS inhibitors and PCWE effectively blocks acute production of
      NO and inhibits expression of iNOS and COX-2 genes.

PMID- 17553753
TI  - Predictors of clinical response to gluten-free diet in patients diagnosed with
      diarrhea-predominant irritable bowel syndrome.
AB  - BACKGROUND & AIMS: Gluten sensitivity might cause abdominal symptoms in the
      absence of villous atrophy. We examined the prevalence of celiac disease
      associated serum antibodies in diarrhea-dominant irritable bowel syndrome (d-IBS)
      patients and their efficacy in combination with HLA-DQ2 expression to predict the
      response to gluten-free diet. METHODS: HLA-DQA1*0501/DQB1*0201 expression and
      celiac disease-associated IgA and IgG serum antibodies against gliadin and tissue
      transglutaminase were measured in 145 patients with d-IBS, 74 patients with
      untreated and treated celiac disease, and 57 patients with active IBD. Follow-up
      antibody levels, stool frequency, and gastrointestinal symptom scores were
      determined in 41 d-IBS patients (26 women, 15 men; median age, 46 years, range,
      30-67 years) who participated in a nonrandomized evaluation of 6 months of gluten
      free diet. RESULTS: Increased celiac disease-associated serum IgG, but not IgA,
      was found in the majority of patients with treated (55%) as in most patients with
      untreated celiac disease (97%). In d-IBS patients, celiac disease-associated
      serum IgG antibodies (37%) and HLA-DQ2 expression (39%) were more frequent than
      in IBD patients (18% and 23%, respectively). After 6 months of gluten-free diet,
      stool frequency and gastrointestinal symptom score returned to normal values in
      60% of d-IBS patients who were positive and in 12% who were negative for HLA-DQ2
      and celiac disease-associated serum IgG; both parameters combined yielded
      positive and negative predictive values of 56% (95% confidence interval, 30%-80%)
      and 88% (69%-97%), respectively. CONCLUSIONS: Celiac disease-associated serum IgG
      and HLA-DQ2 expression can identify likely responders to gluten-free diet in d
      IBS patients.

PMID- 17553755
TI  - Genetic clustering of Trypanosoma cruzi I lineage evidenced by intergenic
      miniexon gene sequencing.
AB  - American trypanosomiasis or Chagas disease is endemic in Latin America and caused
      by the flagellate Trypanosoma cruzi, which exhibits broad genetic variation. In
      various areas, the transmission of Chagas disease is ensured by sylvatic vectors,
      mainly carrying the evolutionary lineage I of T. cruzi. Despite its
      epidemiological importance, this lineage is poorly studied. Here, we investigated
      the genetic variability and the phylogenetic relationships within T. cruzi I
      using sequences of the non-transcribed spacer of miniexon genes. The variability
      was firstly analysed between 10 repeats of spacer-miniexon genes in two strains
      of T. cruzi I and in the CL Brener strain, showing lower intra-strain variability
      than inter-strain. Furthermore, the phylogenetic analysis of 19 T. cruzi I
      strains (49 copies in total) clusters the copies into at least three groups. Two
      evolutionary phenomena can be proposed to explain the partition of the strains:
      (i) an association between strains and Didelphis sp. hosts and (ii) geographical
      clustering between the North American and South American strains. Thereby, the
      miniexon gene is an attractive marker to establish the phylogeny of lineage I and
      explore relationships between T. cruzi and mammal hosts.

PMID- 17553754
TI  - Association between body size and colorectal adenoma recurrence.
AB  - BACKGROUND & AIMS: Obesity has been associated with increased risk for colorectal
      adenoma, although its role as a risk factor after polypectomy for recurrence is
      unclear. Therefore, we sought to evaluate the effect of anthropometric measures
      of obesity on adenoma after polypectomy. METHODS: Subjects with baseline adenomas
      (n = 2465) and follow-up colonoscopy data were drawn from 2 randomized trials
      designed to prevent adenoma recurrence. RESULTS: Over a mean follow-up period of
      3.1 years presence of a body mass index (BMI) > or = 30 kg/m2 was associated with
      a nonsignificant 17% increase in the odds for any adenoma recurrence among all
      subjects (odds ratio [OR], 1.17; 95% confidence interval [CI], 0.92-1.48). This
      result was confined to men (OR, 1.36; 95% CI, 1.01-1.83) and not observed for
      women (OR, 0.90; 95% CI, 0.60-1.33). Results for waist circumference did not
      reach statistical significance, although trends were similar to those for BMI.
      Analyses of the effects of obesity on more clinically significant lesions
      demonstrated that high BMI was a slightly stronger risk factor for advanced
      adenoma recurrences in men (OR, 1.62; 95% CI, 1.04-2.53) when compared with non
      advanced lesions (OR, 1.26; 95% CI, 0.91-1.75). In addition, we observed an
      association for obesity and odds of adenoma recurrence among participants
      reporting a family history of colorectal cancer (OR, 2.25; 95% CI, 1.32-3.84) but
      not for those without (OR, 1.00; 95% CI, 0.77 to 1.31; P(int) = P = .008).
      CONCLUSIONS: Our results support obesity as a risk factor for subsequent short
      interval (mean follow-up time 3.1 years) development of colorectal adenomas,
      particularly among men and persons with a family history of colorectal cancer.
      Furthermore, obesity in men appears to be strongly associated with the
      development of clinically advanced lesions.

PMID- 17553757
TI  - Characterisation of the sites of DNA damage-induced 53BP1 phosphorylation
      catalysed by ATM and ATR.
AB  - The 53BP1 tumour suppressor, an important regulator of genome stability, is
      phosphorylated in response to ionising radiation (IR) by the ATM protein kinase,
      itself an important regulator of cellular responses to DNA damage. The only known
      sites of phosphorylation in 53BP1 are Ser25 and/or Ser29 but 53BP1 lacking these
      residues is still phosphorylated after DNA damage. In this study, we use mass
      spectrometry-based together with bioinformatic analysis to identify novel DNA
      damage-regulated sites of 53BP1 phosphorylation. Several new sites were
      identified that conform to the consensus Ser/Thr-Gln motif phosphorylated by ATM
      and related kinases. Phospho-specific antibodies were raised, and were used to
      demonstrate ATM-dependent phosphorylation of these residues in 53BP1 after
      exposure of cells to IR. Surprisingly, 53BP1 was also phosphorylated on these
      residues after exposure of cells to UV light. In this case, 53BP1 phosphorylation
      did not require ATM but required ATR instead. These data reveal that 53BP1 is
      phosphorylated on multiple residues in response to different types of DNA damage,
      and that 53BP1 is regulated by ATR in response to UV-induced DNA damage.

PMID- 17553756
TI  - X-rays induce distinct patterns of somatic mutation in fetal versus adult
      hematopoietic cells.
AB  - There are a variety of mechanisms and pathways whereby cells safeguard their
      genomes in the face of environmental insults that damage DNA. Whether each of
      these pathways is equally robust at specific developmental stages in mammals and
      whether they are also modulated in a tissue-specific manner, however, are
      unclear. Here, we report that ionizing radiation (IR) produces different types of
      somatic mutations in fetal cells compared with adult cells of the same lineage.
      While 1 Gy of X-ray significantly induced intragenic point mutations in T cells
      of adult mice, no point mutational effect was observed when applied to fetuses.
      Fetal exposure to IR, on the other hand, led to a significant elevation of
      mitotic recombination in T cells, which was not observed in adults. Base excision
      repair (BER) activity was significantly lower in fetal hematopoietic cells than
      in adult cells, due to a low level of DNA polymerase beta, the rate-limiting
      enzyme in BER. In fetal hematopoietic cells, this low BER activity, together with
      a high rate of proliferation, causes X-ray-induced DNA lesions, such as base
      damage, single strand breaks and double strand breaks, to be repaired by
      homologous recombination, which we observe as mitotic recombination. Higher BER
      activity and a relatively lower rate of cell proliferation likely contribute to
      the significant induction of DNA point mutations in adults. Thus, the mutational
      response to IR is at least partly determined by the availability of specific
      repair pathways and other developmentally regulated phenotypes, such as mitotic
      index.

PMID- 17553758
TI  - Feasibility of nasal epithelial brushing for the study of airway epithelial
      functions in CF infants.
AB  - BACKGROUND: For a better understanding of the early stages of cystic fibrosis
      (CF), it is of major interest to study respiratory epithelial cells obtained as
      early as possible. Although bronchoalveolar lavage has been proposed for this
      purpose, nasal brushing, which is a much less invasive technique, has seldom been
      used in CF infants. The aim of the present study was to examine in a few infants
      the feasibility of a nasal brushing technique for studies of airway epithelial
      functions in very young CF infants. METHODS: In 5 CF (median age 12, range 1-18
      months) and 10 control infants (median age 5, range 1-17 months), a nasal
      brushing was performed by means of a soft sterile cytology brush, after
      premedication with oral paracetamol (15 mg/kg body weight) and rectal midazolam
      (0.2 mg/kg body weight). Samples were used for microbiological, cytological and
      functional studies. RESULTS: The procedure was well tolerated. Number of cells
      collected was similar in CF and non-CF patients (CF: median 230x10(3), range
      42x10(3)-900x10(3); non-CF: median 340x10(3), range 140x10(3)-900x10(3)). Median
      number of viable cells was 67% (range 31-84%). Freshly obtained samples were
      successfully used for studies of ciliary beating frequency and cAMP-dependent
      chloride efflux. In 7 out of 17 cell cultures, confluence was obtained (CF: 2 out
      of 7; non-CF: 5 out of 10). The feasibility of studying protein release and mRNA
      expression of IL-8, IL-6 and TNF-alpha, under basal conditions and after
      stimulation by Pseudomonas aeruginosa, was demonstrated. CONCLUSIONS: By means of
      a simple nasal brushing technique easily performed and well tolerated, it is
      feasible, in infants, to harvest respiratory cells in sufficient amounts to study
      the airway epithelium using a broad range of techniques including cell culture.

PMID- 17553760
TI  - Biochemical and functional characterization of UDP-galactose 4-epimerase from
      Aeromonas hydrophila.
AB  - Bacteria of genus Aeromonas, responsible for a variety of pathological conditions
      in humans and fish, are ubiquitous waterborne bacteria. Aeromonas produces
      several virulent factors including a complex of lipopolysaccharide and surface
      array protein, involved in colonization. UDP-galactose 4-epimerase (GalE)
      catalyzes the production of UDP-galactose, a precursor for lipopolysaccharide
      biosynthesis, and thus is an important drug target. GalE exhibits interspecies
      variation and heterogeneity at its structural and functional level and therefore,
      the differences between the GalE of the host and the pathogen can be exploited
      for drug designing. In the present study, we report biochemical and functional
      characterization of the recombinant GalE of Aeromonas hydrophila. Unlike GalE
      reported from all other species, the purified recombinant GalE of A. hydrophila
      was found to exist as a monomer. This is the first report of UDP-galactose 4
      epimerase from any species being a monomer. The molecular mass of the 6xHis-rGalE
      was determined to be 38271.477 (m/z). The 6xHis-rGalE with a K(m) of 0.5 mM for
      UDP-galactose exhibited optimum activity at 37 degrees C and pH 8-9.
      Spectrofluorimetric and CD analysis confirmed that the thermal inactivation was
      due to structural changes and not due to the NAD-dissociation. A relatively more
      ordered structure of the enzyme at pH 8 and 9 as compared to that at pH 6 or 7
      suggests a key role of the electrostatic interactions in maintaining its native
      tertiary structure.

PMID- 17553761
TI  - Diffuse-interface theory for structure formation and release behavior in
      controlled drug release systems.
AB  - A common method of controlling drug release has been to incorporate the drug into
      a polymer matrix, thereby creating a diffusion barrier that slows the rate of
      drug release. It has been demonstrated that the internal microstructure of these
      drug-polymer composites can significantly impact the drug release rate. However,
      the effect of processing conditions during manufacture on the composite structure
      and the subsequent effects on release behavior are not well understood. We have
      developed a diffuse-interface theory for microstructure evolution that is based
      on interactions between drug, polymer and solvent species, all of which may be
      present in either crystalline or amorphous states. Because the theory can be
      applied to almost any specific combination of material species and over a wide
      range of environmental conditions, it can be used to elucidate and quantify the
      relationships between processing, microstructure and release response in
      controlled drug release systems. Calculations based on the theory have now
      demonstrated that, for a characteristic delivery system, variations in
      microstructure arising due to changes in either drug loading or processing time,
      i.e. evaporation rate, could have a significant impact on both the bulk release
      kinetics and the uniformity of release across the system. In fact, we observed
      that changes in process time alone can induce differences in bulk release of
      almost a factor of two and typical non-uniformities of +/-30% during the initial
      periods of release. Because these substantial variations may have deleterious
      clinical ramifications, it is critical that both the system microstructure and
      the control of that microstructure are considered to ensure the device will be
      both safe and effective in clinical use.

PMID- 17553762
TI  - Stem cell therapies for perinatal brain injuries.
AB  - This chapter reviews four groups of paediatric brain injury. The pathophysiology
      of these injuries is discussed to establish which cells are damaged and therefore
      which cells represent targets for cell replacement. Next, we review potential
      sources of cellular replacements, including embryonic stem cells, fetal and
      neonatal neural stem cells and a variety of mesenchymal stem cells. The
      advantages and disadvantages of each source are discussed. We review published
      studies to illustrate where stem cell therapies have been evaluated for
      therapeutic gain and discuss the hurdles that will need to be overcome to achieve
      therapeutic benefit. Overall, we conclude that children with paediatric brain
      injuries or inherited genetic disorders that affect the brain are worthy
      candidates for stem cell therapeutics.

PMID- 17553763
TI  - BMP-silk composite matrices heal critically sized femoral defects.
AB  - Clinical drawbacks of bone grafting prompt the search for alternative bone
      augmentation technologies such as use of growth and differentiation factors, gene
      therapy, and cell therapy. Osteopromotive matrices are frequently employed for
      the local delivery and controlled release of these augmentation agents. Some
      matrices also provide an osteoconductive scaffold to support new bone growth. In
      this study, silkworm-derived silk fibroin was evaluated as an osteoconductive
      matrix for healing critical sized mid-femoral segmental defects in nude rats.
      Four treatment groups were assessed over eight weeks: silk scaffolds (SS) with
      recombinant human BMP-2 (rhBMP-2) and human mesenchymal stem cells (HMSC) that
      had been pre-differentiated along an osteoblastic lineage ex vivo (Group I;
      pdHMSC/rhBMP-2/SS); SS with rhBMP-2 and undifferentiated HMSCs (Group II;
      udHMSC/rhBMP-2/SS); SS and rhBMP-2 alone (Group III; rhBMP-2/SS); and empty
      defects (Group IV). Bi-weekly radiographs revealed a progressive and similar
      increase in Group I-III mean defect mineralization through post-operative week
      (POW) 8. Radiographs, dual energy x-ray absorptiometry, and micro-computed
      tomography confirmed that Groups I-III exhibited similar substantial and
      significantly (p<0.05) greater defect mineralization at POW 8 than the unfilled
      Group IV defects which remained void of bone. No significant differences in
      Groups I-III defect healing at POW 8 were apparent using these same assays or
      mechanical testing. Histology at POW 8 revealed moderately good bridging of the
      parent diaphyseal cortices with woven and lamellar bone bridging islands of silk
      matrix in Groups I and III. Group II defects possessed comparatively less new
      bone which was most abundant adjacent to the parent bone margins. Elsewhere the
      silk matrix was more often enveloped by poorly differentiated loose fibrous
      connective tissue. Group IV defects showed minimal new bone formation. None of
      the treatment groups attained the mean mineralization or the mean biomechanical
      strength of identical defects implanted with SS and pdHMSCs alone in a previous
      study. However, addition of rhBMP-2 to SS prompted more bone than was previously
      generated using udHMSC/SS or SS alone. These data imply the clinical potential of
      silk scaffolds and rhBMP-2 as composite osteopromotive implants when used alone
      or with select stem cell populations. Additional studies in larger species are
      now warranted.

PMID- 17553767
TI  - Fisheries in the Southern Ocean: an ecosystem approach.
AB  - The Commission for the Conservation of Antarctic Marine Living Resources (CCAMLR)
      is bound by its Article II, 3 to follow an ecosystem approach to management. This
      approach has been extended to the application of a precautionary approach in the
      late 1980s. In our review, we deal primarily with the science-related aspects of
      CCAMLR and its development towards an ecosystem approach to the management of the
      living resources of the Southern Ocean. To assist the Commission in meeting its
      objectives, as set out in Article II, 3, the Scientific Committee established the
      CCAMLR Ecosystem Monitoring Programme to detect possible effects of krill fishing
      on the performance of top-level predators, such as albatrosses, penguins, petrels
      and fur seals. Fisheries in the Southern Ocean followed the fate of other
      fisheries worldwide in which target species were depleted to low level one after
      the other. Currently, two types of fisheries are open: the longline fisheries on
      Patagonian toothfish (Dissostichus eleginoides) and Antarctic toothfish
      (Dissostichus mawsoni) and the trawl fisheries on mackerel icefish
      (Champsocephalus gunnari). Both fisheries are managed in a single-species
      context, however, with conservation measures in place to protect by-catch
      species, such as rattails (Macrouridae) and skates and rays (Rajidae). Two major
      problems still exist in fisheries in the Southern Ocean: the by-catch of birds in
      longline fisheries primarily in the Indian Ocean and the high level of IUU
      fishing again in the Indian Ocean. Both, the by-catch of birds and high IUU
      catches undermine the credibility of CCAMLR to safeguard the marine living
      resources in the Southern Ocean.

PMID- 17553768
TI  - Spatial and temporal variability across life's hierarchies in the terrestrial
      Antarctic.
AB  - Antarctica and its surrounding islands lie at one extreme of global variation in
      diversity. Typically, these regions are characterized as being species poor and
      having simple food webs. Here, we show that terrestrial systems in the region are
      nonetheless characterized by substantial spatial and temporal variations at
      virtually all of the levels of the genealogical and ecological hierarchies which
      have been thoroughly investigated. Spatial variation at the individual and
      population levels has been documented in a variety of genetic studies, and in
      mosses it appears that UV-B radiation might be responsible for within-clump
      mutagenesis. At the species level, modern molecular methods have revealed
      considerable endemism of the Antarctic biota, questioning ideas that small
      organisms are likely to be ubiquitous and the taxa to which they belong species
      poor. At the biogeographic level, much of the relatively small ice-free area of
      Antarctica remains unsurveyed making analyses difficult. Nonetheless, it is clear
      that a major biogeographic discontinuity separates the Antarctic Peninsula and
      continental Antarctica, here named the 'Gressitt Line'. Across the Southern Ocean
      islands, patterns are clearer, and energy availability is an important correlate
      of indigenous and exotic species richness, while human visitor numbers explain
      much of the variation in the latter too. Temporal variation at the individual
      level has much to do with phenotypic plasticity, and considerable life-history
      and physiological plasticity seems to be a characteristic of Antarctic
      terrestrial species. Environmental unpredictability is an important driver of
      this trait and has significantly influenced life histories across the region and
      probably throughout much of the temperate Southern Hemisphere. Rapid climate
      change-related alterations in the range and abundance of several Antarctic and
      sub-Antarctic populations have taken place over the past several decades. In many
      sub-Antarctic locations, these have been exacerbated by direct and indirect
      effects of invasive alien species. Interactions between climate change and
      invasion seem set to become one of the most significant conservation problems in
      the Antarctic. We conclude that despite the substantial body of work on the
      terrestrial biodiversity of the Antarctic, investigations of interactions between
      hierarchical levels remain scarce. Moreover, little of the available information
      is being integrated into terrestrial conservation planning, which lags far behind
      in this region by comparison with most others.

PMID- 17553769
TI  - Global change tipping points: above- and below-ground biotic interactions in a
      low diversity ecosystem.
AB  - Low diversity ecosystems are expected to be more vulnerable to global changes
      although they have received less attention than high diversity ecosystems.
      Addressing the present state of the Antarctic Dry Valley region by focusing on
      the potential global changes that may alter the coupling of above- and below
      ground species and ecosystem processes is a realistic and critical need that has
      value beyond the Antarctic community. Presented here are suggested implications
      of global change on the Dry Valley terrestrial systems and how these effects
      might be manifested in the future.

PMID- 17553770
TI  - Environmental forcing and Southern Ocean marine predator populations: effects of
      climate change and variability.
AB  - The Southern Ocean is a major component within the global ocean and climate
      system and potentially the location where the most rapid climate change is most
      likely to happen, particularly in the high-latitude polar regions. In these
      regions, even small temperature changes can potentially lead to major
      environmental perturbations. Climate change is likely to be regional and may be
      expressed in various ways, including alterations to climate and weather patterns
      across a variety of time-scales that include changes to the long interdecadal
      background signals such as the development of the El Nino-Southern Oscillation
      (ENSO). Oscillating climate signals such as ENSO potentially provide a unique
      opportunity to explore how biological communities respond to change. This
      approach is based on the premise that biological responses to shorter-term sub
      decadal climate variability signals are potentially the best predictor of
      biological responses over longer time-scales. Around the Southern Ocean, marine
      predator populations show periodicity in breeding performance and productivity,
      with relationships with the environment driven by physical forcing from the ENSO
      region in the Pacific. Wherever examined, these relationships are congruent with
      mid-trophic-level processes that are also correlated with environmental
      variability. The short-term changes to ecosystem structure and function observed
      during ENSO events herald potential long-term changes that may ensue following
      regional climate change. For example, in the South Atlantic, failure of Antarctic
      krill recruitment will inevitably foreshadow recruitment failures in a range of
      higher trophic-level marine predators. Where predator species are not able to
      accommodate by switching to other prey species, population-level changes will
      follow. The Southern Ocean, though oceanographically interconnected, is not a
      single ecosystem and different areas are dominated by different food webs. Where
      species occupy different positions in different regional food webs, there is the
      potential to make predictions about future change scenarios.

PMID- 17553771
TI  - Evolutionary self-organization in complex fluids.
AB  - This paper explores the ability of molecular evolution to take control of
      collective physical phases, making the first decisive step from independent
      replicators towards cell-like collective structures. We develop a physical model
      of replicating combinatorial molecules in a ternary fluid of hydrocarbons,
      amphiphiles and water. Such systems are being studied experimentally in various
      laboratories to approach the synthesis of artificial cells, and are also relevant
      to the origin of cellular life. The model represents amphiphiles by spins on a
      lattice (with Ising coupling in the simplest case), coupled to replicating
      molecules that may diffuse on the lattice and react with each other. The presence
      of the replicating molecules locally modulates the phases of the complex fluid,
      and the physical replication process and/or mobility of the replicating molecules
      is influenced by the local amphiphilic configuration through an energetic
      coupling. Consequently, the replicators can potentially modify their environment
      to enhance their own replication. Through this coupling, the system can associate
      hereditary properties, and the potential for autonomous evolution, to self
      assembling mesoscale structures in the complex fluid. This opens a route to
      analyse the evolution of artificial cells. The models are studied using Monte
      Carlo simulation, and demonstrate the evolution of phase control. We achieve a
      unified combinatorial framework for the description of isotropic families of spin
      lattice models of complex phases, opening up the physical study of their
      evolution.

PMID- 17553772
TI  - Introduction. Antarctic ecology: from genes to ecosystems. Part 2. Evolution,
      diversity and functional ecology.
AB  - The Antarctic biota has evolved over the last 100 million years in increasingly
      isolated and cold conditions. As a result, Antarctic species, from micro
      organisms to vertebrates, have adapted to life at extremely low temperatures,
      including changes in the genome, physiology and ecological traits such as life
      history. Coupled with cycles of glaciation that have promoted speciation in the
      Antarctic, this has led to a unique biota in terms of biogeography, patterns of
      species distribution and endemism. Specialization in the Antarctic biota has led
      to trade-offs in many ecologically important functions and Antarctic species may
      have a limited capacity to adapt to present climate change. These include the
      direct effects of changes in environmental parameters and indirect effects of
      increased competition and predation resulting from altered life histories of
      Antarctic species and the impacts of invasive species. Ultimately, climate change
      may alter the responses of Antarctic ecosystems to harvesting from humans. The
      unique adaptations of Antarctic species mean that they provide unique models of
      molecular evolution in natural populations. The simplicity of Antarctic
      communities, especially from terrestrial systems, makes them ideal to investigate
      the ecological implications of climate change, which are difficult to identify in
      more complex systems.

PMID- 17553773
TI  - Cardiorespiratory performance during prolonged swimming tests with salmonids: a
      perspective on temperature effects and potential analytical pitfalls.
AB  - A prolonged swimming trial is the most common approach in studying steady-state
      changes in oxygen uptake, cardiac output and tissue oxygen extraction as a
      function of swimming speed in salmonids. The data generated by these sorts of
      studies are used here to support the idea that a maximum oxygen uptake is reached
      during a critical swimming speed test. Maximum oxygen uptake has a temperature
      optimum. Potential explanations are advanced to explain why maximum aerobic
      performance falls off at high temperature. The valuable information provided by
      critical swimming tests can be confounded by non-steady-state swimming
      behaviours, which typically occur with increasing frequency as salmonids approach
      fatigue. Two major concerns are noted. Foremost, measurements of oxygen uptake
      during swimming can considerably underestimate the true cost of transport near
      critical swimming speed, apparently in a temperature-dependent manner. Second,
      based on a comparison with voluntary swimming ascents in a raceway, forced
      swimming trials in a swim tunnel respirometer may underestimate critical swimming
      speed, possibly because fish in a swim tunnel respirometer are unable to sustain
      a ground speed.

PMID- 17553774
TI  - Evolution and biodiversity of Antarctic organisms: a molecular perspective.
AB  - The Antarctic biota is highly endemic, and the diversity and abundance of
      taxonomic groups differ from elsewhere in the world. Such characteristics have
      resulted from evolution in isolation in an increasingly extreme environment over
      the last 100 Myr. Studies on Antarctic species represent some of the best
      examples of natural selection at the molecular, structural and physiological
      levels. Analyses of molecular genetics data are consistent with the diversity and
      distribution of marine and terrestrial taxa having been strongly influenced by
      geological and climatic cooling events over the last 70 Myr. Such events have
      resulted in vicariance driven by continental drift and thermal isolation of the
      Antarctic, and in pulses of species range contraction into refugia and subsequent
      expansion and secondary contact of genetically distinct populations or sister
      species during cycles of glaciation. Limited habitat availability has played a
      major role in structuring populations of species both in the past and in the
      present day. For these reasons, despite the apparent simplicity or homogeneity of
      Antarctic terrestrial and marine environments, populations of species are often
      geographically structured into genetically distinct lineages. In some cases,
      genetic studies have revealed that species defined by morphological characters
      are complexes of cryptic or sibling species. Climate change will cause changes in
      the distribution of many Antarctic and sub-Antarctic species through affecting
      population-level processes such as life history and dispersal.

PMID- 17553775
TI  - The biodiversity and ecology of Antarctic lakes: models for evolution.
AB  - Antarctic lakes are characterised by simplified, truncated food webs. The lakes
      range from freshwater to hypersaline with a continuum of physical and chemical
      conditions that offer a natural laboratory in which to study evolution. Molecular
      studies on Antarctic lake communities are still in their infancy, but there is
      clear evidence from some taxonomic groups, for example the Cyanobacteria, that
      there is endemicity. Moreover, many of the bacteria have considerable potential
      as sources of novel biochemicals such as low temperature enzymes and anti-freeze
      proteins. Among the eukaryotic organisms survival strategies have evolved, among
      which dependence on mixotrophy in phytoflagellates and some ciliates is common.
      There is also some evidence of evolution of new species of flagellate in the
      marine derived saline lakes of the Vestfold Hills. Recent work on viruses in
      polar lakes demonstrates high abundance and high rates of infection, implying
      that they may play an important role in genetic exchange in these extreme
      environments.

PMID- 17553776
TI  - Thermal limits and adaptation in marine Antarctic ectotherms: an integrative
      view.
AB  - A cause and effect understanding of thermal limitation and adaptation at various
      levels of biological organization is crucial in the elaboration of how the
      Antarctic climate has shaped the functional properties of extant Antarctic fauna.
      At the same time, this understanding requires an integrative view of how the
      various levels of biological organization may be intertwined. At all levels
      analysed, the functional specialization to permanently low temperatures implies
      reduced tolerance of high temperatures, as a trade-off. Maintenance of membrane
      fluidity, enzyme kinetic properties (Km and k(cat)) and protein structural
      flexibility in the cold supports metabolic flux and regulation as well as
      cellular functioning overall. Gene expression patterns and, even more so, loss of
      genetic information, especially for myoglobin (Mb) and haemoglobin (Hb) in
      notothenioid fishes, reflect the specialization of Antarctic organisms to a
      narrow range of low temperatures. The loss of Mb and Hb in icefish, together with
      enhanced lipid membrane densities (e.g. higher concentrations of mitochondria),
      becomes explicable by the exploitation of high oxygen solubility at low metabolic
      rates in the cold, where an enhanced fraction of oxygen supply occurs through
      diffusive oxygen flux. Conversely, limited oxygen supply to tissues upon warming
      is an early cause of functional limitation. Low standard metabolic rates may be
      linked to extreme stenothermy. The evolutionary forces causing low metabolic
      rates as a uniform character of life in Antarctic ectothermal animals may be
      linked to the requirement for high energetic efficiency as required to support
      higher organismic functioning in the cold. This requirement may result from
      partial compensation for the thermal limitation of growth, while other functions
      like hatching, development, reproduction and ageing are largely delayed. As a
      perspective, the integrative approach suggests that the patterns of oxygen- and
      capacity-limited thermal tolerance are linked, on one hand, with the capacity and
      design of molecules and membranes, and, on the other hand, with life-history
      consequences and lifestyles typically seen in the permanent cold. Future research
      needs to address the detailed aspects of these interrelationships.

PMID- 17553777
TI  - Molecular ecophysiology of Antarctic notothenioid fishes.
AB  - The notothenioid fishes of the Southern Ocean surrounding Antarctica are
      remarkable examples of organismal adaptation to extreme cold. Their evolution
      since the mid-Miocene in geographical isolation and a chronically cold marine
      environment has resulted in extreme stenothermality of the extant species. Given
      the unique thermal history of the notothenioids, one may ask what traits have
      been gained, and conversely, what characters have been lost through change in the
      information content of their genomes. Two dramatic changes that epitomize such
      evolutionary transformations are the gain of novel antifreeze proteins, which are
      obligatory for survival in icy seawater, by most notothenioids and the
      paradoxical loss of respiratory haemoproteins and red blood cells, normally
      deemed indispensable for vertebrate life, by the species of a highly derived
      notothenioid family, the icefishes. Here, we review recent advances in our
      understanding of these traits and their evolution and suggest future avenues of
      investigation. The formerly coherent paradigm of notothenioid freeze avoidance,
      developed from three decades of study of antifreeze glycoprotein (AFGP) based
      cold adaptation, now faces challenges stemming from the recent discovery of
      antifreeze-deficient, yet freeze-resistant, early notothenioid life stages and
      from definitive evidence that the liver is not the physiological source of AFGPs
      in notothenioid blood. The resolution of these intriguing observations is likely
      to reveal new physiological traits that are unique to the notothenioids.
      Similarly, the model of AFGP gene evolution from a notothenioid pancreatic
      trypsinogen-like gene precursor is being expanded and refined based on genome
      level analyses of the linked AFGP loci and their ancestral precursors. Finally,
      the application of comparative genomics to study evolutionary change in the AFGP
      genotypes of cool-temperate notothenioids from sub-Antarctic habitats, where
      these genes are not necessary, will contribute to the mechanistic understanding
      of the dynamics of AFGP gene gain and loss. In humans and most vertebrates,
      mutations in the alpha- or beta-globin genes or defects in globin chain synthesis
      are causes of severe genetic disease. Thus, the 16 species of haemoglobinless,
      erythrocyte-null icefishes are surprising anomalies -- in fact, they could only
      have evolved and thrived due to relaxed selection pressure for oxygen-binding
      proteins in the cold, oxygen-rich waters of the Southern Ocean. Fifteen of the
      sixteen icefish species have lost most of the adult alphabeta-globin locus and
      retain only a small 3' fragment of the alpha-globin gene. The only exception to
      this pattern occurs in Neopagetopsis ionah, which possesses a disrupted alphabeta
      globin gene complex that probably represents a non-functional intermediate on the
      evolutionary pathway to near total globin gene extinction. By contrast, six of
      the icefish species fail to express myoglobin. The absence of myoglobin
      expression has occurred by several independent mutations and distinct mechanisms.
      Haemoprotein loss is correlated with dramatic increases in cellular mitochondrial
      density, heart size, blood volume and capillary bed volume. Evolution of these
      compensatory traits was probably facilitated by the homeostatic activity of
      nitric oxide, a key modulator of angiogenesis and mitochondrial biogenesis. These
      natural knockouts of the red blood cell lineage are an excellent genomic resource
      for erythroid gene discovery by comparative genomics, as illustrated for the
      newly described gene, bloodthirsty.

PMID- 17553778
TI  - Diversity and genomics of Antarctic marine micro-organisms.
AB  - Marine bacterioplanktons are thought to play a vital role in Southern Ocean
      ecology and ecosystem function, as they do in other ocean systems. However, our
      understanding of phylogenetic diversity, genome-enabled capabilities and specific
      adaptations to this persistently cold environment is limited. Bacterioplankton
      community composition shifts significantly over the annual cycle as sea ice melts
      and phytoplankton bloom. Microbial diversity in sea ice is better known than that
      of the plankton, where culture collections do not appear to represent organisms
      detected with molecular surveys. Broad phylogenetic groupings of Antarctic
      bacterioplankton such as the marine group I Crenarchaeota, alpha-Proteobacteria
      (Roseobacter-related and SAR-11 clusters), gamma-Proteobacteria (both cultivated
      and uncultivated groups) and Bacteriodetes-affiliated organisms in Southern Ocean
      waters are in common with other ocean systems. Antarctic SSU rRNA gene phylotypes
      are typically affiliated with other polar sequences. Some species such as
      Polaribacter irgensii and currently uncultivated gamma-Proteobacteria (Ant4D3 and
      Ant10A4) may flourish in Antarctic waters, though further studies are needed to
      address diversity on a larger scale. Insights from initial genomics studies on
      both cultivated organisms and genomes accessed through shotgun cloning of
      environmental samples suggest that there are many unique features of these
      organisms that facilitate survival in high-latitude, persistently cold
      environments.

PMID- 17553779
TI  - The effect of temperature and thermal acclimation on the sustainable performance
      of swimming scup.
AB  - There is a significant reduction in overall maximum power output of muscle at low
      temperatures due to reduced steady-state (i.e. maximum activation) power
      generating capabilities of muscle. However, during cyclical locomotion, a further
      reduction in power is due to the interplay between non-steady-state contractile
      properties of muscle (i.e. rates of activation and relaxation) and the
      stimulation and the length-change pattern muscle undergoes in vivo. In
      particular, even though the relaxation rate of scup red muscle is slowed greatly
      at cold temperatures (10 degrees C), warm-acclimated scup swim with the same
      stimulus duty cycles at cold as they do at warm temperature, not affording slow
      relaxing muscle any additional time to relax. Hence, at 10 degrees C, red muscle
      generates extremely low or negative work in most parts of the body, at all but
      the slowest swimming speeds. Do scup shorten their stimulation duration and
      increase muscle relaxation rate during cold acclimation? At 10 degrees C,
      electromyography (EMG) duty cycles were 18% shorter in cold-acclimated scup than
      in warm-acclimated scup. But contrary to the expectations, the red muscle did not
      have a faster relaxation rate, rather, cold-acclimated muscle had an
      approximately 50% faster activation rate. By driving cold- and warm-acclimated
      muscle through cold- and warm-acclimated conditions, we found a very large
      increase in red muscle power during swimming at 10 degrees C. As expected,
      reducing stimulation duration markedly increased power output. However, the
      increased rate of activation alone produced an even greater effect. Hence, to
      fully understand thermal acclimation, it is necessary to examine the whole system
      under realistic physiological conditions.

PMID- 17553780
TI  - The thalamus of the monotremes: cyto- and myeloarchitecture and chemical
      neuroanatomy.
AB  - Echidna and platypus brains were sectioned and stained by Nissl or myelin stains
      or immunocytochemically for calcium-binding proteins, gamma aminobutyric acid
      (GABA) or other antigens. Cyto- and myeloarchitecture revealed thalami that are
      fundamentally mammalian in organization, with the three principal divisions of
      the thalamus (epithalamus, dorsal thalamus and ventral thalamus) identifiable as
      in marsupials and eutherian mammals. The dorsal thalamus exhibits more nuclear
      parcellation than hitherto described, but lack of an internal medullary lamina,
      caused by splaying out of afferent fibre tracts that contribute to it in other
      mammals, makes identification of anterior, medial and intralaminar nuclear groups
      difficult. Differentiation of the ventral nuclei is evident with the ventral
      posterior nucleus of the platypus enormously expanded into the interior of the
      cerebral hemisphere, where it adopts a relationship to the striatum not seen in
      other mammals. Other nuclei such as the lateral dorsal become identifiable by
      expression of patterns of calcium-binding proteins identical to those found in
      other mammals. GABA cells are present in the ventral and dorsal thalamic nuclei,
      and in the ventral thalamus form a remarkable continuum with GABA cells of the
      two segments of the globus pallidus and pars reticulata of the substantia nigra.

PMID- 17553781
TI  - Identification of a vacuole-associated metalloreductase and its role in Ctr2
      mediated intracellular copper mobilization.
AB  - Copper is an essential trace metal whose biological utility is derived from its
      ability to cycle between oxidized Cu(II) and reduced Cu(I). Ctr1 is a high
      affinity plasma membrane copper permease, conserved from yeast to humans, that
      mediates the physiological uptake of Cu(I) from the extracellular environment. In
      the baker's yeast Saccharomyces cerevisiae, extracellular Cu(II) is reduced to
      Cu(I) via the action of the cell surface metalloreductase Fre1, similar to the
      human gp91(phox) subunit of the NADPH oxidase complex, which utilizes heme and
      flavins to catalyze electron transfer. The S. cerevisiae Ctr2 protein is
      structurally similar to Ctr1, localizes to the vacuole membrane, and mobilizes
      vacuolar copper stores to the cytosol via a mechanism that is not well
      understood. Here we show that Ctr2-1, a mutant form of Ctr2 that mislocalizes to
      the plasma membrane, requires the Fre1 plasma membrane metalloreductase for Cu(I)
      import. The conserved methionine residues that are essential for Ctr1 function at
      the plasma membrane are also essential for Ctr2-1-mediated Cu(I) uptake. We
      demonstrate that Fre6, a member of the yeast Fre1 metalloreductase protein
      family, resides on the vacuole membrane and functions in Ctr2-mediated vacuolar
      copper export, and cells lacking Fre6 phenocopy the Cu-deficient growth defect of
      ctr2Delta cells. Furthermore, both CTR2 and FRE6 mRNA levels are regulated by
      iron availability. Taken together these studies suggest that copper movement
      across intracellular membranes is mechanistically similar to that at the plasma
      membrane. This work provides a model for communication between the extracellular
      Cu(I) uptake and the intracellular Cu(I) mobilization machinery.

PMID- 17553782
TI  - Biogenesis of the essential Tim9-Tim10 chaperone complex of mitochondria: site
      specific recognition of cysteine residues by the intermembrane space receptor
      Mia40.
AB  - The mitochondrial intermembrane space (IMS) contains an essential machinery for
      protein import and assembly (MIA). Biogenesis of IMS proteins involves a
      disulfide relay between precursor proteins, the cysteine-rich IMS protein Mia40
      and the sulfhydryl oxidase Erv1. How precursor proteins are specifically directed
      to the IMS has remained unknown. Here we systematically analyzed the role of
      cysteine residues in the biogenesis of the essential IMS chaperone complex Tim9
      Tim10. Although each of the four cysteines of Tim9, as well as of Tim10, is
      required for assembly of the chaperone complex, only the most amino-terminal
      cysteine residue of each precursor is critical for translocation across the outer
      membrane and interaction with Mia40. Mia40 selectively recognizes cysteine
      containing IMS proteins in a site-specific manner in organello and in vitro. Our
      results indicate that Mia40 acts as a trans receptor in the biogenesis of
      mitochondrial IMS proteins.

PMID- 17553783
TI  - Constitutive phosphorylation mutation in Fas-associated death domain (FADD)
      results in early cell cycle defects.
AB  - Fas-associated death domain (FADD) is an adaptor molecule for the death receptor
      subfamily of the tumor necrosis factor receptor superfamily, but it is also
      required for cell proliferation. Cell cycle-specific regulation of FADD
      phosphorylation plays an important role in FADD proliferative function since mice
      with a mutant form of FADD mimicking constitutive phosphorylation at serine 191
      (FADD-D) exhibit defective T cell proliferation. Here we characterized these mice
      in detail and found that T cell development in 2-4-week-old mice is relatively
      normal, although mature FADD-D T cells manifest defective G(0) and G(1) to S
      transition with abnormalities in regulation of p130, p27 degradation,
      retinoblastoma protein phosphorylation, and CDK2 kinase activity. These
      downstream defects are further associated with the failure to up-regulate the
      forkhead box M1 cell cycle transcription factor, FoxM1. FADD-D protein is also
      mislocalized during cell cycle progression. Thus, regulation of FADD
      phosphorylation is crucial for proper cell cycle entry.

PMID- 17553784
TI  - Functional silencing of TATA-binding protein (TBP) by a covalent linkage of the N
      terminal domain of TBP-associated factor 1.
AB  - General transcription factor TFIID is comprised of TATA-binding protein (TBP) and
      TBP-associated factors (TAFs), together playing critical roles in regulation of
      transcription initiation. The TAF N-terminal domain (TAND) of yeast TAF1
      containing two subdomains, TAND1 (residues 10-37) and TAND2 (residues 46-71), is
      sufficient to interact with TBP and suppress the TATA binding activity of TBP.
      However, the detailed structural analysis of the complex between yeast TBP and
      TAND12 (residues 6-71) was hindered by its poor solubility and stability in
      solution. Here we report a molecular engineering approach where the N terminus of
      TBP is fused to the C terminus of TAND12 via linkers of various lengths
      containing (GGGS)(n) sequence, (n = 1, 2, 3). The length of the linker within the
      TAND12-TBP fusion has a significant effect on solubility and stability (SAS). The
      construct with (GGGS)(3) linker produces the best quality single-quantum
      coherence (HSQC) NMR spectrum with markedly improved SAS. In parallel to these
      observations, the TAND12-TBP fusion exhibits marked reduction of TBP function in
      binding to TAF1 as well as temperature sensitivity in in vivo yeast cell growth.
      Remarkably, the temperature sensitivity was proportional to the length of the
      linker in the fusions: the construct with (GGGS)(3) linker did not grow at 20
      degrees C, while those with (GGGS)(1) and (GGGS)(2) linkers did. These results
      together indicate that the native interaction between TBP and TAND12 is well
      maintained in the TAND12-(GGGS)(3)-TBP fusion and that this fusion approach
      provides an excellent model system to investigate the structural detail of the
      TBP-TAF1 interaction.

PMID- 17553785
TI  - Rapid P450 heme iron reduction by laser photoexcitation of Mycobacterium
      tuberculosis CYP121 and CYP51B1. Analysis of CO complexation reactions and
      reversibility of the P450/P420 equilibrium.
AB  - We demonstrate that photoexcitation of NAD(P)H reduces heme iron of Mycobacterium
      tuberculosis P450s CYP121 and CYP51B1 on the microsecond time scale. Rates of
      formation for the ferrous-carbonmonoxy (Fe(II)-CO) complex were determined across
      a range of coenzyme/CO concentrations. CYP121 reaction transients were biphasic.
      A hyperbolic dependence on CO concentration was observed, consistent with the
      presence of a CO binding site in ferric CYP121. CYP51B1 absorption transients for
      Fe(II)-CO complex formation were monophasic. The reaction rate was second order
      with respect to [CO], suggesting the absence of a CO-binding site in ferric
      CYP51B1. In the absence of CO, heme iron reduction by photoexcited NAD(P)H is
      fast ( approximately 10,000-11,000 s(-1)) with both P450s. For CYP121, transients
      revealed initial production of the thiolate-coordinated (P450) complex
      (absorbance maximum at 448 nm), followed by a slower phase reporting partial
      conversion to the thiol-coordinated P420 species (at 420 nm). The slow phase
      amplitude increased at lower pH values, consistent with heme cysteinate
      protonation underlying the transition. Thus, CO binding occurs to the thiolate
      coordinated ferrous form prior to cysteinate protonation. For CYP51B1, slow
      conversions of both the ferrous/Fe(II)-CO forms to species with spectral maxima
      at 423/421.5 nm occurred following photoexcitation in the absence/presence of CO.
      This reflected conversion from ferrous thiolate- to thiol-coordinated forms in
      both cases, indicating instability of the thiolate-coordinated ferrous CYP51B1.
      CYP121 Fe(II)-CO complex pH titrations revealed reversible spectral transitions
      between P450 and P420 forms. Our data provide strong evidence for P420 formation
      linked to reversible heme thiolate protonation, and demonstrate key differences
      in heme chemistry and CO binding for CYP121 and CYP51B1.

PMID- 17553786
TI  - Elevated zeaxanthin bound to oligomeric LHCII enhances the resistance of
      Arabidopsis to photooxidative stress by a lipid-protective, antioxidant
      mechanism.
AB  - The xanthophyll cycle has a major role in protecting plants from photooxidative
      stress, although the mechanism of its action is unclear. Here, we have
      investigated Arabidopsis plants overexpressing a gene encoding beta-carotene
      hydroxylase, containing nearly three times the amount of xanthophyll cycle
      carotenoids present in the wild-type. In high light at low temperature wild-type
      plants exhibited symptoms of severe oxidative stress: lipid peroxidation,
      chlorophyll bleaching, and photoinhibition. In transformed plants, which
      accumulate over twice as much zeaxanthin as the wild-type, these symptoms were
      significantly ameliorated. The capacity of non-photochemical quenching is not
      significantly different in transformed plants compared with wild-type and
      therefore an enhancement of this process cannot be the cause of the stress
      tolerant phenotype. Rather, it is concluded that it results from the antioxidant
      effect of zeaxanthin. 80-90% of violaxanthin and zeaxanthin in wild-type and
      transformed plants was localized to an oligomeric LHCII fraction prepared from
      thylakoid membranes. The binding of these pigments in intact membranes was
      confirmed by resonance Raman spectroscopy. Based on the structural model of
      LHCII, we suggest that the protein/lipid interface is the active site for the
      antioxidant activity of zeaxanthin, which mediates stress tolerance by the
      protection of bound lipids.

PMID- 17553787
TI  - The cyclin-dependent kinase inhibitors p15INK4B and p21CIP1 are critical
      regulators of fibrillar collagen-induced tumor cell cycle arrest.
AB  - The extracellular matrix is a crucial component in determining cell fate.
      Fibrillar collagen in its native form inhibits cell proliferation, whereas in its
      monomeric form it stimulates proliferation. The observation of elevated levels of
      p27(KIP1) in cells plated in the presence of fibrillar collagen has led to the
      assumption that this kinase inhibitor was responsible for cell cycle arrest on
      fibrillar collagen. Here we provide evidence that p15(INK4b), rather than
      p27(KIP1), is the cyclin-dependent kinase inhibitor responsible for G0/G1 arrest
      of human melanoma cells grown on fibrillar collagen. Additionally, we demonstrate
      that fibrillar collagen can also arrest cells at the G2 phase, which is mediated
      in part by p21(CIP1). Our data, in addition to identifying cyclin-dependent
      kinase inhibitors important in cell cycle arrest mediated by fibrillar collagen,
      demonstrate the complexity of cell cycle regulation and indicate that modulating
      a single cyclin-dependent kinase inhibitor does not disrupt cell proliferation in
      the presence of fibrillar collagen.

PMID- 17553788
TI  - Translational repression of MCL-1 couples stress-induced eIF2 alpha
      phosphorylation to mitochondrial apoptosis initiation.
AB  - The integrated stress response (ISR) integrates a broad range of environmental
      and endogenous stress signals to the phosphorylation of the alpha-subunit of
      eukaryotic translation initiation factor 2 (eIF2 alpha). Although intense or
      prolonged activation of this pathway is known to induce apoptosis, the molecular
      mechanisms coupling stress-induced eIF2 alpha phosphorylation to the cell death
      machinery have remained incompletely understood. In this study, we characterized
      apoptosis initiation in response to classical activators of the ISR (tunicamycin,
      UVC, elevated osmotic pressure, arsenite). We found that all applied stress
      stimuli activated a mitochondrial pathway of apoptosis initiation. Rapid and
      selective down-regulation of the anti-apoptotic BCL-2 family protein MCL-1
      preceded the activation of BAX, BAK, and caspases. Stabilization of MCL-1 blocked
      apoptosis initiation, while cells with reduced MCL-1 protein content were
      strongly sensitized to stress-induced apoptosis. Stress-induced elimination of
      MCL-1 occurred with unchanged protein turnover and independently of MCL-1 mRNA
      levels. In contrast, stress-induced phosphorylation of eIF2 alpha at Ser(51) was
      both essential and sufficient for the down-regulation of MCL-1 protein in
      stressed cells. These findings indicate that stress-induced phosphorylation of
      eIF2 alpha is directly coupled to mitochondrial apoptosis regulation via
      translational repression of MCL-1. Down-regulation of MCL-1 enables but not
      enforces apoptosis initiation in stressed cells.

PMID- 17553789
TI  - Importance of Leu99 in transmembrane segment M1 of the Na+, K+ -ATPase in the
      binding and occlusion of K+.
AB  - Twenty-six point mutations were introduced into the N-terminal and middle parts
      of transmembrane segment M1 of the Na+, K+ -ATPase and its cytosolic extension.
      None of the alterations to charged and polar residues in the N-terminal part of
      M1 and its cytosolic extension had any major effect on the cation binding
      properties, thus rejecting the hypothesis that these residues are involved in
      cation selectivity. By contrast, specific residues in the middle part of M1,
      particularly Leu(99), were found critical to K+ interaction of the enzyme. Hence,
      mutation L99A reduced the affinity for K+ activation of E2P dephosphorylation 17
      fold, and L99F reduced the equilibrium level of the K+-occluded intermediate
      [K2]E2 and increased the rate of K+ deocclusion 39-fold, i.e. more than seen for
      mutation E329Q of the cation-binding glutamate in M4. L99Q affected K+
      interaction in yet another way, the equilibrium level of [K2]E2 being slightly
      increased despite an increased rate of K+ deocclusion, suggesting that the K+
      ions leave and enter the occlusion pocket more frequently than in the wild type.
      L99Q furthermore affected the ability to discriminate between Na+ and K+ on the
      extracellular side. Our findings can be explained by a structural model in which
      Leu(99) and Glu(329) interact and cooperate in K+ binding and gating of the K+
      sites. The disturbance of K+ interaction in mutants with alteration to Leu(91),
      Phe(95), Ser(96), or Leu(98) could be a consequence of the roles of these
      residues in positioning the M1 helix optimally for the interaction between
      Leu(99) and Glu(329). Phe(95) may serve to stabilize the pivot for movement of M1
      through interaction with Ile(287) in M3.

PMID- 17553790
TI  - Interaction of integrin-linked kinase with the kidney chloride/bicarbonate
      exchanger, kAE1.
AB  - Kidney anion exchanger 1 (kAE1) mediates chloride/bicarbonate exchange at the
      basolateral membrane of kidney alpha-intercalated cells, thereby facilitating
      bicarbonate reabsorption into the blood. Human kAE1 lacks the N-terminal 65
      residues of the erythroid form (AE1, band 3), which are essential for binding of
      cytoskeletal and cytosolic proteins. Yeast two-hybrid screening identified
      integrin-linked kinase (ILK), a serine/threonine kinase, and an actin-binding
      protein as an interacting partner with the N-terminal domain of kAE1. Interaction
      between kAE1 and ILK was confirmed in co-expression experiments in HEK 293 cells
      and is mediated by a previously unidentified calponin homology domain in the kAE1
      N-terminal region. The calponin homology domain of kAE1 binds the C-terminal
      catalytic domain of ILK to enhance association of kAE1 with the actin
      cytoskeleton. Overexpression of ILK increased kAE1 levels at the cell surface as
      shown by flow cytometry, cell surface biotinylation, and anion transport activity
      assays. Pulse-chase experiments revealed that ILK associates with kAE1 early in
      biosynthesis, likely in the endoplasmic reticulum. ILK co-localized with kAE1 at
      the basolateral membrane of polarized Madin-Darby canine kidney cells and in
      alpha-intercalated cells of human kidneys. Taken together these results suggest
      that ILK and kAE1 traffic together from the endoplasmic reticulum to the
      basolateral membrane. ILK may provide a linkage between kAE1 and the underlying
      actin cytoskeleton to stabilize kAE1 at the basolateral membrane, resulting in
      higher levels of cell surface expression.

PMID- 17553791
TI  - Crystal structure of the VP4 protease from infectious pancreatic necrosis virus
      reveals the acyl-enzyme complex for an intermolecular self-cleavage reaction.
AB  - Infectious pancreatic necrosis virus (IPNV), an aquatic birnavirus that infects
      salmonid fish, encodes a large polyprotein (NH(2)-pVP2-VP4-VP3-COOH) that is
      processed through the proteolytic activity of its own protease, VP4, to release
      the proteins pVP2 and VP3. pVP2 is further processed to give rise to the capsid
      protein VP2 and three peptides that are incorporated into the virion. Reported
      here are two crystal structures of the IPNV VP4 protease solved from two
      different crystal symmetries. The electron density at the active site in the
      triclinic crystal form, refined to 2.2-A resolution, reveals the acyl-enzyme
      complex formed with an internal VP4 cleavage site. The complex was generated
      using a truncated enzyme in which the general base lysine was substituted. Inside
      the complex, the nucleophilic Ser(633)Ogamma forms an ester bond with the main
      chain carbonyl of the C-terminal residue, Ala(716), of a neighboring VP4. The
      structure of this substrate-VP4 complex allows us to identify the S1, S3, S5, and
      S6 substrate binding pockets as well as other substrate-VP4 interactions and
      therefore provides structural insights into the substrate specificity of this
      enzyme. The structure from the hexagonal crystal form, refined to 2.3-A
      resolution, reveals the free-binding site of the protease. Three-dimensional
      alignment with the VP4 of blotched snakehead virus, another birnavirus, shows
      that the overall structure of VP4 is conserved despite a low level of sequence
      identity ( approximately 19%). The structure determinations of IPNV VP4, the
      first of an acyl-enzyme complex for a Ser/Lys dyad protease, provide insights
      into the catalytic mechanism and substrate recognition of this type of protease.

PMID- 17553792
TI  - Disruption of the insulin-like growth factor type 1 receptor in osteoblasts
      enhances insulin signaling and action.
AB  - Defective bone formation is common in patients with diabetes, suggesting that
      insulin normally exerts anabolic actions in bone. However, because insulin can
      cross-activate the insulin-like growth factor type 1 receptor (IGF-1R), which
      also functions in bone, it has been difficult to establish the direct (IGF-1
      independent) actions of insulin in osteoblasts. To overcome this problem, we
      examined insulin signaling and action in primary osteoblasts engineered for
      conditional disruption of the IGF-1 receptor (DeltaIGF-1R). Calvarial osteoblasts
      from mice carrying floxed IGF-1R alleles were infected with adenoviral vectors
      expressing the Cre recombinase (Ad-Cre) or green fluorescent protein (Ad-GFP) as
      control. Disruption of IGF-1R mRNA (>90%) eliminated IGF-1R without affecting
      insulin receptor (IR) mRNA and protein expression and eliminated IGF-1R/IR
      hybrids. In DeltaIGF-1R osteoblasts, insulin signaling was markedly increased as
      evidenced by increased phosphorylation of insulin receptor substrate 1/2 and
      enhanced ERK/Akt activation. Microarray analysis of RNA samples from insulin
      treated, DeltaIGF-1R osteoblasts revealed striking changes in several genes known
      to be downstream of ERK including Glut-1 and c-fos. Treatment of osteoblasts with
      insulin induced Glut-1 mRNA, increased 2-[1,2-(3)H]-deoxy-d-glucose uptake, and
      enhanced proliferation. Moreover, insulin treatment rescued the defective
      differentiation and mineralization of DeltaIGF-1R osteoblasts, suggesting that IR
      signaling can compensate, at least in part, for loss of IGF-1R signaling. We
      conclude that insulin exerts direct anabolic actions in osteoblasts by activation
      of its cognate receptor and that the strength of insulin-generated signals is
      tempered through interactions with the IGF-1R.

PMID- 17553793
TI  - Inflammatory signaling pathways regulating ApoE gene expression in macrophages.
AB  - The atheroprotective role of apolipoprotein E (apoE) is well established. During
      inflammation, expression of apoE in macrophages is reduced leading to enhanced
      atheromatous plaque development. In the present study, we investigated the
      signaling pathways involved in the repression of apoE gene expression in response
      to lipopolysaccharide (LPS) treatment, a condition that mimics the inflammatory
      stress, in mouse macrophages RAW 264.7. We identified Tpl-2 and MEKK1 as the
      kinases that are primarily responsible for the down-regulation of apoE promoter
      activity by LPS. Using a dominant negative form of IkappaB, we established that
      Tpl-2 and MEKK1 signaling pathways converge to NF-kappaB acting on the apoE core
      promoter -55/+73. In addition to NF-kappaB activation, LPS also activated c-Jun
      via its phosphorylation by JNK. The activity of the apoE promoter was repressed
      by c-Jun, whereas small interference RNA-mediated inhibition of endogenous c-Jun
      expression reversed the inhibitory effect of Tpl-2 on the apoE promoter.
      Transfection experiments and DNA binding assays showed that the binding site for
      c-Jun is in the -55/+73 region of the apoE promoter. Finally, we showed that LPS
      inhibited apoE gene expression via activation of the Tpl-2/MEK/ERK pathway acting
      on a different apoE promoter region. In summary, LPS represses apoE gene
      expression in macrophages via signaling pathways that involve the upstream
      kinases Tpl-2 and MEKK1, the intermediate mitogen-activated protein kinases ERK
      and JNK, and the downstream transcription factors AP-1 and NF-kappaB that inhibit
      the apoE promoter activity via distinct regions.

PMID- 17553794
TI  - HCN2 and HCN4 isoforms self-assemble and co-assemble with equal preference to
      form functional pacemaker channels.
AB  - Hyperpolarization-activated cyclic nucleotide-modulated (HCN) "pacemaker" channel
      subunits are integral membrane proteins that assemble as tetramers to form
      channels in cardiac conduction tissue and nerve cells. Previous studies have
      suggested that the HCN2 and HCN4 channel isoforms physically interact when
      overexpressed in mammalian cells, but whether they are able to co-assemble and
      form functional channels remains unclear. The extent to which co-assembly occurs
      over self-assembly and whether HCN2-HCN4 heteromeric channels are formed in
      native tissue are not known. In this study, we show co-assembly of HCN2 and HCN4
      in live Chinese hamster ovary cells using bioluminescence resonance energy
      transfer (BRET(2)), a novel approach for studying tetramerization of ion channel
      subunits. Together with results from electrophysiological and imaging approaches,
      the BRET(2) data show that HCN2 and HCN4 subunits self-assemble and co-assemble
      with equal preference. We also demonstrate colocalization of HCN2 and HCN4 and a
      positive correlation of their intensities in the embryonic mouse heart using
      immunohistochemistry, as well as physical interactions between these isoforms in
      the rat thalamus by coimmunoprecipitation. Together, these data support the
      formation of HCN2-HCN4 heteromeric channels in native tissue.

PMID- 17553795
TI  - Glyceraldehyde-3-phosphate dehydrogenase enhances transcriptional activity of
      androgen receptor in prostate cancer cells.
AB  - Androgen receptor (AR) functions as a transcriptional factor for genes involved
      in proliferation and differentiation of normal and cancerous prostate cells.
      Coactivators that bind to AR are required for maximal androgen action. Here we
      report that increasing the expression of glyceraldehyde-3-phosphate dehydrogenase
      (GAPDH) in a prostate cancer cell line by as little as 1.8-fold enhances
      transcriptional activity of AR (but not the transcriptional activity of
      glucocorticoid receptor or estrogen receptor alpha) in a ligand-dependent manner
      and results in an increased expression of prostate-specific antigen. Small
      interference RNA-mediated knockdown of GAPDH significantly attenuated ligand
      activated AR transactivation. Immunoprecipitation analysis revealed the presence
      of an endogenous protein complex containing GAPDH and AR in both the cytoplasm
      and nucleus. Addition of a nuclear localization signal (NLS) to GAPDH (GAPDH-NLS)
      completely abolished the ability of GAPDH to transactivate AR. Neither wild-type
      GAPDH nor GAPDH-NLS enhanced transcriptional activity of mutant AR (AR Delta C
      Nuc) that is a constitutively active form of AR in the nucleus, even though GAPDH
      NLS formed a complex with wild-type AR or AR Delta C-Nuc. AR transactivation was
      enhanced by a mutant GAPDH lacking dehydrogenase activity. GAPDH enhanced the
      transcriptional activity of AR(T875A) activated by an antagonist such as
      hydroxyflutamide or cyproterone acetate. These results indicate that GAPDH
      functions as a coactivator with high selectivity for AR and enhances AR
      transactivation independent of its glycolytic activity. Further, these data
      suggest that formation of a GAPDH.AR complex in the cytoplasm rather than nucleus
      is essential for GAPDH to enhance AR transactivation.

PMID- 17553796
TI  - Miconazole induces changes in actin cytoskeleton prior to reactive oxygen species
      induction in yeast.
AB  - The antifungal compound miconazole inhibits ergosterol biosynthesis and induces
      reactive oxygen species (ROS) in susceptible yeast species. To further uncover
      the mechanism of miconazole antifungal action and tolerance mechanisms, we
      screened the complete set of haploid Saccharomyces cerevisiae gene deletion
      mutants for mutants with an altered miconazole sensitivity phenotype. We
      identified 29 S. cerevisiae genes, which when deleted conferred at least 4-fold
      hypersensitivity to miconazole. Major functional groups encode proteins involved
      in tryptophan biosynthesis, membrane trafficking including endocytosis,
      regulation of actin cytoskeleton, and gene expression. With respect to the
      antifungal activity of miconazole, we demonstrate an antagonism with tryptophan
      and a synergy with a yeast endocytosis inhibitor. Because actin dynamics and
      induction of ROS are linked in yeast, we further focused on miconazole-mediated
      changes in actin cytoskeleton organization. In this respect, we demonstrate that
      miconazole induces changes in the actin cytoskeleton, indicative of increased
      filament stability, prior to ROS induction. These data provide novel mechanistic
      insights in the mode of action of a ROS-inducing azole.

PMID- 17553797
TI  - Crystal structure of the N-terminal NC4 domain of collagen IX, a zinc binding
      member of the laminin-neurexin-sex hormone binding globulin (LNS) domain family.
AB  - Collagen IX, located on the surface of collagen fibrils, is crucial for cartilage
      integrity and stability. The N-terminal NC4 domain of the alpha1(IX) chain is
      probably important in this because it interacts with various macromolecules such
      as proteoglycans and cartilage oligomeric matrix protein. At least 17 distinct
      collagen polypeptides carry an NC4-like unit near their N terminus, but this
      report, describing the crystal structure of NC4 at 1.8-A resolution, represents
      the first atomic level structure for these domains. The structure is similar to
      previously characterized laminin-neurexin-sex hormone binding globulin (LNS)
      structures, dominated by an antiparallel beta-sheet sandwich. In addition, a zinc
      ion was found in a position similar to that of the metal binding site of other
      LNS domains. A partial backbone NMR assignment of NC4 was obtained and utilized
      in NMR titration studies to investigate the zinc binding in solution state and to
      quantitate the affinity of metal binding. The K(d) of 11.5 mM suggests a
      regulatory rather than a structural role for zinc in solution. NMR titration with
      a heparin tetrasaccharide revealed the presence of a secondary binding site for
      heparin on NC4, showing structural and functional conservation with
      thrombospondin-1, but a markedly reduced affinity for the ligand. Also the
      overall arrangement of the N and C termini of NC4 resembles most closely the N
      terminal domain of thrombospondin-1, distinguishing the two from the majority of
      the published LNS structures.

PMID- 17553798
TI  - Structural variation governs substrate specificity for organic anion transporter
      (OAT) homologs. Potential remote sensing by OAT family members.
AB  - Organic anion transporters (OATs, SLC22) interact with a remarkably diverse array
      of endogenous and exogenous organic anions. However, little is known about the
      structural features that determine their substrate selectivity. We examined the
      substrate binding preferences and transport function of olfactory organic anion
      transporter, Oat6, in comparison with the more broadly expressed transporter,
      Oat1 (first identified as NKT). In analyzing interactions of both transporters
      with over 40 structurally diverse organic anions, we find a correlation between
      organic anion potency (pKi) and hydrophobicity (logP) suggesting a hydrophobicity
      driven association with transporter-binding sites, which appears particularly
      prominent for Oat6. On the other hand, organic anion binding selectivity between
      Oat6 and Oat1 is influenced by the anion mass and net charge. Smaller mono-anions
      manifest greater potency for Oat6 and di-anions for Oat1. Comparative molecular
      field analysis confirms these mechanistic insights and provides a model for
      predicting new OAT substrates. By comparative molecular field analysis, both
      hydrophobic and charged interactions contribute to Oat1 binding, although it is
      predominantly the former that contributes to Oat6 binding. Together, the data
      suggest that, although the three-dimensional structures of these two transporters
      may be very similar, the binding pockets exhibit crucial differences.
      Furthermore, for six radiolabeled substrates, we assessed transport efficacy
      (Vmax) for Oat6 and Oat1. Binding potency and transport efficacy had little
      correlation, suggesting that different molecular interactions are involved in
      substrate binding to the transporter and translocation across the membrane.
      Substrate specificity for a particular transporter may enable design of drugs for
      targeting to specific tissues (e.g. olfactory mucosa). We also discuss how these
      data suggest a possible mechanism for remote sensing between OATs in different
      tissue compartments (e.g. kidney, olfactory mucosa) via organic anions.

PMID- 17553799
TI  - Conformational changes that effect oligomerization and initiate pore formation
      are triggered throughout perfringolysin O upon binding to cholesterol.
AB  - Pore formation by the cholesterol-dependent cytolysins (CDCs) requires the
      presence of cholesterol in the target membrane. Cholesterol was long thought to
      be the cellular receptor for these toxins, but not all CDCs require cholesterol
      for binding. Intermedilysin, secreted by Streptococcus intermedius, only binds to
      membranes containing the human protein CD59 but forms pores only if the membrane
      contains sufficient cholesterol. In contrast, perfringolysin O (PFO), secreted by
      Clostridium perfringens, only binds to membranes containing substantial amounts
      of cholesterol. Given that different steps in the assembly of various CDC pores
      require cholesterol, here we have analyzed to what extent cholesterol molecules,
      by themselves, can modulate the conformational changes associated with PFO
      oligomerization and pore formation. PFO binds to cholesterol when dispersed in
      aqueous solution, and this binding triggers the distant rearrangement of a beta
      strand that exposes an oligomerization interface. Moreover, upon binding to
      cholesterol, PFO forms a prepore complex, unfolds two amphipathic transmembrane
      beta-hairpins, and positions their nonpolar surfaces so they associate with the
      hydrophobic cholesterol surface. The interaction of PFO with cholesterol is
      therefore sufficient to initiate an irreversible sequence of coupled
      conformational changes that extend throughout the toxin molecule.

PMID- 17553800
TI  - Spatially segregated SNARE protein interactions in living fungal cells.
AB  - The machinery for trafficking proteins through the secretory pathway is well
      conserved in eukaryotes, from fungi to mammals. We describe the isolation of the
      snc1, sso1, and sso2 genes encoding exocytic SNARE proteins from the filamentous
      fungus Trichoderma reesei. The localization and interactions of the T. reesei
      SNARE proteins were studied with advanced fluorescence imaging methods. The SSOI
      and SNCI proteins co-localized in sterol-independent clusters on the plasma
      membrane in subapical but not apical hyphal regions. The vesicle SNARE SNCI also
      localized to the apical vesicle cluster within the Spitzenkorper of the growing
      hyphal tips. Using fluorescence lifetime imaging microscopy and Foerster
      resonance energy transfer analysis, we quantified the interactions between these
      proteins with high spatial resolution in living cells. Our data showed that the
      site of ternary SNARE complex formation between SNCI and SSOI or SSOII,
      respectively, is spatially segregated. SNARE complex formation could be detected
      between SNCI and SSOI in subapical hyphal compartments along the plasma membrane,
      but surprisingly, not in growing hyphal tips, previously thought to be the main
      site of exocytosis. In contrast, SNCI.SSOII complexes were found exclusively in
      growing apical hyphal compartments. These findings demonstrate spatially distinct
      sites of plasma membrane SNARE complex formation in fungi and the existence of
      multiple exocytic SNAREs, which are functionally and spatially segregated. This
      is the first demonstration of spatially regulated SNARE interactions within the
      same membrane.

PMID- 17553801
TI  - An integrin-tetraspanin interaction required for cellular innate immune responses
      of an insect, Manduca sexta.
AB  - In their encounters with foreign intruders, the cells of the insect innate immune
      system, like those of the mammalian immune system, exhibit both humoral and cell
      mediated responses. Some intruders can be dispatched by the humoral immune system
      alone, but many must be phagocytosed by individual hemocytes or encapsulated by
      interacting hemocytes. Surface proteins of hemocytes control the abrupt
      transition of hemocytes from resting, nonadherent cells to activated, adherent
      cells during these cell-mediated responses. Two of these surface proteins, an
      integrin and a tetraspanin, interact during this adhesive transition. As
      demonstrated with a hemocyte adhesion assay and a surface plasmon resonance
      assay, the large extracellular loop of tetraspanin D76 binds to a hemocyte
      specific integrin of Manduca sexta. The interaction between the large
      extracellular loop domain and hemocyte-specific integrin is interrupted not only
      by a monoclonal antibody (MS13) that binds to a domain of beta-integrin known to
      be a ligand-binding site for cell adhesion but also by double-stranded beta
      integrin RNA. Transfected S2 cells expressing tetraspanin mediate adhesion of
      hemocytes. A monoclonal antibody to tetraspanin D76 perturbs the cell-mediated
      immune response of encapsulation. These studies involving antibody blocking, RNA
      interference, and binding assays imply a trans interaction of integrin and
      tetraspanin on hemocyte surfaces.

PMID- 17553802
TI  - Differential regulation of ATP binding cassette protein A1 expression and ApoA-I
      lipidation by Niemann-Pick type C1 in murine hepatocytes and macrophages.
AB  - Niemann-Pick type C1 (Npc1) protein inactivation results in lipid accumulation in
      late endosomes and lysosomes, leading to a defect of ATP binding cassette protein
      A1 (Abca1)-mediated lipid efflux to apolipoprotein A-I (apoA-I) in macrophages
      and fibroblasts. However, the role of Npc1 in Abca1-mediated lipid efflux to apoA
      I in hepatocytes, the major cells contributing to HDL formation, is still
      unknown. Here we show that, whereas lipid efflux to apoA-I in Npc1-null
      macrophages is impaired, the lipidation of endogenously synthesized apoA-I by low
      density lipoprotein-derived cholesterol or de novo synthesized cholesterol or
      phospholipids in Npc1-null hepatocytes is significantly increased by about 1-, 3
      , and 8-fold, respectively. The increased cholesterol efflux reflects a major
      increase of Abca1 protein in Npc1-null hepatocytes, which contrasts with the
      decrease observed in Npc1-null macrophages. The increased Abca1 expression is
      largely post-transcriptional, because Abca1 mRNA is only slightly increased and
      Lxr alpha mRNA is not changed, and Lxr alpha target genes are reduced. This
      differs from the regulation of Abcg1 expression, which is up-regulated at both
      mRNA and protein levels in Npc1-null cells. Abca1 protein translation rate is
      higher in Npc1-null hepatocytes, compared with wild type hepatocytes as measured
      by [(35)S]methionine incorporation, whereas there is no difference for the
      degradation of newly synthesized Abca1 in these two types of hepatocytes.
      Cathepsin D, which we recently identified as a positive modulator of Abca1, is
      markedly increased at both mRNA and protein levels by Npc1 inactivation in
      hepatocytes but not in macrophages. Consistent with this, inhibition of cathepsin
      D with pepstatin A reduced the Abca1 protein level in both Npc1-inactivated and
      WT hepatocytes. Therefore, Abca1 expression is specifically regulated in
      hepatocytes, where Npc1 activity modulates cathepsin D expression and Abca1
      protein translation rate.

PMID- 17553803
TI  - ATP-induced structural transitions in PAN, the proteasome-regulatory ATPase
      complex in Archaea.
AB  - ATP binding to the PAN-ATPase complex in Archaea or the homologous 19 S protease
      regulatory complex in eukaryotes induces association with the 20 S proteasome and
      opening of its substrate entry channel, whereas ATP hydrolysis allows unfolding
      of globular substrates. To clarify the conformational changes associated with ATP
      binding and hydrolysis, we used protease sensitivity to monitor the conformations
      of the PAN ATPase from Methanococcus jannischii. Exhaustive trypsin treatment of
      PAN generated five distinct fragments, two of which differed when a nucleotide
      (either ATP, ATP gamma S, or ADP) was bound. Surprisingly, the nucleotide
      concentrations altering protease sensitivity were much lower (K(a) 20-40 microm)
      than are required for ATP-dependent protein breakdown by the PAN-20S proteasome
      complex (K(m) approximately 300-500 microm). Unlike trypsin, proteinase K yielded
      several fragments that differed in the ATP gamma S and ADP-bound forms, and thus
      revealed conformational transitions associated with ATP hydrolysis. Mapping the
      fragments generated by each revealed that nucleotide binding and hydrolysis
      induce local conformational changes, affecting the Walker A and B nucleotide
      binding motif, as well as global changes extending to its carboxyl terminus. The
      location and overlap of the fragments also suggest that the conformation of the
      six subunits is not identical, probably because they do not all bind ATP
      simultaneously. Partial nucleotide occupancy was supported by direct assays,
      which demonstrated that, at saturating conditions, only four nucleotides are
      bound to hexameric PAN. Using the protease protection maps, we modeled the
      conformational changes associated with ATP binding and hydrolysis in PAN based on
      the x-ray structures of the homologous AAA ATPase, HslU.

PMID- 17553804
TI  - Characterization of a factor Xa binding site on factor Va near the Arg-506
      activated protein C cleavage site.
AB  - Prothrombin is proteolytically activated by the prothrombinase complex comprising
      the serine protease Factor (F) Xa complexed with its cofactor, FVa. Based on
      inhibition of the prothrombinase complex by synthetic peptides, FVa residues 493
      506 were proposed as a FXa binding site. FVa is homologous to FVIIIa, the
      cofactor for the FIXa protease, in the FX-activating complex, and FVIIIa residues
      555-561 (homologous to FVa residues 499-506) are recognized as a FIXa binding
      sequence. To test the hypothesis that FVa residues 499-505 contribute to FXa
      binding, we created the FVa loop swap mutant (designated 499-505(VIII) FV) with
      residues 499-505 replaced by residues 555-561 of FVIIIa, which differ at five of
      seven positions. Based on kinetic measurements and spectroscopic titrations, this
      FVa loop swap mutant had significantly reduced affinity for FXa. The fully formed
      prothrombinase complex containing this FVa mutant had fairly normal kinetic
      parameters (k(cat) and K(m)) for cleavage of prothrombin at Arg-320. However,
      small changes in both Arg-320 and Arg-271 cleavage rates result together in a
      moderate change in the pathway of prothrombin activation. Although residues 499
      505 directly precede the Arg-506 cleavage site for activated protein C (APC), the
      499-505(VIII) FVa mutant was inactivated entirely normally by APC. These results
      suggest that this A2 domain sequence of the FVa and FVIIIa cofactors evolved to
      have different specificity for binding FXa and FIXa while retaining compatibility
      as substrate for APC. In an updated three-dimensional model for the FVa
      structure, residues 499-505, along with Arg-506, Arg-306, and other previously
      suggested FXa binding sequences, delineate a continuous surface on the A2 domain
      that is strongly implicated as an extended FXa binding surface in the
      prothrombinase complex.

PMID- 17553805
TI  - The human mucin MUC4 is transcriptionally regulated by caudal-related homeobox,
      hepatocyte nuclear factors, forkhead box A, and GATA endodermal transcription
      factors in epithelial cancer cells.
AB  - The human gene MUC4 encodes a large transmembrane mucin that is developmentally
      regulated and expressed along the undifferentiated pseudostratified epithelium,
      as early as 6.5 weeks during fetal development. Immunohistochemical analysis of
      Muc4 expression in developing mouse lung and gastrointestinal tract showed a
      different spatio-temporal pattern of expression before and after
      cytodifferentiation. The molecular mechanisms governing MUC4 expression during
      development are, however, unknown. Hepatocyte nuclear factors (HNF), forkhead box
      A (FOXA), GATA, and caudal-related homeobox transcription factors (TFs) are known
      to control cell differentiation of gut endoderm derived-tissues during embryonic
      development. They also control the expression of cell- and tissue-specific genes
      and may thus control MUC4 expression. To test this hypothesis, we studied and
      deciphered the molecular mechanisms responsible for MUC4 transcriptional
      regulation by these TFs. Experiments using small interfering RNA, cell co
      transfection, and site-directed mutagenesis indicated that MUC4 is regulated at
      the transcriptional level by CDX-1 and -2, HNF-1 alpha and -1 beta, FOXA1/A2, HNF
      4 alpha and -4 gamma, and GATA-4, -5, and -6 factors in a cell-specific manner.
      Binding of TFs was assessed by chromatin immunoprecipitation, and gel-shift
      assays. Altogether, these results demonstrate that MUC4 is a target gene of
      endodermal TFs and thus point out an important role for these TFs in regulating
      MUC4 expression during epithelial differentiation during development, cancer, and
      repair.

PMID- 17553806
TI  - The effects of mTOR-Akt interactions on anti-apoptotic signaling in vascular
      endothelial cells.
AB  - Recent studies have determined that mTOR mediates the activation of the protein
      kinase Akt in several cell types, but little is known about the association
      between mTOR and Akt in vascular endothelial cells. Furthermore, the functional
      significance of mTOR/Akt signaling has not been characterized in the endothelium.
      In these studies we treated endothelial cells with the mTOR inhibitor rapamycin,
      and we found that it decreases Akt phosphorylation and activity, as determined by
      phosphorylation of its substrate glycogen synthase kinase-3. This effect of
      rapamycin on Akt phosphorylation could not be demonstrated in endothelial cells
      transfected with a rapamycin-resistant mTOR construct. Also, in the presence of
      rapamycin, vascular endothelial growth factor, tumor necrosis factor, and insulin
      failed to phosphorylate Akt, further indicating that mTOR regulates Akt
      activation in endothelial cells. The activation of Akt is well established to
      mediate pro-survival signals. In part this is mediated via the phosphorylation
      and inactivation of the pro-apoptotic Akt substrates Foxo1 and Foxo3a. We find
      that rapamycin totally blocks vascular endothelial growth factor and Akt
      inducible phosophorylation of these transcription factors in endothelial cells.
      Furthermore, inhibition of Akt activity by rapamycin increased the number of
      endothelial cells undergoing apoptosis after serum withdrawal as well as after
      stimulation by vascular endothelial growth factor or tumor necrosis factor. Taken
      together these observations demonstrate first, that mTOR regulates the
      phosphorylation and activation of Akt in endothelial cells and, second, that a
      major effect of mTOR inhibition in endothelial cells is to suppress Akt-inducible
      pro-survival signals.

PMID- 17553807
TI  - Thrombin-activatable fibrinolysis inhibitor binds to Streptococcus pyogenes by
      interacting with collagen-like proteins A and B.
AB  - Regulation of proteolysis is a critical element of the host immune system and
      plays an important role in the induction of pro- and anti-inflammatory reactions
      in response to infection. Some bacterial species take advantage of these
      processes and recruit host proteinases to their surface in order to counteract
      the host attack. Here we show that Thrombin-activatable Fibrinolysis Inhibitor
      (TAFI), a zinc-dependent procarboxypeptidase, binds to the surface of group A
      streptococci of an M41 serotype. The interaction is mediated by the streptococcal
      collagen-like surface proteins A and B (SclA and SclB), and the streptococcal
      associated TAFI is then processed at the bacterial surface via plasmin and
      thrombin-thrombomodulin. These findings suggest an important role for TAFI in the
      modulation of host responses by streptococci.

PMID- 17553808
TI  - Cyclic AMP-dependent protein kinase phosphorylation of Drp1 regulates its GTPase
      activity and mitochondrial morphology.
AB  - Mitochondria in cells comprise a tubulovesicular reticulum shaped by dynamic
      fission and fusion events. The multimeric dynamin-like GTPase Drp1 is a critical
      protein mediating mitochondrial division. It harbors multiple motifs including
      GTP-binding, middle, and GTPase effector (GED) domains that are important for
      both intramolecular and intermolecular interactions. As for other members of the
      dynamin superfamily, such interactions are critical for assembly of higher-order
      structures and cooperative increases in GTPase activity. Although the functions
      of Drp1 in cells have been extensively studied, mechanisms underlying its
      regulation remain less clear. Here, we have identified cAMP-dependent protein
      kinase-dependent phosphorylation of Drp1 within the GED domain at Ser(637) that
      inhibits Drp1 GTPase activity. Mechanistically, this change in GTPase activity
      likely derives from decreased interaction of GTP-binding/middle domains with the
      GED domain since the phosphomimetic S637D mutation impairs this intramolecular
      interaction but not Drp1-Drp1 intermolecular interactions. Using the
      phosphomimetic S637D substitution, we also demonstrate that mitochondrial fission
      is prominently inhibited in cells. Thus, protein phosphorylation at Ser(637)
      results in clear alterations in Drp1 function and mitochondrial morphology that
      are likely involved in dynamic regulation of mitochondrial division in cells.

PMID- 17553809
TI  - The Association of Physicians of Great Britain and Ireland: now what?

PMID- 17553810
TI  - Glomerular filtration rate estimation and mortality in an elderly population.
AB  - BACKGROUND: Few studies have addressed the link between minor renal dysfunction
      and mortality in the elderly. AIM: To compare three equations for estimated GFR
      (eGFR) in assessing renal dysfunction and predicting mortality in an elderly
      population. DESIGN: Longitudinal observational study. METHODS: We studied 441
      people from the Jerusalem Seventy Year Olds Longitudinal Study who had
      measurements of serum creatinine, all of whom were aged 70 years at study
      initiation and were living in the community. GFR was estimated based on serum
      creatinine and using the Cockcroft-Gault (CG), the abbreviated Modification of
      Diet in Renal Disease (MDRD) and the Mayo Clinic equations. Twelve-year mortality
      was the main outcome measure. RESULTS: The prevalence of reduced eGFR was 51%
      using the CG, 34% using MDRD and 16% using the Mayo Clinic equation. eGFR
      dichotomized by the definition of CKD significantly predicted mortality only with
      the Mayo Clinic equation (hazard ratio 1.56, 95%CI 1.01-2.39). When eGFR was
      divided into quartiles and the lowest compared to the highest, all equations
      predicted mortality. Hazard ratios (95%CI) were 5.48 (1.27-23.65), 7.47 (2.74
      20.3), and 7.375 (3.13-17.36), for CG, MDRD, and Mayo Clinic, respectively.
      DISCUSSION: Reduced eGFR was prevalent in this study group, and associated with
      mortality. This association was strongest using the Mayo Clinic equation.

PMID- 17553811
TI  - Health in all policies.

PMID- 17553812
TI  - Treating diabetic foot infections with sequential intravenous to oral
      moxifloxacin compared with piperacillin-tazobactam/amoxicillin-clavulanate.
AB  - OBJECTIVES: Complicated skin and skin structure infections (cSSSIs), including
      diabetic foot infections (DFIs), are often polymicrobial, requiring combination
      or broad-spectrum therapy. Moxifloxacin, a broad-spectrum fluoroquinolone, is
      approved for cSSSI and can be administered by either intravenous (iv) or oral
      routes. To assess the efficacy of moxifloxacin for treating DFIs, we analysed a
      subset of patients with these infections who were enrolled in a prospective,
      double-blind study that compared the efficacy of moxifloxacin with piperacillin
      tazobactam and amoxicillin-clavulanate. METHODS: Patients>or=18 years of age with
      a DFI requiring initial iv therapy were randomized to either moxifloxacin (400
      mg/day) or piperacillin-tazobactam (3.0/0.375 g every 6 h) for at least 3 days
      followed by moxifloxacin (400 mg/day orally) or amoxicillin-clavulanate (800 mg
      every 12 h orally), if appropriate, for 7-14 days. DFI was usually defined as any
      foot infection plus a history of diabetes. Our primary efficacy outcome was the
      clinical response of the infection at test-of-cure (TOC), 10-42 days post
      therapy. RESULTS: Among 617 patients enrolled in the original study, 78 with DFIs
      were evaluable for treatment efficacy. Clinical cure rates at TOC were similar
      for moxifloxacin and piperacillin-tazobactam/amoxicillin-clavulanate (68% versus
      61%) for patients with investigator-defined infection (P=0.54). Overall pathogen
      eradication rates in the microbiologically-valid population were 69% versus 66%
      for moxifloxacin and comparator, respectively (P=1.00). CONCLUSIONS:
      Intravenous+/-oral moxifloxacin was as effective as iv piperacillin-tazobactam+/
      amoxicillin-clavulanate in treating moderate-to-severe DFIs. Moxifloxacin may
      have potential as a monotherapy regimen for DFIs.

PMID- 17553813
TI  - Antifungal susceptibility of Cryptococcus neoformans and Cryptococcus gattii
      isolates from decayed wood of trunk hollows of Ficus religiosa and Syzygium
      cumini trees in north-western India.
AB  - BACKGROUND: We present antifungal susceptibility data on environmental isolates
      of Cryptococcus neoformans (serotype A, n=117) and Cryptococcus gattii (serotype
      B, n=65) cultured from decayed wood of trunk hollows of Ficus religiosa and
      Syzygium cumini trees. METHODS: Susceptibilities to amphotericin B, fluconazole,
      ketoconazole, itraconazole and voriconazole were determined by using Etest. The
      MICs were read after 48 h as per the guidelines provided by the manufacturer.
      RESULTS: The MIC90s and susceptibility ranges for C. neoformans isolates were as
      follows: 0.094 (0.004-0.25) mg/L for amphotericin B, 4 (0.032-12) mg/L for
      fluconazole, 0.094 (0.004-0.75) mg/L for itraconazole, 0.064 (0.002-0.19) mg/L
      for ketoconazole, and 0.047 (0.006-0.125) mg/L for voriconazole, whereas for C.
      gattii isolates these were 0.125 (0.023-0.5) mg/L for amphotericin B, 8 (0.032
      16) mg/L for fluconazole, 0.75 (0.006-2) mg/L for itraconazole, 0.125 (0.003
      0.19) mg/L for ketoconazole, and 0.094 (0.004-0.125) mg/L for voriconazole. A
      comparison of the geometric means of MICs (mg/L) revealed that C. gattii was less
      susceptible than C. neoformans to amphotericin B (0.075 versus 0.051, P=0.0003),
      fluconazole (2.912 versus 2.316, P=0.003), itraconazole (0.198 versus 0.0344,
      P<0.0001), ketoconazole (0.072 versus 0.037, P<0.0001), and voriconazole (0.045
      versus 0.023, P<0.0001). CONCLUSIONS: The antifungal susceptibility data obtained
      in this study indicate that the occurrence of primary resistance among
      environmental isolates of C. neoformans serotype A and C. gattii serotype B is
      rare, and serotype B isolates are less susceptible than serotype A isolates.

PMID- 17553814
TI  - Retinoic acid pathway genes show significantly altered expression in uterine
      fibroids when compared with normal myometrium.
AB  - Fibroids are benign neoplasms of myometrial smooth muscle cells (SMC). Despite
      being the most common tumor in humans, their etiology is poorly understood.
      Recent microarray studies have demonstrated that multiple members of the retinoid
      pathway are differentially expressed between myometrium and fibroids. The aim of
      this present study was to investigate gene expression of members of the retinoid
      pathway in matched myometrium and fibroids. We have demonstrated differential
      gene expression of two binding proteins [cellular retinol-binding proteins (CRBP)
      1 and 2], three enzymes [alcohol dehydrogenase 1 (ADH1), aldehyde dehydrogenase
      (ALDH1) and retinol dehydrogenase (RODH)] and two receptors [retinoid X receptors
      (RXR) alpha and gamma] involved in the retinoid pathway by real-time PCR. There
      were no differences in gene expression for retinoid receptors RARalpha, beta,
      gamma and RXRbeta, and for the metabolizing enzyme cytochrome P450, family 26
      subfamily A. We confirmed results for ADH1, ALDH1, CRBP1 and CRABP2 at the
      protein level by western blot. Using immunohistochemistry these proteins were
      mostly localized to myometrial and fibroid SMC. An exception to this was ALDH1
      protein, which displayed strong staining localized to cells of the connective
      tissue, presumably fibroblasts, with a striking differential expression pattern
      between myometrium and fibroids. These results demonstrate that the retinoid
      pathway is altered in fibroids when compared with normal myometrium and
      specifically identify ALDH1 in fibroid fibroblasts. These alterations can lead to
      aberrant retinoic acid (RA) production and signaling, and alter the expression of
      RA target genes, which may be an important step in fibroid development.

PMID- 17553815
TI  - Proton beam therapy for hepatocellular carcinoma with inferior vena cava tumor
      thrombus: report of three cases.
AB  - Three patients with hepatocellular carcinoma (HCC) and inferior vena cava tumor
      thrombus (IVCTT) were treated using proton beam therapy at the University of
      Tsukuba, Japan. A total dose of 50-70 Gy in 10-35 fractions was given to the
      primary tumor and IVCTT. All the patients survived for more than 1 year from the
      beginning of proton beam therapy (13-55 months) and no treatment-related toxicity
      of grade 3 or higher was observed. These cases suggest that proton beam therapy
      is safe and effective for patients with HCC associated with IVCTT.

PMID- 17553816
TI  - Relation of body mass index (BMI) to disease free (DFS) and distant disease free
      survivals (DDFS) among Turkish women with operable breast carcinoma.
AB  - BACKGROUND: The correlation between body mass index (BMI) and patient and tumor
      characteristics related to prognosis has not been well explored and may help to
      elucidate the mechanisms involved in the carcinogenesis. Because of the
      equivocal, inconsistent and uncertain research results as well as racial and
      ethnic differences, we aimed to evaluate the prognostic significance of high BMI
      in Turkish women with operable breast carcinoma. METHODS: Two hundred and sixty
      six patients who had operable invasive breast carcinoma diagnosed from 2000
      through 2004 in a single institution were evaluated for their demographic
      features, BMI, histopathological/immunohistochemical examinations and treatments.
      Quetelet BMI [weight (kg)/height (m)2] categories were selected according to the
      World Health Organization definition. Disease free survival (DSF) as well as
      distant disease free survival (DDSF) analyses were performed to identify
      independent prognostic factors. RESULTS: Post-menopausal patients were
      significantly in the higher quartile of BMI than pre-menopausal patients (P =
      0.003). While post-menopausal obese patients had worse DSF and DDFS (P = 0.001),
      vascular invasion was the independent prognostic factor for both survival indices
      (P = 0.031). CONCLUSIONS: Post-menopausal obese Turkish women are at increased
      risk of developing breast tumors with aggressive phenotype and obesity is a
      strong predictor of poor DSF and DDFS. Preventive strategies to reduce not only
      the prevalence of obesity and breast cancer but also the mortality must be
      recognized as the cost-effective public-health policy for Turkey.

PMID- 17553817
TI  - Which is the better pathological prognostic factor, the Nottingham histological
      grade or the Japanese nuclear grade? A large scale study with a long-term follow
      up.
AB  - BACKGROUND: We compared the Nottingham histological grade (H-grade) and the
      Japanese nuclear grade (N-grade) to select the better prognostic factor for
      breast cancers. METHODS: The series included 1786 patients with breast cancers
      with the exception of non-invasive and stage 4 cancers. They were classified
      according to the H- and N-grade. We analyzed their survival curves and also
      performed multivariate Cox regression analyses. RESULTS: According to the H-grade
      classification, 476 cases were grade 1, 647 cases were grade 2 and 663 cases were
      grade 3. According to the N-grade, 381 cases were grade 1, 215 cases were grade
      2, and 1129 cases were grade 3. In the survival curves of those cases with lymph
      node metastases (N+) and recurrent cases, there were statistically significant
      differences in different categories of the H-grades, but not in the N-grades. The
      survival curves of all the cases and those cases without lymph node metastases (N
      ) always exhibited statistically significant differences. According to the 2003
      St Gallen consensus, the N- group was classified as a minimal risk and an average
      risk groups. Both H- and N-grade exhibited statistically significant differences
      between the minimal risk and the average risk groups in the disease-free
      survival. The multivariate analyses proved that the H-grade was a statistically
      significant prognostic factor in all the cases and N+ group, but the N-grade was
      not significant in any of the studies. CONCLUSIONS: The H-grade is clearly proved
      to be a more significant prognostic factor for wider stage cases than the N
      grade.

PMID- 17553818
TI  - Magnetic resonance screening trial for hepatic metastasis in patients with
      locally controlled choroidal melanoma.
AB  - OBJECTIVE: The aim of the present study was to evaluate the value of magnetic
      resonance (MR) screening for detection of hepatic metastasis in patients with
      locally controlled choroidal melanoma. METHODS: MR examinations were performed
      after an initial diagnosis of choroidal melanoma in 159 patients (mean age 56
      years: range, 10-86 years). The MR follow-up interval was 5.2 +/- 1.7 years
      (range, 1.2-6.6 years). A total of 363 MR studies were reviewed by two
      radiologists for predominant signal intensity characteristics. Hepatic metastasis
      was verified by histological examination: tumor resection and CT-guided needle
      biopsy specimens and/or on the basis of an obvious progression in number and/or
      size of the lesions on the follow-up MR examination. RESULTS: The majority of
      patients underwent MR examinations from one to three times (n = 126, 79%). During
      a mean follow-up period of 5.7 years, a focal abnormality in the liver was found
      in 20 patients (13%). Of these, 15 patients (9%) were diagnosed as having hepatic
      metastasis. The number of the metastatic lesions with a short T1 and short T2
      pattern were one (n = 1, 9%), two (n = 2, 18%), three (n = 1, 9%) and multiple (n
      = 7, 63%). The focal abnormalities of MR examinations in five other patients
      consisted of vascular artifacts (n = 3, 15%) and cysts with hemorrhage (n = 2,
      10%). CONCLUSIONS: The screening of MR examinations detected hepatic metastasis
      in 15 of 159 patients (9%) with locally controlled choroidal melanoma.

PMID- 17553819
TI  - Effectiveness of hepatic resection for early-stage hepatocellular carcinoma in
      cirrhotic patients: subgroup analysis according to Milan criteria.
AB  - BACKGROUND: The aim of this study was to determine the long-term post-resection
      outcomes for cirrhotic patients with early-stage hepatocellular carcinoma (HCC).
      METHODS: A total of 217 < or = 65-year-old cirrhotic patients who underwent
      hepatic resection were divided into four groups in accordance with the Milan
      criteria: Group 1, those who met the Milan criteria (n = 130); Group 2A, those
      with a solitary tumor > 5 cm in size (n = 12); Group 2B, those with 2 or 3 tumors
      > 3 cm in size (n = 35); and Group 2C, those with > or = 4 tumors (n = 33).
      Overall and recurrence-free survival were compared between the groups. RESULTS:
      At 1, 3, 5 and 10 years, overall survival rates were 91, 67, 45 and 12%, and
      recurrence-free survival rates were 62, 26, 16 and 0%, respectively. Independent
      prognostic factors for overall survival were age, blood transfusion, tumor
      number, tumor size and microscopic vascular invasion; and for recurrence they
      were hepatitis C infection, tumor number, tumor size, microscopic vascular
      invasion and histological tumor grade. Group 1 patients had significantly better
      survival (5-year survival rate, 56%) than those of other groups (5-year survival
      rate, around 30%). The median tumor-free survival time was significantly shorter
      in Groups 2B and 2C (0.7 years and 0.6 years, respectively) than in Groups 1 and
      2A. CONCLUSIONS: Hepatic resection can confer a considerable overall survival
      benefit for cirrhotic patients with HCC who meet the Milan criteria. For patients
      with HCC who do not meet the criteria, however, hepatic resection has limited
      efficacy. We suggest that application of non-surgical therapy or expansion of the
      indications for liver transplantation may be warranted for such patient subsets.

PMID- 17553820
TI  - Pseudoaneurysm of the external carotid artery branch following radiotherapy for
      nasopharyngeal carcinoma.
AB  - Rupture of irradiated arteries in patients with head and neck cancer is an
      uncommon complication. We present the first case of a pseudoaneurysm of the
      external carotid artery branch that developed after irradiation of nasopharyngeal
      carcinoma and was successfully treated by microcoil embolization therapy.
      Clinicians should be aware of this unusual complication to avoid a potentially
      erroneous management.

PMID- 17553821
TI  - Prognostic and clinical evaluation of axillary lymph node metastasis in
      esophageal cancer.
AB  - Axillary lymph node metastasis (ALNM) from esophageal cancer is rare. Its
      prognosis and effective treatments remain unknown. Between 1997 and 2005,
      esophagectomy was performed in 361 patients with esophageal cancer in our
      hospital. ALNM was identified in four patients (1.1%). All patients had left ALNM
      with ipsilateral left supraclavicular lymph node metastasis. In two patients ALNM
      developed after radical esophagectomy with regional lymphadenectomy and in the
      other two patients after chemoradiotherapy of primary lesions. Axillary
      lymphadenectomy with chemoradiotherapy was given to all patients. Median survival
      time and disease-free survival (DFS) after initial treatment for primary
      esophageal cancer were 30.5 months and 11.5 months, respectively. One patient,
      who had a small number of regional lymph node metastases (two lymph nodes) at
      esophagectomy and prolonged DFS (22 months) until axillary node recurrence, is
      still alive, 67 months after axillary lymphadenectomy. The other three patients,
      who had larger numbers of regional lymph node metastases (average, 8.3) and
      shorter DFS (average, 9.7 months), died of recurrence an average of 13.3 months
      after axillary lymphadenectomy. In conclusion, although ALNM is considered a type
      of distant organ metastasis, if it is a solitary recurrence, good survival may be
      obtained after appropriate loco-regional therapy. The number of metastatic
      regional lymph nodes at initial esophagectomy and the duration of DFS until
      axillary node recurrence can help to guide the decision whether aggressive
      treatments are warranted.

PMID- 17553822
TI  - The Japan cancer surveillance report: incidence of childhood, bone, penis and
      testis cancers.

PMID- 17553823
TI  - A case of lung cancer showing widespread ground glass.

PMID- 17553824
TI  - Comparison of time trends in colorectal cancer incidence (1973-97) in East Asia,
      Europe and USA, from Cancer Incidence in Five Continents Vol. IV-VIII.

PMID- 17553825
TI  - Ability of bumblebees to discriminate differences in the shape of artificial
      flowers of Primula sieboldii (Primulaceae).
AB  - BACKGROUND AND AIMS: Flower shapes are important visual cues for pollinators.
      However, the ability of pollinators to discriminate between flower shapes under
      natural conditions is poorly understood. This study focused on the diversity of
      flower shape in Primula sieboldii and investigated the ability of bumblebees to
      discriminate between flowers by combining computer graphics with a traditional
      behavioural experiment. METHODS: Elliptic Fourier descriptors described shapes by
      transforming coordinate information for the contours into coefficients, and
      principal components analysis summarized these coefficients. Using these methods,
      artificial flowers were created based on the natural diversity of petal shape in
      P. sieboldii. Dual-choice tests were then performed to investigate the ability of
      the bumblebees to detect differences in the aspect ratio of petals and the depth
      of their head notch. KEY RESULTS: The insects showed no significant ability to
      detect differences in the aspect ratio of the petals under natural conditions
      unless the morphological distance increased to an unrealistic level. These
      results suggest the existence of a perception threshold for distances in this
      parameter. The bumblebees showed a significant preference for narrow petals even
      after training using flowers with wide petals. The bumblebees showed a
      significant ability to discriminate based on the depth of the petal head notch
      after training using artificial flowers with a deep head notch. However, they
      showed no discrimination in tests with training using extreme distances between
      flowers in this parameter. CONCLUSIONS: A new type of behavioural experiment was
      demonstrated using real variation in flower corolla shape in P. sieboldii. If the
      range in aspect ratios of petals expands much further, bumblebees may learn to
      exhibit selective behaviour. However, because discrimination by bumblebees under
      natural conditions was low, there may be no strong selective behaviour based on
      innate or learned preferences under natural conditions.

PMID- 17553826
TI  - Desiccation tolerance in the moss Polytrichum formosum: physiological and fine
      structural changes during desiccation and recovery.
AB  - BACKGROUND AND AIMS: This study explores basic physiological features and time
      relations of recovery of photosynthetic activity and CO2 uptake following
      rehydration of a desiccation-tolerant moss in relation to the full temporal
      sequence of cytological changes associated with recovery to the normal hydrated
      state. It seeks reconciliation of the apparently conflicting published
      physiological and cytological evidence on recovery from desiccation in
      bryophytes. METHODS: Observations were made of water-stress responses and
      recovery using infrared gas analysis and modulated chlorophyll fluorescence, and
      of structural and ultrastructural changes by light and transmission electron
      microscopy. KEY RESULTS: Net CO2 uptake fell to zero at approx. 40 % RWC,
      paralleling the fluorescence parameter PhiPSII at 200 micromol m(-2) s(-1) PPFD.
      On re-wetting the moss after 9-18 d desiccation, the initially negative net CO2
      uptake became positive 10-30 min after re-wetting, restoring a net carbon balance
      after approx. 0.3-1 h. The parameter Fv/Fm reached approx. 80 % of its pre
      desiccation value within approx. 10 min of re-wetting. In the presence of the
      protein-synthesis inhibitors chloramphenicol and cycloheximide, recovery of Fv/Fm
      (and CO2 exchange) proceeded normally in the dark, but declined rapidly in the
      light. Though initial recovery was rapid, both net CO2 uptake and Fv/Fm required
      approx. 24 h to recover completely to pre-desiccation values. The fixation
      protocols produced neither swelling of tissues nor plasmolysis. Thylakoids, grana
      and mitochondrial cristae remained intact throughout the drying-re-wetting cycle,
      but there were striking changes in the form of the organelles, especially the
      chloroplasts, which had prominent lobes and lamellar extensions in the normally
      hydrated state, but rounded off when desiccated, returning slowly to their normal
      state within approx. 24 h of re-wetting. Sub-cellular events during desiccation
      and re-wetting were generally similar to those seen in published data from the
      pteridophyte Selaginella lepidophylla. CONCLUSIONS: Initial recovery of
      respiration and photosynthesis (as of protein synthesis) is very rapid, and
      independent of protein synthesis, suggesting physical reactivation of systems
      conserved intact through desiccation and rehydration, but full recovery takes
      approx. 24 h. This is consistent with the cytological evidence, which shows the
      thylakoids and cristae remaining intact through the whole course of dehydration
      and rehydration. Substantial and co-ordinated changes in other cell components,
      which must affect spatial relationships of organelles and metabolic systems,
      return to normal on a time span similar to full recovery of photosynthesis.
      Comparison of the present data with recently published results suggests a
      significant role for the cytoskeleton in desiccation responses.

PMID- 17553827
TI  - The selenoproteome exhibits widely varying, tissue-specific dependence on
      selenoprotein P for selenium supply.
AB  - Selenoprotein P (Sel P) is a selenium-rich glycoprotein believed to play a key
      role in selenium (Se) transport throughout the body. Development of a Sel P
      knockout mouse model has supported this notion and initial studies have indicated
      that selenium supply to various tissues is differentially affected by genetic
      deletion of Sel P. Se in the form of the amino acid, selenocysteine, is
      incorporated into selenoproteins at UGA codons. Thus, Se availability affects not
      only selenoprotein levels, but also the turnover of selenoprotein mRNAs via the
      nonsense-mediated decay pathway. We investigated how genetic deletion of Sel P in
      mice affected levels of the mRNAs encoding all known members of the murine
      selenoprotein family, as well as three non-selenoprotein factors involved in
      their synthesis, selenophosphate synthetase 1 (SPS1), SECIS-binding protein 2
      (SBP2) and SECp43. Our findings present a comprehensive description of
      selenoprotein mRNA expression in the following murine tissues: brain, heart,
      intestine, kidney, liver, lung, spleen and testes. We also describe how abundance
      of selenoproteins and selenoprotein-synthesis factors are affected by genetic
      deletion of Sel P in some of these tissues, providing insight into how the
      presence of this selenoprotein influences selenoprotein mRNA levels, and thus,
      the selenoproteome.

PMID- 17553828
TI  - The Multi-Q web server for multiplexed protein quantitation.
AB  - The Multi-Q web server provides an automated data analysis tool for multiplexed
      protein quantitation based on the iTRAQ labeling method. The web server is
      designed as a platform that can accommodate various input data formats from
      search engines and mass spectrometer manufacturers. Compared to the previous
      stand-alone version, the new web server version provides many enhanced features
      and flexible options for quantitation. The workflow of the web server is
      represented by a quantitation wizard so that the tool is easy to use. It also
      provides a friendly interface that helps users configure their parameter settings
      before running the program. The web server generates a standard report for
      quantitation results. In addition, it allows users to customize their output
      reports and information of interest can be easily highlighted. The output also
      provides visualization of mass spectral data so that users can conveniently
      validate the results. The Multi-Q web server is a fully automated and easy to use
      quantitation tool that is suitable for large-scale multiplexed protein
      quantitation. Users can download the Multi-Q Web Server from
      http://ms.iis.sinica.edu.tw/Multi-Q-Web.

PMID- 17553829
TI  - siteFiNDER|3D: a web-based tool for predicting the location of functional sites
      in proteins.
AB  - Although knowledge of a protein's functional site is a key requirement for
      understanding its mode of action at the molecular level, our ability to locate
      such sites experimentally is far exceeded by the rate at which sequence and
      structural information is being accumulated. siteFiNDER|3D is an online tool for
      the prediction of functionally important regions in proteins of known structure.
      At the core of the server lies the CFG analysis algorithm, which uses a moving 3D
      window to correlate patterns of functional/chemical group conservation in the
      query protein with the location of functional sites. Here, we give a general
      overview of the functionality offered by the siteFiNDER|3D server, along with
      general recommendations aimed at maximizing the accuracy and predictive value of
      this tool in a variety of contexts. siteFiNDER|3D can be accessed at:
      'http://sage.csb.yale.edu/sitefinder3d' and requires, at a minimum, the atomic
      coordinates of a query protein in PDB format.

PMID- 17553831
TI  - Quantitative multiplexing analysis of PCR-amplified ribosomal RNA genes by
      hierarchical oligonucleotide primer extension reaction.
AB  - A method, termed hierarchical oligonucleotide primer extension (HOPE), is
      developed for quantitative, multiplexing detection of DNA targets present in PCR
      amplified community 16S rRNA genes. It involves strand extension reaction and
      multiple oligonucleotide primers modified with different lengths of polyA at the
      5' end and targeting 16S rRNA genes at different phylogenetic specificities. On
      annealing to the targets, these primers are extended with a single fluorescently
      labeled dideoxynucleoside triphosphate or a dye-terminator. Using a DNA
      autosequencer, these extended primers are separated and identified by size and
      dye color, and quantified and normalized based on the fluorescence intensities
      and internal size standards. Using a primer-to-target ratio >1000, constant
      primer extension efficiencies can be obtained with individual primers to
      establish a 'calibration factor' between individual primers and a universal or
      domain-specific primer, providing the relative abundance of targeted rRNA genes
      with respect to total rRNA genes. HOPE up to 10-plexing is demonstrated to
      correctly identify 20 different bacterial strains, and quantify different
      Bacteroides spp. in 16S rRNA gene amplicons from different model bacteria
      mixtures and the influent and effluent of a wastewater treatment plant. Single
      mismatch discrimination with detection sensitivity of a target down to 0.01-0.05%
      of total DNA template is achieved.

PMID- 17553830
TI  - Effects of nucleoid proteins on DNA repression loop formation in Escherichia
      coli.
AB  - The intrinsic stiffness of DNA limits its ability to be bent and twisted over
      short lengths, but such deformations are required for gene regulation. One
      classic paradigm is DNA looping in the regulation of the Escherichia coli lac
      operon. Lac repressor protein binds simultaneously to two operator sequences
      flanking the lac promoter. Analysis of the length dependence of looping-dependent
      repression of the lac operon provides insight into DNA deformation energetics
      within cells. The apparent flexibility of DNA is greater in vivo than in vitro,
      possibly because of host proteins that bind DNA and induce sites of flexure. Here
      we test DNA looping in bacterial strains lacking the nucleoid proteins HU, IHF or
      H-NS. We confirm that deletion of HU inhibits looping and that quantitative
      modeling suggests residual looping in the induced operon. Deletion of IHF has
      little effect. Remarkably, DNA looping is strongly enhanced in the absence of H
      NS, and an explanatory model is proposed. Chloroquine titration, psoralen
      crosslinking and supercoiling-sensitive reporter assays show that the effects of
      nucleoid proteins on looping are not correlated with their effects on either
      total or unrestrained supercoiling. These results suggest that host nucleoid
      proteins can directly facilitate or inhibit DNA looping in bacteria.

PMID- 17553832
TI  - 'In-line attack' conformational effect plays a modest role in an enzyme-catalyzed
      RNA cleavage: a free energy simulation study.
AB  - Since the proposal of 'in-line attack' conformation as a possibly important
      intermediate in RNA cleavage, its structure has been captured in various protein
      and RNA enzymes; these structures strengthen the belief that this conformation
      plays an essential role in the catalysis of RNA cleavage. As generally discussed,
      this intermediate structure can be involved in energy barrier reduction in two
      possible ways, e.g. through either conformational effect or electrostatic effect.
      In order to quantitatively elucidate the contribution of conformational effect in
      this type of enzyme catalysis, free energy simulations were performed on the RNA
      structures both in a splicing endonuclease complex and in the aqueous solution.
      Our free energy simulation results revealed that the 'in-line attack'
      conformational effect plays a modest role in facilitating the reaction rate
      enhancement (approximately 12-fold) compared with the overall 10(12)-fold rate
      increase. The close agreement between the present computational estimation and an
      experimental measurement on the spontaneous RNA cleavage in an in vitro evolved
      ATP aptamer motives us to realize that the conformation distribution of an enzyme
      substrate prior to rather than after its binding determines the upper bound of
      the rate enhancement ability through the conformational strategy.

PMID- 17553833
TI  - DOMAC: an accurate, hybrid protein domain prediction server.
AB  - Protein domain prediction is important for protein structure prediction,
      structure determination, function annotation, mutagenesis analysis and protein
      engineering. Here we describe an accurate protein domain prediction server
      (DOMAC) combining both template-based and ab initio methods. The preliminary
      version of the server was ranked among the top domain prediction servers in the
      seventh edition of Critical Assessment of Techniques for Protein Structure
      Prediction (CASP7), 2006. DOMAC server and datasets are available at:
      http://www.bioinfotool.org/domac.html.

PMID- 17553834
TI  - A versatile computational pipeline for bacterial genome annotation improvement
      and comparative analysis, with Brucella as a use case.
AB  - We present a bacterial genome computational analysis pipeline, called GenVar. The
      pipeline, based on the program GeneWise, is designed to analyze an annotated
      genome and automatically identify missed gene calls and sequence variants such as
      genes with disrupted reading frames (split genes) and those with insertions and
      deletions (indels). For a given genome to be analyzed, GenVar relies on a
      database containing closely related genomes (such as other species or strains) as
      well as a few additional reference genomes. GenVar also helps identify gene
      disruptions probably caused by sequencing errors. We exemplify GenVar's
      capabilities by presenting results from the analysis of four Brucella genomes.
      Brucella is an important human pathogen and zoonotic agent. The analysis revealed
      hundreds of missed gene calls, new split genes and indels, several of which are
      species specific and hence provide valuable clues to the understanding of the
      genome basis of Brucella pathogenicity and host specificity.

PMID- 17553836
TI  - MiPred: classification of real and pseudo microRNA precursors using random forest
      prediction model with combined features.
AB  - To distinguish the real pre-miRNAs from other hairpin sequences with similar stem
      loops (pseudo pre-miRNAs), a hybrid feature which consists of local contiguous
      structure-sequence composition, minimum of free energy (MFE) of the secondary
      structure and P-value of randomization test is used. Besides, a novel machine
      learning algorithm, random forest (RF), is introduced. The results suggest that
      our method predicts at 98.21% specificity and 95.09% sensitivity. When compared
      with the previous study, Triplet-SVM-classifier, our RF method was nearly 10%
      greater in total accuracy. Further analysis indicated that the improvement was
      due to both the combined features and the RF algorithm. The MiPred web server is
      available at http://www.bioinf.seu.edu.cn/miRNA/. Given a sequence, MiPred
      decides whether it is a pre-miRNA-like hairpin sequence or not. If the sequence
      is a pre-miRNA-like hairpin, the RF classifier will predict whether it is a real
      pre-miRNA or a pseudo one.

PMID- 17553835
TI  - Effects of nucleic acid local structure and magnesium ions on minus-strand
      transfer mediated by the nucleic acid chaperone activity of HIV-1 nucleocapsid
      protein.
AB  - HIV-1 nucleocapsid protein (NC) is a nucleic acid chaperone, which is required
      for highly specific and efficient reverse transcription. Here, we demonstrate
      that local structure of acceptor RNA at a potential nucleation site, rather than
      overall thermodynamic stability, is a critical determinant for the minus-strand
      transfer step (annealing of acceptor RNA to (-) strong-stop DNA followed by
      reverse transcriptase (RT)-catalyzed DNA extension). In our system,
      destabilization of a stem-loop structure at the 5' end of the transactivation
      response element (TAR) in a 70-nt RNA acceptor (RNA 70) appears to be the major
      nucleation pathway. Using a mutational approach, we show that when the acceptor
      has a weak local structure, NC has little or no effect. In this case, the
      efficiencies of both annealing and strand transfer reactions are similar.
      However, when NC is required to destabilize local structure in acceptor RNA, the
      efficiency of annealing is significantly higher than that of strand transfer.
      Consistent with this result, we find that Mg2+ (required for RT activity)
      inhibits NC-catalyzed annealing. This suggests that Mg2+ competes with NC for
      binding to the nucleic acid substrates. Collectively, our findings provide new
      insights into the mechanism of NC-dependent and -independent minus-strand
      transfer.

PMID- 17553837
TI  - MultiPhyl: a high-throughput phylogenomics webserver using distributed computing.
AB  - With the number of fully sequenced genomes increasing steadily, there is greater
      interest in performing large-scale phylogenomic analyses from large numbers of
      individual gene families. Maximum likelihood (ML) has been shown repeatedly to be
      one of the most accurate methods for phylogenetic construction. Recently, there
      have been a number of algorithmic improvements in maximum-likelihood-based tree
      search methods. However, it can still take a long time to analyse the
      evolutionary history of many gene families using a single computer. Distributed
      computing refers to a method of combining the computing power of multiple
      computers in order to perform some larger overall calculation. In this article,
      we present the first high-throughput implementation of a distributed
      phylogenetics platform, MultiPhyl, capable of using the idle computational
      resources of many heterogeneous non-dedicated machines to form a phylogenetics
      supercomputer. MultiPhyl allows a user to upload hundreds or thousands of amino
      acid or nucleotide alignments simultaneously and perform computationally
      intensive tasks such as model selection, tree searching and bootstrapping of each
      of the alignments using many desktop machines. The program implements a set of 88
      amino acid models and 56 nucleotide maximum likelihood models and a variety of
      statistical methods for choosing between alternative models. A MultiPhyl
      webserver is available for public use at:
      http://www.cs.nuim.ie/distributed/multiphyl.php.

PMID- 17553838
TI  - Functional genetic selection of Helix 66 in Escherichia coli 23S rRNA identified
      the eukaryotic-binding sequence for ribosomal protein L2.
AB  - Ribosomal protein L2 is a highly conserved primary 23S rRNA-binding protein. L2
      specifically recognizes the internal bulge sequence in Helix 66 (H66) of 23S rRNA
      and is localized to the intersubunit space through formation of bridge B7b with
      16S rRNA. The L2-binding site in H66 is highly conserved in prokaryotic
      ribosomes, whereas the corresponding site in eukaryotic ribosomes has evolved
      into distinct classes of sequences. We performed a systematic genetic selection
      of randomized rRNA sequences in Escherichia coli, and isolated 20 functional
      variants of the L2-binding site. The isolated variants consisted of eukaryotic
      sequences, in addition to prokaryotic sequences. These results suggest that
      L2/L8e does not recognize a specific base sequence of H66, but rather a
      characteristic architecture of H66. The growth phenotype of the isolated variants
      correlated well with their ability of subunit association. Upon continuous
      cultivation of a deleterious variant, we isolated two spontaneous mutations
      within domain IV of 23S rRNA that compensated for its weak subunit association,
      and alleviated its growth defect, implying that functional interactions between
      intersubunit bridges compensate ribosomal function.

PMID- 17553839
TI  - iPDA: integrated protein disorder analyzer.
AB  - This article presents a web server iPDA, which aims at identifying the disordered
      regions of a query protein. Automatic prediction of disordered regions from
      protein sequences is an important problem in the study of structural biology. The
      proposed classifier DisPSSMP2 is different from several existing disorder
      predictors by its employment of position-specific scoring matrices with respect
      to physicochemical properties (PSSMP), where the physicochemical properties
      adopted here especially take the disorder propensity of amino acids into account.
      The web server iPDA integrates DisPSSMP2 with several other sequence predictors
      in order to investigate the functional role of the detected disordered region.
      The predicted information includes sequence conservation, secondary structure,
      sequence complexity and hydrophobic clusters. According to the proportion of the
      secondary structure elements predicted, iPDA dynamically adjusts the cutting
      threshold of determining protein disorder. Furthermore, a pattern mining package
      for detecting sequence conservation is embedded in iPDA for discovering potential
      binding regions of the query protein, which is really helpful to uncovering the
      relationship between protein function and its primary sequence. The web service
      is available at http://biominer.bime.ntu.edu.tw/ipda and mirrored at
      http://biominer.cse.yzu.edu.tw/ipda.

PMID- 17553840
TI  - Elastic properties of ribosomal RNA building blocks: molecular dynamics of the
      GTPase-associated center rRNA.
AB  - Explicit solvent molecular dynamics (MD) was used to describe the intrinsic
      flexibility of the helix 42-44 portion of the 23S rRNA (abbreviated as Kt
      42+rGAC; kink-turn 42 and GTPase-associated center rRNA). The bottom part of this
      molecule consists of alternating rigid and flexible segments. The first flexible
      segment (Hinge1) is the highly anharmonic kink of Kt-42. The second one (Hinge2)
      is localized at the junction between helix 42 and helices 43/44. The rigid
      segments are the two arms of helix 42 flanking the kink. The whole molecule ends
      up with compact helices 43/44 (Head) which appear to be modestly compressed
      towards the subunit in the Haloarcula marismortui X-ray structure. Overall, the
      helix 42-44 rRNA is constructed as a sophisticated intrinsically flexible
      anisotropic molecular limb. The leading flexibility modes include bending at the
      hinges and twisting. The Head shows visible internal conformational plasticity,
      stemming from an intricate set of base pairing patterns including dynamical
      triads and tetrads. In summary, we demonstrate how rRNA building blocks with
      contrasting intrinsic flexibilities can form larger architectures with highly
      specific patterns of preferred low-energy motions and geometries.

PMID- 17553841
TI  - Alpha-catalytic subunits of 5'AMP-activated protein kinase display fiber-specific
      expression and are upregulated by chronic low-frequency stimulation in rat
      muscle.
AB  - 5'-AMP-activated protein kinase (AMPK) signaling initiates adaptive changes in
      skeletal muscle fibers that restore homeostatic energy balance. The purpose of
      this investigation was to examine, in rats, the fiber-type protein expression
      patterns of the alpha-catalytic subunit isoforms in various skeletal muscles, and
      changes in their respective contents within the tibialis anterior (TA) after
      chronic low-frequency electrical stimulation (CLFS; 10 Hz, 10 h daily), applied
      for 4 +/- 1.2 or 25 +/- 4.8 days. Immunocytochemical staining of soleus (SOL) and
      medial gastrocnemius (MG) showed that 86 +/- 4.1 to 97 +/- 1.4% of type IIA
      fibers stained for both the alpha1- and alpha2-isoforms progressively decreased
      to 63 +/- 12.2% of type IID/X and 9 +/- 2.4% of IIB fibers. 39 +/- 11.4% of IID/X
      and 83 +/- 7.9% of IIB fibers expressed only the alpha2 isoform in the MG, much
      of which was localized within nuclei. alpha1 and alpha2 contents, assessed by
      immunoblot, were lowest in the white gastrocnemius [WG; 80% myosin heavy chain
      (MHC) IIb; 20% MHCIId/x]. Compared with the WG, alpha1 content was 1.6 +/- 0.08
      (P < 0.001) and 1.8 +/- 0.04 (P < 0.0001)-fold greater in the red gastrocnemius
      (RG: 13%, MHCIIa) and SOL (21%, MHCIIa), respectively, and increased in
      proportion to MHCIIa content. Similarly, alpha2 content was 1.4 +/- 0.10 (P <
      0.02) and 1.5 +/- 0.07 (P < 0.001)-fold greater in RG and SOL compared with WG.
      CLFS induced 1.43 +/- 0.13 (P < 0.007) and 1.33 +/- 0.08 (P < 0.009)-fold
      increases in the alpha1 and alpha2 contents of the TA and coincided with the
      transition of faster type IIB and IID/X fibers toward IIA fibers. These findings
      indicate that fiber types differ with regard to their capacity for AMPK signaling
      and that this potential is increased by CLFS.

PMID- 17553842
TI  - Brain-derived neurotrophic factor in the ventromedial nucleus of the hypothalamus
      reduces energy intake.
AB  - Recent studies show that brain-derived neurotrophic factor (BDNF) decreases
      feeding and body weight after peripheral and ventricular administration. BDNF
      mRNA and protein, and its receptor TrkB, are widely distributed in the
      hypothalamus and other brain regions. However, there are few reports on specific
      brain sites of actions for BDNF. We evaluated the effect of BDNF, given into the
      ventromedial nucleus of the hypothalamus (VMH), on normal and deprivation- and
      neuropeptide Y (NPY)-induced feeding behavior and body weight. BDNF injected
      unilaterally or bilaterally into the VMH of food-deprived and nondeprived rats
      significantly decreased feeding and body weight gain within the 0- to 24-h and
      the 24- to 48-h postinjection intervals. Doses effectively producing inhibition
      of feeding behavior did not establish a conditioned taste aversion. BDNF-induced
      feeding inhibition was attenuated by pretreatment of the TrkB-Fc fusion protein
      that blocks binding between BDNF and its receptor TrkB. VMH-injected BDNF
      significantly decreased VMH NPY-induced feeding at 1, 2, and 4 h after injection.
      In summary, BDNF in the VMH significantly decreases food intake and body weight
      gain, by TrkB receptor-mediated actions. Furthermore, the anorectic effects of
      BDNF in this site appear to be mediated by NPY. These data suggest that the VMH
      is an important site of action for BDNF in its effects on energy metabolism.

PMID- 17553843
TI  - Long-term consequences of maternal high-fat feeding on hypothalamic leptin
      sensitivity and diet-induced obesity in the offspring.
AB  - Epidemiological and animal studies suggest that the alteration of hormonal and
      metabolic environment during fetal and neonatal development can contribute to
      development of metabolic syndrome in adulthood. In this paper, we investigated
      the impact of maternal high-fat (HF) diet on hypothalamic leptin sensitivity and
      body weight gain of offspring. Adult Wistar female rats received a HF or a
      control normal-fat (C) diet for 6 wk before gestation until the end of the
      suckling period. After weaning, pups received either C or HF diet during 6 wk.
      Body weight gain and metabolic and endocrine parameters were measured in the
      eight groups of rats formed according to a postweaning diet, maternal diet, and
      gender. To evaluate hypothalamic leptin sensitivity in each group, STAT-3
      phosphorylation was measured in response to leptin or saline intraperitoneal
      bolus. Pups exhibited similar body weights at birth, but at weaning, those born
      to HF dams weighed significantly less (-12%) than those born to C dams. When
      given the HF diet, males and females born to HF dams exhibited smaller body
      weight and feed efficiency than those born to C dams, suggesting increased energy
      expenditure programmed by the maternal HF diet. Thus, maternal HF feeding could
      be protective against adverse effects of the HF diet as observed in male
      offspring of control dams: overweight (+17%) with hyperleptinemia and
      hyperinsulinemia. Furthermore, offspring of HF dams fed either C or HF diet
      exhibited an alteration in hypothalamic leptin-dependent STAT-3 phosphorylation.
      We conclude that maternal high-fat diet programs a hypothalamic leptin resistance
      in offspring, which, however, fails to increase the body weight gain until
      adulthood.

PMID- 17553844
TI  - Atrial natriuretic peptide contribution to lipid mobilization and utilization
      during head-down bed rest in humans.
AB  - Head-down bed rest (HDBR) increases plasma levels of atrial natriuretic peptide
      (ANP) and decreases norepinephrine levels. We previously demonstrated that ANP
      promotes lipid mobilization and utilization, an effect independent of sympathetic
      nervous system activation, when infused into lean healthy men at pharmacological
      doses. The purpose of the present study was to demonstrate that a physiological
      increase in ANP contributes to lipid mobilization and oxidation in healthy young
      men. Eight men were positioned for 4 h in a sitting (control) or in a HDBR
      position. Indexes of lipid mobilization and hormonal changes were measured in
      plasma. Extracellular glycerol, an index of lipolysis, was determined in
      subcutaneous adipose tissue (SCAT) with a microdialysis technique. A twofold
      increase in plasma ANP concentration was observed after 60 min of HDBR, and a
      plateau was maintained thereafter. Plasma norepinephrine decreased by 30-40%
      during HDBR, while plasma insulin and glucose levels did not change. The level of
      plasma nonesterified fatty acids was higher during HDBR. SCAT lipolysis, as
      reflected by interstitial glycerol, as well as interstitial cGMP, the second
      messenger of the ANP pathway, increased during HDBR. This was associated with an
      increase in blood flow observed throughout HDBR. Significant changes in
      respiratory exchange ratio and percent use of lipid and carbohydrate were seen
      only after 3 h of HDBR. Thus the proportion of lipid oxidized increased by 40%
      after 3 h of HDBR. The rise in plasma ANP during HDBR was associated with
      increased lipolysis in SCAT and whole body lipid oxidation. In this physiological
      setting, independent of increasing catecholamines, our study suggests that ANP
      contributes to lipid mobilization and oxidation in healthy young men.

PMID- 17553845
TI  - Postnatal maturation attenuates pressure-evoked myogenic tone and stretch-induced
      increases in Ca2+ in rat cerebral arteries.
AB  - Although postnatal maturation potently modulates agonist-induced cerebrovascular
      contractility, its effects on the mechanisms mediating cerebrovascular myogenic
      tone remain poorly understood. Because the regulation of calcium influx and
      myofilament calcium sensitivity change markedly during early postnatal life, the
      present study tested the general hypothesis that early postnatal maturation
      increases the pressure sensitivity of cerebrovascular myogenic tone via age
      dependent enhancement of pressure-induced calcium mobilization and myofilament
      calcium sensitivity. Pressure-induced myogenic tone and changes in artery wall
      intracellular calcium concentrations ([Ca(2+)](i)) were measured simultaneously
      in endothelium-denuded, fura-2-loaded middle cerebral arteries (MCA) from pup
      [postnatal day 14 (P14)] and adult (6-mo-old) Sprague-Dawley rats. Increases in
      pressure from 20 to 80 mmHg enhanced myogenic tone in MCA from both pups and
      adults although the normalized magnitudes of these increases were significantly
      greater in pup than adult MCA. At each pressure step, vascular wall [Ca(2+)](i)
      was also significantly greater in pup than in adult MCA. Nifedipine significantly
      attenuated pressure-evoked constrictions in pup MCA and essentially eliminated
      all responses to pressure in the adult MCA. Both pup and adult MCA exhibited
      pressure-dependent increases in calcium sensitivity, as estimated by changes in
      the ratio of pressure-induced myogenic tone to wall [Ca(2+)](i). However, there
      were no differences in the magnitudes of these increases between pup and adult
      MCA. The results support the view that regardless of postnatal age, changes in
      both calcium influx and myofilament calcium sensitivity contribute to the
      regulation of cerebral artery myogenic tone. The greater cerebral myogenic
      response in P14 compared with adult MCA appears to be due to greater pressure
      induced increases in [Ca(2+)](i), rather than enhanced augmentation of
      myofilament calcium sensitivity.

PMID- 17553846
TI  - The effects of salt-induced hypertension on alpha1-adrenoreceptor expression and
      cardiovascular physiology in the rainbow trout (Oncorhynchus mykiss).
AB  - Experiments were conducted on rainbow trout to determine the impact of dietary
      salt on arterial blood pressure. After 4-6 wk, fish fed a salt-enriched diet
      exhibited a 37% elevation of dorsal aortic pressure (from 23.8 +/- 1.2 to 32.6 +/
      1.4 mmHg) and an 18% increase in ventral aortic pressure (from 33.0 +/- 1.5 to
      38.9 +/- 1.3 mmHg). The hypertension presumably reflected the increase in cardiac
      output (from 31.0 +/- 0.8 to 36.4 +/- 2.2 ml.min(-1).kg(-1)) because systemic and
      branchial resistances were statistically unaltered by salt feeding. The chronic
      hypertension was associated with a decrease in the pressor responses of the
      systemic vasculature to catecholamines and hypercapnia in the salt-fed fish. The
      reduction in alpha-adrenergic responsiveness of the systemic vasculature is
      consistent with desensitization or loss of functional alpha-adrenoceptors (alpha
      ARs). In support of this idea, the salt-fed fish exhibited significantly
      decreased levels of alpha(1D)-AR mRNA in the dorsal aorta and the afferent (ABA)
      and efferent branchial arteries (EBA). In contrast, however, the results obtained
      from norepinephrine dose-response curves for EBA and ABA vascular rings in vitro
      did not provide evidence for loss of function of branchial artery alpha(1)-ARs in
      the salt-fed fish. Indeed, the EC(50) for the EBA norepinephrine dose-response
      curve was significantly reduced (from 3.75 x 10(-7) to 2.12 x 10(-7) M) in the
      salt-fed fish, indicating an increase in the binding affinity of the alpha(1)
      ARs.

PMID- 17553847
TI  - Effects on neurite outgrowth and cell survival of a secreted fibroblast growth
      factor binding protein upregulated during spinal cord injury.
AB  - The fibroblast growth factor binding protein (FGF-BP; GenBank accession no.
      NP_005121) is a secreted protein that mobilizes FGFs from the extracellular
      matrix, protects them from degradation, and enhances their biological activity.
      Several previous studies reported that FGF-BP is an early response gene
      upregulated during tissue repair processes including wound healing and
      atherogenesis. In this study we analyzed whether FGF-BP expression was impacted
      by spinal cord injury and could have an effect on neuronal cell viability.
      Immunohistochemical and in situ hybridization studies revealed a dramatic
      upregulation of FGF-BP protein and mRNA levels following unilateral hemisection
      and contusion injury of adult rat spinal cord. In spinal cord sections of
      laminectomized rats, increased FGF-BP expression was observed in the fibers and
      cell bodies ipsilateral to the lesion site but was absent in the uninjured spinal
      cord tissue contralateral to the lesion. Increased expression of FGF-BP was
      observed at all postinjury time points, examined with peak levels occurring at
      day 4, a time when injury-induced increased levels of FGF2 have also been
      reported to be maximal. Moreover, using PC12 cells as a neuronal model, we
      observed that exogenous FGF-BP increased the capacity of FGF2 to stimulate
      neurite outgrowth and to increase cell survival. At the molecular level, FGF-BP
      enhanced FGF2-induced protein tyrosine phosphorylation and AKT/PKB activation.
      Collectively, these results suggest that FGF-BP is an early response gene after
      spinal cord injury and that its upregulation in regenerating spinal cord tissue
      may provide a molecular mechanism for enhancing the initial FGF2-mediated
      neurotrophic effects occurring after such tissue damage.

PMID- 17553849
TI  - Diurnal protein expression in blood revealed by high throughput mass spectrometry
      proteomics and implications for translational medicine and body time of day.
AB  - Molecular gene cycling is useful for determining body time of day (BTOD) with
      important applications in personalized medicine, including cardiovascular disease
      and cancer, our leading causes of death. However, it impractically requires
      repetitive invasive tissue sampling that is obviously not applicable for humans.
      Here we characterize diurnal protein cycling in blood using high-throughput
      proteomics; blood proteins are easily accessible, minimally invasive, and can
      importantly serve as surrogates for what is happening elsewhere in the body in
      health and disease. As proof of the concept, we used normal C57BL/6 mice
      maintained under regular 24-h light and dark cycles. First, we demonstrated
      fingerprint patterns in 24-h plasma, revealed using surface-enhanced laser
      desorption and ionization (SELDI). Second, we characterized diurnal cycling
      proteins in blood using chromatography and tandem electrospray ionization mass
      spectrometry. Importantly, we noted little association between the cycling blood
      proteome and tissue transcriptome, delineating the necessity to identify de novo
      cycling proteins in blood for measuring BTOD. Furthermore, we explored known
      interaction networks to identify putative functional pathways regulating protein
      expression patterns in blood, thus shedding new light on our understanding of
      integrative physiology. These studies have profound clinical significance in
      translating the concept of BTOD to the practical realm for molecular diagnostics
      and open new opportunities for clinically relevant discoveries when applied to
      ELISA-based molecular testing and/or point-of-care devices.

PMID- 17553848
TI  - Altered basal and stimulated accumbens dopamine release in obese OLETF rats as a
      function of age and diabetic status.
AB  - The Otsuka Long-Evans Tokushima Fatty (OLETF) rat lacking the CCK-1 receptor is
      hyperphagic, prefers palatable and high-calorie meals, and gradually develops
      obesity and type 2 diabetes. To determine dopamine levels in this strain, we used
      in vivo quantitative (no net flux) microdialysis at three different ages
      representing nondiabetic (8 wk), prediabetic (18 wk), and diabetic (56 wk) stages
      in OLETF and age-matched lean Long-Evans Tokushima Otsuka (LETO) controls.
      Results showed significantly elevated basal dopamine levels in the caudomedial
      nucleus accumbens of OLETF rats compared with LETO at younger ages (8 wk: 20.10
      +/- 5.61 nM vs. 15.85 +/- 5.63 nM; 18 wk: 7.37 +/- 3.71 nM vs. 4.75 +/- 1.25 nM,
      means +/- SD). In contrast, at 56 wk of age, a profound decline in extracellular
      dopamine concentrations was seen in both strains with a tendency for a greater
      effect in OLETF rats (1.78 +/- 0.40 nM vs. 2.39 +/- 0.42 nM). Further,
      extracellular fraction, an index for reuptake, was higher in 56-wk-old OLETF
      compared with LETO (0.648 +/- 0.049 vs. 0.526 +/- 0.057). Potassium-stimulated
      dopamine efflux revealed an increased capacity of vesicular pool in OLETF rats
      compared with LETO across all age groups with an accentuated strain difference at
      56 wk. These findings demonstrate altered striatal dopamine functions (i.e.,
      increased stimulated release and uptake) in obese OLETF rat. This could be due to
      the lack of functional CCK-1 receptors, or metabolic and hormonal factors
      associated with the development of obesity and insulin resistance, or both.

PMID- 17553850
TI  - Impact of alpha1-adrenoceptor expression on contractile properties of vascular
      smooth muscle cells.
AB  - Low-frequency blood pressure oscillations (Mayer waves) are discussed as a marker
      for sympathetic modulation of vascular tone. However, the factors that determine
      the frequency response of the vasculature to sympathetic stimuli are not fully
      understood. Possible mechanisms include functions related to alpha(1)-adrenergic
      receptors (alpha(1)-AR) and postreceptor processes involved in the vascular
      contractile response. The purpose of the present study was to examine the
      hypothesis that expression levels of alpha(1)-AR and their subtype distribution
      determine velocity and magnitude of alpha(1)-AR-mediated vascular smooth muscle
      cell (VSMC) contraction. alpha(1A)-, alpha(1B)-, and alpha(1D)-AR subtypes were
      transfected into VSMCs from rat aorta and characterized immunocytochemically via
      confocal microscopy. Functional studies in isolated cells were performed using
      video microscopy. The alpha(1)-AR agonist phenylephrine produced dose-dependent
      contractions of VSMCs. All transfected groups were more sensitive to
      phenylephrine compared with controls. Maximal contraction velocity almost doubled
      in transfected cells. However, no differences in observed parameters were found
      between the three transfected groups. Contractile properties in response to
      membrane depolarization with KCl were similar in all groups. In conclusion,
      alpha(1)-AR density determines velocity and sensitivity of alpha(1)-AR-mediated
      contraction in VSMCs. alpha(1)-AR subtype distribution does not appear to
      influence vasoconstriction to sympathetic stimuli.

PMID- 17553851
TI  - Contributions of glucokinase and phosphofructokinase-2/fructose bisphosphatase-2
      to the elevated glycolysis in hepatocytes from Zucker fa/fa rats.
AB  - The insulin-resistant Zucker fa/fa rat has elevated hepatic glycolysis and
      activities of glucokinase and phosphofructokinase-2/fructose bisphosphatase-2
      (PFK2). The latter catalyzes the formation and degradation of fructose-2,6
      bisphosphate (fructose-2,6-P(2)) and is a glucokinase-binding protein. The
      contributions of glucokinase and PFK2 to the elevated glycolysis in fa/fa
      hepatocytes were determined by overexpressing these enzymes individually or in
      combination. Metabolic control analysis was used to determine enzyme coefficients
      on glycolysis and metabolite concentrations. Glucokinase had a high control
      coefficient on glycolysis in all hormonal conditions tested, whereas PFK2 had
      significant control only in the presence of glucagon, which phosphorylates PFK2
      and suppresses glycolysis. Despite the high control strength of glucokinase, the
      elevated glycolysis in fa/fa hepatocytes could not be explained by the elevated
      glucokinase activity alone. In hepatocytes from fa/fa rats, glucokinase
      translocation between the nucleus and the cytoplasm was refractory to glucose but
      responsive to glucagon. Expression of a kinase-active PFK2 variant reversed the
      glucagon effect on glucokinase translocation and glucose phosphorylation,
      confirming the role for PFK2 in sequestering glucokinase in the cytoplasm.
      Glucokinase had a high control on glucose-6-phosphate content; however, like
      PFK2, it had a relative modest effect on the fructose-2,6-P(2) content. However,
      combined overexpression of glucokinase and PFK2 had a synergistic effect on
      fructose-2,6-P(2) levels, suggesting that interaction of these enzymes may be a
      prerequisite for formation of fructose-2,6-P(2). Cumulatively, this study
      provides support for coordinate roles for glucokinase and PFK2 in the elevated
      hepatic glycolysis in fa/fa rats.

PMID- 17553852
TI  - A mechanistic approach to understanding conjugated linoleic acid's role in
      inflammation using murine models of rheumatoid arthritis.
AB  - A naturally occurring fatty acid, conjugated linoleic acid (CLA), reduces immune
      induced TNF and inducible cyclooxygenase (COX-2) expression; key mediators of
      inflammation in rheumatoid arthritis (RA). On the basis of previous work, it was
      hypothesized that dietary CLA would act as an anti-inflammatory agent in select
      animal models of RA. In the collagen antibody-induced arthritis (CAIA) model,
      mice fed CLA (mixed isomers of c9, t11, and t10, c12-CLA) for 3 wk before
      anticollagen antibody injection had reduced lipopolysaccharide-induced plasma TNF
      levels and had arthritic scores that were 60% of mice fed corn oil (CO). In the
      collagen-induced arthritis (CIA) model, mice fed mixed isomers of CLA for 21 days
      before immunization had lower IgG(1) titers, earlier signs of joint inflammation,
      but similar arthritis scores compared with CO fed mice during the remaining 70
      day post-injection period. Beginning on day 80 to 133, CLA-fed mice had arthritic
      scores 70% that of the CO-fed mice. In a second CIA experiment, CLA was fed only
      after the booster injection. Plasma IgG(1) levels were not reduced and arthritis
      onset was delayed 4 days in CLA-fed mice compared with the CO-fed mice. Peak
      arthritis score was similar between CLA and CO-fed mice from day 35 to 56.
      Because CLA reduced inflammation in the CAIA model, delayed onset of arthritis in
      the CIA model (CIA experiment 2) and reduced arthritis score after day 80 in the
      CIA model (CIA experiment 1), we concluded that dietary CLA exhibited anti
      inflammatory activity that was dependent on antibody.

PMID- 17553853
TI  - Significance analysis of groups of genes in expression profiling studies.
AB  - MOTIVATION: Gene class testing (GCT) is a statistical approach to determine
      whether some functionally predefined classes of genes express differently under
      two experimental conditions. GCT computes the P-value of each gene class based on
      the null distribution and the gene classes are ranked for importance in
      accordance with their P-values. Currently, two null hypotheses have been
      considered: the Q1 hypothesis tests the relative strength of association with the
      phenotypes among the gene classes, and the Q2 hypothesis assesses the statistical
      significance. These two hypotheses are related but not equivalent. METHOD: We
      investigate three one-sided and two two-sided test statistics under Q1 and Q2.
      The null distributions of gene classes under Q1 are generated by permuting gene
      labels and the null distributions under Q2 are generated by permuting samples.
      RESULTS: We applied the five statistics to a diabetes dataset with 143 gene
      classes and to a breast cancer dataset with 508 GO (Gene Ontology) terms. In each
      statistic, the null distributions of the gene classes under Q1 are different from
      those under Q2 in both datasets, and their rankings can be different too. We
      clarify the one-sided and two-sided hypotheses, and discuss some issues regarding
      the Q1 and Q2 hypotheses for gene class ranking in the GCT. Because Q1 does not
      deal with correlations among genes, we prefer test based on Q2. SUPPLEMENTARY
      INFORMATION: Supplementary data are available at Bioinformatics online.

PMID- 17553854
TI  - Systematic construction of gene coexpression networks with applications to human
      T helper cell differentiation process.
AB  - MOTIVATION: Coexpression networks have recently emerged as a novel holistic
      approach to microarray data analysis and interpretation. Choosing an appropriate
      cutoff threshold, above which a gene-gene interaction is considered as relevant,
      is a critical task in most network-centric applications, especially when two or
      more networks are being compared. RESULTS: We demonstrate that the performance of
      traditional approaches, which are based on a pre-defined cutoff or significance
      level, can vary drastically depending on the type of data and application.
      Therefore, we introduce a systematic procedure for estimating a cutoff threshold
      of coexpression networks directly from their topological properties. Both
      synthetic and real datasets show clear benefits of our data-driven approach under
      various practical circumstances. In particular, the procedure provides a robust
      estimate of individual degree distributions, even from multiple microarray
      studies performed with different array platforms or experimental designs, which
      can be used to discriminate the corresponding phenotypes. Application to human T
      helper cell differentiation process provides useful insights into the components
      and interactions controlling this process, many of which would have remained
      unidentified on the basis of expression change alone. Moreover, several human
      mouse orthologs showed conserved topological changes in both systems, suggesting
      their potential importance in the differentiation process. SUPPLEMENTARY
      INFORMATION: Supplementary data are available at Bioinformatics online.

PMID- 17553855
TI  - The commonality of protein interaction networks determined in neurodegenerative
      disorders (NDDs).
AB  - MOTIVATION: Neurodegenerative disorders (NDDs) are progressive and fatal
      disorders, which are commonly characterized by the intracellular or extracellular
      presence of abnormal protein aggregates. The identification and verification of
      proteins interacting with causative gene products are effective ways to
      understand their physiological and pathological functions. The objective of this
      research is to better understand common molecular pathogenic mechanisms in NDDs
      by employing protein-protein interaction networks, the domain characteristics
      commonly identified in NDDs and correlation among NDDs based on domain
      information. RESULTS: By reviewing published literatures in PubMed, we created
      pathway maps in Kyoto Encyclopedia of Genes and Genomes (KEGG) for the protein
      protein interactions in six NDDs: Alzheimer's disease (AD), Parkinson's disease
      (PD), amyotrophic lateral sclerosis (ALS), Huntington's disease (HD),
      dentatorubral-pallidoluysian atrophy (DRPLA) and prion disease (PRION). We also
      collected data on 201 interacting proteins and 13 compounds with 282 interactions
      from the literature. We found 19 proteins common to these six NDDs. These common
      proteins were mainly involved in the apoptosis and MAPK signaling pathways. We
      expanded the interaction network by adding protein interaction data from the
      Human Protein Reference Database and gene expression data from the Human Gene
      Expression Index Database. We then carried out domain analysis on the extended
      network and found the characteristic domains, such as 14-3-3 protein,
      phosphotyrosine interaction domain and caspase domain, for the common proteins.
      Moreover, we found a relatively high correlation between AD, PD, HD and PRION,
      but not ALS or DRPLA, in terms of the protein domain distributions. AVAILABILITY:
      http://www.genome.jp/kegg/pathway/hsa/hsa01510.html (KEGG pathway maps for NDDs).

PMID- 17553856
TI  - Characterization of mismatch and high-signal intensity probes associated with
      Affymetrix genechips.
AB  - MOTIVATION: For Affymetrix microarray platforms, gene expression is determined by
      computing the difference in signal intensities between perfect match (PM) and
      mismatch (MM) probesets. Although the use of PM is not controversial, MM
      probesets have been associated with variance and ultimately inaccurate gene
      expression calls. A principal focus of this study was to investigate the nature
      of the MM signal intensities and demonstrate its contribution to the experimental
      results. RESULTS: While most MM intensities were likely associated with random
      noise, a subset of approximately 20% (99,485) of the MM probes displayed
      relatively high signal intensities to the corresponding PM probes (MM > PM) in a
      non-random fashion; 13,440 of these probes demonstrated exceptionally high
      'outlier' intensities. About 15,938 PM probes also demonstrated exceptionally
      high outlier intensities consistently across all hybridizations. About 92% of the
      MM > PM probes had either a dThymidine (dT) or a dCytidine (dC) at the 13th
      position of the probe sequence. MM and PM probes displaying extremely high
      outlier intensities contained high dC rich nucleotides, and low dA contents at
      other nucleotides positions along the 25mer probe sequence. Differentially
      expressed genes generated using Genechip Operating System (GCOS) or modified PM
      only methods were also examined. Of those candidate genes identified in the PM
      only method, 157 of them were designated by GCOS as absent across all datasets
      and many others contained probes with MM > PM signal intensities. Our data
      suggests that MM intensity from PM signal can be a major source of error
      analysis, leading to fewer potentially biologically important candidate genes.
      SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics
      online.

PMID- 17553857
TI  - Predicting survival from microarray data--a comparative study.
AB  - MOTIVATION: Survival prediction from gene expression data and other high
      dimensional genomic data has been subject to much research during the last years.
      These kinds of data are associated with the methodological problem of having many
      more gene expression values than individuals. In addition, the responses are
      censored survival times. Most of the proposed methods handle this by using Cox's
      proportional hazards model and obtain parameter estimates by some dimension
      reduction or parameter shrinkage estimation technique. Using three well-known
      microarray gene expression data sets, we compare the prediction performance of
      seven such methods: univariate selection, forward stepwise selection, principal
      components regression (PCR), supervised principal components regression, partial
      least squares regression (PLS), ridge regression and the lasso. RESULTS:
      Statistical learning from subsets should be repeated several times in order to
      get a fair comparison between methods. Methods using coefficient shrinkage or
      linear combinations of the gene expression values have much better performance
      than the simple variable selection methods. For our data sets, ridge regression
      has the overall best performance. AVAILABILITY: Matlab and R code for the
      prediction methods are available at
      http://www.med.uio.no/imb/stat/bmms/software/microsurv/.

PMID- 17553858
TI  - The MiSink Plugin: Cytoscape as a graphical interface to the Database of
      Interacting Proteins.
AB  - The MiSink Plugin converts Cytoscape, an open-source bioinformatics platform for
      network visualization, to a graphical interface for the database of interacting
      proteins (DIP: http://dip.doe-mbi.ucla.edu). Seamless integration is possible by
      providing bi-directional communication between Cytoscape and any Web site
      supplying data in XML or tab-delimited format. AVAILABILITY: MiSink is freely
      available for download at http://dip.doe-mbi.ucla.edu/Software.cgi.

PMID- 17553859
TI  - Assessment of contributors to radiation dose following intakes of rapidly
      excreted [14C]-compounds.
AB  - The International Commission on Radiological Protection default biokinetic model
      for the assessment of radiation dose received following intakes of unspecified
      [14C]-compounds (DCM) appears to overestimate the radiation doses delivered by
      many [14C]-compounds. The DCM does not specify the route of elimination and this
      review of the biokinetic data for four [14C]-compounds, [14C]sevelamer,
      [14C]colestipol, [14C]levetiracetam and [14C]ifetroban, that are rapidly lost
      from the human body via different excretory pathways, indicates that the
      excretory pathway is the critical determinant for both the individual tissue
      doses and the effective dose. If there is significant faecal excretion the DCM
      does not overestimate the effective dose.

PMID- 17553860
TI  - Development of a voxel phantom of Japanese adult male in upright posture.
AB  - A Japanese voxel phantom in upright posture, JM2, has been developed on the basis
      of CT images of a healthy Japanese adult male. Body characteristics of JM2 were
      compared with those of the supine voxel phantom, JM, previously developed using
      CT images of the same person. Differences were found in the shapes of the spine
      and lower abdomen and the locations of several organs such as kidneys, liver and
      stomach between the two phantoms. Specific absorbed fractions (SAFs) for 24
      target and 11 sources organs were calculated for monoenergetic photon ranging
      from 0.01 to 4 MeV. It was found that the SAFs for the kidneys as source organ
      and the lower large intestine wall as target organ in JM2 were significantly
      higher than those in JM for all photon energies. The differences of the SAFs
      between the two phantoms were attributed to the differences in the organ distance
      and organ geometry depending on the posture.

PMID- 17553861
TI  - Percutaneous penetration of uranium in rats after a contamination on intact or
      wounded skin.
AB  - The aim of this work is to assess in vivo in a hairless rat model, the
      percutaneous diffusion of uranium through intact or wounded rat skin. Six types
      of wounds were simulated by excoriation and burns with 10 N HF, 2, 5 and 14 N
      HNO3 and 10 N NaOH on anaesthetised hairless rats. Percutaneous penetration
      through wounded skin towards blood and subsequent urinary excretion of uranium
      was followed in vivo during 24 h. The influence of the physicochemical form
      (solution or powder) of uranyl nitrate (UN) on its percutaneous diffusion was
      also investigated. UN, even as a powder, can diffuse through intact skin. The
      presence of uranium in blood is more persistent and its urinary elimination is
      slower after an HF burn than after an HNO3 burn. Excoriation increases
      dramatically percutaneous absorption of UN. Thus, percutaneous diffusion of UN is
      largely dependent on skin barrier integrity with a particular importance of
      stratum corneum.

PMID- 17553862
TI  - The autocorrelation coefficient as a tool for assessing goodness of fit between
      bioassay predictions and measurement data.
AB  - Project IDEAS has produced guidelines for internal dose assessment. An integral
      part of this process is assessing the goodness of fit of biokinetic models to
      bioassay data. It is recommended that a fit should only be accepted if (a) it is
      close enough to the data not to be rejected by a chi2 test and (b) if it looks
      acceptable to 'the eye'. The latter criterion was added to enable the assessor to
      reject fits which seemed to display some sort of systematic bias. However, there
      are problems with both of these tests: (a) the chi2 test is dependent on the
      assumed uncertainties which are often unknown, (b) 'by eye' assessment is
      subjective. In this paper, another statistic, the autocorrelation coefficient of
      the residuals, rho, is investigated. The main advantages of the rho statistic are
      that it is objective, very sensitive to biasing and independent of the assumed
      errors.

PMID- 17553863
TI  - Measurement of the spectral fluence rate of reference neutron sources with a
      liquid scintillation detector.
AB  - Reference neutron sources such as (241)AmBe(alpha,n) and (252)Cf are commonly
      used to calibrate neutron detectors for radiation protection purposes. The
      calibration factors of these detectors depend on the spectral distribution of the
      neutron fluence from the source. Differences between the spectral fluence of the
      neutron source and the ISO-recommended reference spectra might be caused by the
      properties of the individual source. The spectral neutron fluence rates of
      different reference neutron sources used at PTB were measured with a liquid
      scintillation detector (NE213), using maximum entropy unfolding and a new,
      experimentally determined detector response matrix. The detector response matrix
      was determined by means of the time-of-flight technique at a pulsed neutron
      source with a broad energy distribution realised at the PTB accelerator facility.
      The results of the measurements of the reference sources are compared with the
      ISO-recommended reference spectra. For the PTB (241)AmBe(alpha,n) reference
      source, the spectral neutron fluence was determined by means of a high-resolution
      (3)He semiconductor sandwich spectrometer in 1982. These measurements were the
      basis for the ISO recommendations. The current measurements confirm the high
      energy part (E(n) > 2 MeV) of this spectrum and demonstrate the suitability of
      this new method for high-resolution spectrometry of broad neutron spectra.

PMID- 17553864
TI  - Improvements in routine internal monitoring--an overview of the IDEA project.
AB  - The IDEA project aimed to improve the assessment of incorporated radionuclides
      through developments of advanced in vivo and bioassay monitoring techniques and
      making use of such enhancements for improvements in routine monitoring. Many of
      these findings are not new in the sense that they are being already employed in
      advanced laboratories or for specialised applications. The primary goal was to
      categorise those new developments regarding their potential and eligibility for
      the routine monitoring community. Attention has been given to in vivo monitoring
      techniques with respect to detector characteristics and measurement geometry to
      improve measurement efficiency with special attention to low energy gamma
      emitters. Calibration-specifically supported by or through methods of numerical
      simulation-have been carefully analysed to reduce overall measurement
      uncertainties and explore ways to accommodate the individual variability based on
      characteristic features of a given person. For bioassay measurements at low
      detection limits, inductively coupled plasma mass spectroscopy offers significant
      advantages both in accuracy, speed, and sample preparation. Specifically, the
      determination of U and Th in urine and the associated models have been
      investigated. Finally, the scientific achievements have been analysed regarding
      their potential to offer benefits for routine monitoring. These findings will be
      presented in greater detail in other papers at this conference, whereas this
      paper intends to give an overview and put both the scientific achievements as
      well as the derived benefits into perspective.

PMID- 17553865
TI  - A specific voxel phantom for in vivo measurements of 241Am in the knee.
AB  - Calibration phantoms for in vivo measurements of low-energy photons should be
      anatomically realistic to minimise the uncertainties in the activity assessment.
      The calibration of the detection system can be performed using computational
      techniques based on numerical phantoms. The purpose of this work is to approach a
      numerical calibration by Monte Carlo (MC) technique of a Germanium detection
      system for the determination of 241Am in the knee. A specific voxel phantom was
      built from a computerised tomography of the calibration Spitz knee phantom. The
      phantom and the procedure to generate the associated input file for the MC code,
      namely MCNPX, have been described, as well as the characterisation of the
      detectors according to the manufacturer data and the energy calibration curves of
      the spectrometer. The detection efficiency and the pulse-height distribution have
      been determined for a homogeneous contamination of 241Am in bone.

PMID- 17553866
TI  - Monte Carlo evaluated parameters for internal dosimetry.
AB  - The radiation doses received by individuals from radionuclides which enter the
      human body cannot be measured directly but must be inferred. In these
      calculations, several measurable quantities (such as the internal whole body
      burden or urine daily excretion) and quantities derived from models are employed.
      The Radiation Protection Quantities for internal dosimetry are, in principle, the
      same as for external dosimetry with the addition of quantities taking into
      account that the doses in the body are protracted. Other parameters are also
      necessary for the dose assessment, such as the SAFs (Specific Absorbed
      Fractions). All these quantities are calculated using Monte Carlo codes and
      complex anthropomorphic phantoms. Monte Carlo codes are also widely employed as
      useful tools during the calibration procedure for in vivo measurements. This
      paper summarises the role played by Monte Carlo modelling in these fields.

PMID- 17553867
TI  - Development of smallpox vaccine candidates with integrated interleukin-15 that
      demonstrate superior immunogenicity, efficacy, and safety in mice.
AB  - The potential use of variola virus, the etiological agent of smallpox, as a
      bioterror agent has heightened the interest in the reinitiation of smallpox
      vaccination. However, the currently licensed Dryvax vaccine, despite its
      documented efficacy in eradicating smallpox, is not optimal for the vaccination
      of contemporary populations with large numbers of individuals with
      immunodeficiencies because of severe adverse effects that can occur in such
      individuals. Therefore, the development of safer smallpox vaccines that can match
      the immunogenicity and efficacy of Dryvax for the vaccination of contemporary
      populations remains a priority. Using the Wyeth strain of vaccinia virus derived
      from the Dryvax vaccine, we generated a recombinant Wyeth interleukin-15 (IL-15)
      with integrated IL-15, a cytokine with potent immunostimulatory functions. The
      integration of IL-15 into the Wyeth strain resulted in a >1,000-fold reduction in
      lethality of vaccinated athymic nude mice and induced severalfold-higher cellular
      and humoral immune responses in wild-type mice that persisted longer than those
      induced by the parental Wyeth strain. The superior efficacy of Wyeth IL-15 was
      further demonstrated by the ability of vaccinated mice to fully survive a lethal
      intranasal challenge of virulent vaccinia virus even 10 months after vaccination,
      whereas all mice vaccinated with parental Wyeth strain succumbed. By integrating
      IL-15 into modified vaccinia virus Ankara (MVA), a virus currently under
      consideration as a substitute for the Dryvax vaccine, we developed a second
      vaccine candidate (MVA IL-15) with greater immunogenicity and efficacy than
      Dryvax. Thus, Wyeth IL-15 and MVA IL-15 viruses hold promise as more-efficacious
      and safe alternatives to the Dryvax vaccine.

PMID- 17553868
TI  - Proline 35 of human immunodeficiency virus type 1 (HIV-1) Vpr regulates the
      integrity of the N-terminal helix and the incorporation of Vpr into virus
      particles and supports the replication of R5-tropic HIV-1 in human lymphoid
      tissue ex vivo.
AB  - Mutational analysis of the four conserved proline residues in human
      immunodeficiency virus type 1 (HIV-1) Vpr reveals that only Pro-35 is required
      for efficient replication of R5-tropic, but not of X4-tropic, viruses in human
      lymphoid tissue (HLT) cultivated ex vivo. While Vpr-mediated apoptosis and G(2)
      cell cycle arrest, as well as the expression and subcellular localization of Vpr,
      were independent, the capacity for encapsidation of Vpr into budding virions was
      dependent on Pro-35. (1)H nuclear magnetic resonance data suggest that mutation
      of Pro-35 causes a conformational change in the hydrophobic core of the molecule,
      whose integrity is required for the encapsidation of Vpr, and thus, Pro-35
      supports the replication of R5-tropic HIV-1 in HLT.

PMID- 17553869
TI  - Cathepsin B mediates cleavage of herpes simplex virus type 1 origin binding
      protein (OBP) to yield OBPC-1, and cleavage is dependent upon viral DNA
      replication.
AB  - Although the seven viral proteins required for herpes simplex virus type 1 (HSV
      1) DNA replication have been identified, the mechanism by which viral DNA
      synthesis is regulated is unclear. HSV-1 DNA replication is thought to occur in
      two stages: origin-dependent DNA replication (stage I) mediated by the origin
      binding protein (OBP), followed by origin- and OBP-independent DNA replication
      (stage II). The mechanism that facilitates the switch from stage I to stage II is
      unknown; however, it must involve the loss of OBP function or OBP itself from the
      replication initiation complex. Previous studies from this laboratory identified
      a transcript (UL8.5) and protein (OBPC) that are in frame with and comprise the C
      terminus of the gene specifying OBP. Because of its DNA binding ability, OBPC has
      been hypothesized to mediate the switch from stage I to stage II. Here, we
      identify a second protein (OBPC-2) that is also in frame with the C terminus of
      OBP but comprises a smaller portion of the protein. We demonstrate that the
      protein originally identified (OBPC-1) is a cathepsin B-mediated cleavage product
      of OBP, while OBPC-2 may be the product of the UL8.5 transcript. We further
      demonstrate that the cleavage of OBP to yield OBPC-1 is dependent upon viral DNA
      replication. These results suggest that cleavage may be a mechanism by which OBP
      levels and/or activity are regulated during infection.

PMID- 17553870
TI  - Hepatitis B virus maturation is sensitive to functional inhibition of ESCRT-III,
      Vps4, and gamma 2-adaptin.
AB  - Hepatitis B virus (HBV) is an enveloped DNA virus that presumably buds at
      intracellular membranes of infected cells. HBV budding involves two endocytic
      host proteins, the ubiquitin-interacting adaptor gamma 2-adaptin and the Nedd4
      ubiquitin ligase. Here, we demonstrate that HBV release also requires the
      cellular machinery that generates internal vesicles of multivesicular bodies
      (MVBs). In order to perturb the MVB machinery in HBV-replicating liver cells, we
      used ectopic expression of dominant-negative mutants of different MVB components,
      like the ESCRT-III complex-forming CHMP proteins and the Vps4 ATPases. Upon
      coexpression of mutated CHMP3, CHMP4B, or CHMP4C forms, as well as of ATPase
      defective Vps4A or Vps4B mutants, HBV assembly and egress were potently blocked.
      Each of the MVB inhibitors arrested virus particle maturation by entrapping the
      viral core and large and small envelope proteins in detergent-insoluble membrane
      structures that closely resembled aberrant endosomal class E compartments. In
      contrast, HBV subvirus particle release was not affected by MVB inhibitors,
      hinting at different export routes used by viral and subviral particles. To
      further define the role gamma 2-adaptin plays in HBV formation, we examined the
      effects of its overexpression in virus-replicating cells. Intriguingly, excess
      gamma 2-adaptin blocked HBV production in a manner similar to the actions of CHMP
      and Vps4 mutants. Moreover, overexpressed gamma 2-adaptin perturbed the endosomal
      morphology and diminished the budding of a retroviral Gag protein, implying that
      it may act as a principal inhibitor of the MVB sorting pathway. Together, these
      results demonstrate that HBV exploits the MVB machinery with the aid of gamma 2
      adaptin.

PMID- 17553871
TI  - Vpr cytopathicity independent of G2/M cell cycle arrest in human immunodeficiency
      virus type 1-infected CD4+ T cells.
AB  - The mechanism of CD4(+) T-cell depletion in human immunodeficiency virus type 1
      (HIV-1)-infected individuals remains unknown, although mounting evidence suggests
      that direct viral cytopathicity contributes to this loss. The HIV-1 Vpr accessory
      protein causes cell death and arrests cells in the G(2)/M phase; however, the
      molecular mechanism underlying these properties is not clear. Mutation of
      hydrophobic residues on the surface of its third alpha-helix disrupted Vpr
      toxicity, G(2)/M arrest induction, nuclear localization, and self-association,
      implicating this region in multiple Vpr functions. Cytopathicity by virion
      delivered mutant Vpr protein correlated with G(2)/M arrest induction but not
      nuclear localization or self-association. However, infection with whole virus
      encoding these Vpr mutants did not abrogate HIV-1-induced cell killing. Rather,
      mutant Vpr proteins that are impaired for G(2)/M block still prevented infected
      cell proliferation, and this property correlated with the death of infected
      cells. Chemical agents that inhibit infected cells from entering G(2)/M also did
      not reduce HIV-1 cytopathicity. Combined, these data implicate Vpr in HIV-1
      killing through a mechanism involving inhibiting cell division but not
      necessarily in G(2)/M. Thus, the hydrophobic region of the third alpha-helix of
      Vpr is crucial for mediating G(2)/M arrest, nuclear localization, and self
      association but dispensable for HIV-1 cytopathicity due to residual cell
      proliferation blockade mediated by a separate region of the protein.

PMID- 17553873
TI  - Molecular changes in the polymerase genes (PA and PB1) associated with high
      pathogenicity of H5N1 influenza virus in mallard ducks.
AB  - The highly pathogenic (HP) influenza viruses H5 and H7 are usually nonpathogenic
      in mallard ducks. However, the currently circulating HP H5N1 viruses acquired a
      different phenotype and are able to cause mortality in mallards. To establish the
      molecular basis of this phenotype, we cloned the human A/Vietnam/1203/04 (H5N1)
      influenza virus isolate that is highly pathogenic in ferrets, mice, and mallards
      and found it to be a heterogeneous mixture. Large-plaque isolates were highly
      pathogenic to ducks, mice, and ferrets, whereas small-plaque isolates were
      nonpathogenic in these species. Sequence analysis of the entire genome revealed
      that the small-plaque and the large-plaque isolates differed in the coding of
      five amino acids. There were two differences in the hemagglutinin (HA) gene (K52T
      and A544V), one in the PA gene (T515A), and two in the PB1 gene (K207R and
      Y436H). We inserted the amino acid changes into the wild-type reverse genetic
      virus construct to assess their effects on pathogenicity in vivo. The HA gene
      mutations and the PB1 gene K207R mutation did not alter the HP phenotype of the
      large-plaque virus, whereas constructs with the PA (T515A) and PB1 (Y436H) gene
      mutations were nonpathogenic in orally inoculated ducks. The PB1 (Y436H)
      construct was not efficiently transmitted in ducks, whereas the PA (T515A)
      construct replicated as well as the wild-type virus did and was transmitted
      efficiently. These results show that the PA and PB1 genes of HP H5N1 influenza
      viruses are associated with lethality in ducks. The mechanisms of lethality and
      the perpetuation of this lethal phenotype in ducks in nature remain to be
      determined.

PMID- 17553872
TI  - Cyclosporine inhibits mouse cytomegalovirus infection via a cyclophilin-dependent
      pathway specifically in neural stem/progenitor cells.
AB  - The potential of neural stem and progenitor cell (NSPC) transplantation in
      neurodegenerative disease raises a concern about immunosuppressive agents and
      opportunistic neurotropic pathogens that may interfere with engraftment.
      Cytomegalovirus (CMV) is an important opportunistic pathogen infecting the
      central nervous system, where it may remain latent for life, following
      transplacental transmission. Cyclosporine (Cs), an immunosuppressive drug used in
      organ transplantation, where its use is associated with CMV reactivation,
      suppressed murine CMV (MCMV) infection in cultured NSPCs but not in fibroblasts.
      This activity of Cs appears to be mediated via cyclophilin (CyP) rather than via
      calcineurin. First, the calcineurin-specific inhibitor FK506 failed to suppress
      replication. Second, the CyP-specific inhibitor NIM811 strongly suppressed
      replication in NSPC. NSPCs maintained in the presence of NIM811 retained viral
      genomes for several weeks without detectable viral gene expression or obvious
      deleterious effects. The withdrawal of NIM811 reactivated viral replication,
      suggesting that the inhibitory mechanism was reversible. Finally, inhibition of
      endogenous CyP A (CyPA) by small interfering RNA also inhibited replication in
      NSPCs. These results show that MCMV replication depends upon cellular CyPA
      pathways in NSPCs (in a specific cell type-dependent fashion), that CyPA plays an
      important role in viral infection in this cell type, and that inhibition of viral
      replication via CyP leads to persistence of the viral genome without cell damage.
      Further, the calcineurin-signaling pathway conferring immunosuppression in T
      cells does not influence viral replication in a detectable fashion.

PMID- 17553874
TI  - Tissue-specific and inducer-specific differential induction of ISG56 and ISG54 in
      mice.
AB  - The interferon-stimulated genes (ISGs) ISG56 and ISG54 are strongly induced in
      cultured cells by type I interferons (IFNs), viruses, and double-stranded RNA
      (dsRNA), which activate their transcription by various signaling pathways. Here
      we studied the stimulus-dependent induction of both genes in vivo. dsRNA, which
      is generated during virus infection, induced the expression of both genes in all
      organs examined. Induction was not seen in STAT1-deficient mice, indicating that
      dsRNA-induced gene expression requires endogenous IFN. We further examined the
      regulation of these ISGs in several organs from mice injected with dsRNA or IFN
      beta. Both ISG56 and ISG54 were widely expressed and at comparable levels.
      However, in organs isolated from mice injected with IFN-alpha the expression of
      ISG54 was reduced and more restricted in distribution compared with the
      expression level and distribution of ISG56. When we began to study specific cell
      types, splenic B cells showed ISG54 but not ISG56 expression in response to all
      agonists. Finally, in livers isolated from mice infected with vesicular
      stomatitis virus, the expression of ISG56, but not ISG54, was induced; this
      difference was observed at both protein and mRNA levels. These studies have
      revealed unexpected complexity in IFN-stimulated gene induction in vivo. For the
      first time we showed that the two closely related genes are expressed in a tissue
      specific and inducer-specific manner. Furthermore, our findings provide the first
      evidence of a differential pattern of expression of ISG54 and ISG56 genes by IFN
      alpha and IFN-beta.

PMID- 17553875
TI  - Processing of capsid protein by cathepsin L plays a crucial role in replication
      of Japanese encephalitis virus in neural and macrophage cells.
AB  - The flavivirus capsid protein not only is a component of nucleocapsids but also
      plays a role in viral replication. In this study, we found a small capsid protein
      in cells infected with Japanese encephalitis virus (JEV) but not in the viral
      particles. The small capsid protein was shown to be generated by processing with
      host cysteine protease cathepsin L. An in vitro cleavage assay revealed that
      cathepsin L cleaves the capsid protein between amino acid residues Lys(18) and
      Arg(19), which are well conserved among the mosquito-borne flaviviruses. A mutant
      JEV resistant to the cleavage of the capsid protein by cathepsin L was generated
      from an infectious cDNA clone of JEV by introducing a substitution in the
      cleavage site. The mutant JEV exhibited growth kinetics similar to those of the
      wild-type JEV in monkey (Vero), mosquito (C6/36), and porcine (PK15) cell lines,
      whereas replication of the mutant JEV in mouse macrophage (RAW264.7) and
      neuroblastoma (N18) cells was impaired. Furthermore, the neurovirulence and
      neuroinvasiveness of the mutant JEV to mice were lower than those of the wild
      type JEV. These results suggest that the processing of the JEV capsid protein by
      cathepsin L plays a crucial role in the replication of JEV in neural and
      macrophage cells, which leads to the pathogenesis of JEV infection.

PMID- 17553876
TI  - The amino terminus of varicella-zoster virus (VZV) glycoprotein E is required for
      binding to insulin-degrading enzyme, a VZV receptor.
AB  - Varicella-zoster virus (VZV) glycoprotein E (gE) is required for VZV infection.
      Although gE is well conserved among alphaherpesviruses, the amino terminus of VZV
      gE is unique. Previously, we showed that gE interacts with insulin-degrading
      enzyme (IDE) and facilitates VZV infection and cell-to-cell spread of the virus.
      Here we define the region of VZV gE required to bind IDE. Deletion of amino acids
      32 to 71 of gE, located immediately after the predicted signal peptide, resulted
      in loss of the ability of gE to bind IDE. A synthetic peptide corresponding to
      amino acids 24 to 50 of gE blocked its interaction with IDE in a concentration
      dependent manner. However, a chimeric gE in which amino acids 1 to 71 of VZV gE
      were fused to amino acids 30 to 545 of herpes simplex virus type 2 gE did not
      show an increased level of binding to IDE compared with that of full-length HSV
      gE. Thus, amino acids 24 to 71 of gE are required for IDE binding, and the
      secondary structure of gE is critical for the interaction. VZV gE also forms a
      heterodimer with glycoprotein gI. Deletion of amino acids 163 to 208 of gE
      severely reduced its ability to form a complex with gI. The amino portion of IDE,
      as well an IDE mutant in the catalytic domain of the protein, bound to gE.
      Therefore, distinct motifs of VZV gE are important for binding to IDE or to gI.

PMID- 17553877
TI  - Hydrophobic residues that form putative fusion loops of Epstein-Barr virus
      glycoprotein B are critical for fusion activity.
AB  - To test the importance of the hydrophobic residues within the putative Epstein
      Barr virus (EBV) glycoprotein B (gB) fusion loops in membrane fusion, WY(112-113)
      and WLIW(193-196) were mutated into alanine, glutamic acid, or the analogous
      residues from herpes simplex virus type 1 (HSV-1) gB (HR and RVEA). All gB
      variants exhibited cell surface expression, demonstrating that the substitutions
      did not perturb gB trafficking. None of six gB variants was, however, capable of
      mediating fusion with either epithelial or B cells. These data demonstrate that
      the bulky and hydrophobic EBV loop residues, which differ from the more
      hydrophilic HSV-1 residues and appear more compatible with membrane insertion,
      are essential for EBV gB-dependent fusion.

PMID- 17553878
TI  - Evolutionary processes among sylvatic dengue type 2 viruses.
AB  - Sylvatic dengue viruses (DENV) are transmitted in an enzootic cycle between
      nonhuman primates and arboreal Aedes mosquitoes in Southeast Asia and West
      Africa. Although previous analyses have revealed the evolutionary processes among
      endemic (human) DENV, little is known about viral evolution in the sylvatic
      cycle. Through an analysis of 14 complete coding regions of sylvatic Dengue type
      2 virus sampled over a 33-year period, we show that both the rate of evolutionary
      change and the pattern of natural selection are similar among endemic and
      sylvatic DENV, although the latter have a uniquely high frequency of positive
      selection in the NS4B protein gene. Our findings support a recent cross-species
      transmission event and suggest the possibility of future DENV reemergence from
      the sylvatic cycle.

PMID- 17553879
TI  - Efficient in vitro amplification of chronic wasting disease PrPRES.
AB  - Chronic wasting disease (CWD) of cervids is associated with conversion of the
      normal cervid prion protein, PrP(C), to a protease-resistant conformer, PrP(CWD).
      Here we report the use of both nondenaturing amplification and protein-misfolding
      cyclic amplification (PMCA) to amplify PrP(CWD) in vitro. Normal brains from
      deer, transgenic mice expressing cervid PrP(C) [Tg(cerPrP)1536 mice], and ferrets
      supported amplification. PMCA using normal Tg(cerPrP)1536 brains as the PrP(C)
      substrate produced >6.5 x 10(9)-fold amplification after six rounds. Highly
      efficient in vitro amplification of PrP(CWD) is a significant step toward
      detection of PrP(CWD) in the body fluids or excreta of CWD-susceptible species.

PMID- 17553880
TI  - Replication-competent recombinant vesicular stomatitis virus encoding hepatitis C
      virus envelope proteins.
AB  - Although in vitro replication of the hepatitis C virus (HCV) JFH1 clone of
      genotype 2a (HCVcc) has been developed, a robust cell culture system for the 1a
      and 1b genotypes, which are the most prevalent viruses in the world and resistant
      to interferon therapy, has not yet been established. As a surrogate virus system,
      pseudotype viruses transiently bearing HCV envelope proteins based on the
      vesicular stomatitis virus (VSV) and retrovirus have been developed. Here, we
      have developed a replication-competent recombinant VSV with a genome encoding
      unmodified HCV E1 and E2 proteins in place of the VSV envelope protein (HCVrv) in
      human cell lines. HCVrv and a pseudotype VSV bearing the unmodified HCV envelope
      proteins (HCVpv) generated in 293T or Huh7 cells exhibited high infectivity in
      Huh7 cells. Generation of infectious HCVrv was limited in some cell lines
      examined. Furthermore, HCVrv but not HCVpv was able to propagate and form foci in
      Huh7 cells. The infection of Huh7 cells with HCVpv and HCVrv was neutralized by
      anti-hCD81 and anti-E2 antibodies and by sera from chronic HCV patients. The
      infectivity of HCVrv was inhibited by an endoplasmic reticulum alpha-glucosidase
      inhibitor, N-(n-nonyl) deoxynojirimycin (Nn-DNJ), but not by a Golgi mannosidase
      inhibitor, deoxymannojirimycin. Focus formation of HCVrv in Huh7 cells was
      impaired by Nn-DNJ treatment. These results indicate that the HCVrv developed in
      this study can be used to study HCV envelope proteins with respect to not only
      the biological functions in the entry process but also their maturation step.

PMID- 17553881
TI  - Neutralization of human papillomavirus with monoclonal antibodies reveals
      different mechanisms of inhibition.
AB  - The mechanisms of human papillomavirus (HPV) neutralization by antibodies are
      incompletely understood. We have used HPV16 pseudovirus infection of HaCaT cells
      to analyze how several neutralizing monoclonal antibodies (MAbs) generated
      against HPV16 L1 interfere with the process of keratinocyte infection. HPV16
      capsids normally bind to both the cell surface and extracellular matrix (ECM) of
      HaCaT cells. Surprisingly, two strongly neutralizing MAbs, V5 and E70, did not
      prevent attachment of capsids to the cell surface. However, they did block
      association with the ECM and prevented internalization of cell surface-bound
      capsids. In contrast, MAb U4 prevented binding to the cell surface but not to the
      ECM. The epitope recognized by U4 was inaccessible when virions were bound to the
      cell surface but became accessible after endocytosis, presumably coinciding with
      receptor detachment. Treatment of capsids with heparin, which is known to
      interfere with binding to cell surface heparan sulfate proteoglycans (HSPGs),
      also resulted in HPV16 localization to the ECM. These results suggest that the U4
      epitope on the intercapsomeric C-terminal arm is likely to encompass the critical
      HSPG interaction residues for HPV16, while the V5 and E70 epitopes at the apex of
      the capsomer overlap the ECM-binding sites. We conclude that neutralizing
      antibodies can inhibit HPV infection by multiple distinct mechanisms, and
      understanding these mechanisms can add insight to the HPV entry processes.

PMID- 17553882
TI  - Targeting of adenovirus serotype 5 (Ad5) and 5/47 pseudotyped vectors in vivo:
      fundamental involvement of coagulation factors and redundancy of CAR binding by
      Ad5.
AB  - Vitamin K-dependent coagulation factors can promote adenoviral cell transduction
      in vitro. In vivo, warfarin pretreatment ablates liver targeting of an adenovirus
      serotype 5 (Ad5) vector deleted of CAR binding capability. Here, we assess in
      vivo transduction and biodistribution of Ad5 vectors with nonmodified fibers
      (Ad5) and a serotype 47 fiber-pseudotyped Ad5 (Ad5/47; subgroup D) virus
      following intravascular injection. Warfarin reduced liver transduction by both
      viruses. However, no impact on early liver virus accumulation was observed,
      suggesting no effect on Kupffer cell interactions. Hence, coagulation factors
      play a pivotal role in selectively mediating liver hepatocyte transduction of Ad5
      and Ad5/47 vectors.

PMID- 17553884
TI  - Two distinct low-pH steps promote entry of vaccinia virus.
AB  - Entry of vaccinia virus into cells occurs by an endosomal route as well as
      through the plasma membrane. Evidence for an endosomal pathway was based on
      findings that treatment at a pH of <6 of mature virions attached to the plasma
      membrane enhances entry, whereas inhibitors of endosomal acidification reduce
      entry. Inactivation of infectivity by low-pH treatment of virions prior to
      membrane attachment is characteristic of many viruses that use the endosomal
      route. Nevertheless, we show here that the exposure of unattached vaccinia virus
      virions to low pH at 37 degrees C did not alter their infectivity. Instead, such
      treatment stably activated virions as indicated by their accelerated entry upon
      subsequent addition to cells, as measured by reporter gene expression. Moreover,
      the rate of entry was not further enhanced by a second low-pH treatment following
      adsorption to the plasma membrane. However, the entry of virions activated prior
      to adsorption remained sensitive to inhibitors of endosomal acidification,
      whereas virions treated with low pH after adsorption were resistant. Activation
      of virions by low pH was closely mimicked by proteinase digestion, suggesting
      that the two treatments operate through a related mechanism. Although proteinase
      cleavage of the virion surface proteins D8 and A27 correlated with activation,
      mutant viruses constructed by individually deleting these genes did not exhibit
      an activated phenotype. We propose a two-step model of vaccinia virus entry
      through endosomes, in which activating or unmasking the fusion complex by low pH
      or by proteinase is rate limiting but does not eliminate a second low-pH step
      mediating membrane fusion.

PMID- 17553883
TI  - A protein kinase A-dependent mechanism by which rotavirus affects the
      distribution and mRNA level of the functional tight junction-associated protein,
      occludin, in human differentiated intestinal Caco-2 cells.
AB  - We found that at the tight junctions (TJs) of Caco-2 cell monolayers, rhesus
      monkey rotavirus (RRV) infection induced the disappearance of occludin. Confocal
      laser scanning microscopy showed the disappearance of occludin from the cell-cell
      boundaries without modifying the expression of the other TJ-associated proteins,
      ZO-1 and ZO-3. Western immunoblot analysis of RRV-infected cells showed a
      significant fall in the levels of the nonphosphorylated form of occludin in both
      Triton X-100-insoluble and Triton X-100-soluble fractions, without any change in
      the levels of the phosphorylated form of occludin. Quantitative reverse
      transcription-PCRs revealed that the level of transcription of the gene that
      encodes occludin was significantly reduced in RRV-infected cells. Treatment of
      RRV-infected cells with Rp-cyclic AMP and protein kinase A inhibitors H89 and
      KT5720 during the time course of the infection restored the distribution of
      occludin and a normal level of transcription of the gene that encodes occludin.

PMID- 17553885
TI  - Multiple-cytokine-producing antiviral CD4 T cells are functionally superior to
      single-cytokine-producing cells.
AB  - Virus-specific CD4 T cells are endowed with multiple functions, such as cytokine
      production, CD40 ligand (CD40L) expression (associated with the costimulation of
      CD8 and B cells), and degranulation (associated with cytotoxic potential). Here,
      we used antiviral CD4 T cells present in human blood to evaluate the relationship
      between cytokine production and other functions of CD4 T cells. Antiviral CD4 T
      cells specific for a virus causing persistent infection, cytomegalovirus (CMV),
      and two viruses causing nonpersistent infections, influenza virus and the
      smallpox vaccine virus (vaccinia virus), were studied. CD4 T cells specific for
      each of the viruses produced all seven possible combinations of the cytokines
      gamma interferon (IFN-gamma), interleukin-2, and tumor necrosis factor alpha.
      Cells producing three or two cytokines (triple producers and double producers)
      represented nearly 50% of the total response to each of the viruses. Triple
      producers expressed the highest levels of cytokines per cell, and single
      producers expressed the lowest. Following stimulation, higher frequencies of
      triple producers than single producers expressed CD40L. Only CMV-specific CD4 T
      cells underwent degranulation. However, higher frequencies of CMV-specific triple
      producers than single producers showed this functional characteristic. In
      contrast to the functional phenotypes, the memory phenotypes of triple producers
      and IFN-gamma single producers did not differ. These results demonstrate a strong
      positive association between the cytokine coproduction capacity of a virus
      specific CD4 T cell and its other functional characteristics and suggest that
      vaccines should aim to elicit T cells that coproduce more than one cytokine.

PMID- 17553886
TI  - Recombination confounds the early evolutionary history of human immunodeficiency
      virus type 1: subtype G is a circulating recombinant form.
AB  - Human immunodeficiency virus type 1 (HIV-1) is classified in nine subtypes (A to
      D, F, G, H, J, and K), a number of subsubtypes, and several circulating
      recombinant forms (CRFs). Due to the high level of genetic diversity within HIV-1
      and to its worldwide distribution, this classification system is widely used in
      fields as diverse as vaccine development, evolution, epidemiology, viral fitness,
      and drug resistance. Here, we demonstrate how the high recombination rates of HIV
      1 may confound the study of its evolutionary history and classification. Our data
      show that subtype G, currently classified as a pure subtype, has in fact a
      recombinant history, having evolved following recombination between subtypes A
      and J and a putative subtype G parent. In addition, we find no evidence for
      recombination within one of the lineages currently classified as a CRF, CRF02_AG.
      Our analysis indicates that CRF02_AG was the parent of the recombinant subtype G,
      rather than the two having the opposite evolutionary relationship, as is
      currently proposed. Our results imply that the current classification of HIV-1
      subtypes and CRFs is an artifact of sampling history, rather than reflecting the
      evolutionary history of the virus. We suggest a reanalysis of all pure subtypes
      and CRFs in order to better understand how high rates of recombination have
      influenced HIV-1 evolutionary history.

PMID- 17553887
TI  - Caveolar endocytosis is critical for BK virus infection of human renal proximal
      tubular epithelial cells.
AB  - In recent years, BK virus (BKV) nephritis after renal transplantation has become
      a severe problem. The exact mechanisms of BKV cell entry and subsequent
      intracellular trafficking remain unknown. Since human renal proximal tubular
      epithelial cells (HRPTEC) represent a main natural target of BKV nephritis,
      analysis of BKV infection of HRPTEC is necessary to obtain additional insights
      into BKV biology and to develop novel strategies for the treatment of BKV
      nephritis. We coincubated HRPTEC with BKV and the cholesterol-depleting agents
      methyl beta cyclodextrin (MBCD) and nystatin (Nys), drugs inhibiting caveolar
      endocytosis. The percentage of infected cells (detected by immunofluorescence)
      and the cellular levels of BKV large T antigen expression (detected by Western
      blot analysis) were significantly decreased in both MBCD- and Nys-treated HPRTEC
      compared to the level in HRPTEC incubated with BKV alone. HRPTEC infection by BKV
      was also tested after small interfering RNA (siRNA)-dependent depletion of either
      the caveolar structural protein caveolin-1 (Cav-1) or clathrin, the major
      structural protein of clathrin-coated pits. BKV infection was inhibited in HRPTEC
      transfected with Cav-1 siRNA but not in HRPTEC transfected with clathrin siRNA.
      The colocalization of labeled BKV particles with either Cav-1 or clathrin was
      investigated by using fluorescent microscopy and image cross-correlation
      spectroscopy. The rate of colocalization of BKV with Cav-1 peaked at 4 h after
      incubation. Colocalization with clathrin was insignificant at all time points.
      These results suggest that BKV entered into HRPTEC via caveolae, not clathrin
      coated pits, and that BKV is maximally associated with caveolae at 4 h after
      infection, prior to relocation to a different intracellular compartment.

PMID- 17553888
TI  - Environment determines fidelity for an RNA virus replicase.
AB  - The rate of insertion and deletion mutations of the replicase of Cucumber mosaic
      virus (CMV) was determined in planta by using a parasitic satellite RNA (satRNA)
      as a reporter. We found that the CMV replicase had different fidelity in
      different environments, with important implications in viral disease evolution.
      Insertions were very rare events, irrespective of the region of the satRNA genome
      assayed and independent of the hosts tested. On the other hand, deletion events
      were more frequent but were restricted to a highly structured region of the
      reporter. Deletion mutation rates were different for the two hosts tested,
      although the mutation distribution was not influenced by the hosts. Moreover, hot
      spots with high mutation rates were identified on the satRNA genome.

PMID- 17553889
TI  - Reversible inhibition of the fusion activity of measles virus F protein by an
      engineered intersubunit disulfide bridge.
AB  - In search of target sites for the development of paramyxovirus inhibitors, we
      have engineered disulfide bridges to introduce covalent links into the prefusion
      F protein trimer of measles virus. F-Edm-452C/460C, predicted to bridge head and
      stalk domains of different F monomers, shows a high degree of proteolytic
      maturation and surface expression, predominantly as stable, dithiothreitol
      sensitive trimers, but no fusion activity. Reduction of disulfide bridges
      partially restores activity. These findings underscore the importance of
      reversible intersubunit interactions between the stalk and head domains for F
      activity. Noncovalent small molecules mimicking this behavior may constitute a
      potent strategy for preventing paramyxovirus entry.

PMID- 17553890
TI  - Measles virus-specific CD4 T-cell activity does not correlate with protection
      against lung infection or viral clearance.
AB  - Acute measles in children can be prevented by immunization with the live
      attenuated measles vaccine virus. Although immunization is able to induce CD4 and
      CD8 T cells as well as neutralizing antibodies, only the latter have been
      correlated with protective immunity. CD8 T cells, however, have been documented
      to be important in viral clearance in the respiratory tract, whereas CD4 T cells
      have been shown to be protective in a mouse encephalitis model. In order to
      investigate the CD4 T-cell response in infection of the respiratory tract, we
      have defined a T-cell epitope in the hemagglutinin (H) protein for immunization
      and developed a monoclonal antibody for depletion of CD4 T cells in the cotton
      rat model. Although the kinetics of CD4 T-cell development correlated with
      clearance of virus, the depletion of CD4 T cells during the primary infection did
      not influence viral titers in lung tissue. Immunization with the H epitope
      induced a CD4 T-cell response but did not protect against infection. Immunization
      in the presence of maternal antibodies resulted in the development of a CD4 T
      cell response which (in the absence of neutralizing antibodies) did not protect
      against infection. In summary, CD4 T cells do not seem to protect against
      infection after immunization and do not participate in clearance of virus
      infection from lung tissue during measles virus infection. We speculate that the
      major role of CD4 T cells is to control and clear virus infection from other
      affected organs like the brain.

PMID- 17553892
TI  - Characterization and function of putative substrate specificity domain in
      microvirus external scaffolding proteins.
AB  - Microviruses (canonical members are bacteriophages phiX174, G4, and alpha3) are
      T=1 icosahedral virions with an assembly pathway mediated by two scaffolding
      proteins. The external scaffolding protein D plays a major role during
      morphogenesis, particularly in icosahedral shell formation. The results of
      previous studies, conducted with a cloned chimeric external scaffolding gene,
      suggest that the first alpha-helix acts as a substrate specificity domain,
      perhaps mediating the initial coat-external scaffolding protein interaction.
      However, the expression of a cloned gene could lead to protein concentrations
      higher than those found in typical infections. Moreover, its induction before
      infection could alter the timing of the protein's accumulation. Both of these
      factors could drive or facilitate reactions that may not occur under
      physiological conditions or before programmed cell lysis. In order to elucidate a
      more detailed mechanistic model, a chimeric external scaffolding gene was placed
      directly in the phiX174 genome under wild-type transcriptional and translational
      control, and the chimeric virus, which was not viable on the level of plaque
      formation, was characterized. The results of the genetic and biochemical analyses
      indicate that alpha-helix 1 most likely mediates the nucleation reaction for the
      formation of the first assembly intermediate containing the external scaffolding
      protein. Mutants that can more efficiently use the chimeric scaffolding protein
      were isolated. These second-site mutations appear to act on a kinetic level,
      shortening the lag phase before virion production, perhaps lowering the critical
      concentration of the chimeric protein required for a nucleation reaction.

PMID- 17553891
TI  - N-linked glycosylation attenuates H3N2 influenza viruses.
AB  - Over the last four decades, H3N2 subtype influenza A viruses have gradually
      acquired additional potential sites for glycosylation within the globular head of
      the hemagglutinin (HA) protein. Here, we have examined the biological effect of
      additional glycosylation on the virulence of H3N2 influenza viruses. We created
      otherwise isogenic reassortant viruses by site-directed mutagenesis that contain
      additional potential sites for glycosylation and examined the effect on virulence
      in naive BALB/c, C57BL/6, and surfactant protein D (SP-D)-deficient mice. The
      introduction of additional sites was consistent with the sequence of acquisition
      in the globular head over the past 40 years, beginning with two sites in 1968 to
      the seven sites found in contemporary influenza viruses circulating in 2000.
      Decreased morbidity and mortality, as well as lower viral lung titers, were seen
      in mice as the level of potential glycosylation of the viruses increased. This
      correlated with decreased evidence of virus-mediated lung damage and increased in
      vitro inhibition of hemagglutination by SP-D. SP-D-deficient animals displayed an
      inverse pattern of disease, such that more highly glycosylated viruses elicited
      disease equivalent to or exceeding that of the wild type. We conclude from these
      data that increased glycosylation of influenza viruses results in decreased
      virulence, which is at least partly mediated by SP-D-induced clearance from the
      lung. The continued exploration of interactions between highly glycosylated
      viruses and surfactant proteins may lead to an improved understanding of the
      biology within the lung and strategies for viral control.

PMID- 17553893
TI  - Borna disease virus infection impairs synaptic plasticity.
AB  - The mechanisms whereby Borna disease virus (BDV) can impair neuronal function and
      lead to neurobehavioral disease are not well understood. To analyze the
      electrophysiological properties of neurons infected with BDV, we used cultures of
      neurons grown on multielectrode arrays, allowing a real-time monitoring of the
      electrical activity across the network shaped by synaptic transmission. Although
      infection did not affect spontaneous neuronal activity, it selectively blocked
      activity-dependent enhancement of neuronal network activity, one form of synaptic
      plasticity thought to be important for learning and memory. These findings
      highlight the original mechanism of the neuronal dysfunction caused by
      noncytolytic infection with BDV.

PMID- 17553894
TI  - Decreased CXCR3+ CD8 T cells in advanced human immunodeficiency virus infection
      suggest that a homing defect contributes to cytotoxic T-lymphocyte dysfunction.
AB  - To exert their cytotoxic function, cytotoxic T-lymphocytes (CTL) must be
      recruited into infected lymphoid tissue where the majority of human
      immunodeficiency virus (HIV) replication occurs. Normally, effector T cells exit
      lymph nodes (LNs) and home to peripheral sites of infection. How HIV-specific CTL
      migrate into lymphoid tissue from which they are normally excluded is unknown. We
      investigated which chemokines and receptors mediate this reverse homing and
      whether impairment of this homing could contribute to CTL dysfunction as HIV
      infection progresses. Analysis of CTL chemokine receptor expression in the blood
      and LNs of untreated HIV-infected individuals with stable, chronic infection or
      advanced disease demonstrated that LNs were enriched for CXCR3(+) CD8 T cells in
      all subjects, suggesting a key role for this receptor in CTL homing to infected
      lymphoid tissue. Compared to subjects with chronic infection, however, subjects
      with advanced disease had fewer CXCR3(+) CD8 T cells in blood and LNs. CXCR3
      expression on bulk and HIV-specific CD8 T cells correlated positively with CD4
      count and negatively with viral load. In advanced infection, there was an
      accumulation of HIV-specific CD8 T cells at the effector memory stage; however,
      decreased numbers of CXCR3(+) CD8 T cells were seen across all maturation
      subsets. Plasma CXCL9 and CXCL10 were elevated in both infected groups in
      comparison to the levels in uninfected controls, whereas lower mRNA levels of
      CXCR3 ligands and CD8 in LNs were seen in advanced infection. These data suggest
      that both CXCR3(+) CD8 T cells and LN CXCR3 ligands decrease as HIV infection
      progresses, resulting in reduced homing of CTL into LNs and contributing to
      immune dysfunction.

PMID- 17553895
TI  - Semliki Forest virus nonstructural protein 2 is involved in suppression of the
      type I interferon response.
AB  - The type I interferons (IFNs) are potent mediators of antiviral immunity, and
      many viruses have developed means to block their expression or their effects.
      Semliki Forest virus (SFV) infection induces rapid and profound silencing of host
      cell gene expression, a process believed to be important for the inhibition of
      the IFN response. In SFV-infected cells, a large proportion of the nonstructural
      protein nsp2 is found in the nucleus, but a role for this localization has not
      been described. In this work we demonstrate that a viral mutant, SFV4-RDR, in
      which the nuclear localization sequence of nsp2 has been rendered inactive,
      induces a significantly more robust IFN response in infected cells. This mutant
      virus replicates at a rate similar to that of the parental SFV4 strain and also
      shuts off host cell gene expression to similar levels, indicating that the
      general cellular shutoff is not responsible for the inhibition of IFN expression.
      Further, the rate of virus-induced nuclear translocation of early IFN
      transcription factors was not found to differ between the wild-type and mutant
      viruses, indicating that the effect of nsp2 is at a later stage. These results
      provide novel information about the mode of action of this viral IFN antagonist.

PMID- 17553896
TI  - Phenotypic and functional changes of cytotoxic CD56pos natural T cells determine
      outcome of acute hepatitis C virus infection.
AB  - Innate CD56(pos) natural killer (NK) and natural T (NT) cells comprise important
      hepatic antiviral effector lymphocytes whose activity is fine-tuned through
      surface NK receptors (NKRs). Dysregulation of NKRs in patients with long-standing
      hepatitis C virus (HCV) infection has been shown, but little is known regarding
      NKRs in acute infection. Treatment-naive patients with acute HCV (n = 22),
      including 10 with spontaneous recovery, were prospectively studied. CD56(pos) NT
      levels were reduced early in acute HCV infection and did not fluctuate over time.
      In resolving HCV infection, NT cells with a more activated phenotype (lower
      CD158A and higher natural cytotoxicity receptor expression) at baseline predated
      spontaneous recovery. Moreover, NKG2A expression on CD56(+) NT cells correlated
      directly with circulating HCV RNA levels. Deficient interleukin-13 (IL-13)
      production by NT cells and reduced IL-2-activated killing (LAK) at baseline were
      associated with the ultimate development of persistence. These results indicate a
      previously unappreciated role for NT cells in acute HCV infection and identify a
      potential target for pharmacologic manipulation.

PMID- 17553897
TI  - Expression of the mu opioid receptor in the human immunodeficiency virus type 1
      transgenic rat model.
AB  - Opioids, via the mu opioid receptor (MOR), can exacerbate bacterial infections
      and the immunopathogenesis of human immunodeficiency virus type 1 (HIV-1)
      infection. Recently, an HIV-1 transgenic (HIV-1Tg) rat model containing
      circulating HIV-1 gp120 was created. Using real-time reverse transcription-PCR,
      we found that MOR mRNA levels were significantly higher in the peritoneal
      macrophages of the HIV-1Tg rat than those in control animals. Lipopolysaccharide,
      a bacterial endotoxin, induced secretion of the inflammatory cytokines tumor
      necrosis factor alpha (TNF-alpha), interleukin-beta (IL-beta), and IL-10 in the
      HIV-1Tg rat and further increased MOR expression. Ex vivo studies showed that MOR
      expression was up-regulated in the peritoneal macrophages of F344 control rats by
      exposure to serum from HIV-1Tg rats and that MOR up-regulation was abolished by
      addition of gp120 antibody to the serum. In human TPA-differentiated HL-60 cells,
      which are macrophage-like cells, LPS-induced MOR mRNA up-regulation was greater
      in gp120-pretreated cells than in vehicle-pretreated cells. Our data suggest that
      in individuals infected with HIV-1, the MOR is up-regulated, possibly by
      circulating HIV-1 proteins such as gp120, and HIV-1 proteins may play a
      significant role in modulating the response to bacterial infection in opioid
      using HIV-infected individuals. Furthermore, our results demonstrate that the new
      HIV-1Tg rat model can be a valuable tool with which to study MOR gene expression
      and its effects in the continuous presence of HIV viral proteins.

PMID- 17553898
TI  - Heterologous prime/boost immunization of rhesus monkeys by using diverse poxvirus
      vectors.
AB  - As the diversity of potential immunogens increases within certain classes of
      vectors, the possibility has arisen of employing heterologous prime/boost
      immunizations using diverse members of the same family of vectors. The present
      study was initiated to explore the use of divergent pox vectors in a prime/boost
      regimen to elicit high-frequency cellular immune responses to human
      immunodeficiency virus type 1 envelope and simian immunodeficiency virus gag in
      rhesus monkeys. We demonstrated that monkeys vaccinated with a recombinant
      modified vaccinia virus Ankara (rMVA) prime/recombinant fowlpox virus (rFPV)
      boost regimen and monkeys vaccinated with a recombinant vaccinia virus prime/rFPV
      boost regimen developed comparable cellular immune responses that were greater in
      magnitude than those elicited by a homologous prime/boost with rMVA.
      Nevertheless, comparable magnitude recall cellular immune responses were observed
      in monkeys vaccinated with heterologous and homologous recombinant poxvirus
      following challenge with the CXCR4-tropic SHIV-89.6P. Consistent with this
      finding, comparable levels of containment of viral replication and CD4(+) T
      lymphocyte preservation were seen in these groups of recombinant poxvirus
      vaccinated monkeys. This study supports further exploration of combining
      recombinant vectors of the same family in prime/boost immunization strategies to
      optimize vaccine-elicited cellular immune responses.

PMID- 17553900
TI  - Prostate cancer associated with p53 and Rb deficiency arises from the
      stem/progenitor cell-enriched proximal region of prostatic ducts.
AB  - Recently, we have shown that prostate epithelium-specific deficiency for p53 and
      Rb tumor suppressors leads to metastatic cancer, exhibiting features of both
      luminal and neuroendocrine differentiation. Using stage-by-stage evaluation of
      carcinogenesis in this model, we report that all malignant neoplasms arise from
      the proximal region of the prostatic ducts, the compartment highly enriched for
      prostatic stem/progenitor cells. In close similarity to reported properties of
      prostatic stem cells, the cells of the earliest neoplastic lesions express stem
      cell marker stem cell antigen 1 and are not sensitive to androgen withdrawal.
      Like a subset of normal cells located in the proximal region of prostatic ducts,
      the early neoplastic cells coexpress luminal epithelium markers cytokeratin 8,
      androgen receptor, and neuroendocrine markers synaptophysin and chromogranin A.
      Inactivation of p53 and Rb also takes place in the lineage-committed transit
      amplifying and/or differentiated cells of the distal region of the prostatic
      ducts. However, the resulting prostatic intraepithelial neoplasms never progress
      to carcinoma by the time of mouse death. Interestingly, in an ectopic
      transplantation assay, early mutant cells derived from either region of the
      prostatic ducts are capable of forming neoplasms within 3 months. These findings
      indicate that p53 and Rb are critically important for the regulation of the
      prostatic stem cell compartment, the transformation in which may lead to
      particularly aggressive cancers in the context of microenvironment.

PMID- 17553901
TI  - Hawaii cohort study of serum micronutrient concentrations and clearance of
      incident oncogenic human papillomavirus infection of the cervix.
AB  - The degree to which the resolution of human papillomavirus (HPV) infection
      parallels exposure to other factors, particularly those related to nutritional
      status, is a relatively unexplored area of research. We established a cohort of
      women for long-term follow-up to examine the association of serum retinol,
      carotenoid, and tocopherol concentrations with the clearance of incident cervical
      HPV infection. Interviews and biological specimens were obtained at baseline and
      at 4-month intervals. At each visit, a cervical cell specimen for HPV DNA
      analysis and cytology and a fasting blood sample to measure micronutrient levels
      were collected. A Cox proportional hazards model was used to study the
      relationship between clearance of 189 incident (type-specific) oncogenic HPV
      infections and the levels of 20 serum micronutrients among 122 women. Higher
      circulating levels of trans-zeaxanthin, total trans-lutein/zeaxanthin,
      cryptoxanthin (total and beta), total trans-lycopene and cis-lycopene, carotene
      (alpha, beta, and total), and total carotenoids were associated with a
      significant decrease in the clearance time of type-specific HPV infection,
      particularly during the early stages of infection (<or=120 days). HPV clearance
      time was also significantly shorter among women with the highest compared with
      the lowest serum levels of alpha-tocopherol and total-tocopherol, but significant
      trends in these associations were limited to infections lasting <or=120 days.
      Clearance of persistent HPV infection (lasting >120 days) was not significantly
      associated with circulating levels of carotenoids or tocopherols. Results from
      this investigation support an association of micronutrients with the rapid
      clearance of incident oncogenic HPV infection of the uterine cervix.

PMID- 17553899
TI  - A mutation in the human herpes simplex virus type 1 UL52 zinc finger motif
      results in defective primase activity but can recruit viral polymerase and
      support viral replication efficiently.
AB  - Herpes simplex virus type 1 (HSV-1) encodes a heterotrimeric helicase/primase
      complex consisting of UL5, UL8, and UL52. UL5 contains conserved helicase motifs,
      while UL52 contains conserved primase motifs, including a zinc finger motif.
      Although HSV-1 and HSV-2 UL52s contain a leucine residue at position 986, most
      other herpesvirus primase homologues contain a phenylalanine at this position. We
      constructed an HSV-1 UL52 L986F mutation and found that it can complement a UL52
      null virus more efficiently than the wild type (WT). We thus predicted that the
      UL5/8/52 complex containing the L986F mutation might possess increased primase
      activity; however, it exhibited only 25% of the WT level of primase activity.
      Interestingly, the mutant complex displayed elevated levels of DNA binding and
      single-stranded DNA-dependent ATPase and helicase activities. This result
      confirms a complex interdependence between the helicase and primase subunits. We
      previously showed that primase-defective mutants failed to recruit the polymerase
      catalytic subunit UL30 to prereplicative sites, suggesting that an active
      primase, or primer synthesis, is required for polymerase recruitment. Although
      L986F exhibits decreased primase activity, it can support efficient replication
      and recruit UL30 efficiently to replication compartments, indicating that a
      partially active primase is capable of recruiting polymerase. Extraction with
      detergents prior to fixation can extract nucleosolic proteins but not proteins
      bound to chromatin or the nuclear matrix. We showed that UL30 was extracted from
      replication compartments while UL42 remained bound, suggesting that UL30 may be
      tethered to the replication fork by protein-protein interactions.

PMID- 17553902
TI  - Oocyte-derived BMP15 and FGFs cooperate to promote glycolysis in cumulus cells.
AB  - Mammalian oocytes are deficient in their ability to carry out glycolysis.
      Therefore, the products of glycolysis that are necessary for oocyte development
      are provided to oocytes by companion cumulus cells. Mouse oocytes secrete
      paracrine factors that promote glycolysis in cumulus cells. The objective of this
      study was to identify paracrine factors secreted by oocytes that promote
      glycolysis and expression of mRNA encoding the glycolytic enzymes PFKP and LDHA.
      Candidates included growth differentiation factor 9 (GDF9), bone morphogenetic
      protein 15 (BMP15) and fibroblast growth factors (FGFs). Bmp15-/- and Gdf9+/-
      Bmp15-/- (double mutant, DM) cumulus cells exhibited reduced levels of both
      glycolysis and Pfkp and Ldha mRNA, and mutant oocytes were deficient in promoting
      glycolysis and expression of Pfkp and Ldha mRNA in cumulus cells of wild-type
      (WT) mice. Alone, neither recombinant BMP15, GDF9 nor FGF8 promoted glycolysis
      and expression of Pfkp and Ldha mRNA in WT cumulus cells. Co-treatment with BMP15
      and FGF8 promoted glycolysis and increased expression of Pfkp and Ldha mRNA in WT
      cumulus cells to the same levels as WT oocytes; however, the combinations of
      BMP15/GDF9 or GDF9/FGF8 did not. Furthermore, SU5402, an FGF receptor-dependent
      protein kinase inhibitor, inhibited Pfkp and Ldha expression in cumulus cells
      promoted by paracrine oocyte factors. Therefore, oocyte-derived BMP15 and FGFs
      cooperate to promote glycolysis in cumulus cells.

PMID- 17553903
TI  - AMP1 and MP antagonistically regulate embryo and meristem development in
      Arabidopsis.
AB  - AUXIN RESPONSE FACTOR (ARF)-mediated signaling conveys positional information
      during embryonic and postembryonic organogenesis and mutations in MONOPTEROS
      (MP/ARF5) result in severe patterning defects during embryonic and postembryonic
      development. Here we show that MP patterning activity is largely dispensable when
      the presumptive carboxypeptidase ALTERED MERISTEM PROGRAM 1 (AMP1) is not
      functional, indicating that MP is primarily necessary to counteract AMP1
      activity. Closer inspection of the single and double mutant phenotypes reveals
      antagonistic influences of both genes on meristematic activities throughout the
      Arabidopsis life cycle. In the absence of MP activity, cells in apical meristems
      and along the paths of procambium formation acquire differentiated identities and
      this is largely dependent on differentiation-promoting AMP1 activity. Positions
      of antagonistic interaction between MP and AMP1 coincide with MP expression
      domains within the larger AMP1 expression domain. These observations suggest a
      model in which auxin-derived positional information through MP carves out
      meristematic niches by locally overcoming a general differentiation-promoting
      activity involving AMP1.

PMID- 17553904
TI  - Ftm is a novel basal body protein of cilia involved in Shh signalling.
AB  - In this study we show in mice that Ftm (Rpgrip1l) is located at the ciliary basal
      body. Our data reveal that Ftm is necessary for developmental processes such as
      the establishment of left-right asymmetry and patterning of the neural tube and
      the limbs. The loss of Ftm affects the ratio of Gli3 activator to Gli3 repressor,
      suggesting an involvement of Ftm in Shh signalling. As Ftm is not essential for
      cilia assembly but for full Shh response, Ftm can be considered as a novel
      component for cilium-related Hh signalling. Furthermore, the absence of Ftm in
      arthropods underlines the divergence between vertebrate and Drosophila Hh
      pathways.

PMID- 17553905
TI  - What lies at the interface of regenerative medicine and developmental biology?
AB  - At a recent Keystone Symposium on 'Developmental Biology and Tissue Engineering',
      new findings in areas ranging from stem cell differentiation, embryonic pattern
      formation and organ regeneration to engineered cell microenvironments, synthetic
      biomaterials and artificial tissue fabrication were described. Although these new
      advances were exciting, this symposium clarified that biologists and engineers
      often view the challenge of tissue formation from different, and sometimes
      conflicting, perspectives. These dichotomies raise questions regarding the
      definition of regenerative medicine, but offer the promise of exciting new
      interdisciplinary approaches to tissue and organ regeneration, if effective
      alliances can be established.

PMID- 17553906
TI  - Involvement of vessels and PDGFB in muscle splitting during chick limb
      development.
AB  - Muscle formation and vascular assembly during embryonic development are usually
      considered separately. In this paper, we investigate the relationship between the
      vasculature and muscles during limb bud development. We show that endothelial
      cells are detected in limb regions before muscle cells and can organize
      themselves in space in the absence of muscles. In chick limbs, endothelial cells
      are detected in the future zones of muscle cleavage, delineating the cleavage
      pattern of muscle masses. We therefore perturbed vascular assembly in chick limbs
      by overexpressing VEGFA and demonstrated that ectopic blood vessels inhibit
      muscle formation, while promoting connective tissue. Conversely, local inhibition
      of vessel formation using a soluble form of VEGFR1 leads to muscle fusion. The
      endogenous location of endothelial cells in the future muscle cleavage zones and
      the inverse correlation between blood vessels and muscle suggests that vessels
      are involved in the muscle splitting process. We also identify the secreted
      factor PDGFB (expressed in endothelial cells) as a putative molecular candidate
      mediating the muscle-inhibiting and connective tissue-promoting functions of
      blood vessels. Finally, we propose that PDGFB promotes the production of
      extracellular matrix and attracts connective tissue cells to the future splitting
      site, allowing separation of the muscle masses during the splitting process.

PMID- 17553907
TI  - A Drosophila ortholog of the human cylindromatosis tumor suppressor gene
      regulates triglyceride content and antibacterial defense.
AB  - The cylindromatosis (CYLD) gene is mutated in human tumors of skin appendages. It
      encodes a deubiquitylating enzyme (CYLD) that is a negative regulator of the NF
      kappaB and JNK signaling pathways, in vitro. However, the tissue-specific
      function and regulation of CYLD in vivo are poorly understood. We established a
      genetically tractable animal model to initiate a systematic investigation of
      these issues by characterizing an ortholog of CYLD in Drosophila. Drosophila CYLD
      is broadly expressed during development and, in adult animals, is localized in
      the fat body, ovaries, testes, digestive tract and specific areas of the nervous
      system. We demonstrate that the protein product of Drosophila CYLD (CYLD), like
      its mammalian counterpart, is a deubiquitylating enzyme. Impairment of CYLD
      expression is associated with altered fat body morphology in adult flies,
      increased triglyceride levels and increased survival under starvation conditions.
      Furthermore, flies with compromised CYLD expression exhibited reduced resistance
      to bacterial infections. All mutant phenotypes described were reversible upon
      conditional expression of CYLD transgenes. Our results implicate CYLD in a broad
      range of functions associated with fat homeostasis and host defence in
      Drosophila.

PMID- 17553908
TI  - The rise and fall of Hox gene clusters.
AB  - Although all bilaterian animals have a related set of Hox genes, the genomic
      organization of this gene complement comes in different flavors. In some
      unrelated species, Hox genes are clustered; in others, they are not. This
      indicates that the bilaterian ancestor had a clustered Hox gene family and that,
      subsequently, this genomic organization was either maintained or lost.
      Remarkably, the tightest organization is found in vertebrates, raising the
      embarrassingly finalistic possibility that vertebrates have maintained best this
      ancestral configuration. Alternatively, could they have co-evolved with an
      increased ;organization' of the Hox clusters, possibly linked to their genomic
      amplification, which would be at odds with our current perception of evolutionary
      mechanisms? When discussing the why's and how's of Hox gene clustering, we need
      to account for three points: the mechanisms of cluster evolution; the underlying
      biological constraints; and the developmental modes of the animals under
      consideration. By integrating these parameters, general conclusions emerge that
      can help solve the aforementioned dilemma.

PMID- 17553909
TI  - The cost-effectiveness of etanercept in patients with severe ankylosing
      spondylitis in the UK.
AB  - OBJECTIVES: To examine the costs and benefits associated with long-term
      etanercept (ETN) treatment in patients with severe ankylosing spondylitis (AS) in
      the UK in accordance with the BSR guidelines. METHODS: A mathematical model was
      constructed to estimate the costs and benefits associated with ETN plus non
      steroidal anti-inflammatory drugs (NSAIDs) compared with NSAIDs alone. Individual
      patient data from Phase III RCTs was used to inform the proportion and magnitude
      of initial response to treatment and changes in health-related quality of life. A
      retrospective costing exercise on patients attending a UK secondary care
      rheumatology unit was used to inform disease costs. Published evidence on long
      term disease progression was extrapolated over a 25-yr horizon. Uncertainty was
      examined using probabilistic sensitivity analyses. RESULTS: Over a 25-yr horizon,
      ETN plus NSAIDs gave 1.58 more QALYs at an additional cost of 35,978 pounds when
      compared with NSAID treatment alone. This equates to a central estimate of 22,700
      pounds per QALY. The incremental cost per QALYs using shorter time periods were
      27,600 pounds, 23,600 pounds and 22,600 pounds at 2, 5 and 15 yrs, respectively.
      Using a 25-yr horizon, 93% of results from the probabilistic analyses fall below
      a threshold of 25,000 pounds per QALY. CONCLUSIONS: This study demonstrates the
      potential cost-effectiveness of ETN plus NSAIDs compared with NSAIDs alone in
      patients with severe AS treated according to the BSR guidelines in the UK.

PMID- 17553910
TI  - Prevalence of Wegener's granulomatosis, microscopic polyangiitis, polyarteritis
      nodosa and Churg-Strauss syndrome within a defined population in southern Sweden.
AB  - OBJECTIVES: To estimate the point prevalence (p.p.) of Wegener's granulomatosis
      (WG), microscopic polyangiitis (MPA), polyarteritis nodosa (PAN) and Churg
      Strauss syndrome (CSS) within a defined population in southern Sweden. METHOD: A
      cross-sectional p.p. study using multiple sources for case identification. The
      study area, a healthcare district around the city of Lund in southern Sweden
      (Mellersta Skanes sjukvardsdistrikt), had, on 31 December 2002, a total
      population of 287 479 inhabitants. All the identified cases were verified by
      medical record review. The patients were classified according to an algorithm
      based on the American College of Rheumatology classification criteria 1990 and
      the Chapel Hill Consensus Conference definitions 1994. RESULTS: Eighty-six
      patients (49% female) with a median age of 64.8 yrs (range 15-90.5) fulfilled the
      study criteria. There were 46 patients with WG; 27 with MPA; nine with PAN; and
      four with CSS. The p.p. per million inhabitants was estimated on 1 January 2003
      to be 160 (95% confidence interval 114-206) for WG, 94 (58-129) for MPA, 31 (11
      52) for PAN and 14 (0.3-27) for CSS. Capture-recapture analysis estimated the
      completeness of the case finding to 96%. CONCLUSIONS: The prevalence of WG, MPA,
      PAN and CSS in our district is the highest figure reported so far. Explanations
      for this finding may include high incidence, extensive ANCA-testing, good
      survival as well as sensitive search methods for case identification.

PMID- 17553912
TI  - Adalimumab-associated pulmonary fibrosis reply.

PMID- 17553913
TI  - Inhibition of human thiopurine S-methyltransferase by various nonsteroidal anti
      inflammatory drugs in vitro: a mechanism for possible drug interactions.
AB  - Thiopurine S-methyltransferase (TPMT) is a biotransformation phase II enzyme
      responsible for the metabolic inactivation of thiopurine drugs. The present study
      was carried out to investigate the inhibitory potential of 15 nonsteroidal anti
      inflammatory drugs (NSAIDs) on human TPMT activity in vitro. TPMT activity was
      measured in pooled human erythrocytes in the absence and presence of various
      NSAIDs using the previously published high-performance liquid chromatography-UV
      method. To determine the inhibition type and K(i) value for each compound, we
      performed kinetic analysis at five different inhibitor concentrations close to
      the IC(50) value obtained in preliminary experiments. Naproxen (K(i) = 52
      microM), mefenamic acid (K(i) = 39 microM), and tolfenamic acid (K(i) = 50
      microM) inhibited TPMT activity in a noncompetitive manner. The estimated K(i)
      values for the inhibition of TPMT by ketoprofen (K(i) = 172 microM) and ibuprofen
      (K(i) = 1043 microM) indicated that the propionic acid derivatives were
      relatively weak inhibitors of TPMT. Our results suggest that coadministration of
      thiopurines and various NSAIDs may lead to drug interactions.

PMID- 17553914
TI  - Effect of pregnane X receptor ligand on pharmacokinetics of substrates of organic
      cation transporter Oct1 in rats.
AB  - Because rat organic cation transporter 1 (Oct1, SLC22a1) is expressed mainly in
      the liver and mediates drug transport, its activity may determine the hepatic
      handling of cationic drugs. Here, we studied the regulation mechanism of the
      expression of Oct1, focusing on the nuclear receptors. In vitro studies using
      cultured hepatocytes indicated that expression of Oct1 was up-regulated by
      treatment with pregnenolone-16 alpha-carbonitrile (PCN) and by overexpression of
      rat pregnane X receptor (PXR). In addition, isolated rat hepatocytes exhibited an
      increase of 1-methyl-4-phenylpyridinium (MPP(+)) uptake on treatment with PCN.
      When rats were subcutaneously administered PCN, an increase of biliary excretion
      clearance and distribution volume was observed for drugs such as MPP(+),
      metformin, and tetraethylammonium, although the effects on pharmacokinetic
      parameters were variable among the tested drugs. In addition, the expression of
      Oct2 in kidney was increased by treatment with PCN. Thus, PXR ligands appear to
      regulate the expression of organic cation transporters in rats and thereby to
      influence the pharmacokinetic properties of cationic drugs. Because PXR ligands
      include various clinically used drugs, alterations of hepatic drug handling may
      arise from interactions between cationic drugs that are substrates of Oct1 and
      ligands of PXR.

PMID- 17553915
TI  - Kinetic studies of 25-hydroxy-19-nor-vitamin D3 and 1 alpha,25-dihydroxy-19-nor
      vitamin D3 hydroxylation by CYP27B1 and CYP24A1.
AB  - Our previous study demonstrated that 25-hydroxy-19-nor-vitamin D(3) [25(OH)-19
      nor-D(3)] inhibited the proliferation of immortalized noncancerous PZ-HPV-7
      prostate cells similar to 1 alpha,25-dihydroxyvitamin D(3) [1
      alpha,25(OH)(2)D(3)], suggesting that 25(OH)-19-nor-D(3) might be converted to 1
      alpha,25-dihydroxy-19-nor-vitamin D(3) [1 alpha,25(OH)(2)-19-nor-D(3)] by CYP27B1
      before exerting its antiproliferative activity. Using an in vitro cell-free model
      to study the kinetics of CYP27B1-dependent 1 alpha-hydroxylation of 25(OH)-19-nor
      D(3) and 25-hydroxyvitamin D(3) [25(OH)D(3)] and CYP24A1-dependent hydroxylation
      of 1 alpha,25(OH)-19-nor-D(3) and 1 alpha,25(OH)(2)D(3), we found that
      k(cat)/K(m) for 1 alpha-hydroxylation of 25(OH)-19-nor-D(3) was less than 0.1% of
      that for 25(OH)D(3), and the k(cat)/K(m) value for 24-hydroxylation was not
      significantly different between 1 alpha,25(OH)(2)-19-nor-D(3) and 1
      alpha,25(OH)(2)D(3). The data suggest a much slower formation and a similar rate
      of degradation of 1 alpha,25(OH)(2)-19-nor-D(3) compared with 1
      alpha,25(OH)(2)D(3). We then analyzed the metabolites of 25(OH)D(3) and 25(OH)-19
      nor-D(3) in PZ-HPV-7 cells by high-performance liquid chromatography. We found
      that a peak that comigrated with 1 alpha,25(OH)(2)D(3) was detected in cells
      incubated with 25(OH)D(3), whereas no 1 alpha,25(OH)(2)-19-nor-D(3) was detected
      in cells incubated with 25(OH)-19-nor-D(3). Thus, the present results do not
      support our previous hypothesis that 25(OH)-19-nor-D(3) is converted to 1
      alpha,25(OH)(2)-19-nor-D(3) by CYP27B1 in prostate cells to inhibit cell
      proliferation. We hypothesize that 25(OH)-19-nor-D(3) by itself may have a novel
      mechanism to activate vitamin D receptor or it is metabolized in prostate cells
      to an unknown metabolite with antiproliferative activity without 1 alpha
      hydroxylation. Thus, the results suggest that 25(OH)-19-nor-D(3) has potential as
      an attractive agent for prostate cancer therapy.

PMID- 17553916
TI  - Detection of haptenated proteins in organotypic human skin explant cultures
      exposed to dapsone.
AB  - Bioactivation of parent drug to reactive metabolite(s) followed by protein
      haptenation has been suggested to be a critical step in the elicitation of
      cutaneous drug reactions. Although liver is believed to be the primary organ of
      drug bioactivation quantitatively, other organs including skin may also
      metabolize drugs. Cultured human epidermal keratinocytes and dermal fibroblasts
      have been shown to be capable of bioactivating sulfonamides and sulfones, giving
      rise to haptenated proteins. It is, however, unclear whether metabolic events in
      these isolated cells reflect bioactivation in vivo. Hence, split-thickness human
      skin explants were exposed to dapsone (DDS) or its arylhydroxylamine metabolite
      (dapsone hydroxylamine, D-NOH) and probed for protein haptenation. DDS and D-NOH
      were applied either epicutaneously or mixed in the medium (to mimic its entry
      into skin from the systemic circulation). DDS-protein adducts were readily
      detected in skin explants exposed to either DDS or D-NOH. Adducts were detected
      mainly in the upper epidermal region in response to epicutaneous application,
      whereas adducts were formed all over the explants when DDS/D-NOH were mixed in
      the culture medium. In addition, adducts were visible in HLA-DR+ cells,
      indicating their presence in the dendritic cell population in the skin. Our
      results demonstrate the ability of intact human skin to bioactivate DDS leading
      to protein haptenation.

PMID- 17553917
TI  - Isolation and identification of phase 1 metabolites of demethoxycurcumin in rats.
AB  - Curcuminoids are a safe natural food coloring additive with anti-inflammatory,
      antioxidant, and anticarcinogenic activities. Although demethoxycurcumin is one
      of the major bioactive constituents of curcuminoids, knowledge about its
      metabolic fate is scant. In the present study, four new metabolites, 5-dehydroxy
      hexahydro-demethoxycurcumin-A (M-1), 5-dehydroxy-hexahydro-demethoxycurcumin-B (M
      2), 5-dehydroxy-octahydro-demethoxy-curcumin-A (M-3) and 5-dehydroxy-octahydro
      demethoxycurcumin-B (M-4), were isolated from feces of male Wistar-derived rats
      and from urine; three new metabolites, 5-O-methyl-hexahydrodemethoxycurcumin-A (M
      7), 5-O-methyl-hexahydro-demethoxycurcumin-B (M-8), and 5-dehydroxy-dihydro
      demethoxycurcumin-B (M-9), and two known metabolites, hexahydro-demethoxycurcumin
      A (M-5) and hexahydro-demethoxycurcumin-B (M-6), were isolated. Their structures
      were established by chemical and spectral methods. ll of them were reductive
      metabolites. Possibly of greater importance is that they occurred as pairs of
      isomers with a methoxyl group substituted on a different benzene ring. This
      finding in the metabolism of curcuminoids is reported here for the first time. In
      addition, the 5-dehydroxy or 5-O-methylated metabolites are also a novel finding.
      The fact that the metabolites occurred as pairs of the isomers suggests that
      demethoxycurcumin possibly undergoes tautomerization between 3-keto-5-enol (form
      A) and 3-keto-5-enol (form B) in rats. Based on the metabolite profiles,
      metabolic pathways of demethoxycurcumin in rats are proposed.

PMID- 17553918
TI  - Temporal and spatial gait characteristics of children with Hurler syndrome after
      umbilical cord blood transplantation.
AB  - BACKGROUND AND PURPOSE: Recent medical advances are increasing the life
      expectancy of children with Hurler syndrome; however, little is known about the
      motor abilities of children who have received these medical interventions. The
      purpose of this study was to describe the temporal and spatial gait parameters of
      children with Hurler syndrome following umbilical cord blood transplantation
      (UCBT) in reference to gait parameters of children with typical development.
      SUBJECTS: The group with Hurler syndrome consisted of 18 children between 19.6
      and 96.8 months of age who were examined 1 to 4 times between 2.9 and 72.2 months
      after UCBT. Four hundred thirty-eight children with typical development between
      the ages of 14.4 and 131.8 months served as a comparison group. METHODS: Temporal
      and spatial gait parameters were assessed using a GAITRite electronic walkway.
      Step length, gait speed, and cadence were normalized for body stature. RESULTS:
      Children with Hurler syndrome had slower gait speeds and shorter step lengths
      than children with typical development at 2 and 3 years of age. Time since
      transplantation was a predictor of gait speed and step length. DISCUSSION AND
      CONCLUSION: Children with Hurler syndrome after UCBT were delayed in maturation
      of temporal and spatial gait parameters.

PMID- 17553919
TI  - Plantar fasciitis: are pain and fascial thickness associated with arch shape and
      loading?
AB  - BACKGROUND AND PURPOSE: Although plantar fascial thickening is a sonographic
      criterion for the diagnosis of plantar fasciitis, the effect of local loading and
      structural factors on fascial morphology are unknown. The purposes of this study
      were to compare sonographic measures of fascial thickness and radiographic
      measures of arch shape and regional loading of the foot during gait in
      individuals with and without unilateral plantar fasciitis and to investigate
      potential relationships between these loading and structural factors and the
      morphology of the plantar fascia in individuals with and without heel pain.
      SUBJECTS: The participants were 10 subjects with unilateral plantar fasciitis and
      10 matched asymptomatic controls. METHODS: Heel pain on weight bearing was
      measured by a visual analog scale. Fascial thickness and static arch angle were
      determined from bilateral sagittal sonograms and weight-bearing lateral foot
      roentgenograms. Regional plantar loading was estimated from a pressure plate.
      RESULTS: On average, the plantar fascia of the symptomatic limb was thicker than
      the plantar fascia of the asymptomatic limb (6.1+/-1.4 mm versus 4.2+/-0.5 mm),
      which, in turn, was thicker than the fascia of the matched control limbs (3.4+/
      0.5 mm and 3.5+/-0.6 mm). Pain was correlated with fascial thickness, arch angle,
      and midfoot loading in the symptomatic foot. Fascial thickness, in turn, was
      positively correlated with arch angle in symptomatic and asymptomatic feet and
      with peak regional loading of the midfoot in the symptomatic limb. DISCUSSION AND
      CONCLUSION: The findings indicate that fascial thickness and pain in plantar
      fasciitis are associated with the regional loading and static shape of the arch.

PMID- 17553920
TI  - Neuromuscular electrical stimulation and volitional exercise for individuals with
      rheumatoid arthritis: a multiple-patient case report.
AB  - BACKGROUND AND PURPOSE: Muscle atrophy is common in patients with rheumatoid
      arthritis (RA). Although neuromuscular electrical stimulation (NMES) is a viable
      treatment for muscle atrophy, there is no evidence about the use of NMES in
      patients with RA. The purposes of this multiple-patient case report are: (1) to
      describe the use of NMES applied to the quadriceps femoris muscles in conjunction
      with an exercise program in patients with RA; (2) to report on patient tolerance
      and changes in lean muscle mass, quadriceps femoris muscle strength (force
      producing capacity), and physical function; and (3) to explore how changes in
      muscle mass relate to changes in quadriceps femoris muscle strength, measures of
      physical function, and patient adherence. CASE DESCRIPTION: Seven patients with
      RA (median age=61 years, range=39-80 years) underwent 16 weeks of NMES and
      volitional exercises. Lean muscle mass and strength of the quadriceps femoris
      muscle and physical function were measured before and after treatment. OUTCOMES:
      One patient did not tolerate the NMES treatment, and 2 patients did not complete
      at least half of the proposed treatment. Patients who completed the NMES and
      volitional exercise program increased their lean muscle mass, muscle strength,
      and physical function. DISCUSSION: Because of the small sample, whether NMES
      combined with exercises is better than exercise alone or NMES alone could not be
      determined. However, the outcomes from this multiple-patient case report indicate
      that NMES is a viable treatment option to address muscle atrophy and weakness in
      patients with RA. Strategies to increase tolerance and adherence to NMES are
      warranted.

PMID- 17553921
TI  - Variables influencing physical therapists' perceptions of continuing education.
AB  - BACKGROUND AND PURPOSE: As of October 1, 2002, physical therapy continuing
      education (CE) in Illinois was mandated. Research examining the recent mandate
      for physical therapists to engage in CE is limited. The purposes of this study
      were to examine the perceptions of physical therapist clinicians and managers
      concerning the barriers to and facilitators of CE and to identify how physical
      therapists perceive the role of their department in the CE process. SUBJECTS:
      Participants were 23 physical therapists at 6 hospitals. METHODS: Qualitative
      methodology was used to analyze data. RESULTS: Four themes were identified:
      negotiating and managing the variables associated with CE, providing and
      promoting opportunities that meet physical therapists' CE needs, identifying the
      elements of employment environments that foster CE, and perceived implications of
      mandating CE. DISCUSSION AND CONCLUSION: This investigation highlights the need
      to identify the core set of variables associated with engaging in CE and to
      promote the elements of employment environments that foster CE.

PMID- 17553922
TI  - Gait coordination after stroke: benefits of acoustically paced treadmill walking.
AB  - BACKGROUND AND PURPOSE: Gait coordination often is compromised after stroke. The
      purpose of this study was to evaluate the efficacy of acoustically paced
      treadmill walking as a method for improving gait coordination in people after
      stroke. PARTICIPANTS: Ten people after stroke volunteered for the study and
      comprised the experimental group. Nine elderly people who were healthy served as
      a control group. METHODS: Gait cycle parameters, interlimb coordination, and
      auditory-motor coordination were examined while participants walked on a
      treadmill with and without acoustic pacing. RESULTS: Stride frequency was
      adjusted to different acoustic pacing frequencies in all participants. In people
      after stroke, gait symmetry improved with acoustic pacing. They predominantly
      coordinated movements of the nonparetic limb to ipsilateral tones. DISCUSSION AND
      CONCLUSION: The results suggest that acoustically paced treadmill walking
      provides an effective means for immediately modifying stride frequency and
      improving gait coordination in people after stroke and, therefore, may be
      usefully applied in physical therapist practice. Future research directions for
      developing guidelines for using acoustically paced treadmill walking in physical
      therapist practice are discussed.

PMID- 17553923
TI  - A survey of therapeutic ultrasound use by physical therapists who are orthopaedic
      certified specialists.
AB  - BACKGROUND AND PURPOSE: For many years, ultrasound (US) has been a widely used
      and well-accepted physical therapy modality for the management of musculoskeletal
      conditions. However, there is a lack of scientific evidence on its effectiveness.
      This study examined the opinions of physical therapists with advanced competency
      in orthopedics about the use and perceived clinical importance of US in managing
      commonly encountered orthopedic impairments. SUBJECTS: Four hundred fifty-seven
      physical therapists who were orthopaedic certified specialists from the
      Northeast/Mid-Atlantic regions of the United States were invited to participate.
      METHODS: A 77-item survey instrument was developed. After face and content
      validity were established, the survey instrument was mailed to all subjects. Two
      hundred seven usable survey questionnaires were returned (response rate=45.3%).
      RESULTS: According to the surveys, the respondents indicated that they were
      likely to use US to decrease soft tissue inflammation (eg, tendinitis, bursitis)
      (83.6% of the respondents), increase tissue extensibility (70.9%), enhance scar
      tissue remodeling (68.8%), increase soft tissue healing (52.5%), decrease pain
      (49.3%), and decrease soft tissue swelling (eg, edema, joint effusion) (35.1%).
      The respondents used US to deliver medication (phonophoresis) for soft tissue
      inflammation (54.1%), pain management (22.2%), and soft tissue swelling (19.8%).
      The study provides summary data of the most frequently chosen machine parameters
      for duty cycle, intensity, and frequency. DISCUSSION AND CONCLUSION: Ultrasound
      continues to be a popular adjunctive modality in orthopedic physical therapy.
      These findings may help researchers prioritize needs for future research on the
      clinical effectiveness of US.

PMID- 17553924
TI  - Molecular analysis of the interaction of Bordetella pertussis adenylyl cyclase
      with fluorescent nucleotides.
AB  - The calmodulin (CaM)-dependent adenylyl cyclase (AC) toxin from Bordetella
      pertussis (CyaA) substantially contributes to the pathogenesis of whooping cough.
      Thus, potent and selective CyaA inhibitors may be valuable drugs for prophylaxis
      of this disease. We examined the interactions of fluorescent 2',3'-N
      methylanthraniloyl (MANT)-, anthraniloyl- and trinitrophenyl (TNP)-substituted
      nucleotides with CyaA. Compared with mammalian AC isoforms and Bacillus anthracis
      AC toxin edema factor, nucleotides inhibited catalysis by CyaA less potently.
      Introduction of the MANT substituent resulted in 5- to 170-fold increased potency
      of nucleotides. K(i) values of 3'MANT-2'd-ATP and 2'MANT-3'd-ATP in the AC
      activity assay using Mn(2+) were 220 and 340 nM, respectively. Natural nucleoside
      5'-triphosphates, guanine-, hypoxanthine- and pyrimidine-MANT- and TNP
      nucleotides and di-MANT nucleotides inhibited CyaA, too. MANT nucleotide binding
      to CyaA generated fluorescence resonance energy transfer (FRET) from tryptophans
      Trp69 and Trp242 and multiple tyrosine residues, yielding K(d) values of 300 nM
      for 3'MANT-2'd-ATP and 400 nM for 2'MANT-3'd-ATP. Fluorescence experiments and
      docking approaches indicate that the MANT- and TNP groups interact with Phe306.
      Increases of FRET and direct fluorescence with MANT nucleotides were strictly CaM
      dependent, whereas TNP nucleotide fluorescence upon binding to CyaA increased in
      the absence of CaM and was actually reduced by CaM. In contrast to low-affinity
      MANT nucleotides, even low-affinity TNP nucleotides generated strong fluorescence
      increases upon binding to CyaA. We conclude that the catalytic site of CyaA
      possesses substantial conformational freedom to accommodate structurally diverse
      ligands and that certain ligands bind to CyaA even in the absence of CaM,
      facilitating future inhibitor design.

PMID- 17553925
TI  - Cost-effectiveness of high-dose atorvastatin compared with usual-dose
      simvastatin: less than IDEAL?

PMID- 17553926
TI  - Straining to detect ischaemia.

PMID- 17553927
TI  - Evidence for coupled biogenesis of yeast Gap1 permease and sphingolipids:
      essential role in transport activity and normal control by ubiquitination.
AB  - Current models for plasma membrane organization integrate the emerging concepts
      that membrane proteins tightly associate with surrounding lipids and that
      biogenesis of surface proteins and lipids may be coupled. We show here that the
      yeast general amino acid permease Gap1 synthesized in the absence of sphingolipid
      (SL) biosynthesis is delivered to the cell surface but undergoes rapid and
      unregulated down-regulation. Furthermore, the permease produced under these
      conditions but blocked at the cell surface is inactive, soluble in detergent, and
      more sensitive to proteases. We also show that SL biogenesis is crucial during
      Gap1 production and secretion but that it is dispensable once Gap1 has reached
      the plasma membrane. Moreover, the defects displayed by cell surface Gap1
      neosynthesized in the absence of SL biosynthesis are not compensated by
      subsequent restoration of SL production. Finally, we show that down-regulation of
      Gap1 caused by lack of SL biogenesis involves the ubiquitination of the protein
      on lysines normally not accessible to ubiquitination and close to the membrane.
      We propose that coupled biogenesis of Gap1 and SLs would create an SL
      microenvironment essential to the normal conformation, function, and control of
      ubiquitination of the permease.

PMID- 17553928
TI  - Naked2 acts as a cargo recognition and targeting protein to ensure proper
      delivery and fusion of TGF-alpha containing exocytic vesicles at the lower
      lateral membrane of polarized MDCK cells.
AB  - Transforming growth factor-alpha (TGF-alpha) is the major autocrine EGF receptor
      ligand in vivo. In polarized epithelial cells, proTGF-alpha is synthesized and
      then delivered to the basolateral cell surface. We previously reported that
      Naked2 interacts with basolateral sorting determinants in the cytoplasmic tail of
      a Golgi-processed form of TGF-alpha and that TGF-alpha is not detected at the
      basolateral surface of Madin-Darby canine kidney (MDCK) cells expressing
      myristoylation-deficient (G2A) Naked2. By high-resolution microscopy, we now show
      that wild-type, but not G2A, Naked2-associated vesicles fuse at the plasma
      membrane. We further demonstrate that Naked2-associated vesicles are delivered to
      the lower lateral membrane of polarized MDCK cells independent of mu1B adaptin.
      We identify a basolateral targeting segment within Naked2; residues 1-173
      redirect NHERF-1 from the apical cytoplasm to the basolateral membrane, and
      internal deletion of residues 37-104 results in apical mislocalization of Naked2
      and TGF-alpha. Short hairpin RNA knockdown of Naked2 leads to a dramatic
      reduction in the 16-kDa cell surface isoform of TGF-alpha and increased cytosolic
      TGF-alpha immunoreactivity. We propose that Naked2 acts as a cargo recognition
      and targeting (CaRT) protein to ensure proper delivery, tethering, and fusion of
      TGF-alpha-containing vesicles to a distinct region at the basolateral surface of
      polarized epithelial cells.

PMID- 17553929
TI  - Multiple receptor interactions trigger release of membrane and intracellular
      calcium stores critical for herpes simplex virus entry.
AB  - Herpes simplex viruses (HSV) harness cellular calcium signaling pathways to
      facilitate viral entry. Confocal microscopy and small interfering RNA (siRNA)
      were used to identify the source of the calcium and to dissect the requisite
      viral-cell interactions. Binding of HSV to human epithelial cells induced no
      calcium response, but shifting the cells to temperatures permissive for
      penetration triggered increases in plasma membrane calcium followed by a global
      release of intracellular calcium. Transfection with siRNA targeting the
      proteoglycan syndecan-2 blocked viral binding and abrogated any calcium response.
      Transfection with siRNA targeting nectin-1, a glycoprotein D receptor, also
      prevented both membrane and intracellular calcium responses. In contrast, the
      membrane response was preserved after transfection with siRNA targeting
      integrinalphav, a novel glycoprotein H receptor. The membrane response, however,
      was not sufficient for viral entry, which required interactions with
      integrinalphav and release of inositol-triphosphate receptor-dependent
      intracellular calcium stores. Thus, calcium plays a critical, complex role in HSV
      entry.

PMID- 17553930
TI  - E-cadherin adhesion activates c-Src signaling at cell-cell contacts.
AB  - Cadherin-based cell-cell contacts are prominent sites for phosphotyrosine
      signaling, being enriched in tyrosine-phosphorylated proteins and tyrosine
      kinases and phosphatases. The functional interplay between cadherin adhesion and
      tyrosine kinase signaling, however, is complex and incompletely understood. In
      this report we tested the hypothesis that cadherin adhesion activates c-Src
      signaling and sought to assess its impact on cadherin function. We identified c
      Src as part of a cadherin-activated cell signaling pathway that is stimulated by
      ligation of the adhesion receptor. However, c-Src has a biphasic impact on
      cadherin function, exerting a positive supportive role at lower signal strengths,
      but inhibiting function at high signal strengths. Inhibiting c-Src under
      circumstances when it is activated by cadherin adhesion decreased several
      measures of cadherin function. This suggests that the cadherin-activated c-Src
      signaling pathway serves positively to support cadherin function. Finally, our
      data implicate PI3-kinase signaling as a target for cadherin-activated c-Src
      signaling that contributes to its positive impact on cadherin function. We
      conclude that E-cadherin signaling is an important activator of c-Src at cell
      cell contacts, providing a key input into a signaling pathway where quantitative
      changes in signal strength may result in qualitative differences in functional
      outcome.

PMID- 17553931
TI  - Poleward tubulin flux in spindles: regulation and function in mitotic cells.
AB  - The poleward flux of tubulin subunits through spindle microtubules is a striking
      and conserved phenomenon whose function and molecular components remain poorly
      understood. To screen for novel components of the flux machinery, we utilized RNA
      interference to deplete regulators of microtubule dynamics, individually and in
      various combinations, from S2 cells and examined the resulting impact on flux
      rate. This led to the identification of two previously unknown flux inhibitors,
      KLP59C and KLP67A, and a flux promoter, Mini-spindles. Furthermore, we find that
      flux rate is regulated by functional antagonism among microtubule stabilizers and
      destabilizers specifically at plus ends. Finally, by examining mitosis on
      spindles in which flux has been up- or down-regulated or restored after the
      codepletion of antagonistic flux regulators, we show that flux is an integral
      contributor to anaphase A but is not responsible for chromosome congression,
      interkinetochore tension, or the establishment of normal spindle length during
      prometaphase/metaphase.

PMID- 17553932
TI  - Parkin-mediated monoubiquitination of the PDZ protein PICK1 regulates the
      activity of acid-sensing ion channels.
AB  - Mutations in the parkin gene result in an autosomal recessive juvenile-onset form
      of Parkinson's disease. As an E3 ubiquitin-ligase, parkin promotes the attachment
      of ubiquitin onto specific substrate proteins. Defects in the ubiquitination of
      parkin substrates are therefore believed to lead to neurodegeneration in
      Parkinson's disease. Here, we identify the PSD-95/Discs-large/Zona Occludens-1
      (PDZ) protein PICK1 as a novel parkin substrate. We find that parkin binds PICK1
      via a PDZ-mediated interaction, which predominantly promotes PICK1
      monoubiquitination rather than polyubiquitination. Consistent with
      monoubiquitination and recent work implicating parkin in proteasome-independent
      pathways, parkin does not promote PICK1 degradation. However, parkin regulates
      the effects of PICK1 on one of its other PDZ partners, the acid-sensing ion
      channel (ASIC). Overexpression of wild-type, but not PDZ binding- or E3 ubiquitin
      ligase-defective parkin abolishes the previously described, protein kinase C
      induced, PICK1-dependent potentiation of ASIC2a currents in non-neuronal cells.
      Conversely, the loss of parkin in hippocampal neurons from parkin knockout mice
      unmasks prominent potentiation of native ASIC currents, which is normally
      suppressed by endogenous parkin in wild-type neurons. Given that ASIC channels
      contribute to excitotoxicity, our work provides a mechanism explaining how
      defects in parkin-mediated PICK1 monoubiquitination could enhance ASIC activity
      and thereby promote neurodegeneration in Parkinson's disease.

PMID- 17553933
TI  - Role of endosomal Na+-K+-ATPase and cardiac steroids in the regulation of
      endocytosis.
AB  - Plasma membrane Na(+)-K(+)-ATPase, which drives potassium into and sodium out of
      the cell, has important roles in numerous physiological processes. Cardiac
      steroids (CS), such as ouabain and bufalin, specifically interact with the pump
      and affect ionic homeostasis, signal transduction, and endocytosed membrane
      traffic. CS-like compounds are present in mammalian tissues, synthesized in the
      adrenal gland, and considered to be new family of steroid hormones. In this
      study, the mechanism of Na(+)-K(+)-ATPase involvement in the regulation of
      endocytosis is explored. We show that the effects of various CS on changes in
      endosomal pH are mediated by the pump and correspond to their effects on
      endosomal membrane traffic. In addition, it was found that CS-induced changes in
      endocytosed membrane traffic were dependent on alterations in [Na(+)] and [H(+)]
      in the endosome. Furthermore, we show that various CS differentially regulate
      endosomal pH and membrane traffic. The results suggest that these differences are
      due to specific binding characteristics. Based on our observations, we propose
      that Na(+)-K(+)-ATPase is a key player in the regulation of endosomal pH and
      endocytosed membrane traffic. Furthermore, our results raise the possibility that
      CS-like hormones regulate differentially intracellular membrane traffic.

PMID- 17553934
TI  - Na+-K+ pumps in the transverse tubular system of skeletal muscle fibers
      preferentially use ATP from glycolysis.
AB  - The Na(+)-K(+) pumps in the transverse tubular (T) system of a muscle fiber play
      a vital role keeping K(+) concentration in the T-system sufficiently low during
      activity to prevent chronic depolarization and consequent loss of excitability.
      These Na(+)-K(+) pumps are located in the triad junction, the key transduction
      zone controlling excitation-contraction (EC) coupling, a region rich in
      glycolytic enzymes and likely having high localized ATP usage and limited
      substrate diffusion. This study examined whether Na(+)-K(+) pump function is
      dependent on ATP derived via the glycolytic pathway locally within the triad
      region. Single fibers from rat fast-twitch muscle were mechanically skinned,
      sealing off the T-system but retaining normal EC coupling. Intracellular
      composition was set by the bathing solution and action potentials (APs) triggered
      in the T-system, eliciting intracellular Ca(2+) release and twitch and tetanic
      force responses. Conditions were selected such that increased Na(+)-K(+) pump
      function could be detected from the consequent increase in T-system polarization
      and resultant faster rate of AP repriming. Na(+)-K(+) pump function was not
      adequately supported by maintaining cytoplasmic ATP concentration at its normal
      resting level ( approximately 8 mM), even with 10 or 40 mM creatine phosphate
      present. Addition of as little as 1 mM phospho(enol)pyruvate resulted in a marked
      increase in Na(+)-K(+) pump function, supported by endogenous pyruvate kinase
      bound within the triad. These results demonstrate that the triad junction is a
      highly restricted microenvironment, where glycolytic resynthesis of ATP is
      critical to meet the high demand of the Na(+)-K(+) pump and maintain muscle
      excitability.

PMID- 17553935
TI  - Xenogenic macrophage immunization reduces atherosclerosis in apolipoprotein E
      knockout mice.
AB  - Atherosclerosis is a complex chronic inflammatory disease in which macrophages
      play a critical role, and the intervention of the inflammatory process in
      atherogenesis could be a therapeutic strategy. In this study, we investigated the
      efficacy of xenogenic macrophage immunization on the atherosclerotic lesion
      formation in a model of murine atherosclerosis. Apolipoprotein E knockout (apoE
      KO) mice were repeatedly immunized with formaldehyde-fixed cultured human
      macrophages (phorbol ester-stimulated THP-1 cells), using human serum albumin as
      a control protein or HepG2 cells as human control cells, once a week for four
      consecutive weeks. The vehicle phosphate-buffered saline was injected in the
      nonimmunized controls. THP-1 immunization induced antibodies that are
      immunoreactive with mouse macrophages. Although the plasma lipid levels were
      unchanged by the immunization, the atherosclerotic lesion area in the aortic root
      was significantly reduced by >50% in 16-wk-old THP-1-immunized apoE-KO mice
      compared with that in control mice. THP-1 immunization reduced in vivo macrophage
      infiltration, reduced in vitro macrophage adhesion, and changed cytokine
      production by macrophages to the antiatherogenic phenotype. Xenogenic macrophage
      immunization protects against the development of atherosclerosis in apoE-KO mice
      by modulating macrophage function in which antibodies induced by the immunization
      are likely to be involved. This method is a novel and potentially useful cell
      mediated immune therapeutic technique against atherosclerosis.

PMID- 17553936
TI  - High turnover of ezrin T567 phosphorylation: conformation, activity, and cellular
      function.
AB  - In its dormant state, the membrane cytoskeletal linker protein ezrin takes on a
      NH(2) terminal-to-COOH terminal (N-C) binding conformation. In vitro evidence
      suggests that eliminating the N-C binding conformation by Thr(567)
      phosphorylation leads to ezrin activation. Here, we found for resting gastric
      parietal cells that the levels of ezrin phosphorylation on Thr(567) are low and
      can be increased to a small extent ( approximately 40%) by stimulating secretion
      via the cAMP pathway. Treatment of cells with protein phosphatase inhibitors led
      to a rapid, dramatic increase in Thr(567) phosphorylation by 400% over resting
      levels, prompting the hypothesis that ezrin activity is regulated by turnover of
      phosphorylation on Thr(567). In vitro and in vivo fluorescence resonance energy
      transfer analysis demonstrated that Thr(567) phosphorylation opens the N-C
      interaction. However, even in the closed conformation, ezrin localizes to
      membranes by an exposed NH(2) terminal binding site. Importantly, the opened
      phosphorylated form of ezrin more readily cosediments with F-actin and binds more
      tightly to membrane than the closed forms. Furthermore, fluorescence recovery
      after photobleaching analysis in live cells showed that the Thr567Asp mutant had
      longer recovery times than the wild type or the Thr567Ala mutant, indicating the
      Thr(567)-phosphorylated form of ezrin is tightly associated with F-actin and the
      membrane, restricting normal activity. These data demonstrate and emphasize the
      functional importance of reversible phosphorylation of ezrin on F-actin binding.
      A novel model is proposed whereby ezrin and closely associated kinase and
      phosphatase proteins represent a motor complex to maintain a dynamic relationship
      between the varying membrane surface area and filamentous actin length.

PMID- 17553937
TI  - Estrogen receptor-alpha predominantly mediates the salutary effects of 17beta
      estradiol on splenic macrophages following trauma-hemorrhage.
AB  - Although 17beta-estradiol administration following trauma-hemorrhage prevents the
      suppression in splenic macrophage cytokine production, it remains unknown whether
      the salutary effects are mediated via estrogen receptor (ER)-alpha or ER-beta and
      which signaling pathways are involved in such 17beta-estradiol effects. Utilizing
      ER-alpha- or ER-beta-specific agonists, this study examined the role of ER-alpha
      and ER-beta in 17beta-estradiol-mediated restoration of macrophage cytokine
      production following trauma-hemorrhage. In addition, since MAPK and NF-kappaB are
      known to regulate macrophage cytokine production, we also examined the activation
      of those signaling molecules. Male rats underwent trauma-hemorrhage (mean
      arterial pressure of 40 mmHg for 90 min) and fluid resuscitation. The ER-alpha
      agonist propyl pyrazole triol (PPT; 5 microg/kg), the ER-beta agonist
      diarylpropionitrile (DPN; 5 microg/kg), 17beta-estradiol (50 microg/kg), or
      vehicle (10% DMSO) was injected subcutaneously during resuscitation. Twenty-four
      hours thereafter, splenic macrophages were isolated, and their IL-6 and TNF-alpha
      production and activation of MAPK and NF-kappaB were measured. Macrophage IL-6
      and TNF-alpha production and MAPK activation were decreased, whereas NF-kappaB
      activity was increased, following trauma-hemorrhage. PPT or 17beta-estradiol
      administration after trauma-hemorrhage normalized those parameters. DPN
      administration, on the other hand, did not normalize the above parameters. Since
      PPT but not DPN administration following trauma-hemorrhage was as effective as
      17beta-estradiol in preventing the suppression in macrophage cytokine production,
      it appears that ER-alpha plays the predominant role in mediating the salutary
      effects of 17beta-estradiol on macrophage cytokine production following trauma
      hemorrhage and that such effects are likely mediated via normalization of MAPK
      but not NF-kappaB signaling pathways.

PMID- 17553938
TI  - Cellular and subcellular distribution of the type-2 vasopressin receptor in the
      kidney.
AB  - Arginine vasopressin (AVP) is essential for maintaining body fluid homeostasis.
      The antidiuretic effects of AVP are initialized by binding of AVP to the type-2
      vasopressin receptor (V2R) in the kidney collecting duct (CD), resulting in the
      exocytic insertion of aquaporin-2 (AQP-2) water channels into the apical plasma
      membrane. In this study, we describe the generation and characterization of a
      polyclonal antibody targeted against the NH2 terminus of the rat V2R. HEK-293
      cells overexpressing the rat, mouse, or human V2R showed strong intracellular
      immunolabeling. Additionally, immunostaining of M-1 kidney cells expressing a V2R
      green fluorescent protein (GFP) fusion construct showed colocalization between
      GFP and antibody-specific V2R labeling. Immunoblots of rat kidney showed 43- and
      47-kDa proteins in all zones that were both reduced to 34-kDa by N-glycosidase F.
      Protein solubilization with nonionic detergents or the use of homobifunctional
      cross-linkers demonstrated that the rat V2R exists as a protein complex in native
      kidney. Immunohistochemistry of rat and mouse kidney revealed abundant labeling
      of the CD. Double-labeling confocal immunofluorescence microscopy [using distal
      convoluted tubule/connecting tubule (CNT)-specific marker calbindin and CNT/CD
      specific marker AQP-2] showed V2R labeling in both CD and CNT. There was a
      complete absence of labeling in vascular structures and other renal tubules,
      including the thick ascending limb (TAL), although RT-PCR of microdissected
      tubules showed expression of V2R mRNA in TAL. Confocal microscopy demonstrated
      that at the subcellular level, V2R labeling was predominantly intracellular in
      normal kidneys, although some staining was apparent in basolateral membrane
      domains. Confocal microscopy of isolated inner medullary collecting duct tubules
      showed that the V2R is expressed both intracellularly and in basolateral membrane
      domains.

PMID- 17553939
TI  - Novel sandwich ELISA for human angiotensinogen.
AB  - We recently reported that urinary excretion rates of angiotensinogen (U(AGT))
      provide a specific index of intrarenal renin-angiotensin (ANG) system (RAS)
      status in ANG II-dependent hypertensive rats. When this is shown to be applicable
      to human subjects, a diagnostic test to identify those hypertensive patients most
      likely to respond to an RAS blockade could provide useful information to allow a
      mechanistic rationale for selection of an optimized approach to treatment of
      hypertensive patients. However, simple and accurate methods to measure human
      angiotensinogen (hAGT) are unavailable. For future studies of human subjects, we
      developed antibodies and a sensitive and specific quantification system for hAGT
      using a sandwich ELISA. We raised two antibodies against hAGT: a mouse monoclonal
      antibody and a rabbit polyclonal antibody. The standard curve of this ELISA
      exhibited a high linearity (0.31-20 ng/ml). The correlation coefficient was
      >0.99. Plasma angiotensinogen concentrations of healthy volunteers ranged from 28
      to 71 microg/ml (n = 10). The ratio of U(AGT) to urinary creatinine concentration
      ranged from 5.0 to 30 microg/g (n = 7). Intra- and interassay coefficients of
      variation ranged from 4.4 to 5.5% and from 4.3 to 7.0%, respectively. This ELISA
      system had no cross-reactivity with major proteins in proteinuric urine samples,
      such as human albumin, immunoglobulin, or transferrin. Moreover, the cross
      reactivity of the system with angiotensin peptides was also negligible. This hAGT
      ELISA will be a useful tool to investigate the relationship of U(AGT) and
      reactivity to antihypertensive drugs in hypertensive patients.

PMID- 17553940
TI  - Calcium regulation of endothelin-1 synthesis in rat inner medullary collecting
      duct.
AB  - Collecting duct-derived endothelin-1 (ET-1) reduces blood pressure and inhibits
      Na and water reabsorption. Collecting duct ET-1 production is increased by volume
      expansion; however, the mechanism by which this occurs is unknown. We
      hypothesized that intracellular calcium, which is likely to be increased by
      volume expansion, regulates collecting duct ET-1 synthesis. Rat inner medullary
      collecting ducts (IMCD) were studied in primary culture. ET-1 release was
      decreased by 50-70% after chelation of intracellular calcium (BAPTA) or
      inhibition of CaM (W7) or CaMK (KN-93). These agents reduced ET-1 mRNA to a
      similar degree. CaM inhibition did not affect ET-1 mRNA stability. Transfection
      of IMCD with rat ET-1 promoter-luciferase constructs revealed maximal activity
      within 1.7 kb 5' to the transcription start site; 5, 20, 35, and 90% of this
      activity were in the 0.08-, 0.37-, 1.0-, and 3.0-kb promoter regions,
      respectively. W7 markedly inhibited activity of the 3.0-kb but not 0.37- or 1.0
      kb promoter regions. In contrast, W7 did not affect ET-1 release by rat aortic
      endothelial cells. Furthermore, transfected endothelial cells had maximal
      activity in the 0.37-kb region (as compared with the 1.7- and 3.0-kb regions),
      whereas W-7 had no effect on the activity of any of these promoter regions. In
      summary, IMCD ET-1 synthesis is regulated by calcium/CaM/CaMK-dependent pathways.
      The calcium/CaM-sensitive pathway is active in IMCD, but not endothelial cells.
      This suggests that IMCD-specific enhancer elements exist within the ET-1 promoter
      that confer unique calcium responsiveness.

PMID- 17553941
TI  - Changing motor synergies in chronic stroke.
AB  - Synergies are thought to be the building blocks of vertebrate movements. The
      inability to execute synergies in properly timed and graded fashion precludes
      adequate functional motor performance. In humans with stroke, abnormal synergies
      are a sign of persistent neurological deficit and result in loss of independent
      joint control, which disrupts the kinematics of voluntary movements. This study
      aimed at characterizing training-related changes in synergies apparent from
      movement kinematics and, specifically, at assessing: 1) the extent to which they
      characterize recovery and 2) whether they follow a pattern of augmentation of
      existing abnormal synergies or, conversely, are characterized by a process of
      extinction of the abnormal synergies. We used a robotic therapy device to train
      and analyze paretic arm movements of 117 persons with chronic stroke. In a task
      for which they received no training, subjects were better able to draw circles by
      discharge. Comparison with performance at admission on kinematic robot-derived
      metrics showed that subjects were able to execute shoulder and elbow joint
      movements with significantly greater independence or, using the clinical
      description, with more isolated control. We argue that the changes we observed in
      the proposed metrics reflect changes in synergies. We show that they capture a
      significant portion of the recovery process, as measured by the clinical Fugl
      Meyer scale. A process of "tuning" or augmentation of existing abnormal
      synergies, not extinction of the abnormal synergies, appears to underlie
      recovery.

PMID- 17553942
TI  - Differential effects of SNAP-25 deletion on Ca2+ -dependent and Ca2+ -independent
      neurotransmission.
AB  - At the synapse, SNAP-25, along with syntaxin/HPC-1 and synaptobrevin/VAMP, forms
      SNARE N-ethylmaleimide-sensitive factor [soluble (NSF) attachment protein
      receptor] complexes that are thought to catalyze membrane fusion. Results from
      neuronal cultures of synaptobrevin-2 knockout (KO) mice showed that loss of
      synaptobrevin has a more severe effect on calcium-evoked release than on
      spontaneous release or on release evoked by hypertonicity. In this study, we
      recorded neurotransmitter release from neuronal cultures of SNAP-25 KO mice to
      determine whether they share this property. In neurons lacking SNAP-25, as those
      deficient in synaptobrevin-2, we found that approximately 10-12% of calcium
      independent excitatory and inhibitory neurotransmitter release persisted.
      However, in contrast to synaptobrevin-2 knockouts, this remaining readily
      releasable pool in SNAP-25-deficient synapses was virtually insensitive to
      calcium-dependent-evoked stimulation. Although field stimulation reliably evoked
      neurotransmitter release in synaptobrevin-2 KO neurons, responses were rare in
      neurons lacking SNAP-25, and unlike synaptobrevin-2-deficient synapses, SNAP-25
      deficient synapses did not exhibit facilitation of release during high-frequency
      stimulation. This severe loss of evoked exocytosis was matched by a reduction,
      but not a complete loss, of endocytosis during evoked stimulation. Moreover,
      synaptic vesicle turnover probed by FM-dye uptake and release during hypertonic
      stimulation was relatively unaffected by the absence of SNAP-25. This last
      difference indicates that in contrast to synaptobrevin, SNAP-25 does not directly
      function in endocytosis. Together, these results suggest that SNAP-25 has a more
      significant role in calcium-secretion coupling than synaptobrevin-2.

PMID- 17553943
TI  - Superoxide (*O2- ) production in CA1 neurons of rat hippocampal slices exposed to
      graded levels of oxygen.
AB  - Neuronal signaling, plasticity, and pathologies in CA1 hippocampal neurons are
      all intimately related to the redox environment and, thus tissue oxygenation.
      This study tests the hypothesis that hyperoxic superfusate (95% O(2)) causes a
      time-dependent increase in superoxide anion (*O(2)(-)) production in CA1 neurons
      in slices, which will decrease as oxygen concentration is decreased. Hippocampal
      slices (400 microm) from weaned rats were incubated with the fluorescent probe
      dihydroethidium (DHE), which detects intracellular *O(2)(-) production. Slices
      were loaded for 30 min using 10 microM DHE and maintained using one-sided
      superfusion or continuously loaded using 2.5 microM DHE and maintained using two
      sided superfusion (36 degrees C). Continuous loading of DHE and two-sided
      superfusion gave the highest temporal resolution measurements of *O(2)(-)
      production, which was estimated by the increase in fluorescence intensity units
      (FIUs) per minute (FIU/min +/- SE) over 4 h. Superoxide production (2.5 microM
      DHE, 2-sided superfusion) was greatest in 95% O(2) (6.6 +/- 0.4 FIU/min) and
      decreased significantly during co-exposure with antioxidants (100 microM
      melatonin, 25 microM MnTMPyP) and lower levels of O(2) (60, 40, and 20% O(2) at
      5.3 +/- 0.3, 3.3 +/- 0.1, and 1.6 +/- 0.2 FIU/min, respectively). CA1 cell death
      after 4 h (ethidium homodimer-1 staining) was greatest in 95% O(2) and lowest in
      40 and 20% O(2). CA1 neurons generated evoked action potentials in 20% O(2) for
      >4 h, indicating viability at lower levels of oxygenation. We conclude that
      .O(2)(-) production and cell death in CA1 neurons increases in response to
      increasing oxygen concentration product (= PO(2) x time). Additionally, lower
      levels of oxygen (20-40%) and antioxidants should be considered to minimize
      superoxide-induced oxidative stress in brain slices.

PMID- 17553944
TI  - Retinogeniculate transmission in wakefulness.
AB  - Despite popular belief that the primary function of the thalamus is to "gate"
      sensory inputs by state, few studies have attempted to directly characterize the
      efficacy of such gating in the awake, behaving animal. I measured the efficacy of
      retinogeniculate transmission in the awake cat by taking advantage of the fact
      that many neurons in the lateral geniculate nucleus (LGN) are dominated by a
      single retinal input, and that this input produces a distinct event known as the
      S-potential. Retinal input failed to produce an LGN action potential half of the
      time. However, success or failure was powerfully tied to the recency of the S
      potential. Short intervals tend to be successful and long intervals unsuccessful.
      For four of 12 neurons, the probability that a given S-potential could cause a
      spike exceeded 90% if that S-potential was preceded by an S-potential within the
      previous 10 ms (100 Hz). Whereas this temporal influence on efficacy has been
      demonstrated extensively in anesthetized animals, wakefulness is different in
      several ways. Overall efficacy is better in wakefulness than in anesthesia, the
      durations of facilitating effects are briefer in wakefulness, efficacy of long
      intervals is superior in wakefulness, and the temporal dependence can be briefly
      disrupted by altering background illumination. The last two observations may be
      particularly significant. Increased success at long intervals in wakefulness
      provides additional evidence that the spike code of the anesthetized animal is
      not the spike code of the awake animal. Altering retinogeniculate efficacy by
      altering visual conditions undermines the influence inter-S-potential interval
      might have in determining efficacy in the real world. Finally, S-potential
      amplitude, duration, and even slope are dynamic and systematic within
      wakefulness; providing further support that the S-potential is the extracellular
      signature of the retinal EPSP.

PMID- 17553945
TI  - Action-potential-independent GABAergic tone mediated by nicotinic stimulation of
      immature striatal miniature synaptic transmission.
AB  - Stimulation of presynaptic nicotinic acetylcholine receptors (nAChRs) increases
      the frequency of miniature excitatory synaptic activity (mEPSCs) to a point where
      they can promote cell firing in hippocampal CA3 neurons. We have evaluated
      whether nicotine regulation of miniature synaptic activity can be extended to
      inhibitory transmission onto striatal medium spiny projection neurons (MSNs) in
      acute brain slices. Bath application of micromolar nicotine typically induced 12
      fold increases in the frequency of miniature inhibitory synaptic currents
      (mIPSCs). Little effect was observed on the amplitude of mIPSCs or mEPSCs under
      these conditions. Nicotine stimulation of mIPSCs was dependent on entry of
      extracellular calcium because removal of calcium from perfusate was able to block
      its action. To assess the potential physiological significance of the nicotine
      stimulated increase in mIPSC frequency, we also examined the nicotine effect on
      evoked IPSCs (eIPSCs). eIPSCs were markedly attenuated by nicotine. This effect
      could be attributed to two potential mechanisms: transmitter depletion due to
      extremely high mIPSC rates and/or a reduction in presynaptic excitability
      associated with nicotinic depolarization. Treatment with low concentrations of
      K(+) was able to in part mimic nicotine's stimulatory effect on mIPSCs and
      inhibitory effect on eIPSCs. Current-clamp recordings confirmed a direct
      depolarizing action of nicotine that could dampen eIPSC activity leading to a
      switch to striatal inhibitory synaptic transmission mediated by tonic mIPSCs.

PMID- 17553946
TI  - Biomechanical models for radial distance determination by the rat vibrissal
      system.
AB  - Rats use active, rhythmic movements of their whiskers to acquire tactile
      information about three-dimensional object features. There are no receptors along
      the length of the whisker; therefore all tactile information must be mechanically
      transduced back to receptors at the whisker base. This raises the question: how
      might the rat determine the radial contact position of an object along the
      whisker? We developed two complementary biomechanical models that show that the
      rat could determine radial object distance by monitoring the rate of change of
      moment (or equivalently, the rate of change of curvature) at the whisker base.
      The first model is used to explore the effects of taper and inherent whisker
      curvature on whisker deformation and used to predict the shapes of real rat
      whiskers during deflections at different radial distances. Predicted shapes
      closely matched experimental measurements. The second model describes the
      relationship between radial object distance and the rate of change of moment at
      the base of a tapered, inherently curved whisker. Together, these models can
      account for recent recordings showing that some trigeminal ganglion (Vg) neurons
      encode closer radial distances with increased firing rates. The models also
      suggest that four and only four physical variables at the whisker base -- angular
      position, angular velocity, moment, and rate of change of moment -- are needed to
      describe the dynamic state of a whisker. We interpret these results in the
      context of our evolving hypothesis that neural responses in Vg can be represented
      using a state-encoding scheme that includes combinations of these four variables.

PMID- 17553947
TI  - Studying the visual system in awake monkeys: two classic papers by Robert H.
      Wurtz.

PMID- 17553948
TI  - Measurement of reaching kinematics and prehensile dexterity in nonhuman primates.
AB  - A modified "Kluver" or dexterity board was developed to assess fine control of
      hand and digit movements by nonhuman primates during the acquisition of small
      food pellets from wells of different diameter. The primary advantages of the new
      device over those used previously include standardized positioning of target food
      pellets and controlled testing of each hand without the need for restraints,
      thereby allowing the monkey to move freely about the cage. Three-dimensional
      video analysis of hand motion was used to provide measures of reaching accuracy
      and grip aperture, as well as temporal measures of reach duration and food-pellet
      manipulation. We also present a validated performance score based on these
      measures, which serves as an indicator of successful food-pellet retrieval. Tests
      in three monkeys show that the performance score is an effective measure with
      which to study fine motor control associated with learning and handedness. We
      also show that the device and performance scores are effective for
      differentiating the effects of localized injury to motor areas of the cerebral
      cortex.

PMID- 17553949
TI  - Adaptation of voluntary saccades, but not of reactive saccades, transfers to hand
      pointing movements.
AB  - Studying the transfer of visuomotor adaptation from a given effector (e.g., the
      eye) to another (e.g., the hand) allows us to question whether sensorimotor
      processes influenced by adaptation are common to both effector control systems
      and thus to address the level where adaptation takes place. Previous studies have
      shown only very weak transfer of the amplitude adaptation of reactive saccades-
      i.e., produced automatically in response to the sudden appearance of visual
      targets--to hand pointing movements. Here we compared the amplitude of hand
      pointing movements recorded before and after adaptation of either reactive or
      voluntary saccades, produced either in a saccade sequence task or in a single
      saccade task. No transfer to hand pointing movements was found after adaptation
      of reactive saccades. In contrast, a substantial transfer to the hand was
      obtained following adaptation of voluntary saccades produced in sequence. Large
      amounts of transfer between the two saccade types were also found. These results
      demonstrate that the visuomotor processes influenced by saccadic adaptation
      depend on the type of saccades and that, in the case of voluntary saccades, they
      are shared by hand pointing movements. Implications for the neurophysiological
      substrates of the adaptation of reactive and voluntary saccades are discussed.

PMID- 17553950
TI  - Multidigit control of contact forces during transport of handheld objects.
AB  - When an object is lifted vertically, the normal force increases and decreases in
      tandem with tangential (load) force to safely avoid slips. For horizontal object
      transport, horizontal forces at the contact surfaces can be decomposed into
      manipulation forces (producing acceleration/deceleration) and grasping forces.
      Although the grasping forces must satisfy equilibrium constraints, it is not
      clear what determines their modulation across time, nor the extent to which they
      result from active muscle contraction or mechanical interactions of the digits
      with the moving object. Grasping force was found to increase in an experimental
      condition where the center of mass was below the contact plane, compared with
      when it was in the contact plane. This increase may be aimed at stabilizing
      object orientation during translation. In another experimental condition, more
      complex moments were introduced by allowing the low center of mass to swing
      around a pivot point. Electromyographic (EMG) activity recorded from several
      intrinsic and extrinsic hand muscles failed to reveal active feedback regulation
      of contact force in this situation. Instead, in all experimental conditions, EMG
      data revealed a strategy of feedforward stiffness modulation. Multiple regression
      analysis revealed that muscle activity at remote digits (e.g., the index and ring
      fingers) was highly correlated with the contact force measured at another digit
      (e.g., the thumb). The data suggest that to maintain grasp stability during
      horizontal translation, predictable as well as somewhat unpredictable inertial
      forces are compensated for by controlling the stiffness of the hand through
      cocontraction and modulation of hand muscle activity.

PMID- 17553951
TI  - Aging effects on the limits and stability of long-term synaptic potentiation and
      depression in rat hippocampal area CA1.
AB  - Altered hippocampal synaptic plasticity may underlie age-related memory
      impairment. In acute hippocampal slices from aged (22-24 mo) and young adult (1
      12 mo) male Brown Norway rats, extracellular excitatory postsynaptic field
      potentials were recorded in CA1 stratum radiatum evoked by Schaffer collateral
      stimulation. We used enhanced Ca(2+) to Mg(2+) ratio and paired-pulse stimulation
      protocol to induce maximum changes in the synaptic plasticity. Six episodes of
      theta-burst stimulation (TBS) or nine episodes of paired low-frequency
      stimulation (pLFS) were used to generate asymptotic long-term potentiation (LTP)
      and long-term depression (LTD), respectively. In addition, long-term
      depotentiation (LTdeP) or de-depression (LTdeD) from maximal LTP and LTD were
      examined using two episodes of pLFS or TBS. Multiple episodes of TBS or pLFS
      produced significant LTP or LTD in aged and young adult rats; this was not
      different between age groups. Moreover, there was no significant difference in
      the amount of LTdeP or LTdeD between aged and young adult rats. Our results show
      no age differences in the asymptotic magnitude of LTP or LTD, rate of synaptic
      modifications, development rates, reversal, or decay after postconditioning. Thus
      impairment of the basic synaptic mechanisms responsible for expression of these
      forms of plasticity is not likely to account for decline in memory function
      within this age range.

PMID- 17553952
TI  - Frames of reference for gaze saccades evoked during stimulation of lateral
      intraparietal cortex.
AB  - Previous studies suggest that stimulation of lateral intraparietal cortex (LIP)
      evokes saccadic eye movements toward eye- or head-fixed goals, whereas most
      single-unit studies suggest that LIP uses an eye-fixed frame with eye-position
      modulations. The goal of our study was to determine the reference frame for gaze
      shifts evoked during LIP stimulation in head-unrestrained monkeys. Two macaques
      (M1 and M2) were implanted with recording chambers over the right intraparietal
      sulcus and with search coils for recording three-dimensional eye and head
      movements. The LIP region was microstimulated using pulse trains of 300 Hz, 100
      150 microA, and 200 ms. Eighty-five putative LIP sites in M1 and 194 putative
      sites in M2 were used in our quantitative analysis throughout this study. Average
      amplitude of the stimulation-evoked gaze shifts was 8.67 degrees for M1 and 7.97
      degrees for M2 with very small head movements. When these gaze-shift trajectories
      were rotated into three coordinate frames (eye, head, and body), gaze endpoint
      distribution for all sites was most convergent to a common point when plotted in
      eye coordinates. Across all sites, the eye-centered model provided a
      significantly better fit compared with the head, body, or fixed-vector models
      (where the latter model signifies no modulation of the gaze trajectory as a
      function of initial gaze position). Moreover, the probability of evoking a gaze
      shift from any one particular position was modulated by the current gaze
      direction (independent of saccade direction). These results provide causal
      evidence that the motor commands from LIP encode gaze command in eye-fixed
      coordinates but are also subtly modulated by initial gaze position.

PMID- 17553953
TI  - Dopamine induces a slow afterdepolarization in lateral amygdala neurons.
AB  - The amygdala and dopaminergic innervation thereunto are considered to
      cooperatively regulate emotional states and behaviors. The present experiments
      examined effects of dopamine on lateral amygdala (LA) neuron excitability by
      whole cell recordings. Bath application of dopamine induced slow
      afterdepolarization (sADP). This sADP lasted for >5 s, and its magnitude varied
      in a concentration-dependent manner. Co-application of the D1 receptor antagonist
      SKF83566 reduced its amplitude. The D1 receptor agonist SKF38393, applied alone,
      induced sADP of a smaller amplitude. Induction of the full sADP required 5-HT(2)
      and noradrenalin alpha(1) receptor activation as well. D2 receptor activation or
      blockade did not affect sADP induction. The calcium channel blocker cadmium or
      intracellular calcium chelator bis-(o-aminophenoxy)-N,N,N',N' tetraacetic acid
      (BAPTA) blocked induction of the sADP, which was suggested to be triggered by
      calcium influx. Under voltage clamp, membrane conductance decreased at the peak
      of sADP current (I(sADP)). I(sADP) was suppressed by cesium included in pipettes.
      The I-V curve of the net I(sADP) was shifted as the external concentration of
      potassium was raised, and the reversal potential was identical to that of
      potassium, suggesting that dopamine decreases potassium conductance to induce the
      sADP. The present sADP may serve as a positive-feedback regulator of excitability
      in LA neurons.

PMID- 17553954
TI  - Target acceleration can be extracted and represented within the predictive drive
      to ocular pursuit.
AB  - Given sufficient exposure to stimulus presentation, the oculomotor system
      generates a representation of the stimulus characteristics, which is then used to
      predict the upcoming target motion. In addition to compensating for the
      perceptual-motor delay, these predictive processes perpetuate eye motion during a
      transient occlusion and compensate for the loss of visual input. At present,
      however, it is not well understood whether and how the oculomotor system extracts
      and represents target acceleration for subsequent predictive control. To this
      end, we used a target occlusion paradigm where both position and velocity of the
      target during the occlusion and at reappearance could not be predicted without
      extracting target acceleration before target disappearance. We found that the
      oculomotor response during the blanking period was not influenced by target
      acceleration when the initial exposure was 200 ms. However, smooth and saccadic
      eye movements did discriminate between the different levels of acceleration after
      an initial 500- or 800-ms exposure. In the event that the smooth response during
      the occlusion did not match well the target trajectory and thus eliminate a
      developing displacement error, there was an increased saccadic displacement.
      Still, the combined response during the blanking period did not eliminate retinal
      slip and position error at target reappearance. These results indicate that
      information on target acceleration can be extracted on-line, during pursuit of a
      visible ramp, and then used to drive a predictive oculomotor response in the
      absence of visual input.

PMID- 17553955
TI  - Contrasting interpretations of the nonuniform distribution of preferred
      directions within primary motor cortex.

PMID- 17553958
TI  - Riboswitching on RNA virus replication.
AB  - Positive-strand RNA viruses direct different virus-specific processes during
      their infection of host cells. Fundamental events such as viral RNA genome
      replication are controlled by viral regulatory RNA elements (REs). Here, we have
      investigated the possibility of specifically modulating the action of a viral RE
      using RNA aptamer technology. Through rational design, a tombusvirus RE, which
      has the structure of a perfect RNA stem loop in the plus-strand RNA genome, was
      replaced with a theophylline-binding RNA aptamer sequence, an imperfect stem
      loop. The aptamer-RE hybrid was designed so that, upon binding theophylline, it
      would become more stable and structurally mimic the functional RE (i.e.,
      represent a ligand-inducible RE riboswitch). Initial experiments were conducted
      with a small noncoding virus genome-derived RNA replicon, and the results showed
      that replication was inducible, up to approximately 10-fold, in a theophylline
      specific and dose-dependent manner. A similar level of theophylline-dependent
      induction was also observed when a full-length viral genome containing an RE
      riboswitch was tested. Analysis of this engineered viral genome revealed that
      this RE, located in the 5' untranslated region, specifically mediates efficient
      accumulation of plus-strands of the virus genome. Therefore, in addition to
      allowing for modulation of virus reproduction, the RE riboswitch system also
      provided insight into RE function. The ability to chemically induce a viral
      process via modulation of virus genome structure could be useful for basic and
      applied aspects of research.

PMID- 17553957
TI  - Inhibition of VEGF-A prevents the angiogenic switch and results in increased
      survival of Apc+/min mice.
AB  - Anti-VEGF-A monoclonal antibodies, in combination with chemotherapy, result in a
      survival benefit in patients with metastatic colorectal and non-small cell lung
      cancer, but little is known regarding the impact of anti-VEGF-A therapy on benign
      or premalignant tumors. The Apc+/min mice have been widely used as a model
      recapitulating early intestinal adenoma formation. To investigate whether tumor
      growth in Apc+/min mice is mediated by VEGF-A-dependent angiogenesis, we used two
      independent approaches to inhibit VEGF-A: monotherapy with a monoclonal antibody
      (Mab) targeting VEGF-A and genetic deletion of VEGF-A selectively in intestinal
      epithelial cells. Short-term (3 or 6 weeks) treatment with anti-VEGF-A Mab G6-31
      resulted in a nearly complete suppression of adenoma growth throughout the small
      intestine. Growth inhibition by Mab G6-31 was associated with a decrease in
      vascular density. Long-term (up to 52 weeks) treatment with Mab G6-31 led to a
      substantial increase in median survival. Deletion of VEGF-A in intestinal
      epithelial cells of Apc+/min mice yielded a significant inhibition of tumor
      growth, albeit of lesser magnitude than that resulting from Mab G6-31
      administration. These results establish that inhibition of VEGF-A signaling is
      sufficient for tumor growth cessation and confers a long-term survival benefit in
      an intestinal adenoma model. Therefore, VEGF-A inhibition may be a previously
      uncharacterized strategy for the prevention of the angiogenic switch and growth
      in intestinal adenomas.

PMID- 17553959
TI  - Selectivity and proofreading both contribute significantly to the fidelity of RNA
      polymerase III transcription.
AB  - We examine here the mechanisms ensuring the fidelity of RNA synthesis by RNA
      polymerase III (Pol III). Misincorporation could only be observed by using
      variants of Pol III deficient in the intrinsic RNA cleavage activity.
      Determination of relative rates of the reactions producing correct and erroneous
      transcripts at a specific position on a tRNA gene, combined with computational
      methods, demonstrated that Pol III has a highly efficient proofreading activity
      increasing its transcriptional fidelity by a factor of 10(3) over the error rate
      determined solely by selectivity (1.8 x 10(-4)). We show that Pol III slows down
      synthesis past a misincorporation to achieve efficient proofreading. We discuss
      our findings in the context of transcriptional fidelity studies performed on RNA
      Pols, proposing that the fidelity of transcription is more crucial for Pol III
      than Pol II.

PMID- 17553960
TI  - Regulation of the GABA cell phenotype in hippocampus of schizophrenics and
      bipolars.
AB  - GABAergic dysfunction is present in the hippocampus in schizophrenia (SZ) and
      bipolar disorder (BD). The trisynaptic pathway was "deconstructed" into various
      layers of sectors CA3/2 and CA1 and gene expression profiling performed. Network
      association analysis was used to uncover genes that may be related to regulation
      of glutamate decarboxylase 67 (GAD(67)), a marker for this system that has been
      found by many studies to show decreased expression in SZs and BDs. The most
      striking change was a down-regulation of GAD(67) in the stratum oriens (SO) of
      CA2/3 in both groups; CA1 only showed changes in the SO of schizophrenics. The
      network generated for GAD(67) contained 25 genes involved in the regulation of
      kainate receptors, TGF-beta and Wnt signaling, as well as transcription factors
      involved in cell growth and differentiation. In SZs, IL-1beta, (GRIK2/3), TGF
      beta2, TGF-betaR1, histone deacetylase 1 (HDAC1), death associated protein
      (DAXX), and cyclin D2 (CCND2) were all significantly up-regulated, whereas in
      BDs, PAX5, Runx2, LEF1, TLE1, and CCND2 were significantly down-regulated. In the
      SO of CA1 of BDs, where GAD67 showed no expression change, TGF-beta and Wnt
      signaling genes were all up-regulated, but other transcription factors showed no
      change in expression. In other layers/sectors, BDs showed no expression changes
      in these GAD(67) network genes. Overall, these results are consistent with the
      hypothesis that decreased expression of GAD(67) may be associated with an
      epigenetic mechanism in SZ. In BD, however, a suppression of transcription
      factors involved in cell differentiation may contribute to GABA dysfunction.

PMID- 17553961
TI  - Molecular sabotage of plant defense by aphid saliva.
AB  - Aphids, which constitute one of the most important groups of agricultural pests,
      ingest nutrients from sieve tubes, the photoassimilate transport conduits in
      plants. Aphids are able to successfully puncture sieve tubes with their piercing
      mouthparts (stylets) and ingest phloem sap without eliciting the sieve tubes'
      normal occlusion response to injury. Occlusion mechanisms are calcium-triggered
      and may be prevented by chemical constituents in aphid saliva injected into sieve
      tubes before and during feeding. We recorded aphid feeding behavior with the
      electrical penetration graph (EPG) technique and then experimentally induced
      sieve tube plugging. Initiation of sieve tube occlusion caused a change in aphid
      behavior from phloem sap ingestion to secretion of watery saliva. Direct proof of
      "unplugging" properties of aphid saliva was provided by the effect of aphid
      saliva on forisomes. Forisomes are proteinaceous inclusions in sieve tubes of
      legumes that show calcium-regulated changes in conformation between a contracted
      state (below calcium threshold) that does not occlude the sieve tubes and a
      dispersed state (above calcium threshold) that occludes the sieve tubes. We
      demonstrated in vitro that aphid saliva induces dispersed forisomes to revert
      back to the nonplugging contracted state. Labeling Western-blotted saliva
      proteins with 45Ca2+ or ruthenium red inferred the presence of calcium-binding
      domains. These results demonstrate that aphid saliva has the ability to prevent
      sieve tube plugging by molecular interactions between salivary proteins and
      calcium. This provides aphids with access to a continuous flow of phloem sap and
      is a critical adaptation instrumental in the evolutionary success of aphids.

PMID- 17553962
TI  - Loss of a quiescent niche but not follicle stem cells in the absence of bone
      morphogenetic protein signaling.
AB  - During the hair cycle, follicle stem cells (SCs) residing in a specialized niche
      called the "bulge" undergo bouts of quiescence and activation to cyclically
      regenerate new hairs. Developmental studies have long implicated the canonical
      bone morphogenetic protein (BMP) pathway in hair follicle (HF) determination and
      differentiation, but how BMP signaling functions in the hair follicle SC niche
      remains unknown. Here, we use loss and gain of function studies to manipulate BMP
      signaling in the SC niche. We show that when the Bmpr1a gene is conditionally
      ablated, otherwise quiescent SCs are activated to proliferate, causing an
      expansion of the niche and loss of slow-cycling cells. Surprisingly, follicle SCs
      are not lost, however, but rather, they generate long-lived, tumor-like branches
      that express Sox4, Lhx2, and Sonic Hedgehog but fail to terminally differentiate
      to make hair. A key component of BMPR1A-deficient SCs is their elevated levels of
      both Lef1 and beta-catenin, which form a bipartite transcription complex required
      for initiation of the hair cycle. Although beta-catenin can be stabilized by Wnt
      signaling, we show that BMPR1A deficiency enhances beta-catenin stabilization in
      the niche through a pathway involving PTEN inhibition and PI3K/AKT activation.
      Conversely, sustained BMP signaling in the SC niche blocks activation and
      promotes premature hair follicle differentiation. Together, these studies reveal
      the importance of balancing BMP signaling in the SC niche.

PMID- 17553963
TI  - Relative resource abundance explains butterfly biodiversity in island
      communities.
AB  - Ecologists have long been intrigued by the factors that control the pattern of
      biodiversity, i.e., the distribution and abundance of species. Previous studies
      have demonstrated that coexisting species partition their resources and/or that
      the compositional similarity between communities is determined by environmental
      factors, lending support to the niche-assembly model. However, no attempt has
      been made to test whether the relative amount of resources that reflects relative
      niche space controls relative species abundance in communities. Here, we
      demonstrate that the relative abundance of butterfly species in island
      communities is significantly related to the relative biomasses of their host
      plants but not to the geographic distance between communities. In the studied
      communities, the biomass of particular host plant species positively affected the
      abundance of the butterfly species that used them, and consequently, influenced
      the relative abundance of the butterfly communities. This indicated that the
      niche space of butterflies (i.e., the amount of resources) strongly influences
      butterfly biodiversity patterns. We present this field evidence of the niche
      apportionment model that propose that the relative amount of niche space explains
      the pattern of the relative abundance of the species in communities.

PMID- 17553964
TI  - Dendritic BC200 RNA in aging and in Alzheimer's disease.
AB  - Small untranslated BC1 and BC200 RNAs are translational regulators that are
      selectively targeted to somatodendritic domains of neurons. They are thought to
      operate as modulators of local protein synthesis in postsynaptic dendritic
      microdomains, in a capacity in which they would contribute to the maintenance of
      long-term synaptic plasticity. Because plasticity failure has been proposed to be
      a starting point for the neurodegenerative changes that are seen in Alzheimer's
      disease (AD), we asked whether somatodendritic levels of human BC200 RNA are
      deregulated in AD brains. We found that in normal aging, BC200 levels in cortical
      areas were reduced by >60% between the ages of 49 and 86. In contrast, BC200 RNA
      was significantly up-regulated in AD brains, in comparison with age-matched
      normal brains. This up-regulation in AD was specific to brain areas that are
      involved in the disease. Relative BC200 levels in those areas increased in
      parallel with the progression of AD, as reflected by Clinical Dementia Rating
      scores. In more advanced stages of the disease, BC200 RNA often assumed a
      clustered perikaryal localization, indicating that dendritic loss is accompanied
      by somatic overexpression. Mislocalization and overexpression of BC200 RNA may be
      reactive-compensatory to, or causative of, synaptodendritic deterioration in AD
      neurons.

PMID- 17553965
TI  - Generation of DNA cleavage specificities of type II restriction endonucleases by
      reassortment of target recognition domains.
AB  - Type II restriction endonucleases (REases) cleave double-stranded DNA at specific
      sites within or close to their recognition sequences. Shortly after their
      discovery in 1970, REases have become one of the primary tools in molecular
      biology. However, the list of available specificities of type II REases is
      relatively short despite the extensive search for them in natural sources and
      multiple attempts to artificially change their specificity. In this study, we
      examined the possibility of generating cleavage specificities of REases by
      swapping putative target recognition domains (TRDs) between the type IIB enzymes
      AloI, PpiI, and TstI. Our results demonstrate that individual TRDs recognize
      distinct parts of the bipartite DNA targets of these enzymes and are
      interchangeable. Based on these properties, we engineered a functional type IIB
      REase having previously undescribed DNA specificity. Our study suggests that the
      TRD-swapping approach may be used as a general technique for the generation of
      type II enzymes with predetermined specificities.

PMID- 17553966
TI  - Automated reverse engineering of nonlinear dynamical systems.
AB  - Complex nonlinear dynamics arise in many fields of science and engineering, but
      uncovering the underlying differential equations directly from observations poses
      a challenging task. The ability to symbolically model complex networked systems
      is key to understanding them, an open problem in many disciplines. Here we
      introduce for the first time a method that can automatically generate symbolic
      equations for a nonlinear coupled dynamical system directly from time series
      data. This method is applicable to any system that can be described using sets of
      ordinary nonlinear differential equations, and assumes that the (possibly noisy)
      time series of all variables are observable. Previous automated symbolic modeling
      approaches of coupled physical systems produced linear models or required a
      nonlinear model to be provided manually. The advance presented here is made
      possible by allowing the method to model each (possibly coupled) variable
      separately, intelligently perturbing and destabilizing the system to extract its
      less observable characteristics, and automatically simplifying the equations
      during modeling. We demonstrate this method on four simulated and two real
      systems spanning mechanics, ecology, and systems biology. Unlike numerical
      models, symbolic models have explanatory value, suggesting that automated
      "reverse engineering" approaches for model-free symbolic nonlinear system
      identification may play an increasing role in our ability to understand
      progressively more complex systems in the future.

PMID- 17553967
TI  - Long-term monitoring of transplanted human neural stem cells in developmental and
      pathological contexts with MRI.
AB  - Noninvasive monitoring of stem cells, using high-resolution molecular imaging,
      will be instrumental to improve clinical neural transplantation strategies. We
      show that labeling of human central nervous system stem cells grown as
      neurospheres with magnetic nanoparticles does not adversely affect survival,
      migration, and differentiation or alter neuronal electrophysiological
      characteristics. Using MRI, we show that human central nervous system stem cells
      transplanted either to the neonatal, the adult, or the injured rodent brain
      respond to cues characteristic for the ambient microenvironment resulting in
      distinct migration patterns. Nanoparticle-labeled human central nervous system
      stem cells survive long-term and differentiate in a site-specific manner
      identical to that seen for transplants of unlabeled cells. We also demonstrate
      the impact of graft location on cell migration and describe magnetic resonance
      characteristics of graft cell death and subsequent clearance. Knowledge of
      migration patterns and implementation of noninvasive stem cell tracking might
      help to improve the design of future clinical neural stem cell transplantation.

PMID- 17553968
TI  - Dissociation of halted T7 RNA polymerase elongation complexes proceeds via a
      forward-translocation mechanism.
AB  - A recent model for the mechanism of intrinsic transcription termination involves
      dissociation of the RNA from forward-translocated (hypertranslocated) states of
      the complex [Yarnell WS, Roberts JW (1999) Science, 284:611-615]. The current
      study demonstrates that halted elongation complexes of T7 RNA polymerase in the
      absence of termination signals can also dissociate via a forward-translocation
      mechanism. Shortening of the downstream DNA or the introduction of a stretch of
      mismatched DNA immediately downstream of the halt site reduces a barrier to
      forward translocation and correspondingly reduces the lifetime of halted
      complexes. Conversely, introduction of a cross-link downstream of the halt site
      increases the same barrier and leads to an increase in complex lifetime.
      Introduction of a mismatch within the bubble reduces a driving force for forward
      translocation and correspondingly increases the lifetime of the complex, but only
      for mismatches at the upstream edge of the bubble, as predicted by the model.
      Mismatching only the two most upstream of the eight bases in the bubble provides
      a maximal increase in complex stability, suggesting that dissociation occurs
      primarily from early forward-translocated states. Finally, addition in trans of
      an oligonucleotide complementary to the nascent RNA just beyond the hybrid
      complements the loss of driving force derived from placement of a mismatch within
      the bubble, confirming the expected additivity of effects. Thus, forward
      translocation is likely a general mechanism for dissociation of elongation
      complexes, both in the presence and absence of intrinsic termination signals.

PMID- 17553969
TI  - Shelf life of predosed plates containing mefloquine, artemisinin,
      dihydroartemisinin, and artesunate as used for in vitro Plasmodium falciparum
      susceptibility assessment.
AB  - The shelf lives of preserved antimalarial agent-predosed plates according to the
      type of wrapping and the temperature of storage were studied by measuring the 50%
      inhibitory concentrations of drug for Plasmodium falciparum 3D7. The shelf life
      of mefloquine was 8 weeks at 25 degrees C; and those of artesunate, artemisinin,
      and dihydroartemisinin were a minimum of 24, 12, and 8 weeks, respectively, at 4
      degrees C.

PMID- 17553971
TI  - Evaluation of a new chromogenic medium, ChromID VRE, for detection of vancomycin
      resistant Enterococci in stool samples and rectal swabs.
AB  - We compared ChromID VRE medium with Enterococcosel containing vancomycin for the
      detection of vancomycin-resistant Enterococcus in 1,007 specimens. ChromID VRE in
      combination with Gram straining provided a higher specificity than
      Enterococcosel, irrespective of the incubation time and enrichment.

PMID- 17553970
TI  - Gray foxes (Urocyon cinereoargenteus) as a potential reservoir of a Bartonella
      clarridgeiae-like bacterium and domestic dogs as part of a sentinel system for
      surveillance of zoonotic arthropod-borne pathogens in northern California.
AB  - Two species of Bartonella, a novel Bartonella clarridgeiae-like bacterium and B.
      vinsonii subsp. berkhoffii, were isolated from rural dogs and gray foxes in
      northern California. A novel B. clarridgeiae-like species was isolated from 3
      (1.7%) of 182 dogs and 22 (42%) of 53 gray foxes, while B. vinsonii subsp.
      berkhoffii was isolated from 1 dog (0.5%) and 5 gray foxes (9.4%). PCR and DNA
      sequence analyses of the citrate synthase (gltA) gene and the 16S-23S intergenic
      spacer region suggested that strains infecting dogs and gray foxes were
      identical. Fifty-four dogs (29%) and 48 gray foxes (89%) had reciprocal titers of
      antibodies against Bartonella spp. of > or =64. The high prevalence of bacteremia
      and seroreactivity to Bartonella spp. in gray foxes suggests that they may act as
      a reservoir species for the B. clarridgeiae-like species in this region. Domestic
      dogs were also tested for other arthropod-borne infectious agents. Fifty-one dogs
      (28%) were positive for Dirofilaria immitis antigen, seventy-four (40%) were
      seroreactive to Anaplasma phagocytophilum, and five (2.7%) were seropositive for
      Yersinia pestis. Fourteen dogs (7.6%) were PCR positive for A. phagocytophilum.
      Polytomous logistic regression models were used to assess the association of
      Bartonella antibody titer categories with potential risk factors and the presence
      of other vector-borne agents in domestic dogs. Older dogs were more likely to be
      seroreactive to Bartonella spp. There was no association between the exposure of
      dogs to Bartonella and the exposure of dogs to A. phagocytophilum in this study.

PMID- 17553972
TI  - Molecular characterization and distribution of genes encoding members of the type
      III effector nleA family among pathogenic Escherichia coli strains.
AB  - In this study, we investigated the occurrence of the previously described gene
      nleA(4795) and variants of nleA, putatively encoding non-locus-of-enterocyte
      effacement-encoded type III effector proteins with functions that are unknown.
      nleA variants were detected in 150 out of 170 enteropathogenic Escherichia coli
      strains and enterohemorrhagic E. coli strains, two of them being eae negative.
      Besides the known variants nleA(4795), Z6024, and the espI-like gene, 11 novel
      nleA variants with different lengths and sequence identities at the deduced amino
      acid level (between 71% and 96%) have been identified. Whereas most of the
      serogroups associated with more severe disease were quite homogenous with respect
      to the presence of a particular nleA variant, other serogroups were not.
      Moreover, Southern blot hybridization revealed that certain strains carry two
      copies of nleA in their chromosome, frequently encoding different variants. In
      most cases, the open reading frame of one of the copies was disrupted, usually by
      an insertion element. Furthermore, transmission of the type III effector-encoding
      gene could be shown by transduction of nleA-carrying bacteriophages to a
      laboratory E. coli strain.

PMID- 17553973
TI  - Development of multiple-locus variable-number tandem-repeat analysis for Yersinia
      enterocolitica subsp. palearctica and its application to bioserogroup 4/O3
      subtyping.
AB  - Yersinia enterocolitica bioserogroup 4/O3 is the predominant causative agent of
      yersiniosis in Europe and North America. Multiple-locus variable-number tandem
      repeat analysis (MLVA) was developed to improve the resolution power of classical
      genotyping methods. MLVA based on six loci was able to distinguish 76 genotypes
      among 91 Y. enterocolitica isolates of worldwide origin and 41 genotypes among 51
      nonepidemiologically linked bioserogroup 4/O3 isolates, proving that it has a
      high resolution power. However, only a slight correlation of the MLVA genotypes
      and the geographic distribution of the isolates was observed. Although MLVA was
      also capable of distinguishing strains of Y. enterocolitica subsp. palearctica O9
      and O5,27, there was only a minor correlation between the MLVA genotypes and
      serogroups. MLVA may be a helpful tool for epidemiological investigations of Y.
      enterocolitica subsp. palearctica outbreaks.

PMID- 17553974
TI  - Rapid identification of viridans streptococci by mass spectrometric
      discrimination.
AB  - Viridans streptococci (VS) are responsible for several systemic diseases, such as
      endocarditis, abscesses, and septicemia. Unfortunately, species identification by
      conventional methods seems to be more difficult than species identification of
      other groups of bacteria. The aim of the present study was to evaluate the use of
      cell matrix-assisted laser desorption ionization-time of flight mass spectrometry
      (MALDI-TOF-MS) for the rapid identification of 10 different species of VS. A
      total of 99 VS clinical isolates, 10 reference strains, and 20 strains from our
      in-house culture collection were analyzed by MALDI-TOF-MS. To evaluate the mass
      spectrometric discrimination results, all strains were identified in parallel by
      phenotypic and genotypic methods. MALDI-TOF-MS identified 71 isolates as the
      mitis group, 23 as the anginosus group, and 5 as Streptococcus salivarius.
      Comparison of the species identification results obtained by the MALDI-TOF-MS
      analyses and with the phenotypic/genotypic identification systems showed 100%
      consistency at the species level. Thus, MALDI-TOF-MS seems to be a rapid and
      reliable method for the identification of species of VS from clinical samples.

PMID- 17553976
TI  - Nuclease-resistant single-stranded DNA controls for nucleic acid amplification
      assays.
AB  - Molecular diagnostic tests based on the PCR or alternative nucleic acid
      amplification technologies are commonly used for pathogen screening at blood
      drawing centers. Contrived process surveillance using test-specific external and
      internal controls is critical for the efficient leverage of PCR power. We
      describe here novel control constructs for use in nucleic acid amplification
      assays for pathogens with a single-stranded DNA genome, e.g., parvovirus B19.
      These controls are derived from a deletion mutant of the filamentous phage fd
      tet, fKN16, and consist of single-stranded DNA packaged in a protein coat. They
      are essentially noninfectious to Escherichia coli and highly resistant to
      nuclease degradation. fKN16 based controls can be readily manufactured and highly
      purified. Despite their confirmed filamentous morphology, they can be precisely
      and accurately diluted over a wide range. Stability studies reveal that the novel
      control constructs are highly resistant to temperature stress, regardless of
      whether they are tested as concentrated stocks in storage buffer or diluted in
      buffer or human plasma. Real-time amplification curves derived from recombinant
      control constructs containing a parvovirus B19 specific sequence fragment match
      those derived from native virus. In summary, our data demonstrate the feasibility
      of novel nuclease-resistant single-stranded DNA controls as surrogates for
      parvovirus B19 and their applicability in routine molecular diagnostics.

PMID- 17553975
TI  - Assessment of Candida glabrata strain relatedness by pulsed-field gel
      electrophoresis and multilocus sequence typing.
AB  - In this study, 80 Candida glabrata isolates from intensive care unit and human
      immunodeficiency virus (HIV)-infected patients were typed by multilocus sequence
      typing (MLST), pulsed-field gel electrophoresis (PFGE), and mating type class
      determination. Among the 25 patients with multiple isolates, 19 patients (76%)
      contained multiple isolates exhibiting identical or highly related PFGE and MLST
      genotypes, which may indicate the maintenance or microvariation of one C.
      glabrata strain in each patient. However, isolates from six patients (24%)
      displayed different sequence types, PFGE genotypes, or mating type classes, which
      may indicate colonization with more than one clone over time or strain
      replacement. High correlations among PFGE genotypes, sequence types, and mating
      types were found (P < 0.01). MLST exhibited less discriminatory power than PFGE
      with BssHII. The genotypes, sequence types, and mating type classes were
      independent of anatomic sources, drug susceptibility, and HIV infection status.

PMID- 17553977
TI  - Molecular typing of isolates of Rickettsia rickettsii by use of DNA sequencing of
      variable intergenic regions.
AB  - Rickettsia rickettsii, the causative agent of Rocky Mountain spotted fever, is
      found throughout the Americas, where it is associated with different animal
      reservoirs and tick vectors. No molecular typing system currently exists to allow
      for the robust differentiation of isolates of R. rickettsii. Analysis of eight
      completed genome sequences of rickettsial species revealed a high degree of
      sequence conservation within the coding regions of chromosomes in the genus.
      Intergenic regions between coding sequences should be under less selective
      pressure to maintain this conservation and thus should exhibit greater nucleotide
      polymorphisms. Utilizing these polymorphisms, we developed a molecular typing
      system that allows for the genetic differentiation of isolates of R. rickettsii.
      This typing system was applied to a collection of 38 different isolates collected
      from humans, animals, and tick vectors from different geographic locations.
      Serotypes 364D, from Dermacentor occidentalis ticks, and Hlp, from Haemaphysalis
      leporispalustris ticks, appear to be distinct genotypes that may not belong to
      the species R. rickettsii. We were also able to differentiate 36 historical
      isolates of R. rickettsii into three different phylogenetic clades containing
      seven different genotypes. This differentiation correlated well, but not
      perfectly, with the geographic origin and likely tick vectors associated with the
      isolates. The few apparent typing discrepancies found suggest that the molecular
      ecology of R. rickettsii needs more investigation.

PMID- 17553979
TI  - Target selection: choice or response?

PMID- 17553980
TI  - Awfully afraid? Dissociating decision- from motor- and sensory-related brain
      activation during perceptual choices.

PMID- 17553978
TI  - Detection of respiratory viruses and subtype identification of influenza A
      viruses by GreeneChipResp oligonucleotide microarray.
AB  - Acute respiratory infections are significant causes of morbidity, mortality, and
      economic burden worldwide. An accurate, early differential diagnosis may alter
      individual clinical management as well as facilitate the recognition of outbreaks
      that have implications for public health. Here we report on the establishment and
      validation of a comprehensive and sensitive microarray system for detection of
      respiratory viruses and subtyping of influenza viruses in clinical materials.
      Implementation of a set of influenza virus enrichment primers facilitated
      subtyping of influenza A viruses through the differential recognition of
      hemagglutinins 1 through 16 and neuraminidases 1 through 9. Twenty-one different
      respiratory virus species were accurately characterized, including a recently
      identified novel genetic clade of rhinovirus.

PMID- 17553981
TI  - Temporal activity patterns in thermosensory neurons of freely moving
      Caenorhabditis elegans encode spatial thermal gradients.
AB  - Our understanding of the operation of neurons and neuronal circuits has come
      primarily from probing their activity in dissected, anesthetized, or restrained
      animals. However, the behaviorally relevant operation of neurons and neuronal
      circuits occurs within intact animals as they freely perform behavioral tasks.
      The small size and transparency of the nematode Caenorhabditis elegans make it an
      ideal system for noninvasive, optical measurements of neuronal activity. Here, we
      use a high signal-to-noise version of cameleon, a fluorescent calcium-binding
      protein, to quantify the activity of the AFD thermosensory neuron of individual
      worms freely navigating spatial thermal gradients. We find that AFD activity is
      directly coupled to the worm's exploratory movements in spatial thermal
      gradients. We show that the worm is able, in principle, to evaluate and guide its
      own thermotactic behaviors with respect to ambient spatial thermal gradients by
      monitoring the activity of this single thermosensory neuron.

PMID- 17553982
TI  - Transformation of temporal properties between auditory midbrain and cortex in the
      awake Mongolian gerbil.
AB  - The neural representation of meaningful stimulus features is thought to rely on
      precise discharge characteristics of the auditory cortex. Precisely timed onset
      spikes putatively carry the majority of stimulus-related information in auditory
      cortical neurons but make a small contribution to stimulus representation in the
      auditory midbrain. Because these conclusions derive primarily from anesthetized
      preparations, we reexamined temporal coding properties of single neurons in the
      awake gerbil inferior colliculus (IC) and compared them with primary auditory
      cortex (AI). Surprisingly, AI neurons displayed a reduction of temporal precision
      compared with those in the IC. Furthermore, this hierarchical transition from
      high to low temporal fidelity was observed for both static and dynamic stimuli.
      Because most of the data that support temporal precision were obtained under
      anesthesia, we also reexamined response properties of IC and AI neurons under
      these conditions. Our results show that anesthesia has profound effects on the
      trial-to-trial variability and reliability of discharge and significantly
      improves the temporal precision of AI neurons to both tones and amplitude
      modulated stimuli. In contrast, IC temporal properties are only mildly affected
      by anesthesia. These results underscore the pitfalls of using anesthetized
      preparations to study temporal coding. Our findings in awake animals reveal that
      AI neurons combine faster adaptation kinetics and a longer temporal window than
      evident in IC to represent ongoing acoustic stimuli.

PMID- 17553983
TI  - Coupling of neuronal nitric oxide synthase to NMDA receptors via postsynaptic
      density-95 depends on estrogen and contributes to the central control of adult
      female reproduction.
AB  - Considerable research has been devoted to the understanding of how nitric oxide
      (NO) influences brain function. Few studies, however, have addressed how its
      production is physiologically regulated. Here, we report that protein-protein
      interactions between neuronal NO synthase (nNOS) and glutamate NMDA receptors via
      the scaffolding protein postsynaptic density-95 (PSD-95) in the hypothalamic
      preoptic region of adult female rats is sensitive to cyclic estrogen fluctuation.
      Coimmunoprecipitation experiments were used to assess the physical association
      between nNOS and NMDA receptor NR2B subunit in the preoptic region of the
      hypothalamus. We found that nNOS strongly interacts with NR2B at the onset of the
      preovulatory surge at proestrus (when estrogen levels are highest) compared with
      basal-stage diestrous rats. Consistently, estrogen treatment of gonadectomized
      female rats also increases nNOS/NR2B complex formation. Moreover, endogenous
      fluctuations in estrogen levels during the estrous cycle coincide with changes in
      the physical association of nNOS to PSD-95 and the magnitude of NO release in the
      preoptic region. Finally, temporary and local in vivo suppression of PSD-95
      synthesis by using antisense oligodeoxynucleotides leads to inhibition of nNOS
      activity in the preoptic region and disrupted estrous cyclicity, a process
      requiring coordinated activation of neurons containing gonadotropin-releasing
      hormone (the neuropeptide controlling reproductive function). In conclusion, our
      findings identify a novel steroid-mediated molecular mechanism that enables the
      adult mammalian brain to control NO release under physiological conditions.

PMID- 17553984
TI  - Nuclear factor I coordinates multiple phases of cerebellar granule cell
      development via regulation of cell adhesion molecules.
AB  - A central question is how various stages of neuronal development are integrated
      as a differentiation program. Here we show that the nuclear factor I (NFI) family
      of transcriptional regulators is expressed and functions throughout the
      postmitotic development of cerebellar granule neurons (CGNs). Expression of an
      NFI dominant repressor in CGN cultures blocked axon outgrowth and dendrite
      formation and decreased CGN migration. Inhibition of NFI transactivation also
      disrupted extension and fasciculation of parallel fibers as well as CGN migration
      to the internal granule cell layer in cerebellar slices. In postnatal day 17 Nfia
      deficient mice, parallel fibers were greatly diminished and disoriented, CGN
      dendrite formation was dramatically impaired, and migration from the external
      germinal layer (EGL) was retarded. Axonal marker expression also was disrupted
      within the EGL of embryonic day 18 Nfib-null mice. NFI regulation of axon
      extension was observed under conditions of homotypic cell contact, implicating
      cell surface proteins as downstream mediators of its actions in CGNs. Consistent
      with this, the cell adhesion molecules ephrin B1 and N-cadherin were identified
      as NFI gene targets in CGNs using inhibitor and Nfi mutant analysis as well as
      chromatin immunoprecipitation. Functional inhibition of ephrin B1 or N-cadherin
      interfered with CGN axon extension and guidance, migration, and dendritogenesis
      in cell culture as well as in situ. These studies define NFI as a key regulator
      of postmitotic CGN development, in particular of axon formation, dendritogenesis,
      and migratory behavior. Furthermore, they reveal how a single transcription
      factor family can control and integrate multiple aspects of neuronal
      differentiation through the regulation of cell adhesion molecules.

PMID- 17553986
TI  - Where am I now? Distinct roles for parahippocampal and retrosplenial cortices in
      place recognition.
AB  - A key component of spatial navigation is the ability to use visual information to
      ascertain where one is located and how one is oriented in the world. We used
      functional magnetic resonance imaging to examine the neural correlates of this
      phenomenon in humans. Subjects were scanned while retrieving different kinds of
      topographical and nontopographical information in response to visual scenes. In
      the three critical conditions, they viewed images of a familiar college campus,
      and reported either the location of the place depicted in the image (location
      task), the compass direction that the camera was facing when the image was taken
      (orientation task), or whether the location was on campus or not (familiarity
      task). Our analyses focused on the retrosplenial cortex (RSC)/parietal-occipital
      sulcus region and the parahippocampal place area (PPA), which previous studies
      indicate play a critical role in place recognition. RSC activity depended on the
      type of information retrieved, with the strongest response in the location task.
      In contrast, PPA activity did not depend on the retrieval task. Additional
      analyses revealed a strong effect of familiarity in RSC but not in the PPA, with
      the former region responding much more strongly to images of the familiar campus
      than to images of an unfamiliar campus. These results suggest that the PPA and
      RSC play distinct but complementary roles in place recognition. In particular,
      the PPA may primarily support perception of the immediate scene, whereas RSC may
      support memory retrieval mechanisms that allow the scene to be localized within
      the broader spatial environment.

PMID- 17553985
TI  - Histone deacetylase inhibitors enhance memory and synaptic plasticity via
      CREB:CBP-dependent transcriptional activation.
AB  - Histone deacetylase (HDAC) inhibitors increase histone acetylation and enhance
      both memory and synaptic plasticity. The current model for the action of HDAC
      inhibitors assumes that they alter gene expression globally and thus affect
      memory processes in a nonspecific manner. Here, we show that the enhancement of
      hippocampus-dependent memory and hippocampal synaptic plasticity by HDAC
      inhibitors is mediated by the transcription factor cAMP response element-binding
      protein (CREB) and the recruitment of the transcriptional coactivator and histone
      acetyltransferase CREB-binding protein (CBP) via the CREB-binding domain of CBP.
      Furthermore, we show that the HDAC inhibitor trichostatin A does not globally
      alter gene expression but instead increases the expression of specific genes
      during memory consolidation. Our results suggest that HDAC inhibitors enhance
      memory processes by the activation of key genes regulated by the CREB:CBP
      transcriptional complex.

PMID- 17553987
TI  - UNC-31 (CAPS) is required for dense-core vesicle but not synaptic vesicle
      exocytosis in Caenorhabditis elegans.
AB  - Previous studies indicated that CAPS (calcium-dependent activator protein for
      secretion) functions as an essential component for the Ca2+-dependent exocytosis
      of dense-core vesicles in neuroendocrine cells. However, recent mouse knock-out
      studies suggested an alternative role in the vesicular uptake or storage of
      catecholamines. To genetically assess the functional role of CAPS, we
      characterized the sole Caenorhabditis elegans CAPS ortholog UNC-31 (uncoordinated
      family member) and determined its role in dense-core vesicle-mediated peptide
      secretion and in synaptic vesicle recycling. Novel assays for dense-core vesicle
      exocytosis were developed by expressing a prepro-atrial natriuretic factor-green
      fluorescent protein fusion protein in C. elegans. unc-31 mutants exhibited
      reduced peptide release in vivo and lacked evoked peptide release in cultured
      neurons. In contrast, cultured neurons from unc-31 mutants exhibited normal
      stimulated synaptic vesicle recycling measured by FM4-64 [N-(3
      triethylammoniumpropyl)-4-(6-(4-diethylamino)phenyl)hexatrienyl)pyridinium
      dibromide] dye uptake. Conversely, UNC-13, which exhibits sequence homology to
      CAPS/UNC-31, was found to be essential for synaptic vesicle but not dense-core
      vesicle exocytosis. These findings indicate that CAPS/UNC-31 function is not
      restricted to catecholaminergic vesicles but is generally required for and
      specific to dense-core vesicle exocytosis. Our results suggest that CAPS/UNC-31
      and UNC-13 serve parallel and dedicated roles in dense-core vesicle and synaptic
      vesicle exocytosis, respectively, in the C. elegans nervous system.

PMID- 17553988
TI  - A role for transcriptional repressor methyl-CpG-binding protein 2 and plasticity
      related gene serum- and glucocorticoid-inducible kinase 1 in the induction of
      inflammatory pain states.
AB  - Activity-dependent changes in neurons of the rat superficial dorsal horn are
      crucial for the induction and maintenance of neuropathic and inflammatory pain
      states. To identify the molecular mechanisms underlying this sensitization of
      superficial dorsal horn neurons, we undertook a genome-wide microarray profiling
      of dorsal horn gene transcripts at various times after induction of peripheral
      inflammation of the rat ankle joint. At early time points, upregulation of gene
      expression dominated, but by 7 d, downregulation was predominant. Two to 24 h
      after inflammation, we identified a small number of highly upregulated
      transcripts previously shown to be repressed by the Methyl-CpG-binding protein 2
      (MeCP2), including serum- and glucocorticoid-inducible kinase (SGK1) and FK 506
      binding protein 5, genes known to be important in experience-dependent
      plasticity. A decrease in expression of SIN3A, a corepressor in the MeCP2
      silencing complex, was also found after inflammation. Phosphorylation of MeCP2
      regulates activity-dependent gene transcription, and crucially we found that
      MeCP2 was phosphorylated in lamina I projection neurons 1 h after induction of
      peripheral inflammation. Lamina I projection neurons have been shown to be
      essential for the development of most pain states. SGK1 protein was also
      localized, in part, to lamina I projection neurons, and its expression in the
      superficial dorsal horn increased after inflammation. Furthermore, antisense
      knock-down of SGK1 delayed the onset of inflammatory hyperalgesia by 24 h at
      least. Our results uncover an unexpected complexity in the regulation of gene
      expression, including the modulation of transcriptional repression, that
      accompanies development and maintenance of an inflammatory pain state.

PMID- 17553990
TI  - A crucial role for p57(Kip2) in the intracellular timer that controls
      oligodendrocyte differentiation.
AB  - The intracellular molecular mechanism that controls the timing of oligodendrocyte
      differentiation remains unknown. Temple and Raff (1986) previously showed that an
      oligodendrocyte precursor cell (OPC) can divide a maximum of approximately eight
      times before its daughter cells simultaneously cease proliferating and
      differentiate into oligodendrocytes. They postulated that over time the level of
      an intracellular molecule might synchronously change in each daughter cell,
      ultimately reaching a level that prohibited additional proliferation. Here, we
      report the discovery of such a molecule, the cyclin-dependent kinase inhibitor
      p57(Kip2) (Cdkn1c). We show in vitro that all daughters of a clone of OPCs
      express similar levels of p57(Kip2), that p57(Kip2) levels increase over time in
      proliferating OPCs, and that p57(Kip2) levels regulate how many times an OPC can
      divide before differentiating. These findings reveal a novel part of the
      mechanism by which OPCs measure time and are likely to extend to similar timers
      in many other precursor cell types.

PMID- 17553989
TI  - Amyloid deposition begins in the striatum of presenilin-1 mutation carriers from
      two unrelated pedigrees.
AB  - The amyloid cascade hypothesis suggests that the aggregation and deposition of
      amyloid-beta protein is an initiating event in Alzheimer's disease (AD). Using
      amyloid imaging technology, such as the positron emission tomography (PET) agent
      Pittsburgh compound-B (PiB), it is possible to explore the natural history of
      preclinical amyloid deposition in people at high risk for AD. With this goal in
      mind, asymptomatic (n = 5) and symptomatic (n = 5) carriers of presenilin-1 (PS1)
      mutations (C410Y or A426P) that lead to early-onset AD and noncarrier controls
      from both kindreds (n = 2) were studied with PiB-PET imaging and compared with
      sporadic AD subjects (n = 12) and controls from the general population (n = 18).
      We found intense and focal PiB retention in the striatum of all 10 PS1 mutation
      carriers studied (ages 35-49 years). In most PS1 mutation carriers, there also
      were increases in PiB retention compared with controls in cortical brain areas,
      but these increases were not as great as those observed in sporadic AD subjects.
      The two PS1 mutation carriers with a clinical diagnosis of early-onset AD did not
      show the typical regional pattern of PiB retention observed in sporadic AD.
      Postmortem evaluation of tissue from two parents of PS1C410Y subjects in this
      study confirmed extensive striatal amyloid deposition, along with typical
      cortical deposition. The early, focal striatal amyloid deposition observed in
      these PS1 mutation carriers is often is not associated with clinical symptoms.

PMID- 17553991
TI  - The relation of brain oscillations to attentional networks.
AB  - Previous studies have suggested the relation of particular frequency bands such
      as theta (4-8 Hz), alpha (8-14 Hz), beta (14-30 Hz), or gamma (>30 Hz) to
      cognitive functions. However, there has been controversy over which bands are
      specifically related to attention. We used the attention network test to separate
      three anatomically defined brain networks that carry out the functions of
      alerting, orienting, and executive control of attention. High-density scalp
      electrical recording was performed to record synchronous oscillatory activity and
      power spectrum analyses based on functional magnetic resonance imaging
      constrained dipole modeling were conducted for each attentional network. We found
      that each attentional network has a distinct set of oscillations related to its
      activity. The alerting network showed a specific decrease in theta-, alpha-, and
      beta-band activity 200-450 ms after a warning signal. The orienting network
      showed an increase in gamma-band activity at approximately 200 ms after a spatial
      cue, indicating the location of a target. The executive control network revealed
      a complex pattern when a target was surrounded with incongruent flankers compared
      with congruent flankers. There was an early (<400 ms) increase in gamma-band
      activity, a later (>400 ms) decrease in beta- and low gamma-band activity after
      the target onset, and a decrease of all frequency bands before response followed
      by an increase after the response. These data demonstrate that attention is not
      related to any single frequency band but that each network has a distinct
      oscillatory activity and time course.

PMID- 17553992
TI  - Deletion of apolipoprotein E receptor-2 in mice lowers brain selenium and causes
      severe neurological dysfunction and death when a low-selenium diet is fed.
AB  - Selenoprotein P (Sepp1) is a plasma and extracellular protein that is rich in
      selenium. Deletion of Sepp1 results in sharp decreases of selenium levels in the
      brain and testis with dysfunction of those organs. Deletion of Sepp1 also causes
      increased urinary selenium excretion, leading to moderate depletion of whole-body
      selenium. The lipoprotein receptor apolipoprotein E receptor-2 (apoER2) binds
      Sepp1 and facilitates its uptake by Sertoli cells, thus providing selenium for
      spermatogenesis. Experiments were performed to assess the effect of apoER2 on the
      concentration and function of selenium in the brain and on whole-body selenium.
      ApoER2-/- and apoER2+/+ male mice were fed a semipurified diet with selenite
      added as the source of selenium. ApoER2-/- mice had depressed brain and testis
      selenium, but normal levels in liver, kidney, muscle, and the whole body. Feeding
      a selenium-deficient diet to apoER2-/- mice led to neurological dysfunction and
      death, with some of the characteristics exhibited by Sepp1-/- mice fed the same
      diet. Thus, although it does not affect whole-body selenium, apoER2 is necessary
      for maintenance of brain selenium and for prevention of neurological dysfunction
      and death under conditions of selenium deficiency, suggesting an interaction of
      apoER2 with Sepp1 in the brain.

PMID- 17553993
TI  - Activation of prefrontal cortex by transcranial direct current stimulation
      reduces appetite for risk during ambiguous decision making.
AB  - As adult humans, we are continuously faced with decisions in which proper
      weighing of the risk involved is critical. Excessively risky or overly cautious
      decision making can both have disastrous real-world consequences. Weighing of
      risks and benefits toward decision making involves a complex neural network that
      includes the dorsolateral prefrontal cortex (DLPFC), but its role remains
      unclear. Repetitive transcranial magnetic stimulation studies have shown that
      disruption of the DLPFC increases risk-taking behavior. Transcranial direct
      current stimulation (tDCS) allows upregulation of activity in the DLPFC, and we
      predicted that it might promote more cautious decision making. Healthy
      participants received one of the following treatments while they performed the
      Balloon Analog Risk Task: (1) right anodal/left cathodal DLPFC tDCS, (2) left
      anodal/right cathodal DLPFC tDCS, or (3) sham tDCS. This experiment revealed that
      participants receiving either one of the bilateral DLPFC tDCS strategies adopted
      a risk-averse response style. In a control experiment, we tested whether
      unilateral DLPFC stimulation (anodal tDCS over the right or left DLPFC with the
      cathodal electrode over the contralateral supraorbital area) was sufficient to
      decrease risk-taking behaviors. This experiment showed no difference in decision
      making behaviors between the groups of unilateral DLPFC stimulation and sham
      stimulation. These findings extend the notion that DLPFC activity is critical for
      adaptive decision making, possibly by suppressing riskier responses. Anodal tDCS
      over DLPFC by itself did not significantly change risk-taking behaviors; however,
      when the contralateral DLPFC was modulated with cathodal tCDS, an important
      decrease in risk taking was observed. Also, the induced cautious decision-making
      behavior was observed only when activity of both DLPFCs was modulated. The
      ability to modify risk-taking behavior may be translated into therapeutic
      interventions for disorders such as drug abuse, overeating, or pathological
      gambling.

PMID- 17553994
TI  - Selective tuning of the blood oxygenation level-dependent response during simple
      target detection dissociates human frontoparietal subregions.
AB  - Current models of working memory and focal attention converge on the idea of an
      adaptable global system, distributed across a network of frontal and parietal
      brain regions. Here, we examine how the human frontoparietal network selectively
      adapts to represent currently relevant information during a simple attentional
      task: monitoring for a target item in a series of nontargets. Across the entire
      frontoparietal network, there is selective response to targets, in line with a
      global system for coding task-relevant inputs. At the same time, there are
      striking dissociations in response to nontargets; whereas ventrolateral frontal
      cortex responds just to the target, more dorsal/anterior regions respond to all
      stimuli from the target category. The results show different degrees of target
      selectivity across different regions of the frontoparietal network.

PMID- 17553995
TI  - Dendritic pathology in prion disease starts at the synaptic spine.
AB  - Spine loss represents a common hallmark of neurodegenerative diseases. However,
      little is known about the underlying mechanisms, especially the relationship
      between spine elimination and neuritic destruction. We imaged cortical dendrites
      throughout a neurodegenerative disease using scrapie in mice as a model. Two
      photon in vivo imaging over 2 months revealed a linear decrease of spine density.
      Interestingly, only persistent spines (lifetime > or = 8 d) disappeared, whereas
      the density of transient spines (lifetime < or = 4 d) was unaffected. Before
      spine loss, dendritic varicosities emerged preferentially at sites where spines
      protrude from the dendrite. These results implicate that the location where the
      spine protrudes from the dendrite may be particularly vulnerable and that
      dendritic varicosities may actually cause spine loss.

PMID- 17553996
TI  - Enhanced category tuning revealed by intracranial electroencephalograms in high
      order human visual areas.
AB  - The functional organization of human sensory cortex was studied by comparing
      intracranial EEG (iEEG) recordings of local field potentials in neurosurgical
      patients with functional magnetic resonance imaging (fMRI) obtained in healthy
      subjects. Using naturalistic movie stimuli, we found a tight correlation between
      these two measures throughout the human sensory cortex. Importantly, the
      correlation between the iEEG and fMRI signals was site-specific, exhibiting
      neuroanatomically specific coupling. In several cortical sites the iEEG activity
      was confined strictly to one object category. This site selectivity was not
      limited to faces but included other object categories such as houses and tools.
      The selectivity of the iEEG signals to images of different object categories was
      remarkably higher when compared with the selectivity of the corresponding fMRI
      signals. A plausible interpretation of the fMRI and iEEG results concerns
      cortical organization in which object categories are organized in a mosaic of
      narrowly tuned object-selective clusters.

PMID- 17553997
TI  - Protein kinase CK2 impairs spatial memory formation through differential cross
      talk with PI-3 kinase signaling: activation of Akt and inactivation of SGK1.
AB  - Casein kinase II (CK2) is a multifunctional serine/threonine protein kinase that
      is associated with the development of neuritogenesis and synaptic plasticity. The
      phosphoinositide 3-kinase (PI-3K)/Akt pathway is implicated in long-term memory
      formation. In addition, serum- and glucocorticoid-inducible kinase 1 (SGK1) is
      another downstream target of PI-3K signaling that was shown to play an important
      role in spatial memory formation. Whether CK2 may also affect memory formation
      and whether CK2 interacts with Akt and SGK1 during this process is unknown. In
      the present study, we found that water maze training significantly decreased CK2
      activity in the rat hippocampal CA1 area but not in the dentate gyrus (DG) area.
      Transfection of the dominant negative mutant of CK2, CK2alphaA(156), to the CA1
      area, but not to the DG area, decreased CK2 activity but enhanced spatial memory
      formation. Meanwhile, it increased SGK1 phosphorylation at Ser422, decreased Akt
      phosphorylation at Ser473, and increased cAMP response element-binding protein
      phosphorylation at Ser133. Transfection of the constitutively active SGK1,
      SGKS422D, enhanced whereas transfection of the wild-type Akt impaired spatial
      memory formation. Also, administration of the protein phosphatase 2A inhibitor,
      fostriecin, reversed the memory-impairing effect of CK2alphaWT. It also reversed
      the effect of CK2alphaWT in decreasing SGK1 phosphorylation. Akt Ser473
      phosphorylation was moderately increased by CK2alphaWT and fostriecin treatment,
      but AktS473A mutant transfection reversed the memory-impairing effect of
      CK2alphaWT. These results together suggest that CK2 impairs spatial memory
      formation through differential cross talk with PI-3 kinase signaling by
      activation of Akt and inactivation of SGK1 through protein phosphatase 2A.

PMID- 17553998
TI  - Localization and expression of group I metabotropic glutamate receptors in the
      mouse striatum, globus pallidus, and subthalamic nucleus: regulatory effects of
      MPTP treatment and constitutive Homer deletion.
AB  - Group I metabotropic glutamate receptors (mGluRs), mGluR1 and mGluR5, regulate
      activity in the globus pallidus (GP) and subthalamic nucleus (STN). To test
      whether the localization of group I mGluRs is altered in parkinsonism, we used
      immunoelectron microscopy to analyze the subcellular and subsynaptic distribution
      of mGluR1a and mGluR5 in GP and STN of 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine (MPTP)-treated mice. Homer1 and Homer2 knock-out mice were
      used to assess the role of Homer in MPTP-induced redistribution of group I
      mGluRs. We also examined the effects of MPTP on the expression levels of group I
      mGluRs and Homer proteins in GP and striatum. MPTP treatment significantly
      reduced the expression levels of H1a and mGluR1a in striatum but not in GP.
      Although light microscopy did not reveal noticeable effects of MPTP treatment on
      the distribution of group I mGluRs and Homer proteins in GP and STN, specific
      changes in the ultrastructural localization of mGluR1a were found in MPTP-treated
      normal and Homer knock-out mice. An increase in the expression of presynaptic
      axonal and terminal mGluR1a labeling and an increased level of mGluR1a
      immunoreactivity in the postsynaptic specialization of putative GABAergic
      synapses were among the most significant effects induced by dopamine depletion.
      However, neither of these changes was found for mGluR5, which, in contrast,
      displayed complex regulatory alterations in its subsynaptic distribution in
      response to Homer deletion and MPTP lesion. Thus, nigrostriatal dopaminergic
      lesion and Homer deletion lead to changes in the trafficking of group I mGluRs in
      vivo that are specific to receptor subtypes and brain areas.

PMID- 17553999
TI  - A novel connection between rods and ON cone bipolar cells revealed by ectopic
      metabotropic glutamate receptor 7 (mGluR7) in mGluR6-deficient mouse retinas.
AB  - Since the discovery of direct chemical synapses between rod photoreceptor and OFF
      cone bipolar cells in mouse retinas, whether the ON cone bipolar cell also
      receive direct chemical input from rod has been a pending question. In finding
      that metabotropic glutamate receptor 7 (mGluR7) was uniquely expressed in
      dendrites of ON cone bipolar cells in the mGluR6-deficient mouse retina, we used
      this ectopic mGluR7 immunoreactivity as a specific marker for the ON cone bipolar
      to search for its rod connection. Here, we show that a certain type of ON cone
      bipolar cell forms ribbon-associated synapses not only with cones, but also rods.
      This finding was verified in the wild-type mouse retina by three-dimensional
      reconstruction of bipolar cells from serial electron micrographs. These ON cone
      bipolars were further identified as corresponding to type 7 of mouse bipolar cell
      described by Ghosh et al. (2004) and also to the green fluorescent protein (GFP)
      labeled type 7 bipolars in the alpha-gustducin-GFP transgenic mouse. Our findings
      suggest that, in mice, rod signals bifurcate into a third ON and OFF pathway in
      addition to the two known routes to cone bipolar cells: (1) via rod chemical
      synapse --> rod bipolar --> AII amacrine --> ON and OFF cone bipolar cells; (2)
      via rod-cone gap junction --> cone chemical synapse --> ON and OFF cone bipolar
      cells; and (3) via rod chemical synapse --> ON and OFF cone bipolar cells. This
      third novel pathway is thought to transmit fast and moderately light-sensitive
      rod signals, functioning to smooth out the intensity changes at the scotopic
      mesopic interface.

PMID- 17554000
TI  - Rapid astrocyte calcium signals correlate with neuronal activity and onset of the
      hemodynamic response in vivo.
AB  - Elevation of intracellular Ca2+ in astrocytes can influence cerebral
      microcirculation and modulate synaptic transmission. Recently, in vivo imaging
      studies identified delayed, sensory-driven Ca2+ oscillations in cortical
      astrocytes; however, the long latencies of these Ca2+ signals raises questions in
      regards to their suitability for a role in short-latency modulation of cerebral
      microcirculation or rapid astrocyte-to-neuron communication. Here, using in vivo
      two-photon Ca2+ imaging, we demonstrate that approximately 5% of sulforhodamine
      101-labeled astrocytes in the hindlimb area of the mouse primary somatosensory
      cortex exhibit short-latency (peak amplitude approximately 0.5 s after stimulus
      onset), contralateral hindlimb-selective sensory-evoked Ca2+ signals that operate
      on a time scale similar to neuronal activity and correlate with the onset of the
      hemodynamic response as measured by intrinsic signal imaging. The kinetics of
      astrocyte Ca2+ transients were similar in rise and decay times to postsynaptic
      neuronal transients, but decayed more slowly than neuropil Ca2+ transients that
      presumably reflect presynaptic transients. These in vivo findings suggest that
      astrocytes can respond to sensory activity in a selective manner and process
      information on a subsecond time scale, enabling them to potentially form an
      active partnership with neurons for rapid regulation of microvascular tone and
      neuron-astrocyte network properties.

PMID- 17554001
TI  - The transporters GlyT2 and VIAAT cooperate to determine the vesicular glycinergic
      phenotype.
AB  - The mechanisms that specify the vesicular phenotype of inhibitory interneurons in
      vertebrates are poorly understood because the two main inhibitory transmitters,
      glycine and GABA, share the same vesicular inhibitory amino acid transporter
      (VIAAT) and are both present in neurons during postnatal development. We have
      expressed VIAAT and the plasmalemmal transporters for glycine and GABA in a
      neuroendocrine cell line and measured the quantal release of glycine and GABA
      using a novel double-sniffer patch-clamp technique. We found that glycine is
      released from vesicles when VIAAT is coexpressed with either the neuronal
      transporter GlyT2 or the glial transporter GlyT1. However, GlyT2 was more
      effective than GlyT1, probably because GlyT2 is unable to operate in the reverse
      mode, which gives it an advantage in maintaining the high cytosolic glycine
      concentration required for efficient vesicular loading by VIAAT. The vesicular
      inhibitory phenotype was gradually altered from glycinergic to GABAergic through
      mixed events when GABA is introduced into the secretory cell and competes for
      uptake by VIAAT. Interestingly, the VIAAT ortholog from Caenorhabditis elegans
      (UNC-47), a species lacking glycine transmission, also supports glycine
      exocytosis in the presence of GlyT2, and a point mutation of UNC-47 that
      abolishes GABA transmission in the worm confers glycine specificity. Together,
      these results suggest that an increased cytosolic availability of glycine in
      VIAAT-containing terminals was crucial for the emergence of glycinergic
      transmission in vertebrates.

PMID- 17554002
TI  - Anatomical correlates of sentence comprehension and verbal working memory in
      neurodegenerative disease.
AB  - This study investigates whether sentence comprehension and nonsyntactic verbal
      working memory (vWM) are sustained by the same or by different neural systems.
      Scores in a sentence-picture matching task and in digits backward (DB) were
      correlated with magnetic resonance imaging voxelwise gray matter volumes using
      voxel-based morphometry in 58 patients with neurodegenerative diseases. Results
      showed that overall sentence comprehension scores, regardless of grammatical
      structure, correlated with gray matter volumes in the left temporoparietal
      region, whereas DB scores correlated with dorsolateral prefrontal and inferior
      parietal volumes. Comprehension of multiclausal relative sentences (type 3)
      significantly correlated with voxels in the dorsal portion of the left inferior
      and middle frontal gyri. When DB and multiclausal relative sentences were
      directly compared, they showed overlapping neural substrates in the dorsolateral
      left frontal region, supporting a single source of vWM for syntactic and
      nonsyntactic tasks. Within this large area of common involvement, a small portion
      of pars triangularis showed an independent effect of multiclausal sentences,
      whereas a region in the middle frontal gyrus showed greater correlation with DB.
      This study reconciles two opposing views, which hold that sentence comprehension
      and vWM rely on either the same or different anatomical resources.

PMID- 17554003
TI  - Dissociating timing and coordination as functions of the cerebellum.
AB  - The function of the cerebellum in motor control is a long-standing puzzle because
      cerebellar damage is associated with both timing and coordination deficits.
      Timing is the ability to produce consistent intervals between movements based on
      an internal representation of time. Coordination, in contrast, is a state
      dependent control process in which motor commands to one effector depend on the
      predicted state of another effector. Here we considered a task consisting of two
      components, an arm movement and an isometric press with the thumb. We found that
      when the two components temporally overlapped, the brain controlled the thumb
      using an estimate of the state of the arm. In contrast, when the components did
      not temporally overlap, the brain controlled the thumb solely based on an
      internal estimate of time. Using functional magnetic resonance imaging, we
      contrasted these two conditions and found that lobule V of the cerebellum
      ipsilateral to the arm movement was consistently more activated during state
      dependent control. When the brain learned time-dependent control, no region of
      the cerebellum showed consistently increased activity compared with state
      dependent control. Rather, the consistent activity associated with time-dependent
      control was found in language areas of the left cerebral hemisphere along the
      Sylvian fissure. We suggest that timing and coordination are behaviorally
      distinct modes of motor control and that the anterior cerebellum is a crucial
      node in state-dependent motor control, computing a predictive state estimate of
      one effector (e.g., the arm) to coordinate actions of another effector (the
      thumb).

PMID- 17554004
TI  - Inhibition of resting potassium conductances by long-term activation of the
      NO/cGMP/protein kinase G pathway: a new mechanism regulating neuronal
      excitability.
AB  - Glutamate-induced excitotoxicity, the most common pathological mechanism leading
      to neuronal death, may occur even with normal levels of glutamate if it coincides
      with a persistent enhancement of neuronal excitability. Neurons expressing nitric
      oxide (NO) synthase (NOS-I), which is upregulated in many human chronic
      neurodegenerative diseases, are highly susceptible to neurodegeneration. We
      hypothesized that chronic production of NO in damaged neurons may increase their
      intrinsic excitability via modulation of resting or "leak" K+ currents.
      Peripheral XIIth nerve injury in adult rats induced de novo NOS-I expression and
      an increased incidence of low-threshold motor units, the latter being prevented
      by chronic inhibition of the neuronal NO/cGMP pathway. Accordingly, sustained
      synthesis of NO maintained an enhanced basal activity in injured motoneurons that
      was slowly reverted (over the course of 2-3 h) by NOS-I inhibitors. In slice
      preparations, persistent, but not acute, activation of the NO/cGMP pathway evoked
      a robust augment in motoneuron excitability independent of synaptic activity.
      Furthermore, chronic activation of the NO/cGMP pathway fully suppressed TWIK
      related acid-sensitive K+ (TASK) currents through a protein kinase G (PKG)
      dependent mechanism. Finally, we found evidence for the involvement of this long
      term mechanism in regulating membrane excitability of motoneurons, because their
      pH-sensitive currents were drastically reduced by nerve injury. This NO/cGMP/PKG
      mediated modulation of TASK conductances might represent a new pathological
      mechanism that leads to hyperexcitability and sensitizes neurons to excitotoxic
      damage. It could explain why de novo expression of NOS-I and/or its
      overexpression makes them susceptible to neurodegeneration under pathological
      conditions.

PMID- 17554005
TI  - Cerebral blood flow in immediate and sustained anxiety.
AB  - The goal of this study was to compare cerebral blood flow (CBF) changes
      associated with phasic cued fear versus those associated with sustained
      contextual anxiety. Positron emission tomography images of CBF were acquired
      using [O-15]H2O in 17 healthy human subjects as they anticipated unpleasant
      electric shocks that were administered predictably (signaled by a visual cue) or
      unpredictably (threatened by the context). Presentation of the cue in either
      threat condition was associated with increased CBF in the left amygdala. A cue
      that specifically predicted the shock was associated with CBF increases in the
      ventral prefrontal cortex (PFC), hypothalamus, anterior cingulate cortex, left
      insula, and bilateral putamen. The sustained threat context increased CBF in the
      right hippocampus, mid-cingulate gyrus, subgenual PFC, midbrain periaqueductal
      gray, thalamus, bilateral ventral striatum, and parieto-occipital cortex. This
      study showed distinct neuronal networks involved in cued fear and contextual
      anxiety underlying the importance of this distinction for studies on the
      pathophysiology of anxiety disorders.

PMID- 17554006
TI  - Neuron-specific inactivation of the hypoxia inducible factor 1 alpha increases
      brain injury in a mouse model of transient focal cerebral ischemia.
AB  - In the present study, we show a biphasic activation of hypoxia inducible factor
      1alpha (HIF-1) after stroke that lasts for up to 10 d, suggesting the involvement
      of the HIF pathway in several aspects of the pathophysiology of cerebral
      ischemia. We provide evidence that HIF-1-mediated responses have an overall
      beneficial role in the ischemic brain as indicated by increased tissue damage and
      reduced survival rate of mice with neuron-specific knockdown of HIF-1alpha that
      were subjected to transient focal cerebral ischemia. In addition, we demonstrated
      that drugs known to activate HIF-1 in cultured cells as well as in vivo had
      neuroprotective properties in this model of cerebral ischemia. This protective
      effect was significantly attenuated but not completely abolished in neuron
      specific HIF-1alpha-deficient mice, suggesting that alternative mechanisms of
      neuroprotection are also implicated. Last, our study showed that hypoxia-induced
      tolerance to ischemia was preserved in neuron-specific HIF-1alpha-deficient mice,
      indicating that the neuroprotective effects of hypoxic preconditioning do not
      depend on neuronal HIF-1 activation.

PMID- 17554007
TI  - Plexin-B2, but not Plexin-B1, critically modulates neuronal migration and
      patterning of the developing nervous system in vivo.
AB  - Semaphorins and their receptors, plexins, have emerged as important cellular cues
      regulating key developmental processes. B-type plexins directly regulate the
      actin cytoskeleton in a variety of cell types. Recently, B-type plexins have been
      shown to be expressed in striking patterns in the nervous system over critical
      developmental windows. However, in contrast to the well characterized plexin-A
      family, the functional role of plexin-B proteins in neural development and
      organogenesis in vertebrates in vivo is not known. Here, we have elucidated the
      functional contribution of the two neuronally expressed plexin-B proteins, Plexin
      B1 or Plexin-B2, toward the development of the peripheral nervous system and the
      CNS by generating and analyzing constitutive knock-out mice. The development of
      the nervous system was found to be normal in mice lacking Plexin-B1, whereas mice
      lacking Plexin-B2 demonstrated defects in closure of the neural tube and a
      conspicuous disorganization of the embryonic brain. After analyzing mutant mice,
      which bypassed neural tube defects, we observed a key requirement for Plexin-B2
      in proliferation and migration of granule cell precursors in the developing
      dentate gyrus, olfactory bulb, and cerebellum. Furthermore, we identified
      semaphorin 4C as a high-affinity ligand for Plexin-B2 in binding and functional
      assays. Semaphorin 4C stimulated activation of ErbB-2 and RhoA via Plexin-B2 and
      enhanced proliferation and migration of granule cell precursors. Semaphorin 4C
      induced proliferation of ventricular zone neuroblasts was abrogated in mice
      lacking Plexin-B2. These genetic and functional analyses reveal a key requirement
      for Plexin-B2, but not Plexin-B1, in patterning of the vertebrate nervous system
      in vivo.

PMID- 17554008
TI  - Free fluid in Morison's pouch on bedside ultrasound predicts need for operative
      intervention in suspected ectopic pregnancy.
AB  - BACKGROUND: Ectopic pregnancies are frequently present in women who present to
      the emergency department with pregnancy and abdominal pain or bleeding, a subset
      of whom may require operative intervention. OBJECTIVES: To prospectively
      determine if emergency physician (EP)-performed transabdominal pelvic
      ultrasonography (US) with determination of free abdominal fluid in the
      hepatorenal space predicted the need for operative intervention. METHODS:
      Patients who were suspected to have an ectopic pregnancy were prospectively
      enrolled over a ten-month period. An EP-performed bedside transabdominal pelvic
      US that included a view of the hepatorenal space (Morison's pouch) for free
      fluid. The EP US was classified as intrauterine pregnancy (IUP) or no definitive
      IUP, with Morison's pouch classified as positive or negative. The majority of
      patients had a subsequent transvaginal pelvic US performed by the Department of
      Radiology. Patients were followed up for radiology results, need for operative
      intervention, and ultimate outcome of the pregnancy. RESULTS: There were 242
      patients enrolled, with an average time to complete the EP US of 4 minutes and 27
      seconds. There were 28 ectopic pregnancies diagnosed (11.6%), of which 18
      patients underwent operative intervention. Free fluid in Morison's pouch was
      identified in ten patients, nine of whom underwent operative intervention,
      yielding a positive likelihood ratio of 112 (95% confidence interval = 15 to 831)
      for patients with suspected ectopic pregnancy who required operative
      intervention. CONCLUSIONS: Free intraperitoneal fluid found in Morison's pouch in
      patients with suspected ectopic pregnancy may be rapidly identified at the
      bedside by EP-performed US and predicts the need for operative intervention.

PMID- 17554009
TI  - Lack of agreement in pediatric emergency department discharge diagnoses from
      clinical and administrative data sources.
AB  - BACKGROUND: Diagnosis information from existing data sources is used commonly for
      epidemiologic, administrative, and research purposes. The quality of such data
      for emergency department (ED) visits is unknown. OBJECTIVES: To determine the
      agreement on final diagnoses between two sources, electronic administrative
      sources and manually abstracted medical records, for pediatric ED visits, in a
      multicenter network. METHODS: This was a cross sectional study at 19 EDs
      nationwide. The authors obtained data from two sources at each ED during a three
      month period in 2003: administrative sources for all visits and abstracted
      records for randomly selected visits during ten days over the study period.
      Records were matched using unique identifiers and probabilistic linkage. The
      authors recorded up to three diagnoses from each abstracted medical record and up
      to ten for the administrative data source. Diagnoses were grouped into 104 groups
      using a modification of the Clinical Classification System. RESULTS: A total of
      8,860 abstracted records had at least one valid diagnosis code (with a total of
      12,895 diagnoses) and were successfully matched to records in the administrative
      source. Overall, 67% (95% confidence interval = 66% to 68%) of diagnoses from the
      administrative and abstracted sources were within the same diagnosis group.
      Agreement varied by site, ranging from 54% to 77%. Agreement varied substantially
      by diagnosis group; there was no difference by method of linkage. Clustering
      clinically similar diagnosis groups improved agreement between administrative and
      abstracted data sources. CONCLUSIONS: ED diagnoses retrieved from electronic
      administrative sources and manual chart review frequently disagree, even if
      similar diagnosis codes are grouped. Agreement varies by institution and by
      diagnosis. Further work is needed to improve the accuracy of diagnosis coding;
      development of a grouping system specific to pediatric emergency care may be
      beneficial.

PMID- 17554010
TI  - Identifying injection drug users at risk of nonfatal overdose.
AB  - OBJECTIVES: Drug overdose is the second leading cause of accidental deaths among
      U.S. adults aged 15-64 years. Emergency physicians have a unique opportunity to
      provide overdose prevention interventions, because habitual drug users are in
      frequent need of medical care. The authors evaluated associations between
      individual-level risk factors and experiencing an overdose in the past six months
      to determine which characteristics and behaviors may be most predictive of
      overdose. METHODS: The authors used data from a sample of street-recruited
      habitual drug users who participated in face-to-face interviews about overdose
      from November 2001 to February 2004. This analysis was restricted to 772
      respondents who had been injecting for at least one year and who had injected
      heroin within the past two months. RESULTS: A total of 16.6% of participants had
      overdosed in the past six months. Characteristics and behaviors that were
      independently associated with an increased risk of a recent overdose were having
      had a prior overdose (odds ratio [OR], 28.58; 95% confidence interval [CI] =
      14.10 to 57.96), using cocaine/crack in the past six months (OR, 2.07; 95% CI =
      1.25 to 3.45), using alcohol in the past six months (OR, 1.90; 95% CI = 1.01 to
      3.57), experiencing serious withdrawal symptoms in the past two months (OR, 2.70;
      95% CI = 1.58 to 4.61), and younger age. CONCLUSIONS: Drug users who have
      previously experienced a nonfatal overdose are at very high risk of experiencing
      future overdoses. Further longitudinal studies are needed to identify robust
      predictors of overdose risk over time in habitual drug users, but these data
      suggest that drug users who have overdosed warrant aggressive prevention efforts
      such as agonist maintenance treatment or provision of take-home naloxone.

PMID- 17554011
TI  - Prospective study of the clinical features and outcomes of emergency department
      patients with delayed diagnosis of pulmonary embolism.
AB  - OBJECTIVES: The authors hypothesized that emergency department (ED) patients with
      a delayed diagnosis of pulmonary embolism (PE) will have a higher frequency of
      altered mental status, older age, comorbidity, and worsened outcomes compared
      with patients who have PE diagnosed by tests ordered in the ED. METHODS: For 144
      weeks, all patients with PE diagnosed by computed tomographic angiography were
      prospectively screened to identify ED diagnosis (testing ordered from the ED)
      versus delayed diagnosis (less than 48 hours postadmission). Serum troponin I
      level, right ventricular hypokinesis on echocardiography, and percentage
      pulmonary vascular occlusion were measured at diagnosis; patients were
      prospectively followed up for adverse events (death, intubation, or circulatory
      shock). RESULTS: Among 161 patients with PE, 141 (88%) were ED diagnosed and 20
      (12%) had a delayed diagnosis. Patients with a delayed diagnosis were older than
      ED-diagnosed patients (61 [+/-15] vs. 51 [+/-17] years; p < 0.001), had a longer
      median time to heparin administration (33 vs. 8 hours; p < 0.001), and had a
      higher frequency of altered mental status (30% vs. 8%; p = 0.01) but did not have
      a higher frequency of prior cardiopulmonary disease (25% vs. 23%). Patients with
      a delayed diagnosis had equal or worse measures of PE severity (right ventricular
      hypokinesis on echocardiography, 60% vs. 58%; abnormal troponin I level, 55% vs.
      24%); on computed tomographic angiography, ten of 20 patients with a delayed
      diagnosis had PE in lobar or larger arteries and >50% vascular obstruction.
      Patients with a delayed diagnosis had a higher rate of in-hospital adverse events
      (9% vs. 30%; p = 0.01). CONCLUSIONS: In this single-center study, the diagnosis
      of PE was frequently delayed and outcomes of patients with delayed diagnosis were
      worse than those of patients with PE diagnosed in the ED.

PMID- 17554012
TI  - We want the same thing: projection in judgments of sexual intent.
AB  - This article details two studies investigating the proximal role of social
      projection (i.e., assumed similarity) in judgments of sexual intent. Study 1
      demonstrates that men and women who have a greater desire for casual sex are more
      likely to perceive sexual intent in others. Study 2 replicates this finding in a
      more realistic context and, further, situates judgments of sexual intent squarely
      into the cognitive domain, as results show that projection of casual sexual
      motivation is more likely when the target is similar to the perceiver and when
      the target's motivation is relatively ambiguous to begin with.

PMID- 17554013
TI  - The perception of time heals all wounds: temporal distance affects willingness to
      forgive following an interpersonal transgression.
AB  - Prior research has assessed the temporal unfolding of forgiveness and found that
      forgiveness becomes more likely as time distances the victim from the
      transgression. These findings lend credence to the axiom "time heals all wounds."
      This research examines the effect of time perception on forgiveness of others by
      experimentally manipulating temporal distance. In Experiment 1, respondents
      reported greater willingness to forgive the transgressor when more time had
      elapsed since the transgression. Experiments 2 and 3 determined the influence of
      subjective temporal distance on willingness to forgive. Participants who
      perceived a hypothetical (Experiment 2) or real (Experimental 3) transgression to
      be farther away in time were more willing to forgive the target than were
      participants who perceived the event to be temporally closer. Results suggest
      that temporal appraisals of an event are central to the forgiveness process.

PMID- 17554014
TI  - IL-21 promotes T lymphocyte survival by activating the phosphatidylinositol-3
      kinase signaling cascade.
AB  - IL-21 is a Type I cytokine, which uses the common gamma chain (gamma(c)) in its
      receptor. As members of the gamma(c) cytokine/cytokine receptors family play
      crucial role in the differentiation, activation, and survival of lymphocytes, we
      have investigated if IL-21 could promote T cell survival and thus, contribute to
      T cell homeostasis and expansion. Unlike most gamma(c) cytokine receptors, we
      report that IL-21R is constitutively expressed by all mature T lymphocytes and
      that stromal cells of lymphoid organs are a constitutive source of IL-21. These
      observations are reminiscent of what is observed for IL-7/IL-7R, which control T
      cell survival and homeostasis and suggest a role for IL-21 in T cell homeostasis.
      Indeed, our results show that IL-21 is a survival factor for resting and
      activated T cells. Moreover, the ability of IL-21 to costimulate T cell
      proliferation is mediated by enhancing T cell viability. Further investigation of
      how IL-21R signaling induces T cell survival shows for the first time that IL-21
      binding to its receptor activates the PI-3K signaling pathway and induces Bcl-2
      expression. Moreover, the activation of the PI-3K signaling pathway is essential
      for IL-21-mediated T cell survival. Our data provide a new role for IL-21 in the
      immune system, which might be used to improve T cell homeostasis in
      immunocompromised patients.

PMID- 17554015
TI  - Polymorphonuclear leukocyte transverse migration induces rapid alterations in
      endothelial focal contacts.
AB  - Transmigrated polymorphonuclear leukocytes (PMNs) usually undergo subendothelial
      transverse migration before penetrating into inner tissue layers. Whether or how
      endothelial cells (ECs) respond to the PMN migrating underneath them is unknown.
      A tissue flow chamber was used to establish a fMLP gradient and to observe PMN
      transverse migration along with its associated endothelial responses in culture
      (on a collagen gel) or in vascular tissues. Our results indicated that
      transversely migrating PMNs were in direct contact with the basal side of ECs.
      Contrasting to focal adhesion kinase (FAK) or proteins with phosphorylated
      tyrosine, paxillin disappeared rapidly (<1 min) from endothelial focal contacts
      after encountering the leukocyte's leading edge and soon rejoined them after the
      PMN had left. In addition, FAK moved away or became dephosphorylated when PMNs
      remained at the same subendothelial location for longer than 10 min, leaving
      actin filaments apparently unaltered. Unlike PMN transendothelial migration, PMN
      transverse migration did not induce any detectable endothelial calcium signaling.
      Taken together, our findings indicated that PMN transverse migration interrupted
      endothelial-matrix interactions and induced rapid alterations in endothelial
      focal contact composition.

PMID- 17554016
TI  - Proteolytic cleavage of glycoprotein B is dispensable for in vitro replication,
      but required for syncytium formation of pseudorabies virus.
AB  - Glycoprotein B (gB) is the most conserved glycoprotein among herpesviruses and it
      plays important roles in virus infectivity. In most herpesviruses, including
      pseudorabies virus (PRV), gB is cleaved by a cellular protease into two disulfide
      linked subunits. In the present study, I found that the PRV gB generated in human
      colon carcinoma LoVo cells, which lack the ubiquitous protease furin, remained in
      the uncleaved form and the virus replicated in these cells without cell fusion.
      The uncleaved gB was converted into its subunits after furin digestion. The virus
      also replicated in Madin-Darby bovine kidney cells without cell fusion in the
      presence of a furin inhibitor, whereas distinct syncytia were formed in the
      absence of the inhibitor. LoVo cells constitutively expressing furin showed cell
      fusion when they were infected with the virus. Penetration kinetics assays
      revealed that the virus carrying uncleaved gB penetrated the cells at the same
      rate as the virus carrying cleaved gB. These results indicate that PRV gB is
      cleaved by furin and that the cleavage is dispensable for virus replication in
      vitro. Furthermore, gB cleavage is involved in syncytium formation but not in
      penetration kinetics, suggesting that different mechanisms operate between cell
      cell fusion and virus-cell fusion by PRV.

PMID- 17554017
TI  - Susceptibility of cancer cells to herpes simplex virus-dependent apoptosis.
AB  - Apoptosis has recently been associated with herpes simplex virus 1 (HSV-1)
      latency and disease severity. There is an intricate balance between pro- and anti
      apoptotic processes during HSV-1 infection. When anti-apoptotic pathways are
      suppressed, this balance is upset and the cells die by apoptosis, referred to
      here as HSV-1-dependent apoptosis (HDAP). It has been observed previously that
      HeLa cancer cells exhibit an enhanced sensitivity to HDAP. Here, a series of
      specific patient-derived cancer cells was utilized to investigate the cell-type
      specificity of HDAP. The results showed that a human mammary tumour cell line was
      sensitive to HDAP, whilst syngeneic normal cells were resistant. Furthermore, low
      passage-number primary human mammary epithelial cells were resistant to HDAP.
      When the susceptibility of human colon, brain, breast and cervical cancer cells
      was assessed, the only cells insensitive to HDAP were those resistant to all
      environmental stimuli tested. This implies that the HDAP resistance was probably
      due to mutations in the cellular apoptotic machinery. Thus, the susceptibility of
      cancer cells to HDAP requires that they possess a functional ability to undergo
      programmed cell death.

PMID- 17554018
TI  - Epstein-Barr virus induces a distinct form of DNA-bound STAT1 compared with that
      found in interferon-stimulated B lymphocytes.
AB  - Since 'constitutive activation' of STAT1 was first described in Epstein-Barr
      virus (EBV)-immortalized lymphoblastoid cell lines (LCLs), there has been
      controversy regarding the molecular identity of the STAT1 DNA-binding complex
      found in these cells. The post-translational modifications of STAT1 in LCLs have
      been analysed and an LMP1-induced STAT1 DNA-binding complex, different from that
      generated by alpha interferon (IFN) stimulation and not involving tyrosine
      phosphorylation, is demonstrated. STAT1 is serine-phosphorylated downstream of
      PI3K and MEK in LCLs and this modification restricts IFN-stimulated STAT1-DNA
      binding. These data suggest that EBV induces a distinct form of DNA-bound STAT1
      in virus-infected cells.

PMID- 17554019
TI  - Activity of the LMP1 gene promoter in Epstein-Barr virus-transformed cell lines
      is modulated by sequence variations in the promoter-proximal CRE site.
AB  - The Epstein-Barr virus (EBV)-encoded tumour-associated latent membrane protein 1
      (LMP1) gene expression is transactivated by EBV nuclear antigen 2 (EBNA2) in
      human B cells. We have previously identified a cyclic AMP-responsive element
      (CRE) in the B95-8 LMP1 promoter that is essential for transcription activation.
      Sequencing of LMP1 promoter in the P3HR1-derived EREB2.5 cell line revealed 25
      single base pair substitutions in comparison to the B95-8 virus, one of them
      localized in the CRE element. Sequence variations in this element have been
      identified in several EBV isolates of both African and Asian origins. The effect
      of the P3HR1 CRE site variation on binding of factors to the LMP1 promoter
      sequence (LRS) and promoter activation was investigated with electrophoretic
      mobility-shift assays and reporter gene transfection assays. ATF1 and CREB1
      transcription factors bound with reduced efficiency to the P3HR1 variant and
      below the detection level to the other tested variants. Accordingly, reporter
      plasmids carrying the P3HR1 CRE sequence in a B95-8 LRS context displayed 50 %
      lower activity in all tested cell lines. The impaired ability to activate
      transcription caused by the C to A substitution in CRE was not apparent when the
      mutated site was placed in a P3HR1 LRS context and the reporter transfected into
      Jijoye cells, most likely as a consequence of the other base pair substitutions
      in P3HR1 LRS. Overall, our results suggest that the mutations in the LRS CRE site
      have been conserved to adjust LMP1 expression to levels that favour cell survival
      in certain cellular and environmental contexts.

PMID- 17554020
TI  - Murine gammaherpesvirus-68 productively infects immature dendritic cells and
      blocks maturation.
AB  - Many viruses have evolved mechanisms to evade host immunity by subverting the
      function of dendritic cells (DCs). This study determined whether murine
      gammaherpesvirus-68 (gamma HV-68) could infect immature or mature bone-marrow
      derived DCs and what effect infection had on DC maturation. It was found that
      gamma HV-68 productively infected immature DCs, as evidenced by increased viral
      titres over time. If DCs were induced to mature by exposure to LPS and then
      infected with gamma HV-68, only a small percentage of cells was productively
      infected. However, limiting-dilution assays to measure viral reactivation
      demonstrated that the mature DCs were latently infected with gamma HV-68.
      Electron microscopy revealed the presence of capsids in the nucleus of immature
      DCs but not in mature DCs. Interestingly, infection of immature DCs by gamma HV
      68 did not result in upregulation of the co-stimulatory molecules CD80 and CD86
      or MHC class I and II, or induce cell migration, suggesting that the virus
      infection did not induce DC maturation. Furthermore, gamma HV-68 infection of
      immature DCs did not result in elevated interleukin-12, an important cytokine in
      the induction of T-cell responses. Finally, lipopolysaccharide and poly(I : C)
      stimulation of gamma HV-68-infected immature DCs did not induce increases in the
      expression of co-stimulatory molecules and MHC class I or II compared with mock
      treated cells, suggesting that gamma HV-68 infection blocked maturation. Taken
      together, these data demonstrate that gamma HV-68 infection of DCs differs
      depending on the maturation state of the DC. Moreover, the block in DC maturation
      suggests a possible immunoevasion strategy by gamma HV-68.

PMID- 17554021
TI  - Genomic sequence of a clonal isolate of the vaccinia virus Lister strain employed
      for smallpox vaccination in France and its comparison to other orthopoxviruses.
AB  - Since 1980 there has been global eradication of smallpox due to the success of
      the vaccination programme using vaccinia virus (VACV). During the eradication
      period, distinct VACV strains circulated, the Lister strain being the most
      commonly employed in Europe. Analysis of the safety of smallpox vaccines has
      suggested that they display significant heterogeneity. To gain a more detailed
      understanding of the diversity of VACV strains it is important to determine their
      genomic sequences. Although the sequences of three isolates of the Japanese
      Lister original strain (VACV-LO) are available, no analysis of the relationship
      of any Lister sequence compared to other VACV genomes has been reported. Here, we
      describe the sequence of a representative clonal isolate of the Lister vaccine
      (VACV-List) used to inoculate the French population. The coding capacity of VACV
      List was compared to other VACV strains. The 201 open reading frames (ORFs) were
      annotated in the VACV-List genome based on protein size, genomic localization and
      prior characterization of many ORFs. Eleven ORFs were recognized as pseudogenes
      as they were truncated or fragmented counterparts of larger ORFs in other
      orthopoxviruses (OPVs). The VACV-List genome also contains several ORFs that have
      not been annotated in other VACVs but were found in other OPVs. VACV-List and
      VACV-LO displayed a high level of nucleotide sequence similarity. Compared to the
      Copenhagen strain of VACV, the VACV-List sequence diverged in three main regions,
      one of them corresponding to a substitution in VACV-List with coxpox virus GRI-90
      strain ORFs, suggestive of prior genetic exchanges. These studies highlight the
      heterogeneity between VACV strains and provide a basis to better understand
      differences in safety and efficacy of smallpox vaccines.

PMID- 17554022
TI  - Vaccinia virus gene F3L encodes an intracellular protein that affects the innate
      immune response.
AB  - The Vaccinia virus BTB/kelch protein F3 has been characterized and its effects on
      virus replication in vitro and virus virulence in vivo have been determined. The
      loss of the F3L gene had no effect on virus growth, plaque phenotype or
      cytopathic effect in cell culture under the conditions tested. However, the
      virulence of a virus lacking F3L in an intradermal model was reduced compared
      with controls, and this was demonstrated by a significantly smaller lesion and
      alterations to the innate immune response to infection. The predicted molecular
      mass of the F3 protein is 56 kDa; however, immunoblotting of infected cell
      lysates using an antibody directed against recombinant F3 revealed two proteins
      of estimated sizes 37 and 25 kDa.

PMID- 17554023
TI  - Infection with recombinant orf viruses demonstrates that the viral interleukin-10
      is a virulence factor.
AB  - Orf virus is the prototype parapoxvirus that causes the contagious skin disease
      orf. It encodes an orthologue of the cytokine interleukin (IL)-10. Recombinant
      orf viruses were constructed in which the viral interleukin-10 (vorfIL-10) was
      disabled (vorfIL-10ko) and reinserted (vorfrevIL-10) at the same locus and
      compared to wild-type virus for their ability to induce skin lesions in sheep.
      After either primary infection or reinfection, smaller less severe lesions were
      recorded in the vorfIL-10ko-infected animals compared with either of the vorfIL
      10-intact virus-infected animals. Thus, the vorfIL-10ko virus was attenuated
      compared with the vorfIL-10 intact viruses, demonstrating that orf virus IL-10 is
      a virulence factor. The virus IL-10 is one of several virulence or immuno
      modulatory factors expressed by orf virus. Removal of any one of these genes
      would be expected to have only a partial effect on virulence, which is what was
      observed in this study with vorfIL-10.

PMID- 17554024
TI  - Genital warts in Burmeister's porpoises: characterization of Phocoena spinipinnis
      papillomavirus type 1 (PsPV-1) and evidence for a second, distantly related PsPV.
AB  - We identified sequences from two distantly related papillomaviruses in genital
      warts from two Burmeister's porpoises, including a PV antigen-positive specimen,
      and characterized Phocoena spinipinnis papillomavirus type 1 (PsPV-1). The PsPV-1
      genome comprises 7879 nt and presents unusual features. It lacks an E7, an E8 and
      a bona fide E5 open reading frame (ORF) and has a large E6 ORF. PsPV-1 L1 ORF
      showed the highest percentage of nucleotide identity (54-55 %) with human
      papillomavirus type 5, bovine papillomavirus type 3 (BPV-3) and Tursiops
      truncatus papillomavirus type 2 (TtPV-2). This warrants the classification of
      PsPV-1 as the prototype of the genus Omikronpapillomavirus. PsPV-1 clustered with
      TtPV-2 in the E6 and E1E2 phylogenetic trees and with TtPV-2 and BPV-3 in the
      L2L1 tree. This supports the hypothesis that PV evolution may not be monophyletic
      across all genes.

PMID- 17554025
TI  - Complete genome and phylogenetic position of bovine papillomavirus type 7.
AB  - Six bovine papillomavirus (BPV) types and 16 putative BPV types have been
      reported previously. Here, the complete genome sequence of BAPV6, a novel
      putative BPV type isolated from cattle in Japan, was determined by using multiple
      primed rolling-circle amplification. The genome consisted of 7412 bp (G+C content
      of 46 mol%) that encoded five early (E1, E2, E4, E6 and E7) and two late (L1 and
      L2) genes, but did not encode the E5 gene. The E6 protein contained a non
      consensus CxxC(x)(33)CxxC and a consensus CxxC(x)(29)CxxC zinc-binding domain,
      and the E7 protein lacked the LxCxE motif. The nucleotide sequence of the L1 open
      reading frame (ORF) was related most closely (57-58 %) to the L1 ORF of member(s)
      of the genera Betapapillomavirus, Gammapapillomavirus and Pipapillomavirus.
      Phylogenetic analysis based on the complete L1 ORF suggests that BAPV6 should be
      classified in a novel genus in the family Papillomaviridae as BPV-7.

PMID- 17554026
TI  - Identification and genomic characterization of a novel human torque teno virus of
      3.2 kb.
AB  - In the process of searching for the recently described small anelloviruses 1 and
      2 (SAVs) with the genomic DNA length of 2.2 or 2.6 kb in human sera, we isolated
      a novel virus with its genomic organization resembling those of torque teno virus
      (TTV) of 3.8-3.9 kb and torque teno mini virus (TTMV) of 2.8-2.9 kb. The entire
      genomic sequence of three isolates (MD1-032, MD1-073 and MD2-013), which
      comprised 3242-3253 bases and exhibited 76-99 % identities with the SAVs within
      the overlapping sequence, was determined. Although the MD1-032, MD1-073 and MD2
      013 isolates differed by 10-28 % from each other over the entire genome, they
      segregated into the same cluster and were phylogenetically distinguishable from
      all reported TTVs and TTMVs. These results suggest that SAVs are deletion mutants
      of the novel virus with intermediate genomic length between those of TTV and TTMV
      and that the novel virus can be classified into a third group of the genus
      Anellovirus.

PMID- 17554027
TI  - In vivo replication kinetics and transcription patterns of the
      nucleopolyhedrovirus (NeabNPV) of the balsam fir sawfly, Neodiprion abietis.
AB  - DNA replication and transcription of NeabNPV, the nucleopolyhedrovirus (NPV) of
      the balsam fir sawfly, Neodiprion abietis (Hymenoptera: Diprionidae), in host
      larvae were investigated. NPV DNA replication kinetics and gene-expression
      patterns have been resolved only in lepidopteran cell-culture systems and in
      limited in vivo experiments with lepidopteran larvae. Furthermore, there are
      significant differences in pathologies caused by lepidopteran NPVs, which
      replicate in many tissues, and hymenopteran NPVs, known to replicate in midgut
      epithelium only. Despite the differences in host specificity and pathology,
      NeabNPV DNA replication kinetics were similar to those reported for lepidopteran
      NPVs. Maximal NeabNPV DNA synthesis was observed between 4 and 24 h post
      inoculation (p.i.) but, in contrast to lepidopteran NPVs, synthesis continued at
      a lower rate up to 72 h p.i. Selected NeabNPV genes exhibited a cascade pattern
      of transcription similar to that of lepidopteran NPVs. RT-PCR products of the
      NeabNPV lef-1, lef-2 and dnapol transcripts were observed as early as 2 h p.i.,
      whilst lef-8 and lef-9, encoding putative viral RNA polymerase subunits, were
      detected at 1 and 6 h p.i., respectively. Two structural late transcripts (gp41
      and p74) were observed from 6 h p.i. The very late factor 1 (vlf-1) transcript, a
      transactivator of very late genes, was observed from 12 h p.i., but the very late
      transcript polh, encoding the major occlusion protein, polyhedrin, was observed
      from 24 h p.i. This study provides the first insight into DNA replication and
      gene expression of a non-lepidopteran baculovirus.

PMID- 17554028
TI  - Virulence of a mouse-adapted Semliki Forest virus strain is associated with
      reduced susceptibility to interferon.
AB  - Type I interferons (IFNs) are essential components of the innate immune system.
      This study characterized the distinct IFN sensitivities of two closely related
      Semliki Forest virus (SFV) strains in cell culture. The virulent L10 strain was
      derived from the original virus isolate by propagation in mice. In contrast, the
      avirulent SFV strain, designated V42, was derived from an earlier passage of the
      original virus isolated from mosquitoes. The virulent L10 strain produced a
      cytopathic effect (CPE) in IFN-treated cells and the production of infectious
      virus was only two orders of magnitude lower compared with untreated cells. In
      contrast, the avirulent V42 exerted no CPE in IFN-treated cells and production of
      infectious virus was four orders of magnitude lower compared with untreated
      cells. The reduced CPE in IFN-treated cells infected with the avirulent V42
      strain was due to inhibition of productive infection and not to reduced cell
      death. The virulent L10 strain synthesized less genomic RNA but more non
      structural proteins than the avirulent V42 strain, suggesting more efficient
      translation of the L10 genomic RNA. Using a cell line unable to produce IFN, it
      was shown that the reduced susceptibility of the L10 strain to the action of IFN
      was not due to reduced IFN induction. Hence, the reduced susceptibility of the
      virulent L10 strain to the action of IFN allows it to overcome the established
      IFN-induced antiviral state of the cell, thereby increasing its virulence.

PMID- 17554029
TI  - Co-circulation of multiple rubella virus strains in Belarus forming novel genetic
      groups within clade 1.
AB  - Although the WHO recommends a comprehensive genetic characterization, little is
      known about circulating strains and genotypes of rubella virus (RUBV) for many
      European countries. Studies investigating the genetic diversity of a sizeable
      number of strains from a certain location are rare. This study presents the first
      molecular characterization of isolates from Belarus. Throat swab and urine
      samples were collected between 2004 and 2005 from patients presenting in two
      infectious disease hospitals and three outpatient clinics in and around Minsk. In
      total, 14 isolates were obtained from this clinical material. Phylogenetic
      analysis of the E1 gene sequence of these isolates showed that three distinct
      groups of RUBV strains co-circulated. One group of isolates was assigned to
      genotype 1E, whereas the other two did not group with any of the recognized
      genotypes but grouped with a strain belonging to the provisional genotype 1g.
      Detailed analysis showed that the group comprising 1g strains also contained
      sequences formerly attributed to genotype 1B and could be divided into four
      subgroups, one of which might represent a putative novel provisional genotype of
      clade 1. These findings show that three distinct strains with limited variability
      are present in Belarus, suggesting independent introductory events. As there
      currently seem to be misattributions of strains to genotypes and unclear
      phylogenetic relationships, criteria for genotyping of RUBV should be clarified
      further.

PMID- 17554030
TI  - Genetic divergence of Chikungunya viruses in India (1963-2006) with special
      reference to the 2005-2006 explosive epidemic.
AB  - Re-emergence of Chikungunya (CHIK), caused by CHIK virus, was recorded in India
      during 2005-2006 after a gap of 32 years, causing 1.3 million cases in 13 states.
      Several islands of the Indian Ocean reported similar outbreaks in the same
      period. These outbreaks were attributed to the African genotype of CHIK virus. To
      examine relatedness of the Indian isolates (IND-06) with Reunion Island isolates
      (RU), full-genome sequences of five CHIK virus isolates representative of
      different Indian states were determined. In addition, an isolate obtained from
      mosquitoes in the year 2000 (Yawat-2000), identified as being of the African
      genotype, and two older strains isolated in 1963 and 1973 (of the Asian
      genotype), were sequenced. The IND-06 isolates shared 99.9 % nucleotide identity
      with RU isolates, confirming involvement of the same strain in these outbreaks.
      The IND-06 isolates shared 98.2 % identity with the Yawat-2000 isolate. Of two
      crucial substitutions reported for RU isolates in the E1 region, M269V was noted
      in the Yawat-2000 and IND-06 isolates, whereas D284E was seen only in the IND-06
      isolates. The A226V shift observed with the progression of the epidemic in
      Reunion Island, probably associated with adaptation to the mosquito vector, was
      absent in all of the Indian isolates. Three unique substitutions were noted in
      the IND-06 isolates: two (T128K and T376M) in the Nsp1 region and one (P23S) in
      the capsid protein. The two Asian strains showed 99.4 % nucleotide identity to
      each other, indicating relative stability of the virus. No evidence of
      recombination of the Asian and African genotypes, or of positive selection was
      observed. The results may help in understanding the association, if any, of the
      unique mutations with the explosive nature of the CHIK outbreak.

PMID- 17554031
TI  - Mutations at the palmitoylation site of non-structural protein nsP1 of Semliki
      Forest virus attenuate virus replication and cause accumulation of compensatory
      mutations.
AB  - The replicase of Semliki Forest virus (SFV) consists of four non-structural
      proteins, designated nsP1-4, and is bound to cellular membranes via an
      amphipathic peptide and palmitoylated cysteine residues of nsP1. It was found
      that mutations preventing nsP1 palmitoylation also attenuated virus replication.
      The replacement of these cysteines by alanines, or their deletion, abolished
      virus viability, possibly due to disruption of interactions between nsP1 and
      nsP4, which is the catalytic subunit of the replicase. However, during a single
      infection cycle, the ability of the virus to replicate was restored due to
      accumulation of second-site mutations in nsP1. These mutations led to the
      restoration of nsP1-nsP4 interaction, but did not restore the palmitoylation of
      nsP1. The proteins with palmitoylation-site mutations, as well as those
      harbouring compensatory mutations in addition to palmitoylation-site mutations,
      were enzymically active and localized, at least in part, on the plasma membrane
      of transfected cells. Interestingly, deletion of 7 aa including the
      palmitoylation site of nsP1 had a relatively mild effect on virus viability and
      no significant impact on nsP1-nsP4 interaction. Similarly, the change of cysteine
      to alanine at the palmitoylation site of nsP1 of Sindbis virus had only a mild
      effect on virus replication. Taken together, these findings indicate that nsP1
      palmitoylation as such is not the factor determining the ability to bind to
      cellular membranes and form a functional replicase complex. Instead, these
      abilities may be linked to the three-dimensional structure of nsP1 and the
      capability of nsP1 to interact with other components of the viral replicase
      complex.

PMID- 17554032
TI  - Absence of viral escape within a frequently recognized HLA-A26-restricted CD8+ T
      cell epitope targeting the functionally constrained hepatitis C virus NS5A/5B
      cleavage site.
AB  - CD8(+) T-cell responses are central for the resolution of hepatitis C virus (HCV)
      infection, and viral escape from these CD8(+) T-cell responses has been suggested
      to play a major role in HCV persistence. However, the factors determining the
      emergence of CD8 escape mutations are not well understood. Here, the first
      identification of four HLA-A26-restricted CD8(+) T-cell epitopes is reported. Of
      note, two of these four epitopes are located in the NS3/4A and NS5A/5B cleavage
      sites. The latter epitope is targeted in all (three of three) patients with
      acute, resolving HCV infection and in a relatively high proportion (four of 14)
      of patients with chronic HCV infection. Importantly, the epitope corresponding to
      the NS5A/5B cleavage site is characterized by the complete absence of sequence
      variations, despite the presence of functional virus-specific CD8(+) T cells in
      our cohort. These results support previous findings that showed defined
      functional constraints within this region. They also suggest that the absence of
      viral escape may be determined by viral fitness cost and highlight an attractive
      target for immunotherapies.

PMID- 17554033
TI  - Hepatitis C virus internal ribosome entry site initiates protein synthesis at the
      authentic initiation codon in yeast.
AB  - Hepatitis C virus (HCV) is an important pathogen causing both acute and chronic
      infections in humans. The HCV polyprotein is synthesized by cap-independent
      translation initiation after ribosome binding to the highly structured internal
      ribosome entry site (IRES). The HCV IRES has been shown to have a low requirement
      for translation initiation factors and the ability to bind directly to the 40S
      ribosomal subunit. A novel yeast bicistronic reporter system, suitable for
      sensitive and accurate analysis of IRES activity, has been developed. It employs
      signal amplification based on the Gal4p transcription factor-mediated activation
      of a variety of secondary reporter genes. The system has a broad dynamic range
      and, depending on the nature of the particular secondary reporter, can be used
      both for precise measurements of IRES activity and for selection and screening
      for novel IRES variants and IRES trans-acting factors. By using this novel
      bicistronic system, it was shown that the HCV IRES is functional in yeast cells.
      Mutational analysis of the IRES loop IV and the adjacent region revealed that, in
      yeast, as in mammalian cells, translation initiates preferentially at the
      authentic (342)AUG codon and that disruption of the HCV IRES loop IV abrogates
      its function, whilst minor positional changes or substitutions of the initiation
      codon within loop IV are largely tolerated. These findings bring more general
      insights to translation initiation, but also open the door for utilization of
      yeast and its sophisticated genetics for searching for new antiviral drugs and
      HCV IRES trans-acting proteins.

PMID- 17554034
TI  - Universal and mutation-resistant anti-enteroviral activity: potency of small
      interfering RNA complementary to the conserved cis-acting replication element
      within the enterovirus coding region.
AB  - The promising potential of RNA interference-based antiviral therapies has been
      well established. However, the antiviral efficacy is largely limited by genomic
      diversity and genetic instability of various viruses, including human enterovirus
      B (HEB). In this work, the first evidence supporting the anti-HEB activity of the
      small interfering RNA (siRNA) targeting the highly conserved cis-acting
      replication element (CRE) within virus coding region 2C is presented. HeLa cells
      pre-treated with siRNA complementary to the conserved sequence of the loop region
      of CRE(2C) were effectively rescued from the cytopathic effects of HEBs.
      Downregulation of virus replication and attenuation of cytotoxicity were
      consistently observed in various reference strains and clinical isolates. Cells
      treated with this siRNA were resistant to the emergence of viable escape mutants
      and showed sustained antiviral ability. Collectively, the data suggest that the
      siRNA based on the disordered structure within the highly conserved cis-acting
      coding region has potential as a universal, persistent anti-HEB agent. The same
      strategy can be successfully applied to the development of siRNA with consistent
      antiviral effects in other virus groups possessing similar RNA elements.

PMID- 17554035
TI  - Differential cleavage of the norovirus polyprotein precursor by two active forms
      of the viral protease.
AB  - Protein translation in noroviruses requires translational processing of a
      polyprotein precursor by the viral protease. So far, the molecular mechanisms of
      catalytic cleavage by the viral protease are poorly understood. In this study,
      the catalytic activities and substrate specificities of the viral protease were
      examined in vitro by using synthetic peptides (11-15 residues) corresponding to
      the cleavage sites of the norovirus polyprotein. Both predicted forms of the
      viral protease, the 3C-like protease (3C(pro)) and the 3CD-like protease
      polymerase protein (3CD(propol)), displayed a specific trans cleavage activity of
      peptides bearing Gln-Gly at the scissile bond. In contrast, peptides bearing Glu
      Gly at the scissile bond (p20/VPg and 3C(pro)/3D(pol) junctions) were resistant
      to trans-cleavage by 3C(pro) and 3CD(propol). Interestingly, the VPg/3C(pro)
      scissile bond (Glu-Ala) was cleaved only by 3CD(propol), and examination of
      relative cleavage efficiencies revealed significant differences in processing of
      peptides, indicating differential cleavage patterns for 3C(pro) and 3CD(propol).

PMID- 17554036
TI  - Rescue of a chimeric rinderpest virus with the nucleocapsid protein derived from
      peste-des-petits-ruminants virus: use as a marker vaccine.
AB  - The nucleocapsid (N) protein of all morbilliviruses has a highly conserved
      central region that is thought to interact with and encapsidate the viral RNA.
      The C-terminal third of the N protein is highly variable among morbilliviruses
      and is thought to be located on the outer surface and to be available to interact
      with other viral proteins such as the phosphoprotein, the polymerase protein and
      the matrix protein. Using reverse genetics, a chimeric rinderpest virus
      (RPV)/peste-des-petits-ruminants virus (PPRV) was rescued in which the RPV N gene
      open reading frame had been replaced with that of PPRV (RPV-PPRN). The chimeric
      virus maintained efficient replication in cell culture. Cattle vaccinated with
      this chimeric vaccine showed no adverse reaction and were protected from
      subsequent challenge with wild-type RPV, indicating it to be a safe and
      efficacious vaccine. The carboxyl-terminal variable region of the rinderpest N
      protein was cloned and expressed in Escherichia coli. The expressed protein was
      used to develop an indirect ELISA that could clearly differentiate between RPV-
      and PPRV-infected animals. The possibility of using this virus as a marker
      vaccine in association with a new diagnostic ELISA in the rinderpest eradication
      programme is discussed.

PMID- 17554037
TI  - Infection of cynomolgus macaques (Macaca fascicularis) and rhesus macaques
      (Macaca mulatta) with different wild-type measles viruses.
AB  - Both rhesus and cynomolgus macaques have been used as animal models for measles
      vaccination and immunopathogenesis studies. A number of studies have suggested
      that experimental measles virus (MV) infection induces more-characteristic
      clinical features in rhesus than in cynomolgus monkeys. In the present study,
      both macaque species were infected with two different wild-type MV strains and
      clinical, virological and immunological parameters were compared. The viruses
      used were a genotype C2 virus isolated in The Netherlands in 1991 (MV-Bil) and a
      genotype B3 virus isolated from a severe measles case in Sudan in 1997 (MV
      Sudan). Following infection, all rhesus monkeys developed a skin rash and
      conjunctivitis, which were less obvious in cynomolgus monkeys. Fever was either
      mild or absent in both species. Virus reisolation profiles from peripheral blood
      mononuclear cells and broncho-alveolar lavage cells and the kinetics of MV
      specific IgM and IgG responses were largely identical in the two animal species.
      However, in animals infected with MV-Sudan, viraemia appeared earlier and lasted
      longer than in animals infected with MV-Bil. This was also reflected by the
      earlier appearance of MV-specific serum IgM antibodies after infection with MV
      Sudan. Collectively, these data show that cynomolgus and rhesus macaques are
      equally susceptible to wild-type MV infection, although infection in the skin
      seems to follow a different course in rhesus macaques. MV-Sudan proved more
      pathogenic for non-human primates than MV-Bil, which may render it more suitable
      for use in future pathogenesis studies.

PMID- 17554038
TI  - Antigenic and genetic characterization of H9N2 swine influenza viruses in China.
AB  - As pigs are susceptible to infection with both avian and human influenza A
      viruses, they have been proposed to be an intermediate host for the generation of
      pandemic virus through reassortment. Antigenic and genetic characterization was
      performed for five swine H9N2 influenza viruses isolated from diseased pigs from
      different farms. The haemagglutinin (HA) antigenicity of swine H9N2 viruses was
      different from that of chicken H9N2 viruses prevalent in northern China. Genetic
      analysis revealed that all five isolates had an RLSR motif at the cleavage site
      of HA, which was different from those of A/duck/Hong Kong/Y280/97 (Dk/HK/Y280/97)
      like viruses established in chickens in China. Phylogenetic analyses indicated
      that the five swine H9N2 viruses formed novel HA and neuraminidase sublineages
      that were related closely to those of earlier chicken H9 viruses and were also
      consistent with the extent of the observed antigenic variation. The six internal
      genes of the isolates possessed H5N1-like sequences, indicating that they were
      reassortants of H9 and H5 viruses. The present results indicate that avian to
      porcine interspecies transmission of H9N2 viruses might have resulted in the
      generation of viruses with novel antigenic and genetic characteristics;
      therefore, surveillance of swine influenza should be given a high priority.

PMID- 17554039
TI  - Molecular epidemiology of vesicular stomatitis New Jersey virus from the 2004
      2005 US outbreak indicates a common origin with Mexican strains.
AB  - Vesicular stomatitis (VS) outbreaks of unknown origin occur at 8-10-year
      intervals in the south-western USA with the most recent outbreak beginning in
      2004. A previous study has suggested that strains causing US outbreaks are
      closely related to strains causing outbreaks in Mexico [Rodriguez (2002) Virus
      Res 85, 211-219]. This study determined the phylogenetic relationships among 116
      vesicular stomatitis New Jersey virus (VSNJV) strains obtained from the 2004
      outbreak and from endemic areas in Mexico. All 69 US viruses showed little
      sequence divergence (<or=1.3 %), regardless of their location or time of
      collection, and clustered with 11 Mexican viruses into a genetic lineage not
      previously present in the USA. Furthermore, viruses with identical phosphoprotein
      hypervariable region sequences to those causing the US outbreaks in 1995-1997 and
      2004-2005 were found circulating in Mexico between 2002 and 2004. Molecular
      adaptation analysis provided evidence for positive selection in the
      phosphoprotein and glycoprotein genes during a south-to-north migration among 69
      US viruses collected between the spring and autumn of 2004 and 2005. Phylogenetic
      data, temporal-spatial distribution and the finding of viral strains identical to
      those causing major outbreaks in the USA circulating in Mexico demonstrated that
      VS outbreaks in the south-western USA are the result of the introduction of viral
      strains from endemic areas in Mexico.

PMID- 17554040
TI  - Bovine leukemia virus protease: comparison with human T-lymphotropic virus and
      human immunodeficiency virus proteases.
AB  - Bovine leukemia virus (BLV) is a valuable model system for understanding human T
      lymphotropic virus 1 (HTLV-1); the availability of an infectious BLV clone,
      together with animal-model systems, will help to explore anti-HTLV-1 strategies.
      Nevertheless, the specificity and inhibitor sensitivity of the BLV protease (PR)
      have not been characterized in detail. To facilitate such studies, a molecular
      model for the enzyme was built. The specificity of the BLV PR was studied with a
      set of oligopeptides representing naturally occurring cleavage sites in various
      retroviruses. Unlike HTLV-1 PR, but similar to the human immunodeficiency virus 1
      (HIV-1) enzyme, BLV PR was able to hydrolyse the majority of the peptides, mostly
      at the same position as did their respective host PRs, indicating a broad
      specificity. When amino acid residues of the BLV PR substrate-binding sites were
      replaced by equivalent ones of the HIV-1 PR, many substitutions resulted in
      inactive protein, indicating a great sensitivity to mutations, as observed
      previously for the HTLV-1 PR. The specificity of the enzyme was studied further
      by using a series of peptides containing amino acid substitutions in a sequence
      representing a naturally occurring HTLV-1 PR cleavage site. Also, inhibitors of
      HIV-1 PR, HTLV-1 PR and other retroviral proteases were tested on the BLV PR.
      Interestingly, the BLV PR was more susceptible than the HTLV-1 PR to the
      inhibitors tested. Therefore, despite the specificity differences, in terms of
      mutation intolerance and inhibitor susceptibility of the PR, BLV and the
      corresponding animal-model systems may provide good models for testing of PR
      inhibitors that target HTLV-1.

PMID- 17554041
TI  - Induction of nitric oxide synthase by rotavirus enterotoxin NSP4: implication for
      rotavirus pathogenicity.
AB  - Rotavirus non-structural protein (NSP) 4 can induce aqueous secretion in the
      gastrointestinal tract of neonatal mice through activation of an age- and Ca(2+)
      dependent plasma membrane anion permeability. Accumulating evidence suggests that
      nitric oxide (NO) plays a role in the modulation of aqueous secretion and the
      barrier function of intestinal cells. This study investigated transcriptional
      changes in inducible NO synthase (iNOS), an enzyme responsible for NO production,
      after rotavirus infection in mice and after treatment of intestinal cells with
      NSP4. Diarrhoea was observed in 5-day-old CD-1 mice from days 1 to 3 after
      inoculation with 10(7) focus-forming units of different rotavirus strains. Ileal
      iNOS mRNA expression was induced as early as 6 h post-inoculation, before the
      onset of clinical diarrhoea in infected mice, and was upregulated during the
      course of rotavirus-induced diarrhoea. Ex vivo treatment of ilea excised from CD
      1 suckling mice with NSP4 resulted in upregulation of ileal iNOS mRNA expression
      within 4 h. Furthermore, NSP4 was able to induce iNOS expression and NO
      production in murine peritoneal macrophages and RAW264.7 cells. The specificity
      of NSP4 inducibility was confirmed by the inhibitory effect of anti-NSP4 serum.
      Using a series of truncated NSP4s, the domain responsible for iNOS induction in
      macrophages was mapped to the reported enterotoxin domain, aa 109-135. Thus,
      rotavirus infection induces ileal iNOS expression in vivo and rotavirus NSP4 also
      induces iNOS expression in the ileum and macrophages. Together, these findings
      suggest that NO plays a role in rotavirus-induced diarrhoea.

PMID- 17554042
TI  - Genomic regions of tomato leaf curl virus DNA satellite required for replication
      and for satellite-mediated delivery of heterologous DNAs.
AB  - Tomato leaf curl virus (TLCV) satellite DNA (sat-DNA) is a 682 nt, circular,
      single-stranded molecule that lacks an open reading frame (ORF) or an apparent
      promoter. It contains binding motifs for the TLCV replication-associated protein,
      but these are dispensable for replication. To identify the regions of the sat-DNA
      critical for replication, the entire sequence was scanned by deletion/replacement
      mutagenesis. Transient assays using Nicotiana benthamiana revealed that sequences
      within nt 296-35 (through nt 682) are essential for replication. Sequence
      deletions and replacements between nt 35 and 296 were tolerated but with a
      significant loss of infectivity, indicating that genome size strongly influences
      replication efficiency. Within the permissible region, inserts of 100-700 nt were
      retained in transient assays although with a slight reduction in replication. In
      addition, sat-DNA constructs containing short non-viral DNAs replicated and
      spread in tobacco plants, indicating their potential as gene-delivery vectors.

PMID- 17554043
TI  - PrPCWD in rectal lymphoid tissue of deer (Odocoileus spp.).
AB  - The utility of rectal lymphoid tissue sampling for the diagnosis of chronic
      wasting disease (CWD) infections in mule deer (Odocoileus hemionus) and white
      tailed deer (Odocoileus virginianus) was evaluated. CWD-associated prion protein
      (PrP(CWD)) deposits were observed in the rectal mucosa from 19 orally inoculated
      mule deer by 381 days post-inoculation (p.i.); similarly, 45 out of 50 naturally
      infected mule deer had PrP(CWD) in their rectal mucosa. In orally inoculated
      white-tailed deer, the presence of glycine (G) or serine (S) at codon 96 of the
      native PrP (denoted 96GG, 96GS or 96SS) appeared to influence the temporal
      patterns of PrP(CWD) deposition: nine out of 11 infected 96GG individuals had
      PrP(CWD) in their rectal mucosa by 342 days p.i., whereas only three out of seven
      infected 96GS individuals had PrP(CWD) in their rectal mucosa by 381 days p.i.
      and none of three 96SS individuals had PrP(CWD) in their rectal mucosa by 751
      days p.i. These findings support further evaluation of rectal mucosa sampling in
      CWD surveillance.

PMID- 17554044
TI  - Increased PrP mRNA expression in lymphoid follicles of the ileal Peyer's patch of
      sheep experimentally exposed to the scrapie agent.
AB  - To understand the functional role of cellular prion protein (PrP(C)) in the
      initiation and maintenance of prion disease within the host, it is important to
      obtain a more detailed understanding of PrP(C) transcription in tissues during
      the development of disease. Using an experimental model with oral infection, we
      examined the effect of scrapie and the accumulation of the scrapie related form
      of the prion protein (PrP(Sc)) on the expression level of PrP mRNA in the ileal
      Peyer's patch of sheep. In the early phase of infection, prior to PrP(Sc)
      accumulation, no effect on the PrP expression was detected. However, it was found
      that lambs with PrP genotypes associated with high susceptibility for scrapie
      generally had higher PrP mRNA levels than lambs with less susceptible genotypes.
      Further, in highly susceptible VRQ/VRQ sheep at a stage of disease with high
      accumulation of PrP(Sc), real-time RT-PCR and microdissection were used to
      investigate levels of PrP mRNA in four different tissue compartments. An
      increased level of PrP mRNA was found in lymphoid follicles of infected sheep
      compared with controls, indicating upregulation of PrP expression in the
      follicles to compensate for the loss of PrP(C) converted to PrP(Sc), or that
      PrP(Sc) accumulation directly or indirectly influences the PrP expression. Still,
      the PrP expression level in the follicles was low compared with the other
      compartments investigated, suggesting that although increased PrP expression
      could contribute to PrP(Sc) accumulation, other factors are also important in the
      processes leading to accumulation of PrP(Sc) in the follicles.

PMID- 17554045
TI  - Role of receptors in Bacillus thuringiensis crystal toxin activity.
AB  - Bacillus thuringiensis produces crystalline protein inclusions with insecticidal
      or nematocidal properties. These crystal (Cry) proteins determine a particular
      strain's toxicity profile. Transgenic crops expressing one or more recombinant
      Cry toxins have become agriculturally important. Individual Cry toxins are
      usually toxic to only a few species within an order, and receptors on midgut
      epithelial cells have been shown to be critical determinants of Cry specificity.
      The best characterized of these receptors have been identified for lepidopterans,
      and two major receptor classes have emerged: the aminopeptidase N (APN) receptors
      and the cadherin-like receptors. Currently, 38 different APNs have been reported
      for 12 different lepidopterans. Each APN belongs to one of five groups that have
      unique structural features and Cry-binding properties. While 17 different APNs
      have been reported to bind to Cry toxins, only 2 have been shown to mediate toxin
      susceptibly in vivo. In contrast, several cadherin-like proteins bind to Cry
      toxins and confer toxin susceptibility in vitro, and disruption of the cadherin
      gene has been associated with toxin resistance. Nonetheless, only a small subset
      of the lepidopteran-specific Cry toxins has been shown to interact with cadherin
      like proteins. This review analyzes the interactions between Cry toxins and their
      receptors, focusing on the identification and validation of receptors, the
      molecular basis for receptor recognition, the role of the receptor in resistant
      insects, and proposed models to explain the sequence of events at the cell
      surface by which receptor binding leads to cell death.

PMID- 17554046
TI  - A biochemical guide to yeast adhesins: glycoproteins for social and antisocial
      occasions.
AB  - Fungi are nonmotile eukaryotes that rely on their adhesins for selective
      interaction with the environment and with other fungal cells.
      Glycosylphosphatidylinositol (GPI)-cross-linked adhesins have essential roles in
      mating, colony morphology, host-pathogen interactions, and biofilm formation. We
      review the structure and binding properties of cell wall-bound adhesins of
      ascomycetous yeasts and relate them to their effects on cellular interactions,
      with particular emphasis on the agglutinins and flocculins of Saccharomyces and
      the Als proteins of Candida. These glycoproteins share common structural motifs
      tailored to surface activity and biological function. After being secreted to the
      outer face of the plasma membrane, they are covalently anchored in the wall
      through modified GPI anchors, with their binding domains elevated beyond the wall
      surface on highly glycosylated extended stalks. N-terminal globular domains bind
      peptide or sugar ligands, with between millimolar and nanomolar affinities. These
      affinities and the high density of adhesins and ligands at the cell surface
      determine microscopic and macroscopic characteristics of cell-cell associations.
      Central domains often include Thr-rich tandemly repeated sequences that are
      highly glycosylated. These domains potentiate cell-to-cell binding, but the
      molecular mechanism of such an association is not yet clear. These repeats also
      mediate recombination between repeats and between genes. The high levels of
      recombination and epigenetic regulation are sources of variation which enable the
      population to continually exploit new niches and resources.

PMID- 17554047
TI  - Sponge-associated microorganisms: evolution, ecology, and biotechnological
      potential.
AB  - Marine sponges often contain diverse and abundant microbial communities,
      including bacteria, archaea, microalgae, and fungi. In some cases, these
      microbial associates comprise as much as 40% of the sponge volume and can
      contribute significantly to host metabolism (e.g., via photosynthesis or nitrogen
      fixation). We review in detail the diversity of microbes associated with sponges,
      including extensive 16S rRNA-based phylogenetic analyses which support the
      previously suggested existence of a sponge-specific microbiota. These analyses
      provide a suitable vantage point from which to consider the potential
      evolutionary and ecological ramifications of these widespread, sponge-specific
      microorganisms. Subsequently, we examine the ecology of sponge-microbe
      associations, including the establishment and maintenance of these sometimes
      intimate partnerships, the varied nature of the interactions (ranging from
      mutualism to host-pathogen relationships), and the broad-scale patterns of
      symbiont distribution. The ecological and evolutionary importance of sponge
      microbe associations is mirrored by their enormous biotechnological potential:
      marine sponges are among the animal kingdom's most prolific producers of
      bioactive metabolites, and in at least some cases, the compounds are of microbial
      rather than sponge origin. We review the status of this important field,
      outlining the various approaches (e.g., cultivation, cell separation, and
      metagenomics) which have been employed to access the chemical wealth of sponge
      microbe associations.

PMID- 17554051
TI  - Approach to the infertile man.
AB  - INTRODUCTION: Infertility is one of commonest disorders to afflict young men and
      women. The evaluation of infertility is initiated typically after 1 yr of failure
      to conceive. DIAGNOSTIC EVALUATION: The couple should be evaluated together to
      determine whether the problem resides in the male partner, the female partner, or
      both. The objectives of evaluation are to exclude treatable conditions-
      gonadotropin deficiency, obstruction, and coital disorders--and identify those
      who are candidates for assisted reproductive technologies, those who are sterile
      and should consider adoption or artificial insemination using donor sperm, and
      those who should undergo genetic screening. All infertile men should undergo
      several semen analyses according to the World Health Organization manual, as well
      as measurements of testosterone, LH, and FSH levels. Hormone measurements can
      help determine whether the patient has gonadotropin deficiency (low testosterone
      and low or inappropriately normal LH and FSH), primary testicular failure (low
      testosterone, elevated LH and FSH), spermatogenic failure (normal testosterone
      and LH, elevated FSH), or androgen resistance (high testosterone, elevated LH). A
      majority of infertile men have normal testosterone, LH, and FSH levels.
      Obstruction should be ruled out in azoospermic men with normal testosterone, LH,
      and FSH levels. GENETICS: Yq microdeletions are the most prevalent cause of
      spermatogenic failure in men with azoospermia or severe oligozoospermia.
      Infertile men with azoospermia or severe oligozoospermia should undergo
      karyotyping and testing for Yq microdeletions. Men with congenital absence of vas
      should be tested for cystic fibrosis transmembrane conductance regulator
      mutations. THERAPY: Gonadotropin therapy is highly effective in gonadotropin
      deficient men. Intracytoplasmic sperm injection (ICSI) has emerged as the
      treatment of choice for idiopathic male factor infertility. However, ICSI is
      expensive and associated with a higher risk of multiple gestation, low birth
      weight, preterm delivery, perinatal complications, and chromosome aneuploidy than
      naturally conceived pregnancies. Men considering ICSI should be offered
      karyotyping, Yq microdeletion testing, and genetic counseling by counselors
      experienced in reproductive disorders.

PMID- 17554050
TI  - Viral proteomics.
AB  - Viruses have long been studied not only for their pathology and associated
      disease but also as model systems for molecular processes and as tools for
      identifying important cellular regulatory proteins and pathways. Recent advances
      in mass spectrometry methods coupled with the development of proteomic approaches
      have greatly facilitated the detection of virion components, protein interactions
      in infected cells, and virally induced changes in the cellular proteome,
      resulting in a more comprehensive understanding of viral infection. In addition,
      a rapidly increasing number of high-resolution structures for viral proteins have
      provided valuable information on the mechanism of action of these proteins as
      well as aided in the design and understanding of specific inhibitors that could
      be used in antiviral therapies. In this paper, we discuss proteomic studies
      conducted on all eukaryotic viruses and bacteriophages, covering virion
      composition, viral protein structures, virus-virus and virus-host protein
      interactions, and changes in the cellular proteome upon viral infection.

PMID- 17554052
TI  - Riedel's thyroiditis occurring in a multinodular goiter, mimicking thyroid
      cancer.

PMID- 17554053
TI  - Osteoporosis in children: still a diagnostic challenge.

PMID- 17554048
TI  - Environmental sensing and signal transduction pathways regulating
      morphopathogenic determinants of Candida albicans.
AB  - Candida albicans is an opportunistic fungal pathogen that is found in the normal
      gastrointestinal flora of most healthy humans. However, under certain
      environmental conditions, it can become a life-threatening pathogen. The shift
      from commensal organism to pathogen is often correlated with the capacity to
      undergo morphogenesis. Indeed, under certain conditions, including growth at
      ambient temperature, the presence of serum or N-acetylglucosamine, neutral pH,
      and nutrient starvation, C. albicans can undergo reversible transitions from the
      yeast form to the mycelial form. This morphological plasticity reflects the
      interplay of various signal transduction pathways, either stimulating or
      repressing hyphal formation. In this review, we provide an overview of the
      different sensing and signaling pathways involved in the morphogenesis and
      pathogenesis of C. albicans. Where appropriate, we compare the analogous
      pathways/genes in Saccharomyces cerevisiae in an attempt to highlight the
      evolution of the different components of the two organisms. The downstream
      components of these pathways, some of which may be interesting antifungal
      targets, are also discussed.

PMID- 17554049
TI  - Listeria monocytogenes surface proteins: from genome predictions to function.
AB  - The genome of the human food-borne pathogen Listeria monocytogenes is predicted
      to encode a high number of surface proteins. This abundance likely reflects the
      ability of this bacterium to survive in diverse environments, including soil,
      food, and the human host. This review focuses on the various mechanisms by which
      listerial proteins are attached at the bacterial surface and their many
      functions, including peptidoglycan metabolism, protein processing, adhesion to
      host cells, and invasion of host tissues. Extensive in silico analysis of the
      domains or motifs present in these mosaic proteins reveals that diverse
      structural features allow the surface proteome to interact with diverse bacterial
      or host components. This diversity offers new clues about the molecular bases of
      Listeria pathogenesis.

PMID- 17554054
TI  - Cardiovascular and cancer mortality after radioiodine treatment of
      hyperthyroidism.

PMID- 17554055
TI  - Does insulin resistance need resistin?

PMID- 17554056
TI  - Autoimmune hypophysitis: an underestimated disease in search of its
      autoantigen(s).

PMID- 17554057
TI  - Rapid generation of a functional NK-cell compartment.
AB  - Bone marrow transplants are an important therapeutic tool for treating certain
      types of cancer as well as genetic diseases affecting the hematopoietic system.
      Until the transferred stem cells differentiate and reconstitute the immune
      system, recipients are at increased risk from opportunistic infections. We report
      the rapid generation of a functional natural killer (NK) compartment in lethally
      irradiated mice that received bone marrow cells from a syngeneic donor by
      treatment with IL-2/anti-IL-2 antibody complexes. We demonstrate that IL-2
      complexes specifically expand the donor but not the host NK population and
      discuss the implications of this finding in the context of graft-versus-host
      disease and tumor relapse. Finally, we show that NK cells rapidly generated by IL
      2 complexes kill MHC class I-deficient cells effectively in vivo. These data
      underline the unique therapeutic potential of IL-2 complexes.

PMID- 17554058
TI  - Factor H mediated cell surface protection from complement is critical for the
      survival of PNH erythrocytes.
AB  - Paroxysmal nocturnal hemoglobinuria (PNH) cells are partially (type II) or
      completely (type III) deficient in GPI-linked complement regulatory proteins CD59
      and CD55. PNH III erythrocytes circulate 6 to 60 days in vivo. Why these cells
      are not lysed as rapidly by complement as unprotected foreign cells, which
      normally lyse within minutes, remains undetermined. Factor H plays a key role in
      the homeostasis of complement in fluid phase and on cell surfaces. We have
      recently shown that a recombinant protein encompassing the C-terminus of factor H
      (rH19-20) specifically blocks cell-surface complement regulatory functions of
      factor H without affecting fluid-phase control of complement. Here we show that
      PNH II and III cells become highly susceptible to complement-mediated lysis by
      nonacidified normal human serum in vitro, when the cell surface complement
      regulatory functions of factor H are blocked. The results indicate that cells
      deficient in surface-bound regulators are protected for extended periods of time
      by factor H.

PMID- 17554059
TI  - High-risk HLA allele mismatch combinations responsible for severe acute graft
      versus-host disease and implication for its molecular mechanism.
AB  - In allogenic hematopoietic stem-cell transplantation, an effect of HLA locus
      mismatch in allele level on clinical outcome has been clarified. However, the
      effect of each HLA allele mismatch combination is little known, and its molecular
      mechanism to induce acute graft-versus-host disease (aGVHD) remains to be
      elucidated. A total of 5210 donor-patient pairs who underwent transplantation
      through Japan Marrow Donor Program were analyzed. All HLA-A, -B, -C, -DRB1, 
      DQB1, and -DPB1 alleles were retrospectively typed in all pairs. The impacts of
      the HLA allele mismatch combinations and amino acid substitution positions in 6
      HLA loci on severe aGVHD were analyzed. A total of 15 significant high-risk HLA
      allele mismatch combinations and 1 HLA-DRB1-DQB1 linked mismatch combinations
      (high-risk mismatch) for severe aGVHD were identified, and the number of high
      risk mismatches was highly associated with the occurrence of severe aGVHD
      regardless of the presence of mismatch combinations other than high-risk
      mismatch. Furthermore, 6 specific amino acid substitution positions in HLA class
      I were identified as those responsible for severe aGVHD. These findings provide
      evidence to elucidate the mechanism of aGVHD on the basis of HLA molecule.
      Furthermore, the identification of high-risk mismatch, that is, nonpermissive
      mismatch, would be beneficial for the selection of a suitable donor.

PMID- 17554061
TI  - Point mutations involved in red cell stomatocytosis convert the electroneutral
      anion exchanger 1 to a nonselective cation conductance.
AB  - The anion exchanger 1 (AE1) is encoded by the SLC4A1 gene and catalyzes the
      electroneutral anion exchange across cell plasma membrane. It is the most
      abundant transmembrane protein expressed in red cell where it is involved in
      CO(2) transport. Recently, 4 new point mutations of SLC4A1 gene have been
      described leading to missense mutations in the protein sequence (L687P, D705Y,
      S731P, or H734R). These point mutations were associated with hemolytic anemia,
      and it was shown that they confer a cation transport feature to the human AE1.
      Facing this unexpected property for an electroneutral anion exchanger, we have
      studied the transport features of mutated hAE1 by expression in xenopus oocytes.
      Our results show that the point mutations of hAE1 convert the electroneutral
      anion exchanger to a cation conductance: the exchangers are no longer able to
      exchange Cl(-) and HCO(3)(-), whereas they transport Na(+) and K(+) through a
      conductive mechanism. These data shed new light on transport mechanisms showing
      the tiny difference, in terms of primary sequence, between an electroneutral
      exchange and a conductive pathway.

PMID- 17554060
TI  - Age-related defects in B lymphopoiesis underlie the myeloid dominance of adult
      leukemia.
AB  - Reduced lymphopoiesis during aging contributes to declines in immunity, but
      little consideration has been given to its effect on the development of
      hematologic disease. This report demonstrates that age-related defects in
      lymphopoiesis underlie the myeloid dominance of adult leukemia. Using a murine
      model of chronic myeloid leukemia, an adult-onset malignancy that arises from
      transformation of hematopoietic stem cells by the BCR-ABL(P210) oncogene, we
      demonstrate that young bone marrow (BM) cells that were transformed with BCR
      ABL(P210) initiated both a myeloproliferative disorder (MPD) and B-lymphoid
      leukemia, whereas BCR-ABL(P210)-transformed old BM cells recapitulated the human
      disease by inducing an MPD with rare lymphoid involvement. In addition, the
      lesser severity of MPDs initiated from old BCR-ABL(P210)-transduced BM cells
      revealed unappreciated defects in aged myeloid progenitors. These data
      demonstrate that aging affects patterns of leukemogenesis and indicate that the
      effects of senescence on hematopoiesis are more extensive than previously
      appreciated.

PMID- 17554062
TI  - Lipid rafts are required for Kit survival and proliferation signals.
AB  - In addition to its physiologic role as central regulator of the hematopoietic and
      reproductive systems, the Kit receptor tyrosine kinase (RTK) is pathologically
      overexpressed in some forms of leukemia and constitutively activated by oncogenic
      mutations in mast-cell proliferations and gastrointestinal stromal tumors. To
      gain insight into the general activation and signaling mechanisms of RTKs, we
      investigated the activation-dependent dynamic membrane distributions of wild-type
      and oncogenic forms of Kit in hematopoietic cells. Ligand-induced recruitment of
      wild-type Kit to lipid rafts after stimulation by Kit ligand (KL) and the
      constitutive localization of oncogenic Kit in lipid rafts are necessary for Kit
      mediated proliferation and survival signals. KL-dependent and oncogenic Kit
      kinase activity resulted in recruitment of the regulatory phosphatidylinositol 3
      kinase (PI3-K) subunit p85 to rafts where the catalytical PI3-K subunit p110
      constitutively resides. Cholesterol depletion by methyl-beta-cyclodextrin
      prevented Kit-mediated activation of the PI3-K downstream target Akt and
      inhibited cellular proliferation by KL-activated or oncogenic Kit, including
      mutants resistant to the Kit inhibitor imatinib-mesylate. Our data are consistent
      with the notion that Kit recruitment to lipid rafts is required for efficient
      activation of the PI3-K/Akt pathway and Kit-mediated proliferation.

PMID- 17554064
TI  - Vitamins and Thrombosis (VITRO) study--homocysteine lowering with B vitamins.

PMID- 17554063
TI  - Direct interaction between Kit and the interleukin-7 receptor.
AB  - In vivo analyses of thymopoiesis in mice defective in signaling through Kit and
      gammac or Kit and IL-7Ralpha demonstrate synergy and partial complementation of
      gammac or IL-7-mediated signaling by the Kit signaling pathway. Our molecular
      analysis in T-lymphoid cells as well as in nonhematopoietic cells shows that Kit
      and IL-7R signaling pathways directly interact. KL-mediated activation of Kit
      induced strong tyrosine phosphorylation of gammac and IL-7Ralpha in the absence
      of IL-7. Activated Kit formed a complex with either IL-7Ralpha or gammac, and
      tyrosine phosphorylation of both subunits occurred independently of Jak3,
      suggesting that gammac and IL-7Ralpha are each direct substrates of Kit. Kit
      activated Jak3 in an IL-7R-dependent manner. Moreover, deficient Stat5 activation
      of the Kit mutant YY567/569FF lacking intrinsic Src activation capacity was
      partially reconstituted in the presence of IL-7R and Jak3. Based on the molecular
      data, we propose a model of Kit-mediated functional activation of gammac
      containing receptors such as IL-7R, similar to the interaction between Kit and
      Epo-R. Such indirect activation of the Jak-Stat pathway induced by the
      interaction between an RTK and type I cytokine receptor could be the underlying
      mechanism for a context-specific signaling repertoire of a pleiotropic RTK-like
      Kit.

PMID- 17554065
TI  - Vitamin supplementation in the secondary prevention of venous thromboembolism:
      about the VITRO study.

PMID- 17554067
TI  - RAG1 and BRCA2 polymorphisms in non-Hodgkin lymphoma.

PMID- 17554069
TI  - Targeting host B-cell immune responses by persistent donor NK-cell alloreactivity
      following nonmyeloablative allogeneic stem cell transplantation.

PMID- 17554070
TI  - Effect of the new HJV-L165X mutation on penetrance of HFE.

PMID- 17554071
TI  - A closer look at intravascular hemolysis (IVH) following intravenous anti-D for
      immune thrombocytopenic purpura (ITP).

PMID- 17554073
TI  - Specific down-regulation of connective tissue growth factor attenuates
      progression of nephropathy in mouse models of type 1 and type 2 diabetes.
AB  - Diabetic nephropathy (DN) remains a major complication in both type 1 and type 2
      diabetes. Systemic administration of antitransforming growth factor-beta (TGF
      beta) antibody has shown some promise in mouse models of DN. However, chronic
      blockade of the multifunctional TGB-beta could be problematic. Several downstream
      effects of TGF-beta are mediated by connective tissue growth factor (CTGF), which
      is up-regulated in several renal cells and secreted in the urine in the diabetic
      state. Using murine models of DN (type 1 and type 2) and a CTGF antisense
      oligonucleotide (ASO) of novel chimeric chemistry, we evaluated the specific role
      of this target in DN. In the type 1 model of DN, C57BL6 mice were made diabetic
      using streptozotocin injections and hyperglycemic animals were treated with CTGF
      ASOs (20 mg/kg/2 qw) for 4 months. ASO, but not mismatch control oligonucleotide,
      -treated animals showed significant reduction in target CTGF expression in the
      kidney with a concomitant decrease in proteinuria and albuminuria. Treatment with
      the CTGF ASO for 8 wk reduced serum creatinine and attenuated urinary albuminuria
      and proteinuria in diabetic db/db mice, a model of type 2 DN. The ASO also
      reduced expression of genes involved in matrix expansion such as fibronectin and
      collagen (I and IV) and an inhibitor of matrix degradation, PAI-1, in the renal
      cortex, contributing to significant reversal of mesangial expansion in both
      models of DN. Pathway analyses demonstrated that diabetes-induced phosphorylation
      of p38 MAPK and its downstream target CREB was also inhibited by the ASO. Our
      results strongly suggest that blocking CTGF using a chimeric ASO holds
      substantial promise for the treatment of DN.

PMID- 17554074
TI  - Re: age-related brain cholinesterase inhibition kinetics following in vitro
      incubation with chlorpyrifos-oxon and diazinon-oxon.

PMID- 17554075
TI  - Ab initio modeling of glycosyl torsions and anomeric effects in a model
      carbohydrate: 2-ethoxy tetrahydropyran.
AB  - A range of ab initio calculations were carried out on the axial and equatorial
      anomers of the model carbohydrate 2-ethoxy tetrahydropyran to evaluate the level
      of theory required to accurately evaluate the glycosyl dihedral angle and the
      anomeric ratio. Vacuum CCSD(T)/CBS extrapolations at the global minimum yield
      DeltaE = E(equatorial) - E(axial) = 1.42 kcal/mol. When corrected for solvent (by
      the IEFPCM model), zero-point vibrations and entropy, DeltaG(298) = 0.49
      kcal/mol, in excellent agreement with the experimental value of 0.47 +/- 0.3
      kcal/mol. A new additivity scheme, the layered composite method (LCM), yields
      DeltaE to within 0.1 kcal/mol of the CCSD(T)/CBS result at a fraction of the
      computer requirements. Anomeric ratios and one-dimensional torsional surfaces
      generated by LCM and the even more efficient MP2/cc-pVTZ level of theory are in
      excellent agreement, indicating that the latter is suitable for force-field
      parameterization of carbohydrates. Hartree-Fock and density functional theory
      differ from CCSD(T)/CBS for DeltaE by approximately 1 kcal/mol; they show similar
      deviations in torsional surfaces evaluated from LCM. A comparison of vacuum and
      solvent-corrected one- and two-dimensional torsional surfaces indicates the
      equatorial form of 2-ethoxy tetrahydropyran is more sensitive to solvent than the
      axial.

PMID- 17554076
TI  - Dysferlin is expressed in human placenta but does not associate with caveolin.
AB  - A proteomics screen of human placental microvillous syncytiotrophoblasts (STBs)
      revealed the expression of dysferlin (DYSF), a plasma membrane repair protein
      associated with certain muscular dystrophies. This was unexpected given that
      previous studies of DYSF have been restricted to skeletal muscle. Within the
      placenta, DYSF localized to the STB and, with the exception of variable labeling
      in the fetal placental endothelium, none of the other cell types expressed
      detectable levels of DYSF. Such restricted expression was recapitulated using
      primary trophoblast cell cultures, because the syncytia expressed DYSF, but not
      the prefusion mononuclear cells. The apical plasma membrane of the STB contained
      approximately 4-fold more DYSF than the basal membrane, suggesting polarized
      trafficking. Unlike skeletal muscle, DYSF in the STB is localized to the plasma
      membrane in the absence of caveolin. DYSF expression in the STB was
      developmentally regulated, because first-trimester placentas expressed
      approximately 3-fold more DYSF than term placentas. As the current literature
      indicates that few cell types express DYSF, it is of interest that the two major
      syncytial structures in the human body, skeletal muscle and the STB, express this
      protein.

PMID- 17554077
TI  - Expression of endothelin 1 and its receptors in the hypoxic pregnant rat.
AB  - Endothelin 1 (EDN1) plays a primary role in the pathophysiology of hypoxia
      induced fetal growth restriction in the rat. In this study we evaluated the
      effects of chronic maternal hypoxia on the expression of endothelin and its
      receptors and on receptor binding activity in the uterus and placenta of the rat,
      in order to elucidate their roles in hypoxia-induced fetal growth restriction.
      Timed-pregnant Sprague-Dawley rats were maintained in either a normoxic or a
      normobaric hypoxic (12% O(2)) atmosphere from Gestational Days 18-21. Uterine and
      placental tissues collected on Gestational Day 21 were assayed for Edn1, Ednra,
      and Ednrb (endothelin receptors) mRNA expression by real-time quantitative RT
      PCR, for localization of EDN1 and its receptors by immunohistochemistry, for
      EDNRA and EDNRB protein expression by Western blot, and for receptor binding
      activity by homologous competitive binding assays. EDN1 mRNA expression was
      significantly increased in the hypoxic placenta, but not in the uterus, compared
      with normoxic controls. Immunohistochemistry revealed increased EDN1 specifically
      in the labyrinth of the placenta. Receptor mRNA levels were not significantly
      affected by hypoxia, but EDNRA protein expression was significantly decreased
      specifically in the uterine placental beds. Receptor binding decreased
      significantly in response to hypoxia in all tissues investigated, compared with
      controls. These results suggest that chronic maternal hypoxia results in
      increased expression of EDN1 in the placenta but not in the uterus, and that
      reduced binding activity, rather than regulation of receptor expression, is a
      mechanism by which these tissues regulate the local hemodynamic response to
      increased endogenous placental EDN1 in the setting of hypoxia.

PMID- 17554078
TI  - Negative effect of estradiol on luteinizing hormone throughout the ovulatory
      luteinizing hormone surge in mares.
AB  - The negative effect of estradiol-17beta (E2) on LH, based on exogenous E2
      treatments, and the reciprocal effect of LH on endogenous E2, based on hCG
      treatments, were studied throughout the ovulatory follicular wave during a total
      of 103 equine estrous cycles in seven experiments. An initial study developed E2
      treatment protocols that approximated physiologic E2 concentrations during the
      estrous cycle. On Day 13 (ovulation = Day 0), when basal concentrations of E2 and
      LH precede the ovulatory surges, exogenous E2 significantly depressed LH
      concentrations to below basal levels. Ablation of all follicles > or = 10 mm when
      the largest was > or =20 mm resulted in an increase in percentage change in LH
      concentration within 8 h that was greater (P < 0.03) than for controls or E2
      treated/follicle-ablated mares. Significant decreases in LH occurred when E2 was
      given when the largest follicle was either > or =25 mm, > or =28 mm, > or =35 mm,
      or near ovulation. Treatment with 200 or 2000 IU of hCG did not affect E2
      concentrations during the initial portion of the LH surge (largest follicle, > or
      =25 mm), but 2000 IU significantly depressed E2 concentrations before ovulation
      (largest follicle, > or =35 mm). Results indicated a continuous negative effect
      of E2 on LH throughout the ovulatory follicular wave and may be related to the
      long LH surge and the long follicular phase in mares. Results also indicated that
      a reciprocal negative effect of LH on E2 does not develop until the E2 surge
      reaches a peak.

PMID- 17554079
TI  - High transcript level of fatty acid-binding protein 11 but not of very low
      density lipoprotein receptor is correlated to ovarian follicle atresia in a
      teleost fish (Solea senegalensis).
AB  - Transcripts encoding a fatty acid-binding protein (FABP), Fabp11, and two
      isoforms of very low-density lipoprotein receptor (Vldlr; vitellogenin receptor)
      were characterized from the ovary of Senegalese sole (Solea senegalensis).
      Phylogenetic analyses of vertebrate FABPs demonstrated that Senegalese sole
      Fabp11, as zebrafish (Danio rerio) homologous sequences, is part of a newly
      defined teleost fish FABP subfamily that is a sister clade of tetrapod
      FABP4/FABP5/FABP8/FABP9. RT-PCR revealed high levels of vldlr transcript splicing
      variants in the ovaries and, to a lesser extent, in somatic tissues, whereas
      fabp11 was highly expressed in the ovaries, liver, and adipose tissue. In situ
      hybridization analysis showed vldlr and fabp11 mRNAs in previtellogenic oocytes,
      whereas no hybridization signals were detected in the larger vitellogenic
      oocytes. Transcript expression of fabp11 was strongly upregulated in somatic
      cells surrounding atretic follicles. Real-time quantitative RT-PCR demonstrated
      that ovarian transcript levels of vldlr and fabp11 had a significant positive
      correlation with the percentage of follicles in previtellogenesis and atresia,
      respectively. These results suggest that the expression level of vldlr
      transcripts may be used as a precocious functional marker to quantify the number
      of oocytes recruited for vitellogenesis and that fabp11 mRNA may be a very useful
      molecular marker for determining cellular events and environmental factors that
      regulate follicular atresia in fish.

PMID- 17554080
TI  - CATSPER channel-mediated Ca2+ entry into mouse sperm triggers a tail-to-head
      propagation.
AB  - Many Ca(2+) channel proteins have been detected in mammalian sperm, but only the
      four CATSPER channels have been clearly shown to be required for male fertility.
      Ca(2+) entry through the principal piece-localized CATSPER channels has been
      implicated in the activation of hyperactivated motility. In the present study, we
      show that the Ca(2+) entry also triggers a tail-to-head Ca(2+) propagation in the
      mouse sperm. When activated with 8-Br-cAMP, 8-Br-cGMP, or alkaline
      depolarization, a CATSPER-dependent increase in intracellular Ca(2+)
      concentration starts in the principal piece, propagates through the midpiece, and
      reaches the head in a few seconds. The Ca(2+) propagation through the midpiece
      leads to a Ca(2+)-dependent increase in NADH fluorescence. In addition, CatSper1
      mutant sperm have lower intracellular ATP levels than wild-type sperm. Thus, a
      Ca(2+) influx in the principal piece through CATSPER channels can not only
      initiate hyperactivated motility, but can also trigger a tail-to-head Ca(2+)
      propagation that leads to an increase in [NADH] and may regulate ATP homeostasis.

PMID- 17554081
TI  - Neutral mitochondrial heteroplasmy alters physiological function in mice.
AB  - Cytoplasmic transfer is an assisted reproductive technique that involves the
      infusion of ooplasm from a donor oocyte into a recipient oocyte of inferior
      developmental competence. Although this technique has shown some success for
      couples with recurrent in vitro fertilization failure, it results in
      mitochondrial heteroplasmy in the offspring, defined as the presence of two
      different mitochondrial genomes in the same individual. Because the long-term
      health consequences of mitochondrial heteroplasmy are unknown, there is a need
      for appropriate animal models to evaluate any physiological changes of dual mtDNA
      genotypes. This longitudinal study was designed as a preliminary screen of basic
      physiological functions for heteroplasmic mice (NZB mtDNA on a BALB/cByJ
      background). The mice were tested for cardiovascular and metabolic function,
      hematological parameters, body mass analysis, ovarian reserve, and tissue
      histologic abnormalities over a period of 15 mo. Heteroplasmic mice developed
      systemic hypertension that corrected over time and was accompanied by cardiac
      changes consistent with pulmonary hypertension. In addition, heteroplasmic
      animals had increased body mass and fat mass compared with controls at all ages.
      Finally, these animals had abnormalities in electrolytes and hematological
      parameters. Our findings suggest that there are significant physiological
      differences between heteroplasmic and control mice. Because ooplasm transfer
      appears to be consistently associated with mitochondrial heteroplasmy, children
      conceived through ooplasm transfer should be closely followed to determine if
      they are at risk for any health problems.

PMID- 17554082
TI  - Induction of apoptosis by 9,10-dimethyl-1,2-benzanthracene in cultured
      preovulatory rat follicles is preceded by a rise in reactive oxygen species and
      is prevented by glutathione.
AB  - The polycyclic aromatic hydrocarbon (PAH) 9,10-dimethyl-1,2-benzanthracene (DMBA)
      destroys primordial, primary, and secondary ovarian follicles in rodents, but its
      effects on antral follicles have received limited attention. PAHs are metabolized
      to reactive species, some of which can undergo redox cycling to generate reactive
      oxygen species (ROS). We previously showed that ROS initiate apoptosis in
      preovulatory follicles cultured without gonadotropin support and that glutathione
      (GSH) depletion induces apoptosis in the presence of gonadotropins. In the
      present study, we tested the hypothesis that DMBA induces apoptosis in
      preovulatory follicles, which is mediated by ROS and prevented by GSH.
      Preovulatory follicles were isolated from ovaries of 25-day-old rats 48 h after
      the injection of 10 IU of eCG and were cultured with DMBA in the presence of FSH
      for 2 to 48 h. DMBA induced granulosa cell (GC) and theca cell (TC) apoptosis at
      48 h, as judged by TUNEL and activated caspase-3 immunostaining. DMBA treatment
      also increased the numbers of GCs and TCs that immunostained for the proapoptotic
      protein BAX. Follicular ROS levels were significantly increased in DMBA-treated
      follicles at 12, 24, and 48 h. GSH supplementation protected against and GSH
      depletion enhanced the induction of apoptosis in GCs and TCs by DMBA. These
      findings suggest that GSH is a critical protective mechanism against DMBA-induced
      apoptosis in antral follicles and that ROS generation may mediate DMBA-induced GC
      apoptosis.

PMID- 17554083
TI  - Involvement of protein kinase B/AKT in early development of mouse fertilized
      eggs.
AB  - The activation of AKT (also called protein kinase B) is thought to be a critical
      step in the phosphoinositide 3-kinase pathway that regulates cell growth and
      differentiation. In this report, we investigated the role of AKT in the
      regulation of mouse early embryo development. Injection of mRNA coding for a
      constitutively active myristoylated AKT (myr-Akt1) into one-cell stage fertilized
      eggs induced cell division more effectively than injection of wild-type AKT (Akt1
      WT) mRNA, whereas microinjection of mRNA of kinase-deficient AKT (Akt1-KD)
      delayed the first mitotic division. Meanwhile, microinjection of different kinds
      of mRNA of AKT affected the phosphorylation status of CDC2A-Tyr15 and the
      activation of M-phase promoting factor (MPF). To investigate the intermediate
      factor between AKT and MPF, we then injected one-cell stage eggs first with Akt1
      WT mRNA or myr-Akt1 mRNA and then with mRNA encoding either wild-type CDC25B
      (Cdc25b-WT) or a AKT-nonphosphorylatable Ser351 to Ala CDC25B mutant (Cdc25b
      S351A). Cdc25b-S351A strongly inhibited the effect of AKT. Therefore, AKT causes
      the activation of MPF and strongly promotes the development of one-cell stage
      mouse fertilized eggs by inducing AKT-dependent phosphorylation of CDC25B, a
      member of the CDC25 phosphatase family. Our finding that CDC25B acts as a
      potential target of AKT provides new insight into the effect of AKT in the
      regulation of early development of mouse embryos.

PMID- 17554084
TI  - Cerebral asymmetries in sleep-dependent processes of memory consolidation.
AB  - Preference for previously seen, unfamiliar objects reflects a memory bias on
      affective judgment, known as the "mere exposure effect" (MEE). Here, we
      investigated the effect of time, post-exposure sleep, and the brain hemisphere
      solicited on preference generalization toward objects viewed in different
      perspectives. When presented in the right visual field (RVF), which promotes
      preferential processing in the left hemisphere, same and mirrored exemplars were
      preferred immediately after exposure. MEE generalized to much dissimilar views
      after three nights of sleep. Conversely, object presentation in the left visual
      field (LVF), promoting right hemisphere processing, elicited a MEE for same views
      immediately after exposure, then for mirror views after sleep. Most importantly,
      sleep deprivation during the first post-exposure night, although followed by two
      recovery nights, extinguished MEE for all views in the LVF but not in the RVF.
      Besides demonstrating that post-exposure time and sleep facilitate the
      generalization process by which we integrate various representations of an
      object, our results suggest that mostly in the right hemisphere, sleep may be
      mandatory to consolidate the memory bias underlying affective preference. These
      interhemispheric differences tentatively call for a reappraisal of the role of
      cerebral asymmetries in wake- and sleep-dependent processes of memory
      consolidation.

PMID- 17554086
TI  - Remodeling of hippocampal mossy fibers is selectively induced seven days after
      the acquisition of a spatial but not a cued reference memory task.
AB  - Relating storage of specific information to a particular neuromorphological
      change is difficult because behavioral performance factors are not readily
      disambiguated from underlying cognitive processes. This issue is addressed here
      by demonstrating robust reorganization of the hippocampal mossy fiber terminal
      field (MFTF) when adult rats learn the location of a hidden platform but not when
      rats learn to locate a visible platform. Because the latter task requires
      essentially the same behavioral performance as the former, the observed MFTF
      growth is seen as the consequence of specific input-dependent hippocampal
      activity patterns selectively generated by processing of extramaze but not
      intramaze cues. Successful performance on the hidden platform task requires
      formation of spatial memory. Increased MFTFs in hidden platform-trained rats are
      observed 7 d but not 2 d after training nor in swim controls. These results
      suggest that structural plasticity of the mossy fiber:CA3 circuit may contribute
      to the maintenance of long-lasting memory but not to the initial storage of the
      spatial context.

PMID- 17554085
TI  - GAP-43 gene expression regulates information storage.
AB  - Previous reports have shown that overexpression of the growth- and plasticity
      associated protein GAP-43 improves memory. However, the relation between the
      levels of this protein to memory enhancement remains unknown. Here, we studied
      this issue in transgenic mice (G-Phos) overexpressing native, chick GAP-43. These
      G-Phos mice could be divided at the behavioral level into "spatial bright" and
      "spatial dull" groups based on their performance on two hidden platform water
      maze tasks. G-Phos dull mice showed both acquisition and retention deficits on
      the fixed hidden platform task, but were able to learn a visible platform task. G
      Phos bright mice showed memory enhancement relative to wild type on the more
      difficult movable hidden platform spatial memory task. In the hippocampus, the G
      Phos dull group showed a 50% greater transgenic GAP-43 protein level and a
      twofold elevated transgenic GAP-43 mRNA level than that measured in the G-Phos
      bright group. Unexpectedly, the dull group also showed an 80% reduction in
      hippocampal Tau1 staining. The high levels of GAP-43 seen here leading to memory
      impairment find its histochemical and behavioral parallel in the observation of
      Rekart et al. (Neuroscience 126: 579-584) who described elevated levels of GAP-43
      protein in the hippocampus of Alzheimer's patients. The present data suggest that
      moderate overexpression of a phosphorylatable plasticity-related protein can
      enhance memory, while excessive overexpression may produce a "neuroplasticity
      burden" leading to degenerative and hypertrophic events culminating in memory
      dysfunction.

PMID- 17554087
TI  - Dissociated roles for the lateral and medial septum in elemental and contextual
      fear conditioning.
AB  - Extensive evidence indicates that the septum plays a predominant role in fear
      learning, yet the direction of this control is still a matter of debate.
      Increasing data suggest that the medial (MS) and lateral septum (LS) would be
      differentially required in fear conditioning depending on whether a discrete
      conditional stimulus (CS) predicts, or not, the occurrence of an aversive
      unconditional stimulus (US). Here, using a tone CS-US pairing (predictive
      discrete CS, context in background) or unpairing (context in foreground)
      conditioning procedure, we show, in mice, that pretraining inactivation of the LS
      totally disrupted tone fear conditioning, which, otherwise, was spared by
      inactivation of the MS. Inactivating the LS also reduced foreground contextual
      fear conditioning, while sparing the higher level of conditioned freezing to the
      foreground (CS-US unpairing) than to the background context (CS-US pairing). In
      contrast, inactivation of the MS totally abolished this training-dependent level
      of contextual freezing. Interestingly, inactivation of the MS enhanced background
      contextual conditioning under the pairing condition, whereas it reduced
      foreground contextual conditioning under the unpairing condition. Hence, the
      present findings reveal a functional dissociation between the LS and the MS in
      Pavlovian fear conditioning depending on the predictive value of the discrete CS.
      While the requirement of the LS is crucial for the appropriate processing of the
      tone CS-US association, the MS is crucial for an appropriate processing of
      contextual cues as foreground or background information.

PMID- 17554088
TI  - Forgetting of stimulus attributes: some implications for hippocampal models of
      memory.

PMID- 17554089
TI  - Incorporating leadership knowledge and skills into the dental education
      community.
AB  - Leadership has been studied for the past four decades with an emphasis upon
      leadership and the transformation of various cultures, especially within the
      private sector. It is also becoming evident that leaders and leadership skills
      are often derived from core personal values and perceptions of what is and what
      could be. This summary describes an eleven-week selective course termed "Dean's
      Leadership Course" at the School of Dentistry at the University of Southern
      California. This selective course (a non-credit elective learning opportunity
      outside the formal curriculum) recruits a modest team of learners consisting of
      faculty, staff, and students and approaches leadership within the context of a
      "learning organization" coupled with case-based and problem-based learning. At
      the conclusion of this eleven-week course, participants are granted continuing
      education credit. This summary encourages others in dental education to consider
      the compelling opportunity to nurture and cultivate leadership within the
      university dental school environs.

PMID- 17554090
TI  - Does the dental school work environment promote successful academic careers?
AB  - A consistent theme in the national dialogue about future directions for the
      educational arm of dentistry is how best to cultivate a school environment that
      will be seen as attractive by members of the dental community who desire to serve
      their profession as teachers and scholars. As a first step toward stimulating
      broad-based reflection on the working environment within dental schools, the ADEA
      Commission on Change and Innovation (CCI) conducted a symposium titled "Change,
      Innovation, and the Quality of Faculty Work-Life" at the 2007 ADEA Annual Session
      in New Orleans. Aspects of this article are based on the content of this
      symposium, which explored research on the perceptions and concerns of dental
      faculty regarding the current academic workplace and provided perspectives of
      university faculty about university life and career growth. This article reviews
      the findings from two interview-based qualitative assessments of faculty
      perceptions of work-life in dental schools and other schools of higher education,
      presents a preliminary summary of the first national survey of dental school
      faculty regarding their impressions of the academic work environment, and makes
      recommendations for enhancing the dental school work environment with an emphasis
      on those factors that influence career growth. Results from these three studies
      illustrate faculty perceptions about the promotion and tenure and performance
      evaluation processes; workload and quality of work-life; and quality of
      institutional support.

PMID- 17554091
TI  - Patient preference for a racially or gender-concordant student dentist.
AB  - Disparities in health and health care due to race and ethnicity are a national
      problem. One commonly proposed method to address disparities is to increase the
      number of underrepresented minorities in the health professions to serve the
      needs of growing minority populations. This position is based in part on the
      racial concordance hypothesis, an untested assumption that minority patients
      prefer to be treated by providers of the same race as themselves. The purpose of
      this study was to test the racial concordance hypothesis. Gender preference of
      dental patients was also investigated. One hundred twenty male and female
      Caucasian, African American, Hispanic, and Asian dental patients over eighteen
      were recruited from the reception area of a private dental school clinic in
      Northern California. Participants were randomly assigned to a treatment condition
      that gave them a choice between two equally qualified fictitious dental students
      that varied on race and gender. Participants were initially blinded to the
      study's purpose to preserve the authenticity of the choice decision. Results
      showed that 58 percent of the participants had no preference for the race or
      gender of their student dentist, but that some black and Hispanic patients
      preferred a racially concordant student dentist and some female patients
      preferred a gender-concordant student dentist. Hispanic females were especially
      likely to prefer racial and gender concordance. The findings suggest that the
      racial concordance hypothesis may not apply to choosing a dentist and thus may
      not be as strong an argument to justify efforts to increase diversity in dental
      schools as previously thought.

PMID- 17554092
TI  - Clinical quality assurance surveillance and targeted interventions: managing
      unfavorable trends in a dental school clinic.
AB  - Dental schools establish quality assurance (QA) programs that are intended to
      improve patient care, comply with requirements of liability carriers and
      regulatory agencies, and maintain accreditation. Data collection, trend analysis,
      and interventions are typically used in QA programs to monitor and improve
      compliance. The purpose of this article is to discuss unfavorable trends and
      examine the effect of targeted interventions in three clinical operations:
      infection control, removable prosthodontics, and case reviews of students'
      patient care in progress (interim case reviews) at a U.S. dental school.
      Infection control compliance was evaluated and interventions were implemented
      beginning in 2002 to correct unfavorable trends in two protocols: placement of
      students' mobile supply cart and the use of overgloves. A predelivery esthetic
      consent was introduced in spring 2004 to decrease esthetic failures in removable
      prosthodontics. For interim case reviews, two areas received interventions going
      back to 2003: reevaluation following initial periodontal therapy and orthodontic
      screening. The data presented are not meant to show conclusive success of
      particular interventions, but to display broad trends and suggest methods to
      manage quality assurance parameters. These trends suggest we had better success
      with the interventions that were simple, valuable, measurable, and repeatable
      than with interventions that less fit these criteria.

PMID- 17554093
TI  - Expert performance on a virtual reality simulation system.
AB  - The objective of this research was to determine if the essence of expert
      performance could be captured on a virtual reality simulation system. Six experts
      in operative dentistry, six experts in periodontology, and six novice dental
      students performed a Class II tooth preparation task on the lower left second
      premolar. All subjects performed a pre-test to assess the basic skill level of
      each group. During the (limited) training component of the study, the three
      groups practiced three tooth preparations and received augmented feedback. At
      both a one-minute and one-day interval, subjects performed a final test in the
      absence of augmented feedback. All preparations were graded by the simulation
      system. The results showed at pre-test a significantly better performance of the
      experts in operative dentistry as compared to the novices. During the practice
      (acquisition) phase, the experts in operative dentistry outperformed both the
      periodontologists and novices, whereas the experts in periodontology performed
      more accurately than the novices. After one minute and one day following
      practice, similar results were obtained. Retention performance was most accurate
      after a one-day delay. Based on these results, the simulator appears to be a
      valid and reliable tool to capture expert performance. It is an effective
      screening device for assessing the level of expert performance.

PMID- 17554094
TI  - Management of high caries risk and high caries activity patients: rampant caries
      control program (RCCP).
AB  - The purpose of this article is to describe the Rampant Caries Control Program
      established in the operative dentistry third-year clinic at the University of
      Iowa College of Dentistry. This program represents a new approach to the
      management of high caries risk and high caries activity patients who come to the
      school. The patients are referred initially to the third-year operative clinic
      only for disease control (phase I) to help them decrease the caries risk and
      activity. The disease control phase has three important components: 1) caries
      risk assessment evaluation and reevaluation throughout their treatment, in which
      individual risk factors are identified and recommendations are made; 2) caries
      removal and placement of transitional restorations using fluoride release
      restorative materials (glass ionomers); and 3) chemotherapeutic agents and
      preventive treatment in which a therapeutic regimen for prevention and
      nonsurgical treatment is established according to each patient's individual risk
      factors. About 50 percent of patients have dropped from the program, 36 percent
      currently are under disease control treatment, and 14 percent have finished the
      disease control phase of the program. After the disease is controlled through
      modification of risk factors and activity, the patients can be referred for
      reevaluation prior to beginning the rehabilitation phase.

PMID- 17554095
TI  - Evolution of a tobacco cessation curriculum for dental hygiene students at
      Indiana University School of Dentistry.
AB  - Barriers to consistent implementation of tobacco cessation strategies by dental
      hygiene students in practice may be overcome through mentoring by expert faculty
      members. This article describes a pilot study using an innovative method to
      achieve higher levels of student-perceived confidence and skill in delivering
      cessation messages to patients. Following completion of the didactic course
      content, each student selected a tobacco user to complete the Indiana University
      Nicotine Dependence Program Patient Assessment Questionnaire (PAQ). Detailed
      analysis of the questionnaire and development of specific cessation strategies
      were accomplished in a one-to-one interchange with expert faculty members.
      Students provided suggestions to patients, wrote papers summarizing their
      experiences, and were asked to complete an anonymous survey. Forty-four of forty
      six students completed the survey. Eighty percent reported the mentored session
      was useful in learning specific cessation strategies; 83 percent reported the
      session helped to boost their confidence levels in approaching patients in
      tobacco cessation; 83 percent believed they would use learned strategies with
      other patients; and 86 percent recommended this educational approach for future
      students. Additional mentoring may overcome barriers to approaching patients in
      tobacco cessation by increasing levels of confidence and skill when delivering
      cessation messages. This may translate into continued application of these
      strategies in private practice, resulting in potential benefits to the health of
      the public.

PMID- 17554096
TI  - Preparation course for Part I of the National Dental Boards: lessons learned.
AB  - Student performance on national board examinations is the predominant litmus test
      for successful programs in health science education. Many different strategies
      have been used to increase passing rates among students. The objectives of this
      study were to investigate the influence of a voluntary eighteen-hour National
      Board Dental Examination Part I (NBDE Part I) preparation course on student
      performance on the NBDE Part I and to assess students' perspectives on the
      preparation course. Students' perspectives were obtained through a questionnaire
      and focus groups. There were significant associations between the students' GPA
      and the overall examination score and between the course grades corresponding
      with each section and the section scores. Students attending sessions devoted to
      specific NBDE subject areas did not obtain significantly better scores for that
      subject area than nonattending students. Also, the students did not obtain
      significantly better overall scores for NBDE Part I than in previous years when a
      preparation course was not conducted. Students most frequently rated the Dental
      Deck's NBDE Part I Cards as the most helpful study aid, followed by old NBDE Part
      I tests. The most frequent student rating for most of the presentations was
      "somewhat helpful," while the most frequent rating for resources placed on
      Blackboard such as tables and summary material was "helpful." Based upon the
      findings, we recommended discontinuation of the classroom presentation portion of
      the board preparation course.

PMID- 17554097
TI  - The relationship between gender and postgraduate aspirations among first- and
      fourth-year students at public dental schools: a longitudinal analysis.
AB  - The purpose of this study was to examine gender differences and other predictors
      of postgraduate plans among U.S. dental students. A national sample of dental
      students was surveyed in their first and fourth years of dental school. Female
      first-year students were less likely than male students to express interest in
      specialization in endodontics and oral surgery. Fourth-year students who had a
      dental school mentor, a high GPA, and encouragement from significant others were
      more likely to apply for postgraduate training. Gender and first-year interest in
      dental specialization did not affect the likelihood of applying for postgraduate
      training in the fourth year. Female fourth-year students were more likely to
      predict that they would be an associate in a practice five years following
      graduation. The results suggest that mentoring and faculty encouragement are
      important influences on dental students' plans for postgraduate education.

PMID- 17554098
TI  - Effect of school environment on dental students' perceptions of cultural
      competency curricula and preparedness to care for diverse populations.
AB  - Reports of oral health disparities among racial, ethnic, and socioeconomic
      sectors of the U.S. population have hastened development of strategies to address
      this issue. Among these strategies is revising dental school curricula in order
      to develop more culturally competent graduates. The present study uses data from
      the 2003 American Dental Education Association (ADEA) survey of dental school
      seniors to assess students' perceptions of the adequacy of their cultural
      competency training. We hypothesize that these perceptions are influenced by
      multiple student characteristics and contextual factors, including a school's
      status with respect to the Pipeline, Professions, and Practice initiative of the
      Robert Wood Johnson Foundation and The California Endowment. Response data from
      ADEA survey items reflecting student perceptions of adequacy of curriculum time
      devoted to cultural competency and their preparedness to treat an ethnically and
      culturally diverse population were analyzed to assess the influence of selected
      student and contextual factors. Student gender, marital status, and level of
      educational debt were found to influence the curriculum time variable, and
      students at California schools reported higher perceived preparedness levels than
      students at dental schools nationwide. Dental school environments promoting
      acceptance and respect of diverse ethnicities/cultures and student race/ethnicity
      were significantly associated with students' perception of the adequacy of
      curriculum time for cultural competency and students' perception of their
      preparedness to provide oral health care for racially and culturally diverse
      groups. The findings provide insight for development of cultural competency
      curricula and direction for future study in this area.

PMID- 17554099
TI  - Do tutor expertise and experience influence student performance in a problem
      based curriculum?
AB  - The purpose of this study was to evaluate the association between student
      performance and tutor expertise and experience in the Restorative Treatment
      course in a problem-based learning (PBL) dental curriculum. This retrospective
      study evaluated a cohort of 206 third-year dental students at Harvard School of
      Dental Medicine who were enrolled in the Restorative Treatment course between
      2000 and 2005. Tutor expertise in prosthodontics and prior tutoring experience
      were measured against student performance in five areas: 1) tutorial session, 2)
      midterm examination, 3) final examination, 4) preclinical laboratory, and 5)
      overall cumulative course grade. Student performance in each of the five areas
      measured against combinations of tutor subject matter expertise and tutoring
      experience level showed no statistically significant difference between the
      groups in the overall course grade. However, student performance in the expert
      group showed a significant difference in the final examination compared to the
      nonexpert group (p<0.05). Also, students in the group consisting of expert tutors
      with no experience performed better on the final examination compared to those
      students who had expert tutors with experience (p<0.05). The results indicate
      that overall student performance in the problem-based Restorative Treatment
      course is not affected by tutor expertise or prior tutoring experience.

PMID- 17554100
TI  - Evidence-based dentistry: a model for clinical practice.
AB  - Making decisions in dentistry should be based on the best evidence available. The
      objective of this study was to demonstrate a practical procedure and model that
      clinicians can use to apply the results of well-conducted studies to patient care
      by critically appraising the evidence with checklists and letter grade scales. To
      demonstrate application of this model for critically appraising the quality of
      research evidence, a hypothetical case involving an adult male with chronic
      periodontitis is used as an example. To determine the best clinical approach for
      this patient, a four-step, evidence-based model is demonstrated, consisting of
      the following: definition of a research question using the PICO format, search
      and selection of relevant literature, critical appraisal of identified research
      reports using checklists, and the application of evidence. In this model, the
      quality of research evidence was assessed quantitatively based on different
      levels of quality that are assigned letter grades of A, B, and C by evaluating
      the studies against the QUOROM (Quality of Reporting Meta-Analyses) and CONSORT
      (Consolidated Standards of Reporting Trials) checklists in a tabular format. For
      this hypothetical periodontics case, application of the model identified the best
      available evidence for clinical decision making, i.e., one randomized controlled
      trial and one systematic review of randomized controlled trials. Both studies
      showed similar answers for the research question. The use of a letter grade scale
      allowed an objective analysis of the quality of evidence. A checklist-driven
      model that assesses and applies evidence to dental practice may substantially
      improve dentists' decision making skill.

PMID- 17554101
TI  - Occupational exposure to bloodborne pathogens and management of exposure
      incidents in Nigerian dental schools.
AB  - The goal of this study was to determine the frequency of occupational exposures
      to bloodborne pathogens amongst Nigerian clinical dental students, their HBV
      vaccination status, and reporting practices. A cross-sectional study of all
      clinical dental students in the four Nigerian dental schools was carried out by
      means of an anonymous self-administered questionnaire that asked questions on
      demography, number and type of exposure, management of the exposures, personal
      protection against cross infection, and the reporting of such exposures. One
      hundred and fifty-three students responded (response rate of 84.5 percent). Only
      thirty-three (37.9 percent) were fully vaccinated against HBV. Ninety (58.8
      percent) of the students have had at least one occupational exposure. There was
      no significantly associated difference between sex, age, location of school, and
      exposure. Most of the exposures (44.4 percent) occurred in association with
      manual tooth cleaning. There was inadequate protection of the eyes. None of the
      exposures were formally reported. It is the responsibility of training
      institutions to ensure the safety of the students by mandatory HBV vaccination
      prior to exposure and adequate training in work safety. Written policies and
      procedures should be developed and made easily accessible to all workers to
      facilitate prompt reporting and management of all occupational exposures.

PMID- 17554102
TI  - Anterior clavicle dislocation associated with acromioclavicular dislocation in a
      soccer player: a case report.

PMID- 17554103
TI  - Comparison of tibial graft fixation between simulated arthroscopic and open inlay
      techniques for posterior cruciate ligament reconstruction.
AB  - BACKGROUND: Techniques for reconstruction of the posterior cruciate ligament
      continue to evolve to improve clinical results. Recent arthroscopic
      reconstruction methods using tibial inlay grafts require suture fixation to avoid
      a posterior approach to the knee. HYPOTHESIS: Early strength of the tibial
      fixation of posterior cruciate ligament inlay grafts, designed for an
      arthroscopic approach and using suture fixation, is not significantly different
      than that of open technique grafts using screw fixation. STUDY DESIGN: Controlled
      laboratory study. METHODS: Six paired human tibias were randomized to a
      reconstruction using an open inlay technique with two 4.0-mm cancellous lag
      screws or an instrumented technique suitable for an all-arthroscopic approach
      using 2 No. 5 Ethibond sutures tied over a button on the anterior tibial cortex.
      Cyclic testing of each construct was done before loading to failure. RESULTS: The
      loads for each group at 3-mm displacement and at 5-mm displacement were not found
      to be significantly different. Ultimate load for the screw group was 762 N and
      for the suture group was 582 N (P =.31). Stiffness was 89.8 N/mm for the screw
      inlays and 85.1 N/mm for the suture inlays (P =.68). Cyclic testing demonstrated
      no advantages of screw fixation over sutures. No suture failure was noted.
      CONCLUSION: The suture fixation technique for tibial inlay posterior cruciate
      ligament reconstruction appears to approximate the early strength of screw
      fixation. CLINICAL RELEVANCE: Arthroscopic techniques for tibial inlay
      reconstruction of the posterior cruciate ligament requiring suture fixation may
      offer similar initial biomechanical fixation as current open inlay techniques
      without the need for an open posterior knee approach.

PMID- 17554104
TI  - Equivalent clinical results of arthroscopic single-row and double-row suture
      anchor repair for rotator cuff tears: a randomized controlled trial.
AB  - BACKGROUND: Restoring the anatomical footprint may improve the healing and
      mechanical strength of repaired tendons. A double row of suture anchors increases
      the tendon-bone contact area, reconstituting a more anatomical configuration of
      the rotator cuff footprint. HYPOTHESIS: There is no difference in clinical and
      imaging outcome between single-row and double-row suture anchor technique repairs
      of rotator cuff tears. STUDY DESIGN: Randomized controlled trial; Level of
      evidence, 1. METHODS: The authors recruited 60 patients. In 30 patients, rotator
      cuff repair was performed with a single-row suture anchor technique (group 1). In
      the other 30 patients, rotator cuff repair was performed with a double-row suture
      anchor technique (group 2). RESULTS: Eight patients (4 in the single-row anchor
      repair group and 4 in the double-row anchor repair group) did not return at the
      final follow-up. At the 2-year follow-up, no statistically significant
      differences were seen with respect to the University of California, Los Angeles
      score and range of motion values. At 2-year follow-up, postoperative magnetic
      resonance arthrography in group 1 showed intact tendons in 14 patients, partial
      thickness defects in 10 patients, and full-thickness defects in 2 patients. In
      group 2, magnetic resonance arthrography showed an intact rotator cuff in 18
      patients, partial-thickness defects in 7 patients, and full-thickness defects in
      1 patient. CONCLUSION: Single- and double-row techniques provide comparable
      clinical outcome at 2 years. A double-row technique produces a mechanically
      superior construct compared with the single-row method in restoring the
      anatomical footprint of the rotator cuff, but these mechanical advantages do not
      translate into superior clinical performance.

PMID- 17554105
TI  - Preserved fertility in a non-mosaic Klinefelter patient with a mutation in the
      fibroblast growth factor receptor 3 gene: case report.
AB  - Patients with Klinefelter syndrome (47,XXY) are characterized by eunuchoid body
      proportions, gynaecomastia, small firm testes and azoospermia. We describe a
      Klinefelter patient (non-mosaic 47,XXY karyotype) who was heterozygous for the
      classical 1138G>A mutation in the fibroblast growth factor receptor 3 (FGFR3)
      gene, which is a gain-of-function mutation resulting in achondroplasia. The
      patient had phenotypic characteristics of achondroplasia (e.g. short limbed
      dwarfism and frontal bossing). Testicular volume was 8 ml at 27 years of age and
      repeated semen samples showed sperm concentrations of 0.175 million/ml. Serum FSH
      levels were elevated (21.7 IU/l) compared to normal age-matched healthy male
      controls and patients with non-mosaic Klinefelter syndrome, and inhibin B levels
      were low-normal, in contrast to the usually undetectable inhibin B levels in
      adult Klinefelter patients. The patient fathered a child from a spontaneous
      pregnancy. The observed testicular size and function in our patient contrast the
      typical findings in classical Klinefelter syndrome. We speculate that the
      alteration of FGFR3 protein function in our Klinefelter patient alleviated the
      destruction of the seminiferous tubules and may suggest that the fibroblast
      growth factor family has a pleiotrophic function in human spermatogonia, which
      physiologically express FGFR3.

PMID- 17554106
TI  - Evaluation of the potential for pharmacodynamic and pharmacokinetic drug
      interactions between selegiline transdermal system and two sympathomimetic agents
      (pseudoephedrine and phenylpropanolamine) in healthy volunteers.
AB  - Selegiline transdermal system is a recently approved monoamine oxidase inhibitor
      antidepressant. Medications that inhibit monoamine oxidase type A can augment the
      pressor effects of sympathomimetic amines, increasing the potential for
      hypertensive crisis. This study examined the potential for drug-drug interactions
      during treatment with selegiline transdermal system and pseudoephedrine or
      phenylpropanolamine. Two studies were conducted with 25 healthy volunteers to
      assess changes in blood pressure and heart rate during administration of
      pseudoephedrine or phenylpropanolamine alone or together with selegiline
      transdermal system. No significant differences in mean maximum changes in vital
      signs occurred with pseudoephedrine. No significant differences were found in
      mean maximum changes in systolic heart rate with phenylpropanolamine; however, 4
      of 12 subjects each experienced 1 isolated protocol-defined minimal pressor
      response without concurrent adverse effects (1 with phenylpropanolamine alone; 3
      with phenylpropanolamine + selegiline transdermal system). Pharmacokinetic
      parameters obtained following selegiline transdermal system and pseudoephedrine
      or phenylpropanolamine were unremarkable. The results suggest that selegiline
      transdermal system 6 mg/24 h does not significantly alter the pharmacodynamics or
      pharmacokinetics of either pseudoephedrine or phenylpropanolamine when
      administered to healthy volunteers; however, it is prudent to avoid
      coadministration of selegiline transdermal system and sympathomimetics.

PMID- 17554107
TI  - Under-reporting of deaths to the coroner by doctors: a retrospective review of
      deaths in two hospitals in Melbourne, Australia.
AB  - BACKGROUND: 'Under-reporting' of deaths to the coroner has significant
      implications for the identification and investigation of preventable deaths. In
      extreme cases, it may even be a symptom of the system failures that allowed cases
      such as Harold Shipman, Australia's King Edward Memorial Hospital, the alleged
      incidents at the Bundaberg Hospital and the Bristol Royal Infirmary to persist.
      Several initiatives in Australia and the UK are currently reviewing the coroner's
      system in light of the recommendations made by the Luce report and the Bundaberg
      Hospital inquiry to consider whether the coroner's system effectively meets the
      needs of our society, including the healthcare sector. Reporting of deaths to the
      coroner is a key issue for consideration in this debate. OBJECTIVE: This study's
      primary aim is to identify the number of deaths in the hospital setting that meet
      the reporting criteria set out by the coroner's Act, Victoria 1985 ('reportable
      deaths'). METHOD: This study utilized a method of retrospective structured
      medical record review of in-patients who died between 1 January 2002 and 30 June
      2003 at two major public hospitals in Victoria, Australia. RESULTS: In total, 229
      cases (95.4% of records requested) were included in this review (120 from
      Hospital A and 109 from Hospital B). The number of cases at both hospitals
      meeting the coroner's reporting criterion was 58, of which, 22 (37.9%) were
      reported to the coroner. CONCLUSION: This study provides the first experimental
      evidence of significant 'under-reporting' of deaths to the coroner by hospitals.
      This is an important consideration for the reform initiatives currently underway.
      Better communication channels need to be fostered between doctors and coroners if
      coronial investigations are to be used effectively for reviewing deaths in
      hospitals.

PMID- 17554108
TI  - Copious pre-ejaculation: small glands-major headaches.

PMID- 17554109
TI  - Mice lacking Raf kinase inhibitor protein-1 (RKIP-1) have altered sperm
      capacitation and reduced reproduction rates with a normal response to testicular
      injury.
AB  - Raf kinase inhibitor protein-1 (RKIP-1) belongs to the phosphatidyl ethanolamine
      binding family of proteins (PEBP), which are highly conserved throughout
      evolution and widely expressed in tissues of mammalian organisms. RKIP-1 is a
      modulator of extracellular signal-regulated kinase (ERK), nuclear factor-kappa B
      (NF-kappaB), and G protein coupled receptor (GPCR) signaling cascades and is
      implicated as a factor in numerous physiological processes and disease states
      including metastasis. Testicular germ cells also express high levels of RKIP mRNA
      during spermatogenesis, particularly from late pachytene spermatocytes through
      step 15 elongate spermatids. Therefore, the sensitivity of spermatogenesis to
      injury was compared in wild-type and RKIP-1(-/-) mice. Unlike what has been
      described with tumor suppressors such as p53, RKIP-1(-/-) and wild-type mice were
      equally sensitive to germ cell toxicity by x-irradiation as assessed by terminal
      deoxynucleotidyl transferase biotin-deoxyuridine triphosphate (dUTP) nick end
      labeling (TUNEL) positivity 9 hours after a 5 Gy exposure and testicular
      spermatid head counts 15.5 days after 0.5 Gy exposure. Recent findings also
      indicate that RKIP is a decapacitation factor receptor on sperm. The present
      study demonstrates that sperm from RKIP-deficient mice are precociously
      capacitated compared with their wild-type counterparts. Data from mating
      experiments indicate decreased reproduction rates between crosses of RKIP-1(-/-)
      male mice and either heterozygous or RKIP-1(-/-) females. Furthermore, RKIP
      immunolocalization of epididymal sperm supports transfer of the protein from germ
      cell cytoplasm to the sperm via the cytoplasmic droplet during epididymal
      transport. Overall, these studies indicate an important role for RKIP in
      reproduction as a modulator of capacitation but not in the regulation of
      testicular injury.

PMID- 17554110
TI  - Comparative analysis of interindividual variations in the seminal plasma proteome
      of fertile men with identification of potential markers for azoospermia in
      infertile patients.
AB  - Seminal plasma is a potential source of biomarkers for many disorders of the male
      reproductive system. The identification and characterization of proteins in the
      seminal plasma by using two-dimensional (2-D) difference gel electrophoresis
      (DIGE) serve as a basis for estimating male infertility. However, individual
      variation remains an impediment to identifying disease-associated proteins.
      Therefore, it is necessary to examine the interindividual variations in the
      seminal plasma proteome of fertile men. The present study analyzed seminal plasma
      samples from 10 fertile men. The results from silver-stained 2-D DIGE were
      averaged to reduce gel to gel variations. Up to 501 spots (polypeptides) were
      detected on the averaged gels for the fertile men. The coefficient of variation
      (CV) of standardized abundance was calculated for 63 spots that were common to
      all 10 samples; the CV values ranged from 24.5% to 129.9% with a median value of
      63.1%. These results demonstrate that the variability in protein expression among
      different fertile men is relatively high in seminal plasma compared with that in
      other human tissue samples. The 63 matched spots were compared with those from 10
      patients with azoospermia. There was no common spot that was lost in all of the
      10 patients, and 16 of these spots (25%) were present in each of the patients. We
      identified 4 and 1 candidate markers for nonobstructive and obstructive
      azoospermia, respectively. These results validate our method of identifying
      differences in the proteomic profiles of seminal plasma samples and provide an
      important basis for protein expression profiling and comparative proteomics of
      infertility.

PMID- 17554111
TI  - Effects of ejaculation-to-analysis delay on levels of markers of epididymal and
      accessory sex gland functions and sperm motility.
AB  - This study aimed to examine the association between the interval from ejaculation
      to analysis and epididymal and accessory sex gland function in relation to sperm
      motility. Ejaculates from 1079 men assessed for infertility were analyzed
      according to World Health Organization guidelines. Biochemical markers were
      measured in semen to assess the function of the epididymis (neutral alpha
      glucosidase [NAG]), prostate (prostate-specific antigen [PSA] and zinc), and
      seminal vesicles (fructose). Three groups were defined according to time from
      ejaculation to analysis: G(< or =30) (24-30 minutes), G(31-60) (31-60 minutes),
      and G(>60) (63-180 minutes). The proportion of progressively motile sperm was
      significantly lower in G(>60) than in G(< or =30) (mean difference, 8.0%; 95%
      confidence interval [CI], 2.0%-13%) or G(31-60) (mean difference, 6.0%; 95% CI,
      1.0%-12%). The proportion of rapid progressive sperm motility was significantly
      higher in G(< or =30) compared with G(31-60) (mean difference, 3.0%; 95% CI, 1.0%
      5.0%) and G(>60) (mean difference, 6.0%; 95% CI, 1.0%-10%). Sperm morphology and
      viability did not vary significantly between the groups. However, PSA levels in
      G(>60) were 29% and 31% significantly lower than in G(< or =30) (95% CI, 3.0%
      54%) and G(31-60) (95% CI, 7.0%-58%), respectively. Moreover, men in G(>60) had
      29% and 17% significantly lower zinc compared with those in G(< or =30) (95% CI,
      4.0%-69%) and G(31-60) (95% CI, 4.0%-64%), respectively. Levels of NAG and
      fructose did not differ significantly between the groups. There were negative
      associations between the ejaculation-to-analysis interval and sperm motility and
      levels of PSA and zinc. In male infertility assessments, semen analysis should be
      performed within 60 minutes of ejaculation.

PMID- 17554112
TI  - Walking in a city neighbourhood, paving the way.
AB  - BACKGROUND: There is an increasing interest in the use of walking routes to
      promote physical activity. We explored the stated attitudes of selected residents
      from two adjacent low-income city neighbourhoods towards walking. This was in
      response to negative results obtained in a quantitative study assessing the
      impact of the Sli-na-Slainte (path to health), a signed heart health walking
      route. METHOD: This was a qualitative focus group study. RESULTS: The impact of
      the walking route was marginal. Four major themes influencing local walking
      emerged, centring on the social and physical environment. CONCLUSION: Findings
      suggest that the neighbourhoods are unreceptive to health promotion initiatives
      such as the Sli-na-Slainte since residents are dealing with fundamental social
      and physical environmental issues. Initiatives such as the Sli-na-Slainte need to
      be embedded in a supportive and facilitative environment if they are to achieve
      substantial impact.

PMID- 17554113
TI  - Image in clinical medicine. Chronic calcific pancreatitis.

PMID- 17554114
TI  - The stem-cell market - patents and the pursuit of scientific progress.

PMID- 17554115
TI  - Discovery of new infectious diseases - bartonella species.

PMID- 17554116
TI  - Eprodisate for the treatment of renal disease in AA amyloidosis.
AB  - BACKGROUND: Amyloid A (AA) amyloidosis is a complication of chronic inflammatory
      conditions that develops when proteolytic fragments of serum amyloid A protein
      (SAA) are deposited in tissues as amyloid fibrils. Amyloid deposition in the
      kidney causes progressive deterioration in renal function. Eprodisate is a member
      of a new class of compounds designed to interfere with interactions between
      amyloidogenic proteins and glycosaminoglycans and thereby inhibit polymerization
      of amyloid fibrils and deposition of the fibrils in tissues. METHODS: We
      performed a multicenter, randomized, double-blind, placebo-controlled trial to
      evaluate the efficacy and safety of eprodisate in patients with AA amyloidosis
      and kidney involvement. We randomly assigned 183 patients from 27 centers to
      receive eprodisate or placebo for 24 months. The primary composite end point was
      an assessment of renal function or death. Disease was classified as worsened if
      any one of the following occurred: doubling of the serum creatinine level,
      reduction in creatinine clearance by 50% or more, progression to end-stage renal
      disease, or death. RESULTS: At 24 months, disease was worsened in 24 of 89
      patients who received eprodisate (27%) and 38 of 94 patients given placebo (40%,
      P=0.06); the hazard ratio for worsening disease with eprodisate treatment was
      0.58 (95% confidence interval, 0.37 to 0.93; P=0.02). The mean rates of decline
      in creatinine clearance were 10.9 and 15.6 ml per minute per 1.73 m(2) of body
      surface area per year in the eprodisate and the placebo groups, respectively
      (P=0.02). The drug had no significant effect on progression to end-stage renal
      disease (hazard ratio, 0.54; P=0.20) or risk of death (hazard ratio, 0.95;
      P=0.94). The incidence of adverse events was similar in the two groups.
      CONCLUSIONS: Eprodisate slows the decline of renal function in AA amyloidosis.
      (ClinicalTrials.gov number, NCT00035334.)

PMID- 17554117
TI  - Natural history and outcome in systemic AA amyloidosis.
AB  - BACKGROUND: Deposition of amyloid fibrils derived from circulating acute-phase
      reactant serum amyloid A protein (SAA) causes systemic AA amyloidosis, a serious
      complication of many chronic inflammatory disorders. Little is known about the
      natural history of AA amyloidosis or its response to treatment. METHODS: We
      evaluated clinical features, organ function, and survival among 374 patients with
      AA amyloidosis who were followed for a median of 86 months. The SAA concentration
      was measured serially, and the amyloid burden was estimated with the use of whole
      body serum amyloid P component scintigraphy. Therapy for inflammatory diseases
      was administered to suppress the production of SAA. RESULTS: Median survival
      after diagnosis was 133 months; renal dysfunction was the predominant disease
      manifestation. Mortality, amyloid burden, and renal prognosis all significantly
      correlated with the SAA concentration during follow-up. The risk of death was
      17.7 times as high among patients with SAA concentrations in the highest eighth,
      or octile, (>or=155 mg per liter) as among those with concentrations in the
      lowest octile (<4 mg per liter); and the risk of death was four times as high in
      the next-to-lowest octile (4 to 9 mg per liter). The median SAA concentration
      during follow-up was 6 mg per liter in patients in whom renal function improved
      and 28 mg per liter in those in whom it deteriorated (P<0.001). Amyloid deposits
      regressed in 60% of patients who had a median SAA concentration of less than 10
      mg per liter, and survival among these patients was superior to survival among
      those in whom amyloid deposits did not regress (P=0.04). CONCLUSIONS: The effects
      of renal dysfunction dominate the course of AA amyloidosis, which is associated
      with a relatively favorable outcome in patients with SAA concentrations that
      remain in the low-normal range (<4 mg per liter).

PMID- 17554118
TI  - Adjuvant mitotane treatment for adrenocortical carcinoma.
AB  - BACKGROUND: Adrenocortical carcinoma is a rare neoplasm characterized by a high
      risk of recurrence after radical resection. Whether the use of mitotane is
      beneficial as an adjuvant treatment has been controversial. Our aim was to
      evaluate the efficacy of adjuvant mitotane in prolonging recurrence-free
      survival. METHODS: We performed a retrospective analysis involving 177 patients
      with adrenocortical cancer who had undergone radical surgery at 8 centers in
      Italy and 47 centers in Germany between 1985 and 2005. Adjuvant mitotane was
      administered to 47 Italian patients after radical surgery (mitotane group),
      whereas 55 Italian patients and 75 German patients (control groups 1 and 2,
      respectively) did not receive adjuvant treatment after surgery. RESULTS: Baseline
      features in the mitotane group and the control group from Italy were similar; the
      German patients were significantly older (P=0.03) and had more stage I or II
      adrenocortical carcinomas (P=0.02) than did patients in the mitotane group.
      Recurrence-free survival was significantly prolonged in the mitotane group, as
      compared with the two control groups (median recurrence-free survival, 42 months,
      as compared with 10 months in control group 1 and 25 months in control group 2).
      Hazard ratios for recurrence were 2.91 (95% confidence interval [CI], 1.77 to
      4.78; P<0.001) and 1.97 (95% CI, 1.21 to 3.20; P=0.005), respectively.
      Multivariate analysis indicated that mitotane treatment had a significant
      advantage for recurrence-free survival. Adverse events associated with mitotane
      were mainly of grade 1 or 2, but temporary dose reduction was needed in 13% of
      patients. CONCLUSIONS: Adjuvant mitotane may prolong recurrence-free survival in
      patients with radically resected adrenocortical carcinoma.

PMID- 17554119
TI  - Bacteremia, fever, and splenomegaly caused by a newly recognized bartonella
      species.
AB  - Bartonella species cause serious human infections globally, including bacillary
      angiomatosis, Oroya fever, trench fever, and endocarditis. We describe a patient
      who had fever and splenomegaly after traveling to Peru and also had bacteremia
      from an organism that resembled Bartonella bacilliformis, the causative agent of
      Oroya fever, which is endemic to Peru. However, genetic analyses revealed that
      this fastidious bacterium represented a previously uncultured and unnamed
      bartonella species, closely related to B. clarridgeiae and more distantly related
      to B. bacilliformis. We characterized this isolate, including its ability to
      cause fever and sustained bacteremia in a rhesus macaque. The route of infection
      and burden of human disease associated with this newly described pathogen are
      currently unknown.

PMID- 17554120
TI  - Explaining the decrease in U.S. deaths from coronary disease, 1980-2000.
AB  - BACKGROUND: Mortality from coronary heart disease in the United States has
      decreased substantially in recent decades. We conducted a study to determine how
      much of this decrease could be explained by the use of medical and surgical
      treatments as opposed to changes in cardiovascular risk factors. METHODS: We
      applied a previously validated statistical model, IMPACT, to data on the use and
      effectiveness of specific cardiac treatments and on changes in risk factors
      between 1980 and 2000 among U.S. adults 25 to 84 years old. The difference
      between the observed and expected number of deaths from coronary heart disease in
      2000 was distributed among the treatments and risk factors included in the
      analyses. RESULTS: From 1980 through 2000, the age-adjusted death rate for
      coronary heart disease fell from 542.9 to 266.8 deaths per 100,000 population
      among men and from 263.3 to 134.4 deaths per 100,000 population among women,
      resulting in 341,745 fewer deaths from coronary heart disease in 2000.
      Approximately 47% of this decrease was attributed to treatments, including
      secondary preventive therapies after myocardial infarction or revascularization
      (11%), initial treatments for acute myocardial infarction or unstable angina
      (10%), treatments for heart failure (9%), revascularization for chronic angina
      (5%), and other therapies (12%). Approximately 44% was attributed to changes in
      risk factors, including reductions in total cholesterol (24%), systolic blood
      pressure (20%), smoking prevalence (12%), and physical inactivity (5%), although
      these reductions were partially offset by increases in the body-mass index and
      the prevalence of diabetes, which accounted for an increased number of deaths (8%
      and 10%, respectively). CONCLUSIONS: Approximately half the decline in U.S.
      deaths from coronary heart disease from 1980 through 2000 may be attributable to
      reductions in major risk factors and approximately half to evidence-based medical
      therapies.

PMID- 17554121
TI  - Local therapy and survival in breast cancer.

PMID- 17554122
TI  - Image in clinical medicine. Amyloid purpura.

PMID- 17554123
TI  - Clinical problem solving. A hand-carried diagnosis.

PMID- 17554124
TI  - Advances in the treatment of amyloidosis.

PMID- 17554125
TI  - Adjuvant mitotane therapy of adrenal cancer - use and controversy.

PMID- 17554126
TI  - Why does rheumatoid arthritis involve the joints?

PMID- 17554127
TI  - Hepatitis E vaccine.

PMID- 17554128
TI  - Improving the management of chronic disease.

PMID- 17554129
TI  - Amiodarone for atrial fibrillation.

PMID- 17554130
TI  - Solicitation of deceased and living organ donors.

PMID- 17554131
TI  - Into the woods.

PMID- 17554132
TI  - Intraaortic vegetations and infective endocarditis.

PMID- 17554133
TI  - Acute Wiiitis.

PMID- 17554134
TI  - TLRs in the Gut. IV. Negative regulation of Toll-like receptors and intestinal
      homeostasis: addition by subtraction.
AB  - Toll-like receptors (TLRs) are a family of transmembrane proteins that recognize
      conserved molecular motifs on microorganisms. Ligand binding to TLRs initiates
      signaling cascades that activate NF-kappaB, MAPK, and interferon response
      factors. These culminate in cellular responses including activation of
      antimicrobial killing mechanisms, production of cytokines and chemokines,
      maturation of antigen presenting cells, and the recruitment of the adaptive
      immune response. Intestinal epithelial cells represent a unique population of
      cells that exist in direct contact with a biomass of bacteria. Initiation of TLR
      signaling is tightly regulated because prolonged and excessive activation of TLRs
      can lead to uncontrolled inflammation detrimental to the host. Varied mechanisms
      appear to contribute to control of TLR activation in the intestinal epithelium.
      These include the collective effects of several negative regulators that include
      IRAK-M, TOLLIP, SIGIRR, A20, Nod2, and PPARgamma. However, it remains to be
      determined whether they comprise the entire spectrum of negative control
      mechanisms and how they are bypassed to trigger activation during challenge by
      pathogens.

PMID- 17554135
TI  - Omission of citing prior work.

PMID- 17554138
TI  - Parental preferences on addressing weight-related issues in children.
AB  - Little is known about parental preferences on how providers should approach or
      manage weight-related concerns. A cross-sectional survey was conducted of 292
      parents in a pediatric primary care faculty group practice. Of the 292
      respondents, 90% were women, 45% had a child on Medicaid, and 53% had a body mass
      index of 25 or more. Only 12.1% of parents reported they had an overweight child.
      The term "gaining too much weight" was preferred 2:1 to "overweight" (51.1%
      versus 25.9%, P < .001). Most respondents (62.3%) thought the physician's office
      was the best place to manage an overweight child. Parents who reported they had
      an overweight child were more likely to prefer individual than group sessions
      compared with those without an overweight child (odds ratio, 2.1; 95% confidence
      interval, 1.2-3.7). Further research is needed to investigate the reasons
      underlying these preferences and how they positively or negatively impact program
      satisfaction, attrition rates, and behavior change outcomes.

PMID- 17554139
TI  - Intrapelvic migration with long-term retention of a rectal thermometer: a case
      report.
AB  - Rectal perforation is a serious complication of manipulation of the anus and
      rectum, with catheters and thermometers. Such procedures should be performed with
      caution. We report a case of a 19-year-old male with retention of an intrapelvic
      foreign body, a mercury thermometer, which after perforating the rectum migrated
      into the pelvis and remained there without any symptoms for the next 7 years. A
      mercury thermometer, broken into 2 fragments, retained in the pelvis was noted
      accidentally by pelvic roentgenogram examination. An extrinsic thermometer tip
      over the upper rectal region was palpable by digital rectal examination. On
      physical examination, no infections or signs of peritonitis were observed. There
      were no significant abnormal findings by flexible colonoscopy. Computed
      tomography revealed a foreign body retained in the pelvis. Blood mercury level
      and a 24-hour urinary measurement of mercury were within normal limits. The
      patient refused any further treatment since he did not have any discomfort. The
      patient was in good condition and had not had surgery in the preceding 7 years.

PMID- 17554140
TI  - A prospective study of rotavirus diarrhea in children under 1 year of age.
AB  - The aim of this study was to document the changing clinical profile and prognosis
      of acute diarrhea in infants. This was a prospective observational study with
      follow-up. Demographic, anthropometric, and clinical data were collected in
      children younger than 1 year with acute diarrhea. Stool was examined under the
      microscope, cultured, tested for presence of reducing substance and occult blood,
      and subjected to electrophoresis to detect rotavirus infection. Thirty-one
      (91.2%) of the 34 infants were breastfed, 18 exclusively and 13 partially. Twenty
      three had rotavirus infection and had slower nutritional recovery than others.
      There was no difference in the incidence of rotavirus infection between
      exclusively and partially breastfed infants. Continuation of feeds containing
      lactose did not affect prognosis, though 23 (67.6%) infants had reducing
      substance in stool. We documented a high incidence of rotavirus infection, which
      negatively affected growth of infants by some ill-defined mechanism. Failure of
      exclusive breastfeeding to protect against rotavirus infection highlights the
      need for universal rotavirus vaccination. Lactose malabsorption detected in many
      infants did not affect prognosis after acute diarrhea.

PMID- 17554141
TI  - Angioedema.

PMID- 17554142
TI  - Epstein-Barr Virus Associated Nasopharyngeal Carcinoma and Local Polymorphic B
      Cell Lymphoproliferative Disorder in a Patient With HIV Disease.
AB  - A rare case report of HIV-associated nasopharyngeal carcinoma concurrent with
      local polymorphic B-cell lymphoproliferative disorder is reported and discussed
      on the ground of the most recent literature evidences. Only very few reports of
      nasopharyngeal carcinoma have been described until now in patients infected with
      HIV (one case in adults), and a coexisting lymphoid cell proliferation with a
      concurrent role of Epstein-Barr virus in prompting both disorders was never
      reported to date. The relevant pathogenetic, diagnostic, and therapeutic
      questions raised by this infrequent intriguing association retrieved in a patient
      with prominent HIV-related immunodeficiency are focused on.

PMID- 17554143
TI  - Cross-sectional population-based study of knowledge, attitudes, and practices
      regarding HIV/AIDS in Dakshina Kannada district of Karnataka, India.
AB  - OBJECTIVE: To assess HIV/AIDS-related knowledge, attitudes, and practices among
      the general population in South India. METHODS: The 1669 participants (834 males,
      835 females) aged 19-49 years were surveyed using a stratified 2-stage random
      sampling design with probability proportional to size. RESULTS: Although 54% of
      participants knew that AIDS is caused by "HIV" virus and 44% could correctly
      identify all modes of transmission, 52% believed in one or more myths, 41% did
      not know that condoms can prevent HIV, and 18% had not heard of a condom. Higher
      HIV knowledge scores were significantly associated with male gender, higher
      education, currently married, higher frequency of reading newspapers, listening
      to radio or watching television, and willingness to get tested for HIV (P < .01).
      Thirty-four percent felt that HIV-infected individuals should be kept away from
      others, and 40% were not willing to accept a family member with HIV. There was a
      significant and positive correlation between knowledge and attitude scores (P <
      .01). Among respondents who ever had sexual intercourse, significantly more males
      declared having more than one sexual partner compared to females (P < .01). Only
      16% of respondents reported that they consistently used condoms. Sixty-two
      percent of the respondents were willing to undergo an HIV test if provided free
      of cost. This willingness to opt for HIV testing increased significantly with
      better knowledge score, better attitude score, and higher education status (P <
      .01). CONCLUSIONS: HIV/AIDS prevention campaigns in India should focus on public
      education, stigma reduction, promotion of condom use, and risk-reduction
      behaviors in urban and rural communities targeted toward young adults.

PMID- 17554144
TI  - Novel synthetic ceramide derivatives increase intracellular calcium levels and
      promote epidermal keratinocyte differentiation.
AB  - Ceramide is an important constituent of stratum corneum lipids, which act as both
      physical barriers and signal modulators. We synthesized several ceramide
      derivatives and investigated their effects on keratinocyte differentiation. RT
      PCR and Western blotting showed that the novel synthetic ceramide derivatives
      K6PC-4 [N-(2,3-dihydroxypropyl)-2-hexyl-3-oxo-decanamide], K6PC-5, [N-(1,3
      dihydroxypropyl-2-hexyl-3-oxo-decanamide] and K6PC-9 (N-ethanol-2-hexyl-3-oxo
      decanamide) [corrected] These ceramide derivatives elicited a rapid transient
      increase in intracellular calcium levels, which were measured using laser
      scanning confocal microscopy. In addition, K6PC-4, K6PC-5, and K6PC-9 stimulated
      the phosphorylation of p42/44 extracellular signal-regulated kinase and c-Jun N
      terminal kinase. In a reconstituted epidermis model, K6PC-4, K6PC-5, and K6PC-9
      significantly increased keratin 1 expression in the suprabasal layer. These
      results indicate that these novel synthetic ceramide derivatives have the
      potential to promote keratinocyte differentiation, suggesting that the lipid
      molecules are applicable for treating skin diseases involving abnormal
      keratinocyte differentiation.

PMID- 17554145
TI  - Association of atheroma as assessed by intraoperative transoesophageal
      echocardiography with long-term mortality in patients undergoing cardiac surgery.
AB  - AIMS: To determine whether the presence and severity of aortic atheroma predict
      long-term all-cause mortality among patients undergoing cardiac surgery. METHODS
      AND RESULTS: We followed 8,581 patients who underwent cardiac surgery and had
      routine intraoperative transoesophageal echocardiography for 2.8 years (range
      0.06-6.0 years). Data regarding multiple potential confounders were prospectively
      collected and electronically recorded. There were 2,878 (34%) patients with no
      atheroma; 4,129 (48%) patients with mild atheroma; 1,215 (14%) with moderate
      atheroma; and 359 (4%) with severe atheroma. There were 1000 deaths. Death rates
      were increased in patients with moderate [relative risk (RR) 3.29, 95% CI 2.50
      4.32, P < 0.0001) and severe atheroma (RR 5.21, 95% CI 3.65-7.41, P < 0.0001).
      After adjusting for multiple other confounders, severe atheroma remained modestly
      predictive of risk (adjusted RR 1.46, 95% CI 1.07-2.00, P = 0.02); but moderate
      atheroma and mild atheroma were not predictive of increased risk. In a propensity
      analysis that matched patients with comparable range of variables, severe
      atheroma was no longer predictive of risk (adjusted RR 1.39, 95% CI 0.87-2.23, P
      = 0.17). CONCLUSION: Our study shows that severe atheroma is associated with
      increased long-term mortality in patients undergoing cardiac surgery; however,
      the relationship is weak using propensity analysis, suggesting no causal
      association.

PMID- 17554146
TI  - Role of hyperphosphatemia and 1,25-dihydroxyvitamin D in vascular calcification
      and mortality in fibroblastic growth factor 23 null mice.
AB  - Fibroblastic growth factor 23 (FGF23) regulates renal phosphate reabsorption and
      1alpha-hydroxylase activity. Ablation of FGF23 results in elevated serum
      phosphate, calcium, and 1,25-dihydroxyvitamin D3 [1,25(OH)(2)D] levels; vascular
      calcifications; and early death. For determination of the independent roles of
      hyperphosphatemia and excess vitamin D activity on the observed phenotypic
      abnormalities, FGF23 null mice were fed a phosphate- or vitamin D-deficient diet.
      The phosphate-deficient diet corrected the hyperphosphatemia, prevented vascular
      calcifications, and rescued the lethal phenotype in FGF23 null mice, despite
      persistent elevations of serum 1,25(OH)(2)D and calcium levels. This suggests
      that hyperphosphatemia, rather than excessive vitamin D activity, is the major
      stimulus for vascular calcifications and contributes to the increased mortality
      in the FGF23-null mouse model. In contrast, the vitamin D-deficient diet failed
      to correct either the hyperphosphatemia or the vascular calcifications in FGF23
      null mice, indicating that FGF23 independently regulates renal phosphate
      excretion and that elevations in 1,25(OH)(2)D and calcium are not sufficient to
      induce vascular calcifications in the absence of hyperphosphatemia. The vitamin D
      deficient diet also improved survival in FGF23 null mice in association with
      normalization of 1,25(OH)(2)D and calcium levels and despite persistent
      hyperphosphatemia and vascular calcifications, indicating that excessive vitamin
      D activity can also have adverse effects in the presence of hyperphosphatemia and
      absence of FGF23. Understanding the independent and context-dependent
      interactions between hyperphosphatemia and excessive vitamin D activity, as well
      as vascular calcifications and mortality in FGF23 null mice, may ultimately
      provide important insights into the management of clinical disorders of
      hyperphosphatemia and excess vitamin D activity.

PMID- 17554147
TI  - Growth hormone treatment during hemodialysis in a randomized trial improves
      nutrition, quality of life, and cardiovascular risk.
AB  - Nutritional markers, such as lean body mass (LBM) and serum albumin, predict
      outcome in dialysis patients, in whom protein-energy malnutrition is associated
      with increased morbidity and mortality. The metabolic effects of human growth
      hormone (hGH) may improve the nutritional and cardiovascular health of these
      patients and consequently reduce morbidity and mortality. The aim of this study
      was to establish clinical proof of concept of hGH treatment for the improvement
      of the nutritional status in adult patients who are on maintenance hemodialysis.
      A total of 139 adult patients who were on maintenance hemodialysis and had serum
      albumin levels < or =40 g/L were randomly assigned to 6 mo of treatment with
      placebo or 20, 35, or 50 microg/kg per d hGH. Change in LBM and serum albumin
      (primary outcomes), health-related quality of life, and secondary efficacy and
      safety parameters were monitored. The study showed that hGH treatment increased
      LBM significantly at all dosage levels (2.5 kg [95% confidence interval 1.8 to
      3.1] versus -0.4 kg [95% confidence interval -1.4 to 0.6]; P < 0.001 for pooled
      hGH groups versus placebo). Serum albumin tended to increase (P = 0.076), serum
      transferrin (P = 0.001) and serum HDL (P < 0.038) increased, and plasma
      homocysteine was reduced (P = 0.029). TNF-alpha also tended to decrease with
      treatment (P = 0.134). An improvement in the Role Physical SF-36 quality-of-life
      subscale was observed (P = 0.042). There were no differences in clinically
      relevant adverse events between groups. In conclusion, hGH therapy safely
      improves LBM, other markers of mortality and morbidity, and health-related
      quality of life in adult patients who are on maintenance hemodialysis. A long
      term study is warranted to investigate whether these treatment benefits result in
      reduced mortality and morbidity.

PMID- 17554148
TI  - Moderate chronic kidney disease and cognitive function in adults 20 to 59 years
      of age: Third National Health and Nutrition Examination Survey (NHANES III).
AB  - Previous studies among elderly suggest an association between chronic kidney
      disease (CKD) and cognitive impairment. The purpose of this study was to
      determine whether moderate CKD is associated with cognitive performance among
      young, healthy, ethnically diverse adults. Three computerized cognitive function
      tests of visual-motor reaction time (Simple Reaction Time), visual attention
      (Symbol Digit Substitution), and learning/concentration (Serial Digit Learning)
      were administered to a random sample of participants, aged 20 to 59 yr, who
      completed initial interviews and medical examination in the Third National Health
      and Nutrition Examination Survey (NHANES III). Participants for this study (n =
      4849) completed at least one cognitive function test. GFR was estimated using the
      Modification of Diet in Renal Disease (MDRD) equation. Moderate CKD was defined
      as estimated GFR (eGFR) 30 to 59 ml/min per 1.73 m(2). Unadjusted, residual
      adjusted, and multivariate-adjusted logistic regression models were used. The
      cohort was 49.0% male and 11.6% black, and median (interquartile range) age was
      36 yr (27 to 45) and eGFR was 107.9 ml/min per 1.73 m(2) (95.0 to 125.4). There
      were 31 (0.8%) prevalent cases of moderate CKD. Models were adjusted for residual
      effects of age, gender, race, diabetes, and other known potential confounders. In
      multivariate models, moderate CKD was not significantly associated with reaction
      time but was significantly associated with poorer learning/concentration (odds
      ratio 2.41; 95% confidence interval 1.30 to 5.63) and impairment in visual
      attention (odds ratio 2.74; 95% confidence interval 1.01 to 7.40). In summary,
      among those in a large nationally representative sample of healthy, ethnically
      diverse 20- to 59-yr-old adults, moderate CKD, reflected by eGFR 30 to 59 ml/min
      per 1.73 m(2), was significantly associated with poorer performance in visual
      attention and learning/concentration.

PMID- 17554149
TI  - Flow-induced [Ca2+]i increase depends on nucleotide release and subsequent
      purinergic signaling in the intact nephron.
AB  - Flow induces cytosolic Ca(2+) increases ([Ca(2+)](i)) in intact renal tubules,
      but the mechanism is elusive. Mechanical stimulation in general is known to
      promote release of nucleotides (ATP/UTP) and trigger auto- and paracrine
      activation of P2 receptors in renal epithelia. It was hypothesized that the flow
      induced [Ca(2+)](i) response in the renal tubule involves mechanically stimulated
      nucleotide release. This study investigated (1) the expression of P2 receptors in
      mouse medullary thick ascending limb (mTAL) using P2Y(2) receptor knockout (KO)
      mice, (2) whether flow increases induce [Ca(2+)](i) elevations in mTAL, and (3)
      whether this flow response is affected in mice that are deplete of the main
      purinergic receptor. [Ca(2+)](i) was imaged in perfused mTAL with fura-2 or fluo
      4. It is shown that luminal and basolateral P2Y(2) receptors are the main
      purinergic receptor in this segment. Moreover, the data suggest presence of
      basolateral P2X receptors. Increases of tubular flow were imposed by promptly
      rising the inflow pressure, which triggered a marked increase of [Ca(2+)](i).
      This [Ca(2+)](i) response was significantly reduced in P2Y(2) receptor KO tubules
      (fura-2 ratio increase WT 0.44 +/- 0.09 [n = 28] versus KO 0.16 +/- 0.04 [n =
      13]). Furthermore, the flow response was greatly inhibited with luminal and
      basolateral scavenging of extracellular ATP (apyrase 7.5 U/ml) or blockage of P2
      receptors (suramin 300 microM). The flow response could still be elicited in the
      absence of extracellular Ca(2+). These results strongly suggest that increase of
      tubular flow elevates [Ca(2+)](i) in intact renal epithelia. This flow response
      is caused by release of bilateral nucleotides and subsequent activation of P2
      receptors.

PMID- 17554150
TI  - The continuous erythropoietin receptor activator affects different pathways of
      diabetic renal injury.
AB  - This study explored the tissue-protective properties of the continuous
      erythropoietin receptor activator (CERA) in an experimental model of
      (nonischemic) diabetic kidney injury (i.e., the db/db mouse). Mice were randomly
      treated with placebo (n = 25), low-dosage CERA (n = 25), and high-dosage CERA (n
      = 25). Also studied were 25 nondiabetic db/m mice. Hematocrit was comparable in
      placebo and low-dosage CERA-treated mice but increased significantly with high
      dosage CERA (P < 0.01 versus both). Significantly reduced expression of TGF-beta,
      vascular endothelial growth factor, and collagen IV was found in glomeruli and
      the tubulointerstitial area with CERA treatment, and these beneficial molecular
      effects were clearly dosage dependent (both P < 0.05 versus placebo). Similarly,
      CERA treatment caused a dosage-dependent increase in p-Akt, nephrin, and perlecan
      tissue expression (all P < 0.05 versus placebo). However, the accelerated
      mesangial expansion that was observed in placebo-treated db/db mice (versus db/m
      controls) was significantly reduced only in low-dosage CERA-treated mice (P <
      0.01). Moreover, albuminuria was significantly reduced in low- but not high
      dosage CERA-treated mice compared with placebo treatment (P < 0.05). In an
      ancillary study, phlebotomy was performed in high-dosage CERA-treated db/db mice
      to keep hematocrit within normal (baseline) levels. This procedure resulted in
      significantly (P < 0.05) less albuminuria as compared with high-dosage CERA
      treated mice without phlebotomy, thus preserving the tissue-protective potential
      of CERA. Long-term CERA treatment has beneficial dosage-dependent effects on
      molecular pathways of diabetic kidney damage. Low-dosage CERA does not affect
      hematocrit and therefore may be a feasible method of tissue protection in this
      setting.

PMID- 17554151
TI  - Increased expression of vascular endothelial growth factor in kidney leads to
      progressive impairment of glomerular functions.
AB  - Vascular endothelial growth factor (VEGF) is an important mediator in maintaining
      normal kidney functions. In addition, several lines of evidence suggest that
      upregulation of VEGF in glomeruli may be associated with or cause renal
      dysfunction such as diabetic nephropathy. For elucidation of the pathologic
      consequences of high levels of VEGF in glomeruli, transgenic (Tg) rabbits that
      express human VEGF(165) isoform in both kidney and liver under the control of the
      human alpha-1-antitrypsin promoter were generated and characterized. With the use
      of heterozygous Tg rabbits and their littermates aged 8 to 55 wk, renal functions
      and structures were investigated. Compared with control rabbits, Tg rabbits
      exhibited progressive proteinuria with increased GFR at the early stage and
      decreased GFR at the later stage. Histologic examinations revealed that Tg rabbit
      kidneys were characterized by considerable glomerular hypertrophy as a result of
      increased proliferation of both glomerular capillaries and mesangial cells
      accompanied by prominent podocyte hypertrophy. With increasing age starting from
      20 wk, Tg rabbit kidneys showed prominent formation of microaneurysms and
      capillary proliferation at the vascular pole area. At a later stage (55 wk), many
      glomeruli showed sclerosis and tuft collapse with the formation of glomerular
      cysts on a background of tubular atrophy and interstitial fibrosis. This study
      provides the first evidence that increased expression of VEGF in glomeruli
      directly causes the glomerular hypertrophy that is associated with proteinuria,
      suggesting that VEGF exerts multiple effects on the glomerular pathophysiologic
      processes.

PMID- 17554152
TI  - Thoughts on a hyperbolic curve.

PMID- 17554153
TI  - Validation of the Physical Activity Questionnaire for Older Children in children
      of different races.
AB  - The Physical Activity Questionnaire for Older Children (PAQ-C) is a validated
      self-report measure of physical activity widely used to assess physical activity
      in children (8-14 years of age). To date, however, the instrument has been
      validated in largely White Canadian samples. The purpose of the present article
      is to determine the psychometric properties of the PAQ-C for African American,
      European American, and Hispanic children. Two studies were conducted in which
      independent samples were administered the PAQ-C, along with varying indices of
      cardiovascular fitness, fatness, and psychological measures related to physical
      activity. Results showed that the reliability and validity of the PAQ-C varied by
      race and that modifications might be necessary.

PMID- 17554154
TI  - Developmental coordination disorder and cardiorespiratory fitness in children.
AB  - It is not known whether children with Developmental Coordination Disorder (DCD)
      have lower cardiorespiratory fitness (CRF) than children without the disorder, or
      whether this relationship varies by age and gender. These issues are examined
      using a cross-sectional assessment of children 9-14 years of age (N = 549).
      Participants were screened for DCD using the short form Bruininks-Oseretsky Test
      of Motor Proficiency (BOTMP-SF). A BOTMP-SF age-adjusted standard score at or
      below the 10th percentile rank on the BOTMP-SF was required to classify a
      diagnosis for probable DCD. CRF was determined from each participant's predicted
      peak-aerobic power using the Leger 20-m shuttle-run test. Children with DCD
      report lower CRF than children without the disorder and are more likely to be in
      a high-risk group (<or= 20th percentile in peak VO2). Moreover, 70% of boys with
      DCD scored at or below the 20th percentile in peak VO2. Further research in a
      laboratory setting should be conducted to confirm these findings.

PMID- 17554155
TI  - The effect of feedback and information on children's pedometer step counts at
      school.
AB  - This study examined whether feedback or feedback plus physical activity
      information could increase the number of pedometer steps taken during 1 school
      week. One hundred seventy-seven students (mean age 9.124 +/- 1.11 years) in three
      elementary schools participated. Schools were randomly assigned to control (CON),
      feedback (FB), or feedback plus information (FB+I) groups. Children wore
      pedometers during school time for 5 consecutive weekdays. The total steps of the
      groups were recorded at the end of each school day, with students in the FB and
      FB+I groups free to view their step counts. In addition, the FB+I group received
      information and ideas about how they could increase their daily steps. The CON
      group received no step-count feedback or information. Students in the FB+I group
      achieved significantly more steps per minute (17.17 +/- 4.87) than those in the
      FB (13.77 +/- 4.06, p = 0.003) and CON (12.41 +/- 3.12, p = 0.0001) groups.
      Information, as well as step-count feedback, increased elementary students'
      school-based physical activity (number of steps) in the short term. A longer
      intervention period is necessary to assess the sustained impact of this type of
      approach.

PMID- 17554156
TI  - Precompetitive state anxiety, objective and subjective performance, and causal
      attributions in competitive swimmers.
AB  - This study investigated the nature of the relationship between precompetitive
      state anxiety (CSAI-2C), subjective (race position) and objective (satisfaction)
      performance outcomes, and self-rated causal attributions (CDS-IIC) for
      performance in competitive child swimmers. Race position, subjective
      satisfaction, self-confidence, and, to a lesser extent, cognitive state anxiety
      (but not somatic state anxiety) were associated with the attributions provided by
      the children for their swimming performance. The study partially supported the
      self-serving bias hypothesis; winners used the ego-enhancing attributional
      strategy, but the losers did not use an ego-protecting attributional style. Age
      but not gender appeared to influence the attributions provided in achievement
      situations.

PMID- 17554157
TI  - Tracking physical activity and sedentary behavior in young children.
AB  - Tracking of total physical activity (PA), moderate to vigorous activity (MVPA),
      and sedentary behavior was assessed in 42 young children (mean age at baseline
      3.8 years) over a 2-year period using the Actigraph accelerometer. Tracking was
      analyzed using Spearman rank correlations, percentage agreements, and kappa
      statistics. Spearman rank correlations were r = .35 (p = .002) for total PA, r =
      .37 (p = .002) for MVPA, and r = .35 (p = .002) for sedentary behavior.
      Percentage agreements for PA, MVPA, and sedentary behavior were 38, 41, and 26
      respectively. Kappa statistics for PA, MVPA, and sedentary behavior ranged from
      poor to fair. Results suggest low levels of tracking of total physical activity,
      MVPA, and sedentary behavior in young Scottish children over a 2-year period.

PMID- 17554158
TI  - A movement-analysis comparison in two models of junior sport.
AB  - Despite widespread encouragement for children to participate in sport, the
      efficacy of early sporting pathways remains underexplored. We compared a
      rotational junior-sport model combining skills from rugby, cricket, and netball
      with a modified games model. Motion analysis was used to quantify movement.
      Results revealed no differences between sporting models in relative percent time
      spent stationary (p = .32), walking (p = .89), jogging (p = .45), and fast
      running (p = .06). The rotational model had a greater number of skill-development
      opportunities per minute (median = 3.4) compared with the modified games model
      (median = 1.1, p = .001). Promising results from varied and rotational skill
      exposure warrant further elucidation.

PMID- 17554159
TI  - Analysis of swimming performance from physical, physiological, and biomechanical
      parameters in young swimmers.
AB  - The purpose of this study was to examine the influence of the energy cost of
      swimming, body composition, and technical parameters on swimming performance in
      young swimmers. Twenty-nine swimmers, 15 prepubertal (11.9 +/- 0.3 years; Tanner
      Stages 1-2) and 14 pubertal (14.3 +/- 1.4 years; Tanner Stages 3-4) boys
      participated in the study. The energy cost of swimming (Cs) and stroking
      parameters were assessed over maximal 400-m front-crawl swimming in a 25-m
      swimming pool. The backward extrapolation technique was used to evaluate peak
      oxygen consumption (VO2peak). A stroke index (SI; m2 . s(-1) . cycles(-1)) was
      calculated by multiplying the swimming speed by the stroke length. VO2peak
      results were compared with VO2peak test in the laboratory (bicycle, 2.86 +/- 0.74
      L/min, vs. in water, 2.53 +/- 0.50 L/min; R2 = .713; p = .0001). Stepwise
      regression analyses revealed that SI (R2 = .898), in-water VO2peak (R2 = .358),
      and arm span (R2 = .454) were the best predictors of swimming performance. The
      backward-extrapolation method could be used to assess VO2peak in young swimmers.
      SI, arm span, and VO2peak appear to be the major determinants of front-crawl
      swimming performance in young swimmers.

PMID- 17554160
TI  - Aerobic-exercise training improves ventilatory efficiency in overweight children.
AB  - The objective of this study was to investigate the effect of an 8-week aerobic
      exercise training program on ventilatory threshold and ventilatory efficiency in
      overweight children. Twenty overweight children (BMI > 85th percentile) performed
      a graded cycle exercise test at baseline and were then randomly assigned to 8
      weeks of stationary cycling (n = 10) or a nonexercising control group (n = 10).
      Ventilatory variables were examined at ventilatory threshold (VT), which was
      determined via the Dmax method. After 8 weeks, significant improvements occurred
      in the exercise group compared with the control group for oxygen uptake at VT
      (exercise = 1.03 +/- 0.13 to 1.32 +/- 0.12 L/min vs. control = 1.20 +/- 0.10 to
      1.11 +/- 0.10 L/min, p < .05) and ventilatory equivalent of carbon dioxide
      (VE/VCO2) at VT (exercise = 32.8 +/- 0.80 to 31.0 +/- 0.53 vs. control = 30.3 +/-
      0.88 to 31.7 +/- 0.91, p < .05). Aerobic-exercise training might help reverse the
      decrements in cardiopulmonary function observed over time in overweight children.

PMID- 17554161
TI  - Relationship of fitness, fatness, and coronary-heart-disease risk factors in 12-
      to 13-year-olds.
AB  - The purpose of this study was to examine relationships between aerobic fitness
      (AF), fatness, and coronary-heart-disease (CHD) risk factors in 12- to 13-year
      olds. The data were obtained from 208 schoolchildren (100 boys; 108 girls) ages
      12.9 +/- 0.3 years. Measurements included AF, indices of obesity, blood pressure,
      blood lipids and lipoproteins, fibrinogen, homocysteine, and C-reactive protein.
      An inverse relationship was found between AF and fatness (p <or= .05). Fatness
      was related to a greater number of CHD risk factors than fitness was (p <or=
      .05). Further analysis revealed fatness to be an independent predictor of
      triglyceride and blood-pressure levels (p <or= .05). Our findings indicate that,
      for young people, fatness rather than fitness is independently related to CHD
      risk factors.

PMID- 17554162
TI  - Purification, crystallization and structure determination of native GroEL from
      Escherichia coli lacking bound potassium ions.
AB  - GroEL is a member of the ATP-dependent chaperonin family that promotes the proper
      folding of many cytosolic bacterial proteins. The structures of GroEL in a
      variety of different states have been determined using X-ray crystallography and
      cryo-electron microscopy. In this study, a 3.02 A crystal structure of the native
      GroEL complex from Escherichia coli is presented. The complex was purified and
      crystallized in the absence of potassium ions, which allowed evaluation of the
      structural changes that may occur in response to cognate potassium-ion binding by
      comparison to the previously determined wild-type GroEL structure (PDB code
      1xck), in which potassium ions were observed in all 14 subunits. In general, the
      structure is similar to the previously determined wild-type GroEL crystal
      structure with some differences in regard to temperature-factor distribution.

PMID- 17554163
TI  - New insights into the binding mode of coenzymes: structure of Thermus
      thermophilus Delta1-pyrroline-5-carboxylate dehydrogenase complexed with NADP+.
AB  - Delta(1)-Pyrroline-5-carboxylate dehydrogenase (P5CDh) is known to preferentially
      use NAD(+) as a coenzyme. The k(cat) value of Thermus thermophilus P5CDh
      (TtP5CDh) is four times lower for NADP(+) than for NAD(+). The crystal structure
      of NADP(+)-bound TtP5CDh was solved in order to study the structure-activity
      relationships for the coenzymes. The binding mode of NADP(+) is essentially
      identical to that in the previously solved NAD(+)-bound form, except for the
      regions around the additional 2'-phosphate group of NADP(+). The coenzyme-binding
      site can only accommodate this group by the rotation of a glutamate residue and
      subtle shifts in the main chain. The 2'-phosphate of NADP(+) increases the number
      of hydrogen bonds between TtP5CDh and NADP(+) compared with that between TtP5CDh
      and NAD(+). Furthermore, the phosphate of the bound NADP(+) would restrict the
      ;bending' of the coenzyme because of steric hindrance. Such bending is important
      for dissociation of the coenzymes. These results provide a plausible explanation
      of the lower turnover rate of NADP(+) compared with NAD(+).

PMID- 17554164
TI  - Structure of 1-deoxy-D-xylulose 5-phosphate reductoisomerase in a quaternary
      complex with a magnesium ion, NADPH and the antimalarial drug fosmidomycin.
AB  - The crystal structure of 1-deoxy-D-xylulose 5-phosphate reductoisomerase (DXR)
      from Escherichia coli complexed with Mg(2+), NADPH and fosmidomycin was solved at
      2.2 A resolution. DXR is the key enzyme in the 2-C-methyl-D-erythritol 4
      phosphate pathway and is an effective target of antimalarial drugs such as
      fosmidomycin. In the crystal structure, electron density for the flexible loop
      covering the active site was clearly observed, indicating the well ordered
      conformation of DXR upon substrate binding. On the other hand, no electron
      density was observed for the nicotinamide-ribose portion of NADPH and the
      position of Asp149 anchoring Mg(2+) was shifted by NADPH in the active site.

PMID- 17554165
TI  - Alternative cyanide-binding modes to the haem iron in haem oxygenase.
AB  - Cyanide is a well known potent inhibitor of haem proteins, including haem
      oxygenase (HO). Generally, cyanide coordinates to the ferric haem iron with a
      linear binding geometry; the Fe-C-N angle ranges from 160 to 180 degrees . The Fe
      C-N angle observed in the crystal structure of haem-HO bound to cyanide prepared
      at alkaline pH was 166 degrees . Here, it is reported that cyanide can bind to
      the haem iron in HO in a bent mode when the ternary complex is prepared at
      neutral pH; a crystal structure showed that the Fe-C-N angle was bent by 47
      degrees . Unlike the ternary complex prepared at alkaline pH, in which the haem
      group, including the proximal ligand and the distal helix, was displaced upon
      cyanide binding, the positions of the haem group and the distal helix in the
      complex prepared at neutral pH were nearly identical to those in haem-HO. Cyanide
      that was bound to haem-HO with a bent geometry was readily photodissociated,
      whereas that bound with a linear geometry was not photodissociated. Thus,
      alternative cyanide-binding modes with linear and bent geometries exist in the
      crystalline state of haem-HO.

PMID- 17554166
TI  - Crystallization and crystal properties of squid rhodopsin.
AB  - Rhodopsin, a photoreceptor membrane protein in the retina, is a prototypical
      member of the G-protein-coupled receptor family. In this study, rhodopsin from
      the retina of the squid Todarodes pacificus was treated with V8 protease to
      remove the C-terminal extension. Truncated rhodopsin was selectively extracted
      from the microvillar membranes using alkyl glucoside in the presence of zinc ions
      and was then crystallized by the sitting-drop vapour-diffusion method. Of the
      various crystals obtained, hexagonal crystals grown in the presence of
      octylglucoside and ammonium sulfate diffracted to 2.8 A resolution. The
      diffraction data suggested that the crystal belongs to space group P6(2), with
      unit-cell parameters a = b = 122.1, c = 158.6 A. Preliminary crystallographic
      analysis, together with linear dichroism results, suggested that the rhodopsin
      dimers are packed in such a manner that their transmembrane helices are aligned
      nearly parallel to the c axis.

PMID- 17554167
TI  - Expression, purification, cocrystallization and preliminary crystallographic
      analysis of sucrose octasulfate/human complement regulator factor H SCRs 6-8.
AB  - Human plasma protein complement factor H (FH) is an inhibitor of the
      spontaneously activated alternative complement pathway. An allotypic variant of
      FH, 402His, has been associated with age-related macular degeneration, the
      leading cause of blindness in the elderly. Crystals of FH domains 6-8 (FH678)
      containing 402His have been grown in the presence of a polyanionic sucrose
      octasulfate ligand (an analogue of the natural glycosaminoglycan ligands of FH)
      using both native and selenomethionine-derivatized protein. Native data sets
      diffracting to 2.3 A and SeMet data sets of up to 2.8 A resolution have been
      collected. An anomalous difference Patterson map reveals self- and cross-peaks
      from two incorporated Se atoms. The corresponding selenium substructure has been
      solved.

PMID- 17554168
TI  - Expression, crystallization and preliminary X-ray diffraction studies of
      recombinant Clostridium perfringens beta 2-toxin.
AB  - Clostridium perfringens is a Gram-positive sporulating anaerobic bacterium that
      is responsible for a wide spectrum of diseases in animals, birds and humans. The
      virulence of C. perfringens is associated with the production of several
      enterotoxins and exotoxins. beta2-toxin is a 28 kDa exotoxin produced by C.
      perfringens. It is implicated in necrotic enteritis in animals and humans, a
      disease characterized by a sudden acute onset with lethal hemorrhagic mucosal
      ulceration. The recombinant expression, purification and crystallization of beta2
      toxin using the batch-under-oil technique are reported here. Native X-ray
      diffraction data were obtained to 2.9 A resolution on a synchrotron beamline at
      the F2 station at Cornell High Energy Synchrotron Source (CHESS) using an ADSC
      Quantum-210 CCD detector. The crystals belong to space group R3, with a dimer in
      the asymmetric unit; the unit-cell parameters are a = b = 103.71, c = 193.48 A,
      alpha = beta = 90, gamma = 120 degrees using the hexagonal axis setting. A self
      rotation function shows that the two molecules are related by a
      noncrystallographic twofold axis with polar angles omega = 90.0, phi = 210.3
      degrees.

PMID- 17554169
TI  - Purification, crystallization and data collection of methicillin-resistant
      Staphylococcus aureus Sar2676, a pantothenate synthetase.
AB  - Sar2676, a pantothenate synthetase with a molecular weight of 31 419 Da from
      methicillin-resistant Staphylococcus aureus, has been expressed, purified and
      crystallized at 293 K. The protein crystallizes in a primitive triclinic lattice,
      with unit-cell parameters a = 45.3, b = 60.5, c = 117.6 A, alpha = 87.2, beta =
      81.2, gamma = 68.4 degrees . A complete data set has been collected to 2.3 A
      resolution at the ESRF. Consideration of the likely solvent content suggested the
      asymmetric unit to contain four molecules. This has been confirmed by molecular
      replacement phasing calculations, which give a solution with four monomers using
      a monomer of pantothenate synthetase from Escherichia coli (PDB code 1iho), which
      is 41% identical to Sar2676, as a search model.

PMID- 17554170
TI  - Purification, crystallization and preliminary X-ray crystallographic analysis of
      branched-chain aminotransferase from Deinococcus radiodurans.
AB  - The branched-chain amino-acid aminotransferase (BCAT), which requires pyridoxal
      5'-phosphate (PLP) as a cofactor, is a key enzyme in the biosynthetic pathway of
      the hydrophobic amino acids leucine, isoleucine and valine. DrBCAT from
      Deinococcus radiodurans, which has a molecular weight of 40.9 kDa, was
      crystallized using the hanging-drop vapour-diffusion method. According to X-ray
      diffraction data to 2.50 A resolution from a DrBCAT crystal, the crystal belongs
      to space group P2(1)2(1)2(1), with unit-cell parameters a = 56.37, b = 90.70, c =
      155.47 A. Preliminary analysis indicates the presence of two DrBCAT molecules in
      the asymmetric unit, with a solvent content of 47.52%.

PMID- 17554171
TI  - Improved crystallization of the coxsackievirus B3 RNA-dependent RNA polymerase.
AB  - The Picornaviridae virus family contains a large number of human pathogens such
      as poliovirus, hepatitis A virus and rhinoviruses. Amongst the viruses belonging
      to the genus Enterovirus, several serotypes of coxsackievirus coexist for which
      neither vaccine nor therapy is available. Coxsackievirus B3 is involved in the
      development of acute myocarditis and dilated cardiomyopathy and is thought to be
      an important cause of sudden death in young adults. Here, the first crystal of a
      coxsackievirus RNA-dependent RNA polymerase is reported. Standard crystallization
      methods yielded crystals that were poorly suited to X-ray diffraction studies,
      with one axis being completely disordered. Crystallization was improved by
      testing crystallization solutions from commercial screens as additives. This
      approach yielded crystals that diffracted to 2.1 A resolution and that were
      suitable for structure determination.

PMID- 17554172
TI  - Crystallization and preliminary X-ray diffraction studies of the ferredoxin
      reductase component in the Rieske nonhaem iron oxygenase system carbazole 1,9a
      dioxygenase.
AB  - Carbazole 1,9a-dioxygenase (CARDO), which consists of an oxygenase component
      (CARDO-O) and the electron-transport components ferredoxin (CARDO-F) and
      ferredoxin reductase (CARDO-R), catalyzes dihydroxylation at the C1 and C9a
      positions of carbazole. CARDO-R was crystallized at 277 K using the hanging-drop
      vapour-diffusion method with the precipitant PEG 8000. Two crystal types (types I
      and II) were obtained. The type I crystal diffracted to a maximum resolution of
      2.80 A and belonged to space group P4(2)2(1)2, with unit-cell parameters a = b =
      158.7, c = 81.4 A. The type II crystal was obtained in drops from which type I
      crystals had been removed; it diffracted to 2.60 A resolution and belonged to the
      same space group, with unit-cell parameters a = b = 161.8, c = 79.5 A.

PMID- 17554173
TI  - Crystallization and preliminary X-ray analysis of the complex between a Bacillus
      subtilis alpha/beta-type small acid-soluble spore protein and DNA.
AB  - An engineered variant of an alpha/beta-type small acid-soluble spore protein
      (SASP) from Bacillus subtilis was crystallized in a complex with a ten-base-pair
      double-stranded DNA by the hanging-drop vapor-diffusion method using ammonium
      sulfate as a precipitating agent. Crystals grew at 281 K using sodium cacodylate
      buffer pH 5.5 and these crystals diffracted X-rays to beyond 2.4 A resolution
      using synchrotron radiation. The crystallized complex contains two or three SASP
      molecules bound to one DNA molecule. The crystals belong to the hexagonal space
      group P6(1)22 or P6(5)22, with unit-cell parameters a = b = 87.0, c = 145.4 A,
      alpha = beta = 90.0, gamma = 120.0 degrees. Diffraction data were 96.6% complete
      to 2.4 A resolution, with an R(sym) of 8.5%. Structure solution by the
      multiwavelength/single-wavelength anomalous dispersion method using isomorphous
      crystals of selenomethionine-labeled protein is in progress.

PMID- 17554174
TI  - Reductive methylation to improve crystallization of the putative oxidoreductase
      Rv0765c from Mycobacterium tuberculosis.
AB  - Rv0765c from Mycobacterium tuberculosis was cloned and heterologously expressed
      in Escherichia coli. It was purified using affinity and size-exclusion
      chromatographic techniques and crystallized. The native protein crystallized in a
      hexagonal crystal form which diffracted to 7 A resolution. In an attempt to
      improve the quality of the Rv0765c crystals, the protein was modified by
      reductive methylation using dimethylaminoborane and formaldehyde. The modified
      protein crystallized under different conditions in a tetragonal crystal form,
      from which diffraction data could be collected to a resolution of 3.2 A. In both
      crystal forms of Rv0765c, the asymmetric unit contained two copies of the protein
      molecule.

PMID- 17554175
TI  - Crystallization and preliminary crystallographic analysis of cysteine synthase
      from Entamoeba histolytica.
AB  - Entamoeba histolytica, the causative agent of human amoebiasis, is essentially
      anaerobic, requiring a small amount of oxygen for growth. It cannot tolerate the
      higher concentration of oxygen present in human tissues or blood. However, during
      tissue invasion it is exposed to a higher level of oxygen, leading to oxygen
      stress. Cysteine, which is a vital thiol in E. histolytica, plays an essential
      role in its oxygen-defence mechanisms. The major route of cysteine biosynthesis
      in this parasite is the condensation of O-acetylserine with sulfide by the de
      novo cysteine-biosynthetic pathway, which involves cysteine synthase (EhCS) as a
      key enzyme. In this study, EhCS was cloned, expressed in Escherichia coli and
      purified by affinity and size-exclusion chromatography. The purified protein was
      crystallized in space group P4(1) with two molecules per asymmetric unit and a
      complete data set was collected to a resolution of 1.86 A. A molecular
      replacement solution was obtained using the Salmonella typhimurium O-acetylserine
      sulfhydrylase structure as a probe and had a correlation coefficient of 37.7% and
      an R factor of 48.8%.

PMID- 17554176
TI  - Heterodimeric nitrate reductase (NapAB) from Cupriavidus necator H16:
      purification, crystallization and preliminary X-ray analysis.
AB  - The periplasmic nitrate reductase from Cupriavidus necator (also known as
      Ralstonia eutropha) is a heterodimer that is able to reduce nitrate to nitrite.
      It comprises a 91 kDa catalytic subunit (NapA) and a 17 kDa subunit (NapB) that
      is involved in electron transfer. The larger subunit contains a molybdenum active
      site with a bis-molybdopterin guanine dinucleotide cofactor as well as one [4Fe
      4S] cluster, while the small subunit is a di-haem c-type cytochrome. Crystals of
      the oxidized form of this enzyme were obtained using polyethylene glycol 3350 as
      precipitant. A single crystal grown at the High Throughput Crystallization
      Laboratory of the EMBL in Grenoble diffracted to beyond 1.5 A at the ESRF (ID14
      1), which is the highest resolution reported to date for a nitrate reductase. The
      unit-cell parameters are a = 142.2, b = 82.4, c = 96.8 A, beta = 100.7 degrees,
      space group C2, and one heterodimer is present per asymmetric unit.

PMID- 17554177
TI  - Crystallization and preliminary X-ray analysis of the electron-transfer complex
      of Rieske-type [2Fe-2S] ferredoxin and NADH-dependent ferredoxin reductase
      derived from Acidovorax sp. strain KKS102.
AB  - The electron-transfer complex of BphA3, a Rieske-type [2Fe-2S] ferredoxin, and
      BphA4, a NADH-dependent ferredoxin reductase, was crystallized using the sitting
      drop vapour-diffusion method under anaerobic conditions. The obtained crystals
      were analyzed by SDS-PAGE, which showed that they contained both BphA3 and BphA4.
      The crystals belong to space group P2(1), with unit-cell parameters a = 60.60, b
      = 173.72, c = 60.98 A, beta = 115.8 degrees, and diffracted to a resolution of
      1.9 A.

PMID- 17554178
TI  - Crystallization and preliminary X-ray diffraction of the Munc18c-syntaxin4 (1-29)
      complex.
AB  - The production of diffraction-quality crystals of Munc18c, a protein involved in
      regulating vesicular exocytosis in mammals, is reported. The diffraction
      resolution of Munc18c crystals was optimized by (i) cocrystallizing with a
      peptide fragment of the Munc18c functional binding partner syntaxin4, (ii) using
      nanolitre free-interface diffusion crystallization-screening chips and microlitre
      hanging-drop vapour diffusion and (iii) applying a post-crystallization
      dehydration treatment. Crystals belonging to the cubic space group P2(1)3, with
      unit-cell parameters a = b = c = 170.8 A, alpha = beta = gamma = 90 degrees ,
      were generated that diffract to 3.7 A resolution on a laboratory X-ray source.

PMID- 17554179
TI  - Crystallization and preliminary X-ray crystallographic studies of the axin DIX
      domain.
AB  - Axin is a negative regulator of the canonical Wnt signalling pathway that
      mediates the phosphorylation of beta-catenin by glycogen synthase kinase 3beta.
      The DIX domain of rat axin, which is important for its homooligomerization and
      interactions with other regulators in the Wnt pathway, was purified and
      crystallized by the sitting-drop vapour-diffusion technique using polyethylene
      glycol 6000 and lithium sulfate as crystallization agents. Crystals belong to
      space group P6(1) or P6(5), with unit-cell parameters a = b = 91.49, c = 84.92 A.
      An X-ray diffraction data set has been collected to a nominal resolution of 2.9
      A.

PMID- 17554180
TI  - Crystallization and preliminary X-ray analysis of PH1010 from Pyrococcus
      horikoshii OT3, a member of the archaeal DUF54 family of proteins.
AB  - PH1010 from Pyrococcus horikoshii OT3, a member of the archaeal DUF54 family of
      proteins, was expressed, purified and crystallized. Crystallization was performed
      by the sitting-drop vapour-diffusion method using PEG 3350 as the precipitant.
      The crystal diffracted X-rays to 1.90 A resolution using a synchrotron-radiation
      source. The space group of the crystal was determined to be P2(1)2(1)2(1), with
      unit-cell parameters a = 46.9, b = 49.5, c = 132.7 A. The crystal contained two
      PH1010 molecules in the asymmetric unit (V(M) = 2.4 A(3) Da(-1)) and had a
      solvent content of 48%.

PMID- 17554181
TI  - Crystallization and preliminary X-ray analysis of the Ca2+-bound C-terminal lobe
      of troponin C in complex with a troponin I-derived peptide fragment from Akazara
      scallop.
AB  - Troponin C (TnC) is the Ca(2+)-binding component of troponin and triggers muscle
      contraction. TnC of the invertebrate Akazara scallop can bind only one Ca(2+) at
      the C-terminal EF-hand motif. Recombinant TnC was expressed in Escherichia coli,
      purified, complexed with a 24-residue synthetic peptide derived from scallop
      troponin I (TnI) and crystallized. The crystals diffracted X-rays to 1.80 A
      resolution and belonged to space group P2(1)2(1)2(1), with unit-cell parameters a
      = 32.1, b = 42.2, c = 60.0 A. The asymmetric unit was assumed to contain one
      molecular complex of the Akazara scallop TnC C-lobe and TnI fragment, with a
      Matthews coefficient of 1.83 A(3) Da(-1) and a solvent content of 33.0%.

PMID- 17554182
TI  - Crystallization and preliminary X-ray crystallographic studies of the [NiFe]
      hydrogenase maturation proteins HypC and HypD.
AB  - HypC and HypD proteins are required for the insertion of the Fe atom with
      diatomic ligands into the large subunit of [NiFe] hydrogenases, an important step
      in the maturation process of this type of hydrogenase. The crystallization and
      preliminary crystallographic analysis of HypC and HypD from Thermococcus
      kodakaraensis KOD1 are reported. Crystals of HypC grew in two different forms.
      Monoclinic crystals of HypC in space group C2 with unit-cell parameters a = 78.2,
      b = 59.1, c = 54.0 A, beta = 109.0 degrees were obtained using PEG 4000 and
      ammonium sulfate or sodium bromide as precipitants. They diffracted X-rays to 1.8
      A resolution and were suitable for structure determination. Crystals of HypD were
      also obtained in two different forms. The monoclinic crystals obtained using PEG
      4000 and magnesium chloride diffracted X-rays to beyond 2.1 A resolution, despite
      growing as clusters. They belong to space group P2(1), with unit-cell parameters
      a = 42.3, b = 118.4, c = 81.2 A, beta = 100.9 degrees , and are suitable for data
      collection.

PMID- 17554183
TI  - Crystallization and preliminary crystallographic characterization of the origin
      binding domain of the bacteriophage lambda O replication initiator.
AB  - The bacteriophage lambda O protein binds to the lambda replication origin
      (orilambda) and serves as the primary replication initiator for the viral genome.
      The binding energy derived from the binding of O to orilambda is thought to help
      drive DNA opening to facilitate initiation of DNA replication. Detailed
      understanding of this process is severely limited by the lack of high-resolution
      structures of O protein or of any lambdoid phage-encoded paralogs either with or
      without DNA. The production of crystals of the origin-binding domain of lambda O
      that diffract to 2.5 A is reported. Anomalous dispersion methods will be used to
      solve this structure.

PMID- 17554184
TI  - Diffusion-weighted imaging with sensitivity encoding (SENSE) for detecting
      cranial bone marrow metastases: comparison with T1-weighted images.
AB  - OBJECTIVE: This study was designed to determine whether diffusion-weighted
      imaging (DWI) with sensitivity encoding (SENSE) could detect bone marrow
      involvement in patients with cranial bone marrow (CBM) metastases. DWI results
      obtained were compared with T1-weighted imaging (T1WI) findings. MATERIALS AND
      METHODS: DWI with sensitivity encoding (SENSE; b value = 1,000) was performed
      consecutively in 13 patients with CBM metastases diagnosed pathologically and
      radiologically. CBM lesions were dichotomized according to the involved site,
      i.e., skull base or calvarium. Two radiologists qualitatively evaluated the
      relative conspicuousness of CBM lesions and image qualities in B0 and in
      isotropic DWI and in T1WI. According to region of interest analysis of normal and
      pathologic marrow for these three sequences, absolute signal difference
      percentages (SD%) were calculated to quantitatively analyze lesion contrast.
      RESULTS: All 20 lesions in 13 patients with CBM metastases revealed abnormal DWI
      signals in areas corresponding to T1WI abnormalities. Both skull base and
      calvarial lesions provided better lesion conspicuousness than T1WI and B0 images.
      Although the image quality of DWI was less satisfactory than that of T1WI,
      relatively good image qualities were obtained. Quantitatively, B0 images (SD%,
      82.1 +/- 7.9%) showed better lesion contrast than isotropic DWI (SD%, 71.4 +/-
      13.7%) and T1WI (SD%, 65.7 +/- 9.3%) images. CONCLUSION: For scan times of less
      than 30 seconds, DWI with SENSE was able to detect bone marrow involvement, and
      was superior to T1WI in terms of lesion conspicuity. DWI with SENSE may be
      helpful for the detection of cranial bone/bone marrow metastases when used in
      conjunction with conventional MR sequences.

PMID- 17554185
TI  - Evaluating the degree of conformity of papillary carcinoma and follicular
      carcinoma to the reported ultrasonographic findings of malignant thyroid tumor.
AB  - OBJECTIVE: We wanted to evaluate the degree of conformity of papillary carcinoma
      and follicular carcinoma to the reported ultrasonographic findings of malignant
      thyroid tumor. MATERIALS AND METHODS: Between January 2003 and December 2004,
      fine needle aspiration biopsy was performed in 1,036 patients with palpable and
      nonpalpable thyroid lesions. We retrospectively reviewed the ultrasonographic
      findings of patients with papillary carcinomas (n = 127) and follicular
      carcinomas (n = 23) that were proven by operation or fine needle aspiration
      biopsy. We analyzed the ultrasonographic findings of these nodules based on the
      reported ultrasonographic findings of malignant thyroid tumor: hypoechogenicity,
      a taller than wide orientation, a microlobulated or irregular margin, a thick
      hypoechoic rim (halo sign), microcalcification and cystic change. RESULTS: The
      echogenicity was hypoechoic in 72.4% (92/127) of the papillary carcinomas, but it
      was isoechoic in 65.2% (15/23) of the follicular carcinomas (p < 0.001). The
      nodule shape was tall or round in 74.1% of the papillary carcinomas, but it was
      flat in 72.7% of the follicular carcinomas (p < 0.001). The tumor margin was
      microlobulated or irregular in 92.9% of the papillary carcinomas and in 60.9% of
      the follicular carcinomas (p < 0.001). A hypoechoic rim was seen in 26% of the
      papillary carcinomas (thin rim: 13.4%, thick rim: 12.6%) and in 86.6% of the
      follicular carcinomas (thin rim: 39.1%, thick rim: 47.8%, p < 0.001).
      Microcalcifications were demonstrated in 33.9% of the papillary carcinomas and in
      none of the cases of follicular carcinoma (p < 0.001). A solid mass without
      cystic change were seen in 98.4% of the papillary carcinomas and in 82.6% of the
      follicular carcinomas (p < 0.001). CONCLUSION: The previously reported
      ultrasonography findings of malignant thyroid tumor are in conformity with most
      of the papillary carcinomas, but not with follicular carcinomas. The current
      ultrasonographic features for thyroid malignancy should be cautiously applied as
      the indication for needle aspiration biopsy so that follicular carcinomas are not
      missed by too narrow and strict biopsy criteria.

PMID- 17554186
TI  - Reproducibility of computer-aided detection marks in digital mammography.
AB  - OBJECTIVE: To evaluate the performance and reproducibility of a computeraided
      detection (CAD) system in mediolateral oblique (MLO) digital mammograms taken
      serially, without release of breast compression. MATERIALS AND METHODS: A CAD
      system was applied preoperatively to the fullfield digital mammograms of two MLO
      views taken without release of breast compression in 82 patients (age range: 33
      83 years; mean age: 49 years) with previously diagnosed breast cancers. The total
      number of visible lesion components in 82 patients was 101: 66 masses and 35
      microcalcifications. We analyzed the sensitivity and reproducibility of the CAD
      marks. RESULTS: The sensitivity of the CAD system for first MLO views was 71%
      (47/66) for masses and 80% (28/35) for microcalcifications. The sensitivity of
      the CAD system for second MLO views was 68% (45/66) for masses and 17% (6/35) for
      microcalcifications. In 84 ipsilateral serial MLO image sets (two patients had
      bilateral cancers), identical images, regardless of the existence of CAD marks,
      were obtained for 35% (29/84) and identical images with CAD marks were obtained
      for 29% (23/78). Identical images, regardless of the existence of CAD marks, for
      contralateral MLO images were 65% (52/80) and identical images with CAD marks
      were obtained for 28% (11/39). The reproducibility of CAD marks for the true
      positive masses in serial MLO views was 84% (42/50) and that for the true
      positive microcalcifications was 0% (0/34). CONCLUSION: The CAD system in digital
      mammograms showed a high sensitivity for detecting masses and
      microcalcifications. However, reproducibility of microcalcification marks was
      very low in MLO views taken serially without release of breast compression.
      Minute positional change and patient movement can alter the images and result in
      a significant effect on the algorithm utilized by the CAD for detecting
      microcalcifications.

PMID- 17554187
TI  - Sonographically-guided 14-gauge core needle biopsy for papillary lesions of the
      breast.
AB  - OBJECTIVE: We wanted to assess the need for surgical excising papillary lesions
      of the breast that were diagnosed upon sonographically guided 14-gauge core
      needle biopsy. MATERIALS AND METHODS: Sixty-nine women (age range: 25-74 years,
      mean age: 51.7 years) with 69 papillary lesions (4.9%) were diagnosed and
      followed after performing sonographically guided 14-gauge core needle biopsies.
      Surgical excision was performed for 44 (64%) of 69 papillary lesions, and 25
      lesions were followed with imaging studies (range: 6-46 months, mean: 17.9
      months). The histologic findings upon core biopsy were compared with the
      surgical, imaging and follow-up findings. RESULTS: Core needle biopsies of 69
      lesions yielded tissue that was classified as benign for 43 lesions, atypical for
      18 lesions and malignant for eight lesions. Of the 43 lesions that yielded benign
      papilloma upon core needle biopsy, one had intraductal papillary carcinoma found
      upon surgery. An immediate surgical biopsy was recommended for this lesion
      because of the imaging-histologic discordance. No additional carcinoma was found
      during the imaging follow-up. Surgical excision was performed for 17 atypical
      papillary lesions, and this revealed intraductal (n = 6) or invasive (n = 2)
      papillary carcinoma in 8 (47%) lesions. Of the seven intraductal papillary
      carcinomas, surgery revealed invasive papillary carcinoma in one (14%).
      CONCLUSION: Our results suggest that papillary lesions of the breast that are
      diagnosed as benign upon sonographically guided 14-gauge core needle biopsy can
      be followed when the results are concordant with the imaging findings.

PMID- 17554188
TI  - Chronic extrahepatic bile duct dilatation: sonographic screening in the patients
      with opioid addiction.
AB  - OBJECTIVE: One of the best known side effects of using opium is spasm of the
      sphincter of Oddi, which may increase the diameter of the extrahepatic bile
      ducts. Ultrasound is the first imaging modality used for evaluating the biliary
      system because it is commonly available and noninvasive. The principal objective
      of this study was to measure the common bile duct (CBD) diameter via
      ultrasonography in opium addicts and to evaluate the relation between the CBD
      diameter and the period of addiction. MATERIALS AND METHODS: This research was an
      analytical-cross sectional study that was done on 110 opium addicts that were
      admitted to a drug treatment center. The diameter of the CBD in these cases was
      measured by ultrasonography and the results were analyzed with other factors like
      age, the period of addiction and the laboratory findings. RESULTS: According to
      the findings, there is a significant increase in the range of the CBD diameter in
      comparison with normal bile ducts. Also, the mean diameter of the CBD in the
      different age groups showed a significant difference (p < 0.0001) and there was a
      significant relation between the CBD diameter and the period of addiction (p <
      0.001, r = 0.74); so, with the increased length of the addiction period, the mean
      CBD diameter increases. CONCLUSION: Opium addiction is one of the factors that
      causes extrahepatic bile duct dilatation, so in these cases, if no obstructing
      lesion was found on ultrasound examination and the serum bilirobine and alkaline
      phosphatase levels are normal, then further evaluation is not needed.

PMID- 17554189
TI  - FDG-PET for evaluating the antitumor effect of intraarterial 3-bromopyruvate
      administration in a rabbit VX2 liver tumor model.
AB  - OBJECTIVE: We wanted to investigate the feasibility of using FDG-PET for
      evaluating the antitumor effect of intraarterial administration of a hexokinase
      II inhibitor, 3-bromopyruvate (3-BrPA), in a rabbit VX2 liver tumor model.
      MATERIALS AND METHODS: VX2 carcinoma was grown in the livers of ten rabbits. Two
      weeks later, liver CT was performed to confirm appropriate tumor growth for the
      experiment. After tumor volume-matched grouping of the rabbits, transcatheter
      intraarterial administration of 3-BrPA was performed (1 mM and 5 mM in five
      animals each, respectively). FDG-PET scan was performed the day before,
      immediately after and a week after 3-BrPA administration. FDG uptake was
      semiquantified by measuring the standardized uptake value (SUV). A week after
      treatment, the experimental animals were sacrificed and the necrosis rates of the
      tumors were calculated based on the histopathology. RESULTS: The SUV of the VX2
      tumors before treatment (3.87+/-1.51 [mean+/-SD]) was significantly higher than
      that of nontumorous liver parenchyma (1.72+/-0.34) (p < 0.0001, Mann-Whitney U
      test). The SUV was significantly decreased immediately after 3-BrPA
      administration (2.05+/-1.21) (p = 0.002, Wilcoxon signed rank test). On the one
      week follow up PET scan, the FDG uptake remained significantly lower (SUV 1.41+/
      0.73) than that before treatment (p = 0.002), although three out of ten animals
      showed a slightly increasing tendency for the FDG uptake. The tumor necrosis rate
      ranged from 50.00% to 99.90% (85.48%+/-15.87). There was no significant
      correlation between the SUV or the SUV decrease rate and the tumor necrosis rate
      in that range. CONCLUSION: Even though FDG-PET cannot exactly reflect the tumor
      necrosis rate, FDG-PET is a useful modality for the early assessment of the
      antitumor effect of intraarterial administration of 3-BrPA in VX2 liver tumor.

PMID- 17554190
TI  - A new technique for superselective catheterization of arteries: preshaping of a
      micro-guide wire into a shepherd's hook form.
AB  - OBJECTIVE: We wanted to introduce a new technique for superselective
      catheterization of arteries with preshaping of a micro-guide wire into a
      shepherd's hook form, and this is useful for superselection of small arteries
      branching at an acute angle from a large parent artery for the treatment of
      tumors and hemorrhages. MATERIALS AND METHODS: We developed a superselective
      catheterization technique by using preshaping of a micro-guide wire into a
      shepherd's hook form. We encountered six patients in our practice for whom we
      failed to catheterize the small tumor-feeding arteries that branched at an acute
      angle from wide parent arteries during chemoembolization of hepatocellular
      carcinoma; the parent arteries were the right inferior phrenic artery (n = 4) and
      the left gastric artery (n = 1) from the celiac axis with celiac stenosis due to
      compression by the median arcuate ligament and the proper hepatic artery from the
      gastroduodenal artery (n = 1) in a patient who had celiac axis occlusion with
      collateral circulation via the pancreaticoduodenal arcade from the superior
      mesenteric artery. In these consecutive six patients, we tested the usefulness of
      this new technique with employing preshaping of a micro-guide wire into a
      shepherd's hook form for superselective catheterization of targeted vessels.
      RESULTS: The target arteries were successfully catheterized and satisfactory
      transcatheter arterial chemoembolization was performed in all six patients. There
      were no significant complications such as arterial dissection. CONCLUSION: We
      developed a technique that is effective for superselection of vessels with
      preshaping of micro-guide wire into a shepherd's hook form, and we successfully
      applied it during chemoembolization of hepatocellular carcinoma. This technique
      can be useful for superselection of small arteries that branch from a large
      parent artery at acute angles for the treatment of tumors and hemorrhages.

PMID- 17554191
TI  - Prospective analysis on the relation between pain and prostate volume during
      transrectal prostate biopsy.
AB  - OBJECTIVE: We wanted to assess the relationship between pain and the prostate
      volume during transrectal ultrasound (TRUS) guided biopsy. MATERIALS AND METHODS:
      Between July and September 2006, 71 patients scheduled for TRUS biopsy of the
      prostate were considered for inclusion to this study. These patients underwent
      periprostatic neurovascular bundle block with lidocaine prior to biopsy. Pain was
      assessed using a Visual Analogue Scale (VAS) during periprostatic neurovascular
      bundle block (VAS 1), during biopsy (VAS 2), and 20 minutes after biopsy (VAS 3).
      The mean pain scores were analyzed in the large prostate group (prostate volume >
      40 cc) and the small prostate group (prostate volume< or =40 cc). P values < 0.05
      were considered significant. RESULTS: The mean prostate volume was 42.2 cc
      (standard deviation: 8.6). The mean pain scores of VAS 1, 2 and 3 were 4.70+/
      1.61, 3.15+/-2.44 and 1.05+/-1.51, respectively. In the large prostate group, the
      mean pains scores of VAS 1, 2 and 3 were 4.75+/-1.76, 3.51+/-2.76 and 1.29+/
      1.70, respectively, whereas in the small prostate group, the means pain scores
      were 4.66+/-1.46, 2.77+/-2.0, and 0.80+/-1.26, respectively. Although there were
      no statistical differences of VAS 1, the larger prostate group revealed higher
      pain scores of VAS 2 and 3 compared with the small prostate group (p < 0.05).
      CONCLUSION: Patients with larger prostate volumes tend to feel more pain during
      and after TRUS guided prostate biopsy. Our findings suggest that additional
      analgesic strategies may be necessary when the patients with larger prostate
      undergo TRUS guided prostate biopsy.

PMID- 17554193
TI  - Traumatic neuroma around the celiac trunk after gastrectomy mimicking a nodal
      metastasis: a case report.
AB  - Traumatic neuroma is a well-known disorder that occurs after trauma or surgery
      involving the peripheral nerve and develops from a nonneoplastic proliferation of
      the proximal end of a severed, partially transected, or injured nerve. We present
      a case of traumatic neuroma around the celiac trunk after gastrectomy in a 56
      year-old man, which was confirmed by pathology. CT demonstrated the presence of a
      lobulated, homogeneous, hypoattenuating mass around the celiac trunk, mimicking a
      nodal metastasis.

PMID- 17554192
TI  - Anterior cruciate ligament tear: reliability of MR imaging to predict stability
      after conservative treatment.
AB  - OBJECTIVE: The aim of this study is to evaluate the reliability of MR imaging to
      predict the stability of the torn anterior cruciate ligament (ACL) after complete
      recovery of the ligament's continuity. MATERIALS AND METHODS: Twenty patients
      with 20 knee injuries (13 males and 7 females; age range, 20-54) were enrolled in
      the study. The inclusion criteria were a positive history of acute trauma,
      diagnosis of the ACL tear by both the physical examination and the MR imaging at
      the initial presentation, conservative treatment, complete recovery of the
      continuity of the ligament on the follow up (FU) MR images and availability of
      the KT-2000 measurements. Two radiologists, who worked in consensus, graded the
      MR findings with using a 3-point system for the signal intensity, sharpness,
      straightness and the thickness of the healed ligament. The insufficiency of ACL
      was categorized into three groups according to the KT-2000 measurements. The
      statistic correlations between the grades of the MR findings and the degrees of
      ACL insufficiency were analyzed using the Cochran-Mantel-Haenszel test (p <
      0.05). RESULTS: The p-values for each category of the MR findings according to
      the different groups of the KT-2000 measurements were 0.9180 for the MR signal
      intensity, 1.0000 for sharpness, 0.5038 for straightness and 0.2950 for thickness
      of the ACL. The MR findings were not significantly different between the
      different KT-2000 groups. CONCLUSION: MR imaging itself is not a reliable
      examination to predict stability of the ACL rupture outcome, even when the MR
      images show an intact appearance of the ACL.

PMID- 17554194
TI  - Extramedullary plasmacytoma involving the bilateral adrenal glands on MR imaging.
AB  - We report here on a 64-year-old woman with extramedullary plasmacytoma involving
      the bilateral adrenal glands. Primary adrenal extramedullary plasmacytoma is
      extremely rare and only three cases of extramedullary plasmacytoma in the
      unilateral adrenal gland have currently been reported on. This case is of
      interest in that the bilateral adrenals were involved. In this article, we
      present the MRI findings and we briefly review the relevant literature.

PMID- 17554195
TI  - Stroke from delayed embolization of polymerized glue following percutaneous
      direct injection of a carotid body tumor.
AB  - A 52-year-old male with right carotid body tumor underwent direct percutaneous
      glue (n-butylcyanoacrylate [NBCA]) embolization. Several hours later, he
      developed left hemiparesis from embolization of the polymerized glue cast.
      Migration of glue during percutaneous tumor embolization is presumed to occur
      only in the liquid state, which may lead to stroke or cranial nerve deficits. To
      the best of our knowledge, this is the first report of delayed glue embolization
      from a treated hypervascular tumor of the head and neck.

PMID- 17554196
TI  - Breast cancer from the excisional scar of a benign mass.
AB  - Breast cancer developing from a surgical scar is rare; this type of malignancy
      has been reported in only 12 cases to date. Herein, we report on a 52-year-old
      female who developed infiltrating ductal carcinoma in a surgical scar following
      excision of a benign mass. Two years previously, the patient underwent surgery
      and radiotherapy for invasive ductal carcinoma of the contralateral breast. The
      initial appearance of the scar was similar to fat necrosis; it was observed to be
      progressively shrinking on follow-up sonography. On the two year follow-up
      ultrasound, the appearance changed, an angular margin and vascularity at the
      periphery of the scar were noted. A biopsy and subsequent excision of the scar
      were performed; the diagnosis of infiltrating ductal carcinoma of the scar was
      confirmed.

PMID- 17554197
TI  - Primary mucinous adenocarcinoma of a seminal vesicle cyst associated with ectopic
      ureter and ipsilateral renal agenesis: a case report.
AB  - Primary adenocarcinoma of the seminal vesicles is a rare neoplasm. Congenital
      seminal vesicle cysts are commonly associated with unilateral renal agenesis or
      dysgenesis. To the best of our knowledge, mucinous adenocarcinoma of the seminal
      vesicle cyst that's associated with an ectopic ureter opening into the seminal
      vesicle and ipsilateral renal agenesis has not been described in the radiological
      literature. We report here on the radiological findings of a primary
      adenocarcinoma of a seminal vesicle cyst in this condition.

PMID- 17554198
TI  - Notice of redundant publication. Does the oropharyngeal fat tissue influence the
      oropharyngeal airway in snorers? Dynamic CT study.

PMID- 17554199
TI  - Differential regulation of microRNAs by p53 revealed by massively parallel
      sequencing: miR-34a is a p53 target that induces apoptosis and G1-arrest.
AB  - In a genome-wide screen for microRNAs regulated by the transcription factor
      encoded by the p53 tumor suppressor gene we found that after p53-activation the
      abundance of thirty-four miRNAs was significantly increased, whereas sixteen
      miRNAs were suppressed. The induction of miR-34a was most pronounced among all
      differential regulations. Also expression of the primary miR-34a transcript was
      induced after p53 activation and by DNA damage in a p53-dependent manner. p53
      occupied an evolutionarily conserved binding site proximal to the first non
      coding exon of miR-34a. Ectopic miR-34a induced apoptosis and a cell cycle arrest
      in the G1-phase, thereby suppressing tumor cell proliferation. Other p53-induced
      miRNAs identified here may also have tumor suppressive potential as they are
      known to suppress the anti-apoptotic factor Bcl2 (miR-15a/16) and the oncogenes
      RAS and HMGA2 (let-7a). Our results for the first time directly integrate the
      regulation of miRNA expression into the transcriptional network regulated by p53.
      siRNAs corresponding to p53-induced miRNAs may have potential as cancer
      therapeutic agents as RNA interference based therapies are currently emerging.

PMID- 17554200
TI  - Diet and vitamin or mineral supplementation and risk of colon cancer by subsite
      in Canada.
AB  - The study assesses the association of diet and vitamin or mineral supplementation
      with risk of proximal or distal colon cancer. Mailed questionnaires were
      completed by 1723 newly diagnosed, histologically confirmed colon cancer cases
      and 3097 population controls between 1994 and 1997 in seven Canadian provinces.
      Measurement included information on socio-economic status, physical activity,
      smoking habits, alcohol use, diet and vitamin or mineral supplementation. Odds
      ratios and 95% confidence intervals were derived through unconditional logistic
      regression. Linear regression was used to examine that dietary factors affect
      body mass index. The strongest positive associations between colon cancer risk
      and increasing total fat intake were observed for proximal colon cancer in men
      and for distal colon cancer in both men and women. Increased consumption of
      vegetables, fruit and whole-grain products did not reduce the risk of colon
      cancer. A modest reduction in distal colon cancer risk was noted in women who
      consumed yellow-orange vegetables. Significant positive associations were
      observed between proximal colon cancer risk in men and consumption of red meat
      and dairy products, and between distal colon cancer risk in women and total
      intake of meat and processed meat. We also saw strong associations between bacon
      intake and both subsites of colon cancer in women. When men were compared with
      women directly by subsite however, the results did not show a corresponding
      association. A significantly reduced risk of distal colon cancer was noted in
      women only with increasing intake of dairy products and of milk. Among men and
      women taking vitamin and mineral supplements for more than 5 years, significant
      inverse associations with colon cancer were most pronounced among women with
      distal colon cancer. These findings suggest that dietary risk factors for
      proximal colon cancer may differ from those for distal colon cancer.

PMID- 17554201
TI  - Colonoscopy surveillance in asymptomatic subjects with increased risk for
      colorectal cancer: clinical evaluation and cost analysis of an Italian
      experience.
AB  - The aim of this study was three-fold: (a) to present a surveillance plan for
      colorectal cancer prevention with colonoscopy, focused on first-degree relatives
      of colorectal cancer patients in the province of Ferrara (Italy); (b) to analyse
      the cost of colonoscopy at the University Hospital of Ferrara; and (c) to analyse
      the cost of the surveillance plan in our province. In January 2000, in the
      province of Ferrara, following a campaign of public sensitization, a plan of
      surveillance with colonoscopy was started, addressing the population at an
      increased risk for colorectal cancer (i.e. over 45-year-old first-degree
      relatives of patients with either colorectal cancer or adenomatous polyps
      revealed before 60 years of age). In addition, we estimated the cost of
      colonoscopy both at the University Hospital of Ferrara and of the surveillance
      plan. Between January 2000 and October 2003, 585 individuals at increased risk
      were interviewed. Five hundred and forty-four (94%) accepted to undergo a
      colonoscopy. By October 2003, 439 (81%) colonoscopies had been performed.
      Colonoscopy was normal in 330 individuals (75%). In 109 individuals (25%), 144
      lesions were found: 35 patients (32%) had hyperplastic polyps, 66 (61%) had
      adenomas, and eight (7%) adenocarcinomas (six Dukes A, one Dukes B, and one Dukes
      C stage). Out of a total of 101 adenomas, 68 were tubular adenomas (67%), 24
      tubulo-villous adenomas (24%), and nine adenomas with high-grade dysplasia (9%).
      The cost of colonoscopy at our hospital and the costs of the surveillance plan
      amounted to euro 130.84 (euro 169.57 with single biopsy) and euro 43,103.66 (euro
      42 310.34/year), respectively. These data show (a) the efficacy of colonoscopy in
      the early diagnosis of colorectal cancer and premalignant lesions in first-degree
      relatives of colorectal cancer patients; (b) the low cost of colonoscopy at the
      centre performing the surveillance; and (c) the feasibility of screening and
      surveillance programmes for colorectal cancer prevention.

PMID- 17554202
TI  - Tomato lycopene extract supplementation decreases insulin-like growth factor-I
      levels in colon cancer patients.
AB  - Epidemiological studies have shown that high serum levels of insulin-like growth
      factor-I are associated with an increased risk of colon and other types of
      cancer. The aim of this study was to determine whether short intervention with
      dietary tomato lycopene extract will affect serum levels of the insulin-like
      growth factor system components in colon cancer patients. The study had a double
      blind, randomized, placebo-controlled design. Colon cancer patients (n=56),
      candidates for colectomy, were recruited from the local community a few days to a
      few weeks before surgery. Personal and medical data were recorded. Plasma
      concentrations of insulin-like growth factor-I and II and insulin-like growth
      factor-I-binding protein-3 were assayed by routine laboratory methods. Lycopene
      was assayed by high-performance liquid chromatography. Plasma lycopene levels
      increased by twofold after supplementation with tomato lycopene extract. In the
      placebo-treated group, there was a small nonsignificant increase in lycopene
      plasma levels. The plasma concentration of insulin-like growth factor-I decreased
      significantly by about 25% after tomato lycopene extract supplementation as
      compared with the placebo-treated group (P<0.05). No significant change was
      observed in insulin-like growth factor-I-binding protein-3 or insulin-like growth
      factor-II, whereas the insulin-like growth factor-I/insulin-like growth factor-I
      binding protein-3 molar ratio decreased significantly (P<0.05). Given that high
      plasma levels of insulin-like growth factor-I have been suggested as a risk
      factor for various types of cancer including colon cancer, the results support
      our suggestion that tomato lycopene extract has a role in the prevention of colon
      and possibly other types of cancer.

PMID- 17554203
TI  - Cancerogenic effect of different fragments of the hepatitis C virus core protein.
AB  - The hepatitis C virus core protein plays an extremely important role in the
      hepatocarcinogenesis of hepatitis C virus. Little, however, is known about the
      oncogenic potency of fragments. Thus, the purpose of the present study is to
      investigate the cancerogenic effects of the different core protein fragments. Two
      series of recombinant plasmids containing hepatitis C virus core gene fragments
      encoding the different-length core protein were constructed using plasmid
      enhanced green fluorescent protein (pEGFP)-C1 and pcDNA3.1(+), respectively.
      Human hepatocyte L02 cells transiently transfected with pEGFP-C1-based plasmids
      were subjected to confocal laser scanning microscopy analysis to determine the
      localization of the different core protein fragments. The stably transfected L02
      cells with the pcDNA3.1(+)-based core protein plasmids were used to investigate
      the ultrastructural effects of the core protein and the tumorigenicity of L02
      cells expressing core protein fragments in athymic nude mice. The full-length
      core protein and Core130-191 were completely localized in the cytoplasm, while
      Core1-59 existed exclusively in the nucleus. On the other hand, Core50-140 and
      Core1-140 were observed in both the nucleus and the cytoplasm. Ultrastructural
      changes of L02 cells expressing the full-length core protein were comprehensive
      and included, for example, irregular nuclear, increased nuclear/cytoplasmic ratio
      and mitochondria swelling. The slight changes were observed in the cells
      expressing Core50-140 and Core130-191, whereas the ultrastructure of the cells
      expressing Core1-59 remained normal. All the L02 cells stably expressing
      different fragments of the core protein, with the exception of the C-terminal
      truncated fragment Core1-59, could induce the occurrence of tumor in the nude
      mice. The N-terminal fragment of the core protein, Core1-59, was not oncogenic,
      while the intermediate and posterior segments of the hepatitis C virus core
      protein had the cancerogenic potency. In view of the existence of many important
      immunogenic epitopes in it, the core protein anterior segment might be a safer
      candidate for the development of hepatitis C virus vaccine.

PMID- 17554204
TI  - Fruit and vegetable consumption and gastric cancer by location and histological
      type: case-control and meta-analysis.
AB  - The available information favours a greater impact of environmental exposures on
      intestinal type gastric cancer, and risk factors for the cardia and distal
      stomach cancers also appear to be different. We aimed to estimate the association
      between fruit and vegetable intake and gastric cancer, by location and
      histological type. We performed a population-based case-control study and a meta
      analysis of studies addressing this issue. Incident cases (n=305) were identified
      in two large teaching hospitals (Porto, Portugal), and controls were randomly
      sampled among city dwellers (n=1129). Published studies were searched through
      PubMed, and effects were combined with random effects meta-analysis. In our case
      control study, the odds ratio (OR) for the comparison of the highest vs. lowest
      tertile of fruit consumption was 0.47 [95% confidence interval (CI): 0.21-1.05]
      for cardia, 0.53 (95% CI: 0.35-0.80) for non-cardia cancer, 0.36 (95% CI: 0.20
      0.62) for intestinal, and 1.00 (95% CI: 0.53-1.90) for the diffuse histological
      type. For vegetables, the corresponding OR was 0.59 (95% CI: 0.26-1.35), 0.85
      (95% CI: 0.58-1.26), 0.95 (95% CI: 0.57-1.57), and 0.60 (95% CI: 0.32-1.14). In
      meta-analysis, considering fruit consumption (highest vs. lowest category), the
      combined OR was 0.58 (95% CI: 0.38-0.89) for cardia, 0.61 (95% CI: 0.44-0.84) for
      non-cardia, 0.49 (95% CI: 0.33-0.72) for intestinal type, and 0.82 (95% CI: 0.57
      1.20) for diffuse type. Vegetables also decreased the risk of cardia (OR=0.63,
      95% CI: 0.50-0.79), non-cardia (OR=0.75, 95% CI: 0.59-0.95), intestinal (OR=0.61,
      95% CI: 0.44-0.86), and diffuse type (OR=0.67, 95% CI: 0.44-1.01). Fruit or
      vegetable intake was associated with a decreased risk of gastric cancer
      regardless of the anatomical location and the histological type, although dietary
      intake had a more clear-cut protective effect on intestinal type cancers.

PMID- 17554205
TI  - Prostate cancer mortality predictions for Ireland up to 2015.
AB  - The objective of this analysis was to predict average world age-standardized
      mortality rates per person-years (100,000 person-years) and numbers of prostate
      cancer deaths in Ireland for the years 2005, 2010 and 2015. Poisson linear and
      log-linear regression models of Irish prostate cancer mortality data for the
      years 1950-2002 were used to predict trends for the whole population, for men
      aged 0-64 and 50-74 years. The prostate cancer world age-standardized mortality
      rate in 2015 is predicted to remain unchanged from the average recorded in 1998
      2002, while, because of population growth, the number of deaths is predicted to
      increase. In persons under 65 years of age, the world age-standardized mortality
      rate is expected to increase, but the number of deaths in this age group is
      expected to nearly double between 2002 and 2015. Similarly, the world age
      standardized mortality rate for men aged 50-74 years is predicted to rise with
      the number of deaths in this age group expected to increase sharply. The
      historical evidence predicts a small increase of age-adjusted prostate cancer
      mortality rates in Ireland and only in the age groups of 0-64 and 50-74 years in
      the next 10 years, along with a continuing marked increase in number of deaths
      due to demographic change.

PMID- 17554206
TI  - Resveratrol-induced growth inhibition in MDA-MB-231 breast cancer cells is
      associated with mitogen-activated protein kinase signaling and protein
      translation.
AB  - Resveratrol (3,4',5-trans-trihydroxystilbene) is a natural compound found in
      grapes and several medicinal plants and has been shown to have anticancer effects
      on various human cancer cells. The aim of this study was to further investigate
      the molecular mechanism of this anticancer effect. Resveratrol effect on cell
      growth, morphology and gene expression was investigated in estrogen receptor
      negative MDA-MB-231 human breast cancer cell line. We show here that resveratrol
      induced growth inhibition in the estrogen receptor negative MDA-MB-231 breast
      cancer cells is due to the induction of apoptosis as demonstrated by
      morphological, nuclear staining and PARP cleavage analysis. Resveratrol-induced
      growth inhibition was associated with transient activation of p44/42 mitogen
      activated protein kinase (MAPK) (Thr202/Tyr204). Most importantly, resveratrol
      inhibited both the phosphorylation at Ser240/244 and the expression of the pS6
      ribosomal protein. This protein is known to play an important role in the
      translation of mRNAs that have oligopyrimidine tracts in their 5' untranslated
      regions. Interestingly, only MAPK inhibitor was able to block resveratrol-induced
      growth inhibition suggesting that effects of resveratrol on cell growth are
      dependent on MAPK signaling. The data demonstrated that resveratrol-induced
      apoptosis is associated with MAPK signaling and with the inhibition of proteins
      that are involved in protein translation. This is the first data linking
      resveratrol with downregulation of protein translation via p44/42 MAPK and S6
      ribosomal protein. We propose to use these proteins as predictive biomarkers to
      evaluate the treatment efficacy of resveratrol in estrogen receptor-negative
      human breast cancer.

PMID- 17554207
TI  - Induction of apoptosis in MCF-7 and MDA-MB-231 breast cancer cells by Oligonol is
      mediated by Bcl-2 family regulation and MEK/ERK signaling.
AB  - Oligonol is a novel catechin-rich biotechnology product. The role of oligonol in
      modulating intracellular signaling mechanisms was investigated with the view of
      demonstrating its potential chemopreventive effect and the ability to inhibit
      cell proliferation using the estrogen-responsive MCF-7 and the estrogen
      unresponsive MDA-MB-231 human breast cancer cell lines. Cell survival assay
      indicated that Oligonol was cytotoxic to both cells. Oligonol triggered apoptosis
      as revealed by the morphological features typical of nucleus staining and the
      accumulation of sub-G1 peak. Treatment with 25 microg/ml Oligonol resulted in an
      activation of caspase-7 and up-regulation of Bad on MCF-7 cells, while the
      Oligonol (20 microg/ml) induced up-regulation of Bcl-2 protein in a time-response
      manner on MDA-MB-231 cells. ERK1/2 in both cells were inactivated after Oligonol
      treatment in a time-dependent manner, and also inactivated upstream MEK1/2.
      Oligonol triggers apoptosis in MCF-7 and MDA-MB-231 cells through the modulation
      of pro-apoptotic Bcl-2 family proteins and MEK/ERK signaling pathway.

PMID- 17554208
TI  - Head and neck cancer: a case for inhibition by isothiocyanates and indoles from
      cruciferous vegetables.
AB  - Chemical carcinogens derived from cigarettes and other tobacco products, as well
      as betel quid, paan, and alcohol consumption, are commonly associated with head
      and neck cancer risk. This is a particularly debilitating cancer, with a high
      recurrence rate and long-term treatment comorbidities affecting health and
      lifestyle. Controlling tobacco access or use may be an ideal prevention strategy
      but may also be challenging or undesired. Individuals, however, may be able to
      reduce their risk through simple and focused dietary change. Results from
      epidemiologic studies, basic research, and clinical investigations suggest that a
      diet rich in cruciferous vegetables may increase carcinogen metabolism, induce
      apoptosis, and reduce the risk of developing a primary head and neck tumor. This
      review briefly summarizes head and neck cancer nutritional epidemiology, and then
      describes the biochemical and epidemiologic literature describing the effects of
      crucifer consumption on head and neck carcinogenesis. To translate these
      findings, the strengths and limitations of specific intervention models are
      discussed, including differences in target populations and the choice of a food
      based or pill-based approach for intervention. Addressing these factors in a
      future intervention may define a low-cost and non-toxic approach to reduce the
      burden of head and neck cancer.

PMID- 17554209
TI  - Prevention of melatonin suppression by nocturnal lighting: relevance to cancer.
AB  - The decreased melatonin production in humans and animals caused by environmental
      lighting, especially short wavelength lighting (between 470 and 525 nm) has been
      shown to be associated with an increased risk of cancer. The purpose of this
      study was to investigate whether blocking light in this wavelength range under
      bright light may prevent the suppression of melatonin, which could help to
      prevent cancer. Optical filter lenses were designed, allowing selective exclusion
      of all wavelengths below 530 nm. Salivary melatonin levels were measured under
      dim light (<5 lux), bright light (800 lux) and filtered light (800 lux) at hourly
      intervals between 2000 and 0800 h in 11 healthy young male participants (mean age
      23.5+/-1.5 years). The measurements were taken during three nonconsecutive nights
      over a 2-week period. The Dim Light Melatonin Onset test was used as a marker of
      circadian phase. Nine of the 11 participants demonstrated preserved melatonin
      levels in filtered light similar to their dim light secretion profile. With
      filtered light, the participants had a mean relative amount of melatonin of 91.2
      (P>0.05 between dim light and experimental condition). Unfiltered bright light
      drastically suppressed melatonin production with a mean relative amount of
      melatonin of 25.4 (P<0.05 between dim light and experimental condition).
      Preventing melatonin deficiencies using lenses that block light of low wavelength
      from reaching the retina presents a cost-effective, practical solution to the
      problem of increased malignancy rates in shift workers.

PMID- 17554210
TI  - Changes in the antioxidant defense and hepatic drug metabolizing enzyme and
      isoenzyme levels, 8-hydroxydeoxyguanosine formation and expressions of c-raf.1
      and insulin-like growth factor II genes during the stages of development of
      hepatocellular carcinoma in rats.
AB  - This is an extensive study in a defined initiation-promotion hepatocellular
      carcinoma model of hepatocarcinogenesis (in rats) in which many important marker
      enzymes and isoenzymes and 8-hydroxydeoxyguanosine formation have been studied
      together with two very important cellular proliferating genes, insulin-like
      growth factor II and c-raf.1, known for their role in hepatocellular cancer
      development. Experiments were carried out on hepatic tissues of male Sprague
      Dawley rats. Variations in different enzyme/isoenzyme
      activities/contents/expression pattern and 8-hydroxydeoxyguanosine-positive cells
      were studied. Insulin-like growth factor II and c-raf.1 gene expressions were
      monitored. A direct shift with increase in size and numbers of lesions was found
      to occur in different experimental groups. In this study, glutathione peroxidase
      (1.14 and 1.46-fold) and reduced triphosphopyridine nucleotide (TPNH)-cytochrome
      c-reductase (1.94 and 2.94-fold) activities, cytochrome b5 (1.57 and 3.28-fold)
      and P-450 contents (1.45 and 1.22-fold), glutathione content (1.27 and 1.45-fold)
      and superoxide dismutase and catalase (1.16 and 1.39-fold) activities in group A
      animals were found to be lower than those in initiation and promotion studies,
      respectively. 8-Hydroxydeoxyguanosine-positive nuclei count showed that oxidative
      damage of nuclear DNA enhanced with the progress of the disease. The insulin-like
      growth factor II expression was found to be predominant in hepatocellular
      carcinoma and in early preneoplastic lesions. Unlike insulin-like growth factor
      II, c-raf.1 expression was located in the late basophilic lesions associated with
      hepatocellular carcinoma. During the various stages of the development of
      hepatocellular carcinoma, the enzymes played a significant role in metabolizing
      carcinogens and thereby scavenging various toxic metabolites or free radicals
      produced. A sequence of cellular changes starting from the appearance of glycogen
      storage foci to basophilic foci leading to hepatocellular carcinoma via mixed
      cell foci varied the activity/content or expression pattern of the enzymes and
      isoenzymes and in 8-hydroxydeoxyguanosine formation. It has been established that
      c-raf.1-induced signaling pathways activated by insulin-like growth factor II is
      implicated in the late stage of development of cancer.

PMID- 17554211
TI  - Social disparities in breast and cervical cancer preventive practices.
AB  - Knowledge of factors related to the use of preventive practices is essential in
      order to build strategies to decrease cancer incidence and mortality. The aim of
      this study is to describe the characteristics of women who periodically use
      cervical smear and mammography. This is a cross-sectional study based on the 2001
      Balearic Health Survey, using a stratified sample of non-institutionalized
      population resident in the Balearic Islands. The study included 560 women, aged
      20 years or over. The variables studied were age, marital status, social class,
      education, place of residence and birth, self-perceived health status,
      satisfaction with health services, job status and type of medical coverage. A
      multivariate analysis was performed using logistic regression models. Thirty-five
      per cent had regular mammography (72% between 50 and 64 years) and 54% had
      cervical smears. The probability of having undergone mammography is higher in
      women between the ages of 50 and 64 years [odds ratio (OR)=11.74; interval
      confidence (IC): 5.89-23.39] and in those with additional medical coverage
      (OR=1.97; IC: 1.19-3.27) and much lower in single women (OR=0.22; IC: 0.10-0.49).
      The probability of having undergone a Pap test increases according to educational
      level (OR=2.25; IC: 0.98-5.18 for women in the higher level) and social class
      (OR=1.98; IC: 0.91-4.28 for social class I) and decreases in women older than 65
      years (OR=0.15; IC: 0.07-0.35) and in single women (OR=0.29; IC: 0.16-0.50). Age
      and marital status are factors related to both practices. Socio-economic status
      remains associated with cervical smear use, while having an additional medical
      coverage increases the probability of regular mammography.

PMID- 17554212
TI  - Increasing the price of tobacco: economically regressive today and probably
      ineffective tomorrow.
AB  - The tobacco price increase during the fourth stage of the smoking epidemic has
      coincided with a decrease in smoking prevalence, less marked in the lower socio
      economic groups. In countries that are at the third stage of the epidemic,
      smoking prevalence in poor and less educated women has not changed or has
      increased at the same time as tobacco prices have increased. It is assumed,
      however, that people with low incomes and those with less education in developed
      countries are more responsive to price changes. The inconsistent results with
      regard to the price elasticity of tobacco in different socio-economic groups and
      the conflicting trends in smoking prevalence between socio-economic groups during
      periods of increased tobacco prices do not support that consensus. Evidence
      suggests that increasing tobacco taxation is a regressive measure today and will
      probably achieve only a moderate reduction in tobacco use in the future, as
      smoking is becoming a phenomenon associated with poorer and less-educated people.

PMID- 17554213
TI  - User acceptability and feasibility of self-testing with HIV rapid tests.
AB  - OBJECTIVE: Because HIV rapid tests are considered for self-testing, this study
      aims to determine the user acceptability and feasibility of self-testing.
      METHODS: A cross-sectional study was performed on 350 systematically sampled
      participants across 2 Singapore HIV testing centers using the Abbott Determine
      HIV 1/2 blood sample rapid test (Abbott Laboratories, Abbott Park, IL).
      Participants were surveyed on knowledge of and attitudes toward rapid testing. To
      determine interrater agreement between self-testing and trained personnel
      testing, participants performed self-testing with visual instructions, followed
      by trained personnel testing. Ability to identify test outcomes was determined
      through interpretation of sample test results. RESULTS: Eighty-nine percent of
      participants preferred testing in private, but most indicated that confidential
      counseling by trained counselors was necessary. Almost 90% found the kit easy to
      use and instructions easy to understand. Nevertheless, 85% failed to perform all
      steps correctly, especially blood sampling, and 56% had invalid results because
      of incorrect test performance. Interrater agreement between results from self
      testing and trained personnel testing had a kappa value of 0.28. Twelve percent
      could not correctly determine results using sample tests, including 2% and 7% who
      read positive and negative samples, respectively, incorrectly. CONCLUSIONS: A
      substantial proportion could not perform self-testing or identify outcomes. Self
      testing with the Determine HIV 1/2 kit in Singapore should be deferred.

PMID- 17554214
TI  - Condom use rather than serosorting explains differences in HIV incidence among
      men who have sex with men.
AB  - BACKGROUND: HIV incidence is high and increasing among men who have sex with men
      (MSM) attending the Sexually Transmitted Infection (STI) Outpatient Clinic in
      Amsterdam but remains low among MSM in the Amsterdam Cohort Studies (ACS). We
      studied whether sexual behaviors in these 2 groups are consistent with
      serosorting and if serosorting explains the difference in HIV incidence. METHODS:
      In 2004 to 2006, a survey of sexual behaviors and HIV status regarding up to 4
      traceable partners in the prior 6 months was performed in MSM attending the STI
      Outpatient Clinic (high-risk) and in MSM in the ACS (lower risk). Moreover,
      pooled information was collected on anonymous partners. We used logistic
      regression to test whether sexual behaviors are consistent with serosorting and
      to test whether risk group is associated with having concordant traceable
      partners among men reporting unprotected anal intercourse (UAI). RESULTS: We
      included 513 MSM (54% lower risk and 75% HIV-negative). Lower risk and high-risk
      MSM with concordant traceable partners were more likely to have UAI than MSM with
      discordant partners or partners of unknown HIV status (P < 0.001). Risk group was
      not associated with having concordant UAI. Compared with lower risk MSM, however,
      high-risk MSM frequently had UAI with nonconcordant traceable partners and with
      anonymous partners. CONCLUSIONS: Sexual risk behaviors with traceable partners
      are consistent with serosorting. Nonetheless, the higher level of UAI with
      anonymous or nonconcordant traceable partners more likely explains the increasing
      HIV incidence seen among STI Outpatient Clinic attendees than a difference in
      serosorting behavior.

PMID- 17554215
TI  - Analytic insights into the population level impact of imperfect prophylactic HIV
      vaccines.
AB  - The population level implications of imperfect HIV vaccines were studied using a
      mathematical model. A criterion for determining the utility of a vaccine at the
      population level is introduced, and 2 useful summary measures, namely, vaccine
      utility (phi) and vaccine infection fitness (psi), are derived and shown to
      characterize the population-level utility once vaccine efficacies are determined.
      The utility of the vaccine alone does not guarantee a substantial impact,
      however, because the effectiveness of partially effective vaccines also depends
      on the prevailing level of HIV infectious spread. Therefore, a second criterion
      is introduced through a third summary measure, the hazard index (xi), to describe
      the effectiveness of a vaccine in substantially reducing HIV incidence. The
      qualitative features of the impact are delineated by studying 4 distinct
      scenarios of HIV vaccination. Accordingly, our work delineates the link between
      vaccine efficacies and the impact of vaccination at the population level and
      provides the tools for vaccine developers to assess the utility and effectiveness
      of a given imperfect vaccine straightforwardly and rapidly.

PMID- 17554216
TI  - Association of HIV-1 replication capacity with treatment outcomes in patients
      with virologic treatment failure.
AB  - BACKGROUND: The extent to which HIV-1 replication capacity (RC) influences the
      response to therapy remains to be established. METHODS: Phenotypic susceptibility
      and RC of baseline isolates (n = 139) from patients enrolled in the ARGENTA trial
      were measured and correlated to treatment outcomes over 36 months. RESULTS: RC in
      baseline isolates correlated with the number of phenotypically active drugs (R =
      0.34, P < 0.001). Crude viral RC did not predict treatment outcomes. When viral
      RC was adjusted by baseline CD4 cell counts, HIV-1 RNA levels, and phenotypic
      susceptibility to the rescue regimen, it showed significant association with the
      immunologic outcome (per log10 RC higher, mean difference in 36 months' time
      averaged change from baseline CD4 count = -68 cells/microL; P = 0.020). In the
      subgroup of patients with 3 or more phenotypically active drugs in the salvage
      regimen (n = 35, median RC = 65%), subjects carrying isolates with RC < or =65%
      as compared to those with RC >65% had better time-averaged HIV-1 RNA responses
      (mean: -1.04 vs. -0.32 log10 copies/mL; P = 0.012) and CD4 cell responses (mean:
      132 vs. -7 cells/microL; P = 0.006). Among patients with HIV-1 RNA levels
      persistently >500 copies/mL (n = 61), RC, on a log10 basis, was inversely
      associated with time-averaged 36-month CD4 cell responses (beta = -0.26; P =
      0.046). CONCLUSION: After normalizing for viral susceptibility to the employed
      regimen or in patient subsets with suboptimal virologic response, higher viral RC
      may predict worse subsequent treatment outcomes.

PMID- 17554217
TI  - Long-term efficacy and safety of tipranavir boosted with ritonavir in HIV-1
      infected patients failing multiple protease inhibitor regimens: 80-week data from
      a phase 2 study.
AB  - BACKGROUND: BI 1182.2, an open-label, randomized, multicenter, phase 2 study,
      evaluated efficacy and tolerability of the protease inhibitor (PI) tipranavir
      (TPV; 500 mg twice daily or 1000 mg twice daily) administered with ritonavir (100
      mg twice daily) in combination with 1 nucleoside reverse transcriptase inhibitor
      and 1 nonnucleoside reverse transcriptase inhibitor in multiple PI-experienced
      HIV-1-infected patients. METHODS: Forty-one patients were evaluated in 2 arms:
      low-dose (19 patients) or high-dose (22 patients) ritonavir-boosted tipranavir
      (TPV/r). Primary endpoints were change from baseline in HIV-1 RNA concentrations
      at weeks 16, 24, 48, and 80 and percentage of patients with plasma HIV-1 RNA
      levels lower than the limit of quantitation. Safety was evaluated by adverse
      events (AEs), grade 3/4 abnormalities, and serious AEs. RESULTS: Of all patients,
      59% were still receiving TPV/r (14 in low-dose arm and 10 in high-dose arm) at
      week 80. Patients in both arms had a median >2.0-log10 reduction in plasma viral
      load. Intent-to-treat analysis demonstrated that a similar proportion of patients
      in the high-dose and low-dose groups achieved plasma HIV-1 RNA levels <50
      copies/mL at week 80 (43% vs. 32%; P = 0.527). The most frequently observed AEs
      were diarrhea, headache, and nausea. CONCLUSION: TPV/r combined with other active
      antiretroviral agents can provide a durable treatment response for highly
      treatment-experienced patients.

PMID- 17554218
TI  - Kitesurfing: when fun turns to trauma-the dangers of a new extreme sport.

PMID- 17554219
TI  - Large chronic epidural hematoma with calcification: a case report.

PMID- 17554220
TI  - Pseudoaneurysm of the external carotid artery after a blunt facial trauma.

PMID- 17554221
TI  - Neo-ossification of the cricothyroid joint after elective cricothyroidotomy: a
      case report and discussion on the merits of this procedure.

PMID- 17554222
TI  - Traumatic complete hemipelvectomy treated with a free fillet flap.

PMID- 17554223
TI  - Attempted suicide by auto-injection of polyurethane (PU) foam: report of a case.

PMID- 17554224
TI  - Survival of an elderly patient with blunt traumatic cardiac rupture.

PMID- 17554226
TI  - "It's my hormones, doctor"--does physical activity help with menopausal symptoms?
AB  - OBJECTIVE: Many women experience health problems when going through menopause,
      and these health problems may result in a substantial reduction in quality of
      life. There are some indications that physical activity may play a role in
      ameliorating menopausal symptoms, but there is conflicting evidence about this.
      To assess the relationship between changes in physical activity and self-reported
      vasomotor, somatic, and psychological symptoms. DESIGN: Data from the third
      (2001) and fourth (2004) surveys of the Australian Longitudinal Study on Women's
      Health were used. Data from 3,330 middle-aged women were included in the
      analyses. In linear regression models, the relationships between changes in
      physical activity of at least moderate intensity and total menopausal, vasomotor,
      somatic, and psychological symptoms were determined. RESULTS: Physical activity
      was not associated with total menopausal symptoms, vasomotor or psychological
      symptoms. A weak association with somatic symptoms (B = -0.003; 95% CI: -0.005 to
      -0.001) was found. Weight gain was associated with increased total, vasomotor,
      and somatic symptoms. Weight loss was associated with a reduction in total and
      vasomotor symptoms. CONCLUSION: Changes in physical activity were not related to
      vasomotor or psychological symptoms and only marginally to somatic symptoms.
      Changes in weight showed a stronger relationship with menopausal symptoms. The
      relationship between weight change and menopausal symptoms merits further
      exploration.

PMID- 17554227
TI  - Evaluation of facial function with a questionnaire: reliability and validity.
AB  - OBJECTIVES: To analyze the validity and reliability of assigning House-Brackmann
      facial nerve grade based on a patient-administered questionnaire. Specifically,
      the use of a questionnaire was studied for evaluation of the long-term facial
      function after microsurgical resection of vestibular schwannoma (VS). STUDY
      DESIGN: Three neurotologists with more than 25 years of experience and 3
      neurotology clinical fellows rated facial nerve grade in a blinded fashion based
      on the questionnaire. The standard to which the questionnaires were compared was
      the facial nerve grade assigned to the patient during an office visit near the
      same time as the completed patient questionnaire. METHODS: Thirty-four patients
      had an office evaluation of facial function at least 1 year after microsurgical
      resection of a VS. Thirty patients had a sporadic VS, whereas 4 patients had
      neurofibromatosis 2. The average tumor size was 2.2 cm. A postoperative
      questionnaire regarding facial function was completed within 2 months of the
      office evaluation. Statistical analyses were performed to compare the office
      evaluation rating with the questionnaire rating (validity) and to analyze
      interobserver reliability. RESULTS: The association between the facial nerve
      grade assigned by the office evaluation and the questionnaire was highly
      significant (p<0.01), with a mean correlation (Spearman [rho]) equal to 0.94. The
      interobserver reliability was high, with coefficients ranging from 0.93 to 0.99
      (p<0.01; mean=0.97). Because a large proportion of patients had normal (House
      Brackmann Grade I) facial function, an additional analysis was performed with
      these patients excluded. The high levels of interobserver reliability persisted
      (average=0.96). CONCLUSION: When compared with office evaluation, a patient
      administered questionnaire provides a valid and reliable measure of long-term
      facial function after VS surgery.

PMID- 17554228
TI  - Vestibular schwannoma volume as a predictor of hearing outcome after surgery.
AB  - OBJECTIVES: To validate the prognostic capacity of several preoperative and
      intraoperative parameters of hearing preservation after vestibular schwannoma
      surgery. STUDY DESIGN: A retrospective study of a consecutive series of 29
      patients treated with the enlarged middle cranial fossa approach. Quantitative
      parameters were tumor volume, linear tumor size, pure-tone and speech audiometry,
      pure-tone average, speech discrimination score, speech reception threshold,
      auditory brainstem response (ABR; intra-aural interpeak latency I-V, interaural
      wave V latency difference), and the vestibular caloric test (speed and
      frequency). Qualitative parameters were fundus involvement by the tumor (in
      magnetic resonance imaging and surgical record), nerve of tumor origin (in
      magnetic resonance imaging and surgical record), ABR parameters (well-shaped
      ABRs: waves I, III, and V present; presence of wave V). METHODS: All patients
      were divided into 2 groups on the basis of postoperative hearing: preserved
      hearing (55%) or nonpreserved hearing (45%). The Kolmogorov-Smirnov test was used
      to evaluate normality of distribution for continuous data. The t test was applied
      for normally distributed continuous data and the Mann-Whitney test for
      nonnormally distributed continuous data. The chi2 test was used for comparisons
      of categoric data. RESULTS: Tumor volume was found to be the only statistically
      significant prognostic parameter for hearing preservation (p = 0.007). The cutoff
      point for the "critical" tumor volume for hearing preservation was calculated to
      0.20 cm. None of the other parameters reached statistical significance.
      CONCLUSION: Tumor size is a predictive factor for hearing preservation after
      vestibular schwannoma surgery, and patients with smaller tumors, based on volume
      measurement, have significantly better chances for retaining hearing. This has an
      impact on decision making and timing of surgery.

PMID- 17554229
TI  - Biocompatibility of polylactides in the middle ear: an experimental animal study.
AB  - OBJECTIVE: To study the suitability of resorbable polylactides for reconstruction
      in middle ear surgery. EXPERIMENTAL ANIMALS: Twenty-four chinchillas.
      INTERVENTIONS: Twenty chinchillas were operated on using 2 types of polylactides
      inserted into the middle ear and outer ear canal, 10 animals in each group. At 6
      months, the animals were killed, and their temporal bones were removed for
      sectioning. Degree of inflammation, fibrosis, degradation of polylactide
      material, and new bone formation were assessed histologically. MAIN OUTCOME
      MEASURES: Polylactide implants caused only a mild local inflammation, with no
      difference between the 2 materials tested. CONCLUSION: Polylactide acid-based
      middle ear implants were successfully used in the reconstructive middle ear
      surgery. Resorption occurred without complications.

PMID- 17554230
TI  - Audiometric outcomes of tympanoplasty with hydroxylapatite prosthesis: consultant
      versus trainees.
AB  - OBJECTIVE: To assess and compare the audiometric outcomes and surgical
      complication rates of tympanoplasty with hydroxylapatite (HA) prostheses
      performed by a single consultant and advanced trainees. STUDY DESIGN: A
      retrospective case review was undertaken. SETTING: Tertiary referral center.
      PATIENTS: One hundred eighteen cases of primary and revision tympanoplasty were
      included in the study performed during a 6-year period. INTERVENTION:
      Tympanoplasty with HA prosthesis. MAIN OUTCOME MEASURES: Preoperative and
      postoperative audiometric data were compared for both the consultant and trainee
      groups. Details of the surgical procedure and operative complications were also
      recorded. RESULTS: Fifty-eight procedures were performed by the consultant and 60
      operations were performed by trainees. The average improvement in air-bone gap
      (ABG) for consultants was 14.8 dB, with a 95% confidence interval (10.4, 19.2)
      (paired t test; test statistic: t=6.80, 57 df, p<0.01), whereas for trainees, the
      average improvement in ABG was 7.8 dB, with a 95% confidence interval (4.1, 11.6)
      (paired t test; test statistic: t=4.19, 59 df, p<0.01). The difference of 7.0 dB
      in mean ABG between the 2 groups was significant (two-sample t test; test
      statistic: t=2.44, 116 df, p=0.02). There was no significant difference in the
      surgical procedure or in the number of revision operations performed by the
      consultant or trainees. Surgical complication rates were comparable for the two
      groups. CONCLUSION: In this series, the consultant achieved a significantly
      better closure in ABG than trainees for tympanoplasty with HA prostheses.

PMID- 17554232
TI  - [Niacin in therapy].
AB  - Niacin (nicotinic acid and nicotinamide) is a vitamin used as a source of the
      NAD+ and NADP+ coenzymes required for many metabolic processes. Its low dietary
      levels induce the development of pellagra. Niacin has been used for decades in
      the treatment of patients with disturbed lipid and lipoprotein metabolism, this
      being the main cause of atherosclerotic changes in cardiovascular diseases. It is
      still the most efficacious drug in terms of its ability to increase HDL
      cholesterol content accompanied by a decrease in all atherogenic lipoproteins
      (VLDL, LDL, and L(a)) as well as fatty acids and triglycerides. Niacin also
      increases adiponectin level, which might result in additional atheroprotection.
      There are studies confirming the beneficial action of niacin against migraine and
      hyperphosphatemia associated with renal failure, ethanol-induced
      neurodegeneration, and loss of beta-cell function in type 1 diabetes. Moreover,
      it augments plasma tryptophan concentrations in HIV-infected patients and thyroid
      radiosensitivity to 131I. Inhibition of the invasion of hepatoma cells has also
      been proven. However, it is necessary to point out that the currently applied
      niacin preparations might exhibit such side effects as cutaneous flushing,
      gastrointestinal disturbances, and hepatotoxicity, particularly during treatment
      with sustained-release niacin preparations. The recent discovery of the G-protein
      coupled receptor GPR109A, which mediates the antilipolytic effects induced by
      nicotinic acid in adipocytes as well as cutaneous vasodilation, allows the
      development of new agents interacting with this receptor. In view of these
      observations, niacin therapy must be accompanied by control of the choice of
      niacin preparation and its dose in order to eliminate or at least limit its side
      effects.

PMID- 17554233
TI  - [The characteristics of focal adhesion kinase (FAK) and its role in
      carcinogenesis].
AB  - Focal adhesion kinase (FAK) is a 125-kDa cytoplasmic tyrosine kinase located in
      cells which create attachments with the extracellular matrix (ECM) or with other
      cells. The primary function of FAK is to transmit the signal coming from the
      integrine receptor, participating in adhesion, to the intracellular protein
      cascade. The FAK kinase transducing the signal indirectly plays a crucial role in
      many cellular processes. This protein is engaged in cell cycle regulation,
      adhesion, migration, invasion and metastasis, cytoskeleton protein
      phosphorylation, and apoptosis. Deregulation of the FAK-dependent processes, e.g.
      adhesion, growth, viability, and cell mobility, is a significant element of
      cancer progression. FAK protein level expression is varies widely and depends on
      the development grade of the cancer. A minor FAK overexpression is already
      observed in the preinvasion grade, increasing significantly in the invasive
      state. The high FAK expression correlates with cancer cell migration, invasion,
      and ability for metastasis. The evaluation of FAK expression in cancer cells
      might become an important prognostic factor, since FAK expression studies provide
      important information that provides the opportunity to identify the cancer grade.

PMID- 17554234
TI  - [Molecular markers of micrometastasis in the blood of hepatocellular carcinoma
      patients].
AB  - The frequent occurrence of metastases from the primary tumor present a major
      therapeutic problem in hepatocellular cancer because of the hematogenous spread
      of cancer cells. Standard imaging diagnostics methods do not allow for an early
      detection of relapse of the disease, as opposed to the analysis of molecular cell
      markers, especially mRNA-based methods, in peripheral blood samples by RT-PCR.
      Analysis of alphafetoprotein expression is the "gold standard" in the diagnostics
      of HCC at the protein and mRNA level because of its specificity for liver cancer.
      However, working out an analysis protocol is problematic and the utility of the
      marker in monitoring a patient's status in the perioperative period remains
      controversial. New HCC markers are being searched for among the highly liver
      specific ones and those shared between various cancers types. Markers associated
      with freely circulating nucleic acids are also studied and quantitative assays
      are used. An assay for several markers simultaneously could give satisfactory
      results.

PMID- 17554235
TI  - [Bevacizumab: progress in the treatment of metastatic cancer and hope for
      patients with proliferative retinopathy].
AB  - The formation of new blood vessels from pre-existing vasculature
      (neoangiogenesis) accompanies many diseases, including cancer and proliferative
      retinopathy. Knowledge of the molecular mechanisms of angiogenesis and
      angiogeneic factors, especially vascular endothelial growth factor (VEGF),
      enables the design of drugs more potent and specific in their action and less
      cytotoxic. Among angiogenesis inhibitors are drugs made by means of genetic
      engineering, i.e. monoclonal antibodies, devoid of unwanted actions that occur
      during chemotherapy. One of monoclonal antibodies successfully used in clinical
      trials in patients with metastatic colorectal cancer is bevacizumab. Because of
      its inhibitory potential regarding angiogenesis it may be useful in the treatment
      of age-related macular degeneration (AMD). Although anti-VEGF agents have already
      been used in AMD therapy, there are several arguments, primarily financial,
      favoring bevacizumab's applicability in ophthalmology.

PMID- 17554236
TI  - [Humoral-circulatory response in the somato-vegetative reflex caused by pain
      factors].
AB  - The somato-vegetative reflex is an organism's answer to physical stress,
      resulting from the action of miscellaneous stimuli on extero- and
      proprioreceptors. It is realized in two types of responses of alarm groups:
      Response to a stressor with superiority of the parasympathetic system. This is
      not often present and manifests as decrease in pulse, heart stroke volume and
      pressure. An adrenergic response to a stressor, realized sequntionally in time
      periods. The neurogenic phase and humoral phase connected with the ejection of
      amine from the core of the suprarenal gland are separately distingiushed in this
      type of response. Significant increase in blood pressure, vascular resistance,
      augmentation of flow of blood in the aorta and tachycardia were observed in these
      two phases to a considerable extent. An important role in this reflex is
      performed by the limbic system, whose activation causes a circulation of
      stimulation in the Papez emotive district, which lies at the basis of the
      appearance of vegetative symptoms of emotions. Knowledge of the mechanism of this
      reflex is important, as it may play an important role, without the participation
      of the consciousness (anesthesia) in diagnosing pain in miscellaneous surgical
      and dental procedures and sharp pain syndromes, as well as the prevention of the
      occurrence of this reflex and its hemodynamic repercussion.

PMID- 17554237
TI  - [Ultrasound--mechanisms of action and application in sonodynamic therapy].
AB  - Ultrasound is a mechanical wave at a frequency beyond human hearing. In nature,
      ultrasound waves of low frequency are emitted and received by many animal
      species. However, people are interested in ultrasound which is artificially
      produced because of its possible practical applications. The wide spectrum of
      ultrasound (US) application in industrial technology and devices of general use
      poses a risk to human health because ultrasound in high doses can be harmful.
      People can also be exposed to ultrasound generated during medical treatment,
      mainly in ultrasound diagnostics and therapy as well as surgery. The possible
      risk to human health creates the need for investigation of the effects and
      mechanisms of its biological activity. The mechanisms of ultrasound action on
      biological material can be divided into thermal and nonthermal. Thermal effects
      occur when acoustic energy is absorbed and transformed to heat and depends on the
      absorption and dissipation of ultrasound energy. Nonthermal mechanisms can be
      classified as cavitational and shear stress. Shear stress includes the effects of
      the radiation pressure, radiation force, and acoustic streaming. Cavitation
      leading to the formation of reactive oxygen species and its consequences are of
      primary interest. To support photodynamic cancer therapy in the 1970s, the idea
      of sonodynamic cancer therapy was formulated. Sonodynamic therapy is a promising
      new technique for killing cancer cells based on the synergistic interactions of
      ultrasound and certain chemical compounds called "sonosensitizers". In spite of
      the experimental proof of the existence of the sonodynamic effect, attempts of a
      clear qualification of the mechanism of this process have been unsuccessful.

PMID- 17554238
TI  - [Current status of research on conjugates and related drug delivery systems in
      the treatment of cancer and other diseases].
AB  - Drug delivery systems is an umbrella term describing different types of carrier
      drug and carrier-protein conjugates, liposomes, polyplexes, micelles, and hybrid
      types. Such systems were designed with the aim to enhance delivery and to improve
      the selectivity and pharmacological properties of both conventional drugs and
      newly developed agents. In this review the current state-of-the-art in the design
      of drug delivery systems is described, with particular emphasis on agents
      developed to deliver antitumor agents. The advantages, limitations, and
      disadvantages of the particular types of drug delivery systems as well as the
      theoretical and practical basis of their action are also highlighted here. In
      addition, results of preclinical and clinical studies on the most developed
      examples of drug delivery systems to date are summarized.

PMID- 17554239
TI  - The Provenge decision.

PMID- 17554242
TI  - Effect of atorvastatin on energy expenditure and skeletal muscle oxidative
      metabolism at rest and during exercise.
AB  - Statins are associated with adverse effects in skeletal muscle. This study tested
      the hypothesis that atorvastatin would increase the respiratory exchange ratio
      (RER) at rest and during exercise. Twenty-eight healthy subjects (mean age 52
      years) were enrolled in a double-blind, placebo-controlled, randomized study of
      the effects of atorvastatin (40 mg/day) on whole body energetics over 8 weeks.
      Ventilatory gas exchange measurements, at rest and during bicycle ergometry, were
      used to assess muscle oxidative metabolism. Thirteen subjects from each treatment
      arm completed the study. Eight weeks of atorvastatin lowered plasma low-density
      lipoprotein cholesterol concentration but had no effect on resting or submaximal
      energy expenditure, RER, or calculated fatty acid oxidation rates. Atorvastatin
      did not affect maximal exercise oxygen consumption or the anaerobic threshold.
      Eight weeks of atorvastatin therapy was not associated with alterations in
      substrate oxidation, or muscle oxidative function at rest, or during exercise in
      healthy adults.

PMID- 17554243
TI  - Developments in post-marketing comparative effectiveness research.
AB  - Physicians and insurers need to weigh the effectiveness of new drugs against
      existing therapeutics in routine care to make decisions about treatment and
      formularies. Because Food and Drug Administration (FDA) approval of most new
      drugs requires demonstrating efficacy and safety against placebo, there is
      limited interest by manufacturers in conducting such head-to-head trials.
      Comparative effectiveness research seeks to provide head-to-head comparisons of
      treatment outcomes in routine care. Health-care utilization databases record drug
      use and selected health outcomes for large populations in a timely way and
      reflect routine care, and therefore may be the preferred data source for
      comparative effectiveness research. Confounding caused by selective prescribing
      based on indication, severity, and prognosis threatens the validity of non
      randomized database studies that often have limited details on clinical
      information. Several recent developments may bring the field closer to acceptable
      validity, including approaches that exploit the concepts of proxy variables using
      high-dimensional propensity scores, within-patient variation of drug exposure
      using crossover designs, and between-provider variation in prescribing preference
      using instrumental variable (IV) analyses.

PMID- 17554244
TI  - Influence of CYP3A5 genotype on the pharmacokinetics and pharmacodynamics of the
      cytochrome P4503A probes alfentanil and midazolam.
AB  - The hepatic and first-pass cytochrome P4503A (CYP3A) probe alfentanil (ALF) is
      also metabolized in vitro by CYP3A5. Human hepatic microsomal ALF metabolism is
      higher in livers with at least one CYP3A5*1 allele and higher CYP3A5 protein
      content, compared with CYP3A5*3 homozygotes with little CYP3A5. The influence of
      CYP3A5 genotype on ALF pharmacokinetics and pharmacodynamics was studied, and
      compared to midazolam (MDZ), another CYP3A probe. Healthy volunteers (58 men, 41
      women) were genotyped for CYP3A5 *1, *3, *6, and *7 alleles. They received
      intravenous MDZ then ALF, and oral MDZ and ALF the next day. Plasma MDZ and ALF
      concentrations were determined by mass spectrometry. Dark-adapted pupil diameters
      were determined coincident with blood sampling. In CYP3A5(*)3/(*)3 (n=62),
      (*)1/(*)3 (n=28), and (*)1/(*)1 (n=8) genotypes, systemic clearances of ALF were
      4.6+/-1.8, 4.8+/-1.7, and 3.9+/-1.7 ml/kg/min and those of MDZ were 7.8+/-2.3,
      7.7+/-2.3, and 6.0+/-1.4 ml/kg/min, respectively (not significant), and apparent
      oral clearances were 11.8+/-7.2, 13.3+/-6.1, and 12.6+/-8.2 ml/kg/min for ALF and
      35.2+/-19.0, 36.4+/-15.7, and 29.4+/-9.3 ml/kg/min for MDZ (not significant).
      Clearances were not different between African Americans (n=25) and Whites (n=68),
      or between CYP3A5 genotypes within African Americans. ALF pharmacodynamics was
      not different between CYP3A5 genotypes. There was consistent concordance between
      ALF and MDZ, in clearances and extraction ratios. Thus, in a relatively large
      cohort of healthy subjects with constitutive CYP3A activity, CYP3A5 genotype had
      no effect on the systemic or apparent oral clearances, or pharmacodynamics, of
      the CYP3A probes ALF and MDZ, despite affecting their hepatic microsomal
      metabolism.

PMID- 17554245
TI  - The importance of harmonizing food composition data across Europe.
AB  - OBJECTIVE: To examine the role of food composition data in Europe in four
      sectors, namely health, trade regulation and legislation, agriculture and the
      environment. RESULTS: The need for further harmonization of data across Europe is
      clearly identified and evidenced from a number of previous successful European
      collaborations. CONCLUSIONS: Data on the nutritional composition of foods are
      essential for a broad spectrum of activities, including public health nutrition,
      research, the food industry and government policy development and implementation.
      With the expansion of the European Union and the concomitant increase in cross
      border trade and cooperation harmonizing food composition data becomes a more
      important issue than ever. Harmonization is not solely a technical issue, but
      also involves creating durable and sustainable structures to maintain the
      viability of the data. These are some of the issues currently being addressed by
      the European Food Information Resource Network of Excellence.

PMID- 17554246
TI  - Effect of moderate alcohol consumption on adipokines and insulin sensitivity in
      lean and overweight men: a diet intervention study.
AB  - OBJECTIVE: Moderate alcohol consumption is associated with a decreased risk of
      type II diabetes. This study investigates the effect of moderate alcohol
      consumption on adipokines and insulin sensitivity. SUBJECTS: Twenty healthy, lean
      (body mass index (BMI) 18.5-25 kg/m(2); n=11) or overweight (BMI>27 kg/m(2); n=9)
      men (18-25 years). METHODS: Three cans of beer (40 g alcohol) or alcohol-free
      beer daily during 3 weeks. RESULTS: Adiponectin and ghrelin concentrations
      increased (P<0.01) by 11 and 8%, while acylation-stimulating protein (ASP)
      concentrations decreased by 12% (P=0.04) after moderate alcohol consumption.
      Concentrations of leptin and resistin remained unchanged. Insulin sensitivity by
      an oral glucose tolerance test (OGTT) was not affected by moderate alcohol
      consumption, but 2 h glucose concentrations were lower (P=0.01) after beer (4.5+/
      0.1 mmol/l) than alcohol-free beer (4.9+/-0.1 mmol/l). Both free fatty acids and
      glucagon concentrations showed a stronger increase (P<0.01) after 90 min during
      OGTT after beer than alcohol-free beer. Changes of adiponectin were positively
      correlated (r=0.69, P<0.001), and changes of leptin (r=-0.53, P=0.016) and ASP
      (r=-0.43, P=0.067) were negatively correlated with changes of insulin sensitivity
      index. All these results did not differ between lean and overweight men.
      CONCLUSIONS: Moderate alcohol consumption increased adiponectin and ghrelin,
      while it decreased ASP concentrations both in lean and overweight men. These
      changes are in line with the hypothesized improvement of insulin sensitivity, but
      did not affect insulin sensitivity within 3 weeks of moderate alcohol
      consumption.

PMID- 17554247
TI  - Five-year follow-up of a cognitive-behavioural lifestyle multidisciplinary
      programme for childhood obesity outpatient treatment.
AB  - OBJECTIVE: Aim of this study is to examine the 5-year follow-up results of MI
      PIACE PIACERMI (I like to like and please myself), a cognitive-behavioural
      programme intended to obtain a weight growth regulation over an extended period.
      DESIGN: Longitudinal observational clinical study. SETTING: Hospital-based
      programme, through outpatient activities. SUBJECTS: Thirty-one simple obese
      children, 13 boys and 18 girls, 6-12 years of age on admission. INTERVENTION: The
      intervention was carried out by a multidisciplinary team (paediatrician,
      cognitive-behavioural psychologist, physical therapist). It employed cognitive
      behavioural techniques, nutrition education, promotion of physical activity,
      setting a high value on free play in motion. The programme actively involves
      parents. The following measurements were taken on admission and at 5-year follow
      up: height, weight, waist circumference, body mass index (BMI), BMI standardized
      (BMI-SDS), and adjusted BMI (a-BMI) as actual BMI/BMI (50th percentile)*100.
      Dietary habits were investigated by interview and 24-h recall. Parents completed
      the Family Habit Inventory and the Child Behaviour Checklist (CBCL). Motor skills
      were assessed by using Frostig's test. RESULTS: The dropout rate was 35.5%. In
      subjects who completed the 5-year follow-up, the mean and s.d. of BMI-SDS and a
      BMI were, respectively, 4.23+/-0.71 and 54.7%+/-9.0 at baseline and 2.74+/-0.85
      and 43.2%+/-17.3 at the last visit. Waist circumference decreased. Family habits
      improved significantly. Total energy intake was significantly reduced. Emotional
      and social aspects of obesity-related behaviours showed positive changes. Motor
      skills globally improved. CONCLUSIONS: The study provides further evidence that
      positive persistent results may be obtained in obese children with treatment
      programmes combining a lifestyle centred approach, parental involvement,
      nutrition education and cognitive-behavioural strategies.

PMID- 17554248
TI  - Randomized controlled trial for an effect of green tea-extract powder
      supplementation on glucose abnormalities.
AB  - OBJECTIVE: We examined whether green tea-extract powder supplementation improves
      glucose abnormality. METHODS: The study was conducted for volunteers who resided
      in eastern communities of Shizuoka Prefecture and who had fasting blood glucose
      levels of >or=6.1 mmol/l or nonfasting blood glucose levels of >or=7.8 mmol/l in
      a recent health check-up. Sixty subjects aged 32-73 years (49 males and 11
      females) participated in the trial. The Early intervention group consumed a
      packet of green tea-extract powder containing 544 mg polyphenols (456 mg
      catechins) daily for the first 2 months and then entered the 2-month
      nonintervention period. The Later intervention group was observed for the first 2
      months and then consumed green tea-extract powder as described above for the
      subsequent 2 months. Using the two-period crossover design, we analyzed the
      changes in fasting hemoglobin A1c level and other biomarkers in blood samples
      collected at baseline, 2 months and 4 months. RESULTS: A significant reduction in
      hemoglobin A1c level and a borderline significant reduction in diastolic blood
      pressure were associated with the intervention. The intervention caused no
      significant changes in weight, body mass index, body fat, systolic blood
      pressure, fasting serum glucose level, homeostasis model assessment index, serum
      lipid level or hypersensitive C-reactive protein. CONCLUSION: Daily supplementary
      intake of green tea-extract powder lowered the hemoglobin A1c level in
      individuals with borderline diabetes.

PMID- 17554249
TI  - Zinc supplementation in the management of shigellosis in malnourished children in
      Bangladesh.
AB  - OBJECTIVE: To assess the impact of zinc supplementation on clinical recovery,
      weight gain and subsequent growth and morbidity in moderately malnourished
      children with shigellosis. DESIGN: A randomized, double-blind, controlled trial.
      SETTING: Dhaka hospital of ICDDR,B: Centre for Health and Population Research,
      Dhaka, Bangladesh. SUBJECTS: Fifty-six moderately malnourished children, aged 12
      59 months with culture-proven shigellosis. METHODS: Subjects were randomly
      allocated to receive zinc (20 mg/day elemental) in multivitamin syrup
      (intervention) or multivitamin syrup without zinc (control) in two equally
      divided doses daily for 2 weeks. All children received pivmecillinam in a dose of
      15 mg/kg every 6 h for 5 days. After supplementation, children were followed in
      their respective homes every 2 weeks for 6 months. RESULTS: Children receiving
      zinc recovered from acute illness significantly faster than the control children
      (P<0.05). The medians time (days) to recovery and disappearances of blood and
      mucous were significantly 50% shorter in the zinc-supplemented group compared to
      the control group. The mean body weight of zinc supplemented children increased
      significantly from 8.8 kg on admission to 9.2 kg (P<0.01) at recovery, which was
      not observed in the control children (from 9.3 to 9.6 kg; P=0.12). During the 6
      month follow-up period, zinc-supplemented children had significantly fewer mean
      episodes of diarrhoea compared to the control children (2.2 vs 3.3; P=0.03).
      CONCLUSION: Zinc supplementation significantly shortens the duration of acute
      shigellosis, promotes better weight gain during recovery and reduces diarrhoeal
      morbidity during the subsequent 6 months.

PMID- 17554250
TI  - Nutrition Screening Tool for Every Preschooler (NutriSTEP): validation and test
      retest reliability of a parent-administered questionnaire assessing nutrition
      risk of preschoolers.
AB  - OBJECTIVES: Study 1: To establish the validity of scores on Nutrition Screening
      Tool for Every Preschooler (NutriSTEP), a community-based parent-administered
      screening tool for assessing nutrition risk, by comparing scores to an expert
      rating. Study 2: To demonstrate test-retest reliability of NutriSTEP.
      SUBJECTS/METHODS: Study 1: Parents of 269 preschoolers (of 294 parents recruited
      from the community), completed the NutriSTEP questionnaire; a registered
      dietitian (RD) assessed the nutritional status (based on medical and nutritional
      history, 3 days of dietary recall and anthropometric measurements) of these
      preschoolers and rated their nutritional risk (1 (low) to 10 (high risk)).
      Receiver operating characteristic (ROC) curves were used to establish validity
      and determine appropriate cut points based on sensitivity and specificity. Study
      2: Parents of 140 preschoolers (of 161 recruited) completed NutriSTEP on two
      occasions. Intraclass correlation (ICC) and kappa were used to assess
      reliability. RESULTS: Study 1: Scores on NutriSTEP and the RD rating were
      correlated (r=0.48, P=0.01). Area under the ROC curve for the high risk RD rating
      (score 8+) and the moderate risk rating (score 5+) were 81.5 and 73.8%,
      respectively. A moderate risk cut point of >20 and high risk cut point of >25
      were identified for the NutriSTEP scores. Study 2: The NutriSTEP score was
      reliable between administrations (ICC=0.89, F=16.7, P<0.001). Most items on the
      questionnaire had adequate (kappa>0.5) or excellent (kappa>0.75) agreement.
      CONCLUSIONS: The NutriSTEP questionnaire is both valid and reliable for
      determining nutritional risk in preschoolers.

PMID- 17554251
TI  - Measurement of hemodialysis vascular access flow using extracorporeal temperature
      gradients.
AB  - A reduction in vascular access flow poses a risk for thrombosis. We present a new
      technique to measure vascular access flow during dialysis based on extracorporeal
      temperature gradients, and their changes, on reversing the extracorporeal
      bloodlines without having to inject an indicator. Fistula temperatures were
      measured by the blood temperature monitor with normal line position and after
      manual switching of the bloodlines using the same extracorporeal blood flow. The
      access flow by our temperature gradient method (TGM) was compared to access flow
      derived by saline dilution with measurements in the same patients repeated in
      subsequent weeks. In 70 pairs of TGM and saline dilution measurements in 35
      patients, the repeatability of the TGM measurements was not significantly
      different from that of saline dilution. There was a highly significant
      correlation between the two techniques with an acceptable confidence level for
      limits of agreement for the difference between them. It took about 9 min to
      complete the TGM method and about 5 min for saline dilution. Our studies show
      that the novel TGM method showed excellent agreement and reproducibility with the
      saline dilution method without the need for indicator dilution.

PMID- 17554252
TI  - Bone growth during daily or intermittent calcitriol treatment during renal
      failure with advanced secondary hyperparathyroidism.
AB  - Calcitriol is a standard therapy for secondary hyperparathyroidism in chronic
      renal failure. We evaluated whether the effect of daily or intermittent
      calcitriol administration is more efficient in enhancing bone growth in renal
      failure with advanced secondary hyperparathyroidism in weanling 5/6
      nephrectomized rats loaded with phosphorus to induce severe secondary
      hyperparathyroidism. The animals were treated daily or three times weekly with
      calcitriol for 4 weeks but the total weekly dose of calcitriol was the same.
      Although calcitriol increased the serum calcium, it did not lower parathyroid
      hormone (PTH) or improve tibia and body length. Animals with renal failure and
      advanced secondary hyperparathyroidism had decreased PTH/PTHrP, which was
      accompanied by an increase in the cyclin kinase inhibitor p57(Kip2). Calcitriol
      treatment upregulated the PTH/PTHrP receptor but also increased inhibitors of
      cell proliferation such as p21(Waf1/Cip1), IGFBP3, and FGFR3. Calcitriol also
      enhanced markers of chondrocyte differentiation, such as IGF1, Vitamin D
      receptor, FGF23, and bone morphogenetic protein-7. Receptor activator of nuclear
      factor-kappabeta ligand levels improved with calcitriol treatment but without
      changes in osteoprotegerin suggesting an enhancement of
      osteo/chondroclastogenesis and mineralization. Overall, both daily and
      intermittent calcitriol had similar effects on endochondral bone growth in
      phosphorus-loaded rats with renal failure.

PMID- 17554253
TI  - Patient and allograft survival of Indo Asian and East Asian dialysis patients
      treated in Canada.
AB  - Kidney failure is relatively common among Canadians of Asian origin. However,
      little is known about the health outcomes after initiation of renal replacement
      therapy in this population. Our study evaluates differences in the likelihood of
      renal transplantation and graft loss among Asian and white patients. We studied
      21 523 adults of East Asian, Indo Asian or white ethnicity who had initiated
      dialysis in Canada from 1990-2000. Subjects were followed until death, loss to
      follow-up or end of study (2004). The proportion of the eligible subjects who
      were East Asian, Indo Asian, or white was 6, 3, and 91%, respectively. Compared
      to white patients, East Asian and Indo Asian patients were significantly less
      likely to receive a renal transplant after adjusting for potential confounding
      factors. This disparity is greater for transplants from living donors as compared
      to those from deceased donors. The adjusted death censored graft loss in
      transplant recipients was not significantly different between ethnic groups. The
      adjusted risk of death following transplantation, however, was significantly
      lower in Indo Asian than in white patients. Our findings show that in a Canadian
      population, patients of East Asian or Indo Asian origin had lower rates of renal
      transplantation than white patients, especially for living donor transplantation.
      These findings warrant further study, especially given the good graft outcomes in
      these individuals.

PMID- 17554254
TI  - Collagen alpha5 and alpha2(IV) chain coexpression: analysis of skin biopsies of
      Alport patients.
AB  - Alport syndrome is a collagen type IV disease caused by mutations in the COL4A5
      gene with the X-linked form being most prevalent. The resultant alpha5(IV)
      collagen chain is a component of the glomerular and skin basement membranes
      (SBMs). Immunofluorescent determination of the alpha5(IV) chain in skin biopsies
      is the procedure of choice to identify patients. In 30% of patients, however, the
      mutant protein is still found in the SBM resulting in a normal staining pattern.
      In order to minimize or eliminate false results, we compared the distribution of
      the alpha2(IV) chain (another SBM component) and the alpha5(IV) chain by standard
      double label immunofluorescence (IF) and by confocal laser scanning microscopy.
      The study was performed on 55 skin biopsies of patients suspected of Alports and
      five normal control specimens. In normal skin, IF showed the classical linear
      pattern for both collagens along the basement membrane. Additionally, decreased
      alpha5(IV) was found in the bottom of the dermal papillary basement membrane.
      Confocal analysis confirmed the results and show alpha5(IV) focal interruptions.
      In suspected patients, both techniques showed the same rate of abnormal
      alpha5(IV) expression: segmental in women and absent in men. Our results show a
      physiological variation of alpha5(IV) location with focal interruptions and
      decreased expression in the bottom of the dermal basement membrane. Comparison of
      alpha5(IV) with alpha2(IV) expression is simple and eliminates technical
      artifacts.

PMID- 17554255
TI  - Albumin and whole-body protein synthesis respond differently to intraperitoneal
      and oral amino acids.
AB  - Patients with peritoneal dialysis are at risk for malnutrition and
      hypoalbuminemia, which are indicators of poor outcome. Recently, it was shown
      that dialysis solutions containing amino acids (AAs) and glucose improve protein
      anabolism in peritoneal dialysis patients. We determined if the same solutions
      could increase the fractional synthesis rate of albumin along with whole-body
      protein synthesis. Changes in the fractional albumin synthetic rate reflect acute
      change in hepatic albumin synthesis. A random-order cross-over study compared the
      effects of Nutrineal (AA source) plus Physioneal (glucose) dialysate with
      Physioneal alone dialysate. Eight patients in the overnight fasting state were
      compared to 12 patients in the daytime-fed state. Fractional albumin synthetic
      rate and whole-body protein synthesis were determined simultaneously using a
      primed-continuous infusion of L-[1-(13)C]-leucine. Fractional albumin synthesis
      on AAs plus glucose dialysis did not differ significantly from that on glucose
      alone in the fasting or the fed state. Protein intake by itself (fed versus
      fasting) failed to induce a significant increase in the fractional synthetic rate
      of albumin. Conversely, the oral protein brought about a significant stimulation
      of whole-body protein synthesis. Our findings show that the supply of AAs has
      different effects on whole-body protein synthesis and the fractional synthetic
      rate of albumin.

PMID- 17554256
TI  - Stability of intact parathyroid hormone in samples from hemodialysis patients.
AB  - The determination of intact parathyroid hormone levels is used for diagnosis and
      in the management of renal osteodystrophy. Pre-analytical and analytical
      conditions are important in the overall confidence of the assay. Unfortunately,
      there are no clear recommendations for the use of serum samples or samples
      anticoagulated with ethylenediaminotetraacetic acid (EDTA) for the best
      preservation of intact parathyroid hormone. In our study, the Roche Elecsys assay
      was used to measure intact hormone in both serum and EDTA plasmas from 16
      hemodialysis patients over the span of a month. Parathyroid hormone stability was
      determined in samples kept frozen for 1-5 days or after 8-24 h at room
      temperature. There was no difference in hormone stability between serum and EDTA
      samples after 1 day in frozen storage. After 5 days frozen, hormone degradation
      was significantly greater after EDTA anticoagulation than in serum aliquots. When
      samples were stored at room temperature, intact parathyroid hormone was
      significantly more stable in EDTA-treated samples than in clotted serum samples,
      especially after 24 h. We conclude that optimum results are achieved in the
      measurement of intact parathyroid hormone levels depending on the workflow of the
      lab. If the lab works with intermittent batches of samples, frozen serum is the
      best. If the lab services general practitioners and/or several hospitals and has
      a continuous flow of samples, EDTA-treated samples stored at room temperature are
      the best.

PMID- 17554257
TI  - Darbepoetin alfa protects podocytes from apoptosis in vitro and in vivo.
AB  - Detachment or apoptosis of podocytes leads to proteinuria and glomerulosclerosis.
      There are no current interventions for diabetic or non-diabetic glomerular
      diseases specifically preventing podocyte apoptosis. Binding of erythropoiesis
      stimulating proteins (ESPs) to receptors on non-hematopoietic cells has been
      shown to have anti-apoptotic effects in vitro, in vivo, and in preliminary human
      studies. Recently, erythropoietin receptors were identified on podocytes;
      therefore, we tested effects of darbepoetin alfa in preventing podocyte
      apoptosis. Cultured immortalized mouse podocytes were treated with low-dose
      ultraviolet-C (uv-C) irradiation to induce apoptosis in the absence or presence
      of darbepoetin alfa. Apoptosis was quantified by Hoechst staining and by caspase
      3 cleavage assessed by Western blots. Pretreatment with darbepoetin alfa
      significantly reduced podocyte apoptosis with this effect involving intact Janus
      family protein kinase-2 (JAK2) and AKT signaling pathways. Additionally,
      darbepoetin alfa was found protective against transforming growth factor-beta1
      but not puromycin aminonucleoside induced apoptosis. Mice with anti-glomerular
      antibody induced glomerulonephritis had significantly less proteinuria,
      glomerulosclerosis, and podocyte apoptosis when treated with darbepoetin alfa.
      Our studies show that treatment of progressive renal diseases characterized by
      podocyte apoptosis with ESPs may be beneficial in slowing progression of chronic
      kidney disease.

PMID- 17554258
TI  - Advanced glycation end products decrease mesangial cell MMP-7: a role in matrix
      accumulation in diabetic nephropathy?
AB  - Increased extracellular matrix material is a pathological hallmark of diabetic
      nephropathy. In addition to collagens, a variety of non-collagenous glycoproteins
      such as fibronectin also accumulate in the kidney of diabetics. The effect of
      diabetes on degradative pathways, in particular those involving non-collagenous
      proteins, are relatively unexplored. In this study, we determined the expression
      of the major matrix metalloproteinase (MMP) responsible for degrading the non
      collagenous matrix glycoprotein fibronectin. Furthermore, the modulation of these
      MMPs by advanced glycation end products (AGE), a key factor in the diabetic
      milieu, was explored. Exposure of mesangial cells to AGEs led to a significant
      reduction in MMP-7, but not MMP-3 or -10. MMP-7 expression was normalized by both
      aminoguanidine, an inhibitor of glycation product formation, or by a neutralizing
      anti-transforming growth factor-beta (TGF-beta) antibody. In streptozotocin
      induced diabetic rats, the diminution in MMP-7 expression and excessive
      fibronectin accumulation were attenuated by aminoguanidine. Humans with type 2
      diabetes and nephropathy displayed similar alterations in MMP-7 to their rodent
      counterparts. Our findings suggest that diminished expression of the glycoprotein
      degrading enzyme, MMP-7, may play a role in fibronectin accumulation in the
      diabetic kidney in response to AGEs and/or TGF-beta.

PMID- 17554259
TI  - The nitrone disodium 2,4-sulphophenyl-N-tert-butylnitrone is without
      cytoprotective effect on sodium nitroprusside-induced cell death in N1E-115
      neuroblastoma cells in vitro.
AB  - Disodium 2,4-sulphophenyl-N-tert-butylnitrone (NXY-059) is a novel free radical
      trapping compound that is neuroprotective in both rodent and primate models of
      acute ischaemic stroke. Neuroprotection in vitro by NXY-059 has not been reported
      previously, and we have now investigated whether such an effect can be detected
      using a simple cell culture model of neurotoxicity. Neuron-like cells of the
      neuroblastoma-derived clonal cell line N1E-115 were exposed to the free radical
      generating agent sodium nitroprusside (SNP), which produced a concentration
      dependent reduction in mitochondrial complex II activity 24 h later (EC(50)
      approximately 100 micromolar). Cell death induced by SNP (100 micromolar),
      assessed either by an increased proportion of apoptotic nuclear morphology or by
      mitochondrial complex II activity, was inhibited by a cocktail of known
      antioxidants (ascorbate, reduced glutathione, and dithiothreitol, all at 100
      micromolar) but not by NXY-059 at a concentration known to be neuroprotective in
      vivo (300 micromolar). Disodium 2,4-sulphophenyl-N-tert-butylnitrone was also
      without effect on H(2)O(2)-mediated cytotoxicity. These results support recent
      data suggesting that in vivo NXY-059 probably acts at the neurovascular unit
      rather than at an intracellular site as a neuroprotective agent.

PMID- 17554260
TI  - Robust associations of four new chromosome regions from genome-wide analyses of
      type 1 diabetes.
AB  - The Wellcome Trust Case Control Consortium (WTCCC) primary genome-wide
      association (GWA) scan on seven diseases, including the multifactorial autoimmune
      disease type 1 diabetes (T1D), shows associations at P < 5 x 10(-7) between T1D
      and six chromosome regions: 12q24, 12q13, 16p13, 18p11, 12p13 and 4q27. Here, we
      attempted to validate these and six other top findings in 4,000 individuals with
      T1D, 5,000 controls and 2,997 family trios independent of the WTCCC study. We
      confirmed unequivocally the associations of 12q24, 12q13, 16p13 and 18p11
      (P(follow-up) <or= 1.35 x 10(-9); P(overall) <or= 1.15 x 10(-14)), leaving eight
      regions with small effects or false-positive associations. We also obtained
      evidence for chromosome 18q22 (P(overall) = 1.38 x 10(-8)) from a GWA study of
      nonsynonymous SNPs. Several regions, including 18q22 and 18p11, showed
      association with autoimmune thyroid disease. This study increases the number of
      T1D loci with compelling evidence from six to at least ten.

PMID- 17554261
TI  - Sequence variants in the autophagy gene IRGM and multiple other replicating loci
      contribute to Crohn's disease susceptibility.
AB  - A genome-wide association scan in individuals with Crohn's disease by the
      Wellcome Trust Case Control Consortium detected strong association at four novel
      loci. We tested 37 SNPs from these and other loci for association in an
      independent case-control sample. We obtained replication for the autophagy
      inducing IRGM gene on chromosome 5q33.1 (replication P = 6.6 x 10(-4), combined P
      = 2.1 x 10(-10)) and for nine other loci, including NKX2-3, PTPN2 and gene
      deserts on chromosomes 1q and 5p13.

PMID- 17554265
TI  - Bad execution.
AB  - China won't achieve a tenable drug regulation policy by hanging public officials.

PMID- 17554266
TI  - Half way to real reform.
AB  - Universities in Germany have undertaken overdue reform, but more change is needed
      to fully tap their potential.

PMID- 17554267
TI  - Community service.
AB  - Introducing three free-access websites for research networking and outreach.

PMID- 17554269
TI  - Bush's climate plan 'nothing new'.

PMID- 17554270
TI  - Simple switch turns cells embryonic.

PMID- 17554271
TI  - DNA reveals how the chicken crossed the sea.

PMID- 17554272
TI  - NASA explores scope for far-flung fix.

PMID- 17554273
TI  - Disgraced official was paid work bonus.

PMID- 17554274
TI  - Genome miners rush to stake claims.

PMID- 17554275
TI  - Terror terms for arsonists.

PMID- 17554276
TI  - Diplomatic talks spur hope in Libya HIV case.

PMID- 17554278
TI  - Sibling rivalry hits Swiss institutes.

PMID- 17554280
TI  - Over a pork barrel.
AB  - The US Congress is well-known for tucking special provisions for favoured
      projects into budget bills. David Goldston explains why 'earmarks' for research
      and development have risen so dramatically in recent years.

PMID- 17554281
TI  - Meeting in the middle.
AB  - Support for copycat versions of biotechnology drugs is growing quickly in the US
      Congress. Meredith Wadman reports.

PMID- 17554282
TI  - Science in Germany: a beacon of reform.

PMID- 17554283
TI  - Primatology: Peaceful primates, violent acts.

PMID- 17554284
TI  - Information from patent office could aid replication.

PMID- 17554285
TI  - Limitations of molecular genetics in conservation.

PMID- 17554286
TI  - Those who are crossing boundaries need less talk, more help and flexibility.

PMID- 17554291
TI  - Determinism: Chaos tamed.
AB  - Even though our view of the physical world has shifted from that of determinism
      to randomness, randomness itself can now be exploited to retrieve a system's
      deterministic response.

PMID- 17554292
TI  - Genomics: guilt by association.

PMID- 17554293
TI  - Spectroscopy: the magic of solenoids.

PMID- 17554294
TI  - Climatology: Tempests in time.

PMID- 17554295
TI  - Stem cells: recycling the abnormal.

PMID- 17554297
TI  - Astrophysics: gravitational waves constrained.

PMID- 17554298
TI  - Obituary: Theodore H. Maiman (1927-2007).

PMID- 17554299
TI  - Replicating genotype-phenotype associations.

PMID- 17554301
TI  - Developmental reprogramming after chromosome transfer into mitotic mouse zygotes.
AB  - Until now, animal cloning and the production of embryonic stem cell lines by
      somatic cell nuclear transfer have relied on introducing nuclei into meiotic
      oocytes. In contrast, attempts at somatic cell nuclear transfer into fertilized
      interphase zygotes have failed. As a result, it has generally been assumed that
      unfertilized human oocytes will be required for the generation of tailored human
      embryonic stem cell lines from patients by somatic cell nuclear transfer. Here we
      report, however, that, unlike interphase zygotes, mouse zygotes temporarily
      arrested in mitosis can support somatic cell reprogramming, the production of
      embryonic stem cell lines and the full-term development of cloned animals. Thus,
      human zygotes and perhaps human embryonic blastomeres may be useful supplements
      to human oocytes for the creation of patient-derived human embryonic stem cells.

PMID- 17554302
TI  - DNA repair is limiting for haematopoietic stem cells during ageing.
AB  - Accumulation of DNA damage leading to adult stem cell exhaustion has been
      proposed to be a principal mechanism of ageing. Here we address this question by
      taking advantage of the highly specific role of DNA ligase IV in the repair of
      DNA double-strand breaks by non-homologous end-joining, and by the discovery of a
      unique mouse strain with a hypomorphic Lig4(Y288C) mutation. The Lig4(Y288C)
      mouse, identified by means of a mutagenesis screening programme, is a mouse model
      for human LIG4 syndrome, showing immunodeficiency and growth retardation.
      Diminished DNA double-strand break repair in the Lig4(Y288C) strain causes a
      progressive loss of haematopoietic stem cells and bone marrow cellularity during
      ageing, and severely impairs stem cell function in tissue culture and
      transplantation. The sensitivity of haematopoietic stem cells to non-homologous
      end-joining deficiency is therefore a key determinant of their ability to
      maintain themselves against physiological stress over time and to withstand
      culture and transplantation.

PMID- 17554303
TI  - High-resolution, high-sensitivity NMR of nanolitre anisotropic samples by coil
      spinning.
AB  - Nuclear magnetic resonance (NMR) can probe the local structure and dynamic
      properties of liquids and solids, making it one of the most powerful and
      versatile analytical methods available today. However, its intrinsically low
      sensitivity precludes NMR analysis of very small samples-as frequently used when
      studying isotopically labelled biological molecules or advanced materials, or as
      preferred when conducting high-throughput screening of biological samples or 'lab
      on-a-chip' studies. The sensitivity of NMR has been improved by using static
      micro-coils, alternative detection schemes and pre-polarization approaches. But
      these strategies cannot be easily used in NMR experiments involving the fast
      sample spinning essential for obtaining well-resolved spectra from non-liquid
      samples. Here we demonstrate that inductive coupling allows wireless transmission
      of radio-frequency pulses and the reception of NMR signals under fast spinning of
      both detector coil and sample. This enables NMR measurements characterized by an
      optimal filling factor, very high radio-frequency field amplitudes and enhanced
      sensitivity that increases with decreasing sample volume. Signals obtained for
      nanolitre-sized samples of organic powders and biological tissue increase by
      almost one order of magnitude (or, equivalently, are acquired two orders of
      magnitude faster), compared to standard NMR measurements. Our approach also
      offers optimal sensitivity when studying samples that need to be confined inside
      multiple safety barriers, such as radioactive materials. In principle, the co
      rotation of a micrometre-sized detector coil with the sample and the use of
      inductive coupling (techniques that are at the heart of our method) should enable
      highly sensitive NMR measurements on any mass-limited sample that requires fast
      mechanical rotation to obtain well-resolved spectra. The method is easy to
      implement on a commercial NMR set-up and exhibits improved performance with
      miniaturization, and we accordingly expect that it will facilitate the
      development of novel solid-state NMR methodologies and find wide use in high
      throughput chemical and biomedical analysis.

PMID- 17554304
TI  - Low Atlantic hurricane activity in the 1970s and 1980s compared to the past 270
      years.
AB  - Hurricane activity in the North Atlantic Ocean has increased significantly since
      1995 (refs 1, 2). This trend has been attributed to both anthropogenically
      induced climate change and natural variability, but the primary cause remains
      uncertain. Changes in the frequency and intensity of hurricanes in the past can
      provide insights into the factors that influence hurricane activity, but reliable
      observations of hurricane activity in the North Atlantic only cover the past few
      decades. Here we construct a record of the frequency of major Atlantic hurricanes
      over the past 270 years using proxy records of vertical wind shear and sea
      surface temperature (the main controls on the formation of major hurricanes in
      this region) from corals and a marine sediment core. The record indicates that
      the average frequency of major hurricanes decreased gradually from the 1760s
      until the early 1990s, reaching anomalously low values during the 1970s and
      1980s. Furthermore, the phase of enhanced hurricane activity since 1995 is not
      unusual compared to other periods of high hurricane activity in the record and
      thus appears to represent a recovery to normal hurricane activity, rather than a
      direct response to increasing sea surface temperature. Comparison of the record
      with a reconstruction of vertical wind shear indicates that variability in this
      parameter primarily controlled the frequency of major hurricanes in the Atlantic
      over the past 270 years, suggesting that changes in the magnitude of vertical
      wind shear will have a significant influence on future hurricane activity.

PMID- 17554305
TI  - Boron and oxygen isotope evidence for recycling of subducted components over the
      past 2.5 Gyr.
AB  - Evidence for the deep recycling of surficial materials through the Earth's mantle
      and their antiquity has long been sought to understand the role of subducting
      plates and plumes in mantle convection. Radiogenic isotope evidence for such
      recycling remains equivocal because the age and location of parent-daughter
      fractionation are not known. Conversely, while stable isotopes can provide
      irrefutable evidence for low-temperature fractionation, their range in most
      unaltered oceanic basalts is limited and the age of any variation is
      unconstrained. Here we show that delta(18)O ratios in basalts from the Azores are
      often lower than in pristine mantle. This, combined with increased Nb/B ratios
      and a large range in delta(11)B ratios, provides compelling evidence for the
      recycling of materials that had undergone fractionation near the Earth's surface.
      Moreover, delta(11)B is negatively correlated with (187)Os/(188)Os ratios, which
      extend to subchondritic values, constraining the age of the high Nb/B, (11)B
      enriched endmember to be more than 2.5 billion years (Gyr) old. We infer this
      component to be melt- and fluid-depleted lithospheric mantle from a subducted
      oceanic plate, whereas other Azores basalts contain a contribution from
      approximately 3-Gyr-old melt-enriched basalt. We conclude that both components
      are most probably derived from an Archaean oceanic plate that was subducted,
      arguably into the deep mantle, where it was stored until thermal buoyancy caused
      it to rise beneath the Azores islands approximately 3 Gyr later.

PMID- 17554300
TI  - Genome-wide association study of 14,000 cases of seven common diseases and 3,000
      shared controls.
AB  - There is increasing evidence that genome-wide association (GWA) studies represent
      a powerful approach to the identification of genes involved in common human
      diseases. We describe a joint GWA study (using the Affymetrix GeneChip 500K
      Mapping Array Set) undertaken in the British population, which has examined
      approximately 2,000 individuals for each of 7 major diseases and a shared set of
      approximately 3,000 controls. Case-control comparisons identified 24 independent
      association signals at P < 5 x 10(-7): 1 in bipolar disorder, 1 in coronary
      artery disease, 9 in Crohn's disease, 3 in rheumatoid arthritis, 7 in type 1
      diabetes and 3 in type 2 diabetes. On the basis of prior findings and replication
      studies thus-far completed, almost all of these signals reflect genuine
      susceptibility effects. We observed association at many previously identified
      loci, and found compelling evidence that some loci confer risk for more than one
      of the diseases studied. Across all diseases, we identified a large number of
      further signals (including 58 loci with single-point P values between 10(-5) and
      5 x 10(-7)) likely to yield additional susceptibility loci. The importance of
      appropriately large samples was confirmed by the modest effect sizes observed at
      most loci identified. This study thus represents a thorough validation of the GWA
      approach. It has also demonstrated that careful use of a shared control group
      represents a safe and effective approach to GWA analyses of multiple disease
      phenotypes; has generated a genome-wide genotype database for future studies of
      common diseases in the British population; and shown that, provided individuals
      with non-European ancestry are excluded, the extent of population stratification
      in the British population is generally modest. Our findings offer new avenues for
      exploring the pathophysiology of these important disorders. We anticipate that
      our data, results and software, which will be widely available to other
      investigators, will provide a powerful resource for human genetics research.

PMID- 17554306
TI  - Pollinator shifts drive increasingly long nectar spurs in columbine flowers.
AB  - Directional evolutionary trends have long garnered interest because they suggest
      that evolution can be predictable. However, the identification of the trends
      themselves and the underlying processes that may produce them have often been
      controversial. In 1862, in explaining the exceptionally long nectar spur of
      Angraecum sesquipedale, Darwin proposed that a coevolutionary 'race' had driven
      the directional increase in length of a plant's spur and its pollinator's tongue.
      Thus he predicted the existence of an exceptionally long-tongued moth. Though the
      discovery of Xanthopan morgani ssp. praedicta in 1903 with a tongue length of 22
      cm validated Darwin's prediction, his 'race' model for the evolution of long
      spurred flowers remains contentious. Spurs may also evolve to exceptional lengths
      by way of pollinator shifts as plants adapt to a series of unrelated pollinators,
      each with a greater tongue length. Here, using a species-level phylogeny of the
      columbine genus, Aquilegia, we show a significant evolutionary trend for
      increasing spur length during directional shifts to pollinators with longer
      tongues. In addition, we find evidence for 'punctuated' change in spur length
      during speciation events, suggesting that Aquilegia nectar spurs rapidly evolve
      to fit adaptive peaks predefined by pollinator morphology. These findings show
      that evolution may proceed in predictable pathways without reversals and that
      change may be concentrated during speciation.

PMID- 17554307
TI  - The medaka draft genome and insights into vertebrate genome evolution.
AB  - Teleosts comprise more than half of all vertebrate species and have adapted to a
      variety of marine and freshwater habitats. Their genome evolution and
      diversification are important subjects for the understanding of vertebrate
      evolution. Although draft genome sequences of two pufferfishes have been
      published, analysis of more fish genomes is desirable. Here we report a high
      quality draft genome sequence of a small egg-laying freshwater teleost, medaka
      (Oryzias latipes). Medaka is native to East Asia and an excellent model system
      for a wide range of biology, including ecotoxicology, carcinogenesis, sex
      determination and developmental genetics. In the assembled medaka genome (700
      megabases), which is less than half of the zebrafish genome, we predicted 20,141
      genes, including approximately 2,900 new genes, using 5'-end serial analysis of
      gene expression tag information. We found single nucleotide polymorphisms (SNPs)
      at an average rate of 3.42% between the two inbred strains derived from two
      regional populations; this is the highest SNP rate seen in any vertebrate
      species. Analyses based on the dense SNP information show a strict genetic
      separation of 4 million years (Myr) between the two populations, and suggest that
      differential selective pressures acted on specific gene categories. Four-way
      comparisons with the human, pufferfish (Tetraodon), zebrafish and medaka genomes
      revealed that eight major interchromosomal rearrangements took place in a
      remarkably short period of approximately 50 Myr after the whole-genome
      duplication event in the teleost ancestor and afterwards, intriguingly, the
      medaka genome preserved its ancestral karyotype for more than 300 Myr.

PMID- 17554308
TI  - Dscam2 mediates axonal tiling in the Drosophila visual system.
AB  - Sensory processing centres in both the vertebrate and the invertebrate brain are
      often organized into reiterated columns, thus facilitating an internal
      topographic representation of the external world. Cells within each column are
      arranged in a stereotyped fashion and form precise patterns of synaptic
      connections within discrete layers. These connections are largely confined to a
      single column, thereby preserving the spatial information from the periphery.
      Other neurons integrate this information by connecting to multiple columns.
      Restricting axons to columns is conceptually similar to tiling. Axons and
      dendrites of neighbouring neurons of the same class use tiling to form complete,
      yet non-overlapping, receptive fields. It is thought that, at the molecular
      level, cell-surface proteins mediate tiling through contact-dependent repulsive
      interactions, but proteins serving this function have not yet been identified.
      Here we show that the immunoglobulin superfamily member Dscam2 restricts the
      connections formed by L1 lamina neurons to columns in the Drosophila visual
      system. Our data support a model in which Dscam2 homophilic interactions mediate
      repulsion between neurites of L1 cells in neighbouring columns. We propose that
      Dscam2 is a tiling receptor for L1 neurons.

PMID- 17554309
TI  - Deficiencies in DNA damage repair limit the function of haematopoietic stem cells
      with age.
AB  - A diminished capacity to maintain tissue homeostasis is a central physiological
      characteristic of ageing. As stem cells regulate tissue homeostasis, depletion of
      stem cell reserves and/or diminished stem cell function have been postulated to
      contribute to ageing. It has further been suggested that accumulated DNA damage
      could be a principal mechanism underlying age-dependent stem cell decline. We
      have tested these hypotheses by examining haematopoietic stem cell reserves and
      function with age in mice deficient in several genomic maintenance pathways
      including nucleotide excision repair, telomere maintenance and non-homologous end
      joining. Here we show that although deficiencies in these pathways did not
      deplete stem cell reserves with age, stem cell functional capacity was severely
      affected under conditions of stress, leading to loss of reconstitution and
      proliferative potential, diminished self-renewal, increased apoptosis and,
      ultimately, functional exhaustion. Moreover, we provide evidence that endogenous
      DNA damage accumulates with age in wild-type stem cells. These data are
      consistent with DNA damage accrual being a physiological mechanism of stem cell
      ageing that may contribute to the diminished capacity of aged tissues to return
      to homeostasis after exposure to acute stress or injury.

PMID- 17554310
TI  - The ATM repair pathway inhibits RNA polymerase I transcription in response to
      chromosome breaks.
AB  - DNA lesions interfere with DNA and RNA polymerase activity. Cyclobutane
      pyrimidine dimers and photoproducts generated by ultraviolet irradiation cause
      stalling of RNA polymerase II, activation of transcription-coupled repair
      enzymes, and inhibition of RNA synthesis. During the S phase of the cell cycle,
      collision of replication forks with damaged DNA blocks ongoing DNA replication
      while also triggering a biochemical signal that suppresses the firing of distant
      origins of replication. Whether the transcription machinery is affected by the
      presence of DNA double-strand breaks remains a long-standing question. Here we
      monitor RNA polymerase I (Pol I) activity in mouse cells exposed to genotoxic
      stress and show that induction of DNA breaks leads to a transient repression in
      Pol I transcription. Surprisingly, we find Pol I inhibition is not itself the
      direct result of DNA damage but is mediated by ATM kinase activity and the repair
      factor proteins NBS1 (also known as NLRP2) and MDC1. Using live-cell imaging,
      laser micro-irradiation, and photobleaching technology we demonstrate that DNA
      lesions interfere with Pol I initiation complex assembly and lead to a premature
      displacement of elongating holoenzymes from ribosomal DNA. Our data reveal a
      novel ATM/NBS1/MDC1-dependent pathway that shuts down ribosomal gene
      transcription in response to chromosome breaks.

PMID- 17554311
TI  - Control of DNA methylation and heterochromatic silencing by histone H2B
      deubiquitination.
AB  - Epigenetic regulation involves reversible changes in DNA methylation and/or
      histone modification patterns. Short interfering RNAs (siRNAs) can direct DNA
      methylation and heterochromatic histone modifications, causing sequence-specific
      transcriptional gene silencing. In animals and yeast, histone H2B is known to be
      monoubiquitinated, and this regulates the methylation of histone H3 (refs 10,
      11). However, the relationship between histone ubiquitination and DNA methylation
      has not been investigated. Here we show that mutations in an Arabidopsis
      deubiquitination enzyme, SUP32/UBP26, decrease the dimethylation on lysine 9 of
      H3, suppress siRNA-directed methylation of DNA and release heterochromatic
      silencing of transgenes as well as transposons. We found that Arabidopsis histone
      H2B is monoubiquitinated at lysine 143 and that the levels of ubiquitinated H2B
      and trimethyl H3 at lysine 4 increase in sup32 mutant plants. SUP32/UBP26 can
      deubiquitinate H2B, and chromatin immunoprecipitation assays suggest an
      association between H2B ubiquitination and release of silencing. These data
      suggest that H2B deubiquitination by SUP32/UBP26 is required for heterochromatic
      histone H3 methylation and DNA methylation.

PMID- 17554312
TI  - Antibodies: The generation game.
AB  - Proteomics is hungry for well-validated antibodies. Nathan Blow looks at the
      options and sees how researchers are redefining the way to generate an antibody.

PMID- 17554313
TI  - Antibodies: antibodies in the fast lane.

PMID- 17554315
TI  - The young and the restless.

PMID- 17554316
TI  - Sluggish approvals blocking Africans' access to bed nets.

PMID- 17554317
TI  - Emergency trials of blood substitutes skirt ethical questions.

PMID- 17554319
TI  - London hospital launches infectious disease 'biobank'.

PMID- 17554320
TI  - Fertility clinics cashing in on risky immune tests, expert warns.

PMID- 17554321
TI  - AIDS vaccine group expands operations in New York.

PMID- 17554322
TI  - Profile: Peter Doherty.

PMID- 17554324
TI  - Paging all doctors.

PMID- 17554326
TI  - Reply to 'Salusins: newly identified bioactive peptides with hemodynamic and
      mitogenic activities'.

PMID- 17554327
TI  - Reply to 'Critics slam Russian trial to test pig pancreas for diabetes'.

PMID- 17554329
TI  - Heme moves to center stage in cerebral malaria.

PMID- 17554330
TI  - Linking calcineurin activity to leukemogenesis.

PMID- 17554331
TI  - Retinaldehyde: more than meets the eye.

PMID- 17554332
TI  - The hydrogen highway to reperfusion therapy.

PMID- 17554333
TI  - HER3 and mutant EGFR meet MET.

PMID- 17554335
TI  - The US pandemic influenza implementation plan at six months.

PMID- 17554336
TI  - In vitro reprogramming of fibroblasts into a pluripotent ES-cell-like state.
AB  - Nuclear transplantation can reprogramme a somatic genome back into an embryonic
      epigenetic state, and the reprogrammed nucleus can create a cloned animal or
      produce pluripotent embryonic stem cells. One potential use of the nuclear
      cloning approach is the derivation of 'customized' embryonic stem (ES) cells for
      patient-specific cell treatment, but technical and ethical considerations impede
      the therapeutic application of this technology. Reprogramming of fibroblasts to a
      pluripotent state can be induced in vitro through ectopic expression of the four
      transcription factors Oct4 (also called Oct3/4 or Pou5f1), Sox2, c-Myc and Klf4.
      Here we show that DNA methylation, gene expression and chromatin state of such
      induced reprogrammed stem cells are similar to those of ES cells. Notably, the
      cells-derived from mouse fibroblasts-can form viable chimaeras, can contribute to
      the germ line and can generate live late-term embryos when injected into
      tetraploid blastocysts. Our results show that the biological potency and
      epigenetic state of in-vitro-reprogrammed induced pluripotent stem cells are
      indistinguishable from those of ES cells.

PMID- 17554338
TI  - Generation of germline-competent induced pluripotent stem cells.
AB  - We have previously shown that pluripotent stem cells can be induced from mouse
      fibroblasts by retroviral introduction of Oct3/4 (also called Pou5f1), Sox2, c
      Myc and Klf4, and subsequent selection for Fbx15 (also called Fbxo15) expression.
      These induced pluripotent stem (iPS) cells (hereafter called Fbx15 iPS cells) are
      similar to embryonic stem (ES) cells in morphology, proliferation and teratoma
      formation; however, they are different with regards to gene expression and DNA
      methylation patterns, and fail to produce adult chimaeras. Here we show that
      selection for Nanog expression results in germline-competent iPS cells with
      increased ES-cell-like gene expression and DNA methylation patterns compared with
      Fbx15 iPS cells. The four transgenes (Oct3/4, Sox2, c-myc and Klf4) were strongly
      silenced in Nanog iPS cells. We obtained adult chimaeras from seven Nanog iPS
      cell clones, with one clone being transmitted through the germ line to the next
      generation. Approximately 20% of the offspring developed tumours attributable to
      reactivation of the c-myc transgene. Thus, iPS cells competent for germline
      chimaeras can be obtained from fibroblasts, but retroviral introduction of c-Myc
      should be avoided for clinical application.

PMID- 17554337
TI  - A microRNA component of the p53 tumour suppressor network.
AB  - A global decrease in microRNA (miRNA) levels is often observed in human cancers,
      indicating that small RNAs may have an intrinsic function in tumour suppression.
      To identify miRNA components of tumour suppressor pathways, we compared miRNA
      expression profiles of wild-type and p53-deficient cells. Here we describe a
      family of miRNAs, miR-34a-c, whose expression reflected p53 status. Genes
      encoding miRNAs in the miR-34 family are direct transcriptional targets of p53,
      whose induction by DNA damage and oncogenic stress depends on p53 both in vitro
      and in vivo. Ectopic expression of miR-34 induces cell cycle arrest in both
      primary and tumour-derived cell lines, which is consistent with the observed
      ability of miR-34 to downregulate a programme of genes promoting cell cycle
      progression. The p53 network suppresses tumour formation through the coordinated
      activation of multiple transcriptional targets, and miR-34 may act in concert
      with other effectors to inhibit inappropriate cell proliferation.

PMID- 17554339
TI  - Akt/PKB regulates hepatic metabolism by directly inhibiting PGC-1alpha
      transcription coactivator.
AB  - Type 2 diabetes mellitus, a disease with significant effects on the health and
      economy of Western societies, involves disturbances in both lipid and
      carbohydrate metabolism. In the insulin-resistant or diabetic state, the liver is
      unresponsive to the actions of insulin with regard to the suppression of glucose
      output but continues to produce large amounts of lipid, the latter mimicking the
      fed, insulin-replete condition. The disordered distribution of lipids contributes
      to the cardiovascular disease that is the greatest cause of mortality of type 2
      diabetes mellitus. Yet the precise signal transduction pathways by which insulin
      regulates hepatic lipid synthesis and degradation remain largely unknown. Here we
      describe a mechanism by which insulin, through the intermediary protein kinase
      Akt2/protein kinase B (PKB)-beta, elicits the phosphorylation and inhibition of
      the transcriptional coactivator peroxisome proliferator-activated receptor
      coactivator 1alpha (PGC-1alpha), a global regulator of hepatic metabolism during
      fasting. Phosphorylation prevents the recruitment of PGC-1alpha to the cognate
      promoters, impairing its ability to promote gluconeogenesis and fatty acid
      oxidation. These results define a mechanism by which insulin controls lipid
      catabolism in the liver and suggest a novel site for therapy in type 2 diabetes
      mellitus.

PMID- 17554340
TI  - Treatment of diabetes and atherosclerosis by inhibiting fatty-acid-binding
      protein aP2.
AB  - Adipocyte fatty-acid-binding protein, aP2 (FABP4) is expressed in adipocytes and
      macrophages, and integrates inflammatory and metabolic responses. Studies in aP2
      deficient mice have shown that this lipid chaperone has a significant role in
      several aspects of metabolic syndrome, including type 2 diabetes and
      atherosclerosis. Here we demonstrate that an orally active small-molecule
      inhibitor of aP2 is an effective therapeutic agent against severe atherosclerosis
      and type 2 diabetes in mouse models. In macrophage and adipocyte cell lines with
      or without aP2, we also show the target specificity of this chemical intervention
      and its mechanisms of action on metabolic and inflammatory pathways. Our findings
      demonstrate that targeting aP2 with small-molecule inhibitors is possible and can
      lead to a new class of powerful therapeutic agents to prevent and treat metabolic
      diseases such as type 2 diabetes and atherosclerosis.

PMID- 17554342
TI  - A polymorphism in human TLR2 is associated with increased susceptibility to
      tuberculous meningitis.
AB  - Tuberculous meningitis (TBM) results from the haematogenous dissemination of
      Mycobacterium tuberculosis from the lung to the brain. Dissemination is believed
      to occur early during infection, before the development of adaptive immunity.
      Toll-like receptor 2 (TLR2) mediates recognition of M. tuberculosis and initiates
      the innate immune response to infection. We hypothesized that polymorphisms in
      the TLR2 gene influence bacterial dissemination and the development of TBM. A
      case-control study was designed to test the hypothesis. Cases of
      bacteriologically confirmed pulmonary tuberculosis (TB) (n=183) and TBM (n=175),
      and cord blood controls (n=389) were enrolled in Vietnam. TLR2 genotype 597CC was
      associated with susceptibility to TB (odds ratio (OR)=2.22, 95% confidence
      interval (CI): 1.23-3.99). The association was found with meningeal rather than
      pulmonary TB (TBM vs control, OR=3.26, 95% CI: 1.72-6.18), and was strongest when
      miliary TB was found on chest radiography (controls vs TBM with miliary TB,
      OR=5.28, 95% CI: 2.20-12.65). Furthermore, the association increased with the
      severity of neurologic symptoms (grade I TBM, OR=1.93, 95% CI: 0.54-6.92; grade
      II, OR=3.32, 95% CI: 0.84-13.2; and grade III, OR=5.70, 95% CI: 1.81-18.0). These
      results demonstrate a strong association of TLR2 SNP T597C with the development
      of TBM and miliary TB and indicate that TLR2 influences the dissemination of M.
      tuberculosis.

PMID- 17554341
TI  - SUMO4 M55V polymorphism affects susceptibility to type I diabetes in HLA DR3- and
      DR4-positive Swedish patients.
AB  - SUMO4 M55V, located in IDDM5, has been a focus for debate because of its
      association to type I diabetes (TIDM) in Asians but not in Caucasians. The
      current study aims to test the significance of M55V association to TIDM in a
      large cohort of Swedish Caucasians, and to test whether M55V is associated in
      those carrying human leukocyte antigen (HLA) class II molecules. A total of 673
      TIDM patients and 535 age- and sex-matched healthy controls were included in the
      study. PCR-RFLP was performed to identify the genotype and allele variations. Our
      data suggest that SUMO4 M55V is not associated with susceptibility to TIDM by
      itself. When we stratified our patients and controls based on heterozygosity for
      HLA-DR3/DR4 and SUMO4 genotypes, we found that presence of SUMO4 GG increased
      further the relative risk conferred by HLA-DR3/DR4 to TIDM, whereas SUMO4 AA
      decreased the risk. From the current study, we conclude that SUMO4 M55V is
      associated with TIDM in association with high-risk HLA-DR3 and DR4, but not by
      itself.

PMID- 17554343
TI  - Controlled diastolic blood pressure, previous stroke and associated risk factors
      are obstacles to improving systolic blood pressure.

PMID- 17554344
TI  - Alcohol and cigarette consumption, renal function and blood pressure in middle
      aged healthy men.

PMID- 17554345
TI  - Treatment of hypertension with olmesartan medoxomil, alone and in combination
      with a diuretic: an update.
AB  - Olmesartan medoxomil is an angiotensin II (Ang II) receptor blocker (ARB) that
      has been approved by the US Food and Drug Administration (FDA) for the treatment
      of hypertension. It is a prodrug that is hydrolysed in the gut into its active
      metabolite, olmesartan (RNH-6270). Olmesartan is highly selective for the Ang II
      type 1 receptor (AT1) to which it binds completely and insurmountably and has
      very little affinity for the other receptor subtypes AT2 and AT4. After oral
      administration, in animals and humans, it achieves a maximal blood drug
      concentration within a maximal time of approximately 2 h. It is then slowly
      eliminated in the urine and faeces. His half-life is approximately 13 h, which
      makes it suitable for once-daily administration. Olmesartan medoxomil given
      orally in single daily doses of 20-40 mg has demonstrated significant blood
      pressure (BP) lowering effects in hypertensive patients. A medline search for the
      preparation of this manuscript was conducted and revealed 128 references, from
      2000 to 2007. Of these, only 16 well-designed prospective clinical trials were
      selected. The remaining were either animal studies, reviews or studies in
      progress. In well-designed clinical trials, olmesartan medoxomil has demonstrated
      similar antihypertensive actions to the other antihypertensive drugs, as well as
      other members of its class given the highest recommended doses. In addition, the
      BP lowering effect of olmesartan, like the other members of its class, is greatly
      enhanced in combination with a diuretic. Its safety profile is similar to the
      other ARBs and no different than placebo.

PMID- 17554347
TI  - Thirst, and (bottled) water everywhere.

PMID- 17554348
TI  - Very early alloantigen-independent trafficking of lymphocytes during ischemic
      acute kidney injury.
AB  - Lymphocytes play an important role during ischemia-reperfusion injury (IRI). Lai
      et al. have demonstrated, for the first time, an increase in kidney lymphocytes 1
      hour after IRI, a newly identified kidney lymphocyte reservoir, and have
      confirmed the pathogenic role of lymphocytes by manipulating the sphingosine-1
      phosphate (SIP)-sphingosine-1-phosphate type 1 (S1P1) receptor pathway.

PMID- 17554349
TI  - Adiponectin and renal disease progression: another epidemiologic conundrum?
AB  - In an analysis based on the Mild to Moderate Kidney Disease (MMKD) study,
      adiponectin, a pleiotropic, insulin-sensitizing, anti-inflammatory and vasculo
      protective cytokine, was directly related to renal disease progression. The
      precise definition of this apparently paradoxical association now requires that
      the research focus be moved from the study database to the experimental
      laboratory.

PMID- 17554350
TI  - Malignancy after kidney transplantation: still a challenge.
AB  - Long-term complications of continuous immunosuppression still remain a serious
      threat and are currently drawing the attention of transplant physicians. Wimmer
      et al. show that malignancy occurs approximately fourfold more frequently in
      renal-transplant recipients than in a normal control population. Besides
      immunosuppression, viruses probably play an important oncogenic role in
      transplant recipients. The retrospective analysis by Wimmer et al. suggests that
      mTOR inhibitors and interleukin-2 receptor antibodies are promising
      immunosuppressive drugs to reduce the risk of cancer after transplantation. These
      preliminary results must be confirmed in large, prospective, randomized,
      controlled trials, with long follow-up, designed to evaluate the incidence of de
      novo malignancy in transplant recipients.

PMID- 17554351
TI  - Diabetic nephropathy and proximal tubule ROS: challenging our
      glomerulocentricity.
AB  - Diabetic nephropathy is currently viewed as a predominantly glomerular process
      with glomerular injury driving secondary tubular loss. Brezniceanu and colleagues
      apply transgenic methods to support a prominent role for reactive oxygen species
      as mediators and for the proximal tubule as a major site of early disease
      activity in diabetes. Results support evidence for early tubular apoptosis and
      atrophy in human diabetic nephropathy.

PMID- 17554353
TI  - Reemergence of the maxi K+ as a K+ secretory channel.

PMID- 17554356
TI  - Parathyroid hormone synthesis suppression by 25(OH)2 vit D3.

PMID- 17554357
TI  - Adynamic bone disease and malnutrition-inflammation-cachexia syndrome.

PMID- 17554358
TI  - Don't be so BOLD: potential limitations in the use of BOLD MRI for studies of
      renal oxygenation.

PMID- 17554361
TI  - Does Sevelamer reduce mortality by slowing of progression of coronary
      calcification?

PMID- 17554362
TI  - White star in the black sea: an unusual stone associated with ureteropelvic
      junction obstruction.

PMID- 17554363
TI  - Multiple self-healing squamous epithelioma in different ethnic groups: more than
      a founder mutation disorder?
AB  - Multiple self-healing squamous epithelioma (MSSE), also known as Ferguson-Smith
      Disease, is a rare cancer-associated genodermatosis with an autosomal dominant
      inheritance. Affected patients suffer from recurrent skin lesions, which
      clinically and histologically resemble keratoacanthomas or well-differentiated
      squamous cell carcinomas, but which, if left, undergo spontaneous regression,
      leaving pronounced scarring. The majority of MSSE cases previously described were
      of Scottish ancestry and all shared the same at-risk haplotype, suggesting that
      this disorder was caused by a founder mutation. The candidate locus for MSSE lies
      in a region of <4 cM in chromosome 9q22, between the markers D9S197 and D9S1809.
      We recently investigated MSSE families of non-Scottish origin. For every patient
      of these families, we obtained a detailed clinical history, with particular
      attention to the age of onset, distribution, and clinical course of their skin
      lesions. Once confirmed that they were really affected by MSSE, we performed
      haplotype analysis on them and their families. The haplotypes for polymorphic
      markers segregating with MSSE in non-Scottish and Scottish families differ,
      suggesting that MSSE is not caused by a founder mutation and might be more common
      than originally thought.

PMID- 17554364
TI  - Stratum corneum acidification is impaired in moderately aged human and murine
      skin.
AB  - Aged skin commonly is afflicted by inflammatory skin diseases or xerosis/eczema
      that could be triggered or exacerbated by impaired epidermal permeability barrier
      homeostasis. This defect is linked to reduced epidermal lipid synthesis in humans
      and in mice of advanced age (i.e., >75 years in human or >18-24 months in mice).
      We now report that barrier defects in moderately aged humans (50-80 years) or
      analogously aged mice (12-15 months) are linked instead to defective stratum
      corneum (SC) acidity. In moderately aged mouse epidermis, we find that abnormal
      acidification, in turn, is linked to decreased Na+/H+ antiporter (NHE1)
      expression. Decreased NHE1 levels lead to increased SC pH, which results in
      defective lipid processing and delayed maturation of lamellar membranes, due to
      suboptimal activation of the pH-sensitive essential, lipid-processing enzyme,
      beta-glucocerebrosidase. Conversely, impaired SC integrity in moderately aged
      mice is due to increased pH-dependent activation of serine proteases, leading to
      premature degradation of corneodesmosomes. These abnormalities were normalized by
      exogenously acidifying the SC, suggesting a basis for the well-known
      acidification therapies that are widely used to treat the pathologic
      xerosis/eczema seen in moderately aged humans.

PMID- 17554365
TI  - Dual-channel two-photon microscopy study of transdermal transport in skin treated
      with low-frequency ultrasound and a chemical enhancer.
AB  - Visualization of transdermal permeant pathways is necessary to substantiate model
      based conclusions drawn using permeability data. The aim of this investigation
      was to visualize the transdermal delivery of sulforhodamine B (SRB), a
      fluorescent hydrophilic permeant, and of rhodamine B hexyl ester (RBHE), a
      fluorescent hydrophobic permeant, using dual-channel two-photon microscopy (TPM)
      to better understand the transport pathways and the mechanisms of enhancement in
      skin treated with low-frequency ultrasound (US) and/or a chemical enhancer
      (sodium lauryl sulfate--SLS) relative to untreated skin (the control). The
      results demonstrate that (1) both SRB and RBHE penetrate beyond the stratum
      corneum and into the viable epidermis only in discrete regions (localized
      transport regions--LTRs) of US treated and of US/SLS-treated skin, (2) a chemical
      enhancer is required in the coupling medium during US treatment to obtain two
      significant levels of increased penetration of SRB and RBHE in US-treated skin
      relative to untreated skin, and (3) transcellular pathways are present in the
      LTRs of US treated and of US/SLS-treated skin for SRB and RBHE, and in SLS
      treated skin for SRB. In summary, the skin is greatly perturbed in the LTRs of US
      treated and US/SLS-treated skin with chemical enhancers playing a significant
      role in US-mediated transdermal drug delivery.

PMID- 17554366
TI  - Involvement of protein kinase A in nitric oxide stimulating effect on a BK(Ca)
      channel of human dermal fibroblasts.
AB  - We reported previously that a large-conductance Ca2+-activated K+ (BK(Ca))
      channel constitutes a significant fraction of the K+ current in human dermal
      fibroblasts, and that nitric oxide (NO) increases the open-channel probability
      (NPo) of BK(Ca) channels via a soluble guanylate cyclase (sGC)/cyclic guanosine
      monophosphate (cGMP)/protein kinase G (PKG) pathway. The purpose of this study
      was to investigate whether the adenylate cyclase (AC)/cAMP/protein kinase A (PKA)
      pathway may also be involved in NO action on BK(Ca) channels in human dermal
      fibroblasts. Electrophysiological single-channel recordings were performed on
      fifth-passage cells of human penile skin cultures. KT5720 (specific PKA
      inhibitor) blocked the stimulatory effect of sodium nitroprusside (NO donor) on
      BK(Ca) channels. By contrast, forskolin (AC activator) or 8-bromo-cAMP (cell
      permeable cAMP analog) did not increase the NPo of the channel. The PKA catalytic
      subunit (PKAcs) alone did not increase the NPo of the channel in cell-attached
      and inside-out patches, however, PKAcs with cGMP increased the NPo. In contrast,
      PKAcs with cGMP did not increase the NPo of BK(Ca) channels with 1H-[1,2,4]
      oxadiazolo[4,3-a]quinoxalin-1-one pretreatment, and KT5720 pretreatment also
      blocked the stimulatory effect of 8-Br-cGMP. In conclusion, the present data
      suggest the involvement of PKA in the stimulatory effect of NO on the BK(Ca)
      channel in human dermal fibroblasts through cGMP.

PMID- 17554367
TI  - Cellular defects in Chediak-Higashi syndrome correlate with the molecular
      genotype and clinical phenotype.

PMID- 17554368
TI  - Polymorphisms in interleukin-15 gene on chromosome 4q31.2 are associated with
      psoriasis vulgaris in Chinese population.
AB  - Through a series of linkage analyses in a large Chinese family cohort of
      psoriasis, we previously identified and confirmed a non-HLA psoriasis linkage
      locus PSORS9 within a small region at 4q31.2-32.1. Within the critical region of
      the PSORS9 locus, IL-15 has been long recognized as a strong candidate gene for
      psoriasis. In this study, we investigated the association between IL-15 genetic
      polymorphisms and psoriasis in a large Chinese sample. Highly significant
      evidence for association was identified at a single-nucleotide polymorphism (SNP)
      (g.96516A --> T) within the 3'-untranslated region (UTR) of the IL-15 gene
      (P=0.00006, after correction for multiple testing). Haplotype analysis using the
      SNPs within the 3'UTR region also provided strong supporting evidence for
      association (P=0.00005), where we identified a haplotype of the 3'UTR region of
      IL-15 associated with increased risk to psoriasis (odds ratio=1.65). This
      association was also supported by the results of our expression activity
      analyses, where we demonstrated that the identified risk haplotype is associated
      with an increased activity of IL-15. Therefore, we provided early evidence for
      the important role of IL-15 genetic variants in the pathogenesis of psoriasis,
      probably by increasing interleukin production and inflammation in the lesions of
      psoriasis.

PMID- 17554369
TI  - TNF-alpha suppresses alpha-smooth muscle actin expression in human dermal
      fibroblasts: an implication for abnormal wound healing.
AB  - Abnormal wound healing encompasses a wide spectrum, from chronic wounds to
      hypertrophic scars. Both conditions are associated with an abnormal cytokine
      profile in the wound bed. In this study, we sought to understand the dynamic
      relationships between myofibroblast differentiation and mechanical performance of
      the collagen matrix under tissue growth factor-beta (TGF-beta) and tumor necrosis
      factor-alpha (TNF-alpha) stimulation. We found TGF-beta increased alpha-smooth
      muscle actin (alpha-SMA) and TNF-alpha alone decreased the basal alpha-SMA
      expression. When TGF-beta1 and TNF-alpha were both added, the alpha-SMA
      expression was suppressed below the baseline. Real-time PCR showed that TNF-alpha
      suppresses TGF-beta1-induced myofibroblast (fibroproliferative) phenotypic genes,
      for example, alpha-SMA, collagen type 1A, and fibronectin at the mRNA level. TNF
      alpha suppresses TGF-beta1-induced gene expression by affecting its mRNA
      stability. Our results further showed that TNF-alpha inhibits TGF-beta1-induced
      Smad-3 phosphorylation via Jun N-terminal kinase signaling. Mechanical testing
      showed that TNF-alpha decreases the stiffness and contraction of the lattices
      after 5 days in culture. We proposed that changes in alpha-SMA, collagen, and
      fibronectin expression result in decreased contraction and stiffness of collagen
      matrices. Therefore, the balance of cytokines in a wound defines the mechanical
      properties of the extracellular matrix and optimal wound healing.

PMID- 17554370
TI  - Single base instability is promoted in vulvar lichen sclerosus.
AB  - Single base substitution mutations in codons 248 and 273 of TP53 and codon 12
      Kirsten-ras (KRAS) are commonly found in human carcinomas. To determine whether
      these mutations also occur in normal and inflamed tissues from which carcinomas
      arise, we utilized the ultra-sensitive polymerase chain reaction/restriction
      endonuclease/ligase chain reaction mutation assay. Ninety samples of genital
      skin, including lichen sclerosus (LS) affected skin, adjacent normal and non
      adjacent normal, were assayed. Mutations were detected in 103 of 349 assays and
      consisted of KRAS G34A, G34T, G35A, and TP53 C742T, G818C, C817T, and G818A
      mutations. Mutant prevalence varied from 1 to 20 per 10(6) wild-type cells.
      Mutations occurred significantly more frequently in LS (78/224 (35%)) than
      adjacent normal (20/88 (23%)) and non-adjacent normal genital skin (5/38 (13%)).
      KRAS G34A mutation was relatively common to all classes of specimen, whereas TP53
      gene C742T and G818C mutations were significantly more frequent in LS than normal
      genital skin. In matched samples, immunohistochemistry evaluation of p53 protein
      expression revealed the presence of epidermal p53 clones in LS whose presence and
      number significantly correlated with the presence of TP53 C742T and G818C
      mutations. Based on these results, it appears oncogenic point mutations occur in
      normal genital skin, and are selected for in LS.

PMID- 17554371
TI  - Diagnosing Treponema pallidum in secondary syphilis by PCR and
      immunohistochemistry.
AB  - Epidemiological aspects of syphilis in Western countries have undergone a
      significant change with respect to the number of cases. Detection of Treponema
      pallidum is difficult, and the correct diagnosis of secondary syphilis can be
      critical. In this study, biopsy samples from skin lesions of 12 patients with
      secondary syphilis were used. Diagnosis of syphilis was based on clinical
      presentation, dark-field microscope analysis, and serological tests. Using a
      polyclonal antibody directed against T. pallidum, we show the presence of T.
      pallidum in 90% of the samples studied with the bacteria located in the epidermis
      and the upper dermis. The T. pallidum 47-kDa surface protein gene could be
      amplified by PCR in 75% of the skin lesions. When combining both techniques, T.
      pallidum was detected in 92% of the samples from patients with secondary syphilis
      but not in the control samples. Our work suggests that both immunohistochemistry
      and PCR could be useful for the diagnosis of secondary syphilis and may be
      helpful in some rare cases when serological assays failed to detect T. pallidum
      antibodies.

PMID- 17554372
TI  - Splenectomy status of the patient may have impact on response to donor lymphocyte
      infusions.

PMID- 17554374
TI  - Segmental uniparental disomy as a recurrent mechanism for homozygous CEBPA
      mutations in acute myeloid leukemia.

PMID- 17554373
TI  - Transcriptional regulation of parathyroid hormone-related protein promoter P2 by
      NF-kappaB in adult T-cell leukemia/lymphoma.
AB  - Parathyroid hormone-related protein (PTHrP) plays a primary role in the
      development of humoral hypercalcemia of malignancy (HHM) that occurs in the
      majority of patients with adult T-cell leukemia/lymphoma (ATLL) due to human T
      cell lymphotropic virus type-1 (HTLV-1) infection. We previously showed that ATLL
      cells constitutively express high levels of PTHrP via activation of promoters P2
      and P3, resulting in HHM. In this study, we characterized a nuclear factor-kappaB
      (NF-kappaB) binding site in the P2 promoter of human PTHrP. Using electrophoretic
      mobility shift assays, we detected a specific complex in Tax-expressing human T
      cells composed of p50/c-Rel, and two distinct complexes in ATLL cells consisting
      of p50/p50 homodimers and a second unidentified protein(s). Chromatin
      immunoprecipitation assays confirmed in vivo binding of p50 and c-Rel on the
      PTHrP P2 promoter. Using transient co-transfection with NF-kappaB expression
      plasmids and PTHrP P2 luciferase reporter-plasmid, we showed that NF-kappaB
      p50/p50 alone and p50/c-Rel or p50/Bcl-3 cooperatively upregulated the PTHrP P2
      promoter. Furthermore, inhibition of NF-kappaB activity by Bay 11-7082 reduced
      PTHrP P2 promoter-initiated transcripts in HTLV-1-infected T cells. In summary,
      the data demonstrated that transcriptional regulation of PTHrP in ATLL cells can
      be controlled by NF-kappaB activation and also suggest a Tax-independent
      mechanism of activation of PTHrP in ATLL.

PMID- 17554375
TI  - Influence of two different regimens of concomitant treatment with asparaginase
      and dexamethasone on hemostasis in childhood acute lymphoblastic leukemia.

PMID- 17554376
TI  - Successful treatment of imatinib-resistant acute megakaryoblastic leukemia with
      e6a2 BCR/ABL: use of dasatinib and reduced-conditioning stem-cell
      transplantation.

PMID- 17554377
TI  - Impairment of Na(+),K(+)-ATPase in CD95(APO-1)-induced human T-cell leukemia cell
      apoptosis mediated by glutathione depletion and generation of hydrogen peroxide.
AB  - Human T-cell leukemia is a malignant disease that needs various regimens of
      cytotoxic chemotherapy to overcome drug resistance. Recently, Na(+),K(+)-ATPase
      has emerged as a potential target for cancer therapy. However, its exact
      signaling pathway in human T-cell leukemia cell death has not been well defined.
      In the current study, we found CD95(APO-1) was able to trigger the
      internalization of plasma membrane Na(+),K(+)-ATPase in Jurkat cells or primary T
      cells as a mechanism to suppress its activity. This internalization was closely
      relevant to intracellular glutathione (GSH) depletion in Jurkat cells downstream
      of Fas-associated death domain protein (FADD) and caspase 8. GSH depletion in Fas
      L-treated Jurkat cells induced the generation of hydrogen peroxide (H(2)O(2)),
      which subsequently increased the serine phosphorylation of Na(+),K(+)-ATPase
      alpha1 subunit. Exogenous H(2)O(2) even mimicked the effect of Fas L to
      upregulate the serine phosphorylation of Na(+),K(+)-ATPase alpha1 subunit and
      suppress Na(+),K(+)-ATPase activity. Overall, our results indicate that CD95(APO
      1) induces the FADD- and caspase 8-dependent internalization of Na(+),K(+)-ATPase
      through intracellular GSH loss, and the subsequent generation of H(2)O(2)
      mediated serine phosphorylation of Na(+),K(+)-ATPase alpha1 subunit. Taken
      together, this study presents a novel regulatory mechanism of Na(+),K(+)-ATPase
      in CD95(APO-1)-mediated human T-leukemia cell apoptosis.

PMID- 17554378
TI  - Induction of folate receptor type beta in a bone marrow engraftment model of
      acute myelogenous leukemia.

PMID- 17554379
TI  - Adult ALL: treatment outcome and prognostic factors in an Indian population using
      a modified German ALL (GMALL) protocol.

PMID- 17554380
TI  - Upregulation of the SOX5 by promoter swapping with the P2RY8 gene in primary
      splenic follicular lymphoma.

PMID- 17554381
TI  - MALT lymphoma in patients with autoimmune diseases: a comparative analysis of
      characteristics and clinical course.
AB  - MALT lymphoma, especially of extragastric origin, is thought to be associated
      with an underlying autoimmune disease (AD) in a significant proportion of
      patients. No systematic assessment of the clinical characteristics of MALT
      lymphoma arising in AD as opposed to patients without AD has been performed so
      far. Therefore, all patients diagnosed and treated for MALT lymphoma at our
      institution have prospectively undergone routine clinical and serological
      assessment for AD since 1997. In total, 158 patients were available for analysis,
      and 61 out of 158 patients (39%) were diagnosed with an underlying AD. Patients
      with AD were predominantly women and significantly younger at lymphoma diagnosis
      (56 versus 67 years, P=0.004), with a significantly higher rate of extragastric
      lymphomas (P=0.012). Furthermore, lymphomas in these patients showed a lower
      frequency of trisomy 3 (P=0.04) and a significantly lower response rate to
      Helicobacter pylori eradication therapy in the case of gastric lymphomas
      (P=0.03). All other parameters including estimated median time to relapse were
      comparable between both groups. Our data suggest that patients with AD develop
      MALT lymphoma significantly earlier in life. The clinical course, however, does
      not appear to be adversely influenced by the presence of AD, as neither rate of
      relapse nor times to relapse or survival are significantly different.

PMID- 17554382
TI  - Prolonged survival in poor-risk diffuse large B-cell lymphoma following front
      line treatment with rituximab-supplemented, early-intensified chemotherapy with
      multiple autologous hematopoietic stem cell support: a multicenter study by GITIL
      (Gruppo Italiano Terapie Innovative nei Linfomi).
AB  - A prospective multicenter program was performed to evaluate the combination of
      rituximab and high-dose (hd) sequential chemotherapy delivered with multiple
      autologous peripheral blood progenitor cell (PBPC) support (R-HDS-maps regimen)
      in previously untreated patients with diffuse large B-cell lymphoma (DLB-CL) and
      age-adjusted International Prognostic Score (aaIPI) score 2-3. R-HDS-maps
      includes: (i) three APO courses; (ii) sequential administration of hd
      cyclophosphamide (CY), hd-Ara-C, both supplemented with rituximab, hd
      etoposide/cisplatin, PBPC harvests, following hd-CY and hd-Ara-C; (iii) hd
      mitoxantrone (hd-Mito)/L-Pam + 2 further rituximab doses; (iv) involved-field
      radiotherapy. PBPC rescue was scheduled following Ara-C, etoposide/cisplatin and
      Mito/L-Pam. Between 1999 and 2004, 112 consecutive patients aged <65 years (74
      score 2, 38 score 3) entered the study protocol. There were five early and two
      late toxic deaths. Overall 90 patients (80%) reached clinical remission (CR); at
      a median 48 months follow-up, 87 (78%) patients are alive, 82 (73%) in continuous
      CR, with 4 year overall survival (OS) and event-free survival (EFS) projections
      of 76% (CI 68-85%) and 73% (CI 64-81%), respectively. There were no significant
      differences in OS and EFS between subgroups with Germinal-Center and Activated B
      cell phenotype. Thus, life expectancy of younger patients with aaIPI 2-3 DLB-CL
      is improved with the early administration of rituximab-supplemented intensive
      chemotherapy compared with the poor outcome following conventional chemotherapy.

PMID- 17554383
TI  - Absolute lymphocyte counts predicts response to chemotherapy and survival in
      diffuse large B-cell lymphoma.

PMID- 17554384
TI  - BH3 mimetic ABT-737 neutralizes resistance to FLT3 inhibitor treatment mediated
      by FLT3-independent expression of BCL2 in primary AML blasts.
AB  - FLT3 defines a promising target for the treatment of acute myeloid leukemia
      (AML). In contrast to their efficacy in cell lines, FLT3-specific inhibitors as
      single agents have only modest clinical activity in patients with AML. As
      demonstrated here, overexpression of anti-apoptotic proteins of the BCL2 family
      leads to resistance against FLT3 inhibitors in a hematopoietic cell line model
      with activating FLT3 mutations. The susceptibility to FLT3 inhibition could be
      restored by treatment with the novel BH3 mimetic ABT-737. Primary AML samples
      tested in our study showed a high expression of BCL2 protein, but not of BCL-xL
      or MCL1. BCL2 protein levels were not reduced after dephosphorylation of FLT3 and
      its downstream target STAT5 in patient samples with FLT3 internal tandem
      duplications. Interestingly, treatment with ABT-737 caused apoptotic cell death
      in all primary AML samples at submicromolar level and synergized efficiently with
      FLT3 inhibition in AML samples with activating FLT3 mutations. In contrast to AML
      cell lines, BCR-ABL transformed human cells showed resistance to ABT-737, which
      might be due to the induction of MCL1 by BCR-ABL. Inhibition of BCL2 family
      members might define a novel highly efficient and specific strategy in the
      combined or monotreatment of AML.

PMID- 17554385
TI  - The rho-kinase inhibitors Y-27632 and fasudil act synergistically with imatinib
      to inhibit the expansion of ex vivo CD34(+) CML progenitor cells.
AB  - Evidence from cell line-based studies indicates that rho-kinase may play a role
      in the leukaemic transformation of human cells mediated by the BCR/ABL tyrosine
      kinase, manifest clinically as chronic myeloid leukaemia (CML). We therefore
      employed two separate inhibitors, Y-27632 and fasudil, to inhibit the activity of
      rho-kinase against ex vivo CD34(+) cells collected from patients with CML. We
      compared the effects of rho-kinase inhibition in those cells with the effects of
      direct inhibition of BCR/ABL using the specific inhibitor imatinib. We found that
      inhibition of rho-kinase inhibited the effective proliferation, and reduced
      survival of CML progenitor cells. When combined with imatinib, rho-kinase
      inhibition added to the anti-proliferative and pro-apoptotic effects of the
      BCR/ABL inhibitor. Our studies may indicate therapeutic benefit in some cases for
      the combination of rho-kinase inhibitors with imatinib.

PMID- 17554386
TI  - Clonality of the stem cell compartment during evolution of myelodysplastic
      syndromes and other bone marrow failure syndromes.
AB  - Clonal hematopoiesis, observed in certain forms of marrow failure including
      aplastic anemia (AA), may be due to stem cell depletion. Alternatively,
      oligoclonality may be a result of recruitment of a preexisting defective clone,
      such as in paroxysmal nocturnal hemoglobinuria (PNH) or myelodysplastic syndromes
      (MDS). In PNH, exogenous permissive factors may be required for dominance of the
      abnormal clone, while in MDS, stem cells undergo transformation steps leading to
      a growth advantage. Stem or multipotent progenitor cell involvement in PNH is
      evidenced by long-term persistence of a clonal defect and its presence in all
      blood cells. In MDS, some clonal aberrations may have a 'founder-effect' and
      additional defects are secondary. Metaphase cytogenetics measures the proportion
      of clonal cells within dividing progenitor but not mature cells. Owing to low
      resolution, lesions can be found in only approximately 50% of MDS patients. This
      shortcoming may be overcome by application of newer technologies such as
      comparative genomic hybridization and SNP array-based karyotyping (SNP-A). SNP-A
      facilitates identification of cryptic lesions in bone marrow failure patients
      with normal or abnormal cytogenetics and allows for detection of loss of
      heterozygosity as a result of uniparental disomy, a lesion frequently found in
      MDS.

PMID- 17554387
TI  - The emerging role of Wnt signaling in the pathogenesis of acute myeloid leukemia.
AB  - Wnt signaling plays an important role in stem cell self-renewal and
      proliferation. Aberrant activation of Wnt signaling and its downstream targets
      are intimately linked with several types of cancer with colon cancer being the
      best-studied example. However, recent results also suggest an important role of
      Wnt signaling in normal as well as leukemic hematopoietic stem cells. Aberrant
      activation of Wnt signaling and downstream effectors has been demonstrated in
      acute myeloid leukemia. Here, mutant receptor tyrosine kinases, such as Flt3 and
      chimeric transcription factors such as promyelocytic leukemia-retinoic acid
      receptor-alpha and acute myeloid leukemia1-ETO, induce downstream Wnt signaling
      events. These findings suggest that the Wnt signaling pathway is an important
      target in several leukemogenic pathways and may provide a novel opportunity for
      targeting leukemic stem cells.

PMID- 17554388
TI  - Molecular detection of GNNK- and GNNK+ c-kit isoforms: a new tool for risk
      stratification in adult acute myeloid leukaemia.

PMID- 17554390
TI  - Maternal and cord serum lipid profiles of preterm infants with respiratory
      distress syndrome.
AB  - BACKGROUND: Lipid metabolism has an important role in fetal development during
      the late stage of gestation, including growth and fat accretion in utero,
      increasing amniotic fluid lecithin levels with maturation of pulmonary function
      and changes in the levels of minor phospholipids in amniotic fluid. OBJECTIVE:
      The aim of this study was to compare the maternal and cord lipid profiles of
      preterm infants with respiratory distress syndrome (RDS) and a control group
      without RDS. METHOD: The study groups consisted of 166 preterm infants with
      gestational ages ranging from 25 to 36 weeks, and birth weights ranging from 748
      to 2495 g. Of these infants, 57 developed RDS and 109 infants served as controls.
      The infants were divided into four gestational age groups (34 to 36, 31 to 33, 28
      to 30 and 25 to 27 weeks). Stepwise linear regression analyses were performed to
      determine independent contribution of each lipid parameter of the infants to
      their characteristics and mothers' variables. RESULT: Total cholesterol, high
      density and low-density lipoproteins (LDL) cholesterols levels were lower in
      infants with RDS and in their mothers than in controls, and maternal lipid
      profile was related to those of their infants (P<0.05). Pregravid body mass index
      (BMI) was related to triglyceride levels of the infants, and weight gain during
      pregnancy was related to LDL cholesterol levels of the infants (P<0.05).
      CONCLUSION: RDS is accompanied with lipid alteration in infants and their
      mothers. Pregravid BMI and weight gain during pregnancy might have a prognostic
      significance in the prediction of respiratory distress in early neonatal period.

PMID- 17554391
TI  - The use of fat-free human milk in infants with chylous pleural effusion.
AB  - OBJECTIVE: The purpose of this study is to describe the processing of human milk
      to remove its fat content and its use in seven infants with chylothorax. STUDY
      DESIGN: The mother's milk was centrifuged at 3000 r.p.m. for 15 min at 2 degrees
      C. After centrifugation, the milk separated into a solidified-fat top layer and a
      lower liquid portion. The fat-free liquid portion was then poured into collection
      cups and frozen for the patient's use at a later date. A sample of the mother's
      milk before and after processing was stored and analyzed for fat, sodium,
      potassium, calcium and zinc. RESULTS: The mean fat removed was 5+/-1 g/dl (mean+/
      s.d.), which was the same as the pre-fat content of the mother's milk. Seven
      infants with chylous pleural effusions used the fat-free human milk. All infants
      started on the fat-free milk after a month of age for an average of 16 days
      duration (7 to 34 days range). There was no reaccumulation of the chylous pleural
      effusions with the use of the fat-free mother's milk. Mother's milk electrolytes
      were similar before and after processing. CONCLUSION: Fat-free human milk may be
      an important additional dietary therapy for infants with chylothorax and may add
      the immunologic properties of human milk that other feedings cannot provide.

PMID- 17554392
TI  - Ethnic differences in risk factors for neonatal mortality and morbidity in the
      neonatal intensive care unit.
AB  - OBJECTIVE: Although our knowledge about how to care for high-risk neonates who
      require intensive care is continually improving, disparities in health outcomes
      among various ethnic groups living in developed countries are becoming more
      evident. The purpose of this study was to identify the risk factors for neonatal
      intensive care unit (NICU) mortality among Canadian-born minority infants and,
      furthermore, to determine whether ethnicity was in itself an independent
      predictor of mortality or major morbidity in the NICU. STUDY DESIGN: Data were
      prospectively gathered on 6528 infants admitted to nine regionally located NICUs
      across Canada. Multiple logistic regressions were used to develop risk-adjusted
      models for NICU mortality and major morbidity. RESULT: Despite adjusting for
      differences in small for gestational age (SGA), outborn status and gestational
      age less than or equal to 28 weeks, South Asian infants still had significantly
      greater odds of mortality in the NICU. Neonatal sepsis was the strongest
      predictor of mortality among African infants, even greater than birth at 28 weeks
      or less. At significantly greater odds of survival with major morbidity were
      Aboriginal males and East Asian females. CONCLUSION: There are ethnic disparities
      in the risks of neonatal mortality and morbidity in the NICU. Understanding these
      differences is important to be able to determine specific areas to target in
      improving healthcare delivery and reducing disparities in health outcomes among
      Canada's diverse population.

PMID- 17554393
TI  - False penile fracture: report of 16 cases.
AB  - We determined the value of diagnostic and therapeutic approaches of false penile
      fractures and the outcome of treatment. We retrospectively reviewed 16 cases of
      presumed penile fracture with a negative surgical exploration. Clinical
      presentation, technique of treatment and outcome were noted. The mean age was 39
      years (17-64). Nine patients were injured during sexual intercourse. All the
      patients presented with the presumptive diagnosis of penile fracture. False
      penile fracture was evoked in one patient presenting a new erection. Surgical
      penile exploration was carried out for all the patients without any radiological
      explorations. It revealed nonspecific dartos bleeding in 10 cases and avulsed
      superficial dorsal vein in six cases requiring venous ends ligation. All the
      patients regained penile appearance and potency. We can hardly distinguish false
      penile fracture from 'true' penile fracture with certainty either clinically or
      radiologically, thus, surgical exploration is mostly necessary. The prognosis is
      excellent.

PMID- 17554394
TI  - Paraoxonase activity in patients with erectile dysfunction.
AB  - Paraoxonase (PON1) is a high-density lipoprotein (HDL)-associated enzyme that
      protects low-density lipoprotein (LDL) and HDL from peroxidation. In this study,
      PON1 activities were determined in patients with erectile dysfunction (ED) to
      investigate the relationship between ED and atherosclerosis. Forty patients, who
      had been diagnosed with ED by the medical and sexual anamnesis and routine
      laboratory tests, were included in the study. Thirty healthy, sexually active,
      married and age-matched men were selected as the control group. The patients and
      controls who underwent surgical or medical treatment in 1-week time and had a
      systemic disease such as malignancy, liver and renal insufficiency, and active
      infection and who smoked cigarettes were excluded. PON1 activities were measured
      spectrophotometrically. Unpaired samples t-test, correlation analyses and
      multiple linear regression analyses were used for statistical analyses. The
      results are given as mean+/-standard deviation of mean. The mean ages of the
      patient and the control groups were 31.05+/-6.90 (range 22-51) and 29.40+/-6.26
      (range 19-46), respectively (P=0.307). Serum PON1 levels of the patient and the
      control groups were found to be 119.05+/-62.11 and 185.04+/-55.64, respectively.
      The difference between the groups was quite significant (P=0.001).
      Epidemiological and experimental studies indicate that PON1 activation was lower
      in individuals who had a tendency to develop atherosclerosis due to comorbidities
      such as diabetes, familial hypercholesterolemia and kidney disease. In this
      study, PON1 activity level was found to be significantly lower in ED patients
      than in control group. The decrease of PON1 activity may have a role in the
      ethiopathogenesis of ED, and the atherosclerosis development may be faster in the
      patients due to decreased activity of PON1, which is an antiatherogenic enzyme.

PMID- 17554395
TI  - Correlation between lower urinary tract symptoms and erectile dysfunction in men
      presenting for prostate cancer screening.
AB  - Lower urinary tract symptoms (LUTS) and erectile dysfunction (ED) are age-related
      conditions that may have a profound impact on the quality of life. The
      relationship between LUTS and ED is not completely understood. In this study, we
      assessed this relationship in men over 45 years of age during a prostate cancer
      screening program. LUTS and ED were evaluated in 1267 men aged 45-75 years (mean
      58.2+/-8.2 years). Patients completed the International Prostate Symptom Score
      (IPSS) and the International Index of Erectile Function-5 (IIEF-5). The
      association between LUTS and ED was analyzed and the influence of age in the
      results was tested. We also evaluated the influence of the intensity of LUTS in
      the ED severity. A total of 514 (40.6%) patients were considered symptomatic of
      LUTS (24.8% with mild, 11.8% with moderate and 4% with severe LUTS). ED was
      present in 758 (59.9%) men and was considered mild in 25.0%, moderate in 18.3%
      and severe in 16.7%. The IIEF-5 score had a negative correlation with both the
      IPSS score (r=-0.33, P<0.001) and age (r=-0.31 and P<0.001). Age was positively
      associated with the IPSS score (r=0.14 and P<0.001). A significant correlation
      was observed between LUTS and ED, with 57.6% of the men with LUTS presenting ED
      as opposed to 29.7% of the asymptomatic population (odds ratio=3.32; 95% CI =2.57
      4.29, P<0.001). Age-adjusted univariate analysis revealed a significant and
      independent influence of LUTS on the incidence of ED (odds ratio=2.72; 95%
      CI=2.08-3.57, P<0.001). IIEF scores varied significantly according to the
      severity of the urinary symptoms. Our findings in a prostate cancer screening
      population confirm that LUTS is an age-independent predictor of ED. Furthermore,
      they demonstrate that not only the presence of LUTS increases the likelihood of
      developing ED, but the severity of LUTS is associated with the intensity of ED.

PMID- 17554396
TI  - Body composition, metabolic syndrome and testosterone in ageing men.
AB  - The ageing process in men is marked by changes in body composition (loss of fat
      free mass (FFM) and skeletal muscle, and gain in fat mass (FM)) and is associated
      with a decline in serum testosterone. Correlations between these aspects of
      ageing and the acknowledged role of exogenous testosterone in reversing the loss
      of FFM and gain in FM seen in adult men with congenital or acquired
      hypoandrogenism have led to the hypothesis that testosterone therapy in ageing
      men will result in favourable changes in body composition and may improve
      metabolic status and/or cardiovascular risk. Data from randomized controlled
      trials of testosterone therapy in ageing men addressing the endpoints of body
      composition and components of the metabolic syndrome and cardiovascular risk
      factors are reviewed, and the impact of the increasing prevalence of obesity on
      these relationships is considered.

PMID- 17554397
TI  - Toxicology and carcinogenesis studies of diisopropylcarbodiimide (Cas No. 693-13
      0) in F344/N rats and B6C3F1 mice (dermal studies).
AB  - Diisopropylcarbodiimide is used as a reagent for peptide syntheses and as a
      chemical intermediate. The National Cancer Institute nominated
      diisopropylcarbodiimide for study as a representative chemical in the
      alkylcarbodiimide class because of its acute toxicity; its use in chemical,
      pharmaceutical, and recombinant DNA industries; and the absence of data on
      potential health effects. Male and female F344/N rats and B6C3F1 mice were
      administered diisopropylcarbodiimide (greater than 99% pure) dermally for 2
      weeks, 3 months, or 2 years. Genetic toxicology studies were conducted in
      Salmonella typhimurium, rat and mouse bone marrow cells, and mouse peripheral
      blood erythrocytes. 2-WEEK STUDY IN RATS: Groups of five male and five female
      F344/N rats were dermally administered 0.3 mL ethanol containing 0, 3, 9, 27, or
      81 mg diisopropylcarbodiimide or 0.3 mL of the neat chemical containing 242 mg
      per animal, 5 days a week for 2 weeks. All rats in the 27, 81, and 242 mg groups
      died before the end of the study. Of the surviving groups, final body weights
      were similar to those of the vehicle controls. Clinical findings included
      convulsions/seizures, nasal/eye discharge, tremors, and comatose conditions in 81
      and 242 mg rats and lethargy, ataxia, and abnormal breathing in 27 mg rats. The
      incidences of epidermal hyperplasia at the site of application in 9 and 27 mg
      males and 27 mg females were significantly greater than those in the vehicle
      controls; the incidences of hyperkeratosis in 3 and 9 mg males and 9 mg females
      were also significantly increased. 2-WEEK STUDY IN MICE: Groups of five male and
      five female B6C3F1 mice were dermally administered 0.1 mL ethanol containing 0,
      1, 3, 9, or 27 mg diisopropylcarbodiimide or 0.1 mL of the neat chemical
      containing 81 mg per animal, 5 days a week for 2 weeks. All 9, 27, and 81 mg mice
      died before the end of the study. Final body weights of the surviving groups were
      similar to those of the vehicle controls. Clinical findings in 9, 27, and 81 mg
      mice included comatose conditions, convulsions/seizures, tremors, abnormal
      breathing, nasal/eye discharge, lethargy, and irritation at the site of
      application. Incidences of chronic active inflammation at the site of application
      in 9 mg males and females were significantly greater than those in the vehicle
      control groups. 3-MONTH STUDY IN RATS: Groups of 10 male and 10 female core study
      F344/N rats were dermally administered 0, 10, 20, 40, 80, or 160 mg
      diisopropylcarbodiimide/kg body weight in ethanol, 5 days per week for 3 months.
      Groups of 10 male and 10 female clinical pathology rats were administered the
      same doses for 22 days. All 160 mg/kg core study rats were sacrificed moribund or
      died within the first week of the study. All 80 mg/kg rats died or were found
      moribund by day 59. Significant decreases in body weight gain occurred in 40
      mg/kg males and females, and a significant decrease in final mean body weight
      occurred in 40 mg/kg females. Clinical findings in groups administered 40 mg/kg
      or more generally included irritation of the skin at the site of application,
      seizures, ataxia, abnormal breathing, ruffled fur, thinness, and lethargy.
      Significantly increased incidences of skin lesions at the site of application
      included epidermal hyperplasia in all dosed groups of males (except 160 mg/kg)
      and 40 mg/kg or greater females, epidermal necrosis in 160 mg/kg males and
      females, and chronic active inflammation in 80 and 160 mg/kg males and females.
      Significantly increased incidences of nonneoplastic lesions occurred in the
      brain, lung, and liver (males only) of rats administered 80 or 160 mg/kg. 3-MONTH
      STUDY IN MICE Groups of 10 male and 10 female B6C3F1 mice were dermally
      administered 0, 17.5, 35, 70, 140, or 280 mg/kg diisopropylcarbodiimide in
      ethanol, 5 days per week for 3 months. All mice in the 280 mg/kg group and nine
      males and nine females in the 140 mg/kg group died before the end of the study.
      The final mean body weight gain of 70 mg/kg males was significantly less than
      that of the vehicle control group. Clinical findings observed in 140 and 280
      mg/kg mice included abnormal breathing, ataxia, comatose conditions,
      convulsions/seizures, irritation at the site of application, lethargy, ruffled
      fur, and thinness. Significant increases in kidney weights occurred in 17.5 and
      35 mg/kg males. Significant decreases in total spermatid heads per testis and
      average spermatid count occurred in 17.5 mg/kg males. At the site of application,
      the incidences of epidermal hyperplasia in males and females administered 70
      mg/kg or greater, chronic inflammation in 140 and 280 mg/kg males and 70 mg/kg or
      greater females, and sebaceous gland hyperplasia in 140 mg/kg males were
      significantly increased. Thymic atrophy was significantly increased in 140 and
      280 mg/kg males and females. 2-YEAR STUDY IN RATS: Groups of 50 male and 50
      female F344/N rats were dermally administered 0, 10, 20, or 40 mg/kg
      diisopropylcarbodiimide in anhydrous ethanol 5 days per week for 2 years.
      Survival of 20 mg/kg males was significantly greater than that of the vehicle
      controls; survival of all dosed groups of females was similar to that of the
      vehicle controls. Body weights of 40 mg/kg rats were generally less than those of
      the vehicle controls after week 13. Clinical findings frequently observed in 40
      mg/kg males included ataxia, excitability, impaired gait, low muscle tone,
      abnormal breathing, lethargy, vocalization, and seizures. Because of severe
      neurological signs exhibited by the 40 mg/kg males, a neuropathological review of
      these animals was performed. The principal pathological findings of the brain
      included neuronal necrosis, hemorrhage, and/or fibrinoid arteriole necrosis.
      Incidences of hemorrhage in the lung of 40 mg/kg males, chronic lung inflammation
      in 10 and 20 mg/kg females, and alveolar epithelium hyperplasia in 20 mg/kg
      females were significantly greater than those of the vehicle controls. At the
      site of application, the incidences of epidermal hyperplasia in all dosed groups
      of males and 20 and 40 mg/kg females and chronic inflammation in all dosed groups
      of males and 40 mg/kg females were significantly increased. There was no
      increased incidences of neoplasms related to diisopropylcarbodiimide
      administration. 2-YEAR STUDY IN MICE: Groups of 50 male and 50 female B6C3F1 mice
      were dermally administered 0, 10, 20, or 40 mg/kg diisopropylcarbodiimide in
      anhydrous ethanol, 5 days per week for 2 years. Survival of all dosed groups was
      similar to that of the vehicle control groups. Mean body weights of dosed groups
      of mice were generally similar to those of the vehicle control groups throughout
      the study. There were no increased incidences of neoplasms that were attributed
      to the administration of diisopropylcarbodiimide. Significantly increased
      incidences of epidermal hyperplasia and focal dermal inflammation of the skin at
      the site of application occurred in 20 mg/kg male mice. GENETIC TOXICOLOGY:
      Diisopropylcarbodiimide was not mutagenic in Salmonella typhimurium strains TA97,
      TA98, TA100, or TA1535 with or without liver S9 activation enzymes. In vivo, the
      frequency of micronucleated normochromatic erythrocytes was significantly
      increased in male and female mice after 3 months of dermal exposure to
      diisopropylcarbodiimide. In addition, significantly elevated frequencies of
      micronucleated polychromatic erythrocytes (reticulocytes) and micronucleated
      normochromatic erythrocytes were seen in male mice during a 4-month dermal
      exposure to diisopropylcarbodiimide. Negative results were obtained, however, in
      an acute three-injection rat bone marrow micronucleus study. A three-treatment
      acute micronucleus test in male mice also showed no increase in micronucleated
      erythrocytes, but results of a single injection micronucleus test in male mice
      were concluded to be equivocal, due to an increase in micronucleated erythrocytes
      seen in peripheral blood but not in bone marrow preparations. CONCLUSIONS: Under
      the conditions of these 2-year dermal studies, there was no evidence of
      carcinogenic activity of diisopropylcarbodiimide in male or female F344/N rats or
      B6C3F1 mice administered 10, 20, or 40 mg/kg. Clinical and histological signs of
      neurotoxicity in male rats were associated with diisopropylcarbodiimide
      administration.

PMID- 17554398
TI  - Toxicology and carcinogenesis studies of dibromoacetic acid (Cas No. 631-64-1) in
      F344/N rats and B6C3F1 mice (drinking water studies).
AB  - Dibromoacetic acid is a water disinfection by-product. Dibromoacetic acid was
      nominated to the National Toxicology Program by the United States Environmental
      Protection Agency for toxicity and carcinogenicity studies in rats and mice
      because of widespread human exposure and because a related dihaloacetate,
      dichloroacetate, was found to be carcinogenic to the liver of rats and mice.
      Drinking water was selected as the route of exposure to mimic human exposure to
      this chemical. Male and female F344/N rats and B6C3F1 mice were exposed to
      dibromoacetic acid (greater than 99% pure) in drinking water for 2 weeks, 3
      months, or 2 years. Genetic toxicology studies were conducted in Salmonella
      typhimurium and peripheral blood erythrocytes of exposed mice. 2-WEEK STUDY IN
      RATS: Groups of five male and five female rats were exposed to 0, 125, 250, 500,
      1,000, or 2,000 mg/L dibromoacetic acid in drinking water for 2 weeks, equivalent
      to average daily doses of approximately 17, 32, 67, 134, 270 (males), or 257
      (females) mg dibromoacetic acid/kg body weight. All rats survived to the end of
      the study. Mean body weight gains of 1,000 mg/L males and of 500 mg/L females
      were significantly greater than those of the controls. Water consumption by
      exposed and control groups was similar. Liver weights of exposed males and
      females were significantly increased. Right testis weights of males exposed to
      500 mg/L or greater were significantly decreased. The incidences of hepatocytic
      cytoplasmic alteration were significantly increased in males exposed to 500 mg/L
      or greater and in 2,000 mg/L females. Testicular lesions, characterized by a
      delay in spermiation and retained spermatids, were noted in males exposed to 500
      mg/L or higher concentrations. 2-WEEK STUDY IN MICE: Groups of five male and five
      female mice were exposed to 0, 125, 250, 500, 1,000, or 2,000 mg/L dibromoacetic
      acid (equivalent to average daily doses of approximately 24, 47, 95, 178, or 370
      mg/kg to males and 22, 53, 88, 166, or 309 mg/kg to females) in drinking water
      for 2 weeks. All mice survived to the end of the study. Mean body weight gains of
      250 and 500 mg/L males were significantly greater than those of the controls.
      Water consumption by exposed and control groups was similar. Liver weights of
      males and females in the 1,000 and 2,000 mg/L groups were significantly
      increased. Thymus weights of males and females in the 1,000 and 2,000 mg/L groups
      were significantly less than those of controls. The incidences of thymus atrophy
      were significantly increased in 1,000 and 2,000 mg/L males and 2,000 mg/L
      females. The incidences of morphological changes to the germinal epithelium of
      the testes were increased in males exposed to 1,000 or 2,000 mg/L. 3-MONTH STUDY
      IN RATS: Groups of 10 male and 10 female rats were exposed to 0, 125, 250, 500,
      1,000, or 2,000 mg/L dibromoacetic acid (equivalent to average daily doses of
      approximately 10, 20, 40, 90, and 166 mg/kg to males and 12, 23, 48, 93, and 181
      mg/kg to females) in drinking water for 3 months. All rats survived to the end of
      the study. Mean body weights of male and female rats in the 2,000 mg/L group were
      significantly less than those of controls. Water consumption by the 2,000 mg/L
      males at weeks 1 and 13 and by females at week 13 was less than that by controls.
      Small decreases in the erythron and platelet counts occurred in rats exposed to
      2,000 mg/L; minimally impaired erythropoiesis was also seen in 1,000 mg/L rats.
      Liver weights of all exposed groups of males and females were significantly
      increased. Male rats in the 2,000 mg/L group had significantly decreased testis
      weights. Testicular atrophy was noted in the 2,000 mg/L group, and retained
      spermatids were observed in the 500 and 1,000 mg/L groups. In the pituitary gland
      of male rats exposed to 2,000 mg/L, the incidence of cellular hypertrophy was
      significantly increased. The incidences of hepatocellular vacuolization were
      significantly increased in males exposed to 500 mg/L or greater and in females
      exposed to 2,000 mg/L. Hematopoietic cell proliferation was noted in females in
      the 2,000 mg/L group. 3-MONTH STUDY IN MICE: Groups of 10 male and 10 female mice
      were exposed to 0, 125, 250, 500, 1,000, or 2,000 mg/L dibromoacetic acid
      (equivalent to average daily doses of approximately 16, 30, 56, 115, and 230
      mg/kg to males and 17, 34, 67, 132, and 260 mg/kg to females) in drinking water
      for 3 months. All mice survived to the end of the study. Mean body weights and
      body weight gains of female mice in the 2,000 mg/L group and the mean body weight
      gain of 2,000 mg/L males were significantly less than those of controls. Water
      consumption by males in the 2,000 mg/L group was decreased at weeks 1 and 13
      relative to controls. Small decreases in mean cell hemoglobin and platelet counts
      occurred in 2,000 mg/L male mice. Liver weights of males and females exposed to
      500 mg/L or greater were significantly increased. Hepatocellular cytoplasmic
      vacuolization was present in most mice and the severity was increased in 1,000
      and 2,000 mg/L males and females. The incidences of abnormal testicular
      morphology were significantly increased in 1,000 and 2,000 mg/L males. 2-YEAR
      STUDY IN RATS: Groups of 50 male and 50 female rats were exposed to drinking
      water containing 0, 50, 500, and 1,000 mg/L dibromoacetic acid for 2 years
      (equivalent to average daily doses of approximately 2, 20, and 40 mg/kg to males
      and 2, 25, and 45 mg/kg to females). Survival of exposed rats was similar to that
      of the control groups. Mean body weights of 1,000 mg/L males and females were
      less than those of the controls after weeks 29 and 53, respectively, and those of
      500 mg/L males and females were less after weeks 57 and 85, respectively. Water
      consumption by males and females exposed to 1,000 mg/L was less than that by
      controls during year 2 of the study. The incidence of malignant mesothelioma was
      significantly increased in 1,000 mg/L male rats. A positive trend in the
      incidence of mononuclear cell leukemia occurred in female rats, and the incidence
      in 1,000 mg/L females was significantly increased. The incidences of mononuclear
      cell leukemia were increased in 50 and 500 mg/L males. The incidences of cystic
      degeneration of the liver were significantly increased in all exposed groups of
      male rats. The incidences of alveolar epithelial hyperplasia were significantly
      increased in 500 and 1,000 mg/L females, and the incidences of nephropathy were
      significantly increased in all exposed groups of females. 2-YEAR STUDY IN MICE:
      Groups of 50 male and 50 female mice were exposed to drinking water containing 0,
      50, 500, and 1,000 mg/L dibromoacetic acid for 2 years (equivalent to average
      daily doses of approximately 4, 45, and 87 mg/kg to males and 4, 35, and 65 mg/kg
      to females). Survival of exposed mice was similar to that of the controls. Mean
      body weights of 50 and 500 mg/L male mice were greater than those of the controls
      after week 85. Water consumption by exposed mice was generally similar to that by
      controls throughout the study. The incidences of liver neoplasms occurred with
      positive trends in male and female mice. The incidences of multiple
      hepatocellular adenoma and hepatocellular adenoma or carcinoma (combined) were
      significantly increased in all exposed groups of males and in 500 and 1,000 mg/L
      females. The incidences of hepatoblastoma were significantly increased in 500 and
      1,000 mg/L males, and the incidences of hepatocellular carcinoma were
      significantly increased in 1,000 mg/L males and 500 mg/L females. The incidences
      of alveolar/bronchiolar adenoma occurred with positive trends in males and
      females, and the incidence in 500 mg/L male mice was significantly greater than
      that in controls. GENETIC TOXICOLOGY: Dibromoacetic acid was mutagenic in
      Salmonella typhimurium strain TA100 with and without rat or hamster liver
      metabolic activation enzymes (S9); no activity was detected in strain TA98, with
      or without S9. Increased frequencies of micronucleated normochromatic
      erythrocytes were observed in peripheral blood samples from male, but not female,
      mice administered dibromoacetic acid in drinking water for 3 months. CONCLUSIONS:
      Under the conditions of these studies, there was some evidence of carcinogenic
      activity of dibromoacetic acid in male rats based on an increased incidence of
      malignant mesothelioma. The increased incidences of mononuclear cell leukemia in
      male rats may have been related to dibromoacetic acid exposure. There was some
      evidence of carcinogenic activity of dibromoacetic acid in female rats based on
      an increased incidence and positive trend of mononuclear cell leukemia. There was
      clear evidence of carcinogenic activity of dibromoacetic acid in male and female
      mice based on increased incidences of hepatocellular neoplasms and hepatoblastoma
      (males only). Increased incidences of lung neoplasms in male mice were also
      considered to be exposure related. The slight increased incidence of lung
      neoplasms in female mice may have been related to dibromoacetic acid exposure.
      Exposure to dibromoacetic acid for 2 years caused increased incidences of cystic
      degeneration of the liver in male rats, increased incidences of alveolar
      epithelial hyperplasia and nephropathy in female rats, and increased incidences
      of splenic hematopoiesis in male mice.

PMID- 17554400
TI  - Self-reported sickness absence as a risk marker of future disability pension.
      Prospective findings from the DWECS/DREAM study 1990-2004.
AB  - OBJECTIVES: This prospective cohort study examines number of self-reported days
      of sickness absence as a risk marker for future disability pension among a
      representative sample of employees in Denmark 1990-2004. MATERIAL AND METHODS:
      4177 employees between 18 and 45 years were interviewed using a self-administered
      questionnaire in 1990 regarding sickness absence, age, gender, socioeconomic
      position, health behaviour, and physical and psychosocial work environment. They
      were followed for 168 months in a national disability pension register. Logistic
      regression analysis was performed in order to assess risk estimates for levels of
      absence and future disability pension. RESULTS: During follow-up, a total of 140
      persons (3.4%) received disability pension. Of these, 82 (58.6%) were women, 58
      (41.4%) were men. There was a 2.5 fold risk of future disability pension for the
      part of the population reporting more than 6 days of sickness absence per annum
      at baseline, when taking into account gender, age, socioeconomic position, health
      behaviour, physical and psychosocial work environment. CONCLUSION: The findings
      suggest that information on self-reported days of sickness absence can be used to
      effectively identify "at risk" groups for disability pension.

PMID- 17554399
TI  - Efficiency of vibration exercise for glycemic control in type 2 diabetes
      patients.
AB  - Although it is well documented that persons suffering from diabetes type 2 profit
      from muscular activities, just a negligible amount of patients take advantage of
      physical exercises. During the last decade, vibration exercise (VE) could be
      established as an effective measure to prevent muscular atrophy and osteoporosis
      with low expenditure of overall exercise-time. Unfortunately, little is known
      about the metabolic effects of VE. In the present study we compared VE with the
      influence of strength training and a control group (flexibility training) on
      glycemic control in type 2 diabetes patients. Forty adult non-insulin dependent
      patients participated in the intervention. Fasting glucose concentration, an oral
      glucose tolerance test (OGTT), haemoglobin A1c (HbA1c), the isometric maximal
      torque of quadriceps muscles, and endurance capacity were evaluated at baseline
      and after 12 weeks of training with three training sessions per week. The main
      findings are: Fasting glucose concentrations remind unchanged after training. The
      area under curve and maximal glucose concentration of OGTT were reduced in the
      vibration and strength training group. HbA1c values tended to decrease below
      baseline date in the vibration training group while it increased in the two other
      intervention groups. Theses findings suggest that vibration exercise may be an
      effective and low time consuming tool to enhance glycemic control in type 2
      diabetes patients.

PMID- 17554401
TI  - A novel variable number of tandem repeat of the natriuretic peptide precursor B
      gene's 5'-flanking region is associated with essential hypertension among
      Japanese females.
AB  - BACKGROUND: Brain natriuretic peptide (BNP) acts primarily as a cardiac hormone;
      it is produced by the ventricle and has both vasodilatory and natriuretic
      actions. Therefore, the BNP gene is thought to be a candidate gene for essential
      hypertension (EH). The present study identified variants in the 5'-flanking
      region of natriuretic peptide precursor B (NPPB) gene and assessed the
      relationship between gene variants and EH. METHODS: The polymerase chain reaction
      single strand conformation polymorphism method and nucleotide sequencing were
      used to identify variants. RESULTS: A novel variable number of tandem repeat
      (VNTR) polymorphism in the 5'-flanking region (-1241 nucleotides from the major
      transcriptional initiation site) was discovered. This VNTR polymorphism is a
      tandem repeat of the 4-nucleotide sequence TTTC. There were 8 alleles, ranging
      from 9-repeat to 19-repeat. An association study was done involving 317 EH
      patients and 262 age-matched normotensive (NT) subjects. The 11-repeat allele was
      the most frequent (88.2%); the 16-repeat allele was the second most frequent
      (10.5%) in the NT group. The observed and expected genotypes were in agreement
      with the predicted Hardy-Weinberg equilibrium values (P=0.972). Among females,
      the overall distribution of genotypes was significantly different between the EH
      and NT groups (p=0.039). The frequency of the 16-repeat allele was significantly
      lower in the female EH group (6.5%) than in the female NT group (12.2%, p=0.046).
      CONCLUSIONS: The 16-repeat allele of the VNTR in the 5'-flanking region of NPPB
      appears to be a useful genetic marker of EH in females.

PMID- 17554402
TI  - High-risk, clinically localized prostate cancer: is monotherapy adequate?
AB  - High-risk, clinically localized prostate cancer represents a diverse disease
      entity. Patients who are considered to be at highest risk for biochemical failure
      after localized treatments may not be at significant risk for disea-sespecific
      mortality. In this review, an attempt will be made to define high-risk status and
      help identify patients at high risk for mortality after a diagnosis of localized
      prostate cancer. Subsequently, a review of monotherapy approaches as well as
      previously successful strategies utilizing multimodality therapy for high-risk
      disease will be presented. Finally, a synopsis will be given of several ongoing
      randomized clinical trials using the most effective systemic therapies in the
      adjuvant setting following thorough local treatments such as radical
      prostatectomy. This review will provide a glimpse into the future and describe
      the tools that it is hoped will improve further upon the results of surgical
      monotherapy for high-risk, localized prostate cancer.

PMID- 17554403
TI  - New paradigms for advanced prostate cancer.
AB  - In men with metastatic hormone-refractory prostate cancer, androgen blockade
      produces dramatic and rapid declines in prostate-specific antigen (PSA), bone
      pain, and urinary tract obstruction. Nevertheless, there have been limited
      options with at best palliative results for patients who progress despite a
      castrate testosterone level. This paradigm changed in 2004 with the publication
      of 2 randomized clinical trials that demonstrated a 20% to 24% survival benefit
      for docetaxel-based therapy when compared to mitoxantrone and prednisone, data
      that supported US Food and Drug Administration approval of docetaxel-based
      therapy for the treatment of metastatic hormone-refractory prostate cancer. This
      article reviews the preliminary data and the timing and sequencing implications
      of ongoing clinical trials. Studies are evaluating the combination of docetaxel
      with agents that target bone, tumor vasculature, and the vitamin D receptor as
      well as second-line agents, such as satraplatin. The role of immune therapy is
      also evolving, and further studies will define the optimal timing of chemotherapy
      with immune therapy.

PMID- 17554405
TI  - Treatment options for hormone-refractory prostate cancer.
AB  - Hormone-refractory prostate cancer is a disease that includes a variety of
      patients and represents a treatment dilemma for the practicing physician. Because
      of the diversity of this group, management strategies must be targeted to the
      clinical situations of the individual patients and their wishes. This article
      outlines a logical progression of treatment choices that currently exist in this
      rapidly evolving field, and the landmark chemotherapy trials involving docetaxel
      (SWOG 9916 and TAX 327) are reviewed. Although significant progress has been made
      in understanding and treating hormone-refractory prostate cancer, current
      treatments do not yet provide a cure, and important clinical trials continue to
      recruit patients.

PMID- 17554404
TI  - Breast cancer clinical and translational research: analogies and implications for
      prostate cancer.
AB  - Breast and prostate cancer, respectively, are the most common cancers in women
      and in men in the United States. The management of locally advanced prostate
      cancer involves a multidisciplinary approach, bearing similarity to the
      therapeutic approach to breast cancer. Better understanding of the molecular
      biology of these cancers and the identification of the role played by the cancer
      stem cells and the tumor microenvironment may translate into better clinical
      decision making regarding risk classification and treatment allocation. A
      systematic assessment is presented of the many parallel evolutions in defining
      and treating high-risk breast cancer as they pertain to prostate cancer.

PMID- 17554406
TI  - Mass spectrometric identification of peptide hormones in doping-control analysis.
AB  - The identification power of mass spectrometry has enabled the determination of
      hundreds of prohibited drugs in doping-control analysis. A few years ago, its
      utility was extended to peptide hormones such as erythropoietins, synthetic
      insulins and corticotrophins detectable in blood or urine. New assays have been
      established to improve the fight against doping, employing highly selective and
      sensitive detection methods based on chromatographic and tandem mass
      spectrometric techniques. In particular, in light of recent scandals related to
      assumed peptide hormone misuse and attempts at the alteration of urine,
      sophisticated analytical tools are essential for obtaining unequivocal results in
      sports drug testing.

PMID- 17554407
TI  - Discrimination of prostate cancer cells by reflection mode FTIR photoacoustic
      spectroscopy.
AB  - In this communication reflection mode Fourier transform infrared photoacoustic
      spectroscopy (FTIR-PAS) is used to obtain IR spectra of four prostate and
      prostate cancer cell line types (CaP) allowing their differentiation by principal
      components analysis.

PMID- 17554408
TI  - Direct electrical detection of antigen-antibody binding on diamond and silicon
      substrates using electrical impedance spectroscopy.
AB  - The integration of biological molecules with semiconducting materials such as
      silicon and diamond has great potential for the development of new types of
      bioelectronic devices, such as biosensors and bioactuators. We have investigated
      the electrical properties of the antibody-antigen modified diamond and silicon
      surfaces using electrical impedance spectroscopy (EIS). Frequency dependent
      measurements at the open-circuit potential show: (a) significant changes in
      impedance at frequency >10(4) Hz when the surface immobilized IgG was exposed to
      anti-IgG, and (b) only little or no change when exposed to anti-IgM. Mott
      Schottky measurements at high frequency (200 kHz) show that the impedance is
      dominated by the space charge layer of the semiconducting substrates. Silicon
      surfaces modified in a similar manner to the diamond surface are compared; n-type
      and p-type samples show complementary behavior, as expected for a field effect.
      We also show it is possible to directly observe antigen-antibody interaction at a
      fixed frequency in real time, and with no additional labeling.

PMID- 17554409
TI  - Direct and rapid discrimination of aflatoxigenic strains based on fibre-optic
      room temperature phosphorescence detection.
AB  - An innovative analytical methodology for the rapid identification of aflatoxin
      producing moulds belonging to Aspergillus genus is presented here. The procedure
      is based on the measurement, using a fibre-optic luminometer, of the room
      temperature phosphorescence (RTP) emitted by aflatoxins produced by isolated
      aflatoxigenic strains, cultured in a special culture medium consisting of malt
      extract agar modified with beta-cyclodextrin and sodium deoxycholate for RTP
      induction. Unequivocal detection of the presence of aflatoxins in the culture
      medium is achieved within the first 36 h of incubation at 32 degrees C, owing to
      the selectivity and sensitivity of the RTP emission, as compared with the minimum
      of 72 h needed using a conventional microbiological method. In a first step, the
      capability of aflatoxin standard solutions to emit analytically useful RTP was
      evaluated. In this line all experimental conditions were optimised for in vitro
      induction of RTP from aflatoxins. In a second step, a simple analytical test was
      developed and it has been evaluated for the rapid identification of aflatoxigenic
      strains, as a discriminating assay from non-aflatoxigenic strains based on the
      measurement of experimental RTP emission observed. Confirmation of aflatoxin
      production on the studied culture plates was accomplished by means of an
      HPLC/fluorescence reference method.

PMID- 17554410
TI  - An impedimetric immunosensor for the detection of autoantibodies directed against
      gliadins.
AB  - An immunosensor has been developed for the detection of autoantibodies directed
      against wheat gliadin, a protein fraction of cereal gluten which is involved in
      celiac disease. The immunosensor is based on the immobilization of gliadins onto
      gold electrodes covered with a polyelectrolyte layer of poly(4-styrenesulfonic
      acid sodium salt). The immobilization was monitored by quartz crystal
      microbalance (QCM) analysis. The antigen-antibody interaction signal was
      amplified by an incubation step with peroxidase-labeled immunoglobulins and
      subsequent peroxidase-catalyzed oxidation of 3-amino-9-ethylcarbazole (AEC).
      Changes in the insulating properties of the electrode layer were measured by
      electrochemical impedance spectroscopy (EIS) in the presence of ferri/ferro
      cyanide. Impedance spectra could be fitted to a Randles equivalent circuit with
      high accuracy. Exposing the sensor electrodes to various antigliadin antibody
      concentrations resulted in proportional changes in the charge transfer
      resistance. A calibration graph for the detection of antigliadin antibodies was
      established for antibody concentrations between 10(-8) and 10(-6) M. Finally, the
      sensor was used for the determination of antigliadin autoantibodies of the IgG
      and IgA type in several human sera.

PMID- 17554411
TI  - Electrochemical valveless flow microsystems for ultra fast and accurate analysis
      of total isoflavones with integrated calibration.
AB  - A novel strategy integrating methodological calibration and analysis on board on
      a planar first-generation microfluidics system for the determination of total
      isoflavones in soy samples is proposed. The analytical strategy is conceptually
      proposed and successfully demonstrated on the basis of (i) the microchip design
      (with the possibility to use both reservoirs), (ii) the analytical
      characteristics of the developed method (statically zero intercept and excellent
      robustness between calibration slopes, RSDs < 5%), (iii) the irreversible
      electrochemical behaviour of isoflavone oxidation (no significant electrode
      fouling effect was observed between calibration and analysis runs) and (iv) the
      inherent versatility of the electrochemical end-channel configurations
      (possibility of use different pumping and detection media). Repeatability
      obtained in both standard (calibration) and real soy samples (analysis) with
      values of RSD less than 1% for the migration times indicated the stability of
      electroosmotic flow (EOF) during both integrated operations. The accuracy (an
      error of less than 6%) is demonstrated for the first time in these microsystems
      using a documented secondary standard from the Drug Master File (SW/1211/03) as
      reference material. Ultra fast calibration and analysis of total isoflavones in
      soy samples was integrated successfully employing 60 s each; enhancing notably
      the analytical performance of these microdevices with an important decrease in
      overall analysis times (less than 120 s) and with an increase in accuracy by a
      factor of 3.

PMID- 17554412
TI  - Quantitative determination of ethanol in heated plumes by passive Fourier
      transform infrared remote sensing measurements.
AB  - Quantitative calibration models are developed for passive Fourier transform
      infrared (FT-IR) remote sensing measurements of open-air-generated vapors of
      ethanol. These experiments serve as a feasibility study for the use of passive FT
      IR measurements in quantitative determinations of industrial stack emissions. A
      controlled-temperature plume generator is used to produce plumes of known
      concentrations of pure ethanol and mixtures of ethanol and methanol. Analyte
      plumes are generated over the path-averaged concentration range of 20-300 ppm-m
      and stack temperatures of 125, 150, 175, and 200 degrees C. A novel experimental
      setup is employed in which an ambient temperature polyvinyl chloride backdrop is
      placed behind the emission stack and used as a target for the passive IR
      measurements. An emission FT-IR spectrometer with telescope entrance optics is
      then employed to view the generated plumes against the backdrop. Signal
      processing techniques based on signal averaging and bandpass digital filtering
      are applied to both interferogram and single-beam spectral data obtained from
      these measurements, and the resulting filtered signals are used as inputs into
      the generation of multivariate partial least-squares (PLS) calibration models.
      Successful calibration models are obtained with both interferogram and spectral
      data, and neither analysis requires the collection of separate IR background
      data. For a set of validation data collected on a different day from the
      calibration measurements, standard errors of prediction of 30.6 and 32.2 ppm-m
      ethanol are obtained for the PLS models based on interferogram and spectral data,
      respectively.

PMID- 17554413
TI  - A wireless magnetoelastic biosensor for the direct detection of organophosphorus
      pesticides.
AB  - An organophosphorus (OP) pesticide sensor was fabricated by applying a pH
      sensitive polymer coating and organophosphorus hydrolase (OPH) enzyme onto the
      surface of a magnetoelastic sensor, the magnetic analogue of the better-known
      surface acoustic wave sensor. Organophosphorus hydrolase catalyses the hydrolysis
      of a wide range of organophosphorus compounds, which changes the pH in the
      hydrogel. This article describes the application of the magnetoelastic sensor for
      the detection of OP pesticides by measuring the changes in viscoelasticity caused
      by the swelling/shrinking of the pH-responsive polymer when exposed to the
      pesticides. The sensor was successfully used to detect paraoxon and parathion
      down to a concentration of 1 x 10(-7) and 8.5 x 10(-7) M respectively.

PMID- 17554414
TI  - The use of Zipf's law in the screening of analytical data: a step beyond Benford.
AB  - This study shows for the first time the effectiveness of Zipf's law in screening
      analytical data sets for outliers, data formatting and data transcription errors,
      particularly when the data sets are small. In the case of pollutant
      concentrations in ambient air, the multivariate nature of the measurement, and
      the relationship between the measured values of these multivariant quantities are
      the characteristics that allow a Zipf's law approach to data screening to be
      successful. Furthermore, it has been shown that Zipf's law has advantages over
      other novel data screening techniques, such as Benford's law, in terms of
      sensitivity and scope.

PMID- 17554415
TI  - Chronocoulometric determination of nitrate on silver electrode and sodium
      hydroxide electrolyte.
AB  - An electrochemical system that consists of a silver electrode in 0.01 M sodium
      hydroxide electrolyte was investigated in an effort to develop a sensitive in
      situ analytical method for nitrate. Cyclic voltammetry demonstrated that the
      proposed system has a high normalized sensitivity (2.47 A s(1/2) V(-1/2) M(-1)
      cm(-2)), compared to more complex electroanalytical schemes. Double-potential
      step chronocoulometry was used to maximize the signal-to-noise ratio (SNR), and
      minimize interference from dissolved oxygen in the electrolyte. The integration
      period for double-potential-step chronocoulometry was determined by optimizing
      the extended Cottrell equation. The integrated current is proportional to nitrate
      up to 10 mM and the average detection limit is approximately 1.7 microM.
      Dissolved oxygen does not degrade performance. To examine the potential
      interference of other ions when analyzing nitrate, we measured the electrode
      response to 1000 microM each of NO(2-), Cl(-), PO(4)(3-), SO(4)(2-), F(-),
      CO(3)(2-), BO(2-), K(+), Ca(2+), and Sr(2+) with and without 1000 microM nitrate.
      Interference is negligible for most of the ions when nitrate is absent (i.e. <1%
      of the response to equimolar nitrate). However, interference is substantial (>20%
      increase or decrease in the electrode response to nitrate) for PO(4)(3-), Ca(2+),
      and Sr(2+) when equimolar nitrate is present.

PMID- 17554416
TI  - High sequence-coverage detection of proteolytic peptides using a
      bis(terpyridine)ruthenium(II) complex.
AB  - The use of a bis(terpyridine)ruthenium(ii) complex for peptide labeling (Ru-CO
      labeling) supplied high intensity peaks in mass spectrometry (MS) analysis that
      overcame the contribution of protonation or sodiated adduction to peptides. Ru-CO
      labeled insulin A- and B-chains were detected simultaneously in comparable peak
      abundance by matrix-assisted laser desorption/ionization time-of-flight mass
      spectrometry (MALDI-TOF-MS). The mass spectra of chymotryptic peptide fragments
      of Ru-CO-labeled insulin also simultaneously indicated both N-terminal fragment
      ions, and amino acid sequences were determined easily by matrix-assisted laser
      desorption/ionization post-source-decay (MALDI-PSD). The sensitivity of detecting
      Ru-CO-labeled peptide fragment ions was not dependent on the length or the
      sequences of the peptides. The Ru-CO labeling method was applied to tryptic
      myoglobin fragments. The method indicated that each fragment ion is detected
      nearly equal in abundance and enabled the desired fragment ions to be
      distinguished from matrix clusters or their in-source fragments in lower mass
      regions. The desired fragment ions can be found in the mass region higher than
      670.70 (= Ru-CO). This method provided a high sequence coverage (96%) by peptide
      mass fingerprinting (PMF). Application of this method to a protein mixture
      (myoglobin, lysozyme and ubiquitin) successfully achieved high sequence-coverage
      characterization (>90%) of these proteins simultaneously.

PMID- 17554417
TI  - Redox cycling with facing interdigitated array electrodes as a method for
      selective detection of redox species.
AB  - A pair of interdigitated ultramicroelectrodes (UMEs) is used to electrochemically
      detect a weak reductor (dopamine) in the presence of a stronger one
      (K(4)[Fe(CN)(6)]). In the mixture of both reductors, one of the two
      interdigitated electrodes (the generator electrode) is used to oxidize both
      species at 700 mV vs. Ag/AgCl, followed by subsequent (selective) reduction of
      the oxidized dopamine at 400 mV. A regenerated dopamine molecule can thus be
      oxidized several times (redox cycling) and enable selective detection even in the
      presence of the stronger reductor. In order to obtain high redox cycling
      efficiency, we designed and realized platinum electrodes with widths of 2 and 4
      microm and spacing of 2 microm, which gave redox cycling efficiencies of 9 and 4
      respectively. Using this electrode design, a dopamine/K(4)[Fe(CN)(6)] selectivity
      of 2 could be obtained.

PMID- 17554420
TI  - Occupational and indoor air exposure to persistent organic pollutants: a review
      of passive sampling techniques and needs.
AB  - Exposure to persistent organic pollutants (POPs) and related compounds such as
      PCBs, brominated flame retardants, organochlorine pesticides and PAHs is regarded
      as an important environmental risk factor for humans. Recently concerns about
      POPs resulted in the international protocol called the Stockholm Convention on
      POPs. Air quality standards (indoor, outdoor and occupational) for PAHs and other
      POPs will also be applied in the EU in the future. This will bring requirements
      for monitoring, to check for compliance and to reduce human exposures to POPs.
      This can occur from point sources and in various microenvironments, indoors,
      outdoors and in workplaces. Monitoring can be undertaken either by an active
      (pumped) method or using a passive (diffusive) air sampling (PAS) device. To
      date, PAS for POPs have mainly been used as integrating (long-term) samplers for
      ambient (outdoor) air. However, there are several reasons to develop PAS for
      monitoring of POPs in occupational and indoor environments. We discuss the
      potential advantages, limitations and developments needed, so that PAS can be
      used reliably and routinely indoors and in occupational settings for POPs.

PMID- 17554421
TI  - Development of microbial degradation of cypermethrin and diazinon in organically
      and conventionally managed soils.
AB  - The behaviour of pesticides in the soil is a complex issue and is controlled by
      the physical, chemical and biological properties of the soil. The ability of
      microorganisms to degrade pesticides is not only controlled by the
      bioavailability of a chemical but also by their capacity to develop the ability
      to utilise available chemicals. The development of catabolism in the indigenous
      soil microflora of four organically and one conventionally managed soils was
      investigated for two pesticides: cypermethrin and diazinon. Soils were amended
      with cypermethrin and diazinon and aged for 0, 2, 4, 6, 8, and 14 weeks and, at
      each time point, mineralisation of freshly added 14C-cypermethrin or 14C-diazinon
      was measured by trapping 14CO2. In general, contact times between the soil and
      the pesticide resulted in a reduction in the lag phase (the period of time before
      mineralisation exceeded 5% of the added activity), followed by increases in the
      extent of mineralisation. Cypermethrin was mineralised significantly in all
      soils; whereas, diazinon was only appreciably mineralised in two of the soils,
      most notably in the organic soil from Redesdale. Statistical analysis showed pH
      and organic matter content of the soil had a significant effect on the extent of
      mineralisation (P< or = 0.05) of the cypermethrin in the soils.

PMID- 17554422
TI  - Prediction of PAH biodegradation in field contaminated soils using a cyclodextrin
      extraction technique.
AB  - Biodegradation has been identified as a major loss process for organic
      contaminants in soils and, as a result, microbial strategies have been developed
      for the remediation of contaminated land. Prediction of the biodegradable
      fraction would be important for determining bioremediation end-points in the
      clean-up of contaminated land. The aim of this study was to investigate the
      ability of a cyclodextrin extraction to predict the extent to which polycyclic
      aromatic hydrocarbons (PAHs) would be degraded microbiologically in field
      contaminated soils; further testing the robustness and reproducibility of this
      extraction in chemically complex systems. Dichloromethane and hydroxypropyl-beta
      cyclodextrin (HPCD) extractable fractions were measured together with the PAH
      biodegradable fraction in each of the six field contaminated soils. The amounts
      of PAHs degraded by the catabolic activity of the indigenous microflora in each
      of the soils were correlated with HPCD-extractable PAH concentrations. The
      regressions showed that the amounts of lower molecular weight PAHs extracted by
      the HPCD were not significantly (P > 0.05) different to the amounts that were
      degraded. However, higher molecular weight PAHs that were extracted by HPCD did
      differ significantly (P < 0.05) from the amounts degraded. Although the HPCD
      extraction did overestimate the microbially degradable fraction of the higher
      molecular weight PAHs, overall the correlations between the HPCD extractable
      fraction and the microbially degradable fraction were very close, with mean
      values of the slope of line for the six soils equalling 1. This study further
      describes the robust and reproducible nature of the aqueous-based soil extraction
      technique reliably measuring the extent to which PAHs will be microbially
      degraded in soil.

PMID- 17554423
TI  - In utero and post-natal accumulation of organochlorine compounds in children
      under different environmental conditions.
AB  - A study of intake of organochlorine compounds (OCs) in children both in utero and
      at the age of four years has been performed in two cohorts. One encompasses
      children born in Menorca Island between 1997 and 1998, and the other those born
      between 1997-1999 in Ribera d'Ebre, an in-land industrial-agricultural area of
      Catalonia. Comparison of the OC concentrations in serum samples from both
      populations, including those obtained from cord blood and blood collected at four
      years, provides information on the influence of local pollution sources in the
      accumulation of these compounds. Statistically significant differences (p < 0.01)
      have been found for hexachlorobenzene, indicating that chronic airborne
      contamination to this compound in Ribera d'Ebre involved higher in utero
      exposure, which increased in the first four years of growth. Similarly, in the
      cohort of Menorca, higher in utero exposure to PCBs was observed and this
      increased subsequently in the first four years of growth. Other compounds
      encompassing temporal contamination episodes such as gamma-HCH involved higher in
      utero exposure but strongly diminished in the first four years of growth.
      Overall, it can be concluded that local chronic pollution by OCs has a direct
      effect in children living in the surrounding areas. This influence is reflected
      in higher exposure, both in utero and in the first years of growth, that
      significantly stands out over the background contamination due to the ubiquity of
      these compounds.

PMID- 17554424
TI  - Analysis of per- and polyfluorinated alkyl substances in air samples from
      Northwest Europe.
AB  - Air samples were collected from 4 field sites in Europe: 2 sites from the UK,
      Hazelrigg (semi-rural) and Manchester (urban); 1 site from Ireland: Mace Head
      (rural); and 1 site from Norway: Kjeller (rural). Additionally, air samples were
      taken from indoor locations in Tromso, Norway. Air samples were collected using
      high-volume air samplers employing sampling modules containing glass-fibre
      filters (GFFs, particle phase), and glass columns with a polyurethane foam (PUF)
      XAD-2-PUF sandwich (gaseous phase). Typical outdoor air volumes required for the
      determination of per- and polyfluorinated alkyl substances (PFAS) ranged from 500
      1800 m3. GFFs and PUF-XAD columns were analysed separately to obtain information
      on phase partitioning. All air samples were analysed for volatile, neutral PFAS,
      with selected GFF samples halved for analysis of both neutral and airborne
      particle-bound ionic PFAS. Volatile PFAS were extracted from air samples by cold
      column immersion with ethyl acetate, and were analysed by gas chromatography-mass
      spectrometry in the positive chemical ionisation mode (GC-PCI-MS). Ionic PFAS
      were extracted from GFFs by sonication in methanol, and were analysed by liquid
      chromatography-time-of-flight-mass spectrometry (LC-TOF-MS) using electrospray
      ionisation in the negative ion mode (ESI-). Perfluorooctanoate (PFOA) was often
      the predominant analyte found in the particulate phase at concentrations ranging
      from 1-818 pg m(-3), and 8:2 fluorotelomer alcohol (FTOH) and 6:2 FTOH were the
      prevailing analytes found in the gas phase, at 5-243 pg m(-3) and 5-189 pg m(-3),
      respectively. These three PFAS were ubiquitous in air samples. Many other PFAS,
      both neutral and ionic, were also present, and levels of individual analytes were
      in the 1-125 pg m(-3) range. Levels of some PFAS exceeded those of traditional
      persistent organic pollutants (POPs). In this study, the presence of 12:2 FTOH
      and fluorotelomer olefins (FTolefins), and ionic PFAS other than perfluorooctane
      sulfonate (PFOS) and PFOA, are reported in air samples for the first time.
      Concentrations of neutral PFAS were several orders of magnitude higher in indoor
      air than outdoor air, making homes a likely important diffuse source of PFAS to
      the atmosphere. Our repeated findings of non-volatile ionic PFAS in air samples
      raises the possibility that they might directly undergo significant atmospheric
      transport on particles away from source regions, and more atmospheric
      measurements of ionic PFAS are strongly recommended.

PMID- 17554425
TI  - Tracing the fate of PCBs in forest ecosystems.
AB  - Forests were shown to play an important role in influencing atmospheric
      concentrations and transport of persistent organic pollutants (POPs) in the
      environment. World forests cover more than 4 billion hectares and contain up to
      80% of the above ground organic carbon. Given the lipophilic nature of POPs, this
      suggests that forests can influence the environmental fate of POPs at a global
      scale. POP accumulation in forest canopies still presents points of concern given
      the complexity of these ecosystems. In particular, the role of ecological
      parameters such as LAI (leaf area index) and SLA (specific leaf area) and their
      dynamics during the growing season was not sufficiently investigated yet. This
      paper reviews, compares and interprets a unique case study in which air and leaf
      concentrations and deposition fluxes for selected polychlorinated biphenyls
      (PCBs) were measured in three different forest types exposed to the same air
      masses. In order to trace the air-leaf-soil path of these compounds, a dynamic
      model of POP accumulation into forest canopy was applied. The dynamics of the
      canopy biomass strongly affected the trend of leaf concentration with time.
      Growth dilution effect can prevent the more chlorinated compounds from reaching
      the partitioning equilibrium before litter fall, while the more volatile
      compounds can approach equilibrium in the range of few weeks. An amount of up to
      60 ng of PCBs per square metre of ground surface was predicted to be stored in
      each of the selected forests at fully developed canopy. Dry gaseous deposition
      fluxes to forest canopy were estimated to reach a maximum value of about 0.5-1.5
      ng m(-2) d(-1) during the spring period.

PMID- 17554426
TI  - Spatial variation in concentrations and patterns of the PCDD/F and dioxin-like
      PCB content in herring from the northern Baltic Sea.
AB  - The purpose of the current study was to investigate spatial and seasonal
      variation of dioxin and dioxin-like PCB (dl-PCB) content in herring sampled along
      the northern Baltic Sea coast and map out risk zones for dioxins and dl-PCBs. We
      further aimed to investigate relationships between congener distribution
      (pattern) and sampling location and season. The results showed that there were
      distinct geographical differences in concentrations of dioxins, dibenzofurans and
      dl-PCBs along the Swedish coast, from the Bothnian Bay to north Baltic Proper,
      with the highest levels detected in the southern Bothnian Sea. The majority of
      the locations showed concentrations above the prescribed maximum for dioxin
      residues (4 TEQ pg g(-1) wet weight [w.w.]). If all the edible parts of the fish
      (muscle, subcutaneous fat and skin) are considered, the estimated concentrations
      exceeded the prescribed maximum level in the whole study area for herring
      collected during spring-summer. Concentrations in herring caught during spring
      summer compared to concentrations in herring sampled in the autumn indicated
      seasonal variation. The pattern analysis showed a variation in relative congener
      concentration at the different sampling locations (spring-summer). Pattern
      differences were also noticed between seasons.

PMID- 17554427
TI  - Trends in background levels of persistent organic pollutants at Kosetice
      observatory, Czech Republic.1) Part I. Ambient air and wet deposition 1996-2005.
AB  - Kosetice observatory is a facility of the Czech Hydrometeorological Institute,
      which is a part of the European Monitoring and Evaluation Programme (EMEP)
      network. Persistent organic pollutants (POPs: PCBs, DDTs, HCHs, PAHs) have been
      monitored in all environmental matrices using the integrated monitoring approach.
      Generally, the atmospheric levels of POPs in this Central European background
      station (mean values: 0.115 ng m(-3) for SigmaPCBs, 0.040 ng m(-3) for SigmaDDTs,
      0.077 ng m(-3) for SigmaHCHs, and 17 ng m(-3) for SigmaPAHs) are significantly
      higher than those in other EMEP stations localized mostly in Northern and Western
      Europe. Long-term trends of POP concentrations in the ambient air and wet
      deposition are presented in this article and they show a slow decline in the last
      decade for most of the investigated compounds. Temporally increased levels of
      certain chemicals were associated with some local climatic (floods) or socio
      economic (fuel prices) factors.

PMID- 17554428
TI  - Trends in background levels of persistent organic pollutants at Kosetice
      observatory, Czech Republic.2) Part II. Aquatic and terrestrial environments 1996
      2005.
AB  - A multimedia sampling of ambient air, wet deposition, surface water, sediment,
      soil and biota has been performed at Kosetice background observatory in the
      southern Czech Republic since 1988. An integrated monitoring approach was applied
      to assess the current state, anthropogenic impacts, and possible future changes
      of terrestrial and freshwater environments. Average PCB concentrations in the
      individual matrices calculated from ten years of sampling on multiple sites
      varied between 2 ng g(-1) in sediment and 7 ng g(-1) in soil or moss. DDT
      concentrations were lower in moss and needles (2 ng g(-1) and 4 ng g(-1),
      respectively) than in sediment (11 ng g(-1)) and soil (20 ng g(-1)), while the
      HCH level was higher in moss and needles (5 ng g(-1) and 6 ng g(-1),
      respectively) than in soil or sediment (1 ng g(-1) and 2 ng g(-1), respectively).
      The highest average level of PAHs was found in soil (600 ng g(-1)), while it was
      lower in needles (230 ng g(-1)), moss (210 ng g(-1)) or sediment (210 ng g(-1)).
      Time related trends of concentration levels of persistent organic pollutants in
      all matrices were investigated. Moss and needle trend patterns resembled those of
      the ambient air, showing a slight concentration decrease of all compounds, except
      for hexachlorobenzene. The soil, water and sediment concentrations showed a
      similar decrease of PAHs, PCBs, and HCHs, but there was no clear trend for DDTs
      and HCB.

PMID- 17554429
TI  - Empirical evaluation of spatial and non-spatial European-scale multimedia fate
      models: results and implications for chemical risk assessment.
AB  - Multimedia environmental fate models are commonly-applied tools for assessing the
      fate and distribution of contaminants in the environment. Owing to the large
      number of chemicals in use and the paucity of monitoring data, such models are
      often adopted as part of decision-support systems for chemical risk assessment.
      The purpose of this study was to evaluate the performance of three multimedia
      environmental fate models (spatially- and non-spatially-explicit) at a European
      scale. The assessment was conducted for four polycyclic aromatic hydrocarbons
      (PAHs) and hexachlorobenzene (HCB) and compared predicted and median observed
      concentrations using monitoring data collected for air, water, sediments and
      soils. Model performance in the air compartment was reasonable for all models
      included in the evaluation exercise as predicted concentrations were typically
      within a factor of 3 of the median observed concentrations. Furthermore, there
      was good correspondence between predictions and observations in regions that had
      elevated median observed concentrations for both spatially-explicit models. On
      the other hand, all three models consistently underestimated median observed
      concentrations in sediment and soil by 1-3 orders of magnitude. Although regions
      with elevated median observed concentrations in these environmental media were
      broadly identified by the spatially-explicit models, the magnitude of the
      discrepancy between predicted and median observed concentrations is of concern in
      the context of chemical risk assessment. These results were discussed in terms of
      factors influencing model performance such as the steady-state assumption,
      inaccuracies in emission estimates and the representativeness of monitoring data.

PMID- 17554430
TI  - Passive air sampling of DDT, chlordane and HCB in the Pearl River Delta, South
      China: implications to regional sources.
AB  - The Pearl River Delta (PRD) is one of the largest fast-developing economic zones
      in China. Hong Kong and the mainland part of the PRD differed in socio-economic
      development history and chemical management policies. Polyurethane foam (PUF)
      passive air sampling (PAS) was deployed at 21 regional air quality monitoring
      stations across the PRD in summer and winter, respectively. Dichloro-diphenyl
      trichloroethane (DDT), chlordane and hexachlorobenzene (HCB) were analyzed with
      GC-MS. High total DDT (240-3700 pg m(-3)) and chlordane (100-2600 pg m(-3))
      concentrations were observed. Concentrations of DDTs and chlordane were higher in
      summer than winter; HCB vice versa. Spatially, the mainland part of the PRD
      generally displayed higher DDT concentrations than Hong Kong. Antifouling paint
      for fishing ships in coastal China was suggested to be an important current DDT
      source in the coast. The reason is unknown for the very low trans-/cis-chlordane
      (TC/CC) ratios (0.27) found in the mainland in winter. HCB concentrations were
      relatively uniform across the PRD, and long range transport of HCB from
      inland/North China to the PRD in winter was suggested.

PMID- 17554431
TI  - Occurrence of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs),
      polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) in
      Lake Maggiore (Italy and Switzerland).
AB  - Samples of air (gas and particulate phases), bulk deposition, aquatic settling
      material and sediments were collected in Lake Maggiore (LM) in order to determine
      their content of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs),
      polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs). Air
      (gas and particulate phases) concentrations were 0.5 pg m(-3), 80 pg m(-3), 13 pg
      m(-3) and 106 pg m(-3) for SigmaPCDD/Fs, SigmaPCBs, Sigma dioxin-like PCBs (DL
      PCBs) and SigmaPBDEs, respectively. Deposition fluxes ranged from 0.7 ng m(-2) d(
      1) for SigmaPCDD/Fs to 32 ng m(-2) d(-1) for SigmaPCBs. Aquatic settling material
      presented concentrations of 0.4 ng g(-1) dry weight (dw) for SigmaPCDD/Fs, 13 ng
      g(-1) dw for SigmaPCB, 3.4 ng g(-1) dw for SigmaDL-PCBs and 5.7 ng g(-1) dw for
      SigmaPBDEs. Mean sediment concentrations were 0.4 ng g(-1) dw for SigmaPCDD/Fs,
      11 ng g(-1) dw for SigmaPCB, 3 ng g(-1) dw for SigmaDL-PCBs and 5.1 ng g(-1) dw
      for SigmaPBDEs. Similar PCDD/F and DL-PCB congener patterns in all the
      environmental compartments of LM point to an important, if not dominant,
      contribution of atmospheric deposition as source of these pollutants into LM. In
      contrast, PBDE congener distribution was not similar in the different
      environmental compartments. BDE 47 dominated air and settling material, while BDE
      209 was the predominant congener in the bulk atmospheric deposition. Moreover,
      sediments showed two distinct PBDE congener profiles. Lower PBDE concentrated
      sediments were dominated by congeners 47 and 99, while BDE 209 dominated in
      higher PBDE concentrated samples. This suggests the influence of local sources as
      well as atmospheric input of PBDEs into LM.

PMID- 17554432
TI  - Real-time PCR for detection of the Aspergillus genus.
AB  - Aspergillus is a genus of mold that has strong indoor sources, including several
      species capable of acting as opportunistic pathogens. Previous studies suggest
      that Aspergillus could serve as an indicator for abnormal mold growth or
      moisture, making it an important genus for environmental monitoring. Here, a
      quantitative polymerase chain reaction (qPCR, or real-time PCR) assay is
      presented for Aspergillus. The assay shows good specificity for the genus,
      detecting all Aspergillus species tested, although a few non-Aspergillus species
      are also amplified. Sensitivity testing demonstrates that DNA representing one
      conidium can be detected. A validation study compared qPCR results against direct
      microscopy counts using A. fumigatus conidia aerosolized into a laboratory
      chamber. The assay was then used to quantify Aspergillus in indoor air samples,
      demonstrating its utility for environmental monitoring. Analysis of a small
      number of clinical sputum samples showed complete agreement with culturing
      results.

PMID- 17554433
TI  - Field comparison of passive samplers versus UV-photometric analyser to measure
      surface ozone in a Mediterranean area.
AB  - The aim of the present work is to compare the performance of the Radiello passive
      sampler versus UV-photometric ozone analyser to measure surface ozone in a
      Mediterranean Spanish coastal area. The comparison presented considers precision,
      bias, accuracy, selectivity, detection limit, cost and applicability. For
      assessing precision, co-located samplers were exposed in duplicate in two
      reference-sampling sites, beside UV-photometric ozone analyser. Bias was
      calculated comparing results of passive samplers exposed in three reference
      sampling sites and two contrast-sampling sites with the measurements given by the
      reference analysers. Accuracy was calculated following the EN 482:1994 standard.
      The limit of detection was calculated as 3 times the standard deviation of the
      blanks in a batch of passive samplers. The compared Radiello passive samplers
      give a precision of 5.2%, a bias of 13.8%, an accuracy of 20.5% and a limit of
      detection of 12.6 microg m(-3). The selectivity and applicability of this
      methodology is in both aspects successful. Surface ozone levels measured with
      passive samplers were comparable with the averaged values measured with the
      reference analyser both in the reference-sampling sites and in the contrast
      sampling sites.

PMID- 17554435
TI  - [The plague].

PMID- 17554434
TI  - Measurement of organic contaminants and biological effects in Scottish waters
      between 1999 and 2005.
AB  - Concentrations of organic contaminants were determined in sediment and fish
      collected annually at six sites around Scotland between 1999 and 2005, as part of
      the UK National Marine Monitoring Programme. Polycyclic aromatic hydrocarbons
      (PAHs) and chlorobiphenyls (CBs) were measured in sediment, while CBs and
      ethoxyresorufin-O-deethylase (EROD) activities were measured in the fish. Highest
      PAH concentrations in sediment were found at sites where higher coastal
      influences would be expected (e.g., Clyde and Solway) and four of the six sites
      gave PAH concentrations above OSPAR background assessment concentrations (BACs).
      A significant downward trend in the median total PAH concentrations, normalised
      to total organic carbon (TOC), was found at one of the six sites (Minches). The
      PAH profiles at all sites were consistent over the 6 year period, indicating that
      the sites are relatively stable and PAH sources are not changing. There was an
      indication of a greater petrogenic input on the west coast, with sediment from
      the Clyde, Solway and Minches having a greater proportion of 2- and 3-ring PAHs
      and a lower proportion of 5-ring PAHs. CB concentrations at all sites were low
      compared with UK estuarine sites and similar to sediment from more remote areas:
      however, BACs were exceeded. No significant trends were detected in either the
      sediment CB concentrations or patterns at any of the six sites. CB concentrations
      were significantly higher in fish liver collected from the Clyde. Concentrations
      at the other five sites were low, with the majority of samples having
      concentrations for the ICES7 CBs of <500 microg kg(-1) lipid weight. However,
      individual CB concentrations were still above the BACs. Hepatic EROD activities
      were measured in male plaice from 2002-2005 and were generally low (<10 pmol min(
      1) mg protein(-1)). No temporal trends were detected in either CB concentrations
      or the EROD activity.

PMID- 17554436
TI  - [Clinical and serological evidence of canine rickettsiosis in Chile].
AB  - Rickettsial infections in pets have not been documented in Chile. Some of those
      infections have relevant zoonotic potential. OBJECTIVES: To report two
      serologically confirmed cases of canine rickettsiosis. To determine
      seroprevalence to Rickettsia sp in a group of dogs. METHODS: IgG antibodies anti
      R. conorii and anti-A. phagocitophilum by IFI in two dogs with clinical
      rickettsiosis. IgG antibodies anti-R. conorii in a group of 77 dogs. RESULTS: 
      CLINICAL CASES: a dog presented with fever, myalgias and melena, another dog with
      bleeding and neurological involvement. Seroprevalence: 35% of the dogs had
      antibodies against Rickettsia. DISCUSSION: This is the first evidence of canine
      rickettsiosis in Chile, both clinical and serological. Co-infection with two
      tickborne agents: Rickettsia and Anaplasma, is documented. Molecular studies are
      needed to confirm the rickettsial species present in Chile. The zoonotic role of
      these infections must be also studied.

PMID- 17554437
TI  - [Nasal carriage of Staphylococcus aureus in a cohort of children with cancer].
AB  - According to medical literature, nasal carriage of Staphylococcus aureus in
      pediatric age in the general population ranges between 10 and 40 %, not being
      clearly established in children with cancer. In order to determine the prevalence
      in this group and its possible increment through successive hospitalizations, we
      studied the Calvo Mackennas oncologic patients below 19 years of age, with a
      series of nasal cultures. We took four samples for each patient in a period of
      one year. Of 80 patients initially included, 10 died, 9 returned to their city of
      origin before the end of the study and in 8 cases it was not possible to complete
      the follow-up. Prevalence of nasal carriage was 21.2% (17/80). From 17 children
      colonized, 14 lost this condition, 2 abandoned the follow-up and only 1 was
      positive at the end of the study. Incidence of hospitalization due to febrile
      neutropenia was 28.7% (23/80) and the relation between nasal carriage and the
      number of these events was not significant (p = 0.59). The relation between the
      number of hospitalizations and an increment in nasal colonization (p = 0,80) was
      also not significant. In conclusion, nasal carriage of Staphylococcus aureus in
      children with cancer is similar to carriage described for healthy children.
      Carriage would be a transitory condition, variable through time for each patient,
      without relation to a greater number of febrile neutropenia episodes.

PMID- 17554438
TI  - [Detection of some zoonotic agents in the domestic pigeon (Columba livia) in the
      city of Chillan, Chile].
AB  - INTRODUCTION: There is an increase in the population of doves (Columba livia) as
      well as their contact with healthy and immunocompromised hosts. OBJECTIVES:
      detection of some zoonotic agents of the domestic pigeon (Columba livia) in
      Chillan city, Chile. MATERIALS AND METHODS: From October 2002 to September 2003,
      100 domestic pigeons were captured. Blood, organs and intestine contents were
      sampled from each pigeon. The samples were cultivated in different kinds of agar
      according to the searched microorganism. Fungi were typified by morphological
      studies after staining with 2% methylene blue. For the detection of Chlamydophila
      psittaci a commercial Elisa kit (IDEXX) was used. RESULTS: Pigeons were
      registered positive for: chlamydiosis (11%), staphylococcus (8%), salmonellosis
      (4%) and aspergillosis (1%). No pigeon had evidence of cryptococcosis and
      listeriosis. CONCLUSIONS: these results confirm that domestic pigeon could act as
      vector of zoonotic agents of public health importance.

PMID- 17554439
TI  - [Isolation and identification of species from the genera Aeromonas, Vibrio, and
      Plesiomonas from extraintestinal samples in Cuba].
AB  - Extraintestinal infections caused by the genera Aeromonas, Vibrio and Plesiomonas
      have high morbidity and mortality rates in different areas of world. From January
      2002 to December 2003, the National Reference Laboratory for Acute Diarrhoeal
      Diseases of the Pedro Kouri Tropical Medicine Institute received 95 gram
      negative, facultative anaerobic, oxidase positive bacilli strains from different
      extraintestinal specimen (blood, ear exudates, infected wounds, conjunctive
      exudates, urine, and catheters, among others) sent by different provincial
      laboratories along the country. Aeromonas caviae, Aeromonas veronii bv sobria,
      Aeromonas jandaei, Vibrio cholerae no-O1, Vibrio vulnificus, Vibrio fluvialis and
      Plesiomonas shigelloides were the species most frequently found in the sample
      analysed.

PMID- 17554440
TI  - [Diagnosis and treatment of human papilloma virus].
AB  - The identification and treatment of human papillomavirus (HPV) infections and HPV
      associated neoplasm are complex. Difficulties in diagnosis and treatment of HPV
      associated diseases arise from inabilities to detect HPV efficiently, the lack of
      specific antiviral drugs active against HPV and the high rates of recurrence and
      persistence of HPV infections after treatment. We present a review of therapies
      for HPV infections.

PMID- 17554441
TI  - [Recurrent oral ulcer: clinical characteristic and differential diagnosis].
AB  - Recurrent aphthous stomatitis (RAS), are common inflammatory lesions of the oral
      mucous, usually round or ovoid, circumscribed by erythematous haloes with a
      yellow-grey floor and mostly painful. The RAS has reached an incidence about 20%
      in general population, present on any aged group, especially adolescents and
      young adults. Etiopathogenesis of RAS is not entirely understood. Some factors
      involved include immune system anomalies, infections, nutritional deficiency,
      mucous traumatism, food or contact allergy, autoimmunity illness and cancer;
      together with psychiatric, genetic and environment agents. In this article, main
      clinical features, etiology related factors, differential diagnosis and initial
      study of patients consulting for RAS are presented.

PMID- 17554442
TI  - [Leptospirosis: a literature review].
AB  - We review epidemiological, clinical, laboratory and therapeutic aspects of
      leptospirosis. In relation to the epidemiology it is worth noting the importance
      of recreational and occupational risk factors, as well as the lack of data
      available in Chile before the year 2000, when leptospirosis became the object of
      epidemiological surveillance. There are many forms of clinical presentations for
      this disease and often signs and symptoms may be nonspecific. Thus, differential
      diagnosis must include many clinical entities. Laboratory diagnosis, on the other
      hand, is complex and not widely available. Although still controversial, a
      literature review supports antimicrobial treatment, with different antibiotics to
      choose from.

PMID- 17554443
TI  - [Influenza: immunization to new age groups].
AB  - Influenza immunization is a main tool to prevent this important viral illness.
      Traditional vaccine recommendations, mainly focused to elderly and people with
      chronic medical conditions, have been expanded during last years. The article
      summarizes the fundament of lowering the age cut off in adults and of the
      incorporation of healthy infants between 6 and 24 months. The performance of the
      vaccine in those new age groups is analyzed. Finally, new groups to possibly be
      incorporated in future vaccine recommendations are mentioned.

PMID- 17554444
TI  - [Enterococcus sp., part 1].

PMID- 17554445
TI  - [Actinomycotic infective endocarditis of the mitral valve. Anatomoclinical case
      and review of literature].
AB  - Actinomycotic infections of the heart is an uncommon disease, especially if the
      infection affects the valvular endocardium as primary focus. Just a few cases
      have been reported previously. We report a case of primary endocarditis of the
      mitral valve caused by Actinomyces sp diagnosed at necropsy in a 34 year-old man
      with history of chronic rheumatic disease presenting as a usual case of infective
      endocarditis.

PMID- 17554446
TI  - [Snake bite by Philodryas chamissonis. A case presentation and literature
      review].
AB  - There are two species of snakes associated with snake bite poisoning in Chile:
      Philodryas chamissonis and Tachymenis peruviana. A case associated with a P.
      chamissonis bite occurring during a summer activity in San Antonio, V Region, is
      presented. The bite compromised the dorsum of the right hand between the thumb
      and the index finger and was initially painless. During the following 24 hours
      equimotic edema developed up to the shoulder and pectoral region, with intense
      pain, headache, nausea, fever and appearance of a serohematic bulla on the elbow
      fold. The patient was treated with antihistamines, systemic steroids, analgesia
      and antibiotics for 7 days. Other cases of snake bites published in Chile are
      reviewed and treatment and prevention strategies are proposed.

PMID- 17554447
TI  - [Notes about the history of poliomyelitis in Chile].

PMID- 17554448
TI  - [Honesty and good faith: two cornerstones in the ethics of biomedical
      publications].
AB  - The editors of medical journals should take the steps necessary to assure its
      readers that the contents of their publications are based in true data, that they
      are original and fulfill the ethical rules of biomedical and clinical research,
      including its reporting. This editors role has become increasingly difficult
      since the pressure to publish scientific papers is progressively stimulated by
      the role that those papers play in curricula vitae when the authors apply for
      university positions, academic promotions, research grants and for their personal
      prestige. As a consequence, increasing instances of misconduct in scientific
      publications are detected. Some cases are noticed during the editorial process,
      mostly when peer reviewers identify redundant publications or plagiarism. Other
      cases are denounced after a manuscript was published. It is the editors duty to
      verify the misconduct, request an explanation from the authors and, if their
      answer is unsatisfactory, report the problem to the institutional authorities
      supporting the authors. The editors should denounce the situation in a
      forthcoming issue of the journal. Universities should enforce the teaching of
      ethical rules that govern the report of scientific information. Revista Medica de
      Chile follows recommendations given by the International Committee of Medical
      Journal Editors, the World Association of Medical Editors and other groups, but
      honesty and good faith in all the actors involved in the process of biomedical
      publications (authors, reviewers, editors) remain the cornerstones of scientific
      good behavior.

PMID- 17554449
TI  - [Post suckling prolactin and estradiol levels as predictors of the time of
      appearance of the first post partum menstruation].
AB  - BACKGROUND: The variability in the duration of lactational amenorrhoea (LA) lead
      to develop statistical multivariate models to predict the risk of the appearance
      of the first postpartum menstruation. AIM: To estimate the probability of
      recovering the first postpartum menstruation by means of a survival analysis,
      including hormonal levels and other parameters as predictor variables. MATERIAL
      AND METHODS: Eighty one mothers in exclusive breastfeeding until the sixth
      postpartum month, in whom estradiol, basal and post suckling prolactin were
      measured at the third post partum month, were studied. The variables that better
      predict the appearance of the first menstruation between the 3rd and 12th
      postpartum months, were identified using a Cox model survival analysis. RESULTS:
      The median amenorrhea survival time (the lapse when the chance of recovering
      menstruation is 50%) was 209 days from delivery. Dichotomized estradiol and post
      suckling prolactin were the only significant variables that predicted the return
      of menstruation, with cutoff points of 190 pmol/ and 2,550 mIU/L, respectively.
      CONCLUSIONS: Post suckling prolantin and estradiol levels, measured at the third
      post partum month, are predictors for the time of appearance of the first
      postpartum menstruation.

PMID- 17554450
TI  - [Treatment results of early breast cancer: a retrospective review].
AB  - BACKGROUND: Breast cancer will develop in one out of ten women during their
      lifetime. Early diagnosis has increased in recent years. AIM: To describe a
      population of women with breast cancer stage T1N0M0. To analyze radiation therapy
      toxicity and to evaluate treatment results. MATERIAL AND METHODS: Retrospective
      review of the medical records of 125 women (aged 35 to 80 years) with breast
      cancer T1N0M0, that were treated between January 1997 and May 2004, with breast
      conserving surgery and postoperative radiation therapy at an oncology center.
      Patients lost from follow up were contacted by telephone. RESULTS: An abnormal
      screening mammography was the reason for consult in 62% of cases. The average
      tumor size was 11.6 mm. Tumors detected with screening mammogram were smaller
      than those detected on physical exam. The most common radiotherapy toxicity was
      erithema, which was severe in 2.5% of cases. No patient had to stop the radiation
      treatment due to toxicity. One patient developed arm edema. Tamoxifen was
      prescribed for 5 years to 80% of patients and 17 patients received chemotherapy.
      After an average follow up of 40 months, no patient has developed local breast
      relapse, three patients developed contralateral breast cancer and three developed
      distant metastasis. Two patients died from breast cancer. Disease free survival
      was 95%. CONCLUSIONS: Radiotherapy was well tolerated and had excellent local
      control. Screening mammography detects small tumors. Survival is excellent for
      early stage breast cancer.

PMID- 17554451
TI  - [Under diagnosis of fetal growth restriction by the new growth curves of the
      Chilean Ministry of Health].
AB  - BACKGROUND: Fetal growth restriction (FGR) is associated with increased risk of
      perinatal morbidity or death. Nationwide implementation of new fetal growth
      charts, requires a lower fetal weight for the diagnosis of FGR, compared to
      previous ones. This may lead to an under diagnosis of FGR in a large proportion
      of neonates. AIM: To compare the morbidity, mortality and anthropometry of
      neonates with FGR, diagnosed by MINSAL and Juez curves, with normal weight
      newborns in the same period (2000-2004). MATERIAL AND METHODS: Revision of
      medical records of all births occurring in a maternity hospital between 2000 and
      2004. The number of neonatal deaths, and the presence of hyperbilirubinemia,
      polyglobulia, hypoglycemia and hypothermia, were compared among children
      classified to be below percentile 10 of fetal growth according to both growth
      charts. RESULTS: FGR was diagnosed in 4,4% (502/11.289) and 9% (1.029/11.289) of
      newborns by MINSAL and Juez curves respectively. Compared to normal weight
      controls, the 527 newborns without FGR according to MINSAL curves, but below
      percentile 10 of Juez curves, had an odds ratio (OR) for polyglobulina of 8.14
      (95% confidence intervals (CI): 1.01-65.34), an OR for neonatal hypoglycemia of
      5.10 (95% CI: 1.11-23.39) and an OR for a ponderal index below 10th percentile of
      10.98 (95% CI: 6.84-17.64). CONCLUSIONS: Newborns without a diagnosis of FGR by
      MINSAL curves but below 10th percentile by Juez curves, have neonatal outcomes
      suggesting a true FGR. Juez curves should be maintained as a standard for the
      evaluation of fetal growth in our population.

PMID- 17554452
TI  - [Seroprevalence of IgG antibodies against parvovirus B19 among blood donors from
      Santiago, Chile].
AB  - BACKGROUND: Parvovirus B19 (B19) is associated with a wide range of disease
      manifestations, whose severity depends on the immunological and hematological
      status of the host. Infection with B19 has been reported worldwide and the
      prevalence of immunoglobulin G antibodies against B19 increases with age and
      varies by location and time of the last B19 epidemic. AIM: To evaluate the
      prevalence of IgG antibodies against Parvavirus B19 virus in a population of
      volunteer blood donors at two hospital blood banks in Santiago, Chile. MATERIAL
      AND METHODS: A total of 400 serum samples from blood donors aged 18 to 65 years,
      were examined for the presence of IgG antibodies against Parvovirus B19. RESULTS:
      The overall prevalence of IgG antibodies was 54.8%. No significant difference was
      found between men and women (57.6% and 49.3%, respectively). CONCLUSIONS: IgG
      antibody seroprevalence against Parvovirus B19, was 55% in this sample of Chilean
      blood donors. This figure is in agreement with previous reports from abroad.

PMID- 17554453
TI  - [A gender comparison of legal and illicit drug consumption].
AB  - BACKGROUND: It is possible that men consume a higher amount of legal and illegal
      drugs than women. This can be assessed using the peer methodology, that is an
      adaptation of the privileged access interviewers (PAI) method and allows to
      identify populations in which there may be a tendency to under state a phenomenon
      (hidden populations) AIM: To compare the consumption of legal and illegal drugs
      by gender. MATERIAL AND METHODS: Drug consumption was assessed using a peer
      methodology in university students between 18 and 26 years of age. RESULTS: A
      random sample of 56 women (mean age 21.6 years) and 86 men (mean age 21.5 years),
      was studied. Women tended to report a higher proportion of tobacco consumption
      than men. Both genders had a similar consumption behavior of alcohol, total legal
      drugs, marihuana, cocaine, ecstasies and total illegal drugs. Among subjects that
      recognized the consumption of legal drugs, men have a higher proportion of
      illicit drug use and women have a higher proportion of smoking. Men have a higher
      awareness of the damages caused by drug consumption. CONCLUSIONS: The results in
      these small population sample do not support the hypothesis that men have a
      higher frequency and proportion of illicit drug consumption.

PMID- 17554454
TI  - [Teenager counselling in primary care].
AB  - BACKGROUND: Teenager counseling to recognize risks and reinforce strengths is
      carried out in a primary care outpatient clinic since 2003. AIM: To describe the
      epidemiology and causes for consultation in this teenage counseling program.
      MATERIAL AND METHODS: Retrospective review of the records of 116 teenagers
      (median age 13 years, 67% females) that received teenager counseling. RESULTS:
      Seventy percent of women and 50% of men came from nuclear families. More than two
      thirds were primogenital. Most adolescents were accompanied by their mother, that
      were the main adult raw model. Fifty percent had dysfunctional families. All were
      attending school regularly and 21% of women and 29% of men had repeated a school
      level. Sixty eight percent of women and 62% of men declared to have a life
      project. Twenty percent were worried about their physical appearance. Seventy
      seven percent of women and 62% of men considered themselves as happy. Thirty six
      percent of women and 14% of men smoked. The figures for alcohol consumption were
      21% and 14%, respectively. The causes for consultation were obesity, overweight,
      unspecific symptoms, behavioral problems, bad school achievement, communication
      problems or pregnancy. Reasons for counseling were family dysfunction, low self
      esteem, bad school achievement and information about sexuality. CONCLUSIONS: The
      information obtained could help to improve the interdisciplinary work and to
      coordinate counseling with the family and schools.

PMID- 17554455
TI  - [Laparoscopic Heller myotomy for esophageal achalasia].
AB  - BACKGROUND: Achalasia is characterized by an incomplete relaxation of the lower
      esophageal sphincter. The best treatment is surgical and the laparoscopic
      approach may have good results. AIM: To assess the results of laparoscopic Heller
      myotomy among patients with achalasia. MATERIAL AND METHODS: Prospective study of
      patients subjected to a laparoscopic Heller myotomy between 1995 and 2004.
      Clinical features, early and late operative results were assessed. RESULTS:
      Twenty seven patients aged 12 to 74 years (12 females) were operated. All had
      disphagia lasting for a mean of 32 months. Mean lower esophageal sphincter
      pressure ranged from 18 to 85 mmHg. Eight patients received other treatments
      prior to surgery but symptoms persisted or reappeared. The preoperative clinical
      score was 7. No patient died and no procedure had to be converted to open
      surgery. In a follow up of 21 to 131 months, all patients are satisfied with the
      surgical results and the postoperative clinical score is 1. Only one patient with
      a mega esophagus maintained a clinical score of six. CONCLUSIONS: In this series
      of patients, laparoscopic Heller myotomy was an effective and safe treatment for
      esophageal achalasia.

PMID- 17554456
TI  - [Disclosure of financial sources and conflicts of interest among research
      articles published in Revista Medica de Chile].
AB  - BACKGROUND: Financial relationships between the industry and researchers have
      raised concerns about the existence of conflicts of interest that could influence
      the scientific validity of the studies. AIM: To determine the financial sources
      of research articles published in the Revista Medica de Chile during a five-year
      period. MATERIAL AND METHODS: Retrospective analysis of all articles classified
      as research articles, published in this journal between years 2001-2005,
      identifying the funding source and the existence of a declaration of conflicts of
      interest by the authors. RESULTS: Two hundred seventeen out of 519 research
      articles published in the period (42%) had an explicit financial source
      disclosed. Of these, 28% were funded by internal sources, 36% by Fondo Nacional
      de Desarrollo Cientifico y Tecnologico and 36% by other sources. Twenty-six
      studies (5%) received funding from the industry. In only five of these, the
      authors explicity declared the absence of conflict of interest. Among the studies
      that did not disclose any financial source, one third required some funding to be
      carried out. CONCLUSIONS: Forty two percent of research articles published in the
      last five years did not specify the financial source. Those that did specify a
      funding source were mainly supported by non-profit agencies including university
      centers and governmental funds. This is in contrast with international reports
      that evidence an important financial support from the industry. Only a minority
      of the authors sponsored by the industry declared absence of conflict of
      interest.

PMID- 17554457
TI  - [Impact factor of Latin American medical journals].
AB  - BACKGROUND: Latin American medical journals have a low impact factor. Higher
      quality articles originated in Latin American countries are published in North
      American or European journals. AIM: To analyze the impact factor of Latin
      American journals according to the language of publication. MATERIAL AND METHODS:
      The data base of periodic journals of the Thomson ISI (Journal of Citation
      Report) in the year 2004 was used for the analysis. Four countries with more than
      one journal in the data base of the Thomson ISI were included (Argentina, Brazil,
      Chile and Mexico). RESULTS: Few Latin-American journals are included in the
      Thomson ISI data base. The mean impact factor was 0.76 (0.23-3.2) for eight
      Mexican journals, 0.66 (0.10-2.1) for eight Chilean journals, 0.39 (0.06-0.7) for
      five Argentinian journals and 0.41 (0.09-1.1) for 16 Brazilian journals. The mean
      impact factor for 11 journals written in English was 0.74 (0.12-2.1), 0.53 (0.09
      3.2) for 18 bilingual journals and 0.28 (0.06-0.56) for eight journals written in
      native language. The differences between countries and languages were not
      statistically significant. CONCLUSIONS: The journal impact factor was similar in
      the four countries studied. A non-significant higher impact factor was observed
      in Latin-American journals published in English.

PMID- 17554459
TI  - [Thiazide induced acute pulmonary edema: report of one case].
AB  - Acute pulmonary edema caused by thiazides is uncommon and of difficult diagnosis.
      It is considered an idiosyncratic reaction and the physiopathology or cardiac
      function changes are not well known. We report a 60 year-old female with a
      thiazide induced acute pulmonary edema who was followed with serial measurements
      of type B n-terminal natriuretic peptide fraction as marker for cardiac
      dysfunction. There was a significant elevation of the peptide, not associated to
      evidences of ventricular dysfunction. Its normalization paralleled the resolution
      of the clinical picture.

PMID- 17554458
TI  - [Factorial validation of the alcohol expectancy questionnaire (AEQ-III), in
      adults living in Bucaramanga, Colombia].
AB  - BACKGROUND: Alcohol consumption is associated to expectancies of global positive
      behavioral changes, improvement in sexual performance and a higher level
      assertiveness. These issues are evaluated by the Alcohol Expectancy Questionnaire
      (AEQ-III). AIM: To perform a factorial validation of the Alcohol Expectancy
      Questionnaire (AEQ-III). MATERIALS AND METHODS: The questionnaire was applied to
      a representative sample of 601 subjects aged 18 to 60 years (334 males). These
      subjects also answered a socioeconomic questionnaire. The significant variables
      of the questionnaire were selected using an exploratory factorial analysis. Based
      on the selected variables, the verification was performed using multiple models
      of structural equations. Four factors, namely decrease in physical tension,
      decrease in psychological tension, increase in expressivity and sexuality and
      inhibition and feelings of power, were identified as significant. RESULTS: The
      factorial solution explains 59% of the variance. All the factors are conceptually
      and statistically consistent, with a Cronbach alpha ranging between 0.75 and
      0.83. The global internal consistency was of 0.85. Pearson correlation
      coefficient among factors ranged between 0.45 and 0.74. There was a significant
      difference among socioeconomic levels for the factors lack of inhibition and
      feelings of power and decrease of psychological tension. Goodness of fit
      statistics and parsimony were high, ranging from 0.80 to 0.93. CONCLUSIONS: The
      expectancy decrease of physical tension and decrease of psychological tension are
      a part of individual behavior and could predict problem drinking. The factors
      increase of expressiveness and sexuality and lack of inhibition and feelings of
      power, are more associated to group behaviors.

PMID- 17554460
TI  - [Percutaneous puncture and drainage previous to elective surgical resection of a
      pheochromocytoma presenting as a retroperitoneal abscess: report of one case].
AB  - We report a 57 year-old woman with a big partially cystic adrenal
      pheochromocytoma presenting with high fever and abdominal pain. Based on CT scan
      images and before knowing urinary catecholamines level, the diagnosis of sepsis
      secondary to an abscessed adrenal macrotumor was done. A diagnostic percutaneous
      fine-needle puncture and aspiration was done and antibiotic therapy was started.
      One week later an open surgical drainage and installation of percutaneous
      drainage tubes was carried out. Both procedures were uneventful and the patient
      improved dramatically. Three months later a definitive excision surgery was done.
      After 14 months of follow up, the patient is in excellent conditions and her
      abdominal CT scan is normal.

PMID- 17554461
TI  - [Recurrence of differentiated thyroid carcinoma without concomitant elevation of
      serum thyroglobulin: report of two cases].
AB  - Thyroid carcinoma is the most prevalent endocrine tumor, and the papillary
      carcinoma (PC) is the most common histological type. In the follow-up, after
      thyroidectomy serum thyroglobulin (s-Tg) is used as a marker to evaluate
      recurrence of thyroid carcinoma. In most cases, this parameter allows an adequate
      diagnosis, but occasionally s-Tg may miss the detection of a recurrence. We
      report a 57 year-old female and a 36 year-old male subjected to a total
      thyroidectomy for a papillary thyroid carcinoma with intermediate and high-risk
      of recurrence. Both had a cervical recurrence without a concomitant increase in s
      Tg levels. In both, Tg staining was positive in the tumor cells. These cases
      confirm that in these patients, the follow-up must be done with measurement of s
      Tg and complementary diagnostic tests.

PMID- 17554462
TI  - [Laparoscopic gastrectomy in gastric cancer: experience in four patients].
AB  - BACKGROUND: The development of the laparoscopic surgery has allowed its
      incorporation to the surgical treatment of gastric cancer. AIM: To evaluate the
      feasibility and safety of laparoscopic gastrectomy in gastric cancer in our
      institution. PATIENTS AND METHODS: Prospective data in four patients who
      underwent laparoscopic gastrectomy for gastric cancer from May to August of 2005
      was reviewed. Demographic data, clinical characteristics and postoperative
      results were registered. Patients were staged according to TNM-AJJC staging
      system. RESULTS: Four patients aged 48 to 80 years (three males), underwent a
      completely laparoscopic R0 gastrectomy with lymph node dissection. Two patients
      underwent total gastrectomy. A subtotal Billroth II gastrectomy was performed in
      the other two patients. The mean operative time was 260 minutes (Range 180-330).
      There were no conversions to open surgery. The mean postoperative hospital stay
      was 6.5 days (Range 6-7 days). There were no complications. According to
      pathology, one patient presented carcinoma in stage IA, two patients in stage IB
      and one patient in stage IIIB. The mean number of lymph nodes dissected was 40
      (Range 35-54). CONCLUSIONS: Laparoscopic gastrectomy is a feasible procedure with
      good postoperative results in this preliminary experience.

PMID- 17554463
TI  - [Predictive value of history and physical examination for the diagnosis of
      community-acquired pneumonia in adults: a literature review].
AB  - Distinguishing pneumonia from other causes of respiratory illnesses, such as
      bronchitis, influenza and upper respiratory tract infections, has important
      therapeutic and prognostic implications. This decision is usually made by
      clinical assessment alone or by performing a chest x-ray. The reference standard
      for diagnosing pneumonia is chest radiography, but many physicians rely on
      history and physical examination to diagnose or exclude this disease. A review of
      published studies of patients suspected of having pneumonia reveals that there
      are no individual clinical findings, or combination of findings, that can predict
      with certainty the diagnosis of pneumonia. Prediction rules have been recommended
      to guide the order of diagnostic tests, to maximize their clinical utility. Thus,
      some studies have shown that the absence of any vital sign abnormalities or any
      abnormalities on chest auscultation substantially reduces the likelihood of
      pneumonia to a point where further diagnostic evaluation may be unnecessary. This
      article reviews the literature on the appropriate use of the history and physical
      examination in diagnose community-acquired pneumonia.

PMID- 17554464
TI  - [Ethics in articles published in medical journals].
AB  - Authors of clinical articles have similar motivations and rules than authors in
      other scientific fields. In addition, medical research must obey specific ethical
      rules that apply to studies involving human subjects, including biological
      samples, tissues, cellular or sub cellular samples obtained from them. When
      submitting their reports for publication, authors must declare that they have
      followed such ethical rules and also should declare any possible conflict of
      interest that may have arisen. External peer reviewers and the editors should
      also conform to limitations by eventual conflicts of interest. Authors should
      respect specific ethical norms that apply to the process of submitting,
      publishing and reproducing their manuscripts. In recent years, the editors of
      Revista Medica de Chile have become aware of five instances of misconduct
      committed by authors of articles submitted or already published. Four correspond
      to redundant publications and one exhibits overt plagiarism in the text and
      syntax. Appropriate actions have been taken following recommendations published
      by the International Committee of Medical Journal Editors, the World Association
      of Medical Editors and other groups. The present article stresses that authors
      and their sponsoring institutions must be aware of the importance of following
      ethical rules when reporting scientific work.

PMID- 17554465
TI  - [The diagnostic process].

PMID- 17554467
TI  - Postpartum anal sphincter lacerations in a population with minimal exposure to
      episiotomy and operative vaginal delivery.
AB  - This case-control study was designed to identify risk factors for anal sphincter
      lacerations (ASL) in a multicultural population where episiotomies and operative
      vaginal deliveries are rarely performed. Cases were subjects with ASL delivered
      between July 1997 and June 2003. Two controls were selected for each case matched
      for gestational age. Independent variables collected included age,
      race/ethnicity, parity, tobacco use, medical conditions, episiotomy, operative
      vaginal delivery, epidural use, and infant weight. One thousand and sixty-six
      subjects met the inclusion criteria. The risk of ASL increased with increasing
      maternal age (Odds ratio [OR] 1.09 per year, 95% confidence interval [CI] 1.06,
      1.12) and increasing infant weight (OR 1.09 per 100 g, 95% CI 1.06, 1.13).
      Multiparity was protective (P1 vs P2 OR 0.19, 95% CI 0.13, 0.28, and > or =P3 vs
      P1 OR 0.04, 95% CI 0.02, 0.11). Hispanic and Native American women were at
      increased risk for ASL (OR 2.08, 95% CI 1.41, 3.09 and OR 1.92, 95% CI 1.07,
      3.45, respectively).

PMID- 17554468
TI  - Degradation kinetics of caffeine and related methylxanthines by induced cells of
      Pseudomonas sp.
AB  - In this study, the kinetics of degradation of caffeine and related
      methylxanthines by induced cells of Pseudomonas sp. was performed. The kinetics
      data showed that degradation of caffeine, theobromine, and 7-methylxanthine
      followed Michealis-Menten kinetics. The values of K (m) are low for caffeine and
      7-methylxanthine and high for theobromine. Degradation of caffeine and
      theobromine was enhanced in the presence of NADH and NADPH, whereas the
      degradation of 7-methylxanthine was unaffected. Among the various metal ions
      tested, Fe(2+) was found to enhance the rate of degradation for all three
      substrates, whereas Zn(2+) and Cu(2+) inhibited the degradation of caffeine and
      theobromine but not 7-methylxanthine. The differences in kinetic parameters and
      cofactor requirement suggest the possibility of the involvement of more than one
      N-demethylases in the caffeine catabolic pathway in Pseudomonas sp. The induced
      cells can serve as effective biocatalysts for the development of
      biodecaffeination techniques.

PMID- 17554469
TI  - Genotypic and phenotypic profiles of enterotoxigenic Escherichia coli associated
      with acute diarrhea in Tunis, Tunisia.
AB  - No past studies of acute diarrhea in Tunisia have examined the phenotypic and
      genotypic profiles of enterotoxigenic Escherichia coli (ETEC) isolates. We
      determined 65 ETEC isolates derived from a total of 327 E. coli isolates
      collected from a previous study (acute diarrheal and healthy persons, children
      and adults n = 214) and 32 E. coli isolates derived from an acute diarrheal
      outbreak in Kabaria-Ennour city, Tunis. All E. coli isolates were screened by
      polymerase chain reaction (PCR) for ETEC virulence genes: sta (heat-stable toxin
      gene) and elt (heat-labile toxin gene). Seventy-two percent (47 of 65) of ETEC
      strains expressed the sta gene only, 21.5% (14 of 65) expressed the elt gene and
      6.1% (4 of 65) expressed both genes. For the outbreak isolates, the elt gene was
      predominant (10 isolates out of 14). Ganylioside GM1 enzyme-linked immunosorbent
      assay (GM1-ELISA) was used to validate the PCR results and this was confirmed by
      dot blot assay. The same results were obtained. The most common colonization
      factors (CFs) were CFA/I (44.6%) and coli surface antigen 6 (CS6) (11%), and
      44.6% of the isolates showed no association with either CFAs. Resistance of ETEC
      isolates to tetracycline (38.5%), streptomycin (26%), and beta-lactam agents
      (ticarcillin 26%, amoxicillin 24.6%, cephalotin 21.5%) was common. Regarding
      serotypes, the majority of ETEC isolates serotyped as O86:H(-) (n = 16), O128:H2
      (n = 11), and O127:H21 (n = 10). Other serotypes found were O111:H(-) (n = 6) and
      O126: H(-) (n = 5). DNA macrorestriction fragment analysis by pulsed-field gel
      electrophoresis (PFGE) using the XbaI enzyme was conducted to investigate the
      epidemiological clonal relationship among ETEC isolates. Major patterns were
      identified among which some of outbreak ETEC isolates belonged. These data
      suggest that a proportion of acute diarrhea in Tunis represents the confluence of
      small epidemics by clonality-related ETEC isolates that are transiently
      introduced or that persist in our community.

PMID- 17554470
TI  - Effects of cations on antimicrobial activity of ostricacins-1 and 2 on E. coli
      O157:H7 and S. aureus 1056MRSA.
AB  - Ostricacin-1 and ostricacin-2 (Osp-1 and Osp-2) were beta-defensins antimicrobial
      peptides that were purified from ostrich leukocytes using a cation-exchange
      column and a semi-prep RP-HPLC column. Both ostricacins were subjected to
      increased concentrations of monovalent cations (K(+) and Na(+)) and divalent
      cations (Ca(2+) and Mg(2+)) in order to investigate the effect of cations on the
      activity of these ostricacins on Gram-negative bacteria and Gram-positive
      bacteria. The radial diffusion assay method showed that both ostricacins were
      sensitive to the presence of cations. The divalent cations showed more
      antagonized effect on the activity against Gram-negative bacteria than the
      monovalent cations, as the ostricacins lost ability to inhibit bacterial growth
      at very low concentration (5 mM). When viewed in the context of other defensins
      activity, our data support a hypothesis that defensins' overall net positive
      charge determine the sensitivity to cations.

PMID- 17554471
TI  - Role of antibiosis in suppression of charcoal rot disease by soybean endophyte
      Paenibacillus sp. HKA-15.
AB  - Four defective (AFM(-)) mutants of Paenibacillus sp. HKA-15 that no longer
      produced the peptide antifungal metabolites were developed through ethyl methane
      sulfonate (EMS) mutagenesis and used for in vivo experimentation. Reduced
      percentage of seed germination by mutants DM1 and DM2 (22.5% and 25%,
      respectively) and a high percent of disease incidence (69.3% and 67%,
      respectively) compared to wild-strain HKA-15 (80% seed germination and 27%
      disease incidence) indirectly indicated the role of peptide metabolite on disease
      suppression. Plants treated with AFM(-) clones showed stunted growth and the
      presence of pepperlike microsclerotia in the stem tissues. Light and scanning
      electron microscopic studies clearly showed the effect of peptide antibiosis on
      hyphal morphology. Exposure to crude extracts of antibiotics produced abnormal
      contraction of fungal cytoplasm, granulation, and fragmentation of hyphal mycelia
      and cell lysis. The presence of bacterial cells in the lumen of degrading fungal
      mycelium suggested a direct involvement of Paenibacillus sp. HKA-15 in the lysis
      of Rhizoctonia bataticola.

PMID- 17554472
TI  - Cervical auscultation synchronized with images from endoscopy swallow
      evaluations.
AB  - Cervical auscultation is the use of a listening device, typically a stethoscope
      in clinical practice, to assess swallow sounds and by some definitions airway
      sounds. Judgments are then made on the normality or degree of impairment of the
      sounds. Listeners interpret the sounds and suggest what might be happening with
      the swallow or causing impairment. A major criticism of cervical auscultation is
      that there is no evidence on what causes the sounds or whether the sounds
      correspond to physiologically important, health-threatening events. We sought to
      determine in healthy volunteers (1) if a definitive set of swallow sounds could
      be identified, (2) the order in which swallow sounds and physiologic events
      occur, and (3) if swallow sounds could be matched to the observed physiologic
      events. Swallow sounds were computer recorded via a Littmann stethoscope from 19
      healthy volunteers (8 males, 11 females, age range = 18-73 years) during
      simultaneous fiberoptic laryngoscopy and respiration monitoring. Six sound
      components could be distinguished but none of these occurred in all swallows.
      There was a wide spread and a large degree of overlap of the timings of swallow
      sounds and physiologic events. No individual sound component was consistently
      associated with a physiologic event, which is a clinically significant finding.
      Comparisons of groups of sounds and events suggest associations between the
      preclick and the onset of apnea; the preclick and the start of epiglottic
      excursion; the click and the epiglottis returning to rest; the click and the end
      of the swallow apnea. There is no evidence of a causal link. The absence of a
      swallow sound in itself is not a definite sign of pathologic swallowing, but a
      repeated abnormal pattern may indicate impairment. At present there is no robust
      evidence that cervical auscultation of swallow sounds should be adopted in
      routine clinical practice. There are no data to support the inclusion of the
      technique into clinical guidelines or management protocols. More evaluation using
      imaging methods such as videofluoroscopy is required before this subjective
      technique is validated for clinical use by those assessing swallowing outside of
      a research context.

PMID- 17554473
TI  - Evaluation of a solid bolus suitable for esophageal scintigraphy.
AB  - This study was designed to select a suitable solid bolus for esophageal
      scintigraphy. Optimally, a bolus should leave minimal residual buccal and
      pharyngeal activity after being swallowed. We compared the oropharyngeal behavior
      of three boluses, i.e., omelette, egg white, and pate of 1- and 3-ml volume.
      Thirty patients without dysfunction of the upper esophageal sphincter were
      recruited for the study. Scintigraphy interpretation was based on the results of
      condensed images and time activity curves. A total of 108 oropharyngeal transits
      were analyzed. First we determined the most appropriate volume (1 or 3 ml) of
      pate, omelette, and egg white (i.e., the volume with the least residual
      oropharyngeal activity). Buccal or pharyngeal bolus retention occurred
      significantly less frequently with 1 ml pate than 3 ml (p = 0.03) and also less
      frequently with 3 ml egg white than with 1 ml egg white (p = 0.03), and the mean
      buccal bolus retention index was lower using 3 ml omelette than 1 ml omelette (p
      = 0.03). Then we identified the most suitable of the three selected boluses. Both
      oral and pharyngeal residues were higher for pate (1 ml) than for omelette (p =
      0.02 and 0.05), and pharyngeal residue was significantly lower for omelette (3
      ml) than for egg white (3 ml) (p = 0.02). In conclusion, a 3-ml bolus of
      radiolabeled omelette seems to be the most suitable bolus for exploration of
      esophageal transit, and its use could enhance the potential of scintigraphy in
      the assessment of esophageal disorders.

PMID- 17554474
TI  - Neurogenesis in the adult brain: is there an association with mental disorders?

PMID- 17554475
TI  - The Tol1 transposable element of the medaka fish moves in human and mouse cells.
AB  - DNA-based transposable elements can be used as tools for gene engineering and
      gene therapy. A great advantage over RNA-mediated elements and retroviruses is
      the simplicity and safety of usage. The Tol1 element of the medaka fish Oryzias
      latipes has structural features of DNA-based elements. Although its excision has
      already been demonstrated, de novo insertion has not been observed, and a
      transposase has not been hitherto identified. We first cloned, through in silico
      search alignments and genomic library screenings, a 4.4-kb Tol1 copy carrying
      open reading frames and then identified, by mRNA analysis, a 2.9-kb transcript
      coding for 851 amino acids. The protein product of this transcript catalyzed
      transposition of a nonautonomous Tol1 copy in human and mouse culture cells. This
      identification of a fully functional Tol1 transposase could lead to the
      development of new tools for basic and translational molecular biology
      applications in mammals.

PMID- 17554476
TI  - Allelic variation in the NPY gene in 14 Indian populations.
AB  - NPY is a 36-aminoacid peptide expressed in several areas of the nervous system.
      Neuropeptide Y (NPY) receptors represent a widely diffused system that is
      involved in the regulation of multiple biological functions. The human NPY gene
      is located in chromosome 7. The functional significance of coding Leu7Pro
      polymorphism in the signal peptide of preproNPY is known. Six hundred and fifty
      four individuals of 14 ethnic Indian populations were screened for three
      mutations in the NPY gene, including Leu7Pro. We found that the Pro7 frequencies
      among the studied populations were much higher than in previous studies from
      other parts of the world. The highest allele frequency of Pro7 was detected in
      the Kota population in the Nilgiri Hill region of south India, and this may
      reflect a founder event in the past or genetic drift. All populations followed
      the Hardy-Weinberg equilibrium for the assayed markers. A total of five
      haplotypes were observed, only two of which were found to occur with a high
      frequency in all populations. No linkage disequilibrium (LD) was observed across
      the tested alleles in any population with the exception of Leu7Pro and Ser50Ser
      in the Badaga population (chi(2) = 13.969; p = 0.0001).

PMID- 17554478
TI  - Elevation of intracellular ca(2+) concentration induced by hypoxia in retinal
      ganglion cells.
AB  - PURPOSE: To analyze the mechanism of hypoxia-induced changes of the intracellular
      Ca(2+) concentration ([Ca(2+)](i)) in retinal ganglion cells (RGCs). METHODS:
      Fluo-3 was applied to the cut edge of the optic nerve of 6-week-old rats. The
      retina was sliced, and the Ca images were captured. A hypoxic condition was
      created by superfusing the retinal slice with an oxygen/glucose-deprived
      solution. RESULTS: The retrograde staining method filled the RGCs selectively.
      Fifteen minutes of hypoxic conditions induced an increase in [Ca(2+)](i) in the
      RGCs (Delta0.13 +/- 0.03, n = 23). Application of 60 microM DL-2-amino-5
      phosphonovaleric acid partially blocked the hypoxia-induced [Ca(2+)](i) increase
      in dendrites (Delta0.03 +/- 0.02, n = 4, P < 0.05) but not in the somata
      (Delta0.12 +/- 0.02, n = 9). The RGC dendrites showed a further increase in
      [Ca(2+)](i) after being switched back to an oxygenated solution (Delta0.14 +/-
      0.04, n = 4). Neither 6-cyano-7-nitroquinoxaline-2,3-dione disodium, DL: -threo
      beta-benzyloxyaspartate, nifedipine, nor bepridil inhibited the hypoxia-induced
      [Ca(2+)](i) increase. A Ca(2+)-free superfusion prevented the hypoxia-induced
      [Ca(2+)](i) increase in the somata (Delta0.07 +/- 0.02, n = 5, P < 0.05) but not
      in the dendrites (Delta0.16 +/- 0.005, n = 4). CONCLUSIONS: The mechanism of the
      hypoxia-induced increase in [Ca(2+)](i) differs between somata and dendrites. The
      N-methyl-D-aspartate channel of dendrites seems to be the main route of Ca(2+)
      influx.

PMID- 17554477
TI  - The Effect of intravitreal N-methyl-DL-aspartic acid on the electroretinogram in
      Royal College of surgeons rats.
AB  - PURPOSE: To investigate how the third-order neuronal response contributes to
      shaping the electroretinogram (ERG) in the Royal College of Surgeons (RCS) rat.
      METHODS: Full-field ERGs were recorded from dystrophic RCS rats (n = 30) at 4, 6,
      8, 10, 12, or 14 weeks of age in response to different stimulus intensities
      (maximum intensity, 0.84 log cd-s/m(2)). N-methyl-DL: -aspartic acid (NMDA, 5 mM)
      was injected into the vitreous cavity of the right eyes to eliminate the third
      order neuronal response. The left eyes received the vehicle and served as
      controls. The third-order neuronal response was isolated by digitally subtracting
      waveforms of the NMDA-injected eyes from those of the control eyes. RESULTS: The
      ERG a- and b-waves deteriorated with the age of the rat. The third-order neuronal
      response was preserved to a greater degree than the b-wave despite progression of
      photoreceptor degeneration. Intravitreal injection of NMDA attenuated the a-wave
      and enhanced the b-wave across the stimulus range from low to middle intensities.
      This tendency became more pronounced with advancing rat age. In aged dystrophic
      RCS rats this phenomenon was seen even at maximum intensity. The difference
      between NMDA-injected and vehicle-injected eyes was larger for the threshold than
      for the maximum amplitude at each examined time point (P < 0.001). Intravitreal
      injection of NMDA decreased implicit times of the a- and b-waves after the rats
      reached 8 weeks of age (P < 0.005 for the a-wave). CONCLUSION: With advancing
      photoreceptor degeneration, the third-order neuronal response made a greater
      contribution to shaping the a- and b-waves in dystrophic RCS rats.

PMID- 17554479
TI  - Visual acuity prognosis after anterior chamber air replacement to prevent pseudo
      anterior chamber formation after deep lamellar keratoplasty.
AB  - PURPOSE: To investigate the prognosis of patients who received anterior chamber
      air replacement after deep lamellar keratoplasty (DLKP) during the study period,
      January 1995 to April 2000. METHODS: The records were studied of 47 patients (54
      eyes) (60.6 +/- 21.3 years of age) who underwent DLKP at Dokkyo University
      Hospital. Visual acuity and endothelial cell loss were assessed in patients (1)
      with and without Descemet's membrane perforation; (2) with and without the use of
      anterior chamber air replacement, and for different durations of air replacement;
      and (3) in the presence or absence of a pseudo-anterior chamber, and in relation
      to its duration if present. RESULTS: No significant differences in relation to
      the above three items were found in endothelial cell loss in study years 1 to 5.
      Average best visual acuity was 0.61 in perforated eyes, 0.54 in unperforated
      eyes, 0.54 in eyes that received air replacement, and 0.57 in eyes that did not.
      The average best visual acuity was 0.38 in eyes with a pseudo-anterior chamber
      and 0.68 in eyes without one. There was a significant correlation between the
      duration of the pseudo-anterior chamber and loss of visual acuity. CONCLUSIONS:
      The prolongation of a pseudo-anterior chamber eventually impairs visual acuity,
      whereas anterior chamber air replacement, used to prevent the development of a
      pseudo-anterior chamber, causes minimal endothelial cell damage. Anterior chamber
      air replacement, therefore, is an effective technique by which to prevent the
      development of a pseudo-anterior chamber.

PMID- 17554480
TI  - Development of an instrument for measurement of light scattering at the corneal
      epithelial basement membrane in diabetic patients.
AB  - PURPOSE: Diabetic complications are associated with abnormality of the basement
      membranes. We have developed a light-scattering detection system (LSDS)
      specifically for measurement of light scattering at the corneal epithelial
      basement membrane, and have determined the reproducibility and clinical
      significance of the results obtained by the LSDS in diabetic patients. METHODS:
      Thirty nondiabetic controls and 40 diabetic subjects participated in the study.
      Light scattering at the corneal epithelial basement membrane was measured with
      the LSDS. RESULTS: The measurement of light scattering at the corneal basement
      membrane was found to be reproducible. The LSDS index (mean +/- SD) was 28.1 +/-
      4.8 in controls, 35.7 +/- 6.3 in mild diabetic retinopathy subjects, and 42.7 +/-
      8.6 in severe diabetic retinopathy subjects. This demonstrated that the LSDS
      index at the corneal basement membrane is proportional to the extent of diabetic
      retinopathy. CONCLUSIONS: Measurement of light scattering at the corneal
      epithelial basement membrane is possible with the LSDS, is relatively easy to
      perform, and is reproducible. The LSDS may prove suitable for the early detection
      of diabetic ocular complications.

PMID- 17554481
TI  - Infliximab treatment for ocular and extraocular manifestations of Behcet's
      disease.
AB  - PURPOSE: To assess the efficacy and safety of infliximab in the treatment of
      sight-threatening uveitis and extraocular manifestations in patients with
      Behcet's disease. METHODS: Twelve patients with Behcet's disease and uveitis were
      treated with infliximab after unsuccessful therapy with other immunosuppressive
      drugs. The main outcome measures were as follows: the number of uveitis relapses,
      the number of Behcet's disease-related extraocular lesions, and the amount of
      corticosteroids administered during the treatment as well as during an equal
      prior period of time while the patients were on other immunosuppressive agents.
      Visual acuity was recorded at the beginning of infliximab therapy and at the end
      of follow-up, and was defined as stable if it did not change from baseline,
      increased if it showed at least one line of improvement from baseline, and
      decreased if it showed at least a one line decrease from baseline. RESULTS:
      During an average follow-up of 16.67 +/- 7.63 months (median, 15 months), 11
      patients (91.6%) showed a reduction in the number of ocular relapses
      (relapse/month, from 0.35 +/- 0.17 to 0.12 +/- 0.17, P < 0.001). All of the
      patients (n = 11) who were taking corticosteroids before infliximab were able to
      reduce the amount of corticosteroids taken daily during infliximab treatment
      (from 24.33 +/- 10.84 mg/prednisone per day to 8.97 +/- 6.81 mg/prednisone per
      day, P < 0.001), and all presented with a reduced onset of extraocular
      manifestations of Behcet's disease (mean total number, from 2.83 +/- 3.61 to 1.51
      +/- 2.35, P = 0.039). One patient, who had to stop treatment 2 months after
      starting because of the onset of pulmonary tuberculosis, showed the same number
      of relapses during infliximab treatment but was able to reduce the mean daily
      corticosteroid dose. Visual acuity increased by one or more lines in three eyes
      (12.5%) and remained unchanged in 87.5% of the eyes. Infliximab-related side
      effects appeared in four patients (33.3%). CONCLUSIONS: Infliximab was effective
      in the treatment of uveitis in these Behcet's disease patients, significantly
      reducing the number of ocular relapses and making possible a significant
      reduction in the daily dose of corticosteroids administered. Extraocular
      manifestations of Behcet's disease were also controlled by infliximab.
      Nevertheless, side effects were not uncommon, and an extensive study of systemic
      conditions before infliximab administration had to be carried out to exclude
      systemic infection, particularly prior tuberculosis.

PMID- 17554482
TI  - Measurement of retinal nerve fiber layer thickness and macular volume for
      glaucoma detection using optical coherence tomography.
AB  - PURPOSE: To evaluate retinal nerve fiber layer (RNFL) thickness and macular
      volume in normal eyes and in the eyes of patients with glaucoma, and to compare
      the usefulness of these measurements in diagnosing glaucomatous eyes. METHODS:
      Eighty-one eyes were divided into three groups: normal control (n = 31), early
      glaucoma [n = 31, mean deviation (MD) >or= -6 dB], and advanced glaucoma (n = 19,
      MD < -6 dB). The RNFL thickness and macular volume were measured using Stratus
      OCT (optical coherence tomography). Then, the diagnostic power of these
      parameters was evaluated. RESULTS: In eyes with early glaucoma, RNFL thickness
      was decreased significantly in eight of the 12 peripapillary sectors, and macular
      volume was decreased significantly in six of the nine macular sectors, compared
      with normal eyes. In the advanced glaucoma eyes, RNFL and macular volume were
      decreased throughout, except in RNFL thickness in the papillomacular region, and
      in retinal thickness in the foveal region. The area under the receiver-operating
      characteristic curve (AUROC) of the average RNFL (0.963) was larger than the
      macular volume (0.919). CONCLUSIONS: Both peripapillary RNFL thickness and
      macular volume were decreased even in the early stage of glaucoma. Average RNFL
      thickness had greater diagnostic power than macular volume.

PMID- 17554483
TI  - Results of visual acuity and foveal thickness in diabetic macular edema after
      vitrectomy.
AB  - PURPOSE: To report results of an investigation of visual acuity (VA) and foveal
      thickness in diabetic macular edema (DME) patients after vitrectomy. METHODS: A
      retrospective study was performed of the records of 47 patients (61 eyes) who
      received pars plana vitrectomy (PPV) for DME. All eyes were followed up for over
      6 months (mean, 24.8 months; range, 6-60 months). VA and foveal thickness
      evaluated by optical coherence tomography were reviewed preoperatively and
      postoperatively. RESULTS: Twenty-four-month follow-up data were available for 46
      of the 61 eyes (75%). VA at the final examination had improved by 0.2 log units
      or more in 34 of the 61 eyes (56%), remained unchanged in 21 eyes (34%), and
      worsened in six eyes (10%). Mean foveal thickness decreased by more than 20% of
      the preoperative value in 50 of the 61 eyes (82%), remained unchanged in ten eyes
      (16%), and increased by more than 20% in one eye (2%) at the final examination.
      Postoperative best-corrected visual acuity (BCVA) at both 12 and 24 months was
      significantly better than preoperative BCVA (P < 0.0001). Foveal thickness at 3
      months or later significantly decreased from the preoperative value (P < 0.0001),
      but remained unchanged in comparison with postoperative 12 months and 24 months
      values (P = 0.19). Preoperative VA and presence of cystoid macular edema (CME)
      were independently associated with final visual acuity (P = 0.001). CONCLUSIONS:
      PPV for DME effectively improved VA and reduced foveal thickness for a longer
      postoperative period. Better preoperative VA was associated with better final
      postoperative VA. The eyes without CME tended to have better final postoperative
      VA.

PMID- 17554484
TI  - Photodynamic therapy for age-related macular degeneration in Japanese patients:
      results after one year.
AB  - PURPOSE: To evaluate the effects of photodynamic therapy (PDT) with verteporfin 1
      year after treatment in Japanese patients with age-related macular degeneration
      (AMD) and subfoveal choroidal neovascularization. METHODS: Between May 2004 and
      March 2005, PDT was performed on 102 eyes of 98 patients (60 men and 38 women)
      with AMD and subfoveal choroidal neovascularization. Patients were followed for
      at least 12 months after PDT. RESULTS: The mean visual acuities in logarithm of
      the minimum angle of resolution (logMAR) units were 0.978 at baseline, 0.919 at 3
      months, 0.895 at 6 months, 0.892 at 9 months, and 0.874 at 12 months. After PDT,
      the logMAR visual acuity improved by >0.3 logMAR units or more in 28 eyes (27%)
      and deteriorated by >0.3 logMAR units or more in 13 eyes (13%). Stable or
      improved vision was achieved in 93% of patients with polypoidal choroidal
      vasculopathy (PCV). CONCLUSIONS: The visual outcome in our patients was similar
      to that of an earlier major Japanese study, and similar to or better than
      outcomes in Western studies. Differences between Caucasians and Japanese might
      influence the characteristics of PCV. It is possible that PDT is more effective
      for AMD patients with PCV than for other AMD patients. Further observations and
      longer follow-up are necessary.

PMID- 17554485
TI  - Neovascularization associated with large retinal pigment epithelial detachment in
      elderly Korean patients: subdivision according to indocyanine green angiographic
      features.
AB  - PURPOSE: In Korean patients, to subdivide the neovascular forms of age-related
      macular degeneration (AMD) associated with large retinal pigment epithelial
      detachment (PED), according to the indocyanine green angiographic features.
      METHODS: Indocyanine green angiograms (ICGA) of 67 elderly patients (72 eyes) who
      presented with a PED of at least 1 disc diameter were evaluated retrospectively.
      RESULTS: Polypoidal choroidal vasculopathy (PCV) and typical choroidal
      neovascularization (CNV)-associated PEDs were identified in 18 eyes (25%) and 19
      eyes (26%), respectively. In ten eyes (13.9%), the exact type of
      neovascularization, whether PCV or CNV, could not be determined. Pure serous PEDs
      were identified in seven eyes (10%). The remaining 18 eyes (25%) were classified
      as having retinal angiomatous proliferation (RAP)-associated PED based upon the
      angiographic findings of vascular connections between the retinal vasculature and
      the neovascular complex. CONCLUSIONS: Three subset groups of PCV, CNV, and RAP
      were present with similar frequency in neovascularized AMD with a large PED in
      these Korean patients. In particular, RAP, previously thought to be rare in Asian
      patients, was found to be present with considerable frequency.

PMID- 17554486
TI  - Mydriasis with light-near dissociation in Fisher's Syndrome.
AB  - BACKGROUND: Approximately 50% of patients with Fisher's syndrome show involvement
      of the pupillomotor fibers and present with mydriasis and light-near
      dissociation. However, it is uncertain whether this phenomenon is induced by an
      aberrant reinnervation mechanism as in tonic pupil, or is based on other
      mechanisms such as those associated with tectal pupils. CASES: We evaluated the
      clinical course and the pupillary responses in four of 27 patients with Fisher's
      syndrome who presented with bilateral mydriasis. OBSERVATIONS: The pupils of both
      eyes of the four patients were involved at the early stage of Fisher's syndrome.
      The pupils in patients 1 and 2 showed mydriasis with apparent light-near
      dissociation lasting for a significant period and had denervation
      supersensitivity to cholinergic agents. On the other hand, the pupils of patients
      3 and 4 were dilated and fixed to both light and near stimuli. CONCLUSIONS: Our
      observations indicate that the denervated iris sphincter muscles, which are
      supersensitive to the cholinergic transmitter, may play an important role in the
      expression of light-near dissociation in Fisher's syndrome.

PMID- 17554487
TI  - Interlamellar flap edema due to steroid-induced ocular hypertension after laser
      in situ keratomileusis.
AB  - BACKGROUND: Several recent studies have reported post-laser in situ
      keratomileusis (LASIK) complications related to a steroid-induced increase in
      intraocular pressure, including interface fluid and elevated intraocular pressure
      induced interlamellar stromal keratitis. CASES: We examined two cases of
      interlamellar flap edema due to steroid-induced ocular hypertension after
      uneventful laser in situ keratomileusis. OBSERVATIONS: Oral acetazolamide and
      discontinuance of topical steroids were effective for treating interlamellar
      stromal edema in both cases. CONCLUSION: A rise in intraocular pressure should be
      considered a cause of interlamellar stromal edema after LASIK.

PMID- 17554488
TI  - Eyelid schwannoma in a Korean woman.

PMID- 17554489
TI  - Unusually large plastic toy as a persisting conjunctival foreign body.

PMID- 17554490
TI  - Bilateral iris metastasis from endometrial carcinoma.

PMID- 17554491
TI  - Glycated albumin induces activation of activator protein-1 in retinal glial
      cells.

PMID- 17554492
TI  - Case of POEMS syndrome associated with bilateral macular detachment resolved by
      autologous peripheral blood stem cell transplantation.

PMID- 17554493
TI  - Long-term infliximab treatment for Behcet's disease.

PMID- 17554494
TI  - Mesectodermal leiomyoma confined to the posterior choroid.

PMID- 17554495
TI  - Pentavalent technetium-99m dimercaptosuccinic acid [99m Tc-(V)DMSA] brain
      scintitomography--a plausible non-invasive depicter of glioblastoma proliferation
      and therapy response.
AB  - The biological behavior and prognosis of gliomas depend largely on cellular
      proliferation, resistance to chemotherapy, and metastatic potential.
      Proliferative propensity has significant implications on patient management but
      its assessment requires tissue sampling; the non-invasive estimation of brain
      tumor proliferation represents therefore a major goal. Pentavalent technetium-99
      m dimercapto-succinic acid [99m Tc-(V)DMSA] is a tumor-seeking radiotracer
      displaying affinity for gliomas; its intracellular accumulation is directly
      linked to cell proliferation. We performed a tomographic 99m Tc-(V)DMSA brain
      scan in a 35-year-old male baring a recurrent glioblastoma multiforme, to depict
      its proliferative disposition. The patient had been diagnosed 14 months earlier
      and had been submitted to surgery, followed by adjuvant radiotherapy and
      temozolomide-based chemotherapy. On clinical suspicion of recurrence 5 months
      later, magnetic resonance imaging (MRI) revealed a lesion at the site of preceded
      surgery, which was treated by imatinib mesylate. No improvement was ascertained
      the following months and radiographic assessment verified tumor progression.
      Scintitomography revealed avid radiotracer uptake in the entirety of the lesion
      (the distribution of radioactivity closely conforming to the morphological tumor
      boundaries), an indication that the neoplasm demonstrated no substantial
      proliferation decline in response to imatinib. The patient deceased a few weeks
      later. Mounting in vivo and in vitro evidence indicates that 99m Tc-(V)DMSA is a
      credible non-invasive proliferation depicter, its cellular accumulation linked
      closely to phosphate uptake and kinase pathway activation. A potential role in
      patient management, prognosis estimation, and therapy response monitoring could
      occur for this tracer.

PMID- 17554496
TI  - Refinement of protein structure against non-redundant carbonyl 13C NMR
      relaxation.
AB  - Carbonyl (13)C' relaxation is dominated by the contribution from the (13)C'
      chemical shift anisotropy (CSA). The relaxation rates provide useful and non
      redundant structural information in addition to dynamic parameters. It is
      straightforward to acquire, and offers complimentary structural information to
      the (15)N relaxation data. Furthermore, the non-axial nature of the (13)C' CSA
      tensor results in a T(1)/T(2) value that depends on an additional angular
      variable even when the diffusion tensor of the protein molecule is axially
      symmetric. This dependence on an extra degree of freedom provides new geometrical
      information that is not available from the NH dipolar relaxation. A protocol that
      incorporates such structural restraints into NMR structure calculation was
      developed within the program Xplor-NIH. Its application was illustrated with the
      yeast Fis1 NMR structure. Refinement against the (13)C' T(1)/T(2) improved the
      overall quality of the structure, as evaluated by cross-validation against the
      residual dipolar coupling as well as the (15)N relaxation data. In addition,
      possible variations of the CSA tensor were addressed.

PMID- 17554497
TI  - 13C- 13C NOESY spectra of a 480 kDa protein: solution NMR of ferritin.
AB  - Molecular size has limited solution NMR analyses of proteins. We report (13)C
      (13)C NOESY experiments on a 480 kDa protein, the multi-subunit ferritin nanocage
      with gated pores. By exploiting (13)C-resonance-specific chemical shifts and spin
      diffusion effects, we identified 75% of the amino acids, with intraresidue C-C
      connectivities between nuclei separated by 1-4 bonds. These results show the
      potential of (13)C-(13)C NOESY for solution studies of molecular assemblies >100
      kDa.

PMID- 17554499
TI  - Decolorization and biodegradation of Indigo carmine by a textile soil isolate
      Paenibacillus larvae.
AB  - The potential of recently isolated bacteria Paenibacillus larvae for the
      effective decolorization of Indigo carmine was evaluated. The effects of
      operational parameters (temperature, pH, dye concentration, shaking/non shaking)
      were tested. Maximum extent of decolorization was observed when the medium was
      incorporated with 10 g/l of yeast extract and peptone. Decolorization was
      strongly inhibited at non-shaken conditions as well as incorporation of inorganic
      sources (sodium nitrite and ammonium chloride) in the medium. Maximum
      decolorization was observed at 30 degrees C (100%) and 40 degrees C (92%) at 8 h
      of incubation. The LC-MS and NMR analysis confirms the oxidation of Indigo
      carmine . The primary degradation products were found to be Isatin sulfonic acid
      and anthranilicacid.

PMID- 17554498
TI  - Fractional 13C enrichment of isolated carbons using [1-13C]- or [2- 13C]-glucose
      facilitates the accurate measurement of dynamics at backbone Calpha and side
      chain methyl positions in proteins.
AB  - A simple labeling approach is presented based on protein expression in [1-(13)C]-
      or [2-(13)C]-glucose containing media that produces molecules enriched at methyl
      carbon positions or backbone C(alpha) sites, respectively. All of the methyl
      groups, with the exception of Thr and Ile(delta1) are produced with isolated
      (13)C spins (i.e., no (13)C-(13)C one bond couplings), facilitating studies of
      dynamics through the use of spin-spin relaxation experiments without artifacts
      introduced by evolution due to large homonuclear scalar couplings. Carbon-alpha
      sites are labeled without concomitant labeling at C(beta) positions for 17 of the
      common 20 amino acids and there are no cases for which (13)C(alpha)-(13)CO spin
      pairs are observed. A large number of probes are thus available for the study of
      protein dynamics with the results obtained complimenting those from more
      traditional backbone (15)N studies. The utility of the labeling is established by
      recording (13)C R (1rho) and CPMG-based experiments on a number of different
      protein systems.

PMID- 17554500
TI  - Presynaptic inhibition of glutamate release by neuropeptides: use-dependent
      synaptic modification.
AB  - Neuropeptides are signaling molecules that interact with G-protein coupled
      receptors located both pre- and postsynaptically. Presynaptically, these
      receptors are localized in axons and terminals away from presynaptic
      specializations. Neuropeptides are stored in dense core vesicles that are
      distinct from the clear synaptic vesicles containing classic neurotransmitters
      such as glutamate and GABA. Because they require a stronger Ca(2+) signal than
      synaptic vesicles, dense core vesicles do not release neuropeptides with single
      action potentials but rather require high-frequency trains. Thus, neuropeptides
      only modulate strongly stimulated synapses, providing negative or positive
      feedback. Many neuropeptides have been found to inhibit glutamate release from
      presynaptic terminals, and the major mechanism is likely direct interaction of
      betagamma G-protein subunits with presynaptic proteins such as SNARE (soluble N
      ethylmaleimide-sensitive factor attachment protein receptor). The use of mouse
      genetic models and specific receptor antagonists are beginning to unravel the
      function of inhibitory neuropeptides. The opioid receptors kappa and mu, which
      are activated by endogenous opioid peptides such as dynorphin, enkephalin, and
      possibly the endomorphins, are important in modulating pain transmission.
      Dynorphin, nociceptin/orphanin FQ, and somatostatin and its related peptide
      cortistatin appear to play a role in modulation of learning and memory.
      Neuropeptide Y has important functions in ingestive behavior and also in
      entraining circadian rhythms. The existence of neuropeptides greatly expands the
      computational ability of the brain by providing additional levels of modulation.

PMID- 17554501
TI  - GABA(C) receptors in retina and brain.
AB  - The expression of GABA(C) receptors has long been regarded as a specific property
      of bipolar cells in the inner retina where they control the information transfer
      from bipolar to retinal ganglion cells. A number of recent anatomical and
      physiological studies, however, have provided evidence that GABA(C) receptors are
      also expressed in many brain structures apart from the retina. The presence of
      GABA(C) receptors in many GABAergic neurons suggests that this receptor type may
      be involved in the regulation of local inhibition. This chapter focuses on the
      distribution of GABA(C) receptors and their possible function in various brain
      areas.

PMID- 17554502
TI  - Mobilization of bone marrow-derived progenitors.
AB  - Bone marrow (BM) is a source of various stem and progenitor cells in the adult,
      and it is able to regenerate a variety of tissues following transplantation. In
      the 1970s the first BM stem cells identified were hematopoietic stem cells
      (HSCs). HSCs have the potential to differentiate into all myeloid (including
      erythroid) and lymphoid cell lineages in vitro and reconstitute the entire
      hematopoietic and immune systems following transplantation in vivo. More
      recently, nonhematopoietic stem and progenitor cells have been identified that
      can differentiate into other cell types such as endothelial progenitor cells
      (EPCs), contributing to the neovascularization of tumors as well as ischemic
      tissues, and mesenchymal stem cells (MSCs), which are able to differentiate into
      many cells of ectodermal, endodermal, and mesodermal origins in vitro as well as
      in vivo. Following adequate stimulation, stem and progenitor cells can be forced
      out of the BM to circulate into the peripheral blood, a phenomenon called
      "mobilization." This chapter reviews the molecular mechanisms behind mobilization
      and how these have led to the various strategies employed to mobilize BM-derived
      stem and progenitor cells in experimental and clinical settings. Mobilization of
      HSCs will be reviewed first, as it has been best-explored--being used extensively
      in clinics to transplant large numbers of HSCs to rescue cancer patients
      requiring hematopoietic reconstitution--and provides a paradigm that can be
      generalized to the mobilization of other types of BM-derived stem and progenitor
      cells in order to repair other tissues.

PMID- 17554503
TI  - Role of endothelial nitric oxide in bone marrow-derived progenitor cell
      mobilization.
AB  - Mobilization and recruitment of bone marrow-derived progenitor cells (BMDPCs)
      play an important role in postischemic tissue repair. Patients with coronary
      artery disease (CAD) or peripheral vascular disease (PVD) exhibit endothelial
      dysfunction, and as a result are likely to have a reduced number of progenitor
      cells mobilized in their peripheral circulation following ischemic injury.
      Identification of eNOS independent pathways for BMDPC mobilization may have
      important therapeutic value in this patient population. To identify such
      mechanisms we investigated the effect of granulocyte-colony stimulating factor
      (GCSF) and stem cell factor (SCF) in eNOS-KO mice with and without surgical hind
      limb ischemia. Our results suggest that BMDPC mobilization can be achieved via
      activation of NO-independent pathways.

PMID- 17554504
TI  - Immune plasticity of bone marrow-derived mesenchymal stromal cells.
AB  - Isolated from simple bone marrow aspirates, mesenchymal stromal cells (MSCs) can
      be easily expanded ex vivo and differentiated into various cell lineages. Because
      they are present in humans of all ages, are harvested in the absence of prior
      mobilization and preserve their plasticity following gene modification, MSCs are
      particularly attractive for cell-based medicine. One of the most fascinating
      properties of ex vivo expanded MSCs is their ability to suppress ongoing immune
      responses, both in vitro and in vivo. Although not fully understood, the
      immunosuppressive properties of MSCs have been reported to affect the function of
      a broad range of immune cells, including T cells, antigen-presenting cells,
      natural killer cells and B cells. Whereas successful harnessing of these
      immunosuppressive properties might one day open the door to the development of
      new cell-based strategies for the control of graft-versus-host and other
      autoimmune diseases, recent studies suggest that the immune-modulating properties
      of MSCs are far more complex than first thought. Reminiscent of the dichotomy of
      function of dendritic cells (DCs), which can act as potent activators or potent
      suppressors of immune responses, new studies including our own work has shown
      that MSCs in fact possess the dual ability to suppress or activate immune
      responses. In this review, we summarize the different biological properties of
      MSCs and discuss the current literature on the complex mechanism of immune
      modulation mediated by ex vivo expanded MSCs.

PMID- 17554505
TI  - Bone marrow-derived cells: the influence of aging and cellular senescence.
AB  - During the course of an entire lifespan, tissue repair and regeneration is made
      possible by the presence of adult stem cells. Stem cell expansion, maintenance,
      and differentiation must be tightly controlled to assure longevity. Hematopoietic
      stem cells (HSC) are greatly solicited given the daily high blood cell turnover.
      Moreover, several bone marrow-derived cells including HSC, mesenchymal stromal
      cells (MSC), and endothelial progenitor cells (EPC) also significantly contribute
      to peripheral tissue repair and regeneration, including tumor formation.
      Therefore, factors influencing bone marrow-derived cell proliferation and
      functions are likely to have a broad impact. Aging has been identified as one of
      these factors. One hypothesis is that aging directly affects stem cells as a
      consequence of exhaustive proliferation. Alternatively, it is also possible that
      aging indirectly affects stem cells by acting on their microenvironment. Cellular
      senescence is believed to have evolved as a tumor suppressor mechanism capable of
      arresting growth to reduce risk of malignancy. In opposition to apoptosis,
      senescent cells accumulate in tissues. Recent evidence suggests their
      accumulation contributes to the phenotype of aging. Senescence can be activated
      by both telomere-dependent and telomere-independent pathways. Genetic alteration,
      genome-wide DNA damage, and oxidative stress are inducers of senescence and have
      recently been identified as occurring in bone marrow-derived cells. Below is a
      review of the link between cellular senescence, aging, and bone marrow-derived
      cells, and the possible consequences aging may have on bone marrow trans
      plantation procedures and emerging marrow-derived cell-based therapies.

PMID- 17554506
TI  - Involvement of marrow-derived endothelial cells in vascularization.
AB  - Until recently, the adult neovasculature was thought to arise only through
      angiogenesis, the mechanism by which new blood vessels form from preexisting
      vessels through endothelial cell migration and proliferation. However, recent
      studies have provided evidence that postnatal neovasculature can also arise
      though vasculogenesis, a process by which endothelial progenitor cells are
      recruited and differentiate into mature endothelial cells to form new blood
      vessels. Evidence for the existence of endothelial progenitors has come from
      studies demonstrating the ability of bone marrow-derived cells to incorporate
      into adult vasculature. However, the exact nature of endothelial progenitor cells
      remains controversial. Because of the lack of definitive markers of endothelial
      progenitors, the in vivo contribution of progenitor cells to physiological and
      pathological neovascularization remains unclear. Early studies reported that
      endothelial progenitor cells actively integrate into the adult vasculature and
      are critical in the development of many types of vascular-dependent disorders
      such as neoplastic progression. Moreover, it has been suggested that endothelial
      progenitor cells can be used as a therapeutic strategy aimed at promoting
      vascular growth in a variety of ischemic diseases. However, increasing numbers of
      studies have reported no clear contribution of endothelial progenitors in
      physiological or pathological angiogenesis. In this chapter, we discuss the
      origin of the endothelial progenitor cell in the embryo and adult, and we discuss
      the cell's link to the primitive hematopoietic stem cell. We also review the
      potential significance of endothelial progenitor cells in the formation of a
      postnatal vascular network and discuss the factors that may account for the
      current lack of consensus of the scientific community on this important issue.

PMID- 17554507
TI  - Comparison of intracardiac cell transplantation: autologous skeletal myoblasts
      versus bone marrow cells.
AB  - An increasing number of patients living with cardiovascular disease (CVD) and
      still unacceptably high mortality created an urgent need to effectively treat and
      prevent disease-related events. Within the past 5 years, skeletal myoblasts
      (SKMBs) and bone marrow (or blood)-derived mononuclear cells (BMNCs) have
      demonstrated preclinical efficacy in reducing ischemia and salvaging already
      injured myocardium, and in preventing left ventricular (LV) remodeling,
      respectively. These findings have been translated into clinical trials, so far
      totaling over 200 patients for SKMBs and over 800 patients for BMNCs. These
      safety/feasibility and early phase II studies showed promising but somewhat
      conflicting symptomatic and functional improvements, and some safety concerns
      have arisen. However, the patient population, cell type, dose, time and mode of
      delivery, and outcome measures differed, making comparisons problematic. In
      addition, the mechanisms through which cells engraft and deliver their beneficial
      effects remain to be fully elucidated. It is now time to critically evaluate
      progress made and challenges encountered in order to select not only the most
      suitable cells for cardiac repair but also to define appropriate patient
      populations and outcome measures. Reiterations between bench and bedside will
      increase the likelihood of cell therapy success, reduce the time to development
      of combined of drug- and cell-based disease management algorithms, and offer
      these therapies to patients to achieve a greater reduction of symptoms and allow
      for a sustained improvement of quality of life.

PMID- 17554508
TI  - Ischemic tissue repair by autologous bone marrow-derived stem cells: scientific
      basis and preclinical data.
AB  - The success of therapies targeting acute myocardial ischemia and the aging of the
      population due to improved general medical care has resulted in an increasing
      population of patients with chronic myocardial ischemia and congestive heart
      failure who remain symptomatic despite having exhausted the currently available
      therapeutic options. In this chapter we review the scientific underpinnings of
      autologous bone marrow-derived cell therapy and the early clinical experience
      that has fuelled interest in this approach.

PMID- 17554509
TI  - Cell therapy and gene therapy using endothelial progenitor cells for vascular
      regeneration.
AB  - The isolation of endothelial progenitor cells (EPCs) derived from adult bone
      marrow (BM) was an epoch-making event for the recognition of "neovessel
      formation" occurring as physiological and pathological responses in adults. The
      finding that EPCs home to sites of neovascularization and differentiate into
      endothelial cells (ECs) in situ is consistent with "vasculogenesis," a critical
      paradigm well described for embryonic neovascularization, but proposed recently
      in adults, in which a reservoir of stem or progenitor cells contributes to
      vascular organogenesis. EPCs have also been considered as therapeutic agents to
      supply the potent origin of neovascularization under pathological conditions.
      Considering the regenerative implications, gene modification of stem cells has
      advantages over conventional gene therapy. Ex vivo gene transfection of stem
      cells may avoid administration of vectors and vehicles into the recipient
      organism. Stem cells isolated from adults may exhibit age-related, genetic, or
      acquired disease-related impairment of their regenerative ability.
      Transcriptional or enzymatic gene modification may constitute an effective means
      to maintain, enhance, or inhibit EPCs' capacity to proliferate or differentiate.
      This chapter provides an update of EPC biology as well as EPCs' potential use for
      therapeutic regeneration.

PMID- 17554510
TI  - Mesenchymal stem cells for cardiac regenerative therapy.
AB  - Until recently, the concept of treating the injured or failing heart by
      generating new functional myocardium was considered physiologically impossible.
      Major scientific strides in the past few years have challenged the concept that
      the heart is a post-mitotic organ, leading to the hypothesis that cardiac
      regeneration could be therapeutically achieved. Bone marrow-derived adult stem
      cells were among the first cell populations that were used to test this
      hypothesis. Animal studies and early clinical experience support the concept that
      therapeutically delivered mesenchymal stem cells (MSCs) safely improve heart
      function after an acute myocardial infarction (MI). MSCs produce a variety of
      cardio-protective signalling molecules, and have the ability to differentiate
      into both myocyte and vascular lineages. Additionally, MSCs are attractive as a
      cellular vehicle for gene delivery, cell transplantation or for tissue
      engineering because they offer several practical advantages. They can be obtained
      in relatively large numbers through standard clinical procedures, and they are
      easily expanded in culture. The multi-lineage potential of MSC, in combination
      with their immunoprivileged status, make MSCs a promising source for cell therapy
      in cardiac diseases. Here we provide an overview of biological characteristics of
      MSCs, experimental animal studies and early clinical trials with MSCs. In
      addition, we discuss the routes of cell delivery, cell tracking experiments and
      current knowledge of the mechanistic underpinnings of their action.

PMID- 17554511
TI  - Autotransplantation of bone marrow-derived stem cells as a therapy for
      neurodegenerative diseases.
AB  - Neurodegenerative diseases are characterized by a progressive degeneration of
      selective neural populations. This selective hallmark pathology and the lack of
      effective treatment modalities make these diseases appropriate candidates for
      cell therapy. Bone marrow-derived mesenchymal stem cells (MSCs) are self-renewing
      precursors that reside in the bone marrow and may further be exploited for
      autologous transplantation. Autologous transplantation of MSCs entirely
      circumvents the problem of immune rejection, does not cause the formation of
      teratomas, and raises very few ethical or political concerns. More than a few
      studies showed that transplantation of MSCs resulted in clinical improvement.
      However, the exact mechanisms responsible for the beneficial outcome have yet to
      be defined. Possible rationalizations include cell replacement, trophic factors
      delivery, and immunomodulation. Cell replacement theory is based on the idea that
      replacement of degenerated neural cells with alternative functioning cells
      induces long-lasting clinical improvement. It is reasoned that the transplanted
      cells survive, integrate into the endogenous neural network, and lead to
      functional improvement. Trophic factor delivery presents a more practical short
      term approach. According to this approach, MSC effectiveness may be credited to
      the production of neurotrophic factors that support neuronal cell survival,
      induce endogenous cell proliferation, and promote nerve fiber regeneration at
      sites of injury. The third potential mechanism of action is supported by the
      recent reports claiming that neuroinflammatory mechanisms play an important role
      in the pathogenesis of neurodegenerative disorders. Thus, inhibiting chronic
      inflammatory stress might explain the beneficial effects induced by MSC
      transplantation. Here, we assemble evidence that supports each theory and review
      the latest studies that have placed MSC transplantation into the spotlight of
      biomedical research.

PMID- 17554512
TI  - Stem cells as a treatment for chronic liver disease and diabetes.
AB  - Advances in stem cell biology and the discovery of pluripotent stem cells have
      made the prospect of cell therapy and tissue regeneration a clinical reality.
      Cell therapies hold great promise to repair, restore, replace or regenerate
      affected organs and may perform better than any pharmacological or mechanical
      device. There is an accumulating body of evidence supporting the contribution of
      adult stem cells, in particular those of bone marrow origin, to liver and
      pancreatic islet cell regeneration. In this review, we will focus on the cell
      therapy for the diseased liver and pancreas by adult haematopoietic stem cells,
      as well as their possible contribution and application to tissue regeneration.
      Furthermore, recent progress in the generation, culture and targeted
      differentiation of human haematopoietic stem cells to hepatic and pancreatic
      lineages will be discussed. We will also explore the possibility that stem cell
      technology may lead to the development of clinical modalities for human liver
      disease and diabetes.

PMID- 17554513
TI  - The participation of mesenchymal stem cells in tumor stroma formation and their
      application as targeted-gene delivery vehicles.
AB  - Recent evidence suggests that mesenchymal stem cells (MSC) selectively
      proliferate to tumors and contribute to the formation of tumor-associated stroma.
      The biological rationale for tumor recruitment of MSC remains unclear but may
      represent an effort of the host to blunt tumor cell growth and improve survival.
      There is mounting experimental evidence that normal stromal cells can revert
      malignant cell behavior, and separate studies have demonstrated that stromal
      cells can enhance tumor progression after acquisition of tumor-like genetic
      lesions. Together, these observations support the rationale for modifying normal
      MSC to deliver therapeutic proteins directly into the tumor microenvironment.
      Modified MSC can produce high concentrations of antitumor proteins directly
      within the Tumor mass, which have been shown to blunt tumor growth kinetics in
      experimental animal model systems. In this chapter we will address the biological
      properties of MSC within the tumor microenvironment and discuss the potential use
      of MSC and other bone marrow-derived cell populations as delivery vehicles for
      antitumor proteins.

PMID- 17554514
TI  - [Hyperthermia and hypothermia. Effects on the cardiovascular system].
AB  - Heat and cold are environmental factors which severely affect the cardiovascular
      system. An increase in the body core temperature (hyperthermia) from
      approximately 36.5 to 39 degrees C causes a doubling of the cardiac output. In
      connection with vasoconstriction in the splanchnic circulation and in skeletal
      muscle this results in large increases of skin blood flow. The underlying
      vasodilatation is evoked by reflex regulation of the efferent sympathetic system.
      While there is a reduction of alpha-adrenergic vasoconstriction, there is also
      evidence for active sympathetic cholinergic and nitric oxide-dependent
      vasodilatation. In the presence of risk factors, e.g. age and diabetes, the
      circulatory adaptation to heat stress may be compromised. During a reduction of
      the core temperature (hypothermia) there is a reflex adrenergic vasoconstriction
      (noradrenalin) of the skin. Cardiac output falls below a core temperature of 34
      degrees C due to increasing bradycardia. The reflex vasoconstriction following
      cold exposure may be aggravated at higher ages, which may cause steeper increases
      of arterial blood pressure. Due to the reflex nature, the regulatory processes
      are severely compromised during anaesthesia.

PMID- 17554515
TI  - [Paper-assisted digital Mission documentation in air rescue services. Quality
      management in preclinical emergency medicine].
AB  - BACKGROUND: Recording of adequate mission data is of utmost importance in
      prehospital emergency medicine. For this, a nationwide uniform core dataset for
      prehospital data reporting, the so-called MIND 2, was introduced. With this
      procedure adequate information about structure and outcome quality, but only
      little information about process quality, can be obtained. Regarding the quality
      of data recording, primarily computer-based techniques are superior to other
      techniques. Against this background, the aim of this study was to develop a
      documentation system, which sets new standards regarding documentation dataset
      and documentation quality. RESULTS: A primarily computer-based documentation
      system based on the "digital paper" technology was achieved. This technology
      allows conventional data entry via a (digital) pen and documentation on
      conventional paper. As the core-dataset MIND 2 was realized - furthermore, the
      measurements performed during prehospital management as well as data on vital
      signs (blood pressure, heart frequency, S(a)O(2), p(et)CO(2) etc.) were included
      into routine data recording. Integration of this documentation system into an
      already existing medical quality management system was achieved via a defined
      interface. Testing of this new system over a 3-month period at the helicopter
      emergency medical service (HEMS) "Christoph 22" showed a high degree of
      functionality and stability of the system. Serious problems, especially a total
      break-down of the whole system, were not observed during the study period.
      CONCLUSIONS: The new data recording concept, which is based on the "digital
      paper" technology, has proven to be completely satisfactory with respect to
      functionality and documentation quality during the test period.

PMID- 17554516
TI  - [Therapy of hyperthermia in sepsis and septic shock. Necessary or injurious?].
AB  - In critically ill patients fever is associated with an increased morbidity and
      mortality rate. However, it remains unclear whether fever is an associated
      symptom of the underlying severe disease or a stimulator of specific
      pathophysiological cascades considered responsible for a deleterious outcome.
      Hyperthermia per se induces systemic changes like increased energy and oxygen
      demands, tachycardia, or fluid loss which might be harmful especially in septic
      patients due to congestion of the cardiovascular system. In this constellation a
      reduction of fever by antipyretic strategies might be indicated to decrease
      oxygen and energy demands. On the other hand the increasing body temperature
      obviously plays an important role in the inflammatory hemostasis during
      infections. Fever optimises humoral and cellular responses to infection and has
      some direct effects on bacteria and other microorganisms. Therefore, in severe
      sepsis or septic shock, fever reduction might impair the immune competency of the
      patients. According to the currently available evidence a body temperature higher
      than 40 degrees C is definitely harmful and should be treated in any case. A
      temperature range between 36 degrees C and 39 degrees C should be achieved for
      patients with severe sepsis and septic shock. At present there are no data
      showing the superiority of any of the different antipyrectic strategies in septic
      patients. Hence, external cooling with cold blankets or other devices may induce
      shivering of the muscles with a substantial increase of oxygen demand and is
      hardly tolerated in conscious patients. However, antipyretic therapy in patients
      with severe sepsis or septic shock should be indicated while considering the
      individual pathophysiology of every patient.

PMID- 17554517
TI  - [Results of mechanical ileus].

PMID- 17554519
TI  - Heterosis for horticultural traits in broccoli.
AB  - Over the last three decades, broccoli (Brassica oleracea L., Italica Group)
      hybrids made by crossing two inbred lines replaced open-pollinated populations to
      become the predominant type of cultivar. The change to hybrids evolved with
      little or no understanding of heterosis or hybrid vigor in this crop. Therefore,
      the purpose of the present study was to determine levels of heterosis expressed
      by a set of hybrids derived by crossing relatively elite, modern inbreds (n = 9).
      An additional objective was to determine if PCR-based marker derived genetic
      similarities among the parents can be useful to predict heterosis in this crop.
      Thirty-six hybrids derived from a diallel mating design involving nine parents
      were evaluated for five horticultural characters including the head
      characteristics of head weight, head stem diameter, and maturity (e.g., days from
      transplant to harvest), and the plant vigor characteristics of plant height, and
      plant width in four environments. A total of 409 polymorphic markers were
      generated by 24 AFLP, 23 SRAP and 17 SSR primer combinations. Euclidean distances
      between parents were determined based on phenotypic traits. About half of the
      hybrids exhibited highparent heterosis for head weight (1-30 g) and stem diameter
      (0.2-3.5 cm) when averaged across environments. Almost all hybrids showed
      highparent heterosis for plant height (1-10 cm) and width (2-13 cm). Unlike other
      traits, there was negative heterosis for maturity, indicating that heterosis for
      this character in hybrids is expressed as earliness. Genetic similarity estimates
      among the nine parental lines ranged from 0.43 to 0.71 and were significantly and
      negatively correlated with highparent heterosis for all traits except for stem
      diameter and days from transplant to harvest. Euclidean distances were not
      correlated with heterosis. With modern broccoli inbreds, less heterosis was
      observed for head characteristics than for traits that measured plant vigor. In
      addition, genetic similarity based on molecular markers was more highly
      correlated with plant vigor characteristics than head traits. Unlike with
      molecular marker-based estimates of genetic similarity, euclidean distance
      determined using phenotypic trait data was not predictive of heterosis. In
      conclusion, this study has documented heterosis in Brassica oleracea L., and the
      ability to predict heterosis in this crop using molecular marker-based estimates
      of genetic similarity among parents used in producing the hybrid.

PMID- 17554518
TI  - Recombinant full-length human IgG1s targeting hormone-refractory prostate cancer.
AB  - We have used a naive human single-chain fragment variable (scFv) library as a
      source of random shape repertoire to directly probe the altered surface chemistry
      of tumor cells. We reported previously the identification of more than 90
      internalizing phage monoclonal antibodies targeting prostate cancer cells,
      including those that are hormone refractory. In this report, we describe the
      conversion of a panel of those scFvs into full-length human immunoglobulins
      (IgGs) and show that tumor specificity is retained. We have further shown that
      antibodies isolated from a naive phage display library can nevertheless be of
      high affinity towards target tumor cells. In addition, full-length IgGs retain
      the functionality of parental scFvs including the ability to rapidly enter target
      cells through receptor-mediated endocytosis and thereby to mediate efficient and
      specific intracellular payload delivery to tumor cells. We have used recombinant
      IgGs to immunoprecipitate target antigens and analyzed their molecular
      composition by mass spectrometry. We have identified one target antigen as
      activated leukocyte cell adhesion molecule (ALCAM)/MEMD/CD166 and have further
      studied tissue specificity of this internalizing ALCAM epitope by
      immunohistochemistry. Our study shows that cell type-specific internalizing human
      antibody can be readily identified from a naive phage antibody display library,
      characterized with regards to sequence, affinity, tissue specificity, and antigen
      identity, and modified genetically and chemically to generate various forms of
      targeted therapeutics.

PMID- 17554520
TI  - Enoxaparin therapy for arterial thrombosis in infants with congenital heart
      disease.
AB  - OBJECTIVE: To investigate efficacy and safety of enoxaparin for catheter-related
      arterial thrombosis in infants with congenital heart disease. DESIGN: Prospective
      observational study. SETTING: Pediatric Intensive Care and Cardiology Unit at the
      University Children's Hospital of Zurich. PATIENTS: A cohort of 32[Symbol: see
      text]infants aged 0-12[Symbol: see text]months treated with enoxaparin for
      catheter-related arterial thrombosis from 2002 to 2005. MEASUREMENTS: Dose
      requirements of enoxaparin, resolution of thrombosis by Doppler ultrasound, and
      bleeding complications. RESULTS: Catheter-related arterial thrombosis was located
      in the iliac/femoral arteries in 31 (97%) infants and aorta in 1 infant, and was
      related to indwelling catheters and cardiac catheterization in 17 (53%) and 15
      (47%) cases, respectively. Newborns required increased doses of enoxaparin to
      achieve therapeutic anti-FXa levels (mean 1.62[Symbol: see text]mg/kg per dose)
      compared with infants aged 2-12 months (mean 1.12 mg/kg per dose; p=0.0002).
      Complete resolution of arterial thrombosis occurred in 29 (91%) infants at a mean
      of 23 days after initiation of enoxaparin therapy. Partial or no resolution was
      observed in 1 (3%) and 2 (6%) infants, respectively, at a mean follow-up time of
      4.3 months. Bleeding complications occurred in 1 (3%) infant. CONCLUSION:
      Enoxaparin is efficient and safe for infants with congenital heart disease and
      catheter-related arterial thrombosis, possibly representing a valid alternative
      to the currently recommended unfractionated heparin.

PMID- 17554521
TI  - Mid-term follow-up in patients with diaphragmatic plication after surgery for
      congenital heart disease.
AB  - OBJECTIVE: Diaphragmatic palsy (DP) is a rare but severe complication after
      surgery for congenital heart disease. Transthoracic diaphragmatic plication is an
      effective means of treatment for those with respiratory impairment due to DP, but
      little is known about the mid-term effects of diaphragmatic plication. DESIGN: We
      performed a study in 24 patients with history of DP. Diaphragm movement was
      assessed using ultrasound. Patients with DP who were old enough were additionally
      followed-up with lung function and exercise testing. A group of patients with
      similar age, diagnoses and operations served as controls. RESULTS: Ultrasound
      showed that in the majority of cases with history of DP the paralysed diaphragm
      was static, independently of whether it was plicated or not. Patients with DP had
      a more restrictive lung function pattern (VC: 54.3 vs. 76.4% predicted, p<0.001;
      FEV(1): 58.4 vs. 86.2% predicted, p<0.001) and a lower exercise capacity compared
      with the control group (peak VO2: 24.5 vs. 31.3 ml/kg/min, p=0.03). Comparing
      patients with and without plication for DP, only a tendency towards lower lung
      function values in patients after diaphragmatic plication, but no differences
      regarding exercise capacity, could be found. CONCLUSIONS: Our results provide
      evidence that DP is a serious surgical complication with a reduction in lung
      function and exercise capacity, even at mid-term follow-up; however,
      diaphragmatic plication, a useful tool in treating post-surgical DP in children
      with respiratory impairment, seems to be without mid-term risk in terms of
      recovery of phrenic nerve function, lung function values, and exercise capacity.

PMID- 17554522
TI  - Pharmacodynamics and organ storage of hydroxyethyl starch in acute hemodilution
      in pigs: influence of molecular weight and degree of substitution.
AB  - OBJECTIVE: To determine the differential influence of molecular weight and the
      degree of substitution of HES solutions on pharmacodynamics and pharmacokinetics
      including organ storage in a model of acute hemodilution in pigs. DESIGN:
      Prospective controlled randomized animal trial. INTERVENTIONS: After bleeding, 20
      ml/kg, animals were substituted with 6% HES preparations (200/0.62, 200/0.5, and
      100/0.5). MEASUREMENTS AND RESULTS: We did not observe any significant
      differences in the ability to sufficiently achieve plasma volume expansion and
      restoration of macrocirculation, nor maintenance of indicators of
      microcirculation between the groups. Urine production was significantly higher in
      HES-treated animals and highest in animals substituted with HES 100/0.5. Plasma
      clearance was measured under steady-state conditions with significantly reduced
      clearance for the HES 200/0.62 group compared with HES 100/0.5 and HES 200/0.5
      (6.6 vs. 13.2 and 13.9 ml/min; P < or = 0.001), thus being dependent on the
      degree of substitution. Even after only 6 h, the amount of infused HES not
      detectable in either blood or urine was significantly higher in HES 200/0.62
      treated animals (50.7% compared with HES 200/0.5 (28.8%), P = 0.020 and HES
      100/0.5 (28.4%), P = 0.018), with its proportion rising over time. Finally, we
      could demonstrate considerable amounts of all HES solutions being stored in
      liver, kidney, lung, spleen and lymph nodes. CONCLUSIONS: All preparations
      analyzed sufficiently restored macro- and microcirculation; however, for all
      solutions relevant tissue storage of HES was observed after only 6 h.

PMID- 17554523
TI  - Gastric feed intolerance is not increased in critically ill patients with type II
      diabetes mellitus.
AB  - OBJECTIVE: To examine the occurrence of feed intolerance in critically ill
      patients with previously diagnosed type II diabetes mellitus (DM) who received
      prolonged gastric feeding. DESIGN AND SETTING: Retrospective study in a level 3
      mixed ICU. PATIENTS: All mechanically ventilated, enterally fed patients (n =
      649), with (n = 118) and without type II DM (n = 531) admitted between January
      2003 and July 2005. INTERVENTIONS: Patients with at least 72 h of gastric feeding
      were identified by review of case notes and ICU charts. The proportion that
      developed feed intolerance was determined. All patient received insulin therapy.
      RESULTS: The proportion of patients requiring gastric feeding for at least 72 h
      was similar between patients with and without DM (42%, 50/118, vs. 42%, 222/531).
      Data from patients with DM were also compared with a group of 50 patients matched
      for age, sex and APACHE II score, selected from the total non-diabetic group. The
      occurrence of feed intolerance (DM 52% vs. matched non-DM 50% vs. unselected non
      diabetic 58%) and the time taken to develop feed intolerance (DM 62.6 +/- 43.8 h
      vs. matched non-DM 45.3 +/- 54.6 vs. unselected non-diabetic 50.6 +/- 59.5) were
      similar amongst the three groups. Feed intolerance was associated with a greater
      use of morphine/midazolam and vasopressor support, a lower feeding rate and a
      longer ICU length of stay. CONCLUSIONS: In critically ill patients who require
      prolonged enteral nutrition, a prior history of DM type II does not appear to be
      a further risk factor for feed intolerance.

PMID- 17554524
TI  - Prospective evaluation of peripheral venous access difficulty in emergency care.
AB  - OBJECTIVE: Although frequently used and crucial in emergency care, peripheral
      intravenous access has been poorly documented. We examined whether criteria
      related to patient characteristics, underlying disease, devices, or environment
      were associated with difficult peripheral intravenous access. DESIGN AND SETTING:
      Prehospital prospective observational study. PARTICIPANTS AND MEASUREMENTS: For
      each peripheral intravenous access attempt a questionnaire was filled in until
      final success or procedure abandonment. This questionnaire included data on the
      patient, operator, disease, degree of emergency, cannulation, nature of fluid
      infused and the use of gloves, environment, and particular medical observations
      such as recent peripheral intravenous access and chemotherapy. Criteria
      associated with peripheral intravenous access difficulty were identified
      comparing successful and unsuccessful attempts. A total of 671 attempts at
      peripheral intravenous access in 495 patients were studied. RESULTS: The first
      attempt was successful in 368 cases (74%) and unsuccessful in 127 (26%). Final
      success was reported in all cases, including the use of central venous access in
      three cases. No abandonment was reported. Significantly correlated with a
      successful attempt were: the caliber of the catheter (OR 0.793), cannulation
      performed by a nurse specialized in emergency care (OR 3.959), lack of particular
      observations (OR 0.120), and a clean patient (OR 0.505). CONCLUSIONS: Peripheral
      intravenous access was achieved in 99% of the patients in out-of-hospital
      settings. Improved success rate was reported when attempts were performed by a
      nurse specialized in emergency care using a 16- or 18-G catheter in clean
      patients without a particular medical history.

PMID- 17554525
TI  - Genetic and proteomic analyses of CO utilization by Methanosarcina acetivorans.
AB  - Methanosarcina acetivorans, a member of the methanogenic archaea, can grow with
      carbon monoxide (CO) as the sole energy source and generates, unlike other
      methanogens, substantial amounts of acetate and formate in addition to methane.
      Phenotypic analyses of mutant strains lacking the cooS1F operon and the cooS2
      gene suggest that the monofunctional carbon monoxide dehydrogenase (CODH) system
      contributes to, but is not required for, carboxidotrophic growth of M.
      acetivorans. Further, qualitative proteomic analyses confirm a recent report
      (Lessner et al., Proc Natl Acad Sci USA, 103:17921-17926, 2006) in showing that
      the bifunctional CODH/acetyl-CoA synthase (ACS) system, two enzymes involved in
      CO(2)-reduction, and a peculiar protein homologous to both corrinoid proteins and
      methyltransferases are synthesized at elevated levels in response to CO; however,
      the finding that the latter protein is also abundant when trimethylamine serves
      as growth substrate questions its proposed involvement in the reduction of methyl
      groups to methane. Potential catabolic mechanisms and metabolic adaptations
      employed by M. acetivorans to effectively utilize CO are discussed.

PMID- 17554526
TI  - Impaired fear recognition in regular recreational cocaine users.
AB  - INTRODUCTION: The ability to read facial expressions is essential for normal
      human social interaction. The aim of the present study was to conduct the first
      investigation of facial expression recognition performance in recreational
      cocaine users. MATERIALS AND METHODS: Three groups, comprised of 21 cocaine naive
      participants (CN), 30 occasional cocaine (OC), and 48 regular recreational
      cocaine (RC) users, were compared. An emotional facial expression (EFE) task
      consisting of a male and female face expressing six basic emotions (happiness,
      surprise, sadness, anger, fear, and disgust) was administered. Mean percent
      accuracy and latencies for correct responses across eight presentations of each
      basic emotion were derived. Participants were also assessed with the "Eyes task"
      to investigate their ability to recognize more complex emotional states and the
      Symptom CheckList-90-Revised to measure psychopathology. RESULTS: There were no
      group differences in psychopathology or "eyes task" performance, but the RC
      group, who otherwise had similar illicit substance use histories to the OC group,
      exhibited impaired fear recognition accuracy compared to the OC and CN groups.
      The RC group also correctly identified anger, fear, happiness, and surprise, more
      slowly than CN, but not OC participants. The OC group was slower than CN when
      correctly identifying disgust. The selective deficit in fear recognition accuracy
      manifested by the RC group cannot be explained by the subacute effects of
      cocaine, or ecstasy, because recent and less recent users of these drugs within
      this group were similarly impaired. Possible parallels between RC users and
      psychopaths with respect to impaired fear recognition, amygdala dysfunction, and
      etiology are discussed.

PMID- 17554527
TI  - Genotyping of single nucleotide polymorphisms by primer extension reaction and a
      dual-analyte bio/chemiluminometric assay.
AB  - Primer extension reaction (PEXT) is the most widely used approach to genotyping
      of single nucleotide polymorphisms (SNP). It is based on the high accuracy of
      nucleotide incorporation by the DNA polymerase. We propose a dual-analyte
      bio/chemiluminometric method for the simultaneous detection of the PEXT reaction
      products of the normal and mutant allele in a high sample-throughput format. PCR
      amplified DNA fragments that span the SNP of interest are subjected to two PEXT
      reactions using normal and mutant primers in the presence of digoxigenin-dUTP and
      biotin-dUTP. Both primers contain a d(A)30 segment at the 5'-end but differ in
      the final nucleotide at the 3'-end. Under optimized conditions only the primer
      that is perfectly complementary with the interrogated DNA will be extended by DNA
      polymerase and lead to a digoxigenin- or biotin-labeled product. The products of
      the PEXT reactions are mixed, denatured, and captured in microtiter wells through
      hybridization with immobilized oligo(dT) strands. Detection is performed by
      adding a mixture of antidigoxigenin-alkaline phosphatase (ALP) conjugate and a
      streptavidin-aequorin conjugate. The flash-type bioluminescent reaction of
      aequorin is triggered by the addition of Ca2+. ALP is then measured by adding the
      appropriate chemiluminogenic substrate. The method was evaluated by genotyping
      two SNPs of the human mannose-binding lectin gene (MBL2) and one SNP of the
      cytochrome P450 gene CYP2D6. Patient genotypes showed 100% concordance with
      direct DNA sequencing data.

PMID- 17554528
TI  - Origin and release date assessment of environmental plutonium by isotopic
      composition.
AB  - The origin and release date of environmental plutonium have been assessed by the
      measurement of plutonium and americium isotopic composition. The applicability
      and sensitivity of different plutonium isotope ratios, (240)Pu/(239)Pu and
      (241)Pu/(239)Pu measured by inductively coupled plasma sector field mass
      spectrometry and (238)Pu/(239)Pu analysed by alpha spectrometry, have been
      evaluated for origin determination in several types of environmental samples.
      With use of mixing models the contribution of different sources (e.g. global
      fallout or Chernobyl) can be calculated. By the measurement of the
      (241)Am/(241)Pu isotope ratio, the release date (i.e. formation of (241)Pu by
      irradiation) can be estimated in environmental samples, which is an important
      parameter to distinguish recent plutonium release from previous (e.g. Chernobyl)
      emissions.

PMID- 17554529
TI  - Determination of drug-serum protein interactions via fluorescence polarization
      measurements.
AB  - New fast methods for the determination of pharmacokinetic behaviour of potential
      drug candidates are receiving increasing interest. We present a new homogeneous
      method for the determination of drug binding and drug competition for human serum
      albumin and alpha(1)-acid glycoprotein that is amenable to high-throughput
      screening. It is based on selective fluorescent probes and the measurement of
      fluorescence polarization. This leads to decreased interference with fluorescent
      drugs as compared with previously published methods based on similar probes and
      the measurement of fluorescence intensity. The binding of highly fluorescent
      drugs that still interfere with the probes can be measured by simply titrating
      the drugs in a two-component system with the serum protein. The assay may also be
      used to discover strongly binding protein ligands that are interesting for drug
      targeting strategies. Additionally, binding data could be obtained from larger
      libraries of compounds for in silico predictive pharmacokinetics. Figure
      Fluorescence polarization displacement titration of dansylsarcosine (3D-structure
      as insert) bound to human serum albumin (HSA) by naproxene.

PMID- 17554530
TI  - Characterization of imazamox degradation by-products by using liquid
      chromatography mass spectrometry and high-resolution Fourier transform ion
      cyclotron resonance mass spectrometry.
AB  - The photodecomposition of imazamox, a herbicide of the imidazolinone family, was
      investigated in pure water. The main photoproducts from the photolysis were
      followed over time by liquid chromatography mass spectrometry and structures were
      proposed from exact mass determinations obtained by electrospray ionization
      Fourier transform ion cyclotron resonance mass spectrometry. The method comprised
      exact mass determination with better than 0.2 ppm mass accuracy and a
      corresponding structural visualization taking care of respective isotopes with an
      adapted van Krevelen diagram that enabled a systematic approach to the
      characterisation of the elementary composition of each photoproduct. By taking
      advantage of the high resolving power of FT-ICR MS to make precise formula
      assignments, the derived 2D van Krevelen diagram (O/C; H/C; m/z) enabled one to
      structurally differentiate the formed photoproducts and to propose a degradation
      pathway for imazamox.

PMID- 17554531
TI  - Recognition of oxytocin by capillary electrochromatography with monolithic
      tetrapeptide-imprinted polymer used as the stationary phase.
AB  - Using YPLG (Tyr-Pro-Leu-Gly), a tetrapeptide, as the template, an imprinted
      monolithic column was prepared and applied to the selective recognition of
      oxytocin based on the epitope approach and capillary electrochromatography (CEC).
      By optimizing the polymerization solution in terms of functional monomer, cross
      linking reagent, porogen, and imprinted template via CEC evaluations of
      synthesized columns, an imprinted monolith with good recognition capacity (the
      imprinting factors for YPLG and oxytocin were 4.499 and 4.013, respectively) and
      high column efficiency (theoretical plates for YPLG and oxytocin were 22,995
      plates/m and 16,952 plates/m, respectively) was achieved. In addition, the
      effects of various experimental parameters on the recognition of oxytocin,
      including the organic modifier content, the buffer concentration, and the pH
      value, were studied systematically. Furthermore, a mixture of oxytocin and other
      proteins was analyzed using this monolithic CEC column, and oxytocin was eluted
      much more slowly than other large biomolecules, which demonstrated the high
      selective recognition ability of such an imprinted monolith for oxytocin with PLG
      (Pro-Leu-Gly) as the epitope. Figure Separation of a mixture of oxytocin, BSA,
      bovine hemoglobin, ovalbumin, and lysozyme on the open column, the blank
      monolithic column, and the monolithic YPLG-imprinted column.

PMID- 17554532
TI  - Potentially inappropriate medications in the elderly: a French consensus panel
      list.
AB  - OBJECTIVE: To evaluate drug-related problems in the elderly, various lists of
      potentially inappropriate medications have been published in North America.
      Unfortunately, these lists are hardly applicable in France. The purpose of this
      study was to establish a list of inappropriate medications for French elderly
      using the Delphi method. METHOD: A two-round Delphi method was used to converge
      to an agreement between a pool of 15 experts from various parts of France and
      from different backgrounds (five geriatricians, five pharmacologists, two
      pharmacists, two general practitioners, one pharmacoepidemiologist). In round
      one, they were sent a questionnaire based on a literature review listing
      medications and clinical situations. They were asked to comment on the potential
      inappropriateness of the criteria proposed using a 5-point Likert scale (from
      strong agreement to strong disagreement) and to suggest therapeutic alternatives
      and new criteria. In round two, the experts confirmed or cancelled their previous
      answers from the synthesis of the responses of round one. After round two, a
      final list of potentially inappropriate drugs was established. RESULTS: The final
      list proposed 36 criteria applicable to people >/=75 years of age. Twenty-nine
      medications or medication classes applied to all patients, and five criteria
      involved medications that should be avoided in specific medical conditions.
      Twenty-five medications or medication classes were considered with an
      unfavourable benefit/risk ratio, one with a questionable efficacy and eight with
      both unfavourable benefit/risk ratio and questionable efficacy. CONCLUSION: This
      expert consensus should provide prescribers with an epidemiological tool, a
      guideline and a list of alternative therapies.

PMID- 17554533
TI  - Dynamic restacking of Escherichia coli P-pili.
AB  - P-pili of uropathogenic Escherichia coli mediate the attachment to epithelial
      cells in the human urinary tract and kidney and therefore play an important role
      in infection. A better understanding of this mechanism could help to prevent
      bacteria from spreading but also provides interesting insights into molecular
      mechanics for future nanotech applications. The helical rod design of P-pili
      provides an efficient design to withstand hydrodynamic shear forces. The adhesive
      PapG unit at the distal end of the P-pilus forms a specific bond with the
      glycolipid Galabiose. This bond has a potential width Deltax = 0.7 +/- 0.15 nm
      and a dissociation rate K (Off) = 8.0.10(-4) +/- 5.0.10(-4) s(-1). It withstands
      a force of approximately 49 pN under physiological conditions. Additionally, we
      analyzed the behavior of unstacking and restacking of the P-pilus with dynamic
      force spectroscopy at velocities between 200 and 7,000 nm/s. Up to a critical
      extension of 66% of the totally stretched P-pilus, un/re-stacking was found to be
      fully reversible at velocities up to 200 nm/s. If the P-pilus is stretched beyond
      this critical extension a characteristic hysteresis appears upon restacking. This
      hysteresis originates from a nucleation process comparable to a first-order phase
      transition in an undercooled liquid. Analysis of the measurement data suggests
      that 20 PapA monomers are involved in the formation of a nucleation kernel.

PMID- 17554535
TI  - Application of bacteriophages for detection and control of foodborne pathogens.
AB  - The incidence of foodborne infectious diseases is stable or has even increased in
      many countries. Consequently, our awareness regarding hygiene measures in food
      production has also increased dramatically over the last decades. However, even
      today's modern production techniques and intensive food-monitoring programs have
      not been able to effectively control the problem. At the same time, increased
      production volumes are distributed to more consumers, and if contaminated,
      potentially cause mass epidemics. Accordingly, research directed to improve food
      safety has also been taken forward, also exploring novel methods and
      technologies. Such an approach is represented by the use of bacteriophage for
      specific killing of unwanted bacteria. The extreme specificity of phages renders
      them ideal candidates for applications designed to increase food safety during
      the production process. Phages are the natural enemies of bacteria, and can be
      used for biocontrol of bacteria without interfering with the natural microflora
      or the cultures in fermented products. Moreover, phages or phage-derived proteins
      can also be used to detect the presence of unwanted pathogens in food or the
      production environments, which allows quick and specific identification of viable
      cells. This review intends to briefly summarize and explain the principles and
      current standing of these approaches.

PMID- 17554534
TI  - Effects of succinylation on thermal induced amyloid formation in Concanavalin A.
AB  - We have recently shown that upon slight thermal destabilization the legume lectin
      Concanavalin A may undergo two different aggregation processes, leading,
      respectively, to amyloid fibrils at high pH and amorphous aggregates at low pH.
      Here we present an experimental study on the amyloid aggregation of Succinyl
      Concanavalin A, which is a dimeric active variant of Concanavalin. The results
      show that, as for the native protein, the fibrillation process appears to be
      favoured by alkaline pH, far from the isoelectric point of the protein. Moreover,
      it strongly depends on temperature and requires large conformational changes both
      at secondary and tertiary structure level. With respect to the native protein,
      the succinyl derivative forms amyloid fibrils in considerably longer times and
      with a minor exposure of hydrophobic regions. At physiological conditions,
      Concanavalin A still displays a sizeable tendency to form amyloid fibril, while
      the succinyl variant does not. A close correlation was observed between the
      progress of amyloid formation and a narrowing of the tryptophans fluorescence
      emission band, indicating a reduction of protein conformational heterogeneity in
      amyloid fibrils.

PMID- 17554536
TI  - Berardinelli-Seip lipodystrophy.
AB  - Berardinelli-Seip lipodystrophy (BSCL) is a rare, but widely distributed,
      congenital disorder of metabolism. It is characterized by insulin-resistant
      diabetes mellitus and marked deficiency of adipose tissue. The clinical and
      imaging features of the syndrome are mostly due to fat deficiency, diabetes, or
      to manifestations of secondary hyperinsulinemia, which results from the failure
      of the tissues to respond to insulin. Absence of fat may be generalized, or
      depending upon the subtype of the disease, may not affect areas where fat plays a
      mechanical function, such as the palms and soles. Muscles appear hypertrophic. In
      addition, characteristic, but idiopathic, peri-articular lytic lesions may be
      seen in some individuals. The combination of imaging, clinical, and laboratory
      findings is characteristic and readily recognized once the components of the
      syndrome are known.

PMID- 17554537
TI  - Radiographic evaluation of calcaneal fractures: to measure or not to measure.
AB  - OBJECTIVE: The aim of this study was to correlate the functional outcome after
      treatment for displaced intra-articular calcaneal fracture with plain
      radiography. DESIGN: The design was a prognostic study of a retrospective cohort
      with concurrent follow-up. PATIENTS: A total of 33 patients with a unilateral
      calcaneal fracture and a minimum follow-up of 13 months participated. Patients
      filled in three disease-specific questionnaires, graded their satisfaction and
      the indication for an arthrodesis was noted. Standardised radiographs were made
      of the previously injured side and the normal (control) side. Different angles
      and distances were measured on these radiographs and compared with values
      described in the literature. The differences in values in angles and distances
      between the injured and uninjured (control) foot were correlated with the outcome
      of the questionnaires, and the indication for an arthrodesis. RESULTS: None of
      the angles correlated with the disease-specific outcome scores. Of the angles
      only the tibiotalar angle correlated with the VAS (r = 0.35, p = 0.045) and only
      the absolute foot height correlated with the indication for an arthrodesis (odds
      = 0.70, CI = 0.50-0.99). CONCLUSION: In this study the radiographic evaluation
      correlated poorly with the final outcome. Measurements on plain radiographs seem
      not to be useful in determining outcome after intra-articular calcaneal
      fractures.

PMID- 17554538
TI  - Whole-body imaging of the musculoskeletal system: the value of MR imaging.
AB  - In clinical practice various modalities are used for whole-body imaging of the
      musculoskeletal system, including radiography, bone scintigraphy, computed
      tomography, magnetic resonance imaging (MRI), and positron emission tomography
      computed tomography (PET-CT). Multislice CT is far more sensitive than
      radiographs in the assessment of trabecular and cortical bone destruction and
      allows for evaluation of fracture risk. The introduction of combined PET-CT
      scanners has markedly increased diagnostic accuracy for the detection of skeletal
      metastases compared with PET alone. The unique soft-tissue contrast of MRI
      enables for precise assessment of bone marrow infiltration and adjacent soft
      tissue structures so that alterations within the bone marrow may be detected
      before osseous destruction becomes apparent in CT or metabolic changes occur on
      bone scintigraphy or PET scan. Improvements in hard- and software, including
      parallel image acquisition acceleration, have made high resolution whole-body MRI
      clinically feasible. Whole-body MRI has successfully been applied for bone marrow
      screening of metastasis and systemic primary bone malignancies, like multiple
      myeloma. Furthermore, it has recently been proposed for the assessment of
      systemic bone diseases predisposing for malignancy (e.g., multiple cartilaginous
      exostoses) and muscle disease (e.g., muscle dystrophy). The following article
      gives an overview on state-of-the-art whole-body imaging of the musculoskeletal
      system and highlights present and potential future applications, especially in
      the field of whole-body MRI.

PMID- 17554539
TI  - Effect of maximum-tolerated doses and low-dose metronomic chemotherapy on serum
      vascular endothelial growth factor and thrombospondin-1 levels in patients with
      advanced nonsmall cell lung cancer.
AB  - BACKGROUND: Angiogenesis is regulated by a balance of both angiogenic inducers
      and inhibitors. This study was designed to evaluate the effect of both maximum
      tolerated doses (MTD) and low-dose metronomic chemotherapy (LDM) on serum
      vascular endothelial growth factor (VEGF), thrombospondin-1 (TSP1) and VEGFR1
      concentrations in patients with advanced nonsmall cell lung cancer. PATIENTS AND
      METHODS: Forty consecutive patients with advanced stage nonsmall cell lung cancer
      were included in this prospective study. Twenty patients received MTD
      chemotherapy including 75 mg/m2 of cisplatin and 75 mg/m2 of docetaxel on day 1.
      The LDM treatment consisted of cisplatin 25 mg/m2 and docetaxel 25 mg/m2 were
      given to other 20 patients on weeks 1, 2 and 3. Serum levels were prospectively
      measured in serum by ELISA at four times; before chemotherapy and at 1, 2 and 3
      weeks following initiation of chemotherapy. RESULTS: The major finding in this
      study that MTD chemotherapy but not LDM chemotherapy resulted in significant
      changes in VEGFR1 and TSP1 serum levels. Due to the effect of LDM chemotherapy,
      we showed no statistically significant change in patients for all serum VEGF,
      TSP1 and VEGFR1 levels. Similarly, serum VEGF levels did not also change under
      MTD chemotherapy. The MTD chemotherapy induced significant and long-lasting
      increase of TSP1 levels and decrease of VEGFR1 levels that persisted for at least
      3 weeks after the chemotherapy initiation. No significant correlations were found
      between serum VEGF and TSP1 levels in cancer patients treated with both LDM and
      MTD chemotherapy. The circulating angiogenic balance (TSP1/VEGF) is decreased in
      cancer patients (P=0.039). CONCLUSIONS: The continuous/metronomic chemotherapy
      may not achieve a more pronounced antiangiogenic effect than MTD-scheduling
      chemotherapy. Future studies involving a larger number of patients are needed to
      confirm the present findings.

PMID- 17554540
TI  - A new liposomal formulation of Gemcitabine is active in an orthotopic mouse model
      of pancreatic cancer accessible to bioluminescence imaging.
AB  - Despite its rapid enzymatic inactivation and therefore limited activity in vivo,
      Gemcitabine is the standard drug for pancreatic cancer treatment. To protect the
      drug, and achieve passive tumor targeting, we developed a liposomal formulation
      of Gemcitabine, GemLip (O: 36 nm: 47% entrapment). Its anti-tumoral activity was
      tested on MIA PaCa-2 cells growing orthotopically in nude mice. Bioluminescence
      measurement mediated by the stable integration of the luciferase gene was
      employed to randomize the mice, and monitor tumor growth. GemLip (4 and 8 mg/kg),
      Gemcitabine (240 mg/kg), and empty liposomes (equivalent to 8 mg/kg GemLip) were
      injected intravenously once weekly for 5 weeks. GemLip (8 mg/kg) stopped tumor
      growth, as measured via in vivo bioluminescence, reducing the primary tumor size
      by 68% (SD +/- 8%; p < 0.02), whereas Gemcitabine hardly affected tumor size (
      7%; +/- 1.5%). In 80% of animals, luciferase activity in the liver indicated the
      presence of metastases. All treatments, including the empty liposomes, reduced
      the metastatic burden. Thus, GemLip shows promising antitumoral activity in this
      model. Surprisingly, empty liposomes attenuate the spread of metastases similar
      to Gemcitabine and GemLip. Further, luciferase marked tumor cells are a powerful
      tool to observe tumor growth in vivo, and to detect and quantify metastases.

PMID- 17554541
TI  - Invasion and adaptive evolution for individual-based spatially structured
      populations.
AB  - The interplay between space and evolution is an important issue in population
      dynamics, that is particularly crucial in the emergence of polymorphism and
      spatial patterns. Recently, biological studies suggest that invasion and
      evolution are closely related. Here, we model the interplay between space and
      evolution starting with an individual-based approach and show the important role
      of parameter scalings on clustering and invasion. We consider a stochastic
      discrete model with birth, death, competition, mutation and spatial diffusion,
      where all the parameters may depend both on the position and on the phenotypic
      trait of individuals. The spatial motion is driven by a reflected diffusion in a
      bounded domain. The interaction is modelled as a trait competition between
      individuals within a given spatial interaction range. First, we give an
      algorithmic construction of the process. Next, we obtain large population
      approximations, as weak solutions of nonlinear reaction-diffusion equations. As
      the spatial interaction range is fixed, the nonlinearity is nonlocal. Then, we
      make the interaction range decrease to zero and prove the convergence to
      spatially localized nonlinear reaction-diffusion equations. Finally, a discussion
      of three concrete examples is proposed, based on simulations of the microscopic
      individual-based model. These examples illustrate the strong effects of the
      spatial interaction range on the emergence of spatial and phenotypic diversity
      (clustering and polymorphism) and on the interplay between invasion and
      evolution. The simulations focus on the qualitative differences between local and
      nonlocal interactions.

PMID- 17554542
TI  - Event-specific qualitative and quantitative PCR detection of roundup ready event
      GT73 based on the 3'-integration junction.
AB  - With the development of genetically modified organisms, labeling regulations have
      been introduced, which require appropriate detection methods. Event-specific
      qualitative and quantitative polymerase chain reaction (PCR) detection methods
      have become the internationally agreed state-of-art. This paper describes an
      event-specific PCR method for qualitative and quantitative of Roundup Ready
      canola event GT73. The 3'-integration junction was characterized by two methods:
      inverse-PCR and thermal asymmetric interlaced-PCR. In the conventional
      qualitative PCR assay, the event-specific primers designed were confirmed to be
      specific and the limit of detection (LOD) was 0.05% (approximates to ten haploid
      genome copies). In the quantitative TaqMan real-time PCR assay, the LOD and the
      limit of quantification were five and ten haploid genome copies, respectively. In
      addition, for further quantitative detection, a reference molecule which
      contained the canola endogenous gene and event-specific sequence was constructed
      and standard curves were set up. The goodness of the linearity and high
      efficiency of the PCR reaction indicated the usability of the plasmid and the
      established PCR system. Moreover, mixed samples with different GT73 content (6,
      3, 1 and 0.5%) were quantified using the established real-time PCR system to
      evaluate the trueness and precision of the system. The trueness expressed as bias
      varied from 2.00 to 18.00%. The precision expressed as variation coefficient were
      different from 6.40 to 32.95%. From above results, we believed that the
      established event-specific qualitative and quantitative PCR systems for GT73 in
      this study were acceptable and suitable for genetic modified canola detection.

PMID- 17554543
TI  - Transgenic tobacco plants overexpressing the heterologous lea gene Rab16A from
      rice during high salt and water deficit display enhanced tolerance to salinity
      stress.
AB  - The full length Rab16A, from the indica rice Pokkali, was introduced into tobacco
      by Agrobacterium-mediated transformation. The transgene was stably integrated
      into the genome and they originated from different lines of integration.
      Expression of Rab16A transcript driven by its own promoter (stress inducible) in
      T2 progenies, only when triggered by salinity/ABA/PEG (Polyethylene glycol)
      mediated dehydration, but not at the constitutive level, led to the stress
      induced accumulation of RAB16A protein in the leaves of transgenic plants. The
      selected independent transgenic lines showed normal growth, morphology and seed
      production as the WT plants without any yield penalty under stress conditions.
      They exhibited significantly increased tolerance to salinity, sustained growth
      rates under stress conditions; with concomitant increased osmolyte production
      like reducing sugars, proline and higher polyamines. They also showed delayed
      development of damage symptoms with better antioxidative machinery and more
      favorable mineral balance, as reflected by reduced H2O2 levels and lipid
      peroxidation, lesser chlorophyll loss as well as lesser accumulation of Na+ and
      greater accumulation of K+ in 200 mM NaCl. These findings establish the potential
      role of Rab16A gene in conferring salt tolerance without affecting growth and
      yield, as well as pointing to the fact that the upstream region of Rab16A behaves
      as an efficient stress-inducible promoter. Our result also suggests the
      considerable potential of Group 2 lea genes as molecular tools for genetic
      engineering of plants towards stress tolerance.

PMID- 17554544
TI  - Increased number of apoptotic endothelial cells in bladder of interstitial
      cystitis patients.
AB  - In this study, we aimed to investigate possible abnormality of bladder
      endothelial cells in interstitial cystitis patients by detecting morphological
      changes such as apoptosis in bladder endothelial cells. A bladder biopsy specimen
      was collected from interstitial cystitis patients immediately after
      hydrodistension therapy. The patients were classified into two groups on the
      basis of their predominant symptom, one group of patients with bladder pain and
      another group of patients with urinary urgency. Dissociated cells from the biopsy
      specimen were analyzed by flow cytometry after staining with Annexin V and an
      anti-CD105 antibody. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end
      labeling (TUNEL) and electron microscopy were performed to confirm morphologic
      changes indicative of apoptosis. The percentage of Annexin V binding, an early
      apoptosis marker, was significantly higher in bladder endothelial cells from
      interstitial cystitis patients with pain [median 24.7% (range 15.1-77.2), n = 20,
      P < 0.01) than that from interstitial cystitis patients with urinary urgency
      [9.3% (range 0.7-19.11) n = 17) or control patients [1.5% (range 0.8-9.1), n =
      7]. TUNEL staining showed apoptotic cells in microvascular endothelial cells but
      not in the endothelial cells of a venule. By electron microscopy, endothelial
      cells showed morphological changes indicative of apoptosis such as nuclear
      fragmentation. Our results indicate that increased apoptosis of bladder
      microvascular endothelial cells may play an important role in the pathogenesis of
      interstitial cystitis accompanied by bladder pain.

PMID- 17554545
TI  - Congenital pancreatic cyst arising from occlusion of the pancreatic duct.
AB  - Congenital pancreatic cysts, particularly solitary cysts, are rare causes of
      abdominal masses in newborns. The etiology of these cysts is unknown and they can
      vary in location within the pancreas. We present a novel case of an infant with a
      solitary congenital cyst of the pancreatic duct, itself, as a result of occlusion
      of the pancreatic duct. Solitary congenital pancreatic cysts are a rare cause of
      abdominal masses in infants. We recently evaluated a 7-week-old infant with
      progressive abdominal distension since birth. This child was found to have a
      large solitary pancreatic cyst. This cyst resulted from occlusion of the main
      pancreatic duct at the level of the ampulla resulting in cystic degeneration of
      the pancreatic duct. Based on our review of the literature we believe this is the
      first documented case of such a cyst.

PMID- 17554546
TI  - An assessment of the incidence of fistula-in-ano in four countries of the
      European Union.
AB  - BACKGROUND AND AIMS: In spite of its long history, fistula-in-ano is generally
      considered to be relatively uncommon. Nevertheless, no comprehensive analysis of
      its incidence in developed countries is available. Our goal was to determine the
      actual incidence of fistula-in-ano based on the study of incidence in four
      countries of the European Union (EU). MATERIALS AND METHODS: We performed a
      search of hospital inpatient databases in five different countries. We obtained
      valid data from four European countries, namely, England (UK; Hospital Episodes
      Statistics), Germany (German hospitals' databases), Italy (Scheda di Dimissione
      Ospedaliera), and Spain (Conjunto Minimo Basico de Datos by Insalud-Spanish
      National Health Institute). RESULTS: The incidence of fistula-in-ano varied among
      the different populations in the EU. In the four countries examined, it ranged
      from 1.04 per 10,000/year in Spain to 2.32 per 10,000/year in Italy. A
      statistical comparison of rates from the different countries studied gives a
      confidence interval from 1.20 up to 2.80. The population that we studied
      represents almost 51% of the total population of the EU. CONCLUSION: This study
      attempts to determine the actual incidence of fistula-in-ano in the European
      Community, which was previously uncertain despite its major negative effects on
      quality of life and the high cost of treatment. Our findings indicate that the
      incidence of fistula-in-ano in the four countries of the EU studied is
      significantly higher than that in the only previously published report of the
      incidence of fistula-in-ano in Europe. Nevertheless, our findings confirm the
      general perception that fistula-in-ano is a relatively uncommon disease.

PMID- 17554547
TI  - The relationship between shoulder pain and damage to the cervical plexus
      following neck dissection.
AB  - The aim of our study was to evaluate the relationship between shoulder pain and
      damage to the cervical plexus after neck dissection. The study was performed
      prospectively on 34 neck sides of 17 patients with laryngeal cancer who underwent
      laryngectomy plus bilateral selective neck dissection (II, III, IV, +/- VI) at
      the Department of Otorhinolaryngology of Uludag University between December 2003
      and October 2004. The cervical plexus was protected on one side of the neck and
      sacrificed on the other, while the accessory nerve was spared on both sides. The
      degree of sensorial innervation of the cervical plexus and shoulder pain were
      evaluated in the preoperative period and postoperatively at 2 weeks, 1 month, 3
      months, and 6 months. Data obtained from both sides of the neck were compared.
      Sensory reception scores were statistically higher in the neck sides in which the
      cervical plexus was spared than in those where the plexus was sacrificed (P <
      0.05). However, the degree of shoulder pain was similar on both sides of the neck
      (P > 0.05). Damage to the cervical plexus during neck dissection causes loss of
      sensorial innervation of the neck, but sacrificing the cervical plexus during
      selective neck dissection has no negative effect on shoulder pain.

PMID- 17554548
TI  - Demonstration of a radiation-induced bystander effect for low dose low LET beta
      particles.
AB  - Radiation-induced bystander mutagenesis at a relatively low dose range was
      investigated using low LET beta-particles in a three-dimensional cell culture
      model. CHO cells were labeled with 0, 0.5, 1.0 or 5.0 muCi tritiated thymidine
      ((3)HdTTP) for 12 h and subsequently incubated with A(L) cells for 24 h at 11
      degrees C. The cell mixture was centrifuged to produce a spheroid of 4 x 10(6)
      cells of which there was five times more A(L) than CHO cells. The short-range
      beta-particles emitted by (3)HdTTP result in self-irradiation of labeled CHO
      cells, thus biological effects on neighboring A(L) cells can be attributed to the
      bystander response. To evaluate such response, non-labeled bystander A(L) cells
      were isolated from among labeled CHO cells and studied independently for survival
      and mutagenesis. Treatment of CHO cells with (3)HdTTP resulted in a dose
      dependent increase in bystander mutation incidence among neighboring A(L) cells
      compared to controls. In addition, multiplex PCR analysis revealed the types of
      mutants to be significantly different from those of spontaneous origin. These
      data provide evidence that low dose low LET radiation can induce bystander
      mutagenesis in a three-dimensional model. The results of this study will address
      the relevant issues of actual target size and radiation quality, and are likely
      to have a significant impact on our current understanding of radiation risk
      assessment.

PMID- 17554549
TI  - Non-linear function model of voice pitch dependency on physical and mental load.
AB  - The present work describes that under increasing physical load the voice
      fundamental frequency (voice pitch) remains on a given level as long as the
      physical load is well tolerated by the subject, whereas heart rate and blood
      pressure continuously increase during increasing physical load. This voice pitch
      level was compared to voice pitch levels under mental load. Using a word
      recognition system, 11 well trained, young male subjects had to solve 2 moderate
      mental load tasks. Before, during and after each task, there were structured
      relaxation phases. The physical load protocol was a standard bicycle stress test.
      In each protocol phase the subjects had to count from 1 to 10 in order to provide
      a standardized speech sample. Heart rate and blood pressure were recorded in all
      phases. Voice frequency was at average 106 +/- 5.2 Hz in the relaxation phases
      ('rest level') and was increased under mental load (115.9 +/- 5.7 Hz, Pillais-P =
      0.037). During physical stress testing, voice pitch remained unchanged
      ('tolerated load level') between 100 and 200 W (117.4 +/- 4.8 Hz) and increased
      shortly before physical exhaustion ('exhaustion level', 275-350 W, 142.9 +/- 5.6
      Hz, Pillais-P = 0.007). In contrast, heart rate and blood pressure increased
      continuously with the physical load. Three voice pitch levels could be verified
      also individually for each subject. For the practical monitoring of emotional
      stress the individual anchor frequencies for these levels must be assessed. These
      data indicate that the relationship between both types of load and voice pitch is
      non-linear with multiple plateaus and transition functions between them.

PMID- 17554550
TI  - Tensile and compressive stresses in tracheids are induced by swelling based on
      geometrical constraints of the wood cell.
AB  - Plants are able to pre-stress their tissues in order to actuate their organs.
      Here, we demonstrate with two tissue types of the secondary xylem of conifers
      (normal wood and compression wood of spruce (Picea abies)) that either tensile or
      compressive stresses can develop in the longitudinal direction during the
      swelling of the cell wall. This dramatic difference appears to be due mostly to
      differences in cell geometry and cellulose fibril orientation. A mechanical model
      was developed to demonstrate swelling experiments with the help of sodium iodide
      experiments. The reversal of longitudinal extension can be predicted, based on
      the orientation of the (nearly inextensible) cellulose fibrils and the shape of
      the cell.

PMID- 17554551
TI  - Cell wall extensibility during branch formation in the xanthophycean alga
      Vaucheria terrestris.
AB  - In the tip-growing filamentous cell of the xanthophycean alga Vaucheria
      terrestris sensu Gotz, a new growing tip develops in the non-growing, cylindrical
      region of the cell that was exposed by local illumination. The present study
      examined changes in the strength and extensibility of the cell wall of the new
      growing tip and in the matrix components of the inner surface of the cell wall.
      The internal pressure required to rupture the cell walls decreased remarkably
      during the early to middle stages of growing tip development, but the cell wall
      hardly extended before rupture. In contrast, during the middle and late stages of
      development, cell walls were extended by internal pressure. Atomic force
      microscopy revealed that protease-resistant, fine granular matrix components were
      present only at the apical portion of a normal growing tip, and were absent in
      the non-growing cylindrical region. In the early and middle stages of new growing
      tip development, these matrix components appeared in the cell walls in patches.
      These results suggest that first cell wall strength decreases and then cell wall
      extensibility increases in the development of new growing tips, and that protease
      resistant, fine granular matrix components may be involved in rendering a cell
      wall extensible.

PMID- 17554552
TI  - A degradation product of the salicylic acid pathway triggers oxidative stress
      resulting in down-regulation of Bacillus subtilis biofilm formation on
      Arabidopsis thaliana roots.
AB  - Bacillus subtilis, a plant growth promoting rhizobacteria (PGPR), induces growth
      response and protection against pathogenic organisms through colonization and
      biofilm formation on the Arabidopsis thaliana root surface. In the current
      investigation, we utilized various Arabidopsis defense pathway mutants in a
      series of studies and showed that the plants recognize B. subtilis by a chemical
      dependent cascade, which is independent of the salicylic acid (SA), jasmonic acid
      (JA), or ethylene pathways. These experiments revealed the importance of root
      surface chemistry in colonization and biofilm formation by B. subtilis. It was
      found that B. subtilis FB17 could not form biofilms on the roots of NahG, a
      transgenic Arabidopsis line for salicylate hydroxylase that produces catechol as
      the degradation product of SA. These findings suggest that catechol may play a
      direct role in inhibiting B. subtilis FB17 biofilm formation on the NahG root
      surface, possibly through induction of reactive oxygen species (ROS) in the
      roots. Using both in vitro microtitre plate and in planta assays we confirmed
      that catechol inhibited biofilm formation, but not the planktonic growth, of B.
      subtilis. Inhibition of biofilm formation was shown to be the result of a
      physiological response by B. subtilis to the presence of catechol, which resulted
      in the down-regulation of transcription of the yqxM-sipW-tasA and epsA-O operons,
      both of which are required for biofilm formation by B. subtilis. These data
      indicate that the suppression of biofilm formation on NahG plants was strongly
      influenced by the root-derived catechol production through ROS-mediated down
      regulation of B. subtilis biofilm genes.

PMID- 17554553
TI  - Role of hydroxyproline-rich glycoproteins in resistance of pearl millet against
      downy mildew pathogen Sclerospora graminicola.
AB  - Hydroxyproline-rich glycoproteins (HRGPs) are important plant cell wall
      components involved in plant defense response to pathogen attack. In the present
      study, a resistant pearl millet (Pennisetum glaucum) cultivar, IP18292, was
      compared with a susceptible cultivar, 7042S, to investigate the contribution of
      HRGPs in the successful defense against the phytopathogenic oomycete S.
      graminicola. Northern hybridization using MeHRGP cDNA, a heterologous probe from
      cassava, indicated steady accumulation of HRGP transcripts, from 2 h.p.i. onwards
      with a maximum at 6 h.p.i., in the resistant cultivar. This is followed by HRGPs
      accumulation at about 8 h.p.i. as revealed by Western-blot analysis.
      Immunocytochemical localization by tissue printing and confocal
      immunofluorescence microscopy indicated cell walls of parenchymatic cells and the
      vascular tissue of coleoptile as sites of HRGP deposition. In vitro studies in
      the presence of horseradish peroxidase and H2O2 showed cross-linking of pearl
      millet HRGPs, which occurred parallel to isodityrosine accumulation. Inducible
      high isodityrosine content was also observed in vivo in the resistant cultivar.
      Here, H2O2 was found to accumulate as twin burst at 1 and 6 h.p.i., whereas in
      the susceptible cultivar only an early single peak was detectable. Moreover, the
      amount of hydroxyproline in HRGPs was about twice as high in the resistant as in
      the susceptible cultivar. These results suggest that cell wall strengthening in
      S. graminicola-infected resistant pearl millet is brought about by a combination
      of polypeptide cross-linking of isodityrosine as well as by the high content of
      hydroxyproline in HRGPs, and H2O2, in contrast to the susceptible plant.

PMID- 17554554
TI  - The olig family: phylogenetic analysis and early gene expression in Xenopus
      tropicalis.
AB  - The olig genes form a small subfamily of basic helix-loop-helix transcription
      factors. They were discovered in 2000 as genes required for oligodendrocyte
      lineage specification. Since then, olig genes have been identified in various
      vertebrate species and corresponding sequences accumulated within genomic
      databases. Until now, three groups of olig genes have been characterized. Our
      phylogenetic analysis demonstrates the existence of a fourth group, which we
      named olig4. Genes of the four olig groups are present in actinopterygians and
      amphibians, whereas mammals only possess olig1, 2, and 3. We also found one olig
      gene in hemichordates, urochordates, and cephalochordates. Our expression study
      during Xenopus tropicalis embryogenesis shows that the four olig genes have very
      distinct expression patterns. Olig1 is very faintly expressed before the tadpole
      stage, whereas olig2, 3, and 4 are expressed from the gastrula stage onward. The
      olig3 expression during neurulation suggests a role in early anteroposterior
      patterning of the brain. All these results indicate that olig genes are involved
      in several developmental processes during early development.

PMID- 17554555
TI  - Ki-67 expression in primary breast carcinomas and their axillary lymph node
      metastases: clinical implications.
AB  - Proliferative activity of tumour cells assessed by immunohistochemical Ki-67
      expression is one of several prognostic indicators in breast cancer. The major
      objective of this study was to investigate the prognostic impact of Ki-67
      proliferative activity in the axillary lymph node metastases and in the matched
      primary breast carcinoma from 194 patients. There was a statistically significant
      up-regulation of Ki-67 protein in the metastatic deposit compared to where the
      primary tumour was found (p = 0.001). A low Ki-67 index in both the primary and
      the metastatic tumours was a favorable prognostic factor. A high index in both
      primary and metastatic lesion and an up-regulation from a low index in the
      primary tumour to a high index in the metastatic deposit represented an
      unfavorable prognostic factor. Multivariate analysis showed that Ki-67 expression
      in the metastases was a superior independent prognostic factor of clinical
      outcomes compared to that in the primary tumours. Ki-67 expression in > or =10%
      of carcinoma cells in the primary tumours and > or =15% in the nodal metastases
      seems to be optimal cut-off levels. Ki-67 is of value as an independent
      prognostic factor in breast cancer.

PMID- 17554556
TI  - Unexpected diagnosis of cystic fibrosis at liver biopsy: a report of four
      pediatric cases.
AB  - We report here four cases of pediatric patients in whom the diagnosis of cystic
      fibrosis was made only after the histological examination of a liver specimen
      obtained by biopsy (three cases) or at autopsy (one case). There were two boys
      and two girls, aged 13 months to 7.5 years. None had a personal or familial
      history suggestive of cystic fibrosis. One patient, presenting with myocardial
      lesion and hepatomegaly, died of heart failure; at autopsy, the liver showed a
      typical aspect of focal biliary cirrhosis. In the three other cases, liver
      disease was the only manifestation of cystic fibrosis at the time of diagnosis.
      Liver biopsy examination showed focal biliary cirrhosis in one case and massive
      steatosis in two. In all four cases, the diagnosis was confirmed by the existence
      of known pathogenic mutations in the CFTR gene. The evolution was variable; one
      patient had progressive liver disease with severe portal hypertension after 7
      years; another one had lung complications after 1 year. In conclusion, our
      experience recalls that the diagnosis of cystic fibrosis must be considered in
      children presenting with unexplained liver disease; its confirmation by molecular
      techniques makes it possible to set up an appropriate follow-up.

PMID- 17554557
TI  - Human pheochromocytomas show reduced p27Kip1 expression that is not associated
      with somatic gene mutations and rarely with deletions.
AB  - Pheochromocytomas are neuroendocrine tumors arising in the neural crest-derived
      chromaffin cells of the adrenal gland or in extra-adrenal sympathetic ganglia
      (paragangliomas). In a rat model of multiple endocrine neoplasia (MEN), absence
      of functional p27Kip1 protein predisposes to pheochromocytoma and paraganglioma
      development. As no data is available regarding the involvement of p27Kip1 in
      human pheochromocytoma and/or paraganglioma, we set out to determine the
      expression pattern of p27Kip1 in those tumor types. A panel of 25
      pheochromocytomas and 23 paragangliomas was collected. Two pheochromocytomas were
      from MEN2 patients. The paragangliomas included 15 tumors that developed at the
      carotid bifurcation, three in the jugulo-tympanic area, and five at other sites.
      Except for the MEN2 cases, all others were apparently sporadic.
      Immunohistochemistry for p27Kip1 and the proliferation marker Ki67 was performed.
      We found that p27Kip1 expression is reduced/lost in 56% of pheochromocytomas, but
      only in 18.1% of paragangliomas. Downregulation of p27Kip1 was not associated
      with increased proliferation. Cases showing reduced/lost p27Kip1 expression were
      screened for the presence of somatic mutations in CDKN1B (p27Kip1) and for
      allelic imbalance at the p27Kip1 locus. Three cases had allelic imbalance but
      none had mutations. In conclusion, pheochromocytomas display extreme
      reduction/loss of p27Kip1 expression at high frequency.

PMID- 17554558
TI  - Hepatoportal venopathy due to disseminated Mycobacterium avium complex infection
      in a child with IFN-gamma receptor 2 deficiency.
AB  - The control of intracellular microorganisms such as mycobacteria is largely
      dependent on the adaptive immune response, specifically the interaction of T
      helper cells and antigen presenting cells such as macrophages. The interferon
      gamma (IFN-gamma) pathway activation is crucial for containment and killing of
      mycobacteria, as evidenced by the fact that defects in this pathway often result
      in profound infections with both tuberculous and non-tuberculous mycobacteria. We
      herein report a case of a child with autosomal recessive IFN-gamma receptor 2
      (IFN-gammaR2) deficiency who developed hepatic venopathy secondary to
      disseminated Mycobacterium avium complex (MAC) infection.

PMID- 17554560
TI  - Urethral prolapse misdiagnosed as vaginal bleeding in a premenarchal girl.
AB  - We report on a 10-year-old girl who was presented to the Emergency Department
      with a 3-day history of "vaginal bleeding", the cause of which was determined to
      be urethral prolapse. Urethral prolapse occurs when the urethra mucosa evaginates
      beyond the urethral meatus. This uncommon condition in prepubescent girls should
      not be confused with other causes of peri-vaginal bleeding, the most importantly
      being sexual abuse.

PMID- 17554561
TI  - Effect of galactose free formula on galactose-1-phosphate in two infants with
      classical galactosemia.

PMID- 17554559
TI  - Submucosal connective tissue-type mast cells contribute to the production of
      lysophosphatidic acid (LPA) in the gastrointestinal tract through the secretion
      of autotaxin (ATX)/lysophospholipase D (lysoPLD).
AB  - Lysophosphatidic acid (LPA) is involved in a broad spectrum of biological
      activities, including wound healing and cancer metastasis. Autotaxin (ATX),
      originally isolated from a melanoma supernatant as a tumor cell motility
      stimulating factor, has been shown to be molecularly identical to
      lysophospholipase D (lysoPLD), which is the main enzyme in the production of LPA.
      Although ATX/lysoPLD is known to be widely expressed in normal human tissues, the
      exact distribution of ATX-producing cells has not been fully investigated. In
      this study, we evaluated ATX/lysoPLD expression by immunohistochemical staining
      using a rat anti-ATX mAb in the human gastrointestinal tract and found that
      submucosal mast cells (MC) highly expressed this enzyme. This was confirmed by
      immunofluorescent double staining using mAbs to tryptase and chymase. Then, we
      isolated MC from human gastric tissue by an immunomagnetic method using CD117
      microbeads and showed that a subpopulation of CD203c-positive MC showed positive
      staining for intracellular ATX/lysoPLD on flowcytometry. This was confirmed by
      Western blotting of the isolated cells. Moreover, a significant level of
      ATX/lysoPLD release could be detected in the culture supernatants of human MC by
      Western blot analysis. Our data suggest that submucosal MC play significant roles
      in various aspects of pathophysiology in the gastrointestinal tract by locally
      providing bioactive LPA through the production of ATX/lysoPLD.

PMID- 17554562
TI  - Determination of Rhipicephalus spp. as vectors for Babesia ovis in Iran.
AB  - The tick-borne diseases of livestock constitute a complex of several diseases
      with different etiological agents, such as protozoa, rickettsia, bacteria, and
      viruses. One problem discussed in protozoan infection is the determination and
      characterization of the transmitter agent. Because many analyses were performed
      with the salivary gland smears using the methyl-green-pyronin staining method or
      the Feulgen staining method, the transfer vector remains unanswered in some
      cases. The aim of this study is to recognize Babesia ovis in the salivary gland
      of Rhipicephalus spp. using polymerase chain reaction (PCR). Deoxyribonucleic
      acid (DNA) was isolated from 269 salivary gland of Rhipicephalus spp. (108 R.
      bursa, 87 R. turanicus, 74 R. sanguineus) collected from sheep with suspected to
      babesiosis. The isolated DNA was then analyzed with the primers derived from the
      hypervariable region V4 of 18S ribosomal ribonucleic acid (rRNA) of the Babesia
      species. For the specificity of the PCR product and discriminating from Babesia
      motasi and Babesia crassa, nested PCR and restriction fragment length
      polymorphism was performed. As positive control for the DNA extraction procedure,
      the DNA was analyzed with the common primers designed from the 18S rRNA of the
      Ticks (Rhipicephalus, Hyalomma, Haemophysalis, Dermacentor, Ixodes, Boophilus).
      B. ovis was detected in salivary gland of 18.5% R. bursa, 9.1% R .turanicus, and
      8.1% R. sanguineus, respectively.

PMID- 17554563
TI  - Evaluation of the SNP tagging approach in an independent population sample--array
      based SNP discovery in Sami.
AB  - Significant efforts have been made to determine the correlation structure of
      common SNPs in the human genome. One method has been to identify the sets of
      tagSNPs that capture most of the genetic variation. Here, we evaluate the
      transferability of tagSNPs between populations using a population sample of Sami,
      the indigenous people of Scandinavia. Array-based SNP discovery in a 4.4 Mb
      region of 28 phased copies of chromosome 21 uncovered 5,132 segregating sites,
      3,188 of which had a minimum minor allele frequency (mMAF) of 0.1. Due to the
      population structure and consequently high LD, the number of tagSNPs needed to
      capture all SNP variation in Sami is much lower than that for the HapMap
      populations. TagSNPs identified from the HapMap data perform only slightly better
      in the Sami than choosing tagSNPs at random from the same set of common SNPs.
      Surprisingly, tagSNPs defined from the HapMap data did not perform better than
      selecting the same number of SNPs at random from all SNPs discovered in Sami.
      Nearly half (46%) of the Sami SNPs with a mMAF of 0.1 are not present in the
      HapMap dataset. Among sites overlapping between Sami and HapMap populations, 18%
      are not tagged by the European American (CEU) HapMap tagSNPs, while 43% of the
      SNPs that are unique to Sami are not tagged by the CEU tagSNPs. These results
      point to serious limitations in the transferability of common tagSNPs to capture
      random sequence variation, even between closely related populations, such as CEU
      and Sami.

PMID- 17554564
TI  - The influence of stage-dependent dispersal on the population dynamics of three
      amphipod species.
AB  - In metapopulations, the maintenance of local populations can depend on source
      sink dynamics, where populations with positive growth rate seed populations with
      negative growth rate. The pattern and probability of successful dispersal among
      habitats can therefore be crucial in determining whether local populations will
      become rare or increase in abundance. We present here data on the dispersal
      strategy and population dynamics of three marine amphipods living in pen shells
      (Atrina rigida) in the Gulf of Mexico. The three amphipod species in this study
      disperse at different life stages. Neomegamphopus hiatus and Melita nitida
      disperse as adults, while Bemlos unicornis disperses as juveniles. The two
      species that disperse as adults have the highest initial population sizes when a
      new shell becomes available, likely caused by the arriving females releasing
      their brood into these recently occupied shells. This dispersal pattern results
      in initially higher population growth, but fewer occupied shells, as noted by
      their clumped distribution. In contrast, the species that disperses as juveniles
      accumulates more slowly and more evenly across habitats, eventually dominating
      the other two in terms of numerical abundance. The metapopulation dynamics of the
      three species seems to be highly dependent on the life history stage involved in
      dispersal.

PMID- 17554565
TI  - Molecular mechanism of edema formation in nephrotic syndrome: therapeutic
      implications.
AB  - Sodium retention and edema are common features of nephrotic syndrome that are
      classically attributed to hypovolemia and activation of the renin-angiotensin
      aldosterone system. However, numbers of clinical and experimental findings argue
      against this underfill theory. In this review we analyze data from the literature
      in both nephrotic patients and experimental models of nephrotic syndrome that
      converge to demonstrate that sodium retention is not related to the renin
      angiotensin-aldosterone status and that fluid leakage from capillary to the
      interstitium does not result from an imbalance of Starling forces, but from
      changes of the intrinsic properties of the capillary endothelial filtration
      barrier. We also discuss how most recent findings on the cellular and molecular
      mechanisms of sodium retention has allowed the development of an efficient
      treatment of edema in nephrotic patients.

PMID- 17554567
TI  - Laboratory diagnosis of Mycoplasma pneumoniae respiratory tract infections in
      children.

PMID- 17554566
TI  - Molecular regulation of kidney development: is the answer blowing in the Wnt?
AB  - Development of the metanephric kidney is a complicated process regulated by
      reciprocal signals from the ureteric bud and the metanephric mesenchyme that
      regulate tubule formation and epithelial branching morphogenesis. Over the past
      several years, several studies have suggested that Wnt signaling is involved in
      multiple aspects of normal kidney development as well as injury response and
      cancer progression. We will review these data here.

PMID- 17554568
TI  - Flucloxacillin treatment of Staphylococcus aureus meningitis.
AB  - In this paper, we aimed to evaluate the efficacy of flucloxacillin treatment of
      meningitis caused by methicillin-sensitive Staphylococcus aureus. We identified
      33 patients with meningitis due to S. aureus; eight had community-acquired
      meningitis and 25 had neurosurgical meningitis. Six of the eight patients with
      community-acquired meningitis were cured. Eighteen of the 22 patients treated
      with flucloxacillin were cured without relapse (86%, 95%CI 65-97%) and their
      cerebrospinal fluid (CSF) cultures were sterile after a median of 3 days of
      treatment. The cure rate for 12 patients who also received an additional
      antibiotic at the outset of treatment was 75% (95%CI 43-95%). This was not
      different to the cure rate for the ten patients who received flucloxacillin alone
      90% (95%CI 56-100%). We conclude that flucloxacillin is an effective treatment
      for meningitis caused by S. aureus.

PMID- 17554569
TI  - Community-acquired pneumonia: aetiologic changes in a limited geographic area. An
      11-year prospective study.
AB  - The aim of this study is to describe the changes in the aetiology of hospitalised
      patients with community-acquired pneumonia (CAP) during an 11-year observational
      period in a limited geographic area. Eight hundred and one (801) adult patients
      with CAP hospitalised were included. The patients were divided into three groups
      according to the time of presentation. Comprehensive microbiological laboratory
      tests were performed and differences in aetiology were analysed. In 228 patients
      (31%), a pathogen was detected, with Coxiella burnetii being the most common
      (20.1%). Significant variations in the prevalence of Chlamydophila pneumoniae
      were found between groups but not in other pathogens. In conclusion, long-term
      epidemiological studies may contribute to the knowledge of actual CAP aetiology.

PMID- 17554570
TI  - Evaluation of a novel rapid one-step monoclonal chromatographic immunoassay for
      detection of Helicobacter pylori in stool from children.
AB  - A new rapid office-based one-step monoclonal immunoassay (RAPID Hp StAR,
      DakoCytomation, Cambridge, UK) for detection of Helicobacter pylori antigen in
      stool was evaluated in children against invasive diagnostic methods and compared
      to the results of a monoclonal EIA targeting the same antigen (Amplified IDEIA Hp
      StAR, DakoCytomation, Cambridge, UK). Coded stool samples from 118 symptomatic
      children (0.3-18.8 years) were investigated prior to any anti-H. pylori therapy.
      Fifty-four children were H. pylori infected defined by positive culture and/or
      two other positive tests ((13)C-urea breath test, histology, rapid urea test),
      the remaining 64 children showed concordant negative results. Thirty-four
      infected children (4.8-17.8 years) were monitored with (13)C-urea breath test
      (five remained positive) and stool test 6-8 weeks after anti-H. pylori therapy.
      The immunoassays were independently read by two investigators. The monoclonal EIA
      showed excellent sensitivity and specificity before (98% and 100%, respectively)
      and after therapy (100%; 96.2%). The rapid immunoassay was invalid for technical
      reasons in nine samples (5.9%). The two observers agreed in 31 positive and 93
      negative results, but had discordant results in 17 samples (11.2%). Overall, the
      rapid test showed a poor sensitivity (63.8%-71.1%), but a good specificity (91.1%
      96.2%) before treatment. We conclude that the new office based monoclonal enzyme
      immunoassay for diagnosis of H. pylori should be modified to improve sensitivity,
      inter-observer-variability and some technical problems. In contrast, the
      monoclonal EIA stool test is highly reliable, both pre- and post therapy, and
      equivalent to the (13)C-urea breath test.

PMID- 17554571
TI  - Murine typhus in Cyprus: 21 paediatric cases.
AB  - The aim of this article is to present the manifestations of Rickettsia typhi
      infection in childhood. Twenty-one children under 15 years of age were
      hospitalised in the Department of Paediatrics of the Archbishop Makarios Hospital
      in Nicosia, Cyprus, from 2000 to 2006 with Rickettsia typhi infection. Ten of
      them were boys and 11 were girls. The median age was eight years (range four to
      13 years). The most common clinical features were fever (100%) and rash (57%).
      Lymphadenopathy, usually cervical, was also a frequent finding (37%). Severe
      headache was rather infrequent (29%). Splenomegaly or hepatomegaly were less
      frequent findings (24% and 10%, respectively). Mild elevation of liver enzymes
      (AST and ALT elevated >1-fold in 81% and 75%, respectively) was the most frequent
      laboratory finding. Thrombocytopenia (28%) and leucopenia (17%) were less
      frequent. Nearly half of the patients (10/21) came from four neighbouring
      villages, where most residents work in agriculture. All of the children were
      treated with appropriate antibiotic regimens and had complete recovery.
      Rickettsia typhi infection should be considered in the differential diagnosis of
      children who present during the summer or early autumn months with prolonged
      fever and rash with or without lymphadenopathy.

PMID- 17554572
TI  - Reverse ELISA for the detection of anti West Nile virus IgG antibodies in humans.
AB  - We have developed a specific reverse ELISA to investigate the potential of the
      domain III of the West Nile virus envelope protein to detect virus-specific
      antibodies. For this purpose, the domain III antigen was expressed in Escherichia
      coli, refolded and directly labelled with peroxidase. By mixing serum samples
      with the enzyme-labelled antigen, immune complexes will form that are
      simultaneously recognized by rheumatoid factor coated microtiter plates. Specific
      antibodies to the domain III were found in 160 out of 206 sera of patients with
      neutralising antibodies to West Nile virus (77.6% sensitivity). The antigen
      differentiated reliably between sera of West Nile virus- and dengue virus
      infected patients. In combination with indirect immunofluorescence, to exclude
      four false-positive samples, the specificity was 100% (280 samples). Assuming a
      prevalence rate of anti-West-Nile virus antibodies of 5%, the positive and
      negative predictive values were 93.3% and 98.8% respectively. These results
      indicate that the reverse ELISA using a specific portion of the envelope antigen
      of West Nile virus is especially suitable for studies on the prevalence of West
      Nile infections in affected countries.

PMID- 17554573
TI  - Charcot spine.
AB  - Identification of a destructive spinal process in the acute setting most commonly
      is related to infection or neoplasm. In the appropriate clinical setting, Charcot
      spine, also known as neuropathic spinal arthropathy or spinal neuroarthropathy,
      should be considered. We present a case of spinal destruction due to spinal
      neuroarthropathy in a 51-year-old man who had been paraplegic for 13 years, and
      review the characteristic and potentially differentiating imaging findings of
      this uncommon process.

PMID- 17554574
TI  - Fine mapping of the region on wheat chromosome 7D controlling grain weight.
AB  - We report the fine mapping of the previously described quantitative trait loci
      (QTL) for grain weight QTgw.ipk-7D associated with microsatellite marker Xgwm1002
      7D by using introgression lines (ILs) carrying introgressions of the synthetic
      wheat W-7984 in the genetic background of the German winter wheat variety
      'Prinz'. The BC(4)F(3) ILs had a 10% increased thousand grain weight compared to
      the control group and the recurrent parent 'Prinz', and 84.7% of the phenotypic
      variance could be explained by the segregation of marker Xgwm1002-7D, suggesting
      the presence of a gene modulating grain weight, which was preliminarily
      designated gw1. It was possible to delimit the QTL QTgw.ipk-7D to the interval
      Xgwm295-Xgwm1002, which is located in the most telomeric bin 7DS4-0.61-1.00 in
      the physical map of wheat chromosome arm 7DS. Furthermore, our data suggest the
      presence of a novel plant height-reducing locus Rht on chromosome arm 7DS of
      'Prinz'. Larger grain and increased plant height may reflect the pleiotropic
      action of one gene or may be caused by two linked genes. In general, our data
      support the concept of using nearly isogenic ILs for validating and dissecting
      QTLs into single Mendelian genes and open the gateway for map-based cloning of a
      grain-weight QTL in wheat.

PMID- 17554575
TI  - A cold-active esterase of Streptomyces coelicolor A3(2): from genome sequence to
      enzyme activity.
AB  - The genome sequence of Streptomyces coelicolor A3(2) contains 51 putative lipase
      and esterase genes mostly of unknown function. The gene estB (locus SCO 6966) was
      expressed as a His-tagged protein in E. coli. Esterase B was active at low
      temperatures exerting its maximum activity at 30 degrees C and retaining more
      than 25% of its activity at 4 degrees C. The optimum pH was 8-8.5. The enzyme was
      active against short synthetic p-nitrophenylesters (C2-C10) with maximum activity
      towards the acetate ester (C2). The esterase was tested on 13 series of racemic
      esters of potential interest for the synthesis of chiral pharmaceutical
      compounds. 4 of the series were substrates and a modest degree of
      enantioselectivity was observed (enantiomeric ratios of 1.1-1.9).

PMID- 17554576
TI  - Generation of ENU-induced mouse mutants with hypocholesterolemia: novel tools for
      dissecting plasma lipoprotein homeostasis.
AB  - Pathologic plasma lipoprotein cholesterol levels play a key role in the
      development and pathogenesis of human atherosclerotic cardiovascular diseases.
      Plasma cholesterol homeostasis is regulated by genetic predispositions and
      environmental factors. Animal models showing aberrant plasma cholesterol levels
      are used for the identification and analysis of novel causative genes. Here, we
      searched for inherited hypocholesterolemia phenotypes in randomly mutant mice
      which may contribute to the detection of disease protective alleles. In the
      Munich ENU mouse mutagenesis project, clinical chemistry blood analysis was
      carried out on more than 15,500 G1 offspring and 230 G3 pedigrees of chemically
      mutagenized inbred C3H mice to detect dominant and recessive mutations leading to
      a decreased plasma total cholesterol level. We identified 66 animals consistently
      showing hypocholesterolemia. Transmission of the altered phenotype to the
      subsequent generations led to the successful establishment of 14 independent
      hypocholesterolemic lines. Line-specific differences were detected by clinical
      chemistry analysis of plasma HDL cholesterol, LDL cholesterol and triglycerides.
      Thus, we successfully established a novel panel of ENU-derived mutant mouse lines
      for their use in the identification of alleles selectively influencing the plasma
      cholesterol homeostasis. Such findings may be subsequently used for humans and
      other species.

PMID- 17554577
TI  - Task-dependent organization of pinch grip forces.
AB  - The organization of thumb and index finger forces in a pinch formation was
      investigated under conditions where kinetic constraints on interdigit force
      coupling were removed. Two visually guided isometric force tasks at submaximal
      levels were used to characterize the spatial and temporal aspects of interdigit
      force coupling. Task 1 provided an initial characterization of interdigit force
      coordination when the force relationship between the digits was not specified.
      Task 2 probed the extent to which a preferred coordination of the thumb and index
      finger could be decoupled, both temporally and with respect to force magnitude,
      by specifying the coordination between the digit forces. Digit forces were
      measured using a pinch apparatus that was instrumented to record the magnitude
      and direction of the thumb (F(t)) and index finger (F(i)) forces, independently.
      Two apparatus conditions allowed further examination of interdigit force
      coordination when the relationship between digit forces was mechanically
      constrained (pivot condition), and when the relationship between digit forces was
      not constrained, allowing the neuromotor system to select a preferred pattern of
      interdigit coordination (fixed condition). Sixteen right-handed adults exerted a
      pinch force against the apparatus to match a single-cycle sine wave that varied
      between 15 and 35% of each participant's maximal voluntary pinch force. The
      target was presented with positive or negative target sense, to vary the order of
      force level and direction of force change across the trials. When the mechanical
      constraints allowed selection of a preferred coordination pattern, F(t) = F(i)
      was a robust result. In contrast, when the coordination between the digit forces
      was specified by the requirement to simultaneously produce and control
      independent thumb and index finger forces while acting on a stable object,
      subjects were able to produce forces that markedly deviated from the F(t) = F(i)
      coordination. The organization of pinch is characterized by a preferred, tight
      coupling of digit forces, which can be modified based on task demands.

PMID- 17554578
TI  - Thrombophlebitis migrans as a footprint of Buerger's disease: a prospective
      descriptive study in north-east of Iran.
AB  - The pathogenesis of thrombophlebitis migrans is as unknown as the etiology of
      Buerger's disease (BD). In the past, thrombophlebitis migrans was a major
      criterion used in the diagnosis of BD, whereas today it is not as important as
      before and it is often forgotten to be asked about from patients with BD. In this
      project, during a 22-month prospective study on 86 patients suffering from BD,
      65.4% had the history or sign of thrombophlebitis migrans, which in 25.6% of
      them, it was the first presentation of the disease and in 4.7% of them, it was
      the main cause of complaint. Thrombophlebitis migrans had initially occurred 9
      years before the patient showed any sign of the disease (with the time range of a
      maximum of 22 years and a minimum of 4 months). In 45% of patients who had
      recommenced cigarette smoking, thrombophlebitis migrans occurred about 1-4 months
      before the new onset of their acute ischemic signs. Superficial thrombophlebitis
      migrans can be considered as a warning sign for BD onset in Asian young male
      smokers. With regard to the variety in the clinical feature and localization of
      appearance of thrombophlebitis migrans in the studied patients and its unknown
      pathogenesis, there should be more studies and researches toward understanding
      the nature of BD and thrombophlebitis migrans as its footprint.

PMID- 17554579
TI  - Risk-based evaluation of thromboprophylaxis among surgical inpatients: are low
      risk patients treated unnecessarily?
AB  - BACKGROUND: Venous thromboembolism is a common source of morbidity and mortality
      but a variety of preventative measures are available. AIMS: To audit the current
      practice of thromboprophylaxis and compare against published protocols. METHODS:
      Three-hundred and seventy-six (376) surgical patients were surveyed
      prospectively. A Performa was completed recording the presence of up to 11 risk
      factors. A risk score was calculated and the use of specific thromboprophylatic
      measures identified. RESULTS: Heparin thromboprophylaxis was widely used, eight
      patients (who were on aspirin therapy) failed to receive any prophylaxis (risk
      factors 4-6). In addition there were 60 patients at low risk (risk score <2)
      received LMWH from which they were unlikely to benefit. CONCLUSIONS:
      Thromboembolic prophylaxis is widely but unselectively applied. Adoption of a
      risk: benefit ratio approach should ensure those who would benefit from
      thromboprophylaxis are adequately treated while those in whom thromboprophylaxis
      is not indicated are spared unnecessary therapy.

PMID- 17554580
TI  - Comparison of dried plum supplementation and intermittent PTH in restoring bone
      in osteopenic orchidectomized rats.
AB  - Bone loss was confirmed after 90 days in 50 6-month-old male Sprague Dawley rats
      that were sham-operated or orchidectomized (ORX). In this study, we have shown
      that dried plum (DP) has potent effects on bone in terms of bone mass,
      microarchitecture, and strength in osteopenic male rats. Although these changes
      may be mediated through the suppression of bone resorption, the fact that the
      restoration in some of the bone structural and biomechanical parameter shares
      some similarities with parathyroid hormone (PTH) should not be overlooked.
      Further investigation is needed on a mechanistic level to clarify the influence
      of DP on bone metabolism. INTRODUCTION: This study was designed to investigate
      the extent to which DP reverses bone loss in osteopenic ORX rats and to compare
      its effects to PTH. MATERIALS AND METHODS: Fifty, 6-month-old male Sprague Dawley
      rats were sham-operated or ORX, and bone loss was confirmed after 90 days. The
      ORX groups were assigned to control (AIN-93M) diet, 25% DP diet, or PTH (80
      microg/kg) for 90 days. RESULTS: DP induced an 11% increase in vertebral and
      femoral BMD compared to ORX-controls. BMD in the PTH-treated group was increased
      by 20.7% (vertebra) and 17.9% (femur). Vertebral trabecular bone volume (BV/TV)
      and number were increased by DP and trabecular separation was decreased compared
      to controls, which were similar to PTH. Alterations in trabecular bone of the
      femur were similar to those in the vertebra, but DP did not restore BV/TV to the
      same extent. Cortical thickness was improved by DP and further enhanced by PTH.
      DP tended to decrease urinary deoxypyridinoline and calcium, but did not alter
      alkaline phosphatase or osteocalcin. CONCLUSION: We conclude that though the
      degree of improvement was not equivalent to PTH with regard to all parameters, DP
      reverses bone loss due to ORX and the mechanisms should be further investigated.

PMID- 17554581
TI  - Risedronate reduces postoperative bone resorption after cementless total hip
      arthroplasty.
AB  - Forty-three patients who had undergone cementless THA were randomly assigned to
      receive no osteoactive drug or oral risedronate for 6 months. Postoperative
      decrease of BMD in the risedronate group was significantly lower than that seen
      in the control group in zones 1, 2, 3, 6, and 7. INTRODUCTION: Proximal bone
      resorption around the femoral stem often has been observed after total hip
      arthroplasty (THA), could lead to late stem loosening. We previously reported the
      efficacy of etidronate on periprosthetic bone resorption after cementless THA.
      Recently risedronate is suggested to be effective for the prevention and
      treatment of for osteoporosis. The purpose of the present study was to evaluate
      the effects of risedronate on periprosthetic bone loss after cementless THA.
      METHODS: Forty-three patients who had undergone cementless THA were randomly
      assigned to receive no osteoactive drug (21 patients) or oral risedronate 2.5
      mg/day (22 patients) for 6 months. Three patients were eliminated from the
      risedronate group because of dyspepsia. Periprosthetic bone mineral density (BMD)
      in seven regions of interest based on the zones of Gruen et al. was measured with
      dual energy X-ray absorptiometry at 3 weeks and 6 months postoperatively.
      RESULTS: At 6 months after surgery, postoperative decrease of BMD in the
      risedronate group was significantly lower than that seen in the control group in
      zones 1, 2, 3, 6, and 7 (p < 0.05, p < 0.01, p < 0.01, p < 0.05, and p < 0.05,
      respectively). CONCLUSION: These outcomes suggested that risedronate might reduce
      the periprosthetic bone resorption after cementless THA.

PMID- 17554582
TI  - Voice recognition dictation: radiologist as transcriptionist.
AB  - Continuous voice recognition dictation systems for radiology reporting provide a
      viable alternative to conventional transcription services with the promise of
      shorter report turnaround times and increased cost savings. While these benefits
      may be realized in academic institutions, it is unclear how voice recognition
      dictation impacts the private practice radiologist who is now faced with the
      additional task of transcription. In this article, we compare conventional
      transcription services with a commercially available voice recognition system
      with the following results: 1) Reports dictated with voice recognition took 50%
      longer to dictate despite being 24% shorter than those conventionally
      transcribed, 2) There were 5.1 errors per case, and 90% of all voice recognition
      dictations contained errors prior to report signoff while 10% of transcribed
      reports contained errors. 3). After signoff, 35% of VR reports still had errors.
      Additionally, cost savings using voice recognition systems in non-academic
      settings may not be realized. Based on average radiologist and transcription
      salaries, the additional time spent dictating with voice recognition costs an
      additional $6.10 per case or $76,250.00 yearly. The opportunity costs may be
      higher. Informally surveyed, all radiologists expressed dissatisfaction with
      voice recognition with feelings of frustration, and increased fatigue. In
      summary, in non-academic settings, utilizing radiologists as transcriptionists
      results in more error ridden radiology reports and increased costs compared with
      conventional transcription services.

PMID- 17554583
TI  - Cell proliferation and oxygen diffusion in a vascularising scaffold.
AB  - The supply of oxygen to proliferating cells within a scaffold is a key factor for
      the successful building of new tissue in soft tissue engineering applications. A
      recent in vivo model, where an arteriovenous loop is placed in a scaffold, allows
      a vascularising network to form within a scaffold, establishing an oxygen source
      within, rather than external, to the scaffold. A one-dimensional model of oxygen
      concentration, cell proliferation and cell migration inside such a vascularising
      scaffold is developed and investigated. In addition, a vascularisation model is
      presented, which supports a vascularisation front which moves at a constant
      speed. The effects of vascular growth, homogenous and heterogenous seeding,
      diffusion of cells and critical hypoxic oxygen concentration are considered. For
      homogenous seeding, a relationship between the speed of the vascular front and a
      parameter defining the rate of oxygen diffusion relative to the rate of oxygen
      consumption determines whether a hypoxic region exists at some time. In
      particular, an estimate of the length of time that a fixed point in the scaffold
      will remain under hypoxic conditions is determined. For heterogenous seeding, a
      Fisher-like travelling wave of cells is established behind the vascular front.
      These findings provide a fundamental understanding of the important interplay
      between the parameters and allows for a theoretical assessment of a seeding
      strategy in a vascularising scaffold.

PMID- 17554584
TI  - Kinetics of aggregate formation in social insects.
AB  - A model for the kinetics of aggregation in social insects which accounts for
      stochastic effects arising from individual variability and covers both the early
      and the mature stages of the process is developed. Different aggregation
      scenarios are studied, depending on the degree of cooperativity and the mean
      population density. It is shown that under certain conditions, the system evolves
      slowly to a single cluster incorporating all individuals, or to two coexisting
      clusters of similar sizes.

PMID- 17554585
TI  - Modeling within-host evolution of HIV: mutation, competition and strain
      replacement.
AB  - Virus evolution during infection of a single individual is a well-known feature
      of disease progression in chronic viral diseases. However, the simplest models of
      virus competition for host resources show the existence of a single dominant
      strain that grows most rapidly during the initial period of infection and
      competitively excludes all other virus strains. Here, we examine the dynamics of
      strain replacement in a simple model that includes a convex trade-off between
      rapid virus reproduction and long-term host cell survival. Strains are structured
      according to their within-cell replication rate. Over the course of infection, we
      find a progression in the dominant strain from fast- to moderately-replicating
      virus strains featuring distinct jumps in the replication rate of the dominant
      strain over time. We completely analyze the model and provide estimates for the
      replication rate of the initial dominant strain and its successors. Our model
      lays the groundwork for more detailed models of HIV selection and mutation. We
      outline future directions and application of related models to other biological
      situations.

PMID- 17554587
TI  - Examining emergence of functional gene clustering in a simulated evolution.
AB  - Recent research suggests that rather than being random, gene order may be coupled
      with gene functionality. These findings may be explained by mechanisms that
      require physical proximity such as co-expression and co-regulation.
      Alternatively, they may be due to evolutionary-dynamics forces, as expressed in
      genetic drift or linkage disequilibrium. This paper proposes a biologically
      plausible model for evolutionary development. Using the model, which includes
      natural selection and the development of gene networks and cellular organisms,
      the co-evolution of recombination rate and gene functionality is examined. The
      results presented here are compatible with previous biological findings showing
      that functionally related genes are clustered. These results imply that
      evolutionary pressure in a complex environment is sufficient for the emergence of
      gene order that is coupled with functionality. They shed further light on the
      mechanisms that may cause such gene clusters.

PMID- 17554586
TI  - G-CSF control of neutrophils dynamics in the blood.
AB  - White blood cell neutrophil is a key component in the fast initial immune
      response against bacterial and fungal infections. Granulocyte colony stimulating
      factor (G-CSF) which is naturally produced in the body, is known to control the
      neutrophils production in the bone marrow and the neutrophils delivery into the
      blood. In oncological practice, G-CSF injections are widely used to treat
      neutropenia (dangerously low levels of neutrophils in the blood) and to prevent
      the infectious complications that often follow chemotherapy. However, the
      accurate dynamics of G-CSF neutrophil interaction has not been fully determined
      and no general scheme exists for an optimal G-CSF application in neutropenia.
      Here we develop a two-dimensional ordinary differential equation model for the G
      CSF-neutrophil dynamics in the blood. The model is built axiomatically by first
      formally defining from the biology the expected properties of the model, and then
      deducing the dynamic behavior of the resulting system. The resulting model is
      structurally stable, and its dynamical features are independent of the precise
      form of the various rate functions. Choosing a specific form for these functions,
      three complementary parameter estimation procedures for one clinical (training)
      data set are utilized. The fully parameterized model (6 parameters) provides
      adequate predictions for several additional clinical data sets on time scales of
      several days. We briefly discuss the utility of this relatively simple and robust
      model in several clinical conditions.

PMID- 17554588
TI  - Antagonistic and synergistic interactions among predators.
AB  - The structure and dynamics of food webs are largely dependent upon interactions
      among consumers and their resources. However, interspecific interactions such as
      intraguild predation and interference competition can also play a significant
      role in the stability of communities. The role of antagonistic/synergistic
      interactions among predators has been largely ignored in food web theory. These
      mechanisms influence predation rates, which is one of the key factors regulating
      food web structure and dynamics, thus ignoring them can potentially limit
      understanding of food webs. Using nonlinear models, it is shown that critical
      aspects of multiple predator food web dynamics are antagonistic/synergistic
      interactions among predators. The influence of antagonistic/synergistic
      interactions on coexistence of predators depended largely upon the parameter set
      used and the degree of feeding niche differentiation. In all cases when there was
      no effect of antagonism or synergism (a ( ij )=1.00), the predators coexisted.
      Using the stable parameter set, coexistence occurred across the range of
      antagonism/synergism used. However, using the chaotic parameter strong antagonism
      resulted in the extinction of one or both species, while strong synergism tended
      to coexistence. Whereas using the limit cycle parameter set, coexistence was
      strongly dependent on the degree of feeding niche overlap. Additionally
      increasing the degree of feeding specialization of the predators on the two prey
      species increased the amount of parameter space in which coexistence of the two
      predators occurred. Bifurcation analyses supported the general pattern of
      increased stability when the predator interaction was synergistic and decreased
      stability when it was antagonistic. Thus, synergistic interactions should be more
      common than antagonistic interactions in ecological systems.

PMID- 17554589
TI  - Prostate cancer testing following a negative prostate biopsy: over testing the
      elderly.
AB  - BACKGROUND: Screening elderly men for prostate cancer is not recommended because
      definitive treatments are unlikely to extend life expectancy. OBJECTIVE: Describe
      clinical outcomes after a negative prostate biopsy in a population-based cohort
      of men ages 65 and older. DESIGN: Retrospective cohort study. PARTICIPANTS: 9,410
      Medicare-eligible men who underwent a prostate biopsy in Los Angeles or New
      Mexico in 1992. MEASUREMENTS: We used Medicare and SEER databases to identify a
      cohort with an initial negative biopsy (n = 7,119) and to ascertain survival,
      subsequent PSA testing, prostate biopsies, and prostate cancer detection and
      treatment through 1997. RESULTS: The overall 5-year survival was 79.4% (95% CI
      78.4-80.3), but only 74.6% (72.4-76.7) for men ages 75-79 at the time of the
      initial negative biopsy and 55.0% (51.9-57.9) for men ages 80+. During a median
      4.5 years follow-up, a cumulative 75.0% (73.9-76.1) of the cohort underwent PSA
      testing. Among men ages 75-79 and 80+, the cumulative proportions that underwent
      PSA testing were 75.4% (73.0-77.8) and 74.3% (71.1-77.5), respectively.
      Additionally, 29.1% (26.7-31.6) of men ages 75-79 and 20.1% (17.6-23.1) of men
      ages 80+ underwent repeat prostate biopsy, and 10.9% (9.4-12.7) and 8.3% (6.6
      10.4), respectively, were diagnosed with cancer. Among men ages 75+ with
      localized cancers, approximately 34% received definitive treatment. CONCLUSIONS:
      High proportions of men ages 75+ underwent PSA testing and repeat prostate
      biopsies after an initial negative prostate biopsy. Given the known harms and
      uncertain benefits for finding and treating localized cancer in elderly men, most
      continued PSA testing after a negative biopsy is potentially inappropriate.

PMID- 17554590
TI  - Isolation and characterization of two novel colon cancer cell lines from Chinese
      patients.
AB  - Incidence of colon cancer has increased rapidly in China. Although many colon
      cancer cell lines have been established previously, most of them were derived
      from patients from western countries. Epidemiological, clinical, cytogenetic, and
      molecular biological studies showed that there are considerable differences
      between Chinese and western countries colon cancer patients. Therefore,
      establishment of novel colon cancer cell line from Chinese is useful for studying
      the racial difference of this disease and can be important for studying the
      pathogenesis of colon cancer in China. In our laboratory, two novel continuous
      human colon cancer cell lines, SHT-1 and SHH-1, have been established in vitro
      from Chinese patients, and both cell lines have been passaged for 4 yr, and they
      have been continuously subcultured with more than 800 population doubling and
      without signs of senescence. Both cell lines were obtained from primary tumor
      tissues during colon cancer surgery. Cells grew rapidly with a doubling time of
      36-39 h and a plating efficiency of 26-28%. These cells exhibited an epithelial
      morphology and expressed cytokeratin. Tumor developed in severe combined
      immunodeficient (SCID) mice 4-6 wk after inoculated subcutaneously with the
      cultured cancer cells. Karyotypic analysis and comparative genomic hybridization
      (CGH) analysis in SHT-1 cells revealed a hypertriploid modal number of 76 with
      numerous numerical and structural abnormalities previously linked to colon
      cancer. In another cell line (SHH-1), CGH analysis revealed that -1p13 was the
      only cytogenetic anomaly.

PMID- 17554591
TI  - Effect of storage conditions on detection of mycoplasma in biopharmaceutical
      products.
AB  - Mycoplasma contamination affects many different aspects of cell culturing,
      resulting in unreliable experimental results and potentially harmful biological
      products. Therefore, the specificity, sensitivity, and reliability of detecting
      mycoplasma contamination are important aspects of quality control in
      biotechnological products. In this study, Mycoplasma hyorhinis was adopted as a
      model strain to evaluate the effects of storage on the viability of Mycoplasma
      species in cell culture samples. Medium X was compared with conventional media
      243 and 988 for the ability to detect M. hyorhinis. The 10(1) CFU/ml of M.
      hyorhinis was inoculated into medium X prepared using the same lots of components
      and preserved for 7 d, 1 mo, and 2 mo. M. hyorhinis grew readily and typically on
      agar plates prepared within 1 mo. The viable mycoplasmas in samples containing
      different initial titers (10(1) and 10(6) CFU/ml) after storage at 4 degrees C
      and -30 degrees C were analyzed. During storage, viable organisms were found with
      little or no reduction in titers after storage for 8 wk at -30 degrees C under
      aerobic and anaerobic conditions. A reduction in titers of 3 log10 occurred after
      4 wk storage for high-dose cultures (10(6) CFU/ml) at 4 degrees C. The titers of
      viable organisms were diminished over 8 wk at 4 degrees C under aerobic and
      anaerobic conditions.

PMID- 17554592
TI  - UXT (Ubiquitously Expressed Transcript) causes mitochondrial aggregation.
AB  - Mitochondria are the bioenergetic and metabolic centers in eukaryotic cells and
      play a central role in apoptosis. Mitochondrial distribution is controlled by the
      microtubular cytoskeleton. The perinuclear aggregation of mitochondria is one of
      the characteristics associated with some types of cell death. Control of
      mitochondrial aggregation particularly related to cell death events is poorly
      understood. Previously, we identified ubiquitously expressed transcript (UXT) as
      a potential component of mitochondrial associated LRPPRC, a multidomain organizer
      that potentially integrates mitochondria and the microtubular cytoskeleton with
      chromosome remodeling. Here we show that when overexpressed in mammalian cells,
      green fluorescent protein-tagged UXT (GFP-UXT) exhibits four types of
      distribution patterns that are proportional to the protein level, and increase
      with time. UXT initially was dispersed in the extranuclear cytosol, then appeared
      in punctate cytosolic dots, then an intense perinuclear aggregation that
      eventually invaded and disrupted the nucleus. The punctate cytosolic aggregates
      of GFP-UXT coincided with aggregates of mitochondria and LRPPRC. We conclude that
      increasing concentrations of UXT contributes to progressive aggregation of
      mitochondria and cell death potentially through association of UXT with LRPPRC.

PMID- 17554593
TI  - Vascular endothelial growth factors in pulmonary edema: an update.
AB  - Pulmonary edema is a life-threatening complication of critical illness.
      Identification of the underlying mechanisms of pulmonary edema is a prerequisite
      for the development of adequate treatment. The initial description of fluid
      transportation across capillaries (Starling's law) while of critical importance,
      did not provide full insight into the underlying pathophysiology of vascular
      leakage. Pulmonary edema can be differentiated into two distinct categories based
      on the Starling theory; the high-permeability type is attributed to inflammatory
      changes occurring in conditions such as the adult respiratory distress syndrome
      (ARDS) and the cardiogenic type is characterized by an imbalance in the Starling
      hydrostatic forces and occurs in acute or decompensated heart failure. However,
      it has long been recognized that there is significant overlap between the various
      types of pulmonary edema, raising important questions regarding the role of novel
      mechanisms that may contribute to the development of interstitial and alveolar
      leakage. Recently, several studies on VEGF, an angiogenic growth factor which
      affects endothelial permeability, have identified this molecule as a potential
      regulator of vascular leakage and repair in pulmonary edema. We review here the
      underlying the mechanisms by which VEGF may do this and will discuss the still
      unanswered questions regarding vascular pharmacology in the setting of pulmonary
      edema.

PMID- 17554594
TI  - Abnormal PFA-100 closure time is associated with increased platelet aggregation
      in patients presenting with chest pain.
AB  - BACKGROUND: Antiplatelet therapy has been proven to be effective for both primary
      and secondary prevention of myocardial infarction, stroke, and cardiovascular
      death. However, a significant proportion of patients treated with aspirin
      experience ischemic events. A number of prospective studies have demonstrated
      that decreased responsiveness to antiplatelet therapy as measured by various
      methods, is strongly associated with an increase in clinical events. Our
      objective was to characterize platelet function in patients presenting with chest
      pain using a point-of-care assay, PFA-100 and correlating results to traditional
      platelet aggregometry to determine if patients with aspirin non-responsiveness
      have increased clinical sequelae. METHODS: Platelet function was assessed using
      PFA-100, flow cytometry, and optical aggregometry in 94 patients presenting to
      the emergency department with chest pain. All patients were on aspirin 81-325 mg
      daily. Clinical events occurring during the index hospitalization were
      documented. RESULTS: Forty-seven patients (50%) were defined as aspirin non
      responders by PFA-100 (collagen-epinephrine closure time <or= 193). Compared to
      aspirin responders, aspirin non-responders had higher levels of mean platelet
      aggregation to adenosine diphosphate (ADP) (P = 0.004) and high dose epinephrine
      (P = 0.03). Furthermore, expression of PAC-1 was significantly increased in
      patients with aspirin nonresponse as compared to aspirin responders (P = 0.003
      and P = 0.0006 respectively). No significant difference in clinical events during
      the index hospitalization was noted between aspirin non-responders and aspirin
      responders. CONCLUSION: Patients presenting with chest pain who have abnormal PFA
      100 closure times have increased platelet aggregation and activation however this
      aspirin non-responsiveness does not correlate with increased clinical events in
      the index hospitalization.

PMID- 17554595
TI  - Preparation of hydroxyapatite/poly(methyl methacrylate) and calcium
      silicate/poly(methyl methacrylate) interpenetrating hybrid composites.
AB  - Hydroxyapatite/poly(methyl methacrylate) (HAp/PMMA) and calcium
      silicate/poly(methyl methacrylate) (CS/PMMA) composites were prepared by
      interpenetrating bulk polymerization of methyl methacrylate (MMA) monomer in
      porous structures of HAp and CS. The porous HAp and CS templates were prepared by
      mixing their calcined powders with poly(vinyl alcohol) (PVA) solution, shaping by
      uniaxial pressing and then firing at 1,100 degrees C for HAp and 900 degrees C
      for CS. The templates were soaked in the solution mixture of MMA monomer and 0.1
      mol% of benzoyl peroxide (BPO) for 24 h. The pre-composites were then bulk
      polymerized at 85 degrees C for 24 h under nitrogen atmosphere. The
      microstructures of the composites showed the interpenetrating of PMMA into the
      porous HAp and CS structures. Thermogravimetric analysis indicated that the PMMA
      content in the HAp/PMMA and CS/PMMA composites were 13 and 26 wt%, respectively.
      Weight average molecular weights (M(w)) of PMMA were about 491,000 for HAp/PMMA
      composites and about 348,000 for CS/PMMA composites. Compressive strengths of
      these composites were about 90-131 MPa in which they were significantly higher
      than their starting porous templates.

PMID- 17554596
TI  - Fabrication and mechanical testing of porous calcium phosphate bioceramic
      granules.
AB  - Porous hydroxyapatite/tricalcium phosphate (HA/TCP) granules were fabricated by a
      novel technique of vacuum impregnation of reticulated polyurethane (PU) foams
      with ceramic slip. The resultant granules had 5-10% interconnected porosity with
      controlled pore sizes necessary to allow bone ingrowth combined with good
      mechanical properties. Using PU foams with a different number of pores per inch
      (ppi), porous HA/TCP granules in the size range of 2-8 mm were successfully
      manufactured. Dieplunger tests were used to compare the compression and
      relaxation properties of the granules with those of a commercially available bone
      graft product, BoneSave. The results of the die-plunger testing showed that the
      experimental granules were stiffer than the BoneSave materials and had less of a
      tendency to crumble to powder after testing. This therefore suggests that these
      experimental granules would be useful for impaction grafting and space filling
      applications.

PMID- 17554598
TI  - Functionalization of different polymers with sulfonic groups as a way to coat
      them with a biomimetic apatite layer.
AB  - Covalent coupling of sulfonic group (-SO 3H) was attempted on different polymers
      to evaluate efficacy of this functional group in inducing nucleation of apatite
      in body environment, and thereupon to design a simple biomimetic process for
      preparing bonelike apatite-polymer composites. Substrates of polyethylene
      terephthalate (PET), polycaprolactam (Nylon 6), high molecular weight
      polyethylene (HMWPE) and ethylene-vinyl alcohol co-polymer (EVOH) were subjected
      to sulfonation by being soaked in sulfuric acid (H2SO4) or chlorosulfonic acid
      (ClSO 3H) with different concentrations. In order to incorporate calcium ions,
      the sulfonated substrates were soaked in saturated solution of calcium hydroxide
      (Ca(OH)2). The treated substrates were soaked in a simulated body fluid (SBF).
      Fourier transformed infrared spectroscopy, thin-film X-ray diffraction, and
      scanning electron microscopy showed that the sulfonation and subsequent Ca(OH)2
      treatments allowed formation of -SO3H groups binding Ca2+ ions on the surface of
      HMWPE and EVOH, but not on PET and Nylon 6. The HMWPE and EVOH could thus form
      bonelike apatite layer on their surfaces in SBF within 7 d. These results
      indicate that the -SO3H groups are effective for inducing apatite nucleation, and
      thereby that surface sulfonation of polymers are effective pre-treatment method
      for preparing biomimetic apatite on their surfaces.

PMID- 17554597
TI  - The effect of physiological cyclic stretch on the cell morphology, cell
      orientation and protein expression of endothelial cells.
AB  - In vivo, endothelial cells are constantly exposed to pulsatile shear and tensile
      stresses. The main aim of this study was to design and build a physiological
      simulator, which reproduced homogenous strain profiles of the tensile strain
      experienced in vivo, and to investigate the effect of this cyclic tensile strain
      on the cell morphology, cell orientation and protein expression of endothelial
      cells. The biological response of human umbilical vein endothelial cells to a
      uniaxial cyclic stretch, in this newly developed simulator, was examined
      experimentally using immunohistostaining and confocal imaging and it was found
      that the cells elongated and oriented at 58.9 degrees +/- 4.5 degrees . This
      value was compared to a mathematical model where it was revealed that endothelial
      cells would orient at an angle of 60 degrees . This model also revealed that
      endothelial cells have an axial strain threshold value of 1.8% when exposed to a
      10% cyclic strain at 1 Hz for 3 h. Cells cultured under conditions of cyclic
      strain showed increased ICAM-1 immunostaining when compared to static cells
      whereas, a marked decrease in the levels of VCAM-1 receptor staining was also
      observed. Haemodynamic stresses can modulate the endothelial cell adhesion
      response in vivo thus, taken together; this data validates the bioreactor as
      replicating the physiological environment.

PMID- 17554599
TI  - On the growth model of the capillaries in the porous silk fibroin films.
AB  - This paper discussed the random growth model of the capillaries in its growing
      process, analyzed the relations between the growth of the capillaries, the
      metabolism of the organism tissue, and micro environmental condition and
      secretion of the growth factors. Furthermore, the paper discussed the growth law
      of the capillaries in the porous silk fibroin films (PSFF) in order to provide a
      theoretical basis for the designing and making of the new biomaterial of the PSFF
      more suitable for the growth of the cells and capillaries.

PMID- 17554600
TI  - Evaluation of a new composite prosthesis for the repair of abdominal wall
      defects.
AB  - The degree of integration of biomaterials used in the repair of abdominal wall
      defects seems to depend upon the structure of the prosthesis. The present
      investigation evaluates the behaviour in terms of adhesion formation and
      integration of a new composite prosthesis that could be employed in this clinical
      application. Full-thickness abdominal wall defects (7 x 5 cm) were created in 16
      anaesthetized New Zealand white rabbits and the prosthesis were placed in direct
      contact with the visceral peritoneum during the experiment. The defects were
      repaired with a composite prosthesis or pure polypropylene mesh to establish two
      study groups (n = 8 each). The composite device was constituted by a
      polypropylene mesh physically attached to a poly(ether)urethane
      polydimethylsiloxane laminar sheet. Animals were sacrificed 7, 14, 21 and 30 days
      after implant and prosthesis/surrounding tissue specimens subjected to light and
      electron microscopy. Firm adhesions were detected in the polypropylene implants,
      while they were not present in the composite implants. The excellent behaviour of
      the composite prosthesis shown in this study warrants further investigation on
      its use for the repair of abdominal wall defects when a prosthetic device needs
      to be placed in contact with the intestinal loops.

PMID- 17554601
TI  - Interactions of total bone marrow cells with increasing quantities of macroporous
      calcium phosphate ceramic granules.
AB  - The biological properties of synthetic calcium phosphate bioceramics have made
      them the third choice of material for bone reconstructive surgery, after
      autologous bone and allografts. Nevertheless, bioceramics lack the osteogenic
      properties that would allow them to repair large bone defects. One strategy in
      bone tissue engineering consists of associating a synthetic scaffold with
      osteogenic cells. Mesenchymal stem cells (MSC) are usually isolated from bone
      marrow cultured for several weeks and seeded on to a small quantity of
      bioceramic. We have studied the association of total bone marrow cells, harvested
      from femurs of rats, with increasing amounts of calcium phosphate ceramic
      granules (50-250 mg). A cell viability test indicated that a little quantity of
      bioceramics granules (50 mg) was less detrimental for culturing 1 million
      nucleated cells from the whole bone marrow population. Cell morphology,
      viability, adhesion and differentiation were studied after different culture
      periods. Among the heterogeneous population of bone marrow cells, only a limited
      amount of cells attached and differentiated on the bioceramics. To explain the
      influence of the amount of synthetic scaffold on cell viability, media calcium
      concentrations were measured. Low cell viability could be explained by calcium
      phosphate precipitation leading to a decrease in calcium concentrations observed
      with relatively large amounts of scaffold. This study showed that the chemical
      stability of the ceramic plays a critical role in the viability of bone marrow
      cells.

PMID- 17554602
TI  - Formation of calcium phosphates on titanium implants with four different
      bioactive surface preparations. An in vitro study.
AB  - The aim of the present study was to compare the nucleating and growing behaviour
      on four types of bioactive surfaces by using the simulated body fluid (SBF)
      model. Titanium discs were blasted and then prepared by alkali and heat
      treatment, anodic oxidation, fluoridation, or hydroxyapatite coating. The discs
      were immersed in SBF for 1, 2, 4 and 6 weeks. Calcium phosphates were found on
      all specimens, as analysed with scanning electron microscopy/energy dispersive X
      ray analysis (SEM/EDX). After 1 and 2 weeks of SBF immersion more titanium was
      accessible with SEM/EDX on the blasted surfaces than the four bioactive surface
      types, indicating a difference in coverage by calcium phosphates. The Ca/P mean
      ratio of the surfaces was approximately 1.5 after 1 week, in contrast to the
      fluoridated specimens which displayed a Ca/P mean ratio of approximately 2.
      Powder X-ray diffraction (P-XRD) analyses showed the presence of hydroxyapatite
      on all types of surfaces after 4 and 6 weeks of immersion. The samples immersed
      for 6 weeks showed a higher degree of crystallinity than the samples immersed for
      4 weeks. In conclusion, differences appeared at the early SBF immersion times of
      1 and 2 weeks between controls and bioactive surface types, as well as between
      different bioactive surface types.

PMID- 17554603
TI  - Gelatin/chitosan/hyaluronan ternary complex scaffold containing basic fibroblast
      growth factor for cartilage tissue engineering.
AB  - Gelatin, chitosan and hyaluronan with a weight ratio of 82.6%, 16.5% and 0.1%
      were chosen as a scaffold material to mimic the composition of natural cartilage
      matrix for cartilage tissue engineering. Water soluble carbodiimide was added
      into the biomacromolecule solution with a concentration of 5% to crosslink the
      complex. Following a freeze-drying procedure, a porous scaffold (control) was
      then prepared. To enhance chondrogenesis, heparin was covalently immobilized onto
      the scaffold by carbodiimide chemistry, through which basic fibroblast growth
      factor (bFGF) was further incorporated by a bioaffinity force. Incubation in
      phosphate buffered saline (PBS, pH 7.4) at 37 degrees C caused the weight loss of
      all kinds of the scaffolds, which could be brought by both the degradation and
      dissolution of the biomacromolecules. Compared with the control, however, the
      heparinized scaffold showed stronger ability to resist the weight loss, implying
      that a higher crosslinking degree was achieved by incorporation of the heparin.
      Rabbit auricular chondrocytes were seeded onto the ternary complex scaffold
      containing bFGF to assess cell response. Chondrocytes could adhere and
      proliferate in all kinds of the scaffold, regardless of the existence of bFGF. No
      significant difference on glycosaminoglycan (GAG) secretion was recorded between
      these scaffolds after cultured for 7 and 21 days too, although the absolute value
      from the Scaffold-heparin-bFGF was somewhat higher. However, chondrocytes seeded
      in the Scaffold-heparin-bFGF indeed showed significant higher viability than that
      on the control scaffold. These results reveal that the ternary complex scaffolds,
      in particular the one containing bFGF, are a potential candidate for cartilage
      tissue engineering.

PMID- 17554604
TI  - Absorbable collagen sponge combined with recombinant human basic fibroblast
      growth factor promotes nerve regeneration in rat sciatic nerve.
AB  - Recombinant human basic fibroblast growth factor (rhbFGF) is a peptide with many
      bioactivities such as promoting proliferation and migration of various cells. It
      plays an important role in neuroprotection and enhancement of nerve regeneration.
      Due to its short half-life in the body, local administration by injection is
      limited. To prolong the bioactivity of rhbFGF and to enhance its biological
      effects, absorbable collagen sponge was used as matrixes and carriers for
      controlled release of rhbFGF. The effects of rhbFGF soaked into an absorbable
      collagen sponge (rhbFGF/ACS) for the repair of rat sciatic nerve injury were
      evaluated. The functional, electrophysiological and histological examinations
      demonstrate the treatment with rhbFGF/ACS can enhance rat sciatic nerve repair,
      and its effectiveness is better than free rhbFGF alone. It is concluded the
      rhbFGF/ACS is a promising biomaterial to improve the repair and regeneration of
      sciatic nerve injury.

PMID- 17554605
TI  - Assessment of cell viability in a three-dimensional enzymatically cross-linked
      collagen scaffold.
AB  - Microbial transglutaminase (mTGase) is an enzyme that introduces a covalent bond
      between peptide bound glutamine and lysine residues. Proteins cross-linked in
      this manner are often more resistant to proteolytic degradation and show
      increased tensile strength. This study evaluates the effects of mTGase mediated
      cross-linking of collagen on the cellular morphology, behaviour and viability of
      murine 3T3 fibroblasts following their seeding into collagen scaffolds.
      Additionally, cell mediated scaffold contraction, porosity and level of cross
      linking of the scaffold has been analysed using image analysis software, scanning
      electron microscopy (SEM), colorimetric assays, and Fourier transform infrared
      spectroscopy (FTIR). We demonstrate that the biocompatibility and cellular
      morphology, when comparing cultures of fibroblasts integrated in mTGase cross
      linked collagen scaffolds with the native collagen counterparts, remained
      unaffected. It has been also elicited that the structural characteristics of
      collagen have been preserved while introducing enzymatically resistant covalent
      bonds.

PMID- 17554606
TI  - Nanoscale characterisation and imaging of partially amorphous materials using
      local thermomechanical analysis and heated tip AFM.
AB  - PURPOSE: The purpose is to investigate the use of thermal nanoprobes in
      thermomechanical and heated tip pulsed force modes as novel means of
      discriminating between amorphous and crystalline material on a sub-micron scale.
      MATERIALS AND METHODS: Indometacin powder was compressed and partially converted
      into amorphous material. Thermal nanoprobes were used to perform localised
      thermomechanical analysis (L-TMA) and heated tip pulsed force mode imaging as a
      function of temperature. RESULTS: L-TMA with submicron lateral spatial resolution
      and sub-100 nm depth penetration was achieved, allowing us to thermomechanically
      discriminate between amorphous and crystalline material at a nanoscale for the
      first time. The amorphous and crystalline regions were imaged as a function of
      temperature using heated tip pulsed force AFM and a resolution of circa 50 nm was
      achieved. We are also able to observe tip-induced recrystallisation of the
      amorphous material. DISCUSSION: The study demonstrates that we are able to
      discriminate and characterise amorphous and crystalline regions at a submicron
      scale of scrutiny. We have demonstrated the utility of two methods, L-TMA and
      heated tip pulsed force mode AFM, that allow us to respectively characterise and
      image adjacent amorphous and crystalline regions at a nanoscale. CONCLUSIONS: The
      study has demonstrated that thermal nanoprobes represent a novel method of
      characterising and imaging partially amorphous materials.

PMID- 17554607
TI  - Drug targeting to the brain.
AB  - The goal of brain drug targeting technology is the delivery of therapeutics
      across the blood-brain barrier (BBB), including the human BBB. This is
      accomplished by re-engineering pharmaceuticals to cross the BBB via specific
      endogenous transporters localized within the brain capillary endothelium. Certain
      endogenous peptides, such as insulin or transferrin, undergo receptor-mediated
      transport (RMT) across the BBB in vivo. In addition, peptidomimetic monoclonal
      antibodies (MAb) may also cross the BBB via RMT on the endogenous transporters.
      The MAb may be used as a molecular Trojan horse to ferry across the BBB large
      molecule pharmaceuticals, including recombinant proteins, antibodies, RNA
      interference drugs, or non-viral gene medicines. Fusion proteins of the molecular
      Trojan horse and either neurotrophins or single chain Fv antibodies have been
      genetically engineered. The fusion proteins retain bi-functional properties, and
      both bind the BBB receptor, to trigger transport into brain, and bind the cognate
      receptor inside brain to induce the pharmacologic effect. Trojan horse liposome
      technology enables the brain targeting of non-viral plasmid DNA. Molecular Trojan
      horses may be formulated with fusion protein technology, avidin-biotin
      technology, or Trojan horse liposomes to target to brain virtually any large
      molecule pharmaceutical.

PMID- 17554608
TI  - Blood-brain barrier transport of non-viral gene and RNAi therapeutics.
AB  - The development of gene- and RNA interference (RNAi)-based therapeutics
      represents a challenge for the drug delivery field. The global brain distribution
      of DNA genes, as well as the targeting of specific regions of the brain, is even
      more complicated because conventional delivery systems, i.e. viruses, have poor
      diffusion in brain when injected in situ and do not cross the blood-brain barrier
      (BBB), which is only permeable to lipophilic molecules of less than 400 Da.
      Recent advances in the "Trojan Horse Liposome" (THL) technology applied to the
      transvascular non-viral gene therapy of brain disorders presents a promising
      solution to the DNA/RNAi delivery obstacle. The THL is comprised of
      immunoliposomes carrying either a gene for protein replacement or small hairpin
      RNA (shRNA) expression plasmids for RNAi effect, respectively. The THL is
      engineered with known lipids containing polyethyleneglycol (PEG), which
      stabilizes its structure in vivo in circulation. The tissue target specificity of
      THL is given by conjugation of approximately 1% of the PEG residues to
      peptidomimetic monoclonal antibodies (MAb) that bind to specific endogenous
      receptors (i.e. insulin and transferrin receptors) located on both the BBB and
      the brain cellular membranes, respectively. These MAbs mediate (a) receptor
      mediated transcytosis of the THL complex through the BBB, (b) endocytosis into
      brain cells and (c) transport to the brain cell nuclear compartment. The present
      review presents an overview of the THL technology and its current application to
      gene therapy and RNAi, including experimental models of Parkinson's disease and
      brain tumors.

PMID- 17554609
TI  - Characterization of tableting using the OSDRC system.
AB  - PURPOSE: We compared the compression properties and characteristics of tablets
      obtained using the OSDRC system (method (OSDRC)) and conventional compression
      methods including multi-layer compression with a pharmaceutical powder. MATERIALS
      AND METHODS: We prepared tablets using four methods of compression. The force
      profiles, ejection force, stress relaxation, pressure transmission ratio, and
      internal intensity of the tablets were measured as compression properties.
      RESULTS: Method (OSDRC) gave the highest value for the crushing strength of the
      tablets. Although the compression properties were similar regardless of the
      method of compression, the internal intensity of tablets compressed by method
      (OSDRC) was significantly larger than that of the tablets produced by the other
      methods. CONCLUSIONS: In terms of crushing strength, the tablets compressed by
      method (OSDRC) were superior of those obtained by the conventional compression
      method. Therefore, it is possible to increase the crushing strength of tablets
      without changing the pharmaceutical formulation.

PMID- 17554610
TI  - Bioequivalence testing by statistical shape analysis.
AB  - Bioequivalence testing has been traditionally centered in summary variables such
      as AUC, C (max) and t (max) which filter out the intrinsic information conveyed
      by discrete sequential concentration-time observations. Comparing entire
      concentration-time profiles between test and reference formulations for
      bioequivalence purposes provides stronger evidence about either their similarity
      or their discrepancy. The Kullback-Leibler information criterion (KLIC) may be
      computed for each concentration-time across all subjects between formulations of
      the same drug, with a standard crossover study design. It has been shown that if
      properly scaled it follow a chi-squared distribution and dependent p-values may
      be computed in order to construct a bioequivalence criterion. Extensive
      simulations and real data were used to compare it with the current standard
      procedures. This statistical shape analysis method may provide important clinical
      and regulatory advantages.

PMID- 17554611
TI  - I must tell you in a poem: poetry and commentary.

PMID- 17554612
TI  - The effects of prenatal use of folic acid and other dietary supplements on early
      child development.
AB  - OBJECTIVE: Our objective was to evaluate in an exploratory framework the effects
      of prenatal use of folic acid and other dietary supplements on child development
      at around 3 years of life. METHODS: Data from the 1988 National Maternal Infant
      Health Survey and the 1991 follow-up supplement is used. Performance indicators
      are formed based on 16 developmental assessment items completed by the mother to
      measure overall as well as domain specific (language, personal-social, gross
      motor and fine-motor) development. Pooled as well as separate analyses by child
      race are performed. Multinomial and binary outcome logistic regression is used
      and several maternal and household characteristics are included as covariates.
      RESULTS: Folic acid use was associated with improved gross-motor development with
      a more pronounced effect among African-American children, but there was
      marginally significant poorer performance for the personal-social domain. Zinc
      and calcium use were associated with increased risks on the overall development
      scale and two other developmental domains. The negative effects of Zinc on
      overall development were only observed among white children. On the contrary,
      vitamin A was associated with decreased risks on the overall development scale
      only among white children. CONCLUSIONS: Study results suggest that while prenatal
      folic acid supplementation may improve development at 3 years of age, further
      research is needed in this regard. The results also emphasize the importance of
      further research into the use of prenatal calcium and zinc supplementation in a
      US population.

PMID- 17554613
TI  - Impact of pediatricians' perceived self-efficacy and confidence on violence
      prevention counseling: a national study.
AB  - OBJECTIVE: To measure impact of pediatricians' perceived self-efficacy and
      confidence on current practices and attitudes regarding four violence prevention
      (VP) topics (gun storage, gun removal, limiting exposure to media violence,
      discipline techniques) during health supervision for children ages 2-11. METHODS:
      Random sample survey of American Academy of Pediatrics Fellows (n = 486; 53%
      response rate) providing health supervision for children ages 2-11. Participants
      surveyed about VP issues regarding: (1) current counseling practices for 2-5 and
      6-11 year olds; (2) amount of time spent addressing; (3) confidence in
      addressing; and (4) perceived self-efficacy at changing patients' behaviors.
      Multivariate analyses explored relationships between pediatricians' perceived
      self-efficacy and confidence versus VP counseling frequency. RESULTS: VP topics
      were not routinely discussed during health supervision. Most pediatricians (64%)
      reported spending too little time addressing these topics. Although most
      pediatricians felt confident discussing and effective at changing behaviors
      regarding limiting exposure to media violence (89% vs. 50%) and discipline
      techniques (91% vs. 76%), they were less so for safe gun storage (54% vs. 35%)
      and gun removal (51% vs. 17%). Perceived self-efficacy was the mediating factor
      on self-reported VP counseling frequencies for all topics. CONCLUSIONS:
      Pediatricians reported spending insufficient time on VP counseling. Confidence
      and perceived self-efficacy levels varied by VP topic, but for all topics
      pediatricians felt more confident discussing than effective at changing
      behaviors. Since pediatricians' self-efficacy was related to counseling
      practices, boosting self-efficacy could ultimately improve counseling
      frequencies. Further research is needed to identify methods to build providers'
      perceived self-efficacy regarding these VP areas.

PMID- 17554614
TI  - Weight loss programs for urban-based, postpartum African-American women:
      perceived barriers and preferred components.
AB  - OBJECTIVES: There are currently 1.85 million reproductive-aged women in the
      United States with diabetes or glucose intolerance. While it is known that
      postpartum weight retention can lead to obesity and diabetes, particularly among
      African-American women, little is known about African-American women's
      preferences for postpartum weight loss programs. Our objective was to explore
      urban-based African-American women's attitudes toward weight gain, perceived
      barriers to postpartum weight loss, and preferences for weight intervention
      strategies. METHODS: Focus groups of pregnant African-American women (n = 22)
      were conducted by a race-concordant moderator. Open-ended questions were posed to
      stimulate discussions which were audio taped and transcribed verbatim.
      Transcriptions were independently reviewed by two investigators who extracted
      quotations and coded each statement to identify major themes. RESULTS: The median
      age of participants was 26 years. Median pre-pregnancy or first trimester body
      mass index was 31 kg/m(2). Fifty-seven percent of the women were multiparous and
      68% were Medicaid recipients. We identified 16 themes with the majority of
      participant comments focused on: (1) effect of postpartum depression on
      motivation to lose weight; (2) strong desire to lose weight; (3) knowledge of
      adverse effects of obesity; (4) costs of weight loss programs; (5) negative
      impact of media coverage of successful celebrity postpartum weight loss; (6)
      limitations of childcare on ability to exercise; and (7) family-centered
      lifestyle behaviors that promote unhealthy eating. CONCLUSIONS: Weight loss
      interventions for African-American women with postpartum obesity should address
      psychological effects of childbearing, affordability, and perceptions of body
      image. Interventions should incorporate family-centered approaches and weight
      loss maintenance strategies.

PMID- 17554616
TI  - Lack of genetic differentiation in the shrimp Penaeus chinensis in the
      Northwestern Pacific.
AB  - Genetic differentiation of the shrimp Penaeus chinensis in the Yellow Sea and
      Bohai Sea was investigated using the mitochondrial control region (CR). RFLP of a
      partial CR segment (613 bp) shows that 106 out of 122 (86.9%) individuals from
      six sampling localities along the coast of northern China and the west coast of
      the Korean Peninsula share the same haplotype, and the haplotype frequencies
      among localities are not significantly different. The findings are further
      confirmed by sequencing the complete CR. Divergence of the complete CR (992 bp)
      is less than 1.6% in 14 individuals from the six localities. F-statistics based
      on RFLP data and the TCS network of sequencing data suggest little genetic
      differentiation of P. chinensis in the Yellow Sea and Bohai Sea. Mismatch
      analysis suggests a rapid expansion of P. chinensis population to the Yellow Sea
      and the Bohai Sea, which probably occurred with the rapid rise in sea level after
      the last glacial maximum. Despite the lack of genetic heterogeneity, we propose
      that P. chinensis populations in this region should be treated as separate
      management units, as fishery management programs have to be applied on a local
      basis by different governments.

PMID- 17554615
TI  - The relation between anger coping strategies, anger mood and somatic complaints
      in children and adolescents.
AB  - Attempts to explain the experience of somatic complaints among children and
      adolescents suggest that they may in part result from the influence of particular
      strategies for coping with anger on the longevity of negative emotions. To
      explore these relationships British (n = 393) and Dutch (n = 299) children
      completed a modified version of the Behavioral Anger Response Questionnaire
      (BARQ), and two additional questionnaires assessing anger mood and somatic
      complaints. A hierarchical regression analysis showed that for both the UK and
      Dutch samples two coping styles, Social support-seeking and Rumination, made a
      significant contribution to somatic complaints, over and above the variance
      explained by anger mood. A tendency to repeatedly think or talk about an angering
      event as a way of coping seems to underlie the observed negative health effects.
      In addition, tentative support is given for a broader range of strategies to cope
      with anger than just the traditionally studied anger-out and anger-in styles.

PMID- 17554617
TI  - Genetic analysis of RET, EDNRB, and EDN3 genes and three SNPs in MCS + 9.7 in
      Chinese Patients with isolated Hirschsprung disease.

PMID- 17554618
TI  - Arg753Gln polymorphism of the human toll-like receptor-2 gene in children with
      recurrent febrile infections.
AB  - Polymorphisms in toll-like receptors (TLRs) have been reported to increase
      susceptibility for some diseases. TLR-2 gene polymorphisms in Turkish children
      with recurrent respiratory tract infections and without well-known humoral
      immunodeficiencies were examined. The study consisted of 52 children with
      recurrent infections (study group) and 91 healthy children with a maximum of two
      infections in a year (control group). Recurrent infection was defined as the
      presence of at least six febrile bacterial infection episodes in a year. Not only
      TLR-2 gene polymorphisms but also immunoglobulins (IgG, IgM, IgA), IgG subsets
      (G1, G2, G3), and specific antibody levels (anti-tetanus and anti-hemophilus
      influenza) were determined to exclude humoral immunodeficiencies. The Arg753Gln
      and Arg677Trp polymorphisms were genotyped by polymerase chain reaction
      restriction fragment length polymorphism. The Arg753Arg genotype was
      significantly decreased in the study group compared to the control (P < 0.05).
      Children with recurrent infections were also found to be more frequently
      Arg753Gln heterozygous (P < 0.05), and their Gln allele distribution was higher
      than that of the control subjects (23% vs. 4.9%; P < 0.001). In contrast to these
      results, we did not detect any case with Arg677Trp polymorphism in both groups.
      These results have indicated that there is a strong significant relationship
      between susceptibility to recurrent bacterial infections and Arg753Gln
      polymorphism of the TLR-2 gene.

PMID- 17554619
TI  - Improvement of cognitive deficit and neuronal damage in rats with chronic
      cerebral ischemia via relative long-term inhibition of rho-kinase.
AB  - (1) The role of activation of Rho-kinase in the pathogenesis of cognitive deficit
      and neuronal damage caused by chronic global ischemia is not clear. In this
      study, hydroxyfasudil, a Rho-kinase inhibitor, was found to improve the learning
      and memory performance significantly in rats with ischemia induced by chronic
      cerebral hypoperfusion after permanent bilateral carotid artery ligation (BCAL).
      This was observed by the administration of hydroxyfasudil (1 mg/kg or 10 mg/kg,
      once per day for 30 days) to ischemic rats and the measurements of escape latency
      and time spent in the target quadrant among the ischemic, sham, and ischemic plus
      hydroxyfasudil rats by the method of Morris water maze. (2) In
      electrophysiological study, hydroxyfasudil abolished the inhibition of long-term
      potentiation (LTP) in rats with ischemia. Morphologically, it also markedly
      reduced pathological changes such as neuronal cells loss and nuclei shrinkage in
      cortex and hippocampus of ischemic rats. Biochemical analysis showed that the
      inhibition of Rho-kinase by hydroxyfasudil reduced the amount of MDA and
      increased the activities of SOD and GPx in ischemic rats that had increased MDA
      and decreased SOD and GPx activities. (3) To explore mechanism (s) of the
      beneficial effects of hydroxyfasudil in ischemia, we performed
      immunohistochemistry and RT-PCR analyses of NMDA NR2B subunit and for the first
      time found that hydroxyfasudil increased the expression of NR2B in cortex and
      hippocampus at both protein and mRNA levels. (4) Taken together, our data further
      support the notion that the inhibition of Rho-kinase provides neuroprotective
      effects in cerebral ischemia.

PMID- 17554620
TI  - Multicore vesicles: hyperosmolarity and L-DOPA induce homotypic fusion of dense
      core vesicles.
AB  - AIM: A fraction of vesicles in cells treated with hypertonic solution exhibit
      multiple dense cores and this is enhanced by treatment with L-3,4
      dihydroxyphenylalanine (L-DOPA). These cells were examined to determine if the
      multicore vesicles are the product of endocytosis or homotypic fusion. METHODS:
      Electron microscopy was used to determine the number of multicore vesicles and
      amperometry was used to examine if the multicore vesicles are a competent
      fraction of the readily releasable pool. RESULTS: In this study, we observed that
      a substantial portion (15.3%) of large dense core vesicles in PC12 cells
      contained multiple cores in hypertonic saline loaded with L-DOPA, and
      amperometric measurements show a bimodal distribution of quantal sizes in treated
      cells. CONCLUSIONS: The results suggest that the multicored vesicles are formed
      from homotypic fusion of LCDVs prior to exocytosis.

PMID- 17554621
TI  - Up-regulated endogenous erythropoietin/erythropoietin receptor system and
      exogenous erythropoietin rescue retinal ganglion cells after chronic ocular
      hypertension.
AB  - AIMS: Recent studies have showed that erythropoietin (EPO) is a neuroprotectant
      for central nerve system neurons in addition to being a hematopoietic cytokine in
      response to hypoxia. In this study, we investigate the role of the EPO/EPO
      receptor (EPOR) system in the rat retina after ocular hypertension injury that
      mimics glaucoma. METHODS: Elevated intraocular pressure was induced by laser
      coagulation of the episcleral and limbal veins. Expression of EPO and EPOR in the
      normal and glaucomous retinas was investigated by immunohistochemistry and
      Western blot. To examine the effects of endogenous EPO on the survival of retinal
      ganglion cells (RGCs) subjected to hypertensive injury, soluble EPOR was directly
      injected into the vitreous body. Recombinant human EPO was both intravitreally
      and systemically administrated to study the effect of exogenous EPO on the
      survival of RGCs after ocular hypertension injury. RESULTS: Immunohistochemistry
      studies identified Muller cells as the main source of EPO in the normal retina.
      Expression of EPO and EPOR proteins was increased significantly 2 weeks after
      ocular hypertension. RGCs, amacrine and bipolar cells all demonstrated an
      increased expression of EPOR after ocular hypertension. Neutralization of
      endogenous EPO with soluble EPOR exacerbated ocular hypertensive injury,
      suggesting a role of the EPO/EPOR system in the survival of RGCs after injury.
      Similarly, topical and systemic administration of recombinant human EPO rescues
      RGCs after chronic ocular hypertension. CONCLUSIONS: These results indicate that
      an endogenous EPO/EPOR system participates in intrinsic recovery mechanisms after
      retina injury and RGCs might be rescued by exogenous administration of EPO.

PMID- 17554622
TI  - Editing of AMPA and serotonin 2C receptors in individual central neurons,
      controlling wakefulness.
AB  - (1) Pre-mRNA editing of serotonin 2C (5-HT2c) and glutamate (Glu) receptors (R)
      influences higher brain functions and pathological states such as epilepsy,
      amyotrophic lateral sclerosis, and depression. Adenosine deaminases acting on RNA
      (ADAR1-3) convert adenosine to inosine on synthetic RNAs, analogous to 5-HT2cR
      and GluR. The order of editing as well as mechanisms controlling editing in
      native neurons is unknown. (2) With single-cell RT-PCR we investigated the co
      expression of ADAR genes with GluR and 5-HT2cR and determined the editing status
      at known sites in the hypothalamic tuberomamillary nucleus, a major center for
      wakefulness and arousal. (3) The most frequently expressed enzymes were ADAR1,
      followed by ADAR2. The Q/R site of GluR2 was always fully edited. Editing at the
      R/G site in the GluR2 (but not GluR4) subunit was co-ordinated with ADAR
      expression: maximal editing was found in neurons expressing both ADAR2 splice
      variants of the deaminase domain and lacking ADAR3. (4) Editing of the 5-HT2cR
      did not correlate with ADAR expression. The 5-HT2cR mRNA was always edited at A,
      in the majority of cells at B sites and variably edited at E, C and D sites. A
      negative correlation was found between editing of C and D sites. The GluR4 R/G
      site editing was homogeneous within individuals: it was fully edited in all
      neurons obtained from 12 rats and under-edited in six neurons obtained from three
      rats. (5) We conclude that GluR2 R/G editing is controlled at the level of ADAR2
      and therefore this enzyme may be a target for pharmacotherapy. On the other hand,
      further factors/enzymes besides ADAR must control or influence 5-HT2cR and GluR
      pre-mRNA editing in native neurons; our data indicate that these factors vary
      between individuals and could be predictors of psychiatric disease.

PMID- 17554623
TI  - Resveratrol increases glutamate uptake, glutathione content, and S100B secretion
      in cortical astrocyte cultures.
AB  - Resveratrol (3,5,4'-trihydroxy-trans-stilbene) is a polyphenol present in grapes
      and red wine, which has antioxidant properties and a wide range of other
      biological effects. In this study, we investigated the effect of resveratrol, in
      a concentration range of 10-250 microM, on primary cortical astrocytes;
      evaluating cell morphology, parameters of glutamate metabolism such as glutamate
      uptake, glutamine synthetase activity and glutathione total content, and S100B
      secretion. Astrocyte cultures were prepared of cerebral cortex from neonate
      Wistar rats. Morphology was evaluated by phase-contrast microscopy and
      immunocytochemistry for glial fibrillary acidic protein (GFAP). Glutamate uptake
      was measured using L-[2,3-3H]glutamate. Glutamine synthetase and content of
      glutathione were measured by enzymatic colorimetric assays. S100B content was
      determined by ELISA. Typical polygonal morphology becomes stellated when
      astrocyte cultures were exposed to 250 microM resveratrol for 24 h. At
      concentration of 25 microM, resveratrol was able to increase glutamate uptake and
      glutathione content. Conversely, at 250 microM, resveratrol decreased glutamate
      uptake. Unexpectedly, resveratrol at this high concentration increased glutamine
      synthetase activity. Extracellular S100B increased from 50 microM upwards. Our
      findings reinforce the protective role of this compound in some brain disorders,
      particularly those involving glutamate toxicity. However, the underlying
      mechanisms of these changes are not clear at the moment and it is necessary
      caution with its administration because elevated levels of this compound could
      contribute to aggravate these conditions.

PMID- 17554624
TI  - Glucocorticoids plus opioids up-regulate genes that influence neuronal function.
AB  - (1) This study investigated the functional genomics of glucocorticoid and opioid
      receptor stimulation in cellular adaptations using a cultured neuronal cell
      model. (2) Human SH-SY5Y neuroblastoma cells grown in hormone-depleted serum were
      treated for 2-days with the glucocorticoid receptor-II agonist dexamethasone (30
      nM); the mu-opioid receptor agonist [D-Ala2, N-Me-Phe4, Gly5-ol]-Enkephalin
      acetate (DAMGO; 1 nM); or dexamethasone (30 nM) plus DAMGO (1 nM). RNA was
      extracted; purified, reverse transcribed, and labeled cDNA was hybridized to a
      10,000-oliogonucleotide-array human gene chip. Gene expression changes that were
      significantly different between treatment groups and were of interest due to
      biological function were verified by real-time reverse transcription polymerase
      chain reaction (RT-PCR). Five relevant genes were identified for which the
      combination of dexamethasone plus DAMGO, but neither one alone, significantly up
      regulated gene expression (ANOVA, P < 0.05). (3) Proteins coded by the identified
      genes: FRS2 (fibroblast growth factor receptor substrate-2; CTNNB1 (beta1
      catenin); PRCP (prolyl-carboxypeptidase); MPHOSPH9 (M-phase phosphoprotein 9);
      and ZFP95 (zinc finger protein 95) serve important neuronal functions in signal
      transduction, synapse formation, neuronal growth and development, or
      transcription regulation. Neither opioid, glucocorticoid nor combined treatments
      significantly altered the cell growth rate determined by cell counts and protein.
      (4) We conclude that sustained mu-opioid receptor stimulation accompanied by
      glucocorticoids can synergistically regulate genes that influence neuronal
      function. Future studies are warranted to determine if combined influences of
      glucocorticoid fluctuations and opioid receptor stimulation in vivo can
      orchestrate exagerated neuroadaptation to reinforcing drugs under chronic mild
      stress conditions.

PMID- 17554625
TI  - Hoxd1 is expressed by oligodendroglial cells and binds to a region of the human
      myelin oligodendrocyte glycoprotein promoter in vitro.
AB  - (1) Little information exists on the role of clustered Hox genes in
      oligodendrocyte (OG) development. This study examines the expression profile of
      Hoxd1 and identifies a potential downstream target in the OG lineage. (2)
      Immunocytochemical analysis of primary mixed glial cultures demonstrated Hoxd1
      was expressed throughout OG development. (3) A human myelin protein gene, myelin
      oligodendrocyte glycoprotein (MOG), was identified as a putative downstream
      target of Hoxdl through Genbank searches utilizing the Hoxdl homeodomain
      consensus binding sequence. (4) The dissociation coefficient constant (KD) and
      dissociation rate constant (kd) of the Hoxd1-MOG complex, determined using
      electrophoretic mobility shift assays (EMSAs), were estimated to be 1.9 x 10(-7)
      M and 1.3 x 10(-3) s(-1), respectively. The DNA-Hoxdl homeodomain complex had a
      half-life (t1/2) of 15 min. (5) Mutational analysis of Hoxd1-MOG complexes
      revealed the binding affinity of M1 (with mutation from (-1054)5'-TAAT-3'(-1051)
      to TACT within the consensus binding site) and M2 (with mutation from (-1054)5'
      TAATTG-3'(-1049) to TAATCC within the consensus binding site) probes to the MOG
      promoter was severely affected. Thus the TAATTG core of the binding sequence
      appears important for Hoxd1 specificity. (6) Analysis of the involvement of TAAT
      sites adjacent to the consensus sequence in Hoxdl binding showed the binding
      affinity of the M3 probe was affected, but not as severely as the M1 and M2
      probes. These in vitro results suggest the TTTAATTGTA sequence is involved in
      Hoxd1 binding to the MOG promoter but neighboring TAAT sites may also be needed.
      Thus, MOG may be a target of Hoxd1.

PMID- 17554627
TI  - Neutrophil gelatinase-associated lipocalin (NGAL) is a predictor of poor
      prognosis in human primary breast cancer.
AB  - Neutrophil gelatinase-associated lipocalin (NGAL) is a small, secreted
      glycoprotein with proposed functions in cell proliferation, survival and
      morphogenesis. NGAL is expressed in a variety of tumor types including breast
      carcinomas, but it is not known whether NGAL contributes directly to breast
      cancer progression. This study examines the relationship between NGAL expression
      in breast carcinomas and established clinical prognostic markers as well as
      clinical outcome. Using immunohistochemistry in tissue microarrays containing
      well characterized tumor samples from 207 breast cancer patients, NGAL was
      detected in 68 breast carcinomas in a cytoplasmic location. NGAL expression
      correlated strongly with negative steroid receptor status, HER-2/neu
      overexpression, poor histologic grade, the presence of lymph node metastases and
      a high Ki-67 proliferation index. In univariate survival analysis, NGAL
      expression was associated with decreased disease-specific survival and decreased
      disease-free survival in the entire cohort. In multivariate analysis, NGAL
      remained an independent prognostic marker for disease-free survival. In a subset
      of patients with estrogen receptor positive tumors, NGAL was significantly
      associated with decreased disease-free survival. The results show that NGAL
      expression is a predictor of poor prognosis in primary human breast cancer and
      suggest that NGAL detection may provide information for risk assessment and
      identify a subset of patients requiring more aggressive adjuvant therapy.

PMID- 17554628
TI  - Interest in breast cancer chemoprevention among older women.
AB  - OBJECTIVES: The study aim is to describe interest in breast cancer
      chemoprevention among older women without a history of breast cancer and to
      determine whether aging-related factors such as diminished life expectancy,
      increasing comorbidity and medication burden attenuate chemoprevention interest.
      DESIGN: Cross-sectional survey. SETTING: University of Pennsylvania Health
      System. PARTICIPANTS: Four-hundred fifty-seven community-dwelling women aged 60
      65 years old who were potentially eligible for breast cancer chemoprevention
      according to guidelines linking risk and eligibility to age. MEASUREMENTS:
      Interest in breast cancer chemoprevention, Gail model breast cancer risk,
      perceived breast cancer risk, breast cancer worry, self-reported health status
      and comorbidities, and self-reported perceived life expectancy. RESULTS: Of 457
      participants, 11.2% reported being interested in taking chemoprevention, 40.9%
      reported no interest, and 47.9% reported being unsure about their interest in
      chemoprevention. Overall, interest in chemoprevention was not associated with
      individual Gail model breast cancer risk. In adjusted analysis, lack of interest
      among high-risk women was associated with low breast cancer worry and low
      perceived risk. Conversely, interest in chemoprevention among low risk women was
      associated with greater breast cancer worry. Age-related factors hypothesized to
      affect chemoprevention interest, including subjective life expectancy, increased
      comorbidity, and number of daily medications did not attenuate chemoprevention
      interest. CONCLUSION: Breast cancer worry and perceived breast cancer risk
      contribute to the lack of correlation between interest in breast cancer
      chemoprevention and objective breast cancer risk. Perceived life expectancy,
      increased comorbidity, and medication burden do not attenuate chemoprevention
      interest among older women.

PMID- 17554629
TI  - HDL and its sphingosine-1-phosphate content in cardioprotection.
AB  - Increasing evidence suggests that High-density lipoproteins (HDL) are a direct
      cardioprotective agent in the setting of acute myocardial ischemia/reperfusion
      injury, and that this cardioprotection occurs independently of their
      atheroprotective effect. Studies on the involved mechanisms have revealed that
      the biologically active HDL-compound sphingosine-1-phosphate (S1P) is responsible
      for the beneficial effect of HDL on the myocardium. There appears to be an
      intricate interplay between known preconditioning agents and components of the
      S1P synthesis machinery in the heart, which makes S1P signalling an attractive
      downstream convergence point of preconditioning and cardioprotection at the level
      of its G protein-coupled receptors. While local S1P production has been known to
      protect the heart against ischemia/reperfusion injury and to mediate
      preconditioning, systemic S1P supply via HDL adds a novel aspect to the
      regulation of cardioprotection. Thus the S1P-content of HDL may serve both as a
      potential cardiovascular risk marker and a novel therapeutic target. Strategies
      for short-term "acute" HDL elevation as well as S1P analogues may prove
      beneficial not only in the high-risk patient but also in any patient at risk of
      myocardial ischemia.

PMID- 17554630
TI  - Healthcare utilization of individuals with opiate use disorders: an analysis of
      integrated medicaid and state mental health/substance abuse agency data.
AB  - Data from the Substance Abuse and Mental Health Services Administration's
      Integrated Database (IDB) were used to examine the service use patterns of
      individuals with possible opiate use disorders in Washington State. Results
      indicate that regardless of Medicaid enrollment status, individuals who received
      mental health (MH) or substance abuse (SA) services only through state agencies
      received no inpatient substance abuse service. Furthermore, when compared with
      individuals who received at least one MH/SA service through Medicaid, those who
      received services only through the state agencies were less likely to have
      received any MH services and were more likely to have received residential SA
      services. This analysis highlights the importance of using integrated client data
      in providing a more comprehensive understanding of services to inform policy and
      raises significant questions about how regulatory requirements affecting
      different funding mechanisms might drive settings of care in ways not related to
      the care needed.

PMID- 17554626
TI  - Cognitive deficits in schizophrenia: focus on neuronal nicotinic acetylcholine
      receptors and smoking.
AB  - Patients with schizophrenia present with deficits in specific areas of cognition.
      These are quantifiable by neuropsychological testing and can be clinically
      observable as negative signs. Concomitantly, they self-administer nicotine in the
      form of cigarette smoking. Nicotine dependence is more prevalent in this patient
      population when compared to other psychiatric conditions or to non-mentally ill
      people. The target for nicotine is the neuronal nicotinic acetylcholine receptor
      (nAChR). There is ample evidence that these receptors are involved in normal
      cognitive operations within the brain. This review describes neuronal nAChR
      structure and function, focusing on both cholinergic agonist-induced nAChR
      desensitization and nAChR up-regulation. The several mechanisms proposed for the
      nAChR up-regulation are examined in detail. Desensitization and up-regulation of
      nAChRs may be relevant to the physiopathology of schizophrenia. The participation
      of several subtypes of neuronal nAChRs in the cognitive processing of non
      mentally ill persons and schizophrenic patients is reviewed. The role of smoking
      is then examined as a possible cognitive remediator in this psychiatric
      condition. Finally, pharmacological strategies focused on neuronal nAChRs are
      discussed as possible therapeutic avenues that may ameliorate the cognitive
      deficits of schizophrenia.

PMID- 17554631
TI  - Incidence of the endosymbionts Wolbachia, Cardinium and Spiroplasma in phytoseiid
      mites and associated prey.
AB  - Endosymbiotic bacteria that potentially influence reproduction and other fitness
      related traits of their hosts are widespread in insects and mites and their
      appeal to researchers' interest is still increasing. We screened 20 strains of 12
      agriculturally relevant herbivorous and predatory mite species for infection with
      Wolbachia, Cardinium and Spiroplasma by the use of PCR. The majority of specimens
      originated from Austria and were field collected or mass-reared. Eight out of 20
      strains (40%) tested, representing seven of 12 mite species (58%), carried at
      least one of the three bacteria. We found Wolbachia in the herbivorous spider
      mites Tetranychus urticae and Bryobia rubrioculus, with the former also carrying
      Spiroplasma and the latter also carrying Cardinium. Cardinium was furthermore
      found in two populations of the predatory mite Euseius finlandicus and the spider
      mite Eotetranychus uncatus. Spiroplasma was detected in the predatory mite
      Neoseiulus californicus. All bacteria positive PCR products were sequenced,
      submitted to GenBank and analyzed in BLAST queries. We found high similarities to
      complete identity with bacteria found in the same and different mite species but
      also with bacteria found in insect species like ladybirds, butterflies and minute
      pirate bugs, Orius. We discuss the significance of potential (multiple)
      infections with the investigated bacteria for biological control.

PMID- 17554632
TI  - GABA and glutamate signaling: homeostatic control of adult forebrain
      neurogenesis.
AB  - The neurotransmitter GABA exerts a strong negative influence on the production of
      adult-born olfactory bulb interneurons via tightly regulated, non-synaptic
      GABAergic signaling. After discussing some findings on GABAergic signaling in the
      neurogenic subventricular zone (SVZ), we provide data suggesting ambient GABA
      clearance via two GABA transporter subtypes and further support for a non
      vesicular mechanism of GABA release from neuroblasts. While GABA works in
      cooperation with the neurotransmitter glutamate during embryonic cortical
      development, the role of glutamate in adult forebrain neurogenesis remains
      obscure. Only one of the eight metabotropic glutamate receptors (mGluRs), mGluR5,
      has been reported to tonically increase the number of proliferative SVZ cells in
      vivo, suggesting a local source of glutamate in the SVZ. We show here that
      glutamate antibodies strongly label subventricular zone (SVZ) astrocytes, some of
      which are stem cells. We also show that some SVZ neuroblasts express one of the
      ionotropic glutamate receptors, AMPA/kainate receptors, earlier than previously
      thought. Collectively, these findings suggest that neuroblast-to-astrocyte
      GABAergic signaling may cooperate with astrocyte-to-neuroblast glutamatergic
      signaling to provide strong homeostatic control on the production of adult-born
      olfactory bulb interneurons.

PMID- 17554633
TI  - Myeloma cast nephropathy presenting as acute onset bilateral reversible hearing
      loss.
AB  - A case of myeloma cast nephropathy masquerading as bilateral deafness of acute
      onset, probably due to hyperviscosity syndrome, is presented. Audiometry and
      kidney biopsy confirmed the diagnosis. Despite the presence of multiple poor
      prognostic features, the patient responded satisfactorily to plasmapharesis,
      dialysis and chemotherapy (VAD regimen) along with other supportive measures. The
      patient had excellent renal recovery, but hearing improvement was delayed for 1
      month. Various causes of hearing loss in patients with multiple myeloma and
      available therapeutic options are discussed.

PMID- 17554634
TI  - Application of low temperatures during photoinhibition allows characterization of
      individual steps in photodamage and the repair of photosystem II.
AB  - Recent investigations of photoinhibition have revealed that photodamage to
      photosystem II (PSII) involves two temporally separated steps: the first is the
      inactivation of the oxygen-evolving complex by light that has been absorbed by
      the manganese cluster and the second is the impairment of the photochemical
      reaction center by light that has been absorbed by chlorophyll. Our studies of
      photoinhibition in Synechocystis sp. PCC 6803 at various temperatures
      demonstrated that the first step in photodamage is not completed at low
      temperatures, such as 10 degrees C. Further investigations suggested that an
      intermediate state, which is stabilized at low temperatures, might exist at the
      first stage of photodamage. The repair of PSII involves many steps, including
      degradation and removal of the D1 protein, synthesis de novo of the precursor to
      the D1 protein, assembly of the PSII complex, and processing of the precursor to
      the D1 protein. Detailed analysis of photodamage and repair at various
      temperatures has demonstrated that, among these steps, only the synthesis of the
      precursor to D1 appears to proceed at low temperatures. Investigations of
      photoinhibition at low temperatures have also indicated that prolonged exposure
      of cyanobacterial cells or plant leaves to strong light diminishes their ability
      to repair PSII. Such non-repairable photoinhibition is caused by inhibition of
      the processing of the precursor to the D1 protein after prolonged illumination
      with strong light at low temperatures.

PMID- 17554635
TI  - A Synechococcus elongatus PCC 7942 mutant with a higher tolerance toward the
      herbicide bentazone also confers resistance to sodium chloride stress.
AB  - Following a N-methyl-N'-nitro-N-nitrosoguanidine-based mutagenesis of
      Synechococcus elongatus PCC 7942 wild type, we were able to select several
      mutants with an enhanced tolerance toward the herbicide bentazone (3-isopropyl-1H
      2,1,3-benzothiadiazine-4(3H)-one 2,2-dioxide). Mutant Mu1 has in part been
      previously characterized. In the present paper we report on another mutant,
      called Mu2, which also has a higher tolerance toward bentazone. Since Mu2 showed
      a better growth than WT when cultivated with elevated NaCl concentrations in the
      growth medium and since S. elongatus WT has previously been classified to be low
      salt tolerant, we were especially interested in the identification of the
      modifications conferring this higher salt tolerance to mutant Mu2. Immunoblot
      analyses provided evidence that Mu2 had a constitutively higher expression of
      PsbO and of IsiA. In addition, in Mu2 a significantly higher concentration of
      IdiA was detected under salt stress as compared to WT. These three proteins most
      likely contribute to a better protection and/or stabilization of photosystem II.
      Moreover, Mu2 had a higher amount of the photosystem I reaction center proteins
      PsaAB under salt stress than WT. In addition, the amount of the ferredoxin:NADP+
      oxidoreductase and also of the ATP synthase was constitutively higher in Mu2 than
      in WT. In contrast to WT the latter two proteins did not decrease under salt
      stress in Mu2. Therefore, it can be assumed that Mu2 could maintain a high cyclic
      electron transport activity around photosystem I under salt stress. It can be
      assumed that the combination of these modifications of the electron transport
      chain cause a better protection of photosystem II against oxidative damage and
      cause an increase of cyclic electron transport activity around photosystem I with
      ATP synthesis. Thus, the overall cellular energization in Mu2 relative to WT is
      improved. Together with putative other not yet identified modifications this
      seems to enable Mu2 to energize its cytoplasmic membrane-localized ion pumps more
      effectively than WT and, as a consequence, to keep the intracellular NaCl
      concentration low.

PMID- 17554636
TI  - Error-reducing structure of the genetic code indicates code origin in non
      thermophile organisms.
AB  - During the RNA World, organisms experienced high rates of genetic errors, which
      implies that there was strong evolutionary pressure to reduce the errors'
      phenotypical impact by suitably structuring the still-evolving genetic code.
      Therefore, the relative rates of the various types of genetic errors should have
      left characteristic imprints in the structure of the genetic code. Here, we show
      that, therefore, it is possible to some extent to reconstruct those error rates,
      as well as the nucleotide frequencies, for the time when the code was fixed. We
      find evidence indicating that the frequencies of G and C in the genome were not
      elevated. Since, for thermodynamic reasons, RNA in thermophiles tends to possess
      elevated G+C content, this result indicates that the fixation of the genetic code
      occurred in organisms which were either not thermophiles or that the code's
      fixation occurred after the rise of DNA.

PMID- 17554637
TI  - Review of innate and specific immunity in plants and animals.
AB  - Innate immunity represents a trait common to plants and animals, based on the
      recognition of pathogen associated molecular patterns (PAMPs) by the host pattern
      recognition receptors (PRRs). It is generally assumed that a pathogen strain, or
      race, may have elaborated mechanisms to suppress, or evade, the PAMP-triggered
      immunity. Once this plan was successful, the colonization would have been
      counteracted by an adaptive strategy that a plant cultivar must have evolved as a
      second line of defence. In this co-evolutionary context, adaptive immunity and
      host resistance (cultivar-pathogen race/strain-specific) has been differently
      selected, in animals and plants respectively, to face specialized pathogens.
      Notwithstanding, plant host resistance, based on matching between resistance (R)
      and avirulence (avr) genes, represents a form of innate immunity, being R
      proteins similar to PRRs, although able to recognize specific virulence factors
      (avr proteins) rather than PAMPs. Besides, despite the lack of adaptive immunity
      preserved plants from autoimmune disorders, inappropriate plant immune responses
      may occur, producing some side-effects, in terms of fitness costs of induced
      resistance and autotoxicity. A set of similar defence responses shared from
      plants and animals, such as defensins, reactive oxygen species (ROS), oxylipins
      and programmed cell death (PCD) are briefly described.

PMID- 17554638
TI  - Gastrointestinal zygomycosis: a report of three cases.
AB  - Three cases of gastrointestinal zygomycosis, probably caused by Basidiobolus
      ranarum, are described. The diagnosis was based on morphology of the fungal
      elements in infected tissues and histopathologic findings. All the three patients
      responded favorably to management strategy that included surgical resection of
      the infected portion of the bowel and institution of specific antifungal therapy.

PMID- 17554639
TI  - Genotyping of Trichophyton rubrum by analysis of ribosomal-DNA intergenic spacer
      regions.
AB  - An attempt was made to explore the genotyping of Trichophyton rubrum (T. rubrum)
      and the relationship between genotype and geographical origin using ribosomal
      restriction endonuclease polymorphic analysis. The total DNA was extracted by
      cetyltrimethyl ammonium bromide (CTAB). The probe was amplified from part of the
      18S, ITSI, 5.8S, and ITSII region of T. rubrum standard strain with the universal
      fungal primers NS5 [5'-AACTT AAAGG AATTG ACGGA AG-3'] and ITS4 [5'-TCCTC CGCTT
      ATTGA TATGC-3']. The genomic DNA of 49 clinical T. rubrum isolates digested by
      EcoR1 were hybridized with this probe, and the hybridization patterns were used
      as the basis of genotyping. Of the data from 49 strains of T. rubrum studied (21
      from Nanjing, 26 from Dalian, and two from Beijing), 20 individual patterns (DNA
      Type A-T) were identified, among which Type A-C accounted for 48.98% of all the
      strains. The DNA patterns of Nanjing strains were represented by three bands,
      those of Dalian strains were represented by four bands. The DNA typing of T.
      rubrum by Southern blotting was highly sensitive and highly distinguishable. The
      DNA patterns of Nanjing strains were obviously different from those of Dalian
      strains.

PMID- 17554640
TI  - A comparison of three sets of criteria for determining the presence of
      differential item functioning using ordinal logistic regression.
AB  - BACKGROUND: Several techniques have been developed to detect differential item
      functioning (DIF), including ordinal logistic regression (OLR). This study
      compared different criteria for determining whether items have DIF using OLR.
      OBJECTIVES: To compare and contrast findings from three different sets of
      criteria for detecting DIF using OLR. General distress and physical functioning
      items were evaluated for DIF related to five covariates: age, marital status,
      gender, race, and Hispanic origin. RESEARCH DESIGN: Cross-sectional study.
      SUBJECTS: 1,714 patients with cancer or HIV/AIDS. MEASURES: A total of 23 items
      addressing physical functioning and 15 items addressing general distress were
      selected from a pool of 154 items from four different health-related quality of
      life questionnaires. RESULTS: The three sets of criteria produced qualitatively
      and quantitatively different results. Criteria based on statistical significance
      alone detected DIF in almost all the items, while alternative criteria based on
      magnitude detected DIF in far fewer items. Accounting for DIF by using
      demographic-group specific item parameters had negligible effects on individual
      scores, except for race. CONCLUSIONS: Specific criteria chosen to determine
      whether items have DIF have an impact on the findings. Criteria based entirely on
      statistical significance may detect small differences that are clinically
      negligible.

PMID- 17554641
TI  - [Prophylaxis, Diagnosis and Therapy of Hepatitis-B-Virus-(HBV-)Infection: upgrade
      of the guideline, AWMF-Register 021/011].

PMID- 17554642
TI  - Evaluation of endocytoscopy in the surveillance of patients with Barrett's
      esophagus.
AB  - BACKGROUND AND STUDY AIMS: Surveillance for patients with Barrett's esophagus is
      time consuming and subject to sampling error. Guided biopsies from neoplastic
      areas invisible on conventional endoscopy may increase effectiveness of
      surveillance examination. We assessed the accuracy of endocytoscopy in
      correlation with histology. METHODS: We analyzed 166 biopsy sites from 16
      patients (13 male, mean age 62.1 years), without visible lesions, who presented
      for Barrett surveillance. Endocytoscopy images were recorded from pre-marked
      areas in the Barrett's segment using magnification x 1125 or x 450. Biopsies were
      taken from the same area to allow precise comparison with histology. Image
      sequences of each area were individually and blindly reviewed by a pathologist
      and a gastroenterologist. Major outcome variables included image quality,
      identification of neoplastic characteristics, and accuracy of endocytoscopy.
      RESULTS: Adenocarcinoma was histologically diagnosed in 4.2% of biopsy sites,
      high grade intraepithelial neoplasia (HGIN) in 16.9%, and low grade
      intraepithelial neoplasia (LGIN) in 12.1 %. Adequate assessment of endocytoscopy
      images was impossible in 49% of the pre-marked areas with magnification x 450 and
      in 22% with magnification x 1125. At most, 23% of images with lower magnification
      were interpretable to identify characteristics of neoplasia, and 41% with higher
      magnification. Interobserver agreement was fair at best (kappa from < 0 to 0.45).
      Positive and negative predictive values for HGIN or cancer were 0.29 and 0.87,
      respectively, for magnification x 450 and 0.44 and 0.83, respectively, for
      magnification x 1125. CONCLUSION: When not supported by macroscopic evidence,
      endoscopic histology using endocytoscopy lacks sufficient image quality to be
      currently of assistance in identifying neoplastic areas.

PMID- 17554643
TI  - Can an endocytoscope system (ECS) predict histology in neoplastic lesions?
AB  - BACKGROUND AND STUDY AIMS: An endocytoscope system (ECS) has recently been
      developed with the possibility of super-high magnification of gastrointestinal
      mucosa, thus allowing in vivo imaging of living cells. The aim of the present
      study was to assess the potential of ECS in the prediction of histology in both
      normal gastrointestinal mucosa and neoplastic lesions. PATIENTS AND METHODS: In
      total, 76 patients (57 men, 19 women; age range 37-86 years) with neoplastic
      lesions in the esophagus, stomach, or colon were enrolled into the study and
      underwent esophagogastroduodenoscopy or colonoscopy. After staining with 1%
      methylene blue, the mucosa was examined with the ECS probe (x 450 and x 1100
      magnification), and video sequences were recorded on video disk. Biopsies from
      the examined areas were taken for histology and served as the gold standard. The
      endocytoscope video sequences were evaluated by two blinded pathologists. Finally
      the results were compared with those resulting from the evaluation of an
      experienced endoscopist who was aware of the macroscopic endoscopic pictures and
      the endocytoscope image results. RESULTS: A total of 25 patients with esophageal
      lesions, 28 patients with colonic lesions, and 23 patients with gastric lesions
      were examined. The sensitivity and specificity for the evaluation of the blinded
      pathologists was 81% and 100%, respectively, in the esophagus, 56% and 89% in the
      stomach, and 79% and 90% in the colon. If an endoscopist evaluated the
      endocytoscopic pictures in combination with the macroscopic endoscopic images
      sensitivity and specificity increased significantly. CONCLUSIONS: First
      experiences with ECS show good sensitivity rates even by blinded assessment for
      esophageal and colonic lesions. Sensitivity for neoplastic lesions in the stomach
      is lower because of gastric mucous secretion. Combining the endoscopic and
      cytoscopic appearance of the lesion may further enhance the diagnostic value of
      the method.

PMID- 17554644
TI  - Music in the endoscopy suite: a meta-analysis of randomized controlled studies.
AB  - BACKGROUND AND STUDY AIM: Prior studies have suggested that music therapy can
      provide stress relief and analgesia. In this meta-analysis we focused on the
      effects of music therapy on patients undergoing gastrointestinal endoscopic
      procedures. MATERIALS AND METHODS: A literature search using the PubMed and
      Cochrane Library databases and a manual search led to the inclusion of six
      randomized controlled trials that examined the effects of music therapy on
      patients undergoing gastrointestinal endoscopic procedures. After data
      extraction, four separate meta-analyses were performed: in the three studies that
      did not use pharmacotherapy (group A), anxiety levels were used as a measure of
      efficacy; in the three studies in which pharmacotherapy was used (group B),
      sedation and analgesia requirements and procedure duration times were analyzed.
      RESULTS: A total of 641 patients were included in the analysis. In group A,
      patients receiving music therapy exhibited lower anxiety levels (8.6% reduction,
      P = 0.004), compared with controls. In group B, patients receiving music therapy
      exhibited statistically significant reductions in analgesia requirements (29.7%
      reduction, P = 0.001) and procedure times (21% reduction, P = 0.002), and a
      reduction in sedation requirements that approached significance (15% reduction, P
      = 0.055), in comparison with controls. CONCLUSIONS: Music therapy is an effective
      tool for stress relief and analgesia in patients undergoing gastrointestinal
      endoscopic procedures.

PMID- 17554645
TI  - The role of double-balloon enteroscopy in diagnosis and management of incomplete
      small-bowel obstruction.
AB  - BACKGROUND AND STUDY AIMS: Double-balloon enteroscopy (DBE) is a newly developed
      endoscopic technique for investigating various small-bowel diseases. The aim of
      this study was to evaluate the diagnostic yield and therapeutic impact of DBE in
      patients with incomplete small-bowel obstruction (SBO). PATIENTS AND METHODS:
      This study is a prospective analysis of 45 consecutive patients specifically
      referred to our hospital between December 2004 and January 2006 for investigation
      of incomplete SBO that had been confirmed by both clinical symptoms and imaging
      tests. Patients with a high suspicion of postoperative adhesion were excluded and
      DBE was performed in stable patients. The final management was guided by the
      results of DBE and radiographic studies. Demographic, clinical, procedural, and
      outcome data were collected for analysis. RESULTS: A total of 30 DBEs were
      performed in 29 patients (11 women, 18 men; mean age 52.0 +/- 13.5 years). DBE
      identified causes of incomplete SBO in 27 patients (93.1%) and allowed
      histopathologic evaluation in 17 patients (58.6%). The more common abnormalities
      detected were small-bowel tumors (48.3%) and strictures caused by Crohn's disease
      (24.1%). In detecting small-bowel abnormalities, DBE showed a sensitivity of
      96.4%, a specificity of 100%, a positive predictive value of 100%, and a negative
      predictive value of 50%. DBE influenced the therapeutic strategy in 41.4% of
      patients by adding more information regarding appropriate treatment. Follow-up
      data were obtained for 26 patients (89.7%), for a mean 9.4 months (range 4-18
      months). Of the 26 patients with follow-up, 21 (72.4%) had no further SBO.
      CONCLUSIONS: Double-balloon enteroscopy is a feasible diagnostic tool for
      detecting the causes of incomplete SBO in patients without a history of abdominal
      surgery and also influences therapy in patients without a definite cause detected
      by conventional radiography.

PMID- 17554646
TI  - Evaluation of patients with hereditary hemorrhagic telangiectasia with video
      capsule endoscopy: a single-center prospective study.
AB  - BACKGROUND AND STUDY AIMS: Hereditary hemorrhagic telangiectasia (HHT) is a rare
      autosomal dominant disorder characterized by telangiectasia formation that can
      lead to small-bowel bleeding. In this study, video capsule endoscopy was used to
      compare the small-bowel findings observed in patients with HHT with those seen in
      patients without the condition. PATIENTS AND METHODS: We performed capsule
      endoscopy studies in 93 consecutive patients who were being evaluated for small
      bowel bleeding, 38 patients with known or suspected HHT and 55 patients without
      HHT. Nine patients were excluded because the capsule failed to reach the cecum.
      The findings in 32 patients with a final diagnosis of HHT and in 48 patients
      without HHT were recorded and compared. RESULTS: Capsule endoscopy detected
      telangiectases evenly distributed throughout the small bowel in 26/32 (81%)
      patients with HHT, compared with 14/48 (29%) in patients without HHT. When active
      bleeding was observed in patients with HHT (n = 4), the bleeding was within reach
      of standard small-bowel push enteroscopy in all cases. The presence of five or
      more gastrointestinal telangiectases by capsule endoscopy had a sensitivity of
      75% and a positive predictive value of 86% for diagnosing HHT. Unexpected
      findings (small-bowel polyps and mass-like lesions) were seen in both groups of
      patients (6.2% in patients with HHT and 2.1% in patients without HHT).
      CONCLUSIONS: Small-bowel telangiectases were seen in the majority of patients
      with HHT and were evenly distributed throughout the small bowel. Telangiectases
      were observed in only a minority of patients who did not have HHT. Actively
      bleeding small-bowel telangiectases were located in the proximal and mid-small
      bowel in patients with HHT, all within reach of an enteroscope. We propose a
      cutoff point of at least five gastrointestinal telangiectases to support a
      diagnosis of HHT.

PMID- 17554647
TI  - The feasibility and risk of early colonoscopy in acute diverticulitis: a
      prospective controlled study.
AB  - BACKGROUND AND STUDY AIM: Following acute diverticulitis, colonoscopy is advised
      to rule out malignancy. Commonly, the colonoscopy is postponed to avoid the
      potential risk of perforation. In a previous pilot, noncontrolled study, we
      showed that early colonoscopy is feasible in patients with acute diverticulitis.
      This randomized controlled trial compared early and late colonoscopy in
      hospitalized patients with acute diverticulitis. PATIENTS AND METHODS: 154
      patients diagnosed with acute diverticulitis were hospitalized between January
      2004 and June 2006. Of these, 35 patients were excluded because of either free
      perforation or pericolic air on computed tomography (CT), and another 18 because
      they had undergone colonoscopy in the previous year. The remaining 101 patients
      were offered the possibility of participating in the study, with random
      allocation to either early in-hospital colonoscopy or late colonoscopy, 6 weeks
      later. Randomization was refused by 15 patients, and 86 were included in the
      study. RESULTS: 45 patients were randomly allocated for early colonoscopy and 41
      for late colonoscopy. Three and 10 did not present for the examination, in the
      early and late group respectively. The cecum could not be reached in eight and
      three patients from the early and late groups, respectively. The colonoscopy
      revealed polyps in five patients, two in the early group and three in the late
      group. No malignancy was detected. There were no complications in either group.
      CONCLUSIONS: Early colonoscopy in acute diverticulitis is feasible and safe in
      the absence of pericolic air on CT, and has greater compliance. However, no added
      value is apparent compared with the CT scan currently used.

PMID- 17554649
TI  - Endoscopic ultrasound-guided interstitial chemotherapy in the pancreas: results
      in a canine model.
AB  - BACKGROUND AND STUDY AIM: Interstitial chemotherapy using surgically implanted,
      biodegradable polymers has been reported. Our aim in this study was to
      investigate the feasibility and safety of endoscopic ultrasound- (EUS-) guided
      interstitial chemotherapy of the pancreas in a canine model. MATERIALS AND
      METHODS: A therapeutic 19-gauge needle with a large channel was inserted into the
      pancreas under EUS guidance. The polymers for sustained intratumoral release of 5
      fluorouracil were implanted into the tissue by the needle. After 14 days of
      clinical observation, the animals were sacrificed and the tissue response to the
      local chemotherapy was examined. RESULTS: All the polymers were implanted
      successfully and no implant migration occurred. Localized tissue fibrous necrosis
      was achieved in the pancreas, without significant complications. The apoptotic
      index of the tissue within 1 cm of the focus increased. Biochemical parameters
      were normal in all the dogs. CONCLUSIONS: EUS-guided implantation of polymers is
      a safe, simple, and minimally invasive technique for interstitial chemotherapy in
      the pancreas.

PMID- 17554648
TI  - The utility of contrast-enhanced endoscopic ultrasound in monitoring ethanol
      induced pancreatic tissue ablation: a pilot study in a porcine model.
AB  - BACKGROUND AND STUDY AIMS: Pancreatic ablation is gaining popularity for the
      treatment of focal pancreatic lesions. The aim of our study was to evaluate local
      effects of intrapancreatic alcohol injection and the utility of contrast-enhanced
      endoscopic ultrasound (EUS) for its monitoring in a porcine model. METHODS: We
      performed four survival experiments on 50-kg pigs. Under linear EUS guidance, 0.5
      mL of 50% ethanol plus purified carbon particle solution (GI Spot) was injected
      into the pancreatic body to create a focal area of pancreatic necrosis. The
      animals survived for 24-48 hours (pigs # 1, # 2, and # 3) and 7 days (pig # 4).
      EUS was then repeated with and without perflutren lipid microspheres (Definity)
      administration through the peripheral vein. Standard and microsphere-enhanced
      images of the pancreas were compared. Afterwards the animals were euthanized for
      necropsy. RESULTS: Alcohol injection caused focal pancreatic necrosis, which was
      barely seen by standard EUS as a subtle hypoechoic lesion 1 cm in diameter. Color
      and power Doppler EUS of this region did not reveal any blood flow. After
      intravenous injection of microspheres, color Doppler EUS revealed marked contrast
      enhancement of normal pancreatic parenchyma with a clearly delineated avascular
      alcohol-treated area, which on postmortem examination corresponded to the
      discrete necrotic area marked with carbon particles. CONCLUSIONS: EUS-guided
      alcohol injection consistently causes focal areas of pancreatic necrosis.
      Contrast-enhanced EUS with microspheres improves visualization of altered
      pancreatic vascular perfusion and can be used to facilitate detection of small
      pancreatic lesions and its follow-up post-ablation.

PMID- 17554650
TI  - EUS training in a live pig model: does it improve echo endoscope hands-on and
      trainee competence?
AB  - BACKGROUND AND STUDY AIM: The learning curve for endoscopic ultrasonography (EUS)
      is known to be difficult, especially in the field of pancreatic and biliary
      diseases. The aim of this study was to assess the impact of a live pig model
      developed for EUS credentialing in France. METHODS: A total of 17 trainees
      obtained hands-on EUS experience using a live pig model. Trainees were asked to
      visualize anatomical structures, to carry out fine-needle aspiration (FNA) on
      lymph nodes in the liver hilum, and to perform celiac neurolysis. Assessment of
      the FNA procedure or celiac neurolysis included measurement of time (seconds),
      evaluation of the precision of the puncture (mm), and existence of technical
      errors. RESULTS: A significant improvement between a pre-test and post-test was
      observed for diagnostic procedures in the following anatomical areas: splenic
      mesenteric vein, vena cava, splenic mesenteric artery, celiac tree, pancreatic
      gland, and bile duct. For lymph node FNA, a significant improvement was observed
      in the duration of the procedure (84 seconds vs. 60 seconds; P = 0.01), and
      precision (4.2 mm vs. 1.8 mm; P = 0.009), but not for the rate of technical error
      (29% vs. 6%; not significant [n. s.]). For celiac neurolysis, a significant
      improvement was observed in procedure time (150 seconds vs. 84 seconds; P =
      0.003), but not in the rate of technical error (6% vs. 6%; n. s.) or precision
      (4.2 mm vs. 2.8 mm; n. s.). CONCLUSION: Teaching EUS with a live pig model
      significantly increased competence in diagnostic procedures with regard to
      visualizing anatomical structures, performance of FNA and, to a lesser extent,
      EUS-guided celiac neurolysis.

PMID- 17554651
TI  - Endoscopy to endocytoscopy to endopathology: are we ready?

PMID- 17554652
TI  - CT colonoscopy in 2007: the next standard for colorectal cancer screening in
      average-risk subjects?

PMID- 17554653
TI  - Computed tomographic colonography for colorectal screening.
AB  - Computed tomographic colonography (CTC) is a specialized computed tomographic
      examination that has been optimized for the detection of colorectal polyps. The
      technology has undergone major advances in recent years and there is emerging
      consensus that state-of-the-art CTC results in performance characteristics
      comparable to those of optical colonoscopy for polyps > or = 8 mm in size.
      Effective polyp detection rests on the quality of several components of the
      examination, which must all be optimized in order to maintain appropriate
      sensitivity and specificity, including adequate bowel preparation, good colonic
      distension, sufficient scanning parameters, and appropriate interpretation. The
      emergence of CTC provides another method of colonic evaluation for colorectal
      cancer screening and prevention. In contrast to a mutually exclusive approach to
      screening, the availability of both optical colonoscopy and CTC should hopefully
      improve overall compliance rates for colorectal screening. The ultimate role of
      this technique in the screening program continues to evolve. There is currently
      considerable variability in the materials and methods used in CTC. This article
      describes the approach used at the University of Wisconsin, which has been
      validated in a large multicenter screening trial and which is currently used for
      an active CTC-based colorectal cancer screening program.

PMID- 17554654
TI  - Esophageal cancer: cases and causes (part I).

PMID- 17554655
TI  - Ethical issues in endoscopy: patient satisfaction, safety in elderly patients,
      palliation, and relations with industry. Second European Symposium on Ethics in
      Gastroenterology and Digestive Endoscopy, Kos, Greece, July 2006.

PMID- 17554656
TI  - Grasping-forceps-assisted endoscopic submucosal dissection using a novel
      irrigation cap-knife for large superficial early gastric cancer.
AB  - The technique of endoscopic submucosal dissection (ESD) needs special skills and
      involves a long procedure. We therefore developed a new type of dissection knife,
      the irrigation cap-knife (the Kume cap-knife attachment, which uses a fixed
      snare), that facilitates ESD by just sliding over the muscle layer with a
      coagulating current. The ESD procedure using the irrigation cap-knife was
      performed in seven patients with intramucosal gastric cancer. The tumor was
      separated from the surrounding normal mucosa using the insulated-tip knife.
      Submucosal dissection was then performed by pushing our device along the muscle
      layer while applying a coagulating current, at the same time as a grasping
      forceps, deployed through the accessory channel, was used to push the lesion away
      from the muscle layer. The rate of en bloc resection was 100% (7/7). The
      irrigating cap-knife was extremely useful for ESD of large intramucosal cancers
      in the stomach.

PMID- 17554657
TI  - Open-biopsy-forceps technique for removing biliary metallic stents that have
      migrated distally and wedged transversely in the duodenum.

PMID- 17554658
TI  - Diagnostic approach to a patient with atypical Henoch-Schonlein purpura.

PMID- 17554660
TI  - Endoscopy and small-bowel biopsy in celiac disease: indications and implications.

PMID- 17554663
TI  - [Researching subordinate personality atavism in schizophrenia from the
      perspective of physical, mental and spiritual healing, and helping the patient to
      recover].
AB  - Schizophrenia is not an incurable condition. If we had not understood the
      operating model of schizophrenia in its spiritual phase, we would not know what
      its causes were, and there would be no cure for it. The author has studied The
      Seth Material for more than twenty years. New Age thinking has it that
      schizophrenia can be redefined as a phenomenon of subordinate personality or
      secondary personality. This new definition has directly pointed out and solved
      the core problems of schizophrenia. It has provided a perfect explanation of
      phenomenology. Also, the etiology of schizophrenia has been built. A guide to
      diagnosis and the new treatment has been produced. The secondary personality, as
      described above, prevents the patient from being willing to face and grow with
      his main personality, and causes him to split from it. A new vision of mind and
      spirit enables a schizophrenic episode to be seen in fact as a process which
      forces him to face himself and push him to grow into one and self-heal. According
      to the symptoms of schizophrenia (auditory hallucinations, thought withdrawal,
      insertion and interruption, thought broadcasting, somatic hallucinations,
      delusional perception, external agents), which are the key points of recovery,
      the author proposes the theory of recorder as a spiritual prescription for
      healing which has succeeded in helping our patients.

PMID- 17554664
TI  - [Huan-Ting: the core of holistic health].
AB  - The holistic person encompasses the body, mind and spirit. The core of holistic
      health is Huan-Ting, the "inner source of the heart" - a term used to describe
      the mind and spirit. The heart is the repository of feelings in the human body,
      the source of feelings of joy, pain, excitement, desire, anxiety, and soon. These
      feelings are the essence of life. Many people want to take a closer look at these
      feelings in order to better understand or to cleanse them. But where in our heart
      should we look? Modern science anticipates that all phenomena in our bodies must
      have an exact location. A dentist, for example, must find the location of a
      toothache. Otherwise, how can he or she treat it? Likewise, when we have pain or
      anxiety in our heart, it should also be associated with a precise position. One
      Buddhist saying claims that "Buddhism points to one's heart" while another states
      that, "the heart is everywhere." They seem to contradict each other. Are they
      talking about the same thing? On the road to find the inner source of the heart,
      are we overlooking something that makes finding it even more difficult? The
      purpose of the paper is to reveal and better understand "Huan-Ting", the core of
      health of body-mind-spirit health.

PMID- 17554665
TI  - [A view of holistic health].
AB  - Rather than discuss how to conduct holistic health, this article seeks to view
      holistic health from a distance. First of all, it looks back at examples of the
      terms, "holistic," and, "health," that appear in history, and shows the evolution
      of the "health concept." Secondly, it focuses on the WHO's definition of health -
      "a state of complete physical, mental and social well-being" paying special
      attention to social wellbeing. By observing the symptoms of the medicalized
      society, it considers the possibility of conducting holistic health.

PMID- 17554666
TI  - [Teaching patient-centered holistic care].
AB  - Nursing education aims to help students understand concepts and gain competencies
      in holistic care. The purpose of this paper was to present a nursing curriculum
      that adapted and introduced holistic care into an adult nursing curriculum taught
      at a university of science and technology. The course framework included both
      holistic and nursing domains. The holistic aspect addressed client physical
      psychological-spiritual needs and related factors, health related factors, and
      the status of Maslow's hierarchy of needs and related factors. The nursing aspect
      addressed the way in which nursing was applied to identify client problems and
      provide individualized, integrated and continuous care in hospital, family or
      community based settings employing primary, secondary, or tertiary prevention.
      Scenario with problem based learning and concept mapping were used in class to
      guide students to consider in depth the concepts that underpin holistic care.

PMID- 17554667
TI  - [Activities of daily living, quality of life and related factors in cachectic
      gastrointestinal cancer patients].
AB  - Cancer is the leading cause of death in Taiwan. Cachexia, which causes
      significant weight loss and malnutrition, is a common complication and one of the
      major causes of death in advanced cancer patients. The purpose of this study was
      to explore the association between personal characteristics, nutritional status,
      activities of daily living (ADL) and quality of life (QOL) in 40 cachectic
      gastrointestinal tract cancer (GI cancer) patients in southern Taiwan. A
      descriptive correlation study design and three structured questionnaires
      (including the Personal Characteristics, Index of Self-Report ADL and WHOQOL
      BREF) were used. Nutritional status was assessed by measurement of body weight
      and triceps skin-fold thickness. The results showed that: (1) The mean ADL score
      was 65.73 out of 77, a medium-high score. (2) The standardized QOL score was
      58.71, a medium score, with the highest score in the social relationships domain
      and the lowest score in the physical health domain. (3) There were some
      significant differences and correlations to the ADL were age and percentage of
      body weight loss; (4) there were some significant differences and correlations to
      the QOL were employment, the level of the physical symptoms influence and %IBW;
      (5) ADL was significantly correlated to the QOL, physical health domain and
      environment domain. The results indicate that in addition to providing symptoms
      management and care, the health care team should also further examine the impact
      of ADL and QOL related factors. The information will be helpful in improving the
      ADL and QOL of patients in the future.

PMID- 17554668
TI  - [Arduous navigation: the life story of a family raising a young child with Prader
      Willi syndrome].
AB  - The purpose of this narrative research was to explore the life experience of a
      family with a son suffering from congenital Prader-Willi syndrome (PWS).
      Difficulties associated with raising a PWS child led the mother to leave the
      family with her afflicted son. The author analyzed the story of this family and
      applied metaphors to describe the course of the family's life in terms of a
      "navigational map of life". This map included the six components of: 1. Leaving
      port (sailing toward an unknown future); 2. Facing a tsunami (undergoing a trial
      from God); 3. Striking a reef (a fragile boat in a vast ocean); 4. Isolated on an
      island (the interdependent relationship between mother and child); 5.
      Transformation (adjustment and starting over); and 6. Hoisting the sails (staying
      to the course of making dreams come true). In this study, the researcher served
      as the nu rse case manager and interacted with family members to provide health
      care, consultation and support as needed. The mother of this young PWS child has
      empowered herself, overcome her suffering and prepared herself well to face the
      challenges of the future.

PMID- 17554669
TI  - [Behavioral responses of an older woman receiving tocolysis after repeated failed
      pregnancies].
AB  - The purpose of this study was to explore the behavioral responses to tocolysis of
      an older woman who has experienced two failed pregnancies. As a participant
      observer the primary researcher simultaneously provided care and recorded the
      woman's verbal and nonverbal behaviors. After repeated data analysis, it was
      found that the woman's stress mainly resulted from her un certainty about a safe
      passage through pregnancy and about the health of her fetus. In her effort to
      ensure a successful pregnancy and good fetal health, she exhibited the following
      behaviors: worrying about the status of her pregnancy, adopting effective
      strategies to ensure the success of the tocolysis, complying with medical
      procedures and nursing instructions, establishing the time marks of the pregnancy
      for the purpose of self-encouragement, and attaching importance to oral intake
      for the sake of good fetal health. The article concludes that medical personnel
      should actively identify the needs of pregnant women and provide family-centered
      nursing care to diminish the impact of preterm premature rupture of membrane and
      maximize the positive results of tocolysis.

PMID- 17554670
TI  - [Improving recovery of body temperature after ablution in premature infants].
AB  - The purpose of this project was to improve the problem of decreased body
      temperature after ablution in premature infants, and increase the rate of
      recovery of body temperature. Before administration of this program, the rate of
      body temperature recovery was slow. The body temperatures of only 35% of
      premature infants' reached 36.5 degrees C at 30 minutes after bath, those of 43%
      did so at 60 minutes after bath, and those of 70 % did so at 120 minutes after
      bath. After a warmth maintenance nursing standard had been set, the bathing
      nursing standard corrected, standard interventions promoted and the system
      inspected, the percentage of body temperature recovery to 36.5 degrees C was
      raised from 35% to 74% at 30 minutes after bath and the body temperature became
      normal in all premature infants at 60 minutes after bath. This program not only
      solves the problem of low body temperature after ablution in premature infants,
      but also consolidates nursing staffs' knowledge and skills in maintaining body
      temperature in prematurity to promote the quality of premature care.

PMID- 17554671
TI  - [An exploration of the issues involved in family related research].
AB  - Nowadays, health care delivery systems are changing from hospital-based services
      to more family-oriented or community-oriented care. The development of family
      nursing and family research is the focus of more attention than ever before. A
      family is composed of individuals. It combines the characteristics of individuals
      and collective groups, which makes family research more complex than studies of
      individuals. Consequently, research into family-oriented areas presents
      additional challenges concerning conceptual methodological issues. This article
      focuses on the issues of family research concepts, research designs, definitions
      of family, sampling, study tools, and data analysis. In order to promote high
      quality family research outcomes, we propose below suggestions to serve as a
      guide to conducting family research: (1) identify the definition of family
      involved in a particular research question and choose a suitable methodology; (2)
      determine the number of family members and un its of analysis on theoretical
      bases; (3) select high-validity, high-reliability research tools in answering
      research questions; (4) analysis methods must match the concept of family and the
      characteristics of the units of analysis; (5) ethical issues must be respected in
      the recruitment of family members.

PMID- 17554672
TI  - [Perspectives on body: embodiment and body image].
AB  - "Body" is a basic concept of both the natural and human sciences. This extensive
      review of the literature explores the various philosophical approaches to the
      body, including empiricism, idealism, existentialism and phenomenology, as well
      as the relationship between body and mind. Embodiment and body image are the two
      main concepts of body addressed in this article. Merleau-Ponty's perspective on
      embodiment, an important new area of theory development, emphasizes that
      embodiment research must focus on life experiences, such as the study of body
      image. Using Schilder's framework of psychosocialology, this article provides a
      comprehensive understanding of the concept of body image and women's perspectives
      on the "body" in both Western culture and Eastern cultures. Body size and shape
      significantly influence the self-image of women. Body image is something that
      develops and changes throughout one's life span and is continually being
      constructed, destructed, and reconstructed. Personal body image has important
      psychological effects on the individual, especially women. This integrative
      review can make a significant contribution to knowledge in this area and,
      consequently, to related practice and research.

PMID- 17554673
TI  - [Family caregivers' adjustment to nursing home placement of older relatives].
AB  - The literature on the impact of nursing home placement of older parents on family
      caregivers is still incomplete. Family caregivers experience stress, shock,
      anxiety, fear, resistance, and guilt in the process of decision making. The
      literature has demonstrated that family caregivers continue to experience stress
      and problems after placing older relatives into a long term care facility.
      Cultural values impact on people's attitudes, values and expectations. Culture
      will therefore affect the care-giving experience. Relatively little information
      is available from Asian and multicultural societies. Identifying family caregiver
      experiences after nursing home placement can alert professionals to the need for
      family guidance prior to nursing home placement and assist in early
      identification of potential problems. This article reviews the literature and
      discusses the impact on family caregivers of making a decision for nursing home
      placement and dealing with the stress and challenges that persist after nursing
      home admission.

PMID- 17554674
TI  - [Nursing management of wound care pain].
AB  - Wound care is an important step in promoting wound healing, but it may cause
      wound care pain. This article aims to explore factors influencing wound care pain
      and the effectiveness of various interventions to alleviate it. Five major
      factors that influence wound care pain include inappropriate dressing change
      techniques, inflammation response, emotion, cognition, and social-cultural
      factors. Nurses should apply appropriate dressings and dressing change techniques
      to relieve wound care pain. Music therapy and aromatherapy can alleviate wound
      pain after dressing change. But distraction techniques should be used in
      conjunction with consideration of the needs of the individual subject.

PMID- 17554675
TI  - [Concept analysis of suffering].
AB  - Suffering is commonly encountered in nursing and is defined as an individual and
      subjective experience. It is a complex human response to which there are
      physical, psychological, social and spiritual aspects. Perception of suffering
      threatens self-integrity, and induces negative behaviors, such as personal
      changes in relation to value system, sense of reality, withdrawal, feelings of
      helplessness, and despair. A great deal of relevant literature explores the
      influence of suffering, but only a few articles analyze the concept of suffering.
      The purpose of this article, therefore, is to clarify the concept of suffering.
      In order to do this, we used the technique of concept analysis described by Chinn
      and Kramer (1995). It is hoped that the results of the study will enhance nurses'
      understanding of suffering and that its lessons may be adopted in clinical
      nursing.

PMID- 17554676
TI  - [The experience of nursing an AIDS patient whose secret was divulged to his
      family].
AB  - This article concerns an Acquired Immunodeficiency Syndrome (AIDS) patient who
      had contracted the disease through casual sex. The secret of the nature of his
      disease was accidentally divulged to his family and friends by his care provider.
      The patient was rejected by his family and friends. The nursing experience of
      caring for the physical and psychological symptoms of the patient was reported.
      The author collected data through observation, physical assessment, interview,
      and telephone communication from January 20, 2005 to January 31, 2005. Because of
      the disease and his alienation from family and friends, the patient felt a lack
      of trust for his care provider, as well as anxiety, fear, a sense of guilt, self
      recrimination, sadness and low self-esteem. The psychological symptoms were
      aggravated by the divulgence to family and friends of the fact that his disease
      was AIDS. The nursing problems were studied. The Watson theory of care was
      applied carefully. The patient was cared for with empathy and a positive
      attitude. A relationship of trust was established and the objective of quality
      care was accomplished. The nursing experience of caring for AIDS patients is
      unique. The privacy of the patient must be respected.

PMID- 17554677
TI  - [Hospice care for an AIDS patient and his family].
AB  - This article describes the emotional reactions, fear of contamination, and
      pressure to disclose HIV status of a patient who was recently diagnosed with
      AIDS, and his family. When the patient's condition deteriorated, his family and
      medical team faced ethical dilemmas about whether to disclose his condition to
      others, and the direction of his treatment. The authors and medical team applied
      the principles of hospice care. During each stage, the first author collected
      data by means of physical assessment, interview, participant observation, family
      meetings and team meetings, and provided a clear evaluation of the patient's
      clinical situation and disease prognosis. The first author applied the principles
      of hospice care and family-centered nursing care to enable the patient and his
      family to obtain physical comfort, to reduce the patient's fear of death, to
      enable him to enjoy the love of his whole family, and obtain his wife's
      forgiveness. After the patient's death, the first author called the family
      members and they came back to remember him in front of his room. The article
      shows that hospice care is crucial to AIDS patients and their families.

PMID- 17554678
TI  - Heart formation and left-right asymmetry in separated right and left embryos of a
      newt.
AB  - During vertebrate cardiac development, the heart tube formed by fusion of right
      and left presumptive cardiac mesoderms (PCMs) undergoes looping toward the right,
      resulting in an asymmetrical heart. Here, we examined the right and left PCMs
      with regard to heart-tube looping using right- and left-half newt embryos (Cynops
      pyrrhogaster ). In the half embryos, the rightward (normal) loop of the heart
      tube was formed from the left PCM, irrespective of the timing of its separation,
      while the leftward (reversed) loop of the heart tube was formed from the right
      PCM, separated by stage 18. In addition, the direction of the leftward loop was
      inverted to the rightward direction in right-half embryos bisected after stage
      18. Incision or resection of the embryonic caudal region implicated interactions
      between the right and left sides of this region as crucial for inverting the
      direction of the heart-tube loop from leftward to rightward in the right-half
      embryos. In situ hybridization of CyNodal (Cynops nodal-related gene) suggested
      that the inversion of heart looping in the right-half embryos has no association
      with the CyNodal expression pattern. Based on these findings, we propose a
      mechanism for the rightward looping underlying normal amphibian cardiac
      development.

PMID- 17554679
TI  - Analysis of a new allele of limb deformity (ld) reveals tissue- and age-specific
      transcriptional effects of the Ld Global Control Region.
AB  - The mouse limb deformity (ld) phenotype is characterized by developmental failure
      of distal limb structures often associated with renal anomalies. It is caused by
      loss of the BMP-antagonist Gremlin in the limb buds, either through mutation of
      Grem1, or by loss of a transcriptional global control region (GCR) located in the
      neighboring Fmn1 gene. In this report, we describe a new allele of ld due to
      complete deletion of Fmn1, including its GCR. Unlike many other ld strains, these
      mice are viable and fertile as homozygotes. As expected, this genomic deletion
      causes loss of Gremlin in the developing limb buds, but effects in other tissues
      are variable. Specifically, Grem1 expression is retained in the developing lung
      and kidney, whereas expression is lost from the corresponding adult tissues. In
      contrast, expression in the brain appears to be unaffected by loss of the GCR. To
      provide information about long-range transcriptional effects of this region,
      effects of the deletion on the transcription of neighboring genes were also
      investigated. This analysis revealed that alterations in neighboring genes do
      occur, but only in a limited fashion. These data indicate that the predominant
      effect of the Ld GCR is to activate the expression of Grem1 in the developing
      limb buds, although it may serve a minor role in long-range transcriptional
      effects that extend beyond Fmn1 and Grem1.

PMID- 17554680
TI  - Accumulation and dynamics of proteins of the MCM family during mouse oogenesis
      and the first embryonic cell cycle.
AB  - We describe the localization of three proteins of the minichromosome maintenance
      (MCM) family, Mcm2, -6 and -7 in mouse ovarian oocytes. We showed that Mcm
      proteins are stored in two forms: soluble and insoluble. Soluble Mcm2, -6 and -7
      were uniformly distributed in the nuclei of ovarian oocytes. Insoluble Mcm2 and
      Mcm7 (but not Mcm6) were detected in the nuclei of resting, growing and fully
      grown transcribing oocytes. In transcriptionally inactive fully-grown oocytes,
      Mcm2 underwent redistribution and Mcm7 disappeared. A similar effect was observed
      when transcription in growing oocytes was inhibited with alpha-amanitin. We
      postulate that in mouse oogenesis, the insoluble Mcm proteins are engaged in
      processes related to regulation of transcription and/or chromatin organization.
      In oocytes preparing for meiotic maturation, aggregates of the insoluble form of
      Mcm2 fragmented, dispersed and ultimately disappeared from the nuclei. Numerous
      Mcm2-positive deposits were observed in the cytoplasm of maturing oocytes. In the
      one-cell embryo, insoluble Mcm2 appeared in the G1 nucleus, persisted in the S
      phase and was undetectable in the G2 nucleus. Such behavior of Mcm2 supports its
      involvement in chromatin licensing in the first embryonic cell cycle.

PMID- 17554681
TI  - Cyclin B2/cyclin-dependent kinase1 dissociation precedes CDK1 Thr-161
      dephosphorylation upon M-phase promoting factor inactivation in Xenopus laevis
      cell-free extract.
AB  - Cyclin-dependent kinase 1 (CDK1) is the enzymatic subunit of M-phase Promoting
      Factor (MPF). It is positively regulated by phosphorylation on Thr-161 and
      association with a cyclin B molecule. The role of Thr-161 dephosphorylation upon
      MPF inactivation remains unclear; nevertheless, degradation of cyclin B is
      thought to be a direct cause of MPF inactivation. However, MPF inactivation
      actually precedes cyclin B degradation in Xenopus cell-free extracts. Here we
      study in details the temporal relationship between histone H1 kinase (reflecting
      MPF activity) inactivation, Thr-161 dephosphorylation, CDK1-cyclin B2
      dissociation and cyclin B2 proteolysis in such extracts. We show an asynchrony
      between inactivation of histone H1 kinase and degradation of cyclin B2. CDK1
      dephosphorylation on Thr 161 is an even later event than cyclin B2 degradation,
      reinforcing the hypothesis that cyclin B dissociation from CDK1 is the key event
      inactivating MPF. Cyclins synthesized along with MPF inactivation could deliver
      shortly living active MPF molecules, potentially increasing the asynchrony
      between histone H1 kinase inactivation and cyclin B2 degradation. We confirm this
      by showing that in the absence of protein synthesis, such a tendency is lower,
      but nevertheless, still detectable. Finally, to characterise better CDK1/cyclin B
      dissociation, we show that CDK1 begins to dissociate from cyclin B2 before the
      very beginning of cyclin B2 degradation and that the diminution in CDK1
      associated cyclin B2 is faster than the decline of its total pool. Thus, neither
      cyclin B2 degradation nor Thr-161 dephosphorylation participates directly in CDK1
      inactivation as measured by histone H1 kinase decline upon the exit from mitotic
      M-phase in Xenopus embryo extract.

PMID- 17554682
TI  - Serotonin involvement in the metamorphosis of the hydroid Eudendrium racemosum.
AB  - Hydroid planulae metamorphose in response to an inducing external stimulus,
      usually a bacterial cue. There is evidence that neurotransmitters participate in
      the signal transduction pathway of hydroid metamorphosis. Eudendrium racemosum is
      a colonial hydroid common in the Mediterranean Sea. It lacks the medusa stage and
      the planulae develop on female colonies during the fertile season. In this work,
      serotonin (5-HT) was localized in some planula ectodermal cells. Co-localization
      of serotonin and beta-tubulin suggested that 5-HT was present in sensory nervous
      cells and in different ectodermal cells. To investigate the role of
      neurotransmitters in metamorphosis, E. racemosum planulae were treated with
      serotonin and dopamine and with agonists and antagonists of the corresponding
      receptors. Serotonin and a serotonin receptor agonist induced metamorphosis,
      while a 5-HT receptor antagonist inhibited it. Dopamine and all dopaminergic
      drugs used did not show any significant effect on the onset of metamorphosis.
      Results from this work showed that 5-HT could stimulate metamorphosis in E.
      racemosum planulae in the presence of a natural inducer. A mechanism by which
      this neurotransmitter could act in this phase is proposed.

PMID- 17554683
TI  - Myoskeletin, a factor related to Myocardin, is expressed in somites and required
      for hypaxial muscle formation in Xenopus.
AB  - Myoskeletin was identified as a gene induced by activin in animal cap explants of
      Xenopus laevis. This gene encodes a protein related to the transcription factor
      Myocardin. Whereas Myocardin is expressed in the heart and is known to be
      involved in heart and smooth muscle formation, Myoskeletin is expressed in the
      somites and in hypaxial muscle precursors as they migrate away from the somites
      during tadpole stages. Myoskeletin is required for hypaxial muscle formation, as
      reduction of its expression through injection of an antisense morpholino
      oligonucleotide leads to suppression of hypaxial muscle formation. In
      overexpression experiments in animal caps, Myoskeletin is capable of inducing
      multiple genes including skeletal muscle, cardiac muscle and smooth muscle
      specific genes. We conclude that Myoskeletin is a somite and hypaxial muscle
      specific member of the Myocardin family that is required for hypaxial muscle
      formation.

PMID- 17554685
TI  - Pax7 identifies neural crest, chromatophore lineages and pigment stem cells
      during zebrafish development.
AB  - Using immunostaining during early zebrafish embryogenesis, we report that the
      cranial and trunk neural crest expresses the paired box protein Pax7, thus
      revealing a novel neural crest marker in zebrafish. In the head, we show that
      Pax7 is broadly expressed in the cranial crest cells, which indicates that
      duplication of the paralogous group Pax3/7 at the origin of vertebrates included
      the conserved expression of Pax7 in the head neural crest of all of the
      vertebrates species studied so far. In the trunk, Pax7 recognizes both
      premigratory and migratory neural crest cells. Notably, we observed the
      expression of Pax7 during the development of melanophore, xanthophore and
      iridophore precursor cells. In contrast to the case of melanocyte precursors in
      birds, Pax7 showed overlapping expression with early melanin pigment. Finally,
      during the larva to adult transition, we show that pigment stem cells
      recapitulate the expression of Pax7.

PMID- 17554684
TI  - The N-terminus zinc finger domain of Xenopus SIP1 is important for neural
      induction, but not for suppression of Xbra expression.
AB  - Smad-interacting protein-1 (SIP1), also known as deltaEF2, ZEB2 and zfhx1b, is
      essential for the formation of the neural tube and the somites. Overexpression of
      Xenopus SIP1 causes ectopic neural induction via inhibition of bone morphogenetic
      protein (BMP) signaling and inhibition of Xbra expression. Here, we report the
      functional analyses of 4 domain-deletion mutants of XSIP1. Deletion of the N
      terminus zinc finger domain suppressed neural induction and BMP inhibition, but
      these were not affected by deletion of the other domains (the Smad binding
      domain, the DNA-binding homeodomain together with the CtBP binding site and the C
      terminus zinc finger). Therefore SIP1 does not inhibit BMP signaling by binding
      to Smad proteins. In contrast, all of the deletion constructs inhibited Xbra
      expression. These results suggest that the N-terminus zinc finger domain of XSIP1
      has an important role in neural induction and that Xbra suppression occurs via a
      mechanism separate from the neural inducing activity.

PMID- 17554686
TI  - Isolation, genomic structure and developmental expression of Fgf8 in the short
      tailed fruit bat, Carollia perspicillata.
AB  - Fibroblast growth factor-8 (Fgf8) encodes a secreted protein which was initially
      identified as the factor responsible for androgen-dependant growth of mouse
      mammary carcinoma cells (Tanaka et al., 1992). Fgf8 has been subsequently
      implicated in the patterning and growth of the gastrulating embryo, paraxial
      mesoderm (somites), limbs, craniofacial tissues, central nervous system and other
      organ systems during the development of several vertebrate model animals.
      Consistent with these findings, Fgf8 is expressed in a complex and dynamic
      pattern during vertebrate embryogenesis. Here we report the isolation and
      characterization of a bat (Carollia perspicillata) Fgf8 orthologue. Compared with
      those of other model vertebrates, Carollia Fgf8 is conserved with respect to
      genomic structure, sequence and many domains of developmental expression pattern.
      Interestingly, the expression domain marking the apical ectodermal ridge of the
      developing limb shows a striking difference compared to that of mouse, consistent
      with evolutionary diversification of bat limb morphology.

PMID- 17554687
TI  - Expression and regulation of Xenopus CRMP-4 in the developing nervous system.
AB  - The collaspin response mediator proteins (CRMPs) are a family of cytosolic
      phosphoproteins which play a critical role in the establishment of neuronal
      polarity and growth cone guidance. Here, we describe the temporal and spatial
      expression of CRMP-4 during early Xenopus embryogenesis. CRMP-4 transcripts were
      first detected by whole mount in situ hybridization at the end of gastrulation in
      the prospective neuroectoderm. During open neural plate stages, CRMP-4 was
      expressed broadly throughout the anterior neural plate and in the three bilateral
      stripes of the posterior neural plate where primary neurons arise. The expression
      in the territories of primary neurogenesis prefigures that of the post-mitotic
      neuronal marker N-tubulin. At tadpole stages, expression was maintained
      throughout the central nervous system and in the retina of the eye. Consistent
      with the observed expression, CRMP-4 transcripts are positively regulated by X
      ngnr-1 and negatively by Notch signaling. The observed expression and regulation
      of CRMP-4 differ from that of the CRMP-2, which is induced by the events of
      neural induction.

PMID- 17554688
TI  - Characterization of novel genes expressed specifically in the sexual organs of
      the planarian Dugesia ryukyuensis.
AB  - The planarian Dugesia ryukyuensis reproduces both asexually (fissiparous) and
      sexually (oviparous) and can switch from the asexual mode to the sexual mode. By
      feeding with mature Bdellocephala brunnea oviparous worms, the fissiparous worms,
      which do not possess sexual organs, can be converted to fully sexualized worms in
      a process termed sexualization. As sexualization proceeds, the sexual organs are
      formed uniformly and five stages (stages 15) of the process have been identified
      histologically. In order to clarify the sexualization process, we attempted to
      isolate the genes expressed specifically at stage 5 by the differential display
      method. We isolated five genes expressed in the testis and two genes expressed in
      the yolk gland, which is an organ specific to sexualized worms. By BLAST search,
      one of the testis-specific genes was coded as testis-specific alpha-tubulin and
      two yolk gland-specific genes are similar to ribose-phosphate pyrophosphokinase I
      and F-box/SPRY-domain protein 1. Drs1, Drs2 and Drs3 were expressed in
      spermatocytes and spermatids from the early stage of spermatogenesis and Drs4 and
      Drs5 were expressed in spermatogonia, spermatocytes and spermatids. These genes
      are useful markers for elucidating the sexualization process.

PMID- 17554689
TI  - Chikungunya fever in travelers: clinical presentation and course.
AB  - BACKGROUND: An outbreak of chikungunya virus infection emerged in the southwest
      Indian Ocean islands in 2005, spread out to India, and resulted in an ongoing
      outbreak that has involved >1.5 million patients, including travelers who have
      visited these areas. METHODS: Our study investigated 69 travelers who developed
      signs and symptoms compatible with chikungunya fever after returning home from
      countries involved in the epidemic. Twenty cases of infection that were confirmed
      by serological analysis, polymerase chain reaction, and/or cell culture were
      investigated. RESULTS: All patients experienced flulike symptoms with fever and
      joint pain. No serious complications were observed, but 69% of the patients had
      persistent arthralgia for >2 months, and 13% had it for >6 months. Viral RNA
      could be detected in blood samples using reverse-transcriptase polymerase chain
      reaction in 4 of 4 patients who presented to a health care facility during their
      first week of illness, and the virus was successfully isolated from blood samples
      obtained from 2 of these patients. Chikungunya virus-specific immunoglobulin M
      and/or immunoglobulin G antibodies were detected in all patients. However,
      initial testing of serum samples yielded negative results for 3 of 5 patients
      during the first week. CONCLUSIONS: Chikungunya fever must be considered in
      travelers who develop fever and arthritis after traveling to areas affected by an
      ongoing epidemic. Related arthritis mainly affects smaller joints and often
      persists for extended periods. Serological testing may have negative results
      during the first week of the disease; diagnosis using polymerase chain reaction
      appears to be more reliable during this time. Travelers to areas of epidemicity
      should be informed of the risk of infection and of adequate preventive measures,
      such as protection against mosquitos.

PMID- 17554690
TI  - Acremonium vertebral osteomyelitis: molecular diagnosis and response to
      voriconazole.
AB  - We present a case of Acremonium vertebral osteomyelitis that relapsed despite
      surgical debridement and prolonged treatment with liposomal amphotericin B, but
      which responded to voriconazole therapy. The report highlights the role of
      molecular diagnosis of rare fungal osteomyelitis. The patient was successfully
      treated with voriconazole.

PMID- 17554691
TI  - Methotrexate treatment for type 1 (reversal) leprosy reactions.
AB  - Corticosteroids are the drugs of choice for treatment of type 1 leprosy
      reactions, but when these agents cannot be used because of their adverse effects,
      alternative treatments are needed. We report the first case, to our knowledge, of
      a type 1 leprosy reaction that was successfully treated with methotrexate in a
      patient intolerant to corticosteroids who had borderline lepromatous leprosy.

PMID- 17554693
TI  - Infection due to 3 avian influenza subtypes in United States veterinarians.
AB  - BACKGROUND: Pandemic influenza virus strains originate in avian species. We
      examined veterinarians in the United States for evidence of previous avian
      influenza virus infection. METHODS: We performed a controlled, cross-sectional
      seroprevalence study among 42 veterinarians and 66 healthy control subjects using
      serum samples collected from 2002 through 2004. Serum samples were tested using a
      microneutralization assay against 9 influenza A virus strains. RESULTS: Using
      multivariable logistic regression modeling, veterinarians exposed to birds
      demonstrated statistically significant elevated titers against the H5, H6, and H7
      avian influenza virus isolates, compared with control subjects. CONCLUSIONS:
      These data suggest that occupational exposure to avian species may increase
      veterinarians' risk of avian influenza virus infection. Veterinarians should be
      considered for priority access to vaccines and antiviral drugs in pandemic
      planning.

PMID- 17554694
TI  - Observation of practices at petting zoos and the potential impact on zoonotic
      disease transmission.
AB  - BACKGROUND: Although petting zoos are common at public events and allow the
      public to interact with animals, there has been minimal evaluation of practices
      at petting zoos. METHODS: Unannounced observation was performed at 36 petting
      zoos in Ontario, Canada. Observers recorded information, including physical
      layout, animal species, animal health, types of animal contact permitted, animal
      sources, hand hygiene facilities, signage, sale of food for human consumption,
      and hand hygiene compliance. RESULTS: The majority of petting zoos (24 [67%] of
      36 petting zoos) were part of temporary events, particularly agricultural fairs
      (21 [58%] of 36 petting zoos). A variety of animal species were present,
      including some animals that are considered to be at particularly high risk for
      disease transmission (neonatal calves and baby chicks). The following items that
      would come into contact with the mouths of infants and children were carried into
      the petting zoos: baby bottles (at 17 petting zoos; 50%), pacifiers (at 24
      petting zoos; 71%), spill-proofs cups (at 19 petting zoos; 56%), and infant toys
      (at 22 petting zoos; 65%). Hand hygiene facilities were provided at 34 (94%) of
      36 events, and hand hygiene compliance ranged from 0% through 77% (mean
      compliance [+/-SD], 30.9%+/-22.1%; median compliance, 26.5%). Predictors for
      increased hand hygiene compliance included the location of a hand hygiene station
      on an exit route, the presence of hand hygiene reminder signs, and the
      availability of running water. CONCLUSIONS: Numerous deficiencies were
      encountered. Better education of petting zoo operators and the general public is
      needed. Provision of hand hygiene stations with running water that are placed
      near exits is one effective way to encourage compliance.

PMID- 17554696
TI  - Intermittent preventive antimalarial treatment in infants.

PMID- 17554695
TI  - A randomized controlled trial of extended intermittent preventive antimalarial
      treatment in infants.
AB  - BACKGROUND: Intermittent preventive antimalarial treatment in infants (IPTi) with
      sulfadoxine-pyrimethamine reduces falciparum malaria and anemia but has not been
      evaluated in areas with intense perennial malaria transmission. It is unknown
      whether an additional treatment in the second year of life prolongs protection.
      METHODS: A randomized, double-blinded, placebo-controlled trial with
      administration of sulfadoxine-pyrimethamine therapy at 3, 9, and 15 months of age
      was conducted with 1070 children in an area in Ghana where malaria is
      holoendemic. Participants were monitored for 21 months after recruitment through
      active follow-up visits and passive case detection. The primary end point was
      malaria incidence, and additional outcome measures were anemia, outpatient
      visits, hospital admissions, and mortality. Stratified analyses for 6-month
      periods after each treatment were performed. RESULTS: Protective efficacy against
      malaria episodes was 20% (95% confidence interval [CI], 11%-29%). The frequency
      of malaria episodes was reduced after the first 2 sulfadoxine-pyrimethamine
      applications (protective efficacy, 23% [95% CI, 6%-36%] after the first dose and
      17% [95% CI, 1%-30%] after the second dose). After the third treatment at month
      15, however, no protection was achieved. Protection against the first or single
      anemia episode was only significant after the first IPTi dose (protective
      efficacy, 30%; 95% CI, 5%-49%). The number of anemia episodes increased after the
      last IPTi dose (protective efficacy, -24%; 95% CI, -50% to -2%). CONCLUSION: In
      an area of intense perennial malaria transmission, sulfadoxine-pyrimethamine
      based IPTi conferred considerably lower protection than reported in areas where
      the disease is moderately or seasonally endemic. Protective efficacy is age
      dependent, and extension of IPTi into the second year of life does not provide
      any benefit.

PMID- 17554697
TI  - Microbial colonization of the upper gastrointestinal tract in patients with
      Barrett's esophagus.
AB  - BACKGROUND: Barrett's esophagus (BE) is a complication of chronic
      gastroesophageal reflux disease, in which patients are at greatly increased risk
      of esophageal dysplasia and adenocarcinoma. Over the past 2 decades, there has
      been an increase in the incidence of both BE and adenocarcinoma; however, the
      involvement of microorganisms in BE is uncertain. The aim of this study was to
      characterize microbial communities in esophageal aspirate specimens and on distal
      esophageal mucosal samples from patients with BE. METHODS: Biopsy and aspirate
      specimens were obtained by endoscopic examination from 7 patients with BE and 7
      control subjects without BE. Samples were cultured under aerobic, anaerobic, and
      microaerophilic conditions for yeasts and bacteria, including Helicobacter
      pylori. Bacterial isolates were identified by 16S ribosomal RNA gene sequencing.
      Fluorescence microscopic examination was also used to determine the spatial
      localization of these organisms on mucosal surfaces. Significant colonization was
      detected in 6 patients with BE and in 4 control subjects. RESULTS: Overall, 46
      bacterial species belonging to 16 genera were detected, with 10 species being
      common in both groups. Both aspirate and biopsy samples from patients with BE
      contained complex populations of bacteria. Uniquely, high levels of Campylobacter
      species (Campylobacter concisus and Campylobacter rectus), which have been linked
      to enteritis, periodontal infections, and tumor formation in animals, were found
      in 4 (57%) of 7 patients with BE but in none of the control subjects. Microscopic
      examination revealed that bacteria on mucosal biofilms often occurred in
      microcolonies. CONCLUSIONS: The occurrence of nitrate-reducing Campylobacter
      species in patients with BE may suggest that there is a link in either the
      initiation, maintenance, or exacerbation of disease processes leading to
      adenocarcinoma formation.

PMID- 17554698
TI  - Prevalence, virulence profiles, and clinical significance of Shiga toxin-negative
      variants of enterohemorrhagic Escherichia coli O157 infection in humans.
AB  - BACKGROUND: Escherichia coli O157, of the H7 clone, exists in humans and in the
      environment as Shiga toxin (Stx)-positive and Stx-negative variants. Stx
      production by infecting organisms is considered to be a critical requirement for
      the development of hemolytic uremic syndrome (HUS), which occurs in approximately
      15% of E. coli O157-infected patients. It is unknown if loss of the stx gene
      during the early stage of an enterohemorrhagic E. coli infection prevents HUS, or
      if absence of the stx gene from E. coli O157 reduces or ablates virulence.
      METHODS: We determined the frequency of stx-positive and stx-negative E. coli
      O157 isolates in stool samples obtained from patients who experienced sporadic
      cases of diarrhea or HUS, as well as the frequency in samples obtained during
      outbreaks, and investigated the clinical course of the disease. RESULTS: Among E.
      coli O157 isolates obtained from samples related to sporadic cases of diarrhea,
      stx-negative strains accounted for 4%. The proportion of stx-negative strains was
      significantly higher among sorbitol-fermenting, nonmotile E. coli O157 isolates
      (12.7%) than among non-sorbitol-fermenting E. coli O157:H7 or nonmotile isolates
      (0.8%; P<.001). stx-Negative sorbitol-fermenting E. coli O157 isolates were also
      observed in samples related to 3 HUS outbreaks and 1 outbreak of diarrhea caused
      by sorbitol-fermenting, nonmotile enterohemorrhagic E. coli O157; additionally,
      they were the only pathogens that were isolated in 2 other outbreaks of diarrhea
      without HUS. CONCLUSIONS: Strains of stx-negative E. coli O157 isolated from
      stool samples of patients are either inherently stx-negative strains that cause
      mostly uncomplicated diarrhea, or strains that descended from enterohemorrhagic
      E. coli O157 by the loss of the stx gene during infection; the latter strains may
      still cause severe disease.

PMID- 17554699
TI  - Association of serotypes of Streptococcus pneumoniae with disease severity and
      outcome in adults: an international study.
AB  - BACKGROUND: The introduction of conjugate pneumococcal vaccination for children
      has reduced the burden of invasive disease due to pneumococcal conjugate vaccine
      (PCV) types (i.e., serotypes 9V, 14, 6B, 18C, 23F, 19F, and 4) in adults. As
      nonvaccine serotypes become predominant causes of invasive disease among adults,
      it is necessary to evaluate the disease severity and mortality associated with
      infection due to nonvaccine serotypes, compared with PCV serotypes, in adults.
      METHODS: The association of pneumococcal serotype and host-related variables with
      disease severity and mortality was statistically examined (with multivariable
      analysis) in 796 prospectively enrolled, hospitalized adult patients with
      bacteremia due to Streptococcus pneumoniae. RESULTS: In multivariate analyses of
      risk in patients with invasive pneumococcal disease, older age (age, > or = 65
      years; P = .004), underlying chronic disease (P = .025), immunosuppression (P =
      .035), and severity of disease (P < .001) were significantly associated with
      mortality; no association was found between nosocomial infection with invasive
      serotypes 1, 5, and 7 and mortality. The risk factors meningitis (P = .001),
      suppurative lung complications (P < or = .001), and preexisting lung disease (P =
      .051) were significantly associated with disease severity, independent of
      infecting serotype. No differences were seen in disease severity or associated
      mortality among patients infected with PCV serotypes, compared with patients
      infected with nonvaccine serotypes. CONCLUSIONS: Our data support the notion that
      host factors are more important than isolate serotype in determining the severity
      and outcome of invasive pneumococcal disease and that these outcomes are unlikely
      to change in association with nonvaccine serotype infection in the post-conjugate
      vaccine era.

PMID- 17554700
TI  - Capsular types and predicting patient outcomes in pneumococcal bacteremia.

PMID- 17554701
TI  - Postoperative central nervous system infection: incidence and associated factors
      in 2111 neurosurgical procedures.
AB  - BACKGROUND: Postoperative central nervous system infection (PCNSI) in patients
      undergoing neurosurgical procedures represents a serious problem that requires
      immediate attention. PCNSI most commonly manifests as meningitis, subdural
      empyema, and/or brain abscess. Recent studies (which have included a minimum of
      1000 operations) have reported that the incidence of PCNSI after neurosurgical
      procedures is 5%-7%, and many physicians believe that the true incidence is even
      higher. To address this issue, we examined the incidence of PCNSI in a sizeable
      patient population. METHODS: The medical records and postoperative courses for
      patients involved in 2111 neurosurgical procedures at our institution during 1991
      2005 were reviewed retrospectively to determine the incidence of PCNSI, the
      identity of offending organisms, and the factors associated with infection.
      RESULTS: The median age of patients at the time of surgery was 45 years. Of the
      1587 cranial operations, 14 (0.8%) were complicated by PCNSI, whereas none of the
      32 peripheral nerve operations resulted in PCNSI. The remaining 492 operative
      cases involved spinal surgery, of which 2 (0.4%) were complicated by PCNSI. The
      overall incidence of PCNSI was 0.8% (occurring after 16 of 2111 operations); the
      incidence of bacterial meningitis was 0.3% (occurring after 4 of 1587
      operations), and the incidence of brain abscess was 0.2% (occurring after 3 of
      1587 operations). The most common offending organism was Staphylococcus aureus (8
      cases; 50% of infections), followed by Propionibacterium acnes (4 cases; 25% of
      infections). Cerebrospinal fluid leakage, diabetes mellitus, and male sex were
      not associated with PCNSI (P>.05). CONCLUSIONS: In one of the largest
      neurosurgical studies to have investigated PCNSI, the incidence of infection
      after neurosurgical procedures was <1%--more than 6 times lower than that
      reported in recent series of comparable numerical size. Cerebrospinal fluid leak,
      diabetes mellitus, and male sex were not associated with an increased incidence
      of PCNSI. The results from this study indicate that the true incidence of PCNSI
      after neurosurgical procedures may be greatly overestimated in the literature and
      that, in surgical procedures associated with a high risk of infection,
      prophylaxis for S. aureus and/or P. acnes infection should be of primary concern.

PMID- 17554702
TI  - Association of the outcome of renal transplantation with antibody response to
      cytomegalovirus strain-specific glycoprotein H epitopes.
AB  - BACKGROUND: Cytomegalovirus (CMV) is the most important pathogen affecting the
      outcome of renal transplantation. The combination of CMV-seronegative transplant
      recipients with CMV-seropositive transplant donors places recipients at the
      highest risk of CMV disease. In cases of congenital CMV infection, existing
      immunity only partially protected mothers from reinfection with a different
      genotypic strain. The effect of differences in infected CMV strains between CMV
      seropositive transplant donors and CMV seropositive transplant recipients on the
      outcome of transplantation remains unclear. METHODS: In this prospective
      multicenter study, the presence of antibodies against strain-specific
      glycoprotein H epitopes in 84 CMV-seropositive transplant donor/CMV-seropositive
      transplant recipient renal transplantation cases were determined, and their
      relationships to acute transplant rejection, CMV infection, degree of
      antigenemia, and CMV disease were evaluated. RESULTS: Among the 84
      donor/recipient pairs, 45 and 32 had matched and mismatched strain-specific
      glycoprotein H antibodies, respectively. Acute transplant rejection in the
      mismatched group was more frequent than it was in the matched group (63% vs. 22%;
      P=.005). CMV disease was also more frequently observed in the mismatched group
      (28% vs. 9%; P=.026). The mismatched group had a higher level of antigenemia
      (P=.019). CONCLUSIONS: Our results illustrate more adverse events in the cases
      with a CMV-seropositive transplant donor and a CMV-seropositive transplant
      recipient in which the glycoprotein H antibodies are mismatched, suggesting that
      reinfection with a different CMV strain results in more complications.

PMID- 17554703
TI  - Dry reagent-based polymerase chain reaction compared with other laboratory
      methods available for the diagnosis of Buruli ulcer disease.
AB  - BACKGROUND: Because of the multifaceted clinical presentation of Buruli ulcer
      disease, misclassification of clinically diagnosed cases may occur frequently.
      Laboratory tests for the confirmation of suspected cases include microscopic
      examination, culture, polymerase chain reaction (PCR), and histopathologic
      examination. However, microscopic examination, the only test usually available in
      areas of endemicity, has a low sensitivity. METHODS: To make a highly sensitive
      diagnostic method locally available, dry reagent-based PCR (DRB-PCR), which is
      well adapted to tropical conditions, was pilot-tested in Ghana. Subsequently, the
      assay was used for the routine diagnosis of Buruli ulcer disease over a period of
      2 years. The method was compared with other diagnostic tests to evaluate its
      performance under field conditions. RESULTS: The interassay agreement rate
      between DRB-PCR and standard PCR was 91.7% for swab specimens and 95% for tissue
      specimens. Among all of the locally available tests, DRB-PCR revealed the highest
      overall positivity ratio. Sixty percent of patients with clinical diagnoses of
      Buruli ulcer disease had the diagnoses confirmed by DRB-PCR of swab or tissue
      specimens, compared with 30%-40% of patients who had diagnoses confirmed by
      microscopic examination of swab or tissue specimens. The positivity ratio of DRB
      PCR varied considerably when analyzed per treatment center. Standardization of
      specimen collection resulted in a 30% increase in the positivity ratio of the
      assay, compared with that in the pilot-testing phase. CONCLUSIONS: DRB-PCR is a
      reliable tool for the diagnosis of Buruli ulcer disease. However, PCR assays are
      suitable for detection only during early stages of the disease, when samples
      still contain bacilli. The quality of clinical diagnosis and the quality of
      diagnostic specimens strongly influence the positivity ratio.

PMID- 17554704
TI  - Fungal burden, early fungicidal activity, and outcome in cryptococcal meningitis
      in antiretroviral-naive or antiretroviral-experienced patients treated with
      amphotericin B or fluconazole.
AB  - In a prospective observational study of 54 patients with human immunodeficiency
      virus-associated cryptococcal meningitis, the early fungicidal activity of
      amphotericin B (1 mg/kg/day) was significantly greater than that of fluconazole
      (400 mg/day). Compared with antiretroviral therapy-naive patients, patients
      developing cryptococcal meningitis while already receiving antiretroviral therapy
      had lower baseline fungal burdens and a longer median duration of survival, but
      there were no differences observed in fungal clearance, cerebrospinal fluid
      proinflammatory cytokines, or 10-week mortality.

PMID- 17554705
TI  - Management of cryptococcal meningitis in AIDS: the need for specific studies in
      developing countries.

PMID- 17554706
TI  - Impact of copper and silver ionization on fungal colonization of the water supply
      in health care centers: implications for immunocompromised patients.
AB  - Copper and silver ionization is a well-recognized disinfection method to control
      Legionella species in water distribution systems in hospitals. These systems may
      also serve as a potential indoor reservoir for fungi. The prevalence of fungi was
      significantly lower in ionized than in nonionized water samples from health care
      facilities. The clinical consequences of this finding require further
      investigation.

PMID- 17554707
TI  - A patient with a painless neck swelling.

PMID- 17554708
TI  - 16S ribosomal RNA methylation: emerging resistance mechanism against
      aminoglycosides.
AB  - Methylation of 16S ribosomal RNA (rRNA) has recently emerged as a new mechanism
      of resistance against aminoglycosides among gram-negative pathogens belonging to
      the family Enterobacteriaceae and glucose-nonfermentative microbes, including
      Pseudomonas aeruginosa and Acinetobacter species. This event is mediated by a
      newly recognized group of 16S rRNA methylases, which share modest similarity to
      those produced by aminoglycoside-producing actinomycetes. Their presence confers
      a high level of resistance to all parenterally administered aminoglycosides that
      are currently in clinical use. The responsible genes are mostly located on
      transposons within transferable plasmids, which provides them with the potential
      to spread horizontally and may in part explain the already worldwide distribution
      of this novel resistance mechanism. Some of these organisms have been found to
      coproduce extended-spectrum beta-lactamases or metallo-beta-lactamases,
      contributing to their multidrug-resistant phenotypes. A 2-tiered approach,
      consisting of disk diffusion tests followed by confirmation with polymerase chain
      reaction, is recommended for detection of 16S rRNA methylase-mediated resistance.

PMID- 17554709
TI  - The discovery and characterization of Mimivirus, the largest known virus and
      putative pneumonia agent.
AB  - During recent years, the usefulness of amoebal co-cultures as an alternative
      means of isolating and cultivating fastidious microorganisms has been
      increasingly recognized. While characterizing a collection of bacteria that had
      been isolated using this approach, we encountered an organism that, on
      preliminary analysis, appeared to be a gram-positive coccus. However, additional
      examination revealed that it was not a bacterium but rather, surprisingly, a
      virus. The dimensions of the virus particle (diameter, 0.8 microm) and its genome
      size (1.2 Mb) are far more akin to those of bacteria than to those of previously
      recognized viruses. These characteristics, together with such features as the
      breadth and complexity of its gene content, challenge the current definition of a
      "virus." Furthermore, the virus, now named "Mimivirus," has been implicated as an
      agent of pneumonia in humans and, thus, should be considered a putative emerging
      pathogen.

PMID- 17554710
TI  - HIV infection is associated with an increased risk for lung cancer, independent
      of smoking.
AB  - BACKGROUND: Human immunodeficiency virus (HIV)-infected persons have an elevated
      risk for lung cancer, but whether the increase reflects solely their heavy
      tobacco use remains an open question. METHODS: The Acquired Immunodeficiency
      Syndrome (AIDS) Link to the Intravenous Experience Study has prospectively
      observed a cohort of injection drug users in Baltimore, Maryland, since 1988,
      using biannual collection of clinical, laboratory, and behavioral data. Lung
      cancer deaths were identified through linkage with the National Death Index. Cox
      proportional hazards regression was used to examine the effect of HIV infection
      on lung cancer risk, controlling for smoking status, drug use, and clinical
      variables. RESULTS: Among 2086 AIDS Link to the Intravenous Experience Study
      participants observed for 19,835 person-years, 27 lung cancer deaths were
      identified; 14 of the deaths were among HIV-infected persons. All but 1 (96%) of
      the patients with lung cancer were smokers, smoking a mean of 1.2 packs per day.
      Lung cancer mortality increased during the highly active antiretroviral therapy
      era, compared with the pre-highly active antiretroviral therapy period (mortality
      rate ratio, 4.7; 95% confidence interval, 1.7-16). After adjusting for age, sex,
      smoking status, and calendar period, HIV infection was associated with increased
      lung cancer risk (hazard ratio, 3.6; 95% confidence interval, 1.6-7.9).
      Preexisting lung disease, particularly noninfectious diseases and asthma,
      displayed trends for increased lung cancer risk. Illicit drug use was not
      associated with increased lung cancer risk. Among HIV-infected persons, smoking
      remained the major risk factor; CD4 cell count and HIV load were not strongly
      associated with increased lung cancer risk, and trends for increased risk with
      use of highly active antiretroviral therapy were not significant. CONCLUSIONS:
      HIV infection is associated with significantly increased risk for developing lung
      cancer, independent of smoking status.

PMID- 17554711
TI  - Factors associated with the incidence of type 2 diabetes mellitus in HIV-infected
      participants in the Swiss HIV Cohort Study.
AB  - BACKGROUND: Human immunodeficiency virus (HIV)-infected persons may be at
      increased risk for developing type 2 diabetes mellitus because of viral
      coinfection and adverse effects of treatment. METHODS: We studied associations of
      new-onset diabetes mellitus with hepatitis B virus and hepatitis C virus
      coinfections and antiretroviral therapy in participants in the Swiss HIV Cohort
      Study, using Poisson regression. RESULTS: A total of 123 of 6513 persons
      experienced diabetes mellitus during 27,798 person-years of follow-up (PYFU),
      resulting in an incidence of 4.4 cases per 1000 PYFU (95% confidence interval
      [CI], 3.7-5.3 cases per 1000 PYFU). An increased incidence rate ratio (IRR) was
      found for male subjects (IRR, 2.5; 95% CI, 1.5-4.2), older age (IRR for subjects
      >60 years old, 4.3; 95% CI, 2.3-8.2), black (IRR, 2.1; 95% CI, 1.1-4.0) and Asian
      (IRR, 4.9; 95% CI, 2.2-10.9) ethnicity, Centers for Disease Control and
      Prevention disease stage C (IRR, 1.6; 95% CI, 1.04-2.4), and obesity (IRR, 4.7;
      95% CI, 3.1-7.0), but results for hepatitis C virus infection or active hepatitis
      B virus infection were inconclusive. Strong associations were found for current
      treatment with nucleoside reverse-transcriptase inhibitors (IRR, 2.22; 95% CI,
      1.11-4.45), nucleoside reverse-transcriptase inhibitors plus protease inhibitors
      (IRR, 2.48; 95% CI, 1.42-4.31), and nucleoside reverse-transcriptase inhibitors
      plus protease inhibitors and nonnucleoside reverse-transcriptase inhibitors (IRR,
      3.25; 95% CI, 1.59-6.67) but were not found for treatment with nucleoside reverse
      transcriptase inhibitors plus nonnucleoside reverse-transcriptase inhibitors
      (IRR, 1.47; 95% CI, 0.77-2.82). CONCLUSIONS: In addition to traditional risk
      factors, current treatment with protease inhibitor- and nucleoside reverse
      transcriptase inhibitor-containing regimens was associated with the risk of
      developing type 2 diabetes mellitus. Our study did not find a significant
      association between viral hepatitis infection and risk of incident diabetes.

PMID- 17554712
TI  - Effects of potent antiretroviral therapy on free testosterone levels and fat-free
      mass in men in a prospective, randomized trial: A5005s, a substudy of AIDS
      Clinical Trials Group Study 384.
AB  - BACKGROUND: Low testosterone levels are commonly reported in patients with
      advanced human immunodeficiency virus disease. The effects of initiation of
      different antiretroviral regimens on testosterone levels and changes in fat-free
      mass have not been reported. METHODS: Antiretroviral-naive men (n=213) were
      randomized to receive nelfinavir, efavirenz, or both plus either zidovudine and
      lamivudine or stavudine and didanosine. Patients underwent measurements of
      metabolic parameters, including determination of free testosterone level by
      equilibrium dialysis and bioelectrical impedance analysis, over a 64-week period.
      RESULTS: At baseline, the median free testosterone level was 92 pg/mL; the level
      was subnormal (i.e., <50 pg/mL) in 6%. Lower CD4 cell count at the time of study
      entry, higher weight, and greater age were independently associated with lower
      baseline free testosterone level. At week 64, the median free testosterone level
      increased more in zidovudine-lamivudine recipients (48 of whom had paired values
      available; change, +31 pg/mL) than in stavudine-didanosine recipients (57 of whom
      had paired values; change, +3 pg/mL; P=.001, by Wilcoxon rank sum test), and it
      increased more in efavirenz recipients (37 of whom had paired values; change, +30
      pg/mL) than in nelfinavir recipients (28 of whom had paired values; change, -3
      pg/mL; P=.05). The median fat-free mass for the entire group increased by 1.2 kg
      at week 64 (change, +2.0%; P<.001); the increase was greater in the zidovudine
      lamivudine group (n=70; change, +1.8 kg) than in the stavudine-didanosine group
      (n=79; change, +0.5 kg; P=.04), and the increase was also greater for efavirenz
      recipients (n=53; change, +2.1 kg) than among nelfinavir recipients (n=47;
      change, +0.4 kg; P=.003). White race, lower CD4 cell count at study entry,
      assignment to the efavirenz treatment arm, and assignment to the zidovudine
      lamivudine treatment arm independently predicted greater absolute change in fat
      free mass at week 64. CONCLUSIONS: Subnormal free testosterone levels occurred
      infrequently among these antiretroviral-naive men. Free testosterone and fat-free
      mass levels increased after initiation of antiretroviral therapy, with greater
      increases at 64 weeks among zidovudine-lamivudine recipients than among stavudine
      didanosine recipients and among efavirenz recipients than among nelfinavir
      recipients.

PMID- 17554713
TI  - Failure to establish HIV care: characterizing the "no show" phenomenon.
AB  - It is estimated that up to one-third of persons with known human immunodeficiency
      virus (HIV) infection in the United States are not engaged in care. We evaluated
      factors associated with patients' failure to establish outpatient HIV care at our
      clinic and found that females, racial minorities, and patients lacking private
      health insurance were more likely to be "no shows." At the clinic level, longer
      waiting time from the call to schedule a new patient visit to the appointment
      date was associated with failure to establish care. Because increased numbers of
      patients will be in need of outpatient HIV care as a result of recent Centers for
      Disease Control and Prevention guidelines advocating routine HIV testing, it is
      imperative that strategies to improve access are developed to overcome the "no
      show" phenomenon.

PMID- 17554715
TI  - Ethical considerations regarding the administration of oseltamivir for infection
      control indications.

PMID- 17554716
TI  - Fluoroquinolones should not be the first-line antibiotics to treat community
      acquired pneumonia in areas of tuberculosis endemicity.

PMID- 17554718
TI  - Point-of-use water filtration complements systemic treatment to reduce health
      care-associated Legionnaires disease.

PMID- 17554719
TI  - Diffuse cutaneous hyperpigmentation due to tigecycline or polymyxin B.

PMID- 17554721
TI  - Diagnosing catheter-related bloodstream infection without catheter removal? Not
      so fast!

PMID- 17554722
TI  - Refrain from telling bad news: patients with leishmaniasis can have false
      positive HIV test results.

PMID- 17554723
TI  - In vitro activity of colistin against multidrug-resistant gram-negative bacteria
      isolated at a major army hospital during the military campaigns in Iraq and
      Afghanistan.

PMID- 17554725
TI  - [Towards evidence-based nephrology: the seeming paradox of "out-of-line"
      guidelines].

PMID- 17554726
TI  - [Is it time to abandon renal biopsy?].

PMID- 17554724
TI  - [The peritoneum: a dilemma for the nephrologist].

PMID- 17554727
TI  - [Renal replacement therapy for acute renal failure in intensive care: is more
      better?].

PMID- 17554728
TI  - [Lupus nephritis: a matter of Toll...erance].

PMID- 17554729
TI  - [Is the peritoneal equilibration test clinically useful?].

PMID- 17554730
TI  - [A brief "update" on renal effects of caffeine].
AB  - Caffeine is one of the most frequently consumed substances worldwide. It is
      present in some common beverages such as tea and coffee and in a variety of
      drugs, particularly analgesics. Its main mechanisms of action include inhibition
      of phosphodiesterase enzyme and adenosine receptors; its effects involve the
      whole body. In recent years there has been a debate in the scientific literature
      over the relationship between caffeine and the kidney and its possible toxicity.
      Several experimental studies have demonstrated that caffeine may exacerbate some
      pathological conditions such as polycystic disease and proteinuria, while others
      have underlined its protective effects in specific situations. While awaiting
      new, in-depth studies that will help to solve the debate, we can conclude that
      there is currently no evidence contraindicating the consumption of moderate
      quantities of caffeine by healthy subjects or kidney patients.

PMID- 17554731
TI  - [Antiphospholipid syndrome and preeclampsia].
AB  - Preeclampsia is defined as gestational hypertension plus proteinuria (>= 300
      mg/day). It is a common disorder during pregnancy, accounting for about 20% of
      fetal mortality occurring after the 20th week of gestation. Preeclampsia is
      considered severe when it involves severe gestational hypertension and/or
      proteinuria >= 5 g/day, or when it is associated with pulmonary edema, oliguria,
      thrombocytopenia, elevation of liver enzymes, or involvement of the central
      nervous system. Antiphospholipid antibody syndrome (APS) is at present considered
      one of the predisposing conditions for the occurrence of severe preeclampsia.
      This review provides an update of the best available treatments to prevent the
      evolution of APS towards severe preeclampsia. The proposed pharmacological
      approach, based on the use of low-dose salicylate alone or combined with low
      molecular-weight heparin, is titrated against different subsets of clinical and
      laboratory data. Thorough treatment and close surveillance of patients suffering
      from APS during pregnancy requires the expertise of a joint team consisting of
      gynecologists, neonatal doctors, nephrologists, anesthesiologists, and
      rheumatologists.

PMID- 17554732
TI  - [Prevention of HCV infection in the hemodialysis setting].
AB  - The discovery of hepatitis C viruses in the 1990s started a new era in
      hemodialysis. Hepatotropic RNA viruses are able to infect the immune cell
      populations of the host and show high viral persistence and chronicity rates.
      Although, like the HIV viruses, they can change inside the host, they are less
      resistant than hepatitis B viruses both to environmental conditions and common
      disinfection tools. The clinically subtle course of chronic and acute infections
      has pivotal importance in the spread of HCV and can explain its prevalence rates
      of 2-3% in the general population and about 9% in hemodialysis patients. Among
      the risk factors for transmission, the nosocomial risk is of primary importance
      in the hemodialysis setting but it is present in every health-care environment.
      Though low, also the occupational risk is important, particularly for nurses, in
      whom accidental pricks are responsible for a mean incidence of HCV infection of
      1.8%. In the dialysis setting both these risk factors are essentially imputable
      to sanitary malpractice. In the last 30 years, the most important agencies for
      the prevention of infection have developed a set of "special" precautions for
      particular settings such as hemodialysis. In this review we report and recommend
      these precautions because their regular adoption is fundamental and a sufficient
      requisite to prevent the spread of hematogenous infections, including HCV.

PMID- 17554733
TI  - [Chemokines: possible therapeutic targets and useful clinical parameters in renal
      transplantation].
AB  - Chemokines are a family of small, structurally related cytokines that regulate
      trafficking of different subsets of leukocytes, thus critically regulating
      inflammation. The chemokine system influences allograft biology at 3 main levels:
      1) the process of ischemia-reperfusion injury, 2) the induction of transplant
      tolerance, and 3) the pathogenesis of acute rejection and chronic allograft
      nephropathy. Accordingly, following ischemia/reperfusion in a rat model, CXCR2
      produced at the graft level attracts and activates granulocytes, which in turn
      promotes graft damage. Moreover, in some experimental models CCR4 recruits T
      regulatory cells and mediates transplant tolerance. Furthermore, the discovery of
      the involvement of CXCR3 in the induction of the alloresponse to transplant
      suggests that this chemokine receptor might represent an important target for
      treatment of both acute rejection and chronic allograft nephropathy. Indeed,
      CXCR3 ligands play a pivotal role in the initiation and amplification of host
      alloresponses and also alter vascular cell functions, which explains their
      critical role not only in the development of acute rejection, but also in the
      pathogenesis of chronic allograft nephropathy, where both immune- and nonimmune-
      mediated mechanisms are involved. Finally, we have recently demonstrated that the
      pretransplant serum level of the CXCR3 ligand IP-10/CXCL10 is a clinically useful
      parameter for the identification of subjects with a high risk of acute rejection,
      chronic allograft nephropathy, and graft failure. This simple test could
      contribute to the prevention of acute rejections and the individualization of
      immunosuppressive therapies.

PMID- 17554734
TI  - [DOPPS estimate of guideline impact on survival in hemodialysis in Italy].
AB  - Knowing the relative risk (RR) of mortality associated with being outside the
      guideline targets and the percentage of patients in this situation, it is
      possible to estimate the number of patient life years that could be gained from
      adhering to guideline recommendations. We used a prevalent cross-sectional sample
      of 576 Italian patients from the Dialysis Outcomes and Practices Patterns Study
      (DOPPS) phase II (2002-2004) to determine the percentage of patients who failed
      to meet the Italian Society of Nephrology's targets for dialysis dose (spKt/V >=
      1.3), anemia management (hemoglobin >= 11 g/dL), and mineral metabolism (serum
      calcium and phosphorus: <= 2.6 and <= 1.8 mmol/L, respectively), and the National
      Kidney Foundation's Kidney Disease Outcomes Quality Initiative (K/DOQI) targets
      for nutritional status (serum albumin >= 4 g/dL) and vascular access (facility
      catheter use <= 10%). We used a larger random sample of DOPPS patients to
      establish the adjusted RRs of mortality associated with the 6 examined targets.
      The percentage of patients outside the targets and the adjusted RRs were 34% and
      1.12 for dialysis dose, 37.7% and 1.20 for anemia management, 40.8% and 1.14 for
      phosphorus, 14.4% and 1.22 for calcium, 62.5% and 1.46 for albumin, and 40.1% and
      1.20 for facility catheter use. The adjusted sum of life years potentially gained
      by complete adherence to all 6 guidelines was 25,156 over a period of 5 years
      (2006-2010); a more conservative estimate, modeling life years potentially gained
      by bringing half of all patients outside targets within them, was 13,382. In
      conclusion, this analysis suggests opportunities to improve hemodialysis patient
      care in Italy. The magnitude of potential savings in life years should encourage
      greater adherence to guidelines and practices that are significantly associated
      with better survival.

PMID- 17554735
TI  - [Avascular jaw osteonecrosis in a hemodialysis patient treated with
      bisphosphonates].
AB  - Bisphosphonates are molecules derived from pyrophosphates,but, unlike
      pyrophosphates, they are resistant to enzymatic hydrolysis. Bisphosphonates are
      used in the treatment of Paget's disease, cancer-related osteolysis, myeloma,
      primary hyperparathyroidism, and osteoporosis. In dialysis patients
      bisphosphonates may be used to reduce bone pain due to renal osteodystrophy. We
      describe the case of a 60-year-old woman with a history of breast cancer who had
      been on dialysis for 8 years. She had been receiving clodronic acid at 100 mg per
      week intravenously for the last 2 years. A year ago, the patient underwent
      surgical extraction of the lower right second molar. Her jaw pain increased in
      the following days. An orthopanthograph and a CT scan of the head showed
      osteolysis, and a surgical osteotomy was performed. Histological examination led
      to a diagnosis of avascular osteonecrosis of the jaw. Avascular osteonecrosis is
      typically described in the jaw. In this case, prolonged bisphosphonate treatment
      may have worsened the osteonecrosis.

PMID- 17554736
TI  - [1966: an automatic peritoneal dialysis machine. A personal experience].
AB  - In 1966 a self-made peritoneal dialysis machine according to Boen's model was
      built at the Nephrology Unit of the University of Turin (Italy) to facilitate the
      conduction of "rapid-exchange" peritoneal dialysis. Three timers controlled the
      dialysate inflow, dwell and outflow phases. Inflow and outflow times were reduced
      by means of wide dialysate lines and negative pressure in the drainage reservoir.
      A mechanical recorder registered the outflow curves. With rapid-exchange
      peritoneal dialysis, urea clearance increased from 18 to 34 mL/min, thereby
      improving the treatment of both acute and chronic renal failure patients.

PMID- 17554737
TI  - [Advance directives for health care: law initiatives in the current legislature].

PMID- 17554738
TI  - [Treatment of uremia in frail elderly patients: the issue of prolonged
      conservative management].
AB  - The chronic use of renal replacement therapy in frail elderly patients sometimes
      provides no tangible benefits and may even have a negative fallout on their
      quality of life, making prolonged conservative management a reasonable option.
      However, this is mostly a feeling, since very few papers have addressed this
      issue and there is no evidence-based medicine related to it. On the other hand,
      ethical issues are extraordinarily relevant and in this clinical setting extend
      beyond topics such as end-of-life care and advance care planning. It is evident
      that clinical decision-making in frail elderly patients with endstage renal
      disease may be very difficult and needs to be supported by ad hoc clinical
      trials. In the meantime, the ethical issues must be discussed in society.

PMID- 17554739
TI  - [Interpersonal relationship with the nephropathic patient].

PMID- 17554741
TI  - [Adjustment, quality of life, family support and social support of the dialysis
      patient].

PMID- 17554743
TI  - High-throughput identification of substrate specificity for protein kinase by
      using an improved one-bead-one-compound library approach.

PMID- 17554744
TI  - Supramolecular helical structure of the stereocomplex composed of complementary
      isotactic and syndiotactic poly(methyl methacrylate)s as revealed by atomic force
      microscopy.

PMID- 17554745
TI  - Real-time control of a catalytic solid in a fixed-bed reactor based on in situ
      spectroscopy.

PMID- 17554746
TI  - Rapid and highly selective copper-free sonogashira coupling in high-pressure,
      high-temperature water in a microfluidic system.

PMID- 17554747
TI  - Efficient CuO-nanoparticle-catalyzed C-S cross-coupling of thiols with
      iodobenzene.

PMID- 17554748
TI  - Hydrocarbon-stapled helices: a novel approach for blocking protein-protein
      interactions.

PMID- 17554750
TI  - Habitual hot-spring bathing by a group of Japanese macaques (Macaca fuscata) in
      their natural habitat.
AB  - Japanese macaques (Macaca fuscata) in a free-ranging group in Jigokudani valley,
      Nagano prefecture, are known to bathe in a hot spring. We used scan sampling in a
      study aimed at elucidating the causal factors and possible social transmission of
      this behavior. From 1980-2003, 31% of a total 114 females in the group habitually
      bathed in the hot spring. The habit was more widespread in dominant matrilines
      than in subordinate matrilines. Infants whose mothers bathed were more likely to
      bathe than infants of mothers who did not bathe. The number of monkeys bathing
      was clearly influenced by ambient air temperature. More monkeys bathed in the hot
      spring in winter than in summer. The results support the thermoregulation
      hypothesis of hot-spring bathing. Bathing behavior varies among age and sex
      categories of monkeys, with adult females and juveniles bathing more often than
      adult males and subadults. We compared hot-spring bathing with other
      thermoregulatory behaviors in various primate populations.

PMID- 17554749
TI  - Phylogenetic relationships of Danio within the order Cypriniformes: a framework
      for comparative and evolutionary studies of a model species.
AB  - The evolutionary relationships of species of Danio and the monophyly and
      phylogenetic placement of the genus within the family Cyprinidae and subfamily
      Rasborinae provide fundamentally important phyloinformatics necessary for direct
      evaluations of an array of pertinent questions in modern comparative biology.
      Although the genus Danio is not one of the most diverse within the family, Danio
      rerio is one of the most important model species in biology. Many investigations
      have used this species or presumed close relatives to address specific questions
      that have lasting impact on the hypothesis and theory of development in
      vertebrates. Largely lacking from this approach has been a holistic picture of
      the exact phylogenetic or evolutionary relationships of this species and its
      close relatives. One thing that has been learned over the previous century is
      that many organismal attributes (e.g., developmental pathways, ecologies,
      behaviors, speciation) are historically constrained and their origins and
      functions are best explained via a phylogenetic approach. Herein, we provide a
      molecular evaluation of the phylogenetic placement of the model species Danio
      rerio within the genus Danio and among hypothesized closely related species and
      genera. Our analysis is derived from data using two nuclear genes (RAG1,
      rhodopsin) and five mitochondrial genes (ND4, ND4L, ND5, COI, cyt b) evaluated
      using parsimony, maximum likelihood, and Bayesian analyses. The family Cyprinidae
      is resolved as monophyletic but the subfamily Rasborinae (priority over
      Danioinae) is an unnatural assemblage. Danio is identified as a monophyletic
      group sister to a clade inclusive of the genera Chela, Microrasbora, Devario, and
      Inlecypris, not Devario nor Esomus as hypothesized in previous studies. Danio
      rerio is sister to D. kyathit among the species of Danio evaluated in this
      analysis. Microrasbora and Rasbora are non-monophyletic assemblages; however,
      Boraras is monophyletic.

PMID- 17554751
TI  - The effect of male tenure and female mate choice on paternity in free-ranging
      Japanese macaques.
AB  - In this study, the paternity of all the infants born in 2002 and 2003 in a free
      ranging Japanese macaque (Macaca fuscata) group at Arashiyama in Kyoto, Japan,
      was analyzed in relation to males' age, dominance rank, and tenure and females'
      mate choice. The fathers of 20 out of 23 infants were determined by DNA analyses.
      Central adult (high-ranking) males sired two infants, whereas peripheral adult
      (low-ranking) males sired 14 infants. Young males sired only one infant. Among
      adult males, tenure was the most dominant factor that negatively affected male
      reproductive success. The mating behavior of females who gave birth was also
      analyzed. The number of male copulations in the peri-fertilization period was
      positively correlated with the number of infants that they sired. Females
      copulated with central males with a long tenure only when fertilization was
      unlikely or impossible. The females probably avoided insemination by males with a
      long tenure and selected males with a shorter tenure as their mating partners
      during the ovulation period.

PMID- 17554752
TI  - Analysis of peptide design in four-, five-, and six-helix bundle template
      assembled synthetic protein molecules.
AB  - Four-, five-, and six-helix bundle template assembled synthetic proteins (TASPs)
      have been synthesized using disulfide bonds between cavitand templates and
      peptides, and characterized in terms of stability and structural specificity. The
      peptide sequence (CGGGEELLKKLEE LLKKG) used was originally designed for a four
      helix bundle. The TASPs were analyzed using CD spectroscopy, chemical
      denaturation studies, NMR spectroscopy, sedimentation equilibria studies, and
      hydrophobic dye binding studies to determine the effect of a single peptide
      sequence when incorporated into bundles with different numbers of helices. If the
      design was indeed idealized for a four-helix bundle, then the five- and six-helix
      bundles should be less stable and manifest lower conformational specificity. The
      TASPs all demonstrated high stability and cooperative unfolding. However, the
      four-helix bundle was found to be significantly more stable and nativelike
      compared to the five- and six-helix bundles. This suggests that the peptide
      sequence is specific to the four-helix bundle, as designed. This result
      demonstrates the ability to design de novo proteins with specified structure, not
      just generic stability.

PMID- 17554753
TI  - Estimation of the marginal survival time in the presence of dependent competing
      risks using inverse probability of censoring weighted (IPCW) methods.
AB  - In medical studies, there is interest in inferring the marginal distribution of a
      survival time subject to competing risks. The Kyushu Lipid Intervention Study
      (KLIS) was a clinical study for hypercholesterolemia, where pravastatin treatment
      was compared with conventional treatment. The primary endpoint was time to events
      of coronary heart disease (CHD). In this study, however, some subjects died from
      causes other than CHD or were censored due to loss to follow-up. Because the
      treatments were targeted to reduce CHD events, the investigators were interested
      in the effect of the treatment on CHD events in the absence of causes of death or
      events other than CHD. In this paper, we present a method for estimating
      treatment group-specific marginal survival curves of time-to-event data in the
      presence of dependent competing risks. The proposed method is a straightforward
      extension of the Inverse Probability of Censoring Weighted (IPCW) method to
      settings with more than one reason for censoring. The results of our analysis
      showed that the IPCW marginal incidence for CHD was almost the same as the lower
      bound for which subjects with competing events were assumed to be censored at the
      end of all follow-up. This result provided reassurance that the results in KLIS
      were robust to competing risks.

PMID- 17554754
TI  - Primary effusion lymphoma: a series of 4 cases and review of the literature with
      emphasis on cytomorphologic and immunocytochemical differential diagnosis.
AB  - BACKGROUND: Primary effusion lymphoma (PEL) is a human herpes virus-8 (HHV-8)
      associated and very rare type of lymphoma usually confined to the body cavities
      and commonly observed in human immunodeficiency virus (HIV)-infected patients. A
      comparison was made between the cytologic and immunocytochemical features of 4
      cases of PEL encountered in the authors' department with those reported to date
      in the literature. METHODS: A comprehensive comparison of the cytologic and
      immunocytochemical features of the 4 cases with those reported in the literature
      was conducted. RESULTS: Cytologically, the most consistent features of the 4
      cases and those in the literature included large cell size, moderate to abundant
      cytoplasm, a single nucleus in most cells with occasional bi- or multinucleated
      giant cells, single to multiple prominent nucleoli, and coarse chromatin.
      Immunocytochemically, only 2 (50%) of the current cases were of the null
      phenotype compared with 93% of cases in the literature; the other 2 cases had a T
      cell phenotype. Activation markers were expressed in 50% and 78% of the current
      cases and the literature cases, respectively. Positivity for HHV-8 was proven in
      the 4 cases by immunocytochemistry. CONCLUSIONS: Cytomorphologically, PEL
      exhibits features bridging large cell immunoblastic and anaplastic large cell
      lymphoma. Although it is usually of null-phenotype, it may occasionally express B
      cell or T-cell markers, rendering its distinction difficult from other
      lymphomatous effusions on a cytologic and immunocytochemical basis alone.
      Therefore, HHV-8 detection is an essential confirmatory ancillary test in
      suspected cases of PEL.

PMID- 17554755
TI  - Spectrum of head and neck lesions diagnosed by fine-needle aspiration cytology in
      the pediatric population.
AB  - Fine-needle aspiration cytology (FNAC) of the head and neck region is well
      accepted as a diagnostic procedure in the adult population. FNAC in the pediatric
      population is gaining acceptance as clinicians add this technique to the
      diagnostic armamentarium. An experience with FNAC of the head and neck region in
      the pediatric population is described from 2 large inner-city hospitals. Eighty
      five cases were retrieved from patients age <18 years. In 52 cases, clinical or
      surgical follow-up was obtained and among these cases the specificity and
      sensitivity of FNA was 93% and 100%, respectively. The high specificity of FNAC
      allows the clinician to be confident of malignancy in a clinically suspicious
      lesion of the head and neck in a pediatric patient.

PMID- 17554756
TI  - Physical aggression as a function of perceived fighting ability and provocation:
      an experimental investigation.
AB  - In three studies, Resource Holding Power (RHP) and provocation were manipulated
      in scenarios involving a young person in a bar with friends. In Study 1, teenage
      men reported lower likelihood of responding with physical aggression when
      insulted as levels of three RHP cues (size, allies and reputation) increased,
      effects that were accentuated by combinations of high-RHP cues; in the second
      part of this study, they consistently rated an insult to their girlfriend as the
      most provoking from a range of possible provocations, chosen on theoretical and
      empirical grounds. Study 2 replicated the results of the first part of Study 1 in
      samples of men and women in their twenties, although the effects were weaker at
      low levels of RHP. Study 3 combined a high- or low-provoking event, with low,
      medium or high RHP, and a wider range of response choices. As expected, direct
      aggression increased as provocation increased and RHP decreased. Delayed
      aggressive responses, including revenge fantasies, were highest in response to
      high provocation and high RHP. Findings are discussed in relation to theoretical
      models of aggressive motivation.

PMID- 17554758
TI  - Dietary variation and stress among prehistoric Jomon foragers from Japan.
AB  - Current archaeological evidence indicates that greater dietary reliance on marine
      resources is recorded among the eastern Jomon, while plant dependence prevailed
      in western/inland Japan. The hypothesis that the dietary choices of the
      western/inland Jomon will be associated with greater systemic stress is tested by
      comparing carious tooth and enamel hypoplasia frequencies between the eastern and
      western/inland Jomon. Demographic collapse coincides with climate change during
      the Middle to Late Jomon period, suggesting dwindling resource availability. It
      is hypothesized that this change was associated with greater systemic stress
      and/or dietary change among the Middle to Late Jomon. This hypothesis is tested
      by comparing enamel hypoplasia and carious tooth frequencies between Middle to
      Late and Late to Final Jomon foragers. Enamel hypoplasia was significantly more
      prevalent among the western/inland Jomon. Such findings are consistent with
      archaeological studies that argue for greater plant consumption and stresses
      associated with seasonal resource depletion among the western/inland Jomon.
      Approximately equivalent enamel hypoplasia frequencies between Middle to Late and
      Late to Final Jomon foragers argues against a demographic collapse in association
      with diminished nutritional returns. Significant differences in carious tooth
      frequencies are, however, observed between Middle to Late and Late to Final Jomon
      foragers. These results suggest a subsistence shift during the Middle to Late
      Jomon period, perhaps in response to a changed climate. The overall patterns of
      stress documented by this study indicate wide-spread environmentally directed
      biological variation among the prehistoric Jomon.

PMID- 17554759
TI  - Human skeletal remains from Sabana de Bogota, Colombia: a case of Paleoamerican
      morphology late survival in South America?
AB  - Human skeletal remains of the first Americans are scarce, especially in North
      America. In South America the situation is less dramatic. Two important
      archaeological regions have generated important collections that allow the
      analysis of the cranial morphological variation of the Early Americans: Lagoa
      Santa, Brazil, and Sabana de Bogota, Colombia. Human crania from the former
      region have been studied by one of us (WAN) and collaborators, showing that the
      cranial morphology of the first South Americans was very different from that
      prevailing today in East Asia and among Native Americans. These results have
      allowed for proposing that the New World may have been colonized by two different
      biological populations in the final Pleistocene/early Holocene. In this study, 74
      human skulls dated between 11.0 and 3.0 kyr, recovered in seven different sites
      of Sabana de Bogota, Colombia, were compared with the world cranial variation by
      different multivariate techniques: Principal Components Analysis,
      Multidimensional Scaling, and Cluster of Mahalanobis distance matrices. The
      Colombian skeletal remains were divided in two chronological subgroups:
      Paleocolombians (11.0-6.0 kyr) and Archaic Colombians (5.0-3.0 kyr). Both
      quantitative techniques generated convergent results: the Paleocolombians show
      remarkable similarities with Lagoa Santa and with modern Australo-Melanesians.
      Archaic Colombians exhibited the same morphological patterns and associations.
      These findings support our long-held proposition that the early American
      settlement may have involved two very distinct biological populations coming from
      Asia. On the other hand, they suggest the possibility of late survivals of the
      Paleoamerican pattern not restricted to isolated or marginal areas, as previously
      thought.

PMID- 17554760
TI  - Brief communication: menarche is related to fat distribution.
AB  - The energy demands of pregnancy and lactation together with the accumulation of
      stored fat in human females during development suggest that a critical level of
      fat may be required for menarche; but multivariate analyses have supported the
      alternative view that skeletal growth is the main factor. However, significant
      differences between upper- and lower-body (gluteofemoral) fat suggest that fat
      distribution may be more relevant than total fat. Using cross-sectional data from
      the third National Health and Nutrition Examination Survey (NHANES III) for
      females aged 10-14, we show that menarche is more closely related to fat
      distribution than to skeletal maturity. Unit increases in hip circumference are
      associated with 24% higher odds of menarche while increases in waist
      circumference and triceps skinfold lower the odds by 7 and 9%, respectively.
      Those with menarche despite low levels of total body fat have relatively more fat
      stored in gluteofemoral depots than those without menarche or those with menarche
      and greater total amounts of fat. In young women with completed growth, age at
      menarche is negatively related to hip and thigh circumference and positively
      related to waist circumference, stature, and biiliac breadth; and blood leptin
      levels are much more strongly related to gluteofemoral than upper-body fat,
      suggesting that leptin may convey information about fat distribution to the
      hypothalamus during puberty. Fat distribution may be relevant because
      gluteofemoral fat may provide neurodevelopmentally important fatty acid reserves.

PMID- 17554761
TI  - Role of wild plant foods among late Holocene hunter-gatherers from Central and
      North Patagonia (South America): an approach from dental evidence.
AB  - This study evaluates the role of plant foods in the subsistence of hunter
      gatherers that inhabited the Central East, Northwest, and Northeast Patagonia
      (Argentina) during the late Holocene (ca. 3,000-500 years BP). The goal of the
      present study is to assess the temporal variation of dental caries ratio and wear
      rate in skeletal samples to ascertain if the biological information supports the
      dietary shift toward greater consumption of wild plant foods around 1,500 years
      BP, suggested by other types of evidence. The authors registered caries,
      antemortem and postmortem tooth loss, and tooth wear from eight samples belonging
      to hunter-gatherers from Patagonia for which chronological sequences from early
      late Holocene (ca. 3,000-1,500 years BP) up to final late Holocene (ca. 1,500-500
      years BP) are available. The results indicate that caries percentages in
      Patagonian samples fall within the range established for hunter-gatherers but
      there are significant geographical differences. In addition, caries ratio does
      not change significantly through time, so the amount of carbohydrates consumed
      seems to have remained fairly constant since 3,000 years BP. In contrast, there
      is a marked temporal trend toward the reduction of wear rates in the three areas,
      suggesting a faster rate in early late Holocene than in final late Holocene.
      These results would reflect a change to less hard and/or abrasive diets in the
      final late Holocene, probably owing to differences in food processing methods
      employed.

PMID- 17554762
TI  - Centrosomal-ciliary gene CEP290/NPHP6 mutations result in blindness with
      unexpected sparing of photoreceptors and visual brain: implications for therapy
      of Leber congenital amaurosis.
AB  - Mutations in the centrosomal-ciliary gene CEP290/NPHP6 are associated with
      Joubert syndrome and are the most common cause of the childhood recessive
      blindness known as Leber congenital amaurosis (LCA). An in-frame deletion in
      Cep290 shows rapid degeneration in the rod-rich mouse retina. To explore the
      mechanisms of the human retinal disease, we studied CEP290-LCA in patients of
      different ages (7-48 years) and compared results to Cep290-mutant mice.
      Unexpectedly, blind CEP290-mutant human retinas retained photoreceptor and inner
      laminar architecture in the cone-rich central retina, independent of severity of
      visual loss. Surrounding the cone-rich island was photoreceptor loss and
      distorted retina, suggesting neural-glial remodeling. The mutant mouse retina at
      4-6 weeks of age showed similar features of retinal remodeling, with altered
      neural and synaptic laminae and Muller glial activation. The visual brain
      pathways in CEP290-LCA were anatomically intact. Our findings of preserved foveal
      cones and visual brain anatomy in LCA with CEP290 mutations, despite severe
      blindness and rapid rod cell death, suggest an opportunity for visual restoration
      of central vision in this common form of inherited blindness.

PMID- 17554763
TI  - Polymorphic background of methionine synthase reductase modulates the phenotype
      of a disease-causing mutation.
AB  - Methionine synthase reductase (MTRR) is the locus of the cblE class of inborn
      errors of cobalamin metabolism that is characterized by megaloblastic anemia and
      homocystinuria. Two highly prevalent SNPs, c.66A>G (p.Ile22Met) and c.524C>T
      (p.Ser175Leu), are found in the MTRR gene. On the basis of the allele frequency
      of these amino acids and sequence comparison with members of the same family of
      proteins, the p.Ile22/p.Ser175 sequence is designated as wild type. While
      characterizing a pathogenic methionine synthase reductase (MSR) mutation,
      c.166G>A (p.Val56Met), we discovered an interaction between the mutation and one
      of the polymorphic sites. Thus, when the p.Val56Met mutant was initially
      expressed in the p.Ile22/p.Ser175 background, we were surprised to find that
      kinetically, it was virtually indistinguishable from wild-type protein. To
      determine if the polymorphisms interacted with the p.Val56Met mutation, it was
      expressed in all four possible genetic backgrounds. We found that in the
      p.Ile22Met background, the p.Val56Met mutation impacted the kinetics of MSR and
      an approximately three- to 10-fold higher concentration of the
      p.Ile22Met/p.Val56Met mutant was required for maximal activation of methionine
      synthase vs. the range seen with wild-type MSR variants. A comparable (three- to
      seven-fold) diminution in MSR activity was observed in extracts of fibroblast
      cells from patients carrying the p.Val56Met mutation on one MSR allele and a null
      mutation on the other. These results predicted that the patient allele encodes
      the p.Val56Met mutation and the p.Ile22Met variation, which was confirmed by
      sequence analysis. This study reveals how a genetic variation can modulate
      phenotypic expression of a disease-causing mutation.

PMID- 17554764
TI  - Transgenic mice expressing a dual, CRE-inducible reporter for the analysis of
      axon guidance and synaptogenesis.
AB  - Improved and modular tools are needed for the neuroanatomical dissection of CNS
      axonal tracts, and to study the cell-intrinsic and cell-extrinsic cues that
      govern their assembly and plasticity. Here we describe a general purpose
      transgenic tracer that can be used to visualize axonal tracts and synaptic
      terminals in any region of the embryonic neural tube or postnatal CNS, on any
      wild type or mutant genetic background. The construct permits CRE-inducible
      expression of a dicistronic axonal marker encoding two surface reporter proteins:
      a farnesylated GFP and the human Placental Alkaline Phosphatase (PLAP). Both
      proteins localize alongside the neuronal surface, permitting the concomitant
      detection of cell body, neurites, and presynaptic and postsynaptic sites in the
      same neuron. This provides a CRE-inducible dual system for imaging neural
      circuits in vivo, and to study their assembly and remodeling in cultured neurons,
      neural stem cells, and tissue explants derived from the reporter line. Unlike
      existing lines, this reporter does not encode a ubiquitously expressed, floxable
      LacZ gene, permitting the simultaneous analysis of beta galactosidase activity in
      mutant lines.

PMID- 17554765
TI  - Hybrid silica-nanocrystal-organic dye superstructures as post-encoding
      fluorescent probes.

PMID- 17554766
TI  - Formal synthesis of (-)-aphanorphine using sequential photomediated radical
      reactions of dithiocarbamates.

PMID- 17554767
TI  - Highly enantioselective aryl additions of [AlAr3(thf)] to ketones catalyzed by a
      titanium(IV) catalyst of (S)-binol.

PMID- 17554768
TI  - Environmentally friendly methodologies of nanostructure synthesis.
AB  - Environmentally friendly synthetic methodologies have gradually been implemented
      as viable techniques in the synthesis of a range of nanostructures. In this work,
      we focus on the application of green-chemistry principles to the synthesis of
      complex metal oxide and fluoride nanostructures. In particular, we describe
      advances in the use of the molten-salt synthetic methods, hydrothermal protocols,
      and template-directed techniques as environmentally sound, socially responsible,
      and cost-effective methodologies that allow us to generate nanomaterials without
      the need to sacrifice sample quality, purity, and crystallinity, while allowing
      control over size, shape, and morphology.

PMID- 17554769
TI  - Electric-field-directed assembly of biomolecular-derivatized nanoparticles into
      higher-order structures.
AB  - Multilayered structures composed of biomolecule-derivatized nanoparticles can be
      fabricated by electric-field-directed self-assembly. A microelectrode-array
      device facilitates the rapid parallel electrophoretic transport and binding of
      biotin and streptavidin fluorescent nanoparticles to specific sites on the
      microarray. Control of the current, voltage, and activation time of each of the
      400-microarray electrodes allows a combinatorial approach to optimize
      nanoparticle binding. Under optimal conditions, nanoparticle layers form within
      15 s of microelectrode activation, and the directed assembly of more than 50
      alternate layers of nanoparticles is complete within an hour. The final
      multilayered structures are removed from the support by a relatively simple lift
      off process. The electric-field process allows the parallel patterned assembly of
      multilayer structures using extremely low concentrations of nanoparticles and
      produces minimal nonspecific binding to unactivated sites. These results are
      significant for the development of rapid, maskless nanofabrication and
      hierarchical integration of biomolecular-derivatized nanocomponents into higher
      order materials and devices.

PMID- 17554770
TI  - A mechanistic and kinetic study of the beta-lactone hydrolysis of Salinosporamide
      A (NPI-0052), a novel proteasome inhibitor.
AB  - The aim of the present study was to investigate the mechanism of aqueous
      degradation of Salinosporamide A (NPI-0052; 1), a potent proteasome inhibitor
      that is currently in Phase I clinical trials for the treatment of cancer and is
      characterized by a unique beta-lactone-gamma-lactam bicyclic ring structure. The
      degradation of 1 was monitored by HPLC and by both low- and high-resolution mass
      spectral analyses. Apparent first-order rate constants for the degradation at 25
      degrees C were determined in aqueous buffer solutions (ionic strength 0.15 M
      adjusted with NaCl) at various pH values in the range of 1 to 9. Degradation
      kinetics in water and in deuterium oxide were compared as a mechanistic probe.
      The studies were performed at pH (pD) 4.5 at 25 degrees C. To further confirm the
      reaction mechanism, the degradation was also performed in (18)O-enriched water
      and the degradation products subjected to HPLC separation prior to mass spectral
      analysis. Solubility and stability in (SBE)(7m)-beta-cyclodextrin (Captisol)
      solutions were also determined. The hydrolytic degradation of 1, followed by both
      HPLC and LC/MS, showed that the drug in aqueous solutions gives a species with a
      molecular ion consistent with the beta-lactone hydrolysis product (NPI-2054; 2).
      This initial degradant further rearranges to a cyclic ether (NPI-2055; 3) via an
      intramolecular nucleophilic displacement reaction. The kinetic results showed
      that the degradation of 1 was moderately buffer catalyzed (general base) and the
      rate constants were pH independent in the range of 1-5 and base dependent above
      pH 6.5. No acid catalysis was observed. The kinetic deuterium solvent isotope
      effect (KSIE) was 3.1 (kH/kD) and a linear proton inventory plot showed that the
      rate-determining step involved only a single proton transfer. This suggested that
      a neighboring hydroxyl group (as opposed to a second water molecule) facilitated
      water attack at pD 4.5. Mass spectral analysis from the (18)O-labeling studies
      proved that the mechanism involves acyl-oxygen bond cleavage and not a carbonium
      ion mechanism. 1 is unstable in water (t(90%) <or= 33 min at pH <5) and degrades
      via beta-lactone hydrolysis involving a normal ester hydrolysis mechanism
      (addition-elimination) resulting in acyl-oxygen bond cleavage. Captisol
      solubilized and stabilized 1 in aqueous solutions.

PMID- 17554771
TI  - Exploring the role of context-dependent hippocampal activity in spatial
      alternation behavior.
AB  - In a continuous T-maze spatial alternation task, CA1 place cells fire
      differentially on the stem of the maze as rats are performing left- and right
      turn trials (Wood et al. (2000) Neuron 27:623-633). This context-dependent
      hippocampal activity provides a potential mechanism by which animals could solve
      the alternation task, as it provides a cue that could prime the appropriate goal
      choice. The aim of this study was to examine the relationship between context
      dependent hippocampal activity and spatial alternation behavior. We report that
      rats with complete lesions of the hippocampus learn and perform the spatial
      alternation task as well as controls if there is no delay between trials,
      suggesting that the observed context-dependent hippocampal activity does not
      mediate alternation behavior in this task. However lesioned rats are
      significantly impaired when delays of 2 or 10 s are interposed. Recording
      experiments reveal that context-dependent hippocampal activity occurs in both the
      delay and no-delay versions of the task, but that in the delay version it occurs
      during the delay period, and not on the stem of the maze. These data are
      consistent with a role for context-dependent hippocampal activity in delayed
      spatial alternation, but suggest that, according to specific task demands and
      memory load, the activity may be generated by different mechanisms and/or in
      different brain structures.

PMID- 17554772
TI  - Processing idiothetic cues to remember visited locations: hippocampal and
      vestibular contributions to radial-arm maze performance.
AB  - This research examined whether rats can use idiothetic cues to form spatial
      memories in the radial-arm maze (RM) and whether the hippocampus is involved in
      such ability. A possible contribution of the vestibular system to RM performance
      was also investigated. Rats with excitotoxic hippocampal lesions and sham
      operated controls were trained on two versions of the RM task. In the Light
      condition, a unique visual insert was apposed on each arm floor and rats could
      choose which arm to enter next by relying on visual and/or idiothetic stimuli. In
      the Dark condition, the task was administered in darkness and success required
      processing of idiothetic cues to remember visited locations on the maze. In
      experiment 1, the performance of lesioned rats was impaired in the Light
      condition, but both control and lesioned rats learned to avoid already visited
      arms. In the Dark condition, the performance of controls improved over time
      whereas a severe deficit was observed in rats with hippocampal lesions. Thus,
      control rats, but not hippocampal lesioned rats, can form spatial memories by
      processing idiothetic inputs. Experiment 2 showed that vestibular lesions disrupt
      performance in both the Light and the Dark conditions and confirmed that rats use
      idiothetic information, especially vestibular cues, while navigating in the RM.
      Therefore, cues generated during locomotion play an important role in hippocampal
      dependent spatial memory.

PMID- 17554774
TI  - Highly enantioselective alkynylation of aldehydes using a new
      BINOL/Ti(OiPr)4/chiral sulfonamide catalyst system.
AB  - A series of sulfonamides (2-4) were prepared from natural amino acids and used as
      additives in the BINOL-Ti(OiPr)(4) catalyzed enantioselective alkynylation of
      aldehydes. The reactions proceeded smoothly with good yields and very high ee's
      (up to 99%) in most cases.

PMID- 17554775
TI  - Stereoselective toxicokinetics and tissue distribution of ethofumesate in
      rabbits.
AB  - The stereoselective toxicokinetics of ethofumesate enantiomers following a single
      intravenous (i.v.) administration at doses of 30 mg/kg were investigated in
      rabbits. Plasma concentrations of (+)- and (-)-ethofumesate were analyzed by a
      validated chiral HPLC method that involved extraction of plasma with organic
      solvent followed by separation on a cellulose-Tris-(3,5-dimethylphenylcarbamate)
      based chiral column and quantification by UV absorbance at 230 nm. Plasma
      concentration-time curves after i.v. administration were best described by an
      open two-compartment model. The concentration of the (-)-enantiomer decreased
      more rapidly than that of the (+)-enantiomer. Significant differences in
      toxicokinetic parameters between the two enantiomers indicated that
      stereoselective behavior occurred with the (-)-enantiomer being preferentially
      metabolized and eliminated.

PMID- 17554777
TI  - Computing van der Waals energies in the context of the rotamer approximation.
AB  - The rotamer approximation states that protein side-chain conformations can be
      described well using a finite set of rotational isomers. This approximation is
      often applied in the context of computational protein design and structure
      prediction to reduce the complexity of structural sampling. It is an effective
      way of reducing the structure space to the most relevant conformations. However,
      the appropriateness of rotamers for sampling structure space does not imply that
      a rotamer-based energy landscape preserves any of the properties of the true
      continuous energy landscape. Specifically, because the energy of a van der Waals
      interaction can be very sensitive to small changes in atomic separation,
      meaningful van der Waals energies are particularly difficult to calculate from
      rotamer-based structures. This presents a problem for computational protein
      design, where the total energy of a given structure is often represented as a sum
      of precalculated rigid rotamer self and pair contributions. A common way of
      addressing this issue is to modify the van der Waals function to reduce its
      sensitivity to atomic position, but excessive modification may result in a
      strongly nonphysical potential. Although many different van der Waals
      modifications have been used in protein design, little is known about which
      performs best, and why. In this paper, we study 10 ways of computing van der
      Waals energies under the rotamer approximation, representing four general
      classes, and compare their performance using a variety of metrics relevant to
      protein design and native-sequence repacking calculations. Scaling van der Waals
      radii by anywhere from 85 to 95% gives the best performance. Linearizing and
      capping the repulsive portion of the potential can give additional improvement,
      which comes primarily from getting rid of unrealistically large clash energies.
      On the other hand, continuously minimizing individual rotamer pairs prior to
      evaluating their interaction works acceptably in native-sequence repacking, but
      fails in protein design. Additionally, we show that the problem of predicting
      relevant van der Waals energies from rotamer-based structures is strongly
      nonpairwise decomposable and hence further modifications of the potential are
      unlikely to give significant improvement.

PMID- 17554778
TI  - Crystal structure of glutathione reductase Glr1 from the yeast Saccharomyces
      cerevisiae.
AB  - Yeast glutathione (GSH) reductase Glr1 is a dimeric flavo-oxidoreductase involved
      in cytoplasmic and mitochondrial redox regulatory systems. It reduces the
      oxidized GSH GSSG to the reduced form, GSH with NADPH as electron donor and FAD
      as coenzyme. Crystal structures and enzymatic mechanisms of GSH reductases from
      Escherichia coli and Homo sapiens have been well investigated, whereas the
      structural properties of yeast Glr1 remain unknown. Herein, we overexpressed
      Saccharomyces cerevisiae Glr1 in Pichia pastoris GS115 and determined its crystal
      structure at 2.40 A resolution. Although the overall structure and the active
      site are much conserved, obvious variety was found at the interface of Glr1
      monomers when superimposed against the homolog from E. coli or human. The
      nonconserved C239 is exposed to the solvent and accessible to GSH or GSSG
      enriched in a microenvironment around the Glr1 molecules, leading to the partial
      and transient glutathionylation, as primarily identified from the 2Fo-Fc electron
      density map and further confirmed by biochemical assays. Meanwhile N278 at the
      vicinity of NADP-binding pocket was artificially glycosylated when
      heterogeneously overexpressed in P. pastoris. The highly motile oligosaccharide
      chain linked to N278 of the recombinant Glr1 interferes with the entry of NADPH,
      which results in a dramatic increase of Km for NAPDH and a significant decrease
      of turnover number, when compared with the native protein.

PMID- 17554779
TI  - An automated decision-tree approach to predicting protein interaction hot spots.
AB  - Protein-protein interactions can be altered by mutating one or more "hot spots,"
      the subset of residues that account for most of the interface's binding free
      energy. The identification of hot spots requires a significant experimental
      effort, highlighting the practical value of hot spot predictions. We present two
      knowledge-based models that improve the ability to predict hot spots: K-FADE uses
      shape specificity features calculated by the Fast Atomic Density Evaluation
      (FADE) program, and K-CON uses biochemical contact features. The combined K
      FADE/CON (KFC) model displays better overall predictive accuracy than
      computational alanine scanning (Robetta-Ala). In addition, because these methods
      predict different subsets of known hot spots, a large and significant increase in
      accuracy is achieved by combining KFC and Robetta-Ala. The KFC analysis is
      applied to the calmodulin (CaM)/smooth muscle myosin light chain kinase (smMLCK)
      interface, and to the bone morphogenetic protein-2 (BMP-2)/BMP receptor-type I
      (BMPR-IA) interface. The results indicate a strong correlation between KFC hot
      spot predictions and mutations that significantly reduce the binding affinity of
      the interface.

PMID- 17554780
TI  - Crystal structure of calcium binding protein-1 from Entamoeba histolytica: a
      novel arrangement of EF hand motifs.
AB  - Calcium plays a pivotal role in the pathogenesis of amoebiasis, a major disease
      caused by Entamoeba histolytica. Several EF-hand containing calcium-binding
      proteins (CaBPs) have been identified from E. histolytica. Even though these
      proteins have very high sequence similarity, they bind to different target
      proteins in a Ca2+ dependent manner, leading to different functional pathways
      (Yadava et al., Mol Biochem Parasito 1997;84:69-82; Chakrabarty et al., J Biol
      Chem 2004;279:12898-12908) The crystal structure of the Entamoeba histolytica
      calcium binding protein-1 (EhCaBP1) has been determined at 2.4 A resolution. The
      crystals were grown using MPD as precipitant and they belong to P6(3) space group
      with unit cell parameters of a = 95.25 A, b = 95.25 A, c = 64.99 A. Only two out
      of the four expected EF hand motifs could be modeled into the electron density
      map and the final model refined to R factor of 25.6% and Free_R of 28%. Unlike
      CaM, the first two EF hand motifs in EhCaBP1 are connected by a long helix and
      form a dumbbell shaped structure. Owing to domain swapping oligomerization three
      EhCaBP1 molecules interact in a head to tail manner to form a triangular trimer.
      This arrangement allows the EF-hand motif of one molecule to interact with that
      of an adjacent molecule to form a two EF-hand domain similar to that seen in the
      N-terminal domain of the NMR structure of CaBP1, calmodulin and troponin C. The
      oligomeric state of EhCaBP1 results in reduced flexibility between domains and
      may be responsible for the more limited set of targets recognized by EhCaBP1.

PMID- 17554781
TI  - Crystal structure of the tRNA-specific adenosine deaminase from Streptococcus
      pyogenes.

PMID- 17554782
TI  - Tilted properties of the 67-78 fragment of alpha-synuclein are responsible for
      membrane destabilization and neurotoxicity.
AB  - Alpha-synuclein is a 140 residue protein associated with Parkinson's disease.
      Intraneural inclusions called Lewy bodies and Lewy neurites are mainly composed
      of alpha-synuclein aggregated into amyloid fibrils. Other amyloidogenic proteins,
      such as the beta amyloid peptide involved in Alzheimer's disease and the prion
      protein (PrP) associated with Creuztfeldt-Jakob's disease, are known to possess
      "tilted peptides". These peptides are short protein fragments that adopt an
      oblique orientation at a hydrophobic/hydrophilic interface, which enables
      destabilization of the membranes. In this paper, sequence analysis and molecular
      modelling predict that the 67-78 fragment of alpha-synuclein is a tilted peptide.
      Its destabilizing properties were tested experimentally. The alpha-synuclein 67
      78 peptide is able to induce lipid mixing and leakage of unilamellar liposomes.
      The neuronal toxicity, studied using human neuroblastoma cells, demonstrated that
      the alpha-synuclein 67-78 peptide induces neurotoxicity. A mutant designed by
      molecular modelling to be amphipathic was shown to be significantly less
      fusogenic and toxic than the wild type. In conclusion, we have identified a
      tilted peptide in alpha-synuclein, which could be involved in the toxicity
      induced during amyloidogenesis of alpha-synuclein.

PMID- 17554783
TI  - Folding propensity and biological activity of peptides: New insights from
      conformational properties of a novel peptide derived from Vitreoscilla
      haemoglobin.
AB  - The synthetic peptide Vitr-p-13 (YPIVGQELLGAIK-NH(2)), derived from the bacterial
      dimeric Vitreoscilla haemoglobin (VHb) in the position 95-107, is characterized
      by a pre-eminent "statistical coil" conformation in water as demonstrated by CD
      experiments and long time-scale MD simulations. In particular, Vitr-p-13 does not
      spontaneously adopt an alpha-helix folding in water, but it is rather
      preferentially found in beta-hairpin-like conformations. Long time-scale MD
      simulations have also shown that Vitr-p-13 displays a "topological-trigger" which
      initiates alpha-helix folding within residues 7-10, exactly like seen in the
      temporins, a group of linear, membrane-active antimicrobial peptides of similar
      length. At variance with temporins, in Vitr-p-13 such a process is energetically
      very demanding (+10 kJ/mol) in water at 300 K, and the peptide was found to be
      unable to bind model membranes in vitro and was devoid of antimicrobial activity.
      The present results, compared with previous studies on similar systems,
      strengthen the hypothesis of the requirement of a partial folding when still in
      aqueous environment to allow a peptide to interact with cell-membranes and
      eventually exert membrane perturbation-related antibiotic effects on target
      microbial cells.

PMID- 17554784
TI  - Selective overexpression of gamma1 laminin in astrocytes in amyotrophic lateral
      sclerosis indicates an involvement in ALS pathology.
AB  - Our earlier studies indicate that the KDI tripeptide of gamma1 laminin reverts
      paralysis and protects adult rat CNS from excitotoxicity of glutamate and from
      oxidative stress. Here we show that gamma1 laminin is selectively overexpressed
      in reactive astrocytes of the amyotrophic lateral sclerosis (ALS) spinal cord,
      with both gray and white matter astrocytes overexpressing gamma1 laminin.
      Intensely gamma1 laminin-positive, aggressive-looking reactive astrocytes of the
      lateral columns of both cervical and thoracic spinal cord surround the lateral
      ventral horns and roots and extend into the area of the lateral corticospinal
      tract. In the cervical ALS spinal cord, large numbers of strongly gamma1 laminin
      immunoreactive astrocytes are also present in the dorsal columns of the ascending
      sensory pathways. No other laminin or any other ALS-associated protein localizes
      in this manner. This unique distribution of gamma1 laminin-immunoreactive
      astrocytes in the ALS white matter together with our recent results on the
      efficacy of the KDI domain as a neuronal protector strongly suggest that gamma1
      laminin may be expressed by astrocytes of the ALS spinal cord as a protective
      measure intended to aid neuronal survival. Further comparative studies on ALS
      spinal cord tissues and those of the animal models of ALS are needed to clarify
      the specific role of gamma1 laminin and its KDI domain in ALS and its putative
      interactions with the additional ALS-associated factors, such as excitotoxicity,
      oxidative stress, and neurofilament accumulation. Most importantly, further
      studies are urgently needed to test the potential of the KDI tripeptide as a
      therapeutic treatment for ALS.

PMID- 17554785
TI  - Identification of a novel p53 in-frame deletion in a Li-Fraumeni-like family.
AB  - We describe a 2-year-old female with a completely resected cerebral pilocytic
      astrocytoma who subsequently developed B-progenitor acute lymphoblastic leukemia
      (ALL). Her father and paternal uncle were previously diagnosed with glioblastoma
      multiforme. Sequence analysis of the patient's p53 gene revealed a novel germline
      three base-pair deletion (339_341delCTT) in exon 4, resulting in removal of an
      evolutionarily conserved phenylalanine amino acid residue at codon 113. The same
      mutation was found in the patient's two clinically unaffected siblings. The in
      frame deletion we describe has not previously been reported and adds to our
      understanding of the biologic effects of p53 gene mutation in Li-Fraumeni
      syndrome (LFS).

PMID- 17554786
TI  - Initial testing of cisplatin by the pediatric preclinical testing program.
AB  - BACKGROUND: Cisplatin is one of the most widely used drugs for the treatment of
      solid tumors in adults and children. Here, we report the activity of cisplatin
      against the PPTP panels of childhood cancer xenografts. PROCEDURES: Cisplatin was
      evaluated against 23 cell lines, and 40 xenografts representing brain tumors,
      neuroblastoma, rhabdoid tumors, sarcoma, Wilms tumor, and acute lymphoblastic
      leukemia (ALL). The IC(50) concentration in vitro was determined for 96 hr
      exposure. Solid tumors were grown subcutaneously in immune-deficient mice, and
      tumor dimensions measured weekly. ALL xenografts were inoculated intravenously
      and the percent human CD45(+) cells in the peripheral blood determined weekly.
      The antitumor activity of cisplatin (7 mg/kg administered intraperitoneally on
      Days 0 and 21) was evaluated using time to event (EFS T/C), tumor growth delay
      (tumor volume T/C), and objective response measures. RESULTS: The median IC(50)
      concentration in vitro was 0.87 microM (0.24-4.29 microM), and cisplatin
      exhibited broad range activity. Cisplatin induced significant differences in EFS
      distributions compared to controls in 20/28 solid tumors and 4/8 ALL models.
      Objective responses were observed in 7/28 solid tumor models (25%): partial
      responses in three rhabdomyosarcomas and one Ewing's sarcoma; complete responses
      in one rhabdoid tumor and the medulloblastoma; and a maintained complete response
      in one Wilms tumor. No objective responses were observed in the ALL panel.
      CONCLUSIONS: Cisplatin exhibits significant antitumor activity against a broad
      range of solid tumor xenograft models and limited activity against ALL
      xenografts. This preclinical pattern of activity is generally consistent with
      cisplatin's clinical activity.

PMID- 17554787
TI  - High-grade astrocytoma in very young children.
AB  - BACKGROUND: High-grade astrocytomas are rare in young children, but have been
      reported to have a better prognosis than similar tumors in older patients.
      PROCEDURE: We retrospectively reviewed the clinical characteristics, survival,
      and long-term sequelae for patients younger than 3 years old with high-grade
      astrocytoma, treated at a single institution between 1984 and 2005. RESULTS:
      Sixteen patients were included. Histology included anaplastic astrocytoma (n =
      9), glioblastoma multiforme (n = 5), and malignant glioma (n = 2). All patients
      underwent biopsy or resection, followed by chemotherapy. Six patients received
      scheduled irradiation and six were irradiated at the time of disease progression.
      Ten patients are alive at a median follow-up of 11.6 years (range, 1.7-21.6
      years). 5-year overall survival (OS) was 66.3% (SE 12.2%), and 5-year event-free
      survival (EFS) was 28.6% (SE 12.1%). Age at diagnosis was a significant predictor
      of the hazard of death in a Cox model (HR 2.871, 95%CI 1.015-8.123). Gender and
      histology did not predict OS or EFS. Trends toward improved OS were detected for
      patients with hemispheric tumors and those undergoing complete resection. All
      evaluable survivors (n = 9) had some neurocognitive impairment, with estimated
      overall cognitive ability ranging from significantly delayed to average; all
      survivors attending school (n = 5) performed below grade level on achievement
      testing. Seven of nine evaluable survivors had endocrine dysfunction.
      CONCLUSIONS: Young children with high-grade astrocytoma have better long-term
      overall survival than older patients, but recurrence is common, and most children
      require irradiation. Long-term complications are frequent and often severe.

PMID- 17554788
TI  - Retinoic acid induced downregulation of MYCN is not mediated through changes in
      Sp1/Sp3.
AB  - BACKGROUND: Use of retinoic acid (RA) has become the standard of care in the
      treatment of high risk neuroblastoma (NB). In vitro, RA induces growth arrest and
      differentiation, an effect that likely underlies its activity in the clinical
      setting. An important event in differentiation is the transcriptional
      downregulation of the MYCN oncogene, which is frequently activated in aggressive
      tumors. While it is known that Sp1/Sp3 and E2F are necessary to drive basal MYCN
      expression, the mechanism for its downregulation by RA remains enigmatic. Changes
      in E2F binding have been reported, however these occurred after the actual
      transcriptional response. Here, post-translational modifications of Sp proteins
      were examined as an alternate mechanism of RA-mediated promoter regulation.
      PROCEDURE: Western blot was used to evaluate steady state levels of
      nuclear/cytoplasmic Sp1/Sp3. Promoter binding and DNA conformation were
      determined by gel shift, circular permutation, and chromatin immunoprecipitation
      assays. Immunoprecipitation/western and (32)P-phosphoamino analyses were used to
      detect glycosylation, acetylation, sumoylation, and phosphorylation. RESULTS: RA
      did not affect the cellular level of Sp1/Sp3 proteins, their nuclear/cytoplasmic
      distribution, ability to bind the MYCN promoter, degree of Sp-induced DNA
      bending, or post-translational modifications. CONCLUSIONS: MYCN RA response is
      not mediated solely though the region controlling basal activity. RA may be
      exerting its effects via multiple non-adjacent regulatory regions, potentially
      including basal motifs, either within the MYCN promoter or distally, on the same
      or even different chromosomes. Such cooperative trans-type DNA-protein
      interactions could explain the inaccessibility of this mechanism to the locus
      specific approaches employed up to this point.

PMID- 17554789
TI  - Serum ferritin underestimates liver iron concentration in transfusion independent
      thalassemia patients as compared to regularly transfused thalassemia and sickle
      cell patients.
AB  - Serum ferritin (SF) and liver iron concentration (LIC), as measured by SQUID
      biosusceptometry, were assessed in a convenience sample of transfusion
      independent thalassemia patients (nTx-Thal, n=26), regularly transfused
      thalassemia (Tx-Thal, n=89), or sickle cell patients (SCD, n=45) to investigate
      the severity of iron overload and the relationship between SF and LIC in nTx-Thal
      compared to SCD and Tx-Thal. SF correlated with LIC (RS=0.53, P<0.001), but was
      found to be a poor predictor for LIC. SF was significantly lower (P<0.001) in nTx
      Thal patients than in other groups, despite similar LIC values. The SF-to-LIC
      ratio was significantly lower in nTx-Thal compared to Tx-Thal and SCD patients
      (median of 0.32, 0.87, and 1.2, respectively: P<0.001). Due to underestimation of
      LIC by ferritin levels, chelation treatment may be delayed or misdirected in
      patients with thalassemia intermedia.

PMID- 17554790
TI  - Loss of antibody titers and effectiveness of revaccination in post-chemotherapy
      pediatric sarcoma patients.
AB  - BACKGROUND: Little is known about the effects of chemotherapy on patient antibody
      titers to vaccine-preventable infectious diseases; thus, there is no standard
      protocol for revaccinating post-chemotherapy patients. PROCEDURES: To assess
      losses of detectable antibody titers due to chemotherapy, we retrospectively
      examined antibody titers for tetanus, varicella, measles, mumps, rubella,
      hepatitis B, and polio in 109 pediatric sarcoma patients. We also evaluated
      revaccination data to determine current practices and efficacy of revaccination.
      We limited our sample to osteosarcoma, Ewing sarcoma, and rhabdomyosarcoma
      patients to control for the chemotherapy regimen patients received. RESULTS:
      Patients had pre-treatment detectable antibody titer that fell within the range
      of healthy children's antibody titers. However, 71% of patients had post
      chemotherapy negative titers for at least one infectious disease. Patients most
      commonly had negative titers for hepatitis B (64%). Few patients had negative
      titers for measles (14%), mumps (9%), rubella (4%), polio 1 (0%), polio 2 (2.9%),
      polio 3 (4.8%), tetanus (5%), or varicella (11%). Revaccinations most frequently
      administered were hepatitis B and polio. CONCLUSIONS: Our findings suggest that
      post-chemotherapy patients may need to be revaccinated against certain vaccine
      preventable diseases including hepatitis B, tetanus, varicella, polio, measles,
      mumps, and rubella. Larger studies need to be performed to establish guidelines
      for revaccinating post-chemotherapy pediatric patients.

PMID- 17554791
TI  - Employment status among adult survivors in the Childhood Cancer Survivor Study.
AB  - BACKGROUND: With increased cure, childhood cancer survivors are reaching
      adulthood and seeking employment. Host, disease and treatment risk factors may
      contribute to inability to attain or maintain employment. PROCEDURE: The
      prevalence and risk factors for unemployment were evaluated using self-reported
      employment history in 10,399 childhood cancer survivors and 3,083 siblings >/=
      age 18 in the Childhood Cancer Survivor Study (CCSS). RESULTS: Among survivors,
      5.6% reported unemployment, compared with 1.2% of siblings (odds ratio [OR] 3.7;
      95% confidence interval [CI] 2.6, 5.1). Increased risks were observed within all
      cancer diagnoses. In multivariate analysis, diagnosis of central nervous system
      (CNS) tumor (OR 1.5; 95% CI 1.1, 2.1), bone cancer (OR 1.5; 95% CI 1.0, 2.1),
      treatment with >/=30 Gy cranial radiotherapy (OR 4.0; 95% CI 2.9, 5.5), female
      gender (OR 1.4; 95% CI 1.2, 1.7) and age < 4 years at diagnosis (OR 1.4; 95% CI
      1.1, 1.8) increased risk. Diagnosis of CNS or bone tumor or cranial radiotherapy
      >/=30 Gy remained significant after adjusting for treatment, medical late
      effects, age and gender. Risk of unemployment decreased with attained age
      (OR((year)) 0.89; 95% CI 0.87, 0.91). CONCLUSIONS: Compared to siblings, adult
      childhood cancer survivors are at increased risk for unemployment with highest
      risk defined by diagnosis, treatment and demographic factors.

PMID- 17554793
TI  - Improvement in the outcome of children with germ cell tumors.
AB  - PURPOSE: To describe the clinical characteristics and estimate the survival of
      children and adolescents with germ cell tumors treated with cisplatin-based
      combination chemotherapy according to three different protocols in Brazil.
      METHODS: From 1983 to 1997, 106 patients were treated at the Hospital do Cancer,
      Sao Paulo for a diagnosis of germ cell tumor. We performed a retrospective review
      of the clinical and histopathological data to identify prognostic factors and
      evaluate their outcome. RESULTS: Patients were treated with only surgery (n =
      32), surgery and radiotherapy (n = 1) and chemotherapy (n = 73). From 1983 to
      1986 (period I), there were 30 patients and 21 received chemotherapy according to
      the modified VAB-6 protocol. Twenty-two of 35 patients registered between 1987
      and 1991 (period II) were treated with EPO/VAC combination chemotherapy. From
      1991 to 1997 (period III), there were 41 patients and 31 received chemotherapy
      according to the Brazilian TCG-91 protocol. Important prognostic factors included
      stage (P < 0.001), metastatic status (P < 0.001) and surgical procedure at
      diagnosis (P < 0.001). An incremental improvement in outcomes was noted across
      the periods of treatment (P = 0.070). Five-year OS was respectively 42.9 +/-
      10.8%, 53.9 +/- 11.4% and 80.6 +/- 7.1% for periods I, II, and III for the
      patients who received chemotherapy. CONCLUSION: An improvement in the survival of
      children with germ cell tumors was achieved in the most recent trial (TCG-91)
      with a risk adapted approach incorporating only cisplatin and etoposide. These
      results indicate that in selected patients complex three-agent regimens may not
      be necessary to achieve long term survival.

PMID- 17554792
TI  - Impairments in antifolate transport are common in retinoblastoma tumor samples.
AB  - BACKGROUND: Many patients with retinoblastoma have a genetic predisposition to
      cancer and external beam radiation therapy and alkylating agent chemotherapy may
      increase their risk of secondary malignancy. Identification of effective
      chemotherapy agents for retinoblastoma that are not associated with an elevated
      risk of secondary malignancy would be beneficial. PROCEDURE: Twenty-six specimens
      of fresh retinoblastoma tumor cells were studied in vitro with a PT430
      competitive displacement assay. Differential displacement of the PT430 by
      methotrexate and not trimetrexate was considered indicative of a defect in
      reduced folate carrier (RFC)-mediated transport. Elevations in the accumulation
      of PT430 were considered indicative of dihydrofolate reductase (DHFR)
      amplification. RESULTS: In 9 of the 26 (35%) samples, displacement by
      methotrexate was less than half the displacement by trimetrexate indicative of a
      defect in the RFC. In 5 of the 26 (19%) samples, trimetrexate did not displace
      the PT430. In 7 of 26 (27%) samples, the peak PT430 accumulation was suggestive
      of DHFR overexpression. Overall 9 of 26 (35%) samples had no evidence of a
      transport defect or DHFR overexpression and would be anticipated to be
      potentially sensitive to methotrexate. In 15 of the 26 (58%), no defects existed
      in trimetrexate displacement or DHFR overexpression and would be anticipated to
      be potentially sensitive to trimetrexate. CONCLUSION: These results would support
      consideration of a phase II study to determine the effectiveness of trimetrexate
      for recurrent intra-ocular retinoblastoma.

PMID- 17554794
TI  - Preservation of spleen and brain function in children with sickle cell anemia
      treated with hydroxyurea.
AB  - INTRODUCTION: Chronic organ damage is an insidious process in patients with
      sickle cell anemia (SCA). Although hydroxyurea prevents acute vaso-occlusive
      events, its effects on the preservation of organ function remain undefined.
      PATIENTS AND METHODS: We retrospectively reviewed our single institution
      experience with children with SCA treated with hydroxyurea for clinical disease
      severity, who had optional radionuclide liver-spleen (LS) and brain magnetic
      resonance imaging (MRI)/with angiography (MRA) performed before and during
      therapy. Studies were reviewed by pediatric radiologists blinded to treatment
      status. Demographic and laboratory predictors were modeled using logistic
      regression. RESULTS: A total of 43 children had spleen function measured both at
      baseline and on therapy. After a median of 2.6 years (range, 0.2-8.6 years) of
      hydroxyurea at maximum tolerated dose (MTD), six patients (14%) completely
      recovered splenic function and two (5%) had preserved splenic function. These
      eight children had a greater hemoglobin (Hb) concentration on hydroxyurea therapy
      than those without splenic function (9.1 vs. 8.6 gm/dl, P = 0.01). Of 25 children
      with brain MRI/MRA studies performed before initiating hydroxyurea and on
      therapy, 24 (96%) had no change in brain ischemic lesions compared with pre
      treatment studies, after a median of 2.9 years of treatment. CONCLUSION: These
      retrospective data suggest that hydroxyurea at MTD possibly preserves spleen and
      brain function in children with SCA, and can even result in recovery of splenic
      function. Higher final Hb concentration during therapy is a significant
      laboratory predictor of improved splenic function.

PMID- 17554795
TI  - The molecular biology and clinical features of amyloid neuropathy.
AB  - Neuropathy is often a major manifestation of systemic amyloidosis. It is most
      frequently seen in patients with hereditary transthyretin (TTR) amyloidosis, but
      is also present in 20% of patients with systemic immunoglobulin light chain
      (primary) amyloidosis. Familial amyloid polyneuropathy (FAP) is the most common
      form of inherited amyloidotic polyneuropathy, with clinical and
      electrophysiologic findings similar to neuropathies with differing etiologies
      (e.g., diabetes mellitus). Hereditary amyloidosis is an adult-onset autosomal
      dominant disease with varying degrees of penetrance. It is caused by specific
      gene mutations, but demonstration that a patient has one such mutation does not
      confirm the diagnosis of amyloidosis. Diagnosis requires tissue biopsy with
      demonstration of amyloid deposits either by special histochemical stains or
      electron microscopy. Transthyretin amyloidosis is treated by liver
      transplantation, which eliminates the mutated transthyretin from the blood, but
      for some patients continued amyloid deposition can occur from wild-type (normal)
      transthyretin. Presently, a study is ongoing to determine whether amyloid
      deposition can be inhibited by small organic molecules that are hypothesized to
      affect the fibril-forming ability of transthyretin. Proposed gene therapy with
      antisense oligonucleotides (ASOs) to suppress hepatic transthyretin synthesis is
      effective in a transgenic mouse model but has not yet been tested in humans.

PMID- 17554796
TI  - Relationship between muscle stress and intramuscular pressure during dynamic
      muscle contractions.
AB  - Intramuscular pressure (IMP) has been used to estimate muscle stress indirectly.
      However, the ability of this technique to estimate muscle stress under dynamic
      conditions is poorly characterized. Therefore, the purpose of this study was to
      determine the extent to which IMP is a valid surrogate for muscle stress during
      dynamic contractions. IMP and muscle stress were compared under steady-state
      isotonic conditions and during complex dynamic length changes. During concentric
      contractions the shape of the IMP-velocity curve mimicked the basic shape of the
      force-velocity curve but with much higher variability. For eccentric
      contractions, a precipitous drop in IMP was observed despite increased muscle
      stress. The dissociation between muscle stress and IMP during dynamic
      contractions was partially explained by sensor movement. When the muscle was not
      moving, IMP explained 89% +/- 5% of the variance in muscle force. However, when
      transducer movement occurred the linear relationship between IMP and stress was
      no longer observed. These findings demonstrate the difficulty in interpreting IMP
      under dynamic conditions when sensor movement occurs. They also illustrate the
      need to control transducer movement if muscle stress is to be inferred from IMP
      measurements such as might be desired during clinical gait testing.

PMID- 17554797
TI  - Central activation, muscle performance, and physical function in men infected
      with human immunodeficiency virus.
AB  - Loss of muscle mass and limitations in activity have been reported in persons
      infected with human immunodeficiency virus (HIV), even those who are otherwise
      asymptomatic. The extent to which factors other than muscle atrophy impair muscle
      performance has not been addressed in depth. The purpose of this study was to
      determine the extent of neuromuscular activation of the knee extensors and ankle
      dorsiflexors of 27 men infected with HIV receiving antiretroviral therapy and its
      relationship to muscle performance. The central activation ratio (CAR) was
      determined using superimposed electrical stimulation during maximum voluntary
      contractions. In addition to force and power measurements, muscle cross-sectional
      area and composition was evaluated using computed tomography. Aerobic capacity
      was determined from treadmill exercise testing. Eleven of the subjects had an
      impaired ability to activate the knee extensors (CAR = 0.72 +/- 0.12) that was
      associated with weakness and decreased specific force. The reduced central
      activation was not associated with muscle area, body composition, aerobic
      capacity, CD4 count, or medication regimen. Those individuals with low central
      activation had higher HIV-1 viral loads and were more likely to have a history of
      AIDS-defining illness. These results suggest the possibility of a different
      mechanism contributing to muscle impairment in the current treatment era that is
      associated with impairment of central motor function rather than atrophy. Further
      investigation is warranted in a larger, more diverse population before more
      definitive claims are made.

PMID- 17554798
TI  - Fukutin-related protein localizes to the Golgi apparatus and mutations lead to
      mislocalization in muscle in vivo.
AB  - Mutations in the fukutin-related protein gene (FKRP) are associated with a
      spectrum of diseases from mild limb-girdle muscular dystrophy type 2I to severe
      congenital muscular dystrophy type 1C, muscle-eye-brain disease (MEB), and Walker
      Warburg syndrome (WWS). The effect of mutations on the transportation of the
      mutant proteins may constitute the underlying mechanisms for the pathogenesis of
      these diseases. Here we examined the subcellular localization of mouse and human
      normal and mutant FKRP proteins in cells and in muscle in vivo. Both normal human
      and mouse FKRPs localize in part of the Golgi apparatus in muscle fibers.
      Mutations in the FKRP gene invariably altered the localization of the protein,
      leading to endoplasmic reticulum retention within cells and diminished Golgi
      localization in muscle fibers. Our results therefore suggest that an individual
      missense point mutation can confer at least two independent effects on the
      protein, causing (1) reduction or loss of the presumed glycosyltransferase
      activity directly and (2) mislocalization that could further alter the function
      of the protein. The complexity of the effect of individual missense point
      mutations may partly explain the wide variation of the FKRP-related myopathies.

PMID- 17554799
TI  - RAG2 gene knockout in mice causes fatigue.
AB  - The effect of a disrupted immune system on the neuromuscular system is poorly
      characterized. We compared the strength and fatigue of RAG2(-/-) mice, which lack
      T-cells and B-cells, with immune intact controls. RAG2(-/-) mice demonstrated
      fatigue with shorter inverted hang-times (HT) and voluntary wheel-running (VWR)
      distance and total run times; they increased body weight more slowly but had
      proportionally normal forelimb grip strength (FGS) and VWR speed. Medial rectus
      femoris histopathology showed no change in fiber type proportions, no variation
      in type 2b fiber diameter, and no change in the percentage of central nuclei.
      There was no change in serum creatine kinase (CK) levels. Thus, in RAG2(-/-) mice
      body weight and fatigue were directly affected by a hypoactive immune system.
      Whether these effects were centrally or peripherally mediated is unknown. This
      model may help to explain fatigue in human conditions in which the immune system
      is suppressed or absent.

PMID- 17554800
TI  - Embryology of neural tube defects: information provided by associated
      malformations.
AB  - OBJECTIVES: To get information about embryologic mechanisms of neural tube
      defects (NTD), by studying the associated malformations. METHODS: Eighty three
      cases of NTD, seen at the prenatal diagnosis unit of Rennes University Hospital
      (France) between May 1999 and December 2002, were retrospectively studied. Cases
      with chromosomal anomalies (5/83), cases without available karyotype or
      pathologic examination were excluded. 24 spina bifida, and 27 cephalic forms
      (anencephalies, exencephalies, and encephaloceles) were thus analyzed. RESULTS:
      Only 22/51 cases (43%) were strictly isolated NTD. Anomalies of tissues arising
      from neural crests were noted in 8/51 fetuses (16%), midline or lateralization
      anomalies in 12/51 (24%), and anomalies of mesoblastic tissues in 17/51 (33%). An
      already known syndrome was found in 4/51 cases (8%). CONCLUSION: NDT are more
      extensive congenital damages that would suggest the restrictive terminology. That
      prompts to assess cautiously prenatal diagnosis of NTD, and to get detailed
      pathological examination after termination of pregnancy.

PMID- 17554801
TI  - Cell-free mRNA concentrations of CRH, PLAC1, and selectin-P are increased in the
      plasma of pregnant women with preeclampsia.
AB  - OBJECTIVE: To compare mRNA concentrations of corticotrophin-releasing hormone
      (CRH), placenta specific-1 (PLAC1), and selectin-P in preeclamptic and normal
      pregnancies. METHODS: Peripheral blood samples were obtained from 43 pregnant
      women with preeclampsia and 41 control subjects. Plasma was harvested from
      samples and RNA extracted. Plasma RNA was analyzed using reverse transcription
      polymerase chain reaction (PCR) assay. Median concentrations of CRH, PLAC1, and
      selectin-P mRNA in plasma were compared, to assess possible differences in
      distribution. Data were also stratified and compared according to clinical
      severity of preeclampsia. Finally, CRH, PLAC1, and selectin-P were plotted
      against quantitative distributions of blood pressure and proteinuria. RESULTS:
      All markers were differently distributed between cases and controls. Median
      values in subgroups correlated with severity of preeclampsia. All markers
      correlated with both. Selectin-P was identified as the marker with the highest
      degree of correlation. No correlation was found between any markers in the
      control group and proteinuria or blood pressure. CONCLUSION: CRH, PLAC1, and
      selectin-P are distributed differently in preeclampsia cases compared to controls
      and correlate with signs of preeclampsia.

PMID- 17554802
TI  - Parental mosaic trisomy 21 detected following maternal cell contamination of an
      amniotic fluid specimen from a normal male pregnancy.
AB  - We report a case of maternal mosaic trisomy 21 ascertained at prenatal diagnosis
      as a result of maternal cell contamination of an amniotic fluid sample. A 34 year
      old female was referred for karyotyping because of a previous trisomy 21
      pregnancy. Chromosome analysis of primary in situ cultures showed a karyotype of
      47,XX, + 21[6]/46,XY[32]/46,XX[2]. Molecular testing demonstrated maternal cell
      contamination of the amniotic fluid sample and G-banded karyotyping of maternal
      blood showed that 3/200 cells had trisomy 21, consistent with the mother being a
      Down syndrome mosaic. A normal male baby with a 46,XY chromosome complement was
      delivered at 30 weeks. This case emphasises the need for close collaboration
      between cytogenetic and molecular genetics laboratories in resolving unusual
      cases of mosaicism.

PMID- 17554803
TI  - Maternal serum free beta-hCG and PAPP-A in patients with habitual abortion
      influence on first-trimester screening for chromosomal abnormalities.
AB  - OBJECTIVE: To explore if maternal serum free beta-hCG and pregnancy-associated
      plasma protein A (PAPP-A) levels in the first-trimester of pregnancy are altered
      in patients with habitual abortions and if there is an effect on first-trimester
      screening for Down syndrome. METHODS: A retrospective study was conducted on 913
      normal singleton fetuses that underwent first-trimester combined screening for
      Down syndrome. Maternal serum PAPP-A and free beta-hCG were compared between
      patients with (n = 64) and without habitual abortions (n = 849). RESULTS: The
      medians +/- SD log(10) MoM of PAPP-A and free beta-hCG +/- SD in patients with
      and without habitual abortions were 0.063 +/- 0.28 versus - 0.014 +/- 0.27 and -
      0.001 +/- 0.27 versus - 0.018 +/- 0.31, with a p value of 0.042 and 0.87,
      respectively. The screen positive rate setting the cut off at 1:350 looking at
      the background risk for trisomy 21 was 71.4% in women with and 81.2% in women
      without habitual abortion, after combined first-trimester screening it was 7.8%
      in women with and 10.1% in women without recurrent abortion. CONCLUSIONS:
      Patients with habitual abortions have slightly increased maternal serum PAPP-A
      levels in the first-trimester. This marginal difference seems not to effect risk
      calculation in combined first-trimester screening for trisomy 21.

PMID- 17554804
TI  - Synthesis and characterization of succinylcholine-d18 and succinylmonocholine-d3
      designed for simultaneous use as internal standards in mass spectrometric
      analyses.
AB  - Succinylcholine (SUX) is a routinely used yet potentially lethal depolarizing
      muscle relaxant, the detection of which poses severe problems to the clinical or
      forensic analyst: within a few minutes after its in vivo administration, SUX is
      broken down via succinylmonocholine (SMC) to yield the endogenous substances
      succinic acid and choline. For quantification of SUX and SMC in biological
      matrices using mass spectrometric detection, appropriate internal standards, i.e.
      deuterated analogs of the above substances, are indispensable but not
      commercially available. Internal standards for both substances were hence
      tailored to fit the analytical needs. The two-step synthesis and subsequent
      characterization of SUX-d(18) and SMC-d(3) using a combination of nuclear
      magnetic resonance (NMR) spectroscopy, fast atom bombardment mass spectroscopy
      (FAB-MS) and high-performance liquid chromatography/tandem mass spectrometry
      (HPLC-MS/MS) are described. SUX-d(18) was synthesized by reacting ethanolamine
      and iodomethane-d(3) in a first quaternization step to choline-d(9), which in
      turn was esterified with succinyldichloride to yield the final product. SMC-d(3)
      was produced by esterification of succinic acid anhydride with
      dimethylaminoethanol, yielding desmethyl-SMC as intermediate product. The latter
      was then reacted with iodomethane-d(3) to obtain SMC-d(3). (1)H- and (13)C-NMR
      data support the identity and purity as well as the designated deuteration of
      both preparations, findings which were further confirmed by FAB-MS as well as
      HPLC-MS/MS. Owing to a thoughtful design, the obtained substances SUX-d(18) and
      SMC-d(3) feature different deuteration patterns at their trimethylamine moieties,
      and thus finally offer the possibility to simultaneously quantify SUX and SMC in
      clinical as well as forensic samples using isotope dilution mass spectrometry.

PMID- 17554805
TI  - Solid-phase peptide synthesis using nanoparticulate amino acids in water.
AB  - Solid-phase peptide synthesis has many advantages compared with solution peptide
      synthesis. However, this procedure requires a large amount of organic solvents.
      Since safe organic solvent waste disposal is an important environmental problem,
      a technology based on coupling reaction of suspended nanoparticle reactants in
      water was studied. Fmoc-amino acids are used widely, but most of them show low
      solubility in water. We prepared well-dispersible Fmoc-amino acid nanoparticles
      in water by pulverization using a planetary ball mill in the presence of
      poly(ethylene glycol). Leu-enkephalin amide was prepared successfully using the
      nanoparticulate Fmoc-amino acid on a poly(ethylene glycol)-grafted Rink amide
      resin in water.

PMID- 17554806
TI  - The Nobel trail of Vincent du Vigneaud.
AB  - The Nobel Prize for chemistry of 1955 was awarded to Vincent du Vigneaud. After a
      brief outline of his career and accomplishments, some archive material related to
      this decision of the Royal Swedish Academy of Sciences is presented. Other
      archive studies have shown that du Vigneaud was also considered for the
      corresponding prize in physiology or medicine.

PMID- 17554807
TI  - Transport of a tripeptide, Gly-Pro-Hyp, across the porcine intestinal brush
      border membrane.
AB  - The transcellular transport of oligopeptides across intestinal epithelial cells
      has attracted considerable interest in investigations into how biologically
      active peptides express diverse physiological functions in the body. It has been
      postulated that the tripeptide, Gly-Pro-Hyp, which is frequently found in
      collagen sequences, exhibits bioactivity. However, the mechanism of uptake of
      dietary di- and tripeptides by intestinal epithelial cells is not well
      understood. In this study, we used porcine brush-border membrane (BBM) vesicles
      to assess Gly-Pro-Hyp uptake, because these vesicles can structurally and
      functionally mimic in vivo conditions of human intestinal apical membranes. The
      present study demonstrated the time-dependent degradation of this tripeptide into
      the free-form Gly and a dipeptide, Pro-Hyp, on the apical side of the BBM
      vesicles. In parallel with the hydrolysis of the tripeptide, the dipeptide Pro
      Hyp was identified in the BBM intravesicular space environment. We found that the
      transcellular transport of Pro-Hyp across the BBM was inhibited by the addition
      of a competitive substrate (Gly-Pro) for peptide transporter (PEPT1) and was pH
      dependent. These results indicate that Gly-Pro-Hyp can be partially hydrolyzed by
      the brush-border membrane-bound aminopeptidase N to remove Gly, and that the
      resulting Pro-Hyp is, in part, transported into the small intestinal epithelial
      cells via the H+-coupled PEPT1. Gly-Pro-Hyp cannot cross the epithelial apical
      membrane in an intact form, and Pro-Hyp is highly resistant to hydrolysis by
      intestinal mucosal apical proteases.

PMID- 17554808
TI  - Multimer formation by FKBP-12: roles for cysteine 23 and phenylalanine 36.
AB  - FKBP-12 mediates the immunosuppressive actions of FK506 and rapamycin, and
      modulates the activities of the ryanodine, IP3 and type 1 TGF-ss receptors.
      Additionally, FKBP-12 possesses cis-trans peptidylprolyl isomerase (rotamase)
      activity. We have discovered that recombinant FKBP-12 readily forms a dimer and a
      small amount of trimer under nonreducing conditions. A mutant with substitution
      at the sole cysteine residue of FKBP-12 (C23S) did not form dimers or trimers.
      Using mutants with 5% or less rotamase activity, the formation of dimers was
      independent of enzymatic activity. The formation of trimers was abrogated by a
      F36Y substitution, even though dimer formation was preserved. Dimers were also
      observed with native FKBP-12 that was detached from rabbit skeletal muscle
      ryanodine receptors using FK590. The multimers of FKBP-12 could interact with
      molecular targets distinctly from the FKBP-12 monomer, for example, by
      facilitating the assembly of multimeric receptors or coordinating the activity of
      receptor subunits.

PMID- 17554809
TI  - Structure analysis of triterpene saponins in Polygala tenuifolia by electrospray
      ionization ion trap multiple-stage mass spectrometry.
AB  - Eighteen different triterpene saponins isolated from Polygala tenuifolia were
      investigated by electrospray ionization ion trap multiple-stage mass spectrometry
      (ESI-ITMS(n)) in positive and negative ion modes. MS(1)-MS(3)/MS(4) spectra of
      the both modes were analyzed, and they all gave fragments in line and shared
      common fragmentation patterns. Key fragments from MS(n) spectra of both the modes
      and their proposed fragmentation pathways were constructed with examples
      illustrated for the formation of characteristic fragments in the saponins. Two
      special fragmentation patterns were proposed: (1) the formation of fragments by
      cleavage of CH(2)O from Delta(12)-14alpha-CH(2)OH of the oleanene-type saponin
      aglycone in both positive and negative MS(n) (n > or = 2) modes; (2) the
      occurrence of fragments by cleavage of CO(2) and 3-glucose as the characteristic
      structure feature of 23-COOH at the oleanene-type saponin aglycones coupled with
      3-Glc substitutes in the negative MS(n) (n > or = 2) modes. Peak intensities in
      MS(n) spectra were also correlated with structural features and fragmentation
      preferences of the investigated saponins, which are discussed in detail. In
      general, fragments formed predominantly by cleavages of glycosidic bonds in the
      positive mode, while selective cleavages of acyl bonds preceded that of
      glycosidic bonds in negative MS(n) (n > or = 2) mode, both of which could well be
      applied to the structural analysis of these saponins. Interpretation of MS(n)
      spectra presented here provided diagnostic key fragment ions important for the
      structural elucidation of saponins in P.tenuifolia.

PMID- 17554810
TI  - Robotic telesurgery: a real-world comparison of ground- and satellite-based
      internet performance.
AB  - BACKGROUND: Telesurgery was performed with ground vs. satellite networks, and
      differing satellite bandwidths. METHODS: The networks were compared during
      internal mammary artery (LIMA) dissection in pigs (n = 8). Length of LIMA
      dissected and surgical quality (five-point scale) were recorded. Also, satellite
      bandwidth was decreased (n = 7) to determine a limit for telesurgery. RESULTS: No
      significant differences existed in LIMA dissection during the ground (4.3 +/- 0.5
      cm) and satellite phases (5.4 +/- 1.1 cm; p > 0.05) or in quality of surgery,
      although latency on satellite was 10 times greater (55 vs. 600 ms). With
      decreasing satellite bandwidth, surgery was not possible below 3 Mb/s, and
      quality of surgery was significantly decreased comparing 9 Mb/s (4.38 +/- 0.66/5)
      to 3 Mb/s (4.10 +/- 0.80/5; p < 0.05). CONCLUSIONS: Satellite communication is a
      viable telesurgical modality. Satellite bandwidth should be above 5 Mb/s during
      telesurgery if used primarily or as back-up.

PMID- 17554811
TI  - Gates of opportunity.

PMID- 17554812
TI  - Northern exposure for EMBL.

PMID- 17554813
TI  - The mandate of innovation management.

PMID- 17554814
TI  - Novel hantavirus sequences in Shrew, Guinea.

PMID- 17554815
TI  - Sense and sensibility in neuroengineering.

PMID- 17554816
TI  - The surprising performance of present-day cochlear implants.
AB  - The speech reception performance of a recipient of the Clarion CII implant was
      evaluated with a comprehensive set of tests. The same tests were administered for
      a group of six subjects with normal hearing. Scores for the implant subject were
      not different from the scores for the normal-hearing subjects, for seven of the
      nine tests, including the most difficult test used in standard clinical practice.
      These results are both surprising and encouraging, in that the implant provides
      only a very crude mimicking of only some aspects of the normal physiology.

PMID- 17554817
TI  - Design for a simplified cochlear implant system.
AB  - A simplified cochlear implant (CI) system would be appropriate for widespread use
      in developing countries. Here, we describe a CI that we have designed to realize
      such a concept. The system implements 8 channels of processing and stimulation
      using the continuous interleaved sampling (CIS) strategy. A generic digital
      signal processing (DSP) chip is used for the processing, and the filtering
      functions are performed with a fast Fourier transform (FFT) of a microphone or
      other input. Data derived from the processing are transmitted through an
      inductive link using pulse width modulation (PWM) encoding and amplitude shift
      keying (ASK) modulation. The same link is used in the reverse direction for
      backward telemetry of electrode and system information. A custom receiver
      stimulator chip has been developed that demodulates incoming data using pulse
      counting and produces charge balanced biphasic pulses at 1000 pulses/s/electrode.
      This chip is encased in a titanium package that is hermetically sealed using a
      simple but effective method. A low cost metal-silicon hybrid mold has been
      developed for fabricating an intracochlear electrode array with 16 ball-shaped
      stimulating contacts.

PMID- 17554818
TI  - An optically powered single-channel stimulation implant as test system for
      chronic biocompatibility and biostability of miniaturized retinal vision
      prostheses.
AB  - A microsystem based microimplant with an optically powered single-channel
      stimulator was designed and developed as test system for an epi-retinal vision
      implant. Biostability of the hybrid assembly and the encapsulation materials were
      evaluated in pilot experiments in chronic implantations in a cat animal model.
      The implant was fabricated on a flexible polyimide substrate with integrated
      platinum electrode, interconnection lines, and contact pads for hybrid
      integration of electronic components. The receiver part was realized with four
      photodiodes connected in series. A parylene C coating was deposited on the
      electronic components as insulation layer. Silicone rubber was used to
      encapsulate the electronics in the shape of an artificial intraocular lens to
      allow proper implantation in the eye. Pilot experiments showed the biostability
      of the encapsulation approach and full electric functionality of the microimplant
      to generate stimulation currents over the implantation period of three months in
      two cats. In one cat, electrical stimulation of the retina evoked neuronal
      responses in the visual cortex and indicated the feasibility of the system
      approach for chronic use.

PMID- 17554819
TI  - Image processing for a high-resolution optoelectronic retinal prosthesis.
AB  - In an effort to restore visual perception in retinal diseases such as age-related
      macular degeneration or retinitis pigmentosa, a design was recently presented for
      a high-resolution optoelectronic retinal prosthesis having thousands of
      electrodes. This system requires real-time image processing fast enough to
      convert a video stream of images into electrical stimulus patterns that can be
      properly interpreted by the brain. Here, we present image-processing and tracking
      algorithms for a subretinal implant designed to stimulate the second neuron in
      the visual pathway, bypassing the degenerated first synaptic layer. For this
      task, we have developed and implemented: 1) A tracking algorithm that determines
      the implant's position in each frame. 2) Image cropping outside of the implant
      boundaries. 3) A geometrical transformation that distorts the image appropriate
      to the geometry of the fovea. 4) Spatio-temporal image filtering to reproduce the
      visual processing normally occurring in photoceptors and at the photoreceptor
      bipolar cell synapse. 5) Conversion of the filtered visual information into a
      pattern of electrical current. Methods to accelerate real-time transformations
      include the exploitation of data redundancy in the time domain, and the use of
      precomputed lookup tables that are adjustable to retinal physiology and allow
      flexible control of stimulation parameters. A software implementation of these
      algorithms processes natural visual scenes with sufficient speed for real-time
      operation. This computationally efficient algorithm resembles, in some aspects,
      biological strategies of efficient coding in the retina and could provide a
      refresh rate higher than fifty frames per second on our system.

PMID- 17554820
TI  - Chronic vestibulo-ocular reflexes evoked by a vestibular prosthesis.
AB  - We are developing prosthetics for patients suffering from peripheral vestibular
      dysfunction. We tested a sensory-replacement prosthesis that stimulates neurons
      innervating the vestibular system by providing chronic pulsatile stimulation to
      electrodes placed in monkeys' lateral semicircular canals, which were plugged
      bilaterally, and used head angular velocity to modulate the current pulse rate.
      As an encouraging finding, we observed vestibulo-ocular reflexes that continued
      to be evoked by the motion-modulated stimulation months after the nystagmus
      evoked by the constant-rate baseline stimulation had dissipated. This suggests
      that long-term functional replacement of absent vestibular function is feasible.

PMID- 17554821
TI  - A multichannel semicircular canal neural prosthesis using electrical stimulation
      to restore 3-d vestibular sensation.
AB  - Bilateral loss of vestibular sensation can be disabling. Those afflicted suffer
      illusory visual field movement during head movements, chronic disequilibrium and
      postural instability due to failure of vestibulo-ocular and vestibulo-spinal
      reflexes. A neural prosthesis that emulates the normal transduction of head
      rotation by semicircular canals could significantly improve quality of life for
      these patients. Like the three semicircular canals in a normal ear, such a device
      should at least transduce three orthogonal (or linearly separable) components of
      head rotation into activity on corresponding ampullary branches of the vestibular
      nerve. We describe the design, circuit performance and in vivo application of a
      head-mounted, semi-implantable multichannel vestibular prosthesis that encodes
      head movement in three dimensions as pulse-frequency-modulated electrical
      stimulation of three or more ampullary nerves. In chinchillas treated with
      intratympanic gentamicin to ablate vestibular sensation bilaterally, prosthetic
      stimuli elicited a partly compensatory angular vestibulo-ocular reflex in
      multiple planes. Minimizing misalignment between the axis of eye and head
      rotation, apparently caused by current spread beyond each electrode's targeted
      nerve branch, emerged as a key challenge. Increasing stimulation selectivity via
      improvements in electrode design, surgical technique and stimulus protocol will
      likely be required to restore AVOR function over the full range of normal
      behavior.

PMID- 17554822
TI  - Development of a BIONic muscle spindle for prosthetic proprioception.
AB  - The replacement of proprioceptive function, whether for conscious sensation or
      feedback control, is likely to be an important aspect of neural prosthetic
      restoration of limb movements. Thus far, however, it has been hampered by the
      absence of unobtrusive sensors. We propose a method whereby fully implanted,
      telemetrically operated BIONs monitor muscle movement, and thereby detect changes
      in joint angle(s) and/or limb posture without requiring the use of secondary
      components attached to limb segments or external reference frames. The sensor
      system is designed to detect variations in the electrical coupling between
      devices implanted in neighboring muscles that result from changes in their
      relative position as the muscles contract and stretch with joint motion. The goal
      of this study was to develop and empirically validate mathematical models of the
      sensing scheme and to use computer simulations to provide an early proof of
      concept and inform design of the overall sensor system. Results from experiments
      using paired dipoles in a saline bath and finite element simulations have given
      insight into the current distribution and potential gradients exhibited within
      bounded anisotropic environments similar to a human limb segment and demonstrated
      an anticipated signal to noise ratio of at least 8:1 for submillimeter resolution
      of relative implant movement over a range of implant displacements up to 15 cm.

PMID- 17554823
TI  - Performance of multisite silicon microprobes implanted chronically in the ventral
      cochlear nucleus of the cat.
AB  - A central auditory prosthesis based on microstimulation within the ventral
      cochlear nucleus (VCN) offers a means of restoring hearing to persons whose
      auditory nerve has been destroyed bilaterally and cannot benefit from cochlear
      implants. Arrays of silicon probes with 16 stimulating sites were implanted into
      the VCN of adult cats, for up to 314 days. Compound neuronal responses evoked
      from the sites in the VCN were recorded periodically in the central nucleus of
      the contralateral inferior colliculus (ICC). The threshold and growth of most of
      the responses were stable for at least 250 days after implantation of the arrays.
      The responses evoked from the deepest and shallowest electrode sites did exhibit
      some changes over time but none of the thresholds exceeded 10 microA. The
      thresholds and growth of the compound responses from most of the stimulating
      sites were very stable over time, and comparable to those of chronically
      implanted single-site iridium microelectrodes. Multiunit neuronal activity evoked
      from the stimulating sites in the VCN was recorded along the dorsolateral
      ventromedial (DLVM) axis of the ICC. The distribution, span and degree of overlap
      of the multiunit activity demonstrated the utility of the multisite, multishank
      array configuration as a means of accessing the neuronal populations in the VCN
      that encode various acoustic frequencies. These findings are encouraging for the
      prospects of developing an auditory prosthesis employing multi-site silicon
      microprobes.

PMID- 17554824
TI  - Nonlinear dynamic modeling of spike train transformations for hippocampal
      cortical prostheses.
AB  - One of the fundamental principles of cortical brain regions, including the
      hippocampus, is that information is represented in the ensemble firing of
      populations of neurons, i.e., spatio-temporal patterns of electrophysiological
      activity. The hippocampus has long been known to be responsible for the formation
      of declarative, or fact-based, memories. Damage to the hippocampus disrupts the
      propagation of spatio-temporal patterns of activity through hippocampal internal
      circuitry, resulting in a severe anterograde amnesia. Developing a neural
      prosthesis for the damaged hippocampus requires restoring this multiple-input,
      multiple-output transformation of spatio-temporal patterns of activity. Because
      the mechanisms underlying synaptic transmission and generation of electrical
      activity in neurons are inherently nonlinear, any such prosthesis must be based
      on a nonlinear multiple-input, multiple-output model. In this paper, we have
      formulated the transformational process of multi-site propagation of spike
      activity between two subregions of the hippocampus (CA3 and CA1) as the
      identification of a multiple-input, multiple-output (MIMO) system, and proposed
      that it can be decomposed into a series of multiple-input, single-output (MISO)
      systems. Each MISO system is modeled as a physiologically plausible structure
      that consists of 1) linear/nonlinear feedforward Volterra kernels modeling
      synaptic transmission and dendritic integration, 2) a linear feedback Volterra
      kernel modeling spike-triggered after-potentials, 3) a threshold for spike
      generation, 4) a summation process for somatic integration, and 5) a noise term
      representing intrinsic neuronal noise and the contributions of unobserved inputs.
      Input and output spike trains were recorded from hippocampal CA3 and CA1 regions
      of rats performing a spatial delayed-nonmatch-to-sample memory task that requires
      normal hippocampal function. Kernels were expanded with Laguerre basis functions
      and estimated using a maximum-likelihood method. Complexity of the feedforward
      kernel was progressively increased to capture higher-order system nonlinear
      dynamics. Results showed higher prediction accuracies as kernel complexity
      increased. Self-kernels describe the nonlinearities within each input. Cross
      kernels capture the nonlinear interaction between inputs. Second- and third-order
      nonlinear models were found to successfully predict the CA1 output spike
      distribution based on CA3 input spike trains. First-order, linear models were
      shown to be insufficient.

PMID- 17554825
TI  - Passive neutralization of myoelectric interference from neural recording
      tripoles.
AB  - In this paper, we present a simple passive technique for removing myoelectric
      interference in neural recording systems using tripolar electrodes. Imbalance is
      simply unavoidable with the conventional quasi-tripole (QT) amplifier and this
      technakshnique is based on a modified version of the QT, which sees the tripole
      as a bridge that can be balanced by adding impedance to one of the outer
      electrodes. We show that parallel resistance and capacitance is better than a
      series combination for use at all frequencies, and that with a tripole that was
      intentionally made imbalanced, by an amount that we measure as 3%, the
      interference can be reduced about 10-fold. It is important to null the
      interference at low frequencies, in the electromyography (EMG) band, to get the
      best improvement. Common-mode interference can also be reduced by appropriate
      trimming if necessary.

PMID- 17554826
TI  - A fully integrated mixed-signal neural processor for implantable multichannel
      cortical recording.
AB  - A 64-channel neural processor has been developed for use in an implantable neural
      recording microsystem. In the Scan Mode, the processor is capable of detecting
      neural spikes by programmable positive, negative, or window thresholding. Spikes
      are tagged with their associated channel addresses and formed into 18-bit data
      words that are sent serially to the external host. In the Monitor Mode, two
      channels can be selected and viewed at high resolution for studies where the
      entire signal is of interest. The processor runs from a 3-V supply and a 2-MHz
      clock, with a channel scan rate of 64 kS/s and an output bit rate of 2 Mbps.

PMID- 17554827
TI  - A benchtop system to assess cortical neural interface micromechanics.
AB  - A benchtop brain tissue-microelectrode insertion model system was developed to
      aid in improving the design of cortical neural interfaces. The model partially
      mimics the in vivo environment via the use of human cadaver brain specimens
      (nspecimen = 6), or agar gel exposed to physiologically relevant mechanical
      oscillations. 150 lpm diameter stainless-steel microelectrode wires (TS = 600
      MPa) implanted 3.0 cm within fixed human primary auditory cortex (ntrial > 10)
      experienced 133 +/- 8 and 64 +/- 4 mN of peak and steady axial forces. When
      subjected to a 3 Hz, 3-mm vertical oscillation, dynamic force amplitudes (ntrial
      > 10) of 148 +/- 10 mN were measured. The model system allows the study and
      comparison of static and dynamic forces and their mechanical influences on
      proposed implanted microelectrode structures.

PMID- 17554828
TI  - Extraction force and cortical tissue reaction of silicon microelectrode arrays
      implanted in the rat brain.
AB  - Micromotion of implanted silicon multielectrode arrays (Si MEAs) is thought to
      influence the inflammatory response they elicit. The degree of strain that
      micromotion imparts on surrounding tissue is related to the extent of mechanical
      integration of the implanted electrodes with the brain. In this study, we
      quantified the force of extraction of implanted four shank Michigan electrodes in
      adult rat brains and investigated potential cellular and extracellular matrix
      contributors to tissue-electrode adhesion using immunohistochemical markers for
      microglia, astrocytes and extracellular matrix deposition in the immediate
      vicinity of the electrodes. Our results suggest that the peak extraction force of
      the implanted electrodes increases significantly from the day of implantation
      (day 0) to the day of extraction (day 7 and day 28 postimplantation) (1.68 +/-
      0.54 g, 3.99 +/- 1.31 g, and 4.86 +/- 1.49 g, respectively; mean +/- SD; n = 4).
      For an additional group of four shank electrode implants with a closer intershank
      spacing we observed a significant increase in peak extraction force on day 28
      postimplantation compared to day 0 and day 7 postimplantation (5.56 +/- 0.76 g,
      0.37 +/- 0.12 g and 1.87 +/- 0.88 g, respectively; n = 4). Significantly, only
      glial fibrillary acidic protein (GFAP) expression was correlated with peak
      extraction force in both electrode designs of all the markers of astroglial scar
      studied. For studies that try to model micromotion-induced strain, our data
      implies that adhesion between tissue and electrode increases after implantation
      and sheds light on the nature of implanted electrode-elicited brain tissue
      reaction.

PMID- 17554829
TI  - Optical parameter variability in laser nerve stimulation: a study of pulse
      duration, repetition rate, and wavelength.
AB  - Pulsed lasers can evoke neural activity from motor as well as sensory neurons in
      vivo. Lasers allow more selective spatial resolution of stimulation than the
      conventional electrical stimulation. To date, few studies have examined pulsed,
      mid-infrared laser stimulation of nerves and very little of the available optical
      parameter space has been studied. In this study, a pulsed diode laser, with
      wavelength between 1.844-1.873 microm, was used to elicit compound action
      potentials (CAPs) from the auditory system of the gerbil. We found that pulse
      durations as short as 35 micros elicit a CAP from the cochlea. In addition,
      repetition rates up to 13 Hz can continually stimulate cochlear spiral ganglion
      cells for extended periods of time. Varying the wavelength and, therefore, the
      optical penetration depth, allowed different populations of neurons to be
      stimulated. The technology of optical stimulation could significantly improve
      cochlear implants, which are hampered by a lack of spatial selectivity.

PMID- 17554830
TI  - Shape memory alloy microactuation of tf-lIFes: preliminary results.
AB  - In this paper, a new approach aimed at improving the performance of intraneural
      longitudinal interfaces (tf-LIFEs) with the peripheral nervous system (PNS) is
      presented. Our goal is to develop a movable interface by embedding microactuators
      into the flexible tf-LIFEs structure. In this way, the optimal position of the
      electrical contacts can be searched inside the PNS and lost connections with
      neural cells could be replaced. For this purpose a thin film of shape memory
      alloy (tf-SMA) was selected. A multisegmented SMA was realized and embedded
      between two polyimide thin films in order to simulate the tf-LIFE structure.
      Thermal evaluation, fabrication procedure, the first characterization and
      preliminary experimental results of the new movable interface are described in
      the manuscript. A total controllable stroke of about 10 microm was obtained for
      the presented prototype.

PMID- 17554831
TI  - Vertically aligned carbon nanofiber architecture as a multifunctional 3-D neural
      electrical interface.
AB  - Developing biomaterial constructs that closely mimic the natural tissue
      microenvironment with its complex chemical and physical cues is essential for
      improving the function and reliability of implantable devices, especially those
      that require direct neural-electrical interfaces. Here we demonstrate that free
      standing vertically aligned carbon nanofiber (VACNF) arrays can be used as a
      multifunctional 3-D brush-like nanoengineered matrix that interpenetrates the
      neuronal network of PC12 cells. We found that PC12 neuron cells cultured on VACNF
      substrates can form extended neural network upon proper chemical and biochemical
      modifications. The soft 3-D VACNF architecture provides a new platform to fine
      tune the topographical, mechanical, chemical, and electrical cues at subcellular
      nanoscale. This new biomaterial platform can be used for both fundamental studies
      of material-cell interactions and the development of chronically stable
      implantable neural devices. Micropatterned multiplex VACNF arrays can be
      selectively controlled by electrical and electrochemical methods to provide
      localized stimulation with extraordinary spatiotemporal resolution. Further
      development of this technology may potentially result in a highly multiplex
      closed-loop system with multifunctions for neuromodulation and neuroprostheses.

PMID- 17554833
TI  - Patient care: a commodity or an obligation.

PMID- 17554834
TI  - LPN scope of practice case study.

PMID- 17554832
TI  - Neurobiological assessment of regenerative electrodes for bidirectional
      interfacing injured peripheral nerves.
AB  - Regenerative electrodes are designed to interface regenerated axons from a
      sectioned peripheral nerve. Applicability of regenerative electrodes depends on
      biocompatibility, success of axonal regeneration, secondary nerve damage, and
      adequacy of interface electronics. Polyimide sieve electrodes with 281 holes were
      chronically implanted in the severed sciatic nerve of 30 rats. Regeneration was
      successful in all the animals, with increasing numbers of regenerated myelinated
      fibers from 2 to 6 mo. However, constrictive axonopathy affected a few cases from
      6 to 12 mo. postimplantation. A second electrode design with 571 holes and 27
      ring electrodes was developed. The number of regenerated axons increased thanks
      to the larger open area. Recordings were obtained from a low proportion of
      electrodes on the sieve in response to distal stimulation. Difficulties for
      recording impulses with regenerative electrodes include the small size of
      regenerated axons, changes in membrane excitability and in target reconnection.

PMID- 17554835
TI  - [Evaluation and care of pain in the aged person].

PMID- 17554836
TI  - A re-examination of cultural factors that mitigate risk and promote resilience in
      relation to African American suicide: a review of the literature and
      recommendations for future research.
AB  - Suicide among African Americans has been acknowledged by the U.S. Surgeon General
      as a growing crisis. However, suicide remains understudied in this population. In
      this article, the authors examine the literature related to cultural protective
      factors that buffer African Americans from suicide risk. They present an overview
      of suicide among African Americans, review the culture and world-view of African
      Americans, and examine the degree to which these cultural variables protect
      against suicide risk. Finally, they discuss the limitations of the extant
      research on African American suicide, set an agenda for future research, and
      discuss its implications for clinical practice and public policy.

PMID- 17554837
TI  - Suicide among Asian Americans: what do we know? What do we need to know?
AB  - The current review begins with an acknowledgment of the diversity within the
      Asian American population as well as the scarcity of information on suicide among
      this particular racial/ethnic minority group. In analyzing what is known and what
      still needs to be learned about suicide among Asian Americans, the current
      article provides a critical review of significant factors such as age, gender,
      religious and spirituality issues, acculturation, social support, familial
      dynamics, social integration as well as gay/lesbian/bisexual orientations. In
      examining these factors, recommendations related to interventions and the
      existing research gaps are also discussed.

PMID- 17554838
TI  - Suicide behavior among Latino and Latina adolescents: conceptual and
      methodological issues.
AB  - Suicide is the cause of 11.7% of all deaths among youth and young adults aged 10
      to 24 years in the United States (J. A. Grunbaum et al., 2004). Suicide is third
      leading cause of death for young Latinos/as aged 10 to 24 years (National
      Institute of Mental Health, 2001). Latino/a youth are at a greater risk of
      suicide behavior than other ethnic groups (G. Canino & R. E. Roberts, 2001).
      Latinos/as have less access to mental health services than do Whites and are less
      likely to receive needed care (U.S. Department of Health and Human Services,
      2001). This article reviews the scientific literature related to suicide behavior
      among Latino/a adolescent since 1990. Conceptual and methodological issues in
      research are examined and the role of contextual and developmental factors on
      suicide behavior is discussed. The empirical findings of comparative ethnic
      minority studies, studies focused on Latino/a youth, and within-group studies are
      reviewed. Research on Latino/a adolescent suicide behavior is limited, few
      studies focus on any Latino subgroup and it is rare to find comparative studies
      focus on within-group diversity among Latinos. For the most part, no explanatory
      variables that may account for the differences among groups or that help explain
      the meaning of the suicide behavior were found. Research efforts should move away
      from using generic labels (e.g., Hispanics, Latinos, etc.) and shift toward
      addressing group-specific (e.g., Mexican Americans, Puerto Ricans, etc.) findings
      that have implications for prevention and treatment of target populations (G.
      Canino & R. E. Roberts, 2001; J. D. Hovey & C. A. King, 1997). Suicide behavior
      studies among specific Latino/a adolescents that are based on theory and informed
      by ecodevelopmental, gender-specific perspectives should advance the field.

PMID- 17554839
TI  - Reviewing suicide in Native American communities: situating risk and protective
      factors within a transactional-ecological framework.
AB  - The alarming prevalence of suicidal behaviors in Native American communities
      remains a major concern in the 21st-century United States. Recent reviews have
      demonstrated that prevention programs and intervention efforts using
      transactional-ecological models have effectively reduced suicidal behaviors in
      the American Indian and Alaska Native populations sampled. As a result, this
      article adopts a transactional-ecological framework for conceptualizing
      suicidality and identifying points of intervention. Drawing on the most current
      empirical reports, the epidemiology of Native American suicidal behaviors is
      reviewed, while situating risk and protective factors within a biopsychosocial
      framework. Opportunities for intervention are discussed with a focus on the
      interactions between individuals and their environments, and the antecedent
      conditions leading to zones of heightened suicide risk.

PMID- 17554840
TI  - Suicide and suicidal-related behaviors among indigenous Pacific Islanders in the
      United States.
AB  - The authors present a comprehensive review on U.S. Pacific Islander suicide and
      suicide-related behaviors to extend the knowledge and understanding of suicide
      and suicide-related behaviors among the indigenous peoples of the state of
      Hawai'i, the territories of American Samoa, Guam, Commonwealth of the Northern
      Mariana Islands, and the Pacific Island Nations of Micronesia (Federated States
      of Micronesia, the Republic of Belau [Palau], and the Republic of the Marshall
      Islands). Historical, geographic, epidemiological, social, and cultural
      information is presented on these Pacific Island populations. Suicide behavioral
      data are presented for Pacific Islanders living within the U.S. and affiliated
      Pacific territories and nations from the existing scientific literature along
      with archival data and 2 epidemiological studies that assess suicidal behaviors
      and related psychosocial factors and measures of psychopathology among large
      community samples of youth in Hawai'i. The authors describe common patterns and
      differences among these populations, along with social-cultural practices that
      may explain suicide phenomenology among these U.S. indigenous peoples who--while
      small in numbers when compared with the total U.S. population--possess striking
      health disparities when compared to other populations within the U.S. and in
      their island homelands.

PMID- 17554841
TI  - Who should determine what is best for children in state custody who object to
      psychotropic medication?
AB  - This article explores a child's right to refuse medical treatment, in contrast to
      giving the state or the parents this choice. The article specifically explores a
      child's right to refuse psychotropic drugs, which are more limiting of personal
      liberty than physical restraints and can have long-lasting side effects. With a
      focus on children's competence and the significant side effects of psychotropic
      drugs, the author concludes that caseworkers do not know the best interests of
      children in state custody and thus adolescents should be allowed to make their
      own decisions about psychotropic medications.

PMID- 17554842
TI  - Greenberg v. Miami Children 's Hospital: unjust enrichment and the patenting of
      human genetic material.
AB  - Individuals and societal groups are questioning the practice of patenting human
      genetic material in the context of medical research and health care, where
      diverse ethical, social, and political objections are being raised by critics. A
      recent case provides a broad legal theory, the common law cause of action, unjust
      enrichment, and a precedent for challenging the commercialization and patenting
      of human genetic material.

PMID- 17554843
TI  - Moral hazard in health insurance: are consumer-directed plans the answer?
AB  - The concept of moral hazard in relation to health insurance is an area that has
      both haunted and fascinated economists, policy-makers, and payers almost since
      the first health insurance plans were offered by employers. Through the years
      since Kenneth Arrow's groundbreaking work in 1963, the health care industry has
      been looking for the proper level of cost-share for patient insureds that will
      affect their health care choices. The approach of some newer plan offerings,
      termed 'consumer-directed' or 'consumer-driven' plans by their promoters, seem to
      have the potential of affecting moral hazard in health insurance.

PMID- 17554844
TI  - Reconceptualizing elder abuse: treating the disease of senior community
      exclusion.
AB  - This article focuses on the phenomenon of elder abuse, which is one of the
      paramount symptoms of the larger community's failure to address the social,
      medical, and legal needs of the senior populace. Although there have been
      multidisciplinary efforts to address this problem, they are not responsive to the
      needs of the senior population itself In response, the authors propose a model
      that takes into account the specific concerns of local senior communities and
      provides seniors and their stakeholder providers a stable infrastructure to
      ensure open, consistent, and effective participation and delivery of services.

PMID- 17554845
TI  - Efficiencies in health care regulation: observations near and far.

PMID- 17554846
TI  - Rising health care costs.

PMID- 17554847
TI  - The legal ramifications of best practices in health care.

PMID- 17554848
TI  - Provider response to cost containment: fraud & abuse issues.

PMID- 17554849
TI  - Provider response to cost containment: an insider perspective.

PMID- 17554850
TI  - Embracing complexity in drug discovery.

PMID- 17554851
TI  - Progress in standards for reporting omics data.
AB  - A number of research groups are generating standard mechanisms and prescriptions
      for reporting various kinds of biological and biomedical experiments. The motives
      for this generation include concern about the longevity of data sets (and the
      robustness of conclusions built upon them), the desire to integrate data from
      diverse scientific disciplines, and the facility to productively mine accrued
      data. The pharmaceutical industry continues to play a significant role in the
      genesis and development of such standards, in conjunction with technology vendors
      and academia. This review describes the context and nature of the new candidate
      standards and discusses their relevance to drug discovery and development.

PMID- 17554852
TI  - Lead optimization via high-throughput molecular docking.
AB  - Structure-based lead optimization approaches are increasingly playing a role in
      the drug-discovery process. Recent advances in 'high-throughput' molecular
      docking methods and examples of their successful use in lead optimization are
      reviewed. Measures of docking accuracy, scoring function comparisons, and
      consensus approaches are discussed. Differences in docking protocols typically
      used for lead optimization versus lead generation are highlighted; this section
      includes a discussion of the latest methods for the incorporation of protein
      flexibility. New approaches developed specifically for the design of
      combinatorial libraries as well as those designed or used for 'fragment' versus
      lead optimization are presented. Finally, potential future improvements to the
      technology are outlined.

PMID- 17554853
TI  - Molecular modeling of hydration in drug design.
AB  - The accurate prediction of the binding mode and affinity of a drug molecule to
      its putative receptor is crucial for successful drug design and optimization.
      Modeling the role of the aqueous solvent in ligand-protein interactions is one of
      the key components. Three main computational techniques have been developed to
      model hydration: free energy methods, ligand-protein docking and scoring, and the
      explicit inclusion of tightly bound water molecules in modeling. This review
      provides a summary of the most recent developments in these approaches used for
      the molecular modeling of hydration effects in the context of computational
      structure-based drug design methods.

PMID- 17554854
TI  - In silico identification of bioisosteric functional groups.
AB  - Bioisosteric replacement is a standard technique that is used in medicinal
      chemistry to design analogs of bioactive molecules with similar activity and with
      additional improved characteristics. However, successful bioisosteric design
      requires significant prior chemical knowledge, and the identification of a
      replacement group with an optimal balance of steric, hydrophobic, electronic and
      hydrogen-bonding properties that all influence ligand-receptor interactions
      usually requires a demanding procedure of trial and error. In this article,
      various methods that can help medicinal chemists to identify bioisosteric analogs
      are reviewed, beginning with classical techniques using experimental group
      properties. Methods to find bioisosteric pairs based on the analysis of large
      molecular databases are discussed. Various descriptors to characterize properties
      of functional groups are described, and methods to identify bioisosteric
      replacement by conducting property similarity search are presented. Examples of
      tools that help chemists to navigate within the group functional property space
      are also provided.

PMID- 17554855
TI  - Informatics and modeling challenges in fragment-based drug discovery.
AB  - This review summarizes recent developments in fragment-based drug-discovery
      methods with an emphasis on informatics and modeling requirements. Fragment-based
      methods have become established as a powerful approach in structure-based lead
      discovery. A number of successful projects have been announced recently, where
      fragments have had a central role in hit generation and lead optimization,
      leading to candidates being considered for clinical trials. Despite these
      successes, there are still many opportunities for new development, such as
      improving the structural diversity of fragment libraries, strategies for fragment
      evolution, and methods for predicting fragment binding modes.

PMID- 17554856
TI  - Virtual high-throughput screening of molecular databases.
AB  - Virtual high-throughput screening (vHTS) is an efficient and widely applicable
      method used to identify initial hit compounds for pharmaceutical research.
      Despite its widespread use, several aspects of protein structure-based vHTS can
      still be optimized, particularly its accuracy and speed in generating results.
      Recent developments that address these issues include machine learning and
      implicit solvation methods. Various machine learning methods are available to
      improve vHTS accuracy, for example, target-specific optimization of scoring
      functions, the integration of essential protein-ligand interactions, and the
      application of negative training data. Implicit solvation methods are exemplified
      by the molecular mechanics Poisson-Boltzmann solvent accessible surface area
      approach. Furthermore, grid computing and intelligent database screening
      approaches are used to improve the speed of vHTS.

PMID- 17554857
TI  - Ranking poses in structure-based lead discovery and optimization: current trends
      in scoring function development.
AB  - The ability to accurately predict the potency of ligand binding to its intended
      target prior to synthesis is of significant value in the drug-discovery paradigm.
      The protocols designed to this end follow a two-step process. First, ligands are
      docked into the active site of interest, and then the resulting interactions at
      the target are scored. Scoring functions form the key component in this process,
      providing a quantitative measure of fit quality. There is an abundance of new
      research in the field of scoring function design, from incorporation of novel
      descriptors (derived from first principles or empirical analysis) to function
      redesign based on improved data set handling. This article provides a brief
      overview on the state-of-the-art developments in the field, with particular
      reference to their performance in relation to expected outcomes.

PMID- 17554858
TI  - Molecular optimization using computational multi-objective methods.
AB  - Improving the profile of a molecule for the drug-discovery process requires the
      simultaneous optimization of numerous, often competing objectives. Traditionally,
      standard chemoinformatics methods ignored this problem and focused on the
      sequential optimization of each single biological or chemical property (ie, a
      single objective). This approach, known as single-objective optimization (SOOP),
      strives to discover a single optimal solution to the optimization problem.
      Implicitly, SOOP-based methods assume that the optimal solution for an objective
      will also be the optimum for any other objectives involved in the profiling of a
      molecule. However, when these other objectives are conflicting, as is often the
      case in drug discovery, the individual optima corresponding to the numerous
      objectives may vary substantially. Multi-objective optimization (MOOP) methods
      introduce a new approach for gaining optimality based on compromises and trade
      offs among the various objectives. MOOP aims to discover a set of satisfactory
      compromises that can in turn be used to discover the global optimal solution by
      optimizing numerous dependent properties simultaneously. MOOP methods have only
      recently been introduced to the field of chemoinformatics. This paper first
      presents a brief introduction to issues related to MOOP and then surveys the
      application of MOOP methods in the field of chemoinformatics.

PMID- 17554859
TI  - Physics-based methods for studying protein-ligand interactions.
AB  - The accurate prediction of relative or absolute ligand-binding affinities is
      challenging in both theoretical and practical aspects. However, with the aid of
      advanced computing power and sophisticated methodology development, physics-based
      free-energy calculations, which can be used to predict ligand-binding affinities,
      have become increasingly utilized in the field of structure-based drug design.
      This review summarizes recent progress made in developing and applying physics
      based methods to studying protein-ligand interactions, focusing on methods using
      molecular mechanics force fields. Applications of these methods include
      predicting ligand binding poses, enriching binders in virtual screening, and
      calculating relative and absolute binding free energies. Future directions for
      further improving current physics-based methods are also discussed.

PMID- 17554860
TI  - Prediction of immunogenicity for therapeutic proteins: state of the art.
AB  - Immunogenicity is a significant problem associated with protein therapeutics, but
      can be predicted in advance by in silico, in vitro, and in vivo tools, which can
      identifiy sequences within the therapeutic protein that, when processed by T
      cells, elicit an immune response. Recent developments in T-cell-dependent
      immunology relating to the immunogenicity of therapeutic products include the
      description of toll-like receptor ligands and the identification and
      classification of regulatory T-cells. A limitation in determining the relative
      immunogenicity of potential therapeutic proteins is the variance in the
      immunogenicity determined by in vitro or in vivo techniques in animal and human
      models. However, given the sophistication and high-throughput capacity of
      existing in silico tools and the availability of precise in vitro validation
      assays, accurate prediction of immunogenicity for therapeutic protein products,
      and more rapid translation of research discoveries into clinical success, may be
      within reach.

PMID- 17554861
TI  - Functional peptides by genome reverse engineering.
AB  - Computational biology and chemistry combined with high-throughput analytical
      technologies contribute to reduce operational costs and foster innovation in
      every phase of the discovery of bioactive molecules. In order for life science
      industries to continue to deliver at the required market rate, new concepts need
      to be implemented in research and development, and new sources of bioactive
      molecules should be investigated. The genomic revolution provides the necessary
      information to generate novel bioactive peptides by the computational dissection
      of genomes.

PMID- 17554862
TI  - Competitive Workflow: novel software architecture for automating drug design.
AB  - As industrialization of laboratory processes for drug discovery continues to
      gather momentum, the bottleneck has moved toward exploitation of this tide of
      information to enable better quality decisions. The development of information
      management systems to automate data and materials management can have a positive
      impact on productivity, as can increasingly sophisticated computer-aided
      molecular design approaches. However, as long as key decisions can only be taken
      by a small number of expert individuals working in a complex social environment,
      the impact of such innovations will be limited. This review describes Competitive
      Workflow, a distributed multi-agent system explicitly designed for the automation
      of decision making, currently the preserve of the expert. The approach builds on
      workflow architectures that capture best practice in information processing, but
      aims to extend these to model the tacit knowledge of the expert in the selection
      of alternative pathways through the workflow. The review also discusses recent
      developments in related workflow-management systems, particularly for information
      management and processing services front multiple sources, as well as distributed
      multi-agent approaches. A specific implementation of Competitive workflow--the
      Discovery Bus--and its application to meta-quantitative structure-activity
      relationship analysis is also described.

PMID- 17554863
TI  - [Noninvasive laser therapy for skin superficial venous malformations with long
      pulsed Nd:YAG laser].
AB  - OBJECTIVE: Conventional therapies for skin superficial venous malformations have
      demonstrated poor efficacy and many side effects. This prospective study assessed
      the effectiveness and safety of noninvasive long pulsed 1064 nm Nd: YAG laser
      therapy for superficial venous malformations. METHODS: Twenty-two patients, aged
      9 months to 67 years, skin types III, with skin superficial venous malformations
      were treated with the Nd:YAG laser at fluences of 140 - 150 J/cm2, with 6 mm spot
      size and double pulse model(pulse width 7 - 8ms, interpulse interval 20 ms).
      Contact cooling was used to protect epiderm. Patients were examined 1 month and 6
      months after the last treatment. Results Were graded as percent clearance in five
      groups: 0%, 1% - 25%, 26% - 50%, 51% - 75%, 76% - 100%. RESULTS: Twenty-two
      patients completed the study with maximal 5 treatment sessions. At 6 months after
      the final session, 76% - 100% clearance was observed in 96.3% of the treated
      sites, 100% improvement was observed in 37% of the treated sites. Pain during
      treatment was variably perceived by patients. Transient erythema were seen in 8
      (38.1%) patients, but could resolve in 1 day to 1 month. None of patients have
      purpura, permanent pigmentation change and scarring. CONCLUSIONS: Noninvasive
      long pulsed 1064 nm Nd: YAG laser is effective and safe enough for the treatment
      of skin superficial venous malformations and selectively remove superficial
      vessels. The side effects are minimal while ideal cosmetic results can be
      achieved.

PMID- 17554864
TI  - [Estrogen on stimulating the angiogenesis of children's hemangioma in vitro].
AB  - OBJECTIVE: To demonstrate that estrogen stimulates the angiogenesis of children'
      s hemangioma. METHODS: A piece of hemangioma biopsy was embedded in fibrin gel,
      and a model in vitro of angiogenesis of human hemangioma was then established.
      The angiogenesis of hemangioma in each group was interfered by the estrogen and
      tamoxifen. There were four groups divided into the followings: the group with
      estrogen, the group with tamoxifen, the group with estrogen + tamoxifen and the
      control. The dimension of newborn tubule area in the 3rd, 6th, 9th day after the
      culture was calculated to compare statistically differences among the groups.
      RESULTS: In the model of angiogenesis of hemangioma, microvessels grew out from
      the tissue sample in 2 to 3 days after the culture, and in 8 to 9 days a complex
      network of microvessels had been shown, the tending to inactivity. On the 3rd,6th
      and 9th day after the culture the dimension of newborn tubule area of the group
      of estrogen [(2.84 +/- 0.20) mm2 (12.93 +/- 0.85) mm2 (22.47 +/- 1.40) mm2] were
      larger than those of the control [(1.98 +/- 0.17) mm2, (7.51 +/- 0.48) mm2,
      (11.26 +/- 0.73) mm2]. Those of the group of estrogen + tamoxifen [(1.08 +/-
      0.11) mm2, (3.54 +/- 0.31) mm2, (5.72 +/- 0.40 mm2] and the group of tamoxifen
      [(1.13 +/- 0.14) mm2 (4.26 +/- 0.29) mm2, (6.08 +/- 0.42) mm2] were smaller than
      those of the groups of the estrogen and the control (P < 0.05). CONCLUSIONS: The
      estrogen may stimulate the angiogenesis of children's hemangioma, and the
      tamoxifen may reverse the process.

PMID- 17554865
TI  - [The expression and role of glucose transporter-1 in infantile hemangioma].
AB  - OBJECTIVE: To investigate the expression and role of glucose transporter-1
      (Glut1) in infantile hemangioma. METHODS: Fifty-two samples from infantile
      hemangioma, 25 in cavernous venous malformation, 9 in arteriovenous malformation,
      2 in capillary malformation and 5 in normal skin samples were involved in this
      study. The EnVision immunohistochemical stain was used to investigate the
      expression of Glut1 protein in these samples. RESULTS: In the early proliferating
      stage, a number of endothelial cells expressed Glut1. In the middle proliferating
      stage, most of vascular endothelial cells and scattered endothelial cells
      expressed Glut1. In the late proliferating stage, the expression of Glut1
      decreased quickly. In the involuting stage, all hemangioma samples didn't express
      Glut1. All of the samples from the cavernous venous malformations, arteriovenous
      malformations, capillary malformations and normal skin had no expression of
      Glut1. CONCLUSIONS: Glut1 may be one of the phenotypes of infantile hemangioma
      endothelial cells in their development, rather than the inherent character. The
      expression of Glut1 changes according to the metabolic need of infantile
      hemangioma cells.

PMID- 17554866
TI  - [Expression and significance of TRAIL protein and mRNA in hemangioma].
AB  - OBJECTIVE: To detect the expression of TRAIL protein and mRNA in hemangiomas and
      vascular malformations. METHODS: Sections of 33 proliferative hemangiomas,28
      involuting hemangiomas and 29 vascular malformations were immunostained for TRAIL
      protein, TRAIL mRNA was examined by in situ hybridization in these tissue.
      RESULTS: The TRAIL protein positive rates in proliferative hemangiomas,
      involuting hemangiomas, vascular malformations and normal skins were respectively
      45.45% (15/33), 78.57% (22/28), 0% and 0%. There were significant differences
      among the four pathologies (P < 0.01). The difference between proliferative
      hemangiomas and involuting hemangiomas was also significant (P < 0.01). The TRAIL
      mRNA positive rates were 66.67% (11/33), 89.29 (25/28), 0% and 0% respectively.
      There were also significant differences among the four pathologies (P < 0.01).
      The difference between proliferative hemangiomas and involuting hemangiomas was
      also significant (P < 0.01). CONCLUSIONS: TRAIL could induce endothelial
      apoptosis and cause regression of hemangiomas.

PMID- 17554867
TI  - [Ultrasonographic value for the complications of breast augmentation with
      injectable polyacrylamide hydrogel technique].
AB  - OBJECTIVE: To analyze ultrasonographic features for the complications of breast
      augmentation with polyamide hydrogel injection. METHODS: Clinical study was made
      for 101 patients who had received the polyamide hydrogel injection for
      augmentation mammoplasty by using the ultrasonographic examination. RESULTS: The
      195 treated breasts in 98 patients suffered from injectable layer disorder, 1
      breast for hematoma, 7 breasts in 5 patients for abscess (infection), 2 breasts
      in 2 patients for cancer and 3 breasts in 3 patients for fibroadenomas.
      CONCLUSIONS: Ultrasonography may be of great diagnostic value for the
      complications of breast augmentation with polyamide hydrogel injection.

PMID- 17554868
TI  - [Clinical analysis of complications of polyacrylamide hydrogel injection for
      augmentation mammoplasty in 118 cases].
AB  - OBJECTIVE: To analyze the clinical manifestations and explore suitable treatments
      for the complications induced by polyacrylamide hydrogel(PAHG) injection for
      augmentation mammoplasty. METHODS: The symptoms, physical signs and treatments of
      the 118 cases were analyzed and summarized. RESULTS: The complications included
      in nodule formation (54.2%), pain (33.9%), PAHG migration (7.6%) and acute
      mastitis in lactation (4.3%). Satisfactory clinical treatment results have been
      obtained after suitable treatments. CONCLUSIONS: The complications induced by
      PAHG injection for augmentation mammoplasty have increased following its widely
      use, the re-evaluation for this technique should be made, and more effective
      treatment should be considered.

PMID- 17554869
TI  - [Clinical breast reconstruction with various methods].
AB  - OBJECTIVE: To investigate and clarify the indications of breast reconstruction
      after mastectomy with various methods. METHODS: A clinical analysis was made,
      based on 44 patients with the 45 breasts who had received breast reconstruction
      after mastectomy in our hospital from 2003 to 2005. The methods of breast
      reconstruction included in tissue expander/implant (5 cases), implants covered by
      latissimus dorsi flap (13 cases), latissimus dorsi flap along (3 cases), DIEP
      flap (6 cases), TRAN flap (10 cases) and solid double-pedicle TRAM flap (8
      cases). RESULTS: All of the flaps survived well in total 40 patients (40 breasts)
      who were used a flap for breast reconstruction. Superficial skin necrosis
      occurred in 1 case with the method of tissue expander/implant; rupture of breast
      prosthesis and infection occurred in 1 case with the technique of implant with a
      latissimus dorsi flap; subcutaneous seroma occurred in 1 case with the method of
      DIEP flap; partial flap necrosis occurred in 2 cases with the method of TRAM
      flap. By the follow-ups of 3 - 12 months, the reconstructed breasts were well
      shaped and there were no complications such as abdominal hernia. CONCLUSIONS:
      These 6 methods for breast reconstruction achieved the satisfactory results for
      the requirement of breast reconstruction in Chinese women. With the development
      of plastic surgery technique, the indications of breast reconstruction were
      enlarged.

PMID- 17554870
TI  - [Surgical treatment of acquired ear defect].
AB  - OBJECTIVE: To explore surgical procedure for the treatment of acquired ear
      defect. METHODS: The ear reconstruction was carried out by using soft tissue skin
      expander and autogenous rib cartilage framework, Medpor framework, auricular
      prosthesis, and so on. RESULTS: The long-term follow-ups showed that the flap of
      reconstructed ear was ruddy, soft, with normal sensory function. The cartilage
      framework had no degeneration, absorption and deformation. The Medpor framework
      had no deformation. The contour of auricular prosthesis was vivid and the implant
      system was stable. In addition, the reconstructed ears were coincidence with the
      normal side on location, form and dimension. CONCLUSIONS: It may be a major
      method for traumatic ear reconstruction that the soft tissue skin expander with
      autogenous rib cartilage framework could be applied at present time. In some
      special circumstances, the soft tissue skin expander with Medpor framework and
      auricular prosthesis may be other helpful choices.

PMID- 17554871
TI  - [Application of both expanded cutaneous flap and temporoparietal fascia flap in
      ear reconstruction with Medpor framework].
AB  - OBJECTIVE: To investigate the feasibility and results of application of both
      expanded cutaneous flap and temporoparietal fascia flap in total ear
      reconstruction with Medpor framework. METHODS: The main procedure consists of two
      stages: Stage I-skin expansion; Stage II -auricle formation consists of
      orientation of Medpor implant and creation of coverage for the implant by both
      expanded skin flap and temporoparietal fascia flap. RESULTS: Twenty-two ears in
      22 unilateral microtia patients were constructed using Medpor implants covered
      with both expanded cutaneous flap and temporoparietal fascia flap over the last
      three years, they were accepted as pleasing by the patients. CONCLUSIONS:
      Application of both expanded cutaneous flap and temporoparietal fascia flap can
      assure no extrusion of Medpor implant in ear reconstruction. Either more, the two
      layers of transferred tissues will not affect the profile details of the
      reconstructed ear. And because the skin covering the framework and fascia is
      derived from mastoid region, the appearance and profile of the reconstructed
      auricle is true to nature and close to that of the opposite one.

PMID- 17554872
TI  - [Cutis verticis gyrata].
AB  - OBJECTIVE: To improve the recognition and treatment of Chinese cutis verticis
      gyrata. METHODS: Based on the review of the etiopathology, clinical features,
      diagnosis, classification and treatment of the disease in the literatures, six
      patients with the cutis verticis gyrata were treated with the skin graft or the
      expanded scalp flap. RESULTS: The operative effects were satisfactory during 6
      months to 5 years of the follow-ups. No recurrence was found in all cases. Two
      patients treated with skin graft had lead to baldness, four patients treated with
      the expanded scalp flap had been good appearance. CONCLUSIONS: The method of the
      expanded scalp flap is good and effective treatment for the cutis verticis
      gyrate.

PMID- 17554873
TI  - [The application of partial 3D reconstruction for the maxillofacial tumor
      resection with one-stage reconstruction].
AB  - OBJECTIVE: To introduce a novel digital surgery technique based on partial
      reconstruction of skull and its application in tumor resection and on-sport
      reconstruction surgery. METHODS: The partial 3d reconstruction according to CT
      scanning data was obtained to get 3d model of both tumor and normal skull, then
      to define the resection area on tumor data through people-computer interaction
      process, do reconstruction the simulation on the remained model, pre-fabricate
      the cutting template and custom the implant. The resection template to confirm
      the message in surgery simulation can be transferred to real surgery accurately.
      RESULTS: All the four cases by using this method showed great consistency of the
      real and simulated surgery and got a good appearance of reconstruction.
      CONCLUSIONS: The surgery simulation technique based on partial 3d reconstruction
      has great assistance to tumor resection and one-stage reconstruction surgery.

PMID- 17554874
TI  - [The clinical application of acellular urinary bladder submucosa to
      reconstructive the urethral duct of hypospadias patients].
AB  - OBJECTIVE: Attended to apply the acellular urinary bladder submucosa in the
      operation of the urethral duct reconstruction of penile hypospadias. METHODS: In
      2 cases, the urethral ducts were reconstructed by using the acellular urinary
      bladder submucosa as dorsal half of the urethra, while the preputial island flap
      as ventral side. In the other patient, the urethral plate was incised, similar to
      Snodgrass operation, the matrix was fixed to the corpora cavernosa beneath.
      RESULTS: Uroflowmetry and the urethroscopy were been performed in the one year
      follow up. A bell-shaped flow curve was obtained in the patient after
      urethroplasty using matrix graft combined with a local flap, and no fistula,
      stricture was found after a year or half a year follow-up. CONCLUSIONS: The
      freeze-dried acellular urinary bladder submucosa had three-dimensional network
      structure, and the acellular urinary bladder submucosa graft combined with
      preputial flap for hypospadias repair provided satisfactory functional results.

PMID- 17554875
TI  - [Treatment of the windblow hand deformity].
AB  - OBJECTIVE: To discuss the treatment of the windblow hand deformity. METHODS: We
      treat 18 patients with operations step by step. First phase: to improve the thumb
      function; Second phase: shift the flexor digitorum superficialis of the middle
      and little finger to improve the ulnar drift of the digits; Third phase : to
      solve the flection deformity of the palm and digits. RESULTS: We follow the
      patients for 6 - 72 months, only lost 3.11 of 15 patients have the thumb function
      recovered. 9 patients had their ulnar drift of the digits corrected, 2 patients
      partly corrected, 4 have relapse. 5 among the 15 patients were offered second
      operation, to have the ulnar arthrosis bursa contracted, using abduction splint,
      after rehabilitation 4 patients have the deformity corrected, 1 has partly
      corrected. CONCLUSIONS: Operation step by step is better for the complex windblow
      hand deformity, solve one major problem each time,and systemic rehabilitation
      therapy is needed for satisfied curative effect.

PMID- 17554876
TI  - [Liposuction in facial contour rejuvenation].
AB  - OBJECTIVE: To evaluate the effect of vacuum suction on facial shaping and
      cervicofacial rejuvenating. METHODS: Based on injection of swelling solution,
      vacuum suction was used in totally 327 cases, including local fat deposit in face
      or neck. RESULTS: Since 1993, we have carried out 327 case, satisfactory rate was
      up to 98%. CONCLUSIONS: This is an adaptable method for facial shaping and
      cervicofacial Rejuvenating, very good results can be achieved.

PMID- 17554877
TI  - [The anatomic study and clinical observation of the neurectomy of the nerve to
      the medial gastrocnemius muscle for calf reduction].
AB  - OBJECTIVE: To introduce a method to reduce the volume of medial gastrocnemius for
      calf reduction. METHODS: Tibial nerve and nerve branches were dissected and
      explored at popliteal region for morphometry in 20 cadaver-legs. The length,
      width and the origination position of the nerve to the medial gastrocnemius were
      measured and recorded. During surgery, the nerve to the medial gastrocnemius
      muscle were explored and cut off. The circumference and the shape of the leg were
      measured and recorded. RESULTS: The nerve innervating the medial gastrocnemius
      originates from the tibial nerve which lies in the fat tissue of popliteal space.
      In 8 cases (40%) there is only 1 branch to the medial gastrocnemius, and in 4
      cases (30%) there are 2 branches. In other 4 cases (30%) the medial sural
      cutaneous nerve originate from the nerve to the medial gastrocnemius. The nerve
      to the medial gastrocnemius muscle branch off at (- 6.6 +/- 13.7) mm; the width
      is (2.3 +/- 0.4) mm; the length is (42 +/- 12) mm. Neurectomy of the nerve to the
      medial gastrocnemius was performed in 16 cases. After operation, the
      circumference of the leg was reduced (3.5 +/- 1.1) cm averagely and the curve of
      the medial line of the calf was reduced. There is no obvious swelling in these
      cases and the patients were able to walk immediately after operation. The
      function of the leg was not obviously influenced. CONCLUSIONS: Neurectomy of the
      nerve to the medial gastrocnemius muscle was a safe and effective method for calf
      reduction.

PMID- 17554878
TI  - [Clinical study of preoperative analgesia for liposuction].
AB  - OBJECTIVE: To observe the effect of the preoperative analgesia with
      Oxycodone/Acetaminophen for liposuction. METHODS: In the double-blind, placebo
      controlled clinical trial, 40 patients undergoing the liposuction were randomly
      assigned into two groups which were received a single oral dose of
      Oxycodone/Acetaminophen or calcium gluconate respectively before the operation.
      The degrees of pain were evaluated by visual analogue scale (VAS) at the
      beginning and the end of the operation. Adverse effects and the overall
      satisfaction on analgesic therapy were assessed when operation finished. RESULTS:
      The VAS scores of the experimental group were significantly lower than the
      control group at the beginning and the end of operation (P < 0.05). There were no
      significant differences between the two groups in side effects (P > 0.05).
      CONCLUSIONS: Oxycodone/Acetaminophen could produce preemptive effect.
      Preoperative oral administration of Oxycodone/ Acetaminophen may provide patients
      with good analgesia in plastic and cosmetic operation.

PMID- 17554879
TI  - [Establishment of the database of female skull by the aesthetics].
AB  - OBJECTIVE: The three-dimensional (3D) craniofacial measurements were studied
      through the quantitative computed tomography (CT). The dynamic database of
      quantitative measurement of three-dimensional craniofacial bone was established
      as mandible in physiological position. METHODS: 170 aesthetics female were
      examined by spiral volumetric CT (GE SR-7000). 3D craniofacial bone images were
      reformatted and 3D measurements were performed in SUN Workstation respectively.
      33 points were defined in the 3-d craniofacial structure in screen, 14 distances
      and 11 angles were measured, and 12 ratios were calculated in each case. All data
      were transferred into the database based on the SPSS software. There is all
      information of one case (such as number, sex, age, distances, angers) in one row;
      each column is a measurement item. The mean, standard deviation, standard error,
      medium, coefficient of variation and 95% confidence interval of data can be
      calculated and the correlation, regression between several groups of measurement
      item can be proceeded by computer automatically in the dynamic database. RESULTS:
      3D craniofacial bone imagings were displayed in arbitrary views without
      disturbing superposition by using cutting, rotating and 3D measurement
      procedures. The large data volume provides more information of special
      relationship of skull base, zygomatic bone, maxilla, mandible and vertebra. The
      coefficient of variation of skull base is less than them of maxilla and mandible.
      The standard deviation of ratios is further smaller than the standard deviation
      of distances and angles. With stepwise regression, the equation is (Go - Go) Y =
      0.578X1 + 0.754X2 + 0.228X3 - 0.579X4 - 14.672; (Tz- Tz) : Y = 0.775X1 + 0.161X2
      + 0.348X3 + 0.201X4 + 27.730. CONCLUSIONS: The database offers reference of the
      studying of growth rule of craniofacial bone of aesthetics female. It will help
      improve diagnostic accuracy, staging of reconstruction, precision of corrective
      surgery, and follow-up patients.

PMID- 17554880
TI  - [Discoidin domain receptors (DDRs) expression in pathological scar fibroblast
      formation].
AB  - OBJECTIVE: To explore the role of discoidin domain receptors (DDRs) in the
      formation of the keloid. METHODS: The real-time quantitative PCR was used to
      compare the DDRs expression in the keloids and normal fibroblasts. RESULTS: The
      level of DDR1 expression was significantly higher in keloid than in normal
      fibroblast (20.98 vs 4.2, P <0.01; 7.9 vs 4.23, P <0.05). The level of DDR1
      expression in keloid was also higher significantly than that in hypertropic scar
      (20.98 vs 7.9, P < 0.01). However, the level of DDR2 expression was somewhat
      higher in keloid than in normal fibroblasts, the difference seemed not to be
      significantly in probability (358, 332 vs 278, P > 0.05). CONCLUSIONS: DDRs may
      exert effect on keloid cell behaviours.

PMID- 17554881
TI  - [Location of predisposing gene for one Han Chinese keloid pedigree].
AB  - OBJECTIVE: To locate the locus of predisposing gene for Han Chinese keloid
      pedigree. METHODS: One large Chinese keloid pedigree with affected family members
      in five generations was investigated and confirmed. Venous blood samples from 32
      members in this family were collected and extracted genomic DNA. Fas gene was
      assumed as one of the candidate genes resulting in keloids in this pedigree. Four
      markers, D10S1687, D10S1765, D10S1735 and D10S1562 next to the all known genes
      relating with apoptosis or tumorigenesis in the 10 Mbp region around Fas gene on
      chromosomes 10q23.31 were selected as microsatellite markers. Subsequently, these
      markers were amplified by PCR, and all PCR products were genotyped and the
      linkage analyses were performed. RESULTS: After linkage analyses,
      D10S1765LOD(ZMAX) was 1.74, D10S1735LOD(ZMAX) was 1.51. These findings supported
      the linkage. D10S1562LOD(ZMAX) was 0.59, which did not exclude the linkage. All
      LODs for D10S1562 were less than - 2, at 0 = 0.0 - 0.10, which excluded the
      linkage. CONCLUSIONS: This study provides the first genetic evidence that the
      predisposing gene for this Han Chinese keloid pedigree may be mapped to the
      region about 1 Mbp on chromosomes 10q23.31, between marker D10S1765 and D10S1735.

PMID- 17554882
TI  - [Experimental gene therapy of keloid in vivo using recombinant adenovirus coding
      for Fas gene with steroid hormone].
AB  - OBJECTIVE: To observe the gene therapeutic effects in vivo using prepared
      recombinant adenovirus coding for Fas gene with steroid hormone. METHODS:
      Transplant the keloid tissue into athymic nude mice and then observe the tissue's
      change after injecting Ad-fas (T) or Ad-Fas (B) followed by steroid hormone.
      RESULTS: (1) The keloid tissue shrinked slightly when adenovirus was singly
      injected. (2) The keloid tissue transplanted into athymic nude mice was seen
      significantly shrink after injection of Ad-Fas (T) or Ad-Fas (B) followed by
      steroid hormone. (3) The injection of Ad-Fas (T) or Ad-Fas (B) may be helpful to
      decrease the dose of steroid hormone which may significant depressed its side
      effect. CONCLUSIONS: (1) Due to the immune deficiency in nude mice, the
      conclusion can not be made that the single injection of adenovirus is invalid.
      (2) Gene therapy in vivo was also successfully completed using the newly built Ad
      Fas (T) and Ad-Fas (B). The results were satisfactory. The success in
      experimental study may pave a sound foundation for further gene therapy in
      keloid.

PMID- 17554883
TI  - [Mapping of the loss of heterozygosity for chromosome 1 pter-36.21 in keloid].
AB  - OBJECTIVE: The aim of this study was to investigate the loss of heterozygosity
      (LOH) on chromosome 1 pter-36.21 of keloid in order to locate the deletion areas
      probably harboring scar suppressor genes. METHODS: Using polymerase chain
      reaction ( PCR )-denaturing polyacrylamide gel electrophoresis, 25 samples of
      keloid tissues and peripheral blood were analyzed. RESULTS: 15 out of 25 samples
      of keloid tissues exhibited LOH in at least one microsatellite locus. There were
      deletions at more than one locus of one keloid tissue. No MSI was found. The
      frequency of LOH was remarkably higher in the keloid tissues (n = 25, 15, 60%)
      than in the normal control samples (n = 25, 1, 4%). The frequency of LOH in
      D1S243, D1S468, D1S507 and D1S199 was as following: (n= 25, 7, 28%), (n =25, 10,
      40%), (n = 25, 13, 52%) and (n= 25, 3, 12%). The frequency of LOH in D1S243,
      D1S468, D1S507 were statistically significant. CONCLUSION: The most common LOH
      occurred at D1S243-D1S468-D1S507 might imply the existence of potential tumor
      suppressor gene of a subset of keloid , while MSI on 1 pter-36.21 may not a
      crucial event.

PMID- 17554884
TI  - [An observation of the effects of the truncated septin2 on mouse epidermal cell
      and fibroblast].
AB  - OBJECTIVE: To construct eukaryotic expression vector of the truncated septin2 and
      investigate the influence on the cultured mouse epidermal cell and fibroblast in
      vitro exerted by the transgenic expression product. METHODS: The short splicing
      fragment was obtained by amplifying the reverse transcription product of the
      fetal mouse skin mRNA with PCR. Then its recombinant expression vector pcDNA3.1 (
      )/septin2s was constructed and used to transfect the mouse epidermal cell and
      fibroblast cultured in vitro. The expression of the foreign gene was detected
      with RT-PCR and the changes of cell proliferation were observed and analysed.
      RESULTS: RT-PCR results indicated that pcDNA3.1/septin2 was expressed in the
      cultured mouse epidermal cells and fibroblasts in vitro. We found that the
      epidermal cells accelerated their reproduction, but the fibroblasts had no
      obvious changes. CONCLUSION: We successfully constructed eukaryotic expressive
      vectors of pcDNA3.1/ septin2s and transfected it into mouse epidermal cells and
      fibroblasts in vitro. The results settle a basis for showing effect of septin2s
      on fetal mouse skin.

PMID- 17554885
TI  - [Identification and cell phenotype transdifferentiation of adipose-derived stem
      cells].
AB  - OBJECTIVE: To investigate the transdifferentiation of the ADSCs to epidermal
      cells. METHODS: ADSCs were isolated and cultured from rat adipose tissue by
      digestion of enzyme. ADSCs was identified by immunocytochemistry and flow
      cytometry. ADSCs were divided into four groups in order to induce: the condition
      medium (containing 30% superior of homogenizing rat skin in 10% FBS/DMEM) group,
      7 days; 10% FBS/DMEM with EGF (20 ng/ml) group, 7 days; the condition medium for
      4 days and then 10% FBS/DEME instead of the condition medium for 3 days group;
      10% FBS/DMEM for 7 days group (control group). Cytokeratin 19 and cytokeratin 10
      expressions in ADSCs were detected by flow cytometry. RESULTS: (1) The results of
      immunocytochemistry showed that ADSCs were positive for CD49d and negative for
      CD106, CD34, CD19, CD10. The results of flow cytometry showed ADSCs were positive
      for CD49d and CD44. (2) The CK19 expression of ADSCs was 45.32% in the condition
      medium group, 26.58% in the condition medium with EGF group, 23.37% in te
      condition medium for 4 days and then 10% FBS/DMEM instead of the condition medium
      for 3 days gropu and 18.53% in control group, P <0.01. The CK10 expression of
      ADSCs was 43.56% in the condition medium group, 25.54% in the condition medium
      with EGF group, 18.20% in the condition medium for 4 days and then 10% FBS/DMEM
      instead of the condition medium for 3 days group and 2.46% in control group, P <
      0.01. CONCLUSIONS: The superior of homogenizing rat skin can induce CK19 and CK10
      expressing in ADSCs, and thereby demonstrating ADSCs can differentiate to
      epidermal cell phenotype in vitro.

PMID- 17554886
TI  - [Experimental study of the eyelid reconstruction in situ with the acellular
      xenogeneic dermal matrix].
AB  - OBJECTIVE: To investigate the histocompatibility of acellular xenogeneic dermal
      matrix implanted in the rabbit eyelid reconstruction in situ and to compare the
      histological change of acellular xenogeneic dermal matrix and sclera replacing
      tarsus. METHODS: Thirty-six New Zealand rabbits were divided into two groups
      randomly. Establishment of the rabbits unilateral eyelid defect model, the eyelid
      reconstruction in situ were performed with either acellular xenogeneic dermal
      matrix or allogeneic sclera at random. The rabbits were clinically examined for
      inflammation and implant exposure and sacrificed 1, 2, 4, 6, 8 and 12 weeks after
      implantation. The eyelid with implant (Xeno-ADM or allogeneic sclera) were
      dislodged and the specimens were assessed histopathologically and
      ultrastructurally with light microscopies respectively for evaluation of change
      of juncture between implant and autoallergic tarsal plates including
      inflammation, vascularization and confluence. The 4, 8 and 12 weeks specimens
      were assessed with transmission electron microscope micro structural changes of
      the above organizations. RESULTS: Light microscopy and electron microscopy showed
      no statistical difference between two groups. But histological examination showed
      that eyelid implanted with acellular xenogeneic dermal matrix had less
      immunological and inflammatory reaction than sclera-implanted group. Acellular
      xenogeneic dermal matrix could induce neovascular and collagenous fibers into
      implanted tissue. CONCLUSION: Acellular xenogeneic dermal matrix is
      histocompatible to New Zealand rabbit, it can be used to support the eyelid as a
      substitution for tarsus.

PMID- 17554887
TI  - [Study on the optical and EPR spectra of CuAlS2: Ni+].

PMID- 17554888
TI  - [Comparison of the formation cross-sections of exciton in fluorescent and
      phosphorescent dyes].
AB  - In the present paper, polymer-based light-emitting diode employing N
      vinylcarbazole (PVK) doped with dilute phosphorescent dye factris-(2
      phenylpyridine) iridium [Ir(ppy)3] and fluorescent dye 4-(dicyanomethylene)-2-t
      butyl-6-(1,1,7,7-tetramethyljulolidyl-9-enyl)-4H-pyran (DCJTB) as active layer
      was fabricated in order to compare the formation cross-sections of triplet
      exciton and singlet exciton. According to the changes in the electroluminescence
      (EL) spectrum and the relative intensity of photoluminescence (PL) spectrum, we
      deduce that the exciton formation cross-section of Ir(ppy)3 is larger than that
      of DCJTB.

PMID- 17554889
TI  - [Research on theory and application of the interferogram of Voigt profile].
AB  - At normal pressure, Voigt profile (the convolution of Gaussian profile and
      Lorentzian profile) is the closest to actual profile, but it has no accurate
      expression, so in actual application many approximations are used to express
      Voigt profile. In the present paper, without any approximation, the authors
      calculate the interferogram of Voigt profile, showing that Voigt profile has no
      expression, but its interferogram can be calculated strictly. The transform has
      only one term, which is very similar to the expressions of Gaussian profile and
      Lorentzian profile, so any calculations of the widened profile can be finished,
      which doesn't have two terms as some papers predict, and difficulties will be
      brought. The calculation results are consistent with the experimental results. As
      an example in actual application, its application in atmospheric wind measurement
      is pointed out. This calculation has important significance in Fourier transform
      spectrometer of gas widened profile.

PMID- 17554890
TI  - [Preparation and luminescence properties of nanocrystals Gd2O3: Eu3+].
AB  - Nanocrystalline Gd2O3 doped with europium was synthesized by the low-temperature
      combustion method. By using the X-ray diffraction (XRD), high resolution
      transmission electron microscopy( HRTEM), and fluorescence spectrophotometer, the
      structural, morphological and luminescence properties of the nanocrystal were
      investigated. The results show that by varying the glycine-to-metal nitrate (G/M)
      molar ratio and the annealing temperature, nanocrystalline Gd2O3: Eu3+ with
      different structure and grain size could be achieved. The structure changed from
      cubic to monoclinic with the increment of G/M ratio after the samples had been
      calcined at 800 degrees C for 0.5 hour. When the G/M ratio was 0.83 and 1.0, the
      nanosized and pure cubic phase Gd2O3: Eu3+ was produced. The crystalline size
      became bigger with increasing the annealing temperature. The grain size was about
      10-30 nm. The main emission peak in cubic Gd2O3: Eu3+ nanocrystal was at 612
      nm(the (5)D0-->F2 transition). In addition, a red shift for charge transfer state
      occurred in the excitation spectrum.

PMID- 17554891
TI  - [The analysis of polarized display characteristic of LCLV].
AB  - The polarized TN effect of LCLV is discussed, and the twist of LC molecule with
      the AC voltage in LCLV is analyzed after its reorientation. While changing the
      applied voltage continuously at certain frequency, the twist angle of LC molecule
      in TB3639 LCLV and the electro-optical characteristic of the LCLV were measured.
      The results show that when the voltage is changed in series, the transmittance of
      the incidence linearly polarized light will alter continuously and nonlinearly,
      and the twist degree may control the nonlinear change. And the 1800 twist of the
      LC molecule will make the curve of electro-optical characteristic of the LCLV
      steeper, which allows multicenter matrix addressing LCLV to have more matrix
      lines and higher contrast.

PMID- 17554892
TI  - [Effects of spectral pretreatment on the prediction of crystallinity of wood
      cellulose using near infrared spectroscopy].
AB  - The crystallinity of wood has an important effect on the physical, mechanical and
      chemical properties of cellulose fibers. The aims of this study were to
      investigate the ability of near infrared spectroscopy (NIR) to predict the
      crystallinity of wood cellulose and the effect of spectral pretreatment on the
      prediction of crystallinity in wood cellulose using near infrared spectroscopy
      (NIR). Near infrared diffuse reflectance spectra were collected from wood powder
      with a fiber-optical probe and the crystallinity of wood was determined by X-ray
      diffractometer (XRD) in this experiment. The results showed that near infrared
      spectroscopy coupled with partial least square (PLS) regression could be
      correlated with the crystallinity of plantation wood, and the ability of NIR
      prediction based on original spectra was better than that based on the first
      derivative or second derivative treated spectra. There was a significant
      correlation between NIR spectra and XRD determined crystallinity with a
      correlationcoefficient of 0.950 and a low RMSEP. Near infrared spectroscopy
      coupled with multivariate data anlaysis has proven to be an accurate and fast
      method for rapid prediction of wood crystallinity.

PMID- 17554893
TI  - [Application of KNN method to cancer diagnosis using Fourier-transform infrared
      spectroscopy].
AB  - Early diagnosis and early medical treatments are the keys to save the patients'
      lives and improve their living quality. Fourier transform infrared (FTIR)
      spectroscopy can be used to distinguish malignant from normal tissues at the
      molecular level. In the present paper, programs were made with chemometrics
      method of pattern recognition to classify unknown tissue samples. Spectral data
      were pretreated by using smoothing, SNV and RHM method. Cross validation was used
      to test the discrimination effect of KNN method. A total of 63 gastric tissue
      samples were employed in this study, including 26 cases of normal tissue samples
      and 37 cases of cancerous tissue samples. The recognition results of the KNN
      method showed that the correctness of classification achieved 91.7%.

PMID- 17554894
TI  - [Study on the antioxidation property of engine oil by infrared spectroscopy].
AB  - The relationship between the engine oil' s infrared spectroscopic characteristics
      and its antioxidation property was studied, and the technical method to obtain
      the spectral information in accordance with the contribution of lubricating-oil
      composition to antioxidation property is presented. Quantitative self
      organization neural networks was developed by combining the advantages of BP
      neural networks and those of self-organization neural networks. Quantitative self
      organization neural networks possesses both the qualitative clustering function
      of self-organization neural networks and the quantitative analysis function of BP
      neural networks, and featuFes better robustness, so the quantitative analysis
      result of quantitative self-organization neural networks was better than that of
      BP neural networks. The result has provided a kind of new technology means for
      fast testing lubricating-oil performance.

PMID- 17554895
TI  - [Application of long open path FTIR system in ambient air monitoring].
AB  - A long open path fourier transform infrared spectroscopy system is described. The
      250-meter-optical-path configuration is combined with a Fourier transform
      spectrometer of 1 cm(-1) resolution. With an active blackbody source, the
      transmittance spectrum of the atmosphere could be measured by the system. And
      then, it was fitted with the nonlinear least square algorithm to calculate the
      average concentrations of the constituents in the path. Measuring result of some
      gases such as CH4, CO, N2O and CO2 in polluted air was presented in the
      experiment part and the RMS of the residuals was <1%. The result shows that the
      system is stable and rapid, and can be easily aligned. It is suitable for
      research work on some infrared active important atmospheric constituents.

PMID- 17554896
TI  - [Measurement of CO2 using an open-path FTIR and the factor of influence].
AB  - In the remote-sensing experiments of CO2 in Beijng, the authors found that the
      higher concentration of CO2 in autumn is caused by the CO2 emission by the
      traffic sector during the day time. During the day time, the concentratration of
      CO2 is comparatively lower because of the photochemistry and the transportation
      of troposphere. And the concentration of CO2 is about 410 microg x mL(-1). At
      night the fossil fuel power plants will be taken as a model for the source of
      CO2, so the concentration of CO2 is about 610 microg x mL(-1) or higher. The
      carbon increment from increased photosynthesis is greater than the increment in
      ecosystem carbon stocks. The higher the temperature, the lower the CO2
      concentration. And the lower the rate of wind, the higher the concentration of
      CO2 also. Besides, the concentration of CO2 is affected by some other weather
      factors.

PMID- 17554897
TI  - [A study of depositing amorphous SiOx films vis magnetron sputtering by FTIR
      method].
AB  - Amorphous SiOx films were deposited on Si substrates by magnetron sputtering
      technology. Three absorption bands of the SiOx films were detected by Fourier
      transform infrared spectroscopy. The authors' investigation shows that Si-Oy-Si(4
      y) (0 < y < or =4), Si6 rings, and non-bridging oxygen hole center defects were
      formed in the films with the sputtering power increasing. The appearance of the
      three absorption bands was due to the stretching and asymmetric stretching
      vibration of Si--O--Si bond and the vibration of O--Si--O bond corresponding to
      the above mentioned structures in the SiOx films.

PMID- 17554898
TI  - [Studies on acidity of chloroaluminate ionic liquids and its catalytic
      performance for alkylation of benzene with long-chain alkenes].
AB  - The acidity of chloroaluminate ionic liquids (ILs) was determined by using
      pyridine and acetonitrile as IR spectroscopic probes. Based on the
      characterization method of acidity of solid acid, IR vCCN absorption frequencies
      of pyridine in ionic liquids were assigned. By using the pyridine probe, it was
      found that when the anion molar composition x of ionic liquid varies within 0.4
      0.5, ionic liquids exhibit weak Lewis acidity. Strongly basic molecular pyridine
      can be used as a probe to measure the acidity of ionic liquids whether their
      acidity is strong or weak, while weakly basic molecular acetonitrile is only fit
      for strong acid. In addition, the Lewis acidity-activity correlation for the
      chloroaluminate ionic liquids catalyst in the alkylation reaction was studied.
      The weakly acidic ILs with x < or = 0.5 does not exhibit any catalytic activity
      in the alkylation reaction. When the anion molar composition x is more than 0.55,
      the activity of ionic liquids is greatly enhanced due to the increase in the
      strength of the strong Lewis acidic species Al2Cl7-. But with the increase in
      alkenes conversion, the selectivity of 2-alkylbenzene is slightly reduced.

PMID- 17554899
TI  - [Identification of reconstructed milk in raw milk using near infrared
      spectroscopy].
AB  - Feasibility of reconstituted-milk identification in raw milk was investigated
      using near infrared spectroscopy. And the applicability of MSC for reconstituted
      milk identification was discussed. The discrimination analysis calibration was
      developed by SIMCA method, and the result indicated that the accuracy of
      detection is 100%, when the content of reconstructed Milk is above 20%, while for
      the 10% reconstituted milk, the accuracy of detection is 96.7%; On the other
      hand, the quantity models of reconstituted milk were calibrated by partial least
      squares regression (r = 0.971, RMSECV = 7.76%, RPD = 5.13), and there were no
      significant differences between actual value and reconstituted milk prediction
      value by t test (p = 0.01). All of these suggested that NIRS has good potential
      to detect adulteration of raw milk with reconstituted milk.

PMID- 17554900
TI  - [Optical spectral verification of a harmful impurity to palladium catalyst].
AB  - The condensation of glyoxal with benzylamine leaded to hexabenzyl
      hexaazaisowurtzitane (HBIW) with formic acid catalyst, and at the same time some
      side products were produced. Some impurities in HBIW would be harmful to the
      palladium catalyst used in the hydrogenolysis of HBIW, subsequently resulting in
      the low yield or failure of the catalytic reaction. The impurities in
      hexabenzylhexaazaisowurtzitane were distilled by means of recrystal technic,
      which were isolated by preparative chromatograph. The structure of the main
      impurity was studied with FTIR, 1H-NMR, ESI-MS, and element analysis. The result
      shows that the structure is comfirmed as N,N'-dibenzyl-oxalamide. which was
      synthesized in the way reported in the literature, and was charactered by FTIR,
      1H-NMR and EI-MS. And the optical spectra data of the sample synthesized and the
      substance isolated from the impuries were the same, testifying that the substance
      isolated was N, N'-dibenzyl-oxalamide ulteriorly. N, N'-dibenzyl-oxalamide was
      added in the hydrogenolysis system of HBIW catalyzed by Pd catalyst. The result
      shows that N, N'-dibenzyl-oxalamide can reduce the activity of Pd catalyst, and
      when the quantity of N,N'-dibenzyl oxalmine added achievs 0.9% of the weight of
      HBIW, the reaction of catalytic hydrogenolysis fails.

PMID- 17554901
TI  - [Measurement of moisture and oil content in gross cottonseed based on near
      infrared reflectance technique by open detecting mode].
AB  - In the present paper, the moisture and oil content in gross cottonseed analyzed
      by near infrared reflectance spectroscopy (NIRS) technique was studied. Including
      the basic theory of NIRS and advantage of open detecting mode. The calibrations
      of the moisture and oil content in gross cottonseed were performed. The precision
      and accuracy of the moisture and oil content were clarified by random sampling.
      The correlation coefficient is high: 0.965 for moisture and 0.953 for oil. The
      calibration errors (SECV) for the moisture and oil content in gross cottonseed
      are 0.226 and 0.391 repectively. The result of NIRS prediction has been proved
      that the NIRS method can replace the normal analysis method completely. Further
      studies on the calibration of oil content in nucleus and rate of nucleus in gross
      cottonseed were carrced out with part of samples. It has been proved that NIRS
      method can be applied to detect the oil content in nucleus and rate of nucleus in
      gross cottonseed.

PMID- 17554902
TI  - [Research on the making process of connective seal by using FTIR imaginge
      system].
AB  - Seal's determination is the important part of forensic science. In order to
      better beat criminality, the authors brought forward a new method to study the
      making process of connective seal fast and nondestuctively by means of FTIR
      imagine System. Combining the surface scan and reflectance mode, the different
      part of connective seal was scaned firstly, then according to the characteristic
      absorption proportion of stamp-pad ink it was determined whether the connective
      seal was one-off made or not. The results showed that if the connective seal was
      one-off made, the characteristic absorption proportion was equal. This method is
      rapid, accurate, impersonal and nondestructive.

PMID- 17554903
TI  - [Quantitative prediction of active constituents in rhubarb by near infrared
      spectroscopy and radial basis function neural networks].
AB  - Near infrared spectroscopy (NIRS) and artificial neural networks were used for
      the quantitative prediction of four active constituents in rhubarb:
      anthraquinones, anthraquinone glucosides, stilbene glucosides, Tannins and
      related compounds. The near infrared spectra of the samples were acquired in 1100
      2500 nm from powdered rhubarb samples. Four calibration models using radial basis
      function neural networks (RBFNN) were set up to correlate the spectra with the
      values determined by HPLC. RMSECVs of the models for the constituents studied
      were 2.572, 0.442, 2.794 and 9.438, respectively. RMSEPs for the were 4.598,
      8.657, 0.4586, and 5.106, respectively. The method is fast, and satisfactory
      results were obtained. The proposed method can be used for determining the active
      constituents in Chinese herbal medicine.

PMID- 17554904
TI  - [Common and variant peak ratios in IR fingerprint of ilex kudingcha with duel
      index sequence analysis].
AB  - In the present article, two new indexes, common peak ratio and variant peak
      ratio, were applied and their values were calculated by means of sequential
      analysis, in which each Ilex Kudingcha sample s IR fingerprint spectra were set
      up and the common peak ratio sequences were arranged in order of size in
      comparision with other samples. As a result, the method could be used to
      distinguish Ilex Kudingcha of different areas and classes. The duel-index
      sequential analysis enables us to distinct two or more herb's IR fingerprints. It
      is a new method to analyze IR fingerprint spectra, and can used in line with the
      characteristics of traditional Chinese medicine.

PMID- 17554905
TI  - [Analysis of saponin in Chinese ginsengs by NIR spectroscopy].
AB  - In the present paper the saponin in Chinese ginseng was analysed quantitatively
      by using near infrared spectroscopy. The spectral characteristics of the primary
      ingredients in Chinese ginseng were obtained by applying second derivative, MSC
      (Multiple Scatter Correction), and correlation chart to the original absorbance
      spectra of ginseng. Meantime, in combination with the PLS algorithm the
      calibration process was performed for the quantitative analysis of saponin in
      Chinese ginseng. The result obtained shows a fine precision of the method, with
      RMSEC of 0.154% and correlation coefficient of 0.9828.

PMID- 17554906
TI  - [Estimation of soluble solids content of apple fresh juice by FTNIR
      spectroscopy].
AB  - The feasibility of Fourier transform near infrared (FTNIR) spectroscopic
      technology for rapid quantifying the soluble solids content (SSC) of apple fresh
      juice was investigated by means of spectral transmittance technique. A total of
      60 juice samples were used to develop the calibration models. The relationship
      between laboratory SSC and FTNIR spectra of apple fresh juices was analyzed via
      principal component regression (PCR) and partial least squares (PLS) regression
      method using TQ 6.2.1 quantitative software. Models based on different spectral
      ranges were compared. Performance of different models was assessed in terms of
      root mean square errors of prediction (RMSEP) and correlation coefficients (r2)
      of validation set of samples. The best prediction models had a RMSEP of 0.603
      degree Brix and correlation coefficient (r2) of 0.997 for SSC. The results show
      that FTNIR transmittance technique is a feasible, accurate and fast method for
      non-invasive estimation of fruit fresh juice soluble solids content.

PMID- 17554907
TI  - [Measurement of chlorophyll content in pepper leaves by near infrared analysis].
AB  - The objective of this research was to study the potential of NIR diffuse
      reflectance spectroscopy for nondestructive measurement of chlorophyll content in
      pepper leaves. Statistical models were developed using partial least squares
      (PLS) and principal component regression (PCR) analysis technique, and four
      different mathematical treatments were used in spectra processing: smoothing,
      baseline correction, different wavelength range, and first and second derivative.
      The results showed that smoothing and baseline correction of NIR original spectra
      had little influence on spectral data analyzing, second derivative spectra showed
      better results than first derivative spectra and original spectra, while PLS
      analysis could get better modeling results than PCR analysis. The best
      calibration model was obtained after removing four outlier samples, and
      processing spectra with second derivate in the full wavelength range, with the
      highest correlation coefficient (r = 0.97537), a relative lower RMSEC value
      (2.33), and a small difference between RMSEC (2.33) and RMSEP (5.49). It can be
      concluded that NIR technique is a feasible, nondestructive way to predict the
      chlorophyll content in pepper leaves.

PMID- 17554908
TI  - [Fast discrimination of varieties of bayberry juice based on spectroscopy
      technology].
AB  - Visible and near-infrared reflectance spectroscopy (NIRS) was applied in the
      discrimination of bayberry juice varieties. Characteristics of the pattern were
      analyzed by partial least square. Through full cross validation, nine principal
      components presenting important information of spectra were confirmed as the best
      number of principal components. Then, these nine principal components were taken
      as the input of BP neural network. Through the training and prediction, three
      different varieties of bayberry juice were classified according to the outputs of
      BP neural network. Besides, the work on building mathematic model and optimizing
      the algorithm was completed. In the process of BP neural network modeling, 60
      samples were gained from the local market and each species has 20 samples. Fifty
      one samples were used as the training set and the reminder samples (total 9
      samples) formed the prediction set. With a proper network training parameter, a
      100% accuracy was obtained by BP neural network. Thus, it is concluded that PLS
      analysis combined with BP neural network is an available alternative for pattern
      recognition based on the spectroscopy technology.

PMID- 17554909
TI  - [Application of reflection infrared sensor to intelligent water-saving system].
AB  - Utilizing reflection type infrared sensor and small electronic devices
      (monostable multivibrator), the authors have developed the intelligent water
      saving control system. This system can discern whether someone enters the
      lavatory, produce the signal of washing according to the cirumstances, drives the
      electromagnetic valve to open, and pour water into the floater type cistern.
      After filling two cisterns of water enough for cleaning, it'll cut off the power
      in the electromagnetic valve automatically. This system has achieved the sanitary
      and economical purpose, using this system can economize water by about 70%. This
      system features few components, low costs, rational structure, reliable work,
      easy installation, and convenient maintenance, so it has a wide application
      prospect.

PMID- 17554910
TI  - [Interaction of ctDNA and EGCG-Cu(II) complex].
AB  - The fluorescence spectra, absorption spectra and resonance light scattering (RLS)
      spectra of EGCG-Cu((II) complex with nucleic acid were studied. Compared with the
      spectrum of EGCG-Cu(II), the spectrum of EGCG-Cu(II)-DNA system showed the
      following features: (1) in the fluorescence spectra, the peak did not shift, but
      the fluorescence intensity was enhanced and was proportional to the concentration
      of DNA. Under suitable conditions, EGCG-Cu(II) promised to be a probe for
      detecting DNA; (2) Absorption spectra of EGCG-Cu(II)-DNA system showed
      hyperchromicity; and (3) RLS of EGCG-Cu(II)-DNA system was enhanced also. A
      mechanism was suggested that the combination of nucleic acid and EGCG-Cu(II)
      complex was caused by intercalation and electrostatic force. An intercalation
      interaction between EGCG-Cu(II) and DNA enhanced the fluorescence intensity.
      Hyperchromicity of absorption spectra and RLS occurred because of electrostatic
      force. The effects of acid and ionic strength on fluorescence intensity were also
      discussed.

PMID- 17554911
TI  - [Estimations of chlorophyll and water contents in live leaf of winter wheat with
      reflectance spectroscopy].
AB  - For estimating the yield of wheat, and for crop growth monitoring by using
      hyperspectral remote sensing, it is very important to quantitatively determine
      the chlorophyll and water contents in live leaf of winter wheat. In the range of
      350-1650 nm, the reflectance spectrum of winter wheat's leaf in different growth
      periods were scanned by ASD FieldSpec Pro FR portable spectrometer and LI-COR
      1800 integrating spheres. Partial least squares method was used to develop the
      quantitative analysis models for chlorophyll and water contents with reflectance
      spectroscopy. The model of chlorophyll content with reflectance spectroscopy was
      built in the range of 400-750 nm, and the results show that the correlation
      coefficient between the estimated values and the real values is 0.898, and
      relative standard deviation is 13.6%. The model of water content with reflectance
      spectroscopy was built in the range of 1400-1600 nm, and the results indicate
      that the correlation coefficient between the estimated values and the real values
      is 0.999, and relative standard deviation is 0.3%. These results are satisfying
      in agricultural production.

PMID- 17554912
TI  - [Interaction between carbaryl and calf thymus DNA enhanced via Cu2+].
AB  - The interaction between carbaryl and calf thymus DNA with Cu2+ was studied using
      fluorescence spectroscopy (FS) and UV spectrum. The quenching process was proved
      to be single static quenching and the quenching constant decreases with
      temperature increasing. The experimental results showed that the carbaryl can be
      intercalated into the twin-screw structure of calf thymus DNA, forming ctDNA
      carbaryl adducts. The UV spectrum showed that ctDNA can also result in the
      increasing color and red shift. In the presence of Cu2+, it was discovered that
      the apparent association constant (Kalpha) increases and the binding sites number
      (n) of carbaryl molecules on ctDNA obviously increases. The interaction of the
      carbaryl and ctDNA was driven mainly by electrostatic force which was enhanced by
      Cu2+, thus the contribution of deltaH to deltaG increased in the presence of Cu2+
      So the interaction between carbaryl and calf thymus DNA was enhanced via Cu+.

PMID- 17554913
TI  - [Study on exploring for oil and gas using reflectance spectra of surface soils].
AB  - Reflectance spectra in the visible and near-infrared wavelength region provide a
      rapid and inexpensive means for determining the mineralogy of samples and
      obtaining information on chemical composition. Hydrocarbon microseepage theory
      sets up a cause-and-effect relation between oil and gas reservoirs and some
      special surface alterations. Therefore the authors can explore for oil and gas by
      determining the reflectance spectra of surface alterations. This determination
      can be fulfilled by means of field work and hyperspectral remote sensing. In the
      present paper, firstly a macroscopical feature of reflectance spectra of typical
      observation points in gas fields is presented. Then a method is proposed in order
      to provide surface distribution information (e.g., classification) of alterations
      based on the reflectance spectra determined from the field, and obtain anomaly
      zones of the special alterations. This method has been applied to the analysis of
      the reflectance spectra determined in the field of Qinghai X X area, and the
      classification results tally with the existent gas fields in this area. A
      robustness analysis of the method shows that good results can be obtained when
      different combinations of parameters, such as samples, study band regions and
      thresholds, have been chosen in the process of classification. The valid
      classification samples and algorithms can be provided for the oil and gas
      exploration in progress in this area using NASA experimental hyperion
      hyperspectral satellite.

PMID- 17554914
TI  - [Influence of inert nuclei (La3+, Y3+ and Gd3+) on fluorescence of europium
      complex with phenylglyoxylic acid and phenathroline].
AB  - Three series of dinuclear complexes (Eux RE(1-x) L3 phen) of phenylglyoxylic acid
      and phenathroline with different molar ratios of Eu3+ to inert nuclei (RE = La3+,
      Y3+ and Gd3+) were synthesized. Their excitation and emission spectra were
      studied. The excitation spectra showed that the optimum excitation wavelengths of
      the complexes are all in the range of 350-360 nm, which belong to the excitation
      peaks of ligands, and the weak excitation peak of Eu3+ is at about 398 nm; The
      emission spectra showed that there are five emission bands at about 583, 595,
      617, 654 and 703 nm respectively for all the complexes, due to (5)D0 - (7)F0,
      (5)D0 - (7)F1, (5)D0 - (7)F2, (5)D0 - (7)F3 and (5)D0 - (7)F4 transitions of Eu3+
      respectively. The authors also found that the emission peak positions of Eu3+
      shift the most in the complexes Eu(x) La(1-x) L3 phen, the position of (5)D0 -
      (7)F2 transition shifts 5.2 nm when the molar ratio of Eu3+:La3+ is 0.3: 0.7, but
      the addition of Y3+ and Gd3+ makes the emission peak positions of Eu3+ change
      less than that of La3+. Meanwhile the luminescence intensity of Eu3+ can be most
      enhanced by La3+ in all the complexes. The conclusion we found in the present
      paper could help search the luminescence materials with low cost and good
      luminescence properties.

PMID- 17554915
TI  - [Study on the fluorescence characteristics of the interaction between DNA and two
      halogenated fluoresceins].
AB  - The fluorescence characteristics of the interaction between DNA and two halogen
      fluoresceins, tetrabromofluorescein (TBF) and tetrachlorotetrabromofluorescein
      (TTF), were studied. The result showed that for TBF, lamda ex/ lamda em were 518
      nm/540 nm, and for TTF, they were 540 nm/560 nm. The intensity of fluorescence of
      TBF and TTF changed in the presence of DNA. The fluorescence quenching studies
      indicated that TBF binds to DNA in the groove and the polarization experiments
      showed that TBF is intercalated into the DNA base pairs. So the comprehensive
      interaction mode of TBF with DNA may be that TTF is intercalated into DNA base
      pairs and binds to DNA in the groove. Both the fluorescence quenching studies and
      the polarization experiments indicated that TTF is intercalated into the DNA base
      pairs. It was also found that ionic strength could affect the interaction of
      TBF/TTF and DNA. The binding constants K are 1 x 10(6) L x mol(-1) and 2 x 10(6)
      L x mol(-1), and the binding site numbers n are 0.62 and 0.16 for TBF and TTF,
      respectively.

PMID- 17554916
TI  - [Study on the fluorescence characteristic and mechanism of ether-water solution].
AB  - The fluorescence spectra of low concentration diethyl ether-water solution
      excited by different UV light, and the variation rule of the fluorescence
      characteristic along with the incidence light wavelength and the solution
      concentration were studied. Also the emission mechanism together with the
      spectral characteristic were analyzed. The result shows that the ether solution
      exhibits an obvious fluorescence peak nearby 306 nm, for which the best
      excitation wavelength is 245 nm, moreover, there is an inferior peak at 292 nm.
      The shape of the fluorescence spectrum is invariable ultimately along with the
      change in excitation light wavelength, and the peak value assumes the Gaussian
      distribution with the stimulation light wavelength. Meanwhile the emission
      intensity of the inferior peak and that of the prominent peak are in competition
      with each other. With increasing the concentration, the fluorescence intensity at
      306 nm strengthens linearly, and after increasing the concentration to 7%,
      concentration-quenching occurs, so the intensity linearly weakens. The findings
      can provide the reference for detecting concentration and purity of the virulent
      and anesthetic matter-diethyl ether and so on.

PMID- 17554917
TI  - [Synthesis, characterization and fluorescence of Eu3+, Tb3+ complexes with 2
      thiophencarboxylic acid and 2,2'-bipyridine].
AB  - Two binary complexes of Eu3+ and Tb3+ with 2-thiophene carboxylic acid and two
      ternary complexes of Eu3+ and Tb3+ with 2-thiophene carboxylic acid(L)-2, 2'
      bipyridine were synthesized. By elemental analysis, rare earth coordination
      titration, and molar conductivities studies, the compositions of the complexes
      were suggested as REL3 x 2H2O and REL3L' x C2H5OH(RE=Eu, Tb, L = 2-thiophene
      carboxylic acid, L' = 2, 2'-bipyridine) respectively. The ligands and
      coordination compounds were studied by means of IR spectra, 1H NMR and
      fluorescence excitation and emission spectra. IR spectra and 1H NMR studies
      indicate that 2-thiophene carboxylic acid was bonded with RE(III) through oxygen
      atoms in the carboxyl group, and 2, 2'-bipyridine ligand was bonded to RE(III)
      through nitrogen atoms. The fluoresence spectra showed that the fluorescence
      emission intensity of ternary complexes was stronger than that of the binary
      complexes.

PMID- 17554918
TI  - [Spectral study of monoisothiocyanato-substituted 3:1 asymmetrical phthalocyanine
      zinc(II)].
AB  - Electronic absorption spectra of three monoisothiocyanato-substituted
      asymmetrical phthalocyanine zinc(II), 2-isothiocyanato-9,10,16,17,23,24
      alkyloxyphthalocyanine zinc(II) [(RO)6 (NCS)PcZn(II)] (R = n-C4H9, n-C5H11, n
      C10H21), were measured in five organic solvents. The effect and order of the
      substitute groups and solvents were studied by electronic absorption spectra. The
      changes of lamda(max) data are very small between monoamino- and
      monoisothiocyanato-substituted asymmetrical phthalocyanines. The order of
      lamda(max), data is listed here, CHCl3>CH2Cl2>toluene in non-coordination
      solvents; DMF>THF in O-coordination solvents. The fluorescence spectra of these
      complexes were measured in organic solvents at the same time. The effect and
      order of the substitute groups, solvents and concentrations were studied on the
      maximum wavelength of emission and fluorescence intensity. The lamda(em,max) data
      of fluorescence emission are among 690-700 nm. The order of lamda(em,max) data is
      listed here, DMF>THF in O-coordination solvents and almost the same in non
      coordination solvents. The fluorescence intensity is very strong in DMF and THF.
      The order of fluorescence intensity is listed here, DMF>THF in O-coordination
      solvents; toluene> CH2Clz > CHCl3 in non-coordination solvents. They have special
      fluorescent effect and should be expected to become a photosensitizer of
      photodynamic therapy in future.

PMID- 17554919
TI  - [Study of scavenging activity of sorghum pigment to hydroxyl free radicals by
      fluorimetry].
AB  - A natural product, sorghum pigment, consists of a number of important flavonoid
      derivatives, occurrs on the seed capsules or in the stems of many sorghums, and
      is widely applied in different fields of food, cosmetic and dyeing industries, It
      is important for scavenging hydroxyl free radicals and protection of human
      healthiness. Scavenging capacities of hydroxyl free radicals with sodium nitrite,
      quercetin and sorghum pigment were comparatively researched by fluorimetry, and
      the model of hydroxyl free radicals produced is based on the reaction of Cu2+ 
      catalyzed oxidation of ascorbic acid in the presence of hydrogen peroxide. The
      hydroxyl radicals react with benzoic acid, forming a fluorescent product, and the
      fluorescence intensity was determined by the concentration of hydroxybenzoic
      acid. The experimental results show that the sodium nitrite, quercetin and
      sorghum pigment have a quantity-effect relationship for scavenging hydroxyl free
      radicals, and sodium nitrite and quercetin in comparison with sorghum pigment
      have high antioxidant capacity. Finally, the quenching mechanisms were explored
      with sodium nitrite, sorghum pigment, and quercetin respectively. The sorghum
      pigment and sodium nitrite feature a dynamic quenching processes, while quercetin
      shows a static quenching processes. A reference method was provided for
      reasonable exploitation and utilization of sorghum pigment.

PMID- 17554920
TI  - [Selected enhancement of different order stokes lines of SRS by using
      fluorescence of mixed dye solution].
AB  - A new method to enhance the intensity of the different orders of Stokes lines of
      SRS by using mixed dye fluorescence is reported. The Stokes lines from the second
      order to the fifth-order of CCl4 were enhanced by the fluorescence of mixed R6G
      and RB solutions in different proportions of 20:2, 20:13 and 20:40 (R6g:Rb),
      respectively. It is considered that the Stokes lines from the second-order to the
      fifth-order are near the fluorescence peaks of the three mixed solutions, and far
      from the absorption peaks of R6g and Rb, so the enhancement effect dominates the
      absorption effect; as a result, these stokes lines are enhanced. On the contrary,
      the first-order stokes line is near the absorption peak of RB and far from the
      fluorescence peaks of the mixed solutions, which leads to the weakening of this
      stokes line. It is also reported that the first-order, the second-order and the
      third-order Stokes lines of benzene were enhanced by the fluorescence of mixed
      solutions of R6g and DCM with of different proportions. The potential application
      of this method is forecasted.

PMID- 17554921
TI  - [Research on characterization analysis of synchronous fluorescence spectra of
      living phytoplankton].
AB  - The synchronous fluorescence spectra of five phytoplankton species growing under
      three temperatures (25, 20 and 15 degrees C)and three illuminations (7000, 4100
      and 1100 Lx)were measured and processed by multinomial smoothness and autoscaling
      to obtain the characteristic spectra. Principal component analysis was used to
      obtain standard spectra. The analysis shows that at different temperatures, the
      characteristic spectra of Skeletonema costatuma, Isochrysis galbana, and
      Platymonas helgolanidica show high similarities, while the spectra similarities
      of Alexandrium tamarense and Gymnodinium stein are not as good as the above three
      species. The standard spectrum of Skeletonema costatuma, which belongs to
      Bacillariophyta, is quite different from those of Alexandrium tamarense and
      Gymnodinium stein, which belong to Dinophyta.

PMID- 17554922
TI  - [Spectra derivative kalman filter method for simultaneous spectrophotometric
      determination of phenol, 2-chlorophenol and 2,4-dichlorophenol].
AB  - A novel and stable spectra derivative Kalman filter UV spectrophotometric method
      was proposed, and applied to the simultaneous determination of ternary mixture of
      phenol, 2-chlorophenol and 2,4 dichlorophenol successfully. The reasons for using
      spectra derivative is that it contains more information including absorbance and
      its change with wavelength; the obviously different signals can be caught more
      conveniently at the position of absorbent overlap. The noise from experiment and
      the errors from transfer model can be solved by Kalman filter. Calibration set
      with 30 standard solutions (range of 1-10 mg x L(-1)) and 61 wavelengths (260-290
      m, 0.5 nm slit width) was used for each sample. The exact value of absorbance
      derivative was obtained from regressed simulation for the extended 8th order
      polynomial, and the standard work matrix of derivative spectra Kalman filter was
      performed from partial least-squares method. The linear discrete Kalman filter
      was applied to the test. The recovery experiment showed that the derivative
      spectra Kalman filter simultaneous determination of mixture for phenol, 2
      chlorophenol and 2,4 dichlorophenol is not only exact, but also stable.

PMID- 17554923
TI  - [Study on the effect of electric field on the secondary structure of HRP by
      circular dichroism].
AB  - After the HRP was treated with different strength of electric field, the effect
      of electric field on the secondary structure of HRP was studied by circular
      dichroism. The results show that different electric field strength ranging from
      1.0 to 6.0 kV x cm(-1) has a different effect on the relative contents of alpha
      helix, beta-sheet, beta-turn and random coil of the HRP. As compared with the
      contrast, the relative contents of alpha-helix, beta-turn and random coil
      decreased by 0.3%-11.4%, 1.7%-15.3% and 0.9%-20.4% respectively, while beta-sheet
      content increased by 0.9%-82.7%. The electric treatment tends to transform the
      alpha-helix, beta-turn and random coil into beta-sheet for the HRP. The result of
      this study has important meaning to explain the biological effect of electric
      treatment seeds.

PMID- 17554924
TI  - [Visible transmittance techniques for rapid analysis of sugar content of fresh
      navel orange juices].
AB  - The feasibility of visible spectroscopic technology for rapid quantifying sugar
      content (SC) of navel orange fresh juices was investigated by means of spectral
      transmittance technique. A total of 55 juice samples were used to develop the
      calibration and prediction models. Calibration models based on different spectral
      ranges and different spectral pretreatment were compared in the precent research.
      Performance of different models was investigated in terms of root mean square
      errors of prediction (RMSEP) and correlation coefficient (r) of validation set of
      samples. The correlation coefficient of calibration model for SC was 0.965, the
      correlation coefficient of prediction model for SC was 0.857, and the
      corresponding RMSEP was 0.562. The results show that visible transmittance
      technique is a feasible method for non-invasive estimation of fruit juice SC.

PMID- 17554925
TI  - [Study and spectrophotometric determination of nitrite with sulfanilamide and N
      phenyl J-Acid system].
AB  - In the present article, compounds used in diazotizing-coupling reaction were
      selected. The conditions and methods of diazotizing-coupling chromogenic reaction
      were studied. A new method of diazotizing-coupling spectrophotometry with
      sulfanilamide(p-aminobenzene sulfonamide) and J-Acid series dye intermediates (N
      phenyl J-Acid, J-Acid, Di-J-Acid) to determine nitrite was developed. At room
      temperature, in the presence of potassium bromide, nitrous acid reacted with
      sulfanilamide in the medium of thin hydrochloric acid. Then diazonium salt
      reacted with N-phenyl J-Acid in the aqueous solution of sodium carbonate, forming
      coloured azo compounds. The apparent molar absorptivity was 4.63 x 10(4) L x mol(
      1) x cm(-1). The Beer's law was obeyed in the range of 0.003-0.7 mg x L(-1). The
      recoveries were in the range of 99.5%-101.6%. RSD was 2.1%. This method has been
      used for the determination of trace nitrite in the environmental water.

PMID- 17554926
TI  - [Microscopic raman imaging spectra of realgar and light-induced degradation
      products in realgar].
AB  - Light-induced degradation in realgar was studied by means of Raman spectroscopy.
      The result substantiated the following reaction: An additional S atom is inserted
      between the As atoms in the As4S4 molecule because As--As bonds are weaker than
      As--S bonds. It is likely that the resulting As--S--As molecule is too unstable
      to exist. Furthermore, an S atom in the As4S5 molecule is released from one of
      the equivalent As--S--As linkages in As4Ss which becomes the As4S4 molecular of
      pararealgar. After the As4S5 molecule is divided into an S atom (radical) and the
      As4S4 (pararealgar type) molecule, the free S atom is re-attached to another
      As4S4 (realgar type) molecule, reproducing an As4S5 molecule. The reproduced
      As4S5 molecule is again divided into an S atom (radical) and an As4S4
      (pararealgar type) molecule. This cycle whereby realgar is indirectly transformed
      into pararealgar via the As4S5 molecule is promoted by light and repeated during
      light exposure.

PMID- 17554927
TI  - [Research on raman spectra and energy transfer in Tm3+, Ho3+ single and co-doped
      YVO4 crystals].
AB  - Raman spectra of Tm3+ :YVO4, Ho3+ :YVO4 and Tm3+: Ho3+: YVO4 crystals were
      measured at room temperature by HRD-1 double grating monochromator, with the
      excitation laser beam were parallel and perpendicular to c axis, respectively.
      For the Ho3+: YVO4, it was found that the Raman spectrum excited by laser beam
      perpendicular to axis c is stronger than that by parallel excitation, and because
      488 nm laser was very close to the absorption peak of Ho3+, the competition
      between absorption and scattering results in the 475 cm(-1) Raman mode weakening
      and external mode widening. It was also found that the most probable phonon
      energy focused on the 880 cm(-1), which was brought about by the breathe mode of
      (VO4)3-, Like YAG, YVO4 is a kind of crystal with high phonon energy too.
      Comparing the luminescence of Tm3+ :YVO4 with that of Tm3+: Ho3+: YVO4, it was
      found that the intensity of Ho3+ 2.09 microm is about 4/5 of that of Tm3+ 1.85
      microm, which means the sensitization efficiency of Tm3+ to Ho3+ was as high as
      up to 80%, and since the overlap between the luminescence of Tm3+ with the
      absorption of Ho3+ is quite small, the radiative energy transfer between them was
      very less possible, and most probability, this process was via the nonradiative,
      phonon-aided cross-relaxation between Tm3+ and near resonance energy transfer
      between Tm3+ and Ho3+.

PMID- 17554928
TI  - [Determination of trace elements in drinking water of Kashin-Beck disease (KBD)
      affected and non-affected areas in Tibet by ICP-AES].
AB  - Trace elements (Cu, Zn, Fe, Ca, Mg, Mn, Al, K, Ba, P, Sr, Cd, V, Cr, Ni, Pb and
      Co) concentrations in the drinking water of KBD-affected and non-affected areas
      were measured using ICP-AES. The RSD of this method was between 0.80% and 2.83%,
      and the analytical results of the reference samples were consistent with the
      certified values. The method was simple and accurate. The results indicated that
      there is an obvious difference in trace elements concentrations between KBD
      affected areas and non-afffected areas. The results provided a scientific
      theoretical basis to improve the conditions of drinking water in KBD-affected
      areas in Tibet.

PMID- 17554929
TI  - [Flame atomic absorption spectrometric determination of copper and lead in beer
      after preconcentration using a rapid coprecipitation technique with 8
      oxyquinoline].
AB  - A method was proposed for the determination of trace copper and lead in beer with
      flame atomic absorption spectrometry after preconcentration of copper and lead by
      rapid coprecipitation technique with 8-oxyquinoline-Mg(II) using manganese as an
      internal standard at pH 9. The standard addition recovery of lead is between
      97.6%-103.0%. The detection limit is 6.28 x 10(-3) microg x mL(-1) for copper and
      2.26 x 10(-2) microg x mL(-1) for lead when the sample volume is 100 mL. The
      effect of matrix can be overcome by the method and the results are satisfying.
      The method proposed here is rapid and has good reproducibility.

PMID- 17554930
TI  - [Preconcentration of trace Pd (II) on crosslinked chitosan and determination by
      graphite furnace atomic absorption spectrometry].
AB  - A novel crosslinked chitosan(CCTS) not dissolved in acidic or alkaline solutions
      was synthesized by the crosslinking reaction of chitosan (CTS) with crosslinking
      agent (3-chloro-1,2-epoxypropane). The adsorption capability of Pd(II ) by CCTS
      was studied at different pH value. The results showed that the adsorption
      efficiency was above 98% after preconcentration for 20 minutes when pH values
      were 1-4. The effects of preconcentration time, dosage of CCTS, adsorption
      capacity of CCTS, sample volume, coexistent elements, and elution of Pd(II) were
      investigated. The mechanism of adsorption of CCTS for Pd(II) was discussed. A
      novel method for the preconcentration and separation of trace Pd(II) with
      crosslinked chitosan (CCTS) and its determination in water by graphite furnace
      atomic absorption spectrometry has been developed. The detection limit (3sigma,
      n=8) was 0.143 microg x L(-1), the relative standard deviation(RSD) was less than
      5.47%, and this preconcentration method was used to detect Pd(II) in lake water
      and sea water with recoveries of 92%-96%. It also can be used to recycle Pd(II).

PMID- 17554931
TI  - [Spectrometric determination of the content of nutritional elements in fruits of
      different red pear varieties].
AB  - A study was carried out on the contents of nutritional elements such as K, Fe,
      Zn, Ca, Cu, Mg and Mn in three different red pear varieties, namely Meirensu,
      Hongsucui and Mantianhongs, by flame atomic absorption. The results indicated
      that the linear relationships for different elements within the limits of working
      curves are good, and the range of recovery is 98%-104%, hence showing that the
      results asre satisfactory. There are abundant nutritional elements in fruits of
      the three different red pear varieties, meaning that they all have a relatively
      high nutritive value. In fruits of the three red pear varieties, the content
      sequence of different nutritional elements was found to be K>Fe>Zn>Ca>Cu>Mg>Mn.
      In fruits of the three different red pear varieties, the content sequence of K,
      Zn, Mg and Mn was Meirensu> Hongsucui>Mantianhong; the content sequence of Fe and
      Cu was Hongsucui>Mantianhong>Meirensu; and the content sequence of Ca was
      Mantianhong>Hongsucui> Meirensu; and the total content sequence of seven
      nutritional elements was Hongsucui>Meirensu>Mantianhong.

PMID- 17554932
TI  - [Study on ZnTe (Znte:Cu) polycrystalline films by XPS].
AB  - ZnTe and ZnTe: Cu polycrystalline films were fabricated by means of co
      evaporating at room temperature. The relationships between conductivity of the
      films and temperature were measured. Chemical compositions of ZnTe and ZnTe: Cu
      polycrystalline films were obtained by using XPS, and the changes of chemical
      composition before and after anneal were analyzed. The results showed that the
      conductivity of ZnTe rose linearly with the temperature, and Te was enriched on
      the margin of every sample's surface; With the rise in temperature, the
      conductivity of ZnTe: Cu films became abnormal, the oxidization of Te became very
      obvious and Zn diffused from the bulk to the surface. The composition became more
      uniform and all peaks became stronger. Carrier concentration caused by CuxTe
      appeared, resulting in the abnormal relationship between conductivity of the
      films and temperature.

PMID- 17554933
TI  - [Studies of spectra classification based on kernel covering algorithm].
AB  - A kernel based covering algorithm, called the kernel covering algorithm (KCA), is
      proposed for the classification of celestial spectra. This algorithm is a
      combination of kernel trick with the covering algorithm, and is used to extract
      the support vectors in feature space. The experiments show that the
      classification result based on KCA is a little less than that based on SVM.
      However, KCA only involves the distance computation without the need to solve the
      quadratic programming problem. Also, KCA is insensitive to the width of gauss
      window. Although KCA has a comparable classification performance with the
      covering algorithm, it changes the distance between samples in feature space by
      the nonlinear mapping such that the distribution of samples is more adaptable to
      classify. Therefore, the number of KCA's resulting support vectors is
      significantly smaller than that of the covering algorithm.

PMID- 17554934
TI  - [A study on the outlier mining system for LAMOST spectra].
AB  - To find unknown celestial bodies is one of main goals in mankind's universe
      exploration, and outlier mining is a kind of effective way of finding unknown
      celestial bodies from mass spectrum data. In the present work, using VC++ and
      Oracle9i as development tools, an outlier mining system for star spectra is
      designed and realized, and its software architecture and function modules are
      outlined. At the same time, the system's key components such as star spectrum
      data preprocessing based on median filters, clustering of star spectrum data
      based on distance, outlier mining of star spectrum data based on distance support
      and three-dimensional visualization of star spectrum outlier based on PCA, are
      elaborated. The preliminary experimental results based on SDSS star spectrum data
      show that the system is workable for outlier mining of celestial body spectrum
      data, and a new kind of effective way of finding unknown and peculiar celestial
      body spectrum data.

PMID- 17554935
TI  - [The novel combined x-ray image intensifier].
AB  - By combining X-ray imaging technology and low light level imaging technology, the
      authors' research group designed the novel combined X-ray image intensifier.
      Different from the imported conventional one, it is an X-ray screen lens coupled
      with a brightness intensifier, and is a non-vacuum device. In this paper, the
      novel combined X-ray image intensifier is described in terms of its structure,
      imaging principle and imaging performance, and the comparisons of the structure,
      imaging principle and imaging performance between the novel combined one and the
      conventional one are given in detail. It is clear that the conventional medical
      tube is a little better than the novel combined one in imaging performance,
      whereas the novel combined one has a very high cost effectiveness and the
      satisfied imaging performance, and moreover, the quality disparity between the
      novel combined one and the imported medical one is being shortened. The novel
      combined one meets the X-ray imaging standard in many science and research fields
      and is convenient to be accepted by the usual users and has wide application
      fields such as industrial detection, nondestructive test and airport security
      check.

PMID- 17554936
TI  - [IR thermal-emitter based photoacoustic spectrometer for gas detection].
AB  - An IR thermal-emitter based photoacoustic spectrometer for gas detection was
      developed. The function and structure of the hardware and the software for the
      spectrometer were presented. Based on the analysis of spectral characteristics of
      the IR source, the integrated absorption coefficients of absorption gases at
      different absorption bands were compared, thus the optimum parameters of the
      photoacoustic cell and the IR filters were determined. The experimental results
      showed that the detection limits of 1.6 x 10(-6), 4.5 x 10(-6) and 4.0 x 10(-4)
      for CO, NO and H2S gases could be obtained respectively. The repeatability and
      linearity were also tested for CO gas in the concentration range of 0-987 x 10(
      6), and the results are fairly satisfactory. In addition, many other kinds of
      gases can be measured with the same spectrometer, simply by adding some
      corresponding IR filters.

PMID- 17554937
TI  - [Development of a micro-infrared spectrometer based on pulse infrared light
      source and two-double light route].
AB  - A novel micro infrared spectrometer was designed which is different from
      traditional grating scanning one. This micro spectrometer introduced an uncooled
      infrared detector LiTaO3 with high sensitivity and small volume, and a MEMS
      pulsed infrared light source was adopted as emitter and chopper, which threw off
      traditional mechanical chopper. Combined with the design of a two-double light
      route, the volume of micro spectrometer was made even smaller. Primary results
      show that the design method of micro-infrared spectrometer is feasible, the
      wavelength range of instrument is wide, from 2000 to 5000 nm, and spectrum
      bandwidth is about 45 nm, which can be used for the sample analysis, such as
      plastic films, biologic liquid, environmental gas and so on.

PMID- 17554938
TI  - How aggressively should cholesterol targets be pursued?

PMID- 17554939
TI  - Smell disorders and dysosmia.

PMID- 17554940
TI  - Techniques used for assessing the sense of smell.
AB  - Assessment of the sense of smell is a challenging clinical investigation.
      Although a wide range of tests are available, many are modifications of tests
      designed more than 20 years ago. This article describes the smell tests that are
      available, and consider smell assessment after nasal surgery.

PMID- 17554941
TI  - The management of olfactory disorders.
AB  - Disorders of olfaction affect quality of life and their significance are
      underestimated. Investigation and diagnosis can help in the early implementation
      of rehabilitative measures and also in recognizing those forms of olfactory
      disorders that are potentially treatable.

PMID- 17554942
TI  - The limping child: a clinical approach to diagnosis.
AB  - Acute limp in childhood is associated with considerable anxiety for parents and
      clinicians alike. It can be a diagnostic challenge in the uncooperative child and
      any delay in diagnosis can result in significant morbidity and even mortality. A
      thorough clinical evaluation is of utmost importance. This review revisits the
      clinical assessment of a limping child and explores the relevant literature.

PMID- 17554943
TI  - Optimizing decisions about treatment in locally advanced prostate cancer.
AB  - The decision-making process for the management of locally advanced prostate
      cancer is very complex for both patients and health-care professionals. The
      Vitality Index can be used to help tailor therapy approaches to match the
      individual lifestyle needs of patients.

PMID- 17554944
TI  - Abdominal injuries.

PMID- 17554945
TI  - The clinical anatomy of lumbar puncture.

PMID- 17554946
TI  - Effectively communicating a diagnosis of Parkinson's disease.

PMID- 17554947
TI  - A perspective on the current issues in the diagnosis of Parkinson's disease.
AB  - The National Institute for Health and Clinical Excellence published guidelines
      for the management of Parkinson's disease in 2006. This article summarizes the
      key diagnostic recommendations of the guidelines, and gives a personal view of
      current barriers to their implementation and how these might be overcome.

PMID- 17554948
TI  - Publish or perish: how to secure your first publication.

PMID- 17554949
TI  - Team working: a guide for the foundation year doctor.

PMID- 17554950
TI  - Forearm fractures.

PMID- 17554951
TI  - Management of atrial arrhythmias 3: paroxysmal atrial fibrillation.
AB  - This is the third in a series of four practical articles highlighting the
      important management steps for non-cardiologists and non-cardiac
      electrophysiologists dealing with patients with atrial fibrillation and common
      atrial flutter. This article will deal with care pathways and management
      principles for paroxysmal atrial fibrillation.

PMID- 17554952
TI  - Psoriasis: maximizing topical treatment concordance.
AB  - Psoriasis is one of the most commonly occurring skin conditions in the UK. It is
      a chronic inflammatory disease and therefore psoriatic patients are predisposed
      to developing other inflammatory conditions such as cardiovascular disease. The
      management of such patients increasingly involves other specialties. A basic
      knowledge of available topical treatments is essential in improving overall
      patient concordance.

PMID- 17554954
TI  - How hospital trainees prefer to learn.
AB  - Formal postgraduate training curricula must be delivered effectively and
      efficiently. This survey identifies the learning situations trainees prefer and
      the elements that constitute a learning experience. Greater understanding of
      these factors may help tutors plan more effective teaching and learning
      opportunities.

PMID- 17554955
TI  - Unusually positioned abscesses of the head and neck following suppurative otitis
      media.

PMID- 17554956
TI  - Chilaiditi's syndrome.

PMID- 17554957
TI  - Bacterial meningitis resulting in visual impairment and panhypopituitarism.

PMID- 17554958
TI  - Life-threatening fungal meningitis-ventriculitis secondary to vaginal
      candidiasis.

PMID- 17554960
TI  - Investment risk.

PMID- 17554959
TI  - Foot ecchymosis sign: a valuable diagnostic sign with therapeutic implications.

PMID- 17554961
TI  - NICE and dementia treatment guidance.

PMID- 17554962
TI  - The use of vasopressors in pulmonary hypertension on the intensive care unit.

PMID- 17554963
TI  - [Bioequivalence studies of pharmaceutical preparations].
AB  - Bioequivalence studies are very important for the development of a pharmaceutical
      preparation in the pharmaceutical industry. Their rationale is the monitoring of
      pharmacokinetic and pharmacodynamic parameters after the administration of tested
      drugs. The target of such study is to evaluate the therapeutic compatibility of
      tested drugs (pharmaceutical equivalents or pharmaceutical alternatives). The
      importance of bioequivalence studies is increasing also due to the large growth
      of the production and consumption of generic products. Generic products represent
      approximately 50 % of the whole consumption in many European countries and USA.
      The search output of bioequivalence study is together with the pharmaceutical
      quality data of medical product one of the main part of the registration file
      submitted to a national regulatory authorities. The registration of generic
      products does not demand complicated and expensive clinical study contrary to
      original product. The comparison of the original and the generic product via
      bioequivalence study is suggested as sufficient. The aim of this article is to
      provide to a medical public a summary about the types of bioequivalence studies,
      their range, rules of their practise and let them gain their own attitude to this
      question.

PMID- 17554964
TI  - [Cognitive functions impairment in diabetes mellitus patient].
AB  - An increased research interest in the relation between diabetes mellitus and
      dementia or deterioration of cognitive functions has been recently noticed. The
      relatively rich scientific literature in this topic shows that diabetes mellitus
      itself can cause an impairment of cognitive functions regardless patient's age or
      the fact whether he has type 1 or type 2 diabetes mellitus. Type 1 diabetes
      mellitus leads to a psychomotor retardation while type 2 diabetes mellitus tends
      to be associated with impaired storage of new information. The exact mechanism
      through which diabetes impairs cognition has not been explained sufficiently yet,
      but several hypothetical mechanisms which might explain the relation between
      diabetes and impaired cognition have been proposed. To explain the
      etiopathogenetic mechanisms underlying the relation between diabetes and
      dementia, further research, especially research focused on process clinical
      imaging studies or clinical-pathological studies is necessary. As far as clinical
      practice is concerned, it is important to bear in mind that prevention, timely
      diagnosis and optimum treatment of diabetes may help to reduce incidence of
      dementia or cognitive functions' impairment.

PMID- 17554965
TI  - [Stem cells, stem cell therapy, and ethical problems of medicine].
AB  - Common denominator of many philosophic approaches to the problem of using human
      embryos in medicine is the statement that it is "a full-value human subject that
      deserves respect as an adult human being". It has a defined identity in which it
      starts its own coordinated gradual development. Therefore, it is not just a
      simple cluster of cells. Integrity or holistic properties of a new quality of
      cells that, as a whole, represent an early embryo, and in fact are not a cluster
      of pre-embryonic "structural" parts or a sum of cells etc. They have theirs own
      evolution, previously inherently encoded, but not precisely predestined. In other
      words, only autointegrity alone in evolution, inherence as a part of
      predetermination in evolution of embryo, is not able to exist as a unit "alone".
      Human foetus since the first moments of its existence goes through many
      qualitative (externally or internally determined) transformations before it
      becomes a respectable human being. It is possible to say that medicine, as many
      times before, is now coming to a stage when axiologic values, ethical directives
      or moral feelings of its subjects and human objects proved in the past, are no
      more relevant at present. Therefore, medicine has no other alternative than an
      active approach to study this problem from all philosophical, biological and
      medical aspects to evolutionize itself in this new dimension. In this paper some
      of these questions are discussed and some ways of forming the ethics in
      therapeutic use of stem cells are presented.

PMID- 17554966
TI  - [Present view on the spinal haemangioma].
AB  - Ethiopathogenesis, diagnostic and treatment of spinal haemangioma remains
      suggestive topic not only for surgeons. The development of diagnostic imaging
      methods allows more precise evaluation of the pathology and optimal therapeutic
      planning. We have many therapeutic modalities: selective embolisation,
      radiotherapy, vertebroplasty, alcohol ablation and surgery. It depends on
      radiologic findings and clinical status which of them is used. The treatment of
      emergent compression is still the domain of surgeon. In the therapy of
      haemangiomas causing local pain, we prefer less invasive procedures. The
      interdisciplinary cooperation is required for the successful treatment.

PMID- 17554967
TI  - [Phototoxic reaction after the systemic administration of antimicrobial drugs].
AB  - Several systemically administered drugs with antimicrobial effect have
      undesirable phototoxic effects. This group includes some antibiotics (e.g.,
      tetracycline, fluorochinolons, and also macrolids), sulphonamides and related
      chemotherapeutics, antimycotics, tuberculostatics, antiviral drugs and
      antimetabolites. Doctors should know the phototoxic effect of those drugs in
      advance, because of the possible time shortage they might have when they
      prescribe the drugs. The first condition is to obtain the relevant personal
      history data, and in case the phototoxic reaction develops, to terminate the
      unsuitable drug, to change it for another, to administer antihistaminics,
      sometimes corticoids, prevent exposition to sun, and administer local anti
      inflammatory dermatological drugs.

PMID- 17554968
TI  - [Problems of regulation of breathing].
AB  - Knowledge about the regulation of breathing has pronounced clinical consequences.
      In the review the concepts of control and regulation of breathing are defined.
      Regulation based on the chemical feed back is well documented. Apart from that,
      attention is paid to unproven, hypothetical regulations. Among them, the
      regulation of the breathing pattern and that of functional residual lung capacity
      are of especial interest. Not less important is the cortical or volitional
      regulation of breathing, which is so far almost unexplored. An important problem
      represents abnormalities of the regulation of breathing. The disturbance can
      either follow a damage of the system of regulation, or it can be the result of
      conflict of priorities among the individual regulatory systems. Also this area is
      built on hypotheses which need experimental and clinical verification. Hand in
      hand with it goes the problem of regulation of breathing in disease. In
      conclusion, problems for elucidation are summarized.

PMID- 17554969
TI  - [Conjugated linoleic acid--the dietary supplement in the prevention of
      cardiovascular diseases].
AB  - Conjugated linoleic acid is an integral term for the mixture of positional and
      geometrical isomers of the octadecadienoic acids, whose two double-bonds are
      separated with one single-bond. The most common isomers are cis-9, trans-11, and
      trans-10, cis-12. Conjugated linoleic acid is present in the food namely in the
      red meat and dairy products which the contemporary dietary recommendations tend
      to limit. Those limitations should be compensated with dietary supplements.
      Experimental studies have shown the positive effects of the conjugated linoleic
      acid in the regulation of the body weight, in the reduction of risk factors of
      cardiovascular diseases, for improvement of immunity and in the reduction of
      risks of the development of some carcinomas. Those studies have also considered
      different effects of individual isomers. Stimulating results of experimental
      studies represent the basis of the research in human medicine, where the results
      are not so unequivocal. Studies are difficult to compare owing to the different
      arrangement (number of persons, daily dose, length of administration). Positive
      effects on the adiposity and proportion of the visceral fat was observed after
      the long-term administration, however, mechanism of the effect has not been
      explained yet. It can be due to the inhibition of lipoprotein lipase, rise of
      carnitine-palmitoyl transferase activity, induction of adipocyte apoptosis,
      modulation of PPARgamma effects. For the explanation some new long-term studies
      with defined clinics will be necessary. Present view on the indication of the
      conjugated linoleic acid administration from the point of complex modulation of
      risks of the development of cardiovascular and metabolic diseases is
      inconsistent.

PMID- 17554970
TI  - [Transcription factor Egr-1 in cardiovascular biology].
AB  - The zinc finger transcription factor Egr-l plays an important role in
      cardiovascular biology. While binding complementary motifs on DNA in the target
      genes, Egr-1 either increases or decreases proteosynthesis of many
      proinflammatory and antiinflammatory mediators. In physiologic circumstances,
      these mediators support healing and regeneration of damaged tissue, mainly by
      conducting angioneogenesis. In pathologic circumstances these same mediators take
      an active part in promoting tissue injury. The participation of the transcription
      factor Egr-1 in the pathogenesis of atherosclerosis can be traced from the
      initial phases with the generation of foam cells as far as the onset of acute
      cardiovascular or cerebrovascular ischemic events. At the same time,
      transcription factor Egr-1 presents a would-be linker at the level of which
      converge many seemingly heterogenous atherogenic risk factors such as
      hyperlipidemic disorders, untoward rheologic changes of blood flow often
      encountered in arterial hypertension or various infectious agents, with Chlamydia
      pneumoniae belonging to the most deeply investigated ones. Protective effects of
      the known anti-atherogenic factors, such as the endogenous antiinflammatory
      cytokine interleukin-10 or the "pleiotropic" effects of statins can be, at least
      in part, explained by their inhibitory influence on the activities of the
      transcription factor Egr-1.

PMID- 17554971
TI  - [Incidence, diagnostics and therapy of the lung cancer in the Czech Republic in
      2003].
AB  - Lung cancer epidemic has not ended. According to the data on the incidence and
      mortality in the Czech Republic it is obvious that both parameters decline in
      males; the rise in women probably ends. According to the present epidemiological
      parameters the number of new cases is still very high. Number of adenocarcinomas
      is slightly rising. No improvement has been achieved in the early diagnostics of
      TNM stage I and II, which are diagnosed in less than 21 %. It brings low number
      of indications for resection therapy, which in 2003 achieved 10.8 % for men and
      10.1 % for women. Positive appears the higher number of verified tumours (72 % in
      men and 69 % in women) and the higher percentage of those who survived over 5
      years (6.3 % in men and 9.4 % in women) in comparison with the situation 10 years
      earlier. The presented paper describes regional differences in the incidence of
      lung carcinoma (apparent gradient between the western and eastern part of the
      country) and the promptness of the diagnostics and the treatment indications.

PMID- 17554972
TI  - [Study of the eosinophilic inflammation activity in bronchial asthma].
AB  - BACKGROUND: Bronchial asthma is a chronic inflammatory disease of the respiratory
      tract where variety of cells plays a role, particularly mast cells, eosinophils
      (Eo), and T lymphocytes. At present, there is no clear-cut clinical or laboratory
      parameter to monitor the activity of this disease. Our study was designed to
      examine and compare serum eosinophilic cationic protein (S-ECP) levels, plasma ET
      1 (P-ET) levels and percentage of eosinophils with CD44 (EoCD44) in paediatric
      asthmatic patients. METHODS AND RESULTS: In our study, a group of 97 atopic
      children with persisting mild asthma, had a detailed analysis of their personal
      history. In addition, S-ECP, P-ET, EoCD44, eosinophil blood count (Eo) and serum
      levels of IgE(S-IgE) in peripheral blood were determined. Subsequently, children
      were treated with montelukast (singular), a leukotriene receptor antagonist for a
      period of three weeks (montelukast tablets in a dose of 5 mg once a day). A
      second S-ECP, P-ET, EoCD44 were determined in the interval of 3 months from the
      first collection. In 97 asthmatic children a correlation between P-ET and EoCD44
      (p=0.002; r= -0.5) were found. CONCLUSIONS: Our follow-up study surprisingly
      confirmed a correlation between P-ET and EoCD44. The lower percentage of EoCD44
      in peripheral blood in asthmatic children is due to Eo inflammation activity and
      attests the massive Eo invasion into the airways. The determination of
      combination - S-ECP, P-ET, EoCD44 - provides an indirect evidence of the multiple
      features of Eo inflammation.

PMID- 17554973
TI  - [Composition of the nonesterified fatty acids and lipid peroxidation in metabolic
      syndrome].
AB  - BACKGROUND: Composition of the nonesterified fatty acids in plasma in metabolic
      syndrome patients and in other syndromes of insulin resistance is altered. Fatty
      acid profile in plasma is related to the composition of dietary fat and to the
      metabolic changes of fatty acids, e.g. to de novo lipogenesis, beta-oxidation and
      conversion accompanying the oxidative stress. The aim of the work was to study
      the fatty acid composition in the major plasma lipid classes in relation to the
      insulin resistance, to some polymorphisms of candidate genes with activity
      related to insulin resistance, and to the lipoprotein composition and parameters
      of lipid peroxidation. METHODS AND RESULTS: 95 patients with metabolic syndrome
      (56 M/39 F) and 195 healthy persons (99 M/96 F) were included into the cohort.
      Basic clinical data, parameters of glucose homeostasis, lipid concentration in
      plasma and conjugated diens in LDL were determined. Fatty acids were detected by
      capillary gas chromatography. Polymorphisms of apolipoprotein E, intestinal
      isoforms of fatty acid binding protein (Ala54Thr) and y-2 isoforms of peroxisomal
      activated receptor (Alal2Pro) were analyzed using combination of polymerase chain
      reaction methods and by the detection of polymorphisms of the restriction
      fragment length. Persons with metabolic syndrome had higher concentrations of CRP
      and conjugated diens in LDL. In all lipid classes we proved a decreased
      concentration of n-6 polyunsaturated fatty acids and an increase of unsaturated
      fatty acids. From all the acids, the only significant was the decrease of linolic
      acid concentration and the increase of palmitic and palmitoyl acids. Results
      showed an increase of delta 9 palmitic acid desaturase activity, delta 6 linolic
      acid desaturase and elongase activity. Concentration of conjugated diens in LDL
      inversely correlated with linolic acid. Clinical or laboratory parameters and
      homozygotic combination of polymorphism studied were not mutually related.
      CONCLUSIONS: Changes in the profile of fatty acids during the metabolic syndrome
      results from the elevated lipogenesis and from the higher level of oxidative
      stress.

PMID- 17554974
TI  - [Prospects of body composition analysis by bioimpedance method in children].
AB  - BACKGROUND: Increases in juvenile overweight and obesity have emphasized the
      importance of accurate and accessible body composition (BC) assessment, namely
      for the monitoring, prevention and treatment. Bioimpedance analysis seems to be
      one of the simple, safe, and inexpensive methods for assessment of the body
      composition in paediatric subjects METHODS AND RESULTS: Three-thousand-twelve
      children aged 6-14 years (1611 - 53.5 % boys, and 1401 - 46.5 % girls) were
      evaluated BC using mono frequency and multi-frequency bioimpedance analyser with
      adapted prediction equation for Czech children. In both genders %BF decreased
      significantly with age (r = -0.698 in boys and r = -0.681 in girls, both
      p<0.0005). Linear regression analysis showed a significant positive relationship
      between %BF measured with BMI %BF(%)= 0.921*BMI(kg.m(-2)) -4.292, r = 0.858, r(2)
      = 0.736, SEE = 1.22 % in boys, and in girls %BF(%) = 1.284*BMI(kg.m(-2)) - 6.906,
      r = 0.903, r(2) = 0.815, SEE = 1.05 %, p<0.0001 in both cases. CONCLUSIONS: BIA
      method is a useful method for detecting BC in children and can be accepted as a
      precise tool for measuring of BC in epidemiological studies in children. The
      decisive role for the use of this method has the population oriented prediction
      equation and the subject's hydration state.

PMID- 17554975
TI  - [The assessment of body composition using DEXA in patients with thyroid
      dysfunction].
AB  - BACKGROUND: Disturbed thyroid function is accompanied with weight changes in most
      of patients. Less is known how the therapy of hyperthyroidism and hypothyroidism
      influences their body composition. METHODS AND RESULTS: We investigated 18
      persons with newly diagnosed hyperthyroidism (group I), 15 persons with newly
      diagnosed hypothyroidism (group II), 22 persons with long-lasting well-controlled
      primary hypothyroidism (group II) and 17 persons with history of cured
      hyperthyroidism (group IV). Body composition, including percentage of body fat,
      was examined with Dual energy absorptiometry method (DXA; GE Lunar prodigy).
      There was no significant difference in age, BMI, and % of body fat between
      groups. Group I had mean levels of free T4: 43.1+/-20.1 pmol/L, and TSH 0.03+/
      0.05 mU/L. Mean values of TSH 28.55+/-20.64 mU/L and free T4 5.94+/-2.27 pmol/L
      were in accordance with the diagnosis of untreated hypothyroidism in group II.
      Thyroid function in groups III and IV was within normal limits. The mean weight
      gain in group I was 3.9 kg and their BMI increased from 25.78+/-3.73 kg/m(2) to
      27.36+4.03 kg/m(2) after the therapy (p=0.023). BMI has not changed significantly
      in group II after the normalization of thyroid function, nor in group II and III.
      A significant parallel increase in the total body fat (26737+/-6993 g vs. 31277+/
      8735 g), (p=0.0078) as well as in lean mass (43936+/-9886 g vs 51065+/-9501 g)
      (p= 0.0156) was observed only in group I after therapy. There was no increase in
      percentage of body fat (38.04+/-8.6% vs.38.0+/-9.8%) (NS). The body composition
      did not changed in the other patients treated during the follow-up. CONCLUSIONS:
      Normalization of thyroid function of newly diagnosed hyperthyroid patients caused
      the parallel increase in their fat mass and lean body mass, assed with DXA.
      Percentage of fat mass did not change significantly after the treatment.
      Correction of hypothyroidism did not lead to the body composition changes;
      patients did not show any weight loss either.

PMID- 17554976
TI  - [Is prescription of physical activity a part of health care in civilization
      disorders? Results of questionnaire study in medical doctors].
AB  - BACKGROUND: Low level of physical activity is an independent risk factor of
      civilization disorders. Intervention for increasing physical activity has been
      for generations mentioned in health care. Because of low adherence of the
      population to those general appeals it is necessary to improve radically the
      knowledge of health professionals about individual exercise prescription. The aim
      of this study was to analyze approach of medical doctors in this particular
      dilemma. METHODS AND RESULTS: A questionnaire was distributed at postgraduate
      courses for medical doctors. Data from doctors of different specializations were
      summarized (N=657, from which 458 were females, i.e. 69,7 %, mean age=38,8+/
      9,74). 96,4 % of doctors stated that they recommend exercise to their patients
      though only up to 23,4 % of them are regularly asked by their patients about the
      exercise. Concrete (type, intensity, duration and frequency) or individually
      tailored recommendation give 66,2 %, or 62,6 % of doctors respectively. Most
      respondents (56,0 %) also recommend a consultation of another specialist (mostly
      rehabilitation doctor and physiotherapist). Majority of addressed professionals
      shows that current medical education structure does not enable adequate
      prescription of physical activity without the help of specialist. CONCLUSIONS:
      Study showed a positive attitude of medical doctors to exercise prescription.
      However, information about the need of individualized prescription and knowledge
      about possibilities of exercise therapy in particular regions should be
      increased.

PMID- 17554977
TI  - [Twenty five years since information on a new nosological unit AIDS was
      published].

PMID- 17554978
TI  - [Stress cardiomyopathy].
AB  - Stress cardiomyopathy is a disease characterized by an acute systolic dysfunction
      of the left ventricle of the heart which is fully reversible and does not affect
      basal segments of the left ventricle. It is not accompanied by significant
      stenoses of the coronary arteries and it is caused by a preceding stressful
      situation. This article provides an overview of the ethiopathogenesis, diagnostic
      and therapeutic methods. Finally, we present a case report of our patient who
      suffers from a rare form of the midventricular type of stress cardiomyopathy.

PMID- 17554980
TI  - [Usefulness of FDG-PET for the diagnosis of postoperative recurrence of lung
      cancer].
AB  - No standardized postoperative follow-up strategy has been established for lung
      cancer patients, although CT and tumor markers are often employed. We conducted a
      retrospective study evaluating fluoro-2-deoxyglucose positron emission tomography
      (FDG-PET) for the diagnosis of postoperative recurrence of lung cancer. We
      evaluated 28 patients with suspected postoperative recurrence of lung cancer, who
      underwent FDG-PET between July 2004 and November 2005. Of these, 15 showed
      positive PET finings. Recurrence of lung cancer cases confirmed in 14 of these
      and the remaining case showed a postoperative scar. Thirteen patients with no
      findings on PET scan have demonstrated no evidence of recurrence during follow-up
      periods between 10 to 23 months. The negative predictive value was therefore
      100%. FDG-PET in addition to chest CT and tumor markers for the diagnosis of the
      postoperative recurrence of lung cancer is considered to be beneficial in terms
      of avoiding excessive radiation exposure and limiting medical costs, but further
      evaluation in more patients is necessary.

PMID- 17554981
TI  - [Coexisting lung cancer and active pulmonary mycobacteriosis].
AB  - We reviewed 72 patients with coexisting lung cancer and pulmonary
      mycobacteriosis, and discuss the features and transition of these coexistent
      cases. There were 56 pulmonary tuberculosis (PTB) cases and 16 non-tuberculous
      mycobacteriosis (PNTM) cases, 62 men and 10 women, with a mean age of 69 years.
      In 43 cases, both diseases were concurrently detected, lung cancer was first
      detected in 19 cases, and mycobacteriosis was first detected in 10 cases. The
      frequency of lung cancer in cases with active pulmonary mycobacteriosis was 1.2%.
      Pulmonary mycobacteriosis was characterized by Type II (40 cases) and Spread 2
      (42 cases) on chest X-rays; the most frequent histologic type of lung cancer was
      squamous cell carcinoma (32 cases) and most were stage III-IV cases (57 cases).
      After PTB treatment, the negative conversion rate of sputum cultures in both the
      concurrently detected group and the group in which lung cancer was initially
      detected was 56% within one month and 94% within 2 months. For the treatment of
      lung cancer, 33 cases received supportive care, 13 patients underwent resection
      and 17 received chemotherapy or chemoradiotherapy. In PNTM cases, both lung
      cancer and pulmonary mycobacteriosis showed a slight state compared to those in
      PTB cases, and in the group in which lung cancer was initially detected, both
      diseases were more advanced or severe than those in the concurrently detected
      group or in the group in which mycobacteriosis was initially detected. The rate
      of coexisting lung cancer and pulmonary mycobacteriosis was unchanged at 1-2%,
      and the incidence of stage IV lung cancer cases has increased recently.
      Coexisting lung cancer and pulmonary mycobacteriosis is an important condition in
      respiratory disease in Japan. Physicians should be aware of the possibility of
      PTB coexisting with lung cancer.

PMID- 17554982
TI  - [Pneumocystis carinii pneumonia in a patient with hyper-IgE syndrome].
AB  - A 15-year-old girl with abnormal findings detected on a medical check-up chest x
      ray film was admitted to our center. High-resolution computed tomography,
      performed upon hospitalization, demonstrated panlobular nodular darkening in left
      lung fields, and an expanding, blended, map-like darkening near the pleura. Since
      a Grocott stain-positive cyst was confirmed histopathologically by transbronchial
      lung biopsy, the patient was given a diagnosis of Pneumocystis carinii pneumonia.
      Drug therapy was initiated with sulfamethoxaxole trimethoprim (Baktar), and on
      the 58th day, chest CT confirmed that the darkening observed at admission had
      virtually disappeared. Underlying diseases, such as AIDS, malignant lymphoma and
      secondary immunodeficiency caused by immunosuppressive agents or
      adrenocorticosteroids, were excluded as the cause of P. carinii pneumonia based
      on clinical/laboratory findings. Under the suspicion of the possibility of
      primary immunodeficiency, various immunological competence tests were performed.
      However, no abnormal findings indicating cell-mediated immunity, humoral
      immunity, complement immune function, neutrophil phagocytic capacity, or
      bactericidal capacity were recognized. Since significant increase of serum IgE
      suggested hyper-IgE syndrome, IgE antibody specific to Staphylococcal enterotoxin
      A and B, and the exotoxins of Staphylococcus aureus were measured with positive
      results. Since all three diagnostic criteria for hyper-IgE syndrome (i.e., high
      serum IgE values, positive IgE antibody specific to Staphylococcal enterotoxin
      and recurrent infection) were fulfilled, hyper-IgE syndrome was diagnosed. This
      is a rare case of hyper-IgE syndrome as a result of P. carinii pneumonia.

PMID- 17554983
TI  - [A case of lymphangioleiomyomatosis found due to chylous ascites, pleural
      effusion and pelvic lymphadenopathy].
AB  - We report a case of lymphangioleiomyomatosis, complaining initially of abdominal
      distension due to massive chylous ascites. The patient was a 28-year-old woman in
      whom abdominal ultrasound had strongly suggested the existence of both pelvic
      lymphadenopathy and massive ascites, the latter subsequently turning out to be
      chylous. Pelvic lymph node biopsy yielded a diagnosis of
      lymphangioleiomyomatosis. High-resolution computed tomography (HRCT) of the chest
      showed no remarkable findings except for very few cystic changes in the lung
      parenchyma. Pulmonary function had remained normal except for a temporary
      constrictive pattern when chylous pleural effusion developed. No airflow
      obstruction was detected on pulmonary function tests. Although
      lymphangioleiomyomatosis is often associated with pulmonary symptoms, we should
      bear in mind the possibility of lymphangioleiomyomatosis even in the absence of
      such symptoms when facing any woman of child-bearing age with abdominal chylous
      ascites of unknown etiology.

PMID- 17554984
TI  - [Large cell neuroendocrine carcinoma of the lung incidentally found at surgery
      for pulmonary aspergillosis].
AB  - We report a 56-year-old man with pulmonary large cell neuroendocrine carcinoma
      (LCNEC) incidentally found at the surgery for pulmonary aspergillosis. In 1991,
      an abnormal chest radiographic shadow was found on a mass screening. A diagnosis
      of pulmonary aspergillosis was made by bronchoscopic examination. The patient was
      then followed up without treatment. He had hemoptysis in 2005, and was referred
      to our hospital. Chest CT scan revealed a cavitary lesion with an air crescent
      sign and an irregularly shaped nodule in the right apex. Wedge resection of these
      lesions was performed under video-assisted thoracoscopic surgery. Pathological
      examination revealed not only aspergilloma, but also an LCNEC 11 x 7 mm in size,
      which was located close to the aspergilloma. Microscopically, nests of tumor
      cells were distributed peribronchially. Right upper lobectomy and mediastinal
      lymph node dissection was performed, and the pathological stage was IIIA
      (T1N2M0). The patient received four cycles of adjuvant chemotherapy with
      carboplatin and paclitaxel. No recurrence has been observed since surgery. This
      is the first report describing co-existence of pulmonary aspergilloma and LCNEC.

PMID- 17554985
TI  - [A case of primary Sjogren's syndrome complicated with lung adenocarcinoma].
AB  - A 69-year-old woman presented with headache. Her chest radiograph and computed
      tomographic scans showed a mass shadow causing superior vena cava syndrome.
      Bronchofiberscopic examination was nonproductive. The serum value of
      carcinoembryonic antigen was highly elevated, so we made a presumed diagnosis of
      primary non-small lung cancer. She also complained of dry eyes and mouth. The
      elevated values of serum antibodies against SS-A and SS-B and further
      examinations resulted in a definitive diagnosis of primary Sjogren's syndrome.
      Chemotherapy was not effective and she died 14 months later. Autopsy revealed
      that the mass shadow was a primary lung adenocarcinoma. At the age of 66 she
      suffered a refractory pneumothorax and her pulmonary cysts or bullae were
      surgically resected. Those lesions had bullae, emphysema, and alveolar septae
      thickened by infiltration of lymphoplasmacytic cells. Because she had complained
      of xerostomia for the last few decades, we associated the cysts with Sjogren's
      syndrome. Thoracic CT scans at that time showed a nodule next to a cystic lesion.
      We raise a possibility that lung cancer might derive from cystic lesions
      associated with Sjogren's syndrome.

PMID- 17554986
TI  - [A case of legionella pneumonia associated with acute respiratory distress
      syndrome (ARDS) and acute renal failure treated with methylprednisolone and
      sivelestat].
AB  - A 48-year-old man with diabetes mellitus and alcholic chronic pancreatitis was
      admitted to our hospital with fever and dyspnea. Chest x-ray film showed
      infiltration of the right upper lung field and blood exam demonstrated marked
      increase in CPK and renal dysfunction. Intravenous ceftriaxone sodium was
      started, but the next day, we started intravenous ciprofloxacin because the urine
      sample was positive for the Legionella antigen. Hemodialysis was started for
      acute renal failure due to rhabdomyolysis, and mechanical ventilation was
      introduced due to worsening of acute respiratory failure. Despite these
      treatments, bilateral infiltration on chest x-ray worsened, resulting in acute
      respiratory distress syndrome (ARDS). After administration of intravenous pulse
      methylpredonisolone and sivelestat (neutrophil elastase inhibitor), the patient
      was successfully weaned from mechanical ventilation. He was also removed from
      hemodialysis, and discharged from hospital with a good performance status 28 days
      later. The outcome in this case suggested that treatment with pulse steroid and
      sivelestat sodium in addition to antibiotics may be effective for Legionella
      pneumonia complicated by ARDS and acute renal failure.

PMID- 17554987
TI  - [A case of psittacosis with wandering infiltrates developing to acute respiratory
      distress syndrome].
AB  - A 52-year-old woman visited a local hospital with a high fever, non-productive
      cough and general fatigue. Her chest X-ray showed infiltrate in the right middle
      lung field. Computed tomography scans revealed ground-glass opacity and
      surrounding ring-shaped air-space consolidation, the "reversed halo sign".
      Cefpirom was administered, but her symptoms persisted and the infiltrate migrated
      to the left upper lobe. As cryptogenic organizing pneumonia was suspected, she
      was then treated with intravenously pulsed methylprednisolone followed by
      prednisolone. Despite these therapies, acute respiratory failure occurred and she
      was therefore transferred to our hospital. On admission, severe hypoxemia and
      diffuse bilateral infiltrates on chest images suggested acute respiratory
      distress syndrome. As we obtained information that a parakeet had recently died
      at her home, minocycline was administered, resulting in prompt improvement of the
      symptoms, respiratory insufficiency and pulmonary infiltrates. Finally, elevated
      antibody titers against Chlamydophila psittasi confirmed a diagnosis of
      Psittacosis. Sequential chest computed tomography scans in this case indicate
      that absorption of marginal air-space consolidation with extended central ground
      glass attenuation in concordance with a new infiltrate on another lung field
      appeared to create wandering infiltrate. Wandering infiltrate on chest X-ray in
      psittacosis may be a sign of disease progression.

PMID- 17554988
TI  - [FDG-PET findings of nodular pulmonary amyloidosis with a long-term observation].
AB  - A 60-year-old woman was referred to our hospital because of an abnormal chest
      radiograph in May, 2000. She was found to have rheumatoid arthritis in March,
      1998, and pharmacologic therapy with anti-rheumatic drug was started. The chest
      CT scan revealed bilateral multiple lung nodular lesions of various sizes up to
      30 mm. F-18 fluorodeoxyglucose positron emission tomography (FDG-PET)
      demonstrated a lesion with intense FDG activity in the right lung with a
      standardized uptake value (SUV) of 10.1. Fiberoptic bronchoscopy revealed no
      endobronchial lesions. Video-assisted thoracoscopic surgery was done to ascertain
      the pathological diagnosis. Histological examination showed that the pulmonary
      nodules were composed of amyloid A (AA) protein. Secondary Sjogren syndrome was
      subsequently diagnosed. A diagnosis of localized nodular pulmonary amyloidosis
      with AA type amyloid protein was made, and therapy with anti-rheumatic drugs was
      continued. After six years of therapy, the size of pulmonary amyloidoma was
      reduced, and the accumulation of FDG returned to normal. We reported this
      interesting case in which FDG-PET apparently reflected the disease activity of
      pulmonary amyloidosis.

PMID- 17554989
TI  - [Perforation of the small intestine caused by metastasis from primary lung
      cancer: report of two cases and the discussion of 48 cases published in the
      Japanese literature].
AB  - Case 1 was a 62-year-old man who had performance status (PS) of 1 and stage IIIB
      adenocarcinoma of the lung. Because he showed progressive disease after induction
      chemoradiotherapy, he started to receive best supportive care alone. Three months
      after initial diagnosis, he complained of abdominal pain. As a result of computed
      tomography of the abdomen. He was diagnosed with abdominal pain probably caused
      by ileal perforation. An operation was undertaken and the surgical findings
      showed perforation by small intestine metastasis from lung adenocarcinoma. After
      the operation, he survived more than ten months. Case 2 was a 54-year-old man who
      had a PS of 3 and stage IV large cell carcinoma. After chemotherapy and
      sequential cranial radiotherapy, he developed anemia of unknown cause. He also
      complained of an abdominal pain during hospitalization and digestive tract
      perforation was diagnosed by a CT scan of the abdomen. He underwent surgery and
      the surgical findings showed a metastasis of large cell carcinoma in the small
      intestine. He died in a hospice two months after the operation. In the Japanese
      literature from 1983 to 2006. 48 operated cases with perforation caused by small
      intestine metastasis of lung cancer have been reported in full-length papers.
      Although the postoperative median survival time was 48 days, only one surgery
      related death occurred. Patients who had a history of prior cancer treatment
      before surgery tended to achieve more prolonged survival compared to those who
      had not cancer treatment, probably due to poor PS. The preoperative PS may be one
      important prognostic factor in these patients.

PMID- 17554990
TI  - [A case of pulmonary Mycobacterium gordonae infection progressed for no therapy].
AB  - A 68-year-old woman, who had been healthy until this event, presented with a
      complaint of productive cough since 2000. She went to a neighboring hospital
      because of bloody sputum in October 2001. Although chest radiograph showed
      abnormal findings then, she received only an expectorant and cough remedy. She
      consulted us complaining of dyspnea on exertion in April 2005. Chest radiograph
      revealed cavity formation, bronchiectasis and a nodular shadow, and her condition
      had deteriorated. Microbiologically, acid-fast bacilli were detected three times
      in the culture of sputum, and Mycobacterium gordonae was identified by the
      biochemical method. However, this Mycobacterium gordonae could not be identified
      by the DNA-DNA hybridization method. Our case also probably was considered to be
      a primary type pulmonary nontuberculous infection because of her clinical course.
      In addition, we recognized that pulmonary M. gordonae infection also worsens
      without the therapy.

PMID- 17554992
TI  - A middle lobe tractotomy of the lung for a stab injury: report of a survival
      case.
AB  - We report the case of a patient who survived after a pulmonary tractotomy. A 54
      year-old man was stabbed in the back with a knife and was admitted to our
      emergency department. Imaging findings showed that there was hemopneumothorax of
      the right lung. After inserting a chest tube, a massive air leakage from the
      chest drain continued, and a serial chest roentgenogram showed progressive lung
      collapse. The patient therefore underwent an emergency thoracotomy. It was found
      that the wound penetrated through a middle lobe to the surface of an upper lobe
      of the right lung. A right middle lobe tractotomy was performed, and the
      patient's postoperative course was uneventful. Selected patients can be rescued
      without resection of a massive amount of lung tissue.

PMID- 17554991
TI  - Circulating tumor cells in peripheral blood caused by surgical manipulation of
      non-small-cell lung cancer: pilot study using an immunocytology method.
AB  - OBJECTIVE: Reverse transcriptase-polymerase chain reaction assay results have
      indicated that tumor cells sometimes appear during surgery for primary non-small
      cell lung cancer. In this study, we attempted to determine whether cancer cells
      can be detected during and after surgery using an immunocytology method. METHODS:
      Nine patients undergoing a lobectomy for non-small-cell lung cancer were studied.
      The presence of circulating tumor cells was determined by the detection of
      magnified EpCAM antibodies. The criteria used to identify circulating tumor cells
      were a round-to-oval morphology with a visible nucleus (4'-6'-diamidino-2
      phenylindole (DAPI)-positive), which were positive for cytokeratin and negative
      for CD45. RESULTS: One patient showed evidence of circulating tumor cells at
      thoracotomy, and 3 patients did so after surgery. Ten days after the operation,
      the circulating tumor cells had disappeared in all these cases. The median follow
      up period was 14 months, and there was no cancer recurrence in any of the
      patients. CONCLUSION: Using this technique, tumor cells were detected in the
      peripheral blood of patients before and after lobectomy procedures. It could be
      argued that this method can provide useful information about patients undergoing
      lung cancer treatment.

PMID- 17554993
TI  - Surgical repair of coronary sinus orifice atresia with persistent left superior
      vena cava in heterotaxia.
AB  - A 6-month-old boy was diagnosed with coronary sinus orifice atresia, double
      outlet right ventricle, complete atrioventricular septal defect, pulmonary
      stenosis, and moderate common atrioventricular valve regurgitation associated
      with heterotaxy syndrome. Cardiac venous flow drained through a persistent left
      superior vena cava. We decided to perform coronary sinus orifice unroofing
      through the right atrium under a guide using a bougie. The persistent left
      superior vena cava was divided. Bidirectional Glenn anastomosis and edge-to-edge
      common atrioventricular valve repair were concomitantly performed. After a 1-year
      follow-up period, the patient is alive and well without any ischemic event.

PMID- 17554994
TI  - Five cases of blunt traumatic cardiac rupture: success and failure in surgical
      management.
AB  - We report five cases of blunt cardiac rupture seen in our hospital during the
      last 6 years. All these patients sustained blunt chest trauma due to motor
      vehicle or motorcycle accidents, and all had vital signs on arrival at the
      emergency department. We suspected cardiovascular injuries from the findings of
      echocardiography and CT scans, and all five cases were operated on 2-6 h after
      injury. Four had a median sternotomy, and one had a lateral thoracotomy. During
      the operations, we found that two patients had pericardium injuries and all five
      patients had right chamber injuries, which included multiple, ventricle, and
      large venous injuries in three patients. The tears were repaired using simple
      suture or ligation techniques for all patients, with cardiopulmonary bypass in
      three patients. One patient died during the operation, and four patients
      survived, therefore the survival rate was 80%. We believe that patients with
      cardiac rupture who are alive when they reach hospital can often be saved by
      prompt diagnosis and immediate, adequate surgical repairs.

PMID- 17554995
TI  - Transient occlusion procedure with a catheter for peripheral pulmonary artery
      damage caused by percutaneous drainage for lung abscess.
AB  - The patient was a 78-year-old man who had liver and lung abscesses. Percutaneous
      drainage was performed for the lung abscess. While the drainage was successful
      for both abscesses, a drainage tube injured the peripheral pulmonary artery,
      causing hemorrhage and hemosputum. An occlusion technique for the pulmonary basal
      artery using a wedged barman catheter stopped the bleeding, resulting in a
      successful outcome.

PMID- 17554996
TI  - Two cases of colonic necrosis following aortoiliac surgery due to coronary
      induced cardiogenic shock.
AB  - We report two cases of abdominal aortic aneurysm in which the patent inferior
      mesenteric arteries were ligated. The patient in Case 1, with occlusion of the
      right coronary artery, developed sudden bradycardia during surgery, resulting in
      cardiac arrest. The patient was successfully resuscitated and the operation was
      completed. In Case 2, acute thrombotic obstruction occurred postoperatively in
      the stent previously implanted in the left anterior descending coronary artery.
      Although the thrombus was removed by aspiration, hypotension was sustained. In
      both cases, colonic necrosis extending from the descending colon to the rectum
      developed following cardiogenic shock. The affected portion of the colon was
      resected and a colostomy was constructed. The incidence of coronary arterial
      disease is high in patients with abdominal aortic aneurysm. The occurrence of
      cardiac complications is not rare, and may result in catastrophic consequences.
      Therefore the inferior mesenteric artery should be reimplanted, especially in
      patients with concomitant heart disease.

PMID- 17554997
TI  - Type B aortic dissection associated with Salmonella infection.
AB  - A 59-year-old man with a long history of hypertension and diabetes was admitted
      to our hospital with acute type B aortic dissection 14 days after the sudden
      onset of back pain. The dissecting descending thoracic aorta was enlarged to 5.2
      cm in diameter, and laboratory tests showed an elevated white blood cell count
      (15530/mm3) and an increased C-reactive protein level (19.2 mg/dl). Computed
      tomography performed 2 days after admission revealed rapid growth of the aortic
      dissection. Blood cultures obtained upon admission were positive for Salmonella.
      Impending rupture of the aortic dissection complicated by Salmonella infection
      was strongly suspected, and the patient underwent emergency surgery consisting of
      debridement and prosthetic graft placement covered by an omental flap. In this
      case, it is believed that insidious Salmonella aortitis caused acute type B
      aortic dissection.

PMID- 17554998
TI  - Large-cell carcinoma of the lung with a remarkable preoperative elevation of
      serum carcinoembryonic antigen level.
AB  - Carcinoembryonic antigen, a serum tumor marker, is useful for diagnosing cancer
      and for following the response to therapy in cancer cases. Serum carcinoembryonic
      antigen levels are also important as a predictive tool in evaluating prognosis. A
      56-year-old man presented with an abnormal shadow on a chest X-ray. His
      preoperative serum carcinoembryonic antigen was at an elevated level of 1274.0
      ng/ml. Chest computed tomography revealed a tumor in the posterior segment of the
      right lung and a swollen right interlobar lymph node. Right lung pneumonectomy
      and node dissection were performed. A histological diagnosis determined that the
      tumor was a large-cell carcinoma at clinical stage IIA. Immunohistochemical
      analysis detected the production of carcinoembryonic antigen by the tumor cells.
      Following surgery, the patient's carcinoembryonic antigen levels were maintained
      within the normal range. This is a rare case of lung cancer with no evidence of
      recurrence and metastasis for 8 years despite markedly elevated preoperative
      carcinoembryonic antigen levels.

PMID- 17554999
TI  - Sliding tricuspid valvuloplasty for severe tricuspid regurgitation after
      corrective surgery of a ventricular septal defect.
AB  - We encountered a case of massive tricuspid regurgitation after corrective surgery
      for a ventricular septal defect. Fixation of the septal leaflet to the
      ventricular septum at the point where it was closed with a pericardial patch and
      marked annular dilatation were the lesions contributing to the severe tricuspid
      regurgitation. The posterior leaflet of the tricuspid valve was excised from the
      tricuspid annulus, slid to the adhering septal leaflet, and then reattached to a
      safe area of the septal leaflet to prevent conduction disturbance. The sliding
      repair was supported by annuloplasty with a Carpentier-Edwards ring, and a
      concomitant right-sided Maze procedure was conducted for atrial flutter.

PMID- 17555000
TI  - Selective lobar bronchial blockade using a double-lumen endotracheal tube and
      bronchial blocker.
AB  - We report our experience of a selective lobar bronchial blockade (SLBB) technique
      with a bronchial blocker (BB) which was employed successfully with a routine
      double-lumen endotracheal tube (DLT) in three patients. For the first case, we
      selectively blocked the infected left lower lobe in a surgical patient with a
      lung abscess in a DLT setting. For the second case, we applied this method to
      block the right middle and lower lobes in order to assess air leakage from the
      upper lobe during video-assisted thoracic surgery (VATS). For the third case,
      selective continuous positive airway pressure (CPAP) to the blocked lobes on the
      operative side resulted in oxygenation improvement with one-lung ventilation
      (OLV) in a DLT. This novel technique provides benefits during general thoracic
      surgery by preventing contamination, providing a better operative field, and
      improving oxygenation with lobar CPAP.

PMID- 17555001
TI  - [The importance of medical-psychiatric rehabilitation].

PMID- 17555002
TI  - [Assessment of sexual deviance by forensic psychiatrists].
AB  - The article reviews the legal changes in dealing with sexual offenders in Germany
      during the last ten years. The developments described are in many respects
      comparable to other countries of Northern and Western Europe and to Austria. The
      laws, which regulate the penal aspects for sexual deviance, have been drastically
      tightened up. Publicist, political and public pressure against perpetrators and
      their advocates has massively grown; the number of committals in special
      institutions has dramatically increased. On the other hand the handling of these
      individuals by forensic psychiatrists has become much more professional.
      Standards for the assessment of culpability have been established, the treatment
      facilities have been largely extended, instruments for risk assessment and the
      prediction of recidivism have been developed and validated for German speaking
      countries. With respect to the political consideration to coercive treatment and
      for tightened and prolonged security measures for all sexual perpetrators
      professionals have to emphasize that sexual deviant individuals have to be
      differentiated, not only regarding their crimes and their personality but also
      regarding their potential to profit from treatment and their probability for
      recidivism

PMID- 17555003
TI  - [Drug-therapy with sexual offenders].
AB  - Sexual offenders are a heterogeneous group of offenders with different
      personality structures and different patterns of crime. As a consequence,
      difficulties arise with the definition of sexually deviant or offending
      behaviour, which depends on period of time and culture. After presenting the
      actual definition of sexual offences, their frequency is shown by means of German
      epidemiological data. The problem of the assumed relationship between paraphilia
      and sexual offending behaviour is called into question. After the description of
      the central neurobiological and endocrinological mechanisms, the established
      pharmacological treatment strategies (Selective Serotonine Reuptake Inhibitors,
      Antiadrogenes, LHRH (Luteotropic Hormone Releasing Hormone)-Agonists) are
      presented. Finally, the step-wise algorithm for the therapy of sexual according
      to Bradford is presented.

PMID- 17555004
TI  - [The economics of mental health and health care- a blind spot?].
AB  - Mental disorders are associated with an immense burden of disease for patients,
      their social environment and for society as a whole. Neuropsychiatric diseases
      have been estimated to account for 27% of disability adjusted life years (DALYs)
      in the Euro-A region and have thus more impact on the global burden of disease
      than cardiovascular diseases or neoplasms. In the population younger than 30
      years even 65% of years lost due to disability are due to neuropsychiatric
      disorders. Moreover, the economic consequences of mental disorders pose a
      significant challenge on health care systems. For example, it has been estimated
      that 10% of direct health care costs in Germany were caused by mental and
      behavioural disorders in 2002. With limited available resources, it is becoming
      increasingly important to allocate health care budgets efficiently. It is
      therefore surprising that mental disorders as compared to other diseases are
      considerably underrepresented in the health economic evaluation of health care
      interventions. Health economic research has concentrated on the pharmacoeconomic
      assessment of new drugs so far while other interventions and alternative ways of
      care delivery, e.g., specialized day care, have rarely been subject to health
      economic evaluation and are thus systematically disadvantaged. Causes underlying
      the reservation towards mental disorders in health economics are being discussed
      and future perspectives are outlined.

PMID- 17555005
TI  - [Informal care of people with mental disorders: does the Austrian long-term care
      system provide adequate support?].
AB  - OBJECTIVE: The Austrian long-term care system covers all types of long-term
      chronic diseases and handicaps and is based on a payment for care scheme. The
      benefit is directed to care recipients, who are - in the outpatient sector -
      largely free in how to use it. Herewith, the payment for care scheme also has a
      significant impact on the provision of informal care. The paper studies this
      impact for the particular case of informal care provided for mentally ill people.
      METHODS: The analysis is based on a questionnaire survey of persons that are
      providing informal care to mentally ill people in Austria. The data is confronted
      with results from other studies on informal care provision in Austria. RESULTS:
      The study shows specific characteristics of informal long-term care for people
      with mental illness which is associated with specific burdens for the informal
      carers. Carers and care recipients benefit only to a moderate extent from public
      long-term care benefits and bear comparably high material and social costs.
      CONCLUSIONS: The cash-oriented long-term care system in Austria offers only
      limited support for the particular case of informal care provided for mentally
      ill people. The long-term care system needs to be tailored to the special needs
      of both carer and care recipient in order to achieve the stated aim of self
      determination and freedom of choice.

PMID- 17555006
TI  - [Early detection of psychotic disorders].
AB  - Over the last decade there has been considerable interest in early intervention
      in schizophrenia and other psychotic disorders, driven by observations that early
      intervention might favorably alter the course of illness. New clinical and
      research programs have been established around the globe aiming to reduce
      treatment delays in psychosis and, more recently, to identify and possibly treat
      individuals in the pre-psychotic phase who are at imminent risk of developing
      psychosis. Since May 2004, a service for individuals at high risk (HR) for
      psychosis has been established at Vienna General Hospital. Individuals are
      offered comprehensive assessment and treatment which includes participation in a
      RCT investigating the effects of Omega-3 fatty acids versus placebo in addition
      to standard care. The aim of this article is to describe (1) classification of
      psychotic symptoms in incipient psychosis and (2) findings of the screening
      process as well as baseline characteristics in individuals with and without
      transition to psychosis. INCLUSION CRITERIA: 1. Age 13 to 24 years 2. High Risk
      (HR) as classified by Yung et al. (1998) HR criteria: one or more of following
      characteristics occurred within the last 12 months: 1. Frank psychotic symptoms <
      1 week 2. Attenuated psychotic symptoms > 1 week, several times per week 3. Drop
      in GAF of > 30% (>1 months) plus family history of psychosis or individual has
      schizotypal personality disorder Other psychiatric measures: SCID for DSM-IV,
      PANSS, MADRS, and the UKU side effect rating scale. Between May 2004 and June
      2005, 140 individuals were referred to our service for suspected psychosis. 69
      individuals (49,3%) met HR criteria, 21 (15%) were detected with first-episode
      psychosis at initial presentation; 50 (35,7%) individuals did not meet criteria
      for HR or DSM-IV psychotic disorder. 42 (60,9%) of 69 individuals with HR agreed
      to participate in the proposed EPA/DHA treatment trial. Co-morbidity of axis-I
      disorders was high in the HR group: 54,3% affective disorders, 40%
      anxiety/obsessive-compulsive disorders, 14,3 substance related disorders, 11,4%
      eating disorders and 2,9% somatoform disorders. To date 6 (14,3%) individuals
      have made a transition to psychotic disorder. These subjects scored significantly
      higher at the negative and at the general psychopathology scale ofPANSS and at
      the MADRS at time of randomization. Early detection and intervention in psychotic
      disorders seems to be a feasible goal which can be achieved in an outpatient
      setting. Individuals with HR can be detected and already show a substantial loss
      of functioning. In the process of screening for individuals with HR a high number
      of undiscovered cases of psychosis can be found. Given their high prevalence,
      treatment of comorbid axis-I conditions should be carefully addressed in HR and
      studied in relation to the risk of progression to psychosis. In contrast to
      antipsychotics, Omega-3 fatty acids have a high acceptance among youth and
      parents. At this stage the role of Omega-3 fatty acids remains unclear because
      the trial is not finished yet.

PMID- 17555007
TI  - [Recovery in mental health].
AB  - Recovery from severe mental illness has become an increasingly relevant concept
      in the mental health field. Today, recovery orientation has already been
      introduced into mental health service provision in numerous countries. However,
      there is still confusion about both the theoretical concept as well as its
      practical implications. In this paper, we present a narrative literature review,
      illustrating the concept of recovery from different perspectives, outlining the
      related concept of resilience, and highlighting some practical issues of recovery
      orientation in mental health service provision.

PMID- 17555008
TI  - [The "European Alliance Against Depression". An European network targeting at
      effective care in community-based services for persons suffering from depressive
      disorders].
AB  - Action programmes fostering partnerships and bringing together regional and
      national authorities to promote the care of depressed patients are urgently
      needed. In 2001 the "Nuremberg Alliance Against Depression" was initiated as a
      community-based model project within the large-scaled "German Research Network on
      Depression and Suicidality" (Kompetenznetz "Depression, Suizidalitdat") which was
      funded by the German Federal Ministry on Education and Research. The "Nuremberg
      Alliance Against Depression" was a 4-level action programme, conducted in the
      city of Nuremberg (500,000 inhabitants) and addressing 4 parallel intervention
      levels. The project has been evaluated both with respect to a 1-year baseline and
      a control region (city of Wurzburg). With confirmatory statistics a significant
      reduction of suicidal behaviour by more than 20% was observed. Based on these
      positive results the "German Alliance Against Depression" was founded in 2002,
      which coordinates the implementation of similar intervention programmes all over
      Germany and within German-speaking regions of Switzerland, Austria and Italy. In
      2004 18 international partners representing 16 different countries, a WHO work
      group and a professional IT-partner established the "European Alliance Against
      Depression". Supported by the European Commission an international network has
      been built up. In 2006, two further partners joined the EAAD network. The
      successful basic principle of an action-oriented programme that intervenes on
      various levels and utilises knowledge and expertise of an international network
      of experts in combination with a number of established regional activities forms
      the core principle of EAAD. During the next months the regional campaigns and
      already existing networks will be expanded to other regions and--where possible-
      to national level. Future EAAD intervention activities and regional campaigns
      will aim at special target groups to a higher degree, especially focusing on
      prevention of depressive disorders and suicidal behaviour among children and
      adolescents. Overall, EAAD may serve as an example of how European community
      based "best practice" models for improving the care of depressed patients and
      suicidal persons can be implemented using a bottom-up approach (starting from a
      regional model project to a national expansion of activities and policy relevant
      recommendations). The European Commission presented the EAAD project as one of
      the most promising strategies in the area of mental health at the WHO European
      Ministerial Conference on Mental Health in Helsinki and listed EAAD in its Green
      Paper "Improving the mental health of the population: Towards a strategy on
      mental health for the European Union".

PMID- 17555009
TI  - [One-night psychotic episode during topiramate treatment in connection with an
      acute febrile infection].
AB  - Topiramate is an anticonvulsant which has been used more and more in recent years
      in psychiatry as well. The undesirable effects that have been observed remain
      relatively mild under conditions of slow titration. Psychotic symptoms have been
      described in connection with the use of topiramate in individual cases, however.
      It is not known which concomitant circumstances favour the appearance of this
      side-effect, though. This is a report about a psychotic attack that happened for
      the first time and lasted for one night in a borderline patient who was treated
      with topiramate 250 mg/day shortly after the start of a febrile infection. After
      the infection had gone, topiramate was given again and titrated to 300 mg/day. No
      further psychotic symptoms were observed.

PMID- 17555010
TI  - UIC is prepared for the future.

PMID- 17555011
TI  - Fast food TV commercial reinforces dental phobia, irks columnist.

PMID- 17555012
TI  - Why evidence-based dentistry matters.

PMID- 17555013
TI  - Role reversal. Dentists are often the first responders in healthcare.

PMID- 17555014
TI  - Starting over. Survivors of torture find Chicago is sweet home.

PMID- 17555015
TI  - You get the behavior you expect.

PMID- 17555016
TI  - Is 'networking' a dirty word?

PMID- 17555017
TI  - Serendipity can be a strange thing.

PMID- 17555018
TI  - Recognize the warning signs.

PMID- 17555019
TI  - Great moments dental floss.

PMID- 17555020
TI  - You don't want the pony on top if you're at the bottom of a two-tier system.

PMID- 17555021
TI  - It's YOUR association after all.

PMID- 17555022
TI  - Enteral [corrected] conscious sedation and emergency procedures for Texas dental
      practitioners.

PMID- 17555023
TI  - The CSI effect: redefining dentistry's role in forensic sciences.

PMID- 17555024
TI  - The root of ethics.

PMID- 17555025
TI  - Oral and maxillofacial pathology case of the month. Foreign body gingivitis.

PMID- 17555026
TI  - Suicide and Asperger's syndrome.

PMID- 17555027
TI  - Outcome of suicidal ideation and behavior in a young, help-seeking population
      over a 2-year period.
AB  - Suicidal behavior is associated with negative outcomes, including completed
      suicide. This study examined the prevalence of suicidal behavior in a sample of
      referrals to a youth psychiatric service and investigated the stability of
      suicidality over 2 years. Of the 140 people (mean age 17.8) who were referred to
      a youth psychiatric service, 82 who were accepted for treatment (RA group) and 58
      who were not accepted (RNA group) were assessed; 57% reported considering suicide
      and 39% reported attempting suicide in the 12 months prior to referral.
      Participants who reported suicidal ideation were significantly more likely than
      nonsuicidal participants to have multiple Axis I diagnoses and lower levels of
      functioning. At the 2-year follow-up there was a significant reduction in
      suicidality in the RA group, but not in the RNA group. In conclusion, suicidality
      is prevalent among young people referred to psychiatric services. Even brief
      contact with services results in a reduction in suicidality over 2 years.

PMID- 17555028
TI  - Suicide in Bahrain in the last decade.
AB  - A combination of social, legal, and religious factors make reporting of suicide
      difficult in Bahrain, an Islamic country. Limited available data indicates a very
      low incidence rate of 3 per 100,000. The objective of the present study was to
      describe the pattern of suicide in Bahrain during a 10-year period. The
      registered suicide cases (N = 304) at the Ministry of Interior for the 10-year
      period from 1995 to 2004 were reviewed and analyzed. The mean suicide rate was
      0.6 per 100,000 for the Bahraini nationals and 12.6 per 100,000 for the non
      Bahrainis with and 17.7 per 100,000 for the Indian migrants. Men were six times
      more likely than women to commit suicide. The majority of the subjects were under
      35 years of age with financial domestic problems being the most common reason
      reported in the record and hanging the mostly commonly used mode of suicide
      (92.8%). The suicide rate for the Bahraini population remains low compared to
      other countries. The higher rate of suicide among Indians merits further
      investigation. Moreover, more research is needed on the epidemiology of suicide
      risk factors in ethnic groups for further prevention and intervention.

PMID- 17555029
TI  - Addressing suicidal ideations through the realization of meaningful personal
      goals.
AB  - A personal goal intervention program was offered to early retirees aged 50 to 65
      years with the objective of increasing their subjective well-being. The program
      was aimed at helping the participants set, plan, pursue, and realize their
      personal goals. A subsample of 21 participants with suicidal ideas was identified
      from a larger sample (N = 354) of retirees living in the community who took part
      in the study to evaluate the program. The experimental (n = 10) and control (n =
      11) groups were compared on their answers to 16 goal and psychological well-being
      questionnaires. By the end of the program, the experimental group had improved
      significantly more than the control group on hope, goal realization process,
      serenity, flexibility, and positive attitude toward retirement. The levels of
      depression and psychological distress significantly decreased. These gains were
      maintained 6 months later. The positive results obtained from this study could
      lead to an innovative way to help people with suicidal ideations.

PMID- 17555030
TI  - The lived experience of adults bereaved by suicide: a phenomenological study.
AB  - In recent years, a plethora of research studies have attempted to delineate the
      grief experiences associated with suicide from those of other sudden traumatic
      deaths. The emerging consensus suggests that bereavement through suicide is more
      similar than different to other bereavements, but is characterized by the
      reactions of shame, stigma, and self-blame. The causal nature of these reactions
      has yet to be fully understood. This study reports on the lived experiences of
      eight adults bereaved by suicides, which were obtained through in-depth
      interviews. Data were analyzed using interpretative phenomenological analysis.
      Four main themes dominated the relatives' grief experiences. First, the early
      months were checkered by attempts to "control the impact of the death." The
      second theme was the overwhelming need to "make sense of the death" and this was
      coupled with a third theme, a marked "social uneasiness." Finally, participants
      had an eventual realization of a sense of "purposefulness" in their lives
      following the suicide death. Overall, the findings suggest that suicide
      bereavement is molded and shaped by the bereaved individual's life experiences
      with the deceased and their perceptions following social interactions after the
      event. The findings from this study suggest that "meaning making" may be an
      important variable in furthering our understanding of the nuances in suicide
      bereavement.

PMID- 17555031
TI  - Suicide prevention training outside the mental health service system: evaluation
      of a state-wide program in Australia for rehabilitation and disability staff in
      the field of traumatic brain injury.
AB  - The training needs of staff working in mainstream (i.e., noncrisis) health
      settings with client groups that have moderate levels of suicide risk have not
      been extensively addressed. An initiative to train rehabilitation and disability
      staff working in the field of traumatic brain injury (TBI) is described. A
      program was adapted from a generic state health department training program, and
      disseminated by means of established training networks within the brain injury
      field. Program efficacy was evaluated as the training was provided across the
      state of Victoria in a series of 1-day workshops. Participants (n = 86) completed
      two evaluation measures designed for this purpose (objective knowledge test, self
      rating of knowledge and skills) on three occasions (pre- and postworkshop, 6
      month follow-up). Compared to a control group of rehabilitation and disability
      workers who did not receive the training (n = 27), the workshop participants made
      significant gains in objective knowledge and reported skills, and maintained
      these gains at the 6-month follow-up. The Suicide Interview Response Inventory-2
      (Neimeyer & Pfeiffer, 1994) was administered to a subgroup of participants as a
      validating measure, and correlated significantly with scores from the objective
      knowledge test. This process may provide a template for developing more fine
      grained suicide prevention strategies among other health-related at-risk groups.

PMID- 17555032
TI  - Two further comments on Durkheim's Le Suicide.
AB  - It appears that the publications of Goldney and Schioldann (2000, 2001a,b, 2002)
      touched a chord, namely, the quality of the basic literature of contemporary
      suicidology and the usage of certain words and concepts. This paper adds two
      comments to this discussion. The first comment focuses on the usage of
      "altruistic," "egoistic," and "anomic" suicide. The second is a comment on the
      reception of Le Suicide.

PMID- 17555033
TI  - Body mass and suicide risk.
AB  - Body mass has been neglected as a possible predictor of suicidal behavior. The
      present investigation explores the association between body mass index and
      completed suicide. Data are from the National Mortality Followback Survey and
      refer to 373 suicides, and 518 deaths from motor vehicle accidents as controls.
      The results of a logistic regression analysis indicated that, for females, the
      greater the BMI the greater the suicide risk. However, this relationship did not
      hold up under controls for race and other covariates of BMI. For males, the BMI
      was not significantly related to suicide risk either at the bivariate or
      multivariate levels of analysis. The best predictors of suicide were living alone
      for females, and alcohol abuse for males.

PMID- 17555034
TI  - On the Werther effect: a reply to Krysinska and Lester.

PMID- 17555035
TI  - [Effect of isoflurane inhalation anesthesia on postoperative pain due to
      castration of piglets].
AB  - Since April 2006 piglets in Germany can only be castrated without anesthesia in
      the first 7 days of life. However, a castration is a painful experience even for
      an animal of this young age. Whether the castration under isoflurane-anesthesia
      is a reasonable alternative to castration without anesthesia was tested in the
      following investigation at 206 4 to 6 day old piglets. The serum-cortisol
      concentration was chosen as the parameter for the pain caused by castration. A
      part of the animals was castrated without anesthesia (group II, n = 42) or with
      anesthesia (group IV, n = 41). Additionally Meloxicam, a non-steroidal anti
      inflammatory drug, was applicated to piglets castrated with anesthesia (group V,
      n = 41). For control another part of the animals were only handled without (group
      I, n = 41) or with anesthesia (group III, n = 41), but they were not castrated.
      Cortisol-concentration prior to castration was compared to the concentration 0.5,
      1,4 and 24 hours after castration. In addition cortisol was compared between
      groups at all points of time. Cortisol did rise significantly in castrated
      animals with animals with or without anesthesia than in animals of the non
      castrated control groups. Cortisol after castration was significantly lower in
      piglets with an application of Meloxicam prior to castration. The pain caused by
      castration is an explanation for the differences in cortisol-concentration
      between castrated and not-castrated animals. Regarding those results, we assume
      that castration with isoflurane-anesthesia does not fulfil the demand for
      reducing pain after castration compared to castrating piglets without anesthesia.

PMID- 17555036
TI  - [Successful rehabilitation and release with a subsequent brood of a one-eyed
      eagle owl (Bubo bubo)].
AB  - The rehabilitation and release of injured or ill raptors and owls is widespread.
      The overall aim of this intervention is the successful reintroduction of the bird
      into the wild population. Though many injuries are treatable, it is thought that
      vision-impaired birds have no change of survival and their release is refused.
      Here we report a case study and give a description of the rehabilitation and
      subsequent release of an injured Eagle Owl (Bubo bubo). The bird was found with
      an injured eye and a paralysed wing in the district of Soest, North Rhine
      Westphalia, Germany. While the paralysis healed, the bird stayed blind in one
      eye. Nevertheless it was released with a radio-transmitter. The female Eagle Owl
      could be followed by radio-telemetry for more than half a year after release, by
      visual and acoustic skills for a full year after release. Although the female was
      only two years old, it paired successful with a partner, and raised a brood with
      three offspring. No differences in the behaviour compared to non-handicapped
      birds could be detected. This one-eyed Eagle Owl demonstrates not only survival,
      but also successful reproduction following reintegration into the wild
      population. However, low intraspecific competition in the area might have
      contributed to the reproductive success of the owl.

PMID- 17555037
TI  - Evaluation of the effectiveness of selected measures against bovine spongiform
      encephalopathy (BSE) in Switzerland by use of the basic reproduction ratio R0.
AB  - The effectiveness of two measures against Bovine Spongiform Encephalopathy (BSE),
      the compulsory processing of animal by products to meat and bone meal (MBM) at
      133 degrees C under 3 bars of pressure for 20 minutes in February 1993 and the
      exclusion of fallen stock, heads with eyes and spinal cord of cattle older than
      30 month from MBM production in April 1996, was evaluated in a process model. The
      transmission of BSE by calculation of the basic reproduction ratio R0 was
      modelled. The results were verified by use of a cohort model, based on observed
      surveillance data. Prior to 1990, before the ban of feeding MBM to ruminants, R0,
      as calculated in the process model, was above 1, coherent with a slowly
      progressing BSE epidemic. Since 1991, values of R0 were low at 0.06. The
      corresponding R0 values derived from the cohort model were higher, the lowest
      value 0.13 calculated for 1996. Given such low R0 values, the epidemic should
      have died out. Additionally, no influence of the two measures was obvious at that
      time given the low level of R0. The discrepancy between the results of the two
      models is evidence for a dependency of the BSE epidemic from an infection source
      not considered in the process model. This infection source is most likely
      importation of feed ingredients and MBM.

PMID- 17555038
TI  - [Detection frequency of haemoplasma infections of the domestic cat in Germany].
AB  - We present epidemiological data on the frequency of infections with haemotrophic
      Mycoplasma spp. (feline haemoplasmas) in domestic cats in Germany. From November
      2004 to October 2006 135 blood samples of anaemic patients and cats without
      clinical symptoms were examined with conventional and real-time PCR methods. In
      15,6 % of the samples DNA of one or more haemoplasma species could be detected.
      8,9 % of the samples (12 cats) were infected with "Candidatus Mycoplasma
      haemominutum, whereas 7,4 % (10 cats) were infected with Mycoplasma haemofelis.
      Out of these, one cat harboured both species. The recently described species
      "Candidatus Mycoplasma turicensis" was found in 2.2 % of all samples (3 cats) and
      was restricted to animals coinfected with M. haemofelis. No correlation could be
      detected between the infection with haemotrophic Mycoplasma spp. and clinical
      signs of anaemia or disease. Infections were significantly correlated with age,
      male gender or coinfections with retroviruses (FIV, FeLV). Our data indicate,
      that chronically infected carriers without clinical symptoms are frequent in the
      investigated cat populations in Germany and that the screening of blood-donors
      for the presence of Mycoplasma spp. infections is advisable before clinical use.

PMID- 17555039
TI  - [Investigation of a possible chain of Streptococcus suis infection in a pig
      breeding community using PCR-based genotyping].
AB  - Streptococcus (S.) suis plays an important role in pig breeding causing invasive
      diseases such as meningitis and polyarthritis. Herd problems with Streptococcus
      suis are common in many pig farms and are frequently characterised by disease
      outbreaks. In this context, it is often important to identify chains of
      infection, e.g. between a farrow-to-wean and a grower farm. In the following case
      report a possible chain of infection among the different farms of a farrow-to
      finish system was investigated. In two grower units herd problems with S. suis
      were present; the mortality was higher than 5 %. It appeared likely, that the
      streptococci causing these problems were transmitted from a single farrow-to-wean
      unit to the two different grower farms. In the respective farms swabs were taken
      from different healthy animals and, in the case of the grower farms, also from
      the infected animals. Genotypic profiling of strains by a multiplex-PCR and AFLP
      typing method revealed that two different S. suis pathotypes were responsible for
      the herd problems. Both pathotypes could not be detected in the farrow-to-wean
      farm.Thus, a chain of infection originating from the farrow-to-wean farm appeared
      unlikely. The multiplex PCR was in this case sufficient to elucidate the
      described problem.

PMID- 17555040
TI  - Adhesion activity of glyceraldehyde-3-phosphate dehydrogenase in a Chinese
      Streptococcus suis type 2 strain.
AB  - A total of 36 streptococcal strains, including seven S. equi ssp.zooepidemicus,
      two S. suis type 1 (SS1), 24 SS2, two SS9, and one SS7, were tested for
      glyceraldehyde-3-phosphate dehydrogenase gene (gapdh). Except from non-virulent
      SS2 strain T1 5, all strains harboured gapdh. The gapdh of Chinese Sichuan SS2
      isolate ZY05719 and Jiangsu SS2 isolate HA9801 were sequenced and then compared
      with published sequences in the GenBank. The comparison revealed a 99.9 % and
      99.8 % similarity of ZY05719 and HA9801, respectively, with the published
      sequence. Adherence assay data demonstrated a significant ((p<0.05)) reduction in
      adhesion of SS2 in HEp-2 cells pre-incubated with purified GAPDH compared to non
      pre-incubated controls, suggesting the GAPDH mediates SS2 bacterial adhesion to
      host cells.

PMID- 17555041
TI  - An evaluation of the effect of repeated doses of oral activated charcoal on the
      depletion of enrofloxacin residual levels in chicken breast muscles.
AB  - The purpose of this study was to determine whether concurrent oral administration
      of activated charcoal has an affect on the depletion of the residual
      concentrations of enrofloxacin (ENRO) in chicken breast muscles. Sixty-four
      broiler chickens were divided into four groups (n = 16 per group), one given a
      daily oral dose of enrofloxacin with feed at a dose of 10 mg/kg for 5 consecutive
      days (control group) and the others given the same dose of enrofloxacin
      simultaneously with activated charcoal at a dose rate of 0.5, 1, and 2 % of daily
      feed for 5 days (treatment groups). At the end of treatment, 2 hens were
      sacrificed at each of the sampling time points (6,12, 18,48, 72,96,120 and 144 h
      after completion of dosing), breast muscles were collected and analyzed.
      Supercritical fluid extraction and high-performance liquid chromatography methods
      were used to determine the enrofloxacin residue levels in chicken breast muscles.
      The limit of quantification (LOQ) 16.5 microg/kg, was lower than the maximum
      residue levels (MRL) fixed by the Commission of the European Union. For all the
      time periods, charcoal treatment did not affect enrofloxacin tissue
      concentrations except at 12 and 48 h post treatment. To our knowledge, no studies
      on the depletion of enrofloxacin in the presence and absence of activated
      charcoal in chicken muscles have been performed. Although our current
      understanding is incomplete, multiple dose activated charcoals may play a role in
      the therapy of overdose. To prove this, further investigation is warranted.

PMID- 17555042
TI  - Single-dose pharmacokinetics of marbofloxacin in Egyptian buffalo (Bubalus
      bubalis L.) steers.
AB  - The objective of this study was to investigate the pharmacokinetics of
      marbofloxacin (MAR) following intravenous (iv) and intramuscular (im)
      administration of a 2.0 mg/kg body weight dosage to five healthy Egyptian buffalo
      steers. A cross-over design was used with a washout period of 2 weeks. Blood
      samples were obtained at 0, 5,10,15, and 20 min and at
      0.5,0.75,1,2,4,6,8,10,12,24,30 and 48 hours after marbofloxacin administration.
      The serum marbofloxacin concentrations were quantitated using a modified agar
      diffusion bioassay method. Marbofloxacin exhibited a relatively high volume of
      distribution at steady-state (Vdss = 1.77 Lkg), which suggests good tissue
      penetration, and a total body clearance (Cltot) of 0.18 L/kgxh,which is
      associated with a long elimination half-life (tl/2beta = 7.52 h). Marbofloxacin
      was rapidly absorbed at a dosage of 2.0 mg/kg after im administration with an
      observed maximum serum concentration (Cmax) value of 2.004 microg/mL obtained at
      a time to peak concentration (tmax) of 0.5 h, and an absolute bioavailability (F
      %) of 86.79 +/- 5.53 %. The protein-binding ranged from 22 to 24.6 % with an
      average of 23.4 %. In conclusion, single iv and im administered doses of
      marbofloxacin were well tolerated by Egyptian buffalo steers. A dosage of 2 mg/kg
      body weight might not be enough to treat infections caused by bacteria with
      minimum inhibitory concentration (MIC) at or above 0.2 microg/mL, based on the
      calculated area under the inhibitory concentration (AUIC).

PMID- 17555043
TI  - Effect on the immune system of germ-free piglets of probiotics potentiated with
      polyunsaturated fatty acids.
AB  - The present study investigated the influence of polyunsaturated fatty acids
      (PUFA) on the immune system of germ-free piglets. Oil with increased content of
      omega-3 PUFA was administered to piglets from the experimental group (EG) for
      four weeks. Piglets from the control group (CG) received identical volumes of
      saline solution. At the age of 21 days both groups of germ-free piglets were
      inoculated perorally with Lactobacillus casei subsp. casei at a dose of 2 ml
      (1x10(8) mli). At the age of 28 days, i.e. after one-week colonisation of germ
      free piglets with Lactobacillus casei subsp. casei, significant differences were
      recorded in phagocytic activity of neutrophils (PANe) and phagocytic activity of
      potentially phagocytizing cells (PA) (P < 0.05). Between EG and CG there have
      been observed no significant differences in absolute numbers of CD4+ and CD8+ T
      lymphocytes and numbers of IgM cells and in additional investigated parameters -
      number of CD2+ T lymphocytes, index of phagocytic activity of neutrophils (IPANe)
      and index of phagocytic activity (IPA). The total number of leukocytes (Le) in EG
      was also higher. Of the parameters determined in blood serum we observed a
      significant increase in concentration of alpha linolenic, eicosapentaenoic and
      docosahexaenoic acids and a parallel decrease in the level of arachidonic acid.

PMID- 17555044
TI  - [Some serum parameters of first lactation cows in relation to their supply of
      macro and trace elements as well as of vitamins].
AB  - At the Institute of Animal Nutrition of the Federal Agricultural Research Centre
      (FAL) in Braunschweig a feeding trial with 30 first lactating cows (German
      Holstein) was realised in 2004 for a complete lactation. All animals received a
      diet based on maize- and grass-silage ad libitum at the rate of 60:40 (DM-base)
      and concentrate depending on their milk yield.The animals were fed with energy
      and protein as recommended (GfE 2001) and were kept in loose housing. After
      calving they were split randomly into two feeding groups with 15 animals each.
      Group 1 was fed a concentrate according to the recommendations of the GfE (2001),
      whereas group 2 was offered the same concentrate with roughly the double amount
      of calcium, magnesium, phosphorus, copper, zinc, beta-carotene and vitamins A and
      E. To study the influence of the different concentrates on the serum
      concentrations of minerals and vitamins, blood, feed and milk samples were
      regularly taken and analysed in the course of lactation. Significantly higher
      blood concentrations were detected for phosphorus, zinc and vitamin E in group 2,
      but therefore a direct influence of the feeding on the blood concentrations was
      detected only for zinc and vitamin E. Over the whole lactation the average milk
      yield of group 1 was 2.6 kg/day higher and the average milk fat content was
      reduced about 0.6 percent points compared to group 2.

PMID- 17555045
TI  - [Analysis of the mode of inheritance for distichiasis in the Elo dog breed using
      complex segregation analyses].
AB  - The inheritance of distichiasis was analyzed in the dog breed Elo using complex
      segregation analyses. The different hypotheses of monogenic, mixed-monogenic
      polygenic and polygenic inheritance as well as a pure environmental model were
      tested. In further analyses the number of examined Elo dogs per ophthalmologist
      and the proportion of genes of Eurasian and Old English Sheepdogs were included
      in the models as covariates. Seven families were randomly collected for the
      analyses. The seven families comprised a total of 296 animals with 218 examined
      and 65 affected dogs. A genetic component was verified for the prevalence of
      distichiasis. Mixed models with a recessive, dominant or arbitrary major gene
      effect and the polygenic model represented likely hypotheses of inheritance. The
      prevalence of distichiasis observed was insufficiently explained by non-genetic
      factors and the breed composition. Therefore, a model only including non-genetic
      factors and the breed composition could be excluded.

PMID- 17555046
TI  - [Evaluation of the diagnosis of subclinical endometritis in dairy cattle using
      ultrasound].
AB  - The aim of this study was to determine signs of subclinical endometritis found by
      ultrasound that are associated with reduced fertility in dairy cows. The maximum
      diameter of the uterine lumen was determined by ultrasound in 324 cows without
      clinical signs of endometritis after evaluation of the genital tract 21 to 27
      days postpartum. Cows were classified into healthy or with subclinical
      endometritis by three threshold values for the maximum uterine lumen diameter of
      0.2 cm, 0.5 cm or 0.8 cm. Examinations by rectal palpation and ultrasound as well
      as classifications were repeated 14 days later. In addition, ovaries were scanned
      by ultrasound to determine the stage of the estrous cycle. In a subgroup of 103
      cows the echotexture of the uterus and its contents was evaluated. In these cows
      the diagnosis of subclinical endometritis was performed by a scoring system. The
      diameter of the uterine lumen was significantly affected by stage of the estrous
      cycle at the time of examination. However, no effects were found for the stage of
      the cycle at the time of examination on subsequent reproductive performance. A
      uterine lumen with a maximum diameter of more than 0.2 cm showed a significant
      negative association with conception rate and proportion of cows pregnant.
      Classification based on higher threshold values did not reveal an association
      with reproductive performance. Echogenic content in the uterus also decreased
      reproductive performance. A classification based on the echotexture of the uterus
      and its contents revealed significant differences between healthy cows and cows
      with subclinical endometritis regarding the proportion of cows inseminated and
      pregnant. The results of this study showed that the diagnostic of bovine
      endometritis should be broadend by ultrasonography. The definition of subclinical
      endometritis diagnosed by means of ultrasonography has to be evaluated in further
      studies.

PMID- 17555047
TI  - [Subclinical endometritis in dairy cattle and its effect on fertility--a review
      of recent publications].
AB  - Reduced reproductive performance in dairy cattle is often caused by uterine
      disorders. Beside acute metritis and chronic endometritis recent reports on a
      negative impact of subclinical endometritis on reproductive performance have been
      published. Diagnosis of subclinical endometritis can be performed by
      ultrasonography or cytological examination of the uterus. The cytological
      examination is based on uterine lavage or the cytobrush-method. Prevalence of
      subclinical endometritis in different studies ranges from 16 to 90 percent and
      depends on the diagnostic method and the time postpartum when the examination is
      performed. Affected cows showed significantly decreased conception rates,
      prolonged days to first service and days open as well as a reduced number of cows
      pregnant. Studies on the treatment of subclinical endometritis with prostaglandin
      F2alpha or analogues, intrauterine antibiotics or proteolytic enzymes showed
      heterogeneous results and do not allows valid recommendations for veterinary
      practice.

PMID- 17555048
TI  - [Radiation exposure of the pet owner during standardised X-ray diagnostic
      examinations of dogs and cats].
AB  - In Germany pet owners are present during X-ray examinations of dogs and cats. Due
      to a change in the German X-ray Ordinance and the directive "Radiation Protection
      in Veterinary Medicine" it is necessary to determine the body dose of the pet
      owners. This study in the Clinic for Small Animals includes at least ten
      measurements for each of thirteen X-ray examinations of a dog and four of a cat.
      The equivalent doses of eye lens, thyroid, chest, hands, gonads, and lower leg
      were measured using TLD (LiF:Mg,Cu,P). The maximum value of 52 microSv was
      measured on the right hand. The 99 % -quantiles amount to 13 microSv for eye
      lens, 9 microSv for thyroid, 2.3 microSv for chest (under lead apron), 14 microSv
      for both hands, 2.1 microSv for gonads (under lead apron), and 2.0 microSv for
      lower leg. In every case the median and mean values at the seven measuring
      positions are lower than 2.5 microSv per radiograph. In view of the constant
      measured equivalent doses under the lead apron of less than 5 microSv for the
      trunk and gonads per X-ray examination the measurement of the personal dose of
      the pet owner during every X-ray examination of small animals is not justified.
      Alternatively, with reference to up-to-date measurements and the presented paper
      a certificate of exemption from the dose determination for pet owners could be
      applied for from the local authority.

PMID- 17555049
TI  - [Innovative prenatal diagnosis].

PMID- 17555050
TI  - [The fruits of postgenomic analysis: identification of risk factor genes for
      Crohn's disease and type 2 diabetes].

PMID- 17555051
TI  - [Sleep and dream].

PMID- 17555052
TI  - [The physiology of sleep].

PMID- 17555053
TI  - [Diagnosis of sleep disorders and daytime drowsiness].

PMID- 17555054
TI  - [The pharmacology of benzodiazepines].

PMID- 17555055
TI  - [Neuroleptics and antidepressives as hypnotics].

PMID- 17555056
TI  - [H1-antihistaminics of the first generation].

PMID- 17555057
TI  - [Botanical sedatives].

PMID- 17555058
TI  - [Melatonin, melatonin receptor agonists and tryptophan as sleep aids].

PMID- 17555059
TI  - [Drugs in the pipeline].

PMID- 17555060
TI  - [Nonpharmaceutical methods for treatment of insomnia].

PMID- 17555061
TI  - [Arum--beware of the trap!].

PMID- 17555062
TI  - Dual source CT: cardio-pulmonary applications.
AB  - Dual source CT is a last generation scanner which allows for coronary imaging
      without beta-blocker because high quality images are feasible even at high heart
      rates. Furthermore, with this equipment, dual energy becomes possible in a single
      acquisition and triple rule-out imaging can be performed in clinical routine. The
      radiation dose remains limited in comparison with single-source CT because of
      different efficient mechanisms.

PMID- 17555063
TI  - Multi-detector CT of the coronary arteries. Potential use of CT angiography and
      coronary artery calcium scoring in screening.

PMID- 17555064
TI  - Interlude: CT of Peruvian whistling bottles.

PMID- 17555065
TI  - Post-processing and display in multislice CT of the chest.
AB  - The last generations of Multi Detector Row CT (MDCT) have revolutionized the
      management of chest disease. This is especially obvious for airway and lung
      parenchyma evaluation. MDCT allows volumetric high resolution scanning with
      isotropic resolution. Thus, contiguous visualization of the lung parenchyma is
      achieved. The resulting high quality 2D and 3D reconstructions enable a
      significant improvement in the diagnostic approach. Since the lung parenchyma has
      a unique natural contrast, low and even ultra-low radiation dose scanning
      protocols may be used in routine practice. In all cases, a good signal to noise
      ratio has to be maintained combined with the best possible spatial resolution,
      allowing all types of reconstructions.

PMID- 17555066
TI  - Acute chest pain in emergency room. Preliminary findings with 40-64-slice CT ECG
      gated of the whole chest.
AB  - ECG-gated MDCT of the entire chest represents the latest technical advance in the
      diagnostic work-up of atypical chest pain. The authors report their preliminary
      experience with the use of 40 and 64-slice CT in the emergency room and recommend
      to study only patients with moderate likelihood of coronary artery disease. ECG
      gated MDCT of the entire chest will be preferentially performed on 64-slice MDCT
      rather than 40-slice MDCT because it enable to reduce the scan time (18 seconds
      versus 28 seconds acquisition time), the volume of contrast medium (82 mL + 15 mL
      versus 97 mL + 15 mL of highly concentrated contrast agent for a patient of 70
      kgs) and radiation exposure (17 mSv versus 19 mSv). Approximately 1500 to 2000 of
      images are produced and need to be analysed on a dedicated workstation by a
      radiologist expert in cardiac and thoracic disorders. At the present time, only a
      few studies exist in the literature showing some promising results but further
      large clinical studies are needed before to implement such sophisticated protocol
      in emergency room.

PMID- 17555067
TI  - [Screening of asymptomatic coronaropathy with adenosine stress myocardial
      perfusion MRI: a pilot study].
AB  - The aim of the study was to evaluate the incidence of asymptomatic coronary heart
      disease in patients with cardiovascular risk factors and evaluate the diagnostic
      value of myocardial stress perfusion magnetic resonance as screening test in
      these patients. We performed a retrospective analysis of 103 consecutive
      asymptomatic patients with at least one clinical risk factor for cardiovascular
      disease, who have undergone myocardial stress perfusion magnetic resonance. For
      respective evaluation of ischemic myocardium and infracted myocardium, magnetic
      resonance imaging protocol included the study of both myocardial viability by
      late enhancement imaging and first-pass perfusion at rest and during maximal
      stress (adenosine). The reference standard was catheter coronary angiography for
      10 patients and clinical follow-up for 93 patients. The incidence of coronary
      heart disease was 22/103 (21%), including 6/103 (6%) ischemia and 16/103 (15%)
      infarcts. Respective sensitivity, specificity, negative and positive predictive
      values for myocardial stress perfusion magnetic resonance in detecting ischemic
      myocardium were 100, 97, 67 and 100%. Myocardial stress perfusion magnetic
      resonance can be regarded and further investigated as screening test for the
      detection of asymptomatic coronary heart disease in high-risk subjects.
      Prospective studies, larger study groups and cost-effectiveness analysis are
      needed.

PMID- 17555068
TI  - Chest MSCT acquisition and injection protocols.
AB  - The past decade there has been an enormous advance in imaging technology, most
      obvious in the field of magnetic resonance imaging (MRI) and computed tomography
      (CT). Today nearly every radiology department has a multislice CT (MSCT)
      available for routine imaging, many of which are increasingly being replaced by
      last generation 16- and 64-slice CT scanners. However, the use of fast CT
      scanners requires a better insight in acquisition and contrast media injection
      protocols in order to achieve the best possible result. It is the aim of this
      article to give a review of the basic principles of CT protocol design for the
      chest and the kinetics of contrast media injection.

PMID- 17555069
TI  - Peripheral pulmonary embolism on multidetector CT pulmonary angiography.
AB  - Nowadays CT pulmonary angiography (CTPA) has been established a widely accepted
      technique for the diagnosis of pulmonary embolism (PE), based on its high
      accuracy and ability to provide alternative diagnoses such as pulmonary, pleural
      or mediastinal diseases. Since its introduction in 1992, the sensitivity and
      specificity of CTPA increased due to reduced collimation and faster rotation
      time. The main limitation of single-detector row CTPA was diagnosis of PE at the
      subsegmental level, similar to other diagnostic techniques, such as pulmonary
      angiography, V/Q lung scan and MR. The advent of multi-detector row CT technology
      has increased the analysability of pulmonary vessels distal to the segmental
      level. Multi-detector row CTPA detects more subsegmental PE than single-detector
      row CTPA. The incidence of isolated subsegmental PE is between 5-15%, depending
      of the population investigated. Currently there is no straightforward admitted
      guidelines for treatment of subsegmental PE. Indications for treatment of
      isolated subsegmental PE are reviewed.

PMID- 17555070
TI  - Primary cardiac lymphoma.
AB  - Primary cardiac lymphoma is rare. It can present with a wide variability of
      clinical symptoms frequently leading to a delay in diagnosis. We report a case of
      a primary cardiac lymphoma in a 85 year old woman. The MRI showed a large mass in
      the right atrio-ventricular groove and infiltration of the interventricular
      septum and left ventricular wall with subtle contrast enhancement, isointense
      aspect on T1 weighted and hyperintense aspect on T2 weighted sequences. Mostly
      the radiological signs are non specific. Calcification, hemorrhage, a diffuse
      infiltrative pattern with infiltration of the valves and coronary arteries and a
      left atrial localization can suggest the diagnosis.

PMID- 17555071
TI  - Integrated PET/CT in lung cancer imaging: history and technical aspects.
AB  - Integrated PET/CT is a new anatomo-metabolic imaging modality combining two
      different techniques: Computed Tomography (CT) that provides very detailed
      anatomic information and Positron Emission Tomography (PET) that provides
      metabolic information. Integrated PET/CT has several advantages. One of the
      advantages is the use of CT data for attenuation correction that is significantly
      faster compared to that in conventional PET systems. Due to the use of CT data
      for attenuation correction, artefacts can be generated on PET images related to
      the use of intravenous or oral CT contrast agents, CT beam-hardening artefacts
      due to metallic implants and motion artefacts (respiratory motion, physical bowel
      motion, cardiac motion). The purpose of this review is to discuss some technical
      considerations concerning the CT protocol that can be used for PET/CT in lung
      cancer imaging and to give a short overview of the initial results of staging of
      non-small cell lung cancer (NSCLC).

PMID- 17555072
TI  - PET-CT in chest diseases: a short overview.

PMID- 17555073
TI  - Multi-slice CT of the chest: routine and new applications.

PMID- 17555074
TI  - Myocardial delayed enhancement imaging: comparison of two-dimensional and three
      dimensional inversion prepared fast gradient echo and steady state free
      precession sequences.
AB  - We compared two-dimensional (2D) and three-dimensional (3D) inversion recovery
      prepared (IR) fast gradient echo (FGRE) and steady state free precession (SSFP)
      sequences used in myocardial delayed enhancement imaging. Twenty patients with a
      prior history of acute coronary syndrome were included in this study. Breath
      hold, ECG gated, segmented 2D and 3D IR_FGRE and SSFP sequences were acquired
      after intravenous administration of 0.15 mmol/kg gadodiamide-DTPA. Overall image
      quality, transmural extent of myocardial infarction, infarct volume, signal-to
      noise ratio (SNR), contrast-to-noise ratio (CNR) and signal intensity ratio (SIR)
      were calculated and compared for each technique. 3D IR trueFISP showed
      significantly higher mean values of SNR and CNR compared with 3D IR turboFLASH,
      2D IR turboFLASH and 2D IR trueFISP (p < 0.04 and p < 0.001). 3D IR_FGRE showed
      the second highest SNR and CNR. 3D IR_SSFP and 3D IR_FGRE allowed the imaging of
      the whole heart within a single breath-hold which reduced the imaging time
      significantly compared to 2D IR_FGRE and 2D IR_SSFP. 3D IR_SSFP and 3D IR_FGRE
      offer higher SNR, CNR and rapid acquisiton compared to 2D IR_SSFP and 2D IR_FGRE
      with adequate image quality.

PMID- 17555075
TI  - Splenic hamartoma presenting as an occasional asymptomatic finding.
AB  - We report a case of splenic hamartoma that was occasionally detected.
      Ultrasonography performed as a screening examination revealed a hypoechoic
      splenic lesion. A computed tomography and magnetic resonance examination were
      performed in order to characterize the lesion but failed to make a final
      diagnosis. An elective laparoscopic splenectomy with consecutive histologic
      examination revealed a splenic hamartoma. Splenectomy may be required for
      definite characterization of this type of splenic lesion.

PMID- 17555076
TI  - Assessment of renal graft obstruction due to ureteral inguinal hernia: US
      detection and 3D MR confirmation.
AB  - In most cases, renal graft obstruction is caused by ureteral stenosis due to
      ischemia or technical error. Exceptional cases have been published where the
      obstacle was the result of incarceration of the ureter in an inguinal hernia. We
      report a case of this type, which prompt assessment was possible due to
      ultrasound and magnetic resonance imaging with 3D reconstruction.

PMID- 17555077
TI  - Eosinophilic granuloma of the atlas and the occipital condyle in an adult.

PMID- 17555078
TI  - Lingual thyroid with cystic component.

PMID- 17555079
TI  - Gastric carcinoid tumor.

PMID- 17555080
TI  - Cement pulmonary embolism after percutaneous vertebroplasty.

PMID- 17555081
TI  - Report of visiting fellowship in abdominal radiology at the Royal Perth Hospital.

PMID- 17555082
TI  - [Effect of polychlorinated biphenyls on DNA damage induced by benzo[a]pyrene in
      HepG2 cells].
AB  - OBJECTIVE: To explore effects of polychlorinated biphenyl, PCB153 on DNA damage
      induced by benzo(a) pyrene (B[a]P) in HepG2 cells. METHODS: As target cell, HepG2
      cells were treated at the concentrations of 0.1, 1, 10 and 100 micromol/L with
      PCB153 and at the concentrations of 12.5, 25, 50 and 100 micromol/L B[a]P
      respectively. DMSO was used as solvent control. Single cell gel electrophoresis
      (SCGE) was applied for quantitative analysis of DNA damage which was caused by
      treating alone or co-treating with PCB153 and B[a]P, CYP1A1 (EROD) and CYP2B1
      (PROD) activities were detected by using fluorescence spectrophotometry. RESULTS:
      When compared with the solvent control, the DNA oliver tail moments were
      increased significantly (P < 0.01) in HepG2 cells treated with all the
      concentrations of B[a]P, while no significant DNA damage was observed in HepG2
      cells treated with all the concentrations of PCB153. When compared with B[a]P
      treated alone, the DNA oliver tail moments showed a increase tendency in HepG2
      cells co-treated with PCB153 (0.1, 1, 10 micromol/L) and B[a]P (50 micromol/L).
      But DNA oliver tail moments were increased significantly only when co-treated
      with 10 micromol/L of PCB153 and 50 micromol/L of B[a]P (P <0.01), while
      decreased significantly after co-exposuring to 100 micromol/L of PCB153 and 50
      micromol/L of B[a]P (P <0.01). All concentrations of PCB153 induced significant
      increase in EROD and PROD activities in HepG2 cells. CONCLUSION: It was suggested
      that the enhancement of DNA damage induced by B[a]P could be associated with the
      increases of CYP1A1 and CYP2B1 activities induced by PCB153 in HepG2 cells.

PMID- 17555083
TI  - [Study of susceptibility of chromosomal damage induced by vinyl chloride monomer
      associated with genetic polymorphism in APE1, XRCC1].
AB  - OBJECTIVE: To explore the relationship between genetic polymorphism of APE1,
      XRCC1 and susceptibility of chromosomal damage induced by vinyl chloride monomer
      (VCM). METHODS: 75 workers occupationally exposed to VCM were investigated.
      Chromosome damage in peripheral lymphocyte were measured by cytokinesis-block
      micronucleus (CB-MN) test. Created restriction site-restrained fragment length
      polymorphism (CRS-RFLP) and PCR-RFLP technique was applied to detect single
      nucleotide polymorphisms (SNPs) in APE1 gene (c.148) and XRCC1 gene (c. 194,
      c.280 and c. 399). RESULTS: The frequencies of the Asp and Glu alleles of APE1
      148 in our study population were 61% and 39%, respectively. The frequencies of
      occurrence of the Arg and Trp alleles of XRCC1 194 were 85% and 15%. The
      frequencies of occurrence of the Arg and His alleles of XRCC1 280 were 85% and
      15%, too. Whereas the prevalence of Arg allele was 87.0% and XRCC1 399 allele Gln
      was 13.0%. The risk of chromosomal damage induced by VCM for individuals carrying
      XRCC1 c. 194 Arg/Arg genotype was 0.6898 (95% CI 0.4997 - 0.9333, P = 0.0195) of
      those carrying Arg/Trp, Trp/Trp genotypes. The risk of chromosomal damage for
      female VCM exposure workers was 1.6000 (95% CI 1.2284 - 2.0699, P = 0.0004) of
      male workers. The haplotypes TGG/CGG and TGG/CAGCGGG were associated with the
      decreased frequencies of total micronucleus ( P < 0. 05). CONCLUSION: It was
      suggested that female workers and subjects carrying XRCC1 194 Arg/Arg genotypes
      could be higher risk of chromosomal damage when they exposed to VCM.

PMID- 17555084
TI  - [Study on acute toxicity of R, S and (R,S)-3-monchloropropane-1,2-diol].
AB  - OBJECTIVE: To investigate the acute toxicity of R,S and (R,S) -3-monchloropropane
      1,2-diol (3-MCPD). METHODS: 10,7 and 7 groups of sexually mature ICR mice were
      employed for testing the acute toxicity of R, S and (R, S)-3-MCPD, at the doses
      of 176.78, 198.43, 222.73, 250, 280.61, 314.98 and 353.55 mg/kg 396.84 mg/kg,
      445.44 mg/ kg, 499.99 mg/kg for R-3-MCPD, 89.09, 100, 112.25, 125.99, 141.42,
      158.74 and 178.18 mg/kg for S-3-MCPD and 130.25, 150, 172.75, 198.95, 229.13,
      263.88 and 303.91 mg/kg for (R,S)-3-MCPD, respectively. The mice were given three
      forms of 3-MCPD once by gavage and observed for 14 days, the lethal dose 50s (
      LD50) were calculated by the modified Karber's method, organ/body weight ratios
      were measured and morphological changes of liver and kidney were examined.
      RESULTS: The LD50 (95% CI) of R, S and (R,S)-3-MCPD were 290.54 mg/kg (280.74 -
      300.68), 117.57 mg/ kg (113.82 - 121.45) and 190.73 mg/kg (177.76, 204.59),
      respectively. The kidney/weight ratios in R-3-MCPD treated groups were higher
      than controls at the doses of 250 - 353.55 mg/kg (P < 0.05), and the brain weight
      ratios also had an significant increase in the 353.55 mg/kg, 445.44 mg/kg and
      above doses (P < 0.05). However, no significant change on organ/body weight ratio
      of any organs in S-3-MCPD treated groups were observed. The kidney/body weight
      ratio in (R,S)-3-MCPD treated groups increased significantly at the doses of
      198.95 - 303.91 mg/kg (P < 0.05), and the brain weight ratios also had a
      significant increase at the doses of 229.13 - 303.91 mg/kg. At the doses of
      353.55 - 499.99 mg/kg, R-3-MCPD caused obvious swell of liver cells and the swell
      and congestion of the liver sinus. At the dose 229.13 mg/kg and above, (R,S)-3
      MCPD also induced the swell of liver cells and congestion of the liver sinus. No
      obvious morphological changes of kidney after administration of R, S and (R,S)-3
      MCPD were observed. CONCLUSION: The results indicated that the acute toxicity of
      S-3-MCPD may be much higher than those of (R,S)-3-MCPD and R-3-MCPD and that both
      R and S seem to possess neurotoxicity.

PMID- 17555085
TI  - [Effect on the respiration of bacteria in microcosm by the disinfectant of
      chlorine].
AB  - OBJECTIVE: To observe respiratory volume of bacteria as the physiology activity
      index to evaluate the effect of sodium hypochlorite (NaClO) on the
      microenvironment. METHODS: The water and soil from Wuhan Muoshui Lake were
      selected as research object. Man-made microcosms were designed and constructed.
      The sodium hypochlorite was put into the microcosms every 24 hour for 13 days.
      The bacteria respiratory volume and the general bacterial population were
      observed. RESULTS: The results showed that the bacteria in the low-dose
      disinfectant were stimulated and its respiration volumes were increased in the
      beginning of the experiment. But several days later, the bacteria were inhibited
      or killed predominantly which led to the decrease of its respiration volumes. In
      high-dose group, the bacteria were killed obviously in the beginning and their
      respiration volumes decreased immediately. After the disinfectant was given up,
      the respiratory volume resumed gradually to the initial condition. This change
      process accorded with the general bacterial population as a whole. The
      respiratory volume of bacteria was related with the dose of disinfectant.
      CONCLUSION: The change of the respiratory volume of bacteria was related with the
      dose of sodium hypochlorite. The disinfectant effect on the metabolic activity of
      microorganism would be lighter if it under the dose 10 mg/L.

PMID- 17555086
TI  - [Effects of sodium hypochlorite on structure and function of pond microcosms].
AB  - OBJECTIVE: To study the influence of sodium hypochlorite on destruction and
      restoration of simulated pond ecosystems. METHODS: Six pond microcosms were
      established to simulate aquatic ecosystems. 0, 1, 2.5, 5.0, 10.0 and 20.0 mg/L of
      sodium hypochlorite were put in these simulated pond microcosms every 24 h for 13
      days and followed by observation for 10 days. The values of chlorine residual,
      total bacteria count, chlorophyll-a and total productivity were detected
      regularly. RESULTS: Chlorine residual increased continuously with the increase of
      doses and time course. Content of chlorophyll-a, total productivity negatively
      correlated with dose of sodium hypochlorite. 1.0 mg/L and 2.5 mg/L of sodium
      hypochlorite promoted the growth of bacteria, but 5.0 mg/L, 10.0 mg/L and 20.00
      mg/L of sodium hypochlorite could kill bacteria effectively. Under low doses of
      sodium hypochlorite (1.0, 2.5 and 5.0 mg/L), there were no influence on
      microcosms' restoration, but the high doses (10.0 mg/L and 20.0 mg/L) could
      severely damage the microcosms. CONCLUSION: According to the tendency of
      chlorophyll-a and total productivity, structure and function of every pond
      microcosm could be changed by sodium hypochlorite in this test condition, the
      influence was reversible under the doses of 1.0, 2.5 and 5.0 mg/L, but microcosms
      could not be restored under the doses of 10.0 mg/L and 20.0 mg/L.

PMID- 17555087
TI  - [Oxidative stress of human derived fetal hepatocytes induced by product of
      chlorinated drinking water (MX)].
AB  - OBJECTIVE: To study the oxidative stress induced by 3-chloro-4-( dichloromethyl)
      5-hydroxy-2 [5H]-furanone (MX) (a product of chlorinated drinking water) in human
      derived fetal hepatocytes (L-02) in vitro. METHODS: L-02 cells were treated at
      the doses of 10, 30, 100 and 300 micromol/L of MX for 24h. Malondialdehyde (MDA),
      reduced glutathione (GSH) and 8-hydroxydeoxyguanosine (8-OHdG), the
      representative of antioxidative molecules and the marker of DNA oxidative damage
      respectively, were detected in L-02 cell treated by MX. Dimethyl sulfoxide (DMSO)
      was used as solvent control. RESULTS: (1) The content of MDA was significantly
      increased in L-02 cells etreated by MX at the doses of 30, 100, 300 micromol/L in
      comparison with solvent control. (2) The level of GSH was significantly decreased
      and the level of 8-OHdG was significantly increased in L-02 cells treated by MX
      at the concentration of 100, 300 micromol/L in comparison with solvent control.
      (3) There was a striking positive association between MDA content and 8-OHdG
      level (r = 0.767, P < 0.01) and a negative association between GSH level and 8
      OHdG level (r = 0.761, P < 0.01) in L-02 cells treated by MX at the doses from 0
      to 300 micromol/L. CONCLUSION: MX could induce oxidative stress in L-02 cells
      including increases of lipid peroxidation and DNA oxidative damage, and weakened
      effect of antioxidation. DNA oxidative damage in L-02 cells might be associated
      with lipid peroxidation and the weakening of antioxidation induced by MX.

PMID- 17555088
TI  - [Study of the mechanism of thyroid hormone disrupted by pentachlorophenol in FRTL
      5 cell].
AB  - OBJECTIVE: To study the mechanism of thyroid hormone action disrupted mechanism
      by pentachlorophenol in FRTL-5 cells. METHODS: In the study solvent control group
      (DMSO), positive control group in iodide uptake measurements (perchlorate sodium)
      and three pentachlorophenol groups were designed. FRTL-5 cells were treated at
      the doses of 0.1 microg/ml, 0.3 microg/ml and 0.5 microg/ml of pentachlorophenol
      for 24 hours. The proliferation of FRTL-5 cells was assayed by 3H - TdR, and the
      concentrations of thyroglobulin in culture were assayed by RIA. In iodide uptake
      measurements, and the 125I uptake of FRTL-5 cells was tested in 12 h and 24 h.
      RESULTS: Pentachlorophenol had no effect on the proliferation of FRTL-5 cells,
      and the concentrations of thyroglobulin in culture were decreased at the levels
      of group 0.3 microg/ml and 0.5 microg/ml. The iodide uptakes of FRTL-5 cells were
      significantly increased at the levels of group 0.33 microg/ml and 0.5 microg/ml
      in 12 h. Perchlorate sodium made significant decreases of the iodide uptake of
      FRTL-5 cells in 12h and 24h. CONCLUSION: The mechanism of the thyroid hormone
      action disrupted by pentachlorophenol may be associated with descreasing
      thyroglobulin in FRTL-5 cells.

PMID- 17555089
TI  - [Effects of lead acetate on transcription activity of nuclear factor-kappaB in
      PC12 cells].
AB  - OBJECTIVE: To investigate the effects of lead acetate and inhibitor of-kappaB (NF
      kappaB), PDTC, on the transcription activity of NF-kappacB in PC12 cells.
      METHODS: PC12 cells were exposed to 0 micromol/L, 12.5 micromol/L, 25 micromol/L,
      50 micromol/L, 100 micromol/L, 200 micromol/L, 400 micromol/L, 800 micromol/L and
      1600 micromol/L lead acetate for 24 hours. The IC50 value was measured by MTT
      assay. The pNF-kappaB-Luc reporter gene plasmid was transfected into PC12 cells
      by cationic liposome, and then the cells were exposed to 100 micromol/L, 200
      micromol/L and 400 micromol/L lead acetate and different concentrations of lead
      acetate plus 100 micromol/L PDTC, respectively. The luciferase activities of the
      reporter gene were measured by luciferase assay kit after 24 hours exposure to
      lead acetate. RESULTS: The PC12 cells were exposed to lead acetate at varied
      concentrations for 24 hours, and the growth and proliferation of the cells are
      inhibited with various degrees, showing a dose-effect relationship. The IC50 was
      detected to be (533.966 +/- 100.830) micromol/L. The results showed that
      luciferase activity of PDTC control groups is lower than that of blank control
      group (P < 0.01) 24 hours after lead acetate exposure. It is also found that the
      luciferase activity of groups treated with lead acetate are higher than that of
      blank control group (P < 0.01) with a dose-effect relationship. Significantly
      higher luciferase activity are found in the groups treated with lead acetate and
      PDTC compared with the PDTC control group (P < 0.01). CONCLUSION: Lead treatment
      to PC12 cell results in activation of NF-kappaB.

PMID- 17555090
TI  - [Study on the location on the nucleotide of DNA lesion detected by RDPCR].
AB  - OBJECTIVE: To simplify the establishing procedure of RDPCR and detect the DNA
      lesion on the precise position at the level of nucleic acid. METHODS: The TK6
      cell was cultured and its genomic DNA was extracted and prepared to the single
      stranded probes of the exon 2 of k-ras gene. The exon 2 of k-ras gene was
      amplified,called short fragment. The digestion of the genomic DNA and the short
      fragment were treated by the endonuclease HinfI. To the former, the products come
      from the every step of RDPCR were imaged after gel electrophoresis (GE) and the
      end products was taken coloration after southern hybridization with the single
      stranded probes of the exon 2 of k-ras gene as well as were sequenced after re
      amplified. To the latter, the genomic DNA were treated as the former except the
      GE. RESULTS: From the image of GE, the straps could be seen clearly that come
      from every step of amplifying of short fragments which were cleaved by the
      endonuclease HinfI in RDPCR. The clear hybridized bands caused by the products of
      RDPCR were seen at the expectant position. The sequencing analysis showed that
      the position was linked by the linker was just the restriction site of HinfI.
      CONCLUSION: Results indicated that RDPCR could be easily established by the short
      fragment method. This may be the first time detect the precise position of DNA
      lesion at the level of nucleic acid by RDPCR.

PMID- 17555091
TI  - [Effect of oncolyn on activities of ATPase and neurotrophic factors expression in
      aging mice].
AB  - OBJECTIVE: To study the changes of ATPase activety and neurotrophic factor
      expression of brain in aging mice and the Oncolyn's neutralization effect.
      METHODS: Kunming mice were randomly divided into control group, aging group and
      Oncolyn group. The aging models were made by subcutaneously injecting D-galactose
      at neck skin. Oncolyn were administrated through oral for 70 days. The activity
      of ATPase in brain tissue and protein expression of NGF and BDNG in hippocampus
      were measured. RESULTS: The activities of Ca2+ -Mg2+-ATPase and Na+ -K+-ATPase in
      aging mice were significantly decreased from 0.27 and 0.046 U/mg prot (control
      group) to 0.022 and 0.021U/mg prot (P < 0.05). The protein expressions of NGF,
      BDNG also were lower than those in control group (decreased 48.28% and 43.24%
      respectively). After mice were administrated Oncolyn two kinds of ATPase
      activities were significantly increased (0.056 and 0.117 U/mg prot respectively).
      In addition, expressions of NGF, BDNG also were higher than those in aging mice
      (increased 46.67%, 163.64%). CONCLUSION: It was seemed that Oncolyn could
      neutralize aging through increasing of ATPase activity and neurotrophic factor
      expression in the process of aging.

PMID- 17555092
TI  - [Study of genetic polymorphism of heat shock protein 70-1 associated with
      susceptibility to ischemic stroke].
AB  - OBJECTIVE: To explore the association between gene polymorphism of heat shock
      protein 70-1 (HSP 70-1) and the susceptibility to ischemic stroke. METHODS: A 1:1
      matched case-control study was conducted. 116 patients with ischemic stroke were
      selected from two general hospitals in Shenzhen. The controls were selected by
      the same gender and ethnic group, and each pair's ages were permitted to differ
      within 5 years. HSP70-1 genotypes were determined by using the polymerase chain
      reaction-restriction fragment length polymorphism (PCR-RFLP) technique. The cases
      and controls were interviewed using the same questionnaire. RESULTS: There were
      significant differences in the distribution of genotypes and allele frequencies
      between the case group and control group (P < 0.05). The allele frequencies of
      HSP70-1 b2 in case group (36.64 %) were higher than those in the control (21.99%)
      (P < 0.005). Results of conditional logistic regression demonstrated that HSP70,
      hypertension and smoking were independent risk factors of ischemic stroke, and
      their OR values were 5.41, 2.79 and 8.17, respectively. Tea drinking history was
      a protective factor, and the OR value was 0.18. CONCLUSION: It was suggested that
      polymorphism of HSP70-1 gene should contribute to the higher risk of ischemic
      stroke.

PMID- 17555093
TI  - [Effect of chronic ethanol intake on insulin receptor, insulin receptor subsrate
      1 and phosphoinositide 3-kinase mRNA expression in skeletal muscle of rats].
AB  - OBJECTIVE: To study the effect of chronic ethanol intake on insulin receptor
      (IR), insulin receptor substrate-1 (IRS-1) and p85 subunit of phosphoinositide 3
      kinase (PI-3K) mRNA expression in skeletal muscle of rats and explore the
      molecular mechanism of ethanol induced insulin resistance. METHODS: 80 Wistar
      rats were randomly divided into four groups on the basis of body weight: control
      (C) group, low (L), moderate (M) and high (H) ethanol group. Each group was
      comprised of 10 male and 10 female rats. Rats were given ethanol in different
      concentration of (10%, 20% and 33%) through intragastric-feeding and ethanol
      doses was 10 ml/kg bw per day. After 19 weeks treatment, fasting plasma glucose
      and insulin were measured. HOMA-IR index of each group were calculated. The
      expression of IR, IRS-1 and PI-3K (p85) mRNA in skeletal muscle were detected by
      RT-PCR. RESULTS: In male rats, the fasting plasma glucose of group H, fasting
      plasma insulin of group L, M and HOMA-IR indexes of all ethanol-fed groups were
      higher than those of group C (P < 0.05). The levels of IR mRNA of group L and H
      was lower, while increasing with the ethanol doses, IRS-1 and PI-3K(p85) mRNA
      expression increased first, then was decreased (P < 0.05). In female rats, in
      comparation with group C, the fasting plasma glucose of group H was higher, while
      fasting plasma insulin was lower, the levels of IR, IRS-1, PI-3K(p85) mRNA of
      group H and M were suppressed (P < 0.05). HOMA-IR indexes had on differences in
      the four groups of female rats (P > 0.05). CONCLUSION: The present results
      suggested that chronic ethanol intake could induce insulin resistance and down
      regulated the expression of IR, IRS-land PI-3K mRNA in skeletal muscle could be
      the molecular mechanism.

PMID- 17555095
TI  - [Effects of vitamin B12 on ethanol-induced mouse embryonic abnormality in vitro].
AB  - OBJECTIVE: To evaluate the developmental improvement of vitamin B12 on ethanol
      induced embryonic abnormality in vitro. METHODS: Whole embryo culture system was
      used in this study. Early somite stage (GD8.5) mouse embryo was explanted and
      cultured in rat serum medium (immediately centrifugal serum, ICS) with vitamin
      B12 (0, 10(-6), 10(-5) and 10(-4) mol/L) and ethanol (4.0 g/L) for 48h to
      evaluate the embryo development and morphological differentiation. RESULTS:
      Developments of crown-rump length, head length and somite number were
      significantly improved at the concentration of 10(-5) mol/L vitamin B12 (P <
      0.05) and the indexes of embryonic growth and development except allantoid,
      heart, maxillary and mandible significantly increased at the concentration of 10(
      4) mol/L vitamin B12 (P < 0.05), which were all compared with the positive group.
      CONCLUSION: Vitamin B12 could improve ethanol-induced developmental toxicity in
      mice in vitro.

PMID- 17555094
TI  - [Effects of iodine excess and selenium supplement on the levels of thyroid
      hormone and its receptor expression in filial cerebrum of mice].
AB  - OBJECTIVE: To study effects of iodine excess on the levels of serum T4 and T3 and
      TRalpha1 and TRbeta1 expression in the cerebrum of filial mice and the supplement
      of selenium. METHODS: Sixty BALB/c mice were divided randomly into four groups:
      control group (tap water, NC), iodine excess group (3000 microg/L I, EI +),
      selenium supplement group (200 microg/L Se, Se +) and iodine excess plus selenium
      (3000 microg/L + I 200 microg/L Se, EI + Se +) group. The mice were mated at the
      end of the fourth month. Serum T4 and T3 were determined on postnatal day 14 and
      28. The expression levels of TRalpha1 and TRbeta1 mRNA in filial mice cerebrum
      were detected by fluor scent real time PCR. RESULTS: Serum T4 level in EI + was
      lower significantly than that in NC and EI + Se + on postnatal day 14. mRNA
      levels of TRalpha1 and TRbeta1 in EI + were higher than those in other groups on
      postnatal day 0 and 28. No significant difference in serum T4 level and TRalpha1
      and TRbeta1 mRNA expression level between four group on postnatal day 28.
      CONCLUSION: The expression of TRalpha1 and TRbeta1 infilial mice cerebrum could
      be up-regulated by iodine excess intake and could be alleviated by selenium
      supplement.

PMID- 17555096
TI  - [Staphylococcus aureus in food determined by polymerase chain reaction].
AB  - OBJECTIVE: To establish a rapid polymerase chain reaction (PCR)method for
      detection of staphylococcus aureus in milk, ice cream and meat. METHODS: Two
      pairs of oligonucleotide primers were designed with thermo nuclease gene nuc and
      surfaced-associated fibrinogen-binding protein gene ClfA to detect staphylococcus
      aureus. Fifty-two staphylococcus aureus and thirty-one non staphylococcus aureus
      were amplified by PCR to verify the specificity. Various numbers of bacteria were
      added into milk, ice cream and meat. After enrichment, DNA extracted in different
      time was amplified by PCR to verify detection limit. RESULTS: Each primer pair
      allows specific detection. The limit of detection was 10 cfu/g (ml) in three
      kinds of food. Whole procedure of detection could be finished in 24 hours.
      CONCLUSION: A rapid, sensitive and specific PCR method can be applied detecting
      staphylococcus aureus in milk, ice cream and meat.

PMID- 17555097
TI  - [The use of ultrasensitive time-resolved fluoroimmunoassay for rapid detection of
      microcystin LR].
AB  - OBJECTIVE: In order to provide a rapid and selectivity method for the
      determination of microcystin LR (MCLR). METHODS: An indirect competitive time
      resolved fluoroimmunoassay (TRFIA) was developed. MC-LR-BSA was coated by
      physical adsorption onto the microtitre plate, MC-LR or sample with MC-LR as a
      competitor. Both them were incubated with limited anti- MC-LR antibody. and a
      goat antirabbit IgG-Eu3+ conjugate was used as a tracer. RESULTS: The sensitivity
      of MC-LR-TRFIA was 0.01 microg/L, and the recovery rate was 99.7%. RSD of CBL
      TRFIA were 3.9%. The sensitivity of MC-LR -TRFIA provided a linear reaponse from
      0.01 - 20 microg/L, with ED50 of 0.57 microg/L or ED80 of 0.16 microg/L and ED20
      of 1.70 microg/L. The cross reactivity of the MC-LR-TRFIA with MC-LF and MC-RR
      was 0.73% and 35%. Both MC-LR-TRFIA and MC-LR-ELISA test were applied for the
      quantitative measurement of MC-LR in the same samples, and the coefficient of
      correlation was 0.958. CONCLUSION: The method is suitable to determine MC-LR in
      water samples.

PMID- 17555098
TI  - [Preparation and identification of a monoclonal antibody against citrinin].
AB  - OBJECTIVE: To prepare the monoclonal antibody (McAb) against citrinin. METHODS:
      Four citrinin-protein conjugates (A, B, C and D) were synthesized by the active
      ester, Munnich Reaction and 1,1-carbonyldiimidazole (CDI) method, respectively.
      BALB/c mice were immunized with the conjugates for producing the McAb against
      citrinin. RESULTS: The antibodies against citrinin have been produced in serum of
      immunized BALB/c mice with the conjugate C. A McAb against citrinin was acquired
      according to the traditional procedure. Cross reactivity of the McAb was less
      than 0.01% with ochratoxin A, patulin, aflatoxin B1, deoxynivalenol and
      zearalenone, respectively. A competitive enzyme-linked immunosorbent assay was
      developed. The linear range of ELISA was between 20 ng/ml and 1 000 ng/ml, the
      detectable limit was 10 ng/ml. Recovery of citrinin from wheat spiked with
      citrinin was from 95% to 112%, the coefficient of variation was 12.2% to 20.4%.
      CONCLUSION: The McAb against citrinin was acquired successfully.

PMID- 17555099
TI  - [Study on the prevalence of goiter associated with some factors in Guangzhou
      elderly population].
AB  - OBJECTIVE: To study the prevalence of goiter associated with some factors in
      Guangzhou after the implementation of universal salt iodization. METHODS: With
      cross-sectional study, the electronic questionnaire was used to investigate basic
      demographic indexes, socioeconomic indexes and the history of thyroid diseases in
      10305 Guangzhou elderly people who aged 50 and more by face to face interview.
      The prevalence of goiter was got by thyroid palpation, and the relationship
      between the prevalence and factors mentioned above was analyzed. Chi-square test
      was used to test the difference of the rates, and Logistic regression model was
      used to do multi-factors analysis. RESULTS: (1) Overall, 442 cases of thyroid
      large were found, including I grade 330, formed 74.7%, and II grade 112, formed
      25.3%. The prevalences in total, female and male were 4.3%, 5.1% (369 cases) and
      2.4% (73 cases) respectively. The prevalence was significantly higher in the
      female than that in the male. (2) The results of multi-Logistic regression showed
      that gender, history of thyroid diseases and education were the main impact
      factors. The risks suffered from goiter in the female, in those who had ever
      suffered from thyroid diseases and in those who were middle school education and
      higher were more 1.81 times, 5.43 times and 1.25 times than those in the male in
      those who had never suffered from thyroid diseases and in those who were primary
      school education and lower respectively. CONCLUSION: The iodine nutrition of
      Guangzhou elderly population was fairly moderate. Female and those who had ever
      suffered from thyroid diseases got a higher risk suffering from goiter.

PMID- 17555100
TI  - [College students social anxiety associated with stress and mental health].
AB  - OBJECTIVE: To explore the mediator effects of social anxiety on college students'
      life stress and mental health. METHODS: 1430 college students were tested by
      revised Adolescent Self-Rating Life Events Check List (ASLEC), General Health
      Questionnaire (GHQ12) and social anxiety scale chose from Self-Consciousness
      Scale. RESULTS: 1. Social anxiety was the mediator variable between stress and
      mental health. 2. Female students were easily suffered from higher losing stress
      and human relationship stress in comparision with male. 3. Non-only child
      Students got a higher score in social anxiety and lower GHQ in comparision with
      only child. CONCLUSION: It may be helpful to improve the stress management and
      mental health of college students by testing and intervening their social anxiety
      perception.

PMID- 17555101
TI  - [Survey on the status of dietary vitamin a intakes in Chinese residents].
AB  - OBJECTIVE: To describe the intake status of dietary vitamin A and the trends of
      the intakes from 1982 to 2002 in Chinese residents. METHODS: This paper was based
      on the data collected in "the Nutrition and Health Status of the Chinese People
      in 2002". The subjects in the dietary survey were 68 965 residents from 23 470
      households. RESULTS: The average retinol equivalent intake in per day was 469.2
      microg for per reference man. The residents with the retinol equivalent intake
      equal or higher than RNI accounted for 14.5% and those with the intake lower than
      20% of the RNI accounted for 23.2%. The retinol equivalent intake in type III
      rural areas was the lowest among all the areas with only 9.7% residents having
      intakes equal or higher than RNI. The intakes of the retinol equivalent increased
      with the mounting of income level. The average retinol equivalent intake was not
      seen improved during the past twenty years. CONCLUSION: The dietary intake of
      vitamin A could be lower in Chinese residents.

PMID- 17555102
TI  - [Analysis of children's nutritional status based on WHO children growth standard
      in China].
AB  - OBJECTIVE: To compare children's growth patterns and estimates of malnutrition
      using the WHO standards versus the NCHS reference in China. METHODS: Data
      originated from China children nutrition surveillance in 2005, Z-scores and
      prevalence of malnutrition were compared between standards. RESULTS: There was
      substantial difference in Z-scores between standards in rural (P < 0.0001).
      According to the WHO standards, prevalence of underweight in rural was lower than
      that of underweight based on the NCHS reference (6.1% . vs. 8.6%, P < 0.0001).
      Except for children under 6 months, all age groups underweight rates were lower
      according to the WHO standards. Prevalence of stunting in rural was higher based
      on the WHO standards (16.3% . vs. 13.0%, P < 0.0001), prevalences of stunting
      under 6 months were 2.1 times of that based on NCHS reference. As for wasting,
      there were no differences between standards, but wasting was substantially higher
      during the first half of infancy. Overweight rates based on the WHO standards
      were higher than those based on NCHS reference in urban (6.7% . vs. 5.4%, P <
      0.0001). CONCLUSION: In comparison with NCHS reference, population estimates of
      malnutrition would vary by age, growth indicator based on WHO standards. The WHO
      standards could provide a better tool to monitor the rapid and changing rate of
      growth in early infancy, further analysis on existing data was needed.

PMID- 17555103
TI  - [Analysis on the changes of nutritional status in China--the improvement of
      complementary feeding among Chinese infants and young children].
AB  - OBJECTIVE: To describe the improvement of complementary feeding during year 1992
      to 2005. METHOD: The datasets of 1992, 2000 and 2005 China Food and Nutrition
      Surveillance System (CFNSS) were used, the improvement of complementary feeding
      were presented in terms of timely introduction, and frequency of food items in
      complementary feeding, Logistic Regression Analysis on the relationship of child
      growth with complementary feeding pattern were conducted. RESULTS: The
      complementary feeding of Chinese children improved substantially during year 1992
      to 2005. The appearance of animal food, vegetable/fruit and milk in complementary
      feeding was negatively correlated with the prevalence of stunting and
      underweight. OR of non-milk complementary food for stunting at age 9 - 24 month
      was 1.378, to underweight, the OR was 1.189. The results of multiple regression
      analysis proved the frequency of feeding vegetable/fruit, animal food and milk
      played essential role in child growth during 6 - 24 month of age. CONCLUSION: The
      improvement of complementary feeding contributed substantially to the improvement
      of child growth in past decade in China.

PMID- 17555104
TI  - [Analysis on the changes of nutritional status in China anemia status of children
      under 5 in China].
AB  - OBJECTIVE: To provide the evidence to policy-maker for further improving child
      nutrition status in China based on the data of Chinese Food and Nutrition
      Surveillance System. METHODS: To measure the content of Haemoglobin by
      Cyanmethemoglobin and HemoCue, The diagnostic criterion is 110 g/L for child aged
      6 months to under 6, proposed by WHO and UNICEF, with adjustment for population
      living in high altitude over 1000m. To study on relationship between child anemia
      and mother anemia by measurement haemoglobin for children and their mother.
      RESULTS: There is basically no change in anemia prevalence of children under 5 in
      1992 - 2005. Prevalence of anemia is varying along with ages. The peak of anemia
      prevalence is 6 - 12 months. The related risk of anemia of mother and child
      anemia. is 2.31. The prevalence of diarrhea will increase by child anemia. Anemic
      mothers, breastfeeding, stunting, LBW and quality of complementary food are
      related factors of anemia of children aged 4 - 23 month. But only anemia of
      mothers and stunting are related to anemia of children aged 24 - 59 month.
      CONCLUSION: The necessary actions should be taken for improvement of anemia of
      children and mother simultaneously.

PMID- 17555105
TI  - [Measuring the percent body fat of overweight and obese schoolchildren in Beijing
      -bioimpedance analysis (BIA)].
AB  - OBJECTIVE: To measure the percent body fat (fat%) of overweight and obese urban
      schoolchildren in Beijing, and provide data for making clinical criteria in
      childhood obesity diagnosis. METHODS: A cross-sectional study of 681 children at
      the ages of 7 - 11 years were selected in two typical public primary schools in
      Beijing urban area. Among them, there were 338 boys (49.6%) with average age (9.4
      +/- 1.4) years old, and 343 girls average age (9.3 +/- 1.4) years old. Fat% was
      measured by using bioimpedance analysis (TBF-026). "Reference norm for screening
      overweight and obesity in Chinese children and adolescents" was used to identify
      overweight and obese children, differences in fat% between any two groups were
      analyzed. By using Mann-Whitney U of non-parametric tests. RESULTS: The median
      and interquartile range of fat% in normal non-obese, overweight and obese boys or
      in the girls were 15.8% (13.0% - 18.2%), 21.8% (19.4% - 26.1%) and 29.6% (25.1% -
      34.3%),and were 15.5% (12.2% - 19.3%), 25.2% (21.1% - 27.5%) and 30.5% (28.2% -
      34.8%), respectively. There were significant differences in fat% in different
      body types (P < 0.01). CONCLUSION: Fat% in overweight and obese schoolchildren in
      Beijing urban was about 20%, and was compared to other ethnical schoolchildren in
      the world.

PMID- 17555106
TI  - [Construction of CYP1A1-Wt and Asn461, Val462 gene eukaryotic expression vector
      and itstransfection in HLF cells].
AB  - OBJECTIVE: To establish the cells model with high expression CYP1A1 and analyze
      the expression of the variable genotype. METHODS: Clone the target fragment
      (CYP1A1-Wt, Asn461, and -Val462) in T-Vectors into pBABE-neo, then transfer into
      the human embryonic lung fibroblast cells (HLF). The positive cells were selected
      by G418. The expression of CYP1A1 protein was measured by Western-Blot. At the
      same time, cells shape, growth of curve, and carcinogenicity were observed.
      RESULTS: HLF transferred with wild-CYP1A1 and variant-CYP1A1 expressed CYP1A1
      protein higher than normal HLF. No differences of biology were found between the
      transfected HLF and normal HLF. These cells are not belong to carcinogenesis
      cells. CONCLUSION: HLF cells with wild-CYP1A1 or variant-CYP1A1 ware established
      successfully.

PMID- 17555107
TI  - [Comparison of the acrylamide level in microwaved popcorn with that of ordinarily
      heated one].
AB  - OBJECTIVE: To establish a method of examining acrylamide in cooked popcorn.
      METHODS: Solid phase extraction/gas chromatography (SPE/GC) was established with
      N, N-dimethyl acrylamide as internal standard. RESULTS: The detection limit and
      the quantification limit were estimated at 3 microg/L and 10 microg/L,
      respectively, and the linear correlation coefficient was 0.9969. Seven commercial
      popcorn samples with different flavors were collected and tested in this paper.
      The RSD of acrylamide level of caramel sweet popcorn microwaved was 1.95 % (n =
      6). When the commercial popcorns of caramel sweet and cream salted were
      microwaved (A and D) or conventional heated (A' and D'), the acrylamide levels
      reached [Am]A = 1017 microg/kg, [Am]D = 146.5 microg/kg, [Am]A, = 2206 microg/kg
      and [Am]D = 970.1 microg/kg, respectively. CONCLUSION: The microwaved popcorns
      tested are safer in general because the acrylamide level of them except that with
      high simple sugar content is obviously lower than that of ordinarily heated one.

PMID- 17555108
TI  - [Effect of various cooking methods on the contents of major flavonoids in
      vegetables].
AB  - OBJECTIVE: To investigate the effect of various cooking methods on the contents
      of major flavonoids in vegetables, and to provide basic data for researches on
      the relationship between flavonoid and health. METHODS: Nine kinds of vegetables
      obtained from Tianjin market were cooked by frying, boiling, stewing, microwave
      cooking respectively, then the contents of flavonoids in vegetables and soups
      after cooking were determined by HPLC. RESULTS: The reserving rates of flavonoids
      after frying, boiling, stewing and microwave cooking ranged from 54.6% to 115.6%,
      33.6% to 107.8%, 31.7% to 100.5%, and 43.1% to 109.6% respectively. Parts of
      flavonoids were also transfered to the soup after cooking. The transferring rate
      ranged from 1.4% to 55.8%. CONCLUSION: Cooking often affected the flavonoids in
      vegetables in some degree, and various cooking methods exerted different effects
      on the content of flavonoids.

PMID- 17555109
TI  - [Effect of the diet from Yanting region on proliferation of human esophageal
      cancer cell line].
AB  - OBJECTIVE: Sero-physiology method was used to observe the effects of sera from
      rats fed the diet of Yanting (high prevalence region of esophageal cancer) on
      proliferation of human esophageal cancer cell Eca-109. METHODS: Male SD rats was
      submitted to three experimental diets. A standard diet, the healthy adults' diet
      and the Yanting's diet were fed for seven days. Body weights and diet intakes
      were measured every day. Methyl thiazolyl tetrazolium (MTT) assay were used to
      explore the optimal conditions of rats'sera culturing the cell Eca-109. Human
      normal liver epithelial cell (HL7702) and 10% deactivated bovine serum were
      respectively set as normal cell control and serum control. The effects of sera
      from rats fed the Yanting's diet on Eca-109 were observed by means of cell growth
      curve, cell doubling time analysis and 3H-thymidine incorporation. RESULTS: No
      significant differences of diet intakes and body weights between the rats fed the
      standard diet and the healthy adult diet were found. It was demonstrated that 5%
      non-deactivated rats' sera could replace 10% deactivated bovine serum in medium
      for culturing human esophageal cancer cell Eca-109. Contrast to the other three
      controls, sera from rats fed the Yanting's diet significantly promoted Eca-109
      cells proliferation, while showed inhibitory effect on human normal liver
      epithelial cell (HL7702). CONCLUSION: The results showed that the diet of high
      prevalence region of Janting esophageal cancer could significantly promote the
      proliferation of human esophageal cancer cell Eca-109.

PMID- 17555110
TI  - [Research advance on relation between humic acid and chondrocyte injuries].
AB  - Kashin-Beck disease (KBD) is a chronic osteoarthritic disease, and a endemic in
      parts of China, its etiology is unknown. Humic substance in drinking water has
      been proposed as one of the causative factors of KBD. At present, many studies on
      humic acid and chondrocyte injuries were reported. In this article, the progress
      of humic acid and chondrocyte injuries were reviewed.

PMID- 17555111
TI  - [Techniques of separation and identification of enterohemorrhagic Escherichia
      coli O157 in laboratory].
AB  - Escherichia coli O157 is an important food-borne human pathogen. Separation and
      identification of this bacterium and further research in molecular level could
      have important significance. The techniques of separation and identification of
      E. coli O157 in laboratory, such as plate separation, immunomagnetic separation,
      and polymerase chain reaction were reviewed, and made a comparision of various
      methods.

PMID- 17555112
TI  - [Supervision of genetically modified foods by the international community].
AB  - The genetically modified foods (GMF) are latent with great commercial
      potentiality and related with public health. The international organizations and
      the governments have been attached important to it and constituted correlative
      statutes. The article is intended to introduce the development of GMF, review
      some correlative statutes about GMF supervision by the international
      organizations and the governments. It is significant to constitute and consummate
      the law system of GMF in our country.

PMID- 17555113
TI  - [Research advance of environmental cadmium exposure on human health damage].
AB  - Based on the available data of population survey, we review the research
      situation of health hazards on the environment cadmium polluted population from
      the threshold study of cadmium burden on human body, the chronic hazards of
      cadmium pollution on human health, the identification diagnosis of cadmium
      hazards. The information in this review could provide ideas for future study goal
      and development trend of health hazards in environmental cadmium pollution.

PMID- 17555114
TI  - [Anemia in chronic lymphatic leukemia: is erythropoietin the solution?].
AB  - Anemia is a common complication in the clinical course of chronic lymphocytic
      leukemia. Low hemoglobin levels both correlate with an adverse prognosis and
      adversely affect the quality of life of chronic lymphocytic leukemia patients.
      Different physiopathological phenomena may lead to anemia: marrow infiltration,
      hypersplenism, immune hemolysis or toxicity of chemotherapy. Treatment with human
      recombinant erythropoietic agents has been shown to be effective for anemia
      associated with different lymphoproliferative syndromes. This paper analyses the
      available evidence on erythropoietic agent treatment for chronic lymphocytic
      leukemia associated anemia. The comparative effect of different dosage schemes,
      the role of possible response-prediction factors such as the endogenous
      erythropoietin level and the results achieved using darbopoietin alpha are
      reviewed.

PMID- 17555115
TI  - [Diagnosis and management of deep venous thrombosis].
AB  - Deep-vein thrombosis (DVT) is a common condition that can lead to complications
      such as postphlebitic syndrome, pulmonary embolism and death. Currently, an
      algorithm strategy combining pretest probability, D-dimer testing and compression
      ultrasonography imaging allows for safe and convenient estimation of suspected
      lower-limb thrombosis. The mainstay of treatment is anticoagulation therapy. The
      use of low-molecular-weight heparin or pentasaccharide (fondaparinux) allows for
      outpatient management of most patients with DVT. The duration of anticoagulation
      depends on whether the primary event was idiopathic or secondary to a transient
      risk factor. Interventions such as thrombolysis and placement of inferior vena
      cava filter are reserved for special situations.

PMID- 17555116
TI  - [Management of subclinical hyperthyroidism].
AB  - Management of subclinical hyperthyroidism (low TSH and normal thyroid hormones)
      is controversial. Knowledge of its causes, clinical context and associated
      morbidity is required. It is recommended to follow six steps in exploration and
      treatment: 1) confirmation, 2) estimation of severity, 3) cause assessment, 4)
      study of complications, 5) balance whether treatment is needed and 6) if
      necessary, choice of the most appropriate form. In its management, the same
      treatments are used as in overt hyperthyroidism.

PMID- 17555117
TI  - [Antiplatelets and anticoagulants in acute coronary syndromes: levels of
      evidence].
AB  - Management of acute coronary syndromes (ACS) has moved rapidly in parallel with
      our understanding of the pathophysiological basis of the disease. In the
      eighties, the demonstration of the pivotal role of coronary thrombosis in the
      etiology of a ACS led to administration of aspirin and unfractionated heparin. In
      recent years, new medical and invasive therapies have been developed: anti
      platelets (thienopyridines and glycoprotein Ilb/IlIa inhibitors), antithrombins
      (low molecularweight heparins) and most recently, factor Xa inhibitors
      (pentasaccharides). As new treatments are rapidly added, clinicians are
      constantly challenged to incorporate new information and guidelines into their
      practices in a timely fashion.

PMID- 17555118
TI  - [From the head to the feet].

PMID- 17555119
TI  - [The dignity of the frozen human embryo].
AB  - PURPOSE: The issue of the dignity of the human embryo is one of the key questions
      in bioethics debate today. The human being's dignity lies in the original and
      unique individuality that every embryo has. If there is no respect and defense of
      the human body from the very first moment of its appearance, it is impossible to
      assert the dignity of any human being. For this reason, it does not seem good for
      human dignity that human beings, in their incipient phase, should suffer from the
      halting of their biological functions. The practice of cryopreservation of human
      embryos shows a loss of the sense of the value of each individual human being.
      METHODS: This paper is developed from a descriptive and interdisciplinary study
      of key ethical concepts in this subject. CONCLUSIONS: 1. Respect for the embryo's
      dignity must indeed exist from the beginning of its life. 2. For this reason,
      this respect does not depend on any operation, but on the eminence of its being.
      3. Not only is freezing a habitat which contradicts the dignity of life, but it
      is also the expression of a will that determines and decides the human life of
      weaker beings. The embryo's dignity is thus reduced to the value of use where it
      is not out of date.

PMID- 17555120
TI  - [Genetic markers in population studies of atlantic salmon Salmo salar L: analysis
      of DNA sequences].
AB  - The review, which consist of two parts, summarizes literature data on all genetic
      markers used in population studies of Atlantic salmon. the second part of the
      review concerns analysis of DNA sequences: fragments of known genes, anonymous
      genome sequences, mini- and microsatellites, mitochondrial DNA. The main results
      of studies of the Atlantic salmon gene poll using DNA markers are discussed. Most
      of the markers examined in certain conditions may be under selection. The
      resolution power of various methods of DNA analysis and the fields of their use
      are considered in reference to Atlantic salmon.

PMID- 17555121
TI  - [Cytoplasmic male sterility and restoration of pollen fertility in higher
      plants].
AB  - The review deals with cytoplasmic male sterility (CMS) in higher plants:
      impairment of the pollen formation resulting from interaction of the nuclear and
      mitochondrial genomes. The information on the known nuclear restorer-of-fertility
      genes and their effects on the expression of CMS-associated mitochondrial loci
      are considered. Heteroplasmy of mtDNA in plants and its potential association
      with CMS inheritance, as well as possible mechanisms of the observed direct and
      reverse association between altered expression of the CMS-inducing mitochondrial
      genome, metabolic defects, and pollen sterility are discussed.

PMID- 17555122
TI  - [Genetic control of the spring habit in old local cultivars and landraces of
      common wheat from Siberia].
AB  - The inheritance of the spring habit was studied in 63 old local cultivars and
      landraces of common wheat from Eastern and Western Siberia and the Tyva Republic.
      Minimal polymorphism was observed for the dominant Vrn genes, controlling the
      spring habit in landraces of these regions. The control was digenic and involved
      the Vrnl and Vrn2 dominant genes in the majority (95%) of cultivars and was
      monogenic in three cultivars. None of the cultivars had the Vrn3 dominant gene,
      characteristic of the neighboring regions of China and Central Asia. Among 137
      old local cultivars and landraces of Siberia, only one (cultivar Sibirskaya (k
      23347) from Irkutsk oblast, was comparable in the response to the natural short
      day (photoperiod) to Chinese cultivars. Comparison of the results and the data
      reported for commercial cultivars revealed that the genotype frequencies of the
      dominant Vrn genes in Siberian landraces and commercial cultivars of common wheat
      remained essentially unchanged at least for the past 100 years. At the same time,
      Siberian landraces significantly differed in Vrn dominant gene frequencies from
      cultivars of the adjacent regions. It was assumed that the control of the spring
      habit by the two Vrn dominant genes is optimal for the climatic conditions of
      Siberia.

PMID- 17555123
TI  - [The carbohydrate-binding sequences in lectins of the clovers trifolium repens,
      T. pratense, and T. trichocephalum].
AB  - The carbohydrate-binding sequences (CBS) in the lectin genes of Trijilium repens,
      T. pratense, and T. tri-chocephalum were sequenced. The gene regions encoding
      lectin CBS of T. pratense and T. repens displayed a considerable similarity;
      however, the CBS of these species differed essentially. Moreover, T. repens
      formed a compact cluster with Melilotus albus and M. officinalis in the
      phylogenetic trees constructed according to the nucleotide sequences and the
      corresponding CBS of legume lectins. T. trichocephalum does not fall into the
      group of the tribe Trifolieae members according to both the amino acid sequence
      of lectin carbohydrate-binding region and the nucleotide sequence of lectin gene.

PMID- 17555124
TI  - [Cloning and analysis of the resistance gene fragments from silverleaf sunflower
      Helianthus agrophyllus].
AB  - Using a combination of degenerate primers designed from the NBS domains of the
      resistance genes, amplification and subsequent cloning of the resistance gene
      fragments from sunflower (Helianthus agrophyllus) was conducted. Sequences of
      cloned PCR products differed from one another and displayed homology to NBS
      domain fragments of the already known plant resistance genes, as well as to the
      analogous genes from different classes. The highest homology was shown to the NBS
      domain regions of cultivated sunflower and the other members of the family
      Compositae. Two cloned fragments had open reading frames, while the other
      sequences carried stop codons and seemed to belong to pseudogenes. Amino acid
      sequences of Helianthus agrophyllus analyzed contained conservative regions
      typical of NBS domains of the resistance gene products.

PMID- 17555125
TI  - [Genetic variation and differentiation in population of Japanese emperor oak
      (Quercus dentata Thunb.) and Mongolian oak (quercus mongolica fisch. ex ledeb.)
      in the south of the Russian far east].
AB  - Allozyme variation of Japanese emperor oak Quercus dentata Thunb. and Mongolian
      oak Quercus mongolica Fisch. ex Lebed.) was examined in 11 populations of these
      species from southern Primorye. Analysis of 18 loci showed that in these
      populations, 66.7% of genes of Mongolian oak are polymorphic, the number of
      alleles per locus being 2.28. In Japanese emperor oak, these parameters were
      respectively 59.8 and 2.36%. The observed heterozygosity in both species did not
      differ from the expected values, constituting 0.198 in Japanese emperor oak and
      0.161 in Maongolian oak. The Nei's distance between Quercus mongolica and Q.
      dentate was 0.053. The Japanese emperor oak and Mongolian oak populations formed
      separate clusters in an UPGMA dendrogram. Taking into account morphological and
      ecological isolation of the species, we suggest that the differences in gene
      frequencies may reflect selection acting in favor of adaptation to different
      growth conditions and counteracting between-species hybridization.

PMID- 17555126
TI  - [Estimation of the efficiency of seed irradiation by thermal neutrons for
      inducing chromosomal aberrations in M1 of cotton Gossypium hirsutum l].
AB  - Exposure of cotton seeds to thermal neutrons at doses of 15, 25, and 35 Gy was
      shown to induce many altered plants, including sterile and chimeric ones. Most of
      these phenotypic changes were shown to result from novel genomic, chromosomal,
      and desynaptic mutations. The presence of these mutations in the karyotype of M,
      plants often decreased meiotic index and pollen fertility. In translocation
      forms, the decrease in pollen fertility was caused by the prevalence of
      quadrivalents in form of rings and chains with adjacent segregation of
      chromosomes from the translocation complexes. Based on the shapes and sizes of
      multivalent associations, we performed preliminary localization of translocation
      breakpoints. A specific feature of the effect of thermal neuron irradiation in M1
      was induction of numerous unique chromosomal aberrations, consisting in the
      appearance in the same plant of several types of mutations (genomic and
      chromosomal), exchange complexes in the same nucleus, and multiple exchanges
      involving three nonhomologous chromosomes.

PMID- 17555127
TI  - [Species-specific features of the protein patterns of diploid cotton seeds with A
      and D genomes and of some amphidiploids].
AB  - Differences between species were revealed in electrophoretic patterns of seed
      proteins of various diploid cotton species with A and D genomes and some
      amphidiploids. Reference spectra and electrophoretic formulas were compiled for
      representatives of diploid and amphidiploid species, and the electrophoretic
      spectra were visually evaluated. They would allow identification of various
      cotton species, varieties, and lines. Homology between cotton species was
      estimated from the results of electrophoretic protein studies. The homology
      between species of a single genome group was shown to be closer than between
      species belonging to different genome groups.

PMID- 17555128
TI  - Estimation of genetic diversity Among Turkish kale populations (Brassica oleracea
      var. acephala L.) using RAPD markers.
AB  - 20 populations of kale (B. oleracea var. acephala L.) selected from 127
      populations for fresh consumption terms of yield and leaf quality characteristics
      as superior types using weight-based ranking method from the Black Sea Region of
      Turkey were evaluated at the DNA level using randomly amplified polymorphic DNA
      (RAPD) markers compared to some morphological characters. The 7 primers selected
      from 100 decamers used generated 110 bands, of which 60 (54.5%) were polymorphic.
      Jaccard's genetic distances were calculated and dendogram was generated using the
      UPGMA algorithm. The dendogram obtained were classified into three main groups
      and four subgroups. The accessions showed a limited clustering in compare to
      morphological characters such as the number of leaf, leaf intentation of the
      margin, leaf and midrib color and thickness of midrib than geographical
      characteristics. Leaf color and midrib thickness characters clustered in the same
      group as OR49 and G18 accessions; S20, G6 and OR37 accessions, respectively.

PMID- 17555129
TI  - [Sex-linked erythrocyte antigens of the domestic pig].
AB  - It has been demonstrated that the domestic pig has a blood group systems whose
      haplotypes (complex alleles) are formed by at least three closely linked loci
      that are located, like the MIC2 locus of human blood group systems, in the
      homologous region of sex chromosomes.

PMID- 17555130
TI  - [Genetic structure of the sable Martes zibellina L. populations from magadan
      oblast as inferred from mitochondrial DNA variation].
AB  - Restriction polymorphism of the mtDNA cytochrome b gene was studied in nine sable
      Martes zibellina L. populations from three introduction foci of Khabarovsk and
      Kamchatka sables in Magadan oblast: Olya, Kolyma, and Omolon. For comparison,
      similar studies were performed with the populations of central Kamchatka and
      Khabarovsk krai. In total, 444 DNA specimens were examined. Three mtDNA
      haplotypes (A, B, and C) proved to occur at various frequencies in the
      populations under study. The sable population system displayed high
      differentiation (FST = 22.3%). The populations of the Olya focus were most
      similar genetically to the populations of Kamchatka; those of the Omolon focus
      were similar to the Khabarovsk populations, and those of the Kolyma focus
      occupied an intermediate place. The observed spatial heterogeneity of the sable
      populations of Magadan oblast was explained in terms of the formation of the
      introduction foci of Kamchatka and Khabarovsk sables, starting from the 1950s.

PMID- 17555131
TI  - [Mismatch repair (MMR) efficiency and MSH2 gene mutation in human colorectal
      carcinoma cell line COLO320HSR].
AB  - Colorectal cancer (CC) is one of two diseases, in which the link between cancer
      proneness and DNA repair deficiency appears to be proved. A strict relationship
      between mismatch repair (MMR) gene mutations, microsatellite instability (MSI)
      has been found in familiar colorectal cancer (Lynch syndrome). Tumorigenesis at
      familiar cancer is initiated by biallelic mutations in the major MMR genes,
      namely MSH2 or MLH1. One of these mutations is an inherited germline alteration
      and the other is a somatic one. The initiating mutation in sporadic colorectal
      tumors was not still identified although biochemical and genetic signs of MMR
      deficiency are observed in tumor cells. Two currently used colorectal tumor cell
      lines HCT116 and COLO320HSR were derived from hereditary and sporadic tumors
      accordingly. HCT116 cell line exhibits MMR-deficiency due to biallelic deletion
      in MLHL. As a consequence this shows MSI phenotype and a near-diploid karyotype.
      COLO320HSR cell line is characterized by MSS phenotype with mostly imbalanced
      aberrations. This indicates MMR proficiency in these cells. However, both MMR
      deficient HCT116 and COLO320HSR cells reveal near-diploid karyotype. Earlier we
      have shown that the number of secondary DNA double strand breaks, induced by
      methylnitrosourea (MNU), represent functional activity of cellular MMR. In the
      present study, using this approach we evaluated sensitivity to MNU and MMR
      activity in two colorectal tumor cell lines (HCT 116, COLO320HSR) and compared
      them to that in the HeLa cell line, which have MMR-proficient phenotype. We
      showed that cell line COLO320HSR exhibits low MMR activity, close to the level of
      MMR-activity in HCT116 cell line. We found a mutation in MSH2-G520A gene in
      COLO320HSR. This neutral mutation apparently is not related to polymorphism as we
      failed to identify the same mutation in any of MSH2 gene sequences of lymphocytes
      from 30 patients with sporadic colorectal cancer.

PMID- 17555132
TI  - Cytogenetic study of recurrent miscarriages and their parents.
AB  - There are substantial evidences that genetic alterations are contributing factors
      to the risk for recurrent miscarriages. This study was conducted to determine the
      frequency and contribution of chromosomal abnormalities in miscarriages and in
      couples with recurrent miscarriages. We studied a total of 41 miscarriages and
      their parents with a history of 2-11 recurrent miscarriages. Chromosomal analysis
      from chorionic villus sampling (CVS) and fetal tissues were performed according
      to standard cytogenetic methods using G-banding technique. Major chromosomal
      aberrations and polymorphic variants were found in 51 and 4.8%, respectively. The
      chromosomal abnormalities were structural (34.4%) and numerical (65.1%) of which
      26.1, 21.7, 8.7 and 8.7% were fetal sex aneuploid, triploid, mosaics and
      trisomic, respectively. Unbalanced and balanced rearrangements were found in
      17.2% and 8.6% of all abnormalities, respectively. Major chromosomal
      abnormalities in couples were seen in 4.9%. The chromosomal abnormalities
      associated with pregnancy losses and recurrent miscarriages are mostly numerical
      ones. The incidence of balanced translocations found here is 4.9% which is near
      to the mode (about 3-6%) observed in the previous studies. Those frequencies are
      greater than in the general population (0.3%). This indicates that balanced
      translocations, seen in parents, have some importance in causing miscarriage. The
      major parental chromosomal aberrations are significantly associated with fetal
      wastage. Mosaicism should be taken into account for cytogenetic analyses of
      pregnancy losses. Thus, cytogenetic analyses should be recommended in couples
      with recurrent miscarriages, when clinical data fail to clarify the cause.

PMID- 17555133
TI  - SNPs of PSMA6 gene--investigation of possible association with myocardial
      infarction and type 2 diabetes mellitus.
AB  - In our preceding studies we have identified microsatellite polymorphisms inside
      the PSMA6 gene and in its 5' upstream region. Following the observed associations
      of microsatellite polymorphisms with non-insulin dependent diabetes mellitus and
      Graves' disease we extended the evaluation of PSMA6 genetic variations to
      cardiovascular disorders and non-insulin dependent diabetes mellitus. New
      polymorphisms in the promoter region and exon 6 of the gene were identified by
      direct sequencing of the promoter region and all seven exons of the gene in 30
      individuals of European descent. Two SNPs at positions -110 and -8 from the
      translation start, in the promoter region and 5'UTR respectively, were analyzed.
      Neither polymorphism was associated with the risk of myocardial infarction. No
      significant association of the polymorphisms with plasma lipid levels or BMI was
      observed. A borderline association of both polymorphisms with diastolic blood
      pressure was observed in the control group. Genotype -8CG was significantly more
      frequent in type 2 diabetes patients, and haplotype C-110/G-8, compared to C
      110/C-8 was associated with a higher risk of NIDDM.

PMID- 17555134
TI  - [Analysis of the AluI polymorphism in intron 1 of the human coagulation factor
      VIII gene: a new marker for the hemophilia A carrier detection].
AB  - Frequencies of the CIT SNP alleles at position 2403 of the human coagulation
      factor VIII gene intron 1, containing the AluI restriction endonuclease
      recognition site, were examined. Genomic DNA samples for the analysis were
      obtained from the consulted women and their relatives from the families with
      hemophilia A. A total of 221 unrelated X chromosomes were studied. The two
      allelic variants were found with similar frequencies of T(Alu+), 0.53 and C(Alu
      ), 0.47. The heterozygosity index evaluated as equal to 0.50 was correlated with
      the experimental heterozygote number. The absence of a tight linkage between the
      AluI SNP and the widely used in the hemophilia A gene diagnostics HindIII
      polymorphism (CIT SNP at position 103 of intron 19) was demonstrated. Summarized
      informativity of these two markers for obligate carriers and for those detected
      in this study constituted 68% (32 out of 47). At the same time using one of the
      markers, only 40% (HindIII) and 51% (AluI) of the consulted women were
      informative. The new marker was used in 13 prenatal DNA diagnostics of hemophilia
      A. A new deletion polymorphism (del TGA, position 2281-2283 of intron 1) was
      described in close proximity of the AluI SNP with the frequency of about 0.05.
      among the five other SNP of the factor VIII gene examined (Bme 18I, intron 1;
      HpaII, intron 13; MnlI, exon 14; Bst4CI, exon 25; and MseI, exon 26) no effective
      diagnostic markers were found. Only the MnlI polymorphism could be recommended
      for limited usage.

PMID- 17555135
TI  - [The mechanisms of variation of subtelomeric repeats Speltl in the progeny of
      introgressive line Triticum aestivum L. x Aegilops speltoides Tausch].
AB  - Quantitative variation of species-specific subtelomeric repeat Speltl was studied
      in the progeny of an individual accession from the introgressive line Triticum
      aestivum x Aegilops speltoides. In the progeny, no cases of the Speltl increased
      content were observed. On the contrary, in some cases statistically significant
      decrease of the repeat copy number was detected. It seems likely that the
      mechanisms of the Spelt1 elimination involve either the selection at the gamete
      level versus the increase of the satellite DNA content in the telomeres, or
      intramolecular (within one chromatid) homologous recombination.

PMID- 17555136
TI  - [Studying recombination in heterozygous tandem duplications in Escherichia coli].
AB  - Our previous data showed that the principal pathway of the formation of selected
      recombinants in Escherichia coli strains carrying heterozygous tandem
      duplications is unequal crossing over between sister chromosomes. Data presented
      in this work showed that when DNA homology is not disturbed (due to transposon
      insertion), intragenic recombinants can occur directly in the region of
      recombination through intrachromomal exchange as well.

PMID- 17555137
TI  - Medicine and the pharmaceutical industry: a call to action.

PMID- 17555138
TI  - Management options for uterine fibroid tumors.

PMID- 17555139
TI  - U.S. statin guidelines: expensive but not necessarily effective.

PMID- 17555140
TI  - The importance of touch.

PMID- 17555141
TI  - Drug dosing adjustments in patients with chronic kidney disease.
AB  - Chronic kidney disease affects renal drug elimination and other pharmacokinetic
      processes involved in drug disposition (e.g., absorption, drug distribution,
      nonrenal clearance [metabolism]). Drug dosing errors are common in patients with
      renal impairment and can cause adverse effects and poor outcomes. Dosages of
      drugs cleared renally should be adjusted according to creatinine clearance or
      glomerular filtration rate and should be calculated using online or electronic
      calculators. Recommended methods for maintenance dosing adjustments are dose
      reductions, lengthening the dosing interval, or both. Physicians should be
      familiar with commonly used medications that require dosage adjustments.
      Resources are available to assist in dosing decisions for patients with chronic
      kidney disease.

PMID- 17555142
TI  - Uterine fibroid tumors: diagnosis and treatment.
AB  - The incidence of uterine fibroid tumors increases as women grow older, and they
      may occur in more than 30 percent of women 40 to 60 years of age. Risk factors
      include nulliparity, obesity, family history, black race, and hypertension. Many
      tumors are asymptomatic and may be diagnosed incidentally. Although a causal
      relationship has not been established, fibroid tumors are associated with
      menorrhagia, pelvic pain, pelvic or urinary obstructive symptoms, infertility,
      and pregnancy loss. Transvaginal ultrasonography, magnetic resonance imaging,
      sonohysterography, and hysteroscopy are available to evaluate the size and
      position of tumors. Ultrasonography should be used initially because it is the
      least invasive and most cost-effective investigation. Treatment options include
      hysterectomy, myomectomy, uterine artery embolization, myolysis, and medical
      therapy. Treatment must be individualized based on such considerations as the
      presence and severity of symptoms, the patient's desire for definitive treatment,
      the desire to preserve childbearing capacity, the importance of uterine
      preservation, infertility related to uterine cavity distortions, and previous
      pregnancy complications related to fibroid tumors.

PMID- 17555143
TI  - Acute pancreatitis: diagnosis, prognosis, and treatment.
AB  - Mild acute pancreatitis has a low mortality rate, but patients with severe acute
      pancreatitis are more likely to develop complications and have a much higher
      death rate. Although serum amylase and lipase levels remain the most widely used
      diagnostic assays for acute pancreatitis, other biomarkers and inflammatory
      mediators such as trypsinogens are being investigated for clinical use. Ranson's
      criteria, the Imrie scoring system, the Acute Physiology and Chronic Health
      Evaluation (APACHE II) scale, and the Computed Tomography Severity Index are
      systems for classifying severity of this disease; the Atlanta classification is
      widely used to compare these systems and standardize clinical trials. New
      developments in imaging modalities such as endoscopic ultrasonography and
      magnetic resonance cholangiopancreatography increase the options available to
      physicians for determining the cause of pancreatitis and assessing for
      complications. Enteral nutrition is preferred to parental nutrition for improving
      patient outcomes. Clinical trials are ongoing to evaluate the role, selection,
      and timing of antibiotics in patients with infected necrosis.

PMID- 17555144
TI  - Cerumen impaction.
AB  - Cerumen is a naturally occurring, normally extruded product of the external
      auditory canal. It is usually asymptomatic, but when it becomes impacted it can
      cause complications such as hearing loss, pain, or dizziness. It also can
      interfere with examination of the tympanic membrane. Depending on available
      equipment, physician skill, and patient circumstances, treatment options for
      cerumen impaction include watchful waiting, manual removal, the use of
      ceruminolytic agents, and irrigation with or without ceruminolytic pretreatment.
      The overall quality of the evidence on treatment is limited. Referral to an
      otolaryngologist for further evaluation is indicated if treatment with a
      ceruminolytic agent followed by irrigation is ineffective, if manual removal is
      not possible, if the patient develops severe pain or has vertigo during
      irrigation, or if hearing loss is still present after cerumen has been removed.
      The use of cotton swabs and ear candles should be avoided.

PMID- 17555145
TI  - Information from your family doctor. Earwax: what you should know.

PMID- 17555146
TI  - Predicting postoperative nausea and vomiting.

PMID- 17555147
TI  - Pain in the right lower quadrant.

PMID- 17555149
TI  - The wavering flame: professional burnout.

PMID- 17555148
TI  - Effective care.

PMID- 17555150
TI  - Palliative care teams on the prairie: composition, perceived challenges &
      opportunities.
AB  - INTRODUCTION: LifeCircle South Dakota: Partners Improving End-of-Life Care is an
      interdisciplinary group committed to quality end-of-life care for residents of
      the state. Strengthening local coalitions and building a collaborative network
      among palliative care providers were goals of recent educational efforts. This
      article presents a profile of South Dakota palliative care teams. METHODS: South
      Dakota health care facilities and key professionals in palliative and hospice
      care (n=786) were invited to attend a palliative care conference in the summer of
      2006. Forty-nine teams of two or more persons registered for the conference, and
      40 teams completed surveys. The questionnaires asked how palliative care is
      delivered in a rural state, where teams go for help and consultation, and what
      teams perceive as the challenges and opportunities facing interdisciplinary
      teams. Both qualitative and quantitative data from the purposive sample of 40
      South Dakota palliative care teams were analyzed. RESULTS: Thirty-five teams
      (88%) indicated nursing was included on their teams while only six (15%) included
      physicians. Twenty-five teams (62%) desired to add chaplaincy to their teams,
      followed by pharmacy (25/60%) and medicine (22/55%). On average, 42% of the
      primary team member's time was devoted to palliative care. Pain management, other
      symptom management, spiritual issues, advance directives, and family support were
      identified as critically important to practice. Teams consulted physicians for
      pain and non-pain symptom management, but sought hospices and team colleagues for
      consultation on advance directive, family, and spiritual issues. The top
      challenge teams identified in delivering end-of-life care was short length of
      hospice stay (lateness or lack of referral to hospice). CONCLUSIONS: Survey data
      generated a profile of palliative care teams in the state-their composition, self
      reported levels of palliative care expertise, resources utilized for
      consultation, and perceived challenges and opportunities facing them in providing
      end-of-life care. Having this understanding, along with knowing the perceived
      challenges and opportunities these teams face, will strengthen our ability to
      further enhance end-of-life care for South Dakotans.

PMID- 17555152
TI  - Comparison of various phytonadione (vitamin K1) administration routes in
      achieving warfarin reversal.

PMID- 17555151
TI  - Beyond borders: cultural competence education for medical students.

PMID- 17555153
TI  - DAKOTACARE introduces its second Medicare program.

PMID- 17555154
TI  - The physician's role in reducing avoidable hospitalizations.

PMID- 17555155
TI  - Nurses realize the full potential of technology.

PMID- 17555156
TI  - Increasing access to cardiac rehabilitation through telemedicine technology.

PMID- 17555157
TI  - CNA moves forward on e-nursing strategy.

PMID- 17555159
TI  - CNA brings voice of Canadian nurses to international conference.

PMID- 17555158
TI  - CNA and ASI pilot state-of-the-art testing technology.

PMID- 17555160
TI  - The state of nursing informatics in Canada.

PMID- 17555161
TI  - Telenursing in hospice palliative care.
AB  - During the last months of life, many people with advanced illness will be living
      in their homes. Coping with changing symptoms, and ultimately preparing for
      death, becomes part of daily life. Whether the ill person is at home for days or
      for months, they depend on family or friends to be primary caregivers, supported
      by home-based services. However, after physician and home health offices close,
      many patients and their caregivers are left to cope alone. The authors describe
      an innovative partnership between B.C. NurseLine (a provincial tele-triage and
      health information call centre), the British Columbia Ministry of Health and
      Fraser Health Hospice Palliative Care program that created after-hours access to
      care for dying patients and their families in one of Canada's largest health
      authorities. The article outlines how information and communications technology
      enabled merging the capacity and expertise of B.C. NurseLine with the expertise
      of specialized community-based palliative care services to achieve outcomes of
      improved symptom management, decreased visits to emergency rooms and enhanced
      support for families who are caring for loved ones at home. For nurses caring for
      home-based patients, there are lessons to be learned about how to maximize
      technology to create systems that both improve access to care and are sustainable
      in the future.

PMID- 17555162
TI  - Computerized Client assessments: a change in practice.
AB  - Inconsistencies in home and community care data collection across Canada was the
      driving force for changing the process of assessment of case-managed clients in
      British Columbia. Clinicians had been using a paper-based assessment tool but
      were mandated to implement the RAI-HC and to conduct assessments using a
      computerized version. This led to a significant change in clinical practice. The
      authors provide an overview of the transition in the Interior Health Authority,
      linking phases of the process to Kotter's model of creating major change.

PMID- 17555163
TI  - Blending technology and practice. Interview with Gail J Donner and Mary M.
      Wheeler.

PMID- 17555164
TI  - Embracing information technology--a two-way street.

PMID- 17555165
TI  - CT--how many ways should you slice it? Why 64 slices may be more than you need.

PMID- 17555166
TI  - GE healthcare Logiq i portable ultrasound scanner.

PMID- 17555167
TI  - CT scans can affect the operation of implanted electronic devices.

PMID- 17555168
TI  - Switch failure on Siemens Aristos FX x-ray tube support may lead to uncontrolled
      system movement.

PMID- 17555169
TI  - Art and science.

PMID- 17555170
TI  - A clinical study on interdental separation techniques.
AB  - The effect of interdental separation of a special separation ring and wooden
      wedge was investigated. In a split-mouth design, 27 patients were randomly
      assigned to one of two groups (W or S). In 11 patients, an interdental wooden
      wedge (Hawe-Neos) was placed (group W), and in 16 patients, a separation ring
      (Composi-Tight Gold) was placed at the contact between teeth 4/5 and 5/6.
      Simultaneously, in both groups, a wooden wedge, combined with a separation ring
      (Composi-Tight Gold), was placed on the contact between teeth 4/5 and 5/6
      (reference group W+S). To measure proximal contact tightness, frictional forces
      were recorded at the removal of a 0.05 mm thick metal matrix band inserted
      between adjacent teeth. Contact tightness was measured at contacts 4 and 5 and at
      5 and 6 in the third and fourth quadrant using the Tooth Pressure Meter prior to
      applying separation devices (TO) five minutes after application (T1) and five
      minutes after removal of the devices (T2). The effect of separation was
      determined by calculating the differences between contact tightness before
      application and contact tightness with the devices in situ (T1-T0). Interdental
      recovery was calculated by the difference in contact tightness before application
      and after removal of the devices (T2-T0). To assess the presence of statistically
      significant differences between these measurement times, paired t-tests were
      applied. With each patient, either a comparison between W and W+S or S and W+S
      was made. For both W versus W+S and S versus W+S, paired t-tests were applied to
      compare differences (T1-T0 and T2-T0) between the separation devices. Within a
      patient, groups W and S could not be compared, therefore, to compare separation
      achieved between these two devices, unpaired t-tests were used. The increase in
      contact tightness measured at contact 4 and 5 for group W (0.98 +/- 0.26 N) was
      statistically significantly less compared to the increase in group S (5.48 +/-
      0.88 N) (p < 0.001) or group W+S (4.62 +/- 0.68 N) (p = 0.02). No significant
      differences were found between groups S and W+S (p = 0.77). For all groups, five
      minutes after removal of the devices, the contact tightness at contact 4 and 5
      and at contact 5 and 6 were still significantly weaker compared to the tightness
      at baseline (p < 0.02). When separation is required for restorative procedures,
      such as at placement of a Class II resin composite restoration, special
      separation rings may be more useful than wooden wedges.

PMID- 17555171
TI  - Effect of restoration size on the clinical performance of posterior "packable"
      resin composites over 18 months.
AB  - Fifty predominantly moderate or large Class II or multiple-surface Class I resin
      composite restorations were placed in molars under rubber dam isolation. The
      restorative systems used were: Alert Condensable (Jeneric/Pentron) and SureFil
      (Dentsply/Caulk). The restorations were classified according to size, with 7
      small, 25 moderate and 18 large, of which 8 were cusp replacement restorations.
      Baseline, 6, 12 and 18-month double-blinded clinical evaluations were carried out
      using modified USPHS criteria. The independent variables: restorative material,
      restoration size and three other clinical factors, were tested using a Multiple
      Logistic Regression procedure to determine if any were predictive of failure. Of
      the 50 restorations, four failed by the 18-month recall, three failed due to
      fracture of the restoration and one due to secondary caries. Both restorative
      systems demonstrated a 92% success rate. No association between restoration size
      (p = 0.99) or restorative material (p = 0.65) and failure was found. Similarly,
      the additional variables, occlusal contact type, presence of occlusal wear facets
      and first or second molar, were not predictive of failure.

PMID- 17555172
TI  - Influence of air abrasion and long-term storage on the bond strength of self
      etching adhesives to dentin.
AB  - This study tested the effects of long-term storage and aluminum oxide air
      abrasion on the bond strength of self-etching adhesive systems. Extracted human
      third molars were ground flat with 600-grit SiC paper to expose middle coronal
      dentin. Clearfil SE Bond and One-Up Bond F were applied to dentin surfaces in
      accordance with manufacturers instructions with or without previous aluminum
      oxide 50 microm air abrasion. A crown was built up with the resin composite TPH
      Spectrum and the specimens were stored in water for 24 hours. The bonded
      assemblies were vertically sectioned into beams for microtensile bond testing.
      The beams of each tooth were individually immersed in bottles containing water at
      37 degrees C for one day, three and six months; the water was changed daily. The
      specimens were then subjected to microtensile bond testing. The bond strength
      data were subjected to ANOVA and Tukey Kramer test. Fractured specimens were
      analyzed in a scanning electron microscope to determine failure modes. Air
      abrasion improved Clearfil SE Bond bond strength in the three month evaluation.
      No significant difference was found between the two adhesives systems, but bond
      strengths gradually decreased over time. Failure modes varied significantly among
      groups and were influenced by long-term storage and aluminum oxide air abrasion.

PMID- 17555173
TI  - Detection and activity assessment of primary coronal caries lesions: a
      methodologic study.
AB  - This study has three main objectives: Study (1) test the reproducibility and
      accuracy of the ICDAS I and ICDAS II caries detection systems; Study (2) validate
      a new impression material (Clinpro, 3M ESPE), which is said to detect lactic acid
      in plaque fermenting sucrose; Study (3) devise and test a scoring system for the
      assessment of caries activity of coronal lesions. Study (1): 141 extracted teeth
      were examined by two examiners using the ICDAS I and ICDAS II caries detection
      systems and validated against a histological classification system. Study (2):
      The accuracy of the impression material in predicting plaque with pH lower/higher
      than 5.5 was determined in an in situ study of 45 root dentin specimens by
      comparing the color change in the impression with the actual pH of the plaque,
      determined with a pH meter. Study (3): A scoring system to assess lesion activity
      was devised based on the predictive power of the visual appearance of the lesion
      (ICDAS II system), location of the lesion in a plaque stagnation area and,
      finally, the tactile feeling, rough/soft or smooth/hard, when running a perio
      probe over the lesion. The accuracy was tested in a clinical study of 35 children
      with 225 lesions/sound surfaces and was validated using the Clinpro impression
      material for construct validity. Study (1): Intra- and inter-examiner
      reproducibility was found to be excellent (Kappa-values > 0.82) and the
      associations strong (Spearmans correlation coefficients > 0.90). Study (2): The
      Clinpro impression material was found to be acceptable as compared to the results
      of a pH meter, the combined sensitivity and specificity was 1.63. Study (3): ROC
      analysis showed that the devised classification system for determining lesion
      activity had acceptable accuracy (area under curve = 0.84 and the highest
      combined sum of specificity and sensitivity was 1.67). Thus, it is possible to
      predict lesion depth and assess the activity of primary coronal caries lesions
      accurately by using the combined knowledge obtained from visual appearance,
      location of the lesion and tactile sensation during probing.

PMID- 17555174
TI  - Quantity of remaining bacteria and cavity size after excavation with FACE, caries
      detector dye and conventional excavation in vitro.
AB  - In this in vitro study, quantitative confocal microscopy was used to show
      differences in the quantity of bacteria remaining in dentin after excavation with
      different methods. A further parameter was the cavity volume after excavation
      relative to the original lesion size. Teeth with dentin caries were divided into
      three groups of 20 each. The caries was removed by a single operator using a slow
      handpiece and a round bur. In the first group, Fluorescence Aided Caries
      Excavation (FACE) was carried out: violet light was used to illuminate the
      operating field and the operator observed the cavity through a high-pass filter
      and removed the orange-red fluorescing areas. The second group was excavated
      using Caries Detector, while the third group used conventional excavation. After
      excavation, cavity volume was measured; samples were stained for bacteria with
      ethidium bromide, and they were examined using confocal microscopy under
      standardized conditions. The bound stain was quantified in terms of fluorescence
      intensity on the confocal images. Total pixel intensity was significantly lower
      in the FACE Group than in the Caries Detector group (p = 0.046) and in the
      conventional excavation group (p = 0.021). Differences in cavity volume relative
      to original lesion size were not statistically significant (p = 0.86, 0.35 and
      0.51). Within the limitations of this in vitro study, it can be concluded that
      FACE is more effective in removing infected dentin without significantly
      increasing cavity size when compared to conventional excavation and excavation
      with the aid of caries detector dye.

PMID- 17555175
TI  - Effect of pulp pressure on the micropermeability and sealing ability of etch &
      rinse and self-etching adhesives.
AB  - This research evaluated the effect of pulp pressure on the micropermeability and
      sealing ability of etch & rinse and self-etching adhesives. Two etch & rinse
      adhesives (Prime&Bond NT and Admira Bond) and one self-etching adhesive (Xeno
      III) were used. Adhesive layer micropermeability was evaluated by using confocal
      laser scanning microscopy (CLSM). Eighteen molars were connected to a pulp
      pressure device and divided into two groups. One group was restored with pulp
      pressure and the other group without. Each group was divided into three subgroups
      according to the adhesive used. The adhesives were rhodamine-labeled and Class V
      cavities were restored. After restoration, all specimens were kept under pulp
      pressure conditions for 24 hours with fluorescein-labeled pulp fluid. The
      specimens were sectioned and the axial wall was observed under CLSM. A
      microleakage test was performed to evaluate the sealing. Thirty molars were
      divided into two groups. One group was prepared with a pulp pressure device and
      the other group without. Each group was divided into three subgroups as a
      function of the adhesive used. Class V cavities were restored and the specimens
      were immersed in fuchsin and sectioned. Microleakage and dentin penetration were
      recorded in the occlusal and gingival walls. A CLSM study showed that the etch &
      rinse adhesives had higher micropermeability compared to the self-etching
      adhesives and pulp pressure made all the adhesives more permeable. In the
      occlusal wall, the best sealing (hermetic) was obtained when etch & rinse
      adhesives were used. Xeno obtained the lowest occlusal sealing values. In the
      gingival wall, Xeno obtained the best sealing, followed by Admira and Prime&Bond.
      Pulp fluid decreased gingival wall sealing when etch & rinse adhesives were used
      but not when self-etching adhesive was used.

PMID- 17555176
TI  - Partial ceramic crowns: influence of ceramic thickness, preparation design and
      luting material on fracture resistance and marginal integrity in vitro.
AB  - This in vitro study tested the effects of two different ceramic thicknesses, two
      preparation designs and two different luting agents on the marginal integrity and
      fracture resistance of partial ceramic crowns (PCC). Eighty extracted human
      molars were prepared according to the following preparation designs: a) Coverage
      of functional cusps/butt joint (n=40), b) Horizontal reduction of functional
      cusps (n=40). PCC (Vita Mark II, Cerec3 System) were fabricated and the ceramic
      thickness of the functional cusps was adjusted to (1): 0.5-1.0 mm and (2): 1.5
      2.0 mm. PCC were adhesively luted to the cavities with either Excite/VariolinkII
      (VL) or RelyX Unicem (RX). The specimens were exposed to thermocycling and
      central mechanical loading (5000 x 5 degrees C-55 degrees C; 30 second/cycle;
      50,0000 x 72.5N, 1.6Hz). Marginal integrity was assessed by evaluating dye
      penetration (fuchsine) on multiple sections in the bucco-oral direction by
      relating the actual penetration distance to the maximal length of the
      corresponding cavity wall (100%). Restoration/luting agent (RL)--and tooth/luting
      agent (TL) interfaces were evaluated separately. The data were statistically
      analyzed with the Mann Whitney U-test and the Error Rates Method (ERM), and the
      fracture rates were analyzed with the chi2-test. Dye penetration data indicated
      that ceramic thickness and luting agent had a statistically significant influence
      upon marginal integrity in general, irrespective of all other parameters (ERM):
      RX showed significantly lower microleakage along the RL interface than VL. VL
      revealed significantly lower microleakage at the TL interface than RX. Fifteen
      PCC of group 1 (0.5-1.0 mm) and two PCC of group 2 (1.5-2.0 mm) were fractured
      after thermocycling and central mechanical loading, with the difference being
      statistically significant. PCC fabricated from industrially sintered feldspathic
      ceramic should have at least a thickness of 1.5-2.0 mm in stress-bearing areas.

PMID- 17555177
TI  - The importance of dentin collagen fibrils on the marginal sealing of adhesive
      restorations.
AB  - This study evaluated the importance of the union between dentin collagen and
      three different adhesive materials. Sixty Class V restorations were prepared on
      the buccal and lingual surfaces of 30 recently extracted human premolars, with
      the cervical margins in dentin and the occlusal margins in enamel. These
      restorations were distributed to three groups of 20 cavities each based on the
      employed adhesive system used: Group A: Single Bond; Group B: Prime&Bond NT;
      Group C: One Coat Bond. Each group was subdivided according to dentin treatment:
      (1) manufacturers' adhesive protocol and (2) removal of the collagens fibers
      (total etch + sodium hypochlorite 5% for two minutes) + adhesive protocol. After
      the restorations were completed, the teeth were stored in saline solution (24
      hours/37 degrees C), subjected to thermal cycling, washing and scoring according
      to dye penetration. Dye penetration was evaluated, with the numbers ranging from
      0 (no infiltration) to 3 (greatest infiltration). When the dentin microleakage
      scores were compared in subgroups A1XA2, B1XB2 and C1XC2, the Mann-Whitney Test
      revealed significant differences between groups B and C (p < 5%). The better
      results were shown in subgroups B2 (p = 0.0345) and C2 (p = 0.0029). The results
      showed that the collagen fibrils were not necessary for adhesion, and their
      removal positively influenced the marginal sealing of Prime&Bond NT and One Coat
      Bond.

PMID- 17555178
TI  - Visualization of marginal integrity of resin-enamel interface by holographic
      interferometry.
AB  - This study determined whether it was possible to detect deformations and
      fractures in dental hard tissues or in composite material from internal stresses
      using double-exposure holographic interferometry. On the proximal side of eight
      intact human permanent premolars, a direct Class II cavity was prepared and
      restored with a self-etching adhesive (Clearfil SE Bond) and Tetric Ceram, a
      resin composite. In five of the specimens, Tetric Flow was used as an elastic
      layer. The samples were illuminated using a helium-neon laser beam, and the
      holograms of samples were recorded using Agfa 10E75 photographic plates. Hologram
      reconstructions were captured with an 8-bit monochrome CCD camera and
      qualitatively analyzed. Deformations and fractures appeared as fringe patterns on
      all interferograms, where the distribution of fringes provided location
      information, while the density of fringes gave the amplitude information. Greater
      fringe densities were observed in samples treated without a flowable composite.

PMID- 17555179
TI  - Effects of sonic and ultrasonic scaling on the surface roughness of tooth-colored
      restorative materials for cervical lesions.
AB  - This study investigated the effects of sonic and ultrasonic scaling on the
      surface roughness of five commonly used tooth-colored restorative materials for
      Class V cavities, including a flowable resin composite (Tetric Flow), a compomer
      (Compoglass F), a glass ionomer (Fuji II), a resin-modified glass ionomer (Fuji
      II LC Imp) and a resin composite (Z100). Twenty rectangular block specimens (16 x
      6 x 1.5 mm) of each material were cured against matrix strips, then stored in
      artificial saliva for two months before performing the periodontal
      instrumentation. Each specimen was divided into two experimental zones, and both
      scaling treatments were performed on each sample. The surface roughness (Ra) of
      these materials was determined before and after the different instrumentations,
      and differences were evaluated with the use of a profilometer. Data were
      statistically analyzed using repeated measures of ANOVA with Tukey's multiple
      comparisons and paired t-tests at a significance level of 0.05. Significant
      increases in surface roughness of all test materials were recorded from both
      scaling treatments. With the exception of Tetric Flow, ultrasonic scaling had
      more adverse effects on the surface roughness of all test materials compared to
      sonic scaling. For the test materials Z100 and Tetric Flow, resin composites
      showed the least surface changes in both scaling treatments, while Fuji II glass
      ionomer demonstrated the greatest roughness after instrumentation. More
      importantly, the mean surface roughness values of several materials after
      instrumentation were above the critical threshold roughness of 0.2 microm.

PMID- 17555180
TI  - Composite photopolymerization with diode laser.
AB  - Under clinical conditions, the time needed for the proper light curing of luting
      composites or the multi-incremental buildup of a large restoration with halogen
      curing units is quite extensive. Due to the development of high power curing
      devices, such as argon lasers and plasma arc lights and, in order to decrease
      curing time, halogen and LED devices have developed a high intensity
      polymerization mode. This study compared the degree of conversion using Fourier
      Transform Infrared Spectroscopy (FT-IR) of two composite materials: Tetric Ceram
      and Tetric EvoCeram polymerized with three polymerization modes (high, low and
      soft mode) of a Bluephase 16i LED curing unit and blue diode laser intensity of
      50 mW on the output of the laser beam and 35 mW/cm2 on the resin composite
      sample. Descriptive statistic, t-test, ANOVA, Pearson Correlation and Tukey Post
      hoc tests were used for statistical analyses. The results show a higher degree of
      conversion for the polymerization of composite samples with all
      photopolymerization modes of the LED curing unit. However, there is no
      significant difference in the degree of conversion between the LED unit and 50
      second polymerization with the blue diode laser. Tetric EvoCeram shows a lower
      degree of conversion regardless of the polymerization mode (or light source)
      used.

PMID- 17555181
TI  - The effect of marginal ridge thickness on the fracture resistance of
      endodontically-treated, composite restored maxillary premolars.
AB  - This study evaluated the effect of varying thicknesses of marginal ridge on the
      fracture resistance of endodontically-treated maxillary premolars restored with
      composite. Ninety non-carious maxillary premolars, extracted for orthodontic
      reasons, were selected for this experimental in vitro study. The teeth were
      randomly assigned to six groups (n=15). Group 1 received no preparation. In
      groups 2 through 6, the premolars were root filled and DO preparations were
      created, while MOD preparations were also created for group 2. The condition of
      the boxes was: the gingival seat was 1.5 mm above the CEJ and the buccolingual
      dimensions were 3.5 mm in gingival and 3 mm in occlusal. In groups 3 through 6,
      the dimensions of the mesial marginal ridge were measured using a digital caliper
      as follows: 2 mm, 1.5 mm, 1 mm and 0.5 mm, respectively. All samples in groups 2
      through 6 were restored with a dentin bonding system (DBS: Single Bond, 3M) and
      resin composite (Z 250, 3M). Subsequently, premolars from all six groups were
      subjected to a thermocycling regimen of 500 cycles between 5 degrees C and 55oC
      water baths. Dwell time was 30 seconds, with a 10-second transfer time between
      baths. The premolars were submitted to axial compression up to failure at a 45
      degrees angle to the palatal cusp in Universal Test Equipment (Tinius Olsen, Ltd,
      H5K-S model). The mean load necessary to fracture the samples was recorded in
      newtons (N), and data were subjected to analysis of variance (ANOVA) and LSD post
      hoc test. According to these results, the mean loads necessary to fracture the
      samples in each group were (in N): group 1: 732 +/- 239, group 2:489 +/- 149,
      group 3: 723 +/- 147, group 4: 696 +/- 118, group 5: 654 +/- 183 and group 6: 506
      +/- 192). Differences between group 1 and groups 2 and 6, and also differences
      between groups 3, 4 and 5 compared with group 2 and 6 were statistically
      significant (p < 0.05).

PMID- 17555182
TI  - Influence of beveling and ultrasound application on marginal adaptation of box
      only Class II (slot) resin composite restorations.
AB  - A laboratory study was performed to assess the influence of beveling the margins
      of cavities and the effects on marginal adaptation of the application of
      ultrasound during setting and initial light curing. After minimal access cavities
      had been prepared with an 80 microm diamond bur, 80 box-only Class II cavities
      were prepared mesially and distally in 40 extracted human molars using four
      different oscillating diamond coated instruments: (A) a U-shaped PCS insert as
      the non-beveled control (EMS), (B) Bevelshape (Intensiv), (C) SonicSys (KaVo) and
      (D) SuperPrep (KaVo). In groups B-D, the time taken for additional bevel
      finishing was measured. The cavities were filled with a hybrid composite material
      in three increments. Ultrasound was also applied to one cavity per tooth before
      and during initial light curing (10 seconds). The specimens were subjected to
      thermomechanical stress in a computer-controlled masticator device. Marginal
      quality was assessed by scanning electron microscopy and the results were
      compared statistically. The additional time required for finishing was B > D > C
      (p < or = 0.05). In all groups, thermomechanical loading resulted in a decrease
      in marginal quality. Beveling resulted in higher values for "continuous" margins
      compared with that of the unbeveled controls. The latter showed better marginal
      quality at the axial walls when ultrasound was used. Beveling seems essential for
      good marginal adaptation but requires more preparation time. The use of
      ultrasonic vibrations may improve the marginal quality of unbeveled fillings and
      warrants further investigation.

PMID- 17555183
TI  - Gingival microleakage of Class II resin composite restorations with fiber
      inserts.
AB  - PURPOSE: This investigation evaluated the effect of glass and polyethylene fiber
      inserts on the microleakage of Class II composite restorations with gingival
      margins on root surfaces. METHODS: Fifty-four intact molars were sterilized with
      Gamma irradiation and mounted in acrylic bases. Class II slot cavities were made
      on both proximal sides of each tooth (3 mm wide, 1.5 mm deep) with the gingival
      margin on the root surface. The teeth were divided into nine groups, according to
      the technique of restoration and type of bonding agent. Filtek P-60 (3M/ESPE) was
      used to restore all cavities. Two types of fiber inserts were used: glass fiber
      (Ever Stick, StickTech) and polyethylene (Ribbond-THM), with three bonding agents
      being employed: Scotch Bond Multipurpose (3M/ESPE), Clearfil SE Bond (Kuraray)
      and Xeno IV (Dentsply). In the experimental groups, 3 mm long fiber inserts were
      inserted into restorations at the gingival seat. The control groups had no fiber
      inserts. The restorations were made incrementally and cured with LED light
      (UltraLume5, Ultradent). The restored teeth were stored in water for two weeks,
      then thermocycled for 3000 cycles (5 degrees C and 55 degrees C). The tooth
      surfaces were sealed with nail polish, except at the restoration margins. The
      teeth were immersed in 2% procion red dye solution, sectioned and dye penetration
      was assessed to determine the extent of microleakage according to a six-point
      scale. RESULTS: The fiber groups generally showed reduced microleakage scores
      compared to the control groups. The Clearfil SE Bond (Kuraray)/Filtek P-60
      (3M/ESPE) combination produced the lowest degree of microleakage, irrespective of
      fiber type. However, the glass fiber groups were more consistent in reducing
      microleakage than the polyethylene groups. CONCLUSIONS: The use of fiber inserts
      significantly reduced gingival microleakage in Class II composite restorations
      with gingival margins in dentin, irrespective of the adhesive used. Clearfil SE
      Bond (Kuraray)/Filtek P60 (3M/ESPE) produced the lowest microleakage scores.

PMID- 17555184
TI  - Restoration of erosion associated with gastroesophageal reflux caused by anorexia
      nervosa using ceramic laminate veneers: a case report.

PMID- 17555185
TI  - Take 30 seconds to save a life.

PMID- 17555186
TI  - Praise for Smigel interview.

PMID- 17555187
TI  - Using digital photography to increase case acceptance in hygiene.

PMID- 17555188
TI  - Zirconium CAD/CAM and bioesthetic layering of porcelain: color from within.

PMID- 17555189
TI  - Using orthodontics to alter gingival levels.

PMID- 17555190
TI  - Digital smile enhancement: an essential modality for any successful cosmetic
      practice.

PMID- 17555191
TI  - The epidemic of cracked and fracturing teeth.

PMID- 17555192
TI  - Digital dental photo update 2007 with a bonus: advanced portraiture made simple.

PMID- 17555193
TI  - The vision of digital dental photography.
AB  - Digital dental photography has been crucial to the advancement of cosmetic dental
      procedures. It is an effective and necessary tool in the aesthetic dentist's
      armamentarium. Practice will allow the dentist to archive treatment results and
      allow every case to be improved. Dentists wishing to advance their techniques and
      to complete accreditation protocols should master these techniques.

PMID- 17555194
TI  - Same-day implants and prosthesis: case report.

PMID- 17555195
TI  - Hydrodynamic disinfection: tsunami endodontics.

PMID- 17555196
TI  - Integrating ultrasonic tips into the endodontic treatment armamentarium.
AB  - The integration of ultrasonic tips in conventional and surgical endodontic
      treatment can be useful for the clinician. An ultrasonic tip is used in
      conventional endodontic treatment to remove or bypass a separated instrument or a
      post within a canal, and can replace a slow-speed handpiece and round bur to
      detect or provide better access to a canal. In endodontic surgery, the
      replacement of the slow-speed or miniature handpiece with an ultrasonic tip will
      allow for better instrument ergonomics and depth of a root-end preparation. When
      used in conjunction with magnification and illumination, visualization for the
      clinician is markedly improved. In addition, advancements in polymer science have
      allowed for the development of plastic ultrasonic tips.

PMID- 17555198
TI  - Turning "problem patients" into "perfect patients".

PMID- 17555197
TI  - Methamphetamine abuse and the impact on dental health.

PMID- 17555199
TI  - Maximize clinical productivity and practice growth ... take action now! Part 1.

PMID- 17555200
TI  - Digital X-ray file sharing redefines the "solo" practitioner.

PMID- 17555201
TI  - Impact agricultural safety and health: know producers, know agriculture, and
      engage in a professional community of practice.

PMID- 17555202
TI  - Health risk behaviors and work injury among hispanic adolescents and farmworkers.
AB  - Adolescents may engage in health risk behaviors that increase their likelihood of
      injury. Employment places adolescents at risk of work-related injuries. This
      study responds to the paucity of data on the relationship between adolescent
      health risk behaviors and work-related injury. This cross-sectional study
      included the administration of anonymous surveys to ninth graders (n=4914) who
      attended high schools in south Texas. An aggregate risk score (ARS) was developed
      based on health risk behaviors. The ARS was analyzed as an outcome using linear
      regression. Associations between health risk behaviors and work-related injury
      were assessed with logistic regression. Of the respondents, 19% reported they had
      a job, and 14% reported that they had been employed in farmwork. Farmwork-related
      injury was reported by 9% of adolescents, and 12% reported other work-related
      injury. Mean ARS scores were significantly higher (p < 0.05) for both male and
      female adolescents who reported a work-related injury compared to nonworking
      adolescents, and for males who had done migrant farmwork compared to all other
      adolescent males. The ARS increased as hours worked per week increased. After
      controlling for confounding factors, a statistically significant association was
      found between ARS and non-farmwork, work-related injury, but not between ARS and
      farmwork-related injury. Farmworkers with high ARS were more likely to report non
      farmwork, work-related injuries. The predictors of work-related injury in the
      adolescent groups, particularly for farmworkers and migrants who are under
      additional stress, remain an important occupational health area to be addressed.

PMID- 17555203
TI  - Evaluation of engineering plastic for rollover protective structure (ROPS)
      mounting.
AB  - Agriculture has one of the highest fatality rates of any industry in America.
      Tractor rollovers are a significant contributor to the high death rate. Rollover
      protective structures (ROPS) have helped lower these high fatality rates on full
      size tractors. However, a large number of older tractors still do not use ROPS
      due to the difficulty of designing and creating a mounting structure. To help
      reduce this difficulty, engineering plastics were evaluated for use in a ROPS
      mounting structure on older tractors. The use of engineering plastics around axle
      housings could provide a uniform mounting configuration as well as lower costs
      for aftermarket ROPS. Various plastics were examined through shear testing, scale
      model testing, and compressive strength testing. Once a material was chosen based
      upon strength and cost, full-scale testing of the plastic's strength on axle
      housings was conducted. Finally, a mounting structure was tested in static ROPS
      tests, and field upset tests were performed in accordance with SAE Standard
      J2194. Initial tests revealed that the ROPS mounting structure and axle housing
      combination had higher torsional strength with less twisting than the axle
      housing alone. An engineering plastic ROPS mounting structure was easily
      successful in withstanding the forces applied during the static longitudinal and
      lateral ROPS tests. Field upset testing revealed that the mounting structure
      could withstand the impact loads seen during actual upsets without a failure.
      During both static testing and field upset testing, no permanent twisting of the
      mounting structure was found. Engineering plastic could therefore be a viable
      option for a universal ROPS mounting structure for older tractors.

PMID- 17555204
TI  - Analysis of 151 agricultural driveline-related incidents resulting in fatal and
      non-fatal injuries to U.S. children and adolescents under age 18 from 1970
      through 2004.
AB  - Agricultural driveline-related incidents have been identified as an important
      cause of farm-related injury resulting in death and permanently disabling
      conditions to children and adolescents. A database of driveline-related injuries,
      including both PTO drivelines and secondary shafts and drivelines on agricultural
      equipment, developed at Purdue University was mined to identify all cases
      involving children and adolescents under age 18 who had been involved in a
      driveline-related incident from 1970 through 2004. Although these incidents did
      not account for a high percentage of all childhood farm-related injuries, this
      age group was found to make up nearly one in four documented agricultural
      driveline incidents. Of the 685 cases in the database with known ages, 151 were
      identified as youth under age 18. Findings indicated that these incidents often
      resulted in catastrophic injuries including amputation, spinal cord injuries, and
      compound bone fractures. Over the period studied, the trend in documented cases
      is declining, with recent years reporting below the yearly average and 2004
      reporting no fatalities. Youth, primarily males, age 13 had the highest frequency
      of incidents, and over 50% of all cases occurred to youth ages 12 to 17. Fall was
      identified as the season with the most reported incidents. Amputations were
      documented in nearly 50% of all cases, and augers, elevators, and conveyors were
      the machines most frequently identified as being involved in the incident.
      Recommendations and strategies that specifically target the childhood injury
      problem related to agricultural drivelines are provided.

PMID- 17555205
TI  - Installing a cost-effective rollover protective structure (CROPS): a cost
      effectiveness analysis.
AB  - Cost-effective rollover protective structures (CROPS) are tractor model-specific
      rollover protective structures (ROPS) that are as effective as existing ROPS
      retrofits (passed standardized structural static testing such as SAE J2194), but
      less costly (less than one-half the cost of existing ROPS retrofits). This study
      estimated the expected effects and costs at a per-tractor level for two options:
      No-CROPS and Install-CROPS. Expected injuries per tractor were 0.00169 with no
      CROPS and 0.00016 with CROPS installed, resulting in 0.00153 injuries prevented
      per tractor over a 20-year period. Expected costs were $457 and $248 with and
      without CROPS, respectively, over the same time period, giving the cost per
      injury prevented as $136,601. Comprehensive sensitivity analyses indicated that
      the probability of an overturn is one of the most important variables. When the
      cost of intervention ($1,000 for purchasing, shipping, and installation of ROPS
      retrofit) is used in the analysis, the cost-effectiveness ratio is $497,000 per
      injury prevented over the 20-year period. Thus, installing CROPS instead of
      existing ROPS retrofits improved the cost-effectiveness ratio substantially, with
      a 73% reduction in the net cost per injury prevented.

PMID- 17555206
TI  - A stable dynamic cohort analysis of installing cost-effective rollover protective
      structures (CROPS).
AB  - Cost-effective rollover protective structures (CROPS) are less costly model
      specific rollover protective structure (ROPS) retrofits that are being developed
      and evaluated with the hope of increasing adoption and eventually preventing or
      mitigating injuries due to tractor overturns. A dynamic cohort of the estimated
      retrofittable non-ROPS tractors (accounting for attrition due to aging) was
      tracked over a 20-year period to determine the expected costs, as well as the
      expected number of fatal and non-fatal injuries resulting from tractor overturns.
      Two alternatives were tracked: No-ROPS and Install-CROPS. For a starting cohort
      size of 1,065,164 (an estimate for the year 2004), the Install-CROPS option
      prevented an estimated total of 878 (192 fatal and 686 non-fatal) injuries over
      the 20-year period. Expected costs were $513 million (cost of installing CROPS on
      all the non-ROPS tractors plus cost of the associated injuries) and $284 million
      (cost of injuries resulting from the No-ROPS option) over the same time period.
      Thus, the net cost per injury prevented was $260,820. When the cost of
      intervention ($1000 for purchasing, shipping, and installation of existing ROPS
      retrofit) was used in the analysis, the cost-effectiveness ratio was $927,000 per
      injury prevented over the 20-year period. Thus, installing CROPS instead of
      existing ROPS retrofits improved the cost-effectiveness ratio substantially, with
      a 72% reduction in the net cost per injury prevented.

PMID- 17555207
TI  - Violations of pesticide use and worker safety regulations in North Carolina.
AB  - In North Carolina, responsibility for providing training and enforcing various
      regulations related to pesticide use and agricultural worker safety rests with
      three state agencies. This article summarizes an 11-year history of enforcement
      procedures concerning agricultural pesticide use, the Worker Protection Standard,
      the Hazard Communication Standard, the Migrant Housing Act of North Carolina, and
      field sanitation standards. The difficulty of linking specific types of
      violations with worker safety is discussed.

PMID- 17555208
TI  - Fungicide application practices and personal protective equipment use among
      orchard farmers in the agricultural health study.
AB  - Fungicides are routinely applied to deciduous tree fruits for disease management.
      Seventy-four private orchard applicators enrolled in the Agricultural Health
      Study participated in the Orchard Fungicide Exposure Study in 2002-2003. During
      144 days of observation, information was obtained on chemicals applied and
      applicator mixing, application, personal protective, and hygiene practices. At
      least half of the applicators had orchards with <100 trees. Air blast was the
      most frequent application method used (55%), followed by hand spray (44%). Rubber
      gloves were the most frequently worn protective equipment (68% mix; 59% apply),
      followed by respirators (45% mix; 49% apply), protective outerwear (36% mix; 37%
      apply), and rubber boots (35% mix; 36% apply). Eye protection was worn while
      mixing and applying on only 35% and 41% of the days, respectively. Bivariate
      analyses were performed using repeated logistic or repeated linear regression.
      Mean duration of mixing, pounds of captan applied, total acres sprayed, and
      number of tank mixes sprayed were greater for air blast than for hand spray (p <
      0.05). Spraying from a tractor/vehicle without an enclosed cab was associated
      with wearing some type of coverall (p < 0.05). Applicators often did not wash
      their hands after mixing (77%), a finding not explained by glove use. Glove use
      during mixing was associated with younger age, while wearing long-sleeve shirts
      was associated with older age (p < 0.05 each). Self-reported unusually high
      fungicide exposures were more likely on days applicators performed repairs (p <
      0.05). These data will be useful for evaluating fungicide exposure determinants
      among orchard applicators.

PMID- 17555209
TI  - Effects of management and climate on elk brucellosis in the Greater Yellowstone
      Ecosystem.
AB  - Every winter, government agencies feed approximately 6000 metric tons (6 x 10(6)
      kg) of hay to elk in the southern Greater Yellowstone Ecosystem (GYE) to limit
      transmission of Brucella abortus, the causative agent of brucellosis, from elk to
      cattle. Supplemental feeding, however, is likely to increase the transmission of
      brucellosis in elk, and may be affected by climatic factors, such as snowpack. We
      assessed these possibilities using snowpack and feeding data from 1952 to 2006
      and disease testing data from 1993 to 2006. Brucellosis seroprevalence was
      strongly correlated with the timing of the feeding season. Longer feeding seasons
      were associated with higher seroprevalence, but elk population size and density
      had only minor effects. In other words, the duration of host aggregation and
      whether it coincided with peak transmission periods was more important than just
      the host population size. Accurate modeling of disease transmission depends upon
      incorporating information on how host contact rates fluctuate over time relative
      to peak transmission periods. We also found that supplemental feeding seasons
      lasted longer during years with deeper snowpack. Therefore, milder winters and/or
      management strategies that reduce the length of the feeding season may reduce the
      seroprevalence of brucellosis in the elk populations of the southern GYE.

PMID- 17555210
TI  - Population-level effects of augmented herbivory on Lespedeza cuneata:
      implications for biological control.
AB  - Invasive species pose significant ecological costs, and therefore successful
      management techniques are important. One commonly employed method is biological
      control. The success of biological control depends largely on whether additional
      inflicted damage can successfully reduce the fitness and population growth rate
      of a target species. Here, we simulate herbivory on the invasive Lespedeza
      cuneata and create stage-structured projection models to determine if augmented
      herbivory by a leaf-chewing biological control agent would regulate the
      population growth rate of this species. We found that augmented herbivory
      influenced stage transitions of plants in the smallest stage class, causing
      higher mortality and reduced growth. No other effect was found on stage
      transitions or fecundities, despite manipulation of herbivory at exceptionally
      high levels (up to 80% leaf loss). None of the clipping treatments significantly
      reduced the population growth rate of L. cuneata. We conclude that biological
      control by a leaf chewing herbivore would not likely be successful, even if an
      exceptionally large amount of each plant were consumed. We suggest that this
      approach, a combination of simulated herbivory and demographic modeling, will
      provide essential information for understanding the utility of biological control
      to curb the population growth of invasive plant species.

PMID- 17555211
TI  - Land use change around nature reserves: implications for sustaining biodiversity.

PMID- 17555212
TI  - Ecological mechanisms linking protected areas to surrounding lands.
AB  - Land use is expanding and intensifying in the unprotected lands surrounding many
      of the world's protected areas. The influence of this land use change on
      ecological processes is poorly understood. The goal of this paper is to draw on
      ecological theory to provide a synthetic framework for understanding how land use
      change around protected areas may alter ecological processes and biodiversity
      within protected areas and to provide a basis for identifying scientifically
      based management alternatives. We first present a conceptual model of protected
      areas embedded within larger ecosystems that often include surrounding human land
      use. Drawing on case studies in this Invited Feature, we then explore a
      comprehensive set of ecological mechanisms by which land use on surrounding lands
      may influence ecological processes and biodiversity within reserves. These
      mechanisms involve changes in ecosystem size, with implications for minimum
      dynamic area, species-area effect, and trophic structure; altered flows of
      materials and disturbances into and out of reserves; effects on crucial habitats
      for seasonal and migration movements and population source/sink dynamics; and
      exposure to humans through hunting, poaching, exotics species, and disease. These
      ecological mechanisms provide a basis for assessing the vulnerability of
      protected areas to land use. They also suggest criteria for designing regional
      management to sustain protected areas in the context of surrounding human land
      use. These design criteria include maximizing the area of functional habitats,
      identifying and maintaining ecological process zones, maintaining key migration
      and source habitats, and managing human proximity and edge effects.

PMID- 17555213
TI  - Land change in the southern Yucatan and Calakmul biosphere reserve: effects on
      habitat and biodiversity.
AB  - The southern Yucatan contains the largest expanse of seasonal tropical forests
      remaining in Mexico, forming an ecocline between the drier north of the peninsula
      and the humid Peten, Guatemala. The Calakmul Biosphere Reserve resides in the
      center of this region as part of the Mesoamerican Biological Corridor. The
      reserve's functions are examined in regard to land changes throughout the region,
      generated over the last 40 years by increasing settlement and the expansion and
      intensification of agriculture. These changes are documented from 1987/1988 to
      2000, and their implications regarding the capacity of the reserve to protect the
      ecocline, forest habitats, and butterfly diversity are addressed. The results
      indicate that the current landscape matrix serves the biotic diversity of the
      reserve, with several looming caveats involving the loss of humid forests and the
      interruption of biota flow across the ecocline, and the amount and proximity of
      older forest patches beyond the reserve. The highly dynamic land cover changes
      underway in this economic frontier warrant an adaptive management approach that
      monitors the major changes underway in mature forest types, while the paucity of
      systematic ecological and environment-development studies is rectified in order
      to inform policy and practice.

PMID- 17555214
TI  - Biodiversity consequences of alternative future land use scenarios in Greater
      Yellowstone.
AB  - Land use is rapidly expanding in the Greater Yellowstone Ecosystem, primarily
      from growth in the number of rural homes. There is a need to project possible
      future land use and assess impacts on nature reserves as a guide to future
      management. We assessed the potential biodiversity impacts of alternative future
      land use scenarios in the Greater Yellowstone Ecosystem. An existing regression
      based simulation model was used to project three alternative scenarios of future
      rural home development. The spatial patterns of forecasted development were then
      compared to several biodiversity response variables that included cover types,
      species habitats, and biodiversity indices. We identified the four biodiversity
      responses most at risk of exurban development, designed growth management
      policies to protect these areas, and tested their effectiveness in two
      alternative future scenarios. We found that the measured biodiversity responses,
      including riparian habitat, elk winter range, migration corridors, and eight
      other land cover, habitat, and biodiversity indices, are likely to undergo
      substantial conversion (between 5% and 40%) to exurban development by 2020.
      Future habitat conversion to exurban development outside the region's nature
      reserves is likely to impact wildlife populations within the reserves. Existing
      growth management policies will provide minimal protection to biodiversity in
      this region. We identified specific growth management policies, including
      incentives to cluster future growth near towns, that can protect "at risk"
      habitat types without limiting overall growth in housing.

PMID- 17555215
TI  - Temporal changes in giant panda habitat connectivity across boundaries of Wolong
      Nature Reserve, China.
AB  - Global biodiversity loss is largely driven by human activities such as the
      conversion of natural to human-dominated landscapes. A popular approach to
      mitigating land cover change is the designation of protected areas (e.g., nature
      reserves). Nature reserves are traditionally perceived as strongholds of
      biodiversity conservation. However, many reserves are affected by land cover
      changes not only within their boundaries, but also in their surrounding areas.
      This study analyzed the changes in habitat for the giant panda (Ailuropoda
      melanoleuca) inside Wolong Nature Reserve, Sichuan, China, and in a 3-km buffer
      area outside its boundaries, through a time series of classified satellite
      imagery and field observations. Habitat connectivity between the inside and the
      outside of the reserve diminished between 1965 and 2001 because panda habitat was
      steadily lost both inside and outside the reserve. However, habitat connectivity
      slightly increased between 1997 and 2001 due to the stabilization of some panda
      habitat inside and outside the reserve. This stabilization most likely occurred
      as a response to changes in socioeconomic activities (e.g., shifts from
      agricultural to nonagricultural economies). Recently implemented government
      policies could further mitigate the impacts of land cover change on panda
      habitat. The results suggest that Wolong Nature Reserve, and perhaps other nature
      reserves in other parts of the world, cannot be managed as an isolated entity
      because habitat connectivity declines with land cover changes outside the reserve
      even if the area inside the reserve is well protected. The findings and
      approaches presented in this paper may also have important implications for the
      management of other nature reserves across the world.

PMID- 17555216
TI  - Land use change around protected areas: management to balance human needs and
      ecological function.
AB  - Protected areas throughout the world are key for conserving biodiversity, and
      land use is key for providing food, fiber, and other ecosystem services essential
      for human sustenance. As land use change isolates protected areas from their
      surrounding landscapes, the challenge is to identify management opportunities
      that maintain ecological function while minimizing restrictions on human land
      use. Building on the case studies in this Invited Feature and on ecological
      principles, we identify opportunities for regional land management that maintain
      both ecological function in protected areas and human land use options, including
      preserving crucial habitats and migration corridors, and reducing dependence of
      local human populations on protected area resources. Identification of
      appropriate and effective management opportunities depends on clear definitions
      of: (1) the biodiversity attributes of concern; (2) landscape connections to
      delineate particular locations with strong ecological interactions between the
      protected area and its surrounding landscape; and (3) socioeconomic dynamics that
      determine current and future use of land resources in and around the protected
      area.

PMID- 17555217
TI  - Fishing the line near marine reserves in single and multispecies fisheries.
AB  - Throughout the world "fishing the line" is a frequent harvesting tactic in
      communities where no-take marine reserves are designated. This practice of
      concentrating fishing effort at the boundary of a marine reserve is predicated
      upon the principle of spillover, the net export of stock from the marine reserve
      to the surrounding unprotected waters. We explore the consequences and optimality
      of fishing the line using a spatially explicit theoretical model. We show that
      fishing the line: (1) is part of the optimal effort distribution near no-take
      marine reserves with mobile species regardless of the cooperation level among
      harvesters; (2) has a significant impact on the spatial patterns of catch per
      unit effort (CPUE) and fish density both within and outside of the reserve; and
      (3) can enhance total population size and catch simultaneously under a limited
      set of conditions for overexploited populations. Additionally, we explore the
      consequences of basing the spatial distribution of fishing effort for a
      multispecies fishery upon the optimality of the most mobile species that exhibits
      the greatest spillover. Our results show that the intensity of effort allocated
      to fishing the line should instead be based upon more intermediate rates of
      mobility within the targeted community. We conclude with a comparison between
      model predictions and empirical findings from a density gradient study of two
      important game fish in the vicinity of a no-take marine-life refuge on Santa
      Catalina Island, California (USA). These results reveal the need for empirical
      studies to account for harvester behavior and suggest that the implications of
      spatial discontinuities such as fishing the line should be incorporated into
      marine-reserve design.

PMID- 17555218
TI  - Toward pristine biomass: reef fish recovery in coral reef marine protected areas
      in Kenya.
AB  - Identifying the rates of recovery of fish in no-take areas is fundamental to
      designing protected area networks, managing fisheries, estimating yields,
      identifying ecological interactions, and informing stakeholders about the
      outcomes of this management. Here we study the recovery of coral reef fishes
      through 37 years of protection using a space-for-time chronosequence of four
      marine national parks in Kenya. Using AIC model selection techniques, we assessed
      recovery trends using five ecologically meaningful production models: asymptotic,
      Ricker, logistic, linear, and exponential. There were clear recovery trends with
      time for species richness, total and size class density, and wet masses at the
      level of the taxonomic family. Species richness recovered rapidly to an asymptote
      at 10 years. The two main herbivorous families displayed differing responses to
      protection, scarids recovering rapidly, but then exhibiting some decline while
      acanthurids recovered more slowly and steadily throughout the study. Recovery of
      the two invertebrate-eating groups suggested competitive interactions over
      resources, with the labrids recovering more rapidly before a decline and the
      balistids demonstrating a slower logistic recovery. Remaining families displayed
      differing trends with time, with a general pattern of decline in smaller size
      classes or small-bodied species after an initial recovery, which suggests that
      some species- and size-related competitive and predatory control occurs in older
      closures. There appears to be an ecological succession of dominance with an
      initial rapid rise in labrids and scarids, followed by a slower rise in balistids
      and acanthurids, an associated decline in sea urchins, and an ultimate dominance
      in calcifying algae. Our results indicate that the unfished "equilibrium" biomass
      of the fish assemblage > 10 cm is 1100-1200 kg/ha, but these small parks (< 10
      km2) are likely to underestimate pre-human influence values due to edge effects
      and the rarity of taxa with large area requirement, such as apex predators,
      including sharks.

PMID- 17555219
TI  - Evaluating tributary restoration potential for Pacific salmon recovery.
AB  - Although habitat restoration can play a key role in the conservation of imperiled
      species, for animals that demonstrate long migrations and complex life histories,
      reliance on physical restoration of isolated habitat patches comes with
      considerable uncertainty. Nevertheless, within freshwater ecosystems, stream
      restoration has become a major conservation focus, with millions of dollars spent
      annually on efforts aimed at recovering degraded habitat and imperiled riverine
      species. Within this context, we addressed fundamental uncertainties of the focus
      on tributary restoration for recovery of salmon: (1) Is there potential for
      improving habitat in tributaries? (2) What magnitude of early survival
      improvement can be expected based on stream restoration? and (3) Will incremental
      increases in early survival be sufficient to ensure viability overall? We
      combined simple mechanistic habitat models, population viability measures, and
      categorical filters to quantify "restoration potential," expressed as increased
      total life-cycle survival in response to restored tributary condition, across 32
      populations composing five major population groups (MPG). A wide gap remains
      between how much survival improvement is needed vs. what is likely to occur;
      restoration potential meets the necessary minimum increase needed for only four
      populations within one MPG. The remaining populations (84%, 4 MPG) still fall far
      below the survival increase needed for future viability. In addition, across all
      populations and groups, a 171% increase (on average) in total life-cycle survival
      is needed; only approximately 106% appears possible. A recovery strategy for
      these salmon that relies largely on tributary restoration to mitigate for known
      mortality imposed at other life stages (e.g., migration through hydropower dams)
      is risky with a low probability of success. We demonstrate an approach for
      completing an a priori evaluation of restoration potential linked to population
      viability, such that habitat restoration efforts can be biologically prioritized
      and scarce resources can be allocated to efforts with the greatest potential and
      the least amount of risk, in terms of meeting conservation and recovery goals.

PMID- 17555220
TI  - Stream ecosystem response to limestone treatment in acid impacted watersheds of
      the Allegheny Plateau.
AB  - Restoration programs are expanding worldwide, but assessments of restoration
      effectiveness are rare. The objectives of our study were to assess current acid
      precipitation remediation programs in streams of the Allegheny Plateau ecoregion
      of West Virginia (USA), identify specific attributes that could and could not be
      fully restored, and quantify temporal trends in ecosystem recovery. We sampled
      water chemistry, physical habitat, periphyton biomass, and benthic
      macroinvertebrate and fish community structure in three stream types: acidic
      (four streams), naturally circumneutral (eight streams), and acidic streams
      treated with limestone sand (eight streams). We observed no temporal trends in
      ecosystem recovery in treated streams despite sampling streams that ranged from 2
      to 20 years since initial treatment. Our results indicated that the application
      of limestone sand to acidic streams was effective in fully recovering some
      characteristics, such as pH, alkalinity, Ca2+, Ca:H ratios, trout biomass and
      density, and trout reproductive success. However, recovery of many other
      characteristics was strongly dependent upon spatial proximity to treatment, and
      still others were never fully recovered. For example, limestone treatment did not
      restore dissolved aluminum concentrations, macroinvertebrate taxon richness, and
      total fish biomass to circumneutral reference conditions. Full recovery may not
      be occurring because treated streams continue to drain acidic watersheds and
      remain isolated in a network of acidic streams. We propose a revised stream
      restoration plan for the Allegheny Plateau that includes restoring stream
      ecosystems as connected networks rather than isolated reaches and recognizes that
      full recovery of acidified watersheds may not be possible.

PMID- 17555221
TI  - Zooplankton community resilience after press-type anthropogenic stress in
      temporary ponds.
AB  - Temporary ponds are physically disturbed environments that fluctuate on seasonal
      and interannual scales. These ecosystems are also susceptible to anthropogenic
      perturbation such as contamination inputs. However, the interactive effects of
      natural disturbance and anthropogenic stress on ecosystem processes and community
      dynamics have hardly been assessed in these ecosystem types. We used a multiple
      before-after control-impact (MBACI) design to study zooplankton community
      recovery from low and high inputs of a fire retardant in artificially constructed
      ponds over three hydroperiods. The retardant caused a decline in species richness
      and an increase in rotifers during summer and winter months relative to controls
      and pretreatment dates, and the duration of these changes varied among retardant
      treatments. In nonmetric, multidimensional scaling analyses the increased rotifer
      densities were reflected in loops that showed recurring deviations from and (upon
      collapse) approaches to reference conditions, while the effects of the
      anthropogenic stressor persisted in the ponds. The amplitudes of fluctuation
      followed no regular patterns; it varied with retardant treatment level and was
      higher in the third hydroperiod compared to the second in one of the treatments.
      From a temporal perspective, this non-dampened pattern suggests a new cause
      effect mechanism for disturbance ecology, which we refer to as a "protracted
      press disturbance, roller coaster response" relationship. This model emphasizes
      stochastic oscillations in community composition, punctuated by periods in which
      the community approaches reference conditions. From the applied viewpoint, this
      model suggests that the accurate detection of perturbation and the implementation
      of sound management and restoration strategies will require intensive sampling
      designs that span multiple hydroperiods in persistently degraded ponds.

PMID- 17555222
TI  - Adaptive reversals in acid tolerance in copepods from lakes recovering from
      historical stress.
AB  - Anthropogenic habitat disturbance can often lead to rapid evolution of
      environmental tolerances in taxa that are able to withstand the stressor. What we
      do not understand, however, is how species respond when the stressor no longer
      exists, especially across landscapes and over a considerable length of time. Once
      anthropogenic disturbance is removed and if there is an ecological trade-off
      associated with local adaptation to such an historical stressor, then
      evolutionary theory would predict evolutionary reversals. On the Boreal Shield,
      tens of thousands of lakes acidified as a result of SO2 emissions, but many of
      these lakes are undergoing chemical recovery as a consequence of reduced
      emissions. We investigated the adaptive consequences of disturbance and recovery
      to zooplankton living in these lakes by asking (1) if contemporary evolution of
      acid tolerance had arisen among Leptodiaptomus minutus copepod populations in
      multiple circum-neutral lakes with and without historical acidification, (2) if
      L. minutus populations were adaptively responding to reversals in selection in
      historically acidified lakes that had recovered to pH 6.0 for at least 6-8 years,
      and (3) if there was a fitness trade-off for L. minutus individuals with high
      acid tolerance at circum-neutral pH. L. minutus populations had higher acid
      tolerances in circum-neutral lakes with a history of acidification than in local
      and distant lakes that were never acidified. However, copepods in circum-neutral
      acid-recovering lakes were less acid-tolerant than were copepods in lakes with
      longer recovery time. This adaptive reversal in acid tolerance of L. minutus
      populations following lake recovery was supported by the results of a laboratory
      experiment that indicated a fitness trade-off in copepods with high acid
      tolerances at circum-neutral pH. These responses appear to have a genetic basis
      and suggest that L. minutus is highly adaptive to changes in environmental
      conditions. Therefore, restoration managers should focus on removing
      environmental stressors, and adaptable species will be able to reverse
      evolutionary responses to environmental disturbance in the years following
      recovery.

PMID- 17555223
TI  - Sources and dynamics of large logs in a temperate floodplain river.
AB  - Large logs, important agents of biophysical heterogeneity in temperate floodplain
      rivers, have been virtually eliminated from modified systems. Our purpose was to
      quantify the sources and dynamics of large logs (> or = 1 m diameter) in the
      mainstem of a nearly pristine system: the Queets River, Washington, USA. Erosion
      of forests by the river supplies 0.40 logs x (100 m)(-1) x yr(-1) to the channel.
      Most (72%) are new logs entering the river for the first time as the river
      undercuts mature fluvial terraces dominated by large conifers. Retrospective
      airphoto analyses demonstrate that, over 63 years, the Queets River recruits 95%
      of new logs from a riparian corridor extending 265 m laterally on both banks,
      mostly through channel meandering. However, input rates are patchy, with 10% of
      the valley length supplying 38% of the new logs. As the river moves laterally,
      remnant logs are left on channel surfaces that later develop riparian forests and
      reenter the river when those forests erode. Remnant logs lying on the floodplain
      forest floor surface or buried in alluvium constitute 21% and 7% of the annual
      inputs from bank erosion, respectively. We estimate that 50% of logs deposited in
      the channel in a given year, including those underpinning logjams, are
      transported downriver within five years. Over the next 55 years, bank erosion
      reclaims an additional 23%, leaving 27% of the logs stable for > 60 years.
      Simulations indicate that recurrent transport is common, with half of the large
      conifers being deposited in > or = 3 locations and transported > or = 1.5 km
      prior to disintegrating. One in ten logs links distant reaches by occupying > or
      = 7 locations spanning > or = 12.0 km. Instream supplies are therefore a mixture
      of new and old logs from nearby and upstream forests, sustained by the recapture
      and transport of stockpiled remnant logs during periods when new inputs are low.
      We propose that patchy input rates and the periodic rearrangement of large logs
      are important drivers of temporal variation in river valley habitats, adding to
      the spatial complexity created by stable logs. These findings underscore the
      importance of extensive mature forests and connectivity in temperate floodplain
      rivers.

PMID- 17555224
TI  - Urbanization and nutrient retention in freshwater riparian wetlands.
AB  - Urbanization can degrade water quality and alter watershed hydrology, with
      profound effects on the structure and function of both riparian wetlands (RWs)
      and aquatic ecosystems downstream. We used freshwater RWs in Fairfax County,
      Virginia, USA, as a model system to examine: (1) the effects of increasing
      urbanization (indexed by the percentage of impervious surface cover [%ISC] in the
      surrounding watershed) on nitrogen (N) and phosphorus (P) concentrations in
      surface soils and plant tissues, soil P saturation, and soil iron (Fe) chemistry;
      and (2) relationships between RW soil and plant nutrient chemistries vs. the
      physical and biotic integrity of adjacent streams. Soil total P and NaOH
      extractable P (representing P bound to aluminum [Al] and Fe hydrous oxides)
      varied significantly but nonlinearly with % ISC (r2 = 0.69 and 0.57,
      respectively); a similar pattern was found for soil P saturation but not for soil
      total N. Relationships were best described by second-order polynomial equations.
      Riparian wetlands appear to receive greater P loads in moderately (8.6-13.3% ISC)
      than in highly (25.1-29.1% ISC) urbanized watersheds. These observations are
      consistent with alterations in watershed hydrology that occur with increasing
      urbanization, directing water and nutrient flows away from natural RWs.
      Significant increases in total and crystalline soil Fe (r2 = 0.57 and 0.53,
      respectively) and decreases in relative soil Fe crystallinity with increasing
      %ISC suggest the mobilization and deposition of terrestrial sediments in RWs,
      likely due to construction activities in the surrounding watershed. Increases in
      RW plant tissue nutrient concentrations and %ISC in the surrounding watershed
      were negatively correlated with standard indices of the physical and biotic
      integrity of adjacent streams. In combination, these data suggest that nutrient
      and sediment inputs associated with urbanization and storm-water management are
      important variables that affect wetland ecosystem services, such as water quality
      improvement, in urbanizing landscapes.

PMID- 17555225
TI  - Tsuga canadensis (L.) Carr. mortality will impact hydrologic processes in
      southern Appalachian forest ecosystems.
AB  - Eastern hemlock (Tsuga canadensis (L.) Carr.) is one of the principal riparian
      and cove canopy species in the southern Appalachian Mountains. Throughout its
      range, eastern hemlock is facing potential widespread mortality from the hemlock
      woolly adelgid (HWA). If HWA-induced eastern hemlock mortality alters hydrologic
      function, land managers will be challenged to develop management strategies that
      restore function or mitigate impacts. To estimate the impact that the loss of
      this forest species will have on the hydrologic budget, we quantified and modeled
      transpiration over a range of tree sizes and environmental conditions. We used
      heat dissipation probes, leaf-level gas-exchange measurements, allometric
      scaling, and time series modeling techniques to quantify whole-tree and leaf
      level transpiration (E(L)) of eastern hemlock. We monitored trees ranging from
      9.5 to 67.5 cm in diameter along a riparian corridor in western North Carolina,
      USA during 2004 and 2005. Maximum rates of daily tree water use varied by
      diameter and height, with large trees transpiring a maximum of 178-186 kg H2O x
      tree(-1) x d(-1). Values of E(L) could be predicted from current and lagged
      environmental variables. We forecasted eastern hemlock E(L) for inventoried
      stands and estimated a mean annual transpiration rate of 63.3 mm/yr for the
      hemlock component, with 50% being transpired in the winter and spring. In typical
      southern Appalachian stands, eastern hemlock mortality would thus reduce annual
      stand-level transpiration by approximately 10% and reduce winter and spring stand
      level transpiration by approximately 30%. Eastern hemlock in the southern
      Appalachians has two distinct ecohydrological roles: an evergreen tree that
      maintains year-round transpiration rates and a riparian tree that has high
      transpiration rates in the spring. No other native evergreen in the southern
      Appalachians will likely fill the ecohydrological role of eastern hemlock if
      widespread mortality occurs. With the loss of this species, we predict persistent
      increases in discharge, decreases in the diurnal amplitude of streamflow, and
      increases in the width of the variable source area.

PMID- 17555226
TI  - Headwater riparian forest-floor invertebrate communities associated with
      alternative forest management practices.
AB  - Headwater streams and their riparian zones are a common, yet poorly understood,
      component of Pacific Northwest, USA, landscapes. We describe the ecological
      importance of headwater stream riparian zones as habitat for forest-floor
      invertebrate communities and assess how alternative management strategies for
      riparian zones may impact these communities. We compared community composition of
      forest-floor invertebrates at increasing distances along trans-riparian (stream
      edge to upslope) transects in mature forests, clearcuts, and riparian buffers of
      approximately 30-m width with upslope clearcuts. Invertebrates were collected
      using pitfall traps in five replicate blocks of three treatments each in the
      Willamette National Forest, Oregon, USA. We measured microclimate and
      microhabitat variables at pitfall locations. Despite strong elevation and block
      effects on community composition, community analyses revealed a distinct
      "riparian" invertebrate community within 1 m of the stream edge in mature forest
      treatments, which was strongly related to cool, humid microclimate conditions.
      Invertebrate community composition in buffer treatments was far more similar to
      that of mature forests than to clearcuts; a pattern mirrored by microclimate.
      These results suggest that, within our study sites, forest-floor invertebrate
      distributions are strongly associated with microclimate and that riparian buffers
      of approximately 30-m width do provide habitat for many riparian and forest
      species. Riparian reserves may serve as effective forest refugia and/or dispersal
      corridors for invertebrates and other taxa, and their incorporation into
      watershed management plans likely will contribute to meeting persistence and
      connectivity objectives.

PMID- 17555227
TI  - Bird species and traits associated with logged and unlogged forest in Borneo.
AB  - The ecological consequences of logging have been and remain a focus of
      considerable debate. In this study, we assessed bird species composition within a
      logging concession in Central Kalimantan, Indonesian Borneo. Within the study
      area (approximately 196 km2) a total of 9747 individuals of 177 bird species were
      recorded. Our goal was to identify associations between species traits and
      environmental variables. This can help us to understand the causes of disturbance
      and predict whether species with given traits will persist under changing
      environmental conditions. Logging, slope position, and a number of habitat
      structure variables including canopy cover and liana abundance were significantly
      related to variation in bird composition. In addition to environmental variables,
      spatial variables also explained a significant amount of variation. However,
      environmental variables, particularly in relation to logging, were of greater
      importance in structuring variation in composition. Environmental change
      following logging appeared to have a pronounced effect on the feeding guild and
      size class structure but there was little evidence of an effect on restricted
      range or threatened species although certain threatened species were adversely
      affected. For example, species such as the terrestrial insectivore Argusianus
      argus and the hornbill Buceros rhinoceros, both of which are threatened, were
      rare or absent in recently logged forest. In contrast, undergrowth insectivores
      such as Orthotomus atrogularis and Trichastoma rostratum were abundant in
      recently logged forest and rare in unlogged forest. Logging appeared to have the
      strongest negative effect on hornbills, terrestrial insectivores, and canopy bark
      gleaning insectivores while moderately affecting canopy foliage-gleaning
      insectivores and frugivores, raptors, and large species in general. In contrast,
      undergrowth insectivores responded positively to logging while most understory
      guilds showed little pronounced effect. Despite the high species richness of
      logged forest, logging may still have a negative impact on extant diversity by
      adversely affecting key ecological guilds. The sensitivity of hornbills in
      particular to logging disturbance may be expected to alter rainforest dynamics by
      seriously reducing the effective seed dispersal of associated tree species.
      However, logged forest represents an increasingly important habitat for most bird
      species and needs to be protected from further degradation. Biodiversity
      management within logging concessions should focus on maintaining large areas of
      unlogged forest and mitigating the adverse effects of logging on sensitive groups
      of species.

PMID- 17555228
TI  - Long-term CO2 enrichment of a forest ecosystem: implications for forest
      regeneration and succession.
AB  - The composition and successional status of a forest affect carbon storage and net
      ecosystem productivity, yet it remains unclear whether elevated atmospheric
      carbon dioxide (CO2) will impact rates and trajectories of forest succession. We
      examined how CO2 enrichment (+200 microL CO2/L air differential) affects forest
      succession through growth and survivorship of tree seedlings, as part of the Duke
      Forest free-air CO2 enrichment (FACE) experiment in North Carolina, USA. We
      planted 2352 seedlings of 14 species in the low light forest understory and
      determined effects of elevated CO2 on individual plant growth, survival, and
      total sample biomass accumulation, an integrator of plant growth and survivorship
      over time, for six years. We used a hierarchical Bayes framework to accommodate
      the uncertainty associated with the availability of light and the variability in
      growth among individual plants. We found that most species did not exhibit strong
      responses to CO2. Ulmus alata (+21%), Quercus alba (+9.5%), and nitrogen-fixing
      Robinia pseudoacacia (+230%) exhibited greater mean annual relative growth rates
      under elevated CO2 than under ambient conditions. The effects of CO2 were small
      relative to variability within populations; however, some species grew better
      under low light conditions when exposed to elevated CO2 than they did under
      ambient conditions. These species include shade-intolerant Liriodendron
      tulipifera and Liquidambar styraciflua, intermediate-tolerant Quercus velutina,
      and shade-tolerant Acer barbatum, A. rubrum, Prunus serotina, Ulmus alata, and
      Cercis canadensis. Contrary to our expectation, shade-intolerant trees did not
      survive better with CO2 enrichment, and population-scale responses to CO2 were
      influenced by survival probabilities in low light. CO2 enrichment did not
      increase rates of sample biomass accumulation for most species, but it did
      stimulate biomass growth of shade-tolerant taxa, particularly Acer barbatum and
      Ulmus alata. Our data suggest a small CO2 fertilization effect on tree
      productivity, and the possibility of reduced carbon accumulation rates relative
      to today's forests due to changes in species composition.

PMID- 17555229
TI  - Potential effects of environmental contamination on Yuma Myotis demography and
      population growth.
AB  - Unplanned natural and anthropogenic disasters provide unique opportunities for
      investigating the influence of perturbations on population vital rates and
      species recovery times. We investigated the potential effects of a major
      pesticide spill by comparing annual survival rates using mark-recapture
      techniques on a riparian bat species, Yuma Myotis (Myotis yumanensis). Demography
      and population dynamics for most bat species remain poorly understood despite
      advances in mark-recapture estimation and modeling techniques. We compared
      survival and population growth rates of two roost populations exposed to a large
      chemical (metam sodium) spill in the upper Sacramento River in Northern
      California with two roost populations outside the contaminated area from 1992 to
      1996. Hypotheses about long-term effects of the spill on female juvenile and
      adult survival were tested using an information-theoretic approach (AIC). Working
      hypotheses included effects of age, chemical spill, and time trend on survival.
      Female adult survival was higher than female juvenile survival across all sites,
      suggesting stage-specific mortality risks. Model-averaged estimates of female
      juvenile survival in the contaminated area (0.50-0.74) were lower than in control
      roosts (0.60-0.78) for each year in the study, suggesting that the spill may have
      reduced juvenile survival for several years. Female adult survival (0.73-0.89)
      did not appear to be strongly affected by the spill during the years of the
      study. There was an increase in survival for both stage-classes across all
      populations during the study period, which may have been caused by the end of an
      extended drought in California in the winter of 1993. The spill-affected
      population was in decline for the first year of the study as indicated by an
      estimated growth rate (lambda) < 1, but population growth rates increased during
      the four-year period.

PMID- 17555230
TI  - Satellite telemetry and prey sampling reveal contaminant sources to Pacific
      Northwest Ospreys.
AB  - Migratory behavior can be an important factor in determining contaminant exposure
      in avian populations. Accumulation of organochlorine (OC) pesticides while birds
      are wintering in tropical regions has been cited often as the reason for high
      concentrations in migrant populations. To explore this issue, we satellite
      tracked 16 Ospreys (Pandion haliaetus) over the period 1996-2003 from breeding
      sites in British Columbia, Canada, and integrated the results into a database on
      15 Ospreys that were satellite tracked over the period 1995-1999, from breeding
      locations in Washington and Oregon, USA. Data on wintering sites of 31 Ospreys in
      Mexico and Central America were used for spatially targeted sampling of prey
      fish. Concentrations of the main organochlorine contaminant, p,p'-dichloro
      diphenyl-dichloroethylene (DDE), in fish composites from Mexico ranged from 0.005
      to 0.115 nicrog/g wet mass. Significant differences existed among fish families
      in p,p'-DDE, total dichloro-diphenyl-trichloroethane (sigmaDDT), sigmachlordanes,
      and total polychlorinated biphenyls (sigmaPCBs). Catfish (family Ariidae)
      generally had significantly higher levels of DDT metabolites and other
      organochlorine contaminants compared to other fish families collected.
      Differences in prey contaminant levels were detected among the collection sites
      around coastal Mexico, with fish from Veracruz State generally having higher
      levels of DDT metabolites, sigmachlordanes, sigmaPCBs, and hexachlorobenzene.
      Eggs collected from 16 nests throughout the Pacific Northwest (nine from British
      Columbia, seven from Oregon and Washington) where Ospreys had been satellite
      tagged, showed marked variation in levels of DDT metabolites (p,p'-DDE; range
      0.02-10.14 microg/g). Wintering site had no significant effect on contaminant
      concentrations in sample eggs from those specific Ospreys; rather concentrations
      of p,p'-DDE, were predicted by breeding sites with highest levels in eggs of
      Ospreys breeding in the lower Columbia River, consistent with published reports
      of continued high concentrations of DDT and related compounds in that system.

PMID- 17555231
TI  - The effect of wind direction on cross-pollination in wind-pollinated GM crops.
AB  - In Europe, regulatory thresholds restrict adventitious GM (genetically modified)
      presence in conventional crops. Minimum distances for the spatial separation of
      fields are often recommended to reduce field-to-field cross-pollination to an
      acceptable level. Field trials are typically the basis for setting separation
      distances. However, using records of wind direction and speed from weather
      stations across Europe, we predict theoretically that field-to-field windborne
      cross-pollination in maize, oilseed rape, sugar beet, and rice varies greatly
      according to the relative orientation of the GM and non-GM fields. Furthermore,
      at a given site and orientation from a GM field, we predict that the cross
      pollination rate varies substantially from year to year. Consequently, even
      replicated field trials may inaccurately estimate typical levels of cross
      pollination and therefore distort our perception of the separation distances
      required to achieve sub-threshold adventitious GM presence. We propose methods to
      predict the likely range in levels of cross-pollination based on the limited data
      typically available from field trials. Additionally, we suggest suitable time
      lags between peak flowering in adjacent fields that could be introduced to reduce
      cross-pollination to a specified level.

PMID- 17555232
TI  - Long-distance GM pollen movement of creeping bentgrass using modeled wind
      trajectory analysis.
AB  - The importance of understanding the role of atmospheric conditions in pollen
      dispersal has grown in recent years with increased field-testing of genetically
      modified (GM) crop plants. An atmospheric model was used to characterize wind
      trajectories at 10 m and 100 m above GM pollen source fields located within a
      4452-ha "control" area north of Madras, Oregon, USA, designated by the Oregon
      Department of Agriculture (ODA). The area was used in 2003 for the growth of GM
      creeping bentgrass (Agrostis stolonifera) engineered to be resistant to
      glyphosate herbicide. The presence of the GM gene (CP4 EPSPS) provided a distinct
      selectable marker for pollen-mediated gene flow to sentinel and resident Agrostis
      spp. plants. Linkage of GM gene presence with wind flow characteristics over the
      "control" area became essential to understand the timing and processes leading to
      long-distance transport of this pollen. Wind trajectories showed a general
      pattern of northwest to southeast air movement. Trajectory travel distances
      calculated hourly from 06:00 hours to 15:00 hours during the 2003 pollination
      period (15 June-15 July) showed movement up to 15 km from the "control" area's
      center by the first hour. Maximum travel distances increased to 40 and 55 km
      after two and three hours from release, respectively. Calculated wind trajectory
      positions corresponded with observed long-distance pollen-mediated gene flow in
      the seedlings of sentinel and resident plants. The highest correlations were
      found during the late morning hours. Back-calculated wind trajectories from
      sentinel and resident locations with GM-gene-positive progeny suggested that most
      successful fertilizations occurred in the direction of prevailing winds during
      late June 2003. The occurrence of positive progeny from sentinel plants, upwind
      of the "control" area during this period, indicated the additional influence of
      local topography on pollen dispersal.

PMID- 17555233
TI  - Point/counterpoint. Simultaneous PET/MR will replace PET/CT as the molecular
      multimodality imaging platform of choice.

PMID- 17555234
TI  - Quality in radiation oncology.
AB  - A modern approach to quality was developed in the United States at Bell Telephone
      Laboratories during the first part of the 20th century. Over the years, those
      quality techniques have been adopted and extended by almost every industry.
      Medicine in general and radiation oncology in particular have been slow to adopt
      modern quality techniques. This work contains a brief description of the history
      of research on quality that led to the development of organization-wide quality
      programs such as Six Sigma. The aim is to discuss the current approach to quality
      in radiation oncology as well as where quality should be in the future. A
      strategy is suggested with the goal to provide a threshold improvement in quality
      over the next 10 years.

PMID- 17555235
TI  - Slit design for efficient and accurate MTF measurement at megavoltage x-ray
      energies.
AB  - Empirical determination of the modulation transfer function (MTF) for analog and
      digital mega-voltage x-ray imagers is a challenging task. The most common method
      used to determine MTF at megavoltage x-ray energies employs a long, narrow slit
      formed by two parallel, metal blocks in order to form a "slit beam." In this
      work, a detailed overview of some of the important considerations of slit design
      is presented. Based on these considerations, a novel, compact slit, using 19 cm
      thick tungsten blocks, was designed. The prototype slit was configured to attach
      to the accessory slot of the gantry of a linear accelerator, which greatly
      simplified the measurement process. Measurements were performed to determine the
      presampling MTF at 6 MV for an indirect detection active matrix flat panel imager
      prototype previously developed for megavoltage imaging applications. In addition,
      the effects of two important slit design parameters, material type and thickness,
      on the accuracy of MTF determination were investigated via a Monte Carlo-based
      theoretical study. Empirically determined MTFs obtained from the prototype slit
      closely match those from an earlier, less compact slit design based on 40 cm
      thick steel blocks. The results of the Monte Carlo-based theoretical studies
      indicate that the prototype slit achieves close-to-ideal performance in terms of
      accurately determining the MTF by virtue of practically 100% beam attenuation in
      regions other than the slit gap. Furthermore, the theoretical results suggest
      that it may be possible to achieve even further reductions in slit thickness
      without compromising measurement accuracy.

PMID- 17555237
TI  - Nonparametric ROC and LROC analysis.
AB  - In this paper we review several results of the nonparametric receiver operating
      characteristic (ROC) analysis and present an extension to the nonparametric
      localization ROC (LROC) analysis. Equations for the estimation of the area under
      the characteristic curve and for the variance calculations are derived.
      Expressions for the choice of the optimal ratio between the number of signal
      absent and signal-present image samples are also presented. The results can be
      applied both with continuous or discrete scoring scales. The simulation studies
      carried out validate the theoretical derivations and show that the LROC analysis
      is considerably more sensitive than the ROC analysis.

PMID- 17555238
TI  - A simple device for high-precision head image registration: preliminary
      performance and accuracy tests.
AB  - The purpose of this paper is to present a new device for multimodal head study
      registration and to examine its performance in preliminary tests. The device
      consists of a system of eight markers fixed to mobile carbon pipes and bars which
      can be easily mounted on the patient's head using the ear canals and the nasal
      bridge. Four graduated scales fixed to the rigid support allow examiners to find
      the same device position on the patient's head during different acquisitions. The
      markers can be filled with appropriate substances for visualisation in computed
      tomography (CT), magnetic resonance, single photon emission computer tomography
      (SPECT) and positron emission tomography images. The device's rigidity and its
      position reproducibility were measured in 15 repeated CT acquisitions of the
      Alderson Rando anthropomorphic phantom and in two SPECT studies of a patient. The
      proposed system displays good rigidity and reproducibility characteristics. A
      relocation accuracy of less than 1,5 mm was found in more than 90% of the
      results. The registration parameters obtained using such a device were compared
      to those obtained using fiducial markers fixed on phantom and patient heads,
      resulting in differences of less than 1 degree and 1 mm for rotation and
      translation parameters, respectively. Residual differences between fiducial
      marker coordinates in reference and in registered studies were less than 1 mm in
      more than 90% of the results, proving that the device performed as accurately as
      noninvasive stereotactic devices. Finally, an example of multimodal employment of
      the proposed device is reported.

PMID- 17555236
TI  - Tomographic digital subtraction angiography for lung perfusion estimation in
      rodents.
AB  - In vivo measurements of perfusion present a challenge to existing small animal
      imaging techniques such as magnetic resonance microscopy, micro computed
      tomography, micro positron emission tomography, and microSPECT, due to combined
      requirements for high spatial and temporal resolution. We demonstrate the use of
      tomographic digital subtraction angiography (TDSA) for estimation of perfusion in
      small animals. TDSA augments conventional digital subtraction angiography (DSA)
      by providing three-dimensional spatial information using tomosynthesis
      algorithms. TDSA is based on the novel paradigm that the same time density curves
      can be reproduced in a number of consecutive injections of microL volumes of
      contrast at a series of different angles of rotation. The capabilities of TDSA
      are established in studies on lung perfusion in rats. Using an imaging system
      developed in-house, we acquired data for four-dimensional (4D) imaging with
      temporal resolution of 140 ms, in-plane spatial resolution of 100 microm, and
      slice thickness on the order of millimeters. Based on a structured experimental
      approach, we optimized TDSA imaging providing a good trade-off between slice
      thickness, the number of injections, contrast to noise, and immunity to
      artifacts. Both DSA and TDSA images were used to create parametric maps of
      perfusion. TDSA imaging has potential application in a number of areas where
      functional perfusion measurements in 4D can provide valuable insight into animal
      models of disease and response to therapeutics.

PMID- 17555239
TI  - Relative output factor and beam profile measurements of small radiation fields
      with an L-alanine/K-band EPR minidosimeter.
AB  - The performance of an L-alanine dosimeter with millimeter dimensions was
      evaluated for dosimetry in small radiation fields. Relative output factor (ROF)
      measurements were made for 0.5 x 0.5, 1 x 1, 3 x 3, 5 x 5, 10 x 10 cm(2) square
      fields and for 5-, 10-, 20-, 40-mm-diam circular fields. In beam profile (BP)
      measurements, only 1 x 1, 3 x 3, 5 x 5 cm2 square fields and 10-, 20-, 40-mm-diam
      circular fields were used. For square and circular field irradiations,
      Varian/Clinac 2100, and a Siemens/Mevatron 6 MV linear accelerators were used,
      respectively. For a batch of 800 L-alanine minidosimeters (miniALAs) the average
      mass was 4.3+/-0.5 (1 sigma) mg, the diameter was 1.22+/-0.07 (1 sigma) mm, and
      the length was 3.5+/-0.2 (l sigma) mm. A K-Band (24 GHz) electron paramagnetic
      resonance (EPR) spectrometer was used for recording the spectrum of irradiated
      and nonirradiated miniALAs. To evaluate the performance of the miniALAs, their
      ROF and BP results were compared with those of other types of detectors, such as
      an ionization chamber (PTW 0.125 cc), a miniTLD (LiF: Mg,Cu,P), and Kodak/X-Omat
      V radiographic film. Compared to other dosimeters, the ROF results for miniALA
      show differences of up to 3% for the smallest fields and 7% for the largest ones.
      These differences were within the miniALA experimental uncertainty (-5-6% at 1
      sigma). For BP measurements, the maximum penumbra width difference observed
      between miniALA and film (10%-90% width) was less than 1 mm for square fields and
      within 1-2 mm for circular fields. These penumbra width results indicate that the
      spatial resolution of the miniALA is comparable to that of radiographic film and
      its dimensions are adequate for the field sizes used in this experiment. The K
      Band EPR spectrometer provided adequate sensitivity for assessment of miniALAs
      with doses of the order of tens of Grays, making this dosimetry system (K
      Band/miniALA) a potential candidate for use in radiosurgery dosimetry.

PMID- 17555240
TI  - Water-equivalent dosimeter array for small-field external beam radiotherapy.
AB  - With the increasing complexity of dose patterns external beam radiotherapy, there
      is a great need for new types of dosimeters. We studied the first prototype of a
      new dosimeter array consisting of water-equivalent plastic scintillating fibers
      for dose measurement in external beam radiotherapy. We found that this array
      allows precise, rapid dose evaluation of small photon fields. Starting with a
      dosimeter system constructed with a single scintillating fiber coupled to a clear
      optical fiber and read using a charge coupled device camera, we looked at the
      dosimeter's spatial resolution under small radiation fields and angular
      dependence. Afterward, we analyzed the camera's light collection to determine the
      maximum array size that could be built. Finally, we developed a prototype made of
      ten scintillating fiber detectors to study the behavior and precision of this
      system in simple dosimetric situations. The scintillation detector showed no
      measurable angular dependence. Comparison of the scintillation detector and a
      small-volume ion chamber showed agreement except for 1 x 1 and 0.5 x 5.0 cm (2)
      fields where the output factor measured by the scintillator was higher. The
      actual field of view of the camera could accept more than 4000 scintillating
      fiber detectors simultaneously. Evaluation of the dose profile and depth dose
      curve using a prototype with ten scintillating fiber detectors showed precise,
      rapid dose evaluation even with placement of more than 75 optical fibers in the
      field to simulate what would happen in a larger array. We concluded that this
      scintillating fiber dosimeter array is a valuable tool for dose measurement in
      external beam radiotherapy. It possesses the qualities necessary to evaluate
      small and irregular fields with various incident angles such as those encountered
      in intensity-modulated radiotherapy, radiosurgery, and tomotherapy.

PMID- 17555241
TI  - Extension of the reconstruction field of view and truncation correction using
      sinogram decomposition.
AB  - We propose a novel truncation correction algorithm that completes unmeasured data
      outside of the scan field of view, which allows extending the reconstruction
      field of view. When a patient extends outside the detector coverage the
      projection data are transversely truncated, which causes severe artifacts. The
      proposed method utilizes the idea of sinogram decomposition, where we consider
      sinogram curves corresponding to image points outside the field of view. We
      propose two ways to estimate the truncated data, one based on the minimum value
      along the sinogram curve, and the other based on the data values near the edge of
      truncation. Both estimation methods are combined to achieve uniform image quality
      improvement from the edge of truncation to the outer side of the extended region.
      In our evaluation with simulated and real projection data we compare the proposed
      method with existing methods and investigate the dependence on the amount of
      truncation. The evaluation shows that the proposed method handles cases when
      truncation is present on both sides of the detector, or when a high-contrast
      object is located outside the field of view.

PMID- 17555242
TI  - An independent dose calculation algorithm for MLC-based stereotactic
      radiotherapy.
AB  - We have developed an algorithm to calculate dose in a homogeneous phantom for
      radiotherapy fields defined by multi-leaf collimator (MLC) for both static and
      dynamic MLC delivery. The algorithm was developed to supplement the dose
      algorithms of the commercial treatment planning systems (TPS). The motivation for
      this work is to provide an independent dose calculation primarily for quality
      assurance (QA) and secondarily for the development of static MLC field based
      inverse planning. The dose calculation utilizes a pencil-beam kernel. However, an
      explicit analytical integration results in a closed form for rectangular-shaped
      beamlets, defined by single leaf pairs. This approach reduces spatial integration
      to summation, and leads to a simple method of determination of model parameters.
      The total dose for any static or dynamic MLC field is obtained by summing over
      all individual rectangles from each segment which offers faster speed to
      calculate two-dimensional dose distributions at any depth in the phantom.
      Standard beam data used in the commissioning of the TPS was used as input data
      for the algorithm. The calculated results were compared with the TPS and
      measurements for static and dynamic MLC. The agreement was very good (<2.5%) for
      all tested cases except for very small static MLC sizes of 0.6 cm x 0.6 cm (<6%)
      and some ion chamber measurements in a high gradient region (<4.4%). This finding
      enables us to use the algorithm for routine QA as well as for research
      developments.

PMID- 17555243
TI  - The impact of temporal inaccuracies on 4DCT image quality.
AB  - Accurate delineation of target volumes is one of the critical components
      contributing to the success of image-guided radiotherapy treatments and several
      imaging modalities are employed to increase the accuracy in target
      identification. Four-dimensional (4D) techniques are incorporated into existing
      radiation imaging techniques like computed tomography (CT) to account for the
      mobility of the target volumes. However, these methods in some cases introduce
      further inaccuracies in the target delineation when further quality assurance
      measures are not implemented. A source of commonly observed inaccuracy is the
      misidentification of the respiration cycles and resulting respiration phase
      assignments used in the construction of the 4D patient model. The aim of this
      work is to emphasize the importance of optimal respiration phase assignment
      during the 4DCT image acquisition process and to perform a quantitative
      assessment of the effect of inaccurate phase assignments on the overall image
      quality. The accuracy of the phase assignment was assessed by comparison with an
      independent calculation of the respiration phases. Misplaced phase assignments
      manifest themselves as deformations and artifacts in reconstructed images. These
      effects are quantified as volumetric discrepancies in the localization of target
      objects represented by spherical phantoms. Measurements are performed using a
      fully programmable motion phantom designed and built at Mayo Clinic (Rochester,
      MN). Implementation of a case based independent check and correction procedure is
      also demonstrated with emphasis on the use of this procedure in the clinical
      environment. Review of clinical 4D scans performed in this institution showed
      discrepancies in the phase assignments in about 40% of the cases when compared to
      our independent calculations. It is concluded that for improved image
      reconstruction, an independent check of the sorting procedure should be performed
      for each clinical 4DCT case.

PMID- 17555244
TI  - Gamma Knife 3-D dose distribution near the area of tissue inhomogeneities by
      normoxic gel dosimetry.
AB  - The accuracy of the Leksell GammaPlan, the dose planning system of the Gamma
      Knife Model-B, was evaluated near tissue inhomogeneities, using the gel dosimetry
      method. The lack of electronic equilibrium around the small-diameter gamma beams
      can cause dose calculation errors in the neighborhood of an air-tissue interface.
      An experiment was designed to investigate the effects of inhomogeneity near the
      paranosal sinuses cavities. The homogeneous phantom was a spherical glass balloon
      of 16 cm diameter, filled with MAGIC gel; i.e., the normoxic polymer gel. Two
      hollow PVC balls of 2 cm radius, filled with N2 gas, represented the air cavities
      inside the inhomogeneous phantom. For dose calibration purposes, 100 ml gel
      containing vials were irradiated at predefined doses, and then scanned in a MR
      unit. Linearity was observed between the delivered dose and the reciprocal of the
      T2 relaxation time constant of the gel. Dose distributions are the results of a
      single shot of irradiation, obtained by collimating all 201 cobalt sources to a
      known target in the phantom. Both phantoms were irradiated at the same dose level
      at the same coordinates. Stereotactic frames and fiducial markers were attached
      to the phantoms prior to MR scanning. The dose distribution predicted by the
      Gamma Knife planning system was compared with that of the gel dosimetry. As
      expected, for the homogeneous phantom the isodose diameters measured by the gel
      dosimetry and the GammaPlan differed by 5% at most. However, with the
      inhomogeneous phantom, the dose maps in the axial, coronal and sagittal planes
      were spatially different. The diameters of the 50% isodose curves differed 43% in
      the X axis and 32% in the Y axis for the Z =90 mm axial plane; by 44% in the X
      axis and 24% in the Z axis for the Y=90 mm coronal plane; and by 32% in the Z
      axis and 42% in the Y axis for the X=92 mm sagittal plane. The lack of ability of
      the GammaPlan to predict the rapid dose fall off, due to the air cavities behind
      or near the lesion led to an overestimation of the dose that was actually
      delivered. Clinically, this can result in underdosing of lesions near tissue
      inhomogeneities in patients under treatment.

PMID- 17555245
TI  - Direct aperture optimization for online adaptive radiation therapy.
AB  - This paper is the first investigation of using direct aperture optimization (DAO)
      for online adaptive radiation therapy (ART). A geometrical model representing the
      anatomy of a typical prostate case was created. To simulate interfractional
      deformations, four different anatomical deformations were created by
      systematically deforming the original anatomy by various amounts (0.25, 0.50,
      0.75, and 1.00 cm). We describe a series of techniques where the original
      treatment plan was adapted in order to correct for the deterioration of dose
      distribution quality caused by the anatomical deformations. We found that the
      average time needed to adapt the original plan to arrive at a clinically
      acceptable plan is roughly half of the time needed for a complete plan
      regeneration, for all four anatomical deformations. Furthermore, through
      modification of the DAO algorithm the optimization search space was reduced and
      the plan adaptation was significantly accelerated. For the first anatomical
      deformation (0.25 cm), the plan adaptation was six times more efficient than the
      complete plan regeneration. For the 0.50 and 0.75 cm deformations, the
      optimization efficiency was increased by a factor of roughly 3 compared to the
      complete plan regeneration. However, for the anatomical deformation of 1.00 cm,
      the reduction of the optimization search space during plan adaptation did not
      result in any efficiency improvement over the original (nonmodified) plan
      adaptation. The anatomical deformation of 1.00 cm demonstrates the limit of this
      approach. We propose an innovative approach to online ART in which the plan
      adaptation and radiation delivery are merged together and performed concurrently
      adaptive radiation delivery (ARD). A fundamental advantage of ARD is the fact
      that radiation delivery can start almost immediately after image acquisition and
      evaluation. Most of the original plan adaptation is done during the radiation
      delivery, so the time spent adapting the original plan does not increase the
      overall time the patient has to spend on the treatment couch. As a consequence,
      the effective time allotted for plan adaptation is drastically reduced. For the
      0.25, 0.5, and 0.75 cm anatomical deformations, the treatment time was increased
      by only 2, 4, and 6 s, respectively, as compared to no plan adaptation. For the
      anatomical deformation of 1.0 cm the time increase was substantially larger. The
      anatomical deformation of 1.0 cm represents an extreme case, which is rarely
      observed for the prostate, and again demonstrates the limit of this approach. ARD
      shows great potential for an online adaptive method with minimal extension of
      treatment time.

PMID- 17555246
TI  - A fast algorithm for gamma evaluation in 3D.
AB  - The gamma-evaluation method is a tool by which dose distributions can be compared
      in a quantitative manner combining dose-difference and distance-to-agreement
      criteria. Since its introduction, the gamma evaluation has been used in many
      studies and is on the verge of becoming the preferred dose distribution
      comparison method, particularly for intensity-modulated radiation therapy (IMRT)
      verification. One major disadvantage, however, is its long computation time,
      which especially applies to the comparison of three-dimensional (3D) dose
      distributions. We present a fast algorithm for a full 3D gamma evaluation at high
      resolution. Both the reference and evaluated dose distributions are first
      resampled on the same grid. For each point of the reference dose distribution,
      the algorithm searches for the best point of agreement according to the gamma
      method in the evaluated dose distribution, which can be done at a subvoxel
      resolution. Speed, computer memory efficiency, and high spatial resolution are
      achieved by searching around each reference point with increasing distance in a
      sphere, which has a radius of a chosen maximum search distance and is
      interpolated "on-the-fly" at a chosen sample step size. The smaller the sample
      step size and the larger the differences between the dose distributions, the
      longer the gamma evaluation takes. With decreasing sample step size, statistical
      measures of the 3D gamma distribution converge. Two clinical examples were
      investigated using 3% of the prescribed dose as dose-difference and 0.3 cm as
      distance-to-agreement criteria. For 0.2 cm grid spacing, the change in gamma
      indices was negligible below a sample step size of 0.02 cm. Comparing the full 3D
      gamma evaluation and slice-by-slice 2D gamma evaluations ("2.5D") for these
      clinical examples, the gamma indices improved by searching in full 3D space, with
      the average gamma index decreasing by at least 8%.

PMID- 17555247
TI  - Adaptive deformable model for colonic polyp segmentation and measurement on CT
      colonography.
AB  - Polyp size is one important biomarker for the malignancy risk of a polyp. This
      paper presents an improved approach for colonic polyp segmentation and
      measurement on CT colonography images. The method is based on a combination of
      knowledge-guided intensity adjustment, fuzzy clustering, and adaptive deformable
      model. Since polyps on haustral folds are the most difficult to be segmented, we
      propose a dual-distance algorithm to first identify voxels on the folds, and then
      introduce a counter-force to control the model evolution. We derive linear and
      volumetric measurements from the segmentation. The experiment was conducted on
      395 patients with 83 polyps, of which 43 polyps were on haustral folds. The
      results were validated against manual measurement from the optical colonoscopy
      and the CT colonography. The paired t-test showed no significant difference, and
      the R(2) correlation was 0.61 for the linear measurement and 0.98 for the
      volumetric measurement. The mean Dice coefficient for volume overlap between
      automatic and manual segmentation was 0.752 (standard deviation 0.154).

PMID- 17555248
TI  - Monte carlo evaluation of the AAA treatment planning algorithm in a heterogeneous
      multilayer phantom and IMRT clinical treatments for an Elekta SL25 linear
      accelerator.
AB  - The Anisotropic Analytical Algorithm (AAA) is a new pencil beam
      convolution/superposition algorithm proposed by Varian for photon dose
      calculations. The configuration of AAA depends on linear accelerator design and
      specifications. The purpose of this study was to investigate the accuracy of AAA
      for an Elekta SL25 linear accelerator for small fields and intensity modulated
      radiation therapy (IMRT) treatments in inhomogeneous media. The accuracy of AAA
      was evaluated in two studies. First, AAA was compared both with Monte Carlo (MC)
      and the measurements in an inhomogeneous phantom simulating lung equivalent
      tissues and bone ribs. The algorithm was tested under lateral electronic
      disequilibrium conditions, using small fields (2 x 2 cm(2)). Good agreement was
      generally achieved for depth dose and profiles, with deviations generally below
      3% in lung inhomogeneities and below 5% at interfaces. However, the effects of
      attenuation and scattering close to the bone ribs were not fully taken into
      account by AAA, and small inhomogeneities may lead to planning errors. Second,
      AAA and MC were compared for IMRT plans in clinical conditions, i.e., dose
      calculations in a computed tomography scan of a patient. One ethmoid tumor, one
      orophaxynx and two lung tumors are presented in this paper. Small differences
      were found between the dose volume histograms. For instance, a 1.7% difference
      for the mean planning target volume dose was obtained for the ethmoid case. Since
      better agreement was achieved for the same plans but in homogeneous conditions,
      these differences must be attributed to the handling of inhomogeneities by AAA.
      Therefore, inherent assumptions of the algorithm, principally the assumption of
      independent depth and lateral directions in the scaling of the kernels, were
      slightly influencing AAA's validity in inhomogeneities. However, AAA showed a
      good accuracy overall and a great ability to handle small fields in inhomogeneous
      media compared to other pencil beam convolution algorithms.

PMID- 17555249
TI  - Film dosimetry calibration method for pulsed-dose-rate brachytherapy with an
      192Ir source.
AB  - 192Ir sources have been widely used in clinical brachytherapy. An important
      challenge is to perform dosimetric measurements close to the source despite the
      steep dose gradient. The common, inexpensive silver halide film is a classic two
      dimensional integrator dosimeter and would be an attractive solution for these
      dose measurements. The main disadvantage of film dosimetry is the film response
      to the low-energy photon. Since the photon energy spectrum is known to vary with
      depth, the sensitometric curves are expected to be dependent on depth. The
      purpose of this study is to suggest a correction method for silver halide film
      dosimetry that overcomes the response changes at different depths. Sensitometric
      curves have been obtained at different depths with verification film near a 1 Ci
      192Ir pulsed-dose-rate source. The depth dependence of the film response was
      observed and a correction function was established. The suitability of the method
      was tested through measurement of the radial dose profile and radial dose
      function. The results were compared to Monte Carlo-simulated values according to
      the TG43 formalism. Monte Carlo simulations were performed separately for the
      beta and gamma source emissions, using the EGS4 code system, including the low
      energy photon and electron transport optimization procedures. The beta source
      emission simulation showed that the beta dose contribution could be neglected and
      therefore the film-depth dependence could not be attributed to this part of the
      source radioactivity. The gamma source emission simulations included photon
      spectra collection at several depths. The results showed a depth-dependent
      softening of the photon spectrum that can explain the film-energy dependence.

PMID- 17555250
TI  - Maximum likelihood estimation of proton irradiated field and deposited dose
      distribution.
AB  - In proton therapy, it is important to evaluate the field irradiated with protons
      and the deposited dose distribution in a patient's body. Positron emitters
      generated through fragmentation reactions of target nuclei can be used for this
      purpose. By detecting the annihilation gamma rays from the positron emitters, the
      annihilation gamma ray distribution can be obtained which has information about
      the quantities essential to proton therapy. In this study, we performed
      irradiation experiments with mono-energetic proton beams of 160 MeV and the
      spread-out Bragg peak beams to three kinds of targets. The annihilation events
      were detected with a positron camera for 500 s after the irradiation and the
      annihilation gamma ray distributions were obtained. In order to evaluate the
      range and the position of distal and proximal edges of the SOBP, the maximum
      likelihood estimation (MLE) method was applied to the detected distributions. The
      evaluated values with the MLE method were compared with those estimated from the
      measured dose distributions. As a result, the ranges were determined with the
      difference between the MLE range and the experimental range less than 1.0 mm for
      all targets. For the SOBP beams, the positions of distal edges were determined
      with the difference less than 1.0 mm. On the other hand, the difference amounted
      to 7.9 mm for proximal edges.

PMID- 17555251
TI  - Validity of model approximations for receptor-ligand kinetics in nuclear
      medicine.
AB  - An appropriate mathematical model is required for quantitative analysis of high
      affinity radioligands as direct or surrogate probes to measure receptor
      distribution, affinity, concentration, binding potential, and endogenous or
      exogenous ligand occupancy levels. For studies with positron emission tomography
      (PET) or single photon emission computed tomography (SPECT), the receptor-ligand
      compartment model has been well established and widely used. This pharmacokinetic
      model is represented mathematically by a set of nonlinear ordinary differential
      equations. Variations of models for PET and SPECT account for radioactive decay
      differently. These are not equivalent and entail assumptions or approximations
      that may be not appreciated. In this study, a general form of the model is
      presented and compared with others with various approximations, which are valid
      only under specific conditions. The various approximate formulations were
      analytically compared to the exact model to identify the terms that were
      neglected in the approximate formulations. The extent to which the approximations
      impact the model solutions was assessed by computer simulations based on
      numerical solutions to each set of equations. Specifically, each model
      formulation was tested using three simulated injection protocols representing a
      typical PET experiment, a typical SPECT experiment, and an extreme experiment
      where both the injected activity and the specific activity were very high. No
      significant differences were found among the output of the three model
      formulations when the PET and SPECT injection protocols were tested. The only
      conditions that produced significant differences occurred when the specific
      activity and the administered activity were simultaneously very high. These
      conditions, however, have little practical relevance to experimentally achievable
      conditions due to radiation dose and specific activity of radiopharmaceuticals

PMID- 17555252
TI  - Energy dependence of commercially available diode detectors for in-vivo
      dosimetry.
AB  - The energy dependence of commercially available diode detectors was measured for
      nominal accelerating potential ranging between Co-60 and 17 MV. The measurements
      were performed in a liquid water phantom at 5 cm depth for 10 x 10 cm2 collimator
      setting and source-to-detector distance of 100 cm. The response (nC/Gy) was
      normalized to Co-60 beam after corrections for the dose rate and temperature
      dependences for each diode. The energy dependence, calculated by taking the
      percent difference between the maximum and minimum sensitivity normalized to Co
      60 beam, varied by 39% for the n-type Isorad Red, 26% for the n-type Isorad
      Electron, 19% for the QED Red (p-type), 15% for the QED Electron (p-type), 11%
      for the QED Blue (p-type), and 6% for the EDP10 diode for nominal accelerating
      potential between Co-60 and 17 MV. It varied by 34% for the Isorad-3 Gold #1 and
      #2, 35% for the Veridose Green, 15% for the Veridose Yellow, 9% for the Veridose
      Electron, 21% for the n-type QED Gold, 24% for the n-type QED Red, 3% for the
      EDP23G, 2% for the PFD (photon field detector), 7% for the EDP103G, and 16% for
      the EDP203G for nominal accelerating potential between Co-60 and 15 MV. The
      magnitude of the energy dependence is verified by Monte Carlo simulation. We
      concluded that the energy dependence does not depend on whether the diode is n-
      or p-type but rather depends mainly on the material around the die such as the
      buildup and the geometry of the buildup material. As a result, the value of the
      energy dependence can vary for each individual diode depending on the actual
      geometry and should be used with caution.

PMID- 17555253
TI  - Novel ultrahigh resolution data acquisition and image reconstruction for multi
      detector row CT.
AB  - We present and evaluate a special ultrahigh resolution mode providing
      considerably enhanced spatial resolution both in the scan plane and in the z-axis
      direction for a routine medical multi-detector row computed tomography (CT)
      system. Data acquisition is performed by using a flying focal spot both in the
      scan plane and in the z-axis direction in combination with tantalum grids that
      are inserted in front of the multi-row detector to reduce the aperture of the
      detector elements both in-plane and in the z-axis direction. The dose utilization
      of the system for standard applications is not affected, since the grids are
      moved into place only when needed and are removed for standard scanning. By means
      of this technique, image slices with a nominal section width of 0.4 mm (measured
      full width at half maximum=0.45 mm) can be reconstructed in spiral mode on a CT
      system with a detector configuration of 32 x 0.6 mm. The measured 2% value of the
      in-plane modulation transfer function (MTF) is 20.4 lp/cm, the measured 2% value
      of the longitudinal (z axis) MTF is 21.5 lp/cm. In a resolution phantom with
      metal line pair test patterns, spatial resolution of 20 lp/cm can be demonstrated
      both in the scan plane and along the z axis. This corresponds to an object size
      of 0.25 mm that can be resolved. The new mode is intended for ultrahigh
      resolution bone imaging, in particular for wrists, joints, and inner ear studies,
      where a higher level of image noise due to the reduced aperture is an acceptable
      trade-off for the clinical benefit brought about by the improved spatial
      resolution.

PMID- 17555254
TI  - Monte Carlo study on the imaging performance of powder Lu2SiO5:Ce phosphor
      screens under x-ray excitation: comparison with Gd2O2S:Tb screens.
AB  - Lu2SiO5: Ce (LSO) scintillator is a relatively new luminescent material which has
      been successfully applied in positron emission tomography systems. Since it has
      been recently commercially available in powder form, it could be of value to
      investigate its performance for use in x-ray projection imaging as both physical
      and scintillating properties indicate a promising material for such applications.
      In the present study, a custom and validated Monte Carlo simulation code was used
      in order to examine the performance of LSO, under diagnostic radiology
      (mammography and general radiography) conditions. The Monte Carlo code was based
      on a model using Mie scattering theory for the description of light attenuation.
      Imaging characteristics, related to image brightness, spatial resolution and
      noise of LSO screens were predicted using only physical parameters of the
      phosphor. The overall performance of LSO powder phosphor screens was investigated
      in terms of the: (i) quantum detection efficiency (ii) emitted K-characteristic
      radiation (iii) luminescence efficiency (iv) modulation transfer function (v)
      Swank factor and (vi) zero-frequency detective quantum efficiency [DQE(0)].
      Results were compared to the traditional rare-earth Gd2O2S:Tb (GOS) phosphor
      material. The relative luminescence efficiency of LSO phosphor was found inferior
      to that of GOS. This is due to the lower intrinsic conversion efficiency of LSO
      (0.08 instead of 0.15 of GOS) and the relatively high light extinction
      coefficient mext of this phosphor (0.239 mircom(-1) instead of 0.218 /microm(-1)
      for GOS). However, the property of increased light extinction combined with the
      rather sharp angular distribution of scattered light photons (anisotropy factor
      g=0.624 for LSO instead of 0.494 for GOS) reduce lateral light spreading and
      improve spatial resolution. In addition, LSO screens were found to exhibit better
      x-ray absorption as well as higher signal to noise transfer properties in the
      energy range from 18 keV up to 50.2 keV (e.g. DQE(0)=0.62 at 18 keV and for 34
      mg/cm2, instead of 0.58 for GOS). The results indicate that certain optical
      properties of LSO (optical extinction coefficient, scattering anisotropy factor)
      combined with the relatively high x-ray coefficients, make this material a
      promising phosphor which, under appropriate conditions, could be considered for
      use in x-ray projection imaging detectors.

PMID- 17555255
TI  - Monte Carlo study of si diode response in electron beams.
AB  - Silicon semiconductor diodes measure almost the same depth-dose distributions in
      both photon and electron beams as those measured by ion chambers. A recent study
      in ion chamber dosimetry has suggested that the wall correction factor for a
      parallel-plate ion chamber in electron beams changes with depth by as much as 6%.
      To investigate diode detector response with respect to depth, a silicon diode
      model is constructed and the water/silicon dose ratio at various depths in
      electron beams is calculated using EGSnrc. The results indicate that, for this
      particular diode model, the diode response per unit water dose (or water/diode
      dose ratio) in both 6 and 18 MeV electron beams is flat within 2% versus depth,
      from near the phantom surface to the depth of R50 (with calculation uncertainty
      <0.3%). This suggests that there must be some other correction factors for ion
      chambers that counter-balance the large wall correction factor at depth in
      electron beams. In addition, the beam quality and field-size dependence of the
      diode model are also calculated. The results show that the water/diode dose ratio
      remains constant within 2% over the electron energy range from 6 to 18 MeV. The
      water/diode dose ratio does not depend on field size as long as the incident
      electron beam is broad and the electron energy is high. However, for a very small
      beam size (1 X 1 cm(2)) and low electron energy (6 MeV), the water/diode dose
      ratio may decrease by more than 2% compared to that of a broad beam.

PMID- 17555256
TI  - A new Gamma Knife radiosurgery paradigm: tomosurgery.
AB  - This study proposes and simulates an inverse treatment planning and a continuous
      dose delivery approach for the Leksell Gamma Knife (LGK, Elekta, Stockholm,
      Sweden) which we refer to as "Tomosurgery." Tomosurgery uses an isocenter that
      moves within the irradiation field to continuously deliver the prescribed
      radiation dose in a raster-scanning format, slice by slice, within an
      intracranial lesion. Our Tomosurgery automated (inverse) treatment planning
      algorithm utilizes a two-stage optimization strategy. The first stage reduces the
      current three-dimensional (3D) treatment planning problem to a series of more
      easily solved 2D treatment planning subproblems. In the second stage, those 2D
      treatment plans are assembled to obtain a final 3D treatment plan for the entire
      lesion. We created Tomosurgery treatment plans for 11 patients who had already
      received manually-generated LGK treatment plans to treat brain tumors. For the
      seven cases without critical structures (CS), the Tomosurgery treatment plans
      showed borderline to significant improvement in within-tumor dose standard
      deviation (STD) (p <0.058, or p <0.011 excluding case 2) and conformality (p <
      0.042), respectively. In three of the four cases that presented CS, the
      Tomosurgery treatment plans showed no statistically significant improvements in
      dose conformality (p <0.184), and borderline significance in improving within
      tumor dose homogeneity (p <0.054); CS damage measured by V20 or V30 (i.e.,
      irradiated CS volume that receives > or =20% or > or =30% of the maximum dose)
      showed no significant improvement in the Tomosurgery treatment plans (p<0.345 and
      p <0.423, respectively). However, the overall CS dose volume histograms were
      improved in the Tomosurgery treatment plans. In addition, the LGK Tomosurgery
      inverse treatment planning required less time than standard of care, forward
      (manual) LGK treatment planning (i.e., 5-35 min vs 1-3 h) for all 11 cases. We
      expect that LGK Tomosurgery will speed treatment planning and improve treatment
      quality, especially for large and/or geometrically complex lesions. However,
      using only 4 mm collimators could greatly increase treatment plan delivery time
      for a large brain lesion. This issue is subject to further investigation.

PMID- 17555257
TI  - In vivo dosimeters for HDR brachytherapy: a comparison of a diamond detector,
      MOSFET, TLD, and scintillation detector.
AB  - The large dose gradients in brachytherapy necessitate a detector with a small
      active volume for accurate dosimetry. The dosimetric performance of a novel
      scintillation detector (BrachyFOD) is evaluated and compared to three
      commercially available detectors, a diamond detector, a MOSFET, and LiF TLDs. An
      192Ir HDR brachytherapy source is used to measure the depth dependence, angular
      dependence, and temperature dependence of the detectors. Of the commercially
      available detectors, the diamond detector was found to be the most accurate, but
      has a large physical size. The TLDs cannot provide real time readings and have
      depth dependent sensitivity. The MOSFET used in this study was accurate to within
      5% for distances of 20 to 50 mm from the 192Ir source in water but gave errors of
      30%-40% for distances greater than 50 mm from the source. The BrachyFOD was found
      to be accurate to within 3% for distances of 10 to 100 mm from an HDR 192Ir
      brachytherapy source in water. It has an angular dependence of less than 2% and
      the background signal created by Cerenkov radiation and fluorescence of the
      plastic optical fiber is insignificant compared to the signal generated in the
      scintillator. Of the four detectors compared in this study the BrachyFOD has the
      most favorable combination of characteristics for dosimetry in HDR brachytherapy.

PMID- 17555258
TI  - An investigation of temporal regularization techniques for dynamic PET
      reconstructions using temporal splines.
AB  - The use of a temporal B-spline basis for the reconstruction of dynamic positron
      emission tomography data was investigated. Maximum likelihood (ML)
      reconstructions using an expectation maximization framework and maximum A
      posteriori (MAP) reconstructions using the generalized expectation maximization
      framework were evaluated. Different parameters of the B-spline basis of such as
      order, number of basis functions and knot placing were investigated in a
      reconstruction task using simulated dynamic list-mode data. We found that a
      higher order basis reduced both the bias and variance. Using a higher number of
      basis functions in the modeling of the time activity curves (TACs) allowed the
      algorithm to model faster changes of the TACs, however, the TACs became noisier.
      We have compared ML, Gaussian postsmoothed ML and MAP reconstructions. The noise
      level in the ML reconstructions was controlled by varying the number of basis
      functions. The MAP algorithm penalized the integrated squared curvature of the
      reconstructed TAC. The postsmoothed ML was always outperformed in terms of bias
      and variance properties by the MAP and ML reconstructions. A simple adaptive knot
      placing strategy was also developed and evaluated. It is based on an arc length
      redistribution scheme during the reconstruction. The free knot reconstruction
      allowed a more accurate reconstruction while reducing the noise level especially
      for fast changing TACs such as blood input functions. Limiting the number of
      temporal basis functions combined with the adaptive knot placing strategy is in
      this case advantageous for regularization purposes when compared to the other
      regularization techniques.

PMID- 17555259
TI  - Segmentation and leaf sequencing for intensity modulated arc therapy.
AB  - A common method in generating intensity modulated radiation therapy (IMRT) plans
      consists of a three step process: an optimized fluence intensity map (IM) for
      each beam is generated via inverse planning, this IM is then segmented into
      discrete levels, and finally, the segmented map is translated into a set of MLC
      apertures via a leaf sequencing algorithm. To date, limited work has been done on
      this approach as it pertains to intensity modulated arc therapy (IMAT),
      specifically in regards to the latter two steps. There are two determining
      factors that separate IMAT segmentation and leaf sequencing from their IMRT
      equivalents: (1) the intrinsic 3D nature of the intensity maps (standard 2D maps
      plus the angular component), and (2) that the dynamic multileaf collimator (MLC)
      constraints be met using a minimum number of arcs. In this work, we illustrate a
      technique to create an IMAT plan that replicates Tomotherapy deliveries by
      applying IMAT specific segmentation and leaf-sequencing algorithms to Tomotherapy
      output sinograms. We propose and compare two alternative segmentation techniques,
      a clustering method, and a bottom-up segmentation method (BUS). We also introduce
      a novel IMAT leaf-sequencing algorithm that explicitly takes leaf movement
      constraints into consideration. These algorithms were tested with 51 angular
      projections of the output leaf-open sinograms generated on the Hi-ART II
      treatment planning system (Tomotherapy Inc.). We present two geometric phantoms
      and 2 clinical scenarios as sample test cases. In each case 12 IMAT plans were
      created, ranging from 2 to 7 intensity levels. Half were generated using the BUS
      segmentation and half with the clustering method. We report on the number of arcs
      produced as well as differences between Tomotherapy output sinograms and
      segmented IMAT intensity maps. For each case one plan for each segmentation
      method is chosen for full Monte Carlo dose calculation (NumeriX LLC) and dose
      volume histograms (DVH) are calculated. In all cases, the BUS method outperformed
      the clustering, method. We recommend using the BUS algorithm and discuss
      potential improvements to the clustering algorithms.

PMID- 17555260
TI  - Effect of the first day correction on systematic setup error reduction.
AB  - Treatment simulation is usually performed with a conventional simulator using kV
      X-rays or with a computed tomography (CT) simulator before the treatment course
      begins. The purpose is to verify patient setup under the same conditions as for
      treatment planning. Systematic (preparation) setup errors can be introduced by
      this process. The purpose of this study is to characterize the setup errors using
      electronic portal image (EPI) analyses and to propose a method to reduce the
      systematic component by performing simulation and patient preparation on the
      treatment machine. In this study, the first four or five days EPIs were analyzed
      from a total of 533 prostate cancer patients who were simulated on conventional
      simulators. We characterized setup errors using four parameters: {M(microi),
      Sigma (microi), RMS(microi), sigma (sigmai)}, where microi and sigmai are
      individual patient mean and standard deviation, M, Sigma, and RMS are the mean,
      standard deviation, and root-mean-square of underlying variables (microi and
      sigmai). We have performed a simulation of removing systematic components by
      correcting the first day setup error. As a comparison, we also carried out a
      similar analyses for patients simulated on a CT simulator and patients treated on
      a linac with an on-board kV CT imaging system, although a limited number of
      patients were available in these two samples. We found that Sigma
      (/ui)=(2.6,3.4,2.4) mm, and RMS(sigmai)=(1.5,1.9,1.0) mm in lateral,
      anterior/posterior, and cranial/caudal directions, indicating that systematic
      errors are much larger than random errors. Strong correlations were found between
      measurement on the first day and microi, implying the first day's measurement is
      a good predictor for microi. The same parameters were also computed for days 2-4,
      with and without the first day correction. Without correction, M(microi)2
      4=(0.7,1.6,-1.0) mm, and Sigma(microi)2-4=(2.6,3.5,2.4) mm. With correction,
      M(microi)2-4=(0.0,0.4,0.4) mm, much closer to zero, and Sigma(microi)2
      4=(1.8,2.2, 1.2) mm, also much smaller. While the use of a CT simulator can
      reduce the systematic errors, the benefits of first day correction can still be
      observed, although at a smaller magnitude. Therefore, the systematic setup error
      can be significantly reduced if the patient is marked and fields are verified on
      the treatment machine on the first fraction, preferably with an on-board kV
      imaging system.

PMID- 17555261
TI  - Development of an ultrasmall C-band linear accelerator guide for a four
      dimensional image-guided radiotherapy system with a gimbaled x-ray head.
AB  - We are developing a four-dimensional image-guided radiotherapy system with a
      gimbaled x-ray head. It is capable of pursuing irradiation and delivering
      irradiation precisely with the help of an agile moving x-ray head on the gimbals.
      Requirements for the accelerator guide were established, system design was
      developed, and detailed design was conducted. An accelerator guide was
      manufactured and basic beam performance and leakage radiation from the
      accelerator guide were evaluated at a low pulse repetition rate. The accelerator
      guide including the electron gun is 38 cm long and weighs about 10 kg. The length
      of the accelerating structure is 24.4 cm. The accelerating structure is a
      standing wave type and is composed of the axial-coupled injector section and the
      side-coupled acceleration cavity section. The injector section is composed of one
      prebuncher cavity, one buncher cavity, one side-coupled half cavity, and two
      axial coupling cavities. The acceleration cavity section is composed of eight
      side-coupled nose reentrant cavities and eight coupling cavities. The electron
      gun is a diode-type gun with a cerium hexaboride (CeB6) direct heating cathode.
      The accelerator guide can be operated without any magnetic focusing device.
      Output beam current was 75 mA with a transmission efficiency of 58%, and the
      average energy was 5.24 MeV. Beam energy was distributed from 4.95 to 5.6 MeV.
      The beam profile, measured 88 mm from the beam output hole on the axis of the
      accelerator guide, was 0.7 mm X 0.9 mm full width at half maximum (FWHM) width.
      The beam loading line was 5.925 (MeV)-Ib (mA) X 0.00808 (MeV/mA), where Ib is
      output beam current. The maximum radiation leakage of the accelerator guide at
      100 cm from the axis of the accelerator guide was calculated as 0.33 cGy/min at
      the rated x-ray output of 500 cGy/min from the measured value. This leakage
      requires no radiation shielding for the accelerator guide itself per IEC 60601-2
      1.

PMID- 17555262
TI  - Dose calculation validation of Vmc++ for photon beams.
AB  - The radiation therapy specific Voxel Monte Carlo (VMC+ +) dose calculation
      algorithm achieves a dramatic improvement in MC dose calculation efficiency for
      radiation therapy treatment planning dose evaluation compared with other MC
      algorithms. This work aims to validate VMC+ + for radiation therapy photon beam
      planning. VMC++ was validated with respect to the well-benchmarked EGS-based
      DOSXYZnrc by comparing depth dose and lateral profiles for field sizes ranging
      from 1 X 1 to 40 x 40 cm(2) for 6 and 18 MV beams in a homogeneous water phantom
      and in a simulated bone-lung-bone phantom. Patient treatment plan dose
      distributions were compared for five prostate plans and five head-and-neck (H/N)
      plans, all using intensity-modulated radiotherapy beams. For all tests, the same
      incident particles were used in both codes to isolate differences due to modeling
      of the radiation source. Voxel-by-voxel observed differences were analyzed to
      distinguish between systematic and purely statistical differences. Dose-volume
      histogram-derived dose indices were compared for the patient plans. For the
      homogeneous water phantom and the bone-lung-bone phantom, the depth dose curve
      predicted by VMC+ + agreed with that predicted by DOSXYZnrc within expected
      statistical uncertainty in all voxels except the surface voxel of the water
      phantom, where VMC+ + predicted a lower dose. When the electron cutoff parameter
      was decreased for both codes, the surface voxel agreed within expected
      statistical uncertainty. For prostate plans, the most severe difference between
      the codes resulted in 55% of the voxels showing a systematic difference of 0.32%
      of maximum dose. For H/N plans, the largest difference observed resulted in 2% of
      the voxels showing a systematic difference of 0.98% of maximum dose. For the
      prostate plans, the most severe difference in the planning target volume D95 was
      0.4%, the rectum D35 was 0.2%, the rectum DI7 was 0.2%, the bladder D50 was 0.3%
      and the bladder D25 was 0.3%. For the H/N plans, the most severe difference in
      the gross tumor volume D98 was 0.4%, the clinical target volume D90 was 0.2%, the
      nodes D90 was 0.2%, the parotids D95 was 0.8%, and the cord D2 was 0.8%. All of
      these differences are clinically insignificant. VMC++ showed an average
      efficiency gain over DOSXYZnrc of at least an order of magnitude without
      introducing significant systematic bias. VMC + + can be used for photon beam MC
      patient dose computations without a clinically significant loss in accuracy.

PMID- 17555263
TI  - Patient dose considerations for routine megavoltage cone-beam CT imaging.
AB  - Megavoltage cone-beam CT (MVCBCT), the recent addition to the family of in-room
      CT imaging systems for image-guided radiation therapy (IGRT), uses a conventional
      treatment unit equipped with a flat panel detector to obtain a three-dimensional
      representation of the patient in treatment position. MVCBCT has been used for
      more than two years in our clinic for anatomy verification and to improve patient
      alignment prior to dose delivery. The objective of this research is to evaluate
      the image acquisition dose delivered to patients for MVCBCT and to develop a
      simple method to reduce the additional dose resulting from routine MVCBCT
      imaging. Conventional CT scans of phantoms and patients were imported into a
      commercial treatment planning system (TPS: Phillips, Pinnacle) and an arc
      treatment mimicking the MVCBCT acquisition process was generated to compute the
      delivered acquisition dose. To validate the dose obtained from the TPS, a simple
      water-equivalent cylindrical phantom with spaces for MOSFETs and an ion chamber
      was used to measure the MVCBCT image acquisition dose. Absolute dose
      distributions were obtained by simulating MVCBCTs of 9 and 5 monitor units (MU)
      on pelvis and head and neck patients, respectively. A compensation factor was
      introduced to generate composite plans of treatment and MVCBCT imaging dose. The
      article provides a simple equation to compute the compensation factor. The
      developed imaging compensation method was tested on routinely used clinical plans
      for prostate and head and neck patients. The quantitative comparison between the
      calculated dose by the TPS and measurement points on the cylindrical phantom were
      all within 3%. The dose percentage difference for the ion chamber placed in the
      center of the phantom was only 0.2%. For a typical MVCBCT, the dose delivered to
      patients forms a small anterior-posterior gradient ranging from 0.6 to 1.2 cGy
      per MVCBCT MU. MVCBCT acquisitions in the pelvis and head and neck areas deliver
      slightly more dose than current portal imaging but render soft tissue information
      for positioning. Overall, the additional dose from daily 9 MU MVCBCTs of prostate
      patients is small compared to the treatment dose (<4%). Dose-volume histograms of
      compensated plans for pelvis and head and neck patients imaged daily with MVCBCT
      showed no additional dose to the target and small increases at low doses. The
      results indicate that the dose delivered for MVCBCT imaging can be precisely
      calculated in the TPS and therefore included in the treatment plan. This allows
      simple plan compensations, such as slightly reducing the treatment dose, to
      minimize the total dose received by critical structures from daily positioning
      with MVCBCT. The proposed compensation factor reduces the number of MU per
      treatment beam per fraction. Both the number of fractions and the beam
      arrangement are kept unchanged. Reducing the imaging volume in the cranio-caudal
      direction can further reduce the dose delivered for MVCBCT. This is a useful
      feature to eliminate the imaging dose to the eyes or to focus on a specific
      region of interest for alignment.

PMID- 17555264
TI  - Influence of laser parameters on selective retinal treatment using single-phase
      heat transfer analyses.
AB  - Selective thermal treatment to retina is induced by short pulsed lasers to
      denaturize retinal pigment epithelium (RPE) selectively, while sparing the
      sensitive photoreceptors. The problem associated with the usage of short pulsed
      laser is the difficulty in determining the correct dosimetry parameters. This
      study quantifies the influence of laser parameters over the therapeutic range.
      The laser-tissue interaction is numerically investigated by analyzing the
      transient temperature in ocular tissues during the treatment. The rate process
      analysis for thermal injury is employed to estimate the selective damage of
      retina. The contours of Arrhenius integral value (Omeg/ Omegamax) presented in
      this study show both the area and magnitude of damage caused by various laser
      parameters. Results reveal that the 2 micros pulsed laser with green wavelength
      and Gaussian profile is relatively more effective for selective retinal
      treatment. The repetition frequency of 100 Hz is found to produce selectively RPE
      damage, while higher frequencies produce collateral damage to neural retina and
      choroid located within 2 microm from the RPE interface.

PMID- 17555265
TI  - Integral test phantom for dosimetric quality assurance of image guided and
      intensity modulated stereotactic radiotherapy.
AB  - The objective of this work is to develop a dosimetric phantom quality assurance
      (QA) of linear accelerators capable of cone-beam CT (CBCT) image guided and
      intensity-modulated radiotherapy (IG-IMRT). This phantom is to be used in an
      integral test to quantify in real-time both the performance of the image guidance
      and the dose delivery systems in terms of dose localization. The prototype IG
      IMRT QA phantom consisted of a cylindrical imaging phantom (CatPhan) combined
      with an array of 11 radiation diodes mounted on a 10 cm diameter disk, oriented
      perpendicular to the phantom axis. Basic diode response characterization was
      performed for 6 and 18 MV photons. The diode response was compared to planning
      system calculations in the open and penumbrae regions of simple and complex beam
      arrangements. The clinical use of the QA phantom was illustrated in an integral
      test of an IG-IMRT treatment designed for a clinical spinal radiosurgery case.
      The sensitivity of the phantom to multileaf collimator (MLC) calibration and
      setup errors in the clinical setting was assessed by introducing errors in the
      IMRT plan or by displacing the phantom. The diodes offered good response
      linearity and long-term reproducibility for both 6 and 18 MV. Axial dosimetry of
      coplanar beams (in a plane containing the beam axes) was made possible with the
      nearly isoplanatic response of the diodes over 360 degrees of gantry (usually
      within +/-1%). For single beam geometry, errors in phantom placement as small as
      0.5 mm could be accurately detected (in gradient > or = 1% /mm). In clinical
      setting, MLC systematic errors of 1 mm on a single MLC bank introduced in the
      IMRT plan were easily detectable with the QA phantom. The QA phantom demonstrated
      also sufficient sensitivity for the detection of setup errors as small as 1 mm
      for the IMRT delivery. These results demonstrated that the prototype can
      accurately and efficiently verify the entire IG-IMRT process. This tool, in
      conjunction with image guidance capabilities has the potential to streamline this
      QA process and improve the level of performance of image guided and intensity
      modulated radiotherapy.

PMID- 17555266
TI  - Accuracy of two heterogeneity dose calculation algorithms for IMRT in treatment
      plans designed using an anthropomorphic thorax phantom.
AB  - With the advent of intensity-modulated radiation therapy (IMRT), the inclusion of
      heterogeneity corrections is further complicated by the conformal delivery of
      many small beams forming steep dose gradients. Radiation treatment planning has
      evolved to take into account even small changes in tissue density so that the
      dose to tumor can be further optimized. However, different treatment planning
      systems incorporate different heterogeneity correction algorithms, and it is
      unclear whether any of these algorithms are superior to others in terms of
      accurately predicting delivered radiation doses relative to measurement in a
      clinical setting. The purpose of this study was to determine the accuracy of
      heterogeneity dose calculations from two widely used IMRT treatment planning
      systems (Pinnacle and Corvus) against measurement. These two systems handle
      heterogeneity dose corrections by means of a collapsed-cone convolution
      superposition algorithm and a finite-size pencil-beam algorithm with one
      dimensional depth scaling correction, respectively. Treatment plans were
      generated by each system using an anthropomorphic thorax phantom, routine
      clinical lung tumor constraints, and a common prescribed dose. Dose measurements
      made by thermoluminescent detectors (TLDs) and radiochromic film positioned
      within the phantom's lung and offset tumor insert were then compared with the
      calculated values. The collapsed cone convolution superposition dose calculation
      algorithm provided clinically acceptable results (+/-5% of the normalization dose
      or 3 mm distance to agreement) in the designed treatment plan and delivery. The
      pencil-beam algorithm with an effective pathlength correction showed reasonable
      agreement within the gross tumor volume, overestimated dose within a majority of
      the planning target volume, and underestimated the extent of the penumbral
      broadening, yielding only about 60% accuracy when judged by the above criterion.
      Even judged by a more generous criterion (+/-7% /7 mm), the results were
      clinically unfavorable (at only about 80% accuracy). To ascertain the dose in
      heterogeneous regions such as the tumor-lung interface and the peripheral lung
      dose near the tumor, the superposition convolution algorithm that accounts for
      lateral scatter and electron transport should be used. The use of the pencil-beam
      algorithm with only an effective pathlength correction may result in the dose to
      the target being overestimated. As a result, a full understanding of any
      treatment planning system's heterogeneity algorithm is required prior to clinical
      implementation.

PMID- 17555267
TI  - Organ and effective doses in pediatric patients undergoing helical multislice
      computed tomography examination.
AB  - As multidetector computed tomography (CT) serves as an increasingly frequent
      diagnostic modality, radiation risks to patients became a greater concern,
      especially for children due to their inherently higher radiosensitivity to
      stochastic radiation damage. Current dose evaluation protocols include the
      computed tomography dose index (CTDI) or point detector measurements using
      anthropomorphic phantoms that do not sufficiently provide accurate information of
      the organ-averaged absorbed dose and corresponding effective dose to pediatric
      patients. In this study, organ and effective doses to pediatric patients under
      helical multislice computed tomography (MSCT) examinations were evaluated using
      an extensive series of anthropomorphic computational phantoms and Monte Carlo
      radiation transport simulations. Ten pediatric phantoms, five stylized (equation
      based) ORNL phantoms (newborn, 1-year, 5-year, 10-year, and 15-year) and five
      tomographic (voxel-based) UF phantoms (9-month male, 4-year female, 8-year
      female, 11-year male, and 14-year male) were implemented into MCNPX for
      simulation, where a source subroutine was written to explicitly simulate the
      helical motion of the CT x-ray source and the fan beam angle and collimator
      width. Ionization chamber measurements were performed and used to normalize the
      Monte Carlo simulation results. On average, for the same tube current setting, a
      tube potential of 100 kVp resulted in effective doses that were 105% higher than
      seen at 80 kVp, and 210% higher at 120 kVp regardless of phantom type. Overall,
      the ORNL phantom series was shown to yield values of effective dose that were
      reasonably consistent with those of the gender-specific UF phantom series for CT
      examinations of the head, pelvis, and torso. However, the ORNL phantoms
      consistently overestimated values of the effective dose as seen in the UF phantom
      for MSCT scans of the chest, and underestimated values of the effective dose for
      abdominal CT scans. These discrepancies increased with increasing kVp. Finally,
      absorbed doses to select radiation sensitive organs such as the gonads, red bone
      marrow, colon, and thyroid were evaluated and compared between phantom types.
      Specific anatomical problems identified in the stylized phantoms included
      excessive pelvic shielding of the ovaries in the female phantoms, enhanced red
      bone marrow dose to the arms and rib cage for chest exams, an unrealistic and
      constant torso thickness resulting in excessive x-ray attenuation in the regions
      of the abdominal organs, and incorrect positioning of the thyroid within the
      stylized phantom neck resulting in insufficient shielding by clavicles and
      scapulae for lateral beam angles. To ensure more accurate estimates of organ
      absorbed dose in multislice CT, it is recommended that voxel-based phantoms,
      potentially tailored to individual body morphometry, be utilized in any future
      prospective epidemiological studies of medically exposed children.

PMID- 17555268
TI  - Streptomyces turgidiscabies secretes a novel virulence protein, Nec1, which
      facilitates infection.
AB  - Emergence of new, economically important plant-pathogenic species in the mostly
      saprophytic genus Streptomyces involves acquisition of a large, mobile
      pathogenicity island (PAI). Biosynthetic genes for a phytotoxin, thaxtomin A, are
      contained on this PAI. The Nec1 protein has necrogenic activity on excised potato
      tuber tissue, and the encoding gene is highly conserved in plant-pathogenic
      Streptomyces spp. The G+C content of nec1 indicates lateral transfer from an
      unrelated taxon; however, the nucleic acid and protein databases have not yielded
      homologs. Data presented in this article demonstrate that the Nec1 protein is
      necrogenic when expressed in Escherichia coli and that an active 16-kDa form of
      Nec1 is secreted from the plant pathogen Streptomyces turgidiscabies. Deletion
      analysis of nec1 demonstrated that the 151-amino-acid C-terminal region of the
      Nec1 protein is sufficient to confer necrogenic activity. Analysis of nec1
      transcriptional start sites indicates that two mRNA species are produced and that
      the site of transcription initiation is influenced by glucose. S. turgidiscabies
      containing a nec1 deletion was greatly compromised in virulence on Arabidopsis
      thaliana, Nicotiana tabacum, and Raphanus sativus seedlings. The wild-type
      strain, S. turgidiscabies Car8, aggressively colonized and infected the root
      meristem of radish, whereas the deltanec1 mutant Car811 did not. Taken together,
      these data suggest that Nec1 is a secreted virulence protein with a conserved
      plant cell target that acts early in plant infection.

PMID- 17555269
TI  - Quantitative analysis of efficient endogenous gene silencing in Nicotiana
      benthamiana plants using tomato bushy stunt virus vectors that retain the capsid
      protein gene.
AB  - Tomato bushy stunt virus (TBSV) coat protein (CP) replacement vectors have been
      used previously to silence transgenes (e.g., the green fluorescent protein gene)
      but have not been effective for silencing endogenous plant genes. New TBSV
      vectors which retained the CP gene were developed by engineering an XhoI
      restriction site in three positions (3f, CEB, and CEA) of the pTBSV-100
      infectious clone. Magnesium chelatase (ChlH) and phytoene desaturase (PDS) were
      chosen as targets for endogenous gene silencing. Initial experiments using CP
      replacement vectors with a 230-bp sense or antisense ChlH insert gave a silencing
      phenotype prominent only in the first new leaves above those inoculated. No
      silencing phenotype was apparent beyond these leaves whereas, for PDS, no
      silencing phenotype was observed. When plants were inoculated with the XhoI
      insert vectors containing ChlH and PDS sequences, plants showed a silencing
      phenotype extensively throughout the challenged plant, indicating an improved
      ability for virus movement and silencing in Nicotiana benthamiana host plants.
      Silencing efficiencies were quantified using realtime reverse-transcription
      polymerase chain reaction, indicating specific silencing effects of each
      individual silencing vector. Only one recombinant vector (pPD-3f5), where the
      XhoI insert was at the 3' end of the CP gene, failed to give effective silencing.
      Here, we show that our new CP-retaining TBSV vectors (CEA-CEB) form typical TBSV
      virions, retain silencing inserts of variable lengths (110 to 260 nucleotides),
      and can systemically silence endogenous genes in N. benthamiana.

PMID- 17555270
TI  - Tryptophan-dependent production of indole-3-acetic acid (IAA) affects level of
      plant growth promotion by Bacillus amyloliquefaciens FZB42.
AB  - Phytohormone-like acting compounds previously have been suggested to be involved
      in the phytostimulatory action exerted by the plant-beneficial rhizobacterium
      Bacillus amyloliquefaciens FZB42. Analyses by high-performance liquid
      chromatography and gas chromatography-mass spectrometry performed with culture
      filtrates of FZB42 demonstrated the presence of indole-3-acetic acid (IAA),
      corroborating it as one of the pivotal plant-growth-promoting substances produced
      by this bacterium. In the presence of 5 mM tryptophan, a fivefold increase in IAA
      secretion was registered. In addition, in the trp auxotrophic strains E101
      (deltatrpBA) and E102 (deltatrpED), and in two other strains bearing knockout
      mutations in genes probably involved in IAA metabolism, E103 (deltaysnE, putative
      IAA transacetylase) and E105 (deltayhcX, putative nitrilase), the concentration
      of IAA in the culture filtrates was diminished. Three of these mutant strains
      were less efficient in promoting plant growth, indicating that the Trp-dependent
      synthesis of auxins and plant growth promotion are functionally related in B.
      amyloliquefaciens.

PMID- 17555271
TI  - RAS2 regulates growth and pathogenesis in Fusarium graminearum.
AB  - Fusarium graminearum is a ubiquitous pathogen of cereal crops, including wheat,
      barley, and maize. Diseases caused by F. graminearum are of particular concern
      because harvested grains frequently are contaminated with harmful mycotoxins such
      as deoxynivalenol (DON). In this study, we explored the role of Ras GTPases in
      pathogenesis. The genome of F. graminearum contains two putative Ras GTPase
      encoding genes. The two genes (RAS1 and RAS2) showed different patterns of
      expression under different conditions of nutrient availability and in various
      mutant backgrounds. RAS2 was dispensable for survival but, when disrupted, caused
      a variety of morphological defects, including slower growth on solid media,
      delayed spore germination, and significant reductions in virulence on wheat heads
      and maize silks. Intracellular cAMP levels were not affected by deletion of RAS2
      and exogenous treatment of the ras2 mutant with cAMP did not affect phenotypic
      abnormalities, thus indicating that RAS2 plays a minor or no role in cAMP
      signaling. However, phosphorylation of the mitogen-activated protein (MAP) kinase
      Gpmk1 and expression of a secreted lipase (FGL1) required for infection were
      reduced significantly in the ras2 mutant. Based on these observations, we
      hypothesize that RAS2 regulates growth and virulence in F. graminearum by
      regulating the Gpmk1 MAP kinase pathway.

PMID- 17555273
TI  - Phosphorylation of the termini of Cauliflower mosaic virus precapsid protein is
      important for productive infection.
AB  - Cauliflower mosaic virus (CaMV) coat protein precursor (pre-CP) has 489 amino
      acids (p57) and is processed by the viral proteinase into three major forms: p44,
      p39, and p37. The N- and C-terminal extensions of pre-CP are released during
      maturation by the virus-encoded proteinase. We showed that these extensions are
      phosphorylated at several sites by host casein kinase II (CKII). We have
      identified the phosphorylated amino acids using an in vitro phosphorylation assay
      and tested the effect of mutation of these sites on viral infectivity. Mutation
      of serines S66, S68, and S72 to alanine in the N-terminal extension abolished
      phosphorylation of the protein in vitro. Also, mutation of all S and T residues
      in the C-terminus (450 to 489) made this region insensitive to CKII. Amino acid
      substitutions also were introduced into a full-length infectious clone of CaMV.
      Mutated forms of the virus with S66, S68, and S72 substituted with A or D showed
      a delay in symptom development and affected the infectivity of the virus.
      However, a mutant with an A substitution of all the S and T residues of the C
      terminal extension of CP was not infectious. These results suggest that
      phosphorylation of the N- and C-termini of CaMV pre-CP plays an important role in
      the initiation of viral infection.

PMID- 17555272
TI  - Complementation of Ustilago maydis MAPK mutants by a wheat leaf rust, Puccinia
      triticina homolog: potential for functional analyses of rust genes.
AB  - From a large expressed sequence tag (EST) database representing several
      developmental stages of Puccinia triticina, we discovered a mitogen-activated
      protein kinase (MAPK) with homology to kinases with known pathogenic functions in
      other fungi. This PtMAPK1 is similar to the Ustilago maydis MAPK, Ubc3/Kpp2, but
      has a longer N-terminal extension of 43 amino acids (aa) with identities to U.
      maydis Kpp6, a homolog of Ubc3/Kpp2 with a 170-aa N-terminal extension. Ubc3/Kpp2
      is involved in mating and subsequent pathogenic development, whereas Kpp6
      functions during invasive growth in corn tissue. PtMAPK1, expressed from a
      Ustilago sp.-specific promoter, was able to complement a ubc3/kpp2 deletion
      mutant and restore mating. It also substantially increased virulence on corn,
      measured as tumor formation, of a kpp6 deletion mutant. Moreover, this construct
      restored to near-full pathogenicity a ubc3/kpp2 kpp6 nonpathogenic double
      deletion mutant. Complementation of the ubc3/kpp2 mutant with the complete PtMAPK
      gene and verification of expression by reverse-transcription polymerase chain
      reaction indicated that the rust promoter is recognized in U. maydis.
      Phylogenetically, these basidiomycete plant pathogens are related, which was
      reflected in comparison of P. triticina ESTs to U. maydis gene sequences. The U.
      maydis heterologous expression system allows functional analysis of rust genes,
      currently frustrated by the lack of efficient transformation and selection
      procedures.

PMID- 17555274
TI  - Components of Arabidopsis defense- and ethylene-signaling pathways regulate
      susceptibility to Cauliflower mosaic virus by restricting long-distance movement.
AB  - We analyzed the susceptibility of Arabidopsis mutants with defects in salicylic
      acid (SA) and jasmonic acid (JA)/ethylene (ET) signaling to infection by
      Cauliflower mosaic virus (CaMV). Mutants cpr1-1 and cpr5-2, in which SA-dependent
      defense signaling is activated constitutively, were substantially more resistant
      than the wild type to systemic infection, implicating SA signaling in defense
      against CaMV. However, SA-deficient NahG, sid2-2, eds5-1, and pad4-1 did not show
      enhanced susceptibility. A cpr5 eds5 double mutant also was resistant, suggesting
      that resistance in cpr5 may function partially independently of SA. Treatment of
      cpr5 and cpr5 eds5, but not cpr1, with salicyl-hydroxamic acid, an inhibitor of
      alternative oxidase, partially restored susceptibility to wild-type levels.
      Mutants etr1-1, etr1-3, and ein2-1, and two mutants with lesions in ET/JA
      mediated defense, eds4 and eds8, also showed reduced virus susceptibility,
      demonstrating that ET-dependent responses also play a role in susceptibility. We
      used a green fluorescent protein (GFP)-expressing CaMV recombinant to monitor
      virus movement. In mutants with reduced susceptibility, cpr1-1, cpr5-2, and etr1
      1, CaMV-GFP formed local lesions similar to the wild type, but systemic spread
      was almost completely absent in cpr1 and cpr5 and was substantially reduced in
      etr1-1. Thus, mutations with enhanced systemic acquired resistance or compromised
      ET signaling show diminished long-distance virus movement.

PMID- 17555275
TI  - Downregulation of the NbNACa1 gene encoding a movement-protein-interacting
      protein reduces cell-to-cell movement of Brome mosaic virus in Nicotiana
      benthamiana.
AB  - The 3a movement protein (MP) plays a central role in the movement of the RNA
      plant virus, Brome mosaic virus (BMV). To identify host factor genes involved in
      viral movement, a cDNA library of Nicotiana benthamiana, a systemic host for BMV,
      was screened with far-Western blotting using a recombinant BMV MP as probe. One
      positive clone encoded a protein with sequence similarity to the alpha chain of
      nascent-polypeptide-associated complex from various organisms, which is proposed
      to contribute to the fidelity of translocation of newly synthesized proteins. The
      orthologous gene from N. benthamiana was designated NbNACa1. The binding of
      NbNACa1 to BMV MP was confirmed in vivo with an agroinfiltration
      immunoprecipitation assay. To investigate the involvement of NbNACa1 in BMV
      multiplication, NbNACa1-silenced (GSNAC) transgenic N. benthamiana plants were
      produced. Downregulation of NbNACa1 expression reduced virus accumulation in
      inoculated leaves but not in protoplasts. A microprojectile bombardment assay to
      monitor BMV-MP-assisted viral movement demonstrated reduced virus spread in GSNAC
      plants. The localization to the cell wall of BMV MP fused to green fluorescent
      protein was delayed in GSNAC plants. From these results, we propose that NbNACa1
      is involved in BMV cell-to-cell movement through the regulation of BMV MP
      localization to the plasmodesmata.

PMID- 17555276
TI  - Mutation of Lon protease differentially affects the expression of Pseudomonas
      syringae type III secretion system genes in rich and minimal media and reduces
      pathogenicity.
AB  - The bacterial Lon protease participates in a variety of biological processes. In
      Pseudomonas syringae, mutation of lon is known to activate hrpL and a few hrpL
      regulated genes in rich medium. The elevated expression of hrpL and hrpL
      regulated genes results from increased stability of HrpR, the transcriptional
      activator of hrpL, in the lon mutant. Here, we conducted a microarray analysis to
      identify genes that are differentially expressed in a lon- mutant of P. syringae
      pv. tomato DC3000 grown in the rich medium King's B (KB). Most genes induced in
      the lon- mutant belong to the HrpL regulon or are related to transcription,
      protein synthesis, and energy metabolism. A major group of genes reduced in the
      lon- mutant are related to cell wall biogenesis. The HrpL-regulated genes exhibit
      different induction patterns in the lon- mutant, suggesting that additional
      regulators other than HrpL are likely to be involved in regulation of these
      genes. Compared with the wild-type bacteria, lon- mutants of P. syringae pv.
      tomato DC3000 and P. syringae pv. phaseolicola NPS3121 strains exhibit elevated
      hrpL expression in KB medium, but reduced hrpL expression in minimal medium (MM).
      The reduced hrpL RNA is correlated with reduced hrpR and hrpS RNAs, suggesting
      that the Lon-mediated regulation of hrpL involves different mechanisms in KB and
      MM. The lon- mutation also reduced bacterial pathogenicity.

PMID- 17555277
TI  - Is catalase activity one of the factors associated with maize resistance to
      Aspergillus flavus?
AB  - Plant responses to biotic and abiotic stresses are usually accompanied by the
      release of reactive oxygen species including hydrogen peroxide. Hydrogen peroxide
      plays a direct role in defense and is involved in many signal transduction
      pathways that lead to the proliferation of other defenses. Because catalase helps
      to maintain reactive oxygen homeostasis during biotic and abiotic stress, its
      activity was measured in various cob tissues during maize ear development.
      Catalase activity was determined in immature and mature embryos, pericarp, and
      rachis tissues of maize lines that are resistant and susceptible to Aspergillus
      flavus infection. The effect of fungal inoculation on catalase activity was also
      measured. Over two years of field experimentation, a correlation was observed
      between resistance and the level of catalase-specific activity in immature
      embryos, which was significantly higher in resistant lines (P < 0.0001).
      Furthermore, catalase activity in the resistant lines was significantly higher in
      immature embryos from inoculated ears (P = 0.0199). No correlation was observed
      between resistance and catalase activity in other ear tissues. Levels of hydrogen
      peroxide, the catalase substrate, and salicylic acid in the embryo were also
      determined. The resistant lines showed lower levels of H2O2 (P < 0.0001) and
      higher levels of salicylic acid (P < 0.0001) as compared with the susceptible
      lines. Catalase 3 was sequenced from the aflatoxin-resistant (Mp313E) and
      susceptible (SC212m) inbreds. The predicted amino acid sequence indicated that
      there was a 20-aa deletion in the resistant inbred that might affect enzymatic
      activity. Unlike many plant-pathogen interactions, it appears that lowering H2O2
      levels helps to prevent A. flavus infection and subsequent aflatoxin
      accumulation.

PMID- 17555278
TI  - Insect elicitors and exposure to green leafy volatiles differentially upregulate
      major octadecanoids and transcripts of 12-oxo phytodienoic acid reductases in Zea
      mays.
AB  - The induction of jasmonic acid (JA) is one of the major signaling events in
      plants in response to insect herbivore damage and leads to the activation of
      direct and indirect defensive measures. Green leafy volatiles, which constitute a
      major portion of volatile organic compounds, often are released in response to
      insect herbivore attack and have been shown to significantly activate JA
      production in exposed corn (Zea mays) seedlings, thereby priming these plants
      specifically against subsequent herbivore attack. To explore the factors
      determining the specificity of the octadecanoid signaling pathway in corn, we
      analyzed qualitative and quantitative changes in major octadecanoids. The time
      course and the amount of induced JA and 12-oxophytodienoic acid levels in corn
      seedlings were strikingly different after wounding, application of caterpillar
      regurgitant, or treatment with cis-3-hexenyl acetate (Z-3-6:AC). Exposure to Z-3
      6:AC induced accumulation of transcripts encoded by three putative 12
      oxophytodienoate10,11-reductase genes (ZmOPR1/2, ZmOPR5, and ZmOPR8). Although
      changes in ZmOPR5 RNAs were detected only after exposure to Z-3-6:AC, ZmOPR1/2
      RNAs and ZmOPR8 RNAs also were abundant after treatment with crude regurgitant
      elicitor or mechanical damage. The physiological implications of these findings
      in the context of plant-insect interactions are discussed.

PMID- 17555279
TI  - RNAi-mediated resistance to Bean golden mosaic virus in genetically engineered
      common bean (Phaseolus vulgaris).
AB  - Bean golden mosaic virus (BGMV) is transmitted by the whitefly Bemisia tabaci in
      a persistent, circulative manner, causing the golden mosaic of common bean
      (Phaseolus vulgaris L.). The characteristic symptoms are yellow-green mosaic of
      leaves, stunted growth, or distorted pods. The disease is the largest constraint
      to bean production in Latin America and causes severe yield losses (40 to 100%).
      Here, we explored the concept of using an RNA interference construct to silence
      the sequence region of the AC1 viral gene and generate highly resistant
      transgenic common bean plants. Eighteen transgenic common bean lines were
      obtained with an intron-hairpin construction to induce post-transcriptional gene
      silencing against the AC1 gene. One line (named 5.1) presented high resistance
      (approximately 93% of the plants were free of symptoms) upon inoculation at high
      pressure (more than 300 viruliferous whiteflies per plant during the whole plant
      life cycle) and at a very early stage of plant development. Transgene-specific
      small interfering RNAs were detected in both inoculated and non-inoculated
      transgenic plants. A semiquantitative polymerase chain reaction analysis revealed
      the presence of viral DNA in transgenic plants exposed to viruliferous whiteflies
      for a period of 6 days. However, when insects were removed, no virus DNA could be
      detected after an additional period of 6 days.

PMID- 17555280
TI  - Extracellular proteins of Clostridium chauvoei are protective in a mouse model.
AB  - The anaerobic bacillus Clostridium chauvoei is the causative agent of blackleg, a
      lethal disease that has an important impact on the sheep and cattle industry
      worldwide. Immunity to C. chauvoei is considered to be mainly anticellular, and
      for this reason there is scarce information about the immunogenicity of
      extracellular proteins. In this work variations in protein profiles, immune
      response by ELISA and protective capacity of culture supernatants of three C.
      chauvoei strains, collected at different growth phases, are reported. Sera raised
      against extracellular antigens also recognised cellular antigens of the same
      molecular masses. Partially purified cell-free supernatants and those
      concentrated 10 times by ultrafiltration (C-CFS), obtained at the early
      stationary phase of growth, induced a strong immunoprotective response, even at
      low doses, that was more marked for C. chauvoei strain ATCC 10092 (p < or =
      0.05). With C-CFS formulations, a clear relationship was observed between IgG
      titres, protective capacity and concentration of the antigen doses, indicating a
      specific immune response.

PMID- 17555281
TI  - Isolation and development of haematopoietic progenitor cells from peripheral
      blood of adult and newborn pigs.
AB  - Pluripotent stem cells (PSCs), already described in human beings, are fibroblast
      like cells that exhibit a CD34 marker specific for haematopoietic stem cells. In
      this work we have demonstrated the presence of PSCs in the peripheral blood of
      pigs, a species frequently used in transplantation studies as an animal model for
      human diseases. Differentiation into haematopoietic colonies (granulomacrophagic
      colonies, erythroid colonies and mixed colonies) has been carried out with the
      peripheral blood of adult and newborn pigs, using solely human commercial media.
      Peripheral blood mononuclear cells (PBMNCs) were cultured in semisolid
      methylcellulose based media enriched with recombinant human cytokines, achieving
      granulomacrophagic-colony forming unit (GM-CFU) and mixed-colony forming unit
      (Mix-CFU) growth with erythroblastic lineage proliferation in the presence of
      erythropoietin (Epo). In all the samples CFU growth was associated with the
      presence of recombinant human cytokine. No evidence of proliferation in control
      plates without cytokines was found. From liquid medium culture, a population of
      macrophages and CD34+ fibroblast like cells were retrieved 21 days after sowing.
      These findings allow us to think about the direct application of this simple and
      standardised method in several work fields such as the study of pharmacological
      effects of many drugs over the haematopoietic line and in the study of new
      strategies in cellular therapy for some human diseases.

PMID- 17555282
TI  - Effects of fasting and refeeding on the antioxidant system in cockerels and
      pullets.
AB  - The effect of fasting and refeeding on total antioxidant status (TAS),
      glutathione peroxidase (GSH-Px) activity and concentration of some non-enzymatic
      antioxidant compounds was studied in cockerels and pullets. Blood was collected
      before and after 48-h fasting and 24 h after refeeding. In cockerels, fasting
      resulted in a significant decrease of TAS and uric acid concentration. After
      refeeding, the concentration of TAS remained significantly lower as compared to
      the control level. At the same time, blood plasma level of total lipids increased
      in comparison to the control and post-fasting values. In pullets, fasting
      resulted in a significant decrease of whole blood haemolysate GSH-Px activity and
      blood plasma concentrations of albumin and uric acid. Simultaneously, a
      significant increase in total lipids and cholesterol was obtained. In pullets,
      refeeding resulted in a further decrease of TAS to undetectable values, a
      significant decrease of blood plasma cholesterol, and a significant increase of
      GSH-Px in the whole blood haemolysate and in blood plasma uric acid content. The
      results indicate that fasting has a negative impact on the antioxidant defence
      system of the blood, which leads to a reduced resistance to oxidative stress in
      both cockerels and pullets. However, pullets seem to be more susceptible to
      fasting-provoked oxidative stress than cockerels.

PMID- 17555283
TI  - Effects of tiletamine-zolazepam anaesthesia on plasma antioxidative status and
      some haematological parameters in sheep.
AB  - It is not clear whether the anaesthetic agents tiletamine and zolazepam have
      antioxidant or pro-oxidant effects. Therefore, this study was carried out to
      investigate the effects of tiletamine-zolazepam anaesthesia on
      oxidant/antioxidant status in blood plasma and on haematological parameters in 10
      healthy Awassi ewes. The tiletamine-zolazepam combination was administrated in a
      dose of 7.5 mg/kg intramuscularly. The animals were spontaneously breathing air
      during the procedure. Blood samples were collected by jugular venipuncture before
      induction and at 30, 60, 120 min, 24 h and 3 days after anaesthesia.
      Malondialdehyde concentration, an index of lipid peroxidation, was higher at 30,
      60, 120 min and 24 h (P < 0.05) than the baseline value in the plasma. The level
      of glutathione decreased (P < 0.05) at 30, 60 and 120 min, then returned to the
      baseline level. Beta-carotene concentration was lower (P < 0.05) than the
      baseline value during anaesthesia with the exception of its level at 120 min.
      Glutathione peroxidase and catalase activities decreased (P < 0.05) at the onset
      of anaesthesia, then returned to baseline values. There was no significant change
      in vitamin A level. Red blood cell count, haematocrit and haemoglobin
      concentration significantly decreased (P < 0.05) only at 30 min and thereafter
      they gradually returned to the baseline values. Based on the results tiletamine
      zolazepam anaesthesia seems to accelerate lipid peroxidation and to impair the
      enzymatic antioxidant defence in the blood plasma.

PMID- 17555284
TI  - Mechanical devices to help in PennHIP examination.
AB  - A modified PennHIP procedure (MPP), using specific mechanical holding devices,
      was used on 70 dogs and compared to the standard PennHIP method (SPM) used on 39
      dogs, in terms of technical effectiveness and the mean number of essential
      individuals within the X-ray room (EIXRR). The data using the Chi-squared test
      were consistent with the null hypothesis that the technical effectiveness was
      equal in the groups under investigation (P > 0.05). On the contrary, using the
      two-sample unpaired t-test the null hypothesis, that the mean EIXRR was equal,
      was rejected (P < 0.001). The estimated EIXRR was 3.4 +/- 0.7 and 5.7 +/- 1.2
      (mean +/- SD) for MPP and SPM, respectively. In conclusion, the MPP needs fewer
      EIXXR than the SPM and complies with the new recommendations in X-ray protection,
      which introduce the ALARA (as-low-as-reasonably-achievable) idea.

PMID- 17555285
TI  - Detection of equine X chromosome mosaicism in a mare using an equine X whole
      chromosome painting probe (WCPP)--a case report.
AB  - An infertile mare with hypoplastic ovaries was subjected to cytogenetic analysis.
      Fluorescence in situ hybridisation (FISH) using the equine X whole chromosome
      painting probe (WCPP) was carried out on a chromosome preparation obtained from
      blood lymphocyte culture. The number of analysed spreads was high (235) and in
      the X chromosome aneuploidy in mosaic form was diagnosed. The karyotype formula
      was 63,X / 64,XX / 65,XXX. The ratio of the three lines was 15%, 82% and 3%,
      respectively. The application of the FISH technique with WCPP is discussed.

PMID- 17555286
TI  - Pacheco's disease in a Hungarian zoo bird population: a case report.
AB  - An epizootic of Pacheco's disease is reported from a zoo bird population. The
      infection was introduced by wild-captured Patagonian conures (Cyanoliseus
      patagonus) despite 61 days of quarantine. The disease affected several parrot
      species and, interestingly, three out of seven bearded barbets (Lybius dubius).
      The mortality rate was 30.93%. Autopsy revealed abdominal hyperaemia with liver
      haemorrhages and, in less rapid cases, yellowish discoloration and fragility of
      the liver. Death was caused by the collapse of circulation. Histopathology
      demonstrated liver cell necrosis, disintegration of the lobular structure, and a
      few intranuclear inclusion bodies. Icosahedral virions were detected by electron
      microscopy. The virus was isolated in the allantoic cavity of embryonated chicken
      eggs as well as in chicken embryo fibroblast cell culture. A 281-bp-long fragment
      of psittacid herpesvirus DNA was detected by PCR in cell culture material and
      liver samples of the affected birds. To our knowledge this is the first report of
      Pacheco's disease in bearded barbets as well as the first occurrence of Pacheco's
      disease in Hungary.

PMID- 17555287
TI  - Prevalence of selected enteropathogenic bacteria in Hungarian finishing pigs.
AB  - The aim of this study was to obtain prevalence estimates about the most important
      enteropathogenic bacteria: Lawsonia intracellularis, Brachyspira hyodysenteriae,
      Brachyspira pilosicoli, Salmonella enterica and Clostridium perfringens A and C
      in Hungarian farrow-to-finish pig herds. A total of 31 herds were selected, from
      where six pooled faecal samples, each containing three individual rectal faecal
      samples were collected from fattening pigs of 5-6 months of age. All 186 samples
      were examined by polymerase chain reaction (PCR) for the presence of the
      pathogens mentioned above. Lawsonia intracellularis was found in 29 herds
      (93.55%) and in 108 samples (58.06%); B. hyodysenteriae in 14 herds (45.16%) and
      in 23 samples (12.37%); B. pilosicoli in 19 herds (61.29%) and in 53 samples
      (28.49%); S. enterica in 17 herds (54.83%) and in 40 samples (21.50%). We
      detected the presence of C. perfringens A in 19 herds (61.29%) and in 46 samples
      (24.73%), while C. perfringens C was found in 8 herds (25.81%) and in 11 samples
      (5.91%). All examined herds were infected with one or more of these agents. Herds
      with diarrhoea in the mid- to late finishing phase had almost 10 times higher
      prevalence of B. hyodysenteriae than herds without such a history.

PMID- 17555288
TI  - Veterinary aspects and perspectives of nutrigenomics: a critical review.
AB  - Nutrigenomics examines nutrient-gene interactions on a genome-wide scale.
      Increased dietary fat or higher non-esterified fatty acids (NEFA) from starvation
      induced mobilisation may enhance hepatic oxidation and decrease esterification of
      fatty acids by reducing the expression of the fatty acid synthase gene. The key
      factors are the peroxisome proliferator-activated receptors (PPARs). Dietary
      carbohydrates--both independently and through insulin effect--influence the
      transcription of the fatty acid synthase gene. Oleic acid or n-3 fatty acids
      downregulate the expression of leptin, fatty acid synthase and lipoprotein lipase
      in retroperitoneal adipose tissue. Protein-rich diets entail a shortage of mRNA
      necessary for expression of the fatty acid synthase gene in the adipocytes.
      Conjugated linoleic acids (CLAs) are activators of PPAR and also induce apoptosis
      in adipocytes. Altered rumen microflora produces CLAs that are efficient
      inhibitors of milk fat synthesis in the mammary gland ('biohydrogenation
      theory'). Oral zinc or cadmium application enhances transcription rate in the
      metallothionein gene. Supplemental CLA in pig diets was found to decrease feed
      intake and body fat by activating PPARgamma-responsive genes in the adipose
      tissue. To prevent obesity and type II diabetes, the direct modulation of gene
      expression by nutrients is also possible. Nutrigenomics may help in the early
      diagnosis of genetically determined metabolic disorders and in designing
      individualised diets for companion animals.

PMID- 17555289
TI  - Pathomorphological study on gastroduodenal ulceration in horses: localisation of
      lesions.
AB  - Gastroduodenal ulceration is a prevalent disease in foals and adult horses.
      Decreased performance as well as fatal complications relate to this syndrome. The
      objective of our study was to determine the prevalence of gastric ulceration in a
      mixed population of horses by postmortem examination and to evaluate a possible
      association between equine gastric ulcer syndrome (EGUS) and sex or age of the
      examined horses, to evaluate the localisation of lesions in the proximal part of
      the gastrointestinal tract and to determine the occurrence of gastric parasites.
      Postmortem examinations were performed on 71 horses over a period of 24 months.
      Gastric ulcers were found in 52 horses (73.2%). There was no significant
      association between age or sex and occurrence of gastric ulcers. In all horses
      the squamous mucosa lesions were localised near the margo plicatus (100% of the
      cases), whereas in 23 horses the lesions were near the margo plicatus and lesser
      curvature and in 7 horses at the greater curvature. In 18 horses the mucosa was
      affected in the whole extent of the margo plicatus and in 1 horse diffuse lesions
      of the squamous mucosa were noted. Lesions of the glandular mucosa were localised
      in 11 horses at the fundic area, in 1 horse they occurred in the pylorus, and in
      10 horses diffuse lesions of the glandular mucosa were recorded. A low prevalence
      of Gasterophilus intestinalis infection was detected (1 horse, 1.4%). We have
      confirmed that gastric ulcers are a common problem in horses and duodenal or
      oesophageal ulceration is rare (not a single case of the latter was found in this
      study). Lesions in the glandular mucosa of the stomach are more frequent in
      suckling foals than in older animals. Lesions of the glandular mucosa are also
      common in adult horses, and a complete gastroscopic examination including
      examination of the pylorus is advisable to evaluate this syndrome.

PMID- 17555290
TI  - Luteinising hormone attenuates the vascular response to norepinephrine.
AB  - The present study examines the direct effect of luteinising hormone (LH) on the
      reactivity of the porcine uterine artery to norepinephrine (NE). Three-mm-long
      arterial segments collected during the luteal phase of the oestrous cycle were
      mounted in an organ bath for isometric tension recording. After 30 min of
      equilibration in optimal passive tone, one part of the vessels was treated with
      10 ng/ml of LH in PBS (experimental), while a second part of the arterial
      segments was treated with 10 ng/ml of bovine serum albumin (BSA) in PBS
      (control). After 30 min of equilibration, NE was given to each organ bath in a
      cumulative concentration manner, ranging between 1 x 10(-8) mol/l to 3 x 10(-4)
      mol/l. NE caused a dose-dependent contraction of all experimental and control
      arteries. The addition of LH caused a rightward shift of the dose-response curve
      to NE. The corresponding EC50 values were 2.17 (+/- 0.39) micromol/l in PBS
      pretreated vessels and 3.35 (+/- 0.41) micromol/l in LH-pretreated vessels (P <
      0.05). The results of the present study demonstrate that LH attenuates the
      vascular response to NE in third-order branches of the uterine artery. Therefore,
      it can be suggested that besides the known effect of LH-hCG on the formation of
      vasoactive eicosanoids, an additional mechanism is involved in the direct action
      of LH on blood flow in the uterine arteries in pigs.

PMID- 17555291
TI  - Origin and characterisation of preovulatory follicles of hyperstimulated oestrous
      cycles in goats.
AB  - The origin and evolution of preovulatory follicles (POF) in 9 hyperstimulated
      (polyovulatory) Serrana goats were characterised. After oestrus synchronisation
      and detection, transrectal ovarian ultrasonography was performed daily during two
      complete oestrous cycles. Blood samples were taken every 4 h during 24 h after
      oestrus detection for preovulatory LH peak and twice a week for plasma
      progesterone determinations. The interovulatory interval of 14 oestrous cycles
      with double ovulations was 21.1 +/- 0.3 days. The onset of ovulatory follicular
      wave occurred 4 days (-3.9 +/- 0.3 days, n = 14) prior to the ovulation day (day
      0) with a POF size of 6.9 +/- 0.2 mm (n = 28). In goats with ovulations in both
      ovaries (78.6%), the emergence of the first POF occurred earlier (-4.1 +/- 0.3
      days) than the second POF (-3.3 +/- 0.2 days, n = 11, P < 0.05). No differences
      in the total number of follicles > or = 2 mm were found between the day of POF
      emergence (4.3 +/- 0.4) and the day before ovulation (3.5 +/- 0.3, P > 0.05).
      These results showed the existence of a delay between the emergence of first and
      second POF and suggest a weak dominance effect in goats with double ovulations.

PMID- 17555292
TI  - Simultaneous detection of three porcine viruses by multiplex PCR.
AB  - Specific oligonucleotide primers were selected and combined in a multiplex
      arrangement, in order to detect simultaneously three economically important
      porcine viruses by polymerase chain reaction (PCR). The pathogen panel was
      comprised of viruses that cause reproductive failure in infected herds:
      Aujeszky's disease virus (ADV), porcine parvovirus (PPV) and porcine respiratory
      and reproductive syndrome virus (PRRSV). In order to reduce the time required for
      the detection of the pathogens, the assay was optimised to a RapidCycler PCR
      instrument. The multiplex PCR assay was shown to be specific, sensitive and
      rapid, because the results were read in less than 60 min after sample
      preparation. Due to its speed, efficiency and sensitivity, the described rapid
      multiplex PCR assay serves as a useful novel tool in the veterinary diagnostic
      laboratories for the quick and complex detection of these important porcine
      pathogens.

PMID- 17555293
TI  - Analysis of self-assembled monolayers on gold surfaces using direct analysis in
      real time mass spectrometry.
AB  - Mass spectrometry was performed on self-assembled monolayers (SAMs) of
      dodecanethiol on gold using the new direct analysis in real time (DART)
      ionization technique. Observed peaks for the SAMs included monomers, dimers, and
      trimers of the SAM molecules, with the dimer and trimer relative peak heights
      enhanced as compared to the spectra for neat dodecanethiol. The possibility that
      the observed peaks were due to residual (noncovalently bonded) material on the
      surface was tested by attempting to observe residual dodecanol. No peaks
      corresponding to dodecanol were observed. These results indicate that DART is an
      excellent ionization method for the direct and unambiguous mass analysis of
      chemical species in self-assembled monolayers.

PMID- 17555294
TI  - Absolute quantitation of beta-lactoglobulin by protein liquid chromatography-mass
      spectrometry and its application to different milk products.
AB  - The absolute quantitation of proteins in biological matrixes is of great interest
      in many fields and can be accomplished by different methodologies. Here, a method
      for the absolute quantitation of the whey protein beta-lactoglobulin using
      protein liquid chromatography coupled to mass spectrometry is reported. The
      developed approach was characterized in detail and applied to the determination
      of beta-lactoglobulin contents in various milk products. A special focus was
      placed on the recovery rates of the isolation procedure and on robust
      quantitation by LC-MS. For these purposes protein internal standards were
      employed. The observed recovery rates of beta-lactoglobulin from various samples
      ranged from 100% for whole milk to just over 50% for a strongly processed yogurt
      based baby food product. The influence of processing was investigated in greater
      detail, showing that an increasing intensity of the applied heat treatment
      resulted in an increasing loss of beta-lactoglobulin. LC-MS quantitation at the
      protein level proved to be highly suitable, avoiding a potentially problematic
      digestion step. The use of an appropriate internal standard to compensate for
      sample losses during sample workup was shown to be essential for obtaining
      accurate results.

PMID- 17555295
TI  - Sol-gel-derived composite antimony-doped, tin oxide-coated clay-silicate
      semitransparent and conductive electrodes.
AB  - A new form of conductive and transparent porous composite electrode is
      introduced. The electrode material is composed of antimony-doped, tin oxide (ATO)
      coated mica platelets imbedded in sol-gel-derived silicate or methyl silicate
      network. The platelet clays self-align in a layered structure within the silicate
      film, an anisotropic construction that minimizes the ATO loading required to
      achieve electric percolation. Transparency and resistance as a function of clay
      loading is reported with typical values of 100 k Omega/square and 1.5 OD for a 20
      microm-thick film. The transparency is lower as compared to sputtered ATO
      glasses, but this is, as far as we know, the best method for the low-temperature
      preparation of transparent, porous, and electrically conductive (as opposed to
      the amply reported ionically conductive) electrode materials. Permselectivity
      induced by the silicate and clay ingredients is demonstrated by permeation of
      positively charged methyl viologen compared to negatively charged ferricyanide.
      Prussian blue-modified ATO-coated platelets dispersed in sol-gel-derived silicate
      were used to demonstrate feasibility of a transparent and electrically conductive
      porous electrochromic material.

PMID- 17555296
TI  - Nanostructured biosensor for measuring neuropathy target esterase activity.
AB  - Neuropathy target esterase (NTE) is a membrane protein found in human neurons and
      other cells, including lymphocytes. Binding of certain organophosphorus (OP)
      compounds to NTE is believed to cause OP-induced delayed neuropathy (OPIDN), a
      type of paralysis for which there is no effective treatment. Mutations in NTE
      have also been linked with serious neurological diseases, such as motor neuron
      disease. This paper describes development of the first nanostructured biosensor
      interface containing a catalytically active fragment of NTE known as NEST. The
      biosensor was fabricated using the layer-by-layer assembly approach, by
      immobilizing a layer of NEST on top of multilayers consisting of a
      polyelectrolyte (poly-L-lysine) and an enzyme (tyrosinase). The biosensor has a
      response time on the order of seconds and gives a concentration-dependent
      decrease in sensor output in response to a known NEST (and NTE) inhibitor.
      Potential applications of the biosensor include screening OP compounds for NTE
      inhibition and investigating the enzymology of wild-type and mutant forms of NTE.
      Although the development of a NEST biosensor was the primary purpose of this
      study, we found that the approach developed for NEST could also be extended to
      measure the activity of other esterases involved in neural processes, such as
      acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). On the basis of
      measured sensitivities, phenyl valerate was the preferred substrate for NEST and
      BChE, whereas phenyl acetate was better for AChE.

PMID- 17555297
TI  - Experimental and analytical variation in human urine in 1H NMR spectroscopy-based
      metabolic phenotyping studies.
AB  - 1H NMR spectroscopy potentially provides a robust approach for high-throughput
      metabolic screening of biofluids such as urine and plasma, but sample handling
      and preparation need careful optimization to ensure that spectra accurately
      report biological status or disease state. We have investigated the effects of
      storage temperature and time on the 1H NMR spectral profiles of human urine from
      two participants, collected three times a day on four different days. These were
      analyzed using modern chemometric methods. Analytical and preparation variation
      (tested between -40 degrees C and room temperature) and time of storage (to 24 h)
      were found to be much less influential than biological variation in sample
      classification. Statistical total correlation spectroscopy and discriminant
      function methods were used to identify the specific metabolites that were
      hypervariable due to preparation and biology. Significant intraindividual
      variation in metabolite profiles were observed even for urine collected on the
      same day and after at least 6 h fasting. The effect of long-term storage at
      different temperatures was also investigated, showing urine is stable if frozen
      for at least 3 months and that storage at room temperature for long periods (1-3
      months) results in a metabolic profile explained by bacterial activity.
      Presampling (e.g., previous day) intake of food and medicine can also strongly
      influence the urinary metabolic profiles indicating that collective detailed
      participant historical meta data are important for interpretation of metabolic
      phenotypes and for avoiding false biomarker discovery.

PMID- 17555298
TI  - Electrochemical behavior of L-cysteine and its detection at ordered mesoporous
      carbon-modified glassy carbon electrode.
AB  - In this paper, the electrochemical behavior of L-cysteine (CySH) was investigated
      thoroughly at an ordered mesoporous carbon-modified glassy carbon (OMC/GC)
      electrode. The voltammetric studies showed there were three anodic peaks for the
      electrooxidation of CySH in the pH range of 2.00-5.00; however, one peak
      disappeared above pH 5.00. This behavior has never been reported before. Through
      the studies of the effect of pH on the distribution fractions (delta) of the four
      chemical species of CySH, we conclude only CySH2+ (H3A+) and CyS- (HA-) are the
      electroactive substances and should be responsible for the electrooxidation of
      CySH. And for the first time, we successfully established the exact and systemic
      mechanisms based on the electroactive species to explain CySH oxidation at
      different pH values. On the other hand, a sensitive CySH sensor was developed
      based on an OMC/GC electrode, which shows a large determination range (18-2500
      micromol L(-1)), a high sensitivity (23.6 microA mmol L(-1)), and a remarkably
      low detection limit (2.0 nmol L(-1), which is the lowest value ever reported for
      direct CySH determination on the electrodes) at pH 2.00. At pH 7.00, the modified
      electrode can be still used to readily detect CySH in the range of the
      physiological levels. These make OMC/GC electrode a promising candidate for
      efficient electrochemical sensors for the detection of CySH.

PMID- 17555299
TI  - Carbon-13 labeling for quantitative analysis of molecular movement in
      heterogeneous organic materials using secondary ion mass spectrometry.
AB  - Secondary ion mass spectrometry (SIMS) is used to probe the movement of
      macromolecules in heterogeneous organic systems. Using 13C tracer labeling and
      two model systems, polystyrene/poly(2-vinylpyridine) (PS/P2VP) and
      polystyrene/poly(4-bromostyrene) (PS/P4BrS), the diffusion of 13C-labeled PS has
      been investigated near the respective heterogeneous interfaces using a CAMECA-IMS
      6F magnetic sector mass spectrometer. 13C labeling has been shown to greatly
      minimize matrix effects (i.e., changes in secondary ion yields due to changing
      chemical environment) in heterogeneous systems. P2VP is a nitrogen-rich polymer
      (C7H7N monomer composition), making it an excellent model polymer for exploration
      of this technique for potential future use in biological applications, and
      probing the PS/P4BrS interface demonstrates the versatility of this technique for
      analysis of various heteroatom-containing materials. Results confirm that the 13C
      labeling method does indeed allow for quantitative analysis of molecular movement
      in heterogeneous organic systems containing matrix-enhancing heteroatoms such as
      nitrogen. Therefore, extension of this method to more complicated biological
      systems involving multiple heteroatoms (oxygen, nitrogen, etc.), layers, and
      heterogeneous interfaces, as well as two- and three-dimensional profiling and
      imaging using SIMS, can be envisaged.

PMID- 17555300
TI  - Simultaneous laser-induced fluorescence and scattering detection of individual
      particles separated by capillary electrophoresis.
AB  - This technical note describes a detector capable of simultaneously monitoring
      scattering and fluorescence signals of individual particles separated by
      capillary electrophoresis. Due to its nonselective nature, scattering alone is
      not sufficient to identify analyte particles. However, when the analyte particles
      are fluorescent, the detector described here is able to identify simultaneously
      occurring scattering and fluorescent signals, even when contaminating particles
      (i.e., nonfluorescent) are present. Both fluorescent polystyrene particles and 10
      nonyl acridine orange (NAO)-labeled mitochondria were used as models.
      Fluorescence versus scattering (FVS) plots made it possible to identify two types
      of particles and a contaminant in a mixture of polystyrene particles. We also
      analyzed NAO-labeled mitochondria before and after cryogenic storage; the
      mitochondria FVS plots changed with storage, which suggests that the detector
      reported here is suitable for monitoring subtle changes in mitochondrial
      morphology that would not be revealed by monitoring only fluorescence or
      scattering signals.

PMID- 17555302
TI  - Characteristic features in the collision of chemical waves depending on the
      aspect ratio of a rectangular field.
AB  - The photosensitive Belousov-Zhabotinsky (BZ) reaction was investigated on a
      double rectangular field composed of two rectangular routes, which was drawn
      using computer software and then projected using a liquid-crystal projector on a
      filter paper soaked with BZ solution. When two chemical waves were generated on
      the rectangular routes as the initial condition, the nature of the collision of
      the waves could be theoretically classified into four categories depending on the
      initial phase difference between the two waves and the aspect ratio of the
      rectangular routes. The experimental results were consistent with the features of
      the theoretical prediction. These results suggest that the feature of wave
      propagation characteristically develops depending on the geometry of the
      excitable fields.

PMID- 17555301
TI  - Allosteric mechanisms in cytochrome P450 3A4 studied by high-pressure
      spectroscopy: pivotal role of substrate-induced changes in the accessibility and
      degree of hydration of the heme pocket.
AB  - Allosteric mechanisms in human cytochrome P450 3A4 (CYP3A4) in oligomers in
      solution or monomeric enzyme incorporated into Nanodiscs (CYP3A4ND) were studied
      by high-pressure spectroscopy. The allosteric substrates 1-pyrenebutanol (1-PB)
      and testosterone were compared with bromocriptine (BCT), which shows no
      cooperativity. In both CYP3A4 in solution and CYP3A4ND, we observed a complete
      pressure-induced high-to-low spin shift at pressures of <3 kbar either in the
      substrate-free enzyme or in the presence of BCT. In addition, both substrate-free
      and BCT-bound enzyme revealed a pressure-dependent equilibrium between two states
      with different barotropic parameters designated R for relaxed and P for pressure
      promoted conformations. This pressure-induced conformational transition was also
      observed in the studies with 1-PB and testosterone. In CYP3A4 oligomers, the
      transition was accompanied by an important increase in homotropic cooperativity
      with both substrates. Surprisingly, at high concentrations of allosteric
      substrates, the amplitude of the spin shift in both CYP3A4 in solution and
      Nanodiscs was very low, demonstrating that hydrostatic pressure induces neither
      substrate dissociation nor an increase in the heme pocket hydration in the
      complexes of the pressure-promoted conformation of CYP3A4 with 1-PB or
      testosterone. These findings suggest that the mechanisms of interactions of
      CYP3A4 with 1-PB and testosterone involve an effector-induced transition that
      displaces a system of conformational equilibria in the enzyme toward the state(s)
      with decreased solvent accessibility of the active site so that the flux of water
      into the heme pocket is impeded and the high-spin state of the heme iron is
      stabilized.

PMID- 17555303
TI  - Exploring SCC-DFTB paths for mapping QM/MM reaction mechanisms.
AB  - A new first-order procedure for locating transition structures (TS) that employs
      hybrid quantum mechanical/molecular mechanical (QM/MM) potentials has been
      developed. This new technique (RPATh+RESD) combines the replica path method
      (RPATh) and standard reaction coordinate driving (RCD) techniques in an approach
      that both efficiently determines reaction barriers and successfully eliminates
      two key weaknesses of RCD calculations (i.e., hysteresis/discontinuities in the
      path and the sequential nature of the RCD procedure). In addition, we have
      extended CHARMM's QM/MM reaction pathway methods, the RPATh and nudged elastic
      band (NEB) methods, to incorporate SCC-DFTB wave functions. This newly added
      functionality has been applied to the chorismate mutase-catalyzed interconversion
      of chorismate to prephenate, which is a key step in the shikimate pathway of
      bacteria, fungi, and other higher plants. The RPATh+RESD barrier height
      (DeltaE=5.7 kcal/mol) is in good agreement with previous results from full-energy
      surface mapping studies (Zhang, X.; Zhang, X.; Bruice, T. C. Biochemistry 2005,
      44, 10443-10448). Full reaction paths were independently mapped with RPATh and
      NEB methods and showed good agreement with the final transition state from the
      RPATh+RESD "gold standard" and previous high-level QM/MM transition states
      (Woodcock, H. L.; Hodoscek, M.; Gilbert, T. B.; Gill, P. M. W.; Schaefer, H. F.;
      Brooks, B. R. J. Comput. Chem. 2007, 28, 1485-1502). The SCC-DFTB TS geometry
      most closely approximates the MP2/6-31+G(d) QM/MM result. However, the barrier
      height is underestimated and possibly points to an area for improvement in SCC
      DFTB parametrization. In addition, the steepest descents (SD) minimizer for the
      NEB method was modified to uncouple the in-path and off-path degrees of freedom
      during the minimization, which significantly improved performance. The
      convergence behavior of the RPATh and NEB was examined for SCC-DFTB wave
      functions, and it was determined that, in general, both methods converge at about
      the same rate, although the techniques used for convergence may be different. For
      instance, RPATh can effectively use the adopted basis Newton-Raphson (ABNR)
      minimizer, where NEB seems to require a combination of SD and ABNR.

PMID- 17555304
TI  - Computational study on spectral properties of the selected pigments from various
      photosystems: structure-transition energy relationship.
AB  - In this study, the most important kinds of pigments (chlorophylls,
      bacteriochlorophylls, phycobilins, and carotenoids) from various photosystems
      were explored. For the most stable conformations, electronic transitions were
      determined at the TDDFT/6-31+G(d) level with the B3PW91 functional and compared
      to measured spectra. The group of carotenoids was also investigated at the
      TDA/TDDFT level with the BLYP functional. The energies of Qy transitions are
      systematically blue-shifted by about 50-100 nm in the case of
      (bacterio)chlorophyll and pheophytin molecules. Nevertheless, the correct
      relative order of the Q lines among various chlorophyll types was obtained
      through comparison with experimental results. Much better agreement was obtained
      for the Soret band, for which the differences between calculated and measured
      transitions were at most 35 nm. In the case of phycobilins, the first transition
      line was estimated to be at lower frequencies (around 500 nm) with a very similar
      blue shift of about 100 nm from experimental values. The influence of anchoring
      cysteine side chain(s) was found to be marginal. A dominant effect of the linear
      polyene chain on the determined spectral lines was found in the case of
      carotenoids. Nevertheless, the impact of beta-cycles and epoxy and keto groups is
      clearly visible as well. The high intensity of the first allowed transition
      matches different characters of the HOMO and LUMO. In the case of fucoxanthin,
      the TDA method also predicts the Bu- state to lie below the 1Bu+ state. Because
      the shift of electron transitions is approximately proportional to the size of
      the pi-conjugated system, the shift of the calculated transitions compared to
      experimental values is practically constant for the same excitations of
      (bacterio)chlorophyll and phycobilin molecules. However, this is not true for
      carotenoids, for which both the transition energy and the shift of the transition
      vary with the number of conjugated double bonds.

PMID- 17555305
TI  - Application of the computationally efficient self-consistent-charge density
      functional tight-binding method to magnesium-containing molecules.
AB  - The geometric properties, ionization potentials, heats of formation, incremental
      binding energies, and protonation energies for up to 75 magnesium-containing
      compounds have been studied using the self-consistent-charge density-functional
      tight-binding method (SCC-DFTB), the complete-basis set (CBS-QB3) method,
      traditional B3LYP density-functional theory, and a number of modern semiempirical
      methods such as Austin Model 1 (AM1), modified neglect of diatomic overlap
      without and with inclusion of d functions (MNDO, MNDO/d), and the Parametric
      Method 3 (PM3) and its modification (PM5). The test set contains some widely
      varying chemical motifs including ionic or covalent, closed-shell or radical
      compounds, and many biologically relevant complexes. Geometric data are compared
      to experiment, if available, and otherwise to previous high-level ab initio
      calculations or the present B3LYP results. SCC-DFTB is found to predict bond
      lengths to high accuracy, with the root-mean-square (RMS) error being less than
      half that found for the other semiempirical methods. However, SCC-DFTB performs
      very poorly for absolute heats of formation, giving an RMS error of 29 kcal mol(
      1), but for this property B3LYP and the other semiempirical methods also yield
      poor but useful results with errors of 12-22 kcal mol(-1). Nevertheless, SCC-DFTB
      does provide useful results for biologically relevant chemical-process energies
      such as protonation energies (RMS error 10 kcal mol(-1), with the range 6-19 kcal
      mol(-1) found for the other semiempirical methods) and ligation energies (RMS
      error 9 kcal mol(-1), less than the errors of 12-23 kcal mol(-1) found for the
      other semiempirical methods). SCC-DFTB is shown to provide a computationally
      expedient means of calculating properties of magnesium compounds, providing
      results with at most double the inaccuracy of the high-quality but dramatically
      more-expensive B3LYP method.

PMID- 17555306
TI  - o-Naphthalenedicarboxaldehyde derivative of 7'-aminonaltrindole as a selective
      delta-opioid receptor affinity label.
AB  - Incorporation of a naphthalene-dialdehyde moiety into the delta antagonist, 6'
      aminonaltrindole afforded a potent, selective, irreversible delta-agonist 1.
      However, flow cytometry studies revealed no time-dependent specific fluorescence,
      suggesting that both Lys214 and Cys216 at the recognition site are not involved
      in covalent binding. Molecular simulation studies suggest that compound 1 may
      form a Schiff base with the epsilon-amino group of Lys214, which could explain
      its irreversibility and transformation into a delta-agonist through a
      conformational change of TM5.

PMID- 17555307
TI  - Synthesis, biochemical, and cellular evaluation of farnesyl monophosphate
      prodrugs as farnesyltransferase inhibitors.
AB  - Certain farnesyl diphosphate (FPP) analogs are potent inhibitors of the potential
      anticancer drug target protein farnesyltransferase (FTase), but these compounds
      are not suitable as drug candidates. Thus, phosphoramidate prodrug derivatives of
      the monophosphate precursors of FPP-based FTase inhibitors have been synthesized.
      The monophosphates themselves were significantly more potent inhibitors of FTase
      than the corresponding FPP analogs. The effects of the prodrug 5b (a derivative
      of 3-allylfarnesyl monophosphate) have been evaluated on prenylation of RhoB and
      on the cell cycle in a human malignant schwannoma cell line (STS-26T). In
      combination treatments, 1-3 microM 5b plus 1 microM lovastatin induced a
      significant inhibition of RhoB prenylation, and a combination of these drugs at 1
      microM each also resulted in significant cell cycle arrest in G1. Indeed,
      combinations as low as 50 nM lovastatin + 1 microM 5c or 250 nM lovastatin + 50
      nM 5c were highly cytostatic in STS-26T cell culture.

PMID- 17555308
TI  - Discovery of a new nucleoside template for human A3 adenosine receptor ligands: D
      4'-thioadenosine derivatives without 4'-hydroxymethyl group as highly potent and
      selective antagonists.
AB  - Truncated D-4'-thioadenosine derivatives lacking the 4'-hydroxymethylene moiety
      were synthesized starting from D-mannose, using cyclization to the 4-thiosugar
      and one-step conversion of the diol to the acetate as key steps. At the human A3
      adenosine receptor (AR), N6-substituted purine analogues bound potently and
      selectively and acted as antagonists in a cyclic AMP functional assay. An N6-(3
      chlorobenzyl)purine analogue 9b displayed a Ki value of 1.66 nM at the human A3
      AR. Thus, truncated D-4'-thioadenosine is an excellent template for the design of
      novel A3 AR antagonists to act at both human and murine species.

PMID- 17555309
TI  - Radial basis function network-based transform for a nonlinear support vector
      machine as optimized by a particle swarm optimization algorithm with application
      to QSAR studies.
AB  - The support vector machine (SVM) has been receiving increasing interest in an
      area of QSAR study for its ability in function approximation and remarkable
      generalization performance. However, selection of support vectors and intensive
      optimization of kernel width of a nonlinear SVM are inclined to get trapped into
      local optima, leading to an increased risk of underfitting or overfitting. To
      overcome these problems, a new nonlinear SVM algorithm is proposed using adaptive
      kernel transform based on a radial basis function network (RBFN) as optimized by
      particle swarm optimization (PSO). The new algorithm incorporates a nonlinear
      transform of the original variables to feature space via a RBFN with one input
      and one hidden layer. Such a transform intrinsically yields a kernel transform of
      the original variables. A synergetic optimization of all parameters including
      kernel centers and kernel widths as well as SVM model coefficients using PSO
      enables the determination of a flexible kernel transform according to the
      performance of the total model. The implementation of PSO demonstrates a
      relatively high efficiency in convergence to a desired optimum. Applications of
      the proposed algorithm to QSAR studies of binding affinity of HIV-1 reverse
      transcriptase inhibitors and activity of 1-phenylbenzimidazoles reveal that the
      new algorithm provides superior performance to the backpropagation neural network
      and a conventional nonlinear SVM, indicating that this algorithm holds great
      promise in nonlinear SVM learning.

PMID- 17555310
TI  - Automated pharmacophore query optimization with genetic algorithms - a case study
      using the MC4R system.
AB  - Due to the recent availability of high quality small molecule databases, such as
      ZINC and PubChem,1,2 virtual screening is playing an even more important role in
      identifying biologically relevant molecules in drug discovery campaigns. The
      success of pharmacophore-based virtual screening (PBVS) relies largely on the
      accuracy and specificity of the pharmacophore query employed. Deriving a
      pharmacophore query from a single structure inevitably introduces uncertainty,
      and the derived query is unlikely to be optimal against every collection of input
      compounds, especially when it is desired to discriminate among compounds with
      similar chemical structures. In this study, we present an optimization approach
      empowered by genetic algorithms (GA) to enhance the accuracy and specificity of a
      primary pharmacophore query. The example utilized is the human melanocortin type
      4 receptor (hMC4R), for which the pharmacophore query was built on the basis of
      the structure of a rigid cyclic peptide agonist.(3) The optimized query is shown
      to be capable of identifying 37 positive hMC4R agonists with no false positives
      from a training set containing 55 agonists and 51 nonagonists. This represents a
      significant improvement from the initial query which exhibited a 37/32 hit rate.
      The final, optimized query is challenged with a testing set comprising of 55
      hMC4R agonists and 50 nonagonists and achieves a hit rate of 33/8, that improved
      from 40/31. The impact of GA controlling parameters, including mutation rate,
      crossover rate, fitness function, population size, and convergence criterion, on
      performance of optimization are examined and discussed.

PMID- 17555311
TI  - Chemoinformatic analysis of NCI preclinical tumor data: evaluating compound
      efficacy from mouse xenograft data, NCI-60 screening data, and compound
      descriptors.
AB  - We provide a chemoinformatic examination of the NCI public human tumor xenograft
      data to explore relationships between small molecules, treatment modality,
      efficacy, and toxicity. Efficacy endpoints of tumor weight reduction (TW) and
      survival time increase (ST) compared to tumor bearing control mice were augmented
      by a toxicity measure, defined as the survival advantage of treated versus
      control animals (TX). These endpoints were used to define two independent
      therapeutic indices (TIs) as the ratio of efficacy (TW or ST) to toxicity (TX).
      Linear models predictive of xenograft endpoints were successfully constructed
      (0.67 < r(2) < or = 0.74)(observed_versus_predicted) using a model comprised of
      variables in treatment modality, chemoinformatic descriptors, and in vitro cell
      growth inhibition in the NCI 60-cell assay. Cross-validation analysis based on
      randomly chosen training subsets found these predictive correlations to be
      robust. Model-based sensitivity analysis found chemistry and growth inhibition to
      provide the best, and treatment modality the worst, indicators of xenograft
      endpoint. The poor predictive power derived from treatment alone appears to be of
      less importance to xenograft outcome for compounds having strongly similar
      chemical and biological features. ROC-based model validation found a 70% positive
      predictive value for distinguishing FDA approved oncology agents from available
      xenograft tested compounds. Additional chemoinformatic applications are provided
      that relate xenograft outcome to biological pathways and putative mechanism of
      compound action. These results find a strong relationship between xenograft
      efficacy and pathways comprised of genes having highly correlated mRNA
      expressions. Our analysis demonstrates that chemoinformatic studies utilizing a
      combination of xenograft data and in vitro preclinical testing offer an effective
      means to identify compound classes with superior efficacy and reduced toxicity.

PMID- 17555312
TI  - Hydrolytic cleavage of DNA by a ruthenium(II) polypyridyl complex.
AB  - The complex [Ru(bpy)2(BPG)]Cl2 (1) containing hydrogen-bond donor (N-H atoms) and
      acceptor (O atoms) groups mediates hydrolytic cleavage of plasmid pBR322 DNA in
      an enzyme-like manner. The kinetic aspects of DNA cleavage under pseudo- and true
      Michaelis-Menten conditions are detailed.

PMID- 17555313
TI  - Hydrogen and copper ion-induced molecular reorganizations in scorpionand-like
      ligands. A potentiometric, mechanistic, and solid-state study.
AB  - Two aza scorpionand-like macrocycles (L2 and L3) have been prepared. L2 consists
      of a tren amine with two of its arms cyclizized with a 2,6
      bis(bromomethyl)pyridine. In L3, the remaining pendant arm has been further
      functionalized with a fluorophoric naphthalene group. X-ray data on the compounds
      [H(L3)]ClO4.H2O (1) and [H3(L3)](H2PO4)3.H2O (2) as well as solution studies (pH
      metry, UV-vis, and fluorescence data) show the movement of the pendant arm as a
      result of the protonation degree of the macrocycles and of the formation of
      intramolecular hydrogen bonds. X-ray data on the complexes [Cu(L2)](ClO4)2]2.H2O
      (3) and [Cu(L3)](ClO4)2 (4) and solution studies on Cu2+ coordination show the
      implication of the nitrogen of the arm in the binding to the metal ion. Kinetic
      studies on the decomposition and formation of the Cu2+ complexes provide
      additional information about the pH-dependent molecular reorganizations.
      Moreover, the obtained information suggests that the kinetics of the tail on/off
      process is essentially independent of the lability of the metal center.

PMID- 17555314
TI  - Activity of rhodium-catalyzed hydroformylation: added insight and predictions
      from theory.
AB  - We have performed a density functional theory investigation of hydroformylation
      of ethylene for monosubstituted rhodium-carbonyl catalysts, HRh(CO)3L, where the
      modifying ligand, L, is a phosphite (L = P(OMe)3, P(OPh)3, or P(OCH2CF3)3), a
      phosphine (L = PMe3, PEt3, PiPr3, or PPh3), or a N-heterocyclic carbene (NHC)
      based on the tetrahydropyrimidine, imidazol, or tetrazol ring, respectively. The
      study follows the Heck and Breslow mechanism. Excellent correspondence between
      our calculations and existing experimental information is found, and the present
      results constitute the first example of a realistic quantum chemical description
      of the catalytic cycle of hydroformylation using ligand-modified rhodium carbonyl
      catalysts. This description explains the mechanistic and kinetic basis of the
      contemporary understanding of this class of reaction and offers unprecedented
      insight into the electronic and steric factors governing catalytic activity. The
      insight has been turned into structure-activity relationships and used as
      guidelines when also subjecting to calculation phosphite and NHC complexes that
      have yet to be reported experimentally. The latter calculations illustrate that
      it is possible to increase the electron-withdrawing capacity of both phosphite
      and NHC ligands compared to contemporary ligands through directed substitution.
      Rhodium complexes of such very electron-withdrawing ligands are predicted to be
      more active than contemporary catalysts for hydroformylation.

PMID- 17555315
TI  - Synthesis and characterization of monodisperse poly(organosiloxane) nanocapsules
      with or without magnetic cores.

PMID- 17555316
TI  - Exploring experimental sources of multiple protein conformations in structure
      based drug design.
AB  - Receptor flexibility must be incorporated into structure-based drug design in
      order to portray a more accurate representation of a protein in solution. Our
      approach is to generate pharmacophore models based on multiple conformations of a
      protein and is very similar to solvent mapping of hot spots. Previously, we had
      success using computer-generated conformations of apo human immunodeficiency
      virus-1 protease (HIV-1p). Here, we examine the use of an NMR ensemble versus a
      collection of crystal structures, and we compare back to our previous study based
      on computer-generated conformations. To our knowledge, this is the first direct
      comparison of an NMR ensemble and a collection of crystal structures to
      incorporate protein flexibility in structure-based drug design. To provide an
      accurate comparison between the experimental sources, we used bound structures
      for our multiple protein structure (MPS) pharmacophore models. The models from an
      NMR ensemble and a collection of crystal structures were both able to
      discriminate known HIV-1p inhibitors from decoy molecules and displayed superior
      performance over models created from single conformations of the protein.
      Although the active-site conformations were already predefined by bound ligands,
      the use of MPS allows us to overcome the cross-docking problem and generate a
      model that does not simply reproduce the chemical characteristics of a specific
      ligand class. We show that there is more structural variation between 28
      structures in an NMR ensemble than 90 crystal structures bound to a variety of
      ligands. MPS models from both sources performed well, but the model determined
      using the NMR ensemble appeared to be the most general yet accurate
      representation of the active site. This work encourages the use of NMR models in
      structure-based design.

PMID- 17555317
TI  - Synthesis and characterization of meso-triarylsubporphyrins.
AB  - The synthesis of several meso-triaryl-subporphyrins, based on utilizing
      tripyrrolylborane as a precursor in a reaction with arylaldehydes (where aryl =
      phenyl, 4- and 3-pyridyl, tolyl, 4-methoxyphenyl, and 4-(trifluoromethyl)phenyl)
      under reflux in propionic acid, is reported. All of the compounds have been
      successfully characterized by 1H-, 13C-, and 13C-1H 2D NMR, electronic
      absorption, magnetic circular dichroism (MCD), IR, and fluorescence spectroscopy,
      together with cyclic (CV) and differential pulse (DPV) voltammetry. The X-ray
      structure of tris{(trifluoromethyl)phenyl}subporphyrin was found to be slightly
      domed and similar to that of the recently reported hexaethylsubtriazaporphyrin
      (Inorg. Chem. 2006, 45, 6148). The electronic absorption spectra of all of the
      subporphyrins contain intense Soret bands in the 370-380 nm region and weaker Q
      bands in the 420-550 nm region, which are at shorter wavelengths than those
      observed (at ca. 400-420 nm and ca. 450-650 nm, respectively) for tetrapyrrole
      porphyrins. The intensity of the Q00 band decreases as the meso-aryl groups
      become more electron withdrawing. These characteristics can be rationalized by
      using Gouterman's four-orbital model as a conceptual framework. The MCD bands
      observed in the Q band region of the subporphyrins (subPs) spectra consistently
      show a -ve/+ve intensity pattern in ascending energy, while, in contrast, the
      sign sequence of the bands observed in the Soret band region change dramatically
      depending on the nature of the aryl groups: from +ve/-ve in the case of the
      electron withdrawing 4-pyridyl, 4-(trifluoromethyl)phenyl and 3-pyridyl groups to
      -ve only for phenyl and -ve/+ve for the electron donating 4-tolyl and 4
      methoxyphenyl groups. S1 fluorescence emission was observed in the 490-620 nm
      region. The quantum yields (phiF) in benzene (phiF = 0.10-0.12) are similar to
      that of metal-free tetraphenylporphyrin (H2TPP) (phiF = 0.11) but are somewhat
      lower in the case of ethanol (phiF = 0.06-0.07) due to the higher polarity. The
      redox potential differences observed between the first oxidation and reduction
      steps are in the 2.52-2.64 V range, which is larger than that of normal
      porphyrins (ca. 2.25 V). Molecular orbital (MO) calculations of these compounds
      help to provide an enhanced understanding of the spectroscopic and
      electrochemical properties. A byproduct of the synthesis was characterized using
      X-ray crystallography and a range of spectroscopic techniques. A subporphyrin mu
      oxo dimer was prepared and characterized.

PMID- 17555318
TI  - Two components in a molecule: highly efficient and thermally robust catalytic
      system for CO(2)/epoxide copolymerization.

PMID- 17555319
TI  - Development of a Nazarov cyclization/Wagner-Meerwein rearrangement sequence for
      the stereoselective synthesis of spirocycles.

PMID- 17555321
TI  - Monodispersive linear supermolecules stabilizing unusual fluid layered phases.
AB  - The first examples of monodisperse liquid crystalline pentamers, synthesized by
      covalently linking five mesogenic segments through four flexible spacers,
      exhibiting mono-/partially bilayered phases with unusual textures, as established
      by optical, calorimetric, and X-ray diffraction studies, are reported.
      Importantly, the two types of multifunctional pentamers, namely, unsymmetric and
      C2 symmetric are soluble in organic solvents and exhibit analogous
      electrochemical features.

PMID- 17555322
TI  - Isotope effects in photochemistry: application to chromatic orthogonality.
AB  - The main challenge in developing new wavelength-specific photolabile protecting
      groups is the rigorous control of the photolysis rate. This rate is controlled by
      two factors: the chromophore absorbance and the reaction quantum yield. Fine
      tuning the properties by changing substituents or structural features is
      difficult, because both factors are independently affected. By the use of the
      kinetic isotope effect, we could tune the quantum yield without altering the
      absorbance, and hence control the overall reaction rate. We exemplified this
      approach with chromatically orthogonally protected diesters.

PMID- 17555323
TI  - [(NHC)AuI]-catalyzed rearrangement of allylic acetates.
AB  - [(NHC)AuCl] complexes (NHC = N-heterocyclic carbene), in conjunction with a
      silver salt, were found to efficiently catalyze the rearrangement of allylic
      acetates under both conventional and microwave-assisted heating. The optimization
      of several reaction parameters (solvent, silver salt, and ligand) as well as a
      study of the reaction scope are reported. The steric hindrance of the ligand
      bound to gold was found crucial for the outcome of the reaction as only extremely
      bulky ligands permitted the isomerization.

PMID- 17555324
TI  - Asymmetric hydroformylation of vinyl acetate: application in the synthesis of
      optically active isoxazolines and imidazoles.
AB  - (R)- and (S)-2-(Acetyloxy)-propanal were prepared [93.8% ee, 102 b/l for (R),
      96.9% ee, 149 b/l for (S)] via asymmetric hydroformylation of vinyl acetate on a
      150-180 g scale and were used as the starting materials in the synthesis of
      chiral isoxazoline and imidazole derivatives which proceeded without racemization
      of the chiral center.

PMID- 17555325
TI  - Benzothiazines in organic synthesis. The preparation of enantiomerically pure 4
      substituted quinolones.
AB  - 3,4-Dihydroquinolin-2(1H)-ones have potential biological and pharmacological
      significance. Enantiomerically pure benzothiazines, readily available via an
      intramolecular addition of a sulfoximine-stabilized carbanion to an alpha,beta
      unsaturated ester, could be used as templates for making a series of
      enantiomerically pure 3,4-dihydroquinolin-2(1H)-ones under mild conditions.

PMID- 17555326
TI  - Copper-catalyzed asymmetric reduction of 3,3-diarylacrylonitriles.
AB  - CuH-catalyzed enantioselective conjugate reduction of 3,3-diaryl-substituted
      acrylonitriles is described. A range of 3-aryl-3-pyridylacrylonitriles were
      reduced with high levels of enantioselectivity under optimal conditions employing
      a copper/Josiphos complex in the presence of polymethylhydrosiloxane (PMHS).

PMID- 17555327
TI  - Food-grade mulberry powder enriched with 1-deoxynojirimycin suppresses the
      elevation of postprandial blood glucose in humans.
AB  - Mulberry 1-deoxynojirimycin (DNJ), a potent glucosidase inhibitor, has been
      hypothesized to be beneficial for the suppression of abnormally high blood
      glucose levels and thereby prevention of diabetes mellitus. However, DNJ contents
      in commercial mulberry products were as low as about 0.1% (100 mg/100 g of dry
      product), implying that the bioavailability of DNJ might not be expected. We
      carried out studies in two directions: (1) production of food-grade mulberry
      powder containing a maximally high DNJ content; (2) determination of the optimal
      dose of the DNJ-enriched powder for the suppression of the postprandial blood
      glucose through clinical trials. The following method was used: (1) DNJ
      concentrations in mulberry leaves from different cultivars, harvest seasons, and
      leaf locations were determined using hydrophilic interaction chromatography with
      evaporative light scattering detection. (2) Healthy volunteers received 0, 0.4,
      0.8, and 1.2 g of DNJ-enriched powder (corresponding to 0, 6, 12, and 18 mg of
      DNJ, respectively), followed by 50 g of sucrose. Before and 30-180 min after the
      DNJ/sucrose administration, plasma glucose and insulin were determined. The
      following results were obtained: (1) Young mulberry leaves taken from the top
      part of the branches in summer contained the highest amount of DNJ. After
      optimization of the harvesting and drying processes for young mulberry leaves
      (Morus alba L. var. Shin ichinose), DNJ-enriched powder (1.5%) was produced. (2)
      A human study indicated that the single oral administration of 0.8 and 1.2 g of
      DNJ-enriched powder significantly suppressed the elevation of postprandial blood
      glucose and secretion of insulin, revealing the physiological impact of mulberry
      DNJ (effective dose and efficacy in humans). This study suggests that the newly
      developed DNJ-enriched powder can be used as a dietary supplement for preventing
      diabetes mellitus.

PMID- 17555328
TI  - Enzymatic production of xylooligosaccharides from cotton stalks.
AB  - Xylooligosaccharide (XO) production was performed from xylan, which was obtained
      by alkali extraction from cotton stalk, a major agricultural waste in Turkey.
      Enzymatic hydrolysis was selected to prevent byproduct formation such as xylose
      and furfural. Xylan was hydrolyzed using a commercial xylanase preparation, and
      the effects of pH, temperature, hydrolysis period, and substrate and enzyme
      concentrations on the XO yield and degree of polymerization (DP) were
      investigated. Cotton stalk contains about 21% xylan, the composition of which was
      determined as 84% xylose, 7% glucose, and 9% uronic acid after complete acid
      hydrolysis. XOs in the DP range of 2-7 (X6 approximately X5>X2>X3) were obtained
      with minor quantities of xylose in all of the hydrolysis conditions used.
      Although after 24 h of hydrolysis at 40 degrees C, the yield was about 53%, the
      XO production rate leveled off after 8-24 h of hydrolysis. XO yield was affected
      by all of the parameters investigated; however, none of them affected the DP of
      the end product significantly, except the hydrolysis period. Enzyme hydrolysis
      was maintained by the addition of fresh substrate after 72 h of hydrolysis,
      indicating the persistence of enzyme activity. The optimal hydrolysis conditions
      were determined as 40 degrees C, pH 5.4, and 2% xylan. The obtained product was
      fractionated via ultrafiltration by using 10, 3, and 1 kDa membranes. Complete
      removal of xylanase and unhydrolyzed xylan was achieved without losing any
      oligosaccharides having DP 5 or smaller by 10 kDa membrane. After a two-step
      membrane processing, a permeate containing mostly oligosaccharides was obtained.

PMID- 17555329
TI  - Hemoglobin-based O2 carrier O2 affinity and capillary inlet pO2 are important
      factors that influence O2 transport in a capillary.
AB  - Hemopure (Biopure; Cambridge, MA) and PolyHeme (Northfield Laboratories;
      Evanston, IL) are two acellular hemoglobin-based O2 carriers (HBOCs) currently in
      phase III clinical trials for use as red blood cell substitutes. The most common
      adverse side effect that these HBOCs exhibit is increased vasoconstriction.
      Autoregulatory theory has been presented as a possible explanation for this
      physiological effect, where it is hypothesized that low-affinity HBOCs over
      deliver O2 to tissues surrounding arterioles, thereby eliciting vasoconstriction.
      In this paper, we wanted to investigate HBOC oxygenation of tissue surrounding a
      capillary, which is the smallest element of the circulatory system. An a priori
      model has been developed in which the performance of mixtures of acellular HBOCs
      (synthesized by our group and others) and human red blood cells (hRBCs) has been
      simulated using a Krogh tissue cylinder model (KTCM) comprising a capillary
      surrounded by a capillary membrane and skeletal muscle tissue in cylindrical
      coordinates with specified tissue O2 consumption rates and Michaelis-Menten
      kinetics. In this study, the total hemoglobin (hRBCs and HBOCs) concentration was
      kept constant. The HBOCs studied possessed O2 affinities that were higher and
      lower compared to hRBCs (P50's spanned 5-55 mmHg), and the equilibrium
      binding/release of oxygen to/from the HBOCs was modeled using the Adair equation.
      At normoxic inlet pO2's, there was no correlation between O2 flux out of the
      capillary and the O2 affinity of the HBOC. However, a correlation was found
      between the average pO2 tension in the capillary and the O2 affinity of the HBOC.
      Additionally, we studied the change in the O2 equilibrium curve of HBOCs with
      different O2 affinities over a wide range of inlet pO2's and found that changing
      the inlet pO2 greatly affected which HBOC, having a unique O2 affinity, best
      delivered O2 to the surrounding tissue. The analysis of oxygen transport
      presented could lead to a better prediction of which acellular HBOC is best
      suited for a specific transfusion application that many times depends on the
      capillary inlet pO2 tension.

PMID- 17555330
TI  - High affinity of the cell-penetrating peptide HIV-1 Tat-PTD for DNA.
AB  - During cellular uptake of fluorescently labeled cell-penetrating peptides (CPPs),
      intense fluorescent signals are commonly observed in the nucleus of the cell,
      suggesting intracellular CPP relocation and potential binding to the genome of
      the host. We therefore investigated the interaction of the CPP HIV-1 Tat(47-57)
      with double-stranded DNA, and we also tested whether the fluorescence intensity
      of the labeled CPP allows for linear predictions of its intracellular
      concentration. Using isothermal titration calorimetry, we observe that the CPP
      has a high affinity for salmon sperm DNA as characterized by a microscopic
      dissociation constant of 126 nM. The binding is exothermic, with a reaction
      enthalpy of -4.63 kcal/mol CPP (28 degrees C). The dissociation constant and
      reaction enthalpy decrease further at higher temperatures. The affinity of the
      CPP for DNA is thus 1-2 magnitudes higher than for extracellular heparan sulfate,
      the likely mediator of the CPP uptake. Accordingly, the high affinity for DNA
      confers stability to extracellular transport complexes of CPP and DNA but
      potentially affects the regulation and molecular organization of the host's
      genome after nuclear uptake. Moreover, the CPP leads to the condensation of DNA
      as evidenced by the pronounced increase in light-scattering intensity. The
      fluorescence quantum yield of the FITC-labeled CPP decreases considerably at
      concentrations > 5 micromol/L, at pH < 7, and upon binding to DNA and
      glycosaminoglycans. This change in fluorescence quantum yield impedes the
      microscopic identification of uptake routes and the comparison of uptake
      efficiency of different CPPs, especially if the accumulation in subcellular
      compartments (self-quenching and pH difference) and transitory binding partners
      (quenching and condensation) is unknown.

PMID- 17555332
TI  - Mechanistic applicability domain classification of a local lymph node assay
      dataset for skin sensitization.
AB  - The goal of eliminating animal testing in the predictive identification of
      chemicals with the intrinsic ability to cause skin sensitization is an important
      target, the attainment of which has recently been brought into even sharper
      relief by the EU Cosmetics Directive and the requirements of the REACH
      legislation. Development of alternative methods requires that the chemicals used
      to evaluate and validate novel approaches comprise not only confirmed skin
      sensitizers and non-sensitizers but also substances that span the full chemical
      mechanistic spectrum associated with skin sensitization. To this end, a recently
      published database of more than 200 chemicals tested in the mouse local lymph
      node assay (LLNA) has been examined in relation to various chemical reaction
      mechanistic domains known to be associated with sensitization. It is demonstrated
      here that the dataset does cover the main reaction mechanistic domains. In
      addition, it is shown that assignment to a reaction mechanistic domain is a
      critical first step in a strategic approach to understanding, ultimately on a
      quantitative basis, how chemical properties influence the potency of skin
      sensitizing chemicals. This understanding is necessary if reliable non-animal
      approaches, including (quantitative) structure-activity relationships (Q)SARs,
      read-across, and experimental chemistry based models, are to be developed.

PMID- 17555331
TI  - Human p53 is inhibited by glutathionylation of cysteines present in the proximal
      DNA-binding domain during oxidative stress.
AB  - The cellular mechanisms that modulate the redox state of p53 tumor suppressor
      remain unclear, although its DNA binding function is known to be strongly
      inhibited by oxidative and nitrosative stresses. We show that human p53 is
      subjected to a new and reversible posttranslational modification, namely, S
      glutathionylation in stressed states, including DNA damage. First, a rapid and
      direct incorporation of biotinylated GSH or GSSG into the purified recombinant
      p53 protein was observed. The modified p53 had a significantly weakened ability
      to bind its consensus DNA sequence. Reciprocal immunoprecipitations and a GST
      overlay assay showed that p53 in tumor cells was marginally glutathionylated;
      however, the level of modification increased greatly after oxidant and DNA
      damaging treatments. GSH modification coexisted with the serine phophorylations
      in activated p53, and the thiol-conjugated protein was present in nuclei. When
      tumor cells treated with camptothecin or cisplatin were subsequently exposed to
      glutathione-enhancing agents, p53 underwent dethiolation accompanied by
      detectable increases in the level of p21waf1 expression, relative to the DNA
      damaging drugs alone. Mass spectrometry of GSH-modified p53 protein identified
      cysteines 124, 141, and 182, all present in the proximal DNA-binding domain, as
      the sites of glutathionylation. Biotinylated maleimide also reacted rapidly with
      Cys141, implying that this is the most reactive cysteine on the p53 surface. The
      glutathionylatable cysteines were found to exist in a negatively charged
      microenvironment in cellular p53. Molecular modeling studies located Cys124 and 
      141 at the dimer interface of p53 and showed glutathionylation of either residue
      would inhibit p53-DNA association and also interfere with protein dimerization.
      These results show for the first time that shielding of reactive cysteines
      contributes to a negative regulation for human p53 and imply that such an
      inactivation of the transcription factor may represent an acute defensive
      response with significant consequences for oncogenesis.

PMID- 17555333
TI  - Use of a polyhedral oligomeric silsesquioxane (POSS)-imidazolium cation as an
      organic modifier for montmorillonite.
AB  - Recent studies on organically modified clays (OMCs) have reported enhanced
      thermal stabilities when using imidazolium-based surfactants over the typical
      ammonium-based surfactants. Other studies have shown that polyhedral oligomeric
      silsesquioxanes (POSS) also improve the thermal properties of composites
      containing these macromers. In an attempt to utilize the beneficial properties of
      both imidazolium surfactants and POSS macromers, a dual nanocomposite approach to
      prepare OMCs was used. In this study, the preparation of a new POSS-imidazolium
      surfactant and its use as an organic modifier for montmorillonite are reported.
      The purity, solubility, and thermal characteristics of the POSS-imidazolium
      chloride were evaluated. In addition, several OMCs were prepared by exchanging
      the Na+ with POSS imidazolium cations equivalent to 100%, 95%, 40%, 20%, and 5%
      of the cation exchange capacity of the clay. The subsequent OMCs were
      characterized using thermal analysis techniques (DSC, SDT, and TGA) as well as
      29Si NMR to determine the POSS content in the clay interlayer both before and
      after thermal oxidation degradation. Results indicate the following: (1) the
      solvent choice changes the efficiency of the ion-exchange reaction of the clay;
      (2) self-assembled crystalline POSS domains are present in the clay interlayer;
      (3) the d-spacing of the exchanged clay is large (3.6 nm), accommodating a
      bilayer structure of the POSS-imidazolium; and (4) the prepared POSS-imidazolium
      exchanged clays exhibit higher thermal stabilities than any previously prepared
      imidazolium or ammonium exchanged montmorillonite.

PMID- 17555334
TI  - Selective intercalation of polymers in carbon nanotubes.
AB  - A room-temperature, open-air method is devised to selectively intercalate
      relatively low-molecular-weight polymers (approximately 10-100 kDa) from dilute,
      volatile solutions into open-end, as-grown, wettable carbon nanotubes with 50-100
      nm diameters. The method relies on a novel self-sustained diffusion mechanism
      driving polymers from dilute volatile solutions into carbon nanotubes and
      concentrating them there. Relatively low-molecular-weight polymers, such as
      poly(ethylene oxide) (PEO, 600 kDa) and poly(caprolactone) (PCL, 80 kDa), were
      encapsulated in graphitic nanotubes as confirmed by transmission electron
      microscopy, which revealed morphologies characteristic of mixtures in
      nanoconfinements affected by intermolecular forces. Whereas relatively small,
      flexible polymer molecules can conform to enter these nanotubes, larger
      macromolecules (approximately 1000 kDa) remain outside. The selective nature of
      this process is useful for filling nanotubes with polymers and could also be
      valuable in capping nanotubes.

PMID- 17555335
TI  - Investigation of the interaction force between Cryptosporidium parvum oocysts and
      solid surfaces.
AB  - Interaction force profiles between single Cryptosporidium parvum oocysts and
      positively charged, silane-coated silica particles were measured in aqueous
      solutions using an atomic force microscope. The oocysts were immobilized for the
      measurements by entrapment in Millipore polycarbonate membranes with 3 microm
      pore size. Experiments were performed in both NaCl and CaCl2 solutions at ionic
      strengths ranging from 1 to 100 mM. For both electrolytes, the decay length of
      the repulsive force profile was found to be nearly independent of the ionic
      strength and always much larger than the theoretical Debye length of the system.
      In addition, the magnitude of the force was found to be essentially the same for
      both electrolytes, suggesting that the long-range repulsive forces are primarily
      steric in nature. These results support the theory that the interaction force
      between oocysts and surfaces is controlled by an outer, weakly charged or
      uncharged carbohydrate layer. Measurements were also performed with oocysts that
      had been deactivated using either chemical (formalin) or heat treatment. The
      force profiles obtained with formalin-treated oocysts appear to be essentially
      the same as for the untreated oocysts, whereas the profiles measured with the
      heat-treated oocysts show a much stronger dependence on solution ionic strength.
      With either the heat-treated or formalin-treated oocysts, adhesion was observed
      much more frequently than with untreated oocysts, which is consistent with the
      increased deposition rate observed with treated oocysts by Kuznar and Elimelech
      (Kuznar, Z. A.; Elimelech, M. Langmuir 2005, 21, 710-716). These results also
      suggest that treated oocysts, especially ones that have been inactivated by
      heating, may not be good surrogates for viable oocysts in laboratory studies.

PMID- 17555336
TI  - Converting self-assembled gold nanoparticle/dendrimer nanodroplets into horseshoe
      like nanostructures by thermal annealing.
AB  - A simple and effective nonlithographic method to produce a novel organization of
      noble metal nanoparticles into horseshoe-like nanostructures via self-assembly is
      described. The adsorption of Au nanoparticles stabilized with the dendrimer
      1,2,3,4,5,6-hexakis[(3',5'-bis(benzyloxy)benzyl)sulfanylmethyl]benzene (S(6)G(1))
      on hydrophilic surfaces (native oxide-terminated Si(111)) resulted in the
      formation of spatially correlated droplet aggregates. Annealing of Au/S(6)G(1) in
      thin films caused amalgamated droplets to form arrays of horseshoe-like
      nanostructures with an average size of approximately 250 nm and an average height
      of 13 nm. The mobility and the manner in which the semicapped Au nanoparticles
      are distributed on the hydrophilic substrate are believed to be the promoters
      that control the growth of the nucleation to create the horseshoe-like
      structures. Atomic force microscopy (AFM) measurements demonstrated the changes
      in height and size of the nanoparticles before and after the annealing process.
      Oxygen plasma etching was used to remove the S(6)G(1) dendrimer to reveal the
      orientation of the Au nanocrystals in the nanostructure matrix.

PMID- 17555337
TI  - Layer-by-layer deposited organic/inorganic hybrid multilayer films containing
      noncentrosymmetrically orientated azobenzene chromophores.
AB  - Organic/inorganic hybrid multilayer films with noncentrosymmetrically orientated
      azobenzene chromophores were fabricated by the sequential deposition of ZrO2
      layers by a surface sol-gel process and subsequent layer-by-layer (LbL)
      adsorption of the nonlinear optical (NLO)-active azobenzene-containing polyanion
      PAC-azoBNS and poly(diallyldimethylammonium chloride) (PDDA). Noncentrosymmetric
      orientation of the NLO-active azobenzene chromophores was achieved because of the
      strong repulsion between the negatively charged ZrO(2) and the sulfonate groups
      of the azobenzene chromophore in PAC-azoBNS. Regular deposition of ZrO(2)/PAC
      azoBNS/PDDA multilayer films was verified by UV-vis absorption spectroscopy and
      quartz crystal microbalance measurements. Both UV-vis absorption spectroscopy and
      transmission second harmonic generation (SHG) measurements confirmed the
      noncentrosymmetric orientation of the azobenzene chromophores in the as-prepared
      ZrO2/PAC-azoBNS/PDDA multilayer films. The square root of the SHG signal
      (I(2omega)(1/2)) increases with the increase of the azobenzene graft ratio in PAC
      azoBNS as the number of deposition cycles of the ZrO(2)/PAC-azoBNS/PDDA films
      remains the same, while the second-order susceptibility chi(zzz)(2) of the film
      decreases with the increase of the azobenzene graft ratio. Furthermore, the
      present method was successfully extended to realize the noncentrosymmetric
      orientation of azobenzene chromophores in multilayer films when small organic
      azobenzene compounds with carboxylic acid and/or hydroxyl groups at one end and
      sulfonate groups at the other end were used. The present method was characterized
      by its simplicity and flexibility in film preparation, and it is anticipated to
      be a facile way to fabricate second-order nonlinear optical film materials.

PMID- 17555338
TI  - Surface properties of "jellyfish": Langmuir monolayer and Langmuir-Blodgett film
      studies of recombinant aequorin.
AB  - In this paper, we studied the surface properties of recombinant aequorin at the
      air-water interface. Using the Langmuir monolayer technique, the surface
      properties of aequorin were studied, including the surface pressure and surface
      potential-area isotherms, compression-decompression cycles, and stability on
      Trizma Base (Tris/HCl) buffer at pH 7.6. The results showed that aequorin formed
      a stable Langmuir monolayer and the surface pressure-area isotherms were
      dependent on both pH and ionic strength. At a pH higher or lower than 7.6, the
      limiting molecular area decreased. The circular dichroism (CD) spectra of
      aequorin in aqueous solutions explained this result: when the pH was higher than
      7.6, the alpha-helix conformation changed to unordered structures, whereas at a
      pH lower than 7.6, the alpha-helix conformation changed to beta-sheet. The
      addition of calcium chloride to the Tris/HCl buffer subphase (pH 7.6) caused an
      increase of the limiting molecular area of the aequorin Langmuir monolayer. The
      fluorescence spectra of a Langmuir-Blodgett (LB) film of aequorin in the presence
      of calcium chloride indicated that the aequorin transformed to the apoaequorin.

PMID- 17555339
TI  - Cationic lipid absorption on titanium: a counterion-mediated bilayer-to-lipid
      tubule-network transition.
AB  - By carefully tuning the screening effects of monovalent salt in solution, it is
      possible to control the formation of different lipid morphologies on a titanium
      dioxide substrate. A transition from an absorbed vesicle layer to fluid lipid
      bilayers is observed as a function of monovalent salt concentration in solution,
      and, above a threshold salt concentration, a network of lipid tubules with a
      fascinating distorted-hexagonal structure is formed in two dimensions on the
      substrate. We present fluorescence microscopy data for these different
      morphologies, confirming the connectivity and fluidity of the bilayers and
      tubules.

PMID- 17555340
TI  - Relationship between vitamin D binding protein and aspirin resistance in coronary
      ischemic patients: a proteomic study.
AB  - Our aim was to analyze the plasma proteome in aspirin (acetylsalicylic acid
      [ASA])-sensitive and ASA-resistant coronary ischemic patients. Plasma from 19 ASA
      sensitive and 19 ASA-resistant patients was analyzed. For the proteomic study,
      two-dimensional electrophoresis was performed. The expression of one isotype of
      the fibrinogen gamma chain and three isotypes of haptoglobin was increased in ASA
      resistant patients. Three vitamin D binding protein isotypes were increased in
      ASA-resistant patients. In vitro incubation of vitamin D binding protein (DBP)
      with blood from healthy volunteers reduced the inhibitory effect of ASA on
      thromboxane A2 production. DBP may be a new regulator of the inhibitory effect of
      ASA on platelets.

PMID- 17555342
TI  - "Non-evaporating" microdroplets on self-assembled monolayer surfaces under
      ambient conditions.
AB  - A unique "non-evaporation" phenomenon, i.e., the unusually slow evaporation
      process of sessile microdroplets on self-assembled monolayer (SAM) surfaces, is
      reported. It has been observed that only droplets containing a certain proportion
      of a volatile and a less-volatile component undergo non-evaporation, which is
      characterized by hours-long existence of the droplets maintaining constant
      contact angle, contact area, and volume. We propose that for alcohol-water binary
      mixtures on SAM surfaces, the highly orientated and closely packed hydrophobic 1
      decanethiol molecules induce a concentration gradient of alcohol in water, with a
      higher concentration of alcohol near the SAM surface. Initial evaporation of the
      alcohol (more volatile) increased the contact angle until the establishment of a
      new composition, which contains a strong hydrogen-bonding network among the water
      molecules in the presence of the alcohol alkyl chains. There is a lessened
      tendency for the alcohol to evaporate in the presence of a concentration gradient
      due to such interactions, which results in the observed "non-evaporating"
      phenomenon. This type of unusual evaporating profile was not observed on
      conventional substrates, such as polycarbonate sheets and microscope glass slides
      modified with alkyltrichlorosilanes.

PMID- 17555341
TI  - Wide scale range structure in polyelectrolyte-protein dense complexes: where Sans
      meets freeze-fracture microscopy.
AB  - We show in this paper how the combination of SANS and freeze-fracture electron
      microscopy (FFEM) is a powerful tool to picture the structure of very turbid
      sample liquids at spatial scales lying from a few A to several microns. In a
      given range of chain size and species concentrations, primary complexes in the
      shape of globules are observed by both techniques. SANS allows a precise
      quantitation of size, inner structure, and composition of these globules, as well
      as aggregated structure of the globules at larger scales, which is fractal-like,
      with a Hausdorff dimension 2.1 characteristic of Reaction Limited Aggregation
      (RCLA). The existence of aggregates is seen by FFEM, but most of all FFEM shows
      the lack of any further structure at larger scale, up to the micrometer size.

PMID- 17555343
TI  - Adsorption of polyelectrolyte versus surface charge: in situ single-molecule
      atomic force microscopy experiments on similarly, oppositely, and heterogeneously
      charged surfaces.
AB  - We have studied the effect of the pH and surface charge of mica on the adsorption
      of the positively charged weak polyelectrolyte (PE) poly(2-vinylpyridine) (P2VP)
      using atomic force microscopy (AFM) single-molecule experiments. These AFM
      experiments were performed in situ directly under aqueous media. If the mica's
      surface and the PE are oppositely charged (pH > 3), the PE forms a flat adsorbed
      layer of two-dimensionally (2D) equilibrated self-avoiding random walk coils. The
      adsorbed layer's structure remains almost unchanged if the pH is decreased to pH
      3 (the mica's surface is weakly charged). At pH 2 (the mica surface is decorated
      by spots of different electrical charges), the polyelectrolyte chains take the
      form of a 2D compressed coil. In this pH range, at an increased P2VP
      concentration in solution, the PE segments preferentially adsorb onto the top of
      previously adsorbed segments, rather than onto an unoccupied surface. We explain
      this behavior as being caused by the heterogeneous character of the charged
      surface and the competitive adsorption of hydronium ions. The further increase of
      polymer concentration results in a complete coverage of the mica substrate and
      the charge overcompensation by P2VP chains adsorbed on the similarly charged
      substrate, due to van der Waals forces.

PMID- 17555344
TI  - Helical packing of discotic hexaphenyl hexa-peri-hexabenzocoronenes: theory and
      experiment.
AB  - The arrangement of discotic hexa-peri-hexabenzocoronenes (HBCs) into columnar
      helical superstructures has been investigated in relation to their molecular
      architecture. The supramolecular structure of two hexaphenyl-substituted HBC
      derivatives, differing only in the chiral/achiral nature of the attached alkyl
      side chains, was studied by circular dichroism and temperature-dependent wide
      angle X-ray diffraction on oriented filaments. A structural model in agreement
      with the experimental observations was developed on the basis of accompanying
      quantum-chemical calculations. The helical organization along the self-assembled
      columnar structures was induced by the steric requirements of the bulky phenyl
      rings near the aromatic core, i.e., by their rotation out-of-plane with respect
      to the aromatic core. On the other hand, a uniform handedness of the twist was
      generated by chiral alkyl substituents. At higher temperatures the degree of
      helical organization decreases due to lateral and longitudinal dynamics of the
      discotic molecules. Annealing at ambient conditions improved the long-range
      arrangement of the discs along the columnar structures. This reorganization
      indicated a self-healing of the plastic material which is desirable for
      application of discotics as active layers in electronic devices. The helical
      packing resulted in a considerable stability of the mesophase up to 500 degrees
      C, which has not been reported for a discotic so far.

PMID- 17555345
TI  - Dependency of particle sizes and colloidal stability of polyelectrolyte complex
      dispersions on polyanion structure and preparation mode investigated by dynamic
      light scattering and atomic force microscopy.
AB  - Polyelectrolyte complex (PEC) dispersions were prepared by controlled mixing of
      three random copolymers of sodium 2-acrylamido-2-methylpropanesulfonate (AMPS)
      with either t-butyl acrylamide (TBA) [P(AMPS54-co-TBA46) and P(AMPS37-co-TBA63)]
      or methyl methacrylate (MM) [P(AMPS52-co-MM48)] with an ionene-type polycation,
      containing 95 mol % N,N-dimethyl-2-hydroxypropyleneammonium chloride repeat units
      (PCA5), with their structural characteristics being deeply investigated by
      dynamic light scattering (DLS) and atomic force microscopy (AFM). Shape, size,
      and polydispersity of the PEC dispersions were directly observed by AFM as a
      function of polyanion structure, the ratio between charges, n-/n+, and the
      titrant addition rate (TAR). The particle sizes increased and the colloidal
      stability decreased with the increase of the nonionic comonomer content and with
      the decrease of TAR. It was demonstrated that the medium particle sizes of the
      complex nanoparticles adsorbed on silicon wafers measured by AFM, in the dry
      state, were close but always lower than those measured by DLS, both before and
      after the complex stoichiometry.

PMID- 17555346
TI  - Roles of diffusion and activation barrier on the appearance of Marcus inversion
      behavior: a study of a photoinduced electron-transfer reaction in aqueous
      triblock copolymer (p123) micellar solutions.
AB  - Photoinduced electron transfer (ET) reactions between amines and a series of
      coumarins have been investigated using fluorescence-quenching measurements in
      aqueous P123 triblock copolymer micellar solutions. Fluorescence spectral
      characteristics and fluorescence anisotropy measurements indicated a nearly
      similar microenvironment for all of the coumarins used in P123 micelles.
      Substantial quenching of coumarin fluorescence in the presence of amines has been
      observed. The quenching rates (k(q)(TR)) are largely reduced in the P123 micelle
      as compared to those in other micelles (sodium dodecyl sulfate (SDS), Triton-X
      100 (TX-100), cetyl trimethyl ammonium bromide (CTAB), and dodecyl trimethyl
      ammonium bromide (DTAB)), which is probably due to larger coumarin-amine
      separations in the micellar phase. The k(q)(TR) values, when plotted against free
      energy changes (DeltaG degrees), follow a Marcus predicted bell-shaped
      correlation. The estimated activation energy for the ET reactions follow an
      inverse bell-shaped correlation with DeltaG degrees. Present results indicate
      that the appearance of Marcus inversion is primarily related to the changes in
      the activation barrier, as predicted from the Marcus ET theory. As the k(q)(TR)
      values are higher than the estimated bimolecular diffusional rate constant, the
      role of reactant diffusion on the quenching kinetics in the P123 micelle is
      negligible. The appearance of Marcus inversion at unexpectedly lower exergonicity
      has been rationalized on the basis of slow solvent relaxation and by the
      application of the two-dimensional ET (2DET) theory. Critical analysis of the
      present results establishes that the inversion in the ET rates at high
      exergonicity is not due to the alteration in the diffusion parameters of the
      reactants, as has been suggested in some recent reports. Instead, it is evident
      that the inversion in quenching rates at high exergonicity is due to the
      alteration in the activation barrier for the ET reactions.

PMID- 17555347
TI  - Time-resolved synchrotron XPS monitoring of irradiation-induced nitrobenzene
      reduction for chemical lithography.
AB  - The irradiation-induced reduction of electrochemically grafted nitrobenzene films
      on Si(111) was monitored by high-resolution photoelectron spectroscopy. The
      experiments were performed using synchrotron soft X-ray irradiation at the BESSY
      II synchrotron facility. The evolution of different chemical species was
      monitored as a function of time. Careful fitting of the Si2p, C1s, N1s, and O1s
      core level spectra allowed us to follow this process in detail and to determine
      the constants of growth and decay of the specific components. The chemical
      changes were caused by the X-ray irradiation-induced secondary electron current
      through the aryl layer. A minor fraction (approximately 25%) of the initial nitro
      groups was split off and desorbed. The bulk of the NO2 groups was reduced to
      species in an amino-like chemical environment. A desorption of carbon fragments
      was not observed, and benzene ring specific shakeup satellites indicated that the
      aromatic ring structure remained intact. Irradiation-induced line-shape changes
      suggest a polymerization via -NH- bridges, which were formed after the
      irradiation-induced N-O bond splitting. A significant part of the released oxygen
      appeared to contribute to an oxidation of the silicon substrate at the
      Si(111)/benzene interface. The irradiation-induced aryl layer modification can be
      exploited for chemical lithography (i.e., a lateral structuring of functionalized
      silicon surfaces).

PMID- 17555348
TI  - Two-dimensional chiral single domain by D-alaninol functionalization of Cu(100).
AB  - We report the results of chemisorption in saturating conditions of D-alaninol on
      Cu(100) in term of the analysis of low-energy electron diffraction and scanning
      tunneling microscopy data. A large two-dimensional, single domain, ordered chiral
      structure of quadrangular tetrameric molecular units is formed. The four
      molecules interact differently with the surface in the two orthogonal directions.

PMID- 17555349
TI  - Indole alkaloids produced by a marine fungus isolate of Penicillium janthinellum
      Biourge.
AB  - Three new indole alkaloids, shearinines D, E, and F (1-3), together with the
      known shearinine A (4) were isolated from the marine-derived strain of the fungus
      Penicillium janthinellum Biourge. The chemical structures of 1-4 were established
      by 2D NMR and HREIMS data. Shearinines A, D, and E induce apoptosis in human
      leukemia HL-60 cells, and shearinine E also inhibits EGF-induced malignant
      transformation of JB6 P+ Cl 41 cells in a soft agar.

PMID- 17555350
TI  - Terpenoids from the medicinal plant Maytenus ilicifolia.
AB  - Four new terpenoids (1-4) were isolated from the root bark of Maytenus
      ilicifolia. Their structures were determined by spectroscopic studies, and
      complete 1H and 13C NMR assignments were achieved by 2D NMR spectroscopy. We also
      report an efficient method for the separation of quinonemethide triterpenes based
      on centrifugal partition chromatography.

PMID- 17555351
TI  - Chlorination diversifies Cimicifuga racemosa triterpene glycosides.
AB  - Extracts from the roots and rhizomes of black cohosh (Cimicifuga racemosa) are
      widely used as dietary supplements to alleviate menopausal symptoms. State-of-the
      art quality control measures involve phytochemical fingerprinting of the
      triterpene glycosides for species identification and chemical standardization by
      HPLC. In the course of developing materials and methods for standardization
      procedures, the major C. racemosa triterpene glycoside (1) was isolated and
      initially thought to be cimicifugoside (2). Detailed HR-LC-MS and 1D and 2D NMR
      analysis of 1 and 2 unambiguously revealed that 1 is the chlorine-containing
      derivative of 2, namely, 25-chlorodeoxycimigenol-3-O-beta-d-xyloside.
      Accordingly, HPLC profiles of black cohosh preparations require revision of the
      assignments of the chlorinated (1) and nonchlorinated (2) pair. Besides
      explaining the substantial shift in polarity (DeltatR[RP-18] ca. 20 min), 25
      deoxychlorination opens a new pathway of structural diversification in triterpene
      glycoside chemistry. As chemical conversion of 2 into 1 could be demonstrated,
      deoxychlorination may be interpreted as artifact formation. Simultaneously,
      however, it is a potentially significant pathway for the gastric in vivo
      conversion ("nature's prodrug") of the relatively polar triterpene glycosides
      into significantly less polar chlorinated derivatives with altered
      pharmacological properties.

PMID- 17555352
TI  - Fluorescent pyrimidopyrimidoindole nucleosides: control of photophysical
      characterizations by substituent effects.
AB  - 10-(2-Deoxy-beta-D-ribofuranosyl)pyrimido[4',5':4,5]pyrimido[1,6-a]indole-6,9(7H)
      dione (dCPPI) and its derivatives were synthesized via the Suzuki-Miyaura
      coupling reaction of 5-iododeoxycytidine with 5-substituted N-Boc-indole-2
      borates and characterized by UV-vis and fluorescence spectroscopy. The new
      fluorescent nucleosides showed rather large Stokes shifts (116-139 nm) in an
      aqueous buffer. The fluorescent intensities were dependent on the nature of the
      substituents on the indole rings. The electron-withdrawing groups increased the
      fluorescent intensity while the electron-donating groups having lone pairs
      decreased it. Among the substituted dCPPI derivatives tested, the
      trimethylammonium derivative of dCPPI was found to emit the brightest fluorescent
      light. The solvatochromism of dCPPI and its derivatives was also studied. Some of
      the dCPPI derivatives showed interesting solvent-dependent fluorescence
      enhancement and could be useful as new fluorescent structural probes for nucleic
      acids. The Lippert-Mataga analyses of the Stokes shift were also carried out to
      obtain estimated values of the dipole moment of the excited states of some of the
      derivatives.

PMID- 17555353
TI  - Total synthesis and biological evaluation of tamandarin B analogues.
AB  - Tamandarins A and B are a class of marine natural cyclodepsipeptides with
      structures and biological activities closely related to those of the didemnins.
      The easier synthetic access to tamandarins accelerates the preparation of new
      macrocyclic derivatives of this family of antitumor, antiviral, and
      immunosuppressive compounds. The optimization of the previously reported
      synthetic route to tamandarins by changing the macrolactamization site from Nst1
      and Thr6 to Pro4 and N,O-Me2Tyr5 residues led to a significant improvement in the
      reaction yield. Using this new synthetic approach, four new macrocyclic analogues
      of tamandarin B were prepared and evaluated for anticancer activity. These
      results provide further insight into the structure-activity relationship of the
      tamandarins and didemnins.

PMID- 17555354
TI  - An Asymmetric, bifunctional catalytic approach to non-natural alpha-amino acid
      derivatives.
AB  - A catalytic, asymmetric process for the synthesis of 1,4-benzoxazinones from o
      benzoquinone imides and ketene enolates is reported. Addition of Lewis acids
      (Zn(OTf)2, In(OTf)3, and in particular Sc(OTf)3) creates a bifunctional catalytic
      system that dramatically increases the reaction rate and the yield of these non
      natural amino acid precursors while preserving the remarkable enantioselectivity
      inherent to the reaction. Cocatalyst Sc(OTf)3 increases the yield by up to 42%
      while producing products in >99% ee.

PMID- 17555355
TI  - Metal triflate-catalyzed cationic benzylation and allylation of 1,3-dicarbonyl
      compounds.
AB  - The rare earth metal and hafnium triflate-catalyzed secondary benzylation and
      allylation of 1,3-diketones, ketoesters, and ketoamides are described. The
      procedure was carried out under non-anhydrous conditions. Various 1-phenylethyl
      cations were generated from substituted 1-phenylethanols using 0.5 mol % of the
      metal triflates in CH3NO2. The cations reacted with 1,3-diketones and ketoesters
      to give benzylated products in high yields. Following the GC analysis, the
      reaction conditions were easily optimized by the selection of catalysts based on
      the Lewis acidity of the triflates and reaction temperature. A tertiary-alkylated
      diketone and a corresponding ketoester were also benzylated to afford products
      with a quaternary carbon atom in 57-84% yield. The ketoamide reactions required
      stronger Lewis acids than those used in the diketone and ketoester reactions. The
      reactions of benzylic alcohols possessing various substituents on the aromatic
      ring and dibenzoylmethane (2b) as a diketone were examined in the presence of
      Hf(OTf)4. Electron-rich benzylic alcohols reacted with 2b in 86-96% yield, and
      electron-deficient alcohol gave the desired product in 79-65% yield. Despite
      possessing a strong electron-withdrawing group, the reaction of 1-(4
      nitrophenyl)ethanol gave the corresponding product in 61% yield. It was also
      possible to use allylic alcohols directly for the allylation of diketone 2b. The
      catalyst can be recovered by water extraction and reused up to five times.

PMID- 17555356
TI  - Morita-Baylis-Hillman reaction of masked 5-alkylidene-2-cyclopentenones: general
      entry to 5-alkylidene-2-(hydroxyalkyl)- 2-cyclopentenones.
AB  - The reaction of masked 5-alkylidene-2-cyclopentenones with aldehydes catalyzed by
      tributylphosphine in the presence of phenol provided the corresponding Morita
      Baylis-Hillman adducts, which were subjected to flash vacuum pyrolysis to afford
      5-alkylidene-2-(hydroxyalkyl)-2-cyclopentenones.

PMID- 17555357
TI  - Synthesis of indolo[1,2-f]phenanthridines from palladium-catalyzed reactions of
      arynes.
AB  - A novel convenient approach for the construction of indolo[1,2-f]phenanthridine
      was developed from the reaction of arynes with 1-(2-bromophenyl)-1H-indole in the
      presence of palladium catalyst.

PMID- 17555358
TI  - Role of the countercation in diastereoselective alkylations of pyramidalized
      bicyclic serine enolates. An easy approach to alpha-benzylserine.
AB  - The use of a chiral serine equivalent as an excellent chiral building block has
      been demonstrated in the synthesis of alpha-benzylserine through a
      diastereoselective lithium enolate alkylation reaction and subsequent acid
      hydrolysis. The role of a coordinating countercation (lithium) in the alkylation
      reaction has been investigated. Theoretical studies have been performed in order
      to elucidate the stereochemical outcome of the alkylation process, which occurs
      with total retention of configuration.

PMID- 17555360
TI  - Synthesis of 4-iodo-3-furanones utilizing electrophile-induced tandem
      cyclization/1,2-migration reactions.
AB  - Two protocols for the construction of 4-iodo-3-furanones through a sequence
      consisting of cyclization and 1,2-migration of 2-alkynyl-2-silyloxy carbonyl
      compounds were developed. In one, electrophilic cyclization is directly induced
      by N-iodosuccinimide (NIS). In the second less limited variant, AuCl3 catalyzes
      the tandem reaction in the presence of NIS to provide highly substituted
      heterocycles in moderate to excellent yields.

PMID- 17555359
TI  - Toward the total synthesis of FR901483: concise synthesis of the azatricyclic
      skeleton.
AB  - A concise synthesis of the azatricyclic core of FR901483 has been accomplished
      using a novel strategy that involves a nucleophilic addition to an N-acyl iminium
      ion, a ring-closing metathesis, a diastereoselective hydroboration, and a lactone
      lactam rearrangement that worked well in a preliminary model study. Extension of
      this approach to the synthesis of a more highly functionalized intermediate that
      could be transformed into (-)-FR901483 first required the development of a new
      protecting group, the 1-ethylallyloxycarbamate group, for amines that may be
      removed under mild conditions. However, because the stereoselectivity in a key
      step in which a functionalized allyl zinc reagent was added to an intermediate
      hydroxy-substituted imine was low, this route to (-)-FR901483 is no longer being
      pursued.

PMID- 17555361
TI  - Facile, mild, and highly enantioselective alkynylzinc addition to aromatic
      aldehydes by BINOL/N-methylimidazole dual catalysis.
AB  - The dual Lewis acid/base catalytic system, generated from N-methylimidazole
      (NMI), (R)-1,1'-bi-2-naphthol [(R)-BINOL], and Ti(OiPr)4, effectively catalyzes
      the enantioselective alkynylation of aldehydes in the presence of Et2Zn in good
      yields and excellent enantioselectivities of up to 94% ee at room temperature.
      The mild reaction conditions make it possible to use functional alkynes in this
      asymmetric addition.

PMID- 17555362
TI  - Short and efficient asymmetric synthesis of (-)-alpha-conhydrine.
AB  - The short and efficient synthesis of (-)-alpha-conhydrine was accomplished with
      41% overall yield in seven steps and high diastereo- and enantioselectivity. The
      anti-stereochemistry of the two stereogenic centers has been confirmed by the
      single-crystal X-ray analysis of an intermediate.

PMID- 17555363
TI  - Ultralow feeding gas flow guiding growth of large-scale horizontally aligned
      single-walled carbon nanotube arrays.
AB  - On the basis of the rational analysis about the fluidic property of the system,
      an ultralow gas flow chemical vapor deposition (CVD) strategy was designed to
      prepare large-scale horizontally aligned ultralong single-walled carbon nanotube
      (SWNT) arrays. SWNT arrays could be well obtained under extremely low feeding
      flow of 1.5 sccm in a 1 in. quartz tube reactor. It was confirmed that the tubes
      grew floatingly and could cross microtrenches or climb over micro-obstacles in
      ultraslow gas flow. SWNTs arrays also could be formed no matter the substrate was
      placed vertically or upside down. The growth mechanism was discussed. Both the
      buoyancy effect induced by gas temperature/density difference and gas flow
      stability played dominant roles. More attractively, simultaneous batch-scale
      preparation of SWNT arrays was realized by the ultralow gas flow strategy. This
      new strategy turns to be more abstemious, efficient, promising, and flexible
      compared with the high gas flow rate fast-heating CVD processes.

PMID- 17555364
TI  - Prostacyclin in liver disease: a potential therapeutic option.
AB  - Complex molecular and cellular mechanisms are involved in the initiation and
      progression of hepatic fibrosis. Recent studies have shown that hepatic stellate
      cells, endothelin, cytokines and prostacyclin play crucial roles in this
      pathology. Prostacyclin exerts vasorelaxant, antioxidant and antifibrotic
      properties that prevent the development of fibrosis and cirrhosis in liver
      diseases. In this editorial, the authors discuss some of the molecular and
      cellular mechanisms involved in the initiation and progression of liver fibrosis
      and the role played by prostacyclin in counteracting it. At the moment, however,
      only limited information is available from clinical studies demonstrating the
      effectiveness of prostacyclin in liver diseases and this makes it difficult to
      draw any conclusions; further efforts are necessary to verify whether
      prostacyclin, alone or in combination with other drugs, may be a valid
      therapeutic option in liver diseases.

PMID- 17555365
TI  - Adult stem cells for cardiovascular diseases: the adipose tissue potential.
AB  - Cardiovascular diseases, as well as cardiac ischemia and lower limb
      vascularization, are associated with obesity and Type II diabetes, and pose a
      major public health problem. Recent advances in understanding stem cell biology
      have prompted the initiation of clinical trials of cardiac and vascular cell
      therapy. Autologous adult stem cells are generally taken from bone marrow or
      circulating blood. Although significant and encouraging results have been
      obtained in human studies where these cells have been employed, obtaining
      sufficient numbers of these cells is a major constraint. Recent studies have
      identified adipose tissue as a new source of stem cells; some of which may be
      suitable for the restoration of cardiovascular function. As lipoaspiration
      provides relatively simple access to this stem cell pool, and with the very large
      numbers of cells present in adipose tissue, its future potential as a stem cell
      reservoir for cardiovascular cell therapy is promising.

PMID- 17555366
TI  - Non-viral gene delivery: from the needle to the nucleus.
AB  - Despite nearly two decades of research, the successful application of
      systemically delivered non-viral gene therapies to treat human disease is still
      limited by poor transfection efficiency. The major barriers in the circulation
      and in the cell that limit transfection efficiency have been identified and the
      field has entered a phase of design and testing of more sophisticated carrier
      systems that attempt to circumvent these barriers. These studies are increasingly
      conducted in vivo using rapid quantitative measures of gene transfer efficiency
      as a guide. Although there has been steady progress in developing DNA
      nanoparticles that navigate the circulation, enter the target cell and escape
      lysosomal targeting, the final goal of efficiently traversing the nuclear
      membrane remains the most significant challenge. The ultimate goal is to develop
      elegant delivery systems that work in concert to deliver DNA from the needle to
      the nucleus.

PMID- 17555367
TI  - Novel vectors for in vivo gene delivery to vascular tissue.
AB  - Although some success has been achieved with gene delivery in animal models of
      vascular disorders, the results from some clinical trials have been less
      promising, possibly due, in part, to the use of suboptimal vectors for in vivo
      gene transfer. Non-viral vectors have a very low transfection efficiency so are
      largely unsuitable for most in vivo applications, and the relatively broad
      tropism of many of the commonly used viral vectors can limit efficient gene
      delivery specifically to target vascular tissues. However, characterisation of
      novel virus serotypes and advances in techniques that enable vectors to be
      targeted to the required tissue have led to progress in the development of novel
      vectors that could be utilised for gene delivery for vascular disorders.

PMID- 17555368
TI  - Her signaling in pancreatic cancer.
AB  - Pancreatic cancer remains a treatment-refractory cancer. Standard therapy for
      metastatic cancer is gemcitabine chemotherapy, with a median survival of 5-6
      months. The epidermal growth factor receptor (EGFR) is commonly expressed in
      pancreatic cancer and has been evaluated as a therapeutic target. A Phase III
      trial of gemcitabine with or without the EGFR inhibitor, erlotinib, demonstrated
      a modest but significant prolongation of survival with the addition of erlotinib.
      A Phase II trial of gemcitabine with the anti-EGFR antibody cetuximab resulted in
      a 1-year survival of 32%. A Phase III trial of gemcitabine with or without
      cetuximab and a randomized Phase II trial of the Murren regimen with or without
      cetuximab are completed; results for both are anticipated in 2007. A Phase I
      trial of gemcitabine with the EGFR/Her-2 inhibitor, lapatinib, is completed.
      Improved patient selection and rational combination of targeted therapies will be
      necessary to optimize the management of patients with this tragic disease.

PMID- 17555369
TI  - Potential of oligonucleotide-mediated exon-skipping therapy for Duchenne muscular
      dystrophy.
AB  - Many of the mutations associated with Duchenne muscular dystrophy can potentially
      be rescued by exon-skipping therapy, targeting selected exons of prespliced mRNA
      for the dystrophin gene with antisense oligonucleotides, thereby restoring
      reading frames. The recent development of antisense oligonucleotides with higher
      stability and lower toxicity, such as morpholinos, has made it possible to
      restore dystrophin efficiently in dystrophic mice in vivo with no obvious side
      effects. There seems little doubt that such exon-skipping therapy is destined to
      proceed to the clinical application stage in patients with Duchenne muscular
      dystrophy. One of the remaining issues to be addressed is the skipping of
      multiple exons because such multi-exon skipping therapy could expand the
      potential patient target population to include 80% of those with duplication
      mutations and 90% of those with deletion mutations. At present, this multi-exon
      skipping strategy is being investigated in dystrophic dogs as well as dystrophic
      mice. There are several challenges that still need to be overcome, including the
      low uptake of antisense oligonucleotides into the heart and the need to design
      efficient, nontoxic, cost-effective oligonucleotides. This review summarizes
      recent progress in exon-skipping therapy and discusses future perspectives with
      regard to human clinical trials.

PMID- 17555370
TI  - New insights into the pathogenesis and treatment of anthrax toxin-induced shock.
AB  - Inhalational Bacillus anthracis infection is a leading bioterrorist health threat
      in the US today. Lethal (LeTx) and edema toxin production are key to the virulent
      effects of this lethal bacteria. Recent insights into the structure and function
      of these toxins have increased the understanding of both the pathogenesis and
      treatment of anthrax. These are binary type toxins comprised of protective
      antigen necessary for their cellular uptake and either lethal or edema factors,
      the toxigenic moieties. Primary cellular receptors for protective antigen have
      been identified and the processing of the completed toxins clarified. Consistent
      with the ability of lethal factor to cleave mitogen activated protein kinase
      kinases, the evidence indicates that an excessive inflammatory response does not
      contribute to shock with LeTx. Rather, the immunosuppressive effects of LeTx
      could promote infection; however, direct endothelial dysfunction may have an
      important role in shock due to LeTx. Recent studies show that edema factor, a
      potent adenyl cyclase, may have a major role in shock during anthrax and that it
      may also be immunosuppresive. Therapies under development which target several
      steps in the cellular uptake and function of these two toxins have been effective
      in both in vitro and in vivo systems. Understanding how best to apply these
      agents in combination with conventional treatments should be a goal of future
      research.

PMID- 17555371
TI  - Effects of anticoagulant strategies on activation of inflammation and
      coagulation.
AB  - Acute inflammatory events, such as those that occur in sepsis, lead to
      dysregulation of the coagulation cascade. The hemostatic imbalance in sepsis,
      characterized by the excessive activation of procoagulant pathways and the
      impairment of anticoagulant activity, leads to disseminated intravascular
      coagulation and results in microvascular thrombosis, tissue hypoperfusion and,
      ultimately, multiple organ failure and death. Furthermore, natural anti
      inflammatory mechanisms of the endogenous anticoagulants are diminished by the
      impaired coagulation. Supportive strategies aiming at inhibiting activation of
      coagulation and inflammation by treatment with exogenous anticoagulants have been
      found to be beneficial in experimental and initial clinical studies. This review
      summarizes the available experimental and clinical data regarding the interaction
      between coagulation and inflammation, focusing on the two anticoagulants which
      are in clinical use, antithrombin and activated protein C. Identification of the
      different biological mechanisms of the two endogenous anticoagulants might help
      to determine target patient populations as well as to develop new anticoagulant
      analogs that differ in there respective effects in coagulation and inflammation.

PMID- 17555372
TI  - The developing trend of monoclonal antibodies in the treatment of colorectal
      cancer.
AB  - Monoclonal antibodies (mAbs) against growth factors, receptors and tumor
      specific/tumor-selective antigens represent a rapidly growing class of
      pharmaceutical agents which are poised to make a major impact on the treatment of
      colorectal cancer. mAbs targeting the epidermal growth factor receptor and the
      vascular endothelial growth factor have already been approved for the treatment
      of metastatic colorectal cancer. Other antibodies to the same and other molecular
      targets implicated in tumor growth and metastasis are undergoing intense
      preclinical and clinical evaluation. In both the neoadjuvant and adjuvant
      clinical settings, although mAbs are typically administered in combination with
      established cytotoxic chemotherapy regimens given their synergistic effect,
      several agents have demonstrated efficacy when given as monotherapy. At the same
      time, combination therapies with multiple targeted biological agents are actively
      being investigated. Existing clinical data and recent progress in preclinical and
      clinical studies of mAbs are reviewed.

PMID- 17555374
TI  - T-cell receptor gene transfer by lentiviral vectors in adoptive cell therapy.
AB  - Adoptive cell therapy can be envisioned as a promising strategy for tumour
      immunotherapy. However, existing protocols of adoptive cell therapy still require
      optimisation as many factors, such as specificity, avidity, level of
      differentiation and amount of transferred T lymphocytes, can influence their
      immunocompetence and in vivo functionality. In particular, the need to reduce the
      in vitro expansion phase and to obtain large numbers of tumour-reactive T cells,
      as a favourable condition for cancer regression, make TCR gene transfer a
      potentially ideal tool to overcome the limits of adoptive cell therapy
      strategies. Here, the authors review the state-of-the-art and recent advances in
      TCR transfer with particular emphasis on lentiviral vector systems. Initial data
      from preclinical models and recent clinical trials encourage optimisation of a
      safe, simplified and stable transfer system. In this regard, HIV-based vectors
      are emerging as good alternative candidates over the most widely used
      oncoretroviral vectors due to their peculiar molecular features that fit the
      ideal conditions for donor T cell in vitro manipulation.

PMID- 17555373
TI  - The molecular basis of antibody-mediated neutralization of West Nile virus.
AB  - The study of the interaction between the West Nile virus envelope protein and
      monoclonal antibodies has provided insight into the molecular mechanisms of
      neutralization. Structural studies have identified an epitope on the lateral
      ridge of domain III of the West Nile virus E protein that is recognized by
      antibodies with the strongest neutralizing activity in vitro and in vivo.
      Antibodies that bind to this epitope are particularly inhibitory because they
      block infection at a post-attachment step and at concentrations that result in a
      low occupancy of the available sites on the virion.

PMID- 17555375
TI  - Early events in innate immunity in the recognition of microbial pathogens.
AB  - Innate immunity is characterised by a rapid action of host effector molecules and
      leukocytes aimed at limiting the multiplication of invading microbial organisms
      and destroying them. The recognition and destruction of microorganisms involves
      humoral factors (e.g., the complement system and natural antibodies) and
      different cell types (e.g., phagocytic cells, mast cells, natural killer cells).
      Microbial detection by cells involves germ line-encoded pattern-recognition
      receptors such as Toll-like receptors and nucleotide-binding oligomerization
      domain-like receptors. Cellular activation by pathogens leads to the release of
      antimicrobial peptides (e.g., defensins and peptidoglycan recognition proteins)
      and cytokines that orchestrate the anti-infectious response. Cytokines enhance
      phagocytosis and leukocyte microbicidal activity, allow cellular recruitment into
      the infectious focus, boost hematopoiesis, induce fever and lead to the
      production of acute phase proteins.

PMID- 17555376
TI  - The PAPM, diffusion theory, and violent death surveillance.
AB  - OBJECTIVE: To Apply the PAPM and Diffusion Theory for building a statewide
      coroner investigation system to further violent death prevention efforts.
      METHODS: By utilizing a theoretically based framework and systematically tracking
      stage progression, individual agencies and/or state systems can replicate and
      sustain the process. RESULTS: Through the incorporation of the combined models,
      82 of Kentucky's 120 coroner offices currently collect the same information-no
      replicate information existed 4 years ago. CONCLUSION: This study demonstrates
      the utility of theory as a foundation for encouraging adoption of innovation and
      shows an effective way to coordinate information in a timely manner with limited
      cost.

PMID- 17555377
TI  - Smokers' preferences for medicinal nicotine vs smokeless tobacco.
AB  - OBJECTIVE: To assess and compare smokers' interest in medicinal nicotine (MN) and
      smokeless tobacco (SLT) and preference between them. METHODS: Two studies
      presented US smokers verbally with MN and SLT concepts and assessed their appeal
      as smoking substitutes. Both studies evaluated interest and preference between
      products, with attention to the hypothesis that SLT is preferred over MN.
      RESULTS: Study 1 described well-known MN and SLT products. Fifty-nine percent
      preferred MN and 22% SLT. Study 2 presented less familiar MN and SLT products.
      Forty-four percent preferred MN and 35% SLT. CONCLUSIONS: The data show that MN
      products, as presented to smokers in this study, are perceived to be more
      appealing to smokers.

PMID- 17555379
TI  - Factors associated with physical inactivity among korean men and women.
AB  - OBJECTIVES: To identify the independently associating factors on physical
      inactivity in Korean men and women. METHODS: The data of 5554 men and women (18
      74 years) were analyzed using national health and nutritional examination survey
      data that included questionnaires and physical examinations. RESULTS: Multiple
      logistic regression analyses showed that significant factors were low monthly
      income, low education, current smoking, increased waist-to-hip ratio, and low
      health concern among men; living in rural areas, low monthly income, low
      education, perceived poor health status, low health concern, and emotional stress
      among women. CONCLUSIONS: Health care providers should focus on education and
      counseling regarding the factors that influence physical inactivity.

PMID- 17555378
TI  - Caffeine's influence on nicotine's effects in nonsmokers.
AB  - OBJECTIVE: To determine if nicotine's effects are influenced by caffeine in
      nonsmoking, moderate-caffeine consuming individuals (N=20). METHODS: The first 3
      sessions included one of 3 randomly ordered, double-blind caffeine doses (0, 75,
      or 150 mg, oral [po]) and 2 single-blind nicotine gum doses (2 and 4 mg) in
      ascending order. The fourth session (single blind) repeated the 0 mg caffeine
      condition. RESULTS: Nicotine increased heart rate and subjective ratings
      indicative of aversive effects, and decreased reaction times. These effects were
      independent of caffeine dose and reliable across sessions. CONCLUSIONS: In
      nonsmokers, nicotine effects are not influenced by moderate caffeine doses.

PMID- 17555380
TI  - Spirituality and social support on health behaviors of african american
      undergraduates.
AB  - OBJECTIVES: To examine the role of spirituality and perceived social support as
      protective factors for preventing health-compromising behaviors among African
      American college students. METHODS: Two hundred eleven African American college
      students completed a spirituality, perceived social support, and health behavior
      questionnaire. RESULTS: Low spiritual well-being significantly increased the odds
      of smoking and alcohol use. Low perceived parental support increased the odds of
      alcohol use whereas low perceived support from friends decreased the odds of
      alcohol use. CONCLUSIONS: Spirituality and perceived social support may serve as
      protective factors for smoking and alcohol use among African American college
      students.

PMID- 17555382
TI  - Comparison of health behaviors among single- and multiple-member households.
AB  - OBJECTIVE: To assess the differences in health behavior between multiple-member
      and single-member households by gender. METHODS: Face-to-face household survey
      interviews were conducted. The relationship between health behaviors and living
      arrangement was assessed by adjusting for SES. RESULTS: Women living alone
      exercised more and ate less food high in fat. More highly educated men were less
      likely to exercise 5 or more times a week than high school or less educated men.
      CONCLUSIONS: By analyzing local data, a profile can be established to develop and
      implement appropriate public health programs aimed at these various target
      communities for effective intervention and healthy change in the community.

PMID- 17555383
TI  - What do adult smokers think about ads and promotional materials for PREPs?
AB  - OBJECTIVE: To describe adult smokers' reactions to PREP print advertisements and
      promotional materials. METHODS: Focus groups with adult smokers. Participants
      reacted to print advertisements and promotional materials for Omni, Accord,
      Advance Lights, Ariva, and Eclipse. RESULTS: Images and text in PREP product
      advertising and promotional materials influence participants' decision to try
      PREPs. Participants believed the PREP ads target smokers who are trying to quit
      or smokers who are health conscious. CONCLUSION: Tracking and monitoring the
      reactions of smokers to novel products, their perceptions about them, and their
      use of these products are necessary for the design of effective health
      communication strategies.

PMID- 17555381
TI  - Colorectal cancer screening in 3 racial groups.
AB  - OBJECTIVES: To understand predictors of colorectal cancer (CRC) screening in
      African Americans, European Americans, and Native Americans as these groups
      differ in CRC incidence and mortality. METHODS: Participants were surveyed for
      knowledge, beliefs, and behaviors related to CRC. RESULTS: Predictive regression
      modeling found, after adjusting for race, CRC risk, and CRC worry, the odds of
      screening within guidelines were increased for men, those receiving doctor's
      recommendation, those with polyp/tumor history, those under 70, those with more
      knowledge about CRC, and those with fewer barriers to screening. CRC screening
      rates did not differ by race. CONCLUSIONS: These results reiterate the importance
      of knowledge, barriers, and physician recommendation for CRC screening in all
      racial groups.

PMID- 17555384
TI  - Do Latino immigrants link self-rated health with BMI and health behaviors?
AB  - OBJECTIVES: To assess the association between self-rated health, obesity, and
      self-reported health behaviors of Latino immigrants METHODS: Two hundred two
      Latino immigrants (mean age=31.63, SD=8.30, 54% female) participated in a 15
      minute interview and height and weight measurements. RESULTS: Participants
      reporting good to excellent health reported engaging in physical activity during
      the past month (P<.05), eating more fruits and vegetables (P<.001 and P<.01
      respectively), and watching less television (P<.01) than did those who reported
      fair to poor health. Self-rated health was not associated with BMI. CONCLUSIONS:
      Greater attention to Latinos' self-perception of health in relation to weight is
      needed to develop interventions to improve health status.

PMID- 17555386
TI  - Lymph node density: surrogate marker for quality of resection in bladder cancer?

PMID- 17555385
TI  - Effects of individual components of multiple behavior changes: the PREMIER trial.
AB  - OBJECTIVES: To assess contributions of individual lifestyle changes on systolic
      blood pressure (SBP) changes. METHODS: We examined associations between lifestyle
      behavior changes and SBP after 6 and 18 months in 782 PREMIER trial participants.
      RESULTS: In multivariate models omitting weight, predicted SBP reductions ranged
      from (1)/2 to 1(1)/2 mm Hg for reduced urinary sodium, improved fitness, and
      adherence to the DASH diet (except sodium at 18 months). With weight included,
      only fitness change additionally predicted SBP at 18 months. CONCLUSIONS: Several
      lifestyle behavior changes are important for BP lowering, but are difficult to
      detect when weight is included in multivariate models.

PMID- 17555388
TI  - Motexafin gadolinium: a novel radiosensitizer for brain tumors.
AB  - Despite advances in the field of oncology, progress for patients with brain
      metastases and most primary brain tumors has been slow. New efforts to enhance
      the therapeutic index of radiation therapy are under way, including the use of
      radiosensitizers. Motexafin gadolinium (Xcytrin) is one such novel agent with
      several unique properties that enhance the cytotoxic potential of radiation
      therapy, as well as several chemotherapeutic agents, and possibly has independent
      cytotoxicity in certain lymphoid malignancies. Motexafin gadolinium is very well
      tolerated with tumor specific uptake. The rationale for the use of this drug as
      well as its current and future role as a radiation enhancer in the management of
      brain tumors is reviewed.

PMID- 17555389
TI  - Topotecan for the treatment of small-cell lung cancer.
AB  - Lung cancer is the most prevalent and yet the most preventable malignancy
      worldwide. Owing to the propensity of small-cell lung cancer to early relapse and
      its relative resistance to subsequent treatment there is a need to improve
      currently available therapies. Topotecan has provided an efficacious and
      tolerable therapeutic option for patients with recurrent small-cell lung cancer,
      and the oral formulation has also been shown to be beneficial, even in elderly
      patients of poor performance status. Herein we review the role of topotecan in
      the treatment of small-cell lung cancer.

PMID- 17555390
TI  - Capecitabine in the treatment of colorectal cancer.
AB  - Capecitabine is an oral prodrug of 5-fluorouracil. It is being increasingly used
      in the treatment of colorectal cancer in both the adjuvant and metastatic
      settings. This review aims to explore the data in relation to the pharmacology
      and mode of action of capecitabine, followed by an in-depth review of the
      available clinical evidence for the use of capecitabine as a single agent, or in
      combination therapy, in the treatment of colorectal cancer. The pharmacoeconomic
      and medical resource use implications are also investigated. The future role of
      capecitabine in the treatment of colorectal cancer and the questions that remain
      to be answered with regard to its optimal use are considered.

PMID- 17555391
TI  - Effect of cancer and cancer treatment on human reproduction.
AB  - Cancer affecting children and individuals of reproductive age is associated with
      dilemmas concerning the ability to have a child and whether this child will be
      healthy. This is particularly true in light of the recent advances in the early
      detection of cancer and its effective treatment, which has improved survival
      rates. Both the cancer itself and its treatment have tremendous adverse effects
      on human reproduction and may result in the complete termination of reproductive
      ability both in men and women. Even in situations when conception is successfully
      achieved following cancer diagnosis and treatment, there are concerns regarding
      the potential increased risk of adverse obstetric and perinatal outcomes. This is
      especially true when pregnancy occurs shortly after cancer treatment. Moreover,
      there is a potential risk of chromosomal abnormalities and malformations in the
      offspring due to possible genetic defects in the germ cells induced by
      chemotherapy and radiotherapy. In addition, there is (at least theoretically) an
      increased risk of cancer developing in the offspring, particularly with
      hereditary cancer syndromes. A multidisciplinary team aware of the possible
      consequences of cancer treatment on reproduction is very much needed to provide
      optimal care for these patients after proper counseling regarding the potential
      adverse effects of cancer treatment on reproduction.

PMID- 17555392
TI  - High-intensity focused ultrasound ablation of breast cancer.
AB  - The noninvasive ablation of tumors with high-intensity focused ultrasound (HIFU)
      energy has received increasingly widespread interest. The temperature within the
      focal volume of an ultrasound beam is rapidly raised to cytotoxic levels. HIFU
      can selectively ablate a targeted tumor at depth without any damage to
      surrounding or overlying tissues. Animal studies have shown that HIFU ablation is
      safe and effective for the treatment of implanted breast malignancies. The
      results from early clinical trials (Phase I and II) are encouraging, suggesting
      that HIFU is a promising treatment for small breast cancer. Once oncologic
      efficacy data from large-scale randomized clinical trials are available, HIFU
      ablation may become an attractive treatment option for patients with small breast
      cancer, especially the elderly.

PMID- 17555393
TI  - Nanotechnology for targeted cancer therapy.
AB  - Cancer nanotechnology is currently under intense development for applications in
      cancer imaging, molecular diagnosis and targeted therapy. The basic rationale is
      that nanometer-sized particles, such as biodegradable micelles, semiconductor
      quantum dots and iron oxide nanocrystals, have functional or structural
      properties that are not available from either molecular or macroscopic agents.
      When linked with biotargeting ligands, such as monoclonal antibodies, peptides or
      small molecules, these nanoparticles are used to target malignant tumors with
      high affinity and specificity. In the 'mesoscopic' size range of 5-100 nm in
      diameter, nanoparticles also have large surface areas and functional groups for
      conjugating to multiple diagnostic (e.g., optical, radioisotopic or magnetic) and
      therapeutic (e.g., anticancer) agents. Recent advances have led to
      multifunctional nanoparticle probes for molecular and cellular imaging,
      nanoparticle drugs for targeted therapy, and integrated nanodevices for early
      cancer detection and screening. These developments have opened exciting
      opportunities for personalized oncology in which cancer detection, diagnosis and
      therapy are tailored to each individual's molecular profile, and also for
      predictive oncology, in which genetic/molecular information is used to predict
      tumor development, progression and clinical outcome.

PMID- 17555394
TI  - Outcomes and prognosis in advanced renal cell carcinoma.
AB  - Breakthroughs in understanding the pathogenesis of renal cell carcinoma have led
      to recent therapeutic advances in this disease. However, the US FDA approval of
      sunitinib and sorafenib (and soon temsirolimus) after successful Phase III trials
      must also be attributed to the work of clinical investigators over the past
      decade defining the outcomes and major prognostic factors in patients with
      advanced renal cell carcinoma. Those past studies have been critical in providing
      a context for the interpretation of future trials with novel agents, optimizing
      patient selection for specific therapeutic approaches and identifying appropriate
      variables for patient stratification on randomized trials. This review will focus
      on studies that define the outcome and prognosis in advanced renal cell
      carcinoma.

PMID- 17555395
TI  - Patterns of recurrence and surveillance strategies for renal cell carcinoma
      following surgical resection.
AB  - Renal cell carcinoma (RCC) remains one of the most lethal urologic malignancies,
      with up to 40% of patients eventually dying of cancer progression. Despite
      advances in the diagnosis, staging and treatment of patients with RCC,
      approximately a third of patients who undergo surgery for clinically localized
      RCC will suffer a recurrence. Timely identification of recurrences following
      surgical extirpation is imperative in the treatment of these patients. RCC is
      known to metastasize through hematogenous routes of spread to distant organ sites
      and via lymphatic channels to regional lymph nodes. The path of tumor escape is
      associated with diverse clinical outcomes and a unique tumor biology. A consensus
      on surveillance regimens for patients following surgical resection of localized
      disease is lacking. The most extensively used system for providing prognostic
      information regarding survival and recurrence of disease has historically been
      the tumor-node-metastasis (TNM) classification system. As a result, most
      contemporary surveillance protocols have tailored follow-up regimens according to
      stage-based stratifications. Numerous studies have recently demonstrated that
      certain clinical and histopathological factors can improve the prediction of
      tumor recurrence. The incorporation of these prognostic factors into stage-based
      stratification models should be better than stage alone in attempting to provide
      a rational approach to identifying treatable recurrences while minimizing
      unnecessary exams and tests, as well as patient anxiety. Advances in the
      understanding of the pathogenesis, behavior and molecular biology of RCC have
      paved the way for developments that may enhance early diagnosis and
      prognostication, and improve survival for patients. Lastly, molecular markers
      should, in the future, revolutionize surveillance protocols for RCC by tailoring
      follow-up to specific molecular classifications.

PMID- 17555396
TI  - Targeting the PI3K-Akt pathway in kidney cancer.
AB  - Kidney cancer, or renal cell carcinoma, is a relatively rare malignancy but is
      metastatic at diagnosis in a third of patients; metastatic disease has a dismal
      prognosis. Conventional chemotherapy has been woefully inadequate, thus novel
      targets for 'designer' therapies are being actively evaluated. The PI3K-Akt
      signaling cascade, owing to its dual role in both survival and mitogenic
      signaling, is in theory an ideal therapeutic target for this disease, but may
      also represent its fatal flaw. Thus, largely due to toxicity issues, no PI3K or
      Akt inhibitors are currently ready for clinical application. In this review, we
      discuss PI3K-Akt inhibitors as well as inhibitors of pathways and targets both
      immediately up- and downstream of this cascade, many of which show promise in the
      clinic.

PMID- 17555397
TI  - Second-line therapy for esophageal cancer.
AB  - Esophageal cancer is a highly lethal disease, with most patients presenting with
      unresectable or metastatic disease. Since metastatic esophageal cancer is an
      incurable disease, the goals for chemotherapy are to palliate symptoms and
      improve survival. Although some patients may achieve symptomatic improvement with
      the use of standard first-line chemotherapy regimens, response rates are usually
      low and short lasting. Virtually all patients with metastatic esophageal cancer
      will develop progressive disease following front-line therapy. With the
      availability of several chemotherapeutic agents with more tolerable side effects,
      a number of patients who retain a good performance status after the initial
      treatment remain candidates for additional therapy. This review summarizes the
      recent advances in second-line therapy for esophageal cancer.

PMID- 17555398
TI  - Medullary thyroid carcinoma: surgical treatment advances.
AB  - Since medullary thyroid cancer (MTC) was first recognized as a distinct tumor in
      1959, it became clear that MTC is more difficult to cure than papillary thyroid
      cancer and has higher rates of recurrence and mortality. MTC represents 5-8% of
      thyroid cancers. It derives from parafollicular cells of the ultimobranchial body
      derived from the neural crest. MTC secretes calcitonin and other hormonal
      peptides and is considered part of the amine precursor uptake and decarboxilation
      system. MTC may occur either as a hereditary or nonhereditary entity. Hereditary
      MTC can occur either alone as the familial MTC or as the thyroid manifestation of
      multiple endocrine neoplasia (MEN) type 2 syndromes (MEN 2A MEN 2B). Activating
      point mutations of the RET proto-oncogene have demonstrated to be causative of
      the familial form of medullary thyroid cancer, both isolated familial MTC and
      associated with MEN 2A and 2B. In the last 10 years, major improvements and new
      technologies have been proposed and applied in thyroid surgery; among these are
      molecular diagnosis with genetic screening and mini-invasive video-assisted
      thyroidectomy. The history of thyroid surgery starts with Billroth, Kocher and
      Halsted, who developed the technique for thyroidectomy between 1873 and 1910.
      Prophylactic surgery for patients carrying a positive RET proto-oncogene has
      proven to be highly effective in curing those likely to experience the
      development of MTC. Video-assisted procedures with central compartment dissection
      have proved feasible for patients carrying a positive RET proto-oncogene. This
      paper reviews relevant medical literature published in the English language on
      surgery of MTC in well-controlled trials. We discuss the particular ethical and
      legal issues that thyroid prophylactic surgery raises. Searches were last updated
      in February 2007.

PMID- 17555399
TI  - Neoadjuvant chemotherapy for patients with liver metastases from colorectal
      cancer.
AB  - Colorectal cancer is the second most common type of cancer in industrialized
      countries. Despite improved resection procedures and optimized adjuvant
      chemotherapy, local or distant recurrences occur in 22-25% of patients with stage
      II/III colon cancer. Approximately 30% of patients have advanced disease at
      presentation. The liver is the most common site of colorectal metastases and,
      interestingly, 20-30% of patients with colorectal cancer have liver-only
      metastases. The combined modality of chemotherapy and surgery increases overall
      survival and the chance of cure for metastatic patients, even if there is no
      agreement in terms of the best schedule and how long the treatment must last. In
      this paper, we review the role and the rationale of neoadjuvant chemotherapy
      within a multimodal approach, and discuss remaining questions and future
      directions.

PMID- 17555400
TI  - Cytochrome c oxidase rather than cytochrome c is a major determinant of
      mitochondrial respiratory capacity in skeletal muscle of aged rats: role of
      carnitine and lipoic acid.
AB  - The release of mitochondrial cytochrome c followed by activation of caspase
      cascade has been reported with aging in various tissues, whereas little is known
      about the caspase-independent pathway involved in mitochondrial dysfunction. To
      determine the functional impact of cytochrome c loss on mitochondrial respiratory
      capacity, we monitored NADH redox transitions and oxygen consumption in isolated
      skeletal muscle mitochondria of 4- and 24-month-old rats in the presence and
      absence of exogenous cytochrome c; and assessed the efficacy of cosupplementation
      of carnitine and lipoic acid on age-related alteration in mitochondrial
      respiration. The loss of mitochondrial cytochrome c with age was accompanied with
      alteration in respiratory transition, which in turn was not rescued by exogenous
      addition of cytochrome c to isolated mitochondria. The analysis of mitochondrial
      and nuclear-encoded cytochrome c oxidase subunits suggests that the decreased
      levels of cytochrome c oxidase may be attributed for the irresponsiveness to
      exogenously added cytochrome c on mitochondrial respiratory transitions, possibly
      through reduction of upstream electron carriers. Oral supplementation of
      carnitine and lipoic acid to aged rats help to maintaining the mitochondrial
      oxidative capacity by regulating the release of cytochrome c and improves
      cytochrome c oxidase transcript levels. Thus, carnitine and lipoic acid
      supplementation prevents the loss of cytochrome c and their associated decline in
      cytochrome c oxidase activity; thereby, effectively attenuating any putative
      decrease in cellular energy and redox status with age.

PMID- 17555401
TI  - Caspase-9 cleavage, do you need it?
AB  - Caspase-9, which is activated by association with the Apaf-1 (apoptotic protease
      activating factor-1) apoptosome complex, cleaves and activates the downstream
      effector caspases-3 and -7, thereby executing the caspase-cascade and cell-death
      programme. Although caspase-9 does not need to be cleaved to be active, apoptotic
      cell death is always accompanied by autocatalytic cleavage and by further
      downstream effector caspase-dependent cleavage of caspase-9. In this issue of the
      Biochemical Journal, Denault and co-workers evaluate the role of caspase-3
      dependent cleavage of caspase-9 and conclude that this mechanism mainly serves to
      enhance apoptosis by alleviating XIAP (X-linked inhibitor of apoptosis)
      inhibition of the apical caspase.

PMID- 17555402
TI  - Oxygen-dependent regulation of mitochondrial respiration by hypoxia-inducible
      factor 1.
AB  - The survival of metazoan organisms is dependent upon the utilization of O2 as a
      substrate for COX (cytochrome c oxidase), which constitutes Complex IV of the
      mitochondrial respiratory chain. Premature transfer of electrons, either at
      Complex I or at Complex III, results in the increased generation of ROS (reactive
      oxygen species). Recent studies have identified two critical adaptations that may
      function to prevent excessive ROS production in hypoxic cells. First, expression
      of PDK1 [PDH (pyruvate dehydrogenase) kinase 1] is induced. PDK1 phosphorylates
      and inactivates PDH, the mitochondrial enzyme that converts pyruvate into acetyl
      CoA. In combination with the hypoxia-induced expression of LDHA (lactate
      dehydrogenase A), which converts pyruvate into lactate, PDK1 reduces the delivery
      of acetyl-CoA to the tricarboxylic acid cycle, thus reducing the levels of NADH
      and FADH2 delivered to the electron-transport chain. Secondly, the subunit
      composition of COX is altered in hypoxic cells by increased expression of the
      COX4-2 subunit, which optimizes COX activity under hypoxic conditions, and
      increased degradation of the COX4-1 subunit, which optimizes COX activity under
      aerobic conditions. Hypoxia-inducible factor 1 controls the metabolic adaptation
      of mammalian cells to hypoxia by activating transcription of the genes encoding
      PDK1, LDHA, COX4-2 and LON, a mitochondrial protease that is required for the
      degradation of COX4-1. COX subunit switching occurs in yeast, but by a completely
      different regulatory mechanism, suggesting that selection for O2-dependent
      homoeostatic regulation of mitochondrial respiration is ancient and likely to be
      shared by all eukaryotic organisms.

PMID- 17555404
TI  - Mechanisms for the role of tetrahydrobiopterin in endothelial function and
      vascular disease.
AB  - NO produced by eNOS (endothelial nitric oxide synthase) is a key mediator of
      vascular homoeostasis. NO bioavailability is reduced early in vascular disease
      states, such as hypercholesterolaemia, diabetes and hypertension, and throughout
      the progression of atherosclerosis. This is a result of both reduced NO synthesis
      and increased NO consumption by reactive oxygen species. eNOS enzymatic activity
      appears to be determined by the availability of its cofactor BH4
      (tetrahydrobiopterin). When BH4 levels are adequate, eNOS produces NO; when BH4
      levels are limiting, eNOS becomes enzymatically uncoupled and generates
      superoxide, contributing to vascular oxidative stress and endothelial
      dysfunction. BH4 bioavailability is determined by a balance of enzymatic de novo
      synthesis and recycling, versus oxidative degradation in dysfunctional
      endothelium. Augmenting vascular BH4 levels by pharmacological supplementation,
      by enhancing the rate of de novo biosynthesis or by measures to reduce BH4
      oxidation have been shown in experimental studies to enhance NO bioavailability.
      Thus BH4 represents a potential therapeutic target for preserving eNOS function
      in vascular disease.

PMID- 17555403
TI  - Expression and glycogenic effect of glycogen-targeting protein phosphatase 1
      regulatory subunit GL in cultured human muscle.
AB  - Glycogen-targeting PP1 (protein phosphatase 1) subunit G(L) (coded for by the
      PPP1R3B gene) is expressed in human, but not rodent, skeletal muscle. Its effects
      on muscle glycogen metabolism are unknown. We show that G(L) mRNA levels in
      primary cultured human myotubes are similar to those in freshly excised muscle,
      unlike subunits G(M) (gene PPP1R3A) or PTG (protein targeting to glycogen; gene
      PPP1R3C), which decrease strikingly. In cultured myotubes, expression of the
      genes coding for G(L), G(M) and PTG is not regulated by glucose or insulin.
      Overexpression of G(L) activates myotube GS (glycogen synthase), glycogenesis in
      glucose-replete and -depleted cells and glycogen accumulation. Compared with
      overexpressed G(M), G(L) has a more potent activating effect on glycogenesis,
      while marked enhancement of their combined action is only observed in glucose
      replete cells. G(L) does not affect GP (glycogen phosphorylase) activity, while
      co-overexpression with muscle GP impairs G(L) activation of GS in glucose-replete
      cells. G(L) enhances long-term glycogenesis additively to glucose depletion and
      insulin, although G(L) does not change the phosphorylation of GSK3 (GS kinase 3)
      on Ser9 or its upstream regulator kinase Akt/protein kinase B on Ser473, nor its
      response to insulin. In conclusion, in cultured human myotubes, the G(L) gene is
      expressed as in muscle tissue and is unresponsive to glucose or insulin, as are
      G(M) and PTG genes. G(L) activates GS regardless of glucose, does not regulate GP
      and stimulates glycogenesis in combination with insulin and glucose depletion.

PMID- 17555405
TI  - Mechanisms by which fatty acids regulate leucocyte function.
AB  - Fatty acids (FAs) have been shown to alter leucocyte function and thus to
      modulate inflammatory and immune responses. In this review, the effects of FAs on
      several aspects of lymphocyte, neutrophil and macrophage function are discussed.
      The mechanisms by which FAs modulate the production of lipid mediators, activity
      of intracellular signalling pathways, activity of lipid-raft-associated proteins,
      binding to TLRs (Toll-like receptors), control of gene expression, activation of
      transcription factors, induction of cell death and production of reactive oxygen
      and nitrogen species are described in this review. The rationale for the use of
      specific FAs to treat patients with impaired immune function is explained.
      Substantial improvement in the therapeutic usage of FAs or FA derivatives may be
      possible based on an improvement in the understanding of the precise molecular
      mechanisms of action with respect to the different leucocyte types and outcome
      with respect to the inflammatory responses.

PMID- 17555406
TI  - p53 regulates its own activator: transcriptional co-activator PC4, a new p53
      responsive gene.
AB  - The tumour suppressor protein p53 regulates the expression of several genes that
      mediate cell cycle arrest, apoptosis, DNA repair and other cellular responses.
      Recently, we have shown that human transcriptional co-activator PC4 is a unique
      activator of p53 function. In the present study, we report that PC4 is a p53
      inducible gene. Bioinformatics analysis reveals multiple p53-binding sites in the
      PC4 promoter. We have found that indeed p53 binds to all the identified sites in
      vitro and in vivo with varying affinities. p53 acts as an activator of PC4
      transcription. Both PC4 mRNA and protein levels increase in response to stimuli
      that result in p53 induction. Furthermore, PC4 enhances p53 recruitment to the
      PC4 promoter. Our results thus establish the first report of a positively
      regulated feedback loop to control p53 function.

PMID- 17555407
TI  - Mutant alpha-galactosidase A enzymes identified in Fabry disease patients with
      residual enzyme activity: biochemical characterization and restoration of normal
      intracellular processing by 1-deoxygalactonojirimycin.
AB  - Fabry disease is a lysosomal storage disorder caused by the deficiency of alpha
      Gal A (alpha-galactosidase A) activity. In order to understand the molecular
      mechanism underlying alpha-Gal A deficiency in Fabry disease patients with
      residual enzyme activity, enzymes with different missense mutations were purified
      from transfected COS-7 cells and the biochemical properties were characterized.
      The mutant enzymes detected in variant patients (A20P, E66Q, M72V, I91T, R112H,
      F113L, N215S, Q279E, M296I, M296V and R301Q), and those found mostly in mild
      classic patients (A97V, A156V, L166V and R356W) appeared to have normal K(m) and
      V(max) values. The degradation of all mutants (except E59K) was partially
      inhibited by treatment with kifunensine, a selective inhibitor of ER (endoplasmic
      reticulum) alpha-mannosidase I. Metabolic labelling and subcellular fractionation
      studies in COS-7 cells expressing the L166V and R301Q alpha-Gal A mutants
      indicated that the mutant protein was retained in the ER and degraded without
      processing. Addition of DGJ (1-deoxygalactonojirimycin) to the culture medium of
      COS-7 cells transfected with a large set of missense mutant alpha-Gal A cDNAs
      effectively increased both enzyme activity and protein yield. DGJ was capable of
      normalizing intracellular processing of mutant alpha-Gal A found in both classic
      (L166V) and variant (R301Q) Fabry disease patients. In addition, the residual
      enzyme activity in fibroblasts or lymphoblasts from both classic and variant
      hemizygous Fabry disease patients carrying a variety of missense mutations could
      be substantially increased by cultivation of the cells with DGJ. These results
      indicate that a large proportion of mutant enzymes in patients with residual
      enzyme activity are kinetically active. Excessive degradation in the ER could be
      responsible for the deficiency of enzyme activity in vivo, and the DGJ approach
      may be broadly applicable to Fabry disease patients with missense mutations.

PMID- 17555408
TI  - Inhibition of calcium-independent phospholipase A2 suppresses proliferation and
      tumorigenicity of ovarian carcinoma cells.
AB  - PLA2 (phospholipase A2) enzymes play critical roles in membrane phospholipid
      homoeostasis and in generation of lysophospholipid growth factors. In the present
      study, we show that the activity of the cytosolic iPLA2 (calcium-independent
      PLA2), but not that of the calcium-dependent cPLA2 (cytosolic PLA2), is required
      for growth-factor-independent, autonomous replication of ovarian carcinoma cells.
      Blocking iPLA2 activity with the pharmacological inhibitor BEL (bromoenol
      lactone) induces cell cycle arrest in S- and G2/M-phases independently of the
      status of the p53 tumour suppressor. Inhibition of iPLA2 activity also leads to
      modest increases in apoptosis of ovarian cancer cells. The S- and G2/M-phase
      accumulation is accompanied by increased levels of the cell cycle regulators
      cyclins B and E. Interestingly, the S-phase arrest is released by supplementing
      the growth factors LPA (lysophosphatidic acid) or EGF (epidermal growth factor).
      However, inhibition of iPLA2 activity with BEL remains effective in repressing
      growth-factor- or serum-stimulated proliferation of ovarian cancer cells through
      G2/M-phase arrest. Down-regulation of iPLA2b expression with lentivirus-mediated
      RNA interference inhibited cell proliferation in culture and tumorigenicity of
      ovarian cancer cell lines in nude mice. These results indicate an essential role
      for iPLA2 in cell cycle progression and tumorigenesis of ovarian carcinoma cells.

PMID- 17555409
TI  - TLR2 Arg753Gly, TLR4 Asp299Gly and Thr399Ile gene polymorphisms are not
      associated with chronic periodontitis in a Turkish population.
AB  - AIM: Toll-like receptor (TLR) gene polymorphisms could affect the host's ability
      to respond to microbial pathogens. In this case-control study, the association of
      TLR2 and TLR4 gene polymorphisms with chronic periodontitis (CP) was
      investigated. MATERIALS AND METHODS: Genomic DNA was obtained from the peripheral
      blood of 83 patients with CP and 106 periodontally healthy subjects. The TLR2
      Arg753Gly, Arg677Trp and TLR4 Asp299Gly, Thr399Ile gene polymorphisms were
      genotyped by the polymerase chain reaction-restriction fragment length
      polymorphism method. The data were analysed by a chi2 test, logistic regression
      analysis and the Mann-Whitney U test. RESULTS: The 753Gln allele was found in
      6.1% of the CP patients as compared with 6.6% in the control group (p>0.05). The
      frequency of the 299Gly and 399Ile allele was 2.4% and 1.8% in CP patients. For
      the healthy subjects, the frequency was 2.8% for the 299Gly and 2.5% for the
      399Ile allele (p>0.05). None of the CP patients or healthy subjects showed
      homozygosity for the TLR2 and TLR4 alleles. Percentage of sites with bleeding on
      probing and plaque were significantly higher in 299Gly-positive patients compared
      with 299Gly-negative patients (p<0.05). CONCLUSION: These results showed that the
      TLR2 and TLR4 gene polymorphisms studied are not associated with susceptibility
      to CP in Turkish patients.

PMID- 17555410
TI  - Lipid peroxidation levels and total oxidant status in serum, saliva and gingival
      crevicular fluid in patients with chronic periodontitis.
AB  - OBJECTIVES: Increased levels of reactive oxygen species lead to oxidative stress.
      Recent data suggest increased lipid peroxidation (LPO) levels and oxidative
      stress in periodontitis. Malondialdehyde (MDA), a significant LPO product,
      increases in oxidative stress. In this study, MDA levels and total oxidant status
      (TOS) in serum, saliva and gingival crevicular fluid (GCF) were investigated in
      patients with chronic periodontitis (CP). MATERIALS AND METHODS: Thirty-six CP
      patients and 28 periodontally healthy controls were included in the study.
      Following clinical measurements and samplings, MDA and TOS levels were measured
      by high-performance liquid chromatography and a novel automatic colorimetric
      method, respectively. RESULTS: While the saliva and GCF MDA levels, and serum,
      saliva and GCF TOS values were significantly higher in the CP group than the
      control group (p<0.05), no significant difference in serum MDA levels was found
      (p>0.05). Strong positive correlations were observed between periodontal
      parameters and MDA and TOS levels (p<0.05). CONCLUSIONS: The results revealed
      that LPO significantly increased locally in the periodontal pocket/oral
      environment, while TOS displayed both systemic and local increases in
      periodontitis. The findings suggest that increased LPO and TOS may play an
      important role in the pathology of periodontitis, and are closely related to the
      clinical periodontal status.

PMID- 17555411
TI  - Pre-treatment radiographic features for the periodontal prognosis of treated
      impacted canines.
AB  - AIM: The aim of this study is to evaluate the prognostic role of the pre
      treatment radiographic features on the post-treatment periodontal status of intra
      osseous impacted maxillary canines. MATERIAL AND METHODS: A study population of
      168 patients (211 canines) was evaluated at the end of the overall surgical
      orthodontic treatment consisting of a combined surgical (flap) and orthodontic
      (direct traction to the centre of the ridge) approach. The pre-treatment
      variables on the panoramic radiograph were alpha-angle, d-distance and s-sector
      while the post-treatment periodontal variables were pocket depth (PD) and
      keratinized tissue width (KT). Multilevel statistical analysis was used to
      evaluate the role of the pre-treatment radiographic factors on the post-treatment
      periodontal variables at patient, tooth and site levels. RESULTS: No significant
      differences in PD or KT were found at the end of surgical-orthodontic treatment
      with respect to age, gender, site of impaction or pre-treatment radiographic
      position of the impacted canine. The only statistically, but not clinically,
      significant difference (about 0.5 mm) was found for the KT that was greater for
      the palatally impacted canines than for the buccally impacted ones. CONCLUSIONS:
      alpha-angle, d-distance and s-sector measured on the pre-treatment panoramic
      radiographs did not represent prognostic indicators of final periodontal status
      of orthodontically re-positioned canines.

PMID- 17555412
TI  - Microbiological findings after periodontal therapy using curettes, Er:YAG laser,
      sonic, and ultrasonic scalers.
AB  - AIM: To evaluate and compare the microbiological effects of hand instruments,
      Er:YAG-laser, sonic, and ultrasonic scalers in patients with chronic
      periodontitis. Patient perception of each treatment was documented. MATERIAL AND
      METHODS: From 72 patients, bacterial samples were collected from the deepest
      pocket in each quadrant (total: 288 sites). A polymerase chain reaction kit
      estimated the amount of Aggregatibacter (Actinobacillus) actinomycetemcomitans
      (Aa), Porphyromonas gingivalis (Pg), Prevotella intermedia (Pi), Tannerella
      forsythensis (Tf), and Treponema denticola (Td) at baseline as well as 3 and 6
      months after therapy. One quadrant in each patient was randomly assigned to
      curettes (H-group), Er:YAG laser (L-group), sonic device (S-group), or ultrasonic
      device (U-group). RESULTS: Three months post-operatively, the amounts of Pg, Pi,
      Tf, and Td were significantly reduced in all groups. Laser and sonic
      instrumentation failed to reduce Aa. Six months after therapy, significant
      differences were still detected for Pg (L- and U-group), for Pi and Tf (S-group),
      and for Td (L-, S- and U-group). Patients rated ultrasonic treatment as more
      preferable than hand and laser instrumentation. CONCLUSION: The various treatment
      methods resulted in a comparable reduction of the evaluated periodontal
      pathogens, and bacterial increase was only partially different 6 months post
      operatively. Ultrasonic instrumentation caused less discomfort.

PMID- 17555413
TI  - Effect of constant strain rate, composed of varying amplitude and frequency, of
      early loading on peri-implant bone (re)modelling.
AB  - AIM: Examine the effect of varying components of strain rate -- amplitude versus
      frequency -- while maintaining a constant strain rate of early controlled
      mechanical loading on implant stability, peri-implant bone mass and bone-to
      implant contact. MATERIAL AND METHODS: Three groups of guinea-pigs received TiO2 
      blasted implants in both tibiae. One week after installation test implants were
      loaded 5 days/week during 4 weeks. The contra-lateral implants were the unloaded
      controls. Strain rate was kept constant (1600 micro epsilon/s), while amplitude
      and frequency were varied per group. Implant stability was followed by resonance
      frequency analysis. Animals were sacrificed, and ground sections were prepared to
      rate bone-to-implant contact and bone mass. RESULTS: All implants (n=78)
      integrated uneventfully. A significant positive effect (p=0.03) of early loading
      on bone mass was observed in the distal medullar cavity. A significant difference
      in bone mass between test and control implants was evidenced between the groups
      (p=0.03 and 0.04). A significant increase in implant stability and bone-to
      implant contact could not be shown. CONCLUSIONS: Early controlled stimulation of
      peri-implant bone is related to amplitude/frequency and not to strain rate as
      such, considering a constant stimulation time. An increase of bone mass around
      early-loaded implants was shown. This cortical bone model is most sensitive to
      low-frequency/high-amplitude stimulation.

PMID- 17555414
TI  - Surgical treatment of peri-implantitis using a bone substitute with or without a
      resorbable membrane: a prospective cohort study.
AB  - OBJECTIVES: The aim of this prospective cohort study was to compare two
      regenerative surgical treatment modalities for peri-implantitis. MATERIAL AND
      METHODS: Thirty-six patients having a minimum of one osseointegrated implant,
      with a progressive loss of bone amounting to > or =3 threads (1.8 mm) following
      the first year of healing, combined with bleeding and/or pus on probing, were
      involved in this study. The patients were assigned to two different treatment
      strategies. After surgical exposure of the defect, granulomatous tissue was
      removed and the infected implant surface was treated using 3% hydrogen peroxide.
      The bone defects were filled with a bone substitute (Algipore). In 17 patients
      (Group 1), a resorbable membrane (Osseoquest) was placed over the grafted defect
      before suturing. In 19 patients (Group 2), the graft was used alone. RESULTS: One
      year follow-up demonstrated clinical and radiographic improvements. Probing
      depths were reduced by 2.9 mm in Group 1 and by 3.4 mm in Group 2. Defect fill
      amounted to 1.5 and 1.4 mm, respectively. There was no significant difference
      between the groups. CONCLUSION: It is possible to treat peri-implant defects with
      a bone substitute, with or without a resorbable membrane.

PMID- 17555415
TI  - Astra Tech single-tooth implants: an audit of patient satisfaction and soft
      tissue form.
AB  - AIM: To investigate patient centred outcomes, soft tissue morphology, and bone
      levels. MATERIAL AND METHODS: Sixty-six subjects, who had completed treatment for
      a single implant restoration at least l year previously. Appearance was recorded
      photographically and bone levels and interdental contact points measured from
      intra-oral radiographs using a x 7 scale loupe. Subjects completed a satisfaction
      questionnaire. RESULTS: Subjects were highly satisfied with all aspects of the
      restoration including the appearance of the soft tissue (median shape/colour
      score 6 on scale 1-6). Twenty-eight sites in 20 subjects had no contact point
      between implant crown and adjacent tooth. A normal height papilla was judged to
      be present in 19 of these sites. These were excluded from the subsequent
      analysis. In the remaining 46 subjects with contact points the presence (JEMT
      score 3) or deficiency (score 1/2) of the papilla was significantly related to
      the distance to the bone level on the adjacent tooth and implant head.
      Differences were observed between the mesial and distal aspects of the implant
      restoration. CONCLUSIONS: Examining clinicians were more critical of the
      restorations than the patients. The presence of a complete papilla was associated
      with a slightly greater distance from contact point to bone level than previously
      reported.

PMID- 17555416
TI  - Review article: possible beneficial effects of coffee on liver disease and
      function.
AB  - BACKGROUND: Coffee is consumed by 50 percent of Americans every day. After oil,
      coffee is the second most valuable commodity in the world. In recent years a
      number of studies have suggested potential health risks associated with coffee
      consumption; however, the results are controversial. Whilst coffee has been
      reported to increase cardiovascular risk factors, other investigators have
      demonstrated its protective effects on diseases ranging from type 2 diabetes to
      Parkinson's disease. A number of investigators have focused their attention on
      the relationship between the consumption of coffee and liver disease. AIM: To
      examine the published literature to date in an attempt to establish the presence
      of an hepatoprotective effect of coffee. METHODS: Using PubMed, we identified
      published studies and review articles relating to the effect of coffee
      consumption on diseases of the liver. CONCLUSION: A number of studies have
      reported the beneficial effects of coffee on abnormal liver biochemistry,
      cirrhosis and hepatocellular carcinoma. At the present time the mechanism of this
      effect remains unclear as does the ''dose'' required to achieve these benefits.

PMID- 17555417
TI  - Systematic review: the adverse effects of sodium phosphate enema.
AB  - BACKGROUND: Sodium-phosphate enemas are widely used to treat constipation, and
      are rarely associated with side effects. AIM: A systematic review of the
      literature was conducted to identify the most common adverse effects of sodium
      phosphate enemas and associated risk factors. METHODS: A systematic search was
      conducted in Internet (MEDLINE), and the Cochrane Library, from January 1957 to
      March 2007. RESULTS: A total of 761 references were identified initially, and 39
      relevant papers were finally selected. The most common therapeutic indications
      included constipation (63%). Sixty-eight per cent of the patients having adverse
      effects had associated conditions, the most common being gastrointestinal
      motility disorders, cardiological diseases and renal failure. Virtually, all side
      effects were due to water and electrolyte disturbances. Most patients were under
      18 years of age (66%) or older than 65 years (25%). A total of 12 deaths were
      found. CONCLUSION: The main side effects caused by sodium phosphate enemas are
      water and electrolyte disturbances. The main risk factors are extreme age and
      associated comorbidity.

PMID- 17555418
TI  - Meta-analysis: the efficacy of rectal beclomethasone dipropionate vs. 5
      aminosalicylic acid in mild to moderate distal ulcerative colitis.
AB  - BACKGROUND: Beclomethasone dipropionate (BDP) is a second-generation steroid with
      topical effects and minimal systemic activity for patients with ulcerative
      colitis (UC). AIM: To review all available literature to assess the efficacy of
      enema/foam BDP compared with enema/foam 5-aminosalicylic acid (5-ASA) in the
      control of left-sided mild-moderate UC. METHODS: We selected randomized
      controlled trials of enema/foam BDP compared with enema/foam 5-ASA treatment in
      patients with UC. Two reviewers assessed trial quality and extracted data
      independently. RESULTS: Four trials involving 428 UC patients, 209 treated with 5
      ASA (1-4 g o.d.) and 219 with BDP (3 mg o.d.), were included. Intention-to-treat
      analysis showed that 5-ASA induced improvement/remission of UC in 146 (69.9%)
      patients, while BDP in 143 (65.3%). The test for heterogeneity (Cochran Q) was
      not significant and Mantel-Haenszel pooled estimate of odds ratio was 1.23 (95%
      CI = 0.82-1.85). The results did not change when analysis was performed on a per
      protocol basis. CONCLUSION: The randomized controlled trials identified in this
      review showed that rectal BDP has equal effect as 5-ASA to control symptoms in
      UC.

PMID- 17555419
TI  - Environmental risk factors in the development of adenocarcinoma of the oesophagus
      or gastric cardia: a cross-sectional study in a Dutch cohort.
AB  - BACKGROUND: Risk factors for adenocarcinoma of the oesophagus (OAC) and gastric
      cardia (GCA) are not yet established. AIM: To compare environmental risk factors
      between patients with OAC and GCA. METHODS: One-hundred and twenty-six patients
      with OAC, 43 with GCA and 57 with squamous cell carcinoma filled out a
      questionnaire with information on demographic and lifestyle characteristics,
      physical activity levels, family history, gastro-oesophageal reflux disease
      symptoms and medication use. RESULTS: OAC and GCA patients were similar with
      regard to male predominance and age, alcohol intake and smoking, use of fruits
      and vegetables, body posture and occupational activities (P > 0.05). GCA patients
      less often had heartburn compared with OAC patients [odds ratio (OR) 0.5, 95%
      confidence interval (CI) 0.2-0.96] and had these symptoms less frequently and for
      a shorter period (OR 0.3, CI 0.1-1.0 and OR 0.1, CI 0.03-0.6, respectively).
      Former and current aspirin use was lower among GCA patients than OAC patients (OR
      0.2, CI 0.05-0.7 and OR 0.4, CI 0.1-0.9, respectively), whereas no difference in
      non-steroidal anti-inflammatory drug use was detected. CONCLUSION: Although OAC
      and GCA share several environmental risk factors, OAC is more frequently
      associated with a history of gastro-oesophageal reflux disease, suggesting a more
      important role for gastro-oesophageal reflux in OAC compared with GCA.

PMID- 17555420
TI  - Comparisons of the distribution of oesophageal acid exposure throughout the sleep
      period among the different gastro-oesophageal reflux disease groups.
AB  - BACKGROUND: Nocturnal gastro-oesophageal reflux diseases (GERD) can lead to
      oesophageal mucosal injury and extra-oesophageal complications. AIM: To compare
      distribution of oesophageal acid exposure during sleep time among patients with
      non-erosive reflux disease and abnormal pH test (NERD-positive), erosive
      oesophagitis (EO) and Barrett's oesophagus (BO). METHODS: Patients underwent
      endoscopy followed by 24-h oesophageal pH testing. Oesophageal acid exposure was
      assessed every 2 h of the sleep period (0-2, 2-4, 4-6 and 6-8 h). Each period of
      2 h was evaluated for acid reflux parameters. All groups were matched by age,
      time from last meal and duration of sleep time. RESULTS: Thirty-eight patients
      were enrolled (NERD-positive, 16; EO, 1.4; and BO, 8). All GERD groups
      demonstrated higher oesophageal acid exposure in the first vs. second half of the
      sleep period as determined by percent time pH <4 (BO: 34.7 vs.11.6, EO: 13.5 vs.
      6.9, NERD-positive: 8.8 vs. 2.5, all P < 0.01). In general, patients with BO had
      a significantly higher distribution of oesophageal acid exposure than those with
      NERD-positive and EO. CONCLUSIONS: Oesophageal acid exposure generally declines
      throughout the sleep period regardless of GERD group, but BO patients
      demonstrated the greatest decline during the sleep period.

PMID- 17555421
TI  - Enbucrilate for gastric varices: extended experience in 92 patients.
AB  - AIM: We assessed N-2-butyl-cyanoacrylate (enbucrilate) in 92 patients with
      gastric variceal bleeding under an FDA-approved investigation. These results
      extend our prior report of the first 44 patients. METHOD: Injection was performed
      with enbucrilate and ethiodol (1:1). Eighty patients had portal hypertension and
      12 had splenic vein thrombosis. RESULTS: In the portal hypertensive group, re
      bleeding from gastric varices was seen in 4 of 80 (5%) from 0 to 72 h, 5 of 76
      (6.5%) from > 72 h to 3 months and 9 of 51 (17%) from > 3 months to 1 year. Re
      bleeding and survival were significantly related to the Child-Pugh class. In the
      splenic vein thrombosis group (n = 12), there was early rebleeding in 2 (17%)
      patients from 0 to 72 h, 1 (8%) from > 72 h to 3 months and none in the chronic
      phase (> 3 months to 1 year) although 1-year survival in this group was only 6
      (50%) due to the underlying malignancy in most. Serious embolization was
      suspected in 2 patients (2%). CONCLUSION: Enbucrilate offers an important
      intervention in gastric variceal bleeding which should be further studied in the
      US. A randomized trial is warranted to compare this intervention to radiological
      therapy.

PMID- 17555422
TI  - Role of intra-oesophageal impedance monitoring in the evaluation of endoscopic
      gastroplication for gastro-oesophageal reflux disease.
AB  - BACKGROUND: In the evaluation of several endoscopic antireflux procedures, a
      discrepancy in the degree of improvement between symptoms and objective reflux
      parameters as measured by pH-metry has been reported. AIM: To assess the
      additional value of impedance monitoring in the evaluation of endoscopic
      gastroplication for gastro-oesophageal reflux disease. METHODS: Eighteen patients
      with gastro-oesophageal reflux disease were treated with three endoscopic
      gastroplications, and underwent 24 h pH-impedance monitoring before and 3 months
      after treatment. RESULTS: Total reflux exposure time as assessed by pH-metry and
      impedance monitoring was significantly decreased after treatment (P = 0.047 and
      <0.001, respectively). When assessed with impedance monitoring, the mean number
      of reflux episodes was significantly decreased after the procedure (82 vs. 56,
      pre vs. post, P < 0.001). Furthermore, the mean numbers of liquid and acid reflux
      episodes in patients with symptomatic improvement were significantly reduced
      after treatment (P = 0.04 and 0.02, respectively). After treatment, mean volume
      clearance time (s) and mean number of proximal reflux episodes were significantly
      decreased (P < 0.001 and 0.002, respectively). CONCLUSIONS: Impedance monitoring
      can identify the specific effect of endoscopic gastroplication on the different
      types of reflux episodes with regard to gas-liquid composition and pH, as well as
      on volume clearance and the proximal extent of the refluxate.

PMID- 17555423
TI  - Efficacy of rabeprazole on heartburn symptom resolution in patients with non
      erosive and erosive gastro-oesophageal reflux disease: a multicenter study from
      Japan.
AB  - BACKGROUND: Few studies have compared the efficacy of proton pump inhibitors in
      resolving the symptoms of non-erosive reflux disease (NERD) and of erosive gastro
      oesophageal reflux disease (GERD) in Japan. AIM: To investigate and compare the
      efficacy of 4-week course of rabeprazole 10 mg/day on symptom resolution in NERD
      and erosive GERD in Japan. METHODS: The modified Los Angeles classification was
      used to grade endoscopically GERD in patients with heartburn (Grades N and M:
      NERD, Grades A and B: mild reflux oesophagitis (RO), and Grades C and D: severe
      RO). Rabeprazole 10 mg/day was administered for 4 weeks to 180 patients who kept
      symptom diaries. RESULTS: Complete relief of the symptoms was achieved in 35.8%
      of the NERD group and 55.4% of the erosive GERD group (mild RO: 51.1% and severe
      RO: 77.8%). Rabeprazole was significantly more effective in erosive GERD than in
      NERD patients. Among the NERD subgroups (Grades N and M), no difference in
      symptom improvement was observed. CONCLUSIONS: Four-week, rabeprazole 10 mg/day
      acid suppression therapy was effective in resolving symptoms in Japanese GERD
      patients. This therapy was more effective in erosive GERD than in NERD patients,
      and in those with severe RO than in those with mild RO.

PMID- 17555424
TI  - Long-term follow-up of patients with mild to moderate drug-induced liver injury.
AB  - AIM: To evaluate the long-term prognosis of patients diagnosed with drug-induced
      liver injury, and the nature of the liver injury. METHODS: Patients with a
      diagnosis of drug-induced liver injury between 1994 and 2005 were identified in a
      university hospital clinic. Patients surviving drug-induced liver injury
      associated liver failure were excluded. RESULTS: Seventy-seven cases were
      identified and those who were alive (69) were invited to attend follow-up. Of
      those patients who had died, none had died of liver disease. Of those patients
      who had survived, 59 were reviewed in the clinic. Patients had a median follow-up
      of 48 months. Before the diagnosis of drug-induced liver injury, nine had a
      chronic liver disease, four with autoimmune hepatitis, two with non-alcoholic
      liver disease, one each with non-alcoholic fatty liver disease, primary biliary
      cirrhosis and primary sclerosing cholangitis. There was no evidence of
      progression of their liver disease during follow-up. Among 50 patients without a
      known liver disease prior to the drug-induced liver injury, 10 had abnormal liver
      tests. Diagnostic work-up revealed alternative cause of liver disease in all
      except three patients (6%), who had asymptomatic abnormal liver tests (but normal
      bilirubin in all). CONCLUSIONS: Chronic abnormalities in liver tests, not
      explained by an identified liver disease, are very rare in patients previously
      diagnosed with drug-induced liver injury. This group of patients did not seem to
      have a clinically significant liver injury at long-term follow-up.

PMID- 17555425
TI  - The best candidates for transarterial chemotherapy in patients with
      hepatocellular carcinoma awaiting liver transplantation: a cohort-based
      characterization of dropout times.
AB  - BACKGROUND: Although transarterial chemotherapy is used to retard tumour
      progression for hepatocellular carcinoma (HCC) patients awaiting orthotopic liver
      transplantation (OLT), information regarding the acceptable waiting time and
      appropriate patient selection for the therapy is lacking. AIM: To examine dropout
      times and determine the best candidates for pre-transplant transarterial therapy
      in a cohort study. METHODS: In total, 180 consecutive HCC candidates receiving
      pre-transplant chemo-lipiodolization were included in the study. RESULTS:
      Overall, 70 (38.9%) patients dropped off the waiting list during the median
      follow-up of 19 months. According to the Child-Pugh (C-P) classification, the
      estimated dropout rates at 1 and 2 years were 17.2% and 44.8% for the C-P A group
      and 33.4% and 81.3% for the C-P B/C group, respectively. C-P B/C patients
      experienced more frequent dropouts than C-P A patients (P < 0.001). Risk factor
      analysis identified C-P classification to be the strongest predictor of dropout
      (P < 0.001). On multivariate analysis, alpha-fetoprotein (AFP) >100 ng/mL, tumour
      size >3 cm and multiple nodules remained independently predictive of dropout for
      C-P A group (all P < 0.05). Candidates with none of these factors were found to
      be at the lowest risk of dropout, with only a 22.5% dropout rate up to 41 months.
      CONCLUSIONS: This study suggests that Child-Pugh A patients with one nodule <3 cm
      and AFP < 100 ng/mL may be the best candidates for pre-transplant chemo
      lipiodolization, with the lowest dropout rate. However, comparative studies with
      other therapeutic options are needed to assess the definitive role of
      transarterial therapy in this setting.

PMID- 17555426
TI  - Determinants of the short-term gastric damage caused by NSAIDs in man.
AB  - BACKGROUND: The short-term gastric damage seen with non-steroidal anti
      inflammatory drugs (NSAIDs) in man may involve inhibition of cyclooxygenase (COX
      1) and COX-2 as well as the topical irritancy, which is dependant on the acidity
      (pKa) and/or lipophilicity (log P(7.4)). AIM: To study the quantitative
      relationship between NSAID-induced short-term gastric damage, their
      physicochemical properties and contrasting roles of COX-1 and COX-2 inhibition.
      METHODS: We identified studies that allowed a qualitative comparison of the
      gastric injury (Lanza scores) induced by NSAIDs with their pKa and log P(7.4).
      Damage was correlated with gastric COX inhibition and potency to inhibit COX-1
      and 2 and their COX-2/COX-1 selectivity ratio. RESULTS: The gastric damage
      correlates significantly with pKa (r = -0.69; P < 0.01), log P (r = -0.58, P <
      0.05) and potency of the NSAIDs to inhibit COX-1 (r = -0.61, P < 0.02), but not
      with COX-2 inhibition or COX-2/COX-1 selectivity. CONCLUSION: Against a
      background of COX-1 and COX-2 inhibition, the physicochemical properties of NSAID
      appear to play an important role in short-term gastric damage.

PMID- 17555427
TI  - Efficacy of mitemcinal, a motilin agonist, on gastrointestinal symptoms in
      patients with symptoms suggesting diabetic gastropathy: a randomized, multi
      center, placebo-controlled trial.
AB  - BACKGROUND: Mitemcinal, an oral motilin agonist, accelerates gastric emptying.
      AIM: To investigate if mitemcinal was superior to placebo in relief of symptoms
      attributed to gastroparesis. METHODS: In a randomized, double-blind design, 392
      insulin-requiring diabetics with symptoms attributable to gastroparesis were
      treated for 3 months with placebo, mitemcinal 5 or 10 mg bid. On a weekly basis,
      patients assessed whether there was adequate relief of their gastroparesis
      symptoms. Patients were classified as Complete Responders (CR) if there were
      three consecutive positive monthly responses, which required at least 50% of
      their weekly responses in a month being positive. An Overall Responder (OR) had
      at least 75% positive weekly responses for the whole treatment period. RESULTS:
      Mitemcinal 10 mg produced a significantly better response rate than placebo with
      a 10.6% increase in the OR (P < 0.05 vs. placebo). Mitemcinal 10 mg also produced
      statistically significant increases in the CR and OR in the subgroup identified
      by baseline body mass index (<35 kg/m(2)) and haemoglobin A(1c) (<10%) (P < 0.01
      vs. placebo). Adverse events did not differ from placebo frequency levels.
      CONCLUSIONS: Mitemcinal can induce a statistically significant response to
      treatment in a subset of diabetic gastroparesis where future prokinetic clinical
      trials should be focused.

PMID- 17555428
TI  - Intestinal chemo- and mechano-sensitivity: selective modification of small
      intestinal sensitivity by lipids.
AB  - BACKGROUND: Intestinal chemo-nociception is a recently described mechanism of
      perception of intraluminal stimuli that might involve pathways independent from
      mechano-nociception. AIM: To investigate whether intraluminal lipids not only
      modify mechano-sensitivity, but also influence chemo-sensitivity. METHOD:
      Nineteen healthy volunteers ingested an orojejunal tube assembly for mechanical
      and chemical stimulation of the proximal jejunum. Volume-controlled distension of
      a jejunal balloon and capsaicin perfusion were performed during simultaneous
      infusion of saline or a 10% lipid emulsion. A standard questionnaire evaluated
      quality and intensity of symptoms induced by intestinal stimulation. RESULTS:
      Balloon volumes to induce perception thresholds were significantly reduced during
      lipid perfusion (P < 0.05), while balloon pressures remained unaltered (P >
      0.05). Saline infusion (2.5 mL/min) did not alter thresholds of perception. Lipid
      infusion also increased intensity of perception during given distension volumes
      (P < 0.05). Lipid infusion did neither affect perception quality induced by
      capsaicin, nor perception thresholds, nor intensity of perception during
      capsaicin perfusion (P > 0.05). The quality of sensations induced by capsaicin
      perfusion was similar to sensations during distension, except of sensation of
      warmth, that was almost exclusively reported during capsaicin perfusion.
      CONCLUSIONS: Intraluminal lipids selectively modify intestinal mechano-perception
      and do not alter chemo-perception. Intestinal chemo-nociception and mechano
      nociception are two mechanisms of intestinal perception that involve distinct
      sensory pathways.

PMID- 17555429
TI  - Is MEDLINE alone enough for a meta-analysis?

PMID- 17555431
TI  - Subcellular localization of Escherichia coli osmosensory transporter ProP: focus
      on cardiolipin membrane domains.
AB  - The role for specific lipids in the spatial distribution of the membrane proteins
      and formation of the lipid-protein membrane domains is an emerging theme in the
      studies of the supramolecular organization of the bacterial cell. A combination
      of the lipid and protein visualization techniques with manipulation of the cell
      lipid composition provides a useful tool for these studies. This MicroCommentary
      reviews the first experimental example demonstrating an involvement of the
      phospholipid cardiolipin in recruitment of a membrane protein (specifically H(+)
      osmoprotectant symporter ProP) to the Escherichia coli cell poles. The properties
      of cardiolipin domains employed in creating a specific environment for structural
      organization and function of membrane protein complexes are also discussed.

PMID- 17555432
TI  - Competence-induced fratricide in streptococci.
AB  - Competence for natural genetic transformation in Streptococcus pneumoniae is
      controlled by the extracellular concentration of the competence-stimulating
      peptide (CSP), an exported peptide pheromone. Upon entering the competent state,
      pneumococci start transcribing a number of CSP-responsive genes, termed the early
      and late competence (com) genes. Some of the proteins encoded by these com genes
      are absolutely required for DNA uptake and transformation, but most of them are
      dispensable. This finding indicates that the majority of CSP-regulated proteins
      in S. pneumoniae is involved in processes unrelated to natural genetic
      transformation. Recently, however, it became clear that the biological role of a
      few of the dispensable proteins might be linked to the transformation process.
      Although these proteins are not needed for transformation per se, they constitute
      a killing mechanism that could be used by competent cells to acquire DNA from non
      competent pneumococci. This mechanism, termed fratricide, has so far only been
      described for pneumococci. In this manuscript, we review evidence that suggests
      the conservation of fratricide as well as the independent evolution of its
      genetic control and of its effectors in several species of the genus
      Streptococcus, and discuss its possible biological significance in relation to
      natural transformation.

PMID- 17555433
TI  - The Mycobacterium tuberculosis FAS-II condensing enzymes: their role in mycolic
      acid biosynthesis, acid-fastness, pathogenesis and in future drug development.
AB  - Mycolic acids are very long-chain fatty acids representing essential components
      of the mycobacterial cell wall. Considering their importance, characterization of
      key enzymes participating in mycolic acid biosynthesis not only allows an
      understanding of their role in the physiology of mycobacteria, but also might
      lead to the identification of new drug targets. Mycolates are synthesized by at
      least two discrete elongation systems, the type I and type II fatty acid
      synthases (FAS-I and FAS-II respectively). Among the FAS-II components, the
      condensing enzymes that catalyse the formation of carbon-carbon bonds have
      received considerable interest. Four condensases participate in initiation
      (mtFabH), elongation (KasA and KasB) and termination (Pks13) steps, leading to
      full-length mycolates. We present the recent biochemical and structural data for
      these important enzymes. Special emphasis is given to their role in growth,
      intracellular survival, biofilm formation, as well as in the physiopathology of
      tuberculosis. Recent studies demonstrated that phosphorylation of these enzymes
      by mycobacterial kinases affects their activities. We propose here a model in
      which kinases that sense environmental changes can phosphorylate the condensing
      enzymes, thus representing a novel mechanism of regulating mycolic acid
      biosynthesis. Finally, we discuss the attractiveness of these enzymes as valid
      targets for future antituberculosis drug development.

PMID- 17555434
TI  - Type VI secretion is a major virulence determinant in Burkholderia mallei.
AB  - Burkholderia mallei is a host-adapted pathogen and a category B biothreat agent.
      Although the B. mallei VirAG two-component regulatory system is required for
      virulence in hamsters, the virulence genes it regulates are unknown. Here we show
      with expression profiling that overexpression of virAG resulted in
      transcriptional activation of approximately 60 genes, including some involved in
      capsule production, actin-based intracellular motility, and type VI secretion
      (T6S). The 15 genes encoding the major sugar component of the homopolymeric
      capsule were up-expressed > 2.5-fold, but capsule was still produced in the
      absence of virAG. Actin tail formation required virAG as well as bimB, bimC and
      bimE, three previously uncharacterized genes that were activated four- to 15-fold
      when VirAG was overproduced. Surprisingly, actin polymerization was found to be
      dispensable for virulence in hamsters. In contrast, genes encoding a T6S system
      were up-expressed as much as 30-fold and mutations in this T6S gene cluster
      resulted in strains that were avirulent in hamsters. SDS-PAGE and mass
      spectrometry demonstrated that BMAA0742 was secreted by the T6S system when virAG
      was overexpressed. Purified His-tagged BMAA0742 was recognized by glanders
      antiserum from a horse, a human and mice, indicating that this Hcp-family protein
      is produced in vivo during infection.

PMID- 17555435
TI  - Variable switching rates of malaria virulence genes are associated with
      chromosomal position.
AB  - Antigenic variation in Plasmodium falciparum malaria is mediated by
      transcriptional switches between different members of the multicopy var gene
      family. Each var gene encodes a member of a group of heterogeneous surface
      proteins collectively referred to as PfEMP1. Mutually exclusive expression
      ensures that an individual parasite only transcribes a single var gene at a time.
      In this work we studied var gene switching to determine if transcriptional
      switches favour expression of particular subgroups of var genes and if var gene
      activation within a clonal population of parasites follows a predetermined order.
      We show that in clonal parasite populations, expression of var genes located in
      the central regions of chromosomes is remarkably stable and that they rarely
      undergo transcriptional switches in the absence of selection. In contrast,
      parasites expressing subtelomerically located var genes readily switched to
      alternative var loci. We confirmed these observations by generating transgenic
      parasites carrying drug selectable markers in subtelomeric and central var loci
      and monitoring switching after release from selection. Our data show that
      different var genes have different intrinsic switching rates that correlate with
      chromosomal location, and that there is no predetermined order of expression.

PMID- 17555437
TI  - Identification of a transcriptional regulator that controls intracellular gene
      expression in Salmonella Typhi.
AB  - Salmonella enterica serovar Typhi (S. Typhi), the aetiological agent of typhoid
      fever, is an exclusively human pathogen. Little is known about specific factors
      that may confer to this bacterium its unique pathogenic features. One of these
      determinants is CdtB, a homologue of the active subunit of the cytolethal
      distending toxin, which causes DNA damage leading to cell cycle arrest and
      distension of intoxicated cells. A unique property of S. Typhi CdtB is that it is
      only synthesized when this bacterium is within an intracellular compartment.
      Through a genetic screen, we have identified a transcriptional regulatory protein
      that controls the intracellular expression of cdtB. This regulator, which we have
      named IgeR, is a member of the DeoR family of transcriptional regulatory proteins
      and is highly conserved in all S. enterica serovars. IgeR directly binds the cdtB
      promoter and represses its expression in the extracellular environment.
      Microarray analysis identified additional IgeR-regulated genes that are involved
      in virulence. Constitutive expression of igeR resulted in the reduction of
      intracellular expression of cdtB by S. Typhi and in significant impairment of the
      virulence of Salmonella enterica serovar Typhimurium (S. Typhimurium) in mice. We
      propose that IgeR may co-ordinate gene expression during Salmonella's transition
      from an extracellular to an intracellular environment.

PMID- 17555436
TI  - Acquisition of a natural resistance gene renders a clinical strain of methicillin
      resistant Staphylococcus aureus resistant to the synthetic antibiotic linezolid.
AB  - Linezolid, which targets the ribosome, is a new synthetic antibiotic that is used
      for treatment of infections caused by Gram-positive pathogens. Clinical
      resistance to linezolid, so far, has been developing only slowly and has involved
      exclusively target site mutations. We have discovered that linezolid resistance
      in a methicillin-resistant Staphylococcus aureus hospital strain from Colombia is
      determined by the presence of the cfr gene whose product, Cfr methyltransferase,
      modifies adenosine at position 2503 in 23S rRNA in the large ribosomal subunit.
      The molecular model of the linezolid-ribosome complex reveals localization of
      A2503 within the drug binding site. The natural function of cfr likely involves
      protection against natural antibiotics whose site of action overlaps that of
      linezolid. In the chromosome of the clinical strain, cfr is linked to ermB, a
      gene responsible for dimethylation of A2058 in 23S rRNA. Coexpression of these
      two genes confers resistance to all the clinically relevant antibiotics that
      target the large ribosomal subunit. The association of the ermB/cfr operon with
      transposon and plasmid genetic elements indicates its possible mobile nature.
      This is the first example of clinical resistance to the synthetic drug linezolid
      which involves a natural resistance gene with the capability of disseminating
      among Gram-positive pathogenic strains.

PMID- 17555438
TI  - Unexpected effect of a Bacteroides conjugative transposon, CTnDOT, on chromosomal
      gene expression in its bacterial host.
AB  - Foreign DNA elements such as plasmids and conjugative transposons are constantly
      entering new bacterial hosts. A possible outcome of such events that has not been
      considered previously is that regulatory genes carried on some of them might
      affect the expression of chromosomal genes of the new host. To assess this
      possibility, we investigated the effect of the Bacteroides conjugative transposon
      CTnDOT on expression of chromosomal genes in Bacteroides thetaiotaomicron 5482
      (BT4001). Most of the upregulated genes were genes of unknown function, but a
      number of them were associated with a region of the chromosome that contained a
      putative conjugative transposon, which had been tentatively designated as CTn4
      bt. Upregulation of CTn4-bt genes and other chromosomal genes affected by CTnDOT
      was controlled by two regulatory genes on CTnDOT, rteA and rteB, which encode a
      two-component regulatory system. Transfer of CTn4-bt was also mediated by rteA
      and rteB. Three other putative CTns, CTn1-bt, CTn2-bt and CTn3-bt, were mobilized
      by CTnERL, a CTn closely related to CTnDOT, but genes from CTnERL other than rteA
      and rteB were also required. Unexpectedly, homologous recombination was required
      for CTn1-bt, CTn2-bt, CTn3-bt and CTn4-bt to integrate in the recipient. Our
      results show that regulatory genes on an incoming mobile element can have
      multiple effects on its new host, including the activation of previously non
      transmissible elements.

PMID- 17555439
TI  - Defining Candida albicans stationary phase by cellular and DNA replication, gene
      expression and regulation.
AB  - Stationary phase Candida albicans yeast cells harbour properties of better
      adherence, virulence and elevated drug resistance. C. albicans stationary phase
      is not well characterized in vitro either physiologically or molecularly. C.
      albicans yeast cells were grown in rich medium with 2% glucose. Based on growth
      and DNA profiles of cells, and by measurement of glucose and ethanol in the
      medium, we defined the timing of C. albicans entry into different growth
      transitions. We found that, compared with 24 h cells, mRNA content was less
      abundant in post-diauxic shift phase and even less in stationary phase C.
      albicans cells. Further analysis of the C. albicans transcriptome with
      oligonucleotide-based microarrays revealed that although the overall mRNA content
      had decreased, transcripts of many genes increased in post-diauxic shift phase as
      well as stationary phase. Genes involved in processes such as gluconeogenesis,
      stress resistance, adherence, DNA repair and ageing were expressed at higher
      levels at and beyond post-diauxic shift phase. Many C. albicans genes associated
      with virulence, drug resistance and cell-wall biosynthesis were expressed only at
      stationary phase. By screening 108 C. albicans transcription factor and cell-wall
      mutants we identified 17 genes essential for either entry or survival in
      stationary phase at 30 degrees C.

PMID- 17555440
TI  - Heterozygosity of genes on the sex chromosome regulates Candida albicans
      virulence.
AB  - In the mouse model for systemic infection, natural a/alpha strains of C. albicans
      are more virulent and more competitive than their spontaneous MTL-homozygous
      offspring, which arise primarily by loss of one chromosome 5 homologue followed
      by duplication of the retained homologue (uniparental disomy). Deletion of either
      the a or alpha copy of the MTL locus of natural a/alpha strains results in a
      small decrease in virulence, and a small decrease in competitiveness. Loss of the
      heterozygosity of non-MTL genes along chromosome 5, however, results in larger
      decreases in virulence and competitiveness. Natural MTL-homozygous strains are on
      average less virulent than natural MTL-heterozygous strains and arise by multiple
      mitotic cross-overs along chromosome 5 outside of the MTL region. These results
      are consistent with the hypothesis that a competitive advantage of natural
      a/alpha strains over MTL-homozygous offspring maintains the mating system of C.
      albicans.

PMID- 17555441
TI  - CsrA of Bacillus subtilis regulates translation initiation of the gene encoding
      the flagellin protein (hag) by blocking ribosome binding.
AB  - The global regulatory Csr (carbon storage regulator) and the homologous Rsm
      (repressor of secondary metabolites) systems of Gram-negative bacteria typically
      consist of an RNA-binding protein (CsrA/RsmA) and at least one sRNA that
      functions as a CsrA antagonist. CsrA modulates gene expression post
      transcriptionally by regulating translation initiation and/or mRNA stability of
      target transcripts. While Csr has been extensively studied in Gram-negative
      bacteria, until now Csr has not been characterized in any Gram-positive organism.
      csrA of Bacillus subtilis is the last gene of a flagellum biosynthetic operon. In
      addition to the previously identified sigma(D)-dependent promoter that controls
      expression of the entire operon, a sigma(A)-dependent promoter was identified
      that temporally controls expression of the last two genes of the operon (fliW
      csrA); expression peaks 1 h after cell growth deviates from exponential phase.
      hag, the gene encoding flagellin, was identified as a CsrA-regulated gene. CsrA
      was found to repress hag'-'lacZ expression, while overexpression of csrA reduces
      cell motility. In vitro binding studies identified two CsrA binding sites in the
      hag leader transcript, one of which overlaps the hag Shine-Dalgarno sequence.
      Toeprint and cell-free translation studies demonstrate that bound CsrA prevents
      ribosome binding to the hag transcript, thereby inhibiting translation initiation
      and Hag synthesis.

PMID- 17555442
TI  - Expression switching in the stevor and Pfmc-2TM superfamilies in Plasmodium
      falciparum.
AB  - Plasmodium falciparum possesses two multigenic families, var and rif, the
      products of which are expressed on the surface of infected erythrocytes, where
      via antigenic variation they contribute to malaria pathogenesis and evasion of
      antibody-mediated host immunity. The products of two smaller gene families,
      stevor and Pfmc-2TM, also localize to the erythrocyte membrane, although it is
      not known if they undergo antigenic switching. Herein we use gene-specific
      quantitative reverse transcription polymerase chain reaction (RT-PCR) to
      investigate the transcription pattern of the stevor and Pfmc-2TM gene families,
      in both primary and second generation clonal lines of the P. falciparum isolate,
      NF54. We show that: (i) the expression of stevor and Pfmc-2TM families is
      clonally variant, (ii) the expression of stevor and Pfmc-2TM families undergoes
      switching, and (iii) switching rates vary among different variants and different
      isogenic clones at rates higher than 2% per generation. In addition, we show that
      chromosomal telomeric deletions are common in clonal lines and result in a
      spectrum of deletion genotypes. These findings provide evidence that the stevor
      and Pfmc-2TM gene families play a role in P. falciparum antigenic variation.

PMID- 17555443
TI  - A novel lysis system in PM2, a lipid-containing marine double-stranded DNA
      bacteriophage.
AB  - In this study we investigated the lysis system of the lipid-containing double
      stranded DNA bacteriophage PM2 infecting Gram-negative marine Pseudoalteromonas
      species. We analysed wt and lysis-deficient phage-induced changes in the host
      physiology and ascribed functions to two PM2 gene products (gp) involved in
      lysis. We show that bacteriophage PM2 uses a novel system to disrupt the infected
      cell. The novelty is based on the following findings: (i) gp k is needed for the
      permeabilization of the cytoplasmic membrane and appears to play the role of a
      typical holin. However, its unique primary structure [53 aa, 1 transmembrane
      domain (TMD)] places it into a new class of holins. (ii) We have proposed that,
      unlike other bacteriophages studied, PM2 relies on lytic factors of the cellular
      origin for digestion of the peptidoglycan. (iii) gp l (51 aa, no TMDs) is needed
      for disruption of the outer membrane, which is highly rigidified by the divalent
      cations abundant in the marine environment. The gp l has no precedent in other
      phage lytic systems studied so far. However, the presence of open reading frame l
      like genes in genomes of other bacterial viruses suggests that the same system
      might be used by other phages and is not unique to PM2.

PMID- 17555444
TI  - Recent advances in the understanding of mastocytosis: the role of KIT mutations.
AB  - Mastocytosis is a heterogeneous disorder characterised by the expansion and
      accumulation of mast cells in different organs and tissues. Mast cell physiology
      is closely dependent on activation of the stem cell factor/Kit signalling
      pathways and accumulating evidences confirm the physiopathological key role of
      activating KIT mutations (typically D816V) in mastocytosis and their relationship
      with the clinical manifestations of the disease. This paper reviews the most
      recent advances in the understanding of the molecular mechanisms associated with
      KIT mutations in mastocytosis, including recent data about the use of new
      therapies targeting the Kit molecule and its associated downstream signalling
      pathways.

PMID- 17555445
TI  - A practical strategy for the routine use of BIOMED-2 PCR assays for detection of
      B- and T-cell clonality in diagnostic haematopathology.
AB  - BIOMED-2 polymerase chain reaction (PCR) assays for clonality analysis of
      immunoglobulin (IG) and T-cell receptor (TCR) gene rearrangements were evaluated
      in routine haematopathological practice where paraffin-embedded tissues
      constitute the majority of specimens. One hundred and twenty-five fresh/frozen
      and 316 paraffin specimens were analysed for DNA quality and clonality. Seventy
      nine per cent of paraffin specimens yielded PCR products of over 300 bp. These
      specimens and all fresh/frozen specimens were analysed with the complete set of
      BIOMED-2 reactions for IG (8 reactions) and/or TCR (6 reactions) gene
      rearrangements. The rate of detection of clonality was 96% in mature B-cell
      neoplasms and 98% in mature T-cell neoplasms and there were no significant
      differences in these rates between paraffin and fresh/frozen specimens. As the
      value of sole use of any individual BIOMED-2 reaction in clonality detection was
      limited, we assessed combinations of reactions that gave the greatest sensitivity
      with fewest reactions and were applicable for both fresh/frozen and paraffin
      specimens. For IG gene rearrangements, three reactions combining one targeting
      the IG heavy chain framework-2 region and two targeting the IG kappa locus
      achieved a 91% detection rate. For TCR gene rearrangements, the two TCR gamma
      reactions gave a 94% detection rate. We therefore recommend this strategy as the
      first-line assays for routine B- and T-cell clonality analysis in diagnostic
      haematopathology.

PMID- 17555446
TI  - Angioimmunoblastic T-cell lymphoma: histological progression associates with EBV
      and HHV6B viral load.
AB  - The clinical and histological presentations of angioimmunoblastic T-cell lymphoma
      (AITL) often mimic an infectious process. Epstein-Barr virus (EBV) and human
      herpes virus (HHV6) are known to be associated with AITL, but whether these viral
      infections play a role in its pathogenesis is unclear. It also remains to be
      investigated whether there might be other viruses associated with AITL. We first
      screened 26 well-characterised cases of AITL for herpesvirus by polymerase chain
      reaction (PCR) with universal primers and found evidence of only EBV and HHV6B
      infection. Subsequent PCR using virus-specific primers demonstrated EBV and HHV6B
      infection in 40/49 biopsies (36/42 cases) and 21/49 biopsies (19/42 cases) of
      AITL respectively with both viral infections found in 17/49 specimens (15/42
      cases). Importantly, simultaneous infection with both viruses was found only in
      specimens showing histological pattern II (n = 2) or III (n = 15). Interestingly,
      among specimens containing both viruses, there was a tendency towards an inverse
      correlation between the EBV and HHV6B viral load as shown by quantitative PCR. In
      specimens positive only for EBV, the viral load was significantly higher in
      specimens with histological pattern III than those with pattern II. High EBV load
      was also significantly associated with B-cell monoclonality. Double EBV encoded
      small RNA (EBER) in situ hybridisation and immunohistochemistry indicated that
      EBV-infected B cells had a late postgerminal centre immunophenotype. Our results
      demonstrate an association between EBV and HHV6B infection and the histological
      progression of AITL, suggesting that these viruses may play a role in the
      pathogenesis of this lymphoma.

PMID- 17555447
TI  - TLX1/HOX11 transcription factor inhibits differentiation and promotes a non
      haemopoietic phenotype in murine bone marrow cells.
AB  - The TLX/HOX11 subfamily of divergent homeobox genes are involved in various
      aspects of embryogenesis and, in the case of TLX1/HOX11 and TLX3/HOX11L2, feature
      prominently as oncogenes in human T-cell acute lymphoblastic leukaemia. TLX1
      possesses immortalising activity in a wide variety of blood cell lineages,
      however, the effect of this oncogene on haemopoietic cell differentiation has not
      been fully investigated. We therefore constitutively expressed TLX1 in murine
      bone marrow or fetal liver cells using retroviral transfer followed by
      transplantation and/or in vitro culture. TLX1 was found to dramatically alter
      haemopoiesis, promoting the emergence of a non-haemopoietic CD45(-) CD31(+) cell
      population while markedly inhibiting erythroid and granulocytic cell
      differentiation. To identify genetic programs perturbed by TLX1, a comparison of
      transcript profiles from J2E erythroid cells with and without enforced TLX1
      expression was undertaken. This revealed a pattern of gene expression indicative
      of enhanced proliferation coupled to differentiation arrest. Of the genes
      identified, two, KIT and VEGFC, were found to be potential TLX1 targets based on
      transcriptional assays. These results demonstrate that TLX1 can act broadly to
      impair haemopoiesis and divert differentiation to an alternative fate. This may
      account for its ability to promote the pre-leukaemic state via perturbation of
      specific gene expression programs.

PMID- 17555448
TI  - Mast cell infiltration is a favourable prognostic factor in diffuse large B-cell
      lymphoma.
AB  - Previous studies indicate that the inflammatory response in diffuse large B-cell
      lymphomas (DLBCL) is important for the clinical outcome. Mast cells are key
      regulators in this response; we investigated whether the number of tryptase
      positive mast cells is correlated with clinical outcome. Patients with many mast
      cells had a significantly better event-free survival (EFS) compared to those with
      few mast cells (P < 0.03 in both germinal centre (GC) and non-GC DLBCL. This
      supports the idea that the infiltration of mast cells is a reflection of the host
      inflammatory response and is related to a favourable outcome.

PMID- 17555449
TI  - Decreased TCR zeta-chain expression in T cells from patients with acquired
      aplastic anaemia.
AB  - In aplastic anaemia, T cells have a central role in the pathophysiology of bone
      marrow destruction. This study showed that T cells from patients with aplastic
      anaemia expressed decreased T-cell receptor (TCR) zeta-chain protein and mRNA
      levels compared to healthy controls. Patients with decreased TCR zeta-chain
      showed an abnormal response in intracellular calcium following stimulation
      through the TCR. We also observed an altered pattern of the transcription factors
      CREMalpha and Elf-1 that are implicated in zeta-chain transcription. We concluded
      that TCR zeta-chain expression was decreased in the majority of patients with
      aplastic anaemia, regardless of disease activity or treatment status.

PMID- 17555450
TI  - Two novel imatinib-responsive PDGFRA fusion genes in chronic eosinophilic
      leukaemia.
AB  - We identified two patients with a t(2;4)(p24;q12) and a t(4;12)(q2?3;p1?2),
      respectively, in association with BCR-ABL and FIP1L1-PDGFRA negative chronic
      eosinophilic leukaemia. Molecular analysis revealed a novel STRN-PDGFRA fusion
      for the t(2;4) and ETV6-PDGFRA for the t(4;12). The fusions were confirmed by
      specific amplification of the genomic breakpoints, reverse transcription
      polymerase chain reaction and fluorescence in situ hybridisation. Both patients
      were treated with imatinib and, following a rapid haematological response,
      achieved cytogenetic remission and a major molecular response. In conclusion,
      PDGFRA fuses to diverse partner genes in myeloid disorders. Identification of
      these fusions is important as they are particularly sensitive to imatinib.

PMID- 17555451
TI  - A novel approach to improving recombinant factor VIIa activity with a preserved
      platelet preparation.
AB  - Recombinant activated factor VII (NovoSeven, rFVIIa) is used to abrogate bleeding
      in haemophiliacs with inhibitors and is hypothesised to work by increasing
      activated factor X generation on the platelet surface. We hypothesised that
      rFVIIa activity could be increased by the co-addition of platelet procoagulant
      surface. This study characterised the ability of a rehydrated, lyophilised (RL)
      platelet preparation to increase rFVIIa activity in haemophilic conditions. RL
      platelets supported thrombin generation in the presence of factors VIII and IX
      but, in the absence of factors VIII and IX, thrombin generation was significantly
      reduced. RL platelets supported rFVIIa-mediated thrombin generation in a rFVIIa
      concentration dependent manner. In a cell-based in vitro model of haemophilia,
      the presence of RL platelets increased the rFVIIa-dependent thrombin generation
      rate 2.8-fold compared with rFVIIa alone. Similarly, the addition of RL platelets
      plus rFVIIa to the in vitro model of haemophilia and to haemophilic platelet-rich
      plasma shortened the onset of clot formation and increased clot stability in a
      fibrinolytic environment versus rFVIIa alone. These results suggest that RL
      platelets can support rFVIIa-mediated thrombin generation, and that co
      administration of RL platelets with rFVIIa may increase the efficacy of rFVIIa in
      some patients.

PMID- 17555452
TI  - Intensity of HLA class I expression and KIR-mismatch determine NK-cell mediated
      lysis of leukaemic blasts from children with acute lymphatic leukaemia.
AB  - The impact of human leucocyte antigen (HLA) class I expression intensity and
      killer-cell immunoglobulin-like receptor (KIR)-mismatch was investigated on
      natural killer (NK)-cell mediated lysis of B-lineage leukaemic blasts from 21
      paediatric patients in vitro. Blast susceptibility to standardised NK-activity
      and HLA-expression differed widely. A clear association between HLA
      molecules/cell (range 442 000-13 000) and specific lysis (mean 59%, range 13-98%)
      was observed (r(2) = 0.68). A compound model incorporating HLA-expression and KIR
      ligand-mismatch provided an even stronger association (r(2) = 0.87), whereas KIR
      ligand-mismatch alone was not significant. Assessment of these factors might
      identify patients who could benefit from NK-mediated graft-versus-leukaemia
      effects after mismatched stem cell transplantation.

PMID- 17555453
TI  - Association of bone marrow natural killer cell dose with neutrophil recovery and
      chronic graft-versus-host disease after HLA identical sibling bone marrow
      transplants.
AB  - Allogeneic bone marrow (BM) transplant (BMT) outcomes have been correlated with
      the infused nucleated, CD34(+), and T- cell dose. The potential impact of natural
      killer (NK) BM infused cell dose has however not been established. We analysed
      the outcomes of 78 patients receiving an HLA identical BMT. A higher NK cell dose
      was associated with the speed of neutrophil (P = 0.05) and platelet recovery (P =
      0.04). Higher nucleated cells, CD34(+), CD3(+), CD3(+)/4(+), CD3(+)/8(+) and NK
      cell dose were associated with a lower incidence of chronic GvHD (cGvHD) in
      univariate analysis. In multivariate analysis, the risk of cGvHD was increased by
      a lower NK cell dose [hazard ratio (HR) = 2.3 (1.2-4.4) for cell dose <0.9 x
      10(6)/kg; P = 0.01] and an older age [HR = 1.4 /10 years (1.1-1.8); P = 0.002].
      In addition, a higher CD3(+)/4(+) and NK cell dose were associated with a
      decreased incidence of viral infections (P = 0.03 and P = 0.06 respectively). No
      specific cell subpopulation infused dose was associated with survival. In
      conclusion, a higher BM NK cell dose is associated with an increased speed of
      neutrophil recovery and a decreased incidence of cGvHD.

PMID- 17555454
TI  - High risk of pregnancy-related venous thromboembolism in women with multiple
      thrombophilic defects.
AB  - Pregnancy is associated with an increased risk of venous thromboembolism, which
      probably varies according to the presence of single or multiple thrombophilic
      defects. This retrospective family cohort study assessed the risk of venous
      thromboembolism during pregnancy and puerperium, and the contribution of
      concomitant thrombophilic defects in families with hereditary antithrombin,
      protein C or protein S deficiencies. Probands were excluded. Of 222 female
      relatives, 101 were deficient and 121 non-deficient. Annual incidences of venous
      thromboembolism were 1.76% in deficient women versus 0.19% in non-deficient women
      [adjusted relative risk (RR) 11.9; 95% confidence interval (CI), 3.9-36.2]. Other
      single and multiple thrombophilic defects increased the risk in deficient women
      from 1.55% to 2.14% and 2.92%, and in non-deficient women from 0.16% to 0.09% and
      0.54% respectively. Deficient women were at lower risk (1.37%; 0.80-2.19) than
      deficient women that had never been pregnant (2.96%; 1.53-5.18); RR 0.5 (0.2
      0.99). This difference was due to the predominance of events related to oral
      contraceptives in deficient women that had never been pregnant (75%), while 71%
      of events in deficient women that had had at least one pregnancy were pregnancy
      related. In conclusion, women with hereditary deficiencies of antithrombin,
      protein C or protein S are at high risk of pregnancy-related venous
      thromboembolism. This risk is increased by multiple additional thrombophilic
      defects.

PMID- 17555456
TI  - Characterisation of a novel 49.3 kb Ggamma(Agamma delta beta)(0) -thalassaemia
      deletion in seven families of Asian descent.

PMID- 17555455
TI  - Incorporation of fibrin molecules containing fibrinopeptide A alters clot
      ultrastructure and decreases permeability.
AB  - Previous studies have shown that a heterozygous mutation in the fibrinogen Aalpha
      chain gene, which results in an Aalpha R16C substitution, causes fibrinolytic
      resistance in the fibrin clot. This mutation prevents thrombin cleavage of
      fibrinopeptide A from mutant Aalpha R16C chains, but not from wild-type Aalpha
      chains. However, the mechanism underlying the fibrinolytic resistance is unclear.
      Therefore, this study investigated the biophysical properties of the mutant
      fibrin that contribute to fibrinolytic resistance. Fibrin clots made from the
      mutant fibrinogen incorporated molecules containing fibrinopeptide A into the
      polymerised clot, which resulted in a 'spiky' clot ultrastructure with barbed
      fibrin strands. The clots were less stiff than normal fibrin and were cross
      linked slower by activated FXIII, but had an increased average fiber diameter,
      were more dense, had smaller pores and were less permeable. Protein sequencing
      showed that unclottable fibrinogen remaining in the supernatant consisted
      entirely of homodimeric Aalpha R16C fibrinogen, whereas both cleaved wild-type
      alpha chains and uncleaved Aalpha R16C chains were in the fibrin clot. Therefore,
      fibrinolytic resistance of the mutant clots is probably a result of altered clot
      ultrastructure caused by the incorporation of fibrin molecules containing
      fibrinopeptide A, resulting in larger diameter fibers and decreased permeability
      to fibrinolytic enzymes.

PMID- 17555457
TI  - Use of recombinant factor VIIa (rFVIIa) in the management of intractable
      haemorrhage: a survey of current UK practice.

PMID- 17555458
TI  - Persistence of the common Hartnup disease D173N allele in populations of European
      origin.
AB  - Hartnup disorder is an aminoaciduria that results from mutations in the recently
      described gene SLC6A19 on chromosome 5p15.33. The disease is inherited in a
      simple recessive manner and ten different mutations have been described to date.
      One mutation, the D173N allele, is present in 42% of Hartnup chromosomes from
      apparently unrelated families from both Australia and North America. We report an
      investigation of the origins of the D173N allele using a unique combination of
      variants including SNPs, microsatellites, and a VNTR across 211 Kb spanning the
      SLC6A19 locus. All individuals who carry the mutant allele share an identical
      core haplotype suggesting a single common ancestor, indicating that the elevated
      frequency of the D173N allele is not a result of recurrent mutation. Analyses of
      these data indicate that the allele is more than 1000 years old. We compare the
      reasons for survival of this allele with other major alleles in some other common
      autosomal recessive diseases occurring in European Caucasians. We postulate that
      survival of this allele may be a consequence of failure of the allele to
      completely inactivate the transport of neutral amino acids.

PMID- 17555459
TI  - Hepatocellular carcinoma: trends of incidence and survival in Europe and the
      United States at the end of the 20th century.
AB  - OBJECTIVES: There is large geographic variation in incidence levels and time
      trends of hepatocellular carcinoma. We compared population-based liver cancer
      incidence and survival in European and U.S. populations in order to elucidate
      geographic differences and time trends for these variables. METHODS: Since
      comparisons based on cancer registry data are problematic because of variations
      in liver cancer definition and coding, we considered a subset of cases likely to
      be mainly hepatocellular carcinoma, suitable for international comparison.
      Incidence and 5-yr relative survival were calculated from cases diagnosed in five
      European regions (30,423 cases) and the United States (6,976 cases) in 1982-1994.
      RESULTS: Age-standardized incidence was highest in southern Europe (12/100,000 in
      men and 3/100,000 in women in 1992-94) and lowest in northern Europe, where
      incidence was similar to that of the United States (3/100,000 in men, <1/100,000
      in women). Over the study period, incidence remained stable in the United States
      and most of Europe, except for a notable increase in southern Europe. Five-year
      relative survival was <10% in Europe, ranging from 8% (southern Europe) to 5%
      (eastern Europe), and 6% in the United States. Survival increased slightly with
      time, mainly in southern Europe and was unaffected by sex, but was better in
      younger patients. CONCLUSIONS: Increasing incidence in southern Europe is
      probably related to hepatitis B and C infection and increasing alcohol intake,
      while improving survival may be due to greater surveillance for cirrhosis. The
      survival gap between clinical and population-based series suggests management is
      better in centers of excellence.

PMID- 17555460
TI  - Ulcerative colitis: patient characteristics may predict 10-yr disease recurrence
      in a European-wide population-based cohort.
AB  - OBJECTIVES: Cumulative 10-yr relapse rates in ulcerative colitis (UC) of 70% to
      almost 100% have been reported in regional studies. The aim of this study was to
      determine the relapse rate in UC in a European population-based cohort 10 yr
      after diagnosis and to identify factors that may influence the risk of relapse.
      METHODS: From 1991 to 1993, 771 patients with UC from seven European countries
      and Israel were prospectively included in a population-based inception cohort and
      followed for 10 yr. A relapse was defined as an increase in UC-related symptoms
      leading to changes in medical treatment or surgery. The cumulative relapse rate,
      time to first relapse, and number of relapses in the follow-up period were
      recorded and possible causative factors were investigated. RESULTS: The
      cumulative relapse rate of patients with at least one relapse was 0.67 (95% CI
      0.63-0.71). The time to first relapse showed a greater hazard ratio (HR) (1.2, CI
      1.0-1.5) for women and for patients with a high level of education (1.4, CI 1.1
      1.8). The number of relapses decreased with age, and current smokers had a lower
      relapse rate (0.8, CI 0.6-0.9) than nonsmokers. The relapse rate in women was 1.2
      (CI 1.1-1.3) times higher than in men. An inverse relation was found between the
      time to the first relapse and the total number of relapses. CONCLUSION: In 67% of
      patients, there was at least one relapse. Smoking status, level of education, and
      possibly female gender were found to influence the risk of relapse.

PMID- 17555461
TI  - Value of serum IgG4 in the diagnosis of autoimmune pancreatitis and in
      distinguishing it from pancreatic cancer.
AB  - OBJECTIVES: To determine the sensitivity and specificity of elevated serum IgG4
      level for the diagnosis of autoimmune pancreatitis (AIP) and its ability to
      distinguish AIP from pancreatic cancer, its main differential diagnosis. METHODS:
      We measured serum IgG4 levels (normal 8-140 mg/dL) in 510 patients including 45
      with AIP, 135 with pancreatic cancer, 62 with no pancreatic disease, and 268 with
      other pancreatic diseases. RESULTS: Sensitivity, specificity, and positive
      predictive values for elevated serum IgG4 (>140 mg/dL) for diagnosis of AIP were
      76%, 93%, and 36%, respectively, and 53%, 99%, and 75%, respectively, for IgG4 of
      >280 mg/dL. Among subjects with elevated IgG4, non-AIP subjects (N = 32) differed
      from AIP subjects (N = 34) in that they were more likely to be female (45%vs 9%,
      P < 0.001), less likely to have serum IgG4 >280 mg/dL (13%vs 71%, P < 0.001), or
      elevation of total IgG (16%vs 56%, P < 0.001). Serum IgG4 levels were elevated in
      13/135 (10%) pancreatic cancer patients; however, only 1% had IgG4 levels >280
      mg/dL compared with 53% of AIP. Compared with AIP, pancreatic cancer patients
      were more likely to have CA19-9 levels of >100 U/mL (71%vs 9%, P < 0.001).
      CONCLUSION: Elevated serum IgG4 levels are characteristic of AIP. However, mild
      (<2-fold) elevations in serum IgG4 are seen in up to 10% of subjects without AIP
      including pancreatic cancer and cannot be used alone to distinguish AIP from
      pancreatic cancer. Because AIP is uncommon, IgG4 elevations in patients with low
      pretest probability of having AIP are likely to represent false positives.

PMID- 17555462
TI  - National underuse of anti-thrombotic therapy in chronic atrial fibrillation
      identified from digoxin prescribing.
AB  - AIMS: To examine if appropriate antithrombotic therapy in atrial fibrillation is
      implemented nationally. METHODS: Using prescriptions for digoxin as a surrogate
      for atrial fibrillation, we identified its coprescription with antithrombotic
      therapy, aspirin or warfarin in a national prescribing database in 27 571
      patients over 45 years old. RESULTS: Proportionately significantly more men were
      on warfarin, and use in those >75 years old was three times less than in those
      <65 years. Reluctance to use antithrombotics was confirmed in a postal survey.
      CONCLUSION: Data suggest a missed opportunity to prevent stroke with women and
      those >75 years old least likely to receive warfarin.

PMID- 17555463
TI  - Multiple-dose pharmacokinetics of peginterferon alfa-2b in patients with renal
      insufficiency.
AB  - AIM: To evaluate the safety, tolerability and multiple-dose pharmacokinetics of
      pegylated interferon (PEG-IFN) alfa-2b in patients with moderate or severe renal
      insufficiency and in those with normal renal function. METHODS: In an open-label
      study, subjects with normal renal function (creatinine clearance >80 ml min(-1)
      per 1.73 m2) and patients with moderate (30-50 ml min(-1) per 1.73 m2) or severe
      (10-29 ml(-1) min(-1) per 1.73 m2) renal impairment received weekly injections of
      PEG-IFN alfa-2b (1.0 microg kg(-1)) for 4 weeks. Safety assessments were made
      before each injection and blood samples were taken up to 168 h after the final
      dose. RESULTS: Renal insufficiency increased PEG-IFN alfa-2b exposure. Area under
      the curve for 0-tau (dosing interval of 168 h), AUC(tau), was increased 30% and
      120% in patients with moderate or severe renal insufficiency, respectively. Mean
      maximum serum concentration was almost doubled in patients with severe
      insufficiency [1305.8 pg ml(-1); 95% confidence interval (CI) 825, 1786] compared
      with subjects with normal renal function (731.4 pg ml(-1); 95% CI 407, 1056),
      whereas the apparent volume of distribution was reduced (0.80 l kg(-1)vs. 1.28 l
      kg(-1), respectively). Elimination half-life was extended in patients with
      moderate and severe renal insufficiency (65.6 h and 64.9 h, respectively)
      compared with subjects with normal renal function (51.5 h). Significant
      differences were observed in the AUC and C(max) values of patients with severe
      renal dysfunction, compared with those who had normal renal function (P < 0.05;
      Kruskal-Wallis test). PEG-IFN alfa-2b was well tolerated and adverse events were
      similar in both treatment groups. CONCLUSIONS: Exposure to PEG-IFN alfa-2b is
      increased in patients with renal insufficiency, suggesting that doses of the drug
      should be reduced by 50% in patients with severe renal insufficiency and by 25%
      in those with moderate insufficiency.

PMID- 17555464
TI  - Polonium-210 in news: an allegory of a misappropriated science.

PMID- 17555465
TI  - Pharmacokinetics, safety, and efficacy of mycophenolate mofetil in combination
      with sirolimus or ciclosporin in renal transplant patients.
AB  - AIMS: To compare the pharmacokinetics of mycophenolic acid (MPA) and its
      metabolite (MPAG) when mycophenolate mofetil (MMF) is administered in combination
      with sirolimus or ciclosporin (CsA) in renal allograft recipients. Safety and
      efficacy (biopsy-proven acute rejection (BPAR)) were also assessed. METHODS:
      Patients (n = 45) were randomized 2 : 1 to receive treatment with sirolimus (n =
      30; dosed to maintain trough concentrations of 10-25 ng ml(-1) until week 8, and
      then 8-15 ng ml(-1) thereafter) or CsA (n = 15; administered as per centre
      practice) both in combination with daclizumab, oral MMF and corticosteroids.
      Pharmacokinetic assessments were performed at day 7, week 4, and months 3 and 6
      post-transplant. The primary endpoint was the AUC(0,12 h) for MPA and MPAG. The
      pharmacokinetics of sirolimus were also assessed. RESULTS: MPA exposure was 39
      50% lower (month 6 mean AUC(0,12 h) (95%CI): 40.4 (33.8, 47.0) vs. 68.5 (54.9,
      82.0) microg ml(-1) h) and MPAG exposure was 25-52% higher (722 (607, 838) vs.
      485 (402, 569) microg ml(-1) h at month 6) in the presence of CsA compared with
      sirolimus across visits. BPAR was 40.0% with sirolimus and 13.3% with CsA. The
      incidence of hypertension, tremors and hirsutism was higher with CsA than with
      sirolimus, while the incidence of diarrhoea, hyperlipidaemia and impaired wound
      closure was higher with sirolimus. No deaths, malignancies or graft losses were
      reported. CONCLUSIONS: Co-administration of sirolimus with MMF led to greater MPA
      exposure, but lower MPAG exposure, than co-administration with CsA. As rejection
      rates were higher in the absence of CsA, further study of calcineurin inhibitor
      free regimens is required before general recommendations can be made.

PMID- 17555466
TI  - A re-evaluation of kava (Piper methysticum).

PMID- 17555467
TI  - Limited influence of UGT1A1*28 and no effect of UGT2B7*2 polymorphisms on UGT1A1
      or UGT2B7 activities and protein expression in human liver microsomes.
AB  - AIMS: UGT1A1 and UGT2B7 are enzymes that commonly contribute to drug
      glucuronidation. Since genetic factors have been suggested to contribute to
      variability in activities and expression levels of these enzymes, a quantitative
      assessment of the influence of the major genotypes (UGT1A1*28 or UGT2B7*2) on
      enzyme activities was conducted. METHODS: Using a bank of microsomal samples from
      59 human livers, the effect of UGT1A1*28 or UGT2B7*2 polymorphisms were
      investigated on rates of estradiol 3-glucuronidation (a marker of UGT1A1 enzyme
      activity) or zidovudine glucuronidation (a marker of UGT2B7 enzyme activity) and
      levels of immunoreactive protein for each enzyme. Glucuronidation rates for both
      enzymes were measured at K(m)/S(50) and 10 times K(m)/S(50) concentrations.
      RESULTS: UGT1A1 and UGT2B7 enzyme activities varied up to 16-fold and sixfold,
      respectively. Rates at K(m)/S(50) concentration closely correlated with rates at
      10 times K(m)/S(50) concentration for both enzymes (but not at 1/10th K(m) for
      UGT2B7). Enzyme activities correlated with relative levels of immunoreactive
      protein for UGT1A1 and UGT2B7. Furthermore, rates of zidovudine glucuronidation
      correlated well with rates of glucuronidation of the UGT2B7 substrate gemcabene,
      but did not correlate with UGT1A1 enzyme activities. For the UGT1A1*28
      polymorphism, consistent with levels of UGT1A1 immunoreactive protein, mean
      UGT1A1 activity was 2.5- and 3.2-fold lower for TA(6)/TA(7) (P < 0.05) and
      TA(7)/TA(7) (P < 0.001) genotypes in comparison with the TA(6)/TA(6) genotype.
      CONCLUSIONS: Relative to the observed 16-fold variability in UGT1A1 activity,
      these data indicate only a partial (approximately 40%) contribution of the
      UGT1A1*28 polymorphism to variability of interindividual differences in UGT1A1
      enzyme activity. For the UGT2B7*2 polymorphism, genotype had no influence on
      immunoreactive UGT2B7 protein or the rate of 3'-azido-3'-deoxythymidine
      glucuronidation.

PMID- 17555468
TI  - What therapies have replaced rofecoxib in Ireland?
AB  - AIMS: To examine prescription patterns of nonsteroidal anti-inflammatory drugs
      (NSAIDs) or analgesics in patients prescribed chronic rofecoxib treatment prior
      to withdrawal from the Irish market, and to determine the impact on proton pump
      inhibitor (PPI) co-prescription. METHODS: Using a national prescribing database,
      adults (> or =16 years) prescribed rofecoxib for > or =3 months, but not
      analgesics, from January to September 2004 were identified. A longitudinal
      prescribing history was used to determine switching patterns to other
      cyclooxygenase (COX)-2 inhibitors, NSAIDs or analgesics during 3 and 12 months
      after withdrawal. Concomitant PPI prescription was examined. Logistic regression
      was used to determine the likelihood of switching to a COX-2 inhibitor vs.
      nonselective NSAID and factors influencing concomitant PPI prescription. RESULTS:
      After rofecoxib withdrawal, 30.2% (1558) and 17.9% (922) of the 5155 study
      subjects received no further NSAID prescription during 3 and 12 months,
      respectively. During the 12-month period, approximately one-third of NSAID
      prescriptions were for <3 months; 40.7% (2096) received sequential prescriptions
      for different NSAIDs. Co-prescription of analgesics occurred in 49.3% (2539) of
      subjects. Neither age nor gender influenced the type of NSAID prescribed in the
      12 months post rofecoxib withdrawal. PPI prescription increased by 5.5% during
      the study, associated with use of nonselective NSAIDs, prior use of PPIs and
      increasing age. CONCLUSIONS: The majority of those receiving chronic rofecoxib
      therapy were prescribed either no further NSAID or short-term NSAID therapy only
      during the 12 months post withdrawal, which suggests the subsequent controversy
      may have encouraged prescribers to adhere more closely to published guidelines.

PMID- 17555469
TI  - The influence of continuous venovenous haemodialysis on the pharmacokinetics of
      multiple oral moxifloxacin administration to patients with severe renal
      dysfunction.
AB  - AIM: We investigated single dose and steady-state pharmacokinetics of
      moxifloxacin in eight venovenous haemodialysis patients. METHODS: Plasma,
      dialysate and urine pharmacokinetic parameters for moxifloxacin and its main
      metabolites were calculated after single and multiple (7 days) dosing with 400 mg
      day(-1). RESULTS: Moxifloxacin pharmacokinetics after a single dose and at steady
      state (multidose day 7) were comparable in patients with impaired renal function
      and healthy subjects (geometric mean/%CV AUC mg l(-1) h single dose 37.0/24.3 in
      haemodialysis patients vs. 29.8/22.6 in healthy subjects, 95% CI for ratio of
      haemodialysis patients to healthy subjects 99.34%, 154.60%; steady state
      40.4/29.1 haemodialysis patients vs. 33.9/20.1 in healthy subjects, 95% CI for
      ratio of haemodialysis patients to healthy subjects 90/39%, 156.93%). In
      haemodialysis patients plasma concentrations of moxifloxacin at steady-state were
      elevated compared with those after a single 400 mg dose (AUC mg l(-1) h,
      geometric mean/%CV, 40.4/29.1) compared with 37.0/24.3; 95% CI for ratio of
      steady-state to single dose 87.29%, 136.52%, as were concentrations of metabolite
      M1 3.21/34.6 compared with 2.02/45.3, 95% CI for ratio of steady state to single
      dose 14.21%, 175.07%. Haemodialysis cleared about 9% of the dose as unchanged
      moxifloxacin. CONCLUSIONS: No dose adjustments are required for venovenous
      haemodialysis patients on oral moxifloxacin therapy.

PMID- 17555470
TI  - Reactive perivascular T-cell infiltrate predicts survival in primary central
      nervous system B-cell lymphomas.
AB  - Well-established histopathological prognostic factors are lacking in primary
      central nervous system (CNS) lymphomas (PCNSL). The present study investigated
      the presence and prognostic role of tumour necrosis (TN) and reactive
      perivascular T-cell infiltrate (RPVI), defined as a rim of small reactive T
      lymphocytes occurring alone or located between the vascular wall and large
      neoplastic cells, in tumour samples from 100 immunocompetent patients with PCNSL.
      World Health Organization histotypes of the patients were: 96 diffuse large B
      cell lymphomas, two Burkitt-like lymphomas, one anaplastic large T-cell lymphoma
      and one unclassified B-cell lymphoma. TN was observed in 24 (24%) cases and RPVI
      in 26 (36%) of 73 assessable cases. Patients with RPVI-positive lesions exhibited
      a significantly better overall survival (OS) than patients with RPVI-negative
      lymphoma, particularly among patients treated with high-dose methotrexate-based
      chemotherapy (3-year OS: 59 +/- 14% vs. 42 +/- 9%, P = 0.02). By contrast, the
      presence of TN did not demonstrate prognostic significance. Multivariate analysis
      confirmed an independent association between RPVI and survival. In conclusion,
      the presence of RPVI is independently associated with survival in PCNSL. This
      parameter can be easily and routinely assessed at diagnosis on histopathological
      specimens.

PMID- 17555471
TI  - Aberrant nuclear p53 protein expression detected by immunohistochemistry is
      associated with hemizygous P53 deletion and poor survival for multiple myeloma.
AB  - Hemizygous TP53 deletion is an adverse risk factor in multiple myeloma (MM) but
      its relationship with p53 protein expression is unclear. We investigated 105
      newly diagnosed myeloma patients and correlated nuclear p53 protein
      immunoreactivity with TP53 deletion status, myeloma-associated genetic risk
      factors and survival. Fluorescence in situ hybridisation (FISH) detected
      hemizygous TP53 deletions in 13 (12%) patients while immunohistochemistry
      detected nuclear p53 protein expression in 12 (11%). Ten (77%) of the 13
      del(TP53) cases expressed nuclear p53 protein while 10 (83%) of the 12 nuclear
      p53 immunoreactive cases had hemizygous TP53 deletions. Hemizygous TP53 deletion
      and p53 protein expression were strongly correlated (P < 0.001). The overall
      survival of patients with p53 protein expression was significantly shorter than
      that of patients without p53 expression (P < 0.001). A multivariate analysis
      including other myeloma-associated genetic risk factors confirmed p53 expression
      as an independent risk factor for survival. Our data indicate that nuclear p53
      protein expression, detected by a widely available immunohistochemical method, is
      strongly associated with TP53 deletion and an adverse clinical outcome for MM.

PMID- 17555472
TI  - Platelet morphology, platelet mass, platelet count and prognosis in patients with
      myelodysplastic syndromes.

PMID- 17555473
TI  - Bladder and urethral function in pelvic organ prolapsed lysyl oxidase like-1
      knockout mice.
AB  - OBJECTIVES: To examine bladder and urethral function in pelvic organ prolapsed
      lysyl oxidase like-1 (LOXL1) knockout mice. MATERIALS AND METHODS: Female parous
      Loxl1 (-/-) mice in the stable phase of prolapse, and age-matched wild type (WT)
      mice (six each) had conscious cystometry, leak-point pressure (LPP) testing, and
      contractile responses assessed of their bladder muscle strips to KCl, electrical
      field stimulation, ATP, and carbachol. RESULTS: Loxl1 (-/-) mice voided more
      frequently and had lower mean (sem) bladder capacity, at 0.10 (0.01) vs 0.20
      (0.01) mL, and voiding pressure, at 25.0 (1.90) vs 36.6 (4.04) cmH(2)O,
      respectively, during cystometry than had WT mice. The LPP was not significantly
      different between WT and Loxl1 (-/-) mice, at 7.05 (0.81) vs 5.22 (1.23) cmH(2)O,
      respectively. There were no significant differences between bladder strips from
      Loxl1 (-/-) mice and WT mice in their responsiveness to various stimuli.
      CONCLUSIONS: Loxl1 (-/-) knockout mice had lower urinary tract dysfunction, most
      likely due to urethral dysfunction. Loxl1 (-/-) knockout mice can be used as an
      animal model for pelvic floor disorders. Further studies are needed to
      characterize the morphological and molecular alterations of the bladder and
      urethra.

PMID- 17555474
TI  - The association of time of day and serum testosterone concentration in a large
      screening population.
AB  - OBJECTIVE: To assess testosterone patterns during clinical hours in a large
      population of men participating in a national screening programme for prostate
      cancer, as the effect of time of day on serum testosterone concentration is
      unclear and largely reported in small studies. SUBJECTS AND METHODS: Testosterone
      levels were measured in 3006 men attending the national Prostate Cancer Awareness
      Week screening programme. Blood samples were obtained between 06.00 and 18.00
      hours, whenever men presented for screening. All men completed questionnaires on
      age, comorbidities, height and weight. Testosterone levels were compared based on
      four periods, i.e. T1, 06.00-10.00 (632 men), T2, 10.00-12.00 (812), T3, 12.00
      14.00 (388), and T4, 14.00-18.00 hours (1174). RESULTS: The mean (sd, range) age
      of the men was 60.3 (9.9, 40-94) years and the mean (sd) testosterone level was
      415.2 (190.9) ng/dL. There was no change in mean (sd) testosterone levels over
      T1, T2 and T3, at 444.9 (206.2), 433.5 (195.8) and 434.4 (181.2) ng/dL,
      respectively, but levels at T4, at 380.4 (176.4) ng/dL, were lower by
      approximately 13% (P < 0.05). Advancing age, diabetes and obesity were associated
      with lower testosterone levels. The percentage of men with biochemical
      hypogonadism (<300 ng/dL) did not change across all four periods. CONCLUSIONS:
      Testosterone levels in older men are stable throughout the morning and early
      afternoon, declining only modestly thereafter. Further case-controlled studies
      are needed to confirm these findings.

PMID- 17555475
TI  - Microvascular tumour invasion in renal cell carcinoma: the most important
      prognostic factor.
AB  - OBJECTIVE: To evaluate the role of microvascular invasion (MVI) in the primary
      lesion for predicting tumour behaviour in patients with renal cell carcinoma
      (RCC), as reliable clinical prognostic factors would be very valuable. PATIENTS
      AND METHODS: MVI was assessed in 230 patients with clinically localized RCC
      (stages T1-4NxM0) who had a radical nephrectomy and/or nephron-sparing surgery.
      The median (range) follow-up was 48 (3-130) months. The impact of MVI on disease
      progression and its correlation with clinical and histopathological factors was
      analysed, including whether patients were symptomatic or not at presentation,
      Fuhrman nuclear grade, tumour size, pathological stage and lymph node metastasis.
      Regression analyses and survival curves were used to determine if MVI was
      associated with the prognosis of RCC. RESULTS: There was MVI in 59 patients
      (26%); of these, 46% developed disease recurrence. Among the 171 patients with no
      MVI, only 11 (6%) had tumour recurrence. MVI was associated with tumour diameter,
      nuclear grade, pathological stage, lymph node metastasis and the presence of
      sarcomatous elements in the tumour. Multivariate analysis showed that MVI was an
      independent predictor of disease recurrence and the most important factor related
      to death. CONCLUSION: MVI is an independent predictor of prognosis in patients
      with RCC.

PMID- 17555476
TI  - Prognostic significance of p27Kip1 expression in bladder cancer.
AB  - The importance of markers in urological cancer is well recognised and many
      attempts are being made to find one which will be of prognostic significance.
      Authors from New York found that low expression of p27Kip1 in patients with
      bladder cancer was a significant predictor of pelvic recurrence, progression to
      metastasis and death. Authors from Switzerland examined patients with a primary
      solitary distal ureteric TCC; they found that distal ureteric resection in such
      patients is feasible, and that the long-term oncological outcome appears to be
      comparable to more radical treatment of this condition. OBJECTIVE: To define the
      prognostic significance of p27(Kip1) expression in bladder cancer for overall,
      disease-specific, metastasis-free and pelvic recurrence-free survival, and to
      identify clinical and pathological correlates of p27(Kip1) immunophenotypes.
      PATIENTS AND METHODS: Tumour samples from 128 evaluable patients with bladder
      cancer were assessed by immunohistochemistry for p27(Kip1) and E2F-1 expression.
      Immunoreactivity of p27(Kip1) was correlated with clinicopathological variables,
      E2F-1 immunoreactivity, and outcome. Multivariate analysis was used to assess
      predictors of outcome. The median follow-up was 30.9 months overall and 105.7
      months in the 32 patients alive at the last follow-up. RESULTS: The fraction of
      tumour cells with p27(Kip1) nuclear immunoreactivity was <5% in 15, 5-25% in 30,
      25-50% in 19, 50-75% in 51, and > or = 75% in 13 patients. High-grade tumours and
      those with lower E2F-1 nuclear reactivity had a lower mean percentage p27(Kip1)
      reactivity (P = 0.047 and 0.011, respectively). On multivariate analysis, the
      percentage p27(Kip1) reactivity was a significant independent predictor of pelvic
      recurrence (P = 0.017), progression to metastases (P = 0.046), death from disease
      (P = 0.008), and death from any cause (P = 0.017), with a low expression
      portending a worse prognosis. Suspicion of vascular invasion was a significant
      independent predictor of progression to metastases (P = 0.002), death from
      disease, and death from any cause (both P < 0.001). Lymph node involvement was a
      significant independent predictor of progression to metastases (P = 0.006).
      CONCLUSIONS: Low expression of p27(Kip1) was a significant independent predictor
      of pelvic recurrence, progression to metastasis, death from disease and death
      from any cause, in patients with bladder cancer.

PMID- 17555477
TI  - Gadolinium use in patients with kidney disease: a cause for concern.
AB  - Gadolinium is widely used as a magnetic resonance imaging contrast agent and is
      considered to have a good overall safety profile. Recently, both renal and extra
      renal toxicities have been reported following exposure to gadolinium in patients
      with underlying kidney disease. Gadolinium-related contrast-induced nephropathy
      appears to be a risk in patients with advanced kidney disease and especially
      those with diabetic nephropathy. Even more concerning is the strong association
      of gadolinium with nephrogenic systemic fibrosis (NSF), a devastating fibrosing
      disorder of the skin and other systemic organs. Although cause and effect have
      not been proven for the NSF-gadolinium link, the impaired renal elimination of
      gadolinium in patients with kidney disease and the instability of gadolinium
      chelate binding may expose tissues to toxic free Gd(3+) and promote this
      fibrosing disorder. Caution should be exercised when utilizing gadolinium as a
      contrast agent in patients with advanced CKD or ESRD.

PMID- 17555478
TI  - Is there a role for bisphosphonates in chronic kidney disease?
AB  - Patients with stage 5 chronic kidney disease (CKD) including those on dialysis
      can and do develop osteoporosis. They also develop a wide range of other
      metabolic bone diseases that may look like osteoporosis when it is defined by
      either the World Health Organization bone mineral density (BMD) criteria or by
      the development of fragility fractures. Those dialysis patients with osteoporosis
      that is due to gonadal hormone deficiency such as postmenopausal osteoporosis,
      glucocorticoid-induced osteoporosis, or male osteoporosis may benefit from the
      administration of bisphosphonates (BPs). The challenges lie in the diagnosis of
      osteoporosis in this population where adynamic, osteomalacic, hyperparathyroid,
      or aluminum bone disease are also prevalent, with concommitant low BMD and low
      trauma fractures, but where BPs may be contraindicated. The only secure means to
      diagnose osteoporosis in this patient population is by quantitative bone
      histomorphometry demonstrating low trabecular bone volume and disrupted
      microarchitecture. Once the diagnosis of osteoporosis is established, BPs should
      be considered for a well-defined brief period of time (e.g., 2-3 years), even
      though there is no evidence for a fracture reduction benefit in this population.
      If a BP is chosen there may be a need for dose adjustment or slower infusion
      rates (for the intravenous formulations), as a greater bone retention may occur
      for these renally cleared agents. While it is unknown what consequences could
      develop from increased bone retention in patients with little renal function,
      data are needed if more bone retention of BP might lead to a greater risk of the
      development of adynamic bone disease and lower bone strength. More data are
      needed to define the risks and benefits of BPs in patients with stage 5 CKD.

PMID- 17555480
TI  - Withholding and withdrawal from dialysis: what we know about how our patients
      die.
AB  - Withholding and withdrawal of dialysis has been a reality since dialysis was
      invented. Only in the past 20 years has it been formally studied, and we still
      have a great deal to learn. The nephrology community has slowly come to accept
      that, for some of our patients, not having dialysis is a better option than
      continuing or initiating therapy. The principles of palliative care throughout
      the disease trajectory and hospice care at end of life are germane to this
      population due to its high symptom burden and mortality rate. We review what is
      currently known concerning patients who choose to withhold or withdraw from
      dialysis, and the current barriers (and solutions) to providing them with optimal
      palliative care.

PMID- 17555479
TI  - Managing bone parameters in dialysis patients: international guideline conflicts.
AB  - The linkage between bone parameters (calcium, phosphate, parathyroid hormone) and
      cardiovascular death in dialysis patients has led to a major resurgence in
      interest in this area of nephrological practice. Two major groups have recently
      published extensive guidelines for clinical practice in this area--the National
      Kidney Foundation's Kidney Disease Outcomes and Quality Initiative from the
      United States, and the Caring for Australasians with Renal Impairment group from
      Australia and New Zealand. There are some important differences in their
      recommendations, which reflect variations in local clinical practice,
      reimbursement systems, and interpretation of the medical literature. Two areas of
      divergence are highlighted in this editorial--use of vitamin D and its analogs,
      and use of phosphate binders. Readers of guidelines such as these need to be
      careful to interpret such recommendations in the context of the realities of
      their local clinical practice and availability of therapies.

PMID- 17555481
TI  - Why is the evidence favoring hemodialysis over peritoneal dialysis misleading?

PMID- 17555485
TI  - Quality of life assessments in hemodialysis and peritoneal dialysis patients: an
      important dimension of patient choice why is the evidence favoring hemodialysis
      over peritoneal dialysis misleading?

PMID- 17555486
TI  - Randomized control trial versus retrospective data.

PMID- 17555487
TI  - Recognition, treatment, and prevention of propylene glycol toxicity.
AB  - Propylene glycol is a commonly used solvent for oral, intravenous, and topical
      pharmaceutical preparations. Although it is considered safe, large intravenous
      doses given over a short period of time can be toxic. Underlying renal
      insufficiency and hepatic dysfunction raise risk for toxicity. Toxic effects
      include hyperosmolality, increased anion gap metabolic acidosis (due to lactic
      acidosis), acute kidney injury, and sepsis-like syndrome. Treatment of toxicity
      includes hemodialysis to effectively remove propylene glycol. Prevention is best
      achieved by limiting the dose of propylene glycol infused.

PMID- 17555488
TI  - The acute cardiac effects of dialysis.
AB  - It is well recognized that the procedure of hemodialysis is associated with
      significant changes in blood pressure and systemic hemodynamics; 20-30% of
      treatments are complicated by intradialytic hypotension (IDH). There are now an
      increasing number of studies using electrocardiographic, isotopic and
      echocardiographic techniques that show that subclinical myocardial ischemia
      occurs during dialysis. This concept is supported by some studies showing that
      dialysis can induce acute rises in troponins and creatinine kinase MB, although
      this has not been found by all authors. Some of this controversy may at least in
      part be due to the collection of blood samples immediately postdialysis, which is
      likely to be too early to reliably detect dialysis-induced elevations of cardiac
      enzymes. Cardiovascular death is the biggest single cause of mortality in
      dialysis patients and of this sudden death comprises the largest proportion. As
      such, there is a large body of evidence examining whether dialysis is pro
      arrhythmogenic. It is clear that dialysis can increase QTc interval and QT
      dispersion and is capable of inducing arrhythmias on Holter monitoring, likely
      due to the interaction of multiple factors, some of which prime for the
      development of arrhythmias (particularly the presence of preexisting cardiac
      disease), and some of which act as triggers. However, the link between these
      electrocardiographic alterations and sudden death is relatively poorly studied.
      This review summarizes the available literature regarding the acute cardiac
      effects of dialysis in relation to the above, and discusses how these acute
      changes may contribute to the genesis of uremic cardiomyopathy and longer term
      cardiac outcomes.

PMID- 17555489
TI  - Familial clustering of chronic kidney disease.
AB  - The incidence and prevalence rates of most forms of chronic kidney disease (CKD)
      had steadily been increasing for the past 30 years, although these rates now
      appear to have reached a plateau. It is clear that an individual's likelihood of
      developing progressive CKD results from complex interactions between multiple
      genetic and environmental factors. Familial clustering of CKD and end-stage renal
      disease (ESRD) is observed among all the common etiologies of nephropathy. This
      article reviews the epidemiology of the familial clustering of kidney disease, as
      well as potential environmental and genetic contributors. The related impact of
      familial clustering of cardiovascular disease (CVD) and the impact of CVD on the
      current epidemic of ESRD is also discussed. It is imperative that nephrologists
      and primary care physicians recognize that individuals who have relatives with
      advanced nephropathy are themselves at high risk for subsequent kidney disease,
      proteinuria, and atherosclerotic cardiovascular complications. Until kidney
      failure genes are identified, it is reasonable to use "family history" (FH) as a
      surrogate marker for risk of future nephropathy. The detection of kidney disease
      genes holds great promise for detecting novel pathways that initiate renal
      fibrosis and lead to progressive loss of renal function. These pathways are
      likely to offer new therapies that may slow or halt development of chronic kidney
      failure.

PMID- 17555490
TI  - Fluid mechanics and clinical success of central venous catheters for dialysis-
      answers to simple but persisting problems.
AB  - Over 60% of patients initiating chronic hemodialysis in the United States have a
      chronic central venous catheter (CVC) as their first blood access device.
      Although it would be better if these patients started dialysis with fistulas, the
      CVC is used because it is a reliable and relatively safe method for obtaining
      blood access over a period of months. Drawing blood from a vein at 300-400
      ml/minute is a relatively delicate and somewhat unpredictable process, and there
      is always a tendency for the vein wall to draw over the arterial tip and obstruct
      flow. Several methods have been employed to minimize this problem and maximize
      blood flow, and differing catheter designs have resulted. With all of the
      different catheter designs now on the market, it is natural to ask what is the
      logic of different designs. Moreover, in the absence of many direct comparative
      studies it is natural to ask whether one design is really better than another.
      There is some misinformation regarding catheter design and function. The
      following is a list of 10 frequently asked questions In this review, the
      hydraulic features of CVC are discussed and explained, and logical answers are
      provided for the following questions: 1. Why do ''D'' catheters flow better than
      concentric or side by side catheters? 2. Why are all catheters about the same
      diameter? Does making them bigger really decrease the resistance to flow? 3. Why
      might a split tip catheter flow better than a solid body catheter? 4. What
      happens to injections of lock solution at catheter volume? 5. What's better
      numerous side holes or none? 6. Why does blood rise into some internal jugular
      catheters over time, displacing the lock solution? 7. How can a little kink (or
      stenosis) decrease flow so much? 8. Where should the tips be placed-superior vena
      cava or right atrium? 9. Which is really better, splitsheath or over-the-wire
      placement? 10. Which dialysis access has a lower complication rate--CVC or
      arteriovenous (AV) graft? There remain important problems with CVC for dialysis.
      With a few more improvements, chronic CVC for dialysis could become a painless,
      effective and safe long-term access for the majority of dialysis patients and
      acceptable as an alternative to AV grafts.

PMID- 17555491
TI  - Medical direction of dialysis--a critical leadership role.
AB  - The position of medical director of a dialysis unit is important, requires
      leadership, knowledge, interest, energy, and commitment. The position is mandated
      by the federal regulations and is necessary to quality and performance of the
      unit.

PMID- 17555492
TI  - The dialysis medical director's role in quality and safety.
AB  - The medical director of dialysis is responsible for leadership in a dialysis
      facility's quality improvement activities and patient safety initiatives. The
      Director should have knowledge of, and an ability to utilize, Continuous Quality
      Improvement techniques, evidence-based guidelines, standardized mortality,
      hospitalization and transplantation data and other modalities to improve systems
      of care.

PMID- 17555493
TI  - Effects of home hemodialysis on health-related quality of life measures.
AB  - In recent years, there has been an increased interest in performing hemodialysis
      (HD) more frequently than thrice weekly, particularly in the home setting. This
      interest has been stimulated by some studies that have indicated significant
      benefits to performing more frequent HD on various medical and quality of life
      outcome measures. However, only a few studies using varying quality of life
      instruments have critically examined the impact of frequent HD on the quality of
      life of patients. Although not consistent across studies, results suggest a
      positive impact of more frequent HD on patients' quality of life. It is hoped
      that the results of two landmark studies, now in progress (the Frequent
      Hemodialysis Network trial and the FREEDOM study), will provide more insight into
      the impact of more frequent HD on quality of life.

PMID- 17555494
TI  - Facial and left arm swelling in a hemodialysis patient.

PMID- 17555495
TI  - Nontuberculous mycobacterial peritonitis in peritoneal dialysis patients.
AB  - While nontuberculous mycobacterial peritonitis is uncommon among peritoneal
      dialysis (PD) patients, these infections have serious consequences. They present
      a significant diagnostic and therapeutic challenge for clinicians. Diagnosis can
      be delayed due to the slow growth rate of some mycobacterial species. These
      organisms can also be overlooked when adequate culture media are not used in the
      microbiological evaluation process. The choice of antimicrobial therapy depends
      upon isolation and speciation of the infecting Mycobacterium species, and prompt
      catheter removal is essential. Because serious intra-abdominal complications may
      follow infection, identifying patient risk factors for nontuberculous
      mycobacterial peritonitis and initiating prompt diagnosis and treatment are
      essential. We report three cases of peritonitis associated with Mycobacterium
      chelonae and Mycobacterium gordonae, each with a unique presentation, and discuss
      the appropriate diagnosis and treatment strategies for the management of PD
      associated mycobacterial infections.

PMID- 17555496
TI  - CHOIR, CREATE, and anemia treatment in patients with CKD.

PMID- 17555498
TI  - Rosiglitazone decreases 11beta-hydroxysteroid dehydrogenase type 1 in
      subcutaneous adipose tissue.
AB  - OBJECTIVE: The peroxisome proliferator-activated receptor-gamma (PPARgamma)
      agonist rosiglitazone increases insulin sensitivity, which, in animal models, is
      comparable to the effect of a reduction in 11beta-hydroxysteroid dehydrogenase
      type 1 (11beta-HSD1) activity. We therefore investigated whether rosiglitazone
      induced insulin sensitivity is associated with changes in 11beta-HSD1 activity in
      different tissues. METHODS: An oral glucose tolerance test (OGTT) and a
      euglycaemic hyperinsulinaemic clamp were performed in seven male volunteers [age
      59.3 +/- 3.0 years, body mass index (BMI) 29.3 +/- 4.1 kg/m(2)] with impaired
      glucose tolerance before and after 8 weeks of rosiglitazone treatment. To assess
      hepatic 11beta-HSD1 activity, serum cortisol levels were measured after oral
      administration of cortisone acetate. 11beta-HSD1 activity and mRNA expression
      were assessed in abdominal subcutaneous fat biopsies. Total-body 11beta-HSD
      activities were estimated by calculating the urinary ratios of glucocorticoid
      metabolites. RESULTS: As expected, rosiglitazone improved insulin resistance and
      postprandial hyperglycaemia. In parallel, 11beta-HSD1 mRNA expression [100 +/- 0%
      (reference) vs. 68.5 +/- 9.3%, P < 0.01] and activity [0.18 +/- 0.02 vs. 0.13 +/-
      0.02 pmol/min/mg, P < 0.05] decreased in abdominal subcutaneous fat, while an
      increase in hepatic 11beta-HSD1 activity was detected [the area under the curve
      (AUC) for the cortisol/cortisone ratio was 1319 +/- 76 vs. 955 +/- 59; P < 0.05].
      No changes in BMI, waist-to-hip ratio (WHR) and whole-body 11beta-HSD1 activity
      were found. CONCLUSIONS: Part of the beneficial effects of rosiglitazone may be
      mediated by a reduction in the 11beta-HSD1 mRNA expression and activity in
      subcutaneous abdominal fat.

PMID- 17555499
TI  - Novel MEN1 germline mutations in Brazilian families with multiple endocrine
      neoplasia type 1.
AB  - OBJECTIVE: To characterize clinical features and identify MEN1 germline mutations
      in Brazilian families with multiple endocrine neoplasia type 1 (MEN1). Settings
      Non-profit academic centre. PATIENTS: Fourteen Brazilian families with MEN1 and
      141 at-risk relatives. RESULTS: We identified 12 different MEN1 disease-causing
      mutations, seven of them previously unreported: 308delC; 375del21; 549A>T
      (I147F); 1243delA; 1348T>G (L413R); 1351T>C (L414P) and 1523G>T (W471C). Families
      with the recurrent mutations 360delTCTA and L413R were shown to be unrelated by
      mitochondrial-DNA and Y-chromosome haplotype analyses. Most of the MEN1 single
      point mutations involved evolutionarily conserved residues, whereas most of the
      deletion/frameshift changes occurred in GC-rich repetitive regions. Genetic
      screening of 141 at-risk family members identified 38 MEN1 mutation carriers, 37
      (97.4%) of whom had at least one major MEN1-related tumour upon clinical
      investigation. CONCLUSIONS: High frequencies of MEN1 gene mutations were detected
      in Brazilian families with MEN1, including seven new genetic mutations that are
      predicted to cause inactivation of the MEN1 tumour suppressor gene. Our data
      underscore the need to implement a systematic MEN1 screening programme in Brazil.

PMID- 17555500
TI  - Identification of MEN1 and HRPT2 somatic mutations in paraffin-embedded
      (sporadic) parathyroid carcinomas.
AB  - OBJECTIVE: Parathyroid carcinoma remains difficult to diagnose. Recently, it has
      been shown that mutations in the HRPT2 gene (encoding parafibromin) are
      associated with the development of parathyroid carcinoma. Although MEN1 is not
      typically thought to be involved in carcinoma formation, parathyroid carcinoma
      may be an extremely rare feature of the multiple endocrine neoplasia type 1
      (MEN1) syndrome. We recently concluded that loss of heterozygosity (LOH) of the
      MEN1 gene is present in a relatively large number of parathyroid carcinomas,
      often in combination with LOH at the HRPT2 locus. The aim of this study was to
      evaluate the role of MEN1 and HRPT2 mutations in sporadic parathyroid tumours
      fulfilling histological criteria for malignancy. PATIENTS AND DESIGN: Formalin
      fixed, paraffin-embedded (FFPE) parathyroid carcinoma tissue from 28 cases
      identified in the period 1985-2000 in the Netherlands was studied. HRPT2 (27/28
      cases) and MEN1 (23/28 cases) were analysed by direct sequencing. RESULTS:
      Somatic MEN1 mutations were found in three of 23 (13%) sporadic parathyroid
      carcinoma cases; these consisted of one missense and two frameshift mutations.
      One of the latter two cases displayed lymph-node and lung metastases during
      follow-up. Six HRPT2 mutations were found in 4/27 cases (15%): five were
      truncating mutations and one was a missense mutation. Consistent with previously
      published reports, we found double mutations (2x) and germline mutations (2x) in
      apparently sporadic parathyroid carcinomas. CONCLUSIONS: These results suggest
      that not only HRPT2 but also MEN1 mutations may play a role in sporadic
      parathyroid cancer formation.

PMID- 17555501
TI  - Clinical features of thyroid autoimmunity are associated with thyroiditis on
      histology and are not predictive of malignancy in 570 patients with indeterminate
      nodules on cytology who had a thyroidectomy.
AB  - BACKGROUND: The relationship between thyroid autoimmunity and cancer is still
      uncertain. PATIENTS: We approached this issue in 570 consecutive patients
      submitted to thyroidectomy for an indeterminate nodule on cytology. Thyroid
      autoimmunity was defined as positivity of circulating thyroid autoantibodies
      (TAb), autoimmune hypo- or hyperthyroidism, thyroid hypoechogenicity on
      ultrasound, and lymphocytic infiltration on histology. RESULTS: TAb were found in
      122/570 (21.4%), hypoechogenicity in 115/570 (20.1%), and lymphocytic
      infiltration in 117/570 (20.5%) of patients. The three features of thyroid
      autoimmunity were highly concordant: hypoechogenicity was observed in 71/448
      (15.8%) patients with negative TAb and in 44/122 (36%) with positive TAb (P <
      0.0001); lymphocytic infiltration was found in 53/448 (11.8%) patients with
      negative TAb and in 64/122 (52.4%) with positive TAb (P < 0.0001);
      hypoechogenicity on ultrasound was observed in 73/453 (16.1%) patients without,
      and in 42/117 (35.9%) with lymphocytic infiltration (P < 0.0001). None of these
      parameters was associated with malignancy. TAb were found in 32/135 (23.7%)
      patients with carcinoma and in 90/435 (20.6%) with a benign lesion (P = NS);
      hypoechogenicity was observed in 26/135 (19.2%) patients with carcinoma and in
      89/435 (20.4%) patients with benign lesions (P = NS); lymphocytic infiltration
      was present in 28/135 (20.7%) patients with carcinoma and in 89/435 (20.4%) with
      benign lesions (P = NS). The frequency of cancer in 11 patients with clinically
      overt thyroid autoimmune disease did not differ from that observed in the whole
      study group. CONCLUSION: In this group of patients with indeterminate thyroid
      nodules at cytology, clinical and pathological criteria of thyroid autoimmunity
      were strongly concordant and not associated with malignancy.

PMID- 17555502
TI  - Treatment of acromegaly improves quality of life, measured by AcroQol.
AB  - BACKGROUND: AcroQol is a disease-generated questionnaire, developed to assess
      quality of life (QOL) in patients with acromegaly. We have previously
      demonstrated severely impaired QOL in patients with acromegaly and the value of
      AcroQol in measuring QOL in a cross-sectional study compared with the non-disease
      specific generic tools 'Psychological general wellbeing schedule' (PGWBS) and
      EuroQol (EQ-5D), and the disease-specific signs and symptoms score (SSS). AIM,
      SUBJECTS AND METHODS: We re-evaluated these tools in a longitudinal study of 56
      of the previously reported patients (33 male, mean age 55 +/- 15 years), in order
      to determine change in QOL over time and the effect of different treatment
      modalities. Data were analysed using Spearman's correlation tests. RESULTS:
      Baseline median IGF-I was 354 ng/ml (range 48-899) and at re-evaluation 217 ng/ml
      (60-594) (P < 0.001) [median time interval 608 days (113-1136)]. Analysis of
      change in IGF-I levels and AcroQol scores demonstrated a significant negative
      correlation (i.e. a reduction in IGF-I being associated with improved overall QOL
      (r = -0.36, P = 0.006). Significant negative correlations were also seen in the
      physical (r = -0.33, P = 0.01), psychological (r = -0.37, P = 0.005) and
      appearance (r = -0.42, P = 0.001) AcroQol subdomains. No correlations were seen
      between change in IGF-I and change in overall PGWBS score or subdomains, SSS or
      EQ-5D. CONCLUSIONS: In summary, of the tools studied we have demonstrated AcroQol
      to be uniquely capable of detecting changes in QOL associated with treatment
      induced improvement in the main biochemical marker of disease activity in
      patients with acromegaly. Further studies are required to evaluate the long-term
      biological significance of the changes seen in AcroQol.

PMID- 17555503
TI  - Does partial surgical tumour removal influence the response to octreotide-LAR in
      acromegalic patients previously resistant to the somatostatin analogue?
AB  - OBJECTIVE: To compare the intrapatient response to the same dose of slow-release
      octreotide (OCT-LAR) before and after noncurative surgery in acromegalic patients
      who did not attain disease control after primary treatment with OCT-LAR. DESIGN:
      Prospective clinical study. PATIENTS: Eleven acromegalic patients (eight men,
      aged 42.45 +/- 11.15 years, 10 macroadenomas) received OCT-LAR (20 mg, n = 1; 30
      mg, n = 10) every 28 days as the primary treatment (1stOCT-LAR) for 11.3 +/- 4.2
      months, without IGF-I normalization. They were subsequently submitted to surgery
      without cure and were then treated with the same dose of OCT-LAR for 8.0 +/- 6.5
      months (2ndOCT-LAR). MEASUREMENTS: GH and IGF-I serum concentrations were
      obtained under basal conditions as well as during treatment. Pituitary tumour
      volume was assessed by magnetic resonance imaging (MRI) of the sella. IGF-I was
      also expressed as a percentage of the upper limit of the normal age- and sex
      matched range (%ULNR IGF-I). RESULTS: After 1stOCT-LAR, there was a decrease in
      GH levels (P = 0.003) and %ULNR IGF-I (P = 0.009) compared to baseline (B), but
      no IGF-I normalization. Tumour shrinkage was observed in eight of 10 patients
      with macroadenomas (median 63.7%, range 24.5-75.5%). After surgery, mean levels
      of GH and %ULNR IGF-I were lower than those at baseline (P = 0.0004 and P =
      0.003, respectively), but not when compared to values during 1stOCT-LAR (P =
      1.000 and P = 0.957, respectively). MRI confirmed surgical tumour removal (median
      64%, range 4.9-96.6%) in eight of the 10 patients. Comparing the 2ndOCT-LAR
      results with postsurgical results, there were no significant decrease in %ULNR
      IGF-I (P = 0.061) and GH levels (P = 0.414). Nine patients (82%) achieved IGF-I
      normalization. The degree of surgical tumour reduction did not correlate with IGF
      I normalization (P = 0.794). When comparing the results between 1stOCT-LAR and
      2ndOCT-LAR, there was a decrease, albeit not statistically significant, in serum
      GH levels (P = 0.059) and a significant decrease in %ULNR IGF-I (P = 0.011).
      CONCLUSIONS: Using strict criteria (same patient, same drug, same dose) our
      results strongly suggest that the surgical reduction of tumour mass can improve
      the outcome of OCT-LAR treatment in acromegalic patients resistant to primary
      therapy with SA.

PMID- 17555504
TI  - The association of sex hormone levels with quantitative ultrasound, bone mineral
      density, bone turnover and osteoporotic fractures in older men and women.
AB  - OBJECTIVE: Sex steroids play an important role in the maintenance of bone health.
      Association studies on sex steroids and fractures are not consistent. Our
      objective was to examine whether serum oestradiol (E2) and testosterone (T) are
      associated with quantitative ultrasound (QUS), bone mineral density (BMD), bone
      turnover markers and fracture incidence. DESIGN: The Longitudinal Ageing Study
      Amsterdam (LASA), an ongoing cohort study including 623 men and 634 women, aged
      65-88 years. MEASUREMENTS: Serum levels of E2, T, SHBG, albumin, bone turnover
      markers serum osteocalcin (OC) and urinary deoxypyridinoline (DPD/Cr) were
      measured. QUS of the heel and BMD of the hip were assessed, and a 6-year fracture
      follow-up was performed. RESULTS: Men in the lowest quartile (Q1) of bioavailable
      E2 (bioE2) had higher levels of bone turnover and lower BMD (B = -0.09, P < 0.01)
      and QUS than men in the highest quartile (Q4). This also applied to Q1 of bioT.
      Women in Q1 of bioE2 had higher levels of bone turnover and lower BMD (B = -0.07,
      P < 0.01) and QUS than women in Q4. In men and women, levels of bioE2 below the
      median were associated with an increased risk of osteoporotic fractures after all
      adjustments [hazard ratio (HR) 1.53, 95% confidence interval (CI) 1.02-2.29]. In
      men, univariate analysis revealed that low bioT was associated with an increased
      fracture risk (HR 1.91, 95% CI 1.03-3.56), but after adjustment for age, this
      association was no longer significant. CONCLUSIONS: Low levels of bioE2 and bioT
      were found to be associated with high bone turnover, low QUS and BMD and high
      risk of osteoporotic fractures in both men and women.

PMID- 17555505
TI  - Clinical relevance of highly sensitive Tg assay in monitoring patients treated
      for differentiated thyroid cancer.
AB  - OBJECTIVE: Serum thyroglobulin (Tg) represents a highly specific biomarker for
      detecting residual thyroid tissue/recurrence/metastases after treatment for
      differentiated thyroid cancer (DTC). We evaluated the clinical impact of a highly
      sensitive Tg assay during routine follow-up of DTC patients. DESIGN: Tg values
      were measured by a highly sensitive Tg assay during L-T4 suppressive therapy and
      after recombinant human thyrotropin (rh-TSH) stimulation and were compared with
      those obtained by using a routinely employed Tg assay. PATIENTS: One hundred and
      sixty consecutive DTC-treated patients (papillary carcinoma n = 124, follicular
      carcinoma n = 36) were studied. MEASUREMENTS: Measured variables included neck
      ultrasonography, (131)I whole body scanning, and Tg assayed by Immulite
      (Diagnostic Products Corporation, Los Angeles, CA) and by the highly sensitive
      Access assay (Beckman Coulter, Brea, CA). RESULTS: During L-T4 therapy,
      measurable Tg was found in only two patients (1% of total) by Immulite and in 23
      patients (14% of total) by Access assay. Using the institutional cut-off of 2
      microg/l after rh-TSH, a negative response was associated with undetectable
      Immulite Tg during L-T4 therapy in all patients (negative predictive value, NPV,
      100%) and in 137 out of 152 patients with Access assay (NPV 90%). Measurable Tg
      during L-T4 therapy was found in 17% of positive patients with Immulite and in
      100% of patients with Access, respectively. CONCLUSIONS: The use of a highly
      sensitive Tg assay may represent a useful diagnostic tool for improving the
      interpretation of Tg results during monitoring of DTC-treated patients for the
      early detection of recurrence and for optimizing the use of the more expensive rh
      TSH test.

PMID- 17555506
TI  - Will highly sensitive thyroglobulin assays change the management of thyroid
      cancer?

PMID- 17555507
TI  - GH responsiveness in a large multinational cohort of SGA children with short
      stature (NESTEGG) is related to the exon 3 GHR polymorphism.
AB  - OBJECTIVE: The polymorphic deletion of exon 3 of the GH receptor (d3-GHR) has
      recently been linked to the magnitude of growth response to recombinant human GH
      (rhGH) therapy in short children with or without GH deficiency. We investigated
      this association in a large multinational cohort from the Network of European
      Studies of Genes in Growth (NESTEGG), comprising short children born small for
      gestational age (SGA). DESIGN: The study included short prepubertal SGA children
      treated with rhGH for 1 or 2 years. POPULATION: Two hundred and forty white
      Caucasian SGA children (138 male, 102 female) aged 6.6 +/- 2.3 years with a
      height at -3.0 +/- 0.7 SDS at start of rhGH treatment; 193 ethnically matched
      controls. METHODS: The GHR polymorphism (fl/fl, fl/d3 or d3/d3) was genotyped by
      polymerase chain reaction (PCR) multiplex assay. Growth velocity (G/V) in cm/year
      and changes in GV during the first and second year of rhGH treatment were
      evaluated. RESULTS: The change in GV was significantly greater in SGA children
      carrying one or two copies of the d3-GHR allele (P = 0.038 for the first year and
      P = 0.041 for the second year of GH treatment), but the change in height was not
      significantly different. Birthweight was significantly lower in SGA children with
      the d3/d3 genotype than in SGA children with the fl/fl genotype (P = 0.034) and
      in those with the fl/d3 genotype (P = 0.016). CONCLUSION: Our data, based on a
      large cohort, showed that the exon 3 GHR polymorphism is associated with
      responsiveness to rhGH treatment in SGA children with short stature.

PMID- 17555508
TI  - Neonatal severe hyperparathyroidism associated with a novel de novo heterozygous
      R551K inactivating mutation and a heterozygous A986S polymorphism of the calcium
      sensing receptor gene.
AB  - INTRODUCTION: Neonatal severe hyperparathyroidism (NSHPT) is induced by
      inactivating mutations of human calcium-sensing receptor (CaSR). Only three
      heterozygous de novo inactivating mutations of CaSR causing NSHPT have been
      described. We report the case of a now 11-year-old boy with NSHPT and we
      characterize a novel inactivating mutation along with the results of some
      functional analyses. PATIENT AND METHODS: As a neonate the patient presented the
      clinical syndrome of NSHPT. At 6 years of age persisting hypercalcaemia without
      clinical symptoms was documented, and the patient remained completely symptom
      free without parathyroid surgery until his present age of 11 years. The entire
      coding region of the CaSR gene of the patient and his family members was
      sequenced. Functional investigation was performed in HEK-293 cells, transiently
      transfected with wild type and mutant CaSR plasmid constructs. RESULTS: Sequence
      analysis revealed a novel de novo heterozygous mutation at codon 551 (AGG-->AAG),
      predicting a change of arginine to lysine (R551K) and a known heterozygous
      polymorphism (A986S) on the same allele, which was inherited from the father. We
      demonstrated that the novel R551K mutation significantly reduced the calcium
      sensitivity of CaSR (EC50: from 3.38 +/- 0.62-6.10 +/- 0.83 mmol/l), which was
      not alleviated by the simultaneous presence of A986S polymorphism. CONCLUSIONS:
      We present the fourth NSHPT case induced by a novel de novo heterozygous
      inactivating mutation (R551K) of the CaSR gene. The disease gradually reverted to
      a symptomless, benign condition resembling familial hypocalciuric hypercalcaemia
      without any surgical intervention.

PMID- 17555509
TI  - Cortisol-cortisone ratios in small for gestational age (SGA) children without
      postnatal catch-up growth.
AB  - OBJECTIVE: Low birthweight is a risk factor for metabolic and cardiovascular
      disorders in later adult life. Changes in the activity of 11beta-hydroxysteroid
      dehydrogenase type 2 (11beta-HSD2) and the consequent disequilibrium between
      cortisol (F) and cortisone (E) are thought to be a key mechanism for these
      effects. We investigated whether prenatal programming leads to alterations in F/E
      ratios on a systemic level. DESIGN, PATIENTS AND METHODS: In a cross-sectional,
      retrospective study we analysed sera of 132 children born small for gestational
      age (SGA) (aged 2-13 years) with persistent short stature [< -2 standard
      deviation score (SDS)] and of 25 children born appropriate for gestational age
      (AGA) (aged 4-11 years) with normal body height. Thirty-one per cent of the SGA
      and 44% of the AGA children were born preterm. Serum E and F concentrations were
      measured using tandem mass spectrometry. To exclude species-specific effects, we
      studied the 11beta-HSD system by measuring the ratio of corticosterone (B) to
      dehydrocorticosterone (11OH-B) in rats that were born SGA after protein
      restriction of the female dams during pregnancy. RESULTS: F, E and the F/E ratio
      in serum did not differ in these children when comparing SGA to children who were
      born AGA and had normal height. The concentrations were independent of weight and
      length SDS at birth as well as gestational age. In rats born SGA, the B/11OH-B
      ratio was not different to that in normal control animals at 6, 11 and 15 weeks
      of life. CONCLUSION: We found no alterations in systemic cortisol-cortisone
      conversion either in short children born SGA or in SGA rats. However, local
      modifications of the 11beta-HSD system may be possible.

PMID- 17555510
TI  - Autoimmune thyroid disease and chronic urticaria.
AB  - We report six cases of autoimmune thyroid disease associated with chronic
      urticaria and briefly review the literature, including the histopathological
      nature of such lesions, and their aetiology and pathogenesis. In view of the
      prevalence of thyroid disease in patients with chronic urticaria, screening
      measurements of thyrotropin and anti-thyroperoxidase antibodies are recommended,
      although negative antibodies do not exclude a relationship between urticaria and
      thyroid autoimmunity. After failure of conventional therapy for urticaria,
      patients who are apparently clinically euthyroid may be considered for a trial
      with levothyroxine. Improvement of urticaria was seen with levothyroxine
      treatment in three of four patients with only marginal abnormalities in thyroid
      function.

PMID- 17555511
TI  - Efficacy of a slow-release formulation of lanreotide (Autogel) 120 mg) in
      patients with acromegaly previously treated with octreotide long acting release
      (LAR): an open, multicentre longitudinal study.
AB  - OBJECTIVE: Lanreotide Autogel 120 mg (ATG120; Ipsen S.p.A, Milan, Italy) is a
      high-dose, sustained-release aqueous gel formulation, supplied in a prefilled
      syringe and given by deep subcutaneous injection. The aim of this study was to
      compare efficacy and tolerability of ATG120 given every 4-8 weeks with those of
      octreotide LAR (o-LAR) given every 4 weeks. DESIGN PATIENTS AND INTERVENTION: A
      phase III multicentre Italian open clinical study of 23 acromegalic patients (15
      female, 8 male). All patients had received o-LAR for 6-18 months and, after 3
      months wash out, ATG120 was given every 6 weeks for a total of four injections
      (Period 1). Then the interval between ATG120 injections was adjusted according to
      three different schemes: every 4, 6 or 8 weeks depending on GH levels (GH > 2.5
      microg/l; 1 < GH <or= 2.5 microg/l; GH <or= 1 microg/l, respectively). ATG120 was
      given for a further two to three doses, with a final assessment (Period 2) at
      Week 34, 36 or 42. MEASUREMENTS: Hormonal (GH and IGF-I) and clinical efficacy
      and tolerability. RESULTS: ATG120 induced a significant GH decrease from 9.9 +/-
      11.3 at baseline (Visit 1) to 3.5 +/- 5.7 at the end of Period 1 (P < 0.01) and
      to 3.8 +/- 5.7 microg/l at the final visit (P < 0.01). IGF-I also decreased from
      544 +/- 312 at baseline (Visit 1) to 318 +/- 181 at Period 1 and to 356 +/- 187
      microg/l at the final visit (both P < 0.05 vs. baseline). The frequency of ATG120
      administrations was adjusted to every 4 weeks in 12 patients, every 6 weeks in 4
      patients and every 8 weeks in 6 patients; 1 patient withdrew before the dose
      adjustment. Serum GH and IGF-I achieved at the end of Period 1 and Period 2 were
      similar to those reached with o-LAR. The number of patients who achieved GH < 2.5
      microg/l was comparable between o-LAR (43%) and ATG120 at Period 1 (48%) and at
      Period 2 (62%). Normal IGF-I levels were recorded in 8 patients during o-LAR
      (35%), 11 during ATG Period 1 (48%) and 10 at the final visit (43%). Last, 4
      patients showed a better response to ATG120 and 2 to o-LAR. CONCLUSIONS:
      Lanreotide Autogel 120 mg is an effective and well-tolerated therapy for
      acromegaly. In approximately half of patients ATG120 may be administered every 6
      8 weeks, instead of every 4 weeks, without lost of efficacy.

PMID- 17555512
TI  - Exon 3-deleted genotype of growth hormone receptor (GHRd3) positively influences
      IGF-1 increase at generation test in children with idiopathic short stature.
AB  - CONTEXT: A GHR-exon 3 polymorphism has been reported to influence the growth
      response to hGH therapy in short stature children. None of these studies provided
      data on IGF-1 generation test. OBJECTIVE: To evaluate the influence of the GHR
      exon 3 polymorphism on the generation test in children with idiopathic short
      stature (ISS). DESIGN AND PATIENTS: A total of 45 prepubertal ISS children were
      submitted to IGF-1 and IGFBP-3 generation test (4 days of hGH 33 microg/kg/day).
      Children were genotyped for GHR-exon 3: full-length (fl) and exon 3-deleted (d3)
      alleles. MEASUREMENTS: IGF-1 and IGFBP-3 increment as absolute values and
      standard deviation scores (SDS). RESULTS: Basal clinical and laboratory data were
      similar among patients with different genotypes (fl/fl vs. fl/d3 or d3/d3). All
      patients presented IGF-1 increase >or= 15 microg/l at generation test. Children
      with GHRd3 allele, as a group, presented a statistically significant higher IGF-1
      SDS increase at generation test than children homozygous for GHRfl allele (1.0
      ranging from 0.1 to 3.7 for fl/fl vs. 1.2 ranging from 0.3 to 4.4 for fl/d3 and
      d3/d3; P = 0.037). Multiple linear regression found a positive association
      between increase in IGF-1 SDS with chronological age (P = 0.007) and GHR genotype
      (P = 0.027), which together explain 24% of the variability of IGF-1 SDS increment
      at generation test. There was no difference in IGFBP-3 generation test between
      the two genotype groups. CONCLUSION: This study demonstrates that ISS children
      carrying the GHRd3 allele, as a group, present a slightly higher GH sensitivity
      regarding short-term IGF-1 generation during hGH stimulus than children
      homozygous for GHRfl allele.

PMID- 17555513
TI  - Insulin resistance after precocious pubarche: relation to PAI-1-675 4G/5G
      polymorphism, and opposing influences of prenatal and postnatal weight gain.
AB  - OBJECTIVE: The common promoter -675 4G/5G insertion/deletion polymorphism (indel)
      in the plasminogen activator inhibitor-1 (PAI-1) gene has been associated with
      quantitative components of the metabolic syndrome. We hypothesized that this
      polymorphism is associated with precocious pubarche (PP), a population known to
      be at risk for hyperinsulinaemic hyperandrogenism. DESIGN: A cross-sectional,
      hospital-based study. PATIENTS: A total of 115 control and 182 PP Catalan girls
      and young women. MEASUREMENTS: Subjects were genotyped for the -675 4G/5G indel
      in the PAI-1 gene. Insulin resistance and insulin secretion were estimated by the
      homeostasis model assessment. RESULTS: Genotype frequencies for the PAI-1-675
      4G/5G indel (4G4G, 4G5G and 5G5G) were similar in control and PP subjects (24%vs.
      27%, 50%vs. 47%, and 26%vs. 26%, respectively; P = 0.85) and these frequencies
      were in Hardy-Weinberg equilibrium. The 5G allele, however, was associated with
      insulin resistance in both postmenarcheal control and PP subjects (P < 0.01 for
      pooled postmenarcheal subjects, N = 122). The coexistence with the at-risk
      genotype of both a low birthweight (standard deviation score, SDS < -1.0) and a
      high body mass index (BMI) at time of the study (SDS > +1.0) resulted in a
      noteworthy increase (P < 0.001) in insulin resistance. CONCLUSION: The common
      promoter -675 4G/5G indel of the PAI-1 gene is not associated with PP but, in
      Catalan young women, the 5G allele enhances the risk for insulin resistance
      imposed by the sequence of a low birth weight (LBW) and a high BMI.

PMID- 17555514
TI  - Cytokine profiling and in vitro studies of murine bone growth using biological
      fluids from children with juvenile idiopathic arthritis.
AB  - OBJECTIVE: Growth retardation in children with chronic inflammatory disease may
      be partly due to direct effects of pro-inflammatory cytokines on the growth plate
      and requires further investigation. DESIGN: This study assessed the cytokine
      concentrations in serum and synovial fluid (SF) in juvenile idiopathic arthritis
      (JIA), and determined the effect of the biological fluid on cultured murine
      metatarsal growth. PATIENTS: Serum and SF were obtained from four children
      attending for arthrocentesis (child A, systemic; children B, C and D,
      oligoarticular). In addition, serum samples were obtained from four more children
      (children E and F, polyarticular; child G, oligoarticular). MEASUREMENTS:
      Anthropometry, cytokine levels and longitudinal bone growth were assessed.
      RESULTS: Cytokines were elevated to a variable extent in the samples. Although
      all serum samples were associated with reduced metatarsal growth, only SF from
      child A and child B reduced metatarsal growth. Metatarsals treated with child A's
      SF showed reduced proliferation, reduced proliferative and mineralizing zone
      width, and increased hypertrophic zone width. Tumour necrosis factor (TNF)-alpha,
      interleukin (IL)-1beta and IL-6 concentrations were elevated in child A's SF.
      However, SF exposure with neutralizing antibodies to these cytokines or IGF-1 did
      not improve metatarsal growth. CONCLUSION: SF and serum JIA samples can impair
      bone growth at the growth plate. In synovial fluid, the effect is variable but
      resistant to treatment with IL-1beta, IL-6 and TNF-alpha specific antibodies and
      IGF-1, suggesting that other factors in this biological fluid may also have an
      effect on longitudinal growth through IGF-1-independent mechanisms.

PMID- 17555515
TI  - Relationship between cortisol and physical performance in older persons.
AB  - OBJECTIVE: Hypercortisolism is associated with muscle weakness. This study
      examines the relationship between cortisol and physical performance in older
      persons. DESIGN/PATIENTS: The study was conducted within the Longitudinal Aging
      Study Amsterdam (LASA), an ongoing cohort study in a population-based sample of
      healthy older persons in the Netherlands. Data from the second (1995/1996) and
      fourth (2001/2002) cycle were used pertaining to 1172 (65-88 years) and 884 (65
      94 years) men and women, respectively. MEASUREMENTS: Physical performance was
      measured by adding up scores on the chair stands, tandem stand and walk test
      (range 0-12). In the second cycle serum total and calculated free cortisol were
      assessed; in the fourth cycle evening salivary cortisol was assessed. Regression
      analysis (stratified for sex, adjusted for age, body mass index, alcohol use,
      physical activity and region) was performed to examine the cross-sectional
      relationship between cortisol and physical performance. RESULTS: Women with
      higher calculated free cortisol scored less well on physical performance (b = 
      0.28 per SD higher cortisol, P = 0.016), which was mainly explained by poorer
      performance on the tandem stand (OR = 1.32 for a lower score per SD higher
      cortisol, P = 0.003). Men with higher salivary cortisol scored less well on
      physical performance (b = -0.90 in the highest vs. the lowest quartile, P =
      0.008), which was mainly explained by poorer performance on the chair stands and
      walk test (OR = 1.88, P = 0.020 and OR = 1.81, P = 0.027, respectively, in the
      highest vs. the lowest quartile). CONCLUSION: Physical performance is negatively
      associated with high cortisol levels in older persons.

PMID- 17555516
TI  - Type II phosphatidylinositol 4-kinases promote Listeria monocytogenes entry into
      target cells.
AB  - Interaction of the Listeria surface protein InlB with the hepatocyte growth
      factor receptor Met activates signalling events that trigger bacterial
      internalization into mammalian epithelial cells. We show here that purified
      phagosomes containing InlB-coated beads display type II phosphatidylinositol 4
      kinase (PI4K) activity. In human epithelial HeLa cells, both PI4KIIalpha and
      PI4KIIbeta isoforms are corecruited with Met around InlB-coated beads or wild
      type Listeria during the early steps of internalization, and phosphatidylinositol
      4-phosphate [PI(4)P] is detected at the entry site. We demonstrate that
      PI4KIIalpha or PI4KIIbeta knockdown, but not type III PI4Kbeta knockdown,
      inhibits Listeria internalization. Production of PI(4)P derivatives such as
      phosphatidylinositol 3,4,5-triphosphate [PI(3,4,5)P(3)] upon InlB stimulation is
      not affected by PI4KIIalpha or beta knockdown, suggesting that these
      phosphoinositides are generated by a type III PI4K. Strikingly, knockdown of the
      PI(4)P ligand and clathrin adaptor AP-1 strongly inhibits bacterial entry.
      Together, our results reveal a yet non-described role for type II PI4Ks in
      phagocytosis.

PMID- 17555517
TI  - Requirement for ErbB2/ErbB signaling in developing cartilage and bone.
AB  - During endochondral ossification, the skeletal elements of vertebrate limbs form
      and elongate via coordinated control of chondrocyte and osteoblast
      differentiation and proliferation. The role of signaling by the ErbB family of
      receptor tyrosine kinases, which consists of ErbB1 (epidermal growth factor
      receptor or EGFR), ErbB2, ErbB3 and ErbB4, has been little studied during
      cartilage and bone development. Signaling by the ErbB network generates a diverse
      array of cellular responses via formation of ErbB dimers activated by distinct
      ligands that produce distinct signal outputs. Herstatin is a soluble ErbB2
      receptor that acts in a dominant negative fashion to inhibit ErbB signaling by
      binding to endogenous ErbB receptors, preventing functional dimer formation.
      Here, we examine the effects of Herstatin on limb skeletal element development in
      transgenic mice, achieved via Prx1 promoter-driven expression in limb cartilage
      and bone. The limb skeletal elements of Prx1-Herstatin embryos are shortened, and
      chondrocyte maturation and osteoblast differentiation are delayed. In addition,
      proliferation by chondrocytes and periosteal cells of Prx1-Herstatin limb
      skeletal elements is markedly reduced. Our study identifies requirements for ErbB
      signaling in the maintenance of chondrocyte and osteoblast proliferation involved
      in the timely progression of chondrocyte maturation and periosteal osteoblast
      differentiation.

PMID- 17555518
TI  - Studies on the role of Dlx5 in regulation of chondrocyte differentiation during
      endochondral ossification in the developing mouse limb.
AB  - The homeodomain transcription factor Dlx5 has been implicated in the regulation
      of chondrocyte and osteoblast differentiation during endochondral ossification in
      the developing limb. In a gain-of-function approach to directly investigate the
      role of Dlx5 in chondrocyte maturation, we have used cartilage-specific Col2a1
      Dlx5 promoter/enhancer constructs to target overexpression of Dlx5 to the
      differentiating cartilage models of the limbs of transgenic mice. Targeted
      overexpression of Dlx5 in cartilage rudiments results in the formation of
      shortened skeletal elements containing excessive numbers of hypertrophic
      chondrocytes and expanded domains of expression of Ihh and type X collagen,
      molecular markers of hypertrophic maturation. This suggests that hypertrophic
      differentiation is enhanced in response to Dlx5 misexpression. Skeletal elements
      overexpressing Dlx5 also exhibit a marked reduction in the zone of proliferation,
      indicating that overexpression of Dlx5 reduces chondrocyte proliferation
      concomitant with promoting hypertrophic maturation. Taken together these results
      indicate that Dlx5 is a positive regulator of chondrocyte maturation during
      endochondral ossification, and suggest that it regulates the process at least in
      part by promoting the conversion of immature proliferating chondrocytes into
      hypertrophying chondrocytes; a critical step in the maturation process.

PMID- 17555519
TI  - Clinical features and teratogenic mechanisms of congenital absence of digits.
AB  - To have a better understanding of classification of congenital hand anomalies,
      clinical features and teratogenic mechanisms of congenital absence of digits
      including ulnar and radial deficiencies, cleft hand, symbrachydactyly and
      constriction band were reviewed. There seemed to be four different teratogenic
      mechanisms of congenital absence of digits. Ulnar and radial deficiencies have
      the same clinical features and the cause of these deficiencies is closely related
      to a deficit of mesenchymal cells in the limb-bud due to impairment before the
      formation of the limb-bud. Cleft hand, central polydactyly and osseous syndactyly
      were induced by the same treatment at the same developmental stage in rats.
      Roentgenograms of the clinical cases and skeletal changes of the anomalies in
      rats appear to demonstrate that cleft hand formation proceeds from osseous
      syndactylies and central polydactylies. The teratogenic mechanism of a cleft hand
      seemed to be failure of induction of digital rays in the hand plate. The sequence
      of anomalies from brachysyndactyly, or the atypical cleft hand, to the congenital
      amputation, can be regarded as equivalent to the category of transverse
      deficiency that is bony dysplasia of the hand. Congenital constriction ring
      syndrome appears after the formation of the digital rays.

PMID- 17555520
TI  - A vertebrate slow skeletal muscle actin isoform.
AB  - Salmonids utilize a unique, class II isoactin in slow skeletal muscle. This actin
      contains 12 replacements when compared with those from salmonid fast skeletal
      muscle, salmonid cardiac muscle and rabbit skeletal muscle. Substitutions are
      confined to subdomains 1 and 3, and most occur after residue 100. Depending on
      the pairing, the 'fast', 'cardiac' and rabbit actins share four, or fewer,
      substitutions. The two salmonid skeletal actins differ nonconservatively at six
      positions, residues 103, 155, 278, 281, 310 and 360, the latter involving a
      change in charge. The heterogeneity has altered the biochemical properties of the
      molecule. Slow skeletal muscle actin can be distinguished on the basis of mass,
      hydroxylamine cleavage and electrophoretic mobility at alkaline pH in the
      presence of 8 m urea. Further, compared with its counterpart in fast muscle, slow
      muscle actin displays lower activation of myosin in the presence of regulatory
      proteins, and weakened affinity for nucleotide. It is also less resistant to urea
      and heat-induced denaturation. The midpoints of the change in far-UV ellipticity
      of G-actin versus temperature are approximately 45 degrees C ('slow' actin) and
      approximately 56 degrees C ('fast' actin). Similar melting temperatures are
      observed when thermal unfolding is monitored in the aromatic region, and is
      suggestive of differential stability within subdomain 1. The changes in
      nucleotide affinity and stability correlate with substitutions at the nucleotide
      binding cleft (residue 155), and in the C-terminal region, two parts of actin
      which are allosterically coupled. Actin is concluded to be a source of skeletal
      muscle plasticity.

PMID- 17555521
TI  - Arabidopsis amidase 1, a member of the amidase signature family.
AB  - Amidase 1 (AMI1), a specific indole-3-acetamide amidohydrolase, is an Arabidopsis
      thaliana amidase signature enzyme that catalyzes the synthesis of indole-3-acetic
      acid from indole-3-acetamide. Amidase signature family members catalyze a diverse
      range of enzymatic reactions and are found widespread in nature, for instance in
      bacteria, mammals, and plants. At the protein level, the family members share a
      conserved stretch of approximately 50-130 amino acids, the name-giving amidase
      signature. Elucidation of the crystal structures of a mammalian fatty acid amide
      hydrolase and the bacterial malonamidase E2 revealed an unusual Ser-cisSer-Lys
      catalytic triad in proteins of this family. In addition, other members, such as
      the amidase from Rhodococcus rhodochrous strain J1 or Sulfolobus solfataricus,
      seem to use an accessory Cys-cisSer-Lys center. AMI1 possesses all conserved
      amino-acid residues of the Ser-cisSer-Lys triad, but lacks the CX(3)C motif and
      therefore the Cys-cisSer-Lys catalytic site. Using a set of point-mutated
      variants of AMI1 and chemical modifications, we analyzed the relative importance
      of single amino-acid residues of AMI1 with respect to substrate conversion. These
      experiments revealed that a specific serine residue, Ser137, is essential for
      AMI1 enzymatic activity. We also report structural and functional differences of
      AMI1 from other amidase signature enzymes.

PMID- 17555522
TI  - The Runx3 distal transcript encodes an additional transcriptional activation
      domain.
AB  - The runt family transcriptional regulator, Runx3, is upregulated during the
      differentiation of CD8 single-positive thymocytes and is expressed in peripheral
      CD8(+) T cells. Mice carrying targeted deletions in Runx3 have severe defects in
      the development and activation of CD8(+) T cells, resulting in decreased CD8(+) T
      cell numbers, aberrant coexpression of CD4, and failure to expand CD8(+) effector
      cells after activation in vivo or in vitro. Expression of each of the three
      vertebrate runt family members, including Runx3, is controlled by two promoters
      that generate proteins with alternative N-terminal sequences. The longer N
      terminal region of Runx3, expressed from the distal promoter, is highly conserved
      among family members and across species. We show that transcripts from the distal
      Runx3 promoter are selectively expressed in mature CD8(+) T cells and are
      upregulated upon activation. We show that the N-terminal region encoded by these
      transcripts carries an independent transcriptional activation domain. This domain
      can activate transcription in isolation, and contributes to the increased
      transcriptional activity observed with this isoform as compared to those
      expressed from the ancestral, proximal promoter. Together, these data suggest an
      important role for the additional N-terminal Runx3 activation domain in CD8(+) T
      cell function.

PMID- 17555523
TI  - An intermediate step in the evolution of ATPases--the F1F0-ATPase from
      Acetobacterium woodii contains F-type and V-type rotor subunits and is capable of
      ATP synthesis.
AB  - Previous preparations of the Na(+) F(1)F(0)-ATP synthase solubilized by Triton X
      100 lacked some of the membrane-embedded motor subunits [Reidlinger J & Muller V
      (1994) Eur J Biochem233, 275-283]. To improve the subunit recovery, we revised
      our purification protocol. The ATP synthase was solubilized with dodecylmaltoside
      and further purified to apparent homogeneity by chromatographic techniques. The
      preparation contained, along with the F(1) subunits, the entire membrane-embedded
      motor with the stator subunits a and b, and the heterooligomeric c ring, which
      contained the V(1)V(0)-like subunit c(1) and the F(1)F(0)-like subunits c(2) and
      c(3). After incorporation into liposomes, ATP synthesis could be driven by an
      electrochemical sodium ion potential or a potassium ion diffusion potential, but
      not by a sodium ion potential. This is the first demonstration that an ATPase
      with a V(0)-F(0) hybrid motor is capable of ATP synthesis.

PMID- 17555524
TI  - Isothermal unfolding studies on the apo and holo forms of Plasmodium falciparum
      acyl carrier protein. Role of the 4'-phosphopantetheine group in the stability of
      the holo form of Plasmodium falciparum acyl carrier protein.
AB  - The unfolding pathways of the two forms of Plasmodium falciparum acyl carrier
      protein, the apo and holo forms, were determined by guanidine hydrochloride
      induced denaturation. Both the apo form and the holo form displayed a reversible
      two-state unfolding mechanism. The analysis of isothermal denaturation data
      provides values for the conformational stability of the two proteins. Although
      both forms have the same amino acid sequence, and they have similar secondary
      structures, it was found that the - DeltaG of unfolding of the holo form was
      lower than that of the apo form at all the temperatures at which the experiments
      were done. The higher stability of the holo form can be attributed to the number
      of favorable contacts that the 4'-phosphopantetheine group makes with the surface
      residues by virtue of a number of hydrogen bonds. Furthermore, there are several
      hydrophobic interactions with 4'-phosphopantetheine that firmly maintain the
      structure of the holo form. We show here for the first time that the interactions
      between 4'-phosphopantetheine and the polypeptide backbone of acyl carrier
      protein stabilize the protein. As Plasmodium acyl carrier protein has a similar
      secondary structure to the other acyl carrier proteins and acyl carrier protein
      like domains, the detailed biophysical characterization of Plasmodium acyl
      carrier protein can serve as a prototype for the analysis of the conformational
      stability of other acyl carrier proteins.

PMID- 17555525
TI  - Autism spectrum disorders in children with seizures in the first year of life - a
      population-based study.
AB  - PURPOSE: To describe autistic spectrum disorders (ASDs) in a cohort of children
      with history of unprovoked seizures other than infantile spasms in the first year
      of life. METHODS: The source of data was computer records from all the three
      pediatric departments in Iceland. Children diagnosed 1982-2000 with unprovoked
      seizures with onset between 28 days and 12 months of age (N = 102) were invited
      to participate in a study. Children with known developmental disorders and those
      whose parents had concerns regarding their child's development or behavior were
      investigated for possible ASD. Parents were asked to complete the Social
      Communication Questionnaire and children scoring 10 points or higher were further
      examined with the Autism Diagnostic Interview-Revised and observational measures.
      RESULTS: Eighty-four children (82.4%), 28 boys and 56 girls, participated in the
      study and 36.9% (31/84) were investigated for possible ASD. Twenty-four (28.6%)
      had at least one neurodevelopmental disorder, 14.3% had mental retardation (MR),
      and six (7.1%) were diagnosed with ASD, all of whom also had MR and three of whom
      had congenital brain abnormalities. CONCLUSION: These results suggest that the
      estimated prevalence of ASD is higher in children with history of seizure in the
      first year of life than it is in the general population. There are indications
      that support the view that children with ASD and history of seizure in the first
      year of life have higher prevalence of congenital brain abnormalities and are
      more often female, than other children with ASD.

PMID- 17555526
TI  - Reversible effects of antiepileptic drugs on reproductive endocrine function in
      men and women with epilepsy--a prospective randomized double-blind withdrawal
      study.
AB  - PURPOSE: Epilepsy, antiepileptic drugs (AEDs), and reproductive endocrine
      function have complex interactions. In this study, we wanted to investigate the
      effects of AEDs on reproductive endocrine function after withdrawal of AEDs and
      look for reversible endocrine effects. METHODS: The study was prospective,
      randomized, and double-blinded. A total of 160 patients were included and
      randomized to withdrawal or not and 150 (80 females, 53%) patients went through
      the intervention and was included in the study for 12 months. Complete serum
      samples from before and 4 months after completed withdrawal/no withdrawal were
      obtained from 130 patients (63 females, 48%). RESULTS: The main finding was that
      reversible endocrine changes in sex steroid hormone levels could be observed in
      both sexes after withdrawal of AEDs. For CBZ, which was the drug used by the
      majority of the patients, withdrawal led to significant increases in serum
      testosterone concentrations and free androgen index (FAI) in both men (n = 19)
      and women (n = 19). Mean differences in change in FAI between the withdrawal
      group and nonwithdrawal group were in men 17.49 (CI 10.16-24.81, p <or= 0.001),
      and in women 1.61 (CI 0.62-2.61, p <or= 0.001). CONCLUSION: Our findings provide
      further evidence of the potentially negative effects of CBZ treatment on
      reproductive endocrine functions in men and women, but also show that some of
      these changes may be reversible, even after years on treatment.

PMID- 17555527
TI  - Radiation of the rat brain suppresses seizure-induced neurogenesis and
      transiently enhances excitability during kindling acquisition.
AB  - PURPOSE: Adult hippocampal neurogenesis is enhanced in several models for
      temporal lobe epilepsy (TLE). In this study, we used low-dose whole brain
      radiation to suppress hippocampal neurogenesis and then studied the effect of
      this treatment on epileptogenesis in a kindling model for TLE. METHODS: Half of
      the rats were exposed to a radiation dose of 8 Gy one day before the initiation
      of a rapid kindling protocol. Afterdischarge threshold (ADT), afterdischarge
      duration (ADD), clinical seizure severity, and inflammation were compared between
      groups. On the first and third day after radiation, rats were injected with 5'
      bromo-2'-deoxyuridine (BrdU) to evaluate neurogenesis. Seven and 21 days after
      radiation, numbers of doublecortin (DCX) positive neuroblasts in subgranular zone
      and granule cell layer were compared between groups. RESULTS: We showed that
      radiation significantly suppressed neurogenesis and neuroblast production during
      kindling acquisition. Radiation prevented an increase in ADT that became
      significantly lower in radiated rats. On the third and fourth kindling
      acquisition day radiated rats developed more severe seizures more rapidly, which
      resulted in a significantly higher mean severity score on these days. Differences
      in ADD could not be demonstrated. DISCUSSION: Our results demonstrate that brain
      radiation with a relatively low dose effectively suppressed the generation of new
      granule cells and transiently enhanced excitability during kindling acquisition.
      Although seizure-induced neurogenesis was lower in the radiated rats we could not
      detect a strong effect on the final establishment of the permanent fully kindled
      state, which argues against a prominent role of seizure-induced neurogenesis in
      epileptogenesis.

PMID- 17555528
TI  - A probable causative factor for an old problem: selenium and glutathione
      peroxidase appear to play important roles in epilepsy pathogenesis.
AB  - PURPOSE: Only recently has it become known that oxidative stress and generation
      of reactive oxygen species are the cause and the consequence of epileptic
      seizures. Due to the protective role of selenium (Se) and selenoproteins against
      oxidative damage and the ability to promote neuronal cell survival, we compared
      serum selenium level and red blood cell Glutathione peroxidase activity (RBC GPx)
      between epileptic and healthy children. METHODS: In a case control study, 53
      epileptic children were compared with 57 healthy children in the same age and
      community of residence. Serum Se and RBC GPx activity were measured with an
      atomic absorption spectrophotometry and Cayman standard glutathione assay kit,
      respectively. RESULTS: The mean (+/-standard deviation) of serum Se was 72.90
      microg/L (+/-22.20) and 86.00 microg/L (+/-15.00) in patient and control groups,
      respectively. For RBC GPx activity the mean (+/-standard deviation) was 440.57
      nmol/min/ml (+/-264.00) and 801.00 nmol/min/ml (+/-267.00) in patient and control
      groups, respectively. Statistical analysis showed a significant lower means of
      serum Se and RBC GPx activity in patient group compared to that of healthy
      control group (p < 0.001). CONCLUSION: Lower serum Se and RBC GPx activity in
      epileptic patients compared to healthy children may support the proposed crucial
      role of Se and GPx activity in the pathogenesis of epilepsy. However, RBC GPx
      activity in the case of selenium deficiency could not be a sensitive and specific
      indicator of Se status in serum that led us to supplant Se measurement with RBC
      GPx activity.

PMID- 17555529
TI  - Coxiella burnetii infection in C57BL/6 mice aged 1 or 14 months.
AB  - The objective of this study was to investigate the effects of age on infection
      with Coxiella burnetii, the agent of Q fever. Bacterial burden and granuloma
      number were increased in the spleens of 14-month-old as compared with 1-month-old
      mice. This increase was not the result of an anti-inflammatory macrophage
      response, because inflammatory and anti-inflammatory cytokines were induced in
      macrophages from young mice but were repressed in mature mice. In addition,
      macrophage microbicidal competence was similar in mature and young mice. These
      results suggest the importance of individual host factors in the pathophysiology
      of an infectious disease such as Q fever.

PMID- 17555530
TI  - Weekly risedronate in kidney transplant patients with osteopenia.
AB  - Daily bisphosphonate is effective in preventing and treating corticosteroid
      induced osteoporosis in renal transplant recipients, although it frequently has
      gastrointestinal side effects. The aim was to assess efficacy and side effect
      profile of weekly oral risedronate. Eighty-four renal transplant patients,
      receiving either cyclosporin A or tacrolimus and steroids were prospectively
      included. The study group (39 patients) received 35 mg risedronate weekly,
      vitamin D and calcium, while control group (45 patients) only vitamin D and
      calcium. At baseline, 6 and 12 months, creatinine, calcium, phosphorus, alkaline
      phosphatase and iPTH were determined. Fractures and bone mineral densities were
      assessed by X-rays and dual-energy X-ray absorptiometry, respectively. Pain was
      assessed by clinical interview. Mineral bone density score increased
      significantly in risedronate group after 1 year. There were no differences in the
      incidence of fractures, although, anamnestic pain assessment revealed that 3% of
      treatment group reported to have bone pain compared with 18% in nontreatment
      group (P < 0.05). Follow-up calcium, phosphorus, alkaline phosphatases, and iPTH
      levels showed no differences from basal measures. Risedronate was well tolerated
      with no major side effects. Weekly oral risedronate in renal transplanted
      patients reduces bone mineral loss and bone pain and has an excellent side effect
      profile.

PMID- 17555531
TI  - Stem cells and cardiac regeneration.
AB  - Despite many advances in cardiovascular medicine, heart failure (HF) remains the
      leading cause of death in developed countries affecting at least 10 million
      people in Western Europe alone. The poor long-term prognosis of HF patients, and
      immense public health implications has fuelled interest in finding new
      therapeutic modalities. Recent observations of the beneficial effect of stem
      cells on the damaged heart in animal experiments have generated tremendous
      excitement and stimulated clinical studies suggesting that this approach is
      feasible, safe, and potentially effective in humans. Cell-based myocardial
      regeneration is currently explored for a wide range of cardiac disease states,
      including acute and chronic ischemic myocardial damage, cardiomyopathy and as
      biological heart pacemakers. The aim of the present manuscript is to review the
      work that has been done to establish the role of stem cells in cardiac repair,
      give an update on the clinical trials performed so far, as well as to discuss
      critically the controversies, challenges and future surrounding this novel
      therapeutic concept.

PMID- 17555532
TI  - A cytoplasmic PPPSP motif determines megalin's phosphorylation and regulates
      receptor's recycling and surface expression.
AB  - Megalin is a large endocytic receptor expressed at the apical surface of several
      absorptive epithelia. It binds multiple ligands including apolipoproteins,
      vitamin and hormone carrier proteins and signaling molecules such as parathyroid
      hormone and the morphogen sonic hedgehog. An important characteristic of megalin
      is its high endocytic activity, which is mediated by tyrosine-based endocytic
      motifs within the receptor's cytoplasmic tail. This domain also harbors several
      putative consensus phosphorylation motifs for protein kinase (PK) C and casein
      kinase-II and one consensus motif for PKA and glycogen synthase kinase-3 (GSK3).
      Here we report that the cytoplasmic domain of megalin is constitutively
      phosphorylated depending on the integrity of a PPPSP motif, a putative GSK3 site,
      with a minor participation of the other phosphorylation motifs. Mutation of the
      serine residue within the PPPSP motif as well as blocking GSK3 activity, with two
      different inhibitors, significantly decreased the phosphorylation levels of the
      receptor. Both the megalin PPPAP mutant and the underphosphorylated wild-type
      receptor, by inhibition of GSK3 activity, were more expressed at the cell surface
      and more efficiently recycled, but they were not inhibited in their initial
      endocytosis rates. Altogether, these results show that the PPPSP motif and the
      GSK3 activity are critical to allow megalin phosphorylation and also negatively
      regulate the receptor's recycling.

PMID- 17555533
TI  - Innate immune recognition triggers secretion of lysosomal enzymes by macrophages.
AB  - Gamma interferon-induced lysosomal thiolreductase (GILT) is expressed
      constitutively in antigen-presenting cells, where it reduces disulfide bonds to
      facilitate antigen presentation. GILT is synthesized as an enzymatically active
      precursor protein and is processed in early endosomes to yield the mature enzyme.
      The exposure of the promonocytic cell line THP-1 to Escherichia coli causes a
      differentiation-dependent induction of GILT expression in which the majority of
      precursor GILT is secreted as active enzyme. We confirm this result in cultured
      primary monocytes and macrophages, and demonstrate, as an in vivo correlate of
      the phenomenon, upregulation of precursor GILT levels in the serum of mice
      injected with lipopolysaccharide. We show that macrophage differentiation is
      accompanied by a transcriptional downregulation of mannose-6-phosphorylation,
      which likely prevents the recognition and proper sorting of soluble lysosomal
      enzymes by the mannose-6-phosphate receptors. We provide evidence for a mechanism
      of generalized soluble lysosomal enzyme secretion through the constitutive
      secretory pathway.

PMID- 17555534
TI  - Light chain C-terminal region reinforces the stability of clathrin heavy chain
      trimers.
AB  - The self-assembly of clathrin into lattices relies on the ability of heavy chain
      legs to form a three-legged pinwheel structure. We investigated the role of light
      chains in clathrin trimerization by challenging recombinant hub (plus and minus
      light chain) with an anionic detergent. The binding of light chain increases the
      amount of detergent needed to induce detrimerization, suggesting light chains
      reinforced hub trimers. We also show that light chain C-terminal residues are
      important for enhancing the in vitro assembly of hub at low pH. We assessed how
      much the C-terminus of light chain contributed to the stability of the
      trimerization domain by adding full-length and truncated light chains to trimer
      defective hub mutants, C1573S and C1573A. Adding full-length LCb to C1573S caused
      some retrimerization, but little activity was restored, suggesting the majority
      of oligomeric C1573S was nonnative. A larger percentage of monomeric C1573A could
      be retrimerized into an assembly-competent form by adding intact LCb. We also
      discovered that C-terminally deleted light chains produced a heterogeneous
      population of hubs that were smaller than native hubs, but were assembly active.
      We propose a model showing how light chains reinforce the puckered clathrin
      triskelion. Finally, the ability of light chains to retrimerize C1573A hub
      suggests that the structural role of light chain may be conserved in yeast and
      mammals.

PMID- 17555535
TI  - Specificity, promiscuity and localization of ARF protein interactions with NCS-1
      and phosphatidylinositol-4 kinase-III beta.
AB  - ADP-ribosylation factor (ARF) proteins are involved in multiple intracellular
      vesicular transport pathways. Most studies have focused on the functions of ARF1
      or ARF6 and little is known about the remaining ARF isoforms. Although the
      mammalian ARF proteins share a high degree of sequence identity, recent evidence
      has indicated that they may control distinct trafficking steps within cells. A
      unanswered issue is the degree of specificity of ARF family members for different
      interacting proteins. To investigate potential functional differences between the
      human ARF proteins, we have examined the localization of all human ARF isoforms
      and their interactions with two ARF1 binding proteins, neuronal calcium sensor-1
      (NCS-1) and phosphatidylinositol-4 kinase-IIIbeta (PI4Kbeta). Use of a
      fluorescent protein fragment complementation method showed direct interactions
      between ARFs 1, 3, 5 and 6 with NCS-1 but at different intracellular locations in
      live HeLa cells. Photobleaching experiments indicated that complementation did
      not detect dynamic changes in protein interactions over short-time scales. A more
      specific interaction between ARFs 1/3 and PI4Kbeta was observed. Consistent with
      these latter findings ARF1 but not ARF5 or 6 enhanced the stimulatory effect of
      PI4Kbeta on regulated exocytosis, suggesting a specific role for class-I ARFs in
      the regulation of PI4Kbeta.

PMID- 17555536
TI  - Defective CFTR apical endocytosis and enterocyte brush border in myosin VI
      deficient mice.
AB  - In polarized epithelial cells such as those that line the inner ear, kidney and
      gut, myosin VI has been localized to the intermicrovillar domains where it is
      proposed to regulate clathrin-dependent endocytosis; however, a direct role for
      myosin VI in apical endocytosis has not been shown. We examined the apical
      membrane distribution and endocytosis of cystic fibrosis transmembrane
      conductance regulator (CFTR) in myosin VI-deficient Snell's Waltzer Myo6((sv/sv))
      mice. Confocal microscopy and cell-surface biotinylation confirmed that surface
      levels of CFTR in the intestine of Myo6((sv/sv)) mice were markedly higher, and
      CFTR internalization from the apical plasma membrane was reduced compared with
      heterozygous controls. Consistent with a defect in CFTR endocytosis and
      accumulation at the cell surface, exaggerated CFTR-mediated fluid secretion was
      observed in Myo6((sv/sv)) mice following treatment of isolated jejunum with the
      cyclic GMP-activated heat stable enterotoxin. These data establish that myosin VI
      modulates apical endocytosis and may be an important physiological modulator of
      CFTR function and CFTR-associated secretory diarrhea in the gut.

PMID- 17555537
TI  - Alterations of atrial natriuretic peptide in cardiomyocytes and plasma of rats
      after different intensity exercise.
AB  - To characterize the effect of long-term exercise training at different
      intensities on endocrine structure and function of the heart, plasma atrial
      natriuretic peptide (ANP) levels, expression of ANP in cardiomyocytes, and
      ultrastructure of cardiomyocytes were examined by radioimmunoassay,
      immunohistochemistry and transmission electron microscopy in Sprague-Dawley rats
      trained on a treadmill at different intensities for 8 weeks. The plasma ANP
      increased gradually with increasing exercise intensity. The immunoreactivity of
      ANP in cardiomyocytes increased in the moderate- and high-intensity exercise
      group and decreased in the exhaustive exercise group. The ANP electron-dense
      granules and the quantity and volume of mitochondria increased in moderate and
      high-intensity exercise group. The ANP electron dense granules decreased and the
      mitochondria tumefied in the exhaustive exercise group. The changes of plasma ANP
      have a tendency of increasing gradually with increase in exercise intensity.
      Moderate and high-intensity exercise increases ANP synthesis and storage in
      cardiomyocytes and induces adaptive changes in the ultrastructure of
      cardiomyocytes. The decrease of ANP immunoreactivity in cardiomyocytes after
      exhaustive exercise is probably the result of massive depletion and induces
      damaging changes in the ultrastructure of cardiomyocytes.

PMID- 17555538
TI  - Prevalence and incidence of lower extremity injuries in male marathon runners.
AB  - The aim of this study is to describe the prevalence and incidence of lower
      extremity injuries occurring before and during the Rotterdam marathon, and to
      evaluate the impact of the injuries. A cohort study was compiled of recreational
      male participants in the 2005 Rotterdam marathon. Demographic data and
      information on previous injuries were obtained from participants using a baseline
      questionnaire. Information on injuries sustained shortly before or during the
      marathon was obtained from a post-race questionnaire. Seven hundred and twenty
      five (48.3%) participants returned the baseline questionnaire. The 1-year
      prevalence of running injuries was 54.8%. In the post-race questionnaire, 15.6%
      of all respondents reported at least one new lower extremity injury in the month
      preceding the Rotterdam marathon. The incidence of lower extremity injuries
      occurring during the marathon was 18.2%; most of these injuries occurred in the
      calf, knee and thigh. Immediately after the marathon the median score of pain
      intensity at rest was 2 points vs 4.5 points during physical exercise. Hence we
      can conclude that running injuries are very common among recreational male
      marathon runners. However, the pain severity and consequences for work and daily
      activities seem to be relatively low 1 week after the marathon.

PMID- 17555539
TI  - Physical activity on prescription in primary health care: a follow-up of physical
      activity level and quality of life.
AB  - To examine whether physical activity on prescription in routine primary care
      patients would influence physical activity level and quality of life 6 months
      later. In 2001-2003, 13 Swedish primary health care units took part in an
      uncontrolled clinical study. If a patient in primary health care needed physical
      activity preventively or for treatment of a disease and patient-centered
      motivational counseling found physical activity to be suitable, individualized
      physical activity could be prescribed. Patients (n=481) of both sexes and all
      ages [75% women, mean age 50 (12-81)] participated in the study. Self-reported
      physical activity, readiness to change to a more physically active lifestyle and
      quality-of-life data were collected through questionnaires. The follow-up rate
      was 62% at 6 months. Intention-to-treat analysis showed a significant increase
      (P<0.01) in self-reported physical activity level, the stages of action and
      maintenance of physical activity as well as quality of life. Physical activity
      level, stages of change and quality of life increased analogically, indicating
      that physical activity on prescription may be suitable as a conventional
      treatment in an ordinary primary health care setting to promote a more physically
      active lifestyle.

PMID- 17555540
TI  - Homocysteine status in former top-level male athletes: possible effect of
      physical activity and physical fitness.
AB  - The importance of elevated homocysteine (Hcy) as a risk marker for cardiovascular
      disease is continuously under debate. Lifestyle factors may increase the total
      Hcy (tHcy) level of the plasma, but there are no consistent findings relating to
      Hcy, physical activity, and cardiorespiratory fitness. Cross-sectional
      measurement from an ongoing follow-up study was performed on 77 former male
      athletes and 33 sedentary controls (age range 35-62 years). Lifestyle parameters
      (current physical activity patterns, smoking, etc.), anthropometric and blood
      pressure data, and data about tHcy, reduced, and oxidized glutathione (GSH, GSSG,
      respectively) in blood, lipoproteins, and maximal oxygen consumption (VO(2max))
      were collected. Our study results showed that the subgroup of physically active
      ex-athletes (n=52) had a significantly lower tHcy level and glutathione redox
      ratio (GSSG:GSH) in comparison with the subgroup of sedentary ex-athletes (n=25).
      tHcy level was inversely related to cardiorespiratory fitness (VO(2max)/kg).
      Dietary and smoking habits were not significantly associated with the tHcy level
      in our study group. In conclusion, the research findings indicate that both
      current physical activity and cardiorespiratory fitness are significantly
      inversely associated with an elevated homocysteine level in middle-aged former
      athletes.

PMID- 17555541
TI  - Sources of variation in habitual physical activity of children and adolescents:
      the European youth heart study.
AB  - The present study examined the influence of gender, maturity state, seasonality,
      type of measurement day and socioeconomic status (SES) on habitual physical
      activity in 8-10-year-old children and 14-16-year-old adolescents (n=1318).
      Physical activity was assessed objectively by accelerometry. The results showed a
      significant effect of the type of measurement day on physical activity with a
      general pattern of lower activity levels in weekends compared with weekdays.
      Furthermore, higher physical activity levels were observed during the months of
      spring/summer compared with the months of autumn/winter for the 8-10-year-olds,
      whereas no significant effect of months was observed for the 14-16-year-olds,
      possibly due to exam preparations and lack of physical activity registration
      during the months of summer for this cohort. SES was unrelated to physical
      activity in the 8-10-year-olds, whereas an inverse association was observed in
      the 14-16-year-olds. However, a post hoc analysis provided strong evidence that
      this latter result was biased by the accelerometers inability to pick up
      bicycling activities. Finally, boys were more physically active compared with
      girls, and maturity state was unrelated to physical activity. The results could
      prove useful for working out strategies to prevent inactivity and for adjusting
      for temporal sources of variation in physical activity in future studies.

PMID- 17555542
TI  - Tracking of objectively measured physical activity from childhood to adolescence:
      the European youth heart study.
AB  - A number of studies have investigated tracking of physical activity from
      childhood to adolescence and, in general, these studies have been based on
      methods with some degree of subjectivity (e.g., questionnaires). The aim of the
      present study was to evaluate tracking of physical activity from childhood to
      adolescence using accelerometry, taking into account major sources of variation
      in physical activity. Both a crude and an adjusted model was fitted, and, in the
      adjusted model, analyses were corrected for seasonal variation, within-week
      variation, activity registration during night time sleep, within instrumental
      measurement error, and day-to-day variation in physical activity. In all, 208
      subjects were included in the crude analyses. Stability coefficients estimated
      from the crude model were low (i.e., 0.18 and 0.19 for boys and girls,
      respectively) and only borderline significant. However, in the adjusted model
      highly significant stability coefficients of 0.53 and 0.48 for boys and girls,
      respectively, were observed. It was concluded that physical activity behavior
      tends to track moderately from childhood to adolescence.

PMID- 17555543
TI  - Achievement involvement and stress coping in elite wrestling.
AB  - The present study explored the relationship between task involvement and coping
      with stress in elite competition. Participants were 82 elite wrestlers, both male
      (n=60) and female (n=22), from four different European countries, age 16-37. The
      data for the study were gathered over an 18-month period, and both qualitative in
      depth interviews (n=6) and quantitative approaches were used. The quantitative
      study measured motivation from an achievement goal theory perspective:
      achievement goal orientation [Perception of Success Questionnaire], perceptions
      of the motivational climate [Perceived Motivational Climate in Sport
      Questionnaire] and coping strategies (Brief COPE). The qualitative part explored
      motivation and coping in depth. As expected, task involved wrestlers coped better
      in competitive situations due to their use of more adaptive coping strategies.
      The wrestlers' experiences seemingly make them prefer to stay task involved and
      use adaptive coping strategies (both problem-focused and emotion-focused
      strategies) in competition.

PMID- 17555544
TI  - A rat model of saliva secretory immunoglobulin: a suppression caused by intense
      exercise.
AB  - We aimed to develop a valid model of immunosuppression induced by intense
      exercise in rats. Rats were divided into three groups. In the rest (Rest) group,
      saliva was collected from resting rats on 4 consecutive days. In the exercise
      (Ex) group, rats ran on a treadmill until exhaustion (exercise time: 60.0 +/- 3.7
      min), and their saliva was collected before and after exercise; the salivary
      glands were removed after exercise. In the control (Con) group, saliva collection
      and gland removal were also performed, but the rats did not exercise. Secretory
      immunoglobulin A (SIgA) concentrations in saliva and polymeric immunoglobulin
      receptor (pIgR) mRNA expression in the glands were measured. There was no
      significant change in SIgA concentration in the Rest group over 4 days. In the Ex
      group, SIgA concentration decreased significantly after exercise compared with
      before, whereas there was no significant change in the Con group. The expression
      of pIgR mRNA was significantly lower in the Ex group post-exercise than in the
      Con group. Our procedure for saliva collection appeared suitable, and the
      exercise-induced SIgA suppression was probably caused by a decline in pIgR mRNA
      expression. We propose to use this reproducible and reliable rat model of
      exercise-induced SIgA suppression in future studies.

PMID- 17555545
TI  - A functional comparison of the hyolingual complex in pygmy and dwarf sperm whales
      (Kogia breviceps and K. sima), and bottlenose dolphins (Tursiops truncatus).
AB  - The function of the hyolingual complex in three odontocete species was
      investigated to compare adaptations of divergent feeding strategies, suction and
      ram feeding. Pygmy and dwarf sperm whales, members of the genus Kogia (or
      kogiids), are known to be strong suction feeders. We tested the hypotheses that
      kogiids would have a larger, more robust hyolingual complex, and that hyolingual
      muscles would have a greater maximum theoretical muscle tension compared with ram
      based feeders such as bottlenose dolphins (Tursiops truncatus). A robustness
      index and surface area was calculated for bony hyoid elements in kogiids and
      bottlenose dolphins. The anatomy, muscle architecture, pinnation, two-dimensional
      angle of attachment and maximum theoretical muscle tension were measured in each
      hyolingual muscle. A functional model incorporating vector analyses of hyolingual
      musculature was created for kogiids and bottlenose dolphins to assess differences
      in function of their hyolingual complexes. Kogiid hyoid surface areas were
      significantly greater (P = 0.01) than in bottlenose dolphins. Most maximum
      theoretical muscle tensions of hyolingual complexes were not significantly
      different within or between species. The data suggest that associated orofacial
      and tongue morphology, particularly the relationship of hyoid shape and tongue
      retractor muscles, greatly influences suction capability in odontocetes. Kogiids
      demonstrated adaptations that occlude lateral gape, including a novel vertical
      ridge on each side of the mandible, and a shortened mandible that is capable of a
      large gape, and gape angle. These adaptations presumably assist in maintaining
      negative intraoral pressure generated by the depression and retraction of the
      relatively short and wide kogiid tongue. The tongues of kogiids should be capable
      of generating greater intraoral volume changes compared with the long, narrow
      tongue of bottlenose dolphins.

PMID- 17555546
TI  - Bone morphogenetic protein rescues the lack of secondary cartilage in Runx2
      deficient mice.
AB  - Secondary cartilages including mandibular condylar cartilage have unique
      characteristics. They originate from alkaline phosphatase (ALP)-positive
      progenitor cells of the periosteum, and exhibit characteristic modes of
      differentiation. They also have a unique extracellular matrix, and coexpress type
      I, II and X collagens. We have previously shown that there is a total absence of
      secondary cartilages in Runx2-deficient (Runx2-/-) mice. To clarify whether Runx2
      is essential for chondrocytic differentiation of secondary cartilages, we
      performed an organ culture system using mandibular explants derived from Runx2-/-
      mice at embryonic day 18.0. Since mRNA for bone morphogenetic protein 2 (BMP2)
      was strongly expressed in osteoblasts of condylar anlagen in wild-type mice, and
      was down-regulated in those of Runx2-/- mice, we chose to investigate BMP2
      effects on secondary cartilage formation. Condensed mesenchymal cells of
      mandibular condylar anlagen in precultured explants were ALP-positive and
      expressed type I collagen and Sox9. After culture with recombinant human (rh)
      BMP2, chondrocytic cells showing ALP activity and expressing Sox5, Sox9, and type
      I and II collagens, appeared from mesenchymal condensation. This expression
      profile was comparable with the reported pattern of chondrocytes in mouse
      secondary cartilages. However, chondrocyte hypertrophy was not observed in the
      explants. These findings indicate that BMP2 partially rescued chondrocyte
      differentiation but not chondrocyte hypertrophy in secondary cartilage formation
      in Runx2-/- mice. Runx2 is required for chondrocyte hypertrophy in secondary
      cartilage formation, and it is likely that BMP2, which is abundantly secreted by
      osteoblasts in condylar anlagen, contributes to the early process of secondary
      cartilage formation.

PMID- 17555548
TI  - RET signaling-induced SPHK1 gene expression plays a role in both GDNF-induced
      differentiation and MEN2-type oncogenesis.
AB  - RET, the receptor of glial cell line-derived neurotrophic factor (GDNF) family
      ligands, is important for the development of kidney and peripheral neurons. GDNF
      promotes survival and differentiation of neurons. Mutation of RET leads to the
      constitutive signal activation causing papillary thyroid carcinoma and multiple
      endocrine neoplasia type 2 (MEN2). In this study, we report that GDNF/RET
      signaling up-regulates sphingosine kinase (SPHK) enzyme activity, SPHK1 protein
      and SPHK1 message in TGW human neuroblastoma cells. Silencing of SPHK1 using
      siRNA inhibited GDNF-induced neurite formation, GAP43 expression, and cell
      growth, suggesting the important role of SPHK1 in GDNF signal transduction.
      Furthermore, NIH3T3 cells transfected with MEN2A type mutated RET but not c-RET
      demonstrated the up-regulation of SPHK activity, SPHK1 protein and SPHK1 message
      compared with NIH3T3 cells. The cell growth and anchorage-independent colony
      formation of MEN2A-NIH3T3 was inhibited with siRNA of SPHK1, while no effect of
      scramble siRNA was observed. These results suggest the oncogenic role of SPHK1 in
      MEN2A type tumor. Promoter analysis showed that activator protein 2 and
      specificity protein 1 binding motif of the 5' promoter region of SPHK1 gene is
      important for its induction by GDNF. Furthermore, we demonstrated that ERK1/2 and
      PI3 kinase are involved in GDNF-induced SPHK1 transcription by using specific
      inhibitors.

PMID- 17555549
TI  - Prostaglandin synthesis in rat brain astrocytes is under the control of the n-3
      docosahexaenoic acid, released by group VIB calcium-independent phospholipase A2.
AB  - In the current study, we reveal that in astrocytes the VIB Ca(2+)-independent
      phospholipase A(2) is the enzyme responsible for the release of docosahexaenoic
      acid (22:6n-3). After pharmacological inhibition and siRNA silencing of VIB
      Ca(2+)-independent phospholipase A(2), docosahexaenoic acid release was strongly
      suppressed in astrocytes, which were acutely stimulated (30 min) with ATP and
      glutamate or after prolonged (6 h) stimulation with the endotoxin
      lipopolysaccharide. Docosahexaenoic acid release proceeds simultaneously with
      arachidonic acid (20:4n-6) release and prostaglandin liberation from astrocytes.
      We found that prostaglandin production is negatively controlled by endogenous
      docosahexaenoic acid, since pharmacological inhibition and siRNA silencing of VIB
      Ca(2+)-independent phospholipase A(2) significantly amplified the prostaglandin
      release by astrocytes stimulated with ATP, glutamate, and lipopolysaccharide.
      Addition of exogenous docosahexaenoic acid inhibited prostaglandin synthesis,
      which suggests that the negative control of prostaglandin synthesis observed here
      is likely due to competitive inhibition of cyclooxygenase-1/2 by free
      docosahexaenoic acid. Additionally, treatment of astrocytes with docosahexaenoic
      acid leads to the reduction in cyclooxygenase-1 expression, which also
      contributes to reduced prostaglandin production observed in lipopolysaccharide
      stimulated cells. Thus, we identify a regulatory mechanism important for the
      brain, in which docosahexaenoic acid released from astrocytes by VIB Ca(2+)
      independent phospholipase A(2) negatively controls prostaglandin production.

PMID- 17555547
TI  - Central nervous system regulation of mammalian hibernation: implications for
      metabolic suppression and ischemia tolerance.
AB  - Torpor during hibernation defines the nadir of mammalian metabolism where whole
      animal rates of metabolism are decreased to as low as 2% of basal metabolic rate.
      This capacity to decrease profoundly the metabolic demand of organs and tissues
      has the potential to translate into novel therapies for the treatment of ischemia
      associated with stroke, cardiac arrest or trauma where delivery of oxygen and
      nutrients fails to meet demand. If metabolic demand could be arrested in a
      regulated way, cell and tissue injury could be attenuated. Metabolic suppression
      achieved during hibernation is regulated, in part, by the central nervous system
      through indirect and possibly direct means. In this study, we review recent
      evidence for mechanisms of central nervous system control of torpor in
      hibernating rodents including evidence of a permissive, hibernation protein
      complex, a role for A1 adenosine receptors, mu opiate receptors, glutamate and
      thyrotropin-releasing hormone. Central sites for regulation of torpor include the
      hippocampus, hypothalamus and nuclei of the autonomic nervous system. In
      addition, we discuss evidence that hibernation phenotypes can be translated to
      non-hibernating species by H(2)S and 3-iodothyronamine with the caveat that the
      hypothermia, bradycardia, and metabolic suppression induced by these compounds
      may or may not be identical to mechanisms employed in true hibernation.

PMID- 17555550
TI  - Rapid down-regulation of Ret following exposure of dopaminergic neurons to
      neurotoxins.
AB  - The survival and functional maintenance of vertebrate neurons depends on the
      availability of specific neurotrophic factors. We studied the influence of
      neurotrophic support on responses of dopaminergic neurons to 1-methyl-4-phenyl
      1,2,3,6-tetrahydropyridine, a neurotoxin known to damage the nigrostriatal
      dopaminergic pathway in humans and other mammals. Treatment of mice with 1-methyl
      4-phenyl-1,2,3,6-tetrahydropyridine caused decreases in levels of Ret, a tyrosine
      kinase receptor for glial cell line-derived neurotrophic factor (GDNF) in the
      striatum, under the condition in which tyrosine hydroxylase was moderately
      decreased and the GDNF family receptor alpha1, another receptor of GDNF that is
      the ligand-binding subunit, were unaffected. Down-regulation of Ret was also
      observed in dopamine-producing PC12 cells undergoing apoptosis induced by
      rotenone, another toxic substance for dopaminergic neurons, while other cellular
      components were not affected. Ret was also extremely vulnerable to other
      apoptotic inducing conditions. Taken together, these results indicate that Ret,
      an important signal molecule in dopaminergic neurons, may be down-regulated in
      the early stages of neuronal degeneration caused by various neurotoxic
      substances, and may lead to reduced neurotrophic influences.

PMID- 17555551
TI  - A comparison of the high-affinity peripheral benzodiazepine receptor ligands
      DAA1106 and (R)-PK11195 in rat models of neuroinflammation: implications for PET
      imaging of microglial activation.
AB  - Activated microglia are an important feature of many neurological diseases and
      can be imaged in vivo using 1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3
      isoquinolinecarboxamide (PK11195), a ligand that binds the peripheral
      benzodiazepine receptor (PBR). N-(2,5-dimethoxybenzyl)-N-(5-fluoro-2
      phenoxyphenyl) acetamide (DAA1106) is a new PBR-specific ligand that has been
      reported to bind to PBR with higher affinity compared with PK11195. We
      hypothesized that this high-affinity binding of DAA1106 to PBR will enable better
      delineation of microglia in vivo using positron emission tomography.
      [(3)H]DAA1106 showed higher binding affinity compared with [(3)H](R)-PK11195 in
      brain tissue derived from normal rats and the rats injected intrastriatally with
      6-hydroxydopamine or lipopolysaccharide at the site of the lesion.
      Immunohistochemistry combined with autoradiography in brain tissues as well as
      correlation analyses showed that increased [(3)H]DAA1106 binding corresponded
      mainly to activated microglia. Finally, ex vivo autoradiography and positron
      emission tomography imaging in vivo showed greater retention of [(11)C]DAA1106
      compared with [(11)C](R)-PK11195 in animals injected with either
      lipopolysaccaride or 6-hydroxydopamine at the site of lesion. These results
      indicate that DAA1106 binds with higher affinity to microglia in rat models of
      neuroinflammation when compared with PK11195, suggesting that [(11)C]DAA1106 may
      represent a significant improvement over [(11)C](R)-PK11195 for in vivo imaging
      of activated microglia in human neuroinflammatory disorders.

PMID- 17555552
TI  - Apoptotic action of E2F1 requires glycogen synthase kinase 3-beta activity in
      PC12 cells.
AB  - Both E2F1 and GSK3beta have been described as essential targets in neuronal
      apoptosis. Previous studies have demonstrated that GSK3beta binds to E2F1 in
      vivo. We wanted to investigate whether these proteins could share a common
      apoptotic signal pathway in neuronal cells. With this intention, we developed a
      PC12 ER-E2F1 stable cell line in which E2F1 activity was dependent on the
      presence of 4-hydroxitamoxifen. E2F1 activation produced apoptosis in naive and
      post-mitotic cells; serum and nerve growth factor respectively protected them
      from E2F1 apoptotic stimuli. The presence of specific GSK3beta inhibitors
      SB216763 and LiCl completely protected cells from apoptosis induced by E2F1
      activation. In addition, knocked down GSK3beta experiments by small interference
      RNAs have demonstrated that a reduction of GSK3beta protein levels can lower the
      apoptotic effect of E2F1. Finally, we demonstrated that the apoptotic effect of
      E2F1 is not due to the regulation of GSK3beta activity, and that the inhibitory
      effect of GSK3beta inhibitor SB216763 on E2F1 induced apoptosis could be due to
      an alteration in the E2F1-regulated transcription gene pattern. In summary, we
      have demonstrated that the apoptotic action of E2F1 requires GSK3beta activity.

PMID- 17555553
TI  - Enhancement of alpha-secretase cleavage of amyloid precursor protein by a
      metalloendopeptidase nardilysin.
AB  - Amyloid-beta (Abeta) peptide, the principal component of senile plaques in the
      brains of patients with Alzheimer's disease, is derived from proteolytic cleavage
      of amyloid precursor protein (APP) by beta- and gamma-secretases. Alternative
      cleavage of APP by alpha-secretase occurs within the Abeta domain and precludes
      generation of Abeta peptide. Three members of the ADAM (a disintegrin and
      metalloprotease) family of proteases, ADAM9, 10 and 17, are the main candidates
      for alpha-secretases. However, the mechanism that regulates alpha-secretase
      activity remains unclear. We have recently demonstrated that nardilysin (EC
      3.4.24.61, N-arginine dibasic convertase; NRDc) enhances ectodomain shedding of
      heparin-binding epidermal growth factor-like growth factor through activation of
      ADAM17. In this study, we show that NRDc enhances the alpha-secretase activity of
      ADAMs, which results in a decrease in the amount of Abeta generated. When
      expressed with ADAMs in cells, NRDc dramatically increased the secretion of alpha
      secretase-cleaved soluble APP and reduced the amount of Abeta peptide generated.
      A peptide cleavage assay in vitro also showed that recombinant NRDc enhances
      ADAM17-induced cleavage of the peptide substrate corresponding to the alpha
      secretase cleavage site of APP. A reduction of endogenous NRDc by RNA
      interference was accompanied by a decrease in the cleavage by alpha-secretase of
      APP and increase in the amount of Abeta generated. Notably, NRDc is clearly
      expressed in cortical neurons in human brain. Our results indicate that NRDc is
      involved in the metabolism of APP through regulation of the alpha-secretase
      activity of ADAMs, which may be a novel target for the treatment of Alzheimer's
      disease.

PMID- 17555554
TI  - Systemically delivered Erythropoietin transiently enhances adult hippocampal
      neurogenesis.
AB  - Erythropoietin is a primary regulator of erythropoiesis in the hematopoietic
      system. More recently erythropoietin has been shown to play a role in
      neurogenesis and provide neurotrophic support to injured CNS tissue. Here the
      effects of large systemic doses of erythropoietin on basal levels of adult
      hippocampal neurogenesis in mice were examined. A 7-day period of recombinant
      human erythropoietin (rhEPO) administration increased the number of
      bromodeoxyuridine [BrdU(+)] cells in the sub-granular zone (SGZ) by 30%. Analysis
      of cell phenotype revealed an increase in mitotically active doublecortin(+)
      neuronal progenitor cells and glial fibrillary acidic protein(+) SGZ radial
      astrocytes/stem cells but not mature S100beta(+) astrocytes. These effects
      appeared to be mediated, in part, by mitogen-activated protein kinase signaling
      and potentially regulated by suppressor of cytokine signaling-3. Hippocampal
      levels of phosphorylated extracellular signal-related kinase 42/44 and suppressor
      of cytokine signaling-3 were increased 2-6 h after a single systemic rhEPO
      injection. However, rhEPO had no observed effect on the long-term survival of new
      born cells in the SGZ, with similar numbers of BrdU(+) cells and BrdU(+)/NeuN(+)
      co-labeled cells after 4 weeks. Therefore, systemically delivered rhEPO
      transiently increased adult hippocampal neurogenesis without any apparent long
      term effects.

PMID- 17555555
TI  - Optical bioluminescence imaging of human ES cell progeny in the rodent CNS.
AB  - Pre-clinical efforts of grafting human embryonic stem cell (hESC)-derived neural
      precursors have been hampered by problems ranging from graft rejection to
      overgrowth and tumor formation. The ability to detect such potential
      complications sensitively and reliably in clinically relevant contexts will rest
      upon the implementation of suitable non-invasive imaging technologies for
      continuously probing graft survival, proliferation, and migration. Neural
      precursors were transduced ex vivo using a lentiviral-mediated gene delivery
      system expressing firefly D-luciferase, under the control of a cytomegalovirus
      promoter. Transduced cells revealed no loss of cellular morphology, proliferative
      capacity, or neural phenotype in vitro. As a novel approach to monitoring the
      fate of human grafts within the living brain, we adapted optical bioluminescence
      imaging to assess long-term graft viability in immunodeficient mouse models
      transplanted with genetically engineered human neural precursor cells. We
      additionally applied this technology to immunocompetent models for detecting and
      characterizing the time course of graft rejection. Using this strategy, we define
      statistically relevant imaging criteria that can predict graft rejection or
      overgrowth. In conclusion, our data suggest that optical bioluminescence imaging
      can serve as an essential tool for the development of hESC-based grafting
      strategies in the CNS.

PMID- 17555556
TI  - Mutant SOD1(G93A) microglia are more neurotoxic relative to wild-type microglia.
AB  - Recent studies suggest that microglia over-expressing mutant human superoxide
      dismutase (mSOD1(G93A)) may contribute to motoneuron death in a transgenic mouse
      model of familial amyotrophic lateral sclerosis. To further assess the relative
      neurotoxicity of wild-type microglia, mSOD1(G93A) microglia, and microglia over
      expressing wild-type human SOD1, we used primary cultures of microglia and
      motoneurons in the presence and absence of lipopolysaccharide stimulation.
      Following activation with lipopolysaccharide, mSOD1(G93A) microglia released more
      nitric oxide, more superoxide, and less insulin-like growth factor-1 than wild
      type microglia. In microglia/motoneuron co-cultures, mSOD1(G93A) microglia
      induced more motoneuron death and decreased neurite numbers and length compared
      with wild-type microglia. Mutant SOD1(G93A) microglia also induced more
      motoneuron injury than microglia over-expressing wild-type human SOD1 in
      microglia/motoneuron co-cultures. Motoneuron survival was inversely correlated
      with nitrate + nitrite concentrations in mSOD1(G93A) co-cultures, suggesting the
      important role of nitric oxide in microglia-induced motoneuron injury. Thus,
      relative to wild-type microglia, mSOD1(G93A) microglia were more neurotoxic and
      induced more motoneuron injury than similarly treated wild-type microglia.

PMID- 17555557
TI  - Impact of conflict on infant immunisation coverage in Afghanistan: a countrywide
      study 2000-2003.
AB  - BACKGROUND: Infant immunisation is an effective public health intervention to
      reduce the morbidity and mortality of vaccine preventable diseases. However, some
      developing countries fail to achieve desirable vaccination coverage; Afghanistan
      is one such country. The present study was performed to evaluate the progress and
      variation in infant immunisation coverage by district and region in Afghanistan
      and to assess the impact of conflict and resource availability on immunisation
      coverage. RESULTS: This study analysed reports of infant immunisation from 331
      districts across 7 regions of Afghanistan between 2000 and 2003. Geographic
      information system (GIS) analysis was used to visualise the distribution of
      immunisation coverage in districts and to identify geographic inequalities in the
      process of improvement of infant immunisation coverage. The number of districts
      reporting immunisation coverage increased substantially during the four years of
      the study. Progress in Bacillus Calmette-Guerin (BCG) immunisation coverage was
      observed in all 7 regions, although satisfactory coverage of 80% remained
      unequally distributed. Progress in the third dose of Diphtheria-Pertussis-Tetanus
      (DPT3) immunisation differed among regions, in addition to the unequal
      distribution of immunisation coverage in 2000. The results of multivariate
      logistic regression analysis indicated a significant negative association between
      lack of security in the region and achievement of 80% coverage of immunisation
      regardless of available resources for immunisation, while resource availability
      showed no relation to immunisation coverage. CONCLUSION: Although progress was
      observed in all 7 regions, geographic inequalities in these improvements remain a
      cause for concern. The results of the present study indicated that security
      within a country is an important factor for affecting the delivery of
      immunisation services.

PMID- 17555558
TI  - Validity and reliability of the Functioning Assessment Short Test (FAST) in
      bipolar disorder.
AB  - BACKGROUND: Numerous studies have documented high rates of functional impairment
      among bipolar disorder (BD) patients, even during phases of remission. However,
      the majority of the available instruments used to assess functioning have focused
      on global measures of functional recovery rather than specific domains of
      psychosocial functioning. In this context, the Functioning Assessment Short Test
      (FAST) is a brief instrument designed to assess the main functioning problems
      experienced by psychiatric patients, particularly bipolar patients. It comprises
      24 items that assess impairment or disability in six specific areas of
      functioning: autonomy, occupational functioning, cognitive functioning, financial
      issues, interpersonal relationships and leisure time. METHODS: 101 patients with
      DSM-IV TR bipolar disorder and 61 healthy controls were assessed in the Bipolar
      Disorder Program, Hospital Clinic of Barcelona. The psychometric properties of
      FAST (feasibility, internal consistency, concurrent validity, discriminant
      validity (euthymic vs acute patients), factorial analyses, and test-retest
      reliability) were analysed. RESULTS: The internal consistency obtained was very
      high with a Cronbach's alpha of 0.909. A highly significant negative correlation
      with GAF was obtained (r = -0.903; p < 0.001) pointing to a reasonable degree of
      concurrent validity. Test-retest reliability analysis showed a strong correlation
      between the two measures carried out one week apart (ICC = 0.98; p < 0.001). The
      total FAST scores were lower in euthymic (18.55 +/- 13.19; F = 35.43; p < 0.001)
      patients, as compared with manic (40.44 +/- 9.15) and depressive patients (43.21
      +/- 13.34). CONCLUSION: The FAST showed strong psychometrics properties and was
      able to detect differences between euthymic and acute BD patients. In addition,
      it is a short (6 minutes) simple interview-administered instrument, which is easy
      to apply and requires only a short period of time for its application.

PMID- 17555559
TI  - Sensitive and robust gene expression changes in fish exposed to estrogen--a
      microarray approach.
AB  - BACKGROUND: Vitellogenin is a well established biomarker for estrogenic exposure
      in fish. However, effects on gonadal differentiation at concentrations of
      estrogen not sufficient to give rise to a measurable vitellogenin response
      suggest that more sensitive biomarkers would be useful. Induction of zona
      pellucida genes may be more sensitive but their specificities are not as clear.
      The objective of this study was to find additional sensitive and robust candidate
      biomarkers of estrogenic exposure. RESULTS: Hepatic mRNA expression profiles were
      characterized in juvenile rainbow trout exposed to a measured concentration of
      0.87 and 10 ng ethinylestradiol/L using a salmonid cDNA microarray. The higher
      concentration was used to guide the subsequent identification of generally more
      subtle responses at the low concentration not sufficient to induce vitellogenin.
      A meta-analysis was performed with data from the present study and three similar
      microarray studies using different fish species and platforms. Within the
      generated list of presumably robust responses, several well-known estrogen
      regulated genes were identified. Two genes, confirmed by quantitative RT-PCR
      (qPCR), fulfilled both the criteria of high sensitivity and robustness; the
      induction of the genes encoding zona pellucida protein 3 and a nucleoside
      diphosphate kinase (nm23). CONCLUSION: The cross-species, cross-platform meta
      analysis correctly identified several robust responses. This adds confidence to
      our approach used for identifying candidate biomarkers. Specifically, we propose
      that analyses of an nm23 gene together with zona pellucida genes may increase the
      possibilities to detect an exposure to low levels of estrogenic compounds in
      fish.

PMID- 17555560
TI  - Utilization of routinely collected administrative data in monitoring the
      incidence of aging dependent hip fracture.
AB  - Societies are facing challenges as the public health burden increases in tandem
      with population aging. Local information systems are needed that would allow a
      continuous monitoring of the incidence and effectiveness of treatments. This
      study investigates the possibilities of routinely collected administrative data
      as a data source for hip fracture incidence monitoring in Finland. The study
      demonstrates that a straightforward use of register data results in biased
      estimates for the numbers of hip fractures. An interpretation of hip fractures
      from the population aging point of view offers an alternative perspective for hip
      fracture incidence calculation. This enables development of a generalizable
      method for probabilistic detection of starting points of hip fracture care
      episodes. Several risk factor and risk population extraction techniques required
      in register-based data analyses are also demonstrated. Finally, it is shown that
      empirical evidence suggests that hip fracture incidence is proportional to
      population level disability prevalence. In conclusion, Finnish administrative
      data makes it possible to derive data for rather detailed population level risk
      factor stratification. Certain limitations of register-based data can be partly
      avoided by synthesizing data-sensitive methodological solutions during the
      analysis process.

PMID- 17555561
TI  - Molecular response to aromatase inhibitor treatment in primary breast cancer.
AB  - BACKGROUND: Aromatase inhibitors such as anastrozole and letrozole are highly
      effective suppressants of estrogen synthesis in postmenopausal women and are the
      most effective endocrine treatments for hormone receptor positive breast cancer
      in such women. Little is known of the molecular effects of these agents on human
      breast carcinomas in vivo. METHODS: We randomly assigned primary estrogen
      receptor positive breast cancer patients to treatment with anastrozole or
      letrozole for 2 weeks before surgery. Expression profiling using cDNA arrays was
      conducted on pretreatment and post-treatment biopsies. Sample pairs from 34
      patients provided sufficient RNA for analysis. RESULTS: Profound changes in gene
      expression were seen with both aromatase inhibitors, including many classical
      estrogen-dependent genes such as TFF1, CCND1, PDZK1 and AGR2, but also many other
      genes that are likely to represent secondary responses; decrease in the
      expression of proliferation-related genes were particularly prominent. Many
      upregulated genes are involved in extracellular matrix remodelling, including
      collagens and members of the small leucine-rich proteoglycan family (LUM, DCN,
      and ASPN). No significant differences were seen between letrozole and anastrozole
      in terms of molecular effects. The gene changes were integrated into a Global
      Index of Dependence on Estrogen (GIDE), which enumerates the genes changing by at
      least twofold with therapy. The GIDE varied markedly between tumours and related
      significantly to pretreatment levels of HER2 and changes in immunohistochemically
      detected Ki67. CONCLUSION: Our findings identify the transcriptional signatures
      associated with aromatase inhibitor treatment of primary breast tumours. Larger
      datasets using this approach should enable identification of estrogen-dependent
      molecular changes, which are the determinants of benefit or resistance to
      endocrine therapy.

PMID- 17555562
TI  - Relationship between redox activity and chemical speciation of size-fractionated
      particulate matter.
AB  - BACKGROUND: Although the mechanisms of airborne particulate matter (PM) related
      health effects remain incompletely understood, one emerging hypothesis is that
      these adverse effects derive from oxidative stress, initiated by the formation of
      reactive oxygen species (ROS) within affected cells. Typically, ROS are formed in
      cells through the reduction of oxygen by biological reducing agents, with the
      catalytic assistance of electron transfer enzymes and redox active chemical
      species such as redox active organic chemicals and metals. The purpose of this
      study was to relate the electron transfer ability, or redox activity, of the PM
      samples to their content in polycyclic aromatic hydrocarbons and various
      inorganic species. The redox activity of the samples has been shown to correlate
      with the induction of the stress protein, hemeoxygenase-1. RESULTS: Size
      fractionated (i.e. < 0.15; < 2.5 and 2.5 - 10 microm in diameter) ambient PM
      samples were collected from four different locations in the period from June 2003
      to July 2005, and were chemically analyzed for elemental and organic carbon,
      ions, elements and trace metals and polycyclic aromatic hydrocarbons. The redox
      activity of the samples was evaluated by means of the dithiothreitol activity
      assay and was related to their chemical speciation by means of correlation
      analysis. Our analysis indicated a higher redox activity on a per PM mass basis
      for ultrafine (< 0.15 microm) particles compared to those of larger sizes. The PM
      redox activity was highly correlated with the organic carbon (OC) content of PM
      as well as the mass fractions of species such as polycyclic aromatic hydrocarbons
      (PAH), and selected metals. CONCLUSION: The results of this work demonstrate the
      utility of the dithiothreitol assay for quantitatively assessing the redox
      potential of airborne particulate matter from a wide range of sources. Studies to
      characterize the redox activity of PM from various sources throughout the Los
      Angeles basin are currently underway.

PMID- 17555563
TI  - Characterization of a small PlcR-regulated gene co-expressed with cereolysin O.
AB  - BACKGROUND: In the human pathogen Bacillus cereus, the expression of most
      extracellular virulence factors is controlled by the transcriptional activator
      PlcR. Among these virulence factors, cereolysin O (Clo) is an haemolysin
      belonging to the cholesterol-dependant cytolysins, a protein family extensively
      studied in Gram-positive bacteria. RESULTS: In the genomes of bacteria belonging
      to the B. cereus group, including Bacillus anthracis and Bacillus thuringiensis,
      a small gene encoding a 26-amino acid peptide was present in multicopy. One copy
      was always found upstream from the gene encoding Clo. In B. cereus ATCC 14579,
      the small gene and the clo gene are co-transcribed. Transcriptional fusions
      showed that the three paralogues identified in this strain were expressed in a
      PlcR-dependent manner. We propose to name these peptides Spp for small PlcR
      regulated peptides. We show that a synthetic peptide corresponding to the deduced
      product of the spp genes displayed antibacterial activity. CONCLUSION: The co
      expression of spp, a small PlcR-regulated multicopy gene with clo suggests a yet
      unidentified relationship between Spp and the cholesterol-dependent cytolysin in
      bacteria belonging to the B.cereus group.

PMID- 17555565
TI  - Silent cerebral infarct after cardiac catheterization as detected by diffusion
      weighted Magnetic Resonance Imaging: a randomized comparison of radial and
      femoral arterial approaches.
AB  - BACKGROUND AND OBJECTIVE: Cerebral microembolism detected by transcranial Doppler
      (TCD) occurs systematically during cardiac catheterization, but its clinical
      relevance, remains unknown. Studies suggest that asymptomatic embolic cerebral
      infarction detectable by diffusion-weighted (DW) MRI might exist after
      percutaneous cardiac interventions with a frequency as high as 15 to 22% of
      cases. We have set up, for the first time, a prospective multicenter trial to
      assess the rate of silent cerebral infarction after cardiac catheterization and
      to compare the impact of the arterial access site, comparing radial and femoral
      access, on this phenomenon. STUDY DESIGN: This prospective study will be
      performed in patients with severe aortic valve stenosis. To assess the occurrence
      of cerebral infarction, all patients will undergo cerebral DW-MRI and
      neurological assessment within 24 hours before, and 48 hours after cardiac
      catheterization and retrograde catheterization of the aortic valve. Randomization
      for the access site will be performed before coronary angiography. A subgroup
      will be monitored by transcranial power M-mode Doppler during cardiac
      catheterization to observe cerebral blood flow and track emboli.
      Neuropsychological tests will also be recorded in a subgroup of patients before
      and after the interventional procedures to assess the impact of silent brain
      injury on potential cognitive decline. The primary end-point of the study is a
      direct comparison of ischemic cerebral lesions as detected by serial cerebral DW
      MRI between patients explored by radial access and patients explored by femoral
      access. Secondary end-points include comparison of neuropsychological test
      performance and number of microembolism signals observed in the two groups.
      IMPLICATIONS: Using serial DW-MRI, silent cerebral infarction rate will be
      defined and the potential influence of vascular access site will be evaluated.
      Silent cerebral infarction might be a major concern during cardiac
      catheterization and its potential relationship to cognitive decline needs to be
      assessed. STUDY REGISTRATION: The SCIPION study is registered through National
      Institutes of Health-sponsored clinical trials registry and has been assigned the
      Identifier: NCT 00329979.

PMID- 17555564
TI  - Healthcare utilization of patients accessing an African national treatment
      program.
AB  - BACKGROUND: The roll-out of antiretroviral therapy (ART) in Africa will have
      significant resource implications arising from its impact on demand for
      healthcare services. Existing studies of healthcare utilization on HAART have
      been conducted in the developed world, where HAART is commenced when HIV illness
      is less advanced. METHODS: This paper describes healthcare utilization from
      program entry by treatment-naive patients in a peri-urban settlement in South
      Africa. Treatment criteria included a CD4 cell count <200 cells/microl or an AIDS
      defining illness. Data on health service utilization were collected
      retrospectively from the primary-care clinic and secondary and tertiary referral
      hospitals. Hospital visits were reviewed to determine the clinical reason for
      each visit. RESULTS: 212 patients were followed for a median of 490 days.
      Outpatient visits per 100 patient years of observation (PYO), excluding scheduled
      primary-care follow-up, fell from 596 immediately prior to ART to 334 in the
      first 48 weeks on therapy and 245 thereafter. Total inpatient time fell from
      2,549 days per 100 PYO pre-ART to 476 in the first 48 weeks on therapy and 73
      thereafter. This fall in healthcare utilization occurred at every level of care.
      The greatest causes of utilization were tuberculosis, cryptococcal meningitis,
      HIV-related neoplasms and adverse reactions to stavudine. After 48 weeks on ART
      demand reverted to primarily non-HIV-related causes. CONCLUSION: Utilization of
      both inpatient and outpatient hospital services fell significantly after
      commencement of ART for South African patients in the public sector, with
      inpatient demand falling fastest. Earlier initiation might reduce early on-ART
      utilization rates.

PMID- 17555566
TI  - Increasing number of components of the metabolic syndrome and cardiac structural
      and functional abnormalities--cross-sectional study of the general population.
AB  - BACKGROUND: We aimed to assess whether we could identify a graded association
      between increasing number of components of the metabolic syndrome and cardiac
      structural and functional abnormalities independently of predicted risk of
      coronary heart disease by the Framingham risk score. METHODS: We conducted a
      cross-sectional study on a random sample of the urban population of Porto aged 45
      years or over. Six hundred and eighty-four participants were included. Data were
      collected by a structured clinical interview with a physician, ECG and a
      transthoracic M-mode and 2D echocardiogram. The metabolic syndrome was defined
      according to ATPIII-NCEP. The association between the number of features of the
      metabolic syndrome and the cardiac structural and functional abnormalities was
      assessed by 3 multivariate regression models: adjusting for age and gender,
      adjusting for the 10-year predicted risk of coronary heart disease by Framingham
      risk score and adjusting for age, gender and systolic blood pressure. RESULTS:
      There was a positive association between the number of features of metabolic
      syndrome and parameters of cardiac structure and function, with a consistent and
      statistically significant trend for all cardiac variables considered when
      adjusting for age and gender. Parameters of left ventricular geometry patterns,
      left atrial diameter and diastolic dysfunction maintained this trend when taking
      into account the 10-year predicted risk of coronary heart disease by the
      Framingham score as an independent variable, while left ventricular systolic
      dysfunction did not. The prevalence of left ventricular diastolic dysfunction,
      and the mean left ventricular mass, left ventricular diameter and left atrial
      diameter increased significantly with the number of features of the metabolic
      syndrome when additionally adjusting for systolic blood pressure as a continuous
      variable. CONCLUSION: Increasing severity of metabolic syndrome was associated
      with increasingly compromised structure and function of the heart. This
      association was independent of Framingham risk score for indirect indices of
      diastolic dysfunction but not systolic dysfunction, and was not explained by
      blood pressure level.

PMID- 17555567
TI  - A mitogenomic approach to the taxonomy of pollocks: Theragra chalcogramma and T.
      finnmarchica represent one single species.
AB  - BACKGROUND: The walleye pollock (Theragra chalcogramma) and Norwegian pollock (T.
      finnmarchica) are confined to the North Pacific and North Atlantic Oceans,
      respectively, and considered as distinct species within the family Gadidae. We
      have determined the complete mtDNA nucleotide sequence of two specimens of
      Norwegian pollock and compared the sequences to that of 10 specimens of walleye
      pollock representing stocks from the Sea of Japan and the Bering Sea, 2 specimens
      of Atlantic cod (Gadus morhua), and 2 specimens of haddock (Melanogrammus
      aeglefinus). RESULTS: A total number of 204 variable positions were identified
      among the 12 pollock specimens, but no specific substitution pattern could be
      identified between the walleye and Norwegian pollocks. Phylogenetic analysis
      using 16,500 homologous mtDNA nucleotide positions clearly identify the Norwegian
      pollock within the walleye pollock species cluster. Furthermore, the Norwegian
      pollock sequences were most similar to mitochondrial genotypes present in walleye
      pollock specimens from the Sea of Japan, an observation supported both by
      neighbor-joining, maximum parsimony, and maximum likelihood analyses. CONCLUSION:
      We infer that walleye pollock and Norwegian pollock represent one single species
      and that Norwegian pollock has been recently introduced from the Pacific to the
      Atlantic Oceans.

PMID- 17555568
TI  - Preservation of proliferating pancreatic progenitor cells by Delta-Notch
      signaling in the embryonic chicken pancreas.
AB  - BACKGROUND: Genetic studies have shown that formation of pancreatic endocrine
      cells in mice is dependent on the cell autonomous action of the bHLH
      transcription factor Neurogenin3 and that the extent and timing of endocrine
      differentiation is controlled by Notch signaling. To further understand the
      mechanism by which Notch exerts this function, we have investigated pancreatic
      endocrine development in chicken embryos. RESULTS: In situ hybridization showed
      that expression of Notch signaling components and pro-endocrine bHLH factors is
      conserved to a large degree between chicken and mouse. Cell autonomous inhibition
      of Notch signal reception results in significantly increased endocrine
      differentiation demonstrating that these early progenitors are prevented from
      differentiating by ongoing Notch signaling. Conversely, activated Notch1 induces
      Hes5-1 expression and prevents endocrine development. Notably, activated Notch
      also prevents Ngn3-mediated induction of a number of downstream targets including
      NeuroD, Hes6-1, and MyT1 suggesting that Notch may act to inhibit both Ngn3 gene
      expression and protein function. Activated Notch1 could also block endocrine
      development and gene expression induced by NeuroD. Nevertheless, Ngn3- and NeuroD
      induced delamination of endodermal cells was insensitive to activated Notch under
      these conditions. Finally, we show that Myt1 can partially overcome the
      repressive effect of activated Notch on endocrine gene expression. CONCLUSION: We
      conclude that pancreatic endocrine development in the chicken relies on a
      conserved bHLH cascade under inhibitory control of Notch signaling. This lays the
      ground for further studies that take advantage of the ease at which chicken
      embryos can be manipulated. Our results also demonstrate that Notch can repress
      Ngn3 and NeuroD protein function and stimulate progenitor proliferation. To
      determine whether Notch in fact does act in Ngn3-expressing cells in vivo will
      require further studies relying on conditional mutagenesis. Lastly, our results
      demonstrate that expression of differentiation markers can be uncoupled from the
      process of delamination of differentiating cells from the epithelium.

PMID- 17555569
TI  - Directional responses following recombinant cytokine stimulation of rainbow trout
      (Oncorhynchus mykiss) RTS-11 macrophage cells as revealed by transcriptome
      profiling.
AB  - BACKGROUND: The early stages of the immune response are regulated by key
      cytokines including both interleukin 1beta (IL-1beta) and interferon-gamma (IFN
      gamma) which stimulate panels of responsive genes via conserved signal
      transduction pathways. To further our understanding of the transcriptional
      response to these cytokines in lower vertebrates we have utilized microarray
      analysis to characterize the transcriptional response to recombinant rainbow
      trout IL-1beta and IFN-gamma in the trout macrophage cell line RTS-11. RESULTS:
      RNA was extracted from stimulated or control cells following 6 h incubation and
      used to hybridize to a salmonid cDNA microarray containing 16,006 different
      genes. Analysis of the arrays revealed mRNA transcripts that were differentially
      expressed as a result of exposure to the recombinant proteins, with some
      responses common for both cytokines. In general the recombinant IL-1beta elicited
      a response where genes involved in the acute phase response were up-regulated,
      whilst the recombinant IFN-gamma induced strong up-regulation of genes involved
      in the MHC class I antigen presentation pathway. Key genes were chosen that were
      differentially regulated and analysed by real time PCR at additional time points,
      up to 48 h following stimulation. This allowed a deeper insight into the kinetics
      of the response to the cytokines in this cell line. CONCLUSION: We demonstrated
      that in fish both rIL-1beta and rIFN-gamma stimulated discrete panels of mRNA
      transcripts which indicted the cells were being directed towards different
      cellular functions, with IL-beta inducing genes involved in the inflammatory
      response, whereas IFN-gamma induced genes associated with antigen presentation.

PMID- 17555570
TI  - Microbial larvicides for malaria control in The Gambia.
AB  - BACKGROUND: Mosquito larval control may prove to be an effective tool for
      incorporating into integrated vector management (IVM) strategies for reducing
      malaria transmission. Here the efficacy of microbial larvicides against Anopheles
      gambiae s.l. was tested in preparation for a large-scale larviciding programme in
      The Gambia. METHODS: The impact of water-dispersible (WDG) and corn granule (CG)
      formulations of commercial Bacillus sphaericus strain 2362 (Bs; VectoLex) and
      Bacillus thuringiensis var.israelensis strain AM65-52 (Bti; VectoBac) on larval
      development were tested under laboratory and field conditions to (1) identify the
      susceptibility of local vectors, (2) evaluate the residual effect and re
      treatment intervals, (3) test the effectiveness of the microbials under
      operational application conditions and (4) develop a method for large-scale
      application. RESULTS: The major malaria vectors were highly susceptible to both
      microbials. The lethal concentration (LC) to kill 95% of third instar larvae of
      Anopheles gambiae s.s. after 24 hours was 0.023 mg/l (14.9 BsITU/l) for Bs WDG
      and 0.132 mg/l (396 ITU/l) for Bti WDG. In general Bs had little residual effect
      under field conditions even when the application rate was 200 times greater than
      the LC95. However, there was a residual effect up to 10 days in standardized
      field tests implemented during the dry season. Both microbials achieved 100%
      mortality of larvae 24-48 hours post-application but late instar larvae were
      detected 4 days after treatment. Pupae development was reduced by 94% (95%
      Confidence Interval = 90.8-97.5%) at weekly re-treatment intervals. Field tests
      showed that Bs had no residual activity against anopheline larvae. Both
      microbials provided complete protection when applied weekly. The basic training
      of personnel in identification of habitats, calibration of application equipment
      and active larviciding proved to be successful and achieved full coverage and
      control of mosquito larvae for three months under fully operational conditions.
      CONCLUSION: Environmentally safe microbial larvicides can significantly reduce
      larval abundance in the natural habitats of The Gambia and could be a useful tool
      for inclusion in an IVM programme. The costs of the intervention in this setting
      could be reduced with formulations that provide a greater residual effect.

PMID- 17555571
TI  - Rejection of large HPV-16 expressing tumors in aged mice by a single immunization
      of VacciMax encapsulated CTL/T helper peptides.
AB  - The incidence of cancer increases significantly in later life, yet few pre
      clinical studies of cancer immunotherapy use mice of advanced age. A novel
      vaccine delivery platform (VacciMax,VM) is described that encapsulates antigens
      and adjuvants in multilamellar liposomes in a water-in-oil emulsion. The
      therapeutic potential of VM-based vaccines administered as a single dose was
      tested in HLA-A2 transgenic mice of advanced age (48-58 weeks old) bearing large
      palpable TC1/A2 tumors. The VM-based vaccines contained one or more peptides
      having human CTL epitopes derived from HPV 16 E6 and E7. VM formulations
      contained a single peptide, a mixture of four peptides or the same four peptides
      linked together in a single long peptide. All VM formulations contained PADRE and
      CpG as adjuvants and ISA51 as the hydrophobic component of the water-in-oil
      emulsion. VM-formulated vaccines containing the four peptides as a mixture or
      linked together in one long peptide eradicated 19-day old established tumors
      within 21 days of immunization. Peptide-specific cytotoxic cellular responses
      were confirmed by ELISPOT and intracellular staining for IFN-gamma producing CD8+
      T cells. Mice rendered tumor-free by vaccination were re-challenged in the
      opposite flank with 10 million HLF-16 tumor cells, another HLA-A2/E6/E7
      expressing tumor cell line. None of these mice developed tumors following the re
      challenge. In summary, this report describes a VM-formulated therapeutic vaccine
      with the following unprecedented outcome: a) eradication of large tumors (> 700
      mm3) b) in mice of advanced age c) in less than three weeks post-immunization d)
      following a single vaccination.

PMID- 17555572
TI  - Traditional knowledge of wild edible plants used in the northwest of the Iberian
      Peninsula (Spain and Portugal): a comparative study.
AB  - BACKGROUND: We compare traditional knowledge and use of wild edible plants in six
      rural regions of the northwest of the Iberian Peninsula as follows: Campoo, Picos
      de Europa, Pilona, Sanabria and Caurel in Spain and Parque Natural de Montesinho
      in Portugal. METHODS: Data on the use of 97 species were collected through
      informed consent semi-structured interviews with local informants. A semi
      quantitative approach was used to document the relative importance of each
      species and to indicate differences in selection criteria for consuming wild food
      species in the regions studied. RESULTS AND DISCUSSION: The most significant
      species include many wild berries and nuts (e.g. Castanea sativa, Rubus
      ulmifolius, Fragaria vesca) and the most popular species in each food-category
      (e.g. fruits or herbs used to prepare liqueurs such as Prunus spinosa, vegetables
      such as Rumex acetosa, condiments such as Origanum vulgare, or plants used to
      prepare herbal teas such as Chamaemelum nobile). The most important species in
      the study area as a whole are consumed at five or all six of the survey sites.
      CONCLUSION: Social, economic and cultural factors, such as poor communications,
      fads and direct contact with nature in everyday life should be taken into account
      in determining why some wild foods and traditional vegetables have been consumed,
      but others not. They may be even more important than biological factors such as
      richness and abundance of wild edible flora. Although most are no longer
      consumed, demand is growing for those regarded as local specialties that reflect
      regional identity.

PMID- 17555573
TI  - 'I just keep thinking I haven't got it because I'm not yellow': a qualitative
      study of the factors that influence the uptake of Hepatitis C testing by
      prisoners.
AB  - BACKGROUND: Hepatitis C viral (HCV) infection is a significant public health
      problem. In the UK, an estimated 200,000 individuals have active HCV infection,
      most of whom are injecting drug users (IDUs). Many IDUs spend time within the
      prison system therefore screening for HCV infection in this setting is important.
      However, uptake of testing within prisons is very low. METHODS: Qualitative
      interview study. 30 interviews with 25 male and 5 female prisoners with a history
      of injecting drug use. RESULTS: Personal and institutional barriers to uptake of
      testing for HCV were identified. Personal barriers included: prisoners' fears and
      lack of knowledge about HCV, low motivation for testing, lack of awareness about
      the testing procedure, and concerns about confidentiality and stigma.
      Institutional barriers included: the prisons' applications procedure for testing,
      inadequate pre- and post-test discussion, lack of pro-active approaches to
      offering testing, and lack of continuity of care on discharge and transfer.
      CONCLUSION: This study highlights potential areas of development in the
      management of HCV in prisons. Further research is needed to evaluate care
      pathways for HCV in the prison setting and to develop and assess interventions to
      improve the uptake of testing for HCV by prisoners.

PMID- 17555575
TI  - Nurses' experiences of recruitment and migration from developing countries: a
      phenomenological approach.
AB  - BACKGROUND: There is growing concern globally at the current flows of nurse
      migration, particularly from low-income to middle and high-income countries.
      Recruitment practices of many countries such as Ireland are thought to be
      fuelling this rate of migration. This paper aims to establish the perceptions and
      opinions of those involved in the recruitment process on their role in
      recruitment and the effects recruitment has on both source and destination
      countries. METHODS: A purposive sample of 12 directors of nursing, from major
      academic teaching hospitals in Dublin and hospitals in South Africa and the
      Philippines were recruited. Ten overseas nurses were also recruited. A
      phenomenological approach was used with semi-structured interviews as the data
      collection method. RESULTS: There were pronounced differences in opinions between
      the Irish and the overseas directors on recruitment and its effects on the health
      systems of the source countries. Difficulties in the retention of staff were
      highlighted by both groups of directors. Other findings included the language and
      cultural differences experienced by the overseas nurses. CONCLUSION: Recruitment
      of overseas nurses should not be left to the individual employer even in the
      presence of government guidelines. An international effort from all the involved
      parties is required to formulate a solution to this complex issue in order to
      protect both the health systems of individual countries and the nurse's right to
      migrate.

PMID- 17555574
TI  - Molecular phylogeny of the Drosophila obscura species group, with emphasis on the
      Old World species.
AB  - BACKGROUND: Species of the Drosophila obscura species group (e.g., D.
      pseudoobscura, D. subobscura) have served as favorable models in evolutionary
      studies since the 1930's. Despite numbers of studies conducted with varied types
      of data, the basal phylogeny in this group is still controversial, presumably
      owing to not only the hypothetical 'rapid radiation' history of this group, but
      also limited taxon sampling from the Old World (esp. the Oriental and
      Afrotropical regions). Here we reconstruct the phylogeny of this group by using
      sequence data from 6 loci of 21 species (including 16 Old World ones) covering
      all the 6 subgroups of this group, estimate the divergence times among lineages,
      and statistically test the 'rapid radiation' hypothesis. RESULTS: Phylogenetic
      analyses indicate that each of the subobscura, sinobscura, affinis, and
      pseudoobscura subgroups is monophyletic. The subobscura and microlabis subgroups
      form the basal clade in the obscura group. Partial species of the obscura
      subgroup (the D. ambigua/D. obscura/D. tristis triad plus the D. subsilvestris/D.
      dianensis pair) forms a monophyletic group which appears to be most closely
      related to the sinobscura subgroup. The remaining basal relationships in the
      obscura group are not resolved by the present study. Divergence times on a ML
      tree based on mtDNA data are estimated with a calibration of 30-35 Mya for the
      divergence between the obscura and melanogaster groups. The result suggests that
      at least half of the current major lineages of the obscura group originated by
      the mid-Miocene time (~15 Mya), a time of the last developing and fragmentation
      of the temperate forest in North Hemisphere. CONCLUSION: The obscura group began
      to diversify rapidly before invading into the New World. The subobscura and
      microlabis subgroups form the basal clade in this group. The obscura subgroup is
      paraphyletic. Partial members of this subgroup (D. ambigua, D. obscura, D.
      tristis, D. subsilvestris, and D. dianensis) form a monophyletic group which
      appears to be most closely related to the sinobscura subgroup.

PMID- 17555576
TI  - Comparative temporal and dose-dependent morphological and transcriptional uterine
      effects elicited by tamoxifen and ethynylestradiol in immature, ovariectomized
      mice.
AB  - BACKGROUND: Uterine temporal and dose-dependent histopathologic, morphometric and
      gene expression responses to the selective estrogen receptor modulator tamoxifen
      (TAM) were comprehensively examined to further elucidate its estrogen receptor
      mediated effects. These results were systematically compared to the effects
      elicited by the potent estrogen receptor ligand 17alpha-ethynylestradiol (EE) to
      identify pathways similarly and uniquely modified by each compound. RESULTS:
      Three daily doses of 100 microg/kg TAM elicited a dose-dependent increase in
      uterine wet weight (UWW) in immature, ovariectomized C57BL/6 mice at 72 hrs with
      concurrent increases in luminal epithelial cell height (LECH), luminal
      circumference and glandular epithelial tubule number. Significant UWW and LECH
      increases were detected at 24 hrs after a single dose of 100 microg/kg TAM. cDNA
      microarray analysis identified 2235 differentially expressed genes following a
      single dose of 100 microg/kg TAM at 2, 4, 8, 12, 18 and 24 hrs, and at 72 hrs
      after three daily doses (3 x 24 hrs). Functional annotation of differentially
      expressed genes was associated with cell growth and proliferation, cytoskeletal
      organization, extracellular matrix modification, nucleotide synthesis, DNA
      replication, protein synthesis and turnover, lipid metabolism, glycolysis and
      immunological responses as is expected from the uterotrophic response.
      Comparative analysis of TAM and EE treatments identified 1209 common,
      differentially expressed genes, the majority of which exhibited similar profiles
      despite a temporal delay in TAM elicited responses. However, several conserved
      and treatment specific responses were identified that are consistent with
      proliferation (Fos, Cdkn1a, Anapc1), and water imbibition (Slc30a3, Slc30a5)
      responses elicited by EE. CONCLUSION: Overall, TAM and EE share similar gene
      expression profiles. However, TAM responses exhibit lower efficacy, while
      responses unique to EE are consistent with the physiological differences elicited
      between compounds.

PMID- 17555577
TI  - FDG-PET scan in patients with clinically and/or radiologically suspicious
      colorectal cancer recurrence but normal CEA.
AB  - BACKGROUND: Although frequently used for tumor surveillance, the sensitivity of
      carcinoembryonic antigen (CEA) to detect recurrent colorectal cancer (CRC) is not
      optimal. Fluorine 18-fluoro-2-deoxy-glucose-positron emission tomography (18F FDG
      PET) scans promise to improve recurrent CRC detection. We aimed to review PET
      scans of patients with clinically and/or radiologically suspicious tumor
      recurrence but normal CEA. METHODS: A retrospective review of an electronic
      database of 308 patients with CRC who had PET scans was performed. Only PET
      studies of patients with normal CEAs and suspected tumor recurrence who had
      pathological verification were selected for further analysis. Thirty-nine
      patients met the inclusion criteria. RESULTS: PET was positive in 26 patients
      (67%) and normal in 13 (33%). Histopathologic evidence of tumor recurrence was
      seen in 27 of the 39 patients (69%). When correlated with histopathology, PET was
      true positive in 22 patients, false positive in 4, true negative in 8 and false
      negative in 5. Overall, the accuracy of PET was 76.9%, negative predictive value
      (NPV) was 61.5%, and positive predictive value (PPV) was 84.6%. PPV value of PET
      for liver metastases was 88.8% compared to 73.3% for local recurrence. In two
      patients with confirmed recurrence, CEA became positive 2 months after PET scan
      indicating earlier detection of disease with PET. The false positive PET findings
      were mainly in the bowel and were secondary to acute/chronic inflammation and
      granulation tissue. In 3 patients with false negative PET, histopathology was
      consistent with mucinous adenocarcinoma. CONCLUSION: PET yields high PPV for
      recurrent CRC, particularly for liver metastases, in spite of normal CEA levels
      and should be considered early in the evaluation of patients with suspected tumor
      recurrence.

PMID- 17555578
TI  - Age-related waning of in vitro Interferon-gamma levels against r32kDaBCG in BCG
      vaccinated children.
AB  - BACKGROUND: Mycobacterium bovis BCG vaccine has displayed inconsistent efficacy
      in different trials conducted in various geographical regions. Nevertheless, it
      significantly reduces the risk of severe childhood tuberculosis and continues to
      be used to prevent tuberculosis in many countries. Many studies revealed that
      efficacy of vaccine wanes with age. Most of the studies were based on in vivo and
      in vitro responses to tuberculin. With the advent of newer tests such as in vitro
      interferon-gamma assays and identification of potent immunogenic mycobacterial
      proteins there is a need to corroborate the observations. This study aims at
      ascertaining the need for a booster at a later age as indicated by in vitro
      release of IFN-gamma while evaluating Ag85A as an antigen. METHODS: Ninety
      healthy children who were without any clinical evidence of the disease, 45 with a
      BCG-scar and the remaining 45 without scar and 25 with tuberculosis were included
      in the study. The incidence of TB was analyzed in 216 children attending a DOTS
      clinic during 1996-2005. CD3+, CD4+ and CD8+ cell counts were measured by Flow
      cytometry. r32kDaBCG (Ag85A-BCG) protein was used to stimulate T cells in in
      vitro T cell responses and interferon-gamma (IFN-gamma) cytokine levels in the
      supernatants were measured by ELISA. RESULTS: High incidence of TB was observed
      in age group 13-14 years followed by children in the age group 10-12 years (Chi
      square 242.22; p < 0.000). T cell subsets were within the normal range in all
      subjects. 79% of vaccinated children showed positive proliferative responses with
      a mean SI value of 4.98 +/- 1.99 while only 39% of the unvaccinated and 58% of
      the tuberculosis children showed positive responses with mean values of 2.9 +/-
      1.6 (p < 0.001) and 2.9 +/- 1.7(p < 0.057), respectively. The stimulation indices
      in vaccinated children decreased in the older children concurring with an
      increase in the incidence of TB. CONCLUSION: Significantly high levels of in
      vitro IFN-gamma demonstrated in BCG vaccinated children in our study substantiate
      the observation that BCG is effective in children, but the effect may wane with
      age. The immunity could be boosted using modified r32kDa (Ag85A) of BCG.

PMID- 17555579
TI  - Assessment and risk reduction of infectious pathogens on chiropractic treatment
      tables.
AB  - BACKGROUND: To investigate the presence of pathogenic microbes on chiropractic
      treatment tables in one outpatient teaching clinic. Additional aims were to test
      inexpensive disinfectants on tables that may kill microbes and suggest infection
      control measures for chiropractic offices, clinics and classrooms. The aim of the
      study was to assess the presence of pathogenic microbes on treatment tables in
      one outpatient teaching clinic and determine a simple behavioral model for
      infection control including table disinfection and accepted hand washing and
      sanitizing protocols. METHODS: 10 treatment tables were selected and sampled for
      possible microbial flora on face and hand pieces. Samples were cultured on
      MacConky's agar and mannitol salt agar, labeled and incubated for up to 48 hours.
      Confirmatory testing of microbes to determine if drug resistant flora were
      present was performed. Among tables tested, 5 were selected to test
      disinfectants. One-half of the face piece and 1 hand piece were treated with two
      different wipes and then post-tested for microbes. RESULTS: Pathogenic microbes
      were present on chiropractic treatment tables including methicillin-resistant
      Staph aureus. Simple disinfectants neutralized the pathogens. A rudimentary
      disinfection procedure and infection control measures are suggested based on the
      findings. CONCLUSION: Pathogenic microbes may be present on chiropractic
      treatment tables and can be effectively killed with proper disinfecting. Hand
      washing/sanitizing is an important measure in infection control as is table
      disinfecting. Rudimentary behavioral changes to improve chiropractic clinic
      infection control are needed. More comprehensive behavioral models are needed.
      All teaching clinics and private chiropractic offices should adopt infection
      control practices including routine table disinfecting and hand sanitizing.
      Effective measures can be put in place at minimal costs. Accrediting bodies of
      chiropractic institutions should mandate an infection control plan for member
      institutions immediately.

PMID- 17555580
TI  - Cyclooxygenase activity is important for efficient replication of mouse hepatitis
      virus at an early stage of infection.
AB  - Cyclooxygenases (COXs) play a significant role in many different viral infections
      with respect to replication and pathogenesis. Here we investigated the role of
      COXs in the mouse hepatitis coronavirus (MHV) infection cycle. Blocking COX
      activity by different inhibitors or by RNA interference affected MHV infection in
      different cells. The COX inhibitors reduced MHV infection at a post-binding step,
      but early in the replication cycle. Both viral RNA and viral protein synthesis
      were affected with subsequent loss of progeny virus production. Thus, COX
      activity appears to be required for efficient MHV replication, providing a
      potential target for anti-coronaviral therapy.

PMID- 17555581
TI  - Fibromuscular dysplasia.
AB  - Fibromuscular dysplasia (FMD), formerly called fibromuscular fibroplasia, is a
      group of nonatherosclerotic, noninflammatory arterial diseases that most commonly
      involve the renal and carotid arteries. The prevalence of symptomatic renal
      artery FMD is about 4/1000 and the prevalence of cervicocranial FMD is probably
      half that. Histological classification discriminates three main subtypes,
      intimal, medial and perimedial, which may be associated in a single patient.
      Angiographic classification includes the multifocal type, with multiple stenoses
      and the 'string-of-beads' appearance that is related to medial FMD, and tubular
      and focal types, which are not clearly related to specific histological lesions.
      Renovascular hypertension is the most common manifestation of renal artery FMD.
      Multifocal stenoses with the 'string-of-beads' appearance are observed at
      angiography in more than 80% of cases, mostly in women aged between 30 and 50
      years; they generally involve the middle and distal two-thirds of the main renal
      artery and in some case also renal artery branches. Cervicocranial FMD can be
      complicated by dissection with headache, Horner's syndrome or stroke, or can be
      associated with intracerebral aneurysms with a risk of subarachnoid or
      intracerebral hemorrhage. The etiology of FMD is unknown, although various
      hormonal and mechanical factors have been suggested. Subclinical lesions are
      found at arterial sites distant from the stenotic arteries, and this suggests
      that FMD is a systemic arterial disease. It appears to be familial in 10% of
      cases. Noninvasive diagnostic tests include, in increasing order of accuracy,
      ultrasonography, magnetic resonance angiography and computed tomography
      angiography. The gold standard for diagnosing FMD is catheter angiography, but
      this invasive procedure is only used for patients in whom it is clinically
      pertinent to proceed with revascularization during the same procedure.
      Differential diagnosis include atherosclerotic stenoses and stenoses associated
      with vascular Ehlers-Danlos and Williams' syndromes, and type 1
      neurofibromatosis. Management of cases with renovascular hypertension includes
      antihypertensive therapy, percutaneous angioplasty of severe stenoses, and
      reconstructive surgery in cases with complex FMD that extends to segmental
      arteries. The therapeutic options for securing ruptured intracerebral aneurysms
      are microvascular neurosurgical clipping and endovascular coiling. Stenosis
      progression in renal artery FMD is slow and rarely leads to ischemic renal
      failure.

PMID- 17555582
TI  - Practical methods for incorporating summary time-to-event data into meta
      analysis.
AB  - BACKGROUND: In systematic reviews and meta-analyses, time-to-event outcomes are
      most appropriately analysed using hazard ratios (HRs). In the absence of
      individual patient data (IPD), methods are available to obtain HRs and/or
      associated statistics by carefully manipulating published or other summary data.
      Awareness and adoption of these methods is somewhat limited, perhaps because they
      are published in the statistical literature using statistical notation. METHODS:
      This paper aims to 'translate' the methods for estimating a HR and associated
      statistics from published time-to-event-analyses into less statistical and more
      practical guidance and provide a corresponding, easy-to-use calculations
      spreadsheet, to facilitate the computational aspects. RESULTS: A wider audience
      should be able to understand published time-to-event data in individual trial
      reports and use it more appropriately in meta-analysis. When faced with
      particular circumstances, readers can refer to the relevant sections of the
      paper. The spreadsheet can be used to assist them in carrying out the
      calculations. CONCLUSION: The methods cannot circumvent the potential biases
      associated with relying on published data for systematic reviews and meta
      analysis. However, this practical guide should improve the quality of the
      analysis and subsequent interpretation of systematic reviews and meta-analyses
      that include time-to-event outcomes.

PMID- 17555583
TI  - Low major histocompatibility complex class II DQA diversity in the Giant Panda
      (Ailuropoda melanoleuca).
AB  - BACKGROUND: The giant panda (Ailuropoda melanoleuca) is one of the most
      endangered animals due to habitat fragmentation and loss. Although the captive
      breeding program for this species is now nearly two decades old, researches on
      the genetic background of such captive populations, especially on adaptive
      molecular polymorphism of major histocompatibility complex (MHC), are still
      limited. In this study, we characterized adaptive variation of the giant panda's
      MHC DQA gene by PCR amplification of its antigen-recognizing region (i.e. the
      exon 2) and subsequent single-strand conformational polymorphism (SSCP) and
      sequence analyses. RESULTS: The results revealed a low level of DQA exon 2
      diversity in this rare animal, presenting 6 alleles from 61 giant panda
      individuals. The observed polymorphism was restricted to 9 amino acid
      substitutions, all of which occurred at and adjacent to positions forming the
      functionally important antigen-binding sites. All the samples were in Hardy
      Weinberg proportions. A significantly higher rate of non-synonymous than
      synonymous substitutions at the antigen-binding sites indicated positive
      selection for diversity in the locus. CONCLUSION: The DQA allelic diversity of
      giant pandas was low relative to other vertebrates. Nonetheless, the pandas
      exhibited more alleles in DQA than those in DRB, suggesting the alpha chain genes
      would play a leading role when coping with certain pathogens and thus should be
      included in conservation genetic investigation. The microsatellite and MHC loci
      might predict long-term persistence potential and short-term survival ability,
      respectively. Consequently, it is recommended to utilize multiple suites of
      microsatellite markers and multiple MHC loci to detect overall genetic variation
      in order to design unbiased conservation strategies.

PMID- 17555584
TI  - Spatial preferences of microRNA targets in 3' untranslated regions.
AB  - BACKGROUND: MicroRNAs are an important class of regulatory RNAs which repress
      animal genes by preferentially interacting with complementary sequence motifs in
      the 3' untranslated region (UTR) of target mRNAs. Computational methods have been
      developed which can successfully predict which microRNA may target which mRNA on
      a genome-wide scale. RESULTS: We address how predicted target sites may be
      affected by alternative polyadenylation events changing the 3'UTR sequence. We
      find that two thirds of targeted genes have alternative 3'UTRs, with 40% of
      predicted target sites located in alternative UTR segments. We propose three
      classes based on whether the target sites fall within constitutive and/or
      alternative UTR segments, and examine the spatial distribution of predicted
      targets in alternative UTRs. In particular, there is a strong preference for
      targets to be located in close vicinity of the stop codon and the polyadenylation
      sites. CONCLUSION: The transcript diversity seen in non-coding regions, as well
      as the relative location of miRNA target sites defined by it, has a potentially
      large impact on gene regulation by miRNAs and should be taken into account when
      defining, predicting or validating miRNA targets.

PMID- 17555585
TI  - Pulmonary congenital cystic adenomatoid malformation, type I, presenting as a
      single cyst of the middle lobe in an adult: case report.
AB  - BACKGROUND: Congenital cystic adenomatoid malformation (CCAM) of the lung is an
      uncommon fetal development anomaly of the terminal respiratory structures. The
      large cyst type usually occurs in stillborn infants or newborn infants with
      respiratory distress. Cases of CCAM have been previously described in adulthood,
      more often type I with multiloculated cystic lesions. CASE PRESENTATION: We
      report a case of type I CCAM presenting as a single, expansive cystic mass in the
      middle pulmonary lobe in a 38-year-old man, revealed by persistent cough and
      haemoptysis. Computed tomographic scan showed a single cyst with air fluid level,
      occupying the lateral segment of the lobe. When the type I CCAM is a single cyst,
      other cystic pulmonary lesions must be excluded. The intrapulmonary localization
      and the absence of cartilage in the cyst wall are conclusive findings of CCAM.
      The pathogenesis, management and differential diagnosis with other lung
      malformations are discussed along with a review of the literature. CONCLUSION:
      The literature data confirm that surgical resection is the treatment of choice in
      all cases of CCAM and in the cases of cystic pulmonary lesions with uncertain
      radiological findings, in order to perform a histological examination of the
      lesion and to prevent infection and the potential neoplastic transformation.

PMID- 17555586
TI  - Do physician outcome judgments and judgment biases contribute to inappropriate
      use of treatments? Study protocol.
AB  - BACKGROUND: There are many examples of physicians using treatments
      inappropriately, despite clear evidence about the circumstances under which the
      benefits of such treatments outweigh their harms. When such over- or under- use
      of treatments occurs for common diseases, the burden to the healthcare system and
      risks to patients can be substantial. We propose that a major contributor to
      inappropriate treatment may be how clinicians judge the likelihood of important
      treatment outcomes, and how these judgments influence their treatment decisions.
      The current study will examine the role of judged outcome probabilities and other
      cognitive factors in the context of two clinical treatment decisions: 1)
      prescription of antibiotics for sore throat, where we hypothesize overestimation
      of benefit and underestimation of harm leads to over-prescription of antibiotics;
      and 2) initiation of anticoagulation for patients with atrial fibrillation (AF),
      where we hypothesize that underestimation of benefit and overestimation of harm
      leads to under-prescription of warfarin. METHODS: For each of the two conditions,
      we will administer surveys of two types (Type 1 and Type 2) to different samples
      of Canadian physicians. The primary goal of the Type 1 survey is to assess
      physicians' perceived outcome probabilities (both good and bad outcomes) for the
      target treatment. Type 1 surveys will assess judged outcome probabilities in the
      context of a representative patient, and include questions about how physicians
      currently treat such cases, the recollection of rare or vivid outcomes, as well
      as practice and demographic details. The primary goal of the Type 2 surveys is to
      measure the specific factors that drive individual clinical judgments and
      treatment decisions, using a 'clinical judgment analysis' or 'lens modeling'
      approach. This survey will manipulate eight clinical variables across a series of
      sixteen realistic case vignettes. Based on the survey responses, we will be able
      to identify which variables have the greatest effect on physician judgments, and
      whether judgments are affected by inappropriate cues or incorrect weighting of
      appropriate cues. We will send antibiotics surveys to family physicians (300 per
      survey), and warfarin surveys to both family physicians and internal medicine
      specialists (300 per group per survey), for a total of 1,800 physicians. Each
      Type 1 survey will be two to four pages in length and take about fifteen minutes
      to complete, while each Type 2 survey will be eight to ten pages in length and
      take about thirty minutes to complete. DISCUSSION: This work will provide insight
      into the extent to which clinicians' judgments about the likelihood of important
      treatment outcomes explain inappropriate treatment decisions. This work will also
      provide information necessary for the development of an individualized feedback
      tool designed to improve treatment decisions. The techniques developed here have
      the potential to be applicable to a wide range of clinical areas where
      inappropriate utilization stems from biased judgments.

PMID- 17555587
TI  - PET probe-guided surgery: applications and clinical protocol.
AB  - INTRODUCTION: Parallel to the advances in diagnostic imaging using positron
      emission tomography (PET), and availability of new systemic treatment options,
      the treatment paradigm in oncology has shifted towards more aggressive
      therapeutic interventions to include cytoreductive techniques and
      metastasectomies. Intraoperative localization of PET positive
      recurrent/metastatic lesions can be facilitated using a hand-held PET probe.
      MATERIALS AND METHODS: Records of patients who underwent PET probe-guided surgery
      were reviewed. Surgical indications and operative targets were determined based
      on diagnostic PET/PET-CT images performed prior to probe-guided surgical
      planning. PET probe-guided surgery was performed on a separate day using a high
      energy gamma probe (PET probe, Care Wise Medical, Morgan Hills CA) 2-6 hours post
      injection of 5-15 mCi FDG. Probe count rates, target-to-background ratios, and
      lesion detection success were analyzed. RESULTS: Twenty-four patients underwent
      PET probe-guided surgery; one patient had two PET-probe guided surgeries
      resulting in a total of 25 cases (5 colorectal cancer cases, 4 thyroid cancer
      cases, 6 lymphoma cancer cases, and 10 other cancer cases). Surgical indication
      was diagnostic exploration in 6 cases with lymphoma and 1 case with head and neck
      cancer (28%). The remaining 18 cases (72%) underwent PET probe-guided surgery
      with a therapeutic intent in a recurrent or metastatic disease setting. All the
      lesions identified and targeted on a preoperative FDG-PET scan were detected by
      the PET probe with satisfactory in-vivo lesion count rates and a TBR of >/= 1.5.
      PET probe allowed localization of lesions that were non-palpable and non-obvious
      at surgical exploration in 8 patients. CONCLUSION: The use of the PET probe
      improves the success of surgical exploration in selected indications. Separate
      day protocol is clinically feasible allowing for flexible operating room
      scheduling.

PMID- 17555588
TI  - Reduction of astrogliosis and microgliosis by cerebrospinal fluid shunting in
      experimental hydrocephalus.
AB  - BACKGROUND: Reactive gliosis has the potential to alter biomechanical properties
      of the brain, impede neuronal regeneration and affect plasticity. Determining the
      onset and progression of reactive astrogliosis and microgliosis due to
      hydrocephalus is important for designing better clinical treatments. METHODS:
      Reactive astrogliosis and microgliosis were evaluated as the severity of
      hydrocephalus increased with age in hydrocephalic H-Tx rats and control
      littermates. Previous studies have suggested that gliosis may persist after short
      term drainage (shunt treatment) of the cerebrospinal fluid. Therefore shunts were
      placed in 15d hydrocephalic rats that were sacrificed after 6d (21d of age) or
      after 21d (36d of age). Tissue was processed for Western blot procedures and
      immunohistochemistry, and probed for the astrocytic protein, Glial Fibrillary
      Acidic Protein (GFAP) and for microglial protein, Isolectin B4 (ILB4). RESULTS:
      In the parietal cortex of untreated hydrocephalic animals, GFAP levels increased
      significantly at 5d and at 12d compared to age-matched control rats. There was a
      continued increase in GFAP levels over control at 21d and at 36d. Shunting
      prevented some of the increase in GFAP levels in the parietal cortex. In the
      occipital cortex of untreated hydrocephalic animals, there was a significant
      increase over control in levels of GFAP at 5d. This trend continued in the 12d
      animals, although not significantly. Significant increases in GFAP levels were
      present in 21d and in 36d animals. Shunting significantly reduced GFAP levels in
      the 36d shunted group. Quantitative grading of immuno-stained sections showed
      similar changes in GFAP stained astrocytes. Immuno-stained microglia were altered
      in shape in hydrocephalic animals. At 5d and 12d, they appeared to be
      developmentally delayed with a lack of processes. Older 21d and 36d hydrocephalic
      animals exhibited the characteristics of activated microglia, with thicker
      processes and enlarged cell bodies. Following shunting, fewer activated microglia
      were present. Histologic examination of the periventricular area and the
      periaqueductal area showed similar findings with the 21d and 36d animals having
      increased populations of both astrocytes and microglia which were reduced
      following shunting with a more dramatic reduction in the long term shunted
      animals. CONCLUSION: Overall, these results suggest that reactive astrocytosis
      and microgliosis are associated with progressive untreated ventriculomegaly, but
      that shunt treatment can reduce the gliosis occurring with hydrocephalus.

PMID- 17555589
TI  - Comparison of hybridization-based and sequencing-based gene expression
      technologies on biological replicates.
AB  - BACKGROUND: High-throughput systems for gene expression profiling have been
      developed and have matured rapidly through the past decade. Broadly, these can be
      divided into two categories: hybridization-based and sequencing-based approaches.
      With data from different technologies being accumulated, concerns and challenges
      are raised about the level of agreement across technologies. As part of an
      ongoing large-scale cross-platform data comparison framework, we report here a
      comparison based on identical samples between one-dye DNA microarray platforms
      and MPSS (Massively Parallel Signature Sequencing). RESULTS: The DNA microarray
      platforms generally provided highly correlated data, while moderate correlations
      between microarrays and MPSS were obtained. Disagreements between the two types
      of technologies can be attributed to limitations inherent to both technologies.
      The variation found between pooled biological replicates underlines the
      importance of exercising caution in identification of differential expression,
      especially for the purposes of biomarker discovery. CONCLUSION: Based on
      different principles, hybridization-based and sequencing-based technologies
      should be considered complementary to each other, rather than competitive
      alternatives for measuring gene expression, and currently, both are important
      tools for transcriptome profiling.

PMID- 17555590
TI  - Identification of sequence motifs significantly associated with antisense
      activity.
AB  - BACKGROUND: Predicting the suppression activity of antisense oligonucleotide
      sequences is the main goal of the rational design of nucleic acids. To create an
      effective predictive model, it is important to know what properties of an
      oligonucleotide sequence associate significantly with antisense activity. Also,
      for the model to be efficient we must know what properties do not associate
      significantly and can be omitted from the model. This paper will discuss the
      results of a randomization procedure to find motifs that associate significantly
      with either high or low antisense suppression activity, analysis of their
      properties, as well as the results of support vector machine modelling using
      these significant motifs as features. RESULTS: We discovered 155 motifs that
      associate significantly with high antisense suppression activity and 202 motifs
      that associate significantly with low suppression activity. The motifs range in
      length from 2 to 5 bases, contain several motifs that have been previously
      discovered as associating highly with antisense activity, and have thermodynamic
      properties consistent with previous work associating thermodynamic properties of
      sequences with their antisense activity. Statistical analysis revealed no
      correlation between a motif's position within an antisense sequence and that
      sequences antisense activity. Also, many significant motifs existed as subwords
      of other significant motifs. Support vector regression experiments indicated that
      the feature set of significant motifs increased correlation compared to all
      possible motifs as well as several subsets of the significant motifs. CONCLUSION:
      The thermodynamic properties of the significantly associated motifs support
      existing data correlating the thermodynamic properties of the antisense
      oligonucleotide with antisense efficiency, reinforcing our hypothesis that
      antisense suppression is strongly associated with probe/target thermodynamics, as
      there are no enzymatic mediators to speed the process along like the RNA Induced
      Silencing Complex (RISC) in RNAi. The independence of motif position and
      antisense activity also allows us to bypass consideration of this feature in the
      modelling process, promoting model efficiency and reducing the chance of
      overfitting when predicting antisense activity. The increase in SVR correlation
      with significant features compared to nearest-neighbour features indicates that
      thermodynamics alone is likely not the only factor in determining antisense
      efficiency.

PMID- 17555591
TI  - Impact of an in-built monitoring system on family planning performance in rural
      Bangladesh.
AB  - BACKGROUND: During 1982-1992, the Maternal and Child Health Family Planning (MCH
      FP) Extension Project (Rural) of International Centre for Diarrhoeal Disease
      Research, Bangladesh (ICDDR,B), in partnership with the Ministry of Health and
      Family Welfare (MoHFW) of the Government of Bangladesh (GoB), implemented a
      series of interventions in Sirajganj Sadar sub-district of Sirajganj district.
      These interventions were aimed at improving the planning mechanisms and for
      reviewing the problem-solving processes to build an effective monitoring system
      of the interventions at the local level of the overall system of the MOHFW, GoB.
      METHODS: The interventions included development and testing of innovative
      solutions in service-delivery, provision of door-step injectables, and
      strengthening of the management information system (MIS). The impact of an in
      built monitoring system on the overall performance was assessed during the period
      from June 1995 to December 1996, after the withdrawal of the interventions in
      1992. RESULTS: The results of the assessment showed that Family Welfare
      Assistants (FWAs) increased household-visits within the last two months, and
      there was a higher use of service-delivery points even after the withdrawal of
      the interventions. The results of the cluster surveys, conducted in 1996, showed
      that the selected indicators of health and family-planning services were higher
      than those reported by the Bangladesh Demographic and Health Survey (BDHS) 1996
      1997. During June 1995-December, 1996, the contraceptive prevalence rate (CPR)
      increased by 13 percentage points (i.e. from 40% to 53%). Compared to the
      national CPR (49%), this increase was statistically significant (p < 0.05).
      CONCLUSION: The in-built monitoring systems, including effective MIS, accompanied
      by rapid assessments and review of performance by the programme managers, have
      potentials to improve family planning performance in low-performing areas.

PMID- 17555593
TI  - 160-fold acceleration of the Smith-Waterman algorithm using a field programmable
      gate array (FPGA).
AB  - BACKGROUND: To infer homology and subsequently gene function, the Smith-Waterman
      (SW) algorithm is used to find the optimal local alignment between two sequences.
      When searching sequence databases that may contain hundreds of millions of
      sequences, this algorithm becomes computationally expensive. RESULTS: In this
      paper, we focused on accelerating the Smith-Waterman algorithm by using FPGA
      based hardware that implemented a module for computing the score of a single cell
      of the SW matrix. Then using a grid of this module, the entire SW matrix was
      computed at the speed of field propagation through the FPGA circuit. These
      modifications dramatically accelerated the algorithm's computation time by up to
      160 folds compared to a pure software implementation running on the same FPGA
      with an Altera Nios II softprocessor. CONCLUSION: This design of FPGA accelerated
      hardware offers a new promising direction to seeking computation improvement of
      genomic database searching.

PMID- 17555592
TI  - Cytokine responses of CD4+ T cells during a Plasmodium chabaudi chabaudi (ER)
      blood-stage infection in mice initiated by the natural route of infection.
AB  - BACKGROUND: Investigation of host responses to blood stages of Plasmodium spp,
      and the immunopathology associated with this phase of the life cycle are often
      performed on mice infected directly with infected red blood cells. Thus, the
      effects of mosquito bites and the pre-erythrocytic stages of the parasite, which
      would be present in natural infection, are ignored In this paper, Plasmodium
      chabaudi chabaudi infections of mice injected directly with infected red blood
      cells were compared with those of mice infected by the bites of infected
      mosquitoes, in order to determine whether the courses of primary infection and
      splenic CD4 T cell responses are similar. METHODS: C57Bl/6 mice were injected
      with red blood cells infected with P. chabaudi (ER) or infected via the bite of
      Anopheles stephensi mosquitoes. Parasitaemia were monitored by Giemsa-stained
      thin blood films. Total spleen cells, CD4+ T cells, and cytokine production (IFN
      gamma, IL-2, IL-4, IL-10) were analysed by flow cytometry. In some experiments,
      mice were subjected to bites of uninfected mosquitoes prior to infectious bites
      in order to determine whether mosquito bites per se could affect a subsequent P.
      chabaudi infection. RESULTS: P. chabaudi (ER) infections initiated by mosquito
      bite were characterized by lower parasitaemia of shorter duration than those
      observed after direct blood challenge. However, splenomegaly was comparable
      suggesting that parasitaemia alone does not account for the increase in spleen
      size. Total numbers of CD4 T cells and those producing IFN-gamma, IL-10 and IL-2
      were reduced in comparison to direct blood challenge. By contrast, the reduction
      in IL-4 producing cells was less marked suggesting that there is a proportionally
      lower Th1-like response in mice infected via infectious mosquitoes. Strikingly,
      pre-exposure to bites of uninfected mosquitoes reduced the magnitude and duration
      of the subsequent mosquito-transmitted infection still further, but enhanced the
      response of CD4 T cells producing IFN-gamma and IL-4. CONCLUSION: The data in
      this paper suggest that studying early host responses in blood stage malaria
      infections measured after direct blood challenge of mice may not completely
      reflect the natural situation, and more detailed investigations of blood-stage
      immunity after mosquito transmission in experimental models should be considered.

PMID- 17555594
TI  - Hyperglycemia regulates thioredoxin-ROS activity through induction of thioredoxin
      interacting protein (TXNIP) in metastatic breast cancer-derived cells MDA-MB-231.
AB  - BACKGROUND: We studied the RNA expression of the genes in response to glucose
      from 5 mM (condition of normoglycemia) to 20 mM (condition of
      hyperglycemia/diabetes) by microarray analysis in breast cancer derived cell line
      MDA-MB-231. We identified the thioredoxin-interacting protein (TXNIP), whose RNA
      level increased as a gene product particularly sensitive to the variation of the
      level of glucose in culture media. We investigated the kinesis of the TXNIP RNA
      and protein in response to glucose and the relationship between this protein and
      the related thioredoxin (TRX) in regulating the level of reactive oxygen species
      (ROS) in MDA-MB-231 cells. METHODS: MDA-MB-231 cells were grown either in 5 or 20
      mM glucose chronically prior to plating. For glucose shift (5/20), cells were
      plated in 5 mM glucose and shifted to 20 mM at time 0. Cells were analyzed with
      Affymetrix Human U133A microarray chip and gene expression profile was obtained.
      Semi-quantitative RT-PCR and Western blot was used to validate the expression of
      TXNIP RNA and protein in response to glucose, respectively. ROS were detected by
      CM-H2DCFDA (5-6-chloromethyl-2',7'-dichlorodihydrofluorescein diacetate) and
      measured for mean fluorescence intensity with flow cytometry. TRX activity was
      assayed by the insulin disulfide reducing assay. RESULTS: We found that the
      regulation of TXNIP gene expression by glucose in MDA-MB-231 cells occurs rapidly
      within 6 h of its increased level (20 mM glucose) and persists through the
      duration of the conditions of hyperglycemia. The increased level of TXNIP RNA is
      followed by increased level of protein that is associated with increasing levels
      of ROS and reduced TRX activity. The inhibition of the glucose transporter GLUT1
      by phloretin notably reduces TXNIP RNA level and the inhibition of the p38 MAP
      kinase activity by SB203580 reverses the effects of TXNIP on ROS-TRX activity.
      CONCLUSION: In this study we show that TXNIP is an oxidative stress responsive
      gene and its expression is exquisitely regulated by glucose level in highly
      metastatic MDA-MB-231 cells.

PMID- 17555595
TI  - An efficient pseudomedian filter for tiling microrrays.
AB  - BACKGROUND: Tiling microarrays are becoming an essential technology in the
      functional genomics toolbox. They have been applied to the tasks of novel
      transcript identification, elucidation of transcription factor binding sites,
      detection of methylated DNA and several other applications in several model
      organisms. These experiments are being conducted at increasingly finer
      resolutions as the microarray technology enjoys increasingly greater feature
      densities. The increased densities naturally lead to increased data analysis
      requirements. Specifically, the most widely employed algorithm for tiling array
      analysis involves smoothing observed signals by computing pseudomedians within
      sliding windows, a O(n2logn) calculation in each window. This poor time
      complexity is an issue for tiling array analysis and could prove to be a real
      bottleneck as tiling microarray experiments become grander in scope and finer in
      resolution. RESULTS: We therefore implemented Monahan's HLQEST algorithm that
      reduces the runtime complexity for computing the pseudomedian of n numbers to
      O(nlogn) from O(n2logn). For a representative tiling microarray dataset, this
      modification reduced the smoothing procedure's runtime by nearly 90%. We then
      leveraged the fact that elements within sliding windows remain largely unchanged
      in overlapping windows (as one slides across genomic space) to further reduce
      computation by an additional 43%. This was achieved by the application of skip
      lists to maintaining a sorted list of values from window to window. This sorted
      list could be maintained with simple O(log n) inserts and deletes. We illustrate
      the favorable scaling properties of our algorithms with both time complexity
      analysis and benchmarking on synthetic datasets. CONCLUSION: Tiling microarray
      analyses that rely upon a sliding window pseudomedian calculation can require
      many hours of computation. We have eased this requirement significantly by
      implementing efficient algorithms that scale well with genomic feature density.
      This result not only speeds the current standard analyses, but also makes
      possible ones where many iterations of the filter may be required, such as might
      be required in a bootstrap or parameter estimation setting. Source code and
      executables are available at http://tiling.gersteinlab.org/pseudomedian/.

PMID- 17555596
TI  - Repressor element-1 silencing transcription factor/neuronal restrictive silencer
      factor (REST/NRSF) can regulate HSV-1 immediate-early transcription via histone
      modification.
AB  - BACKGROUND: During primary infection of its human host, Herpes Simplex Virus Type
      1 (HSV-1) establishes latency in neurons where the viral genome is maintained in
      a circular form associated with nucleosomes in a chromatin configration. During
      latency, most viral genes are silenced, although the molecular mechanisms
      responsible for this are unclear. We hypothesized that neuronal factors repress
      HSV-1 gene expression during latency. A search of the HSV-1 DNA sequence for
      potential regulatory elements identified a Repressor Element-1/Neuronal
      Restrictive Silencer Element (RE-1/NRSE) located between HSV-1 genes ICP22 and
      ICP4. We predicted that the Repressor Element Silencing Transcription
      Factor/Neuronal Restrictive Silencer Factor (REST/NRSF) regulates expression of
      ICP22 and ICP4. RESULTS: Transient cotransfection indicated that REST/NRSF
      inhibited the activity of both promoters. In contrast, cotransfection of a mutant
      form of REST/NRSF encoding only the DNA-binding domain of the protein resulted in
      less inhibition. Stably transformed cell lines containing episomal reporter
      plasmids with a chromatin structure showed that REST/NRSF specifically inhibited
      the ICP4 promoter, but not the ICP22 promoter. REST/NRSF inhibition of the ICP4
      promoter was reversed by histone deacetylase (HDAC) inhibitor Trichostatin A
      (TSA). Additionally, chromatin immuno-precipitation (ChIP) assays indicated that
      the corepressor CoREST was recruited to the proximity of ICP4 promoter and that
      acetylation of histone H4 was reduced in the presence of REST/NRSF. CONCLUSION:
      Since the ICP4 protein is a key transactivator of HSV-1 lytic cycle genes, these
      results suggest that REST/NRSF may have an important role in the establishment
      and/or maintenance of HSV-1 gene silencing during latency by targeting ICP4
      expression.

PMID- 17555597
TI  - ZPS: visualization of recent adaptive evolution of proteins.
AB  - BACKGROUND: Detection of adaptive amino acid changes in proteins under recent
      short-term selection is of great interest for researchers studying
      microevolutionary processes in microbial pathogens or any other biological
      species. However, independent occurrence of such point mutations within
      genetically diverse haplotypes makes it difficult to detect the selection
      footprint by using traditional molecular evolutionary analyses. The recently
      developed Zonal Phylogeny (ZP) has been shown to be a useful analytic tool for
      identifying the footprints of short-term positive selection. ZP separates protein
      encoding genes into evolutionarily long-term (with silent diversity) and short
      term (without silent diversity) categories, or zones, followed by statistical
      analysis to detect signs of positive selection in the short-term zone. However,
      successful broad application of ZP for analysis of large haplotype datasets
      requires automation of the relatively labor-intensive computational process.
      RESULTS: Here we present Zonal Phylogeny Software (ZPS), an application that
      describes the distribution of single nucleotide polymorphisms (SNPs) of
      synonymous (silent) and non-synonymous (replacement) nature along branches of the
      DNA tree for any given protein-coding gene locus. Based on this information, ZPS
      separates the protein variant haplotypes with silent variability (Primary zone)
      from those that have recently evolved from the Primary zone variants by amino
      acid changes (External zone). Further comparative analysis of mutational hot-spot
      frequencies and haplotype diversity between the two zones allows determination of
      whether the External zone haplotypes emerged under positive selection.
      CONCLUSIONS: As a visualization tool, ZPS depicts the protein tree in a DNA tree,
      indicating the most parsimonious numbers of synonymous and non-synonymous changes
      along the branches of a maximum-likelihood based DNA tree, along with information
      on homoplasy, reversion and structural mutation hot-spots. Through zonal
      differentiation, ZPS allows detection of recent adaptive evolution via selection
      of advantageous structural mutations, even when the advantage conferred by such
      mutations is relatively short-term (as in the case of "source-sink" evolutionary
      dynamics, which may represent a major mode of virulence evolution in microbes).

PMID- 17555598
TI  - Alefacept (anti-CD2) causes a selective reduction in circulating effector memory
      T cells (Tem) and relative preservation of central memory T cells (Tcm) in
      psoriasis.
AB  - BACKGROUND: Alefacept (anti-CD2) biological therapy selectively targets effector
      memory T cells (Tem) in psoriasis vulgaris, a model Type 1 autoimmune disease.
      METHODS: Circulating leukocytes were phenotyped in patients receiving alefacept
      for moderate to severe psoriasis. RESULTS: In all patients, this treatment caused
      a preferential decrease in effector memory T cells (CCR7- CD45RA-) (mean 63%
      reduction) for both CD4+ and CD8+ Tem, while central memory T cells (Tcm)
      (CCR7+CD45RA-) were less affected, and naive T cells (CCR7+CD45RA+) were
      relatively spared. Circulating CD8+ effector T cells and Type 1 T cells (IFN
      gamma-producing) were also significantly reduced. CONCLUSION: Alefacept causes a
      selective reduction in circulating effector memory T cells (Tem) and relative
      preservation of central memory T cells (Tcm) in psoriasis.

PMID- 17555599
TI  - Porto-systemic shunt using adrenal vein as a conduit; an alternative procedure
      for spleno--renal shunt.
AB  - BACKGROUND: Currently, portal hypertension is still big problem for the patients
      with serious liver diseases. Variceal bleeding is one of the most important
      complications of portal hypertension. In case of failure of endoscopic and
      combined medical treatments, surgical decompressive shunts are required. We
      emphasized an alternative splenorenal shunt procedure using adrenal vein as a
      conduit. CASE PRESENTATION: A 26-year-old male suffered from recurrent variceal
      bleeding was considered for surgical therapy. Although we planned to perform a
      distal splenorenal shunt procedure, it was observed to be difficult. Therefore
      left adrenal vein was used as a conduit between left renal vein and splenic vein
      after splenic artery was ligated. He did well and was discharged from the
      hospital on the postoperative day 6. In the follow up period for nine months,
      endoscopic and ultrasonographic examinations were normal. CONCLUSION: We
      concluded that, in case of failure to perform distal splenorenal shunt due to
      technical problems, alternative porto-systemic shunt procedure using the adrenal
      vein as a vascular conduit can be safely employed.

PMID- 17555600
TI  - Single-session photodynamic therapy combined with intravitreal bevacizumab and
      triamcinolone for neovascular age-related macular degeneration.
AB  - BACKGROUND: To evaluate the efficacy of triple therapy consisting of single
      session photodynamic therapy (PDT), intravitreal bevacizumab (IVB) and
      intravitreal triamcinolone (IVT) as initial pulse therapy followed by repeat
      intravitreal bevacizumab injections for maintenance treatment in neovascular age
      related macular degeneration (AMD). METHODS: In a prospective interventional case
      series, patients with subfoveal choroidal neovascularization (CNV) secondary to
      AMD underwent pulse therapy with single-session PDT according to the standard
      protocol followed by 1.25 mg IVB and 2 mg IVT 48 hours later. Best corrected
      visual acuity (BCVA) was assessed and optical coherence tomography (OCT) and
      fluorescein angiography (FA) were performed prior to treatment. BCVA and OCT
      measurements were repeated at 6 week intervals and FA was obtained after 12 weeks
      and when necessary thereafter. Repeat injections of IVB were performed based on
      fluorescein angiographic evidence of CNV leakage. RESULTS: This series included
      17 eyes of 17 patients with mean age of 67.6 +/- 7.2 years. Mean follow up
      duration was 50.4 +/- 15.5 weeks. Mean BCVA prior to treatment was 0.74 +/- 0.33
      logMAR which improved to 0.52 +/- 0.36 logMAR after 12 weeks (P = 0.012) and 0.41
      +/- 0.38 logMAR after 24 weeks (P = 0.001). Mean pretreatment central macular
      thickness (CMT) was 395 +/- 181 micro which was significantly reduced to 217 +/-
      69 micro (P = 0.005), 231 +/- 79 micro (P = 0.028) and 221 +/- 87 micro (P =
      0.05) six, twelve and twenty-four weeks after initial treatment respectively.
      Visual acuity improvement and CMT reduction was maintained during the follow-up
      period. IVB injections were repeated once, twice and three times in 10, 7 and 2
      eyes at a mean interval of 20.2 +/- 10.1, 19 +/- 13.7 and 15 +/- 1.4 weeks after
      initial therapy, respectively. CONCLUSION: Initial pulse triple therapy
      consisting of single-session PDT combined with IVB and IVT improves vision and
      reduces CMT in neovascular AMD. Repeat IVB injections maintain the visual gain
      from the initial combination therapy.

PMID- 17555601
TI  - Residual susceptibility to measles among young adults in Victoria, Australia
      following a national targeted measles-mumps-rubella vaccination campaign.
AB  - BACKGROUND: Past measles immunisation policies in Australia have resulted in a
      cohort of young adults who have been inadequately vaccinated, but who also have
      low levels of naturally acquired immunity because immunisation programs have
      decreased the circulation of wild virus. A measles-mumps-rubella (MMR)
      immunisation campaign aimed at addressing this susceptibility to measles among
      young adults was conducted in Australia in 2001-2. By estimating age-specific
      immunity, we aimed to evaluate the success of this campaign in the state of
      Victoria. METHODS: We conducted serosurveys after the young adult MMR program at
      state and national levels to estimate immunity among young adults born between
      1968-82. We compared results of the Victorian (state) surveys with the Victorian
      component of the national surveys and compared both surveys with surveys
      conducted before the campaign. We also reviewed all laboratory confirmed measles
      cases in Victoria between 2000-4. RESULTS: The Victorian state serosurveys
      indicated no significant change in immunity of the cohort following the young
      adult MMR campaign (83.9% immune pre and 85.5% immune post campaign) while the
      Victorian component of the national serosurvey indicated a significant decline in
      immunity (91.0% to 84.2%; p = 0.006). Both surveys indicated about 15%
      susceptibility to measles among young Victorian adults after the campaign.
      Measles outbreaks in Victoria between 2000-4 confirmed the susceptibility of
      young adults. Outbreaks involved a median of 2.5 cases with a median age of 24.5
      years. CONCLUSION: In Victoria, the young adult MMR program appears to have had
      no effect on residual susceptibility to measles among the 1968-82 birth cohort.
      Young adults in Victoria, as in other countries where past immunisation policies
      have left a residual susceptible cohort, represent a potential problem for the
      maintenance of measles elimination.

PMID- 17555602
TI  - Investigating the metabolic capabilities of Mycobacterium tuberculosis H37Rv
      using the in silico strain iNJ661 and proposing alternative drug targets.
AB  - BACKGROUND: Mycobacterium tuberculosis continues to be a major pathogen in the
      third world, killing almost 2 million people a year by the most recent estimates.
      Even in industrialized countries, the emergence of multi-drug resistant (MDR)
      strains of tuberculosis hails the need to develop additional medications for
      treatment. Many of the drugs used for treatment of tuberculosis target metabolic
      enzymes. Genome-scale models can be used for analysis, discovery, and as
      hypothesis generating tools, which will hopefully assist the rational drug
      development process. These models need to be able to assimilate data from large
      datasets and analyze them. RESULTS: We completed a bottom up reconstruction of
      the metabolic network of Mycobacterium tuberculosis H37Rv. This functional in
      silico bacterium, iNJ661, contains 661 genes and 939 reactions and can produce
      many of the complex compounds characteristic to tuberculosis, such as mycolic
      acids and mycocerosates. We grew this bacterium in silico on various media,
      analyzed the model in the context of multiple high-throughput data sets, and
      finally we analyzed the network in an 'unbiased' manner by calculating the Hard
      Coupled Reaction (HCR) sets, groups of reactions that are forced to operate in
      unison due to mass conservation and connectivity constraints. CONCLUSION:
      Although we observed growth rates comparable to experimental observations
      (doubling times ranging from about 12 to 24 hours) in different media,
      comparisons of gene essentiality with experimental data were less encouraging
      (generally about 55%). The reasons for the often conflicting results were multi
      fold, including gene expression variability under different conditions and lack
      of complete biological knowledge. Some of the inconsistencies between in vitro
      and in silico or in vivo and in silico results highlight specific loci that are
      worth further experimental investigations. Finally, by considering the HCR sets
      in the context of known drug targets for tuberculosis treatment we proposed new
      alternative, but equivalent drug targets.

PMID- 17555603
TI  - Stages of change for physical activity in adults from Southern Brazil: a
      population-based survey.
AB  - BACKGROUND: There is evidence that physical activity (PA) interventions tailored
      to individual's stages of change (SoC) are more effective in promote behavior
      change than "one-size-fits-all" interventions. However, only a few researches
      have investigated these stages towards PA behavior in representative samples of
      the population. Thus, the purpose of this study was to determine the prevalence
      and factors associated with the SoC for PA in a probabilistic sample of adults
      aged 20 years or over. METHODS: A population-based survey was undertaken in
      Pelotas, Southern Brazil, in 2005. An algorithm was applied to evaluate the SoC
      for PA, and PA was defined as being engaged in moderate-to-vigorous PA for at
      least 20 minutes on three times per week. The covariates collected in the
      questionnaire were: sex, age, skin color, marital status, education level,
      economic status, family income, smoking, body mass index (BMI) and self-reported
      health status. Data analyses were performed through Poisson and multinomial
      regression, taking the sampling design into account. RESULTS: Face-to-face
      interviews were applied to 3136 individuals, corresponding to a response rate of
      93.5%. The prevalence across the stages was as follows: 38.3% in
      precontemplation, 13.0% in contemplation, 19.5% in preparation, 5.2% in action
      and 24.0% in maintenance. The elderly, married, smokers, and those with lower
      socioeconomic status were less likely to adopt, initiate and maintain regular PA.
      CONCLUSION: Despite the all benefits of PA, a high proportion of adults from
      Southern Brazil are physically inactive and do not present intention to engage in
      regular PA. The profile of those who are inactive but intend to do PA resembles
      those who are physically active. The findings of the present study can contribute
      to improve health behaviors and to plan health promotion strategies aimed at
      increasing the level of PA in the community.

PMID- 17555604
TI  - Feasibility and costs of water fluoridation in remote Australian Aboriginal
      communities.
AB  - BACKGROUND: Fluoridation of public water supplies remains the key potential
      strategy for prevention of dental caries. The water supplies of many remote
      Indigenous communities do not contain adequate levels of natural fluoride. The
      small and dispersed nature of communities presents challenges for the provision
      of fluoridation infrastructure and until recently smaller settlements were
      considered unfavourable for cost-effective water fluoridation. Technological
      advances in water treatment and fluoridation are resulting in new and more cost
      effective water fluoridation options and recent cost analyses support water
      fluoridation for communities of less than 1,000 people. METHODS: Small scale
      fluoridation plants were installed in two remote Northern Territory communities
      in early 2004. Fluoride levels in community water supplies were expected to be
      monitored by local staff and by a remote electronic system. Site visits were
      undertaken by project investigators at commissioning and approximately two years
      later. Interviews were conducted with key informants and documentation pertaining
      to costs of the plants and operational reports were reviewed. RESULTS: The
      fluoridation plants were operational for about 80% of the trial period. A number
      of technical features that interfered with plant operation were identified and
      addressed though redesign. Management systems and the attitudes and capacity of
      operational staff also impacted on the effective functioning of the plants.
      Capital costs for the wider implementation of these plants in remote communities
      is estimated at about $US 94,000 with recurrent annual costs of $US 11,800 per
      unit. CONCLUSION: Operational issues during the trial indicate the need for
      effective management systems, including policy and funding responsibility.
      Reliable manufacturers and suppliers of equipment should be identified and
      contractual agreements should provide for ongoing technical assistance. Water
      fluoridation units should be considered as a potential priority component of
      health related infrastructure in at least the larger remote Indigenous
      communities which have inadequate levels of natural fluoride and high levels of
      dental caries.

PMID- 17555606
TI  - PediDraw: a web-based tool for drawing a pedigree in genetic counseling.
AB  - BACKGROUND: Drawing a pedigree is a prerequisite in genetic counseling. In
      medical records, a pedigree is useful to document the family history of the
      patient. Drawing a pedigree is also necessary in collecting genetic resources for
      medical research such as positional cloning. Currently, most pedigrees are drawn
      by hand or by drawing software. Due to the special requirements in a standardized
      pedigree, generating a pedigree by these methods is usually time-consuming and
      requires professionals. This limits the usage of a pedigree as demanded in remote
      diagnosis or online counseling from the counselees to send an electronic
      pedigree. RESULTS: We developed an online pedigree drawing tool, PediDraw, which
      enables users to generate pedigrees after inputting the family information step
      by-step on web. It outputs a pedigree or table to present a family history to the
      counselors. CONCLUSION: PediDraw is a user-friendly web-based drawing tool. It is
      accessible via Internet.

PMID- 17555607
TI  - Novel base catalysed rearrangement of sultone oximes to 1,2-benzisoxazole-3
      methane sulfonate derivatives.
AB  - A new process for the preparation of 1,2-benzisoxazole-3-methanesulfonates and 4
      oximino-2,3-dihydrobenzoxathiin-2,2-dioxides (sultone oximes) is described. These
      compounds are important intermediates for the preparation of zonisamide, an anti
      convulsant drug.

PMID- 17555605
TI  - Highly asymmetric rice genomes.
AB  - BACKGROUND: Individuals in the same species are assumed to share the same genomic
      set. However, it is not unusual to find an orthologous gene only in small subset
      of the species, and recent genomic studies suggest that structural rearrangements
      are very frequent between genomes in the same species. Two recently sequenced
      rice genomes Oryza sativa L. var. Nipponbare and O. sativa L. var. 93-11 provide
      an opportunity to systematically investigate the extent of the gene repertoire
      polymorphism, even though the genomic data of 93-11 derived from whole-short-gun
      sequencing is not yet as complete as that of Nipponbare. RESULTS: We compared
      gene contents and the genomic locations between two rice genomes. Our
      conservative estimates suggest that at least 10% of the genes in the genomes were
      either under presence/absence polymorphism (5.2%) or asymmetrically located
      between genomes (4.7%). The proportion of these "asymmetric genes" varied largely
      among gene groups, in which disease resistance (R) genes and the RLK kinase gene
      group had 11.6 and 7.8 times higher proportion of asymmetric genes than
      housekeeping genes (Myb and MADS). The significant difference in the proportion
      of asymmetric genes among gene groups suggests that natural selection is
      responsible for maintaining genomic asymmetry. On the other hand, the nucleotide
      diversity in 17 R genes under presence/absence polymorphism was generally low
      (average nucleotide diversity = 0.0051). CONCLUSION: The genomic symmetry was
      disrupted by 10% of asymmetric genes, which could cause genetic variation through
      more unequal crossing over, because these genes had no allelic counterparts to
      pair and then they were free to pair with homologues at non-allelic loci, during
      meiosis in heterozygotes. It might be a consequence of diversifying selection
      that increased the structural divergence among genomes, and of purifying
      selection that decreased nucleotide divergence in each R gene locus.

PMID- 17555608
TI  - An investigation of potential genetic determinants of propofol requirements and
      recovery from anaesthesia.
AB  - BACKGROUND AND OBJECTIVE: The objectives of this study were, firstly, to
      characterize the inter-patient variability in the dose of propofol required to
      achieve a bispectral index <70 and 'time to eye opening' following propofol
      infusion and, secondly, to determine if the pharmacodynamic parameter 'time to
      achieve bispectral index <70' was influenced by genotype of the sex-linked drug
      receptor gene GABRE or if pharmacokinetic parameters such as clearance and 'time
      to eye opening' were influenced by the genotype of the metabolizing enzyme
      CYP2B6. METHODS: One hundred and fifty patients received a standardized
      anaesthetic. Apparent systemic clearance values were estimated. Correlation was
      sought between carriers of different CYP2B6 and GABRE genotypes and apparent
      systemic clearance, 'time to achieve bispectral index <70' and 'time to eye
      opening'. RESULTS: Propofol induction/emergence characteristics varied, with slow
      recovery times in a subset of males. Time to loss of verbal contact and time to
      bispectral index <70 varied 6.6- and 4.3-fold, respectively. At emergence, there
      was a 15.5- to 111-fold variability in the measured time intervals. Clearance
      varied from 9.1 to 55.8 mL min-1 kg-1. The CYP2B6 C1459T (R487C) genotype
      frequencies were TT 1%, TC 22% and CC 67%. The three major haplotypes of CYP2B6
      (R487C, K262R and Q172H variants) were not significantly associated with time to
      eye opening or clearance. Clearance was similar in 487C carriers and 487RR
      genotypes. There was no statistically significant correlation between the four
      major haplotypes of GABRE variants investigated ([mRNA358]G/T, 20118C/T, 20326C/T
      and 20502 A/T) and the observed anaesthesia induction time. CONCLUSIONS: Great
      inter-patient variability exists in the dose of propofol required to achieve
      bispectral index <70, apparent systemic propofol clearance and time to eye
      opening. Common haplotypic differences at the CYP2B6 and GABRE genes do not
      appear to account for the majority of the observed inter-patient variability.

PMID- 17555609
TI  - Prediction of difficult tracheal intubation in Turkish patients: a multi-center
      methodological study.
AB  - BACKGROUND AND OBJECTIVE: Preoperative evaluation is important in the detection
      of patients at risk for difficult airway management. It is still unclear whether
      true prediction is possible and which variables should be chosen for evaluation.
      The aim of this prospective, multi-centre study was to investigate the incidence
      of difficult intubation, the sensitivity and positive predictive values of
      clinical screening tests and whether combining two or more of these tests will
      improve the prediction of difficult intubation in Turkish patients. METHODS:
      Seven study sites from six regions in Turkey participated in this study. One
      thousand six hundred and seventy-four ASA physical status I-III patients,
      scheduled to undergo elective surgery under general anaesthesia, were included.
      RESULTS: The incidence of difficult intubation was 4.8% and increased with age (P
      < 0.05). The incidence of difficult intubation was significantly higher in
      patients who had a Mallampati III or IV score, a decreased average thyromental
      and sternomental distance, decreased mouth opening, or decreased protrusion of
      the mandible (P < 0.05). Mouth opening and Mallampati III-IV were found to be the
      most sensitive criteria when used alone (43% and 35%, respectively). Combination
      of tests did not improve these results. CONCLUSIONS: There is still no individual
      test or a combination of tests that predict difficult intubations accurately.
      Tests with higher specificity despite low positive predictive value are needed.

PMID- 17555610
TI  - Preconditioning and protection against ischaemia-reperfusion in non-cardiac
      organs: a place for volatile anaesthetics?
AB  - There is an increasing body of evidence that volatile anaesthetics protect
      myocardium against ischaemic insult by a mechanism termed 'anaesthetic
      preconditioning'. Anaesthetic preconditioning and ischaemic preconditioning share
      several common mechanisms of action. Since ischaemic preconditioning has been
      demonstrated in organs other than the heart, anaesthetic preconditioning might
      also apply in these organs and have significant clinical applications in surgical
      procedures carrying a high risk of ischaemia-reperfusion injury. After a brief
      review on myocardial preconditioning, experimental and clinical data on
      preconditioning in non-cardiac tissues will be presented. Potential benefits of
      anaesthetic preconditioning during non-cardiac surgery will be addressed.

PMID- 17555613
TI  - Infrared-ultraviolet sum-frequency generation spectrometer with a wide tunability
      of the ultraviolet probe.
AB  - We have constructed a multiplex infrared-ultraviolet (IR-UV) sum-frequency
      generation (SFG) spectrometer that has a wide tunable range (235-390 nm) of the
      UV probe wavelength. The tunable UV probe was obtained by doubling the signal
      output of an optical parametric amplifier pumped by a 400 nm picosecond pulse. A
      prism monochromator was used as a tunable sharp-cut bandpass filter to reduce
      stray light due to the scattering of the UV probe so that any wavelength within
      the tunable range can be chosen as that of the UV probe. The SFG spectra of p
      mercaptobenzoic acid on a gold substrate was measured with 289 and 334 nm UV
      probes. The SFG vibrational band intensities due to the carbonyl stretch mode and
      a phenyl ring stretch mode measured with the 289 nm probe were approximately
      three times larger than those measured with the 334 nm probe. The enhancement was
      ascribed to an electronic resonant effect.

PMID- 17555611
TI  - Economic burden of   cardiovascular events and   fractures among patients with  
      end-stage renal disease.
AB  - OBJECTIVE: To quantify direct medical costs of fractures and cardiovascular
      diseases among end-stage renal disease (ESRD) patients. METHODS: Medicare claims
      data from year 2001 of the United States Renal Data System were used to quantify
      direct medical costs of acute episodic events (acute myocardial infarction (MI),
      stroke, heart valve repair, heart valve replacement, fractures) and chronic
      conditions (arrhythmia, peripheral vascular disease (PVD), heart valve disease
      (HVD), congestive heart failure (CHF), coronary heart disease, and non-acute
      stroke). Costs of hospitalized episodes of arrhythmia, PVD, CHF, and angina were
      also quantified. For acute events, costs were quantified using an episode-of-care
      approach. For chronic conditions, annualized costs were reported. Only costs
      specific to the events or conditions of interest were included and reported, in
      2006 US dollars. Drug and dialysis-related costs were excluded. Diagnosis and
      procedure codes were used to identify these events and conditions. RESULTS: Among
      acute events analyzed as clinical episodes, PVD ($358 million) was associated
      with the greatest economic burden, followed by CHF, arrhythmia, angina, acute MI,
      heart valve replacement, hip fracture, acute stroke, heart valve repair,
      vertebral fracture, and pelvic fracture ($8.6 million). The cost per episode
      ranged from approximately $12,000 to 104,000. Among chronic conditions, CHF ($681
      million) contributed the greatest economic burden; HVD ($100 million) contributed
      the least. The costs per patient-year ranged from $23,000 to 45,000 among chronic
      conditions. The costing methodology utilized could contribute to an underestimate
      of the economic impact of each condition; therefore these results are considered
      conservative. CONCLUSION: The economic burden of these selected conditions was
      substantial to health services payers who finance ESRD patient care. Episodic
      costs were high for most acute events.

PMID- 17555614
TI  - Temperature-controlled confocal Raman microscopy to detect phase transitions in
      phospholipid vesicles.
AB  - Optical-trapping confocal Raman microscopy enhances the capabilities of
      traditional Raman spectroscopy for the analysis of small particles by
      significantly reducing the sampling volume and minimizing background signal from
      the particle surroundings. Chemical composition and structural information can be
      obtained from optically trapped particles in aqueous solution without the need
      for labeling or extensive sample preparation. In this work, the challenges of
      measuring temperature dependent changes in suspended particles are addressed with
      the development of a small-volume, thermally conductive sample cell attached to a
      temperature-controlled microscope stage. To demonstrate its function, the gel to
      liquid-crystalline phase transitions of optically trapped lipid vesicles,
      composed of pure 1,2-ditridecanoyl-sn-glycero-3-phosphocholine (DTPC), 1,2
      dimyristoyl-sn-glycero-3-phosphocholine (DMPC), and 1,2-dipalmitoyl-sn-glycero-3
      phosphocholine (DPPC), were detected by changes in Raman spectra of the lipid
      bilayer. The Raman scattering data were found to correlate well with differential
      scanning calorimetry (DSC) results.

PMID- 17555615
TI  - Applicability of fiber-optic-based Raman probes for on-line reaction monitoring
      of high-pressure catalytic hydrogenation reactions.
AB  - This study evaluates the applicability of fiber-optic-based Raman probes for on
      line reaction monitoring of high-pressure catalytic hydrogenation reactions in
      batch autoclaves. First, based on trends in the strong intensity of the 945 cm(
      1) C-O-C vibration of 1,3-dioxolane, the effect of various experimental
      parameters on sensitivity was evaluated and can be summarized as follows: (1)
      above 500 rpm a linear increase in stirring speed induces a linear decrease in
      Raman intensity; (2) a linear increase in hydrogen pressure also leads to a
      linear decrease of the Raman signal; (3) linear temperature elevation
      exponentially decreases the Raman intensity; and (4) increasing the catalyst
      particle concentration results in a steep nonlinear decrease of the Raman signal.
      Light scattering by gas bubbles, or combined scattering and absorption by (black)
      catalyst particles, reducing the amount of light collected by the optical fiber
      probe, explain the observed experimental trends. Second, the sensitivity of Raman
      spectroscopy was directly compared with attenuated total reflection-Fourier
      transform infrared (ATR-FT-IR) spectroscopy in the analysis of three different
      hydrogenation reactions over a Cu-ZnO catalyst. From the applied target
      molecules, diethyl maleate hydrogenation could be very well analyzed by Raman
      spectroscopy due to the high Raman scattering efficiency of the C=C bond, while
      for analysis of the hydrogenation of gamma-butyrolactone or 1-butanal, ATR-FT-IR
      is the technique of choice.

PMID- 17555616
TI  - Reproducible surface-enhanced Raman scattering spectra of bacteria on aggregated
      silver nanoparticles.
AB  - Surface-enhanced Raman scattering (SERS) is proven to be a powerful technique for
      rapid identification and discrimination of microorganisms. However, due to the
      heterogeneous nature of the samples, the acquisition of reproducible spectra
      hinders the further development of the technique. In this study, we demonstrate
      the influence of the experimental conditions on SERS spectra. Then, we report a
      simple sample preparation method coupled with a light microscope attached to a
      Raman spectrometer to find a proper spot on the sample to acquire reproducible
      SERS spectra. This method utilizes the excited surface plasmons of the aggregated
      silver nanoparticles to visualize the spots on the sample. The samples are
      prepared using the concentrated silver colloidal solutions. The collection time
      for one spectrum is 10 s and each spectrum is a very good representative of the
      other spectra acquired from the same sample. The nature of the surface charge of
      the silver nanoparticles influences the spectral features by determining the
      strength of the interactions between nanoparticles and bacteria and the
      aggregation properties of the nanoparticles. Although increasing the colloid
      concentration in the sample resulted in reproducible spectra from arbitrary
      points on the sample, a great variation from sample to sample prepared with the
      different colloidal solution concentrations is observed.

PMID- 17555617
TI  - Background-free coherent anti-stokes Raman scattering of gas- and liquid-phase
      samples in a mesoporous silica aerogel host.
AB  - Efficient time-resolved coherent anti-Stokes Raman scattering (CARS) of
      atmospheric nitrogen and ethanol trapped in a nanoporous silica aerogel matrix is
      demonstrated. Silica aerogel hosts are attractive for analytical CARS
      spectroscopy due to their high porosity/low density, low refractive index, and
      low scattering cross-section. Differences between the resonant and nonresonant
      parts of the nonlinear optical susceptibilities lead to much longer relaxation
      times for analytes compared to the matrix. Time-resolved CARS can then be used to
      obtain a nearly background-free measurement at characteristic vibrations of the
      analyte. These results demonstrate the potential of this approach for rapid,
      sensitive, background-free analyses of analytes entrapped in the aerogel pores,
      which may be advantageous for some environmental, chemical, and biological
      sensing applications.

PMID- 17555618
TI  - Near-infrared spectroscopic method for real-time monitoring of pharmaceutical
      powders during voiding.
AB  - A near-infrared (NIR) spectroscopic method has been developed to monitor flowing
      pharmaceutical powders during their voiding and detect post-blending segregation.
      The method is capable of providing both chemical and physical information
      (particle size differences) on the flowing pharmaceutical powders. Particle size
      differences are widely recognized as the predominant driver for segregation.
      Pharmaceutical powders may segregate following blending as they are voided down
      pipes to compressing machines, increasing the variability of the drug content and
      dissolution of the final product tablets because of segregation. NIR diffuse
      reflectance spectra of pharmaceutical powders were obtained following voiding
      through a six-foot pipe. Spectral subtraction was used to eliminate baseline
      differences but maintain particle size differences. The NIR spectra indicated
      differences in the particle size of the flowing powder. Particle size differences
      were also tracked throughout the voiding of pharmaceutical powders by plotting
      the absorbance at 1536 nm. The method was also applied to the voiding of two
      layers of lactose particles with different particle sizes. The system described
      in this report provides an approach to study post-blending segregation in
      pharmaceutical powders and other relevant materials.

PMID- 17555619
TI  - Blank augmentation protocol for improving the robustness of multivariate
      calibrations.
AB  - An updating procedure is described for improving the robustness of multivariate
      calibration models based on near-infrared spectroscopy. Employing a single blank
      sample containing no analyte, repeated spectra are acquired during the
      instrumental warm-up period. These spectra are used to capture the instrumental
      profile on the analysis day in a way that can be used to update a previously
      computed calibration model. By augmenting the original spectra of the calibration
      samples with a group of spectra collected from the blank sample, an updated model
      can be computed that incorporates any instrumental drift that has occurred. This
      protocol is evaluated in the context of an analysis of physiological levels of
      glucose in a simulated biological matrix designed to mimic blood plasma.
      Employing data of calibration and prediction samples acquired over approximately
      six months, procedures are studied for implementing the algorithm in conjunction
      with calibration models based on partial least squares (PLS) regression. Over the
      range of 1-20 mM glucose, the final algorithm achieves a standard error of
      prediction (SEP) of 0.79 mM when the augmented PLS model is applied to data
      collected 176 days after the collection of the calibration spectra. Without
      updating, the original PLS model produces a seriously degraded SEP of 13.4 mM.

PMID- 17555620
TI  - On-line recalibration of spectral measurements using metabolite injections and
      dynamic orthogonal projection.
AB  - Spectrometers are enjoying increasing popularity in bioprocess monitoring due to
      their non-invasiveness and in situ sterilizability. Their on-line applicability
      and high measurement frequency create an interesting opportunity for process
      control and optimization tasks. However, building and maintaining a robust
      calibration model for the on-line estimation of key variables of interest (e.g.,
      concentrations of selected metabolites) is time consuming and costly. One of the
      main drawbacks of using infrared (IR) spectrometers on-line is that IR spectra
      are compromised by both long-term drifts and short-term sudden shifts due to
      instrumental effects or process shifts that might be unseen during calibration.
      The effect of instrumental drifts can normally be reduced by referencing the
      measurements against a background solution, but this option is difficult to
      implement for single-beam instruments due to sterility issues. In this work, in
      order to maintain the robustness of calibration models for single-beam IR and to
      increase resistance to process and instrumental drifts, planned spikes of small
      amounts of analytes were injected periodically into the monitored medium. The
      corresponding measured difference spectra were scaled-up and used as reference
      measurements for updating the calibration model in real time based on dynamic
      orthogonal projection (DOP). Applying this technique led to a noticeable decrease
      in the standard error of prediction of metabolite concentrations monitored during
      an anaerobic fermentation of the yeast Saccharomyces cerevisiae.

PMID- 17555621
TI  - Chemical imaging of latent fingerprint residues.
AB  - In situ attenuated total reflection Fourier transform infrared (ATR-FT-IR)
      spectroscopic imaging has been used to obtain chemical images of fingerprints
      under controlled humidity and temperature. The distribution of lipid and amino
      acid components in the fingerprints from different donors left on the surface of
      the ZnSe crystal has been studied using an in situ FT-IR spectroscopic imaging
      approach under a controlled environment and studied as a function of time.
      Univariate and multivariate analyses were employed to analyze the spectroscopic
      dataset. Changes in the spectra of lipids with temperature and time have been
      detected. This information is needed to understand aging of the fingerprints. The
      ATR-FT-IR spectroscopic imaging offers a new and complementary means for studying
      the chemistry of fingerprints that are left pristine for further analysis. This
      study demonstrates the potential for visualizing the chemical changes of
      fingerprints for forensic applications by spectroscopic imaging.

PMID- 17555622
TI  - Use of polarized spectroscopy as a tool for examining the microstructure of
      cellulosic textile fibers.
AB  - Textile artifacts form a vital part of our cultural heritage. In order to
      determine appropriate methods of conservation, storage, and display, it is
      important to understand the current physical state of an artifact, as effected by
      the microstructure of the component fibers. The semi-crystalline nature of the
      constituent polymer aggregates, the degree of crystallinity, and the crystallite
      orientation have a significant influence on mechanical properties. The value of
      polarized Fourier transform infrared (FT-IR) spectroscopy in probing these
      aspects of cellulosic fibers has been assessed. A variety of representative
      fibers (both natural plant fibers and regenerated materials) were examined by
      polarized attenuated total reflection spectroscopy (Pol-ATR) and polarized
      infrared microspectroscopy (Pol-microIR); the former is a surface sampling
      technique and the latter is a transmission technique. The introduction of a
      polarizer into the system allows the alignment as well as the nature of bonds to
      be determined, and thus the presence and extent of crystallinity or long range
      ordering can be investigated. Using the data from the Pol-ATR experiments, it was
      found to be possible to derive the principle alignment of the cellulose polymer
      with respect to the fiber axis, along with an indication of the total cellulose
      crystallinity of the material, as measured by a crystallinity parameter, Chi. The
      Pol-microIR spectra, on the other hand, yielded more limited information,
      particularly when considering plant fibers with more complex microstructures.

PMID- 17555623
TI  - Grazing angle attenuated total reflection spectroscopy: fields at the interface
      and source of the enhancement.
AB  - With the tremendous growth in the semiconductor and coatings industries,
      spectroscopic methods of examining extremely thin films on high refractive index
      substrates have become increasingly important. One infrared method for analyzing
      monolayers on substrates such as silicon and gold that has recently gained
      popularity is 'grazing' or high angle of incidence attenuated total reflection
      (ATR) spectroscopy. This paper investigates the directional electric field
      strengths and the extraordinary sensitivity achieved by using the grazing angle
      ATR method for analyzing monolayers on silicon substrates.

PMID- 17555624
TI  - On the behavior of indole-containing species sequestered within reverse micelles
      at sub-zero temperatures.
AB  - We report on the effects of temperature (+30 to -100 degrees C) on the
      fluorescence from N-acetyl tryptophanamide (NATA) and human serum albumin (HSA)
      sequestered within Aerosol-OT (AOT) reversed micelles. NATA reports
      simultaneously from the polar and non-polar side of the reverse micelle
      interface. As the sample temperature decreases, the relative fraction of NATA
      molecules associated with the polar side increases. This redistribution process
      is characterized by DeltaH = -14.8 +/- 0.6 kJ/mol and DeltaS = -54 +/- 2 J/(K
      mol). The activation energy for thermal quenching (E(a,TQ)) associated with the
      polar side NATA molecules is 6.7 kJ/mol before the micelles have shed water and
      1.0 kJ/mol after water shedding (below approximately -20 degrees C). The time
      resolved fluorescence intensity decay for tryptophan-214 in HSA is triple
      exponential. We suggest that these lifetimes arise from three indole residue
      conformations in equilibrium. Cooling the sample causes a freezing-in of the
      least quenched conformer; the other conformers are frozen out. The E(a,TQ) value
      for the shortest lifetime component is 6 kJ/mol. The E(a,TQ) for the long and
      intermediate lifetime components are equivalent (approximately 1.5 kJ/mol).

PMID- 17555625
TI  - A probability-based spectroscopic diagnostic algorithm for simultaneous
      discrimination of brain tumor and tumor margins from normal brain tissue.
AB  - This paper reports the development of a probability-based spectroscopic
      diagnostic algorithm capable of simultaneously discriminating tumor core and
      tumor margins from normal human brain tissues. The algorithm uses a nonlinear
      method for feature extraction based on maximum representation and discrimination
      feature (MRDF) and a Bayesian method for classification based on sparse
      multinomial logistic regression (SMLR). Both the autofluorescence and the diffuse
      reflectance spectra acquired in vivo from patients undergoing craniotomy or
      temporal lobectomy at the Vanderbilt University Medical Center were used to train
      and validate the algorithm. The classification accuracy was observed to be
      approximately 96%, 80%, and 97% for the tumor, tumor margin, and normal brain
      tissues, respectively, for the training data set and approximately 96%, 94%, and
      100%, respectively, for the corresponding tissue types in an independent
      validation data set. The inherently multi-class nature of the algorithm
      facilitates a rapid and simultaneous classification of tissue spectra into
      various tissue categories without the need for a hierarchical multi-step binary
      classification scheme. Further, the probabilistic nature of the algorithm makes
      it possible to quantitatively assess the certainty of the classification and
      recheck the samples that are classified with higher relative uncertainty.

PMID- 17555626
TI  - In situ analytical assessment and chemical imaging of historical buildings using
      a man-portable laser system.
AB  - In this work, the capability of laser-induced breakdown spectrometry for the in
      situ analytical assessment and chemical mapping of the facade of the cathedral of
      Malaga (Spain) has been demonstrated. The task required the use of a portable
      laser analyzer that allowed real-time spectral acquisitions in the field. A man
      portable laser, based on a Q-switched Nd:YAG laser operating at its fundamental
      wavelength, has been utilized to generate a LIBS plasma of the sample surface. A
      chemical characterization of the different materials employed in the construction
      of this building has been performed. The purpose of this study was to use LIBS
      spectrochemical analysis to qualitatively discriminate between sandstone,
      limestone, marble, and cement mortar, which are the main components used in this
      class of historical monument. The field analysis was performed in two zones: the
      northern facade and the "girola"; the total areas of analysis of the two regions
      were 250 m(2) and 650 m(2), respectively. Chemical images of Si/Ca and Ca/Mg
      ratios from both parts of the building were generated. During the measurement
      campaign, a protocol of analysis was chosen so as to achieve an accurate
      description of the building materials with respectable spatial resolutions.

PMID- 17555627
TI  - Laser diagnostics of welding plasma by polarization spectroscopy.
AB  - The application of polarization spectroscopy (PS) to detect atomic species in an
      atmospheric pressure welding plasma has been demonstrated. PS spectra of Na
      atoms, seeded in the shielding gas flow of a gas tungsten arc welding (GTAW)
      plasma, are presented at different pump beam energies. The nature of the PS
      technique was found to be very efficient in suppressing the high background
      emission associated with the welding plasma. The PS spectral profiles appear to
      be Lorentzian and Lorentzian cubed for high and low pump beam energy,
      respectively. The effect of beam steering, due to the thermal gradient in the
      interaction plasma zone, was addressed. It was found that there is 2% unavoidable
      error in the detectable PS signal.

PMID- 17555628
TI  - GC-MS studies on the regioisomeric 2,3- and 3,4-methylenedioxyphenethylamines
      related to MDEA, MDMMA, and MBDB.
AB  - Three regioisomeric 3,4-methylenedioxyphenethylamines having the same molecular
      weight and major mass spectral fragments of equal mass have been reported as
      drugs of abuse in forensic studies in recent years. These compounds are 3,4
      methylenedioxy-N-ethylamphetamine (MDEA), 3,4-methylenedioxy-N-N
      dimethylamphetamine (MDMMA), and N-methyl-1-(3,4-methylenedioxyphenyl)-2
      butanamine (MBDB). The mass spectra of the regioisomers (2,3
      methylenedioxyphenethylamines) are essentially equal to the three compounds
      reported as drugs of abuse. This paper reports the synthesis, mass spectral
      characterization, and chromatographic analysis of these six regioisomeric amines.
      The six regioisomeric methylenedioxyphenethylamines are synthesized from
      commercially available starting materials. The electron impact mass spectra of
      these regioisomers show some variation in the relative intensity of the major
      ions with only a couple of minor ions that may indicate side chain specific
      fragments. Differentiation by mass spectrometry is only possible after the
      formation of the perfluoroacyl derivatives, pentafluoropropionylamides (PFPA) and
      heptafluorobutrylamides (HFBA). Gas chromatographic separation on non-polar
      stationary phases (Rtx-1 and Rtx-5) is not successful at resolving the three 3,4
      methylenedioxyphenethylamines from the three 2,3-methylenedioxyphenethylamines as
      the underivatized amines. The six underivatized amines are resolved on the more
      polar trifluoropropylmethyl polysiloxane Rtx-200 stationary phase as well as a
      permethylated beta-cyclodextran Rtx-bDEX stationary phase. Gas chromatographic
      separation is successful at resolving the four PFPA and the four HFBA derivatives
      on the Rtx-200 stationary phase as well as the permethylated beta-cyclodextran
      stationary phase. The 2,3-methylenedioxyphenethylamine derivatives (compounds 4
      and 6) eluted before the 3,4-methylenedioxyphenethylamine derivatives (compounds
      1 and 3) as both the PFPA and HFBA derivatives.

PMID- 17555629
TI  - Rapid determination of bisphosphonates by ion chromatography with indirect UV
      detection.
AB  - Rapid methods for etidronate, clodronate, pamidronate, and alendronate assays are
      presented. The methods are based on ion chromatography with indirect UV
      detection, which avoids the need for chemical derivatization procedures. Each
      compound is analyzed on an individual basis. There is no need for having
      separation among these analytes because the aim of the proposed methods is to
      analyze each compound separately either in bulk material or pharmaceuticals.
      Phenosphere (150 x 2.0-mm, 5 microm) and Sphereclone (250 x 2.0-mm, 5 microm)
      anion exchange columns were employed with sodium citrate (20mM) as the mobile
      phase. The methods are simple, rapid (analysis time of 5 min for etidronate and
      clodronate and 7 min for alendronate and pamidronate), and demonstrate precision
      (relative standard deviation was lower than 2.0% in all concentrations),
      accuracy, and specificity. Calibration curves are linear with r(2) > 0.99 over
      the concentration range of 50 to 400 microg/mL for etidronate and clodronate, and
      of 100 to 500 microg/mL for pamidronate and alendronate. Furthermore, they
      employed silica-based columns, which are cheaper than polymeric columns
      frequently used in previous reported methods.

PMID- 17555630
TI  - Development of a method for the determination of ibafloxacin in plasma by HPLC
      with flourescence detection and its application to a pharmacokinetic study.
AB  - A simple, rapid, and sensitive high-performance liquid chromatographic method is
      developed for the determination of ibafloxacin in rabbit plasma. Plasma proteins
      are precipitated with acetonitrile, and after extraction with methylene chloride
      followed by desecation, ibafloxacin is determined by reversed-phase
      chromatography with fluorescence detection exciting at 330 nm and emission at 368
      nm. Peaks corresponding to ibafloxacin and the internal standard (salycilic acid)
      are obtained at 9.8 and 5.2 min, respectively. The method is validated for a
      limit of quantitation of 10 ng/mL. The intraday relative standard deviation
      ranges from 4.78-7.15%, and the interday precision ranges from 1.32-4.03%. The
      method shows linearity for the two calibration curves used (10-100 ng/mL and 100
      2000 ng/mL). The procedure described is applied successfully to a
      pharmacokinetics study of ibafloxacin in rabbits.

PMID- 17555631
TI  - Chiral separation of ephedrine isomers by capillary electrophoresis using bovine
      serum albumin as a buffer additive.
AB  - A method utilizing bovine serum albumin (BSA) as buffer additive for chiral
      separation by means of capillary electrophoresis is described. Parameters that
      affect chiral separation, such as buffer pH, buffer concentration, BSA
      concentration, and organic modifier, are investigated. Baseline resolution of
      ephedrine-pseudoephedrine and norephedrine-norpseudoephedrine isomers are
      achieved in an uncoated capillary with a 20 mmol/L phosphate buffer at pH 9.0 in
      the presence of 10 micromol/L BSA and 15% (v/v) 2-propanol at 25 degrees C. The
      developed method can be applied for the analysis of ephedra plant extracts that
      contain the four test drugs.

PMID- 17555632
TI  - Simultaneous determination of caffeine, ergotamine, and metamizol in solid
      pharmaceutical formulation by HPTLC-UV-FLD with mass confirmation by online HPTLC
      ESI-MS.
AB  - A new high-throughput method is developed to quantify caffeine, ergotamine, and
      metamizol in a solid pharmaceutical formulation. After dissolution, the compounds
      are separated on silica gel 60 F(254) high-performance thin-layer chromatography
      (HPTLC) plates with ethyl acetate-methanol-ammonia 90:15:1 (v/v/v) as the mobile
      phase. Detection is performed by UV absorption at 274 nm for caffeine and
      metamizol, and by fluorescence at 313 /> 340 nm for ergotamine. Calibrations are
      linear or polynomial with determination coefficients (R(2)) >or= 0.9986.
      Recoveries of the three compounds are between 95% and 102% at three different
      concentration levels. Repeatability [relative standard deviation (RSD)] of all
      substances in the matrix is between +/- 0.9% and +/- 1.7%. Intermediate precision
      (RSD) of the three compounds range from +/- 2.0% to +/- 3.1%. Mass confirmation
      is performed by a single quadrupole mass spectrometry in positive electrospray
      ionization full scan mode for caffeine and ergotamine and in negative mode for
      metamizol. The results proved that this method is a simple and reliable
      alternative for routine analysis.

PMID- 17555633
TI  - Effects of ionic liquid as additive and the pH of the mobile phase on the
      retention factors of amino benzoic acids in RP-HPLC.
AB  - As an organic salt, ionic liquids are widely used as new solvent media. In this
      paper, three positional isomers, such as o-amino benzoic acid, m-amino benzoic
      acid, and p-amino benzoic acid are separated with four different ionic liquids as
      additives to the mobile phase using reversed-phase (RP) high-performance liquid
      chromatography (HPLC). Amino benzoic acids are biologically active substances;
      the p-isomer is present in a group of water-soluble vitamins and is widely known
      as a sunscreen agent. The ionic liquids used are 1-butyl-3-methylimidazolium
      tetrafluoroborate, 1-ethyl-3-methylimidazolium tetrafluoroborate, 1-ethyl-3
      methylimidazolium methylsulfate, and 1-octyl-3-methylimidazolium methylsulfate.
      The effects of the length of the alkyl group on the imidazolium ring and its
      counterion, the concentrations of the ionic liquid, and the effect of the pH of
      the mobile phase on the retention factor of the amino benzoic acid isomers are
      studied. Separation with the ionic liquid in the eluent was better than the
      separation without the ionic liquid. The pH mainly affected the retention and
      elution order of the solutes in RP-HPLC.

PMID- 17555634
TI  - Thin-layer chromatography of aluminium: quantitative densitometric determination
      of Fe2+, Ni2+, Cu2+, and Si4+.
AB  - Thin-layer chromatography in combination with scanning densitometry is used as a
      tool for the quantitative determination of some impurity and additive elements in
      aluminium. Microgram levels of iron, silicon, copper, nickel, titanium,
      magnesium, manganese, and zinc present in a high concentration aluminium matrix
      is detected, and selective separations of some of these elements are achieved on
      silica gel H layers developed with a mobile phase containing aqueous sodium
      chloride solution. The quantitative determination of iron, silicon, nickel, and
      copper are obtained from the densitometric evaluation of chromatograms and are
      compared with the respective optical emission spectral analytical data.

PMID- 17555635
TI  - Determination of ethambutol hydrochloride in the combination tablets by precolumn
      derivatization.
AB  - A new high-performance liquid chromatography method for the quantitative
      determination of ethambutol hydrochloride in combination tablets is presented.
      Ethambutol is derivatized with phenylethylisocyanatate at room temperature (22 +/
      2 degrees C) for 5 min. Separation is performed by a C(18) column using methanol
      water-glacial acetic acid (70:30:0.2, v/v/v) as the mobile phase. The method is
      linear for drug concentrations in the range of 20-120 microg/mL (r=0.9995). The
      intra- and inter-day precisions are lower than 1.46% and 2.22%, respectively. The
      average recovery of the samples at three levels is 99.8%. The results show that
      derivatization of ethambutol is stable at 30 degrees C for 24 h. This method is
      simple, rapid, and stable in the presence of common excipients and
      antituberculosis drugs in the tablets.

PMID- 17555636
TI  - Determination of theobromine, theophylline, and caffeine in by-products of
      cupuacu and cacao seeds by high-performance liquid chromatography.
AB  - Theobromine, theophylline, and caffeine are determined simultaneously by a rapid
      and selective reversed-phase high-performance liquid chromatography (HPLC) method
      with UV detection in by-products of cupuacu and cacao seeds. The determination is
      carried out in the raw and roasted ground cupuacu seeds and in the corresponding
      powders obtained after pressure treatment. The by-products of both cupuacu seeds
      and cacao seeds are obtained under the same technological conditions. The HPLC
      method uses isocratic elution with a mobile phase of methanol-water-acetic acid
      (80:19:1) (v/v) at a flow rate of 1 mL/min and UV absorbance detection at 275 nm.
      Total elution time for these analytes is less than 10 min, and the detection
      limit for all analytes is 0.1 mg/g. The amounts of theobromine and caffeine found
      in all the cupuacu samples are one or more orders of magnitude lower than those
      from cacao. Theophylline is found in all cacao samples except for the roasted
      ground paste, and it is only found in the roasted ground paste in the cupuacu
      samples.

PMID- 17555637
TI  - Separation and characterization of particles in natural water and soil using flow
      field-flow fractionation.
AB  - Flow field-flow fractionation (FlFFF) is used to characterize particles in
      natural water (ground and surface water) and soil. The opposed flow sample
      concentration (OFSC) mode of FlFFF (OFSC-FlFFF) is employed, where the colloidal
      sample is continuously fed into the channel so that the particles are focused
      into a narrow band near the inlet of the FlFFF channel before the separation is
      initiated. There is no need for stopping the flow for the sample relaxation,
      which is usually required in conventional FlFFF operations. First, the OFSC-FlFFF
      is tested with mixtures of polystyrene latex spheres. Then the OFSC-FlFFF
      procedure is optimized for the analysis of particles in natural water and soil by
      varying various experimental parameters including the flow rates. Ground water of
      up to 100 mL has been successfully loaded, concentrated, and characterized by
      OFSC-FlFFF. Results show that the OFSC-FlFFF provides a simplified alternative to
      existing off-line concentration procedures, and it shows high potential for
      application to analysis of dilute colloidal particles in environmental water. The
      composition of the samples was analyzed using atomic absorption spectrometry.

PMID- 17555638
TI  - Analysis of western redcedar (Thuja plicata Donn) heartwood components by HPLC as
      a possible screening tool for trees with enhanced natural durability.
AB  - A method is described for the quantitative analysis of seven known compounds,
      specifically plicatic acid, thujaplicatin methyl ether, beta-thujaplicin, gamma
      thujaplicin, beta-thujaplicinol, thujic acid, and methyl thujate, in the ethanol
      extract of second growth western redcedar heartwood (Thuja plicata Donn) by high
      performance liquid chromatography using diode array detection. The para bromo
      phenacyl ester of crotonic acid is synthesized for use as the internal standard
      for the method. Separation of compounds covering a wide range of polarities is
      achieved using an Inertsil ODS 3 3-micro column. Twenty seven second growth trees
      ranging in age from 40 to 125 years, originating from the coastal and interior
      regions of British Columbia, are selected for analysis and profiled using the
      described method. Samples consisting of five growth rings each are analyzed from
      the heartwood-sapwood boundary to the pith for each tree. Substantial variation
      in most heartwood compounds are detected within and between trees within a
      region. Significant variation in beta-thujaplicin, the ratio between gamma- and
      beta-thujaplicin, and methyl thujate is detected between coastal and interior
      populations.

PMID- 17555639
TI  - Fluconazol method validation by RP-HPLC for determination in biological skin
      matrices.
AB  - The bis-triazole antifungal fluconazole (FCZ) is used in the systemic treatment
      of superficial mycoses. The inconvenience of drug interactions and incidence of
      adverse reactions occurs in approximately 16% of patients, despite several
      advantages against systemic fungal infections. Because its pharmacokinetics
      profile is favorable to cutaneous accumulation, it presents a prominent
      importance in the treatment of superficial mycoses. This study shows FCZ method
      validation by reversed-phase high-performance liquid chromatography in the linear
      range of 2 to 32 microg/mL, which suitable for application in biological matrices
      after topical permeation studies. The method is tested in simulated FCZ alcoholic
      solution applied to skin extracts after in vitro permeation studies using Franz
      cells. Recovery shows good results (in the range 75.0% +/- 4.1% to 82.0% +/-
      6.6%) regarding the biological matrices.

PMID- 17555640
TI  - Quantification of atrazine, phenylurea, and sulfonylurea herbicide metabolites in
      urine by high-performance liquid chromatography-tandem mass spectrometry.
AB  - We developed a high-performance liquid chromatography-tandem mass spectrometry
      (HPLC-MS-MS) method to measure metabolites of atrazine, phenylurea, and
      sulfonylurea herbicides in human urine. The metabolites measured in the method
      include atrazine mercapturate, desethyl atrazine, and desisopropyl atrazine as
      markers of atrazine exposure; dichlorophenyl urea, dichlorophenylmethyl urea,
      diuron, and linuron as markers of phenylurea herbicide exposure; and
      dimethoxypyrimidine, dimethylpyrimidine, and methoxymethyl triazine as markers
      for sulfonylurea herbicide exposure. The metabolites were extracted from urine by
      simple solid-phase extraction using a mixed-bed cartridge and were analyzed by
      HPLC-MS-MS. Quantification of the atrazine metabolites was achieved using isotope
      dilution calibration. The remaining metabolites were quantified using similarly
      structured chemicals as internal standards. Extraction recoveries ranged from 88%
      to 104% (n = 5). Limits of detection for the entire method ranged from 0.125 to 1
      ng/mL, and the average relative standard deviation of repeat measurements was
      about 13% (n = 30).

PMID- 17555641
TI  - Detection of conjugated 11-nor-Delta9-tetrahydrocannabinol-9-carboxylic acid in
      oral fluid.
AB  - The presence of the conjugated marijuana metabolite 11-nor-Delta(9)
      tetrahydrocannabinol-9-carboxylic acid (THCA) glucuronide in oral fluid specimens
      is described for the first time. Oral fluid specimens were collected using a
      Quantisal device and analyzed for the presence of THCA using two-dimensional gas
      chromatography with mass spectrometric (GC-MS) detection both before and after
      hydrolysis. The nature of the conjugation was determined by analyzing specimens
      from a marijuana user without hydrolysis, with base hydrolysis, with beta
      glucuronidase treatment, and hydrolysis using sulfatase only. Treatment with
      sodium hydroxide proved to be the most efficient hydrolytic procedure. Specimens
      collected over 48 h showed an average conjugation of over 64.5%. The specimens
      were also analyzed for the active component, tetrahydrocannabinol (THC), which
      was detected in the oral fluid, in most cases, for up to 24 h. Parent THC was not
      found to be glucuronide bound. Specimens were then subjected to commercially
      available immunoassays in order to determine their utility as screening
      procedures. The metabolite, THCA, was detected in all samples up to and including
      the specimen 48 h after smoking, using the more sensitive screening assay and two
      dimensional GC-MS. Moreover, proof that the THCA is conjugated in oral fluid
      minimizes concerns associated with passive inhalation.

PMID- 17555642
TI  - A simple and rapid method for the identification of zolpidem carboxylic acid in
      urine.
AB  - Zolpidem is a non-benzodiazepine hypnotic that has been implicated in both drug
      facilitated sexual assault and drink spiking. Detection of the drug in urine is
      extremely difficult because of its extensive metabolism. A method is presented
      for the detection and quantitation of zolpidem carboxylic acid (ZCA), the major
      urinary metabolite of zolpidem. The metabolite was extracted from urine at pH 4.5
      5.0 with chloroform/isopropanol alkylated with ethyl iodide and identified by gas
      chromatography-mass spectrometry in the selected ion-monitoring mode. Following a
      single ingestion of 10 mg zopidem, ZCA is detected for up to 72 h. The limit of
      detection is 2 ng/mL, with an overall recovery of 80%. Using this procedure,
      zolpidem was identified in two cases of alleged drug-facilitated sexual assault.

PMID- 17555643
TI  - Quantification of tricyclic antidepressants and monoamine oxidase inhibitors by
      high-performance liquid chromatography-tandem mass spectrometry in whole blood.
AB  - Here we describe a liquid chromatography-tandem mass spectrometry method for the
      blood determination of tricyclic antidepressant drugs (amitriptyline,
      clomipramine, trimipramine, and imipramine, doxepin, mianserin, maprotyline,
      dosulepine, amoxapine), their active metabolites (desipramine, nortriptyline,
      demethylclomipramine, and nordoxepin), and monoamine oxidase inhibitors
      (toloxatone and moclobemide). A nontricyclic antidepressant (viloxazine) and two
      other anxiolytic drugs (buspirone and hydroxyzine) that could be encountered in
      toxicology have been included to this method. After a liquid-liquid extraction
      from blood, the compounds and their internal standard (methylrisperidone) were
      eluted on a XTerra RP18 column with a gradient of acetonitrile/ammonium formate
      buffer 4 mmol/L (pH 3.2). They were then detected by electrospray ionization mass
      spectrometry with multiple reaction monitoring mode. The calibration curves were
      linear over the range 5-100 ng/mL. The limit of quantification was 2 ng/mL for
      each compound. The bias were lower than 10%. Intraday and interday precisions,
      expressed as variation coefficient, were lower than 13%. The extraction
      recoveries were between 60 and 80% except for moclobemide, viloxazine, and
      toloxatone (10-60%). This specific and sensitive method allows management of
      intoxication and is suitable for the routine determination of antidepressants in
      forensic investigation.

PMID- 17555644
TI  - Matrix effect and cross-reactivity of select amphetamine-type substances,
      designer analogues, and putrefactive amines using the Bio-Quant direct ELISA
      presumptive assays for amphetamine and methamphetamine.
AB  - The aim of this study was to evaluate the Bio-Quant Direct ELISA assays for
      amphetamine and methamphetamine in the routine presumptive screening of
      biological fluids. Standard concentration curves of the target analytes were
      assayed to assess sensitivity, and known concentrations of common amphetamine
      type substances (ephedrine, pseudoephedrine, phentermine), designer analogues
      (MDA, MDMA, MDEA, MBDB, PMA, 4-MTA, 2CB), and putrefactive amines
      (phenylethylamine, putrescine, tryptamine, tyramine) were analyzed to determine
      cross-reactivity. Results of the standard curve studies show the capacity of both
      Direct ELISA kits to confidently detect down to 3 ng/mL interday (PBS matrix; CVs
      6.3-15.5%). Cross-reactivity relative to that of 50 ng/mL preparations of the
      target compounds demonstrated that the Direct ELISA kit for amphetamine also
      detected MDA (282%), PMA (265%), 4-MTA (280%), and phentermine (61%), and the
      Direct ELISA for methamphetamine also assayed positive for MDMA (73%), MDEA
      (18%), pseudoephedrine (19%), MBDB (8%), and ephedrine (9%). Matrix studies
      demonstrated that both ELISA kits could be applied to screening of blood, urine,
      and saliva to a concentration of 6 ng/mL or lower. In conclusion, the Bio-Quant
      Direct ELISA kits for amphetamine and methamphetamine are fast and accurate and
      have demonstrated themselves to be useful tools in routine toxicological testing.

PMID- 17555645
TI  - Rapid quantification of buprenorphine-glucuronide and norbuprenorphine
      glucuronide in human urine by LC-MS-MS.
AB  - A liquid chromatography-tandem mass spectrometry (LC-MS-MS) method was developed
      and validated for the determination of buprenorphine-glucuronide (BUP-G) and
      norbuprenorphine-glucuronide (NBUP-G) in human urine. The method included a
      dilution step followed by filtration through a Mini-Uniprep Filter and direct
      injection onto the LC column. The analytes were quantified in multiple reactions
      monitoring mode using one transition ion. Norbuprenorpine-d(3) (NBUP-d(3)) was
      used as the internal standard. The concentration ranges were 6-161 ng/mL for BUP
      G and 12-295 ng/mL for NBUP-G. Recoveries determined after filtration for the
      analytes were 75%. The between-day precision of the method was in the range of
      4.8-11%. The limits of quantification were found to be 4.6 ng/mL for BUP-G and
      11.8 ng/mL for NBUP-G. Approximately 1000 samples from law enforcement, prison
      inmates, probation services, and hospitals were analyzed by the presented method.
      The ratios of drug glucuronides versus creatinine were calculated for a selection
      of samples (n = 151), where there was information on treatment with buprenorphine
      between 16 and 20 mg/day. The majority (86%) of the samples had a ratio of BUP
      G/creatinine below 570 microg/g, and 76% of the samples had NBUP-G/creatinine
      lower than 1060 microg/g. The LC-MS-MS method proved to be robust and specific
      for the determination of BUP-G and NBUP-G in urine.

PMID- 17555646
TI  - Formation of scopolamine from N-butyl-scopolammonium bromide in cigarettes.
AB  - Scopolamine (hyoscine) is a naturally occurring alkaloid found in solonacea, the
      so-called "night shade" plants. Therapeutic applications of scopolamine are in
      ophthalmology to cause mydriasis and for the prevention of motion sickness, among
      others. It is known to induce hallucinogenic effects at a high dose. The N-butyl
      bromide derivative of scopolamine, available commercially as Buscopan, is
      commonly used as an antispasmotic. The possibility of forming scopolamine from N
      butyl-scopolammonium bromide when burning cigarettes fortified with Buscopan was
      investigated based on a record of a prison inmate who claimed to experience
      hallucinations after smoking Buscopan. Liquid chromatography-tandem mass
      spectrometry in electrospray ionization mode was used to monitor the formation of
      scopolamine. Various series of eight cigarettes spiked with 10 mg of N-butyl
      scopolammonium bromide with and without filters and in different smoking modes
      were investigated. The smoke of the burning cigarettes, the ashes, and the filter
      were analyzed for the presence of scopolamine. Scopolamine was detected in all
      cases.

PMID- 17555647
TI  - Quantification of lorazepam and lormetazepam in human breast milk using GC-MS in
      the negative chemical ionization mode.
AB  - Lormetazepam (Loramet is a benzodiazepine mainly used as an hypnotic to treat
      insomnia. Lorazepam (Temesta) is used as an anxiolytic, tranquilizer, sedative,
      and anticonvulsant, and it is the major metabolite of lormetazepam. In this
      study, we designed a method to simultaneously detect and quantify these
      substances in human breast milk. Solid-phase extraction of 2 mL of milk was
      followed by derivatization with a trimethylsilyl reagent. Separation and
      detection was performed using gas chromatography coupled to mass spectrometry in
      the negative chemical ionization mode. Calibration curves were linear in the
      ranges of 10-200 and 1-20 ng/mL for lorazepam and lormetazepam, respectively.
      Limits of detection were estimated at 0.016 ng/mL for lormetazepam and 0.100
      ng/mL for lorazepam. Our method was applied to real case samples from a woman
      receiving both benzodiazepines. Lorazepam concentrations varied from 55.3 to
      123.1 ng/mL, and lormetazepam concentrations varied from 1.7 to 7.3 ng/mL.

PMID- 17555648
TI  - Dextromethorphan in Wisconsin drivers.
AB  - Dextromethorphan is a synthetic analogue of codeine used in hundreds of over-the
      counter medications for its antitussive effects. There have been numerous reports
      of dextromethorphan abuse by young adults. Dextromethorphan can produce
      psychoactive effects similar to that of marijuana, and higher doses will produce
      dissociative effects, including sensory enhancement and hallucinations. The
      Wisconsin State Laboratory of Hygiene examined data from blood samples submitted
      from January 1999 through December 2004 to determine the incidence of
      dextromethorphan in suspected impaired drivers. A total of 108 samples were found
      to be positive for dextromethorphan during this time. Dextromethorphan
      concentrations in these cases ranged from less than 5 to 1800 ng/mL (mean 207
      ng/mL), compared to an expected therapeutic concentration range of 0.5-5.9 ng/mL.
      Overall, the highest dextromethorphan concentrations observed were in males aged
      16-20 years. Ninety-six percent of the specimens included in this study were also
      found to be positive for drugs other than dextromethorphan. A review of police
      and drug recognition expert reports from several of these cases showed that
      dextromethorphan-impaired drivers exhibited poor psychomotor performance on
      standardized field sobriety tests, horizontal gaze nystagmus, vertical gaze
      nystagmus, and overall signs of central nervous system depression.

PMID- 17555649
TI  - Postmortem memantine concentrations.
AB  - Postmortem fluid and tissue concentrations of memantine (Namenda), a drug
      recently approved for the treatment of Alzheimer's Disease by the FDA, are
      reported in a suspicious death. In addition, memantine concentrations considered
      to be incidental findings in three other cases are included to aid in the
      interpretation in future toxicological investigations. Memantine was extracted
      from biological samples by a standard liquid-liquid basic drug method followed by
      analysis utilizing a gas chromatograph-mass spectrometer operated in SIM mode.
      Blood concentrations ranged from 0.03 to 1.8 mg/L, and the liver concentration
      was 6.1 mg/kg.

PMID- 17555650
TI  - Which antibiotic prophylaxis guidelines for infective endocarditis should
      Canadian dentists follow?

PMID- 17555651
TI  - Some current legal issues that may affect oral and maxillofacial radiology: part
      1. Basic principles in digital dental radiology.
AB  - Developments in oral and maxillofacial radiology affect almost every aspect of
      dentistry: some change the legal framework in which Canadian dentists practise;
      some re-emphasize established standards of care, such as the dental radiologist's
      mantra, ALARA (using a dose that is as low as reasonably achievable) and viewing
      images in reduced ambient lighting. Developments in the legislation that
      regulates the use of radiology, such as Health Canada"s Safety Code 30 for
      radiation safety in dentistry and the Healing Arts Radiation Protection Act, also
      affect the practice of dental radiology. Some technical developments, such as
      charge-coupled devices and photostimulatable phosphors, are already well-known to
      the profession. Teleradiology, currently used in hospitals, but unfamiliar to
      most dentists (especially those working in urban communities), may soon have an
      impact on dentistry when it is used for Canada"s electronic health record, now
      under development. In this first of 2 articles about dental digital technology,
      we discuss the legal impact of developments in oral and maxillofacial radiology
      on dental practice and patient care.

PMID- 17555652
TI  - A review of bisphosphonate-associated osteonecrosis of the jaws and its
      management.
AB  - Bisphosphonate-associated osteonecrosis (BON) may result in serious oral
      complications, such as osteomyelitis and chronic exposure of necrotic bone.
      Dentists must be familiar with this disorder and pay special attention to all
      patients on bisphosphonate therapy due to their defective osteoclast function and
      reduced osseous tissue vascularity, leading to impaired wound healing. The
      purpose of this paper is to review the history and pathogenesis of BON, discuss
      its differential diagnosis, provide guidance to dentists on possible measures to
      prevent BON and review the management of patients with BON.

PMID- 17555653
TI  - Autotransplantation of a supplemental premolar: a case report.
AB  - In this article, we describe the autotransplantation of a supplemental premolar
      to replace an extracted first permanent molar in a 12-year-old boy. Although the
      end results are not ideal due to the small size of the donor tooth, the esthetics
      and function of the dental arch are partly restored using a natural tooth rather
      than a prosthesis. This case report illustrates the usefulness of
      autotransplantation as a viable treatment option in children with missing
      permanent teeth.

PMID- 17555654
TI  - Oral soft tissue lipomas: a case series.
AB  - OBJECTIVE: Lipomas are relatively uncommon tumours in the oral cavity; only 1% to
      4% of cases occur at this site. In this study, we describe the clinical and
      histopathologic features of 6 cases of oral lipoma. MATERIALS AND METHODS:
      Between 1997 and 2005, the files for all cases of oral lipoma at the oral
      pathology division, University of Ribeirao Preto, Sao Paulo, Brazil, were
      retrieved for study. Clinical data were retrieved from patient records, and all
      cases were reviewed microscopically and classified. RESULTS: Of the 6 cases, 3
      occurred in males and 3 in females; their mean age was 50.2 years (range: 28-78
      years). Most cases affected the buccal mucosa and the mean size of the tumours
      was 3.0 cm (range: 1.5-5.0 cm). Microscopically, 4 cases were classified as
      lipoma, 1 as fibrolipoma and 1 as intramuscular or infiltrative lipoma. All cases
      had been treated by simple surgical excision and there had been no recurrence
      after a mean treatment time of 50.3 months (range: 8-72 months). CONCLUSION: Oral
      lipomas are uncommon tumours that predominantly affect the buccal mucosa and are
      associated with an excellent prognosis.

PMID- 17555655
TI  - Rapid relaxation--practical management of preoperative anxiety.
AB  - Rapid relaxation (RR) is a brief set of suggestions, given while applying topical
      anesthetic, to reduce anxiety during local anesthesia and subsequent dental
      treatment. RR is recommended for managing mild dental anxiety, which is almost
      universal. RR combines elements of hypnosis, meditation and good basic chairside
      manner. It is noninvasive, takes little additional time, and empowers patients by
      providing them with an attractive, immediate alternative to catastrophization. We
      have found that RR markedly improves the quality of the dental experience.

PMID- 17555656
TI  - [Evaluation and improvement of health care quality: people are not cars].

PMID- 17555657
TI  - [Pneumococcal vaccination in the over-65 population].

PMID- 17555658
TI  - [Priorities in health promotion according to primary care health professionals: a
      Delphi study].
AB  - OBJECTIVES: To find out the opinions of primary care professionals on prevention
      activities in clinical practice, as well as the perceived obstacles to carrying
      them out and ways of overcoming them. PARTICIPANTS: A total of 129 professionals
      participated, including primary care doctors, nurses, technicians, primary care
      service managers, and public health professionals. DESIGN: Delphi questionnaire
      sent by e-mail. SETTING: Primary care in Catalonia, Spain. MAIN MEASUREMENTS AND
      RESULTS: Two rounds were made with response rates of 48.9% and 67.4%,
      respectively. Convergence of over 40% was obtained in all the questions after the
      second round. The main problems for prevention in clinical practice were lack of
      time, lack of training and the attitudes of the professionals themselves towards
      prevention. To improve implementing prevention in the practice, the professionals
      pointed out, training in communication skills, advice methodology and the use of
      clinical practice guidelines. CONCLUSIONS: Health professionals pointed out some
      specific needs in training which could help to improve the inclusion of
      prevention activities. On the other hand, it was noted that the attitudes of the
      professionals themselves towards prevention need to be improved.

PMID- 17555659
TI  - [Commentary: health promotion and responsibility of professionals].

PMID- 17555660
TI  - [Stated theory of family doctors on their relationships with patients].
AB  - OBJECTIVE: To identify and analyse the "theory" expressed by family doctors on
      the essential features of an effective and functional doctor-patient relationship
      and on how to achieve one ("stated theory" of Argyris and Schon). DESIGN:
      Qualitative, based on discourse analysis. SETTING: Primary care. METHOD:
      Interviews recorded with 10 family doctors selected by intentional sampling that
      were then transcribed. The propositions in the discourses were identified and
      conceptual maps were constructed. An inductive analysis classified the questions
      and positions that emerged and identified similarities and differences between
      subjects. RESULTS: Confidence and absence of conflict were the main desirable
      features of the doctor-patient relationship. Patients with a "demanding" attitude
      and their dishonesty were the most quoted obstacles. Doctors accepted
      negotiation, but held a very limited view of patient participation. Differences
      were appreciated on distance, the biomedical versus psychosocial focus and health
      education. Doctors' communication skills and qualities were little cited.
      Technical terminology in this area appeared little in the discourses.
      CONCLUSIONS: Discourses highlighted "health consumerism" and revealed
      disagreements on distance in the relationship and the psycho-social approach.
      These points, which should be prioritised in training, along with education, can
      serve to define family doctors distinct professional orientations. Training
      methodology must bear in mind that experience dominates "stated theory" in this
      area.

PMID- 17555661
TI  - [Evolution of the consumption of toxic substances among the adolescents of an
      urban area (1997-2004)].
AB  - OBJECTIVES: To find the evolution of the consumption of alcohol, tobacco and
      other drugs among adolescents in an urban area. DESIGN: Descriptive, cross
      sectional study using a self-administered questionnaire. SETTING: Secondary
      school (middle-class urban area). PARTICIPANTS AND MEASUREMENTS: Six hundred and
      seventy-eight students took part in the years 1997, 2001, and 2004. MEASUREMENTS
      AND MAIN RESULTS: The questionnaire included questions on age, sex and
      consumption of toxic substances. The following figures are given in order of the
      year of study. We studied 172, 249, and 257 adolescents, with a mean age of 14
      (interval, 12-17) and equality of sexes. The proportion of adolescents with no
      consumption of toxic substances increased (21%+/-3.1%; 34%+/-3.0% 56%+/-3.1%;
      P<.001, chi2), basically because alcohol consumption dropped (58%+/-3.6%; 61%+/
      3.2%; 41%+/-3.1%; P<.001, chi2), although its weekend consumption increased
      (84%+/-2.6%; 85%+/-2.2%; 96%+/-1.2%; P<.05, chi2), especially of spirits. Tobacco
      consumption increased (12%+/-2.4%; 21%+/-2.3%; 29%+/-2.4%; P<.001, chi2) with a
      pattern of daily smoking (9%+/-0.6%; 34%+/-3.2%; 47%+/-3.1%; P<.01, chi2). The
      consumption of illegal rugs also increased (9%+/-0.6%; 24%+/-2.8%; 16%+/-2.4%;
      P<.001, chi2), with an intermittent pattern of consumption (87%+/-1.6%; 71%+/
      2.3%; 85%+/-1.8). Cannabis is the most used drug (>90%), cocaine use fell and
      design drug use increased. Age affected consumption, but sex did not.
      CONCLUSIONS: In the last 8 years the consumption of toxic substances among
      adolescents has dropped, mainly because of less alcohol consumption. However, new
      forms of consumption of alcohol and other illegal drugs, especially at weekends,
      emerged and daily consumption of tobacco increased.

PMID- 17555662
TI  - [Factors underlying psycho-social problems].
AB  - OBJECTIVE: To investigate personal and family variables involved in the
      appearance of psychosocial problems (PSP) and the role of stressful life events
      (SLE) and Social Network and Support in its genesis; and to construct a profile
      of a PSP patient. DESIGN: Transversal, descriptive study. SETTING: Almanjayar
      Health Centre, Granada, Spain. PARTICIPANTS: Three hundred fourteen patients over
      18 selected by systematic sampling in on-demand consultation. MAIN MEASUREMENTS:
      Every patient had an interview, filling in the GHQ-28 (with scores>or=8
      considered indicative of PSP), the family Apgar test (Family Function study), the
      Holmes-Rahe Social Readjustment Scale (SLE in the last year), the DUKE-UNC
      questionnaire (Social Support), and Social Network (number of people). The
      Structure and Stage of the Family Life Cycle, social-economic and cultural level,
      work and income were also determined. A descriptive analysis of each variable and
      its association with the GHQ-28 through the chi2 test were also conducted. To
      find what categories were associated independently with high scores on the GHQ, a
      multivariate analysis was carried out. RESULTS: Categories of age (between 30 and
      59 years old), gender (being a woman) and social-economic level (unskilled
      workers) entail greatest risk of PSP. Similarly, single-parent families,
      perception of family dysfunction, high levels of stress (OR=3.02; 95% CI, 1.76
      5.18), and low social support affect PSP. CONCLUSIONS: The profile of a PSP
      patient in our setting is of a middle-aged woman forming part of a single-parent
      and/or dysfunctional family, who has suffered major SLEs and has insufficient
      social support.

PMID- 17555664
TI  - [Cooperation between public health and clinical care in a context of change of
      use of the health system].

PMID- 17555663
TI  - [Experience of women who request voluntary abortion: relationship with their
      health care environment].
AB  - OBJECTIVE: To describe women's perception of health care after they decided to
      have a voluntary termination of pregnancy and their referral to the abortion
      clinic. DESIGN: Qualitative method, using semi-structured interviews carried out
      between April and June 2005. SETTING: Primary Health Care District of Seville,
      Spain. PARTICIPANTS: Women living in the city of Seville and attending subsidized
      abortion clinics. MAIN MEASUREMENTS: Thirty-six women of varying ages and
      educational level were interviewed. The interview studied the assessment and
      information given by health professionals, and accessibility and use of family
      planning services. The results were analysed and triangulated with other studies
      and experts in the field. MAIN RESULTS: Most of the women interviewed were
      satisfied with the health care provided. Occasionally they perceived a
      bureaucratic attitude from physicians, who transmitted their disapproval and lack
      of support for an abortion decision. There were important differences in the way
      they were referred to abortion clinics, and in the information given to the
      women. Older women opted for private care, because this accelerated procedures
      and protected their privacy. Most women did not use family planning services
      before the abortion decision, except for requesting contraception. CONCLUSIONS:
      The study found there is a need to reduce the variety of patterns of care for
      women requesting an abortion, to speed up the proceedings and to train family
      doctors in assessment and information delivered to women during the process.

PMID- 17555665
TI  - [Family medicine in Paraguay].

PMID- 17555666
TI  - [Modifications in asthma patients' knowledge of the use of inhalers].

PMID- 17555667
TI  - [Understanding of avian flu and change in habits because of it].

PMID- 17555668
TI  - [Self-monitoring of glucaemia (SMG): a non-randomised study with control].

PMID- 17555669
TI  - [The biopsychosocial model and the 'market of lemons'].

PMID- 17555670
TI  - [Early detection in primary care of food conduct disorder in adolescents].

PMID- 17555671
TI  - [Patient-oriented medicine: a therapeutic revolution].

PMID- 17555672
TI  - [Repair of surgical defects of the nasal pyramid].
AB  - The nose is an area commonly involved in dermatological surgery. Basal cell and
      squamous cell carcinoma frequently affect the nasal appendix and its adjacent
      structures. There is a broad repertoire of surgical techniques for the
      reconstruction of this area, including direct closure, local and distant flaps,
      and grafts. Small surgical defects may be repaired by direct closure or second
      intention healing but local flaps and skin grafts from appropriate donor sites
      are frequently required after excision of tumors. Flaps have substantial
      advantages over grafts because they have their own blood supply and their
      viability does not depend entirely on the vascular bed of the surgical defect.
      Flaps offer similar skin in terms of color, texture and photoaging. Local flaps
      are essentially classified in several types: advancement, rotation and
      transposition. In this review we mention and graphically illustrate the
      reconstruction procedures from our own experience.

PMID- 17555673
TI  - [Topical pimecrolimus and tacrolimus and the risk of cancer].
AB  - In this review the controversy regarding the association between topical
      pimecrolimus and tacrolimus and the development of tumors is unfolded. After
      reviewing the literature we conclude that, currently, there is no scientific
      evidence of an increased incidence of skin cancer, lymphomas or systemic
      immunosuppression in those patients that use or have used topical calcineurin
      inhibitors. Published studies lack adequate number of patients and/or the follow
      up time is short enough to conclude that topical use of calcineurin inhibitors
      might be associated with the reported cases of skin cancer and lymphoma.
      Nevertheless the possibility of long term cutaneous and/or systemic side effects
      cannot be excluded.

PMID- 17555674
TI  - [Teledermatology. Review of 917 teleconsults].
AB  - INTRODUCTION: Teledermatology is been currently introduced as a diagnostic tool
      in the daily practice of the dermatologist. Many published works regarding
      teleconsult show the high sensitivity and economic saving of this technique as a
      diagnostic method. MATERIAL AND METHODS: In this article we report our experience
      with nearly 1,000 teleconsults carried out in a period of two years, from October
      2004 to October 2006. RESULTS: The majority of the 917 teleconsults performed
      were for benign lesions, notably seborrheic keratosis in 201 cases; among
      malignant lesions actinic keratosis appeared in 161 cases and melanoma was
      diagnosed in 5 cases. Fifty-eight percent of teleconsults have been arranged for
      a face-to-face consult in order to perform adequate treatment, in 90 % of cases,
      or to confirm diagnosis or carry out complementary exams, in 10 % of cases.
      CONCLUSION: The image is the gold standard for dermatological diagnosis.
      Currently, digital phototography gives us such a high image quality that, based
      on our experience, it can be stated that a neoplastic lesion that cannot be
      diagnosed by a high quality digital image with the available technology, rarely
      could be diagnosed in a face-to-face consult without the aid of complementary
      exams.

PMID- 17555675
TI  - [Hidradenitis suppurativa. Response to treatment with infliximab].
AB  - INTRODUCTION: Hidradenitis suppurativa is a chronic inflammatory disease that
      runs in outbreaks with painful lesions, fistulas and scars in axillae, groins,
      buttocks, and perianal and submammary regions. Among multiple drug therapies
      available, infliximab, usually employed in dermatology to control psoriasis, has
      shown its efficacy in the past five years. PATIENTS AND METHOD: It is a
      prospective, observational study to determine the efficacy and safety of
      infliximab in the treatment of hidradenitis suppurativa. We selected three women
      with a history of hidradenitis suppurativa of more than 10 years, with
      involvement of at least two anatomic locations that was recalcitrant to
      conventional therapies. Each patient received infliximab at a dose of
      5mg/kg/infusion on weeks 0, 2, 6 and every 8 weeks thereafter. RESULTS: Two of
      the three patients showed mild to moderate improvement of their disease while the
      third patient did not improve. We can highlight the variability of the results
      observed in these three patients. Adverse effects were generally mild and well
      tolerated by the three patients. Despite this, two patients withdrew the therapy
      due to loss of efficacy in one case and the development of generalized arthalgias
      in the other case. CONCLUSIONS: Treatment of hidradenitis supurativa with
      infliximab constitutes a moderately useful alternative in some cases.

PMID- 17555676
TI  - [Evaluation of a school intervention program to modify sun exposure behaviour].
AB  - INTRODUCTION: Nonmelanoma skin cancer is the most prevalent and incident tumor in
      the world, being sun exposure the most important risk factor. Childhood and
      adolescence are the periods where sun exposure is greatest. An intervention to
      modify sun-related behaviours is essential for skin cancer prophylaxis. MATERIAL
      AND METHODS: We carried out a quasi-experimental study on a school population of
      Granada with ages ranging from 11-12 years. The control and study groups
      completed a questionnaire prior to the intervention with educational program and
      thereafter. We performed a random conglomerate sampling of 628 teenagers.
      Statistical analysis was carried out using the Mc Nemar and Wilcoxon tests.
      RESULTS: After the intervention, the study group showed marked improvement in the
      results concerning knowledge about sun exposure and skin (OR = 2.89), sun
      exposure and environment (OR = 2.23), and sun exposure and health (OR = 1.4) as
      well as in attitudes and healthy behaviour regarding sun exposure (OR = 4.2).
      This difference was statistically significant compared to the control group.
      CONCLUSIONS: 1. Before planning a campaign for primary prophylaxis of skin cancer
      it is necessary to know the information and knowledge of the target population.
      2. The risk of acute, intermittent sun exposure and the use of different means of
      photoprotection should be stressed. 3. In our study group the rate of sun burn
      has decreased.

PMID- 17555677
TI  - [Contact dermatitis by camphor present in a flushing solution].
AB  - We report a case of allergic contact dermatitis due to alcamphor present in a
      flushing solution used by a 58-year-old woman. It is the first case described in
      our Division of Allergy and the second one reported in the literature. Alcamphor
      is a chemical substance present in many products that may have been
      underestimated as the causative agent of contact allergic dermatitis as the
      allergen is not available in the standard patch test batteries.

PMID- 17555678
TI  - [Acquired lymphangiectases and breast cancer].
AB  - Acquired lymphangiectases represent superficial lymphatic dilatations caused by a
      wide range of processes. Many cases reported in the literature develop in
      patients with upper limb lymphedema secondary to mastectomy, radiotherapy,
      keloids or scleroderma. Clinically they consist of traslucent vesicles in a
      chronic lymphedematous area. Histologically they are characterized by the
      presence of dilated spaces with flattened endotelial cells in the papillary
      dermis. All these cases have a good prognosis and there have not been any reports
      of malignant transformation. We describe a 67-year-old woman that showed multiple
      papules along her left upper limb associated with lymphedema. She had undergone a
      mastectomy followed by radiotherapy fourteen years before due to a breast cancer.
      Laboratory and radiological exams were within normal limits. The cutaneous
      lesions showed characteristic clinical and histological features of
      lymphangiectases and they progressively resolve in several weeks without any
      treatment.

PMID- 17555679
TI  - [Malignant syphilis in an HIV-infected patient].
AB  - Patients with HIV infection may develop common diseases with atypical clinical
      features. HIV infection may change the classic clinical course of syphilis and
      increase the incidence of a subtype of secondary syphilis named malignant
      syphilis. A homosexual patient with HIV infection consulted us about a one-month
      history of general malaise and widespread cutaneous ulcerative lesions, some with
      thick hemorrhagic crusts. Serology for syphilis was positive at high titers.
      Based on clinical, histological and serological findings, a diagnosis of
      malignant syphilis was made and the patient started treatment with penicillin G
      benzathine with progressive resolution of lesions. Malignant syphilis is a rare
      subtype of secondary syphilis that presents special clinical and histological
      features and has been associated with several processes characterized by variable
      degrees of immunosuppression. It is necessary to take into account this entity
      among the possible diagnoses in HIV-infected patients with cutaneous lesions.

PMID- 17555680
TI  - [Granular parakeratosis].
AB  - Granular parakeratosis is a rare entity that results from an acquired disorder of
      keratinization. Clinically presents as dark erythematous plaques, occasionally
      pruritic, that usually involve the axilla and other intertriginous areas. The
      pathology is characteristic and consists of thickening of the stratum corneum
      with compact parakeratosis and retention of keratohyaline granules, whereas the
      stratum granulosum is preserved. The etiology is unknown although some factors
      such as irritating physical or chemical agents have been implicated. Treatment
      response is variable. We report a new case in a 50-year-old woman with brownish
      and hyperkeratotic plaques on both axillae, of two years duration, with a
      compatible pathology that showed a favorable response to tacalcitol.

PMID- 17555681
TI  - [Dermatomyositis and punctate porokeratotic keratoderma as paraneoplastic
      syndrome of ovarian carcinoma].
AB  - Dermatomyositis (DM) is a dermatomyopathy with a broad spectrum of features,
      defined by Bohan et al as an objective set of clinical and laboratory criteria.
      Dermatomyositis has been associated with extracutaneous neoplasias, especially
      with ovarian carcinoma. The term <<punctate keratoderma>> comprises a group of
      diseases with different etiologies characterized by small hyperkeratotic lesions
      usually scattered in palms and soles. Punctate porokeratotic keratoderma (PPK) is
      a type of punctate keratoderma mainly defined by its peculiar histological
      features, including the presence of cornoid lamella similar to the one observed
      in porokeratosis. Punctate porokeratotic keratoderma has been considered a
      sporadic disease although some rare paraneoplastic cases have been published. We
      report for the first time a case of dermatomyositis with typical features of
      punctate porokeratotic keratoderma, both as paraneoplastic presentation of
      ovarian carcinoma. Its paraneoplastic nature is clearly demonstrated by the
      clinical improvement observed following tumor excision.

PMID- 17555682
TI  - [Lichen planus with esophageal involvement].
AB  - Lichen planus is an inflammatory disease of unknown etiology which may affect the
      esophagus. Patients with esophageal lichen planus are usually elderly women. The
      most frequent symptoms are dysphagia and odynophagia. There is usually
      concomitant oral involvement in cases of esophageal lichen planus. Endoscopic
      findings include erosions, exudates and stenosis. Systemic steroids are the most
      effective therapy for these patients. We report a 68-year-old woman with oral,
      genital and submammary lesions of lichen planus of nine months duration, that
      referred dysphagia and odynophagia. The endoscopic study revealed white plaques
      and areas of friable mucosa without stenosis. Histological findings were not
      conclusive but excluded changes due to fungal or reflux esophagitis. Biopsy of
      oral and cutaneous lesions showed typical features of lichen planus. Treatment
      with systemic steroids significantly improved the symptoms.

PMID- 17555683
TI  - [Painful eruption in the right groin].

PMID- 17555684
TI  - [Hyperpigmented macule in gingival mucosa].

PMID- 17555685
TI  - [Yellow nail syndrome].

PMID- 17555686
TI  - [Radiotherapy-induced scalp angiosarcoma].

PMID- 17555687
TI  - [Classic disseminated histoplasmosis with cutaneous involvement].

PMID- 17555688
TI  - [Michel's transport medium for immunofluorescence].

PMID- 17555689
TI  - A report on dental anxiety levels in children undergoing nitrous oxide inhalation
      sedation and propofol target controlled infusion intravenous sedation.
AB  - AIM: To report on two separate child sedation cohorts; one undergoing propofol
      intravenous sedation (IVS) and the other, nitrous oxide inhalation sedation (IS)
      in respect to changes in dental anxiety and subject characteristics. STUDY
      DESIGN: The age, gender, level of social deprivation and amount of treatment
      performed and observed patient behaviour during treatment, using the Frankl and a
      VAS scale, were recorded for each subject. Anxiety questionnaires were completed
      before and after treatment. These were: - Modified Child Dental Anxiety Scale
      (MCDAS); Children's Fear Survey Schedule- Dental Subscale (CFSS-DS) and two
      Visual Analogue Scales (VAS). RESULTS AND STATISTICS: Participants (36) attended
      for treatment under IS and 40 attended for treatment under propofol IVS. The IVS
      cohort was older (p<0.01), by between 1.9 and 4.1 years and had more treatment [p
      = 0.015, 95% confidence interval for the difference between the cohort medians
      was (0, 3) units]. The two cohorts were closely matched in respect to pre
      operative anxiety as measured by the MCDAS and CFSS-DS scales. There were
      significant anxiety reductions within each cohort as measured by three of the
      scales: - MCDAS, CFSS-DS and VAS (1) (p< or = 0.001) but no significant change in
      the VAS (2) scores. When the two cohorts were compared, there was no significant
      difference in the reduction of the self-reported anxiety for any of the four
      scales (p>0.05). The observed behaviour was good for both cohorts. CONCLUSION:
      Propofol target-controlled intravenous sedation and nitrous oxide inhalation
      sedation were similarly efficacious at anxiety reduction in referred dentally
      anxious children. Subjects undergoing propofol IVS were older than those
      undergoing IS. Propofol TCI may offer the opportunity for more treatment at each
      visit. Further propofol TCI conscious sedation studies are required.

PMID- 17555690
TI  - Molar incisor hypomineralization: review and prevalence data from the study of
      primary school children in Kaunas/Lithuania.
AB  - AIMS: These were to determine the prevalence of MIH in a group of primary school
      children in Kaunas, Lithuania and to compare the prevalence of MIH in Lithuania
      with the prevalence in other countries using published data. METHODS: First
      permanent molars and all permanent incisors were examined in 1277 children, aged
      7 to 9 years and having at least one erupted permanent molar, for demarcated
      opacities, post-eruptive enamel breakdown, atypical restorations and extractions
      due to MIH, according to the criteria, provided by the EAPD experts. Examinations
      were performed by two calibrated observers (k=0.829). RESULTS: Of all the
      children 190 (14.9%) had hypomineralization defects in at least one index tooth,
      124 (9.7%) had at least one affected molar and were considered as having MIH.
      Only demarcated opacities were present in 68 (54.8%) of children with MIH, 35
      (28.2 %) had at least one tooth with breakdown, 21 (16.9%) had atypical
      restorations. No teeth had been extracted due to MIH. Children with 3-6 affected
      teeth were 3.5 times more likely to have enamel breakdown and/or atypical
      restorations when compared with the children having only one or two affected
      teeth. Of the 124 children with MIH 96 (77.4%) had lesions only in molars, 28
      (22.6%) had both - molars and incisors - affected. CONCLUSIONS: MIH was common
      among 7-9 years old Lithuanian children; majority of the affected children were
      affected mildly. Severity of the lesions was increasing with the number of
      affected teeth. Compared to the other studies MIH in Lithuania was moderately
      prevalent.

PMID- 17555691
TI  - Who accompanies children to a dental hospital appointment?
AB  - AIM: To determine who accompanies paediatric dental patients to their
      appointments, in a teaching hospital setting. STUDY DESIGN: Data were recorded
      prospectively for children attending the Paediatric Dentistry clinic of the
      Charles Clifford Dental Hospital, Sheffield, England, over 4 months which
      included two school holiday periods. The data were recorded on a standardised
      data collection sheet, which included age and gender of the patient; number/s of
      accompanying adults and children and their relationship to the patient; the
      appointment session and appointment type. RESULTS: A total of 394 paediatric
      dental visits were recorded. Patients were of a mean age of 10 (range 1-17
      years). Most visits were for treatment (44.7%) and review (39.8%), with a much
      smaller proportion being new patient assessments (8.9%) and emergency
      appointments (6.6%). The numbers of afternoon and morning sessions recorded were
      approximately similar and 35% of the visits were recorded in a school holiday
      day. The majority of patients attended with at least one parent (91.6%). A parent
      was most likely to attend a new patient assessment (97.1%) or review visit
      (94.3%). Parental presence was less likely for treatment (89%) and least likely
      for emergency visits (84%). Most patients attended with their mother (62.1%).
      Patients were less frequently accompanied by parents (13.1%), their father
      (12.1%) and one or both grandparents (4.3%). Smaller proportions were accompanied
      by older siblings, a step parent, other relatives or foster carers. Two patients
      attended unaccompanied. The time of day, or whether it was a school holiday
      period or not, did not influence parental presence or the numbers of adults
      accompanying patients. However the additional presence of other children (non
      patients) was more likely on morning sessions and during school holidays.
      STATISTICS: One way analysis of variance (ANOVA), an independent sample t-test or
      chi-squared tests were undertaken as appropriate to determine whether there were
      any significant differences in parental or child accompaniment according to the
      patient's age; gender; type of appointment or time of appointment. Significance
      levels were set at p<0.05. CONCLUSIONS: It was of concern that a parent was least
      likely to accompany a child for an emergency visit when a history and consent may
      assume the greatest importance.

PMID- 17555692
TI  - Calcium hydroxide vs mineral trioxide aggregates for partial pulpotomy of
      permanent molars with deep caries.
AB  - AIM: To prospectively compare the clinical success rate of partial pulpotomy
      treatment in permanent molars using calcium hydroxide (CH) and mineral trioxide
      aggregates (MTA) as pulp dressing agents. METHODS: Restorable permanent first
      molars (64) with carious pulp exposures were randomly assigned to two groups; CH
      and MTA. A standardized operative procedure was followed in both groups.
      Following isolation and caries removal, the exposed superficial pulp tissue
      layers were removed with a sterile flame shape diamond bur to a depth of 2-4 mm.
      Bleeding was controlled and pulp dressed with either a paste of non-setting
      Ca(OH)2 followed by a setting layer of Ca(OH)2, or with grey MTA. The dressing
      materials in both groups were then covered with a layer of light cured glass
      ionomer cement. The teeth were either restored using amalgam, or where grossly
      carious with preformed metal crowns. Patients were scheduled for follow-up at 3,
      6, 12 months and annually thereafter. RESULTS: There were 34 patients (17 males
      and 17 females) with 51 teeth available for evaluation. The age of patients at
      the time of restoration ranged between 6.8 to 13.3 years (mean of 10.3 +/- 1.8
      years). The follow-up period ranged from 25.4 to 45.6 months with an average of
      34.8 +/- 4.4 months. There was no statistically significant difference in the
      success rate of teeth treated with CH (91%) in comparison to teeth treated with
      MTA (93%). Radiographically, a hard tissue barrier under CH was noticed in 12
      (55%) teeth compared with 18 (64%) teeth under MTA (p=0.4). CONCLUSIONS: MTA has
      clinical success rate comparable to CH as a pulp dressing material for partial
      pulpotomy in permanent molars with carious exposures.

PMID- 17555693
TI  - Debridement could be a solution to promote healing of established oral mucositis
      in children.
AB  - AIM: The aim of the study was to present a novel approach to promote healing of
      established oral mucositis and to alleviate symptom clusters in a group of
      children who were on induction chemotherapy. STUDY DESIGN: A clinical prospective
      study. METHODS: Children (40) diagnosed with Grade 3 or 4 oral mucositis were
      randomly assigned into two groups: In Group I (n=20), accumulated debris on
      ulcerations was removed (debridement); In Group II (n=20), subjects had no
      debridement. The condition of oral lesions, speech, lips, teeth, saliva, gingiva,
      and swallowing ability were examined 3 x week during the study. All subjects
      received the same oral care regimen. They were well balanced in respect of age,
      the type of antineoplastic treatment, and the number. RESULTS: Debridement
      promoted resolution and decreased the severity of oral mucositis significantly.
      Thus, the subjects had less oral discomfort, pain, and nutritional difficulties.
      STATISTICS: The data were entered in the SPSS 13.0 program, and the tests used
      were Kolmogorov-Smirnov, Shapiro-Wilk, Mann-Whitney, and Spearman's correlation
      coefficient with a 5% significance level. CONCLUSION: Well-controlled,
      prospective clinical studies related to the management of established oral
      mucositis will lead to the development of potential interventions and improved
      patient care.

PMID- 17555694
TI  - A comparison of knowledge of local analgesia, pulp therapy and restoration of
      primary molar teeth amongst dental students, dentists and dental therapists
      within a dental hospital setting.
AB  - AIM: To gain an overview of knowledge of local analgesia, pulpal therapy and
      restorative procedures in the primary dentition amongst dental undergraduate
      students (DS), dental therapy students (DTS), recently-qualified dentists (QD)
      and dental therapists (DT), working within a Dental Hospital setting. STUDY
      DESIGN: A survey undertaken at Dundee Dental Hospital and School, NHS Tayside,
      United Kingdom to determine current knowledge regarding the use of local
      analgesia, pulp anatomy and pulp therapy techniques in addition to restoration of
      primary teeth. RESULTS: Data were available for 24 individuals (DS: 5; QD: 6;
      DTS: 8; DT: 5). Deficiencies in knowledge regarding the maximum safe dose for
      local analgesia, pulp canal anatomy, pulp therapy medicaments and the preparation
      required prior to placement of a pre-formed metal crown were noted in both
      student and staff groups. CONCLUSIONS: The knowledge of basic dental procedures
      for children amongst a group of dental students, student dental therapists and
      recently qualified dentists and dental therapists, was found to be imperfect.
      These findings indicate that more research is needed on the educational
      procedures used in the transfer of such knowledge and skills. Deficiencies in
      knowledge were identified in all areas assessed. Courses should be designed at
      both the pre- and postgraduate level to address and avoid such gaps in knowledge.

PMID- 17555695
TI  - Assessment of the accuracy of visual examination, bite-wing radiographs and
      DIAGNOdent on the diagnosis of occlusal caries.
AB  - AIM: This was to evaluate the accuracy of the different methods for diagnosing
      occlusal caries in vivo, and to compare their performance in primary and
      permanent teeth. STUDY DESIGN: Permanent teeth (199) and primary molars (65) with
      macroscopically intact occlusal surface, with caries lesions without cavitation
      (white spot) or with a darkened sulcus were selected. The teeth were examined by
      the following methods: visual inspection, bite-wing radiographs and DIAGNOdent.
      The validation method employed for asserting the existence of carious lesion was
      cavity preparation. RESULTS: When the total sample was taken into consideration,
      laser (DIAGNOdent) provided the highest accuracy (74.8%). Even when the total
      sample was stratified, the laser accuracy was still high for both primary (88.4%)
      and permanent molars (70.4%). Visual inspection also provided a high accuracy for
      primary teeth (83.9%). The chi-square test showed a statistically significant
      difference between permanent and primary teeth considering occlusal caries
      diagnosis (p=0.0001). The Kappa coefficient showed good inter-examiner
      reproducibility for all methods. McNemar test revealed that the degree of intra
      examiner agreement for visual inspection was lower than for the other methods.
      CONCLUSIONS: As visual inspection also showed a high degree of accuracy, the
      laser method should be used as a complementary method in doubtful cases.
      Diagnostic methods of occlusal caries, in general, are more efficient in
      deciduous than in permanent teeth.

PMID- 17555696
TI  - Dissolution of xylitol from a food supplement administered with a novel slow
      release pacifier: preliminary results.
AB  - AIM: The aim of the study was to monitor the pattern of release and salivary
      xylitol concentrations during sucking of a slow-release pacifier used to deliver
      a novel food supplement. METHODS: The food supplement tablet contained 300 mg
      xylitol and 0.5 x 10(10) colony-forming units of Bifidobacterium lactis Bb-12 (Bb
      12). The reference tablet contained 300 mg xylitol and was used by 10 adults
      (mean age 32 years) in the study. Whole saliva samples were collected with 2.5
      min intervals during pacifier sucking. The salivary xylitol concentrations were
      determined using an enzyme assay kit. RESULTS: All subjects showed salivary
      xylitol concentrations exceeding 1% at least at one collection point. The xylitol
      and xylitol-Bb-12 tablets showed similar dissolving with no clear concentration
      peaks (comparison of saliva collection times; p = 0.139). CONCLUSION: Xylitol
      released from the food supplement, delivered with the novel pacifier, may result
      in salivary xylitol concentrations high enough to inhibit mutans streptococci in
      vivo.

PMID- 17555697
TI  - Integrating faces, houses, motion, and action: spontaneous binding across ventral
      and dorsal processing streams.
AB  - Perceiving an event requires the integration of its features across numerous
      brain maps and modules. Visual object perception is thought to be mediated by a
      ventral processing stream running from occipital to inferotemporal cortex,
      whereas most spatial processing and action control is attributed to the dorsal
      stream connecting occipital, parietal, and frontal cortex. Here we show that
      integration operates not only on ventral features and objects, such as faces and
      houses, but also across ventral and dorsal pathways, binding faces and houses to
      motion and manual action. Furthermore, these bindings seem to persist over time,
      as they influenced performance on future task-relevant visual stimuli. This is
      reflected by longer reaction times for repeating one, but alternating other
      features in a sequence, compared to complete repetition or alternation of
      features. Our findings are inconsistent with the notion that the dorsal stream is
      operating exclusively online and has no access to memory.

PMID- 17555698
TI  - Coordination changes in a discrete multi-articular action as a function of
      practice.
AB  - This study investigated how novices re-organized motor system degrees of freedom
      when practicing a multi-articular discrete kicking task. Four male participants
      practiced a soccer chipping task to seven different target positions over 12
      sessions for 4 weeks. Data from each participant indicated changes in degrees of
      freedom involvement as a function of practice. Further, each participant showed a
      different progression of change in levels of joint involvement for hip, knee and
      ankle in the kicking limb. Cross-correlations between joints in the kicking limb
      also showed different pathways of coupling and de-coupling with practice.
      Performance outcome scores improved and variability of intra-limb coordination
      decreased as a consequence of practice for all participants. Angle-angle plots
      also showed qualitative changes in intra-limb coordination between early and late
      practice sessions. Evidence suggested that foot velocity at ball contact was
      functionally manipulated by participants when kicking to target positions with
      varying height and distance constraints. Referencing data to a model of learning
      [Newell, K. M. (1985). Coordination, control and skill. In: Goodman, D., Franks,
      I., & Wilberg, R.B. (Eds.), Differing perspectives in motor learning, memory, and
      control. Amsterdam: North-Holland, pp. 295-317] determined that progression
      through different stages of learning may not be sequential and could alternate
      between learning stages. The present study highlighted individual differences in
      acquisition of coordination and control of joint motion even under similar task
      constraints, showing how degeneracy in movement systems facilitates learning.

PMID- 17555699
TI  - Possible cardioprotective effect of angiotensin-converting enzyme inhibitors
      during treatment of American tegumentary leishmaniasis with meglumine
      antimoniate.
AB  - We conducted an observational retrospective study to identify factors associated
      with prolongation of corrected QT (QTc) interval during treatment of American
      tegumentary leishmaniasis with meglumine antimoniate. A group of 108 patients
      with normal ECG before treatment were included. Thirty-one patients (29%)
      developed increase of QTc interval beyond 0.44s in the second ECG performed after
      an average of (mean+/-S.D.) 12.6+/-4.9 days. After univariate and multivariate
      analysis, the age was associated with prolonged QTc interval, and the use of
      angiotensin-converting enzyme (ACE) inhibitors demonstrated a protective factor.
      These results identify elderly as a risk factor to develop prolonged QTc due to
      antimonial therapy (odds ratio: 1.1; 95% confidence interval: 1.01-1.12), and
      suggest that use of ACE inhibitors is a possible cardioprotective agent (odds
      ratio: 0.3; 95% confidence interval: 0.003-0.34). Further studies using
      prospective methodology are necessary to define the role of ACE inhibitors as
      prophylactic agent in high-risk patients.

PMID- 17555700
TI  - A preliminary study on determination of Aphanius chantrei's feeding behaviour on
      mosquito larvae.
AB  - In this study, Aphanius chantrei's behaviour of feeding on mosquito larvae has
      been determined under experimental conditions. In groups that have different
      sizes (first group 27 mm; second group 40 mm; third group 47 mm), larvae
      consumption has increased with length and weight. During daytime, average larvae
      consumption has been observed as 14.75 number fish(-1) in the first group, 55.13
      number fish(-1) in the second group and 122.88 number fish(-1) in the third
      group. During the night, average larvae consumption has been determined for each
      group as 14.87 number fish(-1), 18.00 number fish(-1) and 28.36 number fish(-1),
      respectively. The average daily larvae consumption was found out as 29.62 number
      fish(-1) in the first group, 73.12 number fish(-1) in the second group and 151.25
      number fish(-1) in the third group. The differences between the groups were
      statistically significant (p<0.05). This study has shown that Aphanius chantrei
      can be used in biological combat against mosquito instead of Gambusia spp.,
      depending on the presence of food (mosquito); it can also feed at night.

PMID- 17555701
TI  - Bubble dynamics during the non-isothermal degassing of liquids. Exploiting
      microgravity conditions.
AB  - This work reviews the up to date state of understanding of dynamic phenomena
      occurring when gas bubbles grow over submerged heated surfaces. Gas bubbles are
      produced on hot surfaces because the adjacent liquid layers become superheated
      causing local desorption of dissolved gases while the liquid far afield remains
      at low temperatures. Non-isothermal degassing is a very complex process combining
      heat and mass transport coupled with momentum exchange between the two phases.
      Difficulties due to buoyancy effects on gas bubbles as well as natural convection
      of hot liquid layers hindered its thorough investigation in terrestrial
      conditions and only recent microgravity data allowed serious progress to be made.
      To reduce the complexity, gas bubble growth on a heated wall was studied here
      separately from bubble lateral motion and coalescence. A complete mathematical
      formulation was provided but given the inability to solve the problem numerically
      with the present resources, a series of approximate solutions were attempted. The
      comparison between experimental observations and theoretical predictions revealed
      useful information regarding the governing mechanisms of bubble growth.

PMID- 17555702
TI  - Scintillation proximity assay for measuring uptake by the human drug transporters
      hOCT1, hOAT3, and hOATP1B1.
AB  - Increasing evidence suggests a key role of transport proteins in the
      pharmacokinetics of drugs. Within the solute carrier (SLC) family, various
      organic cation transporters (OCTs), organic anion transporters (OATs), and
      organic anion transporting polypeptides (OATPs) that interact with drug molecules
      have been identified. Traditionally, cellular uptake assays require multiple
      steps and provide low experimental throughput. We here demonstrate the use of a
      scintillation proximity approach to detect substrate uptake by human drug
      transporters in real time. HEK293 cells stably transfected with hOCT1, hOATP1B1,
      or hOAT3 were grown directly in Cytostar-T scintillating microplates. Confluent
      cell monolayers were incubated with 14C- or 3H-labeled transporter substrates.
      Cellular uptake brings the radioisotopes into proximity with the scintillation
      plate base. The resulting light emission signals were recorded on-line in a
      microplate scintillation counter. Results show time- and concentration-dependent
      uptake of 14C-tetraethylammonium, 3H-methylphenylpyridinium (HEK-hOCT1), 3H
      estradiol-17beta-D-glucuronide (HEK-hOATP1B1), and 3H-estrone-3-sulfate (HEK
      hOAT3), while no respective uptake was detected in empty vector-transfected
      cells. Km of 14C-tetraethylammonium and 3H-estrone-3-sulfate uptake and hOAT3
      inhibition by ibuprofen and furosemide were similar to conventional dish uptake
      studies. The scintillation proximity approach is high throughput, amenable to
      automation and allows for identification of SLC transporter substrates and
      inhibitors in a convenient and reliable fashion, suggesting its broad
      applicability in drug discovery.

PMID- 17555703
TI  - Membrane permeabilization and cell damage by ultrashort electric field shocks.
AB  - Mammalian cells exposed to electric field pulses of nanosecond duration (nsPEF;
      60-ns, 12 kV/cm) experienced a profound and long-lasting increase in passive
      electrical conductance (G(m)) of the cell membrane, probably caused by opening of
      stable conductance pores (CPs). The CPs were permeable to Cl(-) and alkali metal
      cations, but not to larger molecules such as propidium iodide (PI). CPs gradually
      resealed; the process took minutes and could be observed even in dialyzed cells
      and in ATP- and glucose-free solutions. Cells subjected to long nsPEF trains (up
      to 200 pulses) underwent severe and immediate necrotic transformation (cell
      swelling, blebbing, cytoplasm granulation), but remained impermeable to PI for at
      least 30-60 min after the exposure. Both G(m) increase after short nsPEF trains
      and necrotic changes after long nsPEF trains were cell type-dependent: they were
      much weaker in HeLa than in GH3 cells. La(3+) and Gd(3+) ions significantly
      inhibited the nsPEF-induced G(m) increase (probably by blocking the CPs), and
      effectively protected intensely exposed cells from developing necrosis. We
      conclude that plasma membrane permeabilization is the principal cause of necrotic
      transformation in nsPEF-exposed cells and probably contributes to other known
      nsPEF bioeffects.

PMID- 17555704
TI  - Trehalose preserves DDA/TDB liposomes and their adjuvant effect during freeze
      drying.
AB  - Disaccharides are well-known reagents to protect biostructures like proteins and
      phospholipid-based liposomes during freezing and drying. We have investigated the
      ability of the two disaccharides trehalose and sucrose to stabilize a novel, non
      phospholipid-based liposomal adjuvant composed of the cationic
      dimethyldioctadecylammonium (DDA) and trehalose 6,6'-dibehenate (TDB) upon freeze
      drying. The liposomes were freeze-dried using a human dose concentration
      containing 2.5 mg/ml DDA and 0.5 mg/ml TDB with varying concentrations of the two
      sugars. The influence on particle size upon rehydration was investigated using
      photon correlation spectroscopy (PCS) and the gel to fluid phase transition was
      examined by differential scanning calorimetry (DSC). Data revealed that
      concentrations above 211 mM trehalose protected and preserved DDA/TDB during
      freeze-drying, and the liposomes were readily rehydrated. Sucrose was less
      efficient as a stabilizer and had to be used in concentrations above 396 mM in
      order to obtain the same effect. Immunization of mice with the tuberculosis
      vaccine candidate Ag85B-ESAT-6 in combination with the trehalose stabilized
      adjuvant showed that freeze-dried DDA/TDB liposomes retained their ability to
      stimulate both a strong cell-mediated immune response and an antibody response.
      These findings show that trehalose at isotonic concentrations protects cationic
      DDA/TDB-liposomes during freeze-drying. Since this is not the case for liposomes
      based on DDA solely, we suggest that the protection is facilitated via direct
      interaction with the headgroup of TDB and a kosmotropic effect, whereas direct
      interaction with DDA plays a minor role.

PMID- 17555705
TI  - Biophysical analysis of the interaction of granulysin-derived peptides with
      enterobacterial endotoxins.
AB  - To combat infections by Gram-negative bacteria, it is not only necessary to kill
      the bacteria but also to neutralize pathogenicity factors such as endotoxin
      (lipopolysaccharide, LPS). The development of antimicrobial peptides based on
      mammalian endotoxin-binding proteins is a promising tool in the fight against
      bacterial infections, and septic shock syndrome. Here, synthetic peptides derived
      from granulysin (Gra-pep) were investigated in microbiological and biophysical
      assays to understand their interaction with LPS. We analyzed the influence of the
      binding of Gra-pep on (1) the acyl chain melting of the hydrophobic moiety of
      LPS, lipid A, by Fourier-transform spectroscopy, (2) the aggregate structure of
      LPS by small-angle X-ray scattering and cryo-transmission electron microscopy,
      and 3) the enthalpy change by isothermal titration calorimetry. In addition, the
      influence of Gra-pep on the incorporation of LPS and LPS-LBP (lipopolysaccharide
      binding protein) complexes into negatively charged liposomes was monitored. Our
      findings demonstrate a characteristic change in the aggregate structure of LPS
      into multilamellar stacks in the presence of Gra-pep, but little or no change of
      acyl chain fluidity. Neutralization of LPS by Gra-pep is not due to a scavenging
      effect in solution, but rather proceeds after incorporation into target
      membranes, suggesting a requisite membrane-bound step.

PMID- 17555706
TI  - Structural divergence among cannabinoids influences membrane dynamics: a 2H solid
      state NMR analysis.
AB  - Cannabinoids are compounds that can modulate neuronal functions and immune
      responses via their activity at the CB(1) receptor. We used (2)H NMR order
      parameters and relaxation rate determination to delineate the behavior of
      magnetically aligned phospholipid bilayers in the presence of several
      structurally distinct cannabinoid ligands. THC (Delta(9)-Tetrahydrocannabinol)
      and WIN-55,212-2 were found to lower the phase transition temperature of the DMPC
      and to destabilize their acyl chains leading to a lower average S(CD) (
      approximately 0.13), while methanandamide and CP-55,940 exhibited unusual
      properties within the lipid bilayer resulting in a greater average S(CD) (
      approximately 0.14) at the top of the phospholipid upper chain. The CB(1)
      antagonist AM281 had average S(CD) values that were higher than the pure DMPC
      lipids, indicating a stabilization of the lipid bilayer. R(1Z) versus |S(CD)|(2)
      plots indicated that the membrane fluidity is increased in the presence of THC
      and WIN-55,212-2. The interaction of CP-55,940 with a variety of zwitterionic and
      charged membranes was also assessed. The unusual effect of CP-55,940 was present
      only in bicelles composed of DMPC. These studies strongly suggest that
      cannabinoid action on the membrane depends upon membrane composition as well as
      the structure of the cannabinoid ligands.

PMID- 17555707
TI  - Evaluation of a cognitive behavioral group intervention program for spouses of
      stroke patients.
AB  - This study investigated the effectiveness of a cognitive behavioral group program
      for spouses of stroke patients. The program consists of 15 bi-monthly 112h
      sessions. The goal of the intervention is to reduce the prevalence of mental
      disorders and burnout among care-giving spouses of stroke patients. The sample
      (stroke patients and their spouses) consisted of one intervention group (n=38
      couples) and two different control conditions, those receiving informational
      support (n=35 couples) and those receiving standard care (n=51 couples). We used
      the following instruments to measure spouses' mental health and quality of life:
      Beck Anxiety Inventory (BAI), Beck Depression Inventory (BDI), WHO Quality of
      Life Questionnaire. Measurements were taken before the intervention (Time 1),
      directly following the intervention (Time 2) and 6 months after Time 2 (Time 3).
      Several regression analyses allowed for examination of the short-term and long
      term effects of the intervention. The spouses' participation in the intervention
      program was associated with significant short-term changes in care-giving
      spouses' quality of life and with long-term changes in their quality of life and
      depression. The presented multi-component intervention appears to have an
      immediate effect on care-giving spouses' quality of life. In contrast, the
      intervention-related changes in more resistant mental-health-related variables
      did not appear until after a latent stage in the later post-intervention phase.

PMID- 17555708
TI  - Vulnerability associations and symptoms of post-traumatic stress disorder in
      soldiers deployed to Iraq.
AB  - The purpose of this prospective study was to examine whether explicit and
      implicit vulnerability associations before and after trauma exposure predict the
      onset and persistence of post-traumatic stress disorder (PTSD) symptoms. The
      implicit association test (IAT) was modified to assess associations of self with
      vulnerability related cues. Dutch soldiers completed the IAT 6 weeks before being
      deployed to Iraq, and again 5 months upon return home. They also rated an
      explicit vulnerability scale. PTSD symptoms were assessed 5 and 15 months after
      deployment with a clinical interview and questionnaire. The results showed that
      (1) the pre-deployment vulnerability measures did not predict PTSD symptoms at 5
      months, (2) both explicit and implicit post-deployment vulnerability measures
      explained unique variance in concurrent PTSD symptoms, over and above pre
      existing neuroticism, and (3) only the explicit post-deployment vulnerability
      measure predicted unique variance in later PTSD symptoms (at 15 months), after
      controlling for earlier symptoms. This was no longer the case after controlling
      for neuroticism. The results suggest that strong implicit associations between
      the self and vulnerability are a consequence rather than a cause of PTSD
      symptoms.

PMID- 17555710
TI  - FRETcalc plugin for calculation of FRET in non-continuous intracellular
      compartments.
AB  - FRET has emerged as an important tool for studying intracellular processes and
      interactions between biomolecules. Intracellular donor and acceptor molecules are
      distributed in individual organelles that usually have complex non-continuous
      shape. Consequently, background pixels arising from fluorophore-free regions of
      the cell are proximal to FRET-positive pixels, leading to systemic errors in the
      estimated FRET values. This study introduces a new FRET(TH) algorithm for FRET
      estimation by acceptor photobleaching that separates the FRET-positive pixels
      from the background by applying user-defined thresholds for pixel selection. The
      FRET(TH) algorithm was validated by analysis of interactions between
      fluorescently tagged proteins in the endoplasmic reticulum using acquired and
      simulated images. The novel algorithm showed superior performance to the regular
      FRET calculation algorithm in acquired images and in most simulations. The
      developed algorithm was incorporated into the FRETcalc plugin for ImageJ program
      that enables user-defined choices of thresholds for calculation of FRET by
      acceptor photobleaching.

PMID- 17555709
TI  - Docking of alpha-cobratoxin suggests a basal conformation of the nicotinic
      receptor.
AB  - We investigate the interactions between the long chain alpha-cobratoxin (Cbtx)
      and the nicotinic acetylcholine receptor using a rigid body docking procedure.
      The method, (i) reproduces the binding of Cbtx to Lymnea acetylcholine-binding
      protein (AChBP); (ii) shows that most of the structures of AChBP obtained in the
      presence of antagonists are compatible with Cbtx binding; and (iii) reveals a
      complex between Cbtx and muscle nAChR that corresponds to the basal "resting"
      state conformation. The structures are made available for further understanding
      of the allosteric transitions of the nAChR as well as for drug design.

PMID- 17555711
TI  - Indomethacin decreases EP2 prostanoid receptor expression in colon cancer cells.
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs) can decrease the risk of colorectal
      cancer; however, it has not been established if this effect is solely through
      their ability to inhibit cyclooxygenase (COX). In this study the effects of
      indomethacin, a potent NSAID and nonselective COX inhibitor, was examined in
      LS174T human colon cancer cells. These cells were found to express EP2 prostanoid
      receptors, but not the EP1, EP3 or EP4 subtypes. Pretreatment of LS174T cells
      with indomethacin produced a complete inhibition of prostaglandin E(2) (PGE(2))
      stimulated cyclic AMP (cAMP) formation in a dose dependent manner with an IC(50)
      of 21 microM. Interestingly, the inhibition of PGE(2)-stimulated cAMP formation
      by indomethacin was accompanied by a decrease in EP2 mRNA expression and by a
      decrease in the whole cell specific binding of [(3)H]PGE(2). Thus, treatment of
      LS174T cells with indomethacin causes a down regulation of EP2 prostanoid
      receptors expression that may be independent of COX inhibition.

PMID- 17555712
TI  - Activation of androgen receptor by histone demethylases JMJD2A and JMJD2D.
AB  - The androgen receptor (AR) is a transcription factor that is pivotal for the
      development of prostate cancer. Here, we have identified two related histone
      demethylases, JMJD2A and JMJD2D, which form complexes with ligand-bound AR. We
      found that AR interacts through its ligand binding domain with JMJD2A and JMJD2D.
      On the other hand, JMJD2A utilizes its catalytic domain or C-terminus to bind to
      AR, and JMJD2D does so via its C-terminus. Further, overexpression of JMJD2A or D
      stimulates AR function and this is dependent on JMJD2 catalytic activity.
      Conversely, downregulation of JMJD2A, which is often overexpressed in prostate
      tumors, reduces basal transcription of the AR target gene, prostate-specific
      antigen, in LNCaP prostate cancer cells. Altogether, our data have identified a
      novel class of AR coactivators, whose (over)expression in prostate tumors could
      contribute to the constitutive activation of AR and thus to androgen-depletion
      independency of advanced prostate cancer cells.

PMID- 17555713
TI  - Role of galectin-3 in prion infections of the CNS.
AB  - Galectin-3 is a multi-functional protein and participates in mediating
      inflammatory reactions. The pronounced overexpression of galectin-3 in prion
      infected brain tissue prompted us to study the role of this protein in a murine
      prion model. Immunofluorescence double-labelling identified microglia as the
      major cell type expressing galectin-3. Ablation of galectin-3 did not affect
      PrP(Sc)-deposition and development of gliosis. However, galectin-3(-/-)-mice
      showed prolonged survival times upon intracerebral and peripheral scrapie
      infections. Moreover, protein levels of the lysosomal activation marker LAMP-2
      were markedly reduced in prion-infected galectin-3(-/-)-mice suggesting a role of
      galectin-3 in regulation of lysosomal functions. Lower mRNA levels of Beclin-1
      and Atg5 in prion-infected wild-type and galectin-3(-/-)-mice indicated an
      impairment of autophagy although autophagosome formation was unchanged. The
      results point towards a detrimental role of galectin-3 in prion infections of the
      CNS and suggest that endo-/lysosomal dysfunction in combination with reduced
      autophagy may contribute to disease development.

PMID- 17555714
TI  - Rudiment incisors survive and erupt as supernumerary teeth as a result of USAG-1
      abrogation.
AB  - The term "supernumerary teeth" describes production of more than the normal
      number of teeth in the primary or permanent dentitions. Their aetiology is not
      understood. Uterine sensitization associated gene-1 (USAG-1) is a BMP antagonist
      that plays important roles in the local regulation of BMP signaling by binding
      and neutralizing BMP activities, and also serves as a modulator of Wnt signaling.
      We report here that USAG-1 deficient mice have supernumerary teeth. The
      supernumerary maxillary incisor appears to form as a result of the successive
      development of the rudimentary upper incisor tooth. We confirmed that the USAG-1
      expression is localized to the epithelium and mesenchyme of the rudimentary
      maxillary incisor tooth organ formation. USAG-1 abrogation rescued apoptotic
      elimination of odontogenic mesenchymal cells. Based upon these results, we
      conclude that USAG-1 controls the number of teeth in the maxillary incisor region
      by regulating apoptosis.

PMID- 17555715
TI  - Opposing roles of PAK2 and PAK4 in synergistic induction of MUC5AC mucin by
      bacterium NTHi and EGF.
AB  - Mucin, a major component of mucus, plays a critical role in host mucosal defense
      response by participating in mucociliary clearance. However, if overproduced,
      overproduced mucus leads to airway mucus obstruction and conductive hearing loss.
      Despite extensive studies that focus on investigating how MUC5AC mucin is
      regulated by one inducer at a time, how MUC5AC is synergistically regulated by
      multiple factors remains unknown. Here we provide direct evidence for the first
      time that bacterial pathogen NTHi and human growth factor EGF synergize with each
      other to potently up-regulate MUC5AC mucin transcription. Moreover, activation of
      both p38 and ERK is required for synergistic induction of MUC5AC by NTHi and EGF.
      Finally, PAK2 and PAK4 are differentially involved in this synergistic induction
      of MUC5AC by acting upstream of p38 and ERK. Our studies bring novel insights
      into our understanding of synergistic regulation of MUC5AC mucin by both
      pathological and physiological inducers.

PMID- 17555716
TI  - Structural basis for the recognition between the regulatory particles Nas6 and
      Rpt3 of the yeast 26S proteasome.
AB  - The 26S proteasome-dependent protein degradation is an evolutionarily conserved
      process. The mammalian oncoprotein gankyrin, which associates with S6 of the
      proteasome, facilitates the degradation of pRb, and thus possibly acts as a
      bridging factor between the proteasome and its substrates. However, the mechanism
      of the proteasome-dependent protein degradation in yeast is poorly understood.
      Here, we report the tertiary structure of the complex between Nas6 and a C
      terminal domain of Rpt3, which are the yeast orthologues of gankyrin and S6,
      respectively. The concave region of Nas6 bound to the alpha-helical domain of
      Rpt3. The stable interaction between Nas6 and Rpt3 was mediated by intermolecular
      interactions composed of complementary charged patches. The recognition of Rpt3
      by Nas6 in the crystal suggests that Nas6 is indeed a subunit of the 26S
      proteasome. These results provide a structural basis for the association between
      Nas6 and the heterohexameric ATPase ring of the proteasome through Rpt3.

PMID- 17555717
TI  - The dysbindin gene (DTNBP1) is associated with methamphetamine psychosis.
AB  - BACKGROUND: The dysbindin (DTNBP1 [dystrobrevin-binding protein 1]) gene has
      repeatedly been shown to be associated with schizophrenia across diverse
      populations. One study also showed that risk haplotypes were shared with a
      bipolar disorder subgroup with psychotic episodes, but not with all cases. DTNBP1
      may confer susceptibility to psychotic symptoms in various psychiatric disorders
      besides schizophrenia. METHODS: Methamphetamine psychosis, the psychotic symptoms
      of which are close to those observed in schizophrenia, was investigated through a
      case (n = 197)-control (n = 243) association analyses of DTNBP1. RESULTS: DTNBP1
      showed significant associations with methamphetamine psychosis at polymorphisms
      of P1635 (rs3213207, p = .00003) and SNPA (rs2619538, p = .049) and the three
      locus haplotype of P1655 (rs2619539)-P1635-SNPA (permutation p = .0005). The C-A
      A haplotype, which was identical to the protective haplotype previously reported
      for schizophrenia and psychotic bipolar disorders, was a protective factor (p =
      .0013, odds ratio [OR] = .62, 95% confidence interval [CI] .51-.77) for
      methamphetamine psychosis. The C-G-T haplotype was a risk for methamphetamine
      psychosis (p = .0012, OR = 14.9, 95% CI 3.5-64.2). CONCLUSIONS: Our genetic
      evidence suggests that DTNBP1 is involved in psychotic liability not only for
      schizophrenia but also for other psychotic disorders, including substance-induced
      psychosis.

PMID- 17555718
TI  - Monoamine oxidase a, gender differences, and social exclusion: comment on
      "Eisenberger et al.".

PMID- 17555719
TI  - A retrospective fetal ultrasound study of brain size in autism.
AB  - BACKGROUND: Despite evidence of possible abnormalities during fetal development,
      no study to date has attempted to investigate fetal brain growth in autism. Fetal
      head circumference (HC) and biparietal diameter (BPD) are highly correlated with
      fetal brain volume and are measured on fetal ultrasounds. METHODS: We used
      retrospective fetal ultrasound data to examine fetal head and body size during
      midgestation in children later diagnosed with autism. Second trimester fetal
      ultrasounds were collected for 45 autistic subjects and 222 control subjects. The
      HC, BPD, abdominal circumference (AC), and femur length (FL) measurements were
      extracted from the ultrasound records and standardized. The standardized growth
      parameters and discrepancies between them were compared in autism and control
      subjects. RESULTS: The autism group did not differ significantly from control
      subjects on individual measures of standardized HC, BPD, AC, and FL. Fetal HC was
      normal in the autism group. Preliminary findings suggest a tendency for fetal BPD
      to be large relative to HC in the autism group. An index of fetal body size, AC
      was significantly decreased in multiplex compared with simplex autism, and HC
      showed a trend decrease. The rate of pyelectasis was increased and breech
      position decreased in the autism group. No lateral ventricle abnormalities were
      reported. CONCLUSIONS: This preliminary study suggests that fetal head
      circumference is not abnormal in autism. The preliminary findings identify a
      subtle disturbance in uniformity of fetal brain growth and in renal development
      in some autistic cases, and differences in fetal development between simplex and
      multiplex autism.

PMID- 17555721
TI  - Effects of D-cycloserine on extinction: consequences of prior exposure to
      imipramine.
AB  - BACKGROUND: D-cycloserine (DCS), a partial N-methyl-D-aspartate (NMDA) agonist,
      facilitates the extinction of conditioned fear in animals and promotes the
      efficacy of exposure-based therapies in humans. The current study examined
      whether pre-exposure to the antidepressant imipramine affects the enhancement of
      extinction by DCS. METHODS: Twenty-nine rats were pre-exposed to saline, DCS, or
      imipramine for 14 days. The next day they were given five noise-shock pairings.
      The day after training, rats received six extinction trials and were then
      injected with DCS. At test the following day, freezing elicited by the noise was
      measured. RESULTS: Rats pre-exposed to either DCS or imipramine exhibited more
      freezing at test than rats pre-exposed to saline. CONCLUSIONS: Chronic exposure
      to either DCS or imipramine prevents the facilitating effect of DCS on
      extinction. This result suggests that DCS may not effectively enhance loss of
      fear in patients who are also being treated with antidepressants.

PMID- 17555720
TI  - Unaffected family members and schizophrenia patients share brain structure
      patterns: a high-dimensional pattern classification study.
AB  - BACKGROUND: A number of studies have provided evidence for genetic modulation of
      brain structure in unaffected family members (FM) of schizophrenia patients using
      conventional volumetric analysis. High-dimensional pattern classification methods
      have been reported to have the capacity to determine subtle and spatially complex
      structural patterns that distinguish schizophrenia patients from healthy control
      subjects using standard magnetic resonance imaging. This study investigates
      whether such endophenotypic patterns are found in FM via similar image analysis
      approaches. METHODS: A high-dimensional pattern classifier was constructed from a
      group of 69 patients and 79 control subjects, via an analysis that identified a
      subtle and spatially complex pattern of reduced brain volumes. The constructed
      classifier was applied to examine brain structure of 30 FM. RESULTS: The
      classifier indicated that FM had highly overlapping structural profiles with
      those of patients. Moreover, an orbitofrontal region of relatively increased
      white matter was found to contribute significantly to the classification,
      indicating that white matter alterations, along with reductions of gray matter
      volumes, might be present in patients and unaffected FM. CONCLUSIONS: These
      findings provide evidence that high-dimensional pattern classification can
      identify complex and subtle structural endophenotypes that are shared by probands
      and their unaffected FM.

PMID- 17555722
TI  - Regarding "omega-3 fatty acids supplementation in children with autism: a double
      blind randomized, placebo-controlled pilot study".

PMID- 17555723
TI  - Effects of various K+ channel blockers on spontaneous glycine release at rat
      spinal neurons.
AB  - Molecular biology approaches have identified more than 70 different K+ channel
      genes that assemble to form diverse functional classes of K+ channels. Although
      functional K+ channels are present within presynaptic nerve endings, direct
      studies of their precise identity and function have been generally limited to
      large, specialized presynaptic terminals such as basket cell terminals and Calyx
      of Held. In the present study, therefore, we investigated the functional K+
      channel subtypes on the small glycinergic nerve endings (< 1 microm diameter)
      projecting to spinal sacral dorsal commissural nucleus (SDCN) neurons. In the
      presence of TTX, whole-cell patch recording of mIPSCs was made from mechanically
      dispersed SDCN neurons in which functional nerve endings remain attached.
      Glycinergic responses were isolated by blocking glutamatergic and GABAergic
      inputs with CNQX, AP5 and bicuculline. The K+ channel blockers, 4-AP, TEA, delta
      dendrotoxin, margatoxin, iberiotoxin, charybdotoxin and apamin, significantly
      increased 'spontaneous' mIPSC frequency without affecting mIPSC amplitude. The
      results suggest the existence of the following K+ channel subtypes on glycinergic
      nerve endings that are involved in regulating 'spontaneous' glycine release
      (mIPSCs): the Shaker-related K+ channels Kv1.1, Kv1.2, Kv1.3, Kv1.6 and Kv1.7 and
      the intracellular Ca2+ -sensitive K+ channels BKCa, IKCa and SKCa. Ca2+ channel
      blockers by themselves, including L-type (nifedipine), P/Q-type (omega-agatoxin
      IVA, AgTX) and N-type (omega-conotoxin GVIA, CgTX), did not alter the
      'spontaneous' mIPSC frequency or amplitude, but inhibited the increase of the
      mIPSC frequency evoked by 4-AP, indicating the participation of L-, P/Q- and N
      type Ca2+ channels regulating 'spontaneous' glycine release from the nerve
      terminals.

PMID- 17555724
TI  - Cellular thiol pools are responsible for sequestration of cytotoxic reactive
      aldehydes: central role of free cysteine and cysteamine.
AB  - Cellular thiol pools have been shown to be important in the regulation of the
      redox status of cells, providing a large antioxidant pool consisting of free
      thiols, thiols bound in the disulfide form and thiols bound to proteins. However,
      experimental studies with the thiol cysteamine and its disulfide cystamine have
      demonstrated dramatic cytoprotection in experimental models where antioxidants
      provide only minor protection. These data suggest that an alternate action of
      thiols is important in their cytoprotective actions. A common feature of the in
      vitro and in vivo models, where these thiol agents demonstrate cytoprotection, is
      the generation of cytotoxic aldehydes. We therefore studied the actions of
      cystamine, cysteamine and several reference thiol agents as cytoprotectants
      against cell death induced by increased "aldehyde load". We found that all the
      thiol agents examined provided dramatic protection against aldehyde-induced cell
      death in SN56 cholinergic neurons, under conditions in which acrolein induced
      100% cell death. With regard to mechanism of action, the reference thiols
      cysteine, N-acetylcysteine, 2-mercaptoethanesulfonic acid, mercapto
      propionyglycine, and cysteamine can directly sequester aldehydes. In addition,
      these thiols were all found to augment intracellular cysteine levels via
      disulfide interchange reactions. Cysteamine and cystamine also augmented basal
      intracellular cysteamine levels. Our data, for the first time, demonstrate the
      importance of intracellular thiols in sequestering toxic reactive aldehyde
      products of lipid peroxidation and polyamine metabolism. In addition it appears
      that pharmacological manipulation of intracellular thiol pools might offer a new
      approach in the design of neuroprotective drug candidates.

PMID- 17555725
TI  - Maternal isolation alters the expression of neural proteins during development:
      'Stroking' stimulation reverses these effects.
AB  - Rat pups reared apart from their siblings, mother, and nest environment in the
      'pup-in-a-cup' regime show many alterations in behavior reminiscent of the
      Institutional Inattention/Overactivity Syndrome that characterizes children whose
      first few months are spent in institutions. In this report, we compare mother
      reared (MR) and artificially reared (AR) male rats in concentrations and
      distributions of brain proteins that are involved in normal brain development.
      When assessed during the juvenile period and in adulthood, AR animals showed
      elevations in Neu-N (a neuronal marker) and in S-100 (an astrocyte marker) but
      reductions in synaptophysin (synapse protein), N-CAM (cell-adhesion molecule),
      GAP-43 (axon elongation protein), and BDNF (brain derived neurotrophic factor) in
      comparison to MR controls in many brain sites involved in attention, impulsivity,
      activity, and social behavior. Daily 'licking-like' stimulation provided to AR
      animals (AR-MAX) throughout early development that reverses many of the
      behavioral deficits, also reverses many of the isolation effects on brain
      proteins. Study 2 showed that elevations in the number of neurons in combination
      with decreases in functionality are associated with a reduction in neuronal
      pruning and apoptosis during the very early post-partum period in AR animals and
      their reversal through daily 'licking-like' stimulation.

PMID- 17555727
TI  - Distribution of collagen XVII in the human brain.
AB  - We have recently discovered collagen XVII to be present in neurons of the human
      central nervous system. Collagen XVII has previously been primarily studied in
      the field of dermatopathology since it is abundantly expressed in the skin,
      which, like the nervous system, is ectodermal in origin. A link between
      dermatopathological and neurological entities has been implied due to clinical
      case studies revealing an association between bullous pemphigoid and age-related
      neurodegenerative disorders. The objective of this study was to assess the
      distribution of collagen XVII in the human brain in relation to normal ageing.
      Post-mortem brain tissue was obtained from 11 neurologically unimpaired subjects
      who had died from cardiovascular causes at the age of 17 to 78 years. Collagen
      XVII expression in various neuroanatomical regions, representing essentially the
      entire human brain, was then assessed using immunohistochemistry. We found
      collagen XVII to be expressed widely in the brain and to be located primarily in
      the soma and proximal axons of neurons. In contrast, glial cells did not express
      collagen XVII. The expression varied strikingly between different neuroanatomical
      regions, being most notable in motor nuclei and Betz cells followed by pyramidal
      neurons. There was no correlation between collagen XVII expression and variables
      such as gender, age at death, post-mortem delay and fixation time whereas a mode
      of death leading to notable neuronal ischemia depleted the protein expression.
      Many neurodegenerative disorders display a specific pattern of neuroanatomical
      involvement, thus the regionally variable expression of collagen XVII offers new
      prospects for research.

PMID- 17555726
TI  - Strain rate-dependent induction of reactive astrogliosis and cell death in three
      dimensional neuronal-astrocytic co-cultures.
AB  - A mechanical insult to the brain drastically alters the microenvironment as
      specific cell types become reactive in an effort to sequester severely damaged
      tissue. Although injury-induced astrogliosis has been investigated, the
      relationship between well-defined biomechanical inputs and acute astrogliotic
      alterations is not well understood. We evaluated the effects of strain rate on
      cell death and astrogliosis using a three-dimensional (3-D) in vitro model of
      neurons and astrocytes within a bioactive matrix. At 21 days post-plating, co
      cultures were deformed to 0.50 shear strain at strain rates of 1, 10, or 30 s(
      1). We found that cell death and astrogliotic profiles varied differentially
      based on strain rate at 2 days post-insult. Significant cell death was observed
      after moderate (10 s(-1)) and high (30 s(-1)) rate deformation, but not after
      quasi-static (1 s(-1)) loading. The vast majority of cell death occurred in
      neurons, suggesting that these cells are more susceptible to high rate shear
      strains than astrocytes for the insult parameters used here. Injury-induced
      astrogliosis was compared to co-cultures treated with transforming growth factor
      beta, which induced robust astrocyte hypertrophy and increased glial fibrillary
      acidic protein (GFAP) and chondroitin sulfate proteoglycans (CSPGs). Quasi-static
      loading resulted in increased cell density and CSPG secretion. Moderate rate
      deformation increased cell density, GFAP reactivity, and hypertrophic process
      density. High rate deformation resulted in increased GFAP reactivity; however,
      other astrogliotic alterations were not observed at this time-point. These
      results demonstrate that the mode and degree of astrogliosis depend on rate of
      deformation, demonstrating astrogliotic augmentation at sub-lethal injury levels
      as well as levels inducing cell death.

PMID- 17555729
TI  - Regioselective synthesis of 6-S-alkyl and 6-S-glycosyl-6-thio-D-mannofuranose
      derivatives from 5,6-O-cyclic sulfate precursors.
AB  - C-6 opening of 5,6-cyclic sulfate derivatives of mannofuranose with a thiolate
      anion followed by acidic hydrolysis of the acyclic sulfate gave 6-S-alkyl
      derivatives in good yields (70-95%) and short reaction times (10-15min). This
      methodology was applied to the synthesis of methyl 2,3-O-isopropylidene-6-S
      (2,3,4,6-tetra-O-acetyl-beta-d-glucopyranosyl)-6-thio-alpha-d-mannofuranoside
      (70%), 2,3-O-isopropylidene-6-S-(2,3,4,6-tetra-O-acetyl-beta-d-glucopyranosyl)-6
      thio-alpha-d-mannofuranose (87%) and 2,3-O-isopropylidene-6-S-(1,2:3,4-di-O
      isopropylidene-alpha-d-galactopyranos-6-yl)-6-thio-alpha-d-mannofuranose (87%).

PMID- 17555728
TI  - Inhibition of opioid release in the rat spinal cord by serotonin 5-HT(1A)
      receptors.
AB  - Neurotransmitter receptors that inhibit the release of opioid peptides in the
      spinal cord may play an important role in modulating pain. Serotonin is an
      important neurotransmitter in bulbospinal descending pathways, and 5-HT(1)
      receptors have been shown to inhibit synaptic transmission. Our goal was to
      determine whether 5-HT(1A) receptors inhibit opioid release in the spinal cord.
      Opioid release was evoked from rat spinal cord slices by electrically stimulating
      one dorsal horn, and measured in situ through the internalization of micro-opioid
      receptors in dorsal horn neurons. Stimulation with 1000 square pulses at 500 Hz
      produced internalization in 60% of the mu-opioid receptor neurons in the
      stimulated dorsal horn, but not in the contralateral one. The selective 5-HT(1A)
      receptor agonist 8-hydroxy-2-dipropylaminotetralin (8-OH-DPAT) inhibited the
      evoked mu-opioid receptor internalization by about 50%, with an approximate
      IC(50) of 50 nM. The effect of 8-OH-DPAT was attributed to inhibition of opioid
      release and not of the receptor internalization process, because 8-OH-DPAT did
      not inhibit the internalization induced by incubating the slices with a micro
      opioid receptor agonist (endomorphin-2, 100 nM). The selective 5-HT(1A) receptor
      antagonist WAY100135 (10 microM) blocked the inhibition produced by 1 microM 8-OH
      DPAT. These results show that 5-HT(1A) receptors inhibit opioid release in the
      spinal dorsal horn, probably from a subpopulation of enkephalin-containing
      presynaptic terminals. Therefore, 5-HT(1A) receptors likely decrease the
      analgesia produced by endogenously released opioids.

PMID- 17555730
TI  - Crystal and molecular structure of octakis(6-bromo-6-deoxy)-gamma-cyclodextrin. A
      novel stacking of a distorted macrocycle.
AB  - Octakis(6-bromo-6-deoxy)cyclomaltooctaose, perbrominated gamma-cyclodextrin at
      the primary side, crystallises from methanol in a very unique manner. The
      macrocycles are quite distorted in contrast to their beta-cyclodextrin analogue,
      heptakis(6-bromo-6-deoxy)cyclomaltoheptaose. The two monomers, arranged head-to
      head, form a completely new kind of dimer by mutually entering into each other,
      both at the primary and the secondary sides. At the primary, hydrophobic side,
      they interact by Br...Br interactions and at the secondary, hydrophilic side, by
      direct H-bonds between hydroxylic groups. The short contacts of the Br atoms
      contribute to the macrocycle's distortion, which is considerable compared to the
      few available structures of gamma-CDs persubstituted at the primary side with
      bulkier and in some occasions charged substituents. Water and methanol molecules
      are entrapped in the cyclodextrin cavity, mostly in the area of the secondary
      hydroxylic groups connecting the macrocycles by indirect H-bonds. Thus the
      solvent molecules strengthen the association of the two monomers and contribute
      to the stabilisation of the cavity. The monomers stack along the a-axis and form
      columns that align in parallel lines along the same axis resulting in the
      formation of alternating hydrophobic and hydrophilic layers perpendicular to the
      a-axis resembling in this respect, the structure of the analogous perbrominated
      beta-cyclodextrin.

PMID- 17555731
TI  - DFT studies of the ionization of alpha and beta glycopyranosyl donors.
AB  - Current attempts at mimicking the transition states (TSs) of glycosyl processing
      enzymes (GPEs) that proceed through TSs with a high degree of oxacarbenium ion
      formation suffer from a paucity of data about the conformations of such
      oxacarbenium ions. Because TSs are maxima, the current models based on minimized
      structures may need some refinement. As part of studies directed at optimizing
      chemical glycosylation the ionization of 3,4,6-tri-O-acetyl-alpha/beta-D
      glucopyranosyl chlorides and triflates, 2,3,4,6-tetra-O-methyl-alpha/beta-D
      glucopyranosyl fluorides, chlorides and triflates, 2,3,4,6-tetra-O-methyl
      alpha/beta-D-mannopyranosyl fluorides, 2,3-di-O-methyl 4,6-O-benzylidene
      alpha/beta-D-mannopyranosyl triflates and 2,3-di-O-methyl 4,6-O-benzylidene
      alpha/beta-D-glucopyranosyl triflates was studied by a prototypic density
      functional theory (DFT) procedure. In all cases, the alpha-anomers ionized
      smoothly to 4H3 half chair conformations or adjacent envelopes. By contrast, all
      beta-anomers exhibited an abrupt conformational change before ionization was
      complete. The nature of the conformations sampled depends on both the leaving
      group and the protecting group. The methods presented can be readily adapted to
      the study of any GPE or chemical glycosylation and provide a method for initial
      evaluation of plausible TSs, which in turn can be used in mimetic design.

PMID- 17555732
TI  - Facile synthesis of cleistetroside-2, a partially acetylated oligorhamnoside from
      Cleistopholis glauca and patens.
AB  - A tetrasaccharide, dodecanyl 4-O-acetyl-alpha-l-rhamnopyranosyl-(1-->3)-2,4-di-O
      acetyl-alpha-l-rhamnopyranosyl-(1-->3)-4-O-acetyl-alpha-l-rhamnopyranosyl-(1-->4)
      alpha-l-rhamnopyranoside (cleistetroside-2), was synthesized via '2+2' convergent
      strategy. Sequential regioselective 3-O-glycosylation of isopropyl 1-thio-alpha-l
      rhamnopyranoside (4) with 4-O-acetyl-2,3-O-isopropylidene-alpha-l-rhamnopyranosyl
      trichloroacetimidate (8), and isopropyl 4-O-acetyl-2,3-O-isopropylidene-alpha-l
      rhamnopyranosyl-(1-->3)-2,4-di-O-acetyl-alpha-l-1-thio-rhamnopyranoside (10) with
      dodecanyl 4-O-acetyl-alpha-l-rhamnopyranosyl-(1-->4)-2,3-O-isopropylidene-alpha-l
      rhamnopyranoside (12), greatly facilitate the target availability.

PMID- 17555733
TI  - Synthesis of new polyether glycodendrons as oligosaccharide mimetics.
AB  - Divalent and tetravalent glycomimetics based on polyether glycodendrons have been
      prepared. The branched scaffolds were decorated with galactose moieties on one
      hand and were elaborated into new glycodendrons of a 'mixed' type on the other,
      carrying both galactose and mannose moieties as biologically important sugar
      epitopes. All synthesized glycodendrons possess a focal point that can be
      employed for further derivatization and functionalization.

PMID- 17555734
TI  - The influence of selected steroid hormones on the physicochemical behaviour of
      DPPC liposomes.
AB  - The physicochemical properties of DPPC (1,2-dipalmitoyl-sn-glycero-3
      phosphocholine) liposomes used for topical application are pharmaceutically
      important. Therefore the aim of our study was to establish rapid and efficient
      methods for the exact characterisation of the physicochemical properties of
      extruded DPPC liposomes containing low concentration (0.5%, w/w) of different,
      therapeutically interesting steroid hormones, named 17-beta-estradiol, cpa
      (cyproterone acetate) and finasteride. In a first step it could be shown that all
      drugs influenced the liposome size and changed the zeta potential compared to the
      placebo formulations. Our further analytical strategy was to use micro
      calorimetry and ATR-FTIR (Fourier transformed infrared spectroscopy), two
      powerful and non-destructive methods to confirm the drug incorporation into the
      liposomes by proving interactions between the phospholipids and the steroids.
      Thereby it was even possible to localize the location of interaction. The
      characteristic phase transition temperatures of the phospholipid were decreased
      by the hormones which was detected by micro-DSC (differential scanning
      calorimetry). The results of the ATR-FTIR measurements indicated shifts of the
      specific lipid peaks, the C=O stretching bands and PO(2)(-) antisymmetric double
      stretching band, in the gel and liquid crystalline phase. A polar as well as a
      non-polar interaction could be proven. It could be shown that the investigated
      steroid hormones changed the physical properties of the phospholipid bilayers.

PMID- 17555735
TI  - Preparation of DL-2,3,4-trihydroxybutylarsonic acid and dl-2,3-dihydroxybutane
      1,4-bis(arsonic acid): starting compounds for novel arsonolipids.
AB  - The reaction of DL-1,3-butadiene diepoxide and of DL-1,4-dibromo-2,3-butanediol
      with aqueous alkaline sodium arsenite, "Na(3)AsO(3)", gave mixtures of the title
      arsonic acids which can be separated by anion exchange resin. Characterization of
      by-products leads to a better understanding of these reactions. These compounds
      are valuable intermediates for the preparation of novel arsonic acids and
      bis(arsonic acids).

PMID- 17555737
TI  - Evaluation of HbA1c on the Roche COBAS Integra 800 closed tube system.
AB  - OBJECTIVES: Evaluate a new whole blood (WB) HbA1c immunoassay and system with
      closed tube sampling (CTS) capability. DESIGN AND METHODS: Compare the Tina-quant
      Haemoglobin A1c Gen.2 (A1C-2) application on the COBAS INTEGRA 800 (I800) and new
      I800 dedicated system with CTS capability to current Integra applications and a
      HbA1c method accurate with common haemoglobin (Hb) variants. RESULTS: CVs were <
      or =1.7%. Mean bias against National Glycohaemoglobin Standardization Program
      (NGSP) samples was 0.3 HbA1c %. Compared to the Hitachi Tina-quant(R) [a] HbA1c
      II (HbA1c II) assay (accurate with common Hb variants), mean bias was 0.04% and
      0.21% HbA1c at 6% and 9%, respectively, with Hb AS variants; and -0.01% and 0.26%
      HbA1c at 6% and 9%, respectively, with Hb AC variants. CONCLUSIONS: The Integra
      A1C-2 application is precise, accurate against NGSP-assigned samples and the Hb
      variants tested; and, the I800 dedicated system with CTS capability offers
      increased throughput and reduced sample handling.

PMID- 17555736
TI  - The S447X variant of lipoprotein lipase gene is associated with metabolic
      syndrome and lipid levels among Turks.
AB  - BACKGROUND: We evaluated the relationship of the lipoprotein lipase (LPL) S447X
      variant with serum lipid levels and the metabolic syndrome (MS) in the Turkish
      Adult Risk Factor (TARF) study. This is the first study examining this LPL
      variant in the Turkish population. METHODS: The sample comprised 1586 Turkish
      adults. Genotyping was performed using the Taqman allelic discrimination assay.
      RESULTS: The X447 allele frequency was 0.11 (95% CI: 0.10-0.12). X447 allele
      carriers had significantly higher levels of HDL-C, LDL-C and total cholesterol;
      and lower fasting glucose, when compared with the SS genotype in females. In men,
      no significant association with any parameters was seen. The genotypic impact of
      the S447X variant on lipid levels appears to be modulated by environmental
      factors, such as cigarette smoking in women. Logistic regression analysis
      demonstrated a significantly reduced likelihood for metabolic syndrome in female
      X447 allele carriers (p=0.04), after adjustment for age, cigarette smoking,
      alcohol usage and physical activity grade. CONCLUSIONS: In especially Turkish
      women, compared to non-carriers, carriers of the LPL X447 allele have higher
      levels of HDL-C, LDL-C and total cholesterol, and show a degree of protection
      against developing the metabolic syndrome.

PMID- 17555738
TI  - Effect of hypoalbuminemia on the increased serum cholesteryl ester transfer
      protein concentration in children with idiopathic nephrotic syndrome.
AB  - OBJECTIVES: To examine the alteration of cholesteryl ester transfer protein
      (CETP) mass with the regression of albumin level in childhood nephrotic syndrome
      (NS) in order to clarify the effect of albumin on CETP in NS. DESIGN AND METHODS:
      Serum concentrations of CETP, kidney parameters and lipid traits were determined
      in 110 children with idiopathic NS and 150 control subjects. Of the NS patients,
      69 children with an active phase formed group 1, and 41 in remission formed group
      2. RESULTS: Group 1 presented severe hypoalbuminemia and hyperlipidemia, while
      group 2 exhibited marked recovery in both serum albumin level and
      lipid/lipoprotein profile. CETP concentration was significantly higher in group 1
      (7.36+/-2.43 mg/L, compared with controls 3.38+/-1.83 mg/L, P<0.0001), and
      declined to within normal range in group 2 (2.91+/-1.77 mg/L). CETP concentration
      had a strong inverse correlation with serum albumin level (r=-0.688, P<0.0001) in
      NS patients. Furthermore, when multiple linear regression analysis was performed,
      in which albumin, proteinuria, lipid traits, and prednisone dose were treated as
      independent variables, albumin was the only variable showing a significant
      correlation with CETP in the NS patients (R(2)=0.587, beta=-0.475, P<0.0001).
      CONCLUSIONS: The results demonstrate that the decreased serum albumin level might
      be a main determinant of the increased CETP concentration in pediatric NS.

PMID- 17555739
TI  - Visuospatial priming of the mental number line.
AB  - It has been argued that numbers are spatially organized along a "mental number
      line" that facilitates left-hand responses to small numbers, and right-hand
      responses to large numbers. We hypothesized that whenever the representations of
      visual and numerical space are concurrently activated, interactions can occur
      between them, before response selection. A spatial prime is processed faster than
      a numerical target, and consistent with our hypothesis, we found that such a
      spatial prime affects non-spatial, verbal responses more when the prime follows a
      numerical target (backward priming) then when it precedes it (forward priming).
      This finding emerged both in a number-comparison and a parity judgment task, and
      cannot be ascribed to a "Spatial-Numerical Association of Response Codes"
      (SNARC). Contrary to some earlier claims, we therefore conclude that visuospatial
      numerical interactions do occur, even before response selection.

PMID- 17555740
TI  - Distinct roles of Fgf8, Foxi1, Dlx3b and Pax8/2 during otic vesicle induction and
      maintenance in medaka.
AB  - The development of the vertebrate inner ear is a complex process that has been
      investigated in several model organisms. In this work, we examined genetic
      interactions regulating early development of otic structures in medaka. We
      demonstrate that misexpression of Fgf8, Dlx3b and Foxi1 during early gastrulation
      is sufficient to produce ectopic otic vesicles. Combined misexpression strongly
      increases the appearance of this phenotype. By using a heat-inducible promoter we
      were furthermore able to separate the regulatory interactions among Fgf8, Foxi1,
      Dlx3b, Pax8 and Pax2 genes, which are active during different stages of early
      otic development. In the preplacodal stage we suggest a central position of Foxi1
      within a regulatory network of early patterning genes including Dlx3b and Pax8.
      Different pathways are active after the placodal stage with Dlx3b playing a
      central role. There Dlx3b regulates members of the Pax-Six-Eya-Dach network and
      also strongly affects the early dorsoventral marker genes Otx1 and Gbx2.

PMID- 17555741
TI  - Foxi3 transcription factors and Notch signaling control the formation of skin
      ionocytes from epidermal precursors of the zebrafish embryo.
AB  - Ionocytes are specialized epithelial cell types involved in the maintenance of
      osmotic homeostasis. In amniotes, they are present in the renal system, while in
      water-living embryos of lower vertebrates additional ionocytes are found in the
      skin. Thus far, relatively little has been known about the mechanisms of ionocyte
      development. Here we demonstrate that skin ionocytes of zebrafish embryos derive
      from the same precursor cells as keratinocytes. Carrying out various combinations
      of gain- and loss-of-function studies, we show that the segregation of ionocytes
      from the epidermal epithelium is governed by an interplay between Notch signaling
      and two Forkhead-box transcription factors, Foxi3a and Foxi3b. The two foxi3
      genes are expressed in ionocyte precursors and are required both for ionocyte
      specific expression of the Notch ligand Jagged2a, and for ionocyte
      differentiation, characterized by the production of particular ATPases. Ionocytic
      Notch ligands, in turn, signal to neighboring cells, where activated Notch1 leads
      to a repression of foxi3 expression, allowing those cells to become
      keratinocytes. A model for ionocyte versus keratinocyte development will be
      presented, postulating additional thus far unidentified pro-ionocyte factors.

PMID- 17555742
TI  - Pre-emptive antinociceptive effects of a synthetic cannabinoid in a model of
      neuropathic pain.
AB  - The antinociceptive effects of WIN55,212-2, a synthetic cannabinoid, were
      evaluated in the model of partial sciatic nerve ligation after daily subcutaneous
      administration of 0.1 mg/kg a week before and two weeks after surgery. Mechanical
      allodynia and thermal hyperalgesia were evaluated in 46 rats allocated to
      receive: (1) Vehicle (before surgery)-Vehicle (after surgery); (2) Vehicle
      WIN55,212-2; (3) WIN55,212-2-Vehicle; (4) WIN55,212-2-WIN55,212-2; (5)
      AM251+vehicle; (6) AM251+WIN55,212-2; (7) AM630+vehicle; (8) AM630+WIN55,212-2;
      (9) Sham receiving vehicle; and (10) Sham receiving WIN55,212-2. The decreased in
      mechanical allodynia and thermal hyperalgesia by WIN55,212-2 was significantly
      greater when it was administered during one week before surgery. In conclusion,
      pre-emptive use of cannabinoids produced greater antinociceptive effects in a
      model of neuropathic pain and this effect is mediated by cannabinoid CB(1) and
      CB(2) receptors.

PMID- 17555744
TI  - A case control study of deep venous thrombosis in relation to factor V G1691A
      (Leiden) and A4070G (HR2 Haplotype) polymorphisms.
AB  - Activated protein C resistance (APCR) is a significant risk factor for venous
      thromboembolism (VTE), with the factor V (FV) G1691A (Leiden) mutation accounting
      for the majority of inherited APCR cases. An additional FV polymorphism, A4074G
      (FV-HR2), reportedly increased VTE risk by some, but not all groups. We
      determined the prevalence of FV-Leiden and FV-HR2 SNPs in 126 patients with deep
      venous thrombosis (DVT), and 197 control subjects. Frequencies of FV-Leiden A and
      HR2 G alleles, together with FV-Leiden G/A and A/A (but not HR2 A/G) genotypes
      were significantly higher among patients. While no significant linkage
      disequilibrium was noted between FV 1691A and 4070G or A alleles, significantly
      higher prevalence of single-mutant 1691G/4070G and 1691A/4070A haplotypes were
      seen in patients. FV Leiden and FV HR2 haplotype are independent risk factors for
      DVT, and their coinheritance does not seem to increase significantly DVT risk
      imparted by either.

PMID- 17555743
TI  - Cyclovirobuxine D ameliorates acute myocardial ischemia by K(ATP) channel
      opening, nitric oxide release and anti-thrombosis.
AB  - Cyclovirobuxine D is an active compound extracted from Buxus microphylla, which
      has been used for treating acute myocardial ischemia in China. The present study
      was to investigate its mechanism on myocardial ischemia. Cyclovirobuxine D
      significantly increased cardiomyocytes viability injured by oxidation or hypoxia.
      It significantly reduced the infarct size induced by ligating the coronary artery
      in rats, and the effect was almost abolished by glibenclamide, a blocker of ATP
      sensitive potassium channel, but it was not influenced by cyclooxygenase-2
      inhibitor celecoxib or estrogen receptor antagonist tamoxifen. In addition,
      cyclovirobuxine D significantly protected rat aorta endothelial cells against
      hypoxia and enhanced nitric oxide (NO) release from endothelial cells, which was
      inhibited by nitric oxide synthase (NOS) inhibitor N-nitro-L-arginine methyl
      ester (L-NAME). Furthermore, cyclovirobuxine D significantly decreased the weight
      of venous thrombus in rats. In conclusion, the action mechanism of
      cyclovirobuxine D on myocardial ischemia may be related with its cytoprotection,
      K(ATP) channel opening, NO generation stimulating and venous thrombosis
      inhibiting.

PMID- 17555745
TI  - HDAC inhibition amplifies gap junction communication in neural progenitors:
      potential for cell-mediated enzyme prodrug therapy.
AB  - Enzyme prodrug therapy using neural progenitor cells (NPCs) as delivery vehicles
      has been applied in animal models of gliomas and relies on gap junction
      communication (GJC) between delivery and target cells. This study investigated
      the effects of histone deacetylase (HDAC) inhibitors on GJC for the purpose of
      facilitating transfer of therapeutic molecules from recombinant NPCs. We studied
      a novel immortalized midbrain cell line, NGC-407 of embryonic human origin having
      neural precursor characteristics, as a potential delivery vehicle. The expression
      of gap junction protein connexin 43 (Cx43) was analyzed by western blot and
      immunocytochemistry. While Cx43 levels were decreased in untreated
      differentiating NGC-407 cells, the HDAC inhibitor 4-phenylbutyrate (4-PB)
      increased Cx43 expression along with increased membranous deposition in both
      proliferating and differentiating cells. Simultaneously, Ser 279/282
      phosphorylated form of Cx43 was declined in both culture conditions by 4-PB. The
      4-PB effect in NGC-407 cells was verified by using HNSC.100 human neural
      progenitors and Trichostatin A. Improved functional GJC is of imperative
      importance for therapeutic strategies involving intercellular transport of low
      molecular-weight compounds. We show here an enhancement by 4-PB, of the
      functional GJC among NGC-407 cells, as well as between NGC-407 and human glioma
      cells, as indicated by increased fluorescent dye transfer.

PMID- 17555747
TI  - FTY720-phosphate is dephosphorylated by lipid phosphate phosphatase 3.
AB  - FTY720 is a novel immunomodulatory drug efficacious in the treatment of multiple
      sclerosis. The drug is converted in vivo to the monophosphate, FTY720-P, by
      sphingosine kinase 2. This conversion is incomplete, suggesting opposing actions
      of kinase and phosphatase activities. To address which of the known lipid
      phosphatases might dephosphorylate FTY720-P, we overexpressed the broad
      specificity lipid phosphatases LPP1-3, and the specific S1P phosphatases (SPP1
      and 2) in HEK293 cells, and performed in vitro assays using lysates of
      transfected cells. Among LPPs, only LPP3 was able to dephosphorylate FTY720-P;
      among SPPs, only SPP1 showed activity against FTY720-P. On intact cells, LPP3
      acted as an ecto-phosphatase or FTY720-P, thus representing the major phosphatase
      involved in the equilibrium between FTY720 and FTY720-P observed in vivo.

PMID- 17555746
TI  - Molecular chaperones regulate p53 and suppress senescence programs.
AB  - Many types of cancer cells constitutively express major molecular chaperones at
      high levels. Recent findings demonstrate that specific depletion of individual
      chaperones, including various members of the Hsp70 family, small heat shock
      proteins, or VCP/p97, leads to activation of p53 pathway and subsequently
      triggers cellular senescence. Here, we discuss a possibility that in cancer cells
      high levels of chaperones serve to keep the p53 signaling under control, thus
      allowing cancer cells to evade the default senescence and form tumors.

PMID- 17555748
TI  - Isolation and characterization of nudC from mouse macrophages, a gene implicated
      in the inflammatory response through the regulation of PAF-AH(I) activity.
AB  - We report the characterization of a cDNA induced in mouse macrophages that
      encodes a 332-amino acid protein with extensive sequence identity with members of
      the mammalian nudC-like genes. The interaction between mNUDC and the regulatory
      beta subunit of platelet activating factor acetylhydrolase I (PAF-AH(I)) shown in
      this article indicates a new function of NUDC. Thus, we show that NUDC increases
      the catalytic activity of PAF-AH(I) and that this regulatory activity is located
      in the carboxyl terminal half of the protein which is highly conserved. This
      suggests a novel function for mammalian nudC-like genes as anti-inflammatory
      proteins.

PMID- 17555749
TI  - The hard cell: from proteomics to a whole cell model.
AB  - Proteomics has provided a wealth of data related to the nature of the proteome,
      including subcellular location, copy number, interaction partners and protein
      complexes. This raises the question of whether it is feasible to combine these
      data, together with other data related to overall cellular structure, to
      construct a static picture of the cell. In this minireview, we discuss these
      data, and the issues of turning them into whole cell models.

PMID- 17555750
TI  - Ovarian pregnancy after in vitro fertilization.
AB  - We report a rare ovarian pregnancy after in vitro fertilization and transcervical
      embryo transfer. Ultrasound guidance of embryo transfer does not eliminate the
      risk of this potentially lethal complication.

PMID- 17555751
TI  - Progesterone rise on the day of human chorionic gonadotropin administration
      impairs pregnancy outcome in day 3 single-embryo transfer, while has no effect on
      day 5 single blastocyst transfer.
AB  - Four hundred eighty-two patients undergoing single ET with GnRH-antagonist/recFSH
      protocol were analyzed. The incidence of premature luteinization (P above 1.5
      ng/mL on the day of hCG administration) was 18.2%. Even modest rises of P in the
      follicular phase have detrimental effect on the implantation potential of a good
      quality cleavage stage embryo. On the contrary, premature luteinization in the
      blastocyst subgroup had no effect on the pregnancy outcome.

PMID- 17555752
TI  - Peroxisome proliferator-activated receptor-gamma ligand reduced tumor necrosis
      factor-alpha-induced interleukin-8 production and growth in endometriotic stromal
      cells.
AB  - OBJECTIVE: To evaluate the influence of peroxisome proliferator-activated
      receptor-gamma (PPAR gamma) ligand (pioglitazone) on tumor necrosis factor-alpha
      (TNF-alpha)-induced interleukin-8 (IL-8) expression in endometriotic stromal
      cells (ESCs) and on proliferation of ESCs. DESIGN: Prospective study. SETTING:
      Department of Obstetrics and Gynecology, Tottori University Hospital, Yonago,
      Japan. PATIENT(S): Twenty-seven patients who underwent laparoscopic surgery.
      INTERVENTION(S): The ESCs were obtained from the chocolate cyst linings of
      ovaries. MAIN OUTCOME MEASURE(S): The expression of PPAR gamma gene and protein
      was determined by reverse transcriptase-polymerase chain reaction (RT-PCR) and
      immunocytochemistry. We determined the effect of pioglitazone on the production
      of TNF-alpha-induced IL-8 protein in culture supernatant of ESCs using ELISA. The
      effect of pioglitazone on TNF-alpha-induced proliferation of ESCs was evaluated
      by 5-bromo-2'-deoxyuridine proliferation assay. The activation of nuclear factor
      (NF)-kappaB in ESCs was evaluated by Western blot analyses and NF-kappaB
      transcription factor assays. RESULT(S): Immunocytochemistry and RT-PCR revealed
      the expression of PPAR gamma gene and protein in ESCs. The PPAR gamma protein was
      predominantly located in the cell nucleus. Measurement of IL-8 protein by ELISA
      showed that adding TNF-alpha (100 pg/mL) significantly increased IL-8 protein.
      Treating ESCs with 0.1-10 microM of pioglitazone significantly reduced the TNF
      alpha-induced IL-8 production. The presence of 0.1-10 microM of pioglitazone
      significantly suppressed growth of ESCs. The TNF-alpha increased the expression
      of phosphorylation of inhibitor kappaB (I kappaB). Adding pioglitazone (10
      microM) did not influence the expression of phosphorylated inhibitor kappaB (I
      kappaB). The TNF-alpha markedly increased the intranuclear concentration of p65,
      and adding pioglitazone (10 microM) significantly reduced the concentration of
      p65. CONCLUSION(S): The present study demonstrates for the first time that PPAR
      gamma is expressed in ESCs, and that pioglitazone reduced IL-8 secretion and the
      proliferation of ESCs. The PPAR gamma ligand may be an attractive therapeutic
      agent for endometriosis.

PMID- 17555753
TI  - Effect of oral D-penicillamine vs. colchicine on experimentally induced
      peritoneal adhesions in rats.
AB  - OBJECTIVE: To evaluate the effects of d-penicillamine on prevention or reduction
      of adhesion band formation and to compare its effects with those of colchicine in
      an animal model. DESIGN: A prospective experimental study. SETTING: Rats in an
      academic research environment. ANIMAL(S): Eighty female rats were randomly
      divided into four equal groups. In the end, group 4 was excluded because of high
      mortality rates. INTERVENTION(S): Adhesion bands were induced by intraperitoneal
      injection of 2.5 mL of a 10% sterile talc solution. The first group served as
      control, group 2 received oral D-penicillamine (35 mg/kg per day), group 3
      received oral colchicines (0.02 mg/kg per day), and group 4 received both drugs
      for 3 consecutive weeks. MAIN OUTCOME MEASURE(S): Formation of adhesion bands was
      quantitatively graded according to the Nair classification. RESULT(S): The
      proportion of control rats with substantial adhesion bands was significantly
      higher than that of rats in groups 2 or 3 (84.2%, 20%, and 33.3%). No difference
      regarding the grades of adhesion bands was found between the D-penicillamine and
      colchicine groups. CONCLUSION(S): Oral D-penicillamine is as effective as oral
      colchicine in prevention of peritoneal adhesion band formation in rats. Use of D
      penicillamine for this purpose should be weighed against its possible side
      effects.

PMID- 17555754
TI  - Are endometrial parameters by three-dimensional ultrasound and power Doppler
      angiography related to in vitro fertilization/embryo transfer outcome?
AB  - OBJECTIVE: To evaluate whether endometrial parameters by three-dimensional
      ultrasonography and power Doppler angiography (3D US-PDA) can predict in vitro
      fertilization/intracytoplasmic sperm injection (IVF/ICSI) outcome. DESIGN:
      Prospective clinical study. SETTING: Assisted reproduction unit in a referral
      hospital. PATIENT(S): Eighty women who underwent IVF cycles. INTERVENTION(S):
      Endometrial 3D US-PDA evaluated by VOCAL software (plane C and 9 degrees of
      rotational steps). MAIN OUTCOME MEASURE(S): Endometrial pattern, endometrial
      thickness (ET), endometrial volume (EV), and PDA indexes of vascularization index
      (VI), flow index (FI), and vascularization flow index (VFI) were measured on the
      day of human chorionic gonadotropin (hCG) administration. These measurements were
      related to IVF/ICSI and embryo transfer outcome. RESULT(S): In the pregnant
      group, EV, VI, FI, and FVI but not triple-line pattern and ET were statistically
      significantly higher. The area under receiver operating characteristic (ROC)
      curve was statistically significant for EV (0.746), VI (0.724), FI (0.828), and
      VFI (0.800) when no grade 1 embryos or only one were transferred (43 cycles, 14
      pregnancies) but not when two or three grade 1 embryos were transferred.
      Moreover, these parameters were statistically significant in predicting a normal
      pregnancy outcome (no early pregnancy loss) but were not related to multiple
      pregnancies. CONCLUSION(S): In IVF/ICSI cycles, 3D US-PDA is useful for
      evaluating endometrial receptivity. Endometrial volume and 3D power Doppler
      indexes are statistically significant in predicting the cycle outcome when one
      grade 1 or no grade 1 embryos are transferred, which could be helpful data in a
      single-embryo transfer policy.

PMID- 17555755
TI  - Early cleavage does not predict treatment outcome following the use of GnRH
      antagonists in women older than 35.
AB  - OBJECTIVE: To compare the early-cleavage rates and the implantation potential of
      embryos between the GnRH antagonist and agonist long stimulation protocols in
      women older than 35 years. DESIGN: Retrospective analysis. SETTING: Academic
      medical center. PATIENTS: Two hundred twenty patients older than 35 years old
      underwent IVF. INTERVENTION(S): Sixty-eight patients received GnRH antagonist
      protocol (GnRH antagonist group) and 152 patients received GnRH agonist long
      stimulation protocol (GnRH agonist group). MAIN OUTCOME MEASURE(S): Early
      cleavage rate of zygotes, implantation rate, and pregnancy rate. RESULT(S): Early
      cleavage rate of zygotes was significantly lower in the GnRH antagonist group
      than agonist group (21.8% vs. 32.6%, P<.0001). In the GnRH antagonist group, the
      pregnancy rate was not significantly different between the early-cleavage and
      late-cleavage subgroups (40.0% vs. 47.4%). In the GnRH agonist group, the
      pregnancy rate was significantly higher in the early-cleavage subgroup than in
      the late-cleavage subgroup (61.0% vs. 29.8%, P<.0001). CONCLUSION(S): In women
      older than 35 years, the early-cleavage rate of zygotes is significantly lower in
      the GnRH antagonist group than the agonist group. Early-cleavage status of
      zygotes is not a reliable predictor for embryo implantation in patients receiving
      the GnRH antagonist protocol.

PMID- 17555756
TI  - Sex and estrous cycle differences in the display of conditioned defeat in Syrian
      hamsters.
AB  - We have reported that there is a sex difference in the behavioral response to
      social defeat in hamsters. While previously defeated male hamsters fail to
      display normal territorial aggression and instead produce submissive/defensive
      behavior, a phenomenon that we have termed conditioned defeat (CD), only a small
      portion of previously defeated females exhibit CD. In Experiment 1, we tested the
      hypothesis that CD varies over the estrous cycle and found that previously
      defeated female hamsters tested on diestrus 2 and proestrus were more likely to
      exhibit CD than were females tested on diestrus 1 and estrus. In Experiment 2, we
      found that regardless of hormonal status, non-defeated females displayed normal
      territorial aggression, indicating that the behavioral changes observed in
      Experiment 1 were not due to a cyclic variation in submissive behavior
      independent of a previous defeat encounter. In Experiment 3, we found that
      females tested 4 days after defeat responded similarly to those tested 1 day
      after defeat suggesting that the hormonal status of females on the day of testing
      is a more important determinant of the behavioral response to defeat than is the
      hormonal status on the day of defeat training. Finally, in Experiment 4, we
      monitored anxiety-like behaviors in diestrous 1 and proestrous females in an open
      field arena and found that there was no effect of cycle on any of the observed
      behavioral measures, suggesting that the observed differences in CD are not the
      result of differences in generalized anxiety-like behaviors across the estrous
      cycle.

PMID- 17555757
TI  - National reviews of nursing: Challenges, corrections and cynicism. Response to
      Brooker (2007) 'The Chief Nursing Officer's review of mental health nursing in
      England an ode to 'motherhood and apple pie'?

PMID- 17555758
TI  - Impaired resistance in early secondary Nippostrongylus brasiliensis infections in
      mice with defective eosinophilopoeisis.
AB  - Eosinophils are an important feature of immune responses to infections with many
      of the tissue-invasive helminth parasites. The cytokine IL-5 and a high-affinity
      double GATA-binding site within the GATA-1 promoter are critical for
      eosinophilopoiesis. In this study, we believe we demonstrate for the first time
      that defects in eosinophilopoiesis are associated with impaired resistance to
      Nippostrongylus brasiliensis. Primary and secondary infections were established
      in wildtype (WT), IL-5(-/-) and DeltadblGATA mice. Resistance to secondary
      infections was impaired in IL-5(-/-) and DeltadblGATA mice, with significantly
      more larvae able to reach the lungs 2 days p.i. Pulmonary inflammation was
      minimal in all strains in the first 2 days of both primary and secondary
      infections, suggesting that eosinophil-dependent resistance occurred before
      larvae reached this site. Intestinal worm burdens and/or parasite egg production
      in primary infections were greater in animals with defective eosinophilopoiesis.
      While larvae did reach the gut by day 3 of secondary infections of WT and IL-5(-/
      ) mice, worms were expelled by day 7, even in the complete absence of eosinophils
      in tissues of the small intestine. This and our previous studies indicate that N.
      brasiliensis are likely to be exquisitely sensitive to attack by eosinophils soon
      after entry into the skin. Eosinophils in the gut may make a modest contribution
      to resistance on first exposure to the parasite, but are not required for
      expulsion in either primary or secondary infections. In order to mount an
      effective immune response it may be vital for the host to identify and attack the
      parasite before it implements immune evasion strategies and migrates to other
      anatomical sites. These observations may be of particular significance for the
      development of successful vaccines against hookworms and other nematodes.

PMID- 17555759
TI  - Residual platelet reactivity is associated with clinical and laboratory
      characteristics in patients with ischemic heart disease undergoing PCI on dual
      antiplatelet therapy.
AB  - A residual platelet reactivity (RPR) on antiplatelet therapy in patients with
      ischemic heart disease (IHD) has been reported to be associated with adverse
      clinical events by some Authors. However, scarce data are present on the clinical
      parameters associated with this phenomenon. No study, at our knowledge, was
      designed with the specific aim to examine the relationship between clinical
      characteristics and RPR. We sought to evaluate the clinical and laboratory
      characteristics associated with RPR in patients with IHD undergoing coronary
      revascularization on dual (aspirin plus clopidogrel) antiplatelet therapy. We
      included in the study 868 patients undergoing a coronary angiography: 386 with
      acute coronary syndromes undergoing a primary coronary revascularization and 482
      IHD patients scheduled to undergo an elective coronary angiography. We measured
      platelet function by both platelet aggregation with two agonists [0.5 mg/mL
      arachidonic acid (AA); 2 and 10 microM adenosine 5'-diphosphate (ADP)] and a
      point-of-care assay (PFA-100) on venous blood samples collected within 24 h from
      the end of the procedure. In patients with acute coronary syndromes and elective
      PCI diabetes is independently associated with RPR [group A: OR=2.9 (1.5-5.7) by
      10 microM ADP, OR=5.3 (1.1-27.8) by PFA-100; group B: OR=4.0 (1.6-10.0) by 10
      microM ADP]; reduced left ventricular systolic function [OR=3.7 (2.2-6.5) by AA
      PA, OR=2.7 (1.6-4.6) by PFA-100], chronic use of aspirin [OR=0.2 (0.1-0.4) by AA
      PA, OR=0.3 (0.2-0.5) by PFA-100] and loading dose of clopidogrel [OR=0.2 (0.06
      0.5) by 10 microM ADP] were independent variables significantly associated with
      RPR in patients undergoing elective PCI. In addition, inflammatory status was
      found to be significantly associated with RPR in both groups of patients. These
      results provide indications for the selection of patients for whom the evaluation
      of platelet reactivity could be useful.

PMID- 17555760
TI  - Calculating the 2-D motion of lumbar vertebrae using splines.

PMID- 17555761
TI  - Vaccination of newborns against hepatitis A in the presence of maternally derived
      antibodies.
AB  - Infection by hepatitis A virus (HAV) is a significant cause of childhood disease
      but effective vaccines are available. Naturally acquired anti-HAV antibodies
      ensure transfer of protective immunity which persists for up to 6 months in the
      newborn. Such maternal anti-HAV antibodies are able to inhibit the antibody
      responses in infants vaccinated with inactivated hepatitis A vaccines, although
      no clinically significant consequences of this are observed. By increasing the
      number of doses, for example by using a three dose primary vaccination schedule,
      and by increasing the amount of vaccinal antigen, this interfering effect may be
      partially overcome.

PMID- 17555762
TI  - An experimental comparison between rival theories of rapid automatized naming
      performance and its relationship to reading.
AB  - Two studies investigated the degree to which the relationship between rapid
      automatized naming (RAN) performance and reading development is driven by shared
      phonological processes. Study 1 assessed RAN, phonological awareness, and reading
      performance in 1010 7- to 10-year-olds. Results showed that RAN deficits occurred
      in the absence of phonological awareness deficits. These were accompanied by
      modest reading delays. In structural equation modeling, solutions where RAN was
      subsumed within a phonological processing factor did not provide a good fit to
      the data, suggesting that processes outside phonology may drive RAN performance
      and its association with reading. Study 2 investigated Kail's proposal that speed
      of processing underlies this relationship. Children with single RAN deficits
      showed slower speed of processing than did closely matched controls performing
      normally on RAN. However, regression analysis revealed that RAN made a unique
      contribution to reading even after accounting for processing speed. Theoretical
      implications are discussed.

PMID- 17555763
TI  - Effects of osmolytes on RNA secondary and tertiary structure stabilities and RNA
      Mg2+ interactions.
AB  - Osmolytes are small organic molecules accumulated by cells in response to osmotic
      stress. Although their effects on protein stability have been studied, there has
      been no systematic documentation of their influence on RNA. Here, the effects of
      nine osmolytes on the secondary and tertiary structure stabilities of six RNA
      structures of differing complexity and stability have been surveyed. Using
      thermal melting analysis, m-values (change in DeltaG degrees of RNA folding per
      molal concentration of osmolyte) have been measured. All the osmolytes
      destabilize RNA secondary structure, although to different extents, probably
      because they favor solubilization of base surfaces. Osmolyte effects on tertiary
      structure, however, can be either stabilizing or destabilizing. We hypothesize
      that the stabilizing osmolytes have unfavorable interactions with the RNA
      backbone, which becomes less accessible to solvent in most tertiary structures.
      Finally, it was found that as a larger fraction of the negative charge of an RNA
      tertiary structure is neutralized by hydrated Mg(2+), the RNA becomes less
      responsive to stabilizing osmolytes and may even be destabilized. The natural
      selection of osmolytes as protective agents must have been influenced by their
      effects on the stabilities of functional RNA structures, though in general, the
      effects of osmolytes on RNA and protein stabilities do not parallel each other.
      Our results also suggest that some osmolytes can be useful tools for studying
      intrinsically unstable RNA folds and assessing the mechanisms of Mg(2+)-induced
      RNA stabilization.

PMID- 17555764
TI  - Molecular basis for substrate-dependent transmembrane signaling in an outer
      membrane transporter.
AB  - Transmembrane signaling events that propagate through receptors and transporters
      have critical roles in cellular function and regulation. In the Escherichia coli
      vitamin B(12) transporter, BtuB, substrate binding to the extracellular surface
      of the protein triggers the unfolding of an energy coupling motif at the
      periplasmic surface. Here, the molecular interactions mediating this substrate
      dependent transmembrane signaling event were investigated in a novel way by
      combining a two mutant cycle analysis with site-directed spin labeling (SDSL).
      SDSL was used to monitor the unfolding and conformational equilibrium of the
      energy-coupling motif, and a thermodynamic two-mutant cycle analysis was used to
      estimate pair-wise interaction free energies for a pair of charged residues (D316
      and R14) within the protein interior. The data indicate that D316 and R14 are
      critical to this structural transition. Substrate binding is shown to reduce the
      interaction free energy between these residues, thereby triggering the unfolding
      of the energy coupling motif of this membrane transporter. The result indicates
      that SDSL when used in combination with a mutant cycle analysis provides an
      approach to examine the molecular interactions mediating signaling events in
      membrane proteins.

PMID- 17555765
TI  - The role of a hydrogen bonding network in the transmembrane beta-barrel OMPLA.
AB  - The hydrogen bonding of polar side-chains has emerged as an important theme for
      membrane protein interactions. The crystal structure of the dimeric state of the
      transmembrane beta-barrel protein outer membrane phospholipase A (OMPLA) revealed
      an intermolecular hydrogen bond mediated by a highly conserved glutamine side
      chain (Q94). It has been shown that the introduction of a polar residue can drive
      the association of model helices, and by extension it was presumed that the
      glutamine hydrogen bond played a key role in stabilizing the OMPLA dimer.
      However, a thermodynamic investigation using sedimentation equilibrium
      ultracentrifugation in detergent micelles reveals that the hydrogen bond plays
      only a very modest role in stabilizing the dimer. The Q94 side-chain is hydrogen
      bonded intramolecularly to residues Y92 and S96, but amino acid substitutions at
      these positions suggest these intramolecular interactions are not responsible for
      attenuating the strength of the intermolecular Q94 hydrogen bond. Other
      substitutions suggested that hydration of the local environment around Q94 may be
      responsible for the modest strength of the hydrogen bond. Heat inactivation
      experiments with the variants suggest that the Y92-Q94-S96 network may instead be
      important for thermal stability of the monomer. These results highlight the
      context dependence and broad range of interactions that can be mediated by polar
      residues in membrane proteins.

PMID- 17555766
TI  - The crystal structure of human cytosolic beta-glucosidase unravels the substrate
      aglycone specificity of a family 1 glycoside hydrolase.
AB  - Human cytosolic beta-glucosidase (hCBG) is a xenobiotic-metabolizing enzyme that
      hydrolyses certain flavonoid glucosides, with specificity depending on the
      aglycone moiety, the type of sugar and the linkage between them. In this study,
      the substrate preference of this enzyme was investigated by mutational analysis,
      X-ray crystallography and homology modelling. The crystal structure of hCBG was
      solved by the molecular replacement method and refined at 2.7 A resolution. The
      main-chain fold of the enzyme belongs to the (beta/alpha)(8) barrel structure,
      which is common to family 1 glycoside hydrolases. The active site is located at
      the bottom of a pocket (about 16 A deep) formed by large surface loops,
      surrounding the C termini of the barrel of beta-strands. As for all the clan of
      GH-A enzymes, the two catalytic glutamate residues are located on strand 4 (the
      acid/base Glu165) and on strand 7 (the nucleophile Glu373). Although many
      features of hCBG were shown to be very similar to previously described enzymes
      from this family, crucial differences were observed in the surface loops
      surrounding the aglycone binding site, and these are likely to strongly influence
      the substrate specificity. The positioning of a substrate molecule (quercetin-4'
      glucoside) by homology modelling revealed that hydrophobic interactions dominate
      the binding of the aglycone moiety. In particular, Val168, Trp345, Phe225,
      Phe179, Phe334 and Phe433 were identified as likely to be important in
      determining substrate specificity in hCBG, and site-directed mutagenesis
      supported a key role for some of these residues.

PMID- 17555768
TI  - Stochastic Gompertz model of tumour cell growth.
AB  - In this communication, based upon the deterministic Gompertz law of cell growth,
      a stochastic model in tumour growth is proposed. This model takes account of both
      cell fission and mortality too. The corresponding density function of the size of
      the tumour cells obeys a functional Fokker--Planck equation which can be solved
      analytically. It is found that the density function exhibits an interesting
      "multi-peak" structure generated by cell fission as time evolves. Within this
      framework the action of therapy is also examined by simply incorporating a
      therapy term into the deterministic cell growth term.

PMID- 17555767
TI  - The rate of TRAP binding to RNA is crucial for transcription attenuation control
      of the B. subtilis trp operon.
AB  - The trp RNA-binding attenuation protein (TRAP) regulates expression of the
      tryptophan biosynthetic and transport genes in Bacillus subtilis in response to
      changes in the levels of intracellular tryptophan. Transcription of the trpEDCFBA
      operon is controlled by an attenuation mechanism involving two overlapping RNA
      secondary structures in the 5' leader region of the trp transcript; TRAP binding
      promotes formation of a transcription terminator structure that halts
      transcription prior to the structural genes. TRAP consists of 11 identical
      subunits and is activated to bind RNA by binding up to 11 molecules of L
      tryptophan. The TRAP binding site in the leader region of the trp operon mRNA
      consists of 11 (G/U)AG repeats. We examined the importance of the rate of TRAP
      binding to RNA for the transcription attenuation mechanism. We compared the
      properties of two types of TRAP 11-mers: homo-11-mers composed of 11 wild-type
      subunits, and hetero-11-mers with only one wild-type subunit and ten mutant
      subunits defective in binding either RNA or tryptophan. The hetero-11-mers bound
      RNA with only slightly diminished equilibrium binding affinity but with slower on
      rates as compared to WT TRAP. The hetero-11-mers showed significantly decreased
      ability to induce transcription termination in the trp leader region when
      examined using an in vitro attenuation system. Together these results indicate
      that the rate of TRAP binding to RNA is a crucial factor in TRAP's ability to
      control attenuation.

PMID- 17555769
TI  - The influence of immune cross-reaction on phase structure in resonant solutions
      of a multi-strain seasonal SIR model.
AB  - Resonance in seasonally forced SIR epidemiological models may lead to stable
      solutions in which the epidemic period is an integer multiple of the forcing
      period. We examine the influence of immune cross-protection and cross-enhancement
      on the epidemic phase relationship of resonance solutions in an annually forced
      two-strain SIR model. Solutions with epidemics of the two strains in-phase
      commonly occur for wide ranges of cross-reaction intensity. Solutions with
      epidemics out-of-phase are less common and limited to narrow ranges of cross
      reaction intensity. This is broadly as predicted by the two natural periods of
      the system. The natural period corresponding to out-of-phase solutions is
      sensitive to changes in the cross-reaction parameter but the natural period
      corresponding to in-phase solutions is constant. Bifurcation analysis indicates
      that the stability of in-phase orbits is controlled by pitchfork and period
      doubling bifurcations while out-of-phase orbits may also be influenced by
      Andronov-Hopf bifurcations. In order to develop an intuitive understanding of the
      epidemiological factors governing the occurrence of different solutions we
      consider how the susceptible, infected and removed components of the system must
      interact to form a stable solution. This shows that the impact of cross-reaction
      is moderated by in-phase structures but amplified by out-of-phase structures.
      Although the average infection rate over long time periods is not affected by
      phase structure, this analysis indicates that in-phase epidemic patterns are
      likely to be more consistent and thus allow more effective health care
      management.

PMID- 17555770
TI  - Understanding diet-gene interactions: lessons from studying nutrigenomics and
      cardiovascular disease.
AB  - Socioeconomic development has resulted in an epidemiologic transition which has
      involved an increase in mortality and morbidity from chronic non-communicable
      diseases. Cardiovascular disease is one such disease. The rapidity with which
      this transition has occurred suggests that genetic factors are unlikely to be
      responsible. However, studies in twins suggest significant heritability for
      cardiovascular disease and its associated risk factors. We present data showing
      diet-gene interactions involving polymorphisms at the PPARA and PLIN loci. These
      data support the hypothesis that chronic diseases such as cardiovascular disease
      are a consequence of a complex interplay of genetic and environmental factors, of
      which diet plays an important role. They suggest that the effects of diet on
      chronic disease may be masked by heterogeneity of effect related to genetic
      variability between individuals and that consideration of diet-gene interactions
      may contribute to our understanding of the pathogenesis of cardiovascular
      disease. The identification of diet-gene interactions offers us an opportunity to
      develop dietary interventions that will obviate the effects of genetic factors on
      the risk of disease. In this way, we may be able to develop personalized dietary
      recommendations that optimize the outcome for the individual concerned.
      Nevertheless, while existing data points to the value of these studies,
      significant challenges need to be met to ensure that our conclusions are
      scientifically valid.

PMID- 17555771
TI  - Genetic variation in human disease and a new role for copy number variants.
AB  - While complex diseases, such as inflammatory bowel disease, do not follow
      distinctive Mendelian inheritance patterns, there is now considerable evidence
      from twin and pedigree studies to show that there are significant genetic
      influences in the development of many such diseases. In times past, this type of
      information was considered to be interesting, and was used mainly to alert other
      members of the families that they may also be at increased risk of developing the
      disease. However, with the ability to evaluate the genetic basis of common
      disease, this information will have important consequences for the diagnosis,
      prevention and treatment of the disorder. The genetic basis for common disease is
      likely to be more complicated than we had previously anticipated, since we now
      recognise epigenetic causes of disease, and other subtle gene regulatory
      mechanisms. Copy number variants have been highlighted in this review, as being a
      phenomenon that we have known about for a long time, but that has not previously
      been clearly associated with human disease. As complex disease is related to
      changes in gene expression, any variation in the human genome that alters gene
      expression is now a candidate for being involved in the disease process.

PMID- 17555772
TI  - Ethical, legal and social issues in nutrigenomics: the challenges of regulating
      service delivery and building health professional capacity.
AB  - Nutrigenomics, the conjunction of molecular nutrition with human genomics, is
      among the first publicly available applications of the human genome project.
      Nutrigenomics raises ethical, legal and social issues particularly with respect
      to how the public may access nutrigenetic tests and associated nutritional and
      lifestyle advice. Current regulatory controversy focuses on potential harms
      associated with direct-to-consumer (DTC) marketing of nutrigenetic tests and
      especially the need to protect consumers from unreliable tests, false claims and
      unproven dietary supplements. Nutrigenomics does, however, offer the potential of
      important health benefits for some individuals. The regulation of nutrigenomic
      services is slowly evolving, but there is little indication of increased
      professional capacity to support service delivery. Primary care physicians have
      minimal training in nutrition and genetics, and medical geneticists are in high
      demand and short supply. Dietetic practitioners are experts in nutrition science
      and interest in nutrigenomics is growing among members of this professional
      group. However, as with physicians, dietetics practitioners would require
      considerable training to bring nutrigenomics into their practice capacity. A
      downside of regulatory restrictions on direct consumer access to nutrigenomics
      companies is that responsible businesses may be hindered in meeting emergent
      public demand while health care professional groups have not yet developed
      capacity to provide nutrigenomics services.

PMID- 17555774
TI  - AMPAR exocytosis through NO modulation of PICK1.
AB  - The activation of NMDA receptors (NMDARs) triggers long-term changes in AMPA
      receptor-mediated synaptic transmission in the CNS. These long-lasting changes
      occur via the addition or removal of AMPA receptors (AMPARs) at the synaptic
      membrane and are mediated by a number of regulatory proteins including the GluR2
      AMPAR-interacting proteins n-ethylmaleimide sensitive factor (NSF) and Protein
      Interacting with C Kinase (PICK1). We have shown that the potent activation of
      NMDARs drives unclustering of PICK1 and PICK1-GluR2 dissociation in dendrites
      resulting in increased surface delivery of AMPARs. Here we show that the
      dispersal of PICK1 is mediated by the actions of NSF. We find that elevated NMDAR
      signaling leads to the S-nitrosylation of NSF and increased NSF-GluR2
      association. Both NMDAR-dependent unclustering of PICK1 and the delivery of
      surface AMPARs are dependent on release of nitric oxide (NO). Our data suggest
      that NMDAR activation can drive the surface delivery of AMPARs from a pool of
      intracellular AMPARs retained by PICK1 through the NO-dependent modification of
      NSF.

PMID- 17555773
TI  - Mus81 functions in the quality control of replication forks at the rDNA and is
      involved in the maintenance of rDNA repeat number in Saccharomyces cerevisiae.
AB  - Previous studies in yeast have suggested that the SGS1 DNA helicase or the Mus81
      Mms4 structure-specific endonuclease is required to suppress the accumulation of
      lethal recombination intermediates during DNA replication. However, the structure
      of these intermediates and their mechanism of the suppression are unknown. To
      examine this reaction, we have isolated and characterized a temperature-sensitive
      (ts) allele of MUS81. At the non-permissive temperature, sgs1Deltamus81(ts) cells
      arrest at G(2)/M phase after going through S-phase. Bulk DNA replication appears
      complete but is defective since the Rad53 checkpoint kinase is strongly
      phosphorylated under these conditions. In addition, the induction of Rad53 hyper
      phosphorylation by MMS was deficient at permissive temperature. Analysis of rDNA
      replication intermediates at the non-permissive temperature revealed elevated
      pausing of replication forks at the RFB in the sgs1Deltamus81(ts) mutant and a
      novel linear structure that was dependent on RAD52. Pulsed-field gel
      electrophoresis of the mus81Delta mutant revealed an expansion of the rDNA locus
      depending on RAD52, in addition to fragmentation of Chr XII in the
      sgs1Deltamus81(ts) mutant at permissive temperature. This is the first evidence
      that Mus81 functions in quality control of replication forks and that it is
      involved in the maintenance of rDNA repeats in vivo.

PMID- 17555775
TI  - Peripheral kinin B(1) and B(2) receptor-operated mechanisms are implicated in
      neuropathic nociception induced by spinal nerve ligation in rats.
AB  - The kinin system can contribute distinctly to the sensory changes associated with
      different models of nerve injury-induced neuropathic pain. This study examines
      the roles of kinin B(1) and B(2) receptor-operated mechanisms in alterations in
      nociceptive responses of rats submitted to unilateral L5/L6 spinal nerve ligation
      (SNL) injury. Behavioural responses to ipsilateral hind paw stimulation with
      acetone (evaporation-evoked cooling), radiant heat (Hargreaves method) or von
      Frey hairs revealed that SNL rats developed long-lasting cold allodynia (from
      Days 3 to 40 post-surgery, peak on Day 6), heat hyperalgesia (stable peak from
      Days 9 to 36) and tactile allodynia (stable peak from Days 3 to 51). SNL rats
      manifested nocifensive responses to intraplantar injections on Day 12 of the
      selective B(1) receptor agonist des-Arg(9)-bradykinin (DABK) and augmented
      responses to the selective B(2) receptor agonist bradykinin (BK; each at 0.01
      1nmol/paw). Systemic treatment of SNL rats with des-Arg(9)-Leu(8)-BK or HOE 140
      (peptidic B(1) and B(2) receptor antagonists, respectively; 0.1-1mumol/kg, i.p.)
      selectively blocked responses triggered by DABK and BK (1nmol/paw) and alleviated
      partially and transiently established cold allodynia, heat hyperalgesia and (to a
      lesser extent) tactile allodynia. Western blot analysis revealed enhanced
      expression of kinin B(1) and B(2) receptor protein in ipsilateral L4-L6 spinal
      nerve and hind paw skin samples collected on Day 12 after SNL surgery. These
      results indicate that peripheral pronociceptive kinin B(1) and B(2) receptor
      operated mechanisms contribute significantly to the maintenance of hind paw cold
      and mechanical allodynia and heat hyperalgesia induced by L5/L6 SNL in rats.

PMID- 17555776
TI  - First bite for hardness judgment as haptic exploratory procedure.
AB  - This study examines whether the modulation of biting behavior while subjects are
      engaged in food texture judgment can be explained as an intra-oral exploratory
      procedure optimized for recognizing a specified sensory attribute. Subjects were
      asked to compare two cheese samples for "the force required to penetrate the
      sample with the molar teeth" (the definition for "hardness" used in this study).
      Based on this definition, we hypothesize that the subjects targeted the first
      peak of the bite time-force profile (i.e. the intra-oral phenomenon of the
      initial fracture) as an essential property for judgment. We observed significant
      elongation of the first peak in the judgmental biting, compared to the biting
      without judgment, for all subjects. Shortening of the second peak (teeth-to-teeth
      contact) duration and decrease of the second peak force were also observed for
      all subjects. These active biting modulations suggested that the first peak was
      targeted for judgment, whereas the second peak was not targeted. The sample with
      greater maximum force or time-integral of the bite force at the first peak was
      also judged as requiring greater force; these agreements were statistically
      significant. This result confirmed that the parameters related to the first peak
      were targeted as judgmental cues. We concluded that the biting behavior in
      hardness judgment functions as the exploratory procedure and was optimized for
      encoding the target sensory properties.

PMID- 17555777
TI  - Hormonal induction of leptin resistance during pregnancy.
AB  - Despite elevated plasma leptin, food intake is increased during pregnancy leading
      to fat deposition. We have demonstrated that intracerebroventricular (icv) leptin
      is unable to suppress food intake in pregnant rats, as it does in non-pregnant
      animals. Hence, central leptin resistance develops during pregnancy. These
      changes are physiologically appropriate, providing increased energy reserves to
      help meet the high metabolic demands of fetal development and lactation. To
      characterise this central leptin resistance, we have measured levels of leptin
      receptor (Ob-Rb) mRNA in the hypothalamus, and examined leptin-induced
      phosphorylation of STAT3 (pSTAT3) in specific regions of the hypothalamus. In
      addition, to investigate the mechanism underlying pregnancy-induced leptin
      resistance, we have investigated effects of hormone treatments on hypothalamic
      responses to leptin in a pseudopregnant rat model. We observed a significant
      reduction of Ob-Rb mRNA levels in the ventromedial hypothalamic nucleus (VMH)
      during pregnancy, with no changes detected in other hypothalamic nuclei. Levels
      of leptin-induced pSTAT3 were specifically suppressed in the VMH and arcuate
      nucleus of pregnant rats compared to non-pregnant rats. Pseudopregnant rats were
      hyperphagic but did not become leptin resistant, suggesting that fetal or
      placental factors are required for the induction of leptin resistance. These data
      implicate the VMH as a key hypothalamic site involved in hormone-induced leptin
      resistance during pregnancy, and suggest that placental hormone secretion may
      mediate the hormone-induced loss of response to leptin.

PMID- 17555778
TI  - Non-invasive measurement of stress in dairy cows using infrared thermography.
AB  - The possibility that changes in eye temperature, measured using infrared
      thermography (IRT), can detect stress in dairy cattle was examined by six
      different stimulations of the stress axis. Six cows were given six treatments in
      a random Latin-square design: 1) Control (saline) 2) ACTH (0.05 mg Synacthen) 3)
      bCRH (20 mug) 4) bCRH (40 mug) 5) epinephrine (1.4 mug /kg liveweight) and 6)
      social isolation. Treatments were administered at time 0 and blood samples were
      taken at -30, -15, 0, 5, 10, 15, 20, 30, 40, 50, 60, 75, 90, 120, 180 and 240 min
      except for epinephrine which was sampled at -30, -15, -10, -5, 0, 2, 5, 10, 15,
      20, 30, 45, 60, 90 and 120 min. Core body temperature was recorded every 10 min
      and eye images collected every 2 min. Eye temperature and cortisol increased
      following catheterization (P<0.05). ACTH increased following bCRH, cortisol
      increased following ACTH and bCRH (P<0.001) and NEFA increased following
      epinephrine (P<0.001). Core body temperature was unaffected by treatments. Eye
      temperature was unaffected by CRH and epinephrine but was higher 30 and 60 min
      following control and ACTH (P<0.001). Our results provide evidence that exogenous
      HPA stimulation does not increase eye temperature. The increases in eye
      temperature following catheterization however raise the possibility that a
      cognitive component may be required for an eye temperature response to occur.

PMID- 17555779
TI  - Kinetic model of sucrose accumulation in maturing sugarcane culm tissue.
AB  - Biochemically, it is not completely understood why or how commercial varieties of
      sugarcane (Saccharum officinarum) are able to accumulate sucrose in high
      concentrations. Such concentrations are obtained despite the presence of sucrose
      synthesis/breakdown cycles (futile cycling) in the culm of the storage
      parenchyma. Given the complexity of the process, kinetic modelling may help to
      elucidate the factors governing sucrose accumulation or direct the design of
      experimental optimisation strategies. This paper describes the extension of an
      existing model of sucrose accumulation (Rohwer, J.M., Botha, F.C., 2001. Analysis
      of sucrose accumulation in the sugar cane culm on the basis of in vitro kinetic
      data. Biochem. J. 358, 437-445) to account for isoforms of sucrose synthase and
      fructokinase, carbon partitioning towards fibre formation, and the glycolytic
      enzymes phosphofructokinase (PFK), pyrophosphate-dependent PFK and aldolase.
      Moreover, by including data on the maximal activity of the enzymes as measured in
      different internodes, a growth model was constructed that describes the metabolic
      behaviour as sugarcane parenchymal tissue matures from internodes 3-10. While
      there was some discrepancy between modelled and experimentally determined steady
      state sucrose concentrations in the cytoplasm, steady-state fluxes showed a
      better fit. The model supports a hypothesis of vacuolar sucrose accumulation
      against a concentration gradient. A detailed metabolic control analysis of
      sucrose synthase showed that each isoform has a unique control profile. Fructose
      uptake by the cell and sucrose uptake by the vacuole had a negative control on
      the futile cycling of sucrose and a positive control on sucrose accumulation,
      while the control profile for neutral invertase was reversed. When the activities
      of these three enzymes were changed from their reference values, the effects on
      futile cycling and sucrose accumulation were amplified. The model can be run
      online at the JWS Online database (http://jjj.biochem.sun.ac.za/database/uys).

PMID- 17555780
TI  - Dynamic flux cartography of hairy roots primary metabolism.
AB  - A dynamic model for plant cell and hairy root primary metabolism is presented.
      The model includes nutrient uptake (Pi, sugars, nitrogen sources), the glycolysis
      and pentose phosphate pathways, the TCA cycle, amino acid biosynthesis,
      respiratory chain, biosynthesis of cell building blocks (structural hexoses,
      organic acids, lipids, and organic phosphated molecules). The energy shuttles
      (ATP, ADP) and cofactors (NAD/H, NADP/H) are also included. The model describes
      the kinetics of 44 biochemical reactions (fluxes) of the primary metabolism of
      plant cells and includes 41 biochemical species (metabolites, nutrients, biomass
      components). Multiple Michaelis-Menten type kinetics are used to describe
      biochemical reaction rates. Known regulatory phenomena on metabolic pathways are
      included using sigmoid switch functions. A visualization framework showing fluxes
      and metabolite concentrations over time is presented. The visualization of fluxes
      and metabolites is used to analyze simulation results from Catharanthus roseus
      hairy root 50 d batch cultures. The visualization of the metabolic system allows
      analyzing split ratios between pathways and flux time-variations. For carbon
      metabolism, the cells were observed to have relatively high and stable fluxes for
      the central carbon metabolism and low and variable fluxes for anabolic pathways.
      For phosphate metabolism, a very high free intracellular Pi turnover rate was
      observed with higher flux variations than for the carbon metabolism. Nitrogen
      metabolism also exhibited large flux variations. The potential uses of the model
      are also discussed.

PMID- 17555781
TI  - Hindsight: a re-analysis of the severe acute respiratory syndrome outbreak in
      Beijing.
AB  - OBJECTIVE: To review the severe acute respiratory syndrome (SARS) epidemic in
      Beijing using basic epidemiological principles omitted from the original
      analysis. STUDY DESIGN: Analysis of Prospective surveillance data for Beijing
      collected during the outbreak. METHODS: Surveillance data were reclassified
      according to World Health Organization criteria. Cases previously excluded
      without date of onset of illness were included in the epidemic curve from
      estimates using the average time between date of onset and date of
      hospitalization for cases with both dates. Cases who failed to give a contact
      history were now included; 7% (n=5) of cases during the import phase and 61%
      (n=365) during the peak phase. Previously excluded cases were included for
      plotting on an epidemic curve, and basic spot mapping for distribution of cases
      was used from attack rates recalculated for age, gender, occupation, residential
      location, date of onset of illness and demographics. RESULTS: The spot map
      effectively illustrated clusters by residency, with the inner-city sustaining the
      highest attack rate (33.42 per 100,000), followed by an easterly distribution 5
      30km away (21.62 per 10,000), and lowest in districts 60-160km away (9.21 per
      100,000). The new epidemic curve shows the outbreak commencing 10 days earlier
      than initially reported, with a three-fold greater increase in cases during the
      escalation phase than previously estimated. CONCLUSION: In hindsight, the
      investigation of the Beijing SARS would have benefited from the use of spot
      maping as an essential outbreak tool for early identification of specific
      geographical area(s) for quarantining. If a spot map of incidence density rates
      was used during the early phase of the outbreak, the inner city might have been
      identified as a major risk factor requiring rapid quarantining. Contact history
      became uncommon as the outbreak progressed, suggesting that hospitals were over
      burdened or pathogenesis and environment risk factors changed, strengthening the
      usefulness of early spot mapping and the need to modify risk factors included as
      contact history as the epidemic progresses.

PMID- 17555782
TI  - Missed appointments at a Swiss university outpatient clinic.
AB  - OBJECTIVE: To assess the appointment conditions and characteristics of patients
      who miss their appointments ('no-shows'); this will aid in the formulation of
      intervention methods to reduce no-show rates. METHODS: During a one-month period,
      data on all no-shows at the general internal medicine outpatient clinic of the
      Geneva University Hospitals were collected. Control patients were matched for
      appointment time and gender. Patient and appointment characteristics were
      collated on 13 parameters, and these were compared between no-shows and controls.
      RESULTS: Two hundred and six of 1296 appointments were no-shows (15.8%). Compared
      with controls, no-shows were younger, born earlier in the year, more often were
      not Europeans, more often had a common language with the physician or translator
      (no communication problems), and more often had a follow-up (not first)
      appointment. Other parameters were not significant (appointment day of week and
      time of day, gender, residency status, insurance coverage, family physician,
      medical consequences, covert addiction). CONCLUSIONS: The no-show rate was within
      the range for comparable settings. Several parameters associated with no-shows
      reflected specifics of a hospital-based adult outpatient clinic that mainly
      serves middle-to-low socio-economic classes and is a referral clinic for refugees
      in a middle-sized European city with a high percentage of foreigners with
      different backgrounds and languages. Planned interventions should consider local
      factors.

PMID- 17555783
TI  - Associations between mild-to-moderate anaemia in pregnancy and helminth, malaria
      and HIV infection in Entebbe, Uganda.
AB  - It is suggested that helminths, particularly hookworm and schistosomiasis, may be
      important causes of anaemia in pregnancy. We assessed the associations between
      mild-to-moderate anaemia (haemoglobin >8.0 g/dl and <11.2 g/dl) and helminths,
      malaria and HIV among 2507 otherwise healthy pregnant women at enrolment to a
      trial of deworming in pregnancy in Entebbe, Uganda. The prevalence of anaemia was
      39.7%. The prevalence of hookworm was 44.5%, Mansonella perstans 21.3%,
      Schistosoma mansoni 18.3%, Strongyloides 12.3%, Trichuris 9.1%, Ascaris 2.3%,
      asymptomatic Plasmodium falciparum parasitaemia 10.9% and HIV 11.9%. Anaemia
      showed little association with the presence of any helminth, but showed a strong
      association with malaria (adjusted odds ratio (AOR) 3.22, 95% CI 2.43-4.26) and
      HIV (AOR 2.46, 95% CI 1.90-3.19). There was a weak association between anaemia
      and increasing hookworm infection intensity. Thus, although highly prevalent,
      helminths showed little association with mild-to-moderate anaemia in this
      population, but HIV and malaria both showed a strong association. This result may
      relate to relatively good nutrition and low helminth infection intensity. These
      findings are pertinent to estimating the disease burden of helminths and other
      infections in pregnancy. [Clinical Trial No. ISRCTN32849447].

PMID- 17555784
TI  - The influence of active hexose correlated compound (AHCC) on cisplatin-evoked
      chemotherapeutic and side effects in tumor-bearing mice.
AB  - Cisplatin (cis-diaminedichloroplatinum (II) or CDDP) (a widely used platinum
      containing anticancer drug) is nephrotoxic and has a low percentage of tolerance
      in patients during chemotherapy. The active hexose correlated compound (AHCC) is
      an extract of Basidiomycotina marketed as a supplement for cancer patients due to
      its nutrients and fibre content and its ability to strengthen and optimize the
      capacity of the immune system. The possibility that AHCC could reduce the side
      effects of cisplatin was assessed in the tumor-bearing BALB/cA mice on the basis
      of the ability to ameliorate the cisplatin-induced body weight loss, anorexia,
      nephrotoxicity and hematopoietic toxicity. Although cisplatin (8 mg/kg body
      weight) reduced the size and weight of the solid tumors, supplementation with
      AHCC significantly enhanced cisplatin-induced antitumor effect in both the size
      (p<0.05) and weight (p<0.05). Food intake in the cisplatin-treated mice were
      decreased following commencement of treatment and this remained low compared with
      the cisplatin-untreated group (control) throughout the experiment period.
      Supplementation with AHCC increased the food intake in the cisplatin-treated
      mice. The blood urea nitrogen and serum creatinine concentrations, and the ratio
      of blood urea nitrogen to serum creatinine were significantly increased in the
      cisplatin alone treated group compared to the control group. Their increased
      levels were mitigated by supplementation with AHCC (100 mg/kg body weight) in the
      cisplatin-treated group. AHCC was also able to modulate the suppression of bone
      marrow due to cisplatin and the improvement was statistically significant. The
      histopathological examination of the kidney revealed the presence of cisplatin
      induced damage and this was modulated by AHCC treatment. The potential for AHCC
      to ameliorate the cisplatin-evoked toxicity as well as the chemotherapeutic
      effect could have beneficial economic implications for patients undergoing
      chemotherapy with cisplatin.

PMID- 17555785
TI  - The simian varicella virus genome contains an invertible 665 base pair terminal
      element that is absent in the varicella zoster virus genome.
AB  - Simian varicella virus (SVV) causes chickenpox in monkeys, establishes latency
      and reactivates to produce zoster thus providing a model to study human varicella
      zoster virus (VZV) infection. Sequence analysis of a recombinant cosmid clone
      containing the left end of the SVV genome revealed a 665 base pair (bp) segment
      that is absent in VZV DNA. This segment inverts and contains 507 bp of unique
      sequences flanked on either side by 79 bp inverted repeats, making the SVV genome
      to be 124,785 bp in size. Part of the inverted repeat sequence (64 bp) is also
      present at the junction of the long and short segments of the SVV genome. The
      terminal DNA sequences are conserved among different SVV isolates and present in
      tissues from infected monkeys. The terminal region is transcriptionally active
      and is also present in the genomes of other animal varicelloviruses but absent in
      the VZV genome.

PMID- 17555787
TI  - Differential roles of contrast polarity reveal two streams of second-order visual
      processing.
AB  - Humans can easily segregate texture regions based on differences in contrast,
      orientation, and contrast polarity. It has been suggested that these abilities
      can be inclusively modeled by 2nd-order visual mechanisms that detect changes in
      the half-wave rectified outputs of orientation-selective filters. Using a
      subthreshold-summation paradigm, however, we show that modulations of contrast
      polarity are detected by mechanisms that pool signals of different orientations
      while modulations of orientation are detected by mechanisms that pool signals of
      different contrast polarities. The results support the existence of two streams
      of 2nd-order processing, one that receives the full-wave rectified inputs from
      oriented filters, the other separate half-wave rectified outputs from on-center
      and off-center filters pooled across all orientations. The two-stream model is
      shown to predict the perceptual effects of changes to the skewness statistics of
      natural-image textures, and to solve a contradiction among previous data
      concerning the detection of contrast modulation.

PMID- 17555786
TI  - Microarray analysis of glial cells resistant to JCV infection suggests a
      correlation between viral infection and inflammatory cytokine gene expression.
AB  - The human polyomavirus, JCV, has a highly restricted tropism and primarily
      infects glial cells. The mechanisms restricting infection of cells by JCV are
      poorly understood. Previously we developed and described a glial cell line that
      was resistant to JCV infection with the aim of using these cells to identify
      factors that determine JCV tropism. Gene expression profiling of susceptible and
      resistant glial cells revealed a direct correlation between the expression of
      inflammatory cytokines and susceptibility to JCV infection. This correlation
      manifested at the level of viral gene transcription. Previous studies have
      suggested a link between an increase in cytokine gene expression in HIV patients
      and the development of PML and these data supports this hypothesis.

PMID- 17555788
TI  - Kinetic analysis of palladium(II) adsorption process on condensed-tannin gel
      based on redox reaction models.
AB  - We have developed a novel recovery system of palladium (Pd) from wastes such as
      spent catalysts or scraps, using tannin gel particles synthesized from condensed
      tannin molecules. The Pd(II) ionic species are reduced to metallic Pd(0) on the
      network of the tannin gel: a two-electron transfer from the tannin gel to Pd(II).
      The kinetic study of the electron transfer was performed with a multiple reaction
      model containing an intermediate step (formation of a ligand-substituted Pd(II)
      tannin inner sphere complex), resulting in a better fit with the experimental
      results than with the single reaction model (outer sphere redox reaction), which
      means that the inner sphere redox mechanism is an appropriate reaction model for
      the Pd(II) adsorption process. Because the intermediate is included in the
      adsorption amount, the adsorption process can be divided into two steps: fast
      adsorption by the ligand substitution at the initial stage and slow adsorption by
      the subsequent redox reaction after the ligand substitution reaches an
      equilibrium state, with different adsorption rates between the Pd(II) ionic
      species (PdCl(+)>PdCl(2)>PdCl(3)(-),PdCl(4)(2-)).

PMID- 17555789
TI  - Enhanced degradation of benzo[a]pyrene by Mycobacterium sp. in conjunction with
      green alga.
AB  - Previous work in this laboratory has confirmed that the bacteria Mycobacterium
      sp. strain RJGII.135 and Sphingomonas yanoikuyae strain B1 and the green alga
      Selanastrum capricornutum strain UTEX 1648 degrade benzo[a]pyrene (BaP) to
      various BaP intermediates. S. capricornutum was first grown with BaP for 4 days.
      The organic extract of this media was then introduced into separate cultures of
      strain RJGII.135 and strain B1; separate cultures were grown with BaP for
      comparison. Cultures grown with BaP and those grown with the algal/BaP extract
      showed similar mineralization patterns. The quantity of total metabolites formed
      was greater in bacterial cultures grown with the algal/BaP extract than those
      grown with BaP alone. For strain RJGII.135, only 27% of the original BaP remained
      in cultures grown with the algal/BaP extract; 59% remained in cultures grown with
      BaP. For strain B1, only 6% of the original BaP remained in cultures grown with
      the algal/BaP extract; 38% remained in cultures grown with BaP. These results
      indicate that strategies utilizing organisms together may be necessary in being
      able to degrade large, recalcitrant polycyclic aromatic hydrocarbons (PAHs) such
      as BaP.

PMID- 17555790
TI  - Influences of metals on kinetics of methyl tert-butyl ether biodegradation by
      Ochrobactrum cytisi.
AB  - The influence of zinc, manganese, and nickel on the degradation of MTBE (methyl
      tert-butyl ether), by an aerobic MTBE-degrading strain, Ochrobactrum cytisi, were
      investigated. The result showed that unlike previous findings, O. cytisi was able
      to degrade MTBE through direct metabolism when MTBE was present as the only
      carbon source. The degradation rate of MTBE was rapid, completed within 80 h.
      MTBE biodegradation by this strain was stimulated at low concentrations of Zn(2+)
      (1-5 mg l(-1)) and Mn(2+) (1-5 mg l(-1)) but inhibited at high concentrations of
      Zn(2+) (20 mg l(-1)) and Mn(2+) (20 mg l(-1)), and at low concentration of Ni(2+)
      (1-4 mg l(-1)). Kinetic parameters for MTBE degradation in the presence or
      absence of metals were obtained through nonlinear regression and a least-square
      minimization procedure. In all cases, a good agreement was achieved between
      kinetic simulations and experimental results.

PMID- 17555791
TI  - Predicting Pb bioavailability to freshwater microalgae in the presence of fulvic
      acid: algal cell density as a variable.
AB  - In order to better understand the relationship between lead speciation and its
      bioavailability in natural waters, the interactions between Pb(II), fulvic acid
      and the freshwater alga, Chlorella kesslerii were studied at various algal cell
      densities. An increase in cellular lead or fulvic acid adsorbed to algae was
      observed with decrease of the cell density from ca. 10(7) to 10(5)cells ml(-1).
      In the presence of fulvic acid, cellular Pb was greater than that expected for
      the same free lead ion concentrations in the absence of fulvic acid in agreement
      to our previous study. This effect was found to be more pronounced at lower cell
      density, in accordance with increased fulvic acid adsorption to algae. Good fit
      between experimental observations and model predictions of cellular Pb at various
      cell densities, was observed by assuming that fulvic acid adsorbed to algae give
      rise to additional binding sites for Pb(II). The findings of this study indicate
      that a further extension of the biotic ligand model which includes the formation
      of a ternary complex and cell density (or concentration) as an input parameter is
      needed to improve its site-specific predictive capacity, especially in the case
      of dissolved organic matter-rich surface waters. This extension of predictive
      capacity would allow to reduce the deviations from the BLM model predictions for
      microalgae in the presence of dissolved organic matter and hence will serve as a
      mechanistic tool for establishing ambient site-specific water quality criteria.

PMID- 17555792
TI  - Removal of Prussian blue from contaminated soil in the rhizosphere of cyanogenic
      plants.
AB  - The fate of radiolabeled cyanide in soil was investigated during exposure to
      cyanogenic plant species, sorghum (Sorghum bicolor var. P721) and flax (Linum
      usitassimum var. Omega-Gold), in fully-contained growth chambers. Labeled cyanide
      was subject to microbial transformation, assimilation by plant roots,
      incorporation and biodegradation in plant tissue. For this study, (14)C-labeled
      cyanide was added to soil, and distribution of (14)C activity was assessed before
      plant establishment and after harvest. After 3 months of plant growth, 7% of the
      (14)C-labeled cyanide was converted to (14)CO(2) with sorghum and 6% with flax,
      compared with only 2% conversion in unplanted soil. A small amount of unaltered
      cyanide was shown to be accumulated by the plants (approximately 140 mg
      cyanide/kg plant or <0.1% of the total). Results from this experiment demonstrate
      the potential of cyanogenic plants for use in phytoremediation of cyanide
      contaminated soil.

PMID- 17555793
TI  - Frozen-section diagnosis by wireless telepathology and ultra portable computer:
      use in pathology resident/faculty consultation.
AB  - Residents in anatomic pathology are allowed increased diagnostic responsibility
      including the initial interpretation of intraoperative frozen-section
      consultations during their years of training. This frozen-section responsibility
      requires staff faculty backup for diagnostic confirmation and consultation. In
      this study, we tested a telepathology system using an ultra portable computer
      with a 4.5-in diagonal screen (scrolled image size of 2.5 x 1.75 in, width x
      height) and both wireless Local Area Network (LAN) final connection from a DSL
      and wireless Wide Area Network (WAN) telecommunications. The diagnostic agreement
      for a chief resident/faculty staff duo using telepathology for 100 consecutive
      frozen-section cases (50 with wireless LAN final connection and 50 with wireless
      WAN) with limited clinical information was compared with the original frozen
      section diagnosis rendered by other staff pathologists. There was diagnostic
      agreement for 95 of the 100 cases. For the 5 that were discordant, 2 were deemed
      to be errors in the original frozen-section diagnosis; 1 was not clinically
      important; and 2 were believed to have potential clinical implications. For the 2
      having potential clinical importance, the absence of knowledge of the gross
      findings in each case and the preoperative biopsy results for one specimen
      contributed to the misinterpretation of the frozen sections. The median time
      between transmission of image(s) from the chief resident to the faculty
      consultant until diagnosis by the latter was 1 minute 42 seconds for wireless WAN
      and 51 seconds for the wireless LAN final connection to the display device. We
      conclude that a telepathology system using an ultra portable computer and
      wireless telecommunications is useful for frozen-section consultation between an
      experienced resident and a faculty member in pathology.

PMID- 17555794
TI  - The expression of vascular dendritic cells in human atherosclerotic carotid
      plaques.
AB  - Atherosclerosis is currently considered a chronic inflammatory disease, and
      evidence is accumulating for a role of the immune system in the progression of
      atherosclerosis. Dendritic cells are specialized antigen-presenting cells with
      the unique ability to initiate a primary immune response to certain antigens by
      the activation of naive T-lymphocytes. Although dendritic cells are well known to
      be important in the development of different diseases, studies of vascular
      dendritic cells in atherosclerosis are rare, and their role is not clearly
      understood. Therefore, we investigated the immunohistochemical expression of
      vascular dendritic cells in atherosclerotic plaques. Between April 2003 and
      December 2005, carotid endarterectomy was performed in 26 consecutive patients,
      and 27 carotid plaque specimens were analyzed. We investigated the
      immunohistochemical expression of vascular dendritic cells in human carotid
      plaques by measuring the signal intensity of fascin-positive cells using an image
      analyzer. In addition, these immunohistochemical results were related to clinical
      data. The highest signal intensity of dendritic cells was found in plaque
      shoulders, and the mean signal intensity of dendritic cells was significantly
      higher in complicated than in uncomplicated plaques (P = .0029). Moreover, the
      mean signal intensity of dendritic cells in plaques from symptomatic patients was
      significantly elevated compared with plaques from asymptomatic patients (P =
      .0004). Although atherosclerotic plaque instability is determined by multiple
      factors, the immune and inflammatory pathways play a particularly important role.
      Dendritic cells play a role in atherosclerosis, and the present study suggests
      that the expression of dendritic cells in human carotid arteries may be strongly
      associated with the occurrence of ischemic stroke.

PMID- 17555795
TI  - Expression of hypoxia-inducible factor 1alpha, hypoxia-inducible factor 2alpha,
      and von Hippel-Lindau protein in epithelial ovarian neoplasms and allelic loss of
      von Hippel-Lindau gene: nuclear expression of hypoxia-inducible factor 1alpha is
      an independent prognostic factor in ovarian carcinoma.
AB  - The hypoxia-inducible factor (HIF) is a transcriptional factor with important
      roles in tumor biology. To clarify the possible involvement of the HIF-alpha
      subunit and von Hippel-Lindau (VHL) protein in the development and progression of
      ovarian carcinoma, we analyzed the immunohistochemical expressions of HIF-1alpha,
      HIF-2alpha, and VHL in 107 cases of epithelial ovarian tumors. In addition, we
      examined loss of heterozygosity (LOH) at VHL gene loci. The frequency of the
      cytoplasmic expression of HIF-2alpha in carcinomas was higher than that in benign
      and borderline tumors (P < .0001). Furthermore, the nuclear expression of HIF
      1alpha and the cytoplasmic expression of HIF-2alpha were significantly higher in
      tumors of FIGO (International Federation of Gynecology and Obstetrics) stages III
      and IV than in those of stages I and II. On the other hand, the cytoplasmic
      expression of HIF-1alpha did not show differences among histological
      malignancies. There was a positive correlation between nuclear HIF-1alpha
      expression and vascular endothelial growth factor (rho = 0.320, P < .001).
      Although LOH at the VHL gene locus was frequent in ovarian carcinomas (24%),
      there is no significant correlation between LOH and loss of VHL expression. In 22
      clear cell carcinomas, VHL expression showed a significantly negative correlation
      with the nuclear expression of HIF-1alpha (rho = -0.529, P = .0153). The log-rank
      test showed that nuclear positive immunostaining for HIF-1alpha (P = .002) and
      cytoplasmic positive immunostaining for HIF-2alpha (P = .0112) in tumor cells are
      associated with poor prognosis of patients with ovarian carcinoma. Multivariate
      analysis also showed that the nuclear expression of HIF-1alpha is an independent
      prognostic factor. These results show that the HIF-alpha subunit represents an
      important biomarker in the evaluation of the prognosis of patients with ovarian
      carcinoma.

PMID- 17555796
TI  - Glutathione S-transferase: differential expression of alpha, mu, and pi
      isoenzymes in benign prostate, prostatic intraepithelial neoplasia, and prostatic
      adenocarcinoma.
AB  - Glutathione S-transferases (GST) comprise a family of enzymes which are critical
      for inactivation of toxins and carcinogens. We examined the cellular expression
      of multiple subclasses of GST immunohistochemically in 25 radical prostatectomy
      specimens with clinically localized prostate cancer. Gleason scores ranged from 5
      to 9, and pathologic stages varied from pT2a to pT3b (all N0M0). Antibodies were
      directed against GST Ya, Yc, and Yk (alpha subclass), Yb1 (micro subclass), and
      YPr (pi subclass). The percentage of positive cells and intensity of staining was
      assessed for benign epithelium, high-grade prostatic intraepithelial neoplasia
      (PIN), and adenocarcinoma. GSTalpha (Ya) was detected in 30% of cells (mean) in
      benign acini, 4.9% of cells in high-grade PIN, and 4.5% of cells in
      adenocarcinoma. The corresponding results for alpha (Yk), micro (Yb1), and pi
      (Yp) were 12.7%, 10.9%, and 3.5%; 8.7%, 5.2%, and 0.6%; and 66.7,% 0%, and 0%,
      respectively. GST Yc (alpha subclass) displayed the lowest level of expression,
      with diffuse weak staining in scattered benign secretory cells and only single
      cells (<1%) in high-grade PIN and carcinoma. These results demonstrate consistent
      reduction or loss of expression of all subclasses of GST with progression of
      prostatic neoplasia from benign epithelium to high-grade PIN and carcinoma. We
      hypothesize that carcinogenesis in the prostate results from impaired cellular
      handling of mutagenic agents owing to reduction or loss of expression of multiple
      GST and other detoxifying and antimutagenesis agents.

PMID- 17555797
TI  - Evaluation of HER-2 gene status in gastric carcinoma using immunohistochemistry,
      fluorescence in situ hybridization, and real-time quantitative polymerase chain
      reaction.
AB  - HER-2 gene amplification and the overexpression of HER-2 protein have been
      observed in various solid tumors, including gastric carcinomas. HER-2 gene
      amplification has attracted research attention since the development of the new
      therapeutic agent trastuzumab. Here, we evaluated HER-2 status in the surgically
      resected tissues of 248 gastric carcinoma cases using immunohistochemistry (IHC),
      fluorescence in situ hybridization (FISH), and real-time quantitative polymerase
      chain reaction (q-PCR) and compared the results. In addition, we compared
      clinicopathologic characteristics with the presence of HER-2 gene amplification
      and with protein overexpression. Among the 248 cases, 56 (22.6%) cases showed HER
      2 overexpression (2+ or 3+) by IHC and 19 cases (7.7%) showed HER-2 gene
      amplification by FISH. Four (2.1%) of the 192 cases negative (0 or 1+) by IHC
      showed amplification by FISH, whereas 15 (26.8%) of the 56 cases with HER-2
      protein overexpression showed HER-2 amplification by FISH. The correlation
      between IHC and FISH results was statistically significant (P < .001). HER-2
      protein overexpression and HER-2 gene amplification were common in cases with a
      well- or moderately differentiated histology according to the World Health
      Organization classification (P < .001) and in cases of intestinal type by the
      Lauren classification (P < .001). Real-time q-PCR results showed that calculated
      HER-2/GAPDH ratios were higher in amplified cases with 100.0% sensitivity and
      96.9% specificity using FISH results as the standard. Measurements of HER-2
      expression by FISH and real-time q-PCR and of HER-2 protein by IHC were found to
      be highly concordant at determining HER-2 status in gastric carcinoma.

PMID- 17555798
TI  - Comment on the article 'Radionuclide dating (Pb-210, Cs-137, Am-241) of recent
      lake sediments in a highly active geodynamic setting (Lakes Puyehue and Icalma
      Chilean Lake District)'.
AB  - The correlation of Cs-137 specific activity profiles with the historical fallout
      sequence in the study region is essential in sediment cores dating using this
      technique. The authors of the referenced article considered 1965 the end of Cs
      137 fallout in the study region, omitting the South Pacific nuclear test from
      1966 to 1974, proved that generated the most intense Cs-137 fallout.

PMID- 17555799
TI  - Estimating uncertainty in terrestrial critical loads and their exceedances at
      four sites in the UK.
AB  - Critical loads are the basis for policies controlling emissions of acidic
      substances in Europe and elsewhere. They are assessed by several elaborate and
      ingenious models, each of which requires many parameters, and have to be applied
      on a spatially-distributed basis. Often the values of the input parameters are
      poorly known, calling into question the validity of the calculated critical
      loads. This paper attempts to quantify the uncertainty in the critical loads due
      to this "parameter uncertainty", using examples from the UK. Models used for
      calculating critical loads for deposition of acidity and nitrogen in forest and
      heathland ecosystems were tested at four contrasting sites. Uncertainty was
      assessed by Monte Carlo methods. Each input parameter or variable was assigned a
      value, range and distribution in an objective a fashion as possible. Each model
      was run 5000 times at each site using parameters sampled from these input
      distributions. Output distributions of various critical load parameters were
      calculated. The results were surprising. Confidence limits of the calculated
      critical loads were typically considerably narrower than those of most of the
      input parameters. This may be due to a "compensation of errors" mechanism. The
      range of possible critical load values at a given site is however rather wide,
      and the tails of the distributions are typically long. The deposition reductions
      required for a high level of confidence that the critical load is not exceeded
      are thus likely to be large. The implication for pollutant regulation is that
      requiring a high probability of non-exceedance is likely to carry high costs. The
      relative contribution of the input variables to critical load uncertainty varied
      from site to site: any input variable could be important, and thus it was not
      possible to identify variables as likely targets for research into narrowing
      uncertainties. Sites where a number of good measurements of input parameters were
      available had lower uncertainties, so use of in situ measurement could be a
      valuable way of reducing critical load uncertainty at particularly valuable or
      disputed sites. From a restricted number of samples, uncertainties in heathland
      critical loads appear comparable to those of coniferous forest, and nutrient
      nitrogen critical loads to those of acidity. It was important to include
      correlations between input variables in the Monte Carlo analysis, but choice of
      statistical distribution type was of lesser importance. Overall, the analysis
      provided objective support for the continued use of critical loads in policy
      development.

PMID- 17555800
TI  - Effects of pesticides on community structure and ecosystem functions in
      agricultural streams of three biogeographical regions in Europe.
AB  - There is a paucity of large-scale field investigations on the effects of organic
      toxicants on stream macroinvertebrate community structure and ecosystem
      functions. We investigated a total of 29 streams in two study areas of France and
      Finland for pesticide exposure, invertebrates and leaf-litter breakdown. To link
      pesticide exposure and community composition we applied the trait-based Species
      At Risk (SPEAR) indicator system. In the French region, pesticide stress was
      associated with a decrease in the relative abundance and number of sensitive
      species in the communities. The presence of undisturbed upstream reaches partly
      compensated the effects of pesticide contamination. Functional effects of
      pesticides were identified by a 2.5-fold reduction of the leaf-litter breakdown
      rate that was closely correlated with the structural changes in the contaminated
      streams. No effects of pesticides were observed in Finnish streams since
      contamination with pesticides was very low. In a follow-up analysis, the SPEAR
      approach successfully discriminated between reference and contaminated sites
      across different biogeographical regions, also including results of a previous
      field study in North Germany. Furthermore, change of the community structure was
      detectable at a concentration range as low as 1/100 to 1/1000 the acute 48 h-LC50
      of Daphnia magna. Our findings demonstrate that pesticides may influence the
      structure and function of lotic ecosystems and that the SPEAR approach can be
      used as a powerful tool in biomonitoring over large spatial scales.

PMID- 17555801
TI  - Exposure assessment of a burning ground for chemical ammunition on the Great War
      battlefields of Verdun.
AB  - The destruction of arsenical shells from the 1914/18 war in the vicinity of
      Verdun (France) during the 1920s resulted in a locally limited but severe soil
      contamination by arsenic and heavy metals. At the study site, the main part of
      the contaminant inventory occurs in the upper 20 cm of the topsoil which is
      essentially composed of combustion residues. Besides, some Cu (cmax.=16,877
      mg/kg) and Pb (cmax.=26,398 mg/kg) in this layer, As (cmax.=175,907 mg/kg) and Zn
      (cmax.=133,237 mg/kg) were detected in very high concentrations. The mobilities
      of Cu, Mn, Pb and Zn in the soil system were derived from ammonium nitrate
      eluates. They are strongly influenced by the soil pH and can be described by
      quadratic regression curves from which threshold pH values were calculated. Below
      these values more than 10% of the element content was available as mobile
      species. Within the examined pH range, this method could not be adopted for
      arsenic, because the mobility of As was only slightly controlled by the soil pH.
      In the heavily contaminated topsoil, Cu and Pb were fixed by the moderately
      acidic soil pH which varied from 4.8 to 5.8. No migration to the underlying
      horizons occurred. A different behavior was observed for As and Zn. The
      calculated threshold pH of Zn was 5.5, so certain amount of this element was
      transferred to the subsoil and the leachate (cmax.=350 microg/l). However, a
      major dispersion of Zn was prevented by a rise of the soil pH in the carbonate
      containing subsoil. Elevated concentrations of As were found in all soil horizons
      up to a depth of 2 m and also in the leachate (cmax.=2377 microg/l). Contrary to
      Cu, Pb and Zn the mobility of As evidently was less affected by the subsoil.
      Regarding organic contaminants, nitroaromatic explosives were detected only in
      minor concentrations in the soil (cmax.=14.7 mg/kg) and the leachate (cmax.=13.5
      microg/l). No aromatic organoarsenicals were detected in the soil and the
      leachate samples. The main hazard of the site is the severe arsenic contamination
      and the transfer of this carcinogen by leachate, surface runoff and probably by
      wind. Nevertheless, some studies on the effects of the contaminant inventory on
      the local vegetation revealed that ammonium nitrate elutable zinc is responsible
      for the spatial distribution of some tolerant plant species and not arsenic.
      Previously undetected buried munitions from the former delaboration facility can
      be an other source of environmental contaminants. This is supported by elevated
      concentrations of chlorate (cmax.=71 mg/l) and perchlorate (cmax.=0.8 mg/l)
      detected in the leachate samples. This is the second report about environmental
      contamination related to post-war ammunition destruction activities along the
      1914/18 Western Front.

PMID- 17555803
TI  - A factor X-TFPI hybrid protein inhibits B16 melanoma metastatic growth in mice.

PMID- 17555802
TI  - CD39/NTPDase-1 activity and expression in normal leukocytes.
AB  - INTRODUCTION: CD39/NTPDase-1 is a cell surface enzyme expressed on leukocytes and
      endothelial cells that metabolizes ATP to ADP and AMP. CD39 is expressed on
      numerous different types of normal leukocytes, but details of its expression have
      not been determined previously. METHODS: We examined CD39 expression and activity
      in leukocytes isolated from healthy volunteers. Expression of CD39 on leukocytes
      was measured by FACS and activity of CD39 in lymphocytes and neutrophils was
      determined by an enzymatic radio-TLC assay. RESULTS: We established that CD39 is
      expressed on neutrophils, lymphocytes, and monocytes. The enzyme is found on >90%
      of monocytes, neutrophils, and B-lymphocytes, and 6% of T-lymphocytes and natural
      killer cells. Per cell density of expression varied, with the highest expression
      on monocytes and B-lymphocytes. ATPase and ADPase activities were highest on B
      lymphocytes, lower on neutrophils, lowest on T-lymphocytes. The ratio of
      ADPase:ATPase activity was 1.8 for neutrophils and B-lymphocytes and 1.4 for T
      lymphocytes. Hypertensive volunteers had lower levels of CD39 on their T
      lymphocytes and NK cells. No correlation between age, gender, ethnic background,
      or cholesterol level and CD39 expression was observed. CONCLUSIONS: We conclude
      that CD39 activity and expression are present to varying degrees on all
      leukocytes types examined. Differences between leukocyte types should be
      considered when examining CD39 in disease states.

PMID- 17555804
TI  - Identification of platelet hyper-reactivity measured with a portable device
      immediately after percutaneous coronary intervention predicts in stent
      thrombosis.
AB  - INTRODUCTION: Platelet hyper-reactivity, despite a standard anti-thrombotic
      therapy, is a recognized risk factor for recurrent myocardial ischemia and in
      stent thrombosis following PCI. We have investigated whether this detrimental
      condition, measured by collagen-epinephrine closure times (CEPI-CT) with the
      Platelet Function Analyzer (PFA-100) device could predict IST defined as the
      composite of cardiovascular death or myocardial infarction. MATERIALS AND
      METHODS: CEPI-CT was measured in 256 consecutive patients with stable angina
      (n=103) or ACS (n=153) 30+/-8 h after PCI (T 0) and 1 month later (T1). All
      patients were followed up for a mean period of 9 months. Platelet hyperactivity
      was defined as a CEPI-CT<190 s. RESULTS: Baseline CEPI-CT<190 s was associated
      with a higher rate of death or MI (LogRank chi2=4.23, p=0.039) as compared with
      CEPI-CT>190 s (4.6% vs. 0.7%). Multivariable analysis after adjustment for other
      risk factors confirmed that baseline CEPI-CT<190 s was an independent correlate
      for death or MI (Hazard ratio 6.981, p=0.008). At T1 there was a significant
      prolongation of CEPI-CT (p=0.03) from 208+/-64 s to 240+/-59 s but T1 did not
      predict any event. CONCLUSIONS: A CEPI-CT<190 s measured within the first 24 h
      following PCI predicts IST defined as the occurrence of death or MI.

PMID- 17555805
TI  - Platelet aggregation abnormalities in patients with recurrent fetal losses.
AB  - INTRODUCTION: There are some studies reporting that platelets might have a role
      in cases with recurrent fetal losses. The aim of this study is to evaluate the
      importance of platelet aggregation abnormalities in this patient group. MATERIALS
      AND METHODS: In this study, platelet aggregation abnormalities were compared in
      56 cases with recurrent fetal losses (29 of these 56 patients have >or=3 losses)
      and in 33 healthy female controls with no previous history of fetal loss.
      Platelet aggregation studies were performed with optical turbidometric method by
      using ADP (5 microM), collagen (0.2 mg/ml) and epinephrine (10 microM). RESULTS:
      We did not find any statistically significant difference between patient (56
      cases with >or=2 fetal losses and 29 of them with >or=3 fetal losses) and control
      groups for platelet aggregation abnormalities. CONCLUSIONS: The data we have
      obtained suggest that severe platelet aggregation abnormalities are not the rule
      in patients with recurrent fetal losses.

PMID- 17555806
TI  - Repeat organic dust exposure-induced monocyte inflammation is associated with
      protein kinase C activity.
AB  - BACKGROUND: Organic dust exposure results in an inflammatory response that
      attenuates over time, but repetitive exposures can result in chronic respiratory
      diseases. Mechanisms underlying this modulated response are not clear. OBJECTIVE:
      This study investigated the effects of repeat versus single organic dust exposure
      induced inflammatory mediators and protein kinase C (PKC) activity in monocytes.
      METHODS: Settled organic dust was obtained from swine confinement facilities.
      Promonocytic THP-1 cells and human peripheral blood monocytes were pretreated
      with or without dust extract and then restimulated. Culture supernatants were
      evaluated for TNF-alpha, IL-6, CXCL8, and IL-10. Responses were compared with
      endotoxin-depleted dust, LPS, and peptidoglycan. PKC isoform (alpha, delta,
      epsilon, zeta) activation was evaluated by direct kinase activity. PKC isoform
      inhibitors' effects on TNF-alpha secretion were studied. RESULTS: Single exposure
      to organic dust stimulated monocyte secretion of TNF-alpha, IL-6, CXCL8, and IL
      10 compared with unstimulated cells. TNF-alpha and IL-6 were diminished in
      pretreated cells restimulated with dust. Secretion of CXCL8 and IL-10 remained
      persistently elevated. TNF-alpha responses were retained after marked depletion
      of endotoxin. Dust exposure induced significant PKC alpha, delta, epsilon, and
      zeta activation, peaking at 30 to 60 minutes. PKC isoform activation was
      attenuated in repeat exposed cells. Inhibition of PKCalpha and PKCepsilon reduced
      dust-induced TNF-alpha secretion. CONCLUSION: Repeat organic dust exposure
      modulated inflammatory mediator production in monocytes independent of endotoxin.
      The inability of PKC to be reactivated may account for this observation. CLINICAL
      IMPLICATIONS: Targeting PKC and specific mediators associated with repetitive
      organic dust exposure may result in novel therapeutic strategies.

PMID- 17555807
TI  - Cervical diameter in relation to uterine and cervical EMG activity in early
      postpartum dairy cows with retained placentas after PGF2alpha induced calving.
AB  - The cervix must regain its normal diameter after parturition. Until now, little
      has been known about the pattern of cervical closure and the possible influences
      of myometrial and cervical contractions in this process. We continuously measured
      the cervical diameter with ultrasound cervimetry during the first 48h after
      calving in six cows with retained fetal membranes, while uterine (n=6) and
      cervical outer muscular layer (n=4) electromyographic (EMG) activity was measured
      with bipolar EMG electrodes. We found that the cervical diameter which was 6.2cm
      (+/-0.7) at 1.4h after calving, initially increased to 9.0cm (+/-1.0) during the
      first 14.8h (+/-2.8) postpartum. After this time, the diameter decreased
      gradually to 5.3cm (+/-1.0) at 48h after calving. The overall EMG activity after
      parturition decreased by 59% (+/-6) and 35% (+/-17) for the uterus and cervix,
      respectively. The decrease in EMG activity was due to a 50% (+/-7) decrease in
      EMG amplitudes of the myometrium; the EMG amplitudes of the cervix decreased by
      only 8% (+/-21) (P>0.05). At the same time in the cervix, burst frequency
      decreased by 69% (+/-17), while the decrease in burst frequency of the myometrium
      was only 11% (+/-5) (P>0.05). Uterine myometrial and cervical EMG activity after
      parturition showed burst patterns. These contractions of the uterus and cervix
      were accompanied by and correlated with transient dilatations of the caudal
      cervix. This could have functional relevance in the evacuation of the uterus.

PMID- 17555808
TI  - Differences in boar sperm head shape and dimensions recorded by computer-assisted
      sperm morphometry are not related to chromatin integrity.
AB  - Although sperm head shape and relative dimensions are considered reliable
      indicators of sperm quality, their quantification is most often operator-driven,
      e.g., subjective. Artificial insemination semen doses from 35 mature stud boars
      of known fertility and belonging to three breeds and two hybrid breeds (Duroc,
      Large White, Landrace, respectively, Yorker and Risco) were used in this study.
      Sperm samples were extended to 100x10(6) cells per mL and 10microL of the sperm
      suspension used to made smears which, stained, were examined using phase contrast
      microscopy interfaced with an automated sperm morphology analyzer (ASMA, ISAS).
      Each sperm head was measured for four primary parameters [area (A) microm(2),
      perimeter (P) mum, length (L) microm, width (W) microm], and four derived
      parameters of head shape [(L/W), (4piA/P(2)), ((L-W)/(L+W)), (piLW/4A)].
      Definition of head size was statistically performed. The threshold for each class
      was established on the basis of the area values, considering the 25th percentile
      as small and the 75th percentile as large spermatozoa. In a second step, sperm
      head shape was determined as normal, elliptic, abnormal (rugose) contour, long or
      irregular and percentiles set as above to define spermatozoa with normal values
      for each shape parameter. Significant differences were found among breeds in the
      size of morphologically normal spermatozoa, which were significantly larger and
      more elliptic (P<0.001) in the Duroc breed. Sperm chromatin integrity was studied
      using the SCSA-assay, with significant differences observed in the degree of
      fragmentation intensity (DFI) although this value was consistently low in all
      animals studied. The hereby-validated ASMA was able to determine significant
      differences in sperm shape and dimensions among breeds, which were not
      accompanied by deviations in chromatin structure neither within nor between
      fertile AI-boars.

PMID- 17555809
TI  - Development of OPS vitrified pig blastocysts: effects of size of the collected
      blastocysts, cryoprotectant concentration used for vitrification and number of
      blastocysts transferred.
AB  - Unhatched blastocysts from Large White hyperprolific gilts (n=103) were
      identified, measured and vitrified using the Open Pulled Straw (OPS) technique to
      evaluate the effects of the collected blastocyst size and cryoprotectant
      concentrations used for vitrification, and the number of embryos transferred per
      recipient. Vitrified/warmed blastocyst viability was estimated in vitro, as the
      percentage of embryos developing after 72h, and in vivo, on pregnancy Day 30. In
      the in vitro study, we compared the use of three cryoprotectant concentrations
      (16.5, 18, or 20% DMSO+16.5, 18, or 20% EG+0.4M sucrose). Survival rates differed
      significantly between the control (98.3%) and the three cryoprotectant
      concentrations (67, 62.3, and 57%, respectively). Blastocyst size at
      vitrification determined the further in vitro development of embryos (26%
      survival for blastocysts 126-144microm versus 100% for blastocysts >199microm).
      For the in vivo study, blastocysts were vitrified using cryoprotectant
      concentrations of 16.5 or 18% DMSO+EG and transferred surgically in groups of 20
      or 30 per recipient (n=40). Recipients were slaughtered on pregnancy D30. No
      significant differences were detected in gestation rates (50-70%) and embryo
      survival rates (14.7-25%), although survival was higher (P=0.0003) when 20
      blastocysts were transferred compared to 30 (24.7% versus 15.5%). Our findings
      indicate that best results, in terms of subsequent in vivo embryo survival, were
      achieved after transferring 20 embryos at the blastocyst or expanded blastocyst
      stage, previously vitrified using cryoprotectant concentrations of 16.5 or 18%.

PMID- 17555810
TI  - Immobilization of tyrosinase and alcohol oxidase in conducting copolymers of
      thiophene functionalized poly(vinyl alcohol) with pyrrole.
AB  - Immobilization of tyrosinase and alcohol oxidase is achieved in the copolymer of
      pyrrole with vinyl alcohol with thiophene side groups (PVATh-co-PPy) which is a
      newly synthesized conducting polymer. PVATh-co-PPy/alcohol oxidase and PVATh-co
      PPy/tyrosinase electrodes are constructed by the entrapment of enzyme in
      conducting copolymer matrix during electrochemical copolymerization. For
      tyrosinase and alcohol oxidase enzymes, catechol and ethanol are used as the
      substrates, respectively. Kinetic parameters: maximum reaction rates (V(max)) and
      Michaelis-Menten constants (K(m)) are obtained. V(max) and K(m) are found as 2.75
      micromol/(minelectrode) and 18 mM, respectively, for PVATh-co-PPy/alcohol oxidase
      electrode and as 0.0091micromol/(minelectrode) and 40 mM, respectively, for PVATh
      co-PPy/tyrosinase electrode. Maximum temperature and pH values are investigated
      and found that both electrodes have a wide working range with respect to both
      temperature and pH. Operational and storage stabilities show that although they
      have limited storage stabilities, the enzyme electrodes are useful with respect
      to operational stabilities.

PMID- 17555811
TI  - Differential expression of cathepsins and cystatin C in ovine uteroplacental
      tissues.
AB  - Cathepsins (CTSs) are peptidases that have biological roles in degrading
      extracellular matrix, catabolism of intracellular proteins, and processing of pro
      hormones. Cystatin C (CST3) is a secreted inhibitor of lysosomal cysteine
      proteases cathepsin B (CTSB) and CTSL. Our working hypothesis is that cathepsins
      and cystatins play important roles in implantation and placentation in sheep.
      Expression of CTSB, CTSD, CTSH, CTSK, CTSL, CTSS, CTSZ, and CST3 mRNAs was
      detected in ovine uteroplacental tissues with distinct temporal and/or spatial
      expression patterns between Days 40 and 120 of pregnancy. Of particular note,
      CTSB, CTSD, and CTSZ mRNAs were predominantly detected in the chorion of the
      placenta and were more abundant in the placentomes than the intercaruncular
      endometria. CTSL and CST3 mRNAs were abundant in the endometrial epithelia and
      chorion, whereas CTSK, CTSS and CTSH mRNAs were most abundant in the stratum
      compactum stroma of the intercaruncular endometrium. Consistent with localisation
      of mRNAs, immunoreactive CTSL and CST3 proteins were mainly observed in the
      intercaruncular endometrial glands and intercotyledonary placenta during later
      pregnancy. These results support the working hypothesis that CTS and CST3 in
      uteroplacental tissues are involved in endometrial remodelling and placentation
      in sheep.

PMID- 17555812
TI  - Vasopressin-induced morphological changes in polarized rat hepatocyte multiplets:
      dual calcium-dependent effects.
AB  - Calcium-mobilizing hormones and neurotransmitters are known to affect cell
      morphology and function including cell differentiation or division. In this
      study, we examined vasopressin (AVP)-induced morphological changes in a polarized
      system of rat hepatocytes. Light and electron microscope observations showed that
      AVP induced microvilli formation and a remodeling of the isolated hepatocyte F
      actin submembrane cytoskeleton, these two events being correlated. We showed that
      these effects were rapid, reversible, observed at nanomolar AVP concentration and
      mediated by the V(1a) receptor. On polarized multicellular systems of
      hepatocytes, we observed a rapid reduction of the bile canaliculi lumen at the
      apical pole and micovilli formation at the basolateral domain with an enlarged F
      actin cytoskeleton. Neither activation of protein kinase C nor A via phorbol
      ester or dibutyryl cAMP induced such rapid morphological changes, at variance
      with ionomycin, suggesting that AVP-induced intracellular calcium rise plays a
      crucial role in those effects. By using spectrofluorimetry and cytochemistry, we
      showed that calcium release from intracellular stores was involved in bile
      canaliculus contraction, while calcium entry from the extracellular space
      controlled microvilli formation. Taken together, AVP and calcium-mobilizing
      agonists differentially regulate physiological hepatocyte plasma membrane events
      at the basal and the apical domains via topographically specialized calcium
      dependent mechanisms.

PMID- 17555813
TI  - The 8p11 myeloproliferative syndrome in a 3-year-old child.

PMID- 17555814
TI  - Matrilin-like molecules produced by circulating hemocytes of the zebra mussel
      (Dreissena polymorpha) upon stimulation.
AB  - Since invading the Great Lakes basin, USA, in 1980s, the zebra mussel (Dreissena
      polymorpha) has caused significant economic and ecologic devastation. The absence
      of major diseases led to the belief that zebra mussel may have extraordinary host
      defense mechanisms. This study was undertaken in order to better understand zebra
      mussel hemocyte functions. A suppressive subtraction hybridization (SSH) cDNA
      library was constructed from naive and stimulated hemocytes. Stimulation was
      performed using a mixture of lipopolysacchride (LPS), peptidoglycan (PGN), and
      zymosan (ZYM). In the stimulated hemocyte SHH cDNA library, 55 assembled ESTs
      were differentially expressed. These ESTs contained two putative immune- related
      molecules, namely, matrilin and agglutinin, three house-keeping genes, six cell
      metabolism/development genes, and 44 ESTs without putative functions. One of the
      putative adhesive molecules (CN-29, accession number: AM503947) was predicted to
      have homology with matrilins including the Von Willebrand Factor A (VWA) domain,
      which was identical to a matrilin molecule recently reported from the freshwater
      snail, Biomphalaria glabrata. Preliminary evidence suggests that the zebra mussel
      matrilin-like molecule is inducible upon hemocyte stimulation.

PMID- 17555815
TI  - Assessing risk of heavy metals from consuming food grown on sewage irrigated
      soils and food chain transfer.
AB  - Heavy metal pollution of soils resulting from sewage and wastewater irrigation is
      causing major concern due to the potential risk involved. In the present study
      Musi River and its environs were assessed for heavy metal contamination. The
      study area was assessed for Zn, Cr, Cu, Ni, Co and Pb in soils, forage grass,
      milk from cattle, leafy and non-leafy vegetables. Partitioning pattern of soil
      revealed high levels of Zn, Cr, and Cu associated with labile fractions, making
      them more mobile and plant available. The associated risk was assessed using
      hazard quotient (HQ). Human risk was assessed in people known to consume these
      contaminated foods by analyzing metals concentrations in venous blood and urine.
      Results showed high amounts of Pb, Zn, Cr, and Ni compared to permissible limits.
      HQ was found to be high for Zn followed by Cr and Pb with special reference to
      leafy vegetables particularly spinach and amaranthus.

PMID- 17555816
TI  - Does early intervention in infants at high risk for a developmental motor
      disorder improve motor and cognitive development?
AB  - Infants at high risk for developmental motor disorders are in general referred to
      early intervention (EI) services. It is a matter of debate to which extent EI may
      facilitate outcome in various developmental domains. We reviewed the effects of
      EI programmes aiming at promoting motor and cognitive development. With respect
      to motor development the data indicated that EI prior to term age probably is
      most effective when it aims at mimicking the intrauterine environment; after term
      age general developmental programmes probably are most effective. Some evidence
      was provided that EI prior to term age has a beneficial effect on cognitive
      development regardless the type of intervention which is applied. After term age
      only general developmental programmes seemed to have an effect on cognitive
      development. The review concludes with preliminary data on the effect a new
      intervention programme, COPCA, applied between 3 and 6 months corrected age on
      developmental outcome till 18 months. The results indicated that COPCA was more
      beneficial for the development of sitting behaviour and cognition than
      traditional paediatric physiotherapy.

PMID- 17555817
TI  - Kindling and sensitization as models for affective episode recurrence, cyclicity,
      and tolerance phenomena.
AB  - We use the non-homologous model of sensitization and kindling to help
      conceptualize processes occurring in the longitudinal course of bipolar disorder.
      The models help focus on the phenomena of episode recurrence, regression, and
      cycle acceleration occurring without medication and during treatment, when these
      progressive processes can re-emerge during tolerance development. The preclinical
      data suggest that it is the ratio of pathological versus adaptive factors
      mediated by changes in gene expression that mediate episode recurrence or
      suppression. During tolerance development, there may be selective loss of some
      episode-induced adaptive factors that may be re-engendered during a period off
      that medication. The models reveal long-term molecular changes induced by
      recurrent stresses, episodes of illness, and substances of abuse that can
      accumulate and lead to progressive increases in vulnerability to episode
      recurrence. The clinical and preclinical data converge in emphasizing the
      importance of prevention and early and sustained prophylaxis. New data also
      implicate brain-derived neurotrophic factor (BDNF) in genetic and environmental
      illness vulnerability and progression, as well as in the mechanisms of action of
      the mood stabilizers and antidepressants. Therapeutic agents may thus not only
      prevent recurrent affective episodes and their adverse consequences on the brain,
      behavior, and quality of life, but they may also be able to ameliorate the
      effects of stressors, and reverse or prevent some of the basic pathological brain
      mechanisms underlying illness progression.

PMID- 17555818
TI  - IL-17 attenuates the anti-apoptotic effects of GM-CSF in human neutrophils.
AB  - Interleukin (IL)-17A is a pleiotropic, pro-inflammatory cytokine that is
      implicated in chronic inflammatory and degenerative disorders. IL-17 has been
      demonstrated to link activated T-lymphocyte with the recruitment of neutrophils
      at sites of inflammation, however whether IL-17 can mediate neutrophil survival
      and subsequently affect inflammatory responses has not fully been elucidated. In
      our study, we demonstrate that human peripheral blood and HL-60 differentiated
      neutrophils express mRNA and cell surface IL-17A receptor. IL-17A does not affect
      the rate of spontaneous neutrophil apoptosis, however significantly decreased
      granulocyte macrophage-colony stimulating factor (GM-CSF)-mediated survival by
      antagonizing the signal transduction pathways of p38, Erk1/2 and signal
      transducer and activator of transcription (STAT) 5B. These events were associated
      with reduced myeloid cell lymphoma-1 (Mcl-1) protein levels, increased
      translocation and aggregation of Bax to mitochondria, decreased mitochondrial
      transmembrane potential and in an increase in caspase-3/7 activity. These events
      were independent of increased Fas or soluble Fas ligand expression levels. Taken
      together, our findings suggest that IL-17 may regulate neutrophil homeostasis and
      favor the resolution of inflamed tissues by attenuating the delay in neutrophil
      apoptosis induced by inflammatory cytokines.

PMID- 17555820
TI  - Functional assessment of two different accommodative intraocular lenses compared
      with a monofocal intraocular lens.
AB  - PURPOSE: To evaluate selected functional and physical properties of 2 models of
      accommodative intraocular lenses (IOLs) compared with those of a standard
      monofocal IOL. DESIGN: Prospective randomized comparative trial. PARTICIPANTS:
      Subjects were divided into 3 groups. In group 1, 30 eyes (19 subjects) received
      1CU IOL implantation; in group 2, 29 eyes (19 subjects) received AT-45 IOL
      implantation; and in group 3, 21 eyes (21 subjects) were implanted with a
      monofocal IOL as a control. INTERVENTION: Cataract surgery with implantation of
      the 1CU and AT-45 accommodative IOL models in the study groups, and the ACR6D
      monofocal IOL in the control group. MAIN OUTCOME MEASURES: Far and near distance
      visual parameters were assessed at 1, 6, and 12 months after surgery in the
      accommodative IOL groups, and at 1 and 12 months in the control group. Anterior
      segment anatomy was investigated by ultrasound biomicroscopy, with and without
      visual accommodative stimulation. RESULTS: The accommodative IOL groups
      significantly differed from the controls in terms of lower near-distance
      refractive addition (NDRA) and better distance-corrected near visual acuity
      (DCNVA), with P<0.001 at 1 year. The anterior IOL displacement during
      accommodation (DeltaACD) was significantly larger in the study groups, and this
      correlated with DCNVA. Until 6 months, the DeltaACD correlated with the solicited
      sclerociliary process rotation only in the study groups. CONCLUSION: This 12
      month study demonstrated that the accommodating IOLs achieved better clinical
      results than the monofocal IOL in terms of DCNVA and NDRA. These results support
      the hypothesis that accommodative IOLs proportionally react to ciliary body
      rotation, although this relationship became less evident at 12 months.

PMID- 17555819
TI  - Human homologues of a Borrelia T cell epitope associated with antibiotic
      refractory Lyme arthritis.
AB  - Antibiotic-refractory Lyme arthritis, which may result from infection-induced
      autoimmunity, is associated with HLA-DR molecules that bind an epitope of
      Borrelia burgdorferi (Bb) outer-surface protein A (OspA(165-173)) and with T cell
      reactivity with this epitope. One potential mechanism to explain these
      associations is molecular mimicry between OspA(165-173) and a self-peptide. Here,
      we searched the published human genome for peptides with sequence homology with
      OspA(165-173). The two peptides identified with the greatest sequence homology
      with the OspA epitope were MAWD-BP(276-288), which had identity at eight of the
      nine core amino acid residues, and T-span7(58-70), which had identity at six
      residues. MAWD-BP mRNA was expressed by synoviocytes, while T-span7 mRNA was not.
      However, neither peptide bound all of the HLA-DR molecules associated with
      antibiotic-refractory Lyme arthritis. Among 11 patients, 9 had T cell reactivity
      with OspA(161-170), 6 had responses to MAWD-BP(276-288), and 3 had reactivity
      with T-span7(58-70), but reactivity with the self-peptides was lower than that
      induced by the spirochetal epitope. Thus, there remains an association between
      OspA(165-173) and antibiotic-refractory Lyme arthritis, and infection-induced
      autoimmunity is an attractive hypothesis to explain this outcome. However,
      molecular mimicry due to sequence homology between OspA(165-173) and a human
      peptide seems unlikely to be the critical mechanism.

PMID- 17555821
TI  - Synthesis, characterisation and antimicrobial activity of copper(II) and
      manganese(II) complexes of coumarin-6,7-dioxyacetic acid (cdoaH2) and 4
      methylcoumarin-6,7-dioxyacetic acid (4-MecdoaH2): X-ray crystal structures of
      [Cu(cdoa)(phen)2].8.8H(2)O and [Cu(4-Mecdoa)(phen)2].13H2O (phen=1,10
      phenanthroline).
AB  - Two novel coumarin-based ligands, coumarin-6,7-dioxyacetic acid (1) (cdoaH(2))
      and 4-methylcoumarin-6,7-dioxyacetic acid (2) (4-MecdoaH(2)), were reacted with
      copper(II) and manganese(II) salts to give [Cu(cdoa)(H(2)O)(2)].1.5H(2)O (3),
      [Cu(4-Mecdoa)(H(2)O)(2)] (4), [Mn(cdoa)(H(2)O)(2)] (5) and [Mn(4
      Mecdoa)(H(2)O)(2)].0.5H(2)O (6). The metal complexes, 3-6, were characterised by
      elemental analysis, IR and UV-Vis spectroscopy, and magnetic susceptibility
      measurements and were assigned a polymeric structure. 1 and 2 react with Cu(II)
      in the presence of excess 1,10-phenanthroline (phen) giving
      [Cu(cdoa)(phen)(2)].8.8H(2)O (7) and [Cu(4-Mecdoa)(phen)(2)].13H(2)O (8),
      respectively. The X-ray crystal structures of 7 and 8 confirmed trigonal
      bipyramidal geometries, with the metals bonded to the four nitrogen atoms of the
      two chelating phen molecules and to a single carboxylate oxygen of the
      dicarboxylate ligand. The complexes were screened for their antimicrobial
      activity against a number of microbial species, including methicillin-resistant
      Staphylococcus aureus (MRSA), Escherichia coli and Candida albicans. The metal
      free ligands 1 and 2 were active against all of the microbes. Complexes 3-6
      demonstrated no significant activity whilst the phen adducts 7 and 8 were active
      against MRSA (MIC(80)=12.1microM), E. coli (MIC(80)=14.9microM) and Patonea
      agglumerans (MIC(80)=12.6microM). Complex 7 also demonstrated anti-Candida
      activity (MIC(80)=22microM) comparable to that of the commercially available
      antifungal agent ketoconazole (MIC(80)=25microM).

PMID- 17555822
TI  - Synthesis and characterization of di-phenyl-tin(IV)-salicyliden-ortho
      aminophenols: analysis of in vitro antitumor/antioxidant activities and molecular
      structures.
AB  - The one pot reactions carried among salicylaldehyde 1, ortho-aminophenols 2a-2g,
      and di-phenyl-tin(IV) oxide 3 led to seven di-phenyl-tin(IV) compounds 4a-4g in
      good yields (97-83%). All compounds were analyzed by IR, 1H, 13C, 119Sn NMR
      spectroscopy, mass spectrometry and elemental analyses; furthermore, in the case
      of compounds 4b, 4c, 4e and 4g by X-ray diffraction. Compounds 4a-4g were tested
      in vitro against six human tumor cell lines U251, PC-3, K-562, HCT-15, MCF-7 and
      SKLU-1 to assess their in vitro antitumor activity. The results suggest
      biological specificity towards U251, MCF-7 and SKLU-1 cells at doses below 2.5
      microM, which are lower than cis-platin IC50's in the three cell lines. Since the
      inhibitory concentration values for the series were alike to Ph(2)SnCl(2) is
      feasible that only the Ph(2)Sn moiety is responsible for those activities,
      further experiments are under research. Besides, 4a-4g were tested for their
      antioxidant efficiency in rat brain homogenate showing that 4g is more active
      (IC50=3.01 microM) than the flavone quercetin (natural antioxidant, IC50=4.11
      microM) on inhibition of thiobarbituric acid reactive substances (TBARS). The
      TBARS activity (IC50) correlates with the ortho-aminophenol substitutions and a
      linear combination among sigma Hammett, one bond tin coupling constants and tin
      chemical shifts against the measured IC(50-TBARS) was found. This correlation
      gave basis that the implied molecular variables can become trackers for the
      calculation of TBARS inhibitory concentrations in similar systems. Moreover,
      there seemed to be an inverse structure-response behavior among activities, since
      the 4g derivative is the less active compound for cytotoxic assays meanwhile it
      is the best in antioxidant tests.

PMID- 17555823
TI  - Long-term safety evaluation of a novel oxygen-coordinated niacin-bound chromium
      (III) complex.
AB  - Chromium (III) is an essential micronutrient required for normal protein, fat and
      carbohydrate metabolism, as well as helps insulin metabolize fat, turn protein
      into muscle and convert sugar into energy. A broad spectrum of research
      investigations including in vitro, in vivo and clinical studies demonstrated the
      beneficial effects of novel oxygen- coordinated niacin-bound chromium (III)
      complex (NBC) in promoting glucose-insulin sensitivity, lipid profile,
      cardioprotective ability and lean body mass. This study examined the long-term
      safety of NBC by orally administering either 0 or 25 ppm or the human equivalency
      dose of 1000 microg elemental chromium (III) as NBC per day for 52 consecutive
      weeks to male and female Sprague-Dawley rats. Animals of each group and each
      gender were sacrificed on 26, 39, or 52 weeks of treatment. Body weight, physical
      and ocular health, feed and water intake, selected organ weights as such and as a
      percentage of liver and brain weight, hepatic lipid peroxidation and DNA
      fragmentation, hematology and clinical chemistry, and histopathological
      evaluations were conducted. At 26, 39, or 52 weeks of treatment, body weight gain
      was significantly reduced by 7.7%, 8.1% and 14.9% in male rats, and 5.5%, 11.4%
      and 9.6% in female rats, respectively, in the NBC treatment groups. No
      significant changes were observed in hepatic lipid peroxidation and DNA
      fragmentation, hematology and clinical chemistry, and histopathological
      evaluation between control and NBC groups at these time points. These findings,
      thus far, are in agreement with the subchronic studies in terms of the safety of
      NBC.

PMID- 17555825
TI  - Therapeutic application of anti-arthritis, pain-releasing, and anti-cancer
      effects of bee venom and its constituent compounds.
AB  - Bee venom (BV) therapy (BVT), the therapeutic application of BV, has been used in
      traditional medicine to treat diseases, such as arthritis, rheumatism, pain,
      cancerous tumors, and skin diseases. BV contains a variety of peptides, including
      melittin, apamin, adolapin, the mast-cell-degranulating (MCD) peptide, enzymes
      (i.e., phospholipase [PL] A(2)), biologically active amines (i.e., histamine and
      epinephrine), and nonpeptide components which have a variety of pharmaceutical
      properties. BV has been reported to have anti-arthritis effects in several
      arthritis models. Melittin, a major peptide component of BV, has anti
      inflammatory and anti-arthritis properties, and its inhibitory activity on
      nuclear factor kappaB (NF-kappaB) may be essential for the effects of BV. The
      anti-nociceptive effects of BV have also been demonstrated in thermal, visceral,
      and inflammatory pain models. Apcupoint stimulation (apipuncture) therapy into
      subcutaneous region may be important in the BV-induced anti-nociceptive effects.
      Multiple mechanisms, such as activation of the central and spinal opiod receptor,
      and alpha(2)-adrenergic activity, as well as activation of the descending
      serotonergic pathway have been suggested. The inhibition of c-Fos expression in
      the spinal cord by BV apipuncture in several nociceptive models is also reported
      to be a possible mechanism. BV also has anti-cancer activity. The cell cytotoxic
      effects through the activation of PLA(2) by melittin have been suggested to be
      the critical mechanism for the anti-cancer activity of BV. The conjugation of
      cell lytic peptide (melittin) with hormone receptors and gene therapy carrying
      melittin can be useful as a novel targeted therapy for some types of cancer, such
      as prostate and breast cancer.

PMID- 17555826
TI  - The matrix metalloproteinases and CNS plasticity: an overview.
AB  - The matrix metalloproteinases (MMPs) are expressed in response to pro
      inflammatory stimuli and other triggers. The MMPs cleave numerous substrates
      including extracellular matrix components, cytokines and growth factors. In the
      CNS, while most studied in the context of disease, the many physiological
      functions of the MMPs are now becoming appreciated. This review provides an
      overview of the growing body of evidence for physiological roles of MMPs both in
      CNS development and in CNS plasticity in normal brain functioning, including
      learning and memory, as well as in CNS repair and reorganization as part of the
      neuroimmune response to injury.

PMID- 17555827
TI  - Genotyping of varicella-zoster virus strains after serial passages in cell
      culture.
AB  - There is little information in the literature about the stability of single
      nucleotide polymorphisms (SNP) used for genotyping of varicella-zoster virus
      (VZV) in sequencing studies. The objective of this study was to genotype VZV wild
      type and vaccine isolates representing the four major clades A, B, C and J before
      and after serial passages in cell culture. Eleven VZV strains were genotyped by
      sequencing of the open reading frames (ORF) 1, 21, 37, 50, 54 and 60 as well as
      by restriction fragment length polymorphism (RFLP) analysis of the ORFs 38 and 62
      after 1-16 passages in human embryonic lung fibroblasts (HELF). Results revealed
      no variations of nucleotide sequences in the ORFs 1, 21, 37, 50, 54 and 60 within
      16 cell culture passages. Additionally, there were no changes in the RFLP profile
      of the ORFs 38 and 62. In conclusion, VZV can be isolated in HELF and propagated
      for at least 16 passages before genotyping by sequencing without the risk of
      intra-strain variations. For rapid diagnostic identification of vaccine versus
      wild-type strains, the RFLP profile that is stable within several cell culture
      passages can be determined using DNA prepared from clinical specimens.

PMID- 17555828
TI  - The gamma cycle.
AB  - Activated neuronal groups typically engage in rhythmic synchronization in the
      gamma-frequency range (30-100 Hz). Experimental and modeling studies demonstrate
      that each gamma cycle is framed by synchronized spiking of inhibitory
      interneurons. Here, we review evidence suggesting that the resulting rhythmic
      network inhibition interacts with excitatory input to pyramidal cells such that
      the more excited cells fire earlier in the gamma cycle. Thus, the amplitude of
      excitatory drive is recoded into phase values of discharges relative to the gamma
      cycle. This recoding enables transmission and read out of amplitude information
      within a single gamma cycle without requiring rate integration. Furthermore,
      variation of phase relations can be exploited to facilitate or inhibit exchange
      of information between oscillating cell assemblies. The gamma cycle could thus
      serve as a fundamental computational mechanism for the implementation of a
      temporal coding scheme that enables fast processing and flexible routing of
      activity, supporting fast selection and binding of distributed responses. This
      review is part of the INMED/TINS special issue Physiogenic and pathogenic
      oscillations: the beauty and the beast, based on presentations at the annual
      INMED/TINS symposium (http://inmednet.com).

PMID- 17555824
TI  - Stress, ethanol, and neuroactive steroids.
AB  - Neurosteroids play a crucial role in stress, alcohol dependence and withdrawal,
      and other physiological and pharmacological actions by potentiating or inhibiting
      neurotransmitter action. This review article focuses on data showing that the
      interaction among stress, ethanol, and neuroactive steroids may result in plastic
      molecular and functional changes of GABAergic inhibitory neurotransmission. The
      molecular mechanisms by which stress-ethanol-neuroactive steroids interactions
      can produce plastic changes in GABA(A) receptors have been studied using
      different experimental models in vivo and in vitro in order to provide useful
      evidence and new insights into the mechanisms through which acute and chronic
      ethanol and stress exposure modulate the activity of GABAergic synapses. We show
      detailed data on a) the effect of acute and chronic stress on peripheral and
      brain neurosteroid levels and GABA(A) receptor gene expression and function; b)
      ethanol-stimulated brain steroidogenesis; c) plasticity of GABA(A) receptor after
      acute and chronic ethanol exposure. The implications of these new mechanistic
      insights to our understanding of the effects of ethanol during stress are also
      discussed. The understanding of these neurochemical and molecular mechanisms may
      shed new light on the physiopathology of diseases, such as anxiety, in which
      GABAergic transmission plays a pivotal role. These data may also lead to the need
      for new anxiolytic, hypnotic and anticonvulsant selective drugs devoid of side
      effects.

PMID- 17555830
TI  - Synergistic inhibition of pancreatic adenocarcinoma cell growth by trichostatin A
      and gemcitabine.
AB  - We investigated the ability of the histone deacetylase (HDAC) inhibitor
      trichostatin A (TSA) to interact with gemcitabine (GEM) in inducing pancreatic
      cancer cell death. The combined treatment with TSA and GEM synergistically
      inhibited growth of four pancreatic adenocarcinoma cell lines and induced
      apoptosis. This effect was associated with the induction of reactive oxygen
      species (ROS) by GEM, increased expression of the pro-apoptotic BIM gene by both
      TSA and GEM and downregulation of the 5'-nucleotidase UMPH type II gene by TSA.
      The expression of other genes critical for GEM resistance (nucleoside
      transporters, deoxycytidine kinase, cytidine deaminase, and ribonucleotide
      reductase genes) was not affected by TSA. The functional role of ROS in cell
      growth inhibition by GEM was supported by (i) a significantly reduced GEM
      associated growth inhibition by the free radical scavenger N-acetyl-L-cysteine,
      and (ii) a positive correlation between the basal level of ROS and sensitivity to
      GEM in 10 pancreatic cancer cell lines. The functional role of both Bim and 5'
      nucleotidase UMPH type II in cell growth inhibition by TSA and GEM was assessed
      by RNA interference assays. In vivo studies on xenografts of pancreatic
      adenocarcinoma cells in nude mice showed that the association of TSA and GEM
      reduced to 50% the tumour mass and did not cause any apparent form of toxicity,
      while treatments with TSA or GEM alone were ineffective. In conclusion, the
      present study demonstrates a potent anti-tumour activity of TSA/GEM combination
      against pancreatic cancer cells in vitro and in vivo, strongly supporting the use
      of GEM in combination with an HDAC inhibitor for pancreatic cancer therapy.

PMID- 17555832
TI  - Soluble CD40 ligand and atrial fibrillation: relationship to platelet activation,
      and endothelial damage/dysfunction.
AB  - Increased plasma soluble CD40L (sCD40L) is present in many cardiovascular
      diseases and predicts poor outcome, but levels in atrial fibrillation (AF) are
      unknown. Although the platelet is frequently cited as the source of sCD40L, this
      view is not universal. We hypothesised (a) raised sCD40L in non-rheumatic AF, and
      (b) that sCD40L correlates with platelet, but not endothelial, markers, thus
      suggesting a platelet origin. Plasma sCD40L, platelet marker soluble P-selectin
      and endothelial markers von Willebrand factor (vWf) and soluble E-selectin were
      measured by ELISA in 54 AF patients free of diabetes or major cardiovascular
      disease, and in 28 age/sex matched controls. Median (inter-quartile range) sCD40L
      in AF was 0.82 (0-4.8) ng/mL compared to 0.21 (0-5.5 ng/mL) in controls
      (p=0.0397). vWf and soluble P-selectin (p<0.005), but not soluble E-selectin,
      were raised in AF, but none of the indices inter-correlated significantly. We
      find that sCD40L is marginally raised in AF but the stimulus for this is unclear.
      The lack of clear correlation with relevant plasma markers suggests that the
      source is unlikely to be the endothelium or platelet alone.

PMID- 17555829
TI  - Raf kinases: function, regulation and role in human cancer.
AB  - The Ras-Raf-MAPK pathway regulates diverse physiological processes by
      transmitting signals from membrane based receptors to various nuclear,
      cytoplasmic and membrane-bound targets, coordinating a large variety of cellular
      responses. Function of Raf family kinases has been shown to play a role during
      organism development, cell cycle regulation, cell proliferation and
      differentiation, cell survival and apoptosis and many other cellular and
      physiological processes. Aberrations along the Ras-Raf-MAPK pathway play an
      integral role in various biological processes concerning human health and
      disease. Overexpression or activation of the pathway components is a common
      indicator in proliferative diseases such as cancer and contributes to tumor
      initiation, progression and metastasis. In this review, we focus on the
      physiological roles of Raf kinases in normal and disease conditions, specifically
      cancer, and the current thoughts on Raf regulation.

PMID- 17555831
TI  - Curcumin reverses breast tumor exosomes mediated immune suppression of NK cell
      tumor cytotoxicity.
AB  - An important characteristic of tumors is that they at some point in their
      development overcome the surveillance of the immune system. Tumors secrete
      exosomes, multivesicular bodies containing a distinct set of proteins that can
      fuse with cells of the circulating immune system. Purified exosomes from TS/A
      breast cancer cells, but not non-exosomal fractions, inhibit (at concentrations
      of nanograms per ml protein) IL-2-induced natural killer (NK) cell cytotoxicity.
      The dietary polyphenol, curcumin (diferuloylmethane), partially reverses tumor
      exosome-mediated inhibition of natural killer cell activation, which is mediated
      through the impairment of the ubiquitin-proteasome system. Exposure of mouse
      breast tumor cells to curcumin causes a dose-dependent increase in ubiquitinated
      exosomal proteins compared to those in untreated TS/A breast tumor cells.
      Furthermore, exosomes isolated from tumor cells pretreated with curcumin have a
      much attenuated inhibition of IL-2 stimulated NK cell activation. Jak3-mediated
      activation of Stat5 is required for tumor cytotoxicity of IL-2 stimulated NK
      cells. TS/A tumor exosomes strongly inhibit activation of Stat5, whereas the
      tumor exosomes isolated from curcumin-pretreated tumor cells have a lowered
      potency for inhibition of IL-2 stimulated NK cell cytotoxicity. These data
      suggest that partial reversal of tumor exosome-mediated inhibition of NK cell
      tumor cytotoxicity may account for the anti-cancer properties of curcumin.

PMID- 17555833
TI  - Isolated interrupted aortic arch, a rare cause of hypertension in adults.
AB  - Interrupted aortic arch (IAA) is a rare and usually lethal congenital
      malformation. Patients with complete IAA very rarely do reach adult age without
      previous surgical intervention. The present report describes a 26-year-old
      asymptomatic isolated IAA case with hypertension that was incidentally diagnosed.
      IAA just distal to the left subclavian artery and a markedly developed collateral
      circulation was demonstrated by cardiac catheterization and thoracic 3D magnetic
      resonance angiography. This case report was also interesting that only mild
      arterial hypertension of the upper extremities was incidentally found in the
      patient.

PMID- 17555834
TI  - Methodologies towards the development of an oligonucleotide microarray for
      determination of Salmonella serotypes.
AB  - A DNA-based microarray designed to detect somatic (O) and flagellar (H) antigens
      present in the five most commonly isolated Salmonella serovars within Canada was
      developed as an alternative to the traditional Kauffmann-White serotyping scheme
      currently used to serotype salmonellae. Short oligonucleotide probes were
      designed based on publicly available sequence data of selected genes responsible
      for O and H antigen biosynthesis. These targets included: antigen-specific
      sequences within the flagella (H) antigen phase 1 (fliC) and phase 2 (fljB) genes
      and somatic (O) antigen biosynthesis genes within the rfb cluster (Groups B-
      rfbJ, C1--wbaA, C2--rfbJ, D1--rfbS). A prototype microarray with 117 O and H
      antigen-specific probes and controls was used to assess probe performance against
      two pools of gene target PCR amplicons. A set of 31 of these antigen-specific
      probes (8 O and 23 H) with high specific signal and low non-specific signal were
      selected based on t-test (p-value <0.01) and log(2) ratio distribution analysis
      to create a prototype microarray. The microarray was tested against 16 Salmonella
      strains of known serotype. Based on the strains tested in this study, these
      probes successfully identified and differentiated 11 of the 12 antigens targeted.
      The prototype DNA-based typing microarray described here has the potential to be
      an automated alternative to the traditional antigen-antibody serotyping scheme
      currently used for Salmonella.

PMID- 17555835
TI  - Visual verbal working memory processing may be interfered by previously seen
      faces.
AB  - Processing and maintenance in working memory involve active attention allocation;
      consequently, it is possible that a recognition process could interfere with the
      performance of highly demanding working memory tasks. Event-related brain
      potentials (ERPs) were recorded while fourteen healthy male adults performed a
      visual verbal dual working memory task. Three conditions were examined: A)
      reference (with no preceding stimuli); B) happy, angry or neutral faces presented
      250 ms prior to task onset for 30 ms; and, C) visual noise control condition.
      Behavioral results showed that reaction times were significantly longer in the
      condition preceded by the presentation of faces, regardless of their emotional
      content. ERPs showed a predominantly right temporo-occipital negative component
      at around 170 ms during conditions B and C (higher amplitude in B), which
      probably reflects the pre-categorical structural encoding of the face. Succeeding
      task-onset, an early positive right temporo-parietal component (P380) appeared
      during condition B, probably reflecting a delayed reallocation of working memory
      attentional resources to carry out the task requirements. Afterwards, two other
      main fronto-parietal components were observed in the three conditions: a positive
      wave that peaked at around 410 ms, and a subsequent negative component (N585).
      This latter waveform reached a significantly higher amplitude during the
      reference condition (A) and was interpreted as mirroring the phonologic-lexical
      manipulation of the stimuli in working memory. These results suggest that early
      face detection could induce an attentional decrement that interfere a subsequent
      visual verbal working memory task performance. They also suggest that while face
      detection and facial emotional content analysis might be parallel processes, they
      are not onset-synchronized.

PMID- 17555836
TI  - Violent offending predicts P300 amplitude.
AB  - Prior work has consistently revealed a relationship between antisocial behavior
      and reduced P300 amplitude. Fewer studies have directly evaluated behavioral
      indices of aggression and P300, and those that have generally do not account for
      potential mediating variables such as age, intelligence, and behavioral task
      performance. The current study assessed the relationship between the total number
      of convicted violent and non-violent offenses and P300 in a sample of inmates
      from a medium security state prison. Violent offenses evidenced a robust negative
      relationship with P300 amplitude, whereas non-violent offenses did not.
      Additional analyses evaluated age, intelligence, and behavioral task performance
      as potential mediating variables. Only reaction time significantly predicted P300
      amplitude, and mediational analyses showed that this relationship did not account
      for the violent-offense/P300 relationship. Findings are discussed in terms of
      personality correlates and neurobiological process related to aggression. There
      is long-standing interest in the notion that antisocial behavior, and aggression
      in particular, involves neurobiologically-based deficits in information
      processing. Neuropsychological research has revealed that antisocial behavior is
      associated with impaired executive function (c.f. Morgan and Lilienfeld, 2000),
      and neuroimaging studies have consistently identified frontal lobe abnormalities
      among violent offenders (Goyer et al., 1994; Raine et al., 1997; Raine et al.,
      2000; Volkow et al., 1995). Furthermore, research using event-related brain
      potentials has indicated that antisocial behavior is associated with reduced P300
      responses to task-relevant stimuli in target detection tasks (e.g., Bauer et al.,
      1994; Iacono et al., 2003). These deficits may reflect inefficient neural
      processing of salient environmental stimuli (Donchin and Coles, 1988), which
      could potentially contribute to risk for antisocial deviance. Notably, antisocial
      behavior encompasses both violent and nonviolent transgressions. One unresolved
      issue is whether P300 amplitude is associated with both violent and non-violent
      forms of antisocial behavior, or more predominantly with aggressive forms of
      acting out. Some research has examined P300 response in aggressive individuals
      specifically (e.g., Barratt et al., 1997); this work has revealed that reduced
      P300 amplitude is selectively related to impulsive, but not instrumental,
      aggression. However, this work has not compared associations for aggressive
      versus non-aggressive offending behavior. Thus, the aim of the present study was
      to replicate and extend prior research on antisocial behavior and brain response
      by examining relations between violent and non-violent offenses and P300
      amplitude in a sample of adult male inmates. Our prediction was that reduced P300
      response would be associated more predominantly with a history of violent
      offending, and that this effect would be independent of age, intelligence, and
      task performance effects.

PMID- 17555837
TI  - Production and use of deuterated polyhydroxyoctanoate in structural studies of
      PHO inclusions.
AB  - This work reports on the biosynthesis of polyhydroxyalkanoates with medium chain
      length alkyl substituents in the side chain by Pseudomonas oleovorans using
      hydrogenated and deuterated substrates. These investigations aimed to obtain
      polyhydroxyalkanoates with varying degrees of deuterium substitution, and
      establish whether they are suitable analogues for structural investigation. In
      order to understand the formation and structure of inclusions in their native
      state, whole inclusions were isolated from microbial cells and were analysed
      using Small Angle Neutron Scattering. A contrast variation study was conducted on
      hydrogenated and deuterated inclusions of polyhydroxyoctanoate, as well as
      inclusions resulting from co-feeding or sequentially feeding different
      precursors. The data indicated a core/shell structure resulting from feeding
      hydrogenated followed by perdeuterated PHO precursor, and demonstrated the
      utility of this analysis for characterising chemically similar systems.

PMID- 17555838
TI  - Ethanol production from xylose by recombinant Saccharomyces cerevisiae expressing
      protein engineered NADP+-dependent xylitol dehydrogenase.
AB  - Effects of reversal coenzyme specificity toward NADP+ and thermostabilization of
      xylitol dehydrogenase (XDH) from Pichia stipitis on fermentation of xylose to
      ethanol were estimated using a recombinant Saccharomyces cerevisiae expressing
      together with a native xylose reductase from P. stipitis. The mutated XDHs
      performed the similar enzyme properties in S. cerevisiae cells, compared with
      those in vitro. The significant enhancement(s) was found in Y-ARSdR strain, in
      which NADP+-dependent XDH was expressed; 86% decrease of unfavorable xylitol
      excretion with 41% increased ethanol production, when compared with the reference
      strain expressing the wild-type XDH.

PMID- 17555839
TI  - High-level secretion of Pseudomonas fluorescens type I secretion system-dependent
      lipase in Serratia marcescens.
AB  - The type I secretion system-dependent lipase, TliA, of Pseudomonas fluorescens
      was successfully produced in quantity in Serratia marcescens by coexpressing its
      cognate ABC transporter, TliDEF. Compared with P. fluorescens and Escherichia
      coli, S. marcescens showed an outstanding capacity for the secretory production
      of TliA, which was done with the expression vectors available for use in E. coli,
      and no growth phase-dependency, which was unlike the typical feature of TOSS
      mediated protein secretion. Among the S. marcescens tested, the highest amount of
      TliA (approximately 2600 units ml(-1)) was achieved by S. marcescens KCTC 2798
      containing the expression plasmid pTliDEFA-223. Our results also suggest that
      strains of Serratia will provide a valuable opportunity for producing other
      extracellular TOSS-dependent proteins effectively as well as the TliDEF-dependent
      TliA in this study.

PMID- 17555840
TI  - Enrichment strategies for siRNA-transfected cells in an untransfected background.
AB  - Gene silencing experiments in difficult-to-transfect cells are often hampered by
      the presence of a background of untransfected cells. We present proof-of-concept
      data from two different strategies for enrichment of siRNA-transfected cells. In
      the first approach, a heterologous surface antigen is expressed from a plasmid
      that is co-transfected with an siRNA targeting an endogenous mRNA. The surface
      antigen is then used for enrichment of successfully transfected cells using
      antibody-coated magnetic particles. In the second strategy, a eukaryotic
      antibiotic resistance gene is expressed from a co-transfected plasmid. Addition
      of the corresponding antibiotic 24h after transfection results in killing of
      untransfected cells, which can be washed away. Elimination of untransfected cells
      will allow more accurate interpretation of the effects of gene silencing.

PMID- 17555841
TI  - The impact of PHB accumulation on L-glutamate production by recombinant
      Corynebacterium glutamicum.
AB  - Corynebacterium glutamicum, a gram-positive soil bacterium, has been used
      extensively for the industrial production of l-glutamate and other amino acids.
      In this study, an Escherichia coli-C. glutamicum shuttle expression plasmid
      harboring polyhydroxybutyrate (PHB) synthesis genes, phbCAB from Ralstonia
      eutropha, was constructed under the Ptrc promoter. C. glutamicum harboring this
      plasmid accumulated 3-13% PHB with a weight average molecular mass of 125,400 and
      a polydispersity of 11.3 when grown on glucose. PHB synthesis related enzyme
      activities including beta-ketothiolase (PhbA), acetoacetyl-CoA reductase (PhbB)
      and PHB synthase (PhbC) were found to be constitutively produced independent of
      IPTG. l-Glutamate production increased 39-68% in two C. glutamicum strains
      harboring PHB synthesis genes compared with their parent strains in shake flask
      experiments. In fermentor studies, the recombinant produced approximately 23%
      more l-glutamate compared with that of the wild type, and yielded less
      intermediate metabolites or by-products including alpha-ketoglutarate, l
      glutamine and lactate. These results suggested that the expression of phbCAB
      genes in C. glutamicum could help regulate glutamate production metabolism. This
      demonstrated that the expression of PHB synthesis genes has a positive effect on
      l-glutamate production in C. glutamicum.

PMID- 17555842
TI  - Comparative genomics reveals novel biochemical pathways.
AB  - How well do we understand which enzymes are involved in the primary metabolism of
      the cell? A recent study using comparative genomics and postgenomics approaches
      revealed a novel pathway in the most studied organism, Escherichia coli. The
      analysis of a new operon consisting of seven previously uncharacterized genes
      thought to be involved in the degradation of nucleic acid precursors shows the
      impact of comparative genomics on the discovery of novel pathways and enzymes.

PMID- 17555843
TI  - Comparison of tryptophan biosynthetic operon regulation in different Gram
      positive bacterial species.
AB  - The tryptophan biosynthetic operon has been widely used as a model system for
      studying transcription regulation. In Bacillus subtilis, the trp operon is
      primarily regulated by a tryptophan-activated RNA-binding protein, TRAP. Here we
      show that in many other Gram-positive species the trp operon is regulated
      differently, by tRNA(Trp) sensing by the RNA-based T-box mechanism, with T-boxes
      arranged in tandem. Our analyses reveal an apparent relationship between trp
      operon organization and the specific regulatory mechanism(s) used.

PMID- 17555844
TI  - Unconventional binding sites and receptors for VIP and related peptides PACAP and
      PHI/PHM: an update.
AB  - The 28-amino-acid neuropeptide VIP and related peptides PACAP and PHI/PHM
      modulate virtually all of the vital functions in the body. These peptides are
      also commonly recognized as major regulators of cell growth and differentiation.
      Through their trophic and cytoprotective functions, they appear to play major
      roles in embryonic development, neurogenesis and the progression of a number of
      cancer types. These peptides bind to three well-characterized subtypes of G
      protein coupled receptors: VPAC1 and VPAC2 share a common high affinity in the
      nanomolar range for VIP and PACAP; a third receptor type, PAC1, has been
      characterized for its high affinity for PACAP but its low affinity for VIP.
      Complex effects and pharmacological behaviors of these peptides suggest that
      multiple subtypes of binding sites may cooperate to mediate their function in
      target cells and tissues. In this complex response, some of these binding sites
      correspond to the definition of the conventional receptors cited above, while
      others display unexpected pharmacological and functional properties. Here we
      present potential clues that may lead investigators to further characterize the
      molecular nature and functions of these atypical binding species.

PMID- 17555845
TI  - Regulation of the NMDA receptor-mediated synaptic response by
      acetylcholinesterase inhibitors and its impairment in an animal model of
      Alzheimer's disease.
AB  - The cholinergic system is crucial for cognitive processes and the deficient
      acetylcholine (ACh) function has been implicated in Alzheimer's disease (AD).
      Inhibitors of acetylcholinesterase (AChE), which act to enhance cholinergic
      function by prolonging the action of endogenously released ACh, have been used as
      the major therapy of AD. To understand the functional roles of cholinergic
      enhancement in prefrontal cortex (PFC), a key brain region for cognition, we
      examined the impact of AChE inhibitors in PFC neurons on synaptic responses
      mediated by the NMDA receptor (NMDAR), an important player in learning and
      memory. We found that AChE inhibitors produced a strong and persistent reduction
      of the amplitude of NMDA receptor-mediated excitatory postsynaptic current (NMDAR
      EPSC). This effect was mainly mediated by nicotinic ACh receptors, and through a
      Ca(2+)-dependent mechanism. Inhibition of extracellular signal-regulated kinases
      (ERK) abolished the regulation of NMDAR function by AChE inhibitors, suggesting
      the involvement of ERK. In the transgenic mouse model of AD overexpressing mutant
      beta-amyloid precursor protein (APP), the effect of AChE inhibitors on NMDAR-EPSC
      was significantly impaired, which was associated with their diminished effect on
      ERK activation. Taken together, these results suggest that one of the key targets
      of endogenous ACh involved in cognition is the NMDAR-mediated transmission. Loss
      of the regulation of synaptic NMDAR responses by endogenous ACh may contribute to
      the cognitive deficiency in AD.

PMID- 17555846
TI  - Synthesis and antifungal activity of some new 3-hydroxy-2-(1-phenyl-3-aryl-4
      pyrazolyl) chromones.
AB  - Seven new 3-hydroxy-2-(1-phenyl-3-aryl-4-pyrazolyl) chromones 4a-g have been
      synthesized by the oxidation of 2-hydroxychalcone analogues of pyrazole 3a-g with
      hydrogen peroxide (H(2)O(2)) in KOH-MeOH by Algar Flynn Oymanda (AFO) reaction.
      The structures of the compounds 4 were established by the combined use of (1)H
      NMR, IR and mass spectra. All the seven compounds were tested in vitro for their
      antifungal activity against three phytopathogenic fungi, namely Helminthosporium
      species, Fusarium oxysporum and Alternaria alternata. Five compounds 4a, 4b, 4c,
      4e and 4f were associated with substantially higher antifungal activity than
      commercial antifungal compound Actidione (cycloheximide) against all three
      phytopathogenic fungi.

PMID- 17555847
TI  - Comment to "Aseptic meningitis after vaccination with L-Zagreb mumps strain
      virologically confirmed cases" faulty calculation of rates.

PMID- 17555848
TI  - Alpha interferon is a powerful adjuvant for a recombinant protein vaccine against
      foot-and-mouth disease virus in swine, and an effective stimulus of in vivo
      immune response.
AB  - The adjuvant effect of porcine interferon-alpha (PoIFN-alpha) was examined in
      swine vaccinated with a recombinant FMD protein vaccine named IgG-FMDV, which
      contains the swine IgG single heavy chain constant region and an immunogenic
      peptide of serotype O FMDV. The PoIFN-alpha gene was cloned into pcDNA3 vector
      and the recombinant plasmid was incorporated into cationic liposomes by a
      dehydration and rehydration procedure to use as an adjuvant, injected together
      with low-dose IgG-FMDV. This procedure resulted in strong induction of FMDV
      specific neutralizing antibody and significant T-cell-mediated immune responses,
      whereas only a modest humoral and cellular response was observed with low-dose
      vaccine alone. As an adjuvant for the protein vaccine, PoIFN-alpha induced strong
      inflammatory cytokines production in vivo and the results denoted that IFN
      adjuvant and our vaccines could drive the immune response toward Th1 type
      responses. The data of ELISA suggests that the recombinant protein vaccine
      synergizes with the IFN-adjuvant to produce endogenous IFN in vivo. In response
      to viral challenge, all control animals developed viremia and lesions, whereas
      all animals received IFN-adjuvant+IgG-FMDV were protected and nonstructural
      protein antibody in this group could not be detected by 14 days post-challenge
      (dpc). Our studies indicate that porcine IFN-alpha is a powerful adjuvant for
      recombinant FMD protein vaccine and could aid in vaccination against FMDV in
      swine.

PMID- 17555849
TI  - Evaluation of immune response to orally administered Sterne strain 34F2 anthrax
      vaccine.
AB  - Present animal vaccines against Bacillus anthracis infection are capable of
      inducing protective immunity. However, due to the route of administration, the
      vaccine has limited or no use in wildlife especially in rural areas of the world.
      Hence, an oral vaccine is needed for controlling this disease. For proof of
      concept we used the commercially available Sterne strain 34F2 vaccine mixed with
      oral scarifying agents. Although the immunological response as measured by ELISA
      in this group was not equal to the parenterally inoculated animals, the results
      indicate that the oral administration of this vaccine with oropharyngeal mucosa
      scarifying agents mixed with feed can induce immune responses in goats.

PMID- 17555850
TI  - Antibody persistence following booster vaccination against tick-borne
      encephalitis: 3-year post-booster follow-up.
AB  - In order to evaluate the long-term immunity 2 and 3 years after booster
      vaccination against tick-borne encephalitis (TBE) following time intervals 3
      years and longer since last TBE immunization, 195 (mean age 50.5+/-15.1 years)
      and 240 subjects (mean age 47.0+/-15.4 years), respectively, who had received a
      single booster dose in a preceding study, returned for a serological follow-up.
      Antibody concentrations were measured by neutralization test (NT) and ELISA.
      Protective TBE antibody levels (NT>or=10) were noted in 96% (187/195) of the
      subjects at year 2 and 97% (232/240) at year 3 post-booster. At both years, GMTs
      (NT) of all age groups were above detection limit (>or=2), showing GMT-NT of 54.5
      (95% CI: 47.7-62.4) and 69.1 (95% CI: 60.7-78.6), respectively. GMTs were
      significantly lower in vaccinees>or=50 years of age (p<0.001 for both years).
      Comparison of GMTs at years 2 and 3 post-booster vaccination with pre-booster
      values revealed similar antibody titers at all three reading points. Besides an
      expected rapid decline of TBE antibodies shortly after booster administration,
      the kinetic curve also suggested maintenance of high values of neutralizing TBE
      antibodies for a period longer than expected, thus confirming the recent
      recommendations regarding the extension of TBE booster intervals.

PMID- 17555851
TI  - Pre- or post-pandemic influenza vaccine?

PMID- 17555852
TI  - Testing nickel tolerance of Sorghastrum nutans and its associated soil microbial
      community from serpentine and prairie soils.
AB  - Ecotypes of Sorghastrum nutans from a naturally metalliferous serpentine
      grassland and the tallgrass prairie were assessed for Ni tolerance and their
      utility in remediation of Ni-polluted soils. Plants were inoculated with
      serpentine arbuscular mycorrhizal (AM) root inoculum or whole soil microbial
      communities, originating from either prairie or serpentine, to test their effects
      on plant performance in the presence of Ni. Serpentine plants had marginally
      higher Ni tolerance as indicated by higher survival. Ni reduced plant biomass and
      AM root colonization for both ecotypes. The serpentine AM fungi and whole
      microbial community treatments decreased plant biomass relative to uninoculated
      plants, while the prairie microbial community had no effect. Differences in how
      the soil communities affect plant performance were not reflected in patterns of
      root colonization by AM fungi. Thus, serpentine plants may be suited for
      reclamation of Ni-polluted soils, but AM fungi that occur on serpentine do not
      improve Ni tolerance.

PMID- 17555853
TI  - Seasonal temperatures have more influence than nitrogen fertilizer rates on
      cucumber yield and nitrogen uptake in a double cropping system.
AB  - Two-year greenhouse cucumber experiments were conducted to investigate seasonal
      effects on fruit yield, dry matter allocation, and N uptake in a double-cropping
      system with different fertilizer management. Seasonal effects were much greater
      than fertilizer effects, and winter-spring (WS) cucumber attained higher fruit
      yields and N uptake than autumn-winter (AW) cucumber due to lower cumulative air
      temperatures during fruit maturation in the AW season. Fertilizer N application
      and apparent N loss under recommended N management (Nmr) decreased by 40-78% and
      33-48% without yield loss compared to conventional N management (Nmt) over four
      growing seasons. However, there were no seasonal differences in N
      recommendations, taking into consideration seasonal differences in crop N demand,
      critical nutrient supply in the root zone and N mineralization rate.

PMID- 17555854
TI  - Natural attenuation of diesel aliphatic hydrocarbons in contaminated agricultural
      soil.
AB  - A diesel fuel spill at a concentration of 1 L m(-2) soil was simulated on a 12
      m(2) plot of agricultural land, and natural attenuation of aliphatic hydrocarbons
      was monitored over a period of 400 days following the spill after which the
      aliphatic hydrocarbon concentrations were found to be below the legal
      contamination threshold for soil. The main fraction of these compounds (95%)
      remained at the surface layer (0-10 cm). Shortly after the spill (viz. between
      days 0 and 18), evaporation was the main origin of the dramatic decrease in
      pollutant concentrations in the soil. Thereafter, soil microorganisms used
      aliphatic hydrocarbons as sources of carbon and energy, as confirmed by the
      degradation ratios found. Soil quality indicators, soil microbial biomass and
      dehydrogenase activity, regained their original levels about 200 days after the
      spill.

PMID- 17555855
TI  - Polycyclic aromatic hydrocarbons and their hydroxylated metabolites in fish bile
      and sediments from coastal waters of Colombia.
AB  - Sediments and fish bile collected from the Atlantic coastal waters of Colombia
      were analyzed for 16 parent polycyclic aromatic hydrocarbons (PAHs), and 23
      hydroxylated PAHs (OH-PAHs), respectively. Sediments contained overall mean
      SigmaPAH concentrations of 2090, 234 and 170 ng/g, dry wt, for Cartagena Bay,
      Caimanera Marsh, and Totumo Marsh, respectively. The mean concentration of the
      summed OH-PAHs in fish bile was 1250, 180 and 64.1 ng/g bile wt for Cartagena
      Bay, Caimanera Marsh, and Totumo Marsh, respectively. The results suggest that
      Cartagena Bay is heavily polluted by PAHs, and that exposure to high
      concentrations of PAHs together with other factors could contribute to the
      decreased health of fish living in this ecosystem. This is one of the first
      studies to describe the analysis of 23 individual OH-PAHs in fish bile, using
      authentic standards.

PMID- 17555856
TI  - Do wood mice (Apodemus sylvaticus L.) use food selection as a means to reduce
      heavy metal intake?
AB  - Food preference of wood mice from two with heavy metals polluted sites and two
      unpolluted sites was tested under laboratory and field conditions with two-way
      choice experiments. In the laboratory, wood mice preferred to eat acorns from
      unpolluted sites over acorns from polluted sites. Previous experience with
      polluted food had no influence on food choice. Preference was negatively related
      to acorn metal content. Furthermore, the nutrient content of the acorn endosperm
      was consistently lower in polluted sites. We therefore conclude that wood mice
      used absolute metal concentration in the acorn, nutrient content, or both as a
      food selection cue. The results of the laboratory experiment could not be
      confirmed under field conditions. We hypothesized that search time constraints
      due to the presence of predators, competitors and/or other stress factors in the
      field have prevented the mice to forage selectively.

PMID- 17555857
TI  - Psychosocial and pharmacological interventions for depressed adults in primary
      care: a critical review.
AB  - Primary care settings are the principal context for treating clinical depression,
      with researchers beginning to explore the efficacy of psychosocial and
      pharmacological treatments for depression within this infrastructure. Feasibility
      and process variables also are being assessed, including issues of cost
      effectiveness, viability of collaborative care models, predictors of treatment
      outcome, and effectiveness of treatment providers without specialized mental
      health training. The Agency for Health Care Policy and Research and American
      Psychiatric Association initially released guidelines for the treatment of
      depression in primary care [American Psychiatric Association, 1993. Practice
      Guidelines for major depressive disorder in adults. American Journal of
      Psychiatry, 150, 1-26., American Psychiatric Association, 2000. Practice
      Guideline for the treatment of patients with major depressive disorder
      (revision). American Journal of Psychiatry, 157, 1-45], however, a vast
      literature has accumulated over the past several years, calling for a systematic
      re-evaluation of the status of depression treatment in primary care. The present
      study provides a contemporary review of outcome data for psychosocial and
      pharmacological interventions in primary care and extends beyond AHCPR guidelines
      insofar as focusing on feasibility and process variables, including the training
      and proficiency of primary care treatment providers, cost-effectiveness of
      primary care interventions, and predictors of treatment response and relapse.
      Based on current guidelines, problem-solving therapy (PST-PC), interpersonal
      psychotherapy, and pharmacotherapy would be considered efficacious interventions
      for major depression, with cognitive-behavioral and cognitive therapy considered
      possibly efficacious. Psychotherapy and pharmacotherapy generally are of
      comparable efficacy, and both modalities are superior to usual care in treating
      depression. Methodological limitations and directions for future research are
      discussed.

PMID- 17555858
TI  - Counterintuitive and alternative moves choice in the Water Jug task.
AB  - MOVE problems, like the Tower of London (TOL) or the Water Jug (WJ) task, are
      planning tasks that appear structurally similar and are assumed to involve
      similar cognitive processes. Carder et al. [Carder, H.P., Handley, S.J., &
      Perfect, T.J. ( 2004). Deconstructing the Tower of London: Alternative moves and
      conflict resolution as predictors of task performance. The Quarterly Journal of
      Experimental Psychology 57a, 8, 1459-1483] showed that one predictor of TOL
      performance was the number of alternative move choices there were at a given
      point in the solution. In two experiments an individual move experienced on the
      WJ task was manipulated (perceptually consistent/counterintuitive) along with the
      number of alternative moves there were to choose between. A verification paradigm
      was employed in which participants made speeded judgements about the correctness
      of a move. Results showed performance was consistent with the application of a
      perceptual strategy accompanied by a process involving the evaluation of non
      redundant alternative moves. These are discussed in the context of recent
      research that has examined the impact of executive dysfunction on Water Jug
      performance [Colvin, M.K., Dunbar, K., & Grafman, J. (2001). The effects of
      frontal lobe lesions on goal achievement in the Water Jug task. Journal of
      Cognitive Neuroscience, 13, 1129-1147].

PMID- 17555859
TI  - A review of the current literature on aetiology and measurement methods of
      halitosis.
AB  - OBJECTIVES: This work reviews the current knowledge of aetiology and measurement
      methods of halitosis. DATA: Halitosis is an unpleasant or offensive odour
      emanating from the breath. The condition is multifactorial and may involve both
      oral and non-oral conditions. SOURCES: A private, monthly with keywords
      halitosis, malodo(u)r, (a)etiology, measurement, and management from Medline and
      Pubmed updated database of literature was reviewed. CONCLUSIONS: In approximately
      80-90% of all cases, halitosis is caused by oral conditions, defined as oral
      malodour. Oral malodour results from tongue coating, periodontal disease, peri
      implant disease, deep carious lesions, exposed necrotic tooth pulps,
      pericoronitis, mucosal ulcerations, healing (mucosal) wounds, impacted food or
      debris, imperfect dental restorations, unclean dentures, and factors causing
      decreased salivary flow rate. The basic process is microbial degradation of
      organic substrates. Non-oral aetiologies of halitosis include disturbances of the
      upper and lower respiratory tract, disorders of the gastrointestinal tract, some
      systemic diseases, metabolic disorders, medications, and carcinomas. Stressful
      situations are predisposing factors. There are three primary measurement methods
      of halitosis. Organoleptic measurement and gas chromatography are very reliable,
      but not very easily clinically implemented methods. The use of organoleptic
      measurement is suggested as the 'gold standard'. Gas chromatography is the
      preferable method if precise measurements of specific gases are required.
      Sulphide monitoring is an easily used method, but has the limitation that
      important odours are not detected. The scientific and practical value of
      additional or alternative measurement methods, such as BANA test, chemical
      sensors, salivary incubation test, quantifying beta-galactosidase activity,
      ammonia monitoring, ninhydrin method, and polymerase chain reaction, has to be
      established.

PMID- 17555860
TI  - 'Partitagin' a hemorrhagic metalloprotease from Hippasa partita spider venom:
      role in tissue necrosis.
AB  - The poisonous bite by Hippasa partita, a funnel web spider from the Indian
      subcontinent has been demonstrated to give rise to severe dermo- and myonecrosis.
      In this work a hemorrhagic metalloprotease, Partitagin was purified from H.
      partita venom by successive chromatography on Sephadex G-100, DEAE Sephadex A-50
      and Biosep DEAE columns. SDS-PAGE, reversed phase HPLC on a C(4) column, N
      terminal amino acid sequencing and MALDI-TOF mass spectrometry confirmed the
      homogeneity. Partitagin was assayed using fat free casein as substrate. EDTA,
      1,10-phenanthroline and cyanide, inactivated it irreversibly while, EGTA, PMSF,
      leupeptin, pepstatin and aprotinin did not inhibit. The presence of Zn(+2) was
      confirmed by atomic absorption spectrometry. Partitagin caused hemorrhage when
      tested in a mouse model. Light microscopy of skin tissue sections at the site of
      injection revealed extensive damage of extracellular matrix (ECM) in which the
      basement membrane surrounding blood vessels and capillaries showing signs of
      extensive destruction and also loss of vessel wall integrity. Similar intense
      damage was also noticed in the ECM of muscle tissue sections but with no damage
      caused to myocytes. Partitagin showed specificity of action on the components of
      ECM and degraded collagen type-IV and fibronectin but not collagen type-I.
      Partitagin was devoid of edema, myotoxicity and lethality. This is the first
      report on the isolation and characterization of a toxin from spider venom in the
      Indian subcontinent.

PMID- 17555861
TI  - Blue-green vomit.

PMID- 17555862
TI  - Pregnancy and delivery of a patient with Ivemark syndrome (with polysplenia).

PMID- 17555863
TI  - Adsorption of nutrients and cadmium by different minerals: experimental studies
      and modelling.
AB  - This work analyses cadmium sorption by natural vermiculite, zeolite, and pumice,
      which have been recently considered for their potential use in remediation of
      contaminated soils. Batch experiments were performed to investigate the
      interactions between the mineral surfaces and the main nutritive cations of
      Hoagland solution. In addition to their ameliorative effect of reducing metal
      mobility, these minerals are able to interact to different extents with various
      components of the nutrient solution and can change the availability of essential
      nutrients in solution. Therefore, the minerals were also exposed to a range of
      cadmium doses to compare their different affinities for this element and to
      analyse the cadmium-nutrient interactions. The results showed that the nutrient
      solution composition was significantly modified by contact with zeolite and
      vermiculite, and to a minor extent with pumice. The ionic equilibrium between the
      solid and aqueous phases was attained at several time points depending on the
      cation. Ammonium and potassium ions were almost entirely absorbed by zeolite,
      while in vermiculite endogenous magnesium ions were exchanged with the liquid
      phase calcium ions. The amount of cadmium adsorbed on mineral surfaces
      equilibrated with the nutrient solution showed the following sequence
      zeolite>vermiculite>pumice, and the cation concentrations of the fluid phase were
      sensitive to cadmium addition.

PMID- 17555864
TI  - Social Sciences and landscape analysis: opportunities for the improvement of
      conservation policy design.
AB  - This article develops a methodology aimed at generating a systematic social
      diagnosis of social and natural landscapes. The analytical process is divided
      into six easily replicable and causatively connected steps. The goal is two-fold:
      first, to present the inextricable connections between physical landscapes and
      the communities that occupy them. And second, to provide a fundamental tool to
      public policy designers that should simultaneously improve social acceptability
      of conservation policies and policy efficiency and effectiveness. Finally, this
      methodology is consciously heterogeneous from a theoretical perspective. This
      article puts together, in fruitful dialogue, contributions from varying places on
      the social theory spectrum: from political economy to poststructural theory.

PMID- 17555865
TI  - Investigations on unconventional hydrogen bonds in RNA binding proteins: the role
      of CH...O=C interactions.
AB  - We have investigated the roles played by C-H...O=C interactions in RNA binding
      proteins. There was an average of 78 CH...O=C interactions per protein and also
      there was an average of one significant CH...O=C interactions for every 6
      residues in the 59 RNA binding proteins studied. Main chain-Main chain (MM)
      CH...O=C interactions are the predominant type of interactions in RNA binding
      proteins. The donor atom contribution to CH...O=C interactions was mainly from
      aliphatic residues. The acceptor atom contribution for MM CH...O=C interactions
      was mainly from Val, Phe, Leu, Ile, Arg and Ala. The secondary structure
      preference analysis of CH...O=C interacting residues showed that, Arg, Gln, Glu
      and Tyr preferred to be in helix, while Ala, Asp, Cys, Gly, Ile, Leu, Lys, Met,
      Phe, Trp and Val preferred to be in strand conformation. Most of the CH...O=C
      interacting polar amino acid residues were solvent exposed while, majority of the
      CH...O=C interacting non polar residues were excluded from the solvent. Long and
      medium-range CH...O=C interactions are the predominant type of interactions in
      RNA binding proteins. More than 50% of CH...O=C interacting residues had a higher
      conservation score. Significant percentage of CH...O=C interacting residues had
      one or more stabilization centers. Sixty-six percent of the theoretically
      predicted stabilizing residues were also involved in CH...O=C interactions and
      hence these residues may also contribute additional stability to RNA binding
      proteins.

PMID- 17555866
TI  - Expression of 11beta-hydroxysteroid-dehydrogenase 2 in Sertoli cells of boar
      testes.
AB  - 11beta-Hydroxysteroid-dehydrogenase 2 (11beta-HSD2) activity occurs in boar
      testes but it is not known which cell types express 11beta-HSD2 mRNA and protein.
      Therefore, testes samples were taken from mature boars. For immunocytochemistry
      and Western blot pig-specific antibodies were raised against a 10-amino acid
      peptide corresponding to amino acids 391-400 of the coding sequence. Quantitative
      PCR was performed in testis homogenates and additionally RT-PCR in samples
      collected by UV-single cell microdissection. Data show that in interstitial
      tissue 11beta-HSD2 is expressed in Leydig cells and additionally in blood
      capillaries. In tubuli, 11beta-HSD2 primarily is formed in Sertoli cells whereas
      occurrence in spermatogonia could not be definitely proven. Because
      glucocorticoid receptors were never found in boar Leydig cells, it is concluded
      that the expression of 11beta-HSD2 in several types of cells forms consecutive
      lines of defense to protect spermatogonia against glucocorticoid-induced
      apoptosis.

PMID- 17555867
TI  - Glucocorticoids in the control of neuroinflammation.
AB  - Glucocorticoids are a class of steroid hormones that are endowed with profound
      anti-inflammatory and immunosuppressive activities. Endogenous glucocorticoids
      are key players in the modulation of the immune system and establish an endocrine
      basis of many inflammatory diseases. In addition, synthetic glucocorticoids are
      amongst the most commonly prescribed drugs worldwide for the treatment of
      autoimmune disorders. In this review we summarize our present knowledge on the
      mechanisms by which glucocorticoids impact on multiple sclerosis (MS), a highly
      prevalent neuroinflammatory disease, and its animal model experimental autoimmune
      encephalomyelitis (EAE). In spite of the new methodologies that have become
      available during recent years, we are still far from a comprehensive picture of
      the mechanism by which glucocorticoids control neuroinflammation.

PMID- 17555868
TI  - Estrogen-responsive genes newly found to be modified by TCDD exposure in human
      cell lines and mouse systems.
AB  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) can induce estrogenic action or
      inhibit estrogen-induced effects in various tissues because of aryl hydrocarbon
      receptor (AhR)-estrogen receptor (ER) cross-talk. In order to identify the
      biomarkers of TCDD endocrine disruption, we screened estrogen-responsive genes
      modified by TCDD exposure using specific cDNA microarrays spotted with estrogen
      responsive genes. MCF-7 human breast carcinoma cells and RL95-2 human endometrial
      carcinoma cells were exposed to TCDD, and an analysis of their gene expression
      revealed 32 genes exhibiting a significant change. The mRNA expression levels of
      27 genes were subsequently verified using real-time RT-PCR. Among these genes,
      bioinformatic analyses indicated that insulin-like growth factor-binding protein
      5 (IGFBP5) gene expression might be influenced by estrogen status. In our animal
      experiments, IGFBP5 was also shown to be responsive to TCDD exposure in mouse
      fetuses in utero. These results suggest that TCDD affects the expression levels
      of a series of estrogen-responsive genes, and follow-up fetal studies in mice
      indicated that IGFBP5 is useful as a biomarker of TCDD activity.

PMID- 17555869
TI  - Refolding of misfolded mutant GPCR: post-translational pharmacoperone action in
      vitro.
AB  - All reported GnRH receptor mutants (causing human hypogonadotropic hypogonadism)
      are misfolded proteins that cannot traffic to the plasma membrane.
      Pharmacoperones correct misfolding and rescue mutants, routing them to the plasma
      membrane where they regain function. Because pharmacoperones are often
      peptidomimetic antagonists, these must be removed for receptor function after
      rescue; in vivo this necessitates pulsatile pharmacoperone administration. As an
      antecedent to in vivo studies, we determined whether pharmacoperones need to be
      present at the time of synthesis or whether previously misfolded proteins could
      be refolded and rescued. Accordingly, we blocked either protein synthesis or
      intra-cellular transport. Biochemical and morphological studies using 12 mutants
      and 10 pharmacoperones representing three different chemical classes show that
      previously synthesized mutant proteins, retained by the quality control system
      (QCS), are rescued by pharmacoperones, showing that pharmacoperone administration
      in vivo likely need not consider whether the target protein is being synthesized
      at the time of drug administration.

PMID- 17555870
TI  - Cerebral necrosis after 25Gy radiotherapy in childhood followed 28 years later by
      54Gy radiotherapy.
AB  - The development of brain necrosis is life-long risk of repeat radiation therapy,
      even after a long time interval and a moderate radiation dose. We report on a 34
      year-old patient who had prophylactic cranial irradiation with 25Gy and adjuvant
      chemotherapy in childhood for leukaemia and in adulthood, 28 years later,
      therapeutic radiotherapy with 54Gy for an atypical (WHO grade II) meningioma.
      About 2 years later he developed a contrast-enhancing lesion on MRI-scan that was
      indicative of a tumor according to a thallium-201 ((201)Tl) SPECT scan.
      Histopathology of the operated contrast-enhancing lesion showed extensive
      radionecrosis. Radiation necrosis is a small but serious risk after repeat
      radiation therapy, even after a very long-term interval, the delivery of small
      fractions and an average cumulative total dose. Patients undergoing repeat
      radiotherapy therefore need to be followed life-long for potential late radiation
      toxicity.

PMID- 17555871
TI  - Relationship between DNA damage and total antioxidant capacity in patients with
      transitional meningioma.
AB  - PURPOSE: The purpose of this study was to assess oxidative DNA damage and total
      antioxidant capacity (TAC) in patients with transitional meningioma (TM) and to
      compare the results with normal brain tissues. PATIENTS AND METHODS: Oxidative
      DNA damage and TAC were evaluated in TM extracted from 22 patients and in normal
      brain tissues of 15 subjects who underwent autopsy within first 4h of death.
      Oxidative DNA damage was assessed by measuring 8-hydroxy-2-deoxyguanosine (8-OH
      dG) using the 8-OH-dG enzyme immunoassay kit, a quantitative assay for 8-OH-dG,
      and TAC was analyzed using the ImAnOx colorimetric test system for the
      determination of antioxidative capacity. The results were compared between two
      groups and any correlation between 8-OH-dG and TAC was sought. RESULTS: The
      median level of TAC in TM (135nmol/gwet tissue) was remarkably lower than in
      normal brain tissue (298nmol/gwet tissue). The difference was statistically
      significant (p=0.00001). In contrast, oxidative DNA damage was significantly
      higher in patients with TM (71.61ng/gwet tissue) than in controls (34.71ng/gwet
      tissue). Again, the difference was statistically significant (p=0.00001). We also
      found a negative correlation between oxidative DNA damage and TAC (p<0.001).
      CONCLUSION: These findings show that the degree of oxidative DNA damage is
      increased and TAC is decreased in TM and oxidative DNA damage is negatively
      correlated with the levels of TAC.

PMID- 17555872
TI  - Superficial siderosis due to a lumbar ependymoma mimicking adult-onset
      spinocerebellar ataxia.
AB  - Superficial siderosis (SS), as a result of chronic subarachnoid haemorrhage and
      haemosiderin deposition on the leptomeninges and subpial layers of the brain,
      cerebellum and spinal cord, can cause ataxia, pyramidal tract lesions and hearing
      deficits. In cases with not pronounced hearing impairment adult-onset
      spinocerebellar ataxia can be considered as a differential diagnostic
      alternative. We report a similar case where the diagnosis of SS was established
      by means of gradient echo MRI sequences 5 years after symptom onset. A bleeding
      lumbar ependymoma was identified as a source of haemorrhage. Surgical tumor
      resection stopped any further disease progression. Our report underlines that
      clinicians should be aware of the clinical features and diagnostic pitfalls of
      SS. Time of diagnosis and neurosurgical intervention can essentially influence
      the patients' prognosis.

PMID- 17555873
TI  - Diosgenin, a naturally occurring steroid [corrected] saponin suppresses 3-hydroxy
      3-methylglutaryl CoA reductase expression and induces apoptosis in HCT-116 human
      colon carcinoma cells.
AB  - A growing body of experimental evidence suggests the therapeutic potential of
      diosgenin, a steroid [corrected] saponin against several cancers. However,
      precise molecular and cellular mechanisms underlying the modes of action of this
      compound against colon cancer remain only partially understood. In this study, we
      investigated if the anticancer mechanism of diosgenin in HCT-116 human colon
      carcinoma cells involves modulation in the expression of 3-hydroxy-3
      methylglutaryl Co-enzyme A (HMG-CoA) reductase, the rate-limiting enzyme of the
      cholesterol biosynthetic pathway. Diosgenin treatment resulted in a dose
      dependent decrease in the viability and growth of HCT-116 cells. The IC(50)
      cytotoxic dose of diosgenin in HCT-116 was approximately 35 microM after 24h,
      while concentrations of approximately 32 microM or greater decreased the percent
      viable cells by 50%. Higher doses of diosgenin (30-40 microM) effectively
      inhibited recovery of cells for up to 24h post-treatments. At sub-cytotoxic
      doses, diosgenin induced a dose-dependent increase in apoptotic demise. In part,
      the apoptotic mechanism was through the cleavage of the 116 kDa poly (ADP-ribose)
      polymerase protein to the 85kDa fragment. The expression of HMG-CoA reductase at
      both mRNA and protein levels was significantly lowered by increasing
      concentrations of diosgenin. This was accompanied by a concomitant dose-dependent
      decrease in the expression of p21 ras and beta-catenin. In conclusion, our data
      demonstrates that the food saponin, diosgenin is a potent inhibitor of HCT-116
      human colon carcinoma cells by growth inhibition and induction of apoptosis.
      Importantly, our result identifies that the growth suppressive or apoptotic
      activity of diosgenin may involve cholesterol homeostasis.

PMID- 17555874
TI  - A novel solid phase extraction procedure on Amberlite XAD-1180 for speciation of
      Cr(III), Cr(VI) and total chromium in environmental and pharmaceutical samples.
AB  - Due to the toxicity of chromium, species depend on their chemical properties and
      bioavailabilities, speciation of chromium is very important in environmental
      samples. A speciation procedure for chromium(III), chromium(VI) and total
      chromium in environmental samples is presented in this work, prior to flame
      atomic absorption spectrometric determination of chromium. The procedure is based
      on the adsorption of Cr(III)-diphenylcarbazone complex on Amberlite XAD-1180
      resin. After oxidation of Cr(III), the developed solid phase extraction system
      was applied to determinate the total chromium. Cr(III) was calculated as the
      difference between the total Cr content and the Cr(VI) content. The analytical
      conditions for the quantitative recoveries of Cr(VI) on Amberlite XAD-1180 resin
      were investigated. The effects of some alkaline, earth alkaline, metal ions and
      also some anions were also examined. Preconcentration factor was found to be 75.
      The detection limits (LOD) based on three times sigma of the blank (N: 21) for
      Cr(VI) and total chromium were 7.7 and 8.6 microg/L, respectively. Satisfactory
      results for the analysis of total chromium in the stream sediment (GBW7310)
      certified reference material for the validation of the presented method was
      obtained. The procedure was applied to food, water and pharmaceutical samples
      successfully.

PMID- 17555875
TI  - Unmyelinated visceral afferents exhibit frequency dependent action potential
      broadening while myelinated visceral afferents do not.
AB  - Sensory information arising from visceral organ systems is encoded into action
      potential trains that propagate along afferent fibers to target nuclei in the
      central nervous system. These information streams range from tight patterns of
      action potentials that are well synchronized with the sensory transduction event
      to irregular, patternless discharge with no clear correlation to the sensory
      input. In general terms these afferent pathways can be divided into unmyelinated
      and myelinated fiber types. Our laboratory has a long standing interest in the
      functional differences between these two types of afferents in terms of the
      preprocessing of sensory information into action potential trains (synchrony,
      frequency, duration, etc.), the reflexogenic consequences of this sensory input
      to the central nervous system and the ionic channels that give rise to the
      electrophysiological properties of these unique cell types. The aim of this study
      was to determine whether there were any functional differences in the somatic
      action potential characteristics of unmyelinated and myelinated vagal afferents
      in response to different rates of sensory nerve stimulation. Our results showed
      that activity and frequency-dependent widening of the somatic action potential
      was quite prominent in unmyelinated but not myelinated vagal afferents. Spike
      broadening often leads to increased influx of Ca(2+) ions that has been
      associated with a diverse range of modulatory mechanisms both at the cell body
      and central synaptic terminations (e.g. increased neurotransmitter release.) We
      conclude that our observations are indicative of fundamentally different
      mechanisms for neural integration of sensory information arising from
      unmyelinated and myelinated vagal afferents.

PMID- 17555876
TI  - Morphology, mechanical properties and viability of encapsulated cells.
AB  - The morphological and mechanical properties of encapsulated yeast cells
      (Saccharomyces cerevisiae) have been investigated by atomic force microscopy
      (AFM). Single living cells have been coated through the alternate deposition of
      oppositely charged polyelectrolyte (PE) layers. The properties of cells coated by
      different numbers of PE layers and from PE solutions of different ionic strength
      have been investigated. AFM imaging indicates an increase in PE coating stability
      when decreasing the solution ionic strength. The Young's moduli of the different
      examined systems have been evaluated through a quantitative analysis of force
      distance curves by using the Hertz-Sneddon model. The analysis indicates an
      increase in hybrid system stiffness when lowering the ionic strength of the PE
      solution. An evaluation of the viability of encapsulated cells was obtained by
      confocal laser scanning microscopy (CLSM) measurements. CLSM analysis indicates
      that cells preserve their subcellular structure and duplication capability after
      encapsulation. By coupling AFM and CLSM data, a correlation between local
      stiffness and duplication rate was obtained.

PMID- 17555877
TI  - Effect of stiffness of multi-level hierarchical attachment system on adhesion
      enhancement.
AB  - Geckos are known for their remarkable ability to cling on and detach from
      ceilings and walls using a unique attachment system. Their foot pads are covered
      by a large number of small hair (setae) that contain many branches per seta with
      a lower level of spatulae. This hierarchical structure gives the gecko
      adaptability to create a large real area of contact with rough surfaces. In this
      study, using the three-level hierarchical model recently developed to simulate a
      gecko seta contacting with random rough surface, the effects of spring stiffness
      and number of springs on the adhesion enhancement of multi-level hierarchical
      model are investigated. One- and three-level hierarchically structured spring
      models with different spring stiffnesses and number of springs on each level in
      contact with various rough surfaces are considered. The efficiency of attachment
      the adhesion coefficient, the adhesion force, the number of contacts and the
      adhesion energy-for the three-level models with different stiffness is
      investigated in contact with different rough surfaces.

PMID- 17555878
TI  - Nitric oxide induces apoptosis in cutaneous T cell lymphoma (HuT-78) by
      downregulating constitutive NF-kappaB.
AB  - Constitutive active NF-kappaB have been shown to protect cutaneous T cell
      lymphoma (CTCL) cells from apoptosis. In the present study, we have studied the
      cytotoxic potential of nitric oxide generating compound, sodium nitroprusside
      (SNP) on CTCL cell line, HuT-78. Treatment of cells with SNP resulted in decrease
      in mitochondrial membrane potential, cytochrome c release, activation of caspase
      3 and poly (ADP ribose) polymerase cleavage. SNP treatment inhibited activation
      of NF-kappaB in a concentration dependent manner. SNP increased the expression of
      IkappaBalpha without affecting the phosphorylation of IkappaBalpha.
      Downregulation of NF-kappaB by SNP decreased p65 nuclear translocation as evident
      by confocal fluorescence microscopy. Further it was found that SNP treatment
      caused downregulation of Bcl-2 family member (Bcl-xl) in HuT-78 cells. Thus, we
      have provided evidence that SNP induces apoptosis in CTCL cell line, HuT-78 by
      downregulating constitutive NF-kappaB and thereby Bcl-xl expression.

PMID- 17555879
TI  - Clioquinol and vitamin B12 (cobalamin) synergistically rescue the lead-induced
      impairments of synaptic plasticity in hippocampal dentate gyrus area of the
      anesthetized rats in vivo.
AB  - Lead (Pb(2+)) exposure in development induces impairments of synaptic plasticity
      in the hippocampal dentate gyrus (DG) area of the anesthetized rats in vivo. The
      common chelating agents have many adverse effects and are incapable of
      alleviating lead-induced neurotoxicity. Recently, CQ, clioquinol (5-chloro-7-iodo
      8-hydroxy-quinoline), which is a transition metal ion chelator and/or ionophore
      with low affinity for metal ions, has yielded some promising results in animal
      models and clinical trials related to dysfunctions of metal ions. In addition, CQ
      associated side effects are believed to be overcome with vitamin B12 (VB12)
      supplementation. To determine whether CQ treatment could rescue impairments of
      synaptic plasticity induced by chronic Pb(2+) exposure, we investigated the
      input/output functions (I/Os), paired-pulse reactions (PPRs) and long-term
      potentiation (LTP) of different treatment groups in hippocampal DG area of the
      anesthetized rat in vivo by recording field potentials and measured hippocampal
      Pb(2+) concentrations of different treatment groups by PlasmaQuad 3 inductive
      coupled plasma mass spectroscopy. The results show: CQ alone does not rescue the
      lead-induced impairments of synaptic plasticity in hippocampal DG area of the
      anesthetized rats in vivo; VB12 alone partly rescues the lead-induced impairments
      of LTP; however the co-administration of CQ and VB12 totally rescues these
      impairments of synaptic plasticity and moreover, the effects of CQ and VB12 co
      administration are specific to the lead-exposed animals.

PMID- 17555881
TI  - A proposed fairer method for conducting rofecoxib trials.
AB  - In this communication, a new plan will be proposed for the conductance of
      rofecoxib [Vioxx] trials because the current system of individual trials is
      considered to be irretrievably flawed and grossly unfair. The ideas about
      rofecoxib trials stem from a different paradigm to explain COX-2 inhibitor
      (coxib)-induced myocardial infarctions. This model for coxibs is based on the
      position that coxib-induced infarctions basically are "regular" infarctions, and
      thus differs from the apparent current position that coxib-induced infarctions
      are a "special" type of infarction. Three major problems with the current system
      of rofecoxib trials are proposed: presently used methods of separating out
      rofecoxib-induced infarctions are invalid, it is difficult to separate out with
      surety the half of rofecoxib-related infarctions which are rofecoxib-induced, and
      determining together at rofecoxib trials the two issues of whether an infarction
      is rofecoxib-induced and whether Merck handled rofecoxib properly leads to
      unfairness. The new plan bypasses these problems by bypassing the issue of
      determining at trial whether individual infarctions are rofecoxib-induced. In
      essence, the plan is a voluntary process designed to result in a class
      settlement. Plaintiffs are benefited mainly because they do not have to establish
      individually whether their infarctions are rofecoxib. Merck would benefit because
      its voluntary acceptance of the plan would be in accord with Merck's position it
      acted ethically with rofecoxib, and the plan has several factors to reduce
      significantly the overall level of recompense.

PMID- 17555880
TI  - Intracerebroventricular administration of an endothelin ETB receptor agonist
      increases expression of tissue inhibitor of matrix metalloproteinase-1 and -3 in
      rat brain.
AB  - Production of tissue inhibitors of matrix metalloproteinases (TIMPs), a family of
      secreted proteins with inhibitory actions on matrix metalloproteinases (MMPs), is
      up-regulated following nerve injuries and is suggested to have protective effects
      against MMP-mediated tissue damages. To clarify the extracellular signals
      involved in TIMP production in the brain, the effects of endothelins (ETs), a
      family of vasoconstricting peptides, were examined. I.c.v. administration of 500
      pmol/day Ala(1,3,11,15)-ET-1, an ET(B) receptor agonist, increased the level of
      TIMP-1 mRNA in rat hippocampus, caudate-putamen and cerebrum. Ala(1,3,11,15)-ET-1
      increased the level of TIMP-3 mRNA in the cerebrum, but not in the hippocampus or
      caudate-putamen. TIMP-2 mRNA was not affected in these brain regions.
      Ala(1,3,11,15)-ET-1 also stimulated the production of TIMP-1 and TIMP-3 proteins
      in the cerebrum. Immunohistochemical observations in the hippocampi of
      Ala(1,3,11,15)-ET-1-infused rats showed that NeuN-positive neurons and glial
      fibrillary acidic protein-positive astrocytes were immunoreactive for TIMP-1. In
      the cerebrum, astrocytes had TIMP-1 and TIMP3 reactivity, but neurons did not. In
      rat cultured astrocytes, both 100 nM Ala(1,3,11,15)-ET-1 and ET-1 increased the
      mRNA levels and protein release of TIMP-1 and TIMP-3 mRNAs. The effects of ET-1
      on astrocytic TIMP-1 and TIMP-3 mRNAs were inhibited by BQ788, an ET(B)
      antagonist. These findings indicate that activation of brain ET(B) receptors
      causes production of TIMP-1 and TIMP-3, and suggest the involvement of astrocytes
      in ET-induced TIMP production.

PMID- 17555882
TI  - Trans-coronary transplantation may be an optimal route in cellular
      cardiomyoplasty with stem cells.
AB  - Myocardial infarction is the leading cause of congestive heart failure and death
      in the industrialized world. However, the intrinsic repair mechanism of the
      injured heart and current therapeutic means are inadequate to regenerate lost
      myocardium. Recent interests focused on cellular cardiomyoplasty which is an
      outside intervention to support the reparative process in the heart through
      transplantation of stem/progenitor cells. Cellular myocardioplasty with stem
      cells is a possible option to reverse the adverse hemodynamic and neurohormonal
      imbalance after myocardial infarction. Experimental studies and clinical trials
      suggest that cellular cardiomyoplasty with stem/progenitor cells may improve
      cardiac function and prevent ventricular remodeling of the injured heart.
      Although the mechanisms are still in intensive debate, cellular cardiomyoplasty
      with stem cells has already been introduced into the clinical settings. However,
      it is an important challenge how donor cells are delivered to the targeted area.
      In early studies in animals, intramyocardial injection of stem cells after
      thoracotomy is the main transplantation route which is not suitable to most
      patients in clinical settings. Then the catheter-based infusion of stem cells is
      clinically introduced and rapidly developed because of its safety, convenience
      and micro-invasion. We hypothesize that catheter-based transplantation with stem
      cells may be a promising means to treat ischemic heart diseases in the future in
      clinical settings.

PMID- 17555883
TI  - A rational connection of inflammation with peripheral arterial disease.
AB  - Peripheral arterial disease (PAD) includes a wide range of manifestations in the
      lower limb, from asymptomatic to symptomatic disease ranging from intermittent
      claudication to critical limb ischemia, with ulcers, rest pain, or gangrene. It
      is manifestation of generalized atherosclerosis and this is clearly shown by the
      high prevalence of coexistence coronary and cerebral arterial disease in these
      patients. The cumulative findings on molecular and cellular biology have
      dramatically changed our concept of atherosclerotic disease. Recently, it has
      become clear that inflammation is fundamental to the process of atherosclerosis.
      Although the relation between inflammation and PAD is not well characterized, the
      emerging data demonstrated that PAD is a common manifestation of atherosclerosis
      that is associated with a systemic inflammation. The most important risk factors
      for PAD are similar to those of atherosclerotic disease elsewhere: age, male sex,
      diabetes mellitus, smoking, hypertension, hyperlipidemia, and hereditary factors.
      Serum levels of inflammatory markers, especially after exercise, have been found
      to be higher in patients with PAD than in controls, and associated with prognosis
      as well as restenosis in patients with PAD after revascularization. In the
      general United States adult population, inflammation is independently associated
      with PAD in a cross-sectional, nationally large representative sample. All of
      those evidences indicate that PAD is one aspect of atherosclerosis, a disease
      rationally connects with inflammation, which may further change our preventive
      and therapeutic strategies.

PMID- 17555884
TI  - Loss of IQ in the ICU brain injury without the insult.
AB  - Critically ill patients are at high risk of developing serious neurological
      dysfunctions including delirium and long-term neurocognitive impairment. Here a
      novel mechanism is proposed for this highly deleterious condition. A growing body
      of evidence has shown that critical illness and its treatment can lead to de novo
      cerebral atrophy including white and grey matter abnormalities, delirium, and
      neurocognitive decline. In healthy individuals, normal and consistent
      connectivity between the posterior parietal cortex (PPC), medial temporal lobe
      (MTL) and prefrontal cortex (PFC) maintains consciousness and normal cognitive
      functioning. The circuit is innervated, activated and maintained by the ascending
      reticular activating system (ARAS) arising from the brainstem. As elderly
      individuals begin to show signs of grey matter atrophy in the PPC, MTL and PFC,
      functional connectivity between these regions remains intact; however, the
      strength of the connections is no longer robust as it once was in the healthy
      CNS. This circuit continues to be activated and maintained via the ARAS.
      Individuals treated in the ICU are subject to a number of medical and
      pharmacological challenges which may disrupt normal CNS connectivity. Serious
      illnesses such as sepsis, acute respiratory distress syndrome (ARDS), and acute
      lung injury (ALI), as well as sedative and analgesic medications commonly
      prescribed in the ICU have the potential to disrupt the functional link in the
      circuit described above. Minor fluctuations in the ARAS (i.e. hyper or hypo
      activation) may be sufficient in elderly individuals to cause a disruption which
      surpasses the critical threshold of functional connectivity necessary to maintain
      normal (i.e. non-delirious) consciousness. In combination with exposure to other
      ICU related threats to neurocognitive function, prolonged decoupling of this
      circuit may lead to deleterious neurodegenerative consequences such as
      excitotoxicity. Over time this has the potential to result in apoptosis and long
      term cognitive impairment. Delirium appears to be a good candidate for the causal
      mechanism of ICU related cognitive decline and may be a critical point of
      intervention.

PMID- 17555885
TI  - A novel vicious cycle cascade in tumor chemotherapy.
AB  - Dendritic cells (DCs) play a critical role in both the cellular and humoral
      immune response to tumor cells. The participation of co-stimulator molecules on
      DCs is of vital importance for full activation of T cells. Conventional tumor
      chemotherapy cannot only induce apoptosis of malignant cells, but also do harm to
      benign DCs. Expression levels of co-stimulatory molecules (especially CD80 and
      CD86) are downregulated during anticancer drug treatment. These DCs are defective
      in their antigen-presenting function being lack of sufficient co-stimulatory
      molecules. Immune defective DCs provide negative immune signals to CD4+ and CD8+
      T cells. Thereby these T cells are induced to become tolerant to the tumor cells,
      and function as T regulatory/suppressor cells to induce tolerogenic DCs by cell
      cell contact. These DCs tolerized to tumor antigens may further render
      tolerogenicity to many more T cells via intercellular contact, and thus lead to a
      vicious cycle cascade. This model allowed us to envisage modified strategies of
      antitumor chemotherapy. We may use anticancer drugs with higher specificity to
      tumor cells, or in combination with immunopotentiator to disrupt the vicious
      cycle cascade, and expect better clinical result.

PMID- 17555886
TI  - The overall benefits risks and costs of multiple medical interventions may be
      less favourable than the sum of the benefits risks and costs of those individual
      interventions.
AB  - Though clinical trials may give an indication as to the benefits, risks and costs
      of a particular intervention there may be problems applying these data to medical
      practice, which often consists of multiple interventions (simultaneously or
      serially). Mathematical analysis suggests that on account of asymmetries in the
      accumulation of benefits, risks and costs, clinical trials may over-estimate the
      benefit and under-estimate risk and cost of an individual submitting to multiple
      interventions. More sophisticated mathematical modelling may help correct this
      artefact of evidence-based medicine.

PMID- 17555887
TI  - [Breast abscess with Salmonella typhi and review of the literature].
AB  - We report the case of a 54-year-old woman who presented with breast abscess,
      which appeared through a common alimentary toxi-infection with Salmonella Typhi,
      infection, which implied twelve patients having attended the same restaurant.
      With around hundred native cases a year in France, typhoid fever is not a very
      frequent toxi-infection. Among the known extra-intestinal manifestations of
      Salmonella infections, the breast abscess remains rare and the literature
      revealed less than ten published cases, including some revealed the disease. In
      our observation, the imputability of S. Typhi was retained based on the
      chronology of the clinical signs, specific treatments, and the successful outcome
      under antibiotherapy, in spite of the negativity of the breast abscess
      bacteriological samples. We also analyze rare cases of breast abscess due to S.
      Typhi found in the literature.

PMID- 17555888
TI  - [Surgical management of breast microclacifications].
AB  - The breast infraclinic lesions, as microcalcifications, are images found very
      often within the framework of the tracking of the breast cancer. The majority of
      them correspond to benign lesions. The therapeutic strategy of these
      microcalcifications depends on the evaluation of the degree of suspicion of the
      image which classification BI-RADS makes it possible to make more precise and
      more reproducible. In certain cases where a histological diagnosis is necessary,
      the macrobiopsies make it possible to limit the surgery to the only cases where
      the antomo-pathological analysis impose it. Thus, the percutaneous procedure
      performed under local anaesthesia give the possibility of avoiding an useless
      intervention for a benign lesion, or of avoiding, for a malignant lesion, an
      operational time with aiming diagnoses followed by a therapeutic surgical
      recovery. The stereotaxic percutaneous procedures, by confirming a invasive
      malignant lesion, also follow to perform sentinel lymph node biopsy, or to
      program an axillary dissection. It also can in the event of large infraclinic
      lesion, confirmed by two macrobiopsies spaced of more than 3 cm, to perform a
      mastectomy associated to immediate breast surgical reconstruction.

PMID- 17555889
TI  - Neuroglobin and cytoglobin as potential enzyme or substrate.
AB  - The possible enzymatic activities of neuro- and cytoglobin as well as their
      potential function as substrates in enzymatic reactions were studied. Neuro- and
      cytoglobin are found to show no appreciable superoxide dismutase, catalase, and
      peroxidase activities. However, the internal disulfide bond (CD7-D5) of human
      neuroglobin can be reduced by thioredoxin reductase. Furthermore, our in vivo and
      in vitro studies show that Escherichia coli cells contain an enzymatic reducing
      system that keeps the heme iron atom of neuroglobin in the Fe(2+) form in the
      presence of dioxygen despite the high autoxidation rate of the molecule. This
      reducing system needs a low-molecular-weight compound as co-factor. In vitro
      tests show that both NADH and NADPH can play this role. Furthermore, the reducing
      system is not specific for neuroglobin but allows the reduction of the ferric
      forms of other globins such as cytoglobin and myoglobin. A similar reducing
      system is present in eukaryotic tissue protein extracts.

PMID- 17555890
TI  - Different roles of protein dynamics and ligand migration in non-symbiotic
      hemoglobins AHb1 and AHb2 from Arabidopsis thaliana.
AB  - The ligand rebinding kinetics after photolysis of the CO complexes of Arabidopsis
      thaliana hemoglobins AHb1 and AHb2 in solution show very different amplitudes in
      the geminate phase, reflecting different migration pathways of the
      photodissociated ligand in the system of internal cavities accessible from the
      heme. The dependence of the geminate phase on CO concentration, temperature,
      encapsulation in silica gels and presence of glycerol confirms a remarkable
      difference in the internal structure of the two proteins and a dramatically
      different role of protein dynamics in regulating the reactivity with CO. This
      finding strongly supports the idea that they have distinct physiological
      functions.

PMID- 17555891
TI  - Metabolic effects of hemoglobin gene expression in plants.
AB  - Hemoglobin (Hb) genes are ubiquitous in plants. Several classes have been
      identified and are expressed during infection by nitrogen-fixing symbionts, as a
      result of tissue hypoxia, during seed germination, and in developing (e.g.
      meristematic) tissues. The induction of the Hb gene by hypoxia is linked to a
      decrease in ATP levels and is mediated by Ca(2+). Numerous investigations have
      led to the conclusion that the main function of hypoxically-induced Hb is to
      metabolize nitric oxide (NO) formed as a by-product of nitrate/nitrite reduction.
      In this function, Hb serves as a part of an NO dioxygenase system, using traces
      of oxygen to convert NO to nitrate. It operates in conjunction with a
      methemoglobin reductase protein, which reduces the oxidized form of Hb
      (methemoglobin) formed in the course of the NO dioxygenase reaction. The complete
      reaction serves to maintain the cellular energy and redox state. Plant
      hemoglobins may also function to modulate effects of plant hormones that employ
      NO as a downstream signal transduction component.

PMID- 17555892
TI  - The molecular heterogeneity of hemocyanin: its role in the adaptive plasticity of
      Crustacea.
AB  - Crustacean hemocyanin (Hc) represents a unique case of molecular heterogeneity
      among oxygen-carrying proteins. The existence of different genes, encoding single
      polypeptide chains, constitutes the genetic basis for the inter- and intra
      specific polymorphism. In addition, the large number of Hc subunits within
      crustacean species, together with their flexible expression, provides an
      efficient intrinsic mechanism of modulation of oxygen transport. This review
      presents a description and classification of the various aspects of crustacean Hc
      heterogeneity and defines its role in a perspective of crustacean adaptive
      physiology.

PMID- 17555894
TI  - Analysis of Quil A-phospholipid mixtures using drift spectroscopy.
AB  - The aim of this study was to investigate molecular interactions between Quil A
      and phosphatidylcholine in the solid state using diffuse reflectance infrared
      Fourier-transform spectroscopy (DRIFTS). Analysis of the interactions was
      characterized on the different regions of phosphatidylcholine: hydrophobic chain,
      interfacial and headgroup regions. The spectra of the hydrocarbon region of
      phosphatidylcholine alone compared to that for the binary mixture of Quil A and
      phosphatidylcholine were similar. These findings suggest that Quil A did not
      cause conformational disorder of the fatty acyl chains of the phospholipid. In
      contrast, a shift in the wavenumber of the choline group and a broad band in this
      moiety indicate a modification of the phospholipid in the headgroup region due to
      interaction between Quil A and phosphatidylcholine. These results suggest
      possibly ionic interactions between the negatively charged glucuronic acid moiety
      of the Quil A molecule with the positively charged choline group. The findings
      could also be the result of conformational changes in the choline group because
      of the intercalation of sugar moieties in Quil A between the choline and
      phosphate groups due to hydrogen bonding. Shift of wavenumbers to lower values on
      the carbonyl group was observed suggesting hydrogen bonding between Quil A and
      phosphatidylcholine. The difference in degrees of wavenumber shift
      (choline>phosphate>carbonyl group) and observed broad bands indicated that Quil A
      preferentially interacted with phosphatidylcholine on the hydrophilic headgroup.
      Cholesterol influenced such interactions at relatively high concentration (60%,
      w/w).

PMID- 17555893
TI  - Differentiation of xenografted human fetal lung parenchyma.
AB  - The goal of this study was to characterize xenografted human fetal lung tissue
      with respect to developmental stage-specific cytodifferentiation. Human fetal
      lung tissue (pseudoglandular stage) was grafted either beneath the renal capsule
      or the skin of athymic mice (NCr-nu). Tissues were analyzed from 3 to 42 days
      post-engraftment for morphological alterations by light and electron microscopy
      (EM), and for surfactant protein mRNA and protein by reverse transcription
      polymerase chain reaction (RT-PCR) and immunocytochemistry (ICC), respectively.
      The changes observed resemble those seen in human lung development in utero in
      many respects, including the differentiation of epithelium to the saccular stage.
      Each stage occurred over approximately one week in the graft in contrast to the
      eight weeks of normal in utero development. At all time points examined, all four
      surfactant proteins (SP-A, SP-B, SP-C, and SP-D) were detected in the epithelium
      by ICC. Lamellar bodies were first identified by EM in 14 day xenografts. By day
      21, a significant increase in lamellar body expression was observed. Cellular
      proliferation, as marked by PCNA ICC and elastic fiber deposition resembled those
      of canalicular and saccular in utero development. This model in which xenografted
      lung tissue in different stages of development is available may facilitate the
      study of human fetal lung development and the impact of various pharmacological
      agents on this process.

PMID- 17555895
TI  - The characterization of paclitaxel-loaded microspheres manufactured from blends
      of poly(lactic-co-glycolic acid) (PLGA) and low molecular weight diblock
      copolymers.
AB  - Paclitaxel-loaded biodegradable drug delivery systems manufactured from
      poly(lactic-co-glycolic acid) (PLGA) are known to release the drug at extremely
      slow rates. The objective of this study was to characterize paclitaxel-loaded
      microspheres composed of blends of PLGA with low molecular weight ampipathic
      diblock copolymers. The encapsulation and release of a series of poly(epsilon
      caprolactone) (PCL)- or poly(D,L-lactic acid) (PDLLA)-co-methoxypolyethylene
      glycol (MePEG) diblock copolymers was measured using quantitative gel permeation
      chromatography. Polymeric miscibility was determined by glass transition
      temperature measurements using differential scanning calorimetry and paclitaxel
      release was measured using HPLC methods. The PCL- and PDLLA-based diblock
      copolymers encapsulated at high efficiency and were miscible in PLGA microspheres
      (30-120m microm size range). The burst phase of paclitaxel release was increased
      up to 20-fold by the inclusion of diblock copolymers in PLGA microspheres.
      Approximately 10% of the more hydrophobic PCL-based copolymers released from the
      microspheres in a short burst over 3 days followed by very slow release over the
      following 10 weeks. Only the PDLLA-based copolymer released from the PLGA
      microspheres in a controlled manner over 10 weeks. All microspheres containing
      PEG were found to have more hydrophilic surfaces (as measured by contact angle)
      with improved biocompatibility (reduced neutrophil activation) compared to PLGA
      only microspheres. These results indicate that low molecular weight polyester
      based diblock copolymers may be effectively encapsulated in PLGA microspheres to
      increase paclitaxel release (probably through a micellization process) and
      improve biocompatibility.

PMID- 17555896
TI  - Increase in cochlear microphonic potential after toluene administration.
AB  - Human and animal studies have shown that toluene can cause hearing loss. In the
      rat, the outer hair cells are first disrupted by the ototoxicant. Because of
      their particular sensitivity to toluene, the cochlear microphonic potential (CMP)
      was used for monitoring the cochlea activity of anesthetized rats exposed to both
      noise (band noise centered at 4 kHz) and toluene. In the present experiment, the
      conditions were specifically designed to study the toluene effects on CMP and not
      those of its metabolites. To this end, 100-microL injections of a vehicle
      containing different concentrations of solvent were made into the carotid artery
      connected to the tested cochlea. Interestingly, an injection of 116.2-mM toluene
      dramatically increased in the CMP amplitude (approximately 4 dB) in response to
      an 85-dB SPL noise. Moreover, the rise in CMP magnitude was intensity dependent
      at this concentration suggesting that toluene could inhibit the auditory efferent
      system involved in the inner-ear or/and middle-ear acoustic reflexes. Because
      acetylcholine is the neurotransmitter mediated by the auditory efferent bundles,
      injections of antagonists of cholinergic receptors (AchRs) such as atropine, 4
      diphenylacetoxy-N-methylpiperidine-methiodide (mAchR antagonist) and dihydro-beta
      erythroidine (nAchR antagonist) were also tested in this investigation. They all
      provoked rises in CMP having amplitudes as large as those obtained with toluene.
      The results showed for the first time in an in vivo study that toluene mimics the
      effects of AchR antagonists. It is likely that toluene might modify the response
      of protective acoustic reflexes.

PMID- 17555897
TI  - Inhibitive effects of Fructus Psoraleae extract on dopamine transporter and
      noradrenaline transporter.
AB  - A petroleum ether extract (FP) from Fructus Psoraleae, seeds of Psoralea
      corylifolia L. (Leguminosae), was found to strongly inhibit dopamine (DA) uptake
      by dopamine transporter (DAT) heterogeneously expressed cells (D8 cells) and
      noradrenaline (NE) uptake by noradrenaline transporter (NET) heterogeneously
      expressed cells, which, however, had no effect on gamma-aminobutyric acid
      transporter heterogeneously expressed cells and serotonin transporter
      heterogeneously expressed cells at the concentration up to 100 microg/ml. These
      inhibitory effects were also confirmed by experiments on SK-N-SH cell line and
      synaptosomes from rats' brains. In addition, FP showed a significantly mitigating
      effect on 1-methyl-4-pyridinium induced injury of D8 cells. Meanwhile, FP dose
      dependently reduced the binding of tritium-labeled cocaine analog (-)-2beta
      carbomethoxy-3beta-(4-fluorophenyl) tropane to DAT of D8 cells, which suggests
      that FP may inhibit DAT activity in the same way as cocaine does. Behavioral
      study showed FP had a long-lasting stimulant effects on the activity of intact
      mice and reserpinized mice. So FP is proposed as a kind of DAT and NET inhibitor
      and may be involved in the process of regulating the DA and NE system, and FP or
      its unknown bioactive compounds may be developed into new medicines for disorders
      such as Parkinson's disease, depression, Attention Deficit Hyperactivity Disorder
      (ADHD) or cocaine addiction.

PMID- 17555898
TI  - Selective colorimetric determination of TNT partitioned between an alkaline
      solution and a strongly basic Dowex 1-X8 anion exchanger.
AB  - The Meisenheimer anions formed from TNT in KOH solutions in alcohol or acetone
      were used in screening tests for TNT among possible nitro-explosives. The same
      reaction was used for the spectrophotometric assay of TNT in soil by CRREL (Cold
      Regions Research & Engineering Laboratory of the U.S. Army) method, also known as
      Jenkins' method, but the color stability was too dependent on the solution
      composition and the water tolerance was low, necessitating complete drying of
      soil samples (which may cause partial analyte decomposition) prior to analysis.
      This study reports the development of a colorimetric method based on the solid
      phase extraction (SPE) of the Meisenheimer anion formed from TNT and aqueous NaOH
      into a strongly basic anion exchange resin Dowex 1-X8 (OH(-) form). The orange
      red color that developed both in the solid resin and solution phases was
      persistent for at least 1h. The resin was let to swell in alcohol, washed first
      with 1M aqueous NaOH, and then with H(2)O before use. To 5 mL of 4-400 ppm TNT
      solutions in 1:1 (v/v) acetone-water, 0.5 mL of 5% NaOH was added, diluted to 50
      mL with 1:1 acetone-water, and the resulting solutions (containing the orange-red
      Meisenheimer anion of TNT) were agitated at room temperature with 0.9 g resin for
      < or =50 min. TNT exhibited a reasonably constant distribution coefficient
      between the resin and aqueous phases. The absorbance of the filtered solutions
      was measured against a reagent blank at 500nm. The TNT-loaded resins were
      regenerated with 1M HCl containing sodium sulfite. The calibration line of
      filtrate absorbance versus analytical concentration was linear over two orders of
      magnitude between 0.4 and 40 ppm TNT in final solution. Unlike Jenkins' method,
      the method was tolerant to 100-fold (by mass) of common soil anions like sulfate,
      nitrate, and chloride. The basic advantages of the developed colorimetric method
      over the similar CRREL/Jenkins' method may be summarized as color stability,
      water and common ion tolerance, lowering of the LOD, and widening of the linear
      range. As opposed to Jenkins' method, the charge-transfer bands characteristic to
      colorimetric detection were not obscured by the presence of water. The method is
      suitable for on-site applications, because the color developed in heterogenous
      solution was stabilized, and the method can be easily practiced with a portable
      colorimeter to large numbers of samples.

PMID- 17555899
TI  - Long-term stability of various drugs and metabolites in urine, and preventive
      measures against their decomposition with special attention to filtration
      sterilization.
AB  - The long-term stability of drugs and metabolites of forensic interest in urine,
      and preventive measures against their decomposition have been investigated, with
      special attention to filtration sterilization. An aseptic urine collection kit,
      which was recently developed based on filtration sterilization, was utilized for
      the aseptic collection and storage of urine samples. For evaluating preservation
      measures, methamphetamine (MA), amphetamine (AP), nitrazepam (NZ), estazolam
      (EZ), 7-aminoflunitrazepam (7AF), cocaine (COC), and 6-acetylmorphine (6AM) were
      spiked into urine at 500 ng/mL each, and were monitored for 6 months at 25, 4,
      and -20 degrees C, after the addition of NaN(3) and/or filtration sterilization
      using the aseptic collection kit. In severely contaminated urine with bacteria,
      there were significant losses of 7AF and NZ, and slight decomposition of MA and
      AP at 25 degrees C. However, such degradation was successfully suppressed by the
      use of the kit, though the use of the kit and NaN(3) were preferred for 7AF. The
      kit was also effective in preventing the hydrolyses of COC and 6AM, while it was
      suggested that the common preservative NaN(3) can accelerate the hydrolysis of
      such ester-type drugs and metabolites.

PMID- 17555900
TI  - Electroencephalographic changes before the onset of symptomatic West syndrome.
AB  - To clarify the characteristics of the mode of appearance and morphology of
      epileptiform discharges before the onset of West syndrome (WS). The subjects were
      25 infants whose electroencephalograms (EEGs) were recorded before the onset of
      WS and whose first EEG was recorded before 6 months of corrected age (CA). We
      extensively analyzed the chronological and topographical changes of the
      epileptiform discharges before the onset of WS. The location of the initial
      epileptiform discharges was in the posterior areas in 14 (Group O), the multiple
      areas in 7 (Group M), and areas other than occipital in 4 (Group non-O). Twelve
      of the 14 patients in Group O were premature infants, and all but one had PVL.
      Most patients in Group M were full-term infants or near full-term infants who had
      hypoxic damage. The ages at the appearance of the initial epileptiform discharges
      in Group O were significantly later than those in Group M: 3.0-5.9 months of CA
      in Group O vs. -0.1 to 2.0 months of CA in Group M. These facts suggest that the
      difference of brain damage is related to both the topographical characteristics
      and the age at the appearance of initial epileptiform discharges, and around 3
      months of CA is a critical period for the appearance of occipital
      hyperexcitability. Hypsarrhythmia and tonic spasms appeared almost simultaneously
      from 4 to 6 months of CA in most patients. To predict the occurrence of WS in
      high-risk infants, EEG follow-ups from early infancy are very useful.

PMID- 17555901
TI  - Focal liver lesions: whether a standard dose (0.05 mmol/kg) gadobenate
      dimeglumine can provide the same diagnostic data as the 0.1 mmol/kg dose.
AB  - OBJECTIVE: Gadobenate dimeglumine (Gd-BOPTA) is a liver-specific contrast agent
      also showing a distribution in the extracellular compartment which is recommended
      to be used at standard dose (0.05 mmol/kg) in magnetic resonance imaging (MRI) of
      liver lesions. However, its use at 0. 1mmol/kg is gradually increasing in recent
      clinical practice. Which dose should we use in routine MRI of liver lesions from
      now on? This study investigated the efficacy of Gd-BOPTA at a standard dose
      versus 0.1 mmol/kg dose in demonstrating diagnostic data in MRI of focal liver
      lesions. MATERIALS AND METHODS: The study included 47 patients with focal liver
      lesions. Twenty-two patients received standard dose and 25 patients received 0.1
      mmol/kg dose Gd-BOPTA intravenously. MRI of both groups was carried out with T1-A
      FLASH-2D and T2-A TURBO spin echo before contrast injection and T1-A FLASH-2D
      sequences in dynamic and late phase (90th minute) after the contrast injection.
      The lesion conspicuity for each image was evaluated qualitatively. Liver signal
      to noise ratio (SNR), absolute lesion-liver contrast to noise ratio (CNR), mean
      lesion-liver CNR and contrast enhancement rate of the liver obtained from both
      groups were compared quantitatively. RESULTS: While liver contrast enhancement
      rate in the group receiving standard dose Gd-BOPTA were 41%+/-42 in the arterial
      phase, 66%+/-58 in the portal phase, 45%+/-45 in the venous phase and 42%+/-88 in
      the late phase, these values were 43%+/-59, 86%+/-73, 63%+/-75 and 61%+/-105,
      respectively, in the group receiving the dose of 0.1 mmol/kg. There were no
      statistically significant differences between the means of both groups. While the
      absolute lesion-liver CNR values were 18+/-15 precontrast, 22+/-18 in the
      arterial phase, 19+/-17 in the portal phase, 15+/-10 in the venous phase and 24+/
      26 in the late phase in the group receiving the standard dose Gd-BOPTA, these
      values were 13+/-11, 18+/-15, 15+/-15, 13+/-13 and 19+/-21, respectively, in the
      group receiving the 0.1 mmol/kg dose. There were no statistically significant
      differences between the means of both groups (p>0.05). However, when the mean
      lesion-liver CNR values were compared, there was statistically significant
      difference between each arterial and portal phases of metastases in both groups
      (p<0.05). There was no statistical difference found in other lesions. When lesion
      conspicuity scores were compared, there were no significant differences between
      the two groups. CONCLUSION: In liver lesions, similar diagnostic data are
      obtained in dynamic and late phase MRI with either standard dose Gd-BOPTA or with
      a dose of 0.1 mmol/kg. Because there was a difference in only metastases in both
      groups, in oncological patients who are being investigated for liver metastasis,
      it is expedient to use a dose of 0.1 mmol/kg.

PMID- 17555902
TI  - Combined stent placement and high dose PGE1 drip infusion for chronic occlusion
      of the superficial femoral artery as a modality to salvage chronic critical limb
      ischemia.
AB  - PURPOSE: To assess the initial effect, short-term patency, and limb salvage rates
      of combined stent placement and high-dose prostaglandin E-1 (PGE1) drip infusion
      for chronic occlusion of the superficial femoral artery (SFA). MATERIALS AND
      METHODS: A total of 15 arteriosclerotic occlusive lesions of the SFA were treated
      in 11 consecutive patients (mean age: 78.4 years old). All cases were of category
      4 or 5, based on the criteria of the Society of Vascular Surgery and Intermittent
      Society for Cardiovascular Surgery (SVC/ISCVS). In all cases a self-expandable
      stainless steel stent was implanted. PGE1 treatment was started 3-5 days before
      stent placement and continued for 7-10 days after the intervention. The technical
      success, limb salvage outcomes, patency rates, and complications were examined.
      RESULTS: In all cases, the technical success rate of the procedure was 100%.
      After stent implantation, the clinical status of all cases was improved by at
      least +2, and major amputation was not required in any cases. The 12-month
      primary, secondary patency rates, and limb salvage rate were 57%, 100%, and 100%,
      respectively. CONCLUSION: Combined stent placement and high-dose PGE1 drip
      infusion is a treatment of choice for salvaging the lower limb of a patient with
      chronic critical ischemia.

PMID- 17555903
TI  - Diffusion weighted MR imaging in non-infarct lesions of the brain.
AB  - Diffusion weighted imaging (DWI) is a relatively new method in which the images
      are formed by the contrast produced by the random microscopic motion of water
      molecules in different tissues. Although DWI has been tried for different organ
      systems, it has been found its primary use in the central nervous system. The
      most widely used clinical application is in the detection of hyperacute infarcts
      and the differentiation of acute or subacute infarction from chronic infarction.
      Recently DWI has been applied to various other cerebral diseases. In this
      pictorial paper the authors demonstrated different DWI patterns of non-infarct
      lesions of the brain which are hyperintense in the diffusion trace image, such as
      infectious, neoplastic and demyelinating diseases, encephalopathies - including
      hypoxic-ischemic, hypertensive, eclamptic, toxic, metabolic and mitochondrial
      encephalopathies - leukodystrophies, vasculitis and vasculopathies, hemorrhage
      and trauma.

PMID- 17555904
TI  - Hip osteoarthritis: what the radiologist wants to know.
AB  - Osteoarthritis (OA) is the most common disease of the hip joint seen in adults.
      The diagnosis of OA is based on a combination of radiographic findings of joint
      degeneration and characteristic subjective symptoms. The lack of a radiographic
      consensus definition has resulted in a variation of the published incidences and
      prevalence of OA. The chronological sequence of degeneration includes the
      following plain radiographic findings: joint space narrowing, development of
      osteophytes, subchondral sclerosis, and cyst formation. There are cases though,
      that plain radiographs show minor changes and the clinical suspicion of early
      disease can be confirmed with more sophisticated imaging methods, such as multi
      detector computed tomography and MR imaging. The present article will review all
      the clinical information on the hip OA together with an updated radiological
      approach, with emphasis on the early depiction and the differential diagnosis of
      the disease.

PMID- 17555905
TI  - The role of MR imaging in staging femoral head osteonecrosis.
AB  - Reliability, accuracy and prognostic value of any classification system are
      important in evaluation and treatment of femoral head osteonecrosis. The purpose
      of the present study was to correlate the plain radiographs with MRI in femoral
      head osteonecrosis. Between 2000 and 2005, 115 hips (72 patients) were evaluated
      and classified according to the ARCO classification criteria with the use of
      plain radiographs and additional application of MRI. Classification was performed
      by consensus between a musculoskeletal radiologist and an orthopaedic surgeon.
      Sensitivity (SEN), specificity (SP), positive (PPV) and negative (NPV) predictive
      value of X-rays were estimated. According to MRI, 17 hips were classified as
      stage I, 25 as stage II, 48 as stage III and 25 as stage IV. The SEN, SP, PPV and
      NPV of plain radiographs were for stage II 88%, 90.5%, 78.6% and 95%; for stage
      III 79.2% 82%, 80.8% and 87.2%; for stage IV 76%, 100%, 100% and 90.9%,
      respectively. The agreement between plain radiographs and MRI was 80.6% for
      staging the disease, 71.2% for recording the location of the osteonecrotic
      lesion, 67.1% for evaluating the size of the lesion, 79.2% for the presence of
      collapse of the articular surface and 56.3% for the degree of collapse. In
      conclusion, the ARCO classification could miss important information in stages II
      and III, where treatment aims at preservation of the hip joint integrity. The
      results of the present study suggest that MRI should be incorporated in the
      classification of osteonecrosis (stages II and III), to add accuracy and
      prognostic value.

PMID- 17555906
TI  - Osteonecrosis of the femoral head: etiology, imaging and treatment.
AB  - Osteonecrosis of the femoral head is a disabling clinical entity affecting young
      adults that usually leads to destruction of the hip joint. A high index of
      suspicion is necessary for the diagnosis due to the insidious onset of the bone
      infarcts and the lack of specific clinical signs at the early stages. Many
      etiology-associated factors have been identified reducing thus the number of
      idiopathic cases. A number of joint salvaging treatment options are available if
      early diagnosis can be achieved. MR imaging has been proved to be a highly
      accurate method both for early diagnosis and for staging of the disease.
      Replacement of the hip joint is the last resort for pain relief and function,
      although non-desirable because of the young age of the affected population.

PMID- 17555907
TI  - Femoral head osteonecrosis: volumetric MRI assessment and outcome.
AB  - Effective treatment of femoral head osteonecrosis (FHON) requires early diagnosis
      and accurate assessment of the disease severity. The ability to predict in the
      early stages the risk of collapse is important for selecting a joint salvage
      procedure. The aim of the present study was to evaluate the outcome in patients
      treated with vascularized fibular grafts in relation to preoperative MR imaging
      volumetry. We studied 58 patients (87 hips) with FHON. A semi-automated octant
      based lesion measurement method, previously described, was performed on the T1-w
      MR images. The mean time of postoperative follow-up was 7.8 years. Sixty-three
      hips were successful and 24 failed and converted to total hip arthroplasty within
      a period of 2-4 years after the initial operation. The rate of failures for hips
      of male patients was higher than in female patients. The mean lesion size was 28%
      of the sphere equivalent of the femoral head, 24+/-12% for the successful hips
      and 37+/-9% for the failed (p<0.001). The most affected octants were antero
      supero-medial (58+/-26%) and postero-supero-medial (54+/-31%). All but postero
      infero-medial and postero-infero-lateral octants, showed statistically
      significant differences in the lesion size between patients with successful and
      failed hips. In conclusion, the volumetric analysis of preoperative MRI provides
      useful information with regard to a successful outcome in patients treated with
      vascularized fibular grafts.

PMID- 17555909
TI  - Simultaneous determination of three aconitum alkaloids in urine by LC-MS-MS.
AB  - A sensitive method has been developed for the identification and quantification
      of the toxic alkaloids yunaconitine, crassicauline A, and foresaconitine in urine
      specimens. After solid-phase extraction using Oasis MCX cartridges, the extracts
      were analyzed by LC-MS-MS. The limit of detection is 0.03 ng/mL urine for
      yunaconitine and 0.05 ng/mL urine for crassicauline A and foresaconitine; the
      limit of quantitation is 0.15 ng/mL urine for yunaconitine and 0.20 ng/mL urine
      for crassicauline A and foresaconitine. The method was employed in the analysis
      of the urine of a 55-year-old male who died after ingestion of herbal medicine
      powder made from the roots of aconite. Yunaconitine, crassicauline A and
      foresaconitine were identified in the urine. Crassicauline A and foresaconitine
      were thus identified in a biological specimen for the first time.

PMID- 17555910
TI  - Neck management in medullary thyroid carcinoma.
AB  - AIMS: The aims of this study were to retrospectively evaluate incidence and
      patterns of lymph node metastases, surgical treatment and prognostic factors of
      medullary thyroid carcinoma. METHODS: Out of a group of 70 MTC patients data of
      67 patients were collected. Sixty-two of these patients underwent surgery. Apart
      from thyroidectomy, 16 patients underwent a bilateral neck dissection, 21 a
      unilateral neck dissection and 29 a paratracheal dissection or node-picking
      operation. Thirty-six patients were irradiated, of which 31 postoperatively and
      five with palliative intent. RESULTS: Lymph node metastases were found in 91% of
      the ipsilateral neck dissection specimens, 91% of the paratracheal dissections
      and 63% of the contralateral dissections. Of the 12 elective neck dissections, 5
      were tumor positive. Level VI was positive in 91% of the cases where a dissection
      was done, whereas preoperatively only 16% were scored tumor positive. During
      follow-up 22 of the 67 patients developed one or more locoregional recurrences
      (in total 28 recurrences). The most important factors that were correlated with a
      worse prognosis of survival were late stage of disease (stage III and IV)
      (p=0.0014), high number of positive lymph nodes (p=0.0023) and incomplete
      surgical resection (p=0.0002). CONCLUSIONS: The high rate of locoregional
      recurrences in this study are a strong argument for a more aggressive approach to
      the primary and neck. A routine central and ipsilateral selective neck dissection
      of levels II-V should be considered in all MTC patients based on the high
      incidence of metastases and the relative low morbidity of a unilateral neck
      dissection. Patients referred after thyroidectomy alone with elevated
      (stimulated) calcitonin levels should be re-operated, performing an elective or
      therapeutic central and unilateral neck dissection.

PMID- 17555911
TI  - Stage of breast cancers found during the surveillance of women with a familial or
      hereditary risk.
AB  - AIM: To compare the breast cancer stages found during MG alone surveillance in
      women at increased risk with those detected in a program where MRI was added.
      METHODS: Stage results of in a retrospective MG alone study of prospectively
      followed patients, compared with the pooled stage results of breast cancers
      MG/MRI surveillance. RESULTS: One hundred and-fifty-one patients were detected
      with a first or contralateral breast cancer. Interval cancers were diagnosed in
      56% of the BRCA1, 42% of the BRCA2 and 28% of the non-BRCA carriers. A
      considerable proportion of the breast cancers were detected with breast self
      examination alone: 41%, 27% and 31% respectively. Nevertheless the established
      goals for biennial population screening were reached, except for the BRCA2
      carriers, but this group was small. Comparison with pooled data from published
      MG/MRI surveillance studies did not show significant differences in the stages,
      except for the BRCA2 carriers. CONCLUSION: Breast cancers detected in a MG alone
      surveillance program for women at increased risk fulfill most goals set for
      population screening except for the BRCA2 carriers. Breast self-examination
      appears to be a valuable additional detection method especially for BRCA1
      carriers, who are at risk of developing a highly proliferating breast cancer.

PMID- 17555912
TI  - Synthesis and in vitro cytotoxicity evaluation of 4-aminoquinoline derivatives.
AB  - A series of 4-aminoquinoline derivatives were synthesized by the reaction of 4
      chloro-7-substituted-quinolines with the corresponding mono/dialkyl amines. The
      structures of the synthesized compounds were confirmed by NMR and FAB-MS spectral
      and elemental analyses. Subsequently, the compounds were examined for their
      cytotoxic effects on two different human breast tumor cell lines: MCF7 and MDA
      MB468. Although all compounds examined were quite effective on both cell lines,
      the compound N'-(7-chloro-quinolin-4-yl)-N,N-dimethyl-ethane-1,2-diamine emerged
      as the most active compound of the series. It was particularly potent against MDA
      MB 468 cells when compared to chloroquine and amodiaquine. The compound butyl-(7
      fluoro-quinolin-4-yl)-amine showed more potent effects on MCF-7 cells when
      compared to chloroquine. Therefore, 4-aminoquinoline can serve as the prototype
      molecule for further development of a new class of anticancer agents.

PMID- 17555913
TI  - Pulmonary manifestations of Pyoderma gangrenosum.
AB  - INTRODUCTION: Pyoderma gangrenosum is an uncommon ulcerative cutaneous disorder.
      Extracutaneous localizations are rare. Respiratory system involvement has been
      described in a few cases, but the pulmonary features reported were highly
      variable. CASE: We report two cases of patients with Pyoderma gangrenosum
      combining cutaneous and pulmonary manifestations. One case presented multiple
      nodular lesions, some with cavitation. The underlying disease was varicella
      zoster virus infection. The second presented pneumonitis with bronchiolar
      micronodules. DISCUSSION: Few cases have reported Pyoderma gangrenosum with
      pulmonary involvement, which appears to be manifested mainly as nodules or
      interstitial lung disease. The principal differential diagnosis is Wegener's
      granulomatosis.

PMID- 17555914
TI  - [Prophylactic treatment for recurrent major depression].
AB  - Approximately 80% of the patients who have a first episode of major depression
      will have at least one more. The lifetime average is 4 episodes. Nevertheless,
      despite this high risk of relapse, often severe and disabling, only half the
      patients with recurrent major depression receive prophylactic treatment. Long
      term antidepressant treatment appears to be the most effective option for
      prophylactic treatment of recurrent major depression. The optimal duration of
      this treatment remains uncertain, in part because of the lack of long-term
      studies, that is, with a follow-up longer than 2 years. The interpretation of
      some of the controlled studies of the prophylactic efficacy of antidepressant
      treatment is limited by methodological issues: most antidepressants have not been
      studied in a purely prophylactic approach, but rather as a maintenance treatment
      after response during an acute episode. Lithium and carbamazepine may be
      prescribed as second-line preventive treatment. Although we lack controlled
      studies of the prophylactic efficacy of psychotherapies in recurrent depression,
      interpersonal, cognitive and behavioral psychotherapies have been shown to be
      effective in reducing the relapse rate, especially when associated with
      antidepressants. Treatment duration should be determined individually, taking
      into account the patient's risk profile and international and national
      guidelines.

PMID- 17555915
TI  - [Frontotemporal dementia].
AB  - Frontotemporal dementia usually begins before the age of 65 years. It is
      manifested by behavioral and language disorders. The lesions observed in
      frontotemporal dementia affect the frontal and temporal lobes bilaterally. One
      third of patients have a psychiatric diagnosis at the onset of disease. The
      genetic component is important: 30-50% of patients have a family history of this
      disease. Cholinergic effects are not associated with frontotemporal dementia and
      therefore anticholinesterase treatment is not indicated.

PMID- 17555916
TI  - [MRI of prostate cancer].
AB  - Endorectal MRI, now a fast and reliable examination, is an essential part of the
      local work-up for prostate cancer, regardless of the treatment envisioned. MRI
      spectroscopy, an actively maturing technique, makes it possible to combine
      anatomical and metabolic information that can be used for detection, staging, and
      posttreatment follow-up of prostate cancer. In patients with repeated negative
      biopsies, spectroscopy and dynamic gadolinium injection will be able to detect
      atypical cancer sites that escape routine biopsies. MRI of lymph nodes with
      ultrasmall superparamagnetic iron oxide (USPIO) injection will improve diagnostic
      performance in the detection of lymph node metastases. In the planning of
      conservative treatment, MRI and especially spectroscopic MRI will increasingly
      replace computed tomography. Finally, endorectal MRI of the prostate,
      spectroscopy, and dynamic injection will show local recurrences.

PMID- 17555917
TI  - [Syringomyelia].

PMID- 17555918
TI  - Pleural effusion aspiration in a small hospice setting.

PMID- 17555919
TI  - The effects of a two-week trial of transcutaneous electrical nerve stimulation
      for pediatric chronic back pain.

PMID- 17555920
TI  - Oxygen use--patients define symptomatic benefit discerningly.

PMID- 17555921
TI  - Withdrawal acute psychosis after corticosteroid discontinuation.

PMID- 17555922
TI  - Racial differences in the growth of noncancer diagnoses among hospice enrollees.
AB  - Patients with noncancer life-limiting illnesses now represent over half of all
      hospice enrollees, compared to only one-quarter of enrollees in 1992. Whether
      this growth in enrollees with noncancer diagnoses has been similar for Caucasians
      and African Americans, a group historically underrepresented in hospice, has not
      been described. The purpose of this study was to compare rates of noncancer
      diagnoses among African American and Caucasian hospice enrollees. We analyzed
      data from the administrative database of VITAS Healthcare Corporation, including
      all African Americans and Caucasians discharged from hospice between January 1,
      1999 and December 31, 2003. Of the 166,390 eligible discharges, 14.6% were
      African American, and 85.4% were Caucasian. Over the five-year study period,
      there was a similar increase in the crude proportion of enrollees with noncancer
      diagnoses in both groups, from 42% to 49.7% among African Americans and 57.9% to
      64.3% among Caucasians. However, in multivariate analysis (adjusted for age,
      gender, admission level of care, payment source, Health Maintenance Organization
      (HMO) use, discharge year, and hospice program characteristics-size, location,
      presence of an inpatient unit), African Americans had 32% lower odds of having a
      noncancer (vs. cancer) diagnosis than Caucasians (odds ratio [OR] 0.68 [0.66,
      0.77]). While numerous studies document lower rates of hospice use among African
      Americans than Caucasians, these findings suggest disease-specific differences in
      patterns of hospice use, with greater disparities in hospice use among African
      Americans with noncancer diagnoses than those with cancer diagnoses. Targeted
      efforts to increase hospice use among African Americans with noncancer diagnoses
      may be important in reducing racial disparities in overall hospice use and
      improving the quality of care for dying African Americans.

PMID- 17555924
TI  - Not all systolic velocities indicate obstruction in hypertrophic cardiomyopathy:
      a simultaneous Doppler catheterization study.

PMID- 17555923
TI  - Nanoparticle effects on rat alveolar epithelial cell monolayer barrier
      properties.
AB  - Inhaled nanoparticles have been reported to contribute to deleterious effects on
      human health. In this study, we investigated the effects of ultrafine ambient
      particulate suspensions (UAPS), polystyrene nanoparticles (PNP; positively and
      negatively charged; 20, 100, 120 nm), quantum dots (QD; positively and negatively
      charged; 30 nm) and single-wall carbon nanotubes (SWCNT) on alveolar epithelial
      cell barrier properties. Transmonolayer resistance (R(t)) and equivalent short
      circuit current (I(eq)) of primary rat alveolar epithelial monolayers were
      measured in the presence and absence of varying concentrations of apical
      nanoparticles. In some experiments, apical-to-basolateral fluxes of radiolabeled
      mannitol or inulin were determined with or without apical UAPS exposure and
      lactate dehydrogenase (LDH) release was analyzed after UAPS or SWCNT exposure.
      Results revealed that exposure to UAPS decreased R(t) and I(eq) significantly
      over 24 h, although neither mannitol nor inulin fluxes changed. Positively
      charged QD decreased R(t) significantly (with subsequent recovery), while
      negatively charged QD did not. R(t) decreased significantly after SWCNT exposure
      (with subsequent recovery). On the other hand, PNP exposure had no effects on
      R(t) or I(eq). No significant increases in LDH release were observed after UAPS
      or SWCNT exposure. These data indicate that disruption of alveolar epithelial
      barrier properties due to apical nanoparticle exposure likely involves alteration
      of cellular transport pathways and is dependent on specific nanoparticle
      composition, shape and/or surface charge.

PMID- 17555925
TI  - Left valsalva sinus aneurysm rupture into left atrium and aortic valve prolapse
      confirmed with transesophageal echocardiography.
AB  - We report a very rare case of left Valsalva sinus aneurysm rupture into left
      atrium in a 55-year-old man with severe aortic regurgitation caused by aortic
      valve prolapse. The Valsalva sinus aneurysm rupture was clearly visualized with
      transesophageal echocardiography performed to further delineate the aortic valve
      pathology. The 3-dimensional reconstruction of multislice computed tomography
      images nicely visualized the left Valsalva sinus aneurysm.

PMID- 17555926
TI  - Global left ventricular systolic function based on the sum of regional myocardial
      velocities during exercise echocardiography.
AB  - OBJECTIVES: We sought to assess the relationship between global Doppler
      myocardial imaging (DMI) and left ventricular (LV) ejection fraction (LVEF) at
      both rest and exercise. BACKGROUND: We have previously demonstrated that global
      DMI correlates with LVEF at rest with low variability. METHODS: LVEF by 2
      dimensional echocardiography, systolic global tissue Doppler velocity (s-TDV),
      strain (S) rate (SR), and S were assessed in 122 patients. LVEF was measured at
      rest and at peak exercise, whereas DMI was performed at rest and immediately
      postexercise. The region of interest by color DMI was set to enclose the external
      myocardial border when the LV achieved its maximal dimension. The means of the
      DMI assessments in the 4- and 2-chamber apical views at rest and postexercise
      were measured to correlate with LVEF. RESULTS: Significant correlations were
      found between the LVEF and global s-TDV, SR, and S either at rest (r = 0.32, r =
      0.50, and r = 0.33, all P < .001) or at exercise (r = 0.47, r = 0.63, and r =
      0.40, all P < .001). The best differentiation of an abnormal from a normal LVEF
      (>or=50%) at rest was provided by s-TDV less than 1.8 cm/s (sensitivity 63%,
      specificity 78%, area under the curve [AUC] 0.76, confidence interval [CI] 0.63
      0.90), SR greater than -0.50/s (sensitivity 90%, specificity 76%, AUC 0.86, CI
      0.76-0.97), and S greater than -9% (sensitivity 83%, specificity 75%, AUC 0.81,
      CI 0.70-0.91); whereas at exercise it was provided by s-TDV less than 3.5 cm/s
      (sensitivity 75%, specificity 74%, AUC 0.79, CI 0.69-0.89), SR greater than 
      0.80/s (sensitivity 83%, specificity 81%, AUC 0.91, CI 0.86-0.96), and S greater
      than -11% (sensitivity 67%, specificity 69%, AUC 0.74, CI 0.63-0.85).
      CONCLUSIONS: Global DMI is a valuable tool to assess global LV function during
      exercise.

PMID- 17555927
TI  - Comparison of novel echocardiographic parameters of right ventricular function
      with ejection fraction by cardiac magnetic resonance.
AB  - BACKGROUND: Assessment of right ventricular (RV) function by echocardiography is
      challenging. Newer techniques such as tissue Doppler echocardiography and strain
      echocardiography may allow accurate and quantitative assessment of RV function.
      We sought to determine which echocardiographic variable or variables best
      correlated with RV ejection fraction (RVEF) by cardiac magnetic resonance.
      METHODS: We performed conventional echocardiography, tissue Doppler
      echocardiography, strain echocardiography, and cardiac magnetic resonance on 53
      individuals, of which 10 patients had arrhythmogenic RV dysplasia without
      pulmonary hypertension, and 43 were control subjects. RV fractional area change
      (FAC), Tei index, isovolumic acceleration, peak systolic velocity (S'), tissue
      displacement, systolic strain (Ss) rate, and Ss were measured. RESULTS: RVEF,
      FAC, S', tissue displacement, isovolumic acceleration, Ss rate, and Ss were
      significantly lower in patients compared with control subjects (P < or = .05 in
      all) but not the Tei index (P = .07). Regression analysis revealed a significant
      correlation between S', tissue displacement, Ss rate, Ss, and FAC with RVEF (P <
      .05 for all) but not with isovolumic acceleration and Tei index (P = .13 and .39,
      respectively). Multivariate analysis demonstrated a persistent significant
      relationship between S' and FAC with RVEF (both P < .05). However, feasibility,
      and intraobserver and interobserver agreement, were substantially lower for FAC.
      A cut-off value of 8.8 cm/s for S' had sensitivity and specificity of 80% and 79%
      (area under the curve 0.87, P = .01), respectively, for prediction of RVEF less
      than 45%. CONCLUSION: Tissue Doppler echocardiographically derived S' best
      correlates with cardiac magnetic resonance-derived RVEF with high reproducibility
      and may facilitate simple and quantitative assessment of RV function.

PMID- 17555928
TI  - Noninvasive estimation of right ventricular filling pressure by ratio of early
      tricuspid inflow to annular diastolic velocity in patients with and without
      recent cardiac surgery.
AB  - BACKGROUND: Few data are available on the evaluation of right ventricular (RV)
      diastolic function and filling pressures by echocardiography. We aimed to
      determine whether the ratio of early tricuspid inflow to annular diastolic
      velocity (E/E') could be used to estimate RV filling pressure in patients with
      and without recent cardiac surgery. METHODS: In all, 101 data sets including
      invasive and echocardiographic measurements (42 after recent cardiac surgery)
      were simultaneously obtained from patients in the intensive care department.
      Tissue Doppler measurements were performed from the tricuspid annulus. E/E' was
      related to catheter right atrial pressure (RAP) measurements. RESULTS: E/E'
      correlated only moderately with RAP early after cardiac surgery (r = .41, P =
      .007), whereas E/E' correlated strongly with RAP in patients without cardiac
      surgery (r = .83, P < .0001). The sensitivity and specificity of E/E' 4 or
      greater were 88% and 85% for RAP 10 mm Hg or greater in patients who were not in
      the postcardiac surgery status (receiver operating characteristic area 0.93 [95%
      confidence interval: 0.86-0.99]) but 44% and 73% early after cardiac surgery
      (receiver operating characteristic area 0.56 [95% confidence interval: 0.37
      0.75]). E/E' correlated more strongly with RAP when the RV systolic function was
      impaired. In repeated measurements from 12 patients, an increase of greater than
      2 in E/E' was associated with an increase of 5 mm Hg or more in the RAP with a
      sensitivity of 67% and a specificity of 89%. CONCLUSIONS: E/E' is useful for
      noninvasive estimation of RV filling pressure and to detect serial changes in a
      wide range of clinical conditions but is a weak correlate of RAP early after
      cardiac surgery and in patients with normal RV function.

PMID- 17555929
TI  - Does left atrial appendage peak emptying flow velocity predict the electrical
      energy required to achieve successful direct-current cardioversion in patients
      with persistent atrial fibrillation?
AB  - BACKGROUND: The relation of left atrial (LA) appendage peak emptying flow
      velocity (LAAEV) with energy requirement for successful direct-current
      cardioversion (DCCV) in persistent atrial fibrillation (AF) is unknown. LAAEV
      correlates with success of cardioversion of AF to sinus rhythm, both of which are
      related to the LA size and the chronicity of AF. We tested the hypothesis that
      LAAEV can predict optimal energy required for DCCV in persistent AF (>48 hours).
      METHODS: We studied 1050 consecutive patients with persistent AF who underwent
      successful transesophageal echocardiographically guided DCCV from 2000 to 2005.
      After excluding patients with atrial flutter and those receiving antiarrhythmic
      drugs, 454 patients qualified for the study. RESULTS: LAAEV did not correlate
      with cardioversion energy (r = 0.06, P = .23) or number of shocks required for
      successful DCCV (r = 0.05, P = .33). The only predictor of energy required for
      successful cardioversion was the chronicity of AF. CONCLUSION: LAAEV does not
      predict electrical energy required for successful cardioversion in persistent AF.

PMID- 17555930
TI  - The evaluation of real-time 3-dimensional transthoracic echocardiography for the
      preoperative functional assessment of patients with mitral valve prolapse: a
      comparison with 2-dimensional transesophageal echocardiography.
AB  - OBJECTIVE: We sought to compare the feasibility and accuracy of transthoracic
      real-time 3-dimensional echocardiography (RT-3DE) with transesophageal
      echocardiography (TEE) for the preoperative functional assessment of patients
      with mitral valve prolapse. METHODS: In 44 patients with severe mitral
      regurgitation caused by type 2 valve dysfunction, TEE and RT-3DE were performed
      24 hours before surgery and analyzed by two separate observers. TEE and RT-3DE
      images were acquired digitally and stored for offline analysis. The
      echocardiographic results were validated intraoperatively. RESULTS: Five patients
      did not have image quality suitable for analysis with RT-3DE and were excluded
      from analysis, leaving a sample size of 39. In total, 54 of 334 analyzed mitral
      valve segments were diseased. Prolapse of a single mitral valve segment was
      present in 25 patients and 14 patients had complex disease involving two or more
      segments. Sensitivity, specificity, and accuracy for TEE in identification of
      diseased segments were 94%, 100%, and 96%, respectively. The same values for RT
      3DE were 91%, 100%, and 94%, respectively. The differences were not statistically
      significant. Accuracies were not significantly different according to segment
      location. Interobserver agreement was 92% for TEE and 88% for RT-3DE (P =
      nonsignificant). CONCLUSIONS: RT-3DE is feasible with comparative accuracy to TEE
      for precise anatomic localization of prolapsing mitral valve segments. However,
      the technique is limited by poor image quality in 11% of patients.

PMID- 17555931
TI  - Measurement of volumetric flow by real-time 3-dimensional doppler
      echocardiography in children.
AB  - BACKGROUND: We sought to assess the accuracy and reproducibility of an automated
      real-time (RT) 3-dimensional (3D) Doppler echocardiography (RT3DDE) technique for
      measuring volumetric flow (VF) in children. METHODS: A total of 19 healthy
      children (age = 11.5 +/- 3.5 years) were studied to measure VF through mitral
      valve (MV), aortic valve (AV), pulmonary valve (PV), and tricuspid valve (TV) by
      RT3DDE. RT 3D echocardiography was also performed to measure left ventricular
      (LV) end-systolic volume, LV end-diastolic volume, and stroke volume (stroke
      volume = LV end-diastolic volume--LV end-systolic volume), which served as a
      reference standard for comparison with VF by RT3DDE. RESULTS: Compared with
      stroke volume by RT 3D echocardiography, the correlation with VF was excellent
      for MV (r = 0.91), good for AV (r = 0.89) and PV (r = 0.89), but poor for TV (r =
      0.20) by RT3DDE. There were good agreements for AV (bias = 0.9 +/- 5.0 mL), PV
      (bias = -0.4 +/- 5.7 mL), and MV (bias = 4.1 +/- 4.7 mL), and marked
      underestimation for TV (bias = -24.4 +/- 14.6 mL). CONCLUSIONS: Our data
      demonstrated that VF measurement by RT3DDE is feasible and reasonably accurate
      for MV, AV, and PV but problematic for TV.

PMID- 17555932
TI  - Clinical outcome and echocardiographic predictors of aortic valve replacement in
      patients with bicuspid aortic valve.
AB  - BACKGROUND: Clinical outcomes and echocardiographic parameters associated with
      aortic valve replacement (AVR) for bicuspid aortic valve are scarce. METHODS: We
      conducted retrospective analysis of 208 adults with bicuspid aortic valve
      referred for transthoracic echocardiograms. RESULTS: The Kaplan-Meier survival
      free of death or need for cardiac surgery was 72% at 5 years. Cardiac surgery was
      performed in 19%, the majority (68%) for symptomatic aortic stenosis. Peak
      gradient 80 mm Hg or greater (hazard ratio 11.8, 95% confidence interval 3.7
      37.8, P < .0001) and aortic valve area less than or equal to 0.75 cm(2) (hazard
      ratio 2.9, 95% confidence interval 1.0-8.5, P = .05) predicted the need for AVR.
      Patients with a large (54%) versus normal left ventricular outflow tract
      dimension underwent AVR for symptomatic aortic stenosis at a larger calculated
      aortic valve area (1.07 +/- 0.21 vs 0.75 +/- 0.18 cm(2), P < .0001) but at a
      similar peak gradient and velocity ratio (76 +/- 19 vs 76 +/- 22 mm Hg, P = not
      significant; 0.23 +/- 0.06 vs 0.26 +/- 0.12, P = not significant, respectively).
      CONCLUSIONS: Clinical events are common among patients with bicuspid aortic
      valve. Peak gradient 80 mm Hg or more and aortic valve area less than or equal to
      0.75 cm(2) predicts the need for AVR. Gradients and velocity ratio better reflect
      the hemodynamic burden of aortic stenosis in patients with a large left
      ventricular outflow tract.

PMID- 17555933
TI  - Three-dimensional echocardiographic evaluation of right ventricular volume and
      function in pediatric patients: validation of the technique.
AB  - The right ventricle (RV) is the main ventricular chamber in many congenital heart
      diseases before and after surgical correction, and it is the most important
      determinant of outcome in postoperative tetralogy of Fallot and other complex
      malformations. Unfortunately its irregular crescentic shape does not allow the
      use of the geometric assumption used for the left ventricle. Many methods have
      been suggested in the literature to overcome this problem, none fully reliable.
      The introduction of volume-rendered 3-dimensional (3D) reconstruction of
      echocardiography images provides a tool for the direct measurement of cardiac
      chambers, not based on geometric assumptions. The aim of this research study was
      to determine the accuracy of 3D echocardiography (3DE) to measure RV volumes in
      pediatric patients with secundum atrial septal defects, compared with direct
      volume measurements performed during the intervention. We performed 3DE study in
      the operating department, with the patient anesthetized, intubated, and
      ventilated before the surgical procedure. Sequential 2-dimensional
      echocardiographic images for subsequent 3D rendering were acquired using an
      ultrasound machine with a transthoracic 4-MHz rotational or 5-MHz transesophageal
      omniplane probe; in the last 5 patients a machine was used that was equipped with
      a 3600-crystal real-time 3D probe. To validate the 3DE measurements, these were
      compared with the volume of the RV directly measured in the operating department,
      at the end of the surgical procedure, injecting saline solution through the
      tricuspid valve, using a graduate syringe. Among 25 pediatric patients enrolled
      in the study, with an age range of 1 and 14 years (mean 4 years) and a weight
      range of 8.5 to 57.4 kg (mean 18.6 kg), in 23 a mean of 3 echocardiographic
      acquisitions were performed and compared with the direct measurement. A close
      comparison was found between RV volumes measured by 3DE and direct volume
      measurements (P < .00001). The regression line, shifted toward the y axis, which
      describes the 3DE volumes, indicated that the echocardiographic measures
      overestimate the surgical ones. In our study this overestimation had the mean of
      9% with values comprised between 3% and 19%. The coefficient of repeatability was
      4.79 mL with all the values within this range (2 SD of the mean). We conclude
      that 3DE provides an accurate measurement of RV volume in pediatric patients with
      RV volume overload. It is a reliable, noninvasive, and nongeometric method of
      evaluation of the volume of this chamber, and can be considered a precious tool
      in the armamentarium of the pediatric cardiologist.

PMID- 17555934
TI  - Impaired longitudinal myocardial velocities in patients with growth hormone
      deficiency improves after hormone replacement therapy.
AB  - Cardiac parameters in growth hormone (GH) deficiency and the effects of GH
      replacement treatment (GHRT) are still controversial. We investigated 19 adult
      patients (mean age: 45 +/- 10 years, 7 male), with GH deficiency before and after
      12 months of GHRT. Twenty age- and sex-matched healthy individuals (mean age: 44
      +/- 12 years, 9 male) were taken as a control group. All participants underwent
      echocardiography both before and after GHRT. The patients before GHRT and control
      subjects had similar left ventricular sizes and ejection fraction whereas
      patients before GHRT had impaired diastolic indices of left ventricle. Peak
      systolic annular velocity, which identifies myocardial longitudinal systolic
      function, was lower in patients before GHRT than in the control subjects (0.08 +/
      0.01 vs 0.10 +/- 0.02, P < .05) and improved after GHRT (0.09 +/- 0.03, P <
      .05). Adult-onset GH deficiency is associated with normal left ventricular sizes
      and preserved ejection fraction whereas longitudinal systolic function obtained
      by Doppler tissue imaging is deteriorated, which improves with 12 months of GHRT.

PMID- 17555935
TI  - Left ventricular structure and function for postmyocardial infarction and heart
      failure risk stratification by three-dimensional echocardiography.

PMID- 17555936
TI  - Transmitral flow patterns and the presence of chronic kidney disease provide
      independent and incremental prognostic information in patients with heart failure
      and systolic dysfunction.
AB  - BACKGROUND: Transmitral flow patterns derived from Doppler echocardiography carry
      prognostic information in patients with chronic heart failure and systolic
      dysfunction. In such patients, chronic kidney disease (CKD) defined as a
      reduction in estimated glomerular filtration rate less than 60 mL/min/1.73 m(2)
      is frequent, but its prognostic impact relative to that of transmitral flow
      patterns is unknown. METHODS: This prospective study enrolled 292 patients with
      stable chronic heart failure and systolic dysfunction (mean ejection fraction 30
      +/- 10), of whom 148 had CKD. Echocardiographic measurements comprised left
      ventricular dimensions/volumes, ejection fraction, the ratio of early (E) to late
      (A) transmitral flow velocity, deceleration time, and tissue Doppler mitral
      annular velocities. The mitral filling pattern (FP) was classified as either
      restrictive FP (RFP) or non-RFP. A cardiac event (cardiac death or urgent cardiac
      transplantation) was defined as combined study end point. RESULTS: During a
      follow-up of 497 +/- 373 days, 45 patients had a cardiac event (cardiac death, n
      = 42; urgent cardiac transplantation, n = 3). On multivariate Cox analysis
      including clinical and echocardiographic variables, independent prognostic
      predictors were RFP (hazard ratio: 2.77, 95% confidence interval 1.28-6.09), CKD
      (hazard ratio: 2.79, 95% confidence interval 1.24-6.28), and left atrial
      diameter. In patients with RFP, the prognosis was markedly worse in the presence
      of CKD as compared with the absence (event-free survival of 23% vs 83%, P = .03).
      Similarly, in patients with non-RFP, outcome was worse in the presence of CKD
      (event-free survival of 71% vs 88%, P = .003). CONCLUSIONS: In patients with
      chronic heart failure and systolic dysfunction, the presence of CKD adds
      incremental value to transmitral flow patterns in determining the prognosis.

PMID- 17555937
TI  - Assessment of mitral annulus size and function by real-time 3-dimensional
      echocardiography in cardiomyopathy: comparison with magnetic resonance imaging.
AB  - OBJECTIVE: We sought to assess mitral annular (MA) size and function in
      hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) using real
      time 3-dimensional (3D) echocardiography (RT3DE). METHODS: The study included 30
      patients with HCM, 20 patients with DCM, and 30 control subjects. RT3DE
      measurements included end-systolic and end-diastolic MA area (MAA) (MAA(3D)), MA
      diameter(3D), MA fractional area change (MAFAC), and MA fractional shortening. In
      subgroup of 50 patients, magnetic resonance imaging (MRI) was used for MAA(MRI)
      and MA diameter(MRI) measurement. RESULTS: End-diastolic MAA(3D) was larger in
      HCM than in control group (P < .0001). Higher MAFAC and MA fractional shortening
      were present in HCM than in control group (P = .001 and P = .006, respectively).
      End-systolic and end-diastolic MAA(3D) in DCM were higher than in HCM and control
      groups (P < .0001). Lower MAFAC and MA fractional shortening were present in DCM
      than in HCM and control groups (P < .0001). MAFAC correlated well with left
      ventricular function in control subjects (r = 0.94, P < .0001), whereas
      correlation was less in DCM (r = 0.53, P = .02) and HCM (r = 0.42, P < .01).
      RT3DE and MRI measurements were comparable. CONCLUSION: RT3DE assessment of MA
      size and function in control subjects and patients with cardiomyopathy is
      accurate and well correlated with MRI.

PMID- 17555938
TI  - Usefulness of real-time 3-dimensional echocardiography for the evaluation of
      coronary artery morphology in patients with Kawasaki disease.
AB  - OBJECTIVES: This study was designed to evaluate the usefulness of real-time 3
      dimensional echocardiography (RT-3DE) for evaluating coronary artery morphology
      in patients with Kawasaki disease. BACKGROUND: The diagnosis of coronary artery
      morphology in the acute phase of the disease is of prime importance for
      evaluating the likelihood of cardiovascular sequelae. Occasionally, visualization
      of the right coronary artery and bifurcated regions, including the circumflex
      artery, has proved challenging with traditional echocardiographic methods.
      METHODS: A total of 111 patients with Kawasaki disease were studied. Coronary
      aneurysms were detected in 8 patients (4 had giant aneurysms), and coronary
      dilation was found in 11 patients. Coronary artery visualization was evaluated
      and scored as 1 of 4 grades, 0 to 3 points, for both 2-dimensional
      echocardiography (2DE) and RT-3DE. Evaluation criteria for each coronary artery
      were defined according to the American Heart Association classification of
      coronary angiographic features. Total scores for each patient and for individual
      coronary branches were compared between 2DE and RT-3DE. RESULTS: The total scores
      for coronary artery visualization were, respectively, showing a significantly
      higher score for RT-3DE than for 2DE (P < .01). A mural thrombus could be clearly
      delineated in the giant coronary aneurysms by RT-3DE. CONCLUSIONS: RT-3DE is
      superior to 2DE for coronary artery visualization. This diagnostic system is
      expected to improve the screening of coronary artery abnormalities in Kawasaki
      disease.

PMID- 17555939
TI  - Diplopia after topical pharyngeal anesthesia for transesophageal
      echocardiography.

PMID- 17555940
TI  - Left ventricular noncompaction mimicking peripartum cardiomyopathy.

PMID- 17555941
TI  - Speckle tracking echocardiography is a sensitive tool for the detection of
      myocardial ischemia: a pilot study from the catheterization laboratory during
      percutaneous coronary intervention.
AB  - Analysis of rotational myocardial motion has been reported to be a sensitive
      index of myocardial ischemia. In this study, circumferential and radial
      myocardial strain and displacement was monitored during angioplasty balloon
      induced myocardial ischemia in 8 patients undergoing percutaneous coronary
      intervention. The circumferential and radial variables were measured
      simultaneously in parasternal short-axis view at the papillary muscle level using
      the recently introduced speckle tracking echocardiography technique that allows 2
      dimensional, angle-independent, real-time evaluation of the myocardial motion (2
      dimensional strain modality). Acute regional myocardial ischemia caused a
      significant reduction of circumferential (-35.6 +/- 23.1%) and radial (-27.1 +/-
      23.2%) strain and displacement (-49.6 +/- 27.2% and -43.2 +/- 26.8%,
      respectively). Simultaneously, time to the respective peak systolic values became
      significantly prolonged, the circumferential ischemic response in temporal domain
      being more pronounced (P < .05). Speckle tracking echocardiography-based analysis
      of rotational myocardial motion has a potential to become an efficient clinical
      bedside tool in the detection of acute ischemic regional myocardial dysfunction.

PMID- 17555942
TI  - Acute thrombosis of a prosthetic mitral valve: a lesson in anticoagulation.
AB  - Prosthetic heart valve thrombosis is a potentially life-threatening complication
      of low anticoagulation. We present a case of acute prosthetic mitral valve
      thrombosis in a patient whose anticoagulation was inadequate after phenindione
      was changed to low molecular weight heparin. We discuss the diagnosis and
      treatment of this condition and highlight the danger of long-term low molecular
      weight heparin use in patients with prosthetic heart valves, especially those in
      the mitral position. We review the current guidelines for anticoagulation of
      prosthetic heart valves and discuss potential treatment options if adequate
      anticoagulation is not achieved by oral anticoagulant alone.

PMID- 17555943
TI  - Opposing effects of Bad phosphorylation at two distinct sites by Akt1 and JNK1/2
      on ischemic brain injury.
AB  - Increasing evidence suggests that the Bcl-2 family proteins play pivotal roles in
      regulation of the mitochondria cell-death pathway on transient cerebral ischemia.
      Bad, a BH3-only proapoptotic Bcl-2 family protein, has been shown to be
      phosphorylated extensively on serine by kinds of kinases. However, the exact
      mechanisms of the upstream kinases in regulation of Bad signaling pathway remain
      unknown. Here, we reported that Bad could be phosphorylated not only by Akt1 but
      also by JNK1/2 after transient global ischemia in rat hippocampal CA1 region. Our
      data demonstrated that Akt1 mediated the phosphorylation of Bad at serine 136,
      which increased the interaction of serine 136-phosphorylated Bad with 14-3-3
      proteins and prevented the dimerization of Bad with Bcl-Xl, inhibited the release
      of cytochrome c to the cytosol and the death effector caspase-3 activation,
      leading to the survival of neuron. In contrast, JNK1/2 induced the
      phosphorylation of Bad at a novel site of serine 128 after brain
      ischemia/reperfusion, which inhibited the interaction of PI3K/Akt-induced serine
      136-phosphorylated Bad with 14-3-3 proteins, thereby promoted the apoptotic
      effect of Bad. In addition, activated Akt1 inhibited the activation of Bad(S128)
      through downregulating JNK1/2 activation, thus inhibiting JNK-mediated Bad
      apoptosis pathway. Furthermore, the fate of cell to survive or to die was
      determined by a balance between prosurvival and proapoptotic signals. Taken
      together, our studies reveal that Bad phosphorylation at two distinct sites
      induced by Akt1 and JNK1/2 have opposing effects on ischemic brain injury, and
      present the possibility of Bad as a potential therapeutic target for stroke
      treatment.

PMID- 17555944
TI  - The PIP5K2A gene and schizophrenia in the Chinese population--a case-control
      study.
AB  - Results from a number of molecular and pharmacological studies suggest that the
      phosphatidylinositol-4-phosphate 5-kinase IIalpha (PIP5K2A) gene may be involved
      in the development of schizophrenia. A recent family-based transmission
      disequilibrium test in the German and Israeli populations found that four single
      nucleotide polymorphisms, rs1417374, rs10828317, rs746203 and rs8341 in this gene
      or nearby intergenic regions are significantly associated with schizophrenia. The
      objective of our study was to investigate whether these four SNPs are also
      associated with schizophrenia in the Chinese population. Our study found that SNP
      rs8341 (p=0.0045, Odds Ratio=1.415, 95%CI=1.113-1.799 for the minor allele) and a
      haplotype (p=0.0039, Odds Ratio=1.440, 95%CI=1.123-1.845) are significantly
      associated with schizophrenia. Our results confirm that the PIP5K2A gene merits
      further study as a susceptible gene for schizophrenia.

PMID- 17555945
TI  - In vitro activity of voriconazole against dermatophytes, Scopulariopsis
      brevicaulis and other opportunistic fungi as agents of onychomycosis.
AB  - Using a reference microdilution method, we studied the antifungal susceptibility
      to voriconazole and fluconazole of 304 clinical isolates from four species of
      onychomycosis-causing dermatophytes, 196 isolates of dermatophytes not related to
      nail infection as well as Scopulariopsis brevicaulis, Fusarium spp. and
      Scytalidium dimidiatum. Results showed a high antifungal activity of voriconazole
      against dermatophytes (geometric mean minimal inhibitory concentration (MIC)=1.14
      microg/mL; MIC for 50% of the organisms (MIC(50))=0.062 miccrog/mL; MIC for 90%
      of the organisms (MIC(90))=0.25 microg/mL). For S. brevicaulis, the in vitro
      activity of voriconazole was considerably lower (geometric mean MIC=8.52
      microg/mL; MIC(50) and MIC(90)=16 microg/mL). Although voriconazole is not among
      the drugs recommended for the management of onychomycosis, it can be a useful
      alternative for recalcitrant infections.

PMID- 17555946
TI  - Cure of Candida glabrata native tricuspid valve endocarditis by continuous
      infusion of conventional amphotericin B in a patient with nephrotic syndrome.

PMID- 17555948
TI  - Chitosan nanoparticle as protein delivery carrier--systematic examination of
      fabrication conditions for efficient loading and release.
AB  - Chitosan nanoparticles fabricated via different preparation protocols have been
      in recent years widely studied as carriers for therapeutic proteins and genes
      with varying degree of effectiveness and drawbacks. This work seeks to further
      explore the polyionic coacervation fabrication process, and associated processing
      conditions under which protein encapsulation and subsequent release can be
      systematically and predictably manipulated so as to obtain desired effectiveness.
      BSA was used as a model protein which was encapsulated by either incorporation or
      incubation method, using the polyanion tripolyphosphate (TPP) as the coacervation
      crosslink agent to form chitosan-BSA-TPP nanoparticles. The BSA-loaded chitosan
      TPP nanoparticles were characterized for particle size, morphology, zeta
      potential, BSA encapsulation efficiency, and subsequent release kinetics, which
      were found predominantly dependent on the factors of chitosan molecular weight,
      chitosan concentration, BSA loading concentration, and chitosan/TPP mass ratio.
      The BSA loaded nanoparticles prepared under varying conditions were in the size
      range of 200-580nm, and exhibit a high positive zeta potential. Detailed
      sequential time frame TEM imaging of morphological change of the BSA loaded
      particles showed a swelling and particle degradation process. Initial burst
      released due to surface protein desorption and diffusion from sublayers did not
      relate directly to change of particle size and shape, which was eminently
      apparent only after 6h. It is also notable that later stage particle degradation
      and disintegration did not yield a substantial follow-on release, as the
      remaining protein molecules, with adaptable 3-D conformation, could be tightly
      bound and entangled with the cationic chitosan chains. In general, this study
      demonstrated that the polyionic coacervation process for fabricating protein
      loaded chitosan nanoparticles offers simple preparation conditions and a clear
      processing window for manipulation of physiochemical properties of the
      nanoparticles (e.g., size and surface charge), which can be conditioned to exert
      control over protein encapsulation efficiency and subsequent release profile. The
      weakness of the chitosan nanoparticle system lies typically with difficulties in
      controlling initial burst effect in releasing large quantities of protein
      molecules.

PMID- 17555947
TI  - A multicentre, randomized, naturalistic, open-label study between aripiprazole
      and standard of care in the management of community-treated schizophrenic
      patients Schizophrenia Trial of Aripiprazole: (STAR) study.
AB  - BACKGROUND: Naturalistic effectiveness trials of atypical antipsychotics are
      needed to provide broader information on efficacy, safety, and tolerability in
      patients with schizophrenia treated in a community practice setting. METHOD: In
      this 26-week, open-label, multicentre study, patients with schizophrenia
      requiring a switch in antipsychotic medication because current medication was not
      well tolerated and/or clinical symptoms were not well controlled were randomized
      to receive aripiprazole or an atypical antipsychotic standard of care (SOC)
      treatment (i.e., olanzapine, quetiapine, or risperidone based on the
      investigator's judgment of the optimal treatment for the individual patient and
      the patient's prior response to antipsychotic medication). The primary objective
      was to compare the effectiveness of a 26-week treatment of aripiprazole versus
      SOC, as measured by the Investigator Assessment Questionnaire (IAQ) total score
      at Week 26 last observation carried forward (LOCF) (primary endpoint), a
      validated measure that monitors relief or worsening of 10 key symptoms associated
      with the psychopathology of schizophrenia and side effects of antipsychotic
      treatment. Secondary objectives were to further assess effectiveness using the
      Clinical Global Impression - Global Improvement (CGI-I) and Clinical Global
      Impression - Severity of Illness scale, to assess time to treatment
      discontinuation, patient preference of medication, quality of life, and the
      tolerability of aripiprazole compared with SOC. RESULTS: Aripiprazole treatment
      (n=268) resulted in significantly better effectiveness than SOC treatment (n=254;
      P<0.001; Week 26 LOCF) as evidenced by the IAQ total score beginning at Week 4
      (the first assessment point) and sustained through Week 26. A similar
      relationship was demonstrated among patients who completed the study (observed
      cases analysis); aripiprazole was associated with significantly better
      effectiveness at all time points with a greater differential effect from SOC over
      time. Patients treated with aripiprazole also demonstrated significantly greater
      improvements on the CGI-I scale (responder rate, P=0.009 at Week 26 LOCF), as
      well as on quality of life (Quality of Life scale total score; P<0.001 at Week
      26). Furthermore, a significantly higher proportion of patients receiving
      aripiprazole rated their study medication as "much better" on the Preference of
      Medication Questionnaire (POM) scale than their pre-study medication compared
      with SOC patients (P<0.001; Week 26). Time to treatment discontinuation and rates
      of discontinuation due to adverse events were similar in both treatment groups.
      The incidence of patients with one or more extrapyramidal symptom (e.g.,
      akathisia, dystonia, parkinsonian events, and residual events) was higher in
      patients receiving aripiprazole compared with patients treated with SOC (13.5%
      vs. 5.6%); however, a higher proportion of patients in the SOC-treated group had
      clinically significant weight gain (21.2% vs. 7.3% for aripiprazole) and
      potentially clinically relevant elevated fasting levels of total cholesterol, low
      density lipoprotein cholesterol, triglycerides, and serum prolactin compared with
      patients receiving aripiprazole. CONCLUSIONS: Aripiprazole is an effective
      atypical antipsychotic for the treatment of schizophrenia, demonstrating better
      effectiveness than SOC agents used in this study in patients for whom a switch in
      antipsychotic medication was warranted.

PMID- 17555949
TI  - [Renal tubular dysgenesis and mutation in the renin gene].
AB  - Renal tubular dysgenesis is a severe and rare disorder of the renal development
      characterized by fetal anuria, oligohydramnios and early death from pulmonary
      hypoplasia and refractory arterial hypotension. We report on a female patient who
      presented with anuria in the neonatal period, requiring peritoneal dialysis until
      5 months of age with unexpected diuresis recovery at 2 months of age. Clinical,
      histological and pathophysiological issues are discussed for this disease related
      to a mutation in the renin gene.

PMID- 17555950
TI  - Development and comparison of four sleep spindle detection methods.
AB  - OBJECTIVE: The objective of the present work was to develop and compare methods
      for automatic detection of bilateral sleep spindles. METHODS AND MATERIALS: All
      night sleep electroencephalographic (EEG) recordings of 12 healthy subjects with
      a median age of 40 years were studied. The data contained 6043 visually scored
      bilateral spindles occurring in frontopolar or central brain location. In the
      present work a new sigma index for spindle detection was developed, based on the
      fast Fourier transform (FFT) spectrum, aiming at approximating our previous fuzzy
      spindle detector. The sigma index was complemented with spindle amplitude
      analysis, based on finite impulse response (FIR) filtering, to form of a
      combination detector of bilateral spindles. In this combination detector, the
      spindle amplitude distribution of each recording was estimated and used to tune
      two different amplitude thresholds. This combination detector was compared to
      bilaterally extracted sigma indexes and fuzzy detections, which aim to be
      independent of absolute spindle amplitudes. As a fourth method a fixed spindle
      amplitude detector was included. RESULTS: The combination detector provided the
      best overall performance; in S2 sleep a 70% true positive rate was reached with a
      specificity of 98.6%, and a false-positive rate of 32%. The bilateral sigma
      indexes provided the second best results, followed by fuzzy detector, while the
      fixed amplitude detector provided the poorest results so that in S2 sleep a 70%
      true positive rate was reached with a specificity of 97.7% and false-positive
      rate of 46%. The spindle amplitude distributions automatically determined for
      each recording by the combination detector were compared to amplitudes of
      visually scored spindles and they proved to correspond well. Inter-hemispheric
      amplitude variation of visually scored bilateral spindles is also presented.
      CONCLUSION: Flexibility is beneficial in the detection of bilateral spindles. The
      present work advances automated spindle detection and increases the knowledge of
      bilateral sleep spindle characteristics.

PMID- 17555952
TI  - Resistance to obesity and resistance to atherosclerosis: is there a metabolic
      link?
AB  - AIM: This review deals with the question whether resistance to obesity affects
      resistance to atherosclerosis. DATA SYNTHESIS: Resistance to diet-induced obesity
      in inbred mouse strains involves an adequate response to Leptin, the main
      regulator of the energy balance cycle. Leptin, an adipokine with both central and
      peripheral targets, regulates food intake and energy expenditure. Adequate
      response to leptin involves repression of stearoyl-CoA desaturase, activation of
      Amp-activated protein-kinase and uncoupling proteins, resulting in fatty acid
      oxidation and energy expenditure. Most of the obesity-resistant strains are also
      resistant to atherosclerosis, but so far no information concerning the response
      to the leptin cycle is available in these strains when bred onto a LDLR(-/-) or
      apoE(-/-) background. Recent studies in mouse strains on an atherosclerosis
      permissive background have identified genetic links between obesity and
      atherosclerosis. Moreover, information derived from studies on mice was applied
      in order to learn about the metabolic effectors in humans and is included in this
      review. CONCLUSIONS: The data presented in this review provide recent information
      concerning metabolic pathways that play an important role in the regulation of
      energy balance, a prerequisite for resistance to obesity. Hopefully they will
      provide a background for future genetic studies involved in resistance to
      atherosclerosis.

PMID- 17555951
TI  - Interaction between the uncoupling protein 2 -866G>A gene variant and cigarette
      smoking to increase oxidative stress in subjects with diabetes.
AB  - BACKGROUND AND AIMS: Increased oxidative stress is associated with coronary heart
      disease (CHD). The mitochondrial uncoupling protein-2 (UCP2) negatively regulates
      reactive oxygen species generation. We have observed that a common variant (
      866G>A) in the promoter region of UCP2 is associated with increased CHD risk in
      healthy men and increased oxidative stress in diabetic men with CHD. The aim of
      the current study was to test the hypothesis that this variant might interact
      with smoking (an environmental stress) to influence plasma markers of oxidative
      stress. METHODS AND RESULTS: Amongst 453 Caucasian diabetic men there was a
      significant interaction (p=0.001) between genotype and smoking in determining
      plasma Total AntiOxidant Status (TAOS). Current smokers with the -866AA genotype
      had the lowest TAOS (indicating higher oxidative stress) of all subjects (AA vs.
      GG: 32.00+/-17.4% vs. 45.8+/-12.6%, p=0.04). In a sub-sample of 20 subjects (10
      GG, 10 AA) matched for baseline characteristics, plasma markers of oxidative
      stress in current smokers were significantly higher in AA compared to GG subjects
      (TAOS 36.8+/-9.5% vs. 51.4+/-9.5%, p=0.04; F(2)-isoprostanes 1133.6+/-701.2 pg
      ml(-1) vs. 500.8+/-64.7 pg ml(-1), p=0.04). CONCLUSIONS: This study demonstrates
      an interaction between the UCP2 -866G>A variant and smoking to increase oxidative
      stress in vivo.

PMID- 17555953
TI  - A modified Ames assay reveals the mutagenicity of native cigarette mainstream
      smoke and its gas vapour phase.
AB  - The evaluation of the mutagenic activity of cigarette smoke is mostly based on
      studies with condensates or extracts in the standard Ames assay. These samples
      only insufficiently reflect the composition of the actual generated aerosol.
      Therefore, such atmospheres should be analysed in their native composition to
      gain a real signal of its mutagenic capacity. Based on the technical difficulties
      of testing native air contaminants, there are no accepted methods for effective
      exposure of bacteria under such conditions. Therefore, we established a new
      experimental approach for direct exposure of bacteria in a modified CULTEX system
      (Patent no. DE 19801763/PCT/EP99/00295) connected to a smoking machine. This
      allowed us to investigate the mutagenic activity of native mainstream smoke of
      the research cigarette K2R4F by exposure of Salmonella Typhimurium strains. In
      comparison to studies using the plate incorporation assay, the direct exposure of
      bacteria to smoke on the agar surface enhances contact to the aerosols. By using
      this modification of the Ames assay, we demonstrate that it is possible to
      analyse the effects of native whole smoke and the gas vapour phase of cigarettes
      directly and achieve a dose-dependent induction of revertants. In a number of
      experiments, the treatment of strains TA98 and TA100 with whole smoke and the gas
      vapour phase of K2R4F cigarettes resulted in the induction of revertants
      dependent on the dilution of smoke and the number of cigarettes smoked. Our
      alternative procedure of exposing bacteria directly to gases and complex mixtures
      offers new possibilities in the field of inhalation genotoxicology for the
      evaluation of genotoxicity in the Ames assay.

PMID- 17555954
TI  - Microtubular conductometric biosensor for ethanol detection.
AB  - A conductometric sensor using microtubules of polyaniline as transducer cum
      immobilization matrix is reported, capable of detecting ethanol in liquid phase.
      Enzyme ADH (alcohol dehydrogenase) and its coenzyme NAD+ have been used to
      improve the selectivity of the sensor. The sensor concept is based on the
      protonation of the polyaniline by the hydrogen ion produced in the enzyme
      catalyzed reaction, leading to changes in the electrical conductance of the
      polyaniline. The sensor works well on the physiological pH, can detect ethanol as
      low as 0.02% (v/v) (0.092 M) and has a linear trend at par healthcare guidelines.
      The sensor responses were measured in various permutation and combination of
      enzyme and coenzyme concentrations and site of immobilization. The sensor shows
      minor interference with other functional groups and alcohols. The possible causes
      for such interference have been discussed.

PMID- 17555955
TI  - What influences clinicians' operative preferences for women with breast cancer?
      An application of the discrete choice experiment.
AB  - INTRODUCTION: Little is known regarding cancer clinicians' treatment preferences.
      AIM: Determine the impact of pre-operative variables over specialist breast
      clinicians' operative preferences using discrete choice experiment methodology.
      METHODS: Cross-sectional survey of operative preferences to hypothetical
      scenarios based on: patient age, bra cup size, cancer size, site and focality.
      RESULTS: 73% response rate (68/93). Multinomial logistic regression across
      scenarios (n=1695) with allowance for response clustering, comparing equal
      preference for mastectomy and breast conservation surgery (BCS) with preference
      for mastectomy or BCS. Increasing patient age, cancer size, central site, multi
      focality and reducing cup size, all associated with preference for mastectomy,
      over equal preference, over BCS (p<0.001). Doctors preferred specific treatments,
      females and nurses avoided mastectomy (p=0.015 and p<0.001 respectively).
      CONCLUSIONS: Clinician preferences were predominantly treatment guideline
      congruent, but significantly influenced by patient age, clinician gender and
      occupation. This methodology is capable of elucidating treatment preferences and
      could be applied elsewhere where treatment options and practice variability
      exist.

PMID- 17555956
TI  - Copper removal from wastewater using spent-grain as biosorbent.
AB  - The removal of Cu(II) ions from aqueous solutions using spent-grain was studied.
      The experimental data fitted the Langmuir isotherm and the maximum adsorption
      capacity of spent-grain was determined to be 10.47 mg g(-1) dry weight (pH 4.2).
      Kinetic studies showed the adsorption process followed pseudo second-order rate
      model. Column studies with synthetic Cu(II) solutions were used to investigate
      the effects of Cu(II) ion concentration, initial pH, flow rate and the presence
      of EDTA on the Cu(II) removal performance. When treating the spent-lees, the
      wastewater from the whisky distilling industry, the reduction of Cu(II) uptake
      capacity to 77.7% (solution pH adjusted to 4.5 with 1N NaOH) and 31.6% (pH 3.8
      without adjustment) was observed compared to Cu(II) uptake capacity when treating
      synthetic Cu(II) solution. On the basis of the results and that spent-grain is an
      abundant and by-product from the whisky distilling industry we suggest that it
      can be economically and effectively applied as a biosorbent for the removal of
      Cu(II) ions from distilling wastewaters.

PMID- 17555957
TI  - An integrated process for the treatment of CETP wastewater using coagulation,
      anaerobic and aerobic process.
AB  - The aim of this study was to treat the wastewater collected from equalization
      tank of Common Effluent Treatment Plant (CETP), which was a mixture of waste
      coming from 525 small-scale industries manufacturing textile and dyestuff
      intermediate, pigments and pharmaceuticals. Initially a pretreatment using ferric
      chloride and lime was carried out to increase the biodegradability (BOD(5)/COD)
      of the effluent, which showed color removal of 74% and COD reduction of 75% at a
      concentration of 10 and 4 g/L. respectively. The biological treatment system
      using anaerobic fixed film reactor was investigated as secondary treatment. A
      mixture of bacterial consortium DMAB and cowdung slurry was used for the
      formation of biofilm. The effect of hydraulic retention time (HRT) and organic
      loading rate (OLR) on the efficiency of treatment of anaerobic reactor was
      analysed. Subsequent aerobic treatment after anaerobic step using aerobic culture
      Pseudomonas aeroginosa helped in further removal of COD and color. Formation of
      aromatic amines during anaerobic treatment was mineralized by sequential aerobic
      treatment.

PMID- 17555958
TI  - Comparison between pine bark and coconut husk sorption capacity of metals and
      nitrate when mixed with sewage sludge.
AB  - Waste products such as biosolids and wood wastes have been frequently used in
      container production of plants. The use of biosolids in agriculture is a
      beneficial mean of recycling the by-products of waste-water treatment. However,
      care must be taken to avoid environmental or human health problems via run-off
      and leaching. The objective of this work is to compare the retention capacity of
      cadmium, lead, zinc and nitrate between pine bark (PB) and coconut fibre (F) when
      mixed with increasing amounts of composted sewage sludge (CSS) (0%, 15% and 30%
      (v/v)). Substrates were packed into leaching columns and irrigated with deionised
      water every 2 days. Leachates were collected during 1 month, and nitrate, Zn, Cd,
      Pb, EC and pH were monitored along the experiment. PB columns leached lower
      amount of nitrate than the coconut fibre ones. The same trend was observed for
      Zn, Cd and Pb. It could be said, that in order to minimize the environmental
      risks of using sewage sludges our results indicate that it is preferred to mix
      the sludge with pine bark instead than with coconut husk.

PMID- 17555959
TI  - Cycloalkanediamine derivatives as novel blood coagulation factor Xa inhibitors.
AB  - This paper describes the synthesis of orally available potent fXa inhibitors 2
      and 3 by modification of the piperazine part of lead compound 1. Carbonyl
      derivative 3 showed potent fXa activity but not sulfonyl derivative 2. Among the
      compounds synthesized, cyclohexane derivatives 3g and 3h and cycloheptane
      derivative 3j had potent anticoagulant activity as well as anti-fXa activity.
      Synthetic study of the optical isomers of 3g demonstrated that (-)-3g had more
      potent activity.

PMID- 17555960
TI  - Praziquantel derivatives I: Modification of the aromatic ring.
AB  - Several analogues of the potent anthelmintic praziquantel were prepared with
      variation in the aromatic ring. The biological activity of these analogues was
      evaluated and compared against known analogues. Amination of the ring was
      tolerated while other variations were not. These results have important
      implications for drug development for schistosomiasis.

PMID- 17555961
TI  - Heterocyclic alpha-helix mimetics for targeting protein-protein interactions.
AB  - The design and synthesis of alpha-helix peptidomimetics using inverse electron
      demand Diels-Alder reactions is described. The potency of the resulting
      pyridazine-based library to disrupt the Bak/Bcl-X(L) interaction was tested using
      an in vitro fluorescence polarization assay.

PMID- 17555962
TI  - Design of novel histone deacetylase inhibitors.
AB  - Histone deacetylase (HDAC) inhibitors that target Class I and Class II HDACs are
      of synthetic and therapeutic interest and ongoing clinical studies indicate that
      they show great promise for the treatment of cancer. Moreover, Zolinza
      (vorinostat) was recently approved by the FDA for the treatment of the cutaneous
      manifestations of cutaneous T-cell lymphoma [Nat. Rev. Drug Disc. 2007, 6, 21].
      As part of a broader effort to more fully explore the structure-activity
      relationships (SAR) of HDAC inhibitors, we sought to identify novel HDAC
      inhibitor structures through iterative design by utilizing low affinity ligands
      as synthetic starting points for SAR development. Novel and potent HDAC
      inhibitors have been identified using this approach and herein we report the
      optimization of the recognition elements of a novel series of malonyl-derived
      HDAC inhibitors.

PMID- 17555963
TI  - Novel ebselen-porphyrin conjugates: synthesis and nucleic acid interaction study.
AB  - Novel porphyrins bearing ebselen (2-phenyl-1,2-benzisoselenazol-3[2H]-one) moiety
      were synthesized and characterized. Their interactions with herring sperm DNA
      were studied by means of UV-visible, fluorescence, circular dichroism
      spectroscopy, and gel electrophoresis.

PMID- 17555964
TI  - Clockwork orange encodes a transcriptional repressor important for circadian
      clock amplitude in Drosophila.
AB  - Gene transcription is a central timekeeping process in animal clocks. In
      Drosophila, the basic helix-loop helix (bHLH)-PAS transcription-factor
      heterodimer, CLOCK/CYCLE (CLK/CYC), transcriptionally activates the clock
      components period (per), timeless (tim), Par domain protein 1 (Pdp1), and vrille
      (vri), which feed back and regulate distinct features of CLK/CYC function.
      Microarray studies have identified numerous rhythmically expressed transcripts,
      some of which are potential direct CLK targets. Here we demonstrate a circadian
      function for one such target, a bHLH-Orange repressor, CG17100/CLOCKWORK ORANGE
      (CWO). cwo is rhythmically expressed, and levels are reduced in Clk mutants,
      suggesting that cwo is CLK activated in vivo. cwo mutants display reduced
      amplitude molecular and behavioral rhythms with lengthened periods. Molecular
      analysis suggests that CWO acts, in part, by repressing CLK target genes. We
      propose that CWO acts as a transcriptional and behavioral rhythm amplifier.

PMID- 17555965
TI  - Genetic structure and extinction of the woolly mammoth, Mammuthus primigenius.
AB  - The interval since circa 50 Ka has been a period of significant species
      extinctions among the large mammal fauna. However, the relative roles of an
      increasing human presence and a synchronous series of complex environmental
      changes in these extinctions have yet to be fully resolved. Recent analyses of
      fossil material from Beringia have clarified our understanding of the
      spatiotemporal pattern of Late Pleistocene extinctions, identifying periods of
      population turnover well before the last glacial maximum (LGM: circa 21 Ka) or
      subsequent human expansion. To examine the role of pre-LGM population changes in
      shaping the genetic structure of an extinct species, we analyzed the
      mitochondrial DNA of woolly mammoths in western Beringia and across its range. We
      identify genetic signatures of a range expansion of mammoths, from eastern to
      western Beringia, after the last interglacial (circa 125 Ka), and then an
      extended period during which demographic inference indicates no population-size
      increase. The most marked change in diversity at this time is the loss of one of
      two major mitochondrial lineages.

PMID- 17555966
TI  - Drosophila stathmin is required to maintain tubulin pools.
AB  - Stathmin, or Oncoprotein 18 (Op18), is the founding member of a phosphoprotein
      family that can regulate the microtubule cytoskeleton by sequestering tubulin and
      promoting microtubule catastrophe. Stathmin is subject to spatially and
      temporally controlled regulatory phosphorylation, which inhibits its interaction
      with tubulin. Drosophila Stathmin has similar properties to the mammalian
      proteins. We find that Drosophila Stathmin is required for specific microtubule
      dependent processes: maintenance of oocyte identity within a germline cyst and
      localization of polarity determinants. Unexpectedly, microtubules are less
      abundant in stathmin mutant cells compared to normal cells, showing that a key
      function of Stathmin in vivo is the long-term maintenance of the microtubule
      cytoskeleton. The microtubule network re-forms more slowly after coldshock in
      stathmin mutant follicle cells. Surprisingly, stathmin mutant animals and tissues
      show a marked decrease in total tubulin-protein levels, and this might explain
      the effect on the microtubule cytoskeleton. Stathmin overexpression also
      increases tubulin protein. Free alpha- and beta-tubulin have been shown to
      negatively autoregulate their own synthesis. We suggest that Stathmin serves to
      maintain a noninhibitory, soluble, and releasable tubulin pool.

PMID- 17555967
TI  - Distinct dynamics of HISTONE3 variants between the two fertilization products in
      plants.
AB  - Sexual reproduction involves epigenetic reprogramming comprising DNA methylation
      and histone modifications. In addition, dynamics of HISTONE3 (H3) variant H3.3
      upon fertilization are conserved in animals, suggesting an essential role. In
      contrast to H3, H3.3 marks actively transcribed regions of the genome and can be
      deposited in a replication-independent manner. Although H3 variants are conserved
      in plants, their dynamics during fertilization have remained unexplored. We
      overcame technical limitations to live imaging of the fertilization process in
      Arabidopsis thaliana and studied dynamics of the male-gamete-specific H3.3 and
      the centromeric Histone Three Related 12 (HTR12). The double-fertilization
      process in plants produces the zygote and the embryo-nourishing endosperm. We
      show that the zygote is characterized by replication-independent removal of
      paternal H3.3 and homogeneous incorporation of parental chromatin complements. In
      the endosperm, the paternal H3.3 is passively diluted by replication while the
      paternal chromatin remains segregated apart from the maternal chromatin
      (gonomery). Hence epigenetic regulations distinguish the two products of
      fertilization in plants. H3.3-replication-independent dynamics and gonomery also
      mark the first zygotic divisions in animal species. We thus propose the
      convergent selection of parental epigenetic imbalance involving H3 variants in
      sexually reproducing organisms.

PMID- 17555968
TI  - Transmission of multiple traditions within and between chimpanzee groups.
AB  - Field reports provide increasing evidence for local behavioral traditions among
      fish, birds, and mammals. These findings are significant for evolutionary biology
      because social learning affords faster adaptation than genetic change and has
      generated new (cultural) forms of evolution. Orangutan and chimpanzee field
      studies suggest that like humans, these apes are distinctive among animals in
      each exhibiting over 30 local traditions. However, direct evidence is lacking in
      apes and, with the exception of vocal dialects, in animals generally for the
      intergroup transmission that would allow innovations to spread widely and become
      evolutionarily significant phenomena. Here, we provide robust experimental
      evidence that alternative foraging techniques seeded in different groups of
      chimpanzees spread differentially not only within groups but serially across two
      further groups with substantial fidelity. Combining these results with those from
      recent social-diffusion studies in two larger groups offers the first
      experimental evidence that a nonhuman species can sustain unique local cultures,
      each constituted by multiple traditions. The convergence of these results with
      those from the wild implies a richness in chimpanzees' capacity for culture, a
      richness that parsimony suggests was shared with our common ancestor.

PMID- 17555969
TI  - Exomethylene pyranonucleosides: efficient synthesis and biological evaluation of
      1-(2,3,4-trideoxy-2-methylene-beta-d-glycero-hex-3-enopyranosyl)thymine.
AB  - A new series of unsaturated pyranonucleosides with an exocyclic methylene group
      and thymine as heterocyclic base have been designed and synthesized. d-Galactose
      (1) was readily transformed in three steps into the corresponding 1-(beta-d
      galactopyranosyl)thymine (2). Selective protection of the primary hydroxyl group
      of 2 with a t-butyldimethylsilyl (TBDMS) group, followed by specific acetalation,
      and oxidation gave 1-(6-O-t-butyldimethylsilyl-3,4-O-isopropylidene-beta-d-lyxo
      hexopyranosyl-2-ulose)thymine (5). Wittig reaction of the ketonucleoside 5,
      deprotection and tritylation of the 6'-hydroxyl group gave 1-(2-deoxy-2-methylene
      6-O-trityl-beta-d-lyxo-hexopyranosyl)thymine (9). Exomethylene pyranonucleoside 9
      was converted to the olefinic derivative 10, which after detritylation afforded
      the title compound 1-(2,3,4-trideoxy-2-methylene-beta-d-glycero-hex-3
      enopyranosyl)thymine (11). These novel synthesized compounds were evaluated for
      antiviral activity against rotaviral infection and cytotoxicity in colon cancer.
      As compared to AZT, compounds 1-(2-deoxy-2-methylene-beta-d-lyxo
      hexopyranosyl)thymine (7) and 1-(beta-d-lyxo-hexopyranosyl-2-ulose)thymine (8)
      showed to be more efficient, in rotavirus infections and in treatment of colon
      cancer.

PMID- 17555970
TI  - Functional MAPT haplotypes: bridging the gap between genotype and neuropathology.
AB  - The microtubule-associated protein tau (MAPT) locus has long been associated with
      sporadic neurodegenerative disease, notably progressive supranuclear palsy and
      corticobasal degeneration, and more recently with Alzheimer's disease and
      Parkinson's disease. However, the functional biological mechanisms behind the
      genetic association have only now started to emerge. The genomic architecture in
      the region spanning MAPT is highly complex, and includes a approximately 1.8 Mb
      block of linkage disequilibrium (LD). The region is divided into two major
      haplotypes, H1 and H2, defined by numerous single nucleotide polymorphisms and a
      900 kb inversion which suppresses recombination. Fine mapping of the MAPT region
      has identified sub-clades of the MAPT H1 haplotype which are specifically
      associated with neurodegenerative disease. Here we briefly review the role of
      MAPT in sporadic and familial neurodegenerative disease, and then discuss recent
      work which, for the first time, proposes functional mechanisms to link MAPT
      haplotypes with the neuropathology seen in patients.

PMID- 17555971
TI  - What to expect after tricuspid valve replacement? Long-term results.
AB  - OBJECTIVE: Current knowledge in long-term results of tricuspid valve replacement
      is limited. Present study reviews our experience from a consecutive series.
      METHODS: Forty-two patients (16 male, 26 female; mean age: 33+/-15) underwent
      tricuspid valve replacement between March 1987 and December 2004. The etiology
      was rheumatic in 64%, Ebstein's anomaly in 31%, and endocarditis in 5%. Nineteen
      patients were in New York Heart Association (NYHA) Class III functional capacity
      (45%), and 13 in class IV (31%). Twenty patients (48%) underwent isolated
      tricuspid valve replacement. The remaining underwent combined (mitral and/or
      aortic) valve replacements. Tricuspid replacement device was mechanical in 31%
      and bioimplant in 69%. RESULTS: Hospital mortality was 26%. Rheumatic etiology,
      reoperation and elevated pulmonary artery pressure were associated with higher
      early mortality. The patients with decreased functional capacity (NYHA Class
      III/IV), congestive symptoms and rheumatic origin were more prone to low cardiac
      output development. The Kaplan-Meier survivals were 37% at 10 years and 30% at 15
      years. The 10-year event-free survival was 31%. Elevated pulmonary artery
      pressure and rheumatic etiology unfavorably affected the long-term results. The
      average functional capacity in survivors improved significantly after operation.
      CONCLUSIONS: Any tricuspid disease not amenable to repair thus necessitating
      replacement is an unfortunate situation since both the short and long-term
      results of valve replacement are suboptimal in regard to those of left-sided
      valve replacements, probably due to different structural and geometrical
      characteristics of right ventricle and the low-pressure venous system
      hemodynamics. Etiology, clinical presentation and pulmonary vascular hemodynamics
      are major determinants of the outcome.

PMID- 17555972
TI  - Mild and moderate renal dysfunction: impact on short-term outcome.
AB  - BACKGROUND: Preoperative renal dysfunction is an important risk factor in cardiac
      surgery. Thus, the association between creatinine clearance (ClCr) and mechanical
      ventilation time and ICU length of stay, independent of other established
      preoperative risk indicators, was analyzed. METHODS: In our study, 156
      consecutive patients underwent open-heart surgery at the Department of Cardiac
      Surgery, University Hospital St. Andrea, Rome, and were prospectively studied for
      the relation between the ClCr, using the formula develop by Cockroft and Gault,
      and ICU length of stay and mechanical ventilation time. The 156 patients were
      divided into two groups in relation of ClCr: group A (n=78) ClCr<70 ml/min; group
      B (n=78) ClCr>70 ml/min. RESULTS: In multivariate analysis, ICU length of stay
      was influenced by ClCr<70 ml/min, hypertension and COPD. ICU stay was median 48 h
      (range 24-72) in group A versus 24h (range 20.7-44) in group B (p=0.0001). In
      multivariate analysis, only ClCr<70 ml/min and EuroScore were associated with
      increasing VAM. VAM was median 8h (range 5.7-13.2) in group A versus 6h (range 4
      10) in group B (p=0.001). CONCLUSIONS: Our study demonstrates that after short
      term outcome follow-up, preoperative mild renal dysfunction is an independent
      predictor of ICU length of stay and mechanical ventilation time.

PMID- 17555973
TI  - Video-assisted left ventricle mass removal.

PMID- 17555974
TI  - Size matters in atrial fibrillation surgery.

PMID- 17555976
TI  - Compared fate of small-diameter Contegras and homografts in the pulmonary
      position.
AB  - OBJECTIVE: This study analyzes whether small-diameter Contegras behave in the
      same way as small-diameter homografts, when implanted for the first time in
      pulmonary position. METHODS: Small-diameter conduits include 12 and 14 mm
      Contegras and 8-14 mm homografts. Graft dysfunction is defined as right
      ventricular outflow tract obstruction with peak echo-Doppler gradient>40 mmHg, or
      grade III/IV graft regurgitation. Graft failure is defined as need for conduit
      replacement or need for catheter or surgical reintervention. Thirty-eight
      patients who received small Contegras (n=25) and small homografts (n=13) from
      October 2002 to end December 2006 were studied. The most frequent indication was
      pulmonary atresia and ventricular septal defect (n=20; 10 associated with major
      aorto-pulmonary collateral arteries), followed by truncus arteriosus (n=12). Most
      patients' characteristics were comparable except that recipients of homografts
      were smaller (p for body area=0.014). Survival, freedom from graft dysfunction,
      failure and explantation were estimated by the Kaplan-Meier method. The log-rank
      test was used to compare outcomes. RESULTS: There were three early and four late
      deaths. No death was graft related. Survival was 80+/-8.2% for patients with
      Contegras and 77+/-11.7% for those with allografts: p=0.82. Mean follow-up
      duration is 22+/-16 months. Freedom from dysfunction for Contegras conduits
      decreased in the first 6 months and stabilized at 58+/-11% from month 14. For
      homografts it decreased only 1 year after implantation, down to 35+/-19.7% from
      month 31: p=0.61. Freedom from Contegras failure diminished the first 16 months
      to level out at 57+/-13%. No homograft failed the first 2 years. With a p-value
      of 0.14, homografts tended to fail less frequently. Five grafts were explanted.
      Freedom from explantation was similar (p=0.98): 90+/-6.7% for Contegras and 75+/
      21.6% for homografts at year 3. CONCLUSION: In the first 4 years after pulmonary
      implantation of small-diameter Contegras and homografts, the fate of both
      conduits was statistically similar, in spite of different behavior. As Contegras
      is 'off-the-shelf' available, it constitutes a sound alternative to homograft for
      right ventricular outflow tract reconstruction in neonates and infants.

PMID- 17555977
TI  - Long-term survival after resection of giant chondrosarcoma of the chest wall
      weighing 9.6 kg.
AB  - The case of a 43 year old male with giant chest wall tumor weighing 9.6 kg
      verified as chondrosarcoma is described. The patient was treated by multiple (six
      times) surgical procedures including left costopleuropneumonectomy and left
      subclavian artery end-to-end anastomosis between 1998 and 2005. Despite the
      palliative character of surgery, he achieved long-term survival but finally
      refused next surgery due to the risk of left upper limb amputation and died a few
      months later.

PMID- 17555978
TI  - Lung cancer in octogenarians: factors affecting long-term survival following
      resection.
AB  - OBJECTIVE: To identify factors associated with long-term survival following
      pulmonary resection for lung cancer in patients 80 years of age or older.
      METHODS: The medical records of all patients >or=80 years, who underwent
      pulmonary resection for lung cancer from 1985 to 2002, were reviewed. RESULTS:
      There were 294 patients (192 men, 102 women). Median age was 82 years (range 80
      94 years). Overall 1-, 2-, and 5-year survival was 80%, 62%, and 34%,
      respectively. Histologic subtype, diabetes, renal insufficiency, prior myocardial
      infarction, congestive heart failure or stroke were not significantly associated
      with differences in 5-year survival. Female gender was associated with increased
      survival (36.2% vs 32.7% at 5 years, p=0.04). Extent of preoperative forced
      expiratory volume in 1s (FEV1) limitation did not influence survival. However,
      there were no 5-year survivors amongst patients with dyspnea as their presenting
      chief complaint, whereas there was a 35% 5-year survival in patients presenting
      without dyspnea (p<0.001). Five-year survival by pathologic stage was IA, 48%;
      IB, 39%; IIA, 17%; IIB, 23%; IIIA, 9%; and IIIB, 0% (p<0.001). Five-year survival
      of patients undergoing a lobectomy was 42% versus 11% for pneumonectomy
      (p<0.001). CONCLUSIONS: Meaningful long-term survival is obtainable in elderly
      patients undergoing surgical resection for lung cancer. Careful patient
      evaluation and selection is necessary to identify patients who will benefit most
      from resection. Shorter survival was observed in male patients and those
      presenting with dyspnea. As could be expected, survival was also dependent on
      extent of resection and initial pathologic stage.

PMID- 17555979
TI  - The impact of intraoperative transit time flow measurement on the results of on
      pump coronary surgery.
AB  - OBJECTIVE: The purpose of this study is to evaluate the effect of detection of
      graft dysfunction by intraoperative transit time flow measurement (TTFM) on the
      surgical results of on-pump coronary artery bypass grafting. METHODS: Two hundred
      patients undergoing on-pump isolate coronary artery bypass grafting via median
      sternotomy performed by the same surgical team were included into the study. TTFM
      was routinely performed for assessment of graft patency during operation after a
      transit time flow meter became available in our center in February 2006. The last
      100 consecutive patients before this date formed the control group (Group A), and
      the first 100 consecutive patients after this date formed the study group (Group
      B). Interpretation of the values obtained using the TTFM in Group B patients has
      allowed us to reach a decision whether or not to revise a graft. Preoperative and
      postoperative variables of the two groups were compared. RESULTS: The clinical
      features of control and study groups were comparable. We assessed patency of 303
      grafts using TTFM. Revision was required for nine grafts in nine patients based
      on unsatisfactory TTFM findings. Incidences of overall mortality (p<0.05), peri-
      or postoperative myocardial infarction (p<0.05) and intraaortic balloon pump
      insertion (p<0.05) were significantly lower in Group B than Group A. CONCLUSIONS:
      We believe that TTFM seems to be a crucial tool for deciding if a graft is well
      functioning or not, and it allows for improvement of graft failure during
      operation. Our results suggest that detection of graft dysfunction
      intraoperatively by TTFM improves the surgical outcome.

PMID- 17555980
TI  - The therapeutic effect of low-level laser on repair of osteochondral defects in
      rabbit knee.
AB  - INTRODUCTION: Low level laser therapy (LLLT) has been shown to enhance collagen
      production and wound healing but its effect on cartilage repair from
      biomechanical point of view is not known yet. The aim of present study was to
      evaluate the biomechanical behaviour of repairing osteochondral defect in rabbits
      which received a pulsed low-level gallium-arsenide (Ga-As) laser irradiation.
      MATERIALS AND METHODS: Osteochondral defects with 5mm diameter and 4mm in depth
      induced by drilling in right femoral patellar grooves of 41 adolescent male
      rabbits. They were divided into experimental and control groups. Experimental
      group received pulsed Ga-As (890nm) laser irradiation with energy density of
      4.8J/cm(2). The rabbits in control group received placebo LLLT with shut-down
      equipment. The control defects were allowed to heal spontaneously. Each group
      were divided into three subgroups: A, B and C. Subgroups A, B and C were
      sacrificed on 4, 8, and 16 weeks after surgery. The knee joint were removed, and
      the defects were examined biomechanically by in situ-indentation method. The
      thickness, instantaneous and equilibrium indentation stiffness was measured
      during the test. Data were analysed using ANOVA and independent sample t-test.
      RESULT: While no difference was observed in the repaired cartilage biomechanical
      properties among 4th, 8th, 16th weeks in study groups. The equilibrium
      indentation stiffness of experimental group was significantly higher in 8th week
      in comparison with control group. CONCLUSION: LLLT significantly enhances the
      stiffness of repairing tissue in the 8th week post injury in osteochondral
      defects in rabbits.

PMID- 17555981
TI  - Gene expression profiling in sarcomas.
AB  - Sarcomas are a heterogeneous group of malignant mesenchymal tumors of difficult
      classification. There is considerable variability in both histological appearance
      and responsiveness to therapy. Their overall poor clinical prognosis is reflected
      by the fact that >65% of patients suffering retroperitoneal soft tissue sarcoma
      die within 5 years [Heslin MJ, et al. Prognostic factors associated with long
      term survival for retroperitoneal sarcoma: implications for management. J Clin
      Oncol 1997;15(8):2832-9]. A greater understanding of the biology of sarcomas is
      needed in order to increase the potential for identifying new therapeutic targets
      and strategies. Microarray analysis permits a global approach to gene expression
      analysis of thousands of genes at the same time and has proven to be useful for
      further molecular characterization of tumor tissue and cell lines. This article
      provides a comprehensive review of possible new biomarkers identified in gene
      expression studies of sarcomas. These markers give new insight into the
      pathogenesis of sarcomas, such as malignant fibrous histiocytoma [Lee YF, et al.
      Molecular classification of synovial sarcomas, leiomyosarcomas and malignant
      fibrous histiocytomas by gene expression profiling. Br J Cancer 2003;88(4):510
      5], allow a further subclassifcation of tumors like calponin-positive and
      calponin-negative leiomyosarcoma, or may help to predict treatment responsiveness
      and prognosis in patients based on an individual gene expression pattern. In some
      studies candidate targets for possible new treatment strategies were identified.
      For instance newly identified markers such as ERBB2 [Allander SV, et al.
      Expression profiling of synovial sarcoma by cDNA microarrays: association of
      ERBB2, IGFBP2, and ELF3 with epithelial differentiation. Am J Pathol
      2002;161(5):1587-95] and EGFR [Nielsen TO, et al. Molecular characterization of
      soft tissue tumours: a gene expression study. Lancet 2002;359(9314):1301-7] might
      lead to the possible therapeutic use of Trastuzumab, Gefitinib or Cetuximab in
      synovial sarcoma, comparable to the use of tyrosine kinase inhibitor STI
      (Gleevec) that is the standard treatment today of CD117-positive gastrointestinal
      stromal tumors.

PMID- 17555982
TI  - Aromatic nucleophilic substitution (SNAr) reactions of 1,2- and 1,4
      halonitrobenzenes and 1,4-dinitrobenzene with carbanions in the gas phase.
AB  - In the gas-phase reactions of halonitro- and dinitrophenide anions with X (X = F,
      Cl, Br, NO(2)) and NO(2) groups in ortho or para position to each other with
      selected C-H acids: CH(3)CN, CH(3)COCH(3), and CH(3)NO(2), products of the S(N)Ar
      type reaction are formed. Nitrophenide anions are generated by decarboxylation of
      the respective nitrobenzenecarboxylate anions in ESI ion source and the S(N)Ar
      reaction takes place either in the medium-pressure zone of the ion source or in
      the collision chamber of the triple quadrupole mass spectrometer. In the case of
      F, Cl, and NO(2) derivatives, the main ionic product is the respective [NO(2)-Ph
      CHR](-) anion (R = CN, COCH(3), NO(2)). In the case of Br derivatives, the main
      ionic product is Br(-) ion because it has lower proton affinity than the [NO(2)
      Ph-CHR](-) anion (for R = CN, COCH(3)). For some halonitrophenide anion C-H acid
      pairs of reactants, the S(N)Ar reaction is competed by the formation of
      halophenolate anions. This reaction can be rationalized by the single electron
      transfer mechanism or by homolytic C-H bond cleavage in the proton-bound complex,
      both resulting in the formation of the halonitrobenzene radical anion, which in
      turn undergoes -NO(2) to -ONO rearrangement followed by the NO(.) elimination.

PMID- 17555983
TI  - Focus in honor of David E. Clemmer, recipient of the 2006 Biemann medal.

PMID- 17555984
TI  - Carbon stable isotope analyses of mosses--comparisons of bulk organic matter and
      extracted nitrocellulose.
AB  - The commonly used technique for determination of plant stable carbon isotope
      composition is analysis of CO(2) liberated during combustion of chemically
      extracted nitrocellulose or alpha-cellulose. The delta(13)C of cellulose is
      usually accepted as a more reliable record of growth environment conditions
      compared with bulk plant material analysis. Unfortunately, cellulose extraction
      techniques are time-consuming, and usually require toxic chemicals such as
      toluene, chloroform, benzene, methanol, concentrated acids, etc. We tested the
      possibility of replacing nitrocellulose analysis with bulk organic analysis.
      Sphagnum and Polytrichum mosses collected along a vertical transect (altitudes
      500 to 1400 m), provided material for analysis in the wide range of delta(13)C: 
      32.66 per thousand and -26.20 per thousand for bulk organic matter and -24.11 per
      thousand and -31.86 per thousand for nitrocellulose. The correlation for
      delta(13)C value of extracted cellulose and delta(13)C values of bulk organic
      matter were very good (>0.95). Our results suggested that delta(13)C analyses can
      be performed on bulk plant material instead of cellulose, without significant
      loss of information, at least for Polytrichum and Sphagnum mosses. Moreover, we
      confirmed that the extraction process of nitrocellulose did not cause any
      significant isotopic fractionation.

PMID- 17555986
TI  - Time-series analysis of meningococcal disease in Catalonia.
AB  - PURPOSE: In Catalonia, a region in the northeast of Spain, a rate of five cases
      of meningococcal disease per 100,000 inhabitants was reported during the period
      of 1996-1997, which was higher than in previous years. The objective of this
      study was to analyze the temporal behavior of serogroup B and C meningococcal
      disease cases in Catalonia. METHODS: The study included confirmed cases of
      meningococcal disease from the 4-week period 11 of 1996 to the 4-week period 10
      of 2004. A Poisson regression model (GLM) was fit for time series of serogroup B
      cases, whereas a zero-inflated Poisson model (ZIP) was necessary to adjust time
      series of serogroup C cases. RESULTS: The evolution of cases in both serogroups
      was correlated over time. For serogroup B, there was also an association with the
      influenza epidemics reported in four of the seasons analyzed. For serogroup C, a
      positive association with three influenza epidemics and a negative association
      with vaccination campaigns were found. Time series analysis of meningococcal
      disease shows that serogroups B and C behave in a different way. CONCLUSIONS: The
      study of the evolution of each serogroup may be useful in evaluating vaccination
      strategies.

PMID- 17555985
TI  - Dietary histone deacetylase inhibitors: from cells to mice to man.
AB  - Sulforaphane (SFN) is an isothiocyanate found in cruciferous vegetables, such as
      broccoli and broccoli sprouts. This anticarcinogen was first identified as a
      potent inducer of Phase 2 detoxification enzymes, but evidence is mounting that
      SFN also acts through epigenetic mechanisms. SFN has been shown to inhibit
      histone deacetylase (HDAC) activity in human colon and prostate cancer lines,
      with an increase in global and local histone acetylation status, such as on the
      promoter regions of P21 and bax genes. SFN also inhibited the growth of prostate
      cancer xenografts and spontaneous intestinal polyps in mouse models, with
      evidence for altered histone acetylation and HDAC activities in vivo. In human
      subjects, a single ingestion of 68 g broccoli sprouts inhibited HDAC activity in
      circulating peripheral blood mononuclear cells 3-6 h after consumption, with
      concomitant induction of histone H3 and H4 acetylation. These findings provide
      evidence that one mechanism of cancer chemoprevention by SFN is via epigenetic
      changes associated with inhibition of HDAC activity. Other dietary agents such as
      butyrate, biotin, lipoic acid, garlic organosulfur compounds, and metabolites of
      vitamin E have structural features compatible with HDAC inhibition. The ability
      of dietary compounds to de-repress epigenetically silenced genes in cancer cells,
      and to activate these genes in normal cells, has important implications for
      cancer prevention and therapy. In a broader context, there is growing interest in
      dietary HDAC inhibitors and their impact on epigenetic mechanisms affecting other
      chronic conditions, such as cardiovascular disease, neurodegeneration and aging.

PMID- 17555988
TI  - Correlation of quantitative MRI and neuropathology in epilepsy surgical resection
      specimens--T2 correlates with neuronal tissue in gray matter.
AB  - Newer MRI methods can detect cerebral abnormalities not identified on routine
      imaging in patients with focal epilepsy. Correlation of MRI with histopathology
      is necessary to understand the basis of MRI abnormalities and subsequently
      predict histopathology from in vivo MRI. The aim of this study was to determine
      if particular quantitative MR parameters were associated with particular
      histological features. Nine patients with temporal lobe epilepsy were imaged at
      1.5 T using standard presurgical volumetric and quantifiable sequences:
      magnetization transfer and FFT2. The resected temporal lobe was registered with
      the volumetric MRI data according to our previously described method to permit
      correlation of the modalities. Stereologically measured neuronal densities and
      field fraction of GFAP, MAP2, synaptophysin and NeuN immunohistochemistry were
      obtained. Analyses were performed in the middle temporal gyrus and compared with
      quantitative MRI data from the equivalent regions. There was a significant
      Spearman Rho negative correlation between NeuN field fraction and the T2 value in
      gray matter (correlation coefficient -0.72, p=0.028). There were no significant
      correlations between any neuropathological and MR measures in white matter. These
      preliminary findings suggest that T2 in gray matter is sensitive to the
      proportion of neuronal tissue. Novel quantitative MRI measures acquired with
      higher field strength magnets, and so with superior signal to noise ratios, may
      generate data that correlate with histopathological measures. This will enable
      better identification and delineation of the structural causes of refractory
      focal epilepsy, and will be of particular benefit in patients in whom current
      optimal MRI does not identify a relevant abnormality.

PMID- 17555989
TI  - Working memory effects on semantic processing: priming differences in pars
      orbitalis.
AB  - Both working memory (WM) and controlled (attention-mediated) semantic processing
      functions have been thought to operate as limited capacity systems, but the
      possible link between these processes has not been investigated. We found that
      increased WM load attenuated semantic priming (i.e., reduced the response time
      advantage for semantically primed relative to unprimed items) and changed fMRI
      signal intensities in brain regions usually associated with both WM (dorsolateral
      prefrontal cortex) and controlled semantic retrieval (inferior frontal gyrus
      [IFG], pars orbitalis). fMRI signal changes in dorsolateral prefrontal cortex
      were negatively correlated with signal changes in pars orbitalis. The findings
      suggest that controlled semantic processing and working memory share neural
      system resources.

PMID- 17555990
TI  - A multi-gene phylogeny of Clavicipitaceae (Ascomycota, Fungi): identification of
      localized incongruence using a combinational bootstrap approach.
AB  - Multi-gene phylogenetic analyses were conducted to address the evolution of
      Clavicipitaceae (Ascomycota). Data are presented here for approximately 5900 base
      pairs from portions of seven loci: the nuclear ribosomal small and large subunit
      DNA (nrSSU and nrLSU), beta-tubulin, elongation factor 1alpha (EF-1alpha), the
      largest and second largest subunits of RNA polymerase II (RPB1 and RPB2), and
      mitochondrial ATP Synthase subunit 6 (mtATP6). These data were analyzed in a
      complete 66-taxon matrix and 91-taxon supermatrix that included some missing
      data. Separate phylogenetic analyses, with data partitioned according to genes,
      produced some conflicting results. The results of separate analyses from RPB1 and
      RPB2 are in agreement with the combined analyses that resolve a paraphyletic
      Clavicipitaceae comprising three well-supported clades (i.e., Clavicipitaceae
      clade A, B, and C), whereas the tree obtained from mtATP6 is in strong conflict
      with the monophyly of Clavicipitaceae clade B and the sister-group relationship
      of Hypocreaceae and Clavicipitaceae clade C. The distribution of relative
      contribution of nodal support for each gene partition was assessed using both
      partitioned Bremer support (PBS) values and combinational bootstrap (CB)
      analyses, the latter of which analyzed bootstrap proportions from all possible
      combinations of the seven gene partitions. These results suggest that CB analyses
      provide a more consistent estimate of nodal support than PBS and that combining
      heterogeneous gene partitions, which individually support a limited number of
      nodes, results in increased support for overall tree topology. Analyses of the 91
      taxa supermatrix data sets revealed that some nodes were more strongly supported
      by increased taxon sampling. Identifying the localized incongruence of mtATP6 and
      analyses of complete and supermatrix data sets strengthen the evidence for
      rejecting the monophyly of Clavicipitaceae and much of the current subfamilial
      classification of the family. Although the monophyly of the grass-associated
      subfamily Clavicipitoideae (e.g., Claviceps, Balansia, and Epichloe) is strongly
      supported, the subfamily Cordycipitoideae (e.g., Cordyceps and Torrubiella) is
      not monophyletic. In particular, species of the genus Cordyceps, which are
      pathogens of arthropods and truffles, are found in all three clavicipitaceous
      clades. These results imply that most characters used in the current familial
      classification of Clavicipitaceae are not diagnostic of monophyly.

PMID- 17555991
TI  - Initial T cell receptor transgenic cell precursor frequency dictates critical
      aspects of the CD8(+) T cell response to infection.
AB  - Adoptive-transfer experiments with relatively large input numbers ( approximately
      10(6)) of T cell receptor-transgenic (TCR-tg) T cells are widely used to model
      endogenous T cell responses to infection or immunization. We show that input
      numbers of naive TCR-tg T cells sufficient to squelch the endogenous response to
      the same epitope substantially alter the kinetics, proliferative expansion,
      phenotype, and efficiency of memory generation by the TCR-tg T cells in response
      to infection. Thus, responses from nonphysiologic input numbers of TCR-tg T cells
      fail to accurately mimic the endogenous T cell response. Importantly, seeding as
      few as approximately 10-50 TCR-tg T cells, which constitute a fraction of the
      endogenous repertoire, allowed vigorous proliferation and analysis of TCR-tg
      cells after infection in a scenario representing normal physiology for any
      individual TCR. These data strongly suggest that modeling the endogenous T cell
      response with TCR-tg cells will require every effort to approximate the
      endogenous precursor frequency.

PMID- 17555992
TI  - Ablation of ribosomal protein L22 selectively impairs alphabeta T cell
      development by activation of a p53-dependent checkpoint.
AB  - The alphabeta and gammadelta T lineages are thought to arise from a common
      precursor; however, the regulation of separation and development of these
      lineages is not fully understood. We report here that development of alphabeta
      and gammadelta precursors was differentially affected by elimination of ribosomal
      protein L22 (Rpl22), which is ubiquitously expressed but not essential for
      translation. Rpl22 deficiency selectively arrested development of alphabeta
      lineage T cells at the beta-selection checkpoint by inducing their death. The
      death was caused by induction of p53 expression, because p53 deficiency blocked
      death and restored development of Rpl22-deficient thymocytes. Importantly, Rpl22
      deficiency led to selective upregulation of p53 in alphabeta-lineage thymocytes,
      at least in part by increasing p53 synthesis. Taken together, these data indicate
      that Rpl22 deficiency activated a p53-dependent checkpoint that produced a
      remarkably selective block in alphabeta T cell development but spared gammadelta
      lineage cells, suggesting that some ribosomal proteins may perform cell-type
      specific or stage-specific functions.

PMID- 17555993
TI  - A-to-I RNA editing: a new regulatory mechanism of global gene expression.
AB  - The complexity of higher organisms is based on the number of different gene
      products available for structural, regulatory and enzymatic regulatory functions
      and the precise and coordinated control of gene expression. A-to-I RNA editing
      emerges as a global post-transcriptional modification that affects thousands of
      transcripts. RNA editing is becoming a central modification acting on double
      stranded RNA and is therefore intimately associated with other basic processes
      such as RNA interference, microRNA and interferon response that also depend on
      double-stranded RNA. Recent research highlights the multiple roles of this
      mechanism in the transcriptome diversification and in the special and temporal
      gene expression control. Alterations in A-to-I RNA editing have now been linked
      to various human diseases. The increased understanding of the editing machinery
      and identification of the multiple targets are expected to improve our
      understanding of the roles of this mechanism in normal development and
      homeostasis and its derangement in disease states. Basic and translational
      research is expected to increase our understanding of this intriguing mechanism
      which is endowed with diagnostic and therapeutic implications.

PMID- 17555994
TI  - Gene expression shifts during perithecium development in Gibberella zeae
      (anamorph Fusarium graminearum), with particular emphasis on ion transport
      proteins.
AB  - Gibberella zeae, the causal agent of Fusarium head blight, is a devastating
      pathogen of small grains worldwide. The sexual cycle is a crucial component of
      head blight epidemiology, as forcibly discharged ascospores serve as the primary
      inoculum. The recent development of an Affymetrix GeneChip containing probesets
      representative of all predicted genes of G. zeae has opened the door to studies
      of differential gene expression during sexual development. Using GeneChips, a
      developmental time course was performed in culture, from vegetative hyphae to
      mature perithecia with multiseptate ascospores. Time-points represent the
      development of the major cell types comprising the mature perithecium. The
      majority of the 17,830 G. zeae probesets, 78%, were expressed during at least one
      of the developmental stages; 12% of these appear to be specific to sexual
      development. Analysis of the 162 predicted ion transporter genes is reported in
      detail, due to their association with perithecium function. Expression patterns
      of the MirA-type siderophores, chloride channels, P-type ATPases and potassium
      transporters show some specialization in regard to developmental stage. This is
      the first whole-genome analysis of differential transcript accumulation during
      sexual development in a filamentous fungus.

PMID- 17555995
TI  - Pulmonary oedema as a suspected adverse drug reaction following vincristine
      administration to a cat: a case report.
AB  - This report describes recurrent respiratory distress following vincristine
      administration to a cat with chronic lymphocytic leukaemia. The cat was treated
      with a combination of vincristine, chlorambucil and prednisolone with initial
      success. After approximately 4 months, dyspnoea developed within 6 h of
      vincristine administration. Emergency therapy was instituted resulting in a full
      recovery. Further vincristine was administered; dyspnoea was similarly noted
      after all but one of these treatments. Dyspnoeic episodes were not attributable
      to alterations in vincristine dose or method of administration. The repeated
      temporal association was consistent with a suspected adverse drug reaction to
      vincristine.

PMID- 17555996
TI  - Molecular detection of a Hepatozoon species in stray cats from a feline colony in
      North-eastern Spain.
AB  - Within the framework of a local animal health programme, the presence of
      ectoparasites and haemoparasites was investigated in a colony of 25 cats in
      Barcelona. Diagnosis was performed both by standard parasitological procedures
      and molecular techniques. All cats were negative to haematozoan infection by
      microscopic examination of blood smears. However, Hepatozoon spp. was found in
      four cats as shown by amplification and sequencing of the 18S rRNA gene. Cat
      isolates were 100% identical to the isolate Hepatozoon spp. (Spain 2) from
      Southern Spain. This is the first time that Hepatozoon spp. has been identified
      in cats from Northern Spain.

PMID- 17555997
TI  - Comparison of metabolic rates and feed nutrient digestibility in conventional,
      genetically improved (GIFT) and genetically male (GMNT) Nile tilapia, Oreochromis
      niloticus (L.).
AB  - Various aspects of energy metabolism and feed digestibility were evaluated in two
      reportedly improved strains of Nile tilapia (Oreochromis niloticus) namely GIFT
      (genetically improved farmed tilapia) and GMNT (genetically male Nile tilapia)
      and compared with those of CNT (conventional Nile tilapia). Fish were stocked
      individually in a computer-controlled respirometer system at 27+/-0.1 degrees C
      for 10 weeks. Metabolic rates were measured at three different feeding levels:
      starved, maintenance (3.0 g kg(-0.8) day(-1)) and growth (7.5 g kg(-0.8) day(-1))
      using a fishmeal based feed containing TiO2 marker (41% crude protein, 9% crude
      lipid and 19 kJ (g DM)(-1) gross energy). The standard metabolic rate (SMR),
      measured at the beginning of the experiment (45.4+/-4.6, 52.4+/-7.7 and 46.8+/
      4.6 mg O2 kg(-0.8) h(-1) respectively for GIFT, GMNT and CNT), did not differ
      significantly between the groups (p<0.05). Similarly, non-significant differences
      were also observed in the routine metabolic rates under starved, maintenance and
      growth conditions but the variability was higher in the case of GMNT and CNT than
      in GIFT. The latter group showed a significantly lower active metabolic rate (145
      mg O2 kg(-0.8) h(-1)) compared to GMNT and CNT (232 and 253 mg O2 kg(-0.8) h(-1),
      respectively) at maintenance feeding level. The specific dynamic action (%
      offered feed energy) showed no significant differences among the groups.
      Digestibility coefficients of feed dry matter, protein, lipid and energy for the
      three tilapia groups also did not differ significantly. Therefore, we concluded
      that the genetic improvement or modification in the GIFT or GMNT might not
      upgrade the inherent physiological potential compared to CNT as far as energy
      metabolism and digestion efficiencies are concerned.

PMID- 17555998
TI  - Molecular cloning and expression analysis of ecdysone receptor and retinoid X
      receptor from the kuruma prawn, Marsupenaeus japonicus.
AB  - Two cDNAs encoding EcR (MjEcR) and RXR (MjRXR) were cloned and sequenced from the
      kuruma prawn Marsupenaeus japonicus using PCR techniques. The amino acid sequence
      of MjEcR was similar to that of known EcR especially in the ligand binding domain
      (LBD) of insect EcR. The DNA binding domain of MjRXR showed higher homology with
      that of insect USP (>90% identity) than vertebrate RXR ( approximately 85%
      identity), while LBD of MjRXR is more homologous with that of vertebrate RXR (
      approximately 65% identity) than that of insect USP (30-60% identity). The
      transcripts of MjEcR and MjRXR were expressed in all tissues examined and in
      particular, highly in Y-organ and heart and in ovary and heart, respectively.
      Quantitative real-time PCR analyses revealed that the expression level of MjEcR
      in hepatopancreas and thoracic muscle increased from intermolt to premolt stages.
      The analyses also showed that the expressions of MjEcR and MjRXR were regulated
      in a tissue-specific manner. No significant changes were observed in reproductive
      organs throughout the molting stages, and MjRXR was expressed much more than
      MjEcR at all stages. These data suggest that MjRXR mediates a certain hormonal
      signal related to reproduction.

PMID- 17555999
TI  - A SNP haplotype of the forkhead transcription factor FOXO1A gene may have a
      protective effect against type 2 diabetes in German Caucasians.
AB  - AIM: The human protein encoded by the FOXO1A gene functions as a transcription
      factor of insulin signaling key genes. In this study we investigated the role of
      genetic variation in the FOXO1A gene in susceptibility to type 2 diabetes (T2D)
      and relevant metabolic traits. METHODS: We genotyped six haplotype tagging single
      nucleotide polymorphisms (SNPs) for association analyses in German Caucasians
      (593 patients with T2D and 760 non-diabetics, who included 594 normoglycemics and
      166 individuals with impaired glucose tolerance). RESULTS: In a case control
      study involving all type 2 diabetics and healthy controls with normal glucose
      tolerance, none of the FOXO1A SNPs showed any association with T2D. However, the
      frequency of the [C-C-G-A-A-A] haplotype comprising six FOXO1A SNPs was 36.5% in
      normoglycemic non-diabetic controls compared to 31.0% in type 2 diabetic patients
      (P=0.004). Consistent with this, the same haplotype was significantly associated
      with lower fasting plasma insulin, BMI, HbA(1C), free fatty acids and % body fat
      in all non-diabetic subjects (all adjusted P<0.05). CONCLUSION: In conclusion,
      our study suggests a protective effect of FOXO1A haplotype [C-C-G-A-A-A] on T2D
      development and relevant intermediate phenotypes which predispose for T2D.

PMID- 17556000
TI  - [Numerical variants and congenital fusions of carpal bones].
AB  - The number of carpal bones may be increased or decreased by the fact of
      anatomical variants or true congenital anomalies. Numerical increment arises from
      additional or from split bones. Over twenty accessory carpal bones have been
      described but the commonest are the os centrale carpi, the os radiale externum,
      the triangular bone and the styloideum bone. Additional carpal bones usually
      result from a failure of fusion of their ossification centers. A congenital
      origin is not clearly established for all these ossicles. The scaphoid and lunate
      may split into two or three bones and several cases of bipartite hamulus of the
      hamatum have been reported. A carpus with only seven bones results from the
      congenital absence of a normal bone, which mainly affects the scaphoid, lunate
      and triquetrum, or from a synostosis between two carpal bones, usually the lunate
      and triquetrum. Congenital fusions originate from an absence of joint cavitation
      into the embryo and chondrification of the joint interzone. Numerical carpal
      variants are uncommon as independent entities but occur with a relative high
      frequency in association with complex malformations of the hand. These anomalies
      are detectable on plain radiographs of the wrist, but CT-scan and MR-Imaging are
      useful to differentiate bipartite and accessory bones from carpal fractures or
      posttraumatic injuries, carpal fusions having to be distinguished from bony
      ankylosis.

PMID- 17556001
TI  - In vitro infection of human dendritic cells by Aspergillus fumigatus conidia
      triggers the secretion of chemokines for neutrophil and Th1 lymphocyte
      recruitment.
AB  - Given the role played by chemokines in the selective homing of immune cells, we
      sought to characterize the profile of chemokines produced by human dendritic
      cells (DC) following in vitro Aspergillus fumigatus infection and their ability
      to recruit cells involved in the antifungal defense. At the onset of A. fumigatus
      infection, DC released elevated amounts of CXCL8 that promote the migration of
      polymorphonuclear cells (PMN). Moreover, soluble factors released from A.
      fumigatus-infected DC increased also the surface expression of two activation
      markers, CD11b and CD18, on PMN. A. fumigatus infection resulted also in CCL3,
      CCL4, CXCL10 and CCL20 productions that induce the migration of effector memory
      Th1 cells. Moreover, the late expression of CCL19 suggests that A. fumigatus
      infected DC could be implicated in the migration of CCR7+ naive T cells and
      mature DC in lymph nodes. Together these results suggested the involvement of
      human DC in the regulation of innate and adaptive immunity against A. fumigatus
      through the recruitment of cells active in the fungal destruction.

PMID- 17556002
TI  - Phytomonas serpens: immunological similarities with the human trypanosomatid
      pathogens.
AB  - The present review provides an overview of recent discoveries concerning the
      immunological similarities between Phytomonas serpens, a tomato parasite, and
      human trypanosomatid pathogens, with special emphasis on peptidases. Leishmania
      spp. and Trypanosoma cruzi express peptidases that are well-known virulence
      factors, named leishmanolysin and cruzipain. P. serpens synthesizes two distinct
      classes of proteolytic enzymes, metallo- and cysteine-type peptidases, that share
      common epitopes with leishmanolysin and cruzipain, respectively. The
      leishmanolysin-like and cruzipain-like molecules from P. serpens participate in
      several biological processes including cellular growth and adhesion to the
      salivary glands of Oncopeltus fasciatus, a phytophagous insect experimental
      model. Since previous reports demonstrated that immunization of mice with P.
      serpens induced a partial protective immune response against T. cruzi, this plant
      trypanosomatid may be a suitable candidate for vaccine studies. Moreover,
      comparative approaches in the Trypanosomatidae family may be useful to understand
      kinetoplastid biology, biochemistry and evolution.

PMID- 17556003
TI  - The weak interaction of LcrV and TLR2 does not contribute to the virulence of
      Yersinia pestis.
AB  - Yersinia pestis and the enteropathogenic Yersinia pseudotuberculosis and Yersinia
      enterocolitica share the virulence-antigen LcrV. Previously, using reverse
      genetics we have proven that LcrV contributes to the virulence of Y.
      enterocolitica serotype O:8 by inducing IL-10 via Toll-like receptor 2 (TLR2).
      However, both the ability of Y. pestis LcrV to activate TLR2 and a possible role
      of TLR2-dependent IL-10 induction by LcrV in Y. pestis are not yet known. To
      eliminate interference from additional protein sequences, we produced LcrVs
      without affinity tags from Y. pestis and from Y. enterocolitica O:8 (LcrVO:8).
      LcrVO:8 was much more potent in TLR2-activity than Y. pestis LcrV. To analyse the
      role of TLR2 in plague, we infected both wild-type and TLR2-/- mice
      subcutaneously with Y. pestis GB. While TLR2-/- mice exhibited lower blood levels
      of IL-10 (day 2 post-infection) and of the pro-inflammatory cytokines TNF-alpha,
      IFN-gamma and MCP-1 (day 4) than wild-type mice, there was no significant
      difference in survival. The low TLR2-activity of Y. pestis LcrV and associated
      cytokine expression might explain why - in contrast to Y. enterocolitica O:8
      infection - TLR2-deficient mice are not more resistant than wild-type mice in a
      bubonic plague model.

PMID- 17556004
TI  - A novel automatic image processing algorithm for detection of hard exudates based
      on retinal image analysis.
AB  - We present an automatic image processing algorithm to detect hard exudates.
      Automatic detection of hard exudates from retinal images is an important problem
      since hard exudates are associated with diabetic retinopathy and have been found
      to be one of the most prevalent earliest signs of retinopathy. The algorithm is
      based on Fisher's linear discriminant analysis and makes use of colour
      information to perform the classification of retinal exudates. We prospectively
      assessed the algorithm performance using a database containing 58 retinal images
      with variable colour, brightness, and quality. Our proposed algorithm obtained a
      sensitivity of 88% with a mean number of 4.83+/-4.64 false positives per image
      using the lesion-based performance evaluation criterion, and achieved an image
      based classification accuracy of 100% (sensitivity of 100% and specificity of
      100%).

PMID- 17556005
TI  - Blood flow dynamics in patient-specific cerebral aneurysm models: the
      relationship between wall shear stress and aneurysm area index.
AB  - Hemodynamics plays an important role in the progression and rupture of cerebral
      aneurysms. The temporal and spatial variations in wall shear stress (WSS) within
      the aneurysmal sac are hypothesized to be correlated with the growth and rupture
      of the aneurysm. The current work describes the blood flow dynamics in 34 patient
      specific models of saccular aneurysms located in the region of the anterior and
      posterior circulation of the circle of Willis. The models were obtained from
      three-dimensional rotational angiography image data and blood flow dynamics was
      studied under a physiologically representative waveform of inflow. The three
      dimensional continuity and momentum equations for unsteady laminar flow were
      solved with commercial software using non-structured fine grid sizes. The vortex
      structure, the wall pressure, and the WSS showed large variations, depending on
      the morphology of the artery, size of the aneurysm, and form. A correlation
      existed between the mean WSS on the aneurysmal sac for lateral unruptured and
      ruptured aneurysms with an aneurysm surface index, which is defined as the ratio
      between the aneurysm area and the artery area at model inlet, respectively.

PMID- 17556006
TI  - The reliability of paraspinal muscles composition measurements using routine
      spine MRI and their association with back function.
AB  - This study examines the reliability of quantitative and qualitative muscle
      composition measurements of paraspinal muscle cross-sectional areas (CSAs) from
      routine lumbar spine magnetic resonance images and their association with maximal
      isokinetic lifting performance. The extent of paraspinal muscle composition
      reflects back function is currently not known. Measurements were repeated 4-8
      weeks apart and different measurements of related constructs were compared.
      Participants were a population-based sample of 169 males, 35-67 years old,
      without considering the presence or absence of a history of low back pain or
      related problems in the selection of subjects. The quantitative and qualitative
      muscle composition measurements for axial magnetic resonance (MR) images of
      paraspinal muscles at the L3-L4 lumbar spine level, isokinetic lifting force and
      work, and body fat percentage were the main outcome measures. Results showed that
      the reproducibility of different paraspinal muscle composition measurements at
      the L3-L4 level was excellent for CSAs (ICC=0.95-0.99) and quantitative muscle
      composition measurements using cerebrospinal fluid adjusted signal intensity
      (ICC=0.96-0.99), and moderate for qualitative muscle composition ratings
      (Kappa=0.54-0.76). The correlations of the quantitative and qualitative muscle
      composition measurements with isokinetic lifting force and work were generally
      low (r=0.02-0.41), and favoured the qualitative assessments. In conclusion,
      quantitative and qualitative muscle composition measurements of paraspinal
      muscles are highly reproducible tissue measures, have low associations with body
      fat and isokinetic lifting performance, and show that paraspinal muscle
      morphology using routine spine magnetic resonance imaging (MRI) is poorly related
      to back function.

PMID- 17556007
TI  - Alterations of stiffness and resting position of the elbow joint following
      flexors resistance training.
AB  - Skeletal muscles adapt their length and stiffness according to the functional
      demands to which they are regularly submitted. The modification of muscle
      stiffness and length induced by resistance training can alter joint stiffness
      and, theoretically, change joint resting position. Thirty subjects, randomly
      assigned to two groups, were submitted to a resistance training of the elbow
      flexor muscles of the non-dominant arm. This training was performed in the inner
      range in group 1 and throughout the complete range of motion in group 2. The
      dominant arm of each subject was considered the control. A biomechanical model of
      a hybrid mass-spring pendulum was used to estimate the elbow joint stiffness and
      the elbow resting position was assessed using a standard goniometer. There was a
      significant increase in joint stiffness of the experimental arm after complete
      range of motion training, which was not observed after the training performed in
      inner range. The resting position of the experimental arm was modified to a
      significantly greater flexion angle in both groups. No change was observed after
      resistance training in the control arm. The results showed that modifications in
      joint stiffness seem to depend on the volume of work imposed to skeletal muscles.
      In addition, both models of resistance training changed, through different
      mechanisms, the elbow joint resting position. These findings suggest that posture
      and joint stability may be modified by specific strengthening protocols.

PMID- 17556008
TI  - Identification of BARD1 splice-isoforms involved in human trophoblast invasion.
AB  - The tumor suppressor protein BARD1, originally discovered as BRCA1-binding
      protein, acts in conjunction with BRCA1 as ubiquitin ligase. BARD1 and BRCA1 form
      a stable heterodimer and dimerization, which is required for most tumor
      suppressor functions attributed to BRCA1. In addition, BARD1 has BRCA1
      independent functions in apoptosis, and a role in control of tissue homeostasis
      was suggested. However, cancer-associated mutations of BARD1 are rare; on the
      contrary, overexpression of truncated BARD1 was found in breast and ovarian
      cancer and correlated with poor prognosis. Here we report that human
      cytotrophoblasts, which show a strong similarity with cancer cells in respect of
      their invasive behavior and capacity of matrix metalloprotease production,
      overexpress isoforms of BARD1 derived from differential splicing. We demonstrate
      that expression of BARD1 and its isoforms is temporally and spatially regulated
      by human chorionic gonadotropin and by hypoxia, both factors known to regulate
      the invasive phase and proliferation of cytotrophoblasts. Interestingly, we found
      a subset of BARD1 isoforms secreted by cytotrophoblasts. BARD1 repression by
      siRNAs, mitigates the interference of cytotrophoblasts with cell adhesion of
      collagen matrix-dependent epithelial cells, suggesting a role of BARD1 isoforms
      in extracellular matrix remodelling and in cytotrophoblasts invasion.

PMID- 17556010
TI  - Overexpression of fucosyltransferase IV in A431 cell line increases cell
      proliferation.
AB  - Fucosyltransferase IV is an essential enzyme that catalyzes the synthesis of
      fucosylated oligosaccharides by transferring GDP-fucose to the terminal N
      acetylglucosamine with the alpha1,3-linkage. Lewis Y oligosaccharide has a
      terminal alpha1,3-linked fucose residue and elevation of Lewis Y level is seen in
      many epithelial cancers. The mechanism of Lewis Y elevation in neoplastic cells
      is still largely unknown. To study the impact of fucosyltransferase IV on Lewis Y
      expression and its role on neoplastic cell proliferation, a pEGFP-N1-FUT4
      recombinant plasmid was developed and stably transfected into A431 cells. We
      found that fucosyltransferase IV overexpression promoted cell proliferation and
      increased the expression of proliferating cell nuclear antigen that correlated
      with Lewis Y augmentation. Cell cycle analysis demonstrated that
      fucosyltransferase IV overexpression facilitated cell cycle progression. In
      conclusion, fucosyltransferase IV overexpression augments Lewis Y expression to
      trigger neoplastic cell proliferation. These studies suggest that
      fucosyltransferase IV may serve as a potential therapeutic target for the
      treatment of Lewis Y-positive epithelial cancers.

PMID- 17556009
TI  - Tracking the fate of iron in early development of human blood flukes.
AB  - Iron (Fe) is an important trace element found in nearly all organisms, and is
      used as a cofactor in many biological reactions. One role for Fe in some
      invertebrates is in stabilization of extracellular matrices. The human blood
      fluke, Schistosoma japonicum, is responsible for significant human disease in
      developing and tropical nations. Disease in humans arises from host immunological
      reaction to parasite eggs that lodge in tissues. Schistosomes require Fe for
      development in their hosts, and store abundant Fe in vitelline (eggshell-forming)
      cells of the female system. The understanding of Fe metabolism and functionality
      are aspects of its biology that may be exploited in future therapeutics. The
      biology of Fe stores in vitelline cells of S. japonicum was investigated to
      illuminate possible functions of this element in early development of these
      parasites. Vitelline Fe is stored in yolk ferritin that is upregulated in females
      and is also expressed at low levels in egg-stages and adult males. Laser
      microdissection microscopy, coupled with reverse transcriptase- and real time-PCR
      amplification of schistosome ferritin sequences, confirmed that the vitelline
      cells are the likely progenitor cells of yolk ferritin. Assessment of Fe
      concentrations in whole male and whole female adult worms, eggs and purified
      eggshells by colorimetric assays and mass spectroscopy demonstrated higher levels
      of Fe in the female parasite, but also high levels of the element in whole
      parasite eggs and purified eggshell. Qualitative energy dispersive spectroscopy
      of purified eggshells, revealed that Fe is abundant in the eggshell, the matrix
      of which is composed of heavily cross-linked eggshell precursor proteins. Thus,
      vitelline stores of Fe are implicated in eggshell cross-linking in
      platyhelminths. These observations emphasise the importance of Fe in schistosome
      metabolism and egg formation and suggest new avenues for disruption of egg
      formation in these pathogenic parasites.

PMID- 17556011
TI  - Sensitivity of the brain to loss aversion during risky gambles.
AB  - Little is known about the neural systems that subserve human loss aversion. A
      recent neuroimaging study by Tom, Poldrack and colleagues reports that this
      pattern of behaviour is directly tied to the greater sensitivity of the brain to
      potential losses compared with potential gains and uncovers a brain network whose
      activity increases with potential gains and decreases with potential losses.
      These results challenge the common view that loss aversion engages a distinct
      emotion-related brain network (e.g. amygdala and insula).

PMID- 17556012
TI  - Effects of cadmium on root apical meristems of Pisum sativum L.: cell viability,
      cell proliferation and microtubule pattern as suitable markers for assessment of
      stress pollution.
AB  - By studying the effects of four concentrations of cadmium (0.25, 2.5, 25,
      250microM) on Pisum sativum L. roots, we compared parameters generally used in
      short-term tests for environmental monitoring - root length, mitotic index,
      occurrence of mitotic aberrations - with less explored parameters related to
      meristem activity, such as apex size and viability, percentage of DNA
      synthesizing cells and microtubule alterations. The results show that low cadmium
      concentrations caused a reduction of root growth, which is directly related to
      reduction of apex length, mitotic activity and percentage of DNA-synthetizing
      cells. The microtubular cytoskeleton was highly sensitive to cadmium, as
      microtubule alterations appeared after treatment with the lowest cadmium
      concentration, pointing to microtubules or microtubule-associated proteins, among
      the main targets of cadmium. In contrast, cell viability was a less sensitive
      parameter, as it decreased only upon treatment with the highest cadmium
      concentrations. The different sensitivities of the parameters examined in this
      work support the use of different endpoints for assessment of risk from polluted
      soils and waters.

PMID- 17556013
TI  - Theoretical investigations of the EPR parameters for Cr3+ and Mn4+ ions in PbTiO3
      crystals.
AB  - The complete high-order perturbation formulas of EPR parameters (g factors g(
      parallel), g( perpendicular) and zero-field splitting D), containing the crystal
      field (CF) mechanism and charge-transfer (CT) mechanism (the latter is omitted in
      crystal-field theory which is often used to study the EPR parameters), are
      established from a cluster approach for 3d3 ions in tetragonal octahedral sites.
      According to the calculations based on these formulas, the EPR parameters g(
      parallel), g( perpendicular) and zero-field splitting D for Cr3+ and Mn4+ ions in
      PbTiO3 crystals are explained reasonably. The calculations show that (i) the sign
      of g-shift Deltag(i)(CT) (=g(i)-g(s), where g(s)=2.0023 is free-electron value
      and i= parallel and perpendicular) in CT mechanism is opposite to, but that of
      D(CT) is the same as, the corresponding signs in the CF mechanism and (ii) the
      relative importance of CT mechanism for the high valence state 3d3 ion (e.g.,
      Mn4+) is large and so the contributions to EPR parameters from CT mechanism
      should be taken into account. The different sign of splitting D and the different
      defect structure for Cr3+ and Mn4+ impurity centers in PbTiO3 crystals are also
      suggested from the calculations. The results are discussed.

PMID- 17556014
TI  - Distributed cognition: an alternative model of cognition for medical informatics.
AB  - BACKGROUND: Medical informatics has been guided by an individual-centered model
      of human cognition, inherited from classical theory of mind, in which knowledge,
      problem-solving, and information-processing responsible for intelligent behavior
      all derive from the inner workings of an individual agent. OBJECTIVES AND
      RESULTS: In this paper we argue that medical informatics commitment to the
      classical model of cognition conflates the processing performed by the minds of
      individual agents with the processing performed by the larger distributed
      activity systems within which individuals operate. We review trends in cognitive
      science that seek to close the gap between general-purpose models of cognition
      and applied considerations of real-world human performance. One outcome is the
      theory of distributed cognition, in which the unit of analysis for understanding
      performance is the activity system which comprises a group of human actors, their
      tools and environment, and is organized by a particular history of goal-directed
      action and interaction. CONCLUSION: We describe and argue for the relevance of
      distributed cognition to medical informatics, both for the study of human
      performance in healthcare and for the design of technologies meant to enhance
      this performance.

PMID- 17556015
TI  - Correlates of acute pain in herpes zoster.

PMID- 17556016
TI  - Hyperglycemia down-regulates apolipoprotein M expression in vivo and in vitro.
AB  - Diabetes is associated with low concentrations of apoM in plasma. In db/db mice,
      ob/ob mice as well as in the alloxan-induced diabetic mouse, the low apoM levels
      are paralleled by decreased expression of the apoM gene. In the latter model,
      insulin substitution tended to reverse the low apoM expression. It is not known
      whether the impairment in apoM expression can be ascribed to hyperglycemia,
      insulin deficiency or insulin resistance. In the present study, we investigated
      apoM levels and expression in rats rendered hyperglycemic by short-term glucose
      infusion. As expected, serum insulin concentrations rose moderately during the
      infusions. Serum apoM concentrations and hepatic apoM mRNA levels were
      significantly reduced in the hyperglycemic rats, indicating that the low
      expression of apoM in these diabetic models can be ascribed to hyperglycemia
      rather than to insulin deficiency or insulin resistance. However, in HepG2 cells
      both glucose and insulin markedly inhibited apoM expression these effects were
      additive. Thus, the possible effects of insulin in vivo seem to be mediated
      indirectly.

PMID- 17556017
TI  - Scavenger receptor class B, type I (SR-BI) homo-dimerizes via its C-terminal
      region: fluorescence resonance energy transfer analysis.
AB  - Expression of the scavenger receptor class B, type I (SR-BI) receptor facilitates
      high density lipoprotein cholesterol transport and correlates with protection
      against atherosclerosis. Studies have shown that SR-BI self-associates, but many
      of the techniques used to characterize SR-BI homo-oligomerization were wrought
      with the prospect of producing artifacts. Therefore, we employed fluorescence
      resonance energy transfer (FRET) to visualize SR-BI homo-oligomerization with the
      benefit of gaining information about its quaternary structure in the absence of
      typical membrane receptor artifacts. To this end, SR-BI was tagged at the N- or C
      termini with either cyan (CFP) or yellow (YFP) fluorescent protein. To test
      whether SR-BI subunits oligomerize through N-N, N-C or C-C terminal interactions,
      we co-expressed the appropriate SR-BI fusion protein combinations in COS-7 cells
      and measured live-cell FRET following acceptor photobleaching. We did not observe
      FRET with co-transfection of SR-BI with CFP and YFP at the N-termini nor at the N
      and C-termini, suggesting that the N-termini are not proximal to each other or
      to the C-termini. However, FRET was observed with co-transfection of SR-BI with
      CFP and YFP at the C-termini, suggesting that the C-terminal ends are within 10
      nm of each other, consistent with SR-BI dimerization via its C-terminal region.

PMID- 17556019
TI  - What's new in the Aire?
AB  - Unraveling the mechanisms underlying autoimmune disease remains a difficult
      challenge. Recent lessons learned from the study of AIRE (autoimmune regulator),
      the gene responsible for the rare monogenic human syndrome APS-1, highlight the
      power of genetics to reveal disease pathogenesis. With the discovery of AIRE,
      central tolerance has re-emerged as a crucial check against autoimmunity. Aire
      mediated regulation of diverse self-antigens in the thymus serves as a paradigm
      for the importance of promiscuous gene expression in the prevention of autoimmune
      disease. Recent characterization of Aire-targeted antigens continues to bear this
      out. Here, we review the current progress surrounding the role of Aire in central
      tolerance from a molecular, genetic and developmental basis.

PMID- 17556020
TI  - Evaluation of four rapid methods for hemoglobin screening of whole blood donors
      in mobile collection settings.
AB  - INTRODUCTION: Predonation hemoglobin measurement is a problematic requirement in
      mobile donation settings, where accurate determination of venous hemoglobin by
      hematology analyzers is not available. OBJECTIVE: We have evaluated hemoglobin
      screening in prospective donors by the semiquantitative copper sulphate test and
      by capillary blood samples analyzed by three portable photometers, HemoCue, STAT
      Site MHgb, and the CompoLab HB system. METHODS: Capillary blood samples were
      obtained from 380 donors and tested by the copper sulphate test and by at least
      one of the named portable photometers. Predonation venous hemoglobin was also
      determined in all donors using a Coulter Max-M analyzer. RESULTS: The three
      photometers provided acceptable reproducibility (CV below 5%), and displayed a
      significant correlation between the capillary blood samples and the venous
      hemoglobin (R2 0.5-0.8). HemoCue showed the best agreement with venous hemoglobin
      determination, followed by STAT-Site MHgb, and the CompoLab HB system. The copper
      sulphate test provided the highest rate of donors acceptance (83%) despite
      unacceptable hemoglobin levels, and the lowest rate for donor deferral (1%)
      despite acceptable hemoglobin levels. The percentage of donors correctly
      categorized for blood donation by the portable hemoglobinometers was 85%, 82%,
      and 76% for CompoLab HB system, HemoCue and STAT-Site, respectively. CONCLUSION:
      Our data suggest that hemoglobin determination remains a conflictive issue in
      donor selection in the mobile setting. Without appropriate performance control,
      capillary hemoglobin screening by either the copper sulphate method or by the
      novel portable hemoglobinometers could be inaccurate, thus potentially affecting
      both donor safety and the blood supply.

PMID- 17556021
TI  - Selected papers from the 15th Congress of the Interdisciplinary European Society
      for Hemapheresis and Hemotherapy.

PMID- 17556022
TI  - Therapeutic apheresis: results from a single center in Turkey.
AB  - BACKGROUND: Therapeutic apheresis (TA) is carried out for a broad spectrum of
      diseases and syndromes. AIM: We retrospectively evaluated the results of
      therapeutic apheresis (TA) including plasma exchange, therapeutic
      plateletpheresis, and leukapheresis during 2000-2006. METHODS: A total of 195
      procedures were performed in 44 patients (25 male and 19 female, with a mean age
      of 52+/-15 years). These procedures consist of 165 plasma exchanges, 20
      therapeutic plateletpheresis, and 10 leukapheresis. The most common indications
      were hematological, neurological, and metabolic diseases. Eighty-three percent of
      plasma exchange, 100% of plateletpheresis and leukapheresis belonged to
      indication Category I or II, according to the guidelines of the American Society
      for Apheresis. RESULTS: While hemoglobin levels significantly increased (p<0.05),
      platelet counts decreased (p<0.005) after plasma exchange. Hematological
      parameters did not statistically change significantly with leukapheresis
      (p>0.05). Platelet counts significantly decreased with plateletpheresis
      (p<0.001). Total complications were detected in 21% of the procedures. Adverse
      events (AE) were seen in 17% of the procedures. None of the patients died (Grade
      IV) from any complication. AEs occurred in 14% (Grade-I), 1% (Grade-II), and 2%
      (Grade-III) of the procedures. The most common AEs were nausea/vomiting,
      hypotension, and abdominal pain. CONCLUSION: TA, an important procedure in
      Transfusion Medicine, is safely carried out in our center in several
      hematological, neurological, and metabolic diseases which are similar to previous
      reports.

PMID- 17556023
TI  - Natural anti-GBM antibodies from normal human sera recognize alpha3(IV)NC1
      restrictively and recognize the same epitopes as anti-GBM antibodies from
      patients with anti-GBM disease.
AB  - Anti-GBM disease is a rare autoimmune condition characterized by autoantibodies
      targeting the alpha3 chain non-collagen 1 domain of type IV collagen
      (alpha3(IV)NC1). Recently, we isolated IgG reacting with alpha3(IV)NC1 from
      normal healthy human sera. The current study examined the antigen and epitope
      specificity of these natural autoantibodies (NAA) using recombinant human alpha1,
      3, 5(IV)NC1 and three constructs expressing, previously defined epitope regions
      designated E(A), E(B) and S2, in the alpha1(IV)NC1 background. The NAA
      preparations reacted with recombinant human alpha3(IV)NC1 to the same extent as
      with purified bovine alpha(IV)NC1, but not with recombinant human alpha1 and
      alpha5(IV)NC1. NAA preparations recognized the three chimeric proteins (E(A),
      E(B) and S2) yielding similar absorbance values. We conclude that anti-GBM NAA
      recognize the same major epitopes as anti-GBM antibodies from patients with
      Goodpasture's disease.

PMID- 17556025
TI  - Shift of CMV-specific CD4+ T-cells to the highly differentiated CD45RO-CD27-
      phenotype parallels loss of proliferative capacity and precedes progression to
      HIV-related CMV end-organ disease.
AB  - To identify factors related to progression to CMV end-organ disease, cytokine
      production, proliferative capacity and phenotype of CMV-specific CD4(+) T-cells
      were analysed longitudinally. Numbers of IFNgamma(+)CD4(+) and IFNgamma(+)IL
      2(+)CD4(+) T-cells tended to decrease in individuals progressing to AIDS with CMV
      end-organ disease (AIDS-CMV), whereas they remained detectable in long-term
      asymptomatics (LTAs) and progressors to AIDS with opportunistic infections (AIDS
      OI). In parallel, CMV-specific proliferative capacity was lost in AIDS-CMV.
      Initially, the majority of the CMV-specific IFNgamma(+)CD4(+) T-cells were of the
      CD45RO(+)CD27(-) subset, but during progression to AIDS-CMV a shift in phenotype
      to the CD45RO(-)CD27(-) subset was observed. Our data indicate that a decrease in
      CMV-specific cytokine production and proliferative capacity precedes progression
      to AIDS-CMV. Accumulation of CD4(+) T-cells with a CD45RO(-)CD27(-) phenotype
      suggests that persistent antigen exposure drives differentiation of CMV-specific
      CD4(+) T-cells towards a poorly proliferating, and highly differentiated
      "effector" subset, which eventually fails to produce IFNgamma in patients
      developing AIDS-CMV.

PMID- 17556024
TI  - High serum levels of BAFF, APRIL, and TACI in common variable immunodeficiency.
AB  - Common variable immunodeficiency (CVID) is characterized by low levels of immune
      globulins and lack of antibody. Mutations in transmembrane activator and calcium
      modulating cyclophilin ligand (TACI), are found in 8-10%, associated with
      autoimmunity and splenomegaly. Some patients with mutations had increased serum
      levels of TACI. Because of this, and the prevalence of autoimmunity,
      splenomegaly, and lymphadenopathy, we quantitated levels of TACI ligands, a
      proliferation inducing ligand (APRIL) and B cell activating factor (BAFF) and
      TACI in serum of 77 patients. CVID subjects had markedly increased serum levels
      of BAFF (p<0.0001), APRIL (p<0.0001), and TACI (p=0.001) but there was no
      relationship between levels and autoimmunity, lymphadenopathy, splenomegaly, B
      cell numbers, or mutations in TACI. Peripheral blood mononuclear cells of CVID
      subjects had increased levels of BAFF mRNA. We conclude that increased
      constitutive production and/or underlying immuno-regulatory or inflammatory
      conditions lead to enhanced release of ligands; however, the biological result
      remains unclear.

PMID- 17556026
TI  - The neurobiology of attention-deficit/hyperactivity disorder.

PMID- 17556027
TI  - Gastrointestinal safety of cyclooxygenase-2 inhibitors: a Cochrane Collaboration
      systematic review.
AB  - BACKGROUND & AIMS: Nonselective non-steroidal anti-inflammatory drugs (NSAIDs)
      and cyclooxygenase-2 inhibitors (COX-2s) are used to treat a variety of arthritic
      and inflammatory conditions. The aim of this study was to assess the upper
      gastrointestinal (GI) harms of the long-term use of COX-2s, compared with
      nonselective NSAIDs and placebo, in arthritis sufferers. METHODS: A systematic
      review of randomized controlled trials (RCTs) was conducted. Searches were
      conducted in (1) Cochrane Central Register of Controlled Trials (CENTRAL), (2)
      the Cochrane Collaboration Library (2005), (3) MEDLINE (to December 2006), and
      (4) Excerpta Medica Database (EMBASE) (to June 2005). Reference lists from trials
      and abstracts of conference proceedings were searched by hand, and experts were
      contacted to identify further relevant trials. RCTs of celecoxib, rofecoxib,
      etoricoxib, valdecoxib, and lumiracoxib were included if they reported on
      endoscopic ulcers, clinically important ulcer complications, or adverse
      gastrointestinal (GI) symptoms with the use of these COX-2s, compared with
      placebo or with nonselective NSAIDs. Study selection and data extraction were
      performed in duplicate by independent reviewers. Data were analyzed by using
      Review Manager 4.2 in accordance with accepted meta-analysis techniques. RESULTS:
      Compared with nonselective NSAIDs, COX-2s produced significantly fewer
      gastroduodenal ulcers (relative risk, 0.26; 95% confidence interval, 0.23-0.30)
      and clinically important ulcer complications (relative risk, 0.39; 95% confidence
      interval, 0.31-0.50), as well as fewer treatment withdrawals caused by GI
      symptoms. The co-administration of acetylsalicylic acid appears to reduce the GI
      safety of COX-2s in subgroup analyses. CONCLUSIONS: COX-2s appear to offer
      greater upper GI safety and are better tolerated than nonselective NSAIDs. The co
      administration of acetylsalicylic acid might reduce the safety advantage of COX
      2s over that of nonselective NSAIDs.

PMID- 17556028
TI  - Multidetector row CT of small bowel tumours.
AB  - Computed tomography is being increasingly used for the evaluation of patients
      with vague abdominal symptoms, and may provide the initial opportunity to detect
      and characterize tumours of the small bowel. The recognition of imaging features
      on CT allows distinction to be made between benign and malignant neoplasms.
      Multidetector row CT (MDCT) provides high-resolution imaging and helps in precise
      localization and characterization of lesions. This article illustrates the
      imaging appearances of small bowel tumours on MDCT and demonstrates the
      usefulness of multiplanar reformatting (MPR) in the diagnosis and categorization
      of these tumours.

PMID- 17556029
TI  - Imaging manifestations of neck masses in the immunocompromised host.
AB  - Human immunodeficiency virus (HIV) infection, haematological malignancy, and
      immunosuppression for transplantation and autoimmune disorders have led to a
      large increase in immunocompromised patients. Neck masses are relatively common
      in this patient group and include both opportunistic and severe manifestations of
      common infections, benign hyperplasia, and primary or secondary malignancies.
      Although biopsy may be necessary for definitive diagnosis, features on cross
      sectional imaging may suggest a specific diagnosis or limit the differential
      diagnosis and facilitate optimal patient management. This article will review
      critical aspects of neck anatomy, illustrate the spectrum of imaging features,
      and discuss the interpretative pearls and pitfalls when evaluating neck masses in
      immunocompromised patients.

PMID- 17556030
TI  - Imaging of pericardial diseases.
AB  - Traditionally echocardiography has been the method of choice for the evaluation
      of pericardial and cardiac lesions. However, computed tomography (CT) and
      magnetic resonance imaging (MRI) provide a large field of view and excellent
      images of anatomy not available with echocardiography. In addition, CT and MRI
      demonstrate high soft-tissue contrast as well as the exact localization of a
      lesion. Currently, CT and MRI are the preferred techniques for the recognition
      and characterization of pericardial disorders. In this review, the characteristic
      imaging appearances of a variety of pericardial diseases are discussed.

PMID- 17556031
TI  - Multi-detector row CT coronary angiography in patients with cardiomyopathy --
      initial single-centre experience.
AB  - AIMS: To evaluate the diagnostic accuracy of computed tomography (CT) in
      assessing haemodynamically significant coronary artery stenoses in patients with
      cardiomyopathy (CM). SUBJECTS AND METHODS: Eighteen patients with CM were
      approached to undergo CT coronary angiography to evaluate the use of this
      technique for investigating the presence of significant coronary artery disease
      (CAD), and also to compare the findings with catheter angiography. RESULTS: On a
      segment-by-segment analysis the sensitivity, specificity, positive and negative
      predictive values in the CM group were 66.7, 96.5, 40 and 98.8%, respectively,
      with 100% accuracy in "whole-patient terms". CONCLUSION: Non-invasive, 16
      detector row CT coronary angiography in patients with presumed CM would seem to
      be a useful clinical tool for the exclusion of significant coronary artery
      disease. However, the presence of suboptimal contrast opacification in this
      patient group means that the implication of these results must be interpreted
      with caution.

PMID- 17556032
TI  - Analysis of the factors associated with radiofrequency ablation-induced
      pneumothorax.
AB  - AIM: To define the characteristics most likely to result in radiofrequency
      ablation (RFA)-induced pneumothorax. METHODS AND MATERIALS: CT-guided RFA was
      performed in 79 tumours in 55 lungs in 37 patients, 16 were women, mean age 62
      years (range 34-83). Three had primary lung cancer, 34 had metastases. The
      number, size, and location of tumours, electrode type, treatment parameters,
      length of electrode trajectory through aerated lung, background emphysema, prior
      interventions, and use of positive-pressure ventilation were analysed. The size,
      timing of any pneumothoraces, and intervention were recorded. RESULTS:
      Pneumothorax occurred in 21 of the 25 lungs treated (38%), 18 immediate and three
      delayed. Seventeen of the 21 (81%) occupied less than 30% of the hemithorax,
      whereas in four cases >31% was involved. Eight of the 55 (15%) pneumothoraces
      required aspiration. The length of the electrode trajectory through aerated lung
      in those who developed a pneumothorax was 5.4+/-4.7cm versus 1.9+/-2.7 in those
      who did not (p=0.001). The mean number of tumours ablated was higher in the
      pneumothorax group, 1.7+/-1 versus 1.3+/-0.6 (p=0.03), as was the number of
      electrode positions, 6+/-3.9 versus 3.6+/-2.2 (p=0.01). On multivariate analysis
      only the needle trajectory through aerated lung was significant (p=0.04).
      CONCLUSIONS: The number of tumours, electrode positions, and the anticipated
      electrode trajectory through aerated lung impacts on the likelihood of a
      pneumothorax. These considerations should be factored into patient selection, the
      choice of approach, and trajectory used in RFA.

PMID- 17556033
TI  - CT colonography versus colonoscopy in the follow-up of patients after
      diverticulitis - a prospective, comparative study.
AB  - AIM: To assess whether computed tomography colonography (CTC) is a viable
      alternative to colonoscopy or double contrast barium enema in the follow-up of
      patients after diverticulitis. MATERIAL AND METHODS: Fifty patients underwent CTC
      followed immediately by colonoscopy. Results were blinded to the examiners.
      Findings of diverticular disease and patient acceptance were evaluated. RESULTS:
      Bowel preparation and distension were good in the majority of CTC and colonoscopy
      examinations. Diverticular disease was found in 96% of patients at CTC and in 90%
      at colonoscopy. The rate of agreement between CTC and colonoscopy for
      diverticular findings in the sigmoid colon was good (kappa=0.64). No
      complications were seen. Patients found colonoscopy more uncomfortable (p<0.03),
      more painful (p<0.001), and more difficult (p<0.01) than CTC. Of the patients
      favouring one examination, 74% preferred CTC. CONCLUSION: CTC appears to have a
      better diagnostic potential for imaging of diverticular disease-specific
      findings, when compared with colonoscopy. Also, CTC was less uncomfortable and
      was preferred by a majority of patients. CTC seems to be a reasonable alternative
      in follow-up of patients with symptomatic diverticular disease.

PMID- 17556034
TI  - Virtual colonoscopy training and accreditation: a national survey of radiologist
      experience and attitudes in the UK.
AB  - AIM: Expert consensus recommends directed training and possibly in the future,
      formal accreditation before independent virtual colonoscopy (VC) reporting. We
      surveyed radiologists' experience of VC training, compared with barium enema, and
      assessed attitudes towards accreditation. MATERIALS AND METHODS: A questionnaire
      was sent to 78 consultant radiologists from 72 centres (65 National Health
      Service hospitals; seven independent primary screening centres) offering a VC
      service. RESULTS: Fifty-four (69%) eligible radiologists responded. They had
      interpreted 18,152 examinations (range 3-1500) in total versus 232,350 (13 times
      more) barium enemas. Twenty-two (41%) deemed their VC training as inadequate
      [including five (45%) of screening centre radiologists], and only 14 (26%) had
      attended a training workshop due to lack of availability (54%) or financial/study
      leave constraints (24%). Eleven (20%) radiologists routinely double-reported VC
      examinations versus 37 (69%) barium enemas, yet 21 (39%) considered requirements
      for VC training were greater than barium enema. Thirty-eight (70%) favoured
      accreditation beyond internal audit for VC versus 15(28%) for barium enema. Of
      these 38, seven (18%) favoured "one-off," and 18 (47%) periodic testing, with 16
      (42%) favouring external audit alone or in combination with testing. Overall, 42
      (78%) considered specific accreditation for reporting screening examinations
      appropriate and 45 (83%) respondents preferred a national radiological
      organization to regulate such a scheme. CONCLUSION: There is wide variability in
      reporting experience and recommendations for VC training have not been widely
      adopted, in part due to limited access to dedicated workshops. UK radiologists
      are generally in favour of VC accreditation, governed by a national radiology
      organization.

PMID- 17556035
TI  - CT enteroclysis in the diagnosis of obscure gastrointestinal bleeding: initial
      results.
AB  - AIM: To evaluate the usefulness of computed tomography (CT) enteroclysis in
      patients with obscure gastrointestinal (GI) bleeding. MATERIALS AND METHODS: In a
      prospective study, CT enteroclysis was performed in 21 patients (median age 50
      years; range 13-71 years) with obscure GI bleeding in which the source of the
      bleeding could not be detected despite the patient having undergone both upper GI
      endoscopic and colonoscopic examinations. The entire abdomen and pelvis was
      examined in the arterial and venous phases using multisection CT after distending
      the small intestine with 2l of 0.5% methylcellulose as a neutral enteral contrast
      medium and the administration of 150ml intravenous contrast medium. RESULTS:
      Adequate distension of the small intestine was achieved in 20 of the 21 (95.2%)
      patients. Potential causes of GI bleeding were identified in 10 of the 21 (47.6%)
      patients using CT enteroclysis. The cause of the bleeding could be detected nine
      of 14 (64.3%) patients with overt, obscure GI bleeding. However, for patients
      with occult, obscure GI bleeding, the cause of the bleeding was identified in
      only one of the seven (14.3%) patients. The lesions identified by CT enteroclysis
      included small bowel tumours (n=2), small bowel intussusceptions (n=2),
      intestinal tuberculosis (n=2), and vascular lesions (n=3). All vascular lesions
      were seen equally well in both the arterial and venous phases. CONCLUSIONS: The
      success rate in detection of the cause of bleeding using CT enteroclysis was
      47.6% in patients with obscure GI bleeding. The diagnostic yield was higher in
      patients with overt, obscure GI bleeding than in those with occult obscure GI
      bleeding.

PMID- 17556036
TI  - Application of percutaneous ultrasound-guided treatment for ultrasonically
      invisible hypervascular hepatocellular carcinoma using microbubble contrast
      agent.
AB  - AIM: To evaluate the efficacy of contrast-enhanced ultrasound for the
      localization of ultrasonically invisible hypervascular lesions in the liver to
      facilitate percutaneous ultrasound-guided treatment. MATERIALS AND METHODS: Forty
      patients with 47 ultrasonically invisible hypervascular lesions (5-20mm)
      diagnosed on contrast-enhanced computed tomography were enrolled in the
      retrospective study. Contrast-enhanced ultrasound (CEUS) with Levovist was
      performed to localize the lesions both in the early phase and liver-specific
      phase. Diagnosis of was confirmed by percutaneous needle biopsy where feasible,
      and on the basis of on treatment outcomes or changes in computed tomography
      findings in those not amenable to biopsy. RESULTS: Thirty-two lesions were
      diagnosed as hepatocellular carcinoma (HCC). Contrast-enhanced ultrasound
      localized hepatocellular carcinoma in 24/32 (75%) lesions, the mean diameter
      (15.1+/-4.9mm), as measured using computed tomography, being significantly larger
      than that of the remaining eight lesions (10.5+/-2.1mm). Ultrasound-guided
      treatment was performed in 19 of the 24 lesions, and transarterial
      chemoembolization (TACE) was applied for the other five lesions because of
      difficult percutaneous access. Five of the eight non-visualised lesions were
      treated by transarterial chemoembolization, and the other three by surgical
      resection. The beneficial effect of CEUS was significantly greater when the
      reason for poor initial visualisation was the coarse liver architecture (17/17)
      than when it was due to adverse location (seven of 15, p<0.005). Fifteen of the
      CT-detected hypervascular lesions were considered to represent false positives
      for HCC, based on their behaviour during follow-up. CONCLUSION: Contrast-enhanced
      ultrasound with Levovist facilitates the application of percutaneous ultrasound
      guided treatment by improving localization of ultrasonically invisible
      hypervascular hepatocellular carcinomas in the liver.

PMID- 17556037
TI  - A prospective evaluation of CT features predictive of intra-abdominal
      hypertension and abdominal compartment syndrome in critically ill surgical
      patients.
AB  - AIM: The aim of this study was to validate the computed tomography (CT) features
      of intra-abdominal hypertension (IAH) by relating them to the clinical
      measurement of intra-abdominal pressure (IAP) in critically ill surgical
      patients. MATERIALS AND METHODS: The intra-vesical pressure was measured to
      reflect IAP in 24 critically ill patients. CT examinations obtained within 24h of
      IAP measurement were reviewed and scored independently by two consultant
      radiologists. Each CT examination was scored for the seven proposed features of
      IAH. Images obtained during the presence of IAH were compared with those obtained
      in the absence of IAH. RESULTS: Forty-eight abdominal CT examinations were
      evaluated, of which 18 (38%) were obtained in the presence of IAH, whereas eight
      (17%) were obtained in the presence of abdominal compartment syndrome (ACS). At
      CT, the round belly sign (RBS) and bowel wall thickening with enhancement (BWTE)
      were significantly more frequently detected during the presence of IAH than when
      the IAP was less than 12 mmHg (78 versus 20% of examinations, p<0.001 and 39
      versus 3% of examinations, p=0.003, respectively), but only BWTE was
      significantly associated with the presence of ACS (40 versus 11% of examinations,
      p=0.047). CONCLUSION: The presence of RBS and BWTE on CT images of critically ill
      surgical patients should alert clinicians to the possibility of presence of IAH
      and ACS, and prompt measurement of the IAP and consideration of suitable
      interventions.

PMID- 17556038
TI  - Ultrasound-guided percutaneous drainage of meniscal cysts: preliminary clinical
      experience.
AB  - AIM: To evaluate the efficacy of ultrasound-guided percutaneous drainage of
      symptomatic meniscal cysts. MATERIALS AND METHODS: Patients with lateral knee
      joint tenderness and swelling and confirmed meniscal cyst on magnetic resonance
      imaging (MRI) were consecutively enrolled for ultrasound-guided percutaneous cyst
      aspiration. Cysts were injected with local anaesthetic and steroid before
      completion of procedure. All 18 patients (all male, average age 33 years) were
      subsequently followed up (average time 10 months) and meniscal cyst symptoms
      assessed by questionnaire. Fischer's exact test used to analyse the data.
      RESULTS: In every case the procedure was well tolerated, and each patient
      indicated that they would be willing to have a repeat procedure in the future.
      Ten patients reported complete resolution of symptoms secondary to therapeutic
      cyst aspiration and had resumed participation in high-performance sport. Two
      patients reported a satisfactory sustained response, reporting only occasional
      "twinges of pain". In the remaining six patients, symptoms returned after an
      initial pain-free period. The pain-free period ranged from 1-8 weeks. In this
      study, patient outcome did not significantly correlate with any meniscal cyst
      characteristic. CONCLUSION: Ultrasound-guided percutaneous aspiration of meniscal
      cysts is a well-tolerated, simple, and safe procedure. In this small patient
      series, it was associated with positive early results with favourable outcomes in
      the mid to long-term. It should be considered in patients unsuitable for surgical
      debridement or as an interim therapy if surgery is delayed or postponed.

PMID- 17556039
TI  - Analysis of five cases of splanchnic artery aneurysm associated with coeliac
      artery stenosis due to compression by the median arcuate ligament.
AB  - AIM: To elucidate the mechanism of occurrence of splanchnic artery aneurysm
      associated with coeliac artery stenosis due to compression by the median arcuate
      ligament, and also to discuss the management for this relatively rare condition.
      MATERIALS AND METHODS: Five consecutive cases of splanchnic artery aneurysm
      associated with coeliac axis stenosis due to compression by the median arcuate
      ligament, including four cases of pancreaticoduodenal artery aneurysm and one
      case of epiploic artery aneurysm, were investigated. These cases were collected
      over a 5-year period in our local and affiliated hospitals. Among these five
      cases, three were discovered because of rupture of the aneurysm, and two were
      found incidentally in annual medical check-ups. RESULTS: In all cases,
      conspicuously developed collateral arteries, which were of the dilated
      pancreaticoduodenal arcade and its branches, were conspicuously found on digital
      subtraction angiography of the superior mesenteric artery. The findings suggested
      that haemodynamic changes in the splanchnic arterial networks (an increase in
      blood flow mainly through the pancreaticoduodenal arcade), were the possible
      cause of the corresponding aneurysms. CONCLUSION: Compression by the median
      arcuate ligament might be a frequent cause of splanchnic aneurysm, which, on
      rupture of the aneurysm, could be life-threatening.

PMID- 17556040
TI  - How clean is your probe? Microbiological assessment of ultrasound transducers in
      routine clinical use, and cost-effective ways to reduce contamination.

PMID- 17556041
TI  - A new CT artefact - the bubble curve sign.

PMID- 17556042
TI  - Blood-stained, acute subdural hygroma mimicking a subacute subdural haematoma in
      non-accidental head injury.

PMID- 17556043
TI  - Multicentric hyaline-vascular Castleman's disease.

PMID- 17556044
TI  - Re: computed tomographic colonography (CTC) performance: one-year follow-up.

PMID- 17556047
TI  - Autonomic nervous system activity in premature and full-term infants from
      theoretical term to 7 years.
AB  - The premature population reaching theoretical term suffers from a major deficit
      in autonomic nervous system (ANS) activity, as can be seen from heart rate
      variability indices. Whether this autonomic function recovers in the long term is
      not yet established. Thus, we analyzed and compared ANS activity indices, at
      birth or at the time of the theoretical term, and at ages 2-3 and 6-7 years, in
      two populations: a group of 30 premature children and a reference group of 14
      full-term age-matched newborns. Using Fourier Transform analysis, we studied 24-h
      ECG Holter recordings to establish heart rate variability indices: Ptot, VLF, LF,
      HF, ratio LF/HF, LFnu, HFnu. In the neonatal period, sympathetic and even more
      markedly, parasympathetic activities were very low in prematures compared to the
      reference full-term group. At ages 2-3 and 6-7 years, prematures had recovered
      and had similar ANS activity as the full-term group. These data suggest a fast
      ANS maturation in prematures during the two first years of life, with a higher
      speed of recovery for the parasympathetic arm. Furthermore, compared evolution
      shows a faster ANS maturation in premature. Potential mechanisms are discussed.

PMID- 17556048
TI  - The Bre5/Ubp3 ubiquitin protease complex from budding yeast contributes to the
      cellular response to DNA damage.
AB  - The ubiquitination status of proteins can control numerous aspects of protein
      function through targeted destruction or by altering protein-protein
      interactions, subcellular localization, or enzymatic activity. In addition to
      enzymes that mediate the conjugation of ubiquitin moieties to target proteins,
      there are enzymes that catalyze the removal of ubiquitin, termed ubiquitin
      proteases. One such ubiquitin protease, Ubp3, exists in a complex with a partner
      protein: Bre5. This complex has been implicated in a variety of cellular
      activities, and was recently identified in large-scale screens for genetic
      interactions with known components of the DNA damage response pathway. We found
      that this complex plays a role in the cellular response to the DNA damaging agent
      phleomycin and strains lacking the complex have a defect in non-homologous end
      joining. Although this complex is also important for telomeric silencing,
      maintenance of the cell wall, and global transcriptional regulation, we present
      evidence suggesting that the role of this complex in DNA damage responses is
      distinct from these other roles. First, we found that Ubp3/Bre5 functions
      antagonistically with Bul1 in DNA damage responses, but not in its other cellular
      functions. Additionally, we have generated mutants of Bre5 that are specifically
      defective in DNA damage responses.

PMID- 17556049
TI  - Human NEIL1 localizes with the centrosomes and condensed chromosomes during
      mitosis.
AB  - The DNA glycosylase hNEIL1 initiates base excision repair (BER) of a number of
      oxidized purines and pyrimidines in cellular DNA and is one of three mammalian
      orthologs of the Escherichia coli Nei/Fpg enzymes. Human NEIL1 has been purified
      and extensively characterized biochemically, however, not much is known about its
      intracellular distribution. In the present work, we have studied the cellular
      localization of hNEIL1 using both antibodies raised against the full-length
      recombinant protein and a stable HeLa cell line expressing hNEIL1 fused N
      terminal to EGFP. The results presented reveal an intricate mitotic distribution
      of hNEIL1. Centrosomal localization of hNEIL1 was observed when mitotic HeLa
      cells were immunostained with hNEIL1 antibodies. This localization was confirmed
      when Western blots of isolated centrosomes from stably expressing hNEIL1-EGFP
      HeLa cells were probed with GFP or hNEIL1 antibodies, even though a fluorescent
      signal could not be detected in the centrosomes of these cells. Human NEIL1 was
      also shown to be associated with mitotic condensed chromosomes. Notably, the
      interaction of hNEIL1 with condensed chromatin was disrupted when cells were
      fixed with chemical fixatives that are regularly used in immunodetection
      techniques.

PMID- 17556050
TI  - Application of a metabolomic method combining one-dimensional and two-dimensional
      gas chromatography-time-of-flight/mass spectrometry to metabolic phenotyping of
      natural variants in rice.
AB  - We have developed a comprehensive method combining analytical techniques of one
      dimensional (1D) and two-dimensional (GC x GC) gas chromatography-time-of-flight
      (TOF)-mass spectrometry. This method was applied to the metabolic phenotyping of
      natural variants in rice for the 68 world rice core collection (WRC) and two
      other varieties. Ten metabolites were selected as metabolite representatives, and
      the selected ion current of each metabolite peak obtained from both techniques
      were statistically compared. Our method of combining 1D- and GC x GC-TOF/MS is
      useful for the metabolic phenotyping of natural variants in rice for further
      studies in breeding programs.

PMID- 17556051
TI  - Two distinct sites of interaction form the calponin: gelsolin complex and two
      calcium switches control its activity.
AB  - Gelsolin and calponin are well characterized actin-binding proteins that form a
      tight gelsolin:calponin complex (GCC). We show here that the GCC is formed
      through two distinct interfaces. One of these is formed between 144-182 of
      calponin and 25-150 of gelsolin (G1). The second is a calcium-sensitive site
      centred on calponin's CH domain, and the C-terminal half of gelsolin (G4-6). The
      behaviour of this second interface is dependent on the presence of calcium and so
      it is possible that potential GCC-binding partners may be selected by calcium
      availability. Actin is one such GCC-binding partner and we show that a larger
      complex is formed with monomeric actin in calcium. The stoichiometry of this
      complex is determined to be 1 gelsolin/1 calponin/2 G-actins (GCA(2)). Both actin
      monomers bind the GCC through gelsolin. Both calponin and gelsolin are reported
      to play signaling roles in addition to their better-characterized actin-binding
      properties and it is possible that the GCC regulates both of these functions.

PMID- 17556052
TI  - Analysis of peroxiredoxin decreasing oxidative stress in hypertensive aortic
      smooth muscle.
AB  - To determine the role of peroxiredoxin (Prx) in response to oxidative stress and
      during hypertension in the vasculature, we identified Prx proteins and analyzed
      their antioxidant effects. Rat aortic smooth muscle contains all six Prxs (I-VI).
      Prx I, II, and VI shifted to its acidic site on two-dimensional polyacrylamide
      gel electrophoresis after exposure to H(2)O(2). The total expression of Prx I and
      VI was increased in response to H(2)O(2). The expression of Prx I, but not that
      of Prx II and VI, increases and the acidic form of Prx I and the sulfonic acid
      form of Prx (SO(3)H-Prx) are more strongly expressed in the aortic smooth muscle
      of hypertensive rats than in that of normotensive control rats. Prxs were also
      found in the mesenteric artery, heart, and kidney. The expression levels of Prx I
      and VI were increased in mesenteric artery, but not heart and kidney, from
      hypertensive rats compared with that from normotensive rats. These results
      suggest that Prxs play a crucial role against oxidative stress in vascular smooth
      muscles during hypertension.

PMID- 17556053
TI  - Stability of highly purified human paraoxonase (PON1): association with human
      phosphate binding protein (HPBP) is essential for preserving its active
      conformation(s).
AB  - The biological role of human paraoxonase (PON1) remains unclear, whilst there is
      a consensus that the enzyme has a protective influence. A toxicological role,
      protecting from environmental poisoning by organophosphate derivatives drove
      earlier works, and more recently, clinical interest has focused on a protective
      role in vascular disease. PON1 resides essentially on HDL particles, a complex
      and dynamic molecular environment. Our recent discovery of the human phosphate
      binding protein (HPBP), displaying a firm propensity to associate with PON1, has
      steered new directions for characterizing PON1 functional state. Here, we report
      investigations on the effect of HPBP on oligomerization, storage and thermal
      stability of PON1. We found that purified PON1 is as a mixture of at least two
      states, and that the absence of HPBP favors homo-oligomerization of PON1 into
      state(s) of higher molecular size. We showed that HPBP allows stabilizing active
      conformation(s) of PON1 disencumbered of its natural environment. We also showed
      that PON1 exhibits intrinsically a remarkable thermal stability, and that the
      association of HPBP strongly contributes to slow the denaturation rate. A hybrid
      recombinant PON1 was shown more thermostable than the human enzyme, and its
      stability was unaffected by the presence of HPBP. Altogether, the results
      strongly encourage further study of the human enzyme.

PMID- 17556054
TI  - A cautionary note for the use of the McGhan 133LV Biodimensional Breast Tissue
      Expander.

PMID- 17556055
TI  - Coexisting harlequin and Horner syndromes after paediatric neck dissection: a
      case report and a review of the literature.
AB  - Harlequin syndrome, the presentation of hemifacial flushing and sweating, is a
      well recognized, though rarely reported, phenomenon associated with cervical
      sympathetic trauma. It is thought to result from disruption to sudomotor and
      vasomotor neurons present in the cervical sympathetic chain. The more common
      Horner's syndrome classically comprises the triad of unilateral miosis, ptosis
      and ipsilateral facial anhydrosis, and may also present as a sequela of cervical
      sympathetic denervation. We report a 26-month-old child with concomitant Horner's
      and harlequin syndromes, following neck dissection to address a large cervical
      lymphatic malformation. To our knowledge this is the first reported case of both
      syndromes resulting from surgery, and illustrates the particular challenge of
      lymphatic malformations in neck surgery due to their non-adherence to anatomical
      planes.

PMID- 17556057
TI  - Use of videography in the diagnosis of exercise-induced vocal cord dysfunction: a
      case report with video clips.

PMID- 17556058
TI  - Integrin beta 3 genotype influences asthma and allergy phenotypes in the first 6
      years of life.
AB  - BACKGROUND: The integrin beta3 gene (ITGB3) encodes a subunit of the platelet and
      monocyte-specific fibrinogen receptor and the widely expressed vitronectin
      receptor, which have diverse roles in cell migration, adhesion, and signaling.
      Previous work from our laboratory reported associations between single nucleotide
      polymorphisms (SNPs) in ITGB3 and asthma and allergic sensitization in 4
      populations. OBJECTIVE: To examine whether SNPs in ITGB3 are associated with the
      development of asthma and allergic phenotypes in early life. METHODS: We typed 13
      SNPs in 206 children participating in a birth cohort study and tested for
      associations with asthma and allergy phenotypes in the first 6 years of life.
      RESULTS: Our study revealed significant associations between SNPs in ITGB3 and
      asthma, wheezing, and IgE levels, suggesting an early role for this gene in the
      development of asthma and allergy. In particular, SNPs at the 3' end of the gene
      were significantly associated with IgE levels beginning at 1 year of age, whereas
      a SNP in intron 1 showed significant interaction effects with viral respiratory
      illness in infancy on asthma susceptibility. CONCLUSION: Our results suggest that
      genetic variation in ITGB3 contributes to asthma susceptibility and allergic
      sensitization, and that the effects of this gene begin early in life. Similar to
      our earlier study, different SNPs in the gene are associated with asthma and IgE.
      CLINICAL IMPLICATIONS: ITGB3 may play an important role in the development of
      asthma and allergy and may represent a potential therapeutic target for the
      treatment of these disorders.

PMID- 17556059
TI  - Coming back to a missing immune deviation as the main explanatory mechanism for
      the hygiene hypothesis.

PMID- 17556060
TI  - Relevance of H1-receptor occupancy to H1-antihistamine dosing in children.

PMID- 17556061
TI  - Identification of 2 new sesame seed allergens: Ses i 6 and Ses i 7.

PMID- 17556063
TI  - Commentary on ISCN 2005.

PMID- 17556064
TI  - XRCC1 codon 399 and ERCC2 codon 751 polymorphism, smoking, and drinking and risk
      of esophageal squamous cell carcinoma in a North Indian population.
AB  - XRCC1 (X-ray cross-complementing group 1) codon 399 and ERCC2 (excision repair
      cross-complementing group 2) codon 751 polymorphisms were studied in esophageal
      squamous cell carcinoma (ESQCC) in a North Indian population. Peripheral blood
      samples of 120 cases and 160 age-and-gender matching controls were collected from
      North India and the two polymorphisms were studied by means of polymerase chain
      reaction-restriction fragment length polymorphism techniques. The data were
      analyzed with a logistic regression model. The XRCC1 codon 399 Gln/Gln genotype
      was significantly associated with reduced risk of ESQCC (OR = 0.31, 95% CI = 0.12
      0.78, P = 0.01). In smokers, the XRCC1 Arg/Gln genotype was marginally and
      statistically nonsignificantly (OR = 1.5) associated with increased risk of this
      cancer. In drinkers, the XRCC1 Gln/Gln genotype was significantly protective (OR
      = 0.06, 95% CI = 0.007-0.605, P = 0.03), whereas ERCC2 (Lys/Gln-Gln/Gln) was
      marginally associated with increased risk (OR = 2.1, 95% CI = 0.46-9.44). Upon
      analysis of gene-gene interaction, a relationship was observed, although
      statistically nonsignificant, between combined genotypes of XRCC1 (Arg/Gln
      Gln/Gln)-ERCC2 Gln/Gln (OR = 0.33, 95% CI = 0.09-1.16) and XRCC1 (Gln/Gln)-ERCC2
      (Lys/Gln) (OR = 0.36, 95% CI = 0.11-1.17) and reduced risk of ESQCC in the North
      Indian population. These observations suggest that the Gln/Gln genotype of XRCC1
      might play an important role in DNA repair in ESQCC.

PMID- 17556065
TI  - Application of growth factor stimulants improves cytogenetic analysis of chronic
      myeloproliferative disorder patients without alteration to cell lineage or
      clonality.
AB  - Conventional cytogenetic methods rely on culturing bone marrow aspirates to
      obtain suitable and sufficient mitotic figures for G-banded analysis. Samples
      from patients with chronic myeloproliferative disorders (CMPD) often have
      increased failure rates due to reduced growth and poor morphology, all of which
      hamper the conventional karyotyping investigation. The application of growth
      factor (GF) stimulants to bone marrow aspirates has been shown to yield
      significant increases in both the quality and quantity of bone marrow metaphases
      obtained in 53 CPMD patient samples. All cultures were stimulated using the
      conditioned supernatant from the human bladder carcinoma cell line 5637, which
      contains IL-3, IL-6, and G-CSF. Results were assessed qualitatively on G-banded
      preparations and quantitatively by mitotic index (MI = % dividing cells). To
      assess whether the application of GF stimulants leads to clonal selection,
      culture samples from 15 patients were analyzed by fluorescence in situ
      hybridization, which supported the theory that clonal selection remains unaltered
      in GF-stimulated cultures. In addition to this immunophenotyping of cells, we
      demonstrated the lineage of cells propagated under these conditions. Cell markers
      were chosen to characterize B-lymphoid, T-lymphoid, myeloid, and primitive cell
      types. Results indicated that T cells were maintained in culture and B-lymphoid
      markers remained negative. In the myeloid subset, there was an overall reduction
      in the pan-myeloid markers. We believe this represents the loss of terminally
      differentiated cells (e.g., neutrophils) in culture. Overall, the study clearly
      demonstrates that the application of GF stimulants does not alter clonality or
      cell lineage propagated in these samples and is therefore suitable for
      application in diagnostic cytogenetic laboratories.

PMID- 17556066
TI  - Down-regulation of the progesterone receptor by the methylation of progesterone
      receptor gene in endometrial cancer cells.
AB  - Progesterone plays an important role in the regulation of normal endometrium
      function by binding to progesterone receptor (PR). In endometrial cancer,
      however, PR is always down-regulated. Previous reports showed that methylation in
      the promoter region of the PR gene may be responsible for PRB isoform repression.
      However, the CpG islands in the exon region of the PR gene are much richer and
      longer than in the promoter region. We hypothesize that methylation in the exon
      region may also take part in the down-regulation of the PR gene. The methylation
      status of the first exon of the PR gene in endometrial cell cultures was
      investigated. Aberrant methylation patterns were observed in the first exon of PR
      gene, and the methylation density is correlated with the differentiation of
      different types of endometrial cancer cells. DNA methyltransferase (DNMT) and
      histone deacetylase inhibitor 5-aza-2'-deoxycytidine (ADC), as well as
      trichostatin A (TSA), which reverses PR gene expression, were also studied. A
      combination of ADC and TSA resulted in synergistic effects in inducing PR
      expression, down-regulation of DNMT1 and DNMT3A, and could also have antigrowth
      effect on endometrial cancer cells by inducing apoptosis.

PMID- 17556067
TI  - Prognostic significance of cytogenetically detected chromosome 21 anomalies in
      childhood acute lymphoblastic leukemia: a Pediatric Oncology Group study.
AB  - Chromosome anomalies have been shown to have prognostic significance in children
      with acute lymphoblastic leukemia (ALL). Chromosome 21 was evaluated for its
      ability to predict outcome when found in either a single copy (the Mono21 group)
      or when involved in a structural aberration (the Misc21 group). Both anomalies
      were associated with an increased risk of failure for patients with standard-risk
      ALL, rather than higher-risk ALL. Event-free survival was 50.0% at 5 years and
      48.4% at 8 years for standard-risk patients with Mono21+Misc21, compared with
      77.8 and 75.5%, respectively, for standard-risk patients without these anomalies
      of chromosome 21. There was no significant difference in outcome between the
      Mono21 and the Misc21 group (P = 0.10). Mono21 and Misc21 were determined to be
      independently prognostic whether or not the primary leukemic clone had fewer than
      45 chromosomes. The frequency of an adverse outcome was comparable to other poor
      prognosis subgroups such as hypodiploidy (<45 chromosomes), t(9;22), or t(4;11),
      all of which have been targeted for aggressive therapy even if the case is
      otherwise standard risk.

PMID- 17556068
TI  - Evaluation of chromosome 5 aberrations in complex karyotypes of patients with
      myeloid disorders reveals their contribution to dicentric and tricentric
      chromosomes, resulting in the loss of critical 5q regions.
AB  - Dicentric chromosomes have often been observed in complex karyotypes in
      previously reported studies of therapy-related myelodysplastic syndromes (MDS)
      and acute myeloid leukemia (AML). Fluorescence in situ hybridization (FISH) has
      now made the characterization of these rearrangements much easier. Dicentric and
      tricentric chromosomes were identified in 21 patients (9 MDS and 12 AML) among
      the 133 consecutive MDS/AML patients (17%) who had a structural or numerical
      aberration of chromosome 5 using conventional cytogenetic analysis. One third
      (7/21) of the patients had received alkylating drugs for a previously diagnosed
      cancer or chronic myeloproliferative disease. Loss of 5q material was identified
      in all 21 patients. One copy of the EGR1 (5q31) or the CSF1R (5q33 approximately
      q34) genes was lost in 20 of the 21 patients. Dicentric and tricentric
      chromosomes involving chromosome 5 are frequently observed in complex karyotypes
      among patients with de novo or therapy-related MDS/AML. They lead to deletions of
      various parts of the long arm of chromosome 5.

PMID- 17556069
TI  - Physical status of multiple human papillomavirus genotypes in flow-sorted
      cervical cancer cells.
AB  - Multiple human papilloma virus (HPV) infections have been detected in cervical
      cancer. To investigate the significance of multiple HPV infections, we studied
      their prevalence in cancer samples from a low-risk (Dutch) and a high-risk
      (Surinamese) population and the correlation of HPV infection with tumor cell
      aneuploidy. SPF(10) LiPA was used for HPV detection in formalin-fixed cervical
      carcinoma samples from 96 Dutch and 95 Surinamese patients. Samples with HPV type
      16 or 18 infections were sorted by flow cytometry, and fluorescence in situ
      hybridization was performed on the diploid and aneuploid subpopulations to detect
      HPV 16 and 18 genotypes simultaneously. Multiple HPV infections were present in
      11 of 80 (13.8%) Dutch and 17 of 77 (22.1%) Surinamese carcinomas. Three cases
      had an HPV 16 and HPV 18 coinfection: in two cases, integrated HPV copies of HPV
      16 or 18 were detected in the aneuploid fraction, and in one case both HPV 16 and
      18 were present solely as episomes. Based on our findings, multiple HPV
      infections are present in cervical cancer samples from both high- and low-risk
      populations. Furthermore, multiple HPV types can be present in an episomal state
      in both diploid and aneuploid tumor cells, but integrated HPV genomes are
      detectable only in the aneuploid tumor cell subpopulations.

PMID- 17556070
TI  - Frequent chromosomal gains in recurrent juvenile nasopharyngeal angiofibroma.
AB  - Juvenile nasopharyngeal angiofibroma (JNA) is a rare benign tumor, mostly
      affecting adolescent males. Some patients develop recurrences after surgery
      independently of completeness of removal. Only very limited data concerning
      underlying chromosomal changes are available. We therefore analyzed samples of 22
      JNAs, including six recurrences, with comparative genomic hybridization (CGH).
      Additionally, quantitative image cytometry was used for measurement of DNA
      aneuploidy in representative samples. Of the 13 primary JNAs without later
      recurrence, DNA gains were identified on autosomes in only two samples. Four
      patients with one or two recurrences were included in the study; for one of
      these, no material of the primary tumor was available for analysis. Looking at
      autosomes, two of the three available primaries displayed multiple gains; in one
      of those, two additional losses were observed. Multiple gains were detected in
      two of the four first recurrences, but none in the two second recurrences. Across
      all 22 samples, gains occurred in more than one sample on chromosomes arms 1p,
      9q, 10q, 12q, 16p, 16q, 17q, 19p, 19q, 20q, and 22q. Losses were found in a
      single case exclusively on chromosome 4. Sex chromosomes were frequently affected
      in both primary tumors and recurrences. There was no correlation among tumor
      staging, age, and DNA amplification. No DNA aneuploidy was detected, a finding in
      accordance with the generally benign characteristics of JNAs. Our observations
      suggest that in JNA the activation of oncogenes is more likely than the
      inactivation of tumor suppressor genes. Autosomal gains in the primary tumor
      should be further evaluated as markers for a potentially increased risk of
      recurrence after surgical removal in this entity.

PMID- 17556071
TI  - Optimization of comparative expressed sequence hybridization for genome-wide
      expression profiling at chromosome level.
AB  - Comparative expressed sequence hybridization (CESH) has recently been developed
      for global expression profiling at chromosome level. To improve its specificity
      and sensitivity, we examined the effects of cDNA amplification and labeling
      methods on CESH profiles, using a gastric cancer cell line, Kato III, and
      compared the CESH profiles to cDNA microarray and reverse transcriptase
      polymerase chain reaction (RT-PCR) data. CESH results were scarcely affected by
      the amplification process, either at the RNA level with T7 polymerase or at the
      cDNA level with degenerate oligonucleotide-primed PCR (DOP-PCR). The labeling
      method, however, did remarkably affect the CESH results; false positive shifts of
      the test/reference ratio (T/R) were not detected in self-matched CESH with pre
      cDNA labeling and random priming labeling of cDNA but were consistently seen with
      DOP-PCR labeling in 11 chromosomes. The use of cDNA deriving from mRNA either
      with pre-cDNA or random priming labeling gave results of higher detection
      sensitivity for regions of up- or downregulated expression and higher concordance
      with the microarray and RT-PCR data in the corresponding regions than with
      conventional CESH. This modification of CESH with random priming labeling was
      found feasible by its application to Kato III cells with and without 5-aza-2'
      deoxycytidine treatment; the regions identified as epigenetically silenced
      included genes that were reportedly methylated in Kato III.

PMID- 17556072
TI  - Variant t(2;11)(p11.2;q13) without IGK involvement in a case of mantle cell
      lymphoma.
AB  - Mantle cell lymphoma (MCL) is characterized by the t(11;14)(q13;q32)
      translocation, which leads to overexpression of the cyclin D1 (CCND1) gene. This
      translocation is observed in almost all cases of MCL. In this alteration, the
      involvement of immunoglobulin heavy chain (IGH) locus plays a key role in the
      activation of the CCND1 oncogene. Translocations affecting IGH loci are mostly
      prevalent in B-cell lymphomas, but variant translocations involving
      immunoglobulin kappa (IGK) or lambda (IGL) light chain loci have been observed in
      a minority of B-lymphoid malignancies. Variant translocations have been reported
      in only a few cases of MCL, however. This report presents a case of MCL with a
      variant t(2;11)(p11.2;q13), rearrangement of the CCND1 gene, and overexpression
      of cyclin D1. To characterize this rearrangement, specific noncommercial probes
      were used. This set of probes comprises IGK and REL flanking probes and 12
      bacterial artificial chromosome (BAC) probes covering the region to be
      investigated. The results indicated that this alteration has not affected the IGK
      locus, and the breakpoint was within a 260-kb region located approximately 1 Mb
      telomerically to the IGK gene. It is probable that the KV3J gene localized in
      this region could deregulate the expression of cyclin D1.

PMID- 17556073
TI  - Detailed characterization of 7q deletions by multicolor banding (mBAND) in
      marginal zone cell lymphoma.
AB  - High-resolution multicolor banding (mBAND) analysis was applied to precisely fine
      map the genomic extent of 7q deletions in a series of 26 marginal zone lymphoma
      patients displaying the abnormality on conventional karyotypes. Using this
      approach, the breakpoints and the extent of deletions revealed by conventional
      banding techniques had to be re-defined in 70% of cases. Although no common
      minimal region of deletion was delineated, mBAND demonstrated the involvement of
      the 7q32 region in more than 90% of cases. In addition, unsuspected
      translocations and intrachromosomal changes could be identified in four cases.
      Taken together, these data demonstrate that mBAND represents an alternative
      cytogenetic tool in the comprehensive analysis of chromosome aberrations in
      hematologic malignancies, allowing rapid screening and precise delineation of
      structural rearrangements of a defined chromosome. This also confirms the
      localization in the vicinity of band 7q32 of putative candidate gene(s) involved
      in the pathogenic development of the disease.

PMID- 17556074
TI  - Incidence of submicroscopic deletions vary according to disease entities and
      chromosomal translocations in hematologic malignancies: investigation by
      fluorescence in situ hybridization.
AB  - Submicroscopic deletions of genes in recurrent chromosomal rearrangements occur
      frequently in hematologic malignancies, but their incidences have not been
      reported clearly. We investigated the incidence of submicroscopic deletions and
      their association with specific genetic rearrangements in various hematologic
      malignancies. A fluorescence in situ hybridization (FISH) study was conducted in
      336 patients with acute lymphoblastic leukemia, 223 patients with acute myeloid
      leukemia, and 79 patients with chronic myelogenous leukemia. The incidence of
      submicroscopic deletions in patients with chromosomal rearrangements was the
      highest in the TEL/AML1 rearrangement (65.0%), followed by BCR/ABL (10.9%), MLL
      (5.6%), AML/ETO (4.0%), and PML/RARA (0.0%). Submicroscopic deletion was quite
      common, and incidences were variable according to disease entities and
      chromosomal translocations. To detect submicroscopic deletions, careful FISH
      study should be included for the cytogenetic study of hematologic malignancies,
      and their association with clinical prognosis needs to be further studied.

PMID- 17556075
TI  - Comparative genomic hybridization reveals frequent losses of 1p and 3q in benign
      pheochromocytomas of Japanese patients.

PMID- 17556076
TI  - km23, a transforming growth factor-beta signaling component, is infrequently
      mutated in human colorectal and gastric cancers.

PMID- 17556077
TI  - Trisomy 8 in chronic lymphocytic leukemia: a report of two cases.

PMID- 17556078
TI  - Deletion 9q in a patient with concomitant myelodysplasia and non-Hodgkin
      lymphoma.

PMID- 17556082
TI  - The goals of resident training in laboratory medicine in combined anatomic
      pathology/clinical pathology programs: an overview.
AB  - Training of residents in the discipline of laboratory medicine is confounded by
      the diversity of the subdisciplines of clinical pathology each with specific
      knowledge sets, and the career goals of the residents who are focused on
      different aspects of clinical pathology. What guides this training is not the
      detailed knowledge sets or the specific technologies per se, but a focus on the
      principles that undergird all of laboratory medicine. Thus, the goal of clinical
      pathology training is to develop a clinical consultant who can apply laboratory
      derived, population-based clinical data and laboratory-based therapeutics, along
      with a firm knowledge of the underlying biotechnology from which these are
      derived, to the benefit of individual patients. Furthermore, this pathologist
      must be steeped in the skills required for lifelong learning and adaptation.

PMID- 17556083
TI  - Proposed research training guidelines for residents in laboratory medicine.
AB  - It is expected that the role of the clinical pathologist will evolve from the
      more passive role of managing testing facilities to one of active service
      provider, using powerful molecular, cell biologic, and biochemical tools. The
      scope of knowledge required to be an effective physician scientist or an
      accomplished practicing clinical pathologist, however, cannot be acquired through
      clinical training alone and requires dedicated, structured research learning
      time. The goal of this article is to consider mechanisms that effectively
      integrate research training and scholarly activity into residency education in
      laboratory medicine/clinical pathology. The proposed curricula are purposely
      unstructured to allow maximum flexibility for training programs to meet the needs
      and career goals of individual residents.

PMID- 17556084
TI  - Innovative methods in laboratory medicine resident teaching.
AB  - Many methodologies have been employed in training laboratory medicine (clinical
      pathology) residents. Apprenticeship activities (observing and reproducing the
      job of an attending clinical pathologist in a direct practice setting) likely
      remain the most popular for trainees and arguably one of the most effective. The
      utility and current status of morning report, journal club, resident-led-grand
      rounds style presentations, faculty didactics, research by residents, placing
      residents specifically in the role of teachers themselves, hands-on activities in
      clinical laboratories, and emerging computer-based learning modalities are
      compared with each other and to similar exercises in other medical disciplines.

PMID- 17556080
TI  - Roles of dynamic and reversible histone acetylation in plant development and
      polyploidy.
AB  - Transcriptional regulation in eukaryotes is not simply determined by the DNA
      sequence, but rather mediated through dynamic chromatin modifications and
      remodeling. Recent studies have shown that reversible and rapid changes in
      histone acetylation play an essential role in chromatin modification, induce
      genome-wide and specific changes in gene expression, and affect a variety of
      biological processes in response to internal and external signals, such as cell
      differentiation, growth, development, light, temperature, and abiotic and biotic
      stresses. Moreover, histone acetylation and deacetylation are associated with RNA
      interference and other chromatin modifications including DNA and histone
      methylation. The reversible changes in histone acetylation also contribute to
      cell cycle regulation and epigenetic silencing of rDNA and redundant genes in
      response to interspecific hybridization and polyploidy.

PMID- 17556085
TI  - Assessing resident competency in laboratory medicine.
AB  - Validation of the competence of laboratory medicine (LM) residents for
      independent practice and to sit for the examination in clinical pathology rests
      with the program director. Assessing knowledge and basic skills were the primary
      measure of residents until 2000. The Accreditation Council of Graduate Medical
      Education and the ABMS launched the Outcome Project in 2000 as a response to the
      public. A shift in emphasis from "process" to a more "outcomes driven" assessment
      came with the Outcome Project. As of July 2006, the training of LM residents must
      incorporate the six competencies of the Outcome Project within each resident
      experience (rotation). In this article, comparison of historic and current
      methods of assessing residents is noted. Current and future outcomes and the
      pivotal role of consultation in LM are noted.

PMID- 17556086
TI  - The American Society for Clinical Pathology resident in-service examination: does
      resident performance provide insight into the effectiveness of clinical pathology
      education?
AB  - The resident in-service examination in pathology is an in-training exercise that
      is taken by virtually all pathology residents in the United States as well as by
      some participants in Canada, Ireland, and Lebanon. Although all of the anatomic
      pathology topics in the examination, with only one exception-forensic pathology,
      show significant improvement in scores over the 4 years of residency training,
      three areas of clinical pathology training (laboratory administration, clinical
      chemistry, and microbiology) show significantly lower improvement in performance
      over the years of residency training. By contrast, transfusion medicine,
      hematopathology and the special topics section of the examination all demonstrate
      improved performance by residents over time. While the reason behind these
      differences must remain speculative at this time, these findings suggest that
      measures to improve effectiveness in clinical pathology training might be
      suggested by examining the differences between residency training practices
      between higher and lower performing areas of clinical pathology.

PMID- 17556087
TI  - Resident and fellow training in transfusion medicine.
AB  - This article focuses on the design of transfusion medicine residency and
      fellowship training programs in the context of the Accreditation Commission for
      Graduate Medical Education (ACGME) competencies. Transfusion-specific examples of
      the six ACGME competencies are discussed, a transfusion medicine curriculum with
      designated training stages for specific curriculum elements is proposed, and
      examples of training activities are given. The authors also discuss transfusion
      service rotation design and how to build in graduated responsibility as training
      proceeds. Finally, methods for assessing the competency of transfusion medicine
      trainees and the effectiveness of the training program and teaching faculty are
      described. It is hoped that this article will provide a blueprint for how to
      design and implement a successful transfusion medicine residency and fellowship
      training program.

PMID- 17556088
TI  - Resident training in clinical chemistry.
AB  - Practicing clinical chemists responded to an anonymous, open-ended questionnaire
      designed to define the state of clinical chemistry education in pathology
      training programs in the United States. Survey respondents identified many ideas
      for educational improvements and offered criticism regarding aspects of clinical
      chemistry education that are not working particularly well. Many of these
      findings are generalizable to other subspecialties of clinical pathology. It is
      hoped that this analysis will allow readers to compare their programs with
      national trends and identify new ways of improving clinical chemistry training at
      their institutions.

PMID- 17556089
TI  - Resident training in laboratory hematology.
AB  - The authors of this article formulate a strategy to guide residents and faculty
      in laboratory hematology. The authors build upon the recommendations of the
      Academy of Clinical Laboratory Physicians and Scientists (ACLPS) published
      earlier as well as draw from their own experiences, in discussing principles that
      should be considered when implementing a program that effectively trains
      residents to be competent pathologists in the various settings that they may
      encounter once they complete training.

PMID- 17556090
TI  - Resident training in microbiology.
AB  - To meet the challenges of diagnosis and management of infectious diseases,
      clinical pathology residents must receive comprehensive training in microbiology,
      learn to think critically, develop problem-solving skills, and take active roles
      as laboratory consultants. Residents well trained in clinical microbiology become
      capable laboratory professionals, developing cost-effective testing strategies,
      decreasing risk for medical errors, and improving patient care. Newer methods for
      diagnosing infectious disease, such as real-time polymerase chain reaction,
      microarrays for pathogen detection, and rapid assays for antigen or antibody
      detection, have become standard. Knowledge of infectious disease principles, drug
      therapeutic options, and drug resistance is also important. Suggestions for
      training and for assessing resident competency in clinical microbiology are
      presented.

PMID- 17556091
TI  - Training in laboratory management and the MBA/MD in laboratory medicine.
AB  - The business of medicine requires more than just the knowledge and skills
      necessary to provide quality patient care. A growing number of opportunities are
      available for physicians to learn how to better manage the business side of their
      practices. Today's clinical laboratories, particularly those in health care
      organizations under pressure to efficiently use limited resources, benefit from
      having management and leadership specifically trained for these roles.

PMID- 17556092
TI  - Resident training in point-of-care testing.
AB  - Although central laboratory testing has been the norm for the last few decades
      and point-of-care testing (POCT) is considered an emerging area, physicians were
      performing POCT long before the existence of central laboratory testing. As
      medical directors of POCT programs, pathologists need the basic knowledge and
      skills associated with directing laboratory-based testing programs as well as
      additional knowledge and skills about testing at the point of care. Although the
      essential elements of quality testing are the same for laboratory-based and POCT,
      the enormous variety of settings, technologies, and workers involved present
      unique challenges.

PMID- 17556093
TI  - Teaching medical students basic principles of laboratory medicine.
AB  - Laboratory medicine is a distinct medical discipline and a tool for patient care
      that is used in all specialties. It is based on underlying concepts that govern
      the proper use and interpretation of laboratory tests. This article suggests how
      to educate medical students about important preanalytic, analytic, and
      postanalytic variables that affect laboratory results. The authors postulate that
      laboratory medicine training requires a combination of focused lectures and a
      constant reinforcement of its principles throughout clinical rotations.

PMID- 17556094
TI  - The MD/PhD pathway to a career in laboratory medicine.
AB  - Laboratory medicine offers attractive opportunities for individuals who have MD
      and PhD degrees and advanced training in medicine and the underlying basic
      biomedical sciences, and these individuals have much to contribute to the field.
      The modern era of basic biomedical sciences has produced a wealth of genomic,
      postgenomic, and proteomic knowledge. As a bridge discipline, a major challenge
      and opportunity for laboratory medicine is to bring these advances to the
      diagnostic, prognostic, and therapeutic care of patients. The authors believe
      that, for many reasons, the field of laboratory medicine represents an excellent,
      although underrecognized, career choice for graduates of MD/PhD programs.

PMID- 17556095
TI  - Education of the PhD in laboratory medicine.
AB  - Throughout the history of laboratory medicine, the PhD scientist has played a
      role in developing new methods and algorithms that have contributed significantly
      to the field. Although the number of formally trained PhDs in laboratory medicine
      is currently small, they continue to play an important role in large, primarily
      academic, clinical laboratories and departments and in the in vitro diagnostics
      industry. This article discusses the importance of the formally trained PhD in
      today's laboratory medicine environment and the necessary training process, and
      approach for training PhDs at the postdoctoral level to have successful careers
      in laboratory medicine.

PMID- 17556096
TI  - Proprotein convertases 1 and 2 (PC1 and PC2) are expressed in neurally
      differentiated rat bone marrow stromal stem cells (BMSCs).
AB  - Neural-like cells derived from bone marrow stromal stem cells (BMSCs) have
      potential usefulness in cell therapy of degenerative or traumatic diseases of the
      central nervous system (CNS). The functional recovery mediated by these cells,
      however, depends on the secretion of neurotrophins (NTs) and their cognate
      receptors, as the main regulators of neural survival and death. The function of
      NTs is further modulated by proprotein convertase (PC) enzymes which function in
      converting proproteins (including proNTs) into their functional end products.
      Accordingly, failure in converting proprotein forms of NTs into their mature
      forms may lead to neuronal cell death. In the present study, we have investigated
      the expression profile of PCs before and during neural differentiation of rat
      BMSCs by RT-PCR. Our results show that major members of the PC family functioning
      in the constitutive secretory pathway (furin, PACE4 and PC7/LPC) are highly
      expressed in both undifferentiated and neurally differentiated BMSCs. In
      contrast, while PC1/PC3 and PC2 (specific to neural and endocrine cells) are
      absent in undifferentiated BMSCs, their expression is initiated upon the
      induction of differentiation. In conclusion, our results suggest that neurally
      differentiated BMSCs have acquired the functional machinery to process the
      precursor forms of proteins in both the constitutive and regulated pathways.

PMID- 17556098
TI  - The effect of selective attention on the gamma-band auditory steady-state
      response.
AB  - Studies have demonstrated that selective attention can modulate the steady-state
      evoked potential to repetitive visual and tactile stimulation. However,
      examinations of the effect of attention on the auditory steady-state response
      (ASSR) have proven equivocal. The current experiment therefore utilized EEG to
      examine the effect of attention on the ASSR in healthy humans (n=15). Auditory
      click trains in the beta (20 Hz) and gamma (40 Hz) ranges were randomly presented
      binaurally in an oddball discrimination paradigm (each frequency served as the
      oddball (target) in each of two blocks). A Fast Fourier Transform was used to
      assess the effect of attention on the ASSR (signal power), and phase consistency
      across trials was assessed using the phase-locking factor (PLF). As expected,
      both 20 and 40 Hz targets elicited a robust P300 response, with maximal
      amplitudes over parietal regions. For the ASSR, it was found that EEG signal
      power was larger to 40 Hz targets compared to 40 Hz frequent stimuli across all
      frontocentral electrodes. No differences in signal power were observed during 20
      Hz stimulation. Finally, increased PLF values were observed for 40 Hz targets
      compared to frequent trials. These results provide evidence that selective
      attention can enhance signal power and phase-locking of the ASSR, particularly to
      auditory stimulation in the gamma range.

PMID- 17556097
TI  - Signal transduction pathways of GM-CSF in neural cell lines.
AB  - GM-CSF is recently being suggested to play important role(s) in the nervous
      system. Present study was intended to understand signal transduction pathways of
      GM-CSF in human neuroblastoma (SK-N-(BE)2) and glioblastoma (A172) cell lines.
      The expression of GM-CSF receptors on the surface of these cells was confirmed by
      immunocytochemistry, Western blot analysis and RT-PCR. When treated for 10min, GM
      CSF activated the signal transducer and activator of transcription 5 (STAT5) and
      extracellular signal regulated kinase (ERK) in both cell lines. However, Janus
      kinase 2 (JAK2) was activated only in A172 cells but not in SK-N-(BE)2 cells by
      GM-CSF. The GM-CSF-activated cellular signal pathways were specifically inhibited
      by the pretreatment of GM-CSF receptor alpha antibody, suggesting the specificity
      of the signal activation. The experiment using specific inhibitors (AG490) to the
      JAK/STAT pathway showed that JAK2/STAT5 cascade was well preserved and activated
      by GM-CSF in A172 cells, while STAT5 was activated by GM-CSF without JAK2
      activation in SK-N-(EB)2 cells. The ERK pathway was activated by GM-CSF
      independently of JAK2 in both cell lines. Finally, GM-CSF showed cytoprotective
      effect on these cell lines by inhibiting cytotoxicity of saturosporine. The
      results revealed the signal transduction pathways activated by GM-CSF in neural
      cells and suggested that GM-CSF might affect the neural functions via these
      signal pathways.

PMID- 17556099
TI  - Beta-synuclein gene variants and Parkinson's disease: a preliminary case-control
      study.
AB  - Aggregation and fibrillization of the alpha-synuclein protein, which is the main
      component of Lewy bodies, may represent important processes in the pathogenesis
      of Parkinson's disease (PD). Several in vivo and in vitro studies suggest that
      beta-synuclein may be a natural negative regulator of alpha-synuclein aggregation
      and fibrillization. The goal of the present study was to investigate the
      association of two polymorphisms (rs35035889 and rs1352303) in the beta-synuclein
      (SNCB) gene with PD. Our case-control study included a total of 370 case
      unaffected sibling pairs and 168 case-unrelated control pairs (538 pairs total).
      The subjects were recruited from an ongoing study of the molecular epidemiology
      of PD in the Upper Midwest (USA). We employed a liberalization of the sibling
      transmission disequilibrium test to study the main effects of the gene variants
      for subjects overall and for strata defined by age at study, gender, ethnicity,
      clinical diagnostic certainty, dementia, and family history of PD (adjusted for
      age at study and gender as appropriate). The analyses were conducted for each
      SNCB variant separately, and also for two-locus haplotypes using score tests.
      Neither of the SNCB SNPs examined were associated with PD overall or in strata,
      and haplotype analyses were negative as well. However, one of the two SNPs
      (rs1352303) was associated with a delayed age at onset of PD in women. The
      results of this preliminary study suggest that the SNCB locus, though not a
      susceptibility gene for PD, might modify the age at onset of PD.

PMID- 17556100
TI  - PP2, a potent inhibitor of Src family kinases, protects against hippocampal CA1
      pyramidal cell death after transient global brain ischemia.
AB  - It has been indicated that Src family protein tyrosine kinases (SrcPTKs)
      potentiate N-methyl-D-aspartate (NMDA) receptor function by phosphorylating NR2A
      subunits and that postsynaptic density protein 95 (PSD-95) facilitates this
      regulation. In this paper, we define the role of SrcPTKs in delayed neuronal
      damage following transient brain ischemia and explore the underlying mechanisms
      involved in this event. Transient global brain ischemia was induced by the four
      vessel occlusion method. A specific Src family kinase inhibitor PP2 (4-amino-5-(4
      chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyramidine) and a PP2 negative control
      PP3 (4-amino-7-phenylpyrazolo[3,4-d]pyramidine) were infused into rat
      cerebroventricule 30 min before occlusion. Hematoxylin and eosine staining showed
      that the number of surviving pyramidal neurons in rat hippocampal CA1 subfield
      increased markedly in PP2-treated rats comparing to PP3-treated groups after 5
      days of reperfusion following ischemia. Additionally, immunoprecipitation and
      immunoblot analysis revealed that preadministration of PP2, but not PP3,
      attenuated not only the increased tyrosine phosphorylation of NR2A but also the
      enhanced interactions among Src, NR2A and PSD-95 induced by ischemia/reperfusion.
      In conclusion, SrcPTKs promote binding of the kinases and their substrate NR2A
      attributed to the scaffolding effect of PSD-95 during transient brain ischemia
      and reperfusion, which are responsible for the elevation of NR2A tyrosine
      phosphorylation and consequent delayed neuronal cell death.

PMID- 17556101
TI  - Event-related potential study to aversive auditory stimuli.
AB  - In an auditory oddball task emotionally negative (aversive) sounds (e.g. rubbing
      together of polystyrene) and everyday sounds (e.g. ringing of a bicycle bell)
      were presented as task-irrelevant (novel) sounds. Both the aversive and the
      everyday sounds elicited the orientation-related P3a component of the event
      related potentials (ERPs). In the 154-250 ms range the ERPs for the aversive
      sounds were more negative than the ERP of the everyday sounds. For the aversive
      sounds, this negativity was followed by a frontal positive wave (372-456 ms). The
      aversive sounds elicited larger late positive shift than the everyday sounds. The
      early negativity is considered as an initial effect in a broad neural network
      including limbic structures, while the later is related to the cognitive
      assessment of the stimuli and to memory-related processes.

PMID- 17556102
TI  - Decreased levels of serum nitric oxide in different forms of dementia.
AB  - Nitric oxide is involved in normal physiological functions and also in
      pathological processes leading to tissue damage due, in part, to its free radical
      nature (oxidative stress). Oxidative stress and vascular dysfunction have been
      recognized as contributing factors in the pathogenesis of Alzheimer disease (AD)
      and vascular dementia (VD). In order to study the possible links between these
      processes and dementia, we have analysed plasma amyloid-beta(1-42) levels (Abeta)
      and total nitric oxide (NOx), apolipoprotein E (ApoE), lipids, vitamin B12, and
      folate concentrations in the serum of 99 patients with dementia and 55 age
      matched non-demented controls. Both nitrate and nitrite levels were measured by a
      colorimetric method using Griess Reagent and plasma Abeta levels were analysed by
      a hypersensitive ELISA method. Our data showed a significant decrease of serum
      NOx levels in dementia, especially in probable AD and VD patients, as compared
      with controls. We observed a weak correlation between serum NOx levels and
      cognitive deterioration in dementia; however, NOx levels were not associated with
      ApoE and Abeta levels. In dementia and controls, a similar correlation pattern
      between HDL-cholesterol versus NOx was found. No apparent association between
      NOx, Abeta and AD-related genes [APOE (apolipoprotein E), PSEN1 (Presenilin 1)]
      was observed. Our data suggest that NOx may contribute to the pathogenesis of
      dementia through a process mediated by HDL-cholesterol.

PMID- 17556103
TI  - Changes in BDNF gene expression correlate with rat strain differences in
      neuropathic pain.
AB  - The Fischer 344 (F344) rat inbred strain differs from the inbred Lewis and the
      outbred Sprague-Dawley (SD) in the response to different pain stimuli, which has
      been partially attributed to differences in the endogenous opioid and
      noradrenergic systems. Since brain-derived neutrophic factor (BDNF) modulates
      both the endogenous opioid and noradrenergic systems, we have now studied
      specific changes in BDNF gene expression related to the maintenance of
      neuropathic pain in the three rat strains. F344 rats were found to be the only
      strain that completely recovered from neuropathic pain (mechanical allodynia) 28
      days after chronic constriction injury (CCI) of the sciatic nerve. Real time RT
      PCR studies revealed minimal changes in the expression of BDNF in the spinal cord
      after CCI despite the strain considered, but marked changes in dorsal root
      ganglia (DRG) were observed. A significant upregulation of BDNF gene expression
      was found only in injured DRG of F344 rats, thus correlating with higher
      resistance to neuropathic pain. The data suggest that BDNF could be involved in
      strain differences concerning CCI resistance.

PMID- 17556104
TI  - Morality and mental illness.

PMID- 17556105
TI  - Employment through residency programs: a strategy to address the workforce crisis
      in psychiatric nursing.
AB  - Australia, like most countries in the world, is facing a crisis regarding the
      recruitment and retention of nurses. This situation is particularly notable for
      psychiatric nursing, a specialty not generally popular among undergraduate
      nursing students. To date, the nursing literature has tended to identify the
      problem, with less attention to the exploration of possible solutions. The aim of
      this article is to explore the literature concerning residency programs for
      nursing students. Although limited, the literature suggests potential benefits to
      this program, including improvements in competency and confidence, resulting in
      reduced need for lengthy orientation for new graduates and overall improvements
      in recruitment and retention rates for psychiatric nurses. In conclusion,
      residency programs for undergraduate nursing students could provide a useful
      strategy to improve the image of psychiatric nursing and attract new graduates.
      Further research is required to assess the applicability of this model in
      Australia.

PMID- 17556106
TI  - Effects of a bereavement intervention program in middle-aged widows in Korea.
AB  - Dan-jeon is a meditative practice composed of both breathing and stretching
      exercises causing life energies to circulate blood throughout the body. Following
      a bereavement intervention program composed of Dan-jeon breathing sessions, a
      self-help group activity, and a health check, an experimental group showed
      significantly greater decrements in grief levels and symptoms of stress over a
      control group who received only a health check. Among the participants, there
      were no significant differences in immune response, percentages of T lymphocytes,
      helper T lymphocytes (Th), suppressor T lymphocytes (Ts), B lymphocytes, natural
      killer cells, monocytes, and Th:Ts ratios.

PMID- 17556107
TI  - The integration of physical health and behavioral health services: three
      university case examples.
AB  - To improve the quality of care, the Institute of Medicine has called for the
      integration of mental health and substance use care with primary care services.
      This article reports three case studies of service integration efforts in
      universities. The results provide support for the feasibility of such
      initiatives. In the three case studies, service integration proved to be both
      clinically and financially feasible.

PMID- 17556108
TI  - Exploring the relationships between depression, hopelessness, cognitive status,
      pain, and spirituality in patients with advanced cancer.
AB  - The growing interest in the psychological morbidity of patients with cancer has
      been the major reason for conducting this study. The measurements used were the
      Beck Depression Inventory, the Beck Hopelessness Scale, the Mini Mental State
      Examination, the Greek Brief Pain Inventory, and the Spiritual Involvement and
      Beliefs Scale. The analysis was conducted in 82 patients with advanced cancer.
      Significant associations were found between pain interference in "mood" and in
      "enjoyment of life" and hopelessness, as well as between worse pain and pain
      interference items with depression and cognitive status. Significant correlations
      were found between hopelessness, depression, and cognitive condition. These
      findings demonstrate the physical, psychological, and cognitive aspects of
      patients with cancer.

PMID- 17556109
TI  - Immigrant youth at risk for disorders of mood: recognizing complex dynamics.
AB  - The number of youth immigrating to the United States from Latin America and the
      Caribbean has consistently and dramatically been increasing. However, little
      research or epidemiological data that capture the mental health status of these
      youth from their countries of origin or once they enter the United States exist.
      As a result of migration and the acculturation process, these youth are at risk
      for exacerbation of preexisting mood disorders or development of mood or other
      psychiatric symptoms. Pre-migration social and environmental stressors affecting
      this population include poverty, exposure to violence, sexual or physical
      victimization, and substance abuse. Post-migration stressors include loss (of
      friends, family, country, and lifestyle), changes in social support, negative
      experiences in the United States, language difficulties, and academic challenges.
      This review of the existing literature will describe the contextual experiences
      of immigrant Latin American and Caribbean youth from their country of origin and
      as new immigrants in the United States, discuss their risk for mood disorders,
      highlight relevant assessment data that should be obtained, and identify
      treatment implications for advanced practice psychiatric-mental health nurses
      working with this population.

PMID- 17556110
TI  - The recovery movement: defining evidence-based processes.

PMID- 17556111
TI  - The health of the staff is as important as the health of the people we serve.

PMID- 17556112
TI  - Horizontal violence among nursing students.
AB  - In a research study student nurses in the clinical setting reported experiencing
      horizontal violence or "nurses eating their young." The types of behaviors most
      frequently encountered were emotional and verbal attacks. Some students did not
      report incidences of horizontal violence to their instructors, so it is important
      that the faculty be cognizant that such behaviors can occur and establish open
      communication to assist students in dealing with such behaviors.

PMID- 17556113
TI  - From memory-based decisions to decision-based movements: a model of interval
      discrimination followed by action selection.
AB  - The interval discrimination task is a classical experimental paradigm that is
      employed to study working memory and decision making and typically involves four
      phases. First, the subject receives a stimulus, then holds it in the working
      memory, then makes a decision by comparing it with another stimulus and finally
      acts on this decision, usually by pressing one of the two buttons corresponding
      to the binary decision. This article demonstrates that simple linear readouts
      from generic neural microcircuits that send feedback of their activity to the
      circuit, can be trained using identical learning mechanisms to perform quite
      separate tasks of decision making and generation of subsequent motor commands. In
      this sense, the neurocomputational algorithm presented here is able to integrate
      the four computational stages into a single unified framework. The algorithm is
      tested using two-interval discrimination and delayed-match-to-sample experimental
      paradigms as benchmarks.

PMID- 17556114
TI  - Fading memory and time series prediction in recurrent networks with different
      forms of plasticity.
AB  - We investigate how different forms of plasticity shape the dynamics and
      computational properties of simple recurrent spiking neural networks. In
      particular, we study the effect of combining two forms of neuronal plasticity:
      spike timing dependent plasticity (STDP), which changes the synaptic strength,
      and intrinsic plasticity (IP), which changes the excitability of individual
      neurons to maintain homeostasis of their activity. We find that the interaction
      of these forms of plasticity gives rise to interesting network dynamics
      characterized by a comparatively large number of stable limit cycles. We study
      the response of such networks to external input and find that they exhibit a
      fading memory of recent inputs. We then demonstrate that the combination of STDP
      and IP shapes the network structure and dynamics in ways that allow the discovery
      of patterns in input time series and lead to good performance in time series
      prediction. Our results underscore the importance of studying the interaction of
      different forms of plasticity on network behavior.

PMID- 17556115
TI  - Automatic speech recognition using a predictive echo state network classifier.
AB  - We have combined an echo state network (ESN) with a competitive state machine
      framework to create a classification engine called the predictive ESN classifier.
      We derive the expressions for training the predictive ESN classifier and show
      that the model was significantly more noise robust compared to a hidden Markov
      model in noisy speech classification experiments by 8+/-1 dB signal-to-noise
      ratio. The simple training algorithm and noise robustness of the predictive ESN
      classifier make it an attractive classification engine for automatic speech
      recognition.

PMID- 17556116
TI  - Learning grammatical structure with Echo State Networks.
AB  - Echo State Networks (ESNs) have been shown to be effective for a number of tasks,
      including motor control, dynamic time series prediction, and memorizing musical
      sequences. However, their performance on natural language tasks has been largely
      unexplored until now. Simple Recurrent Networks (SRNs) have a long history in
      language modeling and show a striking similarity in architecture to ESNs. A
      comparison of SRNs and ESNs on a natural language task is therefore a natural
      choice for experimentation. Elman applies SRNs to a standard task in statistical
      NLP: predicting the next word in a corpus, given the previous words. Using a
      simple context-free grammar and an SRN with backpropagation through time (BPTT),
      Elman showed that the network was able to learn internal representations that
      were sensitive to linguistic processes that were useful for the prediction task.
      Here, using ESNs, we show that training such internal representations is
      unnecessary to achieve levels of performance comparable to SRNs. We also compare
      the processing capabilities of ESNs to bigrams and trigrams. Due to some
      unexpected regularities of Elman's grammar, these statistical techniques are
      capable of maintaining dependencies over greater distances than might be
      initially expected. However, we show that the memory of ESNs in this word
      prediction task, although noisy, extends significantly beyond that of bigrams and
      trigrams, enabling ESNs to make good predictions of verb agreement at distances
      over which these methods operate at chance. Overall, our results indicate a
      surprising ability of ESNs to learn a grammar, suggesting that they form useful
      internal representations without learning them.

PMID- 17556117
TI  - Adolescent idiopathic scoliosis: Lenke type I-VI case studies.
AB  - Brace treatment is effective for selected patients with AIS, but when patients
      mature or curves progress beyond 40 degrees , surgery may be discussed with the
      patient and family. The advent of third-generation spinal instrumentation with
      pedicle screw systems has made extraordinary corrections possible. These
      posterior corrections must be done cautiously, however. When selecting the fusion
      level, one should always look at the sagittal plane and include any kyphotic
      segments. The authors evaluate case examples of Lenke type I through type VI
      curves with illustrations and radiographic images in this additional content,
      which is only found on-line.

PMID- 17556119
TI  - The Lenke classification system of operative adolescent idiopathic scoliosis.
AB  - The operative treatment of adolescent idiopathic scoliosis (AIS) is still
      somewhat controversial regarding selection of the appropriate regions to fuse and
      selection of the specific upper instrumented vertebra (UIV) and lowest
      instrumented vertebra (LIV). The Lenke classification system helps to determine
      the appropriate regions of the spine to be fused. The fused regions include the
      major curve and any structural minor curves. After this, the approach, anteriorly
      or, more commonly, posteriorly, and the actual UIV and LIV are selected.
      Ultimately, multicenter studies evaluating large numbers of similar curve
      patterns treated differently should help to sort out the best treatment for each
      particular curve pattern, thus optimizing surgical treatment for patients with
      AIS.

PMID- 17556120
TI  - The Scoliosis Research Society classification for adult spinal deformity.
AB  - The management of adult spinal deformity is characterized by significant
      variability in operative and nonoperative approaches. Adult spinal deformity
      encompasses a broad spectrum of disorders of the spine, and the disparity
      observed in reported clinical outcomes of operative and nonoperative care
      reflects the heterogeneity of the cases studied. A classification of spinal
      deformity in adults is important in providing a framework for comparison of
      similar cases and for reporting outcomes on well-defined disorders. Existing
      classifications of scoliosis are limited in their applicability to adult
      deformity because they do not include parameters of lumbar degenerative change
      and regional sagittal alignment that are critical to decision making in surgical
      care of the adult. The Scoliosis Research Society classification for adult
      deformity is presented in this article. The purpose of this classification is to
      provide a framework for reporting similar cases and to contribute to the
      development of an evidence-based approach to the management of adult spinal
      deformity.

PMID- 17556121
TI  - Radiographic evaluation of spinal deformity.
AB  - A complete radiographic evaluation is inherent in the management of the spinal
      deformity patient; however, a complete evaluation is often not obtained or fully
      appreciated. This article reviews the proper radiographic methodology for
      obtaining consistent reproducible radiographs for spinal deformity. In addition,
      standard radiographic measurements are reviewed, and the reliability and validity
      of these measurements are reported. Regional curve flexibility and end, neutral,
      and stable vertebra selection are also included.

PMID- 17556122
TI  - Correlation of radiographic and clinical findings in spinal deformities.
AB  - Operative treatment for spinal deformities can be undertaken to halt progression
      of deformity or to treat a patient's clinical complaints. New emerging research
      using validated health outcomes instruments has begun to investigate which
      radiographic parameters of spinal deformity correlate with clinical symptoms.
      Adolescent idiopathic scoliosis tends to present without complaints of pain, and
      studies have demonstrated that health-related outcomes measures do not correlate
      with the degree of deformity correction. Clinical complaints in adult scoliosis
      show a poor correlation with curve magnitude. Studies of adult scoliosis
      demonstrate that positive sagittal balance is poorly tolerated and correlates
      with suboptimal health outcomes. Further studies are needed to clarify the
      clinical significance of radiographic features of spinal deformities further.

PMID- 17556123
TI  - Physical examination in adolescent idiopathic scoliosis.
AB  - The following distinguish the physical examination in scoliosis: it is extensive,
      it is revealing, and it influences treatment. Throughout this discussion,
      reference frequently is made to evaluation for underlying neural disease.
      Idiopathic scoliosis is a diagnosis of exclusion, and a neural etiology of spinal
      deformity must be ruled out in every case.

PMID- 17556124
TI  - Low-grade spondylolisthesis.
AB  - Spondylolisthesis is an often painful condition affecting millions of people in
      North America with some ethnic variability. It is characterized by the
      displacement, usually anterior, of on vertebral body upon another. There are
      familial predispositions to having the lesion, and a family history of
      spondylolisthesis may raise one's clinical suspicion. Although the diagnosis is
      easily made on radiographic evaluation, the pathoetiology and appropriate
      treatment modality are not always as clear. In the absence of severe neurological
      symptoms or an unsafe component of instability, a trial of conservative
      management is reasonable and prudent. Nevertheless, surgical management is more
      efficacious for enduring symptomatic relief and restoration of physical function.
      Whereas assessment of postoperative radiographic results lends insight to
      surgical technique, the true barometer of treatment success is improvement in
      patient quality of life.

PMID- 17556125
TI  - Operative management of adult high-grade lumbosacral spondylolisthesis.
AB  - The surgical management of high-grade spondylolisthesis in adults remains
      challenging and controversial. Symptomatic patients often present with severe
      pain, neurologic deficits, or deformity. Although there are several surgical
      options, the decision to proceed with decompression and fusion depends on the
      patient's presenting symptoms and degree of instability. Posterolateral pedicle
      screw-rod fixation has improved rates of arthrodesis compared with traditional in
      situ fusions. Nevertheless, complications with operative management of high-grade
      spondylolisthesis can be severe.

PMID- 17556126
TI  - Adolescent idiopathic scoliosis.
AB  - Conservative treatment with a brace continues to remain controversial. A recent
      study on the efficacy of brace treatment by the Scoliosis Research Society Study
      Group found it to be efficient, however, and recommends it. Surgical treatment of
      adolescent idiopathic scoliosis must be tailored to each individual need, type of
      curve, and surgeon's expertise. A straighter curve does not necessarily mean
      better for each curve. Recent advances in pedicle screw instrumentation, although
      powerful in the rate of correction achieved, carry a definitive increase in
      neurologic risk and must be used only when justified and by experienced teams.

PMID- 17556127
TI  - Operative management of degenerative scoliosis: an evidence-based approach to
      surgical strategies based on clinical and radiographic outcomes.
AB  - Degenerative scoliosis is a common and important cause of lumbar spine deformity
      in the adult. The operative management of degenerative scoliosis encompasses a
      spectrum of approaches, including decompression alone, or fusion that may include
      posterior or anterior approaches. There exists significant variability in
      surgical approaches to degenerative scoliosis, and evidence to support a specific
      approach is limited. Including the structural thoracic spine in fusions to the
      thoracolumbar junction has a lower rate of revision than fusions with a cephalad
      segment at T12 or L1. Short fusions to L5 have a low rate of revision at a
      minimum follow-up of 2 years. Combined anterior and posterior surgery is more
      effective in improving lordosis than posterior-only surgery without osteotomies.
      Clinical outcomes of surgery for degenerative scoliosis are variable, andwct 2
      self-reported scores for pain improve more reliably than scores for function.
      Further investigation, including comparison of randomized or matched cohorts and
      measurement of outcomes related to specific preoperative complaints, will be
      useful in the development of an evidence-based approach to degenerative
      scoliosis.

PMID- 17556128
TI  - Anterior instrumented arthrodesis for adult idiopathic scoliosis.
AB  - Anterior spinal arthrodesis with instrumentation is a useful alternative to
      posterior surgery in the management of thoracolumbar deformity in the adolescent
      and young adult. In adults, flexibility of primary and compensatory curves
      significantly decreases with increased age and curve magnitude. Curve flexibility
      is an important determinant of postoperative outcome. Anterior surgery is most
      appropriate for patients with moderate thoracolumbar or lumbar curves and good
      flexibility of adjacent segments. Adult patients may develop early degeneration
      at primary and compensatory curves, and these curves should be evaluated
      carefully before surgery and monitored closely during the postoperative period.
      Good results can be obtained in well-selected patients with a rigid
      instrumentation system and anterior structural grafts.

PMID- 17556129
TI  - The selection of L5 versus S1 in long fusions for adult idiopathic scoliosis.
AB  - The treatment of adult spinal deformities often involves long thoracolumbar
      fusions into the lower lumbar spine, raising the debate of selecting L5 or S1 as
      the caudal extent of the fusion. The presence of significant deformity or
      degenerative pathologic findings at L5-S1 mandates fusion to the sacrum. Fusion
      to the sacrum is of larger magnitude than fusion to L5 and introduces a higher
      surgical complication rate. Advantages of ending the fusion at L5 include
      preservation of motion, avoiding the high complication rate associated with
      fusion to the sacrum, and possibly avoiding a second operation. Complications
      with fusion to L5 include possible loss of fixation and subsequent disc
      degeneration at L5-S1, however, leading to possible pain and loss of sagittal
      balance and the need for revision surgery. To date, the functional consequences
      of an open disc space beneath long constructs remain poorly defined, and there is
      no firm evidence in the literature guiding the surgeon's choice. The issues and
      evidence guiding the decision to fuse to L5 or S1 are examined in this article.

PMID- 17556130
TI  - Flatback syndrome.
AB  - Flatback syndrome is characterized by loss of normal lumbar lordosis, resulting
      in forward tilt of the trunk, inability to stand erect, back pain, and thigh pain
      from chronic hip flexion and knee bending. The usual etiology is iatrogenic,
      through previous fusions or with extension instrumentation. Surgical treatments
      described include extension osteotomy (Smith-Petersen), pedicle subtraction
      osteotomy, and polysegmental osteotomies.

PMID- 17556131
TI  - Complex deformities of the cervical spine.
AB  - Cervical deformities arise from a multitude of causes, including genetic,
      congenital, inflammatory, degenerative, and iatrogenic etiologies. They often
      require surgical intervention for treatment of pain, progressive structural
      decompensation, and neurologic deterioration. Although congenital and hereditary
      causes of cervical deformity require specialized attention to particular clinical
      features and operative considerations, postsurgical (iatrogenic) cervical
      deformity after surgery is the most common single cause. Appropriate treatment
      involves careful selection of conservative and aggressive measures and
      familiarity with advanced surgical techniques that allow for the safe correction
      of these challenging deformities. Flexible deformities can be managed with single
      staged procedures, whereas fixed deformities require two-staged or even three
      staged procedures. Staged surgery for fixed cervical deformities can achieve up
      to 28 degrees of angular correction and 31% translational correction.

PMID- 17556132
TI  - Scheuermann's kyphosis.
AB  - Scheuermann's disease is the most common cause of structural kyphosis in
      adolescents. The kyphotic deformity is frequently attributed to "poor posture,"
      resulting in delayed diagnosis and treatment. Indications for treatment remain
      somewhat debated, because the true natural history of the disease has not been
      clearly defined. Brace treatment is almost always successful in patients with
      kyphosis between 55 degrees and 80 degrees if the diagnosis is made before
      skeletal maturity. Kyphosis greater than 80 degrees in the thoracic spine or 65
      degrees in the thoracolumbar spine is almost never treated successfully without
      surgery in symptomatic patients. Surgical treatment in adolescents and young
      adults should be considered if there is documented progression, refractory pain,
      loss of sagittal balance, or neurologic deficit. The major postoperative
      complication after surgical treatment is junctional kyphosis proximally or
      distally, which is usually related to not including all levels of the kyphosis or
      overcorrection of the deformity (>50%). With proper patient selection, excellent
      outcomes can be expected with nonoperative or operative treatment in patients
      with Scheuermann's disease.

PMID- 17556133
TI  - Other causes of pediatric deformity.
AB  - Pediatric spine deformity can result from a variety of conditions. The etiologies
      include idiopathic, congenital, neuromuscular, traumatic, iatrogenic, and
      radiation-induced spine deformities. The spine deformity may manifest as
      scoliosis, kyphosis, lordosis, or a mixed deformity. In this article, the authors
      discuss the classification, natural history, and management of congenital
      scoliosis. They conclude with a discussion of the various etiologies for
      neuromuscular scoliosis.

PMID- 17556134
TI  - Concepts of surgical correction-segmental derotation and translation techniques.
AB  - Current surgical tools and techniques allow for an unprecedented ability to
      correct even the most severe scoliotic deformities. The development of rigid
      segmental instrumentation devices (pedicle screw) has revolutionized the spine
      surgeon's capability to manipulate the spine and reduce its deformity. Rod
      rotation involves placing a preshaped rod in one or both sides of a curve and
      rotating it to achieve curve reduction. Rod translation comprises using
      specialized devices, such as a "persuader," to reduce a curve sequentially as
      vertebral segments are translated onto a rod maintained in normal position. Both
      maneuvers have become popularized to obtain triplanar correction using segmental
      instrumentation. In this article, the authors discuss and illustrate segmental
      derotation and translation techniques.

PMID- 17556135
TI  - Surgical strategies and choosing levels for spinal deformity: how high, how low,
      front and back.
AB  - The purpose of this article is to describe general strategies in the surgical
      treatment of adolescent and adult scoliosis, including radiographic evaluation,
      curve selection, principles guiding the selection of the upper and lower
      instrumented vertebrae, and indications for anterior surgery. Sagittal plane
      deformity, including Scheuermann's kyphosis, is discussed. Avoidance and
      treatment of postoperative flatback deformity is also briefly mentioned. There
      are multiple and sometimes conflicting considerations that must be reviewed when
      planning surgical stabilization of spinal deformity. Although there may be
      significant variation in surgeon decision making, careful adherence to primary
      principles, such as achieving coronal and sagittal balance in all patients and
      minimizing fusion levels, particularly in young patients, should be of paramount
      importance.

PMID- 17556136
TI  - Derotation of the spine.
AB  - Idiopathic scoliosis is a three-dimensional deformity: lateral deviation in the
      coronal plane, thoracic hypokyphosis in the sagittal plane, and rotation in the
      transverse plane affecting the ribs and trunk. With pedicle screw fixation and
      modern corrective techniques, derotation of the spine can now be accomplished.
      The goals of vertebral derotation are to achieve true three-dimensional
      correction of the spinal deformity and reverse the torsional asymmetry induced by
      scoliosis. Intuitively, in typical thoracic adolescent idiopathic scoliosis, this
      would mean optimal coronal correction, restoration of thoracic kyphosis, and
      realignment of thoracic torsion by lifting the concavity out of the chest and
      reducing the convex rib deformity without the need for thoracoplasty.

PMID- 17556137
TI  - Measuring, preserving, and restoring sagittal spinal balance.
AB  - The past decade has witnessed dramatic improvement in understanding and treatment
      of sagittal plane deformity. The authors have reviewed several studies that have
      clarified normative values for sagittal plane geometry as well as the role of the
      pelvis as we understand it today. In the treatment of lumbar degenerative disease
      with a fusion procedure, proper patient positioning and adherence to a thoughtful
      surgical plan are critical in the preservation of sagittal balance. In the event
      that restoration of sagittal alignment is required, it is best accomplished by
      the use of osteotomies, the techniques for which are described.

PMID- 17556138
TI  - Kyphectomy for myelodysplasia.
AB  - A progressive kyphotic deformity occurs in 15% of children with myelomingocele.
      The more common problems caused by the gibbus are recurrent or recalcitrant skin
      ulceration and seating difficulties. The only effective treatment is surgery.
      Excellent correction is possible by vertebrectomy of a portion of the cephalad
      limb of the deformity. Superior maintenance of the correction is accomplished by
      segmental spinal instrumentation. Alternative techniques that spare growth are
      currently being investigated. Vertebral body decancellation is one such method
      that is less extensive than vertebrectomy and, theoreticallty, allows continued
      spinal growth. It seems most appropriate for the younger patient with a less
      rigid and dramatic deformity.

PMID- 17556139
TI  - The cervicothoracic junction.
AB  - The cervicothoracic junction (CTJ) represents a unique region in the spine
      because of its biomechanical properties. It is predisposed to various traumatic
      injuries, tumor, and iatrogenic instability. It is also a difficult region to
      access anteriorly because of the vital structures ventral to the CTJ. The
      development of new surgical techniques and new instrumentation has allowed better
      access and fixation to the CTJ.

PMID- 17556140
TI  - Spinopelvic fixation in deformity: a review.
AB  - Spinopelvic fixation techniques are evolving and now seem to be converging. Good
      S1 pedicle fixation is the initial key anchor point. The tricortical technique
      tests out as the best. Supplemental fixation options are available. The most
      efficacious seems to be iliac fixation, followed by two-level structural
      interbody support. Achieving appropriate global sagittal balance also lessens the
      likelihood of implant pullout and places the fusion mass under relatively more
      compressive forces than tension forces. Regardless of the method of fixation, the
      ultimate determinant of long-term implant survival is the achievement of adequate
      biologic fusion.

PMID- 17556141
TI  - Surgical complications of spinal deformity surgery.
AB  - Spinal column reconstruction for the management of spinal deformity is
      technically challenging and has been associated with high complication rates. The
      purpose of this article is to review the major complications associated with
      spinal deformity. Major complications include pseudarthrosis, proximal junction
      kyphosis, sagittal decompensation, deep wound infection, and neurovascular
      injury. The technology and instrumentation used to treat spinal deformity
      continue to develop, and the complication rates seem to be decreasing. Although
      only trends can be identified, complications are to be expected when performing
      this surgery. Awareness of the occurrence of complications can lead to better
      information and guidance of the surgeon's expectations as well as the patient's.

PMID- 17556142
TI  - The role of osteobiologics in spinal deformity.
AB  - Spinal deformity surgery represents one of the most challenging environments in
      which to achieve bone fusion. High rates of pseudarthroses, limited quantities of
      available autograft bone, and the potential morbidity of iliac crest harvest have
      driven a search for bone graft extenders and substitutes. With expanding
      knowledge of bone biology, the authors review options in spinal fusion with a
      particular focus on deformity surgery, including the use of autograft, allograft,
      demineralized bone matrix, ceramics, and bone morphogenetic proteins.

PMID- 17556143
TI  - Measuring outcomes in spinal deformity.
AB  - The development of validated health-related quality-of-life instruments that are
      generic (Short Form-36) or disease-specific (Scoliosis Research Society [SRS]-22)
      allows physicians and researchers to measure the qualitative impact of spinal
      deformity and its treatment on their patients quantitatively. Although some
      further research may be needed in the area of the responsiveness of the SRS-22r,
      it should be considered a validated instrument that is useful in the research and
      treatment of pediatric and adult patients with spinal deformity.

PMID- 17556146
TI  - Acute variceal hemorrhage.
AB  - Variceal bleeding is a frequent and life-threatening complication of portal
      hypertension. The first episode of variceal bleeding is associated not only with
      a high mortality, but also with a high recurrence rate in those who survive.
      Therefore, management should focus on different therapeutic strategies aiming to
      prevent the first episode of variceal bleeding (primary prophylaxis), to control
      hemorrhage during the acute bleeding episode (emergency treatment), and to
      prevent rebleeding (secondary prophylaxis). These strategies involve
      pharmacological, endoscopic, surgical, and interventional radiological
      modalities. This article reviews management of acute variceal bleeding.

PMID- 17556147
TI  - Nonvariceal upper gastrointestinal bleeding.
AB  - Nonvariceal upper gastrointestinal bleeding (NVUGIB) is an important condition
      facing gastroenterologists. The focus of this article is the management of
      NVUGIB, with a particular emphasis on the endoscopic modalities and techniques
      that are most effective for various bleeding etiologies. Attention also is given
      to medical management, risk assessment, and issues pertaining to the timing of
      endoscopy and need for scheduled second-look endoscopy.

PMID- 17556148
TI  - Lower gastrointestinal bleeding.
AB  - Lower gastrointestinal (GI) hemorrhage is a significant cause of morbidity and
      mortality, particularly in elderly patients. Lower endoscopic evaluation is
      established as the diagnostic procedure of choice in the setting of acute lower
      GI hemorrhage.

PMID- 17556149
TI  - Management of ascending cholangitis.
AB  - Acute ascending cholangitis is a potential life-threatening emergency
      characterized by infection and obstruction of the biliary tree. This article
      reviews the pathogenesis and clinical approach to patients with ascending
      cholangitis and examines the literature on this topic.

PMID- 17556150
TI  - Endoscopic management of acute pancreatitis.
AB  - Acute pancreatitis represents numerous unique challenges to the practicing
      digestive disease specialist. Clinical presentations of acute pancreatitis vary
      from trivial pain to devastating acute illness with a significant risk of death.
      This article focuses on the diagnosis and endoscopic treatment of acute biliary
      pancreatitis.

PMID- 17556151
TI  - Acute colonic obstruction.
AB  - Acute colonic obstruction is a medical emergency because of the potential for
      bowel ischemia, perforation, and sepsis with peritonitis if not rapidly and
      appropriately treated. There are numerous causes of acute colonic obstruction,
      which must be differentiated from colonic pseudo-obstruction, which also is
      considered a medical emergency. Management options include medical therapy,
      surgical therapy, endoscopic therapy, and interventional radiologic therapy. Self
      expandable metal stents (SEMS) have gained acceptance for alleviating acute
      malignant colonic obstruction and in some situations for preoperative relief of
      acute benign colonic obstruction. This article reviews the approach to the
      patient who has acute colonic obstruction.

PMID- 17556152
TI  - Acute colonic pseudo-obstruction.
AB  - Acute colonic pseudo-obstruction (ACPO) is a syndrome of massive dilation of the
      colon without mechanical obstruction that develops in hospitalized patients with
      serious underlying medical and surgical conditions. Increasing age, cecal
      diameter, delay in decompression, and status of the bowel significantly influence
      mortality, which is approximately 40% when ischemia or perforation is present.
      Evaluation of the markedly distended colon involves excluding mechanical
      obstruction and other causes of toxic megacolon such as Clostridium difficile
      infection and assessing for signs of ischemia and perforation. The risk of
      colonic perforation in ACPO increases when cecal diameter exceeds 12 cm and when
      the distention has been present for greater than 6 days. Appropriate management
      includes supportive therapy and selective use of neostigmine and colonoscopy for
      decompression. Early recognition and management are critical in minimizing
      complications.

PMID- 17556153
TI  - Foreign bodies.
AB  - The spectrum of gastrointestinal (GI) foreign bodies includes food bolus
      impaction in the esophagus, nonfood objects that are swallowed, and various
      objects that may be inserted into the rectum. The risk depends upon the type of
      object and its location. Fortunately, 80% to 90% of ingested foreign bodies will
      pass without intervention. Objects with sharp edges or pointed tips have the
      highest risk of complications, up to 35%. All objects impacted in the esophagus
      require urgent or emergent treatment. Rectal foreign bodies are usually removable
      transanally, although general anesthesia and operative intervention sometimes are
      required.

PMID- 17556154
TI  - Emergency endoscopy in children.
AB  - Endoscopy in children has developed along with pediatric gastroenterology over
      the last four decades. Introduction of endoscopic techniques in adults precedes
      application in children, and pediatric endoscopists do fewer procedures than
      their adult counterparts whether routine or as an emergency. Training for
      pediatric endoscopists therefore needs to be thorough. This article in particular
      highlights developments in pediatric gastroenterology of importance to emergency
      procedures.

PMID- 17556155
TI  - Complications of endoscopy.
AB  - This article focuses on potential complications of standard upper and lower
      endoscopic procedures. Adverse events associated with endoscopic retrograde
      cholangiopancreatography, EUS, and certain advanced therapeutic techniques such
      as mucosal resection are not covered. Rather, the article focuses on the
      recognition of preprocedure risk factors for various complications and the
      diagnosis and management for procedure-related adverse events.

PMID- 17556156
TI  - CT angiography: too much too soon?

PMID- 17556157
TI  - Mental stress-induced myocardial ischemia: moving forward.

PMID- 17556158
TI  - The importance of the link between coronary artery calcification and myocardial
      ischemia: a developing argument.

PMID- 17556159
TI  - Image-guided cardiovascular functional genomics: finding the needle in the
      haystack.

PMID- 17556160
TI  - Fifth Annual Mario S. Verani, MD Memorial Lecture: evolving challenges and
      opportunities.

PMID- 17556161
TI  - Risk stratification after acute myocardial infarction: is it time to reassess?
      Implications from the INSPIRE trial.

PMID- 17556162
TI  - Atheroma roulette.

PMID- 17556163
TI  - Evaluation of left ventricular mechanical dyssynchrony as determined by phase
      analysis of ECG-gated SPECT myocardial perfusion imaging in patients with left
      ventricular dysfunction and conduction disturbances.
AB  - BACKGROUND: Cardiac resynchronization therapy (CRT) is approved for the treatment
      of patients with advanced systolic heart failure and evidence of dyssynchrony on
      electrocardiograms. However, a significant percentage of patients do not
      demonstrate improvement with CRT. Echocardiographic techniques have been used for
      more accurate determination of dyssynchrony. Single photon emission computed
      tomography (SPECT) myocardial perfusion imaging has not previously been used to
      evaluate cardiac dyssynchrony. The objective of this study is to evaluate
      mechanical dyssynchrony as described by phase analysis of gated SPECT images in
      patients with left ventricular dysfunction, conduction delays, and ventricular
      paced rhythms. METHODS AND RESULTS: A novel count-based method is used to extract
      regional systolic wall thickening amplitude and phase from gated SPECT images.
      Five indices describing the phase dispersion of the onset of mechanical
      contraction are determined: peak phase, phase SD, bandwidth, skewness, and
      kurtosis. These indices were determined in consecutive patients with left
      ventricular dysfunction (n = 120), left bundle branch block (n = 33), right
      bundle branch block (n = 19), and ventricular paced rhythms (n = 23) and were
      compared with normal control subjects (n = 157). Phase SD, bandwidth, skewness,
      and kurtosis were significantly different between patients with left ventricular
      dysfunction, left bundle branch block, right bundle branch block, and ventricular
      paced rhythms and normal control subjects (all P < .001) Peak phase was
      significantly different between patients with right ventricular paced rhythms and
      normal control subjects (P = .001). CONCLUSIONS: A novel SPECT technique for
      describing left ventricular mechanical dyssynchrony has been developed and may
      prove useful in the evaluation of patients for CRT.

PMID- 17556164
TI  - Mental stress-induced myocardial ischemia in coronary artery disease patients
      with left ventricular dysfunction.
AB  - BACKGROUND: Reduced left ventricular ejection fraction (LVEF) is a risk factor
      for poor outcomes in patients with coronary artery disease (CAD). Mental stress
      induced myocardial ischemia (MSIMI) also identifies a subset of CAD patients at
      increased risk for future cardiovascular events. Susceptibility to MSIMI in
      patients with CAD and reduced LVEF is unknown. METHODS AND RESULTS: We enrolled
      182 patients (67 women) with a mean age of 64 years and a documented history of
      CAD in this study. Baseline resting ejection fraction was determined by use of
      technetium 99m sestamibi gated single photon emission computed tomography.
      Abnormal LVEF was defined as less than 45% for men and less than 50% for women
      (based on published norms for our software [Cedars-Sinai Medical Center]). All
      participants underwent mental stress testing with a public speaking task.
      Rest/stress myocardial perfusion single photon emission computed tomography was
      performed via conventional methodology. Images were visually compared for number
      and severity of perfusion defects by use of a scoring method from 0 to 4. A
      summed difference score was calculated as the difference between summed stress
      and rest scores. A score of greater than 3 was considered abnormal. MSIMI
      developed in 19% of patients with normal LVEF and 31% of those with reduced LVEF.
      There is no statistically significant difference between the two groups (P =
      .11). CONCLUSIONS: CAD patients with left ventricular dysfunction are equally
      susceptible to MSIMI as those with normal LVEF.

PMID- 17556165
TI  - CT-based attenuation correction versus prone imaging to decrease equivocal
      interpretations of rest/stress Tc-99m tetrofosmin SPECT MPI.
AB  - BACKGROUND: The purpose of this study was to compare stress supine single photon
      emission computed tomography (SPECT) imaging with attenuation correction (AC) via
      computed tomography-based attenuation maps with stress prone SPECT imaging with
      regard to the rate of equivocal interpretation of rest/stress myocardial
      perfusion imaging. METHODS AND RESULTS: Interpretations for 324 consecutive
      patients referred for rest/stress myocardial perfusion imaging were performed by
      use of the following sets of poststress SPECT images: supine with no AC (NC),
      supine NC/AC, supine NC/prone, and all images. The number of equivocal studies
      decreased with additional imaging: supine NC, 40%; supine NC/prone, 18%; supine
      NC/AC, 11%; and all images, 8%. The supine NC/AC sets of images reduced the
      number of defects to a greater extent than the supine NC/prone images for all
      patients (P = .01), men (P = .002), and women (P = .425). For the inferior (but
      not the anterior) wall, the percent decrease in defects with supine NC/AC images
      was lower as compared with supine NC/prone images. CONCLUSION: Interpretation
      with all images resulted in the fewest equivocal studies. The supine NC/AC images
      reduced the number of equivocal studies to a greater extent than the supine
      NC/prone images. AC and prone imaging were more helpful in men than women and
      were more helpful to resolve inferior than anterior wall defects. Adding prone
      imaging to supine imaging without and with AC does not significantly alter the
      number of equivocal interpretations.

PMID- 17556166
TI  - A Bayesian iterative transmission gradient reconstruction algorithm for cardiac
      SPECT attenuation correction.
AB  - BACKGROUND: High-quality attenuation maps are critical for attenuation correction
      of myocardial perfusion single photon emission computed tomography studies. The
      filtered backprojection (FBP) approach can introduce errors, especially with low
      count transmission data. We present a new method for attenuation map
      reconstruction and examine its performance in phantom and patient data. METHODS
      AND RESULTS: The Bayesian iterative transmission gradient algorithm incorporates
      a spatially varying gamma prior function that preferentially weights estimated
      attenuation coefficients toward the soft-tissue value while allowing data-driven
      solutions for lung and bone regions. The performance with attenuation-corrected
      technetium 99m sestamibi clinical images was evaluated in phantom studies and in
      50 low-likelihood patients grouped by body mass index (BMI). The algorithm
      converged in 15 iterations in the phantom studies. For the clinical studies, soft
      tissue estimates had significantly greater uniformity of mediastinal coefficients
      (mean SD, 0.005 cm(-1) vs 0.011 cm(-1); P < .0001). The accuracy and uniformity
      of the Bayesian iterative transmission gradient algorithm were independent of
      BMI, whereas both declined at higher BMI values with FBP. Attenuation-corrected
      perfusion images showed improvement in myocardial wall variability (4.8% to 4.1%,
      P = .02) for all BMI groups with the new method compared with FBP. CONCLUSION:
      This new method for attenuation map reconstruction provides rapidly converging
      and accurate attenuation maps over a wide spectrum of patient BMI values and
      significantly improves attenuation-corrected perfusion images.

PMID- 17556168
TI  - Severe coronary artery calcifications are associated with ischemia in patients
      undergoing medical therapy.
AB  - BACKGROUND: The role of coronary artery calcification (CAC) detection in
      individuals undergoing medical therapy is controversial. These patients
      frequently exhibit an artificially low clinical suspicion for obstructive heart
      disease. Whether detection of CAC adds value to their assessment is unknown.
      METHODS AND RESULTS: We conducted a cross-sectional analysis of 703 adequately
      treated individuals who had CAC scoring with electron beam computed tomography
      and myocardial perfusion imaging within 6 months. We assessed the association of
      risk factor analysis and CAC scoring with myocardial perfusion imaging
      abnormalities. Univariate associations between ischemia and male gender, low high
      density lipoprotein, high body mass index, diabetes, and CAC score were noted.
      Despite reasonable control of blood pressure and low-density lipoprotein, the
      prevalence of inducible ischemia was 0.8%, 4.8%, 5.7%, 8.0%, and 15.1% across CAC
      scores of 0 to 10, 11 to 100, 101 to 400, 401 to 1000, and greater than 1000,
      respectively (P < .001 for trend). Logistic regression analysis demonstrated
      that, after adjustment for risk factors, the odds of ischemia was 3.0 (95%
      confidence interval, 1.5-5.7) in individuals with CAC scores greater than 400
      compared with those with CAC scores of 400 or less. CONCLUSIONS: The presence of
      a CAC score greater than 400 is associated with ischemia in a population
      receiving good medical therapy. The detection of significant CAC in these
      individuals warrants additional evaluation for ischemia.

PMID- 17556167
TI  - Influence of the postexercise acquisition delay on the detection of functional
      abnormalities in sestamibi-gated SPECT.
AB  - BACKGROUND: Gated single photon emission computed tomography (SPECT) identifies
      functional changes produced by ischemia, but the influence of acquisition delay
      on their detection is not established. METHODS AND RESULTS: In 80 patients with
      known or suspected coronary artery disease, gated SPECT was acquired twice:
      first, less than 30 minutes after peak exercise (stress 1), and second, more than
      45 minutes after peak exercise (stress 2). End-diastolic volume (EDV), end
      systolic volume (ESV), and ejection fraction (EF) were compared with perfusion.
      The relationship between the DeltaEF (stress EF - resting EF) and the summed
      difference score (SDS) was -0.443 (P < .0001) for stress 1 and -0.416 (P < .0001)
      for stress 2. In stress 1, EF increased in patients without inducible ischemia
      (SDS = 0) (57% +/- 10% vs 54% +/- 9% at rest, P < .02) and decreased in those
      with an SDS of 1 or greater (53% +/- 10.8% vs 55% +/- 9.6% at rest, P < .05). In
      stress 2, EF was unchanged in patients without ischemia (55.8% +/- 9.7%, P = .06)
      and decreased in the other patients (52.8% +/- 10.2%, P < .01). In patients
      without ischemia, both the EDV and ESV decreased significantly in stress 1 and
      were unchanged in stress 2. In patients with an SDS of 1 or greater, the EDV
      remained unchanged and the ESV minimally decreased in stress 1, whereas both
      volumes clearly and significantly increased in stress 2. CONCLUSIONS: The early
      acquisition of postexercise gated SPECT is slightly more effective in detecting
      ischemia-related functional changes; however, a delayed acquisition within 60
      minutes still permits the detection of functional abnormalities in most patients.

PMID- 17556169
TI  - Fragmented QRS complexes not typical of a bundle branch block: a marker of
      greater myocardial perfusion tomography abnormalities in coronary artery disease.
AB  - BACKGROUND: Fragmented QRS (FQRS) complexes, not typical of a bundle branch
      block, are a marker of regional myocardial injury. The extent of stress
      myocardial perfusion imaging (MPI) abnormalities with FQRS patterns is not known.
      METHODS AND RESULTS: Twelve-lead electrocardiograms (ECGs) in 501 patients
      undergoing stress MPI were studied. FQRS was defined as a QRS duration of 120
      milliseconds or less, with notches or slurs of QRS complexes, on 2 contiguous
      leads of a coronary artery territory. Abnormal MPI was defined as a regional
      summed stress score (SSS) and summed rest score (SRS) of 3 or greater based on a
      17-segment model. Patients with a typical bundle (n = 26), paced rhythm (n = 2),
      and Q waves (n = 64) were excluded. Of the remaining 409 patients (mean age, 58
      +/- 13 years; 52% male), 155 (38%) had FQRS on the ECG. FQRS patients had a
      higher mean SSS, SRS, and global summed difference score and a lower left
      ventricular ejection fraction (all P < .001), as well as greater regional stress
      MPI scar (69% vs 11%, P < .001). FQRS pattern sensitivity was 75% and specificity
      was 94% for a corresponding regional MPI scar. On logistic regression, SSS, SRS,
      summed difference score, left ventricular ejection fraction, and regional scar
      were univariate predictors of the FQRS pattern on the ECG (all P < .01), and any
      regional scar (odds ratio, 32; P < .001) was a multivariate predictor.
      CONCLUSIONS: FQRS complexes on an ECG are a marker of higher stress MPI perfusion
      and functional abnormalities. Regional FQRS patterns denote the presence of a
      greater corresponding focal regional myocardial scar on stress MPI.

PMID- 17556171
TI  - What does the clinical cardiologist need from noninvasive cardiac imaging: is it
      time to adjust practices to meet evolving demands?
AB  - With the recent emergence of multidetector computed tomography angiography,
      coronary anatomy can now be assessed noninvasively. Until this advancement,
      functional noninvasive imaging used to serve as a gatekeeper that governed access
      to invasive diagnosis by coronary angiography and subsequent therapy. In the
      current era the threshold for access to coronary anatomy will be lowered.
      Functional noninvasive imaging will often come second, while anatomy is known
      already. If appropriate use of revascularization procedures is to be promoted,
      functional evaluation shall play an even greater role than before as a guide for
      selection of therapy. In subjects screened while the atherosclerotic disease is
      still at a preclinical stage, the ability to image plaque activity in the absence
      of flow-limiting stenosis will be essential in our attempts to prevent sudden
      ischemic cardiac death and unheralded myocardial infarction. In patients with
      advanced age and extensive obstructive disease, the diagnostic performance of
      functional testing will have to be raised by shifting from "per-patient" to "per
      vessel" accuracy. Reengineering of currently available methods or the development
      of novel technologies that provide an integrative evaluation of anatomy and
      function will be necessary. With the availability of an increasing number of
      imaging options, it is anticipated that the emphasis will be placed more than
      ever on cost-effectiveness on a population basis, as well as on segmental
      predictive accuracy in the individual subject.

PMID- 17556170
TI  - Myocardial perfusion, oxidative metabolism, and free fatty acid uptake in
      patients with hypertrophic cardiomyopathy attributable to the Asp175Asn mutation
      in the alpha-tropomyosin gene: a positron emission tomography study.
AB  - BACKGROUND: The relationship between myocardial metabolic changes and the
      severity of left ventricular (LV) hypertrophy in patients with hypertrophic
      cardiomyopathy (HCM) is largely unknown. We characterized metabolic abnormalities
      in patients with a genetically identical cause for HCM but with variable LV
      hypertrophy. METHODS AND RESULTS: Eight patients with HCM attributable to the
      Asp175Asn mutation in the alpha-tropomyosin gene underwent myocardial perfusion,
      oxidative, and free fatty acid (FFA) metabolism measurements via positron
      emission tomography and oxygen 15-labeled water, carbon 11 acetate, and fluorine
      14(R,S)-[18F] Fluoro-6-thia-heptadecanoic acid (18 FTHA). LV mass, work, and
      efficiency were assessed by echocardiography. Thirty-six healthy volunteers
      served as control subjects. Compared with control subjects, HCM patients had
      increased myocardial oxidative metabolism and FFA uptake (P < .05). However, in
      patients, LV mass was inversely related to global myocardial perfusion, oxidative
      metabolism, and FFA uptake (all P < .03), and regional wall thickness was
      inversely related to regional perfusion (P < .01), oxidative metabolism (P <
      .001), and FFA uptake (P < .01). Therefore patients with mild (LV mass less than
      median of 177 g) but not advanced LV hypertrophy were characterized by increased
      perfusion, oxidative metabolism, and LV efficiency as compared with control
      subjects (P < .05). CONCLUSIONS: In HCM attributable to the Asp175Asn mutation in
      the alpha-tropomyosin gene, myocardial oxidative metabolism and FFA metabolism
      are increased and inversely related to LV hypertrophy at both the whole heart and
      regional level. Increased metabolism and efficiency characterize patients with
      mild myocardial hypertrophy. These hypermetabolic alterations regress with
      advanced hypertrophy.

PMID- 17556172
TI  - Monitoring left ventricular function in small animals.
AB  - Small animals such as mice and rats are extensively used to investigate the
      mechanisms and treatment of human cardiac diseases in vivo. The monitoring of
      left ventricular function is a key factor in this research. The measurement
      should be rapid, reproducible, and repeatable and allow the detection of subtle
      differences in function. Currently, echocardiography is most widely used in
      cardiac research laboratories for measuring left ventricular dimensions and
      function in small animals. Although the technique is rapid, the reproducibility
      of the calculations of left ventricular volumes is limited in some circumstances
      as a result of assumptions that do not necessarily hold true, such as in the
      setting of dilated, failing ventricles.

PMID- 17556174
TI  - Left ventricular hypertrophy and SPECT myocardial perfusion imaging: finding the
      diamonds in the rough.

PMID- 17556173
TI  - Will 3-dimensional PET-CT enable the routine quantification of myocardial blood
      flow?
AB  - Quantification of myocardial blood flow (MBF) and flow reserve has been used
      extensively with positron emission tomography (PET) to investigate the functional
      significance of coronary artery disease. Increasingly, flow quantification is
      being applied to investigations of microvascular dysfunction in early
      atherosclerosis and in nonatherosclerotic microvascular disease associated with
      primary and secondary cardiomyopathies. Fully three-dimensional (3D) acquisition
      is becoming the standard imaging mode on new equipment, bringing with it certain
      challenges for cardiac PET, but also the potential for MBF to be measured
      simultaneously with routine electrocardiography (ECG)-gated perfusion imaging.
      Existing 3D versus 2D comparative studies support the use of 3D cardiac PET for
      flow quantification, and these protocols can be translated to PET-CT, which
      offers a virtually noise-free attenuation correction. This technology combines
      the strengths of cardiac CT for evaluation of anatomy with cardiac PET for
      quantification of the hemodynamic impact on the myocardium. High throughput
      clinical imaging protocols are needed to evaluate the incremental diagnostic and
      prognostic value of this technology.

PMID- 17556175
TI  - Images of Prinzmetal's angina: a case report.

PMID- 17556176
TI  - Adenosine stress protocols for myocardial perfusion imaging.

PMID- 17556177
TI  - Synthesis and validation of fatty acid analogs radiolabeled by nonisotopic
      substitution.

PMID- 17556178
TI  - The role and regulation of CD36 for fatty acid imaging of the heart: implications
      in diabetes mellitus and chronic kidney disease.

PMID- 17556179
TI  - Imaging of myocardial fatty acid metabolism with PET.

PMID- 17556180
TI  - Myocardial perfusion imaging in the acute care setting.

PMID- 17556181
TI  - Myocardial perfusion imaging in the evaluation of chest pain in the acute care
      setting: Clinical and economic outcomes.

PMID- 17556182
TI  - Myocardial metabolic imaging in the acute care setting.

PMID- 17556183
TI  - The Japanese experience with metabolic imaging in the clinical setting.

PMID- 17556184
TI  - Future directions of myocardial fatty acid imaging.

PMID- 17556185
TI  - Metabolic adaptation to myocardial ischemia: the role of fatty acid imaging.

PMID- 17556186
TI  - Acute and chronic management in patients with Brugada syndrome associated with
      electrical storm of ventricular fibrillation.
AB  - BACKGROUND: Some patients with Brugada syndrome experience an electrical storm of
      ventricular fibrillation (VF). OBJECTIVE: The purpose of this study was to
      investigate the clinical, laboratory, electrocardiographic, and
      electrophysiologic characteristics, acute and subsequent chronic treatment, and
      follow-up data of patients with Brugada syndrome associated with electrical storm
      of VF. METHODS: Sixty-seven patients with Brugada syndrome (65 men and 2 women,
      age 46 +/- 14 years) were divided into three groups: 7 patients with a history of
      electrical storm of VF (group I), 39 symptomatic patients with documented VF
      and/or syncope (group II), and 21 asymptomatic patients (group III). Electrical
      storm was defined as three or more episodes of VF per day recorded by the memory
      of an implantable cardioverter-defibrillator. RESULTS: No significant differences
      were observed among the three groups with regard to clinical (age at diagnosis,
      familial history of sudden cardiac death), laboratory (SCN5A mutation and serum
      potassium level), electrocardiographic and electrophysiologic characteristics,
      and follow-up duration after diagnosis. However, arrhythmic events during follow
      up after diagnosis and number of arrhythmic events per patient were significantly
      higher in group I compared with groups II and III. Isoproterenol infusion (0.003
      +/- 0.003 microg/kg/min for 24 +/- 13 days) completely suppressed electrical
      storm of VF in all five patients treated and was successfully replaced with oral
      medications, including denopamine, quinidine, isoproterenol, cilostazol, and
      bepridil alone or in combination. CONCLUSION: No specifically clinical,
      laboratory, electrocardiographic, and electrophysiologic characteristics were
      recognized in patients with Brugada syndrome associated with electrical storm of
      VF. Isoproterenol infusion was effective as an acute treatment in suppressing
      electrical storm of VF and was successfully replaced with chronic oral
      medications.

PMID- 17556187
TI  - Treatment of ventricular fibrillation storm in Brugada syndrome: weathering the
      storm but staying in hot water?

PMID- 17556188
TI  - Participation of a concealed atriohisian tract in the reentrant circuit of the
      slow-fast type of atrioventricular nodal reentrant tachycardia.
AB  - BACKGROUND: The retrograde fast pathway in typical atrioventricular nodal
      reentrant tachycardia (AVNRT) exhibits marked variation in its electrophysiologic
      properties. OBJECTIVE: The purpose of this study was to characterize the
      retrograde fast pathway and localize the lower turnaround site of the reentrant
      circuit in typical AVNRT. METHODS: Seventy-four patients with typical AVNRT were
      divided into two groups according to the response of the retrograde fast pathway
      to intravenous administration of adenosine triphosphate (ATP) during ventricular
      pacing: ATP-S [n = 47 (63.5%)] with and ATP-R without [n = 27 (36.5%)] His-atrial
      (H-A) block. H-A intervals were measured from the most proximal His-bundle
      electrogram to the earliest atrial activation during the tachycardia (HAt) and
      entrainment pacing from the parahisian right ventricular region (HAe). It was
      postulated that the HAt was the difference in conduction time between the lower
      common pathway (x) and retrograde fast pathway (y) (HAt = y - x), whereas HAe was
      the sum of the two (HAe = y + x). Hence, x = (HAe-HAt)/2. x >0 suggested the
      presence of a lower common pathway, whereas x <0 suggested the absence of a lower
      common pathway and lower turnaround site within the His bundle. RESULTS: x was
      significantly smaller in ATP-R than ATP-S (-6 +/- 5 vs 4 +/- 4 ms, P <.05) and
      was <0 in 23 (85%) of 27 ATP-R patients. The maximal increment in H-A interval
      during ventricular pacing was significantly longer in ATP-S than ATP-R (35 +/- 33
      vs 2 +/- 2 ms, P <.05). CONCLUSION: A concealed atriohisian tract totally
      bypassing the atrioventricular node constituted the retrograde fast pathway in
      one third of all typical AVNRT cases.

PMID- 17556189
TI  - Common form of atrioventricular nodal reentrant tachycardia: do we really know
      the circuit we try to ablate?

PMID- 17556190
TI  - Electrophysiologic delineation of the tachycardia circuit in the slow-slow form
      of atrioventricular nodal reentrant tachycardia.
AB  - BACKGROUND: Little is known about the exact boundaries of the reentrant circuit
      in the slow-slow form of atrioventricular nodal reentrant tachycardia (AVNRT).
      OBJECTIVE: The purpose of this study was to examine the tachycardia circuit in
      the slow-slow form of AVNRT. METHODS: Single extrastimuli were delivered during
      the slow-slow form of AVNRT at 10 sites along the right interatrial septum:
      superior portion of the His-bundle (HB) site, the HB site, three equidistantly
      divided sites of the AV junction between HB site and coronary sinus ostium (CSOS;
      sites S, M, and I), and inferior, superior, posterior, posteroinferior, and
      internal portions of the CSOS in 13 patients. The longest coupling interval of a
      single extrastimulus that reset the tachycardia and the following return cycle
      were measured. RESULTS: The tachycardia cycle length was 409 +/- 50 ms. The
      earliest atrial electrogram during tachycardia was observed at site I in all
      patients. The longest coupling intervals at superior-HB, HB site, sites S, M, and
      I, and inferior-CSOS, superior-CSOS, posterior-CSOS, posteroinferior-CSOS, and
      internal-CSOS were 340 +/- 52, 355 +/- 50, 367 +/- 50, 378 +/- 51, 398 +/- 49,
      398 +/- 52, 355 +/- 60, 351 +/- 50, 371 +/- 48, and 363 +/- 54 ms, respectively.
      The following return cycles were 468 +/- 52, 453 +/- 52, 442 +/- 52, 431 +/- 50,
      411 +/- 52, 410 +/- 49, 454 +/- 45, 457 +/- 57, 438 +/- 54, and 445 +/- 53 ms,
      respectively. The longest coupling intervals at site I and inferior-CSOS were
      significantly longer than those at the other sites (P <.0001). The return cycles
      at site I and inferior-CSOS did not differ from the tachycardia cycle length,
      whereas those at the other sites were significantly longer than the tachycardia
      cycle length (P <.0001). CONCLUSION: Site I and inferior-CSOS are involved in the
      slow-slow form of AVNRT circuit, and the atrial tissue between those sites form
      an integral limb of the reentrant circuit.

PMID- 17556191
TI  - Electrical isolation of the posterior left atrial wall and pulmonary veins for
      atrial fibrillation: feasibility of and rationale for a single-ring approach.
AB  - BACKGROUND: Wide electrical pulmonary vein isolation (PVI) with two separate
      rings of ablation requires extensive ablation on the posterior left atrial wall
      close to the esophagus. OBJECTIVE: The purpose of this study was to determine the
      feasibility of PVI using a single ring of radiofrequency ablation lesions.
      METHODS: Irrigated-tip ablation catheters, deflectable sheaths, and computerized
      tomographic image integration were used to isolate the pulmonary veins and
      posterior wall of the left atrium in 41 patients with a single ring of
      radiofrequency ablation lesions. The procedural details were compared with a
      consecutive series of 41 historical controls who underwent PVI with two separate
      rings around the ipsilateral vein pairs. RESULTS: Isolation with a single ring
      was possible in 39 of 41 cases. Ablation was required within the ring at the
      venous side of the ridge separating the left atrial appendage and left pulmonary
      veins (n = 17, 43%) or within the roofline (n = 16, 40%). The length of linear
      lesions adjacent to the esophagus was shorter in the single-ring group (19 +/- 10
      mm vs. 31 +/- 14 mm; P = .01). The procedural times, number of ablation sites,
      duration of ablation required to achieve PVI, and rhythm outcomes at 6 months
      were similar in the two groups. CONCLUSIONS: Radiofrequency ablation using an
      open irrigated-tip ablation catheter can be used to reliably electrically isolate
      the pulmonary veins with a single large circular lesion. PVI can be achieved with
      a similar procedural and ablation time. The major problem areas were identified
      as the roof of the left atrium and the ridge separating the left-sided veins from
      the left atrial appendage.

PMID- 17556192
TI  - Can we compartmentalize the left atrium in the electrophysiology laboratory?

PMID- 17556193
TI  - A mechanism for sudden infant death syndrome (SIDS): stress-induced leak via
      ryanodine receptors.
AB  - BACKGROUND: Sudden infant death syndrome (SIDS) is the leading cause of
      postneonatal mortality in the United States. Mutations in the RyR2-encoded
      cardiac ryanodine receptor cause the highly lethal catecholaminergic polymorphic
      ventricular tachycardia (CPVT1) in the young. OBJECTIVE: The purpose of this
      study was to determine the spectrum and prevalence of RyR2 mutations in a large
      cohort of SIDS cases. METHODS: Using polymerase chain reaction, denaturing high
      performance liquid chromatography, and direct DNA sequencing, a targeted
      mutational analysis of RyR2 was performed on genomic DNA isolated from frozen
      necropsy tissue on 134 unrelated cases of SIDS (57 females, 77 males; 83 white,
      50 black, 1 Hispanic; average age = 2.7 months). RyR2 mutations were engineered
      by site-directed mutagenesis, heterologously expressed in HEK293 cells, and
      functionally characterized using single-channel recordings in planar lipid
      bilayers. RESULTS: Overall, two distinct and novel RyR2 mutations were identified
      in two cases of SIDS. A 6-month-old black female hosted an R2267H missense
      mutation, and a 4-week-old white female infant harbored a S4565R mutation. Both
      nonconservative amino acid substitutions were absent in 400 reference alleles,
      involved conserved residues, and were localized to key functionally significant
      domains. Under conditions that simulate stress [Protein Kinase A (PKA)
      phosphorylation] during diastole (low activating [Ca2+]), SIDS-associated RyR2
      mutant channels displayed a significant gain-of-function phenotype consistent
      with the functional effect of previously characterized CPVT-associated RyR2
      mutations. CONCLUSIONS: Here we report a novel pathogenic mechanism for SIDS,
      whereby SIDS-linked RyR2 mutations alter the response of the channels to
      sympathetic nervous system stimulation such that during stress the channels
      become "leaky" and thus potentially trigger fatal cardiac arrhythmias.

PMID- 17556194
TI  - Cardiac arrhythmias of genetic origin are important contributors to sudden infant
      death syndrome.

PMID- 17556196
TI  - When will we know enough to treat atrial fibrillation?

PMID- 17556195
TI  - Polymorphism modulates symptomatic response to antiarrhythmic drug therapy in
      patients with lone atrial fibrillation.
AB  - BACKGROUND: The angiotensin-converting enzyme (ACE) deletion allele, ACE D, is
      associated with increased ACE activity and adverse outcomes in cardiovascular
      disease. Although activation of the renin-angiotensin-aldosterone system (RAAS)
      now appears to play a role in the pathophysiology of atrial fibrillation (AF), it
      remains to be determined if ACE genotype impacts response to conventional AAD
      therapy in patients with AF. OBJECTIVES: The purpose of this study was to
      investigate whether response to antiarrhythmic drug (AAD) therapy in patients
      with AF is modulated by the ACE I/D polymorphism. METHODS: We studied 213
      patients (147 men, 66 women; ages 52 +/- 15 years) prospectively enrolled in the
      Vanderbilt AF Registry. AAD therapy outcome was defined prospectively as response
      if there was a >or=75% reduction in symptomatic AF burden or nonresponse if AF
      burden was unchanged, necessitating a change in drugs or therapy. RESULTS: Lone
      AF (age <65 years, no identifiable cause) was present in 72 (34%) patients,
      whereas hypertension was the most common underlying disease in the remaining 141
      (41%). AF was paroxysmal in 170 (80%) and persistent in 43 (20%). The frequencies
      of the DD, ID, and II genotypes were in Hardy-Weinberg equilibrium. Lone AF and
      DD/ID genotypes were highly significant predictors of failure of drug therapy (P
      <.005). In patients with lone AF, failure of drug response was 5%, 41%, and 47%
      in patients with II, ID, and DD genotypes, respectively, (P <.005, II vs. ID/DD).
      CONCLUSIONS: These results provide further evidence for a role of RAAS activation
      in the pathophysiology of AF and point to a potential role for stratification of
      therapeutic approaches by ACE genotype.

PMID- 17556197
TI  - Exclusion of multiple candidate genes and large genomic rearrangements in SCN5A
      in a Dutch Brugada syndrome cohort.
AB  - BACKGROUND: The Brugada syndrome is an inherited cardiac electrical disorder
      associated with a high incidence of life-threatening arrhythmias. Screening for
      mutations in the cardiac Na+ channel-encoding gene SCN5A uncovers a mutation in
      approximately 20% of Brugada syndrome cases. Genetic heterogeneity and/or
      undetected SCN5A mutations, such as exon duplications and deletions, could be
      involved in the remaining 80% mutation-negative patients. OBJECTIVES: Thirty
      eight SCN5A mutation-negative Dutch Brugada syndrome probands were studied. The
      SCN5A gene was investigated for exon duplication and deletion, and a number of
      candidate genes (Caveolin-3, Irx-3, Irx-4, Irx-5, Irx-6, Plakoglobin, Plakophilin
      2, SCN1B, SCN2B, SCN3B, and SCN4B) were tested for the occurrence of point
      mutations and small insertions/deletions. METHODS: We used a quantitative
      multiplex approach to determine SCN5A exon copy numbers. Mutation analysis of the
      candidate genes was performed by direct sequencing of polymerase chain reaction
      amplified coding regions. RESULTS: No large genomic rearrangements in SCN5A were
      identified. No mutations were found in the candidate genes. Twenty novel
      polymorphisms were identified in these genes. CONCLUSION: Large genomic
      rearrangements in SCN5A are not a common cause of Brugada syndrome. Similarly,
      the studied candidate genes are unlikely to be major causal genes of Brugada
      syndrome. Further studies are required to identify other genes responsible for
      this syndrome.

PMID- 17556198
TI  - Genetic basis of Brugada syndrome.

PMID- 17556199
TI  - Transmural and endocardial Purkinje activation in pigs before local myocardial
      activation after defibrillation shocks.
AB  - BACKGROUND: Earliest recorded postshock myocardial activations in pigs originate
      in the subepicardium of the apex and lateral free wall of the left ventricle (LV)
      30-90 ms after the shock. OBJECTIVE: The purpose of this study was to determine
      whether the Purkinje system is a candidate for the source of postshock
      activations by performing endocardial and transmural postshock activation
      mapping. METHODS: In five pigs, 32 plunge needles with 12 electrodes (1-mm
      spacing) were inserted into the LV apex and lateral free wall. Up to 70 plunge
      needles with six electrodes (2-mm spacing) were spread throughout the remainder
      of the LV, while 9-12 plunge needles with four electrodes (2-mm spacing) were
      inserted into the right ventricle. A basket catheter with 32 bipolar recording
      sites was inserted into the LV. Defibrillation-threshold (DFT)-level shocks were
      delivered during 10 episodes of electrically induced ventricular fibrillation.
      Electrograms of postshock activation cycles were analyzed for Purkinje and
      myocardial activations. RESULTS: Purkinje activations were recorded before local
      myocardial activation in 9% of basket electrograms and in 15% of plunge needles
      during the first postshock activation cycle. Purkinje activations were identified
      during the first and subsequent several postshock activation cycles in at least
      one basket and one needle electrogram in 96% and 98% of defibrillation episodes,
      respectively. CONCLUSIONS: The Purkinje system is active during the early
      postshock activation cycles after DFT-level shocks. Further studies are required
      to determine whether activation initiates in the Purkinje system or whether it is
      activated by the myocardium or by Purkinje-myocardial junctional cells.

PMID- 17556200
TI  - Drawing the curtain on the isoelectric window?

PMID- 17556201
TI  - Arrhythmogenic consequences of Na+ channel mutations in the transmurally
      heterogeneous mammalian left ventricle: analysis of the I1768V SCN5A mutation.
AB  - BACKGROUND: Congenital mutations in the cardiac Na+ channel (encoded by SCN5A)
      underlie long QT syndrome type 3. The sea anemone peptide toxin ATX-II mimics the
      slowed inactivation kinetics characteristic of many long QT type 3 (LQT3)
      mutations. However, the I1768V SCN5A mutation is associated with faster recovery
      kinetics, for which there exists no known pharmacologic equivalent. OBJECTIVE:
      The purpose of this study was to investigate the proarrhythmic consequences of
      the I1768V SCN5A mutation in a transmurally heterogeneous canine left ventricular
      wedge. We hypothesized that amplification of intrinsic electrical heterogeneities
      may contribute to abnormal repolarization patterns. METHODS: We developed a
      multiscale computational model of the canine ventricular wedge preparation that
      accounts for a comprehensive set of ionic currents (including transmural
      heterogeneities of the voltage-dependent transient outward current I(Kv43), the
      late sodium current I(NaL), the slowly activating delayed rectifier current
      I(Ks), and the sarco[endo]plasmic reticulum Ca2+-ATPase pump SERCA) and includes
      mechanistic descriptions of intracellular Ca2+ cycling, the effects of ATX-II,
      and the I1768V mutation. RESULTS: Experimentally observed QT intervals and rate
      dependent transmural gradients in action potential duration were recapitulated in
      our simulations, both with and without ATX-II. With the I1768V SCN5A mutation,
      the model predicted endocardial early afterdepolarizations that triggered
      epicardial beats and R-on-T extrasystoles. Brief episodes of polymorphic,
      followed by sustained monomorphic, ventricular tachycardia were observed at slow
      pacing rates. Importantly, these arrhythmias are driven by recurring reactivation
      of Na+ channels localized to the endocardium. CONCLUSION: Our findings suggest
      that an increase in sustained inward Na+ current arising from the I1768V SCN5A
      mutation leads to clinically relevant arrhythmias in the transmurally
      heterogeneous canine left ventricular myocardium. This novel approach for
      simulating transmural heterogeneity provides new insight into the development of
      rhythm disturbances in the mammalian left ventricle.

PMID- 17556202
TI  - The heart on a chip: the role of realistic mathematical models of cardiac
      electrical activity in understanding and treating cardiac arrhythmias.

PMID- 17556203
TI  - Pacemaker interference with an iPod.

PMID- 17556204
TI  - Failure of an implantable cardioverter-defibrillator to detect sustained
      ventricular tachycardia: a consequence of the latching phenomenon.

PMID- 17556205
TI  - "Ratchet" syndrome, another etiology for pacemaker lead dislodgement: a case
      report.

PMID- 17556206
TI  - New concepts for old drugs to maintain sinus rhythm in patients with atrial
      fibrillation.
AB  - Atrial fibrillation (AF) is a chronic, often progressive disease. Despite the
      ongoing concerted effort to improve AF therapy, often there is no remedy for
      curing AF and preventing the deleterious effects of the arrhythmia on health.
      Antiarrhythmic drug therapy is likely to remain the mainstay of therapy for many
      patients in the foreseeable future. Available antiarrhythmic drugs are moderately
      effective, which is important for patients who respond, especially given the
      chronic and often progressive nature of the disease. This article describes
      emerging concepts under clinical evaluation that attempt to improve the safety of
      available antiarrhythmic drugs in the treatment of recurrent AF. Two concepts are
      reviewed: (1) combination of an antiarrhythmic drug with a calcium channel
      blocker to reduce proarrhythmic side effects, and (2) "intelligent" reduction of
      the duration of antiarrhythmic drug therapy targeted to periods of symptomatic or
      likely AF recurrence.

PMID- 17556207
TI  - The molecular basis of catecholaminergic polymorphic ventricular tachycardia:
      what are the different hypotheses regarding mechanisms?

PMID- 17556208
TI  - Paroxysmal supraventricular tachycardia: what is the mechanism?

PMID- 17556209
TI  - Unusual atrial-paced tachycardia after pacemaker implantation: what is the
      mechanism?

PMID- 17556210
TI  - How to perform linear lesions.

PMID- 17556211
TI  - Persistent left superior vena cava opening directly into right atrium and
      mistaken for coronary sinus during biventricular pacemaker implantation.

PMID- 17556212
TI  - Clinical considerations for allied professionals: issues in transition to adult
      congenital heart disease programs.

PMID- 17556213
TI  - HRS/EHRA/ECAS expert Consensus Statement on catheter and surgical ablation of
      atrial fibrillation: recommendations for personnel, policy, procedures and follow
      up. A report of the Heart Rhythm Society (HRS) Task Force on catheter and
      surgical ablation of atrial fibrillation.

PMID- 17556214
TI  - Cardiac electrophysiology in China.

PMID- 17556215
TI  - [Editorial].

PMID- 17556216
TI  - [Self-consciousness, consciousness of the other and dementias].
AB  - Studies of self-consciousness in dementia concern essentially anosognosia or the
      loss of insight. However, Self-consciousness is multifaceted: it includes
      awareness of the body, perceptions, one's own history, identity, and one's own
      projects. Self-consciousness is linked to consciousness of others i.e. to social
      cognition supported by identification of others, but also by comprehension of
      facial expression of emotions, comprehension and expression of emotional prosody,
      pragmatic abilities, ability to infer other's people's mental states, thoughts,
      and feelings (theory of mind and empathy), knowledge of social norms and rules,
      social reasoning. The subtypes of dementias (and namely Alzheimer's disease and
      frontotemporal dementia) affect heterogeneously the different aspects of the self
      and other-consciousness. Further studies are needed for a better knowledge of the
      complex relationship between Self-consciousness, social cognition, decision
      making and neuropsychiatric symptoms and behavioral disturbances occurring in
      demented patients.

PMID- 17556217
TI  - [Loss of consciousness in the elderly].
AB  - Syncope combines loss of consciousness and inability to maintain postural tone.
      Prevalence in the subjects aged of 70 years and older is near 30%. In most cases,
      several causes lead to syncope. The main mechanisms are heart disease,
      dysautonomy and miscellaneous conditions like anemia varicosis, or drugs with
      anticholinergic effects. Anamnesis and physical examination lead to the diagnosis
      in up to 50%. The decision for further diagnostic tests often depends on the
      evidence of an underlying heart disease. Blood tests, ECG and search of arterial
      hypotension must be systematically performed. In absence of diagnosis, prolonged
      ECG monitoring and echocardiography, are the second step exploration. Then tilt
      test, cardiac electrophysiological study, electroencephalogram may be discussed
      according to the efficient strategy for the patient. The most important step is
      to diagnose heart disease because the mortality is doubled in these cases. About
      10% of syncopes remained unexplained in the elderly. But their prognosis is not
      significantly different from that of syncopes of non cardiac origin. So there is
      no reason to perform invasive explorations to discover etiology in this context.
      For elderly patients admitted in an emergency ward, the San Francisco Rule aids
      physician's decision making and performs better than current physician
      performance to predict prognosis in the first week after syncope. Protocol care
      must to be developed in geriatric institutions to increase the quality of
      diagnosis and treatment of elderly subjects after loss of consciousness.

PMID- 17556218
TI  - [Alzheimer's disease, hearing impairment and hearing-aids: a review].
AB  - Alzheimer's disease has major social and family consequences. However,
      therapeutic strategies are still limited. Non-pharmacological therapeutic
      approaches are known to be useful to protect the intellectual abilities of the
      patients, or at least, to slow down their decline. Therefore, it is important to
      pay attention to the consequences of sensory impairment in these old patients.
      Indeed, sensory troubles, mainly concerning hearing, may have an impact on the
      cognitive and behavioral symptoms. Several studies showed that the management of
      hearing impairment could afford cognitive and behavioral benefits in demented
      subjects as well as for the non-demented people. These results are encouraging,
      and suggest that hearing management should be applied to all hearing impaired
      patients with Alzheimer's disease.

PMID- 17556219
TI  - [Semantic dementia].
AB  - Semantic dementia (SD) is characterized by an assymetric atrophy of the temporal
      lobes and, clinically, by an impairment of the semantic memory associated to
      psychobehavioral symptoms. The concept of SD was defined in 1989 and still
      remains controversial. Some authors consider DS as a specific entity, others as
      part of the frontotemporal dementia (FTD) or a variant of the progressive aphasia
      syndrome. Many arguments tend to include SD in the FTD. However, SD presents a
      high interest for the comprehension of the organization of semantic memory in
      man, and is often associated with specific histopathologic lesions (ubiquitine
      positive and tau negative). Therefore SD should be considered as a clinical
      specific entity.

PMID- 17556220
TI  - [Nurses in geriatrics and Alzheimer's disease: knowledge, image, and common
      practice-results from a survey in a French area (Alsace)].
AB  - From the data of a multicentric investigation, performed in a French area
      (Alsace) using questionnaires filled by 800 geriatrics nurses, the author
      analyses their current knowledge and representations of Alzheimer's disease,
      their attitudes and practice concerning the disclosure of the diagnosis to the
      patients, and the influence of these data for the patients care. The results show
      three principal common aspects: first very important gaps, difficulties and
      contradictions concerning Alzheimer's disease knowledge; then heavy feelings of
      incompetence, loneliness, and therapeutic inanity with regard to the problems of
      their practice; last of all, their requests insisting on their need of
      information, formation, and aid, all missing for them. The nurses' language was
      devoid of specific and professional contents. It was similar to the general
      public, mediatic, and societal speeches, loaded with aprioristic assertions,
      reducing Alzheimer's disease to an organic process of humanity decline. This
      alarming picture calls to question its ground, mechanisms and solutions
      concerning the needs conveyed by the nurses, and the pertinency of the common
      concept of Alzheimer's disease. It enjoins to reconsider the nurses formation and
      a transdisciplinar further reflection about the notion of Alzheimer's disease and
      the messages which are transmitted by it.

PMID- 17556221
TI  - [Assessment of cognitive complaints and depressive symptoms in health check-up
      centers].
AB  - Memory clinics, where cognitive impairment is diagnosed, have to deal with an
      increasing number of requests. In this context, this study was aimed to evaluate
      the feasibility of cognitive complaint assessment in a health check-up performed
      in preventive Health check-up centers. METHODS: The study population included 60
      year and over subjects who were proposed a health check-up in the Health check-up
      centers of five French cities (Amiens, Nimes, Longwy, Rennes and Selestat).
      Cognitive complaint and anxio-depressive symptoms were collected for all
      participants. Subjects presenting a cognitive complaint fulfilled a
      neuropsychological screening including MMSE, 5-word test, Clock Drawing test,
      verbal fluencies and exploration of 4 Instrumental Activities of Daily Living.
      Subjects suspected to have cognitive impairment were then referred to a memory
      clinic. RESULTS: One thousand and twenty participants were included in the study;
      31.5% had a cognitive complaint, and 12.3% of these subjects were referred to a
      memory clinic. A dementia was diagnosed in one third of them, corresponding to 1%
      of the study participants. However, all the patients with dementia were referred
      by the same check-up centre, which staff was well experienced in cognitive
      disorders. Moreover, 29.3% of the participants had a depressive symptomatology.
      CONCLUSION: exploration of cognitive functions in a preventive health check-up
      center for elderly people can be interesting, but requires a staff's former
      experience in cognitive disorders, especially for the diagnosis of Mild Cognitive
      Impairment. Moreover, depressive symptoms, which are frequent and can be cared
      for, should be explored in a health check-up for senior citizens.

PMID- 17556222
TI  - Abstracts from the 2nd North American Chapter Meeting and the 1st Latin American
      Chapter Meeting of the International Society for Peritoneal Dialysis. June 1-3,
      2007. Hollywood, Florida, USA.

PMID- 17556287
TI  - Glycosaminoglycans and proteoglycans: overlooked entities?
AB  - BACKGROUND: By virtue of their high net negative charge, glycosaminoglycans and
      proteoglycans play pivotal roles in biologic processes such as cell-cell and cell
      matrix interactions, sequestration of growth factors, activation of chemokines
      and cytokines, and permselectivity of basement membranes. METHODS: The present
      article reviews the putative roles of glycosaminoglycans and proteoglycans in the
      peritoneal cavity during normal peritoneal homeostasis and chronic inflammation,
      the latter induced by constant exposure of the peritoneum to non-physiologic
      peritoneal dialysis (PD) solutions. RESULTS: Glycosaminoglycans have been
      identified in the mesothelial glycocalyx, a slippery, non-adhesive layer that
      protects the peritoneal membrane from abrasion and infection. Dermatan sulfate
      proteoglycans can neutralize the activity of transforming growth factor beta1 and
      can thus play an essential role in modulating peritoneal fibrosis. Heparan
      sulfate proteoglycans play a crucial role in the sequestration of growth factors;
      they also modulate selective permeability of proteins across the peritoneal
      cavity. Reduced expression of perlecan, a heparan sulfate proteoglycan of the
      basement membrane, is observed in peritoneal biopsies obtained from established
      PD patients, consequent to prolonged exposure to the elevated glucose
      concentrations in conventional PD solutions. Supplementation of PD fluids with
      glycosaminoglycans has been shown to be beneficial to both the structural and
      functional integrity of the peritoneum. CONCLUSIONS: Recent advances in the field
      of glycobiology have revealed a multitude of biologic processes that are
      controlled or influenced by glycosaminoglycans and proteoglycans. Altered
      synthesis of these macromolecules during PD has serious implications for the
      peritoneal transport of proteins, host defense, wound healing, inflammation, and
      fibrosis.

PMID- 17556288
TI  - Mesothelial cells.
AB  - BACKGROUND: The introduction of peritoneal dialysis (PD) as a modality of renal
      replacement therapy has provoked much interest in the biology of the peritoneal
      mesothelial cell. Mesothelial cells isolated from omental tissue have
      immunohistochemical markers that are identical to those of mesothelial stem
      cells, and omental mesothelial cells can be cultivated in vitro to study changes
      to their biologic functions in the setting of PD. METHOD: The present article
      describes the structure and function of mesothelial cells in the normal
      peritoneum and details the morphologic changes that occur after the introduction
      of PD. Furthermore, this article reviews the literature of mesothelial cell
      culture and the limitations of in vitro studies. RESULTS: The mesothelium is now
      considered to be a dynamic membrane that plays a pivotal role in the homeostasis
      of the peritoneal cavity, contributing to the control of fluid and solute
      transport, inflammation, and wound healing. These functional properties of the
      mesothelium are compromised in the setting of PD. Cultures of peritoneal
      mesothelial cells from omental tissue provide a relevant in vitro model that
      allows researchers to assess specific molecular pathways of disease in a distinct
      population of cells. Structural and functional attributes of mesothelial cells
      are discussed in relation to long-term culture, proliferation potential, age of
      tissue donor, use of human or animal in vitro models, and how the foregoing
      factors may influence in vitro data. CONCLUSIONS: The ability to propagate
      mesothelial cells in culture has resulted, over the past two decades, in an
      explosion of mesothelial cell research pertaining to PD and peritoneal disorders.
      Independent researchers have highlighted the potential use of mesothelial cells
      as targets for gene therapy or transplantation in the search to provide
      therapeutic strategies for the preservation of the mesothelium during chemical or
      bacterial injury.

PMID- 17556289
TI  - Rational choice of peritoneal dialysis catheter.
AB  - The peritoneal catheter should be a permanent and safe access to the peritoneal
      cavity. Catheter-related problems are often the cause of permanent transfer to
      hemodialysis (HD) in up to 20% of peritoneal dialysis (PD) patients; in some
      cases, these problems require a temporary period on HD. Advances in connectology
      have reduced the incidence of peritonitis, and so catheter-related complications
      during PD have become a major concern. In the last few years, novel techniques
      have emerged in the field of PD: new dialysis solutions, better connectology, and
      cyclers for automated PD. However, extracorporeal dialysis has continued to
      improve in terms of methods and patient survival, but PD has failed to do so. The
      main reason is that peritoneal access has remained problematical. The peritoneal
      catheter is the major obstacle to wide-spread use of PD. Overcoming catheter
      related problems means giving a real chance to development of the peritoneal
      technique. Catheters should be as efficient, safe, and acceptable as possible.
      Since its introduction in the mid-1960s, the Tenckhoff catheter has not become
      obsolete: dozens of new models have been proposed, but none has significantly
      reduced the pre-dominance of the first catheter. No convincing prospective data
      demonstrate the superiority of any peritoneal catheter, and so it seems that
      factors other than choice of catheter are what affect survival and complication
      rates. Efforts to improve peritoneal catheter survival and complication rates
      should probably focus on factors other than the choice of catheter. The present
      article provides an overview of the characteristics of the best-known peritoneal
      catheters.

PMID- 17556290
TI  - Clinical effects of combined therapy with peritoneal dialysis and hemodialysis.
AB  - The fundamental objective of dialysis is to maintain the dose of solute clearance
      and ultrafiltration (UF). When peritoneal dialysis (PD) patients cannot maintain
      target clearances, the dialysis dose needs to be increased. The means of
      increasing dose by PD alone are limited, especially in patients with UF failure.
      Combination therapy with PD and hemodialysis (PD+HD) is the simplest way to solve
      this problem. The general prescription for PD+HD should be 5-6 days of PD and 1
      session of HD weekly. To determine the adequacy of PD+HD, we adopted the
      equivalent renal clearance (EKR), transforming the weekly Kt/V from PD and then
      evaluating the total clearance from both modalities. The weekly PD+HD regimen
      improves clinical status in patients in whom PD alone does not result in dialysis
      adequacy, and it permits a substantial prolongation of PD. The complementary
      effects of PD and HD improve clinical status and prognosis in patients undergoing
      dialysis; we therefore propose to use the term "complementary dialysis" for this
      technique.

PMID- 17556291
TI  - Advances in the technology of automated, tidal, and continuous flow peritoneal
      dialysis.
AB  - Automated peritoneal dialysis (APD) has undergone substantial growth in recent
      years because of an increased demand for higher doses of peritoneal dialysis (PD)
      treatment and a need to improve quality of life for patients. The evolution of
      this treatment is closely linked with the development of new automatic machines
      and with recent advances in prescription and monitoring of PD treatment. In the
      present article, we describe the characteristics of the new generation of APD
      cyclers with particular regard to adequacy targets and safety. There is renewed
      interest in continuous-flow peritoneal dialysis (CFPD), because of a belief that
      new peritoneal access technologies will make the success of this modality a
      possibility. In the CFPD technique, a certain amount of fluid is constantly
      present in the abdomen, and constant inflow and outflow are maintained without
      interruption thanks to paired indwelling catheters. The PD solution is used
      either in a single pass or in a recirculation loop with a regeneration systems
      (sorbent cartridge or dialyzer).

PMID- 17556292
TI  - Automated peritoneal dialysis in children and adolescents--benefits: a survey of
      patients and parents on health-related quality of life.
AB  - Automated peritoneal dialysis (APD) benefits children on dialysis and their
      parents by allowing for more daytime freedom and a more normal life. We carried
      out a survey on health-related quality of life (HRQOL) in children and
      adolescents from our end-stage renal disease program, including those on APD and
      hemodialysis (HD), and those who had received a kidney transplant (TX). Parents
      of patients under 18 years of age were also interviewed. The questionnaire on QOL
      was adapted from the Pediatric Quality of Life Inventory and grouped into seven
      aspects for which patients and parents were asked to assess the frequency of
      related problems during the preceding 3 months. We surveyed eligible children
      among the APD, HD, and TX patients enrolled in our program, and we surveyed the
      parents of the patients under 18 years of age. For APD, patients and parents both
      gave their most favorable scores to the peer activities and relationships and
      family activities and relationships aspects. In the TX group, the family
      activities and relationships aspect was also scored most favorably of all
      aspects. Notably, we observed no significant difference between the total scores
      for the APD and TX groups among patients and parents alike. Although the survey
      provided only a "snapshot" of HRQOL, the assessment by APD patients and their
      parents seems to be comparable to that by TX patients and their parents.

PMID- 17556293
TI  - Methodology of assessment of fluid status and ultrafiltration problems.
AB  - Loss of sodium and water excretion with disruption of volume homeostasis is a
      crucial abnormality of end-stage renal failure. Fluid management is a fundamental
      function of dialysis therapy, but studies show frequent occult fluid overload,
      hypertension, and cardiac dysfunction in peritoneal dialysis. A rigorous approach
      to fluid management in PD can achieve excellent fluid, hypertension, and
      cardiovascular results in clinical practice. The present article explores the
      reasons for fluid overload and poor ultrafiltration in peritoneal dialysis
      patients and discusses optimal assessment and management of these problems.

PMID- 17556294
TI  - Maximizing the success of peritoneal dialysis in high transporters.
AB  - This article reviews the current understanding of high transport status in the
      peritoneal dialysis population and emphasizes survival can be improved for high
      transporters. To address the current state of knowledge on high peritoneal
      membrane transport, the negative impact of an increased peritoneal solute
      transport rate is first discussed. The potential downside of high transport
      status, notably on survival outcomes (as supported by registry data and meta
      analysis), is highlighted. Based on recent advances and clinical studies, ways of
      maximizing the success of peritoneal dialysis treatment in high transporters are
      discussed, and management strategies are proposed.

PMID- 17556295
TI  - Continuous ambulatory peritoneal dialysis is better than automated peritoneal
      dialysis as first-line treatment in renal replacement therapy.
AB  - This article examines the roles of continuous ambulatory peritoneal dialysis
      (CAPD) versus automated peritoneal dialysis (APD) as first-line renal replacement
      therapy. To date, no high-quality large-scale randomized controlled studies have
      compared CAPD with APD as first-line therapy. However, a discussion on this issue
      is important so that nephrologists can decide and patients can have a choice of
      modality on which to start dialysis, especially in the context of health care
      economics. We review the literature and present Hong Kong as the model of a "CAPD
      first" policy, an appealing, cost-effective approach for any country. An ideal
      renal replacement therapy should provide optimal survival, lowest possible risk
      for comorbidity, highest level of quality of life, and equally important,
      acceptable cost to society. When we consider this subject in the context that all
      patients should be started on one first-line modality, the data suggest that a
      "CAPD first" policy has all these advantages, with APD probably having the edge
      only with regard to patient preference. The present review highlights
      preservation of residual renal function, removal and balancing of sodium,
      incidence of peritonitis, peritoneal membrane transport status, patient
      rehabilitation, and financial issues in demonstrating that a "CAPD first" policy
      is the model that should be adopted.

PMID- 17556296
TI  - Therapeutic options for preservation of residual renal function in patients on
      peritoneal dialysis.
AB  - Dialysis is not the ideal renal replacement therapy because it does not fully
      restore all kidney functions. Increasing evidence suggests that preservation of
      residual renal function is associated with a survival benefit, a decrease in
      morbidity, better nutrition, a lower level of inflammatory markers, an improved
      quality of life, and cost savings by obviating the need for more peritoneal
      dialysis exchanges and possibly by reducing the requirement for antihypertensive
      agents, phosphate binders, and erythropoietin. In the present article, we review
      the impact of residual renal function on patient outcomes and the renoprotective
      strategies available in patients on peritoneal dialysis.

PMID- 17556297
TI  - Quality assurance in peritoneal dialysis.
AB  - The present article reviews current treatment targets for peritoneal dialysis
      (PD) and the various methods for evaluating adequacy with time on PD.

PMID- 17556298
TI  - Adequacy of peritoneal dialysis in children: consider the membrane for optimal
      prescription.
AB  - The peritoneal dialysis (PD) prescription should be adequate before being
      optimal. The peritoneal membrane is a dynamic dialyzer: the surface area and the
      vascular area both have recruitment capacity. At bedside, prescription is based
      mainly on tolerance of the prescribed fill volume, and therefore a too-small fill
      volume is often prescribed. A too-small fill volume may lead to a hyperpermeable
      exchange, with potentially enhanced morbidity-or even mortality-risks. Better
      understanding of the peritoneal membrane as a dynamic dialysis surface area
      allows for an individually adapted prescription, which is especially suitable for
      children on automated PD. Fill volume should be scaled for body surface area
      (mL/m2) and, to avoid a hyperpermeable exchange, for a not-too-small amount. Fill
      volume enhancement should be conducted under clinical control and is best
      determined by intraperitoneal pressure measurement in centimeters of H2O. In
      children 2 years of age and older, a peak fill volume of 1400-1500 mL/m2 can be
      prescribed in terms of tolerance, efficiency, and peritoneal membrane
      recruitment. Dwell times should be determined individually with respect to two
      opposing parameters: Short dwell times provide adequate small-solute clearance
      and maintain the crystalloid osmotic gradient (and, thereby, the ultrafiltration
      capacity). Long dwell times enhance phosphate clearance, but can lead to
      dialysate reabsorption. The new PD fluids (that is, those free of glucose
      degradation products, with a neutral pH, and not exclusively lactate-buffered)
      appear to be the best choice both in terms of membrane recruitment and of
      preservation of peritoneal vascular hyperperfusion.

PMID- 17556299
TI  - Can we overcome the predestined poor survival of diabetic patients? Perspectives
      from pre- and post-dialysis.
AB  - Although the survival of diabetic peritoneal dialysis (PD) patients has improved,
      it is still much worse than the survival of nondiabetic patients. Diabetes has
      its own risks for cardiovascular disease (CVD), such as increased levels of
      advanced glycation end-products, carbonyl and oxidative stress, and low-grade
      inflammation. An independent, graded association has been observed between a
      reduced glomerular filtration rate and the risk of CVD events in chronic kidney
      disease (CKD). Both CKD and diabetes synergistically lead to a high risk of CVD.
      It seems that the poor survival of diabetic PD patients is predestined at the
      initiation of dialysis because of multiple pre-existing risk factors and comorbid
      diseases, particularly CVD. Recently, several trials were successful in improving
      the survival of patients with diabetic CKD. Tight control of glucose, blood
      pressure management using angiotensin converting-enzyme inhibitors or angiotensin
      II receptor blockers, and use of statins, antioxidants, or peroxisome
      proliferator-activated receptor gamma agonists may improve the survival of
      diabetic PD patients. However, simple correction of a single CVD risk factor is
      not likely to be effective. New PD solutions such as those low in glucose
      degradation products or those with icodextrin may also be effective in reducing
      the risk of CVD in diabetic PD patients. Therefore, multifactorial interventions-
      including diet control, early referral, and choice of an optimal PD solution--may
      improve the survival of diabetic PD patients.

PMID- 17556300
TI  - Treatment targets for diabetic patients on peritoneal dialysis: any evidence?
AB  - Diabetic patients are often affected by comorbid conditions that influence
      clinical outcome. Taking care of diabetic peritoneal dialysis (PD) patients is a
      challenge for nephrologists, not only because these patients have more
      complications and comorbidities, but also because of their difficulties in
      maintaining glycemic control with the use of current glucose-containing dialysis
      solutions. In addition, the increased transport of small molecules and proteins
      by the peritoneal membrane in diabetic patients adds the further problems of
      ultrafiltration deficit and malnutrition. The present article reviews pertinent
      evidence toward establishing the best strategy for the care of diabetic PD
      patients. With better glycemic control, improved nutrition, improved fluid
      balance, and optimal preservation of residual renal function, there is hope for
      improving the survival of diabetic PD patients.

PMID- 17556301
TI  - Long-term peritoneal dialysis in infants.
AB  - Although the numbers of infants requiring dialysis are small, management of these
      patients presents many challenges. Mortality is high in infants with
      comorbidities, complications of dialysis are common, and most of these infants
      need enteral feeding. However, the long-term outcome for otherwise healthy
      infants is comparable to that for older children.

PMID- 17556302
TI  - How to improve survival in geriatric peritoneal dialysis patients.
AB  - BACKGROUND: Recently, more elderly patients who are independent or able to live
      at home with the support of family are opting for continuous ambulatory
      peritoneal dialysis (CAPD). At the end of 2005, the annual statistical survey
      conducted by the Japanese Society for Dialysis Therapy indicated that the mean
      age of patients at initiation of dialysis treatment is 66.2 years. Only 3.6% of
      the overall end-stage renal disease population were treated with CAPD, and this
      small number of elderly patients was treated with CAPD despite the many merits of
      peritoneal dialysis (PD) for the elderly. In the present study, we reviewed our
      experience with patients 65 years of age and older at the start of PD and the
      results from two multicenter studies on PD treatment in elderly patients in
      Japan. PATIENTS AND METHODS: Study 1: Of 313 PD patients at Okayama Saiseikai
      General Hospital between January 1991 and June 2006, 166 patients 65 years of age
      and older were studied. The characteristics of these elderly PD patients were
      reviewed to determine which elderly patients can continue PD for more than 5
      years, and what the causes of death and the effects of icodextrin were in elderly
      PD patients. Study 2: A multicenter study of 421 patients introduced to PD from
      April 2000 to December 2004 in Japan was carried out by the Japanese Society for
      Elderly Patients on Peritoneal Dialysis to retrospectively analyze patient
      survival and technique survival and to find factors that have the potential to
      influence prognosis in these patients. Study 3: A review of the PD management and
      nursing-care insurance system (long-term care insurance) targeted patients 65
      years of age and older who were initiated onto PD from January 2000 to June 2002
      at 82 centers in Japan. The review found 765 patients under the age of 65 years
      (62.6%), and 458 patients 65 years of age and over (37.4%). Data on 409 elderly
      PD patients from 73 centers were analyzed. RESULTS: Study 1: In 166 elderly
      patients, 27 (16.3%; 18 women, 9 men) continued PD for more than 5 years at our
      hospital. The original disease was chronic glomerulonephritis in 21 patients,
      diabetic nephropathy in 2 patients, nephrosclerosis in 2 patients, and polycystic
      kidney disease in 2 patients. The causes of death in the elderly PD patients at
      our hospital were heart failure (20.3%), cerebrovascular disease (17.7%),
      myocardial infarction (15.2%), debilitation (12.7%), peritonitis (7.6%), and
      pneumonia (3.8%). We observed significant differences in ultrafiltration, body
      weight, sodium, chloride, red blood cells, and hematocrit after using icodextrin
      in 14 elderly PD patients. Also, use of icodextrin in the daytime helps the
      family supporting an elderly member on PD by reducing the number of exchanges.
      Study 2: The average age of 421 patients in 37 hospitals throughout Japan was
      76.4 years. Women accounted for 41% of all patients. The average modified
      (exclusive of factors of aging) Charlson comorbidity index (CCI) was 3.7. The
      modified CCI was an important factor not only in patient survival but also in
      technique survival. Patient survival was significantly different for the three
      modified CCI groups (CCI<3, 3<or=CCI<5, 5<or=CCI). Factors that influenced
      patient survival included patient choice of modality, modified CCI, exchanges
      performed by family members, and age at the start of PD. Factors that influenced
      technique survival included patient choice of modality, modified CCI, and
      exchanges performed by family members. Age at the start of PD was not a
      significant factor influencing technique survival. Study 3: Most elderly PD
      patients were living with family; 7% were living alone. At the start of PD, 24%
      of elderly PD patients were covered by nursing-care insurance, including 11% of
      young elderly patients (65-74 years of age), 35% of old elderly patients (75-84
      years of age), and 29% of very old elderly patients (85 years of age or older).
      Patients 75 years of age or older were covered by nursing-care insurance more
      frequently than were patients under 75 years of age. Nevertheless, at the start
      of dialysis, fewer than 10% of elderly patients were using nursing-care insurance
      for PD. CONCLUSIONS: In elderly patients, PD has good outcomes, especially in
      nondiabetic patients, in patients with few comorbidities, and in patients
      managing PD by themselves. In introducing dialysis in elderly patients, PD should
      be the treatment of choice. A more secure support system should be established to
      allow the elderly to choose PD treatment.

PMID- 17556303
TI  - Peritoneal dialysis in patients with diabetes: are the benefits greater than the
      disadvantages?
AB  - Diabetic nephropathy has been increasing in prevalence in recent years, and it is
      now the dominant cause of end-stage renal disease (ESRD) worldwide. Because
      diabetes is frequently associated with multiple complications, nephrologists must
      be alert to the selection of dialysis modality so as to reduce the accompanying
      risks. The present review addresses whether the benefits of peritoneal dialysis
      are greater than its disadvantages in diabetic patients. The answer is quite
      positive: for most diabetic patients, peritoneal dialysis offers multiple
      benefits.

PMID- 17556304
TI  - Good patient and technique survival in elderly patients on continuous ambulatory
      peritoneal dialysis.
AB  - The aging population has significant implications for the community. The
      increasing number of elderly end-stage renal disease (ESRD) patients presses the
      renal team to find an appropriate management plan. We used a retrospective
      analysis to study the effectiveness of continuous ambulatory peritoneal dialysis
      (CAPD) in elderly ESRD patients. Of the 328 CAPD patients recruited for the
      study, 121 were in the elderly group (>or=65 years of age), and 207 were in the
      control group (under 65 years of age). Median age in the elderly group was 71
      years, and in the control group, 51 years. The elderly group had a higher
      prevalence (54.5%) of diabetes mellitus. The 2-year and 5-year rates of patient
      survival were 89.3% and 54.8% respectively in the elderly group and 92.2% and
      62.9% in the control group (p=0.19). The 2-year and 5-year rates of technique
      survival were 84.0% and 45.7% respectively in the elderly group and 80.9% and
      49.1% in the control group (p=0.75). The probability of a 12-month peritonitis
      free period was 76.6% in the elderly group and 76.5% in the control group
      (p=0.75). One hundred elderly patients (82.6% of the group) performed their CAPD
      exchanges by themselves. We observed no significant difference in clinical
      outcome-including patient survival, technique survival, and peritonitis-free
      period-between the elderly self-care CAPD and the elderly assisted CAPD groups.
      In elderly ESRD patients, CAPD is an effective dialysis modality. A slightly
      longer training time is to be expected for elderly patients. Self-care CAPD for
      elderly patients who are capable of performing their own exchanges provides them
      with an independent home life.

PMID- 17556305
TI  - Risk factors for cardiovascular disease in patients undergoing peritoneal
      dialysis.
AB  - Patients on peritoneal dialysis (PD) are at high cardiovascular risk. Although
      some risk factors are unmodifiable (for example, age, sex, genetics), others are
      exacerbated in the unfriendly uremic milieu (inflammation, oxidative stress,
      mineral disturbances) or contribute per se to kidney disease and cardiovascular
      progression (diabetes mellitus, hypertension). Moreover, several factors
      associated with PD therapy may both increase (by altered lipid profile,
      hyperinsulinemia, and formation of advanced glycation end-products) and decrease
      (by better blood pressure control and anemia management) cardiovascular risk. The
      present review discusses recent findings and therapy trends in cardiovascular
      research on the PD population, with emphasis on the roles of inflammation,
      insulin resistance, homocysteinemia, dyslipidemia, vascular calcification, and
      genetics/epigenetics.

PMID- 17556306
TI  - Telemedicine system for patients on continuous ambulatory peritoneal dialysis.
AB  - Over recent decades, rapid progress in information and telecommunications
      technology has led to the application of these technologies in the medical field.
      In 1999, we reported on a telemedicine system (version 1.0) that used an
      automated peritoneal dialysis machine to collect data on patients with end-stage
      renal disease. After 2002, we focused on using cellular telephones in a new
      telemedicine system (version 2.0) to monitor patient data at home, including
      blood pressure (BP), heart rate, body weight, urine volume, and blood glucose. By
      2003, we had developed a fully automatic system called I-converter (version 3.0)
      to collect data from a fully automatic device and send it via cellular telephone.
      After the fully automatic device measures a patient's BP, I-converter sends the
      data directly to the main server in our central data center. That server is
      directly connected to Web site by application service provider (ASP) technology.
      Recently, to make the system simpler, we developed a new version called D
      converter (version 4.0). The telephone used in this new system is a Personal
      Handy-phone System (PHS). The PHS has several advantages: high-speed data
      transmission, low power output, little electromagnetic interference with medical
      devices, and easy locating of patients. The D-converter system uses a small
      computer and a PHS card called a Dopa card. Our telemedicine systems monitor
      continuous ambulatory peritoneal dialysis (CAPD) patients at home. For elderly
      and handicapped patients, these systems are very advantageous because they reduce
      visits to the outpatient clinic. In addition, data can be monitored at the
      patient's home in real time. The present paper reports our recent advances in
      telemedicine systems for CAPD patients.

PMID- 17556307
TI  - Peripheral vascular disease in diabetic peritoneal dialysis patients.
AB  - In the present article, we review current knowledge of the epidemiology,
      diagnosis, and treatment of peripheral vascular disease in patients with end
      stage renal disease. The main focus is placed on diabetic patients receiving
      peritoneal dialysis, but studies on patients receiving hemodialysis are also
      reviewed, because most reports involve this patient group, and the number of
      reports on peripheral vascular disease in PD patients alone is limited.

PMID- 17556308
TI  - An overview of the pathophysiology of vascular calcification in chronic kidney
      disease.
AB  - Abnormalities of calcium-phosphate balance, with subsequent bone metabolism
      disorders, are among the key and earliest features of chronic kidney disease
      (CKD). Recently, another consequence of these abnormalities was brought to light
      namely, vascular calcification. Most studies performed in patients on dialysis
      suggest that their vascular calcification is more advanced than that seen in the
      general population. Furthermore, the progression of vessel wall mineralization is
      much more dynamic in patients with CKD. Apart from the commonly assessed factors
      that promote vascular calcification, such as age, duration of dialysis, or poor
      control of calcium-phosphate status, several other factors have recently been
      identified. In the spectrum of substances involved in the regulation of the
      process of soft-tissue calcification, the most extensively studied in the
      nephrology literature are bone morphogenetic protein 7, osteoprotegerin, matrix
      Gla protein, fetuin-A, and the phosphatonins. Better understanding of the
      mechanisms underlying excess vascular mineralization have led to the development
      of promising new therapies.

PMID- 17556309
TI  - Cardiovascular risk factors in peritoneal dialysis patients revisited.
AB  - End-stage renal disease patients are at a heightened risk of developing
      cardiovascular disease, with contributions from both "traditional" and
      "nontraditional" cardiovascular risk factors. Some of the nontraditional risk
      factors, such as extracellular volume overload, inflammation, and
      hyperphosphatemia, have also been shown to be important predictors of mortality
      in the dialysis population. This article provides an in-depth review of the
      evidence that supports the substantial contributions of nontraditional risk
      factors to adverse cardiovascular outcomes in chronic peritoneal dialysis
      patients. In addition, it provides evidence to demonstrate how loss of residual
      renal function may be central to the development of cardiovascular disease in the
      peritoneal dialysis population.

PMID- 17556310
TI  - The "heart" of peritoneal dialysis.
AB  - Cardiovascular disease accounts for more than half of all deaths in end-stage
      renal disease patients receiving chronic peritoneal dialysis (PD) treatment. The
      recent demonstration of the important association between residual renal
      clearance (but not PD clearance) and overall and cardiovascular survival in
      chronic PD patients has led us to further explore the mechanisms that can
      potentially explain the close link between residual renal function and
      cardiovascular disease in this population. This John Maher Award Lecture provides
      a review of my own work and that of other groups that provides support for the
      importance of residual renal function not only in providing small-solute
      clearance but also in maintaining the cardiovascular health, nutrition status,
      and wellbeing of PD patients. Data are provided to demonstrate why preservation
      of residual renal function may be the key to improving survival and
      cardiovascular outcomes in PD patients.

PMID- 17556311
TI  - Association of carnitine deficiency in Indian continuous ambulatory peritoneal
      dialysis patients with anemia, erythropoietin use, residual renal function, and
      diabetes mellitus.
AB  - OBJECTIVE: In the present study, we aimed to determine levels of free carnitine
      in hemodialysis (HD) and peritoneal dialysis (PD) patients in India and to
      correlate carnitine deficiency with various clinical parameters. METHODS:
      Patients on HD and PD at two tertiary care centers were selected for the study.
      Baseline data were obtained, and a free carnitine analysis was performed.
      Carnitine deficiency was defined as a free carnitine level of less than 40
      micromol/L. RESULTS: The total number of study patients was 96 (77 on HD, 19 on
      PD). In the PD group, the mean age was 56 years, with 26.3% of the patients being
      vegan, 47.4% having diabetes, and 57.9% having a daily urine output of <500 mL.
      The mean carnitine level in that group was 38.9 micromol/L, and 68.4% of the
      patients had a carnitine deficiency. A Pearson correlation test failed to show
      any association of carnitine level with parameters such as anemia, use of
      erythropoietin, non-vegetarian diet, diabetes, and hypertension. In the HD group,
      the mean age was 45 years, with 22% of the patients being vegan, 23% having
      diabetes, and 45.5% having a daily urine output of <500 mL. The mean carnitine
      level in the group was 38.2 micromol/L, and 64.3% of the patients had a carnitine
      deficiency. Residual renal function and duration of dialysis were different in HD
      patients with and without carnitine deficiency. Carnitine levels in the HD group
      correlated positively and statistically significantly with the presence of
      diabetes and hypertension. CONCLUSION: This study is the first demonstration that
      Indian dialysis patients have carnitine deficiency.

PMID- 17556312
TI  - Identifying and managing malnutrition stemming from different causes.
AB  - Protein-energy malnutrition (PEM) is highly prevalent among peritoneal dialysis
      (PD) patients and is a strong predictor of morbidity and mortality. A wide range
      of factors can lead to PEM and associated wasting (PEM/W) in PD patients, but
      persistent inflammation and the presence of diabetes have been identified as the
      two main reasons. An important body of literature has been reporting studies of
      methods suitable for detecting malnutrition in its early phase so that
      appropriate intervention can be provided. Although assessment of nutrition status
      has been substantially improved, no definitive single method of assessing
      nutrition status has been decided. Rather, several different markers of nutrition
      should be evaluated together. Because of the complexity of treating malnutrition
      in PD patients, nontraditional strategies such as appetite stimulants, anti
      inflammatory diets, and anti-inflammatory pharmacologic agents are recommended to
      be combined with more traditional forms of nutritional support, so as to provide
      a better chance of recovery. The present review briefly discusses the causes of
      PEM/W, the methods most commonly used to identify the condition, and the new
      management strategies available.

PMID- 17556313
TI  - Body composition analysis techniques in adult and pediatric patients: how
      reliable are they? How useful are they clinically?
AB  - Complex abnormalities of body composition occur in peritoneal dialysis (PD).
      These abnormalities reflect changes in hydration, nutrition, and body fat, and
      they are of major clinical significance. Clinical assessment of these body
      compartments is insensitive and inaccurate. Frequently, simultaneous changes of
      hydration, wasting, and body fat content can occur, confounding clinical
      assessment of each component. Body composition can be described by models of
      varying complexity that use one or more measurement techniques. "Gold standard"
      methods provide accurate and precise data, but are not practical for routine
      clinical use. Dual energy X-ray absorptiometry allows for measurement of regional
      as well as whole-body composition, which can provide further information of
      clinical relevance. Simpler techniques such as anthropometry and bioelectrical
      impedance analysis are suited to routine use in clinic or at the bedside, but may
      be less accurate. Body composition methodology sometimes makes assumptions
      regarding relationships between components, particularly in regard to hydration,
      which may be invalid in pathologic states. Uncritical application of these
      methods to the PD patient may result in erroneous interpretation of results.
      Understanding the foundations and limitations of body composition techniques
      allows for optimal application in clinical practice.

PMID- 17556314
TI  - What is the optimal fat mass in peritoneal dialysis patients?
AB  - The prevalence of obesity in peritoneal dialysis (PD) populations has risen
      dramatically since the mid-1980s. This epidemic has been driven by the increased
      prevalence of obesity in the general population, the increased risk of
      progression of chronic kidney disease to end-stage renal failure (ESRF) in obese
      subjects, the reduced probability of listing obese dialysis patients for renal
      transplantation, a paradoxical enhanced survival in at least some obese
      populations on dialysis as compared with non-obese ESRF patients, and a possible
      adipogenic effect of excessive peritoneal glucose absorption in PD. Although
      obesity has consistently been associated with improved outcomes in hemodialysis,
      conflicting results have been seen in PD. In general, an elevated body mass index
      (BMI) has been associated with a neutral or deleterious impact on PD outcomes,
      and the relationship appears to be explained predominantly by fat mass. Risk is
      also elevated in patients with a low BMI, such that the "optimal BMI" appears to
      lie between 20 kg/m2 and 25 kg/m2. The mechanisms underpinning the harmful effect
      of obesity appear to include increased peritonitis rate, proinflammatory effects,
      and a more rapid decline of residual renal function in obese patients. No proof
      exists that weight reduction engenders an improvement in outcome in PD patients,
      but the available studies suggest that cautious weight reduction is advisable. A
      few studies have demonstrated that clinically important and sustained weight
      reduction can be successfully achieved through a combination of individual meal
      plans, regular exercise, and substitution of icodextrin for dextrose in the once
      daily long dwell.

PMID- 17556315
TI  - Intravenous versus oral iron supplementation in peritoneal dialysis patients.
AB  - Iron supplementation is required in a preponderance of peritoneal dialysis (PD)
      patients treated with erythropoietic stimulatory agents (ESAs). Although many
      authors and clinical practice guidelines recommend primary oral iron
      supplementation in ESA-treated PD patients, numerous studies have clearly
      demonstrated that, because of a combination of poor bioavailability of oral iron,
      gastrointestinal intolerance, and noncompliance, oral iron supplementation is
      insufficient for maintaining a positive iron balance in these patients over time.
      Controlled trials have demonstrated that, in iron-deficient and iron-replete PD
      patients alike, intravenous (IV) iron supplementation results in superior iron
      stores and hemoglobin levels with fewer side effects than oral iron produces.
      Careful monitoring of iron stores in patients receiving IV iron supplementation
      is important in view of conflicting epidemiologic links between IV iron loading
      and infection and cardiovascular disease. Emerging new iron therapies such as
      heme iron polypeptide and ferumoxytol may further enhance the tolerability,
      efficacy, and ease of administration of iron in PD patients.

PMID- 17556316
TI  - Tuberculous and fungal peritonitis in patients undergoing continuous ambulatory
      peritoneal dialysis.
AB  - Tuberculous and fungal infections are two relatively uncommon but important
      causes of peritonitis in patients undergoing continuous ambulatory peritoneal
      dialysis (CAPD). The clinical features, diagnosis, and management of these two
      special forms of CAPD-related peritonitis are highlighted in this article.

PMID- 17556317
TI  - Gram-negative peritonitis--the Achilles heel of peritoneal dialysis?
AB  - Peritonitis caused by gram-negative bacteria is a serious complication of
      peritoneal dialysis. Antibiotic resistance is common, and response to medical
      treatment is often poor. In the present article, we review recent advances in the
      understanding of the pathogenesis and treatment of this serious condition.

PMID- 17556318
TI  - Our experience of home visits in city and rural areas.
AB  - In a peritoneal dialysis (PD) program, an efficient and well-structured home
      visit schedule is imperative for ensuring patient compliance, adherence to proper
      exchange technique, nutrition status monitoring and intervention, and early
      detection of evolving medical comorbid problems so as to prevent further
      complications. Regular home-visit follow-up of the PD patient directly affects
      technique survival and quality of life. The clinical coordinator is ideally
      placed to be the direct link between the PD center and patients in their
      domiciliary surroundings. This professional plays a crucial role in the success
      of a PD program.

PMID- 17556319
TI  - Evolution of antibiotic resistance mechanisms and their relevance to dialysis
      related infections.
AB  - As the survival of patients with end-stage renal failure has improved, their
      exposure to antibiotics has also increased. Infections, especially peritoneal
      dialysis-related peritonitis, are unavoidable because of lapses in technique and
      the slow worsening of systemic and peritoneal defense associated with aging and
      dialysis. The selective pressure inherent in the use of antibiotics shapes the
      pattern of antibiotic resistance in the bacteria causing peritonitis and
      extraperitoneal infections, and vice versa. Renal function-preserving and non
      ototoxic regimens that incorporate double beta-lactams (first- and third
      generation cephalosporins) for peritonitis have increased the selective pressure
      in favor of methicillin-resistant staphylococci (MRS) and extended-spectrum beta
      lactamase (ESBL)-producing Enterobacteriaceae. Attempts to use the
      fluoroquinolones as alternatives to beta-lactams was met with rocketing quinolone
      resistance. The high incidence of MRS led many nephrologists to use empiric
      vancomycin-until the debut of vancomycin-resistant enterococci. The recent
      emergence of heterogeneous and high-level vancomycin resistance in staphylococci
      (which are especially prevalent in patients on dialysis) calls for further
      prudence in the use of vancomycin. The coming challenges are ESBL-producing
      Enterobacteriaceae with carbapenemase, multi-resistant Pseudomonas, and highly
      virulent community-acquired methicillin-resistant Staphylococcus aureus with
      Panton-Valentine leukocidin. Antibiotic auditing programs and meticulous patient
      training by nurses are the only available defense at the moment. Novel approaches
      such as antibiotic-impregnated Tenckhoff catheters, biocompatible dialysis fluid,
      and peritoneal immuno-augmentation strategies are eagerly awaited.

PMID- 17556320
TI  - Factors contributing to the differences in peritonitis rates between centers and
      regions.
AB  - Despite improvements in connectology, peritoneal dialysis (PD)-associated
      peritonitis contributes significantly to morbidity and modality failure in
      patients maintained on PD therapy. A broad spectrum of organisms-gram-positive,
      gram-negative, fungal, anaerobic-are involved in this complication. In addition,
      a significant percentage of episodes involve polymicrobial and culture-negative
      infection. Technological advances are being developed to minimize the incidence
      of access-related complications such as peritonitis. Many traditional factors
      such as exit-site infection and poor technique have been already identified. In
      the present review, we discuss the geographic, patient selection, and clinical
      issues that can affect peritonitis rates in different areas of the world and in
      different centers in the same area.

PMID- 17556321
TI  - Encapsulating peritoneal sclerosis: prevention and treatment.
AB  - Since the first peritoneal dialysis (PD) patients with encapsulating peritoneal
      sclerosis (EPS) were reported in 1980, EPS has been considered primarily a fatal
      complication. The incidence of EPS in PD patients has been reported to be 2.5%,
      with a negative effect of increasing PD duration (which also augments mortality).
      Because EPS occurs after withdrawal from PD in more than half of all cases,
      strict monitoring is necessary when a long-term PD patient is withdrawn from PD.
      Maintaining patients on standard PD with conventional solutions for more than 8
      years is associated with a substantial risk of EPS development. Treatment
      appropriate to the disease stage is most important in EPS. Basic therapeutic
      strategies for EPS include the appropriate use of steroids. If bowel obstruction
      persists, laparotomy and enterolysis should be performed to achieve a complete
      cure. It is now recognized that EPS need not be a fatal complication of PD.

PMID- 17556322
TI  - Sympathetic hyperactivity--a hidden enemy in chronic kidney disease patients.
AB  - Chronic kidney disease is often characterized by the presence of sympathetic
      hyperactivity. The aim of this brief review is to summarize available knowledge
      on the pathogenesis of sympathetic hyperactivity and to discuss its clinical
      relevance, the consequences of this knowledge for the choice of treatment, and
      the yet unresolved issues.

PMID- 17556323
TI  - Adipokines and gut hormones in end-stage renal disease.
AB  - Cachexia is common in end-stage renal disease (ESRD) patients, and it is an
      important risk factor for poor quality of life and increased mortality and
      morbidity. Chronic inflammation is an important cause of cachexia in ESRD
      patients. In the present review, we examine recent evidence suggesting that
      adipokines or adipocytokines such as leptin, adiponectin, resistin, tumor
      necrosis factor alpha, interleukin-6, and interleukin-1beta may play important
      roles in uremic cachexia. We also review the physiology and the potential roles
      of gut hormones, including ghrelin, peptide YY, and cholecystokinin in ESRD.
      Understanding the molecular pathophysiology of these novel hormones in ESRD may
      lead to novel therapeutic strategies.

PMID- 17556324
TI  - Pure red-cell aplasia "epidemic"--mystery completely revealed?
AB  - Starting in 1998, the number of pure red-cell aplasia (PRCA) cases in patients
      treated with recombinant human erythropoietin (rHuEPO) increased dramatically.
      Most cases were observed in patients treated with epoetin alfa produced outside
      the United States. The peak was observed in 2002; since then, the PRCA incidence
      has declined. Many factors are likely to have contributed to this up-surge. The
      molecular structure of the various epoetins and patient characteristics do not
      seem to play a major role. The route of administration holds some importance,
      because most PRCA patients received rHuEPO subcutaneously. The peak of PRCA cases
      overlapped with the removal of human serum albumin from the Eprex formulation
      (Janssen-Pharmaceutica NV, Beerse, Belgium), for which polysorbate 80 and glycine
      were substituted. Polysorbate 80 may have increased the immunogenicity of Eprex
      by eliciting the formation of epoetin-containing micelles or by interacting with
      leachates released by the uncoated rubber stoppers of prefilled syringes.
      Compared with the previous formulation, the polysorbate 80 formulation has lower
      stability, making it more susceptible to stress conditions such as insufficient
      attention to the cold chain. This situation could facilitate protein denaturation
      or aggregate formation. Uncoated rubber stoppers were replaced with coated
      stoppers, and the cold chain was reinforced; the Eprex formulation has remained
      unchanged. Even though the incidence of PRCA returned to very low levels,
      discriminating the cause-effect relationship of a single action is difficult,
      given that all occurred with a similar chronology, and that PRCA develops after a
      relatively long exposure period. Careful observation of future trends of new PRCA
      cases is thus mandatory.

PMID- 17556325
TI  - Empowerment of patients in the process of rehabilitation.
AB  - The management and appropriate treatment of peritoneal dialysis (PD) patients is
      an ongoing challenge in current health care. We believe that health education
      consisting of knowledge, skills, and self-awareness-is a useful mechanism for
      patient empowerment. Patients should have an awareness of their disease, and as
      health care providers, PD nurses have the role of focusing their patients on
      preventive care, rather than of simply training patients. An empowerment program
      is a valuable intervention for improving the self-management of patients. It can
      both improve quality of life and assist in rehabilitation.

PMID- 17556326
TI  - 30 years of peritoneal dialysis development: the past and the future.
AB  - A review is given of 30 years of development in peritoneal dialysis (PD). After a
      short description of the first 20 years, the main emphasis is put on the last 10
      years. Subjects discussed are the increasing use of PD in high-risk populations,
      peritonitis and other catheter-related problems, adequacy of dialysis and
      nutrition, patient outcomes in comparison with hemodialysis, and peritoneal
      membrane changes with time on PD. Topics that have emerged during the last decade
      and the challenges for the next decennium are discussed. The great importance of
      quality assurance in fast-growing PD populations and of prevention of long-term
      membrane alterations are emphasized.

PMID- 17556327
TI  - Peritoneal dialysis utilization and outcome: what are we facing?
AB  - Penetration of peritoneal dialysis (PD) varies tremendously across the world. It
      ranges from about 80% in Hong Kong and Mexico to just a few percentage points in
      the United States, Japan, and Germany. While PD is growing in China, India, and
      some Eastern European and South American countries, it is declining in many
      European and North American countries. In terms of outcomes, the survival of PD
      patients is generally comparable to that of hemodialysis (HD) patients and better
      than that of HD patients during the first few years on dialysis. According to the
      U.S. Renal Data System, survival of patients on PD has been improving faster than
      that of patients on HD. In terms of cost, PD is usually cheaper than HD. Hence,
      declining PD utilization is unjustified. Work is required to identify and
      overcome negative factors such as physician bias, unfair medical reimbursement
      systems, and poor patient education.

PMID- 17556328
TI  - Changing patterns of peritoneal dialysis utilization in the United States.
AB  - The proportion of incident U.S. patients with end-stage renal disease starting
      chronic peritoneal dialysis (CPD) has historically been low. The low take-on for
      CPD in the United States is likely multifactorial, but limited physician training
      and inadequate pre-dialysis patient education appear to be particularly
      important. Furthermore, two key changes have occurred in the United States: a
      steep decline in CPD take-on and a progressive increase in the use of automated
      peritoneal dialysis (APD). The decline in CPD take-on has affected virtually
      every subgroup examined and has occurred, paradoxically, when the CPD outcomes in
      the country have improved. Understanding the reasons for historically low CPD
      take-on and recent steep declines in utilization may allow for plans to reverse
      these trends to be developed.

PMID- 17556329
TI  - Development of the "peritoneal dialysis first" model in Hong Kong.
AB  - Maintenance dialysis is an expensive treatment modality for patients with end
      stage renal-disease (ESRD). The number of patients on maintenance dialysis is
      rising rapidly and will reach 2.5 million globally by 2010. The predicted
      expenditure will be US$1 trillion. Since the 1960s, Hong Kong has faced financial
      restraints on the provision of dialysis. Continuous ambulatory peritoneal
      dialysis (CAPD) and automated peritoneal dialysis at home were found to be less
      expensive than in-centre chronic hemodialysis. The development of a "peritoneal
      dialysis first" (PD-First) policy has contributed significantly to a successful
      dialysis program in Hong Kong since 1960. Currently in Hong Kong, 80% of ESRD
      patients on maintenance dialysis are on PD, mainly CAPD; 20% are on hemodialysis.
      The success of the PD-First policy is a combination of accumulated experience of
      PD in each dialysis unit that has at least 200 CAPD patients under care and of
      impressive technique and patient survival rates for this modality. Concerted
      effort by government and charity organizations and commitment on the part of
      nephrologists and nursing staff to patient education are also important in making
      the PD program in Hong Kong a successful one.

PMID- 17556330
TI  - Various obstacles to peritoneal dialysis development in Japan: too much money?
      Too much fear?
AB  - At 31 December 2005, the number of patients on maintenance dialysis in Japan was
      257,765, with 9599 patients having started dialysis that year. Kidney transplant
      cases in Japan number about 1000 annually. Thus, almost all endstage renal
      disease patients in Japan are likely to live on dialysis for the remainder of
      their lives. For various reasons, peritoneal dialysis has a lower penetration
      rate among Japanese dialysis patients, and work to educate patients and
      nephrologists about PD needs to be done.

PMID- 17556331
TI  - Increased utilization of peritoneal dialysis to cope with mounting demand for
      renal replacement therapy--perspectives from Asian countries.
AB  - With the number of end-stage renal disease (ESRD) patients growing, one of the
      crucial questions facing health care professionals and funding agencies in Asia
      is whether funding for dialysis will be sufficient to keep up with demand. During
      the ISPD's 2006 Congress, academic nephrologists and government officials from
      China, Hong Kong, India, Indonesia, Japan, Macau, Malaysia, Philippines,
      Singapore, Taiwan, Thailand, and Vietnam participated in a roundtable discussion
      on dialysis economics in Asia. The focus was policy and health care financing.
      The roundtable addressed ESRD growth in Asia and how to obtain enough funding to
      keep up with the growth in patient numbers. Various models were presented: the
      "peritoneal dialysis (PD) first" policy model, incentive programs,
      nongovernmental organizations providing PD, and PD reimbursement in a developing
      economy. This article summarizes the views of the participant nephrologists on
      how to increase the utilization of PD to improve on clinical and financial
      management of patients with ESRD.

PMID- 17556333
TI  - Mediators of inflammation and fibrosis.
AB  - During peritoneal dialysis, peritoneal cells are repeatedly exposed to a non
      physiologic hypertonic environment with high glucose content and low pH. Current
      sterile dialysis solutions cause inflammation in the submesothelial compact zone,
      leading to fibrosis, angiogenesis, and, eventually, ultrafiltration failure.
      Although the normal interstitium separates the peritoneal microvasculature from
      the dialysis fluid and makes transperitoneal transport less efficient, changes in
      the submesothelial compact zone can result in progressive increases in solute
      transfer and ultrafiltration diminution. This peritoneal dysfunction will further
      be amplified with the development of an epithelial-to-mesenchymal transition of
      mesothelial cells and dissipation of the osmotic driving force through the
      increased area and solute transport that accompany neoangiogenesis of the
      submesothelial microvasculature. The alteration of the peritoneal membrane can be
      further aggravated by peritonitis, advanced glycation end-products, and glucose
      degradation products. Furthermore, new data are emerging to support a
      proinflammatory role for peritoneal adipocytes.

PMID- 17556334
TI  - In vitro study of peritoneal fibrosis.
AB  - Peritoneal fibrosis (PF) is an important issue in peritoneal dialysis (PD)
      because it remains one of the leading causes of patient drop-out from PD. In this
      review, we focus on in vitro approaches to the pathogenesis and therapeutic
      potential of PF and on associated clinical implications. Representative Asian
      studies, initiated since mid-1990s, that have investigated matrix accumulation in
      peritoneal tissue possibly leading to PF in the PD population will be highlighted
      as examples to learn how to apply this research tool. As compared with data from
      well-designed clinical trials, observations from in vitro models may be far from
      becoming solid evidence; however, they do cast new light on options for
      investigations into therapeutic pharmaceuticals.

PMID- 17556335
TI  - Controlling inflammation in peritoneal dialysis: the role of pd-related factors
      as potential intervention targets.
AB  - Cardiovascular (CV) disease is the main cause of death in peritoneal dialysis
      (PD) patients, but the mechanisms mediating the increased CV risk observed in
      this group of patients are still largely unknown, which limits the perspective on
      effective therapeutic strategies. Patients on PD are already exposed to a number
      of traditional risk factors from the start of their chronic kidney disease (CKD),
      because many of those risk factors are common to CV disease and CKD alike. As
      renal dysfunction progresses, CKD-related risk factors are introduced, changing
      the profile of both the CV disease and the markers of risk. In this phase, which
      usually starts when glomerular filtration rate falls below 60 mL/min, the list of
      risk factors is expanded to include disturbances of mineral metabolism, anemia,
      fluid overload, uremic toxicity, and increased signs of oxidative stress and
      inflammation. Although many of the risk factors linked to CV burden are not
      related to the dialytic procedure, additional harm is introduced after the
      initiation of PD--with, for example, the presence of chronic infections and
      factors related to PD fluids, particularly reabsorption of glucose. In the
      present article, we review the impact of the novel risk factors introduced with
      the initiation of PD therapy, and we propose potential therapeutic strategies
      (which remain to be tested) for reducing CV mortality in this group of patients.

PMID- 17556336
TI  - Peritoneal fibrosis intervention.
AB  - Peritoneal fibrosis (PF) is invariably observed in patients undergoing long-term
      peritoneal dialysis (PD). The condition is thought to occur in response to a
      variety of insults, including bioincompatible dialysates (acidic solution, high
      glucose, glucose degradation products, or a combination), peritonitis, uremia,
      and chronic inflammation. Recently, the pathophysiologic mechanisms that
      contribute to the fibrosing process have been intensively studied. Transforming
      growth factor-beta has been shown to be a key mediator of PF. Loss of the
      mesothelial cell layer has been identified in several studies and shown to
      correlate with submesothelial thickening and vasculopathy. An association has
      also been identified between increased submesothelial thickness in the peritoneal
      membrane and increased solute transport, suggesting a relationship between PF and
      loss of ultrafiltration capacity. Thus, to maintain long-term PD and improve
      quality of life for patients, it is important to develop interventions for
      prevention and treatment of PF. Several strategies for peritoneal fibrosis
      intervention have been reported, including developing biocompatible dialysate,
      targeting mediators responsible for inflammation and fibrosis, and reconstituting
      the peritoneum using mesothelial or bone marrow-derived cells. Recent
      experimental trials in animal models and clinical studies are presented in this
      review.

PMID- 17556337
TI  - Studying the effects of new peritoneal dialysis solutions on the peritoneum.
AB  - BACKGROUND: Compelling data underscore the bioincompatible nature of glucose
      based peritoneal dialysis (PD) solutions and their detrimental effects on
      peritoneal physiology and morphology. New PD solutions have been formulated to
      tackle common clinical problems such as inadequate ultrafiltration or
      malnutrition, and to improve biocompatibility-the latter aimed at preserving the
      structural and functional integrity of the peritoneum and reducing adverse
      systemic effects on the patient. METHODS: This article reviews the factors in PD
      fluids that alter normal peritoneal anatomy and physiology, and the data that
      illustrate approaches to investigating the local and systemic biocompatibility of
      new PD solutions. RESULTS: Chronic exposure of the peritoneal membrane to glucose
      based PD solutions results in denudation of the mesothelium, thickened
      submesothelium, and hyalinization of the vasculature, often resulting in reduced
      or lost solute and water clearance. Data from in vitro or animal experiments and
      clinical studies have shown improved biocompatibility profiles with new PD
      solutions that are glucose-free (that is, dialysates with amino acids or
      icodextrin), bicarbonate-buffered, or compartmentalized during heat sterilization
      to reduce levels of glucose degradation products. Improved biocompatibility is
      denoted by reduced induction of proinflammatory, profibrotic, or angiogenic
      growth factors in mesothelial cells and macrophages, or by less perturbation of
      leukocyte phagocytic function. CONCLUSIONS: Data from in vitro and animal
      experiments show more favorable biocompatibility profiles with new PD fluids than
      with glucose-based dialysates. Clinical studies are ongoing to assess the impact
      of the new PD fluids on peritoneal function, morbidity, and mortality.

PMID- 17556338
TI  - Key success factors for a quality peritoneal dialysis program.
AB  - The success of a peritoneal dialysis (PD) program depends on a multitude of
      factors that are interlinked and inseparable from one another. Each program needs
      to identify its special circumstances, deficiencies, and strong points, and then
      to strategize accordingly. Ultimately, "teamwork" is the mantra for a successful
      outcome, the patient being central to all endeavors. A belief and a passion for
      PD are the fountainhead and cornerstone on which to build a quality PD program.

PMID- 17556339
TI  - Cell therapy in kidney disease: cautious optimism... but optimism nonetheless.
AB  - The recently discovered therapeutic potential of stem or progenitor cells has
      initiated development of novel treatments in a number of diseases-treatments that
      could not only improve patients' quality of life, but also halt or even prevent
      disease progression. Hypertension; fluctuations in glycemia, electrolytes,
      nutrient levels, and circulating volume; and frequent infections and the
      associated inflammation all greatly impair the endothelium in patients undergoing
      peritoneal dialysis. As our understanding of the regulatory function of the
      endothelium advances, focus is increasingly being placed on endothelial repair in
      acute and chronic renal failure and after renal transplantation. The potential of
      progenitor cells to repair damaged endothelium and to reduce inflammation in
      patients with renal failure remains unexamined; however, a successful cell
      therapy could reduce morbidity and mortality in kidney disease. Important
      contributions have been made in identifying progenitor cell populations in the
      kidney, and further investigations into the relationships of these cells with the
      pathophysiology of the disease are underway. As the kidney disease field prepares
      for the first human trials of progenitor cell therapies, we deemed it important
      to review representative original research, and to share our perspectives and
      lessons learned from clinical trials of progenitor cell-based therapies that have
      commenced in patients with cardiovascular disease.

PMID- 17556340
TI  - Dose assessment for ingestion of a 330 kilobecquerel 60Co hot particle.
AB  - On leaving the irradiated fuel bay at Pickering A nuclear power station, a worker
      triggered a whole body monitor alarm with activity in or on his head, and despite
      careful decontamination techniques he subsequently swallowed a hot particle. Over
      the next 3 d, the radioactivity was tracked through the body. It was then
      excreted in a single faecal sample and recovered for physical and radiochemical
      analysis. This analysis demonstrated that the particle contained 330 kBq of 60Co
      and only traces of other radioactivity. Its dimensions were approximately 50-130
      microm and its composition was consistent with that of Stellite 6. A dose
      assessment was carried out taking into account the residence time of the particle
      in the mouth and its transit through the body. The estimated committed effective
      dose was 1.4 mSv, and the equivalent dose to the maximally exposed 1 cm2 of skin,
      81 mSv.

PMID- 17556341
TI  - Influence of initial lung deposit on pulmonary clearance after plutonium oxide
      inhalation in rat.
AB  - Alveolar macrophages are a key element in the clearance of inhaled particles
      after phagocytosis, and thus participate actively in lung dose distribution and
      in the risk of tumour formation. We studied the influence of initial lung deposit
      (ILD) on lung clearance and distribution of activity from 3 d to 3 months after
      inhalation of two forms of PuO2 (97% 239Pu and 70% 239Pu) in rats. ILDs ranging
      from 2.1 to 17 kBq were used. The total activity measured using X-ray
      spectrometry 3 months post-inhalation, relative to the ILD, showed a similar
      decrease in all groups, with the remaining activity representing approximately
      30% of the ILD. The total activity recovered in bronchoalveolar lavages
      represented approximately 60% of the total lung activity. This ratio remained
      stable over time for the lowest ILD tested but decreased for higher ILD. In
      addition, the percentage of macrophages associated with particles decreased
      faster with time in rats with the highest ILD. Under our experimental conditions,
      there were no marked differences in lung clearance between groups. However, the
      distribution of the activity seems to vary with the time post-exposure between
      low and high ILD.

PMID- 17556342
TI  - Improvement of the measuring equipment used in the assessment of internal doses
      in emergency situations.
AB  - Emergency response plans have long been focused on accidents at nuclear power
      plants. Recently, the malevolent use of radiation aimed at creating disruption in
      the society has been considered as a possible threat. In this kind of emergency
      situations casualties will most likely be members of the public and the number of
      affected people can vary from a few to mass casualties. There is an evident need
      for rapid measurements of large groups of internally contaminated people.
      Radiation and Nuclear Safety Authority (STUK) in Finland has obtained new
      monitors for thyroid and simple whole-body measurements in field conditions as a
      part of the continuous improving of emergency preparedness. The new monitors
      consist of a NaI(Tl) detector and a control unit. The monitors work as
      spectrometers allowing real-time spectrum analysis in the field.

PMID- 17556343
TI  - The work of the CONRAD task group 5.2: research studies on biokinetic models.
AB  - The objective of this Task Group is the coordination of research studies on
      biokinetic models and the evaluation of the implications of new biokinetic models
      on dose assessment and safety standards. For this the new ICRP models, which will
      be used for a revision of ICRP Publications 30, 54, 68 and 78, are implemented
      into six different computer codes in five European countries and quality assured
      by intercomparison procedures. The work has started with the implementation of
      the new ICRP Alimentary Tract Model. New systemic models and the new NCRP wound
      model will follow. The work also includes the evaluation of experimental results
      in terms of formulation by the new model structures and a quality assurance of
      model formulation.

PMID- 17556344
TI  - Plasma clearance and urinary excretion after intravenous injection of stable 84Sr
      in humans.
AB  - Systemic kinetics and urinary excretion after intravenous injection of stable
      strontium 84Sr were evaluated in 42 investigations in human subjects. Tracer
      concentrations in plasma and urine were determined by thermal ionisation mass
      spectrometry. The initial strontium plasma clearance measured after tracer
      administration was found to be much faster than that predicted by the current
      model of the International Commission of Radiological Protection (ICRP). The
      biological half-life of the fast component plasma clearance (T(1/2)) was 0.25 h
      in comparison with 1.1 h of the ICRP value. This early clearance could be the
      consequence of a more rapid transfer from blood plasma to other compartments of
      the human body. In vitro blood tests have shown that strontium was not bound to
      red blood cells. Cumulative urinary excretion is considerably lower than the
      model prediction. The reason could be the reduced transfer rate of strontium from
      plasma to urine in the first 12 h after tracer administration. Plasma clearance
      and urinary excretion showed no dependency on the age or gender of the adult
      volunteers.

PMID- 17556345
TI  - Skeletal absorbed fractions for electrons in the adult male: considerations of a
      revised 50-microm definition of the bone endosteum.
AB  - In 1995, the International Commission on Radiological Protection (ICRP) issued
      ICRP Publication 70 which provided an extensive update to the physiological and
      anatomical reference data for the skeleton of adults and children originally
      issued in ICRP Publication 23. Although ICRP Publication 70 has been a valuable
      document in the development of reference voxel computational phantoms, additional
      guidance is needed for dose assessment in the skeletal tissues beyond that given
      in ICRP Publication 30. In this study, a computed tomography (CT) and micro-CT
      based model of the skeletal tissues is presented, which considers (1) a 50-microm
      depth in marrow for the osteoprogenitor cells, (2) electron escape from
      trabecular spongiosa to the surrounding cortical bone, (3) cortical bone to
      trabecular spongiosa cross-fire for electrons and (4) variations in specific
      absorbed fraction with changes in bone marrow cellularity for electrons. A
      representative data set is given for electron dosimetry in the craniofacial bones
      of the adult male.

PMID- 17556346
TI  - Treatment of human contamination with plutonium and americium: would orally
      administered Ca- or Zn-DTPA be effective?
AB  - Accidental or deliberate dispersion of plutonium (Pu) and americium (Am) into the
      public environment could contaminate large numbers of people by inhalation. If
      measures to reduce the internal dose are considered appropriate, oral
      administration of either calcium (Ca) or zinc (Zn) diethylenetriaminepenta-acetic
      acid (DTPA) would be the simplest treatment. Published experimental data from
      rats on the effects of oral DTPA on the retention of inhaled Pu and Am show that:
      (1) orally administered Zn-DTPA is as effective as repeated intravenous injection
      for the decorporation of Pu and Am inhaled as nitrates, although higher dosages
      are required; (2) oral Zn-DTPA appears to be an effective treatment for Am
      dioxide but not Pu dioxide; (3) maximum decorporation of Pu, by oral or
      intravenous administration, requires a large molar excess of Zn-DTPA over Pu (>1
      x 10(6)); (4) neither oral nor injected Zn-DTPA are likely to be effective for Pu
      oxides, nor when Pu and Am nitrates are mixed with other dusts. It is concluded
      that oral administration of a simple aqueous solution of Zn-DTPA could be an
      important treatment in accident or emergency scenarios after intake of pure
      chemical forms of Pu and Am, which are highly or moderately soluble in biological
      fluids. However, more research is needed on the efficacy of treatment when these
      forms are mixed with other materials. Importantly, studies designed to increase
      the efficiency of uptake of DTPA from the gastrointestinal tract could
      appreciably reduce the dosage.

PMID- 17556347
TI  - Influence of time-to-treatment, TIMI-flow grades, and ST-segment resolution on
      infarct size and infarct transmurality as assessed by delayed enhancement
      magnetic resonance imaging.
AB  - AIMS: The time-to-treatment, ST-segment resolution (STR), and TIMI-flow might be
      associated with infarct size (IS) and infarct transmurality in humans. Delayed
      enhancement magnetic resonance imaging (DE-MRI) has excellent spatial resolution
      to uncover these relations. METHODS AND RESULTS: This study analysed 135 ST
      elevation myocardial infarction (STEMI) patients randomized to prehospital
      fibrinolysis or prehospital initiated facilitated percutaneous coronary
      intervention (PCI). Reperfusion-times, 90 min STR, and TIMI-flow grades were
      assessed. IS at 6-month follow-up was determined as percentage of left
      ventricular mass (% LV). Transmurality was defined if segments exceeded > 50% DE.
      The median time-to-treatment was 93 min [interquartile range (IQR) 66.5; 158.8]
      for prehospital fibrinolysis and 85 min (IQR 60.0; 143.5) for facilitated PCI
      patients (P = 0.35). In facilitated PCI, the pre-interventional TIMI-flow
      correlated with IS [TIMI 0-1 10.8% LV (IQR 7.6; 17.3) vs. TIMI 2-3 3.9% LV (IQR
      0.9; 9.6); P = 0.002] and segments with transmurality 1.5 (IQR 0.0; 3.0) vs. 0
      (IQR 0.0; 1.5; P = 0.02). In a multivariable model, incomplete STR < 70% was the
      strongest predictor of high IS [odds ratio (OR) 6.96, P < 0.001] and
      transmurality (OR 5.71, P < 0.001) followed by time-to-treatment delay (OR/30
      min, 1.24; P = 0.01 for high IS and 1.23, P = 0.01 for transmurality).
      CONCLUSION: Time-to-treatment, STR, and TIMI-flow correlate with IS and
      transmurality underlining the assumed pathophysiological link between early flow
      restoration and perfusion in the infarct-related artery.

PMID- 17556348
TI  - Impact of multivessel disease on reperfusion success and clinical outcomes in
      patients undergoing primary percutaneous coronary intervention for acute
      myocardial infarction.
AB  - AIMS: We sought to investigate the impact of multivessel coronary artery disease
      (CAD) on reperfusion success and prognosis following primary percutaneous
      coronary intervention (PCI) in patients with acute myocardial infarction (AMI).
      The influence of multivessel disease on myocardial reperfusion and subsequent
      survival after primary PCI has not been studied. METHODS AND RESULTS: In the
      CADILLAC trial, primary PCI was performed in 2082 patients of any age with AMI
      within 12 h of symptom onset. Myocardial perfusion post-PCI assessed by ST
      segment recovery and myocardial blush and clinical outcomes were stratified by
      the extent of CAD. Single-, double-, and triple-vessel disease were present in
      1066 (51.2%), 692 (33.2%), and 324 (15.6%) patients, respectively. Patients with
      multivessel disease compared with those with single-vessel disease undergoing
      primary PCI were significantly more likely to have absent ST-segment recovery
      (13.3 vs. 7.4%, P = 0.01), though the rates of post-procedural TIMI-3 flow (89.7
      vs. 88.9%, P = 0.66) and grade 2 or 3 myocardial blush (51.2 vs. 51.5%, P = 0.91)
      in the infarct vessel were comparable. By 1 year, the cumulative incidence of
      death for patients with single-, double-, and triple-vessel disease was 3.2, 4.4,
      and 7.8%, respectively (P = 0.003), and the composite rate of major adverse
      cardiac events (MACE) was 14.8, 19.5, and 23.6%, respectively (P = 0.0006). By
      multivariable analysis, the presence of triple-vessel disease was the strongest
      predictor of 1-year death [hazard ratio (HR) = 2.60, P = 0.009], death and re
      infarction (HR = 1.88, P = 0.03), and MACE (HR = 1.80, P = 0.0009). CONCLUSION:
      Patients with extensive CAD in vessels remote from the infarct-related artery
      have reduced reperfusion success and an adverse prognosis following primary PCI
      in AMI. Future studies regarding the optimal treatment of patients with
      multivessel disease and AMI are warranted.

PMID- 17556349
TI  - Traumatic brain injury: intensive care management.
AB  - Traumatic brain injury (TBI) is a major cause of morbidity and mortality
      worldwide. The modern management of severe TBI has fallen into the domain of a
      multidisciplinary team led by neurointensivists, neuroanaesthetists, and
      neurosurgeons and is based on the avoidance of secondary injury, maintenance of
      cerebral perfusion pressure (CPP), and optimization of cerebral oxygenation. In
      this review, we will discuss the intensive care management of severe TBI with
      emphasis on the specific measures directed at the control of intracranial
      pressure and CPP.

PMID- 17556350
TI  - Impact of genetic factors on outcome from brain injury.
AB  - Most human phenotypic characteristics are determined by the interplay of
      environmental factors (whether external, or related to the internal milieu) with
      the unique genetic attributes of the individual. The same is true for
      predisposition to and outcome from most disease states, with acute brain injury
      being no exception. A greater understanding of this interplay is likely to allow
      improved risk stratification of patients, the development of new preventative and
      therapeutic modalities, and the possibility of 'individualizing' patient
      management based upon their genetic inheritance.

PMID- 17556351
TI  - Carotid endarterectomy.
AB  - Carotid endarterectomy (CEA) is performed to prevent embolic stroke in patients
      with atheromatous disease at the carotid bifurcation. There is now substantial
      evidence to support early operation in symptomatic patients, ideally within 2
      weeks of the last neurological symptoms. Thus, the anaesthetist may be faced with
      a high risk patient in whom there has been limited time for preoperative
      preparation. The operation may be performed under local or general anaesthesia.
      The advantages and disadvantages of both are explored in this review. Carotid
      shunting may offer a degree of cerebral protection, but carries its own risks and
      has not been proved to reduce morbidity and mortality. The use of carotid shunts
      is based on clinical judgement, awake neurological monitoring, and the use of
      monitors of cerebral perfusion. There is no ideal monitor of cerebral perfusion
      in the patient receiving general anaesthesia. Both the intraoperative and
      postoperative periods may be witness to dramatic haemodynamic changes that may
      compromise the cerebral or myocardial circulations. In particular, postoperative
      hypotension may compromise both myocardial and cerebral perfusion, and severe
      hypertension can cause cerebral hyperperfusion. There is as yet limited evidence
      to guide the management of these problems. In summary, CEA can yield significant
      benefit, but those with the most to gain from the operation also present the
      greatest challenge to the anaesthetist.

PMID- 17556352
TI  - Comparison of desflurane with sevoflurane for the incidence of oculocardiac
      reflex in children undergoing strabismus surgery.
AB  - BACKGROUND: The oculocardiac reflex (OCR) is frequently observed during
      strabismus surgery. This study was designed to evaluate and compare the effect of
      sevoflurane and desflurane on the incidence of OCR. METHODS: After obtaining
      Institutional Review Board approval and informed consent from parents, we
      enrolled 237 paediatric patients, aged 2-10 yr, undergoing strabismus surgery. No
      premedication was given. Anaesthesia was induced with thiopental and rocuronium.
      Patients were randomly allocated to one of the two anaesthetic regimens. Group S
      (n = 123) received sevoflurane and Group D (n = 114) received desflurane, both
      with 60% N2O/O2 for maintenance of anaesthesia. The OCR was defined as a > or =
      20% decrease in heart rate (HR) from baseline values obtained immediately before
      muscle manipulation. If the HR did not increase after release of muscle tension,
      atropine 0.01 mg kg(-1) was administered. RESULTS: There were no significant
      differences between the two groups in age, sex, body weight, and the number of
      muscles operated upon. The mean values of baseline HR were 123 (16) min(-1) in
      Group S and 121 (18) in Group D (NS). The minimum HR was 106 (22) min(-1) in
      Group S and 103 (21) in Group D (NS). There was no difference in the incidence of
      OCR between sevoflurane (26.0%) and desflurane (28.0%) anaesthesia. CONCLUSIONS:
      Both agents can be used safely during strabismus surgery in paediatric patients.

PMID- 17556353
TI  - Entecavir is a potent anti-HBV drug superior to lamivudine: experience from
      clinical trials in China.
AB  - Infection with the hepatitis B virus (HBV) can result in chronic hepatitis B
      (CHB) in many patients. Patients with CHB require regular screening and
      monitoring to facilitate disease surveillance and to determine if/when treatment
      is indicated. The current goal of CHB treatment is sustained viral suppression
      with the aim of reducing or preventing hepatic injury and disease progression.
      Effective anti-HBV therapy is now available that can suppress, but not eradicate,
      HBV replication. Among the currently licensed and approved anti-HBV
      nucleos(t)ides, entecavir demonstrates a potent anti-HBV activity and a low rate
      of emergence of drug resistance, with good safety and tolerability profiles.
      These excellent pharmacological characteristics were assessed both in large
      international clinical trials and in separate studies in China. This article
      presents results from Phase II and Phase III trials involving 876 Chinese
      patients with CHB. The results of these studies suggest that entecavir should be
      recommended as a first-line choice among the currently available anti-HBV
      nucleos(t)ides.

PMID- 17556354
TI  - Lopinavir/ritonavir monotherapy as a simplification strategy in routine clinical
      practice.
AB  - OBJECTIVES: The efficacy and safety of lopinavir/ritonavir monotherapy has been
      explored with promising results in well-controlled, randomized clinical trials.
      However, less information about its clinical usefulness in routine clinical
      practice is currently available. The objective of this study was to assess the
      effectiveness and safety of monotherapy with lopinavir/ritonavir as a treatment
      simplification strategy in HIV-infected patients with viral suppression outside a
      clinical trial setting. METHODS: Fifty-one subjects who were switched to
      lopinavir/ritonavir monotherapy and whose HIV-1 RNA was <50 copies/mL were
      included in this retrospective study. Data were obtained from a prospectively
      compiled database. The primary endpoint was the percentage of subjects who
      maintained viral suppression after 48 weeks of follow-up. Secondary endpoints
      included the incidence of adverse events and changes in CD4+ T cell count and in
      lipid profile. RESULTS: Two patients lost viral suppression, seven patients
      interrupted lopinavir/ritonavir monotherapy because of adverse events and four
      patients were lost before completing 48 weeks of follow-up. Thus, 38/40 (95.0%)
      patients maintained viral suppression when only subjects whose outcomes were
      available up to week 48 were considered and 38/51 (74.5%) patients maintained
      viral suppression when subjects who discontinued therapy or who were lost to
      follow-up were considered as treatment failures. The mean CD4+ T cell count
      significantly increased, from 541 (280) cells/mm3 at baseline to 609 (212)
      cells/mm3 at week 48 of follow-up (P=0.034). This increase was similar to that
      observed in the 48 weeks prior to lopinavir/ritonavir monotherapy (P=0.792).
      Although total cholesterol remained unchanged, there was a significant decrease
      in triglyceride levels during follow-up (P=0.029). CONCLUSIONS: Monotherapy with
      lopinavir/ritonavir is safe and effective as a treatment simplification approach
      in HIV-1-infected patients with sustained viral suppression in routine clinical
      practice, particularly in those patients already receiving a lopinavir/ritonavir
      based antiretroviral regimen.

PMID- 17556355
TI  - Emergence and maintenance of resistance to fluoroquinolones and coumarins in
      Staphylococcus aureus: predictions from in vitro studies.
AB  - OBJECTIVES: Fluoroquinolones and coumarins interfere with the activity of
      bacterial type II topoisomerase enzymes. We examined the development of
      resistance to these agents in Staphylococcus aureus and determined the effect of
      simultaneous topoisomerase IV and DNA gyrase mutations on the biological fitness
      of the organism. This work aimed to gain insight into how such mutants might
      arise and survive in the clinical environment. METHODS: Spontaneous mutants
      resistant to fluoroquinolones and coumarins were selected in S. aureus.
      Resistance mutations were identified by DNA sequencing of PCR amplicons
      corresponding to the genes encoding topoisomerase IV and DNA gyrase. In vitro
      fitness of resistant mutants was compared with the antibiotic-susceptible
      progenitor strain using pair-wise competition assays. RESULTS: Mutants
      simultaneously resistant to both a fluoroquinolone and either of the coumarins,
      novobiocin or coumermycin A1, could not be recovered following a single-step
      selection. However, mutants concurrently resistant to both classes of
      antimicrobial could be generated by step-wise selections. These mutants
      demonstrated reductions in competitive fitness of up to 36%. CONCLUSIONS: Dual
      targeting of topoisomerase IV and DNA gyrase enzymes, for example with the
      combination of a fluoroquinolone and a coumarin agent, could minimize the
      emergence of resistance to these drugs in S. aureus. However, resistance
      associated fitness costs may not be sufficient to limit the survival of mutants
      with dual resistance, if they arose in the clinical setting.

PMID- 17556356
TI  - Crystal structure of human estrogen-related receptor alpha in complex with a
      synthetic inverse agonist reveals its novel molecular mechanism.
AB  - Inverse agonists of the constitutively active human estrogen-related receptor
      alpha (ERRalpha, NR3B1) are of potential interest for several disease indications
      (e.g. breast cancer, metabolic diseases, or osteoporosis). ERRalpha is
      constitutively active, because its ligand binding pocket (LBP) is practically
      filled with side chains (in particular with Phe(328), which is replaced by Ala in
      ERRbeta and ERRgamma). We present here the crystal structure of the ligand
      binding domain of ERRalpha (containing the mutation C325S) in complex with the
      inverse agonist cyclohexylmethyl-(1-p-tolyl-1H-indol-3-ylmethyl)-amine (compound
      1a), to a resolution of 2.3A(.) The structure reveals the dramatic multiple
      conformational changes in the LBP, which create the necessary space for the
      ligand. As a consequence of the new side chain conformation of Phe(328) (on helix
      H3), Phe(510)(H12) has to move away, and thus the activation helix H12 is
      displaced from its agonist position. This is a novel mechanism of H12
      inactivation, different from ERRgamma, estrogen receptor (ER) alpha, and ERbeta.
      H12 binds (with a surprising binding mode) in the coactivator groove of its
      ligand binding domain, at a similar place as a coactivator peptide. This is in
      contrast to ERRgamma but resembles the situation for ERalpha (raloxifene or 4
      hydroxytamoxifen complexes). Our results explain the novel molecular mechanism of
      an inverse agonist for ERRalpha and provide the basis for rational drug design to
      obtain isotype-specific inverse agonists of this potential new drug target.
      Despite a practically filled LBP, the finding that a suitable ligand can induce
      an opening of the cavity also has broad implications for other orphan nuclear
      hormone receptors (e.g. the NGFI-B subfamily).

PMID- 17556357
TI  - RB loss promotes aberrant ploidy by deregulating levels and activity of DNA
      replication factors.
AB  - The retinoblastoma tumor suppressor (RB) is functionally inactivated in many
      human cancers. Classically, RB functions to repress E2F-mediated transcription
      and inhibit cell cycle progression. Consequently, RB ablation leads to loss of
      cell cycle control and aberrant expression of E2F target genes. Emerging evidence
      indicates a role for RB in maintenance of genomic stability. Here, mouse adult
      fibroblasts were utilized to demonstrate that aberrant DNA content in RB
      deficient cells occurs concomitantly with an increase in levels and chromatin
      association of DNA replication factors. Furthermore, following exposure to
      nocodazole, RB-proficient cells arrest with 4 n DNA content, whereas RB-deficient
      cells bypass the mitotic block, continue DNA synthesis, and accumulate cells with
      higher ploidy and micronuclei. Under this condition, RB-deficient cells also
      retain high levels of tethered replication factors, MCM7 and PCNA, indicating
      that DNA replication occurs in these cells under nonpermissive conditions.
      Exogenous expression of replication factors Cdc6 or Cdt1 in RB-proficient cells
      does not recapitulate the RB-deficient cell phenotype. However, ectopic E2F
      expression in RB-proficient cells elevated ploidy and bypassed the response to
      nocodazole-induced cessation of DNA replication in a manner analogous to RB loss.
      Collectively, these results demonstrate that deregulated S phase control is a key
      mechanism by which RB-deficient cells acquire elevated ploidy.

PMID- 17556358
TI  - Phenotypic and structural analyses of hepatitis C virus NS3 protease Arg155
      variants: sensitivity to telaprevir (VX-950) and interferon alpha.
AB  - Telaprevir (VX-950) is a highly selective, potent inhibitor of the hepatitis C
      virus (HCV) NS3.4A serine protease. It has demonstrated strong antiviral activity
      in patients chronically infected with genotype 1 HCV when dosed alone or in
      combination with peginterferon alfa-2a. Substitutions of Arg(155) of the HCV NS3
      protease domain have been previously detected in HCV isolates from some patients
      during telaprevir dosing. In this study, Arg(155) was replaced with various
      residues in genotype 1a protease domain proteins and in genotype 1b HCV
      subgenomic replicons. Characterization of both the purified enzymes and
      reconstituted replicon cells demonstrated that substitutions of Arg(155) with
      these residues conferred low level resistance to telaprevir (<25-fold). An x-ray
      structure of genotype 1a HCV protease domain with the R155K mutation, in a
      complex with an NS4A co-factor peptide, was determined at a resolution of 2.5A.
      The crystal structure of the R155K protease is essentially identical to that of
      the wild-type apoenzyme (Protein Data Bank code 1A1R) except for the side chain
      of mutated residue 155. Telaprevir was docked into the x-ray structure of the
      R155K protease, and modeling analysis suggests that the P2 group of telaprevir
      loses several hydrophobic contacts with the Lys(155) side chain. It was
      demonstrated that replicon cells containing substitutions at NS3 protease residue
      155 remain fully sensitive to interferon alpha or ribavirin. Finally, these
      variant replicons were shown to have reduced replication capacity compared with
      the wild-type HCV replicon in cells.

PMID- 17556359
TI  - The early growth response factor-1 is involved in stem cell factor (SCF)-induced
      interleukin 13 production by mast cells, but is dispensable for SCF-dependent
      mast cell growth.
AB  - The stem cell factor (SCF) plays a central role in the regulation of mast cell
      function and growth. However, roles of transcription factors involved in these
      processes remain incompletely defined. The early growth response factor-1 (Egr-1)
      is a member of the zinc finger transcription factor family. A role for Egr-1 in
      SCF-induced mast cell activation and growth was investigated in mouse bone marrow
      derived mast cells (BMMC). The stimulation of BMMC with SCF induced a strong
      expression of Egr-1 mRNA. SCF-induced Egr-1 nuclear translocation and DNA binding
      were demonstrated by electrophoretic mobility shift assay (EMSA) and
      immunofluorescence assay. SCF-induced IL-13 expression was significantly reduced
      at both mRNA and protein levels in Egr-1-deficient BMMC. In addition, the synergy
      between IgE and SCF on IL-13 and IL-4 production was reduced in Egr-1-deficient
      mast cells. Interestingly, Egr-1 deficiency had little effect on SCF-induced mast
      cell growth. SCF-induced Egr activation likely requires tyrosine phosphorylation
      because a tyrosine kinase inhibitor PP2 blocked SCF-induced nuclear protein
      binding to Egr probe as determined by EMSA. Thus, Egr-1 is required for SCF
      induced IL-13 expression, but not mast cell growth. Egr-1 represents a novel
      mechanism for SCF-induced mast cell activation.

PMID- 17556360
TI  - Control of Bax homodimerization by its carboxyl terminus.
AB  - The regulated oligomerization of proteins is increasingly understood to be an
      important step in many cellular processes, including signaling, transcription,
      and protein degradation. The activity of Bax, which is essential for the
      completion of apoptosis, has been shown to be associated with its
      oligomerization: homodimerization that appears to facilitate mitochondrial
      permeabilization during apoptosis and heterodimerization with multidomain anti
      apoptotic members of the Bcl-2 family inhibiting this process. Several domains
      have been identified to be crucial in the homo-/heterodimerization or
      oligomerization of Bax, especially the so-called Bax homology 3 domain. In this
      study we show that although the carboxyl terminus of Bax is not implicated in its
      mitochondrial localization, it has a role in the dimerization process and thus in
      its activity.

PMID- 17556361
TI  - {gamma}-Secretase Substrate Concentration Modulates the Abeta42/Abeta40 Ratio:
      IMPLICATIONS FOR ALZHEIMER DISEASE.
AB  - Mutation of the amyloid precursor protein (APP), presenilin-1, or presenilin-2
      results in the development of early onset autosomal dominant forms of Alzheimer
      disease (AD). These mutations lead to an increased Abeta42/Abeta40 ratio that
      correlates with the onset of disease. However, it remains unknown how these
      mutations affect gamma-secretase, a protease that generates the termini of
      Abeta40 and Abeta42. Here we have determined the reaction mechanism of gamma
      secretase with wild type and three mutated APP substrates. Our findings indicate
      that despite the overall outcome of an increased Abeta42/Abeta40 ratio, these
      mutations each display rather distinct reactivity to gamma-secretase.
      Intriguingly, we found that the ratio of Abeta42/Abeta40 is variable with
      substrate concentration; increased substrate concentrations result in higher
      ratios of Abeta42/Abeta40. Moreover, we demonstrated that reduction of gamma
      secretase substrate concentration by BACE1 inhibition in cells decreased the
      Abeta42/Abeta40 ratio. This study indicates that biological factors affecting
      targets such as BACE1 and APP, which ultimately cause an increased concentration
      of gamma-secretase substrate, can augment the Abeta42/Abeta40 ratio and may play
      a causative role in sporadic AD. Therefore, strategies lowering the
      Abeta42/Abeta40 ratio through partial reduction of gamma-secretase substrate
      production may introduce a practical therapeutic modality for treatment of AD.

PMID- 17556362
TI  - Genetic evidence for a protective role for heat shock factor 1 and heat shock
      protein 70 against colitis.
AB  - Inflammatory bowel disease (IBD) involves infiltration of leukocytes into
      intestinal tissue, resulting in intestinal damage induced by reactive oxygen
      species (ROS). Pro-inflammatory cytokines and cell adhesion molecules (CAMs) play
      important roles in this infiltration of leukocytes. The roles of heat shock
      factor 1 (HSF1) and heat shock proteins (HSPs) in the development of IBD are
      unclear. In this study, we examined the roles of HSF1 and HSPs in an animal model
      of IBD, dextran sulfate sodium (DSS)-induced colitis. The colitis worsened or was
      ameliorated in HSF1-null mice or transgenic mice expressing HSP70 (or HSF1),
      respectively. Administration of DSS up-regulated the expression of HSP70 in
      colonic tissues in an HSF1-dependent manner. Expression of pro-inflammatory
      cytokines and CAMs and the level of cell death observed in colonic tissues were
      increased or decreased in DSS-treated HSF1-null mice or transgenic mice
      expressing HSP70, respectively, relative to control wild-type mice. Relative to
      macrophages from control wild-type mice, macrophages prepared from HSF1-null mice
      or transgenic mice expressing HSP70 displayed enhanced or reduced activity,
      respectively, for the generation of pro-inflammatory cytokines in response to
      lipopolysaccharide stimulation. Suppression of HSF1 or HSP70 expression in vitro
      stimulated lipopolysaccharide-induced up-regulation of CAMs or ROS-induced cell
      death, respectively. This study provides the first genetic evidence that HSF1 and
      HSP70 play a role in protecting against DSS-induced colitis. Furthermore, this
      protective role seems to involve various mechanisms, such as suppression of
      expression of pro-inflammatory cytokines and CAMs and ROS-induced cell death.

PMID- 17556363
TI  - High circulating leptin receptors with normal leptin sensitivity in liver
      specific insulin receptor knock-out (LIRKO) mice.
AB  - Liver-specific insulin receptor knock-out (LIRKO) mice display hyperinsulinemia,
      abnormal glucose metabolism, and progressive liver dysfunction. In addition,
      circulating leptin levels appear to be increased more than 10-fold. However, food
      intake, body weight, and adipose mass are not significantly altered in LIRKO mice
      compared with wild-type littermates. Using a ligand immunofunctional assay, we
      found that the apparent increase in circulating leptin in LIRKO mice is because
      of an 80-fold increased serum level of soluble leptin receptor. Gene expression
      analysis by microarray and real time PCR reveals the liver as the source of
      soluble leptin receptor in LIRKO mice, with an increase in expression of the
      short (Ob-Ra), long (Ob-Rb), and soluble (Ob-Re) forms of the leptin receptor.
      Direct control of leptin receptor expression by insulin could also be
      demonstrated in isolated hepatocytes from normal mice. Despite the markedly
      increased levels of leptin receptor in their circulation, LIRKO mice exhibit
      normal or even enhanced leptin sensitivity, as assessed by their physiological
      and molecular responses to exogenous leptin administration and their lower base
      line hypothalamic levels of SOCS3 mRNA. Thus, insulin signaling in the liver
      plays an important role in control of leptin receptor expression and shedding. In
      the LIRKO mouse, this is lost, leading to markedly increased leptin receptors
      into the circulation. These high levels of circulating leptin receptor bind
      leptin and likely alter its clearance, but do not inhibit leptin action and may
      actually potentiate leptin action. In this manner, insulin signaling in liver
      plays an important role in leptin homeostasis and fine modulation of leptin
      action.

PMID- 17556364
TI  - Differentiation of human circulating fibrocytes as mediated by transforming
      growth factor-beta and peroxisome proliferator-activated receptor gamma.
AB  - Fibrocytes are a distinct population of fibroblast-like progenitor cells in
      peripheral blood that have recently been shown to possess plasticity to
      differentiate along mesenchymal lineages, including commitment to myofibroblast
      and adipocyte cells. Here, we demonstrated that transforming growth factor (TGF)
      beta1 drives fibrocyte-to-myofibroblast differentiation through activating
      Smad2/3 and SAPK/JNK MAPK pathways, which in turn stimulates alpha-smooth muscle
      actin expression. We determined that SAPK/JNK signaling acts in a positive
      feedback loop to modulate Smad2/3 nuclear availability and Smad2/3-dependent
      transcription. Conversely, fibrocyte-to-adipocyte differentiation is driven by
      the peroxisome proliferator-activated receptor (PPAR) gamma agonist troglitazone,
      which is associated with cytoplasmic lipid accumulation and induction of aP2.
      Treatment with troglitazone also disrupted TGF beta 1-activated SAPK/JNK
      signaling, leading to decreased Smad2/3 transactivation activity and alpha-smooth
      muscle actin expression. Interestingly, TGF beta 1 was demonstrated to have
      reciprocal inhibition on fibrocyte differentiation to adipocytes. By activating
      SAPK/JNK signaling, which is normally suppressed during adipogenesis, PPARgamma
      dependent transactivation activity and induction of aP2 expression were
      disrupted. Taken together, within the context of the local microenvironmental
      niche, the delicate balance of PPARgamma and TGF beta 1 activation drives the
      selection of an adipocyte or myofibroblast differentiation pathway through
      SAPK/JNK signaling.

PMID- 17556365
TI  - Characterizing early events associated with the activation of target genes by
      1,25-dihydroxyvitamin D3 in mouse kidney and intestine in vivo.
AB  - In this report, we explore the interaction of the vitamin D receptor (VDR) at
      regulatory sites within both the Cyp24a1 and the Trpv6 genes using chromatin
      immunoprecipitation techniques in a mouse model in vivo. We show that exogenous
      1,25(OH)(2)D(3) induces rapid VDR and RXR (retinoid X receptor) binding to the
      Cyp24a1 gene in both the kidney and the intestine and to the Trpv6 gene in the
      intestine. Separate studies of Trpv6 in vitro suggest that VDR binding occurs
      directly to VDR response elements located -2 and -4 kb upstream of the TSS. VDR
      binding is dose-dependent, demonstrating EC(50) values that are comparable with
      those for the induction of both Cyp24a1 and Trpv6 mRNA. Importantly, interaction
      of the VDR with these targets results in rapid changes in histone 4 acetylation
      as well as the recruitment of RNA polymerase II. The presence of both VDR and RNA
      polymerase II at these sites declines between 3-6 h, whereas the changes observed
      in acetylation decrease more slowly. Finally, we show that whereas mediator
      protein 1 is recruited to the Cyp24a1 promoter in the intestine, this coactivator
      is apparently not required for Trpv6 activation. These studies provide the first
      evidence for 1,25(OH)(2)D(3)-induced VDR interaction at key target genes in vivo,
      revealing the consequences of that interaction on the Cyp24a1 and Trpv6 genes.

PMID- 17556366
TI  - Differential association of hemoglobin with proinflammatory high density
      lipoproteins in atherogenic/hyperlipidemic mice. A novel biomarker of
      atherosclerosis.
AB  - Studies in both mice and humans suggest that the anti- or proinflammatory nature
      of high density lipoprotein (HDL) may be a more sensitive predictor of risk for
      coronary heart disease events. In this study, we report the identification and
      characterization of two proteins (m/z 14,900 and 15,600) that are most
      dramatically associated with HDL in mouse models of atherosclerosis. Mass
      spectral analyses of proinflammatory HDL identified the two peaks to be
      hemoglobin (Hb) alpha and beta chains, respectively, with no apparent post
      translational modification. Biochemical analysis confirmed the differential
      association of Hb with HDL from hyperlipidemic mice. We further show that HDL
      associated Hb is predominantly in the oxyHb form with distinct physical and
      chemical properties. Furthermore oxyHb-containing proinflammatory HDL potently
      consumed nitric oxide and contracted arterial vessels ex vivo. Moreover Hb also
      was found differentially associated with HDL from coronary heart disease patients
      compared with healthy controls. Our data suggest that Hb contributes to the
      proinflammatory nature of HDL in mouse and human models of atherosclerosis and
      may serve as a novel biomarker for atherosclerosis.

PMID- 17556367
TI  - Characterization of the properties and trafficking of an anchorless form of the
      prion protein.
AB  - Conversion of PrP(C) into PrP(Sc) is the central event in the pathogenesis of
      transmissible prion diseases. Although the molecular basis of this event and the
      intracellular compartment where it occurs are not yet understood, the association
      of PrP with cellular membranes and in particular its presence in detergent
      resistant microdomains appears to be of critical importance. In addition it
      appears that scrapie conversion requires membrane-bound
      glycosylphosphatidylinositol (GPI)-linked PrP. The GPI anchor may affect either
      the conformation, the intracellular localization, or the association of the prion
      protein with specific membrane domains. However, how this occurs is not known. To
      understand the relevance of the GPI anchor for the cellular behavior of PrP, we
      have studied the biosynthesis and localization of a PrP version which lacks the
      GPI anchor attachment signal (PrP Delta GPI). We found that PrP Delta GPI is
      tethered to cell membranes and associates to membrane detergent-resistant
      microdomains but does not assume a transmembrane topology. Differently to PrP(C),
      this protein does not localize at the cell surface but is mainly released in the
      culture media in a fully glycosylated soluble form. The cellular behavior of
      anchorless PrP explains why PrP Delta GPI Tg mice can be infected but do not show
      the classical signs of the disorder, thus indicating that the plasma membrane
      localization of PrP(C) and/or of the converted scrapie form might be necessary
      for the development of a symptomatic disease.

PMID- 17556368
TI  - The Birt-Hogg-Dube and tuberous sclerosis complex homologs have opposing roles in
      amino acid homeostasis in Schizosaccharomyces pombe.
AB  - Birt-Hogg-Dube (BHD) is a tumor suppressor gene disorder characterized by skin
      hamartomas, cystic lung disease, and renal cell carcinoma. The fact that
      hamartomas, lung cysts, and renal cell carcinoma can also occur in tuberous
      sclerosis complex (TSC) suggests that the BHD and TSC proteins may function
      within a common pathway. To evaluate this hypothesis, we deleted the BHD homolog
      in Schizosaccharomyces pombe. Expression profiling revealed that six permease and
      transporter genes, known to be down-regulated in Deltatsc1 and Deltatsc2, were up
      regulated in Deltabhd, and levels of specific intracellular amino acids known to
      be low in Deltatsc1 and Deltatsc2 were elevated in Deltabhd. This "opposite"
      profile was unexpected, given the overlapping clinical phenotypes. The TSC1/2
      proteins inhibit Rheb in mammals, and Tsc1/Tsc2 inhibit Rhb1 in S. pombe.
      Expression of a hypomorphic allele of rhb1(+) dramatically increased permease
      expression levels in Deltabhd but not in wild-type yeast. Loss of Bhd sensitized
      yeast to rapamycin-induced increases in permease expression levels, and rapamycin
      induced lethality in Deltabhd yeast expressing the hypomorphic Rhb1 allele. In S.
      pombe, it is known that Rhb1 binds Tor2, and Tor2 inhibition leads to up
      regulation of permeases including those that are regulated by Bhd. Our data,
      therefore, suggest that Bhd activates Tor2. If the mammalian BHD protein,
      folliculin, similarly activates mammalian target of rapamycin, it will be of
      great interest to determine how mammalian target of rapamycin inhibition in BHD
      patients and mammalian target of rapamycin activation in TSC patients lead to
      overlapping clinical phenotypes.

PMID- 17556369
TI  - The CB1 cannabinoid receptor mediates excitotoxicity-induced neural progenitor
      proliferation and neurogenesis.
AB  - Endocannabinoids are lipid signaling mediators that exert an important
      neuromodulatory role and confer neuroprotection in several types of brain injury.
      Excitotoxicity and stroke can induce neural progenitor (NP) proliferation and
      differentiation as an attempt of neuroregeneration after damage. Here we
      investigated the mechanism of hippocampal progenitor cell engagement upon
      excitotoxicity induced by kainic acid administration and the putative involvement
      of the CB1 cannabinoid receptor in this process. Adult NPs express kainate
      receptors that mediate proliferation and neurosphere generation in vitro via CB1
      cannabinoid receptors. Similarly, in vivo studies showed that excitotoxicity
      induced hippocampal NPs proliferation and neurogenesis are abrogated in CB1
      deficient mice and in wild-type mice administered with the selective CB1
      antagonist rimonabant (N-piperidino-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4
      methyl-3-pyrazolecarboxamide; SR141716). Kainate stimulation increased basic
      fibroblast growth factor (bFGF) expression in cultured NPs in a CB1-dependent
      manner as this response was prevented by rimonabant and mimicked by
      endocannabinoids. Likewise, in vivo analyses showed that increased hippocampal
      expression of bFGF, as well as of brain-derived neurotrophic factor and epidermal
      growth factor, occurs upon excitotoxicity and that CB1 receptor ablation prevents
      this induction. Moreover, excitotoxicity increased the number of CB1+ bFGF+
      cells, and this up-regulation preceded NP proliferation. In summary, our results
      show the involvement of the CB1 cannabinoid receptor in NP proliferation and
      neurogenesis induced by excitotoxic injury and support a role for bFGF signaling
      in this process.

PMID- 17556370
TI  - Female gender-specific inhibition of KCNQ1 channels and chloride secretion by
      17beta-estradiol in rat distal colonic crypts.
AB  - The estrogen sex steroid 17beta-estradiol rapidly inhibits secretagogue
      stimulated cAMP-dependent Cl(-) secretion in the female rat distal colonic crypt
      by the inhibition of basolateral K(+) channels. In Ussing chamber studies, both
      the anti-secretory response and inhibition of basolateral K(+) current was shown
      to be attenuated by pretreatment with rottlerin, a PKCdelta-specific inhibitor.
      In whole cell patch-clamp analysis, 17beta-estradiol inhibited a chromanol 293B
      sensitive KCNQ1 channel current in isolated female rat distal colonic crypts.
      Estrogen had no effect on KCNQ1 channel currents in colonic crypts isolated from
      male rats. Female distal colonic crypts expressed a significantly higher amount
      of PKCdelta in comparison to male tissue. PKCdelta and PKA were activated at 5
      min in response to 17beta-estradiol in female distal colonic crypts only. Both
      PKCdelta- and PKA-associated with the KCNQ1 channel in response to 17beta
      estradiol in female distal colonic crypts, and no associations were observed in
      crypts from males. PKA activation, association with KCNQ1, and phosphorylation of
      the channel were regulated by PKCdelta as the responses were blocked by
      pretreatment with rottlerin. Taken together, our experiments have identified the
      molecular targets underlying the anti-secretory response to estrogen involving
      the inhibition of KCNQ1 channel activity via PKCdelta- and PKA-dependent
      signaling pathways. This is a novel gender-specific mechanism of regulation of an
      ion channel by estrogen. The anti-secretory response described in this study
      provides molecular insights whereby estrogen causes fluid retention effects in
      the female during periods of high circulating plasma estrogen levels.

PMID- 17556371
TI  - Core protein machinery for mammalian phosphatidylinositol 3,5-bisphosphate
      synthesis and turnover that regulates the progression of endosomal transport.
      Novel Sac phosphatase joins the ArPIKfyve-PIKfyve complex.
AB  - Perturbations in phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2)
      synthesizing enzymes result in enlarged endocytic organelles from yeast to
      humans, indicating evolutionarily conserved function of PtdIns(3,5)P2 in endosome
      related events. This is reinforced by the structural and functional homology of
      yeast Vac14 and human Vac14 (ArPIKfyve), which activate yeast and mammalian
      PtdIns(3,5)P2-producing enzymes, Fab1 and PIKfyve, respectively. In yeast,
      PtdIns(3,5)P2-specific phosphatase, Fig4, in association with Vac14, turns over
      PtdIns(3,5)P2, but whether such a mechanism operates in mammalian cells and what
      the identity of mammalian Fig4 may be are unknown. Here we have identified and
      characterized Sac3, a Sac domain phosphatase, as the Fig4 mammalian counterpart.
      Endogenous Sac3, a widespread 97-kDa protein, formed a stable ternary complex
      with ArPIKfyve and PIKfyve. Concordantly, Sac3 cofractionated and colocalized
      with ArPIKfyve and PIKfyve. The intrinsic Sac3(WT) phosphatase activity
      preferably hydrolyzed PtdIns(3,5)P2 in vitro, although the other D5
      phosphorylated polyphosphoinositides were also substrates. Ablation of endogenous
      Sac3 by short interfering RNAs elevated PtdIns(3,5)P2 in (32)P-labeled HEK293
      cells. Ectopically expressed Sac3(WT) in COS cells colocalized with and dilated
      EEA1-positive endosomes, consistent with the PtdIns(3,5)P2 requirement in early
      endosome dynamics. In vitro reconstitution of carrier vesicle formation from
      donor early endosomes revealed a gain of function upon Sac3 loss, whereas PIKfyve
      or ArPIKfyve protein depletion produced a loss of function. These data
      demonstrate a coupling between the machinery for PtdIns(3,5)P2 synthesis and
      turnover achieved through a physical assembly of PIKfyve, ArPIKfyve, and Sac3. We
      suggest that the tight regulation in PtdIns(3,5)P2 homeostasis is mechanistically
      linked to early endosome dynamics in the course of cargo transport.

PMID- 17556373
TI  - Differential expression of alternatively spliced mRNAs of Arabidopsis SR protein
      homologs, atSR30 and atSR45a, in response to environmental stress.
AB  - Serine/arginine-rich (SR) proteins are associated with either the regulation or
      the execution of both constitutive splicing and the selection of alternative
      splice sites in animals and plants. We demonstrated the molecular
      characterization of a homolog of SR protein, atSR45a, in Arabidopsis plants. Six
      types of mRNA variants (atSR45a-1a-e and atSR45a-2) were generated by the
      alternative selection of transcriptional initiation sites and the alternative
      splicing of introns in atSR45a pre-mRNA. The atSR45a-1a and -2 proteins, presumed
      mature forms, were located in the nucleus and interacted with U1-70K, suggesting
      that these proteins function as a splicing factor in Arabidopsis. The levels of
      the transcripts atSR45a and atSR30, SF2/ASF-like SR proteins, were increased by
      various types of stress, such as high-light irradiation and salinity.
      Furthermore, the splicing patterns of atSR45a and atSR30 pre-mRNA themselves were
      altered under these stressful conditions. In particular, the expression of
      atSR45a-1a, atSR45a-2, atSR30 mRNA1 and atSR30 mRNA3 was greatly increased by
      high-light irradiation. These results indicate that the regulation of
      transcription and alternative splicing of atSR45a and atSR30 is responsive to
      various stressful conditions.

PMID- 17556375
TI  - IMA the role of oxidative stress.

PMID- 17556372
TI  - Rodent A beta modulates the solubility and distribution of amyloid deposits in
      transgenic mice.
AB  - The amino acid sequence of amyloid precursor protein (APP) is highly conserved,
      and age-related A beta aggregates have been described in a variety of vertebrate
      animals, with the notable exception of mice and rats. Three amino acid
      substitutions distinguish mouse and human A beta that might contribute to their
      differing properties in vivo. To examine the amyloidogenic potential of mouse A
      beta, we studied several lines of transgenic mice overexpressing wild-type mouse
      amyloid precursor protein (moAPP) either alone or in conjunction with mutant PS1
      (PS1dE9). Neither overexpression of moAPP alone nor co-expression with PS1dE9
      caused mice to develop Alzheimer-type amyloid pathology by 24 months of age. We
      further tested whether mouse A beta could accelerate the deposition of human A
      beta by crossing the moAPP transgenic mice to a bigenic line expressing human
      APPswe with PS1dE9. The triple transgenic animals (moAPP x APPswe/PS1dE9)
      produced 20% more A beta but formed amyloid deposits no faster and to no greater
      extent than APPswe/PS1dE9 siblings. Instead, the additional mouse A beta
      increased the detergent solubility of accumulated amyloid and exacerbated amyloid
      deposition in the vasculature. These findings suggest that, although mouse A beta
      does not influence the rate of amyloid formation, the incorporation of A beta
      peptides with differing sequences alters the solubility and localization of the
      resulting aggregates.

PMID- 17556376
TI  - Incidence and predictors of in-hospital events after first implantation of
      pacemakers.
AB  - AIMS: Despite an annual rise in the numbers of patients receiving their first
      pacemaker (PM), the risks of the implantation procedure remains unclear. The
      purpose of this prospective study is to estimate the incidence of in-hospital
      events after first PM implantation and to determine the predictors of these
      events. METHODS AND RESULTS: Patients with conventional pacing diagnosis were
      included in the Dutch multicentre FOLLOWPACE PM registry that prospectively
      documented patients' prognosis and quality of life, and PM events after first
      implantation. From these registry characteristics, implantation data and in
      hospital findings were analysed as potential predictors for events in a sample of
      1198 patients. In 111 patients studied, at least one serious in-hospital event
      occurred (incidence 10.1%, 95%CI: 8.9-12.3). Six variables, i.e. a lower body
      mass index, presence of heart failure in medical history, main indication for
      implantation, vena subclavia use for venous access, active atrial lead fixation,
      and the implantation of a dual chamber system, were found to be independent
      predictors of events after first PM implantation. The overall multivariable model
      yielded an ROC area of 0.65 (95%CI: 0.60-0.70). CONCLUSION: This large
      prospective multicentre study identified six variables as independent predictors
      for serious in-hospital events after first implantation. This may assist the
      implanting cardiologist and surgeon to identify patients at higher risk, during
      and immediately after PM implantation.

PMID- 17556377
TI  - IGF-II regulates metastatic properties of choriocarcinoma cells through the
      activation of the insulin receptor.
AB  - Choriocarcinoma is a highly malignant tumor that can arise from trophoblasts of
      any type of gestational event but most often from complete hydatidiform mole. IGF
      II plays a fundamental role in placental development and may play a role in
      gestational trophoblastic diseases. Several studies have shown that IGF-II is
      expressed at high levels in hydatidiform moles and choriocarcinoma tissues;
      however, conflicting data exist on how IGF-II regulates the behaviour of
      choriocarcinoma cells. The purpose of this study was to determine the
      contribution of the receptors for IGF-I and insulin to the actions of IGF-II on
      the regulation of choriocarcinoma cells metastasis. An Immuno Radio Metric Assay
      was used to analyse the circulating and tissue levels of IGF-I and IGF-II in 24
      cases of hydatidiform mole, two cases of choriocarcinoma and eight cases of
      spontaneous abortion at the same gestational age. The JEG-3 choriocarcinoma cell
      line was used to investigate the role of IGF-II in the regulation of cell
      invasion. We found that mole and choriocarcinoma tissue express high levels of
      IGF-II compared to first trimester placenta. Both IGF-I and IGF-II regulate
      choriocarcinoma cell invasion in a dose dependent manner but through a different
      mechanism. IGF-II effects involve the activation of the InsR while IGF-I uses the
      IGF-IR. The positive effects of IGF-II on invasion are the result of enhanced
      cell adhesion and chemotaxis (specifically towards collagen IV). The actions of
      IGF-II but not those of IGF-I were sensitive to inhibition by the insulin
      receptor inhibitor HNMPA(AM)3. Our results demonstrate that the insulin receptor
      regulates choriocarcinoma cell invasion.

PMID- 17556378
TI  - Estrogen receptor alpha polymorphisms and fertility in populations with different
      reproductive patterns.
AB  - The estrogen receptor (ER) plays an important role in mediating estrogen action
      on target tissues. ER-alpha, the most abundant, is found in all human
      reproductive tissues and studies on alpha-ER knockout mice have highlighted its
      role in reproduction. ER-alpha gene (ESR1) polymorphisms have been associated
      with a variety of disorders including human infertility. In this study, we
      examined the association of ESR1 PvuII and XbaI polymorphisms with fertility in
      two populations with different reproductive patterns and precisely in a sample of
      healthy Italian men and women (n=178) and in a sample of healthy African
      Ecuadorian women (n=57). ESR1 xx and ppxx genotypes among the Italian men were
      found to be associated with an above-median number of children (P=0.01 and
      P=0.004, respectively). ESR1 pp genotype among the Italian women showed a
      tendency to be associated with a lower number of abortions (P=0.04), whereas ESR1
      pp and ppxx genotypes among African-Ecuadorian women were associated with a
      higher number of children (P=0.02 and P=0.03, respectively). These results are
      consistent with previous observations indicating a role of ESR1 genotypes in
      human infertility and give insight into the complex interactions between
      genotypes and reproductive behaviours in human populations.

PMID- 17556379
TI  - Parity for whom? Exemptions and the extent of state mental health parity
      legislation.
AB  - Between 1997 and 2003, the share of workers subject to mental health parity laws
      greatly increased. But because of exemptions for self-insured firms and small
      firms, coverage is much lower than a simple tally of state mandates would
      suggest. Limits on the types of conditions covered further weaken these laws.
      This paper summarizes the extent and scope of state parity legislation in terms
      of the number of insured private-sector employees covered. It explicitly accounts
      for the Employee Retirement Income Security Act (ERISA) exemption for self
      insured plans, exemptions for small employers, and the range of conditions
      covered by the law.

PMID- 17556380
TI  - Substance abuse benefits: still limited after all these years.
AB  - Using data from a special supplement to the 2006 Kaiser/HRET Employer Health
      Benefits Survey, this study examines the state of employer-sponsored insurance
      substance abuse benefits in 2006 and how benefits compare to coverage for medical
      surgical services. In 2006, 88 percent of insured workers had some coverage for
      substance abuse services. Current substance abuse benefits, however, do not
      provide the same protection afforded under medical-surgical benefits. Instead,
      substance abuse benefits are characterized by higher cost sharing and annual
      limits and lifetime limits on inpatient and outpatient care. These limits
      generally do not exist for other medical conditions and have increased since
      1990.

PMID- 17556381
TI  - Population genetic effects of urban habitat fragmentation in the perennial herb
      Viola pubescens (Violaceae) using ISSR markers.
AB  - BACKGROUND AND AIMS: Fragmentation of natural habitats can negatively impact
      plant populations by leading to reduced genetic variation and increased genetic
      distance as populations become geographically and genetically isolated from one
      another. To test whether such detrimental effects occur within an urban
      landscape, the genetic structure of six populations of the perennial herb Viola
      pubescens was characterized in the metropolitan area of Greater Cincinnati in
      southwestern Ohio, USA. METHODS: Using three inter-simple sequence repeat (ISSR)
      markers, 51 loci amplified across all urban populations. For reference, four
      previously examined agricultural populations in central/northern Ohio and a
      geographically distant population in Michigan were also included in the analysis.
      KEY RESULTS: Urban populations retained high levels of genetic variation
      (percentage of polymorphic loci, P(p) = 80.7 %) with similar genetic distances
      among populations and an absence of unique alleles. Geographic and genetic
      distances were correlated with one another, and all populations grouped according
      to region. Individuals from urban populations clustered together and away from
      individuals from agricultural populations and from the Michigan population in a
      principle coordinates analysis. Hierarchical analysis of molecular variance
      (AMOVA) revealed that most of the genetic variability was partitioned within
      populations (69.1 %) and among groups (22.2 %) of southwestern Ohio,
      central/northern Ohio and Michigan groups. Mean F(st) was 0.308, indicating
      substantial population differentiation. CONCLUSIONS: It is concluded that urban
      fragmentation does not appear to impede gene flow in V. pubescens in southwestern
      Ohio. These results are consistent with life history traits of this species and
      the possibility of high insect abundance in urban habitats due to diverse floral
      resources and nesting sites. Combined with the cleistogamous breeding system of
      this species, pollinator availability in the urban matrix may buffer populations
      against detrimental effects of habitat fragmentation, at least in larger forest
      fragments. Consequently, it may be inappropriate to generalize about genetic
      effects of fragmentation across landscapes or even across plant species with
      different pollination systems.

PMID- 17556382
TI  - Seed dormancy and germination of the European Chaerophyllum temulum (Apiaceae), a
      member of a trans-Atlantic genus.
AB  - BACKGROUND AND AIMS: The European Chaerophyllum temulum and two North American
      Chaerophyllum species have a trans-Atlantic disjunct distribution. This work
      aimed to resolve requirements for dormancy break and germination of C. temulum
      seeds and to compare dormancy traits with those of the two North American
      congeners. METHODS: Phenology of germination and embryo growth was studied by
      regularly exhuming seeds sown in natural conditions. Temperature requirements for
      embryo growth, breaking of dormancy and germination were determined by incubating
      seeds under controlled laboratory conditions. Additionally the effect of GA(3) on
      germination was tested to determine the specific dormancy type. KEY RESULTS: In
      natural conditions, embryo growth starts in early winter. Seedlings emerge in
      late winter shortly after the embryos reached the critical ratio for embryo
      length to seed length (E : S) of approx. 0.95. Growth of the embryo only occurs
      during a prolonged incubation period at 5 degrees C. After stratification at 5
      degrees C, which breaks physiological and morphological dormancy, seeds can
      germinate at a wide range of temperatures. GA(3) did not substitute for cold
      stratification in seeds placed at 23 degrees C. CONCLUSIONS: Chaerophyllum
      temulum has deep complex morphophysiological dormancy. This dormancy type differs
      considerably from that of the two North American congeners.

PMID- 17556383
TI  - Twenty-year trends in diagnosis of life-threatening neonatal cardiovascular
      malformations.
AB  - BACKGROUND: Infants with cardiovascular malformations are usually asymptomatic at
      birth. Earlier diagnosis is likely to improve outcome. OBJECTIVE: To examine
      trends in the diagnosis of potentially life-threatening cardiovascular
      malformations. METHODS: Ascertainment of all cardiovascular malformations
      diagnosed in infancy in the resident population of one English health region
      between 1985 and 2004. Infants with life-threatening cardiovascular malformations
      were all with hypoplastic left heart, pulmonary atresia with intact ventricular
      septum, transposition of the great arteries or interruption of the aortic arch;
      and those dying or undergoing operation within 28 days with coarctation of the
      aorta, aortic stenosis, pulmonary stenosis, tetralogy of Fallot, pulmonary
      atresia with ventricular septal defect or total anomalous pulmonary venous
      connection. RESULTS: Cardiovascular malformations were diagnosed in infancy in
      4444 of 690,215 live births (6.4 per 1000) and were potentially life threatening
      in 669 (15%). Overall, 55 (8%) were recognised prenatally, 416 (62%) postnatally
      before discharge from hospital, 168 (25%) in living infants after discharge and
      30 (5%) after death. Antenatal diagnoses increased from 0 to around 20% and no
      case was first diagnosed after death in the past 6 years. However, the proportion
      going home without a diagnosis remains around 25%. Malformations most likely to
      remain undiagnosed at discharge were coarctation of the aorta (54%), interruption
      of the aortic arch (44%), aortic valve stenosis (40%) and total anomalous
      pulmonary venous connection (37%). CONCLUSIONS: One in three infants with a
      potentially life-threatening cardiovascular malformation left hospital
      undiagnosed. Better early diagnosis is likely to be achieved by further
      improvements in antenatal diagnosis and more widespread use of routine pulse
      oximetry.

PMID- 17556384
TI  - Hypoxia, fetal growth and early origins of disease: the Andean curse on the
      Conquistadors.

PMID- 17556385
TI  - Out of the cleft: the source and target of extra-synaptic glutamate in the CA1
      region of the hippocampus.

PMID- 17556386
TI  - Feedforward vasodilatation at the onset of exercise.

PMID- 17556387
TI  - Elementary properties of spontaneous fusion of peptidergic vesicles: fusion pore
      gating.
AB  - The release of hormones and neurotransmitters by regulated exocytosis requires
      the delivery of secretory vesicles to the plasma membrane, where they dock and
      become primed for fusion with the plasma membrane. Upon stimulation a fusion pore
      is formed through which cargo molecules diffuse out of the vesicle lumen into the
      extracellular space. After the cargo release the fusion pore either closes (kiss
      and-run, transient exocytosis), fluctuates between an open and a closed state
      (for short times, fusion pore flickering, or for rather longer periods, 'pulsing
      pore') or expands irreversibly (full fusion exocytosis). In almost all secretory
      cells spontaneous secretion of vesicle cargo can be detected in the absence of
      stimulation. Spontaneous and stimulated exocytosis were thought to exhibit
      similar properties at elementary level, differing only in the probability of
      occurrence. However, recent studies indicate that spontaneous exocytosis differs
      from the stimulated one in many respects, therefore opening questions about the
      physiological role of spontaneous exocytosis. In this report we address the
      elementary properties of spontaneous and stimulated peptidergic vesicle discharge
      which appears to be modulated by fusion pore conductance (diameter) and fusion
      pore gating.

PMID- 17556388
TI  - Glucocorticoids and insulin both modulate caloric intake through actions on the
      brain.
AB  - Glucocorticoids act primarily in a feed-forward fashion on brain to activate CNS
      pathways that implement wanting appropriate to physiological needs. Thus,
      depending on the available conditions, elevated glucocorticoids may augment the
      behavioural want to run, fight or feed. Although glucocorticoids stimulate intake
      of chow, fat and sucrose, insulin appears to sculpt calorie-associated desires
      toward foods high in fat, acting through hepatic branch afferents of the vagus
      nerve. Both conditions of reduced food allowance and chronic stress excite
      glucocorticoid-augmented central neural networks that may lead toward ultimate
      abdominal obesity.

PMID- 17556389
TI  - Exercise hyperaemia in the heart: the search for the dilator mechanism.
AB  - Coronary blood flow is tightly coupled to myocardial oxygen consumption to
      maintain a consistently high level of myocardial oxygen extraction over a wide
      range of physical activity. This tight coupling has been proposed to depend on
      periarteriolar oxygen tension, signals released from cardiomyocytes (adenosine
      acting on K(ATP) channels) and the endothelium (prostanoids(,) nitric oxide,
      endothelin) as well as neurohumoral influences (catecholamines, endothelin), but
      the contribution of each of these regulatory pathways, and their interactions, to
      exercise hyperaemia in the human heart are still incompletely understood. Thus,
      in the human heart, nitric oxide, prostanoids, adenosine and K(ATP) channels each
      contribute to resting tone, but evidence for a critical contribution to exercise
      hyperaemia is lacking. In dogs K(ATP) channel activation together with adenosine
      and nitric oxide contribute to exercise hyperaemia in a non-linear redundant
      fashion. In contrast, in swine nitric oxide, adenosine and K(ATP) channels
      contribute to resting coronary resistance vessel tone control in a linear
      additive manner, but are not mandatory for exercise hyperaemia in the heart.
      Rather, exercise hyperaemia in swine appears to involve K(Ca) channel opening
      that is mediated, at least in part, by exercise-induced beta-adrenergic
      activation, possibly in conjunction with exercise-induced blunting of an
      endothelin-mediated vasoconstrictor influence. In view of these remarkable
      species differences in coronary vasomotor control during exercise, future studies
      are required to determine whether exercise hyperaemia in humans follows a canine
      or porcine control design.

PMID- 17556390
TI  - Prostaglandin E2 stimulates expression of osmoprotective genes in MDCK cells and
      promotes survival under hypertonic conditions.
AB  - The cells of the renal medulla produce large amounts of prostaglandin E2 (PGE2)
      via cyclooxygenases (COX)-1 and -2. PGE2 is well known to play a critical role in
      salt and water balance and maintenance of medullary blood flow. Since renal
      medullary PGE2 production increases in antidiuresis, and since COX inhibition is
      associated with damage to the renal medulla during water deprivation, PGE2 may
      promote the adaptation of renal papillary cells to high interstitial solute
      concentrations. To address this question, MDCK cells were exposed to a gradual
      tonicity increase in the presence or absence of 20 microM PGE2 prior to analysis
      of (i) cell survival, (ii) expression of osmoprotective genes (AR, BGT1, SMIT,
      HSP70 and COX-2), (iii) subcellular TonEBP/NFAT5 abundance, (iv) TonEBP/NFAT5
      transcriptional activity and (v) aldose reductase promoter activity. Cell
      survival and apoptotic indices after raising the medium tonicity improved
      markedly in the presence of PGE2. PGE2 significantly increased tonicity-mediated
      up-regulation of AR, SMIT and HSP70 mRNAs. However, neither nuclear abundance nor
      TonEBP/NFAT5-driven reporter activity were elevated by PGE2, but aldose reductase
      promoter activity was significantly increased by PGE2. Interestingly, tonicity
      induced COX-2 expression and activity was also stimulated by PGE2, suggesting the
      existence of a positive feedback loop. These results demonstrate that the major
      medullary prostanoid, PGE2, stimulates the expression of osmoprotective genes and
      favours the adaptation of medullary cells to increasing interstitial tonicities,
      an effect that is not explained directly by the presence of TonEs in the promoter
      region of the respective target genes. These findings may be relevant in the
      pathophysiology of medullary damage associated with analgesic drugs.

PMID- 17556391
TI  - Negligible direct lactate oxidation in subsarcolemmal and intermyofibrillar
      mitochondria obtained from red and white rat skeletal muscle.
AB  - We examined the controversial notion of whether lactate is directly oxidized by
      subsarcolemmal (SS) and intermyofibrillar (IMF) mitochondria obtained from red
      and white rat skeletal muscle. Respiratory control ratios were normal in SS and
      IMF mitochondria. At all concentrations (0.18-10 mm), and in all mitochondria,
      pyruvate oxidation greatly exceeded lactate oxidation, by 31- to 186-fold.
      Pyruvate and lactate oxidation were inhibited by alpha-cyano-4-hydroxycinnamate,
      while lactate oxidation was inhibited by oxamate. Excess pyruvate (10 mm)
      inhibited the oxidation of palmitate (1.8 mm) as well as lactate (1.8 mm). In
      contrast, excess lactate (10 mm) failed to inhibit the oxidation of either
      palmitate (1.8 mm) or pyruvate (1.8 mm). The cell-permeant adenosine analogue,
      AICAR, increased pyruvate oxidation; in contrast, lactate oxidation was not
      altered. The monocarboxylate transporters MCT1 and 4 were present on SS
      mitochondria, but not on IMF mitochondria, whereas, MCT2, a high-affinity
      pyruvate transporter, was present in both SS and IMF mitochondria. The lactate
      dehydrogenase (LDH) activity associated with SS and IMF mitochondria was 200- to
      240-fold lower than in whole muscle. Addition of LDH increased the rate of
      lactate oxidation, but not pyruvate oxidation, in a dose-dependent manner, such
      that lactate oxidation approached the rates of pyruvate oxidation. Collectively,
      these studies indicate that direct mitochondrial oxidation of lactate (i.e. an
      intracellular lactate shuttle) does not occur within the matrix in either IMF or
      SS mitochondria obtained from red or white rat skeletal muscle, because of the
      very limited quantity of LDH within mitochondria.

PMID- 17556392
TI  - Intracortical circuits modulate transcallosal inhibition in humans.
AB  - Previous results using paired-pulse transcranial magnetic stimulation (TMS) have
      suggested that the excitability of transcallosal (TC) connections between the
      hand areas of the two motor cortices is modulated by intracortical inhibitory
      circuits in the same way as corticospinal tract (CTS) projections to spinal
      motoneurons. Here we describe two further similarities in TC and CTS control
      using (1) an I-wave facilitation protocol and (2) preconditioning with rTMS. In
      experiment 1, excitability of TC pathways was measured using interhemispheric
      inhibition (IHI) and the ipsilateral silent period (iSP), whilst excitability of
      CTS pathways was measured by recording the EMG response evoked in the first
      dorsal interosseous muscle contralateral to the conditioning stimulus (cMEP). The
      intensity of the conditioning stimulus was first adjusted to threshold for
      evoking IHI and iSP, then pairs of conditioning stimuli were applied randomly at
      interstimulus intervals (ISIs) from 1.3 to 4.3 ms. IHI and iSP were facilitated
      at ISI=1.5 ms and 3.0 ms, respectively, as was the MEP evoked by the conditioning
      stimuli in the contralateral hand. We suggest that TC projections receive I-wave
      like facilitation similar to that seen in CTS projections. In experiment 2, short
      interval inhibition of the iSP (SICIiSP), and short interval intracortical
      inhibition of the cMEP (SICIcMEP) were examined before and after 600 pulses of 5
      Hz rTMS at 90% resting motor threshold. Both SICIiSP and SICIcMEP were reduced,
      as was the iSP; the cMEP was unchanged. This shows that the population of
      inhibitory interneurons that control TC neurons respond in the same way to 5 Hz
      rTMS as those that control CTS neurons. Taken together, the data from the two
      experiments suggest that the layer III and layer V pyramidal neurons that give
      rise to TC and CTS pathways, respectively, are controlled by neuronal circuitry
      with similar properties.

PMID- 17556393
TI  - Attenuated fever in rats during late pregnancy is linked to suppressed
      interleukin-6 production after localized inflammation with turpentine.
AB  - An attenuated fever response to pathogens during late pregnancy is a phenomenon
      that has been described in several mammalian species, and although mechanisms are
      not completely understood, decreased prostaglandin E2 (PGE2) synthesis has been
      implicated. Upstream of PGE2, there is evidence to suggest that anti-inflammatory
      cytokines such as interleukin-1 receptor antagonist (IL-1ra) could play a
      significant role. In the present study we addressed the role of pro-inflammatory
      cytokines during late pregnancy, specifically interleukin-6 (IL-6), an important
      circulating mediator in fever. Turpentine oil (TURP), a very potent pyrogen and
      activator of IL-6, was injected into the hind-limb muscle of rats at the 18th day
      of pregnancy (GD 18) or in non-pregnant (NP) age-matched female controls. As
      expected, TURP injection induced a highly significant fever in the NP animals,
      which peaked 11 h post-injection and lasted for over 24 h. This was accompanied
      by a significant rise in circulating IL-6 levels, which correlated with changes
      in PGE2 synthesizing enzymes expression in the hypothalamus. In complete
      contrast, TURP-induced fever was totally absent in GD 18 animals whose body
      temperature did not deviate from basal values. The lack of response was
      additionally reflected by the absence of change in IL-6 concentration and by the
      significant attenuation of PGE2 synthesizing enzymes expression, which correlated
      with the suppressed expression of SOCS3, a hypothalamic marker of IL-6 activity.
      Contrary to the changes in circulating IL-6 levels at GD 18, IL-1ra was induced
      to levels comparable to those of NP females, suggesting that the influence of
      this anti-inflammatory cytokine on the fever response to TURP is at best minimal.
      These data further confirm the importance of IL-6 in fever generation and provide
      evidence that it may be a key component of the attenuated fever response in late
      pregnancy.

PMID- 17556394
TI  - Cell content of phosphatidylinositol (4,5)bisphosphate in Ehrlich mouse ascites
      tumour cells in response to cell volume perturbations in anisotonic and in
      isosmotic media.
AB  - The labelling pattern of cellular phosphoinositides (PtdInsP(n)) was studied in
      Ehrlich ascites cells labelled in vivo for 24 h with myo-[2-(3)H]- or l-myo-[1
      (3)H]inositol and exposed to anisotonic or isosmotic volume perturbations. In
      parallel experiments the cell volume ([(14)C]3-OMG space) was monitored. In
      hypotonic media the cells initially swelled osmotically and subsequently as
      expected showed a regulatory volume decrease (RVD) response. Concurrently, the
      cell content of PtdInsP(2) showed a marked, transient decrease and the content of
      PtdInsP a small, transient increase. The changes in PtdInsP(2) and PtdInsP
      content increased progressively with the extent of hypotonicity (in the range
      1.00-0.50 relative osmolarity). No evidence was found for either hydrolysis of
      PtdInsP(2) or formation of PtdInsP(3). In hypertonic medium (relative osmolarity
      1.50), cells initially shrank osmotically and subsequently as expected showed a
      small regulatory volume increase (RVI) response. Concurrently, the cell content
      of PtdInsP(2) showed a marked increase and the content of PtdInsP a small
      decrease, i.e. changes in the opposite direction of those seen in hypotonic
      media. In isosmotic media with high (100 mm) or low (0.8 mm) K(+) concentration,
      cells slowly swelled or shrank due to uptake or loss of isosmotic KCl. Under
      these conditions, with largely unchanged intracellular ionic strength, the cell
      content of PtdInsP(2) and PtdInsP remained constant. Our results show that
      PtdInsP(2) is not volume sensitive per se, and moreover that the regulatory
      volume adjustments in Ehrlich ascites cells are not mediated by PtdInsP(2)
      hydrolysis and its subsequent production of second messengers. The simplest
      interpretation of the observed effects would be that PtdInsP(2) is controlled by
      ionic strength, probably via activation/inhibition of phosphoinositide-specific
      phosphatases/kinases. In Ehrlich ascites cells, as shown previously, the opposing
      ion channels and transporters activated during RVD and RVI, respectively, are
      controlled with tight negative coordination by a common cell volume 'set-point'
      that is shifted in anisotonic media, but unchanged during cell swelling in
      isosmotic high K(+) medium. We hypothesize that PtdInsP(2) might orchestrate this
      'set-point' shift.

PMID- 17556395
TI  - Sudden infant death syndrome in infants born to HIV-infected and opiate-using
      mothers.
AB  - OBJECTIVE: This study was undertaken to determine the role of opiate use during
      pregnancy as a predisposing factor for sudden infant death syndrome (SIDS) in
      infants born to HIV-infected mothers. METHODS: In order to identify all infant
      deaths and their cause and association with maternal opiate use, the data of a
      nationwide prospective cohort study of HIV-infected mothers and their children
      were extracted and analysed for a 13-year period. RESULTS: 24 (5.1%) infant
      deaths were observed out of 466 infants followed up until death or at least 12
      months of life. 3 (0.6%) of them were due to non-accidental trauma and were not
      associated with maternal opiate use. 7 (1.5%) died due to SIDS, which was
      confirmed by autopsy. All SIDS cases occurred in infants born to mothers
      reporting use of opiates during pregnancy (n = 124). The relative risk of SIDS
      compared to the general population was 18 (95% CI 9 to 38) for all infants of HIV
      infected mothers, and 69 (95% CI 33 to 141) for those with intrauterine opiate
      exposure (p<0.001). CONCLUSIONS: Compared to the Swiss general population, the
      risk for SIDS in this cohort of infants born to HIV-infected mothers was greatly
      increased, but only for mothers reporting opiate use during pregnancy. This
      effect appeared not to be mediated by prematurity, low birth weight, perinatal
      HIV infection or antiretroviral drug exposure.

PMID- 17556396
TI  - Are universal standards for optimal infant growth appropriate? Evidence from a
      Hong Kong Chinese birth cohort.
AB  - OBJECTIVE: In 2006 the World Health Organization (WHO) published new optimal
      growth standards for all healthy infants worldwide. To assess their general
      applicability to a recently transitioned Chinese population, we compared them
      with infant growth patterns in a representative sample of Hong Kong infants.
      DESIGN AND SETTINGS: Weight at birth and at 1, 3, 9, 12, 18 and 36 months, length
      at 3 and 9 months and height at 36 months were obtained for over 80% of all
      infants born in April and May 1997 (3880 boys and 3536 girls). Age and sex
      specific z scores were calculated relative to the WHO growth standards for term
      singletons. RESULTS: Weight for age was close to the 50th percentile of the WHO
      growth standards for both boys (mean z score: 0.00) and girls (0.04) at most time
      points before 3 years of age. However, our participants were shorter at 3 years,
      where the z scores in height were -0.34 and -0.38 for boys and girls,
      respectively. Restricting the analysis to a subset matching the WHO criteria for
      healthy infants without restrictions on growth gave similar results. CONCLUSIONS:
      Although the WHO study group concluded there was a striking similarity in
      length/height among different populations, Hong Kong Chinese toddlers are, on
      average, shorter. Epigenetic constraints on growth coupled with the rapid
      epidemiological transition in Hong Kong may not have allowed sufficient
      generations for infants and children to reach their full genetic height
      potential, and with it the WHO standards. A universal infant growth standard may
      not be appropriate across all populations.

PMID- 17556397
TI  - Peanut-free guidelines reduce school lunch peanut contents.
AB  - BACKGROUND: Some schools implement peanut-free guidelines (PFG) requesting
      omission of peanut from lunches. Our study assessed parental awareness of, and
      adherence to, PFG by comparing the percentage of lunches containing peanut
      between primary school classes with and without PFG in Montreal, Quebec. METHODS:
      Parents, school principals and teachers were queried concerning the school's PFG
      and children's lunches were inspected by a dietician for peanut-containing foods.
      RESULTS: When lunch peanut contents were compared in randomly selected
      classrooms, peanut was found in 5/861 lunches in classes with PFG (0.6%, 95% CI
      0.2% to 1.4%) and in 84/845 lunches in classes without PFG (9.9%, 95% CI 8.0% to
      12.2%), a 9.4% (95% CI 7.3% to 11.4%) difference. CONCLUSIONS: Our findings
      demonstrate that PFG are effective in reducing peanut in classrooms providing a
      basis for future research that should address whether or not the reduction in
      peanut achieved by restrictive lunch policies decreases the morbidity associated
      with peanut allergy in the school setting.

PMID- 17556398
TI  - Attention and executive functions in adolescents with spina bifida.
AB  - OBJECTIVE: This study was designed to examine attention processes and executive
      functioning in adolescents with spina bifida, and to explore whether impairment
      in these domains contributes to problems with social adjustment. METHODS: A
      sample of adolescents with spina bifida (n = 68) and a matched comparison group
      (n = 68) and their families were followed longitudinally. All participants
      completed questionnaires, and the adolescent participants underwent
      neurocognitive testing. RESULTS: The spina bifida sample showed greater
      impairment on objective and subjective measures of attention and executive
      functioning, even when differences in intellectual functioning were controlled.
      Additionally, attention and executive deficits were found to be predictive of
      social adjustment difficulties. A mediational analysis suggested the
      neurocognitive deficits mediate associations between spina bifida status and
      social adjustment difficulties. CONCLUSIONS: Adolescents with spina bifida appear
      to exhibit clear impairment in attention and executive functioning and this
      impairment may contribute to their well-established social difficulties.

PMID- 17556399
TI  - Brief report: intellectual and academic functioning in pediatric chronic kidney
      disease.
AB  - OBJECTIVE: Examine the intellectual and academic functioning in children with
      chronic kidney disease (CKD). METHODS: Using a cross-sectional design, children
      with CKD (n = 30) were compared to matched controls (n = 41) on measures of
      intelligence, achievement, and rates of learning disabilities (LD) variously
      defined. RESULTS: Children with CKD were at higher risk for grade retention (p <
      .001) and absenteeism (p < .01), and evidenced mild impairments on measures of
      intelligence (p < .001), math (p < .01), reading (p < .05), and satisfied
      criteria for a low achievement definition of LD (p < .01) more frequently than
      control group participants. Renal function was a significant predictor (p < .02)
      of intellectual and academic scores in the CKD group. CONCLUSIONS: Educational
      and psychosocial supports are critical for children with CKD, and it may be
      important to monitor their cognitive functioning and academic progress over time.

PMID- 17556400
TI  - Peer functioning in children with ADHD.
AB  - This article describes what is currently known about the peer relationships of
      children with attention-deficit/hyperactivity disorder (ADHD). This topic is
      addressed both from the perspective of how ADHD initially contributes to
      problematic relationships with peers, and also from the perspective of how peers'
      reactions to these problems may serve to maintain them. Given the limited
      improvement typically obtained in treatment studies that use peer report measures
      as outcomes with ADHD samples and the well-documented predictive validity of peer
      reports for later adjustment, the need for more intensive interventions and novel
      approaches to address the peer problems of children with ADHD is emphasized.

PMID- 17556401
TI  - ADHD service use patterns in youth.
AB  - OBJECTIVE: To review what is currently known about service use by youth with
      attention-deficit/hyperactivity disorder (ADHD) and discuss research and policy
      implications. METHODS: Literature review. RESULTS: The primary care, mental
      health, and educational service system sectors all play an essential role in
      caring for youth with ADHD. Recent studies also suggest increasing use of
      stimulants and other psychoactive medication for youth with ADHD, decreasing
      mental health visits for ADHD unassociated with medication use, increased use of
      other psychotropic medications, and a number of barriers to care coordination
      across primary care, mental health, and schools. CONCLUSIONS: Four important
      services, research, and policy areas that need to be addressed over the next
      decade include: 1) delving deeper into current service use, 2) paying attention
      to the context in which service use occurs, 3) operationalizing evidence-based
      care for real-world settings, and 4) learning what changes clinician and educator
      behavior.

PMID- 17556402
TI  - The economic impact of attention-deficit/hyperactivity disorder in children and
      adolescents.
AB  - Using a cost of illness (COI) framework, this article examines the economic
      impact of attention-deficit/hyperactivity disorder (ADHD) in childhood and
      adolescence. Our review of published literature identified 13 studies, most
      conducted on existing databases by using diagnostic and medical procedure codes
      and focused on health care costs. Two were longitudinal studies of identified
      children with ADHD followed into adolescence. Costs were examined for ADHD
      treatment-related and other health care costs (all but 1 study addressed some
      aspect of health care), education (special education, 2 studies; disciplinary
      costs: 1 study), parental work loss (2 studies), and juvenile justice (2
      studies). Based on this small and as yet incomplete evidence base, we estimated
      annual COI of ADHD in children and adolescents at $14,576 per individual (2005
      dollars). Given the variability of estimates across studies on which that number
      is based, a reasonable range is between $12,005 and $17,458 per individual. Using
      a prevalence rate of 5%, a conservative estimate of the annual societal COI for
      ADHD in childhood and adolescence is $42.5 billion, with a range between $36
      billion and $52.4 billion. Estimates are preliminary because the literature is
      incomplete; many potential costs have not been assessed in extant studies.
      Limitations of the review and suggestions for future research on COI of ADHD are
      provided.

PMID- 17556403
TI  - A family-centered approach to planning and measuring the outcome of interventions
      for children with attention-deficit/hyperactivity disorder.
AB  - This paper discusses a set of closely related parenting and family factors that
      should be considered when planning and measuring the outcome of interventions for
      children with attention-deficit/hyperactivity disorder (ADHD). These include
      parenting and parent-child relationships, parental cognitions, parental
      adjustment, marital interactions, general family relationships, and adaptive
      child functioning within the family. The measurement of each construct is
      discussed, and comparative, longitudinal, and treatment outcome studies using
      these measures are reviewed. It is concluded that measures of treatment outcome
      for children with ADHD could be improved by utilizing multiple informants,
      developing tools with greater content and contextual validity, relying more on
      observational methods, and identifying those measures which are of greatest
      importance to families. Given the multiple pathways via which both psychosocial
      and pharmacological interventions exert their influence, composite measures
      combining multi-informant, multimethod constructs may represent more useful
      measures of treatment outcome than measures of primary ADHD symptoms.

PMID- 17556404
TI  - Measurement of ADHD outcomes: implications for the future.

PMID- 17556405
TI  - Attention-deficit/hyperactivity disorder: diagnosis, lifespan, comorbidities, and
      neurobiology.
AB  - In this report, we provide an evidence-based overview of attention
      deficit/hyperactivity disorder (ADHD), including diagnosis, prevalence,
      developmental expression of symptoms, persistence, the heterogeneity of
      functional outcome, impairment in afflicted adults, psychiatric comorbidity,
      pathophysiology, genetics, psychosocial and biologic risk factors, and
      neurobiology. Attention-deficit/hyperactivity disorder is an early-onset, highly
      prevalent neurobehavioral disorder, with genetic, environmental, and biologic
      etiologies, that persists into adolescence and adulthood in a sizable majority of
      afflicted children of both sexes. It is characterized by behavioral symptoms of
      inattention, hyperactivity, and impulsivity across the life cycle and is
      associated with considerable morbidity and disability. Comorbidity is a distinct
      clinical feature of both childhood and adult ADHD. Although its etiology remains
      unclear, emerging evidence documents its strong neurobiologic and genetic
      underpinnings. Despite the high diagnostic reliability and the robust evidence of
      the validity of ADHD, there are many underlying issues that remain to be
      resolved. These include establishing developmentally appropriate diagnostic
      criteria at older ages, further elaborating the impact of gender on symptom
      expression, and examining risk and protective factors in relationship to
      prevention or amelioration of ADHD as well as related functional impairments.

PMID- 17556406
TI  - Predicting early renal allograft function using clinical variables.
AB  - BACKGROUND: Suboptimal early graft function following renal transplantation
      remains a significant challenge. It is suggested that clinical variables (or
      scoring systems based thereon) may predict the occurrence of delayed graft
      function (DGF), defined as post-operative dialysis requirement. However, data is
      conflicting, and suboptimal renal function not requiring dialysis has been little
      investigated. This study tested the ability of clinical variables to predict
      suboptimal early function variably assessed by: (i) DGF (dialysis requirement
      during the first week); (ii) DGF duration; (iii) slow graft function
      (creatinine>3 mg/dl on day 5); (iv) creatinine reduction ratio on day 2. METHODS:
      Details on 217 consecutive renal transplant recipients were collected. All
      received ciclosporin-based immunosuppression. Multiple regression analysis was
      used to assess the association between individual clinical variables and
      suboptimal early graft function. Also tested were three scoring systems
      incorporating clinical variables [US Renal Database System (USRDS score),
      deceased donor score (DDS) and expanded criteria donor kidneys]. Receiver
      operated-characteristic curve analysis was used to assess the predictive power of
      clinical variables and scoring systems. RESULTS: Early graft function was
      associated with donor age, donor body mass index, donor hypertension, donation
      following cardiac death, black recipient ethnicity, recipient weight and cold
      ischaemic time (P<or=0.05 for all). All scoring systems showed associations with
      early graft function, although only USRDS score remained in the multiple
      regression model. The overall utility of the USRDS score in predicting DGF was
      moderate at best, although improved at extreme scores (specificity: 95%; positive
      predictive value: 73%; for USRDS score>or=150). CONCLUSIONS: Clinical variables
      and scores have moderate predictive ability for early graft function and although
      of potential use in clinical practice, caution should be exercised before
      altering patient management based solely on them.

PMID- 17556407
TI  - Serum erythropoietin concentrations and responses to anaemia in patients with or
      without chronic kidney disease.
AB  - BACKGROUND: Renal anaemia is caused by a relative erythropoietin (EPO)
      deficiency. Due to difficult interpretation of serum EPO concentrations adapted
      to anaemia and renal function, the diagnostic value of measuring serum EPO
      concentrations is limited. METHODS: We retrospectively analysed the relationship
      between haemoglobin and serum EPO concentrations routinely measured in in- and
      out-patients of our university hospital from 2001-04. Patients under EPO
      substitution or those with acute renal failure, polycystic kidney disease, renal
      carcinoma or polycythaemia due to pulmonary disease were excluded. The study
      population (n = 500) was then stratified according to the presence or absence of
      chronic kidney disease (CKD) and to the stage if CKD was present. EPO
      concentrations were expressed in percentiles corrected for the severity of
      anaemia and based on the EPO response in patients without CKD. RESULTS: In
      patients without CKD (n = 167) there was a strong parametric correlation between
      severity of anaemia and increase in EPO (r = -0.81). Linear regression of the log
      transformed EPO values revealed the equation log EPO (mIU/ml) = -0.135 x Hb
      (g/dl) + 2.821 (r(2) = 0.65). With increasing stages of CKD the correlation
      between haemoglobin and EPO concentrations was gradually attenuated and was
      completely lost in CKD stage four and five. In anaemic patients with Hb < 11
      g/dl, relative EPO deficiency defined as EPO concentrations below the 25th
      percentile was present in 38%, 67%, 93% and 100% of the patients with CKD stages
      1-5, respectively. CONCLUSIONS: Expression of EPO concentrations in percentiles
      improves the diagnostic value of measuring EPO concentrations for diagnosing
      relative EPO deficiency and renal anaemia.

PMID- 17556409
TI  - Direct renin inhibitors: the dawn of a new era, or just a variation on a theme?

PMID- 17556408
TI  - Haemodynamic and renal effects of endothelin receptor antagonism in patients with
      chronic kidney disease.
AB  - BACKGROUND: Endothelin-1 (ET-1) has been implicated in the pathophysiology of
      chronic kidney disease (CKD) and ET receptor blockade has shown renoprotective
      effects in animals. We examined the haemodynamic and renal effects of an ET
      receptor antagonist, TAK-044, in patients with CKD. METHODS: Seven patients with
      CKD (mean arterial pressure 103 mmHg; mean plasma creatinine 3.5 mg/dl) received
      three 15 min intravenous infusions, each separated by at least 7 days, of either
      placebo or TAK-044 (100 or 750 mg) in a randomized, double blind crossover study.
      Systemic and renal haemodynamics, and plasma immunoreactive ET-1, big ET-1 and C
      terminal fragment concentrations, were determined before and after the infusions
      of placebo and drugs. RESULTS: Compared with placebo, TAK-044 reduced mean
      arterial pressure (MAP) (100 mg: 7.4 +/- 1.9 mmHg, 750 mg: 8.4 +/- 2.3 mmHg, P <
      0.01) and systemic vascular resistance index (100 mg: 650 +/- 140 dyne.s.cm(
      5).m(-2), 750 mg: 829 +/- 141 dyne.s.cm(-5).m(-2), P < 0.01) at both doses. TAK
      044 increased cardiac index and heart rate to a similar degree at both doses.
      With regards to renal haemodynamics, TAK-044 had no significant effect on the
      glomerular filtration rate at either dose but tended to increase renal plasma
      flow (100 mg: 9.6 +/- 5.0 ml/min, 750 mg: 25.3 +/- 19.5 ml/min) and decreased the
      effective filtration fraction (100 mg: 3.6 +/- 1.1%, 750 mg: 4.7 +/- 1.7%, P <
      0.01), in a dose-dependent manner. TAK-044 had no significant effect on sodium or
      lithium clearance, or on fractional excretion of sodium and lithium. Plasma ET-1
      concentrations rose more than two-fold after 750 mg TAK-044 while big ET-1 and C
      terminal fragment concentrations were unchanged. CONCLUSIONS: These findings
      suggest an important role for ET-1 in controlling systemic and renal
      haemodynamics in patients with CKD. The antihypertensive and potentially
      renoprotective actions of ET receptor antagonists shown in this study may prove
      useful in slowing the progression of CKD. Clinical trials are now needed to
      address these key questions for CKD.

PMID- 17556410
TI  - Procalcitonin as marker of infection in patients with Goodpasture's syndrome is
      misleading.
AB  - BACKGROUND: Procalcitonin (PCT) is routinely measured to differentiate autoimmune
      disorders from infection. There are reports, however, where PCT is high in the
      absence of infection, i.e. in vasculitis. To investigate the value of PCT in
      Goodpasture's syndrome, we reviewed the charts of patients with Goodpasture's
      syndrome who were treated from 1996 to 2006. METHODS: PCT (normal range<0.5
      ng/ml) was measured with an immunoluminometric assay, C-reactive protein (CRP;
      normal range<5 mg/l) with nephelometry. Anti-glomerular basement membrane
      antibodies (normal range<1:10) were measured with ELISA. RESULTS: During the last
      10 years we diagnosed seven patients with Goodpasture's syndrome. Six out of
      seven patients had biopsy proven crescentic and necrotizing glomerulonephritis.
      Five patients had a severe manifestation with pulmonary involvement (n=3) and/or
      severe renal insufficiency (n=4). Mean CRP levels were 145.7 mg/l, mean PCT
      levels were 34.1 ng/ml. Therapy consisted of plasmapheresis (n=3), pulse
      cyclophosphamide therapy (n=4) and glucocorticoids (n=6). Remarkably, all
      patients with elevated PCT levels had life-threatening disease (n=4) and remained
      dialysis-dependent (as compared to with only one out of three patients with
      normal PCT). In two out of five patients with severe Goodpasture's syndrome, PCT
      levels remained high. After thorough exclusion of infection, resumption of high
      dose glucocorticoids normalized PCT and CRP levels. CONCLUSIONS: The measurement
      of PCT as a marker of infection in patients with Goodpasture's syndrome is
      misleading. High PCT values might rather point to a severe form of Goodpasture's
      syndrome with a more unfavourable prognosis. However, further studies with larger
      patient numbers are needed to prove this hypothesis.

PMID- 17556412
TI  - IgA nephropathy in a patient with IgG lambda light-chain plasmacytoma: a rare
      coincidence.

PMID- 17556411
TI  - Trace element removal during in vitro and in vivo continuous haemodialysis.
AB  - BACKGROUND: Continuous renal replacement therapy (CRRT) increasingly is being
      used to treat critically ill patients with renal disease. CRRT removes waste
      products but also nutrients. Our understanding of trace element CRRT clearance
      has been limited by poor assay sensitivity. The development of inductively
      coupled plasma mass spectrometry (ICP-MS) allows for the measurement of CRRT
      trace element removal. METHODS: Continuous venovenous haemodialysis (CVVHD)
      transmembrane clearances of trace elements and urea were assessed using a bovine
      blood-based in vitro model using two different haemodialyser types. These
      findings were validated in 10 critically ill adult patients receiving continuous
      venovenous haemodiafiltration (CVVHDF). Calculated daily trace element loss was
      compared with a typical dose of daily trace element supplementation. RESULTS: The
      mean +/- SD in vitro CVVHD transmembrane clearances (ml/min) for the polysulfone
      haemodialyser were chromium 0.97 +/- 0.23, copper 0.47 +/- 0.18, manganese 4.6 +/
      3.6, selenium 1.2 +/- 0.63 and zinc 2.3 +/- 0.32 and for the cellulose diacetate
      haemodialyser chromium 1.54 +/- 0.91, copper 0.21 +/- 0.07, manganese 7.8 +/-
      4.1, selenium 0.76 +/- 0.39 and zinc 2.7 +/- 0.37. The in vivo CVVHDF
      transmembrane clearances (ml/min) were chromium 5.4 +/- 2.4, copper 0.45 +/-
      0.33, manganese 1.9 +/- 4.6, selenium 1.6 +/- 1.2, and zinc 4.0 +/- 1.3.
      CONCLUSION: ICP-MS assays detected the five trace elements in the effluent of
      CVVHDF patients. Trace element CVVHD transmembrane clearance estimates for our in
      vitro model were supported by the in vivo CVVHDF findings. Calculated daily trace
      element loss attributed to CVVHD and CVVHDF with dialysate flow rates of 33.3
      ml/min is less than what is provided in a daily dose of a trace element
      supplementation product.

PMID- 17556413
TI  - Pentoxifylline as treatment for uraemic pruritus--an addition to the weak
      armentarium for a common clinical symptom?

PMID- 17556414
TI  - Long-term outcome of repeated lead chelation therapy in progressive non-diabetic
      chronic kidney diseases.
AB  - BACKGROUND: Previous research suggest that repeated lead-chelation therapy
      decelerates progression of renal insufficiency in non-diabetic (non-DM) patients
      with high-normal body lead burden (BLB). Study findings are limited by relatively
      short-term follow-up and small sample size. METHODS: A total of 116 non-DM
      patients with chronic kidney diseases (serum creatinine level of 1.5-3.9 mg/dl),
      high-normal BLB (>60 microg and <600 microg) and no lead exposure history were
      randomly assigned to a chelation or control group in this 4-year clinical trial.
      For 3 months, the 58 chelation group patients received initial lead-chelation
      therapy with calcium disodium EDTA, and the 58 control group patients received
      placebos. During the ensuing 48 months, repeated chelation therapy was
      administered weekly to chelation group patients unless, on repeated testing, BLB
      was <60 microg; the control group patients received weekly placebo infusions for
      5 weeks at 6-month intervals. RESULTS: Mean change in the glomerular filtration
      rate (GFR) in the chelation group was -1.8 +/- 8.8 ml/min/1.73 m(2), as compared
      with -12.7 +/- 8.4 ml/min/1.73 m(2) in the control group (P <0.0001) at study
      end. Chelation group rates of decline in the GFR was lower than that in the
      control group, although they had similar decline rates before chelation. At study
      end, 18 patients, including 15 control group patients, had elevated serum
      creatinine levels to two times the baseline values. Both Cox and Kaplan-Meier
      analysis demonstrated repeated chelation therapy was the important determining
      factor of progression of renal insufficiency. CONCLUSIONS: Repeated chelation
      therapies can, over a four-year period, slow progression of renal insufficiency
      in non-DM patients with high-normal BLB.

PMID- 17556415
TI  - Sodium intake determines the role of adenosine A2 receptors in control of renal
      medullary perfusion in the rat.
AB  - BACKGROUND: In the kidney, adenosine (ADO) can induce either vasoconstriction or
      vasodilatation, mediated by A1 or A2 receptors, respectively. The vasodilator
      influence may be of special importance in the renal medulla which operates at low
      tissue pO(2) levels and is susceptible to ischaemic damage. It has not been
      established if ADO induced vasodilatation is modified by salt intake. METHODS: We
      examined effects of stimulation or inhibition of ADO receptors (A2R) on perfusion
      of the renal cortex and medulla on low- or high- sodium intake (LS, HS). Effects
      of suprarenal aortic ADO (0.03 mmol/kg/h), A2R agonist (DPMA), 0.08-0.4
      mmol/kg/h, or antagonist (DMPX), 1.7 micromol/kg/h, were examined in
      anaesthetized rats maintained on LS (0.15% Na) or HS (4% Na) diet for 3 weeks.
      Whole kidney blood flow (RBF) and the perfusion (laser-Doppler) of the
      superficial cortex and outer and inner medulla (OM-BF, IM-BF) were measured.
      RESULTS: In LS rats neither drug changed renal perfusion. In HS rats ADO
      increased RBF 18 +/- 3%, OM-BF 16 +/- 7% and IM-BF 16 +/- 6%. IM-BF increased
      after DPMA 18 +/- 5% and decreased after DMPX 13 +/- 3%; neither drug
      consistently changed perfusion of the cortex. CONCLUSIONS: On HS intake,
      medullary perfusion is controlled by ADO vasodilator (A2) receptors, which may
      help provide adequate oxygen to the medulla, the zone which normally operates
      under relative hypoxia. On LS intake, the vasodilator and vasoconstrictor effects
      are probably in balance and ADO has little role in control of intrarenal
      circulation.

PMID- 17556416
TI  - High salt intake: a cause of blood pressure-independent left ventricular
      hypertrophy?

PMID- 17556417
TI  - Chronic kidney disease stage in renal transplantation classification using
      cystatin C and creatinine-based equations.
AB  - BACKGROUND: Current clinical guidelines recommend that renal transplant
      recipients (RTRs) be classified into chronic kidney disease (CKD) stage using a
      creatinine-based estimate of glomerular filtration rate (GFR). However,
      creatinine-based equations are inaccurate in RTRs leading to frequent CKD stage
      misclassification. It is not known whether the classification of CKD stage would
      be improved using a cystatin C-based estimate of GFR. METHODS: We measured
      (99m)Tc-DTPA GFR, cystatin C and creatinine in 198 stable RTRs. GFR was estimated
      using cystatin C-based equations (Filler, Le Bricon and Rule) and four creatinine
      based equations. We determined the proportion, overall and by CKD stage, that
      were classified correctly by each equation as compared to the (99m)Tc-DTPA GFR.
      RESULTS: The Filler equation correctly classified 76% of patients compared to
      only 65% with the abbreviated modification of diet in renal disease (MDRD)
      equation and 69% with the Cockcroft-Gault equation. In CKD stages two and four,
      the Filler equation correctly classified 77% and 60% of patients whereas the
      abbreviated MDRD equation correctly classified 46% and 93% of patients. The area
      under the curve by receiver operating curve analysis for overall stage
      classification was uniformly poor for all equations (0.52-0.56). CONCLUSIONS: The
      cystatin C-based Filler and Le Bricon GFR estimates classified slightly more
      patients into the correct CKD stage than the standard creatinine-based equations
      in stable RTRs although the overall diagnostic accuracies were similar. The
      differences are modest and prospective studies will be needed to determine if the
      adoption of these equations for classification would lead to improved recognition
      of CKD complications or patient care.

PMID- 17556418
TI  - Iron availability and complex stability of iron hydroxyethyl starch and iron
      dextran a comparative in vitro study with liver cells and macrophages.
AB  - BACKGROUND: Intravenous iron (IVI) therapy is required in patients with end-stage
      renal disease (ESRD) under chronic haemodialysis (HD). In this in vitro study we
      investigated the availability and stability of iron hydroxyethyl starch (iron
      Hes) compounds in THP-1 cells (macrophage phenotype) and liver cells (HepG2
      cells) and compared it with the well-known iron dextran. METHODS: The uptake and
      release of these iron formulations by THP-1 cells (macrophage phenotype) and
      HepG2 cells were investigated with atomic absorption spectrometry (AAS). Ferritin
      was measured by ELISA. HepG2 cells were used to investigate effects of IVI on the
      intracellular labile iron pool (LIP), which was measured by using the fluorescent
      calcein assay. The amount of redox-active iron within the iron formulations was
      assayed using dichlorofluorescein as fluorescent probe. RESULTS: All iron
      preparations were taken up, stored in ferritin and released again by macrophages
      and HepG2-cells. This study shows that the availability and stability of iron-HES
      formulations in vitro are comparable with the well-known iron dextran compounds.
      CONCLUSIONS: Our results indicate that these new iron formulations have a good
      stability and availability in vitro and are comparable with the well-known iron
      dextran complexes.

PMID- 17556419
TI  - Impact of kidney transplantation on sleep apnoea in patients with end-stage renal
      disease.
AB  - BACKGROUND: Sleep apnoea is common in patients with end-stage renal disease.
      Although individual case reports have described an improvement in sleep apnoea
      following kidney transplantation, there have been no longitudinal studies of a
      case series to determine what proportion of patients with sleep apnoea improve.
      METHODS: Dialysis-dependent patients awaiting kidney transplantation and pre
      dialysis patients with an identified living donor kidney had overnight
      polysomnography, which was repeated several months after successful kidney
      transplantation. Patients were divided into apnoeic and non-apnoeic groups based
      on an apneoa-hypopnoea index (AHI) > 10/h during pre-transplant polysomnography
      and, following transplantation, apnoeic patients were further divided into
      responders and non-responders based on >50% reduction in AHI and/or AHI < 10/h.
      RESULTS: Eighteen patients (11 men, 7 women), aged 27-65, were studied. Pre
      transplant sleep apnoea was present in 11 of 18 (61%) patients. Although
      transplantation was associated with a significant reduction in blood urea
      nitrogen and serum creatinine, there were no significant changes in AHI (pre vs
      post: 20.2 +/- 15.1 vs 23.5 +/- 21.3). Among the 11 apnoeic patients, only three
      met the criteria for a significant improvement ('responder'). There were no
      patient characteristics, sleep apnoea indices or renal function changes that
      distinguished responders from non-responders. CONCLUSIONS: Sleep apnoea improves
      in a minority of patients with end-stage renal disease following successful
      kidney transplantation. Specific determinants of improvement were not identified.

PMID- 17556420
TI  - Incomplete distal renal tubular acidosis affects growth in children.
AB  - BACKGROUND: Incomplete distal renal tubular acidosis (idRTA) is recognized as an
      underlying aetiology in recurrent nephrolithiasis. Until the recently reported
      high prevalence of idRTA in adults with osteoporosis, the effect of idRTA on
      skeletal parameters was not known. We hypothesize that idRTA has a potential to
      affect height in the paediatric population. METHODS: In a cross-sectional study,
      the children with posterior urethral valves (PUV), with normal estimated
      glomerular filtration rates, were evaluated for idRTA and complete dRTA. The
      idRTA evaluation was done by short ammonium chloride acidification test. The
      height standard deviation scores (SDS) in the idRTA group were compared with PUV
      children without dRTA, with complete dRTA, and to age and gender matched controls
      with no renal issue (n = 50). RESULTS: The idRTA group (n = 17) manifested a
      significantly lower mean height SDS (-1.94 +/- 0.41 vs -0.46 +/- 0.28; P < 0.001)
      and a higher short stature prevalence (height SDS below 2) (18% vs 0; P = 0.06)
      as compared with those without dRTA (n = 23). The matched controls showed a
      significantly higher height SDS as compared with the idRTA group (-0.39 +/- 0.25
      vs -1.94 +/- 0.41; P < 0.001). As compared with the complete dRTA group (n = 9),
      the children with idRTA did have significantly higher height SDS (-1.94 +/- 0.41
      vs -5.31 +/- 1.95; P = 0.002), and a lower short stature prevalence (18% vs 78%;
      P = 0.001). On multivariate analysis, dRTA was significantly associated with the
      height SDS (= -0.88; P < 0.001). CONCLUSIONS: Incomplete dRTA affects height in
      children. This observation needs validation in longitudinal studies.

PMID- 17556421
TI  - Effects of NH4Cl-induced systemic metabolic acidosis on kidney mitochondrial
      coupling and calcium transport in rats.
AB  - BACKGROUND: We have previously shown that chronic metabolic acidosis, induced in
      rats by NH(4)Cl feeding, leads to nephron hypertrophy and to a decreased water
      salt reabsorption by the kidneys. Since mitochondria are the main source of
      metabolic energy that drives ion transport in kidney tubules, we examined energy
      linked functions (respiration, electrochemical membrane potential and coupling
      between respiration and ADP phosphorylation) in mitochondria isolated from rat
      kidney and liver at 48 h after metabolic acidosis induced by NH(4)Cl. METHODS:
      Mitochondria isolated from the kidneys and liver of metabolic acidotic rats,
      induced by NH(4)Cl, was used to study of the oxygen consumption by Clark-type
      electrode, mitochondrial electrical transmembrane potential estimated by the
      safranine O method and the variations in free medium Ca(2+) concentrations
      examined by absorbance spectrum of Arsenazo III set at the 675-685 nm wavelength
      pair. RESULTS: Whole kidney and liver mitochondria isolated from 48 h acidotic
      rats presented higher resting respiration, lower respiratory control and a lower
      ADP/O ratio than controls. These differences in mitochondrial coupling, between
      respiration and oxidative phosphorylation (ATP synthesis), were totally corrected
      when experiments were carried out in the presence of carboxyatractyloside, GDP
      and BSA, indicating that mitochondrial uncoupling proteins are more active in
      acidotic rat kidneys. Interestingly, determination of Ca(2+) transport
      demonstrated a faster rate of initial Ca(2+) uptake by acidotic kidney
      mitochondria, which resulted in a lower concentration of extra-mitochondrial
      Ca(2+) under steady-state conditions (Ca(2+) set point) when compared with
      control mitochondria. In contrast, there were no significant differences in the
      rates of Na(+) or ruthenium red induced Ca(2+) efflux. CONCLUSIONS: We suggest
      that the mild uncoupling and higher Ca(2+) accumulation represents an adaptation
      of the mitochondria to cope with conditions of oxidative stress and high
      cytosolic Ca(2+), which are associated with a decreased efficiency of oxidative
      phosphorylation that may explain, at least in part, the striking natriuresis
      observed under chronic acidosis. Finally, there were no changes in Ca(2+)
      transport or coupling in liver mitochondria isolated from the acidotic rats.

PMID- 17556422
TI  - Bilateral incomplete double ureters.

PMID- 17556423
TI  - In vitro and in vivo evaluation of an oscillometric device for monitoring blood
      pressure in dialysis patients.
AB  - BACKGROUND: Nowadays, an increasing number of dialysis machines lodge a blood
      pressure (BP) measuring device, whose accuracy has a clear implication for the
      patients' clinical management. METHODS: An automated oscillometric
      sphygmomanometer (HD-BPM by Gambro Dasco) used during haemodialysis was submitted
      to both in vitro and in vivo tests, in order to evaluate some modifications aimed
      at improving measurement accuracy and consistency. The results were compared with
      those obtained by another oscillometric monitor (BX-100 by Colin). Three steps of
      evaluation were followed. First, the maintenance of the overall accuracy
      requirements prescribed by ANSI/AAMI SP-10 standard was verified. Then, an in
      vitro validation was carried out by using a test simulator. Finally, during a
      multi-centre field trial, 392 BP measurement sessions on 53 dialysis patients
      were collected. Every session consisted of two consecutive intra-dialysis
      measurements by the oscillometric monitors, each one performed simultaneously to
      an auscultatory measurement. A comparison with the intra-arterial method was
      performed as well. RESULTS: When compared with an in vivo data set previously
      collected, the HD-BPM accuracy complied with required limits. Second, the
      internal repeatability with respect to the simulator was satisfactory (SD of the
      differences between device and simulator readings: HD-BPM: systolic = 5.7,
      diastolic = 4.2; BX-100: systolic = 4.2, diastolic = 5.5 mmHg). Moreover, the
      comparison between oscillometric and auscultatory methods during in vivo trial
      gave similar results for the two monitors, even if systolic pressure SD exceeds
      the limit recommended by ANSI/AAMI SP-10 (mean value of the differences +/- SD:
      HD-BPM: systolic = 0.5 +/- 9.0, diastolic = 1.5 +/- 6.9; BX-100: systolic = 3.1
      +/- 8.2, diastolic = -2.0 +/- 7.6 mmHg). CONCLUSIONS: These data underline the
      importance of performing accuracy evaluations for BP monitors in the conditions
      where they normally work, by using well-accepted protocols.

PMID- 17556424
TI  - A primer on iron therapy.

PMID- 17556425
TI  - Increasing fill volume reduces cardiac performance in peritoneal dialysis.
AB  - BACKGROUND: It is generally accepted that peritoneal dialysis (PD) affects
      systemic haemodynamics less than haemodialysis, but little is known about changes
      in haemodynamics during PD. It is unknown if increasing PD volume causes changes
      in cardiovascular haemodynamics possibly increasing the demand on the heart even
      during normal daily activities. METHODS: Fifteen stable PD patients were included
      in this randomized, controlled, open-label crossover study. After drainage, we
      measured blood pressure, pulse rate and cardiac output (CO) after 30 min in the
      supine position. The measurements were repeated 5 min later in an upright
      position. Subsequently, following fill, the measurements were repeated after 30
      min in the supine and 5 min later in the upright position. The two procedures
      were repeated twice. The fill was either 2 l or 3 l of dialysate. CO was measured
      with a non-invasive device based on foreign gas rebreathing. Stroke volume (SV)
      and total peripheral systemic resistance were calculated. RESULTS: In the supine
      position, no difference was found between drained and 2 l fill. With 3 l fill
      both SV and CO decreased and total peripheral systemic resistance increased,
      while pulse rate and mean arterial blood pressure remained unchanged. In the
      upright position, SV and CO decreased and total peripheral systemic resistance
      increased. Pulse rate and mean arterial blood pressure were unchanged independent
      of fill volume when compared with the drained situation. During postural change,
      no significant differences were found between drained and 2 l and 3 l fill.
      CONCLUSION: The present study showed that cardiac performance decreased when
      increasing fill volume from 2 to 3 l in the supine position. The decreased
      cardiac performance was already present after 2 l fill in the upright position
      and did not change negatively by increasing fill. It was also shown that
      cardiovascular response from the supine to upright position was preserved.

PMID- 17556426
TI  - Hyperammonaemic encephalopathy and severe metabolic acidosis in a patient with
      chronic renal insufficiency years after ureterosigmoidostomy.

PMID- 17556428
TI  - Purtscher's retinopathy: epidemiology, clinical features and outcome.
AB  - AIMS: To study the incidence, systemic associations, presenting features and
      natural history of Purtscher's retinopathy in the UK and Ireland. METHODS: Cases
      were collected prospectively by active surveillance through the British
      Ophthalmological Surveillance Unit. Clinical details were obtained using an
      incident questionnaire, with follow-up at 1 and 6 months. RESULTS: Clinical
      details were obtained for 15 cases over 12 months. These were associated with
      road traffic accidents in 6 cases, chest compression in 6 cases and acute
      pancreatitis in 3 cases. All cases were symptomatic and presented with loss of
      visual acuity, visual field or a combination. Bilateral involvement was noted in
      9 cases. The acute retinal signs of cotton wool spots, retinal haemorrhage and
      Purtscher flecken cleared within 1 month in 26% of eyes and within 6 months in
      all eyes. The most common chronic signs were optic disc pallor and atrophy of the
      retinal pigment epithelium. Without treatment, 50% of eyes improved by at least 2
      Snellen lines at final follow-up and 23% improved by at least 4 Snellen lines.
      Only 1 of the 24 eyes had a final acuity worse than that recorded at
      presentation. CONCLUSION: Purtscher's retinopathy is a rare but sight-threatening
      eye condition, most commonly seen in young or middle-aged men and after trauma.
      Spontaneous visual recovery of at least 2 Snellen lines is seen in half of the
      cases.

PMID- 17556427
TI  - Biological response modifier therapy for refractory childhood uveitis.
AB  - PURPOSE: To evaluate the use of biological response modifiers (BRM) in the
      treatment of refractory childhood uveitis. DESIGN: Retrospective non-comparative
      case series of pediatric patients with uveitis treated with BRM. PARTICIPANTS: 23
      pediatric patients. METHODS: All children (18 years or younger) who received a
      BRM were assessed for visual changes, time to control inflammation, and any
      associated adverse side effects. Thirteen patients were treated with infliximab,
      five with adalimumab, and five with daclizumab. All patients had bilateral eye
      involvement. Diagnoses of the participants included juvenile idiopathic
      arthritis, keratouveitis, sarcoid panuveitis, Adamantiades-Behcets disease, and
      idiopathic panuveitis. MAIN OUTCOME MEASURES: Inflammation and visual acuity.
      RESULTS: In the infliximab group 16 of 26 eyes (62%), and 10 of 13 patients (77%)
      demonstrated an improvement in visual acuity. Twenty of 26 eyes (77%)
      demonstrated an improvement in the degree of inflammation. In the adalimumab
      group, four of 10 eyes (40%) demonstrated an improvement in visual acuity, with
      five of 10 eyes (50%) demonstrating an improvement in inflammation. Four of 10
      eyes (40%) in the daclizumab group demonstrated an improvement in vision with
      eight of 10 eyes (80%) demonstrating an improvement in inflammation. CONCLUSION:
      BRM appear to be safe to use in children, and represent a useful therapeutic
      adjunctive drug group for treating recalcitrant childhood uveitis.

PMID- 17556429
TI  - Effect of pupillary dilatation on glaucoma assessments using optical coherence
      tomography.
AB  - AIMS: To examine the effect of pupillary dilatation on the reliability of retinal
      nerve fibre layer (RNFL) and optic nerve head (ONH) assessments using Stratus OCT
      in a glaucoma clinic. METHODS: Observational study of 38 patients attending a
      glaucoma clinic. The "fast optic disc" and "fast RNFL thickness" programs on
      Stratus OCT were used to measure the RNFL thickness and ONH cup to disc ratio
      (CDR). Two scans were done before dilatation and two after dilatation with
      tropicamide 1% drops. The mean values and reproducibility before and after
      dilatation were compared, along with the quality of scans as indicated by the
      "signal strength" score. RESULTS: In nine patients (23.7%) no images were
      obtained undilated but after dilatation examination was possible in all patients.
      Inability to obtain an undilated scan was associated with smaller pupil size and
      increasing cataract. The scan quality, as judged by the signal strength score,
      was higher dilated than undilated for both RNFL thickness (p = 0.011) and ONH CDR
      (p = 0.007). Reproducibility was higher with dilated scans for RNFL thickness but
      not for ONH CDR. There were significant differences between the dilated and
      undilated examinations for three of the five RNFL thickness variables and two of
      the three ONH CDR categories. CONCLUSIONS: Acquisition of high quality OCT images
      was not possible without pupillary dilatation in about 25% of the patients. The
      dilated scans were more reproducible and of higher quality than the undilated
      scans. The two methods of examination do not appear to be interchangeable,
      suggesting that in follow up examinations the pupil should be in the same
      condition as at baseline. Pupillary dilatation is recommended before glaucoma
      assessments using Stratus OCT.

PMID- 17556430
TI  - Cataract prevalence, cataract surgical coverage and barriers to uptake of
      cataract surgical services in Pakistan: the Pakistan National Blindness and
      Visual Impairment Survey.
AB  - AIM: To estimate the prevalence of visual impairment and blindness caused by
      cataract, the prevalence of aphakia/pseudophakia, cataract surgical coverage
      (CSC) and to identify barriers to the uptake of cataract services among adults
      aged >or=30 years in Pakistan. METHODS: Probability proportional-to-size
      procedures were used to select a nationally representative sample of adults. Each
      subject underwent interview, visual acuity measurement, autorefraction, biometry
      and ophthalmic examination. Those that saw <6/12 in either eye underwent a more
      intensive examination procedure including corrected visual acuity, slit lamp and
      dilated fundus examination. CSC was calculated for different levels of visual
      loss by person and by eye. Individuals with <6/60 in the better eye as a result
      of cataract were interviewed regarding barriers. RESULTS: 16 507 Adults were
      examined (95.5% response rate). The crude prevalence of blindness (presenting
      <3/60 in the better eye) caused by bilateral cataract was 1.75% (95% CI 1.55%,
      1.96%). 1317 Participants (633 men; 684 women) had undergone cataract surgery in
      one or both eyes, giving a crude prevalence of 8.0% (95% CI 7.6%, 8.4%). The CSC
      (persons) at <3/60, <6/60 and <6/18 were 77.1%, 69.3% and 43.7%, respectively.
      The CSC (eyes) at <3/60, <6/60 and <6/18 were 61.4%, 52.2% and 40.7%,
      respectively. Cost of surgery (76.1%) was the main barrier to surgery.
      CONCLUSION: Approximately 570 000 adults are estimated to be blind (<3/60) as a
      result of cataract in Pakistan, and 3,560000 eyes have a visual acuity of <6/60
      because of cataract. Overall, the national surgical coverage is good but
      underserved populations have been identified.

PMID- 17556432
TI  - Physical activity and health.

PMID- 17556431
TI  - Selective serotonin reuptake inhibitors (SSRIs) and routine specialist care with
      and without cognitive behaviour therapy in adolescents with major depression:
      randomised controlled trial.
AB  - OBJECTIVE: To determine whether a combination of a selective serotonin reuptake
      inhibitor (SSRIs) and cognitive behaviour therapy (CBT) together with clinical
      care is more effective in the short term than an SSRI and clinical care alone in
      adolescents with moderate to severe major depression. DESIGN: Pragmatic
      randomised controlled superiority trial. SETTING: 6 outpatient clinics in
      Manchester and Cambridge. PARTICIPANTS: 208 adolescents, aged 11-17, with
      moderate to severe major or probable major depression who had not responded to a
      brief initial intervention. Adolescents with suicidality, depressive psychosis,
      or conduct disorder were included. INTERVENTIONS: 103 adolescents received an
      SSRI and routine care; 105 received an SSRI, routine care, and CBT. The trial
      lasted 12 weeks, followed by a 16 week maintenance phase. MAIN OUTCOME MEASURES:
      Change in score on the Health of the Nation outcome scales for children and
      adolescents (primary outcome) from baseline with 12 weeks as the primary and 28
      weeks as the follow-up end point. Secondary measures were change in scores on the
      mood and feelings questionnaire, the revised children's depression rating scale,
      the children's global assessment scale, and the clinical global impression
      improvement scale. RESULTS: At 12 weeks the treatment effect for the primary
      outcome was -0.64 (95% confidence interval -2.54 to 1.26, P=0.50). In a
      longitudinal analysis, there was no difference in effectiveness of treatment for
      the primary (average treatment effect 0.001, -1.52 to 1.52, P=0.99) or secondary
      outcome measures. On average there was a decrease in suicidal thoughts and self
      harm. There was no evidence of a protective effect of cognitive behaviour therapy
      on suicidal thinking or action. By 28 weeks, 57% were much or very much improved
      with 20% remaining unimproved. CONCLUSIONS: For adolescents with moderate to
      severe major depression there is no evidence that the combination of CBT plus an
      SSRI in the presence of routine clinical care contributes to an improved outcome
      by 28 weeks compared with the provision of routine clinical care plus an SSRI
      alone. TRIAL REGISTRATION: Current Controlled Trials ISRCNT 83809224.

PMID- 17556433
TI  - Teaching children basic life support skills.

PMID- 17556434
TI  - Treatment of epilepsy in developing countries.

PMID- 17556435
TI  - Control of methamphetamine misuse.

PMID- 17556436
TI  - Surgical solution is becoming acceptable, as for birth.

PMID- 17556437
TI  - Add carrying a card to QOF.

PMID- 17556438
TI  - Tell public about brain death.

PMID- 17556439
TI  - Is prognosis key in donation?

PMID- 17556440
TI  - First address informed consent in organ donation.

PMID- 17556441
TI  - Lessons from the disaster.

PMID- 17556442
TI  - Mass iron treatment is cheaper than routine deworming.

PMID- 17556443
TI  - Study shows wrong people, wrong skills, wrong tools . . .

PMID- 17556444
TI  - Drugs "refund" scheme proposed for England and Wales.

PMID- 17556446
TI  - Reed Elsevier to stop hosting arms exhibitions.

PMID- 17556447
TI  - Questions over human papillomavirus vaccine in the US and Australia.

PMID- 17556450
TI  - Germany may tighten its laws on sports medicine after doping incidents.

PMID- 17556448
TI  - Chinese court sentences former drug regulatory chief to death.

PMID- 17556451
TI  - Indian doctor arrested under antiterrorism law.

PMID- 17556453
TI  - Researcher accused of breaching research ethics faces GMC.

PMID- 17556452
TI  - AIDS and gay groups oppose Bush's nominee for surgeon general.

PMID- 17556454
TI  - Doctors advise women not to drink any alcohol during pregnancy.

PMID- 17556455
TI  - More women over 40 seek fertility treatment.

PMID- 17556459
TI  - Tuberculosis case exposes flaws in international public health systems.

PMID- 17556470
TI  - Cold Turkey.

PMID- 17556471
TI  - Faith based health policy: the urge to privatise.

PMID- 17556474
TI  - Should genetic information be disclosed to insurers? Yes.

PMID- 17556475
TI  - Should genetic information be disclosed to insurers? No.

PMID- 17556476
TI  - Formula estimation of glomerular filtration rate: have we gone wrong?

PMID- 17556477
TI  - Herpes zoster.

PMID- 17556478
TI  - Investigating hip pain in a well child.

PMID- 17556479
TI  - Management of psoriasis in pregnancy.

PMID- 17556480
TI  - Tiredness.

PMID- 17556481
TI  - Time to act on behalf of mentally disordered offenders.

PMID- 17556482
TI  - All together now.

PMID- 17556483
TI  - Wanted: stress monkeys.

PMID- 17556486
TI  - The use of ASB-14 in combination with CHAPS is the best for solubilization of
      human brain proteins for two-dimensional gel electrophoresis.
AB  - Protein extraction is the most important step to reveal a proteome by Two
      Dimensional Gel Electrophoresis. Usually, the urea/thiourea based standard
      protein extraction buffer (SB) is combined with detergents with the aim of
      achieving better resolution and solubilization of different classes of proteins.
      In order to produce better gels and achieve the greatest spot resolution of Human
      Brain Proteins, comparisons using 2-DE of extracted proteins from Human Brain
      Frontal Cortex with SB constituents (7M Urea, 2M Thiourea and 100mM DTT) were
      made, using different detergent compositions in the buffer. SB preparations in
      combination with CHAPS and ASB-14 as well as with ASB-16 (reported for the first
      time in 2-DE experiments) have been tested. Our results confirm that the most
      efficient solubilizing solution for 2-DE analysis of cytosolic and membrane Human
      Brain Proteins is SB combined with 4% CHAPS and 2% ASB-14.

PMID- 17556487
TI  - Utility of the WHO Ten Questions Screen for disability detection in a rural
      community the North Indian experience.
AB  - The utility of the WHO Ten Questions Screen (TQS) was studied in a rural
      community of North India. The study was done in three villages, in two phases. In
      phase 1, the TQS was administered to parents of children aged between 2 and 9
      years, during a house-to-house survey. In phase 2, all children screened positive
      and a random sample of 110 screened negative were clinically evaluated in detail.
      The total population of the three villages was 5830 with 1763 children aged
      between 2 and 9 years. Seventy-six children were positive on the TQS, of these,
      38 were found to have significant disability, 18 had protein energy malnutrition
      and 19 were found normal on clinical evaluation. All the 110 screen-negative
      children were normal. Significantly larger numbers of boys were positive on TQS
      as compared to girls [Odd Ratio (OR) 1.5]. The sensitivity of the TQS for
      significant disability was 100%; the positive predictive value was 50% and was
      higher for boys than for girls. Of the 50% children classified as false positive
      23% had mild delays due to malnutrition. The estimated prevalence of disability
      was 16/1000. The TQS was found to be a sensitive tool for detection of
      significant disabilities among children 2-9 years of age. The low-positive
      predictive value would lead to over referrals but a large number of these
      children would benefit from medical attention.

PMID- 17556488
TI  - The pattern and early diagnostic value of Doppler ultrasound for neonatal hypoxic
      ischemic encephalopathy.
AB  - This article investigates the value of early diagnosis and prognostic evaluation
      of Doppler ultrasound for neonatal hypoxic-ischemic encephalopathy (HIE). Study
      population included 40 term neonates with HIE and 30 healthy controls. Color
      Doppler ultrasound was performed at the bedside within 24 h after birth. The
      transducer was placed on the temporal fontanelle to detect the hemodynamic
      parameters of bilateral middle cerebral arteries. The results showed that infants
      with HIE had significant cerebral hemodynamic disturbance. The cerebral blood
      flow velocity decreased or increased markedly as resistive index (RI) decreased
      or increased markedly, which usually suggested the diagnosis of HIE, RI < 0.50 or
      RI > 0.90 usually occurred in severe patients, while RI > 1.0 would be associated
      with later brain death. So we believe that using Pulsed Doppler ultrasound to
      monitor the changes of cerebral hemodynamics can be used for the early diagnosis
      of HIE and help us to distinguish the grades of HIE.

PMID- 17556489
TI  - Risk factors associated with stillbirth in Thai Nguyen province, Vietnam.
AB  - We investigated risk factors associated with stillbirths using personal
      interviews and medical records abstraction in a hospital-based case-control study
      in Thai Nguyen Province, Vietnam. There were 47 stillbirth cases and 365 controls
      in this study. Maternal education (< or =12 years) (Odds Ratio, OR = 3.07; 95% CI
      = 1.19-7.96), from rural communities (OR = 2.42; 95% CI = 1.16-5.03), primiparous
      (OR = 3.83; 95% CI = 1.10-13.40) and lack of prenatal care vitamins (OR = 2.56;
      95% CI = 1.25-5.23) were statistically significant risk factors associated with
      stillbirth in an age-adjusted multivariable model. Our findings suggest that
      improved maternal health education and care in all communities may reduce the
      burden of fetal loss in this province.

PMID- 17556490
TI  - Simultaneous determination of the accuracy and precision of closed-circuit
      cardiac output rebreathing techniques.
AB  - Foreign and soluble gas rebreathing methods are attractive for determining
      cardiac output (Q(c)) because they incur less risk than traditional invasive
      methods such as direct Fick and thermodilution. We compared simultaneously
      obtained Q(c) measurements during rest and exercise to assess the accuracy and
      precision of several rebreathing methods. Q(c) measurements were obtained during
      rest (supine and standing) and stationary cycling (submaximal and maximal) in 13
      men and 1 woman (age: 24 +/- 7 yr; height: 178 +/- 5 cm; weight: 78 +/- 13 kg;
      Vo(2max): 45.1 +/- 9.4 ml.kg(-1).min(-1); mean +/- SD) using one-N(2)O, four
      C(2)H(2), one-CO(2) (single-step) rebreathing technique, and two criterion
      methods (direct Fick and thermodilution). CO(2) rebreathing overestimated Q(c)
      compared with the criterion methods (supine: 8.1 +/- 2.0 vs. 6.4 +/- 1.6 and 7.2
      +/- 1.2 l/min, respectively; maximal exercise: 27.0 +/- 6.0 vs. 24.0 +/- 3.9 and
      23.3 +/- 3.8 l/min). C(2)H(2) and N(2)O rebreathing techniques tended to
      underestimate Q(c) (range: 6.6-7.3 l/min for supine rest; range: 16.0-19.1 l/min
      for maximal exercise). Bartlett's test indicated variance heterogeneity among the
      methods (P < 0.05), where CO(2) rebreathing consistently demonstrated larger
      variance. At rest, most means from the noninvasive techniques were +/-10% of
      direct Fick and thermodilution. During exercise, all methods fell outside the +/
      10% range, except for CO(2) rebreathing. Thus the CO(2) rebreathing method was
      accurate over a wider range (rest through maximal exercise), but was less
      precise. We conclude that foreign gas rebreathing can provide reasonable Q(c)
      estimates with fewer repeat trials during resting conditions. During exercise,
      these methods remain precise but tend to underestimate Q(c). Single-step CO(2)
      rebreathing may be successfully employed over a wider range but with more
      measurements needed to overcome the larger variability.

PMID- 17556491
TI  - The role of CXCR2 in systemic neovascularization of the mouse lung.
AB  - We previously showed increased expression of the ELR+, CXC chemokines in the lung
      after left pulmonary artery obstruction. These chemokines have been shown in
      other systems to bind their G protein-coupled receptor, CXCR(2), and promote
      systemic endothelial cell proliferation, migration, and capillary tube formation.
      In the present study, we blocked CXCR(2) in vivo using a neutralizing antibody
      and also studied mice that were homozygous null for CXCR(2). To estimate the
      extent of neovascularization in this model, we measured systemic blood flow to
      the left lung 14 days after left pulmonary artery ligation (LPAL). We found blood
      flow significantly reduced (67% decrease) with neutralizing antibody treatment
      compared with controls. However, blood flow was not altered in the CXCR(2)
      deficient mice compared with wild-type controls after LPAL. To test for ligand
      availability, we measured macrophage inflammatory protein (MIP)-2 in lung
      homogenates after LPAL, because this is the predominant CXC chemokine previously
      shown to be increased after LPAL (22). MIP-2 protein was two- to fourfold higher
      in the left lung relative to the right lung in all treatment groups 4 h after
      LPAL and this increase did not differ among groups. We speculate that the CXCR(2)
      deficient mice have compensatory mechanisms that mitigate their lack of gene
      expression and conclude that CXCR(2) contributes to chemokine-induced systemic
      angiogenesis after pulmonary artery obstruction.

PMID- 17556492
TI  - Perspectives in innate and acquired cardioprotection: cardioprotection acquired
      through exercise.
AB  - Emerging evidence indicates that exercise training can provide significant
      protection against myocardial ischemia-reperfusion injury. In this brief review,
      we provide a synthesis of current literature in the field and summarize the
      findings to date. Our intent is to identify the unique elements of
      cardioprotection acquired by exercise, and to illustrate what distinguishes this
      physiological acquisition of cardioprotection from all other known types of
      acquired cardioprotection. Finally, we point to future directions for research in
      this exciting area.

PMID- 17556493
TI  - Enhanced endothelin-1-mediated leg vascular tone in healthy older subjects.
AB  - Advanced age is associated with a decreased leg blood flow and reduced physical
      activity. Endothelin (ET-1), a powerful vasoconstrictor, may play a role in the
      increased leg vascular tone in older men. objectives: to assess the ET-1-mediated
      vascular tone in the legs of healthy sedentary older men, both before and after 8
      wk of exercise training. methods: in 8 younger subjects (19-50 yr) and 8 older
      men (67-76 yr), bilateral leg blood flow was measured using venous occlusion
      plethysmography before and after antagonizing ET-1 (using selective ET(A/B)
      receptor antagonists). In older men, reversibility of the observations was
      assessed after 8 wk of cycling. results: ET-receptor inhibition increased leg
      blood flow significantly more in older men compared with younger individuals (29
      +/- 9% and 10 +/- 4%, respectively, P < 0.05). Eight-week cycling training
      increased baseline blood flow in older men. The blood flow response to ET
      receptor inhibition in older men was not affected by the training program (25 +/-
      8%, P > 0.05 for comparison with pretraining). The flow ratio (blood flows
      infused leg/noninfused leg) decreased significantly by training from 26 +/- 8% to
      7+3% (P < 0.05). CONCLUSION: the increased baseline vascular tone in aging is at
      least in part mediated by the endothelin. Eight-weeks cycling training in older
      sedentary men decreased leg vascular tone and seems to partly decrease the ET-1
      mediated vascular tone.

PMID- 17556494
TI  - Linear acceleration-evoked cardiovascular responses in awake rats.
AB  - It has been well documented that vestibular-mediated cardiovascular regulation
      plays an important role in maintaining stable blood pressure (BP) during postural
      changes. But the underlying neural mechanisms remain to be elucidated. In
      particular, because the vestibular stimulation employed in previous animal
      studies activated both semicircular canals and otolith organs, the contributions
      of the otolith system has not been studied selectively. The goal of the present
      study was to characterize cardiovascular responses to natural otolith stimulation
      in awake rats that were subjected to pure linear motion. In any of the four
      directions tested, transient linear motion produced a short-latency (
      approximately 520 ms) increase in mean BP with a peak of 8.27 +/- 0.66 mmHg and
      was followed by a decrease in BP. There was an initial small biphasic response in
      heart rate (HR) that was followed by a longer duration increase. The short
      latency increase in BP was absent in rats that were pentobarbital sodium
      anesthetized or that were labyrinthectomized bilaterally, but it was unaffected
      by baroreceptor denervation, indicating that it was of otolith origin. The
      increase in BP was linear acceleration intensity dependent and was not affected
      by absence of visual cues. Furthermore, the BP response was attenuated by
      inactivation of the medial and inferior vestibular nuclei by microinjections of
      muscimol, indicating that the otolith-driven cardiovascular responses are
      mediated by the neurons in these areas. These results not only demonstrate the
      otolith specific influences on the cardiovascular system but also they establish
      the first rodent model for examining the neural mechanisms underlying the otolith
      mediated cardiovascular regulation.

PMID- 17556495
TI  - Limb-specific differences in flow-mediated dilation: the role of shear rate.
AB  - We sought to examine flow-mediated vasodilation (FMD) in both the arm [brachial
      artery (BA)] and lower leg [popliteal artery (PA)] of 12 young, healthy subjects.
      Vessel diameter, blood velocity, and calculated shear rate were determined with
      ultrasound Doppler following a suprasystolic cuff occlusion (5 min) in both the
      BA and PA and an additional reduced occlusion period (30-120 s) in the BA to more
      closely equate the shear stimulus observed in the PA. The BA revealed a smaller
      diameter and larger postischemic cumulative blood velocity [area under curve
      (AUC)] than the PA, a combination that resulted in an elevated postcuff
      cumulative shear rate (AUC) in the BA (BA: 25,419 +/- 2,896 s(-1).s, PA 8,089 +/-
      1,048 s(-1).s; P < 0.05). Thus, when expressed in traditional terms, there was a
      tendency for the BA to have a greater FMD than the PA (6.5 +/- 1.0 and 4.5 +/-
      0.8%, respectively; P = 0.1). However, when shear rate was experimentally matched
      (PA: 4.5 +/- 0.8%; BA: -0.4 +/- 0.4%) or mathematically normalized (PA: 6.8 x 10(
      4) +/- 1.6 x 10(-4)%Delta/s(-1).s; BA: 2.5 x 10(-4) +/- 0.4 x 10(-4)%Delta/s(
      1).s), the PA revealed a greater FMD per unit of shear rate than the BA (P <
      0.05). These data highlight the importance of assessing the shear stimulus to
      which each vessel is exposed and reveal limb-specific differences in flow
      mediated dilation.

PMID- 17556496
TI  - The effects of nightly normobaric hypoxia and high intensity training under
      intermittent normobaric hypoxia on running economy and hemoglobin mass.
AB  - We investigated the effects of nightly intermittent exposure to hypoxia and of
      training during intermittent hypoxia on both erythropoiesis and running economy
      (RE), which is indicated by the oxygen cost during running at submaximal speeds.
      Twenty-five college long- and middle- distance runners [maximal oxygen uptake
      (Vo(2max)) 60.3 +/- 4.7 ml x kg(-1) x min(-1)] were randomly assigned to one of
      three groups: hypoxic residential group (HypR, 11 h/night at 3,000 m simulated
      altitude), hypoxic training group (HypT), or control group (Con), for an
      intervention of 29 nights. All subjects trained in Tokyo (altitude of 60 m) but
      HypT had additional high-intensity treadmill running for 30 min at 3,000 m
      simulated altitude on 12 days during the night intervention. Vo(2) was measured
      at standing rest during four submaximal speeds (12, 14, 16, and 18 km/h) and
      during a maximal stage to volitional exhaustion on a treadmill. Total hemoglobin
      mass (THb) was measured by carbon monoxide rebreathing. There were no significant
      changes in Vo(2max), THb, and the time to exhaustion in all three groups after
      the intervention. Nevertheless, HypR showed approximately 5% improvement of RE in
      normoxia (P < 0.01) after the intervention, reflected by reduced Vo(2) at 18 km/h
      and the decreased regression slope fitted to Vo(2) measured during rest position
      and the four submaximal speeds (P < 0.05), whereas no significant corresponding
      changes were found in HypT and Con. We concluded that our dose of intermittent
      hypoxia (3,000 m for approximately 11 h/night for 29 nights) was insufficient to
      enhance erythropoiesis or Vo(2max), but improved the RE at race speed of college
      runners.

PMID- 17556497
TI  - Effects of glossopharyngeal insufflation on cardiac function: an
      echocardiographic study in elite breath-hold divers.
AB  - Glossopharyngeal insufflation (GI), a technique used by breath-hold divers to
      increase lung volume and augment diving depth and duration, is associated with
      untoward hemodynamic consequences. To study the cardiac effects of GI, we
      performed transthoracic echocardiography, using the subcostal window, in five
      elite breath-hold divers at rest and during GI. During GI, heart rate increased
      in all divers (mean of 53 beats/min to a mean of 100 beats/min), and blood
      pressure fell dramatically (mean systolic, 112 to 52 mmHg; mean diastolic, 75
      mmHg to nondetectable). GI induced a 46% decrease in mean left ventricular end
      diastolic area, 70% decrease in left ventricular end-diastolic volume, 49%
      increase in mean right ventricular end-diastolic area, and 160% increase in mean
      right ventricular end-diastolic volume. GI also induced biventricular systolic
      dysfunction; left ventricular ejection fraction decreased from 0.60 to a mean of
      0.30 (P = 0.012); right ventricular ejection fraction, from 0.75 to a mean of
      0.39 (P < 0.001). Wall motion of both ventricles became significantly abnormal
      during GI; the most prominent left ventricular abnormalities involved hypokinesis
      or dyskinesis of the interventricular septum, while right ventricular wall motion
      abnormalities involved all visible segments. In two divers, the inferior vena
      cava dilated with the appearance of spontaneous contrast during GI, signaling
      increased right atrial pressure and central venous stasis. Hypotension during GI
      is associated with acute biventricular systolic dysfunction. The
      echocardiographic pattern of right ventricular systolic dysfunction is consistent
      with acute pressure overload, whereas concurrent left ventricular systolic
      dysfunction is likely due to ventricular interdependence.

PMID- 17556498
TI  - Short-term intermittent hypoxia enhances sympathetic responses to continuous
      hypoxia in humans.
AB  - Short-term intermittent hypoxia leads to sustained sympathetic activation and a
      small increase in blood pressure in healthy humans. Because obstructive sleep
      apnea, a condition associated with intermittent hypoxia, is accompanied by
      elevated sympathetic activity and enhanced sympathetic chemoreflex responses to
      acute hypoxia, we sought to determine whether intermittent hypoxia also enhances
      chemoreflex activity in healthy humans. To this end, we measured the responses of
      muscle sympathetic nerve activity (MSNA, peroneal microneurography) to arterial
      chemoreflex stimulation and deactivation before and following exposure to a
      paradigm of repetitive hypoxic apnea (20 s/min for 30 min; O(2) saturation nadir
      81.4 +/- 0.9%). Compared with baseline, repetitive hypoxic apnea increased MSNA
      from 113 +/- 11 to 159 +/- 21 units/min (P = 0.001) and mean blood pressure from
      92.1 +/- 2.9 to 95.5 +/- 2.9 mmHg (P = 0.01; n = 19). Furthermore, compared with
      before, following intermittent hypoxia the MSNA (units/min) responses to acute
      hypoxia [fraction of inspired O(2) (Fi(O(2))) 0.1, for 5 min] were enhanced (pre-
      vs. post-intermittent hypoxia: +16 +/- 4 vs. +49 +/- 10%; P = 0.02; n = 11),
      whereas the responses to hyperoxia (Fi(O(2)) 0.5, for 5 min) were not changed
      significantly (P = NS; n = 8). Thus 30 min of intermittent hypoxia is capable of
      increasing sympathetic activity and sensitizing the sympathetic reflex responses
      to hypoxia in normal humans. Enhanced sympathetic chemoreflex activity induced by
      intermittent hypoxia may contribute to altered neurocirculatory control and
      adverse cardiovascular consequences in sleep apnea.

PMID- 17556499
TI  - Severe hemodilutional anemia increases cerebral tissue injury following acute
      neurotrauma.
AB  - Anemia may worsen neurological outcomes following traumatic brain injury (TBI) by
      undefined mechanisms. We hypothesized that hemodilutional anemia accentuates
      hypoxic cerebral injury following TBI. Anesthetized rats underwent unilateral TBI
      or sham injury (n > or = 7). Target hemoglobin concentrations between 50 and 70
      g/l were achieved by exchanging 40-50% of the blood volume (1:1) with
      pentastarch. The effect of TBI, anemia, and TBI-anemia was assessed by measuring
      brain tissue oxygen tension (Pbr(O(2))), regional cerebral blood flow (rCBF),
      jugular venous oxygen saturation (Sjv(O(2))), cerebral contusion area, and
      nuclear staining for programmed cell death. Baseline postinjury Pbr(O(2)) values
      in the TBI and TBI-anemia groups (9.3 +/- 1.3 and 11.3 +/- 4.1 Torr,
      respectively) were lower than the uninjured controls (18.2 +/- 5.2 Torr, P < 0.05
      for both). Hemodilution caused a further reduction in Pbr(O(2)) in the TBI-anemia
      group relative to the TBI group without anemia (7.8 +/- 2.7 vs. 14.8 +/- 3.9
      Torr, P < 0.05). The rCBF remained stable after TBI and increased comparably
      after hemodilution in both anemia and TBI-anemia groups. The Sjv(O(2)) was
      elevated after TBI (87.4 +/- 8.9%, P < 0.05) and increased further following
      hemodilution (95.0 +/- 1.6%, P < 0.05). Cerebral contusion area and nuclear
      counts for programmed cell death were increased following TBI-anemia (4.1 +/- 3.0
      mm(2) and 686 +/- 192, respectively) relative to TBI alone (1.3 +/- 0.3 mm(2) and
      404 +/- 133, respectively, P < 0.05 for both). Hemodilutional anemia reduced
      cerebral Pbr(O(2)) and oxygen extraction and increased cell death following TBI.
      These results support our hypothesis that acute anemia accentuated hypoxic
      cerebral injury after neurotrauma.

PMID- 17556500
TI  - Effect of denervation on ATP consumption rate of diaphragm muscle fibers.
AB  - Denervation (DNV) of rat diaphragm muscle (DIAm) decreases myosin heavy chain
      (MHC) content in fibers expressing MHC(2X) isoform but not in fibers expressing
      MHC(slow) and MHC(2A). Since MHC is the site of ATP hydrolysis during muscle
      contraction, we hypothesized that ATP consumption rate during maximum isometric
      activation (ATP(iso)) is reduced following unilateral DIAm DNV and that this
      effect is most pronounced in fibers expressing MHC(2X). In single-type
      identified, permeabilized DIAm fibers, ATP(iso) was measured using NADH-linked
      fluorometry. The maximum velocity of the actomyosin ATPase reaction (V(max)
      ATPase) was determined using quantitative histochemistry. The effect of DNV on
      maximum unloaded shortening velocity (V(o)) and cross-bridge cycling rate
      [estimated from the rate constant for force redevelopment (k(TR)) following quick
      release and restretch] was also examined. Two weeks after DNV, ATP(iso) was
      significantly reduced in fibers expressing MHC(2X), but unaffected in fibers
      expressing MHC(slow) and MHC(2A). This effect of DNV on fibers expressing MHC(2X)
      persisted even after normalization for DNV-induced reduction in MHC content. With
      DNV, V(o) and k(TR) were slowed in fibers expressing MHC(2X), consistent with the
      effect on ATP(iso). The difference between V(max) ATPase and ATP(iso) reflects
      reserve capacity for ATP consumption, which was reduced across all fibers
      following DNV; however, this effect was most pronounced in fibers expressing
      MHC(2X). DNV-induced reductions in ATP(iso) and V(max) ATPase of fibers
      expressing MHC(2X) reflect the underlying decrease in MHC content, while
      reduction in ATP(iso) also reflects a slowing of cross-bridge cycling rate.

PMID- 17556501
TI  - How hot is the human body?

PMID- 17556502
TI  - The p160 steroid receptor coactivator 2, SRC-2, regulates murine endometrial
      function and regulates progesterone-independent and -dependent gene expression.
AB  - The role of the p160 steroid receptor coactivator 2 (SRC-2) in the regulation of
      uterine function and progesterone (P4) signaling was investigated by determining
      the expression pattern of SRC-2 in the murine uterus during pregnancy and the
      impact of SRC-2 ablation on uterine function and global uterine gene expression
      in response to progesterone. SRC-2 is expressed in the endometrial luminal and
      glandular epithelium from pregnancy d 0.5. SRC-2 is then expressed in the
      endometrial stroma on pregnancy d 2.5-3.5. Once the embryo is implanted, SRC-2 is
      expressed in the endometrial stromal cells in the secondary decidual zone. This
      compartmental expression of SRC-2 can be mimicked by treatment of ovariectomized
      mice with estrogen and P4. Ablation of SRC-2 in the uterus resulted in a
      significant reduction in the ability of the uterus to undergo a hormonally
      induced decidual reaction. Microarray analysis of RNA from uteri of wild-type and
      SRC-2(-/-) mice treated with vehicle or P4 showed that SRC-2 was involved in the
      ability of progesterone to repress specific genes. This microarray analysis also
      revealed that the uteri of SRC-2(-/-) mice showed alterations in genes involved
      in estrogen receptor, Wnt, and bone morphogenetic protein signaling. This
      analysis indicates that SRC-2 regulates uterine function by modulating the
      regulation of developmentally important signaling molecules and the ability of P4
      to repress specific genes.

PMID- 17556503
TI  - High rates of sexually transmitted infections in HIV positive homosexual men:
      data from two community based cohorts.
AB  - BACKGROUND/OBJECTIVES: Higher levels of sexual risk behaviours have been reported
      in HIV positive than in HIV negative homosexual men. In clinic based studies,
      higher rates of sexually transmitted infections (STIs) have also been reported.
      We compared rates of common STIs between HIV positive and HIV negative homosexual
      men from two ongoing community based cohort studies in Sydney, Australia.
      METHODS: Participants in the two cohorts were recruited using similar community
      based strategies. They were interviewed face to face annually after enrollment.
      Comprehensive sexual health screening, including hepatitis A and B, syphilis,
      gonorrhoea, and chlamydia (in urethra and anus) was offered to participants in
      both cohorts. RESULTS: In participants in the HIV positive cohort, 75% were
      hepatitis A seropositive, 56% had serological evidence of previous or current
      hepatitis B infection, and 24% had evidence of vaccination against hepatitis B
      infection. 19% of men tested positive for syphilis and 4% had evidence of recent
      infections. Compared with men in the HIV negative cohort, after adjustment for
      age, HIV positive participants had significantly higher prevalence of previous or
      current hepatitis B infection, syphilis, and anal gonorrhoea. CONCLUSION: This
      finding supports the need for frequent STI testing in HIV positive men to prevent
      morbidity and to decrease the risk of ongoing HIV transmission.

PMID- 17556504
TI  - Genome-wide gene expression profiling reveals conserved and novel molecular
      functions of the stigma in rice.
AB  - In angiosperms, the stigma provides initial nutrients and guidance cues for
      pollen grain germination and tube growth. However, little is known about the
      genes that regulate these processes in rice (Oryza sativa). Here, we generate
      rice stigma-specific or -preferential gene expression profiles through comparing
      genome-wide expression patterns of hand-dissected, unpollinated stigma at
      anthesis with seven tissues, including seedling shoot, seedling root, mature
      anther, ovary at anthesis, seeds 5 d after pollination, 10-d-old embryo, 10-d-old
      endosperm, and suspension-cultured cells by using both 57 K Affymetrix rice whole
      genome array and 10 K rice cDNA microarray. A high reproducibility of the
      microarray results was detected between the two different technology platforms.
      In total, we identified 548 genes to be expressed specifically or predominantly
      in the stigma papillar cells of rice. Real-time quantitative reverse
      transcription-polymerase chain reaction analysis of 34 selected genes all
      confirmed their stigma-specific expression. The expression of five selected genes
      was further validated by RNA in situ hybridization. Gene Ontology analysis shows
      that several auxin-signaling components, transcription, and stress-related genes
      are significantly overrepresented in the rice stigma gene set. Interestingly,
      most of them also share several cis-regulatory elements with known stress
      responsive genes, supporting the notion of an overlap of genetic programs
      regulating pollination and stress/defense responses. We also found that genes
      involved in cell wall metabolism and cellular communication appear to be
      conserved in the stigma between rice and Arabidopsis (Arabidopsis thaliana). Our
      results indicate that the stigmas appear to have conserved and novel molecular
      functions between rice and Arabidopsis.

PMID- 17556505
TI  - Double mutants deficient in cytosolic and thylakoid ascorbate peroxidase reveal a
      complex mode of interaction between reactive oxygen species, plant development,
      and response to abiotic stresses.
AB  - Reactive oxygen species (ROS) play a key signaling role in plants and are
      controlled in cells by a complex network of ROS metabolizing enzymes found in
      several different cellular compartments. To study how different ROS signals,
      generated in different cellular compartments, are integrated in cells, we
      generated a double mutant lacking thylakoid ascorbate peroxidase (tylapx) and
      cytosolic ascorbate peroxidase1 (apx1). Our analysis suggests that two different
      signals are generated in plants lacking cytosolic APX1 or tylAPX. The lack of a
      chloroplastic hydrogen peroxide removal enzyme triggers a specific signal in
      cells that results in enhanced tolerance to heat stress, whereas the lack of a
      cytosolic hydrogen peroxide removal enzyme triggers a different signal, which
      results in stunted growth and enhanced sensitivity to oxidative stress. When the
      two signals are coactivated in cells (i.e. tylapx/apx1), a new response is
      detected, suggesting that the integration of the two different signals results in
      a new signal that manifests in late flowering, low protein oxidation during light
      stress, and enhanced accumulation of anthocyanins. Our results demonstrate a high
      degree of plasticity in ROS signaling in Arabidopsis (Arabidopsis thaliana) and
      suggest the existence of redundant pathways for ROS protection that compensate
      for the lack of classical ROS removal enzymes such as cytosolic and chloroplastic
      APXs. Further investigation of the enhanced heat tolerance in plants lacking
      tylAPX, using mutants deficient in chloroplast-to-nuclei retrograde signaling,
      suggests the existence of a chloroplast-generated stress signal that enhances
      basal thermotolerance in plants.

PMID- 17556506
TI  - Leaf maximum photosynthetic rate and venation are linked by hydraulics.
AB  - Leaf veins are almost ubiquitous across the range of terrestrial plant diversity,
      yet their influence on leaf photosynthetic performance remains uncertain. We show
      here that specific physical attributes of the vascular plumbing network are key
      limiters of the hydraulic and photosynthetic proficiency of any leaf. Following
      the logic that leaf veins evolved to bypass inefficient water transport through
      living mesophyll tissue, we examined the hydraulic pathway beyond the distal ends
      of the vein system as a possible limiter of water transport in leaves. We tested
      a mechanistic hypothesis that the length of this final traverse, as water moves
      from veins across the mesophyll to where it evaporates from the leaf, governs the
      hydraulic efficiency and photosynthetic carbon assimilation of any leaf. Sampling
      43 species across the breadth of plant diversity from mosses to flowering plants,
      we found that the post-vein traverse as determined by characters such as vein
      density, leaf thickness, and cell shape, was strongly correlated with the
      hydraulic conductivity and maximum photosynthetic rate of foliage. The shape of
      this correlation provided clear support for the a priori hypothesis that vein
      positioning limits photosynthesis via its influence on leaf hydraulic efficiency.

PMID- 17556507
TI  - Auxin influx activity is associated with Frankia infection during actinorhizal
      nodule formation in Casuarina glauca.
AB  - Plants from the Casuarinaceae family enter symbiosis with the actinomycete
      Frankia leading to the formation of nitrogen-fixing root nodules. We observed
      that application of the auxin influx inhibitor 1-naphtoxyacetic acid perturbs
      actinorhizal nodule formation. This suggests a potential role for auxin influx
      carriers in the infection process. We therefore isolated and characterized
      homologs of the auxin influx carrier (AUX1-LAX) genes in Casuarina glauca. Two
      members of this family were found to share high levels of deduced protein
      sequence identity with Arabidopsis (Arabidopsis thaliana) AUX-LAX proteins.
      Complementation of the Arabidopsis aux1 mutant revealed that one of them is
      functionally equivalent to AUX1 and was named CgAUX1. The spatial and temporal
      expression pattern of CgAUX1 promoter:beta-glucuronidase reporter was analyzed in
      Casuarinaceae. We observed that CgAUX1 was expressed in plant cells infected by
      Frankia throughout the course of actinorhizal nodule formation. Our data suggest
      that auxin plays an important role during plant cell infection in actinorhizal
      symbioses.

PMID- 17556509
TI  - How a plant lectin recognizes high mannose oligosaccharides.
AB  - The crystal structure of Pterocarpus angolensis seed lectin is presented in
      complex with a series of high mannose (Man) oligosaccharides ranging from Man-5
      to Man-9. Despite that several of the nine Man residues of Man-9 have the
      potential to bind in the monosaccharide-binding site, all oligomannoses are bound
      in the same unique way, employing the tetrasaccharide sequence Manalpha(1
      2)Manalpha(1-6)[Manalpha(1-3)]Manalpha(1-. Isothermal titration calorimetry
      titration experiments using Man-5, Man-9, and the Man-9-containing glycoprotein
      soybean (Glycine max) agglutinin as ligands confirm the monovalence of Man-9 and
      show a 4-times higher affinity for Man-9 when it is presented to P. angolensis
      seed lectin in a glycoprotein context.

PMID- 17556508
TI  - Genome-wide analysis of the core DNA replication machinery in the higher plants
      Arabidopsis and rice.
AB  - Core DNA replication proteins mediate the initiation, elongation, and Okazaki
      fragment maturation functions of DNA replication. Although this process is
      generally conserved in eukaryotes, important differences in the molecular
      architecture of the DNA replication machine and the function of individual
      subunits have been reported in various model systems. We have combined genome
      wide bioinformatic analyses of Arabidopsis (Arabidopsis thaliana) and rice (Oryza
      sativa) with published experimental data to provide a comprehensive view of the
      core DNA replication machinery in plants. Many components identified in this
      analysis have not been studied previously in plant systems, including the GINS
      (go ichi ni san) complex (PSF1, PSF2, PSF3, and SLD5), MCM8, MCM9, MCM10, NOC3,
      POLA2, POLA3, POLA4, POLD3, POLD4, and RNASEH2. Our results indicate that the
      core DNA replication machinery from plants is more similar to vertebrates than
      single-celled yeasts (Saccharomyces cerevisiae), suggesting that animal models
      may be more relevant to plant systems. However, we also uncovered some important
      differences between plants and vertebrate machinery. For example, we did not
      identify geminin or RNASEH1 genes in plants. Our analyses also indicate that
      plants may be unique among eukaryotes in that they have multiple copies of
      numerous core DNA replication genes. This finding raises the question of whether
      specialized functions have evolved in some cases. This analysis establishes that
      the core DNA replication machinery is highly conserved across plant species and
      displays many features in common with other eukaryotes and some characteristics
      that are unique to plants.

PMID- 17556510
TI  - Role of the low-molecular-weight subunits PetL, PetG, and PetN in assembly,
      stability, and dimerization of the cytochrome b6f complex in tobacco.
AB  - The cytochrome b(6)f (Cyt b(6)f) complex in flowering plants contains nine
      conserved subunits, of which three, PetG, PetL, and PetN, are bitopic plastid
      encoded low-molecular-weight proteins of largely unknown function. Homoplastomic
      knockout lines of the three genes have been generated in tobacco (Nicotiana
      tabacum 'Petit Havana') to analyze and compare their roles in assembly and
      stability of the complex. Deletion of petG or petN caused a bleached phenotype
      and loss of photosynthetic electron transport and photoautotrophy. Levels of all
      subunits that constitute the Cyt b(6)f complex were faintly detectable,
      indicating that both proteins are essential for the stability of the membrane
      complex. In contrast, DeltapetL plants accumulate about 50% of other Cyt b(6)f
      subunits, appear green, and grow photoautotrophically. However, DeltapetL plants
      show increased light sensitivity as compared to wild type. Assembly studies
      revealed that PetL is primarily required for proper conformation of the Rieske
      protein, leading to stability and formation of dimeric Cyt b(6)f complexes.
      Unlike wild type, phosphorylation levels of the outer antenna of photosystem II
      (PSII) are significantly decreased under state II conditions, although the
      plastoquinone pool is largely reduced in DeltapetL, as revealed by measurements
      of PSI and PSII redox states. This confirms the sensory role of the Cyt b(6)f
      complex in activation of the corresponding kinase. The reduced light-harvesting
      complex II phosphorylation did not affect state transition and association of
      light-harvesting complex II to PSI under state II conditions. Ferredoxin
      dependent plastoquinone reduction, which functions in cyclic electron transport
      around PSI in vivo, was not impaired in DeltapetL.

PMID- 17556511
TI  - STRESS RESPONSE SUPPRESSOR1 and STRESS RESPONSE SUPPRESSOR2, two DEAD-box RNA
      helicases that attenuate Arabidopsis responses to multiple abiotic stresses.
AB  - Two genes encoding Arabidopsis (Arabidopsis thaliana) DEAD-box RNA helicases were
      identified in a functional genomics screen as being down-regulated by multiple
      abiotic stresses. Mutations in either gene caused increased tolerance to salt,
      osmotic, and heat stresses, suggesting that the helicases suppress responses to
      abiotic stress. The genes were therefore designated STRESS RESPONSE SUPPRESSOR1
      (STRS1; At1g31970) and STRS2 (At5g08620). In the strs mutants, salt, osmotic, and
      cold stresses induced enhanced expression of genes encoding the transcriptional
      activators DREB1A/CBF3 and DREB2A and a downstream DREB target gene, RD29A. Under
      heat stress, the strs mutants exhibited enhanced expression of the heat shock
      transcription factor genes, HSF4 and HSF7, and the downstream gene HEAT SHOCK
      PROTEIN101. Germination of mutant seed was hyposensitive to the phytohormone
      abscisic acid (ABA), but mutants showed up-regulated expression of genes encoding
      ABA-dependent stress-responsive transcriptional activators and their downstream
      targets. In wild-type plants, STRS1 and STRS2 expression was rapidly down
      regulated by salt, osmotic, and heat stress, but not cold stress. STRS expression
      was also reduced by ABA, but salt stress led to reduced STRS expression in both
      wild-type and ABA-deficient mutant plants. Taken together, our results suggest
      that STRS1 and STRS2 attenuate the expression of stress-responsive
      transcriptional activators and function in ABA-dependent and ABA-independent
      abiotic stress signaling networks.

PMID- 17556512
TI  - Involvement of a soybean ATP-binding cassette-type transporter in the secretion
      of genistein, a signal flavonoid in legume-Rhizobium symbiosis.
AB  - Legume plants have an ability to fix atmospheric nitrogen into nutrients via
      symbiosis with soil microbes. As the initial event of the symbiosis, legume
      plants secrete flavonoids into the rhizosphere to attract rhizobia. Secretion of
      flavonoids is indispensable for the establishment of symbiotic nitrogen fixation,
      but almost nothing is known about the membrane transport mechanism of flavonoid
      secretion from legume root cells. In this study, we performed biochemical
      analyses to characterize the transport mechanism of flavonoid secretion using
      soybean (Glycine max) in which genistein is a signal flavonoid. Plasma membrane
      vesicles prepared from soybean roots showed clear transport activity of genistein
      in an ATP-dependent manner. This transport activity was inhibited by sodium
      orthovanadate, a typical inhibitor of ATP-binding cassette (ABC) transporters,
      but was hardly affected by various ionophores, such as gramicidin D, nigericin,
      or valinomycin, suggesting involvement of an ABC transporter in the secretion of
      flavonoids from soybean roots. The K(m) and V(max) values of this transport were
      calculated to be 158 mum and 322 pmol mg protein(-1) min(-1), respectively.
      Competition experiments using various flavonoids of both aglycone and glucoside
      varieties suggested that this ABC-type transporter recognizes genistein and
      daidzein, another signaling compound in soybean root exudates, as well as other
      isoflavonoid aglycones as its substrates. Transport activity was constitutive
      regardless of the availability of nitrogen nutrition. This is, to our knowledge,
      the first biochemical characterization of the membrane transport of flavonoid
      secretion from roots.

PMID- 17556513
TI  - Silencing of the major salt-dependent isoform of pectinesterase in tomato alters
      fruit softening.
AB  - Pectinesterase (PE; E.C. 3.1.1.11) is an enzyme responsible for the demethylation
      of galacturonyl residues in high-molecular-weight pectin and is believed to play
      an important role in cell wall metabolism. In this study, Pmeu1, a ubiquitously
      expressed PE gene, has been characterized by antisense suppression in tomato
      (Solanum lycopersicum). Transgenic tomato plants showed reduced PE activity
      levels in both green fruit and leaf tissue to around 65% and 25% of that found in
      wild-type plants, respectively. Pmeu1 was observed to encode a salt-dependent PE
      isoform that correlated with PE1 as previously described in fruit tissue.
      Silencing of Pmeu1 did not result in any detectable phenotype within the leaf
      tissue despite the gene product representing the major isoform in this tissue. In
      comparison, silencing in fruit resulted in an enhancement to the rate of
      softening during ripening. The role of PMEU1 in fruit ripening is discussed.

PMID- 17556514
TI  - Exclusion of Na+ via sodium ATPase (PpENA1) ensures normal growth of
      Physcomitrella patens under moderate salt stress.
AB  - The bryophyte Physcomitrella patens is unlike any other plant identified to date
      in that it possesses a gene that encodes an ENA-type Na(+)-ATPase. To complement
      previous work in yeast (Saccharomyces cerevisiae), we determined the importance
      of having a Na(+)-ATPase in planta by conducting physiological analyses of PpENA1
      in Physcomitrella. Expression studies showed that PpENA1 is up-regulated by NaCl
      and, to a lesser degree, by osmotic stress. Maximal induction is obtained after 8
      h at 60 mm NaCl or above. No other abiotic stress tested led to significant
      increases in PpENA1 expression. In the gametophyte, strong expression was
      confined to the rhizoids, stem, and the basal part of the leaf. In the
      protonemata, expression was ubiquitous with a few filaments showing stronger
      expression. At 100 mm NaCl, wild-type plants were able to maintain a higher K(+)
      to-Na(+) ratio than the PpENA1 (ena1) knockout gene, but at higher NaCl
      concentrations no difference was observed. Although no difference in chlorophyll
      content was observed between ena1 and wild type at 100 mm NaCl, the impaired
      Na(+) exclusion in ena1 plants led to an approximately 40% decrease in growth.

PMID- 17556515
TI  - A genomics approach reveals that aroma production in apple is controlled by
      ethylene predominantly at the final step in each biosynthetic pathway.
AB  - Ethylene is the major effector of ripening in many fleshy fruits. In apples
      (Malus x domestica) the addition of ethylene causes a climacteric burst of
      respiration, an increase in aroma, and softening of the flesh. We have generated
      a transgenic line of 'Royal Gala' apple that produces no detectable levels of
      ethylene using antisense ACC OXIDASE, resulting in apples with no ethylene
      induced ripening attributes. In response to external ethylene these antisense
      fruits undergo a normal climacteric burst and produced increasing concentrations
      of ester, polypropanoid, and terpene volatile compounds over an 8-d period. A
      total of 186 candidate genes that might be involved in the production of these
      compounds were mined from expressed sequence tags databases and full sequence
      obtained. Expression patterns of 179 of these were assessed using a 15,720
      oligonucleotide apple microarray. Based on sequence similarity and gene
      expression patterns we identified 17 candidate genes that are likely to be
      ethylene control points for aroma production in apple. While many of the
      biosynthetic steps in these pathways were represented by gene families containing
      two or more genes, expression patterns revealed that only a single member is
      typically regulated by ethylene. Only certain points within the aroma
      biosynthesis pathways were regulated by ethylene. Often the first step, and in
      all pathways the last steps, contained enzymes that were ethylene regulated. This
      analysis suggests that the initial and final enzymatic steps with the
      biosynthetic pathways are important transcriptional regulation points for aroma
      production in apple.

PMID- 17556516
TI  - Legume biology: sequence to seeds.

PMID- 17556517
TI  - Legume transcription factors: global regulators of plant development and response
      to the environment.

PMID- 17556518
TI  - Translocation in legumes: assimilates, nutrients, and signaling molecules.

PMID- 17556520
TI  - Legume evolution: where do nodules and mycorrhizas fit in?

PMID- 17556521
TI  - Recent advances in legume-microbe interactions: recognition, defense response,
      and symbiosis from a genomic perspective.

PMID- 17556522
TI  - Genome sequencing and genome resources in model legumes.

PMID- 17556523
TI  - Genomic and genetic control of phosphate stress in legumes.

PMID- 17556519
TI  - Using genomics to study legume seed development.

PMID- 17556524
TI  - Nutrient sharing between symbionts.

PMID- 17556526
TI  - Pediatric development of glucuronidation: the ontogeny of hepatic UGT1A4.
AB  - This article reports on the development of UDP-glucuronosyltransferase (UGT)
      enzyme activity in pediatric livers. The substrates 4-methylumbelliferone (4MU)
      and trifluoperazine (TFP) were used as probes for general glucuronidation and
      specific UGT1A4 activity, respectively. The activity of hepatic beta
      glucuronidase enzymes was also determined so as to investigate the balance
      between glucuronide clearance and systemic recirculation. UGT activity toward 4MU
      reached maximum levels by 20 months of age, whereas the activity of beta
      glucuronidase was highest in the neonatal liver and decreased to steady-state
      adult levels by 4 months. The average V(max) and K(m) values for UGT1A4 in
      pediatric samples were 151.9 +/- 63.5 pmol/min/mg protein and 14.4 +/- 9.6 muM,
      respectively. Average V(max) was understandably low because of developmental
      dynamics, but K(m) was similar to values reported elsewhere. When a constant rate
      of enzyme development is assumed, maximum activity of UGT1A4 occurs at 1.4 years
      of age. When the intrinsic hepatic clearance of TFP was scaled with an allometric
      model, hepatic clearance of TFP by UGT1A4 did not reach maximum levels until 18.9
      years of age and scaled results underestimated reported in vivo clearances in
      adult males. No significant differences in UGT activities or hepatic clearance
      were observed with gender or ethnicity. The developmental dynamics of most drug
      metabolizing enzymes are unknown, and this article contains, to our knowledge,
      the first description of the development of a single UGT isoform in childhood.
      Ultimately, work such as this is important for predicting drug responses and for
      developing and evaluating new medications in children.

PMID- 17556525
TI  - Genomes of the symbiotic nitrogen-fixing bacteria of legumes.

PMID- 17556527
TI  - Influence of anthropometry on race performance in extreme endurance triathletes:
      World Challenge Deca Iron Triathlon 2006.
AB  - OBJECTIVE: To investigate the influence of anthropometric variables on race
      performance in ultra-endurance triathletes in an ultra-triathlon. DESIGN:
      Descriptive field study. SETTING: The "World Challenge Deca Iron Triathlon 2006"
      in Monterrey, Mexico, in which everyday for 10 consecutive days athletes had to
      perform the distance of one Ironman triathlon of 3.8 km swimming, 180 km cycling
      and 42.195 km running. SUBJECTS: Eight male ultra-endurance athletes (mean (SD)
      age 40.6 (10.7) years, weight 76.4 (8.4) kg, height 175 (4) cm and body mass
      index (BMI) 24.7 (2.2) kg/m2). INTERVENTIONS: None. MAIN OUTCOME MEASURES: Direct
      measurement of body mass, height, leg length, skinfold thicknesses, limb
      circumference and calculation of BMI, skeletal muscle mass (SM), percentage SM
      (%SM) and percentage body fat (%BF) in order to correlate measured and calculated
      anthropometric variables with race performance. RESULTS: Race time was not
      significantly (p>0.05) influenced by the directly measured variables, height, leg
      length, body mass, average skinfold thicknesses, or circumference of thigh, calf
      or upper arm. Furthermore, no significant (p>0.05) correlation was observed
      between race time and the calculated variables, BMI, %SM and %BF. CONCLUSIONS: In
      a multistage ultra-triathlon over 10 Ironman triathlon distances in 10
      consecutive days, there was no effect of body mass, height, leg length, skinfold
      thicknesses, limb circumference, BMI, %SM or %BF on race performance in the only
      eight finishers.

PMID- 17556528
TI  - Differing patterns of selection in alternative and constitutive splice sites.
AB  - In addition to allowing identification of putative functional elements as regions
      having reduced substitution rates, comparison of genome sequences can also
      provide insights into these elements at the nucleotide level, by indicating the
      pattern of tolerated substitutions. We created data sets of orthologous
      alternative and constitutive splice sites in mouse, rat, and human and analyzed
      the substitutions occurring within them. Our results illuminate differences
      between alternative and constitutive sites and, in particular, strongly support
      the idea that alternative sites are under selection to be weak.

PMID- 17556529
TI  - Genome-wide comparative analysis of copia retrotransposons in Triticeae, rice,
      and Arabidopsis reveals conserved ancient evolutionary lineages and distinct
      dynamics of individual copia families.
AB  - Although copia retrotransposons are major components of all plant genomes, the
      evolutionary relationships between individual copia families and between elements
      from different plant species are only poorly studied. We used 20 copia families
      from the large-genome plants barley and wheat to identify 46 families of
      homologous copia elements from rice and 22 from Arabidopsis, two plant species
      with much smaller genomes. In total, 599 copia elements were analyzed.
      Phylogenetic analysis showed that copia elements from the four species can be
      classified into six ancient lineages that existed before the divergence of
      monocots and dicots. The six lineages show a surprising degree of conservation in
      sequence organization and other characteristics across species. Additionally, the
      phylogenetic data suggest at least one case of horizontal gene transfer between
      the Arabidopsis and rice lineages. Insertion time estimates for 522 high-copy
      elements showed that retrotransposons from rice were active at different times in
      waves of activity lasting 0.5-2 million years, depending on the family, whereas
      elements from wheat and barley had longer periods of activity. We estimated that
      half of the rice copia elements are truncated or otherwise rearranged after
      approximately 790,000 yr, which is almost twice the half-life of Arabidopsis
      elements. In contrast, wheat and barley copia elements appear to have a massively
      longer half-life, beyond our ability to estimate from the available data. These
      findings suggest that genome size can be explained by the specific rate of DNA
      removal from the genome and the length of active periods of retrotransposon
      families.

PMID- 17556530
TI  - Activation of the human immunodeficiency virus type I long terminal repeat by 1
      alpha,25-dihydroxyvitamin D3.
AB  - The genetic predisposition of the host and the virus is the most important
      determinant for prediction of the course of human immunodeficiency virus type I
      (HIV-1) viral infection and acquired immune deficiency syndrome (AIDS)
      progression. Transcription from the HIV-1 long terminal repeat (LTR) is a crucial
      step for viral replication. Here, we describe a stimulatory role of the vitamin D
      receptor (VDR) on HIV-1 LTR transactivation. Transient transfections reveal that
      VDR activates the LTR in HeLa, U937, and Cos-1 cells in a ligand-dependent
      manner. 1alpha,25-Dihydroxyvitamin D3 (vitD3) promotes activation of a minimal
      LTR construct (from nucleotides -35 to +89), lacking a previously described
      hormone response element that binds several nuclear receptors. NF-kappaB (nuclear
      factor-kappa B) and Sp1-binding sites, which are responsible for most basal LTR
      activity in HeLa cells, are also dispensable for vitD3-dependent HIV-1
      transcription. Although the tat response element element is not required for VDR
      mediated HIV-1 gene expression, the viral protein Tat acts in a synergistic
      manner with the receptor to stimulate LTR activity. Furthermore, our data also
      show cooperation of the receptor with various cellular coactivators for HIV-1
      transactivation by vitD3. Paradoxically, mutations in the VDR ligand-dependent
      transcriptional activation function-2 that abrogate vitD3-dependent stimulation
      through classical vitamin D response elements, do not reduce vitD3-mediated LTR
      transactivation. Furthermore, point mutations in the DNA-binding domain that
      abolish receptor binding to consensus DNA sequences do not affect ligand
      dependent HIV-1 stimulation. These results show that VDR activates the HIV-1 LTR
      through different mechanisms, including non-classical nuclear receptor
      transcriptional actions that may ensure viral transcription under different
      physiological scenarios.

PMID- 17556531
TI  - Association of estrogen receptor beta with plasma-membrane caveola components:
      implication in control of vitamin D receptor.
AB  - This study was designed to provide a direct demonstration of the importance of
      caveolin-1 in the compartmentalization of estrogen receptor beta (ERbeta) to the
      membrane, thus allowing 7beta-estradiol (E2) to control vitamin D receptor (VDR)
      transcription and expression. Our strategy was to obtain cell lines expressing
      different levels of caveolin-1. To this end, we transfected human embryonic
      kidney 293 cells with a caveolin-1-expressing vector and obtained three cell-line
      variants: one expressing high amounts of caveolin-1 (clone A), one expressing low
      amounts of caveolin-1 (clone B), and one expressing high amounts of the
      nonfunctional P132L caveolin-1 mutant (clone C), and compared these with parental
      (wild-type, WT) cells expressing negligible levels of caveolin-1. In clone A,
      ERbeta colocalized to membrane preparations and E2 treatment induced significant
      ERK 1/2 phosphorylation and enhanced VDR expression. In clones B and C and the
      WT, ERbeta did not localize to membrane preparations and E2 treatment was
      ineffective at inducing VDR upregulation associated with ERK 1/2 phosphorylation.
      Luciferase reporter gene expression assays showed that the human VDR promoter is
      only highly responsive to E2 treatment in clone A, except in the presence of the
      ER-specific inhibitor ICI182 780. Cotransfection of clone A with the VDR promoter
      and several mutants of MAPK kinase (MEK) demonstrated that the constitutively
      active form of MEK significantly increases VDR promoter activation, while the
      catalytically inactive construct is ineffective in this regard. In clone A cells
      transfected with an activation protein-1 (AP-1)-luciferase construct, E2
      significantly upregulated the promoter activity, while ICI182 780 completely
      eliminated this E2-mediated effect. Clone A cells transfected with a VDR promoter
      bearing a targeted mutation towards the AP-1 site showed reduced E2-mediated
      activation of luciferase activity. Taken together, our data confirm the
      importance of caveolin-1 in the association of ERbeta to the membrane caveolae,
      allowing ERK 1/2 phosphorylation and upregulation of VDR.

PMID- 17556532
TI  - Phosphatidylinositol 3-kinase/nuclear factor-kappa B signaling pathway is
      involved in the regulation of IGF-I on Fas-associated death domain-like
      interleukin-1-converting enzyme-inhibitory protein expression in cultured FRTL
      thyroid cells.
AB  - It is known that decreased apoptosis of thyrocytes may be involved in the
      formation of goiters in patients with Graves' disease, and growth factors are
      involved in regulating the size of the thyroid gland. The purpose of our study
      was to investigate mRNA and protein levels of an antiapoptotic protein, namely,
      Fas-associated death domain-like interleukin-1-converting enzyme (FLICE)
      inhibitory protein (FLIP). The results showed that in FRTL thyroid cells,
      treatment with IGF-I upregulated mRNA and protein levels of FLIP in a dose
      dependant manner. While a specific nuclear factor-kappaB (NF-kappaB) inhibitor,
      BAY11-7082, blocked this effect. Further study demonstrated that IGF-I induced
      the DNA-binding activity of NF-kappaB in association with decreased expression of
      the NF-kappaB inhibitory protein IkappaBalpha . These findings implied that IGF-I
      increased FLIP expression by enhancing the activation of NF-kappaB in FRTL
      thyroid cells. Using a specific phosphatidylinositol 3-kinase (PI3K) inhibitor,
      LY294002, we also found that PI3K was involved in the pathway by which IGF-I
      activated NF-kappaB and increased FLIP expression. When treated with IGF-I and
      LY294002, decreased NF-kappaB DNA binding activity and increased expression of
      IkappaBalpha protein were detected in cultured thyroid cells, which further
      confirmed that NF-kappaB was under the control of the PI3K pathway. Taken
      together, our results suggest that IGF-I regulates the expression of FLIP in FRTL
      cells by activating the PI3K/NF-kappaB cascade.

PMID- 17556533
TI  - Molecular mechanism of bis(maltolato)oxovanadium(IV)-induced insulin signaling in
      3T3-L1 and IM9 cells: impact of dexamethasone.
AB  - The organovanadium compound bis(maltolato)oxovanadium(IV) (BMOV) enhanced the tyr
      phosphorylation of major upstream insulin signaling proteins including the vital
      site-specific phosphorylation of insulin receptor beta (IRbeta) in IM9 and 3T3-L1
      cells in dose- and time-dependent manners more efficiently than insulin.
      Nevertheless, insulin in general had a synergistic impact on those
      phosphorylations in both cell lines, while its presence was obligatory to induce
      Tyr(972)-phosphorylation of IRbeta in IM9 cells at 18-h treatment with BMOV.
      However, prolonged exposure of cells to BMOV caused depletion in IR level and
      using IM9 cells we found that this event was counteracted by insulin, where
      monensin, a monocarboxylic acid ionophore made an additive impact, suggesting
      that a novel mechanism is being involved in the recycling of internalized IR in
      BMOV-treated cells. On the other hand, dexamethasone elevated the IR level in
      both cell lines. However, no correlation was found between the cellular content
      and the degree of phosphorylation of IRbeta in cells receiving combined treatment
      of BMOV, and dexamethasone with short insulin post-exposure. BMOV also induced
      the phosphorylation of Thr(308) and Ser(473) of Akt in both cell lines receiving
      insulin post-treatment, while dexamethasone decreased those phosphorylations.
      However, this activation/deactivation of Akt did not correlate with the
      phosphorylation status of Ser(9) and Ser(259) of glycogen synthase kinase (GSK)
      3beta and Raf respectively. Taken together, it is conceivable that BMOV and/or
      dexamethasone modulate insulin signaling by acting differentially on the
      components of the insulin signaling network. We also consider that the observed
      dexamethasone-mediated modulation of insulin receptor kinase in BMOV-treated 3T3
      L1 cells probably occurs through the activation/deactivation of some mechanism
      which needs further studies for proper characterization.

PMID- 17556534
TI  - The role of G protein-coupled receptor 40 in lipoapoptosis in mouse beta-cell
      line NIT-1.
AB  - Free fatty acids (FFAs) exert divergent effects on beta-cells. Acute exposure to
      FFAs stimulates insulin secretion, whereas chronic exposure impairs beta-cell
      function and induces apoptosis. The G protein-coupled receptor 40 (GPR40) is
      preferentially expressed in beta-cells and is activated by a wide range of FFAs.
      In this study, we used small interfering RNA technology and apoptosis assay in
      mouse beta-cell NIT-1 to address the role of GPR40 in beta-cell lipoapoptosis and
      function. Results showed that palmitate induced beta-cell apoptosis, which was
      not mediated through GPR40, whereas oleate protected NIT-1 cells from palmitate
      induced lipoapoptosis, which was mediated at least in part through GPR40.
      Moreover, by detecting the activation of the phosphatidylinositol 3-kinase and
      MAP kinase (MAPK) pathways, we found that oleate promoted the activation of
      extracellular signal-regulated protein kinase-MAPK pathway mainly via GPR40,
      increased the expression of early growth response gene-1, leading to the anti
      lipoapoptotic effect on NIT-1 cells. It was suggested that GPR40 might be
      implicated in the control of beta-cell mass plasticity and GPR40 probably provide
      a link between obesity and type 2 diabetes.

PMID- 17556535
TI  - The retinol acid receptor B gene is hypermethylated in patients with familial
      partial lipodystrophy.
AB  - Mutations in the LMNA gene cause various phenotypes including partial
      lipodystrophy, muscular dystrophies, and progeroid syndromes. The specific
      mutation position within the LMNA sequence can partially predict the phenotype,
      but the underlying mechanisms for the development of these different phenotypes
      are still unclear. To investigate whether different DNA methylation patterns
      contribute to the development of different phenotypes caused by LMNA mutations,
      we analyzed a panel of ten candidate genes related to fat metabolism, aging, and
      a tendency to different methylation patterns: CSPG2, ESR1, IGF1R, IGFR2, LMNA,
      MLH1, RANBP1, RARB, ZMPSTE24, and TGFBR1. We studied two independent families
      each comprising three individuals affected by familial partial lipodistrophy type
      2 (FPLD2). Affected members in each family carried two different mutations of the
      LMNA gene (R482L and R471G respectively). In addition, we analyzed four progeria
      patients (2xLMNA/C G608G, 1xLMNA/C S143F, and 1xZMPSTE24 IVS9-Ex10) and seven
      healthy adults. The gene encoding retinoic acid receptor B (RARB) showed a higher
      methylation in all six patients with FPLD2 when compared with the progeria
      patients with other LMNA mutations as well as the healthy controls (P<0.05). All
      other investigated genes showed no difference in the methylation patterns between
      the groups. A drug-induced inhibition of the retinol pathway is discussed as the
      key pathway for developing HAART-associated lipodystrophy and our data support a
      possible role of the retinol pathway in the development of lipodystrophy
      phenotypes.

PMID- 17556536
TI  - Constitutively active FOXO1a and a DNA-binding domain mutant exhibit distinct co
      regulatory functions to enhance progesterone receptor A activity.
AB  - FOXO (Forkhead box O1 transcription factors) factors interact with and modify the
      activity of other transcription factors, including nuclear hormone receptors.
      However, not all of the structural domains within the FOXO proteins that mediate
      these functional interactions have been clearly defined. To address this issue,
      we used a constitutively active (nuclear) mutant of FOXO1a (designated FOXOA3)
      and within FOXOA3 made additional mutations to alter the putative nuclear hormone
      interacting domain (NID), minimal activation domain (MAD), DNA-binding domain
      (DBD), and the N terminus. We document that FOXOA3 enhanced the hormone-dependent
      transcriptional activity of liganded progesterone receptors A (PGRA) on a
      glucocorticoid response element-responsive promoter, PGRA on the insulin-like
      growth factor-binding protein 1 promoter, and estrogen receptor alpha on an
      estrogen response element-responsive promoter. The effects of FOXOA3 on PGRA were
      dependent, in part, on an intact NID, the MAD, and N-terminal domain. In striking
      contrast, a FOXOA3 DNA-binding mutant (FOXOA3-mDBD) modulated PGRA, PGRB, and
      ESR1 activities by distinctly different mechanisms, markedly elevating ligand
      independent activity of these nuclear hormone receptors even in the double mutant
      lacking the MAD. Furthermore, both FOXOA3 and FOXOA3-mDBD enhanced the activity
      of a transcriptionally defective PGRA lacking its AF1 transactivation domain,
      indicating that this region of the receptor is not essential in this context.
      Since FOXOA3, FOXOA3-mDBD, and FOXOA3-mNID all bound PGRA in a GST pull-down
      assay, it appears that the LXXLL (leucine-X-X-leucine-leucine) motif within the
      NID is not critical for FOXOA3 interactions with PGRA, but may modify the
      recruitment of other co-regulatory molecules. Collectively, the results show that
      FOXOA3 exerts co-regulatory functions independent of DNA binding and that the DNA
      binding defective form of FOXO1a is transcriptionally active as a co-regulator of
      these nuclear hormone receptors.

PMID- 17556537
TI  - Communicable Disease and Health Protection Quarterly Review: October to December
      2006. From the Health Protection Agency, Centre for Infections.

PMID- 17556538
TI  - Can preoperative MRI accurately evaluate nodal and parametrial invasion in early
      stage cervical cancer?
AB  - OBJECTIVE: To evaluate the diagnostic performance of magnetic resonance imaging
      (MRI) in the pretreatment evaluation of invasive cervical cancer especially for
      the parametrial invasion and lymph node (LN) involvement. METHODS: We
      retrospectively recruited consecutive patients with biopsy-confirmed cervical
      cancer who had undergone preoperative MRI and were scheduled for surgery based on
      clinical assessment between January 2004 and May 2006. We evaluated the
      diagnostic performance of MRI for the parametrial invasion and LN involvement
      using surgicopathologic findings as the reference standard. RESULTS: A total of
      119 eligible patients completed preoperative and intra-operative survey, of whom
      34 (28.6%) had pelvic LN metastasis and four (3.4%) had para-aortic LN metastasis
      histologically. The sensitivity, specificity and accuracy of MRI in detecting LN
      involvement by region-specific analysis were 40.5, 91.3 and 86.8% respectively.
      The sensitivity, specificity and accuracy of MRI in detecting parametrial
      invasion were 44.4, 89.1 and 88.3% respectively. The positive predictive value
      (PPV) of preoperative MRI for detecting region-specific LN involvement and
      parametrial invasion was 31.3 and 61.2%, respectively. Imaging findings of
      suspected parametrial invasion were not to influence the treatment decision in
      the study. CONCLUSION: Preoperative MRI showed low PPV for detecting LN
      involvement and parametrial invasion in cervical cancer. Further studies are
      necessary to determine the cost-effectiveness of using MRI in place of
      conventional clinical staging tests according to clinical indication and also its
      use in comparison with that of integrated positron emission tomography/computed
      tomography.

PMID- 17556539
TI  - Dynamics of equilibrium structural fluctuations of apomyoglobin measured by
      fluorescence correlation spectroscopy.
AB  - The spectra of equilibrium chain conformation fluctuations of apomyoglobin
      (apoMb) as a function of folding, from the acid-denatured state at pH 2.6 through
      the stable molten globule state pH approximately 4.1 to the folded state at pH
      6.3, are reported, as measured by fluorescence correlation spectroscopy. The
      conformational fluctuations, which are detected by quenching of an N-terminal
      fluorescent label by contact with various amino acids, can be represented by
      superpositions of decaying exponentials with time scales ranging from
      approximately 3 to approximately 200 micros. Both the time scales and amplitudes
      of the fluctuations increase with the degree of acid denaturation, with principal
      shifts associated with the transition across the molten globule state.
      Measurements of the diffusion of apoMb confirm theoretical values showing a
      approximately 40% increase in the hydrodynamic radius upon acid denaturation.
      This study uses the model protein apoMb to illustrate the complex scope of
      folding associated structural dynamics.

PMID- 17556540
TI  - Radiocarbon and DNA evidence for a pre-Columbian introduction of Polynesian
      chickens to Chile.
AB  - Two issues long debated among Pacific and American prehistorians are (i) whether
      there was a pre-Columbian introduction of chicken (Gallus gallus) to the Americas
      and (ii) whether Polynesian contact with South America might be identified
      archaeologically, through the recovery of remains of unquestionable Polynesian
      origin. We present a radiocarbon date and an ancient DNA sequence from a single
      chicken bone recovered from the archaeological site of El Arenal-1, on the Arauco
      Peninsula, Chile. These results not only provide firm evidence for the pre
      Columbian introduction of chickens to the Americas, but strongly suggest that it
      was a Polynesian introduction.

PMID- 17556541
TI  - Presenilin/gamma-secretase-dependent processing of beta-amyloid precursor protein
      regulates EGF receptor expression.
AB  - Presenilins (PS, PS1/PS2) are necessary for the proteolytic activity of gamma
      secretase, which cleaves multiple type I transmembrane proteins including
      Alzheimer's beta-amyloid precursor protein (APP), Notch, ErbB4, etc. Cleavage by
      PS/gamma-secretase releases the intracellular domain (ICD) of its substrates.
      Notch ICD translocates into the nucleus to regulate expression of genes important
      for development. However, the patho/physiological role of other ICDs, especially
      APP ICD (AICD), in regulating gene expression remains controversial because
      evidence supporting this functionality stems mainly from studies performed under
      supraphysiological conditions. EGF receptor (EGFR) is up-regulated in a wide
      variety of tumors and hence is a target for cancer therapeutics. Abnormal
      expression/activation of EGFR contributes to keratinocytic carcinomas, and mice
      with reduced PS dosages have been shown to develop skin tumors. Here we
      demonstrate that the levels of PS and EGFR in the skin tumors of PS1(+/-)/ PS2(-/
      ) mice and the brains of PS1/2 conditional double knockout mice are inversely
      correlated. Deficiency in PS/gamma-secretase activity or APP expression results
      in a significant increase of EGFR in fibroblasts. Importantly, we show that AICD
      mediates transcriptional regulation of EGFR. Furthermore, we provide in vivo
      evidence demonstrating direct binding of endogenous AICD to the EGFR promoter.
      Our results indicate an important role of PS/gamma-secretase-generated APP
      metabolite AICD in gene transcription and in EGFR-mediated tumorigenesis.

PMID- 17556542
TI  - Regulatory small RNAs circumvent the conventional quorum sensing pathway in
      pandemic Vibrio cholerae.
AB  - Using a process called quorum sensing (QS), bacteria communicate with
      extracellular signal molecules called autoinducers (AIs). Response to AIs allows
      bacteria to coordinate gene expression on a population-wide scale and thereby
      carry out particular behaviors in unison, much like multicellular organisms. In
      Vibrio cholerae El Tor, the etiological agent of the current cholera pandemic, AI
      information is transduced internally through a phosphorelay circuit that impinges
      on the transcription of multiple small regulatory RNAs (sRNAs). These RNAs base
      pair with, and repress the translation of, the mRNA encoding the master
      transcriptional regulator HapR. In V. cholerae, HapR controls virulence factor
      expression and biofilm formation. Here we identify a sRNA-dependent, HapR
      independent QS pathway in which the sRNAs base-pair with a new target mRNA and
      activate translation by preventing formation of a translation-inhibiting stem
      loop structure. We show that the classical V. cholerae strain, which caused
      previous pandemics and is reportedly incapable of QS because of a nonfunctional
      HapR, nonetheless exhibits QS-controlled gene expression through this new HapR
      independent pathway.

PMID- 17556543
TI  - Ionic effects on viral DNA packaging and portal motor function in bacteriophage
      phi 29.
AB  - In many viruses, DNA is confined at such high density that its bending rigidity
      and electrostatic self-repulsion present a strong energy barrier in viral
      assembly. Therefore, a powerful molecular motor is needed to package the DNA into
      the viral capsid. Here, we investigate the role of electrostatic repulsion on
      single DNA packaging dynamics in bacteriophage phi 29 via optical tweezers
      measurements. We show that ionic screening strongly affects the packing forces,
      confirming the importance of electrostatic repulsion. Separately, we find that
      ions affect the motor function. We separate these effects through constant force
      measurements and velocity versus load measurements at both low and high capsid
      filling. Regarding motor function, we find that eliminating free Mg(2+) blocks
      initiation of packaging. In contrast, Na(+) is not required, but it increases the
      motor velocity by up to 50% at low load. Regarding internal resistance, we find
      that the internal force was lowest when Mg(2+) was the dominant ion or with the
      addition of 1 mM Co(3+). Forces resisting DNA confinement were up to
      approximately 80% higher with Na(+) as the dominant counterion, and only
      approximately 90% of the genome length could be packaged in this condition. The
      observed trend of the packing forces is in accord with that predicted by DNA
      charge-screening theory. However, the forces are up to six times higher than
      predicted by models that assume coaxial spooling of the DNA and interaction
      potentials derived from DNA condensation experiments. The forces are also
      severalfold higher than ejection forces measured with bacteriophage lambda.

PMID- 17556544
TI  - Activation of AMP-activated protein kinase by human EGF receptor 2/EGF receptor
      tyrosine kinase inhibitor protects cardiac cells.
AB  - The human EGF receptor (HER) 2 receptor tyrosine kinase is a survival factor for
      human cardiomyocytes, and its inhibition may explain the increased incidence of
      cardiomyopathy associated with the anti-HER2 monoclonal antibody trastuzumab
      (Genentech, South San Francisco, CA), particularly in patients with prior
      exposure to cardiotoxic chemotherapies e.g., anthracyclines. Here, we show that
      GW2974 (HER2/EGF receptor tyrosine kinase inhibitor), but not trastuzumab,
      activates AMP-activated protein kinase (AMPK), initiating a metabolic stress
      response in human cardiomyocytes that protects against TNFalpha-induced cell
      death. GW2974 stimulates calcium dependent fatty acid oxidation in vitro and in
      the myocardium of GW2974-treated rodents. Calcium chelation or siRNA-targeted
      AMPK knockdown blocks GW2974 induced fatty acid oxidation. In addition,
      inhibition of AMPK by a specific inhibitor resulted in increased killing of
      cardiomyocytes. Elucidating the effects of HER2-targeted therapies on AMPK may
      predict for risk of cardiomyopathy and provide a novel HER2-targeted strategy
      designed to protect myocardium from the pro-apoptotic effects of pro-inflammatory
      cytokines released in response to cardiac injury by chemotherapy or acute
      ischemia.

PMID- 17556545
TI  - Adipose tissue-specific inactivation of the retinoblastoma protein protects
      against diabesity because of increased energy expenditure.
AB  - The role of the tumor suppressor retinoblastoma protein (pRb) has been firmly
      established in the control of cell cycle, apoptosis, and differentiation.
      Recently, it was demonstrated that lack of pRb promotes a switch from white to
      brown adipocyte differentiation in vitro. We used the Cre-Lox system to
      specifically inactivate pRb in adult adipose tissue. Under a high-fat diet, pRb
      deficient (pRb(ad-/-)) mice failed to gain weight because of increased energy
      expenditure. This protection against weight gain was caused by the activation of
      mitochondrial activity in white and brown fat as evidenced by histologic,
      electron microscopic, and gene expression studies. Moreover, pRb(-/-) mouse
      embryonic fibroblasts displayed higher proliferation and apoptosis rates than
      pRb(+/+) mouse embryonic fibroblasts, which could contribute to the altered white
      adipose tissue morphology. Taken together, our data support a direct role of pRb
      in adipocyte cell fate determination in vivo and suggest that pRb could serve as
      a potential therapeutic target to trigger mitochondrial activation in white
      adipose tissue and brown adipose tissue, favoring an increase in energy
      expenditure and subsequent weight loss.

PMID- 17556546
TI  - Stimulation of subterritories of the subthalamic nucleus reveals its role in the
      integration of the emotional and motor aspects of behavior.
AB  - Two parkinsonian patients who experienced transient hypomanic states when the
      subthalamic nucleus (STN) was stimulated during postoperative adjustment of the
      electrical parameters for antiparkinsonian therapy agreed to have the mood
      disorder reproduced, in conjunction with motor, cognitive, and behavioral
      evaluations and concomitant functional neuroimaging. During the experiment, STN
      stimulation again induced a hypomanic state concomitant with activation of
      cortical and thalamic regions known to process limbic and associative
      information. This observation suggests that the STN plays a role in the control
      of a complex behavior that includes emotional as well as cognitive and motor
      components. The localization of the four contacts of the quadripolar electrode
      was determined precisely with an interactive brain atlas. The results showed that
      (i) the hypomanic state was caused only by stimulation through one contact
      localized in the anteromedial STN; (ii) both this contact and the contact
      immediately dorsal to it improved the parkinsonian motor state; (iii) the most
      dorsal and ventral contacts, located at the boundaries of the STN, neither
      induced the behavioral disorder nor improved motor performance. Detailed analysis
      of these data led us to consider a model in which the three functional
      modalities, emotional, cognitive, and motor, are not processed in a segregated
      manner but can be subtly combined in the small volume of the STN. This nucleus
      would thus serve as a nexus that integrates the motor, cognitive, and emotional
      components of behavior and might consequently be an effective target for the
      treatment of behavioral disorders that combine emotional, cognitive, and motor
      impairment.

PMID- 17556547
TI  - Social control of brain morphology in a eusocial mammal.
AB  - Social status impacts reproductive behavior in diverse vertebrate species, but
      little is known about how it affects brain morphology. We explore this in the
      naked mole-rat, a species with the most rigidly organized reproductive hierarchy
      among mammals. Naked mole-rats live in large, subterranean colonies where
      breeding is restricted to a single female and small number of males. All other
      members of the colony, known as subordinates, are reproductively suppressed.
      Subordinates can become breeders if removed from the colony and placed with an
      opposite sex partner, but in nature most individuals never attain reproductive
      status. We examined the brains of breeding and subordinate naked mole-rats of
      both sexes, including several regions linked to reproduction and shown to be
      sexually dimorphic in other mammals. Stereological analyses revealed that neural
      morphology depends on status, such that breeders, regardless of sex, had more
      cells than subordinates in the ventromedial nucleus of the hypothalamus and a
      larger volume of the bed nucleus of the stria terminalis, paraventricular
      nucleus, and medial amygdala. Several other brain regions examined were
      unaffected. Surprisingly, males and females did not differ on any measure. These
      findings provide evidence that a change in social status triggers considerable
      neural remodeling and indicate that status, rather than sex, has a predominant
      role in determining neural structure in this remarkably social mammal.

PMID- 17556549
TI  - Wireless power transfer via strongly coupled magnetic resonances.
AB  - Using self-resonant coils in a strongly coupled regime, we experimentally
      demonstrated efficient nonradiative power transfer over distances up to 8 times
      the radius of the coils. We were able to transfer 60 watts with approximately 40%
      efficiency over distances in excess of 2 meters. We present a quantitative model
      describing the power transfer, which matches the experimental results to within
      5%. We discuss the practical applicability of this system and suggest directions
      for further study.

PMID- 17556548
TI  - Parallels between cytokinesis and retroviral budding: a role for the ESCRT
      machinery.
AB  - During cytokinesis, as dividing animal cells pull apart into two daughter cells,
      the final stage, termed abscission, requires breakage of the midbody, a thin
      membranous stalk connecting the daughter cells. This membrane fission event
      topologically resembles the budding of viruses, such as HIV-1, from infected
      cells. We found that two proteins involved in HIV-1 budding-tumor susceptibility
      gene 101 (Tsg101), a subunit of the endosomal sorting complex required for
      transport I (ESCRT-I), and Alix, an ESCRT-associated protein-were recruited to
      the midbody during cytokinesis by interaction with centrosome protein 55 (Cep55),
      a centrosome and midbody protein essential for abscission. Tsg101, Alix, and
      possibly other components of ESCRT-I were required for the completion of
      cytokinesis. Thus, HIV-1 budding and cytokinesis use a similar subset of cellular
      components to carry out topologically similar membrane fission events.

PMID- 17556550
TI  - Rapid formation of supermassive black hole binaries in galaxy mergers with gas.
AB  - Supermassive black holes (SMBHs) are a ubiquitous component of the nuclei of
      galaxies. It is normally assumed that after the merger of two massive galaxies, a
      SMBH binary will form, shrink because of stellar or gas dynamical processes, and
      ultimately coalesce by emitting a burst of gravitational waves. However, so far
      it has not been possible to show how two SMBHs bind during a galaxy merger with
      gas because of the difficulty of modeling a wide range of spatial scales. Here we
      report hydrodynamical simulations that track the formation of a SMBH binary down
      to scales of a few light years after the collision between two spiral galaxies. A
      massive, turbulent, nuclear gaseous disk arises as a result of the galaxy merger.
      The black holes form an eccentric binary in the disk in less than 1 million years
      as a result of the gravitational drag from the gas rather than from the stars.

PMID- 17556551
TI  - Dentate gyrus NMDA receptors mediate rapid pattern separation in the hippocampal
      network.
AB  - Forming distinct representations of multiple contexts, places, and episodes is a
      crucial function of the hippocampus. The dentate gyrus subregion has been
      suggested to fulfill this role. We have tested this hypothesis by generating and
      analyzing a mouse strain that lacks the gene encoding the essential subunit of
      the N-methyl-d-aspartate (NMDA) receptor NR1, specifically in dentate gyrus
      granule cells. The mutant mice performed normally in contextual fear
      conditioning, but were impaired in the ability to distinguish two similar
      contexts. A significant reduction in the context-specific modulation of firing
      rate was observed in the CA3 pyramidal cells when the mutant mice were
      transferred from one context to another. These results provide evidence that NMDA
      receptors in the granule cells of the dentate gyrus play a crucial role in the
      process of pattern separation.

PMID- 17556552
TI  - New cooperation in East Asia.

PMID- 17556553
TI  - Stem cells. Teams reprogram differentiated cells--without eggs.

PMID- 17556554
TI  - Stem cells. Reprogramming, take two.

PMID- 17556556
TI  - CosmologY. Gravity distorts big bang afterglow, opening new window on cosmos.

PMID- 17556555
TI  - Academic tenure. MIT colleague quits to protest Sherley dismissal.

PMID- 17556557
TI  - Mongkol na Songkhla interview. Thai health minister defends controversial drug
      patent policy. Interview by Richard Stone.

PMID- 17556558
TI  - Saudi Arabia. Graduate university launched with $10 billion endowment.

PMID- 17556559
TI  - Conservation biology. Whales (mostly) win at Whaling Commission meeting.

PMID- 17556560
TI  - Climate change. Pushing the scary side of global warming.

PMID- 17556561
TI  - Alzheimer's disease. A new take on tau.

PMID- 17556563
TI  - 210th meeting of the American Astronomical Society. Black holes: galactic
      homebodies?

PMID- 17556562
TI  - Smallpox vaccine. A tame virus runs amok.

PMID- 17556564
TI  - 210th meeting of the American Astronomical Society. Exoplanet jackpot shows
      astronomers are looking for worlds in all the right places.

PMID- 17556565
TI  - 210th meeting of the American Astronomical Society. 'Pristine' galaxy gives a
      glimpse of purity.

PMID- 17556566
TI  - Adult versus embryonic stem cells: treatments.

PMID- 17556567
TI  - Making Singapore a research hub.

PMID- 17556568
TI  - Making data on Iraqi mortality rates available.

PMID- 17556570
TI  - Comment on "From plant traits to plant communities: a statistical mechanistic
      approach to biodiversity".
AB  - Shipley et al. (Reports, 3 November 2006, p. 812) predicted plant community
      composition and relative abundances with a high level of accuracy by maximizing
      Shannon's index of information entropy (species diversity), subject to
      constraints on plant trait averages. We show that the entropy maximization
      assumption is relatively unimportant and that the high accuracy is due largely to
      a statistical effect.

PMID- 17556569
TI  - Comment on "From plant traits to plant communities: a statistical mechanistic
      approach to biodiversity".
AB  - Shipley et al. (Reports, 3 November 2006, p. 812) developed a quantitative method
      for predicting the relative abundance of species from measured traits. We show
      that the method can have high explanatory power even when all trait and abundance
      data are randomly and independently generated, because of a mathematical
      dependence between the observations and predictions. We also suggest a potential
      solution to this problem.

PMID- 17556571
TI  - Science and security. Practical experiences in dual-use review.

PMID- 17556572
TI  - Physics. Cracking the supersolid.

PMID- 17556573
TI  - Physiology. Sister act.

PMID- 17556574
TI  - Biophysics. Long live electronic coherence!

PMID- 17556575
TI  - Geophysics. Listening to the crackle of subducting oceanic plates.

PMID- 17556576
TI  - Molecular biology. Site-seeing by sequencing.

PMID- 17556577
TI  - Imaging atomic structure and dynamics with ultrafast x-ray scattering.
AB  - Measuring atomic-resolution images of materials with x-ray photons during
      chemical reactions or physical transformations resides at the technological
      forefront of x-ray science. New x-ray-based experimental capabilities have been
      closely linked with advances in x-ray sources, a trend that will continue with
      the impending arrival of x-ray-free electron lasers driven by electron
      accelerators. We discuss recent advances in ultrafast x-ray science and coherent
      imaging made possible by linear-accelerator-based light sources. These studies
      highlight the promise of ultrafast x-ray lasers, as well as the technical
      challenges and potential range of applications that will accompany these
      transformative x-ray light sources.

PMID- 17556578
TI  - Expansion of industrial logging in Central Africa.
AB  - Industrial logging has become the most extensive land use in Central Africa, with
      more than 600,000 square kilometers (30%) of forest currently under concession.
      With use of a time series of satellite imagery for the period from 1976 to 2003,
      we measured 51,916 kilometers of new logging roads. The density of roads across
      the forested region was 0.03 kilometer per square kilometer, but areas of Gabon
      and Equatorial Guinea had values over 0.09 kilometer per square kilometer. A new
      frontier of logging expansion was identified within the Democratic Republic of
      Congo, which contains 63% of the remaining forest of the region. Tree felling and
      skid trails increased disturbance in selectively logged areas.

PMID- 17556579
TI  - Monochromatic electron photoemission from diamondoid monolayers.
AB  - We found monochromatic electron photoemission from large-area self-assembled
      monolayers of a functionalized diamondoid, [121]tetramantane-6-thiol.
      Photoelectron spectra of the diamondoid monolayers exhibited a peak at the low
      kinetic energy threshold; up to 68% of all emitted electrons were emitted within
      this single energy peak. The intensity of the emission peak is indicative of
      diamondoids being negative electron affinity materials. With an energy
      distribution width of less than 0.5 electron volts, this source of monochromatic
      electrons may find application in technologies such as electron microscopy,
      electron beam lithography, and field-emission flat-panel displays.

PMID- 17556580
TI  - Coherence dynamics in photosynthesis: protein protection of excitonic coherence.
AB  - The role of quantum coherence in promoting the efficiency of the initial stages
      of photosynthesis is an open and intriguing question. We performed a two-color
      photon echo experiment on a bacterial reaction center that enabled direct
      visualization of the coherence dynamics in the reaction center. The data revealed
      long-lasting coherence between two electronic states that are formed by mixing of
      the bacteriopheophytin and accessory bacteriochlorophyll excited states. This
      coherence can only be explained by strong correlation between the protein-induced
      fluctuations in the transition energy of neighboring chromophores. Our results
      suggest that correlated protein environments preserve electronic coherence in
      photosynthetic complexes and allow the excitation to move coherently in space,
      enabling highly efficient energy harvesting and trapping in photosynthesis.

PMID- 17556581
TI  - Stepwise quenching of exciton fluorescence in carbon nanotubes by single-molecule
      reactions.
AB  - Single-molecule chemical reactions with individual single-walled carbon nanotubes
      were observed through near-infrared photoluminescence microscopy. The emission
      intensity within distinct submicrometer segments of single nanotubes changed in
      discrete steps after exposure to acid, base, or diazonium reactants. The steps
      were uncorrelated in space and time and reflected the quenching of mobile
      excitons at localized sites of reversible or irreversible chemical attack.
      Analysis of step amplitudes revealed an exciton diffusional range of about 90
      nanometers, independent of nanotube structure. Each exciton visited about 10,000
      atomic sites during its lifetime, providing highly efficient sensing of local
      chemical and physical perturbations.

PMID- 17556582
TI  - Seismic evidence for deep-water transportation in the mantle.
AB  - We report seismic evidence for the transportation of water into the deep mantle
      in the subduction zone beneath northeastern Japan. Our data indicate that water
      is released from the hydrated oceanic crust at shallow depths (< approximately
      100 kilometers) and then forms a channel of hydrated mantle material on top of
      the subducting plate that is the pathway for water into the deep mantle. Our
      result provides direct evidence that shows how water is transported from the
      ocean to the deep mantle in a cold subduction zone environment.

PMID- 17556583
TI  - Global prevalence of double Benioff zones.
AB  - Double Benioff zones provide opportunities for insight into seismogenesis because
      the underlying mechanism must explain two layers of deep earthquakes and the
      separation between them. We characterize layer separation inside subducting
      plates with a coordinate rotation to calculate the slab-normal distribution of
      earthquakes. Benchmark tests on well-established examples confirm that layer
      separation is accurately quantified with global seismicity catalogs alone. Global
      analysis reveals double Benioff zones in 30 segments, including all 16 subduction
      zones investigated, with varying subducting plate ages and stress orientations,
      which implies that they are inherent in subducting plates. Layer separation
      increases with age and is more consistent with dehydration of antigorite than
      chlorite.

PMID- 17556584
TI  - A meta-analysis of effects of Bt cotton and maize on nontarget invertebrates.
AB  - Although scores of experiments have examined the ecological consequences of
      transgenic Bacillus thuringiensis (Bt) crops, debates continue regarding the
      nontarget impacts of this technology. Quantitative reviews of existing studies
      are crucial for better gauging risks and improving future risk assessments. To
      encourage evidence-based risk analyses, we constructed a searchable database for
      nontarget effects of Bt crops. A meta-analysis of 42 field experiments indicates
      that nontarget invertebrates are generally more abundant in Bt cotton and Bt
      maize fields than in nontransgenic fields managed with insecticides. However, in
      comparison with insecticide-free control fields, certain nontarget taxa are less
      abundant in Bt fields.

PMID- 17556585
TI  - An ancient mechanism controls the development of cells with a rooting function in
      land plants.
AB  - Root hairs and rhizoids are cells with rooting functions in land plants. We
      describe two basic helix-loop-helix transcription factors that control root hair
      development in the sporophyte (2n) of the angiosperm Arabidopsis thaliana and
      rhizoid development in the gametophytes (n) of the bryophyte Physcomitrella
      patens. The phylogeny of land plants supports the hypothesis that early land
      plants were bryophyte-like and possessed a dominant gametophyte and later the
      sporophyte rose to dominance. If this hypothesis is correct, our data suggest
      that the increase in morphological complexity of the sporophyte body in the
      Paleozoic resulted at least in part from the recruitment of regulatory genes from
      gametophyte to sporophyte.

PMID- 17556586
TI  - Polony multiplex analysis of gene expression (PMAGE) in mouse hypertrophic
      cardiomyopathy.
AB  - We describe a sensitive mRNA profiling technology, PMAGE (for "polony multiplex
      analysis of gene expression"), which detects messenger RNAs (mRNAs) as rare as
      one transcript per three cells. PMAGE incorporates an improved ligation-based
      method to sequence 14-nucleotide tags derived from individual mRNA molecules. One
      sequence tag from each mRNA molecule is amplified onto a separate 1-micrometer
      bead, denoted as a polymerase colony or polony, and about 5 million polonies are
      arrayed in a flow cell for parallel sequencing. Using PMAGE, we identified early
      transcriptional changes that preceded pathological manifestations of hypertrophic
      cardiomyopathy in mice carrying a disease-causing mutation. PMAGE provided a
      comprehensive profile of cardiac mRNAs, including low-abundance mRNAs encoding
      signaling molecules and transcription factors that are likely to participate in
      disease pathogenesis.

PMID- 17556587
TI  - Attenuation of allergic contact dermatitis through the endocannabinoid system.
AB  - Allergic contact dermatitis affects about 5% of men and 11% of women in
      industrialized countries and is one of the leading causes for occupational
      diseases. In an animal model for cutaneous contact hypersensitivity, we show that
      mice lacking both known cannabinoid receptors display exacerbated allergic
      inflammation. In contrast, fatty acid amide hydrolase-deficient mice, which have
      increased levels of the endocannabinoid anandamide, displayed reduced allergic
      responses in the skin. Cannabinoid receptor antagonists exacerbated allergic
      inflammation, whereas receptor agonists attenuated inflammation. These results
      demonstrate a protective role of the endocannabinoid system in contact allergy in
      the skin and suggest a target for therapeutic intervention.

PMID- 17556588
TI  - Hepatocyte nuclear factor-4 mediates apolipoprotein A-IV transcriptional
      regulation by fatty acid in newborn swine enterocytes.
AB  - Hepatocyte nuclear factor-4alpha (HNF-4alpha) regulates transcription of several
      genes involved in lipid metabolism, including that of apolipoprotein (apo) A-IV,
      which is tightly regulated by lipid absorption and enhances enterocyte
      chylomicron secretion. Studies were performed to define the role of HNF-4alpha in
      the regulation of apo A-IV gene transcription by dietary fatty acid in neonatal
      swine small intestine. HNF-4alpha mRNA was expressed in liver > intestine >
      kidney in suckling, weanling, and weaned pigs. Jejunal HNF-4alpha mRNA and
      protein and apo A-IV and swine microsomal triglyceride transfer protein (MTP)
      large subunit mRNA expression were induced in parallel in 2-day-old swine by a 24
      h high-fat intraduodenal infusion. In IPEC-1 cells, incubation with oleic acid
      (OA) resulted in coordinate induction of both HNF-4alpha, apo A-IV, and MTP mRNA,
      similar to that observed in vivo. When HNF-4alpha expression was driven by
      doxycycline by using the TET-On system in the absence of OA to observe the effect
      of HNF-4alpha directly on apo A-IV and MTP mRNA levels in the absence of other
      factors that might be concomitantly induced by fatty acid absorption, apo A-IV
      and MTP expression were increased. In luciferase reporter gene assays in IPEC-1
      cells using apo A-IV/C-III intergenic region constructs, TET-On-regulated HNF
      4alpha expression without OA increased luciferase activity, and incubation with
      OA did not further increase activity. These data suggest that acute induction of
      the apo A-IV and MTP genes by dietary lipid in newborn intestine occurs, at least
      in part, via ligand-independent transactivation by HNF-4alpha that is itself
      induced by a lipid-mediated mechanism.

PMID- 17556589
TI  - Distension during gastroesophageal reflux: effects of acid inhibition and
      correlation with symptoms.
AB  - We studied spontaneous gastroesophageal reflux (GER)-induced esophageal
      distension using ultrasound imaging and its role in the genesis of esophageal
      symptoms before and during esomeprazole therapy. Ten controls and 10 GER disease
      (GERD) patients were studied by combined impedance, esophageal pH, manometry, and
      ultrasonography before and during esomeprazole therapy. Physiological data and
      symptoms were recorded for 2 h following a standardized meal. From ultrasound
      images, the esophageal cross-sectional area (CSA) at the peak of GER-induced
      distension was determined and compared between controls vs. patients, symptomatic
      vs. asymptomatic GER episodes, and before vs. during esomeprazole in GERD
      patients. The mean lumen CSA is greater in the patients than controls (271 +/- 71
      mm(2) vs. 163 +/- 56 mm(2), P = 0.001) but not different among asymptomatic
      reflux episodes, and those associated with regurgitation (290 +/- 110 mm(2)) or
      heartburn (271 +/- 67 mm(2)). Eight chest pain episodes associated with reflux
      revealed a tendency toward larger mean esophageal distension (459 +/- 40 mm(2))
      compared with asymptomatic reflux (268 +/- 70 mm(2), P = 0.058). Following
      esomeprazole treatment, most GER episodes were nonacidic and asymptomatic except
      in two patients in whom cyclical reflux was associated with large esophageal
      distensions. Esomeprazole did not alter the lumen CSA during GER. Esophageal
      distension is greater in the GERD subjects compared with controls; however, it is
      unlikely that the GER-induced distension of the esophagus plays a significant
      role in the genesis of heartburn sensation. Esomeprazole therapy does not alter
      the GER-induced distension of the esophagus.

PMID- 17556590
TI  - CD19 expression in B cells is important for suppression of contact
      hypersensitivity.
AB  - Contact hypersensitivity (CHS) is a cutaneous immune reaction mediated mainly by
      antigen-specific effector T cells and is regarded as a model for Th1/Tc1-mediated
      inflammation. However, recent reports have suggested pivotal roles of B cells in
      CHS. CD19 serves as a positive B-cell response regulator that defines signaling
      thresholds critical for B-cell responses. In the current study, we assessed the
      role of the B-cell-specific surface molecule CD19 on the development of CHS by
      examining CD19-deficient mice. Although CD19-deficient mice are hyposensitive to
      a variety of transmembrane signals, CD19 loss resulted in increased and prolonged
      reaction of CHS, suggesting an inhibitory role of CD19 expression in CHS.
      Sensitized lymph nodes and elicited ear lesions from CD19-deficient mice
      exhibited Th1/Tc1-shifted cytokine profile with increased interferon-gamma
      expression and decreased interleukin-10 expression. Adoptive transfer experiments
      revealed that CD19 expression in recipient mice was required for optimal
      suppression of CHS response, indicating its role in the elicitation phase.
      Furthermore, spleen B cells, especially marginal zone B cells, from wild-type
      mice were able to normalize exaggerated CHS reactions in CD19-deficient mice.
      Thus, CD19 expression in B cells is critical for termination of CHS responses,
      possibly through the function of regulatory B cells.

PMID- 17556592
TI  - Foreign body giant cell formation is preceded by lamellipodia formation and can
      be attenuated by inhibition of Rac1 activation.
AB  - Macrophages that are recruited to the site of implanted biomaterials undergo
      fusion to form surface-damaging foreign body giant cells. Exposure of peripheral
      blood monocytes to interleukin-4 can recapitulate the fusion process in vitro. In
      this study, we used interleukin-4 to induce multinucleation of murine bone marrow
      derived macrophages and observed changes in cell shape, including elongation and
      lamellipodia formation, before fusion. Because cytoskeletal rearrangements are
      regulated by small GTPases, we examined the effects of inhibitors of Rho kinase
      (Y-32885) and Rac activation (NSC23766) on fusion. Y-32885 did not prevent
      cytoskeletal changes or fusion but limited the extent of multinucleation.
      NSC23766, on the other hand, inhibited lamellipodia formation and fusion in a
      dose-dependent manner. In addition, we found that in control cells, these changes
      were preceded by Rac1 activation. However, NSC23766 did not block the uptake of
      polystyrene microspheres. Likewise, short interfering RNA knockdown of Rac1
      limited fusion without limiting phagocytosis. Thus, phagocytosis and fusion can
      be partially decoupled based on their susceptibility to NSC23766. Furthermore,
      poly(ethylene-co-vinyl acetate) scaffolds containing NSC23766 attenuated foreign
      body giant cell formation in vivo. These observations suggest that targeting Rac1
      activation could protect biomaterials without compromising the ability of
      macrophages to perform beneficial phagocytic functions at implantation sites.

PMID- 17556591
TI  - Pericyte Rho GTPase mediates both pericyte contractile phenotype and capillary
      endothelial growth state.
AB  - Pericytes regulate microvascular development and maturation through the control
      of endothelial cell motility, proliferation, and differentiation. The Rho GTPases
      have recently been described as key regulators of pericyte shape and contractile
      phenotype by signaling through the actin cytoskeleton in an isoactin-specific
      manner. In this report, we reveal that Rho GTPase-dependent signal transduction
      not only influences pericyte shape and contractile potential but also modulates
      capillary endothelial proliferative status and pericyte-endothelial interactions
      in vitro. We provide evidence that overexpression of mutant Rho GTPases, but not
      other Ras-related small GTPases, significantly alters pericyte shape,
      contractility, and endothelial growth state in microvascular cell co-cultures. In
      particular, we describe the use of a silicon substrate deformation assay to
      demonstrate that pericyte contractility is Rho GTP- and Rho kinase-dependent;
      further, we describe a novel in vitro system for examining pericyte-mediated
      endothelial growth arrest and show that control pericytes are capable of growth
      arresting capillary endothelial cells in a cell contact-dependent manner, whereas
      pericytes overexpressing dominant-active and -negative Rho GTPase are comparably
      incompetent. These data strongly suggest that signaling through the pericyte Rho
      GTPase pathway may provide critical cues to the processes of microvascular
      stabilization, maturation, and contractility during development and disease.

PMID- 17556593
TI  - Tissue-specific effects of the nuclear factor kappaB subunit p50 on myocardial
      ischemia-reperfusion injury.
AB  - Nuclear factor kappaB (NF-kappaB) is a ubiquitous transcription factor activated
      by various stimuli implicated in ischemia-reperfusion injury. However, the role
      of NF-kappaB in cardiac ischemia-reperfusion injury has not yet been well
      defined. Therefore, we investigated reperfusion damage in mice with targeted
      deletion of the NF-kappaB subunit p50. Electrophoretic mobility shift assays
      validated NF-kappaB activation in wild-type (WT) but not p50 knockout (KO) mice.
      KO and WT animals underwent 30 minutes of coronary artery ligation and 24 hours
      of reperfusion in vivo. Ischemia-reperfusion damage was significantly reduced in
      the p50 KO when compared with matching WT mice. Although adhesion molecules such
      as intercellular adhesion molecule were up-regulated in left ventricles of p50 KO
      animals, fewer neutrophils infiltrated the infarct area, suggesting leukocytes as
      a potential mediator of the protection observed in the p50 KO. This was confirmed
      in adoptive transfer experiments: whereas transplantation of KO bone marrow in KO
      animals sustained the protective effect on ischemia-reperfusion injury,
      transplantation of WT bone marrow in KO animals abolished it. Thus, deletion of
      the NF-kappaB subunit p50 reduces ischemia-reperfusion injury in vivo, associated
      with less neutrophil infiltration. Bone marrow transplantation experiments
      indicate that impaired NF-kappaB activation in p50 KO leukocytes attenuates
      cardiac damage.

PMID- 17556596
TI  - A novel, immortal, and multipotent human neural stem cell line generating
      functional neurons and oligodendrocytes.
AB  - The discovery and study of neural stem cells have revolutionized our
      understanding of the neurogenetic process, and their inherent ability to adopt
      expansive growth behavior in vitro is of paramount importance for the development
      of novel therapeutics based on neural cell replacement. Recent advances in high
      throughput assays for drug development and gene discovery dictate the need for
      rapid, reproducible, long-term expansion of human neural stem cells (hNSCs). In
      this view, the complement of wild-type cell lines currently available is
      insufficient. Here we report the establishment of a stable human neural stem cell
      line (immortalized human NSCs [IhNSCs]) by v-myc-mediated immortalization of
      previously derived wild-type hNSCs. These cells demonstrate three- to fourfold
      faster proliferation than wild-type cells in response to growth factors but
      retain rather similar properties, including multipotentiality. By molecular
      biology, biochemistry, immunocytochemistry, fluorescence microscopy, and
      electrophysiology, we show that upon growth factor removal, IhNSCs completely
      downregulate v-myc expression, cease proliferation, and differentiate terminally
      into three major neural lineages: astrocytes, oligodendrocytes, and neurons. The
      latter are functional, mature cells displaying clear-cut morphological and
      physiological features of terminally differentiated neurons, encompassing mostly
      the GABAergic, glutamatergic, and cholinergic phenotypes. Finally, IhNSCs produce
      bona fide oligodendrocytes in fractions up to 20% of total cell number. This is
      in contrast to the negligible propensity of hNSCs to generate oligodendroglia
      reported so far. Thus, we describe an immortalized hNSC line endowed with the
      properties of normal hNSCs and suitable for developing the novel, reliable assays
      and reproducible high-throughput gene and drug screening that are essential in
      both diagnostics and cell therapy studies.

PMID- 17556595
TI  - Alteration of marrow cell gene expression, protein production, and engraftment
      into lung by lung-derived microvesicles: a novel mechanism for phenotype
      modulation.
AB  - Numerous animal studies have demonstrated that adult marrow-derived cells can
      contribute to the cellular component of the lung. Lung injury is a major variable
      in this process; however, the mechanism remains unknown. We hypothesize that
      injured lung is capable of inducing epigenetic modifications of marrow cells,
      influencing them to assume phenotypic characteristics of lung cells. We report
      that under certain conditions, radiation-injured lung induced expression of
      pulmonary epithelial cell-specific genes and prosurfactant B protein in
      cocultured whole bone marrow cells separated by a cell-impermeable membrane. Lung
      conditioned media had a similar effect on cocultured whole bone marrow cells and
      was found to contain pulmonary epithelial cell-specific RNA-filled microvesicles
      that entered whole bone marrow cells in culture. Also, whole bone marrow cells
      cocultured with lung had a greater propensity to produce type II pneumocytes
      after transplantation into irradiated mice. These findings demonstrate
      alterations of marrow cell phenotype by lung-derived microvesicles and suggest a
      novel mechanism for marrow cell-directed repair of injured tissue.

PMID- 17556594
TI  - Interferon-gamma induces chronic active myocarditis and cardiomyopathy in
      transgenic mice.
AB  - Chronic heart failure is associated with an activation of the immune system
      characterized among other factors by the cardiac synthesis and serum expression
      of proinflammatory cytokines. There is unequivocal clinical and experimental
      evidence that the cytokine tumor necrosis factor-alpha is involved in the
      development of chronic heart failure, but a putative cardiotoxic potential of the
      proinflammatory cytokine interferon (IFN)-gamma remains primarily unknown. To
      investigate this issue we analyzed the cardiac phenotype of SAP-IFN-gamma
      transgenic mice, which constitutively express IFN-gamma in their livers and hence
      exhibit high circulating serum levels of this cytokine. SAP-IFN-gamma mice
      spontaneously developed chronic active myocarditis, characterized by the
      infiltration of not only CD4(+) and CD8(+) T cells but also Mac2(+) (galectin
      3(+)) macrophages and CD11c(+) dendritic cells, eventually culminating in
      cardiomyopathy. Echocardiographic analyses exhibited a left ventricular dilation
      and impaired systolic function induced by IFN-gamma overexpression. IFN-gamma
      mediated cardiotoxicity was associated with high-level cardiac transcription of
      the proinflammatory cytokines tumor necrosis factor-alpha and interleukin-12 and
      the macrophage-attracting chemokines MCP1 and MIP1-alpha. Myotoxic IFN-gamma
      effects could not be detected in smooth or striated muscle tissue, suggesting
      cardiomyocellular specificity of the toxic IFN-gamma effect. The precise
      mechanism of IFN-gamma cardiotoxicity remains to be elucidated.

PMID- 17556597
TI  - Functional network analysis of the transcriptomes of mesenchymal stem cells
      derived from amniotic fluid, amniotic membrane, cord blood, and bone marrow.
AB  - Using high-density oligonucleotide microarrays and functional network analyses,
      we examined whether MSCs derived from four different origins exhibited unique
      gene expression profiles individually and then compared the gene expression
      profiles of all MSCs with those of fetal organs. Our results indicated that
      within each group of MSCs from the same origin, the variability of the gene
      expression levels was smaller than that between groups of different origins.
      Functional genomic studies revealed the specific roles of MSCs from different
      origins. Our results suggest that amniotic fluid MSCs may initiate interactions
      with the uterus by upregulating oxytocin and thrombin receptors. Amniotic
      membrane MSCs may play a role in maintaining homeostasis of fluid and
      electrolytes by regulating the networks of endothelin, neprilysin, bradykinin
      receptors, and atrial natriuretic peptide. Cord blood MSCs may be involved in
      innate immune systems as the neonatal defense system against the earliest
      encountered pathogens. Adult bone marrow MSCs may be an important source not only
      of all blood lineages but also of bone formation. However, in spite of the
      different gene expression profiles seen in MSCs derived from different origins, a
      set of core gene expression profiles was preserved in these four kinds of MSCs.
      The core signature transcriptomes of all MSCs, when contrasted against those of
      fetal organs, included genes involved in the regulation of extracellular matrix
      and adhesion, transforming growth factor-beta receptor signaling, and the Wnt
      signaling pathways. Disclosure of potential conflicts of interest is found at the
      end of this article.

PMID- 17556598
TI  - Differentiation of human embryonic stem cells in serum-free medium reveals
      distinct roles for bone morphogenetic protein 4, vascular endothelial growth
      factor, stem cell factor, and fibroblast growth factor 2 in hematopoiesis.
AB  - We have utilized a serum- and stromal cell-free "spin embryoid body (EB)"
      differentiation system to investigate the roles of four growth factors, bone
      morphogenetic protein 4 (BMP4), vascular endothelial growth factor (VEGF), stem
      cell factor (SCF), and basic fibroblast growth factor (FGF2), singly and in
      combination, on the generation of hematopoietic cells from human embryonic stem
      cells (HESCs). Of the four factors, only BMP4 induced expression of genes that
      signaled the emergence of the primitive streak-like population required for the
      subsequent development of hematopoietic mesoderm. In addition, BMP4 initiated the
      expression of genes marking hematopoietic mesoderm and supported the generation
      of hematopoietic progenitor cells at a low frequency. However, the appearance of
      robust numbers of hematopoietic colony forming cells and their mature progeny
      required the inclusion of VEGF. Finally, the combination of BMP4, VEGF, SCF, and
      FGF2 further enhanced the total yield of hematopoietic cells. These data
      demonstrate the utility of the serum-free spin EB system in dissecting the roles
      of specific growth factors required for the directed differentiation of HESCs
      toward the hematopoietic lineage.

PMID- 17556599
TI  - Oxygen tension regulates survival and fate of mouse central nervous system
      precursors at multiple levels.
AB  - Despite evidence that oxygen regulates neural precursor fate, the effects of
      changing oxygen tensions on distinct stages in precursor differentiation are
      poorly understood. We found that 5% oxygen permitted clonal and long-term
      expansion of mouse fetal cortical precursors. In contrast, 20% oxygen caused a
      rapid decrease in hypoxia-inducible factor 1alpha and nucleophosmin, followed by
      the induction of p53 and apoptosis of cells. This led to a decrease in overall
      cell number and particularly a loss of astrocytes and oligodendrocytes. Clonal
      analysis revealed that apoptosis in 20% oxygen was due to a complete loss of
      CD133(lo)CD24(lo) multipotent precursors, a substantial loss of CD133(hi)CD24(lo)
      multipotent precursors, and a failure of remaining CD133(hi)CD24(lo) cells to
      generate glia. In contrast, committed neuronal progenitors were not significantly
      affected. Switching clones from 5% to 20% oxygen only after mitogen withdrawal
      led to a decrease in total clone numbers but an even greater decrease in
      oligodendrocyte-containing clones. During this late exposure to 20% oxygen,
      bipotent glial (A2B5+) and early (platelet-derived growth factor receptor alpha)
      oligodendrocyte progenitors appeared and disappeared more quickly, relative to 5%
      oxygen, and late stage O4+ oligodendrocyte progenitors never appeared. These
      results indicate that multipotent cells and oligodendrocyte progenitors are more
      susceptible to apoptosis at 20% oxygen than committed neuronal progenitors. This
      has important implications for optimizing ex vivo production methods for cell
      replacement therapies.

PMID- 17556600
TI  - Acquired immunity in a holoendemic setting of Plasmodium falciparum and p. Vivax
      malaria.

PMID- 17556601
TI  - The risk of malarial infections and disease in Papua New Guinean children.
AB  - In a treatment re-infection study of 206 Papua New Guinean school children, we
      examined risk of reinfection and symptomatic malaria caused by different
      Plasmodium species. Although children acquired a similar number of polymerase
      chain reaction-detectable Plasmodium falciparum and P. vivax infections in six
      months of active follow-up (P. falciparum = 5.00, P. vivax = 5.28), they were 21
      times more likely to develop symptomatic P. falciparum malaria (1.17/year) than
      P. vivax malaria (0.06/year). Children greater than nine years of age had a
      reduced risk of acquiring P. vivax infections of low-to-moderate (>150/microL)
      density (adjusted hazard rate [AHR] = 0.65 and 0.42), whereas similar reductions
      in risk with age of P. falciparum infection was only seen for parasitemias >
      5,000/microL (AHR = 0.49) and symptomatic episodes (AHR = 0.51). Infection and
      symptomatic episodes with P. malariae and P. ovale were rare. By nine years of
      age, children have thus acquired almost complete clinical immunity to P. vivax
      characterized by a very tight control of parasite density, whereas the
      acquisition of immunity to symptomatic P. falciparum malaria remained incomplete.
      These observations suggest that different mechanisms of immunity may be important
      for protection from these malaria species.

PMID- 17556602
TI  - Spatial analysis of malaria transmission parameters in the rice cultivation area
      of Office du Niger, Mali.
AB  - The effects of rice growth environment on malaria transmission, taking into
      account spatial correlation, were assessed in the Office du Niger, Mali. Between
      April 1999 to January 2001, 8 quarterly entomologic surveys were conducted in 18
      villages in 3 agricultural zones. Vector densities in sleeping houses were
      related to rice crop, rice development stages, vegetation abundance, water state,
      and seasons. They were high throughout the rice-growing seasons, increased as the
      rice crop developed, and decreased as vegetation became abundant. They also
      showed large spatial correlations (up to 30.6 km). The vectorial capacity
      exhibited both seasonal and village-to-village variation. Parity and the human
      blood index were weakly related to adult densities and showed low spatial
      correlations (up to 3.4 km), which suggested that small area variation in malaria
      transmission results mainly from variations in vector-human contact. Control
      strategies in rice cultivation areas should pay attention to this local
      variation.

PMID- 17556603
TI  - CLINICAL case report: falciparum malaria with hemophagocytic syndrome.
AB  - A 30-year-old Japanese woman with falciparum malaria was hospitalized because of
      fever and renal failure, and prolonged anemia was identified despite the
      eradication of malaria parasites through anti-malaria therapy. Bone marrow
      aspiration revealed the presence of macrophages with hemophagocytosis, and serum
      interleukin (IL)-18 and tumor necrosis factor (TNF)-alpha levels were high in the
      anemic phase. Hemophagocytosis was confirmed for at least 3 weeks, and prolonged
      hemophagocytic syndrome is thought to be one of the causes of prolonged anemia in
      patients with falciparum malaria.

PMID- 17556604
TI  - A comparison of sulfadoxine-pyrimethamine with chloroquine and pyrimethamine for
      prevention of malaria in pregnant Nigerian women.
AB  - Few studies have documented the effectiveness in west Africa of intermittent
      preventive treatment of malaria with sulfadoxine-pyrimethamine (SP) in pregnancy.
      Pregnant Nigerian women were assigned to receive either SP given twice or
      presumptive chloroquine (CQ) treatment followed by weekly pyrimethamine (CQ + P);
      250 were enrolled in each group. Of those completing follow-up, 4 (1.8%) in the
      SP group and 22 (9.8%) in the CQ + P groups had a febrile illness (P = 0.005).
      None in the SP group but 11 (4.9%) in the CQ + P group had peripheral parasitemia
      prior to or during delivery (P = 0.002). Two (1.2%) in the SP group and 9 (5.0%)
      in the CQ + P group were anemic at delivery (P = 0.04). There were six low birth
      weight infants in the SP group and eight in the CQ + P group (P = 0.21).
      Intermittent preventive treatment with SP is superior to CQ + P for prevention of
      malaria and anemia in pregnant women in Nigeria.

PMID- 17556605
TI  - In vitro susceptibility of P. falciparum populations from Colombia and Tanzania
      to a new synthetic peroxide (OZ277).
AB  - Sensitivity of Plasmodium falciparum populations from Colombia (N = 38) and
      Tanzania (N = 45) to the newly developed, fully synthetic peroxide OZ277 was
      investigated using a standard isotopic microtest. OZ277 showed excellent activity
      against chloroquine-resistant isolates in Colombia with median IC(50) [range]
      values of 2.5 ng/mL [0.34-8] (4.4 nM [0.6-14]) and Tanzania with 1.5 ng/mL [0.22
      10] (2.65 nM [0.4-17.7]). The potency of OZ277 was similar to artesunate, showing
      median IC(50) values of 1.5 ng/mL [0.42-8.6] (3.8 nM [1.1-22.3]) and 1.8 ng/mL
      [0.2-10] (4.7 nM [0.5-26.04]) in Colombia and Tanzania, respectively. These
      results support the development of this new antimalarial compound.

PMID- 17556606
TI  - Factors influencing the effectiveness of malaria control in Bioko Island,
      equatorial Guinea.
AB  - The Bioko Island Malaria Control Project (BIMCP) has carried out intensive
      interventions since early 2004 to reduce malaria transmission through indoor
      residual spraying (IRS) and case management. Annual parasite prevalence surveys
      have been carried out to monitor the effectiveness of the program. Significant
      overall reductions in prevalence of infection have been observed, with 42% fewer
      infections occurring in 2006 compared with baseline. Nevertheless, there is
      evidence of considerable heterogeneity in impact of the intervention. Prevalence
      of infection was significantly associated with spray status of the child's house,
      spray coverage with effective insecticide of the neighborhood of the house, bed
      net use, and time elapsed since last spray. Careful scheduling of spray coverage
      is therefore essential to maximize the effectiveness of IRS and to ensure
      consistent reductions in parasite prevalence. This can only be achieved if
      comprehensive monitoring systems are in place for both the management and
      evaluation of the intervention.

PMID- 17556607
TI  - Higher production of peripheral blood macrophage migration inhibitory factor in
      healthy children with a history of mild malaria relative to children with a
      history of severe malaria.
AB  - Plasmodium falciparum malaria is one of the leading causes of childhood morbidity
      and mortality in sub-Saharan Africa. The host immune response to P. falciparum is
      a critical determinant of malarial pathogenesis and disease outcomes. Macrophage
      migration inhibitory factor (MIF) is a central regulator of innate immune
      responses to bacterial and parasitic infections. Our recent investigations
      demonstrated that peripheral blood MIF production was suppressed in children with
      severe malaria. Because examination of MIF production in children with active
      disease does not account for the inherent ability of the host to generate MIF,
      basal circulating MIF and peripheral blood mononuclear cell (PBMC) MIF transcript
      levels were determined in healthy children with a history of either mild or
      severe malaria. Children with prior mild malaria had higher plasma MIF levels and
      PBMC MIF transcripts than children with an identical number of previous episodes
      of severe malaria. These results suggest that increased basal MIF production may
      be important in generating immune responses that protect against the development
      of severe malaria.

PMID- 17556608
TI  - High frequency of recombination-driven allelic diversity and temporal variation
      of Plasmodium falciparum msp1 in Tanzania.
AB  - A major mechanism for the generation allelic diversity in the Plasmodium
      falciparum msp1 gene is meiotic recombination in the Anopheles mosquito. The
      frequency of recombination events is dependent on the intensity of transmission.
      Herein we investigate the frequency of recombination-driven allelic diversity and
      temporal variation of msp1 in Rufiji, eastern coastal Tanzania, where malaria
      transmission is intense. We identified 5' recombinant types, 3' sequence types,
      and msp1 haplotypes (unique associations of 5' recombinant types and 3' sequence
      types) to measure the extent and temporal variation of msp1 allelic diversity.
      The results show that msp1 haplotype diversity is higher in Tanzania as compared
      with areas with lower transmission rates. The frequencies of individual
      polymorphic regions/sites remained stable during the study period. However, the
      frequency distribution of msp1 haplotypes varied between 1993 and 1998. These
      results suggest that frequent recombination events between msp1 alleles
      intermittently generate novel alleles in high transmission areas.

PMID- 17556610
TI  - Enhanced malaria parasite transmission from helminth co-infected mice.
AB  - Helminth infections are prevalent in malaria-endemic areas, yet the potential for
      helminths to alter malaria transmission has not been closely examined. We used
      the Echinostoma caproni-Plasmodium yoelii murine model of co-infection to assess
      the impact of helminth co-infection on malaria transmission. In four replicate
      experiments, Anopheles stephensi mosquitoes exposed to co-infected mice five days
      post-malaria infection had a higher rate of infectivity (80.1%, n = 241) than
      those exposed to malaria only-infected mice (72.0%, n = 232, P = 0.039).
      Intensity of malaria parasite transmission was also greater, with approximately
      two-fold more oocysts (geometric mean = 19.2 versus 10.5, P = 0.004) and an
      increase in sporozoite burden observed in mosquitoes exposed to co-infected mice.
      Malaria parasite prevalence and anemia were similar between co-infected and
      malaria only-infected mice, which suggested that enhanced malaria parasite
      transmission was due to helminth-induced modulation of host responses.

PMID- 17556609
TI  - Restricted T-cell epitope diversity in the circumsporozoite protein from
      Plasmodium falciparum populations prevalent in Iran.
AB  - Parasite genotyping studies have indicated that the Plasmodium falciparum
      populations circulating in Iran are genetically diverse and that multiple
      genotype infections are observed regularly. We wished to extend the analysis to
      the Pfcsp gene, coding for the dominant sporozoite surface antigen on which the
      leading malaria vaccine candidate RTS,S is based. Infected blood samples were
      collected mainly from Iranian, as well as Afghani and Pakistani, patients on
      admission with falciparum malaria. DNA was purified from 90 isolates, and from
      these, 21 fragments corresponding to Pfcsp and 69 fragments corresponding to the
      3'-end conserved domain were amplified and sequenced. Overall diversity was low.
      Six patterns were noted for the repeat region, but mixed genotypes were not
      observed in any of the isolates. T cell epitopes also displayed limited
      diversity, with only five haplotypes (combined Th2R/Th3R epitopes) noted, and of
      these, three were dominant, accounting for 94% of the 90 sequences. These
      observations are akin to those observed in Thai P. falciparum isolates, where a
      particular Pfscp Th2R/Th3R haplotype seems to be maintained in an otherwise
      genetically diverse parasite population. The data imply that the selective
      pressure that maintains a restricted T cell epitope is caused by factors outside
      the mammalian host immune responses. Furthermore, they sustain the notion that
      protective responses induced by RTS,S vaccination are not strain-specific.

PMID- 17556611
TI  - Sensitivity to antifolates and genetic analysis of Plasmodium vivax isolates from
      Thailand.
AB  - We investigated the association between the Plasmodium vivax dihydrofolate
      reductase (Pvdhfrtas) and the P. vivax dihydropteroate synthase (Pvdhps) genotype
      and in vitro sensitivity to the antifolates pyrimethamine, WR99210,
      chlorcycloguanil, sulfadoxine, and dapsone. Drug responses of 32 P. vivax
      isolates were assessed in two in vitro systems: schizont maturation inhibition
      and a yeast expression system. The geometric mean of 50% inhibition concentration
      (IC(50)) values for pyrimethamine, chlorcycloguanil, WR99210, sulfadoxine, and
      dapsone were 85 +/- 88, 784 +/- 662, 95 +/- 87, 2,424 +/- 2,784, and 1,625 +/-
      1,801 nM, respectively, for the schizont maturation assay. Five different Pvdhfr
      alleles and four Pvdhps alleles were observed: 26 of 32 quadruple mutant alleles
      of Pvdhfr (F57I,L/S58R/T61M/S117T), four triple mutants (S58R/T61M/S117T,
      K49C/S58R/S117N), and two double mutant isolates (S58R/S117N). All isolates
      carried Pvdhps 585V. Twenty four isolates carried double mutant Pvdhps
      (A383G/A553G), six an additional mutation, S382A,C/A383G/A553G, and two a single
      mutation, A383G. Increasing geometric mean IC(50) values were observed with
      increased number of Pvdhfr mutations from double to quadruple. Results suggest
      that quadruple mutant alleles confer decreased sensitivity to pyrimethamine but
      retain sensitivity to WR99210.

PMID- 17556612
TI  - Effects of maternal vitamin supplements on malaria in children born to HIV
      infected women.
AB  - Vitamin deficiencies are frequent in children suffering from malaria. The effects
      of maternal multivitamin supplementation on the risk of malaria in children are
      unknown. We examined the impact of providing multivitamins or vitamin A/beta
      carotene supplements during pregnancy and lactation to HIV-infected women on
      their children's risk of malaria up to 2 years of age, in a randomized, placebo
      controlled trial. Tanzanian women (N = 829) received one of four daily oral
      regimens during pregnancy and after delivery: 1) vitamins B, C, and E
      (multivitamins); 2) vitamin A and beta-carotene (VA/BC); 3) multivitamins
      including VA/BC; or 4) placebo. After 6 months of age, all children received 6
      monthly oral vitamin A supplements irrespective of treatment arm. The incidence
      of childhood malaria was assessed through three-monthly blood smears and at
      monthly and interim clinic visits from birth to 24 months of age. Compared with
      placebo, multivitamins excluding VA/BC reduced the incidence of clinical malaria
      by 71% (95% CI = 11-91%; P = 0.02), whereas VA/BC alone resulted in a
      nonsignificant 63% reduction (95% CI = -4% to 87%; P = 0.06). Multivitamins
      including VA/BC significantly reduced the incidence of high parasitemia by 43%
      (95% CI = 2-67%; P = 0.04). The effects did not vary according to the children's
      HIV status. Supplementation of pregnant and lactating HIV-infected women with
      vitamins B, C, and E might be a useful, inexpensive intervention to decrease the
      burden of malaria in children born to HIV-infected women in sub-Saharan Africa.

PMID- 17556613
TI  - Genetic control of malaria parasite transmission: threshold levels for infection
      in an avian model system.
AB  - Genetic strategies for controlling malaria transmission based on engineering
      pathogen resistance in Anopheles mosquitoes are being tested in a number of
      animal models. A key component is the effector molecule and the efficiency with
      which it reduces parasite transmission. Single-chain antibodies (scFvs) that bind
      the circumsporozoite protein of the avian parasite, Plasmodium gallinaceum, can
      reduce mean intensities of sporozoite infection of salivary glands by two to four
      orders of magnitude in transgenic Aedes aegypti. Significantly, mosquitoes with
      as few as 20 sporozoites in their salivary glands are infectious for a vertebrate
      host, Gallus gallus. Although scFvs hold promise as effector molecules, they will
      have to reduce mean intensities of infection to zero to prevent parasite
      transmission and disease. We conclude that similar endpoints must be reached with
      human pathogens if we are to expect an effect on disease transmission.

PMID- 17556614
TI  - Prevalent pfmdr1 n86y mutant Plasmodium falciparum in Madagascar despite absence
      of pfcrt mutant strains.
AB  - We assessed the status of point mutations associated with chloroquine resistance
      in pfcrt codon 76 and in pfmdr1 codon 86 among Plasmodium falciparum isolates
      from symptomatic patients in 3 sites in Madagascar. The in vitro susceptibility
      of P. falciparum isolates to quinoline-containing drugs was also determined. All
      isolates (N = 117) successfully typed were pfcrt wild-type, except one from
      Tsiroanomandidy (1 of 27). However, 67.5% (95% CI: 58.2-75.9%) of these isolates
      contained mutant pfmdr1 86Y. The pfmdr1 N86Y mutation is associated with higher
      mefloquine susceptibility, but it did not affect the sensitivity of parasites to
      chloroquine or quinine. Our findings demonstrate that pfmdr1 mutant P. falciparum
      are prevalent in Madagascar and confirm the low prevalence of pfcrt mutant P.
      falciparum after 60 years of chloroquine use. They provide additional field-based
      evidence for increased mefloquine susceptibility in pfmdr1 mutant P. falciparum
      and are suggestive of the intrahost selection of pfmdr1 mutant parasites.

PMID- 17556615
TI  - Variant-specific antibodies to merozoite surface protein 2 and clinical
      expression of Plasmodium falciparum malaria in rural Amazonians.
AB  - Naturally acquired antibodies to five variants of the merozoite surface protein 2
      (MSP-2), a target of clinical immunity to Plasmodium falciparum malaria, were
      measured in a cohort of rural Amazonians. Local MSP-2 variants comprised both
      highly divergent families of alleles (FC27 and 3D7). Total IgG antibodies to two
      FC27-type antigens were found in 22-28% of subjects at baseline, with substantial
      cross-reactivity between variants and stable concentrations and specificities
      over time. The IgG antibodies to three 3D7-type antigens were less prevalent (6
      7%), less cross-reactive, and short-lived; subsequent exposure to 3D7-type
      parasites rarely elicited homologous response. The clinical spectrum of 109
      incident P. falciparum infections in our cohort ranged between asymptomatic
      infection and fully symptomatic but uncomplicated disease. Parasitemia at the
      time of diagnosis, rather than cumulative malaria exposure or acquired immunity
      (presence of variant-specific antibodies matching the MSP-2 type in infecting
      parasites), was a major predictor of perceived symptom severity.

PMID- 17556616
TI  - Comparison of HRP2- and pLDH-based rapid diagnostic tests for malaria with
      longitudinal follow-up in Kampala, Uganda.
AB  - Presumptive treatment of malaria results in significant overuse of antimalarials.
      Malaria rapid diagnostic tests (RDTs) may offer a reliable alternative for case
      management, but the optimal RDT strategy is uncertain. We compared the diagnostic
      accuracy of histidine-rich protein 2 (HRP2)- and plasmodium lactate dehydrogenase
      (pLDH)-based RDTs, using expert microscopy as the gold standard, in a
      longitudinal study of 918 fever episodes over an 8-month period in a cohort of
      children in Kampala, Uganda. Sensitivity was 92% for HRP2 and 85% for pLDH, with
      differences primarily due to better detection with HRP2 at low parasite
      densities. Specificity was 93% for HRP2 and 100% for pLDH, with differences
      primarily due to rapid clearance of pLDH antigenemia after treatment of a
      previous malaria episode. RDTs may provide an effective strategy for improving
      rational delivery of antimalarial therapy; in Kampala, either test could
      dramatically decrease inappropriate presumptive treatments.

PMID- 17556617
TI  - Positive blood culture with Plasmodium falciparum: case report.
AB  - An adult traveler presented with fever and malaise after returning from Sierra
      Leone. Young trophozoites of Plasmodium falciparum were seen in a blood smear,
      with parasitemia being 10%. Moreover, blood cultures drawn on admission signaled
      as "positive" after 1 day of incubation, but no bacteria were seen in the Gram
      stain or were subcultured. A Giemsa-stained smear from the positive bottle
      contents yielded numerous pigmented, mature trophozoites of P. falciparum. This
      case indicates that, in patients with malaria, the growth of P. falciparum in
      blood cultures can result in "false"-positive blood cultures.

PMID- 17556618
TI  - Distribution of free untreated bednets bundled with insecticide via an integrated
      child health campaign in Lindi Region, Tanzania: lessons for future campaigns.
AB  - Use of insecticide-treated bednets (ITNs) to prevent malaria remains low, and
      effective distribution strategies are needed. An integrated child health campaign
      with free distribution of 162,254 untreated bednets bundled with insecticide,
      measles vaccination, vitamin A, and mebendazole for children < 5 years old
      ("under-5s") was conducted in Lindi Region, Tanzania. We conducted a
      representative household survey 3 months after the campaign. Altogether, 574
      households with 354 under-5s were visited. In households with an under-5,
      possession of bednets and ITNs increased from 60.9% to 90.7% (P < 0.001) and from
      16.5% to 37.3% (P < 0.001), respectively. Increases occurred in all wealth
      quintiles and equity improved. Reported bednet and ITN use the previous night
      among under-5s was 46.3% and 21.5%, respectively. Integrated campaigns rapidly
      and equitably increase bednet possession and use meriting continued large-scale
      implementation. However, our study found that bednets were rarely treated; thus,
      future campaigns should provide factory-treated long-lasting ITNs. Low ITN use
      underscores the need for further efforts to increase use after campaigns.

PMID- 17556619
TI  - In vitro antimalarial susceptibility profile and prcrt/pfmdr-1 genotypes of
      Plasmodium falciparum field isolates from Malawi.
AB  - We measured in vitro antimalarial drug susceptibility of 84 Plasmodium falciparum
      field isolates from Blantyre, Southern Malawi, using the WHO microtest and the
      lactate dehydrogenase assay. We also genotyped these isolates to investigate
      whether variation in their absolute drug sensitivity is associated with specific
      sets of pfcrt and pfmdr-1 mutations harbored by parasites. Our results show that
      nearly a decade after the withdrawal of chloroquine (CQ) as a first-line
      antimalarial in Malawi, most isolates are now sensitive to CQ and none is CQ
      resistant as predicted by their drug sensitivity phenotype and pfcrt genotype. We
      also found that these isolates are uniformly sensitive to a range of quinoline
      based antimalarials and artemisinin derivatives. These findings reinforce
      previous reports about a reduction in the proportion of CQ-resistant parasites
      after the withdrawal of CQ in 1993 and pave the way for reassessing the clinical
      usefulness of CQ, artemisinins and other quinoline-based antimalarials in Malawi.

PMID- 17556620
TI  - A newly recognized species in the Anopheles (Nyssorhynchus) albitarsis complex
      (Diptera: Culicidae) from Puerto Carreno, Colombia.
AB  - We report a previously unrecognized mosquito species from eastern Colombia
      belonging to the Anopheles (Nyssorhynchus) albitarsis complex. We provisionally
      name this taxon An. albitarsis species "F." Until now, the only members of the
      Albitarsis Complex recorded from north of the Amazon River have been An.
      marajoara and a putative phylogenetic species, An. albitarsis "E." As with the
      other largely monomorphic species in the complex, we were able to detect its
      presence using ribosomal DNA internal transcribed spacer 2 (rDNA ITS2) and
      partial white gene sequences. Unlike An. marajoara, but in common with other
      species in the complex, An. albitarsis F lacks the white gene fourth intron. This
      species is sympatric with An. marajoara in a malaria-endemic area in Puerto
      Carreno, Vichada Department, Colombia. It could be an important current and/or
      historical vector of human malaria parasites at this locality and, depending on
      its actual distribution, elsewhere in Colombia and Venezuela.

PMID- 17556621
TI  - The Anopheles gambiae vitellogenin gene (VGT2) promoter directs persistent
      accumulation of a reporter gene product in transgenic Anopheles stephensi
      following multiple bloodmeals.
AB  - Mosquitoes made resistant to pathogens through genetic engineering are proposed
      as a basis for developing a strategy to control disease transmission. Transgenic
      approaches that introduce exogenous antipathogen effector genes into mosquito
      genomes require cis-acting regulatory DNA to control tissue-, stage-, and sex
      specific transgene expression. We show that control sequences derived from a
      vitellogenin-encoding gene of Anopheles gambiae, a major vector in sub-Saharan
      Africa, can direct expression of an exogenous gene in a tissue-, stage-, and sex
      specific manner in Anopheles stephensi, a vector of urban malaria in southern
      Asia. Specific reporter gene expression was observed in fat-body tissues of
      transgenic blood-fed females, but not in transgenic males or non-blood-fed
      transgenic females. Multiple bloodmeals resulted in the continuous presence of
      reporter gene transcripts for at least 12 days. The persistent expression makes
      the heterologous promoter a good candidate for controlling transcription of
      engineered antipathogen effector genes in this important malaria vector.

PMID- 17556623
TI  - Parenteral aminosidine is not effective for Peruvian mucocutaneous leishmaniasis.
AB  - Few therapeutic options are available for mucocutaneous leishmaniasis (MCL). We
      conducted a randomized open trial to evaluate the efficacy, safety, and tolerance
      of parenteral aminosidine sulphate (AS) 14 mg/kg/d for 21 days compared with
      intravenous meglumine antimonate (MA) 20 mg/kg/d for 28 days in patients with
      moderate MCL in Cuzco, Peru. Cure was defined as complete healing with re
      epithelialization within 1 year of follow-up. The trial was stopped after 38
      patients were enrolled (17 in the MA group and 21 in the AS group) because of
      marked differences in response. Study groups were comparable in baseline
      characteristics. Cure rates were 0/21 in the AS group compared with 8/17 (47%,
      95% confidence interval: 23-71%) in the MA group (P < 0.001). Side effects and
      laboratory abnormalities were mild in both groups. We conclude that parenteral AS
      given on its own is not effective for MCL in Peru.

PMID- 17556622
TI  - 17Beta-estradiol increases Leishmania mexicana killing in macrophages from DBA/2
      mice by enhancing production of nitric oxide but not pro-inflammatory cytokines.
AB  - We have previously shown that female DBA/2 mice are significantly more resistant
      to Leishmania mexicana compared with males. Here, we have analyzed the effect of
      17beta-estradiol (E(2)) on function and cytokine production in male and female
      DBA/2 macrophages in vitro. We show that E(2) increases NO production and
      parasite killing in L. mexicana-infected male and female DBA/2 macrophages
      without increasing production of pro-inflammatory cytokines. These data indicate
      that E(2) may enhance leishmanicidal activity in macrophages by directly
      regulating production of NO.

PMID- 17556624
TI  - Use of multiple displacement amplification to increase the detection and
      genotyping of trypanosoma species samples immobilized on FTA filters.
AB  - Whole genome amplification methods are a recently developed tool for amplifying
      DNA from limited template. We report its application in trypanosome infections,
      characterized by low parasitemias. Multiple displacement amplification (MDA)
      amplifies DNA with a simple in vitro step and was evaluated on mouse blood
      samples on FTA filter cards with known numbers of Trypanosoma brucei parasites.
      The data showed a 20-fold increase in the number of PCRs possible per sample,
      using primers diagnostic for the multicopy ribosomal ITS region or 177-bp
      repeats, and a 20-fold increase in sensitivity over nested PCR against a single
      copy microsatellite. Using MDA for microsatellite genotyping caused allele
      dropout at low DNA concentrations, which was overcome by pooling multiple MDA
      reactions. The validity of using MDA was established with samples from Human
      African Trypanosomiasis patients. The use of MDA allows maximal use of finite DNA
      samples and may prove a valuable tool in studies where multiple reactions are
      necessary, such as population genetic analyses.

PMID- 17556625
TI  - Field comparison of immunodiagnostic and parasitological techniques for the
      detection of Schistosomiasis japonica in the People's Republic of China.
AB  - A total of 1,811 individuals from two villages located in the areas of China
      endemic for Schistosoma japonicum were analyzed by the Kato-Katz parasitologic
      examination, indirect hemagglutination assay (IHA), and enzyme-linked
      immunosorbent assay (ELISA). Statistical analysis of the results showed the kappa
      indices ranged from 0.106 to 0.234 between IHA and the stool examination and
      ranged from 0.037 to 0.134 between ELISA and the fecal examination. The
      sensitivity value of the IHA was 83.7% in Village A and 92.3% in Village B; the
      specificity value of the IHA was 55.8% in Village A and 67.3% in Village B. The
      sensitivity value of the ELISA was 88.4% in Village A and 96.2% in Village B; the
      specificity value of the ELISA was 38.4% in both Village A and Village B. A
      search for a good diagnostic test that can be applied in field situations in
      China should be given high priority.

PMID- 17556626
TI  - Epidemiology of toxocariasis in a steppe environment: the Patagonia study.
AB  - To investigate the epidemiology of human toxocariasis in a steppe environment, a
      field survey was carried out in three provinces of Argentina's Patagonia (Chubut,
      Neuquen, and Rio Negro) among 114 rural subjects residing in estancias (cattle-
      or sheep-breeding ranches). Overall seroprevalence was 31.6%, and the
      contamination rate of soil by Toxocara eggs was 35.1%. Bivariate and multivariate
      analyses were performed for various exposure variables and also for the De
      Martonne aridity-humidity index. Multivariate analysis revealed that the
      seroprevalence rate was found to be inversely correlated with age but was
      positively linked to De Martonne index. These findings suggest that the harsh
      climatic conditions existing in Argentina's Patagonia would inhibit embryonation
      of eggs in the soil, thus lowering the transmission of human toxocariasis.

PMID- 17556627
TI  - Acute respiratory distress syndrome in scrub typhus.
AB  - Scrub typhus is a mite-borne infectious disease caused by Orientia tsutsugamushi.
      Acute respiratory distress syndrome (ARDS) is a serious complication of scrub
      typhus. This study retrospectively reviewed the medical records of 72 patients
      diagnosed with scrub typhus from January 1998 to August 2006 in Kaohsiung Chang
      Gung Memorial Hospital in Taiwan. Eight of 72 scrub typhus patients with ARDS
      were included in the study; the other patients without ARDS were used as
      controls. The mortality rate for the scrub typhus patients with ARDS was 25%. The
      eight patients seldom had underlying diseases. Initial presentations of dyspnea
      and cough, white blood cell count, hematocrit, total bilirubin, and delayed used
      of appropriate antibiotics use were significant predictors of ARDS. Multivariate
      analysis showed that albumin, prothrombin time, and delayed use of appropriate
      antibiotics were independent predictors of ARDS. Identification of these relative
      risk factors may help clinicians evaluate clinical cases of scrub typhus with
      ARDS.

PMID- 17556629
TI  - Factors associated with E. coli contamination of household drinking water among
      tsunami and earthquake survivors, Indonesia.
AB  - The December 2004 tsunami in Sumatra, Indonesia, destroyed drinking water
      infrastructure, placing over 500,000 displaced persons at increased risk of
      waterborne disease. In June 2005, we assessed the relationship of water handling
      behaviors to household water quality in three districts: Aceh Besar, Simeulue,
      and Nias. We surveyed 1,127 households from 21 communities and tested stored
      drinking water. Factors associated with a reduced likelihood of having
      contaminated stored drinking water included obtaining water from improved sources
      (Aceh Besar, adjusted odds ratio (aOR) 0.41, P < 0.01; Simeulue, aOR 0.48, P =
      0.02), using chlorine solution (Simeulue, aOR 0.41, P < 0.01), and having free
      chlorine in stored water (Aceh Besar, aOR 0.42, P < 0.01; Nias, aOR 0.28, P <
      0.01). Reported boiling, even among those who could describe correct practice,
      was not associated with improved water quality. Water source improvement and
      household water chlorination appear to be useful strategies to improve household
      stored drinking water quality in post-disaster situations.

PMID- 17556628
TI  - Pharmacokinetics of azithromycin and the combination of ivermectin and
      albendazole when administered alone and concurrently in healthy volunteers.
AB  - Azithromycin is a critical component of an integrated disease elimination program
      against trachoma. This study was conducted to evaluate whether azithromycin has a
      pharmacokinetic interaction with the combination of ivermectin and albendazole.
      Eighteen healthy volunteers were administered single doses of azithromycin,
      ivermectin/albendazole, and the combination of the three agents in random,
      crossover fashion. To assess the presence of interactions, test (combination) and
      reference (single dose) data were compared using an estimation approach. Compared
      with reference phases, the geometric mean values for the combination arm's
      azithromycin AUC(0-t) and C(max) were increased approximately 13% and 20%,
      respectively, albendazole AUC(0-t) decreased by approximately 3% and C(max)
      increased approximately 3%, and ivermectin AUC(0-t) and C(max) were increased 31%
      and 27%, respectively. Albendazole sulfoxide AUC(0-t) and C(max) were decreased
      approximately 16% and 14%, respectively. All treatments were well tolerated. The
      interactions for azithromycin and albendazole were minimal although the increase
      in ivermectin exposure requires further study.

PMID- 17556630
TI  - Emergence of Shiga toxin 1 genes within Shigella dysenteriae type 4 isolates from
      travelers returning from the Island of Hispanola.
AB  - Shiga toxins are produced by Shigella dysenteriae type 1 and certain strains of
      Escherichia coli. Three cases of Shiga toxin-producing S. dysenteriae type 4 were
      identified among travelers to the island of Hispanola between 2002 and 2005.
      Clinical and public health practitioners should be aware of this newly identified
      strain.

PMID- 17556631
TI  - A cluster-randomized controlled trial evaluating the effect of a handwashing
      promotion program in Chinese primary schools.
AB  - Intensive handwashing promotion can reduce diarrheal and respiratory disease
      incidence. To determine whether less intensive, more scalable interventions can
      improve health, we evaluated a school-based handwashing program. We randomized 87
      Chinese schools to usual practices: standard intervention (handwashing program)
      or expanded intervention (handwashing program, soap for school sinks, and peer
      hygiene monitors). We compared student absence rates, adjusting for cluster
      design. In control schools, children experienced a median 2.0 episodes (median
      2.6 days) of absence per 100 student-weeks. In standard intervention schools,
      there were a median 1.2 episodes (P = 0.08) and 1.9 days (P = 0.14) of absence
      per 100 student-weeks. Children in expanded intervention schools experienced a
      median 1.2 episodes (P = 0.03) and 1.2 days (P = 0.03) of absence per 100 student
      weeks. Provision of a large-scale handwashing promotion program and soap was
      associated with significantly reduced absenteeism. Similar programs could improve
      the health of children worldwide.

PMID- 17556632
TI  - Clonal reconquest of antibiotic-susceptible Salmonella enterica serotype Typhi in
      Son La Province, Vietnam.
AB  - In the last three decades, high rates of resistance to common first-line
      antimicrobial agents have been reported in Salmonella enterica serotype Typhi
      (Typhi), the causative organism of typhoid fever (TF), in many regions of the
      world, especially in South East Asia. Analysis of Typhi strains isolated from
      outbreaks and sporadic cases of TF in Son La province, northwest Vietnam, in 2002
      revealed that 94.5% (85/90) of the isolates were fully susceptible to
      amoxicillin, chloramphenicol, cotrimoxazole, tetracycline, and nalidixic acid.
      There was a clear decline in the occurrence of multi-drug resistant (MDR) Typhi
      isolates collected in this province in 2002 (4.4%) compared with the period 1995
      1999 in the same province (30.8-100%). By using molecular (IS200 profiling, PstI
      ribotyping, XbaI-pulsed-field gel electrophoresis, and haplotyping) and phage
      typing methods, we showed that the Typhi isolates from Son La province in 2002
      were genetically related; however, they were unrelated to the previous MDR clones
      established in Vietnam.

PMID- 17556633
TI  - An outbreak of dengue virus serotype 1 infection in Cixi, Ningbo, People's
      Republic of China, 2004, associated with a traveler from Thailand and high
      density of Aedes albopictus.
AB  - Autochthonous dengue infections have not been reported in Ningbo, People's
      Republic of China since 1929. In August-October 2004, an outbreak of dengue fever
      was confirmed in Xiaolin, Cixi, Ningbo. Of 83 cases reported, 68 were laboratory
      confirmed. Fifty-three percent (34 of 64) of the cases had IgM antibodies to
      dengue virus. Dengue virus serotype-1 was isolated from two cases. The outbreak
      was linked to a traveler who returned from Thailand. Phylogenetic analysis showed
      that the Ningbo isolate was closely associated to strains from Thailand.
      Prevalence of dengue-specific IgG in asymptomatic residents was significantly
      higher in the epidemic-stricken area than in a control area. High density of
      Aedes albopictus, which resulted from waterlogging caused by Typhoon Rananim and
      lifestyle of local residents, was responsible for rapid spread of the virus.
      Eradication of mosquito infestation might interrupt transmission. This outbreak
      underscores the importance of maintaining surveillance and control of potential
      vectors for the control of emerging infectious diseases.

PMID- 17556634
TI  - Seroprevalence of Chikungunya virus infection on Grande Comore Island, union of
      the Comoros, 2005.
AB  - An outbreak of Chikungunya virus (CHIKV) illness associated with high fever
      combined with prolonged and severe arthralgias occurred on Grande Comore Island
      from January through May 2005; 5,202 cases were reported. A seroprevalence study
      was conducted to define the extent of transmission on the island. We conducted a
      cross-sectional survey using a multistage sampling technique. A total of 481
      households were sampled. In each household, one resident was selected randomly
      for interview and blood collection. We administered questionnaires and tested 331
      sera for CHIKV-specific IgM and IgG antibodies by capture enzyme-linked
      immunosorbent assay. Infection with CHIKV infection (seropositivity) was defined
      as presence of IgG and/or IgM antibodies to CHIKV. A total of 331 (69%) of 481
      survey participants consented to blood collection. Antibodies to CHIKV were
      detected in 63% of sera; IgM antibodies were found in 60% of specimens and IgG
      antibodies were detected in 27% of specimens. Extrapolation of the findings to
      the entire Grande Comore population suggested that nearly 215,000 people were
      infected with CHIKV during the outbreak. A total of 79% of the seropositive
      persons were hospitalized or stayed at home in bed for a mean of 6 days (range =
      1-30 days); 52% missed work or school for a mean of 7 days (range = 1-40 days).
      The findings suggest that CHIKV was broadly transmitted during the outbreak with
      a high attack rate. Although not fatal during this outbreak, CHIKV infection
      caused significant morbidity and decreased economic productivity.

PMID- 17556635
TI  - Antigenic and genetic relationships among Rift Valley fever virus and other
      selected members of the genus Phlebovirus (Bunyaviridae).
AB  - Preliminary serologic data indicated that two South American phleboviruses
      (Belterra virus [BELTV] and Icoaraci virus [ICOV]) may be related to Rift Valley
      fever virus (RVFV), an African phlebovirus that causes severe hepatitis and
      hemorrhagic fever in humans. To further define this relationship and to
      investigate the underlying genetic basis, comparative serologic and genetic
      sequence analyses were performed with RVFV and five other New World phleboviruses
      (ICOV, BELTV, Salobo virus, Joa virus, and Frijoles virus). Serologically, a one
      way cross reaction was confirmed between antibodies against these New World
      viruses and RVFV antigen. In contrast, phylogenetic analysis demonstrated clear
      separation of these viruses from RVFV, into distinct phylogenies, based on
      sequences of the small, medium, and large RNA segments.

PMID- 17556636
TI  - The metabolism and toxicity of furosemide in the Wistar rat and CD-1 mouse: a
      chemical and biochemical definition of the toxicophore.
AB  - Furosemide, a loop diuretic, causes hepatic necrosis in mice. Previous evidence
      suggested hepatotoxicity arises from metabolic bioactivation to a chemically
      reactive metabolite that binds to hepatic proteins. To define the nature of the
      toxic metabolite, we examined the relationship between furosemide metabolism in
      CD-1 mice and Wistar rats. Furosemide (1.21 mmol/kg) was shown to cause toxicity
      in mice, but not rats, at 24 h, without resulting in glutathione depletion. In
      vivo covalent binding to hepatic protein was 6-fold higher in the mouse (1.57 +/-
      0.98 nmol equivalent bound/mg protein) than rat (0.26 +/- 0.13 nmol equivalent
      bound/mg protein). In vivo covalent binding to mouse hepatic protein was reduced
      14-fold by a predose of the cytochrome P450 (P450) inhibitor, 1
      aminobenzotriazole (ABT; 0.11 +/- 0.04 nmol equivalent bound/mg protein), which
      also reduced hepatotoxicity. Administration of [(14)C]furosemide to bile duct
      cannulated rats demonstrated turnover to glutathione conjugate (8.8 +/- 2.8%),
      gamma-ketocarboxylic acid metabolite (22.1 +/- 3.3%), N-dealkylated metabolite
      (21.1 +/- 2.9%), and furosemide glucuronide (12.8 +/- 1.8%). Furosemide
      glutathione conjugate was not observed in bile from mice dosed with
      [(14)C]furosemide. The novel gamma-ketocarboxylic acid, identified by nuclear
      magnetic resonance spectroscopy, indicates bioactivation of the furan ring.
      Formation of gamma-ketocarboxylic acid was P450-dependent. In mouse liver
      microsomes, a gamma-ketoenal furosemide metabolite was trapped, forming an N
      acetylcysteine/N-acetyl lysine furosemide adduct. Furosemide (1 mM, 6 h) became
      irreversibly bound to primary mouse and rat hepatocytes, 0.73 +/- 0.1 and 2.44 +/
      0.3 nmol equivalent bound/mg protein, respectively, which was significantly
      reduced in the presence of ABT, 0.11 +/- 0.03 and 0.21 +/- 0.1 nmol equivalent
      bound/mg protein, respectively. Furan rings are part of new chemical entities,
      and mechanisms underlying species differences in toxicity are important to
      understand to decrease the drug attrition rate.

PMID- 17556637
TI  - Role of N-methyl-D-aspartate receptors in antidepressant-like effects of sigma 1
      receptor agonist 1-(3,4-dimethoxyphenethyl)-4-(3-phenylpropyl)piperazine
      dihydrochloride (SA-4503) in olfactory bulbectomized rats.
AB  - In the present study, we aimed to investigate the role of N-methyl-D-aspartate
      (NMDA) receptors in the antidepressant-like effects of a sigma(1) receptor
      agonist, 1-(3,4-dimethoxyphenethyl)-4-(3-phenylpropyl)piperazine dihydrochloride
      (SA-4503), in the olfactory bulbectomized (OB) rat model of depression. A
      symptomatology-based behavioral investigation was made by reconstructing in OB
      rats the symptoms of depression, such as psychomotor agitation, loss of interest,
      and cognitive dysfunction, using a typical antidepressant, desipramine, as a
      positive control. Repeated treatment with SA-4503 ameliorated the behavioral
      deficits in OB rats resembling depression symptoms in the open-field test, sexual
      behavior test, and cued and contextual fear-conditioning test. SA-4503 displayed
      advantages over desipramine in the sexual behavior test. SA-4503 also reversed
      the decrease in the protein expression of NMDA receptor subunit (NR)1, but not
      NR2A or NR2B, in the prefrontal cortex, hippocampus, and amygdala of OB rats. The
      behavioral and neurochemical effects of SA-4503 were blocked by combined
      treatment with a specific sigma(1) receptor antagonist, N,N-dipropyl-2-(4-methoxy
      3-(2-phenylethoxy)phenyl)ethylamine monohydrochloride (NE-100). Furthermore, the
      effects of SA-4503 on the performance of OB rats in the behavioral tests were
      abrogated by acute treatment with an NMDA receptor antagonist, (-)-5-methyl-10,11
      dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate (MK-801). The present study
      indicated for the first time that the sigma(1) receptor agonist SA-4503 may have
      effects on depressive symptoms such as agitation, loss of interest, and impaired
      cognition, which are mediated by NMDA receptors.

PMID- 17556638
TI  - Involvement of rat and human organic anion transporter 3 in the renal tubular
      secretion of topotecan [(S)-9-dimethylaminomethyl-10-hydroxy-camptothecin
      hydrochloride].
AB  - Topotecan [(S)-9-dimethylaminomethyl-10-hydroxy-camptothecin hydrochloride] is
      primarily excreted into urine in humans, with approximately 49% of the dose
      recovered as total topotecan (topotecan lactone plus topotecan hydroxyl acid
      form). The renal elimination of topotecan involves tubular secretion in addition
      to glomerular filtration, but little is known about the molecular mechanism of
      the renal tubular secretion. In the present study, we investigated the transport
      characteristics of topotecan hydroxyl acid across the renal basolateral membrane
      using rat kidney slices and rat or human transporter-expressing Xenopus laevis
      oocytes. Pravastatin and probenecid significantly inhibited the uptake of
      topotecan hydroxyl acid by rat kidney slices with K(i) values of 10.6 and 8.1
      microM, respectively, and p-aminohippurate was weakly inhibitory at high
      concentrations, whereas excess tetraethylammonium had no effect. The uptake of
      topotecan hydroxyl acid by oocytes injected with complementary RNA of either rat
      or human organic anion transporter 3 (rOAT3 or hOAT3) was greater than that of
      water-injected oocytes. Kinetic analysis showed that the K(m) values for rOAT3
      and hOAT3 were 21.9 and 56.5 microM, respectively. Neither rOAT1 nor hOAT1
      stimulated topotecan hydroxyl acid transport. These results suggest that the
      urinary excretion of topotecan hydroxyl acid is accounted for by transport via
      OAT3, as well as glomerular filtration, in both rats and humans; therefore, drug
      drug interactions involving OAT3 may cause a change in clearance of topotecan.

PMID- 17556639
TI  - Cardiovascular diseases and decline in cognitive function in an elderly community
      population: the Edinburgh Artery Study.
AB  - OBJECTIVE: To investigate cognitive performance and 4-year change in cognitive
      function in relation to different clinical manifestations of atherosclerotic
      disease in an elderly community population. METHODS: The Edinburgh Artery Study
      is a population cohort study of men and women who were recruited to a baseline
      survey in 1987 and 1988. From the time of study entry, the participants have been
      invited to two follow-up clinical examinations and continuously monitored for
      major fatal and nonfatal vascular events. All alive and eligible subjects were
      invited for cognitive testing in two study years when the mean age of the sample
      was 73.1 (standard deviation = 5.0) years. A follow-up cognitive assessment was
      performed in 2002 and 2003 on 452 survivors. RESULTS: In multivariate analyses
      controlling for demographic characteristics, depression, and major
      atherosclerotic risk factors, stroke was associated with a significantly worse
      performance on tests of verbal memory (p = .02) and letter fluency (p = .002). In
      addition, stroke was related to a significantly steeper 4-year decline in verbal
      memory performance (p = .04). Among the subjects who had not had an overt stroke,
      those with symptomatic peripheral arterial disease experienced a significantly
      greater 4-year decline in verbal memory functioning (p = .04). CONCLUSIONS: In
      older people, stroke is associated with both worse performance on cognitive tests
      and progressive verbal memory decline. Elderly individuals with vascular diseases
      other than stroke may also be vulnerable to a greater decline in verbal memory
      function. A relationship between vascular diseases and verbal memory decline may
      exist independently of depressed mood and major atherosclerotic risk factors.

PMID- 17556640
TI  - Frailty is associated with incident Alzheimer's disease and cognitive decline in
      the elderly.
AB  - OBJECTIVE: To assess the association between frailty and incident Alzheimer's
      disease (AD) and cognitive decline. Frailty is common in older persons and
      associated with adverse health outcomes. METHODS: Study subjects included 823
      older persons without dementia who participated in the Rush Memory and Aging
      Project, a longitudinal study of aging, and underwent annual assessments of
      frailty, cognition, and diagnostic evaluation for AD. RESULTS: During a 3-year
      follow-up, 89 of 823 participants developed AD. In a proportional hazards model,
      both baseline level of frailty and annual rate of change in frailty were
      associated with an increased risk of incident AD. Each additional one tenth of a
      unit increase on the frailty scale at baseline was associated with >9% increased
      risk of AD (hazard ratio: 2.44; 95% confidence interval (CI): 1.49, 3.37); each
      one tenth of a unit increase in annual rate of change in frailty was associated
      with a 12% increased risk of AD (hazard ratio: 3.30; 95% CI: 1.52, 7.13). These
      results were unchanged in analyses controlling for vascular risk factors and
      vascular diseases. Results were similar with a categorical measure of frailty
      instead of a continuous measure. Further, linear mixed-effects models showed that
      the level of and rate of change in frailty were also associated with the rate of
      cognitive decline. CONCLUSION: Increasing frailty is associated with incident AD
      and the rate of cognitive decline in older persons. These findings suggest that
      frailty and AD may share similar etiologies.

PMID- 17556641
TI  - Adherence, reports of benefits, and depression among patients treated with
      continuous positive airway pressure.
AB  - OBJECTIVES: To examine if reported obstructive sleep apnea (OSA) symptom
      improvement, baseline depressive symptoms, or polysomnographically measured sleep
      parameters are associated with adherence to continuous positive airway pressure
      (CPAP). CPAP is a highly effective treatment for OSA. Low adherence to CPAP
      therapy is common and poorly understood. Depression and lack of perceived
      benefits from CPAP are possible reasons for low adherence. METHODS: Seventy-eight
      patients evaluated for OSA at a sleep medicine center agreed to participate in
      the study; 54 patients completed all study assessments. The Beck Depression
      Inventory (BDI) and the functional outcomes of sleep questionnaire (FOSQ) were
      administered before polysomnographic evaluation. A card embedded in the CPAP
      device electronically recorded adherence. The BDI and FOSQ were administered 1 to
      2 months after the baseline measurements were obtained. RESULTS: Baseline
      depressive symptoms were not correlated with mean duration of CPAP use per night.
      Reported improvements in OSA symptoms were correlated positively with CPAP
      adherence. There were significant positive correlations between improvement in
      depressive symptoms and OSA symptoms after initiation of CPAP therapy. The
      polysomnographic variables measured did not predict improvement in daytime OSA
      symptoms or CPAP adherence. Post hoc analyses suggested that those individuals
      with baseline Apnea Hypopnea Index (AHI) between 40 and 80 experienced more
      symptom improvement than those with AHI <40 or >80. CONCLUSIONS: Patients with
      the greatest level of CPAP adherence also reported the greatest improvement in
      OSA symptoms. Patients who continued to experience OSA symptoms after CPAP
      treatment also tended to have more depressive symptoms after CPAP treatment.

PMID- 17556642
TI  - Unfavorable socioeconomic conditions in early life presage expression of
      proinflammatory phenotype in adolescence.
AB  - OBJECTIVE: Unfavorable socioeconomic status (SES) circumstances early in life are
      associated with heightened vulnerability to respiratory and cardiovascular
      diseases in adulthood. However, little is known about mechanisms underlying this
      phenomenon. METHODS: This study examined whether early-life SES predicts future
      activity of two genes involved in regulating inflammation. An ethnically diverse
      cohort of 136 adolescent females was enrolled in the study. SES was measured by
      home ownership. The messenger ribonucleic acid (mRNA) for glucocorticoid receptor
      (GR) and toll-like receptor 4 (TLR4) was quantified in peripheral blood
      leukocytes using real-time reverse transcriptase polymerase chain reaction (RT
      PCR). RESULTS: Three findings emerged: a) Years 2 to 3 of life were a critical
      period: the participants whose families owned homes during these childhood years
      showed higher GR mRNA and lower TLR4 mRNA during adolescence, a profile that
      suggests better regulation of inflammatory responses. b) These effects were not
      mediated through current economic circumstances, life stress, or health
      practices. C) Changes in SES during later years were unable to "undo" these
      effects. CONCLUSIONS: These findings suggest that unfavorable SES circumstances
      in the early years of life presage the expression of a proinflammatory phenotype
      in adolescence. To the extent that this proclivity toward inflammation persists
      over one's lifespan it could explain the heightened incidence of respiratory and
      cardiovascular disease in low SES populations.

PMID- 17556644
TI  - Relationship between anxiety and gastric sensorimotor function in functional
      dyspepsia.
AB  - OBJECTIVE: To investigate the relationship between anxiety and gastric
      sensorimotor function in patients with (hypersensitive) functional dyspepsia
      (FD). Comorbidity between FD and anxiety disorders is high. In FD, epigastric
      pain is associated with gastric hypersensitivity and neuroticism, a personality
      trait related to anxiety. Experimentally induced anxiety in healthy volunteers is
      associated with changes in sensorimotor function of the proximal stomach.
      METHODS: A total of 139 patients with FD (n = 102 women) underwent a barostat
      investigation to determine gastric compliance, meal accommodation, and thresholds
      for discomfort and pain. Anxiety was measured by the State-Trait Anxiety
      Inventory (STAI) scale (anxiety as a stable personality trait) and the STAI-State
      scale (momentary anxiety). The anxiety subscale of the Hospital Anxiety and
      Depression Scale (HADS-A) was filled out to detect comorbid anxiety disorders.
      RESULTS: Hyper- and normosensitive patients had similar anxiety scores, but
      gastric compliance was significantly lower in hypersensitive patients (11.4
      versus 32.8 ml/mm Hg; p < .001). In the whole patient group, no significant
      correlations between STAI scores and gastric sensorimotor function were found. In
      hypersensitive patients (n = 53, 43 women), state anxiety was negatively
      correlated with discomfort threshold (rho = -.49; p = .001), pain threshold (rho
      = -.48; p = .02), and gastric compliance (rho = -.46; p = .002). These results
      were confirmed by multiple linear and logistic regression analyses. CONCLUSION:
      In hypersensitive patients with FD, state anxiety is significantly and negatively
      correlated with discomfort threshold, pain threshold, and compliance. These
      results strengthen the hypothesis that anxiety is important in FD, especially in
      hypersensitive patients.

PMID- 17556643
TI  - Persistent depressive symptoms and functional decline among patients with
      peripheral arterial disease.
AB  - OBJECTIVE: Because depressive symptoms are prevalent among patients with
      peripheral arterial disease (PAD), our goal was to study the effect of depressive
      symptoms over time on functional decline among patients with PAD. METHODS: We
      conducted a prospective cohort study of 417 patients with PAD followed annually
      for 2 years. A Geriatric Depression Scale Short Form (GDS-S) score >5 was
      considered positive for depressive symptoms. Depressive symptom categories based
      on annual GDS-S measures included persistent, new, resolved, and no depressive
      symptoms. Outcome variables were change in 6-minute walk distance, 4-meter fast
      walking velocity, and short physical performance battery (0-12 scale, 12 = best).
      Results are adjusted for age, sex, race, body mass index, marital status,
      exercise level, smoking, ankle brachial index, leg symptoms, comorbidities, beta
      blocker medication use, anti-depressant medications, and interim medical events.
      RESULTS: In adjusted analyses, patients with new depressive symptoms had greater
      annual decline in fast walking velocity compared with that of patients with no
      depressive symptoms (-0.08 versus -0.01 meters/second per year, p = .02).
      Patients with persistent depressive symptoms had greater annual decline in 6
      minute walk distance (-86.4 versus -41.5 feet/yr, p = .04), fast walking velocity
      (-0.08 versus -0.01 meters/second per year, p = .004), and short physical
      performance battery (-0.73 versus -0.18 per year, p = .005) compared with that of
      patients with no depressive symptoms. CONCLUSIONS: Among patients with PAD,
      persistent and new depressive symptoms are associated with greater annual decline
      in functional performance. Further study is needed to determine the mechanisms of
      these associations and whether treatment of depressive symptoms prevents
      functional decline in persons with PAD.

PMID- 17556645
TI  - Disaster-related posttraumatic stress disorder and physical health.
AB  - OBJECTIVE: To examine the relationship between posttraumatic stress disorder
      (PTSD) and self-reported as well as physician-recorded physical health in a
      sample of survivors (n = 896) of a man-made disaster, using a longitudinal design
      that included predisaster health data. Most studies on the relationship between
      PTSD and physical health are cross-sectional and use self-reported physical
      health outcomes. METHODS: A surveillance using the electronic medical records of
      survivors' family practitioners (FPs), 1 year predisaster until 4 years
      postdisaster, was combined with a survey, 3 weeks and 18 months postdisaster.
      Self-reported PTSD and self-reported physical health were assessed at 18 months
      postdisaster. FP-recorded physical health problems in the subsequent 2 years were
      classified according to the International Classification of Primary Care.
      Multiple regression analyses were used to describe the relationships between PTSD
      and physical health. RESULTS: After adjusting for demographics, smoking behavior,
      and predisaster physical health, PTSD was significantly associated with FP
      recorded vascular, musculoskeletal, and dermatological problems, and with all
      self-reported physical health aspects. Prospectively, PTSD signaled an increased
      risk of new vascular problems (odds ratio = 1.92; 1.04-3.55). CONCLUSIONS: This
      study suggests an effect of PTSD in the development of vascular problems. The
      results imply that clinicians should be alert that disaster survivors with PTSD
      can suffer from comorbid medical problems as well.

PMID- 17556646
TI  - Quantification of hemoglobin A2 by tandem mass spectrometry.
AB  - BACKGROUND: Peptide-based analysis of whole blood using electrospray tandem mass
      spectrometry (MSMS) in multiple reaction monitoring (MRM) mode enables rapid
      detection and sequence confirmation of clinically significant hemoglobin (Hb)
      variants. We applied a similar, quantitative approach to the measurement of
      delta:beta-globin peptide ratios as potential surrogate markers of HbA(2), a
      biomarker used in population screening for beta-thalassemia trait. METHODS: We
      studied 163 blood samples with normal HbA(2) (%), 105 with increased HbA(2), 43
      with delta-chain variants, and 8 with Hb Lepore. All were tested by HPLC. The
      samples were also incubated with trypsin for 30 min at 37 degrees C for MSMS with
      flow injection analysis. MRMs for the delta- (T2, T3, and T14) and beta- (T2, T3,
      and T13) globin tryptic peptides were acquired for 1 min, and delta:beta peptide
      ratios were calculated. We used HPLC and MSMS to analyze 26 paired whole blood
      and dried blood spot samples after storage for 1, 8, and 29 days. RESULTS: Within
      and between-assay imprecision values (CVs) were <6.1% and <8.4%, respectively,
      for the delta:beta peptide ratios. Digests were stable at 10 degrees C for 6
      days. Significant correlations (P <0.0001) between MSMS delta:beta-globin peptide
      ratios and HPLC HbA(2) allowed differentiation between increased HbA(2)
      concentrations and concentrations within the reference interval and
      identification of Hb Lepore. This differentiation was repeatable by MSMS, but not
      by HPLC, after blood spot samples had been stored for 1 month. CONCLUSION: This
      study validates the quantitative delta:beta-globin peptide ratio as a surrogate
      marker of HbA(2) and demonstrates the potential of rapid peptide-based MSMS for
      multiplexed, high-throughput protein biomarker characterization and
      quantification.

PMID- 17556647
TI  - Expanded instrument comparison of amplicon DNA melting analysis for mutation
      scanning and genotyping.
AB  - BACKGROUND: Additional instruments have become available since instruments for
      DNA melting analysis of PCR products for genotyping and mutation scanning were
      compared. We assessed the performance of these new instruments for genotyping and
      scanning for mutations. METHODS: A 110-bp fragment of the beta-globin gene
      including the sickle cell anemia locus (HBB c. 20A>T) was amplified by PCR in the
      presence of LCGreen Plus or SYBR Green I. Amplicons of 4 different genotypes
      [wild-type, homozygous, and heterozygous HBB c. 20A>T and double-heterozygote HBB
      c. (9C>T; 20A>T)] were melted on 7 different instruments [Applied Biosystems
      7300, Corbett Life Sciences Rotor-Gene 6500HRM, Eppendorf Mastercycler
      RealPlex4S, Idaho Technology LightScanner (384 well), Roche LightCycler 480 (96
      and 384 well) and Stratagene Mx3005p] at a rate of 0.61 degrees C/s or when this
      was not possible, at 0.50 degrees C steps. We evaluated the ability of each
      instrument to genotype by melting temperature (Tm) and to scan for heterozygotes
      by curve shape. RESULTS: The ability of most instruments to accurately genotype
      single-base changes by amplicon melting was limited by spatial temperature
      variation across the plate (SD of Tm = 0.020 to 0.264 degrees C). Other variables
      such as data density, signal-to-noise ratio, and melting rate also affected
      heterozygote scanning. CONCLUSIONS: Different instruments vary widely in their
      ability to genotype homozygous variants and scan for heterozygotes by whole
      amplicon melting analysis. Instruments specifically designed for high-resolution
      melting, however, displayed the least variation, suggesting better genotyping
      accuracy and scanning sensitivity and specificity.

PMID- 17556649
TI  - Multiple fluorescent labeling of silica nanoparticles with lanthanide chelates
      for highly sensitive time-resolved immunofluorometric assays.
AB  - BACKGROUND: Time-resolved immunofluorometric assays (TrIFA) using lanthanide
      labeled nanoparticles have greatly increased the sensitivity of immunoassays.
      Current labeling strategies, however, use either physical doping of lanthanide
      chelates into preformed nanoparticles or covalent linking of lanthanide chelates
      to precursors used for making nanoparticles; both these strategies have
      drawbacks. METHODS: Luminescent Eu(III) and Tb(III) chelates were covalently
      coated on the surface of preformed silica nanoparticles to which detection
      antibodies or bridging proteins for antibody binding were conjugated. We used the
      resulting conjugates in TrIFA for detection of hepatitis B surface antigen
      (HBsAg) and hepatitis B e antigen (HBeAg), both individually and simultaneously.
      We compared the results of the newly established method with results of an ELISA
      for serum samples. Positive samples identified by TrIFA but not by ELISA were
      confirmed by additional assays, including real-time PCR detection of viral DNA.
      RESULTS: The prepared nanoparticle conjugates were homogeneous in size, at
      approximately 55 (5) nm in diameter [mean (SD)], were stable for long-time
      storage (>2 years), and contained more chelates [6.86 x 10(5) for Eu(III), 4.73 x
      10(4) for Tb(III)] per nanoparticle than particles made as previously reported.
      The TrIFA established for HBsAg had a comparable or lower detection limit (0.0092
      microg/L) than existing nanoparticle-based TrIFA or ELISA. The TrIFA for HBeAg
      had a much lower detection limit [10.0 National Centre Unit (NCU)/L] than ELISA
      and detected HBeAg in 5 samples missed by the ELISA method. Simultaneous TrIFA
      for both HBsAg and HBeAg was achieved with detection limits (0.033 microg/L for
      HBsAg and 27.0 NCU/L for HBeAg) close to those of the individual assays.
      CONCLUSIONS: Covalent surface labeling of silica nanoparticles with lanthanide
      chelates provides good fluorescent labels that can be used in TrIFA for highly
      sensitive and robust detection of clinical targets.

PMID- 17556650
TI  - Effect of aging, MnSOD deficiency, and genetic background on endothelial
      function: evidence for MnSOD haploinsufficiency.
AB  - OBJECTIVE: The goal of this study was to compare vascular function, superoxide
      levels, and MnSOD protein expression in young (4 to 7 months) and old (22 to 24
      months) MnSOD+/+ and MnSOD-deficient (MnSOD+/-) mice. METHODS AND RESULTS:
      Relaxation of aorta in vitro to the endothelium-dependent dilator acetylcholine
      (ACh) was similar in young MnSOD+/+ (n=9) and young MnSOD+/- (n=6) mice. This
      response was impaired in old MnSOD+/+ (n=8) mice and old MnSOD+/- mice (n=14),
      with dysfunction being greater in old MnSOD-deficient mice (eg, 100 micromol/L
      ACh produced 77+/-3% [mean+/-SE], 77+/-3%, 70+/-4%, and 57+/-4% relaxation in
      young MnSOD+/+, young MnSOD+/-, old MnSOD+/+, and old MnSOD+/- mice,
      respectively). The endothelial dysfunction was similar in mice on both C57BL/6
      and CD-1 genetic backgrounds. In contrast to ACh, responses to the endothelium
      independent dilator sodium nitroprusside were enhanced in old MnSOD+/+ and
      MnSOD+/- mice compared with both groups of young mice (P<0.05). Superoxide
      levels, as measured using lucigenin-enhanced chemiluminescence, were increased
      more than 2-fold in old MnSOD+/- mice compared with old MnSOD+/+ and young mice
      (P<0.05). CONCLUSIONS: These data provide the first direct evidence that MnSOD
      haploinsufficiency results in increased vascular oxidative stress and endothelial
      dysfunction with aging.

PMID- 17556651
TI  - Endothelial nitric oxide synthase activity is essential for vasodilation during
      blood flow recovery but not for arteriogenesis.
AB  - OBJECTIVE: Arteriogenesis is the major mechanism of vascular growth, which is
      able to compensate for blood flow deficiency after arterial occlusion.
      Endothelial nitric oxide synthase (eNOS) activity is essential for
      neovascularization, however its specific role in arteriogenesis remains unclear.
      We studied the role of eNOS in arteriogenesis using 3 mouse strains with
      different eNOS expression. METHODS AND RESULTS: Distal femoral artery ligation
      was performed in eNOS-overexpressing mice (eNOStg), eNOS-deficient (eNOS-/-)
      mice, and wild type (WT) controls. Tissue perfusion and collateral-dependent
      blood flow were significantly increased in eNOStg mice compared with WT only
      immediately after ligation. In eNOS-/- mice, although tissue perfusion remained
      significantly decreased, collateral-dependent blood flow was only decreased until
      day 7, suggesting normal, perhaps delayed collateral growth. Histology confirmed
      no differences in collateral arteries of eNOStg, eNOS-/-, and WT mice at 1 and 3
      weeks. Administration of an NO donor induced vasodilation in collateral arteries
      of eNOS-/- mice, but not in WT, identifying the inability to vasodilate
      collateral arteries as main cause of impaired blood flow recovery in eNOS-/-
      mice. CONCLUSIONS: This study demonstrates that eNOS activity is crucial for NO
      mediated vasodilation of peripheral collateral vessels after arterial occlusion
      but not for collateral artery growth.

PMID- 17556652
TI  - RhoA activation contributes to sex differences in vascular contractions.
AB  - OBJECTIVE: Studies have suggested that sex differences in endothelial function in
      part account for the lower incidence of cardiovascular disease in premenopausal
      women compared with men. Less is known about the role of smooth muscle. We
      hypothesized that signaling mechanisms that regulate calcium sensitivity in
      vascular muscle also play a role in determining sex differences in contractile
      function. METHODS AND RESULTS: In aorta, concentration-dependent contractions to
      serotonin were greater in male versus female mice whereas contractions to KCl and
      U46619 were similar. Nitric oxide or other endothelial-derived factors did not
      account for the difference in responses to serotonin because inhibition of nitric
      oxide synthase (NOS) with N(G)-nitro-L-arginine, genetic deficiency of
      endothelial NOS, and removal of endothelium increased contractions but did not
      abolish the enhanced contractions in aorta from males. Contractions in aorta from
      both males and females were abolished by a serotonergic 5HT2A receptor antagonist
      (ketanserin), however there was no sex difference in 5HT2A receptor expression.
      Activation of RhoA and Rho-kinase by serotonin was greater in aorta from males
      compared with females, but this was not related to greater expression of RhoA or
      Rho-kinase isoforms (ROCK1 and ROCK2). The sex difference in aortic contractions
      to serotonin was abolished by an inhibitor of Rho-kinase, Y27632. CONCLUSION: We
      conclude that increased contractions to serotonin in aorta from male mice are
      attributable to differences in RhoA/Rho-kinase activation in smooth muscle
      independent of differences in the expression of RhoA or Rho-kinase.

PMID- 17556653
TI  - Interferon-gamma suppresses cyclooxygenase-2 promoter activity by inhibiting C
      Jun and C/EBPbeta binding.
AB  - OBJECTIVE: Cyclooxygenase-2 (COX-2) and interferon gamma (IFNgamma) are
      overexpressed in vascular inflammatory and atherosclerotic lesions. We postulated
      that IFNgamma suppresses COX-2 expression at the transcriptional level. METHODS
      AND RESULTS: The effect of IFNgamma on COX-2 expression was evaluated in several
      types of human cells stimulated with phorbol 12-myristate 13-acetate (PMA),
      interleukin (IL)-1beta, or tumor necrosis factor (TNF) alpha. IFNgamma
      concentration-dependently inhibited COX-2 proteins and promoter activities
      induced by PMA or cytokines in human fibroblasts and monocytic and endothelial
      cells. PMA and cytokines stimulate binding of C-Jun, C-Fos, CCAAT/enhancer
      binding protein beta (C/EBPbeta), or NF-kappaB to their respective regulatory
      elements on COX-2 promoter. IFNgamma blocked C-Jun and C/EBPbeta but not C-Fos or
      p50 NF-kappaB binding as determined by in vitro binding assays and chromatin
      immunoprecipitation assay. p300 binding to COX-2 promoter was inhibited by
      IFNgamma in a manner comparable to C-Jun and C/EBPbeta binding. CONCLUSIONS:
      IFNgamma suppresses proinflammatory mediator-induced COX-2 transcription by
      selective inhibition of C-Jun and C/EBPbeta DNA binding activity and p300
      recruitment in human cells. Because IFNgamma is coexpressed with COX-2 in
      vascular lesions, it may play a role in controlling COX-2-mediated inflammatory
      changes.

PMID- 17556654
TI  - Role of the extrinsic pathway of blood coagulation in hemostasis and thrombosis.
AB  - Hemostasis requires both platelets and the coagulation system. At sites of vessel
      injury, bleeding is minimized by the formation of a hemostatic plug consisting of
      platelets and fibrin. The traditional view of the regulation of blood coagulation
      is that the initiation phase is triggered by the extrinsic pathway, whereas
      amplification requires the intrinsic pathway. The extrinsic pathway consists of
      the transmembrane receptor tissue factor (TF) and plasma factor VII/VIIa
      (FVII/FVIIa), and the intrinsic pathway consists of plasma FXI, FIX, and FVIII.
      Under physiological conditions, TF is constitutively expressed by adventitial
      cells surrounding blood vessels and initiates clotting. In addition so-called
      blood-borne TF in the form of cell-derived microparticles (MPs) and TF expression
      within platelets suggests that TF may play a role in the amplification phase of
      the coagulation cascade. Under pathologic conditions, TF is expressed by
      monocytes, neutrophils, endothelial cells, and platelets, which results in an
      elevation of the levels of circulating TF-positive MPs. TF expression within the
      vasculature likely contributes to thrombosis in a variety of diseases.
      Understanding how the extrinsic pathway of blood coagulation contributes to
      hemostasis and thrombosis may lead to the development of safe and effective
      hemostatic agents and antithrombotic drugs.

PMID- 17556655
TI  - Gene therapy to inhibit the calcium channel beta subunit: physiological
      consequences and pathophysiological effects in models of cardiac hypertrophy.
AB  - Calcium cycling figures prominently in excitation-contraction coupling and in
      various signaling cascades involved in the development of left ventricular
      hypertrophy. We hypothesized that genetic suppression of the L-type calcium
      channel accessory beta-subunit would modulate calcium current and suppress
      cardiac hypertrophy. A short hairpin RNA template sequence capable of mediating
      the knockdown of the L-type calcium channel accessory beta-subunit gene was
      incorporated into a lentiviral vector (PPT.CG.H1.beta(2)). Transduction of
      ventricular myocytes in vivo with the active short hairpin RNA partially
      inhibited the L-type calcium current. In neonatal rat cardiomyocytes, L-type
      calcium channel accessory beta-subunit gene knockdown reduced calcium transient
      amplitude. Similarly, [(3)H]leucine incorporation was attenuated in
      PPT.CG.H1.beta(2)-transduced neonatal rat cardiomyocytes compared with
      nonsilencing controls in a phenylephrine-induced hypertrophy model. In vivo gene
      transfer attenuated the hypertrophic response in an aortic-banded rat model of
      left ventricular hypertrophy, with reduced left ventricular wall thickness and
      heart weight/body weight ratios in PPT.CG.H1.beta(2)-injected rats at four weeks
      post transduction. Fractional shortening was preserved in rats treated with
      PPT.CG.H1.beta(2). These findings indicate that knockdown of L-type calcium
      channel accessory beta-subunit is capable of attenuating the hypertrophic
      response both in vitro and in vivo without compromising systolic performance.
      Suppression of the calcium channel beta subunit may represent a novel and useful
      therapeutic strategy for left ventricular hypertrophy.

PMID- 17556656
TI  - Polyunsaturated fatty acids are cerebral vasodilators via the TREK-1 potassium
      channel.
AB  - Vessel occlusion is the most frequent cause for impairment of local blood flow
      within the brain resulting in neuronal damage and is a leading cause of
      disability and death worldwide. Polyunsaturated fatty acids and especially alpha
      linolenic acid improve brain resistance against cerebral ischemia. The purpose of
      the present study was to evaluate the effects of polyunsaturated fatty acids and
      particularly alpha-linolenic acid on the cerebral blood flow and on the tone of
      vessels that regulate brain perfusion. alpha-Linolenic acid injections increased
      cerebral blood flow and induced vasodilation of the basilar artery but not of the
      carotid artery. The saturated fatty acid palmitic acid did not produce
      vasodilation. This suggested that the target of the polyunsaturated fatty acids
      effect was the TREK-1 potassium channel. We demonstrate the presence of this
      channel in basilar but not in carotid arteries. We show that vasodilations
      induced by the polyunsaturated fatty acid in the basilar artery as well as the
      laser-Doppler flow increase are abolished in TREK-1(-/-) mice. Altogether these
      data indicate that TREK-1 activation elicits a robust dilation that probably
      accounts for the increase of cerebral blood flow induced by polyunsaturated fatty
      acids such as alpha-linolenic acid or docosahexanoic acid. They suggest that the
      selective expression and activation of TREK-1 in brain collaterals could play a
      significant role in the protective mechanisms of polyunsaturated fatty acids
      against stroke by providing residual circulation during ischemia.

PMID- 17556657
TI  - ATP-binding cassette transporter A1 gene transcription is downregulated by
      activator protein 2alpha. Doxazosin inhibits activator protein 2alpha and
      increases high-density lipoprotein biogenesis independent of alpha1-adrenoceptor
      blockade.
AB  - ATP-binding cassette transporter A1 (ABCA1) is a rate-limiting factor for high
      density lipoprotein (HDL) biogenesis. The ABCA1 gene expression is known to be
      upregulated by various transcriptional factors. However, negative regulation
      factors would be better targets for pharmacological modulation of HDL biogenesis.
      Doxazosin, an alpha(1)-adrenoceptor blocker, increased ABCA1 mRNA, its protein,
      and apolipoprotein A-I-mediated HDL biogenesis in THP-1 macrophages and CHO-K1
      cells, independent of alpha(1)-adrenoceptor blockade. Analysis of the human ABCA1
      promoter indicated that the region between the positions -368 and -147 that
      contains an activator protein (AP)2-binding site responsible for the effects of
      doxazosin. Overexpression of AP2alpha inhibited ABCA1 transcription in a dose
      dependent fashion. Mutation in the AP2-binding site caused increase of the basal
      promoter activity and cancelling both the transactivation by doxazosin and the
      trans-repression by AP2alpha. Doxazosin had no effect on ABCA1 mRNA level in
      HepG2 cells, which lack endogenous AP2alpha, and it reversed the inhibitory
      effect of AP2alpha expression in this type of cells. Chromatin
      immunoprecipitation and gel shift assays revealed that doxazosin reduced specific
      binding of AP2alpha to the ABCA1 promoter, as it suppressed phosphorylation of
      AP2alpha. Finally, doxazosin increased ABCA1 expression and plasma HDL in mice.
      We thus concluded that AP2alpha negatively regulates the ABCA1 gene
      transcription. Doxazosin inhibits AP2alpha activity independent of alpha(1)
      adrenoceptor blockade and increases the ABCA1 expression and HDL biogenesis.
      AP2alpha is a potent pharmacological target for the increase of HDL.

PMID- 17556658
TI  - Dilated cardiomyopathy mutant tropomyosin mice develop cardiac dysfunction with
      significantly decreased fractional shortening and myofilament calcium
      sensitivity.
AB  - Mutations in striated muscle alpha-tropomyosin (alpha-TM), an essential thin
      filament protein, cause both dilated cardiomyopathy (DCM) and familial
      hypertrophic cardiomyopathy. Two distinct point mutations within alpha
      tropomyosin are associated with the development of DCM in humans: Glu40Lys and
      Glu54Lys. To investigate the functional consequences of alpha-TM mutations
      associated with DCM, we generated transgenic mice that express mutant alpha-TM
      (Glu54Lys) in the adult heart. Results showed that an increase in transgenic
      protein expression led to a reciprocal decrease in endogenous alpha-TM levels,
      with total myofilament TM protein levels remaining unaltered. Histological and
      morphological analyses revealed development of DCM with progression to heart
      failure and frequently death by 6 months. Echocardiographic analyses confirmed
      the dilated phenotype of the heart with a significant decrease in the left
      ventricular fractional shortening. Work-performing heart analyses showed
      significantly impaired systolic, and diastolic functions and the force
      measurements of cardiac myofibers revealed that the myofilaments had
      significantly decreased Ca(2+) sensitivity and tension generation. Real-time RT
      PCR quantification demonstrated an increased expression of beta-myosin heavy
      chain, brain natriuretic peptide, and skeletal actin and a decreased expression
      of the Ca(2+) handling proteins sarcoplasmic reticulum Ca(2+)-ATPase and
      ryanodine receptor. Furthermore, our study also indicates that the alpha-TM54
      mutation decreases tropomyosin flexibility, which may influence actin binding and
      myofilament Ca(2+) sensitivity. The pathological and physiological phenotypes
      exhibited by these mice are consistent with those seen in human DCM and heart
      failure. As such, this is the first mouse model in which a mutation in a
      sarcomeric thin filament protein, specifically TM, leads to DCM.

PMID- 17556659
TI  - Augmented protein kinase C-alpha-induced myofilament protein phosphorylation
      contributes to myofilament dysfunction in experimental congestive heart failure.
AB  - It is becoming clear that upregulated protein kinase C (PKC) signaling plays a
      role in reduced ventricular myofilament contractility observed in congestive
      heart failure. However, data are scant regarding which PKC isozymes are involved.
      There is evidence that PKC-alpha may be of particular importance. Here, we
      examined PKC-alpha quantity, activity, and signaling to myofilaments in
      chronically remodeled myocytes obtained from rats in either early heart failure
      or end-stage congestive heart failure. Immunoblotting revealed that PKC-alpha
      expression and activation was unaltered in early heart failure but increased in
      end-stage congestive heart failure. Left ventricular myocytes were isolated by
      mechanical homogenization, Triton-skinned, and attached to micropipettes that
      projected from a force transducer and motor. Myofilament function was
      characterized by an active force-[Ca(2+)] relation to obtain Ca(2+)-saturated
      maximal force (F(max)) and myofilament Ca(2+) sensitivity (indexed by EC(50))
      before and after incubation with PKC-alpha, protein phosphatase type 1 (PP1), or
      PP2a. PKC-alpha treatment induced a 30% decline in F(max) and 55% increase in the
      EC(50) in control cells but had no impact on myofilament function in failing
      cells. PP1-mediated dephosphorylation increased F(max) (15%) and decreased EC(50)
      ( approximately 20%) in failing myofilaments but had no effect in control cells.
      PP2a-dependent dephosphorylation had no effect on myofilament function in either
      group. Lastly, PP1 dephosphorylation restored myofilament function in control
      cells hyperphosphorylated with PKC-alpha. Collectively, our results suggest that
      in end-stage congestive heart failure, the myofilament proteins exist in a
      hyperphosphorylated state attributable, in part, to increased activity and
      signaling of PKC-alpha.

PMID- 17556660
TI  - Knock-in mouse model of dilated cardiomyopathy caused by troponin mutation.
AB  - We created knock-in mice in which a deletion of 3 base pairs coding for K210 in
      cardiac troponin (cTn)T found in familial dilated cardiomyopathy patients was
      introduced into endogenous genes. Membrane-permeabilized cardiac muscle fibers
      from mutant mice showed significantly lower Ca(2+) sensitivity in force
      generation than those from wild-type mice. Peak amplitude of Ca(2+) transient in
      cardiomyocytes was increased in mutant mice, and maximum isometric force produced
      by intact cardiac muscle fibers of mutant mice was not significantly different
      from that of wild-type mice, suggesting that Ca(2+) transient was augmented to
      compensate for decreased myofilament Ca(2+) sensitivity. Nevertheless, mutant
      mice developed marked cardiac enlargement, heart failure, and frequent sudden
      death recapitulating the phenotypes of dilated cardiomyopathy patients,
      indicating that global functional defect of the heart attributable to decreased
      myofilament Ca(2+) sensitivity could not be fully compensated by only increasing
      the intracellular Ca(2+) transient. We found that a positive inotropic agent,
      pimobendan, which directly increases myofilament Ca(2+) sensitivity, had profound
      effects of preventing cardiac enlargement, heart failure, and sudden death. These
      results verify the hypothesis that Ca(2+) desensitization of cardiac myofilament
      is the absolute cause of the pathogenesis of dilated cardiomyopathy associated
      with this mutation and strongly suggest that Ca(2+) sensitizers are beneficial
      for the treatment of dilated cardiomyopathy patients affected by sarcomeric
      regulatory protein mutations.

PMID- 17556661
TI  - Yin Yang-1 inhibits vascular smooth muscle cell growth and intimal thickening by
      repressing p21WAF1/Cip1 transcription and p21WAF1/Cip1-Cdk4-cyclin D1 assembly.
AB  - Vascular injury initiates a cascade of phenotype-altering molecular events.
      Transcription factor function in this process, particularly that of negative
      regulators, is poorly understood. We demonstrate here that the forced expression
      of the injury-inducible GLI-Kruppel zinc finger protein Yin Yang-1 (YY1) inhibits
      neointima formation in human, rabbit and rat blood vessels. YY1 inhibits
      p21(WAF1/Cip1) transcription, prevents assembly of a p21(WAF1/Cip1)-cdk4-cyclin
      D1 complex, and blocks downstream pRb(Ser249/Thr252) phosphorylation and
      expression of PCNA and TK-1. Conversely, suppression of endogenous YY1 elevates
      levels of p21(WAF1/Cip1), PCNA, pRb(Ser249/Thr252) and TK-1, and increases
      intimal thickening. YY1 binds Sp1 and prevents its occupancy of a distinct
      element in the p21(WAF1/Cip1) promoter without YY1 itself binding the promoter.
      Additionally, YY1 induces ubiquitination and proteasome-dependent degradation of
      p53, decreasing p53 immunoreactivity in the artery wall. These findings define a
      new role for YY1 as both an inducer of p53 instability in smooth muscle cells,
      and an indirect repressor of p21(WAF1/Cip1) transcription, p21(WAF1/Cip1)-cdk4
      cyclin D1 assembly and intimal thickening.

PMID- 17556662
TI  - Disruption of planar cell polarity signaling results in congenital heart defects
      and cardiomyopathy attributable to early cardiomyocyte disorganization.
AB  - The Drosophila scribble gene regulates apical-basal polarity and is implicated in
      control of cellular architecture and cell growth control. Mutations in mammalian
      Scrib (circletail; Crc mutant) also result in abnormalities suggestive of roles
      in planar cell polarity regulation. We show that Crc mutants develop heart
      malformations and cardiomyopathy attributable to abnormalities in cardiomyocyte
      organization within the early heart tube. N-Cadherin is lost from the
      cardiomyocyte cell membrane and cell-cell adhesion is disrupted. This results in
      abnormalities in heart looping and formation of both the trabeculae and compact
      myocardium, which ultimately results in cardiac misalignment defects and
      ventricular noncompaction. Thus, these late abnormalities arise from defects
      occurring at the earliest stages of heart development. Mislocalization of Vangl2
      in Crc/Crc cardiomyocytes suggests Scrib is acting in the planar cell polarity
      pathway in this tissue. Moreover, double heterozygosity for mutations in both
      Scrib and Vangl2 can cause cardiac defects similar to those found in homozygous
      mutants for each gene but without other major defects. We propose that
      heterozygosity for mutations in different genes in the planar cell polarity
      pathway may be an important mechanism for congenital heart defects and
      cardiomyopathy in humans.

PMID- 17556663
TI  - Innate immune pathway links obesity to insulin resistance.

PMID- 17556664
TI  - LOX-1 and atherosclerosis: proof of concept in LOX-1-knockout mice.

PMID- 17556665
TI  - Resizing the genomic regulation of restenosis.

PMID- 17556666
TI  - Cell-based GATA4 cardiac gene transfer using cell-penetrating peptide.

PMID- 17556667
TI  - The sinoatrial node is still setting the pace 100 years after its discovery.

PMID- 17556668
TI  - The macrophage at the crossroads of insulin resistance and atherosclerosis.
AB  - The macrophage has emerged as an important player in the pathogenesis of both
      atherosclerosis and insulin resistance. Cross-talk between inflammatory
      macrophages and adipocytes may be involved in insulin resistance in peripheral
      tissues. Defective insulin signaling in cells of the arterial wall including
      macrophages may promote the development of atherosclerosis. Insulin resistant
      macrophages are more susceptible to endoplasmic reticulum stress and apoptosis in
      response to various stimuli such as nutrient deprivation, free cholesterol
      loading, and oxidized LDL. Increased apoptosis of insulin resistant macrophages
      and impaired phagocytic clearance of apoptotic cells by insulin resistant
      macrophages in atherosclerotic lesions may lead to enhanced postapoptotic
      necrosis, larger lipid-rich cores, increased inflammation, and more complex
      vulnerable plaques.

PMID- 17556669
TI  - Notch signaling in blood vessels: who is talking to whom about what?
AB  - It has become increasingly clear that the Notch signaling pathway plays a
      critical role in the development and homeostasis of the cardiovascular system.
      This notion has emerged from loss- and gain-of-function analysis and from the
      realization that several hereditary cardiovascular disorders originate from gene
      mutations that have a direct impact on Notch signaling. Current research efforts
      are focused on determining the specific cellular and molecular effects of Notch
      signaling. The rationale for this has stemmed from the clinical importance and
      therapeutic potential of modulating vascular formation during various disease
      states. A more complete appreciation of Notch signaling, as it relates to
      vascular morphogenesis, requires an in-depth knowledge of expression patterns of
      the various signaling components and a comprehensive understanding of downstream
      targets. The goal of this review is to summarize current knowledge regarding
      Notch signaling during vascular development and within the adult vascular wall.
      Our focus is on the genetic analysis and cellular experiments that have been
      performed with Notch ligands, receptors, and downstream targets. We also
      highlight questions and controversies regarding the contribution of this pathway
      to vascular development.

PMID- 17556670
TI  - cAMP and cGMP signaling cross-talk: role of phosphodiesterases and implications
      for cardiac pathophysiology.
AB  - Cyclic nucleotide phosphodiesterases regulate cAMP-mediated signaling by
      controlling intracellular cAMP content. The cAMP-hydrolyzing activity of several
      families of cyclic nucleotide phosphodiesterases found in human heart is
      regulated by cGMP. In the case of PDE2, this regulation primarily involves the
      allosteric stimulation of cAMP hydrolysis by cGMP. For PDE3, cGMP acts as a
      competitive inhibitor of cAMP hydrolysis. Several cGMP-mediated responses in
      cardiac cells, including a potentiation of Ca(2+) currents and a diminution of
      the responsiveness to beta-adrenergic receptor agonists, have been shown to
      result from the effects of cGMP on cAMP hydrolysis. These effects appear to be
      dependent on the specific spatial distribution of the cGMP-generating and cAMP
      hydrolyzing proteins, as well as on the intracellular concentrations of the two
      cyclic nucleotides. Gaining a more precise understanding of how these cross-talk
      mechanisms are individually regulated and coordinated is an important direction
      for future research.

PMID- 17556672
TI  - Steroid and oxygen effects on eIF4F complex, mTOR, and ENaC translation in fetal
      lung epithelia.
AB  - Fetal distal lung epithelium (FDLE) must increase amiloride-sensitive epithelial
      Na(+) channel (ENaC) activity during the perinatal period to increase Na(+)
      transport and fluid clearance. Glucocorticosteroid (GC) levels increase, there is
      a 7-fold increase in Po(2) at birth, and we have previously shown that
      dexamethasone (DEX)-induced alpha-ENaC mRNA is efficiently translated only under
      postnatal (21%) O(2) (Otulakowski et al., AJRCMB 2006;34:204-212). Translation of
      mRNAs with long GC-rich 5'UTRs, such as alpha-ENaC mRNA, are sensitive to the
      amount of eIF4F, the mRNA 5'-cap binding complex composed of eIF4E and eIF4G. We
      now show, by Western blotting and m(7)GTP-Sepharose pull-down experiments, that
      in FDLE cultured under 3% O(2), DEX decreases formation of eIF4F and increases
      association of eIF4E with its inhibitor 4E-BP by changing 4E-BP phosphorylation.
      Conversely, FDLE cultured at 21% O(2) expressed lower levels of 4E-BP and
      maintained eIF4E-eIF4G association independent of DEX. Phosphorylation of 4E-BP
      is regulated by the kinase mTOR. Under 3% O(2), DEX decreased abundance of
      phosphorylated forms of the mTOR effectors, S6 kinase and ribosomal protein S6.
      Neither effect was associated with changes in REDD1, an upstream regulator of
      mTOR. When mTOR was inhibited (3 nM rapamycin) there was reduced 4E-BP
      phosphorylation, fewer ribosomes on alpha-ENaC mRNA, and decreased amiloride
      sensitive short-circuit current, but no change in ribosomal loading onto any of
      beta- or gamma-ENaC or cytokeratin 18 mRNAs. We speculate that at birth increased
      Po(2) acts with GC through an mTOR-related pathway to increase alpha-ENaC protein
      synthesis, thereby promoting lung fluid absorption.

PMID- 17556673
TI  - Fluvastatin inhibits hypoxic proliferation and p38 MAPK activity in pulmonary
      artery fibroblasts.
AB  - The earliest structural change in hypoxia-induced pulmonary hypertension is
      increased proliferation of adventitial fibroblasts. This fibroproliferative
      response occurs in acute and chronic hypoxic models, is dependent on p38 mitogen
      activated protein (MAP) kinase activation, is selective for the pulmonary
      circulation, and would seem an important therapeutic target. Simvastatin
      attenuates pulmonary vascular remodeling in animal models, but additional
      information regarding mechanisms of action, differential antiproliferative
      effects and dose responses of available statins is required for appropriate
      clinical trial design. Our objectives were to determine the effects of statins on
      acute hypoxia-induced proliferation and p38 MAP kinase activation in pulmonary
      and systemic artery fibroblasts, to assess the effects of cholesterol
      intermediates, prenyltransferase and related inhibitors, and to determine the
      statin's mechanism of action. Atorvastatin, fluvastatin, and simvastatin
      inhibited adventitial fibroblast proliferation. At low doses (1 microM), this
      effect was selective for hypoxic (versus serum-induced) proliferation and was
      also selective for pulmonary (versus systemic) fibroblasts. Complete inhibition
      of hypoxia-induced p38 MAP kinase activity was achieved at this 1-microM dose.
      The lipophilic statins exhibited similar potency. The statin effect was reversed
      by geranylgeranyl pyrophosphate and mimicked by geranylgeranyl transferase and
      Rac1 inhibitors. Hypoxia-induced p38 MAP kinase activation and proliferation in
      pulmonary adventitial fibroblasts is dependent on a geranylgeranylated signaling
      protein, probably Rac1. One micromolar of fluvastatin exhibits a circulation- and
      stimulus-selective antiproliferative effect on pulmonary artery fibroblasts. The
      pharmacokinetics of fluvastatin would suggest that its antiproliferative effects
      may be useful in pulmonary hypertension associated with hypoxia.

PMID- 17556675
TI  - Framing inequity safely: Whites' motivated perceptions of racial privilege.
AB  - Racial inequity was theorized to threaten Whites' self-image when inequity is
      framed as White privilege but not when framed as anti-Black discrimination.
      Manipulations of Whites' need for self-regard were hypothesized to affect their
      perceptions of White privilege but not of anti-Black discrimination. In
      Experiment 1, White participants reported less privilege when given threatening
      (vs. affirming) feedback on an intelligence or personality test; in contrast,
      perceptions of anti-Black discrimination were unaffected by self-concept
      manipulations. In Experiment 2, threatening (vs. affirming) feedback decreased
      privilege perceptions only among Whites high in racial identity. Using a value
      based self-affirmation manipulation, Experiment 3 replicated the effect of self
      image concerns on Whites' perceptions of privilege and provided evidence that
      self-concerns, through their effect on perceived privilege, influence Whites'
      support for redistributive social policies.

PMID- 17556674
TI  - Activity and inhibition resistance of a phospholipase-resistant synthetic
      surfactant in rat lungs.
AB  - This study investigates the activity and inhibition resistance in excised rat
      lungs of a novel synthetic surfactant containing the phospholipase-resistant
      diether phosphonolipid DEPN-8 plus 1.5% bovine surfactant protein (SP)-B/C
      compared to calf lung surfactant extract (CLSE). DEPN-8 + 1.5% SP-B/C surpassed
      CLSE in normalizing surfactant-deficient pressure-volume (P-V) deflation
      mechanics in lavaged excised lungs in the presence of phospholipase A(2) (PLA(2))
      or C18:1 lyso-phosphatidylcholine (LPC). DEPN-8 + 1.5% SP-B/C had activity equal
      to CLSE in normalizing P-V mechanics in the absence of inhibitors or in the
      presence of serum albumin. These physiologic activity findings were directly
      consistent with surface activity measurements on the pulsating bubble
      surfactometer. In the absence of inhibitors, DEPN-8 + 1.5% SP-B/C and CLSE
      rapidly reached minimum surface tensions < 1 mN/m (0.5 and 2.5 mg surfactant
      phospholipid/ml). DEPN-8 + 1.5% SP-B/C maintained its high surface activity in
      the presence of PLA(2), while the surface activity of CLSE was significantly
      inhibited by exposure to this enzyme. DEPN-8 + 1.5% SP-B/C also had greater
      surface activity than CLSE in the presence of LPC, and the two surfactants had
      equivalent surface activity in the presence of albumin. DEPN-8 + 1.5% SP-B/C also
      had slightly greater surface activity than CLSE when exposed to peroxynitrite in
      pulsating bubble studies. These results support the potential of developing
      highly active and inhibition-resistant synthetic exogenous surfactants containing
      DEPN-8 + apoprotein/peptide constituents for use in treating direct pulmonary
      forms of clinical acute lung injury (ALI) and the acute respiratory distress
      syndrome (ARDS).

PMID- 17556677
TI  - Dietary prevention of atherosclerosis: go with whole grains.

PMID- 17556678
TI  - Homocysteine--an indicator of a healthy diet?

PMID- 17556679
TI  - A collaborative effort to apply the evidence-based review process to the field of
      nutrition: challenges, benefits, and lessons learned.
AB  - Evidence-based systematic reviews evaluating dietary intake and nutritional
      interventions are becoming common but are relatively few compared with other
      applications. Concerns remain that systematic reviews of nutrition topics pose
      several unique challenges. We present a successful collaboration to
      systematically review the health effects of a common nutrient, n-3 (or omega-3)
      fatty acids, across a wide range of clinical conditions. More generally, we
      discuss the challenges faced and the lessons learned during the review, the
      benefits of systematic review of nutritional topics, and recommendations for
      conducting and reviewing nutrition-related studies. Through a structured but
      flexible process, 3 Evidence-based Practice Centers in the Agency for Healthcare
      Research and Quality program produced 11 reports on a wide range of n-3 fatty
      acid-related topics. An important resource has been created, through which
      nutrition and dietetics researchers, clinical dietitians and nutritionists,
      clinicians, and the general public can understand the state of the science. The
      process identified challenges and problems in evaluating the health effects of n
      3 fatty acid consumption, highlighted challenges to reviewing the human nutrition
      literature, and yielded recommendations for future research. The goals of these
      systematic reviews, the processes that were used, the benefits and limitations of
      the collaboration, and the conclusions of the reviews, including recommendations
      for future research, are summarized here.

PMID- 17556680
TI  - Docosahexaenoic and arachidonic acid concentrations in human breast milk
      worldwide.
AB  - Concentrations of the long-chain polyunsaturated fatty acids (LCPUFAs)
      docosahexaenoic acid (DHA, 22:6n-3) and arachidonic acid (AA, 20:4n-6) in human
      breast milk are important indicators of infant formula DHA and AA concentrations,
      and recent evidence suggests that neural maturation of breastfed infants is
      linked to breast-milk LCPUFA concentrations. We report a descriptive meta
      analysis that considered 106 studies of human breast milk culled to include only
      studies that used modern analysis methods capable of making accurate estimates of
      fatty acid (FA) profiles and criteria related to the completeness of reporting.
      The final analysis included 65 studies of 2474 women. The mean (+/-SD)
      concentration of DHA in breast milk (by wt) is 0.32 +/- 0.22% (range: 0.06-1.4%)
      and that of AA is 0.47 +/- 0.13% (range: 0.24-1.0%), which indicates that the DHA
      concentration in breast milk is lower than and more variable than that of AA. The
      highest DHA concentrations were primarily in coastal populations and were
      associated with marine food consumption. The correlation between breast-milk DHA
      and AA concentrations was significant but low (r = 0.25, P = 0.02), which
      indicates that the mean ratio of DHA to AA in regional breast milk varies widely.
      This comprehensive analysis of breast-milk DHA and AA indicates a broad range of
      these nutrients worldwide and serves as a guide for infant feeding.

PMID- 17556681
TI  - Dietary energy density in the treatment of obesity: a year-long trial comparing 2
      weight-loss diets.
AB  - BACKGROUND: Consuming foods low in energy density (kcal/g) decreases energy
      intake over several days, but the effectiveness of this strategy for weight loss
      has not been tested. OBJECTIVE: The effects on weight loss of 2 strategies for
      reducing the energy density of the diet were compared over 1 y. DESIGN: Obese
      women (n = 97) were randomly assigned to groups counseled either to reduce their
      fat intake (RF group) or to reduce their fat intake and increase their intake of
      water-rich foods, particularly fruit and vegetables (RF+FV group). No goals for
      energy or fat intake were assigned; the subjects were instructed to eat ad
      libitum amounts of food while following the principles of their diet. RESULTS:
      After 1 y, study completers (n = 71) in both groups had significant decreases in
      body weight (P < 0.0001). Subjects in the RF+FV group, however, had a
      significantly different pattern of weight loss (P = 0.002) than did subjects in
      the RF group. After 1 y, the RF+FV group lost 7.9 +/- 0.9 kg and the RF group
      lost 6.4 +/- 0.9 kg. Analysis of all randomly assigned subjects also showed a
      different pattern of weight loss between groups (P = 0.021). Diet records
      indicated that both groups had similar reductions in fat intake. The RF+FV group,
      however, had a lower dietary energy density than did the RF group (P = 0.019) as
      the result of consuming a greater weight of food (P = 0.025), especially fruit
      and vegetables (P = 0.037). The RF+FV group also reported less hunger (P =
      0.003). CONCLUSION: Reducing dietary energy density, particularly by combining
      increased fruit and vegetable intakes with decreased fat intake, is an effective
      strategy for managing body weight while controlling hunger.

PMID- 17556682
TI  - Metabolic and behavioral predictors of weight gain in Hispanic children: the Viva
      la Familia Study.
AB  - BACKGROUND: Despite the high prevalence of overweight among Hispanic children in
      the United States, definitive predictors of weight gain have not been identified
      in this population. OBJECTIVE: The study objective was to test sociodemographic,
      metabolic, and behavioral predictors of 1-y weight gains in a large cohort of
      Hispanic children studied longitudinally. DESIGN: Subjects (n = 879) were
      siblings from 319 Hispanic families enrolled in the Viva la Familia Study.
      Families were required to have at least one overweight child aged 4-19 y. One
      year changes in weight and body composition by dual-energy X-ray absorptiometry
      were measured. Data were from parental interviews, birth certificates, multiple
      pass 24-h dietary recalls, 3-d accelerometry, 24-h respiration calorimetry,
      measurements of eating in the absence of hunger, and measurement of fasting blood
      biochemistry indexes by radioimmunoassay. Generalized estimating equations and
      principal component analysis were applied. RESULTS: Weight gain increased with
      age (P = 0.001), peaking at approximately 10 y of age in girls and approximately
      11 y of age in boys. Mean (+/-SD) weight gain was significantly higher in
      overweight (7.5 +/- 3.7 kg/y) than in nonoverweight (4.4 +/- 2.4 kg/y) children
      and in boys than in girls. When adjusted for age, age squared, sex, and Tanner
      stage, the final model indicated a child's body mass index (BMI; kg/m2) status,
      maternal BMI, energy expenditure (total energy expenditure, basal metabolic rate,
      and sleeping metabolic rate), and fasting blood biochemistry indexes (total
      triiodothyronine, insulin, leptin, and ghrelin) as independent, positive
      predictors of weight gain (P = 0.01-0.001). CONCLUSION: Knowledge of the
      metabolic and behavioral predictors of weight gain in Hispanic children will
      inform prevention and treatment efforts to address this serious public health
      problem in the United States.

PMID- 17556683
TI  - The solid fat content of stearic acid-rich fats determines their postprandial
      effects.
AB  - BACKGROUND: The process of randomization is used commercially to harden fats as
      an alternative to partial hydrogenation, but its effects on cardiovascular
      disease risk factors are uncertain. OBJECTIVE: The objective was to compare the
      chronic and acute effects of randomization of a fat rich in 1,3-distearyl, 2
      oleyl glycerol on fasting and postprandial lipids, glucose, insulin, and
      activated clotting factor VII (FVIIa) concentrations. DESIGN: A crossover design
      study in 16 men compared fasting and postprandial lipid, glucose, insulin, and
      FVIIa concentrations at baseline and after a 3-wk diet providing 30 g
      unrandomized or randomized shea butter and sunflower oil blends (SSOBs), both of
      which contained approximately 50% stearic acid. Fecal fat excretion was measured
      during each dietary period. Postprandial changes were assessed after the
      consumption of meals providing 50 g test fat. A subsequent study compared
      postprandial changes after the consumption of an oleic acid-rich sunflower oil
      meal and an unrandomized SSOB meal. RESULTS: Both SSOBs were well digested and
      absorbed. Randomization did not affect fasting or postprandial lipid, glucose,
      insulin, or FVIIa concentrations. Compared with the oleic acid-rich meal, the
      unrandomized SSOB resulted in 53% lower postprandial lipemia, 23% higher hepatic
      lipase activity, and a 25% lower postprandial increase in FVIIa concentration.
      The solid fat contents at 37 degrees C were 22%, 41%, and 0% with the
      unrandomized SSOB, randomized SSOB, and oleic acid-rich meals, respectively.
      CONCLUSIONS: Stearic acid-rich triacylglycerol in both unrandomized and
      randomized forms does not adversely affect lipid risk factors for cardiovascular
      disease. The high proportion of solid fat at 37 degrees C may explain the
      decreased postprandial lipemic response.

PMID- 17556684
TI  - Whole-grain intake and carotid artery atherosclerosis in a multiethnic cohort:
      the Insulin Resistance Atherosclerosis Study.
AB  - BACKGROUND: Whole-grain intake has been shown to be inversely associated with
      cardiovascular events, but an association with atherosclerosis is less well
      established. OBJECTIVE: We sought to evaluate the association of whole-grain
      intake with carotid intimal medial thickness (IMT) and IMT progression in a
      multiethnic cohort. DESIGN: This study evaluated 1178 participants in the Insulin
      Resistance Atherosclerosis Study. Baseline whole-grain intake was estimated on
      the basis of intake of dark breads, cooked cereals, and high-fiber cereals
      assessed with a validated food-frequency questionnaire. Bilateral carotid IMT was
      evaluated ultrasonographically, yielding 16 IMT measures at baseline and year 5.
      Multivariate models evaluated the independent association of whole-grain intake
      with common carotid artery (CCA) and internal carotid artery (ICA) IMT and IMT
      progression. RESULTS: The cohort had a mean (+/-SD) age of 55.2 +/- 8.4 y and was
      56% female. The baseline median whole-grain intake was 0.79 servings/d. Whole
      grain intake was inversely associated with CCA IMT (beta +/- SE: -0.043 +/-
      0.013, P = 0.005) and IMT progression (beta +/- SE: -0.019 +/- 0.011, P = 0.09)
      in models adjusted for demographics, energy intake, energy expenditure,
      cardiovascular disease risk factors, and medication use. This association was
      less significant for ICA IMT (beta +/- SE: -0.049 +/- 0.023, P = 0.05) and not
      significant for ICA IMT progression (beta +/- SE: -0.013 +/- 0.014, P = 0.35).
      The relation between whole-grain intake and CCA IMT remained significant after
      adjustment for mediating pathways (lipids, adiposity, and insulin resistance),
      nutrient constituents, and a principal components-derived healthy dietary
      pattern. CONCLUSIONS: Whole-grain intake is inversely associated with CCA IMT,
      and this relation is not attributable to individual risk intermediates, single
      nutrient constituents, or larger dietary patterns.

PMID- 17556685
TI  - Snack chips fried in corn oil alleviate cardiovascular disease risk factors when
      substituted for low-fat or high-fat snacks.
AB  - BACKGROUND: The perception that all high-fat snacks are unhealthy may be wrong.
      OBJECTIVE: We aimed to assess whether replacing low-fat and high-fat snacks with
      snacks rich in polyunsaturated fatty acids (PUFAs) and low in saturated and trans
      fatty acids would improve cardiovascular health. DESIGN: Thirty-three adults
      participated in a randomized crossover trial of 3 controlled feeding phases of 25
      d each in which a different type of snack was provided: low-fat (30.8% of energy
      from fat, 5.2% of energy from PUFAs), high-PUFA (36.3% of energy from fat, 9.7%
      of energy from PUFAs), or high-fat (37.9% of energy from fat, 5.8% of energy from
      PUFAs) snack. RESULTS: Each diet reduced LDL- and total cholesterol
      concentrations, but reductions were greater with the low-fat and the high-PUFA
      diets than with the high-fat diet: LDL cholesterol (11.8% and 12.5% compared with
      8.8%, respectively; P = 0.03 and 0.01), total cholesterol (10.5% and 10.7%
      compared with 7.9%, respectively; P = 0.03 and 0.02). The high-PUFA diet tended
      to reduce triacylglycerol concentrations (9.4%; P = 0.06), and this change was
      greater than that with the low-fat (P = 0.028) and high-fat (P = 0.0008) diets.
      CONCLUSIONS: These data show that snack type affects cardiovascular health.
      Consuming snack chips rich in PUFA and low in saturated or trans fatty acids
      instead of high-saturated fatty acid and trans fatty acid or low-fat snacks leads
      to improvements in lipid profiles concordant with reductions in cardiovascular
      disease risk.

PMID- 17556686
TI  - Mechanisms for the acute effect of fructose on postprandial lipemia.
AB  - BACKGROUND: A high fructose intake can lead to postprandial
      hypertriacylglycerolemia. The underlying mechanism is unclear. OBJECTIVE: The
      objective of the study was to investigate the mechanisms involved in fructose
      induced hypertriacylglycerolemia and the contribution of de novo lipogenesis in
      an acute setting. DESIGN: In a randomized, crossover study, 14 subjects were
      given a fructose or glucose test meal after an overnight fast. [(2)H2]Palmitate
      and [U(13)C]d-fructose or [U(13)C]d-glucose were added to trace the handling of
      dietary fats and the fate of dietary sugars in the body. Blood samples were taken
      before and after the meal. Respiratory exchange ratio was measured by using
      indirect calorimetry, and breath samples were collected. RESULTS: Plasma
      triacylglycerol and VLDL-triacylglycerol concentrations were significantly higher
      (P = 0.001 for both), whereas the concentrations of insulin and [(2)H2]palmitate
      in nonesterified fatty acids were significantly lower after fructose than after
      glucose (P = 0.002 and 0.03, respectively). The respiratory exchange ratio was
      higher after fructose (P = 0.04); significantly (P = 0.003) more carbon from
      sugars was recovered in breath carbon dioxide over 6 h after fructose (30.5%)
      than after glucose (24.5%). At 240 min, newly synthesized fatty acids from
      fructose made up approximately 0.4% of circulating VLDL-triacylglycerol, whereas
      newly synthesized triacylglycerol-glycerol made up 38%. Newly synthesized fatty
      acids and triacylglycerol-glycerol from glucose contributed almost none of VLDL
      triacylglycerol (P = 0.002 and 0.007 for glucose and fructose, respectively).
      CONCLUSIONS: The lower insulin excursion after fructose may result in less
      activation of adipose tissue lipoprotein lipase, which led to impaired
      triacylglycerol clearance. The contribution of de novo lipogenesis to fructose
      induced hypertriacylglycerolemia is small, but its effect on altering the
      partitioning of fatty acids toward esterification may be considerable.

PMID- 17556687
TI  - Dietary glycemic index, dietary glycemic load, and cardiovascular disease in
      middle-aged and older Swedish men.
AB  - BACKGROUND: In women, dietary glycemic index (GI) and dietary glycemic load (GL)
      have been associated with cardiovascular disease; in men, however, the evidence
      for an association is weaker. OBJECTIVE: We tested the hypothesis that men
      consuming diets high in GI or GL have a greater risk of cardiovascular disease.
      DESIGN: At baseline, we assessed dietary GI and dietary GL by using food
      frequency questionnaires in 36 246 Swedish men aged 45-79 y without diabetes or
      prior cardiovascular disease. Participants were followed through inpatient, cause
      of-death, and death registries from 1 January 1998 until 31 December 2003 for
      myocardial infarction, ischemic stroke, hemorrhagic stroke, and cardiovascular
      mortality and until 31 December 2005 for all-cause mortality. We used Cox models
      with age as the time scale to estimate relative risks adjusted for cigarette
      smoking, body mass index, physical activity, demographic characteristics, and
      nutritional factors. RESULTS: Dietary GI and dietary GL were not associated with
      myocardial infarction (n = 1324), ischemic stroke (n = 692), cardiovascular
      mortality (n = 785), or all-cause mortality (n = 2959). Dietary GL was associated
      with hemorrhagic stroke [n = 165; relative risk = 1.44 comparing extreme
      quartiles (95% CI: 0.91, 2.27); P for trend = 0.047]. CONCLUSIONS: Dietary GI and
      dietary GL were not associated with ischemic cardiovascular disease or mortality,
      but dietary GL was associated with a greater risk of hemorrhagic stroke.
      Discrepancies between these findings and those of previous studies may be due to
      variations in the associations by sex or to differences in dietary contributions
      to GI and GL.

PMID- 17556688
TI  - Increased plasma concentrations of lipoprotein(a) during a low-fat, high
      carbohydrate diet are associated with increased plasma concentrations of
      apolipoprotein C-III bound to apolipoprotein B-containing lipoproteins.
AB  - BACKGROUND: Low-fat, high-carbohydrate (LFHC) diets have been shown to increase
      plasma concentrations of lipoprotein(a) [Lp(a)] and of triacylglycerol- rich
      lipoproteins (TRLs). OBJECTIVE: We tested whether increases in plasma Lp(a)
      induced by an LFHC diet are related to changes in TRLs. DESIGN: Healthy men
      (study 1; n = 140) consumed for 4 wk each a high-fat, low-carbohydrate diet
      (HFLC; 40% fat, 45% carbohydrate) and an LFHC diet (20% fat, 65% carbohydrate).
      Plasma lipids; lipoproteins; apolipoprotein (apo) B, A-I, and C-III; and Lp(a)
      were measured at the end of each diet. In a second group of men following a
      similar dietary protocol (study 2; n = 33), we isolated apo(a)-containing
      particles by immunoaffinity chromatography and determined the concentrations of
      apo C-III in ultracentrifugally isolated subfractions of apo B-containing
      lipoproteins. RESULTS: In study 1, plasma concentrations of Lp(a) (P < 0.001),
      triacylglycerol (P < 0.001), apo B (P < 0.005), apo C-III (P < 0.005), and apo C
      III in apo B-containing lipoproteins (non-HDL apo C-III) (P < 0.001) were
      significantly higher with the LFHC diet than with the HFLC diet. Stepwise
      multiple linear regression analysis showed that the association of changes in
      Lp(a) with changes in non-HDL apo C-III was independent of changes in body mass
      index, apo B, LDL cholesterol, and HDL cholesterol. Plasma lipid and lipoprotein
      changes were similar in study 2, and we found that both total apo C-III and the
      apo C-III content of apo(a)-containing particles were increased in a TRL fraction
      consisting predominantly of large VLDL particles [TRL-apo(a)]. CONCLUSIONS: The
      increase in plasma Lp(a) with an LFHC diet is significantly associated with an
      increase in non-HDL apo C-III. Enrichment of TRL-apo(a) with apo C-III may
      contribute to this dietary effect on Lp(a) concentrations.

PMID- 17556689
TI  - Adolescent skinfold thickness is a better predictor of high body fatness in
      adults than is body mass index: the Amsterdam Growth and Health Longitudinal
      Study.
AB  - BACKGROUND: Body mass index (BMI) during adolescence is predictive of BMI at
      adult age. However, BMI cannot distinguish between lean and fat body mass.
      Skinfold thickness may be a better predictor of body fatness. OBJECTIVE: The
      objective of this study was to evaluate the relations between BMI and skinfold
      thickness during adolescence and body fatness during adulthood. DESIGN: We
      included 168 men and 182 women from the Amsterdam Growth and Health Longitudinal
      Study, a prospective study that conducted 8 measurements of BMI and skinfold
      thickness between 1976 and 2000. BMI and skinfold thickness during adolescence
      were analyzed in relation to adult body fatness measured at a mean age of 37 y
      with dual-energy X-ray absorptiometry. RESULTS: None of the boys and 1.7% of the
      girls were overweight at baseline, whereas the prevalence of high body fatness
      during adulthood was 29% in men and 32% in women. At the ages of 12-16 y,
      skinfold thickness was more strongly associated with adult body fatness than was
      BMI. Age-specific relative risks for a high level of adult body fatness varied
      between 2.3 and 4.0 in boys and between 2.1 and 4.3 in girls in the highest
      versus the lowest tertile of the sum of 4 skinfold thicknesses. For the highest
      tertile of BMI, the relative risk varied between 0.8 and 2.1 in boys and between
      1.3 and 1.8 in girls. CONCLUSION: Skinfold thickness during adolescence is a
      better predictor of high body fatness during adulthood than is BMI during
      adolescence.

PMID- 17556690
TI  - Body mass index and hip and thigh circumferences are negatively associated with
      visceral adipose tissue after control for waist circumference.
AB  - BACKGROUND: Waist circumference (WC) is positively associated with morbidity and
      mortality with or without control for hip circumference (HC) or body mass index
      (BMI; in kg/m(2)). This association is thought to be explained by an expanded
      visceral adipose tissue (VAT) depot. Conversely, HC and BMI are negatively
      associated with morbidity and mortality after control for WC. Whether this
      inverse association is explained in part by the ability of HC and BMI to identify
      subjects with increased subcutaneous adipose tissue (SAT), increased skeletal
      muscle (SM) mass, or decreased VAT after control for WC is unclear. OBJECTIVE: We
      examined the independent associations between WC, HC, thigh circumference (ThC),
      and BMI with VAT and total, lower-body, and abdominal SAT and SM. DESIGN: Total
      and regional body composition were measured in 256 white men and women with
      magnetic resonance imaging. RESULTS: WC, HC, ThC, and BMI were all positively
      correlated with total, lower-body, and abdominal SAT and SM and with VAT. After
      statistical control for WC, HC, ThC, and BMI remained positively associated with
      total, lower-body, and abdominal SAT and SM (men only) but were negatively
      associated with VAT (P < 0.05). HC (P < 0.05) but not BMI (P > 0.10) or ThC (P =
      0.06) remained negatively associated with VAT after further control for age.
      CONCLUSIONS: HC, ThC, and BMI are positively associated with total, lower-body,
      and abdominal SAT and SM but negatively associated with VAT after control for WC.
      However, only HC remained negatively associated with VAT after control for age
      and WC.

PMID- 17556691
TI  - Effect of alcoholic beverages on postprandial glycemia and insulinemia in lean,
      young, healthy adults.
AB  - BACKGROUND: Ethanol's ability to inhibit gluconeogenesis might reduce
      postprandial glycemia in realistic meal settings. OBJECTIVE: The objective was to
      explore the effect of 3 types of alcoholic beverages consumed alone, with a meal,
      or 1 h before a meal on postprandial glycemia in healthy subjects. DESIGN: In
      study 1, isoenergetic (1000 kJ) servings of beer, white wine, and gin were
      compared with a 1000-kJ portion of white bread. In study 2, the same servings
      were compared with water as an accompaniment to a bread meal. In study 3, 20-g
      alcohol portions were served as a premeal drink. Fingertip capillary blood
      samples were taken at regular intervals over 2-3 h. RESULTS: In study 1, the mean
      (+/-SE) glucose scores for beer (58 +/- 11), wine (7 +/- 3), and gin (10 +/- 5)
      were significantly lower (P < 0.001) than those for bread (= 100). In study 2,
      meals consumed with beer (84 +/- 11; P = 0.03), wine (63 +/- 6; P < 0.001), and
      gin (80 +/- 12; P = 0.007) produced less glycemia than did the meal consumed with
      water (= 100). In study 3, all 3 beverages reduced the postprandial glycemic
      response to the subsequent meal (67 +/- 5, 75 +/- 6, and 78 +/- 4 with the beer,
      wine, and gin trials, respectively; P < 0.003). CONCLUSION: In realistic
      settings, alcoholic beverage consumption lowers postprandial glycemia by 16-37%,
      which represents an unrecognized mechanism by which alcohol may reduce the risk
      of chronic disease.

PMID- 17556692
TI  - Effect of cinnamon on postprandial blood glucose, gastric emptying, and satiety
      in healthy subjects.
AB  - BACKGROUND: Previous studies of patients with type 2 diabetes showed that
      cinnamon lowers fasting serum glucose, triacylglycerol, and LDL- and total
      cholesterol concentrations. OBJECTIVE: We aimed to study the effect of cinnamon
      on the rate of gastric emptying, the postprandial blood glucose response, and
      satiety in healthy subjects. DESIGN: The gastric emptying rate (GER) was measured
      by using standardized real-time ultrasonography. Fourteen healthy subjects were
      assessed by using a crossover trial. The subjects were examined after an 8-h fast
      if they had normal fasting blood glucose concentrations. GER was calculated as
      the percentage change in the antral cross-sectional area 15-90 min after
      ingestion of 300 g rice pudding (GER1) or 300 g rice pudding and 6 g cinnamon
      (GER2). RESULTS: The median value of GER1 was 37%, and that of GER2 was 34.5%.
      The addition of cinnamon to the rice pudding significantly delayed gastric
      emptying and lowered the postprandial glucose response (P < 0.05 for both). The
      reduction in the postprandial blood glucose concentration was much more
      noticeable and pronounced than was the lowering of the GER. The effect of
      cinnamon on satiety was not significant. CONCLUSIONS: The intake of 6 g cinnamon
      with rice pudding reduces postprandial blood glucose and delays gastric emptying
      without affecting satiety. Inclusion of cinnamon in the diet lowers the
      postprandial glucose response, a change that is at least partially explained by a
      delayed GER.

PMID- 17556693
TI  - Quantification of the bioavailability of riboflavin from foods by use of stable
      isotope labels and kinetic modeling.
AB  - BACKGROUND: Discrepancies have been reported between estimates of the prevalence
      of riboflavin deficiency based on intakes of riboflavin and estimates based on
      measures of riboflavin status. One reason for this may be an overestimate of the
      bioavailability of riboflavin from foods, about which relatively little is known.
      OBJECTIVE: We aimed to quantify the bioavailability of riboflavin from milk and
      spinach by using stable-isotope labels and a urinary monitoring technique and by
      a plasma appearance method based on kinetic modeling. DESIGN: Twenty healthy
      women aged 18-65 y were recruited for a randomized crossover study performed with
      extrinsically labeled (13C) milk and intrinsically labeled (15N) spinach as
      sources of riboflavin. An intravenous bolus of labeled riboflavin was
      administered with each test meal to assess the apparent volume of distribution of
      riboflavin in plasma. RESULTS: No significant differences were noted in
      riboflavin absorption from the spinach meal and from the milk meal according to
      either the urinary monitoring technique (60 +/- 8.0% and 67 +/- 5.4%,
      respectively; P = 0.549) or the plasma appearance method (20 +/- 2.8% and 23 +/-
      5.3%, respectively; P = 0.670). CONCLUSIONS: A large fraction of newly absorbed
      riboflavin is removed by the liver on "first pass." The plasma appearance method
      therefore underestimates riboflavin bioavailability and should not be used to
      estimate riboflavin bioavailability from foodstuffs. Urinary monitoring suggests
      that riboflavin from spinach is as bioavailable as is riboflavin from milk.

PMID- 17556694
TI  - Efficacy of daily and monthly high-dose calciferol in vitamin D-deficient
      nulliparous and lactating women.
AB  - BACKGROUND: We previously found a high prevalence of vitamin D deficiency and low
      medication regimen compliance in Arab and East Indian women residing in the
      United Arab Emirates (UAE). The appropriate dosing regimen for improving vitamin
      D status in this population is not known. OBJECTIVE: We aimed to determine the
      efficacy of daily and monthly supplementation with vitamin D2, the only high-dose
      calciferol available in the UAE, in lactating and nulliparous women. DESIGN:
      Healthy lactating (n = 90) and nulliparous (n = 88) women were randomly assigned
      to consume 2000 IU vitamin D2/d or 60,000 IU vitamin D2/mo for 3 mo. Serum 25
      hydroxyvitamin D [25(OH)D] concentrations were measured by radioimmunoassay at
      baseline and every month. RESULTS: Most women had vitamin D deficiency [ie,
      25(OH)D < 50 nmol/L] at study entry. Mean +/- SD 25(OH)D concentrations at 3 mo
      were significantly higher than baseline in both lactating (39.8 +/- 12.4 and 25.2
      +/- 10.7 nmol/L, respectively) and nulliparous (40.4 +/- 23.4 and 19.3 +/- 12.2
      nmol/L, respectively) women (P < 0.001 for both). In total, vitamin D
      supplementation was effective in achieving serum 25(OH)D concentrations of >or=50
      nmol/L in 21 (30%) of 71 women at endpoint. CONCLUSIONS: Oral vitamin D2
      supplementation with 2000 IU/d or 60,000 IU/mo for 3 mo was safe, and it
      increased serum 25(OH)D concentrations significantly; however, only a small
      proportion of the women studied achieved concentrations of >or=50 nmol/L. This
      suggests that, when sunlight exposure is limited, doses of vitamin D2 higher than
      those currently studied may be needed. Monthly dosing appears to be a safe and
      effective alternative to daily dosing.

PMID- 17556695
TI  - Maternal consumption of a docosahexaenoic acid-containing functional food during
      pregnancy: benefit for infant performance on problem-solving but not on
      recognition memory tasks at age 9 mo.
AB  - BACKGROUND: There are few studies reporting on docosahexaenoic acid (DHA, 22:6n
      3) supplementation during pregnancy and infant cognitive function. DHA
      supplementation in pregnancy and infant problem solving in the first year have
      not been investigated. OBJECTIVE: We tested the hypothesis that infants born to
      women who consumed a DHA-containing functional food during pregnancy would
      demonstrate better problem-solving abilities and recognition memory than would
      infants born to women who consumed the placebo during pregnancy. DESIGN: In a
      double-blind, placebo-controlled, randomized trial, pregnant women consumed a DHA
      containing functional food or a placebo from gestation week 24 until delivery.
      Study groups received DHA-containing cereal-based bars (300 mg DHA/92-kcal bar;
      average consumption: 5 bars/wk; n = 14) or cereal-based placebo bars (n = 15).
      The Infant Planning Test and Fagan Test of Infant Intelligence were administered
      to infants at age 9 mo. The problem-solving trial included a support step and a
      search step. The procedure was scored on the basis of the infant's performance on
      each step and on the entire problem (intention score and total intentional
      solutions). Scores were generated on the basis of the cumulative performance of
      the infant on 5 trials. RESULTS: Treatment had significant effects on the
      performance of problem-solving tasks: total intention score (P = 0.017), total
      intentional solutions (P = 0.011), and number of intentional solutions on both
      cloth (P = 0.008) and cover (P = 0.004) steps. There were no significant
      differences between groups in any measure of Fagan Test of Infant Intelligence.
      CONCLUSION: These data point to a benefit for problem solving but not for
      recognition memory at age 9 mo in infants of mothers who consumed a DHA
      containing functional food during pregnancy.

PMID- 17556696
TI  - Infant feeding method and obesity: body mass index and dual-energy X-ray
      absorptiometry measurements at 9-10 y of age from the Avon Longitudinal Study of
      Parents and Children (ALSPAC).
AB  - BACKGROUND: Previous studies reported inconsistent associations between
      breastfeeding and body mass index (BMI; in kg/m2). Associations with body fatness
      are unknown. OBJECTIVE: We investigated the association of breastfeeding with
      fatness measured by dual-energy X-ray absorptiometry. DESIGN: The prospective
      cohort study involved 4325 singletons with measurements at 9-10 y of age to
      assess the main outcomes of BMI and total and trunk fat masses. RESULTS:
      Prevalence of any breastfeeding was 82%. In crude analyses, breastfeeding was
      inversely associated with total fat mass [% change per category increase (4
      categories)] in breastfeeding duration (-4.4%; 95% CI: -3.1%, -5.6%) and trunk
      fat mass (-0.5%; 95% CI: -1.1%, 0.1%); the odds of adiposity were measured by
      total [odds ratio (OR): 0.81; 95% CI: 0.75, 0.88] and trunk (OR: 0.78; 95% CI:
      0.71, 0.84) fat masses in the top decile. In adjusted models, the inverse
      association of breastfeeding with mean total fat mass was attenuated by 59% (%
      change per category increase in breastfeeding duration: -1.8%; 95% CI: -0.5%, 
      3.1%), but associations with trunk fat mass (% change per category increase in
      breastfeeding duration: -0.6%; 95% CI: 0.0%, -1.3%) and the ORs for total (0.76;
      95% CI: 0.69, 0.84) and trunk (0.74; 95% CI: 0.67, 0.81) fat masses in the top
      decile were little altered. Children breastfed >or=6 mo had the lowest odds of
      total fat mass in the top decile (OR: 0.45; 95% CI: 0.33, 0.62). In multivariate
      models, there was little evidence that breastfeeding was associated with mean or
      threshold values of BMI. CONCLUSIONS: The protective association of breastfeeding
      with mean total fat mass was attenuated somewhat after adjustment for
      confounders, which indicated that confounding may explain this association.
      Breastfeeding may protect against obesity if maintained for >or=6 mo.

PMID- 17556697
TI  - Vitamin D and calcium supplementation reduces cancer risk: results of a
      randomized trial.
AB  - BACKGROUND: Numerous observational studies have found supplemental calcium and
      vitamin D to be associated with reduced risk of common cancers. However,
      interventional studies to test this effect are lacking. OBJECTIVE: The purpose of
      this analysis was to determine the efficacy of calcium alone and calcium plus
      vitamin D in reducing incident cancer risk of all types. DESIGN: This was a 4-y,
      population-based, double-blind, randomized placebo-controlled trial. The primary
      outcome was fracture incidence, and the principal secondary outcome was cancer
      incidence. The subjects were 1179 community-dwelling women randomly selected from
      the population of healthy postmenopausal women aged >55 y in a 9-county rural
      area of Nebraska centered at latitude 41.4 degrees N. Subjects were randomly
      assigned to receive 1400-1500 mg supplemental calcium/d alone (Ca-only),
      supplemental calcium plus 1100 IU vitamin D3/d (Ca + D), or placebo. RESULTS:
      When analyzed by intention to treat, cancer incidence was lower in the Ca + D
      women than in the placebo control subjects (P < 0.03). With the use of logistic
      regression, the unadjusted relative risks (RR) of incident cancer in the Ca + D
      and Ca-only groups were 0.402 (P = 0.01) and 0.532 (P = 0.06), respectively. When
      analysis was confined to cancers diagnosed after the first 12 mo, RR for the Ca +
      D group fell to 0.232 (CI: 0.09, 0.60; P < 0.005) but did not change
      significantly for the Ca-only group. In multiple logistic regression models, both
      treatment and serum 25-hydroxyvitamin D concentrations were significant,
      independent predictors of cancer risk. CONCLUSIONS: Improving calcium and vitamin
      D nutritional status substantially reduces all-cancer risk in postmenopausal
      women. This trial was registered at clinicaltrials.gov as NCT00352170.

PMID- 17556698
TI  - The D1822V APC polymorphism interacts with fat, calcium, and fiber intakes in
      modulating the risk of colorectal cancer in Portuguese persons.
AB  - BACKGROUND: Both genetic and environmental factors affect the risk of colorectal
      cancer (CRC). OBJECTIVE: We aimed to examine the interaction between the D1822V
      polymorphism of the APC gene and dietary intake in persons with CRC. DESIGN:
      Persons with CRC (n = 196) and 200 healthy volunteers, matched for age and sex in
      a case-control study, were evaluated with respect to nutritional status and
      lifestyle factors and for the D1822V polymorphism. RESULTS: No significant
      differences were observed in energy and macronutrient intakes. Cases had
      significantly (P < 0.05) lower intakes of carotenes, vitamins C and E, folate,
      and calcium than did controls. Fiber intake was significantly (P = 0.004) lower
      in cases than in controls, whereas alcohol consumption was associated with a 2
      fold risk of CRC. In addition, cases were significantly (P = 0.001) more likely
      than were controls to be sedentary. The homozygous variant for the APC gene (VV)
      was found in 4.6% of cases and in 3.5% of controls. Examination of the potential
      interactions between diet and genotype found that a high cholesterol intake was
      associated with a greater risk of colorectal cancer only in noncarriers (DD) of
      the D1822V APC allele (odds ratio: 1.66; 95% CI: 1.00, 2.76). In contrast, high
      fiber and calcium intakes were more markedly associated with a lower risk of CRC
      in patients carrying the polymorphic allele (DV/VV) (odds ratio: 0.50; 95% CI:
      0.27, 0.94 for fiber; odds ratio: 0.51; 95% CI: 0.28, 0.93 for calcium) than in
      those without that allele. CONCLUSION: These results suggest a significant
      interaction between the D1822V polymorphism and the dietary intakes of
      cholesterol, calcium, and fiber for CRC risk.

PMID- 17556699
TI  - Dietary fat and plasma total homocysteine concentrations in 2 adult age groups:
      the Hordaland Homocysteine Study.
AB  - BACKGROUND: The intake of n-3 (formerly called omega-3) fatty acids (FAs) may be
      inversely associated with plasma total homocysteine (tHcy) concentrations, but
      the epidemiologic data are sparse. OBJECTIVE: We examined the association between
      dietary fat and tHcy in a Norwegian population. DESIGN: A cross-sectional,
      population-based study of 5917 subjects in 2 age groups (47-49 and 71-74 y old)
      was conducted with the use of food-frequency questionnaires and measurement of
      plasma tHcy concentrations. RESULTS: The intake of saturated FAs (SFAs) was
      positively and significantly (P for trend < 0.001) associated with tHcy
      concentrations; the difference in plasma tHcy concentrations between the highest
      and lowest quartiles of SFAs was 8.8%. The intake of marine very-long-chain n-3
      FAs was inversely associated with tHcy concentrations; the difference in plasma
      tHcy concentrations between the lowest and the highest quartiles was -5.0% (P for
      trend < 0.001). Intakes of total and monounsaturated fat also were positively
      associated with plasma tHcy concentrations (P for trend < 0.001 and < 0.005,
      respectively), whereas the intake of polyunsaturated fat was positively
      associated with tHcy concentrations only in the younger subjects (P for trend =
      0.03). The associations were weakened by additional adjustment for B vitamin
      intake but remained significant for SFA intake (P < 0.001). When stratified for
      total B vitamin intake, the inverse association between tHcy concentrations and
      very-long-chain n-3 FAs was significant only in the highest quartile of B vitamin
      intake (P for trend = 0.001), regardless of supplement use. CONCLUSIONS: High
      intakes of SFAs are associated with high plasma concentrations of tHcy. The
      inverse association between dietary intakes of very-long-chain n-3 FAs and plasma
      tHcy concentrations is apparent only at high B vitamin intakes.

PMID- 17556700
TI  - Whole-grain consumption is associated with a reduced risk of noncardiovascular,
      noncancer death attributed to inflammatory diseases in the Iowa Women's Health
      Study.
AB  - BACKGROUND: It has recently been shown that oxidative stress, infection, and
      inflammation are predominant pathophysiologic factors for several major diseases.
      OBJECTIVE: We investigated the association of whole-grain intake with death
      attributed to noncardiovascular, noncancer inflammatory diseases. DESIGN:
      Postmenopausal women (n = 41 836) aged 55-69 y at baseline in 1986 were followed
      for 17 y. After exclusions for cardiovascular disease, cancer, diabetes, colitis,
      and liver cirrhosis at baseline, 27 312 participants remained, of whom 5552 died
      during the 17 y. A proportional hazards regression model was adjusted for age,
      smoking, adiposity, education, physical activity, and other dietary factors.
      RESULTS: Inflammation-related death was inversely associated with whole-grain
      intake. Compared with the hazard ratios in women who rarely or never ate whole
      grain foods, the hazard ratio was 0.69 (95% CI: 0.57, 0.83) for those who
      consumed 4-7 servings/wk, 0.79 (0.66, 0.95) for 7.5-10.5 servings/wk, 0.64 (0.53,
      0.79) for 11-18.5 servings/wk, and 0.66 (0.54, 0.81) for >or=19 servings/wk (P
      for trend = 0.01). Previously reported inverse associations of whole-grain intake
      with total and coronary heart disease mortality persisted after 17 y of follow
      up. CONCLUSIONS: The reduction in inflammatory mortality associated with habitual
      whole-grain intake was larger than that previously reported for coronary heart
      disease and diabetes. Because a variety of phytochemicals are found in whole
      grains that may directly or indirectly inhibit oxidative stress, and because
      oxidative stress is an inevitable consequence of inflammation, we suggest that
      oxidative stress reduction by constituents of whole grain is a likely mechanism
      for the protective effect.

PMID- 17556701
TI  - Associations between markers of subclinical atherosclerosis and dietary patterns
      derived by principal components analysis and reduced rank regression in the Multi
      Ethnic Study of Atherosclerosis (MESA).
AB  - BACKGROUND: The association between diet and cardiovascular disease (CVD) may be
      mediated partly through inflammatory processes and reflected by markers of
      subclinical atherosclerosis. OBJECTIVE: We investigated whether empirically
      derived dietary patterns are associated with coronary artery calcium (CAC) and
      common and internal carotid artery intima media thickness (IMT) and whether prior
      information about inflammatory processes would increase the strength of the
      associations. DESIGN: At baseline, dietary patterns were derived with the use of
      a food-frequency questionnaire, and inflammatory biomarkers, CAC, and IMT were
      measured in 5089 participants aged 45-84 y, who had no clinical CVD or diabetes,
      in the Multi-Ethnic Study of Atherosclerosis. Dietary patterns based on
      variations in C-reactive protein, interleukin-6, homocysteine, and fibrinogen
      concentrations were created with reduced rank regression (RRR). Dietary patterns
      based on variations in food group intake were created with principal components
      analysis (PCA). RESULTS: The primary RRR (RRR 1) and PCA (PCA factor 1) dietary
      patterns were high in total and saturated fat and low in fiber and
      micronutrients. However, the food sources of these nutrients differed between the
      dietary patterns. RRR 1 was positively associated with CAC [Agatston score >0: OR
      (95% CI) for quartile 5 compared with quartile 1 = 1.34 (1.05, 1.71); ln(Agatston
      score = 1): P for trend = 0.023] and with common carotid IMT [>or=1.0 mm: OR (95%
      CI) for quartile 5 compared with quartile 1 = 1.33 (0.99, 1.79); ln(common
      carotid IMT): P for trend = 0.006]. PCA 1 was not associated with CAC or IMT.
      CONCLUSION: The results suggest that subtle differences in dietary pattern
      composition, realized by incorporating measures of inflammatory processes, affect
      associations with markers of subclinical atherosclerosis.

PMID- 17556702
TI  - Protein intake during the period of complementary feeding and early childhood and
      the association with body mass index and percentage body fat at 7 y of age.
AB  - BACKGROUND: A high protein intake during infancy and early childhood has been
      proposed to increase the risk of subsequent obesity. OBJECTIVE: We analyzed the
      association of different protein intakes during 6-24 mo with body mass index
      (BMI; in kg/m2) and percentage body fat (%BF) at 7 y of age. DESIGN: The analyses
      included 203 participants of the DOrtmund Nutritional and Longitudinally Designed
      (DONALD) Study with complete information on early diet (6, 12, and 18-24 mo) and
      anthropometric data at the age of 7 y. The median of energy-adjusted protein
      intakes (in g/d) was used to distinguish different patterns of low and high
      protein intakes throughout the first 2 y of life, which were then related to BMI
      SD scores (SDSs), %BF, and the risk of overweight and overfatness at 7 y of age.
      RESULTS: Although protein intake at 6 mo of age was not associated with the
      outcomes, a consistently high protein intake at the ages of 12 and 18-24 mo was
      independently related to a higher mean BMI SDS and %BF at the age of 7 y [BMI
      SDS: 0.37 (95% CI: 0.12, 0.61) compared with 0.08 (95% CI: -0.09, 0.26), P =
      0.04; %BF: 18.37 (95% CI: 17.29, 19.51%) compared with 16.91 (95% CI: 16.19,
      17.66%), P = 0.01] and a higher risk of having a BMI or %BF above the 75th
      percentile at that age [odds ratio for BMI: 2.39 (95% CI: 1.14, 4.99), P = 0.02);
      odds ratio for %BF: 2.28 (95% CI: 1.06, 4.88), P = 0.03]. CONCLUSIONS: High
      protein intakes during the period of complementary feeding and the transition to
      the family diet are associated with an unfavorable body composition at the age of
      7 y.

PMID- 17556703
TI  - Fruit and vegetable intakes, dietary antioxidant nutrients, and total mortality
      in Spanish adults: findings from the Spanish cohort of the European Prospective
      Investigation into Cancer and Nutrition (EPIC-Spain).
AB  - BACKGROUND: Epidemiologic data suggest that persons with diets rich in fruit and
      vegetables are at a lower risk of several chronic diseases and mortality than are
      persons with diets poor in fruit and vegetables. Often, this effect is attributed
      to antioxidant micronutrients found in plant foods. OBJECTIVE: We aimed to assess
      the relation of mortality to the consumption of fruit, vegetables, and other
      plant foods and to the dietary intake of vitamin C, vitamin E, and carotenoids.
      DESIGN: The study was a prospective study in the Spanish cohort of the European
      Prospective Investigation into Cancer and Nutrition. During 6.5 y of follow-up,
      562 deaths occurred in 41 358 subjects aged 30-69 y. Proportional hazards
      regression analysis was used to assess the relation between dietary factors and
      total mortality. RESULTS: After adjustment for age, sex, and several potential
      confounders, the hazard ratio for the highest versus the lowest quartile of
      consumption was 0.79 (95% CI: 0.62, 1.00; P for trend = 0.029) for fresh fruit,
      0.72 (0.56, 0.91; P for trend = 0.006) for root vegetables, and 0.77 (0.60, 0.98;
      P for trend = 0.015) for fruiting vegetables (ie, vegetables that contain the
      "fruit" part of the plant, the seeds). The corresponding figures for antioxidant
      nutrients were 0.74 (0.58, 0.94; P for trend = 0.009) for vitamin C, 0.68 (0.53,
      0.87; P for trend = 0.006) for provitamin A carotenoids, and 0.65 (0.51, 0.84; P
      for trend 0.001) for lycopene. The effect of vitamin C and provitamin A
      disappeared after adjustment for total antioxidant capacity in plant foods.
      CONCLUSIONS: A high intake of fresh fruit, root vegetables, and fruiting
      vegetables is associated with reduced mortality, probably as a result of their
      high content of vitamin C, provitamin A carotenoids, and lycopene. Antioxidant
      capacity could partly explain the effect of ascorbic acid and provitamin A but
      not the association with lycopene.

PMID- 17556704
TI  - Factors associated with overweight in preschool-age children in southwestern
      France.
AB  - BACKGROUND: Pediatric overweight and obesity are becoming an epidemic worldwide,
      which indicates the need for formulating preventive programs and policies during
      a child's early years. OBJECTIVE: We identified factors associated with
      overweight in young children in southwestern France. DESIGN: Children [n = 1780;
      x (+/-SD) age: 3.9 +/- 0.4 y] were recruited in kindergarten. Medical information
      on the parents, grandparents, and child as well as the child's 3-d dietary
      intake, participation in organized sports, and television-viewing habits were
      ascertained, and anthropometric measurements of the child were taken. RESULTS:
      The prevalence of overweight was 9.1% when using body mass index >or= 90th
      percentile of French reference curves as a cutoff. In a multivariate logistic
      regression, overweight at 4 y was associated with female sex, having an
      overweight mother, and having >or=1 diabetic grandparent; odds ratios (ORs; 95%
      CIs) for these variables were 1.9 (1.2, 3.0), 2.2 (1.0, 4.7), and 2.6 (1.6, 4.1),
      respectively. Being small or large for gestational age was not associated with
      the risk of overweight at 4 y, whereas this risk was increased for children who
      were overweight at 9 or 24 mo: ORs (95% CIs) were 4.0 (2.4, 6.9) and 11.7 (6.1,
      22.2), respectively. Nutrient intakes did not differ significantly with weight
      status in girls; however, overweight boys had significantly greater energy and
      lipid intakes than did their nonoverweight counterparts. Overweight was
      positively associated with television viewing (>1 h/d) in both sexes and with
      participation in organized sports in girls only. CONCLUSIONS: A family history of
      overweight or diabetes, overweight in the first 2 y of life, and television
      viewing are associated with overweight at 4 y. These factors should be considered
      in developing programs for the prevention of overweight in early childhood.

PMID- 17556705
TI  - Dietary patterns and blood pressure change over 5-y follow-up in the SU.VI.MAX
      cohort.
AB  - BACKGROUND: Although short-term effects of the Dietary Approaches to Stop
      Hypertension (DASH) diet on blood pressure have been shown in intervention
      studies, less is known about the long-term effects. OBJECTIVE: The aim was to
      study the relation between dietary patterns based on DASH diet characteristics
      and blood pressure (BP) and BP change in a clinical trial of antioxidants
      conducted in France from 1994 to 2002. DESIGN: Repeated 24-h dietary records were
      collected during the first year of follow-up. Dietary variables studied included
      fruit and vegetables, dairy products and fat (defined by Keys score), and two
      hypothesis-oriented scores based on the DASH diet. We performed a cross-sectional
      analysis of BP measured at the first clinical examination (1995-1996) in 4652
      participants aged 35-63 y and a longitudinal analysis of BP change over a median
      follow-up of 5.4 y (n = 2341). RESULTS: The mean increases in systolic (SBP) and
      diastolic (DBP) BPs were 9.3 and 4.5 mm Hg, respectively. After adjustment for
      potential confounders, higher fruit and vegetable consumption was associated with
      lower SBP and DBP at first clinical examination (P for trend < 0.02 for both) and
      a lower 5-y increase in SBP (-2.1 mm Hg in the 4th compared with the 1st
      quartile; P for trend < 0.004) and DBP (-0.7 mm Hg in the 4th compared with the
      1st quartile; P for trend < 0.03). The 2 DASH scores also were significantly
      associated with a lower BP at the first clinical examination and a lower BP
      increase. No significant relations were observed with dairy products or Keys
      score in either analyses. CONCLUSION: These results suggest that high fruit and
      vegetable intakes may be associated with a lower increase in BP with aging.

PMID- 17556706
TI  - Racial differences in skeletal calcium retention in adolescent girls with varied
      controlled calcium intakes.
AB  - BACKGROUND: Higher bone mass in blacks than in whites has been related to greater
      calcium utilization efficiency. Dietary calcium requirements for maximal skeletal
      calcium accretion during puberty may differ between the races. OBJECTIVE: This
      study compared the relation between calcium intake and calcium retention in black
      and white adolescent girls. DESIGN: A range of controlled calcium intakes (760
      1981 mg Ca/d) were used in 3-wk controlled balance studies. Some subjects were
      studied more than once; a total of 182 observations from 55 black girls and 66
      white girls were analyzed. RESULTS: Blacks had 185 +/- 32 mg/d greater mean
      skeletal calcium retention than did whites (P < 0.0001) at all calcium intakes as
      a result of significantly greater net calcium absorption (P < 0.001) and lower
      calcium excretion (P < 0.0001). CONCLUSIONS: Dietary calcium requirements did not
      differ with race. Higher calcium retention at all calcium intakes during
      adolescence may underlie the higher bone mineral content of adult blacks than of
      adult whites.

PMID- 17556707
TI  - Postprandial nitrogen utilization and misinterpretation of data.

PMID- 17556708
TI  - Is depression a low-grade systemic inflammatory condition?

PMID- 17556709
TI  - Dietary protein, growth factors, and cancer.

PMID- 17556710
TI  - Adipocyte differentiation induced using nonspecific siRNA controls in cultured
      human mesenchymal stem cells.
AB  - RNA interference (RNAi) is gene silencing induced by double-stranded RNA of 21-23
      nucleotides in length, termed small interfering RNA, or siRNA. RNAi-based
      techniques have been widely applied to elucidate gene function, identify drug
      targets, and used in trials as a promising adjunct to silence disease-causing
      genes. However, emerging evidence suggests unexpected changes in expression of
      untargeted genes as a consequence of an off-target effect by RNAi in mammalian
      cells. To date, our understanding of such effects on stem cells is limited. We
      transfected human fetal femur-derived mesenchymal stem cells using commercially
      available nonspecific siRNA controls and examined adipocyte differentiation in
      the cells using morphology, histochemistry, and quantitative real-time PCR to
      examine the expression of key genes for adipogenic or osteogenic differentiation.
      We report here the induction of adipocyte differentiation in human mesenchymal
      stem cells using nonspecific siRNAs raising concerns as to the specificity of
      RNAi in stem cells and, critically, a need to understand and delineate the rules
      governing the specificity of RNAi.

PMID- 17556711
TI  - Using 5'-PTMs to repair mutant beta-globin transcripts.
AB  - Trans-splicing has been used to repair mutant RNA transcripts via competition for
      the spliceosome using pre-trans-splicing molecules, or "PTMs." Previous studies
      have demonstrated that functional PTMs can be designed for either 3'- or 5'-exon
      replacement, with a vast majority of the work to date focusing on repair of
      mutations within internal exons and via 3'-exon replacement. Here, we describe
      the first use of trans-splicing to target the first exon and intron of a
      therapeutically relevant gene and repair the mutant RNA by 5'-exon replacement.
      Our results show that 5'-PTMs can be designed to repair mutations in the beta
      globin transcript involved in sickle cell anemia and beta-thalassemia while
      providing insight into considerations for competition between trans- versus cis
      splicing in mammalian cells. Target transcripts with impaired cis-splicing
      capabilities, like those produced in some forms of beta-thalassemia, are more
      efficiently repaired via trans-splicing than targets in which cis-splicing is
      unaffected as with sickle beta-globin. This study reveals desirable
      characteristics in substrate RNAs for trans-splicing therapeutics as well as
      provides an opportunity for further exploration into general splicing mechanisms
      via 5'-PTMs.

PMID- 17556712
TI  - Efficiency of a self-aminoacylating ribozyme: effect of the length and base
      composition of its 3' extension.
AB  - Variants of a previously described small self-aminoacylating ribozyme are tested
      in order to uncover the potentialities of a 3' extension responsible for the
      esterification. The base-composition and the length of this specific part of the
      ribozyme are investigated. Very short extensions can still reach the active site,
      reflecting the small persistence length of RNA. The yield of aminoacylation is
      particularly high for ribozymes with extensions made up of a poly-U, for which a
      maximum of efficiency is observed for a total length of about 10 nucleotides. A
      simple model describing the behavior of this region of the ribozyme can account
      for the data.

PMID- 17556713
TI  - Prolonged respiratory symptoms in clean-up workers of the prestige oil spill.
AB  - RATIONALE: The wreckage of the oil tanker Prestige in November 2002 produced
      heavy contamination off the coast of Galicia, Spain. OBJECTIVES: To evaluate the
      prevalence of respiratory symptoms in local fishermen more than 1 year after
      having participated in clean-up work. METHODS: Questionnaires including
      qualitative and quantitative information about clean-up activities and
      respiratory symptoms were distributed among associates of 38 fishermen's
      cooperatives. Both postal and telephone follow-up was performed. The association
      between participation in clean-up work and respiratory symptoms was evaluated
      using multiple logistic regression analyses, adjusted for sex, age, and smoking
      status. MEASUREMENTS AND MAIN RESULTS: Between January 2004 and February 2005,
      data were obtained from 6,780 fishermen (response rate, 76%). Sixty-three percent
      had participated in clean-up operations. Lower respiratory tract symptoms (LRTS)
      were more prevalent in clean-up workers: odds ratio (OR), 1.73; 95% confidence
      interval (CI), 1.54-1.94. This association was consistent for men and women, for
      different fishermen's cooperatives, and for different types of respiratory
      symptoms, and remained after excluding those who reported anxiety or believed
      that the oil spill had affected their health (OR, 1.57; 95% CI, 1.37-1.80). The
      risk of LRTS increased with the number of exposed days, exposed hours per day,
      and number of activities (linear trend, P < 0.0001). The excess risk of LRTS
      decreased when more time had elapsed since last exposure: OR, 2.33, 1.69, and
      1.24 for less than 14 months, 14-20 months, and more than 20 months,
      respectively. CONCLUSIONS: Participation in clean-up work of oil spills may
      result in prolonged respiratory symptoms that last 1 to 2 years after exposure.

PMID- 17556714
TI  - The role of the social environment in children and adolescents with asthma.
AB  - RATIONALE: Biopsychosocial models of asthma have been proposed in the literature,
      but few empirical tests of social factors at various levels of influence have
      been conducted. OBJECTIVES: To test associations of neighborhood, peer, and
      family factors with asthma outcomes in youth, and to determine the pathways
      through which these social factors operate. METHODS: Observational study of
      youths with asthma (n = 78). MEASUREMENTS AND MAIN RESULTS: Youths completed
      questionnaires about neighborhood problems, peer support, and family support.
      Biological (IgE, eosinophil count, production of IL-4) and behavioral (youth
      smoking, exposure to smoke, adherence to medications) pathways were measured.
      Asthma symptoms and pulmonary function were assessed in the laboratory and at
      home for 2 weeks. Lower levels of family support were associated with greater
      symptoms (beta coefficients: -0.26 to -0.33, P < 0.05) and poorer pulmonary
      function (beta: 0.30, P < 0.05) via biological pathways (Z statistics from 1.19
      to 1.51, P < 0.05). Higher levels of neighborhood problems were associated with
      greater symptoms (beta coefficients: 0.27-0.33, P < 0.05) via behavioral pathways
      related to smoking (Z statistics = 1.40, P < 0.05). Peer support was not
      associated with symptoms or pulmonary function. CONCLUSIONS: This study indicates
      that family factors may affect youths' asthma via physiologic changes, whereas
      community factors may help shape the health behaviors of youths with asthma.

PMID- 17556715
TI  - Novel recombinant interleukin-13 peptide-based vaccine reduces airway allergic
      inflammatory responses in mice.
AB  - RATIONALE: Interleukin (IL)-13 plays a pivotal role in the pathogenesis of
      allergic asthma. Passive administration of its monoclonal antibody or soluble
      receptor to block overproduced IL-13 has been proven to be effective in
      controlling airway allergic responses in animal models, but these approaches have
      disadvantages of short half-lives, high costs, and possible adverse effects.
      OBJECTIVES: We sought to develop a novel therapeutic strategy through
      constructing an IL-13 peptide-based vaccine for blocking IL-13 on a persistent
      effect basis and to evaluate its in vivo effects using a murine model. METHODS:
      To break self-tolerance, truncated hepatitis B core antigen was used as a
      carrier. Vaccine was prepared by inserting a peptide derived from the receptor
      binding site of mouse IL-13 into the immunodominant epitope region of the carrier
      using gene recombination methods. Mice received vaccine subcutaneously three
      times, and then subjected to intraperitoneal sensitization and intranasal
      challenge with ovalbumin. Control animals received carrier or saline in place of
      vaccine. MEASUREMENTS AND MAIN RESULTS: The vaccine presented as virus-like
      particles and induced sustained and high titered IL-13-specific IgG without the
      use of conventional adjuvant. Vaccination significantly suppressed ovalbumin
      induced inflammatory cell number, and IL-13 and IL-5 levels in bronchoalveolar
      lavage fluids. Serum total and ovalbumin-specific IgE were also significantly
      inhibited. Moreover, allergen-induced goblet cell hyperplasia, lung tissue
      inflammatory cell infiltration, and pulmonary hyperresponsiveness to inhaled
      methacholine were significantly suppressed in vaccinated mice. CONCLUSIONS: Our
      data indicate that IL-13 peptide-based vaccines could be an effective therapeutic
      approach in the treatment of asthma.

PMID- 17556716
TI  - Glycogen synthase kinase-3beta inhibition attenuates asthma in mice.
AB  - RATIONALE: Persistent activation of nuclear factor-kappaB has been associated
      with the development of asthma. Glycogen synthase kinase-3beta is known to
      regulate the activity of nuclear factor-kappaB. OBJECTIVES: We hypothesized that
      inhibition of glycogen synthase kinase-3beta may have anti-inflammatory effects
      in allergic asthma. METHODS: BALB/c mice sensitized and challenged with ovalbumin
      developed airway inflammation. Bronchoalveolar lavage fluid was assessed for
      total and differential cell counts, and for cytokine and chemokine levels. Lung
      tissues were examined for cell infiltration and mucus hypersecretion, and for the
      expression of inflammatory biomarkers. Serum immunoglobulin E levels were
      determined by enzyme-linked immunosorbant assay. Airway hyperresponsiveness was
      monitored by direct airway resistance analysis. MEASUREMENTS AND MAIN RESULTS:
      Intravenous administration of 4-benzyl-2-methyl-1,2,4-thiadiazolidine-3,5-dione
      (TDZD-8), a selective glycogen synthase kinase-3beta inhibitor, significantly
      inhibited ovalbumin-induced increases in total cell counts, eosinophil counts,
      and IL-5, IL-13, and eotaxin levels recovered in bronchoalveolar lavage fluid in
      a dose-dependent manner. TDZD-8 substantially reduced the serum levels of
      ovalbumin-specific IgE. Histologic studies showed that TDZD-8 dramatically
      inhibited ovalbumin-induced lung tissue eosinophilia and airway mucus production.
      TDZD-8 also markedly suppressed ovalbumin-induced mRNA expression of
      intercellular adhesion molecule-1, vascular cell adhesion molecule-1, Muc5ac, and
      three members of the chitinase family (acidic mammalian chitinase, Ym1, and Ym2).
      In addition, TDZD-8 significantly reduced ovalbumin-induced airway
      hyperresponsiveness to inhaled methacholine. Western blot analysis of whole lung
      lysates revealed that TDZD-8 markedly attenuated the phosphorylation of the
      nuclear factor-kappaB subunit p65 from ovalbumin-challenged mice. CONCLUSIONS:
      Our findings suggest that inhibition of glycogen synthase kinase-3beta may
      provide a novel means for the treatment of allergic airway inflammation.

PMID- 17556717
TI  - Electroporation-mediated gene transfer of the Na+,K+ -ATPase rescues endotoxin
      induced lung injury.
AB  - RATIONALE: Acute lung injury and acute respiratory distress syndrome are common
      clinical syndromes resulting largely from the accumulation of and inability to
      clear pulmonary edema, due to injury to the alveolar epithelium. Gene therapy may
      represent an important alternative for the treatment and prevention of these
      diseases by restoring alveolar epithelial function. We have recently developed an
      electroporation strategy to transfer genes to the lungs of mice, with high
      efficiency and low inflammation. OBJECTIVES: We asked whether electroporation
      mediated transfer of genes encoding subunits of the Na+,K+ -ATPase could protect
      from LPS-induced lung injury or be used to treat already injured lungs by up
      regulating mechanisms of pulmonary edema clearance. METHODS: Plasmids were
      delivered to the lungs of mice using transthoracic electroporation. Lung injury
      was induced by intratracheal administration of LPS (4 mg/kg body weight).
      Biochemical, cellular, and physiologic measurements were taken to assess gene
      transfer and lung injury. MEASUREMENTS AND MAIN RESULTS: Improvements in wet-to
      dry ratios, pulmonary effusions, bronchoalveolar lavage protein levels and
      cellularity, alveolar fluid clearance, and respiratory mechanics were seen after
      delivery of plasmids expressing Na+,K+ -ATPase subunits, but not control
      plasmids, in LPS-injured lungs. Delivery of plasmids expressing Na+,K+ -ATPase
      subunits both protected from subsequent lung injury and partially reversed
      existing lung injury by these measures. CONCLUSIONS: These results demonstrate
      that electroporation can be used effectively in healthy and injured lungs to
      facilitate gene delivery and expression. To our knowledge, this is the first
      successful use of gene delivery to treat existing lung injury, and may have
      future clinical potential.

PMID- 17556718
TI  - Effects of continuous positive airway pressure on early signs of atherosclerosis
      in obstructive sleep apnea.
AB  - RATIONALE: Obstructive sleep apnea (OSA) is associated with adverse
      cardiovascular outcomes, including myocardial infarction and stroke.
      Atherosclerosis is a key mechanism for these cardiovascular events. Recent cross
      sectional studies showed the presence of early signs of atherosclerosis in
      patients with OSA who were free of comorbidities. OBJECTIVES: To determine the
      impact of treatment with continuous positive airway pressure (CPAP) on
      atherosclerosis. METHODS: We randomly assigned 24 patients with severe OSA (age,
      46 +/- 6 yr) who were free of comorbidities to receive no treatment (control, n =
      12) or CPAP (n = 12) for 4 months. Carotid intima-media thickness, arterial
      stiffness (evaluated by pulse-wave velocity), carotid diameter, 24-hour blood
      pressure monitoring, C-reactive protein, and catecholamines were determined at
      baseline and after 4 months. MEASUREMENTS AND MAIN RESULTS: At baseline, all
      measurements were similar in both groups and did not change in the control group
      after 4 months. In contrast, a significant decrease occurred in carotid intima
      media thickness (707 +/- 105 vs. 645 +/- 95 microm, P = 0.04), pulse-wave
      velocity (10.4 +/- 1.0 vs. 9.3 +/- 0.9 m/s, P < 0.001), C-reactive protein (3.7
      +/- 1.8 vs. 2.0 +/- 1.2 mg/L, P = 0.001), and catecholamines (365 +/- 125 vs. 205
      +/- 51 ng/ml, P < 0.001) after 4 months of CPAP. Carotid diameter did not change
      significantly. Regarding the whole group, changes in carotid intima-media
      thickness were correlated with changes in catecholamines (r = 0.41, P < 0.05).
      Changes in pulse-wave velocity were correlated with changes in C-reactive protein
      (r = 0.58, P < 0.01) and catecholamines (r = 0.54, P < 0.01). CONCLUSIONS: The
      treatment of OSA significantly improves early signs of atherosclerosis,
      supporting the concept that OSA is an independent risk factor for
      atherosclerosis. Clinical trial registered with www.clinicaltrials.gov (NCT
      00400543).

PMID- 17556719
TI  - Six-second spirometry for detection of airway obstruction: a population-based
      study in Austria.
AB  - RATIONALE: The presence of airway obstruction is currently defined by Global
      Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines on the basis of
      the post-bronchodilator (BD) FEV(1)/FVC. It has been proposed that the
      traditional FVC can be replaced with the shorter and less demanding FEV(6) for
      detecting airway obstruction. OBJECTIVES: A comparison of FEV(1)/FVC and
      FEV(1)/FEV(6) for the detection of airway obstruction in population-based post
      bronchodilator spirometry data. METHODS: A population-based sample of 1,349
      adults participated in the Burden of Obstructive Lung Disease study in Austria.
      Specially trained and certified technicians conducted pre-BD and post-BD
      spirometry according to American Thoracic Society guidelines and administered
      standardized questionnaires. A total of 93% of the post-BD test sessions were
      acceptable, and were included in this analysis. The Third National Health and
      Nutrition Examination Survey reference equations were used to calculate predicted
      values and lower limits of normal (LLN) for FEV(1), FEV(6), FVC, FEV(1)/FVC, and
      FEV(1)/FEV(6). MEASUREMENTS AND MAIN RESULTS: The post-BD FEV(1)/FVC was below
      the LLN in 199 (15.8%) subjects. The sensitivity of the FEV(1)/FEV(6) for airway
      obstruction depended greatly on the threshold of percent predicted FEV(1) also
      used in the definition. The overall sensitivity of FEV(1)/FEV(6) for a diagnosis
      of airway obstruction, as defined by FEV(1)/FVC (including participants with an
      FEV(1) above the LLN), was 72.9%, with 98.8% specificity. The sensitivity
      increased to 98.0% when a low FEV(1) was also required to diagnose post-BD airway
      obstruction. The discordant cases had long forced expiratory times, often showed
      a flow-volume curve pattern consistent with two-compartment emptying, and were
      more often never-smokers. CONCLUSIONS: Six-second spirometry maneuvers (which
      measure FEV(6)) are as sensitive and specific for post-BD airway obstruction as
      traditional (prolonged exhalation time) FVC maneuvers only when the definition of
      airway obstruction includes a low FEV(1).

PMID- 17556720
TI  - Idiopathic nonspecific interstitial pneumonia: lung manifestation of
      undifferentiated connective tissue disease?
AB  - RATIONALE: The American Thoracic Society/European Respiratory Society
      International Consensus Classification panel identified the clinical entity
      idiopathic nonspecific interstitial pneumonia (NSIP) as a provisional diagnosis
      and recommended further study. OBJECTIVES: We hypothesized that idiopathic NSIP
      is an autoimmune disease and the lung manifestation of undifferentiated
      connective tissue disease (UCTD), a recently described, distinct entity. METHODS:
      We studied 28 consecutive patients with idiopathic interstitial pneumonia (IIP)
      enrolled in the University of California, San Francisco Interstitial Lung Disease
      Center who met prespecified criteria for UCTD, as follows: at least one clinical
      manifestation of connective tissue disease, serologic evidence of systemic
      inflammation in the absence of clinical infection, and absence of sufficient
      American College of Rheumatology criteria for another connective tissue disease.
      Medical record reviews, evaluation of radiographs, and scoring of lung biopsies
      were performed. The control group consisted of all other patients (n = 47) with
      IIP who did not meet the UCTD criteria. MEASUREMENTS AND MAIN RESULTS: The
      patients with UCTD were more likely to be women, younger, and nonsmokers than the
      IIP control subjects. Compared with the control group, patients with UCTD-ILD
      were significantly more likely to have ground-glass opacity on high-resolution
      computed tomography (HRCT) and NSIP pattern on biopsy, and less likely to have
      honeycombing on HRCT or usual interstitial pneumonia on biopsy. At our center,
      the majority of patients classified as idiopathic NSIP (88%) met the criteria for
      UCTD. CONCLUSIONS: Most patients diagnosed with idiopathic NSIP meet the case
      definition of UCTD. Furthermore, these results show that the clinical entity
      idiopathic NSIP is different from idiopathic pulmonary fibrosis and appears to be
      an autoimmune disease.

PMID- 17556721
TI  - Effect of intensive care unit organizational model and structure on outcomes in
      patients with acute lung injury.
AB  - RATIONALE: Prior studies supported an association between intensive care unit
      (ICU) organizational model or staffing patterns and outcome in critically ill
      patients. OBJECTIVES: To examine the association of closed versus open models
      with patient mortality across adult ICUs in King County (WA). METHODS: Cohort
      study of patients with acute lung injury (ALI). MEASUREMENTS AND MAIN RESULTS:
      ICU structure, organization, and patient care practices were assessed using self
      administered mail questionnaires completed by the medical director and nurse
      manager. We defined closed ICUs as units that required patient transfer to or
      mandatory patient comanagement by an intensivist and open ICUs as those relying
      on other organizational models. Outcomes were obtained from the King County Lung
      Injury Project, a population-based cohort of patients with ALI. The main endpoint
      was hospital mortality. Of 24 eligible ICUs, 13 ICUs were designated closed and
      11 open. Complete survey data were available for 23 (96%) ICUs. Higher physician
      and nurse availability was reported in closed versus open ICUs. A total of 684 of
      1,075 (63%) of patients with ALI were cared for in closed ICUs. After adjusting
      for potential confounders, patients with ALI cared for in closed ICUs had reduced
      hospital mortality (adjusted odds ratio, 0.68; 95% confidence interval, 0.53,
      0.89; P = 0.004). Consultation by a pulmonologist in open ICUs was not associated
      with improved mortality (adjusted odds ratio, 0.94; 95% confidence interval,
      0.74, 1.20; P = 0.62). These findings were robust for varying assumptions about
      the study population definition. CONCLUSIONS: Patients with ALI cared for in a
      closed-model ICU have reduced mortality. These data support recommendations to
      implement structured intensive care in the United States.

PMID- 17556722
TI  - Prophylactic heparin in patients with severe sepsis treated with drotrecogin alfa
      (activated).
AB  - RATIONALE: Patients with severe sepsis frequently receive prophylactic heparin
      during drotrecogin alfa (activated) (DrotAA) treatment due to risk of venous
      thromboembolic events (VTEs). Biological plausibility exists for heparin to
      reduce DrotAA efficacy and/or increase bleeding. OBJECTIVES: Primary: demonstrate
      in adult patients with severe sepsis receiving DrotAA treatment that 28-day
      mortality was equivalent for patients treated with concomitant prophylactic
      heparin compared with placebo; secondary: safety and VTE incidence. METHODS:
      International, randomized, double-blind, phase 4, equivalence-design trial (n =
      1994). Patients were eligible if indicated for and receiving DrotAA treatment
      under the country's approved label. Study drug (low molecular
      weight/unfractionated heparin) or placebo (saline) was administered every 12
      hours during DrotAA infusion (24 ug/kg/hr for 96 hr). In patients on baseline
      heparin and randomized to placebo, heparin was stopped. MEASUREMENTS AND MAIN
      RESULTS: Twenty-eight-day mortality was not equivalent between treatment groups.
      Heparin mortality was numerically lower (28.3 vs. 31.9%; p = 0.08). In the
      prospectively defined subgroup of patients exposed to heparin at baseline,
      patients receiving placebo experienced higher mortality (35.6 vs. 26.9%; p =
      0.005). For safety, significant differences were observed during Days 0-6 for any
      bleeding event (placebo, n = 78; heparin, n = 105; p = 0.049) and ischemic stroke
      during Days 0-6 (placebo, n = 12; heparin, n = 3; p = 0.02) and Days 0-28
      (placebo, n = 17; heparin, n = 5; p = 0.009). The VTE rate was low, with no
      statistical difference between groups (0-6 d, p = 0.60; 0-28 d, p = 0.26).
      CONCLUSIONS: Compared with placebo, concomitant prophylactic heparin was not
      equivalent, did not increase 28-day mortality, and had an acceptable safety
      profile in patients with severe sepsis receiving DrotAA. Heparin discontinuation
      should be carefully weighed in patients considered for DrotAA treatment. XPRESS
      clinical trial registered with www.clinicaltrials.gov (NCT 00049777). The study
      ID numbers are 6743; F1K-MC-EVBR.

PMID- 17556723
TI  - Survival after lung volume reduction in chronic obstructive pulmonary disease:
      insights from small airway pathology.
AB  - RATIONALE: COPD is associated with reduced life expectancy. OBJECTIVES: To
      determine the association between small airway pathology and long-term survival
      after lung volume reduction in chronic obstructive pulmonary disease (COPD) and
      the effect of corticosteroids on this pathology. METHODS: Patients with severe
      (GOLD-3) and very severe (GOLD-4) COPD (n = 101) were studied after lung volume
      reduction surgery. Respiratory symptoms, quality of life, pulmonary function,
      exercise tolerance, chest radiology, and corticosteroid treatment status were
      assessed preoperatively. The severity of luminal occlusion, wall thickening, and
      the presence of small airways containing lymphoid follicles were determined in
      resected lung tissue. Kaplan-Meier survival analysis and Cox proportional hazards
      models were used to determine the relationship between survival and small airway
      pathology. The effect of corticosteroids on this pathology was assessed by
      comparing treated and untreated groups. MEASUREMENTS AND MAIN RESULTS: The
      quartile of subjects with the greatest luminal occlusion, adjusted for
      covariates, died earlier than subjects who had the least occlusion (hazard ratio,
      3.28; 95% confidence interval, 1.55-6.92; P = 0.002). There was a trend toward a
      reduction in the number of airways containing lymphoid follicles (P = 0.051) in
      those receiving corticosteroids, with a statistically significant difference
      between the control and oral +/- inhaled corticosteroid-treated groups (P =
      0.019). However, corticosteroid treatment had no effect on airway wall thickening
      or luminal occlusion. CONCLUSIONS: Occlusion of the small airways by inflammatory
      exudates containing mucus is associated with early death in patients with severe
      emphysema treated by lung volume reduction surgery. Corticosteroid treatment
      dampens the host immune response in these airways by reducing lymphoid follicles
      without changing wall thickening and luminal occlusion.

PMID- 17556724
TI  - Periodontal healing following orthodontic movement of rat molars with intact
      versus damaged periodontia towards a bony defect.
AB  - The aim of this research was to determine whether orthodontic tooth movement
      influences periodontal healing. In 16 male Wistar rats, 12 week of age, a bony
      defect was created mesial to both maxillary first molars, not including the
      attachment apparatus (group 1), and in 15 animals, the defect included the
      periodontal ligament (group 2). In both groups, the right first molar was moved
      mesially (orthodontic side) for 2 weeks followed by a 1-week retention period;
      the contralateral molar was not moved (control side). Histomorphometric analysis
      was performed. The results within and between the different treatment groups and
      sides were statistically compared by t-test and analysis of variance with
      repeated measures on logarithmic transformation. Junctional epithelium was
      significantly larger at the control than at the orthodontic side of both groups
      (P = 0.024), and significantly larger in group 2 than in group 1 (P < 0.001). A
      significantly (P = 0.034) larger pocket depth was found at the control side in
      group 1. Supracrestal connective tissue was larger at the control than at the
      orthodontic side for both groups and significantly larger in group 2 than in
      group 1 (P = 0.004). Root resorption was found infrequently only at the
      orthodontic side in both groups (five out of 31 cases). The principal findings
      suggest favourable effects of orthodontic tooth movement on restraining
      epithelial apical down-growth and decreasing pocket depth. Orthodontic treatment
      could not completely avoid formation of a long epithelial attachment. Therefore,
      periodontal regenerative surgery might be indicated prior to orthodontic tooth
      movement. Orthodontic movement, shortly after periodontal surgery, had no
      detrimental effect on periodontal soft tissue healing or on diminished but non
      inflamed periodontal tissues.

PMID- 17556725
TI  - A new idea and method of tooth movement using a ratchet bracket.
AB  - Since ideally effective tooth movement in orthodontics should occur without
      causing damage to the periodontal ligament (PDL), a new bracket with a ratchet
      locking system, the 'Ratchet Bracket', was designed to produce tooth movement
      while maintaining blood circulation. To define the mechanism of the appliance, a
      histological study was carried out on four Beagle dogs (9 months old) and a
      clinical study on five female patients (11 years to 38 years 10 months of age).
      Five upper canines in the dogs were moved 1.82 mm per month. On light microscopic
      observations, vascular forms showed a round-oval shape, without undermining bone
      resorption. No root resorption was observed in the compressed PDL at days 1, 14,
      and 35 of the experimental period. On fluorescent images at day 46, distinctive
      bone formation was apparent at the tension side. In the clinical investigation,
      nine upper canines in the five female patients were moved 1.92 mm per month. A
      wide and long alveolar hard line was seen only on the tension side of the canines
      on dental radiographs, indicating bodily tooth movement, without obvious signs of
      root resorption in all subjects. Neither spontaneous pain nor pain during biting
      were reported. The findings indicate that use of the ratchet bracket could result
      in rapid and pain-free tooth movement with vascular clarity to maintain blood
      circulation in the PDL.

PMID- 17556726
TI  - Craniofacial morphology in patients with sickle cell disease: a cephalometric
      analysis.
AB  - The aim of the study was to evaluate the craniofacial morphology in Caucasian
      patients with sickle cell disease (SCD) by comparing them with a healthy group
      paired for gender and age, by means of lateral cephalometric radiographs. Thirty
      six Sicilian patients with SCD (17 females and 19 males), including 14
      beta(s)beta(s) (mean age 28 +/- 5.9 years), 13 beta(s)beta(0 th) (mean age 27.5
      +/- 8 years), and nine beta(s)beta(+th) (mean age 32.8 +/- 9.9 years) were
      examined. The control group consisted of 36 subjects (mean age 28.9 +/- 8 years)
      without recognized haematological abnormalities. The means and standard
      deviations were calculated for each cephalometric variable. A two-sample t-test
      was used to compare the means between the study and control groups. One-way
      analysis of variance and Dunnet's multiple comparison test were used in order to
      analyse the differences between the control group and the subgroups divided
      according to genotype. The level of significance used was P<0.05. The
      cephalometric findings indicated a posterior rotation of the mandible and a
      tendency towards a vertical pattern (clockwise), with lower (P=0.000) and total
      (P=0.002) face heights increased in comparison with the control sample. These
      findings were more pronounced in subjects with SCD (beta(s)beta(s)). In all
      patients, there was a significantly greater maxillary incisor proclination than
      in the control group. The upper first molar position to the PTV line was
      significantly increased but only in patients with compound heterozygosis
      beta(s)beta(th). The SCD patients did not exhibit the craniofacial abnormalities
      noted in black American patients with SCD; the craniofacial features observed,
      reflecting the degree of clinical expression of SCD in Sicilian patients, were of
      moderate severity.

PMID- 17556727
TI  - Comparison of nasal volume changes during rapid maxillary expansion using
      acoustic rhinometry and computed tomography.
AB  - The purpose of this study was to compare nasal volume changes using acoustic
      rhinometry (AR) and computed tomography (CT). The subjects were 10 children (6
      girls and 4 boys, with an age range of 12-14 years) who required rapid maxillary
      expansion (RME) on the basis of their individual malocclusion. All patients were
      found to have normal nasal cavities following anterior rhinoscopic examination.
      AR and CT were undertaken at the start of treatment (t(1)) and 6 months after
      expansion (t(2)). Volume changes due to expansion were evaluated using Wilcoxon's
      test, and the correlation between the two methods was assessed with correlation
      analyses. Both methods demonstrated that nasal volume significantly increased
      following the use of RME (P<0.05). Correlation analyses showed no difference in
      volume (P>0.05) using either of the two methods.

PMID- 17556728
TI  - Neurosensory and functional impairment in sagittal split osteotomies: a
      longitudinal and long-term follow-up study.
AB  - The aim was to conduct a long-term follow-up study on the function and
      sensitivity of the mandible in advancement and setback patients after bilateral
      sagittal split osteotomy (BSSO) with rigid internal fixation. The advancement and
      setback groups consisted of 16 (12 females and 4 males, mean age: 21.4 and 21.3
      years, respectively) and 17 (11 females and 6 males, mean age: 27.1 and 27.7
      years, respectively). The final follow-up was a mean of 12.7 years (T4) post
      operatively. The other follow-up examinations were before surgery (T1) and
      7.3/6.6 (T2) and 13.9/14.4 (T3) months after surgery. To evaluate
      craniomandibular function, mouth-opening capacity, laterotrusion, protrusion,
      deviations during opening, pain and clicking of the temporomandibular joint
      (TMJ), muscular pain, and the retruded contact position-intercuspal position (RC
      IP) distance were examined. A questionnaire was used to record subjective
      reports. The neurosensory status was determined with two-point discrimination (2
      pd), the pointed, blunt, and light-touch tests. Statistical analysis included the
      following tests: Wilcoxon signed ranked matched pairs, Mann-Whitney U, paired t,
      and Fisher's exact test. Bonferroni's adjustments were made for evaluation of the
      questionnaire and Spearman's rank correlation coefficients to determine the
      interdependence of selected variables. Craniomandibular function showed
      restitution at T4 after 12.7 years. The 2-pd at the lip and chin had largely
      normalized in the two groups at T3. At T4, there was a significant increase of 2
      pd at the lip and chin in both groups. The discrimination between sharp and blunt
      was limited in both groups in 25 per cent of patients at T4. Dysfunctions such as
      TMJ clicking, bruxism, and pain in the TMJ and muscles were neither increased nor
      decreased after BSSO. The initial post-surgical neurosensory impairment was
      barely detectable 1 year post-surgery. The new neurosensory impairment manifested
      at T4 was probably due to the normal human process of ageing. Neither age,
      gender, surgical advancement, nor setback showed any significant correlations.

PMID- 17556729
TI  - Stepwise advancement versus maximum jumping with headgear activator.
AB  - The aim of this study was to compare the effects of stepwise mandibular
      advancement versus maximum jumping and extended treatment versus early retention.
      The material was obtained prospectively and consisted of lateral cephalograms
      taken at the start (T0), after initial (T1), and at the end (T2) of treatment,
      from two groups of consecutively treated skeletal Class II patients who had
      undergone therapy with headgear activators. The first headgear activator group,
      HGA-S (n=24; mean age 11.9 +/- 1.2 years), was treated for 13 months and had 4-mm
      mandibular advancement every 3 months. The second headgear activator group, HGA-M
      (n=31; mean age 11.2 +/- 1.5 years), had maximum jumping, 6-8 mm interincisal
      opening, for a total of 15.4 months, and with reduced wear for the last 6.9
      months. The dropout over 12 months was 41 and 46 per cent, respectively. Pre
      treatment growth changes were obtained as a reference. An independent t-test was
      used to determine differences in baseline dentofacial morphology between the
      groups, a paired t-test for intra-group comparisons, and an independent t-test to
      evaluate differences between the groups. The results, in both groups, showed
      enhanced mandibular prognathism during the initial phase (T0-T1), followed by
      normal growth (T1-T2), and lower face height enhancement throughout treatment (T0
      T2). For both groups, the mandibular plane and occlusal angle increased, possibly
      enhanced by 'extrusion' of the lower molars. For both groups, maxillary forward
      growth was restrained only during the initial phase, but the effect remained
      significant at T2 for the HGA-S group. In the HGA-M group, the lower incisors
      were protruded, while in the HGA-S group, they were unaffected. The findings
      indicate that both modes of mandibular jumping resulted in skeletal and dental
      effects. The length of active treatment seemed to be decisive in maintaining the
      treatment effects; stepwise advancement had less dental effects.

PMID- 17556730
TI  - Expression of trace amine-associated receptors in the Grueneberg ganglion.
AB  - The Grueneberg ganglion (GG) in the vestibule of the anterior nasal cavity is
      considered as an olfactory subcompartment based on expression of the olfactory
      marker protein (OMP) and axonal projection to the olfactory bulb. Searching for
      olfactory receptors present in the GG, it has been observed recently that V2r83,
      a member of the V2R class of olfactory receptors, is expressed in numerous cells
      in the GG of mice. However, no other olfactory receptors have been found to be
      present in a considerable number of GG neurons so far. Here, we report that GG
      neurons express trace amine-associated receptors (TAARs) that have most recently
      been described as a novel class of olfactory receptors. It was observed that
      several TAAR subtypes are expressed by defined subpopulations of GG neurons
      distinct from the V2r83-positive cells. Analyzing the time course of TAAR
      expression during pre- and postnatal development revealed that TAARs are
      expressed by a substantial portion of GG neurons in late embryonic and neonatal
      stages, whereas in juveniles and adults, the number of TAAR-positive cells in the
      GG was significantly decreased.

PMID- 17556731
TI  - On language, education, and cochlear implants.

PMID- 17556733
TI  - Short stature in children: a practical approach for primary care providers.

PMID- 17556732
TI  - Neuropsychological correlates of vocabulary, reading, and working memory in deaf
      children with cochlear implants.
AB  - The performance of deaf children with cochlear implants was assessed using
      measures standardized on hearing children. To investigate nonverbal cognitive and
      sensorimotor processes associated with postimplant variability, five selected
      sensorimotor and visuospatial subtests from A Developmental Neuropsychological
      Assessment (NEPSY) were compared with standardized vocabulary, reading, and digit
      span measures. Participants were 26 deaf children, ages 6-14 years, who received
      a cochlear implant between ages 1 and 6 years; duration of implant use ranged
      from 3 to 11 years. Results indicated significant correlations between standard
      scores on the Design Copying subtest of the NEPSY and standard scores on
      vocabulary comprehension, reading, and digit span measures. The results
      contribute to our understanding of the benefits of cochlear implantation and
      cognitive processes that may support postimplant language and academic
      functioning.

PMID- 17556734
TI  - Sickle cell anemia: targeting the role of fetal hemoglobin in therapy.
AB  - Sickle cell anemia results from the single amino acid substitution of valine for
      glutamic acid in the beta-chain owing to a nucleotide defect that causes the
      production of abnormal beta-chains in hemoglobin S. Abnormal hemoglobin chains
      form polymers in the deoxygenated state, leading to the characteristic sickle
      cells. The polymerization of deoxygenated hemoglobin S accounts for the
      pathologic changes in sickle cell disease. The main-stay of therapy in sickle
      cell disease aims to reduce the amount of sickled hemoglobin present through the
      prevention of polymerization and reversal of this process. One way of
      discouraging polymerization is to increase the level of fetal hemoglobin, which
      because of its high oxygen affinity, does not participate in the polymerization
      process. Fetal hemoglobin production may be induced pharmacologically or by the
      use of gene therapy and genetic engineering techniques.

PMID- 17556735
TI  - The relationship between early respiratory viral infections and subsequent
      wheezing and asthma.

PMID- 17556736
TI  - Allergic rhinitis.

PMID- 17556737
TI  - Misperceptions about influenza vaccination among parents of healthy young
      children.
AB  - A survey was administered to 828 parents from metropolitan Denver, Colorado, and
      57% responded. Of the respondents, 47% thought their child was unlikely to
      contract influenza, 70% thought influenza vaccine could cause influenza, and 21%
      considered influenza vaccination unsafe for a 1-year-old child. The influenza
      immunization rate in children of surveyed parents was 71%. In multivariate
      analyses, the perception that influenza vaccination was the social norm was
      positively associated with immunization (odds ratio [OR], 1.32; 95% confidence
      interval [CI], 1.03-1.69), and anticipating immunization barriers was negatively
      associated with immunization (OR, 0.68; 95% CI, 0.49-0.95). Parents of young
      children hold a number of misperceptions about influenza disease and vaccination.
      Despite this, high immunization rates are achievable in this population.

PMID- 17556738
TI  - Familiarity of pediatricians with different commercially available neonatal and
      infant formulas.
AB  - To assess the familiarity of pediatricians with commercially available formulas
      and their use for cow's milk protein allergy and colic, a list of formulas was
      generated by visiting several grocery stores. Pediatricians were ask to indicate
      their familiarity with these and other "specialized" formulas with regard to
      protein and carbohydrate sources, energy content, hypoallergenicity, and
      indication for infant colic. The participants answered an average of 46% of the
      questions correctly. Respondents were very familiar with 27% of the formulas, and
      unfamiliar with 35%. The highest score was 70%, and 10% of the responders
      correctly answered 65% or more of the questions. Fifty-one percent correctly
      identified the protein source of the formulas; 32% correctly identified the
      carbohydrate source. The energy content of the formulas was correctly identified
      by 54%. These data suggest that pediatricians have a poor understanding of the
      content and appropriate use of neonatal and infant formulas.

PMID- 17556739
TI  - Behavioral health practices in the midst of black box warnings and mental health
      reform.
AB  - A standard guide was readministered to 42 primary care pediatricians after
      community interventions to assess changes in their behavioral health practices.
      Among the outcome findings: increased screening of young children (6 months to 5
      years); attention deficit hyperactivity disorder continued to be the most
      frequent diagnosis, with a high level of diagnostic comfort and use of
      stimulants; decreased comfort in the diagnosis and treatment of depression, with
      a significant decline in use of selective serotonin reuptake inhibitors; nearly
      all continued to offer nonmedication, behavioral health treatment; and a
      significant increase in use of social workers for community referrals. Structured
      interventions had limited influence on the process of change. Black box warnings
      exerted a powerful effect on prescribing practices. Systemic changes involving
      financial incentives, increased access to mental health providers, practice
      guidelines, and technology for continuing education may offer possibilities for
      changing practice patterns.

PMID- 17556740
TI  - Parent-reported physician diagnosis is an important factor in asthma management:
      an elementary school survey.
AB  - Parent surveys seem to provide sufficient information for asthma case selection.
      In this study, elementary school children were identified for an asthma education
      program through a screening questionnaire, followed by a comprehensive family
      survey. The data were analyzed by groups according to those with parent-reported
      physician diagnosis or no physician diagnosis. Those with an asthma diagnosis had
      less nighttime symptoms, less family stress, and more asthma follow-up visits,
      and were prescribed appropriate medications and peak flow meters more often than
      those students without a physician diagnosis of asthma. A physician commitment to
      or recognition of an asthma diagnosis is an important factor in subsequent asthma
      care.

PMID- 17556741
TI  - Predicting pertussis in a pediatric emergency department population.
AB  - Cases of pertussis, a potentially life-threatening illness in infants younger
      than 6 months of age, are at a 40-year high. Children frequently present to
      emergency departments for initial evaluation. Quick recognition of the illness
      allows rapid triage, isolation, and prevention of nosocomial transmission. A
      retrospective, case-control chart review was conducted of pediatric emergency
      department patients (0 to 18 years of age) presenting between January 1, 2003,
      and December 31, 2004. Analysis focused on the exploration of medical history and
      physical examination variables as predictors using laboratory verification of the
      presence of pertussis as a binary outcome variable. Infants younger than 2 months
      who have a cough or choking associated with cyanosis, as well as a cough and
      rhonchi on physical examination, have a high likelihood of pertussis and should
      be identified in triage, isolated immediately, and tested for pertussis. This may
      lead to appropriate therapy for this population and decrease the transmission of
      pertussis to other patients and staff in the pediatric emergency department.

PMID- 17556742
TI  - Nonfasting low-density lipoprotein testing: utility for cholesterol screening in
      pediatric primary care.
AB  - This prospective study assessed the clinical application of a nonfasting low
      density lipoprotein cholesterol measure in a pediatric primary care population. A
      homogenous direct low-density lipoprotein cholesterol assay was tested in healthy
      children, aged 4 to 12 years, at risk for hyperlipidemia, as defined by American
      Academy of Pediatrics, and including patients with incomplete family histories.
      This nonfasting homogeneous assay was comparable to modified beta quantification,
      the gold standard reference method of measuring low-density lipoprotein
      cholesterol, and the current recommended screening method, total cholesterol.
      Results from the study suggest that this nonfasting assay can provide more direct
      low-density lipoprotein cholesterol measurements for healthy children, with
      improved clinical utility and greater overall patient convenience in testing for
      important cholesterol abnormalities.

PMID- 17556743
TI  - Resident continuity clinic: a modest proposal.
AB  - Resident continuity clinics are an integral and mandated component of the
      pediatric core curriculum. Hospital-based and community-based settings have been
      traditionally used, with varied success. This article proposes the use and
      testing of an additional site, the primary care clinic housed at the Children's
      Clinic for Rehabilitative Services. This site provides concomitant continuity,
      and community and advocacy experiences for children with complex chronic
      conditions. Further study of the educational efficiency of this site is
      warranted.

PMID- 17556744
TI  - Bra-band wound in an adolescent.

PMID- 17556745
TI  - Cutaneous vasculitis associated with Mycoplasma pneumoniae infection: case report
      and literature review.
AB  - Mycoplasma pneumoniae is an important bacterial agent that causes pneumonia in
      pediatric patients; it can also affect other organs or systems. Extrapulmonary
      manifestations include neurological, cardiac, hematologic, renal,
      gastrointestinal, osteoarticular, cutaneous, and ocular involvement. This report
      presents a 7-year-old male affected with cutaneous and retinal vasculitis due to
      M pneumoniae infection without pulmonary detection. The available literature on
      cutaneous vasculitis and M pneumoniae infection is also reviewed.

PMID- 17556746
TI  - Asthma and hyperglycemia. Patient report.

PMID- 17556747
TI  - A neonate with persistent twitching. Patient report.

PMID- 17556748
TI  - Anemia. Patient report.

PMID- 17556749
TI  - Aggressive sibling.

PMID- 17556750
TI  - On the centrality and significance of stimulus-encoding deficit in schizophrenia.
AB  - Increased latency of stimulus encoding is presented as a central deficit in
      schizophrenia cognition. Encoding, here, entails the internal representation of
      presenting stimuli in a format facilitating their implementation in other
      cognitive processes, such as those taking place in working memory. Historical
      roots of suspected encoding debility in schizophrenia briefly are reviewed, and
      its singular empirical robustness is described. More recently, this deficit has
      been subjected to stochastic mathematical modeling, resulting in its
      decomposition into discrete cognitive functions. A nonmathematical exposition of
      this account is provided, and substantial behavioral study support is
      illustrated. Implications for clinical assessment of individuals and of treatment
      regimens, with respect to encoding-related cognitive efficiency, are noted.
      Finally, because stochastic dynamic trajectories of process duration are modeled,
      times of measurement interest, complementing neuroanatomical regions of interest,
      become available for enhanced temporal navigation of event-related fMRI. Results
      from recent implementations of such process-defined events are described.

PMID- 17556751
TI  - DSM-V research agenda: substance abuse/psychosis comorbidity.
AB  - For diagnosis of patients with comorbid psychotic symptoms and substance use
      disorders (SUDs), Diagnostic and Statistical Manual of Mental Disorders, Fourth
      Edition, makes clear distinctions between independent psychotic disorders (eg,
      bipolar disorder, schizophrenia) and substance-induced syndromes (eg, delirium,
      dementias). Most substance-induced psychotic symptoms are considered to be short
      lived and to resolve with sustained abstinence along with other symptoms of
      substance intoxication and withdrawal. These guidelines are challenged by
      practical difficulties in distinguishing between substance-induced and
      independent psychoses and by mounting evidence that marijuana use may be a
      contributing cause of schizophrenia. To inform the diagnostic distinction between
      substance-induced vs independent psychotic symptoms, 2 kinds of information could
      be sought from longitudinal research: (a) identification of early markers that
      clearly differentiate the 2 conditions and (b) more precise information about
      duration of psychotic symptoms induced by different substances. Evidence of this
      type could emerge from reanalysis of existing data from large-scale longitudinal
      studies of community samples. To inform possible nosological changes related to
      the possible schizophrenia-inducing role of marijuana (eg, designating a
      "cannabis-induced" subtype), a wide range of research evidence will be needed to
      clarify the relationship between effects of cannabis and schizophrenia symptoms.
      Ultimately, the ideal psychiatric nomenclature will define syndromes on the basis
      of established etiology and/or pathophysiology. Given the strong association
      between SUDs and psychotic disorders, research on the neurobiology of psychotic
      disorders could fruitfully include subjects with comorbid SUDs to shed light on
      shared etiology and pathophysiology.

PMID- 17556752
TI  - Spontaneous low-frequency fluctuations in the BOLD signal in schizophrenic
      patients: anomalies in the default network.
AB  - Spontaneous low-frequency fluctuations in the blood oxygen level-dependent (BOLD)
      functional magnetic resonance imaging (MRI) signal have been shown to reflect
      neural synchrony between brain regions. A "default network" of spontaneous low
      frequency fluctuations has been described in healthy volunteers during stimulus
      independent thought. Negatively correlated with this network are regions
      activated during attention-demanding tasks. Both these networks involve brain
      regions and functions that have been linked with schizophrenia in previous
      research. The present study examined spontaneous slow fluctuations in the BOLD
      signal at rest, as measured by correlation with low-frequency oscillations in the
      posterior cingulate, in 17 schizophrenic patients, and 17 comparable healthy
      volunteers. Healthy volunteers demonstrated correlation between spontaneous low
      frequency fluctuations of the BOLD signal in the posterior cingulate and
      fluctuations in the lateral parietal, medial prefrontal, and cerebellar regions,
      similar to previous reports. Schizophrenic patients had significantly less
      correlation between spontaneous slow activity in the posterior cingulate and that
      in the lateral parietal, medial prefrontal, and cerebellar regions. Connectivity
      of the posterior cingulate was found to vary with both positive and negative
      symptoms in schizophrenic patients. Because these data suggest significant
      abnormalities in resting-state neural networks in schizophrenia, further
      investigations of spontaneous slow fluctuations of the BOLD signal seem warranted
      in this population.

PMID- 17556753
TI  - Modelling the geometric features and investigating electrical properties of
      dendrites in a fish thalamic neuron.
AB  - A certain pacific fish has a thalamic nerve cell with a unique dendritic
      geometry. Instead of the cell having a branching dendritic structure, the large
      cell of the corpus glomerulosum has, generally, a single dendritic stalk with a
      large bulbous tip. We formulate a cable-theory model that incorporates the
      geometry, and then, we solve the problem for a single, localized synaptic current
      source at the bulb. From the solution representation, we numerically examine the
      characteristics of the postsynaptic potential due to the presence of the bulbous
      tip.

PMID- 17556754
TI  - Neutral sphingomyelinase-induced ceramide triggers germinal vesicle breakdown and
      oxidant-dependent apoptosis in Xenopus laevis oocytes.
AB  - Ceramide regulates many cellular processes, including cell growth,
      differentiation, and apoptosis. Although the effects of exogenous bacterial
      neutral sphingomyelinase (SMase) in Xenopus laevis oocytes have been
      investigated, its microinjection into oocytes has not been reported previously.
      Thus, we compared the incubation versus microinjection of the neutral Bacillus
      cereus sphingomyelinase (bSMase) to examine whether the topology of ceramide
      generation determines its effects on the fate of oocytes. In agreement with
      previous findings, incubation of mature stage VI oocytes with bSMase increased
      ceramide levels in oocyte extracts over time, causing the germinal vesicle
      breakdown indicative of maturation, without evidence of cytotoxicity. In
      contrast, bSMase microinjection, which increased ceramide levels in a time- and
      dose-dependent manner, resulted in oocyte apoptosis characterized by reactive
      oxygen species (ROS) generation, reduced glutathione (GSH) depletion in cytosol
      and mitochondria, release of cytochrome c and Smac/Diablo from mitochondria, and
      caspase-3 activation. Microinjection of acidic SMase from human placenta
      recapitulated the apoptotic effects of bSMase microinjection. Preincubation of
      oocytes with GSH-ethyl ester before bSMase microinjection prevented ROS
      generation and mitochondrial downstream events, thus protecting oocytes from
      bSMase-induced death. These findings show a divergent action of bSMase-induced
      ceramide on oocyte maturation or apoptosis depending on the intracellular site
      where ceramide is generated.

PMID- 17556755
TI  - Mutational reversions during adaptive protein evolution.
AB  - Adaptation is often regarded as the sequential fixation of individually,
      intrinsically beneficial mutations. Contrary to this expectation, we find a
      surprisingly large number of evolutionary trajectories on which natural selection
      first favors a mutation, then favors its removal, and later still favors its
      ultimate restoration during the course of antibiotic resistance evolution. The
      existence of reversion trajectories implies that natural selection may not follow
      the most parsimonious path separating two alleles, even during adaptation.
      Altogether, this discovery highlights the unusual and potentially circuitous
      routes natural selection can follow during adaptation.

PMID- 17556756
TI  - PIF-like transposons are common in drosophila and have been repeatedly
      domesticated to generate new host genes.
AB  - The P instability factor or PIF superfamily of DNA transposons constitutes an
      important group of transposable elements (TEs) in plants, but it is still poorly
      characterized in metazoans. Taking advantage of the availability of draft genome
      sequences for twelve Drosophila species, we discovered 4 different lineages of
      Drosophila PIF-like transposons, named DPLT1-4. These lineages have experienced a
      complex evolutionary history during the Drosophila radiation, involving
      differential amplification and retention among species and probable events of
      horizontal transmission. Like previously described plant and animal PIF
      transposons, full-length DPLTs encode a putative transposase as well as a second
      predicted protein containing a Myb/SANT domain. In DPLTs, this domain is most
      closely related to the MADF DNA-binding domain found in several Drosophila
      transcription factors. In addition, we identified 7 distinct genes distributed
      across the Drosophila genus that encode proteins related to PIF transposases, but
      lack the hallmarks of transposons. Instead, these sequences show features of
      functional genes, such as an intact coding region evolving under purifying
      selection, the presence of orthologs in at least 2 Drosophila species, and the
      conservation of intron/exon structure across orthologs. We also provide evidence
      that most of these genes are transcribed and that some are developmentally
      regulated. Together the data indicate that these genes derived from PIF
      transposons that have been "domesticated" to serve cellular functions. In one
      instance the recruitment of the transposase gene was accompanied by the co
      recruitment of the adjacent second PIF gene, which raises the hypothesis that
      both proteins now function in the same pathway. The second PIF gene has retained
      the capacity to encode a protein with an intact MADF domain, suggesting that it
      may function as a transcription factor. We conclude that PIF transposons are
      common in the Drosophila lineage and have been a recurrent source of new genes
      during Drosophila evolution.

PMID- 17556757
TI  - The impact of fossils and taxon sampling on ancient molecular dating analyses.
AB  - The number and complexity of molecular dating studies has increased over the past
      decade. Along with a broadening acceptance of their utility has come significant
      controversy over the methods and models that are appropriate, as well as the
      accuracy of the estimates yielded by molecular clock analyses. Radically
      different age estimates have been published for the same divergences from
      analyses of different datasets with different fossil constraints obtained with
      different methods, and the underlying explanation for these differences is often
      unclear. Here we utilize two previously published datasets to examine the effect
      of fossil calibrations and taxon sampling on the age estimates for two deep
      eukaryote divergences in an attempt to discern the relative impact of these
      factors. Penalized likelihood, non-parametric rate smoothing, and Bayesian
      methods were utilized to generate age estimates for the origin of the Metazoa
      from a 7-gene dataset and for the divergence of Eukaryotes from a 129-gene
      dataset. From these analyses, it is clear that the fossil calibrations chosen and
      the method for applying constraints to these nodes have a large impact on age
      estimates, while the degree of taxon sampling within a dataset is less important
      in terms of the resulting age estimates. Concerns and recommendations for
      addressing these two factors when initiating a dating analysis are discussed.

PMID- 17556758
TI  - The molecular evolution of avian ultraviolet- and violet-sensitive visual
      pigments.
AB  - The shortwave-sensitive SWS1 class of vertebrate visual pigments range in
      lambda(max) from the violet (385-445 nm) to the ultraviolet (UV) (365-355 nm),
      with UV-sensitivity almost certainly ancestral. In birds, however, the UV
      sensitive pigments present in a number of species have evolved secondarily from
      an avian violet-sensitive (VS) pigment. All avian VS pigments expressed in vitro
      to date encode Ser86 whereas Phe86 is present in all non-avian ultraviolet
      sensitive (UVS) pigments. In this paper, we show by site directed mutagenesis of
      avian VS pigments that Ser86 is required in an avian VS pigment to maintain
      violet-sensitivity and therefore underlies the evolution of avian VS pigments.
      The major mechanism for the evolution of avian UVS pigments from an ancestral
      avian VS pigment is undoubtedly a Ser90Cys substitution. However, Phe86, as found
      in the Blue-crowned trogon, will also short-wave shift the pigeon VS pigment into
      the UV whereas Ala86 and Cys86 which are also found in natural avian pigments do
      not generate short-wave shifts when substituted into the pigeon pigment. From
      available data on avian SWS1 pigments, it would appear that UVS pigments have
      evolved on at least 5 separate occasions and utilize 2 different mechanisms for
      the short-wave shift.

PMID- 17556759
TI  - Functional characterization and evolutionary history of two aryl hydrocarbon
      receptor isoforms (AhR1 and AhR2) from avian species.
AB  - Dioxins including 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induce various toxic
      effects through the aryl hydrocarbon receptor (AhR) signaling pathway. Here, we
      investigated the structural and functional characteristics and molecular
      evolution of multiple AhRs in black-footed albatross (Phoebastria nigripes) and
      common cormorant (Phalacrocorax carbo). We report the complementary DNA sequences
      of two distinct AhRs, designated AhR1 and AhR2, from these species as well as the
      identification of an AhR2-like gene sequence from the chicken genome database.
      Phylogenetic analysis reveals that avian AhR1 and AhR2 are orthologous to
      mammalian AhR1 and fish AhR2, respectively, supporting the hypothesis that an
      ancestral AhR gene underwent a tandem duplication prior to the divergence of fish
      and tetrapod lineages. In vitro-expressed AhR1 and AhR2 isoforms from both
      albatross and cormorant exhibited specific binding to [3H]TCDD, as assessed by
      velocity sedimentation. An in vitro reporter gene transactivation assay revealed
      that both AhR1 and AhR2 are transcriptionally active, but AhR2 appears to have
      reduced transcriptional efficacy. Hepatic messenger RNA expression level of
      cormorant AhR1 was greater than that of AhR2. Together, these results suggest
      that AhR1 is the dominant form of avian AhRs, in contrast to fish, in which AhR2
      is the major form. Comparative analysis of AhR diversity and gene synteny among
      chicken, zebrafish, and human suggests that additional, independent AhR
      duplications have occurred in the fish and tetrapod lineages following the
      initial tandem duplication on the ancestral chromosome. The identification and
      characterization of avian AhR1 and AhR2 provide new insight into the evolution of
      AhR structure and function in vertebrates.

PMID- 17556760
TI  - Invited commentary: identifying women with hypertension during pregnancy--is high
      specificity sufficient?
AB  - Hypertensive complications of pregnancy contribute to the burden of maternal
      morbidity and subsequently have an impact on neonatal morbidity and mortality.
      Although codes from the International Classification of Diseases should delineate
      the specific subtypes of pregnancy-related hypertension, how diagnoses are
      applied and how these codes are used in clinical settings are largely unknown.
      This commentary discusses the implications of using administrative codes to
      identify women with preeclampsia syndromes, especially when used to define
      outcomes or exposures for etiologic research.

PMID- 17556761
TI  - Validity of preeclampsia-related diagnoses recorded in a national hospital
      registry and in a postpartum interview of the women.
AB  - In a population-based sample, the authors examined the validity of preeclampsia
      and related diagnoses recorded in a mandatory Danish national hospital discharge
      registry and in a standardized telephone interview of women who gave birth
      between 1998 and 2002. Using a "gold standard" for preeclampsia defined in
      accordance with the guidelines from the American College of Obstetricians and
      Gynecologists, the authors reviewed hospital charts of 3,039 women and found that
      61 of 88 preeclampsia cases (69.3%) and 24 of 55 cases of serious subtypes of
      preeclampsia (43.6%) were recorded as such by the registry. A total of 21 of
      2,951 women without preeclampsia (0.71%) had a preeclampsia diagnosis in the
      registry. All registrations of serious subtypes of preeclampsia reflected true
      cases. The positive predictive value of a preeclampsia diagnosis in the registry
      was 74.4%. Including interview data reduced the sample size to 2,307 women. In
      this sample, of 62 women with preeclampsia, 45 (72.6%) reported in the interview
      to have had preeclampsia. Of 2,245 women with no preeclampsia, 31 (1.4%) reported
      to have had preeclampsia. The positive predictive value of the women's own report
      on preeclampsia was 59.2%. The authors conclude, for the purpose of etiologic
      studies, that the registry had acceptable validity, whereas the usefulness of
      self-reported information may be limited.

PMID- 17556762
TI  - Cohort differences in self-rated health: evidence from a three-decade, community
      based, longitudinal study of women.
AB  - Despite the fact that life expectancy has nearly doubled over the past century,
      the US public has become increasingly preoccupied with issues of health and
      illness. In this study, the authors investigated cohort differences in self-rated
      health between women born in 1935-1944 (preboomers) and women born in 1945-1954
      (baby boomers). A randomly selected, community-based sample of 618 mothers, 314
      preboomers, and 304 baby boomers was interviewed. Over three decades, self-rated
      health was assessed in 1975, 1983, 1985-1986, 1991-1994, and 2001-2004. An
      individual growth model showed a linear decline (-0.61 per year, p<0.001) in self
      rated health from mean ages 31-59 years combined, with a quadratic age effect (
      0.03, p<0.001). Baby boomers reported lower self-rated health (mean difference, 
      5.30; p<0.001) and more rapid decline per year (slope difference, -0.52; p<0.001)
      than did preboomers of overlapping ages; those differences remained after
      adjusting for demographics, socioeconomic variables, personality factors, health
      behaviors, chronic illness, and depression symptoms. Study findings have
      important implications with regard to the potential growing burden on the
      nation's health care system, suggesting that generational changes in health
      evaluations and expectations may continue to increase demand for medical care.

PMID- 17556763
TI  - Using risk-based sampling to enrich cohorts for endpoints, genes, and exposures.
AB  - Targeting the first-degree relatives of people with a particular complex disease
      can offer a powerful approach to building a risk-based cohort for prospective
      studies of etiologic factors. Such a cohort provides both a sizable increase in
      the rate of accrual of newly incident cases, enriching for risk factors that are
      known or even unknown, and a high level of motivation among participants. A
      nationwide study of breast cancer in the United States and Puerto Rico, the
      Sister Study, made up of women who are each the sister of a woman with breast
      cancer, exemplifies this approach. In this paper, the authors provide power
      calculations to aid in the design of such studies and quantify their benefits for
      detecting both genetic variants related to risk and interactive effects of
      genetic and environmental factors. While the risk-based cohort can have markedly
      increased prevalences of rare causative alleles, most of the power advantages for
      this design is due to the increased rate of accrual of newly incident cases
      rather than the increase in any one individual allele.

PMID- 17556764
TI  - Radio-frequency radiation exposure from AM radio transmitters and childhood
      leukemia and brain cancer.
AB  - Leukemia and brain cancer patients under age 15 years, along with controls with
      respiratory illnesses who were matched to cases on age, sex, and year of
      diagnosis (1993-1999), were selected from 14 South Korean hospitals using the
      South Korean Medical Insurance Data System. Diagnoses were confirmed through the
      South Korean National Cancer Registry. Residential addresses were obtained from
      medical records. A newly developed prediction program incorporating a geographic
      information system that was modified by the results of actual measurements was
      used to estimate radio-frequency radiation (RFR) exposure from 31 amplitude
      modulation (AM) radio transmitters with a power of 20 kW or more. A total of
      1,928 leukemia patients, 956 brain cancer patients, and 3,082 controls were
      analyzed. Cancer risks were estimated using conditional logistic regression
      adjusted for residential area, socioeconomic status, and community population
      density. The odds ratio for all types of leukemia was 2.15 (95% confidence
      interval (CI): 1.00, 4.67) among children who resided within 2 km of the nearest
      AM radio transmitter as compared with those resided more than 20 km from it. For
      total RFR exposure from all transmitters, odds ratios for lymphocytic leukemia
      were 1.39 (95% CI: 1.04, 1.86) and 1.59 (95% CI: 1.19, 2.11) for children in the
      second and third quartiles, respectively, versus the lowest quartile. Brain
      cancer and infantile cancer were not associated with AM RFR.

PMID- 17556765
TI  - Promoting physical activity participation among children and adolescents.
AB  - With global increases in the prevalence of overweight and obesity among children
      and adolescents, there has never been a more urgent need for effective physical
      activity programs. The aim of this narrative review is to summarize the evidence
      of the effectiveness of interventions that report physical activity outcomes in
      children aged 4-12 years and adolescents aged 13-19 years. A systematic search of
      electronic databases identified 76 interventions. Most interventions were
      delivered via the school setting (57 interventions), nine through the family
      setting, six via primary care, and four in community- or Internet-based settings.
      Children's physical activity interventions that were most effective in the school
      setting included some focus on physical education, activity breaks, and family
      strategies. Interventions delivered in the family setting were not highly
      effective, but many were pilot studies. The use of motivationally tailored
      strategies and program delivery in the primary care setting showed promise among
      adolescents. Many studies had methodological and reporting flaws (e.g., no
      baseline data, poor study design, physical activity measures of unknown
      reliability and validity, and poor reporting of sample size, response rates,
      attrition/retention, compliance, year of intervention, and duration of
      intervention). Publications reporting the results of evaluations of intervention
      studies should follow the Consolidated Standards of Reporting Trials guidelines
      or, for nonrandomized studies, should follow the Transparent Reporting of
      Evaluations with Nonrandomized Designs guidelines. Further evidence of the
      effectiveness of interventions promoting young people's physical activity in
      family and community settings is needed.

PMID- 17556766
TI  - A citrus abscission agent induces anoxia- and senescence-related gene expression
      in Arabidopsis.
AB  - The mechanisms of negative effects of 5-chloro-3-methyl-4-nitro-1H-pyrazole
      (CMNP), a pyrazole-derived plant growth regulator used as a citrus abscission
      agent, were explored in Arabidopsis by integrating transcriptomic, physiological,
      and ultrastructural analyses. CMNP promoted starch degradation and senescence
      related symptoms, such as chloroplast membrane disruption, electrolyte leakage,
      and decreased chlorophyll and protein content. Symptoms of plant decline were
      evident 12 h after CMNP treatment. Microarray analysis revealed that CMNP
      influenced genes associated with stress, including those related to anoxia,
      senescence, and detoxification. Sucrose treatment arrested CMNP-induced plant
      decline. The results demonstrate that the plant response to CMNP shares common
      elements with various stresses and senescence at physiological and molecular
      levels.

PMID- 17556767
TI  - The challenge of improving nitrogen use efficiency in crop plants: towards a more
      central role for genetic variability and quantitative genetics within integrated
      approaches.
AB  - In this review, recent developments and future prospects of obtaining a better
      understanding of the regulation of nitrogen use efficiency in the main crop
      species cultivated in the world are presented. In these crops, an increased
      knowledge of the regulatory mechanisms controlling plant nitrogen economy is
      vital for improving nitrogen use efficiency and for reducing excessive input of
      fertilizers, while maintaining an acceptable yield. Using plants grown under
      agronomic conditions at low and high nitrogen fertilization regimes, it is now
      possible to develop whole-plant physiological studies combined with gene,
      protein, and metabolite profiling to build up a comprehensive picture depicting
      the different steps of nitrogen uptake, assimilation, and recycling to the final
      deposition in the seed. A critical overview is provided on how understanding of
      the physiological and molecular controls of N assimilation under varying
      environmental conditions in crops has been improved through the use of combined
      approaches, mainly based on whole-plant physiology, quantitative genetics, and
      forward and reverse genetics approaches. Current knowledge and prospects for
      future agronomic development and application for breeding crops adapted to lower
      fertilizer input are explored, taking into account the world economic and
      environmental constraints in the next century.

PMID- 17556768
TI  - Decreased panicle-derived indole-3-acetic acid reduces gibberellin A1 level in
      the uppermost internode, causing panicle enclosure in male sterile rice Zhenshan
      97A.
AB  - Cytoplasmic male sterile (CMS) rice Zhenshan 97A (ZS97A) has been widely used in
      hybrid rice production in China. However, ZS97A suffers from serious panicle
      enclosure, which blocks normal pollination and greatly reduces seed production of
      hybrid rice. Little is known about the cause of panicle closure in ZS97A. In this
      study, it was found that the occurrence of cytoplasmic male sterility caused a
      deficiency of indole-3-acetic acid (IAA) in ZS97A panicles, and less IAA was
      provided to the uppermost internode (UI). Further, it was found that the
      decreased panicle-derived IAA caused a gibberellin A(1) (GA(1)) deficiency in the
      UI by the down-regulation of OsGA3ox2 transcript level. Reduced GA(1) level in
      the UI led to decreases of both cell number and cell elongation, resulting in a
      shortened UI. The shortened UI was unable to push the panicle out of the flag
      leaf sheath that remained normal, which resulted in panicle enclosure in ZS97A.
      These findings suggest that decreased panicle-derived IAA reduces the GA(1) level
      in the UI, causing panicle enclosure in CMS rice ZS97A.

PMID- 17556769
TI  - Specialist competencies in occupational medicine: appraisal of the peer-reviewed
      literature.
AB  - BACKGROUND: A re-assessment of competencies and therefore learning outcomes for
      higher specialist training in occupational medicine (OM) is being undertaken.
      Although peer-reviewed literature on the subject exists, it is limited and needs
      appraisal. AIMS: To search, and critically appraise the peer-reviewed literature
      on specialist competencies in OM. METHODS: Systematic search of a range of
      databases of peer-reviewed literature, followed by criterion based appraisal and
      categorization of the findings. RESULTS: Two hundred and thirty five papers were
      found of which only 20 were left after application of the grading and exclusion
      criteria. These addressed competencies from four perspectives: peer consensus,
      client, educational and legal. CONCLUSIONS: Limited evidence can be obtained from
      the peer-reviewed literature on specialist competencies in OM. However, it
      suggests the main paradigms for deriving these competencies as well as indicating
      gaps and the manner in which these might be filled.

PMID- 17556770
TI  - Developmental downregulation of excitatory GABAergic transmission in neocortical
      layer I via presynaptic adenosine A(1) receptors.
AB  - Layer I of the developing cortex contains a dense GABAergic fiber plexus. These
      fibers provide excitatory inputs to Cajal-Retzius (CR) cells, the early born
      neurons in layer I. CR cells possess an extensive axonal projection and form
      synaptic contacts with excitatory, presumably pyramidal, neurons before birth.
      Interestingly, activity of CR cells declines during the first postnatal week, but
      mechanism(s) underlying this phenomenon is not yet known. Here we recorded
      inhibitory postsynaptic currents (IPSCs) in CR cells at postnatal day (P) 1-2 and
      P5-7. Blockade of adenosine A(1) receptors (A(1)Rs) increased the amplitude of
      evoked IPSCs (eIPSCs) and decreased paired-pulse ratio at P5-7 but not at P1-2.
      A(1)R activation decreased the mean eIPSC amplitude at P5-7, but failed to affect
      eIPSCs at P1-2. Ecto-adenosine triphosphatase (ATPase) inhibition completely
      abolished the A(1)R-mediated effects suggesting that extracellular ATP is the
      main source of adenosine. Because A(1)R blockade did not affect the median
      miniature IPSC amplitude, our results demonstrate that adenosine reduces gamma
      aminiobutyric acid (GABA) release probability via presynaptic A(1)Rs at P5-7. As
      neuronal activity in layer I can depolarize pyramidal neurons influencing thereby
      glutamatergic synaptogenesis in the lower cortical layers, postnatal weakening of
      GABAergic transmission by adenosinergic system might reflect a developmental
      downregulation of this excitatory drive when glutamatergic synapses are formed.

PMID- 17556771
TI  - Large-scale gamma-band phase synchronization and selective attention.
AB  - Explaining the emergence of a coherent conscious percept and an intentional agent
      from the activity of distributed neurons is key to understanding how the brain
      produces higher cognitive processes. Gamma-band synchronization has been proposed
      to be a mechanism for the functional integration of neural populations that
      together form a transitory, large-scale, task- and/or percept-specific network.
      The operation of this mechanism in the context of attention orienting entails
      that cortical regions representing attended locations should show more gamma-band
      synchronization with other cortical areas than would those representing
      unattended locations. This increased synchronization should be apparent in the
      same time frame as that of the deployment of attention to a particular location.
      In order to observe this effect, we made electroencephalogram recordings while
      subjects attended to one side or the other of the visual field (which we
      confirmed by event-related potential analysis) and calculated phase-locking
      statistics between the signals recorded at relevant electrode pairs. We observed
      increased gamma-band phase synchronization between visual cortex contralateral to
      the attended location and other, widespread, cortical areas approximately 240-380
      ms after the directional cue was presented, confirming the prediction of a large
      scale gamma synchronous network oriented to the cued location.

PMID- 17556772
TI  - When brightness counts: the neuronal correlate of numerical-luminance
      interference.
AB  - Previous studies showed that the processing of numerical information and spatial
      information such as physical size causes a mutual interference. The neuronal
      correlate of such interference was suggested to be in the parietal lobe. However,
      a previous study showed that such interference does not occur between numerical
      information and nonspatial dimensions such as luminance level (Pinel P, Piazza M,
      Le Bihan D, Dehaene S. 2004. Distributed and overlapping cerebral representations
      of number, size, and luminance during comparative judgments. Neuron. 41:983-993).
      Here it is shown that numerical value and luminance level do cause a behavioral
      interference and that this interference modulates the activity in the parietal
      lobe. The current results support the idea that the parietal lobe might be
      equipped with neuronal substrates for magnitude processing even for nonspatial
      dimensions.

PMID- 17556773
TI  - Cross-cultural generalizability of the theory of planned behavior among young
      people in a physical activity context.
AB  - The present study tested the cross-cultural generalizability of the measurement
      and structural parameters of the theory of planned behavior (TPB) among youth in
      a physical activity context. Pupils from five cultural groups completed measures
      of attitudes, subjective norms, perceived behavioral control (PBC), and
      intentions for physical activity. Five weeks later, participants completed self
      report measures of physical activity behavior. Confirmatory factor analyses and
      multisample structural equation models revealed well-fitting models within each
      sample with minimal variations in the measurement parameters across cultures.
      There were a few significant cross-cultural differences in the structural
      relations among the TPB constructs. Attitudes predicted intentions in all samples
      (beta range = .300 to .550), whereas the effect of the subjective norms on
      intention was nonsignificant in all but the Hungarian sample (beta = .243).
      Conversely, the effect of PBC on intentions was significant (beta range = .302 to
      .573) in all but the Hungarian sample. Findings support the generalizability of
      the measures and pattern of effects for the TPB among young people in a physical
      activity context.

PMID- 17556774
TI  - The mediating role of intention and stages of change in physical activity among
      adults with physical disabilities: an integrative framework.
AB  - The study's purpose was to identify the mediating role of intention and the
      stages of change (SOC) in physical activity (PA) over a 6-month period using two
      models (theory of planned behavior [TPB] and TPB/SOC). Participants were 143
      adults with physical disabilities (70.68% response rate; M age = 46.03). The TPB
      constructs, SOC (time 1), and PA (time 2) were assessed using standardized self
      report questionnaires. Based on path analyses, attitude had the highest effect on
      intention and SOC followed by perceived behavioral control within both well-fit
      models. The variance in PA explained by the first (TPB) and second (TPB/SOC)
      models was 16% and 28% respectively. In the just identified model of TPB/SOC, the
      direct effect of SOC on physical activity remained strong (gamma(soc.pa) = .45)
      and SOC approached full mediation through attitude. Health promotion
      interventions need to include both intention and behavior elements (SOC)
      reinforcing increased PA value and barrier elimination.

PMID- 17556775
TI  - Effects of a motivational climate inntervention for coaches on young athletes'
      sport performance anxiety.
AB  - The mastery approach to coaching is a cognitive-behavioral intervention designed
      to promote a mastery-involving motivational climate, shown in previous research
      to be related to lower anxiety in athletes. We tested the effects of this
      intervention on motivational climate and on changes in male and female
      athletes'cognitive and somatic performance anxiety over the course of a
      basketball season. Hierarchical linear modeling analyses revealed that the
      athletes in the intervention condition perceived their coaches as being more
      mastery-involving on the Motivational Climate Scale for Youth Sports when
      compared to athletes in an untreated control condition. Relative to athletes who
      played for untrained coaches, those who played for the trained coaches exhibited
      decreases on all subscales of the Sport Anxiety Scale-2 and on total anxiety
      score from preseason to late season. Control group athletes reported increases in
      anxiety over the season. The intervention had equally positive effects on boys
      and girls teams.

PMID- 17556776
TI  - Effects of focus of attention on baseball batting performance in players of
      differing skill levels.
AB  - This study addressed the question, what should baseball players focus their
      attention on while batting? Less-skilled and highly skilled (college) baseball
      players participated in four dual-task conditions in a baseball batting
      simulation: two that directed attention to skill execution (skill/internal
      [movement of the hands] and skill/external [movement of the bat]) and two that
      directed attention to the environment (environmental/irrelevant [auditory tones]
      and environmental/external [the ball leaving the bat]). Batting performance for
      highly skilled players was best in the environmental/external condition and worst
      in the skill/internal condition. Performance of less-skilled batters was
      significantly better in the two skill conditions than in either of the two
      environmental conditions. We conclude that the optimal focus of attention for
      highly skilled batters is one that does not disrupt proceduralized knowledge and
      permits attention to the perceptual effect of the action, whereas the optimal
      focus of attention for less-skilled batters is one that allows attention to the
      step-by-step execution of the swing.

PMID- 17556777
TI  - Preservation of visual attention in older expert orienteers at rest and under
      physical effort.
AB  - This study investigated the visual attention of older expert orienteers and older
      adults not practicing activities with high attentional and psychomotor demands,
      and considered whether prolonged practice of orienteering may counteract the age
      related deterioration of visual attentional performance both at rest and under
      acute exercise. In two discriminative reaction time experiments, performed both
      at rest and under submaximal physical workload, visual attention was cued by
      means of spatial cues of different sizes followed, at different stimulus-onset
      asynchronies, by compound stimuli with local and global target features.
      Orienteers, as compared to nonathletes, showed a faster reaction speed and a
      complex pattern of attentional differences depending on the time constraints of
      the attentional task, the demands on endogenous attentional control, and the
      presence or absence of a concomitant effortful motor task. Results suggest that
      older expert orienteers have developed attentional skills that outweigh, at least
      at rest, the age-related deficits of visual attentional focusing.

PMID- 17556778
TI  - Longitudinal patterns of stability and change in coping across three
      competitions: a latent class growth analysis.
AB  - An unresolved issue in the coping literature concerns the traitlike versus
      statelike nature of coping utilization. The aim of this study was to illustrate
      the benefits of moving beyond the sole reliance on mean-level and rank-order
      analyses in order to identify heterogeneous patterns of longitudinal stability
      and change in coping utilization. More specifically, this study hypothesized that
      not all athletes would change their coping across competitions, nor do all
      "changers" change in a similar manner. Male soccer players (N = 107) completed a
      self-reported coping measure after three competitions held over a 6-month period.
      Results of latent class growth modeling showed three distinct trajectories for
      each coping dimension (i.e., task, distraction, and disengagement coping), not
      only indicating linear or quadratic change, but also stability in longitudinal
      coping utilization. These results highlight the need to account for the
      multinomial heterogeneity in longitudinal coping utilization and to identify the
      correlates associated with distinct trajectories of change and stability of
      coping across competitions.

PMID- 17556779
TI  - Benefits of a physical activity intervention for men with prostate cancer.
AB  - The purpose of the current study was to examine the viability of conducting a
      theory-based physical activity (PA) intervention on men with prostate cancer, and
      the impact of PA on quality of life (QOL). Participants were 31 men, average age
      of 67 years, with localized or metastatic prostate cancer undergoing androgen
      deprivation therapy (ADT). Global QOL, fatigue, and PA measures were conducted at
      baseline and following the 12-week intervention. An additional follow-up testing
      was conducted 4 months following the intervention (n = 18). Both moderate and
      strenuous bouts of exercise, as well as functional capacity, increased
      significantly from pre- to posttest. Both fatigue severity and resting heart rate
      decreased significantly at posttest. A trend toward improved global QOL was also
      noted. It was concluded that a 12-week home-based PA intervention may provide
      health and QOL benefits for prostate cancer patients undergoing ADT.
      Practitioners are encouraged to promote PA for prostate cancer survivors.

PMID- 17556780
TI  - Affective and self-efficacy responses to acute aerobic exercise in sedentary
      older and younger adults.
AB  - This study examined the psychological responses to an acute bout of aerobic
      exercise in sedentary older and younger adults. Eighteen young (mean age 24
      years) and 15 older adults (mean age 64 years) completed a 20-min bout of
      stationary cycling at 65% of VO2peak. Affective responses were assessed before,
      during, and immediately after exercise. Participants'exercise self-efficacy
      beliefs were assessed before and immediately after exercise. Both groups reported
      reduced pleasant feeling states and self-efficacy and increased physical
      exhaustion in response to acute exercise. Older adults also demonstrated a
      significant decrease in revitalization during and after cycling. Correlation
      analyses revealed that self-efficacy was related to feelings of fatigue during
      exercise and postexercise feelings of energy and fatigue. Both groups reported
      negative shifts in affect and self-efficacy during and 5 min after cycling.Acute
      affective and self-efficacy responses might influence one's motivation to adopt
      and maintain regular physical activity. The relationship between these acute
      responses and physical activity behavior across the life span warrants future
      inquiry.

PMID- 17556781
TI  - Tai Chi-based exercise for older adults with Parkinson's disease: a pilot-program
      evaluation.
AB  - The primary objective of this study was to provide preliminary evaluation of the
      feasibility, safety, and efficacy of a newly developed Tai Chi-based exercise
      program for older adults with Parkinson's disease (PD). Using a one-group pretest
      posttest design, 17 community-dwelling adults (mean age 71.51 years) with mild to
      moderate idiopathic PD (Stage I, II, or III on the Hoehn and Yahr scale) and
      stable medication use completed a 5-day, 90-min/day Tai Chi exercise-evaluation
      program. Outcome measures included face-to-face exit interviews on
      appropriateness and safety and physical performance (i.e., 50-ft speed walk, up
      and-go, functional reach). At the end of this brief intervention, exercise
      adherence was 100% and the program was shown to be safe. Exit interviews
      indicated that the program was well received by all participants with respect to
      program appropriateness, participant satisfaction and enjoyment, and intentions
      to continue. Furthermore, a significant pretest-to-posttest change was observed
      at the end of the 5-day program in all three physical-performance measures (p <
      .05). The results of this pilot evaluation suggest that Tai Chi is an appropriate
      physical activity for older adults with PD and might also be useful as a
      therapeutic exercise modality for improving and maintaining physical function.
      These preliminary findings warrant further investigation.

PMID- 17556782
TI  - Reducing attrition in physical activity programs for older adults.
AB  - This study investigated attrition in a 6-month physical activity intervention for
      older adults. The program was based on the social-cognitive theory incorporating
      self-efficacy factors. Two hundred forty-eight insufficiently active 65- to 74
      year-olds were recruited from the Australian federal electoral roll. The
      intervention comprised walking and strength and flexibility exercises and was
      conducted in 30 local neighborhoods where the participants resided.
      Characteristics of individuals lost to attrition (n = 86, 35%) were compared with
      those of program completers (n = 162, 65%). Logistic-regression analysis showed
      that those lost to attrition came from areas of lower socioeconomic status, were
      overweight and less physically active, and had lower walking self-efficacy scores
      and higher loneliness scores. The results suggest that early assessment of these
      characteristics should be undertaken to identify individuals at risk of
      attrition, to improve retention, and to avoid potential bias.

PMID- 17556783
TI  - A case study of physical activity among older adults in rural Newfoundland,
      Canada.
AB  - The purpose of this study was to assess rural older adults' perceptions of
      leisure-time physical activity and examine these perceptions from a historical
      perspective. Semistructured interviews were conducted with 10 inhabitants (mean
      age 82 years) of Fogo Island, Newfoundland and Labrador, Canada. Interviews were
      transcribed verbatim and subjected to inductive analysis. Member-checking
      interviews were conducted with 5 participants. Findings indicated that beginning
      in childhood, participants were socialized into a subculture of work activity. As
      a result of these historical and social forces, leisure-time physical activity
      did not form part of the participants' lives after retirement. Strategies for
      successful aging involved keeping busy, but this "busyness" did not include
      leisure-time physical activity. Results demonstrated the importance of developing
      a broader understanding of how past and present-day contexts can influence
      participation in leisure-time physical activity.

PMID- 17556784
TI  - Reliability and validity of responses to submaximal all-extremity semirecumbent
      exercise in older adults.
AB  - Although popular in clinical settings, little is known about the utility of all
      extremity semirecumbent exercise machines for research. Twenty-one community
      dwelling older adults performed two exercise trials (three 4-min stages at
      increasing workloads) to evaluate the reliability and validity of exercise
      responses to submaximal all-extremity semirecumbent exercise (BioStep). Exercise
      responses were measured directly (Cosmed K4b2) and indirectly through software on
      the BioStep. Test-retest reliability (ICC2,1) was moderate to high across all
      three stages for directly measured METs (.92, .87, and .88) and HR (.91, .83, and
      .86). Concurrent criterion validity between the K4b2 and BioStep MET values was
      moderate to very good across the three stages on both Day 1 (r = .86, .71, and
      .83) and Day 2 (r = .73, .87, and .72). All-extremity semirecumbent submaximal
      exercise elicited reliable and valid responses in our sample of older adults and
      thus can be considered a viable exercise mode.

PMID- 17556785
TI  - Combination training and resistance training as effective interventions to
      improve functioning in elders.
AB  - The purpose of the study was to determine whether resistance training (RT) or a
      combination of resistance and aerobic training (CT) resulted in the most
      improvement in measures of functional ability in functionally limited elders.
      Elderly adults who exhibited some limits in functional ability were randomly
      assigned to either a CT, RT, or control (C) group. Both RT and CT exercised three
      times per week for 16 weeks. At Weeks 0 and 17, participants completed six
      measures of strength and six functional tests. A 3 (group) x 3 (time) ANOVA with
      repeated measures on the time factor was used to analyze the results. CT and RT
      scored significantly better than C at Week 17 for biceps curl, elbow extension,
      chair stand, and time up the stairs. These findings demonstrate that RT and CT
      are both effective at increasing measures of strength and functional ability in
      elderly adults who begin exercise with functional limitations.

PMID- 17556786
TI  - Older adults' exercise behavior: roles of selected constructs of social-cognitive
      theory.
AB  - Exercise is consistently related to physical and psychological health benefits in
      older adults. Bandura's social-cognitive theory (SCT) is one theoretical
      perspective on understanding and predicting exercise behavior. Thus, the authors
      examined whether three SCT variables-self-efficacy, self-regulation, and outcome
      expectancy value-predicted older adults' (N = 98) exercise behavior. Bivariate
      analyses revealed that regular exercise was associated with being male, White,
      and married; having higher income, education, and self-efficacy; using self
      regulation skills; and having favorable outcome-expectancy values (p < .05). In a
      simultaneous multivariate model, however, self-regulation (p = .0097) was the
      only variable independently associated with regular exercise. Thus, exercise
      interventions targeting older adults should include components aimed at
      increasing the use of self-regulation strategies.

PMID- 17556787
TI  - Comparison style, physical self-perceptions, and fitness among older women.
AB  - This study examined the relationships between older women's comparison styles,
      physical self-perceptions, and functional fitness. Participants were community
      dwelling women (N = 102, age 65-99) living in the mid-Atlantic region of the
      United States. Individuals were categorized as relying primarily on social
      comparisons, temporal comparisons, or a combination of both styles. Also of
      interest was whether individuals evaluated themselves positively or negatively
      when making comparisons. Participants who evaluated themselves positively as
      compared with others were found to have higher levels of physical self
      perception. Analyses revealed that women who relied primarily on temporal
      comparisons had higher self-perceptions of their functional ability than those
      who relied on a combination of comparison styles. An avoidance of both temporal
      and social comparisons was also related to higher levels of physical self
      perception.

PMID- 17556788
TI  - Statin's cost-effectiveness: a Canadian analysis of commonly prescribed generic
      and brand name statins.
AB  - BACKGROUND: Generic statins may be considered as a compelling treatment option
      for managing dyslipidemia, due to their reduced cost, compared to their brand
      name equivalent. However, further assessment is needed to determine whether using
      a particular generic statin is more cost-effective relative to other brand-name
      statins. OBJECTIVE: The purpose of this study is to compare the cost
      effectiveness of the most commonly prescribed statins in Canada with respect to
      1) lowering low-density lipoprotein cholesterol level (LDL-C) and 2) achieving
      National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III)
      LDL-C goal. METHODS: The study was conducted from the perspective of Canadian
      payers over a 1-year time horizon. Clinical data were obtained from the STELLAR
      trial (n=2268) in which patients received fixed doses of rosuvastatin,
      atorvastatin, simvastatin and pravastatin. Brand and generic drug costs were
      based on wholesale acquisition costs. Relative cost-effectiveness was assessed
      using the net monetary benefit approach (NMB), which allows probabilistic cost
      effectiveness comparison of the various treatment options over a wide range of
      willingness-to-pay (WTP) values for a unit of clinical effect. RESULTS:
      Rosuvastatin 10mg was the most cost-effective statin over the largest range of
      WTP values. Pravastatin 10mg was cost-effective when the clinical outcomes had
      little or no monetary value. Rosuvastatin 20 mg was more cost-effective at the
      highest end of the WTP spectrum. CONCLUSION: The result of this analysis provides
      evidence that prescribing generic statins in Canada does not necessarily
      translate into the most cost-effective option for treating dyslipidemia;
      especially as the monetary value of 1% decrease in LDL-C or patients achieving
      NCEP ATP III target increases.

PMID- 17556790
TI  - No association found between patients receiving isotretinoin for acne and the
      development of depression in a Canadian prospective cohort.
AB  - BACKGROUND: There has been concern that the use of isotretinoin to treat acne may
      lead to depression. To date, research has not conclusively determined if this
      concern is warranted when contemplating the use of isotretinoin. OBJECTIVE: This
      study investigated the impact of isotretinoin use for patients with acne on mood
      status. The hypothesis was that an association exists between the use of
      isotretinoin and the development of depression, aside from acne severity.
      METHODS: We studied the relationship between isotretinoin and depression using a
      prospective, controlled, cohort design. The study was conducted in a community
      dermatology clinic. The exposed cohort consisted of consenting patients who were
      initiating isotretinoin treatment for acne. Patients were either treated with
      isotretinoin (Acutanei) therapy (study group) (N=100) or by oral (N=41) or
      topical acne therapy (control group) (N=59). The Center for Epidemiologic Studies
      Depression scale and the Zung Depression Status Inventory were used to assess
      depression both at baseline and after 2 months of prescribed use of isotretinoin
      or a control medication (topical or oral antibiotics). RESULTS: There was no
      correlation between isotretinoin use and the development of depression, based on
      either the Centre for Epidemiologic Studies Depression scale (Fisheras exact
      test, P=0.497) or Zung Depression Status Inventory (ANOVA; F=1.4, P=0.2).
      CONCLUSION: Isotretinoin does not appear to be associated with the development of
      depression. Thus, denying patients with significant acne an effective medication
      for fear of developing depression may not be indicated at this point in time.

PMID- 17556791
TI  - Cytokines, epilepsy and epileptic drugs--is there a mutual influence?
AB  - In recent years, the functional disturbances of the immune system, both humoral
      and cell-mediated immunity, have been detected more often among persons with
      epilepsy than in general population. A number of irregularities in cytokine
      production have been found in epileptic patients. It shows that epileptic
      seizures stimulate, per se, synthesis of pro-inflammatory and pro-convulsive
      cytokines. Some antiepileptic drugs (AEDs) influence the production of cytokines,
      too. The influence of AEDs on cytokine concentrations in blood has been observed,
      e.g. during carbamazepine (CBZ) or valproic acid (VPA) therapy. This article is a
      review of the literature which focuses on the connections between epilepsy and
      the cytokine system as well as on the influence of AEDs on the cell-mediated and
      humoral response in epileptic patients. Correlation of immunological
      irregularities in patients with the type, dosage, and serum level of AEDs will
      allow for early detection of undesirable treatment consequences in epilepsy.
      Elucidation of connections between cytokine system, epileptogenesis and
      effectiveness of AED therapy requires a better planned research on larger groups
      of patients with epilepsy.

PMID- 17556792
TI  - Hormonal supplementation in endocrine dysfunction in critically ill patients.
AB  - One of the greatest challenges for a physician is a critically ill patient.
      Regardless of the reason for an admission to the Intensive Care Units (ICU) (e.g.
      myocardial infarction, severe pneumonia, trauma or many others) each of the above
      mentioned conditions impairs homeostasis including instability of the endocrine
      system. The observed alterations in serum glucose level or clinical signs of
      hormonal imbalance alarm practitioners and prompt them to an intervention.
      However, side-effects of administered drugs have to be always considered, because
      every intervention in the endocrine system may have various consequences or prove
      itself maleficent. Since critical condition causes numerous changes in the
      hormonal system, the definition of endocrine gland failure in the ICU patients
      should differ from the definition related to the general population. This review
      is aimed at describing alterations, diagnosis and treatment options for an
      impaired carbohydrate metabolism and inadequate response of the adrenal and
      thyroid endocrine axis. It has been written in order to aid the choice between
      "the watch and wait strategy" and aggressive pharmacological intervention.
      Furthermore, several standard and innovative therapeutic procedures were
      described and, if possible, compared. Recent articles have been included in order
      to show current views on the up-to-date clinical approach.

PMID- 17556793
TI  - Versatile effects of sildenafil: recent pharmacological applications.
AB  - Sildenafil is a phosphodiesterase-5 (PDE5) inhibitor and is predominantly used in
      the treatment of erectile dysfunction. While maintaining an excellent safety and
      tolerability profile in the management of erectile dysfunction, sildenafil also
      provides a prolonged benefit in various other diseases. Sildenafil has been shown
      to have a potential therapeutic efficacy for disorders related to the central
      nervous system and pulmonary system. In the central nervous system, it exerts its
      neuroprotective effects in multiple sclerosis and has a significant memory
      enhancing action. Sildenafil also significantly enhances neurogenesis. Several
      lines of evidence indicate that targeting PDE5 with sildenafil offers novel
      strategies in the treatment of age-related memory impairment. Guanylate
      cyclase/cGMP/protein kinase G pathway or glutamate/nitric oxide/cGMP pathway
      appears to mediate memory enhancing effects. Some of the positive cognitive
      features of sildenafil therapy are likely attributable to the mechanisms reviewed
      here. Sildenafil has been shown to reduce pulmonary hypertension and alleviate
      pain in animals and humans. The present review primarily focuses on the various
      pharmacological effects of sildenafil with regard to its influence on the nervous
      and pulmonary system.

PMID- 17556794
TI  - Inhibitor of cyclooxygenase-2 protects against amyloid beta peptide-evoked memory
      impairment in mice.
AB  - Alzheimer's disease (AD) results in an impairment of memory and behavior. It is
      accepted that amyloid beta (A beta) peptides are responsible for the
      etiopathology of AD, but the precise signaling pathways leading to the disease
      have not been elucidated. In this study, we have investigated the role of
      cyclooxygenase-2 (COX-2) in A beta(1-42)-evoked memory impairment in mice.
      Moreover, the effect of systemic inflammation on A beta-dependent locomotor and
      memory disturbances has been evaluated. Twelve-month-old C57Bl6 mice were
      injected intracerebroventricularly (icv) with A beta(1-42) alone or
      simultaneously with intraperitoneal (ip) administration of lipopolysaccharide
      (LPS). Some mice also received COX-2 inhibitor, NS-398. Another group of mice was
      pretreated with LPS at 4 and 7 months of age, and then injected with A beta(1-42)
      at 12 months of age. All mice were subjected to behavioral tests one week after A
      beta administration. COX-2 protein level was analyzed in the hippocampus using
      immunochemical method. Our data demonstrated that A beta enhanced COX-2 protein
      level and decreased the locomotion and exploration in mice. Systemic inflammation
      elevated COX-2 immunoreactivity at an early stage after injection and intensified
      behavioral disturbances. Moreover, the object recognition in A beta-treated mice
      was significantly affected compared to control mice. The administration of LPS
      simultaneously with A beta worsened recognition performance. A COX-2 inhibitor
      protected mice against memory deficit and locomotor disturbances. In LPS
      pretreated animals, A beta induced locomotor disturbances, but had no effect on
      memory and COX-2 level. Our results indicate that A beta evokes enhancement of
      COX-2 protein level and memory deficit. Systemic inflammation modulates A beta
      effect on the brain function. The COX-2 inhibitor protects the brain against A
      beta-induced memory disturbances.

PMID- 17556796
TI  - Theophylline, adenosine receptor antagonist prevents behavioral, biochemical and
      neurochemical changes associated with an animal model of tardive dyskinesia.
AB  - Tardive dyskinesia is considered to be the late onset adverse effect of prolonged
      administration of typical neuroleptic drugs. Adenosine is now widely accepted as
      the major inhibitory neuromodulators in the central nervous system besides GABA.
      Antagonists of A2A receptors are known to confer protection against neuronal
      damage caused by toxins and reactive oxygen species. The present study
      investigated the effect of adenosine receptor antagonist, theophylline (25 and 50
      mg/kg, ip) in an animal model of tardive dyskinesia by using different behavioral
      (orofacial dyskinetic movements, stereotypy, locomotor activity, % retention),
      biochemical (lipid peroxidation, reduced glutathione levels, antioxidant enzyme
      levels (SOD and catalase)) and neurochemical (neurotransmitter levels)
      parameters. Chronic administration of haloperidol (1 mg/kg ip for 21 days)
      significantly increased vacuous chewing movements (VCMs), tongue protrusions,
      facial jerking in rats which was dose-dependently inhibited by theophylline.
      Chronic administration of haloperidol also resulted in the increased dopamine
      receptor sensitivity as evidenced by increased locomotor activity and stereotypic
      rearing. Further, it also decreased % retention time in elevated plus maze
      paradigm. Pretreatment with theophylline reversed these behavioral changes.
      Chronic administration of haloperidol also induced oxidative damage in all the
      brain regions which was prevented by theophylline, especially in the striatum.
      Chronic administration of haloperidol resulted in a decrease in dopamine levels
      which was reversed by treatment with theophylline (at higher doses). The findings
      of the present study suggested the involvement of adenosinergic receptor system
      in the development of tardive dyskinesia and possible therapeutic potential of
      theophylline in this disorder.

PMID- 17556795
TI  - Neurochemical and behavioral effects of 8-OH-DPAT following exposure to restraint
      stress in rats.
AB  - 8-Hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), a selective 5
      hydroxytryptamine 1A (serotonin; 5-HT1A) agonist was used to evaluate the role of
      somatodendritic and/or postsynaptic 5-HT1A receptors following exposure to
      restraint stress. Exposure to an episode of 2-h restraint stress decreased 24 h
      cumulative food intake. Intensity of 8-OH-DPAT-induced 5-HT syndrome monitored
      next day was smaller in restrained than unrestrained animals. Hyperphagic effects
      of 8-OH-DPAT were comparable in the two groups. Restrained animals injected with
      saline exhibited an increase in 5-HT levels in the hippocampus, hypothalamus and
      cortex but not in the midbrain and striatum. 5-Hydroxyindolacetic acid (5-HIAA)
      increased in the hippocampus, midbrain and cortex but not in the hypothalamus and
      striatum. 8-OH-DPAT injected at a dose of 0.25 mg/kg decreased 5-HT and 5-HIAA
      levels in different brain regions of unrestrained as well as restrained animals.
      The decreases were greater in restrained than unrestrained animals, suggesting a
      supersensitivity of somatodendritic 5-HT1A receptors. The results are discussed
      in the context of a role of 5-HT1A receptor in restraint-induced behavioral
      deficits.

PMID- 17556797
TI  - Role of phosphoinositide 3-kinase in ischemic postconditioning-induced
      attenuation of cerebral ischemia-evoked behavioral deficits in mice.
AB  - The present study has been designed to pharmacologically investigate the role of
      phosphoinositide 3-kinase in ischemic postconditioning-induced reversal of global
      cerebral ischemia and reperfusion-induced behavioral dysfunction in mice.
      Bilateral carotid artery occlusion for 10 min followed by reperfusion for 24 h
      was employed in the present study to produce ischemia and reperfusion-induced
      cerebral injury in mice. Short-term memory was evaluated using the elevated plus
      maze test. The inclined beam walking test was employed to assess motor
      incoordination. Bilateral carotid artery occlusion followed by reperfusion
      produced impaired short-term memory, motor co-ordination and lateral push
      response. Three episodes of carotid artery occlusion for a period of 10 s and
      reperfusion of 10 s (ischemic postconditioning) significantly prevented ischemia
      reperfusion-induced behavioral deficit measured in terms of loss of short-term
      memory, motor coordination and lateral push response. Wortmannin (2 mg/kg, iv), a
      phosphoinositide 3-kinase inhibitor given 10 min before ischemia attenuated the
      beneficial effects of ischemic postconditioning. It may be concluded that
      beneficial effects of ischemic postconditioning on global cerebral ischemia and
      reperfusion-induced behavioral deficits may involve activation of
      phosphoinositide 3-kinase-linked pathway.

PMID- 17556798
TI  - Polymorphism in the P-glycoprotein drug transporter MDR1 gene in renal transplant
      patients treated with cyclosporin A in a Polish population.
AB  - P-glycoprotein (P-gp), the product of MDR1 gene, is a protein which mediates
      transmembrane transport of a great number of xenobiotics including cyclosporin A
      used as an immunosuppressive drug in patients with allogenic kidney grafts. The P
      gp activity and expression is dependent on the MDR1 gene polymorphism in position
      C3435T of exon 26. In this study, C3435T polymorphism was analyzed in 116
      patients with allogenic kidney graft treated with cyclosporin Aand 144 randomly
      selected healthy individuals. The prevalence of MDR1 gene genotypes 3435CC,
      3435CT, 3435TT were also compared in patients after allogenic kidney graft with
      both acute and chronic graft rejection (48 patients with acute and 76 with
      chronic graft rejection) and control groups (respectively 139 and 112). The
      results of the study demonstrated that the allelic frequency and MDR1 genotype
      distribution were similar in all evaluated groups. It was revealed that MDR1 gene
      polymorphism was not a predisposing factor for terminal kidney failure leading to
      renal transplantation. Moreover, evaluation of C3435T polymorphism of MDR1 gene
      will probably not be useful for characterization of groups of patients at
      increased risk of acute and chronic kidney graft rejection.

PMID- 17556799
TI  - Toxicity of pyrimidine derivatives under oxidative stress conditions:
      chemiluminescence-based assays in systems containing erythrocytes, mitochondria
      or blood plasma.
AB  - Participation of mono-, di-, and tricyclic pyrimidine derivatives in free radical
      processes was investigated with the use of luminol-enhanced chemiluminescence in
      measurements performed in vitro in systems containing erythrocytes, erythrocyte
      lysate, erythrocyte membranes, mitochondria, mitoplasts or blood plasma. The free
      radical processes were induced in the investigated systems by tert -butyl
      hydroperoxide ( t -BuOOH) or 2,2'-azobis(2-amidinopropane) dihydrochloride
      (AAPH). Amongst the examined compounds, only derivatives containing the thiol
      substituent were found to modify the course of chemiluminescence. Effects of both
      amplification and inhibition of light emission were observed to depend on the
      structure of a derivative and on the type of a biological (experimental) system.
      The light emission-amplifying activity was found to be characteristic of the
      system containing erythrocytes. The results of the investigations point out that
      the pyrimidine thio-derivatives prolonged the oxidative stress through some
      interactions mainly with (oxy)hemoglobin, which was related with specific
      toxicity against erythrocytes. Model investigations in the proposed experimental
      systems can serve as a useful tool at early stages of the drug discovery process
      when compounds involved in the interactions connected with the oxidative stress
      are being selected. On the other hand, this method allows to study mechanisms of
      the toxic action of xenobiotics on cells (erythrocytes) and organelles
      (mitochondria), strongly implicated in the free radical generation, and to
      examine the role of the extracellular liquid (plasma).

PMID- 17556800
TI  - Cytotoxic activity of the selected pyridinium salts against murine leukemia
      L1210.
AB  - The objective of this work was to evaluate the relationship between chemical
      reactivity of 3-substituted pyridinium salts and their cytotoxic properties
      against murine leukemia L1210. Chemical reactivity of pyridinium salts towards
      NADH oxidation following one-step hydride transfer depends strongly on their
      redox properties. The investigated reaction may reflect the ability of the salts
      to deplete NADH level in cells and to affect their metabolic functions. On the
      other hand, the cytotoxic activity against murine leukemia cells, expressed as
      ED50 values, varied strongly depending upon the compound used. The investigated
      salts showed also a diverse antileukemic effect in in vivo experiments as
      measured by the increase in the survival time of L1210 leukemia-bearing mice.
      These biological effects were correlated with equilibrium constants found for the
      reaction of pyridinium salts with NADH.

PMID- 17556801
TI  - The short- and long-term effects of two isomers of DDT and their metabolite DDE
      on hormone secretion and survival of human choriocarcinoma JEG-3 cells.
AB  - JEG-3 cells were used to compare the effects of two isomers of DDT (1,1,1,
      trichloro-2,2-bis(p-chlorophenyl)ethane), p,p'-DDT and o,p'-DDT and their
      metabolite DDE (1,1,-dichloro-2,2-bis(p-chlorophenyl)ethylene) on progesterone
      (P4) and human chorionic gonadotropin (hCG) secretion and cell apoptosis. Cells
      were treated with 1, 10, 100 ng/ml or 1 mug/ml of each compound for 24 or 72 h.
      Twenty four hours of exposure at 1 mug/ml of p,p'-DDT and o,p'-DDT decreased,
      whereas both DDEs, at all investigated concentrations, increased P4 secretion.
      Seventy two-hour exposure to all concentrations of both isomers of DDT and their
      metabolite DDE stimulated progesterone secretion. Statistically significant
      decrease in hCG secretion after 24 h and increase in hCG secretion after 72 h
      exposure for all investigated compounds was noted. Decrease in caspase-3 activity
      was observed in cells exposed to both isomers of DDT and its metabolites. These
      findings indicate that both isomers of DDT and their metabolite DDE are able to
      alter main placental hormone production and survival of JEG-3 cells in the
      concentration- and time-dependent manner.

PMID- 17556802
TI  - Antiproliferative activity of parthenolide against three human cancer cell lines
      and human umbilical vein endothelial cells.
AB  - Parthenolide is a major sesquiterpene lactone derived from feverfew (Tanacetum
      parthenium) with known anti-inflammatory activity. Moreover, the anticancer
      potential of this compound was suggested. In this study, we determined the effect
      of parthenolide on proliferation of three human cancer cell lines: human lung
      carcinoma (A549), human medulloblastoma (TE671), human colon adenocarcinoma (HT
      29) and human umbilical vein endothelial cells (HUVEC) in vitro. Cell
      proliferation was assessed by means of 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide (MTT) assay. The IC(50) value (the concentration of
      drug necessary to induce 50% inhibition) together with confidence limits was
      calculated. Parthenolide inhibited proliferation of all three types of cancer
      cells (A549, TE671, HT-29) and HUVEC with the following IC(50) values (in muM):
      4.3, 6.5, 7.0 and 2.8, respectively. Thus, the antiproliferative potential of
      parthenolide was confirmed.

PMID- 17556803
TI  - Inhibitors of phosphatidylinositide 3-kinase: effects on reactive oxygen species
      and platelet aggregation.
AB  - Phosphoinositide 3-kinase (PI 3-kinase) exists in cells as a family of isoforms.
      The enzymes are important regulators of fundamental metabolic processes, such as
      energy utilization, growth, cell proliferation and survival. They are activated
      by cell surface receptors for hormones, and by G-protein coupled receptors.
      Enzyme p110 gamma, in particular, catalyzes production of second messengers from
      inositol phospholipids, including phosphoinositide (3,4,5) triphosphate or PtdIns
      (3,4,5) P3, PtdIns (3,4) P2 and Ptdins (3) P. The objective of this study was to
      corroborate the role of PI 3 kinase in ROS generation and in platelet aggregation
      through the use of four chemically unrelated inhibitors of PI 3 kinase:
      wortmannin, LY-294002, resveratrol and quercetin. In this study, we describe the
      effects of four PI 3-kinase inhibitors on the production of reactive oxygen
      species (ROS) and platelet aggregation induced by a diversity of agonists.
      Neutrophils and platelets were obtained from human blood and macrophages from
      mouse peritoneal cavity. ROS production was measured by a luminol-enhanced
      chemiluminescence assay; aggregation was measured in platelet-rich plasma (PRP)
      with a Chronolog Dual Channel Lumi-Aggregometer. Effects of graded concentrations
      of four enzyme inhibitors (wortmannin, LY-294002, resveratrol and quercetin) were
      evaluated. All inhibitors caused concentration-dependent depression of ROS
      generation and human platelet aggregation. They differed only in their potencies
      as revealed by concentration-response data. Moreover, inhibitors blocked activity
      of three chemically unrelated stimulants of aggregation: ADP, collagen and
      epinephrine. We conclude that inhibition of PI 3-kinase would appear to be a
      useful therapeutic goal in those conditions where the activities of platelets
      and/or phagocytes become aberrant.

PMID- 17556804
TI  - Arabidopsis replication factor C subunit 1 plays an important role in
      embryogenesis.
AB  - Replication factor C (RFC), consisting of one large subunit and four small
      subunits, is an important factor involved in DNA replication and repair
      mechanisms as well as cell proliferation. The subunit 1 of Arabidopsis RFC
      (AtRFC1) is a homologue of p140, the large subunit of human RFC. Three T-DNA
      insertion mutant lines of AtRFC1, i.e. rfc1-1, rfc1-2 and rfc1-3, with insertion
      mutations located in exons 16 and 19, and the promoter region respectively were
      verified. These mutations caused defects in embryogenesis and led to embryo and
      seed abortion. Transformation of wild type AtRFC1 gene into rfc1 mutant alleles
      reverted the mutant phenotypes, suggesting that AtRFC1 plays an important role in
      embryo development in Arabidopsis thaliana.

PMID- 17556805
TI  - [Genetic transformation of OSISAP1 gene to onion (Allium cepa L.) mediated by
      amicroprojectile bombardment].
AB  - Microprojectile bombardment-mediated transformation method has been developed for
      onion (Allium cepa L.) using embryogenic calli, induced from stem discs, as
      target tissue. Zinc-finger protein gene OSISAP1 (Oryza sative subspecies indica
      stress-associated protein gene) was introduced into the open-pollinated onion
      cultivar (subs.) 'HG400B'. Bombardment parameters were optimized as: the pressure
      is 1,100 psi, the distance is 6 cm, two times, the ratio of mass between plasmid
      DNA and golden particles is 1:320. An efficient microprojectile bombardment
      mediated transformation system of onion (Allium cepa L.) callus has been
      established. The binary vector used carried the nptII gene for kanamycin
      resistance and the GUS reporter gene. Transgenic cultures were screened for their
      ability to express the GUS reporter gene and to grow in the presence of kanamycin
      (150 mg/L). Transient expression of GUS reporter gene was observed through
      histochemical staining of embryogenic callus transformed by microprojectile
      bombardment. The putative transgenic plants were analysed at the molecular level
      using PCR, southern hybridization, and RT-PCR. The results confirmed that the
      OSISAP1 gene was integrated as one copy into the genome of onion and expression.
      Transgenic plants were produced efficiently with a transformation frequency of
      about 10%. Test of salinity-alkali stress showed that sodium chloride and sodium
      bicarbonate at 200 mmol/L effectively killed non-transgenic plants within 1 week
      of irrigation, while the transgenic plants were completely unaffected by salinity
      of 400 mmol/L. So transformation with the OSISAP1 gene raised the salinity-alkali
      tolerance of the transgenic plants to a high level.

PMID- 17556806
TI  - Cloning and expression of the chloroplast copper/zinc-superoxide dismutase gene
      in upland cotton (Gossypium hirsutum L.).
AB  - A full-length 1,043-base-pair cDNA clone encoding a chloroplast copper/zinc
      superoxide dismutase (Cu/Zn-SOD) of upland cotton was first isolated by rapid
      amplification of cDNA ends (RACE) from the leaves of the cotton (Gossypium
      hirsutum L.) variety 'CRI36'. Nucleotide sequence analysis of the clone revealed
      that it contained the complete coding sequence of the mature SOD isozyme subunit,
      along with a 60-amino acid transit peptide at N-terminal. The amino acid sequence
      predicted from the full-length clone showed 66%-74% homology with the amino acid
      sequences of Cu/Zn-SOD from several other plants. This gene was found to be
      expressed in the leaves and stems, but not in roots, flowers, and hypocotyls,
      indicating that the gene was expressed only in green tissues. Also, its
      expression was found to be most active at seedling stage and declined gradually
      in later development stages. Expression of this cotton Cu/Zn-SOD gene by using
      the pET-21a (+) expression vector in E. coli BL21 (DE3) led to the production of
      a novel 29 kD polypeptide with SOD enzyme activity, confirming that the cloned
      cotton Cu/Zn-SOD cDNA was indeed encoding a functioning SOD enzyme.

PMID- 17556807
TI  - Effects of post-harvest light conditions on quality and aromatic volatile
      formation in 'Hakuho' peach (Prunus persica Batsch) fruits.
AB  - The effect of light condition during post-harvest storage on fruit quality of
      'Hakuho' peach (Prunus persica Batsch) was examined. Fruits were harvested at the
      immature stage (7 d before the tree-ripening stage) and firm-ripe (3 d before the
      tree-ripening) stage and stored at 25 degrees C under light (ca 80 micromol m(-2)
      s(-1) at the fruit top by a fluorescent lamp) and in darkness. The light and dark
      conditions did not significantly influence the ethylene production rate except
      for the fully ripened fruits harvested at firm-ripe stage and stored under light.
      However, no difference in fruit firmness was detected among treatments at full
      ripe stage. The skin anthocyanin content increased significantly during storage
      under light. Total soluble solid (TSS) content of juice at the full ripe stage
      was not affected significantly by the storage condition, although titratable
      acidity (TA) in immature harvested fruits decreased more quickly during storage
      under light compared with those stored in darkness. Dark storage limited the
      decrease in juice asparagine to some extent. Aromatic lactones, such as gamma
      decalactone and gamma-dodecalactone, both in skin and in flesh tissues increased
      more rapidly when the fruits were stored under a light condition, irrespective of
      fruit harvest stage. From these results, we conclude that fruit storage under a
      light condition is better for fruit quality of the 'Hakuho' peaches than storage
      in darkness.

PMID- 17556808
TI  - [The control of sugar accumulation within strawberry aggregate fruit by invertase
      and hexokinase].
AB  - The glucose, fructose and sucrose contents and the activities of invertase,
      sucrose synthase (SS), sucrose phosphate synthase (SPS), hexokinase (HXK) and
      fructokinase (FRK) of 'Tochiotome' strawberry aggregate fruit were analyzed at
      various stages of fruit development. The sugar accumulation exhibited the
      difference between various parts of the fruit. The sugar content is the highest
      in the top part of ripe 'Tochiotome' strawberry aggregate fruit, followed by the
      central part, and the basal part was the lowest. Changes in activity of invertase
      corresponded to the changes of sugar concentration gradient within various parts
      of the ripe strawberry aggregate fruit. The SS and SPS activities within various
      parts of aggregate fruit did not showed obvious change that corresponded to the
      sugar content. At the stage of fruit maturation, the HXK and FRK activities
      within various parts of strawberry aggregate fruit, however, exhibited an
      opposite gradient to sugar content. The basal part of aggregate fruit had the
      highest activities of HXK and FRK, while the top part had the lowest activities.
      These results suggested that the higher activity of invertase in the top part of
      aggregate fruit may play a role for rapid cleavage of sucrose and help to form a
      sucrose gradient in apoplastic space from the basal part to the top part of
      strawberry aggregate fruit, thus enhance photosynthate translocation from the
      basal part to the top part of aggregate fruit, which led to higher sugar
      accumulation in the top part of fruit. In the basal part of aggregate fruit, the
      higher activities of hexose-metabolizing enzymes may promote the consumption of
      hexose, and thus resulted in the lowering of sugar content in the basal part than
      in the top part of strawberry aggregate fruit.

PMID- 17556809
TI  - [Analysis of genomic DNA methylation level in radish under cadmium stress by
      methylation-sensitive amplified polymorphism technique].
AB  - The level of cytosine methylation induced by cadmium in radish (Raphanus sativus
      L.) genome was analysed using the technique of methylation-sensitive amplified
      polymorphism (MSAP). The MSAP ratios in radish seedling exposed to cadmium
      chloride at the concentration of 50, 250 and 500 mg/L were 37%, 43% and 51%,
      respectively, and the control was 34%; the full methylation levels (C(m)CGG in
      double strands) were at 23%, 25% and 27%, respectively, while the control was
      22%. The level of increase in MSAP and full methylation indicated that de novo
      methylation occurred in some 5'-CCGG sites under Cd stress. There was significant
      positive correlation between increase of total DNA methylation level and CdCl(2)
      concentration. Four types of MSAP patterns: de novo methylation, de-methylation,
      atypical pattern and no changes of methylation pattern were identified among
      CdCl(2) treatments and the control. DNA methylation alteration in plants treated
      with CdCl(2) was mainly through de novo methylation.

PMID- 17556810
TI  - A calcium-dependent protein kinase is involved in plant hormone signal
      transduction in Arabidopsis.
AB  - A number of signal pathways have been found through which abundant calcium
      stimulated protein kinase activity in plant is associated with calcium-dependent
      protein kinases (CDPKs) which act as the calcium sensors mediating numerous
      responses, including hormone signaling. Basing on previous studies, we made
      additional functional analysis of the gene AtCPK30 encoding a protein kinase in
      Arabidopsis. Results of semi-quantitative reverse transcription PCR (RT-PCR)
      analysis indicated that AtCPK30 was highly expressed in root and induced by ABA,
      IAA, 2,4-D, GA(3) and 6-BA treatment. The physiological roles of AtCPK30 were
      studied using a gain-of-function approach. Seedlings of AtCPK30 transgenic lines
      had longer primary roots than those plants of wild-type at the early stages.
      Interestingly, when these plants grew on MS lack of Ca(2+) including wild-type
      and transgenic lines, the roots of transgenic line were more sensitive to
      calcium, lack of Ca(2+) had less effect on roots of transgenic lines than those
      of wild-type. Treated with several plant hormones, such as ABA, IAA, GA(3) and 6
      BA, the roots of seedlings of transgenic line developed abnormally because they
      were more sensitive to hormones. Furthermore, NPA relatively less inhibited
      emergency of lateral roots of transgenic line than those of the wild-type. Green
      fluorescent protein-CPK30 (GFP-CPK30) fusion protein studies revealed the
      localization of AtCPK30 to both cell wall and plasma membrane. These results
      suggest that AtCPK30 acts as the calcium sensor and involved in the hormone
      signaling pathways.

PMID- 17556811
TI  - Relationship between grain yield and leaf photosynthetic rate in super hybrid
      rice.
AB  - In order to explore the relationship between grain yield and photosynthesis, the
      yield composition and leaf photosynthetic rate in some super hybrid rices and
      ordinary hybrid rice 'Shanyou 63' as control were measured in 2000-2005. The
      results were as follows. (1) The yield levels of the four super hybrid rices,
      'Pei'ai 64S/E32', 'P88S/0293', 'Jin23A/611' and 'GD-1S/RB207', were significantly
      higher, being 108%-120% of 'Shanyou 63'. (2) These super hybrid rices had a
      better plant type with more erect upper layer leaves and bigger panicles or more
      spikelets per panicle, being 125%-177% of spikelets Shanyou 63 spikelets. (3) Net
      photosynthetic rates of these super hybrid rices were significantly higher in the
      second leaf but not necessarily in the first leaf or flag leaf than those of
      spikelets Shanyou 63 spikelets. (4) The removal of half flag leaf led to a
      decline in the seed-setting rate, while the removal of half panicle induced its
      increase in spikelets GD-1S/RB207 spikelets. Hence, higher yield in these super
      hybrid rices can be attributed to their bigger panicles, better plant type and
      higher light use efficiency of their canopies. Raising the photosynthetic
      capacity of each leaf, especially flag leaf, is the key to overcome the
      photosynthate-source restriction on grain yield and to make a new breakthrough of
      yield potential in future breeding of super hybrid rice.

PMID- 17556812
TI  - Priming of seeds with nitric oxide donor sodium nitroprusside (SNP) alleviates
      the inhibition on wheat seed germination by salt stress.
AB  - The effect of SNP, an NO donor, on seed germination of wheat (Triticum aestivum
      L. cv. 'DK961') under salt stress was studied. The results showed that priming of
      seeds with 0.06 mmol/L SNP for 24 h markedly alleviated the decrease of the
      germination percentage, germination index, vigor index and imbibition rate of
      wheat seeds under salt stress. SNP significantly alleviated the decrease of the
      beta-amylase activity but almost did not affect the alpha-amylase activity of
      wheat seeds under salt stress. SNP slightly increased the alpha-amylase
      isoenzymes (especially isoenzyme 3) and significantly increased the beta-amylase
      isoenzymes (especially isoenzyme d, e, f and g). SNP pretreatment decreased Na(+)
      content, but increased the K(+) content, resulting in a mark increase of
      K(+)/Na(+) ratio of wheat seedlings under salt stress. These results suggested
      that NO is involved in promoting wheat seed germination under salt stress by
      increasing the beta-amylase activity.

PMID- 17556813
TI  - [Expression of the GUS fusion gene controlled by the tomato rbcS3A promoter in
      transgenic rice].
AB  - To use different types of promoters in transgenic rice research, the 1.1 kb 5'
      upstream regulation region of one of the tomato (Solanum tuberosum L.) Rubisco
      small subunit gene, rbcS3A, was cloned and its sequences were confirmed by
      comparison with the known sequences in GenBank. The cloned rbcS3A promoter was
      fused to the 5'-upstream of GUS (beta-glucuronidase) coding region in a binary
      vector, and introduced into an elite japonica rice variety by Agrogacterium
      mediated transformation. The integration of the GUS fusion gene into the genome
      of transgenic rice was confirmed by both PCR and Southern blot analysis. The
      results of both histochemical staining and quantitative analysis of GUS activity
      showed that the expression level of GUS fusion gene was significantly stronger in
      stem, leaf blade and sheath than in other organs of transgenic rice plants, and
      showed highest in the stem, which implies that the tomato rbcS3A promoter can
      make tissue-specific, in particular in the stem, expression of foreign genes in
      transgenic rice. The results present here also demonstrate that light induction
      had no effect on the expression of the foreign gene when regulated by the tomato
      rbcS3A promoter in transgenic rice. Our results show that the cloned tomato
      rbcS3A promoter might be very useful for the expression of target genes in
      transgenic rice, with particularly high efficiency in stem tissues.

PMID- 17556814
TI  - [The application of two-dimensional liquid phase chromatography to separation of
      total protein of Leymus chinensis shoot].
AB  - The total proteins of Leymus chinensis were extracted from eight-week-old
      seedlings grown in the greenhouse by TCA-acetone precipitation method. After the
      lysis buffer was replaced by the start buffer, proteins were fractionated along
      the first dimension using chromatofocusing (CF). Subsequently the fractions with
      pI values between 8.5 and 4.0 collected after the first dimension separation were
      further fractionated by nonporous silica reverse-phase high-performance liquid
      chromatography (NPS-RP-HPLC, HPRP). With ProteoVue software the pI/UV map was
      generated to show the protein expression profile of Leymus chinensis. Some
      experiments were tested to optimize the fraction procedure. Three different
      elution gradients were employed to get the optimal chromatogram. Comparison of
      the protein expression pattern between 2D-PAGE and 2D-LC indicated that 2D-LC was
      a powerful tool in protein fraction. Reproducibility and veracity of the protein
      patterns were confirmed in different injections of the same sample. A method to
      fractionate the total protein of Leymus chinensis shoot with two-dimensional
      liquid chromatography (2D-LC) was founded.

PMID- 17556816
TI  - Congenital posthemorrhagic hydrocephalus: a case of fetomaternal alloimmune
      thrombocytopenia.
AB  - Fetal/neonatal alloimmune thrombocytopenia (NAIT) results from fetomaternal
      mismatch for human platelet alloantigens leading to antibody-mediated destruction
      of fetal platelets. This is one of the most common causes of severe
      thrombocytopenia in the newborn with an incidence of 1/800-1,000. In the most
      severe cases, NAIT may result in intracranial hemorrhage and may lead to death or
      neurologic sequelae. We report a case of fetal hydrocephalus caused by NAIT and
      discuss the importance of making an accurate prenatal diagnosis to improve the
      management of the current pregnancy and the outcome of subsequent pregnancies.
      Screening of female siblings of affected cases is recommended in order to detect
      at-risk individuals.

PMID- 17556817
TI  - Successful intrauterine therapy for congenital cystic adenomatoid malformation of
      the lung. A case report.
AB  - Congenital cystic adenomatoid malformation (CCAM) of the lung is a rare
      abnormality which is amenable to be diagnosed by prenatal ultrasonography. In
      general, CCAM associated with non-immune hydrops has a poor prognosis unless a
      fetal intervention is performed. In some series almost 100% of either prenatal or
      early neonatal deaths are observed without intervention. Recently the cystic
      adenomatoid malformation volume ratio (CVR) has been proposed as an index to
      predict the development of hydrops in this condition. If the CVR is >1.6, the
      risk of hydrops is approximately 75%. We report a case of CCAM (macrocystic type)
      of the left lung referred to our center at 21 weeks of gestation. Fetal therapy
      was considered owing to enlargement of the CCAM volume, severe mediastinal shift,
      right lung compression, polyhydramnios and ascites from 21 to 26 weeks.
      Thoracoamniotic shunting was performed successfully at 26 weeks with resolution
      of the cystic mass. At 37 weeks a male infant was born vaginally weighing 3,210 g
      with Apgar scores of 5 and 10. Resection of the mass was performed uneventfully
      on day 3. The infant is currently 22 months of age, asymptomatic and in good
      condition.

PMID- 17556818
TI  - Proposal of a diagnostic test for the detection of preterm premature rupture of
      membranes based on the determination of thyroid hormones in vaginal washing
      fluid.
AB  - OBJECTIVES: To determine whether measurement of total T3 (triiodothyronine) ,
      total T4 (thyroxine), free T3 (free triiodothyronine) and free T4 (free
      thyroxine) levels in vaginal fluid is useful for the diagnosis of preterm
      premature rupture of membranes (PPROM). STUDY DESIGN: The PPROM group and normal
      pregnancy group consisted of 30 and 30 pregnant patients between 26 and 36 weeks'
      gestation, respectively. Vaginal fluid total T4, free T4, total T3 and free T3
      levels were measured in both groups. RESULTS: Vaginal fluid total T3 and free T3
      levels were not statistically significant in the PPROM group as compared with the
      control group (p = 0.087, p = 0.123, respectively). Vaginal fluid total T4 and
      free T4 levels were significantly higher in the PPROM group as compared with the
      control group (p = 0.002, p < 0.000, respectively). The optimal cut-off value for
      total T4 (0.866 mug/dl) gave a sensitivity level of 83.3% (65.3-94.3, 95% CI) at
      a specificity of 60.0% (40.6-77.3, 95% CI) with positive and negative predictive
      values of 67.6 and 78.3%, respectively. The optimal cut-off value for free T4
      (0.079 ng/dl) gave a sensitivity level of 90% (73.4-97.8, 95% CI) at a
      specificity of 70.0% (50.6-85.2, 95% CI) with positive and negative predictive
      values of 75.0 and 87.5%, respectively. CONCLUSIONS: Total and free T4
      measurements from vaginal fluids appears to be a useful marker of PPROM.

PMID- 17556819
TI  - Aortico-right ventricular tunnel: prenatal diagnosis leading to neonatal
      survival.
AB  - In the 36th week of gestation a large aortico-right ventricular tunnel with an
      otherwise structurally normal heart was diagnosed by fetal echocardiography. This
      report describes for the first time the impact of the timely prenatal diagnosis
      of an aortico-right ventricular tunnel followed by successful management in early
      infancy.

PMID- 17556820
TI  - An ethically justified decision-making pathway for the management of pregnancies
      complicated by twin-to-twin transfusion syndrome.
AB  - OBJECTIVE: To present an ethically justified decision-making pathway to use in
      the evaluation and treatment of pregnant women whose fetuses have twin-to-twin
      transfusion syndrome (TTTS). METHODS: The ethical principles of beneficence,
      autonomy and professional integrity were applied to the diagnostic and treatment
      options for TTTS. RESULTS: An algorithm was developed that includes the use of
      directive and non-directive counseling which can be used as a guide for informed
      consent of women whose pregnancies have TTTS. CONCLUSION: Ethics is an essential
      component of decision making for both pregnant women and their obstetricians in
      pregnancies complicated by TTTS.

PMID- 17556821
TI  - Intracranial hemorrhage and hydrops in the fetus of a mother with thrombocytosis:
      implications for possible pathogenetic factors and therapy.
AB  - We report a case of prenatally diagnosed intracranial hemorrhage and hydrops in
      the fetus of a mother with a past history of surgical and medical treatment for
      gastric lymphoma and having high platelet counts thereafter. To the best of our
      knowledge, such a complication of maternal thrombocythemia has not been described
      in the literature. In our opinion, the possible pathophysiology of the disease is
      based on placental insufficiency due to infarctions and related fetal platelet
      dysfunction, leading to intracranial hemorrhage with subsequent hydrops fetalis.
      The trigger in this event appears to be trauma to the maternal abdomen. Certain
      measures for high-risk mothers such as avoidance of trauma to the abdomen and
      platelet-lowering medications like interferon-alpha may be useful for preventing
      such fetal complications.

PMID- 17556822
TI  - Does a myelomeningocele sac compared to no sac result in decreased postnatal leg
      function following maternal fetal surgery for spina bifida aperta?
AB  - OBJECTIVE: A fetus with large sac S1 myelomeningocele (MMC) but bilateral talipes
      prompted the question, 'Does the presence or size of an MMC sac affect postnatal
      leg function?' STUDY DESIGN: An MMC database with prenatal, birth, and a minimum
      of 1-year follow-up evaluation was reviewed. All fetuses had in-utero MMC repair
      at 20 + 0 to 25 + 6 weeks at a single institution. Fifty-four fetuses had
      prenatal evaluation, with 48 children completing a birth and a 1-year evaluation
      of leg function. RESULTS: An MMC sac was present in 38/54 (70%) of fetuses
      evaluated in-utero and had been present in 35/48 (73%) of children evaluated at 1
      year of age. Although leg function evaluated at 1 year was better than expected
      in the 'no sac' group (p = 0.059), this did not reach statistical significance.
      CONCLUSION: The presence of an MMC sac may increase postnatal lower limb
      morbidity.

PMID- 17556823
TI  - Gastroschisis: growth patterns and a proposed prenatal surveillance protocol.
AB  - OBJECTIVE: To assess intrauterine growth for fetuses with gastroschisis using
      retrospective serial ultrasound assessment from fetuses diagnosed prenatally with
      gastroschisis. The growth assessment could be available as a prospective tool to
      direct an antepartum fetal surveillance protocol. METHODS: This is a
      retrospective review of all cases of gastroschisis evaluated prenatally at a
      single institution between February 1996 and March 2002. Charts were reviewed for
      serial ultrasound assessment, gestational age at delivery, mode of delivery, and
      birth weight. Growth assessment was determined for abdominal circumference,
      biparietal diameter, head circumference, femur length, and estimated fetal weight
      (IRB No. 2002-1-2648). RESULTS: Forty patients had delivered by March 2002. One
      hundred and two ultrasound reports were reviewed. Gastroschisis growth curves
      showed that the 50th percentile was shifted to the right when compared to normal
      growth curves for abdominal circumference, biparietal diameter, head
      circumference, and femur length. The average birth weight was 2,359 g. Compared
      with a standard population, 44% (16/36) were below the 5th percentile, 61%
      (22/36) were below the 10th percentile, and 95% (34/36) were below the 50th
      percentile for gestational age. The average gestational age at delivery was 36.3
      weeks. Mothers were nulliparous in 78%, with a mean age of 21.3 years.
      CONCLUSIONS: (1) Fetuses with gastroschisis show a symmetric intrauterine growth
      restriction pattern consistent with early development of growth delay; (2) the
      50th percentile biometry measurements for the gastroschisis population are
      shifted to the right on normal fetal growth curves; (3) the birth weight is at or
      below the 10th percentile in 61% of the newborns with gastroschisis, and (4) an
      antepartum surveillance protocol is proposed based on growth patterns of fetuses
      with gastroschisis.

PMID- 17556824
TI  - Umbilical cord insertion to the lower uterine segment is a risk factor for vasa
      previa.
AB  - The perinatal mortality rate of vasa previa is high if it is not prenatally
      diagnosed. Systematic strategies for vasa previa screening have been recommended.
      In this paper, three cases of vasa previa diagnosed prenatally, with umbilical
      cord inserted to the lower segment of the uterus, are presented. It should be
      considered that umbilical cord insertion to the lower uterine segment is a high
      risk for vasa previa. Ultrasound screening for cord insertion will make it
      possible to do efficient and certain detection of vasa previa.

PMID- 17556825
TI  - Prenatal genomic profiling of abdominal wall defects through comparative genomic
      hybridization: perspectives for a new diagnostic tool.
AB  - OBJECTIVES: To describe the molecular analysis through comparative genomic
      hybridization (CGH) of fetuses with gastroschisis, and to observe if this
      technique could improve the resolution of the conventional cytogenetic
      techniques. METHODS: Amniotic analysis of fetuses with gastroschisis, using both
      conventional (G-banding) and molecular (CGH) cytogenetics assays. RESULTS: All of
      the seven fetuses studied displayed a normal G-band karyotype. Six fetuses
      displayed a normal disomic profile through CGH and one sample has displayed ish
      cgh enh 3q26-->qter result (ICSN). The fetus with this imbalance of chromosome 3
      was re-classified as a ruptured omphalocele, instead of gastroschisis, after
      birth. CONCLUSIONS: The molecular investigation through CGH technique can improve
      the resolution of the conventional karyotye analysis in cases of abdominal wall
      defects.

PMID- 17556826
TI  - Effect of maternal betamethasone administration on prenatal congenital cystic
      adenomatoid malformation growth and fetal survival.
AB  - OBJECTIVE: To evaluate the effect of prenatal steroid treatment on the growth of
      congenital cystic adenomatoid malformations (CCAM) and survival in affected
      fetuses not amenable to other percutaneous ultrasound-guided prenatal
      interventions. METHODS: A retrospective review of patients with a CCAM or hybrid
      lesion treated with two maternal prenatal betamethasone injections was performed.
      Patients receiving cyst aspiration or thoracoamniotic shunting at the time of or
      after steroid administration were excluded. Growth rates and survival data were
      compared to historical non-steroid treated controls. RESULTS: Eleven patients
      were treated with prenatal steroids (10 microcystic and 1 macrocystic). Survival
      was 100% in fetuses with hydrops (5/5) or a CCAM volume ratio (CVR) >1.6 (7/7) at
      the time of steroid administration. This compares to a mortality of 100 and 56.2%
      respectively in historical non-treated controls. Resolution of hydrops was seen
      in 80% (4/5) of steroid-treated patients. CCAM growth rates were variable after
      steroid administration. However, when compared to historical data where CVR and
      CCAM volume have been documented to increase until 28 weeks' gestation, the CVR
      and CCAM volume growth rates decreased in 72.73% and 50% of patients respectively
      from the time of steroid administration to 28 weeks' gestation. CONCLUSIONS: In
      the fetus with a CCAM, the presence of hydrops fetalis or a CVR >1.6 is
      indicative of poor fetal outcome without prenatal intervention. The observed
      effect of antenatal steroid treatment on CCAM growth is variable, but its
      potential to improve survival in these high-risk groups is encouraging and
      warrants further controlled evaluations.

PMID- 17556827
TI  - The influence of assisted reproductive technology on growth discordance in
      dichorionic twin pregnancies.
AB  - OBJECTIVE: We examined the relation between first-trimester crown-rump length
      (CRL) discordance and birth weight discordance in dichorionic twin pregnancies
      conceived by assisted reproductive technology (ART). METHODS: We examined 101
      nulliparous dichorionic twin pregnancies producing male-male or female-female
      infants conceived spontaneously (n = 38) or following in vitro fertilization and
      embryo transfer (n = 63). RESULTS: There were no significant differences in CRL
      disparity or birth weight discordance between spontaneous and ART-conceived
      dichorionic twin pregnancies. There was a positive correlation between CRL
      disparity and birth weight discordance in ART-conceived twin pregnancies (r(2) =
      0.22, p = 0.02), while there was no such correlation in spontaneous pregnancies
      (r(2) = 0.02, p = 0.40). CONCLUSION: In ART-conceived dichorionic twin
      pregnancies, CRL disparity may be associated with birth weight discordance.

PMID- 17556828
TI  - Detection of fetal sex in the peripheral blood of pregnant women.
AB  - OBJECTIVE: To choose the best method to examine fetal sex in maternal blood as
      early as possible and evaluate the quantitative change of fetal-free DNA in
      maternal plasma. METHOD: One hundred and fifty pregnant women were studied at 5-9
      completed weeks of gestation. Fetal cells were isolated using lymphocyte
      separation liquid and 3% gelatin. Furthermore, fluorescence in situ hybridization
      was used to examine the terminal of the Y chromosome. Nested polymerase chain
      reaction (PCR) and real-time fluorescence quantitative PCR (FQ-PCR) were used to
      amplify the SRY gene of the plasma DNA extracted from the same 150 samples of
      maternal blood. Sequential analysis was performed using FQ-PCR during the whole
      pregnancy on 32 pregnant women carrying male fetuses. RESULTS: Using fluorescence
      in situ hybridization, we can find male fetal cells in maternal blood as early as
      the 49th day. We can also find free fetal DNA in maternal plasma as early as the
      49th and the 42nd day of pregnancy using nested PCR and FQ-PCR. The amount of
      fetal DNA was increasing with the gestation week. The standard value of every
      gestation week was obtained by FQ-PCR. CONCLUSION: FQ-PCR was the best method to
      detect fetal sex in early pregnancy. There is a principle of quantitative change
      of free fetal DNA in maternal plasma.

PMID- 17556829
TI  - Fetus-in-fetu: parasite or neoplasm? A study of two cases.
AB  - INTRODUCTION: Fetus-in-fetu is a rare congenital fetiform mass whose etiology is
      still controversial. We report two cases of fetus-in-fetu. CASE 1: A fetal
      retroperitoneal cystic tumor including two masses was detected by ultrasonography
      at 26 gestational weeks. The masses showed distinctive structures resembling a
      vertebral axis and were prenatally diagnosed as fetus-in-fetu. A resected
      specimen revealed two fetiform masses. CASE 2: An intracranial tumor with
      hydrocephalus was detected by ultrasonography at 19 gestational weeks. The
      pregnancy was terminated, and a postmortem examination revealed six fetiform
      masses with immature teratoma. DISCUSSION: The tumors may possibly consist of
      parasitic monozygotic diamniotic twins or highly differentiated teratomas.

PMID- 17556830
TI  - Discordant semilobar holoprosencephaly in monozygotic twins with de novo inv
      dup(15) marker chromosome and de novo mutation on SHH gene.
AB  - We present a 30-year-old woman with a twin pregnancy, 1 fetus displaying a small
      head circumference, semilobar holoprosencephaly, and cleft lip as detected by
      ultrasound at 23 weeks of gestation. Fetal magnetic resonance imaging confirmed
      the diagnosis of semilobar holoprosencephaly. The other twin, however, had an
      appropriate fetal growth, devoid of any major structural anomalies. Karyotyping
      by G-banding of amniocentesis specimens in both fetuses showed 47,XY,+mar.
      Fluorescence in situ hybridization showed in the marker chromosome positive
      dicentric signals for the chromosome 15 centromere-specific alpha satellite DNA
      probe (D15Z1) and negative signals for the SNRPN probe (15q11-13), thus
      establishing a cytogenetic diagnosis of 47,XX,+mar.ish idic(15)(q11
      q13)(D15Z1++,SNRPN-) for both fetuses. The parental karyotypes were normal. The
      fetuses, therefore, had a de novo inv dup(15) marker chromosome without
      involvement of the Prader-Willi region. Short tandem repeat markers (total 15
      markers) confirmed that the fetuses were monozygotic twins. Short tandem repeat
      markers at the 15q region (total 6 markers) excluded the possibility of
      uniparental disomy (15) mat or uniparental disomy (15) pat. Molecular study in
      both fetuses of TGIF, SHH, SIX3, and ZIC2 genes revealed a heterozygous 1085 C >
      T (Ser 362 Leu) on the SHH gene, but a homozygous 1085 C > C (Ser 362 Ser) for
      both parents on the SHH gene. The couple decided to terminate the pregnancy at 26
      weeks of gestation. To our knowledge, this is the first report of semilobar
      holoprosencephaly with inv dup(15) marker chromosome and missense SHH gene
      mutation 1085 C > T (Ser 362 Leu).

PMID- 17556831
TI  - Safety of chorionic villus sampling in the presence of asymptomatic subchorionic
      hematoma.
AB  - OBJECTIVE: According to our knowledge the safety of chorionic villus sampling
      (CVS) has not been studied in the presence of subchorionic hematoma (SCH). Our
      study aimed to evaluate the effects of CVS on the procedure-related fetal loss
      rate in patients with SCH. METHOD: Fifty-six patients with asymptomatic SCH
      (cases) and 986 controls in whom there was no hematoma underwent elective CVS for
      a prenatal diagnosis of beta-thalassemia and were entered into a prospective
      study. Mean gestational age (+/-SD) at diagnosis for the case and control groups
      were 11.07 weeks (+/-0.95, range 10-13 weeks) and 11.51 weeks (+/-1.04, range 10
      13 weeks), respectively. Procedural fetal loss rates were evaluated in these
      groups after follow-up until 28 weeks of gestation. RESULTS: The average hematoma
      volume (+/-SD) was 1.83 ml (+/-1.57, range 0.3-10.0 ml). Post-CVS early fetal
      loss was seen in 3.57% (2/56) of patients in the case group and 1.62% (16/986) of
      patients in the control group. Late fetal loss (up to the 28th week) in the case
      and control groups was 8.16% (4/49) and 3.76% (29/771), respectively. Post-CVS
      early fetal loss was seen in 2.44% (1/41) of patients with small-sized SCH (<20%
      of gestational sac circumference) and in 6.67% (1/15) of patients with medium
      sized SCH (20-50% of gestational sac circumference). Comparison of procedure
      related early and late fetal loss in the case and control groups using Fisher's
      exact test demonstrated no statistically significant difference (p value = 0.252,
      p value = 0.128). Difference in CVS-related early fetal loss in small- and medium
      sized hematoma groups (6.67 vs. 2.44%) was not significant either (p value =
      0.468). CONCLUSION: We were unable to detect any statistically significant
      difference in fetal loss rate after performing CVS in patients with SCH in
      comparison to the control group. However, it seems that fetal loss rate may be
      higher in the presence of medium-sized (20-50% of gestational sac circumference)
      SCH and further cases are necessary to evaluate the safety of doing CVS in this
      group.

PMID- 17556832
TI  - Development of fibre-optic confocal microscopy for detection and diagnosis of
      dental caries.
AB  - We report on the development of a fibre-optics-based confocal imaging system for
      the detection and potential diagnosis of early dental caries. A novel optical
      instrument, capable of recording axial profiles through caries lesions using
      single-mode optical fibres, has been developed. The practical study illustrates
      that miniature confocal devices based around single-mode optical fibres may
      provide additional diagnostic information for the general dental practitioner.

PMID- 17556833
TI  - Root surface caries in older individuals from Sri Lanka.
AB  - The aim of the present study was to assess the prevalence and factors associated
      with root surface caries in older individuals from Sri Lanka. A total of 600
      urban subjects aged 60 years and above was selected using a two-stage cluster
      sampling combined with probability-proportionate-to-size technique. The data were
      collected by means of an interviewer-administered questionnaire and an oral
      examination. The mean number of teeth present was 13.4 +/- 8.7. The prevalence of
      root surface caries was 89.7%. The mean number of root surfaces with decay or
      fillings and the mean root caries index (RCI) per subject were 3.8 and 25.0%,
      respectively. In both arches, the molars were the most affected by root caries. A
      multiple logistic regression analysis showed that betel chewing (OR = 0.36; 95%
      CI 0.20, 0.65), being >80 years of age (OR = 0.24; CI 0.09, 0.57), number of
      retained teeth (OR = 0.88; CI 0.83, 0.93) and number of root surfaces with
      recession (OR = 1.03; CI 1.01, 1.07) were significantly associated with the
      presence of root surface caries. In conclusion, it was evident from the study
      that the prevalence of root surface caries was high in this group of older
      individuals. Chewing betel, age, number of retained teeth and the number of root
      surfaces with recession emerged as significant predictors of root caries.

PMID- 17556834
TI  - Effect of lesion characteristics and mineralizing solution type on enamel
      remineralization in vitro.
AB  - The aim was to study the effect of lesion preparation technique and solution
      composition on remineralization of artificial lesions in vitro. Lesions were
      prepared with similar total mineral loss, but different mineral distribution,
      i.e., low (14.0) or high R (34.8) values. Lesions from both groups were
      remineralized (10 days, 37 degrees C) in two different solutions, with similar
      supersaturation with respect to hydroxyapatite (St), but calcium:phosphate ratios
      representing either hydroxyapatite stoichiometry or plaque fluid (PF).
      Remineralization was quantified microradiographically, mineral distribution was
      compared with natural white-spot lesions. Mineral loss and depth decreased
      significantly, and surface-zone mineral content (Zmax) increased significantly,
      in all lesions. Overall there was a significant relationship of decreasing
      remineralization with increasing Zmax, but not within either lesion type. PF was
      significantly more efficient than St in high-R lesions, with lesions
      remineralizing almost completely in PF. Remineralization was not significantly
      different in PF or St for low-R lesions but in high-R lesions, PF was more
      efficient than St, possibly through differences in relative saturations with
      respect to different calcium phosphates. Differences in area:solution ratios and
      baseline Zmax values may also have explained the different response to PF. Low-R
      lesions were similar to natural white-spot lesions in terms of mineral
      distribution, whereas high-R were not. Concluding, both lesion and remineralizing
      solution type had a marked influence on remineralization. It is proposed that use
      of low-R lesions would be more appropriate where more physiologically relevant
      mineral distribution is required, whereas high-R lesions would be appropriate for
      studying inherent remineralizing efficiency.

PMID- 17556835
TI  - In vitro evaluation of the effectiveness of acidic fluoride dentifrices.
AB  - This study evaluated the effectiveness of acidic low-fluoride dentifrices
      compared to conventional neutral dentifrices. Enamel blocks were submitted to pH
      cycling and treatment with slurries of dentifrices containing 0, 275, 412, 550
      and 1,100 microg F/g (pH 4.5 or 7.0), and also a commercial dentifrice (1,100
      microg F/g) and a commercial children's dentifrice (500 mug F/g). Variations in
      surface microhardness and in the mineral content in enamel after pH cycling were
      calculated. Enamel blocks treated with acidic dentifrices exhibited less mineral
      loss compared to neutral dentifrices (ANOVA; p < 0.05). The acidic dentifrices
      with 412 and 550 microg F/g had the same effectiveness as the neutral 1,100
      microg F/g dentifrice and commercial 1,100-microg F/g dentifrice.

PMID- 17556836
TI  - Anorexia in hemodialysis patients: the possible role of des-acyl ghrelin.
AB  - BACKGROUND: Anorexia is frequently found in end-stage renal disease and is a
      reliable predictor of morbidity and mortality in hemodialysis (HD) patients. The
      pathogenesis of anorexia is complex and the appetite-modulating hormone ghrelin
      could be involved. Two forms of circulating ghrelin have been described: acylated
      ghrelin (<10% of circulating ghrelin) which promotes food intake, and des-acyl
      ghrelin which induces a negative energy balance. The aim of this cross-sectional
      study is to clarify whether anorexia and body weight change in HD patients relate
      to plasma des-acyl ghrelin levels. METHODS: 34 HD patients and 15 healthy
      controls were studied. The presence of anorexia was assessed by a questionnaire.
      Serum des-acyl ghrelin was measured in HD patients and in 15 body mass index-,
      sex- and age-matched controls by ELISA. Energy intake was assessed by a 3-day
      dietary diary, and fat-free mass (FFM) was evaluated by body impedance analysis.
      Data have been statistically analyzed and are presented as mean +/- SD. RESULTS:
      14 patients (41%) were found to be anorexic, and 20 patients (59%) non-anorexic.
      Energy intake (kcal/day) was significantly lower in anorexic than in non-anorexic
      patients (1,682 +/- 241 vs. 1,972.50 +/- 490; p < 0.05). FFM (%) was lower in
      anorexic than in non-anorexic patients (65.8 +/- 4.4 vs. 70.9 +/- 8.7; p = 0.05).
      Plasma des-acyl ghrelin levels (fmol/ml) were significantly higher in HD patients
      than in controls (214.88 +/- 154.24 vs. 128.93 +/- 51.07; p < 0.05), and in
      anorexic HD patients than in non-anorexic (301.7 +/- 162.4 vs. 159.1 +/- 115.5; p
      < 0.01). CONCLUSION: Anorexia is highly prevalent among HD patients and des-acyl
      ghrelin could be involved in its pathogenesis.

PMID- 17556837
TI  - Early microcirculatory changes after ischemic preconditioning and small bowel
      autotransplantation.
AB  - BACKGROUND/AIMS: Ischemia-reperfusion injury contributes to the high complication
      rate of small bowel transplantation (SBTX). Ischemic preconditioning (IPC)
      protects against reperfusion injury in several organs, but the IPC-induced
      microcirculatory reaction in the intestine is unknown. METHODS: We examined the
      effects of IPC on the macrohemodynamics and graft microcirculation in a canine
      model of SBTX during a 4-hour reperfusion period. In group 1 SBTX was performed,
      in group 2 IPC was induced before graft harvesting (ischemia 3 times for 5 min,
      followed by 10 min of reperfusion). Cardiac index and mesenteric blood flow were
      measured, and the mucosal microcirculation, villus epithelial thickness and
      functional capillary density were monitored by orthogonal polarization spectral
      imaging. Leukocyte-endothelial cell interactions were monitored in the
      postcapillary venules, with intravital fluorescence microscopy. RESULTS:
      Reperfusion decreased cardiac index and mesenteric blood flow during reperfusion;
      IPC significantly improved these changes. Reperfusion was accompanied by
      decreased functional capillary density and epithelial thickness of the villi and
      increased leukocyte-endothelial cell interactions. IPC increased functional
      capillary density, prevented epithelial narrowing and reduced leukocyte rolling
      and adherence. CONCLUSION: IPC improves the macrohemodynamics and the intestinal
      microcirculation and reduces leukocyte-mediated tissue injury during reperfusion.
      IPC can be an effective tool to limit reperfusion injury during SBTX.

PMID- 17556838
TI  - Inhibiting angiogenesis in retinoblastoma.

PMID- 17556839
TI  - Hemoglobin targets versus oxygen delivery: is it time for a new paradigm?

PMID- 17556840
TI  - Minocycline blocks acute bilirubin-induced neurological dysfunction in jaundiced
      Gunn rats.
AB  - BACKGROUND: Extreme hyperbilirubinemia is treated with double volume exchange
      transfusion, which may take hours to commence. A neuroprotective agent that could
      be administered immediately might be clinically useful. Minocycline, an anti
      inflammatory and anti-apoptotic semisynthetic tetracycline, prevents
      hyperbilirubinemia-induced cerebellar hypoplasia in Gunn rats. Acute brainstem
      auditory evoked potential (BAEP) abnormalities occur after giving
      sulfadimethoxine to 16-day-old jaundiced Gunn rats to displace bilirubin into
      tissue including brain. OBJECTIVE: To assess whether minocycline is
      neuroprotective in this model of acute bilirubin encephalopathy. METHODS: We
      recorded BAEPs at baseline and 6 h after injecting sulfadimethoxine. Minocycline
      0.5 mg/kg (n = 4), 5 mg/kg (n = 9), 50 mg/kg (n = 9) or 500 mg/kg (n = 3, all
      died) was administered 15 min before sulfadimethoxine (0 h). Controls received
      saline followed by either sulfadimethoxine (n = 13) or saline (n = 7). RESULTS:
      At 6 h total plasma bilirubin decreased from 10.84 +/- 0.88 mg/dl (mean +/- SD)
      to 0.70 +/- 0.35 mg/dl (p <10(-9)) in all sulfadimethoxine-injected groups. At 6
      h, there was complete protection against decreased amplitudes of BAEP waves II
      and III and increased I-II and I-III interwave intervals (brainstem conduction
      times corresponding to I-III and I-V in humans) with 50 mg/kg minocycline, and
      partial protection with lower doses. CONCLUSIONS: Minocycline 50 mg/kg 15 min
      prior to an intervention that normally produces acute bilirubin neurotoxicity is
      neuroprotective in jaundiced Gunn rat pups. Further studies are needed to
      investigate the temporal course and mechanism of neuroprotection. Minocycline,
      administered immediately, may be clinically useful in treating extreme neonatal
      hyperbilirubinemia and preventing kernicterus. We believe our model provides an
      efficient in vivo model to screen and evaluate new agents that are
      neuroprotective against bilirubin toxicity and kernicterus.

PMID- 17556841
TI  - Hypoxic-ischemic injury in the immature brain--key vascular and cellular players.
AB  - Over the past decade, much has been learned about the cellular and molecular
      mechanisms underlying hypoxic-ischemic (H-I) injury in the preterm human brain.
      The pathogenesis of H-I brain injury is now understood to be multifactorial and
      quite complex, depending on (i) the severity, intensity and timing of asphyxia,
      (ii) selective ischemic vulnerability, (iii) the degree of maturity of the brain,
      and (iv) the characteristics of the ensuing reoxygenation/reperfusion phase. Each
      of these factors has differential effects on the distinct cell populations in the
      brain, with certain specific cell types being particularly vulnerable in the
      developing brain. In this review, we discuss the role of the blood vessels and
      the distinct cell populations, which are the mayor constitutive elements of the
      immature brain, in the pathophysiology of H-I lesion. The presence of fragile and
      poorly anastomosed blood vessels and the existence of disturbances in the blood
      brain barrier alter blood flow, vascular tone and nutrient delivery. Brain cells
      are sensitive to the overstimulation of neurotransmitter receptors, particularly
      glutamate receptors, which can provoke excitotoxicity leading to the death of
      neurons and other cells such as astrocytes and oligodendrocyte progenitors.
      Microglial activation by means of excitatory amino acids and by leukocyte
      migration initiates the inflammatory response giving rise to an increase in
      regional cerebral blood flow and promoting astrocyte and oligodendrocyte
      injuries. A better understanding of these aspects of H-I injury will contribute
      to more efficient strategies for the management of the associated damage.

PMID- 17556842
TI  - The effect of maternal ketanserin treatment on foetal 5-HT receptor function in
      umbilical cord artery of pre-eclamptic patients.
AB  - BACKGROUND: Maternal treatment with the 5-HT(2A) receptor antagonist ketanserin
      (KT) in pre-eclamptic patients is associated with a high placental transmission
      of KT, resulting in pharmacologically active levels of KT in the umbilical cord
      artery (UCA) and the neonate. Prolonged exposure to a 5-HT receptor antagonist
      may influence the functionality of foetal 5-HT receptors and compromise foetal
      development. OBJECTIVE: To study whether exposure to KT influences the
      characteristics of foetal 5-HT receptors, functional studies were performed on 5
      HT(2A) and 5-HT(1B/1D) receptors in UCA from pre-eclamptic patients treated with
      KT. METHODS: UCAs were obtained, immediately after delivery, from pre-eclamptic
      patients (n = 7), treated antenatally with intravenous KT. Pre-eclamptic patients
      (n = 13), not treated with KT (non-KT), were included as a control group.
      Segments of UCA were prepared and mounted in tissue baths and isometric force
      changes were determined. Cumulative concentration response curves to 5-HT and to
      the 5-HT(1B/1D )receptor agonist sumatriptan were constructed in the absence or
      presence of the 5-HT(2A) receptor antagonist KT or the 5-HT(1B/1D) receptor
      antagonist GR125743, respectively. RESULTS: All UCA segments showed contractile
      responses to both 5-HT and sumatriptan, and the concentration response curves
      showed a rightward shift with increasing concentrations of KT and GR125743,
      respectively, indicating the presence of functional 5-HT(2A) and 5-HT(1B/1D)
      receptors in the foetal tissue. No significant differences were found in maximum
      response (E(max))(expressed in percent of response on 100 mM KCl) or potency
      (pEC(50)) of 5-HT in both groups (E(max) = 141 +/- 7.7%, pEC(50) = 7.67 +/- 0.26
      in KT-treated group and E(max) = 162 +/- 12.6%, pEC(50) = 7.69 +/- 0.14 in non-KT
      treated group, respectively). No significant differences were found in the
      potency of the antagonist KT in both study groups (pK(b) = 7.65 +/- 0.31 in KT
      group and 7.46 +/- 0.17 in non-KT group, respectively). Similarly, with
      sumatriptan, no significant differences were found between KT-treated patients
      and non-KT treated patients (E(max) = 142 +/- 16.2 and 140 +/- 14.7%,
      respectively, pEC(50) = 6.17 +/- 0.37 and 6.41 +/- 0.28 respectively, pK(b) of
      GR125743 = 7.83 +/- 0.48 and 8.43 +/- 0.29, respectively). CONCLUSION: Foetal
      exposure to KT in pre-eclamptic patients does not seem to influence the
      functional characteristics of 5-HT(2A) and 5-HT(1B/1D) receptors in the UCA.

PMID- 17556843
TI  - NMDA channel antagonist MK-801 does not protect against bilirubin neurotoxicity.
AB  - BACKGROUND: Bilirubin encephalopathy or kernicterus is a potentially serious
      complication of neonatal hyperbilirubinemia. The mechanism of bilirubin-induced
      neurotoxicity is not known. Many neurological insults are mediated through NMDA
      receptor activation. OBJECTIVE: We assessed the effect of the NMDA channel
      antagonist, MK-801 on bilirubin neurotoxicity in vivo and in vitro. METHODS:
      Bilirubin toxicity in vitro was assessed using trypan blue staining.
      Sulfadimethoxine injected (i.p.) jaundiced Gunn rat pups exhibit many
      neurological sequelae observed in human hyperbilirubinemia. Brainstem auditory
      evoked potentials (BAEPs), a noninvasive sensitive tool to assess auditory
      dysfunction due to bilirubin neurotoxicity, were used to assess neuroprotection
      with MK-801 (i.p.) in vivo. RESULTS: In primary cultures of hippocampal neurons,
      20 min exposure to 64:32 microM bilirubin:human serum albumin reduced the cell
      viability by approximately 50% ten hours later. MK-801 treatment did not protect
      the cells. MK-801 pretreatment doses ranging from 0.1-4.0 mg/kg did not protect
      against BAEP abnormalities in Gunn rat pups 6 h after sulfadimethoxine injection.
      CONCLUSION: Our findings suggest that bilirubin neurotoxicity is not mediated
      through NMDA receptor activation.

PMID- 17556844
TI  - Bruising at birth: antenatal associations and neonatal outcome of extremely low
      birth weight infants.
AB  - BACKGROUND: Early studies have identified severe cranial bruising as a risk
      factor for intraventricular hemorrhage (IVH) in premature infants but the nature
      of this association has not been evaluated. OBJECTIVE: To identify antenatal
      predictors and associations with neonatal outcome of bruised extremely low birth
      weight infants. METHODS: A cohort study comparing 34 bruised and 116 non-bruised
      infants (birth weight <or=1,000 g), delivered in two 'Hadassah' university
      hospitals in Jerusalem between 2000 and 2004. Bruised patients were divided
      according to the severity of bruising. A univariate model was first applied to
      examine the associations of the individual independent variables with the outcome
      variable, followed with a logistic stepwise regression model, performed for each
      of the outcome variables. RESULTS: In a stepwise logistic regression on 'Any
      bruising' and 'Severe bruising', only increasing gestational age and exposure to
      antenatal steroids prior to delivery maintained a protective association with
      bruising (OR = 0.74; 95% CI: 0.58-0.94; p = 0.015, OR = 0.38; 95% CI: 0.16-0.90;
      p = 0.028, respectively, for 'Any bruising', and OR = 0.77; 95% CI: 0.59-1.01; p
      = 0.055, OR = 0.29; 95% CI: 0.12-0.73; p = 0.008, respectively, for 'Severe
      bruising'). In a stepwise logistic regression analysis, with 'Any bruising' and
      'Severe bruising' as forced-in variables and controlling for gestational age,
      small for gestational age, Apgar scores, respiratory distress syndrome and
      pneumothorax, 'Severe bruising', but not 'Any bruising', was found to be
      associated significantly with severe IVH (OR = 5.60; 95% CI: 1.86-16.82; p =
      0.002), whereas both 'Any bruising' and 'Severe bruising' were significantly
      associated with mortality (OR = 6.31; 95% CI: 2.37-16.83; p = 0.000, OR = 3.33;
      95% CI: 1.16-9.52; p = 0.025 respectively). CONCLUSION: Antenatal exposure to
      steroids and increasing gestational age are associated with a lower incidence of
      bruising at birth in extremely low birth weight infants. Severe bruising at birth
      is associated with increased incidence of severe intraventricular hemorrhage and
      mortality.

PMID- 17556845
TI  - Red cell folate and plasma homocysteine in preterm infants.
AB  - BACKGROUND: The supplementation of preterm infants with folic acid is routine
      practice in many neonatal units. However, the advent of preterm formula milks and
      breast milk fortifiers have increased folic acid intake. We measured red cell
      folate in preterm infants who received preterm formula milks and breast milk
      fortifiers to determine whether additional folic acid supplementation was still
      required. A potential benefit of folic acid supplementation is reduction of
      plasma total homocysteine (tHcy). tHcy appears to have a linear association with
      the risk of atherothrombotic vascular events in adults but its role in
      intraventricular haemorrhage and associated white matter damage in preterm
      infants is not known. As there is little information regarding tHcy in preterm
      infants, we also measured tHcy in this study. METHODS: Red cell folate and tHcy
      were measured at 1 and 4 weeks of age and before discharge in 28 consecutive
      infants <34 weeks' gestation. Factors which may have affected folate and
      homocysteine status were recorded. RESULTS: Red cell folate ranged between 266
      and 1,513 ng/ml and deficiency (<140 ng/ml) was not observed in any sample. Red
      cell folate concentration tended to increase with increasing age. tHcy ranged
      from 0.8 to 12.2 micromol/l and fell within the 'normal' range for fasting
      adults. CONCLUSIONS: Preterm formula milks and breast milk fortifiers provide
      sufficient folic acid to prevent folate deficiency in preterm infants. Although
      tHcy fell within the 'normal' range for fasting adults, more research is needed
      to determine optimal concentration of tHcy for preterm infants.

PMID- 17556846
TI  - Prolactin response to formalin is related to the acute nociceptive response and
      it is attenuated by combined application of different stressors.
AB  - Subcutaneous injection of diluted formalin (0.2 ml of 4% solution/100 g BW) can
      influence the increase of plasma epinephrine levels in rats exposed to
      exteroceptive (handling, immobilization), as well as to interoceptive stressors
      (insulin-induced hypoglycemia), without having any effect on norepinephrine
      release. In the present studies, the effect of the above-mentioned stressors has
      been investigated on formalin-induced prolactin (PRL) and corticosterone
      secretion. Administrations of formalin via chronically implanted subcutaneous
      cannula into the hind limb without handling induce an immediate increase in both
      plasma PRL and corticosterone levels. While PRL concentration reaches its peak
      value within 5 min then returns to the basal level by the end of the 30th min,
      corticosterone level also starts to rise immediately after formalin
      administration reaching its highest concentration within 15-30 min, but it
      remains at this high level during the next 60 min, then it declines and returns
      to the pre-injection level. Application of formalin to animals exposed to
      different heterotypic stressors (like handling or insulin-induced hypoglycemia)
      produces an attenuated PRL response, while plasma corticosterone levels induced
      by the same nociceptive component remained unchanged. Combinations of formalin
      injection with immobilization also show an attenuated PRL response. The present
      data indicate that plasma PRL response to formalin is related to its acute
      nociceptive phase, and application of different stressors prior to formalin
      injection significantly attenuate plasma PRL levels, while it does not influence
      corticosterone responses.

PMID- 17556847
TI  - Brain-derived neurotrophic factor and its intracellular signaling pathways in
      cocaine addiction.
AB  - Cocaine addiction is one of the severest health problems faced by western
      countries, where there is an increasing prevalence of lifelong abuse. The most
      challenging aspects in the treatment of cocaine addiction are craving and
      relapse, especially in view of the fact that, at present, there is a lack of
      effective pharmacological treatment for the disorder. What is required are new
      pharmacological approaches based on our current understanding of the
      neurobiological bases of drug addiction. Within the context of the behavioral and
      neurochemical actions of cocaine, this paper considers the contribution of brain
      derived neurotrophic factor (BDNF) and its main intracellular signaling
      mechanisms, including mitogen-activated protein kinase/extracellular signal
      regulated protein kinase (MAPK/ERK) and phosphatidylinositol 3-kinase (PI3K), in
      psychostimulant addiction. Repeated cocaine administration leads to an increase
      in BDNF levels and enhanced activity in the intracellular pathways (PI3K and
      MAPK/ERK) in the reward-related brain areas, which applies especially several
      days following withdrawal. It has been hypothesized that these neurochemical
      changes contribute to the enduring synaptic plasticity that underlies sensitized
      responses to psychostimulants and drug-conditioned memories leading to compulsive
      drug use and frequent relapse after withdrawal. Nevertheless, increased BDNF
      levels could also have a role as a protection factor in addiction. The inhibition
      of the intracellular pathways, ERK and PI3K, leads to a disruption in sensitized
      responses and conditioned memories associated with cocaine addiction and suggests
      new, potential therapeutic strategies to explore in the dependence on
      psychostimulants.

PMID- 17556848
TI  - Familial risk for depression and p3b component as a possible neurocognitive
      vulnerability marker.
AB  - OBJECTIVE: Complex genetic mechanisms are involved in the vulnerability to
      depressive disorders and cognitive dysfunctions found in depression. This study
      was performed to explore the effect of the familial risk for depression on
      electrophysiological correlates of attentional functions as demonstrated by an
      event-related potential (ERP) go/no-go experiment. METHODS: The component P3b as
      an indicator of target detection processing was investigated in two groups of
      healthy subjects with or without a family history of depression (n = 14 each). An
      electrophysiological source localization method (LORETA) was employed to allow a
      neuro-anatomical interpretation for the ERP data. RESULTS: The group with a
      familial risk for depression showed a reduced P3b amplitude over left temporal
      areas in contrast to the control group. This two-dimensional effect was
      associated with a significantly reduced activation of the left middle temporal
      gyrus. CONCLUSIONS: The P3b amplitude decrement might represent a neurocognitive
      vulnerability marker for the development of depression.

PMID- 17556849
TI  - Enhanced suppression of adrenocorticotropic hormone and cortisol responses to
      hypothalamic-pituitary-adrenal function and thyrotropin-releasing hormone tests
      after stressful life events in patients with major depressive disorder.
AB  - BACKGROUND: It is commonly believed that there exists a relationship between the
      outcome of thyrotropin-releasing hormone (TRH) test, the combined
      dexamethasone/corticotropin-releasing hormone (DEX/CRH) test and stressful life
      events (SLEs) in major depressive disorder. OBJECTIVE: SLEs influence the TRH and
      DEX/CRH tests in major depressive disorder when administered at the time of
      admission and improvement. METHODS: The TRH and DEX/CRH tests were administered
      to patients hospitalized for major depressive disorders - on the 4th through the
      7th hospital day and at the time of improvement. We measured DeltaMAX TSH,
      DeltaMAX ACTH, ACTH AUC, DeltaMAX cortisol, cortisol AUC, DeltaMAX ACTH/DeltaMAX
      TSH and DeltaMAX cortisol/DeltaMAX TSH. RESULTS: SLEs were significantly
      negatively associated with DeltaMAX ACTH, ACTH AUC and cortisol AUC at the time
      of admission. However, these relationships lost significance at the time of
      improvement. The sample (41 patients at the time of admission, 18 patients at the
      time of improvement) was relatively small, which may have contributed to false
      negative results. CONCLUSION: SLEs may be negatively associated with the outcome
      of the DEX/CRH tests in major depressive disorder. The hypothalamic-pituitary
      adrenal axis in the DEX/CRH test was modulated by SLEs.

PMID- 17556850
TI  - Changes in the hypothalamic-pituitary-adrenal axis and leptin levels during
      antidepressant treatment.
AB  - BACKGROUND: In depressed patients, overstimulation of the hypothalamo-pituitary
      adrenocortical (HPA) system, probably caused by glucocorticoid receptor
      resistance, is the most consistent neurobiological finding. Glucocorticoids
      themselves are reported to increase leptin synthesis and secretion in humans.
      METHODS: We examined alterations in plasma levels of leptin as well as changes in
      the HPA system function using the combined dexamethasone/corticotropin-releasing
      hormone (dex/CRH) test on admission and at discharge in 74 depressed inpatients.
      RESULTS: Mean leptin concentration did not change significantly between admission
      and discharge. However, changes in ACTH response and partial cortisol response to
      the combined dex/CRH test between admission and discharge were significantly
      correlated with leptin levels at discharge. CONCLUSIONS: Leptin levels at
      discharge rise as the HPA axis normalizes. These findings may be explained by an
      improvement in glucocorticoid receptor sensitivity among depressed patients
      during antidepressant therapy and a consecutively increased influence of
      glucocorticoids on leptin levels via the glucocorticoid receptor.

PMID- 17556851
TI  - Sleep in major depression: relation to memory performance and outcome after
      interpersonal psychotherapy.
AB  - BACKGROUND: Earlier findings suggest both a link between sleep and memory
      consolidation and a relationship between abnormal sleep at baseline and poor
      treatment outcome in major depression after interpersonal psychotherapy (IPT).
      METHODS: Pre-treatment polysomnography was examined in 32 patients with a major
      depressive episode (mean age = 39.5 years, 20 women). Declarative memory was
      tested by the Rey-Osterrieth Complex Figure Test and a paired associative word
      list and procedural learning was assessed by a mirror tracing skill. All patients
      were treated with IPT according to the manual and did not receive any
      antidepressant medication. Twenty-three patients took part in a minimum of 12
      sessions of IPT. Remission was defined as 2 consecutive weeks with a score <8 on
      the Hamilton Rating Scale of Depression. RESULTS: Declarative visual memory
      performance was associated with total sleep time and total amount of rapid eye
      movement sleep. In IPT remitters (n = 14), there was a trend towards a decrease
      in rapid eye movement density (first period) and a significant decrease in delta
      power in pre-treatment sleep in comparison to non-remitters (n = 9). Treatment
      outcome after IPT was also associated with declarative memory performance at
      baseline (as a trend). CONCLUSIONS: Further indications of a role of sleep in
      memory processes and of the importance of specific sleep parameters as markers
      for a positive treatment response to psychotherapy were found.

PMID- 17556852
TI  - Olanzapine increases grey and white matter volumes in the caudate nucleus of
      patients with schizophrenia.
AB  - There are inconsistent reports regarding the caudate nucleus volume in patients
      with schizophrenia compared with healthy subjects. The reason for this is that
      neuroleptic medication may affect the volume of the caudate nucleus in
      schizophrenic patients. To clarify which antipsychotic medication changes the
      volume of the caudate nucleus in patients with schizophrenia, we measured the
      volumes of grey and white matter in the caudate nucleus of schizophrenic
      patients. Ten patients with schizophrenia were examined twice by magnetic
      resonance imaging (MRI) to measure the grey and white matter volumes in the
      caudate nucleus. After the first MRI examination, all the patients were treated
      with olanzapine. The clinical responses were evaluated by the positive and
      negative rating scale. When the symptoms improved, the patients were examined by
      a second MRI scan. Ten healthy control subjects also underwent MRI. The
      schizophrenic patients had reduced volumes of grey and white matter in the
      caudate nucleus compared to the healthy control subjects. The volumes of grey and
      white matter in the caudate nucleus of the schizophrenic patients increased after
      treatment with olanzapine. These findings suggest that treatment with olanzapine
      may increase the grey and white matter volumes in the caudate nucleus in patients
      with schizophrenia.

PMID- 17556853
TI  - No association between dopamine D4 receptor gene -521 C/T polymorphism and
      tardive dyskinesia in schizophrenia.
AB  - Tardive dyskinesia (TD) is a long-term adverse effect of antipsychotics. We
      evaluated whether a candidate functional polymorphism of the dopamine D4 receptor
      (DRD4) gene is associated with drug-induced TD in 209 Korean schizophrenic
      patients with TD (n = 83) and without TD (n = 126) who were matched for
      antipsychotic drug exposure and other relevant variables. There was no
      significant association of the genotype and allele frequencies determined by the 
      521 C/T SNP of DRD4 between TD and non-TD patients. In addition, there was no
      significant difference in terms of total Abnormal Involuntary Movement Scale
      scores among the 3 genotype groups. Within the limitations imposed by the size of
      the clinical sample, these findings suggest that the DRD4 -521 C/T SNP does not
      contribute significantly to the risk for TD.

PMID- 17556854
TI  - The degenerative dysarthrias: a window into critical clinical and research
      issues.
AB  - Although diversity of symptoms and urgency of needs pose many challenges,
      management of the degenerative dysarthrias is a crucial aspect of clinical
      practice. The purpose of this article is to review current research literature on
      selected degenerative dysarthrias including those associated with Parkinson's
      disease, multiple sclerosis, and amyotrophic lateral sclerosis. These dysarthrias
      are prevalent yet represent distinct patterns of underlying neuropathology,
      symptoms, age of onset, and rate of progression. Literature searches including
      the period 1997-2006 yielded 148 different studies reporting data on
      communication issues related to dysarthria. By far the largest category of
      studies was that which provided a basic description of speech production
      including the neurophysiologic, acoustic, or perceptual properties of dysarthria.
      Other categories included management (assessment and treatment) and the
      psychosocial consequences of dysarthria. While the topic of management of
      degenerative dysarthria is a focused one, it provides a window into many issues
      critical to the field of communication disorders including fundamental properties
      of speech production, development of evidence-based treatment techniques, the
      staging of these techniques into an effective management sequence, and the
      psychosocial consequences of communication disorders along with techniques to
      maintain communicative participation in the face of degenerative conditions.

PMID- 17556855
TI  - Evidence-based practice and speech-language pathology: strengths, weaknesses,
      opportunities and threats.
AB  - Speech-language pathologists are increasingly required to demonstrate that their
      practice is based on evidence. While the concept of evidence-based practice has
      strengths, there have been some weaknesses in its application in speech-language
      pathology. Nevertheless, since current health care demands compliance, the
      profession must consider the opportunities and threats that evidence-based
      practice poses. This paper reviews the literature to provide an understanding of
      the relevance of evidence-based practice for speech-language pathology. It
      considers the assumptions on which definitions of evidenced-based practice rely
      and reviews the ways in which clinicians might base their practice on evidence.
      While the medical model of evidence-based practice research is controversial even
      in the medical field, the concept provides opportunities for the profession of
      speech-language pathology. Evidence-based practice has the potential to improve
      intervention for people with communication disorders, increase resources for
      services and enhance perception of the profession.

PMID- 17556856
TI  - Molecular windows into speech and language disorders.
AB  - Why do some children fail to acquire speech and language skills despite adequate
      environmental input and overtly normal neurological and anatomical development?
      It has been suspected for several decades, based on indirect evidence, that the
      human genome might hold some answers to this enigma. These suspicions have
      recently received dramatic confirmation with the discovery of specific genetic
      changes which appear sufficient to derail speech and language development.
      Indeed, researchers are already using information from genetic studies to aid
      early diagnosis and to shed light on the neural pathways that are perturbed in
      these inherited forms of speech and language disorder. Thus, we have entered an
      exciting era for dissecting the neural bases of human communication, one which
      takes genes and molecules as a starting point. In the current article I explain
      how this recent paradigm shift has occurred and describe the new vistas that have
      opened up. I demonstrate ways of bridging the gaps between molecules, neurons and
      the brain, which will provide a new understanding of the aetiology of speech and
      language impairments.

PMID- 17556857
TI  - Present-day importance of the velocardiofacial syndrome. To commemorate the late
      prof. Eva sedlackova, MD, on the 50th anniversary of her original publication.
AB  - In the year 1955, Sedlackova described a syndrome of congenitally shortened velum
      accompanied by hypernasal speech, facial dysmorphisms and further anomalies, as
      well as mental retardation. In the following years, she also reported on cardiac
      malformations and submucous clefts. In 1978, Shprintzen's group published a very
      similar pattern apart from overt clefts, coined it as velocardiofacial syndrome
      (VCFS) and explained it in 1992 by microdeletion 22q11.2. Between 1996 and 2001,
      Vrticka and colleagues demonstrated del 22q11.2 in 16 of 20 cases classified as
      Sedlackova syndrome. Thus, the common etiology and the identity of Sedlackova
      syndrome with Shprintzen syndrome were proven. Our findings of frequent
      cardiovascular malformations, of prevailing mental retardation and of several
      late-onset psychoses emphasize the necessity of genetic testing in all
      individuals suspected of VCFS. In del 22q11.2-proven cases, we recommend genetic
      counseling because of the risk of more severe expression of the VCFS symptoms in
      subsequent generations. Recently, several authors repeatedly stressed the
      importance of VCFS by pointing out the associated cardiac and laryngeal
      malformations and by warning against the risk of innate carotid medialization in
      velopharyngeal surgery, by evoking linked otological problems, by elucidating the
      accompanying immune and hormonal dysfunctions, by summarizing the voice and
      resonance disorders as well as by discussing the difficulties in rehabilitation
      due to mental, language and speech retardation in VCFS subjects. Because of its
      multiple impact, the clinical pattern of VCFS due to del 22q11.2 remains a
      persistent and important present-day diagnostic and therapeutic challenge.

PMID- 17556858
TI  - Effects of place of articulation and aspiration on voice onset time in Mandarin
      esophageal speech.
AB  - The ability of Mandarin esophageal speakers to distinguish between aspirated and
      unaspirated stops, and to distinguish between different places of articulation of
      stops were examined. Aspirated and unaspirated voiceless stops produced by normal
      laryngeal (NL) and standard esophageal (SE) speakers were studied. VOT values of
      the five different stops (/p(h), t(h), k(h), p, t/) of Mandarin followed by the
      vowel /a/ produced by NL and SE speakers were compared. Results from the
      perceptual experiment indicated that, while voiceless unaspirated stops produced
      by SE speakers were not signaled with a high level of accuracy, voiceless
      aspirated stops were perceived correctly by the listeners. Acoustic analysis
      showed that SE speakers consistently produced shorter VOT than NL speakers. Velar
      stops were associated with significantly longer VOT values than bilabial and
      alveolar stops in NL speakers. It was also found that, with the use of the PE
      segment, SE speakers were still able to use VOT to distinguish between aspirated
      and unaspirated stops, but they were unable to distinguish between bilabial,
      alveolar, and velar places of articulation.

PMID- 17556859
TI  - Ghrelin reduces hepatic mitochondrial fatty acid beta oxidation.
AB  - Ghrelin is a 28-amino-acid peptide secreted during starvation by gastric cells.
      Ghrelin physiologically induces food intake and seems to alter lipid and glucid
      metabolism in several tissues such as adipose tissue and liver. Liver has a key
      position in lipid metabolism as it allows the metabolic orientation of fatty
      acids between oxidation and esterification. We investigated the effects of
      peripheral ghrelin administration on 2 crucial parameters of fatty acid
      oxidation: the levocarnitine (L-carnitine)-dependent entry of the fatty acids in
      the mitochondria and the mitochondrial fatty acid oxidation. Ghrelin was either
      given to rats prior to the hepatocyte preparation and culture or used to treat
      hepatocytes prepared from control animals. Direct incubation of ghrelin to raw
      hepatocytes did not induce any change in the studied parameters. In hepatocytes
      prepared from 3 nmol ghrelin-treated rats, a 44% reduction of the mitochondrial
      fatty acid oxidation while no alteration of the L-carnitine-related parameters
      were observed. These results suggested (a) that ghrelin has no direct effect on
      liver, and (b) that when administrated to a whole organism, ghrelin may alter the
      lipid metabolism and the energy balance through a marked decrease in liver fatty
      acid oxidation.

PMID- 17556860
TI  - Pituitary imaging abnormalities in patients with and without hypopituitarism
      after traumatic brain injury.
AB  - Recent evidence suggests that patients with traumatic brain injury (TBI) are at
      substantial risk of hypopituitarism. The pathomechanisms, however, are not
      completely understood yet. Little is known about the association of morphological
      changes in the sella region with pituitary function in TBI. In this study, we
      assessed morphological abnormalities of the sella region in patients with TBI and
      their relation to endocrine function. We studied magnetic resonance (MR) or
      computed tomography (CT) scans of 22 patients with TBI [17 men, 5 women, age
      (mean+/-SD) 43.5+/-10.6 yr, time after trauma 17.4 +/-15.0 yr]. Of these, 15
      patients had some degree of hypopituitarism. We found abnormalities of the sella
      region in 80% of the patients with hypopituitarism and 29% of those without
      hypopituitarism (Fisher's exact test, p=0.032). The most common abnormality was
      loss of volume or empty sella, followed by native signal inhomogeneities,
      perfusion deficit, and lack of neurohypophyseal signal. Our results indicate that
      pituitary imaging abnormalities are more common in TBI patients with
      hypopituitarism than those without. Both immediate trauma-induced pathology as
      necrosis and hemorrhage as well as multifactorial mid- to long-term changes may
      underlie these abnormalities.

PMID- 17556861
TI  - Acquired prolactin deficiency in patients with disorders of the hypothalamic
      pituitary axis.
AB  - Acquired PRL deficiency occurs when the anterior pituitary is functionally
      destroyed, and it usually accompanies other pituitary hormone deficiencies. We
      retrospectively investigated in an outpatient endocrine clinic of a major
      tertiary medical center the prevalence and clinical characteristics of acquired
      PRL deficiency in patients with diseases of the hypothalamic-pituitary axis. The
      study included 100 consecutive patients, 61 men and 39 women, aged 4-79 yr at
      diagnosis. Patients were divided by PRL level to normal (>5 ng/ml), mild (3-5
      ng/ml), and severe deficiency (<3 ng/ml). Twenty-seven patients (27%) had PRL
      deficiency, 13 mild deficiency and 14 severe deficiency. Patients with severe PRL
      deficiency tend to be younger at diagnosis (mean age, 37.5+/-21.8 yr) than
      patients with normal PRL (46+/-18.5 yr; ns). Underlying diseases including
      pituitary apoplexy, non-functioning pituitary adenoma, craniopharyngioma, and
      idiopathic hypogonadotropic hypogonadism were associated with PRL deficiency. The
      incidence of severe PRL deficiency rose with an increase in the number of other
      pituitary hormone deficits (ACTH, TSH, gonadotropin, vasopressin), from 0 in
      patients with no other deficits to 38% in patients with 4 deficits (p=0.006).
      Patients with severe deficiency had a mean of 3 hormone deficits compared to 1.8
      in the other groups (p=0.006). PRL deficiency was significantly associated with
      TSH, ACTH and GH deficiency. CONCLUSIONS: PRL deficiency is common in patients
      with hypothalamic-pituitary disorders, especially pituitary apoplexy and
      craniopharyngioma. Acquired severe PRL deficiency can be considered a marker for
      extensive pituitary damage and a more severe degree of hypopituitarism.

PMID- 17556862
TI  - Urinary iodine excretion and antiperoxidase enzyme antibody in goitrous and
      healthy primary school children of Arak, Iran.
AB  - OBJECTIVE: To determine urinary iodine excretion (UIE) and antiperoxidase enzyme
      antibody (anti-TPO Ab) in primary school-age children living in Arak, Iran, in
      2005, after 10 yr of iodized salt distribution in an effort to ameliorate iodine
      deficiency. METHODS: Through an observational, case-control study and by means of
      satisfied sampling, 6520 primary school children were examined for goiter, and
      then 193 goiterous children (case) and 151 healthy (control) children were
      assessed as representative samples for thyroid function tests, antiperoxidase
      antibody, and urinary iodine excretion. Normal values of anti-TPO Ab were <40
      U/ml and high values >75 U/ml. Normal values of urinary iodine concentration were
      > or =10.0 microg/dl, and severe iodine deficiency were <2 microg/dl. The data
      were analyzed and compared by the Chi- Square tests and Mann-Whitney U in SPSS
      software; p-values <0.05 were considered statistically significant. RESULTS:
      Total mean prevalence of goiter was 5.2%, ranging from 3.6 to 6.4% in different
      schools. The prevalence of goiter increased with age; it was 3% in children aged
      6-7 yr and 6.3% in children aged 11 yr (p<0.001). Mean iodine urinary
      concentration was 16.36 microg/dl (+/-1.58). No difference was seen between the
      mean urinary iodine in girls (17.30+/-3.80 micorg/dl) and boys (15.72+/-2.72
      microg/dl). No difference was seen between the mean urinary iodine in goiterous
      and healthy school children (17.4+/-3.7 microg/dl vs 15.3+/-3.18 microg/dl,
      p=0.78). About 49.5% of school children had UIE<10 microg/dl and 28% had UIE<5
      microg/dl. High levels of anti-TPO Ab were found in 21 school children (18
      goiterous vs 3 healthy children, p=0.01) resulting in a total prevalence of 6.1%.
      In females, the prevalence was 1.3 times higher than in males (male:female ratio
      3/4). Thirteen out of 21 (62%) children with positive antibodies had significant
      goiter (grade 2), and 5 (24%) had small goiter (grade 1), whereas only 3 children
      (14%) had normal thyroid size (p=0.001). CONCLUSION: If urinary iodine
      concentration is considered an index of total body iodine content, this study
      demonstrated that prolonged iodized salt intake has minimized the occurrence of
      iodine deficiency goiter and now autoimmune thyroid enlargement is one cause for
      continuous goiter in primary school children, although there are unknown
      etiologies that need to be considered in further studies.

PMID- 17556863
TI  - Ras homolog enriched in striatum inhibits the functional activity of wild type
      thyrotropin, follicle-stimulating hormone, luteinizing hormone receptors and
      activating thyrotropin receptor mutations by altering their expression in COS-7
      cells.
AB  - Ras homolog enriched in striatum (Rhes) is a member of the Ras family of small
      GTPases detected in the thyroid. Rhes inhibits signal transduction from Galphas
      protein. In this study we investigated whether Rhes can interfere with
      stimulation of cAMP/protein kinase A (PKA) pathway of TSH, FSH and LH receptors
      (TSHr, FSHr, LHr) and of activated TSHr mutants. Receptors were transiently
      transfected in COS-7 cells with or without Rhes; cAMP was evaluated in basal
      conditions and after hormone stimulation. Constitutive and bovine TSH (bTSH)
      stimulated activity of wild type (wt) and mutated TSHr was inhibited after Rhes
      co-transfection. Rhes decreased cAMP after FSH and hCG beta-subunit (betahCG)
      stimulation in cells expressing the cognate receptors. In binding experiments
      Rhes, as another membrane protein, sodium/iodide symporter (NIS), reduced
      membrane expression of wt TSHr (wtTSHr). In conclusion, Rhes can interfere with
      the functional activity of wt and mutated TSHr and with the respective hormone
      stimulated cAMP production of FSHr and LHr. This interference is not specific and
      due to the co-expression of two membrane proteins.

PMID- 17556864
TI  - Familial pericentric inversion chromosome 3 and R448C mutation of CYP11B1 gene in
      Turkish kindred with 11beta-hydroxylase deficiency.
AB  - 11beta-hydroxylase deficiency is the second most common cause of congenital
      adrenal hyperplasia (CAH). This isoenzyme is coded by two highly homologous genes
      of cytochrome P450: CYP11B1 and CYP11B2 which were mapped to the chromosomal band
      8q24. The aim of this study was to perform a series of molecular and cytogenetic
      analyses in two families with 11beta-hydroxylase deficiency of the Turkish
      kindred. Mutational analysis was carried out by directly sequencing the PCR
      products of CYP11B1 gene. We performed fluorescence in situ hybridisation (FISH)
      experiments with consecutive bacterial artificial chromosome (BAC) clones to map
      the breakpoints of the inversion of chromosome 3 which was detected during the
      karyotypic analysis of the propositus. Homozygous R448C mutations were detected
      in 2 individuals with 11beta-hydroxylase deficiency. Interestingly, karyotypic
      change of pericentric inversion [inv(3)(p13q24)] was detected in both individuals
      who are cousins, one transmitted paternally and the other maternally. The
      breakpoint at 3p included one interesting gene PPP4R2. Here we present the data
      of two Turkish families' members having 11beta-hydroxylase deficiency coupled
      with the familial chromosomal aberration of inv(3)(p13q24). Our data suggest that
      codon 448, which is a mutational hot spot in CYP11B1 causing 11beta-hydroxylase
      deficiency, is not restricted to Jews of Moroccan origin. Phenotypic variations
      observed in former studies in patients homozygous for R448H were stated to be due
      to other factors outside the CYP11B1 locus. The breakpoint in 3p might be a
      candidate region affecting variations in phenotypes of 11beta-hydroxylase
      deficiency.

PMID- 17556865
TI  - Pioglitazone has anti-inflammatory effects in patients with Type 2 diabetes.
AB  - BACKGROUND: Type 2 diabetes is characterized by increased acute phase serum
      proteins. They are also risk factors for cardiovascular disease. We wanted to
      study how improvement of glycemic control with pioglitazone or glibenclamide
      affects their serum concentrations. MATERIALS AND METHODS: A total of 59 patients
      with Type 2 diabetes (age 57.3+/-1.2 yr, glycosylated hemoglobin (HbA1c) 8.3+/
      0.7%, body mass index (BMI) 31.4+/-0.8 kg/m2) participated in the study. They
      were previously treated either with diet alone or in combination with one oral
      antihyperglycemic medicine. After a 1-week lead-in period on diet only, the
      patients were randomized to pioglitazone or glibenclamide. Blood samples for
      alpha-1-acid glycoprotein (A1GP), Creactive protein (CR P) and serum amyloid A
      (SAA) were taken before the treatments and during the therapy after 20 and 52
      weeks. RESULTS: Baseline A1GP correlated with CR P (r=0.70, p<0.001) and fasting
      glucose (r=0.32, p<0.02). Baseline CR P correlated with HbA1c (r=0.26, p<0.05)
      and insulin (r=0.37, p<0.01). The anti-hyperglycemic effect was comparable with
      HbA1c levels decreasing both in the pioglitazone (from 8.18+/-0.09% to 7.63+/
      0.17%, p<0.01) and glibenclamide (from 8.35+/-0.12% to 7.77+/-0.16%, p<0.01)
      groups. Pioglitazone treatment was associated with a reduction in A1GP at 20
      weeks (p<0.001) and at 52 weeks (p<0.05) as compared to baseline. The
      significance remained also after comparison to glibenclamide therapy (p<0.001 and
      p<0.05, 20 and 52 weeks respectively). CR P was also more reduced in the
      pioglitazone group at 20 weeks of treatment (p<0.05). CONCLUSIONS: Inflammatory
      factors and markers of hyperglycemia are associated in patients with Type 2
      diabetes. Pioglitazone treatment results in reduced A1GP concentration suggesting
      an anti-inflammatory effect.

PMID- 17556866
TI  - Ghrelin improves growth hormone responses to growth hormone-releasing hormone in
      a streptozotocin-diabetic model of delayed onset.
AB  - GH secretion is markedly altered in diabetes mellitus (DM) in both rats and
      humans, albeit in opposite directions. In the rat, diabetes suppresses pulsatile
      GH secretion, especially high amplitude pulses, and decreases GH responses to
      secretagogue, depending inversely on severity of metabolic alteration. In the
      present study, we wanted to address the GH responses to GHRH and low doses of
      ghrelin in a streptozotocin (STZ) model of diabetes characterized by the delayed
      onset of the metabolic alterations. We have shown that the administration of high
      doses of STZ (90 mg/kg in 0.01 M solution of chloride-sodium, ip) to five-day-old
      pups (n5-STZ) can induce the appearance of a characteristic diabetic syndrome in
      adult age, the diabetic triad, with elevated plasma glucose levels: polyuria,
      polydipsia, hyperphagia, and reduced body weight gain. At the age of 3 months, in
      these n5-STZ male and female rats the GH responses to GHRH (1 microg/kg) and GHRH
      combined with ghrelin (1+3 microg/kg) had diminished both in punctual times and
      in the area under the curve (AUC). However, the combined administration of GHRH
      and ghrelin, being the more potent stimulus, elicited a synergistic GH response.
      Thus, male and female rats with delayed onset diabetes displayed an altered GH
      response to GHRH, although the combined administration of GHRH and ghrelin was
      able to restore the GH secretion with a synergistic effect.

PMID- 17556867
TI  - Association of insulin resistance and nocturnal fall of blood pressure in GH
      deficient adults during GH replacement.
AB  - The GH deficiency syndrome in adults is characterized by changes in body
      composition, metabolic, cardiovascular and psychological profile. Such
      alterations fit the metabolic syndrome. Changes of blood pressure (BP) levels
      related to the presence of insulin resistance (IR) may be present in the GH
      deficient adult prior to or after therapy with recombinant GH (hGH). The purpose
      of the study was to assess the relationship between BP and IR in GH-deficient
      adults after 24 months of replacement with hGH. Thirteen GH-deficient adults were
      studied [7 men and 6 women, with an average age of 38.6+/-14.14 yr body mass
      index (BMI) 25.83+/-2.26 kg/m2]. The BP was assessed by means of ambulatory
      monitoring of BP (AMBP), prior to the treatment and 12 and 24 months after
      replacement with hGH. Glucose metabolism was assessed by the homeostatic model
      assessment (HOMA), during the same periods. The average dosage of hGH utilized
      was 0.67+/-0.15 mg/day. In the analysis of BP levels, we observed a decrease of
      the diurnal systolic BP (SB P) (p=0.043) and a reduction of the diurnal systolic
      (p=0.002) and diastolic pressure loads (p=0.038). During the night there were no
      changes in BP levels. We observed an increase in the percentage of patients with
      a non-physiological nocturnal fall (non dippers) after replacement with hGH
      (61.53%). The mean HOMA, insulin and glucose in the fasting state did not present
      any statistically significant changes. Although the patients within the nondipper
      group had higher HOMA and insulin levels throughout the study, there were no
      changes in any of these parameters after GH replacement. All patients with HOMA
      >2.5 were within the non-dipper group, whereas all dippers had HOMA <2.5. In
      conclusion, 24 months of therapy with hGH do not seem to have affected glucose
      homeostasis, and since there is no relationship with the increase of the
      percentage of non-physiological nocturnal fall, we will need a longer observation
      time to discover the effects of this finding.

PMID- 17556868
TI  - Comparison of predictive equations for resting energy expenditure in severely
      obese Caucasian children and adolescents.
AB  - The objective of the present study was to compare resting energy expenditure
      (REE) calculated by different predictive equations (McDuffie, Derumeaux,
      Tverskaya, Schofield, FAO/WHO/ UNU, Harris-Benedict and Lazzer-Sartorio) to REE
      measured in severely obese Caucasian children and adolescents. Two hundred and
      eighty-seven obese children and adolescents (121 males, 166 females, mean age:
      14.5 yr, mean body mass index (BMI) z-score: 3.3) participated in this study. REE
      was measured (MREE) by indirect calorimetry and body composition by bioelectrical
      impedance analysis. The FAO/WHO/UNU equations showed the lowest mean difference
      between predicted resting energy expenditure (PREE) and MREE (+0.2%, p=ns), but
      the higher SD (+/-1.16 MJ) and the PREE were accurate in 26% of subjects. The
      Tverskaya, Derumeaux and Harris-Benedict equations significantly underestimated
      REE in all children and adolescents (-7.6, -4.1, and -2.4%, respectively,
      p<0.05), while the Schofield and McDuffie equations overestimated REE (+2.5, +5
      and 25%, respectively, p<0.05). By contrast, the Lazzer-Sartorio equations showed
      the greater agreement and accuracy (in 55% of subjects) between mean PREEs and
      MREE for all children and adolescents, as well as for boys and girls (+1.6%,
      p=ns). In conclusion, Lazzer-Sartorio equations showed an accurate estimation of
      REE in groups of severely obese children and adolescents, resulting in lower mean
      differences and SD and higher accuracy between PREE and MREE than the other
      equations considered in this study.

PMID- 17556869
TI  - Ultrasonography thyroid volume estimation in hyperthyroid patients treated with
      individual radioiodine dose.
AB  - Radioiodine (RAI) therapy is a safe and effective treatment for hyperthyroidism
      and individual doses are frequently administered. Initial thyroid volume (TV) is
      an important parameter for RAI therapy. Ultrasonography (US) is considered the
      most reliable method of determining TV. The aim of this study was to evaluate TV
      by means of US in a cohort of 75 hyperthyroid patients before and after RAI
      therapy. According to clinical examination, thyroid US and technetium-99m (99mTc)
      pernechnetate scintiscan, the diagnosis of hyperthyroidism was multinodular
      goiter (MNG) in 27, diffuse goiter (DG) in 32 and uninodular goiter (UNG) in 16
      patients. The RAI dose to be administered was calculated according to TV and RAI
      uptake, up to a maximum of 600 MBq. TV was further evaluated 1, 3 and 6-12 months
      after RAI therapy. The initial TV was 42.3+/-4.0 ml for MNG, 29.7+/-2.8 ml for DG
      and 34.5+/-3.7 ml for UNG. After 6-12 months a non-significant TV reduction was
      observed in the MNG group even though the fraction of initial TV was 53.3+/-6.5%.
      Moreover, a significant TV reduction was noticed in the DG group (8.8+/-2.3 ml;
      p<0.001). In this group the fraction of initial TV was 28.6+/-3.2% at 6-12 month
      evaluation. A less marked, though still significant (p=0.04) TV reduction (19.6+/
      3.2 ml) was also observed in the UNG group, the fraction of initial TV being
      57.8+/-5.3% 6-12 months after RAI. In the whole patient population there was no
      significant correlation between TV reduction or TV at the last examination and
      initial TV, RAI dosage, baseline free T4 and TSH levels. No correlation was found
      between clinical condition at the last examination and TV reduction. In
      conclusion, these data justify TV estimation by means of US in the protocol of
      individual RAI dose for the therapy of hyperthyroidism. Our follow-up documents a
      poorly predictable TV reduction in all clinical conditions, but this is more
      pronounced and predictable in patients with diffuse toxic goiter.

PMID- 17556870
TI  - Increased plasma levels of visfatin/pre-B cell colony-enhancing factor in obese
      and overweight patients with metabolic syndrome.
AB  - BACKGROUND: Visfatin [pre-B cell colony- enhancing factor (PBEF)] is a cytokine
      highly expressed in visceral fat that exhibits insulin-mimetic properties.
      However, its role in insulin-resistant states, such as in metabolic syndrome
      (MetS), remains largely unknown. OBJECTIVE: To investigate the possible
      differences of plasma visfatin levels between obese and overweight subjects with
      and without MetS. DESIGN AND PATIENTS: Plasma visfatin concentrations were
      measured with enzyme-linked immunosorbent assay (ELISA) in 28 overweight and
      obese [body mass index (BMI)>28 kg/m2] subjects with Mets and 28 age- and sex
      matched overweight and obese (BMI>28 kg/m2) individuals without MetS (control
      group). RESULTS: Patients with MetS exhibited significantly elevated waist
      circumference (WCR ) values, higher blood pressure readings, higher fasting
      glucose and triglyceride concentrations as well as lower levels of HDL
      cholesterol (HDL-C) compared with controls. Total and LDL cholesterol (LDL-C)
      concentrations did not differ significantly between the two groups. Plasma
      visfatin concentrations were significantly higher in subjects with MetS compared
      with controls [27 (16- 65) ng/ml vs 19 (10-47) ng/ml, p<0.05]. The same results
      were observed even after adjustment for age, sex and BMI. Plasma visfatin levels
      were positively correlated with age (r=0.32, p<0.05), WCR (r=0.31, p<0.05),
      triglyceride (r=0.59, p<0.01) and glucose (r=0.33, p<0.05) levels and were
      negatively correlated with HDL-C levels (r=-0.38, p<0.05). Multiple linear
      regression analysis revealed similar results. CONCLUSION: Plasma visfatin levels
      are increased in overweight and obese subjects with MetS compared with those
      individuals who do not fulfil the criteria for the diagnosis of MetS.

PMID- 17556871
TI  - Primary hepatic carcinoid tumor presenting as Cushing's syndrome.
AB  - Hepatic carcinoid tumors are very uncommon; most are clinically non-functional
      and very few present with the symptoms of carcinoid syndrome. ACTH-producing
      carcinoid tumors most commonly originate in the lung or thymus and present
      insidiously with bronchospasm and/or chest mass. Occasionally, ectopic ACTH
      syndromes have been reported in association with pancreatic islet cell tumors,
      medullary thyroid cancer, pheochromocytoma, small-cell lung carcinoma, and
      rarely, ovarian and prostate tumors. We report here a patient with an ectopic
      ACTH-secreting primary hepatic carcinoid tumor who presented with cushingoid
      appearance, profound proximal muscle weakness, severe lower extremity edema, and
      markedly elevated urinary free cortisol. ACTH levels were in the low normal
      range. A solitary vascular hepatic lesion was found on magnetic resonance
      imaging, which was isodense with the surrounding liver on octreotide scan and
      photopenic on an 18-fluorodeoxyglucose (18FDG)-positron emission tomography (PET)
      scan. Following surgical resection of the hepatic tumor, histopathology confirmed
      an ACTH-secreting neuroendocrine tumor (NET), the patient had complete resolution
      of hypercortisolemic symptoms and remains in remission, now 4 yr after hepatic
      tumor resection. This case reports the first ACTH-secreting primary hepatic NET
      presenting as ectopic Cushing's syndrome. Interesting aspects of this case
      include the presence of a pituitary incidentaloma, the low normal ACTH, and
      photopenia on 18FDG-PET imaging.

PMID- 17556872
TI  - In vivo response to growth hormone-releasing peptide-6 in adrenocorticotropin
      dependent Cushing's syndrome by lung carcinoid tumor is associated with growth
      hormone secretagogue receptor type 1a mRNA expression.
AB  - GH secretagogues (GHS) have been used for the differential diagnosis of ACTH
      dependent Cushing's syndrome (CS) since 1997 due to their ability to increase
      ACTH and cortisol levels in Cushing's disease. The aim of this study was to
      correlate ACTH response to GH-releasing peptide-6 (GHRP-6) in vivo with GH
      secretagogue receptor type 1a (GHSR-1a) mRNA expression in a patient with lung
      carcinoid tumor. The patient was a 26-yr-old male with diagnosis of ACTH
      dependent CS. He presented negative responses to human CRH and desmopressin
      tests; yet, a significant increase in ACTH after the GHRP-6 test was observed.
      Sellar magnetic resonance imaging (MRI) showed slight posterior hypointensity,
      but bilateral petrosal sinus sampling did not show central gradient. Computed
      tomography (CT) and MRI of thorax/abdomen/cervical were negative and 111In
      pentetreotide scintigraphy depicted abnormal uptake on the right lung. The
      patient was submitted to right thoracotomy for exeresis of lung nodule and hilar
      lymph node which were characterized as atypical lung carcinoid tumor and he
      presented clinical and laboratorial remission after surgery. GHSR-1a mRNA
      expression was studied with real-time quantitative PCR and tumor data were
      compared with fragments of normal lung and pituitary. There was a higher GHSR-1a
      expression in the lung carcinoid tumor as compared with normal tissues. The ACTH
      response to GHRP-6 in a patient with ectopic ACTH production by a lung carcinoid
      tumor was associated with GHSR-1a expression in the tumor tissue, suggesting an
      association between GHSR-1a mRNA overexpression and the in vivo response to GHS.

PMID- 17556873
TI  - Hypokalemic periodic paralysis in a patient with acquired growth hormone
      deficiency.
AB  - CONTEXT: Hypokalemic periodic paralysis (HypoPP) is a rare disorder consisting of
      sudden episodes of muscle weakness with areflexia involving all four limbs, which
      spontaneously resolve within several hours or days. Primary HypoPP is genetically
      determined, while secondary acquired HypoPP has been described in association
      with thyreotoxycosis, hyperaldosteronism, kidney diseases, diuretics and
      liquorice abuse, gastrointestinal potassium loss, or cysplatinum therapy.
      OBJECTIVE: To report a case of HypoPP associated with GH deficiency. PATIENT: A
      33 yr-old man with hypopituitarism and diabetes insipidus secondary to pituitary
      stalk-localized sarcoidosis, and documented HypoPP episodes. CLINICAL
      PRESENTATION: Neurologic exam outside HypoPP episodes was normal. Needle
      electromyography was normal without myotonia or other spontaneous electric
      activity. Muscle biopsy documented a vacuolar myopathy with tubular aggregates.
      However, genetic analysis ruled out common mutations of the voltage-gated calcium
      channel observed in primary HypoPP. Common causes of secondary HypoPP were also
      ruled out. The patient was diagnosed with severe GH deficiency with modest
      fasting hyperinsulinemia and insulin resistance and started on GH replacement
      therapy, an alpha-glucosidase inhibitor (acarbose) and a diet low in simple
      carbohydrates. CONCLUSIONS: GH replacement therapy, acarbose and a diet low in
      simple carbohydrates resulted in the complete long-term (>2 yr) remission of
      HypoPP episodes. This is consistent with the hypothesis that the hyperinsulinemia
      associated to GH deficiency may trigger HypoPP episodes by increasing Na+/K+
      ATPase activity and K+ transport into the intracellular compartment with
      subsequent hypokalemia.

PMID- 17556874
TI  - Acute suppurative thyroiditis in childhood: relative frequency among thyroid
      inflammatory diseases*.

PMID- 17556876
TI  - Angiotensin converting enzyme inhibition in cardiovascular risk populations: a
      practical approach to identify the patient who will benefit most.
AB  - PURPOSE OF REVIEW: Evidence from clinical trials suggests that angiotensin
      converting enzyme (ACE) inhibition has the broadest impact of any class of drugs
      in cardiovascular medicine, reducing cardiovascular morbidity and mortality. This
      beneficial effect varies across different patient populations, however. This
      review will summarize the current literature about the therapeutic potential of
      ACE inhibition and provide a practical approach for clinicians to identify
      patients who benefit most from ACE inhibition. RECENT FINDINGS: ACE inhibition
      has been shown to benefit patients with heart failure, left ventricular
      dysfunction, postmyocardial infarction, nephropathy, peripheral vascular disease,
      diabetes, stroke or transient ischemic attack. The absolute clinical benefit
      varies across different risk populations, however, depending on the patient
      characteristics. ACE inhibitors are most effective in patients with an increased
      cardiovascular risk associated with an activated renin-angiotensin system and
      less effective in patients with classical cardiovascular risk factors, but
      without an activated renin-angiotensin system. SUMMARY: We argue that markers of
      an activated renin-angiotensin system, such as left ventricular dysfunction, left
      ventricular hypertrophy, renal dysfunction, as assessed by estimated glomerular
      filtration rate, or urinary albumin excretion, may be used as targets and act as
      indicators for ACE-inhibition therapy and also for monitoring purposes. This will
      help clinicians to guide their therapy and identify patients who benefit most
      from ACE inhibition.

PMID- 17556877
TI  - The role of clopidogrel in the management of ischemic heart disease.
AB  - PURPOSE OF REVIEW: Platelet inhibition remains a key component in the prevention
      and treatment of ischemic heart disease. This review documents recent advances in
      the use of clopidogrel for the management of myocardial ischemia. RECENT
      FINDINGS: For the prevention of ischemic heart disease, the addition of
      clopidogrel is not superior to aspirin alone at reducing short or long-term major
      adverse cardiac events. In patients with ST-segment elevation myocardial
      infarction who receive thrombolytics, clopidogrel therapy confers broad benefits
      including survival when initiated at the time of presentation. Long-term
      administration of clopidogrel is necessary to prevent thrombotic complications
      following coronary stent placement. Overall, there are no major safety concerns
      across the spectrum of cardiac indications for clopidogrel. SUMMARY: Clopidogrel
      has become a cornerstone of therapy in the treatment of acute ischemic coronary
      syndromes and as prevention of thrombosis after coronary stenting. It has
      demonstrated safety and efficacy in most aspects of ischemic heart disease.
      Questions remain about optimal duration of therapy following deployment of drug
      eluting stents.

PMID- 17556878
TI  - Smoking cessation: lessons learned from clinical trial evidence.
AB  - PURPOSE OF REVIEW: Cigarette smoking and exposure to secondhand smoke cause
      coronary heart disease. Cessation dramatically reduces the incidence of primary
      and secondary cardiac events. The review presents up-to-date information
      regarding nicotine dependence, recent findings related to its treatment, and
      recommendations for addressing smoking cessation for the primary and secondary
      prevention of coronary heart disease. RECENT FINDINGS: Bans on smoking in public
      places are associated with significant reductions in the incidence of acute
      myocardial infarction. Counseling and pharmacotherapy (nicotine replacement
      therapy, bupropion) are proven, effective treatments for nicotine dependence.
      Clinical trials of two new pharmacotherapies, varenicline and rimonabant, have
      recently been reported. Varenicline is a safe and efficacious medication for
      smoking cessation, and has been approved in the US, Canada and Europe. Rimonabant
      has shown mixed results for smoking cessation and is undergoing further
      evaluation. SUMMARY: All patients should be screened for tobacco use. Clinicians
      can effectively treat nicotine dependence in the general population using
      counseling and first-line pharmacotherapies (nicotine replacement therapy,
      bupropion, varenicline). These same treatments, with some modification, are
      appropriate for smokers with coronary heart disease; however, brief interventions
      without follow-up are not effective in this population. For smokers with coronary
      heart disease, the best time to intervene may be during hospitalization.

PMID- 17556879
TI  - Depression and ischemic heart disease: what have we learned from clinical trials?
AB  - PURPOSE OF REVIEW: Discuss the interplay of depression and ischemic heart
      disease. Studies demonstrate high prevalence of depression and its negative
      impact among patients with ischemic heart disease. RECENT FINDINGS: Results
      extend previous findings among men, demonstrating a significant increase in
      mortality and cardiovascular events among depressed women. Sertraline, citalopram
      and mitrazapine have been shown to be safe and well tolerated in patients with
      ischemic heart disease. Sertraline and citalopram have demonstrated efficacy for
      treating depression in such patients. Mirtazapine did not have significant
      efficacy on post-myocardial infarction depression. Cognitive-behavioral therapy
      and interpersonal therapy have not been found to have a significant treatment
      effect. Treating depression may have an impact on cardiovascular morbidity and
      mortality, but this has not yet been adequately studied. Studies to date lack
      sufficient statistical power to fully examine the impact of interventions for
      depression on cardiovascular outcomes. SUMMARY: Cardiologists encounter
      depression among 25-30% of their patients with ischemic heart disease. Depression
      is an independent risk factor for poor prognosis among ischemic heart disease
      patients, at a level comparable to several conventional cardiac risk factors.
      Adequate treatment of depression may improve the poor prognosis of depressed
      patients with ischemic heart disease.

PMID- 17556880
TI  - Current status of genome-wide scanning for hypertension.
AB  - PURPOSE OF REVIEW: The current review focuses on new trends in genome-wide
      assessment of the inherited component of blood pressure variation. RECENT
      FINDINGS: Systematic linkage and association analyses of a region on chromosome
      1q, complemented by gene prioritization with comparative genomic evidence,
      revealed variants in three genes contributing to tangible increases in blood
      pressure. The results of one of the first two-dimensional scans were published,
      confirming the oligogenic epistatic nature of the genetic component of blood
      pressure determination. Several loci with distinct effects on blood pressure in
      men and women were reported, enhancing the sexually dimorphic map of complex
      traits. Novel approaches were applied to extract genetically and clinically
      distinct subsets of garden-variety hypertension, which appears to be a promising
      direction to take in deciphering the hypertension genetic puzzle. SUMMARY: The
      current landscape of genome-wide linkage studies of hypertension is acquiring
      novel facets in an attempt to more appropriately grasp the genomic architecture
      of hypertension. The advent of genome-wide association investigations, enhanced
      possibilities of comparative genomics and integration with information on copy
      number variations and transcriptomics will most likely reshape our view of nature
      and the evolutionary connotations of genetic variation affecting blood pressure
      in the near future.

PMID- 17556881
TI  - Salt, blood pressure and cardiovascular disease.
AB  - PURPOSE OF REVIEW: To review the evidence that relates salt intake to blood
      pressure and cardiovascular disease. RECENT FINDINGS: Raised blood pressure
      throughout the range seen in developed countries is the major cause of
      cardiovascular disease, responsible for 62% of strokes and 49% of coronary heart
      disease. There is overwhelming evidence that dietary salt is a major cause of
      raised blood pressure, and a modest reduction in salt intake lowers blood
      pressure, which is predicted to reduce cardiovascular disease. Several lines of
      evidence including ecological, population and prospective cohort studies, as well
      as follow-up studies of individuals who participated in short-term salt reduction
      trials, have consistently shown a direct relation between salt intake and
      cardiovascular risk, and a reduction in population salt intake is associated with
      a reduction in cardiovascular mortality in the population. SUMMARY: The evidence
      for universal salt reduction is strong, and reducing salt from the current intake
      of 10-12 g/day to the recommended level of 5-6 g/day will have a major effect on
      blood pressure and cardiovascular mortality. Additionally, this will result in
      considerable savings on health expenditure as, not only is raised blood pressure
      the biggest cause of death, but the second biggest cause of disability worldwide.

PMID- 17556882
TI  - Sodium, blood pressure, and cardiovascular disease.
AB  - PURPOSE OF REVIEW: Persistent recommendations for universal restriction of
      dietary sodium intake are based on associations of sodium intake with blood
      pressure. No clinical trial data support an association of sodium intake with
      mortality and morbidity outcomes, however, while results of observational studies
      appear heterogeneous. Can these contradictory data be reconciled to inform health
      policy regarding sodium intake recommendations? RECENT FINDINGS: We reported
      (2006) a statistically significant (P = 0.03) association of sodium intake less
      than 2.3 g/day with increased cardiovascular disease mortality (hazard ratio
      1.37) in a representative sample of the US adult population with an observed
      baseline mean sodium intake of 2.7 g/day. Others reported (2004) a significant (P
      < 0.01) higher stroke death among males and borderline significant (P = 0.07) for
      females, for highest compared with lowest sodium tertile in a community in Japan
      with mean intake of 5.4 g/day. SUMMARY: These results are consistent with earlier
      studies suggesting that the association of sodium with morbidity and mortality in
      industrial societies follows a 'J shape' with a direct association at high levels
      of average intake (over 4 g), an inverse association at lower levels (less than 2
      g) and no measurable effect for the widely prevalent intakes in between.

PMID- 17556883
TI  - Angiotensin II and oxidative stress.
AB  - PURPOSE OF REVIEW: Angiotensin II regulates vasoconstriction, homeostasis of salt
      and water, and cardiovascular hypertrophy and remodeling. Angiotensin II is a
      potent activator of NAD(P)H oxidase in the cardiovascular system, and augments
      production of reactive oxygen species. Numerous signaling pathways in response to
      angiotensin II are mediated by reactive oxygen species and oxidative stress is
      deeply associated with the progression of cardiovascular disease. The purpose of
      this review is to discuss the mechanism of reactive oxygen species formation and
      the pathophysiological effects of angiotensin II in the cardiovascular system.
      RECENT FINDINGS: Recent studies have demonstrated novel molecular mechanisms of
      reactive oxygen species generation by angiotensin II and signaling pathways
      including cell proliferation, hypertrophy and apoptosis. In spite of these
      findings that strongly suggest the benefits of angiotensin II inhibition for
      cardiovascular disease, the clinical effects of angiotensin II-induced reactive
      oxygen species on the cardiovascular system are still controversial. SUMMARY: We
      focus on the effects of angiotensin II-induced oxidative stress on cardiovascular
      function and remodeling after discussing the source of reactive oxygen species
      and novel signaling pathways in response to reactive oxygen species.

PMID- 17556884
TI  - Endothelial function and hypertension.
AB  - PURPOSE OF REVIEW: Endothelial dysfunction, in particular a reduced vascular
      availability of endothelium-derived nitric oxide, has been analysed in numerous
      experimental and clinical studies as a potential mechanism mediating the adverse
      vascular effects of hypertension. This paper outlines some notable studies in
      this dynamic field published recently. RECENT FINDINGS: The understanding of
      mechanisms underlying endothelial dysfunction in hypertension has been
      substantially advanced recently. Increased oxidant stress is thought to represent
      a major mechanism leading to reduced vascular availability of endothelium-derived
      nitric oxide. Vascular nicotinamide adenine dinucleotide phosphate oxidases,
      uncoupled nitric oxide synthase and xanthine oxidase have been identified as
      major sources of reactive oxygen species in hypertension. Endothelial dysfunction
      has been implicated in the macrovascular complications of hypertension, such as
      stroke or myocardial infarction, coronary microvascular dysfunction and increased
      arterial stiffness, probably at least partly resulting from loss of the
      antiatherogenic and vasculoprotective effects of endothelium-derived nitric
      oxide. SUMMARY: Recent research on endothelial dysfunction supports its clinical
      significance in hypertension, and has led to important insights into the
      pathophysiology of the disease. These observations suggest that targeting
      endothelial dysfunction, in particular reduced nitric oxide availability, would
      exert beneficial effects in hypertensive patients. This concept needs further
      evaluation in clinical studies.

PMID- 17556885
TI  - Do we need out-of-office blood pressure in every patient?
AB  - PURPOSE OF REVIEW: The limitations affecting office blood pressure readings have
      spurred the development of techniques for measuring blood pressure out of a
      clinical environment. The increasing use of home and ambulatory blood pressure
      monitoring has allowed the identification of specific blood pressure patterns
      related either to a discrepancy between office and out-of-office blood pressure
      or to alterations in the 24-h blood pressure profiles. This review offers an
      update on the most recent data published on the above issues. RECENT FINDINGS: A
      critical overview is provided on recent data published on blood pressure patterns
      suggested to have clinical relevance. These include white coat hypertension, the
      so-called masked hypertension, enhanced overall blood pressure variability over
      24 h, a steeper morning blood pressure surge and a blunted or an excessive blood
      pressure fall at night. SUMMARY: All of these different conditions have been
      variably reported to carry prognostic implications, and may represent specific
      targets for antihypertensive treatment. Their identification and management
      require information on out-of-office blood pressure, which suggests that self
      blood pressure monitoring at home or 24-h ambulatory blood pressure monitoring
      should be used more frequently in clinical practice, following the indications
      issued in recent guidelines.

PMID- 17556886
TI  - Echocardiographic left ventricular hypertrophy in hypertension: marker for future
      events or mediator of events?
AB  - PURPOSE OF REVIEW: To discuss the most relevant studies on the prognostic impact
      of echocardiographic left ventricular hypertrophy in hypertension. RECENT
      FINDINGS: There is abundant evidence from epidemiological studies that increased
      left ventricular mass identifies hypertensive patients at increased risk of major
      cardiac and cerebrovascular events. Looking at the geometric patterns of the left
      ventricle, concentric remodelling and concentric left ventricular hypertrophy
      carry the highest risk for adverse events. Patients with left ventricular
      hypertrophy reversal as an effect of treatment are exposed to a lesser risk of
      events as compared with patients with persistence of left ventricular
      hypertrophy. Reversal of concentric remodelling predicts a lesser risk of adverse
      events compared with persistence of remodelling. Experimental evidence is
      accumulating that several haemodynamic and nonhaemodynamic factors which are able
      to promote progression of atherosclerosis through plaque growth and
      destabilization may also induce left ventricular hypertrophy by acting on myocyte
      and interstitium. Increased left ventricular mass may also be a causative factor
      for reduced pumping performance and arrhythmias. SUMMARY: Increased left
      ventricular mass is a marker of cardiovascular risk because it reflects and
      integrates the long-term level of activity of factors inducing progression of
      atherosclerosis. Increased left ventricular mass may also mediate myocardial
      ischaemia with potential evolution towards heart failure and arrhythmias.

PMID- 17556887
TI  - 'Beyond blood pressure' means multiple risk factor intervention, not pleiotropic
      antihypertensive drugs.
AB  - PURPOSE OF REVIEW: We examined the role of blood pressure-lowering compared with
      class-specific properties of antihypertensive drugs in cardiovascular prevention.
      RECENT FINDINGS: We reviewed recently published trials and meta-regression
      analyses. SUMMARY: From 150,000 to 180,000 randomized patients followed up from 3
      to 5 years were required to demonstrate a 10-15% benefit 'beyond blood pressure
      lowering' of newer antihypertensive drugs, such as calcium channel blockers or
      angiotensin-converting enzyme inhibitors in the prevention of cause-specific
      cardiovascular complications. Assuming an absolute risk of new-onset diabetes
      mellitus on older drugs of approximately 10% over 5 years and a relative benefit
      on the newer drugs of approximately 30%, about 100 patients would have to be
      treated for 5 years with the newer agents to avert approximately three iatrogenic
      cases of diabetes. Whether or not new-onset diabetes is associated with increased
      risk is uncertain. In most patients, optimization of treatment at acceptable
      tolerance requires rotation through and combination of several drug classes.
      Combination of different classes of antihypertensive drugs not only enhances the
      blood pressure-lowering efficacy, but likely decreases the risk of metabolic
      adverse effects as well. True benefit beyond blood pressure lowering in
      hypertensive patients comes from multiple risk factor intervention.

PMID- 17556888
TI  - Genetic determinants of HDL: monogenic disorders and contributions to variation.
AB  - PURPOSE OF REVIEW: This review focuses on recent progress towards the
      characterization of genetic variations that contribute to interindividual
      variation in plasma high-density lipoprotein cholesterol levels in the general
      population. RECENT FINDINGS: Many of the genes that harbor rare mutations leading
      to extreme high-density lipoprotein cholesterol levels contain common variation
      that influences plasma high-density lipoprotein cholesterol in several study
      populations. Candidate gene association studies provide evidence that some of
      these variations have an effect on high-density lipoprotein cholesterol,
      dependent on epistatic interactions or environmental context. Both rare and
      common variations contribute to interindividual high-density lipoprotein
      cholesterol variation. Recent comparisons of candidate gene sequences between
      individuals in the tails of the high-density lipoprotein cholesterol
      distributions (the upper or lower 1-5%) of several study populations indicate
      that as many as 20% of individuals with low high-density lipoprotein cholesterol
      harbor a rare mutation in an investigated gene. For example, the ABCA1 gene
      region harbors rare mutations and common variants that contribute to
      interindividual high-density lipoprotein cholesterol variation in the general
      population. SUMMARY: The genetic control of high-density lipoprotein cholesterol
      level is complex. Maximizing the utility of genetic knowledge for predicting an
      individual's high-density lipoprotein cholesterol level or response to
      intervention will require a better understanding of the action of combinations of
      genetic variants and environmental exposures.

PMID- 17556889
TI  - Inconsistencies in the genetic prediction of HDL cholesterol versus
      atherosclerosis.
AB  - PURPOSE OF REVIEW: High-density lipoprotein (HDL) is generally perceived as
      having a protective role with respect to cardiovascular disease. The metabolism
      of HDL is mediated through a complex network of apoproteins, enzymes and transfer
      proteins. Genetic variants within this network can increase plasma HDL, but not
      with uniformly beneficial clinical outcomes. The purpose of this review is to
      explore and propose mechanisms for these discrepant observations. RECENT
      FINDINGS: Recent developments in this area include new observations of genetic
      variants that paradoxically increase both HDL and cardiovascular risk. Also
      discussed are newly observed, function-altering modifications of the HDL
      particle. Proposed explanations include the segregation of the genetic variants
      associated with the respective endpoints of plasma HDL and cardiovascular risk.
      Functionally impaired but quantitatively robust plasma HDL and the emerging
      understanding of proinflammatory HDL also may contribute to our understanding of
      discordant observations. SUMMARY: Enhanced understanding of these relationships
      may allow a more accurate assessment of clinical risk based on plasma HDL and
      help explain why HDL may, in some circumstances, be an inappropriate therapeutic
      target.

PMID- 17556890
TI  - Apolipoprotein A-I versus HDL cholesterol in the prediction of risk for
      myocardial infarction and stroke.
AB  - PURPOSE OF REVIEW: To compare the potential of high-density lipoprotein (HDL)
      cholesterol and apolipoprotein (apo) A-I, the major protein in HDL particles, in
      predicting cardiovascular risk. Pros and cons for using these risk markers are
      discussed. RECENT FINDINGS: Both HDL cholesterol and apoA-I are in most clinical
      conditions antiatherogenic - the higher the values, the lower the cardiovascular
      risk. Methodological and physiological factors speak in favour of using apoA-I
      rather than HDL cholesterol as a marker of risk. In prospective risk studies and
      in lipid-lowering trials it has been shown that the apoB/A-I ratio, which
      reflects the cholesterol balance between all potentially atherogenic (apoB) and
      antiatherogenic lipoproteins (apoA-I), is a better risk marker than low-density
      lipoprotein cholesterol, HDL cholesterol and lipid ratios in predicting
      cardiovascular risk and response to lipid lowering induced by statins. Practical
      advantages speak in favour of using apoB and apoA-I - fasting is not needed to
      analyze and interpret the values of apoB and apoA-I. SUMMARY: New guidelines
      should be developed in which target values for apoB and apoA-I are defined to
      enable the use of these new strong risk markers/factors in clinical practice.

PMID- 17556891
TI  - Molecular regulation of macrophage reverse cholesterol transport.
AB  - PURPOSE OF REVIEW: Macrophage reverse cholesterol transport is one of the key
      mechanisms mediating the protective effects of high-density lipoproteins on
      atherosclerosis. This review focuses on the recent developments in our
      understanding of molecular mechanisms of macrophage reverse transport and
      regulators that play important roles during this process. RECENT FINDINGS:
      Macrophage reverse cholesterol transport is promoted by apolipoprotein A-I
      overexpression and reduced in the setting of apolipoprotein A-I deficiency. A
      liver X receptor agonist markedly increases macrophage reverse cholesterol
      transport. ATP-binding cassette transporter A1 and ATP-binding cassette
      transporter G1 are liver X receptor-responsive macrophage genes that promote
      cholesterol efflux to lipid-free apolipoprotein A-I and mature high-density
      lipoprotein, respectively. The direct roles of ATP-binding cassette transporter
      A1 and ATP-binding cassette transporter G1 in macrophage reverse cholesterol
      transport in vivo remain unclear. Therapeutically promoting macrophage reverse
      cholesterol transport has been recognized as one of the promising means to
      prevent atherosclerosis. SUMMARY: Increasing evidence has suggested that ATP
      binding cassette transporter A1 and ATP-binding cassette transporter G1 are
      involved in macrophage reverse cholesterol transport. In-depth understanding of
      the molecular mechanisms will enable us to develop new therapeutic means to
      protect against atherosclerosis.

PMID- 17556892
TI  - Where are we with high-density lipoprotein raising and inhibition of cholesteryl
      ester transfer for heart disease risk reduction?
AB  - PURPOSE OF REVIEW: To review recent research in the area of high-density
      lipoprotein raising and coronary heart disease risk reduction. RECENT FINDINGS: A
      decreased high-density lipoprotein-cholesterol is an important coronary heart
      disease risk factor and raising high-density lipoprotein-cholesterol has been
      associated with coronary heart disease risk reduction. A relative new strategy
      for raising high-density lipoprotein-cholesterol, i.e. inhibition of cholesteryl
      ester transfer protein, is markedly effective. Cholesteryl ester transfer protein
      inhibitors prevent the transfer of cholesteryl ester from high-density
      lipoprotein to triglyceride-rich lipoproteins in exchange for triglyceride. One
      inhibitor, torcetrapib, binds to cholesteryl ester transfer protein on high
      density lipoprotein, markedly raises high-density lipoprotein-cholesteryl ester
      and has no effect on fecal cholesterol excretion, but can raise blood pressure. A
      large clinical trial in coronary heart disease patients on atorvastatin was
      recently stopped prematurely because of excess mortality in those receiving
      torcetrapib vs. placebo and two other trials reported no benefit of torcetrapib
      on coronary atherosclerosis or carotid artery intimal medial thickness as
      compared with subjects on atorvastatin alone. SUMMARY: The adverse effects of
      torcetrapib may be compound-specific and, since the crystal structure of
      cholesteryl ester transfer protein is now known, it should be possible to develop
      more optimal cholesteryl ester transfer protein inhibitors that do not form a
      nonproductive complex with cholesteryl ester transfer protein on the high-density
      lipoprotein particle, as has been reported for torcetrapib. The alternative for
      high-density lipoprotein raising is to develop more effective and better
      tolerated niacin preparations.

PMID- 17556893
TI  - Bibliography. Current world literature. Clinical trial.

PMID- 17556895
TI  - Double balloon (push-and-pull) enteroscopy: breakthrough in the management of
      small intestinal strictures in Crohn's disease?
AB  - Development of strictures is common in Crohn's disease, leading to resective
      surgery in many cases. Endoscopic balloon dilation has been used alternatively,
      to treat short fibrotic strictures to avoid resection. Although the small bowel
      is a predominant site of strictures in Crohn's disease, endoscopic access had
      been limited. With the advent of double balloon (push-and-pull) enteroscopy,
      visualization of small intestinal stenoses has become possible. In the case of
      short fibrotic strictures hydrostatic balloon dilation can be performed. Pohl et
      al. report in this issue (Eur J Gastroenterol Hepatol 19:529-534) a first series
      of patients with suspected small bowel strictures that were confirmed by double
      balloon enteroscopy. Hydrostatic balloon dilation was feasible and safe in
      selected patients with short fibrotic stenosis, favorable anatomy and absence of
      severe inflammation. After dilation, nearly half of the patients had a clinical
      benefit without need for surgery after 10 months. On the basis of encouraging
      results of this first series, future studies will have to show general
      feasibility, safety and long term outcomes in larger cohorts.

PMID- 17556896
TI  - Upper gastrointestinal endoscopy or not, and in whom?
AB  - Despite progress in knowledge and effective therapies for acid-sensitive problems
      the indications for gastroscopy seem even more confusing than before. The primary
      care physician, faced with the patient with undifferentiated symptoms, is now
      less sure when to seek an endoscopy which is actively discouraged in many health
      care settings. Management guidelines, based essentially on maximizing the yield
      from endoscopy, may define the direction of travel but do not sit comfortably in
      the consultation setting.

PMID- 17556897
TI  - Diagnostic and therapeutic yield of push-and-pull enteroscopy for symptomatic
      small bowel Crohn's disease strictures.
AB  - OBJECTIVE: Crohn's disease is frequently complicated by obstructive symptoms
      secondary to small bowel strictures that cannot be accessed by conventional
      endoscopy. Push-and-pull enteroscopy is a new endoscopic tool that might allow
      not only diagnostic work-up but also therapeutic interventions of these
      strictures. The purpose of this study was to evaluate the feasibility and safety
      of push-and-pull enteroscopy in the treatment of symptomatic small bowel Crohn's
      disease strictures. METHODS: Between September 2003 and May 2006, 19 consecutive
      patients with known or suspected Crohn's disease and symptomatic small bowel
      strictures were subjected to push-and-pull enteroscopy and included in our
      analysis. RESULTS: With push-and-pull enteroscopy at least one small bowel
      stricture was accessed in each patient. On the basis of endoscopic assessment
      strictures in nine patients were not amenable to endoscopic therapy because of
      anatomical reasons (3/9) or severe inflammatory activity within the stenotic
      segment (6/9). They underwent direct surgery or intensified immunomodulatory
      treatment, respectively. In 10 patients with 13 strictures we performed 15
      dilations in combination with push-and-pull enteroscopy under fluoroscopic
      guidance. Technical success was achieved in 8/10 patients, symptomatic relief
      with avoidance of surgery was achieved in 6/10 patients who remained symptom free
      during a mean follow-up period of 10 months (range, 4-16 months). No
      complications were encountered after dilation. CONCLUSIONS: Push-and-pull
      enteroscopy is very useful for diagnosis and directing therapy in patients with
      Crohn's disease-associated strictures within the small bowel. Balloon dilation
      with the push-and-pull enteroscopy device appears safe and effective and can be
      considered as an alternative to surgery in selected patients with medically
      refractory strictures.

PMID- 17556898
TI  - Capsule enteroscopy vs. other diagnostic procedures in diagnosing obscure
      gastrointestinal bleeding: a cost-effectiveness study.
AB  - BACKGROUND: Capsule enteroscopy is considered the gold standard for evaluating
      patients with obscure gastrointestinal bleeding. The costs of capsule enteroscopy
      examination, however, make it uncertain whether the clinically relevant
      diagnostic gain is also associated with cost savings. AIM: To evaluate the
      incremental cost-effectiveness ratio of capsule enteroscopy in patients with
      obscure gastrointestinal bleeding. METHODS: Retrospective study was carried out
      in nine Italian gastroenterology units from 2003 to 2005. Data on 369 consecutive
      patients with obscure gastrointestinal bleeding were collected. The diagnostic
      yield of capsule enteroscopy vs. other imaging procedures was evaluated as a
      measure of efficacy. The values of Diagnosis Related Group 175 (euro 1884.00 for
      obscure-occult bleeding and euro 2141.00 for obscure-overt bleeding) were
      calculated as measures of economic outcomes in the cost analysis. RESULTS:
      Obscure and occult gastrointestinal bleeding was recorded in 177 patients (48%)
      with a mean duration of anemia history of 17.6+/-20.7 months. Among patients,
      60.9% had had at least one hospital admission, 21.2% at least two, and 1.2% of
      obscure bleeders up to nine admissions. Overall, 58.4% of patients had positive
      findings with capsule enteroscopy compared with 28.0% with other imaging
      procedures (P<0.001). The mean cost of a positive diagnosis with capsule
      enteroscopy was euro 2090.76 and that of other procedures was euro 3828.83 with a
      mean cost saving of euro 1738.07 (P<0.001) for one positive diagnosis.
      CONCLUSIONS: Capsule enteroscopy is a cost-saving approach in the evaluation of
      patients with obscure gastrointestinal bleeding.

PMID- 17556899
TI  - Management of patients with nonvariceal upper gastrointestinal hemorrhage before
      and after the adoption of the Rockall score, in the Italian Gastroenterology
      Units.
AB  - OBJECTIVES: Nonvariceal upper gastrointestinal hemorrhage is a frequent reason
      for ordinary hospital admission. In Italy the use of prognostic scores to
      stratify the risk has not been adequately validated: the impact on clinical
      management of a rating system like the Rockall score remains to be established.
      RING is a 'register' that has been collecting hospital discharge files from
      hospital gastroenterology units, giving a broad picture of the patients admitted
      for this pathology. METHODS: We analyzed the hospital discharge files collected
      between 2001 and 2005 from 12 gastroenterology units, which issued more than
      26,000 hospital discharge files for ordinary hospital admission and have been
      using the Rockall score for defining nonvariceal upper gastrointestinal
      hemorrhage since 2003. RESULTS: There were 2832 hospital discharge files with a
      main diagnosis of nonvariceal upper gastrointestinal hemorrhage: 1335 'before'
      the Rockall score was introduced, 1497 'after' the introduction. Patients' mean
      age was 67.7+/-16.7 years, with a male/female ratio of 1.7 and no significant
      changes over the years. There were no differences in the distribution of
      diagnoses in nonvariceal upper gastrointestinal hemorrhage patients before/after
      the introduction of the Rockall score, though the mean hospital stay became
      shorter (7.1+/-5.0 vs. 6.3+/-4.5 days), and mortality declined (2.8 vs. 2.3%), in
      parallel with the caselist as a whole. For 1102 ordinary hospital admission
      Rockall score was calculated. Diagnoses were more accurate: significantly fewer
      undefined causes and an increase in peptic ulcer. The mean Rockall score was
      4.6+/-2.2: 17.8% low (0-2), 48.7% intermediate (3-5), and 33.5% high (>or=6).
      Mean hospital stay, rebleeding, and mortality were correlated with the severity
      of the score. CONCLUSION: The Rockall score enables the clinician to formulate a
      more precise diagnosis and substantially shortens the time in hospital,
      especially for patients at low-risk of rebleeding and death, so more resources
      can be dedicated to critically ill patients.

PMID- 17556900
TI  - Implementation of a guideline versus use of individual prognostic factors to
      prioritize waiting lists for upper gastrointestinal endoscopy.
AB  - BACKGROUND: Studying factors associated with positive gastroscopies in dyspeptic
      patients can help limit and rationalize waiting lists for endoscopies. Dyspepsia
      guidelines have a controversial role because their main purpose is to provide
      specifications on efficient global management of primary care patients. AIM: To
      assess and weigh the risk of major endoscopic diagnoses against different age
      groups, gender, Helicobacter pylori infection, compliance with European Society
      of Primary Care Gastroenterology (ESPCG) guideline statements, and participation
      of prescribing general practitioners in a quality improvement programme for
      dyspepsia management, based on these guidelines. METHODS: We consecutively
      studied the outcomes of 752 gastroscopies with respect to two sets of useful
      results: the first considered diagnoses of carcinoma, gastric and duodenal ulcer;
      the second excluded duodenal ulcer. RESULTS: A diagnosis of cancer or
      gastric/duodenal ulcer was associated with male sex (odds ratio (OR)=1.81,
      P=0.016), age above 41 years (OR=3.24, P=0.009) and particularly with positivity
      to H. pylori (OR=4.49, P<0.001), while the risk increased by two and a half times
      in gastroscopies conforming with ESPCG guidelines (OR=2.47, P=0.003). In the
      second set of analysis, we noted a statistically significant correlation between
      cancer or gastric ulcer and compliance with ESPCG guidelines (OR=4.69, P=0.013),
      but not with H. pylori positivity (OR=1.83, P=0.11); a linear relationship was
      observed across age groups, with a 60% increase in the risk of disease with every
      5-year increase in age (OR=1.59, P=0.002). CONCLUSION: Participation of general
      practitioners in the Dyspepsia Management Programme (DMP) was not significantly
      associated with a positive gastroscopy.

PMID- 17556901
TI  - Effect of baseline symptom severity on patient-reported outcomes in
      gastroesophageal reflux disease.
AB  - OBJECTIVE: Patient-reported outcome instruments are becoming increasingly
      important tools in clinical trials. We aimed to investigate the effect of
      baseline symptom severity on: (i) a global rating of change using the Overall
      Treatment Effect questionnaire; (ii) the change from baseline for some commonly
      used questionnaires, namely the Gastrointestinal Symptom Rating Scale and the
      Quality of Life in Reflux and Dyspepsia questionnaire; and (iii) treatment
      differences assessed by Gastrointestinal Symptom Rating Scale in patients with
      symptoms of gastroesophageal reflux disease. METHODS: We used pooled data from
      two 4-week studies of patients with gastroesophageal reflux disease (but without
      endoscopically verified esophagitis) randomized either to esomeprazole (20 or 40
      mg) or to omeprazole 20 mg. We also used data from a study of omeprazole (10 or
      20 mg) or ranitidine 300 mg in gastroesophageal reflux disease patients with or
      without esophagitis. The analysis is based on descriptive statistics. RESULTS:
      Little impact of baseline symptoms/problems exists on the global rating of change
      (Overall Treatment Effect questionnaire). For example, the percentage of patients
      experiencing a large improvement with acid-suppressive therapy according to
      Overall Treatment Effect ranged from 63.2% for those with mild reflux at baseline
      to 70.3% for those with severe reflux. Change from baseline in the
      Gastrointestinal Symptom Rating Scale reflux dimension and quality of life in
      reflux and dyspepsia sleep disturbance and food/drink problems dimensions were
      associated with baseline symptoms/problems, with the largest change seen for
      patients with severe symptoms/problems at baseline. Baseline symptom severity was
      also associated with a clear effect on treatment differences, which tended to be
      larger for patients with severe symptoms than for patients with mild baseline
      symptoms. CONCLUSIONS: In patients with gastroesophageal reflux disease, baseline
      symptom/problem severity had little association with the global rating of change,
      whereas a clear association with change in symptoms/problems and on treatment
      differences was apparent. The magnitude of change increased with increasing
      baseline severity of symptoms/problems.

PMID- 17556902
TI  - Rugal hyperplastic gastritis increases the risk of gastric carcinoma, especially
      diffuse and p53-independent subtypes.
AB  - OBJECTIVES: Infection with Helicobacter pylori has been linked to chronic
      gastritis with atrophy or hyperrugosity. The development of noncardia gastric
      carcinoma, especially the intestinal type in Lauren's classification, has been
      associated with severe atrophic gastritis and p53 mutations. The objective of
      this study was to determine the association between hyperrugosity and gastric
      carcinogenesis, including p53 mutations. PARTICIPANTS AND METHODS: Barium meal
      roentgenograms were performed in 395 control participants and 132 gastric
      carcinoma patients. The fold width was measured at the greater curvature of the
      middle portion of the gastric body. Serum pepsinogens I and II were determined
      along with gastrin levels. Complete coding sequences and splice junctions for
      exons 5-8 of p53 gene were screened for mutations by polymerase chain reaction
      based single-strand conformational polymorphism analysis. RESULTS: Rugal
      hyperplastic gastritis (gastric body fold width>or=5 mm) increased the risk of
      gastric carcinoma [odds ratio, 2.60; 95% confidence interval, 1.69-4.01] as
      compared with the control group, especially diffuse-type gastric carcinoma (odds
      ratio, 4.13; 95% confidence interval, 2.36-7.24). The p53 mutational rate was
      significantly lower in gastric carcinoma patients with rugal hyperplastic
      gastritis. In intestinal-type gastric carcinoma with hyperrugosity, the incidence
      of p53 gene mutations decreased, but no association was found in diffuse-type
      gastric carcinoma between p53 mutations and rugal hyperplastic gastritis.
      CONCLUSIONS: Rugal hyperplastic gastritis was associated with an elevated risk of
      gastric carcinoma, especially diffuse-type, and a lower frequency of p53
      mutations.

PMID- 17556903
TI  - Metabolic and inflammatory faecal markers in collagenous colitis.
AB  - OBJECTIVES: To evaluate the excretion of the inflammatory and metabolic faecal
      markers calprotectin, lactoferrin, and short-chain fatty acids in symptomatic and
      quiescent collagenous colitis. METHODS: Faecal samples from 21 patients with
      active collagenous colitis, 12 patients retested in remission, and 13 controls
      were analysed. Calprotectin was determined using an enzyme-linked immunosorbent
      assay. Lactoferrin was estimated by a latex agglutination test. Short-chain fatty
      acids were determined by steam distillation followed by gas-liquid
      chromatography. RESULTS: Calprotectin was increased in patients with active
      collagenous colitis [80 microg/g (6.25-1899)] (median and range) compared with
      patients with quiescent collagenous colitis [26 microg/g (6.25-340)], P=0.025 and
      controls [6.25 microg/g (6.25-99)], P=0.002. Eight patients (38%) with active
      collagenous colitis had normal levels of calprotectin. Lactoferrin was detected
      in one patient only. Concentrations of total short-chain fatty acids did not
      differ in patients with active collagenous colitis compared with quiescent
      collagenous colitis or controls (P=0.75), whereas concentrations of the branched
      chain fatty acids were decreased in patients with active collagenous colitis
      versus controls (P<0.005). In-vitro incubations demonstrated increased ratios of
      acetate in patients with active and quiescent collagenous colitis compared with
      controls (P<0.05), with a corresponding decrease in branched-chain fatty acids
      ratios (P<0.05). CONCLUSION: Faecal calprotectin was increased in collagenous
      colitis; however, increased excretion was not a universal finding limiting the
      use of calprotectin as an inflammatory marker in collagenous colitis. Faecal
      lactoferrin was almost undetectable. Luminal fermentative conditions are altered
      in collagenous colitis. Fermentative alterations could be secondary to changes in
      substrate availability and intestinal transit time.

PMID- 17556904
TI  - Temperature-controlled radiofrequency energy (SECCA) to the anal canal for the
      treatment of faecal incontinence offers moderate improvement.
AB  - BACKGROUND AND AIM: Faecal incontinence is a devastating complaint. Even after
      conservative treatment, many patients still remain incontinent. Few patients have
      a sphincter defect suitable for repair. Other emerging surgical therapies like
      dynamic gracilis plasty, neuromodulation or artificial bowel sphincter, carry
      side effects and show only moderate improvement. Temperature-controlled
      radiofrequency energy (SECCA) has shown promising results in the USA. Local
      tightening seems to be the mode of action with possible increased rectal
      sensitivity. We investigated the effectiveness of radiofrequency and possible
      changes in the anal sphincter with 3D-ultrasound in patients with faecal
      incontinence. PATIENTS AND METHODS: Eleven women, mean age 61 years (49-73) with
      long-standing faecal incontinence were included. Patients with large sphincter
      defects and anal stenosis were excluded. The SECCA procedure was performed under
      conscious sedation and local anaesthesia. Oral antibiotics were given. In four
      quadrants on four or five levels (depending upon length of the anus)
      radiofrequency was delivered with multiple needle electrodes. Patients were
      evaluated at 0, 6 weeks, 3 and 6 months and 1 year. Three-dimensional anal
      ultrasound was performed at 0 (before and after the procedure), 6 weeks and 3
      months. Anal manometry and rectal compliance measurement were performed at 0 and
      3 months. RESULTS: At 3 months, six of 11 patients improved, which persisted
      during follow-up of 1 year. The Vaizey score changed from 18.8 to 15.0 (P=0.03)
      and in those improved from 18.3 to 11.5 (P=0.03). Anal manometry and rectal
      compliance showed no significant changes, there was a tendency to increased
      rectal sensitivity concerning urge and maximal tolerated volume (both P=0.3).
      Responders compared with nonresponders showed no difference in test results. Side
      effects were local haematoma (2), bleeding 3 days (1), pain persisting 1-3 weeks
      (4) and laxatives-related diarrhoea during 1-3 weeks (4). CONCLUSION: The SECCA
      procedure seems to be promising for patients with faecal incontinence with a
      persisting effect after 1 year. No significant changes in tests were found.

PMID- 17556905
TI  - Prokinetic effect of alpha-adrenergic antagonist, and beta-adrenergic antagonist
      on gall-bladder motility in humans with gall-stone disease.
AB  - INTRODUCTION: The effects of cholinergic agents and vagal control on gall-bladder
      motility are well defined. Alpha adrenergic antagonists have been found in
      previous studies to have a prokinetic effect on gall-bladder motility in normal
      human patients. Their effects have not, however, been fully elucidated in
      patients with gall-stone disease. OBJECTIVE: Our aim was to determine the effects
      of alpha-antagonists and beta-antagonists on gall-bladder motility in human
      patients with gall-stone disease. METHODS: In this single-blind, three-way
      crossover study, a slow release formulation of 80 mg propranolol (beta
      antagonist), and 25 mg indoramin (alpha-antagonist), and placebo were
      administered separately to 10 patients with gall-stone disease on three separate
      days 8 h before assessment of gall-bladder volumes by ultrasonography. Gall
      bladder volumes were assessed in the fasting state and at 5 min intervals for 50
      min after a standard proprietary enteral feed (Ensure 180 ml, Abbott).
      Differences between the placebo and postadrenergic antagonist scan volumes were
      tested using the Wilcoxon-signed rank test. RESULTS: There were no significant
      differences in the mean fasting gall-bladder volumes after receiving propranolol,
      indoramin and placebo (23.6+/-3.9, 22.3+/-4.3, 26.8+/-7.2 ml, mean+/-SEM,
      respectively). In the postprandial period, however, indoramin significantly
      enhanced postprandial gall-bladder emptying compared with placebo between 5 and
      30 min (P<0.05) after which refilling commenced. There were no significant
      postprandial gall-bladder volume differences between propranolol and placebo.
      CONCLUSION: Indoramin, an alpha-adrenergic antagonist, acts as a prokinetic agent
      enhancing postprandial gall-bladder emptying in patients with gall-stone disease.
      This effect is similar to its effect on postprandial gall-bladder emptying in
      healthy individuals.

PMID- 17556906
TI  - Risk factors for acute suppurative cholangitis caused by bile duct stones.
AB  - OBJECTIVE: Acute suppurative cholangitis is fatal unless adequate biliary
      drainage is obtained in a timely manner. The major cause of acute suppurative
      cholangitis is bile duct stones, but it is not known which patients with bile
      duct stones are likely to develop acute suppurative cholangitis. METHODS: Between
      May 1994 and December 2005, 343 consecutive patients with bile duct stones were
      referred to our department. Of these, 38 patients presented with acute
      suppurative cholangitis. A nasobiliary catheter or biliary stent was emergently
      inserted endoscopically to control acute suppurative cholangitis in those
      patients. Risk factors for the development of acute suppurative cholangitis in
      the 343 patients were investigated using univariate and multivariate analyses.
      RESULTS: A nasobiliary catheter or stent was inserted endoscopically in all 38
      patients with acute suppurative cholangitis. Although biliary drainage was
      considered to be effective in all patients, two patients (5.3%) died of
      deteriorating comorbid diseases despite subsiding cholangitis. In the univariate
      analysis, age >or=70 years, neurological disease, and peripapillary diverticulum
      were identified as risk factors for the development of acute suppurative
      cholangitis. In the multivariate analysis, these three factors remained
      significant. CONCLUSIONS: Advanced age, comorbid neurological disease, and
      peripapillary diverticulum were identified as independent risk factors for the
      development of acute suppurative cholangitis in patients with bile duct stones.

PMID- 17556907
TI  - Intestinal gas in plain abdominal radiographs does not correlate with symptoms
      after lactulose challenge.
AB  - OBSERVATION: Intestinal gas production and abdominal discomfort can be triggered
      by the ingestion of carbohydrates such as lactulose. Using plain abdominal
      radiographs, we studied whether subjective complaints after a lactulose breath
      test would be quantitatively related to intestinal gas volumes. METHODS:
      Abdominal symptoms after the breath test were quantified by a written
      questionnaire and gas volumes were scored in plain abdominal radiographs, in 50
      consecutive patients with unexplained, irritable bowel syndrome-like symptoms.
      Breath excretion of hydrogen and methane was determined in all patients. RESULTS:
      Forty-two (84%) of the patients claimed that their post-breath test symptoms were
      a true replicate of their customary discomfort. Total symptom scores (sum of
      scores for pain/discomfort, borborygmi, bloating, diarrhea, constipation) or any
      specific symptom score were not significantly correlated to gas volume scores (r=
      0.04; P=0.8 for total symptom score). The 13 (26%) methane producers had
      significantly higher mean gas volume scores compared with nonproducers (0.38 vs.
      0.24; P=0.0008), but fewer symptoms (total symptom score 11.9 vs. 18.2; P=0.17).
      CONCLUSION: Intestinal gas volume, as scored in plain abdominal radiographs, is
      not correlated with abdominal discomfort after lactulose challenge. Intestinal
      gas may not be the major cause of abdominal discomfort following carbohydrate
      ingestion in patients with functional gut disorders.

PMID- 17556908
TI  - Small bowel tuberculosis diagnosed by the combination of video capsule endoscopy
      and double balloon enteroscopy.
AB  - Small bowel tuberculosis is sometimes encountered in oriental countries, and
      because its symptoms are vague and present a nonspecific pattern, confirmative
      diagnosis is difficult to achieve. In 2001, two new innovative endoscopic
      techniques for the small bowel, video capsule endoscopy and double balloon
      enteroscopy, were introduced, thus advancing the diagnostic technology for small
      bowel disorders. Our asymptomatic patient with small bowel tuberculosis was
      diagnosed definitively using the combination of video capsule endoscopy and
      double balloon enteroscopy. The number of such cases will increase when those
      procedures become more widely used. At present, the endoscopic view of small
      bowel tuberculosis is difficult to differentiate from Crohn's disease and drug
      induced enteropathy, but from now on it will be possible to distinguish them
      utilizing endoscopic and fluoroscopic images. On the basis of the characteristics
      of small bowel tuberculosis with its endoscopic images, referring to our case
      report and previous literature, we report a topical diagnostic procedure, the
      combination of video capsule endoscopy and double balloon enteroscopy.

PMID- 17556909
TI  - Bortezomib-induced paralytic ileus is a potential gastrointestinal side effect of
      this first-in-class anticancer proteasome inhibitor.
AB  - Bortezomib is the first anticancer proteasome inhibitor introduced into clinical
      practice. It has been recently approved for the treatment of multiple myeloma, an
      incurable plasma cell tumour that accounts for 10-15% of all haematologic
      malignancies and for approximately 20% of deaths. Gastrointestinal toxicity
      associated with the use of this drug is common but generally mild to moderate.
      Paralytic ileus in patients undergoing bortezomib treatment has been reported,
      although a definite attribution to bortezomib administration has not been
      established. We report a myeloma patient who developed severe paralytic ileus
      during bortezomib therapy, which presented in the context of progressive
      constipation without other known causes and which regressed promptly with medical
      management after drug cessation, suggesting a direct causal relationship.
      Awareness of the various potential gastrointestinal toxic effects of bortezomib
      is of relevance given the growing number of patients undergoing treatment with
      this important and effective new cancer drug.

PMID- 17556910
TI  - Cutaneous amyloidosis associated with primary biliary cirrhosis.
AB  - Primary cutaneous amyloidosis is defined as the deposition of amyloid in the skin
      in the absence of systemic involvement. The association between primary cutaneous
      amyloidosis and other diseases, although rare, has been documented for connective
      tissue disorders such as systemic sclerosis, systemic lupus erythematosus and
      rheumatoid arthritis. We report the case of a 41-year-old woman who developed
      primary biliary cirrhosis in association with primary cutaneous amyloidosis. This
      association has not been reported before in the literature.

PMID- 17556911
TI  - Haematogenous metastasis to ascending colon in a patient with hepatocellular
      carcinoma and autoimmune hepatitis.
AB  - The association of hepatocellular carcinoma with chronic active autoimmune
      hepatitis and haematogenous metastasis to ascending colon has not been reported
      previously in the literature. The patient was asymptomatic for colonic disease
      and the finding of colonic involvement was incidental on scans subsequently
      confirmed by colonoscopy. Usually hepatocellular tumour mass would involve the
      colon by direct contiguity. Owing to haematogenous metastasis, which is extremely
      rare, the colonic mass was discontiguous from hepatic tumour lesions. The unique
      presentation of this case and the differential diagnosis of hepatic tumours
      coexisting with colonic tumours are highlighted in this case report.

PMID- 17556912
TI  - Is coca-cola effective for dissolving phytobezoars?

PMID- 17556913
TI  - Emergency splenic artery embolization in the treatment of massive bleeding
      gastric varices.

PMID- 17556918
TI  - Emergency management: expanding the disaster plan.
AB  - A comprehensive emergency management plan (CEMP) is key to minimizing the
      disruption of patient care and services during and after a natural or man-made
      disaster. The home health nurse can play a key role in enhancing, expanding, and
      evaluating the effectiveness of the organization's disaster plan. The components
      of a CEMP and lessons learned from actual implementation of disaster plans in
      home care are addressed. The disasters and emergencies of the past few years,
      such as threats of terrorism, hurricanes, floods, wildfires, tornadoes, and
      earthquakes, have validated the need to extend the emergency preparedness plan to
      a more comprehensive approach to emergency management. Communities, healthcare
      providers, and individuals/families all have been urged to take a more
      comprehensive look at their readiness for these types of events. Home healthcare
      organizations, including home health agencies, hospice providers, infusion
      providers, and medical equipment companies, can take a fresh and comprehensive
      look at their emergency management plan.

PMID- 17556917
TI  - A home care wound care challenge: its rewards, inspiration, and positive
      outcomes.
AB  - Quite often, home health team members are presented with a challenge to provide
      management for a patient who has undergone a complex gastrointestinal surgery. An
      appropriate plan of care includes the incision, wound, and colostomy care, as
      well as the psychosocial support, time management, and cost issues. Many times
      this requires ingenuity and flexibility on the part of the home care team.
      Comorbidities often increase the acuity of the nursing care as well. In any case
      and no matter how difficult the circumstances, the goal for the patient's plan of
      care is to achieve an optimal outcome that will encourage independence and a
      feeling of self-worth.

PMID- 17556919
TI  - A patient classification system for emergency events in home care.
AB  - The purpose of this article is to describe the development of a uniform
      classification system that provides a way for home care agencies to classify
      patient priority needs for evacuation, transport, supportive care, and use of
      staffing resources in an emergency/disaster situation/bioterroristic event.

PMID- 17556921
TI  - Health assessment of the very old person at home.
AB  - Home health clinicians are adept at performing comprehensive histories and
      physical examinations. The very nature of home care requires that clinicians
      assess the whole person. In fact, the Outcomes Assessment Information Data Set
      (OASIS) demands a detailed evaluation of past and current medical status. As more
      people are living into their eighties and beyond, home health clinicians are
      finding themselves assessing patients who present with signs and symptoms that
      may be specific to very old persons. This article discusses age-related changes
      in the very old patient and attempts to help clinicians differentiate abnormal
      findings and make critical decisions regarding whether intervention is needed.
      This article assumes that the reader is well versed in basic health assessment
      and focuses on specifics related to the assessment of the very old patient living
      at home.

PMID- 17556923
TI  - Medicare prospective payment before and after implementation: a review of visits
      and physical performance among Medicare home health patients after total knee
      replacements.
AB  - This retrospective case study examined whether the Medicare Prospective Payment
      System affected the number of visits and physical performance among Medicare home
      health patients after total knee replacements. Post-Prospective Payment System
      significant results included fewer visits, less improvement in knee extension
      range of motion, and increased ambulation distances at discharge.

PMID- 17556924
TI  - Where we have been and where we are going: implications for home health.

PMID- 17556925
TI  - Caring for patients of diverse religious traditions: Islam, a way of life for
      Muslims.
AB  - You have been a nurse for many years, yet you have never cared for a patient who
      practices Islam until now. You are assigned to a Muslim family for a home visit.
      What aspects about Muslim beliefs and way of life might be helpful to know before
      your visit?

PMID- 17556926
TI  - New VNAA head promises to be a forceful advocate for safety net providers.
      Interview by Maria McGonagle.

PMID- 17556928
TI  - Proceedings of the 12th Annual San Antonio Trauma Symposium, September 19-21,
      2006, San Antonio, Texas, USA.

PMID- 17556927
TI  - "You sure do ask a lot of nosy questions!".

PMID- 17556929
TI  - Acute brain injury survivor's management.

PMID- 17556931
TI  - Neuro-Critical care in modern war.

PMID- 17556932
TI  - Lessons learned from OIF: a neurosurgical perspective.

PMID- 17556933
TI  - Anesthesiology.

PMID- 17556934
TI  - Monitoring trauma patients.

PMID- 17556935
TI  - Methods of hemodynamic monitoring.

PMID- 17556936
TI  - Impact of emergency medicine specialists in tactical pre-hospital and en route
      care: what does the available data say?

PMID- 17556937
TI  - The pregnant trauma patient.

PMID- 17556940
TI  - Combat trauma training for current casualty care.

PMID- 17556941
TI  - Hemorrhage control research on today's battlefield: lessons applied.

PMID- 17556943
TI  - Civil sector tactical ems.

PMID- 17556942
TI  - Panel synopsis: pre-hospital combat health support 2010: what should our azimuth
      be?

PMID- 17556944
TI  - Army/Navy: it really does work.

PMID- 17556945
TI  - Experience at the 332nd Air Force Theater Hospital: evacuation hub for Iraq.

PMID- 17556946
TI  - Eye trauma management--OIF clinical considerations.

PMID- 17556947
TI  - Removal of unexploded ordnance.

PMID- 17556948
TI  - Thermal injuries in operations Iraqi and enduring freedom (OIF and OEF).

PMID- 17556949
TI  - Endovascular approaches for traumatic thoracic aortic injury: immediate versus
      delayed therapy.

PMID- 17556950
TI  - Operative approaches for traumatic thoracic aortic injury: immediate versus
      delayed therapy.

PMID- 17556951
TI  - Splenic injury: angio vs. operation.

PMID- 17556952
TI  - Splenic injury: angiogram vs. operation.

PMID- 17556954
TI  - What is the standard approach to temporary abdominal closure?

PMID- 17556953
TI  - Focused assessment with sonography for trauma (FAST): the truth about ultrasound
      in blunt trauma.

PMID- 17556956
TI  - Unstable pelvic fractures: the use of angiography in controlling arterial
      hemorrhage.

PMID- 17556957
TI  - Butt binder.

PMID- 17556958
TI  - Cervical spine clearance in the obtunded patient: it takes more than a simple CT.

PMID- 17556960
TI  - Critical care aeromedical teams (Ccatt): then, now and what's next.

PMID- 17556961
TI  - Damage control resuscitation.

PMID- 17556962
TI  - Things that go boom: injuries from explosives.

PMID- 17556963
TI  - Mass casualties in combat: lessons learned.

PMID- 17556964
TI  - Simplified reconstruction of traumatic posterior urethral defects.

PMID- 17556965
TI  - The current spectrum of battlefield urological injuries.

PMID- 17556966
TI  - Trauma system and prevention summary for trauma systems.

PMID- 17556967
TI  - Alcohol and injury: American College of Surgeons Committee on trauma requirements
      for trauma center intervention.

PMID- 17556969
TI  - Injury prevention: why so important?

PMID- 17556970
TI  - Preventing motor vehicle crashes (no accidents please!).

PMID- 17556971
TI  - Trauma systems and access to emergency medical care.

PMID- 17556973
TI  - Infection control challenges related to war wound infections in the ICU setting.

PMID- 17556974
TI  - Trauma and the immune response: strategies for success.

PMID- 17556975
TI  - Potential benefit of vasopressin in resuscitation of hemorrhagic shock.

PMID- 17556976
TI  - Acute respiratory distress syndrome in trauma patients.

PMID- 17556977
TI  - Osteomyelitis.

PMID- 17556978
TI  - Clinical application of advanced prosthetic technology: an update.

PMID- 17556979
TI  - Geriatric spine fractures: an emerging healthcare crisis.

PMID- 17556980
TI  - Improving results in posterior wall acetabular fracture surgery.

PMID- 17556981
TI  - Casualty evacuations: transport of the severely injured.

PMID- 17556983
TI  - Modern burn care.

PMID- 17556984
TI  - Planning for burn mass casualty incidents.

PMID- 17556985
TI  - The basis of fibrosis and wound healing disorders following thermal injury.

PMID- 17556986
TI  - Therapeutic options for neuropathic pain.

PMID- 17556987
TI  - Burn care in Iraq.

PMID- 17556988
TI  - Emerging advances in burn resuscitation.

PMID- 17556989
TI  - Infections in burns.

PMID- 17556990
TI  - Aeromedical evacuation of burn patients from Iraq.

PMID- 17556991
TI  - The role of the advanced practice nurse within the continuum of trauma care.

PMID- 17556992
TI  - Forensics in the hospital setting: what everyone touching the patient should
      know.

PMID- 17556993
TI  - Trauma nursing.

PMID- 17556994
TI  - Exemption of informed consent (final rule): procedures for critical trauma
      studies.

PMID- 17556995
TI  - Burn scar and contracture management.

PMID- 17556996
TI  - Prehospital assessment and treatment of thoracic injuries.

PMID- 17556998
TI  - Damage control mechanical ventilation: ventilator induced lung injury and lung
      protective strategies in children.

PMID- 17556999
TI  - Monitoring the critically ill or injured child.

PMID- 17557001
TI  - Materials for orbital reconstruction.

PMID- 17557002
TI  - Gunshot wounds to the face.

PMID- 17557003
TI  - Panel synopsis discussion on facial trauma.

PMID- 17557004
TI  - Management of facial fractures in the deployed american soldier.

PMID- 17557005
TI  - Acute spinal cord injury management.

PMID- 17557006
TI  - Management of soft tissue defect.

PMID- 17557007
TI  - Management of frontal sinus fractures.

PMID- 17557009
TI  - The National Disaster Life Support Foundation: local preparedness, global
      response.

PMID- 17557010
TI  - Regional medical disaster planning: an integrated approach to ESF-8 planning.

PMID- 17557011
TI  - Medical field hospital capability and trauma care.

PMID- 17557012
TI  - Pandemic influenza: what does it mean for us?

PMID- 17557013
TI  - Worldwide initiative celebrates women's health.

PMID- 17557014
TI  - Prevent shingles with Zostavax.

PMID- 17557015
TI  - A little altruism can hone your leadership skills.

PMID- 17557016
TI  - Understanding mammogram microcalcifications.

PMID- 17557017
TI  - Billing for NP provider services: updates on coding regulations.

PMID- 17557021
TI  - Osteoporosis detection: is BMD testing the future?

PMID- 17557023
TI  - Strategies for contraceptive success.

PMID- 17557025
TI  - Rural women find support online.

PMID- 17557026
TI  - Chlamydia screening in teenage girls.

PMID- 17557027
TI  - Get optimum outcomes for acute pancreatitis patients.

PMID- 17557028
TI  - Stenting fights carotid disease.

PMID- 17557029
TI  - CVD risk factors in rural women.

PMID- 17557032
TI  - Plasma levels of adrenomedullin, a vasoactive peptide, in type 2 diabetic
      patients with and without retinopathy.
AB  - AIM: The aim of this study was to investigate whether adrenomedullin (AM)
      secretion is modified in type 2 diabetic patients with and without retinopathy.
      METHODS: The study was performed on 92 patients with type 2 diabetes, 65 of whom
      had uncomplicated diabetes, 27 had retinopathy, and 40 had mild to moderate
      hypertension. Patients with serum creatinine levels >1.2 mg/dL, were excluded.
      Circulating AM was assayed using a specific radioimmunoassay. RESULTS: AM
      concentrations were significantly higher in type 2 diabetic patients (25+/-2.1
      pg/mL) than in the 31 normal subjects (11+/-0.8 pg/mL) (P<0.001). Type 2 diabetic
      patients with retinopathy had significantly greater AM levels (30.8+/-3.4 pg/mL)
      than both controls (P<0.001) and type 2 diabetic patients without retinopathy
      (25.2+/-2 pg/mL same as previous value) (P<0.001). No statistical difference was
      found between diabetic patients with pre-proliferative retinopathy (27.3+/-4.7
      pg/mL) and proliferative retinopathy (24+/-3.1 pg/mL) (P=0.543). In type 2
      diabetic patients, a significant correlation between plasma AM levels and HbA1c
      values (r=0.467; P<0.01) was found. CONCLUSION: Our findings indicate that
      circulating AM is increased in type 2 diabetic patients and that increase
      correlates with poor glucose metabolic control and presence of retinopathy.

PMID- 17557033
TI  - Clinical and laboratory features greatly overlap in patients with
      macroprolactinemia or monomeric hyperprolactinemia.
AB  - AIM: The aim of this study was to evaluate the clinical and laboratory features
      of 64 patients with macroprolactinemia and to compare them to those of
      individuals with monomeric hyperprolactinemia. METHODS: The study included 64
      patients (54 women and 10 men) with macroprolactinemia and 96 patients (70 women
      and 26 men) with monomeric hyperprolactinemia (32 with prolactinomas). RESULTS:
      Symptoms related to prolactin (PRL) excess were found in about 44% of individuals
      from the macroprolactinemia group and in 88.5% of patients with monomeric
      hyperprolactinemia (P<0.0001). However, the frequency of menstrual disturbances
      (oligomenorrhea or amenorrhea), galactorrhea and erectile dysfunction did not
      differ in both groups. In contrast, the association of galactorrhea and menstrual
      disturbances was significantly more prevalent in women with monomeric
      hyperprolactinemia. Although mean PRL levels were higher in patients with
      monomeric hyperprolactinemia (565.9+/-2726.4 vs 113.3+/-94.5 ng/mL, P<0.001),
      there was a great overlap between both groups. Among macroprolactinemic patients,
      pituitary magnetic resonance imaging revealed an image suggestive of a
      microadenoma in 7 (10.9%) and a macroadenoma in 1 (1.6%). Normalization of PRL
      levels during therapy with dopamine agonists was significantly more frequent in
      patients with monomeric hyperprolactinemia than in subjects with
      macroprolactinemia (78.6% vs 32%, P=0.0006). CONCLUSION: Our data show that
      symptoms related to PRL excess are frequently found in subjects with
      macroprolactinemia. Moreover, no clinical or laboratory features could reliably
      differentiate macroprolactinemic patients from those with monomeric
      hyperprolactinemia. Therefore, the screening for macroprolactin should not be
      restricted to asymptomatic patients.

PMID- 17557034
TI  - Neuroprotective effects of estrogen and selective estrogen receptor modulators
      begin at the plasma membrane.
AB  - Estrogen is neuroprotective in a large number of models in vivo and in vitro. Its
      application in hormone replacement therapy has proven to be more complicated,
      necessitating better understanding of how estrogen signals in the brain. Estrogen
      binds to estrogen receptors to regulate gene transcription, and activates a
      number of rapid signaling cascades from the plasma membrane. These rapid
      signaling cascades have been shown to play important roles in mediating the
      neuroprotective effects of estrogen. This review covers evidence that
      understanding and targeting the membrane effects of estrogen has emerged as an
      important area in the design of novel neuroprotective drugs.

PMID- 17557035
TI  - Progestins and neuroprotection: are all progestins created equal?
AB  - Our understanding of the biology of gonadal steroids has expanded such that we
      now appreciate that the effects of gonadal steroid hormones, including estradiol
      and progesterone, extend beyond the strict confines of reproductive function and
      exert their effects on a wide range of tissue targets including, but not limited
      to, the bone, the heart and the brain. With respect to the brain, an increasing
      body of literature supports the protective effects of estradiol and progesterone.
      However, results from the Women's Health Initiative (WHI) underscored the fact
      that there may be important caveats to these protective effects and include the
      choice of hormone used. Here, we describe our current understanding of the
      neurobiology of progesterone and the synthetic progestin used in most
      formulations of hormone therapy, medroxyprogesterone acetate, and provide a
      review of the basic and clinical literature that address the importance of
      progestins in neuroprotection. In addition, we caution that the effects and
      mechanisms underlying the neurobiological effects of progestins may not be
      identical to those seen in non central nervous systems. And though additional
      research is certainly needed to explore the neurobiology of progesterone and its
      related progestins more completely, we provide evidence that, at least with
      respect to the brain, not all progestins are created equal.

PMID- 17557036
TI  - Protective and regenerative effects of the GH/IGF-I axis on the brain.
AB  - Apart from regulating somatic growth and metabolism, evidence suggest that the
      GH/ IGF-I axis is involved in the regulation of brain growth, development and
      myelination. Moreover, growth hormone (GH) and particularly IGF-I have been
      attributed neuroprotective effects in different in vitro and in vivo experimental
      models. In addition, both GH and IGF-I affect cognition and biochemistry in the
      adult brain. Some of the effects of GH are suggested to be mediated by
      circulating IGF-I, while other effects may be due to locally produced IGF-I
      within the brain. It is also possible that GH may act directly on the central
      nervous system (CNS) without involving IGF-I (either circulating or locally).
      Plasticity in the CNS may be viewed as changes in the functional interplay
      between the major cell types neurons, astrocytes and oligodendrocytes. GH and IGF
      I affect all these cell types in several aspects. Apart from neuroprotective
      effects of GH and IGF-I in different experimental models of CNS injury, IGF-I has
      been found to increase progenitor cell proliferation and new neurons,
      oligodendrocytes, and blood vessels in the dentate gyrus of the hippocampus. In
      the adult cerebral cortex, it appears that only oligodendrogenesis is affected.
      The increase of IGF-I on endothelial cell phenotype may explain the increase in
      cerebral arteriole density observed after GH treatment. In the present review,
      different aspects of the GH/IGF-I axis effects on the brain will be discussed
      with particular emphasis on neuroprotection, regeneration and brain plasticity.
      Moreover, recent findings describing neuroprotective effects and effects on
      synaptic plasticity by GH secretagogues will be reviewed.

PMID- 17557037
TI  - Spermiogram: techniques, interpretation, and prognostic value of results.
AB  - The ejaculate specimen represents an output derived from the efficiency of three
      essential biological events: testicular production of sperm, progression and
      maturation of testicular sperm through epididymides, neurophysiological integrity
      of the mechanisms leading to the final process of ejaculation. All three events
      can negatively be affected by temporary conditions in the three months up to
      seminal analysis (temperature, temporary/seasonal exposure to chemical
      substances; extended use of medicines), and so it will be negatively influenced
      by chronic internal conditions (diabetes, chronic liver or kidney diseases,
      colopathy, etc.) that will be appropriate to call again in the patient's history
      (anamnesis). In a diagnostic, level-based model of care, a standard semen
      analysis is a first level procedure (including clinical history, physical general
      and focused examination, semen analysis) to be performed only when male
      infertility is suspected, with few or without initial specific clinical
      indications. Beyond the limits of semen analysis, the test may be useful for the
      specialist (and also to the patient!) and reliable. The reliability of the semen
      analysis is linked to whether it is done according to the recommendations and the
      codified techniques of the World Health Organization (WHO) standard manual
      (fourth revised edition 1999). A standard semen analysis includes three operative
      stages: preanalytic phase; analytic phase; postanalytic phase.

PMID- 17557038
TI  - Some critical points about the metabolic syndrome.

PMID- 17557039
TI  - Combination therapy with symbiotics and local anti-inflammatories for red
      anusitis.
AB  - AIM: The aim of this study was to compare red anusitis treatment with topical
      mesalazine alone versus combined treatment with mesalazine plus a symbiotic (zir
      fos(R), Alfa Wassermann) to determine whether the effect of a therapy combining
      anti-inflammatory activity with a symbiotic that interferes with intestinal
      dysbiosis can improve anusitis symptoms. METHODS: From May 2004 to December 2005,
      24 patients (14 male, 10 female; mean age 46.3 years, range 28-67) with
      idiopathic red anusitis, without other colo-proctologic diseases, were enrolled
      in a double blind study on the effect of topical mesalazine alone versus combined
      mesalazine plus symbiotic treatment. RESULTS: In the mesalazine monotherapy
      group, reduction in pain, hyperemia and bleeding was transient and symptoms
      recurred 1 year after discontinuation of treatment (mean visual analogue scale
      [VAS] scores: pain 3.1; hyperemia 2; bleeding 2.5. In the combined treatment
      group, a significant improvement in symptoms was noted (mean VAS scores: pain
      1.5; hyperemia 0.5; bleeding 0) at 1 month after discontinuation of treatment.
      CONCLUSION: The results showed a greater long-term benefit of combination therapy
      mesalazine plus symbiotic (zir fos) in the treatment of red anusitis than with
      topical mesalazine alone, particularly for pain and bleeding. Further studies on
      larger series investigating additional subjective and objective variables are
      needed to confirm these findings.

PMID- 17557040
TI  - A 2007 panorama on gastro-esophageal reflux disease.

PMID- 17557041
TI  - Nonerosive reflux disease.
AB  - Nonerosive reflux disease (NERD) is the most common phenotype of gastroesophageal
      reflux disease. By definition, patients with NERD have typical reflux symptoms
      caused by the intraesophageal reflux of gastric contents but have no visible
      esophageal mucosal injury. This is in contrast to patients with erosive reflux
      disease (ERD) or Barrett's esophagus (BE) who have obvious esophageal mucosal
      injury on endosco-py. Only 50% of patients with NERD have pathologic esophageal
      acid exposure as detected on 24-h pH monitoring. NERD patients with physiologic
      esophageal acid exposure and good temporal correlation of symptoms with reflux
      events are considered to have esophageal hypersensitivity, while patients with no
      symptom-reflux correlation are considered to have functional heartburn. It is
      possible yet uncommon for NERD to progress to severe ERD (i.e. LA Grade C or D)
      or BE. Patients with NERD and pathologic esophageal acid exposure have motor
      dysfunction and acid reflux abnormalities that are similar to patients with ERD
      and BE, whereas NERD patients with physiologic esophageal acid exposure have
      minimal abnormalities and are not much different than healthy controls. The
      pathological feature most indicative of NERD is the presence of dilated
      intercellular spaces within squamous epithelium, an ultrastructural abnormality
      readily identified on transmission electron microscopy but also on light
      microscopy. A symptomatic response to an empiric trial of high-dose proton pump
      inhibitor (PPI) therapy is a simple and useful strategy to establish the
      diagnosis of NERD, although histology and pH monitoring may be useful in
      confirming the diagnosis. Patients with NERD suffer similar decrements in quality
      of life as do patients with erosive esophagitis. Therapy is aimed at eliminating
      or reducing symptoms and improving quality of life. PPIs are the most effective
      agents for the treatment of NERD although they are less effective in providing
      symptom relief than in patients with erosive esophagitis. Laparoscopic antireflux
      surgery is an effective therapy for selected patients with NERD and outcomes are
      better when performed in high volume centers.

PMID- 17557042
TI  - The diagnosis of gastroesophageal reflux disease.
AB  - Gastroesophageal reflux disease (GERD) is known to cause erosive esophagitis,
      Barrett esophagus and has been linked to the development of adenocarcinoma of the
      esophagus. Currently, endoscopy is the main clinical tool for visualizing
      esophageal lesions, but the majority of GERD patients do not have endoscopic
      visible lesions and other methods are required. Ambulatory esophageal pH
      monitoring is the gold standard in diagnosing GERD, since it measures distal
      esophageal acid exposure and demonstrates the relationship between symptoms and
      acid reflux. The effectiveness of selective gastric acid suppressive therapy led
      to the introduction of short trials of proton pump inhibitors (PPIs) to diagnose
      GERD and they are often used as a first line diagnostic tool in clinical practice
      and, in particular, in the primary care setting, the current trend being that
      gastroenterologists are asked to evaluate mainly patients with persistent GERD
      symptoms while on PPI therapy. In these patients the question is whether the
      persistent symptoms are or not associated with reflux (acid or nonacid).
      Recently, either combined multichannel intraluminal impedance and pH monitoring
      or bilimetry allow to study the mechanisms underlying the persistent symptoms on
      acid suppressive therapy. Manometry is mandatory prior to any surgical approach
      and to verify motility disorders that could be associated to GERD.

PMID- 17557043
TI  - [Helicobacter pylori and gastro-esophageal reflux disease: clinical
      considerations].
AB  - In the last decade, several studies have approached the issue of a potential
      relationship between Helicobacter pylori (H. pylori) infection and gastro
      esophageal reflux disease (GERD). The different aspects debated were the
      possibility that the bacterium could have a protective role or worsen the disease
      or have no relationship at all. Hitherto, although some researchers have proposed
      fascinating pathogenic pathways, no scientific evidences exist to support the
      need to treat or not H. pylori infection in order to modify the natural history
      of GERD. In this review, the authors report the main updated considerations
      regarding this matter.

PMID- 17557044
TI  - Esophageal adenocarcinoma and Barrett's esophagus.
AB  - Esophageal adenocarcinoma (EAC) is the most rapidly rising incidence cancer
      associated with a poor 5-year survival rate. Barrett's esophagus (BE) is a well
      established premalignant condition for the development of EAC and hence it is
      imperative that patients with BE or at risk for developing BE should be
      identified and managed appropriately. The endoscopic recognition of BE should
      include the assessment of the circumferential (C) and maximum (M) extent of the
      endoscopically visualized BE segment as well as endocsopic landmarks (The Prague
      C&M criteria). Although controversial, clinical strategies of screening and
      surveillance have focused on identification of esophageal neoplasia at an early
      asymptomatic and curable stage with the ultimate goal of preventing deaths from
      this cancer. Risk stratification that involves screening and surveillance of high
      risk individuals may improve the efficacy and effectiveness of these programs.
      The future of this endeavor lies in the identification and validation of
      biomarkers coupled with enhanced endoscopic techniques such as narrow band
      imaging, autofluorescence imaging, confocal laser endomicroscopy etc. Endoscopic
      therapies (endoscopic mucosal resection, ablative therapies) have become
      attractive alternatives for the treatment of high grade dysplasia and/or early
      EAC in BE patients. The main stays of treatment of advanced cancers are debulking
      surgery, chemotherapy, radiotherapy and palliative care measures.

PMID- 17557045
TI  - Gastroesophageal reflux and its possible role in the pathogenesis of upper
      aerodigestive tract disorders.
AB  - Associations have been reported between gastroesophageal reflux (GER) and a
      variety of upper and lower respiratory tract conditions. Respiratory conditions
      and GER are common and would be expected to coexist in many patients. Whether
      there is a relationship between GER and these conditions, its nature still remain
      controversial, the data available are frequently conflicting and furthermore the
      direct association between symptoms and reflux is often difficult to establish.
      For this reason, the majority of clinicians still treat extraesophageal
      manifestations of GER empirically as esophageal pH testing is not routinely used
      in the ear, nose and throat (ENT) practice. Purpose of this paper is to examine
      the relationship between GER and these conditions both in adults and children,
      through a PubMed database systematic review.

PMID- 17557046
TI  - Laryngeal disorders in patients with gastroesophageal reflux disease.
AB  - Gastroesophageal reflux disease (GERD) is a common medical condition affecting
      approximately 35-40% of the adult population in the western world. Chronic
      laryngeal signs and symptoms associated with GERD are often referred to as reflux
      laryngitis or laryngopharyngeal reflux (LPR). It is estimated that up to 15% of
      all visits to the otolaryngology offices are because of manifestations of LPR.
      Injury may occur as a result of one or chronic reflux of gastroduodenal contents
      directly injuring the laryngeal mucosa. Since less amount of acid is required to
      make the injury to the larynx as compared to injury to esophagus; it is believed
      that intermittent exposure to small amount of gastric content can result in
      laryngitis. The most common presenting symptoms of LPR include hoarseness, sore
      throat, throat clearing, and chronic cough. The diagnosis of LPR is usually made
      on the basis of presenting symptoms and associated laryngeal signs including
      laryngeal edema and erythema. Current recommendation for management of this group
      of patients is empiric therapy with twice daily proton-pump inhibitors for 2 to 4
      months. In majority of those who are unresponsive to such therapy other causes of
      laryngeal irritation is considered. Surgical fundoplication is most effective in
      those who are responsive to acid suppressive therapy.

PMID- 17557047
TI  - Endoscopic antireflux repairs.
AB  - The high prevalence of gastroesophageal reflux disease (GERD) in the Western
      societies has accelerated the need for new modalities of treatment. Currently,
      medical and surgical therapies are widely accepted among patients and physicians.
      New potent antisecretory drugs and the development of minimally invasive surgery
      for the management of reflux are at present the pivotal and largely accepted
      approaches to treatment. The minimally invasive treatment revolution, however,
      has stimulated several new endoscopic techniques. At present, the data is limited
      and further studies are necessary to compare the advantages and disadvantages of
      the various endoscopic techniques to medical and laparoscopic management of GERD.
      Further trials and device refinements will assist clinicians. In this article, we
      present an overview of the various techniques that are currently in practice and
      under study. We report the efficiency and durability of various endoscopic
      therapies for GERD. The potential for widespread use of these techniques will
      also be discussed. Articles and abstracts published in English on this topic were
      retrieved from Pubmed. Due to limited number of studies and various trials,
      strict criteria were not used for the pooled data presented, however, an effort
      was made to avoid bias by including only studies that used off-PPI scoring as
      baseline and intent to treat.

PMID- 17557048
TI  - Chronic abdominal pain associated with intermittent compression of the celiac
      artery.
AB  - Recurrent abdominal pain (RAP), surely one of the most frequent causes of medical
      intervention, is frequently present in many gastrointestinal disease. Usually no
      structural and/or biochemical alterations can be demonstrated. This condition is,
      therefore, considered to be due to functional disorders such as irritable bowel
      syndrome (IBS) or functional dyspepsia. Previous observations suggest the
      presence of a rare alteration of celiac vessels among the possible causes of RAP.
      This pathological condition was known as Dunbar syndrome. We report 2 cases of
      chronic abdominal pain. The former reported weight loss and the latter anemia
      with iron deficiency. It is remarkable that patients with initial diagnosis of
      IBS can be affected by celiac disease (CD), which is the cause of their abdominal
      pain. Our patients were tested for CD; the former was negative and IBS was
      diagnosed, the latter was positive and a gluten free diet was prescribed. The
      presence of an epigastric bruit, accentuated during expiration, suggested a
      possible vascular alteration known as tripod celiac artery compression syndrome.
      Duplex Doppler sonography suggests the diagnosis of celiac arterial constriction
      due the diaphragmatic ligament. These cases show that tripod celiac artery
      compression syndrome might be a cause of RAP and that it may be evaluated and
      investigated when the clinical examination discloses an abdominal systolic bruit.

PMID- 17557049
TI  - Slow component of VO(2) during level and uphill treadmill running: relationship
      to aerobic fitness in endurance runners.
AB  - AIM: The aim of this study was to compare the oxygen uptake (VO(2)) slow
      component (SC) during level and uphill running in endurance runners, and to
      identify associations between the SC and the following aerobic fitness
      indicators: peak VO(2), running speed associated with the peak VO(2) (Vpeak),
      running speed at the lactic threshold and the VO(2) fraction elicited at the
      lactic threshold. METHODS: Fourteen male endurance-trained runners underwent
      several 6-min bouts of level (LTR) and 10.5% uphill treadmill running. VO(2) SC
      was calculated as the difference between mean VO(2) during the 6th and the 3rd
      minutes. RESULTS: The highest mean values for the SC were 181.9+/-240.2 mL x min(
      1) for level running at approximately 94% peak VO(2)2 and 105.4+/-154.6 mL x min(
      1) for uphill running at approximately 90% peak VO(2). The SC observed during the
      last bout of the LTR correlated with peak VO(2) and with Vpeak (-0.71 and -0.76,
      P<0.05, respectively). CONCLUSION: The results show that for endurance-trained
      runners the magnitude of the SC is not affected by the treadmill gradient and
      that within a homogeneous sample of endurance-trained runners the SC does not
      correlate with indicators of aerobic fitness.

PMID- 17557050
TI  - Relationships between maximal anaerobic power of the arms and legs and javelin
      performance.
AB  - AIM: The aim of this study was to examine relationships between maximal anaerobic
      power, as measured by leg and arm force-velocity tests, estimates of local muscle
      volume and javelin performance. METHODS: Ten trained national level male javelin
      throwers (mean age 19.6+/- 2 years) participated in this study. Maximal anaerobic
      power, maximal force and maximal velocity were measured during leg (Wmax-L) and
      arm (Wmax-A) force-velocity tests, performed on appropriately modified forms of
      Monark cycle ergometer. Estimates of leg and arm muscle volume were made using a
      standard anthropometric kit. RESULTS: Maximal force of the leg (Fmax-L) was
      significantly correlated with estimated leg muscle volume (r=0.71, P<0.05). Wmax
      L and Wmax-A were both significantly correlated with javelin performance (r=0.76,
      P<0.01; r=0.71, P <0.05, respectively). Maximal velocity of the leg (Vmax-L) was
      also significantly correlated with throwing performance (r=0.83; P<0.001).
      CONCLUSION: Wmax of both legs and arms were significantly correlated with javelin
      performance, the closest correlation being for Wmax-L; this emphasizes the
      importance of the leg muscles in this sport. Fmax-L and Vmax-L were related to
      muscle volume and to javelin performance, respectively. Force-velocity testing
      may have value in regulating conditioning and rehabilitation in sports involving
      throwing.

PMID- 17557051
TI  - The effects of acute static stretching on reaction time and force.
AB  - AIM: The purpose of this study was to determine alterations in explosive force
      production and reaction time following the soleus and gastrocnemius muscle
      stretching. Specifically we investigated whether or not actually stretching the
      calf muscles would alter the performance of reaction time and force production.
      METHODS: Fifteen subjects (age: 25.07+/-5.35 years; height: 1.76+/-0.07 m;
      weight: 81.38+/-17.28 kg) completed 2 test sessions. All subjects underwent a
      warm-up of 5 min bicycling and stretching of the ankle plantar flexors followed
      by reaction time and force tasks, and a similar control period of no stretch of
      the ankle plantar flexors. Measure of reaction time and force were assessed
      following stretching and no stretching conditions. RESULTS: There were no
      significant differences in reaction time and force between the stretching and
      control conditions (P>0.05). CONCLUSION: These results demonstrated that 3 sets
      of 15 s duration of the static stretching did not have a positive or negative
      effect on reaction time and explosive force.

PMID- 17557052
TI  - The effect of mountain bike suspensions on vibrations and off-road uphill
      performance.
AB  - AIM: This study evaluates the effect of front suspension (FS) and dual suspension
      (DS) mountain-bike on performance and vibrations during off-road uphill riding.
      METHODS: Thirteen male cyclists (27+/-5 years, 70+/-6 kg, VO(2max)59+/-6 mL.kg(
      1).min(-1), mean+/-SD) performed, in a random sequence, at their lactate
      threshold, an off-road uphill course (1.69 km, 212 m elevation gain) with both
      type of bicycles. Variable measured: a) VO(2) consumption (K4b2 analyzer,
      Cosmed), b) power output (SRM) c) gain in altitude and d) 3-D accelerations under
      the saddle and at the wheel (Physilog, EPFL, Switzerland). Power spectral analy-
      sis (Fourier) was performed from the vertical acceleration data. RESULTS:
      Respectively for the FS and DS mountain bike: speed amounted to 7.5+/-0.7 km.h(
      1) and 7.4+/-0.8 km.h(-1), (NS), energy expenditure 1.39+/-0.16 kW and 1.38+/
      0.18, (NS), gross efficiency 0.161+/-0.013 and 0.159+/-0.013, (NS), peak
      frequency of vibration under the saddle 4.78+/-2.85 Hz and 2.27+/-0.2 Hz (P<0.01)
      and median-frequency of vertical displacements of the saddle 9.41+/-1.47 Hz and
      5.78+/-2.27 Hz (P<0.01). CONCLUSION: Vibrations at the saddle level of the DS
      bike are of low frequencies whereas those of the FS bike are mostly of high
      frequencies. In the DS bike, the torque produced by the cyclist at the pedal
      level may generate low frequency vibrations. We conclude that the DS bike absorbs
      more high frequency vibrations, is more comfortable and performs as well as the
      FS bicycle.

PMID- 17557053
TI  - Measurement of talent in volleyball: 15-month follow-up of elite adolescent
      players.
AB  - AIM: The purpose of this study was two-fold: first, to examine the contribution
      of a battery of physical and motor tests to early phases of talent detection and
      early development in volleyball, and second, to differentiate between and compare
      the motor ability of 16-year-old starter (S) and non-starter (NS) volleyball
      players. METHODS: Fifteen male adolescent volleyball players underwent assessment
      of physical and motor ability 6 times during a 15-month training program;
      however, not all of them took part in each testing phase. The battery was
      composed of 8 physical and motor tests and 2 skill tests. The physical and motor
      tests included 2 speed tests, an agility run, 4 explosive power tests, and an
      endurance test. The skill tests evaluated service accuracy at rest and following
      effort. RESULTS: All participants improved their results in all but 2 tests
      (endurance and skill tests) across testing phases. Comparisons between the S
      (n=8) and NS (n=7) revealed that only one physical explosive power test (vertical
      jump with approach), was found to be a good indicator for distinguishing between
      the 2 groups of players. CONCLUSION: It was concluded that the volleyball battery
      of tests was not sensitive enough to distinguish between the ''good'' and ''very
      good'' players suggesting that physical and motor tests do not reflect open skill
      ability in volleyball.

PMID- 17557054
TI  - Throwing effectiveness and rotational strength of the shoulder in team handball.
AB  - AIM: The purpose of this study was to examine: a) the influence of simulated game
      activities (SGA) in throwing effectiveness and rotational strength of the
      shoulder; and b) the relationship between the rotational strength of the shoulder
      and ball velocity and accuracy in team handball. METHODS: Sixteen female handball
      players participated following a SGA, which included distinctive handball
      activities for 60 min (2 halves of 30 min). For testing ball velocity and
      accuracy, every 10 min, subjects performed 3 shots on the spot towards a target
      from 7 m distance. Shoulder isokinetic strength during internal (IR) and external
      rotation (ER) was evaluated in 3 angular velocities (60, 180, and 300 degrees /s)
      before SGA, during half-time and at the end of SGA. RESULTS: Throwing
      effectiveness was significantly affected by time, as aiming accuracy was
      gradually decreased. However, ball velocity remained stable. The correlation
      between ball velocity and deviation was not significant throughout the SGA. No
      statistically significant differences between measurements were found in maximum
      isokinetic torque, except from the case of ER at 180 degrees /s, where there was
      a significant difference between initial measurement (IM) and A and B halves. A
      significant relationship between isokinetic torque and ball velocity was found
      only for the IM for ER (180, 300 degrees /s) and IR (300 degrees /s). CONCLUSION:
      The main findings of this study are that, during a game simulation, time affects
      only aiming accuracy and not ball velocity or rotational strength of the
      shoulder. Moreover, peak torque of IR and ER of the shoulder is not related with
      ball velocity and throwing effectiveness.

PMID- 17557055
TI  - Changes in heart rate and blood lactate concentration as intensity parameters
      during simulated Taekwondo competition.
AB  - AIM: The absence of studies related to physiological responses in athletes during
      Taekwondo competition makes this the first attempt to investigate the physical
      aspects of this relative new Olympic sport event. Therefore, the aim of this
      study was to record and analyze heart rate (HR) and blood lactate (BL) levels of
      elite male Taekwondo athletes during multiple competition bouts in a single day.
      METHODS:  EXPERIMENTAL DESIGN: prospective. SETTING: competition simulation.
      PARTICIPANTS: 24 elite male athletes, aged 20 to 24 years. MEASURES: HR and BL
      responses were studied on 24 national level Taekwondo players in multiple
      competition bouts to explore the aerobic-anaerobic metabolism, as well as the
      physical demands of the players. The aerobic capacity (VO(2max)) of the players
      were determined using a 20 m shuttle run test. HR and BL concentration levels
      were measured during warm up and fighting rounds in every competition bout.
      RESULTS: The mean VO(2max) ability for all subjects was 53.92 mL/kg/min and there
      was no significant difference between groups. Only the heavy weight division (+80
      kg) players demonstrated a significant higher HRmax (P<0.05) than the other two
      divisions. No inter-weight division, as well as inter-round differences, were
      observed in the HR and BL concentration levels of the players. After all
      divisions were recorded and analyzed the mean HR and BL levels during competition
      were 158 beats/min and 3.35 mmol/L, respectively. CONCLUSION: The study
      highlights that in competitive Taekwondo, irrespective of the weight division or
      aerobic capacity, the anaerobic adaptability of the subjects is the same.

PMID- 17557056
TI  - Relationship between VO(2max) and repeated sprint ability using non-motorised
      treadmill ergometry.
AB  - AIM: The aim of this study was to investigate the relationship between maximal
      oxygen uptake (Vo(2max)) and repeated sprint ability (RSA) using non-motorised
      treadmill ergometry. METHODS: Ten male participants (mean [standard deviation]
      VO(2max): 57.5 [2.1] mL x kg(-1).min(-1)) completed a RSA test (10, 6-s sprints
      with 34-s recovery) on a non-motorised treadmill. Oxygen consumption (VO(2)) and
      heart rate (HR) were measured during the RSA test and the decrement of
      performance fatigue (%(d)) was calculated for the performance indices mean
      maximal speed (MxSp) and average power output (AvPO). RESULTS: There were
      significant relationships between VO(2max) and the %(d) MxSp (r=-0.75, P<0.05)
      and VO(2max) and the %(d) AvPO (r=-0.69, P<0.05). There were also significant
      relationships between VO(2max) and HR recovery (r=0.56, P<0.05) and VO(2max) and
      VO(2) recovery (r=0.7, P<0.01). However, while no significant relationships were
      reported between HR recovery and %(d) MxSp (r= 0.45, P>0.05) and HR recovery and
      %(d) AvPO (r=-0.52, P>0.05), significant relationships were observed between
      VO(2) recovery and %(d) MxSp (r=-0.75, P<0.05) and between VO(2) recovery and
      %(d) AvPO (r=-0.77, P<0.05). CONCLUSION: The findings of this study suggest that
      VO(2max) may be an important factor determining RSA during repeated, high
      intensity running-based exercise, such as field hockey, rugby and soccer.

PMID- 17557057
TI  - Evolution of physiological and haematological parameters with training load in
      elite male road cyclists: a longitudinal study.
AB  - AIM: The aim of this study was to describe and evaluate physiological parameters
      as a control tool for the monitoring of training in a group of elite cyclists
      during one season of training. METHODS: The study is divided into two periods
      (winter or ''volume'' mesocycle and spring or ''intensity'' mesocycle) between
      the tests that they carried out in the laboratory, consisting of a ramp test to
      exhaustion (work load increases 25 W X min(-1)) and a maximal lactate steady
      state (MLSS) test on a cycle ergometer. Macronutrients and hematological
      variables were recorded during the test periods as were the volume and the
      intensity of training sessions during the whole period of the study. RESULTS: The
      physiological data were similar to those previously reported for professional
      cyclists (approximately 450 Watts, approximately 78 mL x kg(-1) x min(-1)) and
      the values for the MLSS also agree with previous studies (approximately 250
      Watts). Subjects improved the first ventilatory threshold (VT(1)) (approximately
      52% to approximately 60% VO(2max)) and the second ventilatory threshold (VT(2))
      (approximately 82% to approximately 87% VO(2max)) after the first period of
      training even though its low intensity focused on the performance of VT(1) (77%
      training in ''zone 1'', under VT(1)). The MLSS improved after the first period
      (approximately 225 to approximately 250 Watts) and remained high in the second
      (approximately 255 Watts). High levels of creatine kinase (approximately 230 U x
      L(-1)) and urea (37 mg x L(-1)) were found, also a decrease in hemoglobin values
      (approximately 15.4 to approximately 14.7g x dL(-1)). CONCLUSION: The high level
      reached by the subjects after the first period of training suggests that two
      effort tests could be enough to plan training. On the other hand, the decrease in
      some red blood cell and nutrition parameters suggests that there should be
      greater control over them during the season.

PMID- 17557058
TI  - Anthropometric profiles of elite Asian female handball players.
AB  - AIM: Handball has increased in status as a sport since its introduction in 1972
      into the Summer Olympic Games. Whereas anthropometric profiles of female athletes
      have been reported for certain sports, data for elite handball players are
      limited. The current study was based on anthropometric measurements of 60 female
      Asian handball players competing in the continental championship, the aim being
      to identify any differences between countries and between playing positions.
      METHODS: The setting was the 12(th) Asian Games in Hiroshima, Japan.
      Anthropometric data were obtained from 60 players including teams from China,
      Japan, Kazakhstan and South Korea. Measurements included height, mass, skinfold
      thicknesses: from these measures percent body fat and muscle mass were estimated.
      Profiles were compared between 4 nations and 4 positional roles by means of
      ANOVA. RESULTS: Overall, mean (SD) values were 1.708 (0.068) m, 64.6 (7.7) kg,
      20.8% (4.4%), 39.6% (5.2%) for stature, mass, percent body fat and percent muscle
      mass, respectively. There were small differences between players from different
      countries but no significant (P>0.05) influence of playing position. Players from
      Japan were shortest, lightest and lowest in adiposity. The Chinese players were
      tallest and had the greatest muscle mass. CONCLUSION: These female international
      handball players differed in some respects in anthropometric characteristics
      according to their country of origin. The Asian players were found to be
      relatively homogeneous across the different positions.

PMID- 17557059
TI  - Injury survey in competitive sub-elite rhythmic gymnasts: results from a
      prospective controlled study.
AB  - AIM: The aim of this study was to determine the frequency, anatomical site and
      types of injury incurred in rhythmic gymnastics. METHODS: An 8-month prospective
      and controlled injury survey was planned, including 70 club-level competitive
      rhythmic gymnasts, aged 13-19 years. Information on injury events was recorded
      weekly in an injury record booklet for any event occurring over that week.
      Height, weight, anthropometric measurements and time spent in physical activity
      were recorded at baseline. Data from 72 age-matched non-athletic females served
      as controls. RESULTS: Forty-nine significant injuries were reported by gymnasts
      and 34 by controls (70% vs 47%, P<0.005, odds ratio 2.28); gymnasts sustained a
      rate of 1.08 injuries per 1 000 h of training. The most prevalent anatomical
      sites sustaining injury were the ankle and the foot (38.9%), followed by back
      (22.2%). Strains and sprains were frequently reported both in gymnasts and in
      controls. Gymnasts missed an average of 4.1 days of physical activity as compared
      to 18.9 days for the control females. Alternatively, modification of training
      sessions occurred more frequently for the gymnast group (32 vs 7 cases for
      controls). The total school days missed were lower for the injured gymnasts than
      for the injured controls (27 vs 64 days). CONCLUSION: Competitive, club-level
      rhythmic gymnastics show a higher prevalence of injuries than non-athletic
      controls, but considering the high number of hours spent in training sessions, it
      derives that rhythmic gymnasts is a sport discipline at relatively low risk of
      severe injuries. These are mainly limited to back and lower limbs, are generally
      not severe and do not significantly hinder the preparation for the competitions.

PMID- 17557060
TI  - Position statement. Asthma diagnosis and treatment.

PMID- 17557061
TI  - Influence of changes in visual acuity under various visual field conditions on
      the spectral characteristics of center of pressure sway.
AB  - AIM: This study aimed to examine the influence of visual information (visual
      acuity and visual field conditions) on the center of pressure (COP) sway
      spectrum. METHODS: The subjects were 17 healthy young adults (7 males and 10
      females), whose naked eye binocular visual acuity was under 0.2 (mean naked eye
      visual acuity: 0.1+/-0.1; mean corrected vision: 1.3+/-0.3). They participated in
      COP measurements under 2 kinds of visual acuity conditions (naked eye and vision
      correction conditions) and 3 visual field conditions (no vision: no visual
      information; central vision: only central visual field information; and full
      vision: full visual information). Spectral characteristics of COP sway of
      anterior/posterior (Y) and medial/lateral (X) directions were assessed using mean
      power frequency and frequency of maximal power (FMP). RESULTS: The Friedman test
      and Scheffe's pairwise comparison test showed that the FMP of posterior-anterior
      COP sway was higher in no vision and central vision than in the full vision
      condition in the vision correction condition. In the naked eye condition, there
      was no significant difference in any parameter between visual field conditions.
      CONCLUSION: In summary, although people with low visual acuity are little
      affected by changes of visual fields with naked eyes, with temporal vision
      correction they show differences in X and Y sway spectrum characteristics between
      visual field conditions. During vision correction, the wider their visual fields,
      the more low frequency sway they have. Even a temporal improvement of visual
      acuity may contribute to stability in an upright standing posture.

PMID- 17557062
TI  - Habitual physical activity levels in childhood and adolescence assessed with
      accelerometry.
AB  - AIM: The purposes of this study were: 1) to evaluate age and gender differences
      in physical activity (PA) of children and adolescents; 2) to find out if children
      and adolescents fulfill the PA recommendations of 60 min x day(-1) of moderate
      (MPA) to vigorous PA (VPA). METHODS: PA was assessed in 265 female and 238 male
      subjects, ranging from 6 to 18 years of age, grouped in 4 age groups, with MTI
      ActiGraph model 7164, during 7 consecutive days. The MTI actigraph data was
      reduced to bouts (30-, 20-, 10-, and 5-min) and minutes spent in MPA, VPA, and
      very VPA (VVPA). RESULTS: The oldest boys and girls revealed a lower number of PA
      bouts than the younger ones. Significant gender differences were found in daily
      VPA, F(1, 492)=37.67, P<0.001; and VVPA F(1, 494)=24.11, P<0.001. Boys were more
      active than girls. Significant age group differences were also found in MPA, F(3,
      494)=87.4, P<0.001; VPA, F(3, 492)=78.15, P<0.001; and VVPA, F(3, 454)=54.89,
      P<0.001. In both genders MPA, VPA and VVPA decreased with age. Till the age of
      14, children had means between 79.6+/-30.6 and 144.1+/-76.9 min*day(-1) of PA.
      After this age, there was a decrease to 44.1+/-19.9 min*day(-1) in girls and to
      56.3+/-31.9 min*day(-1) in boys. CONCLUSION: Boys had more minutes a day of VPA
      and VVPA than girls. PA decreased with age. The subjects of this study, aged 6 to
      15, fulfilled the recommendations of 60 min x day(-1) of MPA to VPA.

PMID- 17557063
TI  - Effect of exercise on levels of cyclo-oxygenase mediators in exhaled breath
      condensate in elite athletes.
AB  - AIM: Physical exercise requires adaptation from the airways, which includes
      bronchodilation. Prostaglandins are involved in airway regulation and their
      plasma level changes during exercise. The purpose of this study was to
      investigate the effect of symptom-limited exercise on the levels of prostaglandin
      E(2) (PGE2) and thromboxane B2 (TXB2) in the airways of elite sportsmen. METHODS:
      Thirty healthy judo competitors, 15 women and 13 men, aged between 16 and 30
      years, participated in this study. Subjects completed a standardized maximal
      treadmill exercise test. Exhaled breath condensate was collected for non-invasive
      sampling of the airway lining fluid before and immediately after the exercise.
      PGE2 and TXB2 levels were determined by commercially available radioimmunoassay.
      Data are given as median (range). RESULTS: Baseline levels of PGE2 and TXB2 were
      not different between male and female subjects. Exercise caused a significant
      increase both in PGE2 and TXB2 concentrations in male subjects (from 180 [100
      350] to 240 [115-720] pg/mL, P<0.01 and from 24 [0-80] to 37 [0-110] pg/mL,
      P<0.05, respectively), but not in female subjects. CONCLUSION: Our data indicate
      that physical exercise modulates the airway level of PGE2 and TXB2 in healthy
      subjects. These changes may play an important role in the airway adaptation to
      exercise.

PMID- 17557064
TI  - The relationship between sources of motivation and level of practice in young
      Portuguese swimmers.
AB  - AIM: The aim of this study was to examine the relationship between participation
      motives and level of practice in young Portuguese swimmers and to investigate
      whether swimmers with a different expertise differ in their reasons for
      participation involvement. METHODS: A total of 155 subjects (68 male and 87
      female), aged 7 to 18 years, responded to the Portuguese versions of the
      Participation Motivation Inventory. The subjects were divided into those
      participating in learn-to swim programs (n=40), advanced programs (n=49) or
      competition (n=56). RESULTS: A significant multivariate effect was obtained for
      level of practice, with children involved in learn-to swim programs rating
      fitness, competition, general affiliation, technical skills and fun significantly
      lower in importance than the other two groups. A 2 (subject gender) x3 (practice
      level) MANCOVA, with age at dropout, revealed that the effect of the covariate
      itself was not significant, but a main effect was found for gender, differing
      boys and girls only in the emotion factor. A significant interaction was also
      detected between gender and participation level, with a higher importance given
      to general affiliation by girls in comparison to boys in the advanced programs
      and competition categories. CONCLUSION: Our results in a sample of Portuguese
      swimmers indicate the existence of multiple motives for participation and
      significant differences in motivational factors in relation to the practice
      level.

PMID- 17557065
TI  - ACE I/D gene polymorphism and aerobic endurance development in response to
      training in a non-elite female cohort.
AB  - AIM: The aim of this study was to investigate the association between ACE gene
      polymorphism and short- and medium-duration aerobic endurance performance
      improvements in response to the same training regimen in a non-elite female
      cohort. METHODS: Fifty-five female non-elite Caucasian Turkish athletes trained
      to enhance running speeds corresponding to 70% and 90% of heart rate reserve (V
      HRR70 and V-HRR90 respectively) 30 min running speed performance (V-30min) 3
      times per week, for 6 weeks. ACE gene polymorphisms studied by PCR analysis.
      RESULTS: The distribution of genotypes in the whole cohort was 21.8%, 41.8%,
      36.4% for II (n=12), ID (n=23) and DD (n=20), respectively. Subjects with ACE II
      genotype had significantly higher improvements in V-30min and V-HRR70 than the
      ACE DD group (P<0.05). However, in HRR90 ACE DD genotype had a better performance
      enhancement in running speed than others (P<0.05). Endurance improvements in the
      V-HRR70 and in the V-30min showed a linear trend as II>ID>DD (P<0.05 and P<0.01,
      respectively) while a linear trend as DD>ID>II (P<0.01) observed in V-HRR90.
      CONCLUSION: ACE II genotype may related with better improvements in medium
      duration aerobic endurance performance whilst ACE DD genotype seems to be more
      advantageous in performance enhancement in shorter duration and higher intensity
      endurance activities.

PMID- 17557066
TI  - Endorphin responses to stress induced by competitive swimming event.
AB  - AIM: The aim of the present study was to investigate the changes in endorphins
      (END) induced by swimming competitive practice. METHODS: Twenty-three males, (13
      trained swimmers [experimental group] and 10 sedentary and healthy students [age
      matched comparison group]) took part in this investigation. The swimmers were
      assessed at 3 points: basal conditions, pre- and postswimming competition (100 m
      freestyle), whereas subjects from the control group only undertook the basal
      trial. The variables analysed were anxiety level, plasma END and lactate
      concentrations. RESULTS: No statistical differences were observed in END basal
      levels between groups. An evident END response to precompetition psychological
      stress was observed in the experimental group, since the plasma END concentration
      rose from 36.3+/-2.9 pg/mL (basal conditions) to 51.8+/-3.2 pg/mL (P=0.05). The
      END response to the competitive effort produced a remarkable increase in its
      plasma concentration (128.6+/-18.1 pg/mL), showed statistical differences from
      precompetition (P=or<0.01) and from basal conditions (P=or<0.001). A significant
      rise in plasma lactate levels just at the end of the effort was found, although
      it did not correlate with END levels in the same situation. CONCLUSION: Swimming
      competition (short-term maximal type of effort) induces a psychological and
      physiological stress, which stimulates the secretion of END. END are secreted to
      counter the negative effects of competitive stress, although more research is
      needed to accurate the relationship between END and anxiety levels during
      exercise.

PMID- 17557067
TI  - Changes of cytosol glucocorticoid receptor and renal Na(+)-K(+)-ATPase activity
      after swimming training in rat.
AB  - AIM: The aim of this study was to determine whether the down-regulation of
      glucocorticoid receptor (GR) by physical changes in plasma glucocorticoid
      hormones (GCs) is accompanied by changes in the responsiveness of target cells to
      GCs in rats. METHODS: Normal male Sprague-Dawley rats were left to swim for 60
      min. At 15 min and at 3, 12, 24 h after swimming training, groups of rats were
      sacrificed. RESULTS: The results show that exposure of rats to a 60-min swimming
      stress provokes corticosterone secretion, which results in a rapid depletion of
      GR from renal cytosol and the subsequent induction of the renal Na(+)-K(+)
      ATPase. By employing RU38486 and Trilostane before swimming training, both the
      effects of GCs on regulating GR binding activity and related changes in GR
      binding capacity to Na(+)-K(+)-ATPase activity are also investigated. RU38486 was
      shown to reduce GR by about 80% and the inducing effort of GCs on Na(+)-K(+)
      ATPase was prevented by pretreatment of RU38486 and Trilostane. CONCLUSION: These
      data suggest that physiological fluctuations in endogenous hormone secretion are
      sufficient to result not only in substantial cytosol GR down-regulation, but in a
      coordinate physiological response.

PMID- 17557068
TI  - The distribution of I/D polymorphism in the ACE gene among Korean male elite
      athletes.
AB  - AIM: The aim of this study was to examine the distribution of insertion/deletion
      (I/D) polymorphism in the ACE gene among Korean male elite athletes. METHODS:
      Participants of the study were 139 Korean male elite athletes (15 basketball, 41
      soccer, 31 baseball, 12 gymnastics, 7 volleyball, 8 long-distance running, 8
      judo, and 17 ice hockey players). The control group consisted of 163 non
      athletes. Polymerase chain reaction method was used to investigate I/D
      polymorphism of the ACE gene. Collected data were analyzed by SPSS 11.0 program.
      RESULTS: The distribution of genotype and allele frequencies did not indicate the
      differences between the athletes and controls (P>0.05). However, the excess of II
      genotype and I allele was shown in long distance runners, although it was not
      statistically significant. CONCLUSION: It may be necessary to perform further
      studies using a homogeneous cohort of subjects from single sporting discipline,
      because the probable role of I allele in athletic performance has been hard to be
      detected by heterogeneous groups of diverse sporting disciplines.

PMID- 17557069
TI  - Menstrual cycle stage and oral contraceptive effects on anterior tibial
      displacement in collegiate female athletes.
AB  - AIM: The aim of this study was to establish if differences in anterior tibial
      displacement exists in collegiate female student-athletes at different stages of
      the menstrual cycle. METHODS:  DESIGN AND SETTING: a 2 x 3 factorial design with
      repeated measures on the second factor guided this study. The first independent
      variable was group with 2 levels (control and oral contraceptive) and the second
      independent variable was menstrual cycle phase with 3 levels (follicular,
      ovulation, luteal). The single dependent variable was anterior tibial
      displacement. All data were collected in a research laboratory. SUBJECTS: 53
      female student athletes (control: n=28; oral contraceptive: n=25) with no
      previous history of knee injury or anomalies with a normal 28-30 day menstrual
      cycle participated. MEASUREMENTS: anterior tibial displacement (mm) measurements
      were taken on days 1 (follicular phase), 13 (ovulation phase), and 23 (luteal
      phase) of each subject's menstrual cycle using a KT1000 knee arthrometer.
      RESULTS: For the entire group, statistically significant increases in anterior
      tibial laxity were found (F=4.49; df=52.1; P<0.05) between the follicular cycle
      (0+/-SD =5.14 mm) and ovulation cycle (0+/-SD=5.81 mm); and follicular cycle (0+/
      SD=5.14 mm) and luteal cycle (0+/-SD=5.79 mm). A separate analysis of the non
      birth control group revealed no significant difference in anterior tibial laxity
      throughout the stages of the menstrual cycle. CONCLUSION: The results of this
      study suggest that: 1) the menstrual cycle does have an influence on laxity of
      the anterior displacement of the knee; 2) significant increases in anterior
      displacement are shown during the ovulation and luteal phases of the menstrual
      cycle; and 3) birth control subjects tend to have increased laxity when compared
      to those subjects who are not on hormone therapy.

PMID- 17557070
TI  - Decline in breast cancer incidence--United States, 1999-2003.
AB  - Breast cancer is the most commonly diagnosed cancer among females in the United
      States. The 2006 Annual Report to the Nation on the Status of Cancer described a
      stabilization in female breast cancer incidence rates during 2001-2003, ending
      increases that began in the 1980s, and a decline in the number of breast cancer
      cases diagnosed in 2003. In addition, researchers who used 1990-2003 data from
      the National Cancer Institute's (NCI's) Surveillance, Epidemiology, and End
      Results (SEER) program, representing approximately 14% of the U.S. population,
      reported a 7% decrease in invasive breast cancer rates from 2002 to 2003. To
      further assess breast cancer annual incidence rates during 1999-2003, CDC
      analyzed data collected by CDC's National Program of Cancer Registries (NPCR) and
      the NCI SEER program. These combined data account for approximately 86% of the
      U.S. population. The results of this analysis indicated that age-adjusted
      incidence rates for invasive breast cancer decreased each year during 1999-2003,
      with the greatest decrease (6.1%) occurring from 2002 to 2003; women aged > or =
      50 years experienced a significant decrease during this period. Rates of in situ
      (i.e., noninvasive) breast cancer increased each year during 1999-2002 and then
      decreased from 2002 to 2003; women aged 50-79 years experienced a significant
      decrease during this period. Future studies should focus on determining potential
      causes for these decreases.

PMID- 17557071
TI  - Hazardous substances released during rail transit--18 states, 2002-2007.
AB  - In January 2007, two separate railroad incidents involving the unintentional
      release of hazardous substances occurred on consecutive days in Irvine and
      Brooks, two Kentucky communities approximately 125 miles apart. Although the
      incidents were not causally related, they both resulted in public health
      consequences (e.g., increased hospital visits, evacuations, and shelter-in-place
      orders (Kentucky Department for Public Health, unpublished data, 2007).
      Subsequently, the Agency for Toxic Substances and Disease Registry (ATSDR)
      reviewed data from the Hazardous Substances Emergency Events Surveillance (HSEES)
      system to update a previous analysis involving rail events. The HSEES system is
      used to collect and analyze data regarding the public health consequences
      associated with hazardous-substance release events, including those that occur
      during transportation. This report describes the two 2007 events in Kentucky (a
      non-HSEES state) and two other illustrative events in Minnesota in 2006 and in
      Utah in 2005, for which HSEES data were collected. In addition, this report
      summarizes all rail events reported to HSEES from 17 state health departments
      during 2002-2006.

PMID- 17557072
TI  - West Nile virus activity--United States, 2006.
AB  - West Nile virus (WNV) is the leading cause of arboviral encephalitis in the
      United States. Originally discovered in Africa in 1937, WNV was first detected in
      the western hemisphere in 1999 in New York City. Since then, WNV has caused
      seasonal epidemics of febrile illness and severe neurologic disease in the United
      States. This report summarizes provisional WNV surveillance data for 2006
      reported to CDC as of April 3, 2007. During 2006, WNV transmission to humans or
      animals expanded into 52 counties that had not previously reported transmission
      and recurred in 1,350 counties where transmission had been reported in previous
      years. In addition, 1,491 cases of WNV neuroinvasive disease (WNND) were reported
      in the United States during this period, amounting to a 14% increase from 2005
      and the largest number reported since 2003. On the basis of extrapolations from
      past serosurveys, an estimated 41,750 cases of non-neuroinvasive WNV disease
      occurred in 2006; of these cases, 2,770 were reported. These findings highlight
      the need for ongoing surveillance, mosquito control, promotion of personal
      protection from mosquito bites, and research into additional prevention
      strategies.

PMID- 17557073
TI  - Assisted reproductive technology surveillance - United States, 2004.
AB  - PROBLEM/CONDITION: In 1996, CDC initiated data collection regarding assisted
      reproductive technology (ART) procedures performed in the United States, as
      mandated by the Fertility Clinic Success Rate and Certification Act of 1992
      (FCSRCA) (Public Law 102-493 [October 24, 1992]). ART includes fertility
      treatments in which both eggs and sperm are handled in the laboratory (i.e., in
      vitro fertilization and related procedures). Patients who undergo ART procedures
      are more likely to deliver multiple-birth infants than women who conceive
      naturally. Multiple births are associated with increased risk for mothers and
      infants (e.g., pregnancy complications, premature delivery, low-birthweight
      infants, and long-term disability among infants). REPORTING PERIOD COVERED: 2004.
      DESCRIPTION OF SYSTEM: In 2004, CDC contracted with a statistical survey research
      organization, Westat, Inc., to obtain data from ART medical centers in the United
      States. Westat, Inc., maintains CDC's web-based data collection system called the
      National ART Surveillance System. RESULTS: In 2004, a total of 127,977 ART
      procedures were reported to CDC. These procedures resulted in 36,760 live-birth
      deliveries and 49,458 infants. Nationwide, 74% of ART procedures used freshly
      fertilized embryos from the patient's eggs, 15% used thawed embryos from the
      patient's eggs, 8% used freshly fertilized embryos from donor eggs, and 4% used
      thawed embryos from donor eggs. Overall, 42% of ART transfer procedures resulted
      in a pregnancy, and 34% resulted in a live-birth delivery (delivery of one or
      more live-born infants). The highest live-birth rates were observed among ART
      procedures that used freshly fertilized embryos from donor eggs (51%). The
      highest numbers of ART procedures were performed among residents of California
      (17,303), New York (11,123), Illinois (9,306), Massachusetts (8,906), and New
      Jersey (8,513). These five states also reported the highest number of infants
      conceived through ART. Of 49,458 infants born through ART, 50% were born in
      multiple-birth deliveries. The multiple-birth risk was highest for women who
      underwent ART transfer procedures that used freshly fertilized embryos from
      either donor eggs (40%) or their own eggs (33%). Approximately 1% of U.S. infants
      born in 2004 were conceived through ART. Those infants accounted for 18% of
      multiple births nationwide. Approximately 9% of ART singletons, 56% of ART twins,
      and 95% of ART triplets or higher-order multiples were low birthweight. The
      percentages of ART infants born preterm were 15% among singletons, 64% among
      twins, and 98% among triplets or higher-order multiples. INTERPRETATION: Whether
      an ART procedure resulted in a pregnancy and live-birth delivery varied according
      to different patient and treatment factors. ART poses a major risk for multiple
      births. This risk varied according to the patient's age, the type of ART
      procedure performed, the number of embryos transferred, the day of embryo
      transfer (day 3 or day 5), and embryo availability. PUBLIC HEALTH ACTIONS: ART
      related multiple births represent a sizable proportion of all multiple births
      nationwide and in selected states. To minimize the adverse maternal and child
      health effects that are associated with multiple pregnancies, ongoing efforts to
      limit the number of embryos transferred in each ART procedure should be continued
      and strengthened. Adverse maternal and infant outcomes (e.g., low birthweight and
      preterm delivery) associated with ART treatment choices should be explained fully
      when counseling patients who are considering ART.

PMID- 17557074
TI  - Malaria surveillance - United States, 2005.
AB  - PROBLEM/CONDITION: Malaria in humans is caused by any of four species of
      intraerythrocytic protozoa of the genus Plasmodium (i.e., P. falciparum, P.
      vivax, P. ovale, or P. malariae). These parasites are transmitted by the bite of
      an infective female Anopheles sp. mosquito. The majority of malaria infections in
      the United States occur among persons who have traveled to or from areas with
      ongoing malaria transmission. In the United States, cases can occur through
      exposure to infected blood products, congenital transmission, or local
      mosquitoborne transmission. Malaria surveillance is conducted to identify
      episodes of local transmission and to guide prevention recommendations for
      travelers. PERIOD COVERED: This report summarizes cases in persons with onset of
      illness in 2005 and summarizes trends during previous years. DESCRIPTION OF
      SYSTEM: Malaria cases confirmed by blood film or polymerase chain reaction (PCR)
      are mandated to be reported to local and state health departments by health-care
      providers or laboratory staff. Case investigations are conducted by local and
      state health departments, and reports are transmitted to CDC through the National
      Malaria Surveillance System (NMSS). Data from NMSS serve as the basis for this
      report. RESULTS: CDC received reports of 1,528 cases of malaria, including seven
      fatal cases, with an onset of symptoms in 2005 among persons in the United States
      or one of its territories. This number represents an increase of 15.4% from the
      1,324 cases reported for 2004. P. falciparum, P. vivax, P. malariae, and P. ovale
      were identified in 48.6%, 22.1%, 3.5%, and 2.5% of cases, respectively. Twelve
      patients (0.8% of total) were infected by two or more species. The infecting
      species was unreported or undetermined in 22.6% of cases. Compared with 2004, the
      largest increases in cases came from the Americas (23.1%; n = 213) and Asia and
      the Middle East (18.6%; n = 204). On the basis of estimated volume of travel, the
      highest estimated case rates of malaria among travelers occurred among those
      returning from West Africa. Of 870 U.S. civilians who acquired malaria abroad,
      only 160 (18.4%) reported that they had followed a chemoprophylactic drug regimen
      recommended by CDC for the area to which they had traveled. Two patients became
      infected in the United States, both attributed to congenital transmission; both
      were infected with P. vivax. Seven deaths were attributed to malaria, all caused
      by infection with P. falciparum. INTERPRETATION: The 15.4% increase in malaria
      cases in 2005, compared with 2004, resulted primarily from increases in the
      number of cases reported from Asia and the Middle East and from the Americas.
      This increase might in part reflect more complete reporting and in part increased
      travel to malarious areas. No change was noted in proportions of cases from other
      areas of the world, or in species responsible for the infection. In the majority
      of reported cases, U.S. civilians who acquired infection abroad had not adhered
      to a chemoprophylaxis regimen that was appropriate for the country in which they
      acquired malaria. U.S. civilians who traveled to West Africa had the highest
      estimated relative case rate. PUBLIC HEALTH ACTIONS: Additional investigations
      were conducted for the seven fatal cases and two infections acquired in the
      United States. Persons traveling to a malarious area should take one of the
      recommended chemoprophylaxis regimens appropriate for the region of travel and
      use personal protection measures to prevent mosquito bites. Any person who has
      been to a malarious area and who subsequently has a fever or influenza-like
      symptoms should seek medical care immediately and report their travel history to
      the clinician; investigation should include at least one blood-film test for
      malaria. Malaria infections can be fatal if not diagnosed and treated promptly.
      Recommendations concerning malaria prevention can be obtained from CDC at
      http://www.cdc.gov/travel or by calling the Malaria Hotline (telephone 770-488
      7788). Recommendations for malaria treatment can be obtained at
      http://www.cdc.gov/malaria/diagnosis_treatment/treatment.htm or by calling the
      Malaria Hotline.

PMID- 17557075
TI  - Constitutive activation of a plasma membrane H(+)-ATPase prevents abscisic acid
      mediated stomatal closure.
AB  - Light activates proton (H(+))-ATPases in guard cells, to drive hyperpolarization
      of the plasma membrane to initiate stomatal opening, allowing diffusion of
      ambient CO(2) to photosynthetic tissues. Light to darkness transition, high CO(2)
      levels and the stress hormone abscisic acid (ABA) promote stomatal closing. The
      overall H(+)-ATPase activity is diminished by ABA treatments, but the
      significance of this phenomenon in relationship to stomatal closure is still
      debated. We report two dominant mutations in the OPEN STOMATA2 (OST2) locus of
      Arabidopsis that completely abolish stomatal response to ABA, but importantly, to
      a much lesser extent the responses to CO(2) and darkness. The OST2 gene encodes
      the major plasma membrane H(+)-ATPase AHA1, and both mutations cause constitutive
      activity of this pump, leading to necrotic lesions. H(+)-ATPases have been
      traditionally assumed to be general endpoints of all signaling pathways affecting
      membrane polarization and transport. Our results provide evidence that AHA1 is a
      distinct component of an ABA-directed signaling pathway, and that dynamic
      downregulation of this pump during drought is an essential step in membrane
      depolarization to initiate stomatal closure.

PMID- 17557076
TI  - Human CIA30 is involved in the early assembly of mitochondrial complex I and
      mutations in its gene cause disease.
AB  - In humans, complex I of the respiratory chain is composed of seven mitochondrial
      DNA (mtDNA)-encoded and 38 nuclear-encoded subunits that assemble together in a
      process that is poorly defined. To date, only two complex I assembly factors have
      been identified and how each functions is not clear. Here, we show that the human
      complex I assembly factor CIA30 (complex I intermediate associated protein)
      associates with newly translated mtDNA-encoded complex I subunits at early stages
      in their assembly before dissociating at a later stage. Using antibodies we
      identified a CIA30-deficient patient who presented with cardioencephalomyopathy
      and reduced levels and activity of complex I. Genetic analysis revealed the
      patient had mutations in both alleles of the NDUFAF1 gene that encodes CIA30.
      Complex I assembly in patient cells was defective at early stages with subunits
      being degraded. Complementing the deficiency in patient fibroblasts with normal
      CIA30 using a novel lentiviral system restored steady-state complex I levels. Our
      results indicate that CIA30 is a crucial component in the early assembly of
      complex I and mutations in its gene can cause mitochondrial disease.

PMID- 17557077
TI  - The two chromosomes of Vibrio cholerae are initiated at different time points in
      the cell cycle.
AB  - The bacterium Vibrio cholerae, the cause of the diarrhoeal disease cholera, has
      its genome divided between two chromosomes, a feature uncommon for bacteria. The
      two chromosomes are of different sizes and different initiator molecules control
      their replication independently. Using novel methods for analysing flow cytometry
      data and marker frequency analysis, we show that the small chromosome II is
      replicated late in the C period of the cell cycle, where most of chromosome I has
      been replicated. Owing to the delay in initiation of chromosome II, the two
      chromosomes terminate replication at approximately the same time and the average
      number of replication origins per cell is higher for chromosome I than for
      chromosome II. Analysis of cell-cycle parameters shows that chromosome
      replication and segregation is exceptionally fast in V. cholerae. The divided
      genome and delayed replication of chromosome II may reduce the metabolic burden
      and complexity of chromosome replication by postponing DNA synthesis to the last
      part of the cell cycle and reducing the need for overlapping replication cycles
      during rapid proliferation.

PMID- 17557078
TI  - Selective redox regulation of cytokine receptor signaling by extracellular
      thioredoxin-1.
AB  - The thiol-disulfide oxidoreductase thioredoxin-1 (Trx1) is known to be secreted
      by leukocytes and to exhibit cytokine-like properties. Extracellular effects of
      Trx1 require a functional active site, suggesting a redox-based mechanism of
      action. However, specific cell surface proteins and pathways coupling
      extracellular Trx1 redox activity to cellular responses have not been identified
      so far. Using a mechanism-based kinetic trapping technique to identify disulfide
      exchange interactions on the intact surface of living lymphocytes, we found that
      Trx1 catalytically interacts with a single principal target protein. This target
      protein was identified as the tumor necrosis factor receptor superfamily member 8
      (TNFRSF8/CD30). We demonstrate that the redox interaction is highly specific for
      both Trx1 and CD30 and that the redox state of CD30 determines its ability to
      engage the cognate ligand and transduce signals. Furthermore, we confirm that
      Trx1 affects CD30-dependent changes in lymphocyte effector function. Thus, we
      conclude that receptor-ligand signaling interactions can be selectively regulated
      by an extracellular redox catalyst.

PMID- 17557079
TI  - Drosophila Omi, a mitochondrial-localized IAP antagonist and proapoptotic serine
      protease.
AB  - Although essential in mammals, in flies the importance of mitochondrial outer
      membrane permeabilization for apoptosis remains highly controversial. Herein, we
      demonstrate that Drosophila Omi (dOmi), a fly homologue of the serine protease
      Omi/HtrA2, is a developmentally regulated mitochondrial intermembrane space
      protein that undergoes processive cleavage, in situ, to generate two distinct
      inhibitor of apoptosis (IAP) binding motifs. Depending upon the proapoptotic
      stimulus, mature dOmi is then differentially released into the cytosol, where it
      binds selectively to the baculovirus IAP repeat 2 (BIR2) domain in Drosophila
      IAP1 (DIAP1) and displaces the initiator caspase DRONC. This interaction alone,
      however, is insufficient to promote apoptosis, as dOmi fails to displace the
      effector caspase DrICE from the BIR1 domain in DIAP1. Rather, dOmi alleviates
      DIAP1 inhibition of all caspases by proteolytically degrading DIAP1 and induces
      apoptosis both in cultured cells and in the developing fly eye. In summary, we
      demonstrate for the first time in flies that mitochondrial permeabilization not
      only occurs during apoptosis but also results in the release of a bona fide
      proapoptotic protein.

PMID- 17557081
TI  - US biodefense--shocking and awful.

PMID- 17557080
TI  - HIV-1 DNA Flap formation promotes uncoating of the pre-integration complex at the
      nuclear pore.
AB  - The HIV-1 central DNA Flap acts as a cis-acting determinant of HIV-1 genome
      nuclear import. Indeed, DNA-Flap re-insertion within lentiviral-derived gene
      transfer vectors strongly stimulates gene transfer efficiencies. In this study,
      we sought to understand the mechanisms by which the central DNA Flap mediates HIV
      1 nuclear import. Here, we show that reverse transcription (RT degrees) occurs
      within an intact capsid (CA) shell, independently of the routing process towards
      the nuclear membrane, and that uncoating is not an immediate post-fusion event,
      but rather occurs at the nuclear pore upon RT degrees completion. We provide the
      first observation with ultrastructural resolution of intact intracellular HIV-1
      CA shells by scanning electron microscopy. In the absence of central DNA Flap
      formation, uncoating is impaired and linear DNA remains trapped within an
      integral CA shell precluding translocation through the nuclear pore. These data
      show that DNA Flap formation, the very last event of HIV-1 RT degrees, acts as a
      viral promoting element for the uncoating of HIV-1 at the nuclear pore.

PMID- 17557082
TI  - Superscience me!

PMID- 17557083
TI  - Australia tackles bird flu using RNAi.

PMID- 17557084
TI  - FDA likely to further restrict erythropoietin use for cancer patients.

PMID- 17557085
TI  - Licensing deals morph to acquisitions in seller's market.

PMID- 17557086
TI  - User-fee bill passes US Senate, but legislative hurdles remain.

PMID- 17557088
TI  - Alfred E. Mann.

PMID- 17557089
TI  - Tech transfer fails to translate into startups.

PMID- 17557090
TI  - Biotech at the beauty counter.

PMID- 17557091
TI  - What we know and don't know about Golden Rice.

PMID- 17557092
TI  - Trends in GM crop, food and feed safety literature.

PMID- 17557094
TI  - DNA synthesis and biological security.

PMID- 17557095
TI  - MicroRNA gets down to business.

PMID- 17557096
TI  - Time waits for no man: deciding when to file a patent application in Europe.

PMID- 17557097
TI  - Recent patent applications in DNA synthesis.

PMID- 17557098
TI  - Assisted suicide for retroviruses.

PMID- 17557099
TI  - A green light to expression in time and space.

PMID- 17557100
TI  - Membrane proteins up for grabs.

PMID- 17557102
TI  - Improving the success rate of proteome analysis by modeling protein-abundance
      distributions and experimental designs.
AB  - Truly comprehensive proteome analysis is highly desirable in systems biology and
      biomarker discovery efforts. But complete proteome characterization has been
      hindered by the dynamic range and detection sensitivity of experimental designs,
      which are not adequate to the very wide range of protein abundances. Experimental
      designs for comprehensive analytical efforts involve separation followed by mass
      spectrometry-based identification of digested proteins. Because results are
      generally reported as a collection of identifications with no information on the
      fraction of the proteome that was missed, they are difficult to evaluate and
      potentially misleading. Here we address this problem by taking a holistic view of
      the experimental design and using computer simulations to estimate the success
      rate for any given experiment. Our approach demonstrates that simple changes in
      typical experimental designs can enhance the success rate of proteome analysis by
      five- to tenfold.

PMID- 17557106
TI  - Managing change in biotech: mergers and acquisitions.

PMID- 17557108
TI  - Combination of the oncolytic adenovirus ICOVIR-5 with chemotherapy provides
      enhanced anti-glioma effect in vivo.
AB  - Novel therapies are clearly needed for gliomas, and the combination of oncolytic
      vectors with chemotherapy possesses a significant hope for the treatment of this
      malignancy. In addition, combination with chemotherapy allows for lower virus
      doses to achieve anticancer effect, thus resulting in lower undesirable
      toxicities due to viral proteins. In this work, we sought to determine whether
      combination of an oncolytic adenovirus ICOVIR-5, with RAD001 or temozolomide
      (TMZ) could result in enhanced anti-glioma effect in vivo. We assessed the in
      vitro cytotoxic effect and replication properties of ICOVIR-5 in combination with
      RAD001 or TMZ in U87 MG glioma cell line by MTT and TCID(50), respectively. Our
      data showed that in vitro treatment with RAD001 or TMZ not only interfered with
      adenovirus replication but, in addition, enhanced its oncolytic properties. To
      evaluate the in vivo anticancer effect, athymic mice bearing glioma xenografts (5
      x 10(5) U87 MG cells/animal) received a single intratumoral injection of ICOVIR-5
      (10(7) PFU/animal). RAD001 was given as a regimen of 5 mg/kg 5 days per week
      until the end of the experiment and TMZ was administered for 5 days at 7.5
      mg/kg/mice. Of significance, combination of ICOVIR-5 with RAD001 or TMZ showed a
      potent anti-glioma effect in vivo, resulting in a dramatic extension of the
      median animal survival and in 20-40% animals becoming free of disease beyond 90
      days.

PMID- 17557109
TI  - Intratumoral injection of IL-12 plasmid DNA--results of a phase I/IB clinical
      trial.
AB  - Effective eradication of established tumor and generation of a lasting systemic
      immune response are the goals of cancer immunotherapy. The objective of this
      phase IB study was to assess the safety and toxicity of treatment to metastatic
      tumor underlying the skin with the DNA encoding interleukin-12 (IL-12). This
      treatment strategy allowed the patient's own tumor to serve as a source of
      autologous antigen in the tumor microenvironment. We proposed that IL-12 protein
      produced by the transfected cells would result in the generation of both a local
      and systemic antitumor response. The tumor was treated with either three or six
      intratumoral injections of plasmid containing IL-12 DNA. This treatment strategy
      resulted in no significant local or systemic toxicity. The treatment did not
      result in an increase in serum IL-12 protein. The size of the treated lesion
      decreased significantly (greater than 30%) in five of the 12 patients. However,
      nontreated subcutaneous lesions or other disease did not decrease in size.

PMID- 17557110
TI  - Antitumor effects of non-replicative herpes simplex vectors expressing
      antiangiogenic proteins and thymidine kinase on Lewis lung carcinoma
      establishment and growth.
AB  - There is growing evidence that combinations of antiangiogenic proteins with other
      antineoplastic treatments such as chemo- or radiotherapy and suicide genes
      mediated tumor cytotoxicity lead to synergistic effects. In the present work, we
      tested the activity of two non-replicative herpes simplex virus (HSV)-1-based
      vectors, encoding human endostatin::angiostatin or endostatin::kringle5 fusion
      proteins in combination with HSV-1 thymidine kinase (TK) molecule, on endothelial
      cells (ECs) and Lewis lung carcinoma (LLC) cells. We observed a significant
      reduction of the in vitro growth, migration and tube formation by primary ECs
      upon direct infection with the two recombinant vectors or cultivation with
      conditioned media obtained from the vector-infected LLC cells. Moreover, direct
      cytotoxic effect of HSV-1 TK on both LLC and ECs was demonstrated. We then tested
      the vectors in vivo in two experimental settings, that is, LLC tumor growth or
      establishment, in C57BL/6 mice. The treatment of pre-established subcutaneous
      tumors with the recombinant vectors with ganciclovir (GCV) induced a significant
      reduction of tumor growth rate, while the in vitro infection of LLC cells with
      the antiangiogenic vectors before their implantation in mice flanks, either in
      presence or absence of GCV, completely abolished the tumor establishment.

PMID- 17557111
TI  - Molecular architecture of the human GINS complex.
AB  - Chromosomal DNA replication is strictly regulated through a sequence of steps
      that involve many macromolecular protein complexes. One of these is the GINS
      complex, which is required for initiation and elongation phases in eukaryotic DNA
      replication. The GINS complex consists of four paralogous subunits. At the G1/S
      transition, GINS is recruited to the origins of replication where it assembles
      with cell-division cycle protein (Cdc)45 and the minichromosome maintenance
      mutant (MCM)2-7 to form the Cdc45/Mcm2-7/GINS (CMG) complex, the presumed
      replicative helicase. We isolated the human GINS complex and have shown that it
      can bind to DNA. By using single-particle electron microscopy and three
      dimensional reconstruction, we obtained a medium-resolution volume of the human
      GINS complex, which shows a horseshoe shape. Analysis of the protein interactions
      using mass spectrometry and monoclonal antibody mapping shows the subunit
      organization within the GINS complex. The structure and DNA-binding data suggest
      how GINS could interact with DNA and also its possible role in the CMG helicase
      complex.

PMID- 17557112
TI  - The N terminus of the serpin, tengpin, functions to trap the metastable native
      state.
AB  - Serpins fold to a metastable native state and are susceptible to undergoing
      spontaneous conformational change to more stable conformers, such as the latent
      form. We investigated conformational change in tengpin, an unusual prokaryotic
      serpin from the extremophile Thermoanaerobacter tengcongensis. In addition to the
      serpin domain, tengpin contains a functionally uncharacterized 56-amino-acid
      amino-terminal region. Deletion of this domain creates a variant--tengpinDelta51-
      which folds past the native state and readily adopts the latent conformation.
      Analysis of crystal structures together with mutagenesis studies show that the N
      terminus of tengpin protects a hydrophobic patch in the serpin domain and
      functions to trap tengpin in its native metastable state. A 13-amino-acid peptide
      derived from the N terminus is able to mimick the role of the N terminus in
      stabilizing the native state of tengpinDelta51. Therefore, the function of the N
      terminus in tengpin resembles protein cofactors that prevent mammalian serpins
      from spontaneously adopting the latent conformation.

PMID- 17557113
TI  - Quorum sensing has an unexpected role in virulence in the model pathogen
      Citrobacter rodentium.
AB  - The bacterial mouse pathogen Citrobacter rodentium causes attaching and effacing
      (AE) lesions in the same manner as pathogenic Escherichia coli, and is an
      important model for this mode of pathogenesis. Quorum sensing (QS) involves
      chemical signalling by bacteria to regulate gene expression in response to cell
      density. E. coli has never been reported to have N-acylhomoserine lactone (AHL)
      QS, but it does utilize luxS-dependent signalling. We found production of AHL QS
      signalling molecules by an AE pathogen, C. rodentium. AHL QS is directed by the
      croIR locus and a croI mutant is affected in its surface attachment, although not
      in Type III secretion. AHL QS has an important role in virulence in the mouse as,
      unexpectedly, the QS mutant is hypervirulent; by contrast, we detected no impact
      of luxS inactivation. Further study of QS in Citrobacter should provide new
      insights into AE pathogenesis. As the croIR locus might have been horizontally
      acquired, AHL QS might exist in some strains of pathogenic E. coli.

PMID- 17557115
TI  - The Fas ligand intracellular domain is released by ADAM10 and SPPL2a cleavage in
      T-cells.
AB  - Fas ligand (FasL) is a type II transmembrane protein belonging to the tumor
      necrosis factor family. Its binding to the cognate Fas receptor triggers the
      apoptosis that plays a pivotal role in the maintenance of immune system
      homeostasis. The cell death-inducing property of FasL has been associated with
      its extracellular domain, which can be cleaved off by metalloprotease activity to
      produce soluble FasL. The fate of the remaining membrane-anchored N-terminal part
      of the FasL molecule has not been determined. Here we show that post
      translational processing of overexpressed and endogenous FasL in T-cells by the
      disintegrin and metalloprotease ADAM10 generates a 17-kDa N-terminal fragment,
      which lacks the receptor-binding extracellular domain. This FasL remnant is
      membrane anchored and further processed by SPPL2a, a member of the signal peptide
      peptidase-like family of intramembrane-cleaving proteases. SPPL2a cleavage
      liberates a smaller and highly unstable fragment mainly containing the
      intracellular FasL domain (FasL ICD). We show that this fragment translocates to
      the nucleus and is capable of inhibiting gene transcription. With ADAM10 and
      SPPL2a we have identified two proteases implicated in FasL processing and release
      of the FasL ICD, which has been shown to be important for retrograde FasL
      signaling.

PMID- 17557114
TI  - The role of LANP and ataxin 1 in E4F-mediated transcriptional repression.
AB  - The leucine-rich acidic nuclear protein (LANP) belongs to the INHAT family of
      corepressors that inhibits histone acetyltransferases. The mechanism by which
      LANP restricts its repression to specific genes is unknown. Here, we report that
      LANP forms a complex with transcriptional repressor E4F and modulates its
      activity. As LANP interacts with ataxin 1--a protein mutated in the
      neurodegenerative disease spinocerebellar ataxia type 1 (SCA1)--we tested whether
      ataxin 1 can alter the E4F-LANP interaction. We show that ataxin 1 relieves the
      transcriptional repression induced by the LANP-E4F complex by competing with E4F
      for LANP. These results provide the first functional link, to our knowledge,
      between LANP and ataxin 1, and indicate a potential mechanism for the
      transcriptional aberrations observed in SCA1.

PMID- 17557116
TI  - Toxicology and carcinogenesis studies of methyl isobutyl ketone (Cas No. 108-10
      1) in F344/N rats and B6C3F1 mice (inhalation studies).
AB  - Methyl isobutyl ketone is used as a denaturant for rubbing alcohol; as a solvent
      for paints, varnishes, nitrocellulose, lacquers, and protective coatings; in
      industrial extraction processes; in dry-cleaning preparations; and in the
      synthesis of methyl isobutyl carbinol. Methyl isobutyl ketone was nominated for
      study by the National Cancer Institute and the United States Environmental
      Protection Agency because of its widespread use, the high potential for worker
      exposure due to its many industrial applications, and its high production volume.
      Male and female F344/N rats and B6C3F1 mice were exposed to methyl isobutyl
      ketone (greater than 99% pure) by inhalation for 2 years. Genetic toxicology
      studies were conducted in Salmonella typhimurium. 2-YEAR STUDY IN RATS: Groups of
      50 males and 50 females were exposed to methyl isobutyl ketone at concentrations
      of 0, 450, 900, or 1,800 ppm by inhalation, 6 hours plus T(90) (12 minutes) per
      day, 5 days per week for 104 weeks. Survival of males exposed to 1,800 ppm was
      significantly less than that of the chamber controls. The mean body weights of
      the 900 and 1,800 ppm males were less than those of the chamber controls after
      weeks 97 and 89, respectively. In the standard evaluation of the kidney, there
      were slightly increased incidences of renal tubule adenoma and renal tubule
      adenoma or carcinoma (combined) in males exposed to 900 or 1,800 ppm, and renal
      tubule carcinoma in males exposed to 1,800 ppm. The incidences of renal tubule
      hyperplasia were also significantly increased in the 450 and 1,800 ppm males, and
      the severities were greater than in the chamber controls. Chronic nephropathy
      occurred in all males exposed to 1,800 ppm and in 70% to 88% of exposed females,
      and the severity was increased in 1,800 ppm males. The incidences of transitional
      epithelial hyperplasia of the renal pelvis in males exposed to 900 or 1,800 ppm
      and mineralization of the renal papilla in all groups of exposed males were
      significantly increased. In addition, two female rats exposed to 1,800 ppm had
      renal mesenchymal tumors. In the extended evaluation of the kidney, renal tubule
      adenomas and renal tubule hyperplasia occurred in all groups of exposed male
      rats. In the combined single and step section analysis, the incidences of renal
      tubule adenoma and renal tubule adenoma or carcinoma (combined) were
      significantly increased in males exposed to 1,800 ppm. The incidences of renal
      tubule hyperplasia were also significantly increased in all exposed groups of
      males. There was a positive trend in the incidences of mononuclear cell leukemia
      in males, and the incidence in the 1,800 ppm group was significantly increased.
      The incidence of adrenal medulla hyperplasia in the 1,800 ppm males was
      significantly increased. 2-YEAR STUDY IN MICE: Groups of 50 males and 50 females
      were exposed to methyl isobutyl ketone at concentrations of 0, 450, 900, or 1,800
      ppm by inhalation, 6 hours plus T(90) (12 minutes) per day, 5 days per week for
      105 weeks. Survival of males and females was similar to that of the chamber
      controls. The mean body weights of females exposed to 1,800 ppm were less than
      those of the chamber controls after week 17. The incidences of hepatocellular
      adenoma and hepatocellular adenoma or carcinoma (combined) were significantly
      increased in males and females exposed to 1,800 ppm. The incidences of
      eosinophilic foci were significantly increased in 450 and 1,800 ppm females.
      GENETIC TOXICOLOGY: Methyl isobutyl ketone was not mutagenic in Salmonella
      typhimurium strains TA97, TA98, TA100, or TA1535 when tested with and without
      hamster or rat liver metabolic activation enzymes. CONCLUSIONS: Under the
      conditions of these 2-year studies, there was some evidence of carcinogenic
      activity of methyl isobutyl ketone in male F344/N rats based on increased
      incidences of renal tubule neoplasms. Increased incidences of mononuclear cell
      leukemia in 1,800 ppm male F344/N rats may have been related to methyl isobutyl
      ketone exposure. There was equivocal evidence of carcinogenic activity of methyl
      isobutyl ketone in female F344/N rats based on the occurrence of renal
      mesenchymal tumors in the 1,800 ppm group. There was some evidence of
      carcinogenic activity of methyl isobutyl ketone in male and female B6C3F1 mice
      based on increased incidences of liver neoplasms. Exposure to methyl isobutyl
      ketone resulted in nonneoplastic lesions of the kidney characteristic of alpha2u
      globulin accumulation in male rats and nephropathy in female rats.

PMID- 17557117
TI  - Improved prediction of prostate cancer recurrence through systems pathology.
AB  - We have developed an integrated, multidisciplinary methodology, termed systems
      pathology, to generate highly accurate predictive tools for complex diseases,
      using prostate cancer for the prototype. To predict the recurrence of prostate
      cancer following radical prostatectomy, defined by rising serum prostate-specific
      antigen (PSA), we used machine learning to develop a model based on
      clinicopathologic variables, histologic tumor characteristics, and cell type
      specific quantification of biomarkers. The initial study was based on a cohort of
      323 patients and identified that high levels of the androgen receptor, as
      detected by immunohistochemistry, were associated with a reduced time to PSA
      recurrence. The model predicted recurrence with high accuracy, as indicated by a
      concordance index in the validation set of 0.82, sensitivity of 96%, and
      specificity of 72%. We extended this approach, employing quantitative multiplex
      immunofluorescence, on an expanded cohort of 682 patients. The model again
      predicted PSA recurrence with high accuracy, concordance index being 0.77,
      sensitivity of 77% and specificity of 72%. The androgen receptor was selected,
      along with 5 clinicopathologic features (seminal vesicle invasion, biopsy Gleason
      score, extracapsular extension, preoperative PSA, and dominant prostatectomy
      Gleason grade) as well as 2 histologic features (texture of epithelial nuclei and
      cytoplasm in tumor only regions). This robust platform has broad applications in
      patient diagnosis, treatment management, and prognostication.

PMID- 17557118
TI  - Regulation of iron homeostasis by the hypoxia-inducible transcription factors
      (HIFs).
AB  - Iron is essential for many biological processes, including oxygen delivery, and
      its supply is tightly regulated. Hepcidin, a small peptide synthesized in the
      liver, is a key regulator of iron absorption and homeostasis in mammals. Hepcidin
      production is increased by iron overload and decreased by anemia and hypoxia; but
      the molecular mechanisms that govern the hepcidin response to these stimuli are
      not known. Here we establish that the von Hippel-Lindau/hypoxia-inducible
      transcription factor (VHL/HIF) pathway is an essential link between iron
      homeostasis and hepcidin regulation in vivo. Through coordinate downregulation of
      hepcidin and upregulation of erythropoietin and ferroportin, the VHL-HIF pathway
      mobilizes iron to support erythrocyte production.

PMID- 17557119
TI  - Crucial role of the protein C pathway in governing microvascular inflammation in
      inflammatory bowel disease.
AB  - Endothelial protein C receptor (EPCR) and thrombomodulin (TM) are expressed at
      high levels in the resting microvasculature and convert protein C (PC) into its
      activated form, which is a potent anticoagulant and antiinflammatory molecule.
      Here we provide evidence that in Crohn disease (CD) and ulcerative colitis (UC),
      the 2 major forms of inflammatory bowel disease (IBD), there was loss of
      expression of endothelial EPCR and TM, which in turns caused impairment of PC
      activation by the inflamed mucosal microvasculature. In isolated human intestinal
      endothelial cells, administration of recombinant activated PC had a potent
      antiinflammatory effect, as demonstrated by downregulated cytokine-dependent cell
      adhesion molecule expression and chemokine production as well as inhibited
      leukocyte adhesion. In vivo, administration of activated PC was therapeutically
      effective in ameliorating experimental colitis as evidenced by reduced weight
      loss, disease activity index, and histological colitis scores as well as
      inhibited leukocyte adhesion to the inflamed intestinal vessels. The results
      suggest that the PC pathway represents a new system crucially involved in
      governing intestinal homeostasis mediated by the mucosal microvasculature.
      Restoring the PC pathway may represent a new therapeutic approach to suppress
      intestinal inflammation in IBD.

PMID- 17557120
TI  - MFG-E8-mediated uptake of apoptotic cells by APCs links the pro- and
      antiinflammatory activities of GM-CSF.
AB  - Granulocyte-macrophage colony-stimulating factor (GM-CSF) enhances protection
      against tumors and infections, but GM-CSF-deficient mice develop inflammatory
      disease. Here we show that GM-CSF is required for the expression of milk fat
      globule EGF 8 (MFG-E8) in antigen-presenting cells, and that MFG-E8-mediated
      uptake of apoptotic cells is a key determinant of GM-CSF-triggered tolerance and
      immunity. Upon exposure to apoptotic cells, GM-CSF-deficient antigen-presenting
      cells (APCs) produce an altered cytokine profile that results in decreased Tregs
      and increased Th1 cells, whereas concurrent ablation of IFN-gamma promotes Th17
      cells. In wild-type mice, MFG-E8 attenuates the vaccination activity of GM-CSF
      secreting tumor cells through Treg induction, whereas a dominant-negative MFG-E8
      mutant potentiates GM-CSF-stimulated tumor destruction through Treg inhibition.
      These findings clarify the immunoregulatory effects of apoptotic cells and
      suggest new therapeutic strategies to modulate CD4(+) T cell subsets in cancer
      and autoimmunity.

PMID- 17557121
TI  - Radiation and inhibition of angiogenesis by canstatin synergize to induce HIF
      1alpha-mediated tumor apoptotic switch.
AB  - Tumor radioresponsiveness depends on endothelial cell death, which leads in turn
      to tumor hypoxia. Radiation-induced hypoxia was recently shown to trigger tumor
      radioresistance by activating angiogenesis through hypoxia-inducible factor 1
      regulated (HIF-1-regulated) cytokines. We show here that combining targeted
      radioiodide therapy with angiogenic inhibitors, such as canstatin, enhances
      direct tumor cell apoptosis, thereby overcoming radio-induced HIF-1-dependent
      tumor survival pathways in vitro and in vivo. We found that following dual
      therapy, HIF-1alpha increases the activity of the canstatin-induced
      alpha(v)beta(5) signaling tumor apoptotic pathway and concomitantly abrogates
      mitotic checkpoint and tetraploidy triggered by radiation. Apoptosis in
      conjunction with mitotic catastrophe leads to lethal tumor damage. We discovered
      that HIF-1 displays a radiosensitizing activity that is highly dependent on
      treatment modalities by regulating key apoptotic molecular pathways. Our findings
      therefore support a crucial role for angiogenesis inhibitors in shifting the fate
      of radiation-induced HIF-1alpha activity from hypoxia-induced tumor
      radioresistance to hypoxia-induced tumor apoptosis. This study provides a basis
      for developing new biology-based clinically relevant strategies to improve the
      efficacy of radiation oncology, using HIF-1 as an ally for cancer therapy.

PMID- 17557123
TI  - Adaptations in the mandible and appendicular skeleton of high and low bone
      density inbred mice.
AB  - The appendicular skeletons of high [C3H/HeJ (C3H)] and low [C57BL/6J (B6)]
      density inbred mice have been shown to differ in morphology, mechanical
      properties, and cellular activity. The focus of the current study was to (1)
      characterize the mandibular bone formation rate (BFR/BS), bone mass, indentation
      modulus (IM), and hardness of C3H and B6 mice and (2) investigate the
      relationship of the mechanical properties in three skeletal sites: mandible,
      femur, and tibia. Specimens from 17-week-old female C3H and B6 (n = 15/group)
      mice were obtained. Mandibular bone mass was estimated from the lateral-view area
      (LVA) and transverse cross sections. BFR/BS was measured in the mandibular
      section distal to the third molar. In addition, bone blocks from the distal
      surface of the third molar and the femoral and tibial midshaft were obtained for
      mechanical testing. BFR/BS, cortical area, and LVA were greater (P < 0.001) in
      C3H mandibles. IM was approximately 2 GPa higher in the C3H mandible (P > 0.05),
      femur (P < 0.001), and tibia (P < 0.01). Mandibular IM was lower (P < 0.05) than
      the femoral and tibial IM within each inbred mouse. IM was not significant
      between C3H and B6 mandibles. However, the magnitude of the difference (
      approximately 12%) in the mandible was similar to the difference in the
      appendicular skeleton. This mandibular bone phenotype is similar to that observed
      in the appendicular skeleton of these distinct inbred mice.

PMID- 17557122
TI  - The phosphorylation state of eNOS modulates vascular reactivity and outcome of
      cerebral ischemia in vivo.
AB  - NO plays critical roles in vascular function. We show that modulation of the eNOS
      serine 1179 (S1179) phosphorylation site affects vascular reactivity and
      determines stroke size in vivo. Transgenic mice expressing only a phosphomimetic
      (S1179D) form of eNOS show greater vascular reactivity, develop less severe
      strokes, and have improved cerebral blood flow in a middle cerebral artery
      occlusion model than mice expressing an unphosphorylatable (S1179A) form. These
      results provide a molecular mechanism by which multiple diverse cardiovascular
      risks, such as diabetes and obesity, may be centrally integrated by eNOS
      phosphorylation in vivo to influence blood flow and cardiovascular disease. They
      also demonstrate the in vivo relevance of posttranslational modification of eNOS
      in vascular function.

PMID- 17557124
TI  - Cognition, psychosocial adjustment and coping in familial cases of
      velocardiofacial syndrome.
AB  - Velocardiofacial syndrome (VCFS) is characterized by both physical manifestations
      and neuropsychiatric disabilities. About 6-28% of cases are familial. The aim of
      the present study was to compare the clinical characteristics of subjects with
      familial and nonfamilial VCFS, with a special focus on cognitive and psychiatric
      disabilities. In addition, the complexities of coping with the disease in
      families in which both a parent and children are affected were highlighted in
      case vignettes. Sixteen patients from six families with VCFS were compared to 63
      subjects with nonfamilial VCFS for physical parameters, IQ, and rate of major
      psychiatric disorders. After controlling for the effect of age, IQ was
      significantly lower in the familial compared to the nonfamilial group of VCFS
      patients. Rate of psychiatric disorders was similarly high in both groups. The
      familial group had fewer cardiac and palate anomalies. A significant negative
      correlation was found between IQ and age. Most of the adults with familial VCFS
      were neuropsychiatrically disabled. Thus, although familial VCFS seems to be
      associated with a milder physical phenotype than nonfamilial VCFS, the
      neuropsychiatric deficits are significant in both types, at all ages.

PMID- 17557125
TI  - Cognitive demands and cortical control of human balance-recovery reactions.
AB  - A traditional view has been that balance control occurs at a very automatic
      level, primarily involving the spinal cord and brainstem; however, there is
      growing evidence that the cerebral cortex and cognitive processing are involved
      in controlling specific aspects of balance. The purpose of this review is to
      summarize recent literature pertaining to the cognitive demands and cortical
      control of balance-recovery reactions, focussing on five emerging sources of
      evidence: 1) dual-task studies demonstrating that concurrent performance of
      cognitive and balance-recovery tasks leads to interference effects; 2) dual-task
      studies that have examined the temporal dynamics associated with the reallocation
      of cognitive resources to the balance-recovery task; 3) visual attention studies
      that have inferred contributions of visual attention based on gaze measurements
      and/or manipulations to occlude vision; 4) measurements of brain potentials
      evoked by postural perturbation; and 5) use of transcranial magnetic stimulation
      to alter contributions from specific cortical areas.

PMID- 17557127
TI  - Aniracetam restores the effects of amyloid-beta protein or ageing on membrane
      fluidity and intracellular calcium concentration in mice synaptosomes.
AB  - In the present study, we observed the in vitro effect of aniracetam on membrane
      fluidity and free calcium concentrations ([Ca(2+)]i) of frontal cortical (FC) and
      hippocampal (HP) synaptosomes of aged mice and young mice treated with amyloid
      beta protein (Abeta) Membrane fluidity was measured by using fluorescence
      anisotropy of the lipophilic probe, 1,6-diphenyl-1,3,5-hexatriene (DPH).
      [Ca(2+)]i was measured by using Fura 2-AM fluorescent spectrophotometry. We found
      that membrane fluidity of the FC and HP synaptosomes was decreased in 14 months
      old mice compared with that in 3 months old mice. Similarly, Abeta25-35 (1
      microM) decreased the membrane fluidity in 3 months old mice. These effects of
      ageing and Abeta25-35 on membrane fluidity were restored by aniracetam in a
      concentration-dependent manner. Furthermore, Abeta25-35 (1 microM) largely
      increased [Ca(2+)]i in FC and HP synaptosomes in 3 months old mice, but this
      effect on HP synaptosomes was effectively reversed by aniracetam (1-4 mM). The
      present findings suggest that aniracetam restores age- and Abeta-induced
      alterations in membrane fluidity or Abeta-induced increase in [Ca(2+)]i,
      demonstrating a possible beneficial role of aniracetam in the clinic treatment
      for senile dementia or Alzheimer's disease.

PMID- 17557126
TI  - Developmental pattern changes of prefrontal efferents in the juvenile gerbil
      (Meriones unguiculatus).
AB  - Previous findings of our group showed that early traumatisation leads to a
      dysfunctional organisation of prefrontocortical efferents in adulthood. To
      identify vulnerable time windows during maturation, we labelled either layer III-
      or layer V/VI-pyramidal cells with biocytin in the prefrontal cortex of gerbils
      (Meriones unguiculatus) from the age of postnatal day (PD) 15 up to adulthood (PD
      90). The density of passing fibres and axonal terminals in distinct cortical
      columns in specific prefrontal projection areas was assessed by digital image
      analysis. Following layer III injections, fibre densities reached adult values
      between adolescence (PD 60) and adulthood (PD 90). However, layer V/VI-fibre
      densities decreased after eye-opening (PD 15), followed by an increase to adult
      values after weaning (PD 30). These findings are the first to describe dynamic
      structural changes even beyond adolescence of functionally diverse prefrontal
      output systems. External interventions might exert adverse influences on the
      establishment of integrated prefrontal networks especially during the early phase
      of re-arranging.

PMID- 17557128
TI  - Future aspects of botulinum neurotoxins.
AB  - The future of botulinum neurotoxin (BoNT) development is expected to proceed
      along two lines: the development of novel indications and the development of
      novel products. New indications will likely be based on the neuromuscular mode of
      action of BoNTs, as well as action on primary sensory fibers and other neuronal
      types. Novel BoNT products may be designed for increased specificity or enhanced
      duration. As new products enter the market, it will be important for each to
      demonstrate efficacy and safety. Unfortunately, the future of BoNTs will also
      likely include attempts to obtain and distribute unlicensed and illegal BoNT
      products that may pose substantial risks to patients.

PMID- 17557129
TI  - Olanzapine potentiates neuronal survival and neural stem cell differentiation:
      regulation of endoplasmic reticulum stress response proteins.
AB  - Recent clinical neuroimaging studies have suggested that morphological brain
      changes occur and progress in the course of schizophrenia. Although the
      neurogenetic and neurotrophic effects of antipsychotics are considered to
      contribute to the prevention of reduction in brain volume, the cellular molecular
      mechanisms of action of antipsychotics have not yet been elucidated. We examined
      the effects of antipsychotics on the endoplasmic reticulum (ER) stress-induced
      damages of neurons and neural stem cells (NSCs) using cultured cells. In the
      neuronal cultures, the atypical antipsychotic olanzapine protected neurons from
      thapsigargin (1 microM)-induced injury. It was observed that a low concentration
      of thapsigargin (10 nM) that did not affect the neuronal survival could reduce
      neuronal differentiation of cultured NSCs, suggesting a role of ER stress in the
      differentiation function of NSCs. Treatment with olanzapine increased the
      neuronal differentiation suppressed by the exposure to thapsigargin (10 nM). The
      thapsigargin-induced ER chaperones, GRP78, which indicate the ER stress condition
      of the cell, were decreased by the treatment with the atypical antipsychotics
      olanzapine and quetiapine but not by the typical antipsychotic haloperidol. These
      results indicate that the amelioration of ER-stress might be involved in the
      cellular mechanisms of atypical antipsychotics to produce neuroprotective and
      neurogenetic actions in neurons and NSCs, suggesting potential roles of these
      drugs for treatment of schizophrenia.

PMID- 17557130
TI  - Prevention of falls in older people with dementia.
AB  - Falls are a major cause of morbidity and mortality in older people with dementia.
      However, although we know that people with dementia can comply with interventions
      known to reduce falls in cognitively normal populations, and that these
      interventions can modify certain risk factors for falls in patients with
      dementia, direct evidence that falls can be prevented in older people with
      dementia is lacking. Further research is required specifically targeting fall
      prevention in older people with dementia.

PMID- 17557132
TI  - Group A rotavirus genotypes in Germany during 2005/2006.
AB  - During the 2005/2006 winter season a total of 802 group A positive rotavirus
      specimens of patients from different regions throughout Germany were genotyped.
      Amplicons from a one-tube RT-PCR were typed by analysis of their (type-specific)
      size using type-specific primers, fluorescent consensus primers and a capillary
      sequencer for detection. While G1P[8] was predominant (45.8%), G9P[8] has emerged
      as the second most frequent genotype combination (37.7%). The distribution of
      genotypes was heterogeneous, regional frequencies regarding G1 and G9 were
      ranging from 15.0 to 89.3% and from 7.1 to 67.7%, respectively. Furthermore, a
      few human rotavirus G10P[6] and G10P[8] infections were observed.

PMID- 17557131
TI  - Non-pharmacologic prevention of Alzheimer's disease: nutritional and life-style
      risk factors.
AB  - We conducted a review of cohort studies and interventional studies on nutritional
      and life-style risk factors and primary prevention of Alzheimer's Disease.
      Studies were assessed by the Oxford classification. Interventional studies exist
      for mental training and vitamin supplementation. For alcohol, fat and fish
      intake, mediterranean diet, homocysteine, overweight/caloric intake, physical and
      social activity, hypercholesterolemia, diabetes and smoking, currently there is
      only evidence from cohort studies. Cognitive stimulation by mental training
      increases mental functions and can be recommended on the basis of positive
      interventional studies. Vitamin supplementation cannot prevent AD on the basis of
      interventional studies. Hyperlipidemia, hyperhomocysteinemia, diabetes and
      typical life-style factors (alcohol, smoking, obesity etc.) modestly increased AD
      risk, fish, mediterranean diet and unsaturated fat or n-3 fatty acids and social
      activity are protective in observational cohorts, but interventional studies are
      lacking.

PMID- 17557133
TI  - Sequence determination of variable regions within the genomes of gallid
      herpesvirus-2 pathotypes.
AB  - Comparative genomic studies of attenuated and virulent strains of Gallid
      herpesvirus 2 (GaHV-2) have identified 6 regions of sequence variability. These
      regions include the open reading frames (ORFs) encoding UL36 and UL49 and regions
      devoid of large ORFs (132-bp repeats, a-like sequences and the junctions flanking
      the unique short region). Our data indicate that the carboxyl terminus of UL36
      contains regions of heterogeneity that are unique to CVI988-derived attenuated
      strains. A deletion of the TKSERT domain and a glycine(245) polymorphism in the
      UL49 proteins were also identified in these derivatives. Phylogenetic analyses of
      both UL36 and UL49 sequences indicate that CVI988-derived strains partition
      differently from other attenuated strains (RM-1 and R2/23), indicating that
      additional mutations contribute to attenuation. In very virulent and very
      virulent plus strains a single nucleotide polymorphism (SNP) was identified
      within the 132-bp tandem repeats. Within the junctions flanking the unique short
      region, these strains also contain deletions in sequences that are predicted to
      bind the transcription factor NF kappaB. In some attenuated strains, deletions
      were also identified in the latency-associated transcript (LAT) promoters and
      adjacent regions encoding microRNAs. These results indicate that virulence is
      likely multi-factorial with contributions from both multiple genes and cis-acting
      sites.

PMID- 17557134
TI  - Comparisons of the complete genomes of two Chinese isolates of a recent foot-and
      mouth disease type Asia 1 virus.
AB  - China reported the first outbreak of foot-and-mouth disease (FMD) serotype Asia 1
      in Chinese Hong Kong in March, 2005. Subsequently, this type of the virus was
      reported from mainland of China in April 2005. Up to September of 2006, it was
      detected in more than 15 areas of China. In this paper, the complete genomes of
      two Chinese isolates, Asia 1/HNK/CHA/05 and Asia 1/JS/CHA/05, of foot-and-mouth
      disease virus (FMDV) were sequenced and compared with some Chinese sequences and
      reference sequences from other countries. The identities between Asia
      1/HNK/CHA/05 and Asia 1/JS/CHA/05 of 5'-UTR, L gene, P1 (VP1) gene, P2 gene, P3
      gene, 3'-UTR are 84.8, 87.6, 86.4 (82.3%), 92.5, 92.8 and 95.3%, respectively.
      The data revealed that these two strains do not belong to the same genotype
      depending on the analysis of VP1 sequences, and neither of them have deleted
      bases in 5'UTR and 3A genes compared with the reference sequences. In addition,
      the secondary structures of their 5'UTR and 3'UTR are discussed.

PMID- 17557135
TI  - Functional characterization of chitinase from Cydia pomonella granulovirus.
AB  - Baculovirus chitinases (V-CHIAs) play a crucial role in the terminal liquefaction
      of virus-infected larvae after death. Although v-chiAs from
      nucleopolyhedroviruses (NPVs) have been well characterized, little is known about
      v-chiAs from granuloviruses (GVs). We characterized the v-chiA of Cydia pomonella
      GV (CpGV) by constructing a recombinant Bombyx mori NPV (BmNPV) in which BmNPV v
      chiA was replaced by CpGV v-chiA (103CpGV virus). CpGV v-chiA encoded an
      approximately 70-kDa chitinase with an exo-type substrate preference. CpGV V-CHIA
      lacked a C-terminal KDEL endoplasmic reticulum retention motif and was suggested
      to be a secretory protein. Terminal host liquefaction of B. mori larvae and
      proper folding of BmNPV-encoded cysteine protease (BmNPV V-CATH) were observed
      following infection with 103CpGV, indicating that CpGV v-chiA is able to
      compensate for the absence of its BmNPV counterpart. Our data suggest that the
      molecular interaction between V-CHIA and V-CATH may be conserved across a broad
      range of lepidopteran GVs and NPVs.

PMID- 17557136
TI  - Trastuzumab prolongs overall survival in patients with brain metastases from Her2
      positive breast cancer.
AB  - BACKGROUND: Brain metastases are frequently encountered in Her2 positive advanced
      breast cancer. It is still not clear, if trastuzumab treatment should be
      continued following their diagnosis. In this analysis we evaluated if trastuzumab
      was able to influence time to in-brain progression (TTP) and overall survival
      (OS). For this reason, we compared patients who continued on trastuzumab with a
      historical control group. PATIENTS AND METHODS: Seventeen Her2 positive patients
      receiving whole brain radiotherapy for brain metastases and continuing on
      trastuzumab were identified. As historical control group, thirty-six patients
      treated before 2002 were identified from a breast cancer database. We performed a
      multivariate analysis (Cox regression) to explore which factors were potentially
      able to significantly influence TTP and OS. RESULTS: Median TTP was 6 months,
      range 1-33+ months. Median OS was 7 months, range 1-38 months. Seventeen patients
      received trastuzumab after WBRT. Factors associated with prolonged TTP were KPS
      (p = 0.001), and intensified local treatment (p = 0.004). A trend towards longer
      TTP was observed in patients treated with trastuzumab (p = 0.068). OS was
      significantly influenced by KPS (p < 0.001), and continued antibody therapy (p =
      0.001). CONCLUSION: Two parameters were significantly associated with prolonged
      OS: KPS and trastuzumab. While there was a trend towards prolonged TTP in
      patients with trastuzumab treatment after WBRT, this did not reach statistical
      significance. It appears therefore reasonable to suggest continuation of antibody
      therapy in patients with good performance status despite disease spreading to the
      brain. Concerning activity of trastuzumab in brain metastases themselves, no
      final conclusion is possible.

PMID- 17557138
TI  - Primary single-plate Molteno tube implantation for management of glaucoma in
      children with Sturge-Weber syndrome.
AB  - PURPOSE: To evaluate the safety and efficacy of primary single-plate Molteno tube
      implantation in the management of childhood glaucoma associated with Sturge-Weber
      syndrome. PATIENTS AND METHODS: Nine eyes of seven patients were included in this
      prospective case series. Success was defined as intraocular pressure (IOP) < or
      =22 mmHg with (relative success) or without (absolute success) glaucoma
      medications. Intra- and postoperative complications were also evaluated. RESULTS:
      Mean age at the time of the surgery was 9.6 +/- 3.7 years (range: 5-17 years) and
      mean follow-up duration was 32 +/- 4.7 months (range: 20-36 months). Mean IOP was
      reduced from 34.2 +/- 8.3 mmHg preoperatively to 21.2 +/- 7.3 mmHg at the final
      follow-up (P = 0.012). The number of anti-glaucoma medications was reduced from
      3.4 +/- 0.5 preoperatively to 2.2 +/- 1.3 at the final follow-up (P = 0.058). The
      cumulative probability of relative success was 97.2% [95% confidence interval
      (CI): 91.85-100%] at 12 months, 78.02% (95% CI: 60.36-95.67%) at 24 months and
      43.34% (95% CI: 16.18-70.5%) at the final follow-up. During the first 6 months
      after surgery, two patients had controlled IOP without the use of medications
      (absolute success); however, 6 months and later no eye had achieved absolute
      success. There were no intraoperative complications. Postoperative complications
      included choroidal effusion necessitating drainage in three eyes (33.3%),
      cataract formation in one eye (11%) and retinal detachment in one eye (11%). At
      the final follow-up, visual acuity was unchanged from preoperative values in five
      eyes (55.5%); no eye demonstrated visual improvement. CONCLUSION: Outcomes of
      this small case study reveal that primary single-plate Molteno tube implantation
      appears to be associated with a limited success rate and a relatively high
      complication rate in eyes of children with glaucoma resulting from Sturge-Weber
      syndrome.

PMID- 17557137
TI  - Hyperoxia retards growth and induces apoptosis, changes in vascular density and
      gene expression in transplanted gliomas in nude rats.
AB  - This study describes the biological effects of hyperoxic treatment on BT4C rat
      glioma xenografts in vivo with special reference to tumor growth, angiogenesis,
      apoptosis, general morphology and gene expression parameters. One group of tumor
      bearing animals was exposed to normobaric hyperoxia (1 bar, pO(2) = 1.0) and
      another group was exposed to hyperbaric hyperoxia (2 bar, pO(2) = 2.0), whereas
      animals housed under normal atmosphere (1 bar, pO(2) = 0.2) served as controls.
      All treatments were performed at day 1, 4 and 7 for 90 min. Treatment effects
      were determined by assessment of tumor growth, vascular morphology
      (immunostaining for von Willebrand factor), apoptosis by TUNEL staining and cell
      proliferation by Ki67 staining. Moreover, gene expression profiles were obtained
      and verified by real time quantitative PCR. Hyperoxic treatment caused a
      approximately 60% reduction in tumor growth compared to the control group after 9
      days (p < 0.01). Light microscopy showed that the tumors exposed to hyperoxia
      contained large "empty spaces" within the tumor mass. Moreover, hyperoxia induced
      a significant increase in the fraction of apoptotic cells ( approximately 21%),
      with no significant change in cell proliferation. After 2 bar treatment, the mean
      vascular density was reduced in the central parts of the tumors compared to the
      control and 1 bar group. The vessel diameters were significantly reduced (11-24%)
      in both parts of the tumor tissue. Evidence of induced cell death and reduced
      angiogenesis was reflected by gene expression analyses.Increased pO(2)-levels in
      experimental gliomas, using normobaric and moderate hyperbaric oxygen therapy,
      caused a significant reduction in tumor growth. This process is characterized by
      enhanced cell death, reduced vascular density and changes in gene expression
      corresponding to these effects.

PMID- 17557139
TI  - Smoking and environmental iodine as risk factors for thyroiditis among parous
      women.
AB  - OBJECTIVE: To elucidate whether exposure to some environmental factors, i.e.
      cigarette smoking and iodine deficiency influence the risk of thyroiditis.
      METHODS: We identified a cohort of 874, 507 parous women with self-reported
      information on smoking during pregnancy registered in the Swedish Medical Birth
      Registry from September 1983 through December 1997. Hospital diagnoses of
      thyroiditis (n = 286) and hypothyroidism (n = 690) following entry into the
      cohort were identified by record-linkage with the national Inpatient Registry.
      The hazard ratio (HR) of smokers compared to non-smokers and the corresponding
      95% confidence limits (CL) were estimated by Cox regression. RESULTS: Smoking was
      inversely associated with risk of overt thyroiditis (adjusted HR = 0.72; CL =
      0.54-0.95), even when diagnoses of primary hypothyroidism were included. However,
      a diagnosis of thyroiditis within 6 months from a childbirth was positively
      associated with smoking (adjusted HR = 1.88; CL = 0.94-3.76). Being born in areas
      of endemic goiter was not associated to hospital admission for thyroiditis.
      Thyroiditis patients who were smokers had more often than non-smokers a co
      morbidity with other autoimmune disorders. CONCLUSIONS: Smoking may increase the
      risk of thyroiditis occurring in the post-partum period and influence the
      clinical expression of other thyroiditis, especially when occurring as part of a
      polymorphic autoimmune disease.

PMID- 17557140
TI  - Comparison of relative and attributable risk of myocardial infarction and stroke
      according to C-reactive protein and low-density lipoprotein cholesterol levels.
AB  - C-reactive protein (CRP) was proposed as a stronger predictor of cardiovascular
      events than low-density lipoprotein cholesterol (LDL-C); however, these
      associations may differ between myocardial infarction (MI) and stroke. We
      compared statistically the associations of CRP and LDL-C levels with risk of MI
      versus stroke and examined to what extent consideration of CRP or LDL-C increases
      the population attributable fractions (PAFs) of MI and stroke beyond traditional
      risk factors among 27,548 subjects from the European Prospective Investigation
      into Cancer and Nutrition-Potsdam Study in a case-cohort design. Among subjects
      without prior MI or stroke, 156 developed MI and 132 stroke during 6.0 years of
      follow-up. In adjusted competing risk analyses CRP was positively related to MI
      and stroke (P difference between endpoints = 0.55), whereas LDL-C was related to
      MI but not stroke (P difference between endpoints = 0.003). The PAF for smoking,
      diabetes, and hypertension combined was 0.76 for MI, and 0.58 for stroke. With
      additional consideration of CRP the PAFs were 0.80 and 0.68, while with addition
      of LDL-C the PAFs were 0.88 and 0.55. We conclude that CRP is equally strongly
      related to risk of MI and stroke, whereas LDL-C is related to risk of MI but not
      stroke. Consideration of LDL-C beyond smoking, diabetes and hypertension may
      increase the PAF of MI slightly more than CRP. In contrast, consideration of CRP
      but not of LDL-C may increase the PAF of stroke beyond these factors.

PMID- 17557142
TI  - Selected technologies to control genes and their products for experimental and
      clinical purposes.
AB  - "On-demand" regulation of gene expression is a powerful tool to elucidate the
      functions of proteins and biologically-active RNAs. We describe here three
      different approaches to the regulation of expression or activity of genes or
      proteins. Promoter-based regulation of gene expression was among the most rapidly
      developing techniques in the 1980s and 1990 s. Here we provide basic information
      and also some characteristics of the metallothionein-promoter-based system, the
      tet-off system, Muristerone-A-regulated expression through the ecdysone response
      element, RheoSwitch, coumermycin/novobiocin-regulated gene expression, chemical
      dimerizer-based promoter activation systems, the "Dual Drug Control" system,
      "constitutive androstane receptor"-based regulation of gene expression, and
      RU486/mifepristone-driven regulation of promoter activity. A large part of the
      review concentrates on the principles and usage of various RNA interference
      techniques (RNAi: siRNA, shRNA, and miRNA-based methods). Finally, the last part
      of the review deals with historically the oldest, but still widely used, methods
      of temperature-dependent regulation of enzymatic activity or protein stability
      (temperature-sensitive mutants). Due to space limitations we do not describe in
      detail but just mention the tet-regulated systems and also fusion-protein-based
      regulation of protein activity, such as estrogen-receptor fusion proteins. The
      information provided below is aimed to assist researchers in choosing the most
      appropriate method for the planned development of experimental systems with
      regulated expression or activity of studied proteins.

PMID- 17557141
TI  - AHSG gene polymorphisms are associated with bone mineral density in Caucasian
      nuclear families.
AB  - PURPOSE: To investigate the role of alpha2-HS glycoprotein (AHSG) gene on bone
      mineral density (BMD) variation. METHODS: A total of 665 subjects from 157
      Caucasian nuclear families were genotyped at the AHSG NlaIII, SacI sites. The
      association and linkage between the single SNP markers and haplotypes constructed
      by two markers in this gene and BMDs at the spine and hip were determined by
      using quantitative transmission disequilibrium test (QTDT). RESULTS: Significant
      within-family associations were obtained for spine BMD at both of studied markers
      (P = 0.036 and 0.005 at the NlaIII and SacI sites, respectively). Significant (P
      = 0.008 at the NlaIII locus) (P = 0.004 at the SacI locus) total associations at
      spine BMD were detected. Haplotype analyses confirmed those within-family and
      total association. CONCLUSIONS: These data suggest the polymorphisms in the AHSG
      gene may have effects on BMD variation in Caucasian population.

PMID- 17557143
TI  - Trafficking of FoxP3+ regulatory T cells: myths and facts.
AB  - Fork head box P3 (FoxP3(+)) regulatory T cells (Tregs) are specialized T cells
      for prevention of hyperimmune responses and autoimmunity. Tumors and pathogens
      can hijack FoxP3(+) Tregs to evade host immune responses. There is an increasing
      body of evidence that trafficking of FoxP3(+) Tregs is important for their
      effective suppression of target cells. Because of their distinctive functions and
      gene expression phenotype, the migratory behavior of FoxP3(+) Tregs has been
      somewhat mystified. The myths are that they have unique trafficking receptors and
      migratory behaviors that are different from those of conventional T cells.
      Another related myth is that FoxP3(+) regulatory T cell subsets have a fixed
      trafficking behavior from the time they are generated in the thymus. The recent
      progress in trafficking receptors and migratory behavior of FoxP3(+) Tregs is
      reviewed here and the validity of these myths is examined.

PMID- 17557144
TI  - The innate cellular responses to HIV-1 invasion: emerging molecules of ancient
      defense mechanisms.
AB  - Along alternative protective pathways, human cells can synthesize biologically
      active proteins that interfere with HIV replication, but are not viral antigen
      specific. HIV is sensitive to several viral inhibitors of cellular origin, such
      as interferons or interferon-regulated proteins. With the progress of AIDS
      research it has become evident that the immune cells of some individuals are
      capable of restricting the virus by secretion of other, yet unidentified
      factor(s) that can be detected only by their potent antiviral activity. Research
      efforts to identify this inhibitor of HIV--a "magic bullet" released by our
      immune cells--have revealed the identity of several novel molecules and added to
      the knowledge of innate cellular responses to viral invasion.

PMID- 17557145
TI  - M cells are involved in pathogenesis of human contact lens-associated giant
      papillary conjunctivitis.
AB  - INTRODUCTION: The objective was to study the pathogenesis of contact lens
      associated giant papillary conjunctivitis (CL-GPC). MATERIALS AND METHODS: Twenty
      one biopsies of conjunctival giant papillae were obtained from soft contact lens
      wearers. The tissues were fixed in 4% paraformaldehyde and embedded in paraffin.
      Sections of 5 microm thickness were used for studies of histology and
      immunohistochemistry of pan-B and pan-T cell distributions. RESULTS: Conjunctival
      epitheliums on the top of conjunctiva-associated lymphoid tissue typically lacked
      goblet cells. Lymphocytes from underlying lymphoid follicle were pressed into
      intra-epithelial "pockets" formed through epithelial invagination. Under the
      follicle-associated epithelium, pan-B cells were mostly gathered in the central
      follicular area and intraepithelial pockets, while CD3-positive T cells were
      predominantly distributed in parafollicular region, but only a few in the
      intraepithelial pockets. CONCLUSIONS: Membranous epithelial cells (M cells) play
      a key role in the pathogenesis of CL-GPC for the binding and translocation of
      antigen and pathogen.

PMID- 17557146
TI  - Skin-induced tolerance and its reversal by Toll-like receptor ligands.
AB  - In 1970, Gershon was the first to propose that T cells, in addition to their
      helper activity, can also play a role as regulatory cells capable of suppressing
      immune responses. However, the initial strong interest in T cell-mediated
      suppression was followed by a period of doubt and skepticism. Since the late 1990
      s the "S" word started to be used in immunology again and interest in T
      suppressor cells has grown, ushering in a new renaissance for the field. In this
      article the author presents the current knowledge about a new subject called
      "skin-induced tolerance". Suppression is induced via epicutaneous immunization
      and is described in both Th1- and Tc1-mediated contact sensitivity reactions. The
      subject of skin-induced tolerance is also considered in the regulation of
      experimental models of autoimmune diseases such as allergic autoimmune
      encephalomyelitis and collagen-induced arthritis and finally in an animal model
      of graft rejection. The last part of this presentation will introduce the very
      fresh subject of "contrasuppression", or the reversal of skin-induced
      suppression.

PMID- 17557147
TI  - Serological classification and epitope specificity of Proteus vulgaris TG 251
      from Proteus serogroup O65.
AB  - INTRODUCTION: Proteus rods are currently subdivided into five named species, i.e.
      Proteus mirabilis, P. vulgaris, P. penneri, P. hauseri, and P. myxofaciens, and
      three unnamed Proteus genomospecies 4 to 6. Based on the serospecificity of the
      lipopolysaccharide (LPS; O-antigen), strains of P. mirabilis and P. vulgaris were
      divided into 49 O-serogroups and 11 additional O-serogroups were proposed later.
      About 15 further O-serogroups have been proposed for the third medically
      important species, P. penneri. Here the serological classification of P. vulgaris
      strain TG 251, which does not belong to these serogroups, is reported.
      Serological investigations also allowed characterization of the epitope
      specificity of its LPS. MATERIALS AND METHODS: Purified LPSs from five Proteus
      strains were used as antigens in enzyme immunosorbent assay (EIA), SDS/PAGE, and
      Western blot and alkali-treated LPSs in the passive immunohemolysis (PIH) test,
      inhibition of PIH and EIA, and absorption of the rabbit polyclonal O-antisera
      with the respective LPS. RESULTS: The serological studies of P. vulgaris TG 251
      LPS indicated the identity of its O-polysaccharide with that of P. penneri O65.
      The antibody specificities of P. vulgaris TG 251 and P. penneri O65 O-antisera,
      were described. CONCLUSIONS: P. vulgaris TG 251 was classified to the Proteus O65
      serogroup. Two disaccharide-associated epitopes present in P. vulgaris TG 251 and
      P. penneri O65 LPSs are suggested to be responsible for cross-reactions with
      three heterologous Proteus strains.

PMID- 17557148
TI  - Comparison of two methods used for monitoring low-copy cytomegalovirus infection
      in a patient with chronic myeloid leukemia after unrelated umbilical cord blood
      transplantation.
AB  - INTRODUCTION: Detection of human cytomegalovirus (CMV, HHV-5) DNA in clinical
      specimens is considered a cornerstone in the diagnosis of HHV-5 disease. The
      present study compared two quantitative methods used for diagnosing
      cytomegalovirus infection in a 21-year-old woman with chronic myeloid leukemia
      after an unrelated umbilical cord blood transplantation. MATERIALS AND METHODS:
      Blood samples were tested for the presence of HHV-5 DNA using the LightCycler
      PCR, the quantitative Eclipse CMV DNA Detection Kit, and a qualitative in-house
      PCR assay using primers that amplify part of the HHV-5 MIE gene. RESULTS: Results
      from samples containing a low cytomegalovirus load were more accurate with the
      LightCycler test than those obtained with the Eclipse test, which underestimated
      the viral load of samples containing low DNA copy numbers. CONCLUSIONS: These
      findings underline the value of novel PCR methods used in current therapeutic
      procedures and in monitoring antiviral therapy with nucleoside analogs. The high
      level of sensitivity, specificity, accuracy, and rapidity provided by the
      LightCycler instrument are favorable for the use of this system in the detection
      of HHV-5 DNA in clinical specimens.

PMID- 17557149
TI  - Effect of structural modification at the 4, 3', and 2' positions of doxorubicin
      on topoisomerase II poisoning, apoptosis, and cytotoxicity in human melanoma
      cells.
AB  - INTRODUCTION: The mechanism of the cytotoxicity of anthracyclines is pleiotropic
      and its significance in cell growth inhibition seems to be highly specific and
      dependent on cell type and anthracycline drug. Resistance and the high
      cardiotoxicity of anthracyclines have stimulated many studies aimed at
      identifying critical substituents required for optimal activity. Many authors
      point to the fact that the double-strand breaks, the consequence of the activity
      of topoisomerase II poisons, and the inability of cells to repair the DNA lesions
      are the signal for apoptosis. The aim of this study was to define the influence
      of 4-demetoxy 2'-halogenated analogs with altered basicity at the 3'-position on
      topoisomerase II and the relationship of that interaction with apoptosis and the
      cytotoxicity of these novel anthracyclines. Parental human ME18 melanoma cells
      and the ME18/R subline, obtained experimentally, resistant to doxorubicin (DOX),
      exposed to 1.7 and 8.6 microM DOX or its analogs, annamycin and WP903 (both 0.3
      and 3.0 microM) were studied. MATERIALS AND METHODS: The MTT test was used to
      assay cytotoxicity. Interaction of the drugs with topoisomerase II and apoptosis
      were done by Western blot and fluorescence microscopy using Hoechst 33342.
      RESULTS: The structural changes at positions 4, 2', and 3' can influence
      topoisomerase II interaction and apoptotic activity, although correlation between
      these events and cytotoxic consequences has not been proved. CONCLUSIONS: The
      biological response of the cells to the structurally similar anthracyclines may
      be variable and probably depends on the cell type which seems to be an additional
      problem in the multifactorial resistance of tumor cells to anthracyclines.

PMID- 17557150
TI  - Vascular endothelial growth factor in systemic lupus erythematosus: relationship
      to disease activity, systemic organ manifestation, and nailfold capillaroscopic
      abnormalities.
AB  - INTRODUCTION: The aim of the study was to evaluate whether vascular endothelial
      growth factor (VEGF) serum level is associated with systemic organ involvement,
      microvascular changes as determined by nailfold capillaroscopy, and disease
      activity of systemic lupus erythematosus (SLE). MATERIALS AND METHODS: Serum
      levels of VEGF were determined by an enzyme-linked immunosorbent assay in 47 SLE
      patients and in 30 healthy controls. Nailfold capillaroscopy was performed in all
      patients and healthy subjects. RESULTS: Morphological changes were observed by
      nailfold capillaroscopy in 45 of 47 (95.7%) SLE patients. Mild capillary changes
      were found in 16 (34%), moderate in 21 (44.7%), and severe in 8 (17%) SLE
      patients. All patients with systemic organ involvement showed severe or moderate
      changes in nailfold capillaroscopy. In comparison with the control group, a
      higher serum concentration of VEGF in SLE patients was demonstrated (p<0.05).
      Furthermore, significant differences in VEGF serum concentration between SLE
      patients with systemic involvement and controls were found (p<0.01). Comparison
      between patients with active and inactive SLE according to SLEDAI score showed a
      significantly higher concentration of VEGF in the sera of patients with active
      SLE (p<0.01). The SLE patients with severe and moderate changes in nailfold
      capillaroscopy showed significantly higher VEGF serum levels than SLE patients
      with mild changes (p<0.05) or healthy controls (p<0.01). Moreover, the VEGF serum
      level correlated significantly with ESR (r=0.580, p<0.0001) and CRP (r=0.512,
      p<0.005). CONCLUSIONS: Our data suggest that VEGF serum level may be a useful
      marker of disease activity and internal organ involvement in SLE patients.
      Abnormalities in nailfold capillaroscopy may reflect the extent of microvascular
      involvement and are associated with systemic manifestation in SLE.

PMID- 17557152
TI  - Determination of sub-ppb reserpine by an optosensing device based on
      photochemically induced fluorescence.
AB  - A flow injection-solid-phase spectroscopy (FI-SPS) system implemented with
      photochemically induced fluorescence (PIF) is described for the rapid and very
      sensitive determination of reserpine in biological fluids and pharmaceutical
      formulations. An intensively fluorescent photoproduct is in-line generated,
      retained on C18 silica gel in the detection area and monitored at 394/489 nm
      (lambdaex/lambdaem). After the establishment of the appropriate working
      variables, the system is calibrated at two different injection volumes, 100 and
      800 microL, achieving detection limits of 0.33 and 0.05 ng mL(-1), respectively.
      The RSD for reserpine at 2 ng mL(-1) (800 microL) was 1.5% (n=10). The sampling
      rates were 46 and 43 h(-1) for each injection volume, respectively. The potential
      interference of some common species coexisting with reserpine in the analysed
      samples was also studied. The procedure was successfully applied to commercial
      formulations, urine and serum without any previous treatment of samples.
      Recoveries ranged from 94.9 to 100.2%.

PMID- 17557151
TI  - Cortico-limbic circuitry for conditioned nicotine-seeking behavior in rats
      involves endocannabinoid signaling.
AB  - RATIONALE: The endocannabinoid system plays an important role in conditioned drug
      seeking, but the neuronal mechanisms involved in this behavior are unclear.
      OBJECTIVES: Here, we evaluate the role of endogenous cannabinoids in the cortico
      limbic circuitry in cue-induced nicotine-seeking behavior in rats. METHODS:
      Animals were first trained to self-administer nicotine (0.03 mg/kg/injection, IV)
      under conditions in which responding was reinforced jointly by response
      contingent nicotine injections and audiovisual stimuli. During subsequent
      sessions, nicotine was withdrawn and responding was reinforced by contingent
      presentation of the stimuli only. One month after nicotine removal, the
      cannabinoid CB1 receptor antagonist, rimonabant, was injected bilaterally into
      the shell of the nucleus accumbens (ShNAcc, 0.3, 3, or 30 ng/0.5 microl), the
      basolateral amygdala (BLA, 30 ng/0.5 microl), or the prelimbic cortex (PLCx, 30
      ng/0.5 microl). RESULTS: Rimonabant injected into the ShNAcc dose-dependently
      reduced nicotine-seeking behavior without modifying spontaneous locomotor
      activity. Similar results were obtained when the drug (30 ng) was injected into
      the BLA or the PLCx. The anatomical specificity was confirmed in a control
      experiment using [(3)H]rimonabant. Fifteen minutes after drug injection, when the
      behavioral effects of rimonabant were already achieved, radioactivity was
      detected at the site of injection and had not diffused to adjacent regions.
      CONCLUSIONS: These findings demonstrate that increased endocannabinoid
      transmission critically triggers conditioned nicotine-seeking behavior in key
      cortico-limbic regions.

PMID- 17557153
TI  - Growth cone response to ephrin gradients produced by microfluidic networks.
AB  - A microfluidic network (microFN) etched into a silicon wafer was used to deliver
      protein solutions containing different concentrations of the axonal guidance
      molecule ephrinA5 onto a silicone stamp. In a subsequent microcontact printing
      (microCP) step, the protein was transferred onto a polystyrene culture dish. In
      this way, stepwise substrate-bound concentration gradients of ephrinA5 were
      fabricated spanning a total distance of 320 microm. We tested the response of
      chick retinal ganglion cell (RGC) axons, which are guided in vivo by ephrin
      gradients, to these in vitro gradients. Temporal, but not nasal axons stop at a
      distinct zone in the gradient, which is covered with a certain surface density of
      substrate-bound ephrinA5. Within the temporal RGC population, all axons respond
      uniformly to the gradients tested. The position of the stop zone depends on the
      slope of the gradient with axons growing further into the gradient in shallow
      gradients than in steep gradients. However, axons stop at lower ephrinA5
      concentrations in shallow gradients than in steep gradients, indicating that the
      growth cone can adjust its sensitivity during the detection of a concentration
      gradient of ephrinA5.

PMID- 17557154
TI  - Chronic steroid administration does not suppress Plasmodium development and
      maturation.
AB  - The objective of this study was to investigate the influence of constant steroid
      uptake on the Plasmodium yoelii infection rate and parasite maturation. On the
      animal model, we examined the effect(s) of dexamethasone (Dx), the general drug
      used for self-treatment by Thai villagers. Ten female ICR mice were subjected to
      oral administration of 0.5 mg/kg Dx for 40 days, whereas other ten were given
      drinking water only before P. yoelii 17X (lethal) strain inoculation. Parasite
      infected erythrocytes were verified by Giemsa staining under light microscope.
      The differences of infectivity and maturation were evaluated by Student's t test.
      Parasitemia was detected in both groups on day 1 and increased until day 6 with
      similar infection rates. Significant lower numbers of ring, trophozoite, and
      schizont stages in the control group at the same time compared to Dx-treated mice
      were noted. The parasite maturation in infected Dx-treated mice appeared faster
      in comparison to the control. We conclude that the chronic taking of Dx
      suppresses the host immunity, without any suppressive effects on the parasite
      development and maturation, and, on the contrary, increases the development and
      maturation of P. yoelii.

PMID- 17557155
TI  - Two new Eimeria species (Protozoa: Eimeriidae) from wild rock ptarmigans, Lagopus
      muta islandorum, in Iceland.
AB  - One hundred rock ptarmigans, Lagopus muta islandorum (Faber, 1822), were
      collected in early October 2006 in northeastern Iceland and examined for
      coccidian parasites. Two Eimeria species were identified, and each is described
      as a new species. Sporulated oocysts of one species are ellipsoidal, 24.9 x 16.6
      (19.5-30 x 14.5-19) microm. Oocysts have a small micropyle and a two-layered,
      smooth wall approximately 1.0 microm thick. An oocyst residuum is absent, but one
      to three polar granules are present. Sporocysts have a rounded end opposite a
      nipple-like Stieda body and are 14.3 x 6.3 (12-16.5 x 5.5-7) microm. Sporocysts
      contain one refractile body and a diffuse granular residuum; the entire contents
      of each sporocyst is enclosed by a thin membrane. Sporulated oocysts of the
      second eimerian are subspherical, 24.7 x 22.2 (20-28 x 18-24.5) microm. The
      oocysts are without a micropyle but with a two-layered wall, which is
      approximately 1.5 microm thick, with the outer layer having a rough surface
      texture. Oocyst residuum is absent, but one to two polar granules are present.
      Sporocysts have a rounded end opposite the nipple-like Stieda body atop a
      prominent sub-Stieda body and are 14.4 x 8.0 (12-15.5 x 6.5-9) microm. Sporocysts
      contain a diffuse granular residuum, and each sporozoite has two different-sized
      refractile bodies.

PMID- 17557156
TI  - Ultrastructural changes induced in the tegument and gut of Fasciola hepatica
      following in vivo and in vitro drug treatment with nitroxynil (Trodax).
AB  - Male Sprague-Dawley rats were dosed orally with nitroxynil at a concentration of
      40 mg/kg, and adult Fasciola hepatica were recovered after 24, 48 and 72 h. Fine
      structural changes to the tegument and gut were monitored by transmission
      electron microscopy. Flukes were also incubated for 24 h in vitro in nitroxynil
      at a concentration of 100 microg/ml. Following treatment in vivo, there was an
      accumulation and accelerated release of secretory bodies at the apex of the
      tegumental syncytium. Some swelling of the mucopolysaccharide masses surrounding
      the basal infolds was evident after 48 and 72 h. There was an initial
      accumulation of T1 secretory bodies at the base of the syncytium, but this
      decreased at 72 h, coinciding with a decline in their production in the
      tegumental cells. The mitochondria were consistently swollen in the tegumental
      cells. At 72 h, large vacuolations were observed between the muscle layers and
      there was flooding around the underlying tissues. Some tegumental cells were seen
      to be degenerating and beginning to disintegrate. After 24 h treatment in vitro,
      the basal infolds were swollen and the crystalline structure of the spines was
      disrupted. Flooding of the internal tissues was evident and, in the tegumental
      cells, Golgi complexes and secretory bodies were absent. The mitochondria in the
      tegumental cells were swollen. In the gastrodermal cells, changes were evident at
      the earliest time period in vivo. The lamellae were disrupted, few secretory
      bodies were present, the mitochondria and cisternae of granular endoplasmic
      reticulum (ger) were swollen and there was an increased number of secretory
      bodies. These changes became progressively more severe with time. Similar changes
      were evident following treatment in vitro; vesiculation of the ger was also seen.
      The results indicate that oral uptake is the predominant route of entry of
      nitroxynil into the fluke.

PMID- 17557157
TI  - Seasonal changes of immunocompetence and parasitism in chub (Leuciscus cephalus),
      a freshwater cyprinid fish.
AB  - Seasonal variation of water characteristics, predominantly temperature, is
      considered to strongly affect fish physiology and immunology. In nature, this
      variation directly influences the life cycle especially in fish parasites, but
      the infection of parasites is also altered by the host immune response. This
      study is aimed to analyze the seasonal changes in selected physiological and
      immunological parameters, the latter a potential measure of fish
      immunocompetence. Moreover, the seasonal changes in metazoan parasite infection
      were investigated, and the potential associations between fish physiology,
      immunocompetence, and parasitism were estimated. No differences in gender were
      recognized for immunological parameters. The significant differences in the
      spleen-somatic index were found among fish samples of different seasons
      indicating higher investment in spleen size in April (after winterizing) and
      August (post-breeding with low gonado-somatic index [GSI]). The significant
      seasonal differences in erythrocyte and leukocyte cell counts, as well as in
      phagocyte count affecting respiratory burst, were recorded. The general trend of
      leukocyte composition was similar in all seasons investigated; however, the
      changes in proportion of different neutrophilic cells were reported. The parasite
      diversity and the infection parameters in parasite communities were highest in
      spring and early summer. When comparing parasite abundance in infracommunities
      among seasons, the statistically highest values were observed in April and June
      for Monogenea, in April and November for Acanthocephala, and in April for
      Cestoda. The positive correlations between GSI and the parasite abundance of
      groups with higher infection parameters were found in males. Moreover, the
      positive association between Monogenea as the dominant parasite group and
      respiratory burst was observed. The higher investment in condition and the
      seasonal variation in GSI were associated with a decrease immune function
      measured by spleen size or leukocyte cell count especially for males suggesting
      the seasonal energy allocation between immune function and somatic or
      reproductive investment.

PMID- 17557158
TI  - The COL1A1 gene and high myopia susceptibility in Japanese.
AB  - The collagen type Iota alpha Iota (COL1A1) gene encodes the extracellular matrix
      component, collagen, and resides in candidate MYP5 for high myopia on the
      chromosome 17q22-q23.3. This locus has recently been implicated in playing an
      important role in the pathogenesis of experimental myopia. We investigated the
      association of disruptions of COL1A1 gene with high myopia by analyzing the
      frequency of ten SNPs in a Japanese population of 330 subjects with high myopia
      of -9.25 D or less and 330 randomized controls without high myopia. Two SNPs
      (rs2075555 and rs2269336) were significantly associated with high myopia (P <
      0.05, Pc < 0.1). Two different haplotype blocks in COL1A1 were observed by the
      pair-wise linkage disequilibrium between the SNPs. The frequency of GGC/GGC
      diplotype constructed by the three SNPs (rs2075555, rs2269336, rs1107946) was
      significantly high (OR = 1.6) and associated with high myopia (P = 0.028, Pc<
      0.084). Together our results provide the first evidence for COL1A1 as a gene
      associated with high myopia.

PMID- 17557164
TI  - Inhibition of the activity of human lymphocyte Kv1.3 potassium channels by
      resveratrol.
AB  - The whole-cell patch-clamp technique was applied to study the modulatory effect
      of resveratrol on voltage-gated potassium channel Kv1.3 expressed in human
      lymphocytes. Results demonstrate that application of resveratrol in the
      concentration range 1-200 muM: inhibited the channel activity in a concentration
      dependent manner to about 18% of the control value. The half-blocking
      concentration of resveratrol was 40.9 microM: , whereas the Hill coefficient was
      1.05. The inhibition was time-dependent and slowly reversible. The inhibitory
      effect of resveratrol was correlated in time with a significant slowing of the
      current activation, whereas the inactivation rate remained unaffected upon
      application of resveratrol. The inhibition of Kv1.3 channels was voltage
      independent. The steady-state activation of the currents remained unchanged upon
      resveratrol application. The magnitude of the inhibitory effect of resveratrol
      was not altered when resveratrol was coapplied with genistein. The possible
      mechanism of the inhibitory effect and its significance for biological activity
      of resveratrol are discussed.

PMID- 17557165
TI  - The power of two-dimensional dwell-time analysis for model discrimination,
      temporal resolution, multichannel analysis and level detection.
AB  - Two-dimensional (2D) dwell-time analysis of time series of single-channel patch
      clamp current was improved by employing a Hinkley detector for jump detection,
      introducing a genetic fit algorithm, replacing maximum likelihood by a least
      square criterion, averaging over a field of 9 or 25 bins in the 2D plane and
      normalizing per measuring time, not per events. Using simulated time series for
      the generation of the "theoretical" 2D histograms from assumed Markov models
      enabled the incorporation of the measured filter response and noise. The effects
      of these improvements were tested with respect to the temporal resolution,
      accuracy of the determination of the rate constants of the Markov model,
      sensitivity to noise and requirement of open time and length of the time series.
      The 2D fit was better than the classical hidden Markov model (HMM) fit in all
      tested fields. The temporal resolution of the two most efficient algorithms, the
      2D fit and the subsequent HMM/beta fit, enabled the determination of rate
      constants 10 times faster than the corner frequency of the low-pass filter. The
      2D fit was much less sensitive to noise. The requirement of computing time is a
      problem of the 2D fit (100 times that of the HMM fit) but can now be handled by
      personal computers. The studies revealed a fringe benefit of 2D analysis: it can
      reveal the "true" single-channel current when the filter has reduced the apparent
      current level by averaging over undetected fast gating.

PMID- 17557166
TI  - Association of renal Na,K-ATPase alpha-subunit with the beta- and gamma-subunits
      based on cryoelectron microscopy.
AB  - Na,K-ATPase transports Na(+) and K(+) across cell membranes and consists of alpha
      and beta-subunits. Na,K-ATPase also associates with small FXYD proteins that
      regulate the activity of the pump. We have used cryoelectron microscopy of two
      dimensional crystals including data to 8 A resolution to determine the three
      dimensional (3-D) structure of renal Na,K-ATPase containing FXYD2, the gamma
      subunit. A homology model for the alpha-subunit was calculated from a Ca(2+)
      ATPase structure and used to locate the additional beta- and gamma-subunits
      present in the 3-D map of Na,K-ATPase. Based on the 3-D map, the beta-subunit is
      located close to transmembrane helices M8 and M10 and the gamma-subunit is
      adjacent to helices M2 and M9 of the alpha-subunit.

PMID- 17557167
TI  - How common are intragene windows with KA > KS owing to purifying selection on
      synonymous mutations?
AB  - One method for diagnosing the mode of sequence evolution considers the ratio of
      nonsynonymous substitutions per nonsynonymous site (K (A)) to the corresponding
      figure for synonymous substitutions (K (S)). A ratio (K (A)/K (S)) greater than
      unity is taken as evidence for positive selection. This, however, need not
      necessarily be the case. Notably, there is one instance of a high intragenic K
      (A)/K (S) peak, revealed by sliding window analysis and observed in two pairwise
      comparisons, better accounted for by localised purifying selection on synonymous
      mutations that affect splicing. Is this example exceptional? To address this we
      isolate intragenic domains with K (A)/K (S) > 1 from more than 1000 long mouse
      rat orthologues. Approximately one K (A)/K (S) > 1 peak is found per 12-15 kb of
      coding sequence. Surprisingly, low synonymous substitution rates underpin more
      incidences than do high nonsynonymous rates. Several reasons, however, prevent us
      from supposing that the low synonymous rates reflect purifying selection on
      synonymous mutations. First, for many peaks, the null that the peak is no higher
      than expected given the underlying rates of evolution, cannot be rejected.
      Second, of 18 statistically significant incidences with unusually low K (S)
      values, only 3 are repeatable across independent comparisons. At least two of
      these are within alternatively spliced exons. We conclude that repeatable
      statistically significant intragenic domains of low intragenic K (S) are rare. As
      so few K (A)/K (S) peaks reflect increased rates of protein evolution and so few
      hold statistical support, we additionally conclude that sliding window analysis
      to infer domains of positive selection is highly error-prone.

PMID- 17557169
TI  - Changes in morphology and elemental composition of Vibrio splendidus along a
      gradient from carbon-limited to phosphate-limited growth.
AB  - We examined morphology, elemental composition (C, N, P), and orthophosphate
      uptake efficiency in the marine heterotrophic bacterium Vibrio splendidus grown
      in continuous cultures. Eight chemostats were arranged along a gradient of
      increasing glucose concentrations in the reservoirs, shifting the limiting factor
      from glucose to phosphate. The content of carbon, nitrogen, and phosphorus was
      measured in individual cells by x-ray microanalysis using a transmission electron
      microscope (TEM). Cell volumes (V) were estimated from length and width
      measurements of unfixed, air-dried cells in TEM. There was a transition from
      coccoid cells in C-limited cultures toward rod-shaped cells in P-limited
      cultures. Cells in P-limited cultures with free glucose in the media were
      significantly larger than cells in glucose-depleted cultures (P < 0.0001). We
      found functional allometry between cellular C-, N-, and P content (in femtograms)
      and V (in cubic micrometers) in V. splendidus (C = 224 x V(0.89), N = 52.5 x
      V(0.80), P = 2 x V(0.65)); i.e., larger bacteria had less elemental C, N, and P
      per V than smaller cells, and also less P relative to C. Biomass-specific
      affinity for orthophosphate uptake in large P-limited V. splendidus approached
      theoretical maxima predicted for uptake limited by molecular diffusion toward the
      cells. Comparing these theoretical values to respective values for the smaller,
      coccoid, C-limited V. splendidus indicated, contrary to the traditional view,
      that large size did not represent a trade-off when competing for the non-C
      limiting nutrients.

PMID- 17557168
TI  - Characterization of the cDNAs encoding three GnRH forms in the pejerrey fish
      Odontesthes bonariensis (Atheriniformes) and the evolution of GnRH precursors.
AB  - Most vertebrates express two gonadotropin releasing hormone (GnRH) variants in
      brain tissue but there is an increasing number of fish species for which a third
      GnRH form has been detected. We characterized the precursors (cDNAs) of all three
      forms expressed in the brain of the pejerrey (silverside) fish, Odontesthes
      bonariensis (Atheriniformes): type I (GnRH-I; 440 bp), type II (GnRH-II; 529 bp),
      and type III (GnRH-III; 515 bp). The expression of these GnRHs precursors was
      also observed in peripheral tissues related to reproduction (gonads), visual and
      chemical senses (eye and olfactory epithelium), and osmoregulation (gill),
      suggesting that in teleost fish and possibly other vertebrates GnRH mediates
      directly or indirectly many other functions besides reproduction. We also present
      a comprehensive phylogenetic analysis including representatives of all chordate
      GnRH precursors characterized to date that supports the idea of two main
      paralogous GnRH lineages with different function. A "forebrain lineage" separates
      evolutionarily from the "midbrain lineage" as a result of an ancient duplication
      (ca. 600 million years ago). A third, fish-only clade of GnRH genes seems to have
      originated before the divergence of fish and tetrapods but retained only in fish.
      Phylogenetic analyses of GnRH precursors (DNA and protein sequences) under
      different optimality criteria converge on this result. Although alternative
      scenarios could not be statistically rejected in this study due to the relatively
      short size of the analyzed molecules, this hypothesis also receives support from
      chromosomal studies of synteny around the GnRH genes in vertebrates.

PMID- 17557170
TI  - Impact of urban sprawl on water quality in eastern Massachusetts, USA.
AB  - A study of water quality, land use, and population variations over the past three
      decades was conducted in eastern Massachusetts to examine the impact of urban
      sprawl on water quality using geographic information system and statistical
      analyses. Since 1970, eastern Massachusetts has experienced pronounced urban
      sprawl, which has a substantial impact on water quality. High spatial
      correlations are found between water quality indicators (especially specific
      conductance, dissolved ions, including Ca, Mg, Na, and Cl, and dissolved solid)
      and urban sprawl indicators. Urbanized watersheds with high population density,
      high percentage of developed land use, and low per capita developed land use
      tended to have high concentrations of water pollutants. The impact of urban
      sprawl also shows clear spatial difference between suburban areas and central
      cities: The central cities experienced lower increases over time in specific
      conductance concentration, compared to suburban and rural areas. The impact of
      urban sprawl on water quality is attributed to the combined effects of population
      and land-use change. Per capita developed land use is a very important indicator
      for studying the impact of urban sprawl and improving land use and watershed
      management, because inclusion of this indicator can better explain the temporal
      and spatial variations of more water quality parameters than using individual
      land use or/and population density.

PMID- 17557171
TI  - Ecological success in stream restoration: case studies from the midwestern United
      States.
AB  - Despite rapid growth in river restoration, few projects receive the necessary
      evaluation and reporting to determine their success or failure and to learn from
      experience. As part of the National River Restoration Science Synthesis, we
      interviewed 39 project contacts from a database of 1,345 restoration projects in
      Michigan, Wisconsin, and Ohio to (1) verify project information; (2) gather data
      on project design, implementation, and coordination; (3) assess the extent of
      monitoring; and (4) evaluate success and the factors that may influence it.
      Projects were selected randomly within the four most common project goals from a
      national database: in-stream habitat improvement, channel reconfiguration,
      riparian management, and water-quality improvement. Roughly half of the projects
      were implemented as part of a watershed management plan and had some advisory
      group. Monitoring occurred in 79% of projects but often was minimal and seldom
      documented biological improvements. Baseline data for evaluation often relied on
      previous data obtained under regional monitoring programs using state protocols.
      Although 89% of project contacts reported success, only 11% of the projects were
      considered successful because of the response of a specific ecological indicator,
      and monitoring data were underused in project assessment. Estimates of ecological
      success, using three criteria from Palmer and others (2005), indicated that half
      or fewer of the projects were ecologically successful, markedly below the success
      level that project contacts self-reported, and sent a strong signal of the need
      for well-designed evaluation programs that can document ecological success.

PMID- 17557172
TI  - The contribution of environmental assessment to sustainable development: toward a
      richer empirical understanding.
AB  - It has long been suggested that environmental assessment has the potential to
      contribute to sustainable development through mechanisms above and beyond
      informing design and consent decisions, and while theories have been proposed to
      explain how this might occur, few have been subjected to rigorous empirical
      validation. This research advances the theoretical debate by building a rich
      empirical understanding of environmental assessment's practical outcomes, from
      which its potential to contribute to sustainable development can be gauged. Three
      case study environmental assessment processes in England were investigated using
      a combination of data generated from content analysis, in-depth interviews, and a
      questionnaire survey. Four categories of outcomes are delineated based on the
      research data: learning outcomes; governance outcomes; attitudinal and value
      changes; and developmental outcomes. The data provide a robust critique of
      mainstream theory, with its focus on design and consent decisions. The article
      concludes with an examination of the consequences of the context-specific nature
      of environmental assessment practices in terms of developing theory and focusing
      future research.

PMID- 17557173
TI  - Predicting the impacts of future sea-level rise on an endangered lagomorph.
AB  - Human-induced global climate change presents a unique and difficult challenge to
      the conservation of biodiversity. Despite increasing attention on global climate
      change, few studies have assessed the projected impacts of sea-level rise to
      threatened and endangered species. Therefore, we estimated the impacts of rising
      sea levels on the endangered Lower Keys marsh rabbit (Sylvilagus palustris
      hefneri) across its geographic distribution under scenarios of current
      conditions, low (0.3-m), medium (0.6-m), and high (0.9-m) sea-level rise. We also
      investigated the impacts of allowing vegetation to migrate upslope and not
      allowing migration and of two land-use planning decisions (protection and
      abandonment of human-dominated areas). Not surprisingly, under all simulations we
      found a general trend of decreasing total potential LKMR habitat with increasing
      sea-level rise. Not allowing migration and protecting human-dominated areas both
      tended to decrease potential LKMR habitat compared with allowing migration and
      abandoning human-dominated areas. In conclusion, conservation strategies at
      multiple scales need to be implemented in order to reduce the impact of global
      climate change on biodiversity and endangered species. At the regional level,
      managers must consider land-use planning needs that take into account the needs
      of both humans and biodiversity. Finally, at the local scale those agencies that
      are in charge of endangered species conservation and ecosystem management need to
      rethink static approaches to conservation or else stand by and watch ecosystems
      degrade and species go extinct. This can be accomplished by bioclimatic reserve
      systems where climatically underrepresented areas are included in conservation
      planning along with the standard concerns of threat, opportunity, connectivity,
      and viability.

PMID- 17557174
TI  - Assessment of stream ecosystem function and sensitivity in the Bighorn National
      Forest, Wyoming.
AB  - This paper presents a hierarchical analysis of stream ecosystem distribution and
      sensitivity to natural and anthropogenic disturbances for the Bighorn National
      Forest, Wyoming. We designated stream gradient, flow regime, and lithology as
      environmental parameters that would result in the most robust, readily applied,
      and parsimonious description of physical and chemical characteristics of
      individual stream segments. We used these parameters to map the spatial
      distribution and relative abundance of stream habitats in the study area. We then
      used the proportion of each sixth-level hydrologic unit boundary comprised by
      each category of stream gradient, flow regime, and lithology as input to an
      agglomerative cluster analysis, which identified six clusters for the 74
      watersheds intersecting or within the national forest boundary. Five of the six
      clusters have predominantly high gradient streams and runoff dominated by
      snowmelt or mixed snowmelt and rainfall. Most watersheds on the Bighorn National
      Forest are sensitive to alterations in water supply because of the relatively
      small size of streams. Although watersheds are generally less sensitive to
      changed sediment supply, low-gradient stream segments create sensitive sites
      within individual watersheds. Field verification studies indicate that this
      approach reasonably characterizes physical channel properties and biological
      associations for the study area.

PMID- 17557175
TI  - Influence of cutting time on brush response: implications for herbivory in linear
      (transportation) corridors.
AB  - An experiment was conducted to determine the influence the time of brush-cutting
      can have on plant regrowth and attractiveness to herbivores that browse in linear
      corridors. The influence of cutting time on leaf flush and senescence, shoot
      morphometry, and biomass was measured for 3 consecutive years after initial brush
      cutting. Results indicate that morphological and phenological attributes of three
      woody deciduous plants were influenced by the timing of brush-cutting for up to 3
      years after initial cutting. Brush-cutting generally stimulated plants to produce
      larger than normal shoots and delay leaf senescence. The degree to which plants
      were affected, however, varied with the timing of initial cutting and the species
      in question. Generally, plants cut later in the year resprouted more vigorously
      and were taller in the third year after cutting but produced less overall biomass
      than when cut earlier. In the years following brush-cutting, plants cut earlier
      flushed leaves earlier in the spring but delayed leaf senescence in the fall when
      compared to uncut controls. Results of these trials suggest that brush-cutting
      time influences plant response and several plant attributes known to influence
      plant attractiveness to moose and other herbivores. We therefore recommend that
      roadside and railside vegetation management plans consider the influence of
      cutting time on plant regrowth. Such considerations can ensure that brush is cut
      to reduce the attractiveness of plant regrowth in these linear corridors, reduce
      the utilization of such brush by herbivores, and, as such, mitigate collision
      risk between motorists and herbivores such as moose.

PMID- 17557177
TI  - Generation of rat mutants using a coat color-tagged Sleeping Beauty transposon
      system.
AB  - A significant barrier to exploiting the full potential of the rat as a biomedical
      model is the lack of tools to easily modify its germline. Here we show that a
      tyrosinase-tagged Sleeping Beauty transposon can be used as a simple, efficient
      method to generate rat mutants in vivo. By making two lines of transgenic rats,
      one carrying the transposon and another expressing the transposase in germ cells,
      we are able to obtain bigenic males in which transposition occurs in the germ
      cells. We show that transposition leads to the appearance of new coat colors in
      the offspring. Using such bigenic males, we obtained an average of 1.2
      transpositions per gamete and identified 19 intragenic integration events among
      96 transposition sites that were sequenced. In addition, gene trapping was
      confirmed and rats with evidence for transposon-induced dominant ocular anomalies
      were identified. These data suggest that the modified Sleeping Beauty transposon
      represents a powerful new tool for producing molecularly defined mutagenesis in
      the rat.

PMID- 17557176
TI  - Mammary tumor modifiers in BALB/cJ mice heterozygous for p53.
AB  - BALB/c mice are predisposed to developing spontaneous mammary tumors, which are
      further increased in a p53 heterozygous state. C57BL/6J mice are resistant to
      induced mammary tumors and develop less than 1% mammary tumors in both wild-type
      and p53+/- states. To map modifiers of mammary tumorigenesis, we have established
      F1 and F2 crosses and backcrosses to BALB/cJ (N2-BALB/cJ) and C57BL/6J (N2
      C57BL/6J) strains. All cohorts developed mammary carcinomas in p53+/- females,
      suggesting that multiple loci dominantly and recessively contributed to mammary
      tumorigenesis. We mapped two modifiers of mammary tumorigenesis in the BALB/cJ
      strain. Mtsm1 (mammary tumor susceptibility modifier), a dominant-acting
      modifier, is located on chromosome 7. Mtsm1 is suggestive for linkage to mammary
      tumorigenesis (p = 0.001). We have analyzed the Mtsm1 region to locate candidate
      genes by comparing it to a rat modifier region, Mcs3, which shares syntenic
      conservation with Mtsm1. Expression data and SNPs were also taken into account.
      Five potential candidate genes within Mtsm1 are Aldh1a3, Chd2, Nipa2, Pcsk6, and
      Tubgcp5. The second modifier mapped is Mtsm2, a recessive-acting modifier. Mtsm2
      is located on chromosome X and is significantly linked to mammary tumorigenesis
      (p = 1.03 x 10(-7)).

PMID- 17557178
TI  - Quantitative trait loci for peripheral blood cell counts: a study in baboons.
AB  - Increasingly, baseline peripheral blood cell counts are implicated as risk
      factors for common complex diseases. While genetic influences on these
      hematologic parameters are firmly established, the genetic architecture of the
      blood counts is still poorly understood. In this article we used data from 582
      healthy pedigreed baboons and variance components methods to localize
      quantitative trait loci (QTLs) influencing complete blood count variables.
      Besides performing genome-wide linkage scans for each trait individually, we
      conducted bivariate linkage analyses for all pairwise trait combinations to also
      identify pleiotropic QTLs influencing several blood counts. While significant and
      suggestive QTLs were localized throughout the genome (LOD range: 1.5-3.5),
      chromosomal regions associated with the expression of various hematologic
      parameters stand out. In particular, our results provide significant and
      consistent evidence for a QTL on the orthologous human chromosome 1p that is
      shared by several blood counts, mainly erythrocyte parameters. In addition,
      multiple suggestive evidence of linkage was detected on the orthologous human
      chromosomes 10 (near the q-terminus) and 19 (centromeric section). Future studies
      should help identify the genes responsible for these QTL and elucidate their role
      on baseline variation in hematologic indicators of health and disease.

PMID- 17557179
TI  - Genetic randomization reveals functional relationships among morphologic and
      tissue-quality traits that contribute to bone strength and fragility.
AB  - We examined femora from adult AXB/BXA recombinant inbred (RI) mouse strains to
      identify skeletal traits that are functionally related and to determine how
      functional interactions among these traits contribute to genetic variability in
      whole-bone stiffness, strength, and toughness. Randomization of A/J and C57BL/6J
      genomic regions resulted in each adult male and female RI strain building
      mechanically functional femora by assembling unique sets of morphologic and
      tissue-quality traits. A correlation analysis was conducted using the mean trait
      values for each RI strain. A third of the 66 correlations examined were
      significant, indicating that many bone traits covaried or were functionally
      related. Path analysis revealed important functional interactions among bone
      slenderness, cortical thickness, and tissue mineral density. The path
      coefficients describing these functional relations were similar for both sexes.
      The causal relationship among these three traits suggested that cellular
      processes during growth simultaneously regulate bone slenderness, cortical
      thickness, and tissue mineral density so that the combination of traits is
      sufficiently stiff and strong to satisfy daily loading demands. A disadvantage of
      these functional interactions was that increases in tissue mineral density also
      deleteriously affected tissue ductility. Consequently, slender bones with high
      mineral density may be stiff and strong but they are also brittle. Thus,
      genetically randomized mouse strains revealed a basic biological paradigm that
      allows for flexibility in building bones that are functional for daily activities
      but that creates preferred sets of traits under extreme loading conditions.
      Genetic or environmental perturbations that alter these functional interactions
      during growth would be expected to lead to loss of function and suboptimal adult
      bone quality.

PMID- 17557182
TI  - Clinical potential of digital linear tomosynthesis imaging of total joint
      arthroplasty.
AB  - The present study was performed to evaluate the potential for clinical
      application of digital linear tomosynthesis in imaging hip prostheses. Volumetric
      x-ray digital linear tomosysnthesis was used to image hip prostheses. The
      tomosynthesis was compared to metal artifact reduction (MAR) computed tomography
      (CT), and non-MAR CT scans of a prosthesis case. The effectiveness of this method
      in enhancing visibility of a prosthesis case was quantified in terms of the
      signal-to-noise ratio (SNR), and removal of ghosting artifacts in a prosthesis
      case was quantified in terms of the artifact spread function (ASF). In the near
      in-focus plane, the contrast is greater in the MAR CT or tomosynthesis relative
      to the non-MAR CT. The order of ASF performance of the algorithm was as follows:
      (1) tomosynthesis; (2) MAR-CT; (3) non-MAR CT. The potential usefulness of
      digital linear tomosynthesis for evaluation of hip prostheses was demonstrated.
      Further studies are required to determine the ability of digital linear
      tomosynthesis to quantify the spatial relationships between the metallic
      components of these devices as well as to identify bony changes with diagnostic
      consequences.

PMID- 17557180
TI  - Comparative genomics reveals functional transcriptional control sequences in the
      Prop1 gene.
AB  - Mutations in PROP1 are a common genetic cause of multiple pituitary hormone
      deficiency (MPHD). We used a comparative genomics approach to predict the
      transcriptional regulatory domains of Prop1 and tested them in cell culture and
      mice. A BAC transgene containing Prop1 completely rescues the Prop1 mutant
      phenotype, demonstrating that the regulatory elements necessary for proper PROP1
      transcription are contained within the BAC. We generated DNA sequences from the
      PROP1 genes in lemur, pig, and five different primate species. Comparison of
      these with available human and mouse PROP1 sequences identified three putative
      regulatory sequences that are highly conserved. These are located in the PROP1
      promoter proximal region, within the first intron of PROP1, and downstream of
      PROP1. Each of the conserved elements elicited orientation-specific enhancer
      activity in the context of the Drosophila alcohol dehydrogenase minimal promoter
      in both heterologous and pituitary-derived cells lines. The intronic element is
      sufficient to confer dorsal expansion of the pituitary expression domain of a
      transgene, suggesting that this element is important for the normal spatial
      expression of endogenous Prop1 during pituitary development. This study
      illustrates the usefulness of a comparative genomics approach in the
      identification of regulatory elements that may be the site of mutations
      responsible for some cases of MPHD.

PMID- 17557183
TI  - Reconstruction of some hybrid phylogenetic networks with homoplasies from
      distances.
AB  - Suppose G is a phylogenetic network given as a rooted acyclic directed graph. Let
      X be a subset of the vertex set containing the root, all leaves, and all vertices
      of outdegree 1. A vertex is "regular" if it has a unique parent, and "hybrid" if
      it has two parents. Consider the case where each gene is binary. Assume an
      idealized system of inheritance in which no homoplasies occur at regular
      vertices, but homoplasies can occur at hybrid vertices. Under our model, the
      distances between taxa are shown to be described using a system of numbers called
      "originating weights" and "homoplasy weights." Assume that the distances are
      known between all members of X. Sufficient conditions are given such that the
      graph G and all the originating and homoplasy weights can be reconstructed from
      the given distances.

PMID- 17557184
TI  - On a nonautonomous SEIRS model in epidemiology.
AB  - In this paper, we derive some threshold conditions for permanence and extinction
      of diseases that can be described by a nonautonomous SEIRS epidemic model. Under
      the quite weak assumptions, we establish some sufficient conditions to prove the
      permanence and extinction of disease. Some new threshold values are determined.

PMID- 17557185
TI  - Turing pattern formation with two kinds of cells and a diffusive chemical.
AB  - We study a three-variable Turing system with two kinds of cells and a diffusive
      chemical, considering the formation and maintenance of fish skin patterns with
      multiple pigment cells. The two types of cells are produced from undifferentiated
      cells. They inhibit the supply rate of the other cell type, forming local
      clusters of the same cell type. In addition, the cells of one type can be
      maintained only in the presence of a diffusive chemical produced by the other
      cell type, resulting in the coexistence of two cell types in heterogeneous
      spatial patterns. We assume linear interaction among cells and the chemical, and
      cell supply rates constrained to be positive or zero. We derive the condition for
      diffusion-driven instability. In one-dimensional model, we examine how the
      wavelength of the periodic pattern depends on parameters. In the two-dimensional
      model, we study the condition for spot, stripe or reversed spot pattern to emerge
      (pattern selection). We discuss heuristic criteria for the pattern selection.

PMID- 17557186
TI  - Practical identifiability of HIV dynamics models.
AB  - We study the practical identifiability of parameters, i.e., the accuracy of the
      estimation that can be hoped, in a model of HIV dynamics based on a system of non
      linear Ordinary Differential Equations (ODE). This depends on the available
      information such as the schedule of the measurements, the observed components,
      and the measurement precision. The number of patients is another way to increase
      it by introducing an appropriate statistical "population" framework. The impact
      of each improvement of the experimental condition is not known in advance but it
      can be evaluated via the Fisher Information Matrix (FIM). If the non-linearity of
      the biological model, as well as the complex statistical framework makes
      computation of the FIM challenging, we show that the particular structure of
      these models enables to compute it as precisely as wanted. In the HIV model,
      measuring HIV viral load and total CD4+ count were not enough to achieve
      identifiability of all the parameters involved. However, we show that an
      appropriate statistical approach together with the availability of additional
      markers such as infected cells or activated cells should considerably improve the
      identifiability and thus the usefulness of dynamical models of HIV.

PMID- 17557187
TI  - To cut or not to cut: a modeling approach for assessing the role of male
      circumcision in HIV control.
AB  - A recent randomized controlled trial shows a significant reduction in women-to
      men transmission of HIV due to male circumcision. Such development calls for a
      rigorous mathematical study to ascertain the full impact of male circumcision in
      reducing HIV burden, especially in resource-poor nations where access to anti
      retroviral drugs is limited. First of all, this paper presents a compartmental
      model for the transmission dynamics of HIV in a community where male circumcision
      is practiced. In addition to having a disease-free equilibrium, which is locally
      asymptotically stable whenever a certain epidemiological threshold is less than
      unity, the model exhibits the phenomenon of backward bifurcation, where the
      disease-free equilibrium coexists with a stable endemic equilibrium when the
      threshold is less than unity. The implication of this result is that HIV may
      persist in the population even when the reproduction threshold is less than
      unity. Using partial data from South Africa, the study shows that male
      circumcision at 60% efficacy level can prevent up to 220,000 cases and 8,200
      deaths in the country within a year. Further, it is shown that male circumcision
      can significantly reduce, but not eliminate, HIV burden in a community. However,
      disease elimination is feasible if male circumcision is combined with other
      interventions such as ARVs and condom use. It is shown that the combined use of
      male circumcision and ARVs is more effective in reducing disease burden than the
      combined use of male circumcision and condoms for a moderate condom compliance
      rate.

PMID- 17557188
TI  - Density dependent behavior at habitat boundaries and the Allee effect.
AB  - Habitat edges can have a number of effects on populations, including modifying
      their patterns of dispersal. Dispersal patterns can influence population
      dynamics. In this paper, we explore the possible effects of a pattern of
      dispersal where the response of organisms to the boundary of a habitat patch
      depends on their local density. We model a population of organisms diffusing and
      growing logistically inside a patch, but with the likelihood of an individual
      crossing the patch boundary to leave the patch decreasing as the local density of
      conspecifics within the patch increases. Such behavior at patch boundaries has
      been observed among Glanville fritillary butterflies, and has been proposed as a
      mechanism for generating an Allee effect at the patch level. Our models predict
      that the behavior can indeed induce an Allee effect at the patch level even
      though there is no such effect built into the local population dynamics inside
      the patch. The models are relatively simple and are not intended to give a
      complete description of any particular population, but only to verify the idea
      that the mechanism of density-dependent dispersal behavior at a patch boundary is
      capable of altering population dynamics within the patch.

PMID- 17557189
TI  - Long-term retention of smoking cessation counseling skills learned in the first
      year of medical school.
AB  - BACKGROUND: Tobacco use is a significant cause of preventable morbidity and
      mortality in the United States, yet clinicians underutilize smoking cessation
      counseling. Medical schools are increasingly including training for smoking
      cessation skills in preclinical curricula. Information about long-term retention
      of these skills is needed. OBJECTIVE: To assess retention of smoking cessation
      counseling skills learned in the first year of medical school. DESIGN:
      Retrospective review of data collected for routine student and curriculum
      assessment. PARTICIPANTS: Two cohorts of medical students at the University of
      Connecticut School of Medicine (total N = 112) in 1999-2001 and 2002-2004.
      MEASUREMENTS AND MAIN RESULTS: Scores by standardized patients were compared from
      first and fourth-year assessments, based on checklist items corresponding to the
      5 strategies recommended by the U.S. Public Health Service (Ask, Advise, Assess,
      Assist, Arrange). In study cases, 97% of first-year students "asked" about
      smoking and retained this skill in fourth year (p = .08). Ninety-four percent of
      first-year students "assessed" readiness to quit and retained this skill (p =
      .21). Ninety-six percent of first-year students "advised" smokers to quit and
      retained this skill (p = .18). Eighty-six percent of first year students
      "assisted" smokers in quitting and retained this skill (p = 0.10). Eighty-one
      percent of first year students "arranged" follow-up contact and performance of
      this strategy improved in the fourth year to 91% (p = .03). CONCLUSIONS: Smoking
      cessation counseling skills demonstrated by first year medical students were,
      with brief formal reinforcement in the third year, well retained into the fourth
      year of medical school. It is appropriate to begin this training early in medical
      education.

PMID- 17557190
TI  - Clinical oversight: conceptualizing the relationship between supervision and
      safety.
AB  - BACKGROUND: Concern about the link between clinical supervision and safe, quality
      health care has led to widespread increases in the supervision of medical
      trainees. The effects of increased supervision on patient care and trainee
      education are not known, primarily because the current multifacted and poorly
      operationalized concept of clinical supervision limits the potential for
      evaluation. OBJECTIVE: To develop a conceptual model of clinical supervision to
      inform and guide policy and research. DESIGN, SETTING, AND PARTICIPANTS:
      Observational fieldwork and interviews were conducted in the Emergency Department
      and General Internal Medicine in-patient teaching wards of two academic health
      sciences centers associated with an urban Canadian medical school. Members of 12
      Internal Medicine and Emergency Medicine teaching teams (n = 88) were observed
      during regular clinical activities (216 hours). Sixty-five participants (12
      physicians, 28 residents, 17 medical students, 8 nurses) also completed
      interviews about supervision. Field notes and interview transcripts were analyzed
      for emergent themes using grounded theory methodology. RESULTS: The term
      "clinical oversight" was developed to describe patient care activities performed
      by supervisors to ensure quality of care. "Routine oversight" (preplanned
      monitoring of trainees' clinical work) can expose supervisors to concerns that
      trigger "responsive oversight" (a double-check or elaboration of trainees'
      clinical work). Supervisors sometimes engage in "backstage oversight" (oversight
      of which the trainee is not directly aware). When supervisors encounter a
      situation that exceeds a trainee's competence, they move beyond clinical
      oversight to "direct patient care". CONCLUSIONS: This study elaborates a typology
      of clinical oversight activities including routine, responsive, and backstage
      oversight. This new typology provides a framework for clinical supervision policy
      and for research to evaluate the relationship between supervision and safety.

PMID- 17557191
TI  - Two specific inhibitors of the phosphatidylinositol 3-kinase LY294002 and
      wortmannin up-regulate beta1,4-galactosyltransferase I and thus sensitize SMMC
      7721 human hepatocarcinoma cells to cycloheximide-induced apoptosis.
AB  - Previous study indicated that beta1,4-galactosyltransferase I (beta1,4GT1) was up
      regulated by cycloheximide (CHX) and thus enhanced apoptosis induced by CHX in
      SMMC-7721 cells. In this study, we reported that constitutively active Akt
      protein (myr-Akt) inhibited CHX-induced apoptosis in SMMC-7721 cells through down
      regulating beta1,4GT1. However, the two PI3K inhibitors LY294002 and wortmannin
      treatment up-regulated beta1,4GT1 through enhancing Sp1 protein expression and
      consequently increased CHX-induced SMMC-7721 cells apoptosis. Besides, our
      results suggested that beta1,4GT1 and cell surface galactose residues synthesized
      by elevated beta1,4GT1 played an important role in SMMC-7721 cells apoptosis
      treated with CHX and PI3K inhibitor together. Moreover, we found that CHX
      accentuated beta1,4GT1 through down-regulating Akt expression to mediate SMMC
      7721 cells apoptosis. Taken together, PI3K inhibitors LY294002 and wortmannin up
      regulated beta1,4GT1 and enhanced CHX-induced apoptosis in SMMC-7721 cells, which
      suggested that PI3K inhibitors might have therapeutic potential when combined
      with CHX in the treatment of hepatoma.

PMID- 17557192
TI  - cAMP regulates vegetative growth and cell cycle in Candida albicans.
AB  - We demonstrate here the regulatory role of cAMP in cell cycle of Candida
      albicans. cAMP was found to be a positive signal for growth and morphogenesis.
      Phosphodiesterase inhibitor aminophylline exhibited significant effects, i.e.,
      increased growth, as well as induced morphogenesis. Atropine and trifluoperazine
      negatively regulated (inhibited) growth and did not induce morphogenesis. These
      changes were attributed to increase in cAMP levels and protein kinase A (PKA)
      activity in presence of aminophylline, while reduction was observed in atropine
      and trifluoperazine (TFP) grown cells. Alteration in cAMP signaling pathway
      affected the cell cycle progression in Candida albicans. Increased cAMP levels in
      aminophylline grown cells reduced the duration of cell cycle by inciting the cell
      cycle-specific expression of G1 cyclins (CLN1 and CLN2). However atropine and
      trifluoperazine delayed the expression of G1 cyclins and hence prolonged the cell
      cycle. Implication of cAMP signaling pathway in both the cell cycle and
      morphogenesis further opened the channels to explore the potential of this
      pathway to serve as a target for development of new antifungal drugs.

PMID- 17557193
TI  - NTPDase and 5'-nucleotidase activities in platelets of human pregnants with a
      normal or high risk for thrombosis.
AB  - The nucleotide degrading enzymes, ectonucleotidases, present on the platelet
      surface of human pregnant with a normal (without complications) or high risk for
      thrombosis (hypertension and gestational diabetes) were studied. NTPDase (E.C.
      3.6.1.5, CD39) and 5'-nucleotidase (E.C. 3.1.3.5, CD73) activities of four
      patient groups, non-pregnant (NP, n = 18), pregnant without complications (P, n =
      25), pregnant with hypertension (HP, n = 15) and pregnant with gestational
      diabetes mellitus (GDP, n = 10), were analyzed. Increased NTPDase activities were
      observed in the groups P (37.0%, S.D. = 2.03 and 34.0%, S.D. = 3.19), HP (40.0%,
      S.D. = 3.32 and 56.0%, S.D. = 3.25) and GDP (23.0%, S.D. = 2.30 and 42.0%, S.D. =
      2.26) in comparison to the control group NP (p < 0.01, S.D. = 1.92 and S.D. =
      2.48) when ATP and ADP were used as substrate, respectively. AMP was used as
      substrate to determine the 5'-nucleotidase activities, which showed to be
      elevated in the groups P (45.0%, S.D. = 1.73), HP (54.0%, S.D. = 2.64) and GDP
      (68.0%, S.D. = 1.69) when compared to the control group NP (p < 0.01, S.D. =
      1.26). However, no statistically significant differences were observed between
      the groups P, HP and GDP. As a consequence, the enhanced ATP, ADP and AMP
      hydrolysis was ascribed to the pregnancy itself, independent of a normal or high
      risk for thrombosis. The enhanced NTPDase and 5'-nucleotidase activities in
      platelets suggest that these enzymes are involved in the thromboregulation
      process in the pregnancy.

PMID- 17557194
TI  - Effect of exogenous melatonin on viability, ingestion capacity, and free-radical
      scavenging in heterophils from young and old ringdoves (Streptopelia risoria).
AB  - The decrease of melatonin production with aging contributes to the decline in
      immune function as organisms age. Treatment with the exogenously administered
      indoleamine restores the reduced immunological functions. Therefore, we
      investigated the effect of melatonin on viability, phagocyte ingestion capacity,
      and free radical generation levels of heterophils from young and old ringdove
      (Streptopelia risoria) aged 3-4 and 11-13 years, respectively. Animals received a
      single oral dose of melatonin 1 h before lights off for three consecutive days.
      Experiments were performed at the acrophases and nadirs of melatonin. Melatonin
      treatment significantly increased serum melatonin levels at the acrophases, but
      not at the nadirs of the two age groups. In both young and old animals there was
      increased heterophil viability at acrophases with respect to nadirs, and also
      increased cell resistance to oxidative stress in the old animals after the
      melatonin treatment. At acrophases, the index, percentage and efficiency of
      phagocytosis all increased significantly, and superoxide anion levels decreased
      significantly with respect to the nadir values of vehicle and melatonin-treated
      animals, the effect being greater in young than in old ringdoves. At the nadirs,
      no change was observed in any parameter analyzed. In both young and old animals,
      phagocytosis and melatonin were positively correlated, while superoxide anion
      levels and melatonin were negatively correlated. In conclusion, exogenous
      melatonin enhanced heterophil viability in old animals as well as increasing
      phagocytosis and free-radical scavenging in both age groups during the nocturnal
      period, accompanied by an increase in the levels of the indoleamine.

PMID- 17557196
TI  - New fluorescent antitumour cisplatin analogue complexes. Study of the
      characteristics of their binding to DNA by flow injection analysis.
AB  - The flow injection technique is applied to study the binding to DNA of new
      platinum complexes-E(1): ethylenediaminechlorocholylglycinateplatinum(II):
      [PtCl(CG)(en)], C(54)H(92)O(12)Pt and E(2):
      ethylenediaminebischolylglycinateplatinum(II): [Pt(CG)(2)(en)],
      C(28)H(50)ClN(3)O(6)Pt-derived from cisplatin in which the exchangeable ligands
      were replaced by bile acids, such that these anticancer drugs have less toxicity
      and less resistance is developed towards them. Both compounds are fluorescent and
      their fluorescence is enhanced when they form adducts with DNA, a property that
      is extremely useful for monitoring the cytotoxic activity and their mechanisms of
      action. The binding parameters to DNA of E(1) [apparent intrinsic binding
      constant K(E1): (11.2 +/- 0.4) x 10(3) M(-1) and maximum number of binding sites
      per nucleotide, n (E1): 0.121 +/- 2 x 10(-3)) and E(2) (K(E2): 9.2 +/- 0.7) x
      10(3) M(-1) and n (E2) 0.098 +/- 2 x 10(-3)] were determined following the
      Scatchard method and the type of binding was studied experimentally through the
      modifications introduced by each of the compounds into the ethidium bromide-DNA
      bond.

PMID- 17557195
TI  - Cell motility and cytoskeletal regulation in invasion and metastasis.
AB  - Cell motility and chemotaxis can make important contributions to the metastatic
      cascade. Cell migration pathways in general play significant roles in a variety
      of physiological processes that can be "hijacked" by cancer cells. Both growth
      factors and chemokines provide important chemotactic signals in development and
      metastasis. Receptor activation, following binding of a growth factor or a
      chemokine, leads to dynamic morphological changes in the actin cytoskeleton
      network via a variety of distinct and interconnected pathways, resulting in
      translocation of the cell up a chemoattractant gradient. Such gradients may be
      produced by stromal cells in the local microenvironment, including macrophages
      and fibroblasts. A better understanding of the mechanisms of cell motility and
      cytoskeletal regulation may provide novel therapeutic strategies that would block
      metastatic progression, reducing dissemination of tumor cells and increasing
      patient survival.

PMID- 17557197
TI  - A Fe(3+)/Hg (2+)-selective anthracene-based fluorescent PET sensor with
      tridentate ionophore of amide/beta-amino alcohol.
AB  - A new anthracene-based fluorescent PET sensor 1 with a tridentate ionophore of
      amide/beta-amino alcohol displays very good selectivity and sensitivity for
      Fe(3+) (K (a) = 1.6 x 10(3) M(-1)) and Hg(2+) (K (a) = 2.1 x 10(3) M(-1)) in
      CH(3)CN-H(2)O (3:7, v/v) with detection limit of 1 microM. More fluorescence
      enhancement was observed when 1 selectively detected Fe(3+) or Hg(2+) in CH(3)CN
      and its detection limit was up to 0.03 microM.

PMID- 17557198
TI  - The financial implications of availability and quality of a usual source of care
      for children with special health care needs.
AB  - OBJECTIVE: To examine the relationship of availability and quality of a usual
      source of care (USC) to medical expenditures overall and for various types of
      health care services for children with special health care needs (CSHCN), as a
      group and by four diagnostic subgroups (asthma, non-asthmatic physical
      conditions, mental retardation, other mental illnesses). METHODS: Generalized
      linear models were used to estimate the annual average per capita medical
      expenditures (APCME) based on data from 820 CSHCN in the 1995 National Health
      Interview Survey on Disability and 1996 Medical Expenditure Panel Survey.
      RESULTS: In 1996, 92% of non-institutionalized CSHCN in the United States had a
      USC. Of these, 52% were classified as receiving accessible care, 95% received
      comprehensive care, and 69% received satisfactory care. Approximately 89% of
      CSHCN had expenditures on health care in 1996 and the APCME was $1,344 for CSHCN
      as a group. Having a USC was associated with higher expenditures overall and for
      almost all types of health care services for CSHCN across conditions. Receiving
      comprehensive care was associated with lower total medical expenditures for CSHCN
      with asthma, whereas receiving satisfactory care was associated with higher total
      medical expenditures for CSHCN with non-asthma physical conditions. CONCLUSION:
      Having a regular care provider is associated with higher expenditures for CSHCN
      across diagnosis. Among CSHCN with a USC, quality of care is associated with
      medical expenditures, although specific associations vary by the quality
      characteristic and the condition of the child. These results may mask
      heterogeneity in severity of condition and quality of care over time.

PMID- 17557199
TI  - Salivary cotinine, doctor-diagnosed asthma and respiratory symptoms in primary
      schoolchildren.
AB  - Due to impaired airway function, children are at risk for adverse respiratory
      symptoms if exposed to environmental tobacco smoke (ETS). A community-based,
      cross-sectional study of 425 children (5-11 years) attending 15 primary schools
      in a low socio-economic area of Merseyside/UK was undertaken to investigate the
      association of adverse respiratory symptoms and ETS exposure using a parent
      completed questionnaire and children's salivary cotinine measurements. Overall,
      28.9% of children had doctor-diagnosed asthma (DDA) and 11.3% a history of
      hospital admission for respiratory illnesses. The symptom triad of cough, wheeze
      and breathlessness (C+W+B+) occurred in 12.6% of children. The geometric mean
      cotinine level was 0.37 ng/ml (95% CI, 0.33-0.42 ng/ml) and it was estimated that
      45.6% of children were ETS exposed. A history of asthma in the family was
      reported for 9.2% of fathers and 7.2% of mothers. Salivary cotinine level was
      significantly increased in children with DDA compared to those without (P =
      0.002). Cotinine-validated levels [adjusted odds ratio (AOR), 1.8; 95% CI, 1.4
      2.5), low socio-economic (disadvantaged) status (AOR, 1.4; 1.1-2.9), child's male
      gender (AOR, 1.6; 1.1-2.5) and maternal smoking (AOR, 2.2; 1.4-3.1) were
      significantly associated with DDA. The cotinine-validated level (AOR, 1.4; 1.1
      2.9) as well as maternal smoking (AOR, 1.8; 1.1-2.5), were also independently
      associated with C+W+B+. The use of salivary cotinine as an indicator of ETS
      exposure could be used to inform parents of exposure risk to their asthmatic
      children and may help re-enforce deterrent efforts to reduce childhood parental
      smoking exposure.

PMID- 17557200
TI  - Assessing the knowledge, attitudes, behaviors and training needs related to
      infant feeding, specifically breastfeeding, of child care providers.
AB  - OBJECTIVE: The purpose of this study was to assess the knowledge, attitudes,
      behaviors and training needs of child care providers on infant feeding practices,
      specifically breastfeeding. METHODS: Needs assessment surveys for child care
      directors and infant room teachers were developed, tested and mailed to the 277
      Colorado child care centers licensed to care for infants (< or = 12 months);
      1,385 surveys were mailed. RESULTS: A total of 267 surveys were received for an
      overall response rate of 20%. The majority (79%) of infant room teachers and
      directors reported low knowledge on ways to adequately store breastmilk and
      formula. Perceived attitudes on the advantages and disadvantages of breastmilk
      versus formula as well as behaviors associated with offering working mothers a
      supportive breastfeeding environment (e.g. breast pumps available at center,
      offer mothers a place to breastfeed) were also examined. Directors and infant
      room teachers desired updated infant feeding information for themselves, co
      workers and parents. They wanted English and Spanish information regarding
      breastfeeding, formula feeding and introducing solid foods. Eighty-six percent of
      directors and 67% of teachers stated they have Internet access at work. Eighty
      eight percent of directors and 79% of teachers would be interested in an infant
      feeding website. CONCLUSIONS: According to the results of the needs assessment,
      child care directors and infant room teachers are in need of current, accessible
      infant feeding information. Child care directors and infant room teachers desired
      a website with bilingual and best practice infant feeding information specific to
      the needs of child care providers.

PMID- 17557201
TI  - The effects of father involvement during pregnancy on receipt of prenatal care
      and maternal smoking.
AB  - OBJECTIVES: To examine whether women whose partners are involved in their
      pregnancy are more likely to receive early prenatal care and reduce cigarette
      consumption over the course of the pregnancy. This study also examines
      sociodemographic predictors of father involvement during pregnancy. METHODS: Data
      on 5,404 women and their partners from the first wave of the Early Childhood
      Longitudinal Study-Birth Cohort (ECLS-B) were used to examine the association
      between father involvement during pregnancy and maternal behaviors during
      pregnancy. Multivariate linear and logistic regression analyses were used and
      data were weighted to account for the complex survey design of the ECLS-B.
      RESULTS: Women whose partners were involved in their pregnancy were 1.5 times
      more likely to receive prenatal care in the first trimester and, among those who
      smoked at conception, to reduce their cigarette consumption 36% more than women
      whose partners were not involved in the pregnancy (p = .09). Fathers with less
      than a high school education were significantly less likely to be involved in
      their partner's pregnancy, while first-time fathers and fathers who reported
      wanting the pregnancy were significantly more likely to be involved. CONCLUSIONS:
      The positive benefits of father involvement often reported in the literature on
      child health and development can be extended into the prenatal period. Father
      involvement is an important, but understudied, predictor of maternal behaviors
      during the prenatal period, and improving father involvement may have important
      consequences for the health of his partner, her pregnancy, and their child.

PMID- 17557202
TI  - Genetic analysis of cuticular hydrocarbons and their effect on courtship in
      Drosophila virilis and D. lummei.
AB  - Genetical factors controlling the cuticular hydrocarbons (CHC) of Drosophila
      virilis and D. lummei, and the effect of CHC on female attractivity were studied.
      A strong sexual dimorphism was found in D. virilis where (Z)-10-heneicosene and
      (Z)-11-pentacosene were major CHC for males and females, respectively. In D.
      lummei, (Z)-9-pentacosene was the major CHC for both sexes. These CHC are under a
      complex genetical control: the level of male (Z)-10-heneicosene was mainly sex
      linked; chromosome 2 exerted a marked hypermorphic effect on it as well as on
      female (Z)-11-pentacosene; other autosomes had additional smaller effects on the
      CHC. Further, these two species showed differences in the double bond position
      pattern: Monoenes, with double bonds in (Z)-11 or (Z)-13, were more abundant in
      D. virilis (monoenes-vi), while monoenes, with double bonds in (Z)-7 or (Z)-9,
      were more abundant in D. lummei (monoenes-lu). In agreement with previous studies
      of perfumed dummies, experiments with live females showed that a higher
      proportion of (Z)-11-pentacosene or of monoenes-vi induced D. virilis males to
      court sooner. On the other hand, monoenes-lu showed antagonistic effects.

PMID- 17557203
TI  - Polymorphism and genomic structure of the A+T-rich region of mitochondrial DNA in
      the oriental mole cricket, Gryllotalpa Orientalis (Orthoptera: Gryllotalpidae).
AB  - The complete A+T-rich region of mitochondrial DNA has been cloned and sequenced
      from 48 individuals of Gryllotalpa orientalis (Orthoptera: Gryllotalpidae),
      collected from five Korean localities. Thirty-six haplotypes acquired from 48
      individuals were found to range in size from 917 to 925 bp, with a sequence
      divergence from 0.1% to 14.3% and an A+T content from 74.5 to 76.3%.
      Phylogeographic analysis of the G. orientalis haplotypes showed the presence of
      two clearly differentiated mitochondrial clades, separated by 13.4% of a minimum
      uncorrected sequence divergence, which suggests the presence of an unknown,
      similar Gryllotalpa species or a once isolated G. orientalis population.
      Structural analysis in search of the conserved structural elements previously
      described in the caeliferan Orthoptera and Diptera revealed that the G.
      orientalis A+T-rich region harbored a stretch of the [TA(A)]n sequence, which has
      been suggested to be involved in the control of transcription or replication. In
      contrast to the abundance of the sequence stretches containing the stem-and-loop
      structure in the G. orientalis A+T-rich region, the 3' flanking sequence
      "G(A)nT," which is well conserved in a variety of organisms, including the
      caeliferan Orthoptera and Diptera, was not conserved in the A+T-rich region of G.
      orientalis.

PMID- 17557204
TI  - Young women's social and occupational development and mental health in the
      aftermath of child sexual abuse.
AB  - We examined social role functioning and depressive symptoms of young adults who
      were abused as children in data from a longitudinal community sample. Sexually
      abused women and men were more depressed during their senior year of high school,
      and this difference was more pronounced 2 years later. We then examined a
      mediational model to determine whether social functioning explained the course of
      depressive symptoms over this transitional period. Focusing only on young women,
      for whom the prevalence of abuse was much higher, results indicated that two
      thirds of the effect of abuse on depressive symptoms was explained by experiences
      and choices in the domains of work, education and intimate relationships. Having
      less supportive intimate relationships and lower rates of attendance at 4-year
      colleges were particularly important. Findings reveal the key role played by
      early adult interpersonal and occupational development in perpetuating the mental
      health impact of childhood trauma.

PMID- 17557205
TI  - TB perspectives among a sample of Mexicans in the United States: results from an
      ethnographic study.
AB  - OBJECTIVE: A study was conducted to describe the sociocultural aspects of
      tuberculosis (TB) among Mexicans in the U.S. and to provide TB programs with
      practical recommendations for serving this population. METHODS: In-depth,
      structured, open-ended interviews were conducted with 50 persons from Mexico
      living in the U.S. Local bilingual, bicultural researchers conducted the
      interviews with respondents recruited from TB clinics and surrounding
      communities. Both qualitative and quantitative strategies were used to analyze
      the data. RESULTS: We found diverse TB perceptions and attitudes, but few were
      associated with specific participant characteristics. We detected widespread
      misperceptions about TB transmission and low perceptions of risk. Anticipated TB
      stigma among those with no history of disease was qualitatively greater than
      reported stigma among those who had TB disease. We also detected missed
      opportunities for TB education. Reported barriers to care included lack of
      transportation, limited clinic hours, cost of services, inconvenient clinic
      location, and communication problems with staff. CONCLUSIONS: To address the
      diverse needs of Mexican-born clients, we recommend that TB programs provide
      culturally-appropriate, patient-centered care. We suggest several strategies
      aimed at raising risk awareness and reducing stigma. Finally, we encourage
      programs to facilitate access by providing language-appropriate services,
      extending clinic hours, and facilitating transportation.

PMID- 17557206
TI  - The role of effective discharge planning in preventing homelessness.
AB  - Effective discharge planning can contribute significantly to preventing
      homelessness. As part of a larger continuum of care, this process can help people
      reach goals of stable housing, recovery, and increased quality of life in the
      community. Discharge planning identifies and organizes services a person with
      mental illness, substance abuse, and other vulnerabilities needs when leaving an
      institutional or custodial setting and returning to the community. A three
      component model is presented, relating discharge planning to institutional
      assessment and treatment, and to community services. Service challenges,
      innovative programs (based on a state-by-state analysis), and recommendations for
      enhancing discharge planning also are discussed.

PMID- 17557208
TI  - Analysis of protein three-dimension structure using amino acids depths.
AB  - The issue of amino acid depth in proteins gives important insights to our
      understanding of protein's three-dimensional structure. There has already been
      much research done in mathematical and statistical sciences regarding the general
      definitions, properties and algorithms describing the particle depth of spatially
      extended systems. We constructed a method of calculating the amino acids depths
      and applied it to a set of 527 protein structures. We propose the introduction of
      amino acid depth tendency factors for three-dimensional structures of proteins.
      The depth tendency factors relate not only to the hydrophobicity indices but also
      to the electrostatic charge. We found a relationship between the protein size and
      the number of residues using the distance between the deepest residue and surface
      residues. We made a prediction regarding the number of residues on the surface of
      a protein, the deepest amino acid, and the average depth, all of which are fitted
      well to a linear functional relationship with the length of the protein. Finally,
      we have predicted the depths of multiple peptides in protein's three-dimension
      structure.

PMID- 17557209
TI  - Abstracts of the 11th International Congress of the Metastasis Research Society,
      Tokushima, Japan.

PMID- 17557207
TI  - Effect of dopamine agonists on prolactinomas and normal pituitary assessed by
      dynamic contrast enhanced magnetic resonance imaging (DCE-MRI).
AB  - CONTEXT: Dopamine agonists (DA) may act on prolactinoma size and secretion
      through additional effects on adenoma vascularity that can be visualized using
      dynamic contrast enhanced magnetic resonance imaging (DCE-MRI). OBJECTIVE: We
      hypothesized that DAs may exert their effect through a change in tumour
      functional vascularity leading to a reduction of prolactin (PRL) levels and
      tumour size. SUBJECTS AND METHODS: To investigate this, 23 subjects were studied
      comprising five with macroprolactinomas, 11 with microprolactinomas, seven with
      non-lesion hyperprolactinemia and 15 normal volunteers (including five females on
      oral contraceptive pills). Patients with macroprolactinomas were treated with
      cabergoline 4 mg weekly and microprolactinomas were treated with quinagolide 75
      microg daily for the duration of study. DCE-MRI was performed immediately pre
      treatment and at 3-4 days, 1 and 3-4 months after treatment. Normal volunteers
      took three 75 microg quinagolide doses and were scanned pre-treatment and at 3
      days. Data were analysed using the Brix model, producing a measure of vascular
      permeability and leakage space. RESULTS: PRL levels were significantly reduced in
      all patients and volunteers. Vascular parameters decreased significantly for four
      of five macroprolactinomas and all microprolactinomas which were maintained
      during the treatment period (p < 0.01). No changes were seen in normal volunteers
      or non-lesion hyperprolactinemia. One of five macroprolactinomas showed no change
      in either permeability or tumour size. CONCLUSION: Functional prolactinoma
      vascularity differs from non-lesion hyperprolactinemic pituitary and normal
      pituitary, and is responsive to DA therapy. The reduction in vascular parameters
      precedes shrinkage in macroprolactinomas, and if not seen within days of
      treatment may indicate DA resistance requiring early surgery.

PMID- 17557210
TI  - Dietary fiber and colorectal cancer risk: the multiethnic cohort study.
AB  - OBJECTIVE: To investigate the association of dietary fiber with colorectal cancer
      METHODS: A total of 85,903 men and 105,108 women completed a quantitative food
      frequency questionnaire in 1993-1996. A total of 1,138 men and 972 women were
      subsequently diagnosed with adenocarcinoma of the large bowel. Cox proportional
      hazards models were used to calculate multivariate adjusted relative risks (RR)
      and 95% confidence intervals (95% CI) for colorectal cancer. RESULTS: High
      consumers of dietary fiber were more active, less overweight, and less likely to
      be cigarette smokers than low consumers in both sexes. Fiber was inversely
      associated with colorectal cancer risk after adjustment for age and ethnicity in
      men (RR = 0.49; 95% CI, 0.41-0.60, highest vs. lowest quintile) and women (RR =
      0.75; 95% CI, 0.61-0.92). After further adjustment for lifestyle and dietary
      factors, the inverse association remained significant in men (RR = 0.62; 95% CI,
      0.48-0.79), but not in women (RR = 0.88; 95% CI, 0.67-1.14). Adjustment for the
      combination of replacement hormone use with either cigarette smoking or body mass
      index accounted for the lack of association with fiber in women. CONCLUSION:
      Dietary fiber was inversely associated with colorectal cancer risk in men, but
      its relation to replacement hormone use and other factors affected its inverse
      association in women.

PMID- 17557211
TI  - The cost effectiveness of a telephone-based pharmacy advisory service to improve
      adherence to newly prescribed medicines.
AB  - OBJECTIVE: This "proof of concept" study aimed to assess the cost effectiveness
      of pharmacists giving advice via telephone, to patients receiving a new medicine
      for a chronic condition, in England. METHODS: The self-regulatory model (SRM)
      theory was used to guide development of our intervention and used in training
      pharmacists to adopt a patient-centred approach. Non-adherence to new medicines
      for chronic conditions develops rapidly so we developed a study intervention in
      which a pharmacist telephoned patients two weeks after they had started a new
      medicine for a chronic condition. Patients were included if they were 75 or
      older, or were suffering from stroke, cardiovascular disease, asthma, diabetes or
      rheumatoid arthritis, and were randomized into treatment or control arms. Main
      outcome measures were non-adherence and cost to the UK NHS, obtained via a
      questionnaire sent two months after starting therapy. Cost of the intervention
      was also included. Incremental cost effectiveness ratios (ICERs) were generated.
      RESULTS: Five hundred patients were recruited. At 4-week follow-up, non-adherence
      was significantly lower in the intervention group (9% vs 16%, p=0.032). The
      number of patients reporting medicine-related problems was significantly lower in
      the intervention group compared to the control, (23% vs 34% p=0.021). Mean total
      patient costs at 2-month follow-up (median, range) were intervention: pound
      sterling 187.7 (40.6, 4.2-2484.3); control: pound sterling 282.8 (42, 0-3804)
      (p<0.0001). The intervention was dominant (less costly and more effective). If
      the decision maker is not willing to pay anything for one extra adherent patient,
      there is still a 90% probability that the intervention is cost effective.
      CONCLUSIONS: These findings suggest that pharmacists can meet patients' needs for
      information and advice on medicines, soon after starting treatment. While a
      larger trial is needed to confirm that the effect is real and sustained, these
      initial findings suggest the study intervention may be effective, at least in the
      short term, with a reduced overall cost to the health provider.

PMID- 17557212
TI  - Fatal anaphylactoid reaction following ioversol administration.
AB  - We report a fatal intravenous ioversol administration in a 60-year old male
      patient. Although the introduction of new low-osmolar non-ionogenic contrast
      media with a more favourable efficacy-toxicity balance has diminished the side
      effects significantly, everyone involved in radiodiagnostic procedures should be
      aware of the potential life-threatening effects. Especially patients with risk
      factors for side-effects should be monitored carefully.

PMID- 17557214
TI  - Swiss recommendations for the management of varicella zoster virus infections.
AB  - Infections with varicella zoster virus (VZV) are common viral infections
      associated with significant morbidity. Diagnosis and management are complex,
      particularly in immunocompromised patients and during pregnancy. The present
      recommendations have been established by a multidisciplinary panel of specialists
      and endorsed by numerous Swiss medical societies involved in the medical care of
      such patients (Appendix). The aim was to improve the care of affected patients
      and to reduce complications.

PMID- 17557215
TI  - Patient self-management of long-term oral anticoagulation in Switzerland.
AB  - Indications for oral anticoagulation (OAC) have increased in recent years. OAC
      requires frequent monitoring of the prothrombin time to keep the intensity within
      the therapeutic range and to minimise the risk for complications. Patient self
      management (PSM) has been found to improve the quality of OAC. The present study
      aimed to investigate the first 330 patients performing PSM in Switzerland. A
      questionnaire was sent to all patients who followed a teaching program for PSM of
      OAC between 1998 and 2003. Moreover, family physicians were contacted and/or
      discharge letters were obtained from the hospitals or the treating physicians.
      During the study period 13 patients died. Out of the 300 patients providing
      information 254 (85%) still perform PSM. At least one INR determination per two
      weeks was done by 74% of the patients and 25% performed at least one INR
      measurement every 15-30 days. The median time spent within the individual INR
      target range was 72%. No thromboembolic complications occurred, however, among
      the 13 patients who died, 1 had myocardial infarction and 6 died of heart
      failure. When counting these events as arterial thromboembolic complications the
      frequency was 0.6 (95% CI: 0.3-1.3) per 100 patient-years. The frequency of major
      bleeding was 0.6 (95% CI: 0.2-1.3) per 100 patient-years. We conclude from this
      study investigating a real-world patient collective that PSM is suitable and safe
      for the patients identified by their family physicians and successfully trained
      by our training centre.

PMID- 17557216
TI  - Lessons learned from one thousand consecutive colonic resections in a teaching
      hospital.
AB  - Elective colectomies are standard procedures carrying below 1% mortality; by
      contrast, emergency colonic resections remain surgical challenges in compromised
      and/or elderly patients and are associated with high complication rates.

PMID- 17557217
TI  - Complete recovery of visual acuity in two patients with giant cell arteritis.
AB  - Visual recovery in GCA patients is rare even when treated with HDMP. Treatment is
      therefore believed to be effective mainly in saving the unaffected eye. We report
      on two cases with biopsy-proven GCA in which complete recovery of VA occurred
      under intravenous HDMP.

PMID- 17557218
TI  - [Thrombolysis in strokes: time for the neurologist].

PMID- 17557219
TI  - [Impact of warning against procrastination of thrombolysis in ischemic stroke].
AB  - INTRODUCTION: Fibrinolysis in stroke should be carried out as soon as possible,
      but delays occur for various reasons. In the first 17 ischemic infarcts treated
      in our center we confirmed a tendency to exhaust the therapeutic window. We look
      now at whether warnings against this tendency, without other logistical or
      organizational modifications, have had an impact on delays. PATIENTS AND METHODS:
      Neurologists were encouraged to avoid procrastination. When we reached 51 treated
      patients, we compared features and delay times between the first 17 (February,
      2002 to June, 2004) and the 17 most recent cases (October, 2005 to April, 2006).
      Non-parametric tests were used (significant if p < 0.05). RESULTS: Both groups
      were similar clinically and demographically. The onset-arrival time lengthened
      (46 min vs. 75 min; p = 0.01) and scattered. The CT-treatment time halved (57 min
      vs. 30 min; p = 0.001), with consequent shortening of the 'door-to-needle' period
      (121 min vs. 90 min; p = 0.002). The arrival-CT time had remained constant (50
      min vs. 53 min; p = 0.9), thus the total delay from onset did not change
      significantly (165 min vs. 170 min; p = 0.7), and the inverse linear correlation
      between the onset-CT time and the CT-treatment time weakened. CONCLUSIONS:
      Warnings against procrastination appear to be important in terms of shortening
      the delays. The time used for clinical-radiologic evaluation (arrival through CT)
      -about which there had been no action taken--had not been modified, but the time
      employed in the decision to treat (CT-treatment) and the 'door-to-needle' time
      had decreased appreciably. This effective compensatory reduction permitted
      treatment of late-arriving patients, such that although the overall time from
      onset to treatment apparently was not modified, the actual treatment rate
      increased.

PMID- 17557220
TI  - [Prevalence of restless legs syndrome at the office in primary health care].
AB  - INTRODUCTION: Restless legs syndrome (RLS) is a usual neurologic disorder, often
      undiagnosed and treatable, usually associated with sleep disturbance. Our goal
      was to study prevalence of RLS in our practice. PATIENTS AND METHODS:
      Descriptive, cross-sectional study, in a Primary care center. 283 patients 50
      years old or older, which come to the office for any reason, were evaluated with
      a questionnaire about the four essential criteria stated by the international RLS
      study group in 1995. RESULTS: Prevalence of RLS was 11.6% (95% CI: 7.9-15.3%).
      73.5% were women and 26.5% men (ratio 3:1). Only 15% reported major repercussion
      in their quality of life, them we estimated that RLS clinically significant is
      present in 1.9% of our patients. By means of logistic regression only high number
      of consults at the office, daily sleepiness and use of hypnotics were associated
      to RLS. CONCLUSIONS: Prevalence of RLS in more than 50 years old patients is
      high: 11.6% but 1.9% of medically significant RLS. Must be suspected specially in
      women, frequent consultants or with sleep disorders in treatment with hypnotics.

PMID- 17557221
TI  - [Landau-Kleffner syndrome: an analysis of 10 cases in Venezuela].
AB  - INTRODUCTION: Landau-Kleffner syndrome is characterised by acquired aphasia and
      encephalographic alterations that may or may not be accompanied by epileptic
      seizures. AIM. To analyse the clinical and encephalographic features and response
      to treatment of 10 patients with Landau-Kleffner syndrome. PATIENTS AND METHODS:
      We reviewed the patient records, encephalograms and treatment administered to
      patients catalogued as having Landau-Kleffner syndrome. RESULTS: The mean age of
      the patients was 44 months. Of these cases, 60% presented epilepsy when the
      diagnosis was established and 70% were found to have epileptic status during slow
      wave sleep in the encephalographic study. Results showed that 40% corresponded to
      variants of Landau-Kleffner syndrome. No cause of the disease could be
      established in any of the patients. In the neuroimaging study, only one patient
      displayed abnormalities in the magnetic resonance imaging of the brain. All the
      patients received adrenocorticotropic hormone (ACTH)-based treatment, at a dose
      of 1 IU/kg/day for one month, administered together with antiepileptic drugs such
      as valproic acid and clobazam. Convulsive seizures and epileptic status during
      slow-wave sleep disappeared in all the patients. In the patients without
      epileptic status, epileptic activity became less frequent, although it did not
      completely disappear. Aphasia improved considerably, which meant that all the
      patients were able to enroll in normal schools. CONCLUSIONS: We believe that
      early diagnosis, together with suitable and timely management of aphasic patients
      with encephalographic alterations that allow ACTH to be used at low doses, make
      it possible to offer an early education so as to provide maximum recovery from
      the disease.

PMID- 17557222
TI  - [Multiple familial cerebral cavernomatosis].
AB  - INTRODUCTION: Intracraneal vascular malformations are congenital lesions due to
      alterations in the development of arteriocapillary network. Cavernomas are
      present in 0.4% of people, and represent 5-13% of all cerebrovascular
      malformations. They are multilobulated clearly delimited lesions that contain
      blood at different evolution. Cavernomas can be single or multiple, and sporadic
      or familial. Inheritance pattern in familial cases is autosomal dominant and
      three involved genes have been described. CASE REPORTS: We made a retrospective
      review of clinical histories of two patients diagnosed of multiple familial
      cavernomatosis. First patient's onset was with partial seizures. Magnetic
      resonance (MR) showed a frontal cavernoma probable responsible of seizures, and
      other lesions in frontal and parietal lobes. Second patient consulted for
      psychomotor delay and behaviour disorder. MR showed multiple cavernomas. In the
      first patient, one lesion was surgically removed. In second patient, the attitude
      was expectant. In both cases familial study was done and multiple cavernomas were
      found in both parents. CONCLUSIONS: Cavernomas are a type of vascular
      malformations with specific histological features. Usual clinical characteristics
      are seizures and parenchymatous bleeding. The appearance of MR has permitted the
      diagnosis of asymptomatic cavernomas and is currently considered to be the
      technique of choice for this purpose. In familial cases, multiple lesions are
      found in 84%, often in association with family history of seizures. Surgical
      treatment must be considered in patients with symptomatic or progressive lesions
      that are accessible. All cases must be clinically and MR followed.

PMID- 17557223
TI  - [Involvement of neurosteroids in normal and pathological behaviour].
AB  - INTRODUCTION: The nervous system synthesises steroids (then called neurosteroids)
      de novo from cholesterol. These substances play a role in a number of functions
      related to the allosteric modulation of the main ionotropic receptors in the
      central nervous system (CNS). AIM: To describe the most important behavioural and
      cognitive processes in which neurosteroids are involved and which can open up new
      perspectives for research focused above all on their possible therapeutic use in
      pathologies affecting the CNS, such as the cognitive impairment associated to
      neurodegenerative diseases, addictions like alcoholism, anxiety disorders, and
      epilepsy and convulsive behaviour. DEVELOPMENT: We provide a brief outline of the
      concept of neurosteroids, their synthesis, how they act on receptors for
      neurotransmitters and their distribution throughout nerve tissue. We then offer
      an extensive, up-to-date, critical review of the main psychological processes
      that they are involved in. CONCLUSIONS: Neurosteroids offer an important
      therapeutic potential. In epileptiform behaviour, no tolerance is developed to
      the anticonvulsive effects of these substances with repeated administration,
      unlike the case of benzodiazepines, although the study of synthetic analogues and
      agents that step up the synthesis of neurosteroids in the CNS seems to be
      decisive owing to the limitation imposed by the long-term systemic use of
      hormones. In anxiety disorders, they offer several advantages that are comparable
      to the prototypical anxiolytic agents, that is, benzodiazepines, but also their
      chief side effects, such as sedation. In cognitive impairment, the enormous
      potential for cognitive enhancement in animal models is not reproduced in humans
      with dementia, although controlled clinical trials are needed to evaluate the
      benefits and risks of replacement therapy with steroids.

PMID- 17557224
TI  - [Galanthamine versus donepezil in the treatment of Alzheimer's disease].
AB  - AIM: To use comparative studies on the utilisation of the acetylcholinesterase
      inhibitors (AchE), galanthamine and donepezil, to evaluate the effectiveness and
      tolerance of the two drugs in the treatment of the symptoms of Alzheimer's
      disease (AD). DEVELOPMENT: A search was conducted on Medline for papers dealing
      with galanthamine and donepezil that had been published up to February 2007. Six
      comparative studies involving galanthamine and donepezil were found, although
      there are other studies that compare them together with other AchE inhibitors.
      CONCLUSIONS: Both drugs are moderately effective in the treatment of AD.
      Nevertheless, whereas in the case of donepezil there seems to be a positive
      relation between the maximum dosage and response, for galanthamine doses above 24
      mg/day do not seem to offer any improvement. In general, treatment was well
      tolerated in all the studies. Maximum recommended doses (24 mg/day for
      galanthamine versus 10 mg/day for donepezil) were more often reached in patients
      treated with donepezil. The five most common side effects were, in order of
      frequency of presentation: nausea, agitation, vomiting, headache and fainting. In
      the long term, the most frequent side effects from anticholinesterases are,
      generally speaking, muscle cramps, tremors, nightmares, nausea, vomiting,
      fatigue, vertigo and loss of weight. The studies analysed show limitations in the
      design, duration, sample sizes and the titration schemes of the drugs.

PMID- 17557225
TI  - [Persistent trigeminal artery and isolated sixth cranial nerve].

PMID- 17557227
TI  - [Galactosemia: a neurometabolic disease].

PMID- 17557229
TI  - [The mutant spectrum of phenylalanine hydroxylase gene in Northern Chinese].
AB  - OBJECTIVE: To understand the mutant spectrum of phenylalanine hydroxylase (PAH)
      gene in Northern Chinese. METHODS: All the exons and flaking introns of PAH gene
      were detected by PCR-single strand conformation polymorphism (PCR/SSCP) and
      sequencing in 230 patients with phenylketonuria (PKU). RESULTS: (1) A total of 75
      different mutations were detected in 435 out of 460 mutant alleles (94.6%). Among
      them 3 mutations (S251-R252>SfsX89, Y387D and A389G) have not been reported
      previously. The mutations, R243Q, EX6-96A>G, R111X, R413P and Y356X, were the
      prevalent mutations with relative frequencies of 21.7%, 10.2%, 8.3%, 6.5%, and
      6.1% respectively, followed by V399V(4.1%), IVS4-1G>A (3.5%), IVS7+2T>A (2.2%)
      and R241C(2.2%). Most mutations were detected in exons 3, 5, 6, 7, 11 and 12 and
      flaking introns of PAH gene. (2) Ten polymorphism sites were detected in the
      study. Four sites, IVS3-22C>T, IVS10+97G>A, Q232Q and V245V, had high relative
      frequencies of 56.7%, 75.9%, 89.0% and 81.9% respectively. It would suggest that
      the race diversity exists in PAH cDNA sequence. CONCLUSION: The mutation spectrum
      of PAH gene in Northern Chinese is similar to other Asian populations but
      significantly different from European populations.

PMID- 17557230
TI  - [Prenatal diagnosis of Thailand deletion of alpha-thalassemia 1].
AB  - OBJECTIVE: To conduct prenatal diagnosis on the couples carrying Thailand
      deletion (--THAI) alpha-thalassemia 1 and at high risk of having fetus with alpha
      thalassemia. METHODS: Genotypes of couples and fetuses were analyzed by PCR and
      DNA sequencing. RESULTS: Four pregnant women were patients with Hb H diseases of 
      -THAI compounding with alpha-thalassemia 2, while their husbands were
      heterozygote of the Southeast Asian type alpha-thalassemia 1 (--SEA). Another 5
      families, either husbands or wives were heterozygote of --THAI or --SEA. The
      genotypes of their fetuses were as follows: 2 cases with Hb Bart's hydrops
      fetalis syndrome, 1 Hb H disease, 4 alpha-thalassemia heterozygote and 2 normal.
      The DNA sequencing approved the PCR results. CONCLUSION: The study on prenatal
      diagnosis of Thailand deletion alpha-thalassemia 1 is of importance to the
      genetic counseling and prenatal diagnosis of alpha-thalassemia.

PMID- 17557231
TI  - [Overexpression of resistin affect 3T3-L1 adipocyte lipid metabolism].
AB  - OBJECTIVE: To investigate the effect of resistin overexpression on 3T3-L1
      adipocyte lipid and glucose metabolism. METHODS: Expression vector for rat
      resistin gene was constructed and transfected into 3T3-L1 adipocytes. Cell
      differentiation and lipid accumulation was determined by Oil Red O staining.
      Differentiation marker genes (pref-1, C/EBPalpha, FAS) and glucose transporter 4
      (GLUT4) gene mRNA expressions were evaluated by reverse transcription-PCR (RT
      PCR). Triglyceride (TG) and free fatty acids (FFAs) in adipocytes were measured
      by colorimetric kit. RESULTS: (1) In resistin-overexpressed adipocytes, the lipid
      droplets presented at the second day which was earlier than the control cells.
      (2) The expression of C/EBPalpha and FAS genes in resistin-overexpressed
      adipocytes were up-regulated and the pref-1 was down-regulated compared with that
      of the control cells. (3) In resistin-overexpressed adipocytes, cellular TG and
      FFAs levels were significantly increased (P<0.05). (4) There was no difference in
      the expression of GLUT4 gene between 3T3-L1 adipocytes and resistin-overexpressed
      adipocytes (P> 0.05). CONCLUSION: Overexpression of resistin can affect 3T3-L1
      adipocyte lipid metabolism and thereby result in obesity and insulin resistance,
      but have no effect on GLUT4 gene expression.

PMID- 17557232
TI  - [Molecular and cytogenetic study on 18 cases of amenorrhea: the use of
      fluorescence in situ hybridization and high resolution-comparative genomic
      hybridization].
AB  - OBJECTIVE: To explore the use of fluorescence in situ hybridization (FISH) and
      high resolution-comparative genomic hybridization (HR-CGH) techniques in
      amenorrhea study. METHODS: After routine gynecologic examination, ultrasonography
      and endocrine examination, 17 cases of primary amenorrhea and 1 case of secondary
      amenorrhea were analysed by using chromosomal diagnoses including multiplex FISH
      and HR-CGH analyses. RESULTS: Among 17 cases of primary amenorrhea, 7 revealed a
      46,XX karyotype; 10 cases (58.8%) had abnormal karyotype, including 3 cases of
      46,XY females, 2 cases of Turner's syndrome with 45,X and 45,X/46,XX, and other 5
      cases with abnormal structure of X chromosome (including partial monosomy of X,X
      isochromosome and X/Y mosaic). The karyotype of the patient with secondary
      amenorrhea was translocation between X chromosome and euchromosome. CONCLUSION:
      The using of FISH and HR-CGH can correctly diagnose the patients' karyotypes, and
      provide absolutely necessarily medical genetic data for clinical diagnosis and
      therapy.

PMID- 17557233
TI  - [Study on the distribution of Y chromosome haplogroups in Sichuan Han
      population].
AB  - OBJECTIVE: To investigate the distribution characteristics of Y chromosome
      haplogroups in Sichuan Han population. METHODS: Using polymerase chain reaction
      restriction fragment length polymorphism (PCR-RFLP), denatured high performance
      liquid chromatography (DHPLC) and DNA sequencing methods, 18 Y-chromosome
      bialletic markers were detected to type Y chromosome haplogroups in 341
      unselected men from Sichuan Han population. RESULTS: A total of 14 haplogroups
      were observed, in which haplogroups H2 and H4 were identified for the first time
      in Sichuan population, and haplogroups H14 and N* were found firstly in Chinese.
      There was a significant frequency difference of Y haplogroups between Sichuan Han
      population and Southern Han population. CONCLUSION: More comprehensive frequency
      distribution data of Y chromosome haplogroups are obtained in Sichuan Han
      population, which would be helpful for understanding the association of Y
      chromosome background and the susceptibility to male specific diseases such as
      spermatogenic failure, prostate cancer, testical cancer and so on in present
      population.

PMID- 17557234
TI  - Novel partners of S100A8 identified in laryngeal cancer cell lines.
AB  - OBJECTIVE: To explore mechanism of S100A8 in the oncogenesis and development of
      laryngeal cancer. METHODS: Proteins interacting with S100A8 were isolated from
      laryngeal cancer cell lines Hep-2 by immunoprecipitation assay with anti-S100A8
      antibody. The target bands were cut out and identified by maxtrix assisted laser
      desorption/ionization time of flight (MALDI-TOF). The peptide mass fingerprinting
      data of the proteins identified were analyzed based on the Mascot database. The
      NF-kappa B binding sites of the proteins were predicted by P-Match software. The
      binding ability of one of the proteins to S100A8 was confirmed by co
      immunoprecipitation and immunocytochemistry methods. RESULTS: Four proteins
      interacting with S100A8 were obtained, which were hypothetical protein LOC80154,
      MHC class I HLA-B, similar to T-box 1 isoform C and sarcolemmal associated
      protein 1. The four genes were predicted to have NF-kappa B binding sites. MHC
      class I HLA-B, which is one of targets in NF-kappa B pathway, was first confirmed
      to have the binding ability to S100A8. CONCLUSION: The novel partners of S100A8
      identified in the study might be involved in NF-kappa B pathway. The binding
      ability of MHC class I HLA-B to S100A8 implies that S100A8 might function as a
      new member with other proteins including HLA-B in NF-kappa B pathway. These
      findings provide a new clue to further study on the molecular mechanism of S100A8
      in the genesis of laryngeal carcinomas.

PMID- 17557235
TI  - [Cloning, expression, distribution and subcellular localization of AK078438
      gene].
AB  - OBJECTIVE: To investigate the molecular cloning, tissue distribution, tumor
      distribution and the subcellular localization of AK078438 gene. METHODS: Reverse
      transcriptase-polymerase chain reaction (RT-PCR) technique was applied to amplify
      the open reading frame of AK078438 gene. Prokaryotic expressing vector and
      affinity purification were used to get the fusion protein. At mRNA expressing
      levels semi-quantitative RT-PCR was employed for the investigation of its
      distribution in normal rat tissues, tumor cell and mesenchymal stem cell (MSC)
      lines. The eukaryotic expression green fluorescence protein (GFP) fusion protein
      vector was transfected into cells and identified subcellular localization.
      RESULTS: The full open reading frame of AK078438 gene with 1065 bp, 355aa were
      identified. mRNA of the gene distributed in brain, uterus, colon, bone marrow,
      testis and kidney, but not in stomach, liver, the lung, spleen and heart. Murine
      colon adenocarcinoma C26, melanoma B16, Lewis lung carcinoma LL/2 and MSC had the
      gene and mouse myeloma cell line NS-1 and Hepa mouse hepatoma cell line had no
      the gene. The protein was localized in cytoplasm. CONCLUSION: Protein expression,
      expressing profile and subcellular localization of AK078438 gene set the basis
      for further exploration of its functions.

PMID- 17557236
TI  - [Cultivation and karyotype analysis of the human embryonic stem cells HUES4].
AB  - OBJECTIVE: To establish a protocol for culturing of human embryonic stem cells
      (HUES4) without any animal-derived feeder cells and to investigate the karyotype
      stabilities of HUES4 cells after long-term cultivation. METHODS: HUES4 cells were
      cultured on mitomycin C treated MEFs or human foreskin fibroblast feeder cells.
      The pluripotency of the ES cells was analyzed by immunocytochemistry staining to
      detect the expression of pluripotent marker, karyotype of the ES cells at passage
      27, 34, 41, 44 and short tandem repeat (STR) at passage 27 were analyzed.
      RESULTS: The HUES4 cells cultured on human feeder cells were positive for
      alkaline phosphatase activity, SSEA-4, TRA-1-60 and TRA-1-81 staining, but
      negative for SSEA-1. Analysis of karyotype at different passages suggested an
      abnormal karyotype 46, XY, t(9;15)(q22;q26) mosaicism occurred in HUES4, and the
      ratios of abnormal increased with passage. CONCLUSION: HUES4 could be cultured
      without animal-derived feeder cells and the incidence of abnormal karyotype might
      be increased with long-term culture.

PMID- 17557237
TI  - [Searching for genes interacting with human PCIA1 gene by using the bacterial two
      hybrid system].
AB  - OBJECTIVE: To search for the genes which could interact with newly found homo
      sapiens cross-immune reaction antigen (PCIA1) gene and accordingly to provide
      insights into the study of the gene function. METHODS: The Stratagene's
      BacterioMatch Two-Hybrid System and BacterioMatch Fetal Kidney Library were
      adopted and the recombinant bait plasmid pBT-PCIA1 was cotransformated with the
      target plasmid pTRG-cDNA library DNA into the reporter stain. After screening and
      isolation of positive pTRG clones, the target genes were identified by DNA
      sequencing and bioinformation analysis. RESULTS: Among all the seven detected
      target genes, three genes' function were not known, the other four genes had
      important functions. Their mutations or abberant expression resulted in severe
      diseases and overexpression of ACTN4 (actinin, alpha 4), PSAP (prosaposin) or
      EIF3S10 (eukaryotic translation initiation factor 3, subunit 10 theta) could
      promote tumor development and progression. CONCLUSION: The bacterial two-hybrid
      system technique is an efficient method, which can provides insights into the
      study of novel genes' function by detecting protein-protein interactions. This
      study indicates that PCIA1 gene expression correlates with tumor formation,
      invasion and metastasis.

PMID- 17557238
TI  - [Study on clinical features and fluorescence in situ hybridization detections of
      22q11 microdeletion syndrome].
AB  - OBJECTIVE: To investigate clinical features and the diagnosis by fluorescence in
      situ hybridization (FISH) of 22q11 microdeletion syndrome (22q11 DS). METHODS:
      The clinical data of suspects were analyzed, and their peripheral blood samples
      were tested by FISH for microdeletion of 22q11. The diagnosis and correlated
      clinical factors of 22q11 DS were investigated by using the multiple factor
      Logistic regression analysis and Chi-square test. RESULTS: In 64 suspects, 14
      were shown to have 22q11 microdeletion with many different types of malformation,
      and the percentage was 21.9%. The Logistic regression predictive equation for
      22q11 DS was: y=-8.206+2.324x1+2.725x2+1.674x3, P=exp(y)/[1+exp(y)], in which the
      concomit ant variables were facial dysmorphic features (x1), congenital heart
      defects (x2), thymus scarcity/infection problem (x3), the P value meant the
      probability of diagnosis of 22q11 DS. CONCLUSION: Accurate clinical evaluation is
      just as preliminary screening to patients at risk for del22q11. The results of
      FISH test can be predicted by using the suitable Logistic regression equation.

PMID- 17557239
TI  - [Association mapping of schizophrenia loci on chromosome 1 by use of pooled DNA
      genomic screening in eastern Shandong peninsula].
AB  - OBJECTIVE: To find out association mapping of loci related to schizophrenia on
      chromosome 1 with microsatellite markers in DNA pooling samples from
      schizophrenic cases and normal controls in Shandong peninsula. METHODS: A total
      of 31 microsatellite markers on chromosome 1 spaced at approximately 10 cM were
      scanned to two separated DNA pooling samples consisting of 119 schizophrenic
      cases and 119 normal controls respectively. Statistic analysis was performed by
      Chi-square test method to compare the difference between the ratio of each allele
      between the two pooling samples. RESULTS: Significant statistic difference was
      found at D1S2878 between cases and controls, and P< 0.01 at this loci.
      CONCLUSION: D1S2878 locus on chromosome 1 associates with schizophrenia in
      Shandong peninsula. Fine mapping and searching for candidate genes are warranted
      in this region.

PMID- 17557240
TI  - [The effect of inhibiting EOLA1 expression in ECV304 cells].
AB  - OBJECTIVE: To study the effect of inhibiting the expression of endothelial
      overexpressed lipopolysaccharide-associated factor 1 (EOLA1) on proliferation of
      human umbilical vein endothelial cell line ECV304. METHODS: After constructing
      and transfecting EGFP-EOLA1 fusion protein expressive vector into ECV304 cells,
      the transfected cells was cultured in M199 containing G418 for 5 weeks to screen
      the cell line stable expression EGFP-EOLA1 fusion protein. Oligonucleotides
      targeting EOLA1 at different sites were synthesized and inserted into
      pSinencer3.1/H1 vector. Then, the recombinant vector was transfected into the
      cultured ECV304 cells and the inhibiting effect to target gene EOLA1 was
      investigated by observing the green fluorescence in transfected cells under
      inverted fluorescent microscope and by Western blot assay. The proliferation of
      ECV304 cells was numbered when the expression of EOLA1 in ECV304 cells was
      inhibited by RNA interference. RESULTS: The ECV304 cell line stably expressing
      EGFP-EOLA1 fusion protein was constructed and the siEOLA1 interfere vectors can
      knock down EOLA1 gene expression specially. When blocking the expression of EOLA1
      in ECV304 cells,the proliferation of cells slowed down. CONCLUSION: EOLA1 maybe
      has a role on the proliferation of cells.

PMID- 17557241
TI  - [The association of TGF beta1 and AT1R gene polymorphisms with hereditary
      susceptibility and clinical phenotype of HBV-induced liver cirrhosis].
AB  - OBJECTIVE: To investigate the association of TGF beta1 and AT1R gene
      polymorphisms with hereditary susceptibility and clinical phenotype of HBV
      induced liver cirrhosis. METHODS: Peripheral blood samples were collected from
      102 patients with HBV-induced liver cirrhosis and 106 healthy blood donors. The
      polymorphisms of the promoter site -509C/T of TGF beta1 and 1166A/C of AT1R gene
      were determined by PCR-RFLP. RESULTS: The frequency of the homozygote CC of 
      509C/T of TGF beta1 gene in the group of liver cirrhosis was higher than that the
      control group (P<0.05); and the frequency rate of homozygote CC was higher in
      group C than in group A and group B of liver cirrhosis (P<0.05), but there was no
      significant difference in allele frequency among these group (P>0.05). There was
      no significant difference in genotypes and allele frequency of AT1R gene 1166A/C
      between the liver cirrhosis group and the control group (P>0.05). CONCLUSION: The
      polymorphism of the promoter site -509C/T of TGF beta1 gene is associated with
      hereditary susceptibility to liver cirrhosis and severity of HBV-induced liver
      cirrhosis; the polymorphism of AT1R gene 1166A/C is not associated with
      hereditary susceptibility to HBV-induced liver cirrhosis.

PMID- 17557242
TI  - [Mutation analysis of GCH1 gene in Chinese patients with dopa responsive
      dystonia].
AB  - OBJECTIVE: To detect mutations of guanosine triphosphate cyclohydrolase I (GCH1)
      gene in Chinese patients with dopa responsive dystonia (DRD). METHODS: Six
      sporadic patients with DRD were examined. GCH1 gene mutations were detected using
      polymerase chain reaction (PCR), DNA sequence analysis and restriction enzyme
      digestion analysis. One hundred normal people were detected using PCR and
      restriction enzyme digestion analysis. RESULTS: A new point mutation, 151(G-->A)
      in exon one was found in a patient. It lead to substitution of a methionine for
      isoleucine at amino acid 1(M1I). This mutation was not found in normal control
      people. CONCLUSION: The authors report a new heterozygotic point mutation 151(G-
      >A) in GCH1 gene. There are GCH1 gene mutations in Chinese sporadic patients with
      DRD.

PMID- 17557243
TI  - [PINK1 IVS5-5 G>A polymorphism may contribute to the risk of late onset Parkinson
      disease in Chinese].
AB  - OBJECTIVE: To investigate the possible association of IVS5-5G>A polymorphism,
      positioned in the upstream region of exon 5 of PINK1 gene with the risk for
      sporadic late onset Parkinson disease (LOPD) in Chinese. METHODS: Intronic
      regulatory sequence analysis was performed using the web-based in-silico
      analysis. The authors performed an association study using a case-control series
      (comprising 382 LOPD patients and 336 controls, Chinese of Han ancestry).
      Genotyping was performed by PCR-based denaturing high performance liquid
      chromatography (DHPLC) combined with sequencing analyses. Allele and genotype
      frequencies were compared by the Chi-square test. RESULTS: In-silico analysis
      showed that the intronic IVS5-5G>A polymorphism was located within acceptor site
      of exon 5 and may be the functional single polymorphism (SNP) in the regulatory
      region with impact on the splicing of PINK1 gene. Those result yielded
      statistical significant evidence for the association of PINK1 IVS5-5G>A
      polymorphism with risk for typical PD in Chinese Han population (OR=1.95, 95%CI:
      1.29-2.94, P=0.0012). Homozygote of A allele may have increased risk for LOPD
      (OR=2.45, 95%CI: 1.27-4.72, P=0.009). CONCLUSION: The authors provide the first
      evidence that the common genetic variation PINK1 IVS5-5G>A may contribute to the
      risk of LOPD in Chinese population.

PMID- 17557244
TI  - [Clinical study of tetrahydrobiopterin responsive phenylalanine hydroxylase
      deficiency in southern and northern Chinese patients].
AB  - OBJECTIVE: To analyze characteristics of different hyperphenylalaninemia (HPA)
      and to discuss the clinical difference between southern and northern Chinese
      patients with tetrahydrobiopterin (BH4) responsive phenylalanine hydroxylase
      (PAH) deficiency. METHODS: (1)BH4 (20 mg/kg) loading test was performed in all
      108 HPA patients. These patients, 63 males and 45 females, were at a mean age of
      7.05 months. A combined phenylalanine (Phe) and BH4 loading test was carried out
      in the patients who had a basic blood Phe concentration less than 600 micromol/L.
      The urine pterine profile analysis and the dihydropteridine reductase (DHPR)
      activity in dry blood filter spot were analyzed simultaneously. (2)BH4 responsive
      patients were divided to southern and northern groups by their parent's native
      place and geographic boundary determined by Changjiang River. The change of Phe
      concentration after BH4 loading test was compared between the two groups.
      RESULTS: (1)Among the 108 HPA cases, 36 patients (33.3%) were BH4 responsive PAH
      deficiency, 49 (45.4%) were non-BH4 no responsive phenylketonuria (PKU)and
      23(21.3%)were BH4 deficiency (BH4D). The Phe concentration of patients with BH4
      responsive PAH deficiency decreased by 49.24% and 65.35% at 8 h and 24 h after
      oral BH4, 23 in southern group and 13 in northern group among 36 patients. (2)The
      mean Phe concentration at 24 h after loading test in southern and northern groups
      were (217.02+/-189.03) micromol/L and 458.75+/-342.54 micromol/L respectively
      (P<0.05), although the decrease percent of plasma Phe concentration at 2 h, 4 h,
      8 h, 24 h was no distinct difference between southern and northern groups
      (P>0.05). CONCLUSION: Most of mild and moderate HPA patients affected by PAH
      deficiency show plasma Phe concentration decrease >30% in 24 h after oral BH4 20
      mg/kg, few are classic PKU. The responsiveness to BH4 is no difference between
      southern and northern Chinese patients with BH4 responsive PAH deficiency
      according to the decrease percent of plasma Phe concentration, although the Phe
      concentration is lower in southern patients than that in northern patients.

PMID- 17557245
TI  - [Progress of research on biochemistry characteristics of cell-free fetal DNA in
      maternal plasma and its application].
AB  - Cell-free fetal DNA in maternal plasma of pregnant woman, originated from fetal
      and / or placental cells undergoing apoptosis, is mainly the short-sized DNA
      fragments of less than 313 base pairs in length for the sake of nuclear
      endonuclease selectively cleaving fetal DNA during the apoptosis process. The
      mean cell-free circulating fetal DNA in maternal plasma accounted for 3.4% and
      6.2% of plasma total DNA during the early and the late gestation, respectively.
      Owing to its relative abundance, circulating fetal DNA in maternal plasma has now
      become the important DNA source for non-invasive prenatal molecular genetic
      diagnosis and it is widely used in fetal sex-determination, detection of fetal Rh
      (D) sequence in the plasma of the rhesus-negative woman, fetal aneuploidy
      detection, fetal STR genotyping and other clinical applications. Cell-free fetal
      DNA source, concentration, purity, size, distributions and postnatal clearance of
      fetal DNA in maternal plasma as well as the reported clinical applications are
      summarized and discussed in this paper. Based on the molecular characteristics of
      cell-free fetal DNA and the target gene, the using of appropriate molecular
      diagnosis strategy and experimental design as well as reducing the fragment size
      of PCR product and adjusting the PCR conditions to the optimum enable the
      improvement of non-invasive prenatal diagnosis accuracy.

PMID- 17557246
TI  - [Study on the relationship between the polymorphism of p53 gene intron 7 and non
      small cell lung cancer (NSCLC) and p53 mutation in NSCLC tissues].
AB  - OBJECTIVE: To investigate the relationship between p53 gene intron 7 polymorphism
      and non-small cell lung cancer (NSCLC). METHODS: One hundred and five patients
      with NSCLC and 100 controls were selected with case-control analysis. Polymerase
      chain reaction (PCR), Apa I restriction enzyme digestion and agarose gel
      electrophoretic separation were used to identify genotypes of p53 intron 7 in
      peripheral blood. Then, NSCLC biopsy tissues (n=64) and NSCLC paraffin-embedded
      tissues (n=40) were selected for mutation analysis. PCR products of p53 exons 5-8
      were sequenced on an automated sequencer following the identification of intron 7
      genotypes as previously described. RESULTS: In NSCLC patients, the homozygote
      positive for ApaI site in p53 intron 7 was 23.8%, the homozygote negative was
      12.34%, and the heterozygote was 63.8%. Whereas in control group, the homozygote
      positive, the homozygote negative and the heterozygote were 44.0%, 11.0% and
      45.0%, respectively (P<0.01). In the second part, mutation rate of p53 exons 5-8
      was 20.0%, 50.0% and 52.9% in samples with ApaI positive, negative and
      heterozygotes, respectively (P<0.05). CONCLUSION: p53 intron 7 ApaI polymorphism
      may be associated with human NSCLC.

PMID- 17557247
TI  - [Genetic instability detected by flow cytometry: DNA aneuploid and P16 expression
      in biopsy specimens from lung cancer].
AB  - OBJECTIVE: To investigate DNA aneuploid and P16 expression in biopsy specimens
      from lung cancer, and to study genetic instability and the application of flow
      cytometry in lung cancer pernicious degree diagnosis. METHODS: Blood cells and
      cancer cells in biopsy specimens were marked simultaneously with anti-CD45 and
      anti-P16 fluorescent antibody, and the ratio of CD45+ P16+ cells and CD4- P16+
      cells was compared. DNA content in biopsy specimens from lung cancer was detected
      by flow cytometry. RESULTS: Among the 74 cases of lung cancer, there are 46 cases
      of DNA aneuploid (62.2%). Thirty-seven cases of lung cancer expressed P16 lowly
      (50%). Twelve cases of lung cancer only expressed P16 lowly (16.22%), 21 cases of
      lung cancer only expressed DNA aneuploid (28.38%), and 25 cases not only
      expressed P16 lowly but also expressed DNA aneuploid (33.78%). Indexes of malign
      degree, such as P16 low expression or DNA aneuploid could be detected in 58 cases
      among the 74 cases (78.38%) by flow cytometry. CONCLUSION: P16 low expression and
      DNA aneuploid are the indexes of lung cancer malign degree, and flow cytometry
      can be used to study genetic instability and evaluate biopsy specimens from lung
      cancer.

PMID- 17557248
TI  - [Association study on microsatellite polymorphisms of MSX1 gene and nonsyndromic
      cleft lip and palate].
AB  - OBJECTIVE: To investigate muscle segment homeobox 1 (MSX1) microsatellite marker
      distribution and the relationship between MSX1 gene and the genetic
      susceptibility of nonsyndromic cleft lip and palate (NSCLP) in Hunan Hans.
      METHODS: One microsatellite DNA marker CA repeat in MSX1 intron region was used
      as genetic markers. The genotypes of 129 patients with NSCLP and 108 controls
      were analyzed by the techniques of polymerase chain reaction (PCR) and denaturing
      polyacrylamide gel electrophoresis (PAGE). Then case-control study was used to
      conduct association analysis. RESULTS: The allele frequencies of the CA repeat
      microsatellite DNA in Hunan Han normal population were in good agreement with
      Hardy-Weinberg equilibrium. The polymorphism information content and
      heterozygosity of CA repeat microsatellite DNA were 0.50 and 0.50 respectively.
      The allele CA4 frequency in CL/P and CPO group was significantly higher than that
      of normal controls (P<0.05). The genotype CA4,4 frequency was significantly
      higher in CL/P and CPO group than that in normal controls (P<0.05). CONCLUSION:
      The microsatellite DNA marker CA repeat in MSX1 is a good genetic marker. MSX1
      gene is significantly associated with NSCLP in Hunan Hans.

PMID- 17557249
TI  - [Relationship between single nucleotide polymorphisms of paraoxonase 2 and
      stroke].
AB  - OBJECTIVE: To study the relationship between single nucleotide polymorphisms of
      paraoxonase 2 (PON2) and stroke. METHODS: Objects examined comprised of three
      groups: 120 healthy people, 150 patients with cerebral hemorrhage, 180 patients
      with cerebral infarction. The PON2 genotypes were determined with PCR and
      digested by specific restriction enzymes. RESULTS: C311S and G148A polymorphisms
      of PON2 gene existed among population of Chinese Hunan area, with the allele
      frequencies 0.23/0.77 for C/S and 0.57/0.43 for G/A in the control group. There
      was no significant difference of genotype and allele frequency between stroke
      patients and controls (P>0.05). CONCLUSION: C311S polymorphism of PON2 has no
      significant correlation with stroke in Han people of Chinese Hunan area and
      allele C/S is not an independent risk factor for stroke,neither is G148A.

PMID- 17557250
TI  - [Influence of interphase nuclei preparation techniques on fluorescence in situ
      hybridization results in solid tumors].
AB  - OBJECTIVE: To establish a technology platform for the preparation of interphase
      nuclei for the fluorescence in situ hybridization (FISH) detection of solid tumor
      tissues. METHODS: The centromere probe of chromosome 3 was labeled by the random
      primer technique, and then hybridized to interphase nuclei prepared by six
      different methods in order to study the influence on FISH detection. RESULTS:
      Each method of slide preparation had its own characteristic, and could be used
      according to different needs. As regards to FISH, collagenase method got the best
      results. Whereas for frozen samples or small tissues, to prepare printing slides
      was more applicable. CONCLUSION: The comparison of different slide preparation
      methods lays a technology foundation for the FISH application in cancer
      researches and clinical diagnosis of solid tumors.

PMID- 17557251
TI  - [Analysis of alleles 4qA and 4qB of the chromosome 4q subtelomere in Chinese Han
      population].
AB  - OBJECTIVE: To analyze two alleles (4qA and 4qB) distal to D4Z4 of the 4q
      subtelomere in Chinese population, and to elucidate the interrelationship between
      these variants of 4qter and facioscapulohumeral muscular dystrophy (FSHD).
      METHODS: Eighty unrelated healthy individuals from a random Chinese Han
      population were investigated. The genomic DNA was extracted from peripheral blood
      lymphocytes according to the specific procedure designed to minimize DNA
      shearing, then digested with EcoRI, HindIII or double digested with EcoRI and
      BlnI. The cleaved DNA was separated by pulsed field gel electrophoresis (PFGE)
      and Southern blotting with the probes p13E-11, 4qA and 4qB. The sizes of 4q35
      EcoRI/4qA and EcoRI/4qB arrays were obtained by "curve fitting", and the
      frequencies of alleles and genotypes were calculated. Data were analyzed using a
      commercially available statistical package (Version 13.0 SPSS). RESULTS: In
      normal individuals, frequencies of 4qA and 4qB alleles (46.9% and 53.1%) were
      observed of no significant difference (chi(2) = 1.250, P>0.05). The frequency of
      4qA/4qB heterozygote was much higher than that of homozygote (P<0.05). The means
      of EcoRI/4qA and EcoRI/ 4qB arrays (115.8+/-11.9 kb and 98.3+/-8.6 kb) were of
      significant difference (t=23.04, P<0.001). 8.8% (7/80) of the individuals
      displayed a translocation repeat array configuration. 4qB-type EcoRI arrays
      smaller than 35 kb were found in two individuals. CONCLUSION: The structural
      polymorphism of 4qA/4qB alleles within 4q35 and 10q26 is confirmed using PFGE in
      normal Chinese Han population. Although both alleles are almost equally common,
      shorten 4qB-type EcoRI fragment is not pathogenic. The frequency of 4qA/4qB
      heterozygote is significantly higher than that of homozygote.

PMID- 17557252
TI  - [The vitamin D receptor gene Tru I polymorphisms and its effect on the detection
      of Bsm I polymorphisms in Han nationality].
AB  - OBJECTIVE: To explore the polymorphisms of vitamin D receptor (VDR) gene Tru I
      polymorphisms and the influence of this variation on Bsm I polymorphisms in Han
      nationality. METHODS: Venous blood samples from 80 healthy individuals of Han
      nationality were collected and genomic DNA was extracted, VDR Bsm I and Tru I
      were tested by polymerase chain reaction-restriction fragment length polymorphism
      (PCR-RFLP) to analyze the polymorphisms of VDR gene; After using another primers
      to test VDR Bsm I in the same samples, the consistence of each method was
      assessed. RESULTS: The frequencies of the VDR Tru I genotype in the groups were:
      TT 68.7%, Tt 26.3%, tt 5.0%; VDR Bsm I were: BB 6.2%, Bb 52.5%, bb 41.3%; Both
      polymorphisms were under Hardy-Weinberg equilibrium. After using another pair of
      primer, the frequencies of Bsm I genotype were BB 20.0%, Bb 26.2%, bb 53.8%, 22
      genotype Bb changed to genotype BB or genotype bb in comparison with the result
      of first detection. CONCLUSION: The VDR Tru I polymorphism is found in the Han
      nationality, the distribution of this site's polymorphism is different from that
      of other nationalities. The presence of Tru I variation can result in some allele
      of Bsm I genotype drop-out in some study.

PMID- 17557253
TI  - [Analysis of the mutation of BRCA1 gene in 70 Uigur women breast cancer patients
      in Xinjiang].
AB  - OBJECTIVE: To analyze the mutations of BRCA1 in breast cancer patients of Uigur
      women in Xinjiang. METHODS: By using single strand conformation polymorphism
      (SSCP) and DNA sequencing, BRCA1 mutations were detected in 70 Uigur women breast
      cancer cases and 32 cases of benign breast diseases and non-tumor tissue next to
      carcinoma. RESULTS: (1) 12 new loci of BRCA1 gene mutation were detected firstly
      in 70 Uigur women breast cancer patients. (2)The frequency of BRCA1 mutation in
      70 Uigur women breast cancer cases was 12.86% (9/70). The frequency of BRCA1
      mutation in Uigur women early onset breast cancer was 31.82% (7/22), which was
      significantly higher than that in late onset group (2/48, 4.16%) (chi(2) =10.295,
      P<0.01). (3) There were BRCA1 gene polymorphisms in 9 of 70 Uigur women breast
      cancer patients. The loci of polymorphisms in 8 of 9 cases were 3232A>G. (4)In
      the research group two cases of bilateral breast cancer were found with BRCA1
      gene mutation. CONCLUSION: The mutation of BRCA1 gene may be related to Uigur
      women breast cancer and bilateral breast cancer.

PMID- 17557254
TI  - [Twenty Y-STR locus multiplex amplification and genetic polymorphism analysis in
      Han population in Chaoshan area].
AB  - OBJECTIVE: To study genetic polymorphisms of 20 Y-chromosomal short tandem
      repeats (STR) in Chaoshan Han population, and to evaluate their value in forensic
      science. METHODS: Twenty Y-specific STR loci (DYS434, Y-GATA-A10, Y-GATA-H4,
      DYS438, DYS439, DYS443, DYS444, DYS446, DYS447, DYS448, DYS456, DYS458, DYS460,
      DYS520, DYS531, DYS557, DYS622, DYS630, DYS635 and DYS709) were amplified by
      using three fluorescence-labeled multiplex PCR systems and were analyzed by
      ABI310 genetic analyzer. One hundred and fifty-eight unrelated male individuals
      of Han population in Chaoshan area were investigated to determine the
      distribution of allele frequencies and haplotype. RESULTS: The Y-STR multiplexes
      developed had followed the published nomenclature and ISFG guidelines for STR
      analysis. Gene diversity ranged from 0.2506 at DYS434 to 0.8034 at DYS447. A
      total of 157 different haplotypes were observed, and among these, 156 were
      unique, while 1 was found for two times. The haplotype diversity value calculated
      from all 20 loci combined was 0.999998. None of Y-STR allele mutation was
      observed in the 30 father/ son pairs confirmed by autosomal STR analysis.
      CONCLUSION: The results indicate that the 20 Y-STR loci are highly polymorphic
      and fathership genealogy inheritance are stable. The three fluorescence-labeled
      multiplex amplification systems that we constructed are suitable for forensic
      individual identification and paternity testing in Chaoshan area.

PMID- 17557255
TI  - [Distribution characters and linkage disequilibrium analysis of APOM gene
      polymorphisms in Han population of North China].
AB  - OBJECTIVE: To investigate the distribution characters and linkage disequilibrium
      of apolipoprotein M gene (APOM) polymorphisms in Han population of North China.
      METHODS: The single nucleotide polymorphisms (SNPs) in six exons and five introns
      of APOM gene of 330 normal subjects in Han population of North China were
      detected by PCR-restriction fragment length polymorphism and DNA sequencing
      analysis. RESULTS: Three SNPs in Han Chinese were found, including rs805264 of
      intron 1, rs707922 and rs707921 of intron 5 of APOM gene. The frequency
      distribution of these SNPs was different among different races and territory. In
      addition, linkage disequilibrium among the SNPs of rs805264, rs707922 and
      rs707921 of APOM gene was found and A-T-A and G-G-C were predominant haplotypes.
      CONCLUSION: There is apparent linkage disequilibrium among SNPs of APOM gene in
      Han population of North China.

PMID- 17557256
TI  - [Study on SNP polymorphism of mitochondrial DNA D-loop region from Nu ethnic
      population in Yunnan of China].
AB  - OBJECTIVE: To investigate the mitochondrial single nucleotide polymorphism
      (SNP)of Chinese Nu ethnic population from Yunnan region of China and to provide
      basic database for ethnic origin investigation and forensic purpose. METHODS:
      Genomic DNA from the whole blood of 87 unrelated individuals was extracted by
      standard chelex-100. The sequence polymorphism was analyzed by PCR-based assay
      and using ABI 3730 Analyzer to detect many number of relatively common point
      mutations. RESULTS: Sixty-two SNP loci were observed among them with 492 point
      mutations and 59 haploids identified in mitochondrial DNA hypervariable region I
      (mtDNA HVSI). The gene diversity was estimated to be 0.9675,and the random match
      probability was calculated to be 0.0437. CONCLUSION: The result suggests that
      mtDNA HVSISNP database of Nu ethnic population can be a useful tool for forensic
      identity and original research.

PMID- 17557257
TI  - Economic evaluation in renal disease.
AB  - The publication of economic evaluations of health interventions relevant to the
      practice of nephrology is increasing. These are not simply academic exercises,
      but an essential tool to inform optimal use of potentially costly health
      interventions. An overview of the necessary components of economic evaluations is
      provided, with expanded discussion of contemporary issues. These include how
      intermediate health outcomes are handled through mathematical modeling and its
      attendant pros and cons, the role of sensitivity analysis in harnessing
      uncertainty, the potential impact of bias and when it is likely to occur, as well
      as a discussion of how the high costs of ongoing dialysis can impact results.
      Greater understanding of economic evaluations and their potential pitfalls will
      enable appropriate interpretation, and further their use as a tool to maximize
      health benefits, given finite health care resources.

PMID- 17557258
TI  - WNKs: new concepts in the regulation of NaCl and K+ balance.

PMID- 17557259
TI  - Biosimilars: uncharted territory.

PMID- 17557260
TI  - Membranous nephropathy.
AB  - Membranous nephropathy (MN) is a glomerular disease characterized by proteinuria,
      usually in a nephrotic range, and variable natural course. The etiology is
      unknown in many cases, while in some patients, MN may be secondary to infection,
      to other diseases, or to exposure to drugs and toxic substances. In idiopathic
      MN, the antigens are probably located at the base of podocytes, and the
      glomerular lesions occur by the local formation of immune complexes, with
      consequent activation of complement and inflammation triggered by the membrane
      attack complex C5b-9. Patients with severe proteinuria, those with advanced
      tubulointerstitial changes at renal biopsy and those with increased serum
      creatinine at presentation have a poorer prognosis, while patients showing
      complete or even partial remission of proteinuria have a favorable prognosis. The
      indications for and types of treatment are controversial. There is no good
      evidence in favor of therapies based on corticosteroids alone. Cyclophosphamide
      and chlorambucil may increase the probability of remission, but the prolonged use
      of these agents may cause disquieting adverse effects. Good results have been
      obtained by alternating corticosteroids and a cytotoxic agent every other month
      for 6 months. Other potential treatments are represented by cyclosporine,
      synthetic adrenocorticotropic hormone (ACTH), mycophenolate mofetil, rituximab
      and intravenous immunoglobulins. Further studies addressed to recognizing the
      responsible antigen(s), and interventions directed to interfere with the specific
      antibodies, with regulators of glomerular permeability, and/or with factors
      regulating the complement activity might allow us to better understand the
      physiopathology of MN and to organize more specific and effective treatments in
      the near future.

PMID- 17557261
TI  - Autogenous arteriovenous fistula options.
AB  - The Fistula First Breakthrough Initiative (FFBI) shows that development of
      multidisciplinary teams with designated vascular access coordinators is the key
      to success in increasing the appropriate use of the arteriovenous fistula as
      access for hemodialysis. Since nephrologists should communicate expectations to
      surgeons regarding fistula placement and their ability to use the access
      repeatedly, current surgical techniques based on KDOQI guidelines and best
      practices are summarized in this review. These may serve also as bases for the
      education of the surgical community. Autogenous fistula options include primary
      native fistula creation in the forearm, arm and lower extremity which can be
      direct or based on transposed or translocated venous vessels. Optimizing
      autogenous options for hemodialysis requires vessel mapping and a surgeon's
      willingness to invest additional time and effort.

PMID- 17557262
TI  - Vascular mapping techniques: advantages and disadvantages.
AB  - At present, an arteriovenous fistula is the best available access when compared
      with an arteriovenous graft or a tunneled hemodialysis catheter. Preoperative
      vascular mapping has been shown to result in an increased placement of
      arteriovenous fistulae. In general, 3 modalities (physical examination,
      ultrasound examination and angiographic evaluation) are available for vascular
      evaluation. Both arterial as well as venous examination can be conducted using
      physical examination. However, this technique is known to miss veins, especially
      in the obese, and result in exclusion of patients who do not show adequate veins
      on clinical inspection, but who have suitable veins (proven by the other
      modalities) for AVF construction. Ultrasound examination of the vessels is an
      objective assessment. It provides an excellent evaluation of both arteries and
      veins for creation of an arteriovenous fistula. The technique is limited by its
      inability to directly visualize the central veins. Although imaging of the veins
      by the administration of radiocontrast dye optimally visualizes peripheral as
      well as central veins, it exposes the patient to the risk of radiocontrast
      induced nephropathy. This article presents advantages and disadvantages of the 3
      mapping techniques and proposes a strategy to conduct vascular mapping in
      patients with chronic kidney disease.

PMID- 17557263
TI  - Emotional distress and health-related quality of life in patients on
      hemodialysis: the clinical value of COOP-WONCA charts.
AB  - BACKGROUND: A significant percentage of patients on hemodialysis (HD) present
      with affective disorders such as anxiety and/or depression. The purpose of this
      study was to explore adaptive mixed affective disorders of patients on HD and to
      analyze the clinical value of a brief health-related quality-of-life (HRQoL)
      instrument, the COOP-WONCA charts, in our population of HD patient. METHODS:
      Seventy-five patients (mean age 49.2 years; range 20.1-64.9), who had been on HD
      for a mean 110 months (range 6.1-364.5 months) were studied. The Beck Depression
      Inventory (BDI), Hamilton Scale of Depression (HDRS) and Hamilton Scale of
      Anxiety (HARS) were used. To evaluate patient HRQoL, we used the validated
      Spanish version of the COOP-WONCA charts. RESULTS: Of the 75 patients studied,
      44.0% (BDI) and 53.4% (HDRS) had some depressive symptoms which were moderate
      severe in 14.7% (BDI) and in 22.7% (HDRS). Anxiety symptoms were observed in
      46.6% of the patients (13.3% were of moderate-severe degree). There was a high
      level of association between both depression scales (BDI and HDRS) (r=0.70;
      p<0.001), as well as between both scales and the HARS (HDRS, r=0.82; p<0.001;
      BDI, r=0.53; p<0.001). The most affected dimensions of the COOP-WONCA charts were
      "Physical fitness" and "Overall health," whereas the least affected were "Social
      activities" and "Daily activities." The global score of the COOP-WONCA charts was
      associated with the presence of depressive (BDI, r=0.64, and HDRS, r=0.75;
      p<0.001) and anxiety symptoms (HARS, r=0.52; p<0.001). A score of >or= 3
      corresponding to the dimension "Feelings" on the COOP-WONCA charts allowed the
      detection of 81.8% of the patients with clinically significant depressive
      symptoms (BDI >18), with a sensitivity of 96.8% and a specificity of 75% for this
      cutoff point. CONCLUSIONS: A high percentage of patients on HD present with mixed
      emotional disorders (anxiety and/or depression); a good correlation is observed
      between HRQoL and the levels of anxiety and depression in these patients; and
      measuring HRQoL with the COOP-WONCA charts may help diagnose such problems.

PMID- 17557264
TI  - Urine release of systemically administered bone morphogenetic protein hybrid
      molecule.
AB  - BACKGROUND: Although it is well known that TGF-beta circulates, the presence and
      activity of endogenous bone morphogenetic proteins (BMPs) in biological fluids
      has not been studied. Here we investigated the urine secretion of a systemically
      administered BMP hybrid molecule. METHODS: A dimeric recombinant human BMP
      molecule consisting of the BMP-7 prodomain and the BMP-6 mature domain was
      constructed and injected into Sprague Dawley rats. The blood was collected from
      the rats' orbital plexus, and 24-hour urine samples were pooled and purified
      using a heparin sepharose column. Protein identity was confirmed by Western blot
      and by liquid chromatography-mass spectrometry (LC-MS) of the resulting peptides.
      Urine-derived protein from the 35-kDa band was bound to inactive demineralized
      bone matrix and implanted subcutaneously into rats. RESULTS: Western blot
      analysis of sera demonstrated that BMP-7/6 remained intact in the rat plasma and
      could still be visualized 30 minutes after its systemic administration. Two
      protein bands at 35 and 39 kDa were detected with anti-BMP antibodies in the
      urine of rats, corresponding to the mature active BMP-6 dimer and the prodomain
      of BMP-7, respectively. LC-MS analysis detected only peptides derived from the
      BMP-7/6 molecule. Histological analysis of implanted pellets revealed formation
      of a new endochondral bone 14 days following implantation. CONCLUSIONS: These
      results show for the first time that systemically administered BMP-7/6 hybrid
      molecule is secreted into the urine and that its biological activity is
      preserved, suggesting that analysis of BMP in urine might reflect its presence in
      serum.

PMID- 17557265
TI  - Influence of chronic renal insufficiency on left ventricular diastolic function
      in hypertensives without left ventricular hypertrophy.
AB  - BACKGROUND: Patients with chronic renal insufficiency (CRI) have a much greater
      cardiovascular risk than the general population. Moreover, hypertension is common
      in these patients, as is left ventricular hypertrophy (LVH) and diastolic
      dysfunction, which contribute to a worse prognosis. While these findings are well
      established for end-stage renal disease, fewer data are available in mild to
      moderate CRI. Furthermore, little is known about diastolic function in CRI
      patients without LVH. METHODS: We performed a cross-sectional study to evaluate
      LV structure and function in hypertensives with CRI, compared with hypertensives
      with normal renal function (EH), by means of mitral inflow and tissue Doppler
      echocardiography. Patients with LVH were excluded from both groups. RESULTS: CRI
      patients had higher left ventricular end-diastolic diameter, end-systolic
      diameter (p<0.0001 and p=0.0001, respectively) and left ventricular mass index
      (LVMI) (p<0.0001) than EH patients. The CRI group also showed greater alterations
      of the diastolic function indexes than hypertensives: lower E-wave peak velocity
      (p=0.02), E-wave peak velocity to A-wave peak velocity ratio (p=0.03) and early
      diastolic myocardial velocity (p=0.04), higher A-wave peak velocity (p=0.07), E
      deceleration time (p=0.02) and isovolumic relaxation time (p=0.0001). Multiple
      regression analysis demonstrated that renal function was a predictor of LVMI and
      diastolic function independently of age, sex, pulse pressure, body mass index and
      duration of hypertension. CONCLUSIONS: Our data showed a greater alteration of
      diastolic function in the CRI group, in part independent of LVMI. In CRI, factors
      other than LVMI and blood pressure seem to play an important role in causing
      early diastolic dysfunction.

PMID- 17557266
TI  - The Pisa experience of renal biopsies, 1977-2005.
AB  - INTRODUCTION: Although several registries collecting data of patients with kidney
      diseases exist, only a few specifically collect data relating to renal biopsy.
      Kidney biopsy has been performed routinely in Pisa since 1977; the aim of this
      study was to report the relative frequency of nephropathies according to gender,
      age at time of biopsy, clinical presentation and renal function, based on
      histological diagnoses during the years 1977 through 2005. During this time,
      3,810 kidney biopsies were performed, of which 89.3% were from native (n=3,446)
      and 10.7% from transplant kidneys. Throughout this period, 5% of renal biopsies
      were not diagnostic, so in this paper we report data regarding 3,269 native
      kidney nephropathies. METHODS: During the years 1977 through 2005, data for renal
      biopsies were collected on specific registers filled out by clinicians.
      Information collected in the database included a variety of indicators, such as
      clinical anamnesis, creatinine clearance, daily proteinuria, hemoglobin levels,
      blood pressure, height and weight, clinical presentation, and current
      medications. Clinical presentation was defined as urinary abnormalities (UA),
      nephrotic syndrome (NS) and acute nephritic syndrome (ANS). Renal diseases were
      divided into 4 major categories: primary glomerulonephritis (GN), secondary GN,
      tubulointerstitial nephropathies (TIN) and vascular nephropathies (VN). RESULTS:
      From 1977 up to 1987, a mean of 95 +/- 18 renal biopsies/year were performed;
      this number significantly increased to 185 +/- 22 renal biopsies/year (range 138
      200) (p<0.001) in the following period (1988-2005). Renal biopsy was more
      frequently performed in males (59%) compared with females (41%). Of all diseases
      of the native kidney, primary GN was the most frequent (66%), followed by
      secondary GN (25.6%), TIN (4.2%) and VN (4.2%). The type of primary GN with the
      highest frequency was mesangial GN (both IgA and non-IgA) (45.7%), followed by
      membranous GN (23%), focal segmental glomerulosclerosis (19.8%), minimal change
      disease (5.3%), crescentic GN (4.2%) and postinfectious GN (2%). In terms of age,
      renal biopsy was more frequently performed in patients aged 20 to 60 years, and
      nearly 60% of patients presented a glomerular filtration rate (GFR) >60 ml/min at
      the time of biopsy. The main clinical reason for performing renal biopsy was UA,
      in all the types of nephropathies. CONCLUSIONS: We confirm data that renal
      diseases are more frequent in men, with the exception of secondary GN. The mean
      age at diagnosis was 42 years resulting from the tendency not to perform renal
      biopsies in children and in elderly patients. Renal biopsy was mainly performed
      in patients with GFR >60 ml/min and asymptomatic urinary abnormalities suggesting
      concern on the part of clinicians regarding glomerular diseases. The tendency to
      perform renal biopsies has been significantly increasing throughout our follow-up
      period.

PMID- 17557267
TI  - Etiologies of chronic renal failure in Jordanian population.
AB  - BACKGROUND: Chronic renal failure (CRF) is a major medical problem, not only
      because of its prevalence, but also because of its complications, which have a
      huge impact on a person's life, both mentally and socially. By investigating the
      etiologies predisposing patients to CRF, we might be able to give recommendations
      about what should be done to avoid it. METHODS: A questionnaire was filled in
      from patients who presented with CRF to 2 major hospitals in Irbid, Jordan,
      investigating the causes and risk factors for CRF available in those patients.
      RESULTS: A total of 235 patients were diagnosed with CRF in 2 major hospitals in
      Irbid, Jordan. Around 72.8% of these patients were older than 40 years, 53.6%
      were females. Diabetes mellitus was the leading cause of CRF (44.7%); the second
      cause was glomerulonephritis (9.8%); and chronic use of nonsteroidal
      antiinflammatory drugs (NSAIDs) was the third cause (8.9%). CONCLUSION: A large
      percentage of patients had CRF due to diabetes. We provide evidence that our
      prescriptions must be revised, as chronic use of NSAIDs was the third leading
      cause of CRF. Both of these causes are seemingly preventable, and efforts should
      be made to eliminate them from the list of etiologies.

PMID- 17557268
TI  - Peritonitis, peritoneal inflammation and membrane permeability: a longitudinal
      study of dialysate and serum MCP-1 in stable patients on peritoneal dialysis.
AB  - BACKGROUND: Increase in peritoneal membrane permeability (D/P) correlates with
      systemic and peritoneal markers of inflammation and neoangiogenesis. Monocyte
      chemoattractant protein-1 (MCP-1, CCL2) is a potent chemoattractant and activator
      of monocytes/macrophages. We measured the serum (sMCP-1) and dialysate MCP-1
      (dMCP-1) concentrations of stable peritoneal dialysis (PD) patients and studied
      various factors affecting MCP-1 production. We also looked at the correlation of
      dMCP-1 concentrations with change in D/P over 12 months. METHODS: Forty-five
      stable prevalent and 6 new PD patients (22 CAPD, 29 APD) were studied. Median PD
      duration was 21 months (range 1-114). D/P was measured by standardized peritoneal
      equilibration test (PET). Patients with recent peritonitis within 3 months of the
      start of study were excluded. MCP-1 concentrations were measured in serum,
      overnight dialysate and post-PET dialysate, both at baseline and at 12 months by
      ELISA. RESULTS: On univariate analysis, post-PET dMCP-1 concentrations positively
      correlated with sMCP-1 (p=0.0002), duration of PD (p=0.02), dialysate volume
      (p=0.001), peritoneal creatinine clearance (p=0.0002) and D/P (p=0.001). There
      was a negative correlation with residual renal function (p=0.001). dMCP-1
      concentrations were higher in patients with past peritonitis (p=0.001). On
      multivariate analysis, factors independently associated with dMCP-1 were sMCP-1
      (p=0.003) and past peritonitis (p=0.001). Thirty patients completed this study,
      and D/P rose by > 0.1 in 20% patients. dMCP-1 concentrations were higher in
      baseline and 12-month samples in patients with change in D/P >0.1. CONCLUSIONS:
      We conclude that dMCP-1 concentrations are related to past peritonitis and serum
      MCP-1. It is difficult to interpret the relationship of dMCP-1 with change in D/P
      over time due to the small number of patients.

PMID- 17557269
TI  - Should rituximab be the rescue therapy for refractory mixed cryoglobulinemia
      associated with hepatitis C?
AB  - BACKGROUND: Mixed cryoglobulinemia (CG) is a systemic immune complex-mediated
      disease that involves small-to-medium vessel vasculitis, provoked by the CG
      containing immune complexes that precipitate in cold. It is associated with
      hepatitis C virus (HCV) infection in 80% of patients. Mixed CG-mediated
      vasculitis can affect vital organs such as kidney, liver and heart. Laboratory
      parameters show presence of cryoglobulin, and in most cases of mixed CG,
      rheumatoid factor IgM kappa. The current treatment strategy of HCV-associated CG
      includes targeting the viral trigger HCV with a combination of antiviral
      medication, interferon-alpha (IFN-alpha) and ribavirin, or the downstream
      pathogenic events by means of plasmapheresis, steroids or immunosuppression. With
      multiorgan involvement, the antiviral therapy may be limited due to severity of
      renal disease, treatment failure, side effects or contraindications. On the other
      hand, immunosuppressive therapy may be poorly tolerated or ineffective.
      Therefore, new treatment options such as rituximab (RIT), a chimeric monoclonal
      anti-CD20 antibody, have been proposed as a rescue therapy. METHODS: We reviewed
      the literature to evaluate the current evidence in treating HCV-related
      refractory mixed CG. RESULTS: The use of RIT in treatment of HCV-related CG was
      first described by Zaja et al. Since then there have been numerous published case
      series and case reports. So far there has been no randomized controlled trial. In
      the literature, there have been 60 patients with CG treated with RIT. The male to
      female ratio was 14:46. Fifty-three patients were HCV-positive. Forty-six
      patients had mixed type II CG, 7 had type III CG and for 7 the type was not
      specified. Twenty-five patients had renal involvement ranging from proteinuria,
      to nephrotic syndrome, to nephritic syndrome to chronic kidney disease. Eight
      patients had had a renal transplant and were on immunosuppression. Most patients
      responded to RIT, with only 17 of 60 patients relapsing, and 8 of 17 of those
      were rechallenged with RIT with a good response. Total follow-up period varied
      between 3 and 31 months. CONCLUSION: RIT is a suitable rescue therapy in
      recalcitrant CG associated with HCV. There is evidence supporting the use of RIT
      as first-line therapy, as opposed to the proposals of others who would strongly
      recommend antiviral therapy. However, a prospective randomized controlled trial
      is required to evaluate the efficacy and safety of RIT compared with current
      standard therapy, which includes antiviral therapy, immunosuppression and
      plasmapheresis.

PMID- 17557270
TI  - Periglomerular accumulation of dendritic cells in rat crescentic
      glomerulonephritis.
AB  - BACKGROUND: An increased number of major histocompatibility complex (MHC) class
      II-positive cells (OX-6+ cells) were observed in the glomerulus and
      periglomerular interstitium during the course of anti-glomerular basement
      membrane (anti-GBM) crescentic glomerulonephritis (GN) in WKY rats. This study
      aimed to demonstrate that periglomerular OX-6+ cells are dendritic cells (DCs)
      and to clarify their roles in the pathogenesis of this GN. METHODS: Kidney
      sections were stained with the OX-6 and the rat DC marker OX-62 by
      immunohistochemistry, and periglomerular OX-6+ cells were observed by
      immunoelectron microscopy. Renal mRNA expression for CXCL12 was examined by
      reverse transcriptase polymerase chain reaction (RT-PCR) and in situ
      hybridization, and that for IL-1beta was examined by in situ hybridization.
      RESULTS: Immunohistochemistry revealed that most periglomerular OX-6+ cells in
      this GN were ED-1-negative. OX-62+ cells were observed sparsely in normal kidney
      interstitium, and considerably more frequently in periglomerular interstitium in
      this GN. Immunoelectron microscopy confirmed the periglomerular OX-6+ED-1- cells
      had DC morphology. The increased expression of CXCL12 mRNA in the diseased
      glomerulus was shown by RT-PCR. By in situ hybridization, CXCL12 mRNA-expressing
      glomerular cells were the parietal and visceral epithelial cells, which were
      close to the site of periglomerular OX-6+ cell localization. The intense
      expression of IL-1beta mRNA by periglomerular cells was demonstrated by in situ
      hybridization. CONCLUSIONS: The periglomerular distribution of OX-6+ED-1- DCs was
      demonstrated in anti-GBM crescentic GN in WKY rats. These DCs might be
      accumulated in periglomerular interstitium by CXCL12, and play a role in the
      initiation and progression of this GN by producing IL-1beta.

PMID- 17557271
TI  - Sequence and expression of NAPlr is conserved among group A streptococci isolated
      from patients with acute poststreptococcal glomerulonephritis (APSGN) and non
      APSGN.
AB  - BACKGROUND: The relation of nephritis-associated plasmin receptor (NAPlr) as a
      nephritogenic antigen in group A streptococci (GAS), to acute poststreptococcal
      glomerulonephritis (APSGN) and the potential of specific strains to cause APSGN
      are not fully understood. It would be helpful to determine whether certain GAS
      strains from APSGN patients specifically express NAPlr and whether strains from
      non-APSGN patients express lower levels or an altered form of NAPlr. METHODS: The
      sequence and levels of expression of NAPlr were assayed for strains of GAS
      isolated from patients with APSGN, pharyngitis, scarlet fever or toxic shock-like
      syndrome. Findings were evaluated with respect to naplr gene sequence, expression
      level of NAPlr, serotype and disease type. RESULTS: In GAS strains from both
      APSGN and non-APSGN patients, the naplr gene showed few or no nucleotide
      alterations, and both types of GAS strains expressed NAPlr in vitro. There were
      no obvious differences in naplr gene sequence, expression of NAPlr, serotype or
      disease type between the GAS strains. In addition, groups C and G streptococci
      also carried a conserved naplr gene and expressed NAPlr in vitro. CONCLUSIONS:
      These groups of streptococci that express NAPlr should be associated with APSGN,
      and this association may be independent of serotype or disease type.

PMID- 17557272
TI  - Sulodexide for hemodialysis anticoagulation in heparin-induced thrombocytopenia
      type II.
AB  - Heparin-induced thrombocytopenia type II (HIT II) is an immune-mediated
      prothrombotic state. It requires cessation of all forms of heparin exposure. In
      maintenance hemodialysis (HD) patients, alternative anticoagulants (i.e.
      bivalirudin, danaparoid, fondaparinux) may be tried for HD procedure
      anticoagulation. Sulodexide (SLX) - a purified glycosaminoglycan preparation (80%
      heparan sulfate and 20% dermatan sulfate) - is not neutralized by platelet factor
      4 and may be useful in HIT II. A 32-year-old man on continuous ambulatory
      peritoneal dilaysis (CAPD) and with protracted atrial fibrillation was given
      enoxaparin prophylaxis. On day 4, his platelets dropped from 119,000/micronL to
      27,000/micronL and HIT II was diagnosed by positive heparin-induced platelet
      aggregation. While enoxaparin was withdrawn, the platelet count increased and
      remained stable. In the meantime, atrial fibrillation subsided but the patient
      developed pseudomonal peritonitis; the catheter was removed and the patient was
      switched to HD with SLX as an anticoagulant (bolus of 30 mg at HD onset). He was
      uneventfully treated with HD for 6 weeks and then reverted to CAPD. The widely
      available and inexpensive SLX may be a new, effective and potentially promising
      alternative anticoagulant in HD patients with HIT II.

PMID- 17557273
TI  - Predicting risk selection following major changes in Medicare.
AB  - The Medicare Modernization Act of 2003 created several new types of private
      insurance plans within Medicare, starting in 2006. Some of these plan types
      previously did not exist in the commercial market and there was great uncertainty
      about their prospects. In this paper, we show that statistical models and
      historical data from the Medicare Current Beneficiary Survey can be used to
      predict the experience of new plan types with reasonable accuracy. This lays the
      foundation for the analysis of program modifications currently under
      consideration. We predict market share, risk selection, and stability for the
      most prominent new plan type, the stand-alone Medicare prescription drug plan
      (PDP). First, we estimate a model of consumer choice across Medicare insurance
      plans available in the data. Next, we modify the data to include PDPs and use the
      model to predict the probability of enrollment for each beneficiary in each plan
      type. Finally, we calculate mean-adjusted actual spending by plan type. We
      predict that adverse selection into PDPs will be substantial, but that enrollment
      and premiums will be stable. Our predictions correspond well to actual experience
      in 2006.

PMID- 17557274
TI  - Reinvestigating hyperpolarized (129)Xe longitudinal relaxation time in the rat
      brain with noise considerations.
AB  - The longitudinal relaxation time of hyperpolarized (HP) (129)Xe in the brain is a
      critical parameter for developing HP (129)Xe brain imaging and spectroscopy and
      optimizing the pulse sequences, especially in the case of cerebral blood flow
      measurements. Various studies have produced widely varying estimates of HP
      (129)Xe T(1) in the rat brain. To make improved measurements of HP (129)Xe T(1)
      in the rat brain and investigate how low signal-to-noise ratio (SNR) contributes
      to these discrepancies, we developed a multi-pulse protocol during the washout of
      (129)Xe from the brain. Afterwards, we applied an SNR threshold theory to both
      the multi-pulse protocol and an existing two-pulse protocol. The two protocols
      yielded mean +/- SD HP (129)Xe T(1) values in the rat brain of 15.3 +/- 1.2 and
      16.2 +/- 0.9 s, suggesting that the low SNR might be a key reason for the wide
      range of T(1) values published in the literature, a problem that might be easily
      alleviated by taking SNR levels into account.

PMID- 17557275
TI  - Imaging of zymogen granules in fully wet cells: evidence for restricted mechanism
      of granule growth.
AB  - The introduction of wet SEM imaging technology permits electron microscopy of wet
      samples. Samples are placed in sealed specimen capsules and are insulated from
      the vacuum in the SEM chamber by an impermeable, electron-transparent membrane.
      The complete insulation of the sample from the vacuum allows direct imaging of
      fully hydrated, whole-mount tissue. In the current work, we demonstrate direct
      inspection of thick pancreatic tissue slices (above 400 mum). In the case of
      scanning of the pancreatic surface, the boundaries of intracellular features are
      seen directly. Thus no unfolding is required to ascertain the actual particle
      size distribution based on the sizes of the sections. This method enabled us to
      investigate the true granule size distribution and confirm early studies of
      improved conformity to a Poisson-like distribution, suggesting that the homotypic
      granule growth results from a mechanism, which favors the addition of a single
      unit granule to mature granules.

PMID- 17557276
TI  - Magnetic resonance imaging of atherosclerosis by targeting extracellular matrix
      deposition with Gadofluorine M.
AB  - As previously reported, Gadofluorine M-enhanced magnetic resonance imaging
      clearly demarcates atherosclerotic plaques from the normal vessel wall. To date,
      the underlying mechanism has remained unknown. Gadofluorine M is a gadolinium
      containing macrocyclic contrast agent containing hydrophilic and hydrophobic
      moieties. To elucidate the mechanism of accumulation, fluorescently labeled and
      radioactively labeled derivates of Gadofluorine M were used to determine affinity
      and specificity of Gadofluorine M binding to blood serum and plaque components in
      vitro and for the distribution within the plaque of WHHL rabbits in vivo.
      Gadofluorine M binds to serum albumin, leading to a breakdown of micelles after
      intravenous injection. The affinity of Gadofluorine M to serum albumin is k(D) =
      2 micromol/l. Gadofluorine then penetrates the atherosclerotic plaque while bound
      to albumin and then accumulates within the extracellular, fibrous parts of the
      plaque by binding to collagens, proteoglycans and tenascin, having the same
      affinity to these plaque constituents as to albumin. In contrast, weak binding
      was determined to LDL (k(D) = 2 mmol/l) and even no binding to hyaluronic acid.
      The driving force of binding and accumulation is the hydrophobic moiety of the
      molecules interacting with hydrophobic plaque materials. Thus, Gadofluorine M
      accumulates within the fibrous plaque or in the fibrous cap of a plaque
      containing high amounts of extracellular matrix components, but not in the lipid
      rich areas. In combination with high-resolution MRI, Gadofluorine M might enable
      the detection of thin-cap fibroatheromas, also named the vulnerable plaque.

PMID- 17557277
TI  - cAMP induced alterations of Chinese hamster ovary cells monitored by mass
      spectrometry.
AB  - Chinese Hamster Ovary fibroblasts (CHO-K1) have shown different protein contents
      when undergoing differentiation by 3',5'-cyclic adenosine monophosphate (cAMP),
      which is known to induce reverse transformation (RT) from malignancy to
      fibroblast-like characteristics. The mass spectrometry (MS) investigation here
      reported about the behavior of CHO-K1 cells before and after exposure to cAMP
      reveals a change in the composition of nuclear proteins associated to an
      inhibition of the protein expression. Possible implications of this finding on
      the control of cell reverse transformation are discussed.

PMID- 17557278
TI  - Toward the proteomic identification of biomarkers for the prediction of HBV
      related hepatocellular carcinoma.
AB  - Early detection is a key step for effective intervention of hepatocellular
      carcinoma (HCC), the lack of sensitive and specific biomarkers is a major reason
      for the high rate of HCC-related mortality. This report described an integrated
      strategy by combining SELDI-ProteinChip, sophisticated algorithm analysis,
      acetonitrile (ACN) pre-treatment and two-dimensional electrophoresis (2DE)
      peptide mass fingerprinting (PMF) techniques to identify serological markers for
      the prediction of HBV-related HCC. Proteomic profiling of three groups of serum
      specimens from HBV-related HCC (50 cases), HBV infection (45 cases), and normal
      subjects (30 cases) was conducted by using SELDI-ProteinChip system and the
      resulting different protein peaks were subjected to stepwise statistical
      analyses. Three most discriminatory peaks at 5890, 11615, and 11724 Da,
      respectively, were screened out from the statistical algorithm and a predictive
      model based on the three peaks was constructed and tested using the newly
      enrolled serum samples. 2DE was applied to separate and compare the serum samples
      that were pre-treated by ACN precipitation. The protein spots obviously
      intensified in HCC sera in the 2DE region of 12 kDa were identified by PMF to be
      serum SAA, which was validated by SELDI-TOF spectra of HCC sera after
      immunoprecipitation using anti-SAA antibody and by Western blot experiments.
      Given the fact that SAA is not a specific biomarker, further attempt is being
      made to identify the other two most discriminatory peaks to realize the
      possibility of using the predictive model for HCC surveillance and prediction.

PMID- 17557279
TI  - Microsurgical nonmicrovascular flaps in forearm and hand reconstruction.
AB  - Relatively new method in flap's surgery, perforator flaps tends to monopolize
      nowadays the surgeon's interest. The question is: could these flaps be used not
      only as free flaps, as were mainly used until now, but also as local or regional
      flaps? On the basis of our experience with 115 operated cases, we will try to
      demonstrate that a lot of simple or composite defects in the forearm and hand
      could be covered, in selected cases, by using local or regional perforator flaps.
      This may have as result, in the future, a dramatic decrease in the indication for
      free flap transfers. Because these flaps need a microsurgical dissection, but do
      not need microvascular sutures, they could be defined as "microsurgical
      nonmicrovascular flaps." The main advantages of these flaps could be summarized
      as: no microsurgical sutures, no main vascular pedicles sacrifice, same surgical
      field, shorter hospitalization time.

PMID- 17557280
TI  - Cross-leg tibial posterior perforator flap.
AB  - BACKGROUND: In the lower leg posttraumatic pathology, we are frequently
      confronted with tissue defects that are difficult to cover by local or distance
      means, because of either the poor tissue quality or the precarious local vessels.
      One of the still available methods for solving these cases remains the cross-leg
      flap. The authors will try to demonstrate the advantages of this method, by using
      the cross-leg flap based on perforator vessels. METHODS: We are presenting two
      cases for which we practiced a cross-leg perforator flap, based on perforator
      vessels emerging from the posterior tibial artery. RESULTS: The results were
      favorable, demonstrated by immobilization in a comfortable position, perfect flap
      integration, pedicle flap's division at 14-21 days, early postsurgery ambulation.
      CONCLUSIONS: The cross-leg perforator flap diminishes many of the disadvantages
      created by the classic cross-leg flap and can be successfully used in cases in
      which other procedures are prohibited.

PMID- 17557281
TI  - Occupational injury among cooks and food service workers in the healthcare
      sector.
AB  - BACKGROUND: Incidence of occupational injury is anticipated to be high among
      cooks and food service workers (CFSWs) because of the nature of their work and
      the types of raw and finished materials that they handle. METHOD: Incidents of
      occupational injury, resulting in lost time or medical care over a period of 1
      year in two health regions were extracted from a standardized operational
      database and with person years obtained from payroll data, detailed analysis was
      conducted using Poisson regression modeling. RESULTS: Among the CFSWs the annual
      injury rate was 38.1 per 100 person years. The risk of contusions [RR, 95% CI
      9.66 (1.04, 89.72)], burns [1.79 (1.39, 2.31)], and irritations or allergies
      [3.84 (2.05, 7.18)] was found to be significantly higher in acute care facilities
      compared to long-term care facilities. Lower risk was found among older workers
      for irritations or allergies. Female CFSWs, compared to their male counterparts,
      were respectively 8 and 20 times more likely to report irritations or allergies
      and contusions. In respect to outcome, almost all irritations or allergies
      required medical visits. For MSI incidents, about 67.4% resulted in time-loss
      from work. CONCLUSIONS: Prevention policies should be developed to reduce the
      hazards present in the workplace to promote safer work practices for cooks and
      food service workers.

PMID- 17557282
TI  - A study on orientation and absorption spectrum of interfacial molecules by using
      continuum model.
AB  - In this work, a numerical procedure based on the continuum model is developed and
      applied to the solvation energy for ground state and the spectral shift against
      the position and the orientation of the interfacial molecule. The interface is
      described as a sharp boundary separating two bulk media. The polarizable
      continuum model (PCM) allows us to account for both electrostatic and
      nonelectrostatic solute-solvent interactions when we calculate the solvation
      energy. In this work we extend PCM to the interfacial system and the information
      about the position and orientation of the interfacial molecule can be obtained.
      Based on the developed expression of the electrostatic free energy of a
      nonequilibrium state, the numerical procedure has been implemented and used to
      deal with a series of test molecules. The time-dependent density functional
      theory (TDDFT) associated with PCM is used for the electron structure and the
      spectroscopy calculations of the test molecules in homogeneous solvents. With the
      charge distribution of the ground and excited states, the position- and
      orientation-dependencies of the solvation energy and the spectrum have been
      investigated for the interfacial systems, taking the electrostatic interaction,
      the cavitation energy, and the dispersion-repulsion interaction into account. The
      cavitation energy is paid particular attention, since the interface portion cut
      off by the occupation of the interfacial molecule contributes an extra part to
      the stabilization for the interfacial system. The embedding depth, the favorable
      orientational angle, and the spectral shift for the interfacial molecule have
      been investigated in detail. From the solvation energy calculations, an
      explanation has been given on why the interfacial molecule, even if symmetrical
      in structure, tends to take a tilting manner, rather than perpendicular to the
      interface.

PMID- 17557283
TI  - Numerical computations of molecular reactions in associated systems caused by the
      formation of fractal structures.
AB  - The interaction between particles in a system containing fractal clusters has
      been computationally simulated. The fractal structure of the system has been
      demonstrated to determine the kinetic characteristics of particle interaction. If
      a system in an N-dimensional space (N = 2, 3, 4) contains fractal clusters with
      the fractal dimension D > N-1, the rate of interaction of a free particle with
      particles belonging to clusters depends on their concentration according to the
      power law. The exponent gamma of this power law formally corresponds to the
      kinetic order of the reaction with respect to the concentration of particles
      belonging to the clusters. Its value is determined by the free surface of the
      clusters and depends on its fractal dimension D. The results of simulation
      qualitatively agree with the data on high, non-integral orders of many liquid
      phase molecular reactions characterized by self-organization of the medium via
      weak intermolecular interactions, such as hydrogen bonds.

PMID- 17557284
TI  - PyFrag--Streamlining your reaction path analysis.
AB  - The PyFrag program (released as PyFrag2007.01) is a "wrap-around" for the
      Amsterdam Density Functional (ADF) package and facilitates the extension of the
      fragment analysis method implemented in ADF along an entire potential energy
      surface. The purpose is to make analyses of reaction paths and other (in
      principle also multidimensional) potential energy surfaces more transparent and
      user-friendly. PyFrag also automates the analysis of reaction paths in terms of
      the extended activation strain model of chemical reactivity.

PMID- 17557285
TI  - Paclitaxel and ceramide co-administration in biodegradable polymeric
      nanoparticulate delivery system to overcome drug resistance in ovarian cancer.
AB  - The objective of this study was to overcome drug resistance upon systemic
      administration of combination paclitaxel (PTX) and the apoptotic signaling
      molecule C(6)-ceramide (CER) in biodegradable poly(ethylene oxide)-modified
      poly(epsilon-caprolactone (PEO-PCL) nanoparticles. Subcutaneous sensitive (wild
      type) and multidrug resistant (MDR-1 positive) SKOV-3 human ovarian
      adenocarcinoma xenografts were established in female Nu/Nu mice. PTX and CER were
      administered intravenously either as a single agent or in combination in aqueous
      solution and in PEO-PCL nanoparticles to the tumor-bearing mice. There was
      significant (p< 0.05) tumor growth suppression in both wild-type SKOV-3 and
      multidrug resistant SKOV-3(TR) models upon single dose co-administration of PTX
      (20 mg/kg) and CER (100 mg/kg) in nanoparticle formulations as compared to the
      individual agents and administration in aqueous solutions. For instance, in SKOV
      3 wild-type model, more than 4.3-fold increase (p < 0.05) in tumor growth delay
      and 3.6-fold (p < 0.05) increase in tumor volume doubling time (DT) were observed
      with the combination treatment in nanoparticles as compared to untreated animals.
      Similarly, 3-fold increase (p < 0.05) in tumor growth delay and tumor volume DT
      was observed in SKOV-3(TR) model. Body weight changes and blood cells counts were
      used as measures of safety and, except for an increase in platelet counts (p <
      0.05) in PTX + CER treated animals, there was no difference between various
      treatment strategies. The results of this study show that combination of PTX and
      CER in biodegradable polymeric nanoparticles can serve as a very effective
      therapeutic strategy to overcome drug resistance in ovarian cancer.

PMID- 17557286
TI  - Combination of thalidomide and cisplatin in an head and neck squamous cell
      carcinomas model results in an enhanced antiangiogenic activity in vitro and in
      vivo.
AB  - Thalidomide is an immunomodulatory, antiangiogenic drug. Although there is
      evidence that it might be more effective in combination with chemotherapy the
      exact mechanism of action is unclear. Therefore, we investigated its effect in
      combination with metronomically applied cisplatin in a xenotransplant mouse model
      characteristic for advanced head and neck squamous cell carcinomas, its possible
      synergistic action in vitro, and which tumor-derived factors might be targeted by
      thalidomide. Although thalidomide alone was ineffective, a combined treatment
      with low-dose cisplatin inhibited significant tumor growth, proliferation and
      angiogenesis in vivo as well as migration and tube formation of endothelial cells
      in vitro. Noteworthy, the latter effect was enhanced after coapplication of
      cisplatin in nontoxic doses. An inhibitory effect on tumor cell migration was
      also observed suggesting a direct antitumor effect. Although thalidomide alone
      did not influence cell proliferation, it augmented antiproliferative response
      after cisplatin application emphasizing the idea of a potentiated effect when
      both drugs are combined. Furthermore, we could show that antiangiogenic effects
      of thalidomide are related to tumor-cell derived factors including vascular
      endothelial growth factor, basic fibroblast growth factor, hepatocyte growth
      factor and Il-8 some known and with, granulocyte colony stimulating growth factor
      and granulocyte macrophage colony stimulating growth factor, some new target
      molecules of thalidomide. Altogether, our findings reveal new insights into
      thalidomide-mediated antitumor and antiangiogenic effects and its interaction
      with cytostatic drugs.

PMID- 17557287
TI  - A novel TEM contrasting technique for extracellular polysaccharides in in vitro
      biofilms.
AB  - In the past, the visualization of the extracellular matrix of biofilms on an
      ultrastructural level was hampered by shrinkage artifacts. In addition, the
      reproducible contrasting of extracellular polysaccharides (EPS) has not
      satisfactorily been solved. Here we describe a method overcoming these
      difficulties, which produces artifact-free transmission electron microscopic
      (TEM) images using multispecies biofilms grown in vitro. Sufficient contrast was
      achieved by replacing Schiff's reagent with the osmiophilic amino acid
      methionine. In addition, shrinkage was avoided by replacing the classical
      dehydration agents with ethylene glycol and 1,2-pentanediol. Applying this method
      provided images of biofilms with an intact matrix in which differentially
      contrasted bacteria were embedded. All six members of the biofilm consortium
      (Streptococcus sobrinus, Streptococcus oralis, Veillonella dispar, Fusobacterium
      nucleatum, Actinomyces naeslundii, and Candida albicans) could be distinguished.
      Within the matrix, structural differences of EPS, probably due to different
      proportions of alpha-1,3 and alpha-1,6 linkages, were apparent. Fibrilar
      polysaccharides were evident around microcolonies of S. sobrinus, and fluffy
      polysaccharides were detected in the vicinity of S. oralis microcolonies. The
      ultrastructure of biofilms prepared for TEM using this method allows the imaging
      of undistorted EPS as well as the differentiated contrasting of the six microbial
      species of the in vitro biofilm model. This is a major step forward in
      determining the spatial arrangement of microorganisms in biofilms on an
      ultrastructural level.

PMID- 17557288
TI  - Free latissimus dorsi perforator flap for reconstruction of hemifacial atrophy:
      case report.
AB  - Progressive hemifacial atrophy (PHA) is characterized by slow and progressive
      atrophy usually of one side of the face. PHA affects primarily the subcutaneous
      fat and muscle tissues, but may involve the bone. The cause is unknown. The
      treatment is symptomatic and directed at augmentation of the deficient soft
      tissue volume. The reconstructive procedures may combine fat grafts, dermis fat
      grafts, pedicle flaps, bone grafts, microvascular free flaps, and alloplastic
      implants. We report a patient with of PHA whose condition was treated with a free
      latissimus dorsi (LD) perforator flap. The LD perforator flap was suitable for
      the large defect of the patient. It could easily be tailored and thinned to
      follow the facial contour. Minor revisions were needed for esthetic reasons.
      There was neither significant downward gravitation nor wasting of the flap. 23
      months later, the natural appearance of the face was maintained.

PMID- 17557289
TI  - Microsurgery, transplantation, and the terminologies of reconstructive surgery.

PMID- 17557290
TI  - Suppression of mesangial cell proliferation and extracellular matrix production
      in streptozotocin-induced diabetic rats by Sp1 decoy oligodeoxynucleotide in
      vitro and in vivo.
AB  - Transcription factor Sp-1 is an important fibrogenic factor that is involved in
      the pathogenesis of diabetic nephropathy. In this study, we examined the effect
      of Sp1 decoy oligodeoxynucleotides (ODNs) on the extracellular matrix (ECM) gene
      expression in cultured rat mesangial cells (RMC) and streptozotocin (STZ)-induced
      diabetic rats. The ring-type Sp1 decoy ODNs significantly decreased ECM mRNA
      expression and Sp1 binding to the promoter region of these PDGF-induced genes in
      RMC. In addition, the decoy ODNs was introduced into the left renal artery of
      diabetic rat using the hemagglutinating virus of Japan (HVJ)-liposome mediated
      gene transfer method and effectively delivered to the kidney. On 14 days after
      ring-type Sp1 decoy ODNs injection, type IV collagen, fibronectin mRNA, and
      protein expression were markedly decreased, and the rate of urinary creatinine
      excretion was reduced in the ring-type Sp1 decoy ODNs-treated diabetic rats.
      These results indicated that the ring-type Sp1 decoy ODNs would be superior to P
      Sp1 ODNs. Also, the R-Sp1 decoy ODN when introduced in vivo, effectively reduced
      ECM production during the progression of nephropathy. Therefore, ring-type Sp1
      decoy is a promising tool for developing new therapeutic applications for
      progressive diabetic nephropathy.

PMID- 17557291
TI  - Tumor-initiating potency of a novel heterocyclic amine, aminophenylnorharman in
      mouse colonic carcinogenesis model.
AB  - A novel heterocyclic amine, 9-(4'-aminophenyl)-9H-pyrido[3,4-b]indole
      (aminophenylnorharman, APNH), which is formed from nonmutagenic 9H-pyrido[3,4
      b]indole (norharman) and aniline, is mutagenic to bacteria and mammalian cells
      and potently carcinogenic in rats. APNH is detected in human urine samples,
      suggesting that humans are continuously exposed to APNH. In the present study,
      (32)P-postlabelin analysis revealed that the levels of APNH-DNA adduct 24 hr
      after the treatment with APNH (1, 5 and 20 mg/kg body weight) in male ICR mice
      were increased in a dose-dependent manner in the colon and liver. Based on these
      findings, we determined the tumor-initiating potency of APNH in an inflammation
      related and two-stage mouse colon carcinogenesis model. Male Crj: CD-1 (ICR) mice
      were given a single intragastric administration (1, 2, 5 or 10 mg/kg body weight)
      of APNH and subsequent 1-week oral exposure to dextran sodium sulfate (DSS, 2% in
      drinking water). Treatment with APNH and DSS resulted in numerous colon tumor
      development: the incidence and multiplicity of the tumors were the highest in the
      mice received 10 mg/kg body weight of APNH and followed by DSS. Development of
      colon tumors was dose-dependent of APNH. Seven of 9 (77.8%) colonic
      adenocarcinomas developed in mice treated with APNH (10 mg/kg body weight) and
      DSS had beta-catenin gene mutations at codons 32 and 37, being predominantly
      transversion. These findings indicate that APNH has an initiating activity in
      inflamed mouse colon and the APNH-DNA adduct formation correlates with its
      tumorigenic potential.

PMID- 17557292
TI  - Incidence rates of hepatocellular carcinoma in the U.S. and Denmark: recent
      trends.
AB  - Hepatocellular carcinoma (HCC) incidence rates vary by gender, age, time and
      place. Geographic differences in gender-, age- and time-specific HCC incidence
      rates may improve the understanding of HCC risk factors. We computed annual
      standardized HCC incidence rates for the United States (U.S.) 1978-2004 and for
      Denmark 1978-2003. Among U.S. white men aged 45-59 the HCC incidence rates were
      comparable to the Danish rates until 1995, but more than tripled over the
      following 8 years to become over 2.5-fold higher than the Danish rate by 2003,
      with an additional small increase in 2004. HCC rates in black U.S. men aged 45-59
      also increased sharply after 1995. Among women aged 45-59 the U.S. HCC rates were
      elevated in recent years, but did not show the sharp increase after 1995 observed
      among men; the Danish rates showed a decreasing trend throughout 1978-2003. U.S.
      rates in the 60-74 years age groups showed a protracted and gradual increase with
      no evidence of a sharp increase after 1995. In the 60-74 years age group, rates
      for Danish men were comparable to those for U.S. white men, but rates for Danish
      women decreased. The U.S. prevalence rates of hepatitis C virus (HCV) infection
      are 2.1 and 1.1% for men and women, respectively, the Danish 0.2%. The disparity
      in HCV prevalence is the most likely explanation for the differences between
      Danish and U.S. trends in HCC incidence. Intravenous drug use and blood
      transfusions are the major sources of HCV, and we suggest that increased HCV
      infection prevalence among Vietnam era military veterans may contribute to the
      earlier and steeper HCC incidence increase for U.S. men than for U.S. women.

PMID- 17557293
TI  - Regulation of E-cadherin and beta-catenin by Ca2+ in colon carcinoma is dependent
      on calcium-sensing receptor expression and function.
AB  - An siRNA directed against the extracellular calcium-sensing receptor (CaSR) was
      used to down-regulate this protein in CBS colon carcinoma cells. In additional
      studies, we utilized a variant of the parental CBS line that demonstrates CaSR
      expression but does not upregulate this protein in response to extracellular
      Ca(2+). In neither the siRNA-transfected cells nor the Ca(2+)-nonresponsive
      variant cells did inclusion of Ca(2+) in the culture medium inhibit proliferation
      or induce morphological alterations. Extracellular Ca(2+) also failed to induce E
      cadherin production or a shift in beta-catenin from the cytoplasm to the cell
      membrane. In mock-transfected cells and in a Ca(2+)-responsive variant line
      derived from the same parental CBS cells, Ca(2+) treatment resulted in growth
      reduction. This was accompanied by increased E-cadherin production and a shift in
      beta-catenin distribution from the cytoplasm to the cell membrane. Additionally,
      down-regulation of c-myc and cyclin D1 expression was observed in mock
      transfected cells and in the Ca(2+)-responsive variant line (along with reduced T
      cell factor transcriptional activation). Neither c-myc nor cyclin D1 was
      significantly down-regulated in the siRNA-transfected cells or in the Ca(2+)
      nonresponsive variant cells upon Ca(2+) stimulation. In histological sections of
      human colon carcinoma CaSR was significantly reduced as compared to the level in
      normal colonic crypt epithelial cells. Where CaSR expression was high, strong
      surface staining for E-cadherin and beta-catenin was observed. Where CaSR
      expression was reduced, beta-catenin surface expression was likewise reduced.

PMID- 17557294
TI  - Inter-method agreement between O*NET and survey measures of psychosocial exposure
      among healthcare industry employees.
AB  - BACKGROUND: Imputed job characteristics had been used as proxy of exposure to
      working conditions. O*NET database provides job information that could be useful
      to evaluate psychosocial working conditions. METHODS: Consistency and total
      agreement between O*NET and self-reported psychosocial exposure (demand/control
      (DC), effort/reward (ER) proxy models, and emotional labor scale) were compared
      between healthcare specific (12 occupations, 215 workers) and other jobs (12
      occupations, 146 workers). RESULTS: For dimensions of the DC and ER models,
      Spearman correlation and ICC coefficients were, in general, consistently high
      (ICC = 0.61 for decision latitude, 0.41 for rewards, 0.53 for ER ratio, and lower
      for others), particularly in the healthcare specific jobs. CONCLUSION: O*NET and
      questionnaire based psychosocial indicators showed a good job level agreement
      particularly on healthcare specific jobs. O*NET may be a useful source of job
      level psychosocial exposure, especially for the DC and ER models, for healthcare
      occupations within these types of facilities.

PMID- 17557295
TI  - Epstein-Barr virus infection and risk of lymphoma: immunoblot analysis of
      antibody responses against EBV-related proteins in a large series of lymphoma
      subjects and matched controls.
AB  - Epstein-Barr Virus (EBV) is consistently associated with distinct
      lymphoproliferative malignancies and aberrant EBV antibody patterns are found in
      most EBV cancer patients. We evaluate the detection of an abnormal reactive
      serological pattern to EBV (ab_EBV) infection and the risk of lymphoma in a
      multicentric case-control study. Serum samples were collected at study entry from
      1,085 incident lymphoma cases from Spain, France, Germany, Czech Republic, Italy
      and 1,153 age, sex and country matched controls. EBV immunoglobulin G (IgG)
      serostatus was evaluated through a peptide-based ELISA combining immunodominant
      epitopes of EBNA1 (BKRF1) and VCA-p18 (BFRF3). Further, immunoblot analysis was
      performed to evaluate distinct antibody diversity patterns to EBV early antigens
      (EA), besides EBNA1, VCA-p18, VCA-p40 (BdRF1) and Zebra (BZLF1). Patients with
      chronic active EBV infection and aberrant EBV activity were characterized as
      having an abnormal reactive pattern (ab_EBV). Ab_EBV was observed in 20.9% of
      2,238 included subjects with an increased proportion of cases presenting ab_EBV
      as compared to the control population (23.9% vs. 18.0% p = 0.001). Ab_EBV
      positivity was a risk factor for all lymphomas combined (odds ratio [OR] = 1.42,
      95% confidence interval [CI]=1.15-1.74), and specifically for chronic lymphocytic
      leukaemia (OR = 2.96, 95%CI = 2.22-3.95). Lower levels of ab_EBV were observed
      for follicular lymphoma (OR = 0.38, 95%CI = 0.15-0.98). EBV may be involved in a
      larger subset of lymphomas among clinically immunocompetent subjects than
      previously thought, probably explained by an underlying loss of immune control of
      EBV latent infection. Ab_EBV is a useful tool to explore EBV imbalances preceding
      or paralleling possible EBV associated oncogenic events.

PMID- 17557296
TI  - Modulation of cortical oscillatory activity during transcranial magnetic
      stimulation.
AB  - Transcranial magnetic stimulation (TMS) can transiently modulate cortical
      excitability, with a net effect depending on the stimulation frequency (< or =1
      Hz inhibition vs. > or =5 Hz facilitation, at least for the motor cortex). This
      possibility has generated interest in experiments aiming to improve deficits in
      clinical settings, as well as deficits in the cognitive domain. The aim of the
      present study was to investigate the on-line effects of low frequency (1 Hz) TMS
      on the EEG oscillatory activity in the healthy human brain, focusing particularly
      on the outcome of these modulatory effects in relation to the duration of the TMS
      stimulation. To this end, we used the event-related
      desynchronization/synchronization (ERD/ERS) approach to determine the patterns of
      oscillatory activity during two consecutive trains of sham and real TMS. Each
      train of stimulation was delivered to the left primary motor cortex (MI) of
      healthy subjects over a period of 10 min, while EEG rhythms were simultaneously
      recorded. Results indicated that TMS induced an increase in the power of brain
      rhythms that was related to the period of the stimulation, i.e. the
      synchronization of the alpha band increased with the duration of the stimulation,
      and this increase was inversely correlated with motor-evoked potentials (MEPs)
      amplitude. In conclusion, low frequency TMS over primary motor cortex induces a
      synchronization of the background oscillatory activity on the stimulated region.
      This induced modulation in brain oscillations seems to increase coherently with
      the duration of stimulation, suggesting that TMS effects may involve short-term
      modification of the neural circuitry sustaining MEPs characteristics.

PMID- 17557298
TI  - Interrelations between motivational stance, cortical excitability, and the
      frontal electroencephalogram asymmetry of emotion: a transcranial magnetic
      stimulation study.
AB  - Several electrophysiological studies have provided evidence for the frontal
      asymmetry of emotion. In this model the motivation to approach is lateralized to
      the left, whereas the motivation to avoidance is lateralized to the right
      hemisphere. The aim of the present experiment was to seek evidence for this model
      by relating electrophysiological and phenomenological indices of frontal
      asymmetry to a direct measure of cortical excitability. Frontal asymmetrical
      resting states of the electroencephalogram and motivational tendencies indexed by
      the Carver and White questionnaire were compared with neural excitability of the
      left and right primary motor cortex as assessed by transcranial magnetic
      stimulation in 24 young healthy right-handed volunteers. In agreement with the
      model of frontal asymmetry, predominant left over right frontal cortical
      excitability was associated with enhanced emotional approach relative to
      emotional avoidance. Moreover, the asymmetries of brain excitability and approach
      avoidance motivational predispositions were both reflected by frontal beta (13-30
      Hz) electroencephalogram asymmetries. In conclusion, the currently demonstrated
      interconnections between cortical excitability, electrophysiological activity,
      and self-reported emotional tendencies for approach or avoidance support the
      frontal asymmetry of emotion model and provide novel insights into its biological
      underpinnings.

PMID- 17557297
TI  - The extended language network: a meta-analysis of neuroimaging studies on text
      comprehension.
AB  - Language processing in context requires more than merely comprehending words and
      sentences. Important subprocesses are inferences for bridging successive
      utterances, the use of background knowledge and discourse context, and pragmatic
      interpretations. The functional neuroanatomy of these text comprehension
      processes has only recently been investigated. Although there is evidence for
      right-hemisphere contributions, reviews have implicated the left lateral
      prefrontal cortex, left temporal regions beyond Wernicke's area, and the left
      dorso-medial prefrontal cortex (dmPFC) for text comprehension. To objectively
      confirm this extended language network and to evaluate the respective
      contribution of right hemisphere regions, meta-analyses of 23 neuroimaging
      studies are reported here. The analyses used replicator dynamics based on
      activation likelihood estimates. Independent of the baseline, the anterior
      temporal lobes (aTL) were active bilaterally. In addition, processing of coherent
      compared with incoherent text engaged the dmPFC and the posterior cingulate
      cortex. Right hemisphere activations were seen most notably in the analysis of
      contrasts testing specific subprocesses, such as metaphor comprehension. These
      results suggest task dependent contributions for the lateral PFC and the right
      hemisphere. Most importantly, they confirm the role of the aTL and the fronto
      medial cortex for language processing in context.

PMID- 17557299
TI  - Application of oncogenetic trees mixtures as a biostatistical model of the clonal
      cytogenetic evolution of meningiomas.
AB  - Meningiomas are mostly benign tumors that originate from the coverings of brain
      and spinal cord. Typically, they reveal a normal karyotype or monosomy for
      chromosome 22. Rare clinical progression of meningiomas is associated with a
      nonrandom pattern of secondary losses of other autosomes. Deletion of the short
      arm of one chromosome 1 appears to be a decisive step for anaplastic growth in
      meningiomas. We calculated an oncogenetic tree model that estimates the most
      likely cytogenetic pathways of 661 meningioma patients in terms of accumulation
      of somatic chromosome changes in tumor cells. The genetic progression score (GPS)
      estimates the genetic status of a tumor as progression in the corresponding tumor
      cells along this model. Large GPS values are highly correlated with early
      recurrence of meningiomas [p < 10(-4)]. This correlation holds even if patients
      are stratified by WHO grade. We show that tumor location also has an impact on
      genetic progression. Clinical relevance of the GPS is thus demonstrated with
      respect to origin, WHO grade and recurrence of the tumor. As a quantitative
      measure the GPS allows a more precise assessment of the prognosis of meningiomas
      than categorical cytogenetic markers based on single chromosomal aberrations.

PMID- 17557300
TI  - Novel biallelic mutations in MSH6 and PMS2 genes: gene conversion as a likely
      cause of PMS2 gene inactivation.
AB  - Since the first report by our group in 1999, more than 20 unrelated biallelic
      mutations in DNA mismatch repair genes (MMR) have been identified. In the present
      report, we describe two novel cases: one carrying compound heterozygous mutations
      in the MSH6 gene; and the other, compound heterozygous mutations in the PMS2
      gene. Interestingly, the inactivation of one PMS2 allele was likely caused by
      gene conversion. Although gene conversion has been suggested to be a mutation
      mechanism underlying PMS2 inactivation, this is the first report of its
      involvement in a pathogenic mutation. The clinical features of biallelic mutation
      carriers were similar to other previously described patients, with the presence
      of cafe-au-lait spots (CALS), early onset of brain tumors, and colorectal
      neoplasia. Our data provide further evidence of the existence, although rare, of
      a distinct recessively inherited syndrome on the basis of MMR constitutional
      inactivation. The identification of this syndrome should be useful for genetic
      counseling, especially in families with atypical hereditary nonpolyposis colon
      cancer (HNPCC) associated with childhood cancers, and for the clinical
      surveillance of these mutation carriers.

PMID- 17557301
TI  - New malignancies following childhood cancer in the United States, 1973-2002.
AB  - The objectives of our study were to quantify risks for developing new
      malignancies among childhood cancer survivors, identify links between particular
      types of first and subsequent cancer, and evaluate the possible role of
      treatment. A cohort of 25,965 2-month survivors of childhood cancer diagnosed in
      the U.S. during 1973-2002 was identified and followed through SEER cancer
      registries. Observed-to-expected ratios (O/E) were calculated, and Poisson
      regression was used to compare risks among treatment groups. Childhood cancer
      survivors were at nearly 6-fold risk of developing a new cancer relative to the
      general population (O/E = 5.9, 95% CI: 5.4-6.5). Most common were subsequent
      primary cancers of the female breast, central nervous system, bone, thyroid gland
      and soft tissue, as well as cutaneous melanoma and acute non-lymphocytic leukemia
      (ANLL). The greatest risks of subsequent cancers occurred among patients
      diagnosed previously with Hodgkin lymphoma (HL), Ewing sarcoma, primitive
      neuroectodermal tumor, or retinoblastoma. Risk of subsequent solid cancers was
      higher among persons whose initial treatment for childhood cancer included
      radiotherapy, whereas the excess of subsequent ANLL was strongly related to
      chemotherapy. The O/E for subsequent ANLL increased with increasing calendar year
      of initial cancer diagnosis among survivors of cancers other than HL, most likely
      due to increasing use of leukemogenic drugs for solid cancers and non-Hodgkin
      lymphoma. Childhood cancer survivors are at markedly increased risk of developing
      a variety of new cancers relative to the general population, but the magnitude of
      excess risk and specific types of second cancer vary widely by type of first
      cancer.

PMID- 17557303
TI  - Deciphering the signaling events that promote melanoma tumor cell vasculogenic
      mimicry and their link to embryonic vasculogenesis: role of the Eph receptors.
AB  - During embryogenesis, the primordial microcirculation is formed through a process
      known as vasculogenesis. The term "vasculogenic mimicry" has been used to
      describe the manner in which highly aggressive, but not poorly aggressive
      melanoma tumor cells express endothelial and epithelial markers and form
      vasculogenic-like networks similar to embryonic vasculogenesis. Vasculogenic
      mimicry is one example of the remarkable plasticity demonstrated by aggressive
      melanoma cells and suggests that these cells have acquired an embryonic-like
      phenotype. Since the initial discovery of tumor cell vasculogenic mimicry by our
      laboratory, we have been focusing on understanding the molecular mechanisms that
      regulate this process. This review will highlight recent findings identifying key
      signal transduction events that regulate melanoma vasculogenic mimicry and their
      similarity to the signal transduction events responsible for promoting embryonic
      vasculogenesis and angiogenesis. Specifically, this review will focus on the role
      of the Eph receptors and ligands in embryonic vasculogenesis, angiogenesis, and
      vasculogenic mimicry.

PMID- 17557302
TI  - Disruption of fibroblast growth factor receptor 3 signaling results in defects in
      cellular differentiation, neuronal patterning, and hearing impairment.
AB  - Deletion of fibroblast growth factor receptor 3 (Fgfr3) leads to hearing
      impairment in mice due to defects in the development of the organ of Corti, the
      sensory epithelium of the Cochlea. To examine the role of FGFR3 in auditory
      development, cochleae from Fgfr3(-/-) mice were examined using anatomical and
      physiological methods. Deletion of Fgfr3 leads to the absence of inner pillar
      cells and an increase in other cell types, suggesting that FGFR3 regulates cell
      fate. Defects in outer hair cell differentiation were also observed and probably
      represent the primary basis for hearing loss. Furthermore, innervation defects
      were detected consistent with changes in the fiber guidance properties of pillar
      cells. To elucidate the mechanisms underlying the effects of FGFR3, we examined
      the expression of Bmp4, a known target. Bmp4 was increased in Fgfr3(-/-)
      cochleae, and exogenous application of bone morphogenetic protein 4 (BMP4) onto
      cochlear explants induced a significant increase in the outer hair cells,
      suggesting the Fgf and Bmp signaling act in concert to pattern the cochlea.

PMID- 17557304
TI  - Amniote somite derivatives.
AB  - Somites are segments of paraxial mesoderm that give rise to a multitude of
      tissues in the vertebrate embryo. Many decades of intensive research have
      provided a wealth of data on the complex molecular interactions leading to the
      formation of various somitic derivatives. In this review, we focus on the crucial
      role of the somites in building the body wall and limbs of amniote embryos. We
      give an overview on the current knowledge on the specification and
      differentiation of somitic cell lineages leading to the development of the
      vertebral column, skeletal muscle, connective tissue, meninges, and vessel
      endothelium, and highlight the importance of the somites in establishing the
      metameric pattern of the vertebrate body.

PMID- 17557305
TI  - Glutamine synthetase is essential in early mouse embryogenesis.
AB  - Glutamine synthetase (GS) is expressed in a tissue-specific and developmentally
      controlled manner, and functions to remove ammonia or glutamate. Furthermore, it
      is the only enzyme that can synthesize glutamine de novo. Since congenital
      deficiency of GS has not been reported, we investigated its role in early
      development. Because GS is expressed in embryonic stem (ES) cells, we generated a
      null mutant by replacing one GS allele in-frame with a beta-galactosidase
      neomycine fusion gene. GS(+/LacZ) mice have no phenotype, but GS(LacZ/LacZ) mice
      die at ED3.5, demonstrating GS is essential in early embryogenesis. Although
      cells from ED2.5 GS(LacZ/LacZ) embryos and GS(GFP/LacZ) ES cells survive in vitro
      in glutamine-containing medium, these GS-deficient cells show a reduced fitness
      in chimera analysis and fail to survive in tetraploid-complementation assays. The
      survival of heavily (>90%) chimeric mice up to at least ED16.5 indicates that GS
      deficiency does not entail cell-autonomous effects and that, after implantation,
      GS activity is not essential until at least the fetal period. We hypothesize that
      GS-deficient embryos die when they move from the uterine tube to the harsher
      uterine environment, where the embryo has to catabolize amino acids to generate
      energy and, hence, has to detoxify ammonia, which requires GS activity.

PMID- 17557306
TI  - Novel genes involved in Ciona intestinalis embryogenesis: characterization of
      gene knockdown embryos.
AB  - The sequenced genome of the urochordate ascidian Ciona intestinalis contains
      nearly 2,500 genes that have vertebrate homologues, but their functions are as
      yet unknown. To identify novel genes involved in early chordates embryogenesis,
      we previously screened 200 Ciona genes by knockdown experiments using specific
      morpholino oligonucleotides and found that suppression of the translation of 40
      genes caused embryonic defects (Yamada et al. [2003] Development 130:6485-6495).
      We have since examined an additional 304 genes, that is, screening 504 genes
      overall, and a total of 111 genes showed morphological defects when gene function
      was suppressed. We further examined the role of these genes in the
      differentiation of six major tissues of the embryo: endoderm, muscle, epidermis,
      neural tissue, mesenchyme, and notochord. Based on the similarity of phenotypes
      of gene knockdown embryos, genes were categorized into several groups, with the
      suggestion that the genes within a given group are involved in similar
      developmental processes. For example, five were shown to be novel genes that are
      likely involved in beta-catenin-mediated endoderm formation. The type of large
      scale screening used is, therefore, a powerful approach to identify novel genes
      with significant developmental functions, the details of which will be determined
      in future studies.

PMID- 17557307
TI  - A new detection algorithm for image analysis of single, fluorescence-labeled
      proteins in living cells.
AB  - A new algorithm is presented for the detection of single, fluorescence-labeled
      proteins in the analysis of images from living cells. It is especially suited for
      images with just a few (<1 per 10 microm2) fluorescence peaks from individual
      proteins with high background and noise (signal to background ratios as low as 2
      and signal to noise as low as 10). The analysis uses the peaks over threshold
      method from extreme value theory and requires minimal assumptions on the
      underlying distributions. The significant advantage of the method over others is
      the rare occurrence to detect false positives. Some examples of simulated and
      real data are given as comparisons. The algorithm is implemented in MATLAB.

PMID- 17557310
TI  - Sensate scaffolds coupled to telemetry can monitor in vivo loading from within a
      joint over extended periods of time.
AB  - Polymer scaffolds have been used as a tool to provide growth and integration of
      engineered tissue substrates to repair damaged tissues in many organ systems
      including articular cartilage. Previous work has shown that "sensate" scaffolds,
      with integrated strain gauges have the potential for use as both a delivery
      vehicle for engineered cartilage as well as a device that can measure real time,
      in vivo joint loading. The purpose of this study was to use an implanted
      subminiature telemetry system to collect in vivo joint loading measurements over
      an extended period following placement of a "sensate" scaffold. Measurements were
      collected from seven of nine sensors that were implanted into the stifles of
      three canines. The limb loading rates and load distribution through gait were
      dependent on stride time but did not vary with time post op. The peak loads were
      not dependent on stride time but significantly increased with time post op. This
      demonstrated that peak loading measured with "sensate" scaffolds can be used to
      monitor healing. The portability of the "sensate" scaffolds coupled to telemetry
      systems highlights the potential use of this system in a clinical research
      setting to gather important information to improve tissue engineering and
      rehabilitation regimens.

PMID- 17557311
TI  - Cytotoxicity evaluation of an antibacterial dentin adhesive system on established
      cell lines.
AB  - Clearfil Protect Bond is a new dental bonding agent recently introduced into
      clinical practice. It contains an antibacterial monomer that contributes to its
      antibacterial profile. The aim of the present study was to evaluate cytotoxic
      effect of Clearfil Protect Bond against three established fibroblastic cell
      lines, in comparison with four commonly used adhesive materials (Adper Scotchbond
      1, Excite, Tyrian SPE, and One Step plus). The experiments were performed using
      RPC-C2A, BHK21/C13, and MRC5 cell lines. Test specimens, either cured or uncured,
      were placed in a culture medium and the extraction media were used as
      experimental material. The effect of the bonding materials was assessed by a
      modified sulforhodamine-B assay after 24 and 48 h of exposure. All tested agents
      exhibited an antiproliferative effect on cells, the effect on RPC-C2A being the
      most marked. Extraction media from the uncured materials were without exception
      highly cytotoxic. In the experiments performed using extraction medium from cured
      material, Clearfil Protect Bond appeared to be the least toxic material, followed
      by Tyrian SPE and One Step plus. Adper Scotchbond 1 and Excite exhibited the
      strongest cytotoxic effect. The cell survival percentage ranged between 66 and
      97% for Clearfil Protect bond, 15 and 82% for Tyrian SPE, 28 and 58% for One Step
      plus, 2 and 28% for Excite, and 1 and 6% for Adper Scotchbond 1. Taking into
      consideration the limitations of an in vitro study, our results indicate that the
      new antibacterial dental adhesive system is suitable for clinical application.

PMID- 17557312
TI  - Respiratory irregularity and stress hormones in panic disorder: exploring
      potential linkages.
AB  - Dysregulation within both respiratory control systems and the hypothalamic
      pituitary adrenal (HPA) axis has been implicated in the pathophysiological of
      panic disorder. However, potential linkages between respiration and the HPA axis
      have rarely been examined in panic patients. We have previously published
      neuroendocrine and psychophysiological response data from a laboratory panic
      model using the respiratory stimulant doxapram. We now present a new,
      theoretically driven re-examination of linkages between HPA axis and respiratory
      measures in this model. Previous analyses showed elevated corticotropin (ACTH)
      and persistent tidal volume irregularity in panic patients, due to a high
      frequency of sighs. Regression analyses now show that tidal volume irregularity
      and sigh frequency were strongly predicted by pre-challenge ACTH levels, but not
      by subjective distress or panic symptoms. We predicted this relationship on the
      basis of our hypothesis that both the HPA axis and respiratory control systems
      may be reactive to contextual cues such as novelty or anticipation of future
      challenge. Follow-up work is needed to directly test this hypothesis.

PMID- 17557313
TI  - Short psychodynamic supportive psychotherapy, antidepressants, and their
      combination in the treatment of major depression: a mega-analysis based on three
      randomized clinical trials.
AB  - The efficacy of Short Psychodynamic Supportive Psychotherapy (SPSP) has not yet
      been compared with pharmacotherapy. A mega-analysis based on three original
      Randomized Clinical Trials (RCTs) was performed. Patients with (mild to moderate)
      major depressive disorder were randomized in (24 weeks) SPSP (n = 97),
      pharmacotherapy (n = 45), or their combination (n = 171). Efficacy was assessed
      by the Hamilton Depression Rating Scale (HDRS), Clinical Global Impression of
      Severity and of Improvement (CGI-S), the Symptom Checklist (SCL; depression
      subscale) and the Quality of Life Depression Scale (QLDS). Pearson chi(2)
      calculations were used to compare success rates. Analyses of covariance (ANCOVAs)
      were used to test inter-group differences. Success rates indicated that
      independent observers (HDRS) found no differences in symptom reduction between
      SPSP and pharmacotherapy (P = 0.214), but therapists (CGI-S, P = 0.026), and
      patients (SCL, P = 0.036) favored SPSP. Combined therapy was found superior to
      pharmacotherapy by all three (patients (P = 0.000), therapists (P = 0.024),
      independent observers (P = 0.024)). Independent observers (P = 0.062) and
      therapists (P = 0.430) found no differences between combined therapy and SPSP,
      but patients (P = 0.016) found combined therapy to be superior. As far as quality
      of life is concerned, success rates indicated that patients (QLDS) found no
      differences between SPSP and pharmacotherapy (P = 0.073) or between SPSP and
      combined therapy (P = 0.217). However, they found combined therapy superior to
      pharmacotherapy (P = 0.015). The results of the mega-analysis suggest that
      combined therapy is more efficacious than pharmacotherapy. SPSP and
      pharmacotherapy seem equally efficacious, except for some indications that
      patients and therapists favor SPSP for symptom reduction. Combined therapy and
      SPSP also seem equally efficacious, except that patients think that the first is
      better in symptom reduction.

PMID- 17557314
TI  - Transfusional iron burden and liver toxicity after bone marrow transplantation
      for acute myelogenous leukemia and hemoglobinopathies.
AB  - BACKGROUND: While it is appropriate to treat transfusional iron overload to limit
      end-organ injury after bone marrow transplantation (BMT) for beta-thalassemia
      major (TM), this approach after BMT for sickle cell disease (SCD) and
      hematological malignancies has not been studied. PROCEDURE: Fifteen children with
      SCD (n = 4), TM (n = 6), or acute myelogenous leukemia (AML, n = 5) underwent HLA
      identical sibling BMT between 2000 and 2003. Prospective evaluations of iron
      biomarkers were performed and the three groups were compared. RESULTS: The pre
      BMT duration and volume of RBC transfusions varied among the three groups, but
      baseline ferritin and liver iron concentration (LIC) were similar. In contrast,
      liver histology differed. Liver inflammation was present in four TM patients and
      portal fibrosis was observed in five TM and one SCD patient. Hepatic veno
      occlusive disease (VOD) developed in 5 of 15 patients. VOD was not associated
      with age, ferritin, ALT, or transfusions, but an association with liver
      inflammation and elevated LIC was suggested. Phlebotomy was performed in five
      patients after BMT. Changes in LIC were minimal in non-phlebotomized patients (P
      = 0.02). CONCLUSION: Iron biomarkers demonstrated significant iron overload
      before BMT in patients with malignant and non-malignant disorders. However, iron
      overload was associated with liver inflammation and VOD primarily in TM patients.
      The clinical significance of iron overload in patients after BMT remains
      uncertain, but this is the first study to suggest that VOD may be associated with
      transfusional iron burden.

PMID- 17557315
TI  - Childhood trauma and obsessive-compulsive symptoms.
AB  - Childhood trauma is known to predispose to a variety of psychiatric disorders,
      including mood, anxiety, eating, and personality disorders. However, the
      relationship between childhood trauma and obsessive-compulsive symptoms has not
      been well studied. This study examines the relationship between childhood trauma,
      personality facets, and obsessive-compulsive symptoms in 938 college students
      using the Childhood Trauma Questionnaire, the Leyton Obsessional Inventory, and
      the NEO Personality Inventory-Revised. Between 13 and 30% of subjects met
      criteria for childhood trauma, with emotional neglect the most commonly reported
      experience. There was a small but significant association between obsessive
      compulsive symptoms and childhood trauma, specifically emotional abuse and
      physical neglect, all of which was accounted for by co-occurring anxiety
      symptoms. An independent association was also seen between emotional abuse,
      physical abuse, and high levels of obsessive-compulsive symptoms ("probable
      obsessive-compulsive disorder"), which remained significant in the context of co
      occurring anxiety symptoms. A similar association was seen between obsessive
      compulsive symptoms and conscientiousness, and between emotional neglect and
      sexual abuse and conscientiousness, suggesting that an indirect role for
      childhood trauma in the development of obsessive-compulsive symptoms may also
      exist.

PMID- 17557316
TI  - The relationship between quality of life and levels of hopelessness and
      depression in palliative care.
AB  - There is growing interest in the psychological distress and quality of life of
      cancer patients. The aim of this study was to compare the responses of 102
      advanced cancer patients on a quality of life scale (as measured by the SF12)
      with the Beck Depression Inventory (BDI) and the Beck Hopelessness Scale (BHS),
      as well as the impact of depression and hopelessness on quality of life.
      Significant associations were found between gender (P=.027), performance status
      (P=.003), opioids (P=.002), depression (P<.0005), and hopelessness (P<.0005) with
      the SF12-Mental Component Score (MCS). Gender (P=.07), metastasis (P=.001),
      opioids (P=.0005), and education (P=.045) correlated significantly with SF12
      Physical Component Score (PCS). In the prediction of MCS, the dimensions of age,
      hopelessness, gender, and performance status were statistically significantly
      high (P<.0005), explaining 48% of variance. For PCS, the predictor variables were
      education, metastasis, and opioids (25% of variance). Quality of life, in this
      patient population, was predicted by the level of hopelessness and patients'
      demographic and clinical characteristics.

PMID- 17557317
TI  - A web-based interactive developmental table for the ascidian Ciona intestinalis,
      including 3D real-image embryo reconstructions: I. From fertilized egg to
      hatching larva.
AB  - The ascidian chordate Ciona intestinalis is an established model organism
      frequently exploited to examine cellular development and a rapidly emerging model
      organism with a strong potential for developmental systems biology studies.
      However, there is no standardized developmental table for this organism. In this
      study, we made the standard web-based image resource called FABA: Four
      dimensional Ascidian Body Atlas including ascidian's three-dimensional (3D) and
      cross-sectional images through the developmental time course. These images were
      reconstructed from more than 3,000 high-resolution real images collected by
      confocal laser scanning microscopy (CLSM) at newly defined 26 distinct
      developmental stages (stages 1-26) from fertilized egg to hatching larva, which
      were grouped into six periods named the zygote, cleavage, gastrula, neurula,
      tailbud, and larva periods. Our data set will be helpful in standardizing
      developmental stages for morphology comparison as well as for providing the
      guideline for several functional studies of a body plan in chordate.

PMID- 17557318
TI  - Symptom presentation and classroom functioning in a nonclinical sample of
      children with social phobia.
AB  - This study investigates symptom presentation and school functioning in a
      nonclinical sample of children with social phobia (SP). Forty-five children with
      SP were identified via school-wide screenings and follow-up diagnostic
      interviews. Analyses examined types and intensity of fears, number of social
      situations avoided, interpersonal relationships, and classroom functioning. To
      identify characteristics unique to social phobic children, children with SP (n =
      45) were compared to anxious children without SP (n = 56) on the above variables.
      Comorbidity in children with SP and factors associated with SP severity were also
      evaluated. Compared to anxious children without SP, children with SP feared and
      avoided a significantly greater number of social situations. In addition, they
      were significantly more likely to have trouble with making friends and to prefer
      being alone rather than with peers. All children with SP met criteria for at
      least one comorbid disorder. Significant factors explaining child-reported
      severity of SP were number of social situations avoided and intensity of fears.
      Greater severity of SP was significantly associated with poorer social skills,
      poorer leadership skills, greater attention difficulties, and greater learning
      problems in the classroom. It is important to understand the symptom presentation
      of SP so that children with SP are identified early and effective interventions
      are instituted. This is especially critical given the impact of SP on school
      functioning.

PMID- 17557319
TI  - Randomized control trial of a behavioral intervention for overweight women:
      impact on depressive symptoms.
AB  - Phone and Internet-based interventions can improve the management of depression
      in primary care, and interventions using these communication channels are
      increasingly used to improve behaviors such as diet and physical activity.
      Increased physical activity has been shown to improve depressive symptoms, but to
      date there are no reports of the effects of a phone and Internet diet and
      exercise intervention on symptoms of depression in patients seen in primary care.
      This study assessed depressive symptoms in 401 participants in a randomized
      control trial of a 12-month primary care, phone and Internet-based behavioral
      intervention for overweight women. A one-way analysis of variance examining the
      mean change in Center for Epidemiological Studies Depression (CESD) score from
      baseline to 12 months, controlling for age, education, marital status, and
      employment showed that those receiving the intervention significantly decreased
      their CESD scores (P=.03) more than those receiving standard care. Although the
      intervention did not target depressed individuals or present material relating to
      mood management, those with probable depression (27% of the whole sample) showed
      clinically important improvements-a mean five-point change on the CESD short
      form. Participants who engaged more readily with the intervention were more
      likely to reduce their depression scores. A 1-year primary care based phone and
      Internet diet and exercise intervention can improve depressive symptoms in
      overweight women. Given the promise of phone and Internet-based interventions to
      improve both depression and lifestyle-related behaviors, and given that such
      interventions could extend the reach of primary care to many individuals at
      relatively low cost, these results suggest the need for further research,
      including the effects of additional mood management components.

PMID- 17557320
TI  - Intermittent parathyroid hormone (PTH) treatment and age-dependent effects on rat
      cancellous bone and mineral metabolism.
AB  - In recent years, intermittent PTH treatment has been investigated extensively for
      its efficacy in preventing osteoporotic fractures and to improve fracture healing
      and implant fixation. Although these tasks concern patients of all ages, very
      little is known about whether aging impacts the bone anabolic response to PTH.
      Female Sprague-Dawley rats of 1, 3, and 13 months of age were either treated by
      hPTH-(1-34) or by vehicle solution (CTR) for 1 week. As main outcome measures, we
      determined the effects on static and dynamic histomorphometry of cancellous bone.
      In addition, we measured gene expression in femur and serum parameters reflecting
      bone turnover and mineral metabolism. There was a profound decrease in bone
      formation rate (BFR) with aging in CTR rats, whereas PTH treatment resulted in a
      significant relative 1.5-, 3-, and 4.7-fold increase in BFR, without altering
      indices of bone resorption. Aging decreased and PTH increased mRNA levels for
      bone matrix proteins and growth factors in a gene-specific manner. In younger
      animals, PTH-induced a marked stimulation in the mineral apposition rate with no
      effect on osteoblast number, whereas the latter was increased in older animals
      (1.0-, 1.7-, and 3.1-fold). Treatment with PTH in young rats led to a significant
      increase in trabecular number (1.6-2.6/mm, p < 0.05), whereas older rats
      demonstrated increases in trabecular thickness only (52.8-77.8 microm, p <
      0.001). Although PTH increased bone formation at all ages, we found significant
      age-related differences in the cellular and molecular mechanisms involved in the
      bone anabolic response to the hormone.

PMID- 17557321
TI  - Knee instability after acute ACL rupture affects movement patterns during the mid
      stance phase of gait.
AB  - The purpose of this study was to identify gait asymmetries during the mid-stance
      phase of gait among subjects with knee instability ("non-copers") after acute
      anterior cruciate ligament (ACL) rupture. Twenty-one non-copers with acute,
      isolated ACL injury ambulated at their intentional walking speed as kinetic,
      kinematic, and electromyographic (EMG) data were collected bilaterally. Lower
      extremity movement patterns and muscle activity were analyzed during the mid
      stance and weight acceptance phases of stance. When compared to the uninjured
      limb, subjects exhibited lower sagittal plane knee excursions and peak knee
      angles, and higher muscle co-contraction on the injured limb. There was a lower
      knee flexion moment at peak knee extension, a trend for the knee contribution to
      the total support moment to be lower, and a higher ankle contribution to the
      total support moment on the injured limb. There were differences in the magnitude
      of muscle activity which included higher hamstring activity and lower soleus
      activity on the injured limb. Changes in quadriceps, soleus, and hamstring muscle
      activity on the injured limb were identified during weight acceptance that had
      not previously been reported, while hip compensation for a lower knee
      contribution to the total support moment has been described. Non-copers
      consistently stabilize their knee with a stiffening strategy involving less knee
      motion and higher muscle contraction. The variable combination of muscle
      adaptations that produce joint stiffness, and the ability of both the ankle and
      the hip to compensate for lower knee control indicate the non-coper neuromuscular
      system may be more malleable than previously believed.

PMID- 17557322
TI  - In vivo anterior tibial post contact after posterior stabilizing total knee
      arthroplasty.
AB  - Anterior polyethylene post failure in posterior stabilizing total knee
      arthroplasty (TKA) has been reported in recent patient follow-up studies.
      However, no data have been reported on the biomechanic interaction between the
      anterior tibial post and femoral component in posterior stabilizing TKA patients
      under physiological conditions. The objective of this study was to measure the in
      vivo anterior tibial post contact area at full knee extension using a dual
      orthogonal fluoroscopic imaging technique. Eleven osteoarthritic patients were
      investigated after posterior stabilizing TKA to measure the contact between the
      femoral component box and anterior aspect of the tibial post. Anterior tibial
      post contact, ranging between 0.5 and 80.9 mm(2), was detected in 63% of the
      healthy patients (seven out of the eleven patients) at weight-bearing full
      extension of the knee. The patients with anterior tibial post contact had
      significantly higher hyperextension angles (-8.4 +/- 4.3 degrees) than those
      without contact (1.4 +/- 7.2 degrees). A statistically significant difference was
      also detected in the femoral component flexion with respect to the femoral shaft
      between the patients with anterior post contact (2.7 +/- 2.7 degrees) and without
      anterior post contact (-1.3 +/- 2.2 degrees). These data indicated that anterior
      post contact did occur in hyperextension within posterior stabilizing TKA
      patients. While excessive anterior tibial post contact may cause polyethylene
      wear and potentially lead to post failure, the tibial post may also act as a
      substitute for the ACL at low flexion, thus providing stability to the joint
      after posterior stabilizing TKA.

PMID- 17557323
TI  - Generation of tendon-to-bone interface "enthesis" with use of recombinant BMP-2
      in a rabbit model.
AB  - The anatomical structure at bone-tendon and bone-ligament interfaces is called
      the enthesis. Histologically, the enthesis is characterized by a transitional
      series of tissue layers from the end of the tendon to bone, including tendon,
      fibrocartilage, calcified fibrocartilage, and bone. This arrangement yields
      stronger direct connection of the soft tissues to bone. In surgical repair, the
      enthesis has proven difficult to reproduce, and the success of ligament-bone
      bonding has depended on the fibrous attachment that forms after any ligament
      reconstructions. In this study, we attempted to generate a direct-insertion
      enthesis in two stages. First, recombinant human bone morphogenetic protein-2
      (rhBMP-2) was injected into the flexor digitorum communis tendon in the rabbit
      hind limb to induce ectopic ossicle formation. In a second step, the resultant
      tendon/ossicle complex was then surgically transferred onto the surface of the
      rabbit tibia to generate a stable tendon-bone junction. One month following
      surgery, histomorphological examination confirmed direct insertion of tendon-bone
      structures in the proximal tibia of the rabbit. Ultimate failure loads of the BMP
      2-generated tendon-bone junction were significantly higher than in the control
      group (p < 0.01). These findings suggest that it is possible to successfully
      regenerate a direct tendon-to-bone enthesis. Use of this approach may enable
      successful reconstruction of joints rendered unstable after ligamentous rupture
      or laxity after anterior cruciate ligament injury.

PMID- 17557324
TI  - Are disc pressure, stress, and osmolarity affected by intra- and extrafibrillar
      fluid exchange?
AB  - Because extrafibrillar water content dictates extrafibrillar osmolarity, we aimed
      to determine the influence of intra- and extrafibrillar fluid exchange on
      intradiscal pressures and stresses. As experimental results showed that
      extrafibrillar osmolarity affects intervertebral disc cell gene expression and
      crack propagation, quantification of the effects of changes in intra- and
      extrafibrillar fluid exchange is physiologically relevant. Therefore, our 3D
      osmoviscoelastic finite element (FE) model of the intervertebral disc was
      extended to include the intra- and extrafibrillar water differentiation. Two
      simulations were performed, one without intrafibrillar fluid and one with
      intrafibrillar fluid fraction as a function of the extrafibrillar osmotic
      pressure. The intrafibrillar fluid fraction as a function of the extrafibrillar
      osmotic pressure was exponentially fitted to human data and implemented into the
      model. Because of the low collagen content in the nucleus, no noticeable
      differences in intradiscal pressure estimation were observed. However, values of
      extrafibrillar osmolarity, hydrostatic pressure, and the total tissue stress
      calculated for the annulus were clearly different. Stresses, hydrostatic
      pressure, and osmolarity were underestimated when the intrafibrillar water value
      was neglected. As the loading increased, the discrepancies increased. In
      conclusion, the distribution of pressure and osmolarity in the disc is affected
      by intra- and extrafibrillar water exchange.

PMID- 17557325
TI  - Characteristics of sleep disturbances in Japanese patients with Parkinson's
      disease. A study using Parkinson's disease sleep scale.
AB  - The present multicenter cross-sectional study was performed using semistructured
      questionnaires to determine the contributing factors of sleep disturbances in
      Japanese patients with Parkinson's disease (PD). We used the Parkinson's disease
      sleep scale (PDSS, Japanese version). All data were obtained by means of
      interviewed questionnaire and physical examination by neurologists. The study was
      carried out between April 2005 and December 2005 at eight university hospitals
      and affiliated facilities in the Kanto area of Japan. A total of 188 (85 men and
      103 women) PD patients and 144 controls (64 men and 80 women) were included.
      Stepwise regression analysis identified complications of treatment, depression,
      age, and disease duration as significant risk factors of sleep disturbances in
      PD. Significant differences in total PDSS score were observed between Hoehn &
      Yahr (H&Y) Stages 1 and 4, between H&Y Stages 2 and 4, and between H&Y stages 3
      and 4 (Bonferroni test). The results of this survey suggested that complications
      due to treatment (dyskinesia, wearing off, on-off), depressive state, and disease
      stage are significant determinants of sleep disorders in Japanese patients with
      PD. We speculate that the reduction of neurotransmitters involved in the sleep
      wakefulness mechanism and degeneration of neurons progress together in parallel
      with deterioration of motor function.

PMID- 17557326
TI  - Crystal structure of ACE19, the collagen binding subdomain of Enterococus
      faecalis surface protein ACE.

PMID- 17557327
TI  - A tetrapeptide fragment-based design method results in highly stable artificial
      proteins.
AB  - Computational protein design has progressed rapidly over the last years. A number
      of design methods have been proposed and tested. In this paper, we report the
      successful application of a fragment-based method for protein design. The method
      uses statistical information on tetrapeptide backbone conformations. The
      previously published artificial fold of TOP 7 (Kuhlman et al., Science, 2003;
      302:1364-1368) was chosen as template. A series of polypeptide sequences were
      created that were predicted to fold into this target structure. Two of the
      designed proteins, M5 and M7, were expressed and characterized by fluorescence
      spectroscopy, circular dichroism and NMR. They showed the hallmarks of well
      ordered tertiary structure as well as cooperative folding/unfolding transitions.
      Furthermore, the two novel proteins were found to be highly stable against
      temperature and denaturant-induced unfolding.

PMID- 17557328
TI  - NAD+-dependent DNA ligase (Rv3014c) from Mycobacterium tuberculosis: novel
      structure-function relationship and identification of a specific inhibitor.
AB  - Mycobacterium tuberculosis codes for an essential NAD+-dependent DNA ligase
      (MtuLigA) which is a novel, validated, and attractive drug target. We created
      mutants of the enzyme by systematically deleting domains from the C-terminal end
      of the enzyme to probe for their functional roles in the DNA nick joining
      reaction. Deletion of just the BRCT domain from MtuLigA resulted in total loss of
      activity in in vitro assays. However, the mutant could form an AMP-ligase
      intermediate that suggests that the defects caused by deletion of the BRCT domain
      occur primarily at steps after enzyme adenylation. Furthermore, genetic
      complementation experiments using a LigA deficient E. coli strain demonstrates
      that the BRCT domain of MtuLigA is necessary for bacterial survival in contrast
      to E. coli and T. filiformis LigA, respectively. We also report the
      identification, through virtual screening, of a novel N-substituted tetracyclic
      indole that competes with NAD+ and inhibits the enzyme with IC50 in the low muM
      range. It exhibits approximately 15-fold better affinity for MtuLigA compared to
      human DNA ligase I. In vivo assays using LigA deficient S. typhimurium and E.
      coli strains suggest that the observed antibacterial activity of the inhibitor
      arises from specific inhibition of LigA over ATP ligases in the bacteria. In
      silico ligand-docking studies suggest that the exquisite specificity of the
      inhibitor arises on account of its mimicking the interactions of NAD+ with
      MtuLigA. An analysis of conserved water in the binding site of the enzyme
      suggests strategies for synthesis of improved inhibitors with better specificity
      and potency.

PMID- 17557329
TI  - Classification and functional annotation of eukaryotic protein kinases.
AB  - Reversible protein phosphorylation by protein kinases and phosphatases is a
      ubiquitous signaling mechanism in all eukaryotic cells. A multilevel hidden
      Markov model library is presented which is able to classify protein kinases into
      one of 12 families, with a misclassification rate of zero on the characterized
      kinomes of H. sapiens, M. musculus, D. melanogaster, C. elegans, S. cerevisiae,
      D. discoideum, and P. falciparum. The Library is shown to outperform BLASTP and a
      general Pfam hidden Markov model of the kinase catalytic domain in the retrieval
      and family-level classification of protein kinases. The application of the
      Library to the 38 unclassified kinases of yeast enriches the yeast kinome in
      protein kinases of the families AGC (5), CAMK (17), CMGC (4), and STE (1),
      thereby raising the family-level classification of yeast conventional protein
      kinases from 66.96 to 90.43%. The application of the Library to 21 eukaryotic
      genomes shows seven families (AGC, CAMK, CK1, CMGC, STE, PIKK, and RIO) to be
      present in all genomes analyzed, and so is likely to be essential to eukaryotes.
      Putative tyrosine kinases (TKs) are found in the plants A. thaliana (2), O.
      sativa ssp. Indica (6), and O. sativa ssp. Japonica (7), and in the amoeba E.
      histolytica (7). To our knowledge, TKs have not been predicted in plants before.
      This also suggests that a primitive set of TKs might have predated the radiation
      of eukaryotes. Putative tyrosine kinase-like kinases (TKLs) are found in the
      fungi C. neoformans (2), P. chrysosporium (4), in the Apicomplexans C. hominis
      (4), P. yoelii (4), and P. falciparum (6), the amoeba E. histolytica (109), and
      the alga T. pseudonana (6). TKLs are found to be abundant in plants (776 in A.
      thaliana, 1010 in O. sativa ssp. Indica, and 969 in O. sativa ssp. Japonica).
      TKLs might have predated the radiation of eukaryotes too and have been lost
      secondarily from some fungi. The application of the Library facilitates the
      annotation of kinomes and has provided novel insights on the early evolution and
      subsequent adaptations of the various protein kinase families in eukaryotes.

PMID- 17557330
TI  - Crystal structure of thioredoxin domain of ST2123 from thermophilic archaea
      Sulfolobus tokodaii strain7.

PMID- 17557331
TI  - Crystal structure of the PIN domain of human telomerase-associated protein EST1A.
AB  - Saccharomyces cerevisiae Est1p is a telomerase-associated protein essential for
      telomere length homeostasis. hEST1A is one of the three human Est1p homologues
      and is considered to be involved not only in regulation of telomere elongation or
      capping but also in nonsense-mediated degradation of RNA. hEST1A is composed of
      two conserved regions, Est1p homology and PIN (PilT N-terminus) domains. The
      present study shows the crystal structure of the PIN domain at 1.8 A resolution.
      The overall structure is composed of an alpha/beta fold or a core structure
      similar to the counterpart of 5' nucleases and an extended structure absent from
      archaeal PIN-domain proteins and 5' nucleases. The structural properties of the
      PIN domain indicate its putative active center consisting of invariant acidic
      amino acid residues, which is geometrically similar to the active center of 5'
      nucleases and an archaeal PAE2754 PIN-domain protein associated with exonuclease
      activity.

PMID- 17557332
TI  - A consensus algorithm to screen genomes for novel families of transmembrane beta
      barrel proteins.
AB  - The ability to search sequence datasets for membrane spanning proteins is an
      important requirement for genome annotation. However, the development of
      algorithms to identify novel types of transmembrane beta-barrel (TMB) protein has
      proven substantially harder than for transmembrane helical proteins, owing to a
      shorter TM domain in which only alternate residues are hydrophobic. Although
      recent reports have described important improvements in the development of such
      algorithms, there is still concern over their ability to confidently screen
      genomes. Here we describe a new algorithm combining composition and hidden Markov
      model topology based classifiers (called TMB-Hunt2), which achieves a
      crossvalidation accuracy of >95%, with 96.7% precision and 94.2% recall. An
      overview is given of the algorithm design, with a thorough assessment of
      performance and application to a number of genomes. Of particular note is that
      TMB/extracellular protein discrimination is significantly more difficult than
      TMB/cytoplasmic protein discrimination, with the predictor correctly rejecting
      just 74% of extracellular proteins, in comparison to 98% of cytoplasmic proteins.
      Focus is given to directions for further improvements in TMB/non-TMB protein
      discrimination, with a call for the development of standardized tests and
      assessments of such algorithms. Tools and datasets are made available through a
      website called TMB-Web (http://www.bioinformatics.leeds.ac.uk/TMB-Web/TMB-Hunt2).

PMID- 17557333
TI  - New classification of supersecondary structures of sandwich-like proteins
      uncovers strict patterns of strand assemblage.
AB  - To describe the supersecondary structure (SSS) of beta sandwich-like proteins
      (SPs), we introduce a structural unit called the "strandon." A strandon is
      defined as a set of sequentially consecutive strands connected by hydrogen bonds
      in 3D structures. Representing beta-proteins as the assembly of strandons exposes
      the underlying similarities in their SSS and enables us to construct a novel
      classification scheme of SPs. Classification of all known SPs is based on shared
      supersecondary structural features and is presented in the SSS database
      (http://binfs.umdnj.edu/sssdb/). Analysis of the SSS reveals two common specific
      patterns. The first pattern defines the arrangement of strandons and was found in
      95% of all examined SPs. The second pattern establishes the ordering of strands
      in the protein domain and was observed in 82% of the analyzed SPs. Knowledge of
      these two patterns that uncover the spatial arrangement of strands will likely
      prove useful in protein structure prediction.

PMID- 17557334
TI  - Structure, flexibility, and mechanism of the Bacillus stearothermophilus RecU
      Holliday junction resolvase.
AB  - Here we report a high resolution structure of RecU-Holliday junction resolvase
      from Bacillus stearothermophilus. The functional unit of RecU is a homodimer that
      contains a "mushroom" like structure with a rigid cap and two highly flexible
      loops extending outwards. These loops appear to be highly flexible/dynamic, and
      presumably are directly involved in DNA binding and holding it for catalysis.
      Structural modifications of both the protein and DNA upon their interaction are
      essential for catalysis. An Mg2+ ion is present in each of the two active sites
      in this homodimeric enzyme, and two water molecules are coordinated with each
      Mg2+ ion. Our data are consistent with one of these water molecules acting as a
      nucleophile and the other as a general acid. The identities of the general base
      and general acid involved in catalysis and the Lewis acid that stabilizes the
      pentacovalent transition state phosphate ion are proposed. A model for the RecU
      Holliday junction DNA complex is also proposed and discussed in the context of
      DNA binding and cleavage.

PMID- 17557335
TI  - Proteochemometric analysis of small cyclic peptides' interaction with wild-type
      and chimeric melanocortin receptors.
AB  - The melanocortin (MC) system confines unique G-protein coupled receptor pathways,
      which include the MC(1-5) receptors and their endogenous agonists and
      antagonists, the MCs and the agouti and agouti-related proteins. The MC4 receptor
      is an important target for development of drugs for treatment of obesity and
      cachexia. While natural MC peptides are selective for the MC1 receptor, some
      cyclic pentapeptides, such as the HS-129 peptide, show high selectivity for the
      MC4 receptor. Here we gained insight into the mechanisms for its recognition by
      MC receptors. To this end we correlated the interaction data of four HS peptide
      analogues with four wild-type and 14 multiple chimeric MC receptors to the binary
      and physicochemical descriptions of the studied entities by use of partial least
      squares regression, which resulted in highly valid proteochemometric models.
      Analysis of the models revealed that the recognition sites of the HS peptides are
      different from the earlier proteochemometrically mapped linear MSH peptides'
      recognitions sites, although they overlap partially. The analysis also revealed
      important amino acids that explain the selectivity of the HS-129 peptide for the
      MC4 receptor.

PMID- 17557336
TI  - Evaluation of docking programs for predicting binding of Golgi alpha-mannosidase
      II inhibitors: a comparison with crystallography.
AB  - Golgi alpha-mannosidase II (GMII), a zinc-dependent glycosyl hydrolase, is a
      promising target for drug development in anti-tumor therapies. Using X-ray
      crystallography, we have determined the structure of Drosophila melanogaster GMII
      (dGMII) complexed with three different inhibitors exhibiting IC50's ranging from
      80 to 1000 microM. These structures, along with those of seven other available
      dGMII/inhibitor complexes, were then used as a basis for the evaluation of seven
      docking programs (GOLD, Glide, FlexX, AutoDock, eHiTS, LigandFit, and FITTED). We
      found that small inhibitors could be accurately docked by most of the software,
      while docking of larger compounds (i.e., those with extended aromatic cycles or
      long aliphatic chains) was more problematic. Overall, Glide provided the best
      docking results, with the most accurately predicted binding around the active
      site zinc atom. Further evaluation of Glide's performance revealed its ability to
      extract active compounds from a benchmark library of decoys.

PMID- 17557337
TI  - Clinical correlates of mitochondrial function in Huntington's disease muscle.
AB  - Huntington's disease (HD) is caused by an abnormally expanded CAG repeat in the
      IT-15 gene, which encodes a widely expressed protein called huntingtin.
      Abnormalities of mitochondrial respiratory chain function, specifically complex
      II/III, have been identified in HD striatum and defects of energy metabolism have
      been demonstrated in vivo in skeletal muscle in both symptomatic and
      presymptomatic HD patients. We have investigated respiratory chain function using
      histochemical and biochemical methods in HD skeletal muscle from 12 patients and
      compared these with 12 age and sex-matched controls. The data from the HD
      patients were related to clinical parameters of HD including the Unified
      Huntington's Disease Rating Scale (UHDRS). There were positive correlations
      between CAG repeat years (a product of CAG repeat length and age) and both motor
      (P < 0.002) and cognitive (P < 0.01) scores of the UHDRS. There was no
      significant difference in the activities of complexes I to IV compared to age
      matched controls. However, there were significant correlations for individual HD
      complex II/III activities with disease duration (P = 0.017), repeat years (P =
      0.032), and cognitive scores (P = 0.019). There was also evidence from
      ultrastructural studies that inclusion formation may occur in HD muscle. These
      results provide additional evidence that mutant huntingtin influences
      mitochondrial complex II/III function in non-neuronal tissue (skeletal muscle)
      and suggest that muscle may be a potential marker of disease progression in HD.

PMID- 17557338
TI  - In vitro and in vivo optimization of impaction allografting by demineralization
      and addition of rh-OP-1.
AB  - Impaction allografting is a bone tissue engineering technique currently used in
      lower limb reconstruction orthopedic surgery. Our hypothesis was that biological
      optimization can be achieved by demineralization and addition of osteogenic
      protein-1 (OP-1) to the allograft. The objective of our in vitro study was to
      evaluate human mesenchymal stem cell (MSC) proliferation (Alamar Blue assay,
      titrated thymidine assay, total DNA Hoechst 33258, and scanning electron
      microscopy) and osteogenic differentiation (alkaline phosphatase assay) in two
      types of impacted carrier, namely, demineralized bone matrix (DBM) and insoluble
      collagenous bone matrix (ICBM), with or without OP-1. The objective in vivo was
      to compare the osteogenic potential of impacted DBM with or without OP-1, with
      that of impacted fresh frozen allograft (FFA), again with or without OP-1. DBM +
      OP-1 optimized osteoinduction and significantly improved (p < 0.05) proliferation
      and differentiation in comparison to the majority of all other graft preparation
      in vitro. In addition, DBM + OP-1 was significantly superior, with regard to
      osteogenesis, compared to the impacted FFA alone (p < 0.001), FFA + OP-1 (p =
      0.01) and DBM alone (p = 0.02) in vivo. We propose that partial demineralization
      and addition of OP-1 provides a good method for improving the osteoinductive
      properties of fresh allograft currently used in the impaction grafting technique.

PMID- 17557339
TI  - Nonpharmacological treatment, fludrocortisone, and domperidone for orthostatic
      hypotension in Parkinson's disease.
AB  - There is limited evidence for the treatment of orthostatic hypotension in
      idiopathic Parkinson's disease. The objective of this study was to determine the
      efficacy of three treatments (nonpharmacological therapy, fludrocortisone, and
      domperidone). Phase I assessed the compliance, safety, and efficacy of
      nonpharmacological measures. Phase II was a double-blind randomized controlled
      crossover trial of the two medications. Primary outcome measures consisted of the
      orthostatic domain of the Composite Autonomic Symptom Scale (COMPASS-OD), a
      clinical global impression of change (CGI), and postural blood pressure testing
      via bedside sphygmomanometry (Phase I) or tilt table testing (Phase II). For the
      17 patients studied, nonpharmacological therapy did not significantly alter any
      outcome measure. Both medications improved the CGI and COMPASS-OD scores. There
      was a trend towards reduced blood pressure drop on tilt table testing, with
      domperidone having a greater effect.

PMID- 17557341
TI  - Olfaction testing in PD: risky conclusions.

PMID- 17557342
TI  - Genetics of restless legs syndrome (RLS): State-of-the-art and future directions.
AB  - Several studies demonstrated that 60% of restless legs syndrome (RLS) patients
      have a positive family history and it has been suggested that RLS is a highly
      hereditary trait. To date, several loci have been mapped but no gene has been
      identified yet. Phenocopies and possible nonpenetrants made it difficult to
      detect a common segregating haplotype within the families. Defining the exact
      candidate region is hampered by possible intrafamilial, allelic, and nonallelic
      heterogeneity. One important prerequisite for future successful genetic studies
      in RLS is the availability of large and thoroughly phenotyped patients and family
      samples for linkage as well as association studies.

PMID- 17557343
TI  - Motor cortex stimulation for levodopa-resistant akinesia: case report.
AB  - We treated a patient with levodopa-resistant akinesia with motor cortex
      stimulation (MCS), and she showed dramatic improvement more than 1 year. On
      admission, the patient presented severe akinesia and gait disturbance without
      tremor and rigidity, and did not respond to levodopa test. The patient was
      suspected pure akinesia and progressive supranuclear palsy. First, high-frequency
      rTMS of primary motor cortex was examined, and showed the dramatic improvement.
      Next, chronic subdural electrodes were implanted over the motor cortex
      bilaterally. One year after surgery, the Unified Parkinson's Disease Rating Scale
      had improved remarkably, and she could walk four times faster than before. The H2
      15O PET study showed a significant increase of rCBF in the left SMA and right
      dorsolateral prefrontal cortex after bilateral MCS. MCS may be an alternative
      treatment for patients with akinesia, including those with PD, and particularly
      for levodopa-resistant patients, who respond well to rTMS.

PMID- 17557344
TI  - Is PD-MCI a useful concept?

PMID- 17557345
TI  - RLS epidemiology--frequencies, risk factors and methods in population studies.
AB  - Since the introduction of the four minimal criteria for restless legs syndrome
      (RLS) in 1995 by the International Restless Legs Syndrome Study Group, the number
      of published studies in RLS during the past 10 years has substantially increased.
      These studies improved our knowledge about prevalences, risk factors or outcomes
      of the disease at the population level and provided hypothesis about potential
      biological mechanism. This article reviews the existing studies on the prevalence
      and risk factors of RLS and critically describes existing methodological problems
      in the assessment of the disease in epidemiologic studies.

PMID- 17557346
TI  - Role of fibroblasts and fibroblast-derived growth factors in periprosthetic
      angiogenesis.
AB  - The periprosthetic granulomatous soft tissue [designated iterfacial membrane
      (IFM) in this study] exhibits heterogeneous histopathological features, in which
      highly vascularized areas with dense cellularity alternate with fibrotic and
      pseudocapsule-like tissue structures. Although macrophage/monocyte activation is
      a prominent event in the periprosthetic environment, fibroblasts also phagocytose
      particulate wear debris both in vivo and in vitro. Particulate wear debris and/or
      cytokines/growth factors alone or in combination (e.g., in conditioned media of
      explant cultures of IFMs) stimulated normal synovial and IFM fibroblasts to
      express inflammatory mediators and growth factors such as interleukin (IL)-1beta,
      IL-6, IL-8, three isoforms of vascular endothelial growth factor (VEGF),
      monocyte/macrophage chemoattractant protein-1 (MCP-1), macrophage-colony
      stimulating factor (M-CSF), cycloxygenases (Cox-1 and Cox-2), acid- and basic
      fibroblast growth factors (FGF-1 and FGF-2), leukemia inhibitory factor-1 (LIF
      1), transforming growth factor beta-1 (TGF-beta1), receptor activator of nuclear
      factor-kappa B ligand (RANKL), and osteoprotegerin (OPG). Thus, the fibroblast is
      capable of expressing a wide array of angiogenic and osteoclastogenic factors
      which are involved in the detrimental processes of the periprosthetic osteolysis.

PMID- 17557348
TI  - Postoperative serum attenuates LPS-induced release of TNF-alpha in orthopaedic
      surgery.
AB  - Studies with ex vivo stimulation of whole blood samples from injured patients
      have revealed a diminished production capacity for a broad range of secretory
      products, including inflammatory cytokines. Recent interest has focused on the
      release of mediators in serum that depress the cell-mediated immune response
      following trauma. The involvement of the lipid mediator prostaglandin E2 (PGE2)
      has been assumed because it is a potent endogenous immunosuppressor. In the
      present study, we tested the hypothesis that inhibitory substances circulating in
      the patient's serum after a major musculoskeletal trauma might impair leukocyte
      function by evaluating the effect of such serum on cytokine release in a whole
      blood model. Six females and three males undergoing elective total hip
      replacement were included in the study. Ex vivo LPS-induced TNF-alpha and IL-10
      were measured in whole blood sampled preoperatively and added serum taken before,
      at the end of operation, and at postoperative days 1 and 6 with saline as
      negative control. LPS induced significant releases of TNF-alpha and IL-10 in
      whole blood. Addition of preoperative, postoperative, and day-1 postoperative
      serum did not alter the LPS-induced release of TNF-alpha as compared to saline.
      In the presence of serum from postoperative day 6, however, the expression of TNF
      alpha was significantly reduced as compared to saline and preoperative serum (p =
      0.021 and 0.008, respectively). Neither of the serum samples altered the release
      of IL-10. PGE2 was significantly (p = 0.008) increased in serum at postoperative
      day 6 as compared to preoperative levels. In conclusion, these data show that at
      day 6 after major orthopaedic surgery, the patient serum contained activity that
      inhibited ex vivo LPS-induced TNF-alpha release. The potent TNF-alpha inhibitory
      activity found at day 6 after injury correlated with increased levels of PGE2 and
      indicates cell-mediated hyporesponsiveness to a second stimulus.

PMID- 17557349
TI  - Sumatriptan for prevention of acute mountain sickness: randomized clinical trial.
AB  - OBJECTIVE: To determine the impact of sumatriptan prophylaxis on acute mountain
      sickness (AMS) and altitude headache development within 24 hours of ascent, we
      designed a double-blind, randomized, clinical trial. METHODS: A prospective,
      double-blind, randomized, placebo-controlled trial was conducted in Tochal
      Mountain Hotel at an altitude of 3,500 meters above sea level during October 2006
      to November 2006. A total of 102 Iranian adults were assigned to receive either
      sumatriptan succinate (50mg) or placebo within 1 hour of ascent. AMS incidence
      was measured by Lake Louise AMS score > or = 3 with headache and one other
      symptom. Secondary outcome measures included severity of syndrome (Lake Louise
      scores > or = 5), incidence of headache, and severity of headache. RESULTS: Based
      on intention-to-treat analysis, AMS was more prevalent in placebo group (n = 23
      [45.1%]) than sumatriptan group (n = 12 [23.5%]; p = 0.02). Headache also had a
      greater rate for placebo users (placebo vs sumatriptan group: 29 [56.9%] vs 17
      [33.3%]; p = 0.02). No association was detected between sumatriptan prophylaxis
      and AMS or altitude headache severity. DISCUSSION: Sumatriptan prophylaxis is
      effective to prevent AMS development. Furthermore, our findings confirm cerebral
      vasodilative and edematous mechanisms of AMS progression, whereas sumatriptan is
      a selective 5-hydroxytryptamine(1) receptor subtype agonist and a selective
      cerebral vasoconstrictor as a result (http://www.controlled
      trials.com/ISRCTN87201238/).

PMID- 17557351
TI  - Alzheimer's disease and essential tremor finally meet.

PMID- 17557350
TI  - Congenital lymphocytic choriomeningitis virus infection: spectrum of disease.
AB  - OBJECTIVE: Lymphocytic choriomeningitis virus (LCMV) is a human pathogen and an
      emerging neuroteratogen. When the infection occurs during pregnancy, the virus
      can target and damage the fetal brain and retina. We examined the spectrum of
      clinical presentations, neuroimaging findings, and clinical outcomes of children
      with congenital LCMV infection. METHODS: Twenty children with serologically
      confirmed congenital LCMV infection were identified. The children underwent
      neuroimaging studies and were followed prospectively for up to 11 years. RESULTS:
      All children with congenital LCMV infection had chorioretinitis and structural
      brain anomalies. However, the presenting clinical signs, severity of vision
      disturbance, nature and location of neuropathology, and character and severity of
      brain dysfunction varied substantially among cases. Neuroimaging abnormalities
      included microencephaly, periventricular calcifications, ventriculomegaly,
      pachygyria, cerebellar hypoplasia, porencephalic cysts, periventricular cysts,
      and hydrocephalus. The combination of microencephaly and periventricular
      calcifications was the most common neuroimaging abnormality, and all children
      with this combination had profound mental retardation, epilepsy, and cerebral
      palsy. However, others had less severe neuroimaging abnormalities and better
      outcomes. Some children had isolated cerebellar hypoplasia, with jitteriness as
      their presenting sign and ataxia as their principal long-term neurological
      dysfunction. INTERPRETATION: Congenital LCMV infection can have diverse
      presenting signs, neuroimaging abnormalities, and clinical outcomes. In the
      companion article to this study, we utilize an animal model to show that the
      clinical and pathological diversity in congenital LCMV infection is likely due to
      differences in the gestational timing of infection.

PMID- 17557352
TI  - Niaspan increases angiogenesis and improves functional recovery after stroke.
AB  - OBJECTIVE: High-density lipoprotein (HDL) is implicated in the modulation of
      angiogenesis. In this study, we investigated whether the Niacin-mediated increase
      of HDL regulates angiogenesis and thereby improves functional outcome after
      stroke. METHODS: Adult male rats were subjected to middle cerebral artery
      occlusion and were treated with or without different doses (40 and 80 mg/kg) of
      Niaspan, starting 24 hours after middle cerebral artery occlusion and daily for
      14 days. Neurological functional tests were performed, and serum HDL level was
      measured. Angiogenesis and angiogenic factor expression were measured by
      immunohistochemistry, corneal neovascularization and capillary tube formation
      assay, and Western blot, respectively. RESULTS: Niaspan significantly increased
      HDL level, promoted angiogenesis in the ischemic brain, and improved functional
      outcome after stroke. Niaspan also significantly increased corneal
      neovascularization compared with nontreatment control. Mechanisms underlying the
      Niaspan-induced vascular remodeling were investigated. Niaspan increased the
      expression of vascular endothelial growth factor and angiopoietin-1 (Ang1), and
      phosphorylation of Akt, endothelial nitric oxide synthase (NOS), and Tie2 in the
      ischemic brain. Niacin upregulated Ang1 expression in cultured brain endothelial
      cells and increased vascular endothelial growth factor, Ang1, and endothelial NOS
      expression in cultured astrocytes, and dose-dependently increased capillary tube
      formation compared with nontreatment control. Inhibition of NOS partially
      decreased Niacin-induced capillary tube formation. Inhibition of phosphoinositide
      3-kinase or knockdown of Tie2 substantially and significantly decreased Niacin
      induced capillary tube formation. INTERPRETATION: Niacin increases HDL and
      promotes angiogenesis, which may contribute to improvement of functional outcome
      after stroke. The Ang1/Tie2, phosphoinositide 3-kinase/Akt, and endothelial NOS
      pathways appear to mediate Niacin-induced angiogenesis.

PMID- 17557353
TI  - An open trial of levetiracetam for segmental and generalized dystonia.
AB  - Local botulinum toxin injections represent the treatment of choice for most
      patients with focal dystonia. However, patients with segmental or generalized
      forms require additional pharmacologic treatment which is often ineffective or
      limited by intolerable side-effects. An animal study and three case reports
      suggested antidystonic effects of levetiracetam, a pyrrolidone derivate, whereas
      a recent open-label study found no improvement in 10 patients with primary
      idiopathic cervical dystonia. We studied the efficacy of levetiracetam in a daily
      dose of 3000 mg in 10 consecutive patients with otherwise therapy refractory
      segmental or generalized dystonia. At 4-week follow-up, none of the patients
      showed improvement of dystonia, mild side-effects were observed in 3 patients.

PMID- 17557354
TI  - Serum cholesterol, use of lipid-lowering drugs, and risk of Parkinson disease.

PMID- 17557355
TI  - Effects of chronic subthalamic stimulation on nonmotor fluctuations in
      Parkinson's disease.
AB  - The aim of this study was to assess the outcome of nonmotor fluctuations (NMF)
      after chronic Subthalamic nucleus (STN) Deep Brain Stimulation (DBS) in
      Parkinson's disease(PD). Chronic stimulation of the STN has proved to be an
      effective treatment for advanced PD with motor complications. The outcome of NMF,
      which are also disabling, remains unknown. Forty-patients underwent bilateral STN
      stimulation. Each patient was interviewed before and after 1 yr of STN DBS with a
      structured questionnaire about their NMF. After 1 yr of chronic stimulation, the
      improvement in the motor score (UPDRS III) and dyskinesia amounted respectively
      to 67.4 and 76.3%. The decrease in motor fluctuations (MF) was 59% and 13
      patients reported that their MF had disappeared. Comparatively, a reduction of
      the total number of NMF was also observed (mean number preoperatively: 15.6 per
      patient, postoperatively: 6.6). Most of the nonmotor fluctuating symptoms
      occurred in the "off" state preoperatively and no longer depended on the
      patient's motor state after surgery. The improvement in NMF was not identical for
      the different categories: pain/sensory fluctuations showed the best response to
      STN DBS (84.2%). Dysautonomic and cognitive fluctuations were also markedly
      improved (>60%) while psychic fluctuations remained the most frequent
      postoperative NMF observed. Some incapacitating manifestations such as drenching
      sweats and akathisia showed a remarkably good response to STN stimulation. In
      conclusion STN DBS alleviates NMF. It has strikingly successful effects on
      sensory, dysautonomic and cognitive fluctuations. However, psychic fluctuations
      respond less consistently to this treatment.

PMID- 17557356
TI  - Dopaminergic modulation of timing control and variability in the gait of
      Parkinson's disease.
AB  - The basal ganglia have been implicated in timing control, yet the nature of
      timing disturbances in Parkinson's disease (PD) is poorly understood. We
      evaluated the influence of timing cues on spatiotemporal aspects of gait control
      and its variability, and the impact of dopaminergic treatment on timing. Three
      separate groups: 19 PD (OFF state); 24 PD (ON state); and 30 control participants
      were tested. Participants walked on a computerized carpet at four randomized and
      metronome-controlled rates: self-paced, 60, 80, or 100 steps/min. To our
      knowledge, this is the first study to demonstrate that medicated PD patients had
      poorer timing control than patients withdrawn from medication and healthy
      participants when modulating timing to an external stimulus. Increased step-to
      step timing variability and deficits in mean temporal gait characteristics
      revealed that the medicated PD group (in contrast to nonmedicated PD group)
      performed least like healthy participants. This was observable in externally-cued
      conditions, but not during self-paced gait. Similar to previous research, step
      length contributed to overall slowness in PD, while temporal characteristics of
      gait did not. Interestingly, healthy participants increased stride length with
      each increase in cue rate, whereas both PD groups locked their step length
      regardless of temporal demand. Step-to-step variability differences between PD
      and healthy (e.g. step and double-support time measurements) may be indicative of
      specific basal ganglia involvement in temporal control of gait.

PMID- 17557357
TI  - Analysis of plasma protein adsorption onto PEGylated nanoparticles by
      complementary methods: 2-DE, CE and Protein Lab-on-chip system.
AB  - The biodistribution of colloidal carriers after their administration in vivo
      depends on the adsorption of some plasma proteins and apolipoproteins on their
      surface. Poly(methoxypolyethyleneglycol cyanoacrylate-co-hexadecylcyanoacrylate)
      (PEG-PHDCA) nanoparticles have demonstrated their capacity to cross the blood
      brain barrier (BBB) by a mechanism of endocytosis. In order to clarify this
      mechanism at the molecular level, proteins and especially apolipoproteins
      adsorbed at the surface of PEG-PHDCA nanoparticles were analyzed by complementary
      methods such as CE and Protein Lab-on-chip in comparison with 2-D PAGE as a
      method of reference. Thus, the ability of those methodologies to identify and
      quantify human and rat plasma protein adsorption onto PEG-PHDCA nanoparticles and
      conventional PHDCA nanoparticles was evaluated. The lower adsorption of proteins
      onto PEG-PHDCA nanoparticles comparatively to PHDCA nanoparticles was evidenced
      by 2-D PAGE and Protein Lab-on-chip methods. CE allowed the quantification of
      adsorbed proteins without the requirement of a desorption procedure but failed,
      in this context, to analyze complex mixtures of proteins. The Protein Lab-on-chip
      method appeared to be very useful to follow the kinetic of protein adsorption
      from serum onto nanoparticles; it was complementary to 2-D PAGE which allowed the
      identification (with a relative quantification) of the adsorbed proteins. The
      overall results suggest the implication of the apolipoprotein E in the mechanism
      of passage of PEG-PHDCA nanoparticles through the BBB.

PMID- 17557358
TI  - Determination of 1-methylhistidine and 3-methylhistidine by capillary and chip
      electrophoresis with contactless conductivity detection.
AB  - CE with capacitively coupled contactless detection (C4D) was used to determine 3
      methylhistidine (3-MH) and 1-methylhistidine (1-MH). The C4D response to 3-MH was
      studied in a BGE consisting of 500 mM acetic acid and ammonia at varying
      concentration and the results were compared with the theory. Complete separation
      of a model mixture of 3-MH, 1-MH, and histidine (His) was attained in two
      optimized BGEs, one containing 500 mM HAc, 20 mM NH4OH, and 0.1 % m/v
      hydroxyethylcellulose (HEC), pH 3.4 (I) and the other consisting of 100 mM
      morpholinoethanesulfonic acid (MES), 25 mM LiOH, and 0.1 % m/v HEC, pH 5.5 (II).
      These optimized BGEs were tested in CE/C4D analyses of urine. Promising results
      were obtained for separation and determination of 3-MH, 1-MH, and His on a
      silicon microchip, using aluminum strips as the C4D electrodes; the three
      analytes were baseline-separated within less than 30 s with a separation channel
      effective length of 38 mm. The LOD were satisfactory and amounted to 26.4 microM
      for 3-MH and 18.3 microM for 1-MH.

PMID- 17557359
TI  - Probing the stability of serum protein-ruthenium(III) drug adducts in the
      presence of extracellular reductants using CE.
AB  - A CE kinetic assay was developed to study the stability of the adducts of a novel
      ruthenium(III)-based anticancer agent with serum proteins under simulated
      reductive physiological conditions. Formation of the reactive Ru(II) species and
      their release from the serum proteins are thought to play an important role in
      the mode-of-action of indazolium trans-[tetrachlorobis(1H
      indazole)ruthenate(III)] (KP1019) which has successfully finished a clinical
      phase I study. The CE method was adapted, in zone electrophoresis and affinity CE
      modes, to make obvious that such transformation would take place in the hypoxic
      tumor tissue rather than in the bloodstream. Indeed, no measurable effect of
      extracellular concentration levels of glutathione incorporated into the BGE on
      the UV signals of albumin and transferrin adducts was observed over 30 min of
      examination. Incubation of the KP1019-albumin adduct with the major blood
      reducing agent, ascorbic acid, revealed no changes in the continuously monitored
      peak areas (average corrected responses were 9.56 +/- 0.86 and 9.87 +/- 0.60 mAU
      for the adduct and its mixtures with ascorbic acid in the physiological range of
      1 x 10(-5) -8 x 10(-5) M, respectively). On the other hand, both the transferrin
      adduct and transferrin itself accelerated the oxidation of ascorbic acid;
      however, the oxidation rate constants measured by CE were virtually the same:
      (19.1 +/- 4.4) x 10(-3) and (18.2 +/- 5.0) x 10(-3) min(-1), respectively. In
      order to confirm more unambiguously the stability of KP1019-protein adducts in
      the presence of ascorbic acid (UV absorbance detection does not distinguish the
      adduct and protein signals), CE with inductively coupled plasma (ICP) MS
      detection was applied to follow metal-selectively the signal of bound ruthenium,
      which remained unaffected by this reducing agent. This work appears the first to
      present the application of CE to the stability studies of the protein-bound
      metallodrugs.

PMID- 17557360
TI  - CE separation of proteins and yeasts dynamically modified by PEG pyrenebutanoate
      with fluorescence detection.
AB  - The optimized protocols of the bioanalytes separation, proteins and yeasts,
      dynamically modified by the nonionogenic tenside PEG pyrenebutanoate, were
      applied in CZE and CIEF with the acidic gradient in pH range 2-5.5, both with
      fluorescence detection. PEG pyrenebutanoate was used as a buffer additive for a
      dynamic modification of proteins and/or yeast samples. The narrow peaks of
      modified analytes were detected. The values of the pI's of the labeled proteins
      were calculated using new fluorescent pI markers in CIEF and they were found to
      be comparable with pI's of the native compounds. As an example of the possible
      use of the suggested CIEF technique, the mixed cultures of yeasts, Candida
      albicans, Candida glabrata, Candida kefyr, Candida krusei, Candida lusitaniae,
      Candida parapsilosis, Candida tropicalis, Candida zeylanoides, Geotrichum
      candidum, Saccharomyces cerevisiae, Trichosporon asahii and Yarrowia lipolytica,
      were reproducibly focused and separated with high sensitivity. Using UV
      excitation for the on-column fluorometric detection, the minimum detectable
      amounts of analytes, femtograms of proteins and down to ten cells injected on the
      separation capillary, were estimated.

PMID- 17557361
TI  - Ion-interaction CZE: the presence of high concentrations of ion-pairing reagents
      demonstrates the complex mechanisms involved in peptide separations.
AB  - We have furthered our understanding of the separative mechanism of a novel CE
      approach, termed ion-interaction CZE (II-CZE), developed in our laboratory for
      the resolution of mixtures of cationic peptides. Thus, II-CZE and RP-HPLC were
      applied to the separation of peptides differing by a single amino acid
      substitution in 10- and 12-residue synthetic model peptide sequences.
      Substitutions differed by a wide range of properties or side-chain type (e.g.,
      alkyl side-chains, polar side-chains, etc.) at the substitution site. When
      carried out in high concentrations (400 mM) of pentafluoropropionic acid (PFPA),
      II-CZE separated peptides in order of increasing hydrophobicity when the
      substituted side-chains were of a similar type; when II-CZE was applied to the
      mixtures of peptides with substitutions of side-chains that differed in the type
      of functional group, there was no longer a correlation of electrophoretic
      mobility in II-CZE with relative peptide hydrophobicity, suggesting that a third
      factor is involved in the separative mechanism beyond charge and hydrophobicity.
      Interestingly, the hydrophobic PFPA- anion is best for separating peptides that
      differ in hydrophobicity with hydrophobic side-chains but high concentrations of
      the hydrophilic H2PO4- anion are best when separating peptides that differ in
      polar side-chains relative to hydrophobic side-chains. We speculate that
      differential hydration/dehydration properties of various side-chains in the
      peptide and the hydration/dehydration properties of the hydrophilic/hydrophobic
      anions as well as the electrostatic attractions between the peptide and the
      anions in solution all play a critical role in these solution-based effects.

PMID- 17557362
TI  - Determination of binding constants of vasoactive intestinal peptide to
      poly(amidoamine) dendrimers designed for drug delivery using ACE.
AB  - The purpose of the present paper was to study at physiological pH the affinity
      between vasoactive intestinal peptide (VIP) and four poly(amidoamine) dendrimers
      (PAMAMs) designed for drug delivery. Therefore, a fast and reproducible CE method
      was first developed to analyze the strongly basic peptide. To allow an accurate
      determination of binding constant (K) values, the ability to suppress peptide
      adsorption onto the silica capillary of nonpermanent coatings (poly(ethylene
      oxide) (PEO), low and medium relative molecular masses
      poly(diallyldimethylammonium chloride) (PDDA)) or poly(acrylamide) permanent
      coating (PAA) was evaluated. Very good intraday repeatability of VIP migration
      times and peak areas (0.1-0.6 and 2.9-4.9% RSD, respectively) was obtained using
      two of the investigated coatings (PEO and PDDA with medium molecular mass). ACE
      combined with these dynamic coatings was then employed to evaluate K between VIP
      and two amine-terminated PAMAM dendrimers of generation 2 and 5 (G2.NH2, G5.NH2)
      and two carboxyl-terminated PAMAM derivatives of generation 2 and 5 (G2.COOH,
      G5.COOH). Binding constant of (6.7 +/- 1.1) x 10(4)/M could be determined for the
      couple VIP/G5.NH2, while no affinity was evidenced between VIP and all other
      dendrimers investigated. These results suggest that G5.NH2 might be an
      interesting carrier for the delivery of VIP.

PMID- 17557363
TI  - Quantitative measurement of spinal cord blood volume in humans using vascular
      space-occupancy MRI.
AB  - Although perfusion is of major interest for many spinal cord disorders, there is
      no established, reproducible technique for evaluating blood flow or blood volume
      of the spinal cord in humans. Here the first report of in vivo measurement of
      human spinal cord blood volume (scBV) is presented. An FDA-approved contrast
      agent, Gd-DTPA, was used as an intravascular agent for the cord parenchyma, and
      pre-/post-contrast vascular-space-occupancy (VASO) MRI experiments were performed
      to obtain a quantitative estimation of scBV in mL blood/100 mL tissue. VASO MRI
      was used because it does not rely on knowledge of an arterial input function, it
      avoids the imaging artifacts of single-shot echo planar imaging approaches, and
      it requires only relatively simple and direct calculations for scBV
      quantification. Preliminary tests at 1.5 T and 3 T gave mean +/- SD scBV values
      of 4.3 +/- 0.7 ml/100 mL tissue (n = 6) and 4.4 +/- 0.7 ml/100 mL tissue (n = 4),
      respectively, consistent with the expectation that the scBV values would not be
      field-dependent.

PMID- 17557364
TI  - The Biflow: an instrument for transfer-loop mediated, continuous, preparative
      scale isoelectric trapping separations.
AB  - The Biflow, a new isoelectric trapping instrument was designed to obtain a narrow
      DeltapI fraction from a complex feed in one step. The Biflow contains two
      identical separation units, each unit houses: an anode and cathode compartment,
      an anodic and cathodic membrane, an anodic and cathodic separation compartment,
      and a separation membrane. The separation units are connected to independent
      power supplies. The anodic membranes in Units 1 and 2 typically buffer at the
      same pH value and so do the cathodic membranes. The separation membranes in Units
      1 and 2 buffer at different pH values, these determine the pI range (DeltapI) of
      the product. The cathodic separation compartments in Units 1 and 2 contain the
      feed and harvest streams. The two anodic separation compartments, connected
      through an electrically insulating air gap, form the transfer loop through which
      the transfer stream is recirculated between Units 1 and 2. Ampholytic components
      in the feed, with pI values lower than the pH of the buffering membrane in Unit
      1, pass into the transfer stream and are shuttled into Unit 2. In Unit 2,
      components in the transfer stream which have pI values higher than the pH of the
      buffering membrane in Unit 2, pass into the harvest stream. This double transfer
      of the target component, oppositely directed, guarantees the complete exclusion
      of products outside the desired DeltapI range from the harvest stream. The
      utility of the Biflow unit was demonstrated by isolating carnosine from a mixture
      of UV-absorbing ampholytes and ovalbumin isoforms as well as 4.4 <pI <4.5 and 5.4
      <pI <5.5 minor constituents from chicken egg white.

PMID- 17557365
TI  - Theory and practical understanding of the migration behavior of proteins and
      peptides in CE and related techniques.
AB  - CEC is defined as an analytical method, where the analytes are separated on a
      chromatographic column in the presence of an applied voltage. The separation of
      charged analytes in CEC is complex, since chromatographic interaction,
      electroosmosis and electrophoresis contribute to the experimentally observed
      behavior. The putative contribution of effects such as surface electrodiffusion
      has been suggested. A sound theoretical treatment incorporating all effects is
      currently not available. The question of whether the different effects contribute
      in an independent or an interdependent manner is still under discussion. In this
      contribution, the state-of-the-art in the theoretical description of the
      individual contributions as well as models for the retention behavior and in
      particular possible dimensionless 'retention factors' is discussed, together with
      the experimental database for the separation of charged analytes, in particular
      proteins and peptides, by CEC and related techniques.

PMID- 17557366
TI  - Autofocusing and ESI-MS analysis of protein digests in a miniaturized
      multicompartment electrolyzer.
AB  - Free-solution IEF of protein digests was studied in a newly introduced
      MicroRotofortrade mark multicompartment electrolyzer. The fractionation was
      performed in a cylindrical separation chamber divided into ten compartments with
      or without the addition of carrier ampholytes. In the case of autofocusing mode
      of operation, the tryptic digest itself served as the mixture of ampholytes
      leading to the separation of the peptides with well-defined pI's. The focusing
      process was monitored visually using colored pI markers. The resulting fractions
      from both modes of the separation were analyzed by CE and electrospray-TOF mass
      spectrometer using electrospray tips microfabricated in polyimide. Additional
      experiments, aiming at visualization of the mass flux within the focusing
      compartments were performed using isotachophoretic migration of color cationic
      tracers. The study considered the autofocusing of both the peptides with well
      defined narrow pI's as well as those showing negligible net charge in a broader
      pH range. Although not all peptides in the protein digests have well-defined pI's
      the autofocusing process can preseparate many of them leading to higher S/N in
      the ESI-MS signals and improved protein sequence coverage.

PMID- 17557367
TI  - Repeatability of chemical cytometry: 2-DE analysis of single RAW 264.7 macrophage
      cells.
AB  - This report presents the use of 2-DE with ultrasensitive fluorescence detection
      as a chemical cytometry tool to characterize the protein and biogenic amine
      content of single cells from the RAW 264.7 murine macrophage cell line. Cells
      were sorted by cell cycle prior to 2-DE analysis. Cells in the G2/M phase of the
      cell cycle were aspirated into the first-dimensional capillary and lysed. The
      cellular contents were fluorescently labeled and first separated by capillary
      sieving electrophoresis (CSE). Over 380 fractions were transferred from the first
      dimensional capillary to the second-dimensional capillary, where components were
      further separated by MEKC and detected by laser-induced fluorescence. Twenty-five
      spots common to the four electropherograms were fit with a 2-D Gaussian surface
      to determine spot position, width, and amplitude. The RSD in CSE mobility was 1.0
      +/- 0.6%. The mean uncertainty in spot position was 1.3 times larger than the
      mean spot width in the CSE dimension. The average SD in MEKC migration time was
      0.37 +/- 0.13 s, which is smaller than the average spot size in this dimension.
      Spot capacity was 200. The RSD in spot amplitude was 50%, reflecting a large cell
      to-cell variation in component expression.

PMID- 17557368
TI  - Cadmium accumulation and binding characteristics in intact Sertoli/germ cell
      units, and associated effects on stage-specific functions in vitro: insights from
      a shark testis model.
AB  - The increased human use of cadmium (Cd) and its increased occurrence in the
      environment is of concern. The testis is sensitive to Cd because of the steroid
      mediated regulation of spermatogenesis, high levels of DNA synthesis and gene
      transcription, all of which varies in a stage-related manner. Validated
      techniques (acridine orange vital staining to detect apoptosis and dextran
      rhodamine exclusion to assess blood-testis barrier function) were recently
      developed and the shark testis was proposed as an alternative model for assessing
      stage-specific functions in living testicular tissue and to study toxicant
      actions on spermatogenesis. The present paper shows that 109Cd accumulation and
      binding in vitro was stage-dependent (premeiotic, PrM > meiotic, M > postmeiotic,
      PoM), rapid and persisted in spermatocysts (intact germ cell/Sertoli cell units)
      49 h after washout. In competitive binding analyses of all three spermatocyst
      stages, Hg, but not Zn, could replace bound 109Cd, suggesting that Cd binding was
      specific. These findings were associated with a biphasic apoptotic response in
      the PrM spermatocysts, which was maximal at 10 microm CdCl2 and 1 microm CdCl2
      after 2 and 4 days in culture, respectively. Although Cd uptake in PoM cysts was
      more than 2-fold less than uptake in PrM cysts, the percentage dextran-rhodamine
      permeant PoM cysts was approximately 8-fold greater than in controls in the
      presence of both 10 microm CdCl2 and 30 microm CdCl2 after 4 days culture,
      indicating that blood-testis barrier function in PoM spermatocysts was
      compromised. These findings demonstrate that this model has utility for use in
      screening assays of environmental toxicants.

PMID- 17557369
TI  - A direct method for ultrasound prediction of day of delivery: a new, population
      based approach.
AB  - OBJECTIVES: To introduce a direct population-based method for prediction of term
      based on ultrasound measurements of the biparietal diameter and femur length in
      the second trimester of pregnancy. METHODS: Our data consisted of 41 343
      ultrasound scans from a non-selected population, prospectively collected during
      the years 1987-2004. Using measurements of biparietal diameter and femur length,
      we constructed prediction curves for term by computing median remaining time of
      pregnancy from the ultrasound measurement to birth. A local linear quantile
      regression method was used to smooth the median and quantile curves. RESULTS: The
      quality of term prediction was stable over the prediction range for both
      biparietal diameter (25-60 mm) and femur length (11-42 mm). The femur-based
      predictions were nearly as good as those of the biparietal diameter. For the
      biparietal diameter, the median of the prediction residual was -0.09 days; 87.2%
      of the births fell within +/- 14 days of the predicted day of delivery, 3.5%
      births were classified as preterm and 4.3% as post-term. The corresponding
      figures for femur length were - 0.04 days, 86.7%, 3.6% and 4.5%. The covariates
      maternal age, parity, mother's smoking habits, sex of the fetus and examination
      year generally affected the predicted term by less than 1 day. CONCLUSIONS: This
      direct ultrasound-based prediction of term using population-based data avoids
      selection biases possibly present in smaller prospective samples. The model
      obviates the dependence on last menstrual period found in standard methods for
      term prediction, and allows an immediate assessment of prediction quality in a
      population setting. The femur-based predictions had a quality similar to those
      based on the biparietal diameter. The model can be updated continuously as new
      data are collected.

PMID- 17557370
TI  - C-terminal incorporation of bio-orthogonal azide groups into a protein and
      preparation of protein-oligodeoxynucleotide conjugates by Cu'-catalyzed
      cycloaddition.

PMID- 17557371
TI  - Circularly polarized luminescence of a fluorescent chiral binaphtylene
      perylenebiscarboxydiimide dimer.

PMID- 17557372
TI  - Site-selective immobilization of ligands with control of density on electroactive
      microelectrode arrays.

PMID- 17557373
TI  - Synthetic CpG oligodeoxynucleotides augment BAFF- and APRIL-mediated
      immunoglobulin secretion.
AB  - The B lymphocyte-activating factor belonging to TNF superfamily (BAFF) acts on B
      lymphocytes through BAFF receptor (BAFF-R), the transmembrane activator, calcium
      modulator, and cyclophilin ligand interactor (TACI), and the B cell maturation
      antigen (BCMA). Another cytokine, a proliferation-inducing ligand (APRIL), only
      binds to TACI and BCMA. In this study, we sought to determine the effect of Toll
      like receptor agonists (TLR-A) on the expression of BAFF/APRIL receptors by
      murine splenic B lymphocytes. CpG oligodeoxynucleotides (ODN) and LPS strongly up
      regulated TACI expression, while BAFF-R was only up-regulated by CpG ODN. CpG ODN
      pretreatment up-regulated TACI expression on follicular and marginal zone B
      lymphocytes and increased their responses to BAFF- and APRIL-mediated Ig
      secretion. TACI seemed to be playing a pivotal role in BAFF- or APRIL-induced Ig
      secretion because B lymphocytes from TACI-knockout mouse or the blocking of TACI
      with a neutralizing antibody resulted in total inhibition of IgA and IgG
      secretion in CpG ODN-pretreated and BAFF- or APRIL-stimulated B cells. Thus, CpG
      ODN-induced increase in TACI expression is likely to play an important role in Ig
      secretion following activation of B lymphocytes through TLR9.

PMID- 17557374
TI  - gammadelta-T cells expressing NK receptors predominate over NK cells and
      conventional T cells in the innate IFN-gamma response to Plasmodium falciparum
      malaria.
AB  - Rapid production of interferon-gamma (IFN-gamma) in response to malaria by the
      innate immune system may determine resistance to infection, or inflammatory
      disease. However, conflicting reports exist regarding the identity of IFN-gamma
      producing cells that rapidly respond to Plasmodium falciparum. To clarify this
      area, we undertook detailed phenotyping of IFN-gamma-producing cells across a
      panel of naive human donors following 24-h exposure to live schizont-infected red
      blood cells (iRBC). Here, we show that NK cells comprise only a small proportion
      of IFN-gamma-responding cells and that IFN-gamma production is unaffected by NK
      cell depletion. Instead, gammadelta-T cells represent the predominant source of
      innate IFN-gamma, with the majority of responding gammadelta-T cells expressing
      NK receptors. Malaria-responsive gammadelta-T cells more frequently expressed
      NKG2A compared to non-responding gammadelta-T cells, while non-responding
      gammadelta-T cells more frequently expressed CD158a/KIR2DL1. Unlike long-term
      gammadelta-T cell responses to iRBC, alphabeta-T cell help was not required for
      innate gammadelta-T cell responses. Diversity was observed among donors in total
      IFN-gamma output. This was positively associated with CD94 expression on IFN
      gamma(+) NK-like gammadelta-T cells. Applied to longitudinal cohort studies in
      endemic regions, similar comparative phenotyping should allow assessment of the
      contribution of diverse cell populations and regulatory receptors to risk of
      infection and disease.

PMID- 17557375
TI  - Transcriptional regulation of MICA and MICB: a novel polymorphism in MICB
      promoter alters transcriptional regulation by Sp1.
AB  - MHC class I-related genes A/B (MICA/B) are ligands of the NKG2D receptor
      expressed on T and NK cells. Their expression is highly restricted in normal
      tissues, but is up-regulated in tumoral and infected cells. We show that the
      minimal promoter of both genes contains a CCAAT box, which binds to NF-Y, and a
      GC box, which binds to Sp1, Sp3 and Sp4. We also demonstrate that MICB promoter
      is polymorphic, showing three single nucleotide polymorphisms (C>G at +16, -341, 
      408) and a deletion of two base pairs at -66 (AG>--) that is located close to the
      CCAAT box (-70) and the GC box (-86). Transcriptional activity associated with
      MICB promoter variants carrying this deletion, present in the 45.3% of Spanish
      population, showed a remarkable decrease (18-fold, p <0.01). By functional
      analysis, we show that the deletion plays a critical role in MICB promoter
      activity by diminishing Sp1 transcriptional activation. These important
      variations in MICB expression among normal individuals could imply a significant
      difference in the natural immune response against infections or tumor
      transformation, and might thereby contribute to an increased aberrant immune
      response against self cells, providing the molecular basis for the associations
      of the MICB gene to different autoimmune diseases.

PMID- 17557376
TI  - IL-12 and IL-18 down-regulate B cell migration in an Ly49D-dependent manner.
AB  - In order to complete their maturation and participate in the humoral immune
      response, immature B cells that leave the bone marrow are targeted to specific
      areas in the spleen, where they differentiate into mature cells. Previously, we
      showed that immature B cells actively down-regulate their integrin-mediated
      migration to LN or to sites of inflammation, enabling their targeting to the
      spleen. This inhibition is mediated by IFN-gamma, which is transcribed and
      secreted at low levels by these immature B cells; its expression is subsequently
      down-regulated following B cell maturation. The activating and inhibitory MHC
      class I receptors, Ly49D and Ly49G2, regulate IFN-gamma secretion in B cells,
      preventing their migration to antigen-enriched sites and their premature
      encounter with an antigen, while enabling their entry into the LN when mature. In
      the present study, we elucidate the pathways by which the Ly49 receptors regulate
      IFN-gamma levels. We show that Ly49D stimulation triggers a signaling cascade
      that increases transcription of both IL-12B and IL-18; these, in turn, can
      interact with their specific receptors, which are expressed at elevated levels on
      immature B cells. Ligation of the IL-12B and IL-18 receptors induces the
      secretion of IFN-gamma, thereby regulating their cytoskeleton rearrangement and
      migration.

PMID- 17557377
TI  - Epigenetic silencing of potentially functional KIR2DL5 alleles: Implications for
      the acquisition of KIR repertoires by NK cells.
AB  - NK cells detect altered patterns of HLA expression in infections and tumors using
      a variegated repertoire of killer cell Ig-like receptors (KIR). Each clone
      surveys different HLA molecules by expressing a limited subset of the KIR encoded
      in its genome, which is maintained throughout cell divisions by epigenetic
      mechanisms (methylation of the nonexpressed genes). How KIR repertoires are
      acquired remains, however, unexplained. Human KIR2DL5 is a useful model for
      studying KIR expression because it has alleles with similar coding regions, but
      drastically divergent expression - whilst some are transcribed in a typically
      clonal manner, others, with distinctive promoter polymorphisms, are nonexpressed.
      Here we investigate the relationship between the sequence diversity of KIR2DL5,
      including three novel alleles, and its variable transcription. The promoters of
      the transcribed alleles recruit the transcriptional regulator RUNX3, whilst a
      mutation shared by all silent alleles precludes this binding. However, all
      promoters are functional in vitro, and pharmacological DNA demethylation of NK
      cells rescues the transcription of silent alleles, indicating that only
      epigenetic mechanisms prevent their inclusion in a normal KIR repertoire. Our
      results are consistent with a model in which RUNX factors could function as
      switch elements in the acquisition of KIR repertoires by NK cell precursors.

PMID- 17557378
TI  - Sonographic estimation of fetal weight: comparison of bias, precision and
      consistency using 12 different formulae.
AB  - OBJECTIVES: To determine the major sources of error in ultrasonographic
      assessment of fetal weight and whether they have changed over the last decade.
      METHODS: We performed a prospective observational study in 1991 and again in 2000
      of a mixed-risk pregnancy population, estimating fetal weight within 7 days of
      delivery. In 1991, the Rose and McCallum formula was used for 72 deliveries.
      Inter- and intraobserver agreement was assessed within this group. Bland-Altman
      measures of agreement from log data were calculated as ratios. We repeated the
      study in 2000 in 208 consecutive deliveries, comparing predicted and actual
      weights for 12 published equations using Bland-Altman and percentage error
      methods. We compared bias (mean percentage error), precision (SD percentage
      error), and their consistency across the weight ranges. RESULTS: 95% limits of
      agreement ranged from - 4.4% to + 3.3% for inter- and intraobserver estimates,
      but were - 18.0% to 24.0% for estimated and actual birth weight. There was no
      improvement in accuracy between 1991 and 2000. In 2000 only six of the 12
      published formulae had overall bias within 7% and precision within 15%. There was
      greater bias and poorer precision in nearly all equations if the birth weight was
      < 1,000 g. CONCLUSIONS: Observer error is a relatively minor component of the
      error in estimating fetal weight; error due to the equation is a larger source of
      error. Improvements in ultrasound technology have not improved the accuracy of
      estimating fetal weight. Comparison of methods of estimating fetal weight
      requires statistical methods that can separate out bias, precision and
      consistency. Estimating fetal weight in the very low birth weight infant is
      subject to much greater error than it is in larger babies.

PMID- 17557379
TI  - ["A medicine of human relationship" revisited--Current neurobiological and
      psychosomatic developments].
AB  - In his programmatic paper published 1989 in this journal, Herbert Weiner held the
      view that psychosomatic medicine has become a medicine of human relations. The
      aim of this review is to reflect if current scientific evidence supports his
      view. Evidence from animal studies suggests that early infant-mother separation
      or neglect not only has a lasting influence on attachment behaviour, but also on
      brain development and the ability for stress regulation mediated by environmental
      as well as genetic factors. Neuronal networks processing affective components of
      physical pain play a role in signalling painful emotional experiences due to
      social isolation and separation. A consistent finding across different studies is
      that physicians who adopt a warm, friendly and reassuring manner help activate
      patients endogenous opioid system, foster their compliance and promote better
      therapeutic results. In summary, evidence from neurobiological studies not only
      support Herbert Weiner's theses but also opens new venues for interdisciplinary
      research.

PMID- 17557380
TI  - [Conference about the significance of patient education in diabetes mellitus].

PMID- 17557381
TI  - The hard cell.
AB  - Ethical quandaries aside, stem-cell science is attracting researchers worldwide.
      Ricki Lewis reports.

PMID- 17557382
TI  - Presentation of the 2006 Morris F. Collen Award to Edward H.(Ted) Shortliffe.

PMID- 17557383
TI  - Testing for suxamethonium apnoea.

PMID- 17557384
TI  - Kudos.

PMID- 17557385
TI  - Assessment of endo therapy is questioned.

PMID- 17557386
TI  - Abram Amsel (1922-2006) in memoriam.

PMID- 17557387
TI  - Temporal integration in Pavlovian appetitive conditioning in rats.
AB  - We used an appetitive sensory preconditioning procedure to investigate temporal
      integration in rats in two experiments. In Phase 1, rats were presented with
      simultaneous compound trials on which a 10-sec conditioned stimulus (CS) X was
      embedded within a 60-sec CS A. In Group Early, CS X occurred during the early
      portion of CS A, whereas in Group Late, CS X occurred during the latter portion
      of CS A. In Phase 2, CS X was paired simultaneously with sucrose. On a subsequent
      test with CS A, the rate of magazine entries peaked during the early portions of
      the stimulus in Group Early and during the latter portions of the stimulus in
      Group Late (Experiments 1 and 2). Similar response peaks were not observed on
      tests with a control stimulus that had been presented in compound with a stimulus
      that did not signal reward (Experiment 2).

PMID- 17557388
TI  - Renewal after overexpectation.
AB  - Four magazine approach experiments were performed with rats to explore the
      decrement produced by reinforcing a compound of two previously conditioned
      stimuli. Compound presentation produced the usual over-expectation decrement in
      responding to the individual stimuli. However, testing in an alternative, but
      similarly treated, context allowed renewal of the initial responding to the
      individual stimuli. This renewal is similar to that seen after a decrement
      produced by nonreinforcement. It joins other results in suggesting that the
      decrement produced in extinction and overexpectation may be due to the same
      mechanism.

PMID- 17557389
TI  - Flavor-evaluative conditioning is unaffected by contingency knowledge during
      training with color-flavor compounds.
AB  - In two experiments, participants inspected and drank a series of drinks, half of
      which contained sugarand half unpalatable Tween20 (tween). Each sugar and tween
      drink had a particular flavor and color. Following this training, the flavors of
      the sugar drinks were assigned higher hedonicevaluations than were those of
      thetween drinks, even though the participants did not reliably report which
      flavors had been present in the sugar and tween drinks during training. Moreover,
      the evaluative conditioning of the flavors was unaffected by whether or not the
      colors alone had been pretrained to predict the presence of sugar or tween in the
      drinks. In accord with Baeyens, Eelen, van den Bergh, and Crombez (1990), we
      conclude that flavor-evaluative conditioning is not mediated by contingency
      learning.

PMID- 17557390
TI  - Selective reinstatement of instrumental performance depends on the discriminative
      stimulus properties of the mediating outcome.
AB  - We conducted three experiments to investigate the associative structure
      underlying the reinstatement of instrumental performance after extinction. In
      each experiment, rats were initially rewarded on two responses with different
      outcomes. At test, both responses were extinguished in order to assess the impact
      of a single noncontingent outcome delivery on response selection. Experiment 1
      found evidence of outcome-selective reinstatement (i.e., more responses were
      performed on the lever that was trained with the reinstating outcome than on the
      other lever). Experiment 2 demonstrated that the outcome's capacity to reinstate
      performance was not affected by a reduction in its motivational value. Experiment
      3 found evidence that the reinstating outcome selectively retrieved the response
      it signaled rather than the response it followed during training. Together, these
      findings are consistent with the view that instrumental reinstatement depends on
      the discriminative stimulus properties of the reinstating outcome.

PMID- 17557391
TI  - Rhesus monkeys (Macaca mulatta) select Arabic numerals or visual quantities
      corresponding to a number of sequentially completed maze trials.
AB  - Four number-trained rhesus monkeys were trained to enumerate their sequential
      responses. After completing a series of computerized maze trials, the monkeys
      were given a same/different discrimination involving a numerical stimulus (an
      Arabic numeral or a visual quantity) and the letter D. The goal was to choose the
      numerical stimulus if it matched the number ofjust-completed maze trials, and to
      choose the letter D if it did not. There were large individual differences in
      performance, but one animal performed above 70% when receiving randomly
      intermixed series of 1, 3, 5, and 9 maze trials. This indicates that the monkey
      was keeping track of the approximate number of maze trials completed in each
      series and using that numerical cue to respond during the same/different
      discrimination.

PMID- 17557392
TI  - Disruption of temporal discrimination and the choose-short effect.
AB  - The present experiment examined the effects of several disruptors on temporal
      discrimination. Pigeons responded under a 0-delay symbolic matching-to-sample
      procedure in which responses to one key color were reinforced following the
      presentation of four shorter sample durations, and responses to another key color
      were reinforced following the presentation of four longer sample durations.
      Steady-state performance was disrupted by presession feeding, intertrial-interval
      food, visual distraction, and extinction. All disruptors decreased temporal
      discrimination accuracy. Analyses of the fitted cumulative normal functions
      indicated that decreases in accuracy were produced mainly by decreases in overall
      stimulus control rather than specific effects on timing. In addition, all
      disruptors selectively decreased accuracy on long-sample trials--a choose-short
      effect. This effect is interpreted in terms of decreased attention to the samples
      under disruption. Current theories of the choose-short effect do not appear to
      easily account for these results.

PMID- 17557393
TI  - Rats acquire a low-response-cost daily time-place task with differential amounts
      of food.
AB  - Gallistel (1990) theorized that when animals encounter a biologically significant
      event, they automatically form a tripartite code consisting of the time, place,
      and nature of the event. Recent research examining such time-place learning (TPL)
      has shown that rats are reluctant to perform TPL tasks and appear to do so only
      under high-response-cost situations (Thorpe, Bates, & Wilkie, 2003; Widman,
      Gordon, & Timberlake, 2000). In the present study, we trained rats on a low
      response-cost daily TPL task, in which the amount of food varied with the
      spatiotemporal contingencies. It was found that rats readily learned this task.
      We hypothesize that, rather than automatically encoding a tripartite code when
      faced with a biologically important event, rats instead automatically encode
      bipartite codes consisting of time-event and event-place information.

PMID- 17557394
TI  - The dental patient and cardiac pacemakers.

PMID- 17557395
TI  - [Analysis of interrelations between lipid spectrum and other clinical laboratory
      parameters in type II diabetes and arterial hypertension in women].

PMID- 17557396
TI  - [Health promotion and prevention in medicine--empowering rather than
      prescribing].

PMID- 17557397
TI  - [Japanese results are difficult to extrapolate to Europe].

PMID- 17557398
TI  - [Dutch people and Flemish people: the same and yet so different?].

PMID- 17557399
TI  - [Choosing individual remedies is a must in homeopathy].

PMID- 17557400
TI  - [An old answer to an old question].

PMID- 17557401
TI  - [These were the right questions].

PMID- 17557402
TI  - [Replacing the hormone replacement therapy].

PMID- 17557403
TI  - Infection control studied at Temple.

PMID- 17557404
TI  - [The welfare effects of economic growth in the Netherlands, 1800-2000].

PMID- 17557405
TI  - Dentist warned of hepatitis risk from refugees.

PMID- 17557406
TI  - Stabilizing mandibular recording bases and occlusal rims.

PMID- 17557407
TI  - Fetal Ireland: national bodies and political agency.

PMID- 17557408
TI  - [Parity and feminist renewal: the specific French features of a cultural change].

PMID- 17557409
TI  - On the role of calcium in chemotaxis and oscillations of dictyostelium cells.
AB  - Migration of differentiated cells to a capillary containing cyclic AMP was
      enhanced in the presence of 1 mM CaCl2 and was virtually absent in the presence
      of 1 mM EGTA. Furthermore, the cells contracted and extended pseudopods to a
      capillary filled with the calcium ionophore A 23187. At short distances,
      migration to the tip of the capillary was observed, THe ionophore also induced
      transient decreases of the optical density of suspended cells indicating changes
      of cell shape. These findings support the hypothesis that cyclic AMP-binding to
      cell surface receptors causes a local influx of calcium ions. These in turn lead
      to an increase of the cytosolic calcium concentration and subsequently to an
      activation of cell migration. Perturbing pulses of the ionophore induced
      permanent phase shifts of free-running light scattering oscillations. This result
      indicates that cytosolic calcium is an intrinsic component of the oscillatory
      system.

PMID- 17557410
TI  - On induction of cell differentiation by cyclic AMP pulses in Dictyostelium
      discoideum.
AB  - Repeated pulses of cyclic AMP, applied at intervals of 5 min, efficiently induced
      differentiation in cells of agip 53, a morphogenetic mutant of Dictyostelium
      discoideum, strain Ax-2. In contrast, pulses applied at intervals of 2 min did
      not induce cell differentiation. To analyze this phenomenon the hydrolysis of
      cyclic AMP between the pulses as well as the effect of the pulses on the
      intracellular concentrations of cyclic GMP were investigated. Experiments
      performed in the presence of added cyclic AMP was not the reason of the
      inefficiency of the pulses applied with a 2-min rhythm. Cyclic AMP pulses applied
      at intervals of 2 min induced discrete increases of the cyclic GMP concentration.
      Limited time resolution at the level of cyclic GMP cannot account for the
      inefficiency of the 2-min pulses.

PMID- 17557411
TI  - Calcium regulates cAMP-induced potassium ion efflux in Dictyostelium discoideum.
AB  - The chemoattractant cAMP elicits a transient efflux of K+ in cell suspensions of
      Dictyostelium discoideum. This cellular response displayed half-maximal activity
      at about 1 microM cAMP and saturated at 100 microM cAMP, cAMP-stimulated K+
      efflux, measured with a K+-sensitive electrode, depended on the extracellular
      free Ca2+ concentration ([Ca2+]0) and was maximal in the presence of EGTA.
      Usually more than 90% of the K+ release could be inhibited by the addition of
      Ca2+. Half-maximal reduction occurred at about 2 microM [Ca2+]0. Inhibition was
      also observed in the presence of caffeine or A23187, drugs known to elevate the
      intracellular free Ca2+ concentration ([Ca2+]i). Under conditions where [Ca2+]0
      was maintained at a low level, half-maximal inhibition was 1 mM for caffeine and
      3 microM for A23187. These results indicate that Cai2+ is involved in the
      regulation of K+ efflux. Simultaneous measurements of Ca2+ uptake and K+ efflux
      induced by cAMP as well as free running oscillations of both ions revealed that
      initiation and termination of Ca2+ uptake slightly preceded those of K+ efflux.

PMID- 17557412
TI  - Oscillations of Ca++ concentration during the cell differentiation of
      Dictyostelium discoideum: their relation to oscillations in cyclic AMP and other
      components.
AB  - Periodic cyclic-AMP pulses control the cell aggregation and differentiation of
      Dictyostelium discoideum. Another component required for the aggregation and
      differentiation of these cells appears to be extracellular Ca+ +. Oscillations in
      extracellular Ca+ + concentration were investigated in suspensions of
      differentiating cells. We observed spike-shaped and sinusoidal Ca+ +
      oscillations. In the course of differentiation, spike-shaped Ca+ + oscillations
      preceded sinusoidal oscillations, and no phase change occurred at the transition
      from spike-shaped to sinusoidal Ca+ + oscillations. Spike-shaped and sinusoidal
      Ca+ + oscillations were related to oscillations in (1) the cyclic-AMP and cyclic
      GMP content of cells, (2) the light-scattering properties of cells, and (3) the
      extracellular pH. Spikeshaped Ca+ + oscillations were observed together with
      cyclic-AMP oscillations. The minima of the extracellular Ca+ + concentration
      trailed the maxima of the cyclic-AMP concentration by about 30 s. Sinusoidal Ca+
      + oscillations were not accompanied by measurable cyclic-AMP oscillations. The
      amplitudes of the sinusoidal Ca+ + oscillations were smaller than those of the
      spike-shaped Ca+ + oscillations. A Ca+ + oscillation of small amplitude (instead
      of a spike-shaped oscillation) was observed when one cyclic-AMP spike was
      skipped. Our results provide evidence for the existence of a sinusoidal cyclic
      AMP-independent Ca+ + oscillation of small amplitude, and they also suggest that
      spike-shaped Ca+ + oscillations may be superimposed on such small-amplitude
      oscillations. When D. discoideum cells produce cyclic-AMP spikes, the uptake of
      additional Ca+ + is induced, resulting in Ca+ + oscillations of a large
      amplitude.

PMID- 17557413
TI  - Microvolt T-wave alternans testing to risk stratify patients being considered for
      ICD therapy for primary prevention of sudden death.

PMID- 17557414
TI  - Medical migration to the U.S.: trends and impact.
AB  - The United States is in the midst of a prolonged nursing shortage, one that could
      reach a deficit of 800,000 registered nurses (RNs) by 2020. Increasingly, foreign
      trained nurses are migrating to the U.S., particularly from low-income countries,
      seeking higher wages and a higher standard of living. Increased reliance on
      immigration may adversely affect health care in lower-income countries without
      solving the U.S. shortage. This Issue Brief analyzes trends in medical migration,
      and explores its short- and long-term effects on the health care workforce in the
      U.S. and in developing countries.

PMID- 17557415
TI  - A genomewide single-nucleotide-polymorphism panel for Mexican American admixture
      mapping.
AB  - For admixture mapping studies in Mexican Americans (MAM), we define a genomewide
      single-nucleotide-polymorphism (SNP) panel that can distinguish between
      chromosomal segments of Amerindian (AMI) or European (EUR) ancestry. These
      studies used genotypes for >400,000 SNPs, defined in EUR and both Pima and Mayan
      AMI, to define a set of ancestry-informative markers (AIMs). The use of two AMI
      populations was necessary to remove a subset of SNPs that distinguished genotypes
      of only one AMI subgroup from EUR genotypes. The AIMs set contained 8,144 SNPs
      separated by a minimum of 50 kb with only three intermarker intervals >1 Mb and
      had EUR/AMI FST values >0.30 (mean FST = 0.48) and Mayan/Pima FST values <0.05
      (mean FST < 0.01). Analysis of a subset of these SNP AIMs suggested that this
      panel may also distinguish ancestry between EUR and other disparate AMI groups,
      including Quechuan from South America. We show, using realistic simulation
      parameters that are based on our analyses of MAM genotyping results, that this
      panel of SNP AIMs provides good power for detecting disease-associated
      chromosomal segments for genes with modest ethnicity risk ratios. A reduced set
      of 5,287 SNP AIMs captured almost the same admixture mapping information, but
      smaller SNP sets showed substantial drop-off in admixture mapping information and
      power. The results will enable studies of type 2 diabetes, rheumatoid arthritis,
      and other diseases among which epidemiological studies suggest differences in the
      distribution of ancestry-associated susceptibility.

PMID- 17557421
TI  - Digital analysis and technical specifications.
AB  - Digital acquisition and analysis of sleep data has become more common over the
      past 20 years. Many investigators have developed strategies to record and analyze
      sleep in a quantitative way. Initially, digital recording and analysis were
      restricted by technical limitations. With current technology, the technical
      limitations of computer acquisition, data storage, and analysis are less
      constraining, and the development of recommendations for the specifications and
      scoring of sleep can be more clearly guided by the goal of characterizing
      physiologic phenomena. In order to develop recommendations and specifications
      regarding digital acquisition and analysis, a literature search, evidence review,
      and standardized consensus process focused on 5 questions regarding computer
      assisted sleep recording and analysis. These questions included: (1) the
      reliability of computerized scoring of sleep stages, (2) the analysis of
      elemental events and waveforms, (3) the physiological and/or clinical
      significance of digitally-analyzed signals, (4) the importance of proposed
      changes in standardized scoring that could incorporate digital analysis, and (5)
      the potential advantages and disadvantages of computerized sleep recordings. Of
      154 studies identified by the search, 119 were found to be suitable for evidence
      review. The evidence review suggested that computer scoring and quantitative
      analysis of sleep is still in the formative stage of development. For many
      technical specification decisions, little or no direct evidence was found,
      although basic engineering principles or standard practices provided some
      rationale which was utilized to develop the recommendations formulated during the
      subsequent UCLA/Rand standardized consensus process.

PMID- 17557422
TI  - The visual scoring of sleep in adults.
AB  - The 1968 Rechtschaffen and Kales (R & K) sleep scoring manual was published 15
      years after REM sleep was discovered. Advances in the ensuing 28 years warranted
      a re-look at visual scoring of sleep stages. This paper describes the work of the
      AASM Visual Scoring Task Force, including methodology, a literature review and
      the rationale behind the new rules. Reliability studies of R & K scoring were
      reviewed; reliability was low for stage one and moderate for slow wave sleep.
      Evidence indicated that K complexes and slow waves are expressed maximal
      frontally, spindles centrally and alpha rhythm over the occipital region. Three
      derivations of EEG, two of electro-oculography, and one of chin EMG were
      recommended. Scoring by 30-second epochs was retained. New terminology for sleep
      stages was proposed. Attenuation of alpha rhythm was determined to be the most
      valid electrophysiological marker of sleep onset. Alternative measures were
      proposed for non-alpha generating subjects. K complexes associated with arousals
      were determined to be insufficient alone to define the new stage N2. No evidence
      was found to justify dividing slow wave sleep into two stages. No reasons were
      found to alter the current slow wave amplitude criteria at any age. The phenomena
      of REM sleep were defined. The rules for defining onset and termination of REM
      sleep periods were simplified. Movement time was eliminated and major body
      movements defined. Studies are needed to test the reliability of the new rules.
      Future advances in technology may require modification of these rules with time.

PMID- 17557423
TI  - The scoring of arousal in sleep: reliability, validity, and alternatives.
AB  - The reliability and validity of EEG arousals and other types of arousal are
      reviewed. Brief arousals during sleep had been observed for many years, but the
      evolution of sleep medicine in the 1980s directed new attention to these events.
      Early studies at that time in animals and humans linked brief EEG arousals and
      associated fragmentation of sleep to daytime sleepiness and degraded performance.
      Increasing interest in scoring of EEG arousals led the ASDA to publish a scoring
      manual in 1992. The current review summarizes numerous studies that have examined
      scoring reliability for these EEG arousals. Validity of EEG arousals was explored
      by review of studies that empirically varied arousals and found deficits similar
      to those found after total sleep deprivation depending upon the rate and extent
      of sleep fragmentation. Additional data from patients with clinical sleep
      disorders prior to and after effective treatment has also shown a continuing
      relationship between reduction in pathology-related arousals and improved sleep
      and daytime function. Finally, many suggestions have been made to refine arousal
      scoring to include additional elements (e.g., CAP), change the time frame, or
      focus on other physiological responses such as heart rate or blood pressure
      changes. Evidence to support the reliability and validity of these measures is
      presented. It was concluded that the scoring of EEG arousals has added much to
      our understanding of the sleep process but that significant work on the
      neurophysiology of arousal needs to be done. Additional refinement of arousal
      scoring will provide improved insight into sleep pathology and recovery.

PMID- 17557424
TI  - The scoring of cardiac events during sleep.
AB  - Standardized guidelines for polysomnography (PSG) have not specified methods for
      acquiring or interpreting electrocardiographic (ECG) data. The practice of single
      lead ECG monitoring during PSG may allow identification of simple measures of
      cardiac rhythm but reduces the ability to detect myocardial ischemia and to
      define cardiac intervals. Although simple measures of cardiac rhythm such as
      heart rate and cardiac pauses are inherently reliable, there is limited data
      regarding outcome measures relative to sleep related heart rates and cardiac
      events during sleep. Several observational and cross-sectional studies
      demonstrate that average heart rate drops nearly 50% from infancy through young
      adulthood and that the average heart rate slows during sleep compared with
      wakefulness; the definitions of sinus bradycardia and sinus tachycardia should
      therefore be lower during sleep than wakefulness. Asystoles of up to 2 seconds
      are seen in normal populations during sleep. Although there may be an increased
      risk of certain arrhythmias at night, particularly in sleep disordered breathing,
      there is no evidence that supports different definitions for these arrhythmias
      during sleep compared with wakefulness. When the quality of tracings permits, the
      standard definitions of narrow- and wide-complex tachycardias and atrial
      fibrillation may be employed. In the future, expansion to multiple ECG leads and
      the use of alternative tools may provide better definition of heart rates and
      cardiac events during sleep.

PMID- 17557425
TI  - The scoring of movements in sleep.
AB  - The International Classification of Sleep Disorders (ICSD-2) has separated sleep
      related movement disorders into simple, repetitive movement disorders (such as
      periodic limb movements in sleep [PLMS], sleep bruxism, and rhythmic movement
      disorder) and parasomnias (such as REM sleep behavior disorder and disorders of
      partial arousal, e.g., sleep walking, confusional arousals, night terrors). Many
      of the parasomnias are characterized by complex behaviors in sleep that appear
      purposeful, goal directed and voluntary but are outside the conscious awareness
      of the individual and therefore inappropriate. All of the sleep-related movement
      disorders described here have specific polysomnographic findings. For the
      purposes of developing and/or revising specifications and polysomnographic
      scoring rules, the AASM Scoring Manual Task Force on Movements in Sleep reviewed
      background literature and executed evidence grading of 81 relevant articles
      obtained by a literature search of published articles between 1966 and 2004.
      Subsequent evidence grading identified limited evidence for reliability and/or
      validity for polysomnographic scoring criteria for periodic limb movements in
      sleep, REM sleep behavior disorder, and sleep bruxism. Published scoring criteria
      for rhythmic movement disorder, excessive fragmentary myoclonus, and hypnagogic
      foot tremor/alternating leg muscle activation were empirical and based on
      descriptive studies. The literature review disclosed no published evidence
      defining clinical consequences of excessive fragmentary myoclonus or hypnagogic
      foot tremor/alternating leg muscle activation. Because of limited or absent
      evidence for reliability and/or validity, a standardized RAND/UCLA consensus
      process was employed for recommendation of specific rules for the scoring of
      sleep-associated movements.

PMID- 17557426
TI  - The scoring of respiratory events in sleep: reliability and validity.
AB  - The American Academy of Sleep Medicine Task Force on Respiratory Scoring reviewed
      the evidence that addresses: the validity of specific sensors in detecting
      airflow, tidal volume, oxyhemoglobin saturation, and CO2; the reliability of
      specific scoring approaches for quantifying sleep related breathing disorders
      (SRBD); and the validity of using various definitions of the apnea hypopnea index
      (AHI) as assessed by the strength and consistency of associations with several
      comorbidities (hypertension, cardiovascular disease, sleepiness, impaired quality
      of life, and accidents). The evidence was based on a literature search of
      relevant articles published through December 2004, which resulted in identifying
      and extracting data from 182 articles, which were graded using standardized
      approaches. Diverse physiological sensors have been utilized to quantify airflow
      limitation in patients with suspected SRBD. Although thermistry appears
      appropriate for identifying apneas, the available evidence did not indicate it
      provides valid quantification of airflow reduction. The emerging evidence
      evaluating the accuracy of signal detection against the gold standard
      measurements (e.g., pneumotachography) suggested the superiority of inductance
      plethysmography and nasal pressure transducers for detection of hypopneas, with
      some evidence that recordings from a nasal pressure transducer may better
      approximate flow/volume than uncalibrated inductance plethysmography. However,
      since the nasal pressure transducer has only recently been incorporated into
      large-scale studies, there are as of yet few data that address the predictive
      value of transducer-identified events relative to clinical or physiological
      outcomes. Very few studies directly compared the validity of alternative
      approaches for defining the duration, amplitude change, and use of corroborative
      data from desaturation or arousal for defining hypopneas. Many observational
      studies utilizing various designs and approaches for event detection have shown
      significant associations between measures of SRBD and health outcomes. Data from
      the 2 largest sleep cohort studies, the Sleep Heart Health Study and the
      Wisconsin Sleep Cohort, both used definitions of hypopneas based on "discernible"
      reductions of inductance plethysmography signals with associated desaturation and
      showed that the derived AHIs using these hypopnea definitions correlated with
      various indices of morbidity. However, it is not clear whether alternative
      definitions would provide comparable if not better prediction, or whether optimal
      approaches for event identification would vary for different outcomes. Despite
      these limitations, forming a consensus on optimal approaches for recording and
      measuring respiratory events is an important step toward generating data from
      different clinical or research laboratories that can be compared. However,
      additional research is needed, including direct comparisons of alternative
      measuring approaches for predicting clinical outcomes, with a need to address
      these issues in large samples across the age spectrum and with inclusion of
      promising new technology.

PMID- 17557428
TI  - Where have all the giants gone?

PMID- 17557427
TI  - The visual scoring of sleep and arousal in infants and children.
AB  - Age is probably the single most crucial factor determining how humans sleep. Age
      and level of vigilance significantly influence the electroencephalogram (EEG) and
      the polysomnogram (PSG). The Pediatric Task Force provide an evidence-based
      review of the age-related development of the polysomnographic features of sleep
      in neonates, infants, and children, assessing the reliability and validity of
      these features, and assessing alternative methods of measurement. We used this
      annotated supporting text to develop rules for scoring sleep and arousals in
      infants and children. A pediatric EEG or PSG can only be determined to be normal
      by assessing whether the EEG patterns are appropriate for maturational age. Sleep
      in infants at term can be scored as NREM and REM sleep because all the
      polysomnographic and EEG features of REM sleep are present and quiet sleep, if
      not NREM sleep, is at least "not REM sleep." The dominant posterior rhythm (DPR)
      of relaxed wakefulness increases in frequency with age: (1) 3.5-4.5 Hz in 75% of
      normal infants by 3-4 months post-term; (2) 5-6 Hz in most infants 5-6 months
      post-term; 3) 6 Hz in 70% of normal children by 2 months of age; and 3) 8 Hz
      (range 7.5-9.5 Hz) in 82% of normal children age 3 years, 9 Hz in 65% of 9-year
      olds, and 10 Hz in 65% of 15-year-old controls. Sleep spindles in children occur
      independently at two different frequencies and two different scalp locations:
      11.0-12.75 Hz over the frontal and 13.0-14.75 Hz over the centroparietal
      electrodes; these findings are most prominent in children younger than 13 years.
      Centroparietal spikes are often maximal over the vertex (Cz), less often maximal
      over the left central (C3) or right central (C4) EEG derivation. About 50% of
      sleep spindles within a particular infant's PSG are asynchronous before 6 months
      of age, 30% at 1 year. Based on this, we recommend that: (1) sleep spindles be
      scored as a polysomnographic signature of NREM stage 2 sleep (N2) at whatever age
      they are first seen in a PSG, typically present by 2 to 3 months post-term; (2)
      identify and score sleep spindles from the frontal and centroparietal EEG
      derivations, especially in infants and children younger than 13 years. NREM sleep
      in an infant or child can be scored if the dominant posterior rhythm occupies
      <50% of a 30-second epoch, and one or more of the following EEG patterns appear:
      (1) a diffuse lower voltage mixed frequency activity; (2) hypnagogic
      hypersynchrony; (3) rhythmic anterior theta of drowsiness; (4) diffuse high
      voltage occipital delta slowing; (5) runs or bursts of diffuse, frontal,
      frontocentral, or occipital maximal rhythmic 3-5 Hz slowing; (6) vertex sharp
      waves; and/or (7) post-arousal hypersynchrony. K complexes first appear 5 months
      post-term and are usually present by 6 months post-term, whereas clearly
      recognizable vertex sharp waves are most often seen 16 months post-term. Vertex
      sharp waves are best seen over the central (Cz, C3, C4) and K complexes over the
      frontal (Fz, F3, F4) electrodes. Slow wave activity (SWA) of slow wave sleep
      (SWS) is first seen as early as 2 to 3 months post-term and is usually present 4
      to 4.5 months post-term. SWA of SWS in an infant or child often has a peak-to
      peak amplitude of 100 to 400 microV. Based on consensus voting we recommended
      scoring N1, N2, and N3 corresponding to NREM 1, 2, and SWS whenever it was
      recognizable in an infant's PSG, usually by 4 to 4.5 months post-term (as early
      as 2-3 months post-term). Epochs of NREM sleep which contain no sleep spindles, K
      complexes, or SWA would be scored as N1; those which contain either K complexes
      or sleep spindles and <20% SWS as N2, and those in which >20% of the 30-second
      epoch contain 0.5 to 2 Hz >75 microV (usually 100-400 microV) activity as N3. The
      DPR should be scored in the EEG channel that is best observed, (typically
      occipital), but DPR reactive to eye opening can be seen in central electrodes.
      Because sleep spindles occur independently over the frontal and central regions
      in children, they should be scored whether they occur in the frontal or central
      regions. Because sleep spindles are asynchronous before age 2 years, simultaneous
      recording of left and right frontal and central activity may be warranted in
      children 1-2 years of age. Simultaneous recording of left, right, and midline
      central electrodes may be appropriate because of the asynchronous nature of sleep
      spindles before age 2 years, but reliability testing is needed. Evidence has
      shown that the PSG cannot reliably be used to identify neurological deficits or
      to predict behavior or outcome in infants because of significant diversity of
      results, even in normal infants. Normal sleep EEG patterns and architecture are
      present in the first year of life, even in infants with severe neurological
      compromise. Increasing evidence suggests that sleep and its disorders play
      critical roles in the development of healthy children and healthy adults
      thereafter. Reliability studies comparing head-to-head different scoring
      criteria, recording techniques, and derivations are needed so that future scoring
      recommendations can be based on evidence rather than consensus opinion. We need
      research comparing clinical outcomes with PSG measures to better inform
      clinicians and families exactly what meaning a PSG has in evaluating a child's
      suspected sleep disorder.

PMID- 17557429
TI  - From the eyes of the beholder--trainees' perspective on the ACGME work-hour
      limits.

PMID- 17557430
TI  - Implementation of the 80-hour work-week limitation for residents has improved
      patient care and education.

PMID- 17557431
TI  - Implementation of the 80-hour work-week limitation for residents has not improved
      patient care and education.

PMID- 17557432
TI  - Treatment of severe snoring with a combination of pseudoephedrine sulfate and
      domperidone.
AB  - STUDY OBJECTIVES: Pharmacologic treatment of severe snoring has not been
      considered to be of great value. The objective of this study was to determine
      whether the combination of a nasal decongestant and a prokinetic drug would
      decrease or eliminate severe snoring. METHODS: Thirty healthy individuals whose
      sleeping partners reported that the patients had severe nightly snoring entered
      an open-label trial of 60 mg of pseudoephedrine and 10 mg of domperidone at
      bedtime for 30 days. Each night's snoring was scored on a diary by the sleeping
      partner. At the end of the open-label trial, a subset of subjects whose snoring
      had recurred were randomized to one or both placebo-controlled trials, either 60
      mg of pseudoephedrine sulfate plus 10 mg of domperidone or to 30 mg of
      pseudoephedrine sulfate plus 10 mg of domperidone. In another placebo-controlled
      trial, the drug combination was compared with each component. RESULTS: In the
      open-label trial, 493 of 772 evaluable subject-nights were free of snoring;
      another 232 nights were scored as mild snoring. In the placebo-controlled trials,
      low-dose therapy caused a reduction in snoring, and high-dose therapy even a
      greater reduction in snoring. The drug combination was more effective than either
      agent alone. CONCLUSION: Treatment with a prokinetic agent plus a nasal
      decongestant reduced or eliminated severe snoring in the majority of subjects
      treated.

PMID- 17557433
TI  - Problem snoring.

PMID- 17557434
TI  - Polysomnography in hospitalized patients using a wireless wide area network.
AB  - BACKGROUND: Sleep-disordered breathing and hypoxemia frequently underlie many
      common medical conditions for which patients require hospitalization. Sleep apnea
      is associated with adverse cardiovascular, neurovascular, inflammatory, and
      metabolic consequences, many of which can be reversed with nasal continuous
      positive airway pressure. Although polysomnography is the gold standard for
      outpatient evaluation of sleep apnea, it has not been used for establishing the
      diagnosis or as a means to intervene with evidence-based therapy in the hospital
      setting. SETTING: A 468-bed tertiary-care facility for adults in which an 801.11b
      wireless network supplements a typical hardwired local area network. METHODOLOGY:
      We developed a technique to perform 16-channel polysomnography on any patient in
      any location in the hospital without interfering with routine nursing care.
      Qualified sleep technicians are able to remotely adjust electrophysiologic and
      respiratory parameters, as well as control continuous positive airway pressure
      titration. The study can also be monitored from any location with Internet access
      using a HIPAA-compliant virtual private network. RESULTS: Polysomnography was
      performed on 51 inpatients (age 26 to 89 years; 31 men). Mean (SD) body mass
      index measured 34.1 kg/m(2) (12.4). Cardiac disease (47%) and neurologic disease
      (27%) were the most frequent primary indications for admission. Data acquisition
      was not disrupted due to connectivity problems. The most frequent deficiencies
      were reduced sleep time (range 0.8-6.5 hours; mean [SD] 3.3 hours [1.6]) and
      reduced or absent rapid eye movement sleep. Mean (SD) apnea-hypopnea index
      measured 35.9 events per hour of sleep (SD 26.3) and 19.4 events per hour of
      total recording time (SD 17.5). CONCLUSIONS: Polysomnography measurements
      transmitted across a wireless wide area network increases the capacity of the
      traditional hospital-based sleep laboratory. This technique can facilitate early
      implementation of appropriate therapy and may reverse underlying factors
      associated with the primary cause of hospitalization. Indications and standards
      of practice need to be specifically established for inpatient polysomnography.

PMID- 17557435
TI  - Tiagabine increases slow-wave sleep in a dose-dependent fashion without affecting
      traditional efficacy measures in adults with primary insomnia.
AB  - INTRODUCTION: This study evaluated dose-response effects of tiagabine on sleep in
      adults with primary insomnia. METHODS: Men and women with primary insomnia (DSM
      IV-TR) were randomly assigned to receive tiagabine 4, 6, 8, 10 mg or placebo in a
      randomized, double-blind, parallel-group study. Efficacy was assessed using
      polysomnography and self-report measures. Safety analyses included measures of
      residual sedation and adverse events. RESULTS: A total of 232 patients (31% men;
      mean age 44.3 years) received study drug. No significant differences were
      observed between tiagabine and placebo in wake after sleep onset, latency to
      persistent sleep, or total sleep time. Significantly greater increases from
      baseline in slow-wave sleep (stages 3 and 4) were found with the 3 highest doses
      of tiagabine compared with placebo (p < .01). Stage 1 sleep showed a
      significantly greater decrease from baseline for all doses of tiagabine than for
      placebo (p < .01). Self-report measures of sleep and daytime function did not
      differ from placebo, except for poorer ratings on the 10-mg dose. Similarly,
      psychomotor performance on the 10-mg dose was worsened compared with placebo.
      Tiagabine was generally well tolerated; dizziness and nausea were the most common
      adverse events, particularly at the 2 higher doses. CONCLUSIONS: In adults with
      primary insomnia, tiagabine significantly increased slow-wave sleep in a dose
      dependent manner with a corresponding significant decrease in Stage 1 sleep,
      whereas no significant differences were observed in wake after sleep onset,
      latency to persistent sleep, or total sleep time compared with placebo.

PMID- 17557436
TI  - Sleep complaints and psychiatric symptoms in children evaluated at a pediatric
      mental health clinic.
AB  - STUDY OBJECTIVES: To examine the association of sleep problems with psychiatric
      symptoms in children evaluated at a university-based outpatient child psychiatry
      clinic. METHODS: Parents of 174 children attending psychiatric services completed
      a 47-item Childhood Sleep Questionnaire and the Behavioral Assessment System for
      Children. Psychiatric diagnosis was obtained through retrospective chart review.
      Sleep characteristics were compared among 4 diagnostic subcategories: attention
      deficit/hyperactivity disorder (ADHD) alone (n=29), ADHD with comorbid mood and
      anxiety disorders (ADHD+; n=50), mood and anxiety disorders alone (n=67), and
      other psychiatric disorders (n= 28). Data from sleep habits survey of 174
      community children without reported psychiatric history served as controls.
      RESULTS: Children with psychiatric disorders had a significantly higher
      prevalence of sleep complaints compared with nonpsychiatric controls. Children
      with ADHD had frequent nocturnal awakenings, bad dreams, and bedtime struggles.
      In addition, the presence of leg jerks during sleep was particularly frequent in
      patients with ADHD compared with any other psychiatric disorder. More frequent
      nighttime awakenings were present in children with mood and anxiety disorders.
      Sleep duration and sleep latency strongly correlated with aggression,
      hyperactivity, and depression. Restless sleep scores highly correlated with all
      psychiatric symptoms. CONCLUSIONS: Sleep problems are highly prevalent among
      children with psychiatric disorders. Children with ADHD and comorbid anxiety or
      mood disorders are more likely to report sleep disturbances. Restless sleep, long
      sleep latency, short sleep duration, and frequent nocturnal awakenings correlate
      with the severity of psychiatric symptoms.

PMID- 17557437
TI  - Effect of a targeted obstructive sleep apnea consult to improve access and
      quality at a sleep disorders center.
AB  - STUDY OBJECTIVES: We sought to evaluate whether a targeted obstructive sleep
      apnea (OSA) consult (TOSAC) protocol that reduced sleep-specialist time spent
      with patients suspected of having OSA would improve quality of care compared with
      the previous clinical method for evaluation of patients internally referred for
      suspected OSA. METHODS: Prospective cohort design. TOSAC patients received
      oximetry and criteria screening prior to a split-night polysomnography and a 45
      minute sleep-specialist consult, while control patients received consult,
      testing, and a follow-up visit (90 minutes of sleep-specialist time). RESULTS: We
      enrolled 186 TOSAC and 94 control patients. TOSAC patients completed their
      evaluation in a median of 7.0 days compared with 60.0 days for the controls (p <
      .001). At baseline, the TOSAC group was sleepier (Epworth Sleepiness Scale 13.9+/
      4.5 vs 11.0+/-4.3; p < .001) and had a slightly lower quality of life (Functional
      Outcomes of Sleep Questionnaire 15.0+/-3.0 vs 16.8+/-2.2, p < .001) than
      controls. The apnea-hypopnea index noted at polysomnography was similar in TOSAC
      and control patients (28.6+/-29.5 vs 23.1+/-23.9, p = .156), and the prevalence
      of OSA was similar in both groups (75% vs 72%, p = .616). At 1 month of therapy,
      improvement in the Epworth Sleepiness Scale and overall patient satisfaction were
      similar between groups (all p > .10), while TOSAC patients had a slightly greater
      improvement on the Functional Outcomes of Sleep Questionnaire (p = .010). TOSAC
      patients reported better subjective continuous positive airway pressure
      compliance (median 42.0 vs 32.5 hours/week; p = .037). CONCLUSIONS: A protocol
      driven evaluation pathway for OSA that used screening with oximetry and less
      sleep-specialist time shortened access and produced similar diagnoses,
      improvements in sleepiness and quality of life, and overall satisfaction.

PMID- 17557438
TI  - Impact of adherence with positive airway pressure therapy on hypercapnia in
      obstructive sleep apnea.
AB  - BACKGROUND: Daytime hypercapnia is common in morbidly obese patients with
      obstructive sleep apnea and is associated with serious complications. Our
      objective was to quantify the effect of adherence with positive airway pressure
      on hypercapnia and hypoxia in these patients. METHODS: We performed a
      retrospective cohort study of 75 patients using a multivariable general linear
      model analysis to identify variables that predicted changes in PaCO2 and PaO2
      after therapy. Bootstrap resampling methods were used to calculate confidence
      intervals for the effects of significant predictors and to internally validate
      the predictive models. RESULTS: The variables that predicted the change in PaCO2
      were average daily hours of positive pressure therapy, FEV1 percentage of
      predicted, and baseline PaCO2 (model R(2) = 0.70). The PaCO2 dropped 1.84 mm Hg
      per hour of adherence and plateaued at 7 hours of average daily use. The PaO2
      improved by approximately 3 mm Hg per hour of adherence and plateaued after 4.5
      hours of therapy (model R2 = 0.48). Patients who used therapy for more than 4.5
      hours per day experienced significant improvements in PaCO2 and PaO2 compared
      with less-adherent patients (APaCO2 7.7+/-5 vs 2.4+/-4 mm Hg, p < .001; delta
      PaO2 9.2+/-11 vs 1.8+/-9 mm Hg, p < .001). For adherent patients, the need for
      daytime home oxygen therapy decreased from 30% to 6% (p = .02). CONCLUSION: In
      hypercapnic patients with obstructive sleep apnea, adherence with positive airway
      pressure is an important modifiable predictor of improvements in PaCO2 and PaO2,
      and its benefit plateaus between 5 and 7 hours of daily therapy.

PMID- 17557439
TI  - Do sleep deprivation and time of day interact with mild obstructive sleep apnea
      to worsen performance and neurobehavioral function?
AB  - STUDY OBJECTIVES: Sleep deprivation, time of day (circadian influences), and
      obstructive sleep apnea (OSA) all reduce performance and neurobehavioral
      function. We assessed the interactive effect of sleep deprivation and time of day
      on performance and neurobehavioral function in subjects with and without mild
      OSA. METHODS: This was a cross-over study in which 13 subjects with mild OSA and
      16 subjects without OSA had performance and neurobehavioral testing after a
      normal night's sleep and after a night of supervised sleep deprivation. All
      subjects were studied in the sleep laboratory of a university teaching hospital.
      Subjects were administered questionnaires to collect demographic, physical, and
      medical information; completed actigraphy and sleep diaries to estimate prior
      sleep debt before testing periods; and were tested on the Neurobehavioral
      Assessment Battery, a personal computer-based driving simulator (AusEd), and the
      Oxford Sleep Resistance Test to assess performance and neurobehavioral function.
      RESULTS: Sleep deprivation resulted in poorer driving simulator and
      neurobehavioral performance for most outcome measures. The worst daytime
      performance was often seen at 3:00 PM. Subjects with mild OSA were less aware of
      their sleepiness due to sleep deprivation and, in 1 reaction time task, showed
      greater impairment than did subjects without OSA at certain times of the day
      after sleep deprivation. CONCLUSIONS: The results suggest that subjects with mild
      OSA are not primarily different than subjects without OSA in their response to
      sleep deprivation or time-of-day influences. Consistent with previous literature,
      there were clear effects of sleep deprivation and time of day in all subjects.
      The finding that perception of daytime sleepiness after sleep deprivation was
      blunted in subjects with OSA compared with subjects without OSA, despite similar
      performance decrements, warrants further study.

PMID- 17557440
TI  - Donepezil in the treatment of narcolepsy.
AB  - Chronic excessive sleepiness impairs the daily life of patients suffering from
      narcolepsy. Antidepressants that enhance synaptic levels of noradrenaline and
      serotonin have been reported as having some therapeutic efficacy. For that
      reason, acetylcholinesterase inhibitors, which elevate acetylcholine levels, may
      have a protective function with respect to narcolepsy and cataplexy. The patient
      reported in this article received donepezil, 10 mg, for 3 consecutive months and
      showed an improvement of the Epworth Sleepiness Scale score from 20 up to 14.

PMID- 17557441
TI  - Pediatric sleep medicine: priorities for research, patient care, policy and
      education.
AB  - STUDY OBJECTIVE: To achieve consensus among pediatric sleep medicine
      practitioners on recommendations for the advancement of the field in the areas of
      research, clinical practice, education, and public policy. METHODS: Leading
      pediatric sleep medicine researchers and clinicians, in collaboration with Brown
      Medical School, convened a conference to discuss the state of the field.
      Participants engaged in multiple discussion panels and work groups, ultimately
      creating recommendations to advance basic and clinical research, clinical
      practice, sleep education, and public policy. RESULTS: Participants reached
      agreement on the major challenges facing the field. Key points of consensus were
      the need to conduct long-term epidemiologic studies of sleep patterns and sleep
      disorders in children, standardize polysomnography and other sleep-measurement
      methodologies, examine the links between insufficient and disrupted sleep in the
      pediatric population and physical and mental health outcomes, and develop
      clinical standards of practice. Attendees also agreed on the need to educate more
      medical health practitioners and the public on pediatric sleep. The importance of
      research on sleep in children and adolescents to inform public policy decisions
      was also endorsed. CONCLUSIONS: Pediatric sleep medicine is a related, but
      unique, discipline within the broader field of sleep medicine. Additional
      research, both basic and clinical, on all aspects of children's sleep is
      necessary to elucidate the neurophysiologic basis of normal sleep development; to
      establish a solid foundation for the evaluation, diagnosis, and treatment of
      pediatric sleep disorders; and to formulate evidence-based public policy in sleep
      health.

PMID- 17557442
TI  - Is it mild obstructive sleep apnea?

PMID- 17557443
TI  - A teenager with insomnia and fatigue; habit or hard wiring?

PMID- 17557444
TI  - Obstructive sleep apnea is more common in boys than in girls.

PMID- 17557445
TI  - Problems with latest Xyrem group investigation.

PMID- 17557446
TI  - Periodic limb movements are associated with disturbed sleep. Pro.

PMID- 17557447
TI  - Periodic limb movements are NOT associated with disturbed sleep. Con.

PMID- 17557448
TI  - Adolescent sleep disturbance and school performance: the confounding variable of
      socioeconomics.
AB  - STUDY OBJECTIVES: To assess how selected socioeconomic variables known to affect
      school performance alter the association between reported sleep disturbance and
      poor school performance in a contiguous middle school/high school population.
      METHODS: A school district/college IRB approved questionnaire was distributed in
      science and health classes in middle school and high school. This questionnaire
      included a frequency scaled pediatric sleep disturbance questionnaire for
      completion by students and a permission and demographic questionnaire for
      completion by parents (completed questionnaires n = 238 with 69.3% including
      GPA). RESULTS: Sleep complaints occur at high frequency in this sample (sleep
      onset insomnia 60% > 1 x /wk.; 21.2% every night; sleepiness during the day
      (45.7% > 1 x /wk.; 15.2 % every night), and difficulty concentrating (54.6% > 1 x
      /wk.; 12.9% always). Students with lower grade point averages (GPAs) were more
      likely to have restless/aching legs when trying to fall asleep, difficulty
      concentrating during the day, snoring every night, difficulty waking in the
      morning, sleepiness during the day, and falling asleep in class. Lower reported
      GPAs were significantly associated with lower household incomes. After
      statistically controlling for income, restless legs, sleepiness during the day,
      and difficulty with concentration continued to significantly affect school
      performance. CONCLUSIONS: This study provides additional evidence indicating that
      sleep disturbances occur at high frequencies in adolescents and significantly
      affect daytime performance, as measured by GPA. The socioeconomic variable of
      household income also significantly affects GPA. After statistically controlling
      for age and household income, the number and type of sleep variables noted to
      significantly affect GPA are altered but persistent in demonstrating significant
      effects on school performance.

PMID- 17557450
TI  - The effect of opioids on sleep architecture.
AB  - STUDY OBJECTIVES: The effect of opioid medications on sleep architecture has been
      demonstrated in patients with comorbid pain or opioid addiction. This study
      examined whether commonly used opioid medications have an adverse effect on sleep
      architecture in healthy adults. METHODS: Forty-two healthy subjects were examined
      with polysomnography after a bedtime dose of placebo, sustained-release morphine
      sulfate (15 mg), or methadone (5 mg) on each of 3 different nights in a double
      blind multiple crossover study in a sleep laboratory in the General Clinical
      Research Center at an academic medical center. RESULTS: Both opioid drugs
      significantly reduced deep sleep and increased stage 2 sleep (both p < .01);
      neither had an effect on sleep efficiency, wake after sleep onset, or total sleep
      time. CONCLUSIONS: Single doses of oral opioid medications can significantly
      affect sleep architecture in healthy adults, and observed reductions in slow-wave
      sleep following opioid administration may have important implications for the
      pathogenesis of opioid-use related fatigue.

PMID- 17557449
TI  - Self-reported sleep, sleepiness, and repeated alcohol withdrawals: a randomized,
      double blind, controlled comparison of lorazepam vs gabapentin.
AB  - STUDY OBJECTIVES: Insomnia is a central symptom of alcohol withdrawal and
      increases relapse potential. The primary objective of this study was to compare
      the efficacy of gabapentin to lorazepam in alleviating sleep disturbances and
      daytime sleepiness during an episode of alcohol withdrawal. The secondary
      objective of this study was to determine if drug treatment efficacy differed by
      the patient history of previous treatments for alcohol withdrawal. METHODS:
      Outpatients in treatment for alcohol withdrawal received a 4-day fixed-dose taper
      of gabapentin or lorazepam in a double-blind, randomized, controlled trial with
      an 8-day follow-up. Daily across a 5 day outpatient treatment and Days 7 and 12
      post-treatment, patients self-reported daytime sleepiness using the Epworth
      Sleepiness Scale. Self-reports of depression (Beck Depression Inventory) were
      completed at Days 1, 5, 7 and 12. Staff assessed daily alcohol withdrawal using
      the Clinical Institute Withdrawal Assessment for Alcohol. From these instruments,
      self-reported sleep and sleepiness were extracted and assessed in the context of
      limited (0-1) or multiple (2 or more) previously treated alcohol withdrawal
      episodes. RESULTS: Patients with limited previous withdrawals reported similar
      treatment effects on self-reports of sleep and sleepiness for gabapentin and
      lorazepam. In contrast, patients with multiple previous alcohol withdrawals
      receiving gabapentin reported reduced sleep disturbances and sleepiness in
      comparison to those receiving lorazepam. CONCLUSIONS: During treatment for
      alcohol withdrawal, gabapentin as compared to standard therapy with lorazepam,
      was superior on multiple sleep measures, in patients who had previous
      withdrawals. Lorazepam subjects experienced rebound symptoms. Early drinking was
      related to persisting insomnia with both drugs.

PMID- 17557451
TI  - Cataplexy Emotional Trigger Questionnaire (CETQ)--a brief patient screen to
      identify cataplexy in patients with narcolepsy.
AB  - STUDY OBJECTIVES: This pilot study explored the sensitivity and specificity of a
      brief survey to determine the presence of cataplexy. We hypothesized that the
      brief questionnaire could provide a quick, sensitive, and specific screening tool
      to identify those patients with cataplexy, which would result in more timely
      referrals for further diagnostic testing. DESIGN: The pilot study utilized a
      brief questionnaire that was developed by including 5 questions that were found
      to be strong positive predictors of cataplexy from a previous 51-item cataplexy
      questionnaire. SETTING: Participants with a laboratory-confirmed diagnosis
      completed the questionnaire via mail correspondence or at the time of scheduled
      appointments in the Mayo Clinic Sleep Disorder Center, Rochester, Minn.
      PARTICIPANTS: Seventy-eight patients with narcolepsy and cataplexy and 78
      patients with obstructive sleep apnea completed the questionnaire. INTERVENTIONS:
      NA. MEASUREMENTS AND RESULTS: The sensitivity, specificity, area under the curve,
      positive predictive value, and negative predictive value/were computed for each
      question individually, along with appropriate 95% confidence intervals.
      CONCLUSIONS: The first item of the cataplexy emotional trigger questionnaire
      (CETQ) discriminates patients with cataplexy from controls with excellent
      sensitivity and specificity. The addition of the other 4 questions, in the
      context of question 1, did not improve specificity, area under the curve,
      positive predictive value, or negative predictive value but did provide useful
      confirmatory data. Thus, a single question provides a brief practical tool that
      could improve the recognition of cataplexy in the clinical setting. Depending on
      the circumstance, users may be interested in utilizing 1 or all 5 questions.

PMID- 17557452
TI  - Potential usefulness of noninvasive autonomic monitoring in recognition of
      arousals in normal healthy children.
AB  - INTRODUCTION: Current methods employed for scoring arousals in children may not
      be sensitive enough. Because arousals are associated with increases in
      sympathetic tone, measurement of sympathetic activity using noninvasive
      techniques could provide useful surrogate markers for arousals in children.
      METHODS: Ten healthy children underwent overnight polysomnographic assessment
      with simultaneous pulse transit time (PTT) and peripheral arterial tonometry
      (PAT) measurements. Arousals (electroencephalogram and/or movement) and PTT and
      PAT events were identified independently, with scorers blinded to the other
      signals. RESULTS: A total of 1985 events were identified in 10 records. Of these,
      657 were electroencephalographic arousals, of which 548 (83%) were identified by
      either PTT and/or PAT. The sensitivity and specificity of PTT for recognizing
      arousals were 0.74 and 0.25, respectively, whereas the sensitivity and
      specificity of PAT for recognizing arousals were 0.57 and 0.13, respectively.
      Because movement arousals result in brief periods of artifact on the PTT and PAT
      signals, we reanalyzed the PTT and PAT events to include artifact events.
      Reanalysis increased the sensitivity of PTT for recognizing arousals to 0.96 and
      that of the PAT to 0.92 and increased PTT and PAT specificity to 0.30 and 0.19,
      respectively. CONCLUSION: Both PTT and PAT events are extremely sensitive
      techniques for arousal recognition in children. Furthermore, a substantial
      proportion of autonomic events occur in children without any accompanying
      visually recognizable electroencephalographic changes, suggesting that PTT and
      PAT may provide useful alternatives for arousal recognition during ambulatory
      sleep monitoring in children.

PMID- 17557454
TI  - Status cataplecticus leading to the obstetric complication of prolonged labor.
AB  - A 32-year-old married Chinese woman with cataplectic narcolepsy developed status
      cataplecticus during childbirth. It resulted in prolonged labor and required an
      emergency cesarean section. The patient had a history of severe and prolonged
      cataplectic attacks during sexual excitement but relatively mild attacks in other
      situations. We postulated that her susceptibility to genital stimulation might
      predispose her to cataplectic attacks during childbirth. Awareness of this
      potential obstetric complication, especially in those with a history of prominent
      sex-related cataplexy, together with careful planning and monitoring during the
      labor process may help to minimize the obstetric risk of patients with
      narcolepsy.

PMID- 17557453
TI  - Evaluation of eszopiclone discontinuation after cotherapy with fluoxetine for
      insomnia with coexisting depression.
AB  - BACKGROUND: Insomnia and major depressive disorder (MDD) may coexist. This study
      evaluated hypnotic discontinuation effects following an 8-week placebo-controlled
      study of eszopiclone/fluoxetine cotherapy in patients with insomnia and comorbid
      MDD. METHODS: Patients meeting DSM-IV criteria for MDD and insomnia received
      fluoxetine each morning for 8 weeks and were randomized to concomitant treatment
      with nightly eszopiclone 3 mg (cotherapy) or placebo (monotherapy). Thereafter,
      patients received 2 weeks of continued fluoxetine plus single-blind placebo.
      RESULTS: Incidence rates of central nervous system (CNS) and potentially CNS
      related adverse events (AEs) during the run-out period were similar between
      treatment groups (8.8% with monotherapy vs 9.8% with cotherapy), and there was no
      evidence of benzodiazepine withdrawal AEs. Physician-assessed Clinical Global
      Impression improvements in depressive symptoms were maintained after eszopiclone
      discontinuation. Improvements in 17-item Hamilton-Depression Rating Scale (HAMD
      17) scores with cotherapy versus monotherapy seen at Week 8 (p = .0004) were
      maintained at Week 10 (p < .0001) and significantly higher depression response
      and remission rates were observed after cotherapy at Week 10 (p < .02). Patients
      discontinued from eszopiclone maintained improvements in SL (sleep latency), WASO
      (wake after sleep onset), and TST (total sleep time) during the 2 weeks following
      discontinuation (p < .05). CONCLUSIONS: In this study, eszopiclone
      discontinuation did not result in significant CNS or benzodiazepine withdrawal
      AEs, rebound insomnia, or rebound depression; and improvements in sleep and
      depressive symptoms were maintained.

PMID- 17557455
TI  - Acute insomnia following surgery of the ventralis intermedius nucleus of the
      thalamus for tremor.
AB  - Stereotactic surgery with lesioning or deep brain stimulation directed to the
      ventralis intermedius nucleus of the thalamus is a well-recognized treatment for
      medically intractable tremor. A patient developed the rare complication of severe
      insomnia, easy awakening, and lack of slow-wave sleep after thalamotomy/deep
      brain stimulation implantation. This complication underscores the role of
      thalamic regulation on initiation and maintenance of sleep.

PMID- 17557456
TI  - Multiple skeletal injuries resulting from uncontrolled restless legs syndrome.
AB  - Restless legs syndrome is a common condition that results in difficulties falling
      and staying asleep and perception of poor sleep quality. We report a case of a 73
      year-old woman with uncontrolled restless legs syndrome who spent most of the
      night standing and walking. As a result of her nighttime behaviors, she fell
      several times and sustained, on several separate occasions, fractures of both
      forearms, ribs, and nose. Iron replacement therapy and changing of her dopamine
      agonist medications resulted in almost complete relief of symptoms. Physicians
      should be aware of the potential for injury in patients with uncontrolled RLS.

PMID- 17557457
TI  - Treating the health, quality of life, and functional impairments in insomnia.
AB  - STUDY OBJECTIVES: Impairments in health, function, and quality of life (QOL) are
      a central feature of insomnia, yet insomnia treatment is targeted solely to
      improving problems falling and staying asleep. It is not even known if the
      nonsleep deficits improve with current treatment. We hypothesized that therapy
      that improves sleep also improves these nonsleep difficulties and carried out
      this review to test that hypothesis. METHODS: A literature search identified the
      health, function, and QOL deficits of insomnia patients. A second search
      determined the effect of insomnia treatments on those problems, capturing
      randomized controlled treatment trials in insomnia patients that included
      relevant measures. RESULTS: Insomnia patients report a variety of symptoms,
      including daytime sleepiness, fatigue, cognitive impairment, symptoms of
      depression, anxiety, health decrements, and impairment in social and occupational
      function. However, the reported deficits are generally not paralleled by
      objective evidence of impairment. Nineteen treatment studies reported measures
      related to these deficits. At least one treatment (eszopiclone [5 studies],
      zopiclone [2 studies], progressive muscle relaxation [2], zolpidem [2], multi
      component cognitive-behavioral therapy [1], doxepin [1], valerian/hops [1], and
      stimulus control [1]) led to a significant improvement compared with placebo in
      at least one of these measures in 14/20 studies. CONCLUSIONS: Treatment can
      improve the perceived health, function, and QOL of insomnia patients. This
      potential improvement signals the need to shift the attention of research and
      clinical practice to include aspects other than sleep difficulties and move
      towards defining successful therapy as not only improving sleep but also
      eliminating deficits in health, function, and QOL.

PMID- 17557458
TI  - The future of behavioral sleep medicine.
AB  - Behavioral Sleep Medicine is a relatively new discipline with roots in Behavioral
      Medicine and a specific focus on behavioral aspects of Sleep Medicine. While
      cognitive behavioral therapy for insomnia is most closely identified with
      Behavioral Sleep Medicine, the discipline and its practitioners offer a wider
      array of interventions for pediatric and adult sleep disorders. Despite the
      existence of these evidenced-based behavioral strategies for the major sleep
      disorders, it is the exception, rather than the norm, when behavioral sleep
      medicine is fully integrated into a sleep medicine practice. A brief history of
      Behavioral Sleep Medicine, challenges to achieving greater integration, progress
      made to date, and suggestions for the immediate future are presented.

PMID- 17557459
TI  - Central apnea during stage 3,4 sleep.

PMID- 17557460
TI  - New-onset insomnia in a middle-aged woman.

PMID- 17557461
TI  - Board Review Corner: the case of the sleepy middle-aged woman.

PMID- 17557462
TI  - Excessive daytime sleepiness among practicing physicians.

PMID- 17557463
TI  - Will physicians eventually become shift workers?

PMID- 17557464
TI  - A team approach to dental sleep medicine.

PMID- 17557465
TI  - CPAP should be used for central sleep apnea in congestive heart failure patients.

PMID- 17557466
TI  - CPAP should not be used for central sleep apnea in congestive heart failure
      patients.

PMID- 17557467
TI  - Effects of a brief behavioral treatment for late-life insomnia: preliminary
      findings.
AB  - STUDY OBJECTIVES: Insomnia is a chronic and prevalent sleep disorder in adults
      older than 65 years. Hypnotics raise safety concerns in this group, and standard
      behavioral treatments are time consuming. This preliminary report addresses the
      effects of a brief behavioral treatment for insomnia in older adults who present
      with the typical psychiatric and medical comorbidities of aging. METHODS: Thirty
      five older adults (10 men, 25 women, mean age = 70.2 +/- 6.4 years old) were
      randomly assigned to a brief behavioral treatment for insomnia (BBTI; n=17) or to
      an information-only control (IC; n=18) condition. All subjects completed
      clinician-administered and self-report measures of sleep quality, as well as a
      sleep diary, at baseline. Interventions were delivered in a single individual
      session with a booster session administered 2 weeks later. Postintervention
      assessments were completed after 4 weeks. RESULTS: Significant improvements in
      self-report and sleep diary measures and mild-to-moderate improvement in anxiety
      and depression were observed after treatment in participants randomly assigned to
      BBTI, as compared with participants randomly assigned to IC. At post-treatment
      assessment, 12 BBTI participants (71%) and 7 IC participants (39%) met criteria
      for response. Nine BBTI participants (53%) met criteria for remission, whereas,
      in the IC group, 3 participants (17%) met the criteria. CONCLUSION: BBTI was
      associated with significant improvements in sleep measures and in daytime
      symptoms of anxiety and depression. BBTI appears to be a promising intervention
      for older adults with insomnia.

PMID- 17557468
TI  - Is brief behavioral treatment for insomnia effective?

PMID- 17557469
TI  - An initial report of sleep disturbance in inactive inflammatory bowel disease.
AB  - BACKGROUND: There is an increased prevalence of gastrointestinal symptoms, peptic
      ulcer disease, and colon cancer in night-shiftworkers, whose sleep is commonly
      disrupted. Sleep complaints are an extrapyramidal symptom of irritable bowel
      syndrome (IBS). Sleep disruption may contribute to increased medical morbidity by
      weakening the ability of the immune system to protect against endotoxins-this
      pathway could be of potential importance to the pathogenesis and/or clinical
      course of inflammatory bowel disease (IBD), a chronic immunoinflammatory
      gastrointestinal disorder associated with marked reductions in quality of life.
      This is the first study to comprehensively examine sleep concerns in patients
      with IBD. METHODS: Sixteen patients with biopsy-proven inactive IBD (8 with Crohn
      disease and 8 with ulcerative colitis), 9 patients with IBS, and 7 healthy
      controls completed the Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale,
      Inflammatory Bowel Disease Questionnaire, SF-12, and a single overnight
      polysomnogram. Polysomnography and arousals were scored according to standard
      criteria. Multivariate analyses were used to compare subjective and objective
      sleep parameters between groups and to identify associations between sleep
      complaints and quality of life. RESULTS: Patients with IBD did not seem to
      significantly differ from patients with IBS, who have established sleep
      complaints. On polysomnography, total sleep time differentiated the 3 groups
      well, with the IBS and IBD groups appearing numerically similar. Whereas IBS and
      IBD groups were similar with respect to observed sleep parameters, IBS patients
      did report the most concerns, consistent with earlier research suggesting that
      hyperarousal and perceptual differences may contribute to symptom reporting.
      CONCLUSION: Sleep parameters greatly influenced quality of life in both groups
      and highlight the need to address sleep concerns as part of IBD management.

PMID- 17557470
TI  - Sleep and residual sedation after administration of zaleplon, zolpidem, and
      placebo during experimental middle-of-the-night awakening.
AB  - STUDY OBJECTIVES: To assess the efficacy of zaleplon 10 mg and zolpidem 10 mg
      administered during experimental middle-of-the-night awakenings in patients with
      sleep-maintenance insomnia using objective polysomnographic measures and to
      assess daytime residual sedation 4 to 7 hours after dosing using sleep-latency
      testing. DESIGN: A randomized, double-blind, placebo-controlled, 3-period,
      crossover design was used to study 37 adults with insomnia who received treatment
      during an experimental awakening 4 hours after bedtime. Latency to persistent
      sleep and total sleep time before and after awakening were recorded. The primary
      residual sedation measure was a sleep latency test conducted hourly from 4 to 7
      hours after treatment. Self-report measure of alertness and concentration and
      digit symbol substitution tests were examined concurrently. SETTING: Sleep
      disorders centers. PATIENTS: Thirty-seven adults with sleep-maintenance insomnia.
      INTERVENTIONS: Zaleplon 10 mg, zolpidem 10 mg, or placebo. MEASUREMENTS AND
      RESULTS: Thirty-one patients had efficacy-evaluable data; 37 patients received at
      least 1 dose of study medication and were included in the safety analysis.
      Compared with placebo, latency to persistent sleep after both zaleplon and
      zolpidem was shorter and total sleep time after administration of the drugs was
      longer (overall p < .001, Dunnett p < .001 for all posthoc comparisons).
      Significant differences from placebo were not found with zaleplon in daytime
      sedation measures. At 4, 5, and 7 hours after zolpidem, sleep onset on sleep
      latency testing was shorter than after placebo (overall p < .001 for all, Dunnett
      tests for posthoc comparisons p < .001, p < .001, p < .05, respectively). Self
      report measures of concentration (4, 5, and 6 hours, overall p < .05, Dunnett p <
      .05 for each time point) and alertness (4 hours, overall p < .05, Dunnett p <
      .05), and Digit Symbol Substitution Test scores (4 and 5 hours, overall p < .001,
      Dunnett p < .01 for both time points) after zolpidem were also lower than with
      placebo. CONCLUSIONS: Zaleplon 10 mg and zolpidem 10 mg effectively shorten sleep
      latency and lengthen sleep duration after dosing, when administered during
      experimental nocturnal awakening. Residual sedation was not detected as little as
      4 hours after zaleplon 10 mg, whereas residual sedation was detected with
      zolpidem 10 mg up to 7 hours after treatment. These findings suggest that
      zaleplon may be an appropriate treatment for use when patients awaken during the
      night and have difficulty reinitiating sleep.

PMID- 17557471
TI  - Correlates of depressive symptoms in patients with obstructive sleep apnea.
AB  - BACKGROUND: Depressive symptoms are common in many different medical illnesses,
      including obstructive sleep apnea. Previous studies have shown conflicting
      results on the relationship of depressive disorders and depressive symptoms with
      sex and severity of sleep apnea. METHODS: Ninety-two men and 29 women diagnosed
      with moderate to severe OSA were reviewed for the presence of depressive symptoms
      and degree of sleepiness using the Beck Depression Inventory (BDI) scores and
      Epworth Sleepiness Scale scores at the time of polysomnography. RESULTS: Higher
      levels of depressive symptoms were reported by women (15.4 +/- 10.5) than men
      (8.1 +/- 6.6) (p < .01). At least mild depressive symptoms (BDI > 10) were found
      in 44.6% of all patients, including 62% of women and 39% of men (p < .05). At
      least moderate depression was present in 11.6% of patients (BDI >19), including
      28% of women and 6% of men (p < .01). The BDI was positively related (p < .001)
      to the desaturation nadir. The degree of daytime sleepiness was unrelated to
      depression severity. CONCLUSION: Depressive symptoms are more common and more
      severe in women with OSA than in men, and this is consistent with results of
      previous studies that showed that depression is more common in women in a broad
      range of settings. Surprisingly, in this study, milder oxygen desaturation nadirs
      were associated with worse depression scores, especially in women, suggesting
      that depressive symptoms in female patients with obstructive sleep apnea
      originate from factors other than traditional measures of obstructive sleep apnea
      severity.

PMID- 17557472
TI  - How many polysomnograms must sleep fellows score before becoming proficient at
      scoring sleep?
AB  - OBJECTIVES: In the field of sleep medicine, there is a paucity of evidence-based
      curriculum development strategies in the literature. We chose to determine the
      number of polysomnograms (PSG) necessary to be scored by sleep fellows in order
      to reasonably approximate sleep scoring by a Diplomate of the American Board of
      Sleep Medicine (DABSM). DESIGN: The fifth PSG scored by two sleep fellows during
      the 12 consecutive months of training was chosen for analysis. A DABSM not
      involved in the training of fellows scored sleep on each of the selected PSG with
      replication of montage and filter settings. Epoch by epoch comparison of sleep
      stage scoring is described as the frequency of concordance between fellow and
      DABSM (f correct). MEASUREMENTS AND RESULTS: The mean (SD) f correct for all PSG
      for each fellow was 0.83 (0.06) and 0.83 (0.08) (p = 0.93). Concordance between
      sleep fellow and DABSM approached 0.8 after scoring between 20-30 PSG. This
      milestone was reached after the fourth month of training. F correct was highest
      for stage 2 sleep and REM sleep and most variable for slow wave sleep and stage 1
      sleep. The variability in f correct for these stages was in part related to the
      relative paucity of these sleep stages. CONCLUSIONS: Scoring of sleep becomes
      reasonably proficient after scoring approximately 20-30 PSG and/or four months of
      dedicated sleep disorders training. A standard measure of concordance that
      corrects for epoch sample size may be helpful for use in future similar
      investigations.

PMID- 17557473
TI  - Newly identified obstructive sleep apnea in hospitalized patients: analysis of an
      evaluation and treatment strategy.
AB  - STUDY OBJECTIVES: Obstructive sleep apnea (OSA) case finding in hospitalized
      patients occurs commonly. In some institutions, the wait time to polysomnography
      (PSG) may be long. We investigated the impact of a protocol utilizing
      autoadjusting continuous positive airway pressure (CPAP) for early initiation of
      therapy in hospitalized patients suspected of having OSA. METHODS: A
      retrospective chart review of patients with likely OSA (oxygen desaturation index
      > or =10 desaturations per hour with symptoms of OSA) hospitalized between 1999
      and 2004 was performed. Subjects were split into intervention and control groups.
      The intervention group (n=62) underwent autoadjusting CPAP titration while
      hospitalized and were discharged on fixed CPAP. The control group subjects (n=62)
      had no autoadjusting CPAP titration and were discharged without CPAP (90% on
      nocturnal oxygen). Both groups then had a follow-up PSG. RESULTS: The 2 groups
      were matched for baseline characteristics, admission diagnoses, and oximetry
      parameters. There were no significant differences in time to PSG or apnea
      hypopnea index at PSG. In the intervention group, autoadjusting CPAP improved,
      but did not normalize, oximetry parameters. No significant differences were found
      in length of hospital stay or in number of urgent care visits, emergency
      department visits, or hospital readmissions pending PSG. Compared with PSG
      determined CPAP pressures, autoadjusting CPAP underestimated the pressure in 60%
      of the intervention group, whereas 21% required bilevel positive airway pressure
      for optimal control. CONCLUSIONS: Compared with oxygen support or no therapy, an
      autoadjusting CPAP-titration protocol did not improve short-term outcomes in
      hospitalized patients with symptoms suggestive of OSA. Autoadjusting CPAP may
      underestimate optimal treatment settings.

PMID- 17557474
TI  - Prevalence and correlates of periodic limb movements in older women.
AB  - STUDY OBJECTIVES: Periodic limb movements of sleep (PLMS) are common in the
      elderly. However, no large polysomnographic study has closely examined the
      relationship of PLMS to sleep architecture and arousals from sleep. We
      investigated the prevalence and correlates of PLMS in a community-based sample of
      older women. DESIGN: Observational study, cross-sectional analyses. SETTING: Two
      clinical sites participating in the Study of Osteoporotic Fractures (SOF).
      PARTICIPANTS: 455 older community-dwelling women (mean age 82.9 years) who
      completed in-home polysomnography at SOF visit 8. INTERVENTIONS: N/A.
      MEASUREMENTS AND RESULTS: In-home 12 channel polysomnography was performed with
      measurement of leg movements by bilateral piezo sensors. Measures of PLMS
      included the number of leg movements per hour of sleep (PLMI) and the number of
      leg movements causing EEG-documented arousals per hour of sleep (PLMA). An
      elevated PLMI was common, with 66% showing PLMI > or =5 and 52% showing PLMI > or
      =15. A PLMA > or =5 and > or =15 were observed in 124 (27%) and 26 (6%)
      participants respectively. After adjustment for the potential confounders of
      antidepressant medication use, age, race, body mass index, and apnea-hypopnea
      index, participants with a higher PLMA had a significantly higher arousal index,
      lower sleep efficiency, higher percentages of sleep stages 1 and 2 and lower
      percentages of stages 3-4 and REM (p < .001). An increased PLMI was associated
      with a higher arousal index, but not with other indices of sleep quality. Neither
      PLMI or PMLA was associated with subjective sleepiness or other known
      comorbidities. CONCLUSIONS: Periodic leg movements are very common in older
      community-dwelling women. PLMS which were associated with EEG arousals had a
      strong and consistent association with markers of disturbed sleep. PLMS
      associated with arousals thus appear to be more clinically relevant and should be
      considered when examining health outcomes associated with PLMS.

PMID- 17557475
TI  - Periodic limb movements in sleep: irrelevant epiphenomenon, marker for a
      potential problem, or a disorder?

PMID- 17557476
TI  - Night-time bradyarrhythmia in a patient with mild obstructive sleep apnea
      syndrome is reversed with CPAP treatment.
AB  - Nocturnal cardiac arrhythmia is a common clinical feature of obstructive sleep
      apnea syndrome. Pathologically relevant rhythm disturbances such as
      atrioventricular block or ventricular tachycardia are known to occur mainly in
      patients with a high apnea-hypopnea index and marked oxygen desaturation. We
      report on a patient with mild obstructive sleep apnea syndrome who nevertheless
      showed intermittent second-degree atrioventricular block during stages of rapid
      eye movement sleep-associated hypopneas. Cardiac arrhythmia was reversed with the
      initiation of nasal continuous positive airway pressure treatment. Based on this
      case report and taking into account known facts from the literature, the finding
      of intermittent second-degree atrioventricular block in our patient with mild
      obstructive sleep apnea syndrome supports careful evaluation of electrocardiogram
      recording acquired during polysomnography in all patients with suspected
      obstructive sleep apnea syndrome.

PMID- 17557477
TI  - Obstructive sleep apnea syndrome as a complication after tracheal surgery.
AB  - We describe a case of obstructive sleep apnea syndrome that occurred after
      tracheal surgery. The patient refused a tracheal stent placement and any surgical
      procedure aimed at stabilizing the tracheal walls. She was treated with a
      continuous positive airway pressure.

PMID- 17557478
TI  - A review of neuroimaging in obstructive sleep apnea.
AB  - STUDY OBJECTIVES: The authors reviewed neuroimaging studies of obstructive sleep
      apnea (OSA) to summarize findings, evaluate their contribution to a current
      understanding of the neurophysiology of the disorder, and propose directions for
      future research. METHOD: Manuscripts were identified using the National
      Institutes of Health PubMed literature search system. Search terms included
      obstructive sleep apnea, sleep apnea, imaging, neuroimaging, magnetic resonance
      imaging, MRI, functional magnetic resonance imaging, fMRI, magnetic resonance
      spectroscopy, and MRS. Inclusion criteria required that research articles (1)
      were written in English, (2) examined an adult population, and (3) focused on
      imaging of the brain. RESULTS: Support for structural abnormalities is mixed, but
      converging evidence suggests the hippocampus may be atrophic in patients with
      OSA. Neurochemical evidence is supportive of white-matter impairment in OSA,
      particularly in the frontal lobes. Functional studies utilizing respiratory
      challenges report widespread neural differences in motor, sensory, and autonomic
      brain regions. Functional neuroimaging cognitive challenges have reported either
      a lack of brain activation in dorsolateral prefrontal cortex or increased neural
      response in frontal lobe, cingulate, thalamus, cerebellum, and juncture of
      parietal and temporal lobes, depending on the cognitive task employed.
      CONCLUSIONS: The current literature examining neuroimaging-derived neural
      correlates in patients with OSA has made many important preliminary
      contributions. Future studies would be strengthened by consideration of potential
      moderating participant characteristics, such as sex, age, education, OSA
      severity, and comorbid conditions. Additional investigation employing
      neuroimaging techniques is needed to advance our understanding of the
      neurophysiology of OSA.

PMID- 17557479
TI  - "Emma's nose". Aggressive management of nasal congestion before initiating PAP
      therapy.

PMID- 17557480
TI  - Sleep talking and noisy grinding. Schedule an appointment with an orthodontist.

PMID- 17557481
TI  - Sleep fragmentation, sleep deprivation, or both.

PMID- 17557482
TI  - Is a patient too sleepy to drive?

PMID- 17557483
TI  - The MSLT/MWT should be used for the assessment of workplace safety.

PMID- 17557484
TI  - The MSLT and MWT should not be used for the assessment of workplace safety.

PMID- 17557485
TI  - A national survey of the effect of sleep medicine specialists and American
      Academy of Sleep Medicine Accreditation on management of obstructive sleep apnea.
AB  - STUDY OBJECTIVES: To study the effect of American Academy of Sleep Medicine
      accreditation of sleep centers and sleep-medicine certification of physicians on
      the management of patients with obstructive sleep apnea (OSA). DESIGN: Cross
      sectional study. SETTING: National web-based survey. PATIENTS: Six hundred thirty
      two patients with OSA. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Self
      reported data on details of whether patients with OSA were using positive airway
      pressure (PAP) devices, timeliness of the initiation of PAP therapy, and overall
      satisfaction of care received from physicians and centers. After adjusting for
      covariates, lack of accreditation or certification status of providers was
      independently associated with discontinuation of PAP therapy (odds ratio [OR]
      1.9, 95% confidence interval [CI], 1.1-3.2; p = .03). Patient education leading
      to perception of risk associated with OSA (OR 0.5, 95% CI, 0.2-0.9) and
      medications for nasal congestion (OR 0.3, 95% CI, 0.1-0.8) "protected" against
      discontinuation of PAP therapy, whereas nasal congestion (OR 1.6, 95% Cl, 1.0
      2.4) increased the likelihood for discontinuation of PAP therapy. Certified
      physicians and accredited centers were more likely to educate their patients and
      received greater satisfaction ratings than non-certified physicians and
      nonaccredited centers (p < .05). Time delays in instituting PAP therapy were not
      influenced by accreditation or certification status, but such delays diminished
      patient satisfaction. CONCLUSIONS: In this web-based survey, accreditation or
      certification status of sleep centers and physicians was associated with better
      indexes of clinical management in patients with OSA. Better patient education
      that fostered risk perception may have been partly responsible for such an
      association. Prospective studies designed to collect objective data regarding the
      effect of accreditation or certification status on outcomes in patients with OSA
      are still needed.

PMID- 17557486
TI  - Specialized sleep care benefits patients.

PMID- 17557487
TI  - Cost-effectiveness of split-night polysomnography and home studies in the
      evaluation of obstructive sleep apnea syndrome.
AB  - STUDY OBJECTIVES: Split-night polysomnography (PSG) and unattended home sleep
      studies have come into use as less-expensive tests for obstructive sleep apnea
      syndrome, but their impact on cost-effectiveness of the overall evaluation and
      treatment is unknown. We compared the cost-effectiveness of evaluations that
      employ these 2 procedures with a conventional approach using full-night PSG.
      METHODS: We used a decision-tree model that incorporated typical clinical
      algorithms for each of the 3 strategies to compare their cost-effectiveness from
      a third-party payer perspective over a 5-year period. Probabilities and test
      characteristics were derived from data from the published literature. Cost
      estimates were based on the 2004 Medicare Fee Schedule. Survival rates were taken
      from National Center for Health Statistics data and published studies.
      Effectiveness was measured as quality-adjusted life years. RESULTS: Trade-offs of
      overall costs versus effectiveness were identified. The home-studies strategy was
      less costly and less effective than split-night PSG and full-night PSG, as was
      split-night PSG compared with full-night PSG. Costs to attain additional quality
      adjusted life years were below commonly accepted thresholds. A probabilistic
      analysis suggested that the home-studies approach was most cost-effective at the
      lowest amounts of third-party willingness to pay, whereas split-night PSG or full
      night PSG was most cost-effective at higher amounts. CONCLUSIONS: Home studies
      and split-night PSG are cost-effective alternatives to full-night PSG.
      Willingness-to-pay is an important consideration in choosing the most cost
      effective approach. This study points out the importance of considering the
      complexities within the entire process of obstructive sleep apnea syndrome
      evaluation when comparing costs among different procedures.

PMID- 17557488
TI  - More isn't always better: cost-effectiveness analysis and the case for using a
      split-night protocol.

PMID- 17557489
TI  - Associations between the use of common medications and sleep architecture in
      patients with untreated obstructive sleep apnea.
AB  - STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is often associated with other
      disorders, which are usually treated with medications. Little is known about the
      extent to which medications are used in the OSA population or the effects of
      common prescription medications on the sleep architecture of patients with OSA.
      The aim of this study was to describe the frequency of use of medications by
      patients with untreated OSA and to examine the potential associations between
      specific, frequently used medication types and indexes of sleep architecture
      assessed through laboratory-based polysomnography. DESIGN: This study used a
      retrospective design with analyses of archival clinical data. SETTING: Tertiary
      public sleep disorders center in Brisbane, Australia. PATIENTS OR PARTICIPANTS:
      Consecutive patients with a clinical diagnosis of OSA (N = 1779). INTERVENTIONS:
      None. MEASUREMENTS AND RESULTS: Of the patients with OSA, 77.1% were taking at
      least 1 medication; 12.4% were taking beta-adrenergic receptor-blocking agents
      and 20.8% were taking antidepressant or anxiolytic medications. Analyses of
      covariance demonstrated reliable effects of medication use on sleep architecture,
      after accounting for age, sex, and body mass index variables. Both tricyclic and
      selective serotonin reuptake inhibitor antidepressant or anxiolytic medications
      were associated with a lower percentage of rapid eye movement sleep and lower
      sleep-efficiency values in patients with OSA, compared with those not taking any
      medications. The use of beta-adrenergic receptor-blocking agents and aspirin had
      no consistent associations with the indexes of sleep architecture. CONCLUSIONS:
      Medication use was high within this sample of patients with OSA. Some common
      medications may be associated with differences in objective sleep quality in a
      large proportion of patients with OSA. The potential effects of classes of common
      medication on both the presentation and treatment of OSA need to be further
      assessed.

PMID- 17557490
TI  - Cross-sectional relationship of reported fatigue to obesity, diet, and physical
      activity: results from the third national health and nutrition examination
      survey.
AB  - STUDY OBJECTIVES: Reported daytime fatigue may be influenced by modifiable risk
      factors. We hypothesized that daytime fatigue is associated with less-favorable
      lifestyle factors, including high body mass index, higher intake of dietary fat,
      and limited physical activity. DESIGN: Cross-sectional analysis. SETTING:
      Population-based survey. PARTICIPANTS: Participants aged 20 to 59 years in the
      Third National Health and Nutrition Examination Survey. INTERVENTIONS: None.
      MEASUREMENTS AND RESULTS: We examined relationships between responses to the
      question, "Right now would you say you are feeling energetic, fresh, average,
      tired or exhausted?" and body mass index, waist circumference, leisure time
      physical activity, and macronutrient intake. Analyses included only people who
      reported getting their usual amount of sleep the night before the evaluation and
      controlled for age, sex, and ethnicity; 5.6%, 14.6%, 58.3%, 19.5%, and 2.0%
      reported that they felt "energetic," "fresh," "average," "tire d," and "ex
      hausted" respectively. There was a U-shaped association across the categories of
      fatigue for physical activity, body mass index, and waist circumference, with the
      healthiest lifestyle factors being associated with reporting feeling "fresh."
      Relative to the fresh group, average, tired and exhausted participants were 1.6,
      1.9, and 3.8 times more likely to report insufficient physical activity, all
      statistically different from the fresh group. This pattern was also observed for
      body mass index and waist circumference and persisted after adjustment for
      covariates and exclusion of individuals with depression. CONCLUSIONS: In adults
      aged 20 to 59 years in the United States, self-reported fatigue is associated
      with higher body mass index, higher waist circumference, and a reduced likelihood
      of getting recommended levels of physical activity.

PMID- 17557491
TI  - Clinical reproducibility of the Epworth Sleepiness Scale.
AB  - STUDY OBJECTIVES: The Epworth Sleepiness Scale (ESS) is widely used as a
      subjective measure of sleepiness. To our knowledge, no study has evaluated its
      reproducibility in the clinical setting. METHODS: A retrospective chart review of
      patients referred to the sleep clinic at Mount Sinai Hospital for evaluation of
      sleep-disordered breathing from a local private snoring clinic between January
      2000 and October 2001 was carried out. Patients were snorers and referred because
      of suspicion of sleep apnea. Clinical information including results of the ESS
      scores from the two institutions was analyzed to evaluate reproducibility.
      RESULTS: There were 142 patients evaluated: 76% men with a mean (SD) age of 44
      (11) years, body mass index of 31 (6.1) kg/m(2), and apnea-hypopnea index of 41
      (34) events per hour. The average time interval between ESS administrations was
      71 (92) days. The average ESS score was 11.1 (5.2) at the Snoring Clinic and 11.2
      (5.3) at Mount Sinai Hospital. The Bland-Altman plot of the difference against
      the mean of the ESS score demonstrated a wide scatter of data and variability
      where 2 SDs ranged 7.8 above and below the mean. A difference between the
      sequential ESS scores of 5 or more was seen in 23% of the subjects. CONCLUSION:
      The ESS score is highly variable when administered sequentially to a clinical
      population being evaluated for a potential sleep-related breathing disorder.

PMID- 17557492
TI  - On the potential clinical relevance of the length of arousals from sleep in
      patients with obstructive sleep apnea.
AB  - STUDY OBJECTIVES: To assess, in individuals referred for evaluation of
      obstructive sleep apnea, the potential clinical significance of brief versus
      longer arousals from sleep. METHODS: Full-night polysomnographic tracings from
      100 patients referred for evaluation of obstructive sleep apnea were analyzed to
      delineate the duration of each arousal event. These data were then correlated to
      the patient's subjective perception of sleepiness as estimated by the Epworth
      Sleepiness Scale (ESS). RESULTS: A significant relationship (p < .0001, r(2) =
      .167) was noted between the frequency of the longer arousals (> 15 seconds) and
      the ESS. This relationship was significant, but distinctly weaker (p = .004, r(2)
      = .073), with the shorter arousals (3-15 seconds); moreover, the association with
      the brief arousals failed to remain significant (p = .678) after controlling for
      the effect of the longer arousals. CONCLUSIONS: Individuals with obstructive
      sleep apnea experience frequent respiratory event associated cortical arousals,
      many of which are greater than 15 seconds in duration. These longer arousals,
      which, in this study, constituted 18.4% of all arousals and accounted for 37.5%
      of the total arousal time, correlate more closely with the ESS than does the
      frequency or time attributable to the more numerous brief arousals. This suggests
      that these more-prolonged arousal events may have a greater impact on the
      restorative aspect of sleep, or on the perception thereof.

PMID- 17557493
TI  - Adaptive servo-ventilation in patients with idiopathic Cheyne-Stokes breathing.
AB  - BACKGROUND: Cheyne Stokes Breathing (CSB), a form of central sleep apnea is often
      found in medical illnesses such as heart failure, stroke or renal failure.
      Adaptive servo-ventilation (ASV) has been reported to be an effective treatment
      of CSB in heart failure. However, there are no reports about using ASV for
      idiopathic CSB, which is not associated with heart failure or other serious
      medical problems. CASE SUMMARY: We evaluated three patients with idiopathic CSB
      and examined the feasibility of using ASV to treat them. The patients had a
      periodic breathing pattern resembling Cheyne-Stokes Breathing. During
      polysomnography, the abnormal breathing pattern was present while patients were
      both awake and asleep. The patients were first tested on continuous positive
      airway pressure (CPAP) and/or oxygen; however they did not respond well to either
      of these treatments. They were then assessed on ASV. The mean abnormal breathing
      events index decreased from 35.2 to 3.5 per hour of sleep on ASV. There was a
      significant reduction in the mean number of arousals caused by abnormal breathing
      events: from 18.5 to 1.1 per hour of sleep. After six to twelve months of using
      ASV, the patients had maintained significant improvement in subjective daytime
      alertness and mood. CONCLUSION: A trial of ASV for patients with idiopathic CSB
      is recommended if they do not have improvement in sleep respiration or daytime
      performance on CPAP and/or oxygen.

PMID- 17557494
TI  - Intravenous magnesium sulfate may relieve restless legs syndrome in pregnancy.
AB  - We report a case of restless legs syndrome that improved after intravenous
      magnesium sulfate administration. A 34-year-old gravida 1 para 0 woman, with a 13
      year history of restless legs syndrome, was prescribed bed rest due to pre-term
      labor at 26 weeks. While at rest, the subject experienced severe restless legs
      syndrome. The subject was later admitted to the hospital for pre-term labor.
      Treatment for pre-term labor included intravenous magnesium sulfate. RLS symptoms
      completely resolved during treatment, beginning the first day of administration.
      Studies involving intravenous magnesium treatment for restless legs syndrome have
      not included pregnant women. The authors propose that intravenous magnesium
      sulfate may alleviate restless legs syndrome in some pregnant women.

PMID- 17557495
TI  - Systematic review of motor vehicle crash risk in persons with sleep apnea.
AB  - STUDY OBJECTIVES: To determine whether drivers with sleep apnea are at increased
      risk of motor vehicle crash; whether disease severity, daytime sleepiness, or
      both disease severity and daytime sleepiness affect this risk, and whether
      treatment of sleep apnea reduces crash risk. DESIGN: Systematic review of
      published literature. SETTING: N/A. PATIENTS/PARTICIPANTS: Patients with sleep
      apnea. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Forty pertinent studies were
      identified. For studies investigating whether noncommercial drivers with sleep
      apnea have increased crash rates, the majority (23 of 27 studies and 18 of 19
      studies with control groups) found a statistically significant increased risk,
      with many of the studies finding a 2 to 3 times increased risk. Methodologic
      quality of the studies did not influence this relationship (p = .22). For
      commercial drivers, only 1 of 3 studies found an increased crash rate, with this
      association being weak (odds ratio of 1.3). The evidence was mixed regarding
      whether the risk of crash involvement is proportional to the severity of the
      sleep apnea, with about half of the studies finding a statistically significant
      increased risk with increased severity. Correlation with subjective daytime
      sleepiness and crash risk was also found in only half of the studies reviewed.
      Treatment of sleep apnea consistently improved driver performance (including
      crashes) across all studies. CONCLUSIONS: Noncommercial drivers with sleep apnea
      are at a statistically significant increased risk of involvement in motor vehicle
      crashes. Studies did not consistently find that daytime sleepiness and the
      severity of sleep apnea were correlated with crash risk. Successful treatment of
      sleep apnea improves driver performance. Clinicians should educate their patients
      with sleep apnea about the importance of treatment adherence for driving safety.

PMID- 17557496
TI  - Sleep medicine--time for a change.
AB  - The growing awareness of obstructive sleep apnea and its profound impact on
      patients' quality of life and health has resulted in an unprecedented growth in
      sleep medicine in the last 2 decades. The present paper argues that, based on
      recently accumulated knowledge about the pathophysiology of cardiovascular
      morbidity in sleep apnea, the practice of sleep medicine must be changed in order
      to improve patients' care. The diagnosis of sleep apnea should be performed when
      patients are aged 25 to 30 years, far younger than the approximately 50 years of
      age, which is when most patients usually receive a diagnosis now, and programs of
      regular follow-up visits to assess patients' condition and compliance with
      treatment should be incorporated into the everyday practice of sleep specialists.
      Because of the wide gap between the number of sleep specialists and sleep clinics
      and the prevalence of sleep apnea in the general population, an alliance between
      sleep medicine and family practitioners is necessary to ensure such changes. A
      proposal for such an alliance is presented.

PMID- 17557497
TI  - Loss of slow-wave sleep.

PMID- 17557498
TI  - Nocturnal wandering in a middle aged man.

PMID- 17557499
TI  - Inappropriate pro/con.

PMID- 17557500
TI  - Understanding GABA and its relation to insomnia and therapeutics.

PMID- 17557501
TI  - GABAA receptors: subtypes, regional distribution, and function.
AB  - Modulatory agents of gamma-aminobutyric acid type A (GABAA) receptors have been
      widely used for more than 40 years to treat anxiety, epilepsy, and sleep
      disorders; these drugs are generally safe, well tolerated, and effective.
      Recently, there has been a substantial growth in understanding of the mechanism
      of action of these drugs, which act at different sites on GABAA receptors. A
      variety of GABAA receptor subtypes with distinct functional roles have been
      characterized and an evolving awareness of GABAA receptor modulation holds
      promise for the future development of new, more sophisticated drug interventions
      that can elicit more selective effects by targeting specific subtypes of GABAA
      receptors. Advances in genetic engineering have led to the development of
      transgenic mouse models that have further refined our understanding of the
      pharmacology and physiology for various GABAA receptor subunits.

PMID- 17557502
TI  - Extrasynaptic GABAA receptors are critical targets for sedative-hypnotic drugs.
AB  - The gamma-aminobutyric acid subtype A (GABAA) receptor is widely considered to be
      an important target for most clinically effective sedative-hypnotic compounds,
      including general anesthetics, benzodiazepines, barbiturates, and gaboxadol or
      THIP (4,5,6,7-tetrahydroisoxazolo (5,4-c)pyridin-3-ol). GABAA receptors are
      highly expressed in anatomical regions that are implicated in sleep processes,
      notably the thalamus. Furthermore, concentrations of these drugs that modify
      behavior in vivo also increase GABA-induced inhibitory conductances in vitro.
      This review will summarize the functional, regional distribution, and
      pharmacologic properties of various classes of GABAA receptors. Particular
      emphasis is placed on subpopulations of GABAA receptors that are expressed in
      extrasynaptic regions of neurons, as these receptors are exquisitely sensitive to
      several classes of sedative-hypnotic compounds. Evidence to date suggests that
      extrasynaptic GABAA receptors can be broadly classified into two groups; those
      containing the delta subunit and the non-delta subunit-containing GABAA
      receptors. Finally, the probable contribution of extrasynaptic GABAA receptors in
      the modulation of sleep will be considered.

PMID- 17557503
TI  - Sleep circuitry and the hypnotic mechanism of GABAA drugs.
AB  - Early in the twentieth century, von Economo provided the first evidence linking
      the hypothalamus with sleep-wake behavior. His studies concluded that the
      anterior hypothalamus was associated with sleep, whereas the posterior
      hypothalamus was associated with waking. In the decades following these
      observations, a wealth of research has shown that an elaborate circuitry
      comprising a number of brain regions, cell types, and extracellular messengers
      underlies sleep-wake behavior. In this review, we discuss data generated in the
      past 10 years that highlight the role of the hypothalamus in sleep-wake behavior
      and control. In particular, we will focus on the identification of the
      ventrolateral preoptic nucleus (VLPO) as a sleep center and the hypocretin/orexin
      cells in the perifornical region of the hypothalamus as constituting a waking
      center; these two centers are critical for the maintenance of normal sleep-wake
      architecture, and provide a foundation for our understanding of sleep-wake
      behavior and its underlying physiology. The data from these and other regions
      traditionally associated with the sleep-wake cycle have led to a flip-flop switch
      model of sleep-wake control. The switch is composed of two sets of mutually
      inhibitory groups of neurons: a sleep group and an arousal group, with the latter
      modulated by orexin-containing neurons in the lateral hypothalamus. The sleep
      promoting GABA (gamma-amino-butyric acid) receptor agonists are a diverse class
      of drugs, which include barbiturates, benzodiazepines, chloral hydrate, ethanol,
      and gaseous anesthetics, that have been used to study sleep physiology for many
      years. Recent studies suggest that these drugs may exert their hypnotic effects
      in a regionally specific manner. For example, some GABAA agonists appear to
      promote sleep by inhibiting the histaminergic cells in the tuberomammillary
      nucleus and weakly activating the VLPO via agonist binding to the alpha1 subunit
      of GABAA receptors; whereas, gaboxadol (THIP; 4,5,6,7-tetrahydroisoxazolo[5,4
      c]pyridin-3-ol) binds to the alpha4delta-subunits, potentially promoting sleep by
      activation of the VLPO. The integration of these data into the flip-flop switch
      model can be used to better understand sleep-wake control and augment existing
      therapeutic treatments for sleep disorders.

PMID- 17557504
TI  - [Correlations between pediatric emergency department and legal medicine in the
      field of child abuse: the usefulness of flow-charts].
AB  - According to the World Health Organization, child abuse is one of the major and
      unrecognised problems affecting the well-being and impairing the harmonic
      development of children and adolescents. Official statistics, provided by Police
      and Courts are not useful for quantifying abuse because these numbers refer to
      cases actually brought to trial, a small part of the amount. In Europe and North
      America more effective measures and intervention programs were set up in order to
      get with a reliable description of this crucial social problem; for example, a
      "dedicated" team performing careful screenings on suspicious cases (Suspected
      Child Abuse and Neglect Teams, SCAN). A legal medical expert joins the team
      bringing his specific experience on lesions from the perspective of
      criminological interpretation, thereby giving a substantial contribution for an
      objective evaluation of available evidence. The multidisciplinary approach can
      give the greatest contribution especially in the initial steps of the evaluation
      of the child. Intervention protocols and guidelines are useful tools to achieve
      this goal, as shown by medical literature. We propose to introduce a flow-chart
      for the initial evaluation of cases, derived from that used in the Canadian
      Paediatric Emergency Departments. This is supposed to be experimentally used by
      health care workers in an Emergency Department setting and to be subsequently
      evaluated both as a diagnostic and a statistic instrument.

PMID- 17557505
TI  - [Laparoscopic surgery in Hirschsprung's disease].
AB  - The laparoscopic treatment of benign conditions of the colon represents only one
      of the numerous application fields of the modern laparoscopic techniques in
      pediatric surgery. Until the half of the 1990's, the surgical treatment of choice
      for Hirschsprung's disease has been the procedure ideated by Soave in the early
      1960's. Nowadays, the optimal treatment in the classic forms of aganglionic
      megacolon consists in performing, in neonatal age or in the first months of life,
      a transanal extramucous pull-through. This approach can be integrated by a
      laparoscopic step. From September 2000, at the Department of Pediatric Surgery,
      Bologna University, we have operated 21 cases of congenital aganglionic megacolon
      with this technique.

PMID- 17557506
TI  - Zofenopril in cardiac surgery.
AB  - The role of ACE-inhibitors in cardiac surgery is still controversial. The
      potential role for zofenopril in preventing ischemia/reperfusion injury in
      cardiac surgery is described.

PMID- 17557507
TI  - Interstitial cells of Cajal network in primary obstructive megaureter.
AB  - OBJECTIVES: Recent reports showed an altered density of interstitial cells of
      Cajal (ICCs) and of peripherin immunoreactive nerve fibres in obstructed uretero
      pelvic junction. Our aim was to investigate ICCs immunoexpression and ureteral
      innervation in primary obstructive megaureter (POM). METHODS: 8 specimens of POM
      were obtained during tailoring. Restricted segments of ureters were divided from
      the dilated ones. C-kit and peripherin immunohistochemistry were performed.
      RESULTS: A normal distribution of ICCs was documented in both circular and
      longitudinal muscular layers of dilated segments. Marked muscular hypoplasia and
      a sparse or absent ICCs occurred in longitudinal muscular layer of restricted
      ureteral segments. A normal distribution of peripherin positive fibres was
      present in both dilated and restricted segments. CONCLUSIONS: Our data confirmed
      a defective muscolarization in restricted, aperistaltic POM. The lacking of ICCs
      in the longitudinal muscular layer is, probably, due to the absence of c-kit
      positive muscular embryological precursors. No alteration of peripherin
      immunoreactive nerve fibres network was observed in both dilated and restricted
      ureteral segments.

PMID- 17557508
TI  - Sarcoglycan immunoreactivity is lacking in infantile hypertrophic pyloric
      stenosis. A confocal laser scanning microscopic study.
AB  - OBJECTIVES: The Dystrophin-Glycoprotein Complex (DGC) is a large multisubunit
      complex that plays a crucial role in maintaining the structural integrity and
      physiology of muscle fibers. Dystrophin has been reported to be absent in the
      pyloric muscle of infantile hypertrophic pyloric stenosis (IHPS) patients. The
      present study was designed to investigate the other two patterns of DGC
      (dystroglycan and sarcoglycan complexes) in normal pyloric muscle and their
      possible modifications in IHPS patients. METHODS: Ten pyloric muscle biopsies
      were obtained from babies operated for IHPS and five control pylorus biopsy taken
      at autopsy from cases without gastrointestinal disease. The DGC sub-complexes
      (beta-dystroglican and beta, delta- sarcoglycans) were localized
      immunohistochemically using specific monoclonal antibodies. The results were
      evaluated using a confocal laser scanning microscope. RESULTS: Positive
      immunolocalization of the two DGC sub complexes was demonstrated in the smooth
      muscle cells (SMCs) of the pyloric region of control patients. Similarly, a
      positive immune expression of beta-dystroglican was observed in the pyloric SMCs
      of IHPS patients. On the other hand a negative immunoreaction for sarcoglycans
      was recorded within the full thickness of the pyloric SMCs of these patients.
      CONCLUSIONS: The absence of sarcoglycans within the hypertrophied pyloric muscle
      may be a predisposing factor in the pathogenesis of IHPS since it could alter the
      normal physiology of SMCs through the modifications of structural integrity of
      sarcolemma and signaling between the extracellular and intracellular compartment.

PMID- 17557509
TI  - [Conservative treatment of pediatric spleen trauma. Twenty years of experience].
AB  - OBJECTIVE: The spleen is the most frequently involved organ in abdominal blunt
      traumas. In the last decade the treatment has changed from an exclusive surgical
      approach to a conservative approach. We report our experience in the last twenty
      years. METHODS: Between 1983-2003, 54 patients with blunt abdominal traumas and
      isolated injury have been treated. The age at the time of diagnosis was 3 to 16
      years (mean, 6.5). The diagnosis was made clinically and with imaging techniques
      (radiographic assessment, scintigraphy, US, CT). In all cases, a conservative
      treatment was started with continuous vital parameters monitoring, blood red
      cells count, hemoglobin, hematocrit; volume infusion and when necessary hemo
      transfusion. Clinical follow-up and US monitoring were performed for six months
      after the trauma. RESULTS: In the period 1983-1993 a conservative treatment was
      tried in 23 patients; in 15 cases it was successfully, in 8 cases a laparotomy
      with splenectomy was necessary due to hemodinamic instability. In the second
      decade we observed 31 patients, all had been treated conservatively. The mean
      hospital stay was of 12 days with no deaths. CONCLUSIONS: Conservative treatment
      for splenic injuries in patients with hemodinamic stability is nowadays the
      treatment choice. Constantly monitoring of clinical, laboratory parameters and
      use of modern imaging techniques allows to follow the evolution of the lesion and
      to avoid, in most cases, a surgical treatment.

PMID- 17557510
TI  - [Castleman's disease in childhood: a case report].
AB  - We report a case of Castleman's disease in 3-month old infant with cervical
      swelling, treated with surgical excision. This case is interesting because of the
      rarity of this disease in childhood, of the cervical localization and of the
      complexity of long- term follow-up.

PMID- 17557511
TI  - Intrauterine depressed skull fracture with spontaneous resolution.
AB  - We describe a full term male infant born by cesarean section, who presented a
      deep round depression of the left parietal bone at birth. MRI scan showed no
      signal alteration on cortical and sub-cortical level in correspondence of the
      depressed skull fracture. At four months of age, a skull X-ray was normal. At 18
      months of age growth and neurologic follow-up is normal.

PMID- 17557512
TI  - [Leigh syndrome with facial abnormalities: a neurocristopathy].
AB  - A case of Leigh syndrome with respiratory chain defect and facial abnormalities
      is reported. Because most of the facial skeleton originates from the neural
      crests, which are strictly connected with the Central Nervous System development,
      the authors speculate that the facial abnormalities, observed in Leigh syndrome,
      are dependent on neural crest development disturbances (dysneurulation) and
      related to neurological features and that Leigh syndrome is a neurocristopathy.
      In case of facial abnormalities in infancy Leigh syndrome with respiratory chain
      defect should be investigated.

PMID- 17557513
TI  - Protecting healthcare workers from tuberculosis in the era of extensively drug
      resistant tuberculosis.

PMID- 17557514
TI  - Risk factors related to the development of diabetes in men working in a north
      Indian industry.
AB  - BACKGROUND: Epidemiological and lifestyle changes have been implicated in the
      high burden of diabetes in urban India. However, longitudinal data on the
      determinants for the development of diabetes in this population are not
      available. We investigated the determinants for the development of diabetes in
      workers in an Indian industrial organization. METHODS: Two cross-sectional
      surveys were done, using similar methodology (Survey 1 during 1995-98 [n=2548]
      and Survey 2 during 2002-03 [n=2800]) among all employees (age 20-59 years) of an
      industrial organization. A large majority of these were men (89.5% in Survey 1
      and 92.8% in Survey 2). Men with no diabetes at baseline, who participated in
      both the surveys (n=942), constituted the study population. Development of new
      onset diabetes was defined using history and fasting glucose concentrations > or
      =7 mmol/L. RESULTS: The mean (SD) age of the participants at baseline was 40 (2)
      years. Diabetes developed in 8% of the study population over 6.8 (1.7) years.
      Individuals who developed diabetes had significantly higher age, blood pressure,
      body mass index, waist circumference, fasting and post-prandial glucose, post
      prandial insulin and fasting triglyceride levels at baseline. On multivariate
      regression analysis, only impaired glucose tolerance (OR 3.8, 95% CI: 2.1-6.8)
      and waist circumference (OR 1.09, 95% CI: 1.02-1.16) predicted the development of
      diabetes. Presence of the metabolic syndrome, as defined by the modified National
      Cholesterol Education Program Adult Treatment Panel (NCEP-ATP) III and WHO
      criteria, increased the odds (95% CI) of developing diabetes by 2.2 (1.3-3.6) and
      4.5 (2.7-7.4) times, respectively. CONCLUSION: Impaired glucose tolerance, high
      waist circumference and the metabolic syndrome are powerful predictors for the
      development of diabetes among urban Indian men.

PMID- 17557515
TI  - Antioxidant vitamin levels in sickle cell disorders.
AB  - BACKGROUND: Sickle cell disorder is a haemoglobinopathy prevalent in the
      Vidharbha region of Maharashtra, central India. With recent evidence of oxidative
      stress in sickle haemoglobinopathy, a possible deficiency of antioxidant vitamins
      was suspected. METHODS: We measured plasma vitamin E, vitamin C and beta-carotene
      levels in persons with heterozygous (n=80) and homozygous sickle cell state
      (n=20), and suitable healthy controls for these groups (n=100 and 66,
      respectively) in a community-based study in the villages near our institution.
      RESULTS: Subjects with heterozygous sickle cell trait had lower vitamin E levels
      than their respective controls (p < 0.05). Subjects with homozygous sickle cell
      disease had lower levels of all three vitamins (p < 0.05). Vitamins E and C
      levels showed a significant positive correlation in both forms of sickle cell
      disorder. CONCLUSION: Our findings suggest that there is depletion of the
      antioxidant vitamins, particularly in severe forms of sickle cell disorder. A
      trial of administration of therapeutic doses of vitamin E in this condition is
      warranted.

PMID- 17557516
TI  - Minimally invasive radioguided surgery for parathyroid adenomas (MIRP).
AB  - BACKGROUND: Parathyroid adenoma is the most common cause of primary
      hyperparathyroidism. Conventional surgical management includes bilateral neck
      exploration with removal of the adenoma(s) and biopsy of one of the other glands
      with visualization of all glands. It is associated with a risk of permanent
      hypoparathyroidism. Radioguided excision of parathyroid adenoma is a widely
      accepted technique which provides accurate localization and complete excision of
      the lesion with low morbidity. We report our experience with this technique.
      METHODS: We performed radioguided excision of parathyroid adenomas in 15
      patients. All of them had preoperative localization of the adenoma using a dual
      tracer, dual phase 99mTc-Sestamibi scan. A dose of 8-10 mCi of 99mTc-Sestamibi
      was injected intravenously 2 hours before surgery. Under local anaesthesia,
      surgical excision of the lesion was done after localizing it using a hand-held
      gamma probe. Complete excision was confirmed by frozen. section of the excised
      lesion and an intraoperative quick parathormone assay. RESULTS: The 99mTc
      Sestamibi scan revealed an increased uptake by the adenoma in all patients and
      complete excision was possible in all the patients. Frozen section confirmed the
      diagnosis and the quick parathormone assay (within 15 minutes) revealed a drop in
      parathormone levels to < 50% after excision in all of them. Three patients
      developed hypocalcaemia postoperatively and were treated with intravenous calcium
      supplementation. At a follow up of 2-29 months, all the patients were
      normocalcaemic. The renal functions improved in 2 of 6 patients who had renal
      failure. CONCLUSION: Minimally invasive radioguided excision of parathyroid
      adenomas is a simple, safe and effective technique associated with a low
      morbidity and can be done as a day-care procedure.

PMID- 17557517
TI  - Role of vitamin A supplementation in the treatment of tuberculosis.
AB  - Vitamin A deficiency has been commonly observed in patients with tuberculosis.
      Low serum retinol levels return to normal after antituberculosis treatment even
      when no supplements are provided. The deficiency of vitamin A observed in
      patients with tuberculosis might have contributed to the development of
      tuberculous disease in them. Alternatively, deficiency could be the result of
      loss of appetite, poor intestinal absorption, increased urinary loss of vitamin A
      or acute phase reaction in TB. Vitamin A deficiency lowers immunity while vitamin
      A supplementation reduces morbidity and mortality, particularly from measles and
      diarrhoea. Vitamin A supplementation also decreases the mortality rate in HIV
      infected children and delays the progression of HIV disease in infected subjects.
      A higher incidence of lung cancer and increased mortality have been observed in
      smokers after beta-carotene supplementation. Zinc deficiency is also common in
      tuberculosis, which may impose a secondary vitamin A deficiency. Clinical trials
      have shown conflicting results regarding the effect of supplementation of vitamin
      A, alone or with other micronutrients, on time taken to sputum conversion in
      patients with pulmonary tuberculosis. Supplementation with multiple
      micronutrients (including zinc) rather than vitamin A alone may be more
      beneficial in patients with tuberculosis, but clinical trials on such a
      combination are lacking.

PMID- 17557518
TI  - Is it possible to retrospectively evaluate multivisceral resections for locally
      advanced colorectal cancer in a population?

PMID- 17557519
TI  - Common bile duct stones: endoscopy or surgery?

PMID- 17557520
TI  - Acute shortage of teachers in medical colleges: existing problems and possible
      solutions.

PMID- 17557522
TI  - The world: a different view.

PMID- 17557521
TI  - Devil's alternative: Will you donate a part of your liver to save an ailing
      relative?

PMID- 17557523
TI  - The Marie Antoinette syndrome.

PMID- 17557524
TI  - Dementia, drugs and doing the right thing.

PMID- 17557525
TI  - Diagnostic medical imaging: rewards and regulations.

PMID- 17557526
TI  - Cryptococcal prostatitis and osteomyelitis.

PMID- 17557527
TI  - Attracting generation next to the rural health sector.

PMID- 17557528
TI  - Outbreak of diarrhoea in Daman and detection of group B rotavirus from three
      adult cases.

PMID- 17557529
TI  - Key findings of the needs assessment survey of the Center for Electronic Health
      Best Practices.

PMID- 17557530
TI  - Making the vision of electronic health records a reality.

PMID- 17557531
TI  - Transforming health care in West Virginia.

PMID- 17557532
TI  - What is medical informatics? One discoverer's journey.

PMID- 17557533
TI  - EMR initiatives at the Robert C. Byrd National Technology Transfer Center at
      Wheeling Jesuit University.

PMID- 17557534
TI  - Solo practitioner finds opening her medical practice with EMR/PMS systems a very
      positive decision.

PMID- 17557535
TI  - Struggles payoff in many ways for physicians who tackle EHR implementation.

PMID- 17557536
TI  - Potential pitfalls with electronic medical records.
AB  - Electronic Medical Record (EMR) systems are a rapidly growing form of
      documentation that has the potential to improve quality of care, physician and
      practice efficiency, and accessibility of stored medical information. However,
      these advances may be met with challenges such as: finances, functionality,
      accessibility, as well as skills necessary for utilization and potential for data
      loss. This article reviews each of these areas in detail to provide further
      insight into the challenges encountered by those implementing EMR systems.

PMID- 17557537
TI  - Financing health information technology.

PMID- 17557538
TI  - Protecting your patients and practice through health information technology.

PMID- 17557539
TI  - Understanding West Virginia's Records Confidentiality Act on the implementation
      of electronic health records.

PMID- 17557540
TI  - Merlin project will transform WVU patient care.

PMID- 17557541
TI  - New Allscripts system to support patient care.

PMID- 17557542
TI  - WVSOM: on the cutting edge of medical education technology.

PMID- 17557543
TI  - [Croatian National Consensus on diagnosis and treatment of obesity].
AB  - Obesity is one of the leading public health problems. Over half of women and two
      thirds of men in Croatia are either overweight or obese, and about one fifth is
      overweight. Especially worrying is the rising prevalence of obesity in children
      and adolescents. Obesity is a chronic disease characterised by metabolic and
      endocrine disorders, resulting in serious chronic complications. The Croatia
      Obesity Society was founded in 2002 under the umbrella of the Croatian Medical
      Association and has so far organised two national congresses on obesity. At each
      congress a national consensus on diagnosing and treating obesity was adopted.
      Taking into account that treating obesity only with recommendations about dieaty
      modification and increased physical activity has not given satisfactory results,
      the 2006 Congress Consesus recommends an earlier start of pharmacologic therapy
      and surgical treatment of obesity compared to 2003 Congress Consensus. We expect
      that the new recommendations will improve diagnostics and treatment of obesity in
      Croatia.

PMID- 17557544
TI  - [Influence of some sociodemographic variables on incidence of negative behaviour
      in nurses' and medical assistants' work environment].
AB  - The aim of this research was to investigate if there are differences in
      experiencing negative behaviour in nurses and medical assistants of different
      sociodemographic status. 1354 nurses and medical assistants participated in this
      research. For the purpose of the research a questionnaire was made, the first
      part of which consisted of questions referring to sociodemographic variables,
      whereas the second part consisted of claims describing negative behaviours. The
      results of the research imply that nurses and medical assistants indicate that
      the most frequent forms of negative behaviour are: disparage, yelling, insulting,
      ignoring one's opinion and attitudes, making some members of the team privileged,
      commenting one's personal life, not securing replacement for absent workers and
      negative attitude towards their work. Nurses more frequently than their
      colleagues experienced the ignoring of their opinion and attitudes. Marital
      status had influence on the experiencing of one aspect (commenting one's personal
      life). The examinees aged 31-50 years, and with the work duration of 11-30 years,
      more frequently experienced yelling, insulting, commenting one's personal life,
      and also making some members of a team in their work environment privileged.

PMID- 17557545
TI  - [Clinical and laboratory characteristics at onset of type 1 diabetes mellitus in
      children].
AB  - The aim was to describe the clinical and laboratory characteristics of diabetes
      mellitus type 1 at its onset. The hospital records at Tuzla pediatric hospital
      were analysed of 109 children aged 0-14 who presented with diabetes between 1990
      and 2005. The data base was divided into three age groups: 0-4.9, 5-9.9 and 10-14
      years - referred to hereafter as the younger, middle and older age groups. We
      found the duration of symptoms prior to diagnosis to be significantly shortest in
      the younger age group. Polyuria, polydipsia and weight loss were the main
      presenting symptoms in all age groups. The median blood glucose value was 26.0
      mmol/L and the pH value was 7.30. The incidence of diabetic ketoacidosis of 48.0%
      and the median HbA 1c value of 10.7% at diagnosis indicate that disease was not
      recognised long before diagnosis. Since our desire is to avoid the development of
      ketoacidosis, it is necessary to educate people who are in permanent contact with
      children about the symptoms of diabetes type 1. This could to a certain degree
      prevent the presentation of the life-threatening condition of diabetic
      ketoacidosis, if the occurrence of diabetes cannot be prevented.

PMID- 17557546
TI  - [Permanent junctional reciprocating tachycardia (PJRT) and dilated
      cardiomyopathy].
AB  - We present 14-year-old girl with permanent junctional reciprocating tachycardia
      which was refractory to medicamentous therapy, who also had dilated
      cardiomyopathy. She underwent successful radiofrequent catheter ablation of
      accessory pathway after wich the histologic changes in the myocardium were
      observed in the form of compensatory hypertrophy of cardiac muscle (cardiac
      remodelling). The question of cause and consequence appeared: whether the
      arrhythmia is a consequence of dilated cardiomyopathy, or it is tachycardia-
      induced cardiomyopathy. This particular issue is discussed in this article. Based
      on the diagnostic procedure and complete recovery of myocardium after catheter
      ablation of accessory pathway, it is obvious that the tachycardia was due to
      tachicardiomyopathy, i.e. cardiomyopathy caused by permanent reciprocating
      junctional tachycardia.

PMID- 17557547
TI  - [Bilateral renal cell carcinoma and concomitant urothelial carcinoma of the renal
      pelvis and ureter: case report].
AB  - We report a patient with ipsilateral synchronous renal cell carcinoma and
      urothelial carcinoma of the left renal pelvis and ureter. The patient underwent
      nephrectomy 9 years earlier due to renal cell cancer of the right kidney. Only 25
      cases of ipsilateral synchronous renal cell carcinoma and urothelial carcinoma
      have been reported in the literature. The median age at diagnosis was 65 years,
      hematuria was the most common presentation and 24% of patients had metastases at
      first examination. Approximately one fourth of the patients had a history of
      cigarette smoking. There is no proof about higher histopathological grade of
      malignancy or specific histological pattern of these tumors when they occur
      synchronously. In the literature there is no report on the synchronous occurrence
      of renal cell carcinoma and urothelial carcinoma of both the renal pelvis and
      ipsilateral ureter.

PMID- 17557548
TI  - [Cyclosporine-induced depressive psychosis in a liver transplant patient: a case
      report].
AB  - Psychotic conditions of iatrogenic nature form a non-negligible portion of
      psychiatric practice. In this paper we present a case of a 62-year-old patient
      with the primary diagnosis of autoimmune hepatitis-induced cirrhosis who
      following the orthotopic liver transplantation developed an episode of depressive
      psychosis. The appearance of symptoms and signs directly correlated with the
      administration of the maximal dose of cyclosporine. The dose was upwardly
      titrated because the laboratory results (an increase in transaminase level) had
      indicated the transplant rejection. Because psychiatric and neurological
      examinations prior to the episode showed no abnormalities, other plausible
      causative factors such as the level of cholesterol and magnesium and the
      concomitant therapy were also analysed. In contrast to the more frequent
      cyclosporine-induced delirium, cyclosporine-induced depressive psychosis has been
      rarely reported in the literature.

PMID- 17557549
TI  - [Spontaneous aortocaval fistula].
AB  - Spontaneous aortocaval fistula is a rare complication of abdominal aortic
      aneurysm rupture. A definitive preoperative diagnosis sometimes is difficult,
      because ofnonspecific and highly variable clinical symptoms. Classic signs such
      as low back pain, palpable pulsatile abdominal mass, abdominal bruit and thrill,
      dyspnea and high-output cardiac failure are present in less than 50% of cases. In
      this article we report the case of a 68-year-old patient with an aortocaval
      fistula who was admitted in hospital because of abdominal pain and hematuria.

PMID- 17557550
TI  - [Treatment of hairy cell leukemia with cladribine].
AB  - Hairy cell leukemia is a chronic B-cell lymphoproliferative disorder
      characterized by clonal proliferation of hairy cells. Treatments of choice are
      purine analogues, particularly cladribine. We treated thirty patients with
      cladribine either by continuous 7-day infusion at a daily dose of 0.1 mg/kg or by
      2-h infusion for 5 consecutive days at a daily dose of 0.14 mg/kg. Remission was
      achieved in 90% of the patients. After a median follow-up of 44 months overall
      survival is 93% and time to treatment failure more than 6 years. Two patients did
      not respond, one patient died of infection shortly after the treatment. Side
      effects resulted mainly from hematological toxicity, 23% of the patients had
      neutropenic fever while 20% required platelets or packed red cell transfusions.
      Our results show that cladribine is safe and effective in the treatment of hairy
      cell leukemia. There were no significant differences in toxicity and response
      between 7-day continuous infusion and 5-day intermittent infusions of the drug.

PMID- 17557551
TI  - [Restless legs syndrome (Wittmaack-Ekbom) "a most common disorder that you never
      heard of"].
AB  - The aim of this article is to provide a survey of scientifically proven knowledge
      about the Restless Legs Syndrome (RLS). The RLS is a neurological condition, a
      disorder of movement with the prevalence amounting from 2 to 15%. Primary RLS
      types are often familial, while the secondary RLS types are sporadic, most often
      caused by iron deficiency, uremia, pregnancy, polyneuropathy, the use of certain
      medications. The diagnosis is based on international diagnostic criteria, while
      the treatment is based on the use of dopaminergic agents, opioids,
      anticonvulsants and benzodiazepines. Doctors specialized in different clinical
      fields encounter patients with RLS, but they rarely diagnose it due to being
      uninformed. The adoption of these knowledges would ensure conducting
      epidemiological studies in the future, which would result in demonstrating real
      data on the spread of this illness within the population of Croatia.

PMID- 17557552
TI  - [Perinatal care in Croatia. Yesterday, today, tomorrow].
AB  - The indicators and determinants of perinatal care in Croatia are presented. The
      maternal mortality is low, less than 10/100.000, at a level of developed
      countries. The perinatal mortality, following stagnation during 10 years at a
      level of around 9.0%o, since 2001 started to decrease for all perinatally dead up
      to the rate of 7.8%, and for those > or =1000 grams or > or =27 weeks up to 5.8%.
      The fetal mortality continues to be stagnant at a rate of about 4.0%, while the
      early neonatal mortality continues to decrease up to the rate of 1.9%. The
      determinants of perinatal care and mortality are analyzed. The pre-term
      deliveries and the births of low birthweight infants (4-6%), of very low
      birthweight infants (0.6%) and of extremely low birthweight infants (0.4%) are at
      the level of developed countries. The antenatal care is continuously improving:
      the average number of antenatal visits increased to 8.1, over 50% of pregnant
      patients had 9 or more visits; the average number of ultrasound examinations
      increased to 3.97, 59% of them had 4 or more US examinations; these values do not
      correspond to the values in very developed countries with very low perinatal
      mortality. The rate of Cesarean sections increased to 15.5%. In neonatal care
      during last 10 years the early mortality of infants > or =2500 grams was
      continuously low , the early mortality of infants 1000-1499 grams and of 1500
      2499 grams is remarkably decreased, but the decrease in those of 500-999 grams
      was not substantial. In neonatal care the lack of equipment and of specialists
      neonatologists, especially in NICU-s is registered. Regional organization of
      perinatal care is voluntary, it is not legally instituted. During 2004, 67.7% of
      all infants and 73.4% of live-born infants with birthweight <1500 grams in the
      3rd level materity wards with NICU were delivered. The causes and regional
      differences in perinatal mortality are analyzed. With the aim to continue in the
      future the positive trend, and to achieve a very low perinatal mortality (<5.0%),
      regional organization of perinatal care, functioning of NICU with adequate
      equipment, and further education of specialists in neonatology and fetal-maternal
      medicine should be institutionally established.

PMID- 17557553
TI  - [Primary bone lymphoma--bone and 67-gallium scintigraphy].

PMID- 17557554
TI  - [Anaemia after kidney transplantation].

PMID- 17557555
TI  - Glucose-6-phosphate dehydrogenase polymorphism and lymphoma risk.
AB  - AIMS AND BACKGROUND: Evidence linking the glucose-6-phosphate dehydrogenase
      (G6PD) polymorphism and risk of non-Hodgkin's lymphoma is conflicting. Risk of
      non-Hodgkin's lymphoma was increased in subjects expressing the G6PD deficient
      phenotype, whereas subjects under medication with statins, a lipid-lowering class
      of drugs partially mimicking G6PD deficiency, seemed to enjoy a protective
      effect. METHODS: We conducted a case-control study on lymphoma risk associated
      with the self-reported G6PD deficient phenotype in 122 lymphoma male cases and
      116 male controls in Sardinia, Italy. The association with the GdMed+ genotype,
      the most frequent variant expressing a deficient enzyme activity, was also tested
      in 49 male lymphoma cases and 31 controls. The WHO classification was used to
      identify lymphoma subentities. RESULTS: Neither self-reported G6PD deficient
      phenotype nor the GdMed+ genotype showed an association with lymphoma risk or its
      subentities. CONCLUSIONS: Our results do not confirm an association either
      positive or negative between the G6PD polymorphism and lymphoma risk.

PMID- 17557556
TI  - Risk of cancer of the prostate and of the kidney parenchyma following bladder
      cancer.
AB  - AIMS AND BACKGROUND: A registry-based cohort study of male patients with bladder
      cancer was conducted to determine the relative risk of second primary cancer of
      the prostate and kidney, the uni-/multivariate differences in relative risk
      according to patient characteristics, the cumulative risk by duration of the
      follow-up, and the prevalence:incidence ratio of prostate and kidney cancer cases
      detected in the first 6 months after the diagnosis of bladder cancer. METHODS:
      The complete case records of all male patients (n = 2025) diagnosed with bladder
      cancer between 1986 and 2002 were extracted from the database of the Romagna
      Cancer Registry: 1539 patients were eligible for analysis of the incidence of
      following prostate and kidney cancers, of the relative risk and the standardized
      incidence ratio specific for the time interval of follow-up. RESULTS: A total of
      108 prostate cancer cases and 23 kidney cancer cases were observed during the
      follow-up. The relative risk of second primary cancer of the prostate and kidney
      was respectively 3.52 (95% CI, 2.89-4.25) and 3.90 (95% CI, 2.47-5.85). The
      absolute excess risk was 11.8 x 1000 for prostate cancer and 2.5 x 1000 for
      kidney cancer. The number of prevalent cases of prostate and kidney cancer
      detected was approximately 10 times greater than the expected number based on
      incidence rates from the general population. During the follow-up, incidence of
      prostate cancer stabilized at a level that was 3- to 4-fold greater than that
      expected. Despite fluctuations, a decrease was also observed for incidence of
      kidney cancer. CONCLUSIONS: In summary, our study showed the relatively constant
      high incidence of prostate and kidney cancers in bladder cancer patients over
      time. The possibility of subsequent cancer implies that an appropriate long
      surveillance is required. The pertinence depends on the duration of the follow-up
      as well as the degree of surveillance.

PMID- 17557557
TI  - Intermittent capecitabine monotherapy with lower dose intensity in heavily
      pretreated patients with metastatic breast cancer.
AB  - AIMS AND BACKGROUND: The purpose of the present retrospective study was to
      evaluate efficacy and safety of a lower dose-intensity capecitabine monotherapy
      regimen in heavily pretreated patients with metastatic breast cancer. METHODS:
      Patients with metastatic breast cancer who had been administered capecitabine
      monotherapy between June 2003 and August 2004 at our hospital were
      retrospectively reviewed. Oral capecitabine (828 mg/m2) was given twice daily for
      three weeks followed by a one-week rest period; this was repeated every four
      weeks. RESULTS: One-hundred and two patients were assessed. Median follow-up of
      patients was 16.4 months. One hundred patients (98%) had been pretreated with
      either anthracyclines or taxanes, 81 patients (79%) with both anthracyclines and
      taxanes. Response rate was 17% (95% CI, 9-24%), and clinical benefit rate was 41%
      (95% CI, 32-51%). Median time-to-treatment failure was 4.9 months, and median
      overall survival time was 24.3 months. This regimen was well tolerated. The most
      frequent grade 3 or 4 adverse event was hand-foot syndrome (6%). Other grade 3 or
      4 adverse events were seen in only 1%-3% of patients. CONCLUSIONS: Intermittent
      capecitabine monotherapy with lower dose intensity achieved a high tumor control
      rate with low toxicity in heavily pretreated metastatic breast cancer patients.

PMID- 17557558
TI  - Induction therapy with paclitaxel and carboplatin followed by hyperfractionated
      radiotherapy plus weekly concurrent chemotherapy and subsequent consolidation
      therapy in unresectable locally advanced non-small-cell lung cancer.
AB  - AIMS AND BACKGROUND: The purpose of this pilot study was to determine the safety
      and feasibility of a complete integrated approach, including induction
      chemotherapy with carboplatin/paclitaxel followed by accelerated
      hyperfractionated radiotherapy with concurrent chemotherapy, and then by
      consolidation chemotherapy for locally advanced stage III non-small cell lung
      carcinoma. METHODS: Systemic doses of carboplatin AUC 6 and paclitaxel (200
      mg/m2), 3 weeks out of 4, were planned as induction and consolidation
      chemotherapy. Weekly carboplatin AUC of 2 plus paclitaxel (50 mg/m2) were given
      during thoracic radiotherapy. RESULTS: Eighteen patients were enrolled: 10 were
      evaluated at the end of chemoradiation and 8 received consolidation chemotherapy.
      On an intent-to-treat basis, 55% of patients achieved a response after induction
      therapy, whereas chemoradiation and consolidation therapy increased the response
      rate by 33% and 16%, respectively. No patient experienced grade > 3 acute
      hematologic toxicity during systemic-dose chemotherapy. With the exception of one
      episode of a severe cardiac adverse event, non-hematologic toxicity was similarly
      tolerable. Severe acute adverse events observed during concurrent chemoradiation
      were mainly represented by esophagitis, resulting in interruption of the
      radiotherapy in 25% of patients. More notably, only one patient experienced
      serious non-hematologic late toxicity. CONCLUSIONS: Although the present approach
      seemed feasible, our data did not support any possible advantage in favor of this
      three-phase integrated treatment, and therefore the design will not be
      investigated in a subsequent phase II study.

PMID- 17557559
TI  - Short hydration regimen and nephrotoxicity of intermediate to high-dose cisplatin
      based chemotherapy for outpatient treatment in lung cancer and mesothelioma.
AB  - AIMS AND BACKGROUND: Cisplatin, a standard component of combination chemotherapy
      for several tumors, presents important anti-tumor properties but also several
      toxic effects. In particular, the major dose-limiting effect appears to be renal
      toxicity. In several countries, to reduce nephrotoxicity after cisplatin
      administration, a 24-h hydration is recommended following a chemotherapy
      treatment in a hospital regimen. In our Institutions, cisplatin chemotherapy is
      an outpatient treatment that provides adequate hydration with an NaCl solution
      plus furosemide and diuresis monitoring during treatment. METHODS AND STUDY
      DESIGN: To assess incidence of cisplatin nephrotoxicity using a short hydration
      regimen, which included 2000 ml of fluids with control of diuresis, individual
      outpatient data was pooled retrospectively from patients enrolled in large
      randomized studies regarding cisplatin-based chemotherapy in lung cancer and
      mesothelioma. From February 1999 to November 2002, 107 patients treated with
      cisplatin (> or = 75 mg/m2/cycle) were examined, monitoring serum creatinine and
      creatinine clearance levels. RESULTS: Five patients out of 107 (4.6%) were
      withdrawn from chemotherapy because of renal toxicity. For the other 102
      patients, serum creatinine and creatinine clearance measurements were stable
      around the normal values during treatment. No time trends relating to serum
      creatinine levels or creatinine clearance and cycle numbers or cisplatin
      cumulative doses were detected (P = 0.36 and P = 0.64, for the relationship with
      cycle number, and P = 0.39 and P = 0.65 for the relationship with cumulative
      dose, respectively, random effect model) after adjusting for the total number of
      cycles administered. CONCLUSIONS: These observations indicate that intermediate
      to high-dose cisplatin administration is feasible in outpatient management with a
      short hydration regimen without high risk of nephrotoxicity.

PMID- 17557561
TI  - Late brain metastases from breast cancer: clinical remarks on 11 patients and
      review of the literature.
AB  - AIMS AND BACKGROUND: Late brain metastases from breast cancer are a rare event.
      Only a few cases have been reported in the English literature. The authors
      describe the clinical and pathological remarks, together with treatment
      modalities, removal extent and overall survival, of 11 patients in whom brain
      metastases were detected more than 10 years from the primary tumor. PATIENTS AND
      METHODS: Between January 1997 and April 2001, we hospitalized 11 patients, all
      females, with a histologically proven diagnosis of brain metastasis from breast
      invasive ductal carcinoma. We defined 'late metastasis' as those metastases that
      appeared at least 10 years after the breast cancer diagnosis. The median age at
      the moment of brain metastasis diagnosis was 59 years (range, 47-70), with a
      median latency time from breast cancer diagnosis of 16 years (range, 11-30).
      RESULTS: Ten patients underwent surgery followed by adjuvant radiotherapy (whole
      brain radiotherapy). Two of them received, after whole brain radiotherapy,
      stereotaxic radio surgery treatment. One patient had stereotaxic brain biopsy,
      performed by neuronavigator, followed by palliative corticosteroid therapy.
      Median survival after brain metastasis diagnosis was 28 months (range, 3 months-4
      years). CONCLUSIONS: Although late brain metastases are a rare event, specific
      neurologic symptoms and neuroradiological evidence of a cerebral neoplasm should
      be correlated to the presence of a cerebral metastasis, in a patient with a
      previous history of breast cancer. The longer latency time from breast cancer to
      brain metastasis could be explained by the "clonal dominance" theory and by
      different genetic alterations of the metastatic cell, which could influence the
      clinical history of the disease.

PMID- 17557560
TI  - A pilot study of a day one and eight every three weeks administration of
      docetaxel in metastatic cancer patients.
AB  - AIMS AND BACKGROUND: Docetaxel is an active agent in metastatic cancers. The
      standard administration every 3 weeks frequently causes gastrointestinal toxicity
      and severe myelosuppression. These are rare with a weekly docetaxel regimen,
      which instead produces severe asthenia. To develop a new docetaxel schedule
      associated with mild myelosuppression and less fatigue, we conducted this pilot
      study to determine the feasibility and the maximum tolerated dose of a day one
      and eight every three weeks administration of docetaxel. PATIENTS AND METHODS:
      The first 3 patients were treated with a dose of 40 mg/m2 on day one and eight,
      which was then escalated by increments of 5 mg/m2 on both days up to determine
      the maximum tolerated dose, defined as the dose level associated with the same
      dose-limiting toxicity in at least 33% of patients. RESULTS: Twenty-one
      metastatic cancer patients entered the study, with a median age of 57 years and a
      median performance status of 1. The escalation of dose continued up to 55 mg/m2,
      where 2 of the 6 enrolled patients presented grade 3 diarrhea, which was our dose
      limiting toxicity. Myelosuppression was mild, and no febrile neutropenia was
      observed. None of the patients showed grade 4 non-haematological toxicity. Only
      9.5% of them presented grade 3 asthenia, whereas grade 3 diarrhea and mucositis
      were revealed in 19% and 9.5%, respectively. All grade 3 non-hematological
      toxicities were observed in heavily pretreated or elderly patients. CONCLUSIONS:
      The recommended dose of docetaxel was 50 mg/m2, but the regimen could not be
      recommended in heavily pretreated patients. However, it could become an option in
      an outpatient setting after a phase II study that better defines its toxicity
      profile and evaluate its antitumor activity.

PMID- 17557562
TI  - Utility of the clinical practice of administering thrombophilic screening and
      antithrombotic prophylaxis with low-molecular-weight heparin to healthy donors
      treated with G-CSF for mobilization of peripheral blood stem cells.
AB  - The aim of the study was to verify the utility of the clinical practice of
      administering thrombophilic screening and antithrombotic prophylaxis with low
      molecular-weight heparin to healthy donors receiving granulocyte colony
      stimulating factor to mobilize peripheral blood stem cells. Thrombophilia
      screening comprised of testing for factor V Leiden G1691A, prothrombin G20210A,
      the thermolabile variant (C677T) of the methylene tetrahydrofolate reductase
      gene, protein C, protein S, factor VIII and homocysteine plasmatic levels,
      antithrombin III activity, and acquired activated protein C resistance. We
      investigated prospectively 72 white Italian healthy donors, 39 men and 33 women,
      with a median age of 42 years (range, 18-65). Five donors (6.9%) were
      heterozygous carriers of Factor V Leiden G1691A; two healthy donors had the
      heterozygous prothrombin G20210A gene mutation; C677T mutation in the methylene
      tetrahydrofolate reductase gene was present in 34 (47.2%) donors in heterozygous
      and in 7 donors (9.7%) in homozygous. Acquired activated protein C resistance was
      revealed in 8 donors of the study (11.1%). The protein C plasmatic level was
      decreased in 3 donors (4.2%); the protein S level was decreased in 7 donors
      (9.7%). An elevated factor VIII dosage was shown in 10 donors (13.9%) and
      hyperhomocysteinemia in 9 donors (12.5%). Concentration of antithrombin III was
      in the normal range for all study group donors. The factor V Leiden mutation was
      combined with the heterozygous prothrombin G20210A in 2 cases and with protein S
      deficiency in one case; 2 healthy donors presented an associated deficiency of
      protein C and protein S. Although none of these healthy subjects had a previous
      history of thrombosis, low-molecular-weight heparin was administered to all
      donors during granulocyte colony-stimulating factor administration to prevent
      thrombotic events. No donor experienced short or long-term thrombotic diseases
      after a median follow-up of 29.2 months. Our data do not support this clinical
      practice because there is no evidence that the combination of granulocyte colony
      stimulating factor to previous hypercoagulable conditions results in thrombotic
      events.

PMID- 17557563
TI  - Sphincter preservation in four consecutive phase II studies of preoperative
      chemoradiation: analysis of 247 T3 rectal cancer patients.
AB  - AIMS AND BACKGROUND: To evaluate the impact of preoperative chemoradiation on
      sphincter preservation in patients with low-medium locally advanced resectable
      rectal cancer treated by four chemoradiation schedules. MATERIALS AND METHODS:
      Between 1990 and 2002, 247 patients were treated according to four schedules of
      chemoradiotherapy: FUMIR (5-fluorouracil, mitomycin, external beam radiotherapy
      37.8 Gy), PLAFUR (cisplatinum, 5-fluorouracil, external beam radiotherapy 50.4
      Gy),TOMRT (raltitrexed, external beam radiotherapy 50.4 Gy), and TOMOXRT
      (raltitrexed, oxaliplatin, external beam radiotherapy 50.4 Gy). Four to five
      weeks after chemoradiation, patients were restaged and surgery was performed 2-3
      weeks later. RESULTS: Overall, the sphincter-saving surgery was performed in
      82.5% of patients. In patients candidate to an abdominoperineal resection before
      chemoradiaton (distance tumor-anorectal ring, < 30 mm) a sphincter-saving surgery
      was possible in 58% of cases: 44% (FUMIR), 52% (PLAFUR), 63% (TOMRT), 76%
      (TOMOXRT) (P < 0.017). The involved surgeons kept the same surgical criteria in
      performing sphincter-saving surgery. After chemoradiation, patients with tumor
      location still between 0 and 30 mm received sphincter-saving surgery according to
      the protocols: 33% (FUMIR), 42% (PLAFUR), 50% (TOMRT), 64% (TOMOXRT) (P = 0.066).
      CONCLUSIONS: Even though the surgeons' skill in performing sphincter-saving
      surgery could be improved with time, the high rate of this procedure in the
      latest schedules suggests an impact of the new drugs in promoting tumor
      downsizing and therefore sphincter-saving surgery.

PMID- 17557564
TI  - In vivo evaluation of melanoma thickness by multispectral imaging and an
      artificial neural network. A retrospective study on 250 cases of cutaneous
      melanoma.
AB  - AIMS AND BACKGROUND: Noninvasive diagnostic methods such as dermoscopy,
      sonography, palpation or combined approaches have been developed in an attempt to
      preoperatively estimate melanoma thickness. However, the clinical presentation is
      often complex and the evaluation subjective. Multispectral image analysis of
      melanomas allows selection of features related to the content and distribution of
      absorbers, mainly melanin and hemoglobin, present within the lesion. Hence, it is
      reasonable to assume that the same features might be useful to predict melanoma
      thickness. METHODS: A multispectral image system was used to analyze in vivo 1939
      pigmented skin lesions. The lesion selection was based on clinical and/or
      dermoscopic features that supported a suspicion for melanoma. All the lesions
      were then subjected to surgery for the histopathological diagnosis, and 250 were
      melanomas. From the multispectral images of the melanomas, we selected 12
      features, seven of which were used to train and test an artificial neural network
      on 155 and 95 melanomas, respectively. RESULTS: Sensitivity (i.e., melanoma > or
      = 0.75 mm thick correctly classified) and specificity (i.e., melanoma < 0.75 mm
      thick correctly classified) evaluated from the receiving operating characteristic
      curves ranged from 76 to 90% and from 91 to 74%, respectively. CONCLUSIONS: Our
      approach provides results similar to those obtained with other methods and has
      the advantage that it is not related to the expertise of the clinician. In
      addition, the physical interpretation of the selected features suggests a
      possible role of spectrophotometry as an objective method to study the natural
      history of the early phases of the disease.

PMID- 17557565
TI  - Significance of suspicious lesions at transrectal ultrasonography in men with
      serum prostate-specific antigen levels of < 20 ng/ml.
AB  - AIMS AND BACKGROUND: The objective of the study was to evaluate the significance
      of suspicious lesions at transrectal ultrasonography for prostate cancer
      diagnosis. PATIENTS AND METHODS: A total of 1,009 men with a mean age of 65.0 +/-
      7.7 years (range, 40.0-79.0) constituted the study cohort and 265 (26.3%) were
      diagnosed with prostate cancer on initial biopsy. RESULTS: The cancer detection
      rate was higher in patients with suspicious lesions (33.2%) than in those with no
      suspicious lesion (21.5%) (P < 0.001). Pathologic findings of the needle biopsy
      samples also showed more aggressive characteristics in men with suspicious
      lesions (P < 0.05). Of 413 men with suspicious lesions, additional lesion
      directed biopsies were performed in 133 patients. The positive predictive value
      of additional lesion-directed biopsy was 18.0%. Of patients who had positive
      cores on lesion-directed biopsies, all were also found to have positive cores on
      random biopsies, and no patient had positive cores only on lesion-directed
      biopsies. The Gleason score was not changed by the findings of lesion-directed
      biopsies in these patients. CONCLUSIONS: Our findings do not provide a rationale
      to recommend the addition of lesion-directed biopsy in patients with suspicious
      lesions at transrectal ultrasonography. However, men with suspicious lesions at
      transrectal ultrasonography had a higher risk of being diagnosed with prostate
      cancer.

PMID- 17557566
TI  - P53 gene mutations in surgical margins and primary tumor tissues of patients with
      squamous cell carcinoma of the head and neck.
AB  - AIMS AND BACKGROUND: The frequency of p53 mutations in primary tumors, the effect
      of the mutations on some clinical and pathological features of head and neck
      squamous cell carcinoma, and the impact of p53 mutations in the surgical margins
      on local recurrence were determined, MATERIAL AND METHODS: We investigated the
      presence of p53 mutations in primary tumor samples and in the surgical margins of
      34 patients with head and neck cancer using single strand conformational
      polymorphism and sequencing analysis. RESULTS: The p53 mutations (codons
      175addAT, 175delGC, 206G --> A, and 248delC) were found in the primary tumor
      samples of 15 of 34 patients (44.12%) and in the surgical margins of 5 of the 15
      tumors (33.33%) with p53 mutations. CONCLUSIONS: We found no statistically
      significant association between the presence of p53 mutations in the primary
      tumor, the clinical and pathological features, or outcome of head and neck
      squamous cell carcinoma in this study. Furthermore, the presence of p53 mutations
      in the surgical margins may not increase the risk of local-regional recurrence,
      but probably increases the risk of developing distant metastases or second
      primary tumors.

PMID- 17557567
TI  - The expression of metallothioneins on imprint smears of prostate carcinoma:
      correlation with clinicopathologic parameters and tumor proliferative capacity.
AB  - AIMS AND BACKGROUND: Metallothioneins are a family of metalbinding cysteine-rich
      proteins that play an important role in cellular processes such as proliferation
      and apoptosis, protection against oxidative stress and metal ion homeostasis and
      detoxification. Recent findings suggest that metallothioneins might play a
      significant role in the development and progression of prostate cancer. It has
      been also demonstrated that Ki67 expression may have prognostic value for disease
      free survival in cases of prostate carcinoma. STUDY DESIGN: Imprint smears
      samples obtained from 70 patients immediately after radical prostatectomy for
      prostatic carcinoma were immunostained with monoclonal antibodies against
      metallothioneins and Ki-67. Metallothionein expression was correlated with Ki-67
      immunostaining, Gleason score, stage, preoperative prostate-specific antigen
      levels and biochemical recurrence. RESULTS: Metallothionein expression was shown
      to correlate strongly with Gleason score (P < 0.001) and significantly with
      pathological staging and Ki-67 immunostaining (P < 0.001, P < 0.05,
      respectively). In contrast, no significant association between metallothioneins
      and preoperative PSA was demonstrated. Both of the studied markers
      (metallothioneins and Ki-67) correlated with recurrence (P = 0.009, P = 0.006,
      respectively). CONCLUSIONS: The present findings support the independent
      predictive value of metallothioneins and Ki-67 in prostate cancer. However,
      additional data are needed in order to reveal the factors that influence the
      expression of metallothioneins in epithelial neoplastic cells and clarify their
      mechanism of action.

PMID- 17557568
TI  - Mutational analysis of the BH3 domains of proapoptotic Bcl-2 family genes Bad,
      Bmf and Bcl-G in laryngeal squamous cell carcinomas.
AB  - AIMS: There is mounting evidence that deregulation of apoptosis is involved in
      the mechanisms of cancer development. Somatic mutations of apoptosis-related
      genes have been reported in many human cancers. The aim of this study was to
      explore the possibility that mutation of the BH3 domains of the proapoptotic Bcl
      2 genes Bad, Bmf and Bcl-G might be involved in the development of laryngeal
      cancer. METHODS: We analyzed the BH3 domains of Bad, Bmf and Bcl-G for the
      detection of somatic mutations in 33 squamous cell carcinomas of the larynx by a
      polymerase chain reaction-based single-strand conformation polymorphism assay.
      RESULTS: There were no somatic mutations of the BH3 domains of Bad, Bmfand BcI-G
      in the laryngeal squamous cell carcinoma samples. CONCLUSIONS: The data presented
      here indicate that BH3 domain mutation of the proapoptotic genes Bad, Bmf and Bcl
      G is rare in laryngeal squamous cell carcinoma and may not contribute to the
      apoptosis-resistance mechanisms of laryngeal squamous cell carcinoma.

PMID- 17557569
TI  - Mediastinal thymolipoma: a rare occurrence with striated myoid cells.
AB  - We describe a 49-year-old man who presented to hospital with unstable angina and
      who underwent emergency coronary artery bypass grafting. During the surgical
      procedure, an incidental anterior mediastinal mass was discovered. Histological
      examination of this mediastinal mass revealed a thymolipoma containing numerous
      polygonal, striated myoid cells that were immunoreactive for desmin, muscle
      specific actin and myoglobin. Electron microscopy demonstrated numerous Z band
      structures confirming myoid differentiation. Even though the appearance of myoid
      cells in thymolipoma may be alarming, this tumor should be recognized as a benign
      entity. Thymolipomas containing striated myoid cells should be differentiated
      from more ominous thymic neoplasms, including teratomas and thymic liposarcomas.
      To our knowledge, this is only the third reported case of thymolipoma containing
      striated myoid cells.

PMID- 17557570
TI  - Renal cell cancer and sorafenib: skin toxicity and treatment outcome.
AB  - We describe the case of a young man with refractory renal cell carcinoma who
      achieved an objective response in a metastatic lesion after biotherapy with the
      multikinase inhibitor sorafenib and also developed a severe skin reaction. The
      patient had been previously treated with various combinations of
      immunochemotherapy without any clinical benefit. We performed a brief review of
      the literature where similar cases were documented with the use of various anti
      EGFR agents. The hypothesis of the correlation of skin toxicity with disease
      response is not new, but in the absence of any strong evidence remains
      controversial.

PMID- 17557571
TI  - Lack of cardiotoxicity with liposomal doxorubicin in an elderly case of ovarian
      cancer.
AB  - Ovarian cancer is typically a disease of elderly women, usually occurring after
      menopause with a peak incidence in the eighth decade of life. Elderly patients
      are more likely to suffer the adverse effects of chemotherapy, which may
      influence successive lines of treatment. We describe the case of an elderly woman
      with platinum-sensitive ovarian cancer treated with several lines of chemotherapy
      who developed acute cardiogenic pulmonary edema with her first line of therapy,
      which included paclitaxel, and her fourth line containing gemcitabine. However, a
      complete regimen of pegylated liposomal doxorubicin in association with
      oxaliplatin was well tolerated. Other authors have reported absence of
      cardiotoxicity with liposomal doxorubicin in their study populations, but no
      mention was made of patients with a known prior susceptibility to transient heart
      failure when treated with other chemotherapeutic agents. Our case provides
      evidence that even in these more difficult-to-treat cases, where cumulative
      cardiotoxicity may be relatively unpredictable, liposomal doxorubicin does not
      affect cardiac function.

PMID- 17557572
TI  - Wernicke's encephalopathy after allogeneic stem cell transplantation.
AB  - Wernicke's encephalopathy is an acute neuropsychiatric condition due to thiamine
      deficiency frequently associated with chronic alcohol abuse. We describe 2 cases
      of patients who experienced acute Wernicke's encephalopathy after allogeneic stem
      cell transplantation associated with the use of commercial total parental
      nutrition. Early diagnosis with magnetic resonance imaging and timely treatment
      with thiamine resulted in rapid resolution of clinical and radiological signs. In
      conclusion, the prolonged use of commercial total parental nutrition formulas
      must be supplemented with thiamine in the form of intramuscularly administered
      multivitamins.

PMID- 17557573
TI  - Ewing's sarcoma of the third metatarsal: a case report and review of the
      literature.
AB  - We report a rare case of Ewing's sarcoma involving the third metatarsal bone and
      spreading into adjacent bone in a 23-year-old man, with special emphasis on
      imaging characteristics. On radiographs the tumor presented as a permeative lytic
      lesion with aggressive periosteal reaction and cortical destruction. Computed
      tomography and magnetic resonance imaging delineated the osseous and soft tissue
      extent of the tumor. A large soft-tissue mass around the involved bone was highly
      indicative of Ewing's sarcoma. Cortical invasion of the neighboring second
      metatarsal was seen only on magnetic resonance imaging. Increased up-take of
      technetium 99m methylene diphosphonate was noticed on bone scintigraphy. An early
      diagnosis of Ewing's sarcoma, even when it occurs in unusual locations, is
      necessary for adequate treatment and is of particular importance in terms of
      prognosis. The optimal imaging modality for the diagnosis of Ewing's sarcoma is
      magnetic resonance imaging since it allows accurate analysis of the soft-tissue
      component and visualization of possible local invasion of adjacent structures.

PMID- 17557574
TI  - Primary osteosarcoma of the kidney with retroperitoneal hemorrhage. Case report
      and review of the literature.
AB  - Primary osteosarcoma of the kidney is a very rare neoplasm with a very poor
      prognosis and unclear histogenesis. Only 20 cases have been reported in the
      literature. It has a strong tendency to recur locally and spread to distant
      sites. We present the clinical case of a 79-year-old man affected by a primary
      osteosarcoma of the kidney presenting with substantial retroperitoneal tumor
      hemorrhage. Laparotomy revealed a massive retroperitoneal hematoma due to a
      bleeding large stony renal mass with multiple bizarre calcifications. The
      diagnosis of primary renal osteosarcoma was made on the basis of hematoxylin
      eosin staining and confirmed by electron microscopy. Hematoma drainage and
      radical nephrectomy were performed. To our knowledge this is the first case of
      bleeding renal osteosarcoma reported in the literature. The most important
      clinical findings, the pathogenesis and the treatment modalities of this rare
      neoplasm are discussed.

PMID- 17557575
TI  - Gastric cancer metastatic to the pituitary gland: a case report.
AB  - Neoplasms from almost every tissue have been reported to metastasize to the
      pituitary. Gastric carcinoma is a rare cause of metastases in pituitary gland.
      Gastric carcinoma will be the primary tumor in less than 2% of patients with
      pituitary gland metastases. We report the case of a 60-years old white man with
      liver metastasis from gastric cancer with fair presentation symptoms of pituitary
      gland metastasis. Basal endocrinological work-up showed corticotroph,
      gonadotroph, somatotroph and thyrotroph cell insufficiency; serum PRL was
      elevated and no deficit of the ADH level was observed. Despite the hormonal
      deficits the patient did not report any specific symptom. After diagnosis the
      patient began thyroid and adrenal-replacement therapy and was referred to
      Radiotherapy Unit for treatment on the sellar and pituitary gland region.

PMID- 17557576
TI  - Myoepithelial hamartoma of the stomach simulating a gastric carcinoma. A case
      report.
AB  - Myoepithelial hamartoma is a very rare submucosal tumor of the stomach. Magnus
      Alsleben first described 5 cases of this tumor in 1903. More recently (1993)
      Vandelli et al. published a review of the literature comprising only 33 cases.
      Histologically, the tumor is characterized by hypertrophic smooth muscle bands
      surrounding diverse epithelial elements that can be arranged in different ways:
      as a simple glandular structure, Brunner's gland, pancreatic ducts and
      occasionally pancreatic acinus. We report a case of myoepithelial hamartoma of
      the stomach simulating a gastric carcinoma.

PMID- 17557577
TI  - Adult-type granulosa cell tumor of the testis. Report of a case.
AB  - A new case of adult-type granulosa cell tumor of the testis in a 77-year-old man
      is reported. The patient was healthy and asymptomatic and only showed a discrete
      left hydrocele. The orchiectomy specimen showed the typical histology of this
      entity, with prominent nuclear grooving and Call-Exner-like bodies as the main
      features. The literature on this exceedingly rare tumor in the testis is reviewed
      and briefly commented upon.

PMID- 17557578
TI  - Synchronous bilateral breast cancer in men: a case report and review of the
      literature.
AB  - Breast carcinoma is a rare disease in men, and bilateral cases are extremely
      uncommon. The rarity of male breast carcinoma and the small number of large
      studies on this topic have made it necessary to extrapolate treatment standards
      and outcomes from those established for women. Between 1997 and 2007, 75 men with
      breast cancer were referred to our institute, and the bilateral case we present
      here was the only one we have observed since 1994. The goal of our work was to
      contribute to the available literature with this extremely unusual presentation
      of the disease.

PMID- 17557579
TI  - Big tobacco and moto-GP: why no warnings on the motorcycles?

PMID- 17557580
TI  - Imatinib mesylate treatment in a patient with chemoresistant Ph+ acute myeloid
      leukemia: possible role of Wilms' tumor gene 1.

PMID- 17557581
TI  - Radiation injury to blood vessels.

PMID- 17557582
TI  - Use of probiotics for prevention of radiation-induced diarrhea.

PMID- 17557584
TI  - [Optimization of treatment options through a multidisciplinary approach for
      advanced hormone refractory prostate carcinoma].

PMID- 17557583
TI  - [An update on the role of PSA and it's meaning in a hormone refractory patient].

PMID- 17557585
TI  - [Reports from the ASCO GI 2007, Gastrointestinal Cancers Symposium, Orlando,
      Florida].

PMID- 17557586
TI  - The role of first- and second-order stimulus features for human overt attention.
AB  - When processing complex visual input, human observers sequentially allocate their
      attention to different subsets of the stimulus. What are the mechanisms and
      strategies that guide this selection process? We investigated the influence of
      various stimulus features on human overt attention--that is, attention related to
      shifts of gaze with natural color images and modified versions thereof. Our
      experimental modifications, systematic changes of hue across the entire image,
      influenced only the global appearance of the stimuli, leaving the local features
      under investigation unaffected. We demonstrated that these modifications
      consistently reduce the subjective interpretation of a stimulus as "natural"
      across observers. By analyzing fixations, we found that first-order features,
      such as luminance contrast, saturation, and color contrast along either of the
      cardinal axes, correlated to overt attention in the modified images. In contrast,
      no such correlation was found in unmodified outdoor images. Second-order
      luminance contrast ("texture contrast") correlated to overt attention in all
      conditions. However, although none of the second-order color contrasts were
      correlated to overt attention in unmodified images, one of the second-order color
      contrasts did exhibit a significant correlation in the modified images. These
      findings imply, on the one hand, that higher-order bottom-up effects--namely,
      those of second-order luminance contrast--may partially account for human overt
      attention. On the other hand, these results also demonstrate that global image
      properties, which correlate to the subjective impression of a scene being
      "natural," affect the guidance of human overt attention.

PMID- 17557587
TI  - Overriding auditory attentional capture.
AB  - Attentional capture by color singletons during shape search can be eliminated
      when the target is not a feature singleton (Bacon & Egeth, 1994). This suggests
      that a "singleton detection" search strategy must be adopted for attentional
      capture to occur. Here we find similar effects on auditory attentional capture.
      Irrelevant high-intensity singletons interfered with an auditory search task when
      the target itself was also a feature singleton. However, singleton interference
      was eliminated when the target was not a singleton (i.e., when nontargets were
      made heterogeneous, or when more than one target sound was presented). These
      results suggest that auditory attentional capture depends on the observer's
      attentional set, as does visual attentional capture. The suggestion that hearing
      might act as an early warning system that would always be tuned to unexpected
      unique stimuli must therefore be modified to accommodate these strategy-dependent
      capture effects.

PMID- 17557588
TI  - Tracking unique objects.
AB  - Is content addressable in the representation that subserves performance in
      multiple-object-tracking (MOT) experiments? We devised an MOT variant that
      featured unique, nameable objects (cartoon animals) as stimuli. There were two
      possible response modes: standard, in which observers were asked to report the
      locations of all target items, and specific, in which observers had to report the
      location of a particular object (e.g., "Where is the zebra?"). A measure of
      capacity derived from accuracy allowed for comparisons of the results between
      conditions. We found that capacity in the specific condition (1.4 to 2.6 items
      across several experiments) was always reliably lower than capacity in the
      standard condition (2.3 to 3.4 items). Observers could locate specific objects,
      indicating a content-addressable representation. However, capacity differences
      between conditions, as well as differing responses to the experimental
      manipulations, suggest that there may be two separate systems involved in
      tracking, one carrying only positional information, and one carrying identity
      information as well.

PMID- 17557589
TI  - Age-related changes in discrimination of unfamiliar odors.
AB  - If odor perception involves mnemonic processes, differences in olfactory
      experience should affect discriminative ability. This was examined here by
      comparing discriminative performance in children and adults. Using an oddity test
      of discrimination, in Experiment 1 we tested 6-year-olds (G1), 11-year-olds (G6),
      and adults (A) on their ability to discriminate unfamiliar odors that varied
      either in quality (Q) or in quality and intensity (QI). G1 participants were
      poorer at discriminating the QI set, relative to G6 and A. In Experiment 2, we
      used an analogous visual procedure and confirmed that this age-related difference
      was olfactory specific. In Experiment 3, we repeated Experiment 1 but used an
      articulatory suppression task. G1 participants were poorer than G6 and A
      participants for both the Q and the QI sets. The implications of these findings
      for experiential accounts of odor perception and olfactory working memory are
      discussed.

PMID- 17557590
TI  - Oscillatory priming and form complexity.
AB  - Detection of a target grouping is expedited when the target display is preceded
      by presentation of an oscillating premask that includes priming elements
      presented intraphasically and below detection threshold at the display locations
      subsequently occupied by the target. Five experiments were performed to
      investigate how priming is affected by both the complexity and the geometry of
      prime/target forms. Experiment 1 showed that the subjective complexity of
      different polygons was coded in accord with an objective measure of form
      complexity. Experiments 2 and 3 revealed oscillatory priming to increase as a
      function of the subjective complexity of prime/target forms when those forms were
      regular and predictable. However, Experiments 4 and 5 showed that this relation
      did not hold when the prime/target forms were irregular and unpredictable. Taken
      together, it is argued that both subjective complexity and the Pragnanz quality
      of the prime/target forms come to determine the magnitude of priming. These
      results are discussed with reference to current physiological hypotheses
      regarding perceptual organization.

PMID- 17557591
TI  - Attentional templates regulate competitive interactions among attended visual
      objects.
AB  - In two experiments, we examined the mechanisms responsible for creating a zone of
      interference surrounding an attended visual object (see, e.g., Mounts & Gavett,
      2004). In Experiment 1, the similarity between attended stimuli and noise items
      was manipulated in order to contrast an account based on competitive interactions
      between attended items with an account based on inefficient filtering of
      unattended stimuli. Consistent with the competitive interaction account, the data
      revealed that similarity between attended items increased the strength of
      localized interference, whereas similarity of noise items to the attended stimuli
      did not. Experiment 2 showed that the interference observed between attended
      items was determined by their match to attentional templates.

PMID- 17557592
TI  - Discriminating languages by speech-reading.
AB  - The goal of this study was to explore the ability to discriminate languages using
      the visual correlates of speech (i.e., speech-reading). Participants were
      presented with silent video clips of an actor pronouncing two sentences (in
      Catalan and/or Spanish) and were asked to judge whether the sentences were in the
      same language or in different languages. Our results established that Spanish
      Catalan bilingual speakers could discriminate running speech from their two
      languages on the basis of visual cues alone (Experiment 1). However, we found
      that this ability was critically restricted by linguistic experience, since
      Italian and English speakers who were unfamiliar with the test languages could
      not successfully discriminate the stimuli (Experiment 2). A test of Spanish
      monolingual speakers revealed that knowledge of only one of the two test
      languages was sufficient to achieve the discrimination, although at a lower level
      of accuracy than that seen in bilingual speakers (Experiment 3). Finally, we
      evaluated the ability to identify the language by speech-reading particularly
      distinctive words (Experiment 4). The results obtained are in accord with recent
      proposals arguing that the visual speech signal is rich in informational content,
      above and beyond what traditional accounts based solely on visemic confusion
      matrices would predict.

PMID- 17557593
TI  - Gain control in the auditory system: absolute identification of intensity within
      and across the two ears.
AB  - A number of studies have suggested that the auditory system employs nonlinear
      gain control to modulate its response to a broad range of stimulus intensities
      (e.g., Parker, Murphy, & Schneider, 2002), but the precise location and nature of
      this mechanism remains uncertain. To address these issues, we investigated the
      extent to which gain control in one ear was influenced by auditory events in the
      other ear. Listeners were asked to identify which of four sounds, varying in
      intensity (25, 30, 35, and 40 dB [SPL]), had been presented to the left ear.
      Subsequent test sets included an 80-dB (SPL) stimulus presented to either the
      left (ipsilateral) or the right (contralateral) ear. Ipsilateral presentations of
      the 80-dB (SPL) stimulus produced a greater reduction in identification accuracy
      among the original four sounds than did contralateral presentations, but both
      presentations caused a reduction in gain. In a second experiment, the perceived
      laterality of a sound was manipulated by presenting the same sound to both ears
      with an interaural time delay. When the 80-dB (SPL) stimulus was added to the set
      of quiet sounds (which were presented to both ears but were perceived to be in
      the left ear because of the interaural time delay), identification accuracy was
      reduced by the same amount, independently of whether the 80-dB (SPL) stimulus was
      perceived only in the ipsilateral ear or only in the contralateral ear.

PMID- 17557594
TI  - Kinematic cues for person identification from biological motion.
AB  - We examined the role of kinematic information for person identification.
      Observers learned to name seven walkers shown as point-light displays that were
      normalized by their size, shape, and gait frequency under a frontal, half
      profile, or profile view. In two experiments, we analyzed the impact of
      individual harmonics as created by a Fourier analysis of a walking pattern, as
      well as the relative importance of the amplitude and the phase spectra in walkers
      shown from different viewpoints. The first harmonic contained most of the
      individual information, but performance was also above chance level when only the
      second harmonic was available. Normalization of the amplitude of a walking
      pattern resulted in a severe deterioration of performance, whereas the relative
      phase of the point lights was only used from a frontal viewpoint. No overall
      advantage for a single learning viewpoint was found, and there is considerable
      generalization to novel testing viewpoints.

PMID- 17557595
TI  - Small-sample characterization of stochastic approximation staircases in forced
      choice adaptive threshold estimation.
AB  - Despite the widespread use of up-down staircases in adaptive threshold
      estimation, their efficiency and usability in forced-choice experiments has been
      recently debated. In this study, simulation techniques were used to determine the
      small-sample convergence properties of stochastic approximation (SA) staircases
      as a function of several experimental parameters. We found that satisfying some
      general requirements (use of the accelerated SA algorithm, clear suprathreshold
      initial stimulus intensity, large initial step size) the convergence was accurate
      independently of the spread of the underlying psychometric function. SA
      staircases were also reliable for targeting percent-correct levels far from the
      midpoint of the psychometric function and performed better than classical up-down
      staircases with fixed step size. These results prompt the utilization of SA
      staircases in practical forced-choice estimation of sensory thresholds.

PMID- 17557596
TI  - Testing models of object substitution with backward masking.
AB  - A briefly presented visual target stimulus can be difficult to identify if shown
      in the context of a mask stimulus. There are several quantitative models that
      have been used to explain many different masking effects. Here, we look at
      modeling what has been called object substitution. We analyze four models and
      show that three of the models work with a common principle, whereas the fourth
      behaves quite differently. The three similar models have previously been used to
      explain many other aspects of visual masking, whereas the fourth model was
      designed exclusively to deal with object substitution masking effects. We
      identify an experimental test on the basis of which to choose between the models.
      The experimental results support the behavior of the fourth model.

PMID- 17557597
TI  - Haptic parallelity perception on the frontoparallel plane: the involvement of
      reference frames.
AB  - It has been established that spatial representation in the haptic modality is
      subject to systematic distortions. In this study, the haptic perception of
      parallelity on the frontoparallel plane was investigated in a bimanual matching
      paradigm. Eight reference orientations and 23 combinations of stimulus locations
      were used. The current hypothesis from studies conducted on the horizontal and
      midsagittal planes presupposes that what is haptically perceived as parallel is a
      product of weighted contributions from both egocentric and allocentric reference
      frames. In our study, we assessed a correlation between deviations from the
      veridical and hand/arm postures and found support for the role of an intermediate
      frame of reference in modulating haptic parallelity on the frontoparallel plane
      as well. Moreover, a subject-dependent biasing influence of the egocentric
      reference frame determines both the reversal of the oblique effect and a scaling
      effect in deviations as a function of bar position.

PMID- 17557598
TI  - Deriving auditory features from triadic comparisons.
AB  - A feature-based representation of auditory stimuli is proposed and tested
      experimentally. Within a measurement-theoretical framework, it is possible to
      decide whether a representation of subjective judgments with a set of auditory
      features is possible and how unique such a representation is. Furthermore, the
      method avoids confounding listeners' perceptual and verbal abilities, in that it
      strictly separates the process of identifying auditory features from labeling
      them. The approach was applied to simple synthetic sounds with well-defined
      physical properties (narrow-band noises and complex tones). For each stimulus
      triad, listeners had to judge whether the first two sounds displayed a common
      feature that was not shared by the third, by responding with a simple "yes" or
      "no." Because of the high degree of consistency in the responses, feature
      structures could be obtained for most of the subjects. In summary, the proposed
      procedure constitutes a supplement to the arsenal of psychometric methods with
      the main focus of identifying the type of sensation itself, rather than of
      measuring its threshold or magnitude.

PMID- 17557599
TI  - The influence of synchronous audiovisual distractors on audiovisual temporal
      order judgments.
AB  - Participants made unspeeded temporal order judgments (TOJs) regarding which
      occurred first, anauditory or a visual target stimulus, when they were presented
      at a variety of different stimulus onset asynchronies. The target stimuli were
      presented either in isolation or positioned randomly among a stream of three
      synchronous audiovisual distractors. The largest just noticeable differences were
      reported when the targets were presented in the middle of the distractor stream.
      When the targets were presented at the beginning of the stream, performance was
      no worse than when the audiovisual targets were presented in isolation.
      Subsequent experiments revealed that performance improved somewhat when the
      position of the target was fixed or when the target was made physically
      distinctive from the distractors. These results show that audiovisual TOJs are
      impaired by the presence of audiovisual distractors and that this cost can be
      ameliorated by directing attention to the appropriate temporal position within
      the stimulus stream.

PMID- 17557600
TI  - Awareness of body weight status among family medicine clinic patients.
AB  - OBJECTIVES: a) determine the prevalence of accurate perceptions of body weight
      status; b) assess awareness of risk and willingness to change; c) assess
      physicians' documentation of a weight problem. DESIGN: cross-sectional survey of
      356 clinic patients. MEASURES: patient questionnaire; data extracted from charts.
      RESULTS: BMI averaged 34 for females, 31 for males. Twenty-five percent were
      overweight, 35% obese and 22% morbidly obese. Fifty-seven percent underestimated
      their weight status. Most obese and morbidly obese patients recognized the
      increased risk and wanted to change. Only the overweight patients who were
      accurate considered themselves at risk and wanted to change. Only 17% of office
      charts included the weight problem in the cumulative problem list. CONCLUSION:
      Despite the high prevalence of inaccurate perception of weight status, most
      patients were aware of risk and willing to change, except for the overweight
      patients. This subgroup would be a good target for an intervention to increase
      awareness.

PMID- 17557601
TI  - Update on hantavirus in Oklahoma: are we missing cases?
AB  - Hantavirus Pulmonary Syndrome (HPS) was first recognized in 1993. Through July 6,
      2005, 396 cases have been reported in the US, including 50 from Kansas, Texas,
      and Oklahoma. We report the second case of HPS in Oklahoma and present data from
      rodent testing to support the presence of hantaviruses across Oklahoma. We
      examined Oklahoma death certificates for 1999-2003 for possible unreported HPS
      cases. The rate of death in young adults 15-49 years due to acute respiratory
      distress syndrome was 69% higher and the death rate due to unspecified
      respiratory failure was three times higher in the grassland area of Oklahoma as
      compared to the non-grassland. It appears the highest risk of HPS is in the
      Oklahoma grasslands but Sin Nombre virus is present in the non-grassland area as
      well. We request physician collaboration in detection and reporting of HPS cases
      and present brief recommendations for prevention.

PMID- 17557602
TI  - Part IX. Quinolone antimicrobials.

PMID- 17557603
TI  - Four personalities who defined a decade of health service reforms.

PMID- 17557604
TI  - 'Clinical opinion has always determined who is treated'.

PMID- 17557605
TI  - 'Much more research is needed before we write off community matrons'.

PMID- 17557606
TI  - Reducing doctors' hours. What it means for you.

PMID- 17557607
TI  - Fighting heart disease at home.

PMID- 17557608
TI  - Improving patients' privacy and dignity on mixed-sex wards.

PMID- 17557609
TI  - The endocrine system. Part One. The endocrine system, pituitary and hypothalamus
      glands.

PMID- 17557610
TI  - Caring for patients who experience hallucinations.
AB  - This article examines the incidence and causes of hallucinations, as well as
      detailing the different types of hallucinations. It also describes the nurse's
      role when caring for a patient who is experiencing hallucinations.

PMID- 17557611
TI  - 'Fear of making mistakes can become disabling'.

PMID- 17557612
TI  - [Influence of local anaesthesia on short- and long-term pain induced in calves by
      three bloodless castration methods].
AB  - Behavioural and cortisol responses of calves were used as indicators of pain to
      assess short- and long-term effects of three bloodless castration methods with
      and without local anaesthesia. Eighty calves, aged 21 to 28 days, were control
      handled (20) or castrated by Burdizzo (25), rubber ring (25), or crushing
      technique (10). Either a total volume of 10 ml of Lidocaine or NaCl was
      distributed in both spermatic cords and the scrotal neck. The plasma cortisol
      response was monitored for 72 hours, and behavioural and clinical traits over a
      three-month period. Castration success was assessed by degree of atrophy and
      histological tissue examination. The crushing technique cannot be recommended due
      to incomplete castration success, and the evaluation was stopped after 10
      animals. Local anaesthesia reduced the level of indicators of acute pain after
      Burdizzo and rubber ring technique. It did, however, not result in a totally
      painless castration. When castration is performed at the age of 3 to 4 weeks, the
      rubber ring but not the Burdizzo method showed evidence of chronic pain lasting
      for several weeks.

PMID- 17557613
TI  - [Influence of local anaesthesia on pain and distress induced by bloodless
      castration methods in young lambs].
AB  - Behavioural and cortisol responses of lambs were used as indicators of pain and
      distress to assess short- and long-term effects of bloodless castration methods
      with and without local anaesthesia. Eighty lambs, aged 2-7 days, were control
      handled or castrated by crushing- Burdizzo- or rubber ring method with and
      without local anaesthesia. Either 4 mg/kg diluted lidocaine, or corresponding
      volumes of physiologic sodium chloride solution were distributed in both
      spermatic cords and the scrotal neck. The serum cortisol response was monitored
      for 48 h, behavioural- and clinical traits over a 3-month period. The crushing
      castration method was excluded from the study after 10 lambs had been castrated,
      since this method showed severe local reactions. Local anaesthesia significantly
      reduced behavioural and cortisol responses after rubber ring castration and
      tendentially after Burdizzo castration. Prolonged or chronic pain after rubber
      ring castration with anaesthesia was not evident. If combined with local
      anaesthesia, both the rubber ring and the Burdizzo method are acceptable methods
      for castration of lambs up to one week of age.

PMID- 17557614
TI  - Karyotype evaluation among young horse populations in Poland.
AB  - Five hundred young horses of the following breeds: Thoroughbred, Silesian,
      Malopolska, Wielkopolska, Polish Konik, Hutsul, Shetland Pony, Half-bred Anglo
      Arabian, Noble Half-bred, Fjord and crosses were cytogenetically investigated.
      Chromosome preparations obtained after lymphocyte culture were analysed using
      conventional Giemsa staining and CBG-banding methods. In the case of
      abnormalities GTG-banding as well as FISH technique were applied. In ten mares
      different karyotypic abnormalities were diagnosed. One mare showed chromosome
      chimerism (64,XX/64,XY), eight had sex chromosomal aneuploidy (one in pure line
      63,X and seven in mosaic form 63,X/64,XX) and one presented autosomal aneuploidy
      with mosaicism (64,XX/65,XX,+31). The influence of sex chromosome abnormalities
      on fertility and the possible utilisation of karyotypic control in any selection
      programme are discussed.

PMID- 17557615
TI  - [Family oriented case management].

PMID- 17557616
TI  - [Family caregiver education and nursing support team].

PMID- 17557617
TI  - [The captain surrenders his flagship].

PMID- 17557618
TI  - [New standard of responsibility].

PMID- 17557619
TI  - [Integration instead of exclusion].

PMID- 17557620
TI  - [Detrimental uncertainty].

PMID- 17557621
TI  - [A question of trust].

PMID- 17557622
TI  - [Knowledge transfer: challenge of a special sort].

PMID- 17557623
TI  - [Caution with the word "overextended" (2)].

PMID- 17557624
TI  - [The family in transition].

PMID- 17557625
TI  - [Specific nursing education is requested].

PMID- 17557626
TI  - [Binge drinking in adolescents: how to help?].

PMID- 17557627
TI  - [An immense European building project].

PMID- 17557628
TI  - [School nurse: an easy job in your opinion?].

PMID- 17557629
TI  - Global advanced practice nursing: how practice developments and professional
      organizational initiatives might influence educational developments.

PMID- 17557630
TI  - Lin.

PMID- 17557631
TI  - And a-traveling I will go....

PMID- 17557632
TI  - Integration of global health concepts in nursing curricula: a national study.
AB  - The concept of global health is evolving with a growing recognition that
      international social, political, economic, environmental, and cultural issues
      affect health and health care around the world. Nurse faculty are challenged to
      find ways to prepare future nurses to provide care in an environment that is
      increasingly affected by globalization. This article presents results of a
      national survey of schools of nursing designed to identify a consensus definition
      for global health, attributes of the concept, and ways in which global health is
      identified and addressed in nursing curricula. Attributes of global health
      identified in this study are congruent with the literature. Implications for
      educators are presented, along with examples of how technology can be used to
      facilitate global interactions.

PMID- 17557633
TI  - Using a capstone cultural diversity paper for program outcomes evaluation.
AB  - The need to evaluate program outcomes is a task facing many nurse faculty. This
      three-part capstone paper is used to evaluate the baccalaureate program outcomes
      of critical thinking, written communication, and therapeutic interventions.
      First, students interview clients from other cultures, religions, or sexual
      orientations. Second, students analyze the interview data and compare their
      findings with the literature. Third, students reflect on their own cultural
      beliefs and values and discuss their influence on future nursing practice. The
      development of a grading rubric, levels of achievement, outcomes, program
      revisions, and student comments are discussed.

PMID- 17557634
TI  - The educational preparation: of nurses in Ireland.
AB  - The history and evolution of nurse education in Ireland has been similar to that
      of other countries. Initially conducted under the apprenticeship model
      established by Nightingale, it continued under this model for more than a century
      because the educational needs of nurses were seen as subordinate to the needs of
      the health service. The necessity for reform in nursing education was identified
      in a number of Irish government policy documents. One of the strongest arguments
      put forward for the future educational preparation of nurses stemmed from the
      Report of the Commission on Nursing in 1998. The recommendations of the report,
      implemented with the launch of the preregistration nursing degree program in
      2002, set the stage for a new era in the education of nurses.

PMID- 17557635
TI  - Developing a culturally competent health care workforce in Japan: implications
      for education.
AB  - In recent years, the population of foreign nationals and individuals from diverse
      cultural, racial, ethnic, and linguistic populations has consistently increased
      in Japan. An apparent failure by the health care workforce to deliver culturally
      congruent health care services has resulted in dissatisfaction with the health
      care system on the part of foreign nationals and increased potential for negative
      health care outcomes. Primary hindrances to the development of a culturally
      competent health care workforce include limited exposure to foreigners, cultural
      factors, and language difficulties. Recommendations are proposed for strategic
      educational actions to address these obstacles and develop in Japan a culturally
      competent health care workforce.

PMID- 17557636
TI  - The influence of culture on clinical nurses transitioning into the faculty role.
AB  - The purpose of this qualitative study was to describe how cultural differences
      and similarities affect the transition of nurses into the faculty role from
      professional clinical practice. Components of culture (e.g., values and beliefs)
      of seven nurses new to the faculty role were examined using multiple methods of
      document review, interviews, and observations. Results demonstrated that cultural
      dissonance creates conflict in new nurse faculty as the values they bring from
      clinical practice influence their transition into academe. Cultural dissonance
      can be improved through formal education, mentoring, and socialization to the
      faculty role. It recommended that schools of nursing adopt the values inherent in
      the nursing profession.

PMID- 17557637
TI  - Promoting smoking cessation among nursing students: how faculty can help.
AB  - Cigarette smoking is a major health issue in the United States. Research has
      shown that more than a quarter of young adults aged 18-24 are smokers, and there
      has been a recent rise in the prevalence of cigarette smoking among college
      students. Many researchers have investigated smoking among nursing students, in
      the United States and worldwide. This article provides an overview of these
      research findings and a discussion of interventions that may help promote smoking
      cessation. Nurse faculty are encouraged to take a lead in smoking cessation
      efforts.

PMID- 17557638
TI  - Nursing education 2.0: second life.

PMID- 17557639
TI  - Introducing the NLN/Carnegie National Survey of Nurse Educators: compensation,
      workload, and teaching practice.

PMID- 17557640
TI  - Advancing the science of nursing education: more findings from the National
      Survey on Excellence in Nursing education.

PMID- 17557641
TI  - The contributions of a nursing student: priceless.

PMID- 17557642
TI  - [Marginal accuracy of pressed ceramic full veneers with different preparation
      techniques before and after simulated jaw movement].
AB  - This in-vitro study investigated the marginal accuracy of press-ceramic full
      veneers with different preparation designs. Measurements of the marginal gap were
      performed after adhesive cementation as well as after mouth motion fatigue of the
      veneers. 64 extracted human maxillary central incisors were divided into four
      groups of 16 specimens each and prepared as follows: Group SZ = enamel (S)
      restricted 0.5 mm deep preparation with a high palatal shoulder (contact point on
      tooth structure [Z]), Group SK = enamel (S) restricted 0.5 mm deep preparation
      with a low palatal shoulder (contact point on ceramic [K]), Group DZ = dentine
      (D) included 1 mm deep preparation with a high palatal shoulder (contact point on
      tooth structure), Group DK = dentine included 1 mm deep preparation with a low
      palatal shoulder (contact point on ceramic). IPS e.max Press ceramic was used to
      fabricate the full veneers. Restorations were adhesively luted with a dual
      polymerizing resin-cementVariolinkII* (*Ivoclar-Vivadent AG). Specimens underwent
      fatigue in a masticatory simulator (1.2 million cycles; 49 N), including thermal
      cycling (5500; 5 degrees C/55 degrees C). Computer-aided measurements of the
      marginal accuracy using stereo-light-microscopy (200x) resulted in mean values of
      56 pm to 64 pm after adhesive luting. Masticatory simulation did not cause
      significant changes of mean marginal accuracies. In comparison, neither the
      adhesive cementation of the veneers to mainly enamel or dentin nor the position
      of load application did demonstrate a significant influence on the marginal fit
      in the given investigation period. Based on the used measurement methods, mouth
      motion fatigue of the restorations did not demonstrate a significant change of
      marginal fit.

PMID- 17557643
TI  - [Esthetic and technical aspects of conventional removable dentures. Design of a
      complete denture in the upper jaw and a telescopic denture in the lower jaw. A
      case report].
AB  - Removable partial dentures and complete dentures are still an important part of
      the daily prosthetic work of dentists and dental technicians. Thereby the
      esthetic design of conventional fixed restorations is challenging the dentist and
      the dental technician in removable prosthodontics. The result is mainly
      influenced by the clinical and technical procedure as well as by the choice of
      material. In this article, the reconstruction of a patient with a complete
      removable dental prosthesis in the upper jaw and an overlay denture on four
      telescopes in the lower jaw is presented.

PMID- 17557644
TI  - [Therapy of recurrent fixed anterior TMJ dislocation with mini-plates in an aged
      patient with other ailments. A case report].
AB  - Unilateral or bilateral dislocation of the TMJ is frequent. Usually it can be
      treated by the method described by Hippocrates. If conservative treatment (splint
      therapy, biofeedback, etc.) does not succeed related to recurrent fixed TMJ
      dislocation, surgical therapy strategies become necessary. Above all mentally
      retarded or patients with neuromuscular disorders may necessitate surgical
      treatment. The two surgical main procedures are: 1. Removal of mechanical
      obstacles by reduction of the eminentia. 2. Creation of a mechanical obstacle
      towards the anterior condylar translation. The here presented case shows the
      treatment of a reccurent, fixed anterior TMJ-dislocation using a miniplate which
      enables a absolut heightening of the articular tubercle in a 76 years old lady
      with Morbus Alzheimer and Parkinson. Due to the high incidence of plate
      fractures, this well discribed therapy, known as miniplate eminoplasty, can not
      be considered as the treatment of choice for mandibular dislocation. It can be
      indicated in non-compliant patients or in patients with neuromuscular disorders
      or in the combination of both as in our case.

PMID- 17557645
TI  - Corporal oscillation during static biped posture in children with cerebral palsy.
AB  - This previous study was performed to compare the antero-posterior and medium
      lateral displacements and the speed of displacement of the COP of healthy
      children and compare them to children with cerebral palsy type spastic diparesy.
      This study had the participation of 10 healthy children (6 girls and 4 boys),
      between 5 and 10 (7,6 +/- 2,1) years old, and other 10 children, all diagnosed as
      CP type spastic diparesy, (5 girls and 5 boys), between 5 e 10 (7,3 +/- 1,8)
      years old. To collect the data, we used the antero-posterior (AP) e medium
      lateral (ML) displacements of the COP The parameters were compared by the
      variance analysis (ANOVA), and the post hoc test was Tukey's HSD. The level of
      significance adopted was p < 0,05. After the collect of data and statistical
      analysis, it was observed that the medium amplitude of the AP and ML
      displacements was higher in CP children, related to the healthy children: AP
      F(I,18)= 1,66 (p = 0,002), ML-F1,18)= 3,36 (p = 0,002). As the amplitude, the
      speed of the displacements was also different among the children. The speed of
      the displacements, AP and ML was higher in CP children - F(1,36) = 0,009 (p =
      0,00). There were no differences between the speed of AP and ML displacements,
      neither in the healthy children, nor in CP ones - F(1,36)= 0,00 (p = 0,87). The
      sensorial deficit found in CP children is an important issue in the increase of
      the amplitude and speed of displacement of the COP.

PMID- 17557646
TI  - Therapeutic ultrasound in the treatment of ankle plantarflexor spasticity in a
      unilateral stroke population: a randomized, single-blind, placebo-controlled
      trial.
AB  - Spasticity is a common and disabling symptom associated with Upper Motor Neuron
      Syndrome. The current methods of treatment for muscle spasticity have been
      claimed as unsatisfactory. Therapeutic ultrasound (US) is a common therapeutic
      modality in physiotherapy used for treating a wide variety of disorders. The aim
      of present study was to quantify the effects of continuous US on ankle
      plantarflexor spasticity in a randomized, single-blind, placebo-controlled trial.
      Twelve stroke patients (6 women and 6 men) randomly allocated to ultrasound (n =
      6) or placebo (n = 6) groups. The patients were treated with either US or sham US
      for three days per week, every other day for 15 treatment sessions. The primary
      efficacy measures were the H-reflex and the Ashworth Scale (AS). In experimental
      group there was a significant reduction in the Hmax/Mmax ratio (p = 0.03). The
      Hmax/Mmax ratio was increased in the placebo group patients (p > 0.05). The
      difference between two groups was statistically significant (p = 0. 02). In both
      groups there was a reduction in the posttreatment AS scores. The Ashworth scores
      demonstrated statistically significant changes in the US group (p = 0.04). There
      was no statistical difference, however, when these two groups were compared (p >
      0.05). Results from the present study show that treatment with US can reduce
      HmaxlMmax ratio as a measure of alpha motoneuron excitability and spasticity
      measure of AS in stroke patients with ankle plantarflexor spasticity.

PMID- 17557647
TI  - N-hexane neuropathy in screen printers.
AB  - BACKGROUND: To study the clinical and electrophysiological profile of n-hexane
      neuropathy in a tertiary care center of India. METHODS: Twenty five screen
      printers from five different factories, with peripheral neuropathy were included
      in the study. A detailed general physical, systemic and neurological examination
      was conducted Visual acuity, color vision and field charting was done in all the
      subjects. All patients were subjected to Folstein mini mental scale examination.
      Electrophysiological evaluation included motor and sensory conduction studies of
      the conventionally studied nerves of upper and lower limbs, Needle EMG of various
      distal and proximal muscles and patterned visual evoked responses. The
      electrophysiological profile was repeated every three months till one year. Sural
      nerve biopsy was studied in six patients. The patients were followed for a
      maximum of 4 years. RESULTS: Twenty three [92%] patients had sensory- motor
      neuropathy, while pure sensory neuropathy was seen in two. The sensory
      conductions were affected almost equally in upper as well as the lower limbs,
      while the motor conductions were affected more in the lower limbs than the upper
      limbs. The sensory conductions were not recordable in both the upper and the
      lower limbs in 18 [72%] patients. Motor conduction studies revealed an asymmetric
      and patchy involvement. Proximal conduction block was seen in 3 patients [12%].
      On needle EMG features of denervation were seen in all patients. P100 latency was
      normal in all. Sural nerve biopsy showed a selective decrease in large myelinated
      axons with demyelination. Axonal swelling with focal areas of demyelination was
      observed in two patients. CONCLUSIONS: The electrophysiological patterns as well
      as the histopathology reflect the pathophysiology of n-hexane neuropathy.

PMID- 17557648
TI  - Effect of skin temperature on RMS amplitude of electromyogram and mechanomyogram
      during voluntary isometric contraction.
AB  - The aim of this study is mainly to elucidate the relation between the
      modification of skin temperature and MMG signal properties depending on the
      contractile force. Ten healthy male volunteers, aged 22.8 +/- 0.7 (mean+/-SE)
      years, participated in this study. EMG and MMG signals were recorded during
      voluntary isometric contraction (20, 40, 60, and 80% MVC) of biceps brachii
      muscle under a skin temperature of 34 degrees C (control), 28 degrees C
      (cooling), and 40 degrees C (heating), respectively. A significant difference of
      MVC during elbow flexion was not recognized among the thermal conditions. Root
      mean square values of EMG and MMG (i.e., rms-EMG and rms-MMG) increased depending
      on the contractile level (P< 0.01). In the heating condition, the rms-MMG
      progressively increased in response to an increase of up to 60% MVC, however, it
      was nearly unchanged at a contractile force higher than 60% MVC The rms-EMG was
      not significantly influenced by the skin temperature. The rms-MMG significantly
      increased depending on the skin temperature at each contractile level (P< 0.01).
      There were significant interactions between contractile force and skin
      temperature for rms-MMG (P< 0.01). In conclusion, by modification of passive
      muscle temperature, rms-MMG was significantly altered in comparison with MVC and
      rms-EMG, which might be reflective of the changes of the mechanical contractile
      properties of muscle fibers.

PMID- 17557649
TI  - Inter-individual variability among the mechanomyographic and electromyographic
      amplitude and mean power frequency responses during isometric ramp muscle
      actions.
AB  - The purpose of this study was to examine the inter-individual variability in the
      patterns of responses for mechanomyographic (MMG) and electromyographic (EMG)
      amplitude and mean power frequency (MPF) of the vastus lateralis (VL) and
      rectusfemoris (RF) muscles during isometric ramp muscle actions of the leg
      extensors. Fifteen participants (mean +/- SD age = 24 +/- 4 years) performed two
      or three 6-s isometric ramp muscle actions with linear increases in torque from
      15% to 90% of the highest maximal voluntary contraction (MVC) torque. Surface MMG
      and EMG signals were simultaneously recorded from the VL and RF muscles. The
      composite (averaged across subjects) and individual patterns of responses for the
      normalized MMG and EMG amplitude and MPF vs. isometric torque relationships were
      analyzed. The composite patterns for MMG amplitude for the VL and RF muscles were
      fit with cubic models, although, only 87% of the individual patterns (13 of 15
      subjects) exhibited the same cubic pattern as the composite. For MMG MPF, the
      composite relationships were also cubic, but only 27% (4 subjects) and 40% (6
      subjects) of the individuals exhibited the same patterns for the VL and RF
      respectively. 60% (8 subjects) of the individual EMG amplitude patterns of
      responses matched the same curvilinear composite patterns for the VL and RE,
      while only 7% (1 subject) and 27% (4 subjects) of the EMG MPF responses were
      similar to the composite models for the VL and RF muscles, respectively.
      Therefore, since the individual patterns did not always match the composite
      relationships (i.e., inter-individual variability), these findings suggested that
      the MMG and EMG amplitude and MPF vs. isometric torque relationships should be
      examined on a subject-by-subject and muscle-by-muscle basis during isometric ramp
      muscle actions.

PMID- 17557650
TI  - Facioscapulohumeral muscular dystrophy. A quantitative electromyographic study.
AB  - BACKGROUND: Quantitative electromyography (EMG) using different needle techniques
      has not been performed or reported on a relatively large group of patients with
      facioscapulohumeral muscular dystrophy (FSHD). PURPOSE: To establish
      statistically: (1) correlations between clinical features of patients (age,
      disease duration and degree of weakness) and quantitative needle EMG/SFEMG,; (2)
      correlations between different EMG parameters in the patient group, and (3)
      quantitative EMG differences comparing patients with a healthy control group.
      METHODS: Nerve conduction studies, and needle EMG (motorunit analysis, MacroEMG,
      SFEMG) were performed on Mm. triceps brachii and Mm. tibialis anterior according
      to standard techniques on 20 patients with FSHD. RESULTS: Nerve conduction
      studies were normal. In Mm. triceps brachii and, to a lesser extent, Mm. tibialis
      anterior motorunit analysis and MacroEMG showed myopathic changes, that
      correlated with patient clinical parameters. In Mm. triceps brachii (but not in
      Mm. tibialis anterior) EMG results were statistically different in patients
      compared to control group data. The most sensitive indicators of a myopathy were
      MUP duration (motorunit analysis) and MUP area (MacroEMG). In the Mm. triceps
      brachii SFEMG revealed correlations between worsening pooled MCD data and patient
      clinical parameters. Pooled MCD results did not correlate with other MUP
      parameters. SFEMG showed abnormal jitter only in 2 patients with the longest
      disease duration. CONCLUSION: Quantitative EMG results are compatible with a
      mild, slowly progressive myopathy. The most sensitive indicators of early muscle
      disease were MUP duration (motorunit analysis) and MUP area (MacroEMG) that would
      not be detected on "routine" EMG SFEMG showed subtle, progressive worsening of
      neuromuscular junction physiology. However, quantitative EMG and SFEMG showed
      that muscle fiber degeneration and loss followed a course independent of muscle
      fiber regeneration and reinnervation.

PMID- 17557651
TI  - Study of the ulnar nerve compromise at the wrist of patients with carpal tunnel
      syndrome.
AB  - INTRODUCTION: That the ulnar nerve compromise occurs concomitant with the carpal
      tunnel syndrome (CTS) has been cited by previous studies. It seems that the
      previously mentioned incidence is much higher than what we observe in our
      electrodiagnosis studies. MATERIAL AND METHOD: A prospective study was designed
      to evaluate the incidence of ulnar nerve compromise in patients with
      electrodiagnostic evidence of CTS according to age and sex, and also to determine
      the site of ulnar nerve involvement. RESULTS: One hundred and sixty five limbs
      with standard elestrodiagnostic criteria of CTS were evaluated In 9.7% of the
      tested limbs, the ulnar nerve was involved. The site of the involvement was the
      wrist area in 43.75%. The elbow region was involved in 43.75%, and in 12.5%, the
      forearm region was involved. The most prevalent age range of concomitant
      involvement was 45-54 years old. In patents who had sensory symptoms in the 4th
      and 5th fingers, the incidence of concomitant ulnar nerve compromise was
      significantly higher (p < 0.001) than the patients without these symptoms.
      DISCUSSION: In patients with CTS, concomitant ulnar nerve compromise is much
      lower than the incidence mentioned in previous researches. Apparently the rate of
      involvement in wrist and elbow are equal. It is recommended that in evaluation of
      patients for CTS especially when the patient has sensory symptoms in the hand,
      special attention is paid to ulnar nerve involvement and two nerve comparison
      tests are interpreted with caution.

PMID- 17557652
TI  - A preliminary study into the criterion validity of the Modified Modified Ashworth
      Scale using the new measure of the alpha motoneuron excitability in spastic
      hemiplegia.
AB  - The Modified Ashworth Scale (MAS) is the most widely used clinical test for the
      measurement of muscle spasticity. This scale that suffers from limitations and
      lack of reliability and validity has recently been remodified. The aim of the
      present study is to investigate the criterion validity of the new Modified
      MAS(MMAS) in the upper limb in post-stroke hemiplegia, using the Hslope/Mslope
      (Hslp/Mslp) as a novel index of alpha motor neuron excitability. Prior to the
      validity study, the reliability of the MMAS was evaluated in 30 hemiplegic
      patients. The raters agreed on 23 patients (0. 76%). The MMAS had good inter
      rater reliability (K= 0.63, SE = 0.11, p < 0.001) for the assessment of wrist
      flexors spasticity in hemiplegic patients. 12 adult patients (7 women and 5 men)
      with first ever stroke resulting in hemiplegia with a mean age of 58.9 +/- 11.9
      years (range, 37-73) were included in the validity study. The outcome measures
      were the MMAS for the clinical assessment of spasticity, and the HslopelMslope
      and the Hmax/Mmax ratio for the electrophysiological evaluation. The results
      showed an increase in mean rank of Hslp / Mslp in patients with a score of 1, 2
      or 3 on the MMAS. However, the difference among the groups was not significant (p
      > 0.05). There was also no relationship between the clinical scale of MMAS and
      either the traditional [Hmax / Mmax ratio (r = -0.06)] or the new index [Hslp /
      Mslp (r = 0.24)] of spinal excitability. This preliminary study recruited a small
      number of patients, and failed to confirm a linear correlation between these
      variables. A study with a large number of patients is suggested to clarify the
      outcome.

PMID- 17557653
TI  - Common sense.

PMID- 17557654
TI  - A modest physician and his outrageous theory.

PMID- 17557655
TI  - Heroin in the corrections system: introduction.

PMID- 17557656
TI  - The Rhode Island Family Court's therapeutic response to parental substance abuse.

PMID- 17557657
TI  - An integrated program of buprenorphine in the primary care setting for HIV(+)
      persons in Rhode Island.

PMID- 17557658
TI  - An overview of heroin overdose prevention in the northeast: new opportunities.

PMID- 17557659
TI  - Drug court as an alternative to incarceration.

PMID- 17557660
TI  - Opioid addiction and incarceration: an overview.

PMID- 17557661
TI  - The use of palliative and hospice care in the nursing home setting.

PMID- 17557662
TI  - Drug intoxication deaths involving methadone, 2004-2005.

PMID- 17557663
TI  - The morbid influence of the prefix.

PMID- 17557664
TI  - [Anejaculation caused by haemosiderosis: male infertility in hereditary
      haemochromatosis].
AB  - A couple was investigated for subfertility. Haemochromatosis was suspected when
      the 36-year-old man had failure of ejaculation, fatigue and limited facial hair
      growth. Haemochromatosis was confirmed by an iron saturation of 102% (normal
      range: 20-45), a highly elevated serum ferritin concentration of 5468 mg/1l
      (normal range: 18-280) and highly elevated liver enzymes. Molecular genetics
      showed homozygous C282Y mutation of the HFE gene. Due to consequent venesection
      therapy, levels of ferritin and transferrin decreased and liver enzymes
      normalized. However luteinizing hormone and follicle stimulating hormone failed
      to increase to normal levels. Treatment with gonadotropins was then applied,
      which corrected ejaculation and semen characteristics. His partner failed to
      become pregnant with ovulation stimulation and intrauterine inseminations. After
      two unsuccessful IVF procedures she became pregnant in the third procedure.
      Haemochromatosis should be considered and iron studies performed if subfertility
      due to an endocrine disorder is being investigated. Deposition in the pituitary
      or the gonads of the HFE-mutated patients leads to hypogonadism. Most of the
      patients with C282Y mutation are homozygous (85-90%), but the majority of the
      carriers will not develop the disease. Deficiency of hepcidin, an important
      regulator for the iron metabolism, was suspected in our patient, based on the
      early onset of his disease and the low serum levels of hepcidin. The age at
      diagnosis and the start of venesections is critical for reversal of organ damage.
      Aggressive venesection can restore hypothalamic-pituitary-gonadal function,
      preventing further organ damage. But with increasing disease progression
      venesection will not restore azoospermia or the failure to ejaculate.

PMID- 17557665
TI  - [Surgical treatment of serious obesity: many questions on medical indications and
      results remain].
AB  - Obesity is associated with increased mortality and a whole spectrum ofco
      morbidities. Weight loss is indicated to relieve or prevent these co-morbidities
      and to reduce psychosocial and socio-economic consequences. The step-wise
      approach of obesity treatment is first the combination of energy restriction,
      physical activity and behavioural changes, followed by pharmacotherapy. The last
      step is bariatric surgery. From the results oflaparoscopic gastric banding, as
      published in this issue of the journal, two important aspects emerge. First, a
      change in the operation technique considerably reduced the long-term complication
      rate and second, the attrition rate decreased due to follow-ups managed by nurse
      practitioners. The study can also be criticised for not giving details of the
      selection procedures and the number of and reasons for rejection as well as for
      not reporting the improvements in co-morbidity and quality of life.

PMID- 17557666
TI  - [Effect of gastric banding on pharmacotherapy: not much known].
AB  - Following placement of gastric banding, the time that medication remains in the
      proximal part of the stomach may increase variably. This can lead to problems
      with oral administration of enteric coated or controlled-release preparations.
      Problems can be avoided by changing over to another form ofa dministration or
      sometimes by changing to another active compound. The placement of a gastric band
      changes the size of the stomach opening and the volume of the functional part of
      the stomach. Other than oral tablets, alternative formulations of medication,
      such as liquid or rectal forms are not always available, sometimes the only
      solution for giving some medication is to ground the tablet finely into powder
      for oral administration. For tablets with enteric coating or controlled release
      changing to normal tablets is not always perceivable. Patients should receive
      adequate instructions for intake and information on their therapy so that they do
      not fail to comply with treatment if tablets have a nasty taste after being
      ground into powder. The fat and water balance of both obese patients and patients
      who are losing weight is not usually known. Patients who have gastric banding
      should have medication dosages especially for medication with a narrow
      therapeutic index followed under strict supervision and have regular blood tests
      so that any necessary dosage adjustments can be made. At present little data are
      available to provide a comprehensive overview of the effects of gastric banding
      on pharmacotherapy. The potential consequences ofgastric banding on
      pharmacotherapy, together with the increasing frequency of gastric banding
      surgery, emphasize the need for further research in this field.

PMID- 17557667
TI  - [Gastric reduction in morbidly obese adults in the Netherlands].
AB  - Obesity results in several health problems, the most important of these being
      diabetes mellitus type 2. In patients with morbid obesity (BMI > or = 35 kg/m(2)
      and comorbidity or BMI > or = 40 kg/m(2)) in particular, prevention or treatment
      of health problems resulting from the obesity is only possible with considerable
      and lasting weight loss. Gastric reduction surgery with the adjustable gastric
      band has been shown to be safe and effective. This is also true for the more
      invasive techniques such as the gastric bypass and the biliopancreatic diversion.
      Surgical treatment is the only treatment that can induce substantial and lasting
      weight loss (> 50% of the excess weight, on average) in this patient group in the
      long run. Although the availability of surgical treatment is as yet inadequate in
      the Netherlands, it has recently improved considerably. Reimbursement of the
      treatment is however still an obscure issue and the reimbursement of the follow
      up is uncertain. Possibly, the current experiments with independent treatment
      centers will be able to put an end to this uncertainty.

PMID- 17557668
TI  - [Hereditary haemochromatosis: novel genes, novel diseases and hepcidin].
AB  - Since the discovery of the HFE gene of hereditary haemochromatosis in 1996
      several new genetic defects have been identified, enabling explanation of the
      cause and variety of this disease. To date, at least 5 major types of hereditary
      haemochromatosis have been recognised. All these genes encode for proteins that
      are involved in metabolic pathways relevant to hepcidin synthesis in the liver.
      Hepcidin is a small protein that regulates the activity of the iron exporting
      protein ferroportin in the basolateral membrane of duodenal cells and the cell
      membrane of macrophages and thereby controls serum iron concentration. Plasma
      hepcidin concentration is elevated in body iron excess and by inflammatory
      stimuli, and is lowered in erythroid iron demand, hypoxia and most types of
      hereditary haemochromatosis. It is the clinician's task to diagnose hereditary
      haemochromatosis before irreversible tissue damage arises and at the same time to
      differentiate between ongoing iron accumulation and increasingly prevalent
      disorders with elevated serum ferritin such as the metabolic syndrome.

PMID- 17557669
TI  - [Diagnostic image (324). A man with a necrotic finger].
AB  - A 35-year-old man presented with progressive infected necrosis of the second
      digit of his right hand, caused by exposure to hydrogenfluoride.

PMID- 17557670
TI  - [Sustained weight loss 2 years after laparoscopic adjustable gastric banding for
      morbid obesity].
AB  - OBJECTIVE: To analyse the results of the laparoscopic adjustable gastric banding
      (LAGB) procedure for morbid obesity. DESIGN. Retrospective, descriptive. METHOD:
      From November 1, 1995 to May 31, 2005, laparoscopic adjustable banding surgery
      was performed in St. Antonius Hospital, Nieuwegein, the Netherlands, in 411
      patients. Inclusion criteria were BMI > or = 40 kg/ m(2) or BMI > 35 kg/m(2) and
      severe comorbidity with > 3 attempts at weight loss in the past. Selection,
      inclusion and follow-up were performed in a specialised, multidisciplinary
      setting. Height, weight, and complications were prospectively recorded. In 1995
      2000 the perigastric surgical procedure was used and in 2000-2005 the pars
      flaccida method. RESULTS: The study group consisted of 350 (85%) women and 61
      (I5%) men with a median age of 38 years (range 17-60). Out of these 411 patients,
      the median weight was 133.4 kg, the median overweight, 69.6 kg and the median BMI
      46.3 kg/m2. Two years after surgery, data was known for 267 patients where 206
      (77%) had a weight loss > 30%, and 7 patients (3%) a weight gain. The median BMI
      difference was then -10.2 kg/m2 (range +4.7--26.4). The median loss of overweight
      was 46.3% (+10.00--97.8). The weight loss remained stable in the following years.
      The most commonly seen complications were fundus slippage (13%) and port-a-cath
      related complications (7%). These occurred more often in patients who had had the
      perigastric method surgery than in the parsflaccida surgical method. CONCLUSION:
      Three quarters of the patients with morbid obesity who received laparoscopic
      gastric banding surgery had achieved and sustained weight loss at 2 years
      following surgery. The pars-flaccida method resulted in fewer complications than
      the perigastric surgical method.

PMID- 17557671
TI  - [Reconstruction of a cheek defect in three patients].
AB  - A woman aged 62 and two men aged 52 and 26 all with a cheek defect following
      resection of a recurrence of a lentigo maligna, a recurrence of a basal-cell
      carcinoma of the wispy type and a dermatofibrosarcoma protuberans respectively,
      all underwent cheek reconstruction. The rotation flap technique was used in the
      first two patients. The third patient was treated with a cervicofacial
      musculocutaneous transposition flap and underwent postoperative radiotherapy due
      to the high risk of recurrence. All 3 patients made a good recovery. Defects
      after radical resection of malignant head and neck skin tumours can be treated by
      several reconstruction techniques depending on the site, size, and shape of the
      defect. A local transposition flap is the preferred method of reconstruction. It
      is important to respect the aesthetic units of the face in order to achieve the
      best aesthetic and functional results.

PMID- 17557672
TI  - [Adverse effects of the tyrosine-kinase inhibitor sunitinib, a new drug for the
      treatment of advanced renal-cell cancer].
AB  - Three patients with advanced renal-cell cancer were treated with sunitinib 50 mg
      daily for 4 weeks followed by a rest period of 2 weeks because of progressive
      disease. The first patient developed stomatitis and a painful blister on his
      foot. Complaints disappeared after temporary discontinuation of treatment. Re
      treatment at a lower dosage was successful until disease progression. The second
      patient developed skin discolouration, fatigue, fever and diarrhoea. After
      treatment was interrupted shortly, these symptoms disappeared and sunitinib was
      recommenced at a lower dosage. The patient went on to develop stomatitis,
      thrombocytopenia and hypertension (treated with amlodipine). She subsequently had
      hand-foot syndrome. She died due to brain metastases. In the third patient
      symptoms of disease returned during the rest period, because of which he received
      a reduced dosage of sunitinib on a continuous base. He developed diarrhoea which
      disappeared after a short interruption of the drug. Sunitinib has been approved
      for the treatment of advanced renal-cell cancer and imatinib-resistant gastro
      intestinal stromal tumours. This novel targeting molecule is a tyrosine-kinase
      inhibitor of vascular endothelial growth-factor receptors, platelet-derived
      growth-factor receptors and c-Kit. It can induce adverse events that differ from
      those observed in treatment with conventional cytotoxic agents. The adverse
      effects are reduced by lowering the dosage and in the rest period within the
      treatment cycle.

PMID- 17557673
TI  - [Three previously healthy persons with a stress fracture].

PMID- 17557674
TI  - [Iron-deficiency anaemia: a sign that requires an adequate explanation].

PMID- 17557675
TI  - Addressing global health research in the national interest.

PMID- 17557676
TI  - Maternal self-report of oral health in 4-year-old Pacific children from South
      Auckland, New Zealand: findings from the Pacific Islands Families Study.
AB  - OBJECTIVES: To report on the oral health risk in a disadvantaged group of 4-year
      old Pacific children and their mothers living in South Auckland, New Zealand.
      METHODS: The Pacific Islands Families study follows a cohort of Pacific infants
      born in 2000. Maternal self-report of mother and child's oral health practices
      and child's filling and extraction experience was undertaken at interview
      approximately 4 years postpartum. RESULTS: Overall, 1,048 mothers of children
      were interviewed. Children's reported oral health practices were generally poor,
      with 47 percent brushing < or =1/day, 47 percent having no adult assistance with
      brushing, 57 percent routinely snacking or drinking immediately prior to bed, and
      26 percent yet to receive their first dental checkup. Maternal practices were
      also poor, with 34 percent brushing < or =1/day and 50 percent having never seen
      or last visiting a dentist over 5 years ago. Significant differences were seen in
      many practices between the major ethnic subgroups. Of children attending the
      school dental service, 22 percent were reported having at least one filling
      and/or extraction. In multivariable analyses, variables corresponding to mother's
      toothbrushing frequency, child snacking or drinking prior to bed, and duration of
      breastfeeding were significantly associated with reported filling and/or
      extraction experience; but no difference was seen between the three major
      maternal ethnic subgroups. CONCLUSIONS: Many mothers and their Pacific children
      have poor basic oral hygiene and dietary practices that increase the oral health
      risk in these children. Culturally appropriate and targeted strategies aimed at
      these modifiable practices need to be widely promoted so that the oral health
      burden carried by Pacific children can be reduced.

PMID- 17557677
TI  - A review of a community program aimed at preventing early childhood caries among
      Jerusalem infants--a brief communication.
AB  - Early childhood caries (ECC) has not been adequately investigated in Israel. A
      previous Jerusalem study has demonstrated a potential effect on toothbrushing
      among infants. The present study was initiated in order to examine caries
      prevalence and the potential effect of a community intervention program.
      OBJECTIVES: This study aims to review an intervention program and assess ECC
      distribution and associated variables. METHODS: The study sample included 1,500
      infants in matched "intervention" and "control" Mother and Child Health centers.
      The 2-year program, initially including all children at the age of 6 months,
      focused on the free distribution of toothbrushes and toothpastes. ECC prevalence
      was determined in a cross-sectional study. RESULTS: At 2.5 years, 596 children
      were examined (40 percent compliance). About half of the parents reported that
      they had participated once or not at all over the 2-year period, which
      demonstrated low program participation. Among the examined children, ECC
      prevalence was 15.3 percent. No difference in caries levels was found between the
      program and control groups. The reported level of brushing twice daily was 13.9
      percent, while 26.8 percent reported not brushing at all. Eighty-one percent
      reported going to bed at night with a bottle. Children who drank sugar-sweetened
      beverages had ECC levels significantly higher than those who drank milk or
      natural juice (18.8 percent versus 8.9 percent). CONCLUSIONS: The dental health
      and behavior and lack of intervention success emphasized the need to seek a more
      effective strategy. Emphasis on toothbrushing might not be the only nor optimal
      solution for this serious public health problem.

PMID- 17557678
TI  - Concurrent tobacco use in a random sample of UK-resident Bangladeshi men.
AB  - The literature on concurrent tobacco (CCT) use, i.e., regularly using both smoked
      and chewed tobacco, is sparse. OBJECTIVES: This study aims to establish the point
      prevalence of CCT use in a randomly selected sample of UK-resident Bangladeshi
      males, compare CCT users with other tobacco users (smokers alone and chewers
      alone), and model the factors for CCT use and chewing tobacco use alone. METHODS:
      A cross-sectional bilingual interview survey collecting data on age, marital
      status, social class, employment status, home ownership and overcrowding, self
      assessed health and chronic illness episodes, social capital, nicotine
      dependence, and oral pain was used. Carbon monoxide readings validated smoked
      tobacco use. Logistic regressions were used for data analysis. RESULTS: The
      initial response rate was 59 percent. Sample mean age was 40.7 years. CCT
      prevalence was estimated at 22 percent, practiced by older respondents of limited
      educational status. CCT users more likely had only average or poor self-rated
      health and more likely reported current oral pain compared with tobacco smokers.
      A wife chewing tobacco distinguished CCT users, as compared with tobacco smokers
      alone. CONCLUSIONS: In this sample of adult Bangladeshi males, CCT use was
      prevalent. CCT users more likely had a partner who was also a tobacco chewer, as
      compared with tobacco smokers.

PMID- 17557679
TI  - Oral cancer prevention and early detection knowledge and practices of Illinois
      dentists--a brief communication.
AB  - OBJECTIVES: The purpose of the study was to assess Illinois dentists' self
      reported knowledge and practices concerning oral cancer prevention, early
      detection, and management as a baseline prior to conducting interventions
      designed to increase dentists' capacity to detect and manage oral cancers and
      counsel their patients about risk reduction. METHODS: A weighted sample to
      represent licensed dentists in 19 counties yielded 518 dentists who responded to
      a 38-item mailed survey in 2004. RESULTS: Over 92 percent of the dentists
      reported providing oral cancer exams. However, many are not doing them properly
      or at frequent intervals. Over two-thirds had oral cancer continuing education,
      but 40 percent had it more than 2 years prior to the survey. Training in risk
      counseling was rare. CONCLUSIONS: Interventions are needed to assure appropriate
      skill and knowledge levels for oral cancer early detection, management, and risk
      counseling by Illinois dentists.

PMID- 17557680
TI  - Development of a word recognition instrument to test health literacy in
      dentistry: the REALD-30--a brief communication.
AB  - OBJECTIVE: This study aims to develop and pilot test a dental word recognition
      instrument. METHODS: The development of our instrument was based on the Rapid
      Estimate of Adult Literacy in Medicine (REALM), an efficient word recognition
      instrument used to assess health literacy in the medical arena. Our instrument,
      Rapid Estimate of Adult Literacy in Dentistry (REALD-30), consisted of 30 common
      dental words with various degrees of difficulty. It was administered to 202
      English-speaking adults recruited from outpatient medical clinics. We examined
      the instrument's internal reliability using Cronbach's alpha and its validity by
      correlating the REALD-30 score to two dental outcomes (perceived dental health
      status and oral health-related quality of life) and medical health literacy.
      RESULTS: REALD-30 scores were significantly correlated with REALM scores. REALD
      30 was significantly related to perceived dental health status in the bivariate
      analysis. It also was significantly related to oral health-related quality of
      life in a multivariate analysis. In contrast, medical health literacy was not
      related to either of the dental outcome measures. CONCLUSIONS: The new REALD-30
      instrument displays good reliability but only partial validity. Results suggest
      that dental health literacy may be distinct from medical health literacy and may
      have an independent effect on dental health outcomes.

PMID- 17557681
TI  - Evaluation of a word recognition instrument to test health literacy in dentistry:
      the REALD-99.
AB  - OBJECTIVE: This study aims to evaluate a dental health literacy word recognition
      instrument. METHODS: Based on a reading recognition test used in medicine, the
      Rapid Estimate of Adult Literacy in Medicine (REALM), we developed the Rapid
      Estimate of Adult Literacy in Dentistry (REALD-99). Parents of pediatric dental
      patients were recruited from local dental clinics and asked to read aloud words
      in both REALM and REALD-99. REALD-99 scores had a possible range of 0 (low
      literacy) to 99 (high literacy); REALM scores ranged from 0 to 66. Outcome
      measures included parents' perceived oral health for themselves and of their
      children, and oral health-related quality of life of the parent as measured by
      the short-form Oral Health Impact Profile (OHIP-14). To determine the validity,
      we tested bivariate correlations between REALM and REALD-99, REALM and perceived
      dental outcomes, and REALD-99 and perceived dental outcomes. We used ordinary
      least squares regression and logit models to further examine the relationship
      between REALD-99 and dental outcomes. We determined internal reliability using
      Cronbach's alpha. RESULTS: One hundred two parents of children were interviewed.
      The average REALD-99 and REALM-66 scores were high (84 and 62, respectively).
      REALD-99 was positively correlated with REALM (PCC = 0.80). REALM was not related
      to dental outcomes. REALD-99 was associated with parents' OHIP-14 score in
      multivariate analysis. REALD-99 had good reliability (Cronbach's alpha = 0.86).
      CONCLUSIONS: REALD-99 has promise for measuring dental health literacy because it
      demonstrated good reliability and is quick and easy to administer. Additional
      studies are needed to examine the validity of REALD-99 using objective clinical
      oral health measures and more proximal outcomes such as behavior and compliance
      to specific health instructions.

PMID- 17557682
TI  - Development and testing of the Test of Functional Health Literacy in Dentistry
      (TOFHLiD).
AB  - OBJECTIVE: This study aims to evaluate the reliability and validity of the Test
      of Functional Health Literacy in Dentistry (TOFHLiD), a new instrument to measure
      functional oral health literacy. METHODS: TOFHLiD uses text passages and prompts
      related to fluoride use and access to care to assess reading comprehension and
      numerical ability. Parents of pediatric dental patients (n = 102) were
      administered TOFHLiD, a medical literacy comprehension test (TOFHLA), and two
      word recognition tests [Rapid Estimate of Adult Literacy in Dentistry (REALD),
      Rapid Estimate of Adult Literacy in Medicine (REALM)]. This design provided
      assessments of dental and medical health literacy by all subjects, both measured
      with two different methods (reading/numeracy ability and word recognition).
      Construct validity of TOFHLiD was assessed by entering the correlation
      coefficients for all pairwise comparisons of literacy instruments into a
      multitrait-multimethod matrix. Internal reliability of TOFHLiD was assessed with
      Cronbach's alpha. Criterion-related predictive validity was tested by
      associations between the TOFHLiD scores and the three measures of oral health in
      multivariate regression analyses. RESULTS: The correlation coefficient for
      TOFHLiD and REALD-99 scores (monotrait-heteromethod) was high (r = 0.82, P <
      0.05). Coefficients between TOFHLiD and TOFHLA (heterotrait-monomethod: r = 0.52)
      and REALM (heterotrait-heteromethod: r = 0.53) were smaller than coefficients for
      convergent validity Cronbach's alpha for TOFHLiD was 0.63. TOFHLiD was positively
      correlated with OHIP-14 (P < 0.05), but not with parent or child oral health.
      TOFHLA was not related to dental outcomes. CONCLUSIONS: TOFHLiD demonstrates good
      convergent validity but only moderate ability to discriminate between dental and
      medical health literacy. Its predictive validity is only partially established,
      and internal consistency just meets the threshold for acceptability. Results
      provide solid support for more research, but not widespread use in clinical or
      public health practice.

PMID- 17557683
TI  - Analyzing location-based accessibility to dental services: an Ohio case study.
AB  - Oral health is important to overall health. Therefore, dental services should be
      available and accessible in order for patients to receive care. OBJECTIVE: This
      study aims to identify regional inequities in dental provider location and
      suggest an innovative methodology that could be useful in establishing new dental
      facilities that are geographically accessible. METHODS: Using a census of dentist
      locations for the state of Ohio in 1998, geographical accessibility to dental
      care was analyzed. A geographic information systems (GIS)-based model to evaluate
      the regional distribution of dentists was developed. In this article, it is
      applied to estimate the number of new dental facilities needed based on the
      geographical proximity or distance to nearest dentist or dental facility. Results
      are interactively displayed and mapped with GIS for visualization. RESULTS: Four
      hundred thirteen of 1,008 zip codes in Ohio did not have dentists. Using a
      service standard of S = 5 (all zip codes without dentists must be within 5 miles
      of a zip code with a dentist), 307 zip codes were not served by dentists. With a
      standard of S = 10, only 45 zip codes in Ohio were not served by dentists, with
      only 24 additional offices needed to be located to allow accessibility to a
      dentist within 10 miles. CONCLUSIONS: Using GIS and geographical techniques to
      reveal and solve the potential locational inequities in accessibility to dental
      care, this work links oral health policy with geographical techniques.

PMID- 17557684
TI  - Socioeconomic inequalities in child oral health: a comparison of discrete and
      composite area-based measures.
AB  - OBJECTIVES: This study aims to examine the relationship between child caries
      prevalence and six discrete area-based measures of socioeconomic status (SES).
      Comparisons were also made of the discrete SES measures and the Socio-Economic
      Index for Areas (SEIFA) composite index in explaining child caries experience.
      METHODS: Oral health data were electronically captured for 58,463 4- to 16-year
      old children enrolled in the School Dental Service of South Australia in 2001.
      Socioeconomic measures for the same year were extracted from Basic Community
      Profiles for postcodes available from the Australian Bureau of Statistics.
      RESULTS: There were generally consistent linear relationships between caries
      prevalence and SES with children having poorer oral health residing in areas of
      greater socioeconomic disadvantage. This was evident across all SES measures,
      although some variations were shown for some measures. Children from more
      socioeconomically disadvantaged areas had higher odds of having either one or
      more decayed, missing, or filled teeth or four or more decayed, missing, or
      filled teeth. Most discrete SES measures explained a significant amount of the
      variance in oral disease beyond that accounted for by the composite SEIFA index.
      CONCLUSIONS: Pervasive social inequality in child oral health exists in
      Australia. Specific area-based measures of SES are valuable in documenting these
      inequalities and may be more meaningful than composite area-based indices of SES.

PMID- 17557685
TI  - Follow-up of an exercise-based treatment for children with reading difficulties.
AB  - This study reports the results of a long-term follow-up of an exercise-based
      approach to dyslexia-related disorders (Reynolds, Nicolson, & Hambly, Dyslexia,
      2003; 9(1): 48-71). In the initial study, children at risk of dyslexia were
      identified in 3 years of a junior school. One half then undertook a 6 month, home
      based exercise programme. Evaluation after 6 months indicated that the exercise
      group improved significantly more than the controls on a range of cognitive and
      motor skills. Critics had suggested that the improvement might be attributable to
      artifactual issues including Hawthorne effects; an initial literacy imbalance
      between the groups; and inclusion of non-dyslexic participants. The present study
      evaluated the issue of whether the gains were maintained over the following 18
      months, and whether they were in some sense artifactual as postulated by critics
      of the original study. Comparison of (age-adjusted) initial and follow-up
      performance indicated significant gains in motor skill, speech/language fluency,
      phonology, and working memory. Both dyslexic and non-dyslexic low achieving
      children benefited. There was also a highly significant reduction in the
      incidence of symptoms of inattention. Interestingly there were no significant
      changes in speeded tests of reading and spelling, but there was a significant
      improvement in (age-adjusted) reading (NFER). It is concluded that the gains were
      indeed long-lasting, and that the alternative hypotheses based on potential
      artifacts were untenable, and that the exercise treatment therefore achieved its
      applied purpose. Further research is needed to determine the underlying reasons
      for the benefits. Possible (and potentially synergistic) explanations include:
      improved cerebellar function (neural level); improved learning ability and/or
      attentional ability (cognitive level); improved self-esteem and self-efficacy
      (affective level); and improved parental/familial support (social level).

PMID- 17557686
TI  - No evidence that an exercise-based treatment programme (DDAT) has specific
      benefits for children with reading difficulties.
AB  - Reynolds and Nicolson (Dyslexia: An International Journal of Research & Practice,
      2007) report follow-up data 12 and 18 months after a period of intervention
      consisting of an exercise-based treatment programme (Dyslexia Dyspraxia Attention
      Treatment Programme, DDAT). The findings suggested the treatment had effects on
      bead threading, balance, rapid naming, semantic fluency and working memory but
      not on reading or spelling. We argue that the design of the study is flawed, the
      statistics used to analyse the data are inappropriate, and reiterate other issues
      raised by ourselves and others in this journal in 2003. Current evidence provides
      no support for the claim that DDAT is effective in improving children's literacy
      skills.

PMID- 17557687
TI  - Deficient morphological processing in adults with developmental dyslexia: another
      barrier to efficient word recognition?
AB  - Research on dyslexia has focused on the phonological level of linguistic
      analysis. Here we extend the investigation of the linguistic competence of
      individuals with dyslexia to the morphological level of linguistic analysis. We
      examine whether adult Hebrew readers with dyslexia extract and represent
      morphemic units similarly to normal readers. Using the priming paradigm in the
      word fragment completion task, we measured the magnitude of morphological priming
      and contrasted this effect with the repetition priming effect. Students with
      normal reading ability showed the typical repetition priming effect. A comparable
      repetition priming effect was also found for the dyslexic group as a whole.
      However, when the dyslexics were classified into three subtypes according to
      their phonological and orthographic decoding skills, repetition priming effects
      were significant only for the phonological dyslexia subgroup but not for the
      surface or mixed dyslexia subgroups. Furthermore, students with normal reading
      ability showed strong morphological priming, comparable in strength to the
      repetition priming effect. In contrast, the dyslexic readers did not show
      morphological priming, neither the dyslexia group as a whole, nor any of the
      subgroups. Our results highlight an additional source for dyslexics' difficulties
      with word recognition which lie at the level of morphological processing.

PMID- 17557688
TI  - Computerized screening for visual stress in children with dyslexia.
AB  - Visual stress-a condition in which unpleasant visual symptoms are experienced
      when reading-has been reported to be more prevalent in dyslexic individuals but
      at the present time the relationship between dyslexia and visual stress remains
      controversial. ViSS, a computerized visual stress screener that incorporates
      reading-like visual search, has recently shown promise in studies with unselected
      samples of primary and secondary school children. This study investigated the use
      of ViSS with dyslexic children. Dyslexic children identified as having high
      visual stress showed significantly higher per cent increases in reading rate with
      a coloured overlay and reported significantly higher critical symptoms of visual
      stress, compared to dyslexic children with low visual stress. The same results
      were found for reading-age controls, indicating that ViSS can be equally
      effective with normal readers as well as with children with dyslexia. Compared to
      reading-age controls, dyslexic children were found to have significantly higher
      susceptibility to visual stress, significantly larger per cent increases in
      reading rate with an overlay, and significantly higher critical and non-critical
      symptoms of visual stress. Extrapolated to unselected population samples, the
      data also suggest that visual stress is more likely to be found in people with
      dyslexia than in people who do not have dyslexia. These results, which point to
      an important link between the two conditions, are discussed in relation to
      current theories that attribute visual stress to either a magnocellular
      dysfunction or cortical hyperexcitability.

PMID- 17557689
TI  - Beyond self-actualization.

PMID- 17557690
TI  - HIV/AIDS in Bangladesh: the role of government in health and human services
      administration.
AB  - Explore the susceptibility of the People of Bangladesh to HIV/AIDS. The
      prevalence of HIV/AIDS in the neighboring countries may have reasonable
      proportions of impact in our country. According to the data provided by a
      Bangladesh University, the number of detected People living with HIV/AIDS reached
      567 as of Dec 2005. Importance of appropriate education on safe sex, violence,
      HIV/AIDS at all levels of our society, including counseling and advocacy, is
      emphasized and recommends governmental policy and research for prevention of
      HIV/AIDS.

PMID- 17557691
TI  - Public health coalitions: patterns and perceptions in state immunization
      programs.
AB  - The central question of this research is whether state public health programs
      collaborate with other public and private institutions to promote public health
      goals. Public health administration is highly bureaucratized and dependent upon
      government support, but administrators can establish coalitions as adjunct to
      more traditional means of providing public health services. We explain how public
      health coalitions are beneficial to providing public health services and then
      assess whether administrators in state immunization programs collaborate with
      both the public and private sectors. The results of a 50-state survey of state
      immunization program officials suggest that coalitions between state immunization
      programs and institutions of the public and private sectors are common. Moreover,
      most state program officials think that the more extensive use of immunization
      coalitions is important for improving state immunization coverage. Our findings
      also indicate that some states have not yet maximized the potential involvement
      of the private sector to collaborate in public health efforts.

PMID- 17557692
TI  - Study of American and Chinese family members' evaluations on institutionalized
      care for their older parents: potential development in the future.
AB  - The evaluations on institutionalized care facilities from family members, after
      their loved ones moved into such services, are very different from culture to
      culture, family to family and person to person. According to a recent survey in
      the United States and China, it is found that different cultures and the
      different health conditions of the residents strongly influence family member's
      viewpoints on institutionalized care services. It is also found that the
      availability of the institutionalized care facilities plays a significant role,
      which strongly affects family members' evaluations on nursing home services.

PMID- 17557693
TI  - Integrating health and social services for older adults: a case study of
      interagency collaboration.
AB  - As public housing residents age in place, they require health and social services
      outside of those traditionally offered by housing authorities. A promising
      response to these emerging needs is for housing authorities to collaborate with
      local public health departments to deliver coordinated services to older adult
      residents. Aging residents' health needs include health promotion activities,
      preventive health services, health education, and mental health services, among
      others. From 2001-2004 the New York City Department of Health and Mental Hygiene
      (DOHMH) and the New York City Housing Authority (NYCHA) collaborated to implement
      the Senior Wellness Project. This outreach program integrated health and social
      services provided by DOHMH and NYCHA, and delivered these services to older adult
      residents on site in 21 New York City public housing developments. Services were
      rendered at senior centers located in the housing developments and in residents'
      apartments. The program also referred residents to community healthcare providers
      to address special needs such as addiction. This article retroactively applies a
      formal model for interagency collaboration, the Stages of Collaboration, to
      describe and analyze the process of collaboration between DOHMH and NYCHA. It
      identifies the successes and shortcomings of the collaborative process, and
      explores the theory that successful collaboration leads to inherent challenges
      for implementation. Recommendations are then made for other public housing and
      public health agencies that have considered collaborating to address the needs of
      public housing residents who are aging in place.

PMID- 17557694
TI  - Effect of local competition on the willingness of community pharmacies to supply
      medication therapy management services.
AB  - The Medicare Prescription Drug, Improvement, and Modernization Act of 2003 (MMA)
      provides a prescription drug benefit for Medicare-eligible seniors that includes
      access to medication therapy management services (MTMS) through pharmacists. We
      theorize that local community pharmacy market competition affects the decision of
      individual community pharmacies to provide MTMS. Our model suggests that MTMS
      services are more apt to be supplied in markets at the extremes of community
      pharmacy concentration (very low and very high). We found that local community
      pharmacy competition affected the service choices made by the pharmacy decision
      makers willing to provide MTMS in a manner consistent with our theory. As a
      result, patient access to MTMS services depends on both (1) patient access to
      pharmacies willing to provide MTMS and (2) the level of local community pharmacy
      competition.

PMID- 17557695
TI  - Racial and ethnic disparities in the financial burden of prescription drugs among
      older Americans.
AB  - This study examines racial and ethnic disparities in the financial burden of
      prescription drugs among older Americans using a market and an egalitarian model.
      A nationally representative data set, the Medical Expenditure Panel Survey 2002,
      was used. The financial burden of prescription drugs was measured by the out-of
      pocket expenditure and proportion. In the market model (utilization adjustment).,
      utilization was measured at the annual aggregate level by the total number of
      prescription drugs, the average refills and the average quantity per prescription
      drug. In the egalitarian model (need adjustment)., health was measured by 15
      chronic and costly diseases and the SF-12. Individuals 65 years or older were
      included. Nationally representative estimates were calculated. Raw racial and
      ethnic disparities were observed in the bivariate analyses between non-Hispanic
      whites and Hispanics in the out-of-pocket expenditure and proportion, and between
      non-Hispanic whites and non-Hispanic blacks in the out-of-pocket proportion.
      However, these disparities disappeared after controlling for utilization or
      health needs. Insurance status contributed the most to the disparities in the
      financial burden of prescription drugs. In conclusion, The disparities in the
      financial burden of prescription drugs between non-Hispanic elderly whites and
      Hispanics may be attributable to differences in utilization patterns. However,
      whether health disparities contribute to disparities in the financial burden of
      prescription drugs requires studies of specific diseases.

PMID- 17557696
TI  - The effect of insurance type on prescription drug use and expenditures among
      elderly Medicare beneficiaries.
AB  - The debate over the impact of the new Medicare prescription drug benefit (Part D)
      has intensified in anticipation of its implementation. This paper contributes
      additional information related to the effect of different types of prescription
      drug coverage plans on use and expenditures among elderly Medicare beneficiaries.
      Cross-sectional design using data from the 2002 Medical Expenditures Panel Survey
      (MEPS). The two dependent variables were (1) prescription drug use and (2)
      expenditures. The main independent variable was the type of drug insurance
      (Medicare FFS only [no Rx insurance], Medicare FFS + Rx insurance and Medicare
      HMO). Bivariate and multivariate analyses were used to test the effect of
      insurance type, and beneficiaries' characteristics, on likelihood and level of
      drug use, as well as expenditures. The findings showed that average total drug
      expenditures among Medicare FFS enrollees who had Rx insurance (non-HMO) were
      higher ($182.51) than that of Medicare FFS enrollees with no Rx insurance. In
      addition, the former group had a higher likelihood (any use) of using prescribed
      medications. On the other hand, no differences in the likelihood of use were
      detected between Medicare HMO and Medicare FFS (no Rx insurance) enrollees.
      However, Medicare HMO enrollees had a higher level of drug use. In conclusion,
      The differences in drug use and expenditures by insurance type imply that each
      party (Medicare, Medicare Advantage plans, employers) will have a different set
      of disincentives for involvement in Medicare Part D.

PMID- 17557697
TI  - Utilization of prescription medications and ancillary pharmacy services among
      rural elders in west Texas: distance barriers and implications for telepharmacy.
AB  - We examine the relationship between distance and access to prescription
      medications and ancillary pharmacy services among rural elders in west Texas.
      Further understanding this relationship is important because programs such as
      telepharmacy are largely justified on the basis of reducing distance barriers. We
      use data from the Texas Tech 5000 survey to evaluate the relationship between
      distance and access. In addition, we examine whether regulations that prohibit
      competition between independent pharmacies and telepharmacies create a distance
      barrier to prescription medication. Our findings suggest that distance is a
      barrier to access, but telepharmacy regulations in Texas do not exacerbate the
      impact of distance.

PMID- 17557698
TI  - Meaning in motivation: does your organization need an inner life?
AB  - Leaders of health care organizations are increasingly interested in ways to
      attract, retain, and gain commitment from their employees. This interest is
      created in part because high turnover rates and the lack of commitment negatively
      affect the provision of care and the bottom line in their organizations. In a
      quality and cost conscious health care environment, health care managers need to
      find solutions for these difficult issues; solutions that are effective,
      efficient and sustainable. What can be done? This article reviews, amplifies, and
      extends work that has been done in the area of "meaningfulness of work" in the
      context of employee retention and commitment. It begins with an exploration of
      the problems caused by lack of employee engagement and commitment including their
      impact on quality and costs. It then summarizes both the theoretical and applied
      research in the area of meaning and work. It also introduces the basic principles
      of Viktor Frankl's logotherapy (Frankl, 1998) as a foundation for encouraging the
      integration of meaning and work. The seminal work by Pattakos (2004) is used to
      demonstrate how Frankl's principles can be applied to healthcare work settings.
      Finally, the article provides suggestions for increasing employee commitment and
      engagement through identifying meaning and purpose in work.

PMID- 17557699
TI  - Colorado nursing history: guarding the health of thousands.

PMID- 17557700
TI  - Nursing workforce in Colorado.

PMID- 17557701
TI  - APN bill killed in committee, but APNs not defeated.

PMID- 17557702
TI  - Assuring patient safety: registered nurses' responsibility in all roles and
      settings to guard against working when fatigued.
AB  - Education: 6. Schools of nursing should address decision-making within their
      curriculum related to the impact that fatigue and the habitual The American
      Nurses Association (ANA) takes the position that, regardless of the number of
      hours worked, all registered nurses have an ethical responsibility to carefully
      consider their level of fatigue when deciding whether to accept any assignment
      extending beyond their regularly scheduled work day or week, including a
      mandatory or voluntary overtime assignment.

PMID- 17557703
TI  - Competitive bidding: an update.

PMID- 17557704
TI  - The doctorate in clinical laboratory science: a view of the process of
      integration into healthcare.

PMID- 17557705
TI  - Clinical laboratory sciences curriculum redevelopment: an application of change
      theories.
AB  - The Department of Clinical Laboratory Sciences at Rosalind Franklin University of
      Medicine and Science (RFUMS) experienced a steady decline in the number of
      applicants for the Clinical Laboratory Sciences (CLS) Program, even though the
      department regularly received inquiries from qualified students. The faculty
      recognized the undergraduate-degreed prospects' desires for both an advanced
      degree and the procurement of entry-level clinical laboratory knowledge and
      skills. To address this perceived need, the CLS department developed and
      implemented a new degree option, the entry-level master's. The new curriculum
      resulted from a transformational process incorporated into the normal
      developmental process of curriculum change. This article explores various change
      theories that were manifested during this transformation process, along with
      barriers to change and how to overcome them. In addition, the authors demonstrate
      the need for creation of this entry-level program and provide a curriculum
      outline.

PMID- 17557706
TI  - Advanced alcoholic cirrhosis: a case report.

PMID- 17557707
TI  - Biomarkers for inflammatory bowel disease.
AB  - Currently there is no single biomarker or panel of markers which is diagnostic of
      IBD generally, or CD and UC specifically. Diagnosis of IBD still requires
      radiographic, endoscopic, and microscopic examination. Since GI markers of
      inflammation are continuously being uncovered, and given that statistical power
      can be enhanced with multi-marker panels, we are hopeful that the medical
      laboratory will have the ability, in the near future, to support a non-invasive
      diagnosis of an inflammatory bowel disease.

PMID- 17557709
TI  - Evaluating distance learning in clinical laboratory science.
AB  - OBJECTIVE: The purpose of this study was to determine if there were any
      significant differences in academic performance between distance students and on
      campus students in clinical laboratory science. DESIGN: A quantitative causal
      comparative research design was used. SETTING: The research study was conducted
      at an academic health sciences university in the eastern United States. PATIENTS
      OR OTHER PARTICIPANTS: Anecdotal graduate data were collected from students that
      had graduated from the Clinical Laboratory Science (CLS) program. INTERVENTIONS:
      The students had either received their CLS education via distance or through the
      traditional on-campus methods. MAIN OUTCOME MEASURES: Academic performance was
      the major outcome measured. This was determined by comparing distance students'
      final grade point average (GPA) scores and certification scores to their on
      campus counterparts. RESULTS: The researchers found no significant difference in
      gender between distance and on-campus students; however, there was a significant
      difference in age. On average the distance students were older than their on
      campus counterparts. There were no significant differences found for mean overall
      admission GPA, mean math science admission GPA, mean final GPA score, and mean
      certification score. There were also no differences found in any of the
      subcategories of the certification exam except for urinalysis. For the urinalysis
      subcategory the distance students significantly outperformed their on-campus
      counterparts. Correlation studies showed that there were significant positive
      correlations between overall admission GPAs, math science admission GPAs, final
      GPA scores, and certification scores. CONCLUSIONS: The researchers have shown
      that distance learning CLS graduates are as academically prepared as their on
      campus counterparts.

PMID- 17557708
TI  - Cutaneous and systemic effects of varying doses of brown recluse spider venom in
      a rabbit model.
AB  - OBJECTIVE: To ascertain whether a dose response exists between the dose of brown
      recluse spider venom (BRSV) and the cutaneous and coagulation effects in a rabbit
      model. Cutaneous necrosis is a serious complication of brown recluse spider
      envenomation (spider bite with venom). Disseminated intravascular coagulation
      (DIC) is a dreaded complication of brown recluse envenomation in humans. New
      Zealand white (NZW) rabbits have proved to be a model for the study of
      therapeutic regimens to prevent skin necrosis after spider bites. We studied the
      venom's effects on the skin and the coagulation mechanism in this rabbit model to
      determine if a clear dose-response relationship could be established.
      Establishment of a dose-response relationship is an important first step in
      determining if the NZW rabbit is a suitable model to study both cutaneous and
      systemic effects of the venom. DESIGN: Thirty-six NZW rabbits were divided into
      three groups. One group received a saline injection, and the other two groups
      received a 4.0 microg or a 10.0 microg dose of purified BRSV intradermally into
      the skin on the dorsum of the back. METHODS: Blood was collected at baseline, 24,
      48, and 72 hours. Tissue specimens were obtained after seven days during the
      animal necropsy and gross and microscopic pathology examination was conducted to
      assess tissue damage. Measurements included complete blood count (CBC);
      platelets; PT; activated partial thromboplastin time (APTT); fibrinogen
      (clottable, immunological); coagulation factors II, V, VII, VIII, IX, X, XI, XII;
      anti-thrombin (AT); alpha-2 antiplasmin (AP); Protein C (PC); mixing studies;
      lupus anticoagulant screening; plasminogen; thrombin-antithrombin; fibrin
      degradation products (FDP); d-dimer; and thrombin time. RESULTS: Gross pathology
      results were consistent with previous studies that used higher doses of BRSV. The
      WBC and platelet counts decreased at 24 hours in the two groups receiving the
      BRSV (p < 0.05). BRSV produced a dose related prolongation in the APTT (p <
      0.05). Levels of fibrinogen as well as factors V, VII, VIII, IX, X, AT, and AP (p
      < 0.05) were increased in response to the BRSV. Protein C decreased at 24 hours
      (p < 0.05) and remained low in other time points. Mixing studies corrected the
      prolonged APTTs to normal ranges. Factor IIXI and XII showed no significant
      alteration in response to the BRSV. CONCLUSIONS: In the model, both the size and
      depth of the eschar were dose-related. We also observed a dose related elevation
      in the APTT that corrected with mixing studies. The dose-response relationship
      suggests direct interference by a component of the venom, rather than an
      idiosyncratic response. We did not detect a deficiency of commonly measured
      coagulation factors or evidence of a lupus anticoagulant. Protein C demonstrated
      a decrease. Although DIC did not occur in this rabbit model, a dose-related
      elevation in APTT was noted. The finding that the elevation corrected with mixing
      studies suggests that a plasma factor is essential in the coagulopathy associated
      with brown recluse envenomation. Further studies to identify this factor could
      shed light on human coagulopathy following envenomation.

PMID- 17557710
TI  - Applying quality improvement tools in the transfusion service.

PMID- 17557712
TI  - A few basic rules of e-mail etiquette.

PMID- 17557711
TI  - Organizing the antibody identification process.
AB  - Development of an antibody identification summary form requires input from many
      individuals and must be tailored to the requirements of a specific institution.
      This form, which provides extensive data, should be as inclusive as possible in
      compiling patient history, serological results, and implications for transfusion.
      This well-organized, comprehensive source of patient information facilitates the
      serological resolution for a patient's antibody and decreases the chances of
      organizational and communication-related errors.

PMID- 17557713
TI  - Initial assessment of a culturally tailored substance abuse prevention program
      and applicability of the risk and protective model for adolescents of Hawai'i.
AB  - BACKGROUND: Cultural interventions to decrease substance abuse must be introduced
      and evaluated. METHODS: Change in risk and protective factor ratings from a brief
      cultural school-based program were measured. RESULTS: Students demonstrated
      significant improvements in school commitment, self esteem, and perceived harm of
      drugs. These changes correlated with decreased report of drug use. DISCUSSION:
      The Ponocurriculum demonstrated effectiveness using the risk and protective
      factor model.

PMID- 17557714
TI  - Centipede bites in Hawai'i: a brief case report and review of the literature.
AB  - In this article, a local case of a centipede bite, with fairly typical symptoms
      and an uncomplicated course, is presented. The literature is reviewed, indicating
      that serious complications, while rare, are possible. The author recommends that
      clinicians structure assessments of centipede bites around knowledge of serious
      potential complications and provide counseling on prevention of future attacks.

PMID- 17557715
TI  - Intimate partner violence: systematic review of literature focused on the
      cultures of Hawai'i.
AB  - Although research on intimate partner violence (IPV) categorizes populations
      broadly; there is great diversity within the broad categories of Asian and
      Pacific Islanders. This paper reviewed the literature published between 1996 and
      2005 focused on the intersection of IPV and culture within specific cultures in
      the State of Hawai'i. The current research literature related to IPV against
      women and these specific populations is summarized.

PMID- 17557716
TI  - The role of pharmacology in medical teaching.

PMID- 17557718
TI  - Issues in medical malpractice XI. In spotting patients who may be suit-prone,
      which of the following are true?

PMID- 17557717
TI  - Tobacco smoking increases risk of colorectal cancer.

PMID- 17557720
TI  - Cancer survivorship requires long-term follow-up.

PMID- 17557719
TI  - An innovative mentoring program for Imi Ho'ola Post-Baccalaureate students at the
      University of Hawai'i John A. Burns School of Medicine.

PMID- 17557721
TI  - Issues in medical malpractice X.

PMID- 17557722
TI  - Pharmaceutical waste: environmental and regulatory considerations.

PMID- 17557723
TI  - Planning makes perfect.

PMID- 17557724
TI  - Keys of encryption.

PMID- 17557725
TI  - EHRs can boost compliance.

PMID- 17557726
TI  - The perfect marriage.

PMID- 17557727
TI  - Taking swing at better PM.

PMID- 17557728
TI  - The bigger picture.

PMID- 17557729
TI  - EMR ROI.

PMID- 17557730
TI  - Positive flow.

PMID- 17557731
TI  - Will big brother save healthcare?

PMID- 17557732
TI  - EHR pioneers try to stay out front.

PMID- 17557733
TI  - RFID and Wi-Fi square off.

PMID- 17557734
TI  - I.T. threats: obvious, unknown or hyped?

PMID- 17557735
TI  - Evidence-based I.T. in the delivery room.

PMID- 17557736
TI  - Readers perspectives. Most health care CIOs do not fully understand the cultural
      impact of new information technology implementations.

PMID- 17557737
TI  - Determination of bergenin in rat plasma by high-performance liquid
      chromatography.
AB  - A simple, sensitive, selective and reproducible reversed-phase high-performance
      liquid chromatography (HPLC) method was developed for the determination of
      bergenin in rat plasma after intravenous administration. Acetaminophen was
      successfully used, as internal standard (IS) for calibration. The chromatographic
      separation was accomplished on a reversed-phase C18 column using a mobile phase
      consisting of methanol-water (20:80, v/v, pH 2.50) and a detection wavelength of
      275 nm. Retention times of bergenin and acetaminophen were approximately 9.9 and
      6.1 min and no interfering peak of the blank plasma chromatograms was observed.
      Good linearity was achieved in the range of 0.3 - 100 microg/ml (r2 = 0.9998).
      The extraction recoveries of bergenin from plasma was 70.82%, 69.44%, 70.98% at
      concentrations of 5, 50, 100 microg/ml. Intra-assay and inter-assay variabilities
      were 0.92 - 2.60% and 2.31 - 2.95%, respectively. The accuracy was validated by
      relative error (RE%), which was in the range of -0.05 - 1.74%. The capability of
      the assay to pharmacokinetic studies was demonstrated by the determination of
      bergenin in plasma after intravenous administration to rats in doses of 7.5
      mg/kg, 15.0 mg/kg, and 30.0 mg/kg, using water as the solvent. The half-lives for
      distribution and elimination are not related to administered doses. A biphasic
      phenomenon with a rapid distribution followed by a slower elimination phase was
      observed from the plasma concentration-time curve and the pharmacokinetics was
      based on first order kinetics.

PMID- 17557738
TI  - Quantitative analysis of in vitro compatibility of binary and ternary mixtures of
      nitroimidazole and macrolides in combination with omeprazole using a calorimetric
      technique.
AB  - In the present study, in vitro interactions between nitroimidazoles, macrolides
      and omeprazole in binary and ternary mixtures were examined by measuring their
      enthalpy of solution (delta(sol)H) using a calorimetric technique. A comparison
      of the enthalpy of solution of the pure drugs with those of binary and ternary
      mixtures at pH 2 and 6 was made to indicate the magnitude of interaction between
      them. The delta(sol)H for all the nitroimidazoles is endothermic at pH 2 and 6
      but both the macrolides show exothermic behavior, whereas the enthalpy of
      solution of omeprazole changes from -40.52 to 4.35 kJmol(-1) as the pH changes
      from 2 to 6. The results have been quantified by determining the excess enthalpy
      of solution for both binary and ternary systems. The small deviations from
      ideality for all the binary systems are attributed to various non-bonding
      interactions between different functional groups on both the drug molecules. The
      results suggest compatibility of drug pairs in their binary mixtures. However,
      ternary mixtures show somewhat larger interactions. The magnitude of interaction
      enthalpy of a ternary mixture comprising tinidazole, clarithromycin and
      omeprazoles which are available as a marketed kitshas been calculated to be
      significant, suggesting that the three drugs cannot be co-formulated.

PMID- 17557739
TI  - Photodegradation and in vitro phototoxicity of aceclofenac.
AB  - Aceclofenac (Airtal) (1) is a photoallergic and phototoxic anti-inflammatory and
      analgesic agent. This drug is photolabile under aerobic and anaerobic conditions.
      Irradiation of an ethanol-solution of aceclofenac under oxygen or argon at 290
      320 nm affords via decarboxlation compound 2 as the main isolated and
      spectroscopically identified photoproduct, besides hydroxylamine derivates 3 and
      4. A radical intermediate was evidenced spectrophotometrically with GSH and DTNB,
      as well as by the dimerization of cysteine. Red blood cell lysis photosensitized
      by 1-4 was investigated. Furthermore, in a lipid-photoperoxidation test with
      linoleic acid the in vitro phototoxicity of aceclofenac was also verified. The
      photoinduced generation of peroxide by compound 1 was determined during the
      irradiation in presence of NADPH by chemiluminescence. In relation to the
      photoallergic activity of this drug, the interaction of aceclofenac with human
      serum albumin (HSA) has been studied through fluorescence spectroscopy. No
      photoinduced binding was observed after irradiation of compounds 1 in the
      presence of human serum albumin.

PMID- 17557740
TI  - Use of solid phase extraction (SPE) to evaluate in vitro skin permeation of
      aescin.
AB  - The aim of this work was to evaluate the feasibility of assessing aescin in vitro
      permeation through human skin by determining the amount of aescin permeated using
      conventional HPLC procedures after extraction of skin permeation samples by means
      of solid phase extraction (SPE). Aescin in vitro skin permeation was assessed
      from aqueous solutions and gels using both Franz-type diffusion cells and flow
      through diffusion cells. The SPE method used was highly accurate (mean accuracy
      99.66%), highly reproducible (intra-day and inter-day variations lower than 2.3%
      and 2.2%, respectively) and aescin recovery from normal saline was greater than
      99%. The use of Franz-type diffusion cells did not allow us to determine aescin
      flux values through excised human skin, therefore aescin skin permeation
      parameters could be calculated only using flow-through diffusion cells. Plotting
      the cumulative amount of aescin permeated as a function of time, linear
      relationships were obtained from both aqueous solution and gel using flow-through
      diffusion cells. Aescin flux values through excised human skin from aqueous gel
      were significantly lower than those observed from aqueous solution (p < 0.05).
      Calculating aescin percutaneous absorption parameters we evidenced that aescin
      partition coefficient was lower from the aqueous gel with respect to the aqueous
      solution. Therefore, the SPE method used in this study was suitable to determine
      aescin in vitro skin permeation parameters from aqueous solutions and gels using
      a conventional HPLC method for the analysis of the skin permeation samples.

PMID- 17557741
TI  - Ex vivo mucoadhesion and in vivo bioavailability assessment and correlation of
      ketoprofen tablet dosage forms containing bioadhesives.
AB  - The purposes of this study were to assess the mucoadhesion and bioavailability
      and their correlation for ketoprofen tablet dosage forms (F1-F6) containing
      polycarbophil (PC), sodium carboxymethylcellulose (Na CMC) as bioadhesives,
      Avicel pH 101 as direct compressible tablet vehicle or mixtures of these, and non
      compressible vehicles such as lactose and starch. For mucoadhesion assessment, we
      used sheep gastric mucosa and for bioavailability we used six human volunteers in
      an open randomized seven-way crossover study. Young's modulus (YM) and relative
      bioavailability (RB) parameters were used for evaluation of mucoadhesion and
      bioavailability, respectively. The results indicated that F2 containing Na CMC
      (72.5%) showed the highest value of YM (7.6 +/- 0.76 pascals) and 119.4 +/- 3.2%
      for RB. Decreasing the amount of Na CMC to 10% in F3 and F6 decreased the values
      of YM and RB to 1.4 +/- 0.08 and 84 +/- 2.05 in F3, 4.6 +/- 0.43 and 114.7 +/-
      2.46 in F6, respectively. The highest RB (152.3 +/- 2.56) was observed in F5
      containing starch and Avicel pH 101. This formulation showed 6 +/- 0.87 for YM.
      F4 containing PC (10%) showed 5.1 +/- 0.43 and 74.15 +/- 1.98 for YM and RB
      respectively. The lowest value of YM was observed in F1 containing Avicel pH 101
      (0.27 +/- 0.01) which also showed low RB (93.3 +/- 2.3). In conclusion,
      formulations containing bioadhesives and/or starch in high concentration showed
      high values of YM and RB which indicate good correlation between mucoadhesion and
      bioavailability. Bioadhesives may show a high potential to improve
      bioavailability and therapeutic efficacy of ketoprofen in tablet dosage forms.

PMID- 17557742
TI  - Studies on the lipophilicity of vehicles (or co-vehicles) and botanical oils used
      in cosmetic products.
AB  - The lipophilic character of five vehicles (or co-vehicles): diethylhexylmaleate,
      dimethicone, light mineral oil, octyldodecanol and oleyl alcohol and eight
      botanical oils: Aloe vera oil, coconut oil, extra virgin olive oil, grape leaf
      oil, grape seed oil, hazelnut oil, jojoba oil and safflower oil was determined by
      partitioning esters of p-hydroxybenzoic acid (parabens) between them and
      phosphate buffer (pH 7.4). The results were compared to those obtained with 1
      octanol. The most lipophilic effects were observed with octyldodecanol and oleyl
      alcohol for the vehicles (or co-vehicles), coconut oil, jojoba oil and safflower
      oil for botanical oils. Light mineral oil showed the least lipophilic effect.
      With butylparaben, it was observed that oleyl alcohol, octyldodecanol, coconut
      oil and jojoba oil were 0.94, 0.91, 0.74 and 0.68 times as lipophilic as 1
      octanol respectively. The study indicates that octyldodecanol and oleyl alcohol
      could be good substitutes for 1-octanol in partition coefficient determination.
      The estimated permeability coefficients of the parabens suggest that
      octyldodecanol, oleyl alcohol, coconut oil and jojoba oil could be potential
      dermal permeation enhancers.

PMID- 17557743
TI  - Nanocapsules, nanoemulsion and nanodispersion containing melatonin: preparation,
      characterization and stability evaluation.
AB  - In a previous work, we have demonstrated that melatonin-loaded polymeric
      nanoparticles provided an important increase in the antioxidant effect of
      melatonin against lipid peroxidation. Hence, in this work, the aim was to study
      the stability of nanocapsules containing melatonin (1.5 mg/mL) prepared by
      interfacial deposition, using different polymers. For comparison, the stability
      of the nanoemulsion and nanodispersion was also evaluated. These nanoparticulated
      systems had diameters between 134 and 325 nm. The associated melatonin
      concentrations ranged from 29% to 50%, depending on the composition of the
      nanocarriers. The stability evaluation of formulations was preformed at room
      temperature and protected from or exposed to the natural light or at 50 degrees C
      and protected from the light. The stability of the nanocarriers was evaluated in
      terms of the macroscopic aspects, the total contents of melatonin, associated
      melatonin concentrations, pH and sizes of particles. The compositions of the
      nanocarriers and the condition of storage influenced the stability of melatonin.

PMID- 17557744
TI  - Development of HPMC and Eudragit S100 blended microparticles containing sodium
      pantoprazole.
AB  - Pantoprazole is used in the treatment of acid related disorders and Helicobacter
      pylori infections. It is activated inside gastric parietal cells binding
      irreversibly to the H+/K(+)-ATPase. In this way, pantoprazole must be absorbed
      intact in gastro-intestinal tract, indicating that enteric delivery systems are
      required. The purpose of this study was to prepare pantoprazole-loaded
      microparticles by spray-drying using a blend of Eudragit S100 and HPMC, which can
      provide gastro-resistance and controlled release. Microparticles presented
      acceptable drug loading (120.4 mgg(-1)), encapsulation efficiency (92.3%),
      surface area (49.0 m2g(-1)), and particle size (11.3 microm). DSC analyses showed
      that the drug is molecularly dispersed in the microparticles, and in vivo anti
      ulcer evaluation demonstrated that microparticles were effective in protecting
      stomach against ulceration. Microparticles were successfully tabletted using
      magnesium stearate. In vitro gastro-resistance study showed that microparticles
      stabilized pantoprazole in 62.0% and tablets in 97.5% and provided a controlled
      release of the drug.

PMID- 17557745
TI  - Prediction of drug solubility in water-propylene glycol mixtures using Jouyban
      Acree model.
AB  - A trained version of the Jouyban-Acree model was presented to predict drug
      solubility in water-propylene glycol mixtures at various temperatures. The model
      is able to predict the solubility in various solubility units and requires the
      experimental solubility of a solute in mono-solvent systems. The mean percentage
      deviation (MPD) of predicted solubilities was computed to show the accuracy of
      the predicted data and 24% was found as the average MPD for 27 data sets studied.
      The proposed model enables the researchers to predict solubiliy in water
      propylene glycol mixtures at various temperatures and reduces the number of
      required experimental data from five to two points.

PMID- 17557746
TI  - Influence on intestinal mucous permeation of paclitaxel of absorption enhancers
      and dosage forms based on electron spin resonance spectroscopy.
AB  - The aim of this paper is to investigate the permeation mechanism of the
      hydrophobic drug, paclitaxel in intestinal membranes of mice in relation to
      enhancers and preparation factors. The alteration fluidity of lipid and protein
      in mucous membrane were determined using electron spin resonance (ESR) when the
      membrane was treated with several enhancers including Pluronic F68, polyethylene
      glycol (PEG), Brij78 and lecithin. At the same time, the enhanced permeation of
      paclitaxel across the intestinal intercellular membrane of stratum corneum was
      studied for three formulations: inclusion complex, microemulsion and injection.
      The results showed that use of paclitaxel-hydroxypropyl-beta-cyclodextrin
      inclusion complexation and of paclitaxel microemulsion as vehicle and PEG 1500 as
      enhancer could significantly increase the permeation kinetics of paclitaxel in a
      fluid diffusion study. The effect on absorption characteristics of enhancing
      permeation of this hydrophobic drug in the intestinal mucosa was considered in
      the light of the change in membrane fluid.

PMID- 17557747
TI  - Preparation of the traditional Chinese medicine compound recipe Shuxiong
      sustained-release capsules by multiparticulate time-controlled explosion
      technology.
AB  - In this study the traditional Chinese medicine compound recipe (TCMCR) Shuxiong
      sustained-release capsules (SXSRC) were prepared by multiparticulate time
      controlled explosion technology. First, Shuxiong pellets were prepared with the
      refined medicinal materials containing in the recipe of Shuxiong tablets. Then,
      the pellets were coated sequentially with an inner swelling layer containing low
      substituted hydroxypropylcellulose as the swelling agent and an outer rupturable
      layer of ethylcellulose. Finally, SXSRC were developed by encapsulating five
      kinds of pellets whose respective coating level of outer layer was 0%, 9%, 15%,
      18% and 20% at equivalent ratio in hard gelatin capsules. Under the simulated
      gastrointestinal pH conditions, the in vitro release test of SXSRC was carried
      out. The value of similarity factor (f2) of hydroxysafflor yellow A and Panax
      notoginseng saponins, hydroxysafflor yellow A and ferulic acid, Panax notoginseng
      saponins and ferulic acid was 90.1, 77.3, 87.0, respectively. The release
      profiles of these three compositions from SXSRC showed a characteristic of
      obvious sustained-release and no significant difference between them. The results
      indicated that using multiparticulate time-controlled explosion technology
      various components in TCMCR with vastly different physicochemical properties
      could be released synchronously while sustained-releasing. That complies with the
      organic whole conception of compound compatibility of TCMCR.

PMID- 17557748
TI  - Effects of phytoestrogens and 17beta-estradiol on vasoconstriction elicited by
      reactive oxygen species.
AB  - To study the effects of different reactive oxygen species (ROS) on the resting
      tension of porcine coronary artery rings and to identify the effects of genistein
      (GEN), resveratrol (RES) and 17beta-estradiol (EST) on ROS-elicited
      vasoconstriction, porcine coronary rings were prepared and mounted in an organ
      bath and, after an equilibration period, the changes induced by the drugs were
      observed. Rings with intact endothelium showed an obvious but slow contraction
      after treatment with xanthine (100 microM)/xanthine oxidase (20 mU x mL(-1))
      (X/XO) whereas endothelium-denuded rings showed no effects. H2O2 (200 microM)
      induced a fast and transient contraction in endothelium-denuded rings and failed
      to do so in intact-endothelium rings. Like superoxide dismutase (SOD, 200 U x mL(
      1)), GEN (1 microM) and RES (1 microM) significantly inhibited contractile
      response evoked by X/XO, however in contrast to GEN and RES, EST (1 microM) had
      no obvious effect. GEN (30 microM) and RES (30 microM), like catalase (CAT, 800 U
      x mL(-1)), markedly attenuated the contraction elicited by H2O2. The results
      demonstrate that GEN and RES have distinct inhibitory effects on vasoconstriction
      induced by O2*- generated by X/XO and H2O2, and their actions are clearly greater
      than to that of EST.

PMID- 17557749
TI  - Biochemical study on the protective potential of Nardostachys jatamansi extract
      on lipid profile and lipid metabolizing enzymes in doxorubicin intoxicated rats.
AB  - Nardostachys jatamansi is a medicinally important herb of Indian origin used for
      centuries in Ayurvedic and Unani systems of medicine for the treatment of various
      ailments. The aim of the present work is to evaluate the effect of ethanolic
      extract of Nardostachys jatamansi rhizomes on doxorubicin induced myocardial
      injury with respect to lipid metabolism in serum and heart of Wistar albino rats.
      Altered lipid metabolism alters the cardiac function which is mainly due to
      changes in the property of the cardiac cell membrane. Doxorubicin exhibits
      cardiotoxicity by inhibition of fatty acid oxidation in the heart. The rats
      treated with a single dose of doxorubicin (15 mg/kg) intraperitoneally showed an
      increase in serum and cardiac lipids (cholesterol, triglycerides, free fatty
      acids and phospholipids), along with a significant rise in serum low density
      lipoproteins (LDL), very low density lipoproteins (VLDL) and drop in high density
      lipoproteins (HDL) levels, resulting in alteration of serum and cardiac lipid
      metabolizing enzymes. Pretreatment with a extract of Nardostachys jatamansi (500
      mg/kg) orally for seven days to doxorubicin induced rats showed a significant
      prevention in the lipid status with the activities of the lipid metabolizing
      enzymes. Histopathological observations were also in correlation with the
      biochemical parameters. These findings suggest that the protective and
      hypolipidemic effect of Nardostachys jatamansi against doxorubicin induced
      myocardial injury in rats could possibly be mediated through its anti lipid
      peroxidative properties.

PMID- 17557750
TI  - Icariin inhibits the osteoclast formation induced by RANKL and macrophage-colony
      stimulating factor in mouse bone marrow culture.
AB  - Icariin is a prenylated flavonol glycoside contained in the herb Epimedium, which
      has long been used to improve bone fracture healing or prevent osteoporosis
      because of the belief that the herb has bone-strengthening action. We have
      previously demonstrated that icariin enhances the osteogenic differentiation of
      rat bone marrow stromal cells, and partially explained the bone-strengthening
      mechanism of the herb. In the present study, the effect of icariin on
      osteoclastogenesis and bone resorption activity was investigated in mouse bone
      marrow culture. It was found that icariin dose-dependently inhibited the growth
      and differentiation of hemopoietic cells from which osteoclasts were formed. Far
      less TRAP+ multinuclear cells appeared in the 10 microM icariin group than in the
      control. The bone resorption pits formed in the 10 microM icariin group was also
      significantly less than that of the control. RT-PCR analysis showed that the gene
      expression of TRAP, RANK and CTR was obviously lower than that of the control. It
      can be concluded that icariin has the ability to inhibit the formation and bone
      resorption activity of osteoclasts, which suggests that icariin should be the
      effective component for the bone-strengthening action of herb Epimedium.

PMID- 17557751
TI  - Brassinolide, a plant sterol from pollen of Brassica napus L., induces apoptosis
      in human prostate cancer PC-3 cells.
AB  - Brassinolide is a plant sterol first isolated from pollen of rape (Brassica napus
      L.). The present study was carried out to investigate the effect of brassinolide
      on androgen-independent human prostate cancer PC-3 cell viability. Results showed
      that brassinolide could induce a time and concentration-dependent cytotoxicity in
      PC-3 cells. The mode of cell death appeared to be predominately apoptosis, as
      shown by flow-cytometric analysis, fluorescence and transmission electron
      microscopes. Caspase-3 activity was obviously increased after brassinolide
      treatment. Western blot studies indicated that treatment with brassinolide
      triggered a time-dependent decrease in the expression of anti-apoptotic protein
      Bcl-2. We suggest that brassinolide could induce cytotoxicity in PC-3 cells by
      triggering apoptosis. Brassinolide might therefore be a promising candidate for
      the treatment of prostate cancer.

PMID- 17557752
TI  - Characterization of the pungent principles and the essential oil of Zanthoxylum
      schinifolium pericarp.
AB  - The pungent principles and the essential oil from the pericarp of Zanthoxylum
      schinifolium (Rutaceae) have been investigated and compared to those of Z.
      bungeanum, the primary source of the traditional Chinese drug Huajiao
      (Pericarpium Zanthoxyli). HPLC-MS and HPLC-NMR analyses revealed an alkylamide
      profile highly similar to that of Z. bungeanum, with hydroxy-alpha-sanshool and
      hydroxy-beta-sanshool being in both plants the major constituents of the
      alkylamide fraction. GC-FID and GC-MS analyses of the essential oil showed that
      limonene was, like in Z. bungeanum, the main component (21%), followed by 4
      terpineol, gamma-terpinene, alpha-terpineol acetate, beta-pinene, alpha-terpineol
      and beta-linalool.

PMID- 17557753
TI  - [Spontaneous liver haemorrhage during pregnancy: a rare and life-threatening
      situation].
AB  - Three pregnant women, of whom 2 were 33 and 1 was 35 years of age, were seen; 2
      of them had upper abdominal pain and 1had oedema. All had proteinuria and liver
      enzyme abnormalities, and pre-eclampsia or the HELLP syndrome was suspected. They
      were consequently admitted and at first treated with antihypertensive agents. One
      patient underwent a Caesarean section and the baby had a good start. Afterwards,
      however, the patient developed shock. A CT-scan revealed a hepatic rupture, for
      which repeated surgical packing of the liver was carried out. The postoperative
      course was complicated. A second patient developed shock and the foetus died.
      Here the CT-scan revealed a liver haematoma. At surgery the next day, removal of
      the foetus was followed by heavy uterine bleeding. The patient again developed
      shock and the uterus was resected. A haematoma that was seen in the liver was
      treated expectatively. The postoperative course was not complicated. In a third
      patient, abdominal echography revealed bleeding from the liver. Simultaneous
      Caesarean section and surgical exploration of the liver took place, with packing
      of the liver. The child had Apgar scores of 4, 7 and 9. After re-laparotomy
      because of persistent bleeding from the liver the patient recovered. Spontaneous
      liver haemorrhage and hepatic rupture during pregnancy is a rare condition
      associated with significant maternal and perinatal mortality. The majority of
      cases occur during pregnancies complicated by pre-eclampsia or the HELLP
      syndrome. The presenting symptoms are non-specific. A high index of suspicion is
      important and early evaluation with imaging is necessary to improve the prognosis
      of both mother and child.

PMID- 17557754
TI  - [Postoperative cognitive dysfunction].
AB  - Memory loss and lack of concentration are symptoms that frequently occur in
      patients who have undergone a surgical procedure. Although cognitive function can
      be assessed using neuropsychological tests, diagnosing postoperative cognitive
      decline (POCD) reliably appears to be difficult. Therefore, the true incidence of
      POCD is unknown. Severe POCD, which is apparent even without neuropsychological
      testing, is predominantly reported after cardiac and hip-replacement surgery. In
      these cases, POCD probably reflects micro embolic brain injury. Apart from the
      nature of the surgical procedure, advanced age is the most important risk factor
      for POCD. The anaesthetic technique used is not a determinant: the risks of POCD
      occurring appear to be similar following both general and local anaesthesia.

PMID- 17557755
TI  - [The value of PET-CT imaging in malignant tumours of the head and neck].
AB  - Imaging with fluor-18-deoxyglucose(FDG)-positron-emission tomography (PET) and CT
      combined in a single machine is a recent development. Using this technique both
      molecular and anatomical information are acquired. This results in an increased
      sensitivity and specificity in comparison to PET and CT as a single modality. One
      of the main advantages is that interpretation of PET images can be related to the
      anatomical information which helps to delineate the size and extent of a tumour
      as well as its relationship with surrounding tissues. It is also useful in
      planning surgical treatment and irradiation. At restaging PET-CT delineates the
      site and extent of a recurrence in the complex anatomy of the head and neck
      region and helps to define the location of a biopsy. This is particularly
      valuable in the anatomically complex head and neck region. Whole-body imaging can
      detect distant metastases and second primary tumours. PET-CT has the potential to
      become a part of the staging procedure of the primary tumour and also the follow
      up in patients who have been treated for head and neck cancer.

PMID- 17557756
TI  - [Diagnostic image (325). A traveller with a chronic wound].
AB  - A 43-year-old man with a chronic leg ulcer was diagnosed with Buruli-ulcer,
      caused by Mycobacterium ulcerans, probably contracted in Australia.

PMID- 17557757
TI  - [From gene to disease: adrenogenital syndrome and the CYP21A2 gene].
AB  - Congenital adrenal hyperplasia (CAH) is a disorder of adrenal steroid synthesis.
      In more than 90% of cases CAH is caused by CYP21 (21-hydroxylase) deficiency
      leading to impaired cortisol and aldosterone synthesis and an increase in ACTH
      secretion. This then leads to stimulation of the adrenal gland and overproduction
      of androgens with virilisation of female external genitalia. The CYP21 enzyme
      consists of 495 amino acids and is encoded by the CYP21A2 gene located on
      chromosome 6p21.3 close to a 98% homologous pseudogene (CYP21p). The pseudogene
      contains several inactivating mutations that may be transferred to the active
      CYP21A2 gene by gene conversion (more than 60% of the affected alleles) or gene
      deletion (30% of the affected alleles). The severity of the disease depends on
      the degree of CYP21 deficiency. The diagnosis can be made by measuring levels of
      17-hydroxyprogesterone and androstenedione in serum.

PMID- 17557758
TI  - [Alendronate more effective than alfacalcidol in the prevention of osteoporosis
      in patients with rheumatic disease who are starting glucocorticoid therapy].
AB  - OBJECTIVE: To compare the effects of alendronate and alfacalcidol in the
      prevention ofglucocorticoid-related osteoporosis in patients with a rheumatic
      disease. DESIGN: Randomised, double-blind, double-placebo clinical trial (www.
      clinicaltrials.gov; number: NCT00138983). METHODS: A total of 201 patients with
      rheumatic disease who were starting glucocorticoid treatment at a daily dose that
      was equivalent to at least 7.5 mg of prednisone were randomised to alendronate
      (10 mg) and a placebo capsule ofalfacalcidol daily (n = 100) or alfacalcidol (1
      microg) and a placebo tablet ofalendronate daily (n = 101) for 18 months. Primary
      outcome was change in lumbar spine bone mineral density at 18 months. The main
      secondary outcome was the incidence of morphometrically confirmed vertebral
      deformities. RESULTS: Overall, 163 patients completed the study. The bone mineral
      density of the lumbar spine increased by 2.1% (95% CI: 1.1-3.1) in the
      alendronate group and decreased by 1.9% (95% CI: -3.I--0.7) in the alfacalcidol
      group. At 18 months the mean difference in change in bone mineral density between
      the two groups was 4.0% (95% CI: 2.4-5-5). Three patients in the alendronate
      group had a new vertebral deformity, compared with 8 patients in the alfacalcidol
      group, including 5 symptomatic vertebral fractures in 3 patients; the hazard
      ratio was 0.4 (95% CI: 0.1-1.4). CONCLUSION: Alendronate was more effective than
      alfacalcidol in preventing glucocorticoid-induced bone loss during this 18-month
      trial in patients with rheumatic diseases who were starting glucocorticoid
      treatment.

PMID- 17557759
TI  - [Multiple emboli from a cardiac metastasis of a renal-cell carcinoma].
AB  - A 68-year-old man was hospitalised with a vascular occlusion in the left leg.
      After treatment with urokinase he developed multiple intracerebral haemorrhages.
      The occlusion and the intracerebral haemorrhages evoked by urokinase were caused
      by embolisation originating from a cardiac metastasis of a renal-cell carcinoma.
      Cardiac surgery was performed, but complete removal of the tumour was not
      possible. The process of embolisation continued and the patient died a few weeks
      after diagnosis. Cardiac metastasis is seen in 10% of all cancer patients. Most
      of these metastases remain without symptoms. Left ventricular metastasis of renal
      cell carcinoma without involvement of the inferior V. cava is very rare. If
      embolic occlusion of one or more vascular areas is present, transthoracic
      echography of the heart should be performed. Early detection and surgical
      treatment prevent further embolisation which may result in a better prognosis.

PMID- 17557760
TI  - [Lactic acidosis and accumulation of glutamate in the blood of neonates following
      treatment with calcium levulinate for hypocalcaemia].
AB  - The data from 5 clinics concerning 8 infants, who had developed severe lactic
      acidosis and hyperglutamic acidaemia were reviewed. Blood-lactate levels were up
      to 15 mmol/l (reference level: < 2) and plasma-glutamate levels up to 1632 pmol/l
      (reference level: 14-78), and there was no concomitant hyperglutaminaemia (levels
      up to 1032 micromol/l (reference level: 333-809)). A positive correlation between
      the amount of calcium levulinate administered and the degree of hyperglutamic
      acidaemia was found. Replacement of the calcium levulinate by another calcium
      salt caused a reversal of the biochemical abnormalities of the patients. Two of
      the infants had a 22q11 microdeletion. This development of severe acidosis in
      infants who had been given a calcium supplement in the form of calcium levulinate
      may be related to genetic predisposition. The paradoxal hyperketonaemia and
      generalized aminoaciduria in 4 other patients suggested disturbed function ofthe
      mitochondrial respiratory chain. The hypothesis of the occurrence of an
      underlying defect of the mitochondrial respiratory chain was tested in the muscle
      tissue of one 22q11 patient, but this showed no abnormalities. Excessive
      accumulation of glutamate because of dysfunction ofglutamine synthetase, which
      forms glutamate from glutamine seems unlikely because of the relatively low
      values of plasma glutamate compared to the glutamine plasma levels. Calcium
      levulinate should no longer be used in neonates as it may lead to lactic
      acidosis.

PMID- 17557761
TI  - [Settlement effected for damages for victims of diethylstilbestrol (DES)].
AB  - In 2007 the Dutch DESFonds (DES Fund) starts payment to victims of exposure to
      diethylstilbestrol in a collective settlement. This is unique in the world
      because the arrangement covers the entire range of DES-related disorders and
      individual persons do not have to start an expensive and emotionally taxing legal
      procedure with uncertain outcome, which would last several years. Individuals can
      now be compensated based on medical evidence of DES exposure and the presence of
      a DES-related disorder covered by the settlement. In close collaboration with the
      DES Centre (an association of DES victims) a careful procedure was followed
      before this settlement was realised. The Dutch Expert Committee on DES-related
      Health Effects first reviewed the literature for evidence and established a list
      of disorders with a causal association with DES. For each DES-related disorder
      covered by the settlement, the appropriate compensation was determined by the
      attributive risk and the severity of the disease. The settlement is the result of
      close collaboration between all parties involved.

PMID- 17557762
TI  - [Functional imaging of the brain in the investigation of chronic unexplained
      pain].

PMID- 17557763
TI  - [Functional imaging of the brain in the investigation of chronic unexplained
      pain].

PMID- 17557764
TI  - Proteomic analysis of human ovaries from normal and polycystic ovarian syndrome.
AB  - Polycystic ovary syndrome (PCOS) is the most common cause of anovulatory
      infertility, affecting 5-10% of females of reproductive age. Currently, little is
      known about the changes in whole proteins between PCOS and normal ovaries. In the
      present study, a proteomic approach comprised two-dimensional gel electrophoresis
      (2DE) analysis and mass spectroscopy was used to identify proteins and examine
      expression patterns in three PCOS and normal ovaries. One hundred and ten protein
      spots were separated and showed different intensities between PCOS and normal
      ovaries. Sixty-nine proteins associated with cellular metabolism and
      physiological process were identified from 72 spots. Fifty-four proteins were up
      regulated in PCOS ovaries and 15 other proteins were up-regulated in normal
      ovaries. These data demonstrate, for the first time, the complexity in the
      regulation of ovarian protein expression in human PCOS, and will provide
      important insight for a better understanding of the pathogenetic mechanisms
      underlying this clinical disorder.

PMID- 17557765
TI  - Amino acid quantitative structure property relationship database: a web-based
      platform for quantitative investigations of amino acids.
AB  - Here, we present the AA-QSPR Db (Amino Acid Quantitative Structure Property
      Relationship Database): a novel, freely available web-resource of data pertaining
      to amino acids, both engineered and naturally occurring. In addition to
      presenting fundamental molecular descriptors of size, charge and hydrophobicity,
      it also includes online visualization tools for users to perform instant,
      interactive analyses of amino acid sub-sets in which they are interested. The
      database has been designed with extensible markup language technology to provide
      a flexible structure, suitable for future development. In addition to providing
      easy access for queries by external computers, it also offers a user-friendly web
      based interface that facilitates human interactions (submission, storage and
      retrieval of amino acid data) and an associated e-forum that encourages users to
      question and discuss current and future database contents.

PMID- 17557766
TI  - Concurrent mutations in six amino acids in beta-glucuronidase improve its
      thermostability.
AB  - To achieve a thermostable beta-glucuronidase (GUS) and identify key mutation
      sites, we applied in vitro directed evolution strategy through DNA shuffling and
      obtained a highly thermostable mutant GUS gene, gus-tr, after four rounds of DNA
      shuffling and screening. This variant had mutations in 15 nucleic acid sites,
      resulting in changes in 12 amino acids (AAs). Using gus-tr as the template, we
      further performed site-directed mutagenesis to reverse the individual mutation to
      the wild-type protein. We found that six sites (Q493R, T509A, M532T, N550S, G559S
      and N566S) present in GUS-TR3337, were the key AAs needed to confer its high
      thermostability. Of these, Q493R and T509A were not reported previously as
      important residues for thermostability of GUS. Furthermore, all of these six
      mutations must be present concurrently to confer the high thermostability. We
      expressed the gus-tr3337 gene and purified the GUS-TR3337 protein that contained
      the six AA mutations. Compared with the wild-type protein which lost its activity
      completely after 10 min at 70 degrees C, the mutant GUS-TR3337 protein retained
      75% of its activity when heated at 80 degrees C for 10 min. The GUS-TR3337
      exhibited high activity even heated at 100 degrees C for 30 min on nitrocellulose
      filter. The comparison of molecular models of the mutated and wild-type enzyme
      revealed the relation of protein function and these structural modifications.

PMID- 17557767
TI  - Electrogram-guided isolation of the left superior vena cava for treatment of
      atrial fibrillation.
AB  - AIMS: Radiofrequency ablation targeting the pulmonary veins offers potential cure
      for patients with symptomatic paroxysmal atrial fibrillation (AF). Initiating
      ectopics can also arise from other sites including the major thoracic veins, vein
      of Marshall and more rarely, persistent left superior vena cava (LSVC). We report
      our experience with arrhythmogenic persistent LSVC initiating AF. METHODS AND
      RESULTS: The LSVC was present in four patients from an overall series of 204
      patients undergoing AF ablation at our centre. All were males, mean age 50 +/- 11
      years. All patients underwent pre-procedure transesophageal echocardiography. The
      mapping of the LSVC was performed with a circumferential mapping catheter
      following pulmonary vein isolation. Atrial ectopics from the LSVC were observed
      to initiate AF. Catheter ablation (power controlled mode; 65 degrees C and 30 W
      at irrigation flow rate of 30 mL/min) resulted in electrical isolation of the
      LSVC in all patients and was accompanied by termination of AF in one of four
      patients. There were no complications. All patients underwent multiple procedures
      (three procedures in one patient, two procedures in three patients). After a mean
      follow-up of 18 +/- 7 months (range 7-24 months), three of the four patients
      remained free of AF off antiarrhythmic medications. CONCLUSION: Arrhythmogenic
      foci within persistent LSVC can result in AF despite electrical isolation of
      pulmonary veins. This report demonstrates the importance of the LSVC as a
      potential source of atrial ectopics initiating and perpetuating AF.

PMID- 17557768
TI  - Acute and chronic effects of cardiac resynchronization in patients developing
      heart failure with long-term pacemaker therapy for acquired complete
      atrioventricular block.
AB  - AIMS: We assessed the effects of cardiac re-synchronization therapy (CRT) in
      patients who developed otherwise unexplained heart failure (HF) during right
      ventricular apical (RVA)-pacing for acquired complete atrioventricular block
      (CAVB). METHODS AND RESULTS: Eighteen consecutive CAVB patients with HF during
      RVA-pacing were assessed with haemodynamic studies immediately and 12 months
      after CRT-upgrade. Ten patients had idiopathic CAVB and 13 showed normal left
      ventricular (LV) function at RVA-pacemaker implantation. HF developed after 81 +/
      10 months. RVA-pacing duration correlated (r = 0.49, P < 0.05) with LV ejection
      fraction (LVEF) deterioration. Biventricular- (BiV) and LV-pacing acutely
      improved the systolic function comparably, but only BiV improved diastolic
      function. One-year post-CRT-initiation, New York Heart Association classification
      improved 35 +/- 3% (P < 0.05) and the number of hospitalizations decreased 85 +/-
      3% (P < 0.0001). CRT decreased LV end-diastolic diameter (LVEDd) 7 +/- 2% (P <
      0.01) and increased LVEF by 23 +/- 7% (P < 0.01). The CRT-induced reduction in
      LVEDd tended to be greater in patients with RVA-pacing for < 5 years vs. > 5
      years (7.7 +/- 2.5 vs. 3.6 +/- 1.0 mm, P = 0.08). CONCLUSION: CRT-upgrade
      improves the cardiac function and symptoms in CAVB patients with HF progression
      related to RVA-pacing. Because adverse LV-remodelling may be partly irreversible,
      consideration should be given to BiV- and LV-pacing upgrade as soon as possible
      after the indications appear, and prospective studies of the optimal timing of
      CRT-upgrade may be useful.

PMID- 17557770
TI  - Interstitial lung disease and anti-Jo-1 antibodies: difference between acute and
      gradual onset.
AB  - AIM: A multicentre retrospective study was undertaken to examine patients with
      interstitial lung disease (ILD) with the initial clinical manifestation of an
      anti-synthetase syndrome (anti-Jo-1 antibodies), and to analyse the
      characteristics and long-term outcome of these patients according to their
      clinical presentation (acute or gradual onset), treatment and adverse events
      related to treatment. METHODS: 32 patients, 15 (47%) presenting with acute onset
      and associated respiratory insufficiency (group A) and 17 (53%) with gradual
      onset (group G) were examined. Myositis was diagnosed at admission in only 31% of
      cases and was observed during follow-up in 56% of cases, but the prevalence did
      not differ between the two groups. RESULTS: Fever and radiological patterns
      including diffuse patchy ground-glass opacities, basal irregular lines and
      consolidation on high-resolution CT scan were more frequent in group A than in
      group G. More patients in group G had neutrophils in the bronchoalveolar lavage
      fluid and autoantibodies other than anti-Jo-1 (rheumatoid factor, anti SSa/SSb)
      than in group A. The percentage of patients in whom the ILD improved at 3 months
      was significantly higher in group A than in group G (13/15 vs 9/17; p = 0.006).
      In contrast, after 12 months, most patients with ILD progression were in group A
      and were treated with corticosteroids alone. A combination of corticosteroids and
      an immunosuppressive drug was required in most cases (84%) at the end of the
      follow-up period. Severe adverse effects of treatment were observed and varicella
      zoster virus infection was frequent. CONCLUSIONS: Early testing for anti
      synthetase antibodies, particularly anti-Jo-1, and creatine kinase determination
      are useful procedures in patients presenting with ILD. Treatment with
      corticosteroids and immunosuppressive drugs is required in most patients. At the
      end of the study, around two-thirds of patients had stable ILD while the other
      third had disease progression with respiratory insufficiency.

PMID- 17557769
TI  - Effect of CPAP on insulin resistance and HbA1c in men with obstructive sleep
      apnoea and type 2 diabetes.
AB  - BACKGROUND: The effects of continuous positive airway pressure (CPAP) for
      obstructive sleep apnoea (OSA) on insulin resistance are not clear. Trials have
      found conflicting results and no appropriate control groups have been used.
      METHODS: Forty-two men with known type 2 diabetes and newly diagnosed OSA (>10
      dips/h in oxygen saturation of >4%) were randomised to receive therapeutic (n =
      20) or placebo CPAP (n = 22) for 3 months. Baseline tests were performed and
      repeated after 3 months. The study was double blind. RESULTS: Results are
      expressed as mean (SD). CPAP improved the Epworth sleepiness score significantly
      more in the therapeutic group than in the placebo group (-6.6 (4.5) vs -2.6
      (4.9), p = 0.01). The maintenance of wakefulness test improved significantly in
      the therapeutic group but not in the placebo group (+10.6 (13.9) vs -4.7 (11.8)
      min, p = 0.001). Glycaemic control and insulin resistance did not significantly
      change in either the therapeutic or placebo groups: HbA1c (-0.02 (1.5) vs +0.1
      (0.7), p = 0.7, 95% CI -0.6% to +0.9%), euglycaemic clamp (M/I: +1.7 (14.1) vs 
      5.7 (14.8), p = 0.2, 95% CI -1.8 to +0.3 l/kg/min(1000)), HOMA-%S (-1.5 (2.3) vs 
      1.1 (1.8), p = 0.2, 95% CI -0.3% to +0.08%) and adiponectin (-1.1 (1.2) vs -1.1
      (1.3), p = 0.2, 95% CI -0.7 to +0.6 microg/ml). Body mass index, bioimpedance and
      anthropometric measurements were unchanged. Hours of CPAP use per night were 3.6
      (2.8) in the treatment group and 3.3 (3.0) in the placebo group (p = 0.8). There
      was no correlation between CPAP use and the measures of glycaemic control or
      insulin resistance. CONCLUSION: Therapeutic CPAP does not significantly improve
      measures of glycaemic control or insulin resistance in men with type 2 diabetes
      and OSA.

PMID- 17557771
TI  - Effect of salmeterol/fluticasone propionate on airway inflammation in COPD: a
      randomised controlled trial.
AB  - BACKGROUND: Airway inflammation in chronic obstructive pulmonary disease (COPD)
      is characterised by infiltration of CD8+ T cells and CD68+ macrophages and an
      increased number of neutrophils, whereas few studies have described the presence
      of eosinophils. Although the anti-inflammatory effects of corticosteroids in
      stable COPD are unclear, recent studies suggest that combination therapy could be
      beneficial. A study was therefore undertaken to evaluate combined
      salmeterol/fluticasone propionate (SFC) and fluticasone propionate (FP) alone on
      inflammatory cells in the airways of patients with COPD. METHODS: Patients were
      treated in a randomised, double blind, parallel group, placebo-controlled trial
      with either a combination of 50 microg salmeterol and 500 microg FP twice daily
      (SFC, n = 19, 19 men, mean age 62 years), 500 microg FP twice daily (n = 20, 15
      men, mean age 64 years) or placebo (n = 21, 17 men, mean age 66 years) for 3
      months. At the start and end of treatment bronchoscopy with bronchial biopsies
      was performed and the numbers of CD8+ T lymphocytes, CD68+ macrophages,
      neutrophils and eosinophils were measured. RESULTS: CD8+ cells were significantly
      reduced by SFC compared with placebo (difference -98.05 cells/mm(2); 95% CI 
      143.14 to -52.9; p<0.001). Such a marked effect was not seen with FP alone (
      44.67 cells/mm(2); 95% CI -90.92 to 1.57; p = 0.06). CD68+ macrophages were also
      reduced by SFC compared with placebo (difference -31.68 cells/mm(2); 95% CI 
      61.07 to -2.29; p = 0.03) but not by FP. SFC did not significantly change
      neutrophils and eosinophils compared with placebo. CONCLUSIONS: SFC has airway
      anti-inflammatory effects not seen with inhaled corticosteroids alone.

PMID- 17557772
TI  - The value of multiple tests of respiratory muscle strength.
AB  - BACKGROUND: Respiratory muscle weakness is an important clinical problem. Tests
      of varying complexity and invasiveness are available to assess respiratory muscle
      strength. The relative precision of different tests in the detection of weakness
      is less clear, as is the value of multiple tests. METHODS: The respiratory muscle
      function tests of clinical referrals who had multiple tests assessed in our
      laboratories over a 6-year period were analysed. Thresholds for weakness for each
      test were determined from published and in-house laboratory data. The patients
      were divided into three groups: those who had all relevant measurements of global
      inspiratory muscle strength (group A, n = 182), those with full assessment of
      diaphragm strength (group B, n = 264) and those for whom expiratory muscle
      strength was fully evaluated (group C, n = 60). The diagnostic outcome of each
      inspiratory, diaphragm and expiratory muscle test, both singly and in
      combination, was studied and the impact of using more than one test to detect
      weakness was calculated. RESULTS: The clinical referrals were primarily for the
      evaluation of neuromuscular diseases and dyspnoea of unknown cause. A low maximal
      inspiratory mouth pressure (Pimax) was recorded in 40.1% of referrals in group A,
      while a low sniff nasal pressure (Sniff Pnasal) was recorded in 41.8% and a low
      sniff oesophageal pressure (Sniff Poes) in 37.9%. When assessing inspiratory
      strength with the combination of all three tests, 29.6% of patients had weakness.
      Using the two non-invasive tests (Pimax and Sniff Pnasal) in combination, a
      similar result was obtained (low in 32.4%). Combining Sniff Pdi (low in 68.2%)
      and Twitch Pdi (low in 67.4%) reduced the diagnoses of patients with diaphragm
      weakness to 55.3% in group B. 38.3% of the patients in group C had expiratory
      muscle weakness as measured by maximum expiratory pressure (Pemax) compared with
      36.7% when weakness was diagnosed by cough gastric pressure (Pgas), and 28.3%
      when assessed by Twitch T10. Combining all three expiratory muscle tests reduced
      the number of patients diagnosed as having expiratory muscle weakness to 16.7%.
      CONCLUSION: The use of single tests such as Pimax, Pemax and other available
      individual tests of inspiratory, diaphragm and expiratory muscle strength tends
      to overdiagnose weakness. Combinations of tests increase diagnostic precision
      and, in the population studied, they reduced the diagnosis of inspiratory,
      specific diaphragm and expiratory muscle weakness by 19-56%. Measuring both Pimax
      and Sniff Pnasal resulted in a relative reduction of 19.2% of patients falsely
      diagnosed with inspiratory muscle weakness. The addition of Twitch Pdi to Sniff
      Pdi increased diagnostic precision by a smaller amount (18.9%). Having multiple
      tests of respiratory muscle function available both increases diagnostic
      precision and makes assessment possible in a range of clinical circumstances.

PMID- 17557773
TI  - Hypokalaemic paralysis induced by large amounts of cola consumption.

PMID- 17557774
TI  - Gastrointestinal side effects of mycophenolic acid in renal transplant patients:
      a reappraisal.
AB  - Patient and graft survival following renal transplantation have improved markedly
      over the past decade, meaning that physician attention has turned more towards
      minimizing short- and long-term toxicities associated with immunosuppressive
      regimens. Gastrointestinal (GI) adverse events are common following renal
      transplantation and all immunosuppressive regimens have been associated with such
      events. Mycophenolate mofetil (MMF) or enteric-coated mycophenolate sodium (EC
      MPS) are potential components of immunosuppression regimens, and are associated
      with the most successful outcomes in kidney transplantation. The effects of MMF
      and EC-MPS are likely mediated via the active metabolite mycophenolic acid (MPA).
      The GI events caused by both MMF and EC-MPS may, in part, be related to MPA,
      independent of the formulation or route of administration. MPA may produce GI
      events either through direct action or through the action of it metabolites.
      However, many other factors may cause GI events observed following renal
      transplantation. These include the surgery itself and concurrent diseases such as
      diabetes, and bacterial, viral, fungal and parasitical infections. Additionally,
      numerous concomitant non-immunosuppressive agents, including antibiotics
      hypoglycaemic and proton-pump inhibitors, can be associated with GI events. In a
      recent trial in renal transplant patients with severe diarrhoea, approximately
      50% of patients achieved resolution of diarrhoea through methods other than
      altering their immunosuppressive regimens. Indeed altering of the
      immunosuppressive regimen may lead to the risk of acute rejection. Thus, in order
      to reduce the risk of rejection and subsequent damage to the graft, it is
      important to consider other causes of GI events in renal transplant patients
      before altering immunosuppressive regimens.

PMID- 17557775
TI  - UK Consensus Conference on Early Chronic Kidney Disease--6 and 7 February 2007.

PMID- 17557776
TI  - Cannulating in haemodialysis: rope-ladder or buttonhole technique?
AB  - BACKGROUND: The standard technique for fistula cannulation, the rope-ladder
      technique, is problematic for patients with short fistula lengths and for
      patients in whom the fistula is difficult to cannulate. The buttonhole technique,
      cannulation of exactly the same site, offers the advantage of an easy cannulation
      procedure. However, it can be used only in native fistulas and cannulation is
      preferably executed by a 'single-sticker'. This study was conducted to compare
      these cannulation techniques using objective parameters. METHODS: We introduced
      the buttonhole technique for self-cannulating home haemodialysis patients and
      compared it with baseline data obtained with the rope-ladder technique. Thirty
      three patients with a native arteriovenous fistula were observed prospectively
      during 18 months on the following parameters: cannulating ease, number of bad
      sticks, pain, time of compression after cannula removal, bleeding, infectious
      complications and aneurysm formation. RESULTS: With the buttonhole method,
      cannulating ease improved distinctly, which was especially favourable in patients
      with a short fistula vein. Reported cannulation pain did not change
      significantly. The incidence of bad sticks decreased significantly, as well as
      time of compression after cannula removal, without increased incidence of
      bleeding. Three patients developed a local skin infection of their buttonhole
      during the study, after which the disinfection routine prior to cannulation was
      changed. CONCLUSIONS: Compared with the rope-ladder technique, the buttonhole
      method offers the advantage of an easier cannulation procedure with less bad
      sticks, which has a special benefit for patients with limited access cannulation
      sites or with a fistula which is difficult to cannulate. Prolonged compression
      times or re-bleeding episodes did not occur, but precautions have to be taken in
      order to prevent infectious complications. The buttonhole method can contribute
      considerably to the cannulating ease of self-cannulating patients, thus providing
      a better quality of life.

PMID- 17557777
TI  - N-acetylcysteine reduces urinary albumin excretion following contrast
      administration: evidence of biological effect.
AB  - BACKGROUND: There are conflicting results regarding the effectiveness of N
      acetylcysteine (NAC) in attenuating contrast-induced nephropathy (CIN). NAC
      administration independently reduces serum creatinine, potentially confounding
      studies utilizing creatinine-based endpoints. Albuminuria is a marker of renal
      injury and spot urine albumin: creatinine ratios (ACR) reflect 24-h urine albumin
      excretion. We performed a pre-specified secondary analysis from our published
      negative randomized control trial of NAC for prevention of CIN, to determine if
      NAC administration reduces albuminuria after contrast exposure following cardiac
      catheterization. METHODS: We included study patients who had paired urine
      specimens obtained pre- and post-cardiac catheterization. Baseline
      characteristics were compared using the chi square test or Mann-Whitney U-test,
      as appropriate. Changes in ACR were evaluated using binomial exact test. The
      effect of NAC on post-cardiac catheterization changes in ACR ratio was evaluated
      by ordinal logistic regression. RESULTS: A total of 125 patients met inclusion
      criteria (pre- and post-catheterization urinalysis within 7 days). Baseline
      characteristics neither differ between NAC and placebo groups, nor were they
      different from those who were excluded. Among the patients receiving NAC, 10.7%
      improved their ACR ratio and 7.1% worsened; in contrast, in patients on placebo
      only 4.3% improved, while 21.7% worsened (P=0.015). Change in ACR ratio was not
      associated with change in kidney function as measured by calculated creatinine
      clearance or GFR. CONCLUSIONS: The results of this analysis suggest NAC may
      attenuate contrast-induced glomerular or tubular injury, as defined by albumin
      excretion, and appears to be independent of any effect on creatinine-derived
      measures of kidney function. Larger studies are required to confirm this
      observation.

PMID- 17557778
TI  - High resolution diffusion tensor imaging of axonal damage in focal inflammatory
      and demyelinating lesions in rat spinal cord.
AB  - Inflammation, demyelination, gliosis and axonal degeneration are pathological
      hallmarks of multiple sclerosis (MS) and experimental autoimmune
      encephalomyelitis. Axonal damage is thought to contribute to irreversible damage
      and functional impairment, but is difficult to quantify. Conventional MRI has
      been used to assess the inflammatory and demyelinating aspects of MS lesions, but
      more sensitive and specific methods are needed to identify axonal damage to
      monitor disease progression and to determine efficacy of putative neuroprotective
      agents. We used high resolution diffusion tensor imaging (DTI) and fibre tracking
      to examine the spinal cord in rats with focal dorsal column inflammatory or
      demyelinating lesions to determine whether DTI measures can be used to detect
      pathology at the site of the focal lesion and to measure axonal damage in tracts
      distal to the focal lesion. Distant from the focal lesion, total axon counts,
      degenerating axon counts and SMI-31 staining, but not Luxol fast blue staining,
      were significantly correlated with fractional anisotropy, axial diffusivity and
      radial diffusivity, all of which are derived from the DTI data. These data
      suggest that high resolution DTI may be a more sensitive method than conventional
      imaging for detecting axonal damage at sites distant from inflammation.

PMID- 17557779
TI  - Complexities in the association of human blood brain barrier disruption with
      seizures: importance of patient population and method of disruption.

PMID- 17557780
TI  - Commentary: Life-course and social epidemiology, the biological fig leaf and Bob
      Dylan.

PMID- 17557781
TI  - Commentary: Chasing the elusive null--the story of income inequality and health.

PMID- 17557783
TI  - Pigment spectra and intermolecular interaction potentials in glasses and
      proteins.
AB  - A model is proposed for chromophore optical spectra in solids over a wide range
      of temperatures and pressures. Inhomogeneous band shapes and their pressure
      dependence, as well as baric shift coefficients of spectral lines, selected by
      the frequency, were derived using Lennard-Jones potentials of the ground and
      excited states. Quadratic electron-phonon coupling constants, describing the
      thermal shift and broadening of zero-phonon lines, were also calculated.
      Experimentally, thermal shift and broadening of spectral holes were studied
      between 5 and 40 K for a synthetic pigment, chlorin, embedded in polymer hosts.
      The baric effects on holes were determined by applying hydrostatic He gas
      pressure up to 200 bar, at 6 K. Absorption spectra of pheophytin a, chlorophyll
      a, and beta-carotene in polymers and plant photosystem II CP47 complex were
      measured between 5 (or 77) and 300 K, and subject to Voigtian deconvolution. A
      narrowing of inhomogeneous bandwidth with increasing temperature, predicted on
      the basis of hole behavior, was observed as the shrinking of Gaussian spectral
      component. The Lorentzian broadening was ascribed to optical dephasing up to 300
      K in transitions with weak to moderate linear electron-phonon coupling strength.
      The thermal broadening is purely Gaussian in multiphonon transitions (S(2) band
      of beta-carotene, Soret bands of tetrapyrrolic pigments), and the Lorentz process
      appears to be suppressed, indicating a lack of exponential dephasing. Density,
      polarity, polarizability, compressibility, and other local parameters of the
      pigment binding sites in biologically relevant systems can be deduced from
      spectroscopic data, provided that sufficient background information is available.

PMID- 17557782
TI  - Infrared spectroscopic discrimination between the loop and alpha-helices and
      determination of the loop diffusion kinetics by temperature-jump time-resolved
      infrared spectroscopy for cytochrome c.
AB  - The infrared (IR) absorption of the amide I band for the loop structure may
      overlap with that of the alpha-helices, which can lead to the misassignment of
      the protein secondary structures. A resolution-enhanced Fourier transform
      infrared (FTIR) spectroscopic method and temperature-jump (T-jump) time-resolved
      IR absorbance difference spectra were used to identify one specific loop
      absorption from the helical IR absorption bands of horse heart cytochrome c in
      D2O at a pD around 7.0. This small loop consists of residues 70-85 with Met-80
      binding to the heme Fe(III). The FTIR spectra in amide I' region indicate that
      the loop and the helical absorption bands overlap at 1653 cm(-1) at room
      temperature. Thermal titration of the amide I' intensity at 1653 cm(-1) reveals
      that a transition in loop structural change occurs at lower temperature (Tm=45
      degrees C), well before the global unfolding of the secondary structure (Tm
      approximately 82 degrees C). This loop structural change is assigned as being
      triggered by the Met-80 deligation from the heme Fe(III). T-jump time-resolved IR
      absorbance difference spectra reveal that a T-jump from 25 degrees C to 35
      degrees C breaks the Fe-S bond between the Met-80 and the iron reversibly, which
      leads to a loop (1653 cm(-1), overlap with the helical absorption) to random coil
      (1645 cm(-1)) transition. The observed unfolding rate constant interpreted as the
      intrachain diffusion rate for this 16 residue loop was approximately 3.6x10(6) s(
      1).

PMID- 17557784
TI  - Deciphering protein dynamics from NMR data using explicit structure sampling and
      selection.
AB  - Perhaps one of the most prominent realizations of recent years is the critical
      role that protein dynamics plays in many facets of cellular function. While
      characterization of protein dynamics is fundamental to our understanding of
      protein function, the ability to explicitly detect an ensemble of protein
      conformations from dynamics data is a paramount challenge in structural biology.
      Here, we report a new computational method, Sample and Select, for determining
      the ensemble of protein conformations consistent with NMR dynamics data. This
      method can be generalized and extended to different sources of dynamics data,
      enabling broad applicability in deciphering protein dynamics at different
      timescales. The structural ensemble derived from Sample and Select will provide
      structural and dynamic information that should aid us in understanding and
      manipulating protein function.

PMID- 17557785
TI  - The power of single and multibeam two-photon microscopy for high-resolution and
      high-speed deep tissue and intravital imaging.
AB  - Two-photon microscopy is indispensable for deep tissue and intravital imaging.
      However, current technology based on single-beam point scanning has reached
      sensitivity and speed limits because higher performance requires higher laser
      power leading to sample degradation. We utilize a multifocal scanhead splitting a
      laser beam into a line of 64 foci, allowing sample illumination in real time at
      full laser power. This technology requires charge-coupled device field detection
      in contrast to conventional detection by photomultipliers. A comparison of the
      optical performance of both setups shows functional equivalence in every
      measurable parameter down to penetration depths of 200 microm, where most actual
      experiments are executed. The advantage of photomultiplier detection materializes
      at imaging depths >300 microm because of their better signal/noise ratio, whereas
      only charge-coupled devices allow real-time detection of rapid processes (here
      blood flow). We also find that the point-spread function of both devices strongly
      depends on tissue constitution and penetration depth. However, employment of a
      depth-corrected point-spread function allows three-dimensional deconvolution of
      deep-tissue data up to an image quality resembling surface detection.

PMID- 17557786
TI  - Modeling the two-hybrid detector: experimental bias on protein interaction
      networks.
AB  - This work was done to investigate the two-hybrid experiment for finding protein
      protein interactions to explain the asymmetry found in the experimental data, and
      to help screen the data for high confidence interactions. By looking at the bait
      prey experimental setup the resulting protein interaction network can be examined
      as a directed network (bait --> prey). We have investigated two possible
      scenarios for the asymmetry in the directed network by developing a biochemical
      model for the protein-DNA and protein-protein bindings inside the living yeast.
      One scenario assumes a background activity of bait proteins acting even without
      the prey, the other scenario explores the asymmetry in the chemistry associated
      with the bait being automatically located in the right position on the DNA. We
      conclude that the latter model gives the best description of the observed
      asymmetry.

PMID- 17557787
TI  - B-S transition in short oligonucleotides.
AB  - Stretching experiments with long double-stranded DNA molecules in physiological
      ambient revealed a force-induced transition at a force of 65 pN. During this
      transition between B-DNA and highly overstretched S-DNA the DNA lengthens by a
      factor of 1.7 of its B-form contour length. Here, we report the occurrence of
      this so-called B-S transition in short duplexes consisting of 30 basepairs. We
      employed atomic-force-microscope-based single molecule force spectroscopy to
      explore the unbinding mechanism of two short duplexes containing 30 or 20
      basepairs by pulling at the opposite 5' termini. For a 30-basepair-long DNA
      duplex the B-S transition is expected to cause a length increase of 6.3 nm and
      should therefore be detectable. Indeed 30% of the measured force-extension curves
      exhibit a region of constant force (plateau) at 65 pN, which corresponds to the B
      S transition. The observed plateaus show a length between 3 and 7 nm. This
      plateau length distribution indicates that the dissociation of a 30-basepair
      duplex mainly occurs during the B-S transition. In contrast, the measured force
      extension curves for a 20-basepair DNA duplex exhibited rupture forces below 65
      pN and did not show any evidence of a B-S transition.

PMID- 17557788
TI  - Allosteric transitions in the chaperonin GroEL are captured by a dominant normal
      mode that is most robust to sequence variations.
AB  - The Escherichia coli chaperonin GroEL, which helps proteins to fold, consists of
      two heptameric rings stacked back-to-back. During the reaction cycle GroEL
      undergoes a series of allosteric transitions triggered by ligand (substrate
      protein, ATP, and the cochaperonin GroES) binding. Based on an elastic network
      model of the bullet-shaped double-ring chaperonin GroEL-(ADP)(7)-GroES structure
      (R''T state), we perform a normal mode analysis to explore the energetically
      favorable collective motions encoded in the R''T structure. By comparing each
      normal mode with the observed conformational changes in the R''T --> TR''
      transition, a single dominant normal mode provides a simple description of this
      highly intricate allosteric transition. A detailed analysis of this relatively
      high-frequency mode describes the structural and dynamic changes that underlie
      the positive intra-ring and negative inter-ring cooperativity. The dynamics
      embedded in the dominant mode entails highly concerted structural motions with
      approximate preservation of sevenfold symmetry within each ring and negatively
      correlated ones between the two rings. The dominant normal mode (in comparison
      with the other modes) is robust to parametric perturbations caused by sequence
      variations, which validates its functional importance. Response of the dominant
      mode to local changes that mimic mutations using the structural perturbation
      method technique leads to a wiring diagram that identifies a network of key
      residues that regulate the allosteric transitions. Many of these residues are
      located in intersubunit interfaces, and may therefore play a critical role in
      transmitting allosteric signals between subunits.

PMID- 17557789
TI  - Three-dimensional distribution of cardiac Na+-Ca2+ exchanger and ryanodine
      receptor during development.
AB  - Mechanisms of cardiac excitation-contraction coupling in neonates are still not
      clearly defined. Previous work in neonates shows reverse-mode Na(+)-Ca(2+)
      exchange to be the primary route of Ca(2+) entry during systole and the neonatal
      sarcoplasmic reticulum to have similar capability as that of adult in storing and
      releasing Ca(2+). We investigated Na(+)-Ca(2+) exchanger (NCX) and ryanodine
      receptor (RyR) distribution in developing ventricular myocytes using
      immunofluorescence, confocal microscopy, and digital image analysis. In neonates,
      both NCX and RyR clusters on the surface of the cell displayed a short
      longitudinal periodicity of approximately 0.7 microm. However, by adulthood, both
      proteins were also found in the interior. In the adult, clusters of NCX on the
      surface of the cell retained the approximately 0.7-microm periodicity whereas
      clusters of RyR adopted a longer longitudinal periodicity of approximately 2.0
      microm. This suggests that neonatal myocytes also have a peri-M-line RyR
      distribution that is absent in adult myocytes. NCX and RyR colocalized voxel
      density was maximal in neonates and declined significantly with ontogeny. We
      conclude in newborns, Ca(2+) influx via NCX could potentially activate the dense
      network of peripheral Ca(2+) stores via peripheral couplings, evoking Ca(2+)
      induced Ca(2+) release.

PMID- 17557790
TI  - Flexibility of ras lipid modifications studied by 2H solid-state NMR and
      molecular dynamics simulations.
AB  - Human posttranslationally modified N-ras oncogenes are known to be implicated in
      numerous human cancers. Here, we applied a combination of experimental and
      computational techniques to determine structural and dynamical details of the
      lipid chain modifications of an N-ras heptapeptide in 1,2-dimyristoyl-sn-glycero
      3-phosphocholine (DMPC) membranes. Experimentally, 2H NMR spectroscopy was used
      to study oriented membranes that incorporated ras heptapeptides with two
      covalently attached perdeuterated hexadecyl chains. Atomistic molecular dynamics
      simulations of the same system were carried out over 100 ns including 60 DMPC and
      4 ras molecules. Several structural and dynamical experimental parameters could
      be directly compared to the simulation. Experimental and simulated 2H NMR order
      parameters for the methylene groups of the ras lipid chains exhibited a
      systematic difference attributable to the absence of collective motions in the
      simulation and to geometrical effects. In contrast, experimental 2H NMR spin
      lattice relaxation rates for Zeeman order were well reproduced in the simulation.
      The lack of slower collective motions in the simulation did not appreciably
      influence the relaxation rates at a Larmor frequency of 115.1 MHz. The
      experimental angular dependence of the 2H NMR relaxation rates with respect to
      the external magnetic field was also relatively well simulated. These relaxation
      rates showed a weak angular dependence, suggesting that the lipid modifications
      of ras are very flexible and highly mobile in agreement with the low order
      parameters. To quantify these results, the angular dependence of the 2H
      relaxation rates was calculated by an analytical model considering both molecular
      and collective motions. Peptide dynamics in the membrane could be modeled by an
      anisotropic diffusion tensor with principal values of Dparallel=2.1x10(9) s(-1)
      and Dperpendicular=4.5x10(5) s(-1). A viscoelastic fitting parameter describing
      the membrane elasticity, viscosity, and temperature was found to be relatively
      similar for the ras peptide and the DMPC host matrix. Large motional amplitudes
      and relatively short correlation times facilitate mixing and dispersal with the
      lipid bilayer matrix, with implications for the role of the full-length ras
      protein in signal transduction and oncogenesis.

PMID- 17557791
TI  - Viral DNA packaging studied by fluorescence correlation spectroscopy.
AB  - The DNA packaging machinery of bacteriophage T4 was studied in vitro using
      fluorescence correlation spectroscopy. The ATP-dependent translocation kinetics
      of labeled DNA from the bulk solution, to the phage interior, was measured by
      monitoring the accompanied decrease in DNA diffusibility. It was found that
      multiple short DNA fragments (100 basepairs) can be sequentially packaged by an
      individual phage prohead. Fluorescence resonance energy transfer between green
      fluorescent protein donors within the phage interior and acceptor-labeled DNA was
      used to confirm DNA packaging. Without ATP, no packaging was observed, and there
      was no evidence of substrate association with the prohead.

PMID- 17557792
TI  - A monomeric membrane peptide that lives in three worlds: in solution, attached
      to, and inserted across lipid bilayers.
AB  - The membrane peptide pH (low) insertion peptide (pHLIP) lives in three worlds,
      being soluble in aqueous solution at pH 7.4, binding to the surface of lipid
      bilayers, and inserting as a transbilayer helix at low pH. With low pH driving
      the process, pHLIP can translocate cargo molecules attached to its C-terminus via
      a disulfide and release them in the cytoplasm of a cell. Here we examine a key
      aspect of the mechanism, showing that pHLIP is monomeric in each of its three
      major states: soluble in water near neutral pH (state I), bound to the surface of
      a membrane near neutral pH (state II), and inserted across the membrane as an
      alpha-helix at low pH (state III). The peptide does not induce fusion or membrane
      leakage. The unique properties of pHLIP made it attractive for the biophysical
      investigation of membrane protein folding in vitro and for the development of a
      novel class of delivery peptides for the transport of therapeutic and diagnostic
      agents to acidic tissue sites associated with various pathological processes in
      vivo.

PMID- 17557793
TI  - Rows of ATP synthase dimers in native mitochondrial inner membranes.
AB  - The ATP synthase is a nanometric rotary machine that uses a transmembrane
      electrochemical gradient to form ATP. The structures of most components of the
      ATP synthase are known, and their organization has been elucidated. However, the
      supramolecular assembly of ATP synthases in biological membranes remains unknown.
      Here we show with submolecular resolution the organization of ATP synthases in
      the yeast mitochondrial inner membranes. The atomic force microscopy images we
      have obtained show how these molecules form dimers with characteristic 15 nm
      distance between the axes of their rotors through stereospecific interactions of
      the membrane embedded portions of their stators. A different interaction surface
      is responsible for the formation of rows of dimers. Such an organization
      elucidates the role of the ATP synthase in mitochondrial morphology. Some dimers
      have a different morphology with 10 nm stalk-to-stalk distance, in line with ATP
      synthases that are accessible to IF1 inhibition. Rotation torque compensation
      within ATP synthase dimers stabilizes the ATP synthase structure, in particular
      the stator-rotor interaction.

PMID- 17557794
TI  - Phospholipase D activity is regulated by product segregation and the structure
      formation of phosphatidic acid within model membranes.
AB  - Phospholipase D from Streptomyces chromofuscus (scPLD) hydrolyzes
      phosphatidylcholines (PC) to produce choline and phosphatidic acid (PA), a lipid
      messenger molecule within biological membranes. To scrutinize the influence of
      membrane structure on scPLD activity, three different substrate-containing
      monolayers are used as model systems: pure dipalmitoylphosphatidylcholine (DPPC)
      as well as equimolar mixtures of DPPC/n-hexadecanol (C(16)OH) and
      DPPC/dipalmitoylglycerol (DPG). The activity of scPLD toward these monolayers is
      tested by infrared reflection-absorption spectroscopy and exhibits different
      dependencies on surface pressure. For pure DPPC, the catalytic turnover
      drastically drops above 20 mN/m. On addition of C(16)OH, this strong decrease
      starts at 5 mN/m. For the DPPC/DPG system, the reaction yield linearly decreases
      between 5 and 25 mN/m. The difference in scPLD activity is correlated to the
      phase state of the monolayers as examined by x-ray diffraction, Brewster angle
      microscopy, and atomic force microscopy. Because the additives C(16)OH and DPG
      mediate the miscibility of PC and PA, only a basal activity of scPLD is observed
      toward the mixed systems at higher surface pressures. At pure DPPC monolayers,
      scPLD is activated after the segregation of initially formed PA. Furthermore,
      scPLD is inhibited when the lipids in the PA-rich domains adopt an upright
      orientation. This phenomenon offers a self-regulating mechanism for the
      concentration of the second messenger PA within biological membranes.

PMID- 17557795
TI  - Collagen organization in canine myxomatous mitral valve disease: an x-ray
      diffraction study.
AB  - Collagen fibrils, a major component of mitral valve leaflets, play an important
      role in defining shape and providing mechanical strength and flexibility.
      Histopathological studies show that collagen fibrils undergo dramatic changes in
      the course of myxomatous mitral valve disease in both dogs and humans. However,
      little is known about the detailed organization of collagen in this disease. This
      study was designed to analyze and compare collagen fibril organization in healthy
      and lesional areas of myxomatous mitral valves of dogs, using synchrotron small
      angle x-ray diffraction. The orientation, density, and alignment of collagen
      fibrils were mapped across six different valves. The findings reveal a preferred
      collagen alignment in the main body of the leaflets between two commissures.
      Qualitative and quantitative analysis of the data showed significant differences
      between affected and lesion-free areas in terms of collagen content, fibril
      alignment, and total tissue volume. Regression analysis of the amount of collagen
      compared to the total tissue content at each point revealed a significant
      relationship between these two parameters in lesion-free but not in affected
      areas. This is the first time this technique has been used to map collagen
      fibrils in cardiac tissue; the findings have important applications to human
      cardiology.

PMID- 17557796
TI  - Occurrence and clinical correlates of REM sleep behaviour disorder in patients
      with Parkinson's disease over time.
AB  - OBJECTIVE: To examine the occurrence and clinical and demographic correlates of
      REM sleep behaviour disorder (RBD) in patients with Parkinson's disease (PD) in a
      community-based cohort over 8 years. METHODS: 231 patients with PD were included
      in a population-based prevalence study in 1993. Patients were then followed
      prospectively and reexamined after 4 and 8 years. Semi-structured interviews for
      information on clinical and demographic data were applied at all study visits.
      Standardised rating scales of parkinsonism, depression and cognitive impairment
      were used. The diagnosis of probable RBD (pRBD) was based on a sleep
      questionnaire. Proportional-odds ordinal logistic regression models for clustered
      data were used to study the relationship between pRBD and various demographic and
      clinical variables. RESULTS: 231 patients were evaluated for RBD in 1993 and,
      after 4 and 8 years, 142 and 89 patients, respectively, were available for re
      evaluation. The frequency of pRBD varied from 14.6% to 27% during the study
      period. Probable RBD was related to male gender, higher dopaminergic treatment
      and less severe parkinsonism. CONCLUSION: We found that the frequency of pRBD
      varied over time and that it is associated with male gender, less parkinsonism
      and higher levodopa equivalent dose. Our findings indicate that dopaminergic
      therapy may contribute to the expression of RBD and that RBD is symptomatic in
      earlier stages of PD.

PMID- 17557797
TI  - Odour identification test and its relation to cardiac 123I
      metaiodobenzylguanidine in patients with drug induced parkinsonism.
AB  - We investigated olfactory function and its relation to cardiac 123I
      metaiodobenzylguanidine (MIBG) uptake in 15 patients with drug induced
      parkinsonism (DIP). The mean Cross Cultural Smell Identification (CCSI) score was
      significantly greater in patients with DIP than in those with Parkinson's disease
      (PD: 6.9 (1.6) vs 4.4 (2.2); p<0.001); however, the mean CCSI score in patients
      with DIP was not significantly different from controls. One patient with DIP,
      whose CCSI score was significantly reduced, also exhibited decreased cardiac MIBG
      uptake. DIP patients with CCSI scores within the normal range had normal cardiac
      MIBG uptake. Our study suggests that an olfactory function test may be a useful
      tool for detecting DIP unrelated to PD and for identifying patients with DIP who
      have subclinical PD.

PMID- 17557798
TI  - Relation between cognitive dysfunction and reduced vital capacity in amyotrophic
      lateral sclerosis.
AB  - BACKGROUND: Many patients with amyotrophic lateral sclerosis (ALS) with cognitive
      impairment have fronto-temporal dysfunction. Whereas in some patients with ALS
      the fronto-temporal dysfunction is undoubtedly due to the degenerative process
      associated with the disease, in others dysfunction cannot be accounted for by an
      irreversible degenerative process alone, as it also appears to involve a
      reversible process. We hypothesised that reduced vital capacity can be a key
      contributor to the fronto-temporal dysfunction observed in patients with ALS.
      OBJECTIVE: To investigate the association between fronto-temporal dysfunction and
      reduced vital capacity in ALS. METHODS: 16 consecutive patients who conformed to
      a diagnosis of definite or probable ALS (El escorial criteria) were grouped by
      vital capacity, and their clinical characteristics and cognitive functions,
      including disease duration, attention, executive function and memory, were
      measured. RESULTS: Patients with a reduced vital capacity performed significantly
      poorer in memory retention (p = 0.028), retrieval efficacy (p = 0.003), spoken
      verbal fluency (p = 0.03) and spoken verbal fluency indexes (p = 0.016) than
      those with a normal vital capacity. CONCLUSION: The fronto-temporal dysfunction
      in ALS might be attributable to potentially reversible secondary effects
      associated with reduced vital capacity, as well as to the primary degenerative
      process.

PMID- 17557800
TI  - Effects of cardiogenic edema fluid on ion and fluid transport in the adult lung.
AB  - We have previously shown that cardiogenic pulmonary edema fluid (EF) increases
      Na(+) and fluid transport by fetal distal lung epithelia (FDLE) (Rafii B, Gillie
      DJ, Sulowski C, Hannam V, Cheung T, Otulakowski G, Barker PM and O'Brodovich H. J
      Physiol 544: 537-548, 2002). We now report the effect of EF on Na(+) and fluid
      transport by the adult lung. We first studied primary cultures of adult type II
      (ATII) epithelium and found that overnight exposure to EF increased Na(+)
      transport, and this effect was mainly due to factors other than catecholamines.
      Plasma did not stimulate Na(+) transport in ATII. Purification of EF demonstrated
      that at least some agent(s) responsible for the amiloride-insensitive component
      resided within the globulin fraction. ATII exposed to globulins demonstrated a
      conversion of amiloride-sensitive short-circuit current (I(sc)) to amiloride
      insensitive I(sc) with no increase in total I(sc). Patch-clamp studies showed
      that ATII exposed to EF for 18 h had increased the number of highly selective
      Na(+) channels in their apical membrane. In situ acute exposure to EF increased
      the open probability of Na(+)-permeant ion channels in ATII within rat lung
      slices. EF did increase, by amiloride-sensitive pathways, the alveolar fluid
      clearance from the lungs of adult rats. We conclude that cardiogenic EF increases
      Na(+) transport by adult lung epithelia in primary cell culture, in situ and in
      vivo.

PMID- 17557799
TI  - PGE(2) inhibition of TGF-beta1-induced myofibroblast differentiation is Smad
      independent but involves cell shape and adhesion-dependent signaling.
AB  - Myofibroblasts are pathogenic in pulmonary fibrotic disease due to their
      exuberant production of matrix rich in collagen that interferes with gas exchange
      and the ability of these cells to contract and distort the alveolar space.
      Transforming growth factor-beta1 (TGF-beta1) is a well-known inducer of
      myofibroblast differentiation. TGF-beta1-induced transformation of fibroblasts to
      apoptosis-resistant myofibroblasts is adhesion-dependent and focal adhesion
      kinase (FAK)-mediated. Prostaglandin E(2) (PGE(2)) inhibits this differentiation
      via E prostanoid receptor 2 (EP2) signaling and cAMP elevation, but whether
      PGE(2) does so by interfering with TGF-beta1 signaling is unknown. Thus we
      examined the effects of PGE(2) in the presence and absence of TGF-beta1
      stimulation on candidate signaling pathways in human lung fibroblasts. We now
      demonstrate that PGE(2) does not interfere with TGF-beta1-induced Smad
      phosphorylation or its translocation to the nucleus. Rather, PGE(2) has dramatic
      effects on cell shape and cytoskeletal architecture and disrupts the formation of
      appropriate focal adhesions. PGE(2) treatment diminishes TGF-beta1-induced
      phosphorylation of paxillin, STAT-3, and FAK and, in turn, limits activation of
      the protein kinase B (PKB/Akt) pathway. These alterations do not, however, result
      in increased apoptosis within the first 24 h of treatment. Interestingly, the
      effects of PGE(2) stimulation alone do not always mirror the effects of PGE(2) in
      the presence of TGF-beta1, indicating that the context for EP2 signaling is
      different in the presence of TGF-beta1. Taken together, our results demonstrate
      that PGE(2) has the potential to limit TGF-beta1-induced myofibroblast
      differentiation via adhesion-dependent, but Smad-independent, pathways.

PMID- 17557801
TI  - Adrenomedullin ameliorates lipopolysaccharide-induced acute lung injury in rats.
AB  - Adrenomedullin (AM), an endogenous peptide, has been shown to have a variety of
      protective effects on the cardiovascular system. However, the effect of AM on
      acute lung injury remains unknown. Accordingly, we investigated whether AM
      infusion ameliorates lipopolysaccharide (LPS)-induced acute lung injury in rats.
      Rats were randomized to receive continuous intravenous infusion of AM (0.1 microg
      x kg(-1) x min(-1)) or vehicle through a microosmotic pump. The animals were
      intratracheally injected with either LPS (1 mg/kg) or saline. At 6 and 18 h after
      intratracheal instillation, we performed histological examination and
      bronchoalveolar lavage and assessed the lung wet/dry weight ratio as an index of
      acute lung injury. Then we measured the numbers of total cells and neutrophils
      and the levels of tumor necrosis factor (TNF)-alpha and cytokine-induced
      neutrophil chemoattractant (CINC) in bronchoalveolar lavage fluid (BALF). In
      addition, we evaluated BALF total protein and albumin levels as indexes of lung
      permeability. LPS instillation caused severe acute lung injury, as indicated by
      the histological findings and the lung wet/dry weight ratio. However, AM infusion
      attenuated these LPS-induced abnormalities. AM decreased the numbers of total
      cells and neutrophils and the levels of TNF-alpha and CINC in BALF. AM also
      reduced BALF total protein and albumin levels. In addition, AM significantly
      suppressed apoptosis of alveolar wall cells as indicated by cleaved caspase-3
      staining. In conclusion, continuous infusion of AM ameliorated LPS-induced acute
      lung injury in rats. This beneficial effect of AM on acute lung injury may be
      mediated by inhibition of inflammation, hyperpermeability, and alveolar wall cell
      apoptosis.

PMID- 17557803
TI  - Heterogeneity of transcription factor expression and regulation in human airway
      epithelial and smooth muscle cells.
AB  - Transcription factors represent a major mechanism by which cells establish basal
      and conditional expression of proteins, the latter potentially being adaptive or
      maladaptive in disease. The complement of transcription factors in two major
      structural cells of the lung relevant to asthma, airway epithelial and smooth
      muscle cells, is not known. A plate-based platform using nuclear extracts from
      these cells was used to assess potential expression by binding to oligonucleotide
      consensus sequences representing >300 transcription factors. Four conditions were
      studied: basal, beta-agonist exposure, culture under proasthmatic conditions (IL
      13, IL-4, TGF-beta, and leukotriene D(4)), and the dual setting of beta-agonist
      with proasthmatic culture. Airway epithelial cells expressed 70 transcription
      factors, whereas airway smooth muscle expressed 110. High levels of multiple
      transcription factors not previously recognized as being expressed in these cells
      were identified. Moreover, expression/ binding patterns under these conditions
      revealed extreme discordance in the direction and magnitude of change between the
      cell types. Singular (one cell type displayed regulation) and antithetic (both
      cell types underwent expression changes but in opposite directions) regulation
      dominated these patterns, with concomitant regulation in both cell types being
      rare (<10%). beta-Agonist evoked up- and downregulation of transcription factors,
      which was highly influenced by the proasthmatic condition, with little overlap of
      factors regulated by beta-agonists under both conditions. Together, these results
      reveal complex, cell type-dependent networks of transcription factors in human
      airway epithelium and smooth muscle that are dynamically regulated in unique ways
      by beta-agonists and inflammation. These factors may represent additional
      components in asthma pathophysiology or potential new drug targets.

PMID- 17557802
TI  - MAPK and heat shock protein 27 activation are associated with respiratory
      syncytial virus induction of human bronchial epithelial monolayer disruption.
AB  - Respiratory syncytial virus (RSV) is the major cause of bronchiolitis in infants,
      and a common feature of RSV infections is increased lung permeability. The
      accumulation of fluid in the infected lungs is caused by changes in the
      endothelial and epithelial membrane integrity. However, the exact mechanisms of
      viral-induced fluid extravasation remain unclear. Here, we report that infection
      of human epithelial cells with RSV results in significant epithelial membrane
      barrier disruption as assessed by a decrease in transepithelial electrical
      resistance (TEpR). This decrease in TEpR, which indicates changes in paracellular
      permeability, was mediated by marked cellular cytoskeletal rearrangement.
      Importantly, the decrease in TEpR was attenuated by using p38 MAPK inhibitors (SB
      203580) but was partially affected by JNK inhibitor SP-600125. Interestingly,
      treatment of A549 cells with MEK1/2 inhibitor (U-0126) led to a decrease in TEpR
      in the absence of RSV infection. The changes in TEpR were concomitant with an
      increase in heat shock protein 27 (Hsp27) phosphorylation and with actin
      microfilament rearrangement. Thus our data suggest that p38 MAPK and Hsp27 are
      required for RSV induction of human epithelial membrane permeability.

PMID- 17557804
TI  - Membrane type 1 matrix metalloproteinase is necessary for distal airway
      epithelial repair and keratinocyte growth factor receptor expression after acute
      injury.
AB  - Membrane type 1 matrix metalloproteinase (MT1-MMP) is a protease produced by
      airway epithelial cells in various diseases. Since other MMPs are involved in
      bronchial epithelial repair, we investigated the role of MT1-MMP in naphthalene
      induced small airway injury and repair in wild-type (WT) and MT1-MMP-knockout
      (KO) mice. The degree of injury was similar in both strains, but the MT1-MMP KO
      mice were unable to reconstitute a normal, fully differentiated airway epithelium
      28 days after injury. MT1-MMP was required for the proliferative response in
      distal airway epithelial cells, resulting in decreased cell density and airway
      epithelial cell differentiation in MT1-MMP KO mice. Surprisingly, EGF-mediated
      signaling was unaltered in MT1-MMP KO mice and therefore unrelated to the
      proliferative response. However, keratinocyte growth factor receptor (KGFR)
      expression was significantly upregulated before the proliferative response and
      markedly less evident in the distal airway epithelium of MT1-MMP KO mice. These
      results indicate MT1-MMP is involved in KGFR expression and epithelial cell
      proliferation after acute airway injury.

PMID- 17557805
TI  - Separating the roles of acropetal and basipetal auxin transport on gravitropism
      with mutations in two Arabidopsis multidrug resistance-like ABC transporter
      genes.
AB  - Two Arabidopsis thaliana ABC transporter genes linked to auxin transport by
      various previous results were studied in a reverse-genetic fashion. Mutations in
      Multidrug Resistance-Like1 (MDR1) reduced acropetal auxin transport in roots by
      80% without affecting basipetal transport. Conversely, mutations in MDR4 blocked
      50% of basipetal transport without affecting acropetal transport. Developmental
      and auxin distribution phenotypes associated with these altered auxin flows were
      studied with a high-resolution morphometric system and confocal microscopy,
      respectively. Vertically grown mdr1 roots produced positive and negative
      curvatures threefold greater than the wild type, possibly due to abnormal auxin
      distribution observed in the elongation zone. However, upon 90 degrees
      reorientation, mdr1 gravitropism was inseparable from the wild type. Thus,
      acropetal auxin transport maintains straight growth but contributes surprisingly
      little to gravitropism. Conversely, vertically maintained mdr4 roots grew as
      straight as the wild type, but their gravitropism was enhanced. Upon
      reorientation, curvature in this mutant developed faster, was distributed more
      basally, and produced a greater total angle than the wild type. An amplified
      auxin asymmetry may explain the mdr4 hypertropism. Double mutant analysis
      indicated that the two auxin transport streams are more independent than
      interdependent. The hypothesis that flavanols regulate MDR-dependent auxin
      transport was supported by the epistatic relationship of mdr4 to the tt4
      phenylpropanoid pathway mutation.

PMID- 17557806
TI  - Structural evidence for the evolution of xyloglucanase activity from xyloglucan
      endo-transglycosylases: biological implications for cell wall metabolism.
AB  - High-resolution, three-dimensional structures of the archetypal glycoside
      hydrolase family 16 (GH16) endo-xyloglucanases Tm-NXG1 and Tm-NXG2 from
      nasturtium (Tropaeolum majus) have been solved by x-ray crystallography. Key
      structural features that modulate the relative rates of substrate hydrolysis to
      transglycosylation in the GH16 xyloglucan-active enzymes were identified by
      structure-function studies of the recombinantly expressed enzymes in comparison
      with data for the strict xyloglucan endo-transglycosylase Ptt-XET16-34 from
      hybrid aspen (Populus tremula x Populus tremuloides). Production of the loop
      deletion variant Tm-NXG1-DeltaYNIIG yielded an enzyme that was structurally
      similar to Ptt-XET16-34 and had a greatly increased transglycosylation:hydrolysis
      ratio. Comprehensive bioinformatic analyses of XTH gene products, together with
      detailed kinetic data, strongly suggest that xyloglucanase activity has evolved
      as a gain of function in an ancestral GH16 XET to meet specific biological
      requirements during seed germination, fruit ripening, and rapid wall expansion.

PMID- 17557807
TI  - Mutations in Arabidopsis multidrug resistance-like ABC transporters separate the
      roles of acropetal and basipetal auxin transport in lateral root development.
AB  - Auxin affects the shape of root systems by influencing elongation and branching.
      Because multidrug resistance (MDR)-like ABC transporters participate in auxin
      transport, they may be expected to contribute to root system development. This
      reverse genetic study of Arabidopsis thaliana roots shows that MDR4-mediated
      basipetal auxin transport did not affect root elongation or branching. However,
      impaired acropetal auxin transport due to mutation of the MDR1 gene caused 21% of
      nascent lateral roots to arrest their growth and the remainder to elongate 50%
      more slowly than the wild type. Reporter gene analyses indicated a severe auxin
      deficit in the apex of mdr1 but not mdr4 lateral roots. The mdr1 deficit was
      explained by 40% less acropetal auxin transport within the mdr1 lateral roots.
      The slow elongation of mdr1 lateral roots was rescued by auxin and phenocopied in
      the wild type by an inhibitor of polar auxin transport. Confocal microscopy
      analysis of a functional green fluorescent protein-MDR1 translational fusion
      showed the protein to be auxin inducible and present in the tissues responsible
      for acropetal transport in the primary root. The protein also accumulated in
      lateral root primordia and later in the tissues responsible for acropetal
      transport within the lateral root, fully supporting the conclusion that auxin
      levels established by MDR1-dependent acropetal transport control lateral root
      growth rate to influence root system architecture.

PMID- 17557808
TI  - A heteromeric plastidic pyruvate kinase complex involved in seed oil biosynthesis
      in Arabidopsis.
AB  - Glycolysis is a ubiquitous pathway thought to be essential for the production of
      oil in developing seeds of Arabidopsis thaliana and oil crops. Compartmentation
      of primary metabolism in developing embryos poses a significant challenge for
      testing this hypothesis and for the engineering of seed biomass production. It
      also raises the question whether there is a preferred route of carbon from
      imported photosynthate to seed oil in the embryo. Plastidic pyruvate kinase
      catalyzes a highly regulated, ATP-producing reaction of glycolysis. The
      Arabidopsis genome encodes 14 putative isoforms of pyruvate kinases. Three genes
      encode subunits alpha, beta(1), and beta(2) of plastidic pyruvate kinase. The
      plastid enzyme prevalent in developing seeds likely has a subunit composition of
      4alpha4beta(1), is most active at pH 8.0, and is inhibited by Glu. Disruption of
      the gene encoding the beta(1) subunit causes a reduction in plastidic pyruvate
      kinase activity and 60% reduction in seed oil content. The seed oil phenotype is
      fully restored by expression of the beta(1) subunit-encoding cDNA and partially
      by the beta(2) subunit-encoding cDNA. Therefore, the identified pyruvate kinase
      catalyzes a crucial step in the conversion of photosynthate into oil, suggesting
      a preferred plastid route from its substrate phosphoenolpyruvate to fatty acids.

PMID- 17557809
TI  - Rational conversion of substrate and product specificity in a Salvia monoterpene
      synthase: structural insights into the evolution of terpene synthase function.
AB  - Terpene synthases are responsible for the biosynthesis of the complex chemical
      defense arsenal of plants and microorganisms. How do these enzymes, which all
      appear to share a common terpene synthase fold, specify the many different
      products made almost entirely from one of only three substrates? Elucidation of
      the structure of 1,8-cineole synthase from Salvia fruticosa (Sf-CinS1) combined
      with analysis of functional and phylogenetic relationships of enzymes within
      Salvia species identified active-site residues responsible for product
      specificity. Thus, Sf-CinS1 was successfully converted to a sabinene synthase
      with a minimum number of rationally predicted substitutions, while identification
      of the Asn side chain essential for water activation introduced 1,8-cineole and
      alpha-terpineol activity to Salvia pomifera sabinene synthase. A major
      contribution to product specificity in Sf-CinS1 appears to come from a local
      deformation within one of the helices forming the active site. This deformation
      is observed in all other mono- or sesquiterpene structures available, pointing to
      a conserved mechanism. Moreover, a single amino acid substitution enlarged the
      active-site cavity enough to accommodate the larger farnesyl pyrophosphate
      substrate and led to the efficient synthesis of sesquiterpenes, while alternate
      single substitutions of this critical amino acid yielded five additional terpene
      synthases.

PMID- 17557810
TI  - Arabidopsis JAGGED LATERAL ORGANS is expressed in boundaries and coordinates KNOX
      and PIN activity.
AB  - Plant lateral organs are initiated as small protrusions on the flanks of shoot
      apical meristems. Organ primordia are separated from the remainder of the
      meristem by distinct cell types that create a morphological boundary. The
      Arabidopsis thaliana gain-of-function mutant jagged lateral organs-D (jlo-D)
      develops strongly lobed leaves, indicative of KNOX gene misexpression, and the
      shoot apical meristem arrests organ initiation prematurely, terminating in a pin
      like structure. The JLO gene, a member of the LATERAL ORGAN BOUNDARY DOMAIN gene
      family, is expressed in boundaries between meristems and organ primordia and
      during embryogenesis. Inducible JLO misexpression activates expression of the
      KNOX genes SHOOT MERISTEMLESS and KNAT1 in leaves and downregulates the
      expression of PIN auxin export facilitators. Consequently, bulk auxin transport
      through the inflorescence stem is drastically reduced. During embryogenesis, JLO
      is required for the initiation of cotyledons and development beyond the globular
      stage. Converting JLO into a transcriptional repressor causes organ fusions,
      showing that during postembryonic development, JLO function is required to
      maintain the integrity of boundaries between cell groups with indeterminate or
      determinate fates.

PMID- 17557811
TI  - The triploid endosperm genome of Arabidopsis adopts a peculiar, parental-dosage
      dependent chromatin organization.
AB  - The endosperm is a seed tissue unique to flowering plants. Due to its central
      role in nourishing and protecting the embryo, endosperm development is subject to
      parental conflicts and adaptive processes, which led to the evolution of parent
      of-origin-dependent gene regulation. The role of higher-order chromatin
      organization in regulating the endosperm genome was long ignored due to technical
      hindrance. We developed a combination of approaches to analyze nuclear structure
      and chromatin organization in Arabidopsis thaliana endosperm. Endosperm nuclei
      showed a less condensed chromatin than other types of nuclei and a peculiar
      heterochromatin organization, with smaller chromocenters and additional
      heterochromatic foci interspersed in euchromatin. This is accompanied by a
      redistribution of the heterochromatin mark H3K9me1 from chromocenters toward
      euchromatin and interspersed heterochromatin. Thus, endosperm nuclei have a
      specific nuclear architecture and organization, which we interpret as a relaxed
      chromocenter-loop model. The analysis of endosperm with altered parental genome
      dosage indicated that the additional heterochromatin may be predominantly of
      maternal origin, suggesting differential regulation of maternal and paternal
      genomes, possibly linked to genome dosage regulation.

PMID- 17557812
TI  - Relative abundance of the human mitochondrial transcription system and distinct
      roles for h-mtTFB1 and h-mtTFB2 in mitochondrial biogenesis and gene expression.
AB  - Human mitochondrial transcription requires the bacteriophage-related RNA
      polymerase, POLRMT, the mtDNA-binding protein, h-mtTFA/TFAM, and two
      transcription factors/rRNA methyltransferases, h-mtTFB1 and h-mtTFB2. Here, we
      determined the steady-state levels of these core transcription components and
      examined the consequences of purposeful elevation of h-mtTFB1 or h-mtTFB2 in HeLa
      cells. On a per molecule basis, we find an approximately 6-fold excess of POLRMT
      to mtDNA and approximately 3-fold more h-mtTFB2 than h-mtTFB1. We also estimate h
      mtTFA at approximately 50 molecules/mtDNA, a ratio predicted to support robust
      transcription, but not to coat mtDNA. Consistent with a role for h-mtTFB2 in
      transcription and transcription-primed replication, increased mitochondrial DNA
      and transcripts result from its over-expression. This is accompanied by increased
      translation rates of most, but not all mtDNA-encoded proteins. Over-expression of
      h-mtTFB1 did not significantly influence these parameters, but did result in
      increased mitochondrial biogenesis. Furthermore, h-mtTFB1 mRNA and protein are
      elevated in response to h-mtTFB2 over-expression, suggesting the existence of a
      retrograde signal to the nucleus to coordinately regulate expression of these
      related factors. Altogether, our results provide a framework for understanding
      the regulation of human mitochondrial transcription in vivo and define distinct
      roles for h-mtTFB1 and h-mtTFB2 in mitochondrial biogenesis and gene expression
      that together likely fine-tune mitochondrial function.

PMID- 17557813
TI  - Synthesis and investigation of deoxyribonucleic acid/locked nucleic acid chimeric
      molecular beacons.
AB  - To take full advantage of locked nucleic acid (LNA) based molecular beacons (LNA
      MBs) for a variety of applications including analysis of complex samples and
      intracellular monitoring, we have systematically synthesized a series of DNA/LNA
      chimeric MBs and studied the effect of DNA/LNA ratio in MBs on their
      thermodynamics, hybridization kinetics, protein binding affinity and enzymatic
      resistance. It was found that the LNA bases in a MB stem sequence had a
      significant effect on the stability of the hair-pin structure. The hybridization
      rates of LNA-MBs were significantly improved by lowering the DNA/LNA ratio in the
      probe, and most significantly, by having a shared-stem design for the LNA-MB to
      prevent sticky-end pairing. It was found that only MB sequences with DNA/LNA
      alternating bases or all LNA bases were able to resist nonspecific protein
      binding and DNase I digestion. Additional results showed that a sequence
      consisting of a DNA stretch less than three bases between LNA bases was able to
      block RNase H function. This study suggested that a shared-stem MB with a 4 base
      pair stem and alternating DNA/LNA bases is desirable for intracellular
      applications as it ensures reasonable hybridization rates, reduces protein
      binding and resists nuclease degradation for both target and probes. These
      findings have implications on the design of LNA molecular probes for
      intracellular monitoring application, disease diagnosis and basic biological
      studies.

PMID- 17557814
TI  - Copper induction of lactate oxidase of Lactococcus lactis: a novel metal stress
      response.
AB  - Lactococcus lactis IL1403, a lactic acid bacterium widely used for food
      fermentation, is often exposed to stress conditions. One such condition is
      exposure to copper, such as in cheese making in copper vats. Copper is an
      essential micronutrient in prokaryotes and eukaryotes but can be toxic if in
      excess. Thus, copper homeostatic mechanisms, consisting chiefly of copper
      transporters and their regulators, have evolved in all organisms to control
      cytoplasmic copper levels. Using proteomics to identify novel proteins involved
      in the response of L. lactis IL1403 to copper, cells were exposed to 200 muM
      copper sulfate for 45 min, followed by resolution of the cytoplasmic fraction by
      two-dimensional gel electrophoresis. One protein strongly induced by copper was
      LctO, which was shown to be a NAD-independent lactate oxidase. It catalyzed the
      conversion of lactate to pyruvate in vivo and in vitro. Copper, cadmium, and
      silver induced LctO, as shown by real-time quantitative PCR. A copper-regulatory
      element was identified in the 5' region of the lctO gene and shown to interact
      with the CopR regulator, encoded by the unlinked copRZA operon. Induction of LctO
      by copper represents a novel copper stress response, and we suggest that it
      serves in the scavenging of molecular oxygen.

PMID- 17557815
TI  - A genomic view of sugar transport in Mycobacterium smegmatis and Mycobacterium
      tuberculosis.
AB  - We present a comprehensive analysis of carbohydrate uptake systems of the soil
      bacterium Mycobacterium smegmatis and the human pathogen Mycobacterium
      tuberculosis. Our results show that M. smegmatis has 28 putative carbohydrate
      transporters. The majority of sugar transport systems (19/28) in M. smegmatis
      belong to the ATP-binding cassette (ABC) transporter family. In contrast to
      previous reports, we identified genes encoding all components of the
      phosphotransferase system (PTS), including permeases for fructose, glucose, and
      dihydroxyacetone, in M. smegmatis. It is anticipated that the PTS of M. smegmatis
      plays an important role in the global control of carbon metabolism similar to
      those of other bacteria. M. smegmatis further possesses one putative glycerol
      facilitator of the major intrinsic protein family, four sugar permeases of the
      major facilitator superfamily, one of which was assigned as a glucose
      transporter, and one galactose permease of the sodium solute superfamily. Our
      predictions were validated by gene expression, growth, and sugar transport
      analyses. Strikingly, we detected only five sugar permeases in the slow-growing
      species M. tuberculosis, two of which occur in M. smegmatis. Genes for a PTS are
      missing in M. tuberculosis. Our analysis thus brings the diversity of
      carbohydrate uptake systems of fast- and a slow-growing mycobacteria to light,
      which reflects the lifestyles of M. smegmatis and M. tuberculosis in their
      natural habitats, the soil and the human body, respectively.

PMID- 17557816
TI  - Mutations in the tryptophan operon allow PurF-independent thiamine synthesis by
      altering flux in vivo.
AB  - Phosphoribosyl amine (PRA) is an intermediate in purine biosynthesis and also
      required for thiamine biosynthesis in Salmonella enterica. PRA is normally
      synthesized by phosphoribosyl pyrophosphate amidotransferase, a high-turnover
      enzyme of the purine biosynthetic pathway encoded by purF. However, PurF
      independent PRA synthesis has been observed in strains having different genetic
      backgrounds and growing under diverse conditions. Genetic analysis has shown that
      the anthranilate synthase-phosphoribosyltransferase (AS-PRT) enzyme complex,
      involved in the synthesis of tryptophan, can play a role in the synthesis of PRA.
      This work describes the in vitro synthesis of PRA in the presence of the purified
      components of the AS-PRT complex. Results from in vitro assays and in vivo
      studies indicate that the cellular accumulation of phosphoribosyl anthranilate
      can result in nonenzymatic PRA formation sufficient for thiamine synthesis. These
      studies have uncovered a mechanism used by cells to redistribute metabolites to
      ensure thiamine synthesis and may define a general paradigm of metabolic
      robustness.

PMID- 17557817
TI  - ESAT-6 from Mycobacterium tuberculosis dissociates from its putative chaperone
      CFP-10 under acidic conditions and exhibits membrane-lysing activity.
AB  - The 6-kDa early secreted antigenic target ESAT-6 and the 10-kDa culture filtrate
      protein CFP-10 of Mycobacterium tuberculosis are secreted by the ESX-1 system
      into the host cell and thereby contribute to pathogenicity. Although different
      studies performed at the organismal and cellular levels have helped to explain
      ESX-1-associated phenomena, not much is known about how ESAT-6 and CFP-10
      contribute to pathogenesis at the molecular level. In this study we describe the
      interaction of both proteins with lipid bilayers, using biologically relevant
      liposomal preparations containing dimyristoylphosphatidylcholine (DMPC),
      dimyristoylphosphatidylglycerol, and cholesterol. Using flotation gradient
      centrifugation, we demonstrate that ESAT-6 showed strong association with
      liposomes, and in particular with preparations containing DMPC and cholesterol,
      whereas the interaction of CFP-10 with membranes appeared to be weaker and less
      specific. Most importantly, binding to the biomembranes no longer occurred when
      the proteins were present as a 1:1 ESAT-6.CFP-10 complex. However, lowering of
      the pH resulted in dissociation of the protein complex and subsequent protein
      liposome interaction. Finally, cryoelectron microscopy revealed that ESAT-6
      destabilized and lysed liposomes, whereas CFP-10 did not. In conclusion, we
      propose that one of the main features of ESAT-6 in the infection process of M.
      tuberculosis is the interaction with biomembranes that occurs after dissociation
      from its putative chaperone CFP-10 under acidic conditions typically encountered
      in the phagosome.

PMID- 17557818
TI  - Genomic characterization of the filamentous integrative bacteriophages {phi}RSS1
      and {phi}RSM1, which infect Ralstonia solanacearum.
AB  - The genomic DNA sequences were determined for two filamentous integrative
      bacteriophages, phiRSS1 and phiRSM1, of the phytopathogen Ralstonia solanacearum.
      The 6,662-base sequence of phiRSS1 contained 11 open reading frames (ORFs). In
      the databases, this sequence showed high homology (95% identity) to the circular
      double-stranded DNA plasmid pJTPS1 (6,633 bp) isolated from a spontaneously
      occurring avirulent mutant of R. solanacearum. Two major differences between the
      two sequences were observed within phiRSS1 ORF7, corresponding to pIII, a minor
      coat protein required for host adsorption, and at the phiRSS1 intergenic (IG)
      region. The 9,004-base sequence of phiRSM1 showed 12 ORFs located on the same
      strand (plus strand) and 2 ORFs on the opposite strand. Compared with Ff-type
      phages, two insertions are obvious in the phiRSM1 replication module. Genomic DNA
      fragments containing the phiRSM integration junctions were cloned and sequenced
      from phiRSM lysogenic strain R. solanacearum MAFF211270. The att core sequence
      was identified as 5'-TGGCGGAGAGGGT-3', corresponding to the 3' end of the serine
      tRNA (UCG) gene. Interestingly, ORF14, located next to the attP site on the
      phiRSM1 genome, showed high amino acid sequence homology with bacterial DNA
      recombinases and resolvases, different from XerCD recombinases. attP of phiRSS1
      is within a sequence element of the IG region.

PMID- 17557819
TI  - Transcriptional responses of Mycoplasma gallisepticum strain R in association
      with eukaryotic cells.
AB  - Mycoplasma gallisepticum is an etiologic agent of chronic respiratory disease in
      chickens and infectious sinusitis in turkeys. Other than proteins important for
      cytadherence, few M. gallisepticum factors or pathways contributing to host cell
      interactions have been identified. In this study, an oligonucleotide-based
      microarray was utilized to investigate transcriptional changes in M.
      gallisepticum strain R(low) upon exposure to eukaryotic cells. Fifty-eight genes
      were either up- or downregulated upon exposure to MRC-5 lung fibroblasts grown in
      vitro, including genes encoding transport-, metabolism-, and translation
      associated proteins. Twenty of the 58 regulated genes have no assigned function.
      These results indicate that M. gallisepticum regulates gene expression upon
      exposure to eukaryotic cells, revealing genes and pathways likely to be important
      for host-bacterium interaction.

PMID- 17557820
TI  - Complementation analysis of the cold-sensitive phenotype of the Escherichia coli
      csdA deletion strain.
AB  - The cold shock response of Escherichia coli is elicited by downshift of
      temperature from 37 degrees C to 15 degrees C and is characterized by induction
      of several cold shock proteins, including CsdA, during the acclimation phase.
      CsdA, a DEAD-box protein, has been proposed to participate in a variety of
      processes, such as ribosome biogenesis, mRNA decay, translation initiation, and
      gene regulation. It is not clear which of the functions of CsdA play a role in
      its essential cold shock function or whether all do, and so far no protein has
      been shown to complement its function in vivo. Our screening of an E. coli
      genomic library for an in vivo counterpart of CsdA that can compensate for its
      absence at low temperature revealed only one protein, RhlE, another DEAD-box RNA
      helicase. We also observed that although not detected in our genetic screening,
      two cold shock-inducible proteins, namely, CspA, an RNA chaperone, and RNase R,
      an exonuclease, can also complement the cold shock function of CsdA.
      Interestingly, the absence of CsdA and RNase R leads to increased sensitivity of
      the cells to even moderate temperature downshifts. The correlation between the
      helicase activity of CsdA and the stability of mRNAs of cold-inducible genes was
      shown using cspA mRNA, which was significantly stabilized in the DeltacsdA cells,
      an effect counteracted by overexpression of wild-type CsdA or RNase R but not by
      that of the helicase-deficient mutant of CsdA. These results suggest that the
      primary role of CsdA in cold acclimation of cells is in mRNA decay and that its
      helicase activity is pivotal for promoting degradation of mRNAs stabilized at low
      temperature.

PMID- 17557821
TI  - Filamentous morphology in GroE-depleted Escherichia coli induced by impaired
      folding of FtsE.
AB  - The chaperonin GroE (GroEL and the cochaperonin GroES) is the only chaperone
      system that is essential for the viability of Escherichia coli. It is known that
      GroE-depleted cells exhibit a filamentous morphology, suggesting that GroE is
      required for the folding of proteins involved in cell division. Although previous
      studies, including proteome-wide analyses of GroE substrates, have suggested
      several targets of GroE in cell division, there is no direct in vivo evidence to
      identify which substrates exhibit obligate dependence on GroE for folding. Among
      the candidate substrates, we found that prior excess production of FtsE, a
      protein engaged in cell division, completely suppressed the filamentation of GroE
      depleted E. coli. The GroE depletion led to a drastic decrease in FtsE, and the
      cells exhibited a known phenotype associated with impaired FtsE function. In the
      GroE-depleted filamentous cells, the localizations of FtsA and ZipA, both of
      which assemble with the FtsZ septal ring before FtsE, were normal, whereas FtsX,
      the interaction partner of FtsE, and FtsQ, which is recruited after FtsE, did not
      localize to the ring, suggesting that the decrease in FtsE is a cause of the
      filamentous morphology. Finally, a reconstituted cell-free translation system
      revealed that the folding of newly translated FtsE was stringently dependent on
      GroEL/GroES. Based on these findings, we concluded that FtsE is a target
      substrate of the GroE system in E. coli cell division.

PMID- 17557822
TI  - folA, a new member of the TyrR regulon in Escherichia coli K-12.
AB  - The folA gene was identified as a new member of the TyrR regulon by genomic
      SELEX. Binding of TyrR to two sites in folA activated its transcription.
      Mutations in the N-terminal or central domain of TyrR, the alpha subunit of RNA
      polymerase, or integration host factor all abolished activation of the folA
      promoter.

PMID- 17557823
TI  - Coupling of fatty acid and phospholipid synthesis in Bacillus subtilis.
AB  - plsX (acyl-acyl carrier protein [ACP]:phosphate acyltransferase), plsY (yneS)
      (acyl-phosphate:glycerol-phosphate acyltransferase), and plsC (yhdO) (acyl-ACP:1
      acylglycerol-phosphate acyltransferase) function in phosphatidic acid formation,
      the precursor to membrane phospholipids. The physiological functions of these
      genes was inferred from their in vitro biochemical activities, and this study
      investigated their roles in gram-positive phospholipid metabolism through the
      analysis of conditional knockout strains in the Bacillus subtilis model system.
      The depletion of PlsX led to the cessation of both fatty acid synthesis and
      phospholipid synthesis. The inactivation of PlsY also blocked phospholipid
      synthesis, but fatty acid formation continued due to the appearance of
      acylphosphate intermediates and fatty acids arising from their hydrolysis.
      Phospholipid synthesis ceased following PlsC depletion, but fatty acid synthesis
      continued at a high rate, leading to the accumulation of fatty acids arising from
      the dephosphorylation of 1-acylglycerol-3-P followed by the deacylation of
      monoacylglycerol. Analysis of glycerol 3-P acylation in B. subtilis membranes
      showed that PlsY was an acylphosphate-specific acyltransferase, whereas PlsC used
      only acyl-ACP as an acyl donor. PlsX was found in the soluble fraction of
      disrupted cells but was associated with the cell membrane in intact organisms.
      These data establish that PlsX is a key enzyme that coordinates the production of
      fatty acids and membrane phospholipids in B. subtilis.

PMID- 17557824
TI  - Binding of human plasminogen to Bifidobacterium.
AB  - Bifidobacteria constitute up to 3% of the total microbiota and represent one of
      the most important health-promoting bacterial groups of the human intestinal
      microflora. The presence of Bifidobacterium in the human gastrointestinal tract
      has been directly related to several health-promoting activities; however, to
      date, no information about the specific mechanisms of interaction with the host
      is available. In order to provide some insight into the molecular mechanisms
      involved in the interaction with the host, we investigated whether
      Bifidobacterium was able to capture human plasminogen on the cell surface. By
      using flow cytometry, we demonstrated a dose-dependent human plasminogen-binding
      activity for four strains belonging to three bifidobacterial species:
      Bifidobacterium lactis, B. bifidum, and B. longum. The binding of human
      plasminogen to Bifidobacterium was dependent on lysine residues of surface
      protein receptors. By using a proteomic approach, we identified five putative
      plasminogen-binding proteins in the cell wall fraction of the model strain B.
      lactis BI07. The data suggest that plasminogen binding to B. lactis is due to the
      concerted action of a number of proteins located on the bacterial cell surface,
      some of which are highly conserved cytoplasmic proteins which have other
      essential cellular functions. Our findings represent a step forward in
      understanding the mechanisms involved in the Bifidobacterium-host interaction.

PMID- 17557825
TI  - Mutations of the quorum sensing-dependent regulator VjbR lead to drastic surface
      modifications in Brucella melitensis.
AB  - Successful establishment of infection by bacterial pathogens requires fine-tuning
      of virulence-related genes. Quorum sensing (QS) is a global regulation process
      based on the synthesis of, detection of, and response to small diffusible
      molecules, called N-acyl-homoserine lactones (AHL), in gram-negative bacteria. In
      numerous species, QS has been shown to regulate genes involved in the
      establishment of pathogenic interactions with the host. Brucella melitensis
      produces N-dodecanoyl homoserine lactones (C(12)-HSL), which down regulate the
      expression of flagellar genes and of the virB operon (encoding a type IV
      secretion system), both of which encode surface virulence factors. A QS-related
      regulator, called VjbR, was identified as a transcriptional activator of these
      genes. We hypothesized that VjbR mediates the C(12)-HSL effects described above.
      vjbR alleles mutated in the region coding for the AHL binding domain were
      constructed to test this hypothesis. These alleles expressed in trans in a
      DeltavjbR background behave as constitutive regulators both in vitro and in a
      cellular model of infection. Interestingly, the resulting B. melitensis strains,
      unable to respond to AHLs, aggregate spontaneously in liquid culture. Preliminary
      characterization of these strains showed altered expression of some outer
      membrane proteins and overproduction of a matrix-forming exopolysaccharide,
      suggesting for the first time that B. melitensis could form biofilms. Together,
      these results indicate that QS through VjbR is a major regulatory system of
      important cell surface structures of Brucella and as such plays a key role in
      host-pathogen interactions.

PMID- 17557826
TI  - SpoIVB and CtpB are both forespore signals in the activation of the sporulation
      transcription factor sigmaK in Bacillus subtilis.
AB  - The proteolytic activation of the mother cell transcription factor pro-sigma(K)
      is controlled by a signal transduction pathway during sporulation in the
      bacterium Bacillus subtilis. The pro-sigma(K) processing enzyme SpoIVFB, a
      membrane-embedded metalloprotease, is held inactive by two other integral
      membrane proteins, SpoIVFA and BofA, in the mother cell membrane that surrounds
      the forespore. Two signaling serine proteases, SpoIVB and CtpB, trigger pro
      sigma(K) processing by cleaving the regulatory protein SpoIVFA. The SpoIVB signal
      is absolutely required to activate pro-sigma(K) processing and is derived from
      the forespore compartment. CtpB is necessary for the proper timing of sigma(K)
      activation and was thought to be a mother cell signal. Here, we show that the
      ctpB gene is expressed in both the mother cell and forespore compartments but
      that synthesis in the forespore under the control of sigma(G) is both necessary
      and sufficient for the proper timing of pro-sigma(K) processing. We further show
      that SpoIVB cleaves CtpB in vitro and in vivo but that this cleavage does not
      appear to be necessary for CtpB activation. Thus, both signaling proteins are
      made in the forespore and independently target the same regulatory protein.

PMID- 17557827
TI  - Quorum sensing in Escherichia coli is signaled by AI-2/LsrR: effects on small RNA
      and biofilm architecture.
AB  - The regulatory network for the uptake of Escherichia coli autoinducer 2 (AI-2) is
      comprised of a transporter complex, LsrABCD; its repressor, LsrR; and a cognate
      signal kinase, LsrK. This network is an integral part of the AI-2 quorum-sensing
      (QS) system. Because LsrR and LsrK directly regulate AI-2 uptake, we hypothesized
      that they might play a wider role in regulating other QS-related cellular
      functions. In this study, we characterized physiological changes due to the
      genomic deletion of lsrR and lsrK. We discovered that many genes were coregulated
      by lsrK and lsrR but in a distinctly different manner than that for the lsr
      operon (where LsrR serves as a repressor that is derepressed by the binding of
      phospho-AI-2 to the LsrR protein). An extended model for AI-2 signaling that is
      consistent with all current data on AI-2, LuxS, and the LuxS regulon is proposed.
      Additionally, we found that both the quantity and architecture of biofilms were
      regulated by this distinct mechanism, as lsrK and lsrR knockouts behaved
      identically. Similar biofilm architectures probably resulted from the concerted
      response of a set of genes including flu and wza, the expression of which is
      influenced by lsrRK. We also found for the first time that the generation of
      several small RNAs (including DsrA, which was previously linked to QS systems in
      Vibrio harveyi) was affected by LsrR. Our results suggest that AI-2 is indeed a
      QS signal in E. coli, especially when it acts through the transcriptional
      regulator LsrR.

PMID- 17557828
TI  - Staphylococcus aureus ArcR controls expression of the arginine deiminase operon.
AB  - We identified a single open reading frame that is strongly similar to ArcR, a
      member of the Crp/Fnr family of bacterial transcriptional regulators, in all
      sequenced Staphylococcus aureus genomes. The arcR gene encoding ArcR forms an
      operon with the arginine deiminase (ADI) pathway genes arcABDC that enable the
      utilization of arginine as a source of energy for growth under anaerobic
      conditions. In this report, we show that under anaerobic conditions, S. aureus
      growth is subject to glucose catabolic repression and is enhanced by arginine.
      Likewise, glucose and arginine have reciprocal effects on the transcription of
      the arcABDCR genes. Furthermore, we show using a mutant deleted for arcR that the
      transcription of the arc operon under anaerobic conditions depends strictly on a
      functional ArcR. These findings are supported by proteome analyses, which showed
      that under anaerobic conditions the expression of the ADI catabolic proteins
      depends on ArcR. Bioinformatic analysis of S. aureus ArcR predicts an N-terminal
      nucleotide binding domain and a C-terminal helix-turn-helix DNA binding motif.
      ArcR binds to a conserved Crp-like sequence motif, TGTGA-N(6)-TCACA, present in
      the arc promoter region and thereby activates the expression of the ADI pathway
      genes. Crp-like sequence motifs were also found in the regulatory regions of some
      30 other S. aureus genes mostly encoding anaerobic enzymatic systems, virulence
      factors, and regulatory systems. ArcR was tested and found to bind to the
      regulatory regions of four such genes, adh1, lctE, srrAB, and lukM. In one case,
      for lctE, encoding l-lactate dehydrogenase, ArcR was able to bind only in the
      presence of cyclic AMP. These observations suggest that ArcR is likely to play an
      important role in the expression of numerous genes required for anaerobic growth.

PMID- 17557829
TI  - Escherichia coli malic enzymes: two isoforms with substantial differences in
      kinetic properties, metabolic regulation, and structure.
AB  - Malic enzymes (MEs) catalyze the oxidative decarboxylation of malate in the
      presence of a divalent metal ion. In eukaryotes, well-conserved cytoplasmic,
      mitochondrial, and plastidic MEs have been characterized. On the other hand,
      distinct groups can be detected among prokaryotic MEs, which are more diverse in
      structure and less well characterized than their eukaryotic counterparts. In
      Escherichia coli, two genes with a high degree of homology to ME can be detected:
      sfcA and maeB. MaeB possesses a multimodular structure: the N-terminal extension
      shows homology to ME, while the C-terminal extension shows homology to
      phosphotransacetylases (PTAs). In the present work, a detailed characterization
      of the products of E. coli sfcA and maeB was performed. The results indicate that
      the two MEs exhibit relevant kinetic, regulatory, and structural differences.
      SfcA is a NAD(P) ME, while MaeB is a NADP-specific ME highly regulated by key
      metabolites. Characterization of truncated versions of MaeB indicated that the
      PTA domain is not essential for the ME reaction. Nevertheless, truncated MaeB
      without the PTA domain loses most of its metabolic ME modulation and its native
      oligomeric state. Thus, the association of the two structural domains in MaeB
      seems to facilitate metabolic control of the enzyme. Although the PTA domain in
      MaeB is highly similar to the domains of proteins with PTA activity, MaeB and its
      PTA domain do not exhibit PTA activity. Determination of the distinct properties
      of recombinant products of sfcA and maeB performed in the present work will help
      to clarify the roles of MEs in prokaryotic metabolism.

PMID- 17557830
TI  - Dominant role of the cbb3 oxidase in regulation of photosynthesis gene expression
      through the PrrBA system in Rhodobacter sphaeroides 2.4.1.
AB  - In this study, the H303A mutant form of the cbb(3) oxidase (H303A oxidase), which
      has the H303A mutation in its catalytic subunit (CcoN), was purified from
      Rhodobacter sphaeroides. The H303A oxidase showed the same catalytic activity as
      did the wild-type form of the oxidase (WT oxidase). The heme contents of the
      mutant and WT forms of the cbb(3) oxidase were also comparable. However, the puf
      and puc operons, which are under the control of the PrrBA two-component system,
      were shown to be derepressed aerobically in the R. sphaeroides strain expressing
      the H303A oxidase. Since the strain harboring the H303A oxidase exhibited the
      same cytochrome c oxidase activity as the stain harboring the WT oxidase did, the
      aerobic derepression of photosynthesis gene expression observed in the H303A
      mutant appears to be the result of a defective signaling function of the H303A
      oxidase rather than reflecting any redox changes in the ubiquinone/ubiquinol
      pool. It was also demonstrated that ubiquinone inhibits not only the autokinase
      activity of full-length PrrB but also that of the truncated form of PrrB lacking
      its transmembrane domain, including the proposed quinone binding sequence. These
      results imply that the suggested ubiquinone binding site within the PrrB
      transmembrane domain is not necessary for the inhibition of PrrB kinase activity
      by ubiquinone. Instead, it is probable that signaling through H303 of the CcoN
      subunit of the cbb(3) oxidase is part of the pathway through which the cbb(3)
      oxidase affects the relative kinase/phosphatase activity of the membrane-bound
      PrrB.

PMID- 17557831
TI  - Molecular characterization of membrane-associated soluble serine
      palmitoyltransferases from Sphingobacterium multivorum and Bdellovibrio stolpii.
AB  - Serine palmitoyltransferase (SPT) is a key enzyme in sphingolipid biosynthesis
      and catalyzes the decarboxylative condensation of l-serine and palmitoyl coenzyme
      A (CoA) to form 3-ketodihydrosphingosine (KDS). Eukaryotic SPTs comprise tightly
      membrane-associated heterodimers belonging to the pyridoxal 5'-phosphate (PLP)
      dependent alpha-oxamine synthase family. Sphingomonas paucimobilis, a
      sphingolipid-containing bacterium, contains an abundant water-soluble homodimeric
      SPT of the same family (H. Ikushiro et al., J. Biol. Chem. 276:18249-18256,
      2001). This enzyme is suitable for the detailed mechanistic studies of SPT,
      although single crystals appropriate for high-resolution crystallography have not
      yet been obtained. We have now isolated three novel SPT genes from
      Sphingobacterium multivorum, Sphingobacterium spiritivorum, and Bdellovibrio
      stolpii, respectively. Each gene product exhibits an approximately 30% sequence
      identity to both eukaryotic subunits, and the putative catalytic amino acid
      residues are conserved. All bacterial SPTs were successfully overproduced in
      Escherichia coli and purified as water-soluble active homodimers. The
      spectroscopic properties of the purified SPTs are characteristic of PLP-dependent
      enzymes. The KDS formation by the bacterial SPTs was confirmed by high
      performance liquid chromatography/mass spectrometry. The Sphingobacterium SPTs
      obeyed normal steady-state ordered Bi-Bi kinetics, while the Bdellovibrio SPT
      underwent a remarkable substrate inhibition at palmitoyl CoA concentrations
      higher than 100 microM, as does the eukaryotic enzyme. Immunoelectron microscopy
      showed that unlike the cytosolic Sphingomonas SPT, S. multivorum and Bdellovibrio
      SPTs were bound to the inner membrane of cells as peripheral membrane proteins,
      indicating that these enzymes can be a prokaryotic model mimicking the membrane
      associated eukaryotic SPT.

PMID- 17557832
TI  - Comparative analysis of expressed genes from cacao meristems infected by
      Moniliophthora perniciosa.
AB  - BACKGROUND AND AIMS: Witches' broom disease is caused by the hemibiotrophic
      basidiomycete Moniliophthora perniciosa, and is one of the most important
      diseases of cacao in the western hemisphere. Because very little is known about
      the global process of such disease development, expressed sequence tags (ESTs)
      were used to identify genes expressed during the Theobroma cacao-Moniliophthora
      perniciosa interaction. METHODS: Two cDNA libraries corresponding to the
      resistant (RT) and susceptible (SP) cacao-M. perniciosa interactions were
      constructed from total RNA, using the DB SMART Creator cDNA library kit
      (Clontech). Clones were randomly selected, sequenced from the 5' end and analysed
      using bioinformatics tools including in silico analysis of the differential gene
      expression. KEY RESULTS: A total of 6884 ESTs were generated from the RT and SP
      cDNA libraries. These ESTs were composed of 2585 singlets and 341 contigs for a
      total of 2926 non-redundant sequences. The redundancy of the libraries was low
      and their specificity high when compared with the few other cacao libraries
      already published. Sequence analysis allowed the assignment of a putative
      functional category for 54 % of sequences, whereas approx. 22 % of sequences
      corresponded to unknown function and approx. 24 % of sequences did not show any
      significant similarity with other proteins present in the database. Despite the
      similar overall distribution of the sequences in functional categories between
      the two libraries, qualitative differences were observed. Genes involved during
      the defence response to pathogen infection or in programmed cell death were
      identified, such as pathogenesis related-proteins, trypsin inhibitor or oxalate
      oxidase, and some of them showed an in silico differential expression between the
      resistant and the susceptible interactions. CONCLUSIONS: As far as is known this
      is the first EST resource from the cacao-M. perniciosa interaction and it is
      believed that it will provide a significant contribution to the understanding of
      the molecular mechanisms of the resistance and susceptibility of cacao to M.
      perniciosa, to develop strategies to control witches' broom, and as a source of
      polymorphism for molecular marker development and marker-assisted selection.

PMID- 17557833
TI  - Floral ontogeny of the Afro-Madagascan genus Mitrasacmopsis with comments on the
      development of superior ovaries in Rubiaceae.
AB  - BACKGROUND AND AIMS: Members of Rubiaceae are generally characterized by an
      inferior ovary. However, Mitrasacmopsis is cited in the literature as having a
      semi-inferior to superior ovary. It has previously been hypothesized that the
      gynoecial development of Rubiaceae with semi-inferior to superior ovaries takes
      place in the same way as in Gaertnera, one of the most commonly cited rubiaceous
      genera with a superior ovary. To test this hypothesis, a floral ontogenetic study
      of Mitrasacmopsis was carried out with special attention paid to the gynoecial
      development. METHODS: Floral ontogeny and anatomy of Mitrasacmopsis were examined
      using scanning electron and light microscopy. KEY RESULTS: At an early
      developmental stage, a concavity becomes visible in the centre of the floral apex
      simultaneously with the perianth initiation. A ring primordium surrounding this
      concavity expands vertically forming the corolla tube (early sympetaly). Stamen
      primordia develop inside the corolla. From the bicarpellate gynoecium only two
      carpel tips are visible because the ovary is formed by a gynoecial hypanthium. In
      the basal part of each carpel, a placenta primordium is initiated. Two septa
      divide the ovary into two locules. In each locule, the placenta becomes mushroom
      shaped and distinctly stalked. Eventually, the inferior ovary of Mitrasacmopsis
      develops into a beaked capsule. Only very late in the fruiting stage, the
      continuously expanding ovary is raised above the insertion point of the
      persistent calyx, changing the ovary position of Mitrasacmopsis from basically
      inferior to secondarily semi-inferior. CONCLUSIONS: Mitrasacmopsis follows an
      epigynous pattern of floral development. However, the presence of a prominent
      beak in the fruiting stage gives the whole ovary a semi-inferior appearance. This
      kind of secondarily semi-inferior ovary is shown to be different from the
      secondarily superior ovary observed in Gaertnera.

PMID- 17557834
TI  - Possible rabies exposures require expert clinical assessment.

PMID- 17557835
TI  - Bmi-1 is a target gene for SALL4 in hematopoietic and leukemic cells.
AB  - Bmi-1 and SALL4 are putative oncogenes that modulate stem cell pluripotency and
      play a role in leukemogenesis. Murine Sall4 also has been shown to play an
      essential role in maintaining the properties of ES cells and governing the fate
      of the primitive inner cell mass. Here, we demonstrate that transcription from
      the Bmi-1 promoter is strikingly activated by SALL4 in a dose-dependent manner by
      using a luciferase reporter gene assay. Both promoter deletion construct studies
      and ChIP from a myeloid stem cell line, 32D, demonstrate that SALL4 binds to a
      specific region of the Bmi-1 promoter. Deletion of one copy of Sall4 by gene
      targeting in mouse bone marrow significantly reduced Bmi-1 expression. Reducing
      SALL4 expression by siRNA in the HL-60 leukemia cell line also results in
      significant down-regulation of Bmi-1. Furthermore, Bmi-1 expression is up
      regulated in transgenic mice that constitutively overexpress human SALL4, and the
      levels of Bmi-1 in these mice increase as they progress from normal to
      preleukemic (myelodysplastic syndrome) and leukemic (acute myeloid leukemia)
      stages. High levels of H3-K4 trimethylation and H3-K79 dimethylation were
      observed in the SALL4 binding region of the Bmi-1 promoter. These findings
      suggest a novel link between SALL4 and Bmi-1 in regulating self-renewal of normal
      and leukemic stem cells. An increase in histone H3-K4 and H3-K79 methylation
      within the Bmi-1 promoter provides an epigenetic mechanism for histone
      modifications in SALL4-mediated Bmi-1 gene deregulation.

PMID- 17557837
TI  - A relaxation-assisted 2D IR spectroscopy method.
AB  - A method of two-dimensional infrared (2D IR) spectroscopy called relaxation
      assisted 2D IR (RA 2DIR) is proposed that utilizes vibrational energy relaxation
      transport in molecules to enhance cross-peak amplitudes. This method
      substantially increases the range of distances accessible by 2D IR and is capable
      of identifying long-range connectivity patterns in molecules. RA 2DIR is
      illustrated in interactions among CN and CO modes in 3-cyanocoumarin and 4
      acetylbenzonitrile, where the distances between the CN and CO groups are
      approximately 3.1 and approximately 6.5 A, respectively. A 6-fold increase in
      cross-peak amplitude was observed in 4-acetylbenzonitrile when the dual-frequency
      RA 2DIR method was used.

PMID- 17557836
TI  - Centromeres were derived from telomeres during the evolution of the eukaryotic
      chromosome.
AB  - The centromere is the DNA region of the eukaryotic chromosome that determines
      kinetochore formation and sister chromatid cohesion. Centromeres interact with
      spindle microtubules to ensure the segregation of chromatids during mitosis and
      of homologous chromosomes in meiosis. The origin of centromeres, therefore, is
      inseparable from the evolution of cytoskeletal components that distribute
      chromosomes to offspring cells. Although the origin of the nucleus has been
      debated, no explanation for the evolutionary appearance of centromeres is
      available. We propose an evolutionary scenario: The centromeres originated from
      telomeres. The breakage of the ancestral circular genophore activated the
      transposition of retroelements at DNA ends that allowed the formation of
      telomeres by a recombination-dependent replication mechanism. Afterward, the
      modification of the tubulin-based cytoskeleton that allowed specific subtelomeric
      repeats to be recognized as new cargo gave rise to the first centromere. This
      switch from actin-based genophore partition to a tubulin-based mechanism
      generated a transition period during which both types of cytoskeleton contributed
      to fidelity of chromosome segregation. During the transition, pseudodicentric
      chromosomes increased the tendency toward chromosomal breakage and instability.
      This instability generated multiple telocentric chromosomes that eventually
      evolved into metacentric or holocentric chromosomes.

PMID- 17557838
TI  - Identification of human-pathogenic strains of Shiga toxin-producing Escherichia
      coli from food by a combination of serotyping and molecular typing of Shiga toxin
      genes.
AB  - We examined 219 Shiga toxin-producing Escherichia coli (STEC) strains from meat,
      milk, and cheese samples collected in Germany between 2005 and 2006. All strains
      were investigated for their serotypes and for genetic variants of Shiga toxins 1
      and 2 (Stx1 and Stx2). stx(1) or variant genes were detected in 88 (40.2%)
      strains and stx(2) and variants in 177 (80.8%) strains. Typing of stx genes was
      performed by stx-specific PCRs and by analysis of restriction fragment length
      polymorphisms (RFLP) of PCR products. Major genotypes of the Stx1 (stx(1),
      stx(1c), and stx(1d)) and the Stx2 (stx(2), stx(2d), stx(2-O118), stx(2e), and
      stx(2g)) families were detected, and multiple types of stx genes coexisted
      frequently in STEC strains. Only 1.8% of the STEC strains from food belonged to
      the classical enterohemorrhagic E. coli (EHEC) types O26:H11, O103:H2, and
      O157:H7, and only 5.0% of the STEC strains from food were positive for the eae
      gene, which is a virulence trait of classical EHEC. In contrast, 95 (43.4%) of
      the food-borne STEC strains carried stx(2) and/or mucus-activatable stx(2d)
      genes, an indicator for potential high virulence of STEC for humans. Most of
      these strains belonged to serotypes associated with severe illness in humans,
      such as O22:H8, O91:H21, O113:H21, O174:H2, and O174:H21. stx(2) and stx(2d) STEC
      strains were found frequently in milk and beef products. Other stx types were
      associated more frequently with pork (stx(2e)), lamb, and wildlife meat
      (stx(1c)). The combination of serotyping and stx genotyping was found useful for
      identification and for assignment of food-borne STEC to groups with potential
      lower and higher levels of virulence for humans.

PMID- 17557839
TI  - Parvibaculum lavamentivorans DS-1T degrades centrally substituted congeners of
      commercial linear alkylbenzenesulfonate to sulfophenyl carboxylates and
      sulfophenyl dicarboxylates.
AB  - Commercial linear alkylbenzenesulfonate (LAS) contains 20 congeners of linear
      alkanes (C(10) to C(13)) substituted subterminally with the 4-sulfophenyl moiety
      in any position from lateral to central. Parvibaculum lavamentivorans DS-1(T)
      degrades each of eight laterally substituted congeners [e.g., 2-(4
      sulfophenyl)decane (2-C10-LAS); herein, compounds are named systematically by
      chain length (e.g., C(10)) and by the position of the substituent on the chain
      (e.g., position 2)] to a major sulfophenyl carboxylate [SPC; here 3-(4
      sulfophenyl)butyrate (3-C4-SPC)] and two minor products, namely, the alpha,beta
      unsaturated SPC (SPC-2H, here 3-C4-SPC-2H) and the SPC+2C (here 5-C6-SPC) species
      (D. Schleheck, T. P. Knepper, K. Fischer, and A. M. Cook, Appl. Environ.
      Microbiol. 70:4053-4063). The degradation of centrally substituted congeners by
      strain DS-1 was examined in this work. 5-C10-LAS yielded not only the predicted 4
      C8-SPC, 4-C8-SPC-2H, and 6-C10-SPC (about 70% of products) but also sulfophenyl
      dicarboxylates (SPdC), i.e., C6-, C8-, and C10-SPdC. These were identified by
      electrospray ionization-mass spectrometry (ESI-MS) after separation by high
      pressure liquid chromatography (HPLC). ESI ion-trap MS and ESI-time of flight-MS
      were used to confirm the identities of key intermediates. Different mixtures of
      congeners obtained by separation of commercial LAS by HPLC were degraded, and the
      degradative products were compared. If a congener carried the sulfophenyl
      substituent on the 5, 6, or 7 position, SPdCs were formed as well as SPC, SPC-2H,
      and SPC+2C, whereas the substituent on the 2, 3, or 4 position yielded only SPC,
      SPC-2H, and SPC+2C. Some 50 products were generated from the 20 LAS congeners: 11
      major SPCs, each with an SPC-2H and an SPC+2C (i.e., 33 SPC and SPC-2H species),
      and about 17 SPdC species. A large array of compounds, many in low quantities, is
      thus generated by P. lavamentivorans DS-1 during the degradation of commercial
      LAS.

PMID- 17557840
TI  - Degradation pathway of bisphenol A: does ipso substitution apply to phenols
      containing a quaternary alpha-carbon structure in the para position?
AB  - The degradation of bisphenol A and nonylphenol involves the unusual rearrangement
      of stable carbon-carbon bonds. Some nonylphenol isomers and bisphenol A possess a
      quaternary alpha-carbon atom as a common structural feature. The degradation of
      nonylphenol in Sphingomonas sp. strain TTNP3 occurs via a type II ipso
      substitution with the presence of a quaternary alpha-carbon as a prerequisite. We
      report here a new degradation pathway of bisphenol A. Consequent to the
      hydroxylation at position C-4, according to a type II ipso substitution
      mechanism, the C-C bond between the phenolic moiety and the isopropyl group of
      bisphenol A is broken. Besides the formation of hydroquinone and 4-(2
      hydroxypropan-2-yl)phenol as the main metabolites, further compounds resulting
      from molecular rearrangements consistent with a carbocationic intermediate were
      identified. Assays with resting cells or cell extracts of Sphingomonas sp. strain
      TTNP3 under an (18)O(2) atmosphere were performed. One atom of (18)O(2) was
      present in hydroquinone, resulting from the monooxygenation of bisphenol A and
      nonylphenol. The monooxygenase activity was dependent on both NADPH and flavin
      adenine dinucleotide. Various cytochrome P450 inhibitors had identical inhibition
      effects on the conversion of both xenobiotics. Using a mutant of Sphingomonas sp.
      strain TTNP3, which is defective for growth on nonylphenol, we demonstrated that
      the reaction is catalyzed by the same enzymatic system. In conclusion, the
      degradation of bisphenol A and nonylphenol is initiated by the same
      monooxygenase, which may also lead to ipso substitution in other xenobiotics
      containing phenol with a quaternary alpha-carbon.

PMID- 17557841
TI  - Evidence of temporal postdischarge decontamination of bacteria by gliding
      electric discharges: application to Hafnia alvei.
AB  - This study aimed to characterize the bacterium-destroying properties of a gliding
      arc plasma device during electric discharges and also under temporal
      postdischarge conditions (i.e., when the discharge was switched off). This
      phenomenon was reported for the first time in the literature in the case of the
      plasma destruction of microorganisms. When cells of a model bacterium, Hafnia
      alvei, were exposed to electric discharges, followed or not followed by temporal
      postdischarges, the survival curves exhibited a shoulder and then log-linear
      decay. These destruction kinetics were modeled using GinaFiT, a freeware tool to
      assess microbial survival curves, and adjustment parameters were determined. The
      efficiency of postdischarge treatments was clearly affected by the discharge time
      (t*); both the shoulder length and the inactivation rate k(max) were linearly
      modified as a function of t*. Nevertheless, all conditions tested (t* ranging
      from 2 to 5 min) made it possible to achieve an abatement of at least 7 decimal
      logarithm units. Postdischarge treatment was also efficient against bacteria not
      subjected to direct discharge, and the disinfecting properties of "plasma
      activated water" were dependent on the treatment time for the solution. Water
      treated with plasma for 2 min achieved a 3.7-decimal-logarithm-unit reduction in
      20 min after application to cells, and abatement greater than 7 decimal logarithm
      units resulted from the same contact time with water activated with plasma for 10
      min. These disinfecting properties were maintained during storage of activated
      water for 30 min. After that, they declined as the storage time increased.

PMID- 17557842
TI  - Identification and isolation of a Castellaniella species important during
      biostimulation of an acidic nitrate- and uranium-contaminated aquifer.
AB  - Immobilization of uranium in groundwater can be achieved through microbial
      reduction of U(VI) to U(IV) upon electron donor addition. Microbial community
      structure was analyzed in ethanol-biostimulated and control sediments from a high
      nitrate (>130 mM), low-pH, uranium-contaminated site in Oak Ridge, TN. Analysis
      of small subunit (SSU) rRNA gene clone libraries and polar lipid fatty acids from
      sediments revealed that biostimulation resulted in a general decrease in
      bacterial diversity. Specifically, biostimulation resulted in an increase in the
      proportion of Betaproteobacteria (10% of total clones in the control sediment
      versus 50 and 79% in biostimulated sediments) and a decrease in the proportion of
      Gammaproteobacteria and Acidobacteria. Clone libraries derived from dissimilatory
      nitrite reductase genes (nirK and nirS) were also dominated by clones related to
      Betaproteobacteria (98% and 85% of total nirK and nirS clones, respectively).
      Within the nirK libraries, one clone sequence made up 59 and 76% of sequences
      from biostimulated sediments but only made up 10% of the control nirK library.
      Phylogenetic analysis of SSU rRNA and nirK gene sequences from denitrifying pure
      cultures isolated from the site indicate that all belong to a Castellaniella
      species; nearly identical sequences also constituted the majority of
      biostimulated SSU rRNA and nirK clone libraries. Thus, by combining culture
      independent with culture-dependent techniques, we were able to link SSU rRNA
      clone library information with nirK sequence data and conclude that a potentially
      novel Castellaniella species is important for in situ nitrate removal at this
      site.

PMID- 17557843
TI  - Putative porin of Bradyrhizobium sp. (Lupinus) bacteroids induced by glyphosate.
AB  - Application of glyphosate (N-[phosphonomethyl] glycine) to Bradyrhizobium sp.
      (Lupinus)-nodulated lupin plants caused modifications in the protein pattern of
      bacteroids. The most significant change was the presence of a 44-kDa polypeptide
      in bacteroids from plants treated with the higher doses of glyphosate employed (5
      and 10 mM). The polypeptide has been characterized by the amino acid sequencing
      of its N terminus and the isolation and nucleic acid sequencing of its encoding
      gene. It is putatively encoded by a single gene, and the protein has been
      identified as a putative porin. Protein modeling revealed the existence of
      several domains sharing similarity to different porins, such as a transmembrane
      beta-barrel. The protein has been designated BLpp, for Bradyrhizobium sp.
      (Lupinus) putative porin, and would be the first porin described in
      Bradyrhizobium sp. (Lupinus). In addition, a putative conserved domain of porins
      has been identified which consists of 87 amino acids, located in the BLpp
      sequence 30 amino acids downstream of the N-terminal region. In bacteroids, mRNA
      of the BLpp gene shows a basal constitutive expression that increases under
      glyphosate treatment, and the expression of the gene is seemingly regulated at
      the transcriptional level. By contrast, in free-living bacteria glyphosate
      treatment leads to an inhibition of BLpp mRNA accumulation, indicating a
      different effect of glyphosate on BLpp gene expression in bacteroids and free
      living bacteria. The possible role of BLpp in a metabolite interchange between
      Bradyrhizobium and lupin is discussed.

PMID- 17557844
TI  - Metal ions may suppress or enhance cellular differentiation in Candida albicans
      and Candida tropicalis biofilms.
AB  - Candida albicans and Candida tropicalis are polymorphic fungi that develop
      antimicrobial-resistant biofilm communities that are characterized by multiple
      cell morphotypes. This study investigated cell type interconversion and drug and
      metal resistance as well as community organization in biofilms of these
      microorganisms that were exposed to metal ions. To study this, Candida biofilms
      were grown either in microtiter plates containing gradient arrays of metal ions
      or in the Calgary Biofilm Device for high-throughput susceptibility testing.
      Biofilm formation and antifungal resistance were evaluated by viable cell counts,
      tetrazolium salt reduction, light microscopy, and confocal laser scanning
      microscopy in conjunction with three-dimensional visualization. We discovered
      that subinhibitory concentrations of certain metal ions (CrO(4)(2-), Co(2+),
      Cu(2+), Ag(+), Zn(2+), Cd(2+), Hg(2+), Pb(2+), AsO(2)(-), and SeO(3)(2-)) caused
      changes in biofilm structure by blocking or eliciting the transition between
      yeast and hyphal cell types. Four distinct biofilm community structure types were
      discerned from these data, which were designated "domed," "layer cake," "flat,"
      and "mycelial." This study suggests that Candida biofilm populations may respond
      to metal ions to form cell-cell and solid-surface-attached assemblages with
      distinct patterns of cellular differentiation.

PMID- 17557845
TI  - Real-time reverse transcription-PCR for transcriptional expression analysis of
      virulence and housekeeping genes in viable but nonculturable Vibrio
      parahaemolyticus after recovery of culturability.
AB  - A real-time reverse transcription-PCR method was developed to determine whether
      the recovery of culturability of viable but nonculturable (VBNC) Vibrio
      parahaemolyticus induced the expression of virulence genes coding for the
      thermostable direct hemolysin and for type III secretion system 2 (TTSS2). The
      culturability of clinical strain Vp5 of V. parahaemolyticus in artificial
      seawater at 4 degrees C was monitored, and the VBNC state was obtained. One day
      after entry into the VBNC state, temperature upshifts to 20 and 37 degrees C
      allowed the recovery of culturability. Standard curves for the relative
      quantification of expression of the housekeeping genes rpoS, pvsA, fur, and pvuA;
      the tdh2 gene; and the TTSS2 genes (VPA1354, VPA1346, and VPA1342) were
      established. The levels of expression of the pvsA and pvuA genes were stable and
      were used to normalize the levels of expression of the other genes. No
      transcriptional induction of the selected virulence genes under the temperature
      conditions used to recover the culturability of the VBNC bacteria was observed.
      The study results demonstrate that the recovery of culturability of VBNC cells of
      pathogenic V. parahaemolyticus is restricted to regrowth, without correlation
      with the induction of virulence gene expression. Disease induction would depend
      mainly on host-pathogen interactions that allow the expression of the virulence
      genes. This is the first time that the use of mRNA to detect viable cells was
      evaluated by computing the half-lives of multiple mRNA species under conditions
      inducing the VBNC state.

PMID- 17557846
TI  - Overexpression of the calcineurin target CRZ1 provides freeze tolerance and
      enhances the fermentative capacity of baker's yeast.
AB  - Recent years have shown a huge growth in the market of industrial baker's yeasts
      (Saccharomyces cerevisiae), with the need for strains affording better
      performance in prefrozen dough. Evidence suggests that during the freezing
      process, cells can suffer biochemical damage caused by osmotic stress.
      Nevertheless, the involvement of ion-responsive transcriptional factors and
      pathways in conferring freeze resistance has not yet been examined. Here, we have
      investigated the role of the salt-responsive calcineurin-Crz1p pathway in
      mediating tolerance to freezing by industrial baker's yeast. Overexpression of
      CRZ1 in the industrial HS13 strain increased both salt and freeze tolerance and
      improved the leavening ability of baker's yeast in high-sugar dough. Moreover,
      engineered cells were able to produce more gas during fermentation of prefrozen
      dough than the parental strain. Similar effects were observed for overexpression
      of TdCRZ1, the homologue to CRZ1 in Torulaspora delbrueckii, suggesting that
      expression of calcineurin-Crz1p target genes can alleviate the harmful effects of
      ionic stress during freezing. However, overexpression of STZ and FTZ, two
      unrelated Arabidopsis thaliana genes encoding Cys(2)/His(2)-type zinc finger
      proteins, also conferred freeze resistance in yeast. Furthermore, experiments
      with Deltacnb1 and Deltacrz1 mutants failed to show a freeze-sensitive phenotype,
      even in cells pretreated with NaCl. Overall, our results demonstrate that
      overexpression of CRZ1 has the potential to be a useful tool for increasing
      freeze tolerance and fermentative capacity in industrial strains. However, these
      effects do not appear to be mediated through activation of known salt-responding
      pathways.

PMID- 17557847
TI  - Sinorhizobium meliloti fur-like (Mur) protein binds a fur box-like sequence
      present in the mntA promoter in a manganese-responsive manner.
AB  - In Sinorhizobium meliloti, the Mur(Sm) protein, a homologue of the ferric uptake
      regulator (Fur), mediates manganese-dependent regulation of the MntABCD manganese
      uptake system. In this study, we analyzed Mur(Sm) binding to the promoter region
      of the S. meliloti mntA gene. We demonstrated that Mur(Sm) protein binds with
      high affinity to the promoter region of mntA gene in a manganese-responsive
      manner. Moreover, the results presented here indicate that two monomers, or one
      dimer, of Mur(Sm) binds the DNA. The binding region was identified by DNase I
      footprinting analysis and covers a region of about 30 bp long that contains a
      palindromic sequence. The Mur(Sm) binding site, present in the mntA promoter
      region, is similar to a Fur box; however, manganese-activated Mur(Sm) binds a
      canonical Fur box with very low affinity. Furthermore, the data obtained indicate
      that Mur(Sm) responds to physiological concentrations of manganese.

PMID- 17557848
TI  - Development of a novel genetic system to create markerless deletion mutants of
      Bdellovibrio bacteriovorus.
AB  - Bdellovibrio bacteriovorus is a species of unique obligate predatory bacteria
      that utilize gram-negative bacteria as prey. Their life cycle alternates between
      a motile extracellular phase and a growth phase within the prey cell periplasm.
      The mechanism of prey cell invasion and the genetic networks and regulation
      during the life cycle have not been elucidated. The obligate predatory nature of
      the B. bacteriovorus life cycle suggests the use of this bacterium in potential
      applications involving pathogen control but adds complexity to the development of
      practical genetic systems that can be used to determine gene function. This work
      reports the development of a genetic technique for allelic exchange or gene
      inactivation by construction of in-frame markerless deletion mutants including
      the use of a counterselectable marker in B. bacteriovorus. A suicide plasmid
      carrying the sacB gene for counterselection was used to inactivate the strB gene
      in B. bacteriovorus HD100 by an in-frame deletion. Despite the inactivation of
      the strB gene, B. bacteriovorus was found to retain resistance to high
      concentrations of streptomycin. The stability of a plasmid for use in
      complementation experiments was also investigated, and it was determined that
      pMMB206 replicates autonomously in B. bacteriovorus. Development of this
      practical genetic system now facilitates the study of B. bacteriovorus at the
      molecular level and will aid in understanding the regulatory networks and gene
      function in this fascinating predatory bacterium.

PMID- 17557849
TI  - Production of lactic acid from cellobiose and cellotriose by Lactobacillus
      delbrueckii mutant Uc-3.
AB  - Lactobacillus delbrueckii mutant Uc-3 utilizes both cellobiose and cellotriose
      efficiently, converting it into L(+) lactic acid. The enzyme activities of
      cellobiose and cellotriose utilization were determined for cell extracts, whole
      cells, and disrupted cells. Aryl-beta-glucosidase activity was detected only for
      whole cells and disrupted cells, suggesting that these activities are cell bound.
      The mutant produced 90 g/liter of lactic acid from 100 g/liter of cellobiose with
      2.25 g/liter/h productivity.

PMID- 17557850
TI  - Evaluation of two library-independent microbial source tracking methods to
      identify sources of fecal contamination in French estuaries.
AB  - In order to identify the origin of the fecal contamination observed in French
      estuaries, two library-independent microbial source tracking (MST) methods were
      selected: (i) Bacteroidales host-specific 16S rRNA gene markers and (ii) F
      specific RNA bacteriophage genotyping. The specificity of the Bacteroidales
      markers was evaluated on human and animal (bovine, pig, sheep, and bird) feces.
      Two human-specific markers (HF183 and HF134), one ruminant-specific marker
      (CF193'), and one pig-specific marker (PF163) showed a high level of specificity
      (>90%). However, the data suggest that the proposed ruminant-specific CF128
      marker would be better described as an animal marker, as it was observed in all
      bovine and sheep feces and 96% of pig feces. F RNA bacteriophages were detected
      in only 21% of individual fecal samples tested, in 60% of pig slurries, but in
      all sewage samples. Most detected F RNA bacteriophages were from genotypes II and
      III in sewage samples and from genotypes I and IV in bovine, pig, and bird feces
      and from pig slurries. Both MST methods were applied to 28 water samples
      collected from three watersheds at different times. Classification of water
      samples as subject to human, animal, or mixed fecal contamination was more
      frequent when using Bacteroidales markers (82.1% of water samples) than by
      bacteriophage genotyping (50%). The ability to classify a water sample increased
      with increasing Escherichia coli or enterococcus concentration. For the samples
      that could be classified by bacteriophage genotyping, 78% agreed with the
      classification obtained from Bacteroidales markers.

PMID- 17557851
TI  - Molecular characterization and evolution of arthropod-pathogenic Rickettsiella
      bacteria.
AB  - We determined the 16S rRNA gene sequences of three crustacean "Rickettsiella
      armadillidii" strains. Rickettsiella bacteria overall appear to form a
      monophyletic group that diverged from Coxiella bacteria approximately 350 million
      years ago. Therefore, the genus Rickettsiella as a whole (not just Rickettsiella
      grylli) should be classified among the Gammaproteobacteria instead of the
      Alphaproteobacteria.

PMID- 17557852
TI  - Responses of wild-type and resistant strains of the hyperthermophilic bacterium
      Thermotoga maritima to chloramphenicol challenge.
AB  - Transcriptomes and growth physiologies of the hyperthermophile Thermotoga
      maritima and an antibiotic-resistant spontaneous mutant were compared prior to
      and following exposure to chloramphenicol. While the wild-type response was
      similar to that of mesophilic bacteria, reduced susceptibility of the mutant was
      attributed to five mutations in 23S rRNA and phenotypic preconditioning to
      chloramphenicol.

PMID- 17557853
TI  - Population dynamics and metabolite target analysis of lactic acid bacteria during
      laboratory fermentations of wheat and spelt sourdoughs.
AB  - Four laboratory sourdough fermentations, initiated with wheat or spelt flour and
      without the addition of a starter culture, were prepared over a period of 10 days
      with daily back-slopping. Samples taken at all refreshment steps were used for
      determination of the present microbiota. Furthermore, an extensive metabolite
      target analysis of more than 100 different compounds was performed through a
      combination of various chromatographic methods including liquid chromatography
      mass spectrometry and gas chromatography-mass spectrometry. The establishment of
      a stable microbial ecosystem occurred through a three-phase evolution within a
      week, as revealed by both microbiological and metabolite analyses. Strains of
      Lactobacillus plantarum, Lactobacillus fermentum, Lactobacillus rossiae,
      Lactobacillus brevis, and Lactobacillus paraplantarum were dominating some of the
      sourdough ecosystems. Although the heterofermentative L. fermentum was dominating
      one of the wheat sourdoughs, all other sourdoughs were dominated by a combination
      of obligate and facultative heterofermentative taxa. Strains of homofermentative
      species were not retrieved in the stable sourdough ecosystems. Concentrations of
      sugar and amino acid metabolites hardly changed during the last days of
      fermentation. Besides lactic acid, ethanol, and mannitol, the production of
      succinic acid, erythritol, and various amino acid metabolites, such as
      phenyllactic acid, hydroxyphenyllactic acid, and indolelactic acid, was shown
      during fermentation. Physiologically, they contributed to the equilibration of
      the redox balance. The biphasic approach of the present study allowed us to map
      some of the interactions taking place during sourdough fermentation and helped us
      to understand the fine-tuned metabolism of lactic acid bacteria, which allows
      them to dominate a food ecosystem.

PMID- 17557854
TI  - Role of type IV pilins in persistence of Vibrio vulnificus in Crassostrea
      virginica oysters.
AB  - Vibrio vulnificus is part of the natural estuarine microflora and accumulates in
      shellfish through filter feeding. It is responsible for the majority of seafood
      associated fatalities in the United States mainly through consumption of raw
      oysters. Previously we have shown that a V. vulnificus mutant unable to express
      PilD, the type IV prepilin peptidase, does not express pili on the surface of the
      bacterium and is defective in adherence to human epithelial cells (R. N.
      Paranjpye, J. C. Lara, J. C. Pepe, C. M. Pepe, and M. S. Strom, Infect. Immun.
      66:5659-5668, 1998). A mutant unable to express one of the type IV pilins, PilA,
      is also defective in adherence to epithelial cells as well as biofilm formation
      on abiotic surfaces (R. N. Paranjpye and M. S. Strom, Infect. Immun. 73:1411
      1422, 2005). In this study we report that the loss of PilD or PilA significantly
      reduces the ability of V. vulnificus to persist in Crassostrea virginica over a
      66-h interval, strongly suggesting that pili expressed by this bacterium play a
      role in colonization or persistence in oysters.

PMID- 17557855
TI  - Involvement of a quorum-sensing-regulated lipase secreted by a clinical isolate
      of Burkholderia glumae in severe disease symptoms in rice.
AB  - Burkholderia glumae is an emerging rice pathogen in several areas around the
      world. Closely related Burkholderia species are important opportunistic human
      pathogens for specific groups of patients, such as patients with cystic fibrosis
      and patients with chronic granulomatous disease. Here we report that the first
      clinical isolate of B. glumae, strain AU6208, has retained its capability to be
      very pathogenic to rice. As previously reported for rice isolate B. glumae BGR1
      (and also for the clinical isolate AU6208), TofI or TofR acyl homoserine lactone
      (AHL) quorum sensing played a pivotal role in rice virulence. We report that AHL
      quorum sensing in B. glumae AU6208 regulates secreted LipA lipase and toxoflavin,
      the phytotoxin produced by B. glumae. B. glumae AU6208 lipA mutants were no
      longer pathogenic to rice, indicating that the lipase is an important virulence
      factor. It was also established that type strain B. glumae ATCC 33617 did not
      produce toxoflavin and lipase and was nonpathogenic to rice. It was determined
      that in strain ATCC 33617 the LuxR family quorum-sensing sensor/regulator TofR
      was inactive. Introducing the tofR gene of B. glumae AU6208 in strain ATCC 33617
      restored its ability to produce toxoflavin and the LipA lipase. This study
      extends the role of AHL quorum sensing in rice pathogenicity through the
      regulation of a lipase which was demonstrated to be a virulence factor. It is the
      first report of a clinical B. glumae isolate retaining strong rice pathogenicity
      and finally determined that B. glumae can undergo phenotypic conversion through a
      spontaneous mutation in the tofR regulator.

PMID- 17557856
TI  - Phylogeography of the thermophilic cyanobacterium Mastigocladus laminosus.
AB  - We have taken a phylogeographic approach to investigate the demographic and
      evolutionary processes that have shaped the geographic patterns of genetic
      diversity for a sample of isolates of the cosmopolitan thermophilic
      cyanobacterial Mastigocladus laminosus morphotype collected from throughout most
      of its range. Although M. laminosus is found in thermal areas throughout the
      world, our observation that populations are typically genetically differentiated
      on local geographic scales suggests the existence of dispersal barriers, a
      conclusion corroborated by evidence for genetic isolation by distance.
      Genealogies inferred using nitrogen metabolism gene sequence data suggest that a
      significant amount of the extant global diversity of M. laminosus can be traced
      back to a common ancestor associated with the western North American hot spot
      currently located below Yellowstone National Park. Estimated intragenic
      recombination rates are comparable to those of pathogenic bacteria known for
      their capacity to exchange DNA, indicating that genetic exchange has played an
      important role in generating novel variation during M. laminosus diversification.
      Selection has constrained protein changes at loci involved in the assimilation of
      both dinitrogen and nitrate, suggesting the historic use of both nitrogen sources
      in this heterocystous cyanobacterium. Lineage-specific differences in thermal
      performance were also observed.

PMID- 17557858
TI  - Probabilistic modeling approach for evaluating the compliance of ready-to-eat
      foods with new European Union safety criteria for Listeria monocytogenes.
AB  - Among the new microbiological criteria that have been incorporated in EU
      Regulation 2073/2005, of particular interest are those concerning Listeria
      monocytogenes in ready-to eat (RTE) foods, because for certain food categories,
      they no longer require zero tolerance but rather specify a maximum allowable
      concentration of 100 CFU/g or ml. This study presents a probabilistic modeling
      approach for evaluating the compliance of RTE sliced meat products with the new
      safety criteria for L. monocytogenes. The approach was based on the combined use
      of (i) growth/no growth boundary models, (ii) kinetic growth models, (iii)
      product characteristics data (pH, a(w), shelf life) collected from 160 meat
      products from the Hellenic retail market, and (iv) storage temperature data
      recorded from 50 retail stores in Greece. This study shows that probabilistic
      analysis of the above components using Monte Carlo simulation, which takes into
      account the variability of factors affecting microbial growth, can lead to a
      realistic estimation of the behavior of L. monocytogenes throughout the food
      supply chain, and the quantitative output generated can be further used by food
      managers as a decision-making tool regarding the design or modification of a
      product's formulation or its "use-by" date in order to ensure its compliance with
      the new safety criteria. The study also argues that compliance of RTE foods with
      the new safety criteria should not be considered a parameter with a discrete and
      binary outcome because it depends on factors such as product characteristics,
      storage temperature, and initial contamination level, which display considerable
      variability even among different packages of the same RTE product. Rather,
      compliance should be expressed and therefore regulated in a more probabilistic
      fashion.

PMID- 17557857
TI  - Impact of three ampicillin dosage regimens on selection of ampicillin resistance
      in Enterobacteriaceae and excretion of blaTEM genes in swine feces.
AB  - The aim of this study was to assess the impact of three ampicillin dosage
      regimens on ampicillin resistance among Enterobacteriaceae recovered from swine
      feces by use of phenotypic and genotypic approaches. Phenotypically, ampicillin
      resistance was determined from the percentage of resistant Enterobacteriaceae and
      MICs of Escherichia coli isolates. The pool of ampicillin resistance genes was
      also monitored by quantification of bla(TEM) genes, which code for the most
      frequently produced beta-lactamases in gram-negative bacteria, using a newly
      developed real-time PCR assay. Ampicillin was administered intramuscularly and
      orally to fed or fasted pigs for 7 days at 20 mg/kg of body weight. The average
      percentage of resistant Enterobacteriaceae before treatment was between 2.5% and
      12%, and bla(TEM) gene quantities were below 10(7) copies/g of feces. By days 4
      and 7, the percentage of resistant Enterobacteriaceae exceeded 50% in all treated
      groups, with some highly resistant strains (MIC of >256 microg/ml). In the
      control group, bla(TEM) gene quantities fluctuated between 10(4) and 10(6)
      copies/g of feces, whereas they fluctuated between 10(6) to 10(8) and 10(7) to
      10(9) copies/g of feces for the intramuscular and oral routes, respectively.
      Whereas phenotypic evaluations did not discriminate among the three ampicillin
      dosage regimens, bla(TEM) gene quantification was able to differentiate between
      the effects of two routes of ampicillin administration. Our results suggest that
      fecal bla(TEM) gene quantification provides a sensitive tool to evaluate the
      impact of ampicillin administration on the selection of ampicillin resistance in
      the digestive microflora and its dissemination in the environment.

PMID- 17557859
TI  - Mycobacterium parascrofulaceum in acidic hot springs in Yellowstone National
      Park.
AB  - Mycobacterium parascrofulaceum was found in Norris Geyser Basin, Yellowstone
      National Park, in a system composed of two acidic (pH 3.0) springs with
      temperatures between 56 degrees C at the source and 40 degrees C at the
      confluence of both springs. Growth and survival assays at 56 degrees C for 60
      days were performed, confirming the origin of the strain.

PMID- 17557860
TI  - Production of recombinant beta-hexosaminidase A, a potential enzyme for
      replacement therapy for Tay-Sachs and Sandhoff diseases, in the methylotrophic
      yeast Ogataea minuta.
AB  - Human beta-hexosaminidase A (HexA) is a heterodimeric glycoprotein composed of
      alpha- and beta-subunits that degrades GM2 gangliosides in lysosomes. GM2
      gangliosidosis is a lysosomal storage disease in which an inherited deficiency of
      HexA causes the accumulation of GM2 gangliosides. In order to prepare a large
      amount of HexA for a treatment based on enzyme replacement therapy (ERT),
      recombinant HexA was produced in the methylotrophic yeast Ogataea minuta instead
      of in mammalian cells, which are commonly used to produce recombinant enzymes for
      ERT. The problem of antigenicity due to differences in N-glycan structures
      between mammalian and yeast glycoproteins was potentially resolved by using alpha
      1,6-mannosyltransferase-deficient (och1Delta) yeast as the host. Genes encoding
      the alpha- and beta-subunits of HexA were integrated into the yeast cell, and the
      heterodimer was expressed together with its isozymes HexS (alphaalpha) and HexB
      (betabeta). A total of 57 mg of beta-hexosaminidase isozymes, of which 13 mg was
      HexA (alphabeta), was produced per liter of medium. HexA was purified with
      immobilized metal affinity column for the His tag attached to the beta-subunit.
      The purified HexA was treated with alpha-mannosidase to expose mannose-6
      phosphate (M6P) residues on the N-glycans. The specific activities of HexA and
      M6P-exposed HexA (M6PHexA) for the artificial substrate 4MU-GlcNAc were 1.2 +/-
      0.1 and 1.7 +/- 0.3 mmol/h/mg, respectively. The sodium dodecyl sulfate
      polyacrylamide gel electrophoresis pattern suggested a C-terminal truncation in
      the beta-subunit of the recombinant protein. M6PHexA was incorporated dose
      dependently into GM2 gangliosidosis patient-derived fibroblasts via M6P receptors
      on the cell surface, and degradation of accumulated GM2 ganglioside was observed.

PMID- 17557861
TI  - Biophysical controls on community succession in stream biofilms.
AB  - Biofilm formation is controlled by an array of coupled physical, chemical, and
      biotic processes. Despite the ecological relevance of microbial biofilms, their
      community formation and succession remain poorly understood. We investigated the
      effect of flow velocity, as the major physical force in stream ecosystems, on
      biofilm community succession (as continuous shifts in community composition) in
      microcosms under laminar, intermediate, and turbulent flow. Flow clearly shaped
      the development of biofilm architecture and community composition, as revealed by
      microscopic investigation, denaturing gradient gel electrophoresis (DGGE)
      analysis, and sequencing. While biofilm growth patterns were undirected under
      laminar flow, they were clearly directed into ridges and conspicuous streamers
      under turbulent flow. A total of 51 biofilm DGGE bands were detected; the average
      number ranged from 13 to 16. Successional trajectories diverged from an initial
      community that was common in all flow treatments and increasingly converged as
      biofilms matured. We suggest that this developmental pattern was primarily driven
      by algae, which, as "ecosystem engineers," modulate their microenvironment to
      create similar architectures and flow conditions in all treatments and thereby
      reduce the physical effect of flow on biofilms. Our results thus suggest a shift
      from a predominantly physical control to coupled biophysical controls on
      bacterial community succession in stream biofilms.

PMID- 17557862
TI  - Staging and classification of testicular tumours: pitfalls from macroscopy to
      diagnosis.
AB  - The accurate assessment of testicular tumours is vital for appropriate treatment
      to be instituted. The assessment begins at specimen receipt, as careful
      macroscopic examination is vital for staging, and this, in part, determines
      whether adjuvant treatment is given. More challenging specimens may include
      partial orchidectomies, biopsies and resection of lymph node or visceral
      metastases. Accurate histological typing is also a potential source of error as
      two classifications are in use, and this may lead to misunderstanding between
      clinician and pathologist. A specialist and multidisciplinary approach is
      advocated. Microscopic staging includes assessment of vascular invasion which may
      be complicated by artifactual spread at the dissecting bench, local invasion,
      assessment of the cord and occasionally lymph node deposits. From careful
      macroscopic examination, to accurate histological typing and reporting of adverse
      pathological parameters, the pathologist plays a major role in the successful
      treatment of a group of rare, but largely treatable, tumours.

PMID- 17557863
TI  - PCR testing for Treponema pallidum in paraffin-embedded skin biopsy specimens:
      test design and impact on the diagnosis of syphilis.
AB  - BACKGROUND: Syphilis, a chronic infection caused by Treponema pallidum, is a
      disease which is increasing in incidence, and thus more and more becoming a
      differential diagnosis in routine pathology. AIMS: To develop a PCR-based
      molecular assay for the detection of T pallidum in formalin-fixed, paraffin
      embedded tissues, and evaluate its diagnostic power, especially in comparison
      with other ancillary methods (immunohistochemistry and Dieterle staining).
      METHODS: 36 skin biopsy specimens with the clinical and/or serological diagnosis
      of syphilis were evaluated by morphology, immunohistochemistry and silver
      staining. A semi-nested PCR assay targeting the T pallidum DNA polymerase A gene
      was designed and applied. Specificity of amplification was confirmed by direct
      sequencing of PCR products. RESULTS: Overall, the presence of T pallidum was
      detected in skin biopsy specimens in 20 cases, by immunohistochemistry, Dieterle
      staining, or PCR. Immunohistochemistry testing was positive in 17/35 cases
      tested, and Dieterle staining in 9/35 cases tested. In comparison, PCR testing
      was positive in 14/36 cases, and highly dependent on the tissue quality. When
      excluding cases with compromised DNA quality, PCR testing was positive in all
      cases except one, including three cases negative by immunohistochemistry and
      Dieterle staining. CONCLUSIONS: PCR testing is significantly more sensitive than
      silver staining, and provided that DNA quality is sufficient, at least as
      sensitive as immunohistochemistry for the detection of T pallidum in formalin
      fixed, paraffin-embedded skin biopsy specimens. Therefore, it is a useful
      ancillary tool in the histological diagnosis of syphilis.

PMID- 17557864
TI  - Renal oncocytoma, yet another tumour that does not fit in the dualistic
      benign/malignant paradigm?

PMID- 17557865
TI  - Involvement of mast cells in gastritis caused by Helicobacter pylori: a potential
      role in epithelial cell apoptosis.
AB  - BACKGROUND: The role(s) of mast cells (MC) in gastric mucosal inflammation caused
      by Helicobacterpylori is (are) still debated. AIM: To determine whether there is
      an association between MC density and epithelial cell apoptosis in antral gastric
      mucosa infected by H pylori. PATIENTS AND METHODS: Biopsy specimens from 122 H
      pylori-positive subjects with chronic active gastritis, 84 patients with non
      steroidal anti-inflammatory drug-induced gastritis and 48 volunteers were
      included. H pylori genotypes were determined by PCR amplification of bacterial
      cultures. Immunohistochemical analysis was performed on tissue microarrays with
      anti-CD117, anti-chymase, anti-tryptase, anti-myeloperoxidase, anti-Bcl-2, anti
      Bcl-x, anti-Bax and anti-caspase 3 antibodies. RESULTS: Of the 122 patients
      infected with H pylori, 76 (62.3%) harboured cagA positive strains. H pylori
      isolates belonged to the vacAs1/m1 genotype in 82 (67%) cases, to the vacAs2/m2
      genotype in 23 (18.8%) cases and to the vacAs1/m2 genotype in 17 (13.9%) cases.
      61 (50%) H pylori isolates were babA2+. In patients infected with H pylori, the
      density of MC, and in particular the number of MC-associated epithelial cells,
      was correlated with a high number of apoptotic epithelial cells. Moreover, the
      density of MC was correlated with the number of neutrophils infiltrating the
      antral gastric mucosa, and was strongly increased in patients infected with cagA,
      vacAs1/m1 and babA2 positive strains. CONCLUSIONS: Taken together, these data
      show that the density of MC can be considered as a histopathological criterion of
      gastritis activity in patients infected with H pylori.

PMID- 17557866
TI  - Indefinite for non-invasive neoplasia lesions in gastric intestinal metaplasia:
      the immunophenotype.
AB  - BACKGROUND: In the Padova International Classification, gastric precancerous
      lesions are labelled as "indefinite for non-invasive neoplasia" (Indef-NiN)
      cytohistological alterations mimicking non-invasive neoplasia (NiN), but lacking
      all the attributes required for a definite NiN categorisation. AIM: To apply a
      panel of immunohistochemical (IHC) markers of cell proliferation (Mib1),
      intestinal differentiation (Cdx2), apoptosis (pro-caspase 3) and cell
      immortalisation (hTERT) to compare the IHC profiles of a series of precancerous
      lesions arising in gastric intestinalised (ie, IM-positive) glands. MATERIALS AND
      METHODS: By applying the histological criteria consistently provided by both the
      Padova Classification and the World Health Organization International Agency, 112
      consecutive cases were considered: intestinal metaplasia (IM; n = 54), Indef-NiN
      in IM-positive gastric glands (n = 28) and low-grade (LG) NiN (n = 30). In each
      histological category, the expression of the marker was separately scored in
      superficial, proliferative and coil compartments. RESULTS: In all glandular
      compartments, Mib1, Cdx2, hTERT and pro-caspase 3 were consistently more
      expressed in LG-NiN than in either IM or Indef-NiN lesions (analysis of variance:
      p<0.001). Significant ORs (calculated by ordinal logistic regression analysis for
      each glandular compartment) associated IM, Indef-NiN and LG-NiN with the
      expression of the considered markers. CONCLUSIONS: A consistent overexpression
      (unrestricted to the proliferative zone) of IHC markers of cell proliferation,
      intestinal differentiation, decreased apoptosis and cell immortalisation
      differentiates LG-NiN from both (simple) IM and Indef-NiN (arising in IM). An
      increased proliferative activity in the proliferative zone discriminates Indef
      NiN lesions (ie, hyperproliferative IM) from IM. Such divergent IHC profiles may
      provide a rationale for scheduling follow-up protocols more properly tailored on
      the patient's risk for cancer.

PMID- 17557867
TI  - The prognostic significance of determining DNA content in breast cancer by DNA
      image cytometry: the role of high grade aneuploidy in node negative breast
      cancer.
AB  - AIM: To investigate the role of DNA aneuploidy, particularly in patients with
      node negative breast cancer, in order to identify the different risk profiles
      within the pool of heterogeneous breast cancers. METHODS: Imprint smears from 370
      breast carcinomas were Feulgen-stained and measured by DNA image analysis. DNA
      aneuploidy was graded by the amount of aneuploid cells (DNA content >5c) and
      highly aneuploid cells (DNA content >9c) in a breast tumour population. These
      results were correlated to the clinical long-term follow-up. A statistical cut
      off value of >10 aneuploid cells (>5c) and of >1 highly aneuploid cell (>9c) was
      evaluated as significant for disease-free survival (DFS) and overall survival
      (OS). RESULTS: Subgroups among patients with breast cancer with aneuploid cells
      below the cut-off value showed a significantly longer DFS and OS than those with
      aneuploid cells above this value. Patients with node negative breast cancer with
      >10 aneuploid cells (>5c) and >1 highly aneuploid cell (>9c) showed an
      unfavourable prognosis similar to patients with node positive breast cancer with
      <10 aneuploid cells (>5c) and <1 highly aneuploid tumour cell (>9c) in DFS and
      OS. CONCLUSION: Nuclear DNA content, as an objective marker of tumour
      aggressiveness, provides prognostic information in patients with both node
      negative and node positive breast cancer. Based on DNA aneuploidy, the clinically
      inhomogeneous group of patients with node negative breast cancer can be
      stratified into low-risk and high-risk subgroups. Therefore, DNA ploidy analysis
      may identify high-risk patients with lymph node negative breast cancer who might
      benefit from additional adjuvant therapy.

PMID- 17557868
TI  - Epigenetic dysregulation of the death-associated protein kinase/p14/HDM2/p53/Apaf
      1 apoptosis pathway in multiple myeloma.
AB  - AIM: To study the role of gene promoter hypermethylation of the putative tumour
      suppressor genes involved in the death-associated protein (DAP)
      kinase/p14/HDM2/p53/Apaf-1 apoptosis pathway in multiple myeloma (MM). METHOD:
      DNAs from 55 primary MM marrow samples and myeloma cell lines were analysed for
      aberrant promoter methylation of DAP kinase, p14 and Apaf-1 genes by methylation
      specific polymerase chain reaction (MSP). RESULT: In the methylated positive
      control, the sensitivity of M-MSP for DAP kinase was 1 x 10(-3). Aberrant
      hypermethylation of DAP kinase was found in 29/55 (52.7%) primary MM samples,
      whereas hypermethylation of p14 or Apaf-1 was undetectable in any of the samples
      tested. 5-Azacytidine treatment of two myeloma cell lines, WL2 and HS-Sultan, led
      to de-methylation and re-expression of DAP kinase, thereby confirming gene
      silencing associated with promoter hypermethylation. Hypermethylation of DAP
      kinase did not correlate with age, sex, paraprotein subtype or Durie-Salmon
      stage, but negatively affected the overall survival. CONCLUSION: Of the putative
      tumour suppressor genes in the DAP kinase/p14/HDM2/p53/Apaf-1 apoptosis pathway,
      only DAP kinase is frequently methylated in MM, which is associated with gene
      silencing and might be of prognostic significance. p14 and Apaf-1 were not
      methylated in MM.

PMID- 17557869
TI  - Specific testing for "isolated" anti-52 kDa SSA/Ro antibodies during standard
      anti-extractable nuclear antigen testing is of limited clinical value.
AB  - AIM: To ascertain whether specific testing for "isolated" anti-52 kDa SSA/Ro
      antibodies (a-SSA/Ro52) during standard anti-extractable nuclear antigen (ENA)
      testing is clinically useful. METHODS: 1438 consecutive sera submitted for anti
      ENA testing over 1 year were evaluated for a-SSA/Ro52 using various assays.
      RESULTS: 7 of 1438 (0.48%) patients were found to have a-SSA/Ro52 without
      SSA/Ro60 antibodies. Subsequent testing detected a further five patients.
      Clinical follow-up was possible in 10/12 patients. 2 of these 10 patients had
      evidence of primary Sjogren's syndrome (SS) and one had systemic lupus
      erythematosus (SLE), with sicca symptoms and abnormal Schirmer's tests. Five
      other patients had sicca symptoms, of which four had abnormal Schirmer's tests.
      CONCLUSIONS: "Isolated" anti-52 kDa SSA/Ro antibodies were detected in
      approximately 0.5% of standard anti-ENA requests, in which their presence was
      generally not associated with underlying SS or SLE. In view of the increased
      testing complexity and costs in detecting and confirming these antibodies,
      specific testing for isolated a-SSA Ro52 antibodies during standard anti-ENA
      testing seems to be of limited clinical value in a non-obstetric population.

PMID- 17557870
TI  - Ewing family of tumours involving the vulva and vagina: report of a series of
      four cases.
AB  - BACKGROUND: Ewing's sarcoma and peripheral primitive neuroectodermal tumour
      (pPNET) are now regarded as two morphological ends of a spectrum of neoplasms,
      characterised by a t(11;22) or other related chromosomal translocation involving
      the EWS gene on chromosome 22 and referred to as Ewing family of tumours (EFTs).
      EFTs are extremely rare in the vulva and vagina, a review of the literature
      revealing only 13 previously reported possible cases, most of which have not had
      molecular confirmation. In this study, four new cases of EFTs involving the vulva
      (three cases) or vagina (one case) are reported. RESULTS: The tumours occurred in
      women aged 19, 20, 30 and 40 years and ranged in size from 3 to 8 cm.
      Morphologically, all neoplasms had a lobulated architecture and were composed of
      solid aggregates of cells. In one case, occasional rosettes were formed. In all
      the tumours, there was diffuse membranous staining with CD99; nuclear positivity
      with FLI-1 was present in two cases. Three cases were focally positive with the
      broad-spectrum cytokeratin AE1/3, all were diffusely positive with vimentin and
      all were desmin negative. In two cases, a t(11;22) (q24;q12) (EWSR1-FLI-1)
      chromosomal translocation was demonstrated by reverse transcriptase-PCR (one
      case) and fluorescence in situ hybridisation (FISH) (one case), and in another
      case a rearrangement of the EWSR1 gene on chromosome 22 was demonstrated by FISH.
      In the other case, a variety of molecular studies did not reveal a translocation
      involving the EWS gene but this tumour, on the balance of probability, is still
      considered to represent a neoplasm in the EFTs. Follow-up in two cases revealed
      that one patient developed pulmonary metastasis and died and another is alive
      without disease at 12 months. CONCLUSIONS: This report expands the published
      literature regarding EFTs involving the vulva and vagina and stresses the
      importance of molecular techniques in firmly establishing the diagnosis,
      especially when these neoplasms arise at unusual sites.

PMID- 17557871
TI  - Microsatellite instability in poorly differentiated adenocarcinomas of the colon
      and rectum: relationship to clinicopathological features.
AB  - BACKGROUND: Poorly differentiated adenocarcinomas of the colon and rectum (Por)
      feature the worst prognosis among the various types of colorectal carcinomas. Por
      is highly associated with microsatellite instability (MSI), although MSI is
      associated with an improved prognosis in colorectal cancers. AIM: To investigate
      the influence of MSI on clinicopathological features and survival of patients
      affected by Por. METHODS: 53 patients affected by Por were investigated. DNA
      extracted from tumour sections and the corresponding normal tissue was analysed
      by PCR at five microsatellite loci: BAT25, BAT26, D2S123, D5S346 and D17S250.
      Tumours with alterations at two or more loci were classified as MSI-Por. The
      others were classified as microsatellite stability (MSS)-Por. The
      clinicopathological features and survival of patients with MSI-Por and MSS-Por
      were investigated. RESULTS: Of the 53 patients who were examined, 12 (22.6%) were
      MSI-Por, whereas 41 (77.4%) were MSS-Por. Significant differences were found
      between MSI-Por and MSS-Por regarding the following clinicopathological features:
      age, gender, lymph-node metastasis (MSI-Por: 4/12; MSS-Por: 33/41), TNM stage
      (MSI-Por: T1/T2/T3/T4 = 2/6/2/2; MSS-Por: 3/3/19/16) and lymphatic invasion (MSI
      Por: 4/10; MSS-Por: 27/35). Kaplan-Meier survival curves and log-rank analysis
      showed that MSI-Por was associated with better prognosis than MSS-Por, although
      no significant difference was found. CONCLUSIONS: Compared with MSS-Por, MSI-Por
      is significantly associated with a low incidence of lymph-node metastases and a
      low stage. This indicates that MSI-Por is a less aggressive subtype.

PMID- 17557872
TI  - Metastatic renal oncocytoma.

PMID- 17557874
TI  - Myelolipoma of the lung: a case report and brief review.

PMID- 17557873
TI  - Plexiform intraneural granular cell tumour of a digital cutaneous sensory nerve.

PMID- 17557875
TI  - Adverse effects of dyes used in sentinel node biopsy on immunocytochemical
      determination of hormone receptors in breast cancer cells.

PMID- 17557876
TI  - Return to sports and recreational activity after unicompartmental knee
      arthroplasty.
AB  - BACKGROUND: There is a lack of detailed information concerning patients' sports
      and recreational activities after unicompartmental knee arthroplasty. HYPOTHESIS:
      Patients treated by unicompartmental knee arthroplasty will be able to return to
      sports and activity. STUDY DESIGN: Case series; Level of evidence, 4. METHODS:
      The authors surveyed 83 patients by postal questionnaires to determine their
      sporting and recreational activities at a mean follow-up of 18 +/- 4.6 months
      (range, 12-28) after unicompartmental knee arthroplasty. For data analysis,
      patients were divided into groups of women and men, and older and younger
      patients (those above and below the median age of the group). The authors also
      assessed the state of general health (SF-36) of the patients at the time of the
      survey and compared the results with those of a matched (for age and side
      diagnoses) reference population. RESULTS: Before surgery, 77 of 83 patients were
      engaged in an average of 5.0 sports and recreational disciplines;
      postoperatively, 73 (88%) participated in an average of 3.1 different sports
      disciplines, resulting in a return to activity rate of 95%. The frequency of
      activities (sessions per week) was 2.9 preoperatively and remained constant at
      the time of survey (2.8). The group of older patients (mean age 73.0 y) revealed
      a significantly higher frequency than the group of younger patients (mean age
      57.8 y). The minimum session length decreased from 66 minutes before surgery to
      55 minutes after surgery. The most common activities after surgery were hiking,
      cycling, and swimming. Several high-impact activities, as well as the winter
      disciplines of downhill- and cross-country skiing had a significant decrease in
      participating patients. The majority of the patients (90.3%) stated that surgery
      had maintained or improved their ability to participate in sports or recreational
      activities. The patients generally scored very high on the SF-36 compared with
      the matched reference population. Higher SF-36 values in the physical-related
      domains correlated with an increased level of activity (r = 0.425). The
      preoperative body mass index showed a weak, negative correlation with the
      postoperative extent of activities (r = -0.282). CONCLUSION: The majority of
      patients returned to sports and recreational activity after unicompartmental knee
      arthroplasty. However, the numbers of different disciplines patients were engaged
      in decreased as well as the extent of activities. The activities in which most
      patients participated were primarily low- or midimpact. The patients scored
      higher on the SF-36 than age-related norms, which might be due to the patient
      selection process for unicompartmental knee arthroplasty and geographical
      differences.

PMID- 17557877
TI  - The value of power Doppler ultrasonography in Achilles tendinopathy: a
      prospective study.
AB  - BACKGROUND: Neovascularization, detected with power Doppler ultrasonography
      (PDU), is thought by some to play a central role in pathogenesis of Achilles
      tendinopathy. HYPOTHESIS: Power Doppler ultrasonography neovascularization score
      is correlated with clinical severity at baseline and after conservative
      treatment. STUDY DESIGN: Cohort study (prognosis); Level of evidence, 2. METHODS:
      Seventy tendons from 58 patients with chronic midportion Achilles tendinopathy
      were included, and 63 symptomatic tendons were analyzed. All patients were
      prescribed a 12-week heavy-load eccentric training program and evaluated with PDU
      at baseline and 12 weeks. Patient satisfaction, Victorian Institute of Sports
      Assessment-Achilles (VISA-A) score, and mean visual analog scale (VAS) score were
      correlated with degree of neovascularization (5-grade scale). RESULTS: Of the 63
      symptomatic tendons, baseline neovascularization scores were 23 grade 0 (37% no
      neovessels), 18 grade 1, 8 grade 2, 8 grade 3, and 6 grade 4 (63%
      neovascularization grades 1-4). At baseline, neovascularization was not
      significantly correlated with the mean VAS score (r=.19, P=.131) and VISA-A score
      (r=-.23, P=.074). At 12-week follow-up, the neovascularization score
      significantly correlated with the mean VAS score (r=.43, P<.001) and VISA-A score
      (r=-.46, P<.001). No significant differences were found in improvement of VISA-A
      score after treatment between patients with neovessels (grades 1-4) or without
      neovessels (grade 0) at baseline. CONCLUSION: Sixty-three percent of the
      symptomatic tendons were found to have neovessels at baseline. There was no
      significant correlation between neovascularization score and clinical severity at
      baseline, but at follow-up, there was a significant correlation.
      Neovascularization at baseline did not predict clinical outcome after
      conservative treatment.

PMID- 17557878
TI  - Coding tandem repeats generate diversity in Aspergillus fumigatus genes.
AB  - Genes containing multiple coding mini- and microsatellite repeats are highly
      dynamic components of genomes. Frequent recombination events within these tandem
      repeats lead to changes in repeat numbers, which in turn alters the amino acid
      sequence of the corresponding protein. In bacteria and yeasts, the expansion of
      such coding repeats in cell wall proteins is associated with alterations in
      immunogenicity, adhesion, and pathogenesis. We hypothesized that identification
      of repeat-containing putative cell wall proteins in the human pathogen
      Aspergillus fumigatus may reveal novel pathogenesis-related elements. Here, we
      report that the genome of A. fumigatus contains as many as 292 genes with
      internal repeats. Fourteen of 30 selected genes showed size variation of their
      repeat-containing regions among 11 clinical A. fumigatus isolates. Four of these
      genes, Afu3g08990, Afu2g05150 (MP-2), Afu4g09600, and Afu6g14090, encode putative
      cell wall proteins containing a leader sequence and a
      glycosylphosphatidylinositol anchor motif. All four genes are expressed and
      produce variable-size mRNA encoding a discrete number of repeat amino acid units.
      Their expression was altered during development and in response to cell wall
      disrupting agents. Deletion of one of these genes, Afu3g08990, resulted in a
      phenotype characterized by rapid conidial germination and reduced adherence to
      extracellular matrix suggestive of an alteration in cell wall characteristics.
      The Afu3g08990 protein was localized to the cell walls of dormant and germinating
      conidia. Our findings suggest that a subset of the A. fumigatus cell surface
      proteins may be hypervariable due to recombination events in their internal
      tandem repeats. This variation may provide the functional diversity in cell
      surface antigens which allows rapid adaptation to the environment and/or elusion
      of the host immune system.

PMID- 17557879
TI  - Unusually low levels of genetic variation among Giardia lamblia isolates.
AB  - Giardia lamblia, an intestinal pathogen of mammals, including humans, is a
      significant cause of diarrheal disease around the world. Additionally, the
      parasite is found on a lineage which separated early from the main branch in
      eukaryotic evolution. The extent of genetic diversity among G. lamblia isolates
      is insufficiently understood, but this knowledge is a prerequisite to better
      understand the role of parasite variation in disease etiology and to examine the
      evolution of mechanisms of genetic exchange among eukaryotes. Intraisolate
      genetic variation in G. lamblia has never been estimated, and previous studies on
      interisolate genetic variation have included a limited sample of loci. Here we
      report a population genetics study of intra- and interisolate genetic diversity
      based on six coding and four noncoding regions from nine G. lamblia isolates. Our
      results indicate exceedingly low levels of genetic variation in two out of three
      G. lamblia groups that infect humans; this variation is sufficient to allow
      identification of isolate-specific markers. Low genetic diversity at both coding
      and noncoding regions, with an overall bias towards synonymous substitutions, was
      discovered. Surprisingly, we found a dichotomous haplotype structure in the
      third, more variable G. lamblia group, represented by a haplotype shared with one
      of the homogenous groups and an additional group-specific haplotype. We propose
      that the distinct patterns of genetic-variation distribution among lineages are a
      consequence of the presence of genetic exchange. More broadly, our findings have
      implications for the regulation of gene expression, as well as the mode of
      reproduction in the parasite.

PMID- 17557880
TI  - Characterization of a novel gene for strain typing reveals substructuring of
      Aspergillus fumigatus across North America.
AB  - Fifty-five epidemiologically linked Aspergillus fumigatus isolates obtained from
      six nosocomial outbreaks of invasive aspergillosis were subtyped by sequencing
      the polymorphic region of the gene encoding a putative cell surface protein,
      Afu3g08990 (denoted as CSP). Comparative sequence analysis showed that genetic
      diversity was generated in the coding region of this gene by both tandem repeats
      and point mutations. Each unique sequence in an outbreak cluster was assigned an
      arbitrary number or CSP sequence type. The CSP typing method was able to identify
      "clonal" and genotypically distinct A. fumigatus isolates, and the results of
      this method were concordant with those of another discriminatory genotyping
      technique, the Afut1 restriction fragment length polymorphism typing method. The
      novel single-locus sequence typing (CSP typing) strategy appears to be a simple,
      rapid, discriminatory tool that can be readily shared across laboratories. In
      addition, we found that A. fumigatus isolates substructured into multiple clades;
      interestingly, one clade consisted of isolates predominantly representing
      invasive clinical isolates recovered from cardiac transplant patients from two
      different outbreak situations. We also found that the A. fumigatus isolate Af293,
      whose genome has been sequenced, possesses a CSP gene structure that is
      substantially different from those of the other A. fumigatus strains studied
      here, highlighting the need for further taxonomic study.

PMID- 17557882
TI  - EnP1, a microsporidian spore wall protein that enables spores to adhere to and
      infect host cells in vitro.
AB  - Microsporidia are spore-forming fungal pathogens that require the intracellular
      environment of host cells for propagation. We have shown that spores of the genus
      Encephalitozoon adhere to host cell surface glycosaminoglycans (GAGs) in vitro
      and that this adherence serves to modulate the infection process. In this study,
      a spore wall protein (EnP1; Encephalitozoon cuniculi ECU01_0820) from E. cuniculi
      and Encephalitozoon intestinalis is found to interact with the host cell surface.
      Analysis of the amino acid sequence reveals multiple heparin-binding motifs,
      which are known to interact with extracellular matrices. Both recombinant EnP1
      protein and purified EnP1 antibody inhibit spore adherence, resulting in
      decreased host cell infection. Furthermore, when the N-terminal heparin-binding
      motif is deleted by site-directed mutagenesis, inhibition of adherence is
      ablated. Our transmission immunoelectron microscopy reveals that EnP1 is embedded
      in the microsporidial endospore and exospore and is found in high abundance in
      the polar sac/anchoring disk region, an area from which the everting polar tube
      is released. Finally, by using a host cell binding assay, EnP1 is shown to bind
      host cell surfaces but not to those that lack surface GAGs. Collectively, these
      data show that given its expression in both the endospore and the exospore, EnP1
      is a microsporidian cell wall protein that may function both in a structural
      capacity and in modulating in vitro host cell adherence and infection.

PMID- 17557881
TI  - Sugar nucleotide pools of Trypanosoma brucei, Trypanosoma cruzi, and Leishmania
      major.
AB  - The cell surface glycoconjugates of trypanosomatid parasites are intimately
      involved in parasite survival, infectivity, and virulence in their insect vectors
      and mammalian hosts. Although there is a considerable body of work describing
      their structure, biosynthesis, and function, little is known about the sugar
      nucleotide pools that fuel their biosynthesis. In order to identify and quantify
      parasite sugar nucleotides, we developed an analytical method based on liquid
      chromatography-electrospray ionization-tandem mass spectrometry using multiple
      reaction monitoring. This method was applied to the bloodstream and procyclic
      forms of Trypanosoma brucei, the epimastigote form of T. cruzi, and the
      promastigote form of Leishmania major. Five sugar nucleotides, GDP-alpha-d
      mannose, UDP-alpha-d-N-acetylglucosamine, UDP-alpha-d-glucose, UDP-alpha
      galactopyranose, and GDP-beta-l-fucose, were common to all three species; one,
      UDP-alpha-d-galactofuranose, was common to T. cruzi and L. major; three, UDP-beta
      l-rhamnopyranose, UDP-alpha-d-xylose, and UDP-alpha-d-glucuronic acid, were found
      only in T. cruzi; and one, GDP-alpha-d-arabinopyranose, was found only in L.
      major. The estimated demands for each monosaccharide suggest that sugar
      nucleotide pools are turned over at very different rates, from seconds to hours.
      The sugar nucleotide survey, together with a review of the literature, was used
      to define the routes to these important metabolites and to annotate relevant
      genes in the trypanosomatid genomes.

PMID- 17557883
TI  - Comparative analysis of alterations in host phenotype and transcript accumulation
      following hypovirus and mycoreovirus infections of the chestnut blight fungus
      Cryphonectria parasitica.
AB  - Infection of the chestnut blight fungus, Cryphonectria parasitica, by hypovirus
      CHV1-EP713 or by reovirus MyRV1-Cp9B21 or MyRV2-CpC18 results in reduced fungal
      virulence (hypovirulence). However, additional phenotypic changes caused by the
      two groups of mycoviruses are quite different. We now report that the loss of
      female fertility and the resulting absence of virus transmission through sexual
      spores observed after hypovirus infection was not observed for reovirus-infected
      C. parasitica. Consistent with this result, expression of two genes involved in
      sexual reproduction, the pheromone precursor gene, Mf2/1, and the yeast STE12
      like transcriptional factor gene, cpst12, was less reduced in reovirus-infected
      strains than in the hypovirus CHV1-EP713-infected strain. Analysis with a custom
      microarray cDNA chip containing expressed sequence tag clones representing
      approximately 2,200 unique C. parasitica genes identified 140 and 128 host genes
      that were responsive to MyRV1-Cp9B21 or MyRV2-CpC18 infection, respectively.
      Comparison of these virus-responsive genes revealed an overlap of 85 genes, even
      though the nucleotide sequence identity for the two reoviruses is less than 50%.
      Significantly, 84 of the 85 genes were altered in the same direction. Further
      comparison revealed that 51% and 48% of the MyRV1-Cp9B21- and MyRV2-CpC18
      responsive genes were also responsive to CHV1-EP713 infection. Finally, similar
      to results reported for CHV1-EP713 infection, a high percentage (59% and 66%) of
      the reovirus-responsive genes were also differentially expressed following
      disruption of the cellular G-protein signal transduction pathway. These data
      support the hypothesis that hypovirus and reovirus infections perturb common and
      specific C. parasitica regulatory pathways to cause hypovirulence and distinct
      sets of phenotypic changes.

PMID- 17557884
TI  - Plasmodium p25 and p28 surface proteins: potential transmission-blocking
      vaccines.

PMID- 17557886
TI  - Compound tests for the detection of hitchhiking under positive selection.
AB  - Many statistical tests have been developed for detecting positive selection. Most
      of these tests draw conclusions based on significant deviations from the patterns
      of polymorphism predicted by the neutral model. However, many non-equilibrium
      forces may cause similar deviations, and thus the tests usually have low
      statistical specificity to positive selection. The main challenge is hence to
      construct test statistics that are reasonably powerful in detecting positive
      selection, but are relatively insensitive to other forces. Recently, Zeng et al.
      (2006) proposed a new test, DH, which is a compound of Tajima's D and Fay and
      Wu's H, and showed that DH has reasonably high statistical specificity to
      positive selection. In this report, we expand the idea of a compound test by
      combining Fay and Wu's H or DH with the Ewens-Watterson (EW) test. We refer to
      these 2 new tests as HEW and DHEW, respectively. Compared to the DH test, HEW and
      DHEW are more robust against the presence of recombination, and are also more
      powerful in detecting positive selection. Furthermore, the DHEW test, similar to
      DH, is also relatively insensitive to background selection and demography. The
      HEW test, on the other hand, tends to be somewhat less conservative than DH and
      DHEW in some cases.

PMID- 17557885
TI  - Proposed carbon dioxide concentrating mechanism in Chlamydomonas reinhardtii.

PMID- 17557887
TI  - Treatment of lupus-prone NZB/NZW F1 mice with recombinant soluble Fc gamma
      receptor II (CD32).
AB  - OBJECTIVES: Systemic lupus erythematosus (SLE) is a classical autoimmune disorder
      characterised by the production of IgG autoantibodies against double-stranded DNA
      (dsDNA). Activation of Fc gamma R-bearing effector cells by immune complexes
      (ICs) is a key event in SLE pathogenesis as lupus-prone NZB/NZW F(1) hybrids
      lacking activating Fc gamma receptors (Fc gamma R) are protected against
      inflammatory kidney damage despite glomerular deposition of ICs. Moreover,
      soluble Fc gamma Rs inhibit IC-caused Arthus reaction in vivo. Therefore,
      recombinant human soluble Fc gamma RII (CD32) was evaluated as a novel
      therapeutic strategy in lupus-like disease in NZB/NZW F(1) hybrids. METHODS:
      Binding of husCD32 to murine IgG was studied in vitro by binding to IgG-coated
      erythrocytes and inhibition of phagocytosis of IgG-opsonised murine erythrocytes.
      In order to examine therapeutic impact of husCD32 in vivo, female NZB/NZW F(1)
      mice were treated either from week 16 to 20 ("prophylactic", 150 microg/week
      husCD32) or continuously from week 24 ("therapeutic"; 100 microg/week husCD32) by
      subcutaneous injections. Controls received buffered saline. RESULTS: In vitro
      investigations of husCD32 revealed binding to murine erythrocytes coated with
      murine IgG. Moreover, husCD32 substantially diminished phagocytosis of murine IgG
      opsonised murine red blood cells by peritoneal macrophages indicating disruption
      of IgG-Fc gamma R interaction. There was a therapeutic efficacy of husCD32 to
      attenuate lupus pathology indicated by significantly delayed onset of proteinuria
      and weight loss, reduced histopathological findings, delayed development of
      anaemia and improved survival by prophylactic application. Therapeutic treatment
      did not reverse nephritis but significantly prolonged survival despite apparent
      kidney damage. B cell count, concentration of IgG anti-dsDNA autoantibodies and
      deposition of glomerular ICs was not significantly affected by the application of
      husCD32. CONCLUSIONS: The results demonstrate binding properties of husCD32 to
      ICs in vitro and as a proof-of-principle therapeutic efficacy in inhibiting
      chronic murine lupus pathology in vivo.

PMID- 17557888
TI  - Inverse relationship between vertebral fractures and spine osteoarthritis in
      postmenopausal women with osteoporosis.
AB  - BACKGROUND: Although the coexistence of osteoarthritis and osteoporosis is
      considered as uncommon, it has been suggested that, in postmenopausal women, disc
      space narrowing increases the risk of vertebral fracture. The aim of this study
      was to check this hypothesis in postmenopausal women with osteoporosis.
      OBJECTIVE: We analysed the relationship between vertebral fractures and spine
      osteoarthritis in 410 postmenopausal women with osteoporosis: in this population
      both disc space narrowing and osteophytes are inversely related to vertebral
      fractures. PATIENTS AND METHODS: This study is based on baseline data collected
      in a multicentre, prospective and 6-month longitudinal observational study. 410
      postmenopausal women (74+/-5 years) were enrolled who had consulted for back
      pain, and had osteoporosis (according to WHO definition). Spine x-rays were
      performed according to standardised procedures. Vertebral fractures were
      evaluated from T4 to L4 using the Genant's semiquantitative method;
      osteoarthritis was evaluated by scoring osteophytes and disc space narrowing at
      all levels of the thoracic and lumbar spine, and by a qualitative assessment of
      facet joint arthritis. RESULTS: The prevalence of vertebral fractures was 52.4%.
      At least one osteophyte, one disc space narrowing and one facet arthritis were
      present in 90.2, 64.6 and 77.8% of patients respectively. There was an inverse
      association between vertebral fractures and osteoarthritis: odds ratios adjusted
      for age and weight (95% CI) were 0.38 (0.17-0.86), p = 0.02 and 0.27 (0.16-0.46),
      p<10(-4) for the presence of at least one osteophyte, and of at least three disc
      space narrowings respectively. In a cluster analysis, it was possible to identify
      a subgroup of patients without any disc space narrowing, and another subgroup
      with all patients having at least one disc space narrowing; the proportion of
      patients having more than three vertebral fractures was 25.2 and 15.9% in these
      two clusters respectively. CONCLUSIONS: Disc space narrowing and osteophytes are
      associated with a decreased vertebral fracture prevalence in postmenopausal women
      with osteoporosis.

PMID- 17557890
TI  - Mortality and risk factors of scleroderma renal crisis: a French retrospective
      study of 50 patients.
AB  - OBJECTIVES: To describe presentation and outcome of patients with scleroderma
      renal crisis (SRC). METHODS: SRC was defined as rapidly progressive oliguric
      renal insufficiency and/or rapidly progressive arterial hypertension occurring
      during the course of systemic sclerosis (SSc). Chronic dialysis-free survival was
      analysed using multivariate Cox proportional hazards regression models. The risk
      for developing SRC associated with corticosteroid (CS) exposure during the
      preceding 1- or 3-month periods was analysed according to a case-crossover
      design. RESULTS: A total of 50 SSc patients aged 53.3 (14.5) (mean (SD)) years
      were included in the study. SRC occurred between 1979 and 2003, after a mean (SD)
      disease duration of 27.7 (49.1) months. A total of 43 (86%) patients had diffuse
      SSc, 5 (10%) had limited cutaneous SSc and 2 (4%) had SSc sine scleroderma. At
      the time of SRC, 10 (20%) patients were taking angiotensin converting enzyme
      inhibitors, and mean creatininaemia was 468 (293) micromol/l. A total of 28 (56%)
      patients required haemodialysis. In all, 11 patients underwent a renal biopsy,
      all of them had specific vascular lesions of SRC. Multivariate analyses retained
      age >53 years and normal blood pressure as independent predictors of decreased
      dialysis-free survival. Exposure to CS prior to SRC was identified in 30 (60%)
      patients. The odds ratios for developing SRC associated with CS exposure during
      the preceding 1- or 3-month periods were 24.1 (95% CI 3.0-193.8) and 17.4 (95% CI
      2.1-144.0), respectively. CONCLUSION: SRC remains associated with severe
      morbidity and mortality. CS might increase the risk of developing SRC. Further
      studies are needed to confirm these results.

PMID- 17557891
TI  - Rheumatoid arthritis is associated with a high prevalence of hypothyroidism that
      amplifies its cardiovascular risk.
AB  - OBJECTIVE: Rheumatoid arthritis (RA) patients have an increased risk of
      developing cardiovascular diseases (CVD). Other autoimmune diseases such as
      hypothyroidism are also associated with an enhanced risk for CVD. Our objective
      was to determine first, the prevalence of hypothyroid disorders in RA patients,
      and second, the risk of CVD in RA patients with hypothyroid abnormalities.
      METHODS:  SUBJECTS: were RA patients who participated in an ongoing prospective
      cohort study of cardiovascular mortality and morbidity (n = 358) in which
      hypothyroid abnormalities were assessed. CVD was defined as a verified medical
      history of coronary, cerebral or peripheral arterial disease. RESULTS: Clinical
      hypothyroidism was observed in 16 of 236 female RA patients (6.8%), which is
      significantly higher than in the general population of The Netherlands.
      Subclinical hypothyroidism was detected in 6 out of 236 RA women (2.5%). In
      female RA patients, CVD was present in 6 out of 16 (37.5%) of all hypothyroid
      women. The odds ratio for CVD comparing female hypothyroid RA patients with
      female euthyroid RA patients was 4.1 (95% CI 1.2-14.3) after adjustment for sex,
      age, diabetes, smoking (ever), hypertension and statin use. CONCLUSIONS: Clinical
      hypothyroidism was observed three times more often in female RA patients than
      females in the general population. In female RA patients, clinical hypothyroidism
      was associated with a fourfold higher risk of CVD in comparison with euthyroid
      female RA patients independently of the traditional risk factors.

PMID- 17557889
TI  - Vitamin D and autoimmunity: new aetiological and therapeutic considerations.
AB  - Vitamin D is frequently prescribed by rheumatologists to prevent and treat
      osteoporosis. Several observations have shown that vitamin D inhibits
      proinflammatory processes by suppressing the enhanced activity of immune cells
      that take part in the autoimmune reaction. Moreover, recent evidence strongly
      suggests that vitamin D supplementation may be therapeutically beneficial,
      particularly for Th1-mediated autoimmune disorders. Some reports imply that
      vitamin D may even be preventive in certain disorders such as multiple sclerosis
      and diabetes type 1. It seems that vitamin D has crossed the boundaries of
      calcium metabolism and has become a significant factor in a number of
      physiological functions, specifically as a biological inhibitor of inflammatory
      hyperactivity.

PMID- 17557892
TI  - First metatarsophalangeal joint aspiration using a 29-gauge needle.
AB  - OBJECTIVES: To asses the clinical feasibility of aspirating symptomatic and
      asymptomatic first metatarsophalangeal (MTP) joints with a 29-gauge needle in
      order to obtain a synovial fluid (SF) sample. METHODS: All consecutive
      aspirations of first MTP joints performed within our department were
      prospectively recorded. The procedure was considered successful if SF volume was
      enough to perform a crystal search. Crystals were identified using a polarised
      light microscope (magnification x400) with a first order red compensator. Pain
      was recorded on a 10-cm visual analogue scale (VAS). RESULTS: Aspirations were
      attempted in 33 first MTP joints in 31 patients. SF was drawn from 30 of the
      joints (91%), with little difference between asymptomatic (89%) and inflamed
      joints (93%). The technique was well tolerated (mean VAS 1.74). Urate monosodium
      crystals were identified in 22 samples (73%) and another sample contained calcium
      pyrophosphate dihydrate crystals. CONCLUSIONS: A 29-gauge needle allows easy
      aspiration of the first MTP joint with only modest discomfort for the patients,
      and generally yields a SF sample of sufficient volume for crystal detection and
      identification.

PMID- 17557893
TI  - Group-directed criticisms and recommendations for change: why newcomers arouse
      more resistance than old-timers.
AB  - Three experiments examine the extent to which newcomers are able to influence
      their groups relative to old-timers. Specifically, how group members respond to
      criticisms of their group was assessed as a function of the intragroup position
      of the speaker. When criticizing their workplace (Experiment 1; N = 116), their
      profession (Experiment 2; N = 106), or an Internet community (Experiment 3; N =
      189), newcomers aroused more resistance than old-timers, an effect that was
      mediated by perceptions of how attached critics were to their group identity.
      Experiment 3 also showed that newcomers could reduce resistance to their
      criticisms by distancing themselves from a group of which they were previously
      members. Theoretical and practical implications of these findings are discussed.

PMID- 17557894
TI  - HIF prolyl hydroxylase inhibition results in endogenous erythropoietin induction,
      erythrocytosis, and modest fetal hemoglobin expression in rhesus macaques.
AB  - The hypoxia-inducible factor (HIF) pathway is crucial in mitigating the
      deleterious effects of oxygen deprivation. HIF-alpha is an essential component of
      the oxygen-sensing mechanisms and under normoxic conditions is targeted for
      degradation via hydroxylation by HIF-prolyl hydroxylases. Several HIF-prolyl
      hydroxylase inhibitors (PHIs) induced erythropoietin (epo) expression in vitro
      and in mice, with peak epo expression ranging from 5.6- to 207-fold above control
      animals. Furthermore, several PHIs induced fetal hemoglobin (HbF) expression in
      primary human erythroid cells in vitro, as determined by flow cytometry. One PHI,
      FG-2216, was further tested in a nonhuman primate model without and with chronic
      phlebotomy. FG-2216 was orally bioavailable and induced significant and
      reversible Epo induction in vivo (82- to 309-fold at 60 mg/kg). Chronic oral
      dosing in male rhesus macaques was well tolerated, significantly increased
      erythropoiesis, and prevented anemia induced by weekly phlebotomy. Furthermore,
      modest increases in HbF-containing red cells and reticulocytes were demonstrated
      by flow cytometry, though significant increases in HbF were not demonstrated by
      high-pressure liquid chromatography (HPLC). HIF PHIs represent a novel class of
      molecules with broad potential clinical application for congenital and acquired
      anemias.

PMID- 17557895
TI  - Screening for leukemia- and clone-specific markers at birth in children with T
      cell precursor ALL suggests a predominantly postnatal origin.
AB  - Childhood T-cell precursor acute lymphoblastic leukemia (TCP ALL) is an
      aggressive disease with a presumably short latency that differs in many biologic
      respects from B-cell precursor (BCP) ALL. We therefore addressed the issue of in
      utero origin of this particular type of leukemia by tracing oncogenic mutations
      and clone-specific molecular markers back to birth. These markers included
      various first- and second-hit genetic alterations (TCRD-LMO2 breakpoint regions,
      n = 2; TAL1 deletions, n = 3; Notch1 mutations, n = 1) and nononcogenic T-cell
      receptor rearrangements (n = 13) that were derived from leukemias of 16 children
      who were 1.5 to 11.2 years old at diagnosis of leukemia. Despite highly sensitive
      polymerase chain reaction (PCR) approaches (1 cell with a specific marker among
      100,000 normal cells), we identified the leukemic clone in the neonatal blood
      spots in only 1 young child. These data suggest that in contrast to BCP ALL most
      TCP ALL cases are initiated after birth.

PMID- 17557896
TI  - Donor-derived DNA in fingernails among recipients of allogeneic hematopoietic
      stem-cell transplants.
AB  - To examine whether donor-derived cells could exist in nonhematopoietic tissues of
      recipients after allogeneic hematopoietic stem-cell transplantation, we examined
      the patterns of the short tandem repeat (STR) of DNA extracted from fingernail
      clippings of recipients so that the contamination of blood cells was excluded.
      All 21 patients reached donor-derived hematopoiesis after transplantation and 20
      of them were in remission of the primary diseases at the time of sampling.
      Compared with the STRs of donor cells, among 9 of 21 patients, DNA extracted from
      fingernail samples showed coexistence of the donor pattern of the STRs, sharing
      from 8.9% to 72.9% of total STR areas. Time from transplantation to sampling was
      from 305 to 2399 days among positive cases. These results demonstrate for the
      first time the existence of stable contribution of donor cells in fingernails
      among recipients of allogeneic hematopoietic stem cells.

PMID- 17557897
TI  - Hypoxic stress underlies defects in erythroblast islands in the Rb-null mouse.
AB  - Definitive erythropoiesis occurs in islands composed of a central macrophage in
      contact with differentiating erythroblasts. Erythroid maturation including
      enucleation can also occur in the absence of macrophages both in vivo and in
      vitro. We reported previously that loss of Rb induces cell-autonomous defects in
      red cell maturation under stress conditions, while other reports have suggested
      that the failure of Rb-null erythroblasts to enucleate is due to defects in
      associated macrophages. Here we show that erythropoietic islands are disrupted by
      hypoxic stress, such as occurs in the Rb-null fetal liver, that Rb(-/-)
      macrophages are competent for erythropoietic island formation in the absence of
      exogenous stress and that enucleation defects persist in Rb-null erythroblasts
      irrespective of macrophage function.

PMID- 17557898
TI  - CD34 facilitates the development of allergic asthma.
AB  - Asthma is a pulmonary inflammatory disease dependent on eosinophil and mast cell
      infiltration into the lung. CD34 is a sialomucin expressed by both of these cell
      types, and we have used CD34(-/-) mice and a standard mouse model of asthma to
      evaluate the importance of CD34 expression on disease development. In comparison
      with wild-type (wt) mice, CD34(-/-) mice exhibited a dramatic reduction in all
      hallmarks of allergic asthma, including lowered airway inflammatory cell
      infiltration, airway hyperresponsiveness, and mast-cell recruitment. Bone marrow
      transplantation experiments confirmed that these defects are due to CD34
      expression by bone marrow-derived cells. This was not, however, due to an
      inability to respond to antigen as, on a per cell basis, wt and CD34(-/-)
      inflammatory cells exhibit identical responses in cytokine production. We found a
      striking reduction in mobility of CD34(-/-) eosinophils in vitro, the major
      component of inflammatory infiltrates, which was consistent with proposed models
      for CD34 as an inhibitor of cell-cell adhesion. In summary, our data suggest that
      CD34 enhances mast-cell and eosinophil invasiveness and that its expression by
      these cells is a prerequisite for development of allergic asthma.

PMID- 17557899
TI  - Work-related factors associated with age at natural menopause in a generation of
      French gainfully employed women.
AB  - This study's purpose was to identify occupational factors that may influence the
      age at natural menopause in a random sample of gainfully employed French women
      born in 1938 (n=1,594). Occupational physicians selected the subjects from their
      files and interviewed them during their annual visits in 1990 and 1995. The
      authors used Kaplan-Meier survival curves to estimate median age at menopause (52
      years) and multiple Cox models to estimate associations among women's
      characteristics, occupational factors, and age at menopause separately within two
      strata distinguished by a self-reported history of depression. Among women
      without such a history, earlier menopause was associated with smoking more than
      10 cigarettes per day in 1990 (p<0.001), a high-strain job (p=0.01) in 1990, and
      difficult schedules before 1990 (p=0.03). Later menopause was associated with
      higher educational status (p=0.003) and repetitive work in 1990 (p=0.005). Among
      women with a history of depression, a later menopause was associated with having
      at least one child (p<0.001) and menarche later than the age of 13 years
      (p=0.004). Earlier menopause was associated with a high job control in 1990
      (p=0.03) and high school education (p<0.01). These results suggest that certain
      physical job stressors may be related to age at menopause.

PMID- 17557900
TI  - Racial differences in serum selenium concentration: analysis of US population
      data from the Third National Health and Nutrition Examination Survey.
AB  - Lower intake of the essential trace element selenium may be a risk factor for
      prostate cancer and other cancers. In the United States, many racial disparities
      in cancer incidence, such as the 61% higher incidence of prostate cancer among
      Blacks relative to Whites, remain unexplained. Using data from a large,
      nationally representative survey, the authors explored Black/White differences in
      serum selenium concentration. Mean serum selenium concentrations, both crude and
      adjusted for known predictors of serum selenium, were determined for 10,779 Black
      and White males and females aged >or=12 years who participated in the Third
      National Health and Nutrition Examination Survey (1988-1994). Crude mean serum
      selenium concentrations were 126.35 ng/ml for Whites and 118.76 ng/ml
      (approximately 6% lower) for Blacks. Adjustment for known serum selenium
      predictors, including a proxy for residence at the county level, reduced the
      racial disparity, although concentrations remained approximately 3% lower in
      Blacks than in Whites of both sexes (p<0.0001). The observation that Blacks had
      lower unadjusted and adjusted serum selenium concentrations relative to Whites is
      intriguing, given the racial disparity in incidence of prostate cancer and other
      cancers.

PMID- 17557902
TI  - Differential effects of glutathione S-transferase pi (GSTP1) haplotypes on cell
      proliferation and apoptosis.
AB  - Expression of the glutathione S-transferase, GSTP1, is associated with phase 1
      detoxification of the products of oxidative stress. Recently, GSTP1 expression
      has been implicated in the regulation of cell proliferation and apoptosis through
      direct interaction with the c-Jun N-terminal kinase, (JNK). GSTP1 is polymorphic
      and allelic variants have been associated with disease susceptibility and
      clinical outcome. However, the influence of GSTP1 alleles on proliferation and
      apoptosis has not been studied previously. To investigate this, we have examined
      the effects of inducible expression of wild-type GSTP1*A and mutant GSTP1*C
      haplotypes on cell proliferation and apoptosis in NIH3T3 fibroblasts. Cells
      expressing GSTP1*A displayed increased doubling times and a delayed G1-S phase
      transition compared with cells expressing GSTP1*C. Both GSTP1*A and GSTP1*C
      haplotypes protected cells from undergoing apoptosis when exposed to oxidative
      stress. However, analysis of JNK status revealed that only GSTP1*C expression led
      to a reduction in JNK activity compared with GSTP1*A-expressing cells and non
      induced cells. We further examined the effect of GSTP1 alleles on colony-forming
      efficiency (CFE) in soft agar following exposure to oxidative stress and found
      that GSTP1*A-expressing clones had increased CFE compared with non-induced and
      GSTP1*C-expressing clones. Our data suggest that GSTP1 alleles have differential
      effects on proliferation and apoptosis; GSTP1*A reduces cellular proliferation
      and protects against apoptosis through a JNK-independent mechanism. In contrast,
      GSTP1*C does not influence cellular proliferation but protects cells from
      apoptosis through JNK-mediated mechanisms.

PMID- 17557901
TI  - Cortical gamma generators suggest abnormal auditory circuitry in early-onset
      psychosis.
AB  - Neurobiological theories of schizophrenia and related psychoses have increasingly
      emphasized impaired neuronal coordination (i.e., dysfunctional connectivity) as
      central to the pathophysiology. Although neuroimaging evidence has mostly
      corroborated these accounts, the basic mechanism(s) of reduced functional
      connectivity remains elusive. In this study, we examine the developmental
      trajectory and underlying mechanism(s) of dysfunctional connectivity by using
      gamma oscillatory power as an index of local and long-range circuit integrity. An
      early-onset psychosis group and a matched cohort of typically developing
      adolescents listened to monaurally presented click-trains, as whole-head
      magnetoencephalography data were acquired. Consistent with previous work, gamma
      band power was significantly higher in right auditory cortices across groups and
      conditions. However, patients exhibited significantly reduced overall gamma power
      relative to controls, and showed a reduced ear-of-stimulation effect indicating
      that ipsi- versus contralateral presentation had less impact on hemispheric
      power. Gamma-frequency oscillations are thought to be dependent on gamma
      aminobutyric acidergic interneuronal networks, thus these patients' impairment in
      generating and/or maintaining such activity may indicate that local circuit
      integrity is at least partially compromised early in the disease process. In
      addition, patients also showed abnormality in long-range networks (i.e., ear-of
      stimulation effects) potentially suggesting that multiple stages along auditory
      pathways contribute to connectivity aberrations found in patients with psychosis.

PMID- 17557903
TI  - Loss of p53 enhances the induction of colitis-associated neoplasia by dextran
      sulfate sodium.
AB  - Loss of p53 function is an early event in colitis-associated neoplasia in humans.
      We assessed the role of p53 in a mouse model of colitis-associated neoplasia.
      Colitis was induced in p53-/-, p53+/- and p53+/+ mice using three or four cycles
      of dextran sulfate sodium (DSS) followed by 120 days of water. Mice were examined
      for incidence, multiplicity and types of neoplastic lesions. Lesions were
      examined for mutations in beta-catenin (exon 3), K-ras (codons 12/13) and p53
      (exons 5-8) by sequencing and for cellular localization of beta-catenin by
      immunohistochemistry. The incidence of neoplastic lesions was 57, 20 and 20% in
      p53-/-, p53+/- and p53+/+ mice, respectively (P = 0.013). p53-/- mice had a
      greater number of total lesions (P < 0.0001), cancers (P = 0.001) and dysplasias
      (P = 0.009) per mouse than either p53+/- or p53+/+ mice. Flat lesions were
      associated with the p53-/- genotype, whereas polypoid lesions were associated
      with the p53+/- and p53+/+ genotypes (P < 0.0001). beta-Catenin mutations were
      present in 75% of lesions of p53+/+ mice and absent in lesions from p53-/- mice
      (P = 0.055). Nuclear expression of beta-catenin was seen only in polypoid lesions
      (91%). No K-ras or p53 mutations were detected. These data indicate that loss of
      p53 enhances the induction of colitis-associated neoplasia, particularly flat
      lesions, and dysregulation of beta-catenin signaling plays an important role in
      the formation of polypoid lesions in this mouse model. As observed in humans, p53
      plays a protective role in colitis-associated neoplasia in the DSS model.

PMID- 17557904
TI  - Evaluation of genetic variation in the double-strand break repair pathway and
      bladder cancer risk.
AB  - The double-strand break DNA repair (DSBR) pathway is implicated in maintaining
      genomic stability and therefore could affect bladder cancer risk. Here we present
      data evaluating 39 single-nucleotide polymorphisms (SNPs) in seven candidate
      genes whose products are involved in DNA break sensing (NBS1, BRCA1 interacting
      genes BRIP1 and ZNF350), non-homologous end-joining (NHEJ) DNA repair (XRCC4) and
      homologous recombination (HR) repair (RAD51, XRCC2 and XRCC3). SNPs for RAD51 and
      XRCC2 covered most of the common variation. Associations with bladder cancer risk
      were evaluated in 1,150 newly diagnosed cases of urinary bladder transitional
      cell carcinomas and 1,149 controls conducted in Spain during 1997-2001. We found
      that the genetic variants evaluated significantly contributed to bladder cancer
      risk (global likelihood ratio test P = 0.01). Subjects with the ZNF350 R501S
      (rs2,278,415) variant allele showed significantly reduced risk compared with
      common homozygote variants, odds ratio (OR) [95% confidence interval (95% CI)]:
      0.76 (0.62-0.93) per variant allele. Carriers of a putative functional SNP in
      intron 7 of XRCC4 (rs1,805,377) had significantly increased bladder cancer risk
      compared with common homozygotes: 1.33 (1.08-1.64) per variant allele. Lastly,
      XRCC2 homozygote variants for three promoter SNPs (rs10,234,749, rs6,464,268,
      rs3,218,373) and one non-synonymous SNP (rs3,218,536, R188H) were associated with
      reduced bladder cancer risk (ORs ranging from 0.36 to 0.50 compared with common
      homozygotes). Meta-analysis for XRCC3 T241M (rs861,539) had a significant small
      increase in risk among homozygote variants: OR (95% CI) = 1.17 (1.00-1.36).
      Results from this study provide evidence for associations between variants in
      genes in the DSBR pathway and bladder cancers risk that warrant replication in
      other study populations.

PMID- 17557905
TI  - Caffeic acid and its synthetic derivative CADPE suppress tumor angiogenesis by
      blocking STAT3-mediated VEGF expression in human renal carcinoma cells.
AB  - Tumor angiogenesis is required for tumor development and is stimulated by
      angiogenic inducers like VEGF (vascular endothelial growth factor). Our previous
      study demonstrated that STAT3 (signal transducer and activator of transcription
      3) up-regulates HIF-1alpha (hypoxia inducible factor-1alpha) protein stability
      and enhances HIF-1-mediated VEGF expression in hypoxic solid tumor cells, thus
      suggesting that the inhibition of STAT3 signaling may have clinical applications.
      In this study, we examined in vitro and in vivo, whether caffeic acid (CA) or its
      derivative CADPE [3-(3,4-dihydroxy-phenyl)-acrylic acid 2-(3,4-dihydroxy-phenyl)
      ethyl ester] exert anticancer activity by targeting STAT3. It was found that CA
      or CADPE significantly inhibit STAT3 activity, and that this in turn down
      regulates HIF-1alpha activity. Consequently, sequential blockade of STAT3 and HIF
      1alpha resulted in the down-regulation of VEGF by inhibiting their recruitment to
      the VEGF promoter. In mice bearing a Caki-I carcinoma, both CA and CADPE retarded
      tumor growth and suppressed STAT3 phosphorylation, HIF-1alpha expression,
      vascularization and STAT3-inducible VEGF gene expression in tumors. Taken
      together, our results demonstrate that CA and CADPE are potential inhibitors of
      STAT3 and that they suppress tumor angiogenesis by inhibiting the activity of
      STAT3, the expression of HIF-1alpha and VEGF.

PMID- 17557906
TI  - A gene expression biomarker provides early prediction and mechanistic assessment
      of hepatic tumor induction by nongenotoxic chemicals.
AB  - There are currently no accurate and well-validated short-term tests to identify
      nongenotoxic hepatic tumorigens, thus necessitating an expensive 2-year rodent
      bioassay before a risk assessment can begin. Using hepatic gene expression data
      from rats treated for 5 days with one of 100 structurally and mechanistically
      diverse nongenotoxic hepatocarcinogens and nonhepatocarcinogens, a novel
      multigenebiomarker (i.e., signature) was derived to predict the likelihood of
      nongenotoxic chemicals to induce liver tumors in longer term studies. Independent
      validation of the signature on 47 test chemicals indicates an assay sensitivity
      and specificity of 86% and 81%, respectively. Alternate short-term in vivo
      pathological and genomic biomarkers were evaluated in parallel for comparison,
      including liver weight, hepatocellular hypertrophy, hepatic necrosis, serum
      alanine aminotransferase activity, induction of cytochrome P450 genes, and
      repression of Tsc-22 or alpha2-macroglobulin messenger RNA. In contrast to these
      biomarkers, the gene expression-based signature was more accurate. Unlike
      existing tests, an understanding of potential modes of action for hepatic
      tumorigenicity can be derived by comparison of the signature profile of test
      chemicals to hepatic tumorigens of known mechanism, including regenerative
      proliferation, proliferation associated with xenobiotic receptor activation,
      peroxisome proliferation, and steroid hormone-mediated mechanisms. This signature
      is not only more accurate than current methods, but also facilitates the
      identification of mode of action to aid in the early assessment of human cancer
      risk.

PMID- 17557907
TI  - Membrane-coated fiber array approach for predicting skin permeability of chemical
      mixtures from different vehicles.
AB  - A membrane-coated fiber (MCF) array approach was developed for quantitative
      assessment of skin absorption from chemical mixtures, which was based on the
      similarity in the absorption mechanisms of the MCF membrane and the stratum
      corneum of the skin. A set of probe compounds were used to detect the relative
      molecular interaction strengths of chemicals with the vehicle and the membranes,
      which provided a linkage between the skin permeability (log k) and MCF partition
      coefficients (log KF). A predictive model was established via multiple linear
      regression analysis of the data matrix of experimentally measured log k value and
      log KFm values; log k=a0+a1 log KF1+a2 log KF2+...+an log KFm, where m is the
      number of diverse MCFs. Twenty-five probe compounds and three MCFs
      (polydimethylsiloxane for lipophilic, polyacrylate for polarizable, and CarboWax
      for polar interactions) were used to demonstrate the model development processes
      in the MCF array approach. The skin permeability of the probe compounds was
      measured with conventional diffusion cell experiments using dermatomed porcine
      skin. Three predictive models were established for skin permeability prediction
      from chemical mixtures in water, 50% ethanol, and 1% sodium lauryl sulfate (SLS)
      with R2 values of 93, 91, and 83, respectively. The log k and log KF values were
      considerably altered by the addition of ethanol or SLS into the dose vehicle;
      however, their correlations to skin permeability remained strong under various
      conditions. These results suggested that the experimentally based MCF array
      approach can be used to predict skin absorption from chemical mixtures in
      different vehicles or formulations.

PMID- 17557908
TI  - Mouse liver effects of cyproconazole, a triazole fungicide: role of the
      constitutive androstane receptor.
AB  - Cyproconazole, a triazole fungicide, causes hepatocellular adenomas and
      carcinomas in CD-1 mice at dose levels of 100 and 200 ppm. The constitutive
      androstane receptor (CAR) has been shown to play a significant role in the
      overall mode of action for several nongenotoxic rodent carcinogens such as
      phenobarbital. The liver effects of dietary cyproconazole or phenobarbital were
      investigated after 2, 7, or 14 days in male CD-1, C57BL/6J, and C3H/HeNClrBR
      mice. Cyproconazole produced similar, dose-responsive effects in all three
      strains of mice, and the response was similar to that of phenobarbital.
      Subsequently, Car-null and wild-type male mice on a C3H/HeNClrBR background were
      administered 200 or 450 ppm cyproconazole, or 850 ppm phenobarbital for up to 7
      days. In wild-type mice, 200 ppm cyproconazole caused liver hypertrophy,
      increased liver weight and cell proliferation, single-cell necrosis and fat
      vacuolation, effects generally similar to those caused by 850 ppm phenobarbital.
      Plasma cholesterol was decreased by both compounds, but cyproconazole had a
      greater effect. The higher dose (450 ppm) of cyproconazole caused similar
      changes, but greater evidence of liver damage was observed, including a large
      increase in plasma transaminases. Induction of CAR target genes Cyp2b10 and
      Gadd45beta was observed with both compounds, whereas the cell cycle regulatory
      gene Mdm2 was unaffected. In Car-null mice, the effects noted with either
      cyproconazole or phenobarbital were absent or greatly diminished. These
      experiments demonstrate that short-term liver effects of cyproconazole in mice
      are CAR-dependent and similar to those of phenobarbital, a known nongenotoxic
      rodent liver carcinogen.

PMID- 17557909
TI  - Estrogenic effects in the immature rat uterus after dietary exposure to
      ethinylestradiol and zearalenone using a systems biology approach.
AB  - Residues of illegally used hormones are regularly detected in animal products,
      feed, or cocktails recovered at farms. In order to better understand the effects
      of dietary exposure to ethinyl estradiol (EE2, 0.03-1 microg/kg body weight [bw])
      and zearalenone (ZEA, 0.03-1 mg/kg bw), an immature rat uterotrophic assay was
      performed and effects were studied at morphological, histological, and gene
      expression levels. Ligand-mediated coregulator recruitment by estrogen receptor
      alpha (ERalpha) was studied in vitro. Uterine weight and epithelial cell height
      were increased dose dependently after a 3-day oral exposure of rats to the
      highest tested doses of EE2 or ZEA, respectively. At low doses 0.03 microg/kg EE2
      and 0.1 mg/kg ZEA, edema, and vacuolization could already be observed in some
      animals. Exposure to 1 mg/kg ZEA resulted in severe damage of the uterine
      epithelial layer. Our study suggests similar coregulator recruitment and gene
      expression patterns for the two estrogenic compounds. Main regulated pathways
      were remodeling of extracellular matrix, alternative complement activation, cell
      proliferation, and estrogen-mediated calcium signaling. The level of regulation
      differed between EE2 and ZEA, attributing a much lower estrogenic potency to ZEA
      than to EE2. A major difference was their ability to recruit coregulator
      inhibitor of kappa B beta and induce expression of the matrix metalloproteinase 7
      gene (381.4- and 6.9-fold upregulation by EE2 and ZEA, respectively), which plays
      an important role in the maintenance of the integrity of the epithelial layer of
      the uterus during proliferation and growth. This observation may explain the
      observed differences at the histological level.

PMID- 17557910
TI  - Tumor necrosis factor-alpha modulates effects of aryl hydrocarbon receptor
      ligands on cell proliferation and expression of cytochrome P450 enzymes in rat
      liver "stem-like" cells.
AB  - Various liver diseases lead to an extensive inflammatory response and release of
      a number of proinflammatory cytokines, such as tumor necrosis factor-alpha (TNF
      alpha). This cytokine is known to play a major role in liver regeneration as well
      as in carcinogenesis. We investigated possible interactions of TNF-alpha with
      ligands of the aryl hydrocarbon receptor (AhR) and known liver carcinogens, such
      as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and coplanar 3,3',4,4',5
      pentachlorobiphenyl (PCB 126). These compounds have been previously found to
      disrupt cell cycle control in contact-inhibited rat liver WB-F344 cells, an in
      vitro model of adult liver progenitor cells. TNF-alpha itself had no significant
      effect on the proliferation/apoptosis ratio in the WB-F344 cell line. However, it
      significantly potentiated proliferative effects of low picomolar range doses of
      both TCDD and PCB 126, leading to an increase in cell numbers, as well as an
      increased percentage of cells entering the S-phase of the cell cycle. The
      combination of TNF-alpha with low concentrations of AhR ligands increased both
      messenger RNA (mRNA) and protein levels of cyclin A, a principle cyclin involved
      in disruption of contact inhibition. TNF-alpha temporarily inhibited AhR
      dependent induction of cytochrome P450 1A1 (CYP1A1). In contrast, TNF-alpha
      significantly enhanced induction of CYP1B1 at both mRNA and protein levels, by a
      mechanism, which was independent of nuclear factor-kappaB activation. These
      results suggest that TNF-alpha can significantly amplify effects of AhR ligands
      on deregulation of cell proliferation control, as well as on expression of
      CYP1B1, which is involved in metabolic activation of a number of mutagenic
      compounds.

PMID- 17557911
TI  - Inhibition of mitochondrial permeability transition improves functional recovery
      and reduces mortality following acute myocardial infarction in mice.
AB  - Inhibition of mitochondrial permeability transition pore (mPTP) opening by
      cyclosporin A or ischemic postconditioning attenuates lethal reperfusion injury.
      Its impact on major post-myocardial infarction events, including worsening of
      left ventricular (LV) function and death, remains unknown. We sought to determine
      whether pharmacological or postconditioning-induced inhibition of mPTP opening
      might improve functional recovery and survival following myocardial infarction in
      mice. Anesthetized mice underwent 25 min of ischemia and 24 h (protocol 1) or 30
      days (protocol 2) of reperfusion. At reperfusion, they received no intervention
      (control), postconditioning (3 cycles of 1 min ischemia-1 min reperfusion), or
      intravenous injection of the mPTP inhibitor Debio-025 (10 mg/kg). At 24 h of
      reperfusion, mitochondria were isolated from the region at risk for assessment of
      the Ca(2+) retention capacity (CRC). Infarct size was measured by
      triphenyltetrazolium chloride staining. At 30 days of reperfusion, mortality and
      LV contractile function (echocardiography) were evaluated. Postconditioning and
      Debio-025 significantly improved Ca(2+) retention capacity (132 +/- 13 and 153 +/
      31 vs. 53 +/- 16 nmol Ca(2+)/mg protein in control) and reduced infarct size to
      35 +/- 4 and 32 +/- 7% of area at risk vs. 61 +/- 6% in control (P < 0.05). At 30
      days, ejection fraction averaged 74 +/- 6 and 77 +/- 6% in postconditioned and
      Debio-025 groups, respectively, vs. 62 +/- 12% in the control group (P < 0.05).
      At 30 days, survival was improved from 58% in the control group to 92 and 89% in
      postconditioned and Debio-025 groups, respectively. Inhibition of mitochondrial
      permeability transition at reperfusion improves functional recovery and mortality
      in mice.

PMID- 17557912
TI  - Validity of a patient-derived system of tissue-specific human endothelial cells:
      interleukin-6 as a surrogate marker in the coronary system.
AB  - The aim of our study was to evaluate the relevance of tissue- and species
      specific endothelial cells (EC) to study EC-dependent mechanisms in inflammatory
      mediated tissue injury. We established an isolation protocol for highly purified
      EC (pEC) preparations of different origin and compared EC-specific inflammatory
      responses. Fluorescence-activated cell separation was used to obtain pEC cultures
      from different human arterial (coronary artery, internal thoracic artery) and
      venous (umbilical vein, saphenous vein) vessels. All pEC were analyzed for growth
      kinetics, morphology, release of cytokines/chemokines, and expression of E
      selectin. For all different EC cultures, purities of >or=99% were reproducibly
      achieved. The EC isolation did not affect EC growth, morphology, and function.
      However, characterization of pEC from different vessel materials revealed an
      intrinsic, tissue-specific functional heterogeneity of EC cultures. Despite an
      arterial and venous difference in the secretion of IL-8 and monocyte
      chemoattractant protein-1, especially EC from coronary arteries produced
      significantly more IL-6 compared with other EC types, independent of age, gender,
      and disease of the cell donors. In contrast, the expression of E-selectin was not
      affected. We conclude that the proposed isolation protocol allows the generation
      of a pEC bank, enabling us to study tissue-specific aspects at the level of the
      endothelium.

PMID- 17557913
TI  - Endocannabinoids acting at CB1 receptors mediate the cardiac contractile
      dysfunction in vivo in cirrhotic rats.
AB  - Advanced liver cirrhosis is associated with hyperdynamic circulation consisting
      of systemic hypotension, decreased peripheral resistance, and cardiac
      dysfunction, termed cirrhotic cardiomyopathy. Previous studies have revealed the
      role of endocannabinoids and vascular CB(1) receptors in the development of
      generalized hypotension and mesenteric vasodilation in animal models of liver
      cirrhosis, and CB(1) receptors have also been implicated in the decreased beta
      adrenergic responsiveness of isolated heart tissue from cirrhotic rats. Here we
      document the cardiac contractile dysfunction in vivo in liver cirrhosis and
      explore the role of the endocannabinoid system in its development. Rats with
      CCl(4)-induced cirrhosis developed decreased cardiac contractility, as documented
      through the use of the Millar pressure-volume microcatheter system, low blood
      pressure, and tachycardia. Bolus intravenous injection of the CB(1) antagonist
      AM251 (3 mg/kg) acutely increased mean blood pressure, as well as both load
      dependent and -independent indexes of systolic function, whereas no such changes
      were elicited by AM251 in control rats. Furthermore, tissue levels of the
      endocannabinoid anandamide increased 2.7-fold in the heart of cirrhotic compared
      with control rats, without any change in 2-arachidonoylglycerol levels, whereas,
      in the cirrhotic liver, both 2-arachidonoylglycerol (6-fold) and anandamide (3.5
      fold) were markedly increased. CB(1)-receptor expression in the heart was
      unaffected by cirrhosis, as verified by Western blotting. Activation of cardiac
      CB(1) receptors by endogenous anandamide contributes to the reduced cardiac
      contractility in liver cirrhosis, and CB(1)-receptor antagonists may be used to
      improve contractile function in cirrhotic cardiomyopathy and, possibly, in other
      forms of heart failure.

PMID- 17557914
TI  - Heparin-binding EGF-like growth factor mediates oxyhemoglobin-induced suppression
      of voltage-dependent potassium channels in rabbit cerebral artery myocytes.
AB  - Oxyhemoglobin (OxyHb) can suppress voltage-dependent K(+) channel (K(V)) currents
      through protein tyrosine kinase activation, which may contribute to cerebral
      vasospasm following subarachnoid hemorrhage. Here we have tested the hypothesis
      that shedding of heparin-binding EGF-like growth factor (HB-EGF) and the
      resulting activation of the tyrosine kinase EGF receptor (EGFR) underlie OxyHb
      induced K(V) channel suppression in the cerebral vasculature. With the use of the
      conventional whole cell patch-clamp technique, two EGFR ligands, EGF and HB-EGF,
      were found to mimic OxyHb-induced K(V) suppression in rabbit cerebral artery
      myocytes. K(V) current suppression by OxyHb or EGF ligands was eliminated by a
      specific EGFR inhibitor, AG-1478, but was unaffected by PKC inhibition. Compounds
      (heparin and CRM-197) that specifically interfere with HB-EGF signaling
      eliminated OxyHb-induced K(V) suppression, suggesting that HB-EGF is the EGFR
      ligand involved in this pathway. HB-EGF exists as a precursor protein that, when
      cleaved by matrix metalloproteases (MMPs), causes EGFR activation. MMP activation
      was detected in OxyHb-treated arteries by gelatin zymography. Furthermore, the
      MMP inhibitor (GM-6001) abolished OxyHb-induced K(V) current suppression. We also
      observed K(V) current suppression due to EGFR activation in human cerebral artery
      myocytes. In conclusion, these data demonstrate that OxyHb induces MMP
      activation, causing HB-EGF shedding and enhanced EGFR activity, ultimately
      leading to K(V) channel suppression. We propose that EGFR-mediated K(V)
      suppression contributes to vascular pathologies, such as cerebral vasospasm, and
      may play a more widespread role in the regulation of regional blood flow and
      peripheral resistance.

PMID- 17557915
TI  - Aging enhances pressure-induced arterial superoxide formation.
AB  - The purpose of this study was to investigate the mechanisms that regulate
      superoxide (O(2)(*-)) production as a function of an acute elevation of
      intravascular pressure and age. Mesenteric arteries isolated from young (6 mo)
      and aged (24 mo) male Fischer 344 rats were used. O(2)(*-) production in vessels
      in response to 80 (normal pressure, NP) and 180 (high pressure, HP) mmHg was
      determined by the superoxide dismutase-inhibitable nitroblue tetrazolium (NBT)
      reduction assay. In vessels exposed to NP, O(2)(*-) production was significantly
      higher in aged than in young vessels (32.7 +/- 7.0 vs. 15.4 +/- 2.4 nmol.mg(
      1).30 min(-1)). HP enhanced O(2)(*-) production in vessels of both groups, but
      the enhancement was significantly greater in aged than in young vessels (63.4 +/-
      6.7 vs. 32.7 +/- 4.3 nmol.mg(-1).30 min(-1)). Apocynin (100 micromol/l)
      attenuated HP-induced increases in O(2)(*-) production in both groups, whereas
      allopurinol (100 micromol/l) and N(omega)-nitro-L-arginine methyl ester (100
      mumol/l) inhibited the response only in aged vessels. Confocal microscopy showed
      increases in O(2)(*-) in response to HP in endothelial and smooth muscle layers
      of both groups, with much greater fluorescent staining in aged than in young rats
      and in the endothelium than in smooth muscle cells. No significant changes in
      NAD(P)H oxidase gene and protein expressions were observed in vessels of the two
      groups. Upregulation of protein expression of xanthine oxidase was detected in
      aged vessels. We conclude that NAD(P)H oxidase contributes importantly to HP
      induced enhanced O(2)(*-) production in vessels of both young and aged rats,
      whereas xanthine oxidase and nitric oxide synthase-dependent O(2)(*-) production
      also contribute to the enhancement in mesenteric arteries of aged rats.

PMID- 17557916
TI  - Protective effect of long-term angiotensin II inhibition.
AB  - Experimental studies indicate that angiotensin II (ANG II) through its type 1
      receptor (AT(1)) promotes cardiovascular hypertrophy and fibrosis. Therefore, the
      aim of this study was to analyze whether chronic long-term inhibition of the
      renin-angiotensin system (RAS) can prevent most of the deleterious effects due to
      aging in the cardiovascular system of the normal rat. The main objective was to
      compare two strategies of ANG II blockade: a converting enzyme inhibitor (CEI)
      and an AT(1) receptor blocker (AT(1)RB). A control group remained untreated;
      treatment was initiated 2 wk after weaning. A CEI, enalapril (10 mg.kg(-1).day(
      1)), or an AT(1)RB, losartan (30 mg.kg(-1).day(-1)), was used to inhibit the RAS.
      Systolic blood pressure, body weight, and water and food intake were recorded
      over the whole experimental period. Heart, aorta, and mesenteric artery weight as
      well as histological analysis of cardiovascular structure were performed at 6 and
      18 mo. Twenty animals in each of the three experimental groups were allowed to
      die spontaneously. The results demonstrated a significant protective effect on
      the function and structure of the cardiovascular system in all treated animals.
      Changes observed at 18 mo of age in the hearts and aortas were quite significant,
      but each treatment completely abolished this deterioration. The similarity
      between the results detected with either enalapril or losartan treatment clearly
      indicates that most of the effects are exerted through AT(1) receptors. An
      outstanding finding was the significant and similar prolongation of life span in
      both groups of treated animals compared with untreated control animals.

PMID- 17557917
TI  - Elucidation of the temporal relationship between endothelial-derived NO and EDHF
      in mesenteric vessels.
AB  - Although the endothelium co-generates both nitric oxide (NO) and endothelium
      derived hyperpolarizing factor (EDHF), the relative contribution from each
      vasodilator is not clear. In studies where the endothelium is stimulated acutely,
      EDHF responses predominate in small arteries. However, the temporal relationship
      between endothelial-derived NO and EDHF over more prolonged periods is unclear
      but of major physiological importance. Here we have used a classical
      pharmacological approach to show that EDHF is released transiently compared with
      NO. Acetylcholine (3 x 10(-6) mol/l) dilated second- and/or third-order
      mesenteric arteries for prolonged periods of up to 1 h, an effect that was
      reversed fully and immediately by the subsequent addition of L-NAME (10(-3)
      mol/l) but not TRAM-34 (10(-6) mol/l) plus apamin (5 x 10(-7) mol/l). When
      vessels were pretreated with L-NAME, acetylcholine induced relatively transient
      dilator responses (declining over approximately 5 min), and vessels were
      sensitive to TRAM-34 plus apamin. When measured in parallel, the dilator effects
      of acetylcholine outlasted the smooth muscle hyperpolarization. However, in the
      presence of L-NAME, vasodilatation and hyperpolarization followed an identical
      time course. In vessels from NOSIII(-/-) mice, acetylcholine induced small but
      detectable dilator responses that were transient in duration and blocked by TRAM
      34 plus apamin. EDHF responses in these mouse arteries were inhibited by an
      intracellular calcium blocker, TMB-8, and the phospholipase A(2) inhibitor
      AACOCF(3), suggesting a role for lipid metabolites. These data show for the first
      time that EDHF is released transiently, whereas endothelial-derived NO is
      released in a sustained manner.

PMID- 17557918
TI  - Effect of chronic IL-6 infusion on acute pressor responses to vasoconstrictors in
      mice.
AB  - Interleukin (IL)-6 has been implicated as a contributing factor in the
      pathogenesis of hypertension, although the mechanisms involved are unclear.
      Studies conducted in vitro suggest that IL-6 may have a direct effect on vascular
      tone and may modulate constrictor responses to agonists. Whether this effect can
      be observed in vivo is unknown. Therefore, mice were treated with either IL-6 (16
      ng/h sc) or vehicle for 14 days, and the acute blood pressure and heart rate
      responses to endothelin (ET)-1, angiotensin II (ANG II), and phenylephrine (PE)
      were assessed under isoflurane anesthesia. Blood pressure responses to ET-1 were
      identical in vehicle- and IL-6-infused mice, both in the presence and the absence
      of ganglion blockade with chlorisondamine. The fall in heart rate during ET-1
      responses was significantly attenuated in IL-6-infused mice with autonomic
      reflexes intact (vehicle vs. IL-6, P < 0.05 at 1 and 3 nmol/kg of ET-1), but this
      difference was not observed after ganglionic blockade. Both blood pressure and
      heart rate responses to ANG II were indistinguishable between IL-6- and vehicle
      infused mice, as were responses to PE except for a significant increase in the
      blood pressure response and decrease in the heart rate response in IL-6-infused
      mice observed only at the highest dose of PE (300 microg/kg; P < 0.05). These
      findings show that, despite what might be predicted from studies conducted in
      vitro, chronic exposure to elevated plasma IL-6 concentrations in itself does not
      predispose the mouse to enhanced responsiveness to vasoconstrictors in vivo.

PMID- 17557919
TI  - Exercise training and beta-blocker treatment ameliorate age-dependent impairment
      of beta-adrenergic receptor signaling and enhance cardiac responsiveness to
      adrenergic stimulation.
AB  - Cardiac beta-adrenergic receptor (beta-AR) signaling and left ventricular (LV)
      responses to beta-AR stimulation are impaired with aging. It is shown that
      exercise and beta-AR blockade have a favorable effect on cardiac and vascular
      beta-AR signaling in several cardiovascular diseases. In the present study, we
      examined the effects of these two different strategies on beta-AR dysregulation
      and LV inotropic reserve in the aging heart. Forty male Wistar-Kyoto aged rats
      were randomized to sedentary, exercise (12 wk treadmill training), metoprolol
      (250 mg.kg(-1).day(-1) for 4 wk), and exercise plus metoprolol treatment
      protocols. Ten male Wistar-Kyoto sedentary young rats were also used as a control
      group. Old trained, old metoprolol-treated, and old trained plus metoprolol
      treated rats showed significantly improved LV maximal and minimal first
      derivative of the pressure rise responses to beta-AR stimulation (isoproterenol)
      compared with old untrained animals. We found a significant reduction in cardiac
      sarcolemmal membrane beta-AR density and adenylyl cyclase activity in old
      untrained animals compared with young controls. Exercise training and metoprolol,
      alone or combined, restored cardiac beta-AR density and G-protein-dependent
      adenylyl cyclase activation in old rats. Although cardiac membrane G-protein
      receptor kinase 2 levels were not upregulated in untrained old compared with
      young control rats, both exercise and metoprolol treatment resulted in a dramatic
      reduction of G-protein-receptor kinase 2 protein levels, which is a further
      indication of beta-AR signaling amelioration in the aged heart induced by these
      treatment modalities. In conclusion, we demonstrate for the first time that
      exercise and beta-AR blockade can similarly ameliorate beta-AR signaling in the
      aged heart, leading to improved beta-AR responsiveness and corresponding LV
      inotropic reserve.

PMID- 17557920
TI  - Increased spontaneous tone in renal arteries of spontaneously hypertensive rats.
AB  - The spontaneous tone of vascular smooth muscle is augmented in hypertension. The
      present study examined the role of nitric oxide (NO), cyclooxygenase (COX),
      thromboxane A(2)/prostanoid (TP) and PGE(2)/prostanoid (EP-1) receptors, reactive
      oxygen species, and large-conductance Ca(2+)-activated K(+) (BK(Ca)) channels in
      the regulation of spontaneous tone in renal arteries of young and mature Wistar
      Kyoto (WKY) and spontaneously hypertensive rats (SHR). Rings of arteries, with
      and without endothelium, were suspended in a myograph for isometric force
      recording. Spontaneous tone (increase above initial tension) was observed only in
      arteries of mature SHR and was greater in arteries without endothelium. N(omega)
      nitro-L-arginine methyl ester (L-NAME, an inhibitor of NO synthases) induced
      larger contractions in arteries of SHR than WKY. Indomethacin (a COX inhibitor),
      SC-19220 (an EP-1 receptor antagonist), and terutroban (a TP receptor antagonist)
      reduced the L-NAME-evoked contractions. Tiron (a superoxide anion scavenger),
      catalase (an enzyme that degrades H(2)O(2)), and deferoxamine (a hydroxyl radical
      scavenger) augmented the L-NAME-induced contractions in arteries of mature SHR.
      Charybdotoxin (a BK(Ca) channel blocker) caused contractions in arteries of
      mature SHR without endothelium and in arteries with endothelium incubated with L
      NAME. A decreased protein level of endothelial NO synthase, an increased release
      of prostacyclin, and an increased expression of EP-1 receptors were observed in
      arteries of mature SHR. The present study suggests that spontaneous tone is
      precipitated by age and hypertension. The reduced production of NO, leading to
      decreased activation of BK(Ca) channels, may leave the actions of endogenous
      vasoconstrictors unopposed. COX products that activate EP-1 and TP receptors are
      involved in the development of spontaneous tone.

PMID- 17557921
TI  - Statins prevent cholinesterase inhibitor blockade of sympathetic alpha7-nAChR
      mediated currents in rat superior cervical ganglion neurons.
AB  - Statins are reported to be beneficial in treating a multitude of disorders
      including dementia due to Alzheimer disease (AD) and vascular dementia (VaD) with
      varying, yet-to-be determined mechanisms of actions. Although cholinesterase
      inhibitors (ChEIs) are still recommended as the primary drug of choice for AD and
      related diseases, their efficacy is frequently questioned. We recently reported
      that alpha7-neuronal acetylcholine nicotinic receptor (alpha7-nAChR)-mediated
      neurogenic vasodilation of porcine cerebral arteries was blocked by ChEIs, and
      this blockade was prevented by statin pretreatment. The exact mechanism of
      interaction between ChEIs and statins remains unclear. Activation of alpha7
      nAChRs located on perivascular postganglionic sympathetic nerve terminals
      releases norepinephrine, which then acts on presynaptic beta(2)-adrenoceptors
      located on neighboring nitrergic nerve terminals, resulting in nitric oxide
      release and vasodilation. The present study, therefore, was designed to determine
      whether interaction of ChEIs and statins occurs at the alpha7-nAChR level. We
      examined effects of concurrent application of ChEIs and statins on alpha7-nAChR
      mediated inward currents in primary neuronal cultures of rat superior cervical
      ganglion cells, the origin of the perivascular sympathetic innervation to the
      cerebral arteries. The results indicated that physostigmine, neostigmine, and
      galantamine inhibited choline- and nicotine-induced whole cell currents in a
      concentration-dependent manner. This inhibition, which was noncompetitive in
      nature, was prevented by concurrent application of mevastatin and lovastatin in a
      concentration-dependent manner. These results suggest that statins protect alpha7
      nAChR function directly at the receptor level. Since alpha7-nAChR is
      neuroprotective, having beneficial effects on memory and cerebral vascular
      function, its functional inhibition by ChEIs may explain in part the limitation
      of its effectiveness in AD and VaD therapy. Protection of alpha7-nAChR function
      from ChEI inhibition by concurrent administration of statins may provide an
      alternative strategy in improving the efficacy of AD and VaD therapy.

PMID- 17557922
TI  - Permeability of homotypic and heterotypic gap junction channels formed of cardiac
      connexins mCx30.2, Cx40, Cx43, and Cx45.
AB  - We examined the permeabilities of homotypic and heterotypic gap junction (GJ)
      channels formed of rodent connexins (Cx) 30.2, 40, 43, and 45, which are
      expressed in the heart and other tissues, using fluorescent dyes differing in net
      charge and molecular mass. Combining fluorescent imaging and electrophysiological
      recordings in the same cell pairs, we evaluated the single-channel permeability
      (P(gamma)). All homotypic channels were permeable to the anionic monovalent dye
      Alexa Fluor-350 (AF(350)), but mCx30.2 channels exhibited a significantly lower
      P(gamma) than the others. The anionic divalent dye Lucifer yellow (LY) remained
      permeant in Cx40, Cx43, and Cx45 channels, but transfer through mCx30.2 channels
      was not detected. Heterotypic channels generally exhibited P(gamma) values that
      were intermediate to the corresponding homotypic channels. P(gamma) values of
      mCx30.2/Cx40, mCx30.2/Cx43, or mCx30.2/Cx45 heterotypic channels for AF(350) were
      similar and approximately twofold higher than P(gamma) values of mCx30.2
      homotypic channels. Permeabilities for cationic dyes were assessed only
      qualitatively because of their binding to nucleic acids. All homotypic and
      heterotypic channel configurations were permeable to ethidium bromide and 4,6
      diamidino-2-phenylindole. Permeability for propidium iodide was limited only for
      GJ channels that contain at least one mCx30.2 hemichannel. In summary, we have
      demonstrated that Cx40, Cx43, and Cx45 are permeant to all examined cationic and
      anionic dyes, whereas mCx30.2 demonstrates permeation restrictions for molecules
      with molecular mass over approximately 400 Da. The ratio of single-channel
      conductance to permeability for AF(350) was approximately 40- to 170-fold higher
      for mCx30.2 than for Cx40, Cx43, and Cx45, suggesting that mCx30.2 GJs are
      notably more adapted to perform electrical rather than metabolic cell-cell
      communication.

PMID- 17557923
TI  - Oxygen distribution and consumption in the macaque retina.
AB  - The oxygen distribution in the retina of six anesthetized macaques was
      investigated as a model for retinal oxygenation in the human retina in and
      adjacent to the fovea. P(O2) was measured as a function of retinal depth under
      normal physiological conditions in light and dark adaptation with O(2)
      microelectrodes. Oxygen consumption (Q(O2)) of the photoreceptors was extracted
      by fitting a steady-state diffusion model to P(O2) measurements. In the
      perifovea, the P(O2) was 48 +/- 13 mmHg (mean and SD) at the choroid and fell to
      a minimum of 3.8 +/- 1.9 mmHg around the photoreceptor inner segments in dark
      adaptation, rising again toward the inner retina. The P(O2) in the inner half of
      the retina in darkness was 17.9 +/- 7.8 mmHg. When averaged over the outer
      retina, photoreceptor Q(O2) (called Q(av)) was 4.6 +/- 2.3 ml O(2).100 g(-1).min(
      1) under dark-adapted conditions. Illumination sufficient to saturate the rods
      reduced Q(av) to 72 +/- 11% of the dark-adapted value. Both perifoveal and foveal
      photoreceptors received most of their O(2) from the choroidal circulation. While
      foveal photoreceptors have more mitochondria, the Q(O2) of photoreceptors in the
      fovea was 68% of that in the perifovea. Oxygenation in macaque retina was similar
      to that previously found in cats and other mammals, reinforcing the relevance of
      nonprimate animal models for the study of retinal oxygenation, but there was a
      smaller reduction in Q(O2) with light than observed in cats, which may have
      implications for understanding the influence of light under some clinical
      conditions.

PMID- 17557924
TI  - Developmental changes in gene expression of Epac and its upregulation in
      myocardial hypertrophy.
AB  - Although it has been shown that Epac1 mRNA is expressed ubiquitously and Epac2
      mRNA predominantly in the brain and endocrine tissues, developmental and
      pathophysiological changes of these molecules have not been characterized.
      Developmental changes were analyzed in murine heart, brain, kidneys, and lungs by
      RT-PCR analysis, which revealed more drastic developmental changes of Epac2 mRNA
      than Epac1. Only the Epac2 mRNA in kidney showed a transient expression pattern
      with dramatic decline into adulthood. In addition to developmental changes, we
      found that Epac gene expression was upregulated in myocardial hypertrophy induced
      by chronic isoproterenol infusion or pressure overload by transverse aortic
      banding. Both Epac1 and Epac2 mRNA were upregulated in isoproterenol-induced left
      ventricular hypertrophy, whereas only Epac1 was increased in pressure overload
      induced hypertrophy. Stimulation of H9c2, cardiac myoblast cells, with fetal calf
      serum, which can induce myocyte hypertrophy, upregulated Epac1 protein
      expression. We also demonstrated that Epac was the limiting moiety, relative to
      Rap, in the Epac-Rap signaling pathway in terms of stoichiometry and that Epac
      stimulation led to the activation of ERK1/2. Our data suggest the functional
      involvement of Epac in organogenesis and also in physiological as well as
      pathophysiological processes, such as cardiac hypertrophy. Furthermore, our
      results suggest the importance of the stoichiometry of Epac over that of Rap in
      cellular biological effects.

PMID- 17557925
TI  - Hemichannels in cardiomyocytes open transiently during ischemia and contribute to
      reperfusion injury following brief ischemia.
AB  - The aim of this study was to investigate changes in hemichannel activity during
      in vitro simulated ischemia [oxygen-glucose deprivation (OGD)] and the
      contribution of hemichannels to ischemia-reperfusion injury in rat neonatal
      cardiomyocytes. Dye uptake assays showed that hemichannels opened as OGD
      progressed, peaking after 1 h, and then closed, returning to the pre-OGD state
      after 2 h of OGD. The increase in dye uptake after 1 h of OGD was inhibited by
      hemichannel blockers (lanthanum chloride and a connexin 43 mimetic peptide,
      Gap26). During OGD, intracellular Ca(2+) concentration ([Ca(2+)](i)) began to
      increase after 1 h and reached several micromolar after 2 h. After 1 h of OGD,
      Gap26 inhibited the increases in hemichannel activity and [Ca(2+)](i). In
      contrast, dantrolene [an endo(sarco)plasmic reticulum Ca(2+) release inhibitor]
      suppressed the increase in [Ca(2+)](i), but not in hemichannel activity. After 2
      h of OGD, the combined administration of 2',4'-dichlorobenzamil and dantrolene
      reduced [Ca(2+)](i) to <1 microM and increased hemichannel activity to the level
      attained after 1 h of OGD. Simulated ischemia-reperfusion, induced by 1 h of OGD
      followed by 2 h of recovery, reduced cell viability to 54% of the control level.
      The addition of Gap26 to OGD medium improved viability to 80% of the control
      level. In conclusion, this study demonstrated that 1) hemichannels open
      transiently during OGD, 2) closure of hemichannels, but not their opening, is
      regulated by an increase in [Ca(2+)](i) during OGD, and 3) open hemichannels
      contribute to cell injury during recovery from OGD.

PMID- 17557926
TI  - Genetic screening for pheochromocytoma: should SDHC gene analysis be included?
AB  - PGL3 syndrome is caused by mutations in the SDHC gene. At present, only a few
      families affected by SDHC mutations have been reported in the literature and in
      each of them the clinical presentation was characterised by paragangliomas
      located only in the head and neck regions. No evidence of thoracic or abdominal
      catecholamine-secreting chromaffin tumours has been reported to date. We report
      the case of a 15-year-old girl with hypertension and a norepinephrine-secreting
      abdominal paraganglioma who was found to harbour a novel nonsense SDHC mutation,
      demonstrating that the clinical presentation of PGL3 syndrome can be more diverse
      than expected.

PMID- 17557927
TI  - Congenital ichthyosis: mutations in ichthyin are associated with specific
      structural abnormalities in the granular layer of epidermis.
AB  - BACKGROUND: Autosomal recessive congenital ichthyosis (ARCI) is a heterogeneous
      group of skin disorders. Several mutant genes have been identified in ARCI, but
      the association between genotype and phenotype is poorly understood. METHODS: To
      investigate genotype-phenotype correlations in ARCI, we selected 27 patients from
      18 families with specific ultrastructural features of the epidermis. The
      characteristic findings using electron microscopy (EM) were abnormal lamellar
      bodies and elongated membranes in the stratum granulosum, classified as ARCI EM
      type III. DNA samples from a subset of affected individuals were screened for
      homozygous genomic regions, and a candidate gene region was identified on
      chromosome 5q33. The region coincides with the ichthyin gene, previously reported
      as mutated in ARCI. RESULTS: Mutation screening of ichthyin revealed missense or
      splice-site mutations in affected members from 16 of 18 (89%) families with
      characteristics of ARCI EM type III. In a control group of 18 patients with ARCI
      without EM findings consistent with type III, we identified one patient
      homozygous for a missense mutation in ichthyin. DISCUSSION: Our findings indicate
      a strong association between ultrastructural abnormalities in the granular layer
      of epidermis and ichthyin mutations. The results also suggest that EM provides a
      tool for specific diagnosis in a genetically homogenous subgroup of patients with
      ARCI.

PMID- 17557928
TI  - The IRF5 polymorphism in type 1 diabetes.
AB  - The interferon regulatory factor 5 gene (IRF5) has been shown to play a crucial
      role in harmful immune responses by induction of proinflammatory cytokines.
      Functional genetic variants associated with increased IRF5 expression of specific
      isoforms are associated with systemic lupus erythematosus (SLE) and it is
      possible that they may also predispose to other autoimmune disorders. We tested
      the association of two IRF5 SNPs, correlated with IRF5 expression and SLE risk,
      in 947 nuclear family trios type 1 diabetes (T1D) using the transmission
      disequilibrium test. Our results suggest that the functional IRF5 variations do
      not confer an obvious risk for T1D.

PMID- 17557929
TI  - Genetic association analysis of inositol polyphosphate phosphatase-like 1
      (INPPL1, SHIP2) variants with essential hypertension.
AB  - BACKGROUND: Inositol polyphosphate phosphatase-like 1 (INPPL1, SHIP2) is a
      negative regulator of insulin signalling and has previously been found to be
      associated with hypertension, obesity and type 2 diabetes in a cohort of families
      with diabetes in the UK presenting features of metabolic syndrome. In particular,
      a haplotype of three genetic polymorphisms (rs2276047, rs9886 and an
      insertion/deletion polymorphism in intron 1) was found to be strongly associated
      with increased susceptibility to hypertension. OBJECTIVE AND METHODS: To assess
      if INPPL1 variants play a direct role in the development of essential
      hypertension, we genotyped the three previously associated INPPL1 polymorphisms
      in a cohort of 712 families with severe hypertension from the BRIGHT study
      transmission disequilibrium test cohort. RESULTS: We found no evidence of
      significant association between hypertension and any of the three INPPL1
      polymorphisms or haplotypes (p>0.1). CONCLUSION: These results suggest that
      INPPL1 variants may be involved in mechanisms causing hypertension in metabolic
      syndrome patients specifically.

PMID- 17557930
TI  - P-selectin- and heparanase-dependent antimetastatic activity of non-anticoagulant
      heparins.
AB  - Vascular cell adhesion molecules, P- and L-selectins, facilitate metastasis of
      cancer cells in mice by mediating interactions with platelets, endothelium, and
      leukocytes. Heparanase is an endoglycosidase that degrades heparan sulfate of
      extracellular matrix, thereby promoting tumor invasion and metastasis. Heparin is
      known to efficiently attenuate metastasis in different tumor models. Here we
      identified modified, nonanticoagulant species of heparin that specifically
      inhibit selectin-mediated cell-cell interactions, heparanase enzymatic activity,
      or both. We show that selective inhibition of selectin interactions or heparanase
      with specific heparin derivatives in mouse models of MC-38 colon carcinoma and
      B16-BL6 melanoma attenuates metastasis. Selectin-specific heparin derivatives
      attenuated metastasis of MC-38 carcinoma, but heparanase-specific derivatives had
      no effect, in accordance with the virtual absence of heparanase activity in these
      cells. Heparin derivatives had no further effect on metastasis in mice deficient
      in P- and L-selectin, indicating that selectins are the primary targets of
      heparin antimetastatic activity. Selectin-specific and heparanase-specific
      derivatives attenuated metastasis of B16-BL6 melanomas to a similar extent. When
      mice were injected with a derivative containing both heparanase and selectin
      inhibitory activity, no additional attenuation of metastasis could be observed.
      Thus, selectin-specific heparin derivatives efficiently attenuated metastasis of
      both tumor cell types whereas inhibition of heparanase led to reduction of
      metastasis only in tumor cells producing heparanase.

PMID- 17557931
TI  - Laminar shear stress acts as a switch to regulate divergent functions of NF
      kappaB in endothelial cells.
AB  - Regions of the arterial tree exposed to laminar flow, which exerts high shear
      stress, are protected from inflammation, endothelial cell (EC) death and
      atherosclerosis. TNFalpha activates NF-kappaB transcription factors, which
      potentially exert dual functions by inducing both proinflammatory and
      cytoprotective transcripts. We assessed whether laminar shear stress protects EC
      by modulating NF-kappaB function. Human umbilical vein EC (HUVEC) were cultured
      under shear stress (12 dynes/cm2 for 16 h) using a parallel-plate flow chamber or
      were maintained in static conditions. Comparative real-time PCR revealed that
      preshearing significantly alters transcriptional responses to TNFalpha by
      enhancing the expression of cytoprotective molecules (Bcl-2, MnSOD, GADD45beta,
      A1) and suppressing proinflammatory transcripts (E-selectin, VCAM-1, IL-8). We
      demonstrated using assays of nuclear localization, NF-kappaB subunit
      phosphorylation, DNA-binding, and transcriptional activity that NF-kappaB is
      activated by TNFalpha in presheared HUVEC. Furthermore, a specific inhibitor
      revealed that NF-kappaB is essential for the induction of cytoprotective
      transcripts in presheared EC. Finally, we observed that NF-kappaB can be
      activated in vascular endothelium exposed to laminar shear stress in NF-kappaB
      luciferase reporter mice, thus validating our cell culture experiments. We
      conclude that shear stress primes EC for enhanced NF-kappaB-dependent
      cytoprotective responsiveness while attenuating proinflammatory activation. Thus
      modulation of NF-kappaB function may underlie the atheroprotective effects of
      laminar shear stress.

PMID- 17557932
TI  - Mexican immigrant mothers' expectations for children's health services.
AB  - Women of Mexican descent living in the United States raise children who use
      health care services. What do immigrant Mexican mothers expect from children's
      health care services? And how do their expectations for children's health
      services compare to acculturated Mexican American mothers' expectations? This
      focused ethnographic study, based on repeated interviews with 28 mothers of
      varying acculturation levels, describes their expectations and experiences with
      children's health care services in the United States. Findings support a shared
      core of expectations for both Mexican immigrant and Mexican American mothers, and
      differences in health care access and financing, time spent in health care
      encounters, and cultural and linguistic expectations for care. Health care
      providers can use this information to approach Mexican-descent mothers and
      children with their expectations in mind, and craft a negotiated plan of care
      congruent with their expectations.

PMID- 17557933
TI  - Effects of support on the initiation and duration of breastfeeding.
AB  - Researchers attempted to increase the initiation of breastfeeding and its
      duration to 6 months among a group of low-income, Hispanic women through an
      intervention program which included prenatal education and home based postpartum
      support. All participants were telephoned after delivery to determine infant
      feeding method. Duration of breastfeeding was determined by counting the number
      of days from initiation to the last day the baby was put to the breast. The
      Bayesian approach was used for the statistical analyses. In the intervention
      group, the propensity to initiate breastfeeding exceeded that of the control
      group. Results indicate the intervention group had twice (2.31) the odds of
      starting breastfeeding, twice (1.84-3.15) the odds of continuing to breastfeed
      for 6 months, and only half (.50-.54) the tendency to quit at any one time than
      did the control group.

PMID- 17557934
TI  - Clinical constructions by nurses in Korea, Norway, and the United States.
AB  - Nursing practice involves engagement of nurses in clinical fields through
      deliberation and enactment. In the phase of deliberation, nurses observe,
      recognize, form ideas about and decide on clinical situations, and construct
      clinical pictures. Clinical pictures are critically connected to nursing
      enactments, thus it is important to discover how nurses arrive at clinical
      pictures. The purpose of this article is to describe how nurses construct
      meanings of clinical situations and arrive at specific clinical pictures. The
      results are from a clinical fieldwork study replicated in Korea, Norway, and the
      United States, with samples of nurses working in acute-care hospitals. Data were
      collected through participant observations and in-depth interviews. A general
      model of clinical construction was derived from the results, which specifies four
      dimensions (i.e., problem, progress, status, and particularism) as the bases for
      clinical picture evocations. Clinical pictures are constituted by nurses'
      elicitations of meanings of clinical situations on these dimensions.

PMID- 17557936
TI  - Transgenic RNA interference in mice.
AB  - The discovery that small interfering RNA duplexes (siRNA) can silence gene
      expression in mammalian cells has revolutionized biomedical research. The most
      successful application of the discovery has been to study gene function in
      cultured human or mouse cells. However, the knockdown effect of siRNA is only
      transient. To achieve a more sustained gene-silencing effect, shRNA (small
      hairpin RNA) expressed from a vector is preferred. An additional benefit of shRNA
      is that RNA interference (RNAi) can now be applied in vivo through delivering
      shRNA-expressing vectors by transgenic technology. Transgenic RNAi not only
      allows the study of biological processes not present in cultured cells but also
      offers chronic therapeutic potentials. In this review, we will summarize the
      developments in the generation of transgenic RNAi mice.

PMID- 17557937
TI  - Resurgence of cardiac t-tubule research.
AB  - The transverse tubules of mammalian cardiac ventricular myocytes are
      invaginations of the surface membrane. Recent data have revealed that their
      structure and function are more complex than previously believed. Here, we review
      current knowledge about their role in cardiac function, focusing on Ca2+
      signaling and changes observed in pathological conditions.

PMID- 17557938
TI  - G-protein coupled receptor signaling in myocardium: not for the faint of heart.
AB  - Catecholamines, endothelin-1 and angiotensin II are among a diverse group of
      diffusible extracellular signals that regulate pump function of the heart by
      binding to G-protein coupled receptors (GPCR). When the body demands a temporary
      boost of power output or if temporary budgeting of resources is required, these
      signals can adjust heart rate and contractile strength to maintain continuous
      perfusion of all vascular beds with nutrient- and oxygen-rich blood. Given
      adequate time in the face of prolonged challenges, activation of GPCRs can also
      promote "remodeling of the heart" by increasing cell size, organ size, and
      chamber dimensions, or by varying tissue composition and altering the expression
      of protein isoforms controlling excitability and contractility. A common feature
      of heart disease is the state of chronic activation of GPCR signaling systems.
      Paradoxically, whereas acute activation is beneficial, chronic activation often
      contributes to further deterioration of cardiac performance. A better
      understanding of how chronic GPCR activation contributes to the development of
      heart disease is needed so that it can be translated into better prevention and
      therapeutic strategies in the clinic.

PMID- 17557939
TI  - K+ -dependent Na+/Ca2+ exchangers: key contributors to Ca2+ signaling.
AB  - An elevation in cytosolic Ca2+ is a universal signaling mechanism that controls a
      vast array of physiological processes. K+ -dependent Na+/Ca2+ exchangers are a
      newly identified family of Ca2+ efflux transporters that play important and
      diverse roles in cellular Ca2+ homeostasis.

PMID- 17557940
TI  - Endoplasmic reticulum stress: signaling the unfolded protein response.
AB  - The endoplasmic reticulum (ER) is the cellular site of newly synthesized
      secretory and membrane proteins. Such proteins must be properly folded and
      posttranslationally modified before exit from the organelle. Proper protein
      folding and modification requires molecular chaperone proteins as well as an ER
      environment conducive for these reactions. When ER lumenal conditions are altered
      or chaperone capacity is overwhelmed, the cell activates signaling cascades that
      attempt to deal with the altered conditions and restore a favorable folding
      environment. Such alterations are referred to as ER stress, and the response
      activated is the unfolded protein response (UPR). When the UPR is perturbed or
      not sufficient to deal with the stress conditions, apoptotic cell death is
      initiated. This review will examine UPR signaling that results in cell protective
      responses, as well as the mechanisms leading to apoptosis induction, which can
      lead to pathological states due to chronic ER stress.

PMID- 17557941
TI  - Inherited renal acidoses.
AB  - Inherited acidosis may result from a primary renal defect in acid-base handling,
      emphasizing the central role of the kidney in control of body pH; as a secondary
      phenomenon resulting from abnormal renal electrolyte handling; or from excess
      production of acid elsewhere in the body. Here, we review our current
      understanding of the inherited renal acidoses at a genetic and molecular level.

PMID- 17557942
TI  - Cystic fibrosis: lessons from the sweat gland.
AB  - Lessons from the sweat gland on cystic fibrosis (CF) began long before modern
      medicine became a science. In European folklore, the curse that "a child that
      taste salty when kissed will soon die" (Alonso y de los Ruyzes de Fonteca J. Diez
      Previlegios para Mugeres Prenadas. Henares, Spain, 1606) has been taken by many
      as a direct reference to cystic fibrosis [Busch R. Acta Univ Carol Med (Praha)
      36: 13-15, 1990]. The high salt concentration in sweat from patients with CF is
      now accepted as almost pathognomonic with this fatal genetic disease, but the
      earliest descriptions of cystic fibrosis as a disease entity did not mention
      sweat or sweat glands (Andersen DH. Am J Dis Child 56: 344-399, 1938; Andersen
      DH, Hodges RG. Am J Dis Child 72: 62-80, 1946). Nonetheless, defective sweating
      soon became an inseparable, and major, component of the constellation of symptoms
      that diagnose "cystic fibrosis" (Davis PB. Am J Respir Crit Care Med 173: 475
      482, 2006). The sweat gland has played a foremost role in diagnosing, defining
      pathophysiology, debunking misconceptions, and increasing our understanding of
      the effects of the disease on organs, tissues, cells, and molecules. The sweat
      gland has taught us much.

PMID- 17557943
TI  - Is the whole larger than the sum of the parts? The promise of combining physical
      activity and diet to improve cancer outcomes.

PMID- 17557944
TI  - A step in the maturation of the field of lifestyle change interventions.

PMID- 17557945
TI  - Multitarget tyrosine kinase inhibition: [and the winner is...].

PMID- 17557946
TI  - Depression and risk of cancer progression: an elusive link.

PMID- 17557947
TI  - Greater survival after breast cancer in physically active women with high
      vegetable-fruit intake regardless of obesity.
AB  - PURPOSE: Single-variable analyses have associated physical activity, diet, and
      obesity with survival after breast cancer. This report investigates interactions
      among these variables. PATIENTS AND METHODS: A prospective study was performed of
      1,490 women diagnosed and treated for early-stage breast cancer between 1991 and
      2000. Enrollment was an average of 2 years postdiagnosis. Only seven women were
      lost to follow-up through December 2005. RESULTS: In univariate analysis, reduced
      mortality was weakly associated with higher vegetable-fruit consumption,
      increased physical activity, and a body mass index that was neither low weight
      nor obese. In a multivariate Cox model, only the combination of consuming five or
      more daily servings of vegetables-fruits, and accumulating 540+ metabolic
      equivalent tasks-min/wk (equivalent to walking 30 minutes 6 d/wk), was associated
      with a significant survival advantage (hazard ratio, 0.56; 95% CI, 0.31 to 0.98).
      The approximate 50% reduction in risk associated with these healthy lifestyle
      behaviors was observed in both obese and nonobese women, although fewer obese
      women were physically active with a healthy dietary pattern (16% v 30%). Among
      those who adhered to this healthy lifestyle, there was no apparent effect of
      obesity on survival. The effect was stronger in women who had hormone receptor
      positive cancers. CONCLUSION: A minority of breast cancer survivors follow a
      healthy lifestyle that includes both recommended intakes of vegetables-fruits and
      moderate levels of physical activity. The strong protective effect observed
      suggests a need for additional investigation of the effect of the combined
      influence of diet and physical activity on breast cancer survival.

PMID- 17557948
TI  - Randomized controlled trial of the effects of print materials and step pedometers
      on physical activity and quality of life in breast cancer survivors.
AB  - PURPOSE: To determine the effects of breast cancer-specific print materials and
      step pedometers on physical activity (PA) and quality of life (QoL) in breast
      cancer survivors. PATIENTS AND METHODS: Breast cancer survivors (N = 377) were
      randomly assigned to receive one of the following: a standard public health
      recommendation for PA, previously developed breast cancer-specific PA print
      materials, a step pedometer, or a combination of breast cancer-specific print
      materials and step pedometers. The primary outcome was self-reported
      moderate/vigorous PA minutes per week. Secondary outcomes were QoL (Functional
      Assessment of Cancer Therapy-Breast), fatigue, self-reported brisk walking, and
      objective step counts. Assessments were conducted at baseline and
      postintervention (12 weeks). RESULTS: Attrition was 10.3% (39 of 377). On the
      basis of linear mixed-model analyses, PA increased by 30 minutes/week in the
      standard recommendation group compared with 70 minutes/week in the print material
      group (mean difference, 39 minutes/week; 95% CI = -10 to 89; d = 0.25; P = .117),
      89 minutes/week in the pedometer group (mean difference, 59 minutes/week; 95% CI,
      11 to 108; d = 0.38; P = .017), and 87 minutes/week in the combined group (mean
      difference, 57 minutes/week; 95% CI, 8 to 106; d = 0.37; P = .022). For brisk
      walking minutes/week, all three intervention groups reported significantly
      greater increases than the standard recommendation group. The combined group also
      reported significantly improved QoL (mean difference, 5.8; 95% CI, 2.0 to 9.6; d
      = 0.33; P = .003) and reduced fatigue (mean difference, 2.3; 95% CI, 0.0 to 4.7;
      d = 0.25; P = .052) compared with the standard recommendation group. CONCLUSION:
      Breast cancer-specific PA print materials and pedometers may be effective
      strategies for increasing PA and QoL in breast cancer survivors. A combined
      approach appears to be optimal. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov
      Identifier NCT00221221

PMID- 17557949
TI  - Safety, pharmacokinetics, and efficacy of AMG 706, an oral multikinase inhibitor,
      in patients with advanced solid tumors.
AB  - PURPOSE: AMG 706 is an investigational, orally bioavailable inhibitor of vascular
      endothelial growth factor receptors 1, 2, and 3, platelet-derived growth factor
      receptor, and stem-cell factor receptor. This phase I, dose-finding study
      evaluated the safety, pharmacokinetics, and pharmacodynamics of AMG 706 in
      patients with refractory advanced solid tumors. PATIENTS AND METHODS: AMG 706 was
      administered at escalating doses of 50 to 175 mg once daily or 25 mg bid for the
      first 21 days of a 28-day cycle. The 125-mg once-daily dose was also administered
      continuously. The maximum-tolerated dose (MTD), safety, pharmacokinetics, tumor
      response, and serum levels of proangiogenic markers were determined. RESULTS:
      Seventy-one patients received AMG 706. The MTD was 125 mg once daily administered
      continuously. The most frequent adverse events were fatigue (55%), diarrhea
      (51%), nausea (44%), and hypertension (42%). Plasma AMG 706 concentrations
      increased in a dose-proportional manner with no accumulation after multiple
      doses. Five patients (7%) had a partial response, 35 patients (49%) had stable
      disease (at least through day 50), and 31 patients (44%) had progressive disease.
      Changes in tumor size correlated significantly with an increase in placental
      growth factor (P = .003) and a decrease in soluble kinase domain receptor (P =
      .001). CONCLUSION: In this study of patients with advanced refractory solid
      tumors, AMG 706 was well tolerated and displayed favorable pharmacokinetics and
      evidence of antitumor activity. Additional studies of AMG 706 as monotherapy and
      in combination with various agents are ongoing.

PMID- 17557950
TI  - Phase II study: integrated palliative care in newly diagnosed advanced non-small
      cell lung cancer patients.
AB  - PURPOSE: To assess the feasibility of early palliative care in the ambulatory
      setting in patients with newly diagnosed advanced non-small-cell lung cancer
      (NSCLC). PATIENTS AND METHODS: Patients were eligible if they had a performance
      status of 0 to 1 and were within 8 weeks of diagnosis of advanced NSCLC.
      Participants received integrated care from oncology and palliative care
      throughout the course of their disease. Participants were scheduled to meet with
      the palliative care team (PCT) and complete quality-of-life (QOL) and mood
      questionnaires monthly for 6 months. The study was deemed feasible if 64% of
      patients completed at least 50% of their scheduled visits and QOL assessments.
      RESULTS: Fifty-one patients were enrolled onto the trial. One died within 72
      hours and was not assessable. Ninety percent (95% CI, 0.78 to 0.96) of study
      participants complied with at least 50% of the palliative care visits. Eight-six
      percent (95% CI, 0.73 to 0.94) of the participants met the full feasibility
      requirements by both meeting with the PCT and completing QOL assessments at least
      50% of the time. QOL and mood analyses confirmed the high symptom burden in
      patients with newly diagnosed advanced NSCLC. At least 50% of participants
      experienced some degree of shortness of breath, cough, difficulty breathing,
      appetite loss, weight loss, or unclear thinking at their baseline assessment.
      More than one third of patients had a probable mood disorder at baseline.
      CONCLUSION: Integrated palliative and oncology care is feasible in ambulatory
      patients with advanced NSCLC.

PMID- 17557951
TI  - Impact of adoption of chemoradiotherapy on the outcome of cervical cancer in
      Ontario: results of a population-based cohort study.
AB  - PURPOSE: To describe the adoption of concurrent cisplatin-based chemoradiotherapy
      (C-CRT), and to evaluate its impact on the outcome of cervical cancer in Ontario.
      METHODS: We used a population-based cancer registry to identify the 4,069
      patients with invasive carcinoma of the cervix diagnosed in Ontario between 1992
      and 2001. We linked electronic records of treatment to the registry. We described
      time trends in the use of C-CRT, and we compared survival before and after
      widespread adoption of C-CRT. RESULTS: Over the study period, the proportion of
      patients treated with primary radical radiotherapy (RT) remained constant at
      approximately 42%. Between 1992 and 1998, less than 10% of RT cases received
      chemotherapy. Early in 1999, there was rapid adoption of C-CRT. Between 1999 and
      2001, more than 60% of RT cases received C-CRT. There was a contemporaneous
      increase in overall 3-year survival from 71.1% in the 1995 to 1998 cohort to
      75.9% in the 1999 to 2001 cohort (P = .03). There was no change in survival in
      patients treated with surgery alone. However, there was a significant increase in
      3-year survival from 58.6% in the 1995 to 1998 cohort to 69.8% in the 1999 to
      2001 cohort (P < .01) in the subpopulation of patients treated with primary RT +/
      chemotherapy. CONCLUSION: The adoption of C-CRT was associated with a
      significant improvement in overall survival of cervical cancer at the population
      level. The magnitude of the benefit of C-CRT in the general population was
      consistent with the results of the relevant clinical trials.

PMID- 17557952
TI  - Referral patterns, treatment choices, and outcomes in locoregional esophageal
      cancer: a population-based analysis of elderly patients.
AB  - PURPOSE To determine the impact of demographics and comorbidity on access to
      specialists' services, treatment, and outcome for patients with locoregional
      esophageal cancer. PATIENTS AND METHODS We performed a retrospective cohort study
      of 3,538 patients older than age 65 years who were diagnosed with locoregional
      esophageal cancer between 1991 and 1999 in one of 11 regions monitored by the
      Surveillance, Epidemiology, and End Results tumor program. We examined linked
      Medicare claims for assessment by a surgeon, radiation oncologist, or medical
      oncologist and subsequent treatment with surgery, radiation, or chemotherapy.
      Logistic regression analyses were performed for seeing a specialist and for
      undergoing treatment according to age, sex, race, socioeconomic status,
      geographic region, and presence of comorbidities. Cox proportional hazards
      analyses were performed to estimate hazard ratios (HRs) for survival with and
      without adjustment for treatment received. Results Seeing a cancer specialist
      depended especially on age and region of diagnosis. These same factors were also
      related to subsequent treatment decisions, but associations were reversed in some
      regions, such that treatment depended less on region. Older patients had poorer
      survival (HR = 2.0 for 85+ v 65 to 69 years), which was partly explained by
      treatment received (HR decreased to 1.5 when adjusted for treatment). CONCLUSION
      Older patients have less intensive treatment of esophageal cancer, which is
      explained by both a lower rate of seeing a cancer specialist and by less
      intensive treatment once seen. Referring physicians and treating specialists must
      ensure that elderly patients are not deprived of the opportunity to consider all
      of their treatment options.

PMID- 17557953
TI  - Depression, immunity, and survival in patients with hepatobiliary carcinoma.
AB  - PURPOSE: The aims of the present study were to assess the prevalence of
      depressive symptoms at diagnosis, test the association between depressive
      symptoms and survival, and preliminarily test a mediational model of depression,
      immunity, and survival in patients with hepatobiliary carcinoma (HBC). PATIENTS
      AND METHODS: One hundred one patients diagnosed with HBC were prospectively
      studied. Depressive symptoms were measured at diagnosis using the Center for
      Epidemiological Studies Depression Scale (CES-D). Sociodemographic and disease
      specific data were gathered from the patients' charts. In a subsample of
      patients, stress; alcohol, tobacco, and drug use; sleep quality; physical
      activity; social support; natural killer (NK) cell number and cytotoxicity; and
      plasma levels of interleukin (IL) -4, IL-5, tumor necrosis factor alpha, and
      interferon gamma were measured. Survival was measured from date of diagnosis to
      death. RESULTS: At diagnosis, 37% of patients reported a CES-D score of > or = 16
      (clinical range). Using Cox regression analysis, sociodemographic and disease
      specific variables and CES-D score significantly predicted survival (Breslow chi2
      = 32.4, P = .006). Only vascular invasion (P = .001) and CES-D score > or = 16 (P
      = .03) were significant predictors. In a subsample of 23 patients, patients who
      reported a CES-D score of > or = 16 were found to have significantly lower NK
      cell numbers than patients who reported a CES-D score of less than 16 (F1,21 =
      9.39, P = .003). A robust trend was found in which NK cell number was associated
      with survival. A mediational model linking depressive symptoms and survival, with
      NK cell number as a mediator, was preliminarily supported. CONCLUSION: Secondary
      to the high prevalence of depressive symptoms and impact on survival,
      psychological and pharmacologic interventions should be designed and implemented
      in patients diagnosed with HBC.

PMID- 17557954
TI  - Phase II study of erlotinib in patients with malignant pleural mesothelioma: a
      Southwest Oncology Group Study.
AB  - PURPOSE: Malignant pleural mesothelioma (MPM) expresses high levels of epidermal
      growth factor receptor (EGFR), and preclinical studies have identified antitumor
      activity of EGFR tyrosine kinase inhibitors (TKIs) in MPM. We conducted a phase
      II trial of the EGFR TKI erlotinib in previously untreated patients with MPM.
      PATIENTS AND METHODS: Patients with measurable and nonmeasurable disease were
      treated with erlotinib 150 mg/d on days 1 through 28 of each 28-day dosing cycle.
      Archived patient tumors were analyzed for immunohistochemical expression of EGFR,
      phospho-EGFR, human epidermal growth factor receptor 2 (HER2), phospho
      extracellular signal-regulated kinase (ERK), and phosphatase and tensin homolog
      (PTEN) and phosphorylation of members of the phosphatidylinositol 3-kinase/Akt
      signaling pathway. RESULTS: Sixty-three patients were treated on the study. EGFR
      was highly expressed in 75% of patient tumors, as was phospho-ERK (82%), phospho
      Akt (84%), phospho-mammalian target of rapamycin (74%), and phospho-forkhead
      (74%). HER2 was rarely expressed, and loss of PTEN was rare. For 33 patients with
      measurable disease, there were no objective responses; 14 patients (42%) had
      stable disease, 15 patients (45%) had disease progression, and four patients had
      inadequate assessments to determine response. Toxicities were mainly
      constitutional (51%), dermatologic (82%), and GI (52%); there was one death on
      trial, which was related to dyspnea. Median overall survival time was 10 months;
      1-year survival rate was 43%; and median progression-free survival time was 2
      months. CONCLUSION: Single-agent erlotinib was not effective in MPM, despite high
      expression of EGFR. Activation of the ERK and phosphatidylinositol 3-kinase/Akt
      downstream pathways are possible resistance mechanisms to EGFR TKI. The activated
      phosphatidylinositol 3-kinase/Akt pathway is a potential therapeutic target for
      MPM.

PMID- 17557955
TI  - Understanding parents' approaches to care and treatment of children with cancer
      when standard therapy has failed.
AB  - PURPOSE: To examine US and United Kingdom (UK) parents' approaches to care and
      treatment when standard therapy has failed and consider implications for clinical
      practice. METHODS: We conducted a prospective, ethnographic study of parents,
      patients, and staff, including participant-observation; open-ended,
      semistructured interviews; and review of medical records at a US and UK pediatric
      oncology center. Thirty-four children (n = 17 US, 17 UK), whose disease had
      recurred with less than 30% chance of cure, were enrolled between March 2001 and
      June 2002 and followed until death (n = 11 US, 14 UK) or close of study in
      December 2005 (n = 6 US, 3 UK). RESULTS: There were no major differences between
      parents' approaches in the US and UK despite differences in health care systems,
      institutions, and parents' religion or ethnicity. All parents continued to have
      or request meetings with the oncologist and investigative procedures. No parent
      initiated discontinuation of cancer- or symptom-directed interventions. In 28 of
      34 cases (13 US, 15 UK), parents continued to pursue cancer-directed therapies;
      in 16 of 28 cases (seven US, nine UK), parents initiated inquires beyond what was
      offered. CONCLUSION: Understanding parents' behavior requires attention to the
      reason and emotion they bring to decision making and their children's care, their
      unique responsibilities as parents, and what they learn throughout the illness.
      Parents do not see cancer-directed therapy and symptom-directed care as mutually
      exclusive, alternative approaches. Parents will not be constrained by what the
      oncologist offers. Physicians and parents discuss and negotiate care and
      treatment throughout the illness. Our findings suggest developing integrative
      care models incorporating cancer-directed, symptom-directed, and supportive care
      throughout the illness; they are most consistent with parents' approaches and
      advances in pediatric oncology.

PMID- 17557956
TI  - Influence of androgen suppression therapy for prostate cancer on the frequency
      and timing of fatal myocardial infarctions.
AB  - PURPOSE: We evaluated whether the timing of fatal myocardial infarction (MI) was
      influenced by the administration of androgen suppression therapy (AST). PATIENTS
      AND METHODS: The study cohort comprised 1,372 men who were enrolled onto three
      randomized trials between February 1995 and June 2001. In the three trials, the
      men were randomly assigned to receive radiation therapy with 0 versus 3 versus 6,
      3 versus 8, or 0 versus 6 months of AST. Fine and Gray's regression was used to
      determine the clinical factors associated with the time to fatal MI, and
      estimates of time to fatal MI were calculated using a cumulative incidence
      method. When comparing the cumulative incidence estimates using Gray's k-sample P
      values, increased weight was ascribed to the earlier data because recovery of
      testosterone is expected for most men within 2 years after short-course AST.
      RESULTS: Men age 65 years or older who received 6 months of AST experienced
      shorter times to fatal MIs compared with men in this age group who did not
      receive AST (P = .017) and men younger than 65 years (P = .016). No significant
      difference (P = .97) was observed in the time to fatal MIs in men age 65 years or
      older who received 6 to 8 months of AST compared with 3 months of AST.
      CONCLUSION: The use of AST is associated with earlier onset of fatal MIs in men
      age 65 years or older who are treated for 6 months compared with men who are not
      treated with AST.

PMID- 17557957
TI  - Cost effectiveness of adjuvant interferon in node-positive melanoma.
AB  - PURPOSE: To assess the benefits of adjuvant high-dose interferon alfa (HDI)
      treatment for patients with high-risk melanoma. METHODS: We designed a decision
      analytic probabilistic Markov model to simulate the natural history of patients
      with stage IIIA, IIIB, and IIIC melanoma and evaluate the outcomes with and
      without HDI treatment. Outcomes were in quality-adjusted life years (QALYs) and
      incremental cost-effectiveness ratios (ICERs). Probability estimates and costs
      were derived from primary patient level data, while the efficacy of HDI and
      associated utilities were determined from published reports. The base-case
      analysis was a cohort of 50-year-old patients. RESULTS: HDI increased the median
      life expectancy in patients with stage III melanoma from 3.75 years in the
      observation cohort to 4.42 years in the HDI cohort. The difference in QALYs
      ranged from 0.31 years for stage IIIA patients to 0.60 years for stage IIIC
      patients treated with HDI. HDI was cost effective in patients with stage IIIB and
      IIIC melanoma, with ICERs of $95,304 and $76,068 per QALY gained, respectively.
      Using a threshold of $100,000 per QALY gained, HDI was cost effective for all
      stage III patients younger than 52 years. HDI was not cost effective for patients
      with stage IIIA disease and for subsets of patients older than 63 years with
      stage IIIB disease. CONCLUSION: Our model demonstrates that the probability of
      HDI being cost effective varies substantially by melanoma substage. HDI showed
      the greatest benefit in terms of QALYs and was most cost effective in patients
      younger than 60 years with stage IIIC disease.

PMID- 17557958
TI  - Risk for secondary thyroid carcinoma after hematopoietic stem-cell
      transplantation: an EBMT Late Effects Working Party Study.
AB  - PURPOSE: The effects of hematopoietic stem-cell transplantation (HSCT) on thyroid
      carcinogenesis needs to be determined in a large population. This study evaluates
      the incidence and the risk factors contributing to secondary thyroid carcinoma
      (STC) in patients who receive transplantation. PATIENTS AND METHODS: We performed
      a retrospective investigational study, comparing data obtained by means of a two
      step questionnaire from the 166 centers who replied, and data reported to the
      European Group for Blood and Marrow Transplantation (EBMT) registry on their
      transplantation activity. During the follow-up period (1985 to 2003), 32
      instances of STC were found within the EBMT cohort of 68,936 patients who
      received transplants. These patients were then compared with age- and sex
      specific incidence rates in the European population and risk factors for STC were
      analyzed. RESULTS: The standardized incidence ratios (SIRs) of STC in the
      population who underwent transplantation was 3.26, in comparison with the
      European population. Multivariate analysis revealed that young age at
      transplantation was the strongest risk factor for STC (relative risk [RR], 24.61
      for age 0 to 10 years; RR, 4.80 for age 11 to 20). Other risk factors were
      irradiation (RR, 3.44), female sex (RR, 2.79), and chronic graft-versus-host
      disease (RR, 2.94). Nine patients showed no clinical signs of thyroid illness at
      diagnosis. Total thyroidectomy and iodine ablation was the standard treatment for
      the majority of patients, and only one patient died due to STC progression.
      CONCLUSION: Long-term survivors of HSCT are at risk for STCs. These results
      should promote efforts in screening for early detection and treatment guidelines
      of secondary thyroid cancer after HSCT, especially in patients who receive
      transplants during childhood and adolescence.

PMID- 17557959
TI  - New waves of discovery: modeling cancer in zebrafish.

PMID- 17557960
TI  - Adult T-cell leukemia/lymphoma with a mixed CD4+ and CD8+ phenotype and indolent
      course.

PMID- 17557961
TI  - Persistent positron emission tomography-positive liver lesions after successful
      chemotherapy in mediastinal seminoma.

PMID- 17557962
TI  - Dexamethasone-induced posterior reversible encephalopathy syndrome.

PMID- 17557963
TI  - Bimodal population or pathologist artifact?

PMID- 17557964
TI  - Late cardiac morbidity and mortality in early-stage breast cancer patients after
      breast-conservation treatment.

PMID- 17557965
TI  - Docetaxel for advanced gastric cancer?

PMID- 17557966
TI  - Genetic changes of CEBPA in cancer: mutations or polymorphisms?

PMID- 17557967
TI  - Bronchoalveolar lavage for diagnosis of miliary lung metastases from papillary
      thyroid carcinoma.

PMID- 17557968
TI  - Targeting human epidermal growth factor receptor 2: it is time to kill kinase
      death human epidermal growth factor receptor 3.

PMID- 17557969
TI  - The identification of effective programs to prevent and treat overweight
      preschool children.

PMID- 17557970
TI  - So, is leptin good or bad in chronic kidney disease?

PMID- 17557972
TI  - Interventions to prevent or treat obesity in preschool children: a review of
      evaluated programs.
AB  - OBJECTIVE: To identify effective programs to prevent or treat overweight among 2-
      to <6-year-old children. RESEARCH METHODS AND PROCEDURES: We searched six
      databases to identify evaluated intervention programs assessing changes in weight
      status or body fat and systematically summarized study attributes and outcomes.
      RESULTS: Four of the seven studies (two intervention, two prevention) documented
      significant reductions in weight status or body fat. Among these, three sustained
      reductions at 1 or 2 years after program initiation, three incorporated a
      framework/theory, two actively and one passively involved parents, three included
      multicomponent strategies, and all four monitored behavioral changes. Of the
      three (prevention) studies that did not show reduction in weight or fat status,
      all performed assessments between 4 and 9 months after program initiation, and
      one used a multicomponent strategy. Other significant changes reported were
      reductions in television viewing, cholesterol, and parental restriction of child
      feeding. DISCUSSION: The paucity of studies limits our ability to generalize
      findings. Among the available studies, multicomponent programs with 1- to 2-year
      follow-up in clinics or child care settings were successful in their impact on
      weight; they were likely enhanced by parental involvement. Both treatment
      programs and two of five prevention programs reduced weight/fat status. Our
      review highlights the need to evaluate more programs, advocate for use of a
      framework/behavioral theory and objective behavioral measures, further examine
      the impact of involving parents and the impact of intervention duration and
      follow-up time, strengthen prevention programs, and further evaluate successful
      programs in other settings and among other racial/ethnic groups.

PMID- 17557973
TI  - Metabolic and behavioral compensatory responses to exercise interventions:
      barriers to weight loss.
AB  - An activity-induced increase in energy expenditure theoretically disturbs energy
      balance (EB) by creating an acute energy deficit. Compensatory responses could
      influence the weight loss associated with the energy deficit. Individual
      variability in compensation for perturbations in EB could partly explain why some
      individuals fail to lose weight with exercise. It is accepted that the regulatory
      system will readily defend impositions that promote a negative EB. Therefore, a
      criticism of exercise interventions is that they will be ineffective and futile
      methods of weight control because the acute energy deficit is counteracted.
      Compensation for exercise-induced energy deficits can be categorized into
      behavioral or metabolic responses and automatic or volitional. An automatic
      compensatory response is a biological inevitability and considered to be
      obligatory. An automatic compensatory response is typically a metabolic
      consequence (e.g., reduced resting metabolic rate) of a negative EB. In contrast,
      a volitional compensatory response tends to be deliberate and behavioral, which
      the individual intentionally performs (e.g., increased snack intake). The purpose
      of this review is to highlight the various metabolic and behavioral compensatory
      responses that could reduce the effectiveness of exercise and explain why some
      individuals experience a lower than expected weight loss. We propose that the
      extent and degree of compensation will vary between individuals. That is, some
      individuals will be predisposed to compensatory responses that render them
      resistant to the weight loss benefits theoretically associated with an exercise
      induced increase in energy expenditure. Therefore, given the inter-individual
      variability in behavioral and metabolic compensatory responses, exercise
      prescriptions might be more effective if tailored to suit individuals.

PMID- 17557971
TI  - Preventing excessive weight gain in adolescents: interpersonal psychotherapy for
      binge eating.
AB  - The most prevalent disordered eating pattern described in overweight youth is
      loss of control (LOC) eating, during which individuals experience an inability to
      control the type or amount of food they consume. LOC eating is associated cross
      sectionally with greater adiposity in children and adolescents and seems to
      predispose youth to gain weight or body fat above that expected during normal
      growth, thus likely contributing to obesity in susceptible individuals. No prior
      studies have examined whether LOC eating can be decreased by interventions in
      children or adolescents without full-syndrome eating disorders or whether
      programs reducing LOC eating prevent inappropriate weight gain attributable to
      LOC eating. Interpersonal psychotherapy, a form of therapy that was designed to
      treat depression and has been adapted for the treatment of eating disorders, has
      shown efficacy in reducing binge eating episodes and inducing weight
      stabilization among adults diagnosed with binge eating disorder. In this paper,
      we propose a theoretical model of excessive weight gain in adolescents at high
      risk for adult obesity who engage in LOC eating and associated overeating
      patterns. A rationale is provided for interpersonal psychotherapy as an
      intervention to slow the trajectory of weight gain in at-risk youth, with the aim
      of preventing or ameliorating obesity in adulthood.

PMID- 17557974
TI  - Factors affecting prevalence of overweight among 12- to 17-year-old urban
      adolescents in Hyderabad, India.
AB  - OBJECTIVE: The problem of overweight and obesity is not confined only to
      developed countries but is also widely prevalent in developing countries. The
      objective of this study was to assess the prevalence of overweight and obesity as
      defined by the International Obesity Task Force (IOTF) among school-age children
      in Hyderabad, India, and identify its associated factors. RESEARCH METHODS AND
      PROCEDURES: A cross-sectional and institutional study, adopting a multistage
      stratified cluster sampling procedure, was carried out during 2003 on adolescents
      12 to 17 years of age of both sexes from Hyderabad, India. RESULTS: The overall
      prevalence of overweight was 6.1% [95% confidence interval (CI): 4.2, 8.0] among
      boys and 8.2% among girls (CI: 6.0, 10.4); 1.6% and 1.0% were obese,
      respectively. The prevalence was significantly higher (p < 0.05) among
      adolescents who watched television > or =3 h/d (10.4%) or belonged to a high
      socioeconomic background (14.9%, p < 0.001), whereas it was significantly lower
      among those participating regularly in outdoor games > or =6 h/wk (3.1%, p <
      0.004) and household activities > or =3 h/d (4.7%, p < 0.001). The logistic
      regression analysis revealed that the prevalence of overweight was 4 times higher
      among the adolescents of high socioeconomic status [odds ratio (OR): 4.1; CI:
      2.25, 7.52], 3 times higher in those not participating in outdoor games (OR:
      2.75; CI: 1.56, 4.72), and 1.92 times higher in those watching television > or =3
      h/d (OR: 1.92; CI: 1.16, 3.18). DISCUSSION: This study confirmed the findings of
      earlier studies carried out in Western countries and emphasizes that regular
      physical exercise, doing household activities, regulated television viewing, and
      healthy eating behaviors could contribute to controlling overweight and obesity.

PMID- 17557975
TI  - Immigration and obesity among lower income blacks.
AB  - OBJECTIVE: Our objective was to examine the associations of nativity, immigrant
      generation, and language acculturation with obesity among lower income black
      adult men and women. RESEARCH METHODS AND PROCEDURES: Data from 551 black adult
      men and women were collected from participants in the Healthy Directions-Health
      Centers Study. Race/ethnicity and nativity were self-reported. Language
      acculturation was defined using participants' first language, preferred reading
      language, and language spoken at home. Mixed model logistic regression models
      were estimated to account for within-health center clustering. RESULTS: Foreign
      born blacks had a lower obesity risk, compared with all U.S.-born participants,
      in multivariable analyses [odds ratio (OR) = 0.57, 95% confidence interval (CI),
      0.38, 0.84]. Among U.S.-born participants, those with foreign-born parents were
      significantly less likely to be obese than individuals with U.S.-born parents (OR
      = 0.54; 95% CI, 0.37, 0.80). Low-moderate language acculturation also decreased
      the odds of being obese (OR = 0.45; 95% CI, 0.23, 0.88). DISCUSSION: Our findings
      suggest a protective effect of foreign-born status and low-moderate language
      acculturation on obesity risk among lower income black immigrants. These data
      highlight the importance of more frequently examining nativity in obesity-related
      research conducted among blacks.

PMID- 17557976
TI  - Endothelial activation markers and their key regulators after restrictive
      bariatric surgery.
AB  - OBJECTIVE: Increased plasma levels of endothelial activation markers in obese
      subjects reflect the positive association between cardiovascular diseases and
      obesity. The pro-inflammatory state associated with obesity is thought to play a
      major role in endothelial cell activation in severely obese individuals. Previous
      studies demonstrated that long-term weight loss after bariatric surgery is
      accompanied by a decreased proinflammatory state. However, little is known about
      the long-term effects of bariatric surgery on endothelial cell activation.
      RESEARCH METHODS AND PROCEDURES: Plasma levels of soluble intercellular adhesion
      molecule-1 (sICAM-1), soluble endothelial selectin (sE-selectin), and soluble
      vascular cell adhesion molecule-1 (sVCAM-1), all markers of endothelial cell
      activation, and of their regulators adiponectin and resistin were measured at
      different time-points postoperatively in 26 consecutive patients who underwent
      restrictive surgery, with a follow-up of 2 years. RESULTS: During the first 6
      months after bariatric surgery, sE-selectin levels decreased. Despite substantial
      weight loss, sICAM-1 and sVCAM-1 plasma levels did not decrease significantly.
      After 24 months, sICAM-1 levels were significantly decreased, whereas sE-selectin
      levels were further decreased. However, sVCAM-1 levels remained elevated.
      Adiponectin levels did not change significantly during the first 6 months after
      bariatric surgery, whereas resistin levels increased. After 24 months,
      adiponectin levels were similar to normal-weight controls, but resistin levels
      remained high. DISCUSSION: Reductions in plasma levels of different markers of
      endothelial activation after bariatric surgery show different temporal patterns,
      suggesting that distinct mechanisms are involved in their regulation. Although
      not all endothelial activation markers normalize after bariatric surgery, our
      findings suggest that bariatric surgery can reduce endothelial activation in the
      long term.

PMID- 17557977
TI  - The F box protein S phase kinase-associated protein 2 regulates adipose mass and
      adipocyte number in vivo.
AB  - OBJECTIVE: The etiology of some obesity may involve adipocyte hyperplasia.
      However, the role of adipocyte number in establishing adipose mass is unclear.
      Cyclin-dependent kinase inhibitor p27 regulates activity of cyclin/cyclin
      dependent kinase complexes responsible for cell cycle progression. This protein
      is critical for establishing adult adipocyte number, and p27 knockout increases
      adult adipocyte number. The SCF (for Skp1-Cullin-F-box protein) complex targets
      proteins such as p27 for ubiquitin-proteosome degradation; the F box protein S
      phase kinase-associated protein 2 (Skp2), a component of the SCF complex,
      specifically recognizes p27 for degradation. We used Skp2 knockout (Skp2(-/-))
      mice to test whether Skp2 loss decreased adipose mass and adipocyte number.
      RESEARCH METHODS AND PROCEDURES: We measured body weight, adipose mass, adipocyte
      diameter and number, and glucose tolerance in wild-type (WT), Skp2(-/-), and p27(
      /-)Skp2(-/-) mice. Mouse embryo fibroblasts (MEFs) from WT and Skp2(-/-) fetuses
      were differentiated to determine whether Skp2 directly affected adipogenesis.
      RESULTS: Skp2(-/-) mice had a 50% decrease in both subcutaneous and visceral fat
      pad mass and adipocyte number; these decreases exceeded those in body weight,
      kidney, or muscle. To test the hypothesis that Skp2 effects on adipocyte number
      involved p27 accumulation, we used p27(-/-)Skp2(-/-) double knockout mice. The
      Skp2(-/-) decrements in adipocyte number and fat pad mass were totally reversed
      in p27(-/-)Skp2(-/-) mice. Adipogenesis was inhibited in MEFs from Skp2(-/-) vs.
      WT mice, and this inhibition was absent in MEFs from p27(-/-)Skp2(-/-) mice.
      DISCUSSION: Our results indicate that Skp2 regulates adipogenesis and ultimate
      adipocyte number in vivo; thus, Skp2 may contribute to obesity involving
      adipocyte hyperplasia.

PMID- 17557978
TI  - Sleep apnea is induced by a high-fat diet and reversed and prevented by metformin
      in non-obese rats.
AB  - OBJECTIVE: We assessed the relationship between a high-fat (HF) diet and central
      apnea during rapid eye movement and non-rapid eye movement sleep stages by
      recording ventilatory parameters in 28 non-obese rats in which insulin resistance
      had been induced by an HF diet. We also studied whether metformin (an anti
      hyperglycemic drug frequently used to treat insulin resistance) could reverse
      sleep apnea or prevent its occurrence in this experimental paradigm. RESEARCH
      METHODS AND PROCEDURES: Rats were fed with a standard diet (10 rats), an HF diet
      (8 rats), or an HF diet concomitantly with metformin treatment (10 rats). Each
      animal was instrumented for electroencephalographic and electromyographic
      recording. After 3 weeks, ventilatory parameters during sleep were recorded with
      a body plethysmograph. All rats were treated with metformin for 1 week, after
      which time the ventilatory measurements were measured again. RESULTS: Our results
      showed that the three groups of animals did not differ in terms of body growth
      over the entire experimental period. The HF diet did not modify sleep structure
      or minute ventilation in the different sleep stages. A great increase (+266 +/-
      48%) in central apnea frequency was observed in insulin-resistant rats. This was
      explained by an increase in both post-sigh (+195 +/- 35%) and spontaneous apnea
      (+437 +/- 65%) in the different sleep stages. These increases were suppressed by
      metformin treatment. DISCUSSION: Insulin resistance induced by the HF diet could
      be the promoter of sleep apnea in non-obese rats. Metformin is an efficient
      curative and preventive treatment for sleep apnea, suggesting that insulin
      resistance modifies the ventilatory drive independently of obesity.

PMID- 17557979
TI  - Reduced adiposity in ob/ob mice following total body irradiation and bone marrow
      transplantation.
AB  - OBJECTIVE: The objective of this study was to assess long-term metabolic
      consequences of total body irradiation (TBI) and bone marrow transplantation.
      Severe obesity develops due to both hypertrophy and hyperplasia of adipocytes. We
      hypothesized that TBI would arrest adipose tissue growth and would affect insulin
      resistance (IR). RESEARCH METHODS AND PROCEDURES: We exposed 2-month-old female
      ob/ob mice to 8 Grays of TBI followed by bone marrow transplantation and tested
      the animals for body weight (BW) gain, body composition, blood glucose, and
      insulin sensitivity. RESULTS: Two months after TBI, irradiated mice stopped
      gaining BW, whereas non-treated mice continued to grow. At the age of 9.5 months,
      body mass of irradiated mice was 60.6 +/- 1.4 grams, which was only 61% of that
      in non-treated ob/ob controls (99.4 +/- 1.6 grams). Body composition measurements
      by DXA showed that decreased BW was primarily due to an impaired fat
      accumulation. This could not result from the production of leptin by bone marrow
      derived adipocyte progenitors because inhibition of the obese phenotype was
      identical in recipients of both B6 and ob/ob bone marrow. Inability of the
      irradiated mice to accumulate fat was associated with hepatomegaly, lower levels
      of monocyte chemoattractant protein-1 expression in adipose tissue, and increased
      IR. DISCUSSION: Our data argue in favor of the hypothesis that inability of
      adipose tissue to expand may increase IR. This mouse model may be valuable for
      studies of late-onset radiation-induced IR in humans.

PMID- 17557980
TI  - Inhibition of the actions of peroxisome proliferator-activated receptor alpha on
      obesity by estrogen.
AB  - OBJECTIVE: To determine whether the major ovarian factor estrogen modulates
      peroxisome proliferator-activated receptor (PPAR) alpha actions on obesity and to
      investigate the mechanism by which estrogen regulates PPARalpha actions. RESEARCH
      METHODS AND PROCEDURES: Female ovariectomized mice were randomly divided into
      four groups (n = 8/group). After they were treated with combinations of high fat,
      fenofibrate (FF), or 17beta-estradiol (E) for 13 weeks, variables and
      determinants of obesity and lipid metabolism were measured using in vivo and in
      vitro approaches. RESULTS: When female ovariectomized mice were given a high-fat
      diet with either FF or E, body weight gain and white adipose tissue mass were
      significantly reduced and serum lipid profiles were improved compared with
      control mice fed a high-fat diet alone. When mice were concomitantly treated with
      FF and E, however, E reversed the effects of FF on body weight gain, serum lipid
      profiles, and hepatic PPARalpha target gene expression. Consistent with the in
      vivo data, E not only decreased basal levels of PPARalpha reporter gene
      activation but also significantly decreased Wy14,643-induced luciferase reporter
      activity. In addition, inhibition of PPARalpha functions by E did not seem to
      occur by interfering with the DNA binding of PPARalpha. DISCUSSION: Our results
      demonstrate that in vivo and in vitro treatment of estrogen inhibited the actions
      of FF-activated PPARalpha on obesity and lipid metabolism through changes in the
      expression of PPARalpha target genes, providing evidence that FF does not
      regulate obesity in female mice with functioning ovaries.

PMID- 17557981
TI  - Visceral and subcutaneous adiposity measurements in adults: influence of
      measurement site.
AB  - OBJECTIVE: Excess abdominal adiposity is a known risk factor for cardiovascular
      diseases. Computed tomography can be used to examine the visceral (VAT) and
      subcutaneous (SAT) components of abdominal adiposity, but it is unresolved
      whether single-slice or multi-slice protocols are needed. RESEARCH METHOD AND
      PROCEDURES: Nine computed tomography scans were obtained in the lumbar spine
      region of 24 adults. The nine slices were obtained at three intervertebral
      positions (L2-L3, L3-L4, and L4-L5) and at 7 mm above and below these locations.
      Intra-site and inter-site differences in SAT, VAT, total adipose tissue, and the
      VAT/SAT ratio were examined using ANOVA and confidence intervals for pairwise
      differences between means. RESULTS: Intervertebral SAT values increased from
      103.1 +/- 50.9 (standard deviation) cm(2) at L2-L3 to 153.3 +/- 68.8 cm(2) at L4
      L5, whereas the corresponding VAT values decreased from 164.3 +/- 125.4 to 126.0
      +/- 82.7 cm(2). The VAT/SAT ratio was not constant, decreasing from 1.8 +/- 1.4
      to 0.9 +/- 0.7. Repeated-measures ANOVA indicated significant inter- and intra
      site differences (p </= 0.02) for SAT, VAT, and the VAT/SAT ratio at L3-L4 and L4
      L5 (p < 0.001). DISCUSSION: These differences show the limitation of using a
      single-slice assessment of abdominal fat distribution, both for a subject and
      between subjects. Furthermore, the sizeable differences in the intra-site scans
      indicate that precise repositioning is needed for longitudinal studies. In
      summary, our findings suggest that a multi-site imaging protocol may provide a
      more complete assessment of abdominal fat stores and distribution than use of a
      single site.

PMID- 17557982
TI  - Biliopancreatic diversion reduces QT interval and dispersion in severely obese
      patients.
AB  - OBJECTIVES: The objectives were to evaluate QT interval (QTc) and QT-interval
      dispersion (QTd) in severely obese individuals and to determine the effects of
      biliopancreatic diversion (BPD) and weight loss after BPD on ventricular
      repolarization parameters. BACKGROUND: People with severe obesity (SO) have a 50%
      to 100% increased risk of death associated with a 1.6-fold increased risk of
      sudden death. BPD surgery induces rapid and considerable weight loss through
      severe lipid malabsorption, thus achieving long-term weight control. RESEARCH
      METHODS AND PROCEDURES: A total of 85 subjects with SO (age, 42 +/- 12 years; 66
      females; mean body weight, 120 +/- 29 kg; BMI, 45 +/- 11 kg/m(2)) of 330 who had
      a bariatric surgical consultation between January 2001 and July 2002 were
      enrolled. Inclusion criteria were sinus rhythm, unremarkable 12 leads surface
      electrocardiogram, no atrioventricular blocks and/or bundle branch blocks, normal
      serum electrolyte profile, and no medical therapies exerting known effects on
      QTc. Exclusion criteria were previous diagnosis of coronary artery disease, known
      cardiovascular disease, atrial fibrillation or any other known cardiac
      arrhythmias, cancer, or renal dysfunction. RESULTS: A total of 86% of patients
      had QTc >440 ms and/or QTd >60 ms. Subjects with SO showed a mean maximum QTc of
      446 +/- 28 ms and a mean QTd of 52 +/- 20 ms. A close correlation was found
      between QTc and QTd (p < 0.0001; R(2) = 0.33). One month after BPD, mean QTc was
      420 ms and remained stable at follow-up; QTd was 32 ms at 1 and 6 months and
      became 35 ms at 1 year. CONCLUSIONS: Ventricular repolarization abnormalities are
      significantly increased in subjects with SO. Reduction of QT abnormalities after
      BPD is independent of weight loss and is caused by the 100% reduction of glucose
      plasma shortly after surgery. This effect may be related to surgical interruption
      of the entero-insular axis.

PMID- 17557983
TI  - Weight loss and health outcomes in African Americans and whites after gastric
      bypass surgery.
AB  - OBJECTIVE: The objective was to describe differences in weight loss, dietary
      intake, and cardiovascular risk factors between white and African-American
      patients after gastric bypass (GBP). RESEARCH METHODS AND PROCEDURES: This was a
      retrospective database review of a sample of 84 adult patients (24 African
      American and 60 white women and men) between the ages of 33 and 53 years. All
      subjects had GBP surgery in 2001 at the Bariatric Surgery Program at Boston
      Medical Center in Boston, MA, and were followed for one year postoperatively.
      Patients were excluded if weight data were missing at baseline, 3 months, or 1
      year after GBP. A total of 9 African Americans and 41 whites provided data at all
      3 time-points and were included in the study. Differences in weight loss, diet,
      and cardiovascular risk factors were analyzed. RESULTS: There were no differences
      in baseline characteristics between African Americans and whites. Mean weight
      loss for the entire sample was 36 +/- 9%, with a range of 8% to 54% relative to
      initial body weight. Whites lost more weight (39 +/- 8%) than African Americans
      (26 +/- 10%) (p < 0.05). Dietary parameters, as well as improvements in blood
      pressure and lipid profiles, were similar in the two racial groups. DISCUSSION:
      Differences in weight loss between severely obese African Americans and whites
      undergoing open GBP are unlikely to be related to postoperative dietary
      practices. Our data are consistent with previous reports implicating metabolic
      differences between the two racial groups.

PMID- 17557984
TI  - Sibutramine plus meal replacement therapy for body weight loss and maintenance in
      obese patients.
AB  - OBJECTIVE: Our objective was to assess the efficacy and safety of sibutramine
      with a low-calorie diet (LCD) and commercial meal-replacement product in
      achieving weight loss and weight-loss maintenance in obese patients. RESEARCH
      METHODS AND PROCEDURES: Eight U.S. centers recruited 148 obese patients for a 3
      month comprehensive weight-loss therapy (Phase I) comprising daily sibutramine 10
      mg + LCD (two Slim-Fast meal-replacement shakes, one low-calorie meal; total
      kcal/d = 1200-1500). Patients (N = 113) who lost > or =5% of initial body weight
      during Phase I were randomized for a 9-month period (Phase II) to daily
      sibutramine 15 mg + LCD (one meal-replacement shake; two low-calorie meals: total
      kcal/d approximately 1200-1500) or daily placebo + three low-calorie meals (total
      kcal/d approximately 1200-1500). Both phases included behavior modification.
      Efficacy was assessed by body weight change during each phase and by the number
      of patients at endpoint maintaining > or =80% of the weight they had lost by the
      end of Phase I. Other outcomes included changes in cardiovascular and metabolic
      risk factors, adverse events, and vital signs. RESULTS: Mean body weight change
      during Phase I was -8.3 kg (p < 0.001). Patients randomized to sibutramine in
      Phase II had an additional -2.5 kg mean weight loss vs. a 2.8-kg increase in the
      placebo group (p < 0.001). More sibutramine patients maintained > or =80% of
      their Phase I weight loss at the end of Phase II (85.5% vs. placebo 36.7%, p <
      0.001). Most adverse events were mild or moderate in severity, and all serious
      adverse events were unrelated to sibutramine. DISCUSSION: Sibutramine plus LCD
      with meal replacements and behavior modification is a safe and effective strategy
      for achieving and sustaining weight loss in obese patients.

PMID- 17557985
TI  - A green tea extract high in catechins reduces body fat and cardiovascular risks
      in humans.
AB  - OBJECTIVE: The body fat reducing effect and reduction of risks for cardiovascular
      disease by a green tea extract (GTE) high in catechins was investigated in humans
      with typical lifestyles. RESEARCH METHODS AND PROCEDURES: Japanese women and men
      with visceral fat-type obesity were recruited for the trial. After a 2-week diet
      run-in period, a 12-week double-blind parallel multicenter trial was performed,
      in which the subjects ingested green tea containing 583 mg of catechins (catechin
      group) or 96 mg of catechins (control group) per day. Randomization was
      stratified by gender and body mass index at each medical institution. The
      subjects were instructed to maintain their usual dietary intake and normal
      physical activity. RESULTS: Data were analyzed using per-protocol samples of 240
      subjects (catechin group; n = 123, control group; n = 117). Decreases in body
      weight, body mass index, body fat ratio, body fat mass, waist circumference, hip
      circumference, visceral fat area, and subcutaneous fat area were found to be
      greater in the catechin group than in the control group. A greater decrease in
      systolic blood pressure (SBP) was found in the catechin group compared with the
      control group for subjects whose initial SBP was 130 mm Hg or higher. Low-density
      lipoprotein (LDL) cholesterol was also decreased to a greater extent in the
      catechin group. No adverse effect was found. DISCUSSION: The continuous ingestion
      of a GTE high in catechins led to a reduction in body fat, SBP, and LDL
      cholesterol, suggesting that the ingestion of such an extract contributes to a
      decrease in obesity and cardiovascular disease risks.

PMID- 17557986
TI  - Heritability of hyperphagic eating behavior and appetite-related hormones among
      Hispanic children.
AB  - OBJECTIVE: Eating in the absence of hunger (EAH) may be a genetically influenced
      phenotype of overweight children, but evidence is limited. This research
      evaluated the heritability (h(2)) of EAH and its association with overweight
      among Hispanic children 5 to 18 years old. Genetic and environmental associations
      of EAH with overweight, fat mass, and key hormonal regulators of food intake were
      also evaluated. RESEARCH METHODS AND PROCEDURES: A family design was used to
      study 801 children from 300 Hispanic families. Weighed food intakes were used to
      measure EAH after an ad libitum dinner providing 50% of estimated energy needs.
      Fasting ghrelin, amylin, insulin, and leptin were measured by immunoassays.
      Measured heights, weights, and fat mass (using DXA) were obtained. Total energy
      expenditure (TEE) was measured by room respiration calorimetry. RESULTS: On
      average, children consumed 41% of TEE at the dinner meal, followed by an
      additional 19% of TEE in the absence of hunger. Overweight children consumed 6.5%
      more energy at dinner (p < 0.001) and 14% more energy in the absence of hunger (p
      < 0.001) than non-overweight children. Significant heritabilities were seen for
      EAH (h(2) = 0.51) and dinner intake (h(2) = 0.52) and for fasting levels of
      ghrelin (h(2) = 0.67), amylin (h(2) = 0.37), insulin (h(2) = 0.37), and leptin
      (h(2) = 0.34). Genetic correlations were seen between eating behavior and fasting
      hormones, suggesting common underlying genes affecting their expression.
      DISCUSSION: This research provides new evidence that overweight Hispanic children
      exhibit elevated levels of hyperphagic eating behaviors that are influenced by
      genetic endowment.

PMID- 17557987
TI  - Exercise effect on weight and body fat in men and women.
AB  - OBJECTIVES: The effect of national exercise recommendations on adiposity is
      unknown and may differ by sex. We examined long-term effects of aerobic exercise
      on adiposity in women and men. RESEARCH METHODS AND PROCEDURES: This was a 12
      month randomized, controlled clinical trial testing exercise effect on weight and
      body composition in men (N = 102) and women (N = 100). Sedentary/unfit persons,
      40 to 75 years old, were recruited through physician practices and media. The
      intervention was facility- and home-based moderate-to-vigorous intensity aerobic
      activity, 60 min/d, 6 days/wk vs. controls (no intervention). RESULTS: Exercisers
      exercised a mean 370 min/wk (men) and 295 min/wk (women), and seven dropped the
      intervention. Exercisers lost weight (women, -1.4 vs. +0.7 kg in controls, p =
      0.008; men, -1.8 vs. -0.1 kg in controls, p = 0.03), BMI (women, -0.6 vs. +0.3
      kg/m(2) in controls, p = 0.006; men, -0.5 kg/m(2) vs. no change in controls, p =
      0.03), waist circumference (women, -1.4 vs. +2.2 cm in controls, p < 0.001; men, 
      3.3 vs. -0.4 cm in controls, p = 0.003), and total fat mass (women, -1.9 vs. +0.2
      kg in controls, p = 0.001; men, -3.0 vs. +0.2 kg in controls, p < 0.001).
      Exercisers with greater increases in pedometer-measured steps per day had greater
      decreases in weight, BMI, body fat, and intra-abdominal fat (all p trend < 0.05
      in both men and women). Similar trends were observed for increased minutes per
      day of exercise and for increases in maximal oxygen consumption. DISCUSSION:
      These data support the U.S. Department of Agriculture and Institute of Medicine
      guidelines of 60 min/d of moderate-to-vigorous physical activity.

PMID- 17557988
TI  - Physical activity levels of normal-weight and overweight girls and boys during
      primary school recess.
AB  - OBJECTIVE: This study aimed to compare moderate-to-vigorous physical activity
      (MVPA) and vigorous physical activity (VPA) in normal-weight and overweight boys
      and girls during school recess. RESEARCH METHODS AND PROCEDURES: Four hundred
      twenty children, age 6 to 10 years, were randomly selected from 25 schools in
      England. Three hundred seventy-seven children completed the study. BMI was
      calculated from height and weight measurements, and heart rate reserve thresholds
      of 50% and 75% reflected children's engagement in MVPA and VPA, respectively.
      RESULTS: There was a significant main effect for sex and a significant
      interaction between BMI category and sex for the percent of recess time spent in
      MVPA and VPA. Normal-weight girls were the least active group, compared with
      overweight boys and girls who were equally active. Fifty-one boys and 24 girls of
      normal weight achieved the 40% threshold; of these, 30 boys and 10 girls exceeded
      50% of recess time in MVPA. Eighteen overweight boys and 22 overweight girls
      exceeded the 40% threshold, whereas 8 boys and 8 girls exceeded the 50%
      threshold. DISCUSSION: Overweight boys were significantly less active than their
      normal-weight male counterparts; this difference did not hold true for girls.
      Even though nearly double the number of normal-weight children achieved the 40%
      of MVPA during recess compared with overweight children, physical activity
      promotion in school playgrounds needs to be targeted not only at overweight but
      at other health parameters, as 40 overweight children met the 40% MVPA target
      proposed for recess.

PMID- 17557989
TI  - Effect of increased dairy consumption on appetitive ratings and food intake.
AB  - OBJECTIVE: The influence of dairy product consumption on food intake and
      appetitive sensations was explored in a cross-over design study with individuals
      who were habitually low (<1 serving/d) or high (>3 servings/d) dairy consumers.
      RESEARCH METHODS AND PROCEDURES: Fifty-eight participants were required to eat
      one portion of dairy each day (low dairy) or three portions of dairy each day
      (high dairy) for 7 days. After a 7-day washout period, the opposite treatment
      condition was completed. Food intake and appetitive ratings were measured on each
      day of the treatment periods. RESULTS: During the high-dairy period, participants
      consumed 209 kcal/d more than during the low dairy period (p < 0.05). There were
      no significant differences in subjective appetite ratings. Habitual dairy use did
      not influence either the appetitive or dietary findings. DISCUSSION: These data
      indicate that increasing dairy consumption may lead to increased energy intake,
      which could potentially cause weight gain.

PMID- 17557990
TI  - Does a high-protein diet improve weight loss in overweight and obese children?
AB  - OBJECTIVE: To evaluate the effect of a high-protein diet on anthropometry, body
      composition, subjective appetite, and mood sensations in overweight and obese
      children attending a residential weight-loss camp. RESEARCH METHODS AND
      PROCEDURES: Children (120; BMI, 33.1 +/- 5.5 kg/m(2); age, 14.2 +/- 1.9 years)
      were randomly assigned to either a standard or high-protein diet group (15% vs.
      22.5% protein, respectively). All children were assessed at baseline and at the
      end of the camp for anthropometry, body composition, blood pressure, biochemical
      variables (n = 27), and subjective appetite and mood sensations (n = 50).
      RESULTS: Attendance at the weight-loss camp resulted in significant improvements
      in most measures. Campers lost 5.5 +/- 2.9 kg in body weight (p < 0.001) and 3.8
      +/- 5.4 kg in fat mass (p < 0.001) and reduced their BMI standard deviation score
      by 0.27 +/- 0.1 (p < 0.001) and their waist circumference by 6.6 +/- 2.8 cm (p <
      0.001). Subjective sensations of hunger increased significantly over the camp
      duration, but no other changes in appetite or mood were observed. There were no
      significant differences between the two diets on any physical or subjective
      measures. DISCUSSION: Weight-loss camps are effective in assisting children to
      lose weight and improve on a range of health outcomes, independently of the
      protein content of the diet. The implications of an increase in hunger associated
      with weight loss needs to be considered. Further work is warranted to investigate
      whether higher levels of dietary protein are feasible or effective in longer-term
      weight-loss interventions of this type.

PMID- 17557991
TI  - The effect of large portion sizes on energy intake is sustained for 11 days.
AB  - OBJECTIVE: A previous study showed that increasing the portion sizes of all foods
      led to an increase in energy intake that was sustained over 2 days. The objective
      of the present study was to determine whether participants would compensate for
      excess energy intake or continue to overeat when portion sizes were increased for
      11 days. RESEARCH METHODS AND PROCEDURES: Participants in the study were 23
      normal-weight and overweight participants (10 women and 13 men). All of their
      foods and caloric beverages were provided during two different periods of 11
      consecutive days, which were separated by a 2-week interval. During one period,
      standard portions of all items were served; during the other, all portion sizes
      were increased by 50%. RESULTS: The 50% increase in portion sizes resulted in a
      mean increase in daily energy intake of 423 +/- 27 kcal (p < 0.0001), which did
      not differ significantly between women and men. This increase was sustained for
      11 days and did not decline significantly over time, leading to a mean cumulative
      increase in intake of 4636 +/- 532 kcal. A significant effect of portion size on
      intake was seen at all meals and in all categories of foods except fruit (as a
      snack) and vegetables. The effect of portion size on intake was not influenced by
      the body weight status of participants. DISCUSSION: These results strengthen the
      evidence suggesting that increased portions contribute to the overconsumption of
      energy and to excess body weight.

PMID- 17557992
TI  - Parent overweight predicts daughters' increase in BMI and disinhibited overeating
      from 5 to 13 years.
AB  - OBJECTIVE: To assess whether parental overweight status and disinhibited
      overeating are predictive of daughters' accelerated weight gain and disinhibited
      overeating. RESEARCH METHODS AND PROCEDURES: Participants were part of a
      longitudinal study of girls (N = 197) and their parents. Measured height and
      weight were used to calculate BMI [weight (kilograms)/height (meters)(2)].
      Parents' disinhibited eating behavior was assessed using the Eating Inventory.
      Girls' disinhibited eating was assessed using a behavioral protocol to measure
      eating in the absence of hunger. Girls were classified based on parental
      overweight at study entry into four groups: neither, mother only, father only, or
      both parents overweight. RESULTS: Girls with both parents overweight had the most
      rapid increases in BMI from 5 to 13 years of age; BMI increased most slowly among
      the neither parent overweight group, with intermediate increases in BMI among
      mother only and father only overweight groups. Daughters with both parents
      overweight at study entry were eight times more likely to be overweight at age
      13, controlling for daughters' weight at age 5. Girls with both parents
      overweight had higher levels of disinhibited eating across all ages than all
      other groups. Although girls in all parental weight status groups showed
      increases in disinhibited eating over time, girls with both parents overweight
      had larger increases in disinhibited eating over time compared with all other
      groups. DISCUSSION: Girls growing up in families differing in parental overweight
      had divergent developmental trajectories for BMI and disinhibited overeating.
      Findings reveal the need to focus prevention efforts on overweight parents of
      young children.

PMID- 17557993
TI  - BMI, obesity, and sickness absence in the Whitehall II study.
AB  - OBJECTIVE: To study BMI and change in BMI from age 25 as predictors of sickness
      absence. RESEARCH METHODS AND PROCEDURES: Data were collected from 2564 women and
      5853 men, who were British civil servants (35 to 55 years) on entry to the
      Whitehall II study (Phase 1, 1985 to 1988). Employer's records provided annual
      medically certified (long, >7 days) and self-certified (short, 1 to 7 days)
      spells of sickness absence. BMI at age 25 and Phase 1 were examined in relation
      to absences from Phase 1 to the end of 1998 (mean follow-up, 7.0 years). RESULTS:
      After adjustment for employment grade, health-related behaviors, and health
      status, overweight (BMI = 25.0 to 29.9 kg/m(2)) and obesity (BMI > 30.0 kg/m(2))
      at Phase 1 were significant predictors of short and long absences in both sexes;
      rate ratios (95% confidence intervals) ranged from 1.13 (1.05 to 1.21) to 1.51
      (1.30 to 1.76) compared with a BMI of 21.0 to 22.9 kg/m(2). Additionally, a BMI
      of 23.0 to 24.9 kg/m(2) at Phase 1 predicted long absences in women, and
      underweight (BMI < 21.0 kg/m(2)) predicted short absences in men. Obesity at age
      25 predicted long absences, and obesity at Phase 1 predicted short and long
      absences in both sexes. Chronic obesity was a particularly strong predictor of
      long absences in men, with a rate ratio of 2.61 (1.88 to 3.63). DISCUSSION:
      Findings from this well-characterized cohort suggest that the obesity epidemic in
      industrialized countries may result in significant increases in sickness absence.
      Further research is needed to determine the underlying mechanisms. Policy to
      reduce sickness absence needs to tackle the problem of excess weight in the
      working population.

PMID- 17557994
TI  - Hispanic and Asian pubertal girls have higher android/gynoid fat ratio than
      whites.
AB  - OBJECTIVE: To examine differences in body size, composition, and distribution of
      body fat among Hispanic, white, and Asian adolescents. RESEARCH METHODS AND
      PROCEDURES: This included cross-sectional data from the baseline sample of the
      Adequate Calcium Today trial. Participants included 180 Asian, 234 Hispanic, and
      325 white girls 11.8 +/- 0.05 years of age from Arizona, California, Hawaii,
      Indiana, Ohio, and Nevada. Anthropometric and DXA measurements (Lunar Prodigy)
      were standardized across sites. Tanner pubertal stage was self-selected from line
      drawings. Physical activity was assessed by a validated questionnaire.
      Comparisons between ethnic groups were examined using contrasts in the context of
      a general linear model. RESULTS: Controlling for pubertal stage and study site
      only, Asians weighed less than Hispanics and were shorter than Hispanics and
      whites. Controlling for pubertal stage, height, weight, and study site, Asians
      had shorter leg lengths, smaller waist circumference, longer trunk lengths, more
      lean mass, less total fat mass, and less gynoid fat mass than Hispanics and
      whites; Asians had larger bitrochanteric width than whites; Asians had smaller
      DXA-derived android fat mass than Hispanics; and whites had smaller mean
      android/gynoid fat ratio than Hispanics. However, whites had a smaller
      android/gynoid fat ratio than both Asians and Hispanics in a model that adjusted
      for ethnicity, pubertal stage, bitrochanteric width, waist circumference, trunk
      length, log of physical activity, and study site, which explained 77% of the
      variation. DISCUSSION: Ethnic differences in fat distribution are partially
      explained by differences in skeletal dimensions.

PMID- 17557995
TI  - Adult obesity does not predict 6-year weight gain in men: the Aerobics Center
      Longitudinal Study.
AB  - OBJECTIVE: To determine the longitudinal relation between history of adult
      obesity and the 6-year trajectory of weight change in men. RESEARCH METHODS AND
      PROCEDURES: Subjects were healthy, affluent men (n = 761) between the ages of 20
      and 78 years who completed at least four comprehensive medical exams at the
      Cooper Clinic between 1987 and 2003. Maximum adult weight was reported, and
      current height was measured at baseline. Body weight and cardiorespiratory
      fitness were measured at all examinations. Adult obesity status was determined
      from self-reported maximum weight and measured height at baseline as BMI > or =
      30 kg/m(2). Weight at all examinations was regressed on a history of adult
      obesity using linear mixed effects modeling. RESULTS: At baseline, men reporting
      a history of adult obesity were significantly heavier than men reporting no such
      history (BMI 29.8 vs. 25.0 kg/m(2); p < 0.05). However, the rate of weight gain
      among men with a history of obesity was slower than among men without a history
      of adult obesity (0.04 vs. 0.18 kg/yr; p = 0.09), although this difference was
      only marginally significant. Fitness modulated the relationship between history
      of obesity and weight change over time, and both higher levels of fitness and
      greater frequency of dieting were associated with attenuated weight gain. In
      contrast, chronic disease and depression were associated with accelerated weight
      gain. DISCUSSION: Although a history of obesity was associated with higher
      weight, it did not seem to result in accelerated weight gain over time.
      Additionally, dieting and fitness were important for minimizing weight gain.

PMID- 17557996
TI  - Sedentary behavior, recreational physical activity, and 7-year weight gain among
      postmenopausal U.S. women.
AB  - OBJECTIVE: To assess the relationship among recreational physical activity (PA),
      non-occupational sedentary behavior, and 7-year weight gain among postmenopausal
      U.S. women 40 to 69 years old. RESEARCH METHODS AND PROCEDURES: In 1992 and 1999,
      18,583 healthy female participants from the Cancer Prevention Study II Nutrition
      Cohort completed questionnaires on anthropometric characteristics and lifestyle
      factors. The associations between recreational PA [in metabolic equivalent (MET)
      hours per week] and non-occupational sedentary behavior (in hours per day) at
      baseline and risk for 7-year weight gain (5 to 9 or >or =10 vs. +/-4 pounds) were
      assessed using multivariate logistic regression analysis. RESULTS: Neither PA nor
      sedentary behavior was associated with a 5- to 9-pound weight gain. Among women
      who were not overweight at baseline (BMI <25.0), the odds of > or =10-pound
      weight gain were 12% lower (odds ratio, 0.88; 95% confidence interval, 0.77 to
      0.99) for those in the highest category of recreational PA (> or =18 MET h/wk)
      compared with >0 to <4 MET h/wk; odds were 47% higher (odds ratio, 1.47; 95%
      confidence interval, 1.21 to 1.79) for non-overweight women who reported > or =6
      h/d of non-occupational sedentary behavior compared with <3 h/d. Neither PA nor
      sedentary behavior were associated with risk of > or =10-pound weight gain weight
      among women who were overweight at baseline (BMI > or =25.0). DISCUSSION: Both
      recreational PA and non-occupational sedentary behavior independently predicted
      risk of > or =10-pound weight gain among postmenopausal women who were not
      overweight at baseline. Public health messages to prevent weight gain among
      normal-weight postmenopausal women may need to focus on decreasing time spent in
      sedentary behaviors and increasing the amount of time spent on PA.

PMID- 17557997
TI  - Cardiorespiratory fitness and sedentary activities are associated with adiposity
      in adolescents.
AB  - OBJECTIVE: To determine whether physical activity, sedentary activities, and/or
      cardiorespiratory fitness are related to waist circumference in adolescents, as
      previously reported in adults. RESEARCH METHODS AND PROCEDURES: The study
      subjects were a representative sample of Spanish adolescents (N = 2859; 1357
      boys, 1502 girls; age, 13 to 18.5 years), all of whom were involved in the AVENA
      (Food and Assessment of the Nutritional Status of Adolescents) study. BMI, waist
      circumference, pubertal maturation status, and cardiorespiratory fitness were
      measured in all. Leisure-time physical activity, sedentary activities, active
      commuting to school, and socioeconomic status were assessed by self-reported
      questionnaires. RESULTS: No relationship was found between leisure-time physical
      activity and BMI or waist circumference. In contrast, and in both boys and girls
      and after adjustment for confounding variables, cardiorespiratory fitness was
      found to be inversely associated with waist circumference and BMI, independent of
      sedentary activities or physical activity (p < or = 0.001). The maximum oxygen
      consumption explained 13% of the variance in waist circumference in boys and 16%
      in girls. Sedentary activities were independently and directly related to waist
      circumference in both boys and girls (p < or = 0.05) and to BMI in boys (p < or =
      0.05). Sedentary activities explained 10% of the variance in waist circumference
      in boys and 18% in girls. The BMI-adjusted waist circumference was inversely
      correlated with cardiorespiratory fitness in overweight-obese boys (p < or =
      0.05) and showed a trend toward significance in girls (p < or = 0.1). DISCUSSION:
      Both moderate to high levels of cardiorespiratory fitness and sedentary
      activities, but not physical activity, are associated with lower abdominal
      adiposity, as measured by waist circumference.

PMID- 17557998
TI  - Birth weight is inversely associated with central adipose tissue in healthy
      children and adolescents.
AB  - OBJECTIVE: Previous studies have explored the association between birth weight
      and excess childhood body fat, but few have used precise measures of body
      composition, leading to equivocal and sometimes contradictory results. RESEARCH
      METHODS AND PROCEDURES: Subjects included 101 children who underwent DXA
      measurements between 1995 and 2000. Birth weight and gestational age were
      assessed using maternal recall. Multiple linear regression analysis was used to
      determine the relationship between birth weight and the following four outcome
      variables: total fat mass (FM), truncal fat mass (TrFM), percentage body fat
      (%BF), and TrFM adjusted for FM (TrFMadj), controlling for current weight and
      Tanner stage. RESULTS: The mean age of the children studied was 12.9 +/- 2.4
      years, and the mean birth weight reported by subjects' mothers was 3.3 +/- 0.5
      kg. The FM and TrFM were 12.8 +/- 8.7 kg and 5.1 +/- 4.1 kg, respectively, and
      the mean %BF was 22.9 +/- 10.3%. Birth weight was a significant predictor of FM
      (p = 0.02) and %BF (p = 0.038). However, birth weight adjusted for gestational
      age (BWTadj) was a significant (p = 0.03) negative predictor of TrFMadj,
      independently of race, sex, Tanner stage, and current weight. DISCUSSION: These
      results provide evidence that, even in childhood and adolescence, a higher birth
      weight is associated with higher FM and %BF, while a low birth weight is
      associated with TrFM, adjusted for FM.

PMID- 17557999
TI  - Birth weight correlates differently with cardiovascular risk factors in youth.
AB  - OBJECTIVE: Childhood obesity has become prevalent, resulting in a greater risk of
      hypertension, diabetes, and dyslipidemia. However, the relationship between these
      comorbid conditions and birth weight remains uncertain. We conducted this study
      to evaluate the relationship between birth weight and cardiovascular risk factors
      in children and adolescents. RESEARCH METHODS AND PROCEDURES: In a nationwide
      survey conducted between 1992 and 2000, all schoolchildren 6 to 18 years old with
      glucosuria, proteinuria, or microscopic hematuria in repeated urine samples were
      included and received a physical examination and blood test. Those with
      gestational age <37 weeks were excluded. We enrolled 81,538 children (51,111
      girls and 30,427 boys) and obtained their birth weights from the Taiwan Birth
      Registry. Obesity and hypertension were defined by age- and sex-specific cut
      offs. Diabetes was diagnosed if the fasting glucose was >7 mM. RESULTS: The risk
      of obesity was higher for those with birth weights > or =4000 grams [odds ratio
      (OR), 1.65] and 3543 to 3999 grams (OR, 1.28) and lower for those with birth
      weights 2601 to 2999 grams (OR, 0.90), using 3000 to 3542 grams as the reference
      group. An increased risk of diabetes was associated with both higher and lower
      birth weights, indicating a U-shaped relationship (OR, <2600 grams, 1.607; 2601
      to 2999 grams, 1.119; 3543 to 3999 grams, 1.112; > or =4000 grams, 1.661). In the
      10- to 12-year-old age group, the risk of hypertension was higher in those with
      birth weights <2600 grams (OR, 1.20). DISCUSSION: Low birth weight was associated
      with childhood diabetes. High birth weight was correlated with childhood obesity
      and diabetes. Our data indicate different relationships between birth weight and
      the development of obesity, hypertension, and diabetes in childhood.

PMID- 17558000
TI  - Low serum leptin predicts mortality in patients with chronic kidney disease stage
      5.
AB  - OBJECTIVE: Leptin, secreted from adipose tissue, regulates food intake, energy
      expenditure, and immune function. It is unknown whether leptin predicts mortality
      in patients with chronic kidney disease stage 5 on hemodialysis therapy. RESEARCH
      METHODS AND PROCEDURES: We performed a prospective cohort study of 71 patients
      with chronic kidney disease stage 5 in an outpatient hemodialysis center.
      Subjects were recruited in June 1998 and followed for 83 months. Survival was
      compared by the Kaplan-Meier method. RESULTS: After 83 months of follow-up, 48
      patients (68%) had died. Serum leptin concentrations at study entry were lower
      among all deceased patients compared with those patients who survived (5.2 +/-
      9.0 microg/L; n = 48; vs. 7.7 +/- 7.8 microg/L; n = 23; p = 0.005). Baseline
      serum leptin concentrations were significantly lower in patients who died from
      cardiovascular diseases (4.7 +/- 9.4 microg/L, n = 32) or infections (4.0 +/- 2.7
      microg/L; n = 10; each p < 0.05), but not cancer (9.4 +/- 7.9 microg/L; n = 6),
      than in survivors (7.7 +/- 7.8 microg/L; n = 23; p = 0.003). The relative risk
      for mortality in patients with serum leptin concentrations below the median (<2.6
      microg/L) compared with patients above the median was 1.96 (95% confidence
      interval, 1.01 to 3.79; p = 0.04). Survival was shorter in patients with leptin
      concentrations below the median compared with those whose leptin concentrations
      were above the median (all-cause mortality, chi(2) = 5.05; p = 0.02). DISCUSSION:
      Low serum leptin concentration is an independent predictor of mortality in
      patients with chronic kidney disease stage 5 on hemodialysis therapy.

PMID- 17558001
TI  - Abdominal fat and risk of coronary heart disease in patients with peripheral
      arterial disease.
AB  - OBJECTIVE: We investigated whether the presence of concomitant coronary heart
      disease (CHD) in patients with peripheral arterial disease (PAD) can be explained
      by intra-abdominal fat accumulation and compared different measures of adiposity
      as predictors of CHD in patients with PAD. RESEARCH METHODS AND PROCEDURES: Data
      were collected from patients enrolled in the Second Manifestations of ARTerial
      disease (SMART) study, an ongoing prospective cohort study of patients with
      manifest vascular disease or vascular risk factors at the University Medical
      Centre Utrecht. The current analysis includes 315 patients, mean age 59 +/- 10
      years, who had PAD with (n = 79) or without (n = 236) CHD. Parameters of
      adiposity were measured, and intra-abdominal fat and subcutaneous fat were
      measured ultrasonographically. Metabolic syndrome was defined according to Adult
      Treatment Panel III. RESULTS: The prevalence of metabolic syndrome was higher
      among patients with CHD (63%) than among patients without CHD (48%). All
      parameters of adiposity indicated more fat in patients with CHD, except for
      subcutaneous fat. Waist circumference was associated with 64% higher prevalence
      of CHD (confidence interval, 20% to 123%) per 1 standard deviation increase in
      waist circumference after adjustment for age and sex. The odds ratio for waist
      circumference remained virtually the same after additional adjustment for the
      components of the metabolic syndrome and smoking. DISCUSSION: An increased waist
      circumference, a crude measure of intra-abdominal fat, is associated with an
      increased risk of concomitant CHD in patients with PAD.

PMID- 17558003
TI  - Guest editorial: novel directions in wound care: hypnosis and beyond.

PMID- 17558004
TI  - A first evaluation of an educational program for health care providers in a long
      term care facility to prevent foot complications.
AB  - Patients with diabetes and chronic neurological disorders are most commonly "at
      risk" with foot problems. The identification of that population is therefore
      mandatory to prevent severe foot lesions. However, not all health care providers
      (HCPs) are involved in the screening process in institutions. The authors' aim
      was to develop and evaluate an educational program for HCP in the field of at
      risk foot. All HCPs of the Loex Hospital (Department of Rehabilitation and
      Geriatrics, University Hospitals of Geneva) participated in a longitudinal
      prospective study. Different professions of HCP (doctors, nurses, nursing aides,
      physiotherapists, occupational therapists, speech-language therapists, and
      psychologists) attended a structured educational program during a 1-year period
      based on a specific consultation that the authors developed. During the sessions,
      risk factors and therapeutic and preventive interventions are discussed with both
      the patient and care givers. A questionnaire was developed and used to evaluate
      (1) initial knowledge of HCP in the field of at-risk foot and (2) the impact of
      the program on the knowledge of HCP 12 months after starting the program. Twelve
      months after initiating the program, a significant knowledge improvement was
      noted in all groups of HCP except medical doctors. Nurses presented the most
      significant rise in knowledge score (P < .001). In conclusion, the consultation
      is an acceptable and effective form of long-term educational program for HCP in a
      hospital setting with a huge majority of patients suffering from chronic vascular
      and neurological conditions and loss of protective pain sensation at the lower
      limb.

PMID- 17558005
TI  - Effects of Hibiscus rosa sinensis L (Malvaceae) on wound healing activity: a
      preclinical study in a Sprague Dawley rat.
AB  - Hibiscus rosa sinensis (H rosa sinensis), a plant product, has been used for the
      treatment of a variety of diseases as well as to promote wound healing. The wound
      healing activity of the ethanol extract of H rosa sinensis flower was determined
      in rats, using excision, incision, and dead space wound models and is presented
      in this report. The animals were randomly divided into 2 groups of 6 each in all
      the models. Test group animals in each model were treated with the ethanol
      extract of H rosa sinensis orally by mixing in drinking water (120 mg kg(-1) day(
      1)), and the control group animals were maintained with plain drinking water.
      Healing was assessed by the rate of wound contraction, period of
      epithelialization, tensile strength (skin breaking strength), granulation tissue
      weight, and hydroxyproline content. The antimicrobial activity of the flower
      extract against selected microorganisms that infect the wounds was also assessed.
      Animals treated with the extract exhibited an 86% reduction in the wound area
      compared with controls, who exhibited a 75% reduction. The extract-treated
      animals were found to epithelize their wounds significantly faster than controls
      (P < .002) and have shown significantly higher skin-breaking strength than
      controls (P < .002). The dry and wet weight of granulation tissue and
      hydroxyproline content were also increased significantly when compared with
      controls. The reported observations suggest H rosa sinensis aids wound healing in
      the rat model.

PMID- 17558006
TI  - The extracellular matrix in wound healing: a closer look at therapeutics for
      chronic wounds.
AB  - Disappointing results with the use of exogenous recombinant growth factors in
      chronic wounds have redirected the focus to the extracellular matrix (ECM). Newer
      research has clearly changed our view on the role of the ECM in tissue repair and
      dismissed the dogma that the sole function of ECM is a passive physical support
      for cells. It is now clear that intact or fragmented ECM molecules are capable of
      transducing signals pivotal for cell processes in wound healing primarily via
      integrin interactions in concert with growth factor activation. In addition, our
      knowledge about ECM molecules in minute concentrations with biological activity,
      but devoid of significant structural influence, is increasing. This article
      reviews the multifaceted molecular roles of ECM in the normal wound-healing
      process and some molecular abnormalities in chronic wounds, and touches on
      potential therapies based on the developments of tissue biology.

PMID- 17558007
TI  - Civilian gas gangrene: a clinical challenge.
AB  - Gas gangrene due to clostridia infections is commonly seen in war injuries and is
      much less commonly seen in civilian life. When such problems do occur, they
      present a challenge to the surgeon due to the associated high morbidity and
      mortality associated. A case is presented where a patient developed gas gangrene
      in a limb consequent to trauma that had been treated surgically. It is vital to
      make a correct diagnosis at the earliest to limit disease progression and to
      avoid complications.

PMID- 17558008
TI  - Arthrodesis with external fixation in the unstable or misaligned Charcot ankle in
      patients with diabetes mellitus.
AB  - The unstable or misaligned Charcot ankle with or without chronic foot ulceration
      is a major clinical challenge. When it cannot be accommodated with an ankle foot
      orthosis, surgical treatment is indicated in order to avoid leg amputation. This
      requires extensive soft tissue release and bony resection to realign the foot and
      arthrodesis with internal or external fixation. The guidance in the literature
      favors internal fixation. This article reports results with external fixation in
      11 patients (12 feet) over a period of 12 years. External fixation was chosen as
      the surgical option because of the presence of foot ulcers with the attendent
      risk of infection. There were 7 tibio-talar and 5 tibio-calcaneal fusions.
      Compression was applied for 6 weeks with an external frame according to Charnley,
      followed by 6 weeks with total-contact cast. Weight bearing with a rigid leather
      brace was allowed after 12 weeks. In one case, transtibial amputation was
      required due to loosening of the distal pins from osteopenic disintegrating bone.
      In 11 cases (92%), the foot was successfully realigned and independent walking
      with a brace retained during the follow-up of median 48 months (10-102 months).
      Bony union took place in 5 out of 7 cases with tibio-talar fusion and in 1 out of
      5 with tibio-calcaneal fusion. The functional result in cases with fibrous union
      was, however, satisfactory. Although meaningful comparisons of series are
      difficult to conduct and interpret from, the limb salvage rate was similar to
      results with internal fixation. The authors consider the results to be
      encouraging and to be used to develop a higher level of evidence.

PMID- 17558010
TI  - Utilizing a crossover reverse sural artery flap for soft tissue reconstruction of
      the plantar forefoot after a severe degloving injury.
AB  - Extensive soft tissue defects involving the weight-bearing areas of the plantar
      aspect of the foot often require coverage with flaps. The options often include
      free flaps, free muscle flaps with split-thickness skin grafting, or local flaps.
      When presented with high-energy-induced soft tissue injuries of the foot, choices
      become narrow, secondary to the associated zone of injury. Free flaps require a
      viable recipient vessel suitable for microvascular anastomosis. Split-thickness
      skin grafts applied to the plantar aspect of the foot are prone to persistent
      breakdown. Local flaps if available are useful for coverage of plantar soft
      tissue defects. However, when local flaps of the affected limb are compromised or
      extension is not sufficient for coverage, crossover leg and foot flaps become
      invaluable. The reported cases of crossover sural artery flaps are sparse. To the
      best of the authors' knowledge, the few reported cases of crossover leg and sural
      artery flaps were described to provide soft tissue coverage over the heel and
      leg. The authors report a case of a crossover reverse sural artery flap for soft
      tissue coverage to the plantar aspect of the forefoot after a high-energy-induced
      degloving injury.

PMID- 17558009
TI  - Improvement of idiopathic pyoderma gangrenosum during treatment with anti-tumor
      necrosis factor alfa monoclonal antibody.
AB  - Pyoderma gangrenosum (PG) is an inflammatory ulcerative condition of unknown
      etiology. An autoimmune mechanism including immune complex-mediated neutrophilic
      vascular reactions has been suggested. The role of tumor necrosis factor (TNF) in
      PG remains unclear. Evidence supports the idea that TNF plays a role in chronic
      inflammation and migration of neutrophils to these lesions. PG is frequently
      associated with various diseases, but up to 50% of cases are idiopathic. There
      are several reports describing the successful use of infliximab (Remicade,
      Centocor, Inc, Horsham, Pa), a chimeric antitumor necrosis factor alpha
      monoclonal antibody, in the treatment of inflammatory bowel disease- associated
      PG, but there have been few reported cases of infliximab in the treatment of
      idiopathic PG. The authors present a dramatic improvement in 4 cases of
      idiopathic PG of the lower leg treated with infliximab.

PMID- 17558011
TI  - Surgical robotics for patient safety in the perioperative environment: realizing
      the promise.
AB  - Surgery is at a crossroads of complexity. However, there is a potential path
      toward patient safety. One such course is to leverage computer and robotic assist
      techniques in the reduction and interception of error in the perioperative
      environment. This white paper attempts to facilitate the road toward realizing
      that promise by outlining a research agenda. The paper will briefly review the
      current status of surgical robotics and summarize any conclusions that can be
      reached to date based on existing research. It will then lay out a roadmap for
      future research to determine how surgical robots should be optimally designed and
      integrated into the perioperative workflow and process. Successful movement down
      this path would involve focused efforts and multiagency collaboration to address
      the research priorities outlined, thereby realizing the full potential of
      surgical robotics to augment human capabilities, enhance task performance, extend
      the reach of surgical care, improve health care quality, and ultimately enhance
      patient safety.

PMID- 17558012
TI  - A pervasive body sensor network for measuring postoperative recovery at home.
AB  - Patients going home following major surgery are susceptible to complications such
      as wound infection, abscess formation, malnutrition, poor analgesia, and
      depression, all of which can develop after the fifth postoperative day and slow
      recovery. Although current hospital recovery monitoring systems are effective
      during perioperative and early postoperative periods, they cannot be used when
      the patient is at home. Measuring and quantifying home recovery is currently a
      subjective and labor-intensive process. This case report highlights the
      development and piloting of a wireless body sensor network to monitor
      postoperative recovery at home in patients undergoing abdominal surgery. The
      device consists of wearable sensors (vital signs, motion) combined with
      miniaturized computers wirelessly linked to each other, thus allowing continuous
      monitoring of patients in a pervasive (unobtrusive) manner in any environment.
      Initial pilot work with results in both the simulated (with volunteers) and the
      real home environment (with patients) is presented.

PMID- 17558013
TI  - Outcomes of right- compared with left-side colectomy.
AB  - Right colon resections are perceived as less morbid than left colon resections.
      The purpose of this study was to determine the differences in outcomes between
      right-and left-side colon resections. We reviewed 420 consecutive open
      colectomies over 4 years. Patient demographics, surgical indications,
      intraoperative variables, and outcomes were collected. Two hundred twenty-three
      right colectomies (RCs) were compared with 197 left colectomies (LCs). RCs were
      more often required for cancer (111 vs 65, P < .001) and LCs for diverticular
      disease (10 vs 90, P < .001). LCs were more often performed emergently (36% vs
      23%, P = .004) and required longer mean operative times (149 minutes vs 130
      minutes, P = .004). Complications and mortality in the two groups were equal
      statistically. In the emergent colectomy subset, LCs were associated with greater
      intraoperative blood loss (315 vs 201 mL, P = .02) but fewer complications (11%
      vs 17%, P = .003).

PMID- 17558014
TI  - Minimally invasive management of intrathoracic leaks after esophagogastrectomy.
AB  - Enthusiasm for minimally invasive esophagectomy is increasing. When feasible, the
      laparoscopic and thoracoscopic Ivor Lewis esophagogastrectomy with construction
      of an intrathoracic anastomosis is favored. A potential catastrophic consequence
      of an intrathoracic anastomosis is a postoperative leak. In this review, the
      authors summarize the current understanding of the pathophysiology and the
      management of intrathoracic leak using minimally invasive surgical techniques.

PMID- 17558015
TI  - Individual physician experience with laparoscopic supracervical hysterectomy in a
      single outpatient setting.
AB  - The authors report the surgical experience of a single physician operating at 1
      outpatient surgery center using laparoscopic supracervical hysterectomy for the
      treatment of 100 patients with benign gynecologic disease. Operative status was
      evaluated in terms of patient morbidity, length of surgery, blood loss, and
      duration of hospital stay. The mean operative time was 2.6 hours, and the mean
      anesthesia time was 3.2 hours. The mean estimated blood loss was 116.6 mL, and
      the mean patient hospital stay was 16.5 hours. There were no reported
      intraoperative or postoperative complications. Laparoscopic supracervical
      hysterectomy was not feasible and was converted to laparotomy and total abdominal
      hysterectomy in 4 patients. The authors present one of the first individual
      physician experiences at a single outpatient surgery center using laparoscopic
      supracervical hysterectomy for benign gynecologic conditions. Optimal patient
      postoperative stay and a minimal complication rate suggest that this procedure
      performed at a single outpatient surgery center is feasible.

PMID- 17558016
TI  - Design of a proficiency-based skills training curriculum for the fundamentals of
      laparoscopic surgery.
AB  - Currently, no optimal curriculum exists for the Fundamentals of Laparoscopic
      Surgery (FLS) manual skills training program. The objective was to create a
      proficiency-based training curriculum that would allow both successful completion
      of the FLS manual skills exam and improved performance in the operating room. Two
      experienced laparoscopic surgeons performed 5 consecutive repetitions of all 5
      FLS tasks. The mean performance times for both subjects were determined. Error
      parameters for each task were also recorded and used to establish a maximum
      allowable error parameter for each task. These data were used to create both
      error- and time-based proficiency levels for each task based on the importance of
      the task and the amount of resources consumed when practicing the task. This type
      of objective proficiency level was determined for each of the 5 FLS tasks. We
      have developed a proficiency-based training curriculum for the psychomotor skills
      portion of FLS. Work is under way to evaluate and validate this curricular
      design.

PMID- 17558017
TI  - Assessing technical skill in surgery and endoscopy: a set of metrics and an
      algorithm (C-PASS) to assess skills in surgical and endoscopic procedures.
AB  - Historically, the performance of surgeons has been assessed subjectively by
      senior surgical staff in both training and operating environments. In this work,
      the position and motion of surgical instruments are analyzed through an objective
      process, denoted C-PASS, to measure surgeon performance of laparoscopic,
      endoscopic, and image-guided procedures. To develop C-PASS, clinically relevant
      performance characteristics were identified. Then measurement techniques for
      parameters that represented each characteristic were derived, and analytic
      techniques were implemented to transform these parameters into explicit, robust
      metrics. The metrics comprise the C-PASS performance assessment method, which has
      been validated over the last 3 years in studies of laparoscopy and endoscopy.
      These studies show that C-PASS is straightforward, reproducible, and accurate. It
      is sufficiently powerful to assess the efficiency of these complex processes. It
      is likely that C-PASS and similar approaches will improve skills acquisition and
      learning and also enable the objective comparison of systems and techniques.

PMID- 17558018
TI  - Reliable assessment of laparoscopic performance in the operating room using
      videotape analysis.
AB  - The Global Operative Assessment of Laparoscopic Skills (GOALS) is a valid
      assessment tool for objectively evaluating the technical performance of
      laparoscopic skills in surgery residents. We hypothesized that GOALS would
      reliably differentiate between an experienced (expert) and an inexperienced
      (novice) laparoscopic surgeon (construct validity) based on a blinded videotape
      review of a laparoscopic cholecystectomy procedure. Ten board-certified surgeons
      actively engaged in the practice and teaching of laparoscopy reviewed and
      evaluated the videotaped operative performance of one novice and one expert
      laparoscopic surgeon using GOALS. Each reviewer recorded a score for both the
      expert and the novice videotape reviews in each of the 5 domains in GOALS (depth
      perception, bimanual dexterity, efficiency, tissue handling, and overall
      competence). The scores for the expert and the novice were compared and
      statistically analyzed using single-factor analysis of variance (ANOVA). The
      expert scored significantly higher than the novice did in the domains of depth
      perception (p = .005), bimanual dexterity (p = .001), efficiency (p = .001), and
      overall competence ( p = .001). Interrater reliability for the reviewers of the
      novice tape was Cronbach alpha = .93 and the expert tape was Cronbach alpha =
      .87. There was no difference between the two for tissue handling. The Global
      Operative Assessment of Laparoscopic Skills is a valid, objective assessment tool
      for evaluating technical surgical performance when used to blindly evaluate an
      intraoperative videotape recording of a laparoscopic procedure.

PMID- 17558019
TI  - Improving operating room and perioperative safety: background and specific
      recommendations.
AB  - The 1999 Institute of Medicine report To Err Is Human put a spotlight on death
      from preventable medical errors. Surgically related errors are second only to
      medication errors as the most frequent cause of error-related death. Although
      many hospitals have ongoing programs to improve medication safety, most hospitals
      are not focused in a meaningful way on operating room (OR) safety despite the
      import of the OR to the hospital's finances and despite clearly efficacious
      available technologies. The perioperative environment is a high-risk area with
      high velocity, high complexity, and high stakes. OR errors lead to
      disproportionately more harm than errors elsewhere in the hospital. Actual
      adverse events are relatively rare in any given OR suite, but near misses are
      rather common. It is possible to learn much from evaluating near misses (along
      with adverse events) with root-cause analyses and then instituting changes in
      processes and systems to assist humans from making their inevitable errors. This
      article outlines approaches that when combined can markedly improve safety in the
      OR.

PMID- 17558020
TI  - Part-time surgery.

PMID- 17558021
TI  - Can we afford innovation?

PMID- 17558022
TI  - De novo biosynthesis of the late endosome lipid, bis(monoacylglycero)phosphate.
AB  - Bis(monoacylglycero)phosphate (BMP) is a unique lipid enriched in the late
      endosomes participating in the trafficking of lipids and proteins through this
      organelle. The de novo biosynthesis of BMP has not been clearly demonstrated. We
      investigated whether phosphatidylglycerol (PG) and cardiolipin (CL) could serve
      as precursors of de novo BMP synthesis using two different cellular models: CHO
      cells deficient in phosphatidylglycerophosphate (PGP) synthase, the enzyme
      responsible for the first step of PG synthesis; and human lymphoblasts from
      patients with Barth syndrome (BTHS), characterized by mutations in tafazzin, an
      enzyme implicated in the deacylation-reacylation cycle of CL. The biosynthesis of
      both PG and BMP was reduced significantly in the PGP synthase-deficient CHO
      mutants. Furthermore, overexpression of PGP synthase in the deficient mutants
      induced an increase of BMP biosynthesis. In contrast to CHO mutants, BMP
      biosynthesis and its fatty acid composition were not altered in BTHS
      lymphoblasts. Our results thus suggest that in mammalian cells, PG, but not CL,
      is a precursor of the de novo biosynthesis of BMP. Despite the decrease of de
      novo synthesis, the cellular content of BMP remained unchanged in CHO mutants,
      suggesting that other pathway(s) than de novo biosynthesis are also used for BMP
      synthesis.

PMID- 17558023
TI  - Spermidine/spermine-N1-acetyltransferase 2 is an essential component of the
      ubiquitin ligase complex that regulates hypoxia-inducible factor 1alpha.
AB  - Hypoxia-inducible factor 1 (HIF-1) is a heterodimeric transcription factor that
      functions as a master regulator of oxygen homeostasis. The HIF-1alpha subunit is
      subjected to O(2)-dependent prolyl hydroxylation leading to ubiquitination by the
      von Hippel-Lindau protein (VHL)-Elongin C ubiquitin-ligase complex and
      degradation by the 26 S proteasome. In this study, we demonstrate that
      spermidine/spermine-N(1)-acetyltransferase (SSAT) 2 plays an essential role in
      this process. SSAT2 binds to HIF-1alpha, VHL, and Elongin C and promotes
      ubiquitination of hydroxylated HIF-1alpha by stabilizing the interaction of VHL
      and Elongin C. Multivalent interactions by SSAT2 provide a mechanism to ensure
      efficient complex formation, which is necessary for the extremely rapid
      ubiquitination and degradation of HIF-1alpha that is observed in oxygenated
      cells.

PMID- 17558024
TI  - Oxidative stress modulates complement factor H expression in retinal pigmented
      epithelial cells by acetylation of FOXO3.
AB  - Age-related macular degeneration (AMD), the leading cause of severe vision loss
      in the elderly, is a complex disease that results from genetic modifications that
      increase susceptibility to environmental exposures. Smoking, a major source of
      oxidative stress, increases the incidence and severity of AMD, and antioxidants
      slow progression, suggesting that oxidative stress plays a major role.
      Polymorphisms in the complement factor H (CFH) gene that reduce activity of CFH
      increase the risk of AMD. In this study we demonstrate an interaction between
      these two risk factors, because oxidative stress reduces the ability of an
      inflammatory cytokine, interferon-gamma, to increase CFH expression in retinal
      pigmented epithelial cells. The interferon-gamma-induced increase in CFH is
      mediated by transcriptional activation by STAT1, and its suppression by oxidative
      stress is mediated by acetylation of FOXO3, which enhances FOXO3 binding to the
      CFH promoter, reduces its binding to STAT1, inhibits STAT1 interaction with the
      CFH promoter, and reduces expression of CFH. Expression of SIRT1, a mammalian
      homolog of NAD-dependent protein deacetylase sir2, attenuated FOXO3 recruitment
      to the CFH regulatory region and reversed the H(2)O(2)-induced repression of CFH
      gene expression. These data suggest an important interaction between
      environmental exposure and genetic susceptibility in the pathogenesis of AMD and,
      by elucidating molecular signaling involved in the interaction, provide potential
      targets for therapeutic intervention.

PMID- 17558025
TI  - A novel extrapallial fluid protein controls the morphology of nacre lamellae in
      the pearl oyster, Pinctada fucata.
AB  - Mollusk shell nacre is known for its superior mechanical properties and precisely
      controlled biomineralization process. However, the question of how mollusks
      control the morphology of nacre lamellae remains unresolved. Here, a novel 38-kDa
      extrapallial fluid (EPF) protein, named amorphous calcium carbonate-binding
      protein (ACCBP), may partially answer this question. Although sequence analysis
      indicated ACCBP is a member of the acetylcholine-binding protein family, it is
      actively involved in the shell mineralization process. In vitro, ACCBP can
      inhibit the growth of calcite and induce the formation of amorphous calcium
      carbonate. When ACCBP functions were restrained in vivo, the nacre lamellae grew
      in a screw-dislocation pattern, and low crystallinity CaCO(3) precipitated from
      the EPF. Crystal binding experiments further revealed that ACCBP could recognize
      different CaCO(3) crystal phases and crystal faces. With this capacity, ACCBP
      could modify the morphology of nacre lamellae by inhibiting the growth of
      undesired aragonite crystal faces and meanwhile maintain the stability of CaCO(3)
      supersaturated body fluid by ceasing the nucleation and growth of calcite.
      Furthermore, the crystal growth inhibition capacity of ACCBP was proved to be
      directly related to its acetylcholine-binding site. Our results suggest that a
      "safeguard mechanism" of undesired crystal growth is necessary for shell
      microstructure formation.

PMID- 17558026
TI  - Radiographic signs of renal disease in rabbits.
AB  - The radiological features of 65 rabbits with suspected renal disease are
      reviewed. The radiological features included a generalised increase in bone
      opacity (osteosclerosis), renomegaly, nephroliths, ureteroliths and soft tissue
      mineralisation. One or more of these changes were present on radiographs of 57 of
      the 65 rabbits. Renal disease was suspected because of the clinical signs and the
      presence of kidney stones and/or high blood concentrations of urea and
      creatinine. Significant renal disease was confirmed in 14 cases that were
      examined postmortem. Blood urea and creatinine concentrations were measured in 47
      cases but not all the rabbits had high levels of both. Blood calcium
      concentration was high in 33 of the 38 rabbits in which it was measured. Serum
      phosphate was high in 17 and low in five of 34 rabbits in which it was measured.
      Hyperphosphataemia was associated with generalised osteosclerosis and aortic
      calcification. Rabbits with osteosclerosis were thin, depressed and unwilling to
      move. Thirty-eight of 41 rabbits that were tested were seropositive for
      antibodies to Encephalitozoon cuniculi. Histological lesions suggestive of E
      cuniculi infection were found in all 13 cases that were examined postmortem,
      although the organisms were visible in only one case.

PMID- 17558027
TI  - Magnetic resonance imaging of traumatic intervertebral disc extrusion in dogs.
AB  - This retrospective study evaluated the magnetic resonance (mr) images of
      traumatic disc extrusions in 11 dogs. The findings included a reduction in the
      volume and signal intensity of the nucleus pulposus, focal hyperintensity within
      the overlying spinal cord on T (2)-weighted mr images, and subtle spinal cord
      compression, extraneous material or signal change within the vertebral canal. The
      largest area of hyperintensity in the spinal cord was directly over or close to
      the affected disc space, appeared asymmetrical and in the majority of cases was
      less than one vertebra in length. Parenchymal spinal cord haemorrhage was
      identified in four of the dogs. Vacuum phenomena, evident as a signal void in the
      centre of the disc, were identified in two of the dogs. The mr images were
      distinct from those reported for other causes of spinal cord dysfunction.

PMID- 17558028
TI  - Effect of carazolol on the oestrous behaviour and concentrations of luteinising
      hormone and steroids in lactating cows during the periovulatory period.
AB  - Twelve multiparous, cycling, lactating Holstein-Friesian cows were synchronised
      with prostaglandin F(2alpha) and treated with either 2.5 mg carazolol or saline.
      There were no differences between the peripheral blood concentrations of
      oestradiol or progesterone, but in the cows treated with carazolol the
      periovulatory surge of luteinising hormone was delayed, and oestrous behaviour
      was expressed later than in the control cows.

PMID- 17558029
TI  - Farmers' attitudes to methods for controlling tail biting in pigs.

PMID- 17558030
TI  - Coccidiosis in British alpacas (Vicugna pacos).

PMID- 17558031
TI  - Intracorporeal suture reinforcement during laparoscopic gastropexy in dogs.

PMID- 17558032
TI  - Sublingual administration of buprenorphine for long-term analgesia in the horse.

PMID- 17558033
TI  - Castration of donkey foals.

PMID- 17558034
TI  - Occurrence of a second strain of BVDV-2 in the UK.

PMID- 17558035
TI  - Clostridium perfringens type D enterotoxaemia in neonatal lambs.

PMID- 17558036
TI  - Traumatic reticuloperitonitis in cows.

PMID- 17558037
TI  - Diagnosis of fog fever.

PMID- 17558038
TI  - Laparoscopic ovariohysterectomy in dogs.

PMID- 17558039
TI  - Exotic fungal infection in a horse.

PMID- 17558040
TI  - [Detailed review of epidemiologic studies on adult Attention
      Deficit/Hyperactivity Disorder (ADHD)].
AB  - INTRODUCTION: Attention Deficit/Hyperactivity Disorder (ADHD) is one of the most
      frequently diagnosed psychiatric disorders of childhood. It occurs approximately
      in 3-9% of school age children. Despite the fact that it also occurs in adults,
      ADHD represents a barely known and rarely recognized disorder in practice. The
      objective of this article is to provide a detailed review of epidemiological
      research into ADHD in adults. METHODS: Our research group conducted a systematic
      review of the epidemiologic literature on adult ADHD based on the Medline and
      Psychlit databases and papers that have been published during the past 10 years
      (search was conducted on the following key words: "adult", "adhd", "prevalence"
      "epidemiology". RESULTS: Findings from follow-up studies indicate that the
      persistence of symptoms of ADHD in adulthood is in the range of 4-66%. Of the
      population studies that are presented, one estimated the cumulative incidence
      between 5 and 19 years of age; the lower and upper limits of the estimates were
      7.5% and 16%, respectively. Four population studies were concerned with
      prevalence in the general population; thus, providing the most reliable estimates
      for adult ADHD. These studies indicated that, depending on the diagnostic
      criteria employed, the prevalence of ADHD ranged between 1 and 4.7%. CONCLUSION:
      In view of the above epidemiological data and of the fact that most studies
      dealing with adult ADHD have indicated a close link between the symptoms of ADHD
      and severe difficulties in social adaptation (including the ability to work,
      functional problems related to criminal behaviour, and psychiatric comorbidity),
      research into adult ADHD in Hungary, improvement of its diagnosis and
      recognition, and its adequate treatment is of prime importance from the
      perspective of clinical practice.

PMID- 17558041
TI  - [Monitoring of quality of life--review].
AB  - Over the past few years, the study of the Quality of Life (QOL) has become a
      focus of clinical research, with respect to its importance in the assessment of
      functioning. In many chronic illnesses, a linear relationship cannot be found
      between the alleviation of symptoms and long-term functioning. Therefore, the
      efficacy of therapy cannot be estimated only by symptom scales. In addition,
      monitoring of the Quality of Life can be used to assess subjective satisfaction
      with therapy and to estimate its cost-effectiveness. Quality of Life scales have
      two basic subtypes: general and illness-specific questionnaires, which have been
      produced in huge numbers. In view of the fact that quality of life depends on
      culture, validated versions of these questionnaires have made in many countries.
      The topic has a fairly broad scope; therefore, in the present review, we offer a
      brief survey of the QOL-literature published during the last six years on the
      basis of four important journals which have a high impact factor and deal with
      general topics (American Journal of Psychiatry, Archives of General Psychiatry,
      Journal of Clinical Psychiatry, and British Journal of Psychiatry). In the first
      part we introduce the scales that are used most often, while in the second part
      we present the results of the illness-specific research studies. We hope that our
      review will be a good map to the labyrinth of this topic and will provide help
      for selecting the most suitable scale for everyone.

PMID- 17558042
TI  - [Validity and psychometric properties of a quality of life questionnaire in a
      Hungarian child and adolescent population].
AB  - INTRODUCTION: The study of the quality of life in various strata of society is a
      very important task. No quality of life research has been done on the Hungarian
      child population until now. In the present study, we assessed the life quality in
      a sample of elementary school-aged children by asking both the parents and the
      children themselves. METHODS: Data were collected from 2,620 children and their
      parents (mean age: 10.45 years, sd: 2.2 years) by administering the Invertar
      Lebensqualitat Kindern und Jugendlichen (ILK) questionnaire. Reliability and
      validity data of the questionnaire were examined separately for the child,
      adolescent, and parent versions. RESULTS: Internal consistency was adequate in
      all three versions, Cronbach alpha was above 0.6. Test-retest reliability (ICC)
      ranged between 0.67 and 0.75. Discriminant validity was measured in a non
      depressed sample versus a population showing symptoms of clinical depression s.
      Based on the ILK questionnaire, the two samples were clearly different in their
      quality of life. Satisfaction with school and psychic well-being worsens with
      increasing age in the average paediatric population. Relations with family
      members pose problems in 13-15 year-olds, while peer relations cause difficulty
      to 6-9 year-olds. Most often parents underestimate the troubles of their
      children. CONCLUSIONS: The ILK questionnaire is well suited for both
      comprehensive and detailed examinations of quality of life in Hungarian child
      populations. It shows adequate reliability and validity. Further research is
      needed to identify factors influencing the quality of life of Hungarian
      youngsters and to improve therapeutic options.

PMID- 17558043
TI  - [Orthographic aspects of the Hungarian medical literature].

PMID- 17558044
TI  - Check if your trichologist is a doctor: need for educating the public.

PMID- 17558045
TI  - Vitiligo: compendium of clinico-epidemiological features.
AB  - Vitiligo, an autoimmune disorder characterized by localized and/or generalized
      depigmentation of the skin and/or mucous membranes, is a well-recognized entity.
      The imperatives of its epidemiology both in rural India and in global reckoning
      have been highlighted frequently. Its morphology is striking and is characterized
      by asymptomatic ivory/chalky white macule(s) that may be frequently surrounded by
      a prominent pigmented border, the 'trichrome vitiligo'. However vitiligo may have
      morphological variations in the form of: trichrome, quadri-chrome, penta-chrome,
      blue and inflammatory vitiligo. Its current topographical classification into
      segmental, zosteriform and nonsegmental, areata, vulgaris, acrofacialis and
      mucosal represent its well acclaimed presentations. Its adult and childhood onset
      is well appreciated as also its presentation in males and females. Occasionally,
      it may be possible to identify triggering factors. Vitiligo may be associated
      with cutaneous, ocular and systemic disorders, the details of which are discussed
      in this article.

PMID- 17558046
TI  - Niosomal methotrexate gel in the treatment of localized psoriasis: phase I and
      phase II studies.
AB  - BACKGROUND: Efficacy of topical methotrexate in psoriasis is limited by its
      penetration. AIMS: The study involved the preparation of niosomal methotrexate in
      chitosan gel and to test the same for irritation and sensitization on healthy
      human volunteers followed by assessing the efficacy of the gel through double
      blind placebo-controlled study on psoriasis patients and also comparing its
      efficacy with a marketed methotrexate gel. METHODS: The methotrexate niosomes
      were prepared by lipid layer hydration method. The characterized niosomes were
      incorporated in chitosan gel. The gels were tested on 10 human volunteers to
      check for irritation and skin sensitivity by human repeated insult patch test
      (HRIPT). The formulations were assessed for efficacy by double-blind placebo
      controlled study in 10 psoriasis patients for each formulation. The efficacy was
      calculated by psoriasis area and severity index scoring method. The global score
      was used to assess the progress of the disease. RESULTS: The HRIPT test did not
      produce any significant irritation or sensitization on healthy human volunteers.
      The placebo and marketed gels were compared with niosomal methotrexate gel. At
      Week 12, with niosomal methotrexate gel, there was reduction in total score from
      6.2378+/-1.4857 to 2.0023+/-0.1371. CONCLUSION: These results suggest that
      niosomal methotrexate gel is more efficacious than placebo and marketed
      methotrexate gel.

PMID- 17558047
TI  - Vitiligo: a part of a systemic autoimmune process.
AB  - BACKGROUND: Recent clinical and animal experimental studies postulate that the
      pathogenetic mechanisms of vitiligo could be of systemic origin as vitiligo is
      associated with ocular and auditory abnormalities as well as other autoimmune
      disorders.Hence, we studied genetic factors, systemic associations, ocular and
      auditory abnormalities of vitiligo. METHODS: The study group included 150 new
      cases of various types of vitiligo. One hundred age- and sex-matched nonvitiligo
      cases were included as controls in the study. A complete family history was taken
      for all patients. Examination was carried out taking note of the type of vitiligo
      and approximate percentage of body surface involved. All relevant laboratory
      investigations, a thorough audiological examination including pure tone
      audiometry and a complete ophthalmologic examination were carried out in all
      patients and controls. Statistical analysis was done using the Chi square test.
      RESULTS: Fifty-four vitiligo patients (36%) had a family history of vitiligo.
      Anemia was present in 30 (20%) vitiligo patients but only in five (5%) controls,
      a difference that was statistically significant (c2 = 15.8, P < 0.001). Diabetes
      mellitus was present in 24 (16%) vitiligo patients and only 2 (2%) of controls
      (Chi square, c2 = 12.4, P < 0.001). Hypothyroidism and alopecia areata were
      present in 18 (12%) and 11 (7.4%) vitiligo patients respectively and none of the
      controls. Hypoacusis was seen in 30 (20%) vitiligo patients and two (2%) controls
      (c2 = 8.19, P < 0.005). Twenty-four vitiligo patients (16%) and five controls
      (5%) had specific ocular abnormalities like uveitis, iris and retinal pigmentary
      abnormalities (c2 = 7.39, P < 0.001). CONCLUSION: This study demonstrates
      statistically significant clinical evidence confirming that vitiligo is a part of
      systemic autoimmune process.

PMID- 17558048
TI  - A clinical study of psoriatic arthropathy.
AB  - BACKGROUND: The incidence of uncomplicated psoriasis is 1-3% in the general
      population. Arthritis is found in increased frequency in psoriatic patients and
      its incidence is estimated to be 5-7%. AIM: To assess the prevalence of arthritis
      in psoriatic patients. METHODS: Four hundred and seventy-two psoriatic patients
      were enrolled in the study out of which 40 patients had (psoriatic) arthropathy
      (PsA). Severity of psoriasis was assessed by the psoriasis area and severity
      index (PASI). Routine blood investigations were carried out along with
      radiological investigations. RESULTS: Forty percent of the 40 PsA patients were
      in the age group of 51-60 years. Seven patients out of the 40 (17.5%) psoriatic
      arthropathic (PsA) patients had a family history of psoriasis. Nail involvement
      was observed in 37 cases (92.5%). Rheumatoid factor was present in five out of
      the 40 (12.5%) PsA patients. Serum uric acid levels were above normal in eighteen
      out of the 40 (45%) PsA patients. Asymmetric oligoarthropathy was the most
      commonly observed feature in 42.5% of the 40 PsA patients. Narrowing of joint
      spaces and erosions were observed in 62.5% and 45% of the 40 PsA patients.
      CONCLUSION: There is an association between the duration of skin lesions and
      duration of arthropathy. Similarly the PASI score is also directly related with
      arthropathy.

PMID- 17558049
TI  - A mixed longitudinal study of physical growth in children with atopic dermatitis.
AB  - BACKGROUND: Atopic dermatitis is a chronic, relapsing disorder associated with
      significant morbidity. Growth retardation is known to occur in children affected
      with atopic dermatitis. However, there is not enough Indian data for this
      disorder. AIMS: We conducted a longitudinal study to look for the effect of
      atopic dermatitis on growth attainment of Indian preschool children. METHODS: The
      growth patterns of 62 children, aged 3-5 years and suffering from atopic
      dermatitis were studied in terms of body weight, height and head circumference.
      Sixty-eight normal healthy children matched for age, sex and socioeconomic status
      were taken as controls. Every child was followed up at intervals of three months
      following a mixed longitudinal study design for the duration of one year.
      Severity of the disease was determined by the scoring atopic dermatitis (SCORAD)
      index. RESULTS: Growth velocities were lower in patients than in controls. Mean
      changes in body weight of patients of both sexes showed close similarity to
      controls. Mean values for height and head circumference were found to be
      significantly lower in girls than in the girls of the control group at majority
      of the age levels. In contrast, in boys, these values for the patients remained
      comparable or higher than in the boys of the control group at some of the ages.
      Girls had comparatively more severe disease than boys and they had lower values
      than boys for all the growth parameters assessed. CONCLUSION: Growth retardation
      was observed among children with a more severe form of the disease. Height of the
      affected children was compromised mostly, though a tendency for catch-up growth
      was observed. Severe forms of atopic dermatitis may impair a child's linear
      growth temporarily.

PMID- 17558051
TI  - Cutaneous rhinosporidiosis.
AB  - Rhinosporidiosis is a chronic granulomatous disease of the mucocutaneous tissue,
      which clinically presents as polypoidal growths. Cutaneous lesions are infrequent
      and are generally associated with mucosal lesions. We present a case of cutaneous
      rhinosporidiosis in association with recurrent nasopharyngeal rhinosporidiosis in
      a 65-year-old male patient. He presented with dysphagia for solid foods and skin
      growth on the left side of jaw of 2 years duration. Histopathology of cutaneous
      and nasopharyngeal lesions revealed numerous thick walled sporangia in a vascular
      connective tissue along with a granulomatous inflammation confirming the
      diagnosis of cutaneous and nasopharyngeal rhinosporidiosis. Endoscopic removal of
      nasopharyngeal polyp was done and he was started on dapsone therapy.

PMID- 17558050
TI  - Chromoblastomycosis in Nepal: a study of 13 cases.
AB  - BACKGROUND: Chromoblastomycosis is a chronic fungal infection caused by several
      pigmented fungi commonly seen in tropical and subtropical climates. AIM: To
      evaluate the epidemiologic, clinical and pathological characteristics of
      chromoblastomycosis in our patients. METHODS: This retrospective and prospective
      study was conducted at the Manipal Teaching Hospital, Pokhara, Nepal. Clinical
      features and histopathology of all the cases diagnosed as chromoblastomycosis
      during the last eight years were studied. RESULTS: A total of 13 cases of
      chromoblastomycosis were diagnosed during the period of 1999-2006. The disease
      was seen predominantly in middle-aged male farmers and those from rural areas.
      The lesions commonly involved the lower extremity and were single or multiple in
      number. They clinically presented as verrucous or nodular growths. Out of these
      13 cases, three were diagnosed clinically as squamous cell carcinoma and one as
      psoriasis. The histopathological features included sclerotic bodies in 12 cases
      (92%), microabscess formation in 10 cases (76.9%), pseudoepitheliomatous
      hyperplasia in nine cases (69.2%) and granuloma in eight cases (61.5%).
      CONCLUSION: Farming is the commonest occupation in patients with
      chromoblastomycosis. Early histological diagnosis helps in effective management
      of the condition.

PMID- 17558052
TI  - Mucocutaneous nasal histoplasmosis in an immunocompetent young adult.
AB  - A case of mucocutaneous nasal histoplasmosis in an immunocompetent host is
      described below. A 30-year-old male had a broadened nose with swelling and
      repeated blockage of nasal passages for the past six months. Diagnosis was made
      on the basis of histological demonstration of characteristic yeast cells of
      Histoplasma capsulatum var. capsulatum occurring within histiocytes and
      extracellularly in stained smears of fine needle aspirates and biopsy from the
      lesions in ala of the nose and perioral region. The patient showed appreciable
      regression of lesions after three weeks of itraconazole therapy but was not
      available for re-assessment.

PMID- 17558053
TI  - Disseminated cutaneous rhinosporidiosis.
AB  - A 48-year-old male patient presented to Skin and VD outpatient with multiple
      granulomatous growths of different sizes all over the body, including numerous
      subcutaneous swellings mimicking lipomas of 2 years duration. Two and half years
      back he was operated for a polypoidal growth of left nostril with subsequent
      recurrence. Fine needle aspiration cytology and histopathology of the cutaneous
      lesion confirmed the diagnosis as rhinosporidiosis. We report this rare case of
      disseminated cutaneous rhinosporidiosis.

PMID- 17558054
TI  - Cutaneous sporotrichosis of face: polymorphism and reactivation after
      intralesional triamcinolone.
AB  - Cutaneous sporotrichosis, a subcutaneous mycotic infection is caused by the
      saprophytic, dimorphic fungus Sporothrix schenckii. It commonly presents as
      lymphocutaneous or fixed cutaneous lesions involving the upper extremities with
      facial lesions being seen more often in children. The lesions are polymorphic.
      The therapeutic response to saturated solution of potassium iodide is almost
      diagnostic. We describe a culture-proven case of cutaneous sporotrichosis of the
      face mimicking lupus vulgaris initially and basal cell carcinoma later, who did
      not tolerate potassium iodide and failed to respond to treatment with
      fluconazole. The patient had reactivation of infection following an infiltration
      of the scar with triamcinolone acetonide injection. Various other aspects of
      these unusual phenomena are also discussed.

PMID- 17558055
TI  - Pseudoxanthoma elasticum with cerebrovascular accident.
AB  - A 65-year-old male presented with right hemiparesis and skin lesions. On
      examination, the patient had multiple, discrete, skin-colored papules on the neck
      and upper chest with wrinkling of the skin. The lateral part of the trunk and
      medial aspect of both upper arms showed atrophic plaques. A computerized
      tomography scan of the head showed dilatation of the basilar artery with a
      frontoparietal infarct. Funduscopic examination showed characteristic angioid
      streaks. Skin biopsy of the papule and atrophic plaques showed epidermal atrophy,
      calcium deposits in the mid-dermis and basophilic clumped and fragmented elastic
      fibers in the mid- and lower dermis, all findings consistent with pseudoxanthoma
      elasticum. We are reporting here a case of pseudoxanthoma elasticum with
      cerebrovascular accident.

PMID- 17558056
TI  - Multiple dermatofibromas on face treated with carbon dioxide laser.

PMID- 17558057
TI  - Clinical spectrum of dermatoses caused by cosmetics in south India: high
      prevalence of kumkum dermatitis.

PMID- 17558058
TI  - Oculosporidiosis presenting as an under-eye swelling.

PMID- 17558059
TI  - Pilomatricoma in a case of familial xeroderma pigmentosum.

PMID- 17558060
TI  - Umbilical metastasis: an unusual presentation of pancreatic adenocarcinoma.

PMID- 17558061
TI  - Pityriasis rosea occurring during acyclovir therapy.

PMID- 17558062
TI  - Methods of specimen collection for diagnosis of superficial and subcutaneous
      fungal infections.

PMID- 17558063
TI  - Polarized light microscopy.

PMID- 17558064
TI  - Indurated swelling on the thigh.

PMID- 17558065
TI  - Is there a role for glutamine in critical illness?

PMID- 17558066
TI  - Effect of liver disease on maternal and fetal outcome--a prospective study.
AB  - BACKGROUND: Liver disease in pregnancy can have serious consequences. Its
      prevalence, profile and effect on outcome of pregnancy have not been documented
      systematically in India. We prospectively determined the frequency, causes and
      outcome of liver disease in pregnant women. SETTING: Tertiary-care teaching
      hospital. METHODS: Consecutive pregnant women with liver disease attending the
      inpatient or outpatient services of the Departments of Gastro-enterology and
      Obstetrics and Gynecology between December 2002 and October 2004 were evaluated
      and followed up till 2 weeks postpartum or death. RESULTS: Liver disease was
      found in 107 (0.9%) of 12,061 pregnancies. Of these, fifty six (52.3%) had
      pregnancy-specific liver disorders (pregnancy-induced hypertension [PIH]
      associated liver dysfunction 36--including HELLP syndrome 22 and pre-eclamptic
      liver dysfunction 14; intrahepatic cholestasis of pregnancy 10; hyperemesis
      gravidarum 7; acute fatty liver of pregnancy 3). Liver disorders not specific to
      pregnancy included hepatitis E (16), hepatitis B, non A-E hepatitis and chronic
      liver disease (5 each) and others (14); in 6 patients no cause could be found.
      Ninety-six patients completed follow up. Overall maternal and perinatal mortality
      rates were 19.7% and 35.4%, respectively. CONCLUSIONS: PIH-associated liver
      dysfunction was the most common cause of liver disease in pregnancy. This is
      associated with significant maternal and perinatal morbidity and mortality.

PMID- 17558067
TI  - Laparoscopic management of duodenal ulcer perforation: is it advantageous?
AB  - BACKGROUND: Surgery is the mainstay of treatment of patients with peptic duodenal
      perforation. With the advent of minimal access techniques, laparoscopy is being
      used for the treatment of this condition. METHODS: Retrospective analysis of 120
      consecutive patients (mean age 44.5 years; 111 men) with duodenal ulcer
      perforation who had undergone laparoscopic surgery. RESULTS: 87 patients had
      history of tobacco consumption, 12 were chronic NSAID users, 72 had Helicobacter
      pylori infection and 36 had a co-morbid condition. The mean time to surgery from
      onset of symptoms was 28.4 hours. The median operating time was 46 minutes. All
      patients underwent laparoscopic closure of the perforation with Graham's patch
      omentopexy; 12 patients underwent additional definitive ulcer surgery. The
      morbidity rate was 7.5%; no patient needed conversion to open surgery or died.
      The mean postoperative hospital stay was 5.8 days. CONCLUSION: Results of
      laparoscopic management of perforated peptic ulcer are encouraging, with no
      conversion to open surgery, low morbidity and no mortality.

PMID- 17558068
TI  - Role of magnification endoscopy in the diagnosis and evaluation of suspected
      celiac disease: correlation with histology.
AB  - BACKGROUND: Magnification endoscopy (ME), with 115-fold magnification, allows
      visualization of duodenal villi. We assessed the efficacy of ME for evaluation of
      villous atrophy. METHODS: ME and duodenal biopsy were done in 16 patients with
      suspected celiac disease and 16 control subjects undergoing endoscopy for reflux
      symptoms. The pathologist was unaware of the ME findings. RESULTS: Sensitivity,
      specificity and positive and negative predictive values for villous atrophy
      (partial or total) were 100%, 91%, 83% and 100%, respectively. Corresponding
      values for normal villous structure were 91%, 100%, 100% and 83%, respectively.
      There was significant concordance between the ME and histology findings.
      CONCLUSION: ME is a reliable technique to diagnose villous atrophy.

PMID- 17558069
TI  - Effect of oral glutamine administration on oxidative stress, morbidity and
      mortality in critically ill surgical patients.
AB  - OBJECTIVE: To examine the effect of enteral administration of glutamine in
      patients with peritonitis or abdominal trauma. METHODS: In a prospective,
      interventional, observer-blind, randomized clinical trial, 120 patients, aged 18
      60 years, were randomized to receive either enteral glutamine 45 g/day for 5 days
      in addition to standard care (n=63; group A) or standard care alone (n=57; group
      B). Surgical intervention was done as needed. RESULTS: The two groups were
      comparable for sex and severity of illness scores. Following treatment, serum
      malondialdehyde (MDA) levels in group A increased from 4.4 (8.0) to 7.2 (4.8)
      mmol/mL, whereas those in group B decreased from 3.9 (4.9) to 3.1 (5.0) mmol/mL;
      these changes were not statistically significant. Reduced glutathione levels
      increased from 0.03 (0.04) to 0.06 (0.12) mg/g Hb (p=0.032) after treatment in
      group A and from 0.03 (0.03) to 0.05 (0.04) mg/g Hb (p=0.001) in group B.
      Infectious complications were equally frequent in the two groups (group A: 44;
      group B: 37; p=0.571). Survival rate and duration of hospital stay were also
      comparable in the two groups. CONCLUSION: Enteral glutamine supplementation
      offers no advantage in patients with peritonitis or abdominal trauma.

PMID- 17558070
TI  - Evaluation of relationship between clinical and colonoscopic features in patients
      with active ulcerative colitis.
AB  - OBJECTIVE: To develop a system to score disease activity based on clinical
      manifestations in patients with active ulcerative colitis and to assess the
      relationship of this score with endoscopic disease severity as assessed by
      colonoscopy. METHODS: In a pilot study of 43 patients, nine clinical variables
      were examined by univariate analysis. Six factors that correlated with disease
      severity included age, well-being, defecation frequency, bloody stool,
      extraintestinal manifestations (Ext) and hemoglobin (Hb). Multivariate analysis
      resulted in the generation of a new activity index for the prediction of disease
      severity. Validation of this index was performed on 88 patients with definite
      diagnosis of ulcerative coli-tis based on previous histological examination.
      RESULTS: The activity index is derived as follows: (18 x bloody stool) + (20 x
      defecation frequency) + (5 x Ext) + (15 x Hb) - (well-being x 17) + (age x 2) +
      158. Values below 280, between 280 and 310 and above 310 corresponded to mild,
      moderate and severe disease, respectively. The model classified disease severity
      correctly in 71% of cases. CONCLUSION: This activity index may be useful for
      noninvasive evaluation of disease severity in patients with ulcerative colitis.

PMID- 17558071
TI  - Changing profile of Budd Chiari syndrome in India.
AB  - There is increasing evidence that Budd Chiari syndrome occurs when acquired
      predisposing factor(s) affect a susceptible individual with one or more
      underlying thrombophilic conditions. Geographical variations in disease pattern
      of Budd Chiari syndrome exist, which may reflect differing predisposing factors.
      We review a change in disease profile of Budd Chiari syndrome in India over the
      past three decades. While earlier studies from India reported isolated inferior
      vena cava (IVC) obstruction as the commonest disease type, this is a minority in
      more recent reports where a combination of IVC and hepatic vein obstruction is
      the commonest type. Longer duration of illness has been shown to be associated
      with IVC obstruction and the recent change in disease profile in India may
      reflect earlier diagnosis of Budd Chiari syndrome. Poverty, malnutrition,
      recurrent bacterial infections and filariasis have been previously suggested as
      predisposing factors for IVC obstruction. Improvement in hygiene and sanitation
      may partly explain the recent change in disease profile of Budd Chiari syndrome
      in India.

PMID- 17558072
TI  - Fever, jaundice, altered sensorium, with multiple systemic manifestations.

PMID- 17558073
TI  - Congenital intrahepatic porto-systemic venous shunt with galactosemia.
AB  - We report a 51-day-old infant with congenital intrahepatic porto-systemic venous
      shunt associated with galactosemia, who presented with cholestatic jaundice. He
      was treated with ursodeoxycholic acid, calcium supplements and galactose-free
      diet. The child was asymptomatic six weeks later.

PMID- 17558075
TI  - Wegener's granulomatosis--an etiology of acute pancreatitis.
AB  - Wegener's granulomatosis is a systemic disease that usually involves the upper
      respiratory tract and kidneys. We report a 47-year-old man with Wegener's
      granulomatosis that presented as acute pancreatitis.

PMID- 17558074
TI  - Reversal of severe hepato-pulmonary syndrome in congenital hepatic fibrosis after
      living-related liver transplantation.
AB  - We report a 5-year-old girl with congenital hepatic fibrosis who presented with
      clubbing and cyanosis. Partial pressure of oxygen was 40 mmHg with oxy-gen
      saturation of 70% on room air, which improved to 128 mmHg and 92% on inhalation
      of 100% oxygen. Macroaggregated albumin scan showed 58% shunting to the brain,
      suggestive of severe hepatopulmonary syndrome. Echocardiogram and pulmonary
      angiogram ruled out pulmonary hypertension. Four weeks after living-related liver
      transplantation, she had normal blood gases and reduction in shunting to 7% on
      macroaggregated albumin scan.

PMID- 17558076
TI  - Hepatic calcification following dengue virus-induced fulminant hepatic failure.
AB  - Hepatic calcification can be seen with various infectious and neoplastic
      conditions. We report a 32-year- old man who developed massive calcification in
      the right lobe of liver following recovery from dengue virus-associated fulminant
      liver failure.

PMID- 17558077
TI  - Non-resolving liver abscess with Echinococcus cross-reactivity in a non-endemic
      region.
AB  - A 40-year-old woman presented with high fever with chills and rigors. Imaging
      studies revealed multiple liver abscesses with hepatosplenomegaly and gall
      stones. Ultrasound-guided aspirate revealed pus that was negative on Gram and
      acid-fast staining and for amebic trophozoites. ELISA for echinococcus was
      strongly positive, but she did not respond to albendazole therapy. At surgery,
      Fasciola hepatica was detected and she responded well to bithinol postoperative.

PMID- 17558078
TI  - Pancreatic epidermoid cyst.
AB  - Epidermoid cyst of intrapancreatic spleen is described but epidermoid cyst
      occurring in the pancreas itself is not documented. We report a 36-year-old man
      who presented with abdominal pain radiating to the back. On ultrasonography, a
      multilocular cyst was seen in the head of the pancreas. Fine-needle aspiration
      cytology suggested a diagnosis of epidermoid cyst, which was confirmed on
      histology of the resected specimen.

PMID- 17558079
TI  - Portal hypertension associated with sickle cell disease.
AB  - We report a 12-year-old girl with sickle cell disease who presented with pain in
      abdomen, fever, joint pain and hematemesis. On examination she had mild jaundice
      and splenomegaly. Upper GI endoscopy showed esophageal varices. She was treated
      with variceal band ligation and is well on folic acid supplements and
      propranolol.

PMID- 17558080
TI  - Folic acid protects hepatobiliary function in ischemic reperfusion injury of rat
      liver.

PMID- 17558081
TI  - Efficacy and safety of Rigiflex pneumatic dilation of achalasia under direct
      endoscopy.

PMID- 17558083
TI  - Feasibility of reusing negative rapid urease test (CLOtest) kit.

PMID- 17558082
TI  - Glutathione-S-transferase M1, T1 and P1 gene polymorphisms in type I autoimmune
      hepatitis: a case-control study.

PMID- 17558084
TI  - Comparative study of proton pump inhibitors for triple therapy in H. pylori
      eradication.

PMID- 17558085
TI  - Use of spiral CT to demonstrate esophageal lumen in corrosive strictures.

PMID- 17558086
TI  - Acute viral hepatitis E and Japanese encephalitis: an unusual co-occurrence.

PMID- 17558087
TI  - Repeated gastrointestinal malignancies in a victim of sulfur mustard gas attack.

PMID- 17558088
TI  - Acute pancreatitis and its association with hyperhomocysteinemia.

PMID- 17558089
TI  - Spontaneous remission of autoimmune hepatitis in pregnancy and postpartum flare.

PMID- 17558090
TI  - Areca nut use in India.

PMID- 17558091
TI  - Areca nut: the hidden Indian 'gateway' to future tobacco use and oral cancers
      among youth.

PMID- 17558092
TI  - Perspectives on the adoption of emergency contraceptive pills as a new
      contraceptive method.

PMID- 17558093
TI  - Hormonal emergency contraception: increasing awareness and access.

PMID- 17558094
TI  - Healing and preventing the diabetic foot wound: where technology, economics and
      common sense converge.

PMID- 17558095
TI  - Altered oxidant-antioxidant status in non-obese men with moderate essential
      hypertension.
AB  - BACKGROUND: Although a wide number of experimental evidences are available
      regarding oxidant-antioxidant disturbance in hypertension, clinical data
      supporting it is lacking in men in early stages of hypertension. AIMS: The
      objective of the study was to evaluate oxidative status and antioxidant
      activities in males with stage I essential hypertension. MATERIALS AND METHODS:
      Thirty hypertensives and 21 normotensives were included in the study. Protein
      carbonyl, reduced glutathione, glutathione peroxidase, catalase and fasting
      glucose were assessed in both the groups. STATISTICAL ANALYSIS: Results were
      analyzed by student's 't' test and linear regression analysis test. RESULTS:
      Plasma protein carbonyl and glutathione peroxidase were significantly increased
      and catalase and GSH were significantly reduced in the hypertensive group
      compared to normotensive subjects. There was a significant negative correlation
      between glutathione peroxidase and catalase in the test group. CONCLUSIONS: The
      data from the present study indicates an alteration in oxidant-antioxidant status
      in non-obese men in early stages of essential hypertension.

PMID- 17558096
TI  - Areca nut use in rural Tamil Nadu: a growing threat.
AB  - BACKGROUND: Areca nut is the fourth main psychoactive substance in the world. In
      India, tobacco is added to the quid and the commercially manufactured
      nonperishable forms of betel quid (pan masala or gutkha) are on the rise in the
      market. OBJECTIVE: To find out the prevalence of areca nut among the rural
      residents of Sriperambudur Taluk. SETTINGS AND DESIGN: A community-based survey
      using pre-tested semi-structured questionnaire. MATERIALS AND METHODS: The survey
      was conducted in 2 villages and their colonies, which were randomly selected out
      of 168 villages. Data was collected from 500 residents of the study population.
      The survey was conducted for a period of 2 months. STATISTICAL ANALYSIS: SPSS
      version 10.0. RESULTS: The study participants were more likely to initiate areca
      nut use by 22 years of age. As many as 19.8% (n = 99) of the study participants
      chewed areca nut products, out of whom 11.2% (n = 56) indulged in chewing habit
      alone (areca nut products). Areca nut use was higher among male study subjects
      compared to females. The commercial forms of areca nut products (gutkha) were the
      most prevalent ones [47.5% (n = 47) of those who used areca nut] observed in the
      community. Compared to female participants, male participants were more likely to
      perceive areca nut use as the most harmful habit draining the community health
      and wealth. CONCLUSION: There seems to be an increase in the prevalence of areca
      nut use. The community also perceives it to be a harmful habit. Therefore,
      effective interventions should be targeted towards the high-risk subpopulation of
      the community to decrease the prevalence of areca nut use in rural Tamil Nadu.

PMID- 17558097
TI  - Awareness of emergency contraception among female college students in Chandigarh,
      India.
AB  - Adolescents and young women are at the greatest risk of unintended pregnancy
      because they are unlikely to see a family planning provider before or immediately
      after the sexual activity. Therefore, preventing unintended pregnancy among them
      is the important concern. Sexually active young women are clients with special
      needs for contraception. They are eligible to use a variety of the available
      contraceptives. Introduction of emergency contraception (EC) in the recent past
      can help them avoid such unintended pregnancies. OBJECTIVE: To investigate the
      awareness of emergency contraception in female college students. STUDY DESIGN:
      Cross-sectional, questionnaire-based study. MATERIALS AND METHODS: This study was
      conducted among college-going undergraduate and graduate female students of
      Punjab University, Chandigarh. Systematic random sampling was used to select the
      respondents. RESULTS: Of the 1,017 college students included in the study, 507
      (49.9%) knew about different contraceptive methods. Maximum awareness was
      regarding oral contraceptive pills (239, 47.1%). Only 74 (7.3%) had knowledge
      about emergency contraceptive pills (ECP). Of them, 10 (14.7%) students knew the
      correct time for use of ECP and the side effects of ECP were known to 48 (88.9%)
      respondents. CONCLUSIONS: Awareness about ECP was very low among female college
      students of Chandigarh, especially regarding correct timing of its use and its
      side effects. Appropriate awareness programs on EC are needed for them.

PMID- 17558099
TI  - Bisalbuminemia in an adult male with Alzheimer's disease.

PMID- 17558098
TI  - Immunomodulatory role of Tinospora cordifolia as an adjuvant in surgical
      treatment of diabetic foot ulcers: a prospective randomized controlled study.
AB  - BACKGROUND: Chronic diabetic patients with wounds have deficient growth factors
      and impaired local and systemic cellular immunity. Treatment with growth factors
      is expensive with risk of infection transmission and these factors may not
      achieve optimum wound concentration. We evaluated the role of generalized
      immunomodulation in diabetic ulcers by using Tinospora cordifolia as an adjuvant
      therapy and studied its influence on parameters/determinants of healing, on
      bacterial eradication and on polymorphonuclear phagocytosis. MATERIALS AND
      METHODS: A prospective double-blind randomized controlled study lasting for over
      18 months in 50 patients. The ulcer was classified by wound morphology and
      severity with Wound Severity Score (Pecoraro-Reiber system). Mean ulcer area,
      depth and perimeter were measured and swabs taken for culture. Blood was
      collected to assess polymorphonuclear % phagocytosis (PMN function by Lehrer
      Cline C. albicans method). Medical therapy, glycemic control, debridement, wound
      care were optimized. At 4 weeks, parameters were reassessed. PMN function was
      reviewed at 3 months. RESULTS AND ANALYSIS: Forty-five patients completed the
      trial: study group - 23 (M:F = 17:1; mean age = 56.3 years; mean ulcer duration =
      21.1 days); control group 22 (M:F = 19:3; mean age = 56.3 years; mean ulcer
      duration = 30.4 days). Net improvement was seen in 17 patients (73.9%) in the
      study group; while in the control group, in 13 patients (59.1%); P = 0.292.
      Specific parameters included rate of change of ulcer area - cm(2) /day (study -
      0.15; control - 0.07; P = 0.145); rate of change of ulcer perimeter - mm/day
      (study - 0.09; control = - 0.07; P = 0.089); change of depth - mm (study - 2.2;
      control - 1.4; P = 0.096); change of wound score (study - 14.4; control - 10.6; P
      = 0.149); total number of debridements (study - 1.9; control - 2.5; P = 0.03) and
      change in % phagocytosis (study - 3.9; control - 2.3; P = 0.048). CONCLUSION:
      Diabetic patients with foot ulcers on T. cordifolia as an adjuvant therapy showed
      significantly better final outcome with improvement in wound healing. Reduced
      debridements and improved phagocytosis were statistically significant, indicating
      beneficial effects of immunomodulation for ulcer healing.

PMID- 17558100
TI  - Myasthenia gravis and autonomously functioning thyroid nodule--a rare
      association.

PMID- 17558101
TI  - Poststerilization regret: findings from India and the United States.

PMID- 17558102
TI  - Prevalence of, and awareness about, sexually transmitted infections among males
      in Delhi.

PMID- 17558103
TI  - Homocysteine in cardiovascular disease: a culprit or an innocent bystander?
AB  - Whether hyperhomocysteinemia is a cardiovascular risk factor or is just an
      epiphenomenon is a subject of debate. More than 20 prospective and 30
      retrospective studies on the topic have been published. Despite huge literature
      available, an unequivocal view has not been firmly established. Medical
      fraternity is still witnessing differing opinions regarding need to treat
      hyperhomocysteinemia. A medical practitioner needs to be well informed of
      developments and current opinion on this subject as it has a strong bearing on a
      major emerging public health problem of cardiovascular disease (CVD). This review
      presents the two views - for and against the acceptance of association between
      hyperhomocysteinemia and cardiovascular disease - and their basis. The two views
      are examined in the light of clinical, epidemiologic and genetic studies, reviews
      and meta-analyses available. Following conclusion was drawn from the exercise:
      The available evidence indicates that homocysteine is not an innocent bystander;
      it is an independent risk factor for CVD. The need for homocysteine-lowering
      therapy is however not yet unequivocally established. Physicians need to be
      vigilant of the updates on this much-debated topic thrusted on them time and
      again.

PMID- 17558104
TI  - The so-called intervertebral disc: a 4-D reverie.

PMID- 17558105
TI  - Invited commentary. Mini mental status examination and the Addenbrooke's
      cognitive examination: effect of education and norms for a multicultural
      population.

PMID- 17558106
TI  - Invited commentary. Sarcoglycanopathies: a clinico-pathological study.

PMID- 17558107
TI  - Invited commentary. Stroke preventive treatment using perindopril and indapamide
      in the context of Indian primary care.

PMID- 17558109
TI  - Invited commentary. From clinical trial to clinical practice.

PMID- 17558110
TI  - Invited commentary. Electrodiagnostic studies in ulnar neuropathy at the elbow.

PMID- 17558111
TI  - Invited commentary. Ulnar motor conduction studies with FDI CMAP recording for
      the electrodiagnosis of ulnar neuropathy at elbow.

PMID- 17558112
TI  - Mini mental state examination and the Addenbrooke's cognitive examination: effect
      of education and norms for a multicultural population.
AB  - OBJECTIVE: To derive population norms on the Malayalam adaptation of
      Addenbrooke's Cognitive Examination (M-ACE) and the inclusive Malayalam mini
      mental state examination (M-MMSE). MATERIALS AND METHODS: Education-stratified
      norms were obtained on randomly selected cognitively unimpaired community elders
      (n = 519). RESULTS: Valid data on norms was available on 488 subjects (age 68.5
      +/- 7.1 and education 7.9 +/- 5.4). Education and age, but not gender had a
      significant effect on both M-ACE and M-MMSE. When compared to the effect of age,
      the effect of education was sevenfold more on the M-ACE and ninefold more on the
      M-MMSE. The mean composite score on the M-ACE (and the M-MMSE) was 42.8 +/- 9.8
      (14.9 +/- 3.1) for those with 0 (n = 72), 55.9 +/- 12.5 (19.7 +/- 4.1) with 1-4
      (n = 96), 62.6 +/- 11.4 (21.9 +/- 3.7) with 5-8 (n = 81), 77 +/- 10.2 (25.7 +/-
      2.4) with 9-12 (n = 136) and 83.4 +/- 7.2 (26.7 +/- 1.6) with > 12 (n = 103)
      years of formal education. CONCLUSIONS: Education has the most potent effect on
      performance on both M-ACE and M-MMSE in the Indian cohort. Education-stratified
      scores on the M-ACE and the M-MMSE, will provide a more appropriate means of
      establishing the cognitive status of patients. It is also our feeling that these
      cut-off scores will be useful across India.

PMID- 17558113
TI  - Neuronavigation in a developing country: a pilot study of efficacy and
      limitations in intracranial surgery.
AB  - CONTEXT: Neuronavigation provides a patient-specific, three-dimensional (3-D)
      anatomy for preoperative planning and intraoperative navigation. However, the
      initial and maintenance costs are quite prohibitive, especially in the Indian
      scenario. AIMS: To study the efficacy and limitations of neuronavigation,
      especially in the Indian scenario. SETTINGS AND DESIGN: A prospective
      nonrandomized study. MATERIALS AND METHODS: A total of 121 patients underwent
      intracranial surgery from 2002-2006, in which neuronavigation was used. In this,
      the initial part, we studied the efficacy and limitations of neuronavigation in
      the initial 37 patients. The efficacy of the image guidance was graded according
      to a point's scale in which points were awarded ranging from 0 to 3. Cranial
      image guided score (IGS) was calculated by the summation of grading during
      designing the flap/burr hole, delineation of the intraoperative anatomy,
      navigation and access to the lesion and resection / biopsy of the lesion or
      completion of the procedure. The scoring ranged from 0-12 and the utility of IGS
      in cranial neurosurgical procedures was calculated based on the total points for
      each surgery. RESULTS AND CONCLUSION: Cranial image guidance was useful in a
      variety of operative steps. Intraoperative approach and navigation was relatively
      easier with an increase in perception of safety. Limitations of IGS include
      learning curve, cost and the phenomenon of brain shift. Drawbacks of the study
      included that this was a subjective rather than a truly objective study and the
      relatively lesser number of patients. We hope to conduct a larger study with
      randomization but the question of ethical approval would be a primary concern.

PMID- 17558114
TI  - Sarcoglycanopathies: a clinico-pathological study.
AB  - BACKGROUND: Limb girdle muscular dystrophy (LGMD) is a heterogeneous group of
      disorders characterized by limb girdle weakness. There are no clear clinical
      features that distinguish various types of LGMD. MATERIALS AND METHODS: We
      studied 26 patients with chronic progressive weakness in limb girdle distribution
      without early facial involvement with muscle biopsies suggestive of
      dystrophy/myopathy and positive for dystrophin antibodies. Immunohistochemistry
      studies of muscle biopsies were done on all patients to classify different types
      of sarcoglycanopathies. RESULTS: The mean age of presentation was in the third
      decade. There were 14 male and 12 female patients. The common pattern of
      inheritance was autosomal recessive, seen in 53.8%. The more frequent type of
      LGMD was sarcoglycanopathy (SGP) (53.8%). Amongst the SGPs, alpha-SGP (26.9%) was
      the most common followed by beta-SGP (15.3%), gamma-SGP (3.8%) and delta-SGP
      (7.6%). Calf hypertrophy was noted in 53.5% of LGMD and 57.1% of SGPs, extensor
      digitorum brevis hypertrophy in 42% of LGMD and 35.7% of SGPs, winging of scapula
      in 39.2% of the LGMD group and 35.7% of the SGPs, valley sign in 28.5% of the
      LGMD group and 21.4% of the SGPs. Hip abductor sign was positive in 71.4% of LGMD
      and 64.2% of SGPs. Differential weakness of knee flexors was more common in SGP
      (57.1%). The mean creatine phosphokinase (CK) value was 2519IU/L and was elevated
      in 92.8% patients. Muscle biopsy showed a dystrophic pattern in 75% of LGMD and a
      myopathic pattern in the remaining. Symptomatic cardiac involvement was seen in
      one patient. ECG changes were seen in 44% of LGMD patients and 50% of the SGP.
      The common changes noted were T wave inversion in V1, V2 (16%), left ventricular
      hypertrophy LVH (12%) and right bundle branch block (RBBB) in 12% of the LGMD
      group. CONCLUSION: Sarcoglycanopathy is a more frequent form of LGMD whereas
      alpha type is the most common among the SGP. The four types of SGP do not differ
      in the pattern of muscle involvement. A relatively earlier onset, selective
      weakness of knee flexors and a very high CK may help differentiate SGP from other
      forms of LGMD. Immunohistochemistry is very useful in classifying the different
      types of LGMD prior to genetic analysis.

PMID- 17558115
TI  - The correlation of carotid plaque pathohistologic features and neurological
      symptoms: a meta-analysis of observational studies.
AB  - OBJECTIVE: To investigate the association between the pathological features of
      carotid plaque and ipsilateral symptoms of cerebral ischemia. MATERIALS AND
      METHODS: We sought to identify clinical observational studies comparing the
      incidence of pathological features between symptomatic and asymptomatic carotid
      plaques in terms of ulceration, thrombosis and intraplaque hemorrhage (IPH),
      published between 1996 and 2006. A search on, PubMed was supplemented by a review
      of bibliographies of relevant articles and lists of references in it. Odds ratios
      (OR) for the presence of each feature as a role in the pathogenesis of
      neurological events were calculated and combined by a meta-analysis. RESULTS: We
      integrated 16 clinical studies totaling 2839 plaques harvested at endarterectomy
      procedures. The reported incidence for each feature was highly variable. The
      methods in defining ulceration, thrombosis and IPH were very heterogeneous. The
      time intervals between the latest onset of ischemic symptoms and pathological
      examinations varied greatly. Overall, the incidence of ulcerated plaques in the
      symptomatic group were significantly higher than that in the asymptomatic group
      (study number, n=10; OR, 2.32; 95% CI, 1.90-2.83. A random-effect model was
      performed among studies regarding surface thrombosis because an apparent trend
      for heterogeneity was observed (n=6; OR, 1.57; 95% CI, 0.68-3.64). There was no
      difference with respect to IPH between the two groups (n=11; OR, 1.09; 95% CI,
      0.91-1.32). CONCLUSIONS: Ulcerated carotid plaque is significantly correlated
      with the production of neurological events, whereas thrombosis fails to correlate
      with ischemic symptoms because of the presence of substantial heterogeneity. The
      association between IPH and clinical presentations is less clear.

PMID- 17558116
TI  - Drug compliance after stroke and myocardial infarction: a comparative study.
AB  - BACKGROUND: Stroke and myocardial infarction (MI) are both life-threatening
      diseases of vascular origin with a tendency to recur. In both conditions, risk of
      recurrence is reduced through similar drug regimens. AIM: To determine if
      compliance with prescribed medication after stroke or MI was similar in the two
      populations. SETTING AND DESIGN: Retrospective data collection and cross
      sectional telephonic survey of patients discharged from a single academic medical
      center. MATERIALS AND METHODS: Adult patients consecutively discharged over a two
      year period with a diagnosis of first-ever stroke (ischemic or hemorrhagic) or
      first-ever MI (ST-elevation) were identified through ICD-9 codes. Clinical
      details were abstracted from hospital records. Medication compliance was assessed
      through a structured telephone interview. STATISTICAL ANALYSIS: Bivariate
      analysis using Chi-square and Fisher exact tests, to determine the prevalence of
      noncompliance in stroke versus MI patients and differences in baseline
      characteristics and multivariate analysis with logistic regression to determine
      independent predictors of noncompliance. RESULTS: Follow-up data was collected
      for 298 stroke and 275 MI patients. Compliance was lower in stroke patients (68%
      stroke patients compliant with at least half their discharge prescriptions versus
      90% MI patients; P < 0.001). Literacy and post-discharge follow-up were
      associated with greater compliance (P < 0.05 for both). Compliance was highest
      with anti-hypertensive drugs (98% after MI, 78% after stroke), followed by anti
      platelet agents (94% after MI, 75% after stroke) and anti-lipid agents (70% after
      MI, 59% after stroke). Patients reported simply not feeling the need, acquiring
      fresh medical advice or a perceived lack of benefit, as reasons for not complying
      with their discharge prescriptions. CONCLUSIONS: Although similar drugs are
      involved, compliance with prescribed regimens is appreciably lower after stroke
      than after MI. Our findings underscore the need for better patient education
      regarding secondary prevention after stroke.

PMID- 17558117
TI  - New-onset acute symptomatic seizure in a neurological intensive care unit.
AB  - OBJECTIVE: New-onset acute symptomatic seizures can be the presenting feature of
      acute neurological diseases. The etiological spectrum of new-onset acute
      symptomatic seizures and outcome may be different in developing countries when
      compared to developed countries. AIM: To study the clinical profile of new-onset
      acute symptomatic seizures as the first presenting event in patients with acute
      neurological illness in a neurological intensive care unit (NICU) in a developing
      country. SETTINGS AND DESIGN: Prospective study in a NICU in a tertiary care
      hospital. MATERIALS AND METHODS: Consecutive patients with acute symptomatic new
      onset seizure admitted to NICU in a tertiary care hospital over a period of 28
      months. The etiology was determined by neuroimaging and appropriate
      investigations including cerebrospinal fluid examination. RESULTS: Of the 3,151
      admissions, 66 (2.1%) were related to new-onset acute symptomatic seizures as the
      first presentation. The mean age was 49.07 + 20.20 years. Tonic-clonic,
      generalized tonic-clonic or partial seizure with or without secondary
      generalization were the seizure type. At presentation 52 (79%) patients had
      single seizure, 10 (15%) patients had seizure clusters and four (6%) patients
      presented with status epilepticus (SE). The major etiological risk factors were
      central nervous system (CNS) infections (32%), metabolic disorders (32%) and
      cerebrovascular diseases (21%). In the NICU 10 (15%) patients had early seizure
      recurrence and three (4.5%) developed SE. Of these 13 patients, in nine (69%)
      patients the pathology was infection-related and the other commonality was
      involvement of cortical gray matter. Factors associated with seizure recurrence
      or SE were focal cerebral lesions involving cortical gray matter or diffuse
      cerebral pathology, meningoencephalitis. In 69% of these patients the pathology
      was infection-related. There were only two deaths, both in patients with SE and
      related to the underlying etiology. CONCLUSION: The risk of seizure recurrence
      and SE after the first acute symptomatic seizure is likely to be high in patients
      with acute focal cerebral lesions and diffuse CNS infections. The commonality in
      both the pathologies is cortical gray matter involvement.

PMID- 17558118
TI  - Incidence of recurrent stroke in primary care during preventive treatment based
      on perindopril with or without indapamide.
AB  - BACKGROUND: Although the risk reduction of recurrent stroke with angiotensin
      converting enzyme-inhibitors with or without a diuretic has been demonstrated
      under randomized double blind conditions of the PROGRESS study, it is unclear
      whether the benefit is reflected in primary care practice and in populations with
      different demographic and clinical characteristics. AIM: To assess the effect and
      acceptability of perindopril with or without indapamide prevention of recurrent
      stroke, as reflected by its incidence. SETTING AND DESIGN: Multicentre,
      prospective, observational study in the setting of primary care throughout India.
      MATERIALS AND METHODS: Patients with a stable stroke or transient ischaemic
      attack (TIA) received a 12-month perindopril +/- indapamide-based regimen,
      similar to that used in PROGRESS. The principal outcome was the annual incidence
      of recurrent stroke. STATISTICAL ANALYSIS: Summary statistics and the Kaplan
      Meier procedure. RESULTS: The mean age of 298 patients was 58.3 years (SD=12.6).
      229 (77.5%) had an ischaemic stroke; 231 (77.5%) were hypertensive; 200 (85.5%)
      were receiving aspirin and 81 (27.2%) statins. During the 12-month perindopril
      based treatment, there were 8 (2.7%) recurrent strokes, with a Kaplan-Meier
      estimate of strokes plus TIA of 3.3% (95% CI, 1.0-5.6). CONCLUSIONS: The
      incidence of recurrent stroke is similar to that observed under double blind
      randomized conditions in the treatment arm of the PROGRESS study. This suggests
      that perindopril +/- indapamide-based prevention may be effective in reducing
      risk of recurrent stroke, (although the uncontrolled study design does not
      actually demonstrate this), in the setting of day-to-day clinical practice and
      among patients with different demographic and clinical characteristics than the
      PROGRESS population.

PMID- 17558119
TI  - Two measurement methods of motor ulnar nerve conduction velocity at the elbow: a
      comparative study.
AB  - BACKGROUND: Electrodiagnostically, localization of ulnar nerve lesions, which
      commonly occurs at the elbow, is sometimes problematic. Measurement of motor
      ulnar nerve conduction velocity (NCV) at the elbow is amongst the most popular
      techniques to diagnose ulnar neuropathy. In this method, recording from the first
      dorsal interosseous muscle (FDI) is suggested to be more sensitive than the
      abductor digiti minimi (ADM). However, the criterion for abnormality is based on
      the normal values recorded from ADM. AIMS: To determine the normal values of
      Ulnar motor NCV using FDI and ADM and the difference between the values obtained
      from FDI and ADM. Additionally, to measure the amount of reduction of NCV across
      the elbow for each recording site. MATERIALS AND METHODS: This was a cross
      sectional study performed on 50 healthy volunteers (100 nerves). All subjects
      were in the same condition regarding joint position and surface hand temperature.
      We recorded ulnar NCV at forearm and across the elbow with recording electrode on
      both FDI and ADM, simultaneously. RESULTS AND CONCLUSIONS: The mean NCV at the
      elbow recorded from ADM and FDI were 62.65 +/- 7.62 m/s and 60.49 +/- 7.42 m/s
      respectively, showing significant difference. The ulnar minimum normal NCVs
      recorded from ADM and FDI were 47.4 m/s and 45.6 m/s, respectively. If the normal
      values of ADM are used as the basis for recording from FDI, it could lead to
      false-positive diagnosis of cases suspicious of ulnar neuropathy. Therefore it is
      preferred to use the normal values of FDI itself while recording.

PMID- 17558120
TI  - Spontaneous extrusion of guglielmi detachable coils from anterior communicating
      artery aneurysm.
AB  - Recurrence of coiled aneurysm usually due to coil compaction is a known
      phenomenon. Extent of recurrence and its relation to re-bleeding is not known.
      The authors report a case of spontaneous asymptomatic extrusion of guglielmi
      detachable coils from the dome of a previously ruptured anterior communicating
      artery aneurysm two years after the initial endovascular obliteration. The
      initial aneurysm had a suitable neck-aspect ratio for endovascular obliteration
      with uncomplicated coiling procedure. Extreme degree of coil compaction with
      subsequent expulsion of the coils from the dome due to water-hammer effect of
      blood flow is thought to be the main pathogenic mechanism of this rare but
      worrying complication. Surgical management includes clipping at the neck ensuring
      complete obliteration of the aneurysm. Postoperative angiogram to confirm its
      satisfactory obliteration is advised.

PMID- 17558121
TI  - Late intrathoracic relapse of pineal germinoma connected to intraspinal canal.
AB  - Extraneural metastases of intracranial germinoma are rarely reported. The authors
      describe the first case of metastatic lung germinoma of the thoracic spine. A 27
      year-old man presented with right shoulder pain and right upper limb weakness. He
      had a history of repetitive radiation therapy - nine (whole-abdomen; 15Gy), 12
      (whole brain; 30Gy, whole spine 42Gy) and 14 years ago (local; 32Gy) - for
      abdominal metastasis, temporal and fourth ventricle metastasis and spinal
      dissemination and metastatic pineal germinoma, respectively. Magnetic resonance
      imaging revealed a lung mass invading the thoracic spine that was diagnosed as a
      germinoma by tumor biopsy. He was treated by irradiation with 54Gy and two cycles
      of chemotherapy with cisplatin and etoposide. He did not have any sign of tumor
      eight years later.

PMID- 17558122
TI  - Status epilepticus associated with initiation of theophylline in an elderly
      patient with diabetic ketoacidosis.
AB  - An 80-year-old man with a history of Type 2 diabetes mellitus was hospitalized
      due to generalized convulsive status epilepticus. Initially, hyperglycemia and
      ketoacidosis were diagnosed, but his seizures were refractory to the medical
      treatment. Additionally, a high level of serum theophylline (29.1 mg/mL) was
      detected. Following detoxification of theophylline by oral activated charcoal,
      the patient regained consciousness and was free from seizures without
      antiepileptic drug treatment. Brain magnetic resonance imaging revealed subacute
      subdural hematomas at the bilateral occipital hemispheres. This case suggests
      that theophylline toxicity may be a predisposing factor for seizures in patients
      with a history of traumatic brain injury in spite of the presence of diabetic
      ketoacidosis that may have an anticonvulsant action.

PMID- 17558123
TI  - Extensive meningoencephalitis, retrobulbar neuritis and pulmonary involvement in
      a patient of neurobrucellosis.
AB  - We report an unusual case of neurobrucellosis who presented with headache, vision
      loss, confusional state, retrobulbar neuritis and left hemiparesis. Neuroimaging
      studies showed features of ischemic infarct and white matter abnormalities.
      Pulmonary involvement in form of lobar pneumonia of left basal lobe was another
      unusual manifestation. Diagnosis was based on the rising titers of antibrucella
      antibody. Patient showed remarkable improvement on triple drug therapy in form of
      doxycycline, rifampicin and streptomycin.

PMID- 17558124
TI  - Parry Romberg's disease with intractable partial epilepsy.
AB  - Parry Romberg's syndrome is an uncommon disorder characterized by atrophy of skin
      and subcutaneous tissue of one side of face. It has neurologic sequel. The
      commonest of which is epilepsy. Here, we present a 17-year old girl with features
      of Parry Romberg's disease with intractable epilepsy. Her seizures have stopped
      with systemic corticosteroids. This treatment response, together with previous
      reports is suggestive of an autoimmune basis to this disorder. Thus the epilepsy
      in some such cases may be steroid responsive.

PMID- 17558125
TI  - Sudden visual loss due to posterior ischemic optic neuropathy following
      craniotomy for a ruptured intracranial aneurysm.
AB  - The authors report a rare case of acute ipsilateral blindness that occurred after
      a standard fronto-temporal craniotomy for aneurysm in supine position. Posterior
      ischemic optic neuropathy caused by external pressure on the ipsilateral eye, its
      differentials and subsequent medico-legal implications are discussed.

PMID- 17558126
TI  - The neuroleptic malignant syndrome: a report of 14 cases from North India.
AB  - Neuroleptic malignant syndrome (NMS) is a rare, life-threatening but potentially
      treatable condition. This study was performed to investigate the clinical
      spectrum, antecedent events and outcome of NMS patients admitted in the Neurology
      department of a large teaching hospital of North India. Fourteen cases of NMS
      were taken after a thorough search during a three-year period (May 2000 to April
      2003). The Incidence of NMS was 1.40/ 1000 patients treated with neuroleptics and
      mortality rate was 14.28%. Amongst the neuroleptics Haloperidol (parenteral) was
      implicated as a most common drug for NMS in 57% of patients. An association with
      coexisting precipitating illness was clearly recorded in 71.4% patients. All the
      recorded patients of NMS received 500-700 mg CPZ equivalent/day of neuroleptics.
      NMS as an indiosyncratic phenomenon was noticed in 28% patients. 85.7% responded
      to dopaminergic drugs along with supportive treatment and showed partial or
      complete recovery within 7-14 days. In those with partial recovery residual
      deficits included Parkinsonian features, depression and diaphoresis in a small
      percentage of patients.

PMID- 17558127
TI  - Intraoperative high field magnetic resonance imaging in neurosurgery: our initial
      experience with the brain suite.
AB  - We present our initial experience with the high field (1.5T) intra-operative
      magnetic resonance imaging, the operating room set-up, our initial cases, the
      difficulties we faced and how this tool affected a change in the surgical
      strategy intra-operatively and finally our results. 11 patients were operated on
      from June 1st to August 1st 2006 of which there were astrocytomas (7), pituitary
      adenoma (1), craniopharyngioma (1) and meningiomas (2) Localization and lesion
      targeting were accurate, intra-operative imaging helped to assess the resection
      volumes, enable corrections for brain shift, perform further tumor resection at
      the same sitting and help preserve eloquent cortical areas. Gliomas formed 63.6%
      of the tumors operated on and in 71.4% of these, our surgical strategy changed
      intra-operatively. Meningiomas formed 9.1% of the tumors operated and image
      guidance enabled a minimally invasive approach, although no change in our
      surgical plan was required. One pituitary adenoma and a craniopharyngioma were
      also operated on with good outcome.

PMID- 17558128
TI  - Stroke and thrombolysis in India.

PMID- 17558129
TI  - Thrombolysis with tissue plasminogen activator: protocol violation is not an
      option.

PMID- 17558130
TI  - Preoperative hypoxemia in a patient for elective aneurysm clipping: which one to
      be managed on priority?

PMID- 17558131
TI  - Brachial plexopathy due to breast cancer metastases.

PMID- 17558132
TI  - Axonal neuropathy caused by epothilone B.

PMID- 17558133
TI  - Invited commentary. The correlation of carotid plaque pathohistological features
      and neurological symptoms: a meta-analysis of observational studies.

PMID- 17558134
TI  - Indolent extranodal marginal zone lymphoma of the meninges producing chronic
      cerebral venous occlusion.

PMID- 17558135
TI  - Phenytoin-induced toxic epidermal necrolysis in a neurosurgical patient.

PMID- 17558136
TI  - Osteochondroma of basi-occiput.

PMID- 17558137
TI  - Simultaneous thalamic and cerebellar hypertensive haemorrhages.

PMID- 17558138
TI  - 'Parietal wasting' and dystonia secondary to a parasagittal mass lesion.

PMID- 17558139
TI  - Brain magnetic resonance imaging unveils the history of carbon monoxide
      poisoning.

PMID- 17558140
TI  - Nonheme-iron histochemistry for light and electron microscopy: a historical,
      theoretical and technical review.
AB  - We reviewed the methods of nonheme-iron histochemistry with special focus on the
      underlying chemical principles. The term nonheme-iron includes heterogeneous
      species of iron complexes where iron is more loosely bound to low-molecular
      weight organic bases and proteins than that of heme (iron-protoporphyrin
      complex). Nonheme-iron is liberated in dilute acid solutions and available for
      conventional histochemistry by the Perls and Turnbull and other methods using
      iron chelators, which depend on the production of insoluble iron compounds.
      Treatment with strong oxidative agents is required for the liberation of heme
      iron, which therefore is not stained by conventional histochemistry. The Perls
      method most commonly used in laboratory investigations largely stains ferric
      iron, but stains some ferrous iron as well, while the Turnbull method is specific
      for the latter. Although the Turnbull method performed on sections fails in
      staining ferrous iron or stains only such parts of the tissue where iron is
      heavily accumulated, an in vivo perfusion-Turnbull method demonstrated the
      ubiquitous distribution of ferrous iron, particularly in lysosomes. The Perls or
      Turnbull reaction is enhanced by DAB/silver/gold methods for electron microscopy.
      The iron sulfide method and the staining of redox-active iron with H(2)O(2) and
      DAB are also applicable for electron microscopy. Although the above histochemical
      methods have advantages for visualizing iron by conventional light and electron
      microscopy, the quantitative estimation of iron is not easy. Recent methods
      depending on the quenching of fluorescent divalent metal indicators by Fe(2+) and
      dequenching by divalent metal chelators have enabled the quantitative estimation
      of chelatable Fe(2+) in isolated viable cells.

PMID- 17558141
TI  - Ultrastructural dynamics of the human endometrium from 14 to 22 weeks of
      gestation.
AB  - In order to elucidate the ultrastructural dynamics of endometrium
      differentiation, uterine samples of fetuses aged 14 to 22 weeks of gestation (WG)
      were analyzed. Samples were processed for light (LM), transmission (TEM) and
      field-emission scanning electron microscopy (FE-SEM). Initial stratification of
      the uterine wall occurred at 14 WG: endometrial, myometrial, and perimetrial
      primordia were identified. At this age, the endometrial epithelium was simple
      columnar to pseudostratified and consisted of microvillous cells. Blood
      capillaries developed mainly in the stroma and between the myometrium and
      perimetrium primordia. At 18-20 WG the endometrial epithelium became clearly
      pseudostratified, with active ciliogenesis and a predominance of microvillous
      cells. Primordia of tubular glands were present at 20 WG. Microvillous cells
      still predominated in the endometrial epithelium at 21-22 WG and showed
      morphological features of apoptosis. The endometrial stroma at this stage was
      organizing into a thick lamina propria provided with subepithelial capillary
      plexuses. However, the stroma was formed by still undifferentiated mesenchymal
      cells during the whole period of study. Our data showed that the epithelial
      differentiation and distribution in the uterus occur in the human fetus in a
      similar way as in the adult. The above events are likely the expression of an
      early developmental patterning and related to future reproductive processes, such
      as the regulation of gamete passage and blastocyst implantation. Because the
      structure of the adult uterus is determined by the degree of paramesonephric duct
      fusion, septum absorption, and differentiation of the uterine primordial layers,
      our study may contribute toward clarifying to normal urogenital development.

PMID- 17558142
TI  - Changes in the rat subcutaneous connective tissue after saline and histamine
      injection in relation to fluid storage and excretion.
AB  - An experimental design was developed for morphometric analysis of the
      subcutaneous connective tissue after the subcutaneous injection of 0.1 ml of
      saline or a histamine solution (0.01, 0.1 or 1% histamine dihydrochloride in
      saline). The subcutaneous connective tissue of 4-week-old rats, originally 170.0
      +/- 13.6 mum in thickness, swelled 5.2-fold at 15 min, 3.0-fold at 2 h, and 1.2
      fold at 6 h after the injection of saline. The total cross sectional area of both
      blood and lymphatic vessels increased when compared to that at pre-injection
      (0.0186 +/- 0.0030 mm(2) in 6-mm-long specimen), 1.4-fold at 15 min, 2.2-fold at
      2 h, and 1.1-fold at 6 h post-injection, while the total number of these vessels
      increased 1.1-fold at 2 h. The total cross sectional area of lymphatic vessels
      (0.0006 +/- 0.0002 mm(2) in 6-mm-long specimen) alone surged 7.7-fold at 15 min,
      4.8-fold at 2 h, and 7.3-fold at 6 h. Collagen fibers were respectively highly,
      moderately, and mildly disorganized in arrangement at 15 min, 2 h, and 6 h after
      the saline injection. Histamine elicited an earlier, longer, and more pronounced
      vasodilatation, particularly at high concentrations. The transvascular
      permeability of Evans blue increased depending on the concentration of histamine.
      These findings indicate that the subcutaneous connective tissue has the ability
      to expand and store a considerable amount of fluid and reversibly returns to
      normal steady-state conditions by increasing fluid excretion into the blood and
      lymphatic vessels. It was also strongly suggested that the blood vessels are
      deeply involved in the excretion and volume regulation of the tissue fluid.

PMID- 17558143
TI  - Platinum blue as an alternative to uranyl acetate for staining in transmission
      electron microscopy.
AB  - This paper introduces an aqueous solution of platinum blue (Pt-blue) as an
      alternative to uranyl acetate (UA) for staining in transmission electron
      microscopy (TEM). Pt-blue was prepared from a reaction of cis-dichlorodiamine
      platinum (II) (cis-platin) with thymidine. When Pt-blue was dried on a microgrid
      and observed by TEM it showed a uniform appearance with tiny particles less than
      1 nm in diameter. The effect of Pt-blue as an electron stain was then examined
      not only for positive staining of conventional ultrathin resin sections and
      counterstaining of post-embedding immuno-electron microscopy but also for
      negative staining. In ultrathin sections of the rat liver and renal glomerulus,
      Pt-blue provided good contrast images, especially in double staining combined
      with a lead stain (Pb). Almost all cell organelles were clearly observed with
      high contrast in these sections. Glycogen granules in the hepatic parenchymal
      cells were particularly electron dense in Pt-blue stained sections compared with
      those treated with UA. In longitudinal and transverse sections of budding
      influenza A viruses, a specific arrangement of rod-like structures, which
      correspond to the ribonucleoprotein complexes, was clearly shown in each virion
      stained with Pt-blue and Pb. When post-embedding immunoelectron microscopy was
      performed in ultrathin sections of HeLa cells embedded in Lowicryl K4M, the
      localization of Ki-67 protein was sufficiently detected even after Pt-blue and Pb
      staining. The present study also revealed that Pt-blue could be used for the
      negative staining of E. coli, allowing the visualization of a flagellum. These
      findings indicate that Pt-blue is a useful, safe, and easily obtainable electron
      stain that is an alternative to UA for TEM preparations.

PMID- 17558144
TI  - Retrograde infection of precerebellar nuclei neurons by injection of a
      recombinant adenovirus into the cerebellar cortex of normal and reeler mice.
AB  - The reeler mouse is an autosomal recessive mutant mouse caused by mutation of the
      reelin gene and characterized by cerebellar ataxia. To determine whether the
      distribution pattern of precerebellar nuclei neurons in the brainstem of the
      reeler mouse changes, we injected a small volume of a replication-defective
      recombinant adenovirus carrying E. coli beta-galactosidase (lacZ) into the
      cerebellar cortex of normal and reeler mice. Five days later, the mice were
      transcardially perfused by a fixative solution. X-gal staining of coronal or
      sagittal sections of the brainstem revealed that many origins for
      reticulocerebellar, cuneocerebellar, trigeminocerebellar, and pontocerebellar
      projections were retrogradely labeled, but only a few olivocerebellar neurons
      were labeled. Retrogradely labeled neurons in the lateral reticular nucleus
      tended to locate more laterally and be more condensed into a small compartment in
      the reeler compared with their normal counterparts. Retrogradely labeled neurons
      in the external cuneate nucleus were more dorsally shifted in the reeler mice
      compared with their normal counterparts. We could not find any differences
      between the normal and reeler mice in the distribution patterns of their
      trigeminocerebellar projection neurons. Retrogradely labeled pontocerebellar
      neurons in the basilar pons of the reeler mouse were reduced in number compared
      with their normal counterparts in addition to being more ventrally and laterally
      shifted. These findings strongly suggest that the migration of some precerebellar
      nuclei neurons from the rhombic lip to their final loci may be obstructed in the
      reeler mice.

PMID- 17558145
TI  - Diverse effects of c-src deficiency on molar tooth development and eruption in
      mice.
AB  - C-src deficiency is characterized by osteopetrosis due to impaired bone
      resorption by hypofunctional osteoclasts and the resultant failure of tooth
      eruption. In preliminary observations, we frequently encountered erupted molars
      in c-src deficient mice unlike in other osteopetrotic animals. Here we examine
      the effects of c-src deficiency on the development of molar teeth with an
      emphasis on the spatial relation of growing teeth with the surrounding bones. In
      c-src deficient mice, the magnitude of tooth impaction differed considerably
      among the types of molars; all maxillary 1st molars were totally impacted deep in
      the alveolar sockets, whereas most mandibular 1st molars fully erupted into oral
      cavity. Distribution of osteoclasts in the alveolar bone was identical among all
      types of molars, and electron microscopy revealed signs of bone resorbing
      activity in these osteoclasts despite the absence of a ruffled border. From early
      development, the alveolar space was much narrower in the upper molar tooth germs
      than in the lower ones in both wild type and homozygous animals, and particularly
      so in the upper 1st molars. Current observations thus indicate a significant
      contribution of "hypofunctional osteoclasts" in c-src deficient mice in molar
      tooth development except for the upper 1st molars, which appear to require highly
      functional osteoclasts to gain sufficient space for them to grow normally. Taken
      together, these findings on the seemingly tooth-type specific effects of c-src
      deficiency on the development and eruption of molar teeth in c-src deficient mice
      can be attributed to the given differential spatial relation of the respective
      tooth germs with the surrounding bones in the presence of hypofunctional
      osteoclasts.

PMID- 17558179
TI  - A low-cost method for brain slice cultures.
AB  - Low-cost, simple procedures for organotypic tissue cultures are desirable for
      high-throughput biological experiments such as large-scale medical/drug
      screening. We present a practical and economical method to cultivate brain slices
      using hydrophilic filtration membranes. With a cost reduction of more than 90%,
      this technique allows us to prepare hippocampal slice cultures that are
      morphologically and functionally indistinguishable from those obtained by the
      widely used Millicell-CM method.

PMID- 17558180
TI  - Involvement of histamine released from mast cells in acute radiation dermatitis
      in mice.
AB  - A possible involvement of histamine in acute radiation dermatitis in mice was
      investigated. The dose of 40 Gy of gamma irradiation induced erythema and edema
      in C57BL/6 mice treated with vehicle. However, in C57BL/6 mice treated with
      chlorpheniramine and WBB6F1-W/Wv mice, erythema and edema were not observed. In
      all of these mice, epilation and dry desquamation were induced, but bepotastine
      significantly reduced the extent of these areas. These results suggest that gamma
      irradiation-induced erythema and edema were caused by histamine released from
      mast cells via histamine H1 receptor, and epilation was induced by other
      inflammatory mediators.

PMID- 17558181
TI  - Adenosine A2A-receptor stimulation inhibits lipopolysaccharide-induced
      interleukin-18 production in monocytes.
AB  - Adenosine inhibited interleukin (IL)-18 production in lipopolysaccharide (LPS)
      stimulated monocytes. The action of adenosine was antagonized by an adenosine A2A
      receptor (A2AR) antagonist and was mimicked by an A2AR agonist, suggesting that
      the stimulation of A2AR may be involved in the actions of adenosine. On the other
      hand, the stimulation of A1R and A3R inhibited the actions of A2AR stimulation,
      whereas the stimulation of A2BR had no effect on them. Activation of A2AR is
      known to increase cyclic adenosine monophosphate (cAMP) levels and to activate
      protein kinase A (PKA). A PKA inhibitor prevented the actions of A2AR
      stimulation, indicating that the action mechanism of A2AR stimulation may be via
      the activation of the cAMP/PKA pathway.

PMID- 17558182
TI  - Effects of combined oleoyl-estrone and rimonabant on overweight rats.
AB  - Oleoyl-estrone (OE) decreases appetite, maintains energy expediture, induces
      lipolysis (sparing protein), and decreases cholesterolemia and insulin
      resistance. Rimonabant (SR141716) is a cannabinoid-receptor inhibitor that
      decreases appetite and mobilizes fat. We studied whether their combination
      improves their slimming effects. Male overweight rats received daily gavages of
      5.3 mg/kg OE, 10 mg/kg rimonabant, or both drugs during 10 days. Body weight and
      composition, energy balance, adipose tissue weight, and serum hormones and
      metabolites were measured. OE halved food intake and maintained energy
      expenditure at the expense of body fat. Rimonabant effects on appetite and energy
      balance were less marked, resulting in lower lipid mobilization. OE and
      rimonabant followed the OE pattern, with no additive or synergic effects.
      Glycemia was maintained, but OE decreased insulin, GLP-1, and cholesterol, whilst
      rimonabant increased cholecystokinin and cholesterol, and decreased NEFA. Both
      drugs decreased leptin and triacylglycerols; ghrelin was unchanged. The results
      hint at different mechanisms of action of both drugs: we can assume that OE
      effects do not involve the cannabinoid pathway. OE does not seem to act, either,
      after 10 days, through the secretion of ghrelin or the intestinal appetite
      controlling peptides tested.

PMID- 17558183
TI  - Effects of a novel histone deacetylase inhibitor, N-(2-aminophenyl) benzamide, on
      a reversible hypertrophy induced by isoproterenol in in situ rat hearts.
AB  - The aim of the present study was performed to determine whether a novel histone
      deacetylase (HDAC) inhibitor, N-(2-aminophenyl)-4-{[benzyl(2
      hydroxyethyl)amino]methyl} benzamide (K-183), prevents a reversible cardiac
      hypertrophy induced by isoproterenol and improves left ventricular (LV)
      dysfunction in rats. Either isoproterenol or vehicle was infused for 3 days by
      osmotic minipump. One hour prior to the implantation of isoproterenol, K-183 or
      trichostatin A (TSA) was injected twice a day for 3 days. We recorded continuous
      LV pressure-volume (P-V) loops of in situ hearts one hour after removal of the
      osmotic minipump. LV work capability (systolic P-V area at midrange LV volume:
      PVA(mLVV)) and hemodynamics were evaluated. K-183 per se induced neither cardiac
      hypertrophy nor collagen production. Although K-183 did not prevent the
      hypertrophy, where PVA(mLVV) remained decreased, K-183, differently from TSA,
      significantly attenuated the decrease of cardiac output and the increase of
      effective arterial elastance in the hypertrophied heart. These results indicate
      that the novel HDAC inhibitor K-183 has some beneficial effects on hemodynamics,
      although K-183 has no effects of anti-hypertrophic modalities.

PMID- 17558184
TI  - Activation of spinal cholecystokinin and neurokinin-1 receptors is associated
      with the attenuation of intrathecal morphine analgesia following
      electroacupuncture stimulation in rats.
AB  - We previously demonstrated that electroacupuncture (EA) stimulation both produced
      antinociception and attenuated intrathecal (i.t.) morphine analgesia, suggesting
      that EA is capable of inducing two opposing systems, that is, opioid and anti
      opioid mechanisms. This study examined the involvement of cholecystokinin (CCK)
      in the anti-opioid effects following EA in the spinal cord. EA was applied to
      commonly used acupoints for antinociception, ST-36 located 5-mm lateral to the
      anterior tubercle of the tibia, and analgesia was assessed by the hind-paw
      pressure test in male Sprague-Dawley rats. I.t. administration of CCK (0.01 - 10
      microg) attenuated i.t. morphine analgesia (10 microg) dose-dependently. The
      attenuation of morphine analgesia following EA was reversed by i.t. proglumide, a
      CCK-receptor antagonist (0.01 microg). CCK-like immunoreactivity was increased in
      lamina I and II in the dorsal horn, and expression of spinal CCK mRNA increased
      after EA. Moreover, i.t. pretreatment with the neurokinin-1 (NK1)-receptor
      antagonist L-703,606 (18 microg) reversed both EA- and CCK-induced attenuation of
      morphine analgesia. These results suggest that CCK-mediated neural systems in the
      spinal cord may be involved in the attenuation of morphine analgesia following EA
      and that substance P-induced activation of NK1 receptors may be responsible for
      the downstream neuronal transmission of the CCK-mediated neuronal system.

PMID- 17558185
TI  - Beta2-agonist clenbuterol induced changes in the distribution of white blood
      cells in rats.
AB  - Clenbuterol [CLE: 4-amino-alpha(t-butyl-amino)methyl-3,5-dichlorobenzyl alcohol]
      is well known as a potent beta2-adrenergic agonist and non-steroidal anabolic
      drug, and thus it is generally used for sports doping and asthma therapy.
      Although the functions of immune cells such as white blood cells (WBCs) have
      shown to be modulated through beta2-adrenoceptors, the effects of CLE on immune
      responsive systems have not been elucidated systematically. Therefore, the
      effects of CLE on the number of WBCs were studied in rats. Male adult rats were
      divided into CLE-administered group and the control group to compare the number
      of total WBCs, neutrophils, monocytes, lymphocytes, eosinophils, and basophils.
      The administration (dose = 1.0 mg . kg(-1) body weight . day(-1), s.c.) of CLE
      was maintained for 30 days. CLE did not change the number of total WBCs during
      the experimental period. However, CLE increased significantly the number of
      neutrophils and monocytes, while CLE decreased drastically the number of
      lymphocytes and eosinophils. There was no significant change in the number of
      basophils between both groups. These results suggest that the administration of
      CLE induces drastic redistribution of WBCs in circulation without changing the
      number of total WBCs, and these responses of WBCs during the administration of
      CLE are sustained for at least 30 days.

PMID- 17558187
TI  - Expression pattern of sulfated glycoprotein-2 (SGP-2) mRNA in rat testes exposed
      to endocrine disruptors.
AB  - Sulfated glycoprotein-2 (SGP-2) is secreted in Sertoli cells and epididymal
      epithelial cells and plays important roles in the regulation of spermatogenesis
      and sperm maturation. To investigate whether endocrine disruptors affect
      spermatogenesis through an SGP-2-dependent mechanism, daily oral doses of
      testosterone (50, 200 and 1,000 microg/kg), flutamide (1, 5 and 25 mg/kg),
      ketoconazole (0.2, 1, 5 and 25 mg/kg), diethylhexylphthalate (10, 50 and 250
      mg/kg), nonylphenol (10, 50, 100 and 250 mg/kg), octylphenol (10, 50 and 250
      mg/kg), diethylstilbesterol (10, 20 and 40 microg/kg) or corn oil (control) were
      administered to 5 week-old, male Sprague-Dawley rats for 3 weeks. Following
      treatment with these endocrine disruptors, testicular expression of SGP-2 mRNA
      was analyzed using reverse transcription-polymerase chain reaction. Compared with
      the control, the lowest dose of testosterone (50 microg/kg/day) significantly
      increased expression of SGP-2 mRNA, whereas 200 and 1,000 microg/kg/day
      testosterone significantly decreased the expression (P<0.05). Flutamide,
      ketoconazole, diethylhexylphthalate, nonylphenol, octylphenol and
      diethylstilbesterol significantly decreased SGP-2 mRNA expression in testes at
      all doses studied, with the exception of 1 mg/kg/day flutamide (P<0.05). These
      results suggest that endocrine disruptors might decrease spermatogenesis in
      testes by decreasing expression of SGP-2 mRNA.

PMID- 17558186
TI  - Molecular dynamics of heterochromatin protein 1beta, HP1beta, during mouse
      preimplantation development.
AB  - To elucidate the molecular dynamics of HP1beta in mouse preimplantation embryos,
      we examined the localization, dynamics, and mobility of HP1beta in the
      (pro)nucleus by live cell imaging. Time-lapse observation revealed that the
      chromatin association of HP1beta is regulated in a cell cycle-dependent manner.
      HP1beta was localized in the interphase nucleus and was dynamically dissociated
      from the nucleus during the metaphase stage. The HP1beta assembly and clustered
      heterochromatin structure were both found in the nuclei of 2-cell and later-stage
      embryos. Moreover, fluorescent recovery after photobleaching analysis implied
      that HP1beta is more freely mobile in the pronucleus of the 1-cell embryo than in
      the 4-cell nucleus. These results suggest that the chromatin configuration may be
      regulated by the stability and mobility of chromatin-associated proteins
      including HP1beta during early embryonic stages.

PMID- 17558188
TI  - Relationships among estrous behavior, superovulatory response and grade 1 embryo
      sex ratio in superovulated Holstein heifers.
AB  - In this study, we first attempted to determine whether the timing of artificial
      insemination affects the sex ratio of seven-day-old embryos in superovulated
      Holstein heifers. The superovulatory treatment consisted of eight decreasing
      doses of FSH for 4 days and 2 doses of PGF(2alpha) given with the last two doses
      of FSH. The superovulated heifers were given a GnRH analogue 48 h after the first
      PGF(2alpha) treatment and were artificially inseminated 48 h (n=10) or 56 h (n=8)
      after the first PGF(2alpha) treatment. There were no significant differences in
      the percentages of unfertilized ova and transferable embryos (grades 1 to 3)
      between the two groups. The proportions of female grade 1 embryos did not
      significantly differ from the expected ratio of 50:50 (49.3% at 48 h and 52.5% at
      56 h). We then compared the estrous behavior and superovulatory responses of the
      heifers with a proportion of female embryos of 50% or less (n=7, Low group) to
      those of the heifers with a proportion of female embryos of more than 50% (n=9,
      High group). The Low group had a longer duration of estrus and a higher
      superovulatory response than the High group. These findings offer little
      encouragement for prediction of the population of female embryos collected from
      superovulated heifers. Further studies are necessary to evaluate to what degree
      maternal hormone levels are related to estrus duration and sex ratio.

PMID- 17558189
TI  - Estrogen regulates the serum level of phosphorylated prolactin in mice.
AB  - Phosphorylated prolactin (PPRL) is considered to be the most quantitatively
      important post-translationally modified form of prolactin (PRL) in rodents. We
      recently detected two different types of PPRL in the mouse pituitary gland; one
      was phosphorylated at serine and the other was phosphorylated at
      serine/threonine. Furthermore, we showed that there are obvious differences in
      the ratios between PPRLs and non-phosphorylated PRL in the pituitary gland based
      on age and sex and that estrogen influences PRL phosphorylation at serine in
      female mice. In the present study, we examined whether estradiol (E2) increases
      serine PPRL in the male pituitary gland in the same manner as in the female
      pituitary gland and examined whether PPRL is released into serum. We first
      determined the relative amounts of intrapituitary PPRLs in male mice under
      different pharmacological conditions that increased PRL secretion. The results
      indicated that treatment with E2 increases serine PPRL. We then performed two
      dimensional electrophoresis and immunoblotting analysis after immunoprecipitation
      with anti-mouse PRL antibody using male and female sera under different
      pharmacological conditions that increased PRL secretion. The results of this
      experiment indicated that there were PRLs phosphorylated at serine and
      serine/threonine in the female serum but not in the male serum. The levels of
      PPRLs in sera were greatly increased with the E2 treatment for both male and
      female sera. Furthermore, we examined the effect of E2 on PPRL synthesis in
      cultured male pituitary glands. In this experiment, we observed increased serine
      PPRL synthesis and stronger immunohistochemical staining of PRL cells with E2
      treatment. These findings suggested that serine PPRL synthesis and secretion were
      influenced by estrogen.

PMID- 17558190
TI  - Effect of histone acetylation modification with sodium butyrate, a histone
      deacetylase inhibitor, on cell cycle, apoptosis, ploidy and gene expression in
      porcine fetal fibroblasts.
AB  - The present study evaluated the effective dose of sodium butyrate (NaB), a
      histone deacetylase (HDAC) inhibitor, for determination of the level of
      enhancement of histone acetylation in porcine fetal fibroblasts (PFFs) based on
      their morphology, growth, apoptosis and cell cycle status. Cells were analyzed
      for their histone acetylation levels at H3, H4 and H2A and expression of genes
      related to histone deacetylation (HDAC1, HDAC2 and HDAC3), pro-apoptosis (Bax and
      Bak) and anti-apoptosis (Bcl-2). PFFs at passage 3-4 were cultured with 0, 0.5,
      1.0, 2.0 and 3.0 mM NaB for 96 h. NaB inhibited cell proliferation at all tested
      concentrations in a dose-dependent manner. However, there was slow cell growth
      for PFFs treated with 2.0 and 3.0 mM NaB compared with those of untreated PFFs
      and those treated with other lower concentrations (0.5 and 1.0 mM). More than 85%
      of the cells that were untreated or treated with 0.5 or 1.0 mM NaB had intact
      membranes, whereas, approximately 30% of the cells treated with 2.0 or 3.0 mM NaB
      had increased cell sizes and a more flattened and elongated appearance. NaB
      induced apoptosis in a dose-dependent manner; the rates of apoptosis were 2.5 +/-
      0.4% for 1.0 mM NaB, 7.6 +/- 1.1% for 2.0 mM NaB and 11.2 +/- 1.4% for 3.0 mM
      NaB. The chromosomal sets of PFFs treated with 0.5 and 1.0 mM NaB were normal,
      whereas a lower proportion of PFFs treated with 2.0 and 3.0 mM were classified as
      normal. NaB at 0.5 and 1.0 mM showed little effect on cell cycle. However, 2.0
      and 3.0 mM resulted in an increased cell population at the G(0)/G(1) phase.
      Increased NaB concentrations led to elevated acetylation of H3, H4 and H2A. NaB
      altered the expression of histone deacetylation and apoptosis-related genes. In
      conclusion, 1.0 mM NaB induced histone hyperacetylation in the PFFs and produced
      less deleterious effects than other concentrations; these PFFs might serve as
      suitable donors for porcine somatic cell nuclear transfer (SCNT).

PMID- 17558191
TI  - Core components of cardiac rehabilitation/secondary prevention programs: 2007
      update: a scientific statement from the American Heart Association Exercise,
      Cardiac Rehabilitation, and Prevention Committee, the Council on Clinical
      Cardiology; the Councils on Cardiovascular Nursing, Epidemiology and Prevention,
      and Nutrition, Physical Activity, and Metabolism; and the American Association of
      Cardiovascular and Pulmonary Rehabilitation.
AB  - The American Heart Association and the American Association of Cardiovascular and
      Pulmonary Rehabilitation recognize that all cardiac rehabilitation/secondary
      prevention programs should contain specific core components that aim to optimize
      cardiovascular risk reduction, foster healthy behaviors and compliance to these
      behaviors, reduce disability, and promote an active lifestyle for patients with
      cardiovascular disease. This update to the previous statement presents current
      information on the evaluation, interventions, and expected outcomes in each of
      the core components of cardiac rehabilitation/secondary prevention programs, in
      agreement with the 2006 update of the American Heart Association/American College
      of Cardiology Secondary Prevention Guidelines, including baseline patient
      assessment, nutritional counseling, risk factor management (lipids, blood
      pressure, weight, diabetes mellitus, and smoking), psychosocial interventions,
      and physical activity counseling and exercise training.

PMID- 17558192
TI  - Individualized preventive care in cardiac rehabilitation: adapted from AACVPR
      Award of Excellence Lecture, Charleston, WVa, October, 2006.
AB  - The benefits of individualizing risk factor therapies and exercise protocols in
      patients participating in early outpatient cardiac rehabilitation are reviewed.
      Risk factor intervention modules for modifications of lipid abnormalities and
      obesity are outlined. Specific individualized exercise regimens are described for
      patients characterized by the presence of obesity, older age, intermittent
      claudication, and chronic heart failure, which provide favorable outcomes related
      to risk factor measures and physical functioning. With adoption and application
      of an individualized approach for cardiac rehabilitation patients, programs are
      evolving to become secondary prevention centers for patients with established
      coronary heart disease.

PMID- 17558193
TI  - The economics of cardiac rehabilitation and lifestyle modification: a review of
      literature.

PMID- 17558194
TI  - A re-examination of the metabolic equivalent concept in individuals with coronary
      heart disease.
AB  - OBJECTIVE: The metabolic equivalent (MET) is a commonly used method of
      quantifying the energy cost and intensity of physical activity. Recent studies
      have questioned the accuracy of the well-accepted value of a MET of 3.5 mL O2.kg(
      1).min(-1). The goal of the present study was to compare the traditionally
      accepted value for 1 MET to direct measures of resting metabolic rate in a group
      of stable individuals with coronary heart disease (CHD). METHODS: The primary
      cohort consisted of 109 (60 men and 49 women) subjects with documented coronary
      heart disease and a body mass index >or=25 kg/m2. Measurements included indirect
      calorimetry, body composition, and exercise capacity (peak oxygen uptake [VO2]).
      In a substudy of 17 (10 men, 7 women) normal weight subjects (body mass index <25
      kg/m2), metabolic rate in the seated position was also measured. RESULTS: Mean
      resting value for 1 MET was a VO2 value of 2.58 +/- 0.4 mL O2.kg(-1).min(-1) for
      overweight subjects measured in the supine position and 2.84 +/- 0.59 mL O2.kg(
      1).min(-1) for normal weight individuals measured in the seated position. Caloric
      expenditure value was 0.74 +/- 0.12 kcal.kg(-1).h(-1) rather than the expected
      value of 1 kcal.kg(-1).h(-1). Values were similar between men and women. Women on
      beta-blockers had a lower resting metabolic rate (2.47 +/- 0.27 vs. 2.71 +/- 0.38
      mL O2.kg(-1).min(-1)) (P < .05) than women not on beta-blocker therapy, whereas
      there was no effect of beta-blockers in men. CONCLUSIONS: Findings confirm recent
      studies of otherwise healthy individuals and indicate that the average resting
      metabolic rate in subjects with coronary heart disease is 23% to 36% lower than
      the widely accepted value of 3.5 mL O2.kg(-1).min(-1). Results demonstrate the
      limitation of the convention of expressing energy expenditure in multiples of an
      assumed constant.

PMID- 17558195
TI  - Metabolic equivalent (MET) inflation--not the MET we used to know.

PMID- 17558196
TI  - Paraoxonase activity following exercise-based cardiac rehabilitation program.
AB  - PURPOSE: The effect of gender on paraoxonase activity was determined in 37
      ischemic heart disease patients who underwent a 12-week aerobic exercise training
      program. METHODS: Paraoxonase activity was measured by its arylesterase activity
      (spectrophotometrically, at 250 degrees C, wavelength 270 nm). RESULTS: A 16.7%
      increase in paraoxonase activity was found following the 12-week exercise
      program. In addition, there was a significant gender effect with higher mean
      paraoxonase levels among women during both preexercise (20.8%) and postexercise
      (24.2%) testing. CONCLUSIONS: Aerobic exercise training was found to be an
      effective means in inducing plasma levels elevation of the antioxidative,
      antiatherogenic paraoxonase in patients with coronary artery disease, and
      particularly in female patients.

PMID- 17558197
TI  - Effect of aerobic exercise on paraoxonase activity in a cardiac rehabilitation
      setting.

PMID- 17558198
TI  - Heart rate recovery is lower following supine exercise in asymptomatic hereditary
      hemochromatosis subjects compared with healthy controls.
AB  - INTRODUCTION: Heart rate recovery (HRR) has become an important diagnostic and
      prognostic marker in recent years. Subjects with hereditary hemochromatosis (HH)
      demonstrate arterial wall changes that reduce compliance. Arterial compliance may
      influence HRR by altering baroreceptor discharge. The purpose of the present
      study is to examine differences in HRR between subjects with HH and healthy
      controls during treadmill (TM) and supine lower extremity ergometry (SLEE)
      exercise testing. METHODS: Forty subjects with asymptomatic HH (27 men/13 women;
      mean age: 49.7 +/- 9.9 years) and 21 healthy controls (14 men/7 women; mean age:
      47.8 +/- 8.4 years) participated in this study. Each subject underwent a symptom
      limited 25-W Supine Lower Extremity Ergometry (SLEE) and Bruce TM exercise test
      within 1 week of each other. Heart rate recovery was the value obtained at 1
      minute postexercise. Peak heart rate, systolic blood pressure, and the double
      product were also obtained during each exercise test. RESULTS: Peak heart rate
      was significantly higher, whereas HRR and peak systolic blood pressure were
      significantly lower during TM compared with SLEE exercise testing in both groups
      (P < .01). A significantly lower HRR during SLEE in subjects with HH was the only
      significant difference between groups (35.4 +/- 9.0 vs. 29.2 +/- 8.5, P < .01).
      DISCUSSION: Heart rate recovery was not significantly different between HH and
      control subjects during upright exercise. However, HRR was significantly lower
      during SLEE in HH subjects compared with controls. A higher venous return during
      SLEE may have allowed for differences in arterial compliance between groups to
      influence HRR.

PMID- 17558199
TI  - Indicators of functional deficits after coronary artery bypass surgery.
AB  - The purposes of this study were to determine if ratings of difficulty or pain
      were more likely to detect deficits in activities of daily living (ADL) than
      degree of dependency and to longitudinally examine ADL in patients recovering
      from coronary artery bypass (CAB) surgery. This study included 40 patients who
      had recently undergone CAB surgery. We evaluated ADL performance using 3
      subcategories of the Functional Status Index: mobility, personal care, and hand
      activities. Subjects completed the Functional Index before, 2 weeks after, and 2
      months after CAB surgery. The percent of participants reporting difficulty or
      pain on the FSI was greater than the percent needing assistance except for hand
      activities preoperatively. Up to 65% of study participants reported deficits in
      ADL performance. In conclusion, assessments of ADL abilities that rely only on
      need for assistance may underestimate the presence of functional deficits in
      patients recovering from CAB surgery. Understanding functional level will assist
      in determining patient's need for rehabilitation services after CAB surgery.

PMID- 17558200
TI  - . . . But watch out for the weather: factors affecting adherence to progressive
      resistance exercise for persons with COPD.
AB  - PURPOSE: Exercise is an important treatment modality for persons with chronic
      obstructive pulmonary disease (COPD), but factors influencing adherence have been
      examined infrequently. The purpose of this investigation was to explore adherence
      factors to a progressive resistance exercise program for persons with COPD.
      METHODS: Persons with COPD enrolled in a 12-week trial of progressive resistance
      exercise were invited to participate in 2 semistructured qualitative interviews
      exploring program adherence. Interviews were audio-taped, transcribed, and then
      coded independently by 2 researchers. Themes relating to short-term and long-term
      adherence were then developed and described. RESULTS: Twenty-two participants
      were interviewed at the conclusion of the intervention (12 weeks), and 19
      completed a second interview at 24 weeks. Short-term exercise adherence was
      facilitated by expected outcomes, self-motivation, supervision, and group
      support, whereas health and weather factors were the major barriers to adherence.
      The barriers to exercise remained unchanged at 24 weeks despite a large decline
      in exercise adherence. Removal of environmental support at 12 weeks may have
      contributed to poor long-term exercise maintenance, with participants identifying
      group support and regular monitoring by a therapist as the most important
      strategies for maintaining exercise. CONCLUSIONS: The provision of external
      support in training program design appears important for persons with COPD.
      Longer-term adherence declined when group support and regular monitoring by a
      therapist was removed, despite the major perceived exercise barriers remaining
      unchanged. Therefore, further investigation is required to determine effective
      strategies for maximizing longer-term exercise adherence in this population.

PMID- 17558202
TI  - Goal setting in cardiac rehabilitation.

PMID- 17558203
TI  - Goals in cardiac rehabilitation: influencing factors, relation to outcome, and
      relevance of physicians' illness perception.
AB  - PURPOSE: The study attempted to identify and define subgroups of patients
      participating in cardiac rehabilitation (CR) whose CR goal profiles were similar,
      what factors influence the definition of targets for these goals, and how the
      definition of goals influenced the short-term and medium-term effects of CR.
      METHODS: Data were obtained from 2,182 patients participating in 17 CR centers in
      Germany from 2001 to 2003. The data collection instruments included a patient
      questionnaire on general health status and a case report form completed by a
      physician. RESULTS: A latent class analysis led to a 3-cluster solution including
      a patient cluster of "risk factor patients" for whom the CR goals were primarily
      reduction of blood pressure and cholesterol level; a patient cluster of
      "multimorbidity patients" with numerous interdisciplinary CR goals; and a patient
      cluster for which the goals were relatively undefined. These clusters were
      derived only from the analysis of the CR goals defined by physicians rather than
      from the analysis of the baseline health status. Goal setting in the psychologic
      area was greater than 1.5 times more likely to occur for men than for women. The
      setting of goals had no independent influence on the effects of CR. CONCLUSION:
      Findings suggest that the cognitive illness perception of the treating physician
      affects goal setting in CR.

PMID- 17558209
TI  - Fetal magnetic resonance imaging as a complement to fetal ultrasonography.
AB  - Ultrasonography is the screening method of choice for the evaluation of the
      fetus. It is safe, inexpensive, and easily performed. However, it is operator
      dependent, and evaluation may be limited because of fetal position, maternal
      obesity, overlying bone, and/or oligohydramnios. Magnetic resonance imaging is an
      alternative modality that uses no ionizing radiation, has excellent tissue
      contrast and a large field of view, is not limited by obesity or overlying bone,
      and can image the fetus in multiple planes, no matter the fetal lie. Faster
      scanning techniques allow studies to be performed without sedation in the second
      and third trimester with minimal motion artifact.

PMID- 17558210
TI  - Intraoperative ultrasonography of the brain and spine.
AB  - Intraoperative ultrasonography can play a particularly useful role in
      facilitating surgery or guiding biopsies in the brain and spinal canal. Given the
      limited access that is frequently afforded to the operating surgeon, coupled with
      lesions that may be located in deep or seemingly inaccessible locations,
      sonography performed through tiny burr holes is useful for confirming location of
      lesions, guiding biopsy, and confirming extent of resection. In the spine,
      sonography is most helpful for confirming the precise location of intradural or
      extradural masses and guiding biopsies. In this review, we describe the technical
      requirements necessary for scanning the brain and spinal cord and suggest
      scanning techniques. The spectrum of pathological entities are illustrated along
      with potential pitfalls that the inexperienced operator is likely to encounter.

PMID- 17558229
TI  - Ultrasonography of abnormal neck lymph nodes.
AB  - Ultrasonography is a useful imaging modality for assessing cervical
      lymphadenopathy in patients with head and neck carcinomas. Features of cervical
      lymph nodes using gray-scale and color and power Doppler ultrasonography can help
      to distinguish normal and reactive lymph nodes from potentially metastatic lymph
      nodes. The distinguishing features that separate abnormal from normal cervical
      lymph nodes include peripheral vascularity, shape, overall lymph node
      echogenicity, absence of hilus, presence of nodal microcalcifications, and cystic
      changes. Often, a combination of these features is needed to assign a cervical
      lymph node as being abnormal.

PMID- 17558230
TI  - Is it a fibroid? Are you sure? Sonography with MRI assistance.
AB  - Uterine fibroids are common benign lesions. Other common benign masses include
      renal cysts, renal angiomyolipomas, hepatic cysts, hepatic hemangiomas, thyroid
      cysts, adrenal incidentalomas, pulmonary granulomas and hamartomas, ovarian
      cysts, and dermoids. All these conditions, especially in asymptomatic patients,
      almost never have clinical significance. However, it is important to
      differentiate them from more sinister or even malignant lesions. In general, when
      a lesion is described as a fibroid, no further evaluation is performed. So if we
      say that a lesion is a fibroid, we have to be sure. Endometrial fibroids may
      mimic endometrial polyps or endometrial cancer. Subserous, especially
      pedunculated fibroids, may need further evaluation to differentiate them from
      ovarian pathology, colonic pathology, or even mullerian duct anomalies. Pelvic
      magnetic resonance imaging may be helpful in these cases.

PMID- 17558231
TI  - Case 1: Diagnosis: hyperreactio luteinalis complicating a normal pregnancy.

PMID- 17558232
TI  - Case 2: Diagnosis: congenital high airway obstruction syndrome.

PMID- 17558233
TI  - Case 3: Diagnosis: hereditary hemorrhagic telangiectasia.

PMID- 17558234
TI  - Case 4: Scrotal sonogram in patient with Klinefelter syndrome.

PMID- 17558235
TI  - Case 5: Diagnosis: lymph node mistaken as a partially thrombosed pseudoaneurysm.

PMID- 17558236
TI  - Case 6: Diagnosis: "focal fatty sparing" of the caudate lobe mimicking a mass.

PMID- 17558239
TI  - Pulmonary rehabilitation in lung cancer: a scientific opportunity.

PMID- 17558241
TI  - Physical exercise and endothelial progenitor cells.

PMID- 17558240
TI  - Endothelial progenitor cell mobilization and increased intravascular nitric oxide
      in patients undergoing cardiac rehabilitation.
AB  - PURPOSE: We investigated whether cardiac rehabilitation participation increases
      circulating endothelial progenitor cells (EPCs) and benefits vasculature in
      patients already on stable therapy previously shown to augment EPCs and improve
      endothelial function. METHODS: Forty-six of 50 patients with coronary artery
      disease completed a 36-session cardiac rehabilitation program: 45 were treated
      with HMG-CoA reductase inhibitor (statin) therapy > or = 1 month (average
      baseline low-density lipoprotein cholesterol = 81 mg/dL). Mononuclear cells
      isolated from blood were quantified for EPCs by flow cytometry (CD133/VEGFR-2
      cells) and assayed in culture for EPC colony-forming units (CFUs). In 23
      patients, EPCs were stained for annexin-V as a marker of apoptosis, and nitrite
      was measured in blood as an indicator of intravascular nitric oxide. RESULTS:
      Endothelial progenitor cells increased from 35 +/- 5 to 63 +/- 10 cells/mL, and
      EPC-CFUs increased from 0.9 +/- 0.2 to 3.1 +/- 0.6 per well (both P < .01), but
      11 patients had no increase in either measure. Those patients whose EPCs
      increased from baseline showed significant increases in nitrite and reduction in
      annexin-V staining (both P < .01) versus no change in patients without increase
      in EPCs. Over the course of the program, EPCs increased prior to increase in
      nitrite in the blood. CONCLUSIONS: Cardiac rehabilitation in patients receiving
      stable statin therapy and with low-density lipoprotein cholesterol at goal
      increases EPC number, EPC survival, and endothelial differentiation potential,
      associated with increased nitric oxide in the blood. Although this response was
      observed in most patients, a significant minority showed neither EPC mobilization
      nor increased nitric oxide in the blood.

PMID- 17558242
TI  - Cardiovascular responses during thermoneutral, head-out water immersion in
      patients with coronary artery disease.
AB  - PURPOSE: Water is frequently recommended as a therapeutic medium for cardiac
      patients. Reports on the cardiovascular response to immersion often differ,
      however, depending, for instance, if full or partial immersion were considered.
      The purpose of this study was to examine the cardiovascular responses to 2
      immersion protocols in 3 age and gender-matched groups of patients each with a
      specific coronary artery disease. METHODS: Fifteen patients with coronary artery
      disease entered water using a stepwise immersion (STEP) protocol (5 stages in 15
      minutes) and an immediate, complete immersion (IM) protocol (2 stages in 6
      minutes). Cardiac indices were monitored by transthoracic echocardiography. The
      heart rate was generated from the electrocardiogram, and blood pressure was
      measured using a manual mercury manometer. RESULTS: The end-diastolic volume, end
      systolic volume, stroke volume, and cardiac output decreased during STEP but
      increased during IM. As a consequence, the preload on the heart was greater
      during IM. Changes in systolic blood pressure were comparable in the 2
      situations. The immersion-related decrease of heart rate was seen during STEP,
      but not during IM. Nevertheless, the hemodynamic responses to the initial stages
      of STEP up to the ankle joint were quite similar to those observed during
      immediate immersion to the neck. CONCLUSION: The cardiovascular responses to IM
      and STEP differed between protocols and even among subgroups within the same
      protocol. The findings further suggest that isolated immersion of body
      extremities can be beneficial to patients with coronary artery disease as
      preliminary preparation before complete water immersion is undertaken.

PMID- 17558244
TI  - Prevalence of anxiety disorders in men and women with established coronary heart
      disease.
AB  - PURPOSE: Anxiety has been associated with the development and recurrence of
      coronary heart disease (CHD). The objective of this study was to estimate the
      prevalence of anxiety disorders in men and women with established CHD. METHODS:
      One hundred fifty CHD patients were evaluated via a semistructured, psychiatric
      interview to assess both current and lifetime prevalence rates of anxiety
      disorders. RESULTS: Approximately 36.0% (n = 54) of cardiac patients met the
      diagnostic criteria for at least 1 current anxiety disorder, and 45.3% (n = 68)
      presented with an anxiety disorder at some point in their lifetime. Social phobia
      and generalized anxiety disorder were the most prevalent anxiety disorders
      observed, with current prevalence rates of 21.3% and 18.7%, respectively, and a
      lifetime prevalence of 26%. In addition, the current prevalence rate of specific
      phobia was approximately 14.7%, whereas 15.3% met the lifetime criteria. Lower
      prevalence rates for panic disorder (current = 4.7%, lifetime = 5.3%),
      agoraphobia (current = 3.3%, lifetime = 4.7%), posttraumatic stress disorder
      (current = 0%, lifetime = 1.5%), and obsessive compulsive disorder (current = 0%,
      lifetime = 0.7%) were observed. Female cardiac patients evidenced significantly
      higher current (women = 58.3% vs. 25.5%, P < .001) and lifetime (women = 70.8%
      vs. men = 33.3%, P < .001) rates of anxiety disorders compared with their male
      counterparts. CONCLUSIONS: A considerable number of CHD patients evidence a
      significant history of anxiety. Greater efforts to identify and treat anxiety in
      outpatient cardiology and cardiac rehabilitation settings are needed.

PMID- 17558243
TI  - An assessment of the total amount of physical activity of patients participating
      in a phase III cardiac rehabilitation program.
AB  - PURPOSE: This study was designed to assess and characterize the physical activity
      levels and patterns of participants in a hospital-based Phase III cardiac
      rehabilitation (CR) program. METHODS: Subjects consisted of 25 men with a history
      of coronary artery disease ranging in age from 39 to 69 years who were
      participating in a Phase III CR program. Physical activity in steps and energy
      expenditure were assessed for 7 days using an accelerometer (Actigraph GT1M).
      Comparisons were made between CR days and non-CR days. In addition, physical
      activity within and outside the CR session was also compared. RESULTS: Subjects
      attended CR 3.0 +/- 1.0 d/wk (mean +/- SD) and averaged 6,907 +/- 510 steps/d
      (mean +/- SE) over 7 days. Physical activity levels were significantly higher on
      CR days versus non-CR days (10,087 +/- 631 vs 5,287 +/- 520 steps/d). Those who
      performed home exercise in addition to CR were significantly more active than CR
      only exercisers (7,993 +/- 604 vs 5,277 +/- 623 steps/d). CONCLUSIONS: These
      results suggest that a majority (52%) of CR participants met a minimal active
      goal on days they attend CR. However, only 8% reached the recommended minimum
      level of weekly physical activity. Those that did some form of home-exercise in
      addition to CR were significantly more active than the CR only exercisers.
      Although attending CR seems to help patients reach physical activity targets,
      patients should be strongly encouraged to increase their volume of physical
      activity either at the CR facility or at home. Activity monitors provide a
      practical and effective way for patients to track their physical activity levels,
      which may be helpful in reaching goals.

PMID- 17558245
TI  - The enduring impact of social factors on exercise tolerance in men attending
      cardiac rehabilitation.
AB  - PURPOSE: This study explored the influence of social support on a prognostic
      indicator among cardiac patients, exercise tolerance. The relationship of
      sociodemographic factors to social support was examined, as well as the role of
      social support as a potential mediator between sociodemographic factors and
      exercise tolerance. METHODS: Archival data were collected from a sample of 254
      men referred to cardiac rehabilitation. An exercise tolerance test was completed
      upon entry into cardiac rehabilitation, after 14 weeks, and after 9 months.
      RESULTS: Sociodemographic factors and social support reported upon entry into the
      cardiac rehabilitation program were related to initial and post-cardiac
      rehabilitation exercise tolerance, after controlling for admitting diagnoses,
      medical history, smoking, and perceived severity of illness. Overall, 28% of the
      variance in exercise tolerance was explained at baseline, 19% at 14 weeks, and
      20% at 9 months. Specifically, older individuals had poorer exercise tolerance,
      whereas those with more income had better exercise tolerance. Social support was
      positively related to exercise tolerance at all 3 times. Older men reported less
      social support than younger men did, and those with more income reported more
      social support. However, social support did not mediate the relationship between
      sociodemographic factors and exercise tolerance. CONCLUSIONS: Results support the
      potential use of broad social factors in examining the determinants of prognostic
      factors for heart patients.

PMID- 17558247
TI  - Outcome evaluation of brief psychosocial training for cardiac rehabilitation
      staff.

PMID- 17558248
TI  - Psychosocial training and cardiac rehabilitation.

PMID- 17558249
TI  - Determinants of walking exercise among individuals with intermittent
      claudication: does pain play a role?
AB  - PURPOSE: This study examined psychosocial determinants of walking exercise among
      individuals with intermittent claudication and explored perceived pain intensity
      as a moderator of the intention-behavior relationship. METHODS: Ninety-four
      participants (n = 61 m/33 f, 70.05 +/- 9.02 years) were recruited from a medical
      facility and completed baseline measures of attitudes (ie, positive or negative
      evaluation of walking exercise), subjective norms (ie, perceived social pressure
      regarding walking exercise), perceived behavioral control (ie, ease or difficulty
      for engaging in walking exercise), and intentions regarding walking exercise in
      the upcoming 4 weeks. Participants were contacted weekly by telephone for 4 weeks
      and asked to recall their walking exercise and associated perceived pain
      intensity for the preceding 7-day period. Outcome measures were participants'
      baseline intentions to walk and their reported walking exercise for 4 weeks.
      RESULTS: Attitudes, subjective norms, and perceived behavioral control
      contributed to a multiple regression model predicting 67% of the variance in
      walking intentions. Intentions and perceived behavioral control explained 34% of
      the variance in walking exercise. Perceived pain intensity was not associated
      with walking exercise and failed to moderate the intention-behavior relationship.
      CONCLUSION: Findings support the theory of planned behavior for predicting
      walking intentions and exercise among individuals with intermittent claudication
      and suggest that pain cognitions as measured in this study do not play a role in
      determining walking.

PMID- 17558251
TI  - The neuropsychologic deficits of MELAS: evidence of global impairment.
AB  - OBJECTIVE: To examine the neuropsychologic profile of MELAS (mitochondrial
      myopathy, encephalopathy, lactic acidosis, and strokelike episodes) and relate it
      to neuropathologic findings. BACKGROUND: MELAS is one of over 40 mitochondrial
      disorders. Symptoms include seizures, strokelike episodes, headaches, memory
      impairment, hemianopsia, hearing loss, short stature, diffuse limb weakness,
      exercise intolerance, nausea, and vomiting. Age of onset ranges from 2 to 40
      years. A hallmark of MELAS is normal development until the first symptoms appear.
      METHOD: Because information regarding the neuropsychologic functioning of these
      individuals is sparse, we report findings from detailed neuropsychologic
      evaluations for a 13-year-old white male and a 33-year-old African-American male
      with MELAS. RESULTS: Results revealed global patterns of deterioration in
      executive function, attention, language, memory, visuospatial, and motor
      functioning. In both patients, brain scans revealed posterior pathology in the
      absence of frontal pathology. CONCLUSIONS: We compared our findings with other
      documented cases and concluded that MELAS is characterized by a pattern of global
      deterioration. This pattern differs from that observed in other mitochondrial
      disorders. The absence of identifiable frontal lobe pathology despite the
      presence of deficits in executive functioning may be related to the distribution
      patterns of deficient mitochondria and neuronal projection patterns.

PMID- 17558250
TI  - Emotional perception deficits in amyotrophic lateral sclerosis.
AB  - OBJECTIVE: Cognitive deficits associated with frontal lobe dysfunction can occur
      in amyotrophic lateral sclerosis (ALS), particularly in individuals with bulbar
      ALS who can also suffer pathologic emotional lability. Because frontal
      pathophysiology can alter emotional perception, we examined whether emotional
      perception deficits occur in ALS, and whether they are related to depressive or
      dementia symptoms. METHODS: Bulbar ALS participants (n=13) and age-matched
      healthy normal controls (n=12) completed standardized tests of facial emotional
      and prosodic recognition, the Geriatric Depression Scale, and the Mini-Mental
      State Examination. Participants identified the basic emotion (happy, sad, angry,
      afraid, surprised, disgusted) that matched 39 facial expressions and 28 taped,
      semantically neutral, intoned sentences. RESULTS: ALS patients performed
      significantly worse than controls on facial recognition but not on prosodic
      recognition. Eight of 13 patients (62%) scored below the 95% confidence interval
      of controls in recognizing facial emotions, and 3 of these patients (23% overall)
      also scored lower in prosody recognition. Among the 8 patients with emotional
      perceptual impairment, one-half did not have depressive, or memory or cognitive
      symptoms on screening, whereas the remainder showed dementia symptoms alone or
      together with depressive symptoms. CONCLUSIONS: Emotional recognition deficits
      occur in bulbar ALS, particularly with emotional facial expressions, and can
      arise independent of depressive and dementia symptoms or comorbid with depression
      and dementia. These findings expand the scope of cognitive dysfunction detected
      in ALS, and bolsters the view of ALS as a multisystem disorder involving
      cognitive and also motor deficits.

PMID- 17558252
TI  - Clinical significance of silent cerebral infarctions in patients with Alzheimer
      disease.
AB  - BACKGROUND: Although recent advances in the epidemiology of Alzheimer disease
      (AD) suggest a strong association between vascular factors predisposing to
      cerebrovascular disease and AD, the results of many studies on the relation
      between cerebrovascular disease and AD have been yet controversial. Therefore, we
      conducted this study to clarify the relation between concomitant silent cerebral
      infarctions and the cognitive decline of AD patients. METHODS: One hundred and
      fifty subjects participated in this study: 51 patients had AD, 44 patients had AD
      with silent cerebral infarction (ADI), and there were 45 control subjects. These
      subjects received the global cognitive function testing and they were all
      evaluated with detailed neuropsychologic tests including attention, memory,
      language, and also the visuospatial and frontal function. RESULTS: Compared with
      the control group, the patients with AD and ADI demonstrated significantly
      impairments in all cognitive domains. The ADI group showed more marked impairment
      than did the AD group on the domains including the language function, the delayed
      recall test, and semantic fluency. CONCLUSIONS: ADI showed more severe cognitive
      decline than AD, indicating that cerebrovascular disease contributes to the
      severity of cognitive decline. These results suggest that prevention of
      cerebrovascular disease can play an important role in preventing the rapid
      cognitive decline of AD.

PMID- 17558253
TI  - Nonepisodic memory deficits in amnestic MCI.
AB  - OBJECTIVE: To (a) compare patients with amnestic Mild Cognitive Impairment (MCI),
      mild Alzheimer disease (AD), and a group of healthy elderly persons on
      nonepisodic memory measures; (b) examine which measures are independent of level
      of education in the groups studied. BACKGROUND: Episodic memory impairment is a
      cardinal feature of preclinical AD. However, a number of other cognitive measures
      are also sensitive to the preclinical stage of AD and deficits in multiple
      domains characterize AD several years before clinical diagnosis. MATERIALS AND
      METHODS: Patients with amnestic MCI (N=31), patients with mild probable AD
      (N=15), and healthy elderly controls (N=27) were compared on nonepisodic memory
      tasks measuring fluid intelligence, working memory, processing speed, verbal
      fluency, and visual-perceptual and motor functions. Amnestic MCI patients were
      selected based on clinical criteria and a subgroup was also selected based on
      psychometric criteria. RESULTS: Multivariate analyses of covariance, controlling
      for the effects of age, education, and sex, showed that fluid intelligence,
      working memory, processing speed, semantic fluency, visual-perceptual function,
      and complex motor function were significantly worse in the MCI than the elderly
      control group. Working memory, processing speed, semantic fluency, and complex
      motor tasks were significantly worse in the mild probable AD than the MCI group.
      The analyses were corroborated using the psychometrically derived MCI group.
      CONCLUSIONS: (a) Performance on multiple nonepisodic memory measures is affected
      in the preclinical stage of AD, indicating that broad cognitive impairment
      characterizes that stage. (b) Complex motor tasks were independent of level of
      education in our sample, and may have practical utility in the early detection of
      dementia.

PMID- 17558254
TI  - Lateral interactions and speed of information processing in highly functioning
      multiple sclerosis patients.
AB  - Visual impairment is a common feature of multiple sclerosis. The aim of this
      study was to investigate lateral interactions in the visual cortex of highly
      functioning patients with multiple sclerosis and to compare that with basic
      visual and neuropsychologic functions. Twenty-two young, visually unimpaired
      multiple sclerosis patients with minimal symptoms (Expanded Disability Status
      Scale <2) and 30 healthy controls subjects participated in the study. Lateral
      interactions were investigated with the flanker task, during which participants
      were asked to detect the orientation of a low-contrast Gabor patch (vertical or
      horizontal), flanked with 2 collinear or orthogonal Gabor patches. Stimulus
      exposure time was 40, 60, 80, and 100 ms. Digit span forward/backward, digit
      symbol, verbal fluency, and California Verbal Learning Test procedures were used
      for background neuropsychologic assessment. Results revealed that patients with
      multiple sclerosis showed intact visual contrast sensitivity and neuropsychologic
      functions, whereas orientation detection in the orthogonal condition was
      significantly impaired. At 40-ms exposure time, collinear flankers facilitated
      the orientation detection performance of the patients resulting in normal
      performance. In conclusion, the detection of briefly presented, low-contrast
      visual stimuli was selectively impaired in multiple sclerosis. Lateral
      interactions between target and flankers robustly facilitated target detection in
      the patient group.

PMID- 17558255
TI  - The negative syndrome as a dimension: factor analyses of PANSS in major
      depressive disorder and organic brain disease compared with negative syndrome
      structures found in the schizophrenia literature.
AB  - OBJECTIVE: To explore the concept of the negative syndrome as a dimensional
      entity that exists in multiple primary diagnoses, and to compare the negative
      syndrome in nonschizophrenic disorders and schizophrenia. BACKGROUND: Although
      initially considered specific to schizophrenia, the negative syndrome has
      subsequently been described in major depression, stroke, and dementia. METHOD: We
      performed an exploratory factor analysis on Positive and Negative Symptom Scale
      scores of 82 subjects with major depressive disorder and 76 subjects with organic
      brain disease (dementia or stroke). RESULTS: The examination of the resultant
      symptom clusters revealed that the structure of the negative syndrome in major
      depressive disorder and organic brain disease closely corresponded to that in
      schizophrenia literature. CONCLUSIONS: The negative syndrome may be a nosologic
      entity, which remains fairly consistent across psychotic and nonpsychotic
      diagnostic categories. Confirmatory studies are merited to determine the degree
      and strength of the similarity in structure of the negative syndrome in
      psychotic, affective, and cognitive illness.

PMID- 17558256
TI  - Impairment of decision-making cognition in a case of frontotemporal lobar
      degeneration (FTLD) presenting with pathologic gambling and hoarding as the
      initial symptoms.
AB  - OBJECTIVE: The aim of this study was to use the Iowa Gambling Task (IGT) to
      examine decision-making cognition in a patient with mild frontal variant of
      frontotemporal dementia (fv-FTD). BACKGROUND: Although fv-FTD may present with
      bizarre and dramatic behavioral changes, traditional executive tasks are
      sometimes preserved in patients with mild fv-FTD. Some evidence suggests that
      tasks assessing decision-making cognition, such as the IGT, may be sensitive to
      detect cognitive dysfunction in patients with mild fv-FTD. Here, we report a
      patient with fv-FTD who presented with bizarre behavior including hoarding,
      pathologic gambling, and abnormal sexual behavior. METHODS: A 54-year-old man who
      had been diagnosed as having fv-FTD was examined using a behavioral assessment, a
      wide range of neuropsychologic tasks, and the IGT. Brain magnetic resonance
      imaging and brain 99mTc-ethylcysteinate dimer single-photon emission computed
      tomography examinations were also performed. RESULTS: Although the patient's
      cognitive abilities were almost fully preserved for a number of traditional
      neuropsychologic tasks (memory, executive function), the IGT suggested that his
      decision-making cognition was impaired. The 99mTc-ethylcysteinate dimer single
      photon emission computed tomography examination revealed hypometabolism in
      bilateral medial frontal and orbitofrontal regions of the cerebral cortex, and
      also in the cingulate gyri. CONCLUSIONS: Our findings suggest that the IGT may be
      a sensitive tool for assessing patients with mild fv-FTD before the development
      of severe dementia. We speculate that the deficit in decision-making cognition
      observed in the present case was associated with hypometabolism in the neural
      networks of the frontal lobe and involving both the bilateral medial frontal and
      orbitofrontal regions of the cerebral cortex.

PMID- 17558257
TI  - Severe amnesic syndrome and collecting behavior after surgery for
      craniopharyngioma.
AB  - Significant neuropsychologic sequelae were induced by total removal of
      craniopharyngioma via a frontobasal interhemispheric approach. A 50-year-old
      right-handed man developed severe amnesic syndrome and collecting behavior after
      total removal of a craniopharyngioma. He had very poor results on tests of
      learning, recall, and recognition for both verbal and nonverbal tasks. Magnetic
      resonance imaging revealed damage to the bilateral mammillary bodies and
      fornices, and N-isopropyl-p-[23I]iodoamphetamine single photon emission computed
      tomography showed decreased cerebral blood flow in the bilateral frontal lobes,
      predominantly in the right, and regions around the third ventricle. The present
      case suggests that damage to the brain structures surrounding the third ventricle
      associated with surgery for craniopharyngioma may result in amnesic syndrome and
      collecting behavior. Generally, the frontobasal interhemispheric approach is the
      optimum choice for the removal of craniopharyngioma without significant sequelae
      related to the surgical method, but the risk of neuropsychologic disturbances
      must be kept in mind.

PMID- 17558258
TI  - Isolated inability to write cursively after transient ischemic attack (TIA).
AB  - OBJECTIVE: To examine the different aspects of language and its representation in
      the brain. BACKGROUND: Apractic agraphia, a form of mechanical agraphia, is
      produced by lesions in the left superior parietal lobe. However, little is known
      about the dissociation between allographic level representations for cursive
      writing and printing. METHOD: A 78-year-old right-handed patient with a history
      of transient ischemic attack was evaluated by interview, neurologic and
      neuropsychiatric examination, neuropsychologic testing, speech and language
      evaluation, and functional neuroimaging (single photon emission computed
      tomography). RESULTS: The patient exhibited a disorder strictly limited to
      cursive writing resulting from ischemic damage to parietal and occipital lobes
      bilateral. CONCLUSIONS: These findings support the assertion that printing and
      cursive writing are represented differentially and an isolated deficit in any of
      them can be the only presentation of disorder of language organization, secondary
      to brain damage in left superior parietal area.

PMID- 17558259
TI  - A patient with post-traumatic stress disorder developing stiff person syndrome:
      is there a correlation?
AB  - Stiff person syndrome (SPS) is an uncommon disorder characterized by progressive
      muscle stiffness, rigidity, and axial muscle spasms. It is presumed to be an
      autoimmune process, with glutamic acid decarboxylase antibodies present in most
      cases. Here, we present a case report of a patient diagnosed with post-traumatic
      stress disorder (PTSD) acquired by sexual trauma and by exposure to the severely
      wounded soldiers she attended as a nurse. Subsequently, she developed SPS
      confirmed by serology. The possibility of an association between PTSD and SPS is
      theorized, given their relationship to the GABAergic system. Further studies
      examining the relation between PTSD and SPS should be initiated.

PMID- 17558260
TI  - Psychosis and EEG abnormalities as manifestations of Hashimoto encephalopathy.
AB  - Hashimoto encephalopathy (HE) is a distinct form of encephalopathy, which can
      manifest itself with purely psychiatric symptoms. A 38-year-old female with
      history of rheumatoid arthritis was treated with psychotropic drugs for a couple
      of years in psychiatric structures because of the onset of depressive symptoms,
      psychoticlike manifestations, and impairment of cognitive functions. The
      electroencephalography (EEG) was characterized by general slowing with high
      voltage (2 to 3 Hz) delta biphasic and triphasic waves. Once a firm diagnosis of
      HE was made, corticosteroid treatment resulted in resolution of her psychiatric
      symptoms, marked EEG improvement, and partial improvement in her cognitive
      functions. HE should be suspected in young females with history of autoimmune
      disorders and EEG abnormalities.

PMID- 17558263
TI  - Developments in the pharmacotherapy of the overactive bladder.
AB  - PURPOSE OF REVIEW: The overactive bladder is a common and distressing condition
      that has a significant impact on the quality of life of many people worldwide.
      Anticholinergics remain the first line in pharmacotherapy, however the use of
      these agents is hindered by adverse effects and limited efficacy. Thus there is a
      need for more effective treatments. Recently, there has been a move towards
      targeting novel pathways thought to play a role in overactivity. This review aims
      to provide an insight into the recent developments in pharmacotherapy of the
      overactive bladder. RECENT FINDINGS: With recent advances in our understanding of
      the basic science of the overactive bladder it is becoming clear that the control
      of bladder functioning is far more complex than previously believed.
      Peripherally, a prominent role has emerged for the urothelium and the underlying
      suburothelium in mechanosensory control, and the role of afferent pathways in
      pathophysiology is increasingly recognized. SUMMARY: Recent research has
      highlighted several potential targets for treatment of the overactive bladder,
      particularly within the mechanosensory pathways. With the exception of botulinum
      toxin, however, few new therapies have emerged showing clinical benefits. A
      clearer understanding of the pathophysiology of the bladder will hopefully lead
      to more effective and tolerated treatments.

PMID- 17558264
TI  - Overactive bladder: an update.
AB  - PURPOSE OF REVIEW: Overactive bladder is an important lower urinary tract
      syndrome that negatively affects the quality of life of millions of people
      worldwide. Both sexes and all age groups may be affected; therefore many
      specialists, including urologists, gynaecologists, geriatricians, paediatricians,
      physiotherapists and continence advisors, are involved in the management of
      patients with overactive bladder. RECENT FINDINGS: There is ongoing research,
      both basic science and clinical trials, to establish the cause of overactive
      bladder and to determine the best method of managing patients who suffer from
      this syndrome. New theories and modified definitions of overactive bladder have
      been proposed, structured evidence-based management guidelines have been
      established, more prevalence studies have been conducted and new treatment
      strategies have emerged. SUMMARY: Overactive bladder is now recognized as a
      chronic debilitating condition that costs millions of dollars. With an ageing
      population these costs will increase, and it is necessary that health systems
      around the world recognize this. Further research into the basic science of the
      condition is required to identify the true cause of overactive bladder, allowing
      new targeted treatments to be established.

PMID- 17558265
TI  - Prolapse surgery: an update.
AB  - PURPOSE OF REVIEW: The purpose of the review is to highlight the latest
      developments in the surgical treatment of pelvic organ prolapse. RECENT FINDINGS:
      Total vaginal mesh has been developed with the intent to improve the outcome of
      pelvic floor reconstructive surgery. Two interesting papers were published in
      2006. At the short follow up available, the data appear interesting, although the
      rate of erosions is quite high. Two American teams reported their experience in
      robotic surgery for the management of sacrocolpopexy and hysterectomy. The
      published data on the use of the da Vinci system are interesting, although they
      need to be reproduced and improved in other centers. A randomized controlled
      trial suggests the efficacy of Burch colposuspension as an antiincontinence
      procedure in patients undergoing sacrocolpopexy for pelvic organ prolapse.
      SUMMARY: Total vaginal mesh and robotic surgery are major innovations in the
      field of urogynecology. Also, Burch colposuspension has proved to be an effective
      antiincontinence procedure in patients undergoing sacrocolpopexy for pelvic organ
      prolapse. Further studies are needed, however, with longer follow-up periods.

PMID- 17558266
TI  - What's new in slings: an update on midurethral slings.
AB  - PURPOSE OF REVIEW: Surgical management of female stress incontinence has
      progressed rapidly over the past decade. The purpose of this review is to provide
      up-to-date information regarding surgical outcomes of midurethral slings and to
      discuss management of sling complications. Additionally, the newer commercially
      available products will be outlined and the data comparing new versus established
      techniques will be examined. RECENT FINDINGS: Long-term data are available for
      the Tension-free Vaginal Tape procedure which demonstrates durable efficacy.
      Comparisons between the Tension-free Vaginal Tape and Suprapubic Arch sling
      procedure demonstrate no significant difference in cure rates or complications.
      In an effort to avoid the retropubic space, the transobturator slings were
      developed and short-term data suggest similar efficacy to the transabdominal
      techniques. The transobturator approach, while limiting abdominal complications,
      is not without its own complication profile. Increased experience with synthetic
      mesh in vaginal surgery has allowed for a more systematic approach to managing
      mesh erosions. SUMMARY: The literature indicates that midurethral slings, despite
      the specific approach, are efficacious and an important therapy in managing
      stress incontinence. Prospective data will be needed before the surgeon can
      determine if the new products and techniques are truly an improvement over the
      existing products or merely a proprietary modification.

PMID- 17558267
TI  - Specialist training in female urology and reconstructive urology: the UK
      experience.

PMID- 17558268
TI  - Role of prophylaxis in vesicoureteral reflux.
AB  - PURPOSE OF REVIEW: Traditional management of vesicoureteral reflux focuses on
      preventing renal complications associated with ascending urinary tract infection
      by either providing continuous antibiotic prophylaxis to sterilize the urine and
      thus prevent recurrent infection, or abolishing reflux via surgical intervention.
      This review will consider the rationale for antibiotic prophylaxis in light of
      contemporary data regarding the natural history of vesicoureteral reflux, urinary
      tract infection and renal scarring, as well as the efficacy of various treatment
      strategies. RECENT FINDINGS: Recent studies have shown that in grades I-IV
      vesicoureteral reflux, open surgical intervention compared with antibiotic
      prophylaxis is no better at preventing renal complications. Endoscopic
      subureteral injection of biomaterials has been proposed as a cost-effective,
      minimally invasive alternative to surgical or medical intervention; however,
      given the variety of materials and techniques, the literature has yet to achieve
      consensus on its efficacy. The first study to compare antibiotic prophylaxis with
      increased surveillance and prompt treatment of urinary tract infection shows no
      difference between the two approaches in low-grade (grades I-II) vesicoureteral
      reflux. SUMMARY: Recent studies have challenged the traditional paradigm of
      aggressive vesicoureteral reflux management with surgery or antibiotic
      prophylaxis. In light of these findings, pediatric urologists will need to
      reexamine treatment modalities for vesicoureteral reflux.

PMID- 17558269
TI  - Fetal myelomeningocele repair: urologic aspects.
AB  - PURPOSE OF REVIEW: The notion that earlier surgical correction of congenital
      anomalies will lead to improved outcomes permeates throughout surgical
      literature. This review critically assesses some of the urologic evaluations in
      patients who have undergone fetal repair of their myelomeningoceles. RECENT
      FINDINGS: Thus far, there are limited data to determine the effects of such a
      repair with respect to urologic outcome. Early data, though, have suggested that
      improvements are being noted in a cohort of patients who have undergone fetal
      repair of their myelomeningocele with respect to neurodevelopmental outcome and
      lower extremity neuromotor function. SUMMARY: What remains to be seen is whether
      fetal surgery and the noted changes translate into long-term improvement. The
      efforts being put forth to critically assess the outcomes of such surgery are
      laudable and yet the end analysis may still leave the question unanswered.

PMID- 17558271
TI  - Reoperative hypospadias.
AB  - PURPOSE OF REVIEW: To review recent publications on the surgical treatment of
      hypospadias failures, including prognostic factors, which may influence final
      outcome in hypospadias surgery. RECENT FINDINGS: Interim good outcomes for single
      stage dorsal inlay grafting in patients with multiple failed repairs would
      suggest a greater role for this new technique over other available options.
      Slowly emerging long-term data confirm our suspicion that a good result early on
      is not necessarily indicative of a satisfactory long-term outcome. SUMMARY:
      Hypospadias surgery remains a considerable technical challenge and improvement
      will come from the development of specialized units.

PMID- 17558270
TI  - Adolescent varicocele.
AB  - PURPOSE OF REVIEW: Adolescent varicocele is a common lesion which remains poorly
      understood. Recent research in pathophysiology and surgical management has shed
      new light on this increasingly diagnosed clinical entity. RECENT FINDINGS: Recent
      research demonstrates the potential importance of heat and oxidative stress
      patterns on testicular dysfunction with varicocele. The importance of testicular
      volume differentials as a surgical indication have been demonstrated. Surgical
      innovations have included artery sparing, often with microscopic magnification,
      and enhanced identification of lymphatics to reduce hydrocele with a laparoscopic
      approach. SUMMARY: Optimal management of adolescent varicocele is being
      clarified. A conservative, selective approach based on testicular volume
      differentials and semen analysis findings seems appropriate. Techniques affording
      artery and lymphatic sparing should be employed.

PMID- 17558272
TI  - Contemporary outcomes in bladder exstrophy.
AB  - PURPOSE OF REVIEW: The patient with bladder exstrophy presents complex surgical
      and clinical management challenges to the pediatric urologist. This review aims
      to present recent developments in the care of these patients as well as to review
      contemporary medical outcomes. RECENT FINDINGS: Most of the early literature
      pertaining to bladder exstrophy has focused on surgical techniques and
      management. In the last 10-20 years, however, there has been an increase in the
      number of publications dealing with long-term outcomes in these patients.
      Psychosexual development, sexual function and social adaptation have received as
      much attention as urinary continence status, bladder, and renal function. This
      review will examine these topics. SUMMARY: Despite the complex nature of bladder
      exstrophy, there are no well designed, prospective trials examining clinical
      outcomes in these patients. Until better trials are planned, executed and
      published, much of what we know about patients with bladder exstrophy will be
      based on retrospective observations with significant biases.

PMID- 17558273
TI  - Update on pediatric genitourinary oncology.
AB  - PURPOSE OF REVIEW: Results of collaborative studies and advances in our
      understanding of the molecular biologic events involved in children's
      genitourinary cancers continue to advance treatment. Simultaneously, newly
      released reports analyze the long-term risks of treatment. We review the most
      significant recent developments in the field. RECENT FINDINGS: New basic research
      findings are making molecular staging a reality for children with cancer.
      Patients with adverse biologic features can now be stratified to receive
      intensified therapy while others may safely be considered for diminished
      adjunctive treatment. Collaborative trials continue to accrue experience and
      refine current strategies. Studies of survivors suggest that the long-term risk
      of adverse effects associated with current chemotherapeutic and radiation
      regimens are significant. SUMMARY: Continued progress from collaborative trials
      along with advancing knowledge of the molecular biology of children's cancers
      promise to improve outcomes. Novel therapies are needed as emerging data suggest
      significant treatment-associated morbidity exists from current therapy.

PMID- 17558274
TI  - Bibliography. Current world literature. Female urology.

PMID- 17558275
TI  - Conditioning to magnetic directions.

PMID- 17558276
TI  - Role of ventral striatum in reward-based decision making.
AB  - So far, the specific role of the ventral striatum in reward-based decision making
      remains elusive. Here, we examined the role of the ventral striatum in reward
      based decision making using functional MRI and a probabilistic object reversal
      task. During decision making, activity in the ventral striatum increased
      monotonically as a function of association learning and was greatest when the
      individuals expected to be rewarded for the decision with high certainty.
      Conversely, during the reward phase, activity in the ventral striatum showed an
      inverted U-shaped modulation by learning and was greatest when uncertainty about
      the outcome was maximal. Our data indicate that, during reward-based decision
      making, the ventral striatal signal dynamically changes over time dependent on
      the phase of the reward process and on the learning status and thereby acts as a
      motivational engine for the continuation of behavior.

PMID- 17558277
TI  - Activation of extracellular-signal-regulated kinase-1/2 precedes and is required
      for injury-induced Schwann cell proliferation.
AB  - Activation of extracellular-signal-regulated kinase-1/2 (Erk1/2) by
      phosphorylation to p-Erk1/2, and proliferation of Schwann cells were investigated
      in the rat sciatic nerve by immunohistochemistry. Axotomy in vivo and culturing
      of nerve segments in vitro resulted in a rapid (30 min) increase of p-Erk1/2 in
      Schwann cells with peaks at 2 and 24 h. Proliferation measured by bromodeoxy
      uridine incorporation and immunostaining in vivo and in vitro 48 h after axotomy
      showed an increase in Schwann cell proliferation at the sites of Erk1/2
      activation. The Erk1/2 inhibitor U0126 inhibited both the increase in p-Erk1/2
      and the bromodeoxy uridine incorporation. We suggest that an increase in p-Erk1/2
      is required for nerve injury-induced proliferation of Schwann cells.

PMID- 17558278
TI  - p38 mitogen-activated protein kinase independent SB203580 block of H2O2-induced
      increase in GABAergic mIPSC amplitude.
AB  - Hydrogen peroxide may serve as a diffusible intermediary messenger under
      physiological and pathophysiological conditions. H2O2 (1 mM) increased the
      amplitude of GABAergic miniature inhibitory postsynaptic currents in substantia
      gelatinosa of the spinal cord. This effect of H2O2 was reversed by the p38
      antagonist SB203580, but not by the extracellular signal-regulated kinase 1/2
      antagonist PD98059, or the Jun N-terminal kinase antagonist, SP600125. Western
      blot analysis, however, demonstrated a maximally activated mitogen-activated
      protein kinase of the slice preparation with no further increase in the phospho
      mitogen activated protein kinase by H2O2. Confocal microscopy documented no
      occult neuronal phospho-p38 induction not detected by Western blot. We conclude
      that SB203580 blocks H2O2-induced increase in GABAergic miniature inhibitory
      postsynaptic amplitude independent of its action on p38 mitogen activated protein
      kinase.

PMID- 17558279
TI  - The rat vanilloid receptor splice variant VR.5'sv blocks TRPV1 activation.
AB  - The capsaicin receptor (VR1, TRPV1) is a ligand-gated ion channel predominantly
      expressed in peripheral nociceptors and activated by multiple noxious stimuli
      including products of inflammation. A 5'-splice variant (VR.5'sv) of TRPV1 has
      been previously isolated and found to be insensitive to noxious stimuli. We
      report in this study that coexpression of VR.5'sv with TRPV1 in Xenopus oocytes
      blocks TRPV1-mediated current responses. Oocytes expressing the inhibitory
      profile demonstrated colocalization of TRPV1 and VR.5'sv-associated
      immunostaining in the plasma membrane. TRPV1 protein expression was comparable in
      all groups. Evidence of endogenous VR.5'-splice variant-like-protein expression
      was detected in dorsal root ganglion. These results support the idea that
      coexpression of VR.5'sv or a similar variant could result in inhibitory
      modulation of TRPV1 activation.

PMID- 17558280
TI  - Involuntary capture of attention produces domain-specific activation.
AB  - In this study, we ask whether or not the involuntary capture of attention by a
      specific information type can produce domain-specific activation. Participants
      indicated the presence of a flicker in rapidly alternating letter-string masks
      presented in the periphery. Despite letters not being relevant to the task, we
      found, using functional MRI and a novel task that allowed us to contrast attended
      and unattended processing of the same visual information, a robust modulation by
      attentional capture in a localized letter-processing region. This finding
      suggests that the involuntary capture of attention is sufficient to produce
      domain-specific activation in early visual processing.

PMID- 17558281
TI  - Olfactory enrichment enhances the survival of newly born cortical neurons in
      adult mice.
AB  - Neurogenesis persists in the adult rodent olfactory epithelium and olfactory
      bulbs. Recent studies suggest that neurogenesis might also occur in the adult
      rodent piriform cortex, the primary cortical projection site of the olfactory
      bulbs. To determine whether olfactory enrichment influences neurogenesis in the
      mouse piriform cortex, olfactory enrichment was used in combination with
      bromodeoxyuridine labeling. Quantification of the number of bromodeoxyuridine
      labeled cells in the piriform cortex that double label for either the immature
      neuronal marker, doublecortin, or the mature neuronal marker, neuronal nuclei or
      NeuN, showed that olfactory enrichment increases the survival of newborn neurons
      in the piriform cortex. These results confirm that neurogenesis occurs in the
      piriform cortex of rodents and suggest that it may play a neuroplastic role
      there.

PMID- 17558283
TI  - Heterospecific and conspecific social cognition in the anterior cingulate cortex.
AB  - The development of human social cognition has allowed interactions with other
      species and the formation of a cooperative multi-species society. This feature
      posited keen attention on the following question: is heterospecific social
      cognition represented in the same brain areas as conspecific social cognition?
      Here we investigated brain activity accompanying the facial recognition of
      familiar humans and of companion dogs, both of whom had real social interactions
      with participants. The rostroventral anterior cingulate cortex responded to both
      species whereas the caudal anterior cingulate cortex was sensitive only to
      familiar humans. Social cognition processes may be dual-layered: the
      rostroventral anterior cingulate cortex is associated with fundamental and
      intuitive aspects, whereas the caudal anterior cingulate cortex is concerned with
      the analysis of complex social interactions.

PMID- 17558282
TI  - Increased amygdala activation to neutral faces is associated with better face
      memory performance.
AB  - Recent evidence suggests that the role of the amygdala may extend beyond threat
      detection to include processing socially relevant stimuli in general. Thus, we
      investigated perception and memory for neutral faces; a stimulus-type that lacks
      emotional valence yet contains relevant social information. Participants viewed
      neutral faces or houses when undergoing functional MRI. Neutral face memory
      testing was conducted outside the scanner. In the functional MRI of faces vs.
      houses contrast, significant bilateral activation in the amygdala and lateral
      fusiform gyrus was observed. Increased bilateral amygdala activation was
      associated with better delayed-memory performance. These findings indicate that
      the role of the amygdala may include processing neutral yet socially relevant
      stimuli. Further, amygdala activation, independent of emotional valence, appears
      to be associated with memory enhancement.

PMID- 17558284
TI  - Temporal course of vibrotactile imagery.
AB  - This study examined the temporal courses of imagery processes by having
      participants imagining vibrotactile sensation as if perceived by the right-hand
      second finger. The results indicate that the imagery condition elicited a less
      negative going N400 and then a less positive going P600 than the control
      condition (perceived without imagining). This is suggestive of a sequential
      process of retrieving experiences from memory, generating images, and then
      maintaining the images. Dipole analysis further supports that N400 and P600 (or
      long latency P300) can be respectively regarded as part of the generic 'imagery
      network' and as modality-specific processes of imagery.

PMID- 17558285
TI  - NPY mediates basal and seizure-induced proliferation in the subcallosal zone.
AB  - Stem cell niches exist around the lateral ventricle and in the subgranular layer
      of the dentate gyrus, supporting adult neurogenesis. Recently, a third germinal
      layer, the subcallosal zone has been identified supporting the generation of
      oligodendrocytes in the adult brain. We have previously described a proliferative
      role for neuropeptide Y on precursors in the dentate gyrus, caudal subventricular
      zone and subcallosal zone under basal conditions and in the dentate gyrus after
      seizures. Here we sought to determine a role for neuropeptide Y in seizure
      induced proliferation in the subcallosal niche. Using the chemoconvulsant kainate
      and neuropeptide Y(-/-) mice with controls, we show an effect of neuropeptide Y
      on basal proliferation and demonstrate a significant reduction in seizure-induced
      proliferation in the subcallosal zone.

PMID- 17558286
TI  - Bridging the gap between the semantic N400 and the early old/new memory effect.
AB  - We set out to investigate the extent to which semantic integration processes
      during language comprehension indexed by the N400 component affect subsequent
      declarative memory processes as revealed by the putative event-related potential
      correlates of familiarity and recollection. To this end we designed an incidental
      recognition memory test whose study material was composed of sentences that were
      either correct or contained a semantic or syntactic violation. By this means it
      was possible to examine the mnemonic consequences of the N400 amplitude at study.
      We found a significant correlation between the amplitude of the N400 at encoding
      and the magnitude of the familiarity-related early old/new effect at test. It is
      argued that the processes that contributed to N400 generation increase the
      likelihood of familiarity-based recognition memory.

PMID- 17558287
TI  - Microsaccades distinguish between global and local visual processing.
AB  - Much is known about the functional mechanisms involved in visual search. Yet, the
      fundamental question of whether the visual system can perform different types of
      visual analysis at different spatial resolutions still remains unsettled. In the
      visual-attention literature, the distinction between different spatial scales of
      visual processing corresponds to the distinction between distributed and focused
      attention. Some authors have argued that singleton detection can be performed in
      distributed attention, whereas others suggest that even such a simple visual
      operation involves focused attention. Here we showed that microsaccades were
      spatially biased during singleton discrimination but not during singleton
      detection. The results provide support to the hypothesis that some coarse visual
      analysis can be performed in a distributed attention mode.

PMID- 17558288
TI  - Therapeutic time window and effect of intracarotid neural stem cells
      transplantation for intracerebral hemorrhage.
AB  - This study investigated the therapeutic effect of neural stem cells transplanted
      via the carotid artery at different times after intracerebral hemorrhage. A great
      number of 5-bromo-2-deoxyuridine-positive cells were observed surviving and
      distributed evenly in the perihematoma areas. Phenotypes of grafted cells
      depended upon time of transplantation, and the later the cells were transplanted,
      the larger the percentage of cells that differentiated into neurons. Animals
      treated at 7 and 14 days after injury exhibited the most significant improvements
      in behavioral tests. Therefore,intracarotid injection allows efficient delivery
      of cells to the injured hemisphere, especially during the period 7-14 days after
      injury, and may potentially be applicable in humans.

PMID- 17558290
TI  - Event-related potential N270 correlates of brand extension.
AB  - The aim of this study is to investigate the neural mechanism of extending a brand
      in a specific product category to other product categories. Facing two sequential
      stimuli in pairs consisting of beverage brand names (stimulus 1) and product
      names (stimulus 2) in other categories, 16 participants were asked to indicate
      the suitability of extending the brand in stimulus 1 to the product category in
      stimulus 2. These stimulus pairs were divided into four conditions depending on
      the product category in stimulus 2: beverage, snack, clothing, and household
      appliance. A negative component, N270, was recorded for each condition on the
      participants' scalps,whereas the maximum amplitude was observed at the frontal
      area. Greater N270 amplitude was observed when participants were presented with
      stronger conflict between the brand product category (stimulus 1) and the
      extension category (stimulus 2). It suggests that N270 can be evoked not only by
      a conflict of physical attributes (different shapes of words of brand and product
      names) but also by that of lexical content. From the marketing perspective, N270
      can be potentially used as a reference measure in brand-extension attempts.

PMID- 17558289
TI  - Corelease of GABA/glycine in lamina-X of the spinal cord of neonatal rats.
AB  - Spinal-cord slices from neonatal rats were used to record lamina-X neurons using
      the patch-clamp technique under whole cell recording configuration. Lamina-X
      surrounds the central canal of the spinal cord and contains sympathetic
      preganglionic neurons of the central autonomic nucleus. Miniature inhibitory
      postsynaptic currents were recorded in the presence of tetrodotoxin and kynurenic
      acid to block action potential-dependent transmitter release and glutamatergic
      transmissions, respectively. We recorded mixed gamma-amino-n-butyric acid/glycine
      miniature synaptic currents suggesting that gamma-amino-n-butyric acid and
      glycine can be coreleased from the same single synaptic vesicles, and that this
      corelease can be detected by the postsynaptic cell. In addition, acetylcholine
      can induce the release of gamma-amino-n-butyric acid/glycine by acting
      presynaptically at nicotinic receptors located on the gamma-amino-n-butyric acid
      ergic/glycinergic terminals.

PMID- 17558291
TI  - Role of the medial temporal lobe in time estimation in the range of minutes.
AB  - This study examined the role of medial temporal lobe structures in verbal
      estimation and production of time intervals. Left medial temporal lobe lesions
      produced deficits in both tasks, whereas right medial temporal lobe lesions only
      disturbed time production. Although both tasks require adequate use of
      chronometric units, they seem to be subserved by distinct cognitive processing
      and to depend on different neural substrates. Verbal estimation of intervals in
      retrospect seems to depend mainly on contextual memory, and production of
      intervals depends more specifically on the mental load devoted to time. These
      findings, documenting for the first time the role of each temporal lobe in
      duration estimation within the range of minutes, are discussed in light of memory
      based and attentional models of time.

PMID- 17558292
TI  - Isolated Flinders Sensitive Line rats have decreased dopamine D2 receptor mRNA.
AB  - Social isolation has profound effects on animal behavior and dopamine systems. We
      investigated the effect of social isolation on the dopamine receptor and
      neuropeptide mRNAs in the brain reward system in an animal model of depression,
      the Flinders Sensitive Line rats and Sprague-Dawley controls. We demonstrate that
      socially isolated but not group housed Flinders sensitive line rats had lower
      dopamine D2 receptor mRNA levels compared with Sprague-Dawley rats. Isolated and
      group housed Flinders Sensitive Line rats had higher levels of dopamine D1
      receptor and substance P and enkephalin but not dynorphin mRNAs when compared
      with Sprague-Dawley rats. Our findings of decreased dopamine D2 receptor levels
      in socially isolated Flinders Sensitive Line rats suggest that low D2 receptor
      expression may play a role in pathophysiology of depression.

PMID- 17558293
TI  - Hypoxic remodelling of Ca2+signalling in SH-SY5Y cells: influence of glutathione.
AB  - Prolonged hypoxia alters various cellular processes, including Ca2+ signalling.
      As these effects can be prevented by antioxidants, we examined the role of
      glutathione, the major intracellular redox buffer, in modulation of Ca2+
      signalling in the human neuroblastoma SH-SY5Y by hypoxia. Rises of [Ca2+]i evoked
      by bradykinin, and subsequent capacitative Ca2+ entry, were enhanced by prior
      hypoxia (1% O2, 24 h) without effect on reduced glutathione levels. Glutathione
      depletion reversed the effects of chronic hypoxia, but did not affect
      normoxically cultured cells. Elevation of glutathione levels also prevented the
      effects of hypoxia, but restored such effects in glutathione-depleted cells.
      Glutathione is therefore required for hypoxia to modify Ca2+ signalling, but its
      role is more complex than simple buffering of reactive oxygen species.

PMID- 17558294
TI  - 14-3-3 proteins and protein phosphatases are not reduced in tau-deficient mice.
AB  - Tau is an axonal microtubule-associated protein, whose dysfunction causes
      neurodegenerative diseases such as Alzheimer's disease and other tauopathies.
      Earlier studies have shown the interactions of tau with glycogen synthase kinase
      3beta, 14-3-3zeta, protein phosphatase 1 and protein phosphatase 2A. In this
      study, we compared the amounts of these tau-interacting proteins in brain
      microtubule-enriched fractions from wild-type and tau-deficient mice. Contrary to
      our expectation, we detected no difference in the amount of these proteins
      between wild-type and tau-deficient mice. Our findings indicate that only a small
      portion of tau-interacting proteins are bound to tau in vivo, and suggest the
      existence of other scaffolding proteins. We propose that tau-deficient mice are
      an ideal system for confirming the function of tau-interacting proteins.

PMID- 17558295
TI  - The use of the geomagnetic field for short distance orientation in zebra finches.
AB  - Although the ability to use the Earth's magnetic field for long distance
      orientation and navigation has been demonstrated in many animals, the search for
      the appropriate receptor has not yet finished. It is also not entirely clear
      whether the use of magnetic field information is restricted to specialists like
      migrating birds, or whether it is a sense that is also suited to short distance
      orientation by avian species. We successfully trained nonmigratory zebra finches
      in a four-choice food-search task to use the natural magnetic field as well as an
      experimentally shifted field for short distance orientation, supporting the view
      that magnetic field perception may be a sense existing in all bird species. By
      using a conditioning technique in a standard laboratory animal, our experiments
      will provide an ideal basis for the search for the physiological mechanisms of
      magnetic field perception.

PMID- 17558296
TI  - Methylphenidate improves cue navigation in the Morris water maze in rats.
AB  - Despite its still rapidly increasing use in the treatment of the attention
      deficit/hyperactivity disorder, the effects of methylphenidate on behavior and
      learning are not yet fully understood. We have used the Morris water maze to
      study effects of methylphenidate (1 mg/kg) on target-oriented behavior and
      visuospatial learning in young rats. Although the relatively low dose of 1 mg/kg
      methylphenidate changed the behavior in the Morris water maze when the goal was
      visible, reducing times to reach the visible platform, learning of the position
      of the hidden platform, was not influenced, nor was 'relearning' after shifting
      the position of the platform. These results indicate that methylphenidate can
      influence goal-oriented behavior at doses that do not change visuospatial
      learning.

PMID- 17558297
TI  - Practice and perfect: length of training and structural brain changes in
      experienced typists.
AB  - Motor training results in performance improvement. It is not yet fully understood
      the extent to which functional improvement is reflected in changes in brain
      structure. To investigate the presence and degree of structural brain plasticity
      induced by long-term bimanual motor activity, we studied 17 right-handed
      professional typists with average duration of typing practice of 11 years. Using
      optimized voxel-based morphometry, we correlated the duration of practice and
      grey matter volume. Regions of interest were applied using 116 previously
      segmented predefined brain sites. We found a significant positive regression
      between grey matter volume and duration of practice in brain regions related to
      the programming of motor tasks. Long-term bimanual training may increase grey
      matter volume in the brains of professional typists.

PMID- 17558298
TI  - Perceptual processing time differences owing to visual field asymmetries.
AB  - Recent experiments have reported increased endpoint accuracy for movements
      performed in the lower vs. the upper visual field, suggesting that there is
      superior feedback-based processing in the lower visual field owing to a
      visuomotor subsystem processing advantage. Differences, however, in the
      perceptual subsystem may also play a role in the lower visual field advantage. In
      this study, participants performed an inspection time task, a measure of
      perceptual processing time, requiring the identification of an asymmetrical 'pi'
      stimulus presented in the central, upper, or the lower visual field for a brief
      period. Significant differences between the percentage of correct identifications
      between visual fields indicated a lower visual field advantage over upper visual
      field for perceptual identification.

PMID- 17558299
TI  - Laterality and aging of thalamic subregions measured by diffusion tensor imaging.
AB  - Thalamic nuclei are comprised of fibers connecting associated cortical regions,
      and abnormalities of the thalamus are correlated with abnormalities in cognition
      and behavior. Some previous studies showed the laterality of the whole thalamus
      and the regional differences among thalamic nuclei. This led us to assess
      regional characteristics in five major subregions of both sides of the thalamus
      using diffusion-tensor imaging. Statistically significant lateralities and
      regional differences were found among the thalamic subregions. Age has a
      significant correlation with diffusion-tensor imaging metrics where their
      projection areas are thought to be vulnerable to normal aging. Our results
      confirmed that the thalamic subregions behave independently, and their respective
      microstructures warrant further investigations.

PMID- 17558300
TI  - Age-related multisensory enhancement in a simple audiovisual detection task.
AB  - Older adults are known to gain more than younger adults from the simultaneous
      presentation of semantically congruent sensory stimuli. Although these findings
      are quite exciting, they may not solely be due to age-related differences in
      multisensory processing. Rather, enhanced integration may be explained by
      alterations associated with general cognitive slowing. This study utilized a task
      that eliminated most high-order cognitive processing. As such, no significant
      differences in unisensory response times were seen; however, older adults
      actually showed faster multisensory responses than younger adults. Older adults
      continued to show significantly greater multisensory enhancement than younger
      adults. Data support the conclusion that differences in multisensory processing
      for older adults cannot be explained solely by the effects of general cognitive
      slowing.

PMID- 17558301
TI  - Inverse correlation between amyloid precursor protein and synaptic plasticity in
      transgenic mice.
AB  - Soluble amyloid beta peptide (Abeta) is believed to cause synaptic dysfunction in
      the early stages of Alzheimer's disease. Here, we examined in-vivo synaptic
      functions in the hippocampus in two lines of transgenic mice expressing different
      amounts of human wild-type amyloid precursor protein (APP). Compared with
      nontransgenic littermates, one transgenic line with higher APP expression
      displayed potent inhibition of paired-pulse facilitation and long-term
      potentiation in the absence of amyloid deposition, whereas the line with lower
      APP expression exhibited moderate inhibition of paired-pulse facilitation and
      long-term potentiation. Soluble Abeta1-42 levels in their brains nearly
      paralleled APP levels. The observed inverse correlation between APP expression
      and synaptic plasticity appears to support the current hypothesis regarding the
      pathogenic roles of soluble Abeta.

PMID- 17558302
TI  - CYP2C8 haplotype structures and their influence on pharmacokinetics of paclitaxel
      in a Japanese population.
AB  - OBJECTIVE: CYP2C8 is known to metabolize various drugs including an anticancer
      drug paclitaxel. Although large interindividual differences in CYP2C8 enzymatic
      activity and several nonsynonymous variations were reported, neither haplotype
      structures nor their associations with pharmacokinetic parameters of paclitaxel
      were reported. METHODS: Haplotype structures of the CYP2C8 gene were inferred by
      an expectation-maximization based program using 40 genetic variations detected in
      437 Japanese patients, which included cancer patients. Associations of the
      haplotypes and paclitaxel pharmacokinetic parameters were analyzed for 199
      paclitaxel-administered cancer patients. RESULTS: Relatively strong linkage
      disequilibriums were observed throughout the CYP2C8 gene. We estimated 40
      haplotypes without an amino-acid change and nine haplotypes with amino acid
      changes. The 40 haplotypes were classified into six groups based on network
      analysis. The patients with heterozygous *IG group haplotypes harboring several
      intronic variations showed a 2.5-fold higher median area under concentration-time
      curve of C3'-p-hydroxy-paclitaxel and a 1.6-fold higher median value of C3'-p
      hydroxy-paclitaxel/paclitaxel area under concentration-time curve ratio than
      patients bearing no *IG group haplotypes (P<0.001 for both comparisons by Mann
      Whitney U-test). No statistically significant differences, however, were observed
      between patients with and without the *IG group (haplotypes) in clearance and
      area under concentration-time curve of paclitaxel, area under concentration-time
      curve of 6alpha-hydroxy-paclitaxel and 6alpha-, C3'-p-dihydroxy-paclitaxel, and
      area under concentration-time curve ratio of 6alpha-hydroxy
      paclitaxel/paclitaxel. CONCLUSION: CYP2C8*IG group haplotypes were associated
      with increased area under concentration-time curve of C3'-p-hydroxy-paclitaxel
      and area under concentration-time curve ratio of C3'-p-hydroxy
      paclitaxel/paclitaxel. Thus, *IG group haplotypes might be associated with
      reduced CYP2C8 activity, possibly through its reduced protein levels.

PMID- 17558303
TI  - The risk of myocardial infarction in patients with reduced activity of cytochrome
      P450 2C9.
AB  - OBJECTIVE: The aim of the present follow-up study was to investigate whether the
      enzyme activity of the human cytochrome P450 (CYP) 2C9 isoenzyme is associated
      with myocardial infarction. METHODS: We investigated whether the variant alleles
      CYP2C9*2 and CYP2C9*3 or the use of CYP2C9 substrates or inhibitors was
      associated with an increased risk of myocardial infarction in 2210 men and 3534
      women from the Rotterdam Study, a prospective population-based cohort study of
      individuals aged 55 years or older. RESULTS: In women, the use of CYP2C9
      substrates or inhibitors was significantly associated with incident myocardial
      infarction with a hazard ratio of 2.48 (95% confidence interval: 1.55-3.96).
      Within the group of female carriers of a variant allele, the use of CYP2C9
      substrates or inhibitors was associated with a fourfold increased risk of
      myocardial infarction (hazard ratio 3.86, 95% confidence interval: 1.93-7.75), as
      compared with non-use. Neither the use of CYP2C9 inhibitors or substrates nor the
      variant CYP2C9 alleles were associated with an increased risk of myocardial
      infarction in men. CONCLUSIONS: Drugs that are metabolized by CYP2C9 increase the
      risk of myocardial infarction in women. This risk was even higher in women with
      allelic variants of CYP2C9 with reduced enzyme activity.

PMID- 17558304
TI  - A pharmacogenomics study of the human estrogen glucuronosyltransferase UGT1A3.
AB  - UGT1A3 is one of the most efficient at conjugating estrone, a precursor for
      biosynthesis of estradiol in peripheral tissues. We established the genetic
      mechanisms that might contribute to individual variation in UGT1A3 expression and
      activity. UGT1A3 first exon and 5'-flanking regions were sequenced in 249
      Caucasians. We identified 17 polymorphisms, among them seven regulatory and 10
      exonic polymorphisms with six leading to amino-acid changes. Luciferase reporter
      assays, site-directed mutagenesis and electrophoretic mobility shift assays using
      hepatoma HepG2 cells were carried out to show functionality of variant promoters.
      Reduced transcriptional activity was associated with all six variant promoters
      (two-fold; P<0.001). One of the potential mechanisms would involve the -148 T>C
      and -581 C>T variations that modulate gene function by affecting hepatocyte
      nuclear factor-1alpha and hepatocyte nuclear factor-4alpha binding, respectively.
      Then, estrone-conjugating activity was assessed with 11 heterologously expressed
      allozymes. Three phenotypes were observed; UGT1A3*1, *2 (WR, VA) and *3 (WR) with
      high intrinsic clearance values; UGT1A3*5 (QR, WR), *7 (FI), *9 (WR, ML), *10
      (VA) and *11 (WR, VA and MI) had intermediate CLint (2X-10X lower vs. *1),
      whereas UGT1A3*4 (RW), *6 (WR, VA, MV) and *8 (AV) had low CLint (>10X lower vs.
      *1). Diplotype analyses indicate that 20.1% of individuals carry two alleles
      affecting UGT1A3 expression and/or activity. This study did not investigate
      genotype-phenotype association, but raise the possibility that genetically
      determined variation might contribute to variability in the inactivation of
      estrone by UGT1A3 and subsequent changes in lifetime exposure to estrogens
      potentially modifying risk of cancer.

PMID- 17558305
TI  - Irinotecan pharmacokinetics/pharmacodynamics and UGT1A genetic polymorphisms in
      Japanese: roles of UGT1A1*6 and *28.
AB  - OBJECTIVES: SN-38, an active metabolite of irinotecan, is detoxified by
      glucuronidation with UGT1A isoforms, 1A1, 1A7, 1A9, and 1A10. The pharmacogenetic
      information on UGT1A haplotypes covering all these isoforms is important for the
      individualized therapy of irinotecan. Associations between UGT1A haplotypes and
      pharmacokinetics/pharmacodynamics of irinotecan were investigated to identify
      pharmacogenetic markers. METHODS: Associations between UGT1A haplotypes and the
      area under concentration curve ratio (SN-38 glucuronide/SN-38) or toxicities were
      analyzed in 177 Japanese cancer patients treated with irinotecan as a single
      agent or in combination chemotherapy. For association analysis, diplotypes of
      UGT1A gene segments [(1A1, 1A7, 1A9, 1A10), and Block C (common exons 2-5)] and
      combinatorial haplotypes (1A9-1A7-1A1) were used. The relationship between
      diplotypes and toxicities was investigated in 55 patients treated with irinotecan
      as a single agent. RESULTS: Among diplotypes of UGT1A genes, patients with the
      haplotypes harboring UGT1A1*6 or *28 had significantly reduced area under
      concentration curve ratios, with the effects of UGT1A1*6 or *28 being of a
      similar scale. A gene dose effect on the area under concentration curve ratio was
      observed for the number of haplotypes containing *28 or *6 (5.55, 3.62, and 2.07
      for 0, 1, and 2 haplotypes, respectively, P<0.0001). In multivariate analysis,
      the homozygotes and double heterozygotes of *6 and *28 (*6/*6, *28/*28 and
      *6/*28) were significantly associated with severe neutropenia in 53 patients who
      received irinotecan monotherapy. CONCLUSIONS: The haplotypes significantly
      associated with reduced area under concentration curve ratios and neutropenia
      contained UGT1A1*6 or *28, and both of them should be genotyped before irinotecan
      is given to Japanese and probably other Asian patients.

PMID- 17558306
TI  - Genetic polymorphisms in the amino acid transporters LAT1 and LAT2 in relation to
      the pharmacokinetics and side effects of melphalan.
AB  - OBJECTIVES: Melphalan is widely used in the treatment of multiple myeloma.
      Pharmacokinetics of this alkylating drug shows high inter-individual variability.
      As melphalan is a phenylalanine derivative, the pharmacokinetic variability may
      be determined by genetic polymorphisms in the L-type amino acid transporters LAT1
      (SLC7A5) and LAT2 (SLC7A8). METHODS: Pharmacokinetics were analysed in 64
      patients after first administration of intravenous melphalan. Severity of side
      effects was documented according to WHO criteria. Genomic DNA was analysed for
      polymorphisms in LAT1 and LAT2 by sequencing of the entire coding region, intron
      exon boundaries and 2 kb upstream promoter region. Selected polymorphisms in the
      common heavy chain of both transporters, the protein 4F2hc (SLC3A2), were
      analysed by single nucleotide primer extension. RESULTS: Melphalan
      pharmacokinetics was highly variable with up to 6.2-fold differences in total
      clearance. A total of 44 polymorphisms were identified in LAT1 and 21
      polymorphisms in LAT2. From all variants, only five were in the coding region and
      only one heterozygous non-synonymous polymorphism (Ala94Thr) was found in LAT2.
      Numerous polymorphisms were found in the LAT1 and LAT2 5'-flanking regions but
      did not correlate with expression of the respective genes. No significant
      correlations could be observed between the polymorphisms in 4F2hc, LAT1, and LAT2
      with melphalan pharmacokinetics or with melphalan side effects. CONCLUSIONS: The
      study confirmed that these transporter genes are highly conserved, particularly
      in the coding sequences. Genetic variation in 4F2hc, LAT1, and LAT2 does not
      appear to be a major cause of inter-individual variability in pharmacokinetics
      and of adverse reactions to melphalan.

PMID- 17558307
TI  - Association of the RGS2 gene with extrapyramidal symptoms induced by treatment
      with antipsychotic medication.
AB  - OBJECTIVES: To investigate the role of genes encoding regulators of G protein
      signaling in early therapeutic response to antipsychotic drugs and in
      susceptibility to drug-induced extrapyramidal symptoms. As regulators of G
      protein signaling and regulators of G protein signaling-like proteins play a
      pivotal role in dopamine receptor signaling, genetically based, functional
      variation could contribute to interindividual variability in therapeutic and
      adverse effects. METHODS: Consecutively hospitalized, psychotic patients with
      Diagnostic and Statistical Manual of Mental Disorder-IV schizophrenia (n=121)
      were included in the study if they received treatment with typical antipsychotic
      medication (n=72) or typical antipsychotic drugs and risperidone (n=49) for at
      least 2 weeks. Clinical state and adverse effects were rated at baseline and
      after 2 weeks. Twenty-four single nucleotide polymorphisms were genotyped in five
      regulators of G protein signaling genes. RESULTS: None of the single nucleotide
      polymorphisms were related to clinical response to antipsychotic treatment at 2
      weeks. Five out of six single nucleotide polymorphisms within or flanking the
      RGS2 gene were nominally associated with development or worsening of parkinsonian
      symptoms (PARK+) as measured by the Simpson Angus Scale, one of them after
      correction for multiple testing (rs4606, P=0.002). A GCCTG haplotype encompassing
      tagging single nucleotide polymorphisms within and flanking RGS2 was
      significantly overrepresented among PARK+ compared with PARK--patients (0.23 vs.
      0.08, P=0.003). A second, 'protective', GTGCA haplotype was significantly
      overrepresented in PARK--patients (0.13 vs. 0.30, P=0.009). Both haplotype
      associations survive correction for multiple testing. CONCLUSIONS: Subject to
      replication, these findings suggest that genetic variation in the RGS2 gene is
      associated with susceptibility to extrapyramidal symptoms induced by
      antipsychotic drugs.

PMID- 17558308
TI  - Polymorphism of the DNA repair enzyme XRCC1 is associated with treatment
      prediction in anthracycline and cyclophosphamide/methotrexate/5-fluorouracil
      based chemotherapy of patients with primary invasive breast cancer.
AB  - OBJECTIVES: Outcome and survival in anthracycline-based and
      cyclophosphamide/methotrexate/5-fluorouracil-based chemotherapy of invasive
      breast cancer are unpredictable. Insights into treatment prediction are expected
      from studies searching for an association between genetic polymorphisms and
      treatment outcome effects. A common feature of treatment with chemoreagents is
      therapeutically induced DNA damage. Therefore, we tested the hypothesis of a
      relationship between event-free survival and genotype distributions of seven
      polymorphic DNA repair enzymes and four cell cycle regulators. BASIC METHODS:
      This case-case comparison included 180 patients with primary invasive breast
      cancer diagnosed between 1986 and 2000 and subjected to adjuvant chemotherapy
      (anthracycline/cyclophosphamide or cyclophosphamide/methotrexate/5-fluorouracil).
      Ninety-two patients were reported without recurrence and 88 were reported with
      recurrences or dead. Median clinical follow-up was 61.7 months. Constitutional
      DNA isolated from archived tissues was genotyped at 19 loci by matrix-assisted
      laser desorption/ionization time-of-flight mass spectrometry. Statistical
      analyses included adjusted risk estimates, Kaplan-Meier analyses, Cox
      proportional hazard model, and permutation testing. MAIN RESULTS: Carriers of the
      XRCC1_1196_AA genotype had a reduced risk for recurrence/death (odds ratio
      adjusted 0.19; 95% confidence interval: 0.06-0.61), which was observed in
      survival analyses of all patients (P=0.003) and patients treated with
      chemotherapy but not radiotherapy (P=0.006). Multivariate analysis confirmed
      XRCC1 as a potential treatment predictor (hazard ratio 0.62; 95% confidence
      interval: 0.43-0.89). The result was stable upon permutation testing. No other
      significant associations were observed. CONCLUSION: The DNA repair enzyme XRCC1
      is a potential treatment predictor for the outcome and survival of anthracycline
      and cyclophosphamide/methotrexate/5-fluorouracil-based chemotherapy of invasive
      breast cancer.

PMID- 17558309
TI  - A functional G300S variant of the cysteinyl leukotriene 1 receptor is associated
      with atopy in a Tristan da Cunha isolate.
AB  - Atopy is a well-defined immune phenotype that is reported to be a risk factor for
      asthma. Among the many loci that contribute to a genetic predisposition to
      asthma, the cysteinyl leukotriene receptor genes and their variants have been
      important subjects of study because they are functionally and pharmacologically
      implicated in the atopy phenotype affecting many asthma subjects. Moreover, the
      product of cysteinyl-leukotriene 1 receptor gene (CysLT1), located at Xq13.2, is
      targeted by LT receptor antagonists. In our earlier association study, the M201V
      variant of the cysteinyl-leukotriene 2 receptor gene (CysLT2), located at 13q14,
      was implicated in atopic asthma. Here we report the screening of the coding
      region of the CysLT1, gene in the highly asthmatic Tristan da Cunha population.
      In this population, we discovered a CysLT1 G300S variant that is carried with a
      significantly higher frequency in atopics and asthmatics from the Tristan da
      Cunha population. Furthermore, we report the asthma independent association of
      the CysLT1 G300S variant with atopy. Subsequently, we compared the changes
      conferred by each SNP on CysLT function. The CysLT1 300S receptor interacts with
      LTD4 with significantly greater potency. For the 300S variant, a statistically
      significant decrease in the effector concentration for half-maximum response
      (EC50) for intracellular Ca flux and total InsP generation is observed. Other
      aspects of the receptor function and activity, such as desensitization,
      pharmacologic profile in response to montelukast, and cellular localization, are
      unchanged. These in vitro analyses provide evidence that the 300S CysLT1 variant,
      found more commonly in atopics in the Tristan da Cunha population, encodes a
      functionally more sensitive variant.

PMID- 17558310
TI  - The 1976C>T polymorphism in the adenosine A2A receptor gene does not affect the
      vasodilator response to adenosine in humans in vivo.
AB  - The 1976C>T polymorphism in the adenosine A2A receptor gene (ADORA2A) modulates
      the psychological response to administration of the adenosine receptor antagonist
      caffeine. We quantified the vascular response to adenosine and caffeine to
      determine the relevance of this variant allele in the physiological response to
      these agents. We selected 10 study participants with the TT genotype and 10 CC
      controls, matched for activities of other proteins involved in the metabolism of
      adenosine. The vasodilator response to the intrabrachial administration of
      adenosine (0.5, 1.5, 5.0, 15.0, and 50.0 microg/min/dl; venous occlusion
      plethysmography) was not different between the groups (P=0.4). In addition, the
      effect of subsequent administration of caffeine (90 microg/min/dl) was not
      different (P=0.7). We conclude that the 1976C>T polymorphism does not affect the
      vascular response to adenosine and caffeine in humans in vivo. Therefore, this
      polymorphism does not contribute to the variation in the effects of adenosine
      receptor stimulation.

PMID- 17558311
TI  - Single nucleotide polymorphisms in the P2X7 gene are associated to fracture risk
      and to effect of estrogen treatment.
AB  - OBJECTIVES: The purinergic P2RX7 receptor (P2RX7) has been shown to play a role
      in the regulation of osteoblast and osteoclast activity. The aim of this study
      was to determine the presence of polymorphisms in exon 13 of the P2X7 gene and
      the association with osteoclast apoptosis in vitro and bone status in vivo.
      METHODS: A total of 1764 postmenopausal women were genotyped for three single
      nucleotide polymorphisms detected after sequencing of exon 13 of P2X7. Bone
      markers, bone mineral density of the hip and lumbar spine were determined at
      baseline and after 10 years, and vertebral fracture incidence after 10 years. In
      vitro ATP-induced caspase-1 determinations were performed on osteoclasts from the
      different genotypes. RESULTS: Three polymorphisms were detected (Gln460Arg,
      Glu496Ala, and Ile568Asn). None of the polymorphisms was related to bone mineral
      density or changes in bone mineral density over 10 years in hormone replacement
      therapy naive women. The Ile568Asn polymorphism was however, associated with
      effect of hormone replacement therapy. Furthermore, the 10-year fracture
      incidence was significantly associated with both the Glu496Ala and the Ile568Asn.
      The Glu496Ala polymorphism was closely related to ATP-induced osteoclast
      apoptosis in vitro, as osteoclasts from individuals homozygous for the C allele
      had significantly decreased apoptotic activity. CONCLUSION: The P2X7 Glu496Ala
      and the Ile568Asn single nucleotide polymorphisms are associated with 10-year
      fracture risk in postmenopausal women and response to hormone replacement therapy
      treatment. Further, the Glu496Ala polymorphism is strongly influencing osteoclast
      apoptosis in vitro, which could contribute to increased fracture risk.

PMID- 17558312
TI  - Tears of the retinal pigment epithelium: an old problem in a new era.
AB  - BACKGROUND/PURPOSE: Recent attention has focused upon several reports of retinal
      pigment epithelium (RPE) tears following vascular endothelial growth factor
      (VEGF)-modulating therapy. The authors review the clinical features, etiologies,
      imaging characteristics, and pathogenesis of RPE tears and their relationship
      with intravitreal anti-VEGF treatments. METHODS: The authors conducted a
      comprehensive literature search of RPE tears or rips of any etiology using the
      PubMed database. They have also included a retrospective analysis of an
      additional five cases of RPE tears following anti-VEGF therapy, four after
      bevacizumab and one after ranibizumab. RESULTS: Thirty-three cases of RPE tear
      after treatment with pegaptanib, bevacizumab, or ranibizumab have been previously
      reported in the literature. The authors have collected and analyzed the clinical
      features for 25 of these cases for which this information was available. The
      authors have also included analysis of an additional five cases. Common features
      of each of these 30 cases included advanced age of the patient, the presence of
      fibrovascular pigment epithelial detachment (PED) or PED associated with
      choroidal neovascularization (CNV), and diagnosis of the tear within 4 to 8 weeks
      of the first or second injection. CONCLUSIONS: RPE tears may develop during the
      course of anti-VEGF therapy for age-related macular degeneration-related PED.
      Patients with high-risk lesions, especially large irregular PED associated with
      CNV, should be counseled and monitored for this complication, which may limit
      visual prognosis.

PMID- 17558313
TI  - Retinal pigment epithelium tears after intravitreal injection of bevacizumab
      (avastin) for neovascular age-related macular degeneration.
AB  - BACKGROUND: Intravitreal bevacizumab (Avastin, Genentech, Inc., South San
      Francisco, CA) treatment of neovascular age-related macular degeneration (AMD)
      has become an important part of clinical retinal practice. We describe retinal
      pigment epithelium (RPE) tears that were noted after intravitreal injection of
      bevacizumab. METHODS: In this multimember, retrospective case series, data on
      eyes that developed RPE tears after intravitreal bevacizumab injection were
      collected and analyzed. Previous treatments, type of lesion, time to tear, and
      preinjection and final visual acuities were all compared. The total numbers of
      bevacizumab injections were available from all four institutions and compiled to
      estimate the incidence rate. RESULTS: Four retina centers administered a total of
      1,455 intravitreal 1.25-mg bevacizumab injections for neovascular AMD during the
      9-month study period. Twelve patients presented with RPE tears within 4 days to 8
      weeks of injection (mean +/- SD, 24.3 +/- 15.2 days from injection to tear). In
      each case, the RPE tear was preceded by an RPE detachment, and all had a
      component of serous sub-RPE fluid. On the basis of our collective data, we
      estimate an incidence rate of approximately 0.8%. CONCLUSIONS: RPE tears can
      occur after intravitreal injection of bevacizumab. The low incidence of this
      adverse event should not preclude anti-vascular endothelial growth factor therapy
      counseling for patients with neovascular AMD, but eyes with serous RPE
      detachments appear to be most vulnerable to this adverse event.

PMID- 17558314
TI  - Retinal pigment epithelial tears after intravitreal bevacizumab injection for
      neovascular age-related macular degeneration.
AB  - PURPOSE: To study retinal pigment epithelium (RPE) tears after off-label
      intravitreal bevacizumab (Avastin; Genentech, Inc., South San Francisco, CA)
      injection for neovascular age-related macular degeneration. Eyes with a
      vascularized pigment epithelial detachment (PED) that developed an RPE tear were
      compared with eyes with a vascularized PED but without an RPE tear. METHODS: Nine
      retina specialists across the United States and in Europe participated in this
      retrospective case series. All eyes that received intravitreal bevacizumab
      injection for choroidal neovascularization (CNV) over 12 months (October 2005 to
      September 2006) were included. Eyes without all three confirmed tests
      (fluorescein angiography, fundus photography, and optical coherence tomography)
      were excluded from analysis. Statistical analyses were performed on multiple
      characteristics of eyes with a vascularized PED that did and did not develop an
      RPE tear. RESULTS: Among 2,785 intravitreal bevacizumab injections for 1,064
      eyes, RPE tears were found in 22 eyes in 22 patients (2.2%). A vascularized PED
      was present in 21 of 22 eyes that developed an RPE tear (17.1% of PED eyes; 15,
      100% occult CNV; 6, predominantly occult CNV). Mean interval from bevacizumab
      injections to RPE tears was 37.3 days. Mean follow-up time was 124.9 days. Mean
      subfoveal PED size was larger for eyes with tears than for those without tears
      (13.97 mm vs 9.9 mm, respectively; P = 0.01; odds ratio, 1.09). There was
      substantially smaller mean ratio of CNV size to PED size for eyes with tears than
      for those without tears (27.9% vs 67.6%, respectively; P = 0.005). Mean pre
      bevacizumab injection best-corrected Snellen visual acuity was 20/162, and mean
      post-RPE tear best-corrected visual acuity was 20/160 (P = 0.48). CONCLUSION:
      Large PED size is a predictor for RPE tears, and a small ratio of CNV size to PED
      size (<50%) is more common in eyes with RPE tears. Vision may be preserved
      despite RPE tears.

PMID- 17558315
TI  - Impact of optical coherence tomography on surgical decision making for epiretinal
      membranes and vitreomacular traction.
AB  - PURPOSE: To compare retina surgeons' recommendations for management of epiretinal
      membranes (ERM) and vitreomacular traction (VMT) based on clinical assessment
      alone with management based on clinical evaluation supplemented by optical
      coherence tomography (OCT). METHODS: A prospective, masked clinical case series
      was conducted. Surgeons first performed a complete history and physical
      examination on patients referred with the macular disorders under study without
      the benefit of adjunctive OCT, determined whether ERM, VMT, and/or macular edema
      were present, questionably present, or absent, and made a provisional management
      recommendation. The retina specialists then reviewed the OCT images for the
      presence or absence of ERM, VMT, and/or associated macular edema and reconsidered
      the final management recommendation in light of clinical evaluation combined with
      OCT findings. RESULTS: Eighty-four eyes of 73 patients were examined. ERM was
      identified in 66 (78.6%) of 84 eyes using clinical examination compared with 72
      (85.7%) of 84 eyes using OCT (P = 0.06). VMT was identified in 5 (6%) of 84 eyes
      using clinical examination compared with 18 (21.4%) of 84 eyes using OCT (P <
      0.005). Macular edema was identified in 57 (67.9%) of 84 eyes using clinical
      examination compared with 70 (83.3%) of 84 eyes using OCT (P = 0.003). Surgical
      intervention was recommended in 33 cases: 19 (57.6%) based on the history and
      clinical examination findings without OCT information and an additional 14
      (42.4%) based on the combination of clinical evaluation and OCT findings.
      CONCLUSIONS: OCT is more sensitive than clinical examination in detecting ERM,
      VMT, and associated macular edema. Taken together with careful clinical
      evaluation, OCT findings influenced surgeons to recommend consideration of
      surgery to an additional 14 patients (42.2%) in this series.

PMID- 17558316
TI  - Long-term outcomes of pars plana vitrectomy with internal limiting membrane
      removal in diabetic macular edema.
AB  - PURPOSE: To report the long-term visual results and anatomical outcome as
      assessed by optical coherence tomography (OCT) after pars plana vitrectomy (PPV)
      with removal of the internal limiting membrane (ILM) in diabetic macular edema
      (DME). METHODS: Medical records of 27 eyes of 27 patients who underwent PPV with
      ILM removal for DME attributable to diffuse leakage were reviewed. This
      retrospective study included eyes that underwent PPV with ILM removal at our
      institution with preoperative and postoperative OCT assessment of DME. None of
      the eyes had OCT evidence of anteroposterior vitreomacular traction. Main outcome
      measures were foveal thickness and visual acuity changes. RESULTS: Foveal
      thickness decreased by at least 20% in 22 eyes (81.4%) and increased by at least
      20% in 3 eyes (11.1%) with PPV and ILM removal (mean follow-up +/- SD, 27.6 +/-
      7.2 months; range, 12-38 months). Mean foveal thickness decrease +/- SD was 178
      +/- 164 microm (43.6%), with a mean preoperative foveal thickness +/- SD of 408
      +/- 121 microm compared with a mean postoperative foveal thickness +/- SD of 230
      +/- 74 microm (P < 0.001). Recurrence of DME was observed at postoperative month
      24 in 2 eyes and postoperative month 30 in 1 eye. Visual acuity improved by > or
      =2 lines in 10 eyes (37%) and decreased by > or =2 lines in 3 eyes (11.1%). Mean
      best-corrected logMAR (logarithm of the minimum angle of resolution) visual
      acuity +/- SD was 0.75 +/- 0.35 preoperatively and 0.63 +/- 0.33 postoperatively
      (P = 0.033). CONCLUSION: PPV with ILM removal appears to be effective in reducing
      DME and improving visual acuity, and its effectiveness is maintained in the long
      term. Recurrence of DME may be observed in the late postoperative period.

PMID- 17558317
TI  - Functional and structural measurements for the assessment of internal limiting
      membrane peeling in idiopathic macular pucker.
AB  - OBJECTIVE: To investigate the role of structural and functional measurements in
      the assessment of internal limiting membrane (ILM) peeling for the treatment of
      eyes with macular pucker. METHODS: Ten patients with macular pucker who underwent
      pars plana vitrectomy with ILM peeling were studied prospectively. Visual acuity
      measurement, standard automated achromatic perimetry, multifocal
      electroretinography (mfERG), and optical coherence tomography (OCT) were
      performed before and 3 months after surgery. Four surgical samples obtained from
      similar patients were analyzed with electron microscopy. RESULTS: Three months
      after surgery, mean visual acuity +/- SD was significantly improved from 0.4 +/-
      0.11 logMAR to 0.19 +/- 0.13 logMAR (P < or = 0.002), and mean central retinal
      thickness +/- SD was significantly decreased 428 +/- 73 microm to 326 +/- 34
      microm (P < or = 0.002). The mfERG response amplitudes were slightly decreased in
      eight patients, and five of these patients also had asymptomatic decreases in
      visual field sensitivity. The electron micrographs revealed segments of Muller
      cell footplates on the retinal side of the ILM in all four specimens. CONCLUSION:
      In this study, the use of mfERG, OCT, and standard automated achromatic perimetry
      showed changes in macular function and structure postoperatively. These measures
      of visual function and structure allow for better evaluation of the surgical
      outcome and understanding of the changes that may occur after ILM peeling.

PMID- 17558318
TI  - Trans-luminal nd:YAG laser embolysis for branch retinal artery occlusion.
AB  - PURPOSE: To evaluate the clinical efficacy of transluminal YAG laser embolysis
      (TYE) for patients with severe vision loss secondary to a newly diagnosed branch
      retinal artery occlusion (BRAO) with visible emboli. METHODS: Five eyes of five
      patients with acute, severe vision loss secondary to a branch retinal artery
      occlusion with visible emboli and retinal whitening were prospectively examined,
      enrolled, and underwent visual acuity testing, ophthalmic examination, color
      photography, and fluorescein angiography. Each patient was offered TYE and the
      potential risks of the treatment were explained. Follow-up examinations were
      undertaken post-procedure day 1 and subsequent follow-up depended on the clinical
      course. RESULTS: In our five patients baseline best-corrected visual acuity
      (BCVA) was found to be 5/400, count fingers at 3 feet, count fingers at 5 feet,
      20/800, and 20/200. All five of our patients showed improvement in BCVA 1 day
      after TYE. Fluorescein angiography showed immediate and dramatic restoration in
      flow past the obstructed arteriole in all patients. Patient 2 developed
      subretinal hemorrhage, which after vitrectomy and associated procedures the
      acuity improved to 20/25 at 22 days after the TYE. Final BCVA was 20/30, 20/25,
      20/40, 20/30, and 20/40. CONCLUSION: TYE is a treatment modality to be considered
      in patients with BRAO who present acutely with severe vision loss and a visible
      embolus. The risks of TYE must be weighed against the possibility of severe and
      permanent loss of vision secondary to BRAO.

PMID- 17558319
TI  - Assessment of the role of thrombin activatable fibrinolysis inhibitor in retinal
      vein occlusion.
AB  - PURPOSE: To determine whether elevated levels of thrombin activatable
      fibrinolysis inhibitor (TAFI) may contribute to thrombotic risk for patients with
      retinal vein occlusion (RVO) and to investigate the possible correlations between
      TAFI activity level and other conventional risk factors. METHODS: Ninety patients
      with RVO (cases), except those receiving medication affecting the study
      parameters, those undergoing a surgical procedure within the last week, and those
      with kidney and/or liver failure, were enrolled in the study. The control group
      included similar patients matched for age and sex. After written informed consent
      was obtained, parameters including TAFI activity levels, conventional risk
      factors, results of routine hematological examination, and factor V Leiden and
      prothrombin G20210A mutations were evaluated by analysis of blood samples
      obtained after an 8-hour fast. RESULTS: Although TAFI activity levels were
      slightly elevated in cases (190.5 +/- 43.8) compared with controls (183.9 +/-
      41.8), the difference was not statistically significant (P = 0.36). According to
      evaluation of TAFI activity in subgroups (>200%, 150-200%, and 0-150%), 36.7%
      with central RVO, 40.0% with branch RVO, and 30% of controls were found to have
      TAFI activity of >200% (P = 0.83). TAFI activity levels did not correlate with
      age, sex, demographics, clinical status, and hematological variables. Finally, in
      stepwise regression analysis, TAFIa (carboxypeptidase U) activity was not found
      to be an important risk factor for RVO. CONCLUSION: On the basis of these data,
      TAFI activity was not found to be a new risk factor for either type of RVO.
      However, further larger studies may better identify the exact role of TAFI in the
      pathogenesis of RVO.

PMID- 17558320
TI  - Long-term visual outcomes after vitrectomy for macular edema with foveal
      hemorrhage in branch retinal vein occlusion.
AB  - PURPOSE: To determine the long-term visual outcomes after vitreous surgery for
      macular edema with foveal hemorrhage associated with branch retinal vein
      occlusion (BRVO). METHODS: One hundred twenty eyes of 120 patients underwent pars
      plana vitrectomy with or without internal limiting membrane (ILM) peeling for
      macular edema with foveal hemorrhage due to BRVO with a minimum 12 months of
      follow-up. Simultaneous cataract extraction with intraocular lens implantation
      was performed on 117 phakic eyes. RESULTS: Follow-up after surgery ranged from 12
      months to 129 months (average, 48 months). Visual acuity improved in 71% of cases
      at the 1-year visit. Mean visual acuity significantly increased from 0.24
      (median, 0.3) before surgery to 0.57 (median, 0.7) 1 year after surgery (P <
      0.0001) and 0.66 (median, 0.9) at the final visit (P < 0.0001). There was a
      significant difference between visual acuity at 1 year after surgery and visual
      acuity at the final visit (P < 0.0001). Of 120 patients, 95 (79%) had final
      visual acuity of > or =0.5, and 55 (46%) had final visual acuity of > or =1.0.
      ILM removal did not seem to have significant beneficial effects on visual
      outcomes in this series. No serious complications occurred during the follow-up
      period. CONCLUSION: After vitreous surgery for macular edema with foveal
      hemorrhage associated with BRVO, visual acuity continued to improve beyond 1 year
      after surgery. A randomized, multicenter clinical trial is warranted to determine
      the efficacy of this procedure.

PMID- 17558321
TI  - Tomographic features of branching vascular networks in polypoidal choroidal
      vasculopathy.
AB  - PURPOSE: To identify the tomographic features of the branching vascular networks
      in patients with polypoidal choroidal vasculopathy (PCV). METHODS: We
      prospectively performed third-generation optical coherence tomography (OCT) and
      fluorescein angiography for 44 eyes of 42 patients (mean age +/- SD, 67.1 +/- 9.1
      years) with PCV. All eyes had branching vascular networks and polypoidal lesions
      that were confirmed by indocyanine green angiography. RESULTS: OCT showed double
      reflective layers that consisted of retinal pigment epithelium (RPE) and another
      highly reflective layer beneath the RPE ("double-layer sign") in the area of the
      branching network vessels in 26 (59%) of 44 eyes. The remaining 18 eyes had no
      double-layer sign, but 17 (94%) of 18 eyes had a slightly elevated RPE. A serous
      retinal detachment was present in 23 (88%) of 26 eyes with a double-layer sign,
      while only 1 (6%) of 18 eyes without the sign had a serous retinal detachment.
      CONCLUSIONS: In PCV, the double-layer sign is seen frequently in the area of the
      network vessels, particularly in eyes with a serous retinal detachment. The sign
      may reflect fluid accumulation between RPE and Bruch membrane resulting from
      leakage from the network of abnormal vessels.

PMID- 17558322
TI  - Macular microholes.
AB  - PURPOSE: To describe the clinical features and natural course of microholes of
      the macula. METHODS: We reviewed the charts of 31 patients (35 eyes) with
      punctate foveal defects, or "microholes," of the macula. Patients were seen
      between 1980 and 2005 at a tertiary referral center. Clinical, photographic, and
      optical coherence tomography findings were reviewed. RESULTS: All eyes had one or
      more well defined, punctate foveal lesions 35 microm to 150 microm in size. There
      was no gender predilection, and patient ages ranged from 6 years to 69 years.
      Visual acuity was > or =20/40 in 29 of 35 eyes. None of the eyes had foveal
      transmission defects shown by fluorescein angiography. A defect in the outer
      retina was demonstrated in five of seven patients who underwent optical coherence
      tomography. The lesions were nonprogressive, with no patients developing stage 3
      or 4 macular holes. CONCLUSION: Macular microholes are small lamellar defects in
      the outer retina or retinal pigment epithelium that occur through a variety of
      mechanisms, including spontaneous vitreoretinal interface changes, trauma,
      phototoxicity, and other unrecognized causes. The condition is nonprogressive,
      occurs in patients of all ages, and is compatible with good visual acuity.

PMID- 17558323
TI  - Natural course of visual field loss in patients with Type 2 Usher syndrome.
AB  - PURPOSE: To evaluate the natural course of visual field loss in patients with
      Type 2 Usher syndrome and different patterns of visual field loss. METHODS: Fifty
      eight patients with Type 2 Usher syndrome who had at least three visual field
      measurements during a period of at least 3 years were studied. Kinetic visual
      fields measured on a standard calibrated Goldmann perimeter with II4e and V4e
      targets were analyzed. The visual field areas in both eyes were determined by
      planimetry with the use of a digitalizing tablet and computer software and
      expressed in square inches. The data for each visual field area measurement were
      transformed to a natural log unit. Using a mixed model regression analysis,
      values for the half-life of field loss (time during which half of the remaining
      field area is lost) were estimated. Three different patterns of visual field loss
      were identified, and the half-life time for each pattern of loss was calculated.
      RESULTS: Of the 58 patients, 11 were classified as having pattern type I, 12 with
      pattern type II, and 14 with pattern type III. Of 21 patients whose visual field
      loss was so advanced that they could not be classified, 15 showed only a small
      residual central field (Group A) and 6 showed a residual central field with a
      peripheral island (Group B). The average half-life times varied between 3.85 and
      7.37 for the II4e test target and 4.59 to 6.42 for the V4e target. There was no
      statistically significant difference in the half-life times between the various
      patterns of field loss or for the test targets. CONCLUSION: The average half-life
      times for visual field loss in patients with Usher syndrome Type 2 were
      statistically similar among those patients with different patterns of visual
      field loss. These findings will be useful for counseling patients with Type 2
      Usher syndrome as to their prognosis for anticipated visual field loss.

PMID- 17558324
TI  - Risk for eye splash injury during administration of intraocular injections: a
      study of retina specialists and fellows.
AB  - OBJECTIVE: To evaluate the use of eye protection and frequency of eye splash
      events during intraocular injections as well as infection risk awareness among
      retina specialists and fellows in training. METHODS: In a prospective survey of
      practicing retina specialists and retina fellows, frequency of use and type of
      eye protection employed during intraocular injections, frequency of eye splash
      occurrences, description of the eye splash event, number of procedures performed,
      and awareness of transconjunctival infection risk were investigated. RESULTS:
      Sixty-four ophthalmologists responded to the questionnaire: 40 retina fellows and
      24 retina specialists. The response rate was 100%. Twenty-five percent of the
      fellows and 33.3% of the specialists reported using eye protection, including
      corrective glasses, during all intraocular injections. Two of the retina fellows
      and none of the specialists used special forms of eye protection. Retina fellows
      had a mean +/- SD of 2.1 +/- 1.3 years experience and the specialists had a mean
      +/- SD of 10.4 +/- 6.7 years experience in performing intraocular injections. The
      mean number of injections +/- SD performed by the fellows and specialists was 23
      +/- 14.6 and 35 +/- 11.9 per month, respectively. Twelve conjunctival or corneal
      splash occurrences were reported by six fellows and two retina specialists.
      Eleven splash events occurred due to reflux of fluid during administration of
      subconjunctival anesthetic injection, and one event occurred during an anterior
      chamber tap. Splash events were significantly more likely to occur during
      procedures performed by fellows, with a relative risk of 8.4 for unprotected
      procedures (P< 0.001, Fisher exact test). Most (87.5%) of the participants were
      aware of the risk for transconjunctival viral infection. CONCLUSION: Special eye
      protection is seldom used during administration of intraocular injections.
      Although the risk for eye splash during administration of subconjunctival
      anesthetic before intraocular injections is relatively small, protective measures
      may be considered when treating high-risk patients.

PMID- 17558325
TI  - A new heavy silicone oil (HWS 46-3000) used as a prolonged internal tamponade
      agent in complicated vitreoretinal surgery: a pilot study.
AB  - PURPOSE: To report the results of a prospective pilot study using a new heavy
      agent, HWS 46-3000, as long-term endotamponade in complicated retinal detachment.
      METHODS: Thirty-two consecutive patients were enrolled in the study. Indications
      for enrollment included retinal detachment with proliferative vitreoretinopathy
      arising from inferior or posterior tears. The patients underwent pars plana
      vitrectomy, membrane peeling, and HWS 46-3000 filling. Follow-up examinations
      were scheduled at 1 day to 7 days and 1 month to 3 months after initial surgery
      and 7 days and 1 month to 6 months after endotamponade removal. RESULTS: At
      baseline examination, mean best-corrected Snellen visual acuity was 2.44
      logarithm of the minimal angle of resolution (logMAR). HWS 46-3000 was removed
      after 45 days to 96 days. Initial retinal reattachment was achieved in all eyes.
      HWS 46-3000 endotamponade was associated with a success rate of 84.6% with a
      single surgery and an overall success rate of 100% at 6 months with the second
      operation and conventional silicone oil endotamponade. At 6 months, mean best
      corrected visual acuity was +1.09 logMAR (P < 0.0001). Complications were
      posterior subcapsular cataract formation (100%), membrane formation (3 eyes, 9%),
      and increased intraocular pressure (1 eye). Emulsification and intraocular
      inflammation were not observed. CONCLUSION: HWS 46-3000 was well tolerated,
      effective in the inferior quadrants with a low incidence of membrane development.
      The main complication was the high rate of tamponade-related cataract formation.

PMID- 17558326
TI  - Evaluation of costs for cystoid macular edema among patients after cataract
      surgery.
AB  - PURPOSE: Little is known about the costs of cystoid macular edema (CME), an
      important complication associated with cataract surgery. The purpose of this
      analysis was to estimate the cost of treatment for CME in the United States.
      METHODS: Data were analyzed from the 1997 through 2001 Medicare 5% Beneficiary
      Encrypted Files. Beneficiaries who underwent cataract surgery were identified and
      stratified by diagnosis of CME (cases) or no diagnosis of CME (controls) within 1
      year after surgery. Claims and reimbursements for ophthalmic care were
      identified. Subgroup analyses explored CME costs among beneficiaries with
      diabetes versus those without diabetes. RESULTS: Of 139,759 beneficiaries with
      cataract surgery, 1.95% (2,720) were diagnosed with CME. Annual total ophthalmic
      claims were 41% ($3,298) higher for cases than for controls; payments were 47%
      ($1,092) higher (both P < 0.0001). Approximately 16% (23,122) of cataract
      patients had diabetes. The rate of CME diagnosis was significantly higher for
      diabetics than for nondiabetics (3.05% vs. 1.73%, respectively). Differences in
      claims and payments between cases and controls were similar for diabetic and
      nondiabetic subgroups. CONCLUSION: CME is associated with substantial costs.
      Therapies that prevent or decrease CME severity are likely to result in cost
      savings, particularly among diabetic beneficiaries. Further analyses should
      explore the relationship of comorbidities to costs among CME patients.

PMID- 17558327
TI  - Retinal pigment epithelium produces matrix metalloproteinases after laser
      treatment.
AB  - PURPOSE: To evaluate production of matrix metalloproteinases (MMPs) and tissue
      inhibitors of metalloproteinases (TIMPs) after panretinal photocoagulation (PRP)
      of human retinal pigment epithelium (RPE) explants. METHODS: Treated explants
      were subjected to substrate zymography to differentiate MMP-2 from MMP-9 and dot
      immunoblot analysis to quantify MMP-3 and TIMP activity. Tritiated thymidine
      uptake by RPE cells was measured to document evidence of cellular division in the
      laser-treated versus control explants. RESULTS: We detected MMP-2, MMP-3, and
      TIMP-1. MMP-2 and MMP-3 secretion increased to twice the control values. TIMP
      decreased until day 4 and then increased by day 6. Tritiated thymidine uptake
      increased 2.5-fold until day 6, returning to baseline by day 8. CONCLUSION: PRP
      disturbs MMP/TIMP balance, inhibiting the initiation and maintenance required for
      active neovascularization. The efficacy of PRP may be due to changes in the
      expression pattern of metalloproteinases and inhibitors. This model elucidates
      the possible contribution of PRP to neovascularization regression by
      demonstrating the effect of laser on TIMP/MMP balance. The effects of PRP may be
      much more complex than currently understood and most likely involve more than
      vascular endothelial growth factor and other ischemia-related factors.

PMID- 17558328
TI  - Blindness and low vision in a tertiary ophthalmologic center in Thailand: the
      importance of cytomegalovirus retinitis.
AB  - PURPOSE: To determine the causes of blindness and low vision in patients
      consulting a tertiary ophthalmologic center in northern Thailand. METHODS: The
      study population included 2,951 new consecutive patients from the Department of
      Ophthalmology at University Hospital in Chiang-Mai, Thailand. Main outcome
      measures were blindness and low vision, which were defined according to World
      Health Organization criteria. RESULTS: Of 2,951 patients, 369 (12.5%) had
      blindness and/or low vision (bilateral blindness in 73, unilateral blindness in
      129, bilateral low vision in 77, and unilateral low vision in 90). Of the
      etiological causes of visual loss, age-related ocular disease was the most
      frequent (128 patients [35%]) followed by infections (66 patients [18%]) and
      trauma (43 patients [12%]). Although infections and trauma were the predominant
      causes of blindness, age-related disorders were frequently found in patients with
      low vision. Of anatomical sites, the lens (134 patients [36%]) was the main
      location of visual loss, closely followed by disorders of the retina and/or uvea
      (126 patients [34%]). Blindness and low vision were considered avoidable in 70%
      of cases. Of 73 patients with bilateral blindness, 14 had active cytomegalovirus
      retinitis, accounting for 19% of all patients with bilateral blindness.
      CONCLUSION: The most common causes of blindness and low vision in a tertiary
      center in northern Thailand were age-related ocular disorders and infections,
      which were predominantly cases of cytomegalovirus retinitis in human
      immunodeficiency virus-infected patients.

PMID- 17558329
TI  - Diagnostic and therapeutic challenges.

PMID- 17558330
TI  - Double macular hole in vitreomacular traction syndrome.

PMID- 17558331
TI  - Genotyping of Pneumocystis jiroveci pneumonia in Italian AIDS patients. Clinical
      outcome is influenced by dihydropteroate synthase and not by internal transcribed
      spacer genotype.
AB  - BACKGROUND: Two Pneumocystis jiroveci independent genomic regions, internal
      transcribed spacer (ITS) 1 and ITS2, and dihydropteroate synthase (DHPS) gene
      have been used for typing a cohort of HIV-infected Italian patients with P
      jiroveci pneumonia (PcP). METHODS: Bronchoalveolar lavage samples isolated from
      207 HIV-infected adults were ITS and DHPS genotyped by DNA sequencing and by
      restriction fragment length polymorphism analysis, respectively. Mutant DHPS
      samples were cloned and ITS typed. Data on severity, treatment, and outcome of
      PcP were obtained by chart review. RESULTS: High diversity with 46 different ITS
      genotypes was observed. At the DHPS locus, 9.1% of samples analyzed were found to
      be mutated. A correlation was observed between DHPS mutants and greater severity
      of PcP, as defined by higher lactate dehydrogenase (P = 0.015) and need for
      intubation (P = 0.002), and worse outcomes, as defined by failure of sulfa
      treatment (P = 0.04), death, and/or relapse of PcP (P = 0.008). There was a
      significant difference in ITS genotype patterns between DHPS wild-type and
      mutants (P = 0.028). CONCLUSIONS: The present data suggest the absence of a
      correlation between P jiroveci ITS types and specific clinical characteristics.
      DHPS mutations correlate with possible failure of anti-P jiroveci sulfa therapy,
      and a trend of association is shown between DHPS mutations and some clinical PcP
      features.

PMID- 17558332
TI  - Comparison of clinical response to initial highly active antiretroviral therapy
      in the patients in clinical care in the United States and Brazil.
AB  - BACKGROUND: US and Brazilian studies indicate that highly active antiretroviral
      therapy (HAART) has been effective in reducing morbidity and mortality from
      HIV/AIDS. Differences exist in the adoption and patterns of antiretroviral drug
      use and in the incidence of AIDS-defining illness (ADI) between the 2 countries,
      however, and there has not been a direct comparison of clinical response between
      Brazil and the United States. We sought to determine if there have been
      differences in the clinical response to HAART from HIV clinical practices in the
      United States and Brazil. METHODS: We compared 2 similarly designed clinical
      cohorts from Baltimore, Maryland and Rio de Janeiro, Brazil. Patients who started
      HAART from 1997 to 2004 were compared for HIV-1 RNA suppression and CD4+ T
      lymphocyte count change by 1 year of therapy and for development of an ADI up to
      6 years of follow-up. A total of 1368 patients from Baltimore and 1045 patients
      from Rio de Janeiro were studied. RESULTS: There was no difference by location in
      achieving an HIV-1 RNA level <400 copies/mL (46.9% in Rio de Janeiro, 50.8% in
      Baltimore), in the log change in HIV-1 RNA level (-1.65 log in Rio de Janeiro, -
      1.63 log in Baltimore), or in the change in CD4 count (116 cells/mm3 in Rio de
      Janeiro, 122 cells/mm3 in Baltimore) by 12 months after starting HAART. By Kaplan
      Meier analysis and Cox regression adjusted for demographic and clinical
      prognostic factors, there was no difference by location in development of the
      first ADI after starting HAART (relative hazard = 1.02; 95% confidence interval:
      0.82 to 1.25 for Rio de Janeiro vs. Baltimore). The most commonly occurring ADI
      in Rio de Janeiro was tuberculosis (27.7% of patients), and the most commonly
      occurring ADI in Baltimore was esophageal candidiasis (36.8% of patients).
      CONCLUSIONS: There were only minor differences in clinical response to the use of
      HAART comparing Rio de Janeiro with Baltimore, despite differences in patterns of
      antiretroviral drug use and ADI incidence. This analysis indicates that HAART can
      be similarly effective in treating HIV/AIDS in countries with different
      economies.

PMID- 17558333
TI  - Adherence to antiretroviral therapy in patients receiving free treatment from a
      government hospital in Blantyre, Malawi.
AB  - OBJECTIVES: To compare 3 measures of adherence to antiretroviral therapy (ART) in
      HIV-positive adults receiving free treatment from a public hospital in Malawi.
      METHODS: Adherence was measured over 1 month by pill count (PC), self-report, and
      a medication event monitoring system RESULTS: Data from 80 patients were
      available for analysis. The mean patient age was 38.6 years, and 57.5% were
      female. The mean adherence using the MEMS cap (MC) was 88.1%. Forty-six (57.5%)
      patients had MC adherence > or =95%, and 13 (16.2%) had <80% adherence. There was
      no association between MC adherence and time on ART. Mean PC adherence was 98.6%,
      significantly higher than MC adherence (P < 0.001). There was no clear relation
      between PC and MC adherence: 4 patients had MC adherence <20% but PC adherence of
      100%. Self-reports of missing a tablet did not correlate with poor MC adherence.
      CONCLUSIONS: The study shows the complexities of measuring adherence and probable
      overestimation of adherence by PC and self-report. Because these are the main
      methods used in developing countries, this raises concerns about the development
      of drug resistance. Improved methods are needed to detect nonadherence in
      developing countries, and validation of MC data with drug levels and virologic
      outcome in this setting is important.

PMID- 17558334
TI  - Innate immunity in HIV infection: enhanced susceptibility to CD95-mediated
      natural killer cell death and turnover induced by HIV viremia.
AB  - In the present study, we performed DNA microarray analyses and phenotypic and
      functional analyses in an effort to elucidate the mechanisms by which ongoing HIV
      replication affects the physiologic function of natural killer (NK) cells.
      Functional assays confirmed an increased propensity of NK cells from HIV-infected
      viremic individuals to undergo Fas-mediated apoptosis but not CD16- or NKG2D
      mediated apoptosis. Serum levels of sFasL and expression of Ki67 on NK cells were
      markedly elevated in HIV-infected viremic individuals when compared with those of
      HIV-infected aviremic and HIV-seronegative individuals. Our data demonstrate that
      ongoing HIV replication results in profound NK-cell abnormalities that are likely
      to be attributable to the effects of virus-induced immune activation. Of note is
      an increased susceptibility to cell death mediated by CD95-sFasL interactions. In
      addition, these NK cells, particularly the CD56(dim) CD16(bright) subset, undergo
      enhanced cell turnover in vivo, as demonstrated by intracellular Ki67 expression.

PMID- 17558335
TI  - Declining HIV incidence among patients attending sexually transmitted infection
      clinics in Pune, India.
AB  - OBJECTIVE: A recent report suggesting declining HIV transmission rates in
      southern India has been based on HIV seroprevalence data to estimate HIV
      incidence. We analyzed HIV incidence rates among 3 cohorts (male, female non-sex
      worker, female sex worker [FSW]) presenting to sexually transmitted infection
      (STI) clinics in Pune, India over 10 years. METHODS: Between 1993 and 2002,
      consenting HIV-uninfected individuals were enrolled in a prospective study of the
      risks for HIV seroconversion. Standardized HIV incidence estimates were
      calculated separately for the 3 cohorts. RESULTS: HIV acquisition risk declined
      by more than 70% for FSWs (P = 0.02) and men (P < 0.001) attending the STI
      clinics. There was no significant reduction in HIV incidence among women
      attending STI clinics (P = 0.74). The decline in HIVacquisition risk among male
      patients with STIs was associated with an increase in reported condom use with
      recent FSW contact and a decrease in genital ulcer disease. CONCLUSIONS: We
      report the first direct evidence for a decline in HIV incidence rates in FSWs and
      male patients with STIs over time. The lack of change in HIV infection risk among
      non-sex worker women highlights the need for additional targeted HIV prevention
      interventions.

PMID- 17558336
TI  - The protective effect of circumcision on HIV incidence in rural low-risk men
      circumcised predominantly by traditional circumcisers in Kenya: two-year follow
      up of the Kericho HIV Cohort Study.
AB  - BACKGROUND: Three randomized controlled trials (RCTs) have demonstrated that male
      circumcision prevents female-to-male HIV transmission in sub-Saharan Africa. Data
      from prospective cohort studies are helpful in considering generalizability of
      RCT results to populations with unique epidemiologic/cultural characteristics.
      METHODS: Prospective observational cohort sub-analysis. A total of 1378 men were
      evaluated after 2 years of follow-up. Baseline sociodemographic and
      behavioral/HIV risk characteristics were compared between 270 uncircumcised and
      1108 circumcised men. HIV incidence rates (per 100 person-years) were calculated,
      and Cox proportional hazards regression analyses estimated hazard rate ratios
      (HRs). RESULTS: Of the men included in this study, 80.4% were circumcised; 73.9%
      were circumcised by traditional circumcisers. Circumcision was associated with
      tribal affiliation, high school education, fewer marriages, and smaller age
      difference between spouses (P < 0.05). After 2 years of follow-up, there were 30
      HIV incident cases (17 in circumcised and 13 in uncircumcised men). Two-year HIV
      incidence rates were 0.79 (95% confidence interval [CI]: 0.46 to 1.25) for
      circumcised men and 2.48 (95% CI: 1.33 to 4.21) for uncircumcised men
      corresponding to a HR = 0.31 (95% CI: 0.15 to 0.64). In one model controlling for
      sociodemographic factors, the HR increased and became non-significant (HR = 0.55;
      95% CI: 0.20 to 1.49). CONCLUSIONS: Circumcision by traditional circumcisers
      offers protection from HIV infection in adult men in rural Kenya. Data from well
      designed prospective cohort studies in populations with unique cultural
      characteristics can supplement RCT data in recommending public health policy.

PMID- 17558337
TI  - HIV-positive patients with nonalcoholic fatty liver disease have a lower body
      mass index and are more physically active than HIV-negative patients.
AB  - OBJECTIVE: To determine whether the clinical and metabolic features associated
      with nonalcoholic fatty liver disease (NAFLD) are similar between HIV-positive
      and HIV-negative male subjects. METHODS: Twenty-six HIV-positive and 25 HIV
      negative subjects with liver biopsy-proven NAFLD were compared for liver
      histology (extent of steatosis, steatosis grading, and fibrosis staging), blood
      biochemistry (glucose, insulin, C-peptide, hemoglobin A1c, and lipid profile),
      insulin resistance (IR) using a homeostasis model assessment, anthropometry (body
      mass index [BMI], waist circumference, and arm muscle area), dietary intake, and
      physical activity. RESULTS: The 2 groups were similar for age, liver histology,
      and IR. HIV-positive patients had a lower BMI (26.3 +/- 0.5 vs. 30.2 +/- 1.0
      kg/m; P = 0.001) and lower percentage of fat mass (19.4 +/- 0.9 vs. 22.7 +/- 1.2;
      P = 0.026) when compared with HIV-negative patients. Although caloric intake was
      similar between groups, HIV-positive patients had a higher physical activity
      level (8.3 +/- 1.6 vs. 4.1 +/- 0.8 units of exercise per day; P = 0.029). Blood
      triglycerides were significantly higher (3.14 +/- 0.39 vs. 1.86 +/- 0.20 mmol/L;
      P = 0.006) in HIV-positive patients. CONCLUSION: Although NAFLD was similar
      between the 2 groups, HIV-positive patients had a lower BMI and were more
      physically active compared with HIV-negative patients. This may suggest that in
      HIV, NAFLD is associated with factors other than those related to body fatness,
      such as HIV infection and treatment.

PMID- 17558338
TI  - Histologic changes in the breast with menopausal hormone therapy use: correlation
      with breast density, estrogen receptor, progesterone receptor, and proliferation
      indices.
AB  - OBJECTIVE: This retrospective study systematically compared mammographic density
      with histology in women receiving or not receiving menopausal hormone therapy
      (HT). DESIGN: This study was approved by the institutional review board. Twenty
      eight postmenopausal women using HT were matched with 28 postmenopausal women not
      using HT at the time of breast cancer diagnosis. Noncancerous tissue from
      mastectomy specimens was examined histologically to quantitate the content of
      fibrous stroma, ducts, and lobule types 1, 2, and 3. Tissue samples were also
      evaluated for estrogen receptor, progesterone receptor, and Ki67 activity in the
      ducts and lobules. Breast density was quantified by digitizing the contralateral
      mammogram and computer-assisted interactive thresholding. RESULTS: High breast
      density in women using HT was correlated with greater fibrous stroma (P = 0.020)
      and lobule type 1 (P = 0.016). Breast density also correlated with Ki67 activity
      in the ducts (P = 0.031) and lobules (P= 0.023) for both groups combined.
      Estrogen and progesterone receptors did not correlate with either breast density
      or HT use. CONCLUSIONS: Increased fibrous stroma and lobule type 1 are associated
      with increasing mammographic density in women using HT, independent of estrogen
      and progesterone receptor up-regulation. These findings suggest that increased
      breast density may be mediated through a paracrine effect. The increase in breast
      cancer risk with HT use may be due to an increase in target lobule type 1 cells.

PMID- 17558339
TI  - Lateral semicircular canal dehiscence.

PMID- 17558340
TI  - Coenzyme Q 10 and cardiovascular risk factors in idiopathic sudden sensorineural
      hearing loss patients.
AB  - OBJECTIVES: We investigated the association of idiopathic sudden sensorineural
      hearing loss (ISSNHL) with coenzyme Q (CoQ) and cardiovascular risk factors.
      STUDY DESIGN: A prospective study. SETTING: Hospital center. PATIENTS: Thirty
      Italian patients with ISSNHL and 60 healthy Italian subjects. INTERVENTION:
      Diagnostic. MAIN OUTCOME MEASURES: Evaluation of serum CoQ levels and
      cardiovascular risk factors (total cholesterol, low-density lipoprotein [LDL],
      homocysteine [HCY]). The results were compared with variance analysis and
      Student's t test. Univariate and multivariate analysis were used to evaluate the
      association between ISSNHL and CoQ, total cholesterol, LDL, and HCY levels.
      RESULTS: In our series, we found a significant association between ISSNHL and
      high total cholesterol (p < 0.05), high LDL (p = 0.021), and low CoQ (p < 0.05)
      levels. We did not find a significant association between ISSNHL and HCY levels.
      In the univariate analysis, low levels of CoQ, high levels of total cholesterol,
      and LDL were found to be significantly associated with ISSNHL. In the
      multivariate analysis, only high levels of total cholesterol and low levels of
      CoQ remained significantly associated with a high risk of sudden sensorineural
      hearing loss. CONCLUSION: The studies regarding the role of cardiovascular risk
      factors in ISSNHL are not conclusive. This is the first report regarding the
      association of ISSNHL and low serum levels of the antioxidant CoQ. Further
      studies are needed to investigate the role of antioxidants, including CoQ, in
      ISSNHL.

PMID- 17558341
TI  - Scalar localization of the electrode array after cochlear implantation: clinical
      experience using 64-slice multidetector computed tomography.
AB  - OBJECTIVE: To use the improved resolution available with 64-slice multidetector
      computed tomography (MDCT) in vivo to localize the cochlear implant electrode
      array within the basal turn. STUDY DESIGN: Sixty-four-slice MDCT examinations of
      the temporal bones were retrospectively reviewed in 17 patients. Twenty-three
      implants were evaluated. SETTING: Tertiary referral facility. PATIENTS: All
      patients with previous cochlear implantation evaluated at our center between
      January 2004 and March 2006 were offered a computed tomographic examination as
      part of the study. In addition, preoperative computed tomographic examinations in
      patients being evaluated for a second bilateral device were included.
      INTERVENTION: Sixty-four-slice MDCT examination of the temporal bones. MAIN
      OUTCOME MEASURE: Localization of the electrode array within the basal turn from
      multiplanar reconstructions of the cochlea. RESULTS: Twenty-three implants were
      imaged in 17 patients. We were able to localize the electrode array within the
      scala tympani within the basal turn in 10 implants. In 3 implants, the electrode
      array was localized to the scala vestibuli. Migration of the electrode array from
      scala tympani to scala vestibuli was observed in three implants. Of the 7
      implants in which localization of the electrode array was indeterminate, all had
      disease entities that obscured the definition of the normal cochlear anatomy.
      CONCLUSIONS: Sixty-four-slice MDCT with multiplanar reconstructions of the
      postoperative cochlea after cochlear implantation allows for accurate
      localization of the electrode array within the basal turn where normal cochlear
      anatomy is not obscured by the underlying disease process. Correlating the
      position of the electrode in the basal turn with surgical technique and implant
      design could be helpful in improving outcomes.

PMID- 17558342
TI  - The role of CMV inflammatory genes in hearing loss.
AB  - HYPOTHESIS: The purpose of this study is to test the hypothesis that virally
      encoded immunomodulatory genes play a role in cytomegalovirus (CMV)-related
      hearing loss. OBJECTIVE: Cytomegalovirus is the leading cause of infectious
      related congenital sensorineural hearing loss worldwide. Unfortunately, little is
      known about the pathophysiology of CMV-related injury to the developing ear.
      METHODS: Viral mutagenesis techniques were developed that allow the deletion of a
      specific viral immunomodulatory gene, macrophage inflammatory protein (MIP)
      1alpha homolog. We assessed the extent to which this gene product contributed to
      auditory pathologic findings in the guinea pig (GP) model. Eighteen weanling GPs
      (250-350 g) were used under an Institutional Animal Control and Use Committee
      approved protocol. We analyzed preinoculation hearing using auditory brainstem
      response recordings. Intracochlear inoculations were performed on one group of
      six GPs with sterile viral media, 6 GPs with wild-type (WT) CMV virus, and 6 GPs
      with mutant "knockout" (KO) virus (with deleted MIP-1alpha homolog). Auditory
      brainstem responses were then obtained on postinoculation Days 7, 14, 21, and 28.
      RESULTS: There was a significant difference in hearing between the KO group and
      the WT group, with significantly better hearing in the KO group. A comparison of
      the KO group to the sham group revealed no significant hearing differences
      between the groups. The WT group had significant threshold shifts by dose at all
      frequencies meeting our criteria of hearing loss (>30 dB). There were no
      statistical differences in the sham or KO group. CONCLUSION: Virally encoded
      immunomodulatory genes such as MIP-1alpha seem to play a significant role in CMV
      related hearing loss. This study is the first demonstration of the role of
      specific viral immune modulation genes in the in vivo pathogenesis of CMV-induced
      hearing loss in a relevant animal model.

PMID- 17558343
TI  - Paraneoplastic effects on neurophthalmologic function.
AB  - OBJECTIVE: Paraneoplastic neurologic syndrome with otoneurophthalmologic
      manifestations is much less common than direct, metastatic, and treatment-related
      complications of cancer. Few studies have focused on patients presenting with
      paraneoplastic syndrome before a cancer is identified. PATIENT: We describe a
      case of combined paraneoplastic brainstem/limbic encephalitis and Lambert-Eaton
      myasthenic syndrome in a patient with small cell lung cancer and positive
      antiamphiphysin antibodies who initially presented with otoneurophthalmologic
      signs and symptoms to the ears, nose, and throat clinic. To the best of the
      authors' knowledge, this combined form of disease, confirmed by both clinical and
      laboratory tests, is one of the rarest cases ever to be reported. Immunoglobulin
      G polyclonal antibodies directed against amphiphysin have been detected in a few
      stiff-person syndrome patients, especially those with breast cancer. This case is
      again unusual in the sense that the patient was positive for antiamphiphysin
      antibodies, but negative for anti-Hu antibodies. CONCLUSION: Patients initially
      presenting with otoneurophthalmologic signs and symptoms with no detectable
      lesions in the central nervous system should be promptly and thoroughly
      investigated and monitored carefully for a possible malignancy elsewhere in their
      bodies without waiting for the actual malignancy to manifest itself at a later
      stage, thus increasing the prospect of detecting the malignancy and optimizing
      the treatment modalities at an earlier stage.

PMID- 17558345
TI  - A novel selective extracorporeal intervention in sepsis: immunoadsorption of
      endotoxin, interleukin 6, and complement-activating product 5a.
AB  - In sepsis, endotoxin, interleukin 6 (IL-6), and complement-activation product 5a
      (C5a) trigger inflammatory cascades resulting in monocytic deactivation. When
      this occurs, the outcome is often uncontrolled infection, multiple organ
      dysfunction, and death. We tested here whether simultaneous reduction of systemic
      endotoxin, IL-6, and C5a levels could be achieved via selective extracorporeal
      immunoadsorption (IA) and whether this would restore monocytic responsiveness and
      improve organ function. Therefore, 33 patients with severe sepsis or septic shock
      were enrolled in a prospective, 1:2 case-control matched, blinded endpoint
      evaluation trial. In addition to best supportive care, 11 of these patients (mean
      age, 57.8 +/- 2.2 years; Acute Physiology and Chronic Health Evaluation II score,
      23.7 +/- 1.6) received simultaneous endotoxin IA, IL-6 IA, and C5a IA on 5
      consecutive days for 7.5 h each. Our observational end points were the course of
      monocytic immunity (monocytic HLA-DR expression) and other indices of
      inflammation and disease severity. In patients receiving IA, the mean circulating
      level of IL-6 was reduced from 361.7 +/- 116.0 to 38.2 +/- 15.2 pg/mL (P = 0.02),
      and of C5a from 297.6 +/- 43.1 to 79.2 +/- 14.5 ng/mL (P < 0.001). Two indices of
      endotoxemia were reduced also. Treated patients had lower C-reactive protein and
      Acute Physiology and Chronic Health Evaluation II scores at day 7 (P = 0.004 and
      P = 0.0001, respectively). Monocytic HLA-DR improved in the treated patients but
      not in controls (P < 0.0001). Under treatment, HLA-DR was found to recover in all
      patients with immunoparalysis (4,993.6 +/- 1,162 to 15,295.3 +/- 2,197 molecules
      per cell; P = 0.002). Here, we demonstrate that simultaneously reducing
      circulating endotoxin, IL-6, and C5a levels by selective IA reverses monocytic
      deactivation and improves organ system functions. This novel strategy might open
      a new therapeutic avenue for an interventional extracorporeal treatment of
      patients with sepsis.

PMID- 17558346
TI  - L-arginine attenuates acute lung injury after smoke inhalation and burn injury in
      sheep.
AB  - Thermal injury results in reduced plasma levels of arginine (Arg). With reduced
      Arg availability, NOS produces superoxide instead of NO. We hypothesized that Arg
      supplementation after burn and smoke inhalation (B + S) injury would attenuate
      the acute insult to the lungs and, thus, protect pulmonary function. Seventeen
      Suffolk ewes (n = 17) were randomly divided into three groups: (1) sham injury
      group (n = 6), (2) B + S injury plus saline treatment (n = 6), and (3) B + S
      injury plus L-ARG infusion at 57 mg.kg(-1).h(-1) (n = 5). Burn and smoke
      inhalation injury was induced by standardized procedures, including a 40% area
      full thickness flame burn combined with 48 breaths of smoke from burning cottons.
      All animals were immediately resuscitated by Ringer solution and supported by
      mechanical ventilation for 48 h, during which various variables of pulmonary
      function were monitored. The results demonstrated that Arg treatment attenuated
      the decline of plasma Arg concentration after B + S injury. A higher plasma Arg
      concentration was associated with a less decline in Pao2/Fio2 ratio and a reduced
      extent of airway obstruction after B + S injury. Histopathological examinations
      also indicated a remarkably reduced histopathological scores associated with B +
      S injury. Nitrotyrosine stain in lung tissue was positive after B + S injury, but
      was significantly reduced in the group with Arg. Therefore, L-Arg supplementation
      improved gas exchange and pulmonary function in ovine after B + S injury via its,
      at least in part, effect on reduction of oxidative stress through the
      peroxynitrite pathway.

PMID- 17558347
TI  - Uncontrolled hemorrhage differs from volume- or pressure-matched controlled
      hemorrhage in swine.
AB  - Controversy continues as to whether uncontrolled or controlled hemorrhage is the
      most appropriate for the study of hemorrhagic shock and resuscitation. To
      appraise differences between these models, we evaluated the relationship between
      blood volume loss and blood pressure in controlled versus uncontrolled
      hemorrhage. Anesthetized, instrumented, immature female pigs (40 kg) were
      assigned to one of three groups: (1) group U, uncontrolled aortotomy hemorrhage
      from a 2-mm aortotomy; (2) group P, controlled hemorrhage matched to the blood
      pressure profile of group U; or (3) group V, controlled hemorrhage matched to the
      blood volume loss profile of group U. A computer-driven feedback control system
      duplicated the group U profiles. Pigs were monitored for 3 h after hemorrhage and
      received no fluid resuscitation. Group U resulted in a blood loss of 17.6 +/- 0.7
      mL kg(-1) and a reduction in blood pressure to 28 +/- 3 mmHg at the end of active
      bleeding. Group P pigs required more blood loss (21.5 +/- 1.2 mL kg(-1)) to match
      profiles of group U blood pressure, whereas group V pigs resulted in a higher
      mean arterial pressure (42 +/- 5 mmHg) to match group U blood volume loss
      profiles. Neither heart rate nor total peripheral resistance differed
      significantly among the three groups. At the level of blood loss observed in this
      study, fundamental physiological differences existed between uncontrolled
      hemorrhage and controlled hemorrhage when matched for pressure or volume. We
      suggest that the relationship of blood pressure to blood volume loss is modified
      in the presence of uncontrolled hemorrhage.

PMID- 17558348
TI  - Identification and characterization of a dysfunctional cardiac myocyte phenotype:
      role of bacteria, Toll-like receptors, and endothelin.
AB  - Cardiac myocyte dysfunction is clearly identified as underlying the acute heart
      failure associated with bacterial infection, as well as the chronic syndrome
      following cardiac damage, but the mechanisms leading to dysfunction in each case
      are not fully established. It is thought that local hormones such as endothelin 1
      (ET-1) can increase the risk of heart failure in acute or chronic conditions. In
      the current study, we characterize myocytes as populations and identify a novel
      phenotype of the ventricular cardiac myocyte that does not contract appropriately
      on electrical stimulation. The noncontractile cardiac myocytes were viable and
      had normal calcium transients. The proportion of noncontractile cardiac myocytes
      was increased by bacteria (gram-positive Staphylococcus aureus or gram-negative
      Escherichia coli). Using selective ligands or myocytes from genetically modified
      mice, we established that the effects of S. aureus were mediated by Toll-like
      receptor 2/6 and of E. coli by Toll-like receptor 4. The transition to the
      noncontractile phenotype was strongly inhibited by ETA antagonism but unaffected
      by inhibition of NOS, suggesting that ET-1 and not NO mediates this phenomenon.
      These results are the first to describe the characteristics of this
      noncontractile phenotype and the mechanisms of its induction by bacteria.
      Description of the myocyte population, instead of effects only on individual
      cells, will be more relevant to the prediction of the depression of cardiac
      function.

PMID- 17558349
TI  - Increased plasma levels of soluble triggering receptor expressed on myeloid cells
      1 and procalcitonin after cardiac surgery and cardiac arrest without infection.
AB  - Soluble triggering receptor expressed on myeloid cells 1 (sTREM-1) and
      procalcitonin (PCT) are often considered to be specific markers for infection. We
      evaluated plasma levels of sTREM-1 and PCT in patients with systemic inflammatory
      response syndrome but no sepsis. Noninfected patients undergoing elective heart
      surgery with cardiopulmonary bypass (n = 76) and patients admitted after out-of
      hospital cardiac arrest (n = 54) were followed up for 3 days. Patients with
      severe sepsis (n = 55) and healthy volunteers (n = 31) were included as positive
      and negative controls, respectively. Plasma levels of PCT were higher in sepsis
      patients than in patients who survived after cardiac arrest or after heart
      surgery. In contrast, peak plasma levels of sTREM-1 in heart surgery and in
      cardiac arrest patients overlapped with those measured in patients with sepsis.
      Both sTREM-1 and PCT were significantly higher in cardiac arrest patients who
      died of refractory shock than in those who died of neurological failure or
      survived without major neurological damage. In the cardiac arrest patients with
      refractory shock, sTREM-1 and PCT levels were similar to those in the patients
      with severe sepsis. In conclusion, sTREM-1 and PCT are not specific for infection
      and can increase markedly in acute inflammation without infection.

PMID- 17558350
TI  - Resuscitation from hemorrhagic shock with hydroxyethyl starch and coagulation
      changes.
AB  - Administration of fluids to maintain or restore intravascular volume is a common
      intervention after hemorrhagic shock, but there is uncertainty whether the choice
      of fluid significantly influences outcome. Systemic parameters, microvascular
      perfusion, and functional capillary density were used to characterize
      resuscitation from hemorrhagic shock with hydroxyethyl starch (HES) of different
      molecular weights. Studies were made in the hamster window chamber model to
      determine their effects on blood rheological properties, restoration of perfusion
      and coagulation changes. Moderate hemorrhagic shock was induced by controlled
      arterial bleeding of 50% of blood volume, and hypovolemia was maintained for 1 h
      before resuscitation. Twenty-five percent of blood volume was restituted, and
      recovery was followed over 60 min. Low-molecular weight (MW) HES (L-HES) 130 kd,
      degree of substitution (DS) 0.40, and high-MW HES (H-HES) 670 kd, DS 0.75, were
      used as resuscitation fluids. Microthrombi formation was induced by endothelial
      laser irradiation. H-HES improved systemic conditions, microcirculatory flow, and
      metabolic recovery after resuscitation when compared with L-HES. Mean arterial
      pressure was significantly improved after resuscitation with H-HES compared with
      L-HES, but lower than baseline and the sham group. Thrombus formation was
      impaired in both groups after resuscitation compared with sham. There was no
      difference in microthrombi formation between low- and H-HES for medium and large
      laser endothelial injuries. Our results indicate that fluid resuscitation with
      HES may increase the risk of bleeding, but not necessarily caused by the
      properties (MW and DS) of the colloid. Impairment of thrombus formation seems to
      be in part related to altered hemodynamics and transport inherent to
      hemodilution, leading to lowered platelet availability due to hemodilution and
      increased shear stress at the vessel wall when plasma viscosity is increased. The
      HES MW does not seem to be a factor in compromising platelet adherence on
      stimulated endothelium. The longer initial intravascular persistence of H-HES
      might result in longer-lasting volume effects.

PMID- 17558351
TI  - Toll-like receptor 2 participates in the response to lung injury in a murine
      model of pulmonary contusion.
AB  - Blunt chest trauma resulting in pulmonary contusion with an accompanying acute
      inflammatory response is a common but poorly understood injury. We report that
      Toll-like receptor (TLR) 2 participates in the inflammatory response to lung
      injury. To show this, we use a model of pulmonary contusion in the mouse that is
      similar to that observed clinically in humans based on histologic, morphologic,
      and biochemical criteria of acute lung injury. The inflammatory response to
      pulmonary contusion in our mouse model is characterized by pulmonary edema,
      neutrophil transepithelial migration, and increased expression of the innate
      immunity proinflammatory cytokines IL 1beta and IL 6, the adhesion intracellular
      adhesion molecule 1, and chemokine (CXC motif) ligand 1. Compared with wild-type
      animals, contused Tlr2(-/-) mice have significantly reduced pulmonary edema and
      neutrophilia. These findings are associated with decreased levels of circulating
      chemokine (CXC motif) ligand 1. In contrast, systemic IL 6 levels remain elevated
      in the TLR2-deficient phenotype. These results show that TLR2 has a primary role
      in the neutrophil response to acute lung injury. We suggest that an unidentified
      noninfectious ligand generated by pulmonary contusion acts via TLR2 to generate
      inflammatory responses.

PMID- 17558352
TI  - Ventilator-induced injury augments interleukin-1beta production and neutrophil
      sequestration in lipopolysaccharide-treated lungs.
AB  - Mechanical ventilators are commonly used to support critically ill patients;
      however, inappropriate ventilator settings might initiate or augment lung injury.
      To determine whether a large tidal volume (Vt) augments inflammatory responses
      and neutrophil sequestration in the lungs of rats receiving intratracheal
      lipopolysaccharides (LPS). Rats received intratracheal instillation of LPS (0.5
      mg/kg) followed by 4 h of mechanical ventilation (MV) at 60 strokes per min with
      a Vt of 10 mL/kg as control MV, or 30 strokes per min with a Vt of 20 mL/kg of
      body weight as high-volume MV (HMV). In addition, monoclonal antibodies against
      rat intercellular adhesion molecule 1 (ICAM-1) or immunoglobulin G (50 mg/kg)
      were administered 30 min before LPS instillation and MV. Our study demonstrates
      that HMV enhances pulmonary permeability and induces neutrophil recruitment into
      the alveolar space and pulmonary edema. Intratracheal instillation of LPS caused
      marked lung injury, neutrophil recruitment, and production of cytokines and
      chemokines. Combining LPS instillation and HMV synergistically upregulated
      interleukin 1beta (IL-1beta) production and neutrophil sequestration in lung
      tissues. The ICAM-1 expression in lung tissues was responsible for the
      synergistic effects of neutrophil sequestration. Synergistic upregulation of IL
      1beta production and neutrophil sequestration was attenuated by blocking ICAM-1
      by neutralizing antibody pretreatment. High Vt MV in LPS-injured lung causes
      synergistic production of IL-1beta and sequestration of neutrophil via ICAM-1
      dependent effects.

PMID- 17558353
TI  - Activated protein C suppresses adrenomedullin and ameliorates lipopolysaccharide
      induced hypotension.
AB  - Activated protein C (APC) is an important modulator of vascular function that has
      antithrombotic and anti-inflammatory properties. Studies in humans have shown
      modulation of endotoxin-induced hypotension by recombinant human APC, drotrecogin
      alfa (activated), however, the mechanism for this effect is unclear. We have
      found that APC suppresses the induction of the potent vasoactive peptide
      adrenomedullin (ADM) and could downregulate lipopolysaccharide (LPS)-induced ADM
      messenger RNA (mRNA) and nitrite levels in cell culture. This effect was
      dependent on signaling through protease-activated receptor 1. Addition of 1400W,
      an irreversible inducible nitric oxide synthase (iNOS) inhibitor, inhibited LPS
      induced ADM mRNA, suggesting that ADM induction is NO mediated. Furthermore, in a
      rat model of endotoxemia, APC (100 microg/kg, i.v.) prevented LPS (10 mg/kg,
      i.v.)-induced hypotension, and suppressed ADM mRNA and protein expression. APC
      also inhibited iNOS mRNA and protein levels along with reduction in NO by
      products (NOx). We also observed a significant reduction in iNOS-positive
      leukocytes adhering to vascular endothelium after APC treatment. Moreover, we
      found that APC inhibited the expression of interferon-gamma (IFN-gamma), a potent
      activator of iNOS. In a human study of LPS-induced hypotension, APC reduced the
      upregulation of plasma ADM levels, coincident with protection against the
      hypotensive response. Overall, we demonstrate that APC blocks the induction of
      ADM, likely mediated by IFN-gamma and iNOS, and suggests a mechanism that may
      account for ameliorating LPS-induced hypotension. Furthermore, our data provide a
      new understanding for the role of APC in modulating vascular response to insult.

PMID- 17558354
TI  - Pancreatic duct ligation abrogates the trauma hemorrhage-induced gut barrier
      failure and the subsequent production of biologically active intestinal lymph.
AB  - The studies of the mechanisms by which trauma-hemorrhagic shock leads to gut
      injury and dysfunction have largely ignored the nonbacterial factors contained
      within the lumen of the intestine. Yet, there is increasing evidence suggesting
      that intraluminal pancreatic proteases may be involved in this process. Thus, we
      tested the hypothesis that pancreatic proteases are necessary for the trauma
      hemorrhagic shock-induced gut injury and the production of biologically active
      mesenteric lymph by determining the extent to which pancreatic duct ligation
      (PDL) would limit gut injury and mesenteric lymph bioactivity. To assess the
      effect of PDL on gut injury and dysfunction gut morphology, the mucus layer
      structure and the gut permeability were measured in the following four groups of
      male rats subjected to laparotomy (trauma) and hemorrhagic shock (pressure, 30
      mmHg for 90 min): (1) rats subjected to trauma plus sham-shock (T/SS), (2) T/SS
      rats undergoing PDL (T/SS + PDL), (3) rats subjected to trauma and hemorrhagic
      shock (T/HS), and (4) rats subjected to T/HS + PDL. The ability of mesenteric
      lymph from these four rat groups to kill endothelial cells and activate
      neutrophils was tested in vitro. The PDL did not affect any of the parameters
      studied because there were no differences between the T/SS and the T/SS + PDL
      groups. However, PDL protected the gut from injury and dysfunction because PDL
      significantly abrogated T/HS-induced mucosal villous injury, loss of the
      intestinal mucus layer, and gut permeability. Likewise, PDL totally reversed the
      endothelial cell cytotoxic activity of T/HS lymph and reduced the ability of T/HS
      lymph to prime naive neutrophils for an augmented respiratory burst. Thus, it
      seems that intraluminal pancreatic proteases are necessary for the T/HS-induced
      gut injury and the production of bioactive mesenteric lymph.

PMID- 17558356
TI  - Locomotor training: is translating evidence into practice financially feasible?
AB  - PURPOSE: Several lines of evidence suggest that locomotor training (LT)
      modalities, such as body weight-supported treadmill training (BWSTT), improves
      gait in individuals with incomplete spinal cord injury (SCI). Yet, manual BWSTT
      has been criticized for being cost prohibitive due to the number of staff
      required to perform this treatment. This study examined the financial viability
      of a LT program using manual BWSTT. METHODS: This retrospective study analyzed
      data from individuals with motor incomplete SCI who had participated in manual
      BWSTT in a hospital-based outpatient clinic between 2003 and 2005. Individuals
      were between 18 and 68 years of age and were medically stable. Descriptive
      statistics were performed to determine the mean for each of the following: date
      of injury, age, impairment, gender, total number of visits, total procedures
      billed, charges, basic reimbursement information, and costs associated with the
      treatment. RESULTS: The majority of individuals were male, classified as ASIA C,
      and had private insurance. Physical therapy evaluation, gait training, and
      therapeutic exercise were the most commonly billed procedures for all
      individuals. It was found that this locomotor training program, using the
      delivery model of one physical therapist, two physical therapy technicians, and
      one volunteer, was profitable. CONCLUSIONS: The findings from this study suggest
      that LT using manual BWSTT in a hospital-based outpatient clinic can be
      financially feasible when provided by one trained physical therapist, two
      technicians, and one well-trained volunteer.

PMID- 17558357
TI  - Giving your outpatient rehabilitation program a lift: the financial feasibility
      of body weight supported treadmill training.

PMID- 17558358
TI  - Upper extremity use in people with hemiparesis in the first few weeks after
      stroke.
AB  - The purposes of this report were to: 1) determine the amount of upper extremity
      use in people with hemiparesis post stroke during their inpatient rehabilitation
      stay, and 2) to examine the relationships between upper extremity use and
      impairments and activity limitations at this early time point after stroke. We
      studied 34 subjects with mild-to-moderate acute hemiparesis (mean time since
      stroke = 9.3 days) and 10 healthy control subjects. Upper extremity use was
      measured over 24 hours using bilateral wrist accelerometers. Upper extremity
      impairments and activity limitations were measured using standard clinical
      techniques and tests. We found that healthy control subjects use their dominant
      and nondominant upper extremities 8-9 hours per day. Hemiparetic subjects used
      their affected and unaffected upper extremities substantially less than control
      subjects, 3.3 and 6.0 hours per day, respectively. Seven of ten impairment level
      measures and each of the activity level measures were related to affected upper
      extremity use. The impairment measures that were related to upper extremity use
      were those measures that assessed the ability to activate muscles (ie active
      range of motion and force production) and the measurement of shoulder pain. Our
      data show that affected upper extremity use is minimal during the inpatient
      rehabilitation stay, especially given that patients in this setting are required
      to have 3 hours of therapy per day. We speculate that accelerometer measurements
      of upper extremity use could be used in a variety of settings and that the
      objective information they provide would be of great value to clinicians as they
      select treatments and evaluate progress.

PMID- 17558359
TI  - Continuous scale physical functional performance test: appropriateness for middle
      aged adults with and without Parkinson's disease.
AB  - PURPOSE: Functional measures are needed that are applicable to middle-aged adults
      with neurological disorders who are on the threshold of disability. One potential
      measure is the Continuous Scale Physical Functional Performance Test (CS-PFP),
      which has been normalized and validated to older adults but performance is
      unknown for adults younger than the age of 65 years with and without neurological
      disorders. The purposes of this investigation were (1) to compare scores on the
      CS-PFP of nondisabled adults in three age groups from 35 to 64 years with two
      groups of individuals older than the age of 65; (2) to determine whether there is
      a ceiling effect for nondisabled middle-aged adults; and (3) to determine whether
      performance of individuals in early stages of Parkinson's disease (PD) age 45 to
      64 years differ significantly from performance of similarly aged nondisabled
      adults. METHODS: Data were obtained from three samples: (1) 37 adults with PD (45
      54 and 55-64 years; 57% female), (2) 70 nondisabled adults (35-44, 45-54, and 55
      64 years; 69% female); (3) 72 nondisabled older adults (65-74 and 75-85 years;
      79% female). The CS-PFP was administered in a single test session for each
      subject. Analysis of variance was performed for group differences with adjustment
      of sex as a covariate followed by a Student-Newman-Keuls post hoc analysis.
      RESULTS: For nondisabled individuals, the CS-PFP total and domain scores were
      significantly lower in the oldest group (75-85 years) compared to all other age
      groups and significantly higher in the younger two groups (35-44 and 45-54 years)
      compared to the older groups. There was no ceiling effect for any domain score or
      total score for the adults younger than 65 years. For individuals with PD, both
      age groups had significantly lower scores on the CS-PFP than did the nondisabled
      counterparts. CONCLUSIONS: Results from the nondisabled middle-aged individuals
      provide comparison data to be used clinically or in investigations of middle-aged
      adults with neurological dysfunction. Comparison of middle-aged individuals with
      PD to middle-aged nondisabled adults illustrates the true extent of functional
      difficulty experienced by individuals with PD and demonstrates the importance of
      using age appropriate comparison data. The CS-PFP is particularly applicable to
      middle-aged adults with compromised functional performance for their age but is
      too high to be effectively quantified with other assessment measures.

PMID- 17558360
TI  - An intense intervention for improving gait, balance, and mobility for individuals
      with chronic stroke: a pilot study.
AB  - PURPOSE: Stroke is the leading cause of disability in the United States. At
      present, there is a paucity of experimental evidence available to indicate what
      physical therapy techniques are effective for improving mobility in an individual
      with chronic stroke. The purpose of this study was to determine the feasibility
      and effect size of an intensive mobility training program for people with chronic
      stroke. METHOD: A convenience sample of eight individuals with chronic stroke
      received an intensive mobility intervention for 3 hours per day for 10
      consecutive weekdays. Treatment outcomes were assessed using standardized
      outcomes of gait, balance, and mobility including the GAITRite to collect spatial
      and temporal parameters of gait, the Falls Efficacy Scale, Berg Balance Scale,
      Dynamic Gait Index, and Timed Up and Go. Data were collected at four different
      time points: baseline, pre-test, post-test, and 3 months after intervention.
      RESULTS: The overall effect size of the intervention was 0.72, with changes in
      balance having much greater effects than changes in gait or mobility. The group
      demonstrated an average improvement from pre- to post-tests of 12 points on the
      Berg Balance Scale where a change of 6 is considered a minimal detectable change.
      CONCLUSIONS: This intense mobility training was a feasible intervention for this
      sample and demonstrated large effect sizes for balance outcome measures. Future
      studies incorporating more participants, a standard control, and more emphasis on
      gait would provide insight into the effectiveness and clinical relevance of this
      intervention.

PMID- 17558361
TI  - Effects of hippotherapy on postural stability, in persons with multiple
      sclerosis: a pilot study.
AB  - PURPOSE: The purpose of this pilot study was to examine the effectiveness of
      hippotherapy as an intervention for the treatment of postural instability in
      individuals with multiple sclerosis (MS). SUBJECTS: A sample of convenience of 15
      individuals with MS (24-72 years) were recruited from support groups and assessed
      for balance deficits. METHODS: This study was a nonequivalent pretest-posttest
      comparison group design. Nine individuals (4 males, 5 females) received weekly
      hippotherapy intervention for 14 weeks. The other 6 individuals (2 males, 4
      females) served as a comparison group. All participants were assessed with the
      Berg Balance Scale (BBS) and Tinetti Performance Oriented Mobility Assessment
      (POMA) at 0, 7, and 14 weeks. RESULTS: The group receiving hippotherapy showed
      statistically significant improvement from pretest (0 week) to posttest (14 week)
      on the BBS (mean increase 9.15 points (x (2) = 8.82, p = 0.012)) and POMA scores
      (mean increase 5.13 (x (2) = 10.38, p = 0.006)). The comparison group had no
      significant changes on the BBS (mean increase 0.73 (x (2) = 0.40, p = 0.819)) or
      POMA (mean decrease 0.13 (x (2) = 1.41, p = 0.494)). A statistically significant
      difference was also found between the groups' final BBS scores (treatment group
      median = 55.0, comparison group median 41.0), U = 7, r = -0.49. DISCUSSION:
      Hippotherapy shows promise for the treatment of balance disorders in persons with
      MS. Further research is needed to refine protocols and selection criteria.

PMID- 17558362
TI  - Phase manipulation and walking in stroke.
AB  - PURPOSE: The purpose of this study was to investigate the effects of in- and out
      phase arm movement on upper and lower body movement patterns during walking in
      individuals with stroke. METHODS: Eight individuals (ages 14-74 years) who had
      suffered a cerebrovascular accident and walked independently participated. There
      were three separate conditions of walking at 0.22, 0.40, and 0.63 m/s: (1) with
      no upper extremity phase manipulation, (2) instructions to move the arms in-phase
      at each velocity level, (3) instructions to move the arms out-of-phase at each
      velocity level. RESULTS: With instruction to the move the arms out-of-phase, the
      arms moved more reciprocally, back and forth, coinciding with increased arm
      swing, greater transverse trunk rotation as compared to when subjects were
      instructed to move the arms in-phase. Instructions to move the arms either in- or
      out-of-phase led to coordination between arm movement frequency and stride
      frequency (1:1 frequency coordination). DISCUSSION: Stroke is the leading cause
      of disability in the United These findings showed that altered arm swing is
      constrained by an attraction to 1:1 frequency coordination. Arm swing amplitude
      was not specified; however participants swung their arms at a frequency that
      synchronized with stride frequency (1:1 coordination). Future study is still
      needed to examine how paretic arm movement affects intersegmental coordination
      during walking. Research is needed to assess the effects of imposed upper
      extremity phasing and whether training with specific phase relations facilitates
      a relatively permanent change in the intersegmental coordination and therefore
      walking function in patients who have suffered a stroke.

PMID- 17558364
TI  - Neuroinfections in developed versus developing countries.
AB  - In recent supplement of neuroendocrinology letters, first time the authors from
      West and East, North and South of EU and the "Third World" present data on
      neuroinfections in high technology society - on nosocomial meningitis and vice
      versa in low technology and income countries of sub-Saharan Africa. 14 years
      survey of 171 cases of nosocomial paediatric meningitis is presented by Rudinsky
      et al. [1] and subpopulations of Acinetobacter baumannii and Pseudomonas
      aeruginosa [1,2] within last 20 years are briefly analyzed by Huttova et al. [2]
      and Ondrusova et al. [3]. All cases were complicating high technology procedures,
      such as neurosurgery, very low birth weight neonates after shunt implants etc.
      Current problems of management of nosocomial meningitis are reviewed by Bauer et
      al. [4] and consequence of inappropriate therapy by Huttova et al. [5]. Another
      high technology associated infection is septic embolisation followed by brain
      abscess and meningitis in patients with endocarditis after cardiac surgery (Kovac
      et al.) [6]. Experience from more than 600 cases is discussed in the article by
      Karvaj et al. [7] who outlines extremely high mortality in patients with
      endocarditis embolizing to central nervous system - up to 60%. The rest of papers
      are in contrary to problems of neuroinfections in EU and US focused on meningitis
      and cerebral malaria as commonest neuroinfections in the third world: 261 cases
      of cerebral malaria are discussed in a brief research note by Sudanese team of
      tropical programme in area of famine and civil war in southern Sudan (Bartkovjak
      and Ianetti et al.) [8]. Fungal neuroinfections complicating AIDS are of
      decreasing trend as reported by Njambi et al. from Kenya [9] and data from 497
      cases from Uganda, Ethiopia and Burundi are presented by Benca et al. [10].
      Finally an outbreak of meningococcal meningitis is reported by Benca et al. [11]
      from meningitis belt in Darfur and southern Sudan. We hope that the supplement
      may show difference in etiology, risk factors, therapy and outcome of
      neuroinfections (which is a burning public health and social problem in tropics)
      in other third world countries versus developed high-tech medical settings of US,
      EU and other high income countries, as presented by Benca et al. [12].

PMID- 17558365
TI  - Etiology, risks factors, therapy of nosocomial cerebrovascular infections.
AB  - Nosocomial cerebrovacsular infections are substantial cause of mortality and
      morbidity in patients after neurosurgery. Risk factors, etiology, treatment
      strategies and outcome of nosocomial meningitis and brain abscess are briefly
      reviewed.

PMID- 17558366
TI  - National 14 years survey of 171 cases nosocomial meningitis in children and
      comparison of two periods 1993-1998 to 1999-2006.
AB  - In 1993-1998 and in 1999-2004 we have performed two surveys of pediatric
      bacterial meningitis in all 8 neurosurgery/pediatrics and infectious diseases
      departments in Slovakia. We have detected 101 and another 54 cases with
      attributable mortality of 15% and sequellae in 18%.

PMID- 17558367
TI  - Postsurgical meningitis caused by Acinetobacter baumannii associated with high
      mortality.
AB  - Twenty five (25) cases of nosocomial postsurgical meningitis due to Acinetobacter
      baumannii meningitis were compared to other 146 cases of meningitis after surgery
      caused by other pathogens. Prior neurosurgical ventriculo-peritoneal shunt
      insertion and CNS abnormality as well as very low birth weight were significant
      risk factors for acquisition of Acinetobacter baumannii meningitis. Mortality -
      40% among children with nosocomial meningitis was unacceptably high and
      significantly higher than among meningitis caused by microorganisms other than
      Acinetobacter baumannii.

PMID- 17558368
TI  - Is combination therapy with betalactam plus aminoglycoside (AGL) improving the
      outcome of nosocomial meningitis in children?
AB  - We have been unable to document a benefit of a combination of aminoglycosides
      with betalactam or carbapenem antibiotics in nosocomial meningitis. This was
      similar to the cases of sepsis, where survival of patients did not improve with
      combination therapy. Combination therapy did not increase the chance of
      appropriateness of the therapy. 30% of those on combination therapy were
      considered as inappropriately treated in comparison to 2.8% of those on
      monotherapy (p<0.01).

PMID- 17558369
TI  - Insufficient therapy for nosocomial meningitis negatively affects survival,
      sequellae and has social consequences.

PMID- 17558370
TI  - Pseudomonas aeruginosa causing nosocomial meningitis in neonates and children:
      overview of 15 cases within 10 years.
AB  - Risk factors, therapy and outcome of 15 cases of nosocomial meningitis due to
      Pseudomonas aeruginosa is reviewed. No difference in risk factors was found,
      however mortality for Ps. aeruginosa was significantly higher (33.3 vs 15.1%
      p<0.04).

PMID- 17558371
TI  - Central nervous system complications of endocarditis.
AB  - Neurologic complications of infective endocarditis, risk factors for mortality
      and neurologic sequellae are briefly reviewed.

PMID- 17558372
TI  - Fungal neuroinfections: rare disease but unacceptably high mortality.
AB  - Within last 25 years we have observed 20 cases of fungal meningitis and/or
      cerebral abscesses. Commonest etiologic agens was Candida spp. (C. albicans 9 of
      20). Molds were responsible for 4 cases of brain abscess. Mortality was 50% what
      seems to be very high. Extremely high mortality is caused by delayed onset of
      therapy, severe underlying disease and multiresistant fungal organisms such as
      Mucorales, Fusarium solani and Aureobasidium.

PMID- 17558373
TI  - Nosocomial meningitis caused by Enterobacteriaceae: risk factors and outcome in
      18 cases in 1992-2007.
AB  - Nosocomial neuroinfections due to Enterobacteriaceae represented 9.5% in our
      cohort of 171 cases of paediatric meningitis within last 15 years. Commonest
      etiologic agents was E. coli - 9 (50%) followed by Klebsiella pneumoniae - 3
      (16,7%) and Enterobacter cloacae. Citrobacter freundii, Proteus mirabilis and
      Salmonella enteritidis (1 each). Commonest risk factors were neonatal age 13 -
      (72.2%), very low birth weight 5 (27.8%), craniocerebral trauma - 4 (22.2%) and
      neurosurgery - 5 (27.8%). All but 1 case were treated with antibiotics: 8 with
      III-rd and 3 with IV-th generation cephalosporins (ceftazidim, cefotaxim and
      cefepim) 2 with meropenem and 4 with ciprofloxacin: Nosocomial meningitis due to
      enterobacteriaceae was associated with significantly high mortality (29.9% vs.
      15.1% in all cohort of pediatric meningitis - p<0.02).

PMID- 17558374
TI  - Nosocomial meningitis in neonates caused by Streptococcus agalactiae.
AB  - Streptococcus agalactiae is a rare cause of neonatal meningitis in the era of
      peripartum prophylaxis with prophylaxis with ampicillin in colonized/infected
      mothers. However 5 cases of meningitis among 171 cases of pediatric nosocomial
      meningitis database within last 15 years occurred. All 5 children were neonates
      (one VLBW and early gestation newborn), 2 after neurosurgery. All 5 cases were
      successfully cured with a combination of cefotaxim (or ceftazidim) plus
      aminoglycosides, in one case also with addition of vancomycin or ampicillin.
      However 3 of 5 cured patients had neurologic sequellae, two of them reversible
      hydrocephalus and in speech retardation.

PMID- 17558375
TI  - Neuroinfections due to Enterococcus faecalis in children.
AB  - Enterococcal meningitis is a rare complication of neurosurgical procedure or high
      technology treatment of children and occurs mainly imunocompromised neonates with
      very low birth weight, severe prematurity and complicates sometime
      ventriculoperitoneal shunt insertion or perinatal trauma. E. faecalis caused 10
      nosocomial meningitis and all strains were susceptible to vancomycin and
      chloramphenicol, and in our database 90% also to gentamicin and ampicillin.
      Mortality in our group of 10 children was 20% what is insignificantly higher than
      overall mortality in the whole cohort of meningitis within last 15 years in our
      database (15.1%). Early empiric therapy should include also ampicillin or
      vancomycin, if enterococcal etiology is suspected.

PMID- 17558376
TI  - Nosocomial meningitis caused by Staphylococcus other than S. aureus in children:
      multicentre study.
AB  - Analysing 101 cases of nosocomial meningitis due to staphylococci other than S.
      aureus within last 15 years, coagulase negative staphylococci represented the
      commonest pathogen. Major risk factor for staphylococcal meningitis was prior
      neurosurgery, mainly ventriculoperitoneal shunt insertion. Ten of 101 cases were
      caused by glycopeptide intermediate resistant strains in patients pretreated with
      multiple combination of antibiotics including vancomycin and shunt exchanges: 76%
      of strains were also oxacillin resistant.

PMID- 17558377
TI  - Neuroinfections complicating foreign body implants after perinatal trauma or
      meningitis in 60 children.
AB  - Meningitis after artificial implants in 60 children, mainly after foreign body
      infections (FBI) was caused more frequently by coagulase negative staphylococci
      and Ps. aeruginosa than other organisms and was significantly associated with
      perinatal trauma, hydrocephalus, haemorrhage or VLBW and had more neurologic
      sequels despite mortality was similar to other nosocomial meningitis.

PMID- 17558378
TI  - Neuroinfections and antimicrobials: do we need new molecules or new strategies?
AB  - Within last 15 years, analyzing patterns of etiology and resistance in organisms
      causing neuroinfections, emergence of resistance has been observed in Slovakia in
      S. haemolyticus to teicoplanin (11%), Ps. aeruginosa and A. baumannii to
      meropenem (20%) and Candida spp. (non-albicans Candida spp.) to fluconazol (20%).
      There are no new antibiotics against carbapenem resistant Ps. aeruginosa and
      Acinetobacter baumannii.

PMID- 17558379
TI  - Infectious diseases in disaster areas/catastrophes.
AB  - There is very little data and no prospective research possible in the field of
      catastrophic medicine (disaster medicine) including infectious diseases. This
      minireview tries to contribute to the pathogenesis and outcome of infectious
      diseases in areas after anthropogenic (war, genocide, terrorist attack,
      industrial disasters) and non anthropogenic (natural) catastrophes (earthquake,
      floods, tsunamis, hurricanes, volcano eruptions). Therefore ISC received a
      proposal to create a working group on infectious diseases in areas after
      catastrophes, better to understand epidemiology, prevention and therapy of
      infectious diseases occurring in conjunction to various anthropogenic and non
      anthropogenic (natural) disasters.

PMID- 17558380
TI  - Meningococcal meningitis among displaced and refugee camps in southern Sudan.

PMID- 17558381
TI  - Cerebral malaria in children in South Sudan: 8 years experience in 261 cases.
AB  - Two hundred-sixty-one (261) cases of cerebral malaria within last 8 years from 3
      tropical clinics in South Sudan were analyzed. Coma was present at 79.8% and
      convulsions at 25.6%. However 90.5% of children were cured. Commonest
      antimalarial drugs used were intravenous quinine, clindamycin, artesunate and
      artemeter.

PMID- 17558382
TI  - Infectious embolisation to the central nervous system from endocarditis: analyses
      of 99 cases.
AB  - Within a cohort of 606 cases of infective endocarditis, 263 were complicated and
      99 embolizing, of them 32 to the central nervous system (CNS). Significant
      predictors of CNS embolisation were inappropriate therapy (p<0.01) and
      enterococcal etiology (p<0.01). Mortality in patients with CNS emboli was 65%
      what was significantly higher than in cases without embolisation - 15% (p<0.01).

PMID- 17558383
TI  - Ten years experience with 497 cases of neuroinfections in tropic: in limited
      laboratory infrastructure initially treat both, cerebral malaria and meningitis.
AB  - Review of 497 cases of neuroinfections in 7 tropical clinics in Ethiopia, Uganda,
      Burundi, Kenya, Sudan within 2000-2007 was performed. 97.5% of all cases was
      cerebral malaria (40.1%) and bacterial meningitis (56.4%). TB meningitis,
      cerebral cryptococcosis and sleeping sickness were very rare.

PMID- 17558384
TI  - Higher-order wavefront aberration and letter-contrast sensitivity in keratoconus.
AB  - AIMS: To evaluate the relation between higher-order aberration of the eye and
      contrast sensitivity function in eyes with keratoconus. METHODS: In 22 eyes of 14
      patients with keratoconus (age 30.5+/-8.4 years, means+/-SD) and 26 eyes of 13
      normal controls (age 29.2+/-6.7 years), ocular higher-order wavefront aberration
      for a 6-mm pupil was measured with the Hartmann-Schack aberrometer (KR-9000 PW,
      Topcon). The root mean square (RMS) of third- and fourth-order Zernike
      coefficients was used to represent higher-order aberrations. The letter-contrast
      sensitivity was examined using the CSV-1000LV contrast chart (Vector Vision).
      RESULTS: In the keratoconus group, the letter-contrast sensitivity showed
      significant correlation with third-order (Spearman's correlation coefficient r=
      0.736, P<0.001) and fourth-order aberrations (r=-0.464, P<0.05). There was
      borderline correlation between log MAR BSCVA and third-order (r=0.413, P=0.070)
      and fourth-order aberrations (r=0.394, P=0.086). In the normal group, the letter
      contrast sensitivity had no significant correlation with third-order (r=-0.170,
      P=0.411) and fourth-order aberrations (r=-0.088, P=0.673), and log MAR best
      spectacle-corrected visual acuity (BSCVA) showed no correlation with third-order
      (r=0.063, P=0.762) and fourth-order aberrations (r=-0.282, P=0.165). CONCLUSIONS:
      In eyes with keratoconus, there is significant correlation between contrast
      sensitivity and ocular higher-order wavefront aberrations.

PMID- 17558385
TI  - Ocular surface changes in limbal stem cell deficiency caused by chemical injury:
      a histologic study of excised pannus from recipients of cultured corneal
      epithelium.
AB  - PURPOSE: To report histopathologic changes of the ocular surface pannus in
      patients with severe limbal stem cell deficiency (LSCD). METHODS: Corneal and
      conjunctival pannus tissues from 29 patients undergoing ocular reconstruction
      with cultured limbal cell transplantation were included. The medical records of
      these patients were reviewed for demographics, aetiologic diagnosis, type of
      injury, interval between the initial insult and excision of pannus, and medical
      history involving human amniotic membrane (HAM) or limbal transplantation. The
      paraffin-embedded tissues were reviewed for epithelial changes, type-degree of
      fibrosis, degenerative changes, vascular changes, conjunctivalization of corneal
      surface, and evidence of residual HAM. We attempted a clinicopathologic
      correlation to understand the pathogenesis of pannus formation in LSCD. RESULTS:
      The 29 tissues were from 29 eyes of patients with primary aetiology of chemical
      burn in 89.6% (undetermined in 10.4%) of cases. The pannus showed epithelial
      hyperplasia in 62%, active fibrosis in 66%, severe inflammation in 21%, giant
      cell reaction in 28%, and stromal calcification in 14% cases. Goblet cells were
      seen over the cornea in 64% cases; their absence was associated with squamous
      metaplasia of the conjunctiva and with long duration of insult. Evidence of
      residual HAM was noted in 42% cases. CONCLUSIONS: The commonest cause of severe
      LSCD is alkali-induced injury. Goblet cells over the cornea were seen in 60% of
      cases. HAM used for ocular surface reconstruction could persist for long periods
      within the corneal pannus, thus raising the need for further studies with long
      term follow-up.

PMID- 17558386
TI  - Plain X-ray and computed tomography of the orbit in cases and suspected cases of
      intraocular foreign body.
AB  - AIM: To evaluate the roles of plain X-ray and computed tomography (CT) orbital
      imaging in cases and suspected cases of intraocular foreign body (IOFB). METHODS:
      Retrospective review of clinical and radiological data relating to 204
      consecutive cases and suspected cases of IOFB.SettingRoyal Victoria Eye and Ear
      Hospital, Dublin, Ireland. RESULTS: Plain X-rays were performed in the absence of
      clinically evident ocular penetration in 177 (87%) cases, and no IOFB was
      demonstrated in any of these radiographs. Twenty-seven (13%) plain X-ray
      radiographs were obtained in the presence of clinically evident ocular
      penetration, and an IOFB was clinically visible in 19 (70%) of these cases. CT
      scans were undertaken in 21 (10%) of the 204 patients. Of these CT images, 9
      (43%) and 12 (57%) were undertaken in the absence and presence of clinically
      evident ocular penetration, respectively. None (0%) and all (100%) of the CT
      scans obtained in the absence and presence of clinically evident ocular
      penetration demonstrated an IOFB, respectively. CONCLUSION: Plain X-ray and CT
      orbital imaging are non-contributory in the absence of clinically evident ocular
      penetration. In the presence of clinically evident ocular penetration, and where
      an IOFB is clinically visible, plain X-ray orbital radiography may have a role in
      excluding multiple IOFBs. In the presence of clinically evident ocular
      penetration, but where an IOFB is not clinically visible, CT orbital imaging
      remains the investigation of choice, and the role of pre-CT plain X-ray orbital
      radiography, as recommended by the guidelines of the Royal College of
      Radiologists, merits re-evaluation.

PMID- 17558387
TI  - Genome-wide profiles of STAT1 DNA association using chromatin immunoprecipitation
      and massively parallel sequencing.
AB  - We developed a method, ChIP-sequencing (ChIP-seq), combining chromatin
      immunoprecipitation (ChIP) and massively parallel sequencing to identify
      mammalian DNA sequences bound by transcription factors in vivo. We used ChIP-seq
      to map STAT1 targets in interferon-gamma (IFN-gamma)-stimulated and unstimulated
      human HeLa S3 cells, and compared the method's performance to ChIP-PCR and to
      ChIP-chip for four chromosomes. By ChIP-seq, using 15.1 and 12.9 million uniquely
      mapped sequence reads, and an estimated false discovery rate of less than 0.001,
      we identified 41,582 and 11,004 putative STAT1-binding regions in stimulated and
      unstimulated cells, respectively. Of the 34 loci known to contain STAT1
      interferon-responsive binding sites, ChIP-seq found 24 (71%). ChIP-seq targets
      were enriched in sequences similar to known STAT1 binding motifs. Comparisons
      with two ChIP-PCR data sets suggested that ChIP-seq sensitivity was between 70%
      and 92% and specificity was at least 95%.

PMID- 17558391
TI  - 'Rejuvenation' protects neurons in mouse models of Parkinson's disease.
AB  - Why dopamine-containing neurons of the brain's substantia nigra pars compacta die
      in Parkinson's disease has been an enduring mystery. Our studies suggest that the
      unusual reliance of these neurons on L-type Ca(v)1.3 Ca2+ channels to drive their
      maintained, rhythmic pacemaking renders them vulnerable to stressors thought to
      contribute to disease progression. The reliance on these channels increases with
      age, as juvenile dopamine-containing neurons in the substantia nigra pars
      compacta use pacemaking mechanisms common to neurons not affected in Parkinson's
      disease. These mechanisms remain latent in adulthood, and blocking Ca(v)1.3 Ca2+
      channels in adult neurons induces a reversion to the juvenile form of pacemaking.
      Such blocking ('rejuvenation') protects these neurons in both in vitro and in
      vivo models of Parkinson's disease, pointing to a new strategy that could slow or
      stop the progression of the disease.

PMID- 17558392
TI  - Wurst is essential for airway clearance and respiratory-tube size control.
AB  - The Drosophila melanogaster tracheal system and the mammalian lung are branching
      networks of tubular epithelia that convert during late embryogenesis from liquid-
      to air-filling. Little is known about how respiratory-tube size and physiology
      are coordinated. Here, we show that the Drosophila wurst gene encodes a unique J
      domain transmembrane protein highly conserved in metazoa. In wurst mutants,
      respiratory-tube length is increased and lumen clearance is abolished, preventing
      gas filling of the airways. Wurst is essential for clathrin-mediated endocytosis,
      which is required for size determination and lumen clearance of the airways.
      wurst recruits heat shock cognate protein 70-4 and clathrin to the apical
      membrane of epithelial cells. The sequence conservation of the single Wurst
      orthologues in mice and humans offer new opportunities for genetic studies of
      clinically relevant lung syndromes caused by the failure of liquid clearance and
      respiratory-tube size control.

PMID- 17558393
TI  - Wnt signalling regulates paxillin ubiquitination essential for mesodermal cell
      motility.
AB  - Gastrulation movements are critical for establishing the three germ layers and
      the architecture of vertebrate embryos. During Xenopus laevis gastrulation,
      mesodermal tissue migrates on the blastocoel roof and elongates along the antero
      posterior axis. During this process, cells in the dorsal mesoderm are polarized
      and intercalate with each other, which is defined as convergent extension and is
      known to be regulated by the non-canonical Wnt pathway. Here, we show that
      paxillin plays an essential role in this process. Paxillin is a focal-adhesion
      associated protein implicated in the regulation of actin cytoskeletal
      organization and cell motility, but its role in Xenopus embryogenesis has not yet
      been clarified. We demonstrate that the Wnt pathway controls the ubiquitination
      and stability of paxillin, and that this regulatory mechanism is essential for
      convergent extension movements. We identified a RING finger protein XRNF185,
      which physically binds to paxillin and the proteasome. XRNF185 destabilizes
      paxillin at focal adhesions and promotes mesodermal cell migration during
      convergent extension. We propose a mechanism to regulate gastrulation movements
      that involves paxillin ubiquitination and stability controlled by Wnt signalling.

PMID- 17558394
TI  - Maximal chromosome compaction occurs by axial shortening in anaphase and depends
      on Aurora kinase.
AB  - Eukaryotic cells must first compact their chromosomes before faithfully
      segregating them during cell division. Failure to do so can lead to segregation
      defects with pathological consequences, such as aneuploidy and cancer. Duplicated
      interphase chromosomes are, therefore, reorganized into tight rods before being
      separated and directed to the newly forming daughter cells. This vital
      reorganization of chromatin remains poorly understood. To address the dynamics of
      mitotic condensation of single chromosomes in intact cells, we developed
      quantitative assays based on confocal time-lapse microscopy of live mammalian
      cells stably expressing fluorescently tagged core histones. Surprisingly, maximal
      compaction was not reached in metaphase, but in late anaphase, after sister
      chromatid segregation. We show that anaphase compaction proceeds by a mechanism
      of axial shortening of the chromatid arms from telomere to centromere. Chromatid
      axial shortening was not affected in condensin-depleted cells, but depended
      instead on dynamic microtubules and Aurora kinase. Acute perturbation of this
      compaction resulted in failure to rescue segregation defects and in multilobed
      daughter nuclei, suggesting functions in chromosome segregation and nuclear
      architecture.

PMID- 17558395
TI  - Threonine phosphorylation post-translationally regulates protein secretion in
      Pseudomonas aeruginosa.
AB  - Secreted proteins are crucial to the arsenal of bacterial pathogens. Although
      optimal activity of these proteins is likely to require precise regulation of
      release, the signalling events that trigger secretion are poorly understood.
      Here, we identify a threonine phosphorylation event that post-translationally
      regulates the Hcp secretion island-I-encoded type VI secretion system of
      Pseudomonas aeruginosa (H-T6SS). We show that a serine-threonine kinase, PpkA, is
      required for assembly of the H-T6SS and for secretion of Hcp1. PpkA activity is
      antagonized by PppA, a Ser-Thr phosphatase. These proteins exhibit reciprocal
      effects on the H-T6SS by acting on an FHA domain-containing protein, termed Fha1.
      Colocalization experiments with the T6S AAA+ family protein, ClpV1, indicate that
      Fha1 is a core scaffolding protein of the H-T6SS. Mutations affecting this H-T6S
      regulatory pathway provide a molecular explanation for the variation in Hcp1
      secretion among clinical P. aeruginosa isolates. This mechanism of triggering
      secretion may be general, as many T6SSs contain orthologues of these proteins.
      Post-translational regulation of protein secretion by Thr phosphorylation is
      unprecedented in bacteria, and is likely to reflect the requirement for T6S to
      respond rapidly and reversibly to its environment.

PMID- 17558396
TI  - Dishevelled promotes axon differentiation by regulating atypical protein kinase
      C.
AB  - The atypical protein kinase C (aPKC) in complex with PAR3 and PAR6 is required
      for axon-dendrite differentiation, but the upstream factors responsible for
      regulating its activity are largely unknown. Here, we report that in cultured
      hippocampal neurons aPKC is directly regulated by Dishevelled (Dvl), an immediate
      downstream effector of Wnt. We found that downregulation of Dvl abrogated axon
      differentiation, whereas Dvl overexpression resulted in multiple axon formation.
      Interestingly, Dvl was associated with aPKC and this interaction resulted in aPKC
      stabilization and activation. Furthermore, the multiple axon formation resulting
      from Dvl overexpression was attenuated by expressing a dominant-negative aPKC in
      these neurons and overexpression of aPKC prevented the loss of axon caused by Dvl
      downregulation. Finally, Wnt5a, a noncanonical Wnt, activated aPKC and promoted
      axon differentiation. The Wnt5a effect on axon differentiation was attenuated by
      downregulating Dvl or inhibiting aPKC. Thus, Dvl-aPKC interaction can promote
      axon differentiation mediated by the PAR3-PAR6-aPKC complex.

PMID- 17558397
TI  - The ubiquitin-specific protease USP28 is required for MYC stability.
AB  - The MYC proto-oncogene encodes a transcription factor that has been implicated in
      the genesis of many human tumours. Here, we used a bar-code short hairpin RNA
      (shRNA) screen to identify multiple genes that are required for MYC function. One
      of these genes encodes USP28, an ubiquitin-specific protease. USP28 is required
      for MYC stability in human tumour cells. USP28 binds to MYC through an
      interaction with FBW7alpha, an F-box protein that is part of an SCF-type
      ubiquitin ligase. Therefore, it stabilizes MYC in the nucleus, but not in the
      nucleolus, where MYC is degraded by FBW7gamma. High expression levels of USP28
      are found in colon and breast carcinomas, and stabilization of MYC by USP28 is
      essential for tumour-cell proliferation.

PMID- 17558398
TI  - Small-molecule pheromones that control dauer development in Caenorhabditis
      elegans.
AB  - In response to high population density or low food supply, the nematode
      Caenorhabditis elegans enters an alternative larval stage, known as the dauer,
      that can withstand adverse conditions for prolonged periods. C. elegans senses
      its population density through a small-molecule signal, traditionally called the
      dauer pheromone, that it secretes into its surroundings. Here we show that the
      dauer pheromone consists of several structurally related ascarosides-derivatives
      of the dideoxysugar ascarylose-and that two of these ascarosides (1 and 2) are
      roughly two orders of magnitude more potent at inducing dauer formation than a
      previously reported dauer pheromone component (3) and constitute a
      physiologically relevant signal. The identification of dauer pheromone components
      1 and 2 will facilitate the identification of target receptors and downstream
      signaling proteins.

PMID- 17558399
TI  - RECK modulates Notch signaling during cortical neurogenesis by regulating ADAM10
      activity.
AB  - We report that during cortical development in the mouse embryo, reversion
      inducing cysteine-rich protein with Kazal motifs (RECK) critically regulates
      Notch signaling by antagonizing the ectodomain shedding of Notch ligands, which
      is mediated by a disintegrin and metalloproteinase domain 10 (ADAM10). In the
      embryonic brain, RECK is specifically expressed in Nestin-positive neural
      precursor cells (NPCs). Reck-deficient NPCs undergo precocious differentiation
      that is associated with downregulated Nestin expression, impaired Notch signaling
      and defective self-renewal. These phenotypes were substantially rescued either by
      enhancing Notch signaling or by suppressing endogenous ADAM10 activity.
      Consequently, we found that RECK regulates the ectodomain shedding of Notch
      ligands by directly inhibiting the proteolytic activity of ADAM10. This mechanism
      appeared to be essential for Notch ligands to properly induce Notch signaling in
      neighboring cells. These findings indicate that RECK is a physiological inhibitor
      of ADAM10, an upstream regulator of Notch signaling and a critical modulator of
      brain development.

PMID- 17558400
TI  - Regulation of T-type calcium channels by Rho-associated kinase.
AB  - We investigated the regulation of T-type channels by Rho-associated kinase
      (ROCK). Activation of ROCK via the endogenous ligand lysophosphatidic acid (LPA)
      reversibly inhibited the peak current amplitudes of rat Ca(v)3.1 and Ca(v)3.3
      channels without affecting the voltage dependence of activation or inactivation,
      whereas Ca(v)3.2 currents showed depolarizing shifts in these parameters. LPA
      induced inhibition of Ca(v)3.1 was dependent on intracellular GTP, and was
      antagonized by treatment with ROCK and RhoA inhibitors, LPA receptor antagonists
      or GDPssS. Site-directed mutagenesis of the Ca(v)3.1 alpha1 subunit revealed that
      the ROCK-mediated effects involve two distinct phosphorylation consensus sites in
      the domain II-III linker. ROCK activation by LPA reduced native T-type currents
      in Y79 retinoblastoma and in lateral habenular neurons, and upregulated native
      Ca(v)3.2 current in dorsal root ganglion neurons. Our data suggest that ROCK is
      an important regulator of T-type calcium channels, with potentially far-reaching
      implications for multiple cell functions modulated by LPA.

PMID- 17558401
TI  - UNC-46 is required for trafficking of the vesicular GABA transporter.
AB  - Mutations in unc-46 in Caenorhabditis elegans cause defects in all behaviors that
      are mediated by GABA. Here we show that UNC-46 is a sorting factor that localizes
      the vesicular GABA transporter to synaptic vesicles. The UNC-46 protein is
      related to the LAMP (lysosomal associated membrane protein) family of proteins
      and is localized at synapses. In unc-46 mutants, the vesicular transporter is not
      found specifically in synaptic vesicles but rather is diffusely spread along the
      axon. Mislocalization of the transporter severely reduces the frequency of
      miniature currents, but the remaining currents are normal in amplitude. Because
      the number of synaptic vesicles is not depleted, it is likely that only a
      fraction of vesicles harbor the transporter in unc-46 mutants. Our data indicate
      that the transporter and UNC-46 have mutual roles in sorting. The vesicular GABA
      transporter recruits UNC-46 to synaptic vesicle precursors in the cell body, and
      UNC-46 sorts the transporter at the cell body and during endocytosis at the
      synapse.

PMID- 17558402
TI  - Suppression of conditioning to ambiguous cues by pharmacogenetic inhibition of
      the dentate gyrus.
AB  - Serotonin receptor 1A knockout (Htr1a(KO)) mice show increased anxiety-related
      behavior in tests measuring innate avoidance. Here we demonstrate that Htr1a(KO)
      mice show enhanced fear conditioning to ambiguous conditioned stimuli, a hallmark
      of human anxiety. To examine the involvement of specific forebrain circuits in
      this phenotype, we developed a pharmacogenetic technique for the rapid tissue-
      and cell type-specific silencing of neural activity in vivo. Inhibition of
      neurons in the central nucleus of the amygdala suppressed conditioned responses
      to both ambiguous and nonambiguous cues. In contrast, inhibition of hippocampal
      dentate gyrus granule cells selectively suppressed conditioned responses to
      ambiguous cues and reversed the knockout phenotype. These data demonstrate that
      Htr1a(KO) mice have a bias in the processing of threatening cues that is
      moderated by hippocampal mossy-fiber circuits, and suggest that the hippocampus
      is important in the response to ambiguous aversive stimuli.

PMID- 17558403
TI  - Decreased demands on cognitive control reveal the neural processing benefits of
      forgetting.
AB  - Remembering often requires the selection of goal-relevant memories in the face of
      competition from irrelevant memories. Although there is a cost of selecting
      target memories over competing memories (increased forgetting of the competing
      memories), here we report neural evidence for the adaptive benefits of forgetting
      -namely, reduced demands on cognitive control during future acts of remembering.
      Functional magnetic resonance imaging during selective retrieval showed that
      repeated retrieval of target memories was accompanied by dynamic reductions in
      the engagement of functionally coupled cognitive control mechanisms that detect
      (anterior cingulate cortex) and resolve (dorsolateral and ventrolateral
      prefrontal cortex) mnemonic competition. Strikingly, regression analyses revealed
      that this prefrontal disengagement tracked the extent to which competing memories
      were forgotten; greater forgetting of competing memories was associated with a
      greater decline in demands on prefrontal cortex during target remembering. These
      findings indicate that, although forgetting can be frustrating, memory might be
      adaptive because forgetting confers neural processing benefits.

PMID- 17558404
TI  - Cannabinoids mediate analgesia largely via peripheral type 1 cannabinoid
      receptors in nociceptors.
AB  - Although endocannabinoids constitute one of the first lines of defense against
      pain, the anatomical locus and the precise receptor mechanisms underlying
      cannabinergic modulation of pain are uncertain. Clinical exploitation of the
      system is severely hindered by the cognitive deficits, memory impairment, motor
      disturbances and psychotropic effects resulting from the central actions of
      cannabinoids. We deleted the type 1 cannabinoid receptor (CB1) specifically in
      nociceptive neurons localized in the peripheral nervous system of mice,
      preserving its expression in the CNS, and analyzed these genetically modified
      mice in preclinical models of inflammatory and neuropathic pain. The nociceptor
      specific loss of CB1 substantially reduced the analgesia produced by local and
      systemic, but not intrathecal, delivery of cannabinoids. We conclude that the
      contribution of CB1-type receptors expressed on the peripheral terminals of
      nociceptors to cannabinoid-induced analgesia is paramount, which should enable
      the development of peripherally acting CB1 analgesic agonists without any central
      side effects.

PMID- 17558405
TI  - A central role for Necl4 (SynCAM4) in Schwann cell-axon interaction and
      myelination.
AB  - Myelination in the peripheral nervous system requires close contact between
      Schwann cells and the axon, but the underlying molecular basis remains largely
      unknown. Here we show that cell adhesion molecules (CAMs) of the nectin-like
      (Necl, also known as SynCAM or Cadm) family mediate Schwann cell-axon interaction
      during myelination. Necl4 is the main Necl expressed by myelinating Schwann cells
      and is located along the internodes in direct apposition to Necl1, which is
      localized on axons. Necl4 serves as the glial binding partner for axonal Necl1,
      and the interaction between these two CAMs mediates Schwann cell adhesion. The
      disruption of the interaction between Necl1 and Necl4 by their soluble
      extracellular domains, or the expression of a dominant-negative Necl4 in Schwann
      cells, inhibits myelination. These results suggest that Necl proteins are
      important for mediating axon-glia contact during myelination in peripheral
      nerves.

PMID- 17558406
TI  - Intra- and intercellular RNA interference in Arabidopsis thaliana requires
      components of the microRNA and heterochromatic silencing pathways.
AB  - In RNA interference (RNAi), double-stranded RNA (dsRNA) is processed into short
      interfering RNA (siRNA) to mediate sequence-specific gene knockdown. The genetics
      of plant RNAi is not understood, nor are the bases for its spreading between
      cells. Here, we unravel the requirements for biogenesis and action of siRNAs
      directing RNAi in Arabidopsis thaliana and show how alternative routes
      redundantly mediate this process under extreme dsRNA dosages. We found that SMD1
      and SMD2, required for intercellular but not intracellular RNAi, are allelic to
      RDR2 and NRPD1a, respectively, previously implicated in siRNA-directed
      heterochromatin formation through the action of DCL3 and AGO4. However, neither
      DCL3 nor AGO4 is required for non-cell autonomous RNAi, uncovering a new pathway
      for RNAi spreading or detection in recipient cells. Finally, we show that the
      genetics of RNAi is distinct from that of antiviral silencing and propose that
      this experimental silencing pathway has a direct endogenous plant counterpart.

PMID- 17558407
TI  - Mutations in the gene encoding the basal body protein RPGRIP1L, a nephrocystin-4
      interactor, cause Joubert syndrome.
AB  - Protein-protein interaction analyses have uncovered a ciliary and basal body
      protein network that, when disrupted, can result in nephronophthisis (NPHP),
      Leber congenital amaurosis, Senior-Loken syndrome (SLSN) or Joubert syndrome
      (JBTS). However, details of the molecular mechanisms underlying these disorders
      remain poorly understood. RPGRIP1-like protein (RPGRIP1L) is a homolog of RPGRIP1
      (RPGR-interacting protein 1), a ciliary protein defective in Leber congenital
      amaurosis. We show that RPGRIP1L interacts with nephrocystin-4 and that mutations
      in the gene encoding nephrocystin-4 (NPHP4) that are known to cause SLSN disrupt
      this interaction. RPGRIP1L is ubiquitously expressed, and its protein product
      localizes to basal bodies. Therefore, we analyzed RPGRIP1L as a candidate gene
      for JBTS and identified loss-of-function mutations in three families with typical
      JBTS, including the characteristic mid-hindbrain malformation. This work
      identifies RPGRIP1L as a gene responsible for JBTS and establishes a central role
      for cilia and basal bodies in the pathophysiology of this disorder.

PMID- 17558408
TI  - A genome-wide association study for celiac disease identifies risk variants in
      the region harboring IL2 and IL21.
AB  - We tested 310,605 SNPs for association in 778 individuals with celiac disease and
      1,422 controls. Outside the HLA region, the most significant finding (rs13119723;
      P = 2.0 x 10(-7)) was in the KIAA1109-TENR-IL2-IL21 linkage disequilibrium block.
      We independently confirmed association in two further collections (strongest
      association at rs6822844, 24 kb 5' of IL21; meta-analysis P = 1.3 x 10(-14), odds
      ratio = 0.63), suggesting that genetic variation in this region predisposes to
      celiac disease.

PMID- 17558409
TI  - The ciliary gene RPGRIP1L is mutated in cerebello-oculo-renal syndrome (Joubert
      syndrome type B) and Meckel syndrome.
AB  - Cerebello-oculo-renal syndrome (CORS), also called Joubert syndrome type B, and
      Meckel (MKS) syndrome belong to the group of developmental autosomal recessive
      disorders that are associated with primary cilium dysfunction. Using SNP mapping,
      we identified missense and truncating mutations in RPGRIP1L (KIAA1005) in both
      CORS and MKS, and we show that inactivation of the mouse ortholog Rpgrip1l (Ftm)
      recapitulates the cerebral, renal and hepatic defects of CORS and MKS. In
      addition, we show that RPGRIP1L colocalizes at the basal body and centrosomes
      with the protein products of both NPHP6 and NPHP4, known genes associated with
      MKS, CORS and nephronophthisis (a related renal disorder and ciliopathy). In
      addition, the RPGRIP1L missense mutations found in CORS individuals diminishes
      the interaction between RPGRIP1L and nephrocystin-4. Our findings show that
      mutations in RPGRIP1L can cause the multiorgan phenotypic abnormalities found in
      CORS or MKS, which therefore represent a continuum of the same underlying
      disorder.

PMID- 17558410
TI  - Bcl-6 mediates the germinal center B cell phenotype and lymphomagenesis through
      transcriptional repression of the DNA-damage sensor ATR.
AB  - Antibody specificity and diversity is generated in B cells during germinal center
      maturation through clonal expansion while they undergo class-switch recombination
      and somatic hypermutation. Here we demonstrate that the transcriptional repressor
      Bcl-6 mediates this phenotype by directly repressing ATR in centroblasts and
      lymphoma cells. ATR is critical in replication and DNA damage-sensing
      checkpoints. Bcl-6 allowed B cells to evade ATR-mediated checkpoints and
      attenuated the response of the B cells to exogenous DNA damage. Repression of ATR
      was necessary and sufficient for those Bcl-6 activities. CD40 signaling 'rescued'
      B cells from those effects by disrupting the Bcl-6 transcription-repression
      complex on the promoter of the gene encoding ATR. Our data demonstrate a
      transcriptional regulatory loop whereby Bcl-6 mediates the centroblast phenotype
      through transient silencing of ATR.

PMID- 17558411
TI  - IgEb immune complexes activate macrophages through FcgammaRIV binding.
AB  - Because functional analysis of Fc receptors (FcRs) relies heavily on mouse
      models, the identification of another Fcgamma receptor is particularly
      noteworthy. We demonstrate that FcgammaRIV, identified here as the mouse ortholog
      of primate FcgammaRIII, required association of the FcR gamma-chain for optimal
      expression and function on myeloid cells; its signaling potential was also
      enhanced by a cytoplasmic 'YEEP' motif that was able to recruit the adaptor
      molecule Crk-L and phosphatidylinositol-3-OH kinase. Unexpectedly, FcgammaRIV
      'preferentially' bound immunoglobulin E antibodies of the 'b' allotype (IgE(b))
      as well as IgG2a and IgG2b antibodies. Ligation of FcgammaRIV by antigen-IgE(b)
      immune complexes promoted macrophage-mediated phagocytosis, presentation of
      antigen to T cells, production of proinflammatory cytokines and the late phase of
      cutaneous allergic reactions. IgE(b) antibody-mediated modification of macrophage
      responses may therefore influence mouse asthma models and strain-dependent
      differences in parasite susceptibility.

PMID- 17558412
TI  - Recombinant RNA technology: the tRNA scaffold.
AB  - RNA has emerged as a major player in most cellular processes. Understanding these
      processes at the molecular level requires homogeneous RNA samples for structural,
      biochemical and pharmacological studies. So far, this has been a bottleneck, as
      the only methods for producing such pure RNA have been in vitro syntheses. Here
      we describe a generic approach for expressing and purifying structured RNA in
      Escherichia coli, using tools that parallel those available for recombinant
      proteins. Our system is based on a camouflage strategy, the 'tRNA scaffold', in
      which the recombinant RNA is disguised as a natural RNA and thus hijacks the host
      machinery, escaping cellular RNases. This opens the way to large-scale structural
      and molecular investigations of RNA function.

PMID- 17558413
TI  - Determination of the sites of tyrosine O-sulfation in peptides and proteins.
AB  - Tyrosine O-sulfation is a key post-translational modification that regulates
      protein-protein interactions in extracellular space. We describe a subtractive
      strategy to determine the sites of tyrosine O-sulfation in proteins. Hydroxyl
      groups on unsulfated tyrosines are blocked by stoichiometric acetylation in a one
      step reaction using sulfosuccinimidyl acetate (S-NHSAc) in the presence of
      imidazole at pH 7.0. The presence of sulfotyrosine is indicated by the detection
      of free tyrosine after tandem mass spectrometry (MS/MS) analysis under conditions
      in which the sulfuryl group of sulfotyrosine is labile. Since phosphorylation and
      sulfation of tyrosine are isobaric, we used alkaline phosphatase treatment to
      distinguish these two modifications. Using this methodology we identified the
      sites and the order of sulfation of several peptides mediated by purified human
      tyrosylprotein sulfotransferases (TPSTs), and unambiguously determined the
      tyrosine sulfation sites in mouse lumican and human vitronectin.

PMID- 17558414
TI  - Imaging axonal transport of mitochondria in vivo.
AB  - Neuronal mitochondria regulate synaptic physiology and cellular survival, and
      disruption of their function or transport causes neurological disease. We present
      a fluorescence method to selectively image mitochondrial dynamics in the mouse
      nervous system, in both live mice and acute explants. We show that axon damage
      and recovery lead to early and sustained changes in anterograde and retrograde
      transport. In vivo imaging of mitochondria will be a useful tool to analyze this
      essential organelle.

PMID- 17558415
TI  - Multifunctional TH1 cells define a correlate of vaccine-mediated protection
      against Leishmania major.
AB  - CD4+ T cells have a crucial role in mediating protection against a variety of
      pathogens through production of specific cytokines. However, substantial
      heterogeneity in CD4+ T-cell cytokine responses has limited the ability to define
      an immune correlate of protection after vaccination. Here, using multiparameter
      flow cytometry to assess the immune responses after immunization, we show that
      the degree of protection against Leishmania major infection in mice is predicted
      by the frequency of CD4+ T cells simultaneously producing interferon-gamma,
      interleukin-2 and tumor necrosis factor. Notably, multifunctional effector cells
      generated by all vaccines tested are unique in their capacity to produce high
      amounts of interferon-gamma. These data show that the quality of a CD4+ T-cell
      cytokine response can be a crucial determinant in whether a vaccine is
      protective, and may provide a new and useful prospective immune correlate of
      protection for vaccines based on T-helper type 1 (TH1) cells.

PMID- 17558416
TI  - The multifunctional RNA-binding protein hnRNP A1 is required for processing of
      miR-18a.
AB  - hnRNP A1 is an RNA-binding protein involved in various aspects of RNA processing.
      Use of an in vivo cross-linking and immunoprecipitation protocol to find hnRNP A1
      RNA targets resulted in the identification of a microRNA (miRNA) precursor, pre
      miR-18a. This microRNA is expressed as part of a cluster of intronic RNAs,
      including miR-17, miR-18a, miR-19a, miR-20a, miR-19b-1 and miR-92, and
      potentially acts as an oncogene. Here we show that hnRNP A1 binds specifically to
      the primary RNA sequence pri-miR-18a before Drosha processing. HeLa cells
      depleted of hnRNP A1 have reduced in vitro processing activity with pri-miR-18a
      and also show reduced abundances of endogenous pre-miR-18a. Furthermore, we show
      that hnRNP A1 is required for miR-18a-mediated repression of a target reporter in
      vivo. These results underscore a previously uncharacterized role for general RNA
      binding proteins as auxiliary factors that facilitate the processing of specific
      miRNAs.

PMID- 17558417
TI  - Structural basis for DNA duplex separation by a superfamily-2 helicase.
AB  - To reveal the mechanism of processive strand separation by superfamily-2 (SF2) 3'
      ->5' helicases, we determined apo and DNA-bound crystal structures of archaeal
      Hel308, a helicase that unwinds lagging strands and is related to human DNA
      polymerase theta. Our structure captures the duplex-unwinding reaction, shows
      that initial strand separation does not require ATP and identifies a prominent
      beta-hairpin loop as the unwinding element. Similar loops in hepatitis C virus
      NS3 helicase and RNA-decay factors support the idea that this duplex-unwinding
      mechanism is applicable to a broad subset of SF2 helicases. Comparison with ATP
      bound SF2 enzymes suggests that ATP promotes processive unwinding of 1 base pair
      by ratchet-like transport of the 3' product strand. Our results provide a first
      structural framework for strand separation by processive SF2 3'-->5' helicases
      and reveal important mechanistic differences from SF1 helicases.

PMID- 17558418
TI  - Global proteomic analysis distinguishes biologic differences in head and neck
      squamous carcinoma.
AB  - The goal of this study was to establish a method for detecting biologically
      significant differences in protein expression of head and neck squamous cell
      carcinoma (HNSCC) obtained from the same samples utilized in gene expression
      analyses. Proteins from two head and neck tumor cell lines, SCC-25 and FaDu, were
      isolated from the denatured protein solution remaining from the TRIzol extraction
      procedure used for isolation of total RNA for microarray analysis. Peptides
      resulting from chemical and enzymatic digestion of the proteins were first
      separated by strong cation-exchange chromatography, followed by liquid
      chromatography-mass spectrometry (LC-MS) analysis on a QqTOF mass spectrometer.
      Stable isotope-labeled synthetic peptides were added to each ion-exchange
      fraction as internal standards, for reversed-phase HPLC retention time alignment.
      Protein extraction and digestion were repeated three times for each cell line and
      each extract was analyzed three times by LC-MS. To discriminate between technical
      vs biological variation, the ion-exchange fraction, retention time, normalized
      mass and signal intensity of these nine data sets were constructed into numerical
      arrays for statistical analysis. Of the approximately 50,000 signals, 90 peptide
      ions were found to discriminate the two cell lines with high stringency. Of
      those, six peptides were derived from vimentin and four peptides were derived
      from annexin II; both expressed more in SCC-25. Follow-up analysis of some of
      these signals by LC-MS/MS and RNA expression profiling revealed both concordance
      and discordance of RNA and protein expression. This study demonstrates that this
      procedure is highly reliable for identifying peptides that distinguish biological
      variability among samples, indicating that this method can be applied to study
      clinical samples, to identify potential prognostic biomarkers for HNSCC.

PMID- 17558419
TI  - Getting it right: designing microarray (and not 'microawry') comparative genomic
      hybridization studies for cancer research.
AB  - The development of high-resolution microarray-based comparative genomic
      hybridization (aCGH), using cDNA, bacterial artificial chromosome (BAC) and
      oligonucleotide probes, is providing tremendous opportunities for translational
      research by facilitating detailed analysis of entire cancer genomes in a single
      experiment. However, this technology will only fulfil its promise if studies
      incorporating aCGH are designed with a full understanding of its current
      limitations and the strategies available to circumvent them. While there have
      been several excellent reviews on the current status of this technology, there is
      currently very little guidance available regarding the appropriate design of
      experiments incorporating aCGH (including the strengths and weaknesses of each
      platform), and how best to combine the results obtained from aCGH with other
      'omic' technologies, including gene expression. In this review, we present the
      key design issues that need to be considered in order to optimize aCGH studies,
      including sample selection, the definition of appropriate experimental
      objectives, arguments for and against the various microarray platforms that are
      currently available, and methods for data validation and integration. It is
      envisaged that future well-designed aCGH studies will enhance our understanding
      of the genetic basis of cancer, and lead to the identification of novel
      predictive and prognostic cancer biomarkers, as well as molecular therapeutic
      targets in cancer.

PMID- 17558420
TI  - Imatinib mesylate inhibits cell invasion of malignant peripheral nerve sheath
      tumor induced by platelet-derived growth factor-BB.
AB  - Malignant peripheral nerve sheath tumor (MPNST) is rare, highly aggressive,
      resistant to radiochemotherapy, and associated with poor prognosis. Basic
      research to develop new treatment regimes is critically needed. This study was
      designed to identify motogenic factor(s) involved in MPNST cell invasion and
      inhibitor(s) of such invasive activity. We profiled the invasion-inducing
      activities of eight motogenic growth factors on two human MPNST cell lines, FU
      SFT8611 and 9817, using in vitro Matrigel invasion assays. Platelet-derived
      growth factor-BB (PDGF-BB) was identified as the most effective MPNST cell
      invasion-inducing factor. Epidermal growth factor (EGF) and hepatocyte growth
      factor (HGF) also stimulated invasion in one MPNST cell line. Expressions of PDGF
      BB and EGF receptors (PDGFR-beta and EGFR) mRNAs were detected more frequently
      and their proteins were expressed at higher levels in MPNST tissues than benign
      peripheral nerve sheath tumors (schwannomas and neurofibromas). In both MPNST
      cell lines, PDGF-BB induced tyrosine phosphorylation of PDGFR-beta but not of
      PDGFR-alpha, and specific PDGFR-beta inhibition by small interfering RNA to the
      receptor inhibited PDGF-BB-stimulated MPNST cell invasion, suggesting the
      predominant role of PDGFR-beta. Inhibition of PDGFR-beta phosphorylation by
      pretreatment with herbimycin A and imatinib mesylate effectively suppressed
      basement membrane invasion and cell growth in vitro. No mutations were present in
      exons 12 and 18 of PDGFR-beta in both MPNST cell lines and 10 human MPNST tissues
      examined. Our results indicated that PDGF-BB enhanced the invasive activity of
      MPNST cells through PDGFR phosphorylation and that imatinib inhibited such
      activity. The results provide the ground for further assessment of the
      therapeutic potential of imatinib in suppressing the invasion and growth of
      MPNST.

PMID- 17558421
TI  - Microarray analyses and molecular profiling of steatosis induction in
      immortalized human hepatocytes.
AB  - Hepatic steatosis is an important risk factor for the development of
      inflammation, fibrosis and impaired liver regeneration. The factors regulating
      lipid accumulation and driving hepatic steatosis toward inflammation, fibrosis
      and impaired regeneration are largely unknown. The aim of this study was to
      identify major alterations in gene expression occurring in steatotic hepatocytes,
      and to analyze how these changes impact cellular processes associated with
      steatosis. Microarray gene chips and RT-PCR were performed to analyze changes in
      gene expression induced in fatty human immortalized hepatocytes after treatment
      with 50 muM oleic acid for 7 days. Lipid metabolism and triglyceride accumulation
      in these cells was examined by Oil-Red-O staining, thin-layer chromatography
      (TLC) and immunofluorescence. Caspase 3 activity, BrdU incorporation and trypan
      blue exclusion were used to study apoptosis, proliferation and cell viability.
      Finally, quantitative analysis of signalling induced by insulin was performed by
      Western blot. Characterization of steatosis in three hepatocyte-derived cell
      lines indicated that the immortalized human hepatocytes (IHH) line was the most
      appropriate cell line for this study. Gene expression analysis showed significant
      alterations in the transcription of two major classes of genes involved either in
      cholesterol and fatty acid biosynthesis, as well as lipid export, or in apoptosis
      and cell proliferation. Such changes were functionally relevant, since TLC
      indicated that synthesis and accumulation of triglycerides were increased in
      steatotic cells, while synthesis of cholesterol and fatty acids were decreased.
      Lipid accumulation in IHH was associated with an increased apoptosis and an
      inhibition of cell proliferation and viability. No detectable changes in genes
      associated with insulin resistance were observed in steatotic cells, but
      signalling induced by insulin was more efficient in steatotic IHH as compared to
      control cells. We conclude that IHH represent a new valuable model of steatosis,
      not associated with insulin resistance, to study at both the genetic and
      functional level factors involved in the process of lipid accumulation and
      steatosis-associated liver injury.

PMID- 17558422
TI  - Real and artificial immune systems: computing the state of the body.
AB  - Here I present the idea that the immune system uses a computational strategy to
      carry out its many functions in protecting and maintaining the body. Along the
      way, I define the concepts of computation, Turing machines and system states. I
      attempt to show that reframing our view of the immune system in computational
      terms is worth our while.

PMID- 17558423
TI  - Pathogenic epitopes, heterologous immunity and vaccine design.
AB  - Substantial research has been directed towards the development of a new
      generation of vaccines that are based on the inclusion of immunogenic epitopes in
      recombinant vectors. Here we examine the evidence that under certain conditions
      immunogenic epitopes can do more harm than good and might therefore be considered
      pathogenic. We suggest that the specific removal of such pathogenic epitopes from
      vaccines might increase their prophylactic potential, while minimizing the risk
      of side-effects from vaccine use.

PMID- 17558424
TI  - Prospects for a dengue virus vaccine.
AB  - The number of cases of severe dengue disease continues to grow in endemic areas
      of southeast Asia, Central and South America, and other subtropical regions.
      Children bear the greatest burden of disease, and the development of an effective
      vaccine remains a global public health priority. A tetravalent vaccine is
      urgently needed and must be effective against all four dengue virus serotypes, be
      cost-effective and provide long-term protection. In this Review we discuss the
      unique immunological concerns in dengue virus vaccine development and the current
      prospects for the development of an acceptable vaccine, a goal that is likely to
      be reached in the near future.

PMID- 17558425
TI  - The contribution of immunology to the rational design of novel antibacterial
      vaccines.
AB  - In most cases, a successful vaccine must induce an immune response that is better
      than the response invoked by natural infection. Vaccines are still unavailable
      for several bacterial infections and vaccines to prevent such infections will be
      best developed on the basis of our increasing insights into the immune response.
      Knowledge of the signals that determine the best possible acquired immune
      response against a given pathogen - comprising a profound T- and B-cell memory
      response as well as long-lived plasma cells - will provide the scientific
      framework for the rational design of novel antibacterial vaccines.

PMID- 17558426
TI  - The perfect mix: recent progress in adjuvant research.
AB  - Developing efficient and safe adjuvants for use in human vaccines remains both a
      challenge and a necessity. Past approaches have been largely empirical and
      generally used a single type of adjuvant, such as aluminium salts or emulsions.
      However, new vaccine targets often require the induction of well-defined cell
      mediated responses in addition to antibodies, and thus new immunostimulants are
      required. Recent advances in basic immunology have elucidated how early innate
      immune signals can shape subsequent adaptive responses and this, coupled with
      improvements in biochemical techniques, has led to the design and development of
      more specific and focused adjuvants. In this Review, I discuss the research that
      has made it possible for vaccinologists to now be able to choose between a large
      panel of adjuvants, which potentially can act synergistically, and combine them
      in formulations that are specifically adapted to each target and to the relevant
      correlate(s) of protection.

PMID- 17558428
TI  - Warping a single Mn acceptor wavefunction by straining the GaAs host.
AB  - Transition-metal dopants such as Mn determine the ferromagnetism in dilute
      magnetic semiconductors such as Ga(1-x)Mn(x)As. Recently, the acceptor states of
      Mn dopants in GaAs were found to be highly anisotropic owing to the symmetry of
      the host crystal. Here, we show how the shape of such a state can be modified by
      local strain. The Mn acceptors near InAs quantum dots are mapped at room
      temperature by scanning tunnelling microscopy. Dramatic distortions and a
      reduction in the symmetry of the wavefunction of the hole bound to the Mn
      acceptor are observed originating from strain induced by quantum dots.
      Calculations of the acceptor-state wavefunction in the presence of strain, within
      a tight-binding model and within an effective-mass model, agree with the
      experimentally observed shape. The magnetic easy axes of strained lightly doped
      Ga(1-x)Mn(x)As can be explained on the basis of the observed local density of
      states for the single Mn spin.

PMID- 17558427
TI  - Clinical trials of Shigella vaccines: two steps forward and one step back on a
      long, hard road.
AB  - More than 50 years of research has yielded numerous Shigella vaccine candidates
      that have exemplified both the promise of vaccine-induced prevention of
      shigellosis and the impediments to developing a safe and effective vaccine for
      widespread use, a goal that has yet to be attained. This Review discusses the
      most advanced strategies for Shigella vaccine development, the immune responses
      that are elicited following disease or vaccination, the factors that have
      accelerated or impeded Shigella vaccine development and our ideas for the way
      forward.

PMID- 17558429
TI  - Self-healing materials with microvascular networks.
AB  - Self-healing polymers composed of microencapsulated healing agents exhibit
      remarkable mechanical performance and regenerative ability, but are limited to
      autonomic repair of a single damage event in a given location. Self-healing is
      triggered by crack-induced rupture of the embedded capsules; thus, once a
      localized region is depleted of healing agent, further repair is precluded. Re
      mendable polymers can achieve multiple healing cycles, but require external
      intervention in the form of heat treatment and applied pressure. Here, we report
      a self-healing system capable of autonomously repairing repeated damage events.
      Our bio-inspired coating-substrate design delivers healing agent to cracks in a
      polymer coating via a three-dimensional microvascular network embedded in the
      substrate. Crack damage in the epoxy coating is healed repeatedly. This approach
      opens new avenues for continuous delivery of healing agents for self-repair as
      well as other active species for additional functionality.

PMID- 17558430
TI  - Synthetic pores with reactive signal amplifiers as artificial tongues.
AB  - The sensation of taste is mediated by activation or deactivation of transmembrane
      pores. Artificial stimulus-responsive pores are enormously appealing as sensor
      components because changes in their activity are readily detectable in many
      different ways. However, the detection of multiple components in complex matrices
      (such as foods) with one pore sensor has so far remained elusive because the
      specificity necessary for sensing a target compound in complex mixtures is
      incompatible with the broad applicability needed for the detection of multiple
      components. Here, we present synthetic pores that, like our tongues, can sense
      flavours in food and in addition make them visibly detectable. Differential
      sensing and pattern recognition are solutions based on empirical and biomimetic
      approaches. They have been explored with synthetic receptor arrays and electronic
      tongues. In contrast, our approach is non-empirical as it exploits reactive
      amplifiers that covalently capture elusive analytes after enzymatic signal
      generation and drag them into synthetic pores for blockage. Reactive
      amplification proved to be highly sensitive and adaptable to various analytes and
      pores. Moreover, it can be combined with reactive filtration for minimizing
      interference. The system was tested on real food samples for detection of
      sucrose, lactose, lactate, acetate, citrate and glutamate to demonstrate the
      feasibility of these synthetic pores as universal sensors.

PMID- 17558431
TI  - Substrate-induced magnetic ordering and switching of iron porphyrin molecules.
AB  - To realize molecular spintronic devices, it is important to externally control
      the magnetization of a molecular magnet. One class of materials particularly
      promising as building blocks for molecular electronic devices is the paramagnetic
      porphyrin molecule in contact with a metallic substrate. Here, we study the
      structural orientation and the magnetic coupling of in-situ-sublimated Fe
      porphyrin molecules on ferromagnetic Ni and Co films on Cu(100). Our studies
      involve X-ray absorption spectroscopy and X-ray magnetic circular dichroism
      experiments. In a combined experimental and computational study we demonstrate
      that owing to an indirect, superexchange interaction between Fe atoms in the
      molecules and atoms in the substrate (Co or Ni) the paramagnetic molecules can be
      made to order ferromagnetically. The Fe magnetic moment can be rotated along
      directions in plane as well as out of plane by a magnetization reversal of the
      substrate, thereby opening up an avenue for spin-dependent molecular electronics.

PMID- 17558432
TI  - The second extracellular loop of alpha2A-adrenoceptors contributes to the binding
      of yohimbine analogues.
AB  - BACKGROUND AND PURPOSE: Rodent alpha(2A)-adrenoceptors bind the classical
      alpha(2)-antagonists yohimbine and rauwolscine with lower affinity than the human
      alpha(2A)-adrenoceptor. A serine-cysteine difference in the fifth transmembrane
      helix (TM; position 5.43) partially explains this, but all determinants of the
      interspecies binding selectivity are not known. Molecular models of alpha(2A)
      adrenoceptors suggest that the second extracellular loop (XL2) folds above the
      binding cavity and may participate in antagonist binding. EXPERIMENTAL APPROACH:
      Amino acids facing the binding cavity were identified using molecular models:
      side chains of residues 5.43 in TM5 and xl2.49 and xl2.51 in XL2 differ between
      the mouse and human receptors. Reciprocal mutations were made in mouse and human
      alpha(2A)-adrenoceptors at positions 5.43, xl2.49 and xl2.51, and tested with a
      set of thirteen chemically diverse ligands in competition binding assays. KEY
      RESULTS: Reciprocal effects on the binding of yohimbine and rauwolscine in human
      and mouse alpha(2A)-adrenoceptors were observed for mutations at 5.43, xl2.49 and
      xl2.51. The binding profile of RS-79948-197 was reversed only by the XL2
      substitutions. CONCLUSIONS AND IMPLICATIONS: Positions 5.43, xl2.49 and xl2.51
      are major determinants of the species preference for yohimbine and rauwolscine of
      the human versus mouse alpha(2A)-adrenoceptors. Residues at positions xl2.49 and
      xl2.51 determine the binding preference of RS-79948-197 for the human alpha(2A)
      adrenoceptor. Thus, XL2 is involved in determining the species preferences of
      alpha(2A)-adrenoceptors of human and mouse for some antagonists.

PMID- 17558433
TI  - Modulation by simvastatin of iberiotoxin-sensitive, Ca2+-activated K+ channels of
      porcine coronary artery smooth muscle cells.
AB  - BACKGROUND AND PURPOSE: Statins (3-hydroxy-3-methyl-glutaryl coenzyme A (HMG CoA)
      reductase inhibitors) have been demonstrated to reduce cardiovascular mortality.
      It is unclear how the expression level of HMG CoA reductase in cardiovascular
      tissues compares with that in cells derived from the liver. We hypothesized that
      this enzyme exists in different cardiovascular tissues, and simvastatin modulates
      the vascular iberiotoxin-sensitive Ca2+-activated K(+) (BK(Ca)) channels.
      EXPERIMENTAL APPROACHES: Expression of HMG CoA reductase in different
      cardiovascular preparations was measured. Effects of simvastatin on BK(Ca)
      channel gatings of porcine coronary artery smooth muscle cells were evaluated.
      KEY RESULTS: Western immunoblots revealed the biochemical existence of HMG CoA
      reductase in human cardiovascular tissues and porcine coronary artery. In porcine
      coronary artery smooth muscle cells, extracellular simvastatin (1, 3 and 10
      microM) (hydrophobic), but not simvastatin Na+ (hydrophilic), inhibited the
      BK(Ca) channels with a minimal recovery upon washout. Isopimaric acid (10 microM)
      mediated enhancement of the BK(Ca) amplitude was reversed by external
      simvastatin. Simvastatin Na+ (10 microM, applied internally), markedly attenuated
      isopimaric acid (10 microM)-induced enhancement of the BK(Ca) amplitude. Reduced
      glutathione (5 mM; in the pipette solution) abolished simvastatin -elicited
      inhibition. Mevalonolactone (500 microM) and geranylgeranyl pyrophosphate (20
      microM) only prevented simvastatin (1 and 3 microM)-induced responses.
      simvastatin (10 microM ) caused a rottlerin (1 microM)-sensitive (cycloheximide
      (10 microM)-insensitive) increase of PKC-delta protein expression. CONCLUSIONS
      AND IMPLICATIONS: Our results demonstrated the biochemical presence of HMG CoA
      reductase in different cardiovascular tissues, and that simvastatin inhibited the
      BK(Ca) channels of the arterial smooth muscle cells through multiple
      intracellular pathways.

PMID- 17558434
TI  - The effect of the palmitoylethanolamide analogue, palmitoylallylamide (L-29) on
      pain behaviour in rodent models of neuropathy.
AB  - BACKGROUND AND PURPOSE: Cannabinoids are associated with analgesia in acute and
      chronic pain states. A spectrum of central cannabinoid (CB(1)) receptor-mediated
      motor and psychotropic side effects limit their therapeutic potential. Here, we
      investigate the analgesic effect of the palmitoylethanolamide (PEA) analogue,
      palmitoylallylamide (L-29), which via inhibition of fatty acid amide hydrolase
      (FAAH) may potentiate endocannabinoids thereby avoiding psychotropic side
      effects. EXPERIMENTAL APPROACH: The in vivo analysis of the effect of L-29 on
      measures of pain behaviour in three rat models of neuropathic pain. KEY RESULTS:
      Systemically administered L-29 (10 mg kg(-1)) reduced hypersensitivity to
      mechanical and thermal stimuli in the partial sciatic nerve injury (PSNI) model
      of neuropathic pain; and mechanical hypersensitivity in a model of antiretroviral
      (ddC)-associated hypersensitivity and a model of varicella zoster virus (VZV)
      associated hypersensitivity. The effects of L-29 were comparable to those of
      gabapentin (50 mg kg(-1)). The CB(1) receptor antagonist SR141716a (1 mg kg(-1))
      and the CB(2) receptor antagonist SR144528 (1 mg kg(-1)) reduced the effect of L
      29 on hypersensitivity in the PSNI and ddC models, but not in the VZV model. The
      peroxisome proliferator-activated receptor-alpha antagonist, MK-886 (1 mg kg(
      1)), partially attenuated the effect of L-29 on hypersensitivity in the PSNI
      model. L-29 (10 mg kg(-1)) significantly attenuated thigmotactic behaviour in the
      open field arena without effect on locomotor activity. CONCLUSIONS AND
      IMPLICATIONS: L-29 produces analgesia in a range of neuropathic pain models. This
      presents L-29 as a novel analgesic compound that may target the endogenous
      cannabinoid system while avoiding undesirable side effects associated with direct
      cannabinoid receptor activation.

PMID- 17558435
TI  - Virodhamine and CP55,940 modulate cAMP production and IL-8 release in human
      bronchial epithelial cells.
AB  - BACKGROUND AND PURPOSE: We investigated expression of cannabinoid receptors and
      the effects of the endogenous cannabinoid virodhamine and the synthetic agonist
      CP55,940 on cAMP accumulation and interleukin-8 (IL-8) release in human bronchial
      epithelial cells. EXPERIMENTAL APPROACH: Human bronchial epithelial (16HBE14o(-))
      cells were used. Total mRNA was isolated and cannabinoid receptor mRNAs were
      detected by RT-PCR. Expression of CB(1) and CB(2) receptor proteins was detected
      with Western blotting using receptor-specific antibodies. cAMP accumulation was
      measured by competitive radioligand binding assay. IL-8 release was measured by
      ELISA. KEY RESULTS: CB(1) and CB(2) receptor mRNAs and proteins were found. Both
      agonists concentration-dependently decreased forskolin-induced cAMP accumulation.
      This effect was inhibited by the CB(2) receptor antagonist SR144528, and was
      sensitive to Pertussis toxin (PTX), suggesting the involvement of CB(2) receptors
      and G(i/o)-proteins. Cell pretreatment with PTX unmasked a stimulatory component,
      which was blocked by the CB(1) receptor antagonist SR141716A. CB(2) receptor
      mediated inhibition of cAMP production by virodhamine and CP55,940 was paralleled
      by inhibition of tumor necrosis factor-alpha (TNF-alpha) induced IL-8 release.
      This inhibition was insensitive to SR141716A. In the absence of agonist, SR144528
      by itself reduced TNF-alpha induced IL-8 release. CONCLUSIONS AND IMPLICATIONS:
      Our results show for the first time that 16HBE14o(-) cells respond to virodhamine
      and CP55,940. CB(1) and CB(2) receptor subtypes mediated activation and
      inhibition of adenylyl cyclase, respectively. Stimulation of the dominant CB(2)
      receptor signalling pathway diminished cAMP accumulation and TNF-alpha-induced IL
      8 release. These observations may imply that cannabinoids exert anti-inflammatory
      properties in airways by modulating cytokine release.

PMID- 17558436
TI  - The adenosine A1 receptor antagonist SLV320 reduces myocardial fibrosis in rats
      with 5/6 nephrectomy without affecting blood pressure.
AB  - BACKGROUND AND PURPOSE: Myocardial fibrosis is an unwanted effect associated with
      chronic renal failure. The adenosine system is involved in cardiac and renal
      function. Therefore, we investigated the novel selective adenosine A(1) receptor
      antagonist SLV320 focusing on its potential in preventing cardiomyopathy in rats
      with 5/6 nephrectomy. EXPERIMENTAL APPROACH: Male Sprague-Dawley rats were
      allocated to 4 groups of 12 rats each: 5/6 nephrectomy (5/6 NX), 5/6 NX plus
      SLV320 (10 mg kg(-1) d(-1) mixed with food), sham and sham plus SLV320. Study
      duration was 12 weeks, blood pressure was assessed repeatedly. At study end
      kidney function was assessed, blood samples and hearts were taken for
      histology/immunohistochemistry. Pharmacological properties of SLV320 were
      assessed using receptor binding and enzyme assays and in vivo. KEY RESULTS:
      SLV320 is a selective and potent adenosine A(1) antagonist in vitro (Ki=1 nM)
      with a selectivity factor of at least 200 versus other adenosine receptor
      subtypes. Functional A(1) antagonism was demonstrated in vivo. In rats with 5/6
      NX SLV320 significantly decreased albuminuria by about 50%, but did not alter
      glomerular filtration rate (GFR). SLV320 normalized cardiac collagen I+III
      contents in 5/6 NX rats. SLV320 prevented nephrectomy-dependent rise in plasma
      levels of creatinine kinase (CK), ALT and AST. Blood pressure did not differ
      between study groups. CONCLUSION: SLV320 suppresses cardiac fibrosis and
      attenuates albuminuria without affecting blood pressure in rats with 5/6
      nephrectomy, indicating that selective A(1) receptor antagonists may be
      beneficial in uraemic cardiomyopathy.

PMID- 17558437
TI  - Peripheral and central H1 histamine receptor occupancy by levocetirizine, a non
      sedating antihistamine; a time course study in the guinea pig.
AB  - BACKGROUND AND PURPOSE: The H(1) receptor occupancy (H1RO) in brain is an
      indicator of central side effects of antihistamines. Here, we determined the
      kinetics of central and peripheral H1RO by levocetirizine in relation to its
      brain and plasma concentration, and investigated the role of the blood-brain
      barrier in any delay in brain H1RO. EXPERIMENTAL APPROACH: Concentration-time
      profiles in plasma and brain were obtained after 0.1 and 1 mg kg(-1) oral doses
      of levocetirizine in guinea pigs. H1RO in brain was measured ex vivo using [3H]
      mepyramine and, in the periphery, by measuring the degree of inhibition of
      histamine-induced contractions of isolated guinea pig ileum. KEY RESULTS: The
      concentration-time profile of levocetirizine indicated lower levels (partition
      coefficient, K(p)=0.06-0.08), higher t(max) (2-4 h vs 1-1.5 h) and longer
      terminal half-life (4-5.6 h vs 2.1-2.8 h) in brain than plasma. The H1RO at 0.1
      and 1 mg kg(-1) were 75% and 97%, respectively, at 1 hr in the periphery and, in
      the brain, were <20% and 28-67% respectively, at all time points studied. Brain
      H1RO vs plasma concentrations profile showed a delay, but not when compared to
      brain concentrations. CONCLUSIONS AND IMPLICATIONS: This study demonstrates an
      effective peripheral antihistamine effect of levocetirizine without central
      adverse effects at the dose close to human therapeutic dose. The slow increase in
      H1RO in the brain with time was caused by slow blood-brain barrier transport of
      levocetirizine. This demonstrates the importance of measuring time course of
      brain H1RO in relation to brain concentrations of drugs.

PMID- 17558438
TI  - A 17beta-derivative of allopregnanolone is a neurosteroid antagonist at a
      cerebellar subpopulation of GABA A receptors with nanomolar affinity.
AB  - BACKGROUND AND PURPOSE: High-affinity, subtype-selective antagonists of the
      neurosteroid binding sites of GABA(A) receptors are not available. We have
      characterized an allopregnanolone derivative as an antagonist of cerebellar
      GABA(A) receptors with nanomolar affinity. EXPERIMENTAL APPROACH: Receptor
      binding and electrophysiological methods were used for the allosteric modulation
      of cerebellar GABA(A) receptors by an allopregnanolone derivative, (20R)-17beta
      (1-hydroxy-2,3-butadienyl)-5alpha-androstane-3alpha-ol (HBAO). GABA(A) receptors
      of rat cerebellar membranes were labelled with the chloride channel blocker
      [(3)H]ethynylbicycloorthobenzoate (EBOB). The ionophore function of GABA(A)
      receptors was studied by whole-cell patch clamp electrophysiology in cultured rat
      cerebellar granule and cortical cells. KEY RESULTS: Partial displacement of
      cerebellar [(3)H]EBOB binding by nanomolar HBAO was attenuated by 0.1 mM
      furosemide, an antagonist of alpha(6) and beta(2-3) subunit-containing GABA(A)
      receptors. Displacement curves of HBAO were reshaped by 30 nM GABA and shifted to
      the right. However, the micromolar potency of full displacement by
      allopregnanolone was not affected by 0.1 mM furosemide or 30 nM GABA. The
      nanomolar, but not the micromolar phase of displacement of [(3)H]EBOB binding by
      GABA was attenuated by 100 nM HBAO. Submicromolar HBAO did not affect [(3)H]EBOB
      binding to cortical and hippocampal GABA(A) receptors. HBAO up to 1 microM did
      not affect chloride currents elicited by 0.3-10 microM GABA, while it abolished
      potentiation by 1 microM allopregnanolone with nanomolar potency in cerebellar
      but not in cortical cells. Furosemide attenuated cerebellar inhibition by 100 nM
      HBAO. CONCLUSIONS AND IMPLICATIONS: HBAO is a selective antagonist of
      allopregnanolone, a major endogenous positive modulator via neurosteroid sites of
      cerebellar (probably alpha(6)beta(2-3)delta) GABA(A) receptors.

PMID- 17558439
TI  - Cardiovascular gene therapy: current status and therapeutic potential.
AB  - Gene therapy is emerging as a potential treatment option in patients suffering
      from a wide spectrum of cardiovascular diseases including coronary artery
      disease, peripheral vascular disease, vein graft failure and in-stent restenosis.
      Thus far preclinical studies have shown promise for a wide variety of genes, in
      particular the delivery of genes encoding growth factors such as vascular
      endothelial growth factor (VEGF) and fibroblast growth factor (FGF) to treat
      ischaemic vascular disease both peripherally and in coronary artery disease. VEGF
      as well as other genes such as TIMPs have been used to target the development of
      neointimal hyperplasia to successfully prevent vein graft failure and in-stent
      restenosis in animal models. Subsequent phase I trials to examine safety of these
      therapies have been successful with low levels of serious adverse effects, and
      albeit in the absence of a placebo group some suggestion of efficacy. Phase 2
      studies, which have incorporated a placebo group, have not confirmed this early
      promise of efficacy. In the next generation of clinical gene therapy trials for
      cardiovascular disease, many parameters will need to be adjusted in the search
      for an effective therapy, including the identification of a suitable vector,
      appropriate gene or genes and an effective vector delivery system for a specific
      disease target. Here we review the current status of cardiovascular gene therapy
      and the potential for this approach to become a viable treatment option.

PMID- 17558441
TI  - Synthesis of Mono- and Di-Deuterated (2S, 3S)-3-Methylaspartic Acids to
      Facilitate Measurement of Intrinsic Kinetic Isotope Effects in Enzymes.
AB  - Kinetic isotope effects provide a powerful method to investigate the mechanisms
      of enzyme-catalyzed reactions, but often other slow steps in the reaction such as
      substrate binding or product release suppress the isotopically sensitive step.
      For reactions at methyl groups, this limitation may be overcome by measuring the
      isotope effect by an intra-molecular competition experiment. This requires the
      synthesis of substrates containing regio-specifically mono- or dideuterated
      methyl groups. To facilitate mechanistic investigations of the adenosylcobalamin
      dependent enzyme, glutamate mutase we have developed a synthesis of mono- and di
      deuterated (2S, 3S)-3-methylaspartic acids. Key intermediates are the
      correspondingly labeled mesaconic acids and their dimethyl esters that
      potentially provide starting materials for a variety of isotopically labeled
      molecules.

PMID- 17558440
TI  - Stimulation of rat erythrocyte P2X7 receptor induces the release of
      epoxyeicosatrienoic acids.
AB  - BACKGROUND AND PURPOSE: Red blood cells (RBCs) are reservoirs of vasodilatory,
      antiaggregatory, and antiinflammatory lipid mediators-epoxyeicosatrienoic acids
      (EETs). This study addresses the formation and release of erythrocyte-derived
      EETs in response to ATP receptor stimulation that may represent an important
      mechanism regarding circulatory regulation. EXPERIMENTAL APPROACH: Erythrocyte
      EET formation and release were investigated by incubating rat RBCs in
      physiological salt solution with agents that effected ATP release via P2 receptor
      stimulation of phospholipase A2 and epoxygenase-like activities with activation
      of the ATP secretory mechanism. EETs were analyzed by gas and liquid
      chromatography-mass spectrometry. KEY RESULTS: EETs were released from rat RBCs:
      14,15-, 11,12-, 8,9- and 5,6-EETs in a ratio of 1.2:1.0:0.9:0.8. EETs were
      produced by epoxidation of arachidonic acid catalyzed by hemoglobin. Spontaneous
      release of EETs, 0.66+/-0.14 ng per 10(9) RBCs, was dose-dependently increased by
      an ATP analog, BzATP, and inhibited by P2X(7) receptor antagonists. 5 microM ATP
      increased release of EETs over 20% to 0.83+/-0.15 ng per 10(9) RBCs; 10 microM
      BzATP tripled the amount of EET release to 1.87+/-0.20 ng per 10(9) RBCs. EET
      release by ATP or BzATP was not associated with hemolysis. Carbenoxolone, a gap
      junction inhibitor that inhibits ATP release, and glibenclamide, an inhibitor of
      the cystic fibrosis transmembrane conductance regulator (CFTR), which is required
      for ATP release, inhibited the spontaneous and stimulated EET release from RBCs.
      CONCLUSIONS AND IMPLICATIONS: EETs are produced and released from RBCs via a
      mechanism that is mediated by ATP stimulation of P2X(7) receptors coupled to ATP
      transporters, pannexin-1 and CFTR.

PMID- 17558442
TI  - The Friendships of Young Children with Developmental Delays: A Longitudinal
      Analysis.
AB  - This longitudinal study examined the social interactions of children with mild
      developmental (cognitive) delays with friends across the early childhood and
      early elementary years. Results revealed increases in many forms of social
      exchange with effect sizes in the moderate range, but no changes in sustained
      interactive play. Social interaction patterns, difficulties in identifying
      friends to participate in the study, and concerns evident in children's peer and
      friendship networks suggest the general absence of reciprocal friendships. These
      findings are consistent with the hypothesis that children's limited peer-related
      social competence constrains all aspects of their development of friendships.
      Despite these problems, the potential benefits of interventions designed to
      support relationships at this stage of friendship development for children with
      delays were noted.

PMID- 17558443
TI  - Increased connexin 43 expression improves the migratory and proliferative ability
      of H9c2 cells by Wnt-3a overexpression.
AB  - The change of connexin 43 (Cx43) expression and the biological behaviors of Cx43
      in rat heart cell line H9c2, expressing Wnt-3a (wingless-type MMTV integration
      site family, member 3A), were evaluated in the present study. Plasmid
      pcDNA3.1/Wnt-3a was constructed and transferred into H9c2 cells. The cell model
      Wnt-3a(+)-H9c2 steadily expressing Wnt-3a was obtained. Compared with H9c2 and
      pcDNA3.1-H9c2 cells, the expression of Cx43 in Wnt-3a(+)-H9c2 cells was clearly
      increased, the proliferation of Wnt-3a(+)-H9c2 cells was significantly changed,
      and cell migration abilities were also improved(P<0.05). In comparison with H9c2
      and pcDNA3.1-H9c2 cells, the G2 phase of the cell cycle increased by 11% in Wnt
      3a(+)-H9c2 cells. Thus, Wnt-3a overexpression is associated with an increase in
      Cx43 expression and altered migratory and proliferative activity in H9c2 cells.
      Cx43 might be one of the downstream target genes regulated by Wnt-3a.

PMID- 17558444
TI  - Microarray analysis of the developing rat mandible.
AB  - To analyze the molecular events that occur in the developing mandible, we
      examined the expression of 8803 genes from samples taken at different time points
      during rat postnatal mandible development. Total RNA was extracted from the
      mandibles of 1-day-old, 1-week-old, and 2-week-old rats. Complementary RNA (cRNA)
      was synthesized from cDNA and biotinylated. Fragmented cRNA was hybridized to RG
      U34A GeneChip arrays. Among the 8803 genes tested, 4344 were detectable. We
      identified 148 genes with significantly increased expression, and 19 genes with
      significantly decreased expression. A comprehensive analysis appears to be an
      effective method of studying the complex process of development.

PMID- 17558445
TI  - Spectroscopic analysis on the effect of temperature on Kunitz domain 1 of human
      tissue factor pathway inhibitor-2.
AB  - The conformation of Kunitz domain 1 of human tissue factor pathway inhibitor-2
      (hTFPI-2/KD1) has been studied by fourier transform infrared spectroscopy,
      circular dichroism, and Raman spectroscopy. It was found that hTFPI-2/KD1
      contained approximately 17% alpha-helices, 24% beta-strands, 46% random coils,
      13% beta-turns, and two kinds of disulfide bonds(ggg and tgt) at 25 degrees C.
      The detailed conformational changes of the heated protein observed by fourier
      transform infrared spectroscopy, circular dichroism and Raman spectroscopy
      revealed that hTFPI-2/KD1 was thermally stable. However, KD1 could form an
      intermediate form at high temperature, then return to its normal conformation
      when the temperature was lowered. Activity assays also showed that hTFPI-2/KD1
      was able to keep its inhibitory activity on plasmin after being heated to 80
      degrees C for 5 min.

PMID- 17558446
TI  - Pharmacophore-directed homology modeling and molecular dynamics simulation of G
      protein-coupled receptor: study of possible binding modes of 5-HT2C receptor
      agonists.
AB  - A new pharmacophore-based modeling procedure, including homology modeling,
      pharmacophore study, flexible molecular docking, and long-time molecular dynamics
      (MD) simulations, was employed to construct the structure of the human 5-HT(2C)
      receptor and determine the characteristics of binding modes of 5-HT(2C) receptor
      agonists. An agonist-receptor complex has been constructed based on homology
      modeling and a pharmacophore hypothesis model based on some high active
      compounds. Then MD simulations of the ligand-receptor complex in an explicit
      membrane environment were carried out. The conformation of the 5-HT(2C) receptor
      during MD simulation was explored, and the stable binding modes of the studied
      agonist were determined. Flexible molecular docking of several structurally
      diverse agonists of the human 5-HT(2C) receptor was carried out, and the general
      binding modes of these agonists were investigated. According to the models
      presented in this work and the results of Flexi-Dock, the involvement of the
      amino acid residues Asp134, Ser138, Asn210, Asn331, Tyr358, Ile131, Ser132,
      Val135,Thr139, Ile189, Val202, Val208, Leu209, Phe214, Val215, Gly218, Ser219,
      Phe223, Trp324, Phe327, and Phe328 in agonist recognition was studied. The
      obtained binding modes of the human 5-HT(2C) receptor agonists have good
      agreement with the site-directed mutagenesis data and other studies.

PMID- 17558447
TI  - Adenovirus-mediated expression of both antisense ornithine decarboxylase and S
      adenosylmethionine decarboxylase inhibits lung cancer cell growth.
AB  - Polyamine biosynthesis is controlled primarily by ornithine decarboxylase (ODC)
      and S-adenosylmethionine decarboxylase (AdoMetDC). Antisense sequences of ODC and
      AdoMetDC genes were cloned into an adenoviral vector (named Ad-ODC-AdoMetDCas).
      To evaluate the effects of recombinant adenovirus Ad-ODC-AdoMetDCas that can
      simultaneously express both antisense ODC and AdoMetDC, the human lung cancer
      cell line A-549 was infected with Ad-ODC-AdoMetDCas or the control vector. Viable
      cell counting, determination of polyamine concentrations, cell cycle analysis,
      and Matrigel invasion assays were carried out to assess the properties of tumor
      growth and invasiveness. Our study showed that adenovirus-mediated antisense ODC
      and AdoMetDC expression inhibits tumor cell growth through blocking the polyamine
      synthesis pathway. Tumor cells were arrested at the G1 phase after gene transfer
      and the invasiveness was reduced. It suggested that the recombinant adenovirus Ad
      ODC-AdoMetDCas might be a new anticancer reagent in the treatment of lung
      cancers.

PMID- 17558448
TI  - Synergy between cucumber mosaic virus and zucchini yellow mosaic virus on
      Cucurbitaceae hosts tested by real-time reverse transcription-polymerase chain
      reaction.
AB  - Cucumber mosaic virus (CMV) and zucchini yellow mosaic virus (ZYMV) are two
      principal viruses infecting cucurbitaceous crops, and their synergy has been
      repeatedly observed. In our present work, a real-time reverse transcription
      polymerase chain reaction procedure was established to study the accumulation
      kinetics of these two viruses in single and combined infections at the molecular
      level. The accumulations of open reading frames (ORFs) for 1a, 2a, 3a and coat
      protein (CP) of CMV and CP of ZYMV were tested. In the single infection, CMV-Fny
      ORFs accumulated to their maxima in cucumber or bottle gourd at 14 d post
      inoculation (dpi), and gradually declined thereafter. ZYMV-SD CP ORF reached
      maximal accumulation at 14 and 28 dpi on cucumber and bottle gourd, respectively.
      However, when co-infected with CMV-Fny and ZYMV-SD, the maximal accumulation
      levels of all viral ORFs were delayed. CMV-Fny ORFs reached their maxima at 21
      dpi on both hosts, and ZYMV-SDCP ORF reached maximal accumulation at 21 and 28
      dpi on cucumber and bottle gourd, respectively. Generally, the accumulation
      levels of CMV-Fny ORFs in the co-infection were higher than those in the single
      infection, whereas the accumulation of ZYMV-SD CP ORF showed a reverse result.

PMID- 17558449
TI  - Two potent alpha3/5 conotoxins from piscivorous Conus achatinus.
AB  - Every cone snail produces a mixture of different conotoxins and secretes them to
      immobilize their prey and predators. alpha3/5 Conotoxins, isolated from fish
      hunting cone snails, target muscle nicotinic acetylcholine receptors. The
      structure and function of alpha3/5 conotoxin from the piscivorous Conus achatinus
      have not been studied. We synthesized two pentadecamer peptides, Ac1.1a and
      Ac1.1b, with appropriate disulfide bonding, based on cDNA sequences of alpha3/5
      conotoxins from C. achatinus. Ac1.1a and Ac1.1b differ by only one amino acid
      residue. They have similar potency on blocking recombinant mouse muscle
      acetylcholine receptor expressed in Xenopus laevis oocytes, with IC50 values of
      36 nM and 26 nM, respectively. For Ac1.1b, deletion of the first three N-terminal
      amino acids did not change its activity, indicating that the N-terminus is not
      involved in the interaction with its receptor. Furthermore, our experiments
      indicate that both toxins strongly prefer the alpha1-delta subunit interface
      instead of the alpha1-gamma binding site on the mouse muscle nicotinic
      acetylcholine receptor. These peptides provide additional tools for the study of
      the structure and function of nicotinic receptor.

PMID- 17558450
TI  - A lectin from Chinese mistletoe increases gammadelta T cell-mediated cytotoxicity
      through induction of caspase-dependent apoptosis.
AB  - In this study, a mistletoe lectin (ML) was purified from Chinese mistletoe and
      the effect of this 60 kDa Chinese ML on human gammadelta T cell cytotoxicity,
      apoptosis and modulation of the cytokine network was studied. The cytotoxic
      properties of delta T cells was evaluated by using a (51)Cr release test and
      employed fluorescence-activated cell sorting and enzyme-linked immunosorbent
      assay analysis to quantify translocation of the cell membrane phospholipid,
      phosphatidylserine and nuclear DNA fragmentation during apoptosis. It was found
      that: (i) ML effectively stimulated gammadelta T cell proliferation in a dose-
      and time-dependent manner; (ii) ML increased gammadelta T cell cytotoxicity;
      (iii) ML could modulate lipopolysaccharide-induced cytokine release in a pro
      inflammatory manner by increasing tumor necrosis factor (TNF)-alpha release and
      inhibiting the release of anti-inflammatory interleukin (IL)-10; (iv) ML induced
      apoptosis in caspase-dependent and CD95-independent manner. The results indicated
      that ML is a potent immunomodulator to human gammadelta T cell cytotoxicity,
      apoptos is and cytokine production.

PMID- 17558451
TI  - hELP3 subunit of the Elongator complex regulates the transcription of HSP70 gene
      in human cells.
AB  - The human Elongator complex is remarkably similar to its yeast counterpart in
      several aspects. In a previous study, we analyzed the functions of the human
      elongation protein 3 (hELP3) subunit of the human Elongator by using an in vivo
      yeast complementation system. However, direct evidence for hELP3 functions in
      regulating gene expression in human cells was not obtained. In this study, we
      used hELP3 antisense oligonucleotide inhibitors to knock down hELP3 gene
      expression to investigate its function in human 293T cells. The results showed
      that specific reduction of hELP3 mRNA and protein caused a significant
      suppression of HSP70-2 gene expression, and this was accompanied by histone H3
      hypoacetylation and decreased RNA polymerase II density at the HSP70-2 gene.
      Moreover, the data also showed that hELP3 exerted the transcriptional regulatory
      function directly through its presence on the HSP70-2 gene. Data presented in
      this report provide further insight and direct evidence of the functions of hELP3
      in HSP70-2 gene transcriptional elongation in human cells.

PMID- 17558452
TI  - Molecular cloning, expression and characterization of ribokinase of Leishmania
      major.
AB  - Ribokinase (EC 2.1.7.15) from Leishmania major was cloned, sequenced and
      overexpressed in Escherichia coli. The gene expressed an active enzyme that had
      comparable activity to the same enzyme studied in E. coli. It specifically
      phosphorylated D-ribose. Under defined conditions, the K(m) for the substrates D
      ribose and ATP were 0.3+/-0.04 mM and 0.2+/-0.02 mM, respectively. The turnover
      numbers of the enzyme for the substrates were 10.8 s(-1) and 10.2 s(-1),
      respectively. The enzyme product ribose 5-phosphate inhibited the phosphorylation
      of D-ribose with an apparent K(i) of 0.4 mM, which is close to the K(m) (0.3 mM)
      of D-ribose, suggesting that it might play a role in regulating flux through the
      enzyme.

PMID- 17558453
TI  - Field assessment of sediment toxicities within a subtropical estuarine wetland in
      Hong Kong, using a local gastropod (Sermyla tornatella).

PMID- 17558454
TI  - Bilateral traumatic carotid-cavernous fistulae: Strategies for endovascular
      treatment.
AB  - BACKGROUND: Most traumatic carotid-cavernous fistula/e (TCCF) are unilateral, and
      simultaneous bilateral TCCF are uncommon. The purpose of this study was to
      evaluate the angiographic architecture of bilateral TCCF and report our
      experience with their endovascular management. METHOD: Over 15 years, 252
      consecutive patients with TCCF were referred to our institute for endovascular
      treatment. Bilateral TCCF occurred in 5 men and 2 women with a mean age of 31
      years. The angiographic architectures of bilateral TCCF were evaluated with
      cerebral angiography. All patients underwent a single session of transarterial
      embolisation by using various permanent embolic materials and were followed up
      clinically or with angiography for a mean of 22 months (range 9-36 months).
      FINDINGS: All patients presented with neuro-ophthalmic symptoms and signs. No new
      instances of cerebrovascular ischemia or intracranial haematoma resulted from
      bilateral TCCF. All fistulae were associated with partial arterial steal and were
      successfully occluded by using a detachable balloon and/or a detachable coil with
      or without a liquid adhesive. Of 14 TCCF, 9 were completely obliterated with
      preserved flow of the internal carotid artery (ICA). In the other 5 fistulae, the
      ICA had to be sacrificed to achieve occlusion because the anatomy of the fistula
      was complex. All fistula related symptoms resolved immediately or gradually
      during clinical follow up. No clinically significant procedure related
      neurological complications or recurrent fistulae were observed. CONCLUSIONS: All
      bilateral TCCF were associated with a partial arterial steal phenomenon. Single
      session endovascular treatment using various embolic materials was effective in
      managing these high-flow fistulae. In all patients, it was possible to preserve
      one or both ICAs.

PMID- 17558455
TI  - Huge primary myxoma of skull base: a report of an uncommon case.
AB  - We report a 27-year-old male who presented with paroxysmal headache, stuffy nose,
      epistaxis and impairment of vision in each eye. A huge chondrosarcoma, arising
      from the skull base with extension into the middle cranial fossa and nasal cavity
      was suspected. The patient underwent craniotomy and endoscope-assisted transnasal
      resection and a satisfactory removal was achieved. Postoperative
      immunohistochemical examination confirmed the diagnosis of myxoma rather than
      chondrosarcoma. The patient remained neurologically intact except for poor vision
      in the left eye at six-month follow-up. The relevant literature was reviewed and
      discussed. The main treatment of myxomas of cranial base is by surgery.

PMID- 17558456
TI  - Transclival cerebrospinal fluid fistula in a patient with Marfan's syndrome.
AB  - Marfan's syndrome is a disease associated with reduced structural integrity of
      connective tissues. We report a 36-year-old patient with Marfan's syndrome who
      presented with rhinorrhoea, occipital headache and vomiting. Physical examination
      revealed typical Marfan's syndrome features including dolicocephalous, mandibular
      micrognathia, tall stature, disproportionately long limbs and digits, and
      hypermobility of the joints. A high-resolution CT scan demonstrated
      pneumoencephalous, cerebrospinal fluid (CSF) filling the sphenoidal sinus, and a
      small bone defect of the clivus. Surgery performed through a transsphenoidal
      approach revealed the sphenoid sinus to be filled with CSF and a small
      fenestration in the clivus. The arachnoid diverticulum and the fenestration were
      repaired and covered with a graft of abdominal fat. In this patient, a deficiency
      in bone development associated with Marfan's syndrome gave rise to a clival
      fenestration and a transclival CSF fistula. Although abnormalities of the spinal
      meningeal membranes have been reported in Marfan's syndrome, to our knowledge,
      this is the first report of a fistula located in the cranial base in this
      condition.

PMID- 17558457
TI  - Osteopathia striata with cranial sclerosis and lumbar spinal stenosis.
AB  - Osteopathia striata with cranial sclerosis is one of the dysplasias of
      endochondral bone formation. We report a patient with this condition combined
      with lumbar spinal stenosis and intervertebral disc herniation. This coexistence
      has not been previously reported in the medical literature. The possible
      mechanisms of this clinical association is discussed.

PMID- 17558458
TI  - Peduncular hallucinosis after sacrifice of veins of the petrosal venous complex
      for trigeminal neuralgia.
AB  - Peduncular hallucinosis is characterized by striking visual images, highly
      colored and mobile, which are recognized by the patient as imaginary. A 50-year
      old-man underwent microvascular decompression for a classical right sided
      trigeminal neuralgia. During the procedure, the petrosal vein and a transverse
      pontine vein were sacrificed for trigeminal decompression. On the second
      postoperative day, the patient developed peduncular hallucinosis that disappeared
      on the forth postoperative day. This is the third case in the literature of
      peduncular hallucinosis after obliteration of veins of the petrosal venous
      complex for trigeminal neuralgia. The best policy in cerebellopontine angle
      surgery is to preserve the petrosal vein whenever possible to avoid complications
      related to venous congestion.

PMID- 17558459
TI  - Supratentorial dural-based hemangioblastoma not associated with von Hippel Lindau
      complex.
AB  - Hemangioblastomas are rarely found in a supratentorial location and are commonly
      associated with the von Hippel-Lindau complex. Therefore, patients with such
      tumors must be evaluated for both other hemangioblastomas within the central
      nervous system as well as for this complex via physical examination, radiographic
      examination, and genetic testing. We report the seventh case of a patient with an
      isolated supratentorial dural based hemangioblastoma not associated with the von
      Hippel-Lindau complex.

PMID- 17558460
TI  - Treatment of vestibular schwannomas. Why, when and how?
AB  - Sporadic vestibular schwannoma (VS) causes unilateral hearing loss, tinnitus,
      vertigo and unsteadiness. In many cases, the tumour size may remain unchanged for
      many years following diagnosis, which is typically made by MRI. In the majority
      of cases the tumour is small, leaving the clinician and patient with the options
      of either serial scanning or active treatment by gamma knife radiosurgery (GKR)
      or microneurosurgery. Despite the vast number of published treatment reports,
      comparative studies are few, and evidence is no better than class III (May,
      2006). The predominant clinical endpoints of VS treatment include tumour control,
      facial nerve function and hearing preservation. Less focus has been put on
      symptom relief and health-related quality of life (QOL). It is uncertain if
      treating a small tumour leaves the patient with a better chance of obtaining
      relief from future hearing loss, vertigo or tinnitus than by observing it without
      treatment. Recent data indicate that QOL is reduced in untreated VS patients, and
      may differ between patients who have been operated and patients treated with GKR.
      In the present paper we review the natural course and complaints of untreated VS
      patients, and the treatment alternatives and results. Furthermore, we review the
      literature concerning quality of life in patients with VS. Finally, we present
      our experience with a management strategy applied to more than 300 cases since
      2001.

PMID- 17558461
TI  - Botulinum toxin in the treatment of blepharospasm and hemifacial spasm.
AB  - Blepharospasm and hemifacial spasm are the two most common craniofacial movement
      disorders. Blepharospasm is a syndrome characterized by excessive or continuous
      eye closure related to overactivity of the orbicularis oculi and adjacent muscles
      bilaterally. Hemifacial spasm is a peripherally-induced movement disorder
      typically caused by vascular compression of cranial nerve VII (CN VII) leading to
      involuntary unilateral contractions of muscles used in facial expression.
      Treatment options for both conditions include medications, botulinum toxin, and
      various surgical interventions. This article summarizes the existing medical
      literature which indicates that botulinum toxin is the treatment of choice for
      blepharospasm and hemifacial spasm.

PMID- 17558462
TI  - The association of Y chromosome haplogroups with spermatogenic failure in the Han
      Chinese.
AB  - A significant proportion of male infertility is accompanied by an abnormal semen
      analysis, azoospermia or severe oligozoospermia, which is generally assumed to be
      the result of spermatogenic failure. The genetic contribution in the process of
      spermatogenesis, particularly the role of the Y chromosome in determination of
      semen quality, is still obscure. In order to explore the relationship between Y
      chromosome haplogroup and spermatogenic failure, we collected 285 idiopathic
      infertile males with azoo-/oligozoospermia and 515 fertile men, adopted 12 binary
      markers and recruited the subjects (cases and controls) in the same region to
      test whether there is a possible susceptibility of certain Y haplogroups to
      spermatogenic failure in the Han Chinese population. The results indicated that
      the prevalences of hg K in the control and the case population were 0.78% (4/515)
      and 2.80% (8/285), respectively. The difference between the frequencies of the hg
      K in the infertile males and the normal control population was significant [odds
      ratio (OR) = 3.69; 95% confidence interval (CI) = 1.10-12.36] (P = 0.028).
      However, in the other haplogroups no significant differences were found. In
      conclusion, Y haplogroup-K might bear a risk factor of male infertility, and the
      individuals in the haplogroup need to be further examined.

PMID- 17558463
TI  - Thyroid disease in Sjogren's syndrome.
AB  - From 1960 to 2007, an important number of patients with primary Sjogren's
      syndrome (pSS) along with thyroid disease diagnosed by laboratory data and
      clinical presentation were reported. The most common thyroid disorder found was
      autoimmune thyroiditis and the most common hormonal pattern was subclinical
      hypothyroidism. The coexistence of SS and thyroiditis is frequent and suggests a
      common genetic or environmental factor predisposition with similar pathogenic
      mechanisms. pSS was ten times more frequent in patients with autoimmune thyroid
      disease and autoimmune thyroiditis was nine times more frequent in pSS.
      Therefore, SS should be studied in patients with thyroid disease and vice versa.
      Antigens are shared by both thyroid and salivary glands, which could be
      responsible for the association between both diseases. Immunogenetic studies had
      suggested that both diseases have a common genetic predisposition. pSS and
      thyroid disease patients were mostly women with positive antithyroglobulin,
      antiparietal cell and antithyroid peroxidase antibodies. Thyroid dysfunction is
      frequent in pSS patients and those prone to develop thyroid disorders are
      identified by thyroid-related autoantibodies or by rheumatoid factor and anti
      Ro/SSA activity. Patients with pSS have an increased tendency to develop other
      autoimmune diseases. Hypothyroidism was the most common autoimmune disease
      developed in pSS patients during follow-up of 10.5 years. Lymphomas are also
      associated with SS and thyroiditis and a 67-fold increased risk for thyroid
      mucosa-associated lymphoid tissue (MALT) lymphoma and a 44-fold increased risk
      for parotid lymphoma is being attributed to autoimmune thyroiditis and pSS. It is
      suggested that immune mechanism deficiency is a causal factor for B cell lymphoma
      in pSS and autoimmune thyroid disease. Other studies are necessary to clarify the
      shared pathogenesis mechanism in SS and autoimmune thyroid disease and to
      understand this fascinating autoimmune association.

PMID- 17558464
TI  - The international classification for functioning, disability and health. A
      challenge and a need for rheumatology.

PMID- 17558465
TI  - Diffusive wave spectroscopy of a random close packing of spheres.
AB  - We are interested in the propagation of light in a random packing of dielectric
      spheres within the geometrical optics approximation. Numerical simulations are
      performed using a ray tracing algorithm. The effective refractive indexes and the
      transport mean free path are computed for different refractive indexes of spheres
      and intersticial media. The variations of the optical path length under small
      deformations of the spheres assembly are also computed and compared to the
      results of Diffusive Wave Spectroscopy experiments. Finally, we propose a measure
      of the transport mean free path and a Diffusive Wave Spectroscopy experiment on a
      packing of glass spheres. The results of those experiments agree with the
      predictions of this ray tracing approach.

PMID- 17558466
TI  - The metabolism and function of sphingolipids and glycosphingolipids.
AB  - Sphingolipids and glycosphingolipids are emerging as major players in many facets
      of cell physiology and pathophysiology. We now present an overview of
      sphingolipid biochemistry and physiology, followed by a brief presentation of
      recent advances in translational research related to sphingolipids. In discussing
      sphingolipid biochemistry, we focus on the structure of sphingolipids, and their
      biosynthetic pathways--the recent identification of most of the enzymes in this
      pathway has led to significant advances and better characterization of a number
      of the biosynthetic steps, and the relationship between them. We then discuss
      some roles of sphingolipids in cell physiology, particularly those of ceramide
      and sphingosine-1-phosphate, and mention current views about how these lipids act
      in signal transduction pathways. We end with a discussion of sphingolipids and
      glycosphingolipids in the etiology and pathology of a number of diseases, such as
      cancer, immunity, cystic fibrosis, emphysema, diabetes, and sepsis, areas in
      which sphingolipids are beginning to take a central position, even though many of
      the details remain to be elucidated.

PMID- 17558467
TI  - Mechanisms of sperm-egg interactions emerging from gene-manipulated animals.
AB  - Untangling the molecular nature of sperm-egg interactions is fundamental if we
      are to understand fertilization. These phenomena have been studied for many years
      using biochemical approaches such as antibodies and ligands that interact with
      sperm or with eggs and their vestments. However, when homologous genetic
      recombination techniques were applied, most of the phenotypic factors of the gene
      manipulated animals believed "essential" for fertilization were found to be
      dispensable. Of course, all biological systems contain redundancies and
      compensatory mechanisms, but as a whole the old model of fertilization clearly
      requires significant modification. In this review, we use the results of gene
      manipulation experiments in animals to propose the basis for a new vision.

PMID- 17558468
TI  - Modulation of protein biophysical properties by chemical glycosylation:
      biochemical insights and biomedical implications.
AB  - Glycosylation constitutes one of the most important posttranslational
      modifications employed by biological systems to modulate protein biophysical
      properties. Due to the direct biochemical and biomedical implications of
      achieving control over protein stability and function by chemical means, there
      has been great interest in recent years towards the development of chemical
      strategies for protein glycosylation. Since current knowledge about glycoprotein
      biophysics has been mainly derived from the study of naturally glycosylated
      proteins, chemical glycosylation provides novel insights into its mechanistic
      understanding by affording control over glycosylation parameters. This review
      presents a survey of the effects that natural and chemical glycosylation have on
      the fundamental biophysical properties of proteins (structure, dynamics,
      stability, and function). This is complemented by a mechanistic discussion of how
      glycans achieve such effects and discussion of the implications of employing
      chemical glycosylation as a tool to exert control over protein biophysical
      properties within biochemical and biomedical applications.

PMID- 17558469
TI  - Angiotensin-converting enzyme 2 in acute respiratory distress syndrome.
AB  - Angiotensin-converting enzyme (ACE) and ACE2 are highly homologous
      metalloproteases that provide essential catalytic functions in the renin
      angiotensin system (RAS). Angiotensin II is one key effector peptide of the RAS,
      inducing vasoconstriction and exerting multiple biological functions. ACE cleaves
      angiotensin I to generate angiotensin II, whereas ACE2 reduces angiotensin II
      levels. Accumulating evidence has demonstrated a physiological and pathological
      role of ACE2 in the cardiovascular systems. Intriguingly, the SARS coronavirus,
      the cause of severe acute respiratory syndrome (SARS), utilizes ACE2 as an
      essential receptor for cell fusion and in vivo infections. Moreover, recent
      studies have demonstrated that ACE2 protects murine lungs from acute lung injury
      as well as SARS-Spike protein-mediated lung injury, suggesting a dual role of
      ACE2 in SARS infections and protection from ARDS.

PMID- 17558470
TI  - Predicting 13Calpha chemical shifts for validation of protein structures.
AB  - The (13)C(alpha) chemical shifts for 16,299 residues from 213 conformations of
      four proteins (experimentally determined by X-ray crystallography and Nuclear
      Magnetic Resonance methods) were computed by using a combination of approaches
      that includes, but is not limited to, the use of density functional theory.
      Initially, a validation test of this methodology was carried out by a detailed
      examination of the correlation between computed and observed (13)C(alpha)
      chemical shifts of 10,564 (of the 16,299) residues from 139 conformations of the
      human protein ubiquitin. The results of this validation test on ubiquitin show
      agreement with conclusions derived from computation of the chemical shifts at the
      ab initio Hartree-Fock level. Further, application of this methodology to 5,735
      residues from 74 conformations of the three remaining proteins that differ in
      their number of amino acid residues, sequence and three-dimensional structure,
      together with a new scoring function, namely the conformationally averaged root
      mean-square-deviation, enables us to: (a) offer a criterion for an accurate
      assessment of the quality of NMR-derived protein conformations; (b) examine
      whether X-ray or NMR-solved structures are better representations of the observed
      (13)C(alpha) chemical shifts in solution; (c) provide evidence indicating that
      the proposed methodology is more accurate than automated predictors for
      validation of protein structures; (d) shed light as to whether the agreement
      between computed and observed (13)C(alpha) chemical shifts is influenced by the
      identity of an amino acid residue or its location in the sequence; and (e)
      provide evidence confirming the presence of dynamics for proteins in solution,
      and hence showing that an ensemble of conformations is a better representation of
      the structure in solution than any single conformation.

PMID- 17558471
TI  - Sublethal effects of spirodiclofen on life history and life-table parameters of
      two-spotted spider mite (Tetranychus urticae).
AB  - Laboratory bioassays were conducted to evaluate the effects of spirodiclofen on
      life history and life-table parameters of two-spotted spider mite (Tetranychus
      urticae Koch) females treated at pre-ovipositional period with a series of
      acaricide concentrations starting with the concentration discriminative for eggs
      and immatures i.e. the lowest concentration that causes 100% mortality of those
      stages. After a 24 h exposure, the proportion of females that survived treatments
      was 0.71 (6 mg/l), 0.51 (12 mg/l), 0.41 (24 mg/l), 0.30 (48 mg/l) and 0.25 (96
      mg/l). At the end of the trial, the survival rate of females treated with the
      lowest concentration was significantly lower than the survival rate of untreated
      females but it remained above that of females treated with higher concentrations.
      Total fecundity/fertility significantly decreased as concentrations of
      spirodiclofen increased. Viable eggs were laid by females treated with 6, 12 and
      24 mg/l, and total fertility was reduced by 42, 84 and 97%, respectively.
      Compared with control, the gross fecundity/fertility of the treated females was
      significantly reduced throughout the trial, except in females treated with 6
      mg/l. All concentrations caused a significant reduction in the net
      fecundity/fertility throughout the trial. The females treated with 12 mg/l had
      significantly reduced net reproductive rate (R0 = 6.45), compared to females
      treated with 6 mg/l (R0 = 23.35) and to untreated females (R0 = 28.92); there was
      no significant difference between the last two treatments. The intrinsic rate of
      increase (r(m)) and finite rate of increase (lambda) were significantly reduced
      in treated females (r(m)) = 0.141, lambda = 1.156 and r(m) = 0.214, lambda =
      1.232; 12 and 6 mg/l, respectively), compared to control (r(m) = 0.251, lambda =
      1.276). The reduction was significantly greater in females treated with the
      highest concentration. As a result of the lowered r(m), the doubling time in
      treated females was significantly extended. Sublethal effects of spirodiclofen
      and its impact on T. urticae management are discussed.

PMID- 17558472
TI  - Evaluation of bone response to titanium-coated polymethyl methacrylate resin
      (PMMA) implants by X-ray tomography.
AB  - High-resolution three-dimensional data about the bone response to oral implants
      can be obtained by using microfocus computer tomography. However, a disadvantage
      is that metallic implants cause streaking artifacts due to scattering of X-rays,
      which prevents an accurate evaluation of the interfacial bone-to-implant contact.
      It has been suggested that the use of thin titanium coatings deposited on
      polymeric implants can offer an alternative option for analyzing bone contact
      using micro-CT imaging. Consequently, the aim of the current study was to
      investigate bone behavior to titanium-coated polymethylmethacrylate (PMMA)
      implants by micro-CT and histological evaluation. For the experiment titanium
      coated PMMA implants were used. The implants had a machined threaded appearance
      and were provided with a 400-500 nm thick titanium coating. The implants were
      inserted in the right or left tibia of 10 goats. After an implantation period of
      12 weeks the implants were retrieved and prepared for micro-computer tomography
      (microCT), light microscopy, and X-ray microanalysis. The micro-CT showed that
      the screw-threads and typical implant configuration were well maintained through
      the installation procedure. Overall, histological responses showed that the
      titanium-coated implants were well tolerated and caused no atypical tissue
      response. In addition, the bone was seen in direct contact with the titanium
      coated layer. The X-ray microanalysis results confirmed the light microscopical
      data. In conclusion, the obtained results proof the final use of titanium-coated
      PMMA implants for evaluation of the bone-implant response using microCT. However,
      this study also confirms that for a proper analysis of the bone-implant interface
      the additional use of microscopical techniques is still required.

PMID- 17558473
TI  - Load bearing capacity of bone anchored fiber-reinforced composite device.
AB  - The purpose of this study was to evaluate the push-out load-bearing capacity of
      threaded fiber-reinforced composite (FRC) devices for use as bone-anchored
      devices. The purpose was also to evaluate the possibility to use bioactive glass
      (BAG) granules on the experimental FRC devices in terms the mechanical behavior.
      Three experimental FRC devices (n = 15) were fabricated for the study: (a)
      threaded device with smooth surface; (b) threaded device with BAG granules
      (S53P4, Vivoxid Ltd, Turku, Finland) and supplementary retention grooves, and (c)
      unthreaded device with BAG granules. Threaded titanium devices were used as
      controls. The FRC devices were prepared from a light-polymerized dimethacrylate
      resin reinforced with preimpregnated unidirectional and bidirectional E-glass
      fibers (EverStick, StickTech Ltd, Turku, Finland). Experimental and control
      devices were embedded into dental plaster to simulate bone before the mechanical
      push-out test was carried out. ANOVA and Weibull analysis were used for the
      statistical evaluation. Threaded FRC devices had significantly higher push-out
      strength than the threaded titanium device (p < .001). The push-out forces
      exceeding 2,500 N were measured for threaded FRC devices with supplementary
      grooves and BAG coating. No thread failures were observed in any FRC devices. The
      unthreaded FRC devices with BAG lost 70% of glass particles during the test,
      while no BAG particles were lost from threaded FRC devices. It can be concluded
      that threaded FRC devices can withstand high push-out forces in the dental
      plaster without a risk of thread failure under physiological load.

PMID- 17558474
TI  - Cross-linkage of hydroxyapatite/gelatin nanocomposite using imide-based zero
      length cross-linker.
AB  - Hydroxyapatite [HAp]/Gelatin [GEL] nanocomposite was prepared at 37 and 48
      degrees C through coprecipitation process. The HAp/GEL nanocomposite slurries
      were cross-linked by imide-based zero-length cross-linking agent such as N-(3
      dimethylaminopropyl)-N'-ethylcarbodiimide (EDC) and N-hydroxysuccinimide (NHS).
      The chemical bond formation and microstructure in HAp/GEL nanocomposite was
      investigated as a function of cross-linking agents and temperature. The single
      addition of EDC into the composite slurries resulted in a tougher microstructure
      in both samples prepared at 37 and 48 degrees C. However, in the case of the
      simultaneous addition of EDC and NHS the sample prepared at 48 degrees C showed a
      coarse microstructure. These results were consistent with the fact that the
      chemical reactivity of NHS is degraded at 48 degrees C whereas the reactivity of
      EDC increases up to 80 degrees C.

PMID- 17558476
TI  - Stealth dendrimers for antiarrhythmic quinidine delivery.
AB  - Dendrimers have been attracting growing attention because of their unique well
      defined globular nanoscale architecture and numerous functional groups on the
      surface. Attachment of PEG to the dendrimer generates stealth dendrimers, which
      have promising structural advantages for drug delivery. In this study, synthetic
      methods were explored to deliver antiarrhythmic quinidine by stealth dendrimers.
      In particular, quinidine was covalently attached to anionic G2.5 and cationic
      G3.0 polyamidoamine (PAMAM) dendrimers via a glycine spacer, respectively. The
      resulting quinidine-PAMAM-PEG conjugates were characterized and confirmed by FT
      IR and (1)H-NMR. In vitro hydrolysis was carried out in pH 7.4 PBS buffer at 37
      degrees C to confirm the bioavailability of the conjugated quinidine.

PMID- 17558475
TI  - Histological study of surface modified three dimensional poly (D, L-lactic acid)
      scaffolds with chitosan in vivo.
AB  - Biocompatibility and tissue regenerating capacity are essential for biomaterials
      that used in tissue engineering. The aim of this study was to histologically
      assess the tissue reactions and bone conductivities of surface modified three
      dimensional (3-D) poly (D, L-lactic acid) (PDLLA) scaffolds, which were coated
      with chitosan via a physical entrapment method. The native PDLLA scaffold was
      prepared via thermally induced phrase separation technique and was characterized
      by scanning electron microscopy (SEM) and differential scanning calorimetry
      (DSC). Osteocalcin assay, a method to evaluate the bone formation potential, has
      shown that the osteocalcin production in chitosan-modified 3-D PDLLA scaffold
      group was significantly higher (p < 0.05) than that of in control. The tissue
      reactions and bone conductivities between surface modified PDLLA and native PDLLA
      scaffolds were evaluated using a rabbit radialis defect model in vivo and
      compared at different implantation intervals (2, 4, 8 and 12 weeks). The
      histological results have shown a higher bone formation potential and better
      biocompatibility of chitosan-modified 3-D PDLLA scaffolds as compared with the
      control group scaffolds.

PMID- 17558477
TI  - In vitro release of cisplatin from sol-gel processed organically modified silica
      xerogels.
AB  - SiO2, SiO2/PEG and SiO2/PDMS xerogels were examined as polymeric carriers for the
      controlled release of cisplatin--an antineoplasmic medicine. Drug/carrier systems
      were prepared by the sol-gel method. The effect of organic substitution of the
      silica xerogel matrix and drying conditions on the release of cisplatin was
      evaluated. Based on the presented results of the study it may be stated that sol
      gel method is useful for entrapping a cisplatin in the pores of organically
      modified silica gels and for releasing cisplatin mainly in the way of diffusion
      from the pores of the lattice under the in vitro conditions. The use of organic
      impurities in silica gel increased the release of cisplatin from xerogel (from
      62% to 97% within 7 days), and thermal treatment of all xerogels with cisplatin
      at the temperature of 80 degrees C resulted in the acceleration of the drug
      release (2 days) and increase of the released drug (89-98%).

PMID- 17558478
TI  - Effect of cavity preparation method on microtensile bond strength of a self
      etching primer vs phosphoric acid etchant to enamel.
AB  - This study evaluated the effect of cavity preparation using air abrasion or
      carbide bur on bond strength to enamel treated with a self-etching primer (Tyrian
      SPE) or a phosphoric acid etchant. Twenty-four molars were divided into three
      groups: high-speed; standard handpiece (ST air abrasion) or supersonic handpiece
      (SP air abrasion) of the same air-abrasive system. The enamel surfaces were
      treated with one of the two etchants and the same adhesive agent One Step Plus,
      and then composite buildups were done with Filtek Z250. After 24 h at 37 degrees
      C, beams (0.8 mm2) were obtained and subjected to tensile stress in a universal
      testing machine (0.5 mm/min). The data were submitted to analysis of variance and
      Tukey's test (P < 0.05). For the conditioning agents, it was observed that the
      specimens conditioned with phosphoric acid presented superior results than the
      specimens that used Tyrian SPE. For the preparation techniques, it was verified
      that the SP air abrasion groups showed the highest bond strengths and carbide-bur
      groups presented the lowest bond strengths when the specimens were conditioned
      with Tyrian SPE. It can be concluded that the influence of the cavity preparation
      method was dependent on the conditioning system used, only when using carbide-bur
      preparation technique.

PMID- 17558480
TI  - Surface characterization of colloidal-sol gel derived biphasic HA/FA coatings.
AB  - Hydroxyapatite (HA) powders are ultrasonically dispersed in the precursor of
      fluoridated hydroxyapatite (FHA) or fluorapatite (FA) to form a "colloidal sol".
      HA/FA biphasic coatings are prepared on Ti6Al4V substrate via dip coating, 150
      degrees C drying and 600 degrees C firing. The coatings show homogenous
      distribution of HA particles in the FA matrix. The relative phase proportion can
      be tailored by the amount of HA in the colloidal sol. The surfaces of the
      coatings consist of two kinds of distinct domains: HA and FA, resulting in a
      compositionally heterogeneous surface. The biphasic coating surface becomes
      increasingly rougher with HA powders, from around 200 nm of pure FA to 400-600 nm
      in Ra of biphasic coatings. The rougher biphasic HA/FA surfaces with chemically
      controllable domains will favor cell attachment, apatite layer deposition and
      necessary dissolution in clinical applications.

PMID- 17558479
TI  - Microvasculatory reaction of skeletal muscle to Ti-15Mo in comparison to well
      established titanium alloys.
AB  - Beta-titanium alloys such as Ti-15Mo are increasingly utilized for orthopaedic
      implant applications because of their excellent corrosion resistance and low
      elastic modulus. Particularly in osteosynthesis, where the biomaterial stands in
      direct contact to soft tissue, undesirable biologic reactions may have severe
      consequences especially in the vulnerable state of trauma and added iatrogenic
      damage to the microvascular system. In a comparative study we therefore assessed
      in vivo nutritive perfusion and leukocytic response of striated muscle to the
      biomaterials Ti-15Mo, Ti-6Al-4V and Ti-6Al-7Nb, thereby drawing conclusions on
      their short term inflammatory potential. Utilizing the well established skinfold
      chamber preparation in the hamster and intravital fluorescence microscopy, we
      could not demonstrate any significant discrepancies between the three alloys. All
      metals induced an initial moderate inflammatory response in skeletal muscle
      microcirculation. While recuperation of animals treated with Ti-15Mo and Ti-6Al
      7Nb was prompt, we documented a slightly more sluggish recovery of Ti-6Al-4V
      treated animals. A gross toxicity was not observed for any of the alloys.
      Conclusively, Ti-15Mo, Ti-6Al-4V and Ti-6Al-7Nb induce an only transient
      inflammatory answer of the striated muscle microvascular system. Our results
      indicate that on the microvascular level the tested bulk Ti-alloys do not cause
      enduring biologic impairment in muscle.

PMID- 17558481
TI  - Synthesis and characterization of MeO-PEG-PLGA-PEG-OMe copolymers as drug
      carriers and their degradation behavior in vitro.
AB  - The objective of this study was to characterize the methylpoly (ethylene glycol)
      poly (lacticacid-co-glycolicacid)-poly (ethylene-glycol) (MeO-PEG-PLGA-PEG-OMe,
      abbreviation as PELGE) copolymers as intravenous injection drug delivery carriers
      and their degradation behavior in vitro. A series of MeO-PEG-PLGA-PEG-OMe
      copolymers with various molar ratios of lactic to glycolic acid and various
      molecular weights and different MeO-PEG contents were synthesized by ring-opening
      polymerization in the presence of MeO-PEG with molar masses of 2000 and 5000,
      using stannous octoate as the catalyst. The hydrophilicity of PELGE copolymers,
      evaluated by contact angle measurements, was found to increase with an increase
      in their MeO-PEG contents. Methylpoly (ethylene glycol)-poly (lacticacid-co
      glycolicacid) (MeO-PEG-PLGA, abbreviation as PELGA) nanoparticles and PELGE
      nanoparticles were prepared using the emulsion-solvent evaporation technique
      (o/w) with Pluronic F68 (Poloxamer 188 NF) as emulsifier in the external aqueous
      phase. The degradation behavior of the nanoparticles was evaluated by the lactate
      generation with time upon their in vitro incubation in PBS (pH 7.4). The rate of
      in vitro degradation of the PELGE or PELGA nanoparticles depended on their
      composition, increasing with an increase in the proportion of MeO-PEG or LA in
      the copolymer chains. The degradation rate was slower at higher lactide:
      glycolide ratio. The lower the molecular weight of PELGE; the higher the
      degradation rate of the nanoparticles.

PMID- 17558482
TI  - Validation of an abbreviated version of the structured interview of reported
      symptoms in outpatient psychiatric and community settings.
AB  - This study examined the effectiveness of an abbreviated version of the Structured
      Interview of Reported Symptoms (SIRS-A) in identifying malingered mental illness.
      The SIRS-A is comprised of 69 items drawn from the SIRS (R. Rogers et al. 1992,
      SIRS: Structured Interview of Reported Symptoms: Professional Manual. Odessa, FL:
      Psychological Assessment Resources, Inc.), substantially reducing the
      administration time. A simulation design was used with three samples; 87
      psychiatric outpatients who responded honestly were compared to 29 community
      dwelling adults and 24 psychiatric patients instructed to malinger
      psychopathology. The SIRS-A generated sensitivity comparable to or exceeding that
      of the SIRS normative data, but specificity was poorer; many genuinely impaired
      patients were misclassified as malingering. Although these findings suggest the
      SIRS-A may be an effective means to assess malingering in psychiatric
      populations, further research assessing the reasons for the elevated false
      positive rates is necessary.

PMID- 17558483
TI  - Chromatography of living cells using supermacroporous hydrogels, cryogels.
AB  - The preparative cell separation is an intrinsic requirement of various
      diagnostic, biotechnological and biomedical applications. Affinity chromatography
      is a promising technique for cell separation and is based on the interaction
      between a cell surface receptor and an immobilised ligand. Most of the currently
      available matrices have pore size smaller than the size of the cells and are not
      suitable for cell chromatography due to column clogging. Another problem
      encountered in chromatographic separation of cells is a difficulty to elute bound
      cells from affinity surfaces. Application of novel adsorbents, supermacroporous
      monolithic cryogels, allows overcoming these problems. Cryogels are characterised
      by highly interconnected large (10-100 microm) pores, sponge-like morphology and
      high elasticity. They are easily derivatised with any ligand of choice.
      Convective migration can be used to transport the cells through the matrix.
      Target cells bind to affinity ligands, while other cells pass through the cryogel
      column non-retained and are removed during a washing step. Because of the spongy
      and elastic nature of the cryogel matrices, the cells are efficiently desorbed by
      mechanical compression of cryogels, which provides high cell viability and
      yields. The release of affinity bound cells by mechanical compression of a
      cryogel monolithic adsorbent is a unique and efficient way of cell detachment.
      This detachment strategy and the continuous macroporous structure make cryogels
      very attractive for application in cell separation chromatography.

PMID- 17558484
TI  - Proinsulin:insulin and insulin:glucose ratios as predictors of carotid plaque
      growth: a population-based 7 year follow-up of the Tromso Study.
AB  - AIMS/HYPOTHESIS: Proinsulin is increased in persons at cardiovascular risk.
      Increased secretion of proinsulin relative to insulin has been suggested as a
      sign of defective conversion of proinsulin to insulin and C-peptide and is
      associated with beta cell dysfunction. It has also been suggested that proinsulin
      has more of a pro-atherogenic effect than insulin, the levels of which are also
      increased in the insulin resistance state. In this prospective population-based
      study, we examined whether the proinsulin:insulin ratio (PIR) or insulin:glucose
      ratio (IGR, an insulin resistance surrogate) predicted carotid plaque size in
      nondiabetic participants. MATERIALS AND METHODS: The study included 1,859 men and
      1,998 women aged 25-82 years from the Tromso Study, who were examined with B-mode
      high resolution ultrasound at baseline in 1994-1995 and at follow-up in 2001
      2002. All images were computer processed to yield mm(2) measures of plaque.
      Proinsulin and insulin were measured at baseline. All analyses were stratified
      for sex. RESULTS: After adjusting for age, baseline plaque area, BMI,
      cholesterol, HDL-cholesterol, HbA(1c), IGR, albumin:creatinine ratio, fibrinogen,
      BP and lifestyle factors (tobacco smoking, alcohol consumption, physical
      activity), PIR was significantly associated with plaque size at follow-up in
      women but not men. For each SD in the PIR in women, the mean plaque area
      increased by 0.97 mm(2) (95% CI 0.44-1.50). IGR was not associated with carotid
      plaque size. CONCLUSIONS/INTERPRETATION: The PIR is associated with progressive
      carotid artery plaque size in women.

PMID- 17558485
TI  - Chemical gastric inhibitory polypeptide receptor antagonism protects against
      obesity, insulin resistance, glucose intolerance and associated disturbances in
      mice fed high-fat and cafeteria diets.
AB  - AIMS/HYPOTHESIS: Gastric inhibitory polypeptide (GIP) receptor antagonism with
      (Pro(3))GIP improves glucose tolerance and ameliorates insulin resistance and
      abnormalities of islet structure/function in ob/ob mice. This study examined the
      ability of (Pro(3))GIP to counter the development of obesity, insulin resistance
      and diabetes in mice fed high-fat and cafeteria diets. MATERIALS AND METHODS:
      Young Swiss TO mice on standard chow or high-fat, cafeteria or high-carbohydrate
      diets received daily injections of either saline or (Pro(3))GIP (25 nmol kg(
      1)day(-1)) over 16 weeks. Food intake, body weight, and circulating glucose and
      insulin were measured frequently. At 16 weeks, glucose tolerance, insulin
      sensitivity, HbA(1c), circulating hormones and plasma lipids were assessed.
      Adipose tissue, liver and muscle were excised and weighed, and their histology
      and triacylglycerol content were further examined. RESULTS: (Pro(3))GIP
      significantly reduced body weight, enhanced locomotor activity, and improved
      HbA(1c), glucose tolerance, beta cell responsiveness and insulin sensitivity in
      mice fed high-fat and cafeteria diets (p < 0.05 to p < 0.01). Similarly,
      (Pro(3))GIP significantly reduced plasma corticosterone and triacylglycerols (p <
      0.05 to p < 0.001), while glucagon, resistin and adiponectin were unchanged.
      (Pro(3))GIP decreased adipose tissue mass (p < 0.01) and the triacylglycerol
      content of liver, muscle and adipose tissue (p < 0.01 to p < 0.001). Adipocyte
      size and liver morphology were partially normalised. (Pro(3))GIP did not
      significantly affect any of these parameters in mice fed a high-carbohydrate
      diet. CONCLUSIONS/INTERPRETATION: (Pro(3))GIP protects against obesity, insulin
      resistance, glucose intolerance and associated disturbances in mice fed high-fat
      and cafeteria diets. This highlights chemical GIP receptor antagonism as a new
      possibility for the treatment of obesity and associated metabolic disturbances.

PMID- 17558486
TI  - The c-Jun N-terminal kinase JNK participates in cytokine- and isolation stress
      induced rat pancreatic islet apoptosis.
AB  - AIMS/HYPOTHESIS: The protocols used for the preparation of human pancreatic
      islets immediately induce a sustained and massive activation of the c-Jun-N
      terminal kinase (JNK). JNK, which participates in apoptosis of insulin-secreting
      cells, is activated by mechanical stresses, as well as by exposure to pro
      inflammatory cytokines. Here, we investigated whether the delivery of a protease
      resistant JNK inhibitory peptide (D-JNKI) through a protein transduction system
      during pancreatic digestion might impair JNK signalling throughout the
      transplantation procedure. METHODS: Rat pancreases were treated with D-JNKI
      through the pancreatic duct and cells then isolated by enzymatic digestion.
      Protein extracts were prepared to determine JNK activity by kinase assays and
      total RNA was extracted to measure gene expressions by a Light-Cycler technique.
      Cell apoptosis rate was determined by terminal deoxynucleotidyl transferase dUTP
      nick end labelling (TUNEL) assay and by scoring cells displaying pycnotic nuclei.
      RESULTS: Our data establish that the peptide transduction system used here
      efficiently transfects islets, allowing for stable in vivo (up to 2 days)
      transfection of human islets transplanted under the kidney capsule. Further, D
      JNKI decreases intracellular JNK signalling during isolation and following
      cytokine exposure in both human and rat islets, as measured by kinase assays and
      reduced c-fos expression; D-JNKI also confers protection against apoptosis
      induced during the rat islet preparation and subsequent to IL-1beta exposure.
      CONCLUSIONS/INTERPRETATION: JNK signalling participates in islet isolation- and
      IL-1beta-induced apoptosis in rat islets. Furthermore, the system we used might
      be more generally applicable for the persistent blockage (several days) of pro
      apoptotic pathways in the transplanted islets; this days-long protection might
      potentially be an absolute prerequisite to help transplanted islets better
      survive the first wave of the non-specific inflammatory attack.

PMID- 17558487
TI  - Synergy testing of multidrug resistant Acinetobacter baumanii against tigecycline
      and polymyxin using an E-test methodology.

PMID- 17558488
TI  - Comparison of an automated Borrelia indirect chemiluminescent immunoassay (CLIA)
      with a VlsE/C6 ELISA and Immunoblot.

PMID- 17558489
TI  - Pulmonary complications of babesiosis: case report and literature review.
AB  - Reported here is a rare case of babesiosis with pulmonary complications followed
      by a review of the literature. Babesiosis presents clinically as a malaria-like
      illness with fever, chills, headache, fatigue with lymphopenia, atypical
      lymphocytes, mildly or transiently elevated serum transaminases,
      thrombocytopenia, and increased lactate dehydrogenase (LDH) levels. The diagnosis
      of babesiosis is based on identification of Babesia spp. on a peripheral blood
      smear. Babesiosis is usually mild in normal hosts, but it may be severe or even
      fatal in asplenic patients. Pulmonary manifestations are rare in babesiosis, but
      non-cardiogenic pulmonary edema (NCPE) is the most frequent manifestation. NCPE
      in babesiosis does not appear to be related to the degree of parasitemia or
      splenic function and its onset may be early or late. NCPE usually resolves
      rapidly with supportive treatment; it is rarely fatal. Clinicians should suspect
      NCPE in patients with babesiosis who acutely develop shortness of breath and have
      chest radiograph findings compatible with acute pulmonary edema without
      cardiomegaly or pleural effusions.

PMID- 17558490
TI  - The prevalence of post traumatic stress disorder in survivors of ICU treatment: a
      systematic review.
AB  - OBJECTIVE: To determine the prevalence of post traumatic stress disorder in
      survivors of intensive care treatment. DESIGN: Systematic literature review
      including Medline, Embase, CINAHL, PsycINFO and references from identified
      papers. STUDY SELECTION: Studies determining the prevalence of PTSD in adult
      patients who had at least 24[Symbol: see text]h treatment on an intensive care
      unit. Independent duplicate data extraction. Study quality was evaluated in terms
      of study design and method and timing of PTSD assessment. DATA SYNTHESIS AND
      RESULTS: Of the 1472 citations identified, 30 studies meeting the selection
      criteria were reviewed. PTSD was diagnosed by standardised clinical interview
      alone in 2 studies. A self-report measure alone was used in 19 studies to measure
      PTSD symptomatology. The remaining 9 studies applied both standardised clinical
      interview and a self-report measure. The reported prevalence of PTSD was 0-64%
      when diagnosed by standardised clinical interview and 5-64% by self-report
      measure. PTSD assessments occurred 7 days to 8 years after intensive care
      discharge. CONCLUSION: The true prevalence of PTSD and the optimum timing and
      method of PTSD assessment have not yet been determined in intensive care unit
      survivors. Deficiencies in design, methodology and reporting make interpretation
      and comparison of quoted prevalence rates difficult, and rigorous longitudinal
      studies are needed.

PMID- 17558491
TI  - Evidence of altered cortisol metabolism in critically ill patients: a prospective
      study.
AB  - CONTEXT: Changes in cortisol metabolism due to altered activity of the enzyme
      11beta-hydroxysteroid dehydrogenase (11beta-HSD) have been implicated in the
      pathogenesis of hypertension, obesity and the metabolic syndrome. No published
      data exist on the activity of this enzyme in critical illness. OBJECTIVE: To
      investigate cortisol metabolism in critically ill patients utilising plasma
      cortisol: cortisone ratio as an index of 11beta-HSD activity. SETTING: Tertiary
      level intensive care unit. PATIENTS: Three cohorts of critically ill patients:
      sepsis (n = 13); multitrauma (n = 20); and burns (n = 19). MAIN OUTCOME MEASURES:
      Serial plasma cortisol: cortisone ratios. MEASUREMENTS AND MAIN RESULTS: Plasma
      total cortisol cortisone ratios were determined serially after admission to the
      intensive care unit. As compared with controls, the plasma cortisol:cortisone
      ratio was significantly elevated in the sepsis and trauma cohorts on day 1 (22 +/
      9, p = 0.01, and 23 +/- 19, p = 0.0003, respectively) and remained elevated over
      the study period. Such a relationship was not demonstrable in burns. The ratio
      was significantly correlated with APACHE II (r = 0.77, p = 0.0008) and Simplified
      Acute Physiology Score (r = 0.7, p = 0.003) only on day 7 and only in the burns
      cohort. There were no significant correlations observed between total plasma
      cortisol or cortisone and sickness severity in the sepsis and trauma cohorts.
      CONCLUSIONS: In critically ill patients, there is evidence of altered cortisol
      metabolism due to an increase in 11beta-HSD activity as demonstrated by an
      elevation of plasma cortisol: cortisone ratios. Further studies with larger
      sample sizes specifically designed to examine altered tissue 11beta-HSD activity
      and its clinical significance and correlation with outcome are warranted.

PMID- 17558492
TI  - A postural change test improves the prediction of a radiological maxillary
      sinusitis by ultrasonography in mechanically ventilated patients.
AB  - OBJECTIVE: The aim of this study was to evaluate a postural change test during
      sinus ultrasound, compared with CT scan, in case of partial sinusogram to
      differentiate air-fluid level from mucosal thickening. DESIGN: Prospective
      clinical investigation. SETTING: Medical intensive care unit. PATIENTS: 150
      intubated patients. INTERVENTIONS: Patients were examined by sinus ultrasound in
      half-sitting position. A partial sinusogram was defined as the sole visualization
      of the hyperechogenic posterior wall of the sinus. In this situation, a postural
      change was performed and ultrasound was achieved in supine position. If the
      partial sinusogram disappeared when the patient was placed in a supine position
      (positive test), the partial sinusogram was an air-fluid level. If the partial
      sinusogram did not disappear (negative test), we considered it as a mucosal
      thickening. The CT and ultrasound were performed on the same day. Radiological
      maxillary sinusitis (RMS) on CT was defined as the presence of an air-fluid
      level. Absence of RMS on CT was defined as normal sinus or as the presence of
      mucosal thickening. MEASUREMENTS AND RESULTS: 300 sinuses were examined. A
      partial sinusogram was found in 90 sinuses and CT scan confirmed the presence of
      RMS in 55 sinuses (61%). Sensitivity, specificity, positive predictive value, and
      negative predictive value of postural change test compared with CT were,
      respectively, 94.6, 85.6, 91.2 and 90.9%. The positive predictive value increased
      from 61 to 91.2% after the postural change test. CONCLUSIONS: In case of a
      partial sinusogram, a postural change increases the accuracy of ultrasound to
      diagnose RMS.

PMID- 17558493
TI  - Antibiotic management of suspected nosocomial ICU-acquired infection: does
      prolonged empiric therapy improve outcome?
AB  - OBJECTIVE: To characterize empiric antibiotic use in patients with suspected
      nosocomial ICU-acquired infections (NI), and determine the impact of prolonged
      therapy in the absence of infection. DESIGN AND SETTING: Multicenter prospective
      cohort, with eight medical-surgical ICUs in North America and Europe. PATIENTS:
      195 patients with suspected NI. METHODS: The diagnosis of NI was adjudicated by a
      blinded Clinical Evaluation Committee using retrospective review of clinical,
      radiological, and culture data. RESULTS: Empiric antibiotics were prescribed for
      143 of 195 (73.3%) patients with suspected NI; only 39 of 195 (20.0%) were
      adjudicated as being infected. Infection rates were similar in patients who did
      (26 of 143, 18.2%), or did not (13 of 52, 25.0%) receive empiric therapy (p =
      0.3). Empiric antibiotics were continued for more than 4 days in 56 of 95 (59.0%)
      patients without adjudicated NI. Factors associated with continued empiric
      therapy were increased age (p = 0.02), ongoing SIRS (p = 0.03), and hospital (p =
      0.004). Patients without NI who received empiric antibiotics for longer than 4
      days had increased 28-day mortality (18 of 56, 32.1%), compared with those whose
      antibiotics were discontinued (3 of 39, 7.7%; OR = 5.7, 95% CI 1.5-20.9, p =
      0.005). When the influence of age, admission diagnosis, vasopressor use, and
      multiple organ dysfunction was controlled by multivariable analysis, prolonged
      empiric therapy was not independently associated with mortality (OR = 3.8, 95% CI
      0.9-15.5, p = 0.07). CONCLUSIONS: Empiric antibiotics were initiated four times
      more often than NI was confirmed, and frequently continued in the absence of
      infection. We found no evidence that prolonged use of empiric antibiotics
      improved outcome for ICU patients, but rather a suggestion that the practice may
      be harmful.

PMID- 17558495
TI  - Excess ICU mortality attributable to ventilator-associated pneumonia: the role of
      early vs late onset.
AB  - OBJECTIVE: To determine the impact of ventilator-associated pneumonia (VAP) on
      ICU mortality, and whether it is related to time of onset of pneumonia. DESIGN:
      Prospective cohort study. SETTING: 16-bed medical-surgical ICU at a university
      affiliated hospital. PATIENTS AND MEASUREMENTS: From 2002 to 2003, we recorded
      patients receiving mechanical ventilation for > 72 h. Patients developing an
      infection other than VAP were excluded. Patients definitively diagnosed with VAP
      (n=40) were cases and patients free of any infection acquired during ICU stay
      (n=61) were controls. The VAP-attributed mortality was defined as the difference
      between observed mortality and predicted mortality (SAPS II) on admission.
      RESULTS: Mechanical ventilation was longer in VAP patients (25 +/- 20 vs 11 +/- 9
      days; p < 0.001), as was ICU stay (33 +/- 23 vs 14 +/- 12 days; p < 0.001). In
      the non-VAP group, no difference was found between observed and predicted
      mortality (27.9 vs 27.4%; p > 0.2). In the VAP group, observed mortality was 45%
      and predicted mortality 26.5% (p < 0.001), with attributable mortality 18.5%, and
      relative risk (RR) 1.7 (95% CI 1.12-23.17). No difference was observed between
      observed and predicted mortality in early-onset VAP (27.3 vs 25.8%; p > 0.20); in
      late-onset VAP, observed mortality was higher (51.7 vs 26.7%; p < 0.01) with
      attributable mortality of 25% and an RR 1.9 (95% CI 1.26-2.63). Empiric
      antibiotic treatment was appropriate in 77.5% of episodes. No differences in
      mortality were related to treatment appropriateness. CONCLUSIONS: In mechanically
      ventilated patients, VAP is associated with excess mortality, mostly restricted
      to late-onset VAP and despite appropriate antibiotic treatment.

PMID- 17558494
TI  - Genetic variants in the NOD2/CARD15 gene are associated with early mortality in
      sepsis patients.
AB  - OBJECTIVE: Genetic variants in the NOD2/CARD15 gene resulting in a diminished
      capacity to activate NF-kappaB in response to bacterial cell wall products have
      been associated with Crohn's disease (CD). Recently, we found an association
      between the variant Leu1007fsinsC of the NOD2/CARD15 gene (SNP13) and a
      significantly increased rate of transplant related mortality (TRM) due to
      intestinal and pulmonary complications in stem cell transplantation (SCT). To
      assess a possible contribution of variants in the NOD2/CARD15 gene to sepsis
      related mortality (SRM) we investigated 132 prospectively characterised,
      consecutive patients with sepsis. DESIGN AND PATIENTS: The three most common
      NOD2/CARD15 variants (Arg702Trp, Gly908Arg, and Leu1007fsinsC) were determined in
      132 prospectively characterised patients with sepsis attended to three intensive
      care units at the University of Regensburg by Taqman PCR. NOD2/CARD15 genotype
      and major patients' characteristics were correlated with SRM. RESULTS: Patient
      groups with and without NOD2/CARD15 variants did not differ in their clinical
      characteristics such as median age, gender, reason for admission or APACHE score;
      however, SRM (day 30) was increased in patients with NOD2/CARD15 coding variants
      (42 vs. 31%) and was highest (57%) in 8 patients carrying the Leu1007fsinsC
      variant (p < 0.05). Multivariate analysis demonstrated the Leu1007fsinsC genetic
      variant as an independent risk factor for SRM. CONCLUSION: Our findings indicate
      a major role of NOD2/CARD15 coding variants for SRM. This may be indicative for a
      role of impaired barrier function and bacterial translocation in the
      pathophysiology of early sepsis related death.

PMID- 17558496
TI  - Prone equals prone? Impact of positioning techniques on respiratory function in
      anesthetized and paralyzed healthy children.
AB  - OBJECTIVES: Although the prone position is effectively used to improve
      oxygenation, its impact on functional residual capacity is controversial.
      Different techniques of body positioning might be an important confounding
      factor. The aim of this study was to determine the impact of two different prone
      positioning techniques on functional residual capacity and ventilation
      distribution in anesthetized, preschool-aged children. DESIGN: Functional
      residual capacity and lung clearance index, a measure of ventilation homogeneity,
      were calculated using a sulfur-hexafluoride multibreath washout technique. After
      intubation, measurements were taken in the supine position and, in random order,
      in the flat prone position and the augmented prone position (gel pads supporting
      the pelvis and the upper thorax). SETTING: Pediatric anesthesia unit of
      university hospital. PATIENTS AND PARTICIPANTS: Thirty preschool children without
      cardiopulmonary disease undergoing elective surgery. MEASUREMENTS AND RESULTS:
      Mean (range) age was 48.5 (24-80) months, weight 17.2 (10.5-26.9) kg, functional
      residual capacity (mean +/- SD) 22.9+/- 6.2 ml.kg (-1) in the supine position and
      23.3 +/- 5.6 ml.kg (-1) in the flat prone position, while lung clearance indices
      were 8.1 +/- 2.3 vs. 7.9 +/- 2.3, respectively. In contrast, functional residual
      capacity increased to 27.6 +/- 6.5 ml.kg (-1) (p< 0.001) in the augmented prone
      position while at the same time the lung clearance index decreased to 6.7 +/- 0.9
      (p< 0.001). CONCLUSIONS: Functional residual capacity and ventilation
      distribution were similar in the supine and flat prone positions, while these
      parameters improved significantly in the augmented prone position, suggesting
      that the technique of prone positioning has major implications for pulmonary
      function.

PMID- 17558497
TI  - Toxicological comments to the discussion about REACH (H. Greim, M. Arand, H.
      Autrup, H.M. Bolt, J. Bridges, E. Dybing, R. Glomot, V. Foa, R. Schulte-Hermann,
      Arch Toxicol 2006, 80: 121-124). Reply to the letter to the editor: the need for
      a new toxicity testing and risk analysis paradigm to implement REACH or any other
      large scale testing initiative, by B.J. Blaauboer and M.E. Andersen (Arch Toxicol
      2007, 81: 385-387).

PMID- 17558498
TI  - Endogenous thiols enhance thallium toxicity.
AB  - Either L-methionine (L-met) or L-cysteine (L-cys), given alone and in combination
      with Prussian blue (PB) was characterized as treatment against acute thallium
      (Tl) toxicity in rats. Animals were intoxicated with 32 mg/kg Tl acetate
      corresponding to rat LD(50). Antidotal treatments were administered during 4
      days, as follows: (1) vehicle, (2) L-met 100 mg/kg i.p. twice a day, (3) L-cys
      100 mg/kg i.p. twice a day, (4) PB 50 mg/kg oral, twice a day, (5) L-met + PB and
      (6) L-cys + PB. Mortality was as follows: control 50%; L-met 80%; L-cys 80%; PB
      20%; L-met + PB 90% and L-cys + PB 100%. In a different experiment, using 16
      mg/kg of Tl, tissue levels of this metal were analyzed. PB treatment
      statistically diminished Tl content in body organs and brain regions (P<0.01).
      Whereas, separate treatments of L-met and L-cys failed to decrease Tl content in
      organs and brain regions; while its administration in combination with PB (L-met
      + PB and L-cys + PB groups) lowered Tl levels in body organs in the same extent
      as PB group. Results indicate that L-met and L-cys administered alone or in
      combination with PB should not be considered suitable treatments against acute Tl
      toxic effects because this strategy failed to prevent mortality and Tl
      accumulation in brain.

PMID- 17558499
TI  - A conflict rat model of cue-induced relapse to cocaine seeking.
AB  - RATIONALE AND OBJECTIVE: Relapse to drug use in humans can be induced by exposure
      to drug-associated cues. The ability of drug cues to provoke 'relapse' has been
      studied in laboratory animals using a reinstatement model in which resumption of
      drug seeking is assessed after extinction of drug-reinforced responding. In this
      model, there are no adverse consequences of drug-seeking behavior. However, in
      humans, abstinence is often self-imposed, and relapse episodes likely involve
      making a choice between the desire for the drug and the negative consequences of
      pursuing it (a conflict situation). In this paper, we describe a conflict model
      of cue-induced relapse in rats that approximate the human condition. MATERIALS
      AND METHODS: Rats were trained to lever press for cocaine; infusions were paired
      with a discrete light cue. An 'electric barrier' was then introduced by
      electrifying the floor area near the levers. Responding decreased over days with
      increasing shock intensities, until the rats did not approach the levers for 3
      days. Subsequently, the effect of intermittent noncontingent light-cue
      presentations on resumption of lever responding (relapse) was assessed in
      extinction tests, with the electric barrier remaining activated; during testing,
      lever presses led to contingent light-cue presentations. RESULTS: Noncontingent
      cue exposure led to resumption of lever presses during the relapse tests in 14 of
      the 24 rats. Surprisingly, 24 h later, 11 of the 24 rats resumed lever responding
      in a subsequent post-noncontingent cue test under similar extinction conditions.
      Large individual differences in responding were observed during both tests.
      CONCLUSIONS: At its current stage of development, the conflict relapse model
      appears particularly suitable for studying individual differences in cue-induced
      relapse to cocaine seeking or factors that promote this relapse.

PMID- 17558500
TI  - Functional MRI of inhibitory processing in abstinent adolescent marijuana users.
AB  - BACKGROUND: Marijuana intoxication appears to impair response inhibition, but it
      is unclear if impaired inhibition and associated brain abnormalities persist
      after prolonged abstinence among adolescent users. We hypothesized that brain
      activation during a go/no-go task would show persistent abnormalities in
      adolescent marijuana users after 28 days of abstinence. METHODS: Adolescents with
      (n = 16) and without (n = 17) histories of marijuana use were compared on blood
      oxygen level dependent (BOLD) response to a go/no-go task during functional
      magnetic resonance imaging (fMRI) after 28 days of monitored abstinence.
      Participants had no neurological problems or Axis I diagnoses other than cannabis
      abuse/dependence. RESULTS: Marijuana users did not differ from non-users on task
      performance but showed more BOLD response than non-users during inhibition trials
      in right dorsolateral prefrontal, bilateral medial frontal, bilateral inferior
      and superior parietal lobules, and right occipital gyri, as well as during "go"
      trials in right prefrontal, insular, and parietal cortices (p < 0.05, clusters >
      943 microl). Differences remained significant even after controlling for lifetime
      and recent alcohol use. CONCLUSIONS: Adolescent marijuana users relative to non
      users showed increased brain processing effort during an inhibition task in the
      presence of similar task performance, even after 28 days of abstinence. Thus,
      increased brain processing effort to achieve inhibition may predate the onset of
      regular use or result from it. Future investigations will need to determine
      whether increased brain processing effort is associated with risk to use.

PMID- 17558501
TI  - Magnetic resonance cisternography for preoperative evaluation of arachnoid cysts.
AB  - INTRODUCTION: With a high likelihood of clinical improvement and low rates of
      complications, minimally invasive neuroendoscopic surgery is becoming the
      treatment of choice for symptomatic or growing arachnoid cysts. In
      neuroendoscopic surgery, visualization of anatomical landmarks is essential in
      achieving successful fenestration without complications. Because of the
      restricted visual field in neuroendoscopic surgery, preoperative anatomical
      assessment is very helpful. Magnetic resonance cisternography (MRC) with high
      spatial resolution and contrast, using for example 3-D Fourier transformation
      constructive interference in steady state (CISS) or fast imaging employing steady
      state acquisition (FIESTA) sequences, is able to detect the arachnoid cyst wall
      and neighboring anatomical structures as the anatomical landmarks. We
      retrospectively reviewed T2-weighted (T2-W) fast spin-echo images, and the MRC
      and intraoperative findings. METHODS: Axial and coronal T2-W images (6 and 3 mm
      thickness, respectively) and axial and coronal 0.8 mm thick MRC images with CISS
      or FIESTA were obtained from four patients with arachnoid cysts treated by
      neuroendoscopic surgery. Intraoperative findings were reviewed on videotape
      recorded during the procedures. RESULTS: At the brain surface, the arachnoid cyst
      wall could be detected clearly in any of the four patients on MRC images, and was
      only partly seen in the fourth patient T2-W images. Adjacent important anatomical
      structures including vessels and cranial nerves, and an enough space for
      cystocisternostomy were identified on MRC images, and the findings were
      consistent with the findings during neuroendoscopic surgery. CONCLUSION:
      Preoperative identification of the arachnoid cyst wall and surrounding anatomical
      structures by MRC may help avoid complications and allow safer neuroendoscopic
      surgery.

PMID- 17558502
TI  - Transvenous embolization of a dural arteriovenous fistula of the laterocavernous
      sinus through the pterygoid plexus.
AB  - We present a novel access for transvenous embolization of a dural arteriovenous
      fistula of the laterocavernous sinus through the external jugular vein and the
      pterygoid plexus. The anatomy of the laterocavernous sinus is reviewed, and its
      clinical implications discussed in light of the case of a patient whose
      management was modified after identifying this anatomical variation.

PMID- 17558503
TI  - MR imaging characteristics in primary lymphoma of bone with emphasis on non
      aggressive appearance.
AB  - PURPOSE: To assess the heterogeneity of magnetic resonance (MR) imaging
      characteristics in primary lymphoma of bone (PLB), in particular the non
      aggressive appearance. SUBJECTS AND METHODS: In a retrospective study, MR imaging
      features were analyzed in 29 patients with histologically proven PLB. The
      following parameters were evaluated: tumor size, bone marrow and extension into
      soft tissues, signal characteristics of bone marrow and soft-tissue components,
      including enhancement, and involvement of cortical bone (complete disruption,
      focal destruction, permeative destruction and cortical thickening). RESULTS: PLB
      presented with extension into the soft tissue in 22 (76%) of 29 patients, was
      only subtle in three of these 22 patients, and was absent in seven patients.
      Signal intensity (SI) of the soft-tissue part was most frequently homogeneously
      isointense with muscle on T1-weighted images (90%) and high on T2-weighted images
      (91%). Enhancement was predominantly homogeneous and diffuse (82%). In 93% of
      patients cortical bone appeared abnormal: among those patients complete cortical
      disruption was seen in 28%, with extension into soft tissues in all but one
      patient; a permeative pattern of destruction was present in 52% of patients, 66%
      of these had an associated soft-tissue mass. Two patients with normal-appearing
      cortical bone had no extension into soft tissues. In two patients focal cortical
      destruction was noticed; in one patient cortical bone was homogeneously
      thickened, and in one patient PLB was selectively localized within the cortical
      bone. SI of the bone marrow tumor component was more frequently heterogeneous (in
      54%), compared with the soft-tissue component, being high on T2-weighted images
      in 89%, intermediate in 7% and low in 4%. Similarly, enhancement was
      heterogeneous in 59%. CONCLUSION: The MR imaging appearance of PLB is variable.
      In 31% of PLB patients, the tumor was intra-osseous, with linear cortical signal
      abnormalities or even normal-appearing or thickened cortical bone without soft
      tissue mass, and, as such, PLB may not infrequently look non-aggressive on MR
      imaging.

PMID- 17558504
TI  - Mesenchymal stem and progenitor cells for cartilage repair.

PMID- 17558505
TI  - Terminal hemimelia of the lower extremity: absent lateral ray and a normal
      fibula.
AB  - Congenital lateral ray deficiency is considered to be a manifestation of fibular
      hemimelia. However, we have noted patients with absent lateral ray but stable
      knee and ankle joints, and named this condition terminal hemimelia of the lower
      extremity. This study was undertaken to further define this group of patients and
      to compare these patients with fibular hemimelia patients. Four boys and one girl
      of mean age six years two months were in the terminal hemimelic group and four
      boys and three girls of mean age eight years seven months in the fibular
      hemimelic group at the final evaluation. Clinical features commonly observed in
      the fibular hemimelia such as knee valgus, knee instability, tibial bowing, ball
      and socket ankle, ankle instability, tarsal coalition, leg length inequality were
      compared between both groups. Terminal hemimelia of the lower extremity was the
      same as fibular hemimelia in clinical features below the ankle joint. However,
      terminal hemimela was found to be milder than fibular hemimelia in terms of limb
      shortening. The clinical features above the ankle joint were different between
      both groups. Knees and ankles were stable, and gait disturbance were rarely
      noticed in patients with terminal hemimelia of the lower extremity.

PMID- 17558506
TI  - H-type tracheoesophageal fistula with type III laryngotracheoesophageal cleft.
AB  - H-type tracheoesophageal fistula and laryngotracheoesophageal cleft are both rare
      anomalies. Laryngotracheoesophageal clefts are identified as a part of Opitz
      Frias syndrome. We report a neonate with this combination of rare congenital
      anomalies. These associated malformations can have major implications in terms of
      resuscitation, diagnosis and surgical management, which are discussed.

PMID- 17558507
TI  - Tinnitus modifications after cochlear implantation.
AB  - Tinnitus can be defined as a phantom sensation in the absence of an external
      sound. In our study, we evaluated the effect of cochlear implant on tinnitus
      evolution. Among adult, postlingually deaf patients who underwent cochlear
      implantation at our clinic, we selected 20 subjects with pre-implantation
      tinnitus (group A) and 10 subjects without pre-implantation tinnitus (group B).
      Pre- and post-surgery tinnitus was assessed through two questionnaires: the first
      one dealing with tinnitus characteristics and psychosocial impact, and the second
      one represented by THI, an internationally validated score of evaluation of the
      effects of tinnitus on patient's emotions and activities of daily living. None of
      the patients belonging to group B developed tinnitus after surgery. As for group
      A, 40% of patients declared suppression of tinnitus, 30% attenuation of tinnitus
      after surgery, 25% reported tinnitus was unchanged and 5% reported worsening of
      tinnitus. In the nine patients with bilateral tinnitus (45%), after implantation
      tinnitus disappeared from both sides in four patients and attenuated bilaterally
      in four patients. A comparison between pre- and post-implantation THI scores
      showed decreased score in 65% of cases, unchanged score in 30% and increased
      score in 5%. The beneficial effect of cochlear implant on tinnitus, reported by a
      majority of patients, could be due to acoustic masking, to direct electrical
      stimulation of the acoustic nerve, and above all to a possible cochlear
      implantation dependent reorganization of the central auditory pathways and
      associative cerebral areas. In the light of these results, the authors propose
      (1) to include tinnitus in the selection criteria of which ear to implant; (2) to
      consider implantation eligibility for patients with bilateral severe hearing loss
      associated with severe tinnitus; and (3) to inform patients about the small risk
      of post-operative tinnitus worsening.

PMID- 17558508
TI  - Voice improvement in unilateral laryngeal paralysis during loud voicing:
      theoretical impact.
AB  - Voice of patient with unilateral laryngeal paralysis (ULP) shows a nonlinear
      behaviour with sudden octave jumps, bifurcations and chaos. Such a behaviour may
      be due to an increased number of freedom degrees in the glottal system. We
      hypothesized that voice intensity (with increasing sub glottal pressure) could
      improve vocal signal stability with less freedom degrees in vibrating system, and
      then a decrease of nonlinearities. A prospective study of 32 consecutive voices
      of patients with ULP and severe dysphonia was conducted. Jitter and Lyapunov
      exponent from vocal signals were compared at comfortable and loud voicing with
      Wilcoxon's test. In 23 out of 32 patients, jitter significantly decreased from 5
      (median) in normal voice to 1.2 in loud voice (P < 10(-3)), Lyapunov exponent
      decreased from 1,495 bit/s (median) to 708 bit/s (P < 10(-4)). Two patients had
      paradoxical results regarding jitter (higher in loud voice) and 2 regarding
      Lyapunov exponent. From the 23 cases of voice improvement, 15 cases showing a
      marked improvement of the acoustic analysis supported our hypothesis (65%).
      Nonlinear phenomena detected in vocal signals of ULP with severe dysphonia may be
      reduced in loud voice.

PMID- 17558509
TI  - Abstracts of the 6th European Congress of Oto-Rhino-Laryngology Head and Neck
      Surgery, June 30-July 4, 2007, Vienna, Austria.

PMID- 17558514
TI  - Interactions between Mei4, Rec114, and other proteins required for meiotic DNA
      double-strand break formation in Saccharomyces cerevisiae.
AB  - In most sexually reproducing organisms, meiotic recombination is initiated by DNA
      double-strand breaks (DSBs) formed by the Spo11 protein. In budding yeast, nine
      other proteins are also required for DSB formation, but the roles of these
      proteins and the interactions among them are poorly understood. We report further
      studies of the behaviors of these proteins. Consistent with other studies, we
      find that Mei4 and Rec114 bind to chromosomes from leptonema through early
      pachynema. Both proteins showed only limited colocalization with the meiotic
      cohesin subunit Rec8, suggesting that Mei4 and Rec114 associated preferentially
      with chromatin loops. Rec114 localization was independent of other DSB factors,
      but Mei4 localization was strongly dependent on Rec114 and Mer2. Systematic
      deletion analysis identified protein regions important for a previously described
      two-hybrid interaction between Mei4 and Rec114. We also report functional
      characterization of a previously misannotated 5' coding exon of REC102. Sequences
      encoded in this exon are essential for DSB formation and for Rec102 interaction
      with Rec104, Spo11, Rec114, and Mei4. Finally, we also examined genetic
      requirements for a set of previously described two-hybrid interactions that can
      be detected only when the reporter strain is induced to enter meiosis. This
      analysis reveals new functional dependencies for interactions among the DSB
      proteins. Taken together, these studies support the view that Mei4, Rec114, and
      Mer2 make up a functional subgroup that is distinct from other subgroups of the
      DSB proteins: Spo11-Ski8, Rec102-Rec104, and Mre11-Rad50-Xrs2. These studies also
      suggest that an essential function of Rec102 and Rec104 is to connect Mei4 and
      Rec114 to Spo11.

PMID- 17558515
TI  - Kinetics in serum and urinary excretion of ethyl sulfate and ethyl glucuronide
      after medium dose ethanol intake.
AB  - The direct ethanol metabolites, ethyl glucuronide (EtG) and ethyl sulfate (EtS),
      are of increasing importance for clinical and forensic applications, but there
      are only few studies on the kinetics of EtG in serum and none on EtS. In this
      study, 13 volunteers (social drinkers) drank ethanol in the form of white wine to
      reach a blood alcohol concentration of 0.51 +/- 0.17 g/kg, and blood and urine
      samples were analyzed for EtG and EtS simultaneously by chromatography-tandem
      mass spectrometry (LC-MS/MS). Mean peak serum EtG and EtS concentrations were 2.9
      +/- 1.3 and 2.8 +/- 1.6 micromol/l, respectively, and were reached between 4.0 +/
      0.9 h after the start of drinking (3.0 +/- 0.5 h for EtS). The mean time
      differences between reaching maximum blood ethanol levels and serum metabolite
      levels were 2.3 +/- 0.9 h for EtG and 1.2 +/- 0.5 h for EtS. In the last blood
      samples collected (10-11 h after the start of drinking), 11 (of 13) volunteers
      were still positive for EtG in serum, whereas only 2 were positive for EtS. In
      the serum of one female person, no EtS was detectable at any time; however, it
      was excreted in the urine in (low) concentrations. Ethanol was detectable in the
      serum for up to 8.6 h after the start of drinking, whereas EtG and EtS were
      detectable up to more than 5.8 h (EtG) and 4.0 h (EtS), respectively. Mean peak
      urinary concentrations were 401 +/- 232 micromol/l for EtG and 266 +/- 153
      micromol/l for EtS, and mean peak levels were reached 6.2 +/- 0.9 h (EtG) and 5.3
      +/- 1.2 h (EtS) after the start of drinking. Maximum concentrations of EtG and
      EtS in serum showed a wide interindividual variation and could not be correlated
      to the maximum blood ethanol concentrations. Correlations (p < 0.001, Kendall's
      Tau b) were found when comparing pairs of parameters, but mostly involved areas
      under the curve (AUC) of metabolites or of ethanol; one correlation linked the
      peak concentrations of EtG and EtS in urine.

PMID- 17558516
TI  - Energetics of paraplegic cycling: a new theoretical framework and efficiency
      characterisation for untrained subjects.
AB  - Complete lower-limb paralysis resulting from spinal cord injury precludes
      volitional leg exercise, leading to muscle atrophy and physiological de
      conditioning. Cycling can be achieved using phased stimulation of the leg
      muscles. With training there are positive physiological adaptations and health
      improvement. Prior to training, however, power output may not be sufficient to
      overcome losses involved in rotating the legs and little is known about the
      energetics of untrained paralysed muscles. Here we propose efficiency measures
      appropriate to subjects with severe physical impairment performing cycle
      ergometry. These account for useful internal work (i.e. muscular work done in
      moving leg mass) and are applicable even for very low work rates. Experimentally,
      we estimated total work efficiency of ten untrained subjects with paraplegia to
      be 7.6 +/- 2.1% (mean +/- SD). This is close to values previously reported for
      anaesthetised able-bodied individuals performing stimulated cycling exercise, but
      is less than 1/3 of that of able-bodied subjects cycling volitionally.
      Correspondingly, oxygen cost of the work (38.8 +/- 13.9 ml min(-1) W(-1)) was
      found to be approximately 3.5 times higher. This indicates the need, for
      increased power output from paralysed subjects, to maximise muscle strength
      through training, and to improve efficiency by determining better methods of
      stimulating the individual muscles involved in the exercise.

PMID- 17558517
TI  - Alterations in the calcium homeostasis of skeletal muscle from postmyocardial
      infarcted rats.
AB  - In chronic heart failure, skeletal muscles develop a weakness that is not
      associated to an impaired circulatory function but rather to alterations in the
      skeletal muscle fibers themselves. To understand these changes, the steps in
      excitation-contraction coupling of rats that underwent a left anterior coronary
      artery occlusion were studied. About 24 weeks after the myocardial infarction,
      neither the total amount nor the voltage dependence of intramembrane charge were
      altered. In contrast, calcium release from the sarcoplasmic reticulum was
      considerably suppressed, and its voltage dependence shifted toward more positive
      voltages. Elementary calcium-release events showed altered morphology as the
      relative proportion of embers increased. Calcium sparks were smaller in amplitude
      and had larger time-to-peak values. Isolated ryanodine receptors (RyR) displayed
      an unusual rectification with increased single-channel conductance at positive
      (cis vs trans) voltages. In addition, the bell-shaped calcium dependence of
      channel activity was broader, with a slight shift of activation to lower and a
      larger shift in inactivation to higher calcium concentrations. These data
      indicate that the number of channels that open during a calcium-release event is
      decreased and that RyR function is altered; thus, calcium-release is suppressed
      after a myocardial infarction. These observations give an explanation for the
      impaired skeletal muscle function in these animals.

PMID- 17558518
TI  - Temporal changes in myocardial adrenergic regulation with the progression to pump
      dysfunction after chronic beta-adrenoreceptor activation in rats.
AB  - We evaluated the relationship between myocardial norepinephrine release or
      inotropic responsiveness to adrenergic stimulation and intrinsic myocardial
      function after the progression to pump dysfunction induced by chronic beta
      adrenoreceptor activation (isoproterenol [ISO], 0.1 mg/kg/day for 1 month or 6
      months) in rats. Left ventricular (LV) systolic chamber dysfunction occurred
      after 6 months, but not after 1 month of beta-adrenoreceptor activation, as
      evidenced by reduced LV endocardial fractional shortening determined by
      echocardiography and a decrease in the slope of the LV systolic pressure-volume
      relations assessed in isolated, perfused heart preparations. A reduced pump
      function at 6 months of ISO administration was associated with chamber
      dilatation, while LV midwall fractional shortening (echocardiography) and the
      slope of the LV systolic stress-strain relations (isolated heart preparations),
      indices of intrinsic myocardial function, were unchanged. After 1 month of ISO
      administration, reduced beta1- and beta2-adrenoreceptor-mediated and sustained
      alpha-adrenoreceptor-mediated inotropic responses were noted. Nevertheless,
      increased inotropic potency of beta-adrenoreceptor agonists and upregulation of
      alpha-adrenoreceptor-mediated contractile responses were noted after 6 months of
      ISO administration. Increased adrenergic-inotropic responsiveness after 6 months
      of ISO administration was associated with depleted LV norepinephrine stores, as
      evidenced by reduced desipramine-stimulated norepinephrine concentrations in the
      coronary effluent. In conclusion, in the progression from compensated cardiac
      hypertrophy to pump dysfunction after chronic sympathetic activation, a preserved
      intrinsic myocardial contractility is accounted for by paradoxical upregulation
      of adrenergic-mediated contractile responses.

PMID- 17558519
TI  - Nuclear phospholipid signaling: phosphatidylinositol-specific phospholipase C and
      phosphoinositide 3-kinase.
AB  - Over the last 20 years, numerous studies have demonstrated the existence of
      nuclear phosphoinositide signaling distinct from the one at the plasma membrane.
      The activation of phosphatidylinositol-specific phospholipase C (PI-PLC) and
      phosphoinositide 3-kinase (PI3K), the generation of diacylglycerol, and the
      accumulation of the 3-phosphorylated phosphoinositides have been documented in
      the nuclei of different cell types. In this review, we summarize some recent
      studies of the subnuclear localization, mechanisms of activation, and the
      possible physiological roles of the nuclear PI-PLC and PI-3 kinases in the
      regulation of cell cycle, survival, and differentiation.

PMID- 17558520
TI  - Genetic regulation of arrested development in nematodes: are age-1 and daf-gene
      orthologs present in Dictyocaulus viviparus?
AB  - In opposite to the free-living soil nematode Caenorhabditis elegans, the genetic
      regulation of hypobiosis or inhibited or arrested development in parasitic
      nematodes is completely unknown. In C. elegans, the daf-genes or the age-1 gene
      are of major importance in signaling pathways regulating arrested development. To
      investigate if orthologs of these genes are present in the bovine lungworm
      Dictyocaulus viviparus, a PCR analysis with gene-specific primer combinations was
      performed. No orthologs of the age-1 or daf-genes could be identified in D.
      viviparus. The possible differences in the role of the daf-genes concerning
      arrested development in parasitic and free-living nematodes will be discussed.

PMID- 17558521
TI  - Immune response studies with Wuchereria bancrofti vespid allergen homologue
      (WbVAH) in human lymphatic filariasis.
AB  - A homologue of Brugia malayi venom allergen (BmVAH) was cloned from the infective
      stages (L3) of Wuchereria bancrofti. Sequence analysis showed 90% sequence
      identity between WbVAH and BmVAH. Recombinant WbVAH was then expressed and
      purified. VAH from other nematode parasites is being evaluated as potential
      vaccine candidates. Because W. bancrofti infections are more prevalent than B.
      malayi, it will significantly benefit using W. bancrofti antigens for vaccine
      development. In this study, we have evaluated the human immune responses to
      rWbVAH in putatively immune individuals who live in the endemic regions (endemic
      normal, EN) to determine the vaccine potential of WbVAH. These responses were
      then compared to those in infected individuals (microfilaraemic, MF and chronic
      pathology, CP). Results show that EN subjects carry WbVAH-specific IgG1, IgG2,
      and IgG3 circulating antibodies. It is interesting to note that CP patients also
      carried antibodies against WbVAH that was mainly of the IgG3 isotype. Peripheral
      blood mononuclear cells (PBMC) from EN individuals responded strongly to rWbVAH
      by proliferating and secreting IFN-gamma. PBMC from MF patients also proliferated
      in response to rWbVAH but secreted mainly IL-10. Thus, there was a clear
      dichotomy in the cytokine production by infected patients vs individuals who are
      putatively immune (EN). Although vaccine potential of WbVAH has not been
      established yet, our findings suggest that WbVAH mediated immune responses in EN
      individuals is primarily Th1-biased. Further vaccination studies are underway in
      animal models to determine the role of WbVAH in protective immunity against W.
      bancrofti and B. malayi infections.

PMID- 17558522
TI  - Morphological and genetic differences of Trypanosoma in some Chinese freshwater
      fishes: difficulties of species identification.
AB  - Blood smears and purified trypanosome from freshwater fishes yellow catfish
      (Pseudobagras fulvidraco) and common carp (Cyprinus carpio) captured from Niushan
      Lake, Hubei Province were examined to determine whether all of their trypanosomes
      were Trypanosoma pseudobagri, a species of supposed host specificity and
      widespread existence across China. Trypanosomes occurred in 16/16 blood smears,
      and morphometric character analysis of trypanosomes from these smears showed that
      there were three morphospecies, Trypanosoma sp Carpio, T. sp Pseudobagri, and T.
      sp. 18S rDNA sequences of trypanosomes from 16 samples revealed three genetic
      groups among these fish trypanosomes. Group 1 was from C. carpio containing T. sp
      Carpio; groups 2 and 3 were from P. fulvidraco containing T. sp Pseudobagri and
      T. sp, respectively. The high similarity of morphometric characters and 18S rDNA
      sequences showed that T. sp Carpio and T. siniperca probably were the same
      species. T. sp Pseudobagri was the first occurrence in China. Sequence comparison
      showed that T. sp Pseudobagri sequence was most similar to that of clone Marv,
      whereas T. sp sequence differ from those of T. sp Carpio and T. sp Pseudobagri by
      5.4 and 5.8%, respectively, and tentatively identified as T. pseudobagri. It was
      concluded that three species of trypanosomes, at least three genotypes occur in
      Niushan Lake fishes, and P. fulvidraco in this region appear to contain both
      types, although the identification of T. pseudobagri remains a problem.

PMID- 17558523
TI  - Comprehensive investigation of the non-covalent binding of MRI contrast agents
      with human serum albumin.
AB  - Three techniques, electrospray mass spectrometry, ultrafiltration, and proton
      relaxometry, are compared in the context of the quantitative analysis of non
      covalent binding between human serum albumin (HSA) and MRI contrast agents. The
      study of the affinity by proton relaxometry reveals the association constant and
      the number of interaction sites assuming that all sites are identical and
      independent. Ultrafiltration was adapted for the study of paramagnetic complexes.
      This technique confirmed the results obtained by relaxometry. Electrospray mass
      spectrometry, an original method able to study non-covalent binding because of
      its soft ionization process that allows for the survival of weak binding,
      provides qualitative and quantitative results. Electrospray mass spectrometry
      confirmed the affinity measured by proton relaxometry and ultrafiltration. This
      technique requires very small amounts of products and directly gives the
      stoichiometry of the association, information not easily obtained by classic
      techniques. Nevertheless, proton relaxometry remains a useful and mandatory
      technique for determining the enhancement of the relaxation subsequent to the
      binding although it demands large amounts of compounds. It is to be pointed out
      that even if the three techniques lead to a similar ranking of the affinity of
      the contrast agents for HSA, the absolute values of the association constants
      disagree as a result of the difference in the experimental conditions (presence
      of salt, native protein or desalted one, approximations in the fitting of the
      data, liquid or gas phases).

PMID- 17558524
TI  - A step on the path in the discovery of new latent fingerprint development
      reagents: substituted Ruhemann's purples and implications for the law.
AB  - Energies corresponding to optimum geometries of ninhydrin, some of its analogs,
      the corresponding Ruhemann's Purple analogs and some of the intermediates of the
      reaction between ninhydrin analogs and amino acids are calculated at Hartree
      Fock/6-31G** level of theory. Such a study is significant from a forensic science
      point of view because of the strong interest in the forensic chemistry and law
      enforcement communities in developing alternatives to the current generation of
      ninhydrin-like chemicals for the detection and development of latent
      fingerprints. In examining our new predictions for the net energetics of the
      reactions in the formation of substituted Ruhemann's Purples, we find that a
      fluorine-containing analog is the most thermodynamically feasible reaction. In
      light of this finding, we suggest further experimental studies to determine the
      kinetic feasibility of synthesizing the fluorine-containing analog, as well as
      other similar molecules and to determine their spectroscopic properties.

PMID- 17558525
TI  - Molecular modeling of layered double hydroxide intercalated with benzoate,
      modeling and experiment.
AB  - The structure of Zn4Al2 Layered Double Hydroxide intercalated with
      benzencarboxylate (C6H5COO-) was solved using molecular modeling combined with
      experiment (X-ray powder diffraction, IR spectroscopy, TG measurements).
      Molecular modeling revealed the arrangement of guest molecules, layer stacking,
      water content and water location in the interlayer space of the host structure.
      Molecular modeling using empirical force field was carried out in Cerius(2)
      modeling environment. Results of modeling were confronted with experiment that
      means comparing the calculated and measured diffraction pattern and comparing the
      calculated water content with the thermogravimetric value. Good agreement has
      been achieved between calculated and measured basal spacing: d(calc) = 15.3 A and
      d(exp) = 15.5 A. The number of water molecules per formula unit (6H2O per
      Zn4Al2(OH)12) obtained by modeling (i.e., corresponding to the energy minimum)
      agrees with the water content estimated by thermogravimetry. The long axis of
      guest molecules are almost perpendicular to the LDH layers, anchored to the host
      layers via COO- groups. Mutual orientation of benzoate ring planes in the
      interlayer space keeps the parquet arrangement. Water molecules are roughly
      arranged in planes adjacent to host layers together with COO- groups.

PMID- 17558526
TI  - Chimpanzees do not take into account what others can hear in a competitive
      situation.
AB  - Chimpanzees (Pan troglodytes) know what others can and cannot see in a
      competitive situation. Does this reflect a general understanding the perceptions
      of others? In a study by Hare et al. (2000) pairs of chimpanzees competed over
      two pieces of food. Subordinate individuals preferred to approach food that was
      behind a barrier that the dominant could not see, suggesting that chimpanzees can
      take the visual perspective of others. We extended this paradigm to the auditory
      modality to investigate whether chimpanzees are sensitive to whether a competitor
      can hear food rewards being hidden. Results suggested that the chimpanzees did
      not take what the competitor had heard into account, despite being able to locate
      the hiding place themselves by the noise.

PMID- 17558527
TI  - Primary pleural hemangiopericytoma-like tumor: an unusual localized fibrous tumor
      of the pleura (2007: 4b).
AB  - In this report, the case of a 65-year-old woman with cough and dyspnoea is
      described. The chest radiographs showed a sharply demarcated mass located in the
      left paravertebral hemithorax and a left pleural effusion. Computed tomography
      after intravenous contrast material showed a heterogeneous, mainly cystic mass
      with peripheral enhancement and enhancing intratumoral foci and septa. Magnetic
      resonance imaging confirmed the location and enhancement pattern of the lesion.
      Histology following the surgical excision of the tumor showed a localized fibrous
      tumor of the pleura and specifically the hemangiopericytoma-like type.

PMID- 17558529
TI  - HCN-encoded pacemaker channels: from physiology and biophysics to bioengineering.
AB  - The depolarizing membrane ionic current I(h) (also known as I(f), "f" for funny),
      encoded by the hyperpolarization-activated cyclic-nucleotide-modulated (HCN1-4)
      channel gene family, was first discovered in the heart over 25 years ago. Later,
      I(h) was also found in neurons, retina, and taste buds. HCN channels structurally
      resemble voltage-gated K(+) (Kv) channels but the molecular features underlying
      their opposite gating behaviors (activation by hyperpolarization rather than
      depolarization) and non-selective permeation profiles (> or =25 times less
      selective for K(+) than Kv channels) remain largely unknown. Although I(h) has
      been functionally linked to biological processes from the autonomous beating of
      the heart to pain transmission, the underlying mechanistic actions remain largely
      inferential and, indeed, somewhat controversial due to the slow kinetics and
      negative operating voltage range relative to those of the bioelectrical events
      involved (e.g., cardiac pacing). This article reviews the current state of our
      knowledge in the structure-function properties of HCN channels in the context of
      their physiological functions and potential HCN-based therapies via
      bioengineering.

PMID- 17558530
TI  - Electrical activation of Na/K pumps can increase ionic concentration gradient and
      membrane resting potential.
AB  - It has been previously demonstrated by our group that our specifically designed
      synchronization modulation electric field can dynamically entrain the Na/K ATPase
      molecules, effectively accelerating the pumping action of these molecules. The
      ATPase molecules are first synchronized by the field, and subsequently their
      pumping rates are gradually modulated in a stepwise pattern to progressively
      higher and higher levels. Here, we present results obtained on application of the
      field to intact twitch skeletal muscle fibers. The ionic concentration gradient
      across the cell membrane was monitored, with the membrane potential extrapolated
      using a slow fluorescent probe with a confocal microimaging technique. The
      applied synchronization-modulation electric field is able to slowly but
      consistently increase the ionic concentration gradient across the membrane and,
      hence, hyperpolarize the membrane potential. All of these results were fully
      eliminated if ouabain was applied to the bathing solution, indicating a
      correlation with the action of the Na/K pump molecules. These results in
      combination with our previous results into the entrainment of the pump molecules
      show that the synchronization-modulation electric field-induced activation of the
      Na/K pump functions can effectively increase the ionic concentration gradient and
      the membrane potential.

PMID- 17558531
TI  - Multiple conductance substates in pharmacologically untreated Na(+) channels
      generating persistent openings in rat entorhinal cortex neurons.
AB  - Na(+)-channel activity recorded in cell-attached patches from entorhinal cortex
      neurons in the absence of gating-modifying drugs was examined to determine the
      possible occurrence of substate openings. Brief sojourns to subconductance levels
      were occasionally observed within prolonged ("persistent") burst openings.
      Subconductance occurrence and amplitude were determined following two distinct,
      complementary approaches: (1) direct visual inspection and (2) automated
      detection by application of a method that exploits the current variance of fixed
      width tracing segments to sort amplitude estimations. The two approaches led to
      comparable results. At least six subconductance levels in addition to the full
      open state were revealed, with amplitudes that were approximately 20%, 30%, 40%,
      50%, 60% and 75% that of full openings. The global probability of subconductance
      opening occurrence within a burst as well as the probability of observing one
      particular subconductance level within a burst showed no clear dependence upon
      membrane potential in the -40 to +10 mV range. Open- and closed-time
      distributions of substate openings could either be similar to those observed in
      burst full openings or show distinct patterns. Low-amplitude late openings were
      also observed in isolation, separately from full-size openings. These openings
      corresponded to conductance levels very similar to those of the substates
      observed within full-size burst openings; therefore, they were interpreted as
      isolated subconductance openings. Early, transient openings responsible for the
      fast-inactivating whole-cell Na(+)-current component also manifested distinct
      conductance levels, the two most prominent of which were in an approximate 75:100
      amplitude ratio. Interestingly, the 75% conductance level observed among early
      openings occurred much more frequently than in "persistent" burst openings. We
      conclude that pharmacologically untreated Na(+) channels from native neurons
      generate substate openings that may influence differently the multiple gating
      modes displayed by these channels.

PMID- 17558533
TI  - Development and characterization of EST-SSR markers in the eastern oyster
      Crassostrea virginica.
AB  - Simple sequence repeat (SSR) markers were developed from expressed sequence tags
      (ESTs) in the eastern oyster (Crassostrea virginica). ESTs of the eastern oyster
      were downloaded from GenBank and screened for SSRs with at least eight units of
      dinucleotide or five units of tri-, tetra-, penta-, and hexa-nucleotide repeats.
      The screening of 9101 ESTs identified 127 (1.4%) SSR-containing sequences.
      Primers were designed for 88 SSR-containing ESTs with good and sufficient
      flanking sequences. Polymerase chain reaction (PCR) amplification was successful
      for 71 primer pairs, including 19 (27%) pairs that amplified fragments longer
      than expected sizes, probably due to introns. Sixty-six pairs that produced
      fragments shorter than 800 bp were screened for polymorphism in five oysters from
      three populations via polyacrylamide gels, and 53 of them (80%) were polymorphic.
      Fifty-three polymorphic SSRs were labeled and genotyped in 30 oysters from three
      populations via an automated sequencer. Five of the SSRs amplified more than two
      fragments per oyster, suggesting locus duplication. The remaining 48 SSRs had 2
      alleles per individual, including 11 with null alleles. In the 30 oysters
      analyzed, the SSRs had an average of 9.3 alleles per locus, ranging from 2 to 24.
      Forty-three loci segregated in a family with 100 progeny, with nine showing
      significant deviation from Mendelian ratios (three after Bonferroni correction).
      Seventy percent of the loci were successfully amplified in C. rhizophorae and 34%
      in C. gigas. This study demonstrates that ESTs are valuable resources for the
      development of SSR markers in the eastern oyster, and EST-derived SSRs are more
      transferable across species than genomic SSRs.

PMID- 17558532
TI  - Leucine transport is affected by Bacillus thuringiensis Cry1 toxins in brush
      border membrane vesicles from Ostrinia nubilalis Hb (Lepidoptera: Pyralidae) and
      Sesamia nonagrioides Lefebvre (Lepidoptera: Noctuidae) midgut.
AB  - The pore-forming activity of Cry1Ab, Cry1Fa and Cry1Ca toxins and their
      interaction with leucine transport mediated by the K(+)/leucine cotransporter
      were studied in brush border membrane vesicles (BBMVs) isolated from the midgut
      of Ostrinia nubilalis and Sesamia nonagrioides. In both species, as in other
      Lepidoptera, leucine uptake by BBMVs can take place in the absence of cations,
      but it can also be driven by a K(+) gradient. Experiments with the voltage
      sensitive fluorescent dye 3,3'-diethylthiacarbocyanine iodide proved that Cry1Ab,
      a Bacillus thuringiensis toxin active in vivo, enhanced the membrane permeability
      to potassium in O. nubilalis BBMVs. This result is in agreement with similar
      effects observed in S. nonagrioides BBMV incubated with various Cry1 toxins
      active in vivo. The effect of the above toxins was tested on the initial rate of
      0.1 mM: leucine influx. Instead of an increase in leucine influx, a reduction was
      observed with the Cry1 toxins active in vivo. Cry1Ab and Cry1Fa, but not the
      inactive toxin Cry1Da, inhibited in a dose-dependent manner leucine uptake both
      in the absence and in the presence of a K(+) gradient, a clear indication that
      their effect is independent of the channel formed by the toxins and that this
      effect is exerted directly on the amino acid transport system.

PMID- 17558534
TI  - Effective metadata discovery for dynamic filtering of queries to a radiology
      image search engine.
AB  - We sought to demonstrate the effectiveness of techniques to index radiology
      images using metadata discovered in their free-text figure captions. The ARRS
      GoldMiner image library incorporated 94,256 figures from 11,712 articles
      published in peer-reviewed online radiology journals. Algorithms were developed
      to discover metadata--age, sex, and imaging modality--from the figures' free-text
      captions. Age was recorded in years, and was classified as infant (less than 2
      years), child (2 to 17 years), or adult (18+ years). Each figure was assigned to
      one of eight imaging modalities. A random sample of 1,000 images was examined to
      measure accuracy of the metadata. The patient's age was identified in 58,994
      cases (63%), and the patient's sex was identified in 58,427 cases (62%). An
      imaging modality was assigned to 80,402 (85%) of the figures. Based on the 1,000
      sampled cases, recall values for age, sex, and imaging modality were 97.2%,
      99.7%, and 86.4%, respectively. Precision values for age, sex, and imaging
      modality were 100%, 100%, and 97.2%, respectively. Automated techniques can
      accurately discover age, sex, and imaging modality metadata from captions of
      figures published in radiology journals. The metadata can be used to dynamically
      filter queries for an image search engine.

PMID- 17558535
TI  - Electrophysiological and behavioral responses of Ips duplicatus to aggregation
      pheromone in Inner Mongolia, China: amitinol as a potential pheromone component.
AB  - Volatiles from Ips duplicatus male hindgut extracts and aeration samples of
      spruce logs colonized by the virgin males were analyzed by coupled gas
      chromatography-mass spectrometry (GC-MS), coupled gas chromatography
      electroantennographic detection (GC-EAD), and field trapping bioassays in Inner
      Mongolia, China. GC-MS analyses showed that males from nuptial chambers (for
      reproduction) produced hindgut volatile profiles similar to those of maturation
      feeding males from the nonreproductive galleries. The known aggregation pheromone
      components, ipsdienol (Id) and E-myrcenol (EM) are the major constituents of this
      blend, followed by several minor bark beetle-related compounds: 2-methyl-3-buten
      2-ol, ipsenol, cis-verbenol, verbenone, 2-phenylethanol, myrtenol, and trans
      myrtanol. The enantiomeric composition of the Id from the male hindgut extracts
      was determined to be a racemic mixture (50/50) by enantioselective GC. GC-EAD
      experiments indicated that I. duplicatus antennae from both sexes responded
      strongly not only to the known aggregation pheromone components, Id and EM, but
      also to the other minor conspecific-produced compounds. The strongest antennal
      response was elicited by the major pheromone component, Id, which was ca. 2-3
      times higher than that elicited by the second component, EM. Electroantennogram
      dose-responses indicated that antennal response threshold to Id was approximately
      100 times lower than that of EM. No synergistic effects between these occurred at
      peripheral level. A strong and repeatable EAD response was found to a trace
      compound (flame ionization detection undetectable) from both hindgut and aeration
      samples. The compound was identified as amitinol (At) based on the retention time
      and a further EAD analysis of a synthetic mixture. In the field trapping
      experiments, At increased the attraction of I. duplicatus to the traps baited
      with a binary blend of EM/Id (1:1) in a synergistic manner when tested at a low
      release rate (1:1:0.1) but had no effect on catches at the high release rate
      (1:1:1). This result suggests that At might be a part of the Chinese I.
      duplicatus aggregation pheromone system. The production ratios of EM/Id from the
      Inner Mongolian population (EM/Id approximately 1:2.0-4) were twice as high as
      those reported from Europe (EM/Id approximately 1:9), corresponding well with the
      differences in the optimal response ratios.

PMID- 17558536
TI  - Foreign-language skills in rove-beetles? Evidence for chemical mimicry of ant
      alarm pheromones in myrmecophilous Pella beetles (Coleoptera: Staphylinidae).
AB  - By using chemical analyses, as well as laboratory and field behavioral tests, we
      tested the hypothesis that rove beetles of the myrmecophilous genus Pella use
      alarm pheromone compounds to avert attacks by their host ant Lasius fuliginosus.
      The secretions of Pellafunestus and P. humeralis contain quinones and different
      aliphatic compounds, mainly undecane and 6-methyl-5-hepten-2-one (sulcatone). The
      latter two chemicals are also found in L. fuliginosus pheromone glands.
      Behavioral tests confirmed that undecane serves as an "aggressive alarm"-inducing
      pheromone in L. fuliginosus, whereas sulcatone most likely is a "panic-alarm"
      inducing pheromone. The main tergal-secretion compounds, various quinones and
      undecane, individually and in mixtures induced aggression in L. fuliginosus
      workers. When sulcatone was added to these compounds, the space around the odor
      source was avoided and a reduced number of aggressive acts observed, suggesting
      that sulcatone blocks the aggression-inducing effect of undecane and the
      quinones. These results support the hypothesis that Pella beetles mimic alarm
      pheromones of their hosts. This is a rare example of chemical mimicry in
      myrmecophilous insects in which chemicals other than cuticular hydrocarbons are
      used.

PMID- 17558537
TI  - Impact of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy on
      systemic toxicity.
AB  - INTRODUCTION: The purpose of this study was to analyze the postoperative systemic
      toxicity and procedure-related mortality (PRM) of cytoreductive surgery (CRS) and
      hyperthermic intraperitoneal chemotherapy (HIPEC) in the treatment of peritoneal
      surface malignancies (PSMs). PATIENTS AND METHODS: A total of 242 (84 males/158
      females) patients with PSM underwent 247 consecutive procedures. The mean age was
      52 years (range 22-79). CRS was performed using peritonectomy procedures. The
      HIPEC technique through the closed abdomen was conducted with cisplatin (CDDP 25
      mg/m(2)/l of perfusate)+mitomycin C (MMC 3.3 mg/m(2)/l perfusate) or CDDP (43
      mg/l perfusate)+doxorubicin (Dx 15.25 mg/l perfusate) at 42.5 degrees C. These
      dosages were reduced by 30% when the patient had received systemic chemotherapy
      before the CRS+HIPEC. Systemic toxicities were graded according to the NCI CTCAE
      v3 criteria. RESULTS: G3-5 systemic toxicity rate was 11.7 % and adverse events
      were bone marrow suppression, 13; nephrotoxicity, 14; neutropenic infection, 2
      and pulmonary toxicity, 1. Independent risk factors for G3-5 systemic toxicity
      after multivariate analysis were a dose of CDDP for HIPEC of 240 mg or more (OR
      2.78, CI 95% 1.20-6.45) and CDDP+Dx schedule for HIPEC (OR 2.36, CI 95% 1.02
      5.45). PRM was 1.2%. CONCLUSIONS: CRS+HIPEC presented acceptable systemic
      toxicity and PRM rates. Independent risk factors for systemic toxicity were the
      CDDP+Dx schedule and CDDP dose for HIPEC.

PMID- 17558538
TI  - Impact of student ethnicity and primary childhood language on communication skill
      assessment in a clinical performance examination.
AB  - BACKGROUND: Clinical performance examinations (CPX) with standardized patients
      (SPs) have become a preferred method to assess communication skills in US medical
      schools. Little is known about how trainees' backgrounds impact CPX performance.
      OBJECTIVE: The objective of this paper is to examine the impact of student
      ethnicity, primary childhood language, and experience of diversity on the
      communication scores of a high-stakes CPX using SPs. DESIGN: This research was
      designed as an observational study. PARTICIPANTS: The participants of this study
      were third-year medical students at one US medical school. MEASUREMENTS AND MAIN
      RESULTS: The measurements used in this study were CPX scores from mandatory exam,
      student demographics and experience with diversity measured by self-report on a
      survey, and Medical College Admission Test (MCAT) and United States Medical
      Licensing Examination (USMLE) scores. A total of 135 students participated. Asian
      and black students scored lower than white students on the communication portion
      of the CPX by approximately half a standard deviation (Asian, 67.4%; black,
      64.4%; white, 69.4%, p < .05). There were no differences by ethnicity on
      history/physical exam scores. Multivariate analysis controlling for MCAT verbal
      scores reduced ethnic differences in communication scores (Asian-white mean
      differences = 1.95, p = 0.02), but Asian-white differences were eliminated only
      after sequential models included primary childhood language (difference = 0.57, p
      = 0.6). CONCLUSIONS: Even after controlling for English language knowledge as
      measured in MCAT verbal scores, speaking a primary childhood language other than
      English is associated with lower CPX communication scores for Asian students.
      While poorer communication skills cannot be ruled out, SP exams may contain
      measurement bias associated with differences in childhood language or culture.
      Caution is indicated when interpreting CPX communication scores among diverse
      examinees.

PMID- 17558539
TI  - Molecular characterization of the genome segments S4, S6 and S7 of rice gall
      dwarf virus.
AB  - Rice gall dwarf virus (RGDV) is a member of the genus Phytoreovirus within the
      family Reovirdae. Its genome has 12 segments of double-stranded RNA (dsRNA), of
      which the nucleotide sequences of segments S4, S6, and S7 were determined,
      providing the first complete genome sequence of RGDV. Each of the segments S4,
      S6, and S7 contained conserved terminal sequences conforming to the RGDV
      consensus, 5'-GGXA ... UGAU-3' (X = U or C). Each segment had a single predicted
      open reading frame encoding proteins with calculated molecular weights of 79.8,
      58.6, and 53.3 kDa. These proteins appeared to be homologous to those encoded by
      the corresponding segments of rice dwarf virus and wound tumor virus, the other
      known members of the same genus, having about 20-30% amino acid identity to them.
      It is therefore likely that RGDV S4 and S6 encode non-structural proteins and S7
      an inner core protein. Probable homologies between the segments of all known
      phytoreoviruses are summarized. Beyond these similarities, the RGDV proteins
      displayed no significant similarity to any other reported viral proteins.

PMID- 17558540
TI  - Identification and characterization of a new virus in the genus Potyvirus from
      wild populations of Angelica lucida L. and A. genuflexa Nutt., family Apiaceae.
AB  - A novel potyvirus was discovered in Angelica lucida L. (wild celery) and A.
      genuflexa Nutt. (kneeling Angelica) (family Apiaceae) in the Matanuska- Susitna
      Valley, Alaska. The experimental plant host range of the virus included species
      in three families: Chenopodiaceae (Chenopodium amaranticolor Coste et Reyn and
      Chenopodium quinoa Willd.), Solanaceae (Nicotiana benthamiana Domin, and N.
      clevlandii Gray.), and Apiaceae (Anethum graveolens L., Apium graveolens L. var.
      dulce (Miller)), Daucus carota L. subspecies sativus (Hoffm.) Arcang., and
      Petroselinum crispum (Miller) Nyman ex A. W. Hilland). The virus contained
      flexuous rods with an ssRNA genome approximately 9.5-10 k nts and a CP (
      approximately 35 kDa) that reacted to a universal potyvirus monoclonal antibody
      in Western blot analysis. The sequenced genomic 3'-end ( approximately 1850 nt)
      contained a potyvirus genomic arrangement that included the 3'-terminus of the
      NIb (nuclear inclusion) gene, the CP (coat protein) gene, and a 3'-UTR
      (untranslated region) attached to a poly(A)tail. The CP amino acids had between
      54 and 70% identity with 12 selected members from the genus Potyvirus.
      Phylogenetically, the Alaskan potyvirus clustered with three other apiaceous
      potyviruses from Australia. The novel Alaskan virus was confined to A. lucida L.
      and A. genuflexa Nutt. in nature, and was classified in the genus Potyvirus,
      family Potyviridae, and in part named after its natural plant hosts, angelica
      virus Y (AnVY).

PMID- 17558541
TI  - Analysis of the PB2 gene reveals that Indian H5N1 influenza virus belongs to a
      mixed-migratory bird sub-lineage possessing the amino acid lysine at position 627
      of the PB2 protein.
AB  - Outbreaks of highly pathogenic avian influenza (HPAI) H5N1 virus were reported
      for the first time in India during February 2006. Herein, we have sequenced and
      analyzed the PB2 genes of five influenza virus isolates obtained from three
      affected states (Gujarat, Madhya Pradesh and Maharashtra) in India during the
      outbreaks. In the phylogenetic analysis, the Indian isolates were grouped in the
      mixed-migratory bird sub-lineage of the Eurasian lineage. From the phylogenetic
      tree, it is evident that viruses were probably introduced to India from China via
      Europe because they share a direct ancestral relationship with the Indian
      isolates. The virus might have spread through migratory waterfowls that survived
      the HPAI H5N1 infection. These viruses were able to replicate in cultured cells
      of avian and mammalian hosts and posses lysine at position 627 of the PB2
      protein, indicating that they might be able to cross the host barrier to infect
      mammals.

PMID- 17558542
TI  - Genetic heterogeneity of Russian, Estonian and Finnish field rabies viruses.
AB  - Thirty-five field rabies virus strains were collected in recent years in
      different regions of the Russian Federation in order to characterize their
      genetic heterogeneity and to study their molecular epidemiology. In addition to
      the Russian viruses, seven archive samples from Estonia and Finland and two
      Russian vaccine strains were also included in the study. The viruses collected
      were subjected to two different reverse transcription-polymerase chain reaction
      tests, the amplicons were sequenced and the sequences were analysed
      phylogenetically. Among the field viruses studied, two main phylogenetic groups
      were found and designated as Pan-Eurasian and Caucasian according to their
      geographic origin. The Pan-Eurasian group, comprising some reference viruses from
      Europe, was further divided into four subgroups. All of the vaccine strains were
      clearly different from the field strains. No recombination between the field and
      vaccine virus strains was observed. The data obtained here show the critical role
      of geographical isolation and limitation for the genetic clustering and evolution
      of the rabies virus and also help in predicting its distribution from rabies
      affected areas to rabies-free areas.

PMID- 17558543
TI  - Identification of the major protein components of rice egg cells.
AB  - The female gamete, the egg cell, is a specially differentiated haploid cell that
      develops into an embryo following fertilization. In the present study, we
      analyzed egg cell lysates by sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis and subsequent mass spectrometry-based proteomics technology and
      identified the major proteins expressed in rice egg cells. The proteins
      identified included glyceraldehyde-3-phosphate dehydrogenase, ascorbate
      peroxidase and heat shock protein 90. The abundant existence of chaperons and
      antioxidant enzymes in plant egg cells indicates that the major protein
      components of plant egg cells are partly analogous to those of mammalian eggs and
      oocytes.

PMID- 17558544
TI  - Inherited maternal effects on the drought tolerance of a natural hybrid aquatic
      plant, Potamogeton anguillanus.
AB  - We tested whether maternal effects have led to the adaptive divergence of strains
      of the natural hybrid Potamogeton anguillanus, whose putative parents show
      contrastingly divergent ecologies. To examine the correlation between phenotypic
      characters and maternal types, we conducted drought experiments and DNA typing
      using nuclear and chloroplast genes. In the field, we investigated the
      distribution of the maternal type along the depth and the inshore-offshore
      gradient. Hybrids of P. malaianus mothers (M-hybrids) and those of P. perfoliatus
      mothers (P-hybrids) could not be distinguished morphologically under submerged
      conditions, but differed in drought tolerance. M-hybrids and P. malaianus formed
      more terrestrial shoots and exhibited higher survival than P-hybrids and P.
      perfoliatus in drought experiments. The distribution survey clarified that M
      hybrids were dominant in shallow and inshore areas, whereas they were almost
      absent in deeper and offshore areas. These results indicate that the natural
      hybrid P. anguillanus differs in adaptive values depending on the maternal type.
      Bidirectional hybridization and heritable maternal effects may have played
      important roles in its phenotypic adaptation to local environmental conditions.

PMID- 17558545
TI  - Multiple dextranases from the yeast Lipomyces starkeyi.
AB  - The soil yeast Lipomyces starkeyi (NCYC 1436) secretes dextranase activity into
      the growth medium. Resolution of a dextranase-active protein fraction by SDS-PAGE
      produced three protein bands, of 66 kDa, 68 kDa and 78 kDa, and isoelectric
      focusing of the same fraction resulted in seven protein bands, of pIs 3.50, 3.85,
      4.20, 4.80, 4.85, 5.00 and 5.30. Dextranase activity was demonstrated for all the
      isoelectric forms, and for the 78 kDa species in the presence of SDS. Amino acid
      compositions of the 66 kDa, 68 kDa and 78 kDa protein bands were determined, and
      the N-termini of the 66 kDa and 78 kDa protein bands were sequenced: the first
      two amino acids at the N-terminus of each protein were alanine and valine,
      respectively; an alanine-valine pair is seen early in the N-terminal coding
      sequences of the dextranases and the isopullulanase produced by the
      phylogenetically disparate organisms contributing to glycosyl hydrolase family
      49.

PMID- 17558546
TI  - Streptomyces tritolerans sp. nov., a novel actinomycete isolated from soil in
      Karnataka, India.
AB  - A Gram-positive, nonmotile, moderately halophilic, alkali and thermotolerant
      strain designated DAS 165(T), was isolated from a dry land soil sample from the
      Gulbarga region, Karnataka province, India. The isolate produced yellow substrate
      mycelia and gray aerial mycelia on most tested media. Strain DAS 165(T) showed
      growth in the presence of 5 to 7% NaCl and at 45 degrees C. The DNA G + C content
      was 69.7%. 16S rRNA gene sequence analysis together with these characteristics
      consistently assigned strain DAS 165(T) to the genus Streptomyces. The 16S rRNA
      gene sequence analysis revealed that strain DAS 165(T) was most closely related
      to S. tendae ATCC 19812(T) (D 63873) with a sequence similarity of 99.6% (three
      nucleotide differences out of 1,517). Strain DAS 165(T) formed a distinct clade
      based on analysis of the almost complete sequence and 120-nucleotide variable
      gamma region of the 16S rRNA gene. Despite the high sequence similarity, strain
      DAS 165(T) was phenotypically different from S. tendae ATCC 19812(T). DNA-DNA
      hybridization between these strains was 47% showing that strain DAS 165(T) is a
      distinct genomic species. Phenetic and genetic results support the classification
      of strain DAS 165(T) as a new species, for which the name S. tritolerans is
      proposed, with strain DAS 165(T) as the type strain (=DSM 41899(T )= CCTCCAA
      206013(T)).

PMID- 17558547
TI  - Gene arrangements characteristic of the phylum Actinobacteria.
AB  - The availability of genomic sequence data allows new challenges to various
      biological problems. One of such attempts is the extraction of phylogenetic
      information from gene order data of genomes. Phylogenetic inferences are most
      commonly carried out on the basis of 16S rRNA trees, which sometimes produce
      unresolved or unreliable branching orders. One example for such a low resolution
      is recognized in the branching pattern among the phylum Actinobacteria. Here,
      gene arrangements characteristic of the Actinobacteria were identified, based on
      which Symbiobacterium thermophilum is phylogenetically placed outside that
      phylum, this being in contrast to 16S rRNA trees and to the current taxonomy in
      GenBank. Three transposition suggestive arrangements were found which support a
      notion that Rubrobacter xylanophilus is the earliest diverging species among the
      completely sequenced Actinobacteria. The gene arrangements identified here serve
      as a complement to previously reported indels and proteins characteristic of this
      phylum.

PMID- 17558551
TI  - Pathogen specific carbohydrate antigen microarrays: a chip for detection of
      Salmonella O-antigen specific antibodies.
AB  - A Salmonella O-antigen microarray was developed by covalent coupling of
      oligosaccharide antigens specific for serogroups Salmonella enterica sv.
      Paratyphi (group A), Typhimurium (group B) and Enteritidis (group D). Antibodies
      were correctly detected in sera from patients with culture verified
      salmonellosis. High serogroup-specificity was seen with the disaccharide
      antigens. With the larger antigens, containing the backbone sequence Manalpha1
      2Rhaalpha1-2Gal (MRG), common backbone-specific antibodies (O-antigen 12) were
      also detected. This is "proof of principle" that pathogen-specific carbohydrate
      antigen microarrays constitute a novel technology for rapid and specific
      serological diagnosis in either individual patients or larger sero
      epidemiological and vaccine studies.

PMID- 17558548
TI  - Chloroplast envelope membranes: a dynamic interface between plastids and the
      cytosol.
AB  - Chloroplasts are bounded by a pair of outer membranes, the envelope, that is the
      only permanent membrane structure of the different types of plastids.
      Chloroplasts have had a long and complex evolutionary past and integration of the
      envelope membranes in cellular functions is the result of this evolution. Plastid
      envelope membranes contain a wide diversity of lipids and terpenoid compounds
      serving numerous biochemical functions and the flexibility of their biosynthetic
      pathways allow plants to adapt to fluctuating environmental conditions (for
      instance phosphate deprivation). A large body of knowledge has been generated by
      proteomic studies targeted to envelope membranes, thus revealing an unexpected
      complexity of this membrane system. For instance, new transport systems for
      metabolites and ions have been identified in envelope membranes and new routes
      for the import of chloroplast-specific proteins have been identified. The picture
      emerging from our present understanding of plastid envelope membranes is that of
      a key player in plastid biogenesis and the co-ordinated gene expression of
      plastid-specific protein (owing to chlorophyll precursors), of a major hub for
      integration of metabolic and ionic networks in cell metabolism, of a flexible
      system that can divide, produce dynamic extensions and interact with other cell
      constituents. Envelope membranes are indeed one of the most complex and dynamic
      system within a plant cell. In this review, we present an overview of envelope
      constituents together with recent insights into the major functions fulfilled by
      envelope membranes and their dynamics within plant cells.

PMID- 17558552
TI  - Mediators of the development and prevention of violent behavior.
AB  - The purpose of this investigation was to determine if the Aban Aya Youth Project,
      a culturally grounded intervention, produced differences in changes over time in
      core intervening variables (i.e., communal value orientation, empathy, violence
      avoidance efficacy beliefs) and whether these variables mediated intervention
      effects on the development of youth violent behavior. Fifth grade cohorts at 12
      schools were randomly assigned to one of two intervention conditions or an
      attention placebo control condition and followed longitudinally through eighth
      grade. A total of 668 students (49% male) participated in the study. Mediation
      analyses suggested that both program conditions (as compared to the control
      condition) led to steeper increases over time in empathy which, in turn were
      related to reductions in the likelihood of violent behavior over time. No other
      significant program effects were detected, although changes over time in violence
      avoidance efficacy were associated with reduced likelihood of violent behavior.
      Findings are discussed in terms of theory development, program development and
      points of refinement of the Aban Aya Youth Project and implications for future
      research.

PMID- 17558553
TI  - Acculturating Indian immigrant men in New York City: applying the social capital
      construct to understand their experiences and health.
AB  - This study qualitatively explored social capital available to individuals (N =
      17) within a community-based purposive sample of adult male immigrants from India
      in New York City (NYC). Analysis of in-depth interview data identified possible
      pathways for social capital's influences upon acculturative stress. The study
      defined social capital in terms of the participants' social relationships among
      peers, in the workplace, and with their ethnic community. Their relationships
      were assessed in terms of support, trust, and reciprocity. Among the recent
      immigrants, hopelessness and frustration about future work prospects were
      associated with symptoms of depression and substance abuse. The participants
      identified wealth as a distinct marker of social class and they described social
      class as a combination of education and occupation. Social class largely
      determined the particular peer and community networks each participant joined.
      Participants relied upon ongoing connections with family in India, despite their
      geographic separation, to relieve acculturative stress. Social support from peers
      was the participants' most useful and immediate resource for alleviating
      acculturative stress. For participants of lower socioeconomic status,
      acculturative stress was compounded by social-relationship expectations and norms
      from India that persisted within NYCs immigrant community. Namely, lower-SES
      participants were more likely to experience frustration and setbacks when they
      sought out intimate social relationships with women.

PMID- 17558554
TI  - Reliability of estimating stochastic lung tissue heterogeneity from pulmonary
      impedance spectra: a forward-inverse modeling study.
AB  - Heterogeneity of regional lung mechanics is an important determinant of the work
      of breathing and may be a risk factor for ventilator associated lung injury. The
      ability to accurately assess heterogeneity may have important implications for
      monitoring disease progression and optimizing ventilator settings. Inverse
      modeling approaches, when applied to dynamic pulmonary impedance data (Z(L)), are
      thought to be sensitive to the detection of mechanical heterogeneity with the
      ability to characterize global lung function using a minimal number of free
      parameters. However, the reliability and bias associated with such model-based
      estimates of heterogeneity are unknown. We simulated Z(L) spectra from healthy,
      emphysematous, and acutely injured lungs using a computer-generated anatomic
      canine structure with asymmetric Horsfield branching and various predefined
      distributions of stochastic lung tissue heterogeneity. Various inverse models
      with distinct topologies incorporating linear resistive and inertial airways with
      parallel tissue viscoelasticity were then fitted to these Z(L) spectra and
      evaluated in terms of their quality of fit as well as the accuracy and
      reliability of their respective model parameters. While all model topologies
      detected appropriate changes in tissue heterogeneity, only a topology consisting
      of lumped airway properties with distributed tissue properties yielded accurate
      estimates of both mean lung tissue stiffness and the spread of regional
      elastances. These data demonstrate that inverse modeling approaches applied to
      noninvasive measures of Z(L) may provide reliable and accurate assessments of
      lung tissue heterogeneity as well as insight into distributed lung mechanical
      properties.

PMID- 17558555
TI  - Community-wide strategies for preventing homelessness: recent evidence.
AB  - This article summarizes the findings of a study of community-wide strategies for
      preventing homelessness among families and single adults with serious mental
      illness, conducted for the US Department of Housing and Urban Development. The
      study involved six communities, of which this article focuses on five. A major
      finding of this study was that it was difficult to identify sites with community
      wide strategies, and even harder to find any that maintained data capable of
      documenting prevention success. However, the five communities selected for this
      study presented key elements of successful strategies including mechanisms for
      accurate targeting, a high level of jurisdictional commitment, significant
      mainstream agency involvement, and mechanisms for continuous system improvement.

PMID- 17558559
TI  - Human sulfatases: a structural perspective to catalysis.
AB  - The sulfatase family of enzymes catalyzes hydrolysis of sulfate ester bonds of a
      wide variety of substrates. Seventeen genes have been identified in this class of
      sulfatases, many of which are associated with genetic disorders leading to
      reduction or loss of function of the corresponding enzymes. Amino acid sequence
      homology suggests that the enzymes have similar overall folds, mechanisms of
      action, and bivalent metal ion-binding sites. A catalytic cysteine residue,
      strictly conserved in prokaryotic and eukaryotic sulfatases, is post
      translationally modified into a formylglycine. Hydroxylation of the formylglycine
      residue by a water molecule forming the activated hydroxylformylglycine (a
      formylglycine hydrate or a gem-diol) is a necessary step for the enzyme's
      sulfatase activity. Crystal structures of three human sulfatases, arylsulfatases
      A and B(ARSA and ARSB), and estrone/dehydroepiandrosterone sulfatase or steroid
      sulfatase (STS), also known as arylsulfatase C, have been determined. While ARSA
      and ARSB are water-soluble enzymes, STS has a hydrophobic domain and is an
      integral membrane protein of the endoplasmic reticulum. In this article, we
      compare and contrast sulfatase structures and revisit the proposed catalytic
      mechanism in light of available structural and functional data. Examination of
      the STS active site reveals substrate-specific interactions previously identified
      as the estrogen-recognition motif. Because of the proximity of the catalytic
      cleft of STS to the membrane surface, the lipid bilayer has a critical role in
      the constitution of the active site, unlike other sulfatases.

PMID- 17558560
TI  - The Dim protein family: from structure to splicing.
AB  - The spliceosome is a dynamic macromolecular machine that catalyzes pre-mRNA
      splicing through a mechanism controlled by several accessory proteins, including
      the Dim proteins. The Dim protein family is composed of two classes, Dim1 and
      Dim2, which share a common thioredoxin-like fold. They were originally identified
      for their role in cell cycle progression and have been found to interact with
      Prp6, an essential component of the spliceosome, which forms the bridge of
      U4/U6.U5-tri-snRNP. In spite of their biological and structural similarities,
      Dim1 and Dim2 proteins differ in many aspects. Dim1 bears distinctive structural
      motifs responsible for its interaction with other spliceosome components. Dim2
      forms homodimers and contains specific domains required for its interactions with
      partners. This originality suggests that although both proteins are involved in
      pre-mRNA splicing, they are likely to be involved in different biological
      pathways. In the present article we review the structure and function of the Dim
      proteins.

PMID- 17558561
TI  - The death receptor DR5 is involved in TRAIL-mediated human osteoclast apoptosis.
AB  - The number and activity of osteoclasts (OCs) are critical for maintaining normal
      bone turnover. The number is determined by the rates of cell differentiation and
      death. TNF-related apoptosis-inducing ligand (TRAIL), a member of the TNF
      superfamily, induces apoptosis by interacting with its death receptors, (DR4,
      DR5). However, its activity can be modulated by two decoy receptors, (DcR1 and
      DcR2). In this paper we show that TRAIL treatment causes reduced OC viability as
      well as an increased apoptotic OC number. Loss of nuclei integrity and
      derangement of the actin microfilament were also induced by TRAIL in OCs.
      Moreover, we demonstrated the expression of all TRAIL receptors in both
      precursors and differentiated OCs, and the upregulation of DR5 during OC
      differentiation. Interestingly, DcR2 was upregulated in the early stage of
      osteoclastogenesis and downregulated at the end of the differentiation process.
      We showed that DR5, upregulated by TRAIL, could be the mediator of TRAIL-induced
      OC apoptosis, since the addition of anti-DR5 neutralizing antibodies restores the
      OC viability previously reduced by TRAIL. Furthermore, the intracellular pathway
      induced by TRAIL in OCs involves caspase-8 and Bid activation. In conclusion, our
      data highlight an important role for the TRAIL/TRAIL receptor system in the
      regulation of OC apoptosis.

PMID- 17558574
TI  - Determining the efficacy of Dementia Care Mapping as an outcome measure and a
      process for change: a pilot study.
AB  - Dementia Care Mapping (DCM) is increasingly being promoted world-wide as a useful
      approach in assisting staff to improve the well-being of residents with dementia.
      While DCM is employed as an outcome measure of well-being and as a process to
      assist staff improve quality of care, it has not been subject to the rigorous
      scrutiny of a controlled trial to establish its efficacy as an outcome measure,
      or as an intervention. In 2005 the authors were awarded an Australian Health
      Minister's Grant to conduct a randomised control trial of DCM in 15 residential
      dementia care units across the city of Sydney, Australia. This paper reports on a
      pilot study conducted with 35 dementia care residents in three secure residential
      care units in the state of New South Wales, Australia, prior to the controlled
      trial. The main aims of the pilot were to determine the sensitivity of DCM
      against the validated baseline and outcome measures selected for the trial and to
      evaluate the utility of the research plan. The utility of the research plan was
      established. Whilst a significant improvement was shown in staff interactions
      with residents over time, there was no evidence that DCM improved the residents'
      quality of life and well-being in relation to physical and cognitive functioning,
      although there was a reduction in the residents' levels of agitation and
      depression. While as a research tool DCM needs further refinement to match the
      strength of validated outcome measures that more accurately assess the residents'
      well-being, DCM procedures improved staff's attention to monitoring and attending
      to the residents' well-being.

PMID- 17558562
TI  - Isolation and characterization of expressed sequence tags (ESTs) from subtracted
      cDNA libraries of Pennisetum glaucum seedlings.
AB  - Pearl millet (Pennisetum glaucum), used as forage and grain crop is a stress
      tolerant species. Here we identify differentially regulated transcripts in
      response to abiotic (salinity, drought and cold) stresses from subtracted cDNA
      libraries by single-pass sequencing of cDNA clones. A total of 2,494 EST
      sequences were clustered and assembled into a collection of 1,850 unique
      sequences with 224 contigs and 1,626 singleton sequences. By sequence comparisons
      the putative functions of many ESTs could be assigned. Genes with stress related
      functions include those involved in cellular defense against abiotic stresses and
      transcripts for proteins involved in stress response signaling and transcription
      in addition to ESTs encoding unknown functions. These provide new candidate genes
      for investigation to elucidate their role in abiotic stress. The relative mRNA
      abundance of 38 selected genes, quantified using real time quantitative RT-PCR,
      demonstrated the existence of a complex gene regulatory network that
      differentially modulates gene expression in a kinetics-specific manner in
      response to different abiotic stresses. Notably, housekeeping and non-target
      genes were effectively reduced in these subtracted cDNA libraries constructed.
      These EST sequences are a rich source of stress-related genes and reveal a major
      part of the stress-response transcriptome that will provide the foundation for
      further studies into understanding Pennisetum's adaptability to harsh
      environmental conditions.

PMID- 17558564
TI  - Disruption of the neurokinin-3 receptor (NK3) in mice leads to cognitive
      deficits.
AB  - RATIONALE: The structurally related neuropeptides, substance P, neurokinin A, and
      neurokinin B, belong to a family of molecules termed tachykinins and are widely
      distributed in the central and peripheral nervous systems. These peptides mediate
      their effects through three G protein coupled receptor subtypes, the neurokinin
      1, neurokinin-2 and neurokinin-3 receptors, respectively. OBJECTIVE: To study the
      physiological functions of NK3, a line of NK3 knockout mice were generated and
      characterized in a broad spectrum of well-established behavioral tests. RESULTS:
      In several tests, including spontaneous locomotor activity, elevated plus maze,
      forced swim, and hot plate, wild-type and knockout mice performed similarly.
      However, in several cognition tests, including passive avoidance, acquisition of
      conditioned avoidance responding (CAR), and the Morris water maze, NK3 knockout
      mice displayed deficits compared to wild-type mice. Although NK3 wild-type and
      knockout mice performed similarly in the training phase of the passive avoidance
      test, knockout mice had shorter latencies to enter the dark compartment on days 3
      and 4, suggesting impaired retention. In the acquisition phase of the conditioned
      avoidance responding assay, NK3 knockout mice acquired the CAR task at a slower
      rate than wild-type mice. Once the CAR test was acquired, both NK3 wild-type and
      knockout mice responded similarly to clozapine and risperidone, drugs which
      suppress responding in this test. In the Morris water maze, NK3 knockout mice
      showed increased latencies to find the escape platform on day 3 of training,
      suggesting a modest, but significant delay in acquisition compared to wild-type
      mice. CONCLUSION: These studies suggest a role for NK3 in learning and memory in
      mice.

PMID- 17558575
TI  - Inappropriate treatment of people with dementia in residential and day care.
AB  - Dependence on the help provided by other people increases the risk of a person
      being inappropriately treated. Our objective was to investigate inappropriate
      treatment and its context in the care of people with dementia. Some 85 clients
      across eight care units providing dementia care were observed by means of a
      structured Dementia Care Mapping method (DCM). Of the 17 DCM categories for
      inappropriate treatment, withholding, invalidation, and objectification were the
      categories coded most frequently. Inappropriate treatment episodes were mostly
      associated with eating and situations in which a client had a need or request.
      Most episodes occurred accidentally. The results show that nurses involved in
      dementia care need more knowledge of how illnesses causing dementia change the
      way the affected person experiences reality, and of the ethical aspects of their
      work.

PMID- 17558576
TI  - Measurement and analysis of behavioural disturbance among community-dwelling and
      institutionalized persons with dementia.
AB  - Census data suggest that persons over 84 years of age represent the fastest
      growing segment of populations in most western nations. As advancing age remains
      the single strongest risk factor for dementia, prevalence rates are expected to
      increase substantially in coming years. This awareness underscores the need to
      more fully understand the clinical presentation of Alzheimer disease and other
      neurodegenerative disorders. The present study examines responses to the 28-item
      Dementia Behaviour Disturbance Scale (DBD; Baumgarten, Becker, & Gauthier, 1990)
      among a national sample of persons with dementia (PWD) in Canada. A 3-factor
      solution appears to best reflect DBD responses for both institutionalized and
      community-dwelling PWD. This finding is notable given that the former was
      significantly more impaired and presented with significantly greater levels of
      behavioural disturbance. Support for the factorial validity of these constructs
      is provided relative to caregiver burden and depressive symptomatology. Of note,
      only 14 of 28 DBD items were retained in our analyses; on this basis, we propose
      the use of an abridged version of the scale. These findings can be generalized
      with greater confidence given the random and representative nature of the PWD and
      caregiver samples.

PMID- 17558577
TI  - Initial psychometrics of the ambiance scale: a tool to study person-environment
      interaction in dementia.
AB  - Our purpose was to evaluate the psychometric properties of the Ambiance Scale
      (AS), a new instrument that assesses the capacity of long-term care environments
      for generating affective and behavioural responses in people with dementia.
      Within the context of three parent studies of dementia-related behaviour in long
      term care settings, we conducted a cross-sectional correlational study by
      creating two separate samples of ratings from among all those available. Factor
      analysis revealed a two-factor structure (engaging, soothing) for the AS.
      Internal consistency and evaluation of inter- and intra-rater reliability were
      favourable. A consistent pattern of ratings on the AS and its subscales, moderate
      subscale correlations, and significant differences between facility types:
      nursing homes (NH) vs assisted living facilities (ALF) and among selected
      locations (residents' rooms, dining rooms, halls) within facility types support
      construct validity of the scale.

PMID- 17558578
TI  - It's all in the details: physician variability in disclosing a dementia
      diagnosis.
AB  - This study explored physician opinion about how to disclose a dementia diagnosis.
      Qualitative analysis was used to examine group and individual variability
      regarding the philosophy about and pragmatics of disclosure in a sample of
      physicians experienced with dementia. While all clinicians believed they should
      disclose a dementia diagnosis, there was wide variability in what 'disclosure'
      meant to them. Even individual physicians said their disclosure strategy differs
      from patient to patient depending on the specifics of each case. Variability was
      seen in attitudes about when and to whom they disclose a dementia diagnosis, who
      should deliver the news, what language is used, and what topics are covered. Each
      physician seemed to apply an idiosyncratic and complex algorithm to make
      decisions about these process features of the conversation. They weigh shifting
      perceptions of the utility of disclosure in conjunction with a desire to
      facilitate care planning, an awareness of family dynamics, a responsibility to
      acknowledge preferences, and an obligation to communicate clear information, all
      within the time constraints of a medical consultation. Further empirical research
      is needed to establish best practices that promote psychological adjustment and
      successful disease management in patients and caregivers who receive a dementia
      diagnosis.

PMID- 17558579
TI  - Emotional impact of dementia diagnosis: exploring persons with dementia and
      caregivers' perspectives.
AB  - This paper examined the emotional impact of diagnosis disclosure on recently
      diagnosed people with dementia. Thirty patient/caregiver dyads attending a
      Geriatric Day Hospital Program in Ottawa, Canada participated in this qualitative
      exploratory study. Data sources included: (a) audio-tapes of diagnosis disclosure
      meeting, (b) in-depth interviews with patients and caregivers within one week of
      disclosure, and (c) focus group interviews with caregivers within one month.
      Patients exhibited a range of emotional responses which can be divided into three
      broad categories: (a) responses suggesting a lack of insight and/or an active
      denial of the diagnosis, (b) grief reactions/emotional crisis related to the
      experience of actual or anticipated losses associated with dementia, and (c)
      positive coping responses to maximize the disease outcome. Participants went
      through stages of emotional response to their diagnosis: not noticing symptoms,
      noticing & covering up, or noticing & revealing; diagnostic process & disclosure;
      confirming or shock; denial, crisis, or maximizing; disorganization or
      adaptation. There is a need to develop a better understanding of the experience
      of people with dementia at the critical point of diagnosis disclosure in order to
      design supportive interventions to maximize adaptive coping responses.

PMID- 17558580
TI  - The effects of reminiscence on psychological well-being in older adults: a meta
      analysis.
AB  - This paper presents the results of a meta-analysis to assess the effectiveness of
      reminiscence on psychological well-being across different target groups and
      treatment modalities. Fifteen controlled outcome studies were included. An
      overall effect size of 0.54 was found, indicating a moderate influence of
      reminiscence on life-satisfaction and emotional well-being in older adults. Life
      review was found to have significantly greater effect on psychological well-being
      than simple reminiscence. In addition, reminiscence had significantly greater
      effect on community-dwelling adults than adults living in nursing homes or
      residential care. Other characteristics of participants or interventions were not
      found to moderate effects. It is concluded that reminiscence in general, but
      especially life review, are potentially effective methods for the enhancement of
      psychological well-being in older adults. However, a replication of effectiveness
      studies of the well-defined protocols is now warranted.

PMID- 17558581
TI  - Gender-specific and gender-sensitive associations with psychological health and
      morbidity in older age. Baseline findings from a British population survey of
      ageing.
AB  - OBJECTIVE: To examine gender-specific and gender-sensitive factors associated
      with psychological health and morbidity. DESIGN: Face-to-face home interview
      survey of random sample of 999 people aged 65 and over living in Britain.
      RESULTS: A fifth of respondents had symptoms of psychological morbidity. Men with
      high self-efficacy had over six times the odds of men with lower levels, of
      scoring as a non-case with the 12-item General Health Questionnaire (GHQ-12).
      Women with excellent to good health status had over five times the odds of those
      in worse health of scoring as a non-case. Self-efficacy and mobility were the
      strongest independent predictive variables of GHQ score among men; health status
      and subjective QoL were the strongest, independent predictors among women.
      DISCUSSION: This paper is unique in examining in detail the independent, gender
      specific and gender-sensitive predictors of psychological morbidity in a national
      random sample of older adults. Optimism, self-efficacy, quality of life and
      mobility were gender-specific predictors, and health status was a gender
      sensitive predictor of psychological morbidity. These differences suggest that
      interventions aiming to improve the mental health outcomes of older people need
      to be guided by evidence on risk factors by gender.

PMID- 17558582
TI  - Comparison of depressive symptoms between homebound older adults and ambulatory
      older adults.
AB  - Due to the social isolation imposed by chronic illness and functional
      limitations, homebound older adults are more vulnerable to depression than their
      mobility-unimpaired peers. In this study, we compared 81 low-income homebound
      older adults, aged 60 and older, with their 130 ambulatory peers who attended
      senior centers, with respect to their depressive symptoms, depression risk and
      protective factors, and self-reported coping strategies. Even controlling for
      sociodemographics, health problems, and other life stressors, being homebound, as
      opposed to participating in senior centers, was significantly associated with
      higher depressive symptoms. However, when the coping resources-social support and
      engagement in frequent physical exercise, in particular-were added to the
      regression model, the homebound state was no longer a significant factor, showing
      that the coping resources buffered the effect of the homebound state on
      depressive symptoms. In terms of self-reported coping strategies, even among the
      depressed respondents, only a small proportion sought professional help, and that
      was largely limited to consulting their regular physician and social workers, who
      may not have had professional training in mental health interventions.

PMID- 17558583
TI  - Predictors of burden and depression among nursing home family caregivers.
AB  - This study identified predictors of caregiver burden and depression among family
      caregivers to nursing home residents. Pearlin's stress process model was used as
      a theoretical framework. Structured interviews were conducted with 103 family
      caregivers to nursing home residents. Multiple regression analysis was used to
      determine the relationship of contextual variables (caregiver age, income,
      health), caregiving stressors (resident's memory and behaviour problems,
      caregiving tasks, satisfaction with nursing home), and social support with
      caregiver burden and depression. All three domains of predictor variables were
      significantly related to caregiver burden. Only contextual factors and social
      support predicted depression. Depression levels were elevated in this sample,
      with the mean falling above the cutoff for clinical depression. Family members of
      nursing home residents are at risk for caregiver burden and depression and each
      outcome has unique predictors in this population. Understanding factors
      associated with greater burden and depression can guide nursing home staff and
      mental health professionals in working with family members. Older family members,
      those in poor physical health or with low incomes are at highest risk,
      particularly for depression; while families of more impaired residents are at
      higher risk for burden. Social support is an important factor in alleviating
      burden and promoting positive mental health.

PMID- 17558584
TI  - An investigation of long-term effects of group music therapy on agitation levels
      of people with Alzheimer's Disease.
AB  - This study aimed to investigate the long-term effects of group music therapy on
      agitation manifested by nursing home residents with Alzheimer's disease. A non
      randomised experimental design was employed with one group receiving weekly music
      therapy (n = 26) and another group receiving standard nursing home care (n = 19).
      Agitation levels were measured five times over one year using the Cohen-Mansfield
      Agitation Inventory (Cohen-Mansfield, J. (1989). Agitation in the elderly. In N.
      Billig & P. V. Rabins (Eds.), Issues in geriatric psychiatry (pp. 101-113).
      Basel, Switzerland: Karger). Although music therapy participants showed short
      term reductions in agitation, there were no significant differences between the
      groups in the range, frequency, and severity of agitated behaviours manifested
      over time. Multiple measures of treatment efficacy are necessary to better
      understand the long-term effects music therapy programs have on this population.

PMID- 17558585
TI  - Symptoms of psychosis and depression in middle-aged and older adults with
      psychotic disorders: the role of activity satisfaction.
AB  - The presence of depressive symptoms among patients with psychosis is well
      documented in the literature. Behavioral models of depression emphasize the role
      of environmental factors in the onset and maintenance of depressive symptoms. The
      purpose of this study was to examine the efficacy of an activity-buffering model
      of well-being, in which increased satisfaction with leisure activities serves to
      moderate the relationship between symptoms of psychosis and multiple measures of
      well-being. Participants were 210 middle-aged and older adults with a diagnosis
      of schizophrenia or schizoaffective disorder. Analyses examined the main and
      interactive effects of positive symptoms, negative symptoms, and activity
      satisfaction for predicting both depressive symptoms and overall well-being.
      Results indicated that when individuals were less satisfied with their leisure
      activities, the relationship between negative symptoms and depressive symptoms
      was significant (p < 0.001). However, when individuals had high satisfaction,
      negative symptoms and depressive symptoms were no longer related (p = 0.243).
      Similar results were observed for overall well-being. These results provide
      initial support for an activity-buffering model of well-being among middle-aged
      and older patients with psychosis. Behavioral therapies which encourage
      engagement in reinforcing activities may provide additional benefits to existing
      treatments for psychosis, including reduced depression, improved well-being, and
      possibly functional outcomes.

PMID- 17558586
TI  - Mindfulness-based cognitive therapy for recurring depression in older people: a
      qualitative study.
AB  - Mindfulness-based Cognitive Therapy (MBCT) is a meditation-based intervention
      designed to reduce recurrence in people with histories of relapsing unipolar
      major depression. MBCT is an eight-session course delivered to groups of
      participants who are currently not (or only mildly) depressed. We sought to
      determine whether MBCT is suitable for older people, and what modifications they
      may require. We recruited 38 participants aged over 65, of whom 30 completed an
      MBCT course. Their responses at assessment, post-course and one-year follow-up
      interviews, plus comments at three-monthly 'reunion' meetings, provided data for
      thematic analysis. Main themes emerging for participants as a group are
      considered, as are individuals' understandings and uses of MBCT, and how these
      developed during and following the course. We found MBCT promising as a cost
      effective addition to clinicians' repertoire for addressing depression in old
      age, and identified issues for further research. Participants' comments indicated
      that they considered MBCT a helpful intervention for older sufferers from
      recurring depression.

PMID- 17558587
TI  - Y chromosome variation in Europe: continental and local processes in the
      formation of the extant gene pool.
AB  - The polymorphism of the male-specific portion of the Y chromosome has been
      increasingly used to describe the composition of the European gene pool and to
      reconstruct its formation. Here the theoretical grounds and the limitations of
      this approach are presented, together with the different views on debated issues.
      The emerging picture for the composition of the male gene pool of the continent
      is illustrated, but local peculiarities that represent departures from the main
      trends are also highlighted, in order to illustrate the main unifying feature,
      i.e. the overlay of recent patterns onto more ancient ones. A synopsis of the
      main findings and conclusions obtained in regional studies has also been
      compiled.

PMID- 17558588
TI  - Statures of 19th century Chinese males in America.
AB  - OBJECTIVE: This study considers statures of 19th century male Chinese immigrant
      to the American West and assesses how their personal characteristics were related
      with stature variation. SUBJECTS: The subjects were 1423 male Chinese prisoners
      received between 1850 and 1920 in the Arizona, California, Colorado, Idaho, New
      Mexico, Oregon, Utah and Washington state prisons. METHOD: The study compares
      19th century Chinese inmate statures with other studies and employs stature
      regression models on time, socio-economic status and residence within the USA to
      account for biological variation. RESULTS: Between 1830 and 1870, Chinese youth
      male stature declined by over 2 cm. Between 1820 and 1860, Chinese adult male
      stature also declined by over 2 cm. Chinese stature did not vary with socio
      economic status or residence. CONCLUSIONS: Nineteenth century Chinese emigrant
      statures were influenced more by political and economic events than socio
      economic status, and male emigrants' biological conditions may have deteriorated
      throughout the 19th century.

PMID- 17558589
TI  - The prediction of body fatness by BMI and skinfold thicknesses among children and
      adolescents.
AB  - BACKGROUND: Although the body mass index (BMI, kg m(-2)) is widely used as a
      measure of adiposity, it is a measure of excess weight, rather than excess body
      fat. It has been suggested that skinfold thicknesses be measured among overweight
      children to confirm the presence of excess adiposity. OBJECTIVE: The present
      study examined the additional information provided by skinfold thicknesses on
      body fatness, beyond that conveyed by BMI-for-age, among healthy 5- to 18-years
      old (n = 1196). METHODS AND PROCEDURES: Total body dual-energy X-ray
      absorptiometry (DXA) provided estimates of % body fat, and the sum of two
      skinfolds (triceps and subscapular) was used as an indicator of the overall
      skinfold thickness. RESULTS: As assessed by the multiple R(2)s and the residuals
      of various regression models, information on the skinfold sum significantly ( p <
      0.001) improved the prediction of body fatness beyond that obtained with BMI-for
      age. For example, the use of the skinfold sum, in addition to BMI-for-age,
      increased the multiple R(2)s for predicting % body fat from 0.81 to 0.90 (boys),
      and from 0.82 to 0.89 (girls). The use of the skinfold sum also reduced the
      overall prediction errors (absolute value of the residuals) for % body fat by 20
      30%, but these reductions varied substantially by BMI-for-age. Among overweight
      children, defined by a BMI-for-age >/=95th percentile, the skinfold sum reduced
      the predication errors for % body fat by only 7-9%. CONCLUSIONS: Although
      skinfold thicknesses, when used in addition to BMI-for-age, can substantially
      improve the estimation of body fatness, the improvement among overweight children
      is small.

PMID- 17558590
TI  - Spirometric values in Tunisian children: relationship with pubertal status.
AB  - BACKGROUND: Little is known about the effect of pubertal stages on lung function
      parameters in Tunisian children. AIM: The purpose of this study is to determine
      the relationship between lung function and pubertal stage in Tunisian children
      using anthropometric parameters. SUBJECTS AND METHODS: Pulmonary function
      parameters were measured with a Minato portable spirometer in 684 healthy
      Tunisian children (351 males and 333 females) aged between 8 and 16. The pubertal
      status was assessed for males and females according to the Tanner Method.
      RESULTS: A large variation was observed in the distribution of children's age and
      height by pubertal stages in both sexes. Height increased with age and pubertal
      stage in both males and females. The results also showed a significant increase
      in parameters of lung function (FVC, FEV(1), PEF, MEF(50) and MMEF(25-75)) with
      pubertal stage in Tunisian children. The analysis of covariance adjusting for
      anthropometric parameters showed that pubertal status had a significant
      independent effect on some pulmonary function parameters in both sexes.
      CONCLUSION: The results indicated that the parameters of pulmonary function for
      healthy Tunisian school children increased with age, height and pubertal stage.
      The present study has indicated that the use of only one morphological parameter
      such as height is not sufficient, but the pubertal status could be taken into
      account to standardize the lung function.

PMID- 17558591
TI  - The mysterious trend in American heights in the 20th century.
AB  - BACKGROUND: The secular trend in the height of the US population has been almost
      neglected in a comparative perspective, despite its being a useful indicator of
      early-life biological conditions. AIM: The study estimated the height of the US
      population and compared it to Western European trends after World War II.
      SUBJECTS AND METHOD: The complete set of NHES and NHANES data were analyzed,
      collected between 1959 and 2004 by the National Center for Health Statistics, in
      order to construct trends of the physical stature of US-born men and women
      limited to non-Hispanic blacks and whites. Also analyzed was the trend in the
      height of US military personnel whose parents were also born in the USA. The
      trends and levels were compared with those of several European populations.
      RESULTS: The increase in the physical stature of US adults slowed down by mid
      century concurrent with a substantial acceleration in height attainment in
      Western and Northern Europe. Military data corroborate this finding in the main.
      After being the tallest population in the world ever since colonial times,
      Americans are now shorter than most Western and Northern Europeans and as much as
      4.7-5.7 cm shorter than the Dutch, who are the tallest in world today.
      CONCLUSION: Given the well-established relationship between adult stature and
      early-life biological welfare, it was hypothesized that either American diets are
      sub-optimal or that the universal health care systems and social safety net of
      the European welfare states are providing a more favorable early-life health
      environment than does the American health care system.

PMID- 17558592
TI  - Gene-environment interaction in skeletal maturity and body dimensions of urban
      Oaxaca Mestizo schoolchildren.
AB  - OBJECTIVE: The study analyzed the relationship between skeletal age (SA) and the
      difference between skeletal and chronological ages (SA-CA) and body size among
      growth-stunted and well-nourished children. METHODS AND MATERIALS: Tanner
      Whitehouse 2 (TW2) 20 bone, radius-ulna-short (RUS) bone, and carpal SAs were
      analyzed in three cross-sectional samples of school children aged 6-13 years:
      Mestizo children (n = 396) from the city of Oaxaca, southern Mexico, and American
      Black (n = 570) and White (n = 432) from Philadelphia. The Oaxaca children were
      mild-to-moderately undernourished while the Philadelphia children were well
      nourished. The total sample included 1398 radiographs assessed with the Tanner
      Whitehouse protocol by a single, experienced rater. Maturity scores were
      converted to TW2 20 bone, RUS and carpal SAs. RESULTS: Correlations of SA and SA
      CA differences with body dimensions (height, sitting height, leg length, weight,
      triceps skinfold, arm and estimated midarm muscle circumferences) were consistent
      and approximately equal in magnitude for the well-nourished samples but were
      different among Oaxaca children. SAs of Philadelphia children were significantly
      more highly correlated with body dimensions than were SA-CA differences compared
      to Oaxaca Mestizo children. Patterns of RUS and carpal SA correlations with body
      size (height, sitting height, and leg length) in Oaxaca children were different
      from the Philadelphia samples. Oaxaca children tended to have advanced RUS SA and
      delayed carpal SA. CONCLUSION: Long bone complexes mature earlier than round bone
      complexes in Oaxaca children compared to Philadelphia Black and White children,
      resulting in short stature in Oaxaca children. Results suggest a gene-environment
      interaction effect on the program for skeletal growth and maturation in
      undernourished Oaxaca children compared to well-nourished Black and White
      children from Philadelphia.

PMID- 17558593
TI  - Heritability variations of morphometric traits in West Bengal (India) children
      aged 4-19 years: a mixed-longitudinal growth study.
AB  - BACKGROUND: Longitudinal and semi-longitudinal growth studies on siblings
      reflecting heritability changes during growth are very scarce. Moreover, studies
      of variables other than height, weight and BMI are virtually non-existent. AIM:
      The study compared changes in the heritability of six body lengths, four body
      breadths, and three indices between ages 4 and 19 years on the basis of a mixed
      longitudinal sample of siblings, and examined whether heritability estimates
      change during the growth period. The data consisted of 238 brothers and 214
      sisters from 134 middle-class nuclear families living in Kolkata (India). The
      analysis of sibling correlation was performed by maximum likelihood. The age
      related patterns of heritabilities of the various traits were described by a
      cubic spline. RESULTS: The heritability was very high and significant in most
      traits, and at all considered ages. Mean heritability in the 10 morphometric
      traits was 69.3%, which was higher than the heritability values for the three
      indices. CONCLUSIONS: These results confirmed the existence of age-related trends
      in heritability of the considered morphometric traits. The sharp decline of the
      heritabilities at adolescence in most of the morphometric traits, and the acromio
      iliac index in particular, may be due to the large inter-individual variation in
      the age at which the adolescent growth spurt is reached in both sexes.

PMID- 17558594
TI  - Somatotype and blood pressure of rural South African children aged 6-13 years:
      Ellisras longitudinal growth and health study.
AB  - BACKGROUND: Physique has been useful in assessing the outcome of underlying
      growth and maturity processes, which leads to a better understanding of variation
      in child and adult health. However, a high endomorphy rating has been associated
      with hypertension in adults, posing a serious threat to their health status,
      while receiving little attention in children. AIM: The study examined the
      association between somatotypes, body mass index (BMI) and blood pressure (BP) in
      6-13-year-old rural children, in Ellisras, South Africa. SUBJECTS: A total of
      1902 subjects (980 boys and 922 girls) aged 6-13 years were studied as part of
      the Ellisras Longitudinal Study. Height, weight, four skinfold sites, two
      breadths, and two girths were measured according to the International Society for
      the Advancement of Kinanthropometry (ISAK). The Heath-Carter method of
      somatotyping was used, together with internationally recommended cut-off points
      for BMI in children. Hypertension, defined as the average of three separate BP
      readings, where the systolic or diastolic BP is greater than or equal to the 95th
      percentile for age and sex, was determined. RESULTS: The prevalence of
      hypertension ranges from 1 to 5.8% in boys and 3.4-11.4% in girls. The prevalence
      of overweight ranges from 1.1 to 2.9% in boys and 0.6-4.6% in girls. Systolic BP
      and BMI showed a significant positive correlation at age 6 years (r = 0.436) and
      10-13 years (r = 0.180-0.246 in boys and r = 0.221-0.271 in girls). Diastolic BP
      showed an insignificant correlation with the BMI and somatotype components in
      boys and girls. CONCLUSION: A significant association exists between BP and BMI,
      and ectomorphy components even after being adjusted for age, gender and height.
      The need to manage hypertensive individuals is evident in this sample to combat
      this chronic disease from an early age. Follow-up studies should investigate the
      relationship between BP and the dietary intake of these children.

PMID- 17558595
TI  - What evidence is there that adjustment for adult height influences the
      relationship between birth weight and blood pressure?
AB  - BACKGROUND: The inverse association between birth weight and blood pressure may
      partly be the result of inappropriate adjustment for adult body size, but it
      remains unclear whether adjustment for adult height elicits this effect. AIM: The
      study investigated the impact of adjustment for adult height on the relationship
      between birth weight and blood pressure. METHODS: A systematic search of Medline
      from 1996 to 2006 was conducted using the terms 'birth weight', 'blood pressure'
      and 'hypertension', and any papers containing linear regression analyses of blood
      pressure on birth weight for populations with an average age of 25+ were eligible
      for inclusion in comparative meta-analyses. RESULTS: None of the 30 studies
      identified had published regression coefficients for blood pressure on birth
      weight before and after adjustment for adult height, and only two studies were
      found to adjust for adult height at all. Data from these studies were obtained,
      and it was found that adjustment for height made the association between birth
      weight and systolic blood pressure (SBP) more negative in one study but less
      negative in the other. When compared with meta-analyses of comparable models, it
      was found that both studies were substantially different from the combined
      estimate of the relationship between birth weight and SBP. CONCLUSIONS: Both the
      differences between the two selected studies and their differences from the
      combined estimates obtained by meta-analysis are likely to be due to differences
      in the age of the participants. The relationship between birth weight and SBP
      tended to become more strongly inverse in studies with older participants.
      Additionally, the correlations between height and SBP were found to change from
      positive to negative with increasing age, which explained the differential impact
      of adjustment for height in the two selected studies. It therefore appears that
      adjustment for height may have little effect for older participants, but more so
      for younger participants.

PMID- 17558596
TI  - TW3 and Fels skeletal ages in elite youth soccer players.
AB  - BACKGROUND: Skeletal age (SA) tends to be advanced for chronological age (CA) in
      adolescent male soccer players. AIM: The study compared SA assessments with the
      TW3 and Fels methods in a sample of male, elite youth soccer players. METHODS:
      SAs were assessed with the Tanner-Whitehouse 3 (TW3) radius-ulna-short bone (RUS)
      and Fels methods in a sample of 40 elite youth soccer players 12.5-16.1 years of
      age. Players were classified as late, on time or early on the basis of relative
      SA, the difference between SA and CA. Players who reached skeletal maturity were
      labeled mature. RESULTS: SA was in advance of CA. Among 14 players >15.0 years,
      two are skeletally mature with the Fels method (CA 15.7 and 15.9 years), while 11
      are skeletally mature with the TW3 method (CA 15.0-16.1 years). CONCLUSION: The
      TW3 and Fels methods yield different SAs in elite youth soccer players.
      Significantly more 15-year-old boys are classified as skeletally mature with the
      TW3 method than with the Fels method. These observations have implications for
      international age group competitions as well as for medico-legal circumstances
      that require CA verification. SA is not a valid measure of CA and should not be
      used as such.

PMID- 17558597
TI  - The effects of medications on circulating levels of cardiac natriuretic peptides.
AB  - Circulating cardiac natriuretic peptide levels are being used increasingly in a
      range of clinical circumstances. Since it is evident that drugs used in the
      treatment of cardiovascular disorders can modulate natriuretic peptide levels, we
      here review the literature documenting these effects. Diuretics, blockers of the
      renin-angiotensin system, vasodilator agents, dopamine-like agonists, amiodarone,
      and perhaps allopurinol and statins suppress natriuretic peptide levels, most
      obviously in heart failure. Beta-blockers stimulate natriuretic peptide
      concentrations in hypertensive subjects, whereas in heart failure they have
      little effect or are stimulatory in the short term and inhibitory with sustained
      therapy. Digitalis compounds and aspirin tend to increase natriuretic peptide
      levels, and calcium channel blocking agents have varying effects depending on the
      individual drug and duration of administration. The effects of other drugs are
      less clear. Additional information is needed regarding the effects of medications
      along with dissection of the role of altered cardiac secretion versus changes in
      plasma clearance as explanation for drug-induced perturbations in natriuretic
      peptide concentrations. In the meantime, clinicians need to consider the known
      effects of medications when interpreting plasma levels of the cardiac natriuretic
      peptides.

PMID- 17558599
TI  - Ischemia-reperfusion and cardioprotection: a delicate balance between reactive
      oxygen species generation and redox homeostasis.
AB  - Ischemia-reperfusion injury of the myocardium has long been a subject of intense
      research. Cardiac preconditioning, an associated phenomenon, has also been
      critically investigated over the past two decades. Although the biochemistry of
      ischemia-reperfusion and its association with oxidative metabolism has long been
      established, recent studies have further revealed a more intricate role of a
      number of reactive oxygen-nitrogen species in those processes. Emerging evidence
      suggests that an elaborate network of enzymes (and other biomolecules) dedicated
      to the generation, utilization, and diminution of reactive oxygen-nitrogen
      species maintains the redox homeostasis in the myocardium, and any perturbation
      of its status has distinctive effects. It thus appears that while excessive
      generation of reactive species leads to cellular injury, their regulated
      generation may cause transient and reversible modifications of cellular proteins
      leading the transmission of intracellular signals with specific effects. Taken
      together, generation of reactive oxygen-nitrogen species in the myocardium plays
      a nodal role in mediating both ischemic injury and cardioprotection.

PMID- 17558600
TI  - Multislice cardiac computed tomography in symptomatic middle-aged women.
AB  - OBJECTIVE: To assess the accuracy of multislice cardiac computed tomography
      (MSCT) for detection of significant coronary artery disease (CAD) in middle-aged
      symptomatic women. METHODS: We included 70 women (51+/-8 years) with complaints
      of chest pain or dyspnea, and an abnormal maximum exercise electrocardiogram
      (ECG) (8.6+/-1.4 metabolic equivalents). All had a MSCT using a 16 detector rows
      scanner, and coronary arteriography (CA). Blinded results of the two modalities
      were compared using a segment, vessel, and patient-based analysis. RESULTS: On
      MSCT 36% had normal coronaries, 24% had significant CAD requiring
      revascularization, and the remainder had mild CAD. MSCT had reasonably high
      diagnostic accuracy at segment level (negative predictive value of 95%, positive
      predictive value 81%, specificity 99%, and sensitivity 50%), regarding single or
      multivessel CAD when both nonassessable and assessable segments were included in
      the analysis. The agreement between the segments comparing MSCT and CA for
      significant CAD was excellent at 98% (kappa value 0.89). CONCLUSIONS: In this
      cohort of middle-aged symptomatic women with an abnormal stress test, 24% had
      significant CAD requiring intervention. MSCT was highly accurate in diagnosing
      significant CAD with an excellent negative predictive value.

PMID- 17558598
TI  - Molecular genetics of congenital diaphragmatic defects.
AB  - Congenital diaphragmatic hernia (CDH) is a severe birth defect that is
      accompanied by malformations of the lung, heart, testis, and other organs.
      Patients with CDH may have any combination of these extradiaphragmatic defects,
      suggesting that CDH is often a manifestation of a global embryopathy. This review
      highlights recent advances in human and mouse genetics that have led to the
      identification of genes involved in CDH. These include genes for transcription
      factors, molecules involved in cell migration, and extracellular matrix
      components. The expression patterns of these genes in the developing embryo
      suggest that mesenchymal cell function is compromised in the diaphragm and other
      affected organs in patients with CDH. We discuss potential mechanisms underlying
      the seemingly random combination of diaphragmatic, pulmonary, cardiovascular, and
      gonadal defects in these patients.

PMID- 17558601
TI  - Systemic and intracardiac vascular endothelial growth factor and angiopoietin-1
      and -2 levels in coronary artery disease: effects of angioplasty.
AB  - BACKGROUND: Vascular growth factors are involved in the pathophysiology of human
      atherosclerotic vascular disease and plaque destabilization. We hypothesized that
      in stable patients with coronary artery disease (CAD), plasma levels of vascular
      endothelial growth factor (VEGF) and angiopoietins 1 and 2 (as indices of
      angiogenesis) would be no higher in coronary sinus blood when compared to the
      aortic root, coronary ostium, and peripheral femoral vein. Secondly, we
      hypothesized that percutaneous coronary intervention (PCI; angioplasty+/
      stenting) would increase intracardiac levels of these indices, perhaps by
      destabilizing coronary plaques. METHODS: Patients undergoing elective diagnostic
      coronary angiography (n = 70; mean age 58.8+/-11.2 years) of which 37 proceeded
      to PCI were recruited. Blood samples were obtained from the aortic root, coronary
      ostium, coronary sinus, and femoral vein. Plasma VEGF, angiopoietin-1 and
      angiopoietin-2 levels were measured by immunoassays. RESULTS: There were no
      significant differences in VEGF, angiopoietin-1 and angiopoietin-2 levels when
      aortic root, coronary ostium, coronary sinus, and femoral vein samples were
      compared (P = not significant (NS)). In patients undergoing PCI, peripheral
      angiopoietin-2 levels were increased significantly post PCI (P = 0.01). There was
      also a difference in intracardiac gradient (that is, aortic root-coronary sinus
      difference) in angiopoietin-1 (P = 0.02) following PCI. No significant changes in
      VEGF with PCI were noted. CONCLUSION: There were no differences in indices of
      angiogenesis when aortic root, coronary ostium, coronary sinus, and femoral vein
      levels of VEGF and angiopoietins are compared, suggesting that peripheral blood
      measurements of these indices are comparable to intracardiac levels. Although no
      immediate effects were observed in soluble VEGF levels, PCI affected intracardiac
      angiopoietin-1 with a systemic release of angiopoietin-2. Further investigations
      are necessary to determine the relative systemic and intracardiac effects of the
      angiopoietins in vascular remodelling post PCI.

PMID- 17558603
TI  - Characterization of familial and sporadic arrhythmogenic right ventricular
      cardiomyopathy in Finland.
AB  - BACKGROUND: Autosomal dominant inheritance is reported in arrhythmogenic right
      ventricular cardiomyopathy (ARVC) but the prevalence of the familial and sporadic
      forms in the general population is unknown. AIM: To evaluate the familial
      occurrence and clinical features of ARVC in the genetically homogenous Finnish
      population. METHODS: The study included 29 Finnish ARVC index patients and 135
      relatives from 21 families evaluated. They underwent echocardiography, 24-hour
      electrocardiographic monitoring, signal-averaged electrocardiography, and
      exercise stress test. RESULTS: Twenty-two index patients had ventricular
      arrhythmias as first manifestation, and three developed arrhythmias later. The
      right ventricle (RV) was mildly affected in 22 and strongly dilated in 7 index
      patients. Patients with dilated RV manifested first symptoms at younger age (mean
      28 years) than those without RV dilatation (mean 38 years). Of the 135 relatives,
      ARVC was present in 12 (9%) patients belonging to 5 of the 21 families studied,
      resulting in 24% familial involvement. In addition, 46 relatives (34%) had subtle
      cardiac abnormalities, suggesting subclinical presentation. CONCLUSIONS: The ARVC
      in Finland presents with distinct arrhythmic and RV dilative subtypes. The
      sporadic disease is similar to the familial one which may reflect low penetration
      in relatives. The proportion of familial manifestation of ARVC in Finland seems
      comparable to that elsewhere in Europe.

PMID- 17558602
TI  - Apolipoprotein A-I breakdown is induced by thrombolysis in coronary patients.
AB  - BACKGROUND: The outcome of percutaneous coronary intervention (PCI) is apparently
      worse in patients receiving a prior thrombolytic therapy ('facilitated PCI').
      Recombinant tissue-type plasminogen activator (rt-PA) can degrade circulating
      high-density lipoproteins (HDL) bound apolipoprotein A-I (apoA-I), thus possibly
      reducing the vascular protective activity. There have never been reports of the
      detection of apolipoprotein breakdown products in the circulation. AIM: We
      studied the potential interactions between the protein components of HDL and
      tenecteplase, infused as thrombolytic therapy. METHODS: Sera from a total of 40
      patients with acute myocardial infarction (AMI), unstable angina (UA), and
      dilative cardiomyopathy (controls) were investigated. AMI patients underwent
      either immediate PCI or were treated with tenecteplase thrombolysis. RESULTS:
      Products of extensive proteolysis of apoA-I were found in many acute coronary
      patients treated with tenecteplase, and in some AMI patients before starting the
      treatment (time 0). These were not detected in controls, UA patients as well as
      AMI patients undergoing immediate PCI. Small pre-beta-HDLs were selectively
      degraded. CONCLUSION: Significant apoA-I degradation occurs in AMI patients after
      thrombolytic treatment. This finding may provide a potential mechanism for the
      apparent reduction of benefit of facilitated versus nonfacilitated PCI.

PMID- 17558604
TI  - Ferritin and ferritin isoforms II: protection against uncontrolled cellular
      proliferation, oxidative damage and inflammatory processes.
AB  - Ferritin is a major iron storage protein involved in the regulation of iron
      availability. Each ferritin molecule comprises 24 subunits. Various combinations
      of H-subunits and L-subunits make up the 24-subunit protein structure and these
      ferritin isoforms differ in their H-subunit to L-subunit ratio, as well as in
      their metabolic properties. Ferritin is an acute-phase protein and its expression
      is up-regulated in conditions such as uncontrolled cellular proliferation, in any
      condition marked by excessive production of toxic oxygen radicals, and by
      infectious and inflammatory processes. Under such conditions ferritin up
      regulation is predominantly stimulated by increased reactive oxygen radical
      production and by cytokines. The major function of ferritin in these conditions
      is to reduce the bio-availability of iron in order to stem uncontrolled cellular
      proliferation and excessive production of reactive oxygen radicals. Ferritin is
      not, however, indiscriminately up-regulated in these conditions as a marked shift
      towards a predominance in H-subunit rich ferritins occurs. Preliminary
      indications are that, while the L-subunit primarily fulfils the conventional iron
      storage role, the H-subunit functions primarily as rapid regulator of iron
      availability, and perhaps indirectly as regulator of other cellular processes. It
      is suggested that the optimum differential expression of the two subunits differ
      for different cells and under different conditions and that the expression of
      appropriate isoferritins offers protection against uncontrolled cellular
      proliferation, oxidative stress and against side effects of infectious and
      inflammatory conditions.

PMID- 17558605
TI  - Mechanisms responsible for enhanced fatty acid utilization by perfused hearts
      from type 2 diabetic db/db mice.
AB  - The aim of this study was to determine the biochemical mechanism(s) responsible
      for enhanced FA utilization (oxidation and esterification) by perfused hearts
      from type 2 diabetic db/db mice. The plasma membrane content of fatty acid
      transporters FAT/CD36 and FABPpm was elevated in db/db hearts. Mitochondrial
      mechanisms that could contribute to elevated rates of FA oxidation were also
      examined. Carnitine palmitoyl transferase-1 activity was unchanged in
      mitochondria from db/db hearts, and sensitivity to inhibition by malonyl-CoA was
      unchanged. Malonyl-CoA content was elevated and AMP kinase activity was decreased
      in db/db hearts, opposite to what would be expected in hearts exhibiting elevated
      rates of FA oxidation. Uncoupling protein-3 expression was unchanged in
      mitochondria from db/db hearts. Therefore, enhanced FA utilization in db/db
      hearts is most likely due to increased FA uptake caused by increased plasma
      membrane content of FA transporters; the mitochondrial mechanisms examined do not
      contribute to elevated FA oxidation observed in db/db hearts.

PMID- 17558606
TI  - Myocardial insulin action and the contribution of insulin resistance to the
      pathogenesis of diabetic cardiomyopathy.
AB  - Heart disease is the leading cause of death in patients with insulin resistance
      and type 2 diabetes (DM2). Even in the absence of coronary artery disease and
      hypertension, functional and structural abnormalities exist in patients with well
      controlled and uncomplicated DM2. These derangements are collectively designated
      by the term diabetic cardiomyopathy (DCM). Changes in myocardial energy
      metabolism, due to altered substrate supply and utilization, largely underlie the
      development of DCM. Insulin is an important regulator of myocardial substrate
      metabolism, but also exerts regulatory effects on intracellular Ca2+ handling and
      cell survival. The current paper reviews the multiple functional and molecular
      effects of insulin on the heart, all of which ultimately seem to be
      cardioprotective both under normal conditions and under ischemia. In particular,
      the dismal consequences of myocardial insulin resistance contributing to the
      development of DCM will be discussed.

PMID- 17558607
TI  - Aldehydes and disturbance of carbohydrate metabolism: some consequences and
      possible approaches to its normalization.
AB  - There are many well-documented errors of metabolism involving genetic defects
      that affect carbohydrate utilization. The array of disorders includes the
      defective utilization of glucose, as well as enzymatic deficiencies in glycolysis
      and gluconeogenesis, and the pentose phosphate pathway. Besides, there is
      considerable literature about metabolic syndrome and diabetes. However, the main
      problem of their origin remains obscure. Also, it is presently beyond doubt that
      there are various causes of insulin resistance. The development of insulin
      resistance may be associated not only with insulin production disorders or
      presence of insulin antagonists but also with modification of the number of
      receptors and sensitivity of peripheral tissues. The insulin resistance
      originates from insulin signal transmission defects at its initial stages. It is
      presently uncertain which mechanisms of adaptation regulation are activated or
      should be activated under hyperglycemia conditions. This is the main problem of
      the selection of strategy of hyperglycemia treatment but it is important that
      aldehydes - the secondary products of lipid peroxidation and protein glycation
      (malondialdehyde and methylglyoxal) - make a contribution to abnormal metabolism.
      As far as the role of methylglyoxal in inhibition of antioxidant enzymes is
      concerned, the involvement of the ketoaldehyde in such processes as oxidative
      stress, cell proliferation control, and carbohydrate metabolism disorders does
      not cast any doubt.

PMID- 17558608
TI  - Noradrenergic function in suicide.
AB  - Although abnormalities in serotonergic function have been the major focus of
      studies on suicidal behavior, several studies indicate that abnormalities of
      noradrenergic function may also be involved in the pathophysiology of suicide. In
      this paper, we have reviewed some of the noradrenergic studies in suicide,
      including studies of the biosynthetic enzyme for norepinephrine, tyrosine
      hydroxylase (TH), the receptors for norepinephrine, alpha- and beta-adrenergic
      receptors, as well as the signaling cascades linked to beta-adrenergic receptors.
      In general, these studies indicate that the protein expression of TH, as well as
      alpha2- and beta2-adrenergic receptors, is increased in the postmortem brain of
      suicide victims. More studies are needed in order to examine extensively the role
      of noradrenergic function in suicidal behavior.

PMID- 17558609
TI  - Suicide in Ethiopian immigrants in Israel: a case for study of the genetic
      environmental relation in suicide.
AB  - Immigration is a major life stress event, which has been associated with
      increased levels of mental health problems. The linkage between immigration and
      suicide has been studied in various societies, with conflicting results.
      Extremely high rates of suicide have been found repeatedly among the population
      of the Ethiopian immigrants in Israel. These rates were significantly higher than
      other immigrant populations in the country. Possible explanations for this
      disparity are discussed, and future directions for further study of this area are
      suggested.

PMID- 17558610
TI  - Violent and nonviolent methods of suicide: different patterns may be found in men
      and women with severe depression.
AB  - The objective of this study was to investigate violent and nonviolent suicidal
      acts in men and women with severe depression. The records of 98 suicide victims,
      who had been admitted to the Department of Psychiatry, Lund University Hospital,
      Sweden between 1956 and 1969, were evaluated and the subjects were monitored up
      to 1998. The female group displayed a significant linear trend for nonviolent
      completed suicide after one suicide attempt, and even more significantly, after
      repeated attempts. A switch from only nonviolent suicide attempts to completed
      violent suicide was significantly more common in men than in women. These
      different progressions may contribute to the expected finding that men used
      violent methods for completed suicide more often than women.

PMID- 17558611
TI  - Low resilience in suicide attempters.
AB  - Resilience is an important personality feature that is thought to be protective
      against the development of psychiatric disorder. However, it appears not to have
      been previously examined directly in relation to suicidal behavior. Therefore,
      with the recent development of a resilience scale, the purpose of this
      preliminary study was to examine resilience in relation to attempting suicide. In
      order to do this 100 abstinent substance dependent patients were interviewed
      about whether or not they had ever attempted suicide and completed the Connor
      Davidson Resilience Scale. The results showed that patients who had attempted
      suicide (N=41) had significantly lower resilience scale scores than patients who
      had never attempted suicide (N=59). This suggests the possibility that low
      resilience may be a risk factor for suicidal behavior. Longitudinal studies among
      suicide attempters, including measures of depression, may further evaluate the
      possible relevance of resilience to suicidal behavior.

PMID- 17558612
TI  - Beliefs about gender differences in methods and causes of suicide.
AB  - Forty undergraduate students (20 males, 20 females) made judgments about the
      relationship between an individual's gender and the method of suicide most likely
      to be chosen by that individual. The perceived relationship between different
      precipitating events for suicide and the method of suicide were also examined, as
      were the participants' judgments about the moral justification of suicide in
      response to different traumatic situations. The results indicated clear and
      consistent beliefs about the relationship between the gender of the potential
      suicide victim, the method of suicide likely to be chosen, and whether or not the
      cause of the suicide was judged harshly or sympathetically. Understanding how the
      gender of an at-risk individual interacts with an observer's beliefs and moral
      perspective should help us predict when suicide threats will be taken seriously
      and what form of intervention will take place.

PMID- 17558613
TI  - Determination of suicide in South Africa: medical practitioner perspectives.
AB  - Decisional processes underlying the determination of a suicide in the largest
      injury surveillance system currently available in South Africa are assessed
      through face-to-face semi-structured interviews with 32 medical practitioners
      involved in the system. Focus is placed on their current work circumstances and
      practices, and views of operational and empirical criteria proposed by US
      experts. Common themes and discrepancies in opinions emerged regarding the
      quality of the data currently available for suicide determinations, and regarding
      the importance and difficulty in assessing the US-developed criteria in South
      Africa. A truly standard approach is unlikely without considerable changes to the
      medico-legal system.

PMID- 17558614
TI  - Psychiatric aftercare and suicide risk: a case-control study using blind rating.
AB  - Blindly abstracted records of last episode of care together with aftercare
      records of 39 psychiatric patient suicides and their matched controls were rated
      blind for suicidal talk during aftercare, reduction of aftercare at last
      appointment and high-low suicide risk. Neither suicidal talk nor reduction of
      aftercare was confirmed as a predictor of suicide, although trends in the
      predicted directions were observed. Blind estimates of high-low risk correctly
      identified a significant minority (40%) of suicides but at the cost of
      misclassifying 60% as controls. Evidence is still lacking that clinicians blind
      to case identity may, from records, reliably distinguish a majority of suicides
      from their matched controls. Some implications for practice and research are
      discussed.

PMID- 17558615
TI  - Identification of suicide risk factors in Medellin, Colombia: a case-control
      study of psychological autopsy in a developing country.
AB  - The incidence, methods and risk factors for suicide may vary among the different
      cultures, which makes necessary to study the risk factors for suicide in specific
      settings in order to design adequate intervention strategies. This study aims to
      determine the risk factors for suicide in Medellin (Colombia). It is a case
      control study conducted among 108 individuals who committed suicide and 108
      deceased in accidents, matched for age and gender. Both cases and controls were
      examined by means of psychological autopsy. Conditional logistic regression
      analysis identified the following factors: Adverse life events in the last six
      months (OR=11.81, 95% CI: 4.29-32.52), family history of suicide (OR=10.82, 95%
      CI: 2.23-52.47), major depressive episode (OR=4.58, 95% CI: 1.53-13.67) and
      expression of a wish to die (OR=3.54, 95% CI: 1.25-10.06). These findings may
      suggest that risk factors for suicide are similar across cultures.

PMID- 17558616
TI  - The psychometric properties and correlates of the Reynolds' suicide ideation
      questionnaire with Kuwaiti and American students.
AB  - In samples of Kuwaiti (n=460) and American (n=273) college students, the Reynolds
      Suicide Ideation Questionnaire (SIQ) proved to have good internal consistency and
      concurrent validity with measures of anxiety, optimism, pessimism, death
      obsession, obsession-compulsion, and ego-grasping. The SIQ was factorially
      complex in both samples, but the eight critical items showed a similar two-factor
      pattern in both samples. It is important to note that in spite of the great
      differences between Kuwait and US students and their cultures, the findings were
      quite similar. By and large, the psychological correlates of the SIQ may have
      cross-cultural generality.

PMID- 17558617
TI  - The evolving neurobiology of depression: from synapses to neurons, circuits and
      loops.

PMID- 17558618
TI  - Synaptic P2X7 receptor regenerative-loop hypothesis for depression.
AB  - Forty-five years ago the surprising discovery was made, in a Melbourne University
      laboratory, that peripheral synapses exist that release neither noradrenaline nor
      acetylcholine. The same laboratory went on to show that one of these then novel
      transmitters is adenosine 5'-triphosphate (ATP), for which a class of receptors
      has been dubbed P2X7. Recent linkage studies have shown that the P2X7 gene is
      associated with major depression and bipolar disorder. This speculative paper
      considers possible mechanisms that could link polymorphisms in the P2X7 gene with
      the functioning of neural networks, especially in the hippocampus. A selective
      review of the neurobiological literature on the location and function of the P2X7
      receptor at synapses and on astrocytes as well as microglial cells was performed
      in the context of determining viable hypotheses as to the function of these
      receptors during synaptic transmission in the neural networks of the hippocampus.
      It is suggested that P2X7 receptors participate in a regenerative loop at central
      glutamatergic synapses. In this loop glutamate-evoked release of ATP from both
      astrocytes and microglia cells, as well as ATP derived from an autocatalytic
      release from astrocytes, provides purines that can act on presynaptic P2X7
      purinergic receptors. This increases glutamate release to further the amount of
      ATP at the synapse, leading to a new functional state of the neural network in
      which the synapse participates. This synaptic ATP can also act on microglia P2X7
      receptors to release the cytokine tumour necrosis factor-alpha (TNF-alpha), as
      can glutamate, with this TNF-alpha acting on the post-synaptic neuronal membrane
      to increase glutamate alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA)
      receptors there. As synaptic ATP and glutamate are maintained by the regenerative
      loop they provide a sustained release of TNF-alpha, and therefore of AMPA
      receptor enhancement, increasing synaptic efficacy, and so contributing to the
      new functional state of the neural network. Infections can change this state by
      activating toll-like (TOL) receptors on the microglia concomitantly with their
      P2X7 receptor activation by the regenerative loop, thereby releasing the cytokine
      interleukin-1beta, which decreases the AMPA receptors in the neural membrane, so
      decreasing synaptic efficacy and changing the functional state of the neural
      network in which the synapse resides. Polymorphisms in the P2X7 gene that modify
      operation of the regenerative loop or the release of cytokines, as can
      infections, change the functional state of neural networks, which may then lead
      to vulnerability to mood disorders.

PMID- 17558619
TI  - Tobacco smoking within psychiatric inpatient settings: biopsychosocial
      perspective.
AB  - Tobacco smoking remains a neglected issue within general psychiatry despite high
      rates of associated morbidity and mortality. While there has been a coordinated
      community campaign to reduce tobacco smoking within the general population,
      mental health facilities have been reluctant to adopt such regulatory controls,
      and rarely target smoking prevention or treatment. This paper summarizes and
      discusses evidence relating to the clinical impact of tobacco smoking within
      inpatient psychiatric settings. A selective review of psychiatric and
      psychological research on smoking within inpatient settings was conducted, with a
      particular focus on the influence of smoking on the physical and mental health,
      pharmacotherapy, and social interactions of patients during their inpatient stay.
      Patients frequently alter their smoking habits during inpatient treatment, which
      can affect both their presentation and pharmacotherapeutic management. Smoking
      also appears to play a central role in social interactions on the ward, with
      staff frequently using cigarettes to reinforce certain behaviours. Despite
      current guidelines, mental health professionals rarely address nicotine use among
      their patients. Nevertheless, programmes that assist patients to quit during an
      inpatient stay have been shown to be both efficacious and cost-effective.
      Strategies that address staff concerns and assist in the implementation of
      effective smoking bans on psychiatric units are also available. Cessation should
      be a key component of inpatient treatment planning because this setting provides
      a safe and timely opportunity to help patients quit. A flowchart of interventions
      that could be incorporated within standard inpatient settings is proposed.

PMID- 17558620
TI  - Age shall not weary them: mental health in the middle-aged and the elderly.
AB  - OBJECTIVE: The prevalence of mental disorders in the elderly is disputed. The
      debate in this area can be informed by data from large population surveys that
      contain sufficient elderly participants. The aim of the present paper was to
      provide the first direct comparison of the prevalence and demographic correlates
      of ICD-10 anxiety and affective disorders in the middle-aged and the elderly.
      METHOD: The 12 month prevalence and demographic correlates of affective and
      anxiety disorders were compared in a community sample of middle-aged and elderly
      Australian residents who took part in the Australian National Mental Health and
      Well-being Survey (NMHWS). RESULTS: One in seven middle-aged participants and one
      in 16 elderly participants experienced symptoms consistent with any anxiety or
      affective disorder in the preceding 12 months. Compared to the middle-aged
      participants, the elderly had lower rates for most affective and anxiety
      disorders, and for the combined presence of any disorder. Demographic correlates
      of mental disorder, especially marital status, were different for the two groups.
      CONCLUSIONS: Community-dwelling elderly in Australia have lower rates of mental
      disorder compared to the middle-aged. Differences in demographic correlates
      between groups support the notion that the determinants of mental disorder in the
      elderly differ substantially from those in middle age.

PMID- 17558621
TI  - Prediction of outcome for veterans with post-traumatic stress disorder using
      constructs from the transtheoretical model of behaviour change.
AB  - OBJECTIVE: Post-traumatic stress disorder (PTSD) is a disabling condition,
      sometimes unresponsive to treatment. The aim of the present study was to examine
      the predictive utility of constructs from the transtheoretical model of behaviour
      change (TTM) known to predict outcome for other disorders. METHOD: A sample of 50
      veterans presenting for a PTSD treatment programme provided data for this
      longitudinal study. Variables were assessed at four time-points during the
      treatment programme. Multiple regression and mixed-effects regression were
      utilized to determine the predictive utility of variables from the TTM. RESULTS:
      Allocated stage of change at the time of a 2 day introduction programme predicted
      follow-up symptom severity, but changes therein during treatment did not predict
      changes in symptom severity. However, changes in the continuous readiness-to
      change variable and behavioural processes of change were predictive of such
      changes. CONCLUSIONS: Despite some difficulties in the application of the TTM to
      PTSD, the model does appear to predict treatment outcome. Veterans who have
      increased readiness to change and who make more use of behavioural processes of
      change are likely to have improved outcomes.

PMID- 17558622
TI  - Borderline personality disorder, mother-infant interaction and parenting
      perceptions: preliminary findings.
AB  - OBJECTIVE: Parents diagnosed with borderline personality disorder (BPD) are
      likely to find the emotional aspects of parenting challenging. Research into the
      difficulties that these parents experience, however, is lacking. The aims of the
      present study were to (i) gain an understanding of the interactional patterns of
      mothers with BPD and their infants and (ii) to explore the parenting perceptions
      of mothers with BPD. METHOD: Two groups of mother-infant dyads were recruited:
      mothers with BPD and their infants; and community mothers and their infants.
      Groups were compared on mother-infant interaction patterns and on maternal self
      perceptions of parenting. RESULTS: Mothers with BPD were found to be less
      sensitive and demonstrated less structuring in their interaction with their
      infants, and their infants were found to be less attentive, less interested and
      less eager to interact with their mother. Furthermore, mothers with BPD reported
      being less satisfied, less competent and more distressed. CONCLUSIONS: Early
      intervention needs to be provided to mothers with BPD to promote maternal
      sensitivity and maternal perceptions of competence.

PMID- 17558623
TI  - Obesity and metabolic syndrome in a psychiatric rehabilitation service.
AB  - OBJECTIVE: People with schizophrenia and bipolar disorders suffer from increased
      rates of obesity and metabolic syndrome. Metabolic disorders add to the burden of
      disease and affect treatment and rehabilitation outcomes. This study aimed to
      study the prevalence of obesity and metabolic syndrome in people with chronic
      psychotic disorders in a psychiatric rehabilitation setting. METHOD: All patients
      in the psychiatry rehabilitation program were assessed for obesity and metabolic
      syndrome using the definition of International Diabetes Federation (2005) was
      conducted as part of clinical protocol recently introduced into practice.
      RESULTS: A total of 221 patients were assessed. The prevalence of obesity was 59%
      and metabolic syndrome 68%. Metabolic syndrome was more frequent in patients
      receiving polypharmacy with multiple antipsychotics and mood stabilisers. Rates
      of nontreatment for metabolic disorders ranged from 30% to 88%. CONCLUSIONS: The
      rates of obesity and metabolic syndrome in patients with chronic severe mental
      disorders on antipsychotic drug treatment were 2 to 3 times that in the general
      population. A majority of them were untreated. Detection, monitoring and
      appropriate treatment of obesity and metabolic disorders should be a component of
      an assertive care management program to reduce morbidity and mortality and
      improve rehabilitation outcomes.

PMID- 17558624
TI  - Longitudinal follow up of primary insomnia patients in a psychiatric clinic.
AB  - OBJECTIVE: Insomnia could be a symptom of underlying psychiatric or physical
      disorder, a risk factor for other psychiatric disorder, or a discrete psychiatric
      disorder per se. In order to determine the nosological status of primary
      insomnia, an outcome study was carried out to investigate its diagnostic
      stability and its relationship to subsequent psychiatric disorders. METHODS:
      Fifty-three primary insomnia patients in a university hospital psychiatric
      outpatient clinic were assessed by retrospective case note review, followed by a
      6 month prospective follow up with Structured Clinical Interview Schedule for DSM
      IV In-patient (SCID-I/P, version 2.0, and a sleep questionnaire. RESULTS: The
      majority of patients (n =44, 83%) did not develop other psychiatric disorders
      after 13.4+/-1.2 years from the onset of insomnia. Nine patients (17%) developed
      mood disorder (n =6), anxiety disorder (n =2) and somatoform disorder (n =1) at
      6.3+/-2.3 years after the onset of insomnia. Subjective deterioration of insomnia
      and a shorter duration of sleep symptoms at the first consultation were
      associated with the development of secondary psychiatric disorders. Approximately
      one-third (n =17, 32%) reported symptoms improvement and six (13.2%) were free
      from medications. Better education was the only factor that predicted improvement
      in symptoms. CONCLUSIONS: There existed a longitudinal diagnostic stability of
      primary insomnia in a majority of clinical patients. However, in a proportion of
      patients, it might either be a risk factor or a prodrome of mood or anxiety
      disorders.

PMID- 17558625
TI  - Impact of a workshop on motivation to pursue a career in child and adolescent
      mental health.
AB  - OBJECTIVE: The aim of the present study was to determine whether a 3 h workshop
      on child and adolescent mental health positively influenced nursing, occupational
      therapy and social work students' career intentions. METHOD: Students
      participating in the study were asked to complete a questionnaire before and
      after attending the workshop and again at follow up. Post-workshop students and
      their educators were also asked to complete a questionnaire on the perceived
      quality of teaching. Career intentions scores were analysed using generalized
      mixed linear models. The quality of teaching data was analysed using Kruskal
      Wallis and Mann-Whitney U-tests. RESULTS: The workshops were attended by 373
      students and had an immediate positive impact on students' career intentions in
      relation to child and adolescent mental health. A repeated measures analysis
      showed an overall time effect (F(2,546)=16.29, p <0.0001). A multiple comparison
      test of this difference showed a highly significant positive increase in career
      intentions between pre-workshop and post-workshop ratings (p <0.0001), and the
      magnitude of this difference dropped between post-workshop assessment and follow
      up (p =0.004). However, there was no significant change between pre-workshop and
      follow-up ratings (p =0.43). The study also highlighted that a number of students
      consistently rated working in child and adolescent mental health very favourably.
      CONCLUSIONS: The workshop did have a positive influence on students' career
      intentions, but this change was not enduring. However, a number of students did
      indicate an interest in working in the area; and enhancing this interest while
      addressing the lack of training in this area would be worthwhile.

PMID- 17558626
TI  - Idiopathic recurrent catatonia needs maintenance lorazepam: case report and
      review.
AB  - OBJECTIVES: Catatonia as a phenomenon has been well described with either a
      schizophrenic illness, severe mood disorders or periodic catatonia disorder. We
      aim to report a patient who had recurrent catatonia that responded to and
      required lorazepam for maintenance. METHODS: We describe the case of a 28 year
      old woman who had a history of recurrent catatonia that was unresponsive to most
      anti-psychotics, but who responded to high doses of lorazepam and needed long
      term lorazepam for maintenance. RESULTS AND CONCLUSION: Our patient met the
      criteria for a diagnosis of idiopathic catatonic disorder. Response to lorazepam
      suggests that a certain group of patients may require long-term treatment with
      lorazepam, especially those who may have down-regulation of GABA-A receptors.

PMID- 17558627
TI  - Lithium and topiramate association in the treatment of comorbid pathological
      gambling and bipolar disorder.

PMID- 17558629
TI  - Management of acute endosulfan poisoning in an organophosphate poisoning clinic.

PMID- 17558630
TI  - Comparison of bronchial responsiveness to ultrasonically nebulized distilled
      water (UNDW), methacholine, and ultrasonically nebulized distilled cold water
      (UDCW) in patients with sulfur mustard gas-induced asthma.
AB  - OBJECTIVE: To evaluate bronchial challenges using three different stimuli as
      screening tools for bronchial hyper-responsiveness in sulfur mustard gas-induced
      asthma. DESIGN: Randomized, cross-over clinical study. SETTING: University
      hospital. PATIENTS: Eighteen veterans with mustard gas-induced asthma and 18
      normal veterans as the control group. INTERVENTION: Pulmonary function tests and
      inhalation challenges with ultrasonically nebulized distilled water (UNDW),
      methacholine, and ultrasonically nebulized cold water (UNDCW) were performed on
      all patients and subjects. RESULTS: Six mustard gas-induced asthmatic veterans
      did not respond to a 20% in FEV(1) after distilled water (13.3%), and two of them
      (11.11%) did not respond with distilled cold water; all responded with
      methacholine. Only one healthy subject developed a PC20 FEV(1) after methacholine
      but did not with both distilled water and distilled cold water challenges. The
      asthmatic patients were sensitive to distilled water with a median PD20 of 7.24
      +/- 3.83 ml (range 2.54 ml to 15.83 ml), and sensitive to cold water with a
      median PD20 of 6.42 +/- 6.24 ml (range 1.92 ml to 25.15 ml). The median PC20
      methacholine was 1.90 +/- 1.88 mg/ml (range 0.14 mg/ml to 6.20 mg/ml). In
      patients with a positive response to the distilled water challenge test, no
      significant correlation was found between PC20 of methacholine and PD20 of
      distilled water (Rho = -0.34, p = 0.25), whereas in patients whose responses to
      distilled cold water (DCW) were positive, PD20 of distilled cold water (DCW)
      correlated well with PC20 of methacholine (Rho = -0.69, p = 0.006). CONCLUSION:
      Overall, the methacholine challenge test is the best method to distinguish these
      asthmatic patients from normal subjects in this study. When compared to the
      methacholine challenge, although the airway response to ultrasonically nebulized
      distilled cold water test was somewhat less sensitive, it may be used as a
      simple, fast, inexpensive, and relatively reliable method to predict the absence
      of asthma in sulfur mustard gas-induced asthma.

PMID- 17558631
TI  - Toxic Exposure Surveillance System (TESS)-based characterization of U.S. non
      native venomous snake exposures, 1995-2004.
AB  - BACKGROUND: Non-native (exotic) snake exposures in the United States have not
      been systematically characterized. METHODS: The Toxic Exposure Surveillance
      System (TESS) database of the American Association of Poison Control Centers was
      analyzed to quantify the number and types, demographic associations, clinical
      presentations, managements and outcomes, and the health resource utilization of
      non-native snake exposures. RESULTS: From 1995 through 2004, there were 399 non
      native exposures in the TESS database. Of these, 350 snakes (87%) were identified
      by genus and species, comprising at least 77 different varieties. Roughly equal
      percentages of snakes originated in Asia, Africa and Latin America, with a
      smaller number from the Middle-East, Australia, and Europe. Nearly half were
      viperids and a little more than a third were elapids. The vast majority of
      exposed individuals were adults. However, almost 15% were aged 17 years or less,
      and almost 7% were children aged 5 years or younger. Eighty-four percent were
      males. The vast majority of exposures occurred at the victim's own residence.
      Over 50% were evaluated at a healthcare facility, with 28.7% admitted to an ICU.
      Overall, 26% of patients were coded as receiving antivenom treatment. Coded
      outcomes were similar between viperid and elapid envenomations. There were three
      deaths, two involving viperid snakes and one elapid. Enhancements to the TESS
      database are required for better precision in and more complete characterization
      of non-native snake envenomations.

PMID- 17558632
TI  - Pre-Labor exposure to carbon monoxide: should the neonate be treated with
      hyperbaric oxygenation?
AB  - A woman was admitted to hospital in the 39th week of gestation due to syncope,
      followed by nausea and headache. The patient's history revealed a 10-hour,
      unintentional exposure to carbon monoxide (CO), secondary to burning charcoal for
      indoor heating. Because of monitored fetal distress, a cesarean section was
      performed. The newborn had an Apgar score of 4, 9, and 10 at 1, 5, and 10 minutes
      post-delivery, respectively. The 1-minute Apgar was low due to lack of
      spontaneous breathing, reduced tonus, bluish coloration, and reduced response to
      pain. The neonate's carboxyhemoglobin level seven hours post-CO exposure was 22%,
      and arterial pH was 7.28. Neurological examination 30 minutes after delivery
      showed no pathology. The neonate was treated with 100% normobaric oxygen for 12
      hours. We discuss the treatment options for fetal CO poisoning and specific
      considerations that had to be taken into account in the present case.

PMID- 17558633
TI  - Human poisoning in Thailand: The Ramathibodi Poison Center's experience (2001
      2004).
AB  - OBJECTIVE: To identify poisoning and toxic exposure pattern, severity, and
      clinical outcome in Thailand during 2001 to 2004. METHOD: This is a prospective
      study. All inquiries were registered, followed up, and verified. Interlocutors,
      poisons, patients' profiles, severity, and medical outcome after exposure or
      poisoning were analyzed. RESULTS: A total 14,428 events was suspected as human
      poisoning or exposure. After follow-up and verification, 98.9% were confirmed as
      poisoning or poison exposure. These involved 15,016 patients and accounted for
      6.0 per 100,000 populations per year. The vast majority of calls (92.4%) were
      from physicians. Pesticides, household products, and pharmaceutical products were
      the most common poisons involved in human exposure, which were 41.5%, 19.5%, and
      18.9%, respectively. Patients aged 0-6 years, teenagers and adults with 20-29
      years of age had the highest rates of exposure, which were 33.0, 24.5, and 10.5
      exposures per 100,000 per year, respectively. Unintentional accidental exposure
      is the major reason of exposure in children, but intentional suicide was the main
      reason of exposure in teenagers and adults. The death rate of all exposure was
      5.5%. Pesticides cause more severe clinical course and the highest death rate
      (10.0%). CONCLUSION: Features of poisoning in Thailand were different from those
      in Western countries. Pesticide poisoning was the major problem in Thailand.
      Intentional suicide was the major circumstance of poison exposure in adults, but
      accidental exposure was the major reason of exposure in children.

PMID- 17558634
TI  - Decline in pesticide poisonings in the United States from 1995 to 2004.
AB  - BACKGROUND: Trends in rates of unintentional pesticide illnesses and injuries by
      type were estimated for the United States from 1995 to 2004. METHODS: Poison
      Control Center data were examined for the years 1995 through 2004. Rates were
      calculated for pesticide type and selected pesticide classes based on estimated
      total United States population and proportion of population served. Pesticides as
      a proportion of poisonings to all substances over the years and vital statistics
      on deaths were examined to validate trends. RESULTS: Incidence rates of serious
      pesticide poisonings and injuries have declined 42% from 1995 to 2004 and death
      rates declined 62% over the same period. Selected, more toxic pesticides such as
      organophosphate and carbamate insecticides, strychnine rodenticides, and paraquat
      herbicides have shown greater declines, ranging 63% to 79%. CONCLUSIONS:
      Pesticide poisonings and injuries appear to have declined in the past decade.

PMID- 17558636
TI  - Hospital admission for accidental pesticide poisoning among adults of working age
      in England, 1998-2003.
AB  - AIMS: To explore the circumstances associated with hospital admission of adults
      of working age for accidental pesticide poisoning in England. METHODS: From
      Hospital Episode Statistics we identified all adults aged 16-69 years who
      completed hospital admissions nationally for accidental pesticide poisoning
      during April 1998 to March 2003. Further information was obtained through a
      postal questionnaire completed by the treating consultant. RESULTS:
      Questionnaires were returned for 62% of 237 identified admissions, including 89
      in which definite or possible accidental pesticide poisoning was confirmed. Fifty
      four percent of episodes arose from an identifiable mishap, and 26% from
      unsatisfactory storage or transport of pesticides. Only two incidents resulted
      from exposure to spray drift. Three patients needed intensive care, but none
      died. DISCUSSION: Serious accidental pesticide poisoning is rare among adults in
      England. There is an important contribution from poor storage of pesticides. Non
      occupational acute poisoning by spray drift is seldom if ever a cause of hospital
      admission.

PMID- 17558638
TI  - Effects of adenosine receptor antagonists on amitriptyline-induced vasodilation
      in rat isolated aorta.
AB  - BACKGROUND: Although we have previously demonstrated the beneficial effects of
      adenosine receptor antagonists in preventing cardiovascular toxicity of
      amitriptyline in rats, it is not clear whether adenosine receptors in heart or in
      vasculature are dominant. The aim of the current study was to investigate the
      role of adenosine A(2a) receptors on amitriptyline-induced vasodilation in rat
      isolated aorta. METHODS: After determining EC(80) of noradrenalin (NA) (the
      concentration of noradrenalin that produces 80% of maximal contractile response)
      as 10(-5)M, the IC(50) value of amitriptyline was measured in rat isolated aorta
      (the drug concentration causing a half- maximal inhibition of contractile
      responses to NA); IC(50) of amitriptyline was then compared in the presence of
      the DPCPX (a selective adenosine A(1) antagonist), CSC (a selective A(2a)
      antagonist) or DMSO (a solvent for adenosine antagonists). Statistical analysis
      was done using the Student t test. RESULTS: Amitriptyline-inhibited 49.9 +/- 3.7
      % contractile response to NA on aorta segments at 1.8 x 10(-5)M (IC(50)). While
      DPCPX increased amitriptyline-induced inhibition on contractile response to NA
      dose dependently, CSC decreased the contractile response to NA only at 10(-5)M.
      DMSO did not change amitriptyline-induced IC(50). CONCLUSION: Adenosine A(2a)
      receptor stimulation seems to be responsible partly for amitriptyline-induced
      vasodilation and hypotension since the adenosine A(1) antagonist, DPCPX,
      increased amitriptyline-induced vasodilation in rat isolated aorta.

PMID- 17558639
TI  - "Machiavellianism" and frontal dysfunction: evidence from Parkinson's disease.
AB  - INTRODUCTION: A number of reports have identified significant personality
      differences in patients with Parkinson's disease (PD) when compared with age
      matched controls. We hypothesised that these differences may be related to
      impairment in prefrontal inhibitory functions resulting in the expression of new
      "Machiavellian" personality traits. METHODS: Thirty-five patients with PD and 17
      age-matched controls were assessed with a set of neuropsychologic, personality
      and mood tests as well as the Mach IV scale, which measures a set of
      "Machiavellian" personality characteristics. RESULTS: PD patients with elevated
      Machiavellian traits ("high Machs") were selectively impaired on tests of
      prefrontal function relative to "low Mach" patients. In addition, while high
      Machs did not differ from low Machs in terms of age, educational level, Hoehn
      Yahr stage, mood function, or Mini Mental State Exam score, they indicated
      greater willingness to affiliate with a fictional Machiavellian character and
      scored significantly lower on the "cooperativeness" and "self-directedness"
      subscales of the Cloninger Temperament and Character Inventory. CONCLUSIONS: We
      suggest that (1) PD patients with frontal impairment are vulnerable to dramatic
      personality change, and (2) the frontal lobes are required for maintenance of
      prosocial personality traits.

PMID- 17558640
TI  - Overgeneral memory for public and autobiographical events in depression and
      schizophrenia.
AB  - INTRODUCTION: Memory for public and autobiographical events was investigated in
      people diagnosed with depression, schizophrenia, and a group of healthy controls.
      The aim was to determine whether the overgeneral memory effect emerged in
      clinical conditions other than depression and in memory domains other than
      autobiographical. METHODS: 36 participants, 12 in each group, were administered
      four measures comprising the Hospital Anxiety and Depression Scale, the
      Autobiographical Memory Test (AMT), the Autobiographical Memory Interview (AMI),
      and a Public Events Memory Test; the latter developed by the authors and based on
      the AMT. RESULTS: A pattern of overgeneral autobiographical memory retrieval was
      found in both clinical groups. A similar pattern in retrieval of public events
      was also found in people diagnosed with depression and schizophrenia, indicating
      that overgeneral memory was characteristic of neither clinical condition nor was
      it associated with a particular memory domain. CONCLUSIONS: The findings suggest
      that overgeneral memory retrieval may represent a fundamental flaw in memory that
      arises when resources are limited. These findings are discussed in light of
      current theories of overgeneral memory retrieval.

PMID- 17558641
TI  - Dissociating medication effects from learning and practice effects in a
      neurocognitive study of schizophrenia: Olanzapine versus haloperidol.
AB  - OBJECTIVE: To contrast the effect of a typical antipsychotic (haloperidol) and an
      atypical antipsychotic (olanzapine) on neurocognitive functioning in
      schizophrenia when learning and practice (LP) effects are controlled. METHODS:
      Two groups of participants were recruited, 27 schizophrenia patients in their
      first 5 years of illness and 13 normal controls. Prior to double-blind
      randomisation, all subjects were assessed on four occasions within 5 days
      (prerandomisation period) on the same neurocognitive battery. Repeated assessment
      prior to randomisation was chosen as a method to control for LP effects. Patients
      were then randomised to 56 days of treatment with haloperidol or olanzapine
      (postrandomisation). All subjects were assessed on neurocognitive measures at
      Days 28 and 56. RESULTS: LP effects were present during the prerandomisation
      period on motor tasks, verbal and visual short-term memory, attention, and on a
      measure of verbal working memory. There were no changes in performance for
      patients randomised to treatment with olanzapine or haloperidol or the normal
      control group during the postrandomisation period. CONCLUSIONS: Once LP effects
      are controlled, olanzapine and haloperidol do not affect performance on measures
      of motor functioning, verbal short-term memory, attention, verbal working memory,
      reaction time, visuospatial short-term memory, and visual working memory beyond
      that observed from LP effects.

PMID- 17558642
TI  - Exploring the perceptual characteristics of voice-hallucinations in deaf people.
AB  - INTRODUCTION: Previous research has not taken account of the possibility that
      deaf people will show greater heterogeneity in how they experience voice
      hallucinations due to individual differences in experience with language and
      residual hearing. This study aims to explore how deaf participants perceive voice
      hallucinations and whether the perceptual characteristics reported reflect
      individual experience with language and sensory input. METHOD: A statement
      sorting task generated data about perceptual characteristics of voice
      hallucinations for exploratory factor analysis. The sample included 27 deaf
      participants with experience of voice-hallucinations, and a range of hearing loss
      and language backgrounds. RESULTS: Perceptual characteristics of voice
      hallucinations map closely onto individual auditory experience. People born
      profoundly deaf loaded onto nonauditory factors. Deaf people with experience of
      hearing speech, through residual hearing, hearing aids, or predeafness
      experience, reported auditory features or uncertainty about mode of perception.
      CONCLUSIONS: This is the first study to systematically explore voice
      hallucinations in deaf people and to advance a model of subvocal articulation to
      account for such counterintuitive phenomena.

PMID- 17558643
TI  - Jumping to delusions? Paranoia, probabilistic reasoning, and need for closure.
AB  - INTRODUCTION: The present study was designed to replicate and extend the findings
      of Bentall and Swarbrick (2003). It was hypothesised that patients with a history
      of persecutory delusions would display higher need for closure and a more extreme
      jumping to conclusions bias than healthy control participants. METHODS: Twenty
      two patients with a history of persecutory delusions and nineteen healthy control
      participants were administered a probabilistic reasoning task, along with self
      report measures of depression and need for closure. RESULTS: The clinical group
      scored higher on need for closure than the controls, but showed no greater
      tendency to jump to conclusions. No relationship was found between need for
      closure and a jumping to conclusions bias. CONCLUSIONS: The results confirm an
      association between persecutory delusions and need for closure, yet suggest that
      persecutory delusions in an outpatient sample can be seen in the absence of a
      jumping to conclusions bias.

PMID- 17558645
TI  - Micromechanical modelling of cortical bone.
AB  - Cortical bone is a heterogeneous material with a complex hierarchical
      microstructure. In this work, unit cell finite element models were developed to
      investigate the effect of microstructural morphology on the macroscopic
      properties of cortical bone. The effect of lacunar and vascular porosities,
      percentage of osteonal bone and orientation of the Haversian system on the
      macroscopic elastic moduli and Poisson's ratios was investigated. The results
      presented provide relationships for applying more locally accurate material
      properties to larger scale and whole bone models of varying porosity. Analysis of
      the effect of the orientation of the Haversian system showed that its effects
      should not be neglected in larger scale models. This study also provides insight
      into how microstructural features effect local distributions and cause a strain
      magnification effect. Limitations in applying the unit cell methodology approach
      to bone are also discussed.

PMID- 17558646
TI  - Verification, validation and sensitivity studies in computational biomechanics.
AB  - Computational techniques and software for the analysis of problems in mechanics
      have naturally moved from their origins in the traditional engineering
      disciplines to the study of cell, tissue and organ biomechanics. Increasingly
      complex models have been developed to describe and predict the mechanical
      behavior of such biological systems. While the availability of advanced
      computational tools has led to exciting research advances in the field, the
      utility of these models is often the subject of criticism due to inadequate model
      verification and validation (V&V). The objective of this review is to present the
      concepts of verification, validation and sensitivity studies with regard to the
      construction, analysis and interpretation of models in computational
      biomechanics. Specific examples from the field are discussed. It is hoped that
      this review will serve as a guide to the use of V&V principles in the field of
      computational biomechanics, thereby improving the peer acceptance of studies that
      use computational modeling techniques.

PMID- 17558647
TI  - A real time hyperelastic tissue model.
AB  - Real-time soft tissue modeling has a potential application in medical training,
      procedure planning and image-guided therapy. This paper characterizes the
      mechanical properties of organ tissue using a hyperelastic material model, an
      approach which is then incorporated into a real-time finite element framework.
      While generalizable, in this paper we use the published mechanical properties of
      pig liver to characterize an example application. Specifically, we calibrate the
      parameters of an exponential model, with a least-squares method (LSM) using the
      assumption that the material is isotropic and incompressible in a uniaxial
      compression test. From the parameters obtained, the stress-strain curves
      generated from the LSM are compared to those from the corresponding computational
      model solved by ABAQUS and also to experimental data, resulting in mean errors of
      1.9 and 4.8%, respectively, which are considerably better than those obtained
      when employing the Neo-Hookean model. We demonstrate our approach through the
      simulation of a biopsy procedure, employing a tetrahedral mesh representation of
      human liver generated from a CT image. Using the material properties along with
      the geometric model, we develop a nonlinear finite element framework to simulate
      the behaviour of liver during an interventional procedure with a real-time
      performance achieved through the use of an interpolation approach.

PMID- 17558648
TI  - An experimental and theoretical approach of elasticity and viscoelasticity of
      compact and spongy bone with periodic homogenization.
AB  - An experimental study on samples from a fresh human femur highlighted the
      viscoelastic behaviour of bone. The memory aspect of the behaviour is weak
      compared to the elastic aspect. A theoretical and numerical approach based on the
      finite element method illustrates the existing bond between the structure and the
      micro behaviour on the one hand, and the macro behaviour on the other. The
      orthotropic elastic behaviour observed by various authors is shown numerically.
      The memory functions of compact and spongy bone are given. The numerical results
      illustrate the behaviour observed in the experiments.

PMID- 17558649
TI  - Sensitivity of the tibio-femoral response to finite element modeling parameters.
AB  - A generic finite element (FE) model of the lower limb was used to study the knee
      response in-vivo during a one-legged hop. The approach uses an explicit FE code
      and a combination of estimated muscle forces and measured three-dimensional tibio
      femoral kinematics and ground reaction force as input to the FE model. The
      sensitivity of the simulated tibio-femoral response to variations of key
      geometric and material parameters was investigated by performing a total of 38
      different simulations. The amplitudes of both kinematic and kinetic responses
      were affected by the change of these parameters. For the current approach, the
      results suggest that while cartilage mechanical and geometric properties are very
      important for the estimation of tibio-femoral cartilage pressure, they have
      limited effects on the overall kinematic response. The study may help to better
      define the relative importance of modeling parameters for the development of
      subject-specific models.

PMID- 17558650
TI  - A constitutive model for the periodontal ligament as a compressible transversely
      isotropic visco-hyperelastic tissue.
AB  - This study is devoted to the development of a non-linear anisotropic model for
      the human periodontal ligament (PDL). A thorough knowledge of the behaviour of
      the PDL is vital in understanding the mechanics of orthodontic tooth mobility,
      soft tissue response and proposed treatment plans. There is considerable evidence
      that the deformation of the PDL is the key factor determining the orthodontic
      tooth movement. The paper focuses on the biomechanical aspect of the behaviour of
      the PDL. In terms of continuous mechanics, the PDL may be treated as an
      anisotropic poro-visco-hyperelastic fibre-reinforced compressible material which
      is subject to large deformations and has an essentially non-linear behaviour.
      Furthermore, there are issues related to the non-linear tooth and PDL geometry. A
      new constitutive model for the PDL is proposed. The macroscopic continuum
      approach is used. The model is based on the non-linear large deformation theory,
      involving the Lagrangian description. The material is assumed to be compressible,
      visco-hyperelastic and transversely isotropic. A free-energy function is
      suggested that incorporates the properties. It also takes into account that the
      PDL behaves differently in tension and compression. The free-energy function and
      the associated constitutive equations involve several material parameters, which
      are to be evaluated from experimental strain-stress data available from the
      literature and the tooth movement experiments conducted by our team using novel
      optical motion analysis techniques.

PMID- 17558651
TI  - Finite element model of stresses in the anterior lens capsule of the eye.
AB  - Continuum biomechanics continues to aid in the design of clinical procedures and
      biomedical devices. Such design requires detailed information on the
      biomechanical properties of the tissues of interest as well as appropriate
      methods of analysis. In this paper, we use a fully nonlinear, virtual work based
      finite element method to study the normal stress field in the anterior lens
      capsule of the porcine eye. The analysis shows that recently measured regional
      variations in material symmetry may combine with regional variations in membrane
      thickness to yield a nearly uniform and equibiaxial stress field in normalcy.
      These findings are discussed in terms of potential implications to the underlying
      mechanobiology and in particular, in terms of perturbations in stress that result
      from cataract surgery, the most commonly performed surgical procedure in North
      America.

PMID- 17558653
TI  - Anti-citrulline antibodies in the diagnosis and prognosis of rheumatoid
      arthritis: evolving concepts.
AB  - Citrulline is a non-standard amino acid that can be incorporated into proteins
      only by post-translational modification of arginine by peptidylarginine deiminase
      (PAD) enzymes during a variety of biologic processes, including inflammation.
      Rheumatoid arthritis (RA) is an inflammatory autoimmune disease, with a
      prevalence of 0.3 to 1% worldwide, which leads to progressive joint erosion and
      substantial disability if not treated early. A reliable and specific test for a
      marker present early in the disease would be useful to identify RA patients prior
      to the occurrence of joint damage. A new group of autoantibodies, the anti-cyclic
      citrullinated peptide antibodies (anti-CCP), can be detected in up to 80% of
      patients with RA, are highly specific for the disease, and may be of value for
      both the diagnosis and the prognosis of RA. The fact that these antibodies may
      appear before the onset of the disease suggests a potential role in primary
      prevention. Interestingly, they may also play a role in the pathophysiology of
      this disabling disease. The process of citrullination, its physiologic role, and
      citrullination-related pathologies, as well as the use of anti-citrullinated
      protein antibody tests (ACPA) for the early diagnosis and prognosis of RA and
      their potential role in the pathophysiology of the disease, are discussed.

PMID- 17558654
TI  - Polyamines and the intestinal tract.
AB  - Owing to their high turnover, the intestinal mucosal cells have a particularly
      high requirement for polyamines. Therefore, they are an excellent charcol for the
      study of polyamine function in rapid physiological growth and differentiation.
      After a cursory introduction to the major aspects of polyamine metabolism,
      regulation, and mode of action, we discuss the contribution of the polyamines to
      the maintenance of normal gut function, the maturation of the intestinal mucosa,
      and its repair after injuries. Repletion of cellular polyamine pools with (D,L)-2
      (difluoromethyl)ornithine has considerably improved our understanding of how the
      polyamines are involved in the regulation of normal and neoplastic growth.
      Unfortunately, the attempts to exploit polyamine metabolism as a cancer
      therapeutic target have not yet been successful. However, the selective
      inactivation of ornithine decarboxylase appears to be a promising chemopreventive
      method in familial adenomatous polyposis. Presumably, it relies on the fact that
      ornithine decarboxylase is a critical regulator of the proliferative response of
      the protooncogene c-myc, but not of its apoptotic response.

PMID- 17558655
TI  - Simultaneous determination of B-group vitamins in enriched Brazilian dairy
      products.
AB  - In addition to serving as good natural sources of vitamin B(2), milk and milk
      products are currently being enriched with the vitamins B(1), B(2), B(6), and
      nicotinamide in Brazil. The objective of this research was to evaluate the levels
      of enrichment of these products according to their availability in supermarkets
      in the Campinas (SP, Brazil) region. The separation of the vitamins was carried
      out on a C 18 column with gradient elution with acetonitrile and aqueous phase.
      Detection of vitamins was effected in the ultraviolet region and quantification
      by an external standard. The levels of vitamin B(2) determined in powdered whole
      milk, skimmed milk powder, and one brand of flavored lactic beverage, were
      practically double those stated on the packages. The same occurred with vitamins
      B(6) and PP (nicotinic acid + nicotinamide), when determined in the same lactic
      beverage and with vitamin B(6), determined in acidified milk. The high levels of
      vitamin B(2), naturally present in whole milk, and the predominance of the free
      form, allowed for the determination of this vitamin in non-enriched milk.

PMID- 17558656
TI  - Implementation of physicochemical and sensory analysis in conjunction with
      multivariate analysis towards assessing olive oil authentication/adulteration.
AB  - The authenticity of products labeled as olive oils, and in particular as virgin
      olive oils, stands for a very important issue both in terms of its health and
      commercial aspects. In view of the continuously increasing interest in virgin
      olive oil therapeutic properties, the traditional methods of characterization and
      physical and sensory analysis were further enriched with more advanced and
      sophisticated methods such as HPLC-MS, HPLC-GC/C/IRMS, RPLC-GC, DEPT, and CSIA
      among others. The results of both traditional and "novel" methods were treated
      both by means of classical multivariate analysis (cluster, principal component,
      correspondence, canonical, and discriminant) and artificial intelligence methods
      showing that nowadays the adulteration of virgin olive oil with seed oil is
      detectable at very low percentages, sometimes even at less than 1%. Furthermore,
      the detection of geographical origin of olive oil is equally feasible and much
      more accurate in countries like Italy and Spain where databases of
      physical/chemical properties exist. However, this geographical origin
      classification can also be accomplished in the absence of such databases provided
      that an adequate number of oil samples are used and the parameters studied have
      "discriminating power."

PMID- 17558657
TI  - Interactions among infections, nutrients and xenobiotics.
AB  - During recent years there have been several incidents in which symptoms of
      disease have been linked to consumption of food contaminated by chemical
      substances (e.g., 2,3,7,8-tetrachlorodibenzo-p-dioxin, TCDD). Furthermore,
      outbreaks of infections in food-producing animals have attracted major attention
      regarding the safety of consumers, e.g., Bovine Spongiform Encephalitis (BSE) and
      influenza in chicken. As shown for several xenobiotics in an increasing number of
      experimental studies, even low-dose xenobiotic exposure may impair immune
      function over time, as well as microorganism virulence, resulting in more severe
      infectious diseases and associated complications. Moreover, during ongoing
      infection, xenobiotic uptake and distribution are often changed resulting in
      increased toxic insult to the host. The interactions among infectious agents,
      nutrients, and xenobiotics have thus become a developing concern and new avenue
      of research in food toxicology as well as in food-borne diseases. From a health
      perspective, in the risk assessment of xenobiotics in our food and environment,
      synergistic effects among microorganisms, nutrients, and xenobiotics will have to
      be considered. Otherwise, such effects may gradually change the disease panorama
      in society.

PMID- 17558658
TI  - Formation and reduction of acrylamide in Maillard reaction: a review based on the
      current state of knowledge.
AB  - The recent report of elevated acrylamide levels in heat processing foods evoked
      an international health alarm. Acrylamide, an acknowledged potential genetic and
      reproductive toxin with mutagenic and carcinogenic properties in experimental
      mammalians, has been found in various heat processing foods. Many original
      contributions reported their findings on the formation mechanism and possible
      reduction methods of acrylamide. The aim of this review article is to summarize
      the state-of-the-art about the formation and reduction of acrylamide in the
      Maillard reaction. This research progress includes mechanistic studies on the
      correlation between the Maillard reaction and acrylamide, the formation mechanism
      of acrylamide, the main pathways of formation and impact factors on formation
      including cultivars, storage temperature, storage time, heat temperature, heat
      time, environmental pH, concentration of precursors, effects of food matrixes,
      type of oil, etc. Meanwhile, primary mechanisms on the reduction of acrylamide as
      well as reduction pathways including material and processing related ways and use
      of exogenous chemical additives are systematically reviewed. The mitigation
      studies on acrylamide are also summarized by the Confederation of the Food and
      Drink Industries of the EU (CIAA) "Toolbox" approach.

PMID- 17558659
TI  - Survival and inactivation of Arcobacter spp., a current status and future
      prospect.
AB  - Arcobacter spp. has been isolated from food of animal origin (particularly meats)
      and from various kind of water. Despite its phylogenetically related neighbor
      Campylobacter, Arcobacter is regarded as an emerging foodborne pathogen. Since
      Arcobacter differs in its phenotypic characteristics, the physical and chemical
      treatments designed for elimination of campylobacters from food and environment
      needs to be verified. This review focuses on the occurrence, and mainly on
      susceptibility to various physical and chemical treatments for inactivation of
      Arcobacter spp. The existing studies have been critically discussed and new
      challenges were proposed for further studies.

PMID- 17558660
TI  - Botulism diagnostics: from clinical symptoms to in vitro assays.
AB  - Botulinum neurotoxin (BoNT), which cause the deadly neuroparalytic disease,
      botulism, is the most toxic substance known to man. BoNT can be used as potential
      bioterrorism agents, and therefore, pose great threat to national security and
      public health. Rapid and sensitive detection of BoNTs using molecular and
      biochemical techniques is an essential component in the diagnosis of botulism,
      and is yet to be achieved. The most sensitive and widely accepted assay method
      for BoNTs is mouse bioassay, which takes 4 days to complete. This clearly can not
      meet the need for clinical diagnosis of botulism, botulinum detection in field
      conditions, and screening of large scale samples. Consequently, the clinical
      diagnosis of botulism relies on the clinical symptom development, thus limiting
      the effectiveness of antitoxin treatment. In response to this critical need, many
      in vitro methods for BoNT detection are under development. This review is focused
      on recently developed in vitro detection methods for BoNTs, and emerging new
      technologies with potential for sensitive and rapid in vitro diagnostics for
      botulism.

PMID- 17558661
TI  - Acetoin metabolism in bacteria.
AB  - Acetoin is an important physiological metabolite excreted by many microorganisms.
      The excretion of acetoin, which can be diagnosed by the Voges Proskauer test and
      serves as a microbial classification marker, has its vital physiological meanings
      to these microbes mainly including avoiding acification, participating in the
      regulation of NAD/NADH ratio, and storaging carbon. The well-known anabolism of
      acetoin involves alpha-acetolactat synthase and alpha-acetolactate decarboxylase;
      yet its catabolism still contains some differing views, although much attention
      has been focused on it and great advances have been achieved. Current findings in
      catabolite control protein A (CcpA) mediated carbon catabolite repression may
      provide a fuller understanding of the control mechanism in bacteria. In this
      review, we first examine the acetoin synthesis pathways and its physiological
      meanings and relevancies; then we discuss the relationship between the two
      conflicting acetoin cleavage pathways, the enzymes of the acetoin dehydrogenase
      enzyme system, major genes involved in acetoin degradation, and the CcpA mediated
      acetoin catabolite repression pathway; in the end we discuss the genetic
      engineering progresses concerning applications. To date, this is the first
      integrated review on acetoin metabolism in bacteria, especially with regard to
      catabolic aspects. The apperception of the generation and dissimilation of
      acetoin in bacteria will help provide a better understanding of microbial
      strategies in the struggle for resources, which will consequently better serve
      the utilization of these microbes.

PMID- 17558663
TI  - Driving violations observed: an Australian study.
AB  - This study analyses 2,765 cases of driving behaviours in three Australian states 
      New South Wales, Queensland and Victoria. Data were gathered from in-car
      coordinated video and audio recording sequences in free-flowing traffic along two
      , three- and four-lane highways with varying speed limits on all days of the week
      in daylight and fine weather conditions. Explanatory variables included driver
      age group and gender, passenger characteristics and vehicle age and type.
      Response variables included driving violations and other driving behaviours,
      including lane use, speeding, close following (tailgating), driver's hands
      position and mobile phone use. Data were analysed qualitatively and
      quantitatively. By focusing upon vehicle and driver characteristics, and their
      impact on driving behaviours, including identified violations, this study
      explores some implications both for future research and for traffic policy
      makers.

PMID- 17558664
TI  - Driver headway: how close is too close on a motorway?
AB  - Driver headway has recently become an important question with much attention
      being given to unsafe headway or 'tailgating'. This paper reviews a series of
      recent studies undertaken at the University of Southampton, which have sought to
      measure and model distance keeping, demonstrating how following distance depends
      on a wide range of factors, some of which are only recently being explored. These
      include variations in following distance for any particular driver and the
      relationship with time to collision, variations in following distances of drivers
      of differing nationalities and the ability of the driver to 'read the road
      ahead', which may be affected by interaction with different vehicle types. It is
      demonstrated that providing clear unequivocal statements regarding car following
      and safety levels, even after such studies, is still far from straightforward.

PMID- 17558665
TI  - Car driver speed choice in Scotland.
AB  - Drivers who commit driving violations, such as speeding, crash more. Driving
      violations reduce safety margins amplifying the impact of driver errors. Speed is
      placed in the context of car use and its attractions. It is argued that speed
      choice results from the interaction of opportunities, obligations and
      inclinations. Data from large-scale surveys of Scottish car drivers support this
      and show that many drivers in Scotland prefer to drive at or below the speed
      limit and that many say they are currently cutting their normal driving speed.
      Suggestions for promoting safer and more sustainable speed choices are made.

PMID- 17558666
TI  - Changing drivers' minds: the evaluation of an advanced driver coaching system.
AB  - This paper reports on the study of an advanced driver coaching system. The study
      distinguishes between different types of post-licensure programmes in order to
      explore a system based on a model of identifying and responding to hazards,
      called 'information, position, speed, gear and acceleration' (IPSGA). Previous
      literature has been sceptical about the benefits of advanced driver education;
      thus, the current study was designed to control for the effects of coaching
      drivers in the 'IPSGA' system (the treatment group) against the effects of being
      accompanied (control group 1), as well as the mere effects of time (control group
      2). Measures were taken before the driver coaching began (as a baseline measure)
      and again after 8 weeks (to see if any changes had occurred). These measures
      included driver knowledge via a post-drive interview, observations of driving
      skill and driver attitude using a locus of control scale. The results suggest
      that advanced driver coaching using the IPSGA system had a beneficial effect on
      all of these measures. Drivers in the coaching condition improved their situation
      awareness, driving skills and reduced attributions of external locus of control.
      The study lends support to the case for one-to-one individualized driver coaching
      using a systematic model of driving.

PMID- 17558667
TI  - Visual attention and the transition from novice to advanced driver.
AB  - Inexperienced drivers are particularly vulnerable to road traffic accidents, and
      inattention emerges as a factor in these accidents. What do these drivers attend
      to and how can their observation skills be developed? When drivers scan the road
      around them, differences are observed as function of driving experience and
      training, with experienced drivers increasing their visual scanning on roadways
      of increasing complexity. Trained police drivers showed this effect of increased
      scanning even more than experienced drivers. This suggests that the driver's
      understanding of the task develops with experience, such that roads that demand
      increased monitoring (e.g. interweaving traffic on a multi-lane highway) receive
      more extensive scanning than roads that are simpler (e.g. light traffic on a
      straight rural road). Novice drivers do not show this sensitivity to road
      complexity, suggesting that they fail to attend to potential dangers involving
      the behaviour of other road users. Encouragingly, a simple training intervention
      can increase the visual scanning of novices.

PMID- 17558668
TI  - Anticipating the content and circumstances of skill transfer: unrealistic
      expectations of driver training and graduated licensing?
AB  - There is substantial evidence that driving skills improve during driver training,
      but the long-term safety benefit of such formal training remains unproven.
      Restricting the exposure of newly licensed drivers to more hazardous driving
      circumstances, as in graduated driver licensing (GDL) regimes, demonstrably
      reduces crash risk, but drivers remain at risk after the restrictions are eased.
      GDL and most other licensing regimes advocate increased basic training and
      practice, but thereafter require neither advanced training nor systematic
      increase in exposure to risk. This assumes that basic skills acquired during
      formal training will transfer positively to new and more demanding traffic
      circumstances. This paper reviews the theoretical basis for these assumptions and
      offers a way of systematically identifying the extent of transfer desired. It is
      concluded that there is little theoretical or empirical foundation for the
      supposition that what is learned during or after training will have a safety
      benefit in later driving.

PMID- 17558669
TI  - The influence of distraction and driving context on driver response to imperfect
      collision warning systems.
AB  - Automotive collision warning systems (CWS) can enhance hazard identification and
      management. However, false alarms (FAs), which occur as a random activation of
      the system not corresponding to a threat and not interpretable by the driver, and
      unnecessary alarms (UAs), which occur in situations judged hazardous by the
      algorithm but not by the driver, may limit CWS effectiveness. A driving simulator
      was used to investigate the influence of CWS (accurate, UA, FA, none) and
      distraction on driver performance during non-critical and critical events. FAs
      and UAs differentially influenced trust and compliance. FAs diminished trust and
      compliance, whereas the context associated with UAs fostered trust and compliance
      during subsequent events. This study suggests current warning descriptions based
      on signal detection theory need to be expanded to represent how different types
      of alarms affect drivers.

PMID- 17558670
TI  - A framework for the design of ambulance sirens.
AB  - Ambulance sirens are essential for assisting the safe and rapid arrival of an
      ambulance at the scene of an emergency. In this study, the parameters upon which
      sirens may be designed were examined and a framework for emergency vehicle siren
      design was proposed. Validity for the framework was supported through acoustic
      measurements and the evaluation of ambulance transit times over 240 emergency
      runs using two different siren systems. Modifying existing siren sounds to add
      high frequency content would improve vehicle penetration, detectability and sound
      localization cues, and mounting the siren behind the radiator grill, rather than
      on the light bar or under the wheel arch, would provide less unwanted noise while
      maintaining or improving the effective distance in front of the vehicle.
      Ultimately, these considerations will benefit any new attempt to design auditory
      warnings for the emergency services.

PMID- 17558671
TI  - Vehicle automation: a remedy for driver stress?
AB  - The present study addressed the effects of stress, vehicle automation and
      subjective state on driver performance and mood in a simulated driving task. A
      total of 168 college students participated. Participants in the stress-induction
      condition completed a 'winter' drive, which included periodic loss of control
      episodes. Participants in the no-stress-induction condition were not exposed to
      loss of control. An additional, independent manipulation of vehicle speed was
      also conducted, consisting of two control conditions requiring manual speed
      regulation and a third in which vehicle speed was automatically regulated by the
      simulation. Stress and automation both influenced subjective distress, but the
      two factors did not interact. Driver performance data indicated that vehicle
      automation impacted performance similarly in the stress and no-stress conditions.
      Individual differences in subjective stress response and performance were also
      investigated. Resource theory provides a framework that partially but not
      completely explains the relationship between vehicle automation and driver
      stress. Implications for driver workload, safety and training are discussed.

PMID- 17558672
TI  - What's skill got to do with it? Vehicle automation and driver mental workload.
AB  - Previous research has found that vehicle automation systems can reduce driver
      mental workload, with implications for attentional resources that can be
      detrimental to performance. The present paper considers how the development of
      automaticity within the driving task may influence performance in underload
      situations. Driver skill and vehicle automation were manipulated in a driving
      simulator, with four levels of each variable. Mental workload was assessed using
      a secondary task measure and eye movements were recorded to infer attentional
      capacity. The effects of automation on driver mental workload were quite robust
      across skill levels, but the most intriguing findings were from the eye movement
      data. It was found that, with little exception, attentional capacity and mental
      workload were directly related at all levels of driver skill, consistent with
      earlier studies. The results are discussed with reference to applied theories of
      cognition and the design of automation.

PMID- 17558673
TI  - Examining cognitive interference and adaptive safety behaviours in tactical
      vehicle control.
AB  - Concurrent mental workload degrades some aspects of driving performance, but
      drivers might be able to modify their behaviour adaptively to accommodate
      cognitive impairments. For example, they might maintain longer vehicle headway in
      dual-task conditions to compensate for slowed response times. Studies documenting
      such adaptive behaviours typically use steady-state driving scenarios such as car
      following. Yet, driving often involves tactical control situations in which
      drivers need to monitor multiple aspects of their traffic environment and to
      accommodate changing goals. In two simulator experiments, this study examined the
      impact of mental workload on safety margins (distances) that drivers keep when
      engaged in a tactical control task: passing other vehicles. Although drivers did
      increase their headway adaptively when engaged in steady-state car following
      (experiment 2), they did not adapt their behaviour to accommodate cognitive load
      when performing tactical control manoeuvres. Implications of this difference
      between steady-state and tactical control driving contexts, both for driving
      research and for driving safety, are discussed.

PMID- 17558674
TI  - Situation awareness and driving performance in a simulated navigation task.
AB  - The objective of this study was to identify task and vehicle factors that may
      affect driver situation awareness (SA) and its relationship to performance,
      particularly in strategic (navigation) tasks. An experiment was conducted to
      assess the effects of in-vehicle navigation aids and reliability on driver SA and
      performance in a simulated navigation task. A total of 20 participants drove a
      virtual car and navigated a large virtual suburb. They were required to follow
      traffic signs and navigation directions from either a human aid via a mobile
      phone or an automated aid presented on a laptop. The navigation aids operated
      under three different levels of information reliability (100%, 80% and 60%). A
      control condition was used in which each aid presented a telemarketing survey and
      participants navigated using a map. Results revealed perfect navigation
      information generally improved driver SA and performance compared to unreliable
      navigation information and the control condition (task-irrelevant information).
      In-vehicle automation appears to mediate the relationship of driver SA to
      performance in terms of operational and strategic (navigation) behaviours. The
      findings of this work support consideration of driver SA in the design of future
      vehicle automation for navigation tasks.

PMID- 17558675
TI  - Breath condensate levels of 8-isoprostane and leukotriene B4 after ozone
      inhalation are greater in sensitive versus nonsensitive subjects.
AB  - Ozone (O3) inhalation induces pulmonary function decrements and inflammation. The
      present study was designed to determine if a relationship exists between O3
      induced pulmonary function changes and the presence of inflammatory markers as
      measured in exhaled breath condensates (EBCs) obtained from O3-sensitive and
      nonsensitive human subjects. Eight healthy adult volunteers (4 males/4 females,
      age 18 to 30 years) were studied, characterized as to their ozone sensitivity and
      placed into 2 groups (sensitive and nonsensitive) with each group having 2 males
      and 2 females. Subjects completed a 20-minute EBC collection and pulmonary
      function test (PFT) prior to a single 60-minute bout of cycle ergometer exercise
      (V(E) = 50-55 L/min) while breathing filtered air (FA) or 0.35 ppm O3. Subjective
      symptom scores (SSSs) were collected at 6, 20, 40, and 60 minutes during
      exposure. An immediate postexposure PFT was performed followed by an EBC
      collection. Subjective symptom scores, EBCs, and PFTs were collected at 1, 4 and
      8 hours post exposure. EBCs were analyzed for prostaglandin E2 (PGE2),
      leukotriene B4 (LTB4), 8-isoprostane, and total nitric oxide (NO) metabolites
      (nitrate + nitrite content). Sensitive subjects, breathing O3, had significantly
      greater functional decrements in PFTs, increased SSSs, and increased rapid
      shallow breathing as well as elevated levels of 8-isoprostane and LTB4 in EBCs
      compared to those breathing FA. In addition, there were significant increases in
      nitrate + nitrite content in both sensitive and nonsensitive subjects breathing
      O3 compared to FA. These results indicate that sensitive subjects have elevated
      arachidonic acid metabolites in EBCs compared to nonsensitive subjects after O3
      inhalation.

PMID- 17558676
TI  - German cockroach frass proteases cleave pro-matrix metalloproteinase-9.
AB  - Matrix metalloproteinase (MMP)-9, secreted as pro-MMP-9, is cleaved by serine
      proteases at the N-terminus to generate active MMP-9. Pro-MMP-9 has been found in
      the bronchoalveolar lavage fluid of patients with asthma. Because many inhaled
      aeroallergens contain active proteases, the authors sought to determine whether
      German cockroach (GC) fecal remnants (frass) and house dust mite (HDM) were able
      to cleave pro-MMP-9. Treatment of recombinant human (rh) pro-MMP-9 with GC frass
      resulted in a dose- and time-dependent cleavage. This was abrogated by
      pretreating frass with an inhibitor of serine, but not cysteine protease
      activity. GC frass also induced cleavage of pro-MMP-9 from primary human
      neutrophils dependent on the active serine proteases in GC frass. HDM was less
      potent at cleaving pro-MMP-9. Alpha1-antitrypsin (A1AT), a naturally occurring
      protease inhibitor, attenuated GC frass-induced cleavage of pro-MMP-9. A1AT
      partially inactivated the serine protease activity in GC frass, while GC frass
      cleaved A1AT in a dose- and time-dependent manner. These data suggest that GC
      frass-derived serine proteases could regulate the activity of MMP-9 and that A1AT
      may play an important role in modulating GC frass activity in vivo. These data
      suggest a mechanism by which inhalation of GC frass could regulate airway
      remodeling through the activation of pro-MMP-9.

PMID- 17558677
TI  - Substance P up-regulates matrix metalloproteinase-1 and down-regulates collagen
      in human lung fibroblast.
AB  - Substance P is involved in inflammatory processes, but its effect on
      extracellular matrix metabolism has not been studied; therefore, the authors
      evaluated its effect on collagen synthesis and degradation, expression of pro
      alpha1(I) collagen, matrix metalloproteinase-1 and -2, and tissue inhibitor of
      metalloproteinase-1 and -2 in normal human lung fibroblast strains. Substance P
      induced a decrease in collagen biosynthesis, concomitant to a down-regulation of
      pro-alpha1(I) collagen mRNA. In contrast, an increase in collagen degradation was
      observed, accompanied with an up-regulation of matrix metalloproteinase-1.
      Substance P did not influence tissue inhibitor of metalloproteinase-1 and -2 or
      matrix metalloproteinase-2 expression. The results suggest that substance P
      participates in extracellular matrix metabolism.

PMID- 17558679
TI  - Expression of specific protein kinase C (PKC) isoforms and ligand-specific
      activation of PKCalpha in late gestation fetal lung.
AB  - Epidermal growth factor receptor signaling plays an important role in lung
      maturation. The authors hypothesized that specific protein kinase C (PKC)
      isoforms are expressed and activated by epidermal growth factor (EGF) and
      transforming growth factor alpha (TGFalpha) (EGF receptor [EGFR] ligands) in
      fetal lung fibroblasts. The authors found 4 PKC isoforms expressed in gestational
      day 19 (d19) fetal rat lung fibroblasts, and focused on PKCalpha because of its
      developmental expression pattern. PKCalpha immunolocalization in d17, d19, and
      d21 fetal lung fibroblasts was similar to EGFR. PKCalpha expression decreased
      with lung maturation. EGF, but not TGFalpha, stimulated PKCalpha activation and
      membrane translocation. Further studies of PKCalpha functions in fetal lung
      development are clearly needed.

PMID- 17558678
TI  - A micro-computed tomography-based method for the measurement of pulmonary
      compliance in healthy and bleomycin-exposed mice.
AB  - Micro-computed tomography (microCT) is being increasingly used to examine small
      animal models of pulmonary injury. The authors have developed a microCT technique
      suitable for the determination of pulmonary compliance in injured mice. Lung
      volumes in normal mice were radiographically determined at end-inspiration and
      end-expiration and pulmonary compliance was calculated at 2 time points 2 weeks
      apart, whereas a second group of mice were given bleomycin and imaged 3 weeks
      following drug administration. Compliance measurements were validated using a
      commercially available ventilator system. MicroCT pulmonary compliance
      measurements are suitable for longitudinal measurements, and correlate with
      physiologic measurements of pulmonary compliance.

PMID- 17558680
TI  - What is the best first-step therapeutic approach in treating anovulatory
      infertility in patients with polycystic ovary syndrome? Questions that are still
      unanswered.

PMID- 17558681
TI  - Hirsutism and hyperandrogenism associated with hyperreactio luteinalis in a
      singleton pregnancy: a case report.
AB  - The incidence of hyperandrogenism during pregnancy is low, although the incidence
      of some of the ovarian diseases that can cause it is higher. Hyperreactio
      luteinalis is a rare benign condition that may mimic ovarian and trophoblastic
      malignancies. A 23-year-old woman at 20 weeks' gestational age presenting with
      severe hirsutism and ovarian masses was treated conservatively and subsequently
      gave birth to a healthy female neonate. Final diagnosis was hyperreactio
      luteinalis. Conservative management with close monitoring of patients with
      hyperreactio luteinalis represents the best approach in such rare cases.
      Counseling should be provided to reassure the patient as to the transient effects
      of hyperandrogenism on the mother and the fetus.

PMID- 17558682
TI  - A patient with combined polycystic ovary syndrome and autoimmune polyglandular
      syndrome type 2.
AB  - We report a patient with combined polycystic ovary syndrome (PCOS) and autoimmune
      polyglandular syndrome (APS) type 2. A 26-year-old female presented with
      polyuria, polydipsia and acute weight loss. She was diagnosed with: (1) type 1
      diabetes, with hyperglycemia, impaired insulin secretion, and positive
      autoantibodies for GAD-65 and IA-2; (2) autoimmune thyroiditis, with
      hypothyroidism, positive anti-microsomal and antithyroglobulin antibodies; and
      (3) PCOS, with hyperandrogenic signs that had developed 5 years earlier,
      amenorrhea for the previous 6 months, and characteristic multiple microcystic
      appearance of both ovaries on ultrasonography. She is being treated with multiple
      subcutaneous insulin injections, thyroxine replacement, and cyclic
      medroxyprogesterone for the aforementioned diseases, respectively. Although
      several investigations have reported a relationship between PCOS and the
      individual components of APS, this is the first report of both syndromes
      occurring simultaneously. Potential mechanisms for their interrelation and the
      possibility that PCOS is an autoimmune disease are discussed.

PMID- 17558683
TI  - Allopregnanolone decrease with symptom improvement during placebo and
      gonadotropin-releasing hormone agonist treatment in women with severe
      premenstrual syndrome.
AB  - BACKGROUND: Neurosteroids such as allopregnanolone and pregnanolone are suggested
      to be of importance for the pathophysiology of premenstrual dysphoric disorder.
      The aim of this study was to investigate whether the luteal-phase serum
      concentrations of these neurosteroids are associated with improvement of
      premenstrual symptoms in 12 women with severe premenstrual syndrome after
      treatment with low-dose gonadotropin-releasing hormone agonist and placebo.
      METHODS: Daily ratings for mood and physical symptoms were made prior to
      treatment and throughout the study. Serum progesterone, allopregnanolone and
      pregnanolone were assessed in the luteal phase (cycle day -9 to cycle day -1).
      Based on their symptom ratings, subjects were grouped as either buserelin
      responders (n = 6) or placebo responders (n = 6). RESULTS: Buserelin responders
      displayed decreased levels of allopregnanolone (p < 0.05) and progesterone (p <
      0.05) in parallel with improvement of symptoms. During the placebo treatment, the
      placebo responders had lower serum allopregnanolone concentrations than buserelin
      responders (p < 0.05). This was associated with improvement in symptoms compared
      with pre-treatment ratings. CONCLUSION: Treatment response, whether induced by
      buserelin or placebo, appears to be associated with a decrease in
      allopregnanolone concentration.

PMID- 17558684
TI  - Polycystic ovary syndrome and hyperprolactinemia are distinct entities.
AB  - The aims of the present study were to identify the cause of hyperprolactinemia in
      polycystic ovary syndrome (PCOS) and to compare prolactin (PRL) levels between
      PCOS women without hyperprolactinemia and women with insulin resistance and
      without PCOS. A group of 82 women (age: 27.1 +/- 7.6 years) with PCOS was
      included in the study. Their PRL levels were measured and compared with those of
      women with insulin resistance without PCOS (controls; n = 42; age: 29.2 +/- 8.2
      years). Among the 82 PCOS women, 13 (16%) presented high PRL levels (103.9 +/-
      136.0 microg/l). The causes of hyperprolactinemia were: pituitary tumor
      (responding to cabergoline) in nine cases (69%; PRL range: 28.6 - 538 microg/l);
      oral hormonal contraceptive treatment in two cases (15%; PRL: 46 and 55 microg/l,
      respectively); and use of buspirone and tianeptine in one case (8%; PRL: 37.1
      microg/l); one case (8%; PRL: 34.4 microg/l) had macroprolactinemia. In drug
      induced hyperprolactinemic patients PRL levels normalized after treatment
      interruption. The average PRL level in the 69 remaining patients was 12.1 +/- 5.5
      microg/l, a value not statistically different from that of the control group
      (11.8 +/- 4.9 microg/l). This result leads us to conclude that PCOS patients with
      increased PRL levels must be investigated for other causes of hyperprolactinemia,
      because hyperprolactinemia is not a clinical manifestation of PCOS.

PMID- 17558685
TI  - Metformin in normal-weight hirsute women with polycystic ovary syndrome with
      normal insulin sensitivity.
AB  - Fifteen normal-weight (body mass index (BMI) 21.50 +/- 1.65 kg/m(2)) hirsute
      women with polycystic ovary syndrome and normal insulin sensitivity were treated
      with 850 mg metformin orally, three times daily, for 4 months. Before and at the
      end of the treatment, clinical data as well as serum concentrations of sex
      steroid hormones, gonadotropins, fasting plasma glucose and insulin, insulin
      resistance - homeostasis model assessment (HOMA-IR), carbohydrate tolerance and
      the area under the curve for insulin (AUC(insulin)) were analyzed. Three patients
      withdrew from the study. Seven of the remaining 12 patients presented menstrual
      pattern improvement, followed by ovulatory cycles at the end of the treatment
      period. There were no changes in BMI and hirsutism score. A significant (p <
      0.05) decrease in luteinizing hormone (LH) (from 8.18 +/- 4.34 to 5.05 +/- 1.53
      IU/ml), testosterone (from 104.66 +/- 27.54 to 82.00 +/- 23.05 ng/dl), fasting
      insulin (from 9.66 +/- 4.79 to 7.83 +/- 3.06 microIU/ml), AUC(insulin) (from 9239
      +/- 3285 to 7660 +/- 2565 microUI/ml x min) and HOMA-IR (from 2.15 +/- 1.2 to
      1.67 +/- 0.74), and a significant increase in follicle-stimulating hormone (FSH)
      (from 4.05 +/- 1.53 to 5.96 +/- 2.13 IU/ml), were observed at the end of the
      treatment period. A higher LH and a lower FSH predicted clinical improvement,
      while basal insulin and AUC(insulin) showed lower predictive value.

PMID- 17558686
TI  - Subclinical hypothyroidism and thyroid autoimmunity in women with infertility.
AB  - OBJECTIVE: To determine the prevalence of different subclinical hypothyroidism
      (SH) grades and thyroid autoimmunity (TAI) in infertile women. DESIGN:
      Retrospective study. Setting. Endocrinology division of a public hospital in
      Argentina. PATIENTS: Group I comprised 244 women consulting on infertility (>1
      year without pregnancy); Group C (controls) comprised 155 healthy women with
      confirmed fertility. INTERVENTION: Thyroid-stimulating hormone and thyroid
      peroxidase antibodies were measured in all patients, and a thyrotropin-releasing
      hormone (TRH) stimulation test was performed in 71 patients to diagnose SH grade
      1. The pregnancy rate in hypothyroid women on levothyroxine treatment was also
      evaluated. RESULTS: SH was diagnosed in 13.9% of the patients in Group I and in
      3.9% of Group C (p < 0.002). The TRH stimulation test was useful to detect SH
      grade 1 in 12.7% of the infertile patients. Patients with precocious ovarian
      failure, tubal disturbances and ovulatory dysfunction presented higher SH rates
      (40.0, 18.2 and 15.4%, respectively) than control patients (p < 0.0001, p < 0.002
      and p < 0.003). No significant difference in TAI prevalence was shown in Group I
      relative to Group C. Pregnancy rate of 44.1% was achieved under levothyroxine
      treatment. CONCLUSIONS: We observed a higher prevalence of SH, but not of TAI, in
      patients with infertility. Our results support thyroid screening in women with
      reproductive failure.

PMID- 17558687
TI  - Undetectable basal ovarian stromal blood flow in infertile women is related to
      low ovarian reserve.
AB  - To gain insight into the physiological significance of basal ovarian stromal
      blood flow and to assess whether its detection ability is related to ovarian
      reserve in infertility patients undergoing in vitro fertilization (IVF) - embryo
      transfer (ET) treatment. Thirty two consecutive infertile women scheduled for IVF
      ET treatment were prospectively evaluated. Basal ovarian hormonal, ovarian volume
      and stromal blood flow studies were performed on day 3 of a natural cycle before
      treatment. The performer of the ultrasound studies was blinded to the clinical
      data. Women in the study were divided into two groups in accordance with
      estradiol level on the day of administration of human chorionic gonadotropin. Day
      3 follicle-stimulating hormone and ovarian volume were significantly poorer in
      the women with low (group A) as compared with good (group B) ovarian reserve.
      Likewise, the numbers of follicles > or =14 mm in diameter, oocytes retrieved and
      embryos achieved were significantly lower in group A than group B. Six clinical
      pregnancies were obtained in group B, whereas no pregnancy was obtained in group
      A. Nine out of the 15 (60%) women in group A had undetectable basal stromal blood
      flow in at least one of the ovaries, whereas only one of the 17 (6%) women in
      group B had undetectable flow (p < 0.002). Basal stromal peak systolic blood flow
      velocity, pulsatility index and resistance index mean values did not differ
      significantly between the two groups. We conclude that undetectable basal ovarian
      stromal blood flow in at least one ovary is related to low ovarian reserve in
      infertile women undergoing IVF-ET. It seems that undetectable basal stromal blood
      flow is not solely a technical issue, but rather linked to the pathophysiology of
      ovarian aging.

PMID- 17558688
TI  - Protection of ovarian function and fertility using a combination of gonadotropin
      releasing hormone (GnRH) agonist and GnRH antagonist during cancer treatment in
      young females.
AB  - Cytotoxic treatment can cause early loss of ovarian function associated with loss
      of fertility in younger women. To investigate if co-treatment with a combination
      of gonadotropin-releasing hormone (GnRH) agonist and GnRH antagonist may be
      useful in preserving ovarian function and fertility in younger women during
      chemotherapy, we prospectively observed nine young patients receiving different
      chemotherapies for various malignant diseases and other severe medical conditions
      who also received simultaneous GnRH agonist and GnRH antagonist. Mean age of the
      patients was 26.56 +/- 8.78 years, all were < or =35 years old. Eight (88.9%)
      patients regained normal basal hormonal profile within 3 - 6 months after the
      completion of chemotherapy. Median level of follicle-stimulating hormone,
      luteinizing hormone and estradiol was 6.3 +/- 8.8 U/l, 8.2 +/- 25.4 U/l and 118.0
      +/- 130.8 pg/ml, respectively. Eight (88.9%) patients resumed spontaneous menses
      within 3 - 11 months following discontinuation of chemotherapy. Two (22.2%)
      patients conceived: one spontaneously, and the second following induction of
      ovulation by injection of gonadotropins. It seems that combined usage of GnRH
      agonist and GnRH antagonist during chemotherapy may be useful in preserving
      ovarian function and fertility in a group of young females receiving chemotherapy
      treatment.

PMID- 17558689
TI  - Galanin concentrations in maternal circulation, amniotic fluid and umbilical cord
      blood during term labor: relationship with maternal body mass and neonatal birth
      weight.
AB  - BACKGROUND: Galanin is a hypothalamic regulatory peptide involved in the
      regulation of appetite. It is synthesized by the nervous system, anterior
      pituitary gland, adrenal medulla, pancreas, intestine and placenta. Placental
      secretion of galanin has until now only been investigated in animals.
      Additionally, galanin concentration has not been assessed in umbilical cord blood
      and amniotic fluid. PATIENTS AND METHODS: Galanin concentrations were measured in
      maternal circulation before term delivery, in cord blood and in amniotic fluid of
      45 healthy pregnant women (gestational age 38 - 40 gestational weeks). The
      control group consisted of 26 normally menstruating healthy women. RESULTS:
      Plasma galanin concentrations were found to be similar in pregnant healthy women
      before term delivery (20.8 +/- 1.9 pg/ml) and non-pregnant women (19.0 +/- 1.7
      pg/ml). Galanin concentration in umbilical cord blood (26.5 +/- 2.2 pg/ml) was
      significantly higher (p < 0.05) than in maternal circulation. Galanin
      concentration in amniotic fluid (20.4 +/- 1.0 pg/ml) was similar to that observed
      in maternal plasma, but significantly (p < 0.01) lower than in umbilical cord
      blood. A significant correlation was found between maternal body mass index and
      plasma galanin concentration (tau = 0.246; p < 0.05) and between birth weight and
      cord blood galanin concentration (tau = 0.345; p = 0.01). There was no
      significant correlation between placental mass and cord blood galanin
      concentration (tau = 0.124; p = 0.26). CONCLUSIONS: Plasma galanin concentration
      in pregnant women before term delivery is similar to that in non-pregnant women.
      The fetus rather than the placenta is the source of the high galanin
      concentration in umbilical cord blood. The role of galanin in the regulation of
      newborn weight is uncertain.

PMID- 17558690
TI  - Serum levels of interleukin-6, interleukin-1beta and human chorionic gonadotropin
      in pre-eclamptic and normal pregnancy.
AB  - Studies in placentas from the first trimester and in vitro models indicate that
      interleukin (IL)-1beta and IL-6 induce the release of human chorionic
      gonadotropin (hCG). During pre-eclampsia there is an increase of pro-inflammatory
      cytokines; however, its relationship with hCG levels during the third trimester
      of pregnancy has not been determined. The aim of the present study was to
      evaluate the relationship between blood levels of IL-6, IL-1beta and hCG in
      normal pregnancy and pre-eclampsia. Blood samples during the third trimester of
      pregnancy from women with severe pre-eclampsia (n = 20) or normal pregnancy (n =
      20) were assayed for hCG by immunoassay, IL-6 and IL-1beta by enzyme-linked
      immunosorbent assay. Serum level of IL-6 was significantly higher in pre
      eclamptic than in normal women (16.5 +/- 2.1 vs. 4.9 +/- 1.1 pg/ml); however, IL
      1beta was similar in both groups. Although hCG was higher in pre-eclampsia than
      normal pregnancy, the difference was not statistically significant. Furthermore,
      IL-1beta in normal pregnancy was correlated negatively with hCG (r = -0.69, p <
      0.001). In conclusion, serum levels of IL-6 were increased in pre-eclampsia but
      were not correlated with hCG or IL-1beta; however, in normal pregnancy there was
      a negative correlation between IL-1beta and hCG. The interaction between IL-1beta
      and hCG at the third trimester needs to be investigated.

PMID- 17558693
TI  - Haemopoietic stem cell transplantation--an evolving treatment for severe
      autoimmune and inflammatory diseases in rheumatology, neurology and
      gastroenterology.
AB  - The concept of haemopoietic stem cell transplantation (HSCT) to treat severe
      autoimmune diseases has been around for several decades. Advances in the safety
      of HSCT have made it a clinical reality since 1995. Databases have registered
      around a thousand patients treated specifically for a wide range of diseases,
      predominantly multiple sclerosis (MS), systemic sclerosis (SSc), rheumatoid
      arthritis (RA) and systemic lupus erythematosus (SLE). Phase I/II prospective and
      retrospective studies have supported the potential of autologous HSCT as a
      treatment option in severely affected patients, with profound and prolonged
      clinical responses in some diseases, although procedures are generally not
      curative. Allogeneic HSCT appears to offer curative potential, but the potential
      of high toxicity has limited its use in this context. The exact role of HSCT
      remains to be defined, particularly in the context of other advances in the
      treatment of autoimmune disease. Along with other groups, the European Group for
      Blood and Marrow Transplantation (EBMT) are overseeing several phase III trials
      in autologous transplantation. Given the risks of the HSCT, eligibility is
      restricted to patients who have severe, treatment resistant disease, in whom the
      prognosis is otherwise poor. This review aims to summarise the current published
      data in this evolving treatment for relatively rare patients with resistant or
      rapidly progressive disease where treatment options are otherwise limited. This
      cross-fertilization of knowledge between many specialties may provide increasing
      therapeutic opportunities in otherwise untreatable diseases. Moreover, destroying
      and rebuilding immune systems may provide insights into autoimmune diseases.

PMID- 17558694
TI  - Non-myeloablative hematopoietic stem cell transplantation is of limited value in
      advanced or refractory acute myeloblastic leukemia. The Mexican experience.
AB  - Allogeneic hematopoietic stem cell transplantation (HSCT) is an effective
      strategy for preventing relapse of acute myelogenous leukemia (AML). We analyzed
      the outcome of 31 primary AML patients who received a reduced-intensity
      conditioning regimen for allogeneic HSCT in first or second remission. Thirty-one
      AML patients, 20 in first complete remission (FCR), 8 in second complete
      remission (SCR) and 3 in a partial remission (SPR) were included. All received
      busulfan 4 mg/kg/d/2 days, fludarabine 30 mg/m(2)/d/3 days and cyclophosphamide
      350 mg/m(2)/d/3 days as conditioning regimen. The median number of CD34+ cells
      infused was 5.6 x 10(6)/kg and 5.2 x 10(6) in FCR and SCR group, respectively.
      All patients received cyclosporine-A (CsA) and methotrexate as graft vs. host
      disease (GvHD) prophylaxis. All patients showed myeloid engraftment (neutrophils
      >0.5 x 10(9)/l) after a median of 13 days in FCR group and 15 days in SCR group.
      Platelet recovery >20 x 10(9)/l was achieved after a median of 13 days in both
      groups. Relapse for 20 patients in FCR was 35% compared to 91% for 11 in SCR/SPR
      (p < 0.05). Conclusions. Reduced-intensity conditioning followed by allogeneic
      HSCT can induce stable remission in primary AML patients transplanted in FCR. A
      high relapse rate was documented in patients with refractory or relapsed AML.

PMID- 17558695
TI  - Circulating T cells in patients with untreated acute myelogenous leukemia are
      heterogeneous and can be activated through the CD3/TCR complex.
AB  - T lymphocyte defects may contribute to the immune insufficiency seen in acute
      myelogenous leukemia (AML). We therefore characterized the T cell system for
      untreated AML patients. T lymphocyte subsets were analyzed by flow cytometry for
      45 AML patients. The in vitro interferon-gamma (IFNgamma) release in response to
      stimulation with anti-CD3 plus anti-CD28 in the presence of autologous AML cells
      was examined for 31 patients. The majority of circulating lymphocytes were
      CD3(+)T cells, and CD19(+)B cells usually constituted < 10% of the lymphocytes.
      Most T cells expressed the alphabeta T cell receptor (TCRalphabeta(+)), and only
      a minority of the cells was TCRgammadelta(+). Both CD4(+) and CD8(+)T cells were
      detected, the CD4:CD8 ratio showed a wide variation but was generally >1.0. The
      majority of CD4(+) and CD8(+)T cells were CD45RA(+) cells. The T cells could be
      stimulated to release IFNgamma in response to anti-CD3 plus anti-CD28 ligation
      even in the presence of excess autologous AML blasts, and for a subset of
      patients (6 of 27) these IFNgamma levels could be further increased by the novel
      protein kinase C (PKC) agonist PEP005. In conclusion, circulating T cells in
      patients with untreated AML are mainly CD4(+) or CD8(+) TCRalphabeta(+); both
      CD45RA(+) and CD45R0(+) can be detected, and these cells can be activated through
      the CD3/TCR complex even in the presence of excess AML cells. For a subset of
      patients T cell responsiveness can be further increased by targeting PKC and
      these data therefore suggest that T cell function is not inhibited in AML
      patients.

PMID- 17558696
TI  - Markers of apoptosis and proliferation related gene products as predictors of
      treatment outcome in childhood acute lymphoblastic leukemia.
AB  - The aim of the study is to characterize markers of apoptosis in children with
      acute lymphoblastic leukemia (ALL) in relation to treatment outcome of the
      disease. The study was performed on 34 children with ALL and 39 healthy children
      as a control group. Apoptosis was assessed by cell morphology; DNA fragmentation;
      ELISA and RT-PCR for CD95, CD95L, BcL-2 and nuclear factor-kappa B (NF-kappaB);
      and flow cytometry for CD95, CD40, CD49d and CD11a. Apoptosis was significantly
      lower in patients than controls. Apoptosis detected by CD95 ligand was
      significantly lower in cases with no remission after treatment than those who
      achieved remission. Anti-apoptotic factors: CD40, BcL-2, and NF-kappaB were all
      found to be higher in cases than controls and in cases with no remission than
      those achieved remission. CD49d was significantly lower in cases than controls,
      and significantly lower in cases with who did not achieve remission. CD11a levels
      were similar in the various groups. Delayed apoptosis of ALL cells is genetically
      controlled either directly or indirectly by a network of oncogenes and tumor
      suppressor genes. CD40 appeared to stimulate both T and B lineage and is
      considered the most potent influencer and predictor of resistance to therapy.
      Inhibitors for the activity of CD40, Bcl-2 and NF-kappaB as well as stimulants to
      CD95 could have a potential therapeutic benefit.

PMID- 17558697
TI  - Troxacitabine in acute leukemia.
AB  - Troxacitabine (Troxatyl; BCH-4556; (-)-2'-deoxy-3'-oxacytadine) is the first
      synthetic l-nucleoside enantiomer to demonstrate broad spectrum cytotoxic
      activity. It was obtained by exchanging the sulphur endocyclic atom with oxygen
      in the structure of lamivudine, following the discovery that this agent had
      cytotoxic, as well as anti-viral activity. The unique "unnatural" stereochemistry
      of troxacitabine has produced impressive cytotoxic potency against a wide range
      of malignancies in the laboratory which led to its selection for clinical
      development. The initial trials with troxacitabine have established its efficacy
      in both solid and haematological malignancies, including those resistant to ara-C
      (cytarabine). This review will consider troxacitabine in terms of its
      pharmacology, mode of action, pharmacokinetics, tolerability and clinical
      efficacy.

PMID- 17558698
TI  - Chronic lymphocytic leukemia in India--a clinico-hematological profile.
AB  - Chronic lymphocytic leukemia (CLL) is the most common form of leukemia in elderly
      people. The clinico-hematological profile and treatment outcome of patients with
      CLL were assessed using retrospective case record analysis over 11 years. There
      were 95 (75 males: 20 females) patients with a median age of 61 years. Thirty
      patients were aged 55 years or less (young CLL patients) and 65 were more than 55
      years of age (elder CLL patients). Sixty percent patients had non-specific
      complaints, such as weakness, cough and indigestion. Twenty-six (27%) patients
      had pallor and 24 (25%) had fever as initial presenting manifestation. Bleeding
      manifestations were seen in 7 patients. Seven patients were diagnosed
      incidentally. Lymphadenopathy, splenomegaly and hepatomegaly were seen in 52
      (55%), 63 (66%) and 60 (63%) patients, respectively. The median white blood cell
      count and absolute lymphocyte counts were 70,600 and 51,490/mul, respectively.
      Three patients had autoimmune hemolytic anemia. Twenty-five patients (26%) had
      anemia with hemoglobin < 11 g/dl and thrombocytopenia with platelet count 100 x
      10(3)/mm(3) was seen in 17 (18%). Interstitial nodular, mixed and diffuse bone
      marrow (BM) involvement was seen in 10.2, 67.3, 6.1 and 16.3% cases,
      respectively. Eighteen (60%) young patients and 35 (54%) older patients required
      treatment with chlorambucil. The mean time from initial diagnosis to treatment
      was 4.6 +/- 10.7 months. None of our patient attained complete response. Six
      patients obtained partial response. Median duration of chlorambucil was 7 months
      (1-86 months). Forty-six patients had stable disease. Three patients died. Median
      survival of study group was 4 years (8 months-13 years). In older CLL it was 4
      years (8 months-11 years) and in young patients, survival duration was 5.5 years
      (1-13 years).

PMID- 17558699
TI  - Bortezomib in combination with thalidomide-dexamethasone for previously untreated
      multiple myeloma.
AB  - In a previous trial among 137 previously untreated patients with multiple
      myeloma, the combination of thalidomide-dexamethasone induced remission in 66% of
      patients, including complete remission in 13%. In an attempt to induce more
      frequent remissions, we added bortezomib to this program. Between 7/03 and 3/06,
      38 newly diagnosed patients with multiple myeloma received at least one, but no
      more than 3, courses of bortezomib in a dose of 1.3 mg/m(2) IV x 4; dexamethasone
      20 mg/m(2) PO for 4 days beginning on days 1, 9, 17; thalidomide 100 mg PO daily
      increasing to a maximum of 200 mg. There was rapid onset of remission in 33
      patients (87%) including 6 patients with complete remission (16%). Most side
      effects were preventable, but otherwise were usually mild and reversible. After a
      median of 4 months, 25 eligible patients received intensive therapy with high
      dose melphalan supported by autologous blood stem cells, so that the myeloma was
      in complete remission in 14 patients (37% of all patients). The combination of
      bortezomib-thalidomide-dexamethasone was a highly effective primary treatment for
      newly diagnosed patients with multiple myeloma.

PMID- 17558700
TI  - CMED in the treatment of nasal natural killer cell lymphoma with distant
      metastases.
AB  - INTRODUCTION: Nasal natural killer (NK) cell lymphoma that showed distant
      metastases generally showed an poor prognosis. We described a group of patients
      with these atypical presentation and that were treated with an intensive, short
      chemotherapy/radiotherapy regimen. METHODS: Sixty-one patients fulfilled the
      criteria for NK cell lymphoma with distant metastases and all have very poor
      prognostic factors: high clinical risk, multiple extranodal presentation and
      bulky disease (tumor mass >10 cm). They were treated with CMED (cyclophosphamide
      2000 mg/m(2), iv, day 1, methotrexate 400 mg/m(2), iv, day 1(with leucovorin
      rescue), etoposide 400 mg/m(2) twice and dexametasone 40 mg daily for 4 days). If
      complete response (CR) was observed, they were received adjuvant radiotherapy (50
      Gy) to nasal region. Patients with failure were treated with different salvage
      treatments. RESULTS: Forty nine patients achieved CR and 12 were considered
      failure, all patients that were failure and nine that relapse die secondary to
      tumor progression. Median follow-up were 46 months (range 34-68 months). Median
      has not been observed in relapse-free survival (RFS) and overall survival (OS).
      Actuarial curves at 5 years showed that RFS was 81% and OS was 65%. Treatment was
      well tolerated. CONCLUSIONS: Nasal NK cell lymphoma with distant metastases is
      considered an rare clinical entity, probably is under diagnosis because it has
      been included as stage III and IV in previous reports, that showed an very poor
      RFS and OS. The treatment herein report could achieve good response and outcome,
      but it is evident that more specific and aggressive therapy is necessary in these
      setting of patients.

PMID- 17558701
TI  - Thirty-nine cases of pure red cell aplasia: a single center experience from
      India.
AB  - Pure red cell aplasia (PRCA) is an uncommon disorder, characterized by
      transfusion dependent anemia, reticulocytopenia with selective aplasia or paucity
      of erythroid cells in bone marrow. There are only a few large series of PRCA
      reported in literature. This is the largest single center series of PRCA from
      India. OBJECTIVE: To evaluate the utility of Immunohistochemistry with
      Glycophorin A on bone marrow biopsies in quantitating the cut-off percentage of
      erythroid blasts required for diagnosis, as the upper cut-off percentage of
      erythroblasts for establishing a diagnosis of PRCA is still not clear. METHODS:
      The clinical data were obtained from patients' case files. Immunohistochemistry
      with Glycophorin A was performed using an immunoperoxidase technique and
      percentage of Glycophorin A positive cells of all nucleated cells was calculated
      by two independent observers. RESULTS: In our study, bone marrow aspirates showed
      a variable percentage of erythroblasts ranging from 2 to 12% (mean 6.3%) in
      children and from 1 to 8% (mean 4.6%) in adults on Giemsa smears.
      Immunohistochemistry (IHC) with Glycophorin A showed a mean positive cell % of
      8.2 (range 2-16%) and 6.8 (1-9%) in pediatric and adult respectively against a
      mean of 28% (range 21-39%) in idiopathic thrombocytopenia (ITP) cases. Treatment
      with prednisone showed good response in a majority of both adults and childhood
      PRCA. Cyclosporine was found to be a good alternative in prednisone non
      responders. Thymectomy was beneficial in patients with thymoma. CONCLUSION: A
      higher percentage of erythroid cells (>5%) does not exclude a diagnosis of PRCA
      in an appropriate clinical setting and therefore can be managed as PRCA.

PMID- 17558702
TI  - Iron deficiency anaemia and evaluation of the utility of iron deficiency
      indicators among healthy Nigerian children.
AB  - The hemoglobin (Hb), serum iron (SI), total iron binding capacity (TIBC),
      transferrin saturation (TS) and serum ferritin (SF) values of 240 apparently
      healthy children were determined in a prospective cross-sectional study conducted
      in Port Harcourt, Nigeria. Standard colorimetric and enzyme immunoassay
      procedures were used for the estimation all variables. The mean values of all
      parameters in this study population were; Hb (11.2 +/- 1.83 gldl), TIBC (361.4 +/
      245.7 ugldl, log(c) SI (1.807 +/- 0.45), log(c) SF (1.51 +/- 0.47) and TS (29.3
      +/- 18.5%). There was an age-dependent statistical significant difference in the
      Hb, TIBC and TS values (P < 0.01). Sex was not found to exert any significant
      influence on the parameters except TIBC. TS had the highest sensitivity and
      efficiency values of 48 and 95%, respectively. Positive predictive value (PPV),
      likelihood ratio (LR(+)) and post-test probability values were highest with SF
      (58%, 3.3 and 62.2%, respectively) as a diagnostic indicator. Hb values
      correlated positively and significantly with TS (P < 0.01), log(c) SI and log(c)
      SF concentrations (P < 0.05). Log(c) SF also correlated positively and
      significantly with Hb and TIBC (P < 0.05). The overall prevalence of iron
      deficiency anaemia among these children was 33.75%. We conclude that there is a
      high prevalence of iron deficiency anaemia among apparently healthy children
      under the age of five years in this part of the world and these results may
      justify the need for the introduction of a broad intervention programme for this
      highly vulnerable group. This study is also in support of the hypothesis that SF
      is the best test for diagnosing or excluding iron deficiency anaemia. The
      combination of SF, Hb and TS determinations may prove more useful in a resource
      limited moderate setting.

PMID- 17558703
TI  - Ineffectiveness of oral iron hydroxide polymaltose in iron-deficiency anemia.
AB  - Two hundred and forty one patients with iron deficiency anemia (IDA) were
      identified in a single institution over a 24-year period; of these, 75
      individuals were studied as the result of persistent IDA despite the
      administration of oral iron hydroxide polymatose (IP). The levels of hemoglobin
      when the patients were referred for study after being given oral IP had a median
      of 10.3 g/dl; after administration of oral iron fumarate during periods ranging
      from 1 to 14 months, the levels of hemoglobin rose to a median of 12.5 g/dl
      (p>0.01). Our data support previous observations made in other countries about
      the ineffectiveness of oral IP in the treatment of individuals with IDA and
      should alert the clinician to avoid unnecessary consultations and misdiagnosis.

PMID- 17558704
TI  - Hematological presentation in systemic lupus erythematosus and its relationship
      with disease activity.
AB  - Abnormalities of hematological system are very common in systemic lupus
      erythematosus (SLE). The aim of the study is to evaluate hematological findings
      in patients with SLE at the time of referral and their relationship with disease
      activity and organ involvement. The study was carried consecutive 115 patients,
      including 20 males and 85 females. Most of the cases had anemia at the time of
      presentation due to various etiologies. Anemia of chronic disease was seen in 46%
      and it was the most common encountered picture. The rate of hemolytic anemia was
      28%, and Coombs' positivity rate was 22% among our patients. Leukopenia ( < 4.0 x
      10(9)/l), neutropenia ( < 1.8 x 10(9)/l), and lymphopenia ( < 1.5 x 10(9)/l)
      rates were 57, 20, and 82%, respectively. Thrombocytopenia was seen in 40% for <
      150 x 10(9)/l, 26% for < 100 x 10(9)/l, and 8% for < 50 x 10(9)/l. Of our
      patients, 10% had antiphospholipid syndrome (APS) at the time of diagnosis.
      Increased fibrinogen levels were observed in 35% without relating to disease
      activity. The rates of C3 and C4 hypocomplementemia were 86 and 64%,
      respectively, and both are closely correlated with the disease activity.
      Moreover, C3 hypocomplementemia was more prominent in cases with renal or serosal
      involvement. Leukopenia and hyperfibrinogenemia were more common in patients with
      skin/mucosal involvements. C3 hypocomplementemia, APS and elevated IgG levels
      were more common in our patients with renal involvement. SLE should be kept in
      mind while evaluating patients with mentioned hematological findings, especially
      in those with accompanying organ involvements.

PMID- 17558705
TI  - All-trans retinoic acid attacks reverse transcriptase resulting in inhibition of
      HIV-1 replication.
AB  - We previously reported that all-trans retinoic acid (ATRA) inhibited growth in
      HTLV-1-positive T-cell lines and fresh cells from patients with adult T-cell
      leukemia. Interestingly, ATRA significantly inhibited reverse transcriptase (RT)
      activity similar to azidothimidine (AZT) in HTLV-1-positive T-cell lines. To
      clarify whether ATRA has an inhibitory effect on the replication of HIV, we
      examined HIV proviral DNA in a HIV-1-positive cell line (8E5) using real time
      PCR. ATRA as well as AZT reduced the proviral DNA load of 8E5 in a dose-dependent
      manner. These results suggest that there is a common element of ATRA signaling in
      both HTLV-1 and HIV. Furthermore, we examined the effects of ATRA on viral
      replication in primary lymphocytes of three individuals infected with HIV. ATRA
      reduced viral replication significantly similar to AZT. These findings suggested
      that ATRA acts as a RT inhibitor, reducing the HIV-1 proviral DNA load. Finally,
      we conclude that ATRA may be a potential therapeutic agent for HIV infection.

PMID- 17558706
TI  - Effect of gamma irradiation on blood from glucose 6 phosphate dehydrogenase
      deficient blood donors.
AB  - Recently, the irradiation of cellular blood components has received increased
      attention. Normal red blood cells (RBC) when subjected to gamma irradiation show
      increase in haemolysis and increased storage lesions. Glucose 6 phosphate
      dehydrogenase (G6PD) deficient blood is lacking in anti-oxidant properties which
      protect the RBC membrane and therefore when subjected to gamma irradiation, it
      may lead to increased haemolysis. In this study, 500 healthy non-remunerated
      blood donors were screened for G6PD deficiency. About 350 ml of whole blood was
      collected from 10 G6PD deficient donors (cases) and 10 units were collected from
      donors who were not deficient for G6PD (controls). All units were subjected to
      gamma irradiation of 25 Gy by a self contained gamma cell irradiator (Nordion
      Canada) on day 0 and then stored at 4 degrees C. Sampling was done from these
      cases and controls on day 0, 7, 14 and 21. Estimation of free plasma hemoglobin
      (Hb), free plasma potassium (K) and lactate dehydrogenase (LDH) was performed. It
      was found that there were no significant changes between the cases and controls
      in any of the parameters assessed, although the values for all the parameters
      were higher in case group at the end of storage period, these differences were
      not statistically significant.

PMID- 17558707
TI  - A 14-mer peptide from HSP70 protein is the critical epitope which enhances NK
      activity against tumor cells in vivo.
AB  - Heat shock protein 70 (Hsp70) has been found to play key roles in tumor immunity
      due its chaperone function of binding antigenic peptides. Here we report it can
      also stimulate NK cells in vivo, which is another role in Hsp70s' anti-tumor
      response. Injecting Hsp70 into mice increased splenic NK cell populations, which
      may be reason for anti-tumor effect of Hsp70. The Hsp70 14-mer peptide (aa450
      463, TRD) was identified as the critical epitope for this stimulatory activity.
      It was the murine Hsp70 14-mer peptide TRD instead of the corresponding human
      Hsp70 14-mer peptide TKD that functioned in the mouse experimental model.

PMID- 17558708
TI  - Serum CD40/CD40L system in Graves' disease and Hashimoto's thyroiditis related to
      soluble Fas, FasL and humoral markers of autoimmune response.
AB  - Activated CD4 T cells' express CD40 ligand (CD154) interacting with CD40 on the B
      cells surface, protecting them from Fas-mediated apoptosis and in this study,
      influence humoral response. The aim of the study was to assess soluble CD40 and
      CD154 in Graves' disease (GD) and Hashimoto's thyroiditis (HT) in relation to Fas
      and FasL and to the markers of humoral response: aTPO, aTG and aTSHR. The study
      was carried out in 5 groups of subjects: 1/14 patients with GD in euthyreosis on
      methimazol (euGD), 2/20 patients with hyperthyroid GD (hrGD), 3/15 patients with
      HT in euthyreosis on levothyroxine (euHT), 4/16 patients with hypothyroid Ht
      (hoHT), 5/12 healthy volunteers, age and sex-matched to groups 1-4. The serum
      levels of CD40, CD154, Fas and FasL, aTPO and aTG were determined by ELISA and
      aTSHR was determined by the RIA method. CD40 serum concentration was
      significantly higher in hoHT individuals: 55.8 (24.0-83.2) pg/ml (p<0.01) and
      euHT patients: 51.2 (20.0-80.1) (p<0.05) as compared to the controls. Also sCD40L
      values were significantly increased in euHT individuals: 5.1 (1.0-11.8) (p<0.05)
      and hoHT patients: 3.9 (0.7-11.2) ng/ml (p<0.05) as compared to the controls.
      There was a positive correlation between sCD40 and sCD154 in the patients studied
      (r=0.36, p<0.001). In HT patients we found positive correlations between sCD40
      and aTPO (r=0.45, p<0.001) and sFas (r=0.36, p<0.05) as well as a negative
      correlation between sCD40 and FasL (r=-0.24, p<0.05). In GD patients there was a
      positive correlation between sCD40 and aTSHR (r=0.28, p<0.05). In summary, our
      results suggest that CD40/CD154 interaction plays an important role in the
      regulation of autoimmune humoral response, both in Hashimoto's thyroiditis and
      Graves' disease. Fas-mediated apoptosis seems to be involved in this process
      especially in Hashimoto thyroiditis. Soluble CD40 may serve as a marker of the
      active stage of autoimmune thyroid disease.

PMID- 17558709
TI  - No evidence of association of CTLA-4 -318 C/T, 159 C/T, 3' STR and SUMO4 163 AG
      polymorphism with autoimmune diabetes.
AB  - Autoimmune diabetes is an organ specific and multifactorial disorder including
      insulin dependent diabetes mellitus (Type 1 Diabetes) and latent autoimmune
      diabetes in adults (LADA), which progresses to insulin dependency because of the
      beta cells destruction. Several polymorphisms in different genes have been
      associated with diabetes. The CTLA4 gene is considered a down regulator of T cell
      function, and the SUMO4 gene encodes a small ubiquitin-like modifier implicated
      in the intensity and duration of the immune response. We selected 62 LADA
      patients, 123 patients with Type 1 diabetes patients and 136 unrelated volunteers
      to study CTLA4 -318 C/T, 159 C/T, 3' STR and SUMO4 163 A/G polymorphisms by PCR.
      There was a statistical difference significant in the frequency of the allele
      209pb for the 3'STR between LADA and Type 1 diabetes patients but not with
      respect the normal group, the frequencies were found to be 6.9%, 1.0% and 1.9%,
      respectively. However, no association with either of the polymorphisms has been
      found in the studied population. The knowledge of the several susceptibility loci
      in autoimmune diabetes will enhanced the prediction of individuals at high risk
      of developing the disease in order to establish the best treatment and the
      prevention of autoimmune diabetes.

PMID- 17558710
TI  - MHC-restricted presentation of a single repeat of MUC1 mucin.
AB  - Major histocompatibility complex (MHC) restriction of antigen presentation of a
      single mucin1 (MUC1) variable number of tandem repeats peptide (VNTR1) was
      examined by generating cytotoxic T lymphocytes (CTL) derived from peripheral
      blood mononuclear cells (PBMC) stimulated with a single repeat MUC1 peptide
      presented by allogeneic (MHC-independent) or autologous (MHC-dependent) Epstein
      Barr Virus (EBV) immortalized B lymphocytes. The ability to generate greater CTL
      activity against MUC1-expressing tumor cells by stimulation with autologous
      versus allogeneic EBV-B supports the hypothesis that presentation of a single
      repeat of MUC1 peptide is MHC-restricted (MHC-dependent).

PMID- 17558711
TI  - Relations between serum IgA level and cartilage erosion in 436 cases of
      rheumatoid arthritis.
AB  - The objective of this work was to explore the correlation between the cartilage
      erosion tested with X-ray image and the serum immune globulin level in rheumatoid
      arthritis (RA). Four hundred and thirty-six patients with active RA in
      preliminary diagnosis were selected for the study. The cartilage erosion was
      measured by X ray in both hands as a grade index, and IgG, IgM as well as IgA in
      serum were determined with immunoturbidimetry. The correlation between the X-ray
      grading and serum immune globulin outcomes was analyzed by SPSS13.0 statistic
      package. RESULT: More patients with X-ray grading as cartilage erosion (slight,
      medium or severe) showed abnormal IgA comparing to those in X-ray grading as
      normal (p<0.05-0.01) both in preliminary investigation and after 6 months' follow
      up. The serum IgA level in RA with X-ray grading as slight, medium or severe
      cartilage erosion was elevated remarkably comparing with in grading as normal
      (p<0.05-0.01). The Spearman Analysis showed that the level of serum IgA presents
      positive correlation with X-ray grading both in preliminary investigation
      (p=0.003, rIgA=0.143) and after 6 months follow-up (p=0.001, rIgA=0.173). IgG and
      IgM, however, have no correlation with X-ray image outcomes. The increase of
      serum IgA shows positive correlation with the grade of cartilage damage in active
      RA. IgA seems to be involved in the mechanism of joint cartilage erosion in
      active RA.

PMID- 17558712
TI  - Vanadate-induced inhibition of BCR-triggered apoptosis is coupled with tyrosine
      phosphorylation and induction of G2M growth arrest in Ramos-BL B cells.
AB  - The regulation of the tyrosine phosphorylation of key signaling molecules by
      tyrosine kinases and phosphatases is essential for BCR-triggered signaling
      cascades during B cell selection process. We used the non-selective tyrosine
      phosphatase inhibitor vanadate to study the importance of the late regulation of
      the tyrosine phosphorylation for BCR-triggered G1 growth arrest and apoptosis in
      Ramos-BL B cells. Vanadate induces G2M growth arrest in a dose-dependent manner
      and prevents BCR-triggered apoptosis. Vanadate-induced upregulation of the
      tyrosine phosphorylation is concomitant with increased expression of cyclin B and
      inhibition of caspase-3 activation and PARP cleavage. The anti-apoptotic effect
      of vanadate was observed even when added up to 6 hours after the treatment of
      Ramos-BL B cells with anti-IgM. Vanadate increases BCR-triggered tyrosine
      phosphorylation of the cytosolic tyrosine phosphatases, SHP-1 and SHP-2 after 24
      hours. Co-stimulation with anti-CD40 prevents anti-IgM-triggered tyrosine
      phosphorylation of these phosphatases and up-regulates the expression of SHP-1.
      We conclude that the regulation of the tyrosine phosphatase activity is
      indispensable for BCR-triggered execution of the apoptosis in Ramos-BL B cells.

PMID- 17558713
TI  - Frequency of carriers of 8.1 ancestral haplotype and its fragments in two
      Caucasian populations.
AB  - Within the human MHC region larger stretches of conserved DNA, called conserved
      ancestral haplotypes exist. However, many MHC haplotypes contain only fragments
      of an ancestral haplotype. Little is known, however, on relative distribution of
      the ancestral haplotypes to their fragments. Therefore we determined the
      frequency of carriers of the whole ancestral haplotype 8.1 (AH8.1) and its
      fragments in 127 healthy Hungarian people, 101 healthy Ohioian females, and in
      nine Hungarian families. The HLA-DQ2, HLA-DR3(17), RAGE -429C allele, the mono-S
      C4B genotype, the HSP70-2 1267G allele and the TNF -308A (TNF2) allele were used
      as markers of the AH8.1. Frequency of carriers of the whole AH8.1 and its
      fragments was similar in the both populations. 18% of the subjects carried the
      whole AH8.1 in at least one chromosome, while 17-20%, 36-39%, and 24-29%,
      respectively carried two or three constituents of the haplotype, only one
      constituent or none of them. Similar results were obtained in the family study.
      In addition, marked differences were found in the relationship of the
      constituents' alleles to the whole AH8.1. In both populations, 29%, 50-59%, 52
      56% and 76-96%, respectively of the carriers of HSP70-2 1267G, RAGE-429C, TNF2,
      and mono-S carriers carried the whole 8.1 haplotype. These findings may have
      important implications for studies of the disease associations with different MHC
      ancestral haplotypes.

PMID- 17558714
TI  - Naive and memory CD4+ T-cells in the cerebrospinal fluid of children with aseptic
      meningitis following measles-mumps-rubella vaccination and enteroviral
      meningitis.
AB  - We investigated the distribution of memory (CD45RO+) and naive (CD45RA+CD62L+)
      CD4+ T-cells as well as CD8+ T-cells and total T-cells in the CSF of children
      with aseptic meningitis following measles-mumps-rubella (MMW) vaccination and
      those with enteroviral meningitis. Flow cytometric analysis of CSF cells was
      performed in 12 children with MMR vaccine-associated meningitis and 11 children
      with enteroviral meningitis. Percentages of total T-cells, CD4+ and CD8+ T-cells
      and monocytes in CSF of patients from the two groups were not significantly
      different. The majority of CD4+ T-cells in the CSF of both patient groups were of
      memory phenotype. Percentages of CSF naive CD4+ T-cells were increased in
      children with aseptic meningitis following MMR vaccination. Further studies
      focused on the more detailed immunophenotyping of CSF cells are needed to fully
      establish the usefulness of flow cytometry in the diagnostic workup of
      inflammatory CNS diseases in children.

PMID- 17558715
TI  - Neutrophils induce the maturation of immature dendritic cells: a regulatory role
      of neutrophils in adaptive immune responses.
AB  - Th1-type immune cytokines are essential to establish adaptive immunity against
      various microbial pathogens, including Escherichia coli, which cause most urinary
      tract infections (UTIs). Dendritic cells (DCs) are vital to initiate Th1
      immunity, while neutrophils, also referred to here as polymorphonuclear
      leukocytes (PMN) are reported to be involved in Th1 immunity initiation by
      secreting several chemokines and cytokines. We found that lipopolysaccharide
      (LPS)-triggered PMN (LPS-PMN) in vitro induced strong up-regulation of DCs
      surface markers CD40, CD80, MHC-II (Iab), and CD86 either by secreting soluble
      factors, such as TNF-alpha, or by PMN-DC cellular contact. LPS-PMN also
      stimulated DCs to produce IL-12 and TNF-alpha. Furthermore, purified DCs
      activated by LPS-PMN were able to present specific antigen to T cells and drive
      Th1 differentiation by producing large amount of IFN-gamma but low amount of IL
      4. Our results suggest a regulatory role of PMN for DCs function in adaptive
      immune responses, thereby providing a link between innate and adaptive immunity.

PMID- 17558717
TI  - The efficacy of hypnotherapy in the treatment of psychosomatic disorders: meta
      analytical evidence.
AB  - Hypnotherapy is claimed to be effective in treatment of psychosomatic disorders.
      A meta-analysis was conducted with 21 randomized, controlled clinical studies to
      evaluate efficacy of hypnosis in psychosomatic disorders. Studies compared
      patients exclusively treated with hypnotherapy to untreated controls. Studies
      providing adjunctive standard medical care in either treatment condition were
      also admitted. Hypnotherapy was categorized into classic (n = 9), mixed form (n =
      5), and modern (n = 3). Results showed the weighted mean effect size for 21
      studies was d(+) = .61 (p = .0000). ANOVA revealed significant differences
      between classic, mixed, and modern hypnosis. Regression of outcome on treatment
      dose failed to show a significant relationship. Numerical values for correlation
      between suggestibility and outcome were only reported in three studies (mean r =
      .31). The meta-analysis clearly indicates hypnotherapy is highly effective in
      treatment of psychosomatic disorders.

PMID- 17558718
TI  - Hypnotherapy for the management of chronic pain.
AB  - This article reviews controlled prospective trials of hypnosis for the treatment
      of chronic pain. Thirteen studies, excluding studies of headaches, were
      identified that compared outcomes from hypnosis for the treatment of chronic pain
      to either baseline data or a control condition. The findings indicate that
      hypnosis interventions consistently produce significant decreases in pain
      associated with a variety of chronic-pain problems. Also, hypnosis was generally
      found to be more effective than nonhypnotic interventions such as attention,
      physical therapy, and education. Most of the hypnosis interventions for chronic
      pain include instructions in self-hypnosis. However, there is a lack of
      standardization of the hypnotic interventions examined in clinical trials, and
      the number of patients enrolled in the studies has tended to be low and lacking
      long-term follow-up. Implications of the findings for future clinical research
      and applications are discussed.

PMID- 17558719
TI  - Evidenced-based hypnotherapy for the management of sleep disorders.
AB  - There is a plethora of research suggesting that combining cognitive-behavioral
      therapy with hypnosis is effective for a variety of psychological, behavioral,
      and medical disorders. Yet, very little empirical research exists pertaining to
      the use of hypnotherapy as either a single or multitreatment modality for the
      management of sleep disorders. The existing literature is limited to a small
      subset of nonbiologic sleep disorders. The objectives of this paper are: to
      provide a review of the most common sleep disorders, with emphasis on insomnia
      disorders; discuss the cognitive-behavioral approaches to insomnia; and review
      the existing empirical literature on applications of hypnotherapy in the
      treatment of sleep disturbance. The overreaching goal is to educate clinicians on
      how to incorporate sleep therapy with hypnotherapy. There is an immediate need
      for research evaluating the efficacy of hypnotherapy in the management of sleep
      disturbance.

PMID- 17558720
TI  - Hypnosis for acute distress management during medical procedures.
AB  - The use of hypnosis during medical procedures has a long-standing tradition but
      has been struggling for acceptance into the mainstream. In recent years, several
      randomized-controlled trials with sufficient participant numbers have
      demonstrated the efficacy of hypnosis in the perioperative domain. With the
      advancements of minimally invasive high-tech procedures during which the patient
      remains conscious, hypnotic adjuncts have found many applications. This article
      describes the procedural environment as well as pharmacologic and
      nonpharmacologic interventions to reduce distress. Current research findings,
      controversies in the literature, and safety considerations are reviewed.
      Implications for clinical practice and training as well as directions for future
      research are discussed. Obstacles and possible reasons for the slow acceptance of
      nonpharmacologic interventions, mind-body therapies, and patient-centered
      approaches are addressed.

PMID- 17558721
TI  - Efficacy of hypnotherapy in the treatment of eating disorders.
AB  - Research on the efficacy of hypnosis in the treatment of eating disorders has
      produced mixed findings. This is due in part to the interplay between the
      characteristics of people with eating disorders and the phenomena of hypnosis. In
      addition, several authors have noted that methodological limitations in hypnosis
      research often make evaluation of treatment efficacy difficult. Many of the
      studies extant provide insufficient information regarding the specifics of the
      hypnotic intervention(s) to facilitate replication and clinical implementation.
      Therefore, this paper only reviews literature with replicable methodological
      descriptions. It focuses on the three primary disorders of interest to
      clinicians: bulimia nervosa, anorexia nervosa, and obesity. The implications for
      evaluating treatment efficacy are discussed.

PMID- 17558722
TI  - Effectiveness of hypnotherapy with cancer patients' trajectory: emesis, acute
      pain, and analgesia and anxiolysis in procedures.
AB  - Clinical hypnosis in cancer settings provides symptom reduction (pain and
      anxiety) and empowers patients to take an active role in their treatments and
      procedures. The goal of this paper is to systematically and critically review
      evidence on the effectiveness of hypnotherapy for emesis, analgesia, and
      anxiolysis in acute pain, specifically in procedures with an emphasis on the
      period from 1999 to 2006. Further, it aims to provide a theoretical rationale for
      the use of hypnosis with cancer populations in the whole spectrum of
      illness/treatment trajectory in several clinical contexts. Finally, a treatment
      protocol for management of overt anxiety and phobic reactions in the radiotherapy
      suite is presented, with the intent of having such a protocol empirically
      validated in the future.

PMID- 17558723
TI  - Evidence-based clinical hypnosis for obstetrics, labor and delivery, and preterm
      labor.
AB  - This paper reviews the benefits and effectiveness of hypnosis in obstetrics and
      labor and delivery, demonstrating significant reductions in the use of analgesics
      and anesthesia and in shorter Stages 1 and 2 labors. It presents empirical and
      theoretical rationales for use of hypnosis in preterm labor (PTL) and labor and
      delivery at term. The benefits of hypnosis in relation to labor length, pain
      levels, and the enjoyment of labor, as well as its effectiveness in preterm labor
      are noted in randomized controlled trials and in a meta-analysis. Risk factors
      are reported for preterm delivery; hypnosis significantly prolongs pregnancy. Six
      cases are presented of hypnosis stopping PTL a number of times and when indicated
      at term. A case report of successful use of hypnosis in quadruplets is presented
      with some scripts. Suggestions are made for further research.

PMID- 17558724
TI  - Salient findings: hypnotizability as core construct and the clinical utility of
      hypnosis.
AB  - Six papers of special interest to the hypnosis community have recently appeared
      in the general scientific literatures. Three of these papers were published as
      part of the 2006 Cochrane Collaboration on the utility of medical interventions.
      These reviews analyze the research literature on the efficacy of hypnosis for
      treatment of needle-related pain in children, pain management during childbirth,
      and conversion disorder. Hypnosis is the most promising psychological
      intervention studied for needle-related procedural pain and distress in children
      and adolescents; it is effective as an adjunctive analgesic during childbirth;
      and it is of uncertain usefulness in treatment of conversion disorder. A second
      cluster of three studies unambiguously demonstrates the central role of
      hypnotizability as a predictor of responsiveness in laboratory, analogue
      treatment, and medical practice settings. One of these articles may well be the
      most important hypnosis paper in many years.

PMID- 17558725
TI  - Ready-to-eat cereal products as meal replacements for weight loss.
AB  - OBJECTIVE: To test the effectiveness of three commercially available partial meal
      replacement products on weight-loss outcomes. METHODS: In a randomized controlled
      clinical trial, 164 eligible overweight and obese adults (ages 18-65 years; body
      mass index >/=25 kg/m(2)) were randomly assigned to a Control group (CN) or to
      one of three intervention groups, including 'Cereal Substitution plus Nutrient
      Bar' (CB), 'Cereal and Waffle Substitution plus Nutrient Bar' (CWB), and 'Cereal
      Substitution, no Nutrient Bar' (CR). RESULTS: Compared with the CN group, the CB,
      CWB, and CR groups evidenced significantly greater reductions in weight, body
      mass index, waist, hip, and thigh measurements, and the CB and CR groups
      evidenced significantly greater reductions in percentage body fat. Despite strong
      adherence (88%) and retention (80%), the groups did not differ in cardiovascular
      risk profile, mood, or satiety. CONCLUSIONS: A variety of ready-to-eat cereal
      products may be safely and effectively used as meal replacements in weight-loss
      programs.

PMID- 17558726
TI  - Antioxidant and micronutrient potential of common fruits available in the Indian
      subcontinent.
AB  - Considering the scanty information on Indian fruits, 36 commonly consumed fruits
      were assessed for inhibition of thiobarbituric acid reactive substances,
      superoxide scavenging activity and ferrous ion-chelating ability along with
      levels of micronutrients (namely ascorbic acid, beta-carotene, riboflavin,
      thiamine, zinc, copper, iron, manganese, selenium and total polyphenols). Fruits
      exhibited 24-173% variability for the 13 study parameters. Fresh fruits exhibited
      3.5-4 times higher antioxidant capacity than dry fruits. Ascorbic acid was
      highest in gooseberry (445 mg/100 g), and beta-carotene was highest in ripe mango
      1,200 mg/100 g. Selenium levels could supply 0-33% of the recommended dietary
      allowance. There was a strong association between different indices of
      antioxidant capacity (P<0.001), thiobarbituric acid reactive substances with
      selenium levels (P<0.01), and superoxide scavenging activity and ferrous ion
      chelating ability with zinc content (P<0.05). Results emphasize need for the
      antioxidant quality of fruit in addition to the quantity of fruit consumption.

PMID- 17558727
TI  - Physico-chemical characteristics, nutritional quality and shelf-life of pearl
      millet based extrusion cooked supplementary foods.
AB  - The process variables for extrusion cooking of pearl millet were standardized and
      some of the physicochemical characteristics of the millet extrudates and also the
      nutritional qualities of the millet and legume-based extruded supplementary foods
      were determined. The millet grits less than 355 microm in size, equilibrated to
      18+/-1% moisture content, extruded at 150+/-5 degrees C temperature and at 200+/
      10 rpm of the barrel of a twin-screw extruder yielded the extrudates of 1.75+/
      0.21 expansion ratio and 7.5+/-1.5 kg breaking strength. The cold and cooked
      paste viscosity, the melt energy and also the carbohydrate digestibility of the
      extrudates indicated that the products were pre-cooked and were of ready-to-eat
      nature. The millet was blended with grain legumes (30%) and also with defatted
      soy (15%) separately and extruded to prepare ready-to-eat nutritious foods
      suitable as food supplements to children and mothers. The foods based on the
      millet and legumes and also the millet and soy contained 14.7% and 16.0% protein
      with 2.0 and 2.1 protein efficiency ratio values, respectively. The shelf-life of
      the foods was about 6 months in different flexible pouches at ambient storage
      conditions. The study showed that applications of extrusion cooking technology to
      pearl millet have promise for preparation of diversified and value-added food
      products from the millet.

PMID- 17558728
TI  - Glycemic response of rice, wheat and finger millet based diabetic food
      formulations in normoglycemic subjects.
AB  - Food formulations suitable as dietary supplements to diabetic subjects based on
      wheat, decorticated finger millet, popped (aralu) and expanded (puri) rice each
      blended separately with legumes, non-fat dry milk, vegetable oils, spices and a
      few hypoglycemic ingredients were formulated. The formulations contained 13.0
      18.3% protein, 11.3-11.8% fat, 59.9-67.5% starch and 13.2-18.0% dietary fiber. A
      50-g equivalent carbohydrate portion of the foods in the form of thick porridge
      was provided to eight healthy adult subjects and the postprandial blood glucose
      response was determined. The Glycemic Index (GI) values were 55.4+/-9, 93.4+/-7,
      105+/-6 and 109+/-8 for wheat-based, millet-based, aralu-based and puri-based
      formulations. The variations in the GI could be attributed to the nature of
      available as well as non-available (non-starchy polysaccharides) carbohydrates in
      the foods besides the processing undergone by the cereal ingredients. The higher
      GI of rice formulations could be due to the easily digestible nature of starches
      and also their lower dietary fiber contents. The study revealed the suitability
      of wheat-based formulation as a food supplement or as meal replacer in diabetic
      subjects but the unsuitability of rice-based formulations.

PMID- 17558729
TI  - Comparative study of lipid composition of two halotolerant alga, Dunaliella
      bardawil and Dunaliella salina.
AB  - The composition of polar, neutral and glycolipid fractions of two halotolerant
      algae, Dunaliella salina and Dunaliella bardawil, which are exclusively used for
      the production of beta-carotene was determined in modified medium. In D. salina
      the glycolipid fraction accounted to 28%, in comparison with 40% of D. bardawil.
      However, in D. salina the polar lipid was 42% compared with D. bardawil at 24%.
      The glycolipid fraction of D. bardawil was rich in linolenic acid (81%). In both
      the species we could find elongation in the fatty acids from C(16) to C(20) to
      C(22) and the percentage was higher than the earlier reports (>3%). The polar
      lipid fraction was composed of (in descending order) phosphatidyl glycerol,
      phosphatidic acid, phosphatidic ethanolamine, phosphatidyl choline and
      phosphatidyl glycerol and the neutral lipid fraction, which was rich in
      monoglycerides and diglycerides and diacylglycero-trimethylhomoserine.

PMID- 17558730
TI  - Effects of advice on dietary intake and/or physical activity on body composition,
      blood lipids and insulin resistance following a low-fat, sucrose-containing, high
      carbohydrate, energy-restricted diet.
AB  - AIM: To determine the effect of dietary advice in conjunction with advice to
      increase physical activity on the body composition, blood lipid and insulin
      profiles in overweight women. DESIGN: A 12-week randomized controlled
      intervention study. subjects were assigned to one of four groups: (1) no advice,
      (2) low-fat, high-carbohydrate (including sucrose) energy-reduced diet, (3) 60
      min/day brisk walking, and (4) diet and activity advice as previous. SUBJECTS:
      Sixty-nine overweight women (mean age 41 years). MEASUREMENTS: Dietary compliance
      was assessed by 4-day diet diaries. Activity levels were assessed by Caltractrade
      mark accelerator monitors. Anthropometric changes were recorded at baseline, 6
      and 12 weeks. Fasting blood samples measuring glucose, insulin, and blood lipids
      were recorded at baseline and 12 weeks. RESULTS: Group 4 achieved greatest weight
      loss of 4.2 kg and greatest reduction in waist circumference of 6.5 cm. Groups 2
      and 4 decreased the percentage energy from fat by 5.2%. Group 3 increased the
      percentage energy from fat by 4.0%. Group 4 significantly reduced total
      cholesterol by 0.45 mmol/l and low-density lipoprotein-cholesterol by 0.53
      mmol/l. CONCLUSION: A low-fat, high-carbohydrate, sucrose-containing diet
      combined with increased physical exercise resulted in greater health benefits
      than diet or physical activity advice alone.

PMID- 17558731
TI  - Diet quality in Croatian university students: energy, macronutrient and
      micronutrient intakes according to gender.
AB  - The aim of the study was to evaluate diet quality and nutrient intakes in
      Croatian university students, which are missing for the past 15 years, and also
      to report the prevalence of overweight/obesity and underweight. The subjects were
      663 students (average age 22 years), representing 0.6% of all Croatian university
      students. The Quantified Food Frequency Questionnaire, checked for
      reproducibility and validity, was used for dietary assessment. Students on
      average had an adequate number of daily meals and snacks, but consumption of
      breakfast was irregular, particularly for men. The average energy intake was
      130.1% of the dietary reference intake and the protein intake was more than
      double the dietary reference intake in 64.3% students. Dietary fiber, iron (in
      females), calcium, zinc, folate, and vitamins C, A and E intake were below
      recommendations in both genders. Only 3.8% of females and 21.9% of males were
      overweight/obese (body mass index >25 kg/m(2)). Nutrient intakes significantly
      differed according to gender and better macronutrient but not micronutrient
      intakes were observed in females.

PMID- 17558732
TI  - Hyperthermia, cisplatin and radiation trimodality treatment: a promising cancer
      treatment? A review from preclinical studies to clinical application.
AB  - This review discusses available clinical and experimental data and the underlying
      mechanisms involved in trimodality treatment consisting of hyperthermia,
      cisplatin and radiotherapy. The results of phase I/II clinical trials show that
      trimodality treatment is effective and feasible in various cancer types and sites
      with tolerable toxicity. Based on these results, phase III trials have been
      launched to investigate whether significant differences in treatment outcome
      exist between trimodality and standard treatment. In view of the clinical
      interest, it is surprising to find so few preclinical studies on trimodality
      treatment. Although little information is available on the doses of the
      modalities and the treatment sequence resulting in the largest degree of
      synergistic interaction, the results from in vivo and in vitro preclinical
      studies support the use of trimodality treatment for cancer patients. Animal
      studies show an improvement in treatment outcome after trimodality treatment
      compared with mono- and bimodality treatment. Studies in different human tumour
      cell lines show that a synergistic interaction can be obtained between
      hyperthermia, cisplatin and radiation and that this interaction is more likely to
      occur in cell lines which are more sensitive to cisplatin.

PMID- 17558733
TI  - The effects of 41 degrees C hyperthermia on the DNA repair protein, MRE11,
      correlate with radiosensitization in four human tumor cell lines.
AB  - PURPOSE: The goal of this study was to determine if reduced availability of the
      DNA repair protein, MRE11, for the repair of damaged DNA is a basis for thermal
      radiosensitization induced by moderate hyperthermia. To test this hypothesis, we
      measured the total amount of MRE11 DNA repair protein and its heat-induced
      alterations in four human tumor cell lines requiring different heating times at
      41 degrees C to induce measurable radiosensitization. MATERIALS AND METHODS:
      Human colon adenocarcinoma cell lines (NSY42129, HT29 and HCT15) and HeLa cells
      were used as the test system. Cells were irradiated immediately after completion
      of hyperthermia. MRE11 levels in whole cell extract, nuclear extract and
      cytoplasmic extracts were measured by Western blotting. The nuclear and
      cytoplasmic extracts were separated by TX100 solubility. The subcellular
      localization of MRE11 was determined by immunofluorescence staining. RESULTS: The
      results show that for the human tumor cell lines studied, the larger the
      endogenous amount of MRE11 protein per cell, the longer the heating time at 41
      degrees C required for inducing measurable radiosensitization in that cell line.
      Further, the residual nuclear MRE11 protein level, measured in the nuclear
      extract and in the cytoplasmic extract as a function of heating time, both
      correlated with the thermal enhancement ratio (TER). CONCLUSIONS: These
      observations are consistent with the possibility that delocalization of MRE11
      from the nucleus is a critical step in the radiosensitization by moderate
      hyperthermia.

PMID- 17558734
TI  - Enhancement of macrosphelide-induced apoptosis by mild hyperthermia.
AB  - Hyperthermia is a useful adjunct in cancer therapy as it can increase the
      effectiveness and decrease the toxicity of currently available cancer treatments
      such as chemotherapy and radiation. In the present study, we investigated whether
      41 degrees C hyperthermia (mild HT) for 20 min can enhance macrosphelide (MS5)
      induced apoptosis in human lymphoma U937 cells. Our results revealed that,
      compared with MS5 (5 microM) and mild HT alone, the combined treatment exhibited
      significant enhancement in apoptosis at 6 h, which was evaluated by observing
      morphological changes and DNA fragmentation. Marked increase in the reactive
      oxygen species (ROS) generation was observed immediately after the combined
      treatment. Significant increase in Fas externalization, caspase-8 and caspase-3
      activation, and loss of mitochondrial membrane potential (MMP) was found after
      the combined treatment compared with MS5 and mild HT alone. Moreover, this
      combination can also alter the expression of apoptosis-related proteins as
      evident by the cleavage of Bid and down-regulation of Bcl-2 while no change in
      the expression of Bax was observed. Furthermore, an immediate rise in the
      intracellular calcium ion ([Ca(2+)]i) concentration was observed after the
      combined treatment, which continuously increased in a time-dependent manner. In
      addition, mild HT treatment alone also increases [Ca(2+)]i concentration without
      inducing apoptosis. Our data indicate that early increase in ROS generation is
      mainly responsible for the enhancement of apoptosis after the combined treatment.

PMID- 17558735
TI  - Correlation of malignant phenotypes of human tumour cell lines with augmented
      expression of Hsp72 protein measured by laser scanning cytometry.
AB  - Augmented expression of members of the heat shock protein 70 (Hsp70) family are
      frequently observed in various human cancers. In this study, we examined
      applicability of laser scanning cytometer (LSC) to evaluate the level of Hsp72,
      which is the member constitutively expressed and significantly induced after heat
      shock, in human tumour cell lines. The relative nuclear content of Hsp72 measured
      by LSC correlated well with the relative intracellular content determined by
      Western blotting (R = 0.906). Furthermore, there was a close relationship between
      the relative nuclear content of Hsp72 measured by LSC and the colony-forming
      ability in soft agar, one of the malignant characteristics of tumour cells (R =
      0.880). These results indicate that LSC measurement is useful for predicting the
      degree of malignancy of cancer cells, as it is reliable, faster than Western
      blotting and more objective and quantitative than visual measurements.

PMID- 17558736
TI  - The effects of power on-off durations of pulsed ultrasound on the destruction of
      cancer cells.
AB  - PURPOSE: Low-intensity ultrasound irradiation is a potential method for
      suppressing cancer cell proliferation, inducing apoptosis and delivering specific
      cytotoxic genes or drugs into tumors topographically in future cancer therapies.
      However, ultrasound attenuates rapidly in tissue and produces heat. Pulsed
      ultrasound is frequently used to minimize pain and possible thermal damage to the
      surrounding normal tissue during therapy, since it results in smaller temperature
      increases. This study compared three pulsed-ultrasound strategies for destroying
      cancer cells, measuring their induced temperature increases to determine the
      optimal pulsing parameters. MATERIALS AND METHODS: We performed three types of
      experiment, involving ultrasound with (1) a fixed duty cycle of 50% with variable
      on- and off-times, (2) a fixed off-time with variable on-times, and (3) a fixed
      on-time with variable off-times. RESULTS: The results show that for different
      types of cultured cells (HeLa, HT-29, Ca9-22 and fibroblast) exposed to
      ultrasound of the same frequency (1 MHz) and energy, long pulses combined with
      off-times that are 5-10 times longer (on-/-off-times pairs of 5/25, 25/250, or
      250/2500 ms/ms) cause significant cell destruction whilst avoiding temperature
      increases of more than 1.5 degrees C. Furthermore, the correlation between the
      temperature increase and the percentage of surviving cells is low. CONCLUSIONS:
      Pulsed ultrasound with a long on-time and an even longer off-time exerts a high
      cytotoxic effect but a smaller temperature increase compared with non-pulsed
      ultrasound. This indicates that the cytotoxic effects observed in the current
      study were not purely due to the thermal effects of the ultrasound.

PMID- 17558737
TI  - Phantom experimental study on microwave ablation with a water-cooled antenna.
AB  - Microwave ablation therapy using a water-cooled antenna was studied
      experimentally in a phantom. The development of the heating pattern induced by
      the microwave antenna was determined from the thermocouple-measured temperature
      field, and the influence of the cooling water flow within the antenna on
      temperature distribution and heating pattern was investigated. The shape of the
      heating pattern was pear-like, and the enlarging rate of the heating pattern
      decreased with heating time. Because of strong cooling effect, the heating
      pattern in the region with Z < 0 (where Z = 0 represents the position of
      radiator, Z < 0 and Z > 0 represent the backward direction of the antenna with
      cooling water and forward direction without water, respectively) was smaller in
      diameter than that with Z > 0, and the heating pattern with Z < 0 was slightly
      reduced when the velocity of the cooling water increased. The highest ablative
      temperature occurred with Z > 0 decreasing. Finally, the specific absorption rate
      distribution was also determined and investigated analytically. The present
      results can be helpful in clinical ablation therapy practice and will be
      applicable to multiple applicators for surgical planning.

PMID- 17558738
TI  - Radiofrequency ablation with a high-power generator: device efficacy in an in
      vivo porcine liver model.
AB  - PURPOSE: The purpose of this study was to test the feasibility and efficacy of
      using a high-power generator with nondeployable electrodes to create large zones
      of coagulation in an in vivo porcine liver model. METHODS: With approval from our
      institution's research animal care and use committee, 12 female swine (mean
      weight = 55 kg) were anesthetized and received RF ablation at laparotomy. Twenty
      nine ablations were performed in four groups using: (i) a conventional 200-W
      generator and cluster electrode (n = 4), or an experimental prototype 250-W
      generator and (ii) a single, 17-gauge electrode (n = 9), (iii) a cluster
      electrode (n = 8) or (iv) three electrodes spaced 2.0 cm apart in a triangular
      configuration (n = 8). In the three-electrode group, power was applied by
      switching between electrodes using a prototype switching device. All electrodes
      were internally cooled. Ablation zone size, shape and generator data from each
      group were compared using a mixed-linear model with animals modeled as random
      effects. RESULTS: The high-power generator was able to increase significantly the
      zone of coagulation. Mean (+/-SD) ablation diameter was largest in the switched
      group (4.31 +/- 0.7 cm) followed by the cluster (3.98 +/- 0.5 cm) and single
      electrode (3.26 +/- 0.5 cm) groups. Mean diameter in the high-power single
      electrode group was no different than the low-power cluster group (3.25 +/- 0.4
      cm, p = 0.98). Circularity measures were high (>0.75) in all groups. CONCLUSIONS:
      Coupling a high-power generator and switching device is feasible. At higher
      powers, the switching device creates larger zones of ablation than cluster or
      single electrodes. Single-electrode ablations created with the prototype high
      power generator were equivalent to those produced with the cluster electrode at
      conventional lower powers.

PMID- 17558739
TI  - Theoretical comparison of intraluminal heating techniques.
AB  - INTRODUCTION: This study compared simulated temperature distributions of
      intraluminal heating devices, concerning penetration and homogeneity. A hot water
      balloon, a 434-MHz monopole and a 915-MHz dipole antenna, both with incorporated
      cooling, and a 27-MHz applicator were investigated. METHODS: The hot water
      balloon had an inlet temperature of 45 degrees C and a flow rate of 7.85 ml s(
      1). The cooling water and air had a temperature of 41 degrees C and 37 degrees C
      and a flow rate of 5.89 ml s(-1) and 1.8 l s(-1), respectively. A 27-MHz
      applicator consisting of one or two electrode(s) was modelled to demonstrate
      axial steering for inhomogeneous tissue properties. Calculated power
      distributions were scaled to a total power of 10 W in tissue before the
      corresponding temperature distributions were calculated. RESULTS: The hot water
      balloon and the 27-MHz device showed a thermal penetration depth of approximately
      4 and approximately 10 mm, respectively. The penetration depths of the 434- and
      915-MHz applicators were comparable: approximately 10 and approximately 16 mm
      with water and air cooling, respectively. With the 27-MHz applicator, spatial
      steering was applied to minimize temperature gradients along the applicator. The
      434- and 915-MHz antennas have no steering possibilities. The temperature
      distribution of the hot water balloon is not affected by inhomogeneous dielectric
      properties, only slightly by inhomogeneous perfusion. CONCLUSION: A hot water
      balloon is useful for heating tumours with a limited infiltration in tissue,
      while a 27-MHz device has the best potential to realize a homogeneous temperature
      distribution in larger tumours.

PMID- 17558742
TI  - Regulatory CD4(+)CD25(+) T-cells are controlled by multiple pathways at multiple
      levels.
AB  - CD4(+)CD25(+) regulatory T-cells (Treg cells) are an important subset of T-cells
      that functions to negatively control immune responses to self or non-self
      antigens. Depletion of CD4(+)CD25(+) Treg cells leads to the occurrence of
      lymphoproliferative autoimmune diseases in animals and humans. Therefore,
      CD4(+)CD25(+) Treg cells must be tightly regulated in the physiologic situation.
      In this article, we try to summarize the regulating pathways of the development,
      survival, and function of CD4(+)CD25(+) Treg cells at multiple levels and
      multiple pathways, including the dendritic cells, costimulatory signals,
      cytokines, as well as intracellular signals.

PMID- 17558743
TI  - Targeting costimulatory pathways for tumor immunotherapy.
AB  - Tumor immunotherapy harnesses the potential of the host immune system to
      recognize and eradicate neoplastic tissue. The efficiency of the immune system in
      mediating tumor regression depends on the induction of antigen-specific T-cell
      responses through physiologic immune surveillance, priming by vaccination, or
      following adoptive transfer of T-cells. Although a variety of tumor-associated
      antigens have been identified and many immunotherapeutic strategies have been
      tested, objective clinical responses are rare. The reasons for this include the
      inability of current immunotherapy approaches to generate efficient T-cell
      responses, the presence of regulatory cells that inhibit T-cell responses, and
      other tumor escape mechanisms. The activation of effector T-cells depends on
      interactions between the T-cell receptor (TCR) and cognate antigen presented as
      peptides within the major histocompatibility complex (MHC) and costimulatory
      signals delivered by CD28, which binds to B7.1 and B7.2. More recently, several
      new molecular receptors and ligands have been identified that integrate into
      stimulatory or inhibitory activity for T-cells. These signals have been loosely
      associated with the costimulatory molecules but actually represent a diverse
      group of molecular pathways that have unique and overlapping functions. This
      review will focus on these pathways and emphasize their role in mediating T-cell
      activation for the purpose of enhancing tumor immunotherapy. As we gain a better
      understanding of the molecular and cellular consequences of T-cell signaling
      through the costimulatory pathways, a more rational approach to the activation or
      inhibition of T-cell responses can be developed for the treatment of cancer and
      other immune-mediated diseases.

PMID- 17558744
TI  - Advances in immunotherapy of multiple myeloma: from the discovery of tumor
      associated antigens to clinical trials.
AB  - Tumors aberrantly express tumor-associated antigens that can be specifically
      recognized by T-cells, thereby providing a scientific rationale for the design
      and clinical testing of immunotherapeutic strategies targeting these antigens.
      Multiple myeloma is a fatal hematologic malignancy. Here, we review techniques to
      discover new tumor-associated antigens in multiple myeloma and the latest
      immunotherapeutic strategies employed in this disease.

PMID- 17558745
TI  - Tumor-associated antigens and biomarkers in cancer and immune therapy.
AB  - Cancer has currently overtaken heart disease as the major cause of mortality in
      the United States. The Human Genome Project, advances in informatics,
      miniaturization of sample collection, and increased knowledge of cell signaling
      pathways has revolutionized the study of disease. Genomics, proteomics, and
      metabolomics are currently being used to develop molecular signatures for disease
      diagnosis, prognosis, and therapeutic efficacy. Tumor-associated antigens
      discovered by these methods are being used to develop passive (humoral) as well
      as active immunotherapy strategies to stimulate the immune system. Development
      and validation of biomarkers on a parallel track with therapeutics can speed
      development times by accurate screening of patient populations and substituting
      surrogate markers that correlate well with clinical outcomes.

PMID- 17558746
TI  - Dynamics of 15N natural abundance in wood-decomposing fungi and their
      ecophysiological implications.
AB  - Nine species of basidiomycota and one species of ascomycota were grown in an
      ammonium sulphate media and on beech wood; and the general (15)N dynamic patterns
      of the hyphae were examined. The fungal body initially became depleted in (15)N
      in both the types of incubation. However, the underlying mechanisms were quite
      different, that is, significant fungal (15)N drop on the beech wood is associated
      with the fungal N reallocation and the uptake of atmospheric ammonia and/or
      NO(x), in addition to isotope fractionation during assimilation. Although the
      (15)N values of the wood-decomposing basidiocarps were generally close to the
      (15)N values of the wood, it does not always indicate that the wood derived N was
      the sole N source for the fungi throughout the growth periods as shown in our
      wood-decomposing experiment.

PMID- 17558747
TI  - Effects of natural environmental factors on delta13C of lichens.
AB  - This preliminary study was designed to determine the extent to which the carbon
      isotope ratio in four species of lichens was influenced by such features as
      humidity, rainfall, radioactivity, and air quality. The sampling sites were
      selected to be at a great distance from any pollution. At the time of sampling,
      field data (temperature, relative humidity, average monthly precipitation, and
      radioactivity) were recorded. delta(13)C in whole lichen specimens were
      determined using standard mass spectrometric techniques with a standard deviation
      of+/-0.3 per thousand. We have found a weak but negative correlation between
      delta(13)C and relative humidity, and a positive correlation between delta(13)C
      and average monthly precipitation at the studied sites. The effects were minor,
      of the order of 1.5 per thousand for all the lichens. We have examined the
      correlation between (137)Cs activity concentration of the studied lichens and
      delta(13)C of these lichens, and we have suggested that fixation of radiocesium
      does not alter photosynthesis rate. There was a delta(13)C variation with the
      altitude gradient with less negative delta(13)C values at higher altitude. It is
      possible that this difference is caused by the ozone and occurred at the high
      elevations.

PMID- 17558748
TI  - Effect of radioactive and non-radioactive mercury on wheat germination and the
      anti-toxic role of glutathione.
AB  - Studies to test the noxious effect of mercury ions on wheat germination and
      seedling growth showed that germination rate, shoot length, and fresh weights
      varied as a function of their concentration in the treatment solutions. At the
      same concentration, the radioactive mercury proved to be more harmful to the
      living seeds and seedlings. The detoxification action of glutathione for both
      radioactive and non-radioactive mercury was also followed. After a seven-day
      period of germination in the presence of the investigated compounds, the wheat
      plantlets were cut from the seeds, and their height, weight, and residual
      radioactivity were measured. The shoot length decreased from 8.1 (blank) to 4.6
      cm (non-radioactive mercury) or even to 2.5 cm ((203)Hg), while glutathione had
      both an anti-toxic and an anti-radiotoxic effect (6.4 and 6.0 cm, respectively).
      The root weight of the lot decreased from 1.7 to 0.7 g and 0.4 g, respectively,
      while glutathione showed a healing action (1.5 and 1.7 g). The radioactive ions
      accumulated especially in roots (35.5 %), and less in shoots (11.2 %). Results
      were statistically validated.

PMID- 17558749
TI  - 13C discriminations of Pinus sylvestris vs. Pinus ponderosa at a dry site in
      Brandenburg (eastern Germany): 100-year growth comparison.
AB  - The carbon isotope composition (delta(13)C, per thousand) and discrimination
      (Delta, per thousand) of old grown North American Pinus ponderosa Dougl. Ex P. et
      C. Laws. and European Pinus sylvestris L. were determined using trees grown under
      almost identical growing conditions in a mixed stand in Bralitz, Northeast
      Germany. Single-tree delta(13)C analyses of tree-ring cellulose of both species
      were carried out at a yearly resolution for the period 1901-2001 and the results
      compared with growth (basal area increment). Annual mean delta(13)C values for P.
      ponderosa ranged from-21.6 per thousand to-25.2 per thousand and for P.
      sylvestris from-21.4 per thousand to-24.4 per thousand. Accordingly, (13)C
      discrimination (Delta) showed higher values for P. ponderosa throughout the
      investigation period. Five characteristic periods of Delta were identified for
      both the tree species, reflecting positive and negative influences of
      environmental factors. Good growing conditions such as after-thinning events had
      a positive effect on Delta, reflecting higher values, while poor conditions like
      aridity and air pollution had a negative influence, reflecting lower values. The
      dynamics of Delta were likewise reflected in the growth (basal area increment,
      BAI). Higher (13)C discrimination values of P. ponderosa led to higher BAIs of P.
      ponderosa in comparison with P. sylvestris. Correlation function analyses
      confirmed that P. sylvestris was more dependent on precipitation than P.
      ponderosa, which showed a closer relationship with temperature. The results
      confirm that under predominantly dry growing conditions, P. ponderosa showed
      better growth performance than P. sylvestris, indicating better common intrinsic
      water-use efficiency and, therefore, higher rates of net photosynthesis at a
      given transpiration. In view of the prospect of climate change, the results are
      very significant for assessing both trees' physiological properties and, hence,
      their potential for coping with future growing conditions.

PMID- 17558750
TI  - Dietary back-calculation using stable isotopes: can activities of enzymes
      involved in amino acid metabolism be used to improve estimates of trophic shifts
      in fish?
AB  - The aim of this study was (1) to assess the effects of dietary protein content
      and feeding level on trophic shifts of C and N isotopes (Delta delta(13)C(tissue
      diet) and Delta delta(15)N(tissue-diet)) and (2) to test whether the measurement
      of the activities of two enzymes involved in the metabolism of amino acids could
      improve the accuracy of estimation of the trophic shifts of C and N isotopes. For
      this, 36 Nile tilapia (Oreochromis niloticus) were kept under controlled
      conditions for 8 weeks and fed at three different levels (2, 4 and 8 g kg(-0.8)
      d(-1)) with three diets differing in their protein content only (20, 29 and 39
      %). For each fish, food to fish body trophic shifts of C and N isotopes were
      measured as well as the hepatic activities of aspartate aminotransferase (ASAT)
      and glutamate dehydrogenase (GDH). The feeding level affected the activities of
      ASAT and GDH as well as the trophic shifts of C and N isotopes significantly but
      the dietary protein content had no significant effect except on the specific
      activity of ASAT. Fish fed at the lowest level had significantly higher trophic
      shifts of C and N isotopes than fish fed at higher levels. The trophic shifts
      were significantly lower in fish with a high protein utilisation. Values of the
      'goodness-of-fit' for linear regressions between enzyme activities and trophic
      shifts were low. Thus, activities of ASAT and GDH are not suitable for predicting
      estimates of trophic shifts in situations where the amount of food consumed or
      the dietary protein content is not known. In further studies, activities of
      enzymes involved in the metabolism of amino acids combined with measurements of
      the activities of other enzymes should be used to try and improve the accuracy of
      estimates of trophic shifts.

PMID- 17558751
TI  - Effect of different ratios of wheat to corn flour in the diet on the development
      and isotopic composition (delta13C, delta15N) of the red flour beetle Tribolium
      castaneum.
AB  - The back-calculation of the diet is a common application of stable isotopes in
      animal ecology. The method is based on a predictable relation between the
      isotopic signature of the diet and the animal's tissues. Frequently, the
      assumption of a constant difference in isotopic signatures (trophic shift) is
      made. Carbon isotopic ratios of C(3) and C(4) plants differ by approximately 10
      per thousand, making wheat (C(3)-plant) and corn (C(4)-plant) ideal materials for
      isotopic studies in nutritional ecology and especially for testing the back
      calculation method. In this experiment, red flour beetles, Tribolium castaneum,
      were reared on wheat flour, corn flour and three different mixtures thereof,
      either in pure flour or with the addition of yeast inoculum or yeast grains.
      Development of T. castaneum on these experimental diets was monitored, and
      isotopic signatures of carbon and nitrogen in emerging adults were analysed. The
      values of trophic shift of C and N isotopes for wheat and corn flour were
      different, and the values for the mixtures did not correspond to those expected
      from a linear mixing model. The latter can be taken as an indication that the
      tiny larvae of T. castaneum may be capable of differentiating between particles
      of wheat and corn flour, making this animal model unsuitable for testing the back
      calculation method.

PMID- 17558752
TI  - Expression of maternal isotopes in offspring: implications for interpreting
      ontogenetic shifts in isotopic composition of consumer tissues.
AB  - When evaluating ontogenetic shifts in isotopic composition of consumer tissues
      within the context of a dietary analysis, the isotopic starting point of
      consumers in the population should not be ignored. Neonate isotopic composition
      may be different from that of juveniles and adults; in general, neonate tissues
      are built from maternal resources rather than food resources. Thus, the range of
      isotope values observed within a population of consumers may be significantly
      impacted by consumer isotope ratios at birth. Long-term goals of my research
      involve the use of stable isotopes to assess the role diet plays in driving
      population level differences in life history and demography observed among three
      pigmy rattlesnake (Sistrurus miliarius; family Viperidae) populations. For
      meaningful interpretation of field-collected data, it was important to determine
      starting (i.e., at birth) isotopic compositions of rattlesnakes from the study
      populations. We quantified isotopic composition of pregnant pigmy rattlesnake
      scale tissue, isotopic composition of neonate scale tissue and the degree that
      neonate scale tissue isotopic composition reflected the isotopic composition of
      maternal scale tissue. Collectively, neonate isotopic composition was highly
      variable among-litters; average litter delta(13)C values spanned 7 per thousand
      and average litter delta(15)N values spanned 2.8 per thousand. Over 95 % of the
      variation in offspring isotopic composition was expressed among litters. Thus,
      high levels of among-litter isotopic variation were largely due to the retention
      of a maternal signal. Results of the enclosure study suggest that highly variable
      isotopic signatures in young animals within field populations could easily
      reflect the retention of a maternal signal rather than differences in resource
      utilisation among younger snakes.

PMID- 17558753
TI  - Anomalous fluoride concentration in groundwater - is it natural or pollution? A
      stable isotope approach.
AB  - Fluoride anomalies (up to 11 mg/l) have been detected in groundwater of the
      central region of Rio Grande do Sul State, Southern Brazil, in an area where
      fluorosis is endemic. Two hypotheses are investigated concerning the fluoride
      origin: lithochemical affiliation from regional rock or contamination by
      fertilisers application. These hypotheses are discussed based on the stable
      isotope data of water, nitrate, and sulphate, which indicates that the local
      precipitation is the main groundwater recharge source. The isotopic composition
      of groundwater sulphate is similar to that of fertiliser sulphate. However, a
      conclusive assignment of groundwater sulphate to fertiliser origin is not
      indicated because further possible sulphate sources fall into the same isotopic
      range. In contrast, the isotopic composition of dissolved nitrate suggests that
      there is no direct relationship to the use of NPK fertilisers. Hence, an origin
      of the high fluoride content in groundwater related to long-term rock-water
      interactions seems likely.

PMID- 17558756
TI  - Evaluation of procollagen I deposition after intense pulsed light treatments at
      varying parameters in a porcine model.
AB  - Several lasers and light sources have been reported to induce dermal collagen
      remodeling without damaging the epidermis. The intense pulsed light (IPL) system,
      which emits polychromatic light of wavelengths between 560 and 1200 nm belongs to
      this group of increasingly popular non-ablative skin rejuvenation devices.
      Various IPL treatment parameters can be adjusted to achieve optimal dermal
      remodeling and clinical improvement. The aim of this study was to evaluate
      variations in IPL treatment parameters and the effect on procollagen I
      deposition. Marked areas of a live Yorkshire pig's flank skin were irradiated
      with a single or double pass of an IPL source using a fluence of 30 or 40 J/cm2
      and a cut-off wavelength filter of 590 nm. Skin biopsies were performed on
      postoperative days 1, 7, 14, 21, and 42. A statistically significant increase in
      procollagen I in treated versus untreated sites was found on postoperative days
      21 and 42, but not earlier. There was a uniformly significant increase in
      procollagen I on day 42 using the 590 nm filter at both 30 and 40 J/cm2 with
      either a single or double pass. The increase in procollagen was greater with a
      fluence of 40 J/cm2 compared with 30 J/cm2.

PMID- 17558757
TI  - Prospective clinical and histological study to evaluate the efficacy and safety
      of a targeted high-intensity narrow band UVB/UVA1 therapy for striae alba.
AB  - OBJECTIVE: The purpose of this study was to determine the efficacy and safety of
      a targeted narrow band UVB/UVA1 therapy for the treatment of striae alba.
      METHODS: Fourteen individuals with skin types II-VI were enrolled in this 22-week
      trial that consisted of up to 10 treatments with a combination of UVB/UVA1
      (MultiClear, Curelight Ltd, Israel). Participants were treated with a maximum of
      10 treatments unless 100% repigmentation of stretch was achieved prior to the
      tenth treatment. Biopsies were taken from willing participants at baseline,
      immediately after the final treatment and 12 weeks after the last treatment.
      RESULTS: Nine participants completed all treatment visits. After the final
      treatment, all the participants had >51% repigmentation of the treated striae. At
      the 4-week follow-up visit, 67% of participants had greater than 51% improvement,
      and 56% had greater than 51% improvement at the 8-week and 12-week follow-ups.
      Hyperpigmentation of striae was seen in >50% of the participants treated. The
      pretreatment biopsies were confirmatory of striae. There were no diagnostic light
      microscopic differences in the 4-week post-treatment biopsy set available in one
      patient. CONCLUSION: This high intensity UVB?UVA1 device is an effective and safe
      modality for the short-term repigmentation of hypopigmented stretch marks.
      Additional morphologic studies over time are needed to confirm these clinical
      findings.

PMID- 17558758
TI  - The effectiveness and safety of topical PhotoActif phosphatidylcholine-based anti
      cellulite gel and LED (red and near-infrared) light on Grade II-III thigh
      cellulite: a randomized, double-blinded study.
AB  - BACKGROUND: Cellulite of the upper lateral and posterior thighs and lower
      buttocks represents a common, physiological and unwanted condition whose
      etiologies and effective management are subjects of continued debate. OBJECTIVE:
      The purpose of this controlled, double-blinded study is to evaluate the efficacy
      and safety of a novel phosphatidylcholine-based, cosmeceutical anti-cellulite gel
      combined with a light-emitting diode (LED) array at the wavelengths of red (660
      nm) and near-infrared (950 nm), designed to counter the possible mechanisms that
      purportedly accentuate the presence of thigh cellulite. METHODS: Nine healthy
      female volunteers with Grade II-III thigh cellulite were randomly treated twice
      daily with an active gel on one thigh and a placebo gel on the control thigh for
      3 months. Twice weekly, each thigh was exposed for a 15-minute treatment with LED
      light for a total of 24 treatments. At 0, 6, and 12 weeks of the study the
      following clinical determinants were obtained: standardized digital photography,
      height and weight measurements, standardized thigh circumference tape
      measurements, pinch testing, body mass index (kg/m2), body fat analysis (Futrex
      5500/XL near-infrared analyzer), and digital high-resolution ultrasound imaging
      of the dermal-adiposal border. In selected patients, full-thickness biopsies of
      the placebo and active-treated sites were obtained. At 18 months, repeat
      standardized digital photography, height and weight measurements, and body mass
      index measurements were obtained. RESULTS: At the end of 3 months, eight of nine
      thighs treated with the phosphatidylcholine-based, anti-cellulite gel and LED
      treatments were downgraded to a lower cellulite grade by clinical examination,
      digital photography, and pinch test assessment. Digital ultrasound at the dermal
      adiposal interface demonstrated not only a statistically significant reduction of
      immediate hypodermal depth, but also less echo-like intrusions into the dermal
      layer. Three of six biopsies from thighs treated for 3 months with the active gel
      and LED treatments demonstrated less intrusion of subcutaneous fat into the
      papillary and reticular dermis. In nine placebo and LED-treated thighs and one of
      the actively treated thighs, minimal clinical changes were observed or measured
      by the clinical determinants throughout the 3-month study. At the month-18
      evaluation period for the eight responsive thighs, five thighs reverted back to
      their original cellulite grading, while three thighs continued to maintain their
      improved status. Patients experienced minimal and transient side effects that
      included puritus, erythema and swelling. CONCLUSIONS: The results of this small
      but well-documented, randomized, double-blinded study affirms that eight of nine
      thighs with Grade II-III cellulite responded positively to a novel, combined 3
      month treatment program of a phosphatidylcholine-based, anti-cellulite gel and
      LED exposure, as determined by the clinical determinants obtained. Patients
      experienced minimal and transient side effects. At the month-18 evaluation period
      (15 months after treatment), five responsive thighs reverted back to their
      original cellulite grading, indicating a need for maintenance treatment. Future
      studies are needed to verify these tentative positive observations.

PMID- 17558759
TI  - A comparison between CO2 laser surgery with and without lateral fold vaporization
      for ingrowing toenails.
AB  - BACKGROUND: An ingrowing toenail is an excessive lateral nail growth into the
      nail fold. It acts as a foreign body and exerts a local pressure sore-like
      effect, which may result in inflammation and granulation. Several treatment
      modalities exist, including chemical ablation and different surgical procedures.
      Here we describe and compare a simple and effective method of partial
      matricectomy using the CO2 laser (group A) versus a similar method with the
      addition of lateral nail fold vaporization (group B). OBJECTIVE: Outcome
      evaluation of a modified laser treatment modality for ingrowing toenails and
      determination of the role of lateral fold vaporization in reducing the recurrence
      of symptoms. METHODS: Forty patients (mean age 32.45 years) were treated with CO2
      laser ablation of toenails between 1999 and 2005 by four physicians. One
      physician implemented a method that includes lateral nail fold vaporization and
      resection of the nail segment with its nail bed from 1999 to 2005. Three
      physicians implemented a similar technique but without lateral fold vaporization
      between 1999 and 2003, and added lateral fold vaporization to the performed
      procedure starting in 2004. RESULTS: The recurrence rate was 37.5% in group A and
      6.2% in group B. The overall average disease-free follow-up period was 42.2
      months. CONCLUSION: The use of CO2 laser in the treatment of ingrowing toenails
      offers an effective modality. We demonstrate the importance of lateral fold
      vaporization with the CO2 laser both in improving efficacy and in decreasing
      recurrence rates over a long follow-up period.

PMID- 17558760
TI  - Fractional photothermolysis for the treatment of telangiectatic matting: a case
      report.
AB  - BACKGROUND: Recent reports have demonstrated clinical and histologic evidence of
      the potential benefit of fractional photothermolysis (1550 nm Fraxel SR laser)
      for the treatment of dermal vascular lesions. This report evaluated the potential
      efficacy of fractional photothermolysis for the treatment of matted
      telangiectasias. METHODS: A 62-year-old female, Fitzpatrick skin type III, with
      matted telangiectasias on her right medial thigh underwent five successive
      treatments at monthly intervals with the 1550 nm Fraxel SR laser. Digital
      photographs were taken prior to each treatment and at 6 months after the last
      treatment. Clinical assessments were performed by a non-treating physician.
      RESULTS: Clinical assessment 6 months after the last treatment with the Fraxel SR
      laser revealed marked improvement in the clinical appearance of the matted
      telangiectasias. The patient's degree of satisfaction paralleled the physician's
      assessment of improvement. Side effects were limited to mild pain during
      treatment and mild, transient post-treatment erythema and edema. CONCLUSION:
      Fractional photothermolysis is a potentially effective modality for the treatment
      of matted telangiectasias and warrants further studies. No long-term adverse
      events were noted and the safety profile appears to be fairly broad.

PMID- 17558761
TI  - Angiolymphoid hyperplasia with eosinophilia: successful treatment with the Nd:YAG
      laser.
AB  - Angiolymphoid hyperplasia with eosinophilia (ALHE) is an uncommon idiopathic
      proliferation of blood vessels that manifests in adults as isolated or grouped
      papules, plaques, or nodules in the skin of the head and neck. We describe the
      case of a 31-year-old woman with a 3-year history of persistent ALHE, located on
      the tragus of her right ear, with no sign of spontaneous regression over a period
      of 3-6 months and refractory to intralesional corticosteroids. We report the
      successful use of the Nd:YAG laser for this condition, which offered excellent
      symptomatic and cosmetic results and suggests the consideration of this modality
      in the treatment of ALHE.

PMID- 17558762
TI  - Vascular lasers and IPLS: guidelines for care from the European Society for Laser
      Dermatology (ESLD).
AB  - Dermatology and dermatologic surgery have rapidly evolved during the last two
      decades thanks to the numerous technological and scientific acquisitions focused
      on improved precision in the diagnosis and treatment of skin alterations. Given
      the proliferation of new devices for the treatment of vascular lesions, we have
      considerably changed our treatment approach. Lasers and non-coherent intense
      pulse light sources (IPLS) are based on the principle of selective
      photothermolysis and can be used for the treatment of many vascular skin lesions.
      A variety of lasers has recently been developed for the treatment of congenital
      and acquired vascular lesions which incorporate these concepts into their design.
      The list is a long one and includes pulsed dye (FPDL, APDL) lasers (577 nm, 585
      nm and 595 nm), KTP lasers (532 nm), long pulsed alexandrite lasers (755 nm),
      pulsed diode lasers (in the range of 800 to 900 nm), long pulsed 1064 Nd:YAG
      lasers and intense pulsed light sources (IPLS, also called flash-lights or pulsed
      light sources). Several vascular lasers (such as argon, tunable dye, copper
      vapour, krypton lasers) which were used in the past are no longer useful as they
      pose a higher risk of complications such as dyschromia (hypopigmentation or
      hyperpigmentation) and scarring. By properly selecting the wavelength which is
      maximally absorbed by the target--also called the chromophore (haemoglobin in the
      red blood cells within the vessels)--and a corresponding pulse duration which is
      shorter than the thermal relaxation time of that target, the target can be
      preferentially injured without transferring significant amounts of energy to
      surrounding tissues (epidermis and surrounding dermal tissue). Larger structures
      require more time for sufficient heat absorption. Therefore, a longer laser-pulse
      duration has to be used. In addition, more deeply situated vessels require the
      use of longer laser wavelengths (in the infrared range) which can penetrate
      deeper into the skin. Although laser and light sources are very popular due to
      their non-invading nature, caution should be considered by practitioners and
      patients to avoid permanent side effects. These guidelines focus on patient
      selection and treatment protocol in order to provide safe and effective
      treatment. Physicians should always make the indication for the treatment and are
      responsible for setting the machine for each individual patient and each
      individual treatment. The type of laser or IPLS and their specific parameters
      must be adapted to the indication (such as the vessel's characteristics, e.g.
      diameter, colour and depth, the Fitzpatrick skin type). Treatments should start
      on a test patch and a treatment grid can improve accuracy. Cooling as well as a
      reduction of the fluence will prevent adverse effects such as pigment alteration
      and scar formation. A different number of repeated treatments should be done to
      achieve complete results of different vascular conditions. Sunscreen use before
      and after treatment will produce and maintain untanned skin. Individuals with
      dark skin, and especially tanned patients, are at higher risk for pigmentary
      changes and scars after the laser or IPLS treatment.

PMID- 17558763
TI  - In situ bioremediation of groundwater contaminated with petroleum constituents
      using oxygen release compounds (ORCs).
AB  - Over the past 5 years, the use of in situ biological remediation methods has
      gained acceptance for the biological degradation of petroleum hydrocarbons and
      chlorinated solvents in the groundwater. Application of slow-release compounds
      such as Oxygen Release Compound (ORC) and Hydrogen Releasing Compounds have been
      used routinely as remediation tools. This paper describes the implementation of
      an in situ bioremediation scheme to address the petroleum constituents in the
      groundwater at the site of a former gasoline station. Site investigations had
      indicated that groundwater beneath the site was contaminated with up to 34,300
      microg/L benzene, toluene, ethylbenzene and xylenes (BTEX). The remedial scheme
      involved the installation of the four monitoring wells, monitoring and sampling
      of the wells and the application of ORCs into the Area of Concern (AOC). The
      results indicate that levels of petroleum constituents continue to be present in
      groundwater beneath the site after ORC injection. However, over time the levels
      of BTEX have significantly decreased. Kinetic study showed that the removal of
      BTEX fits a zero-order kinetic model for each monitoring well under enhanced
      oxidized conditions. The compound with the highest biodegradation rate constant
      was m,p-xylene in monitoring wells MW-2, MW-3 and MW-4.

PMID- 17558764
TI  - Fractionation of mercury in sediments from coastal zone inundated by tsunami and
      in freshwater sediments from the rivers.
AB  - The study was undertaken to compare the mobility and bioavailability of mercury
      in tsunami sediments from the coastal zone of Thailand left after the 26 December
      2004 tsunami event and freshwater sediments from the Vistula and the Warta rivers
      in Poland. The mobility and bioavailability of mercury in these sediments were
      determined by sequential extraction method. The environmental
      similarity/differences were estimated by statistical tests and cluster imaging
      technique. The coastal post-tsunami sediments were characterized by higher
      contributions of organomercury species (median 14%) and mercury sulphide (75%)
      than the freshwater sediments (5.4-9.3% and 60-68%, respectively), however, the
      contributions of water-soluble fraction (0.6%) and mercury bound to humic matter
      (7.6%) in the former was lower. In the river sediments the contributions of water
      soluble mercury and mercury bound to humic matter were: 2.0-5.7% and 16-24%,
      respectively. The contributions of acid-soluble mercury were generally very low,
      but relatively higher in the post-tsunami sediments (0.7%) than in the freshwater
      sediments (0.3-0.4%).

PMID- 17558765
TI  - Characterization of mercury and other heavy metals in sediment of an ecological
      important backwater area of River Tisza (Hungary).
AB  - Sediment from a representative and ecologically important backwater wetland under
      the influence of River Tisza (Hungary) was chemically characterized for sediment
      pollutants. Phosphine production potential, methyl mercury, mercury, and other
      heavy metals were determined along with other sediment chemical and physical
      properties. The wetland site, which is relatively isolated, represents an
      important bird reserve and nature conservation area. Methyl mercury and total
      mercury content was also low reflecting little mercury pollution in the sediment.
      Results of heavy metal analysis showed that only copper was elevated with
      concentration slightly above the reported levels considered excessive in soils
      and sediments. Other sediment properties were in normal range except boron
      content, which was high. Results show sediment were relatively unpolluted but
      should be routinely monitored to insure that this ecologically important area
      remains environmentally safe for future generation.

PMID- 17558766
TI  - Mercury-induced alterations in rat kidneys and testes in vivo.
AB  - In this study effects of mercury administration on the kidney and testicular
      structure of adult rats were evaluated. Rats received mercury (HgCl2) in single
      intraperitoneal dose 20 mg HgCl2 (group A), 10 mg HgCl2 (group B) and 5 mg HgCl2
      (group C) per kilogram of body weight and were killed after 48 hours following
      mercury administration. After the preparation of histological samples the results
      were compared with control group (K). In kidney decreased diameters of glomeruli
      and renal corpuscles, damaged tubules with affected quality of tubular cells and
      infiltration of interstitium were detected. Quantitative analysis demonstrated
      increased relative volume of tubules and renal corpuscles. Also the number of
      nuclei and glomeruli was increased in all experimental groups. The diameter of
      glomeruli and renal corpuscles was decreased. In testis undulation of basal
      membrane, dilatation of blood vessels in interstitium and occurrence of empty
      spaces in germinal epithelium were observed. Decreased relative volume of
      germinal epithelium, increased relative volume of interstitium and increased
      apoptosis occurrence suggest damaged interstitium and revealed occurrence of
      edemas. The relative volume of seminiferous tubules showed higher luminization.
      The number of nuclei was decreased in all experimental groups what is in positive
      relation with occurrence of empty spaces. Also other evaluated criteria
      demonstrated significant differences between control group and experimental
      groups. This study reports a negative effect of mercury on the structure and
      function of kidney and testes.

PMID- 17558767
TI  - Laser-based sensor for detection of hazardous gases in the air using waveguide
      CO2 laser.
AB  - A spectrometer based on the principle of photoacoustic spectroscopy has been
      developed recently at our laboratory for the detection of hazardous gases such as
      O3, C2H4, SO2, NO2 and SF6. In most of our earlier works, we employed a
      mechanical chopper to modulate the laser beam and this chopper modulation has the
      crucial disadvantage of instability in the chopper frequency. Even a minor shift
      of about 1 Hz in the modulation frequency could significantly reduce the
      photoacoustic signal by an order of magnitude at the acoustic resonant mode of
      the photoacoustic cell. To overcome this problem, we developed a photoacoustic
      spectrometer where a wave guided CW CO2 laser beam is modulated electronically
      with the external frequency generator. Our preliminary results show that the
      electronic modulation of CO2 laser beam improved the sensitivity of our
      spectrometer by a factor of 6. The parametric dependence of photoacoustic signal
      on laser power, modulation frequency and trace gas concentration, was
      investigated and the comparison between the two modulation techniques is
      presented in this paper for detection of trace gases such as C2H4.

PMID- 17558768
TI  - Detection of contaminants in ore samples using laser-induced breakdown
      spectroscopy.
AB  - Laser-induced breakdown spectroscopy (LIBS) has been applied for the
      determination of contaminants present in ore samples. The plasma was generated by
      focusing a pulsed Nd:YAG laser radiation at 1064 nm wavelength on the ore sample
      collected from one of the open-pit mines located in Saudi Arabia. The
      concentrations in this ore sample of different elements of environmental
      significance like Cu, Cr, Ca, Mg, Zn, Ti, Si, Fe and Al were determined by
      spectral analysis. Parametric dependence for improvement of LIBS sensitivity was
      carried out. The LIBS results were compared with the results obtained using other
      analytical techniques such as the inductively coupled plasma emission
      spectroscopy (ICP-AES). Limits of detection (LOD) of our LIBS system were also
      calculated for the elements under investigation.

PMID- 17558769
TI  - Comparative sensitivity in Chinese rare minnow (Gobiocypris rarus) and Japanese
      Medaka (Oryzias latipes) exposed to ethinylestradiol.
AB  - Morphological and biochemical indices, including hepatosomatic index,
      gonadosomatic index, and vitellogenin (VTG) induction, were compared between two
      teleostean species to determine their relative sensitivity of exposure to 17
      alpha -ethinylestradiol (EE2). Chinese rare minnow (Gobiocypris rarus) and
      Japanese medaka (Oryzias latipes) were exposed to aqueous concentrations of EE2
      ranging from 0.2 to 100 ng/L for 21 days. A stronger liver response to EE2 in
      Chinese rare minnow was observed than that in Japanese medaka. In Japanese
      medaka, significantly increased male GSI could be observed at 50 and 100 ngEE2/L.
      The semi-quantitative estimation by integrated optic density following
      electrophoresis showed that exposure of male Chinese rare minnow and Japanese
      medaka to EE2 resulted in significant (P<0.05) induction of VTG at 0.2 and 2
      ngEE2/l, respectively. It indicated that the sensitivity of Chinese rare minnow
      to the stress of EE2 is about 10-fold greater than that of Japanese medaka.

PMID- 17558770
TI  - Particulates and bacteria removal by ceramic microfiltration, UV photolysis, and
      their combination.
AB  - Membrane microfiltration (MF) or ultrafiltration (UF) systems of activated sludge
      is crucial part of a bioreactor process used in municipal wastewater treatment.
      In this study, both cylindrical and flat sheet ceramic membranes were used to
      treat municipal wastewaters. The effects of removing water turbidity and coliform
      bacteria from an artificial wastewater were studied by performing batch
      experiments by MF and ultraviolet (UV) photolysis of 254 nm wavelength. It was
      shown that the microfiltration had a high effect of suspended solid removal.
      However, the effect of bacteria removal was limited so that the rate of cfu
      removal was approximately 61%. Combined consecutive processes in the treatment
      (MF/UV and UV/MF) confirmed that a specific porosity of the ceramic filter for
      bacteria removal was required. The continuous membrane bioreactor (MBR) tests
      performed by using a MF membrane with the pore size of 0.2 microm showed that
      particulate matter and microorganisms found in municipal wastewater could be
      effectively removed. Turbidity was decreased from 4.50 to 0.05 NTU, with a
      removal efficiency of greater than 98%. The permeate total suspended solid (TSS)
      content for the whole run was below 5 mgL-1. The density of total coliforms was
      decreased more than four orders of magnitude (from around 1x10(5) mL-1 to less
      than 5 mL-1 in the effluent).

PMID- 17558771
TI  - Methanogenic community change in a full-scale UASB reactor operated at a low F/M
      ratio.
AB  - A full-scale upflow anaerobic sludge blanket (UASB) reactor was investigated in
      terms of archaeal composition, acetoclastic methanogenic capacity and performance
      over a 2-year period. Performance of the reactor in terms of COD removal
      efficiency varied between 60% and 80% at organic loading rates (OLRs) in the
      range of 2.5-12 kg COD m-3 d-1. The reactor had been operated under a F/M (food
      to microorganisms) ratio of 0.02-0.03 gCOD gTVS-1 d-1, which is much lower than
      the typical values reported for similar reactors. According to specific
      methanogenic activity (SMA) tests the anaerobic sludge was operating at only 12
      34% of its potential acetoclastic methanogenic capacity. These results
      demonstrated that the UASB reactor was under loaded compared to its maximum
      loading capacity. All other operational parameters had been maintained within
      their desired ranges. The SMA test and Fluorescence in situ hybridization (FISH)
      results revealed that a decrease in the acetoclastic methanogenic activity of the
      UASB sludge from 344 mL CH4 gTVS-1 d-1 to 109 mL CH4 gTVS-1 d-1 coincided with a
      decrease in the relative abundance of acetoclastic Methanosaeta from 90%+/-1.2 to
      79%+/-1.4 of the archaeal population, and an increase in the relative abundance
      of hydrogenotrophic Methanobacteriales from non-detectable levels to 24%+/-0.7%
      of the archaeal population during the 2-year operation of the reactor. The
      relative abundance of archaeal cells within the UASB sludge was in the range of
      15-17%.

PMID- 17558772
TI  - Influence of anaerobic co-digestion of sewage and brewery sludges on biogas
      production and sludge quality.
AB  - This research investigated operating parameters and treatment efficiency for the
      digestion of sewage and brewery sludge. The prime objective of this study was to
      enhance the quality of treated sludge for use as agriculture fertilizer and to
      enhance biogas production, a by-product that can be used as an energy source.
      Three bench-scale completely stirred tank reactor (CSTR) anaerobic digesters were
      operated at mesophilic condition (36+/-0.2 degrees C). A mixture of sewage and
      brewery sludge were used as substrates at ratios of 100:0, 75:25, 50:50, 25:75
      and 0:100, based on wet weight basis (w/w). For each digester, the solids
      retention times (SRT) were 20 days. The organic loading and volatile solids
      loading were between 1.3-2.2 kg chemical oxygen demand (COD)/m3/day and 0.9-1.5
      kg/m3/day, respectively. The digester fed with brewery sludge as co-substrate
      yielded higher treatment efficiency than sewage sludge alone. The removal
      efficiencies measured in terms of soluble chemical oxygen demand (SCOD) and total
      chemical oxygen demands (TCOD) ranged from 40% to 75% and 22% to 35%,
      respectively. Higher SCOD and TCOD removal efficiencies were obtained when higher
      fractions of brewery sludge was added to the substrate mixture. Removal
      efficiency was lowest for sewage sludge alone. Measured volatile solid (VS)
      reduction ranged from 15% to 20%. Adding a higher fraction of brewery sludge to
      the mixture increased the VS reduction percentage. The biogas production and
      methane yield also increased with increase in brewery sludge addition to the
      digester mixture. The methane content present in biogas of each digester exceeded
      70% indicating the system was functioning as an anaerobic process. Likewise the
      ratio of brewery sewage influenced not only the treatment efficiency but also
      improved quality of treated sludge by lowering number of pathogen (less than 2
      MPN/g of dried sludge) and maintaining a high nutrient concentration of nitrogen
      (N) 3.2-4.2%, phosphorus (P) 1.9-3.2% and potassium (K) 0.95-0.96%. The heavy
      metals, chromium (Cr) and copper (Cu) remaining in digested sludge were present
      at relatively high levels (Cr 1,849-4,230 and Cu 930-2,526 mg/kg dried sludge).
      The metals were present as organic matter-bound and sulfide-bound fractions that
      are not soluble and available. The digested sludge could be safely applied to
      soil as a plant nutrient source, without fecal coliforms or heavy metals risk. A
      sludge mixture ratio of 25:75 (sewage:brewery), which generated the higher
      nutrient concentrations (N=4.22%, P=3.20% and K=0.95%), biogas production and
      treatment efficiency meet the Bangkok Metropolitan Administration (BMA) safety
      guidelines required for agricultural application. Biogas production and methane
      at the 25:75 ratio (sewage:brewery) yielded highest amount of VSremoved (0.65
      m3/kg) and CODremoved (220 L/kg), respectively.

PMID- 17558773
TI  - Biogas production from water hyacinth (Eichhornia crassipes (Mart.) Solms) grown
      under different nitrogen concentrations.
AB  - This paper reports the biogas production from water hyacinth (Eichhornia
      crassipes (Mart.) Solms) grown under different nitrogen concentrations of 1-fold
      [28 mg/L of total nitrogen (TN)], 2-fold, 1/2-fold, 1/4-fold and 1/8-fold and
      plants harvested from a polluted water body. This study was carried out for a
      period of 4 months at ambient mesophilic temperatures of 30.3-31.3 degrees C
      using six 3-barreled batch-fed reactors with the innermost barrel (45 L) being
      used as the digester. There was no marked variation in the C/N ratios of the
      plants cultured under different nitrogen concentrations. The addition of fresh
      cow dung having a low C/N of 8 resulted in a significant reduction in the C/N
      ratios of the water hyacinth substrates. However, gas production commenced 3 days
      after charging the reactors and gas production rates peaked in 4-7 days. The
      volatile solids (VS) degradation and gas production patterns manifested that in
      conventional single-stage batch digesters acidogenesis and methanogenesis of
      water hyacinth requires a retention time of around 27-30 days and 27-51 days,
      respectively. Substrates in the f-1 digester (i.e., the digester containing
      plants grown under 28 TN mg/L) having the lowest VS content of 45.3 g/L with a
      highest C/N ratio of 16 showed fairly higher gas production rates consistently
      (10-27 days) with higher gas yields containing around 50-65% of CH4 (27-51 days).
      Moreover the highest overall VS (81.7%) removal efficiencies were reported from
      the f-1 digester. Fairly higher gas production rates and gas yields with fairly
      higher CH4 contents were also noticed from the f-2 digester containing substrates
      having a C/N of 14 and f-out digester (containing the plants harvested from the
      polluted water body) having the lowest C/N ratio of 9.7 with a fairly high VS
      content of 56 g/L. CH4 production was comparatively low in the f-1/8, f-1/4 and f
      1/2 digesters having VS rich substrates with varying C/N ratios. We conclude that
      water hyacinth could be utilized for biogas production irrespective of the fact
      that the plants are grown under higher or lower nitrogen concentrations and that
      there is no necessity for the C/N ratio to be within the optimum range of 20-32
      required for anaerobic digestion. Further it is concluded that several
      biochemical characteristics of the substrates significantly influences biogas
      production besides the C/N ratio.

PMID- 17558774
TI  - Simulation of water quality and plankton dynamics in the Danshuei River estuary,
      Taiwan.
AB  - An ecosystem model was developed to simulate the water quality and plankton
      dynamics in the Danshuei River estuary, Taiwan. The model simulates the
      hydrodynamics with a laterally integrated 2-dimensional intratidal numerical
      model, which supplies the physical transport processes for simulation of water
      quality and plankton state variables. The application of the model to the
      Danshuei River estuary indicates that the point source loadings are mainly
      responsible for the degraded water quality and very high nutrient concentrations
      in the estuary. The impacts of wastewater discharges are tightly controlled by
      the transport processes. Frequent occurrence of high river flow and flood events
      rapidly cleanses the estuary by flushing out both pollutants and plankton
      populations. The plankton is allowed to grow to significant populations if low
      river flow lasts for a period much longer than the biological time scale.

PMID- 17558775
TI  - Removal of odor using biofilter from duck confinement buildings.
AB  - The poultry and waterfowl industry in the Fraser Valley of British Columbia needs
      to deal with odor emission problems. The objective of this study is to evaluate
      the performance of a pilot-scale biofiltration system for treating odors from the
      exhaust air streams of a commercial duck farm building before their release to
      the atmosphere. A pilot-scale biofiltration system with semi-enclosed wooden
      structure was designed, constructed and installed to treat the exhaust air from
      one of the 12 operating ventilation exhaust fans, having a ventilation rate of
      2.36 m3/s. The empty bed residence time of the biofilter was 5-10 seconds at the
      design flow rate. The biofilter media comprised of 2 parts softwood chips and
      barks to 1 part finished compost. Fabric filters were used for pre-treatment to
      protect the biofilter from clogging by dust particles and feathers. Odor
      reduction was determined by measuring the concentration of the air entering and
      leaving the biofilter via olfactometry analysis. The odor concentration of
      untreated barn air was found to vary from 8553+/-1006 to 12171+/-1575 OU/m3;
      however, the odor concentration was substantially reduced to 420+/-195 OU/m(3)
      after the manure storage was cleaned out at the end of summer. The odor removal
      efficiency of the biofilter system averaged 95+/-3%. The high frequency of
      cleaning and replacement required of the fabric filters would considerably
      increase the operating cost. Alternative methods of dust and odor removal that
      are more cost-effective will need to be investigated in the future.

PMID- 17558776
TI  - A study of dual polymer conditioning of aluminum-based drinking water treatment
      residual.
AB  - Conditioning of an aluminum-based water treatment sludge by single and dual
      polymers was investigated in this study. Capillary suction time (CST), specific
      resistance to filtration (SRF) and settling rate were used to evaluate the sludge
      dewatering characteristics. Sludge dewaterability resulting from single and dual
      polymer conditioning were compared for the purpose of exploring the validity and
      effectiveness of dual polymer conditioning strategy. Unlike activated sludge
      derived from wastewater treatment, results from this study have demonstrated that
      conditioning of the alum sludge by the combined use of an cationic polymer (FO
      4140) followed by an anionic polymer (LT-25) does not exhibit considerable
      advantage in further improvement of sludge dewaterability with comparison of
      single polymer conditioning. This study supports the view that for aluminum-based
      water treatment sludge, inter particle bridging seems to be the dominative
      mechanism and the charge neutralization plays a less important role in the
      conditioning process. In addition, an intrinsic relationship between CST and SRF
      was deducted and tested via the experimental data obtained from the study.

PMID- 17558777
TI  - Evaluation of the quality of the water in El Hondo natural park located in the
      east of Spain.
AB  - The purpose of the present work was to evaluate the quality of the water in El
      Hondo Park, an important wetland located in the east of Spain (province of
      Alicante) and included on the Ramsar List. The influence of the input of
      pollutants was assessed over a 14-month period in order to propose remedial
      action. Three different sources of waters were studied: irrigation water,
      brackish water and reservoir water. The irrigation water was found to have a high
      value of conductivity with high concentrations of Cl-, SO(4)2-, Na+ and K+ due to
      the influence of the brackish water. The concentration of organic matter given as
      CODT (total chemical oxygen demand) was found to be in the range of 70-600 mg/L
      of CODT, which was comparable to low-middle strength wastewater. A high
      concentration of Chlorophyll (a) was found in samples of reservoir water and the
      eutrophication of this water was thus observed. A high linear relationship was
      found among CODT, CODF (filtered COD) and BOD5; among electrical conductivity
      (E.C.), Cl-, SO4(-2), Na+, K+, Ca2+ and Mg2+ and among pH, CO3H- and CO(3)2- in
      all the samples evaluated. Taking this fact into consideration, a simplified
      water quality index (WQI) was calculated. Using this parameter, the quality of
      the water from different sources and its variation during the period evaluated
      was determined to be at a maximum during the months of December to February,
      which coincided with the period of high precipitations and low temperature. The
      highest values of this parameter were found in the samples corresponding to the
      reservoir water while the lowest values were found in the samples of the brackish
      water. By determination of the WQI, the influence of the brackish water on the
      quality of water for irrigation and reservoir waters was confirmed.

PMID- 17558778
TI  - Evaluation of infiltration models in contaminated landscape.
AB  - The infiltration models of Kostiakov, Green-Ampt, and Philip (two and three terms
      equations) were used, calibrated, and evaluated to simulate in-situ infiltration
      in nine different soil types. The Osborne-More modified version of the Levenberg
      Marquardt optimization algorithm was coupled with the experimental data obtained
      by the double ring infiltrometers and the infiltration equations, to estimate the
      model parameters. Comparison of the model outputs with the experimental data
      indicates that the models can successfully describe cumulative infiltration in
      different soil types. However, since Kostiakov's equation fails to accurately
      simulate the infiltration rate as time approaches infinity, Philip's two-term
      equation, in some cases, produces negative values for the saturated hydraulic
      conductivity of soils, and the Green-Ampt model uses piston flow assumptions, we
      suggest using Philip's three-term equation to simulate infiltration and to
      estimate the saturated hydraulic conductivity of soils.

PMID- 17558779
TI  - Sorption kinetics of arsenic on laterite soil in aqueous medium.
AB  - The efficiency of a locally available laterite soil in removing both arsenite and
      arsenate from aqueous medium by adsorption was evaluated. It was observed that in
      batch experiment conducted at 0.5 mg/L initial concentration of arsenic, laterite
      soil could remove up to 98% of arsenite and 95% of arsenate under optimized
      conditions. The kinetic profiles under various conditions were developed. Both
      arsenite and arsenate removal followed pseudo--second order reaction kinetic
      model. Pore and film diffusion coefficients were determined from the half-time
      equation and film diffusion appeared to be the rate-limiting. This was further
      supported by multiple interruption tests.

PMID- 17558780
TI  - Review of kinetics of chemical and photocatalytical oxidation of Arsenic(III) as
      influenced by pH.
AB  - The kinetics and stoichiometry of As(III) oxidation by chemical oxidants is
      presented. The reactions are first-order with respect to each reactant. The
      second-order rate constants vary with pH and have a range in magnitude of 10(4)
      10(7) M-1 s-1 for free available chlorine (FAC), O3, and FeO4(2-) in a pH range
      of 6.0-9.0. In this pH range, the reactions of As(III) with chloroamine (NH2Cl)
      and H2O2 are quite slow with rate constants of 2.9-4.3x10(-1) M-1 s-1 and 2.6x10(
      2)-4.5x10(1) M-1 s-1 for chloroamine and H2O2, respectively. The pH dependence of
      the oxidation reactions can be described using acid-base equilibria of both
      As(III) species and the oxidant. FAC, O3, and FeO(4)2- oxidize As(III)
      instantaneously at pH 7.0 with half-lives of milliseconds if 2 mg/L excess dose
      of oxidant is applied. One major advantage of FeO4(2-) ions over the other
      oxidants is its ability to remove arsenic in water by two mechanisms; it oxidizes
      As(III) and also subsequently coagulates As(V) through Fe(III) hydroxide produced
      from Fe(VI) reduction. Photocatalytic oxidation of As(III) to As(V) follows zero
      order kinetics and the oxidation is completed in minutes with no significant pH
      dependence. The removal of dissolved arsenic to values below the World Health
      Organization drinking water limit of 10 microg/L can be achieved through
      photocatalytic oxidation of As(III) to As(V) in acidic solution followed by
      adsorption of As(V) onto TiO2 surfaces.

PMID- 17558781
TI  - Effect of the mixed liquor suspended solid on permeate in a membrane bioreactor
      system applied for the treatment of sewage mixed with wastewater of the milk from
      the dairy industry.
AB  - The performance of a bench-scale submerged membrane bioreactor (MBR) equipped
      with ultrafiltration membranes (ZENON) was investigated at different mixed liquor
      suspended solid (MLSS) concentrations (3069, 4314 and 6204 mg/L). The pilot plant
      was located in the wastewater treatment plant of the city of Granada (Puente de
      los Vados, Granada, Spain), which receives the wastewater of the milk from the
      dairy industry of Granada. The results showed the capacity of the MBR systems to
      remove organic material (COD and BOD5), suspended solids, turbidity, color and
      microbial indicators such as E. coli and coliphages. Therefore, the results
      suggest that the transmembrane pressure (TMP) was influence by the MLSS
      concentration assayed. However, an increase in the MLSS concentration increases
      the nitrification processes and consequently the amount of NO3- in permeate.

PMID- 17558782
TI  - Performance of vegetated and non-vegetated vertical flow reed beds in the
      treatment of diluted leachate.
AB  - This study was undertaken to investigate the behaviour of a vertical flow reed
      bed system with 3 kind of wastewaters (W1, W2 and W3) and for two hydraulic
      retention times (3 and 7 days) as well as to assess the role of Phragmites
      Australis in constructed wetland treatment processes. The adopted batch
      experimental system consisted of six vertical flow filters, filled with granular
      media and planted with reeds. For each vegetated reactor there was a
      correspondent blank in order to make a comparison. Wastewaters were obtained
      mixing tap water, MSW landfill leachate and activated sludge in different
      percentages. W1, W2 and W3 were designed in order to reproduce treated or
      untreated wastewaters not in compliance with legislation in force (Directive
      91/271/EEC), with increasing level of NH4+-N from W1 (16.3 mg/L) to W3 (76.0
      mg/L). In average terms, 3 days was sufficient for W1 and W2 to face the
      compliance limits; while, for W3 even 7 days was not sufficient to respect the
      compliance limit for ammonia nitrogen (1.4 times greater). The obtained results
      shown that the vegetation played an essential role especially in the removal of
      nitrogen: for the wastewater with the highest loads the contribution of reeds in
      the removal of nitrogen was greater than that of biofiltration processes. The
      contribution of the vegetation was also detectable in the removal of
      orthophosphate, but with minus efficiency.

PMID- 17558783
TI  - Colorectal cancer epigenetics: the role of environmental factors and the search
      for molecular biomarkers.
AB  - This review presents an evenhanded evaluation of the role of epigenetics in the
      development of colorectal cancer, and investigates the extent of environmental
      influences on modulating this disease. Advances in our understanding of chromatin
      structure, histone modification, transcriptional activity and DNA methylation
      have lead to an integrated approach to the role of epigenetics in carcinogenesis.
      Epigenetic mechanisms appear to permit response of individuals to environment
      through change in gene expression and are involved in inactivating one of the two
      X chromosomes in women. Epigenetic changes play an important role in development
      and can also arise stochastically as individuals age. Because epigenetic
      alterations are potentially reversible, thereby allowing malignant cells to
      revert to the normal state, there is potential to develop effective strategies to
      prevent or even reverse this curable cancer. Moreover, because the methylation
      status of a specific sequence or the pattern of methylation across the genome can
      now be measured accurately, molecular biomarkers of screening, diagnosis,
      prognosis, prediction of treatment and those related to risk assessment can be
      developed using sophisticated molecular genetic technologies. Although in many
      cases a high sensitivity and specificity of the detection assays has been
      achieved, there still remains ample room for improvement in areas of sample
      preparation, assay design and marker selection.

PMID- 17558784
TI  - Framework analysis for the carcinogenic mode of action of nitrobenzene.
AB  - Nitrobenzene (CASRN: 98-95-3) has been shown to induce cancers in many tissues
      including kidney, liver, and thyroid, following chronic inhalation in animals.
      However, with a few exceptions, genotoxicity assays using nitrobenzene have given
      negative results. Some DNA binding/adduct studies have brought forth questionable
      results and, considering the available weight of evidence, it does not appear
      that nitrobenzene causes cancer via a genotoxic mode of action. Nitrobenzene
      produces a number of free radicals during its reductive metabolism, in the gut as
      well as at the cellular level, and generates superoxide anion as a by-product
      during oxidative melabolism. The reactive species generated during nitrobenzene
      metabolism are considered candidates for carcinogenicity. Furthermore, several
      lines of evidence suggest that nitrobenzene exerts its carcinogenicity through a
      non-DNA reactive (epigenetic) fashion, such as a strong temporal relationship
      between non-, pre-, and neoplastic lesions leading to carcinogenesis. In this
      report, we first describe the absorption, distribution, metabolism, and excretion
      of nitrobenzene followed by a summary of the available genotoxicity studies and
      the only available cancer bioassay. We subsequently refer to the mode of action
      framework of the U.S. Environmental Protection Agency's 2005 Guidelines for
      Carcinogen Risk Assessment as a basis for presenting possible modes of action for
      nitrobenzene-induced cancers of the liver, thyroid, and kidney, as supported by
      the available experimental data. The rationale(s) regarding human relevance of
      each mode of action is also presented. Finally, we hypothesize that the
      carcinogenic mode of action for nitrobenzene is multifactorial in nature and
      reflective of free radicals, inflammation, and/or altered methylation.

PMID- 17558785
TI  - Public-private partnerships for health.

PMID- 17558786
TI  - Health communication in multilingual contexts: a study of reading preferences,
      practices, and proficiencies among literate adults in Zambia.
AB  - Comprehension of health materials and messages is a necessary, though not
      sufficient, condition for the development of health literacy; in the case of
      print materials, reading comprehension is elemental. Assessments of the
      population's ability to read and comprehend written materials are complex and
      highly salient in multilingual countries, such as Zambia, particularly when an
      excolonial language is but one of multiple official languages. Yet no study has
      contrasted adult Zambians' reading comprehension of health materials in the major
      Zambian languages with comparable English-language materials. This article
      reports the results of a survey of 2,009 literate Zambian adults who were tested
      for reading comprehension of health materials written at fourth- and eighth-grade
      levels. The analysis found that respondents who had not gone beyond primary
      school scored significantly higher on Zambian- than on English-language reading
      comprehension tests. Respondents with at least an eighth-grade education scored
      equally well or better on English-language compared with Zambian-language tests.
      Overall, respondents were more likely to pass the grade-four than the grade-eight
      reading comprehension tests. In the multilingual context of Zambia it is vital to
      produce health communication print materials written at or near a grade-four
      readability level in English and, when warranted, in appropriate Zambian
      languages.

PMID- 17558787
TI  - Consent and counter-mobilization: the case of the national smokers alliance.
AB  - Throughout the 1990s, health advocates engaged in a significant mobilization
      against the dangers of tobacco use and the tobacco industry. In 1993, the tobacco
      industry counter-mobilized through the National Smokers Alliance (NSA), a public
      relations created front group funded by the tobacco industry, which operated
      nationally from 1994 to 1999 to advocate for adults using tobacco products
      without vigorous regulation or increased tobacco taxes. The mobilization by
      health groups utilized traditional political lobbying and education of the public
      and public officials without a national public relations created front group to
      mold public opinion. The counter-mobilization by the NSA was based on traditional
      lobbying approaches in conjunction with the use of the public relations oriented
      consent engineering theory of Edward Bernays, Harold Lasswell, and others. This
      consent engineering theory calls for public relations specialists using public
      relations to mold public opinion to support a client's preferred public policy
      outputs. Despite the use of traditional lobbying in conjunction with the use of
      public relations efforts, attempts by the NSA to dominate public policy to weaken
      or neutralize stronger tobacco regulations and taxes were effective only for some
      campaigns.

PMID- 17558788
TI  - Talking about obesity: news framing of who is responsible for causing and fixing
      the problem.
AB  - Analyzing newspaper articles and television news, we explore how American news
      media have framed the issue of obesity. More specifically, we analyze the way the
      media present the question of who is responsible for causing and fixing the
      problem. Our data reveal that over the last 10 years, mentions of personal causes
      and solutions significantly have outnumbered societal attributions of
      responsibility. Recently, however, a balance was established between
      individualistic and societal attributions of responsibility. Mentions of societal
      causes and solutions have increased considerably, whereas decreasing numbers of
      personal solutions have appeared in the media. Findings also indicate that
      television news is more likely than newspapers to mention personal solutions, but
      less likely to attribute the responsibility to society.

PMID- 17558789
TI  - Thinking about "Think Again" in Canada: assessing a social marketing HIV/AIDS
      prevention campaign.
AB  - The Canadian "Think Again" social marketing HIV/AIDS prevention campaign, adapted
      from an American effort, encourages gay men to rethink their assumptions about
      their partners' HIV statuses and the risks of unsafe sex with them. To improve
      future efforts, existing HIV/AIDS prevention initiatives require critical
      reflection. While a formal evaluation of this campaign has been carried out
      elsewhere, here we use the campaign as a social marketing case study to
      illustrate its strengths and weaknesses, as a learning tool for other campaigns.
      After describing the campaign and its key results, we assess how it utilized
      central tenets of the social marketing process, such as formative research and
      the marketing mix. We then speak to the importance of theoretical influence in
      campaign design and the need to account for social-contextual factors in safer
      sex decision making. We conclude with a summary of the lessons learned from the
      assessment of this campaign.

PMID- 17558790
TI  - A classroom-administered simulation of a television campaign on adolescent
      smoking: testing an activation model of information exposure.
AB  - In recent years, research has shown that mass media can be used effectively
      either alone or in conjunction with interpersonal and institutional channels,
      such as schools. Much has yet been be learned about the application of newer,
      more effective strategies for media campaigns for adolescent smoking prevention
      interventions. This article describes a study applying an activation model of
      information exposure and a sensation-seeking targeting approach to the design of
      a smoking prevention campaign for adolescents. The participants were 1,272 middle
      school students aged 12-14 from across the Colorado Front Range who were
      stratified by their level of sensation seeking and then exposed to both high and
      low sensation value anti tobacco public service announcements (PSAs) at three
      time points. Hypothesized effects of the intervention on the primary dependent
      measures--attitudes (against smoking) and behavioral intentions not to smoke-
      were strongly supported for high sensation seekers. Further support is offered
      from the secondary indicators, self-efficacy, perceived message effectiveness,
      and perceived risk from smoking. No differences were demonstrated, however, in
      message effects between those selected by focus groups to be high in sensation
      value and those selected to be low in sensation value.

PMID- 17558792
TI  - Biopolitics at the bedside. Proxy wars and feeding tubes.

PMID- 17558793
TI  - Legal and ethical issues in heroin diagnosis, treatment, and research.

PMID- 17558794
TI  - Medical tourism. Concerns, benefits, and the American legal perspective.

PMID- 17558795
TI  - The demise of medical malpractice screening panels and alternative solutions
      based on trust and honesty.

PMID- 17558796
TI  - Unsound ultrasounds? An examination of state legislation regulating non-medical
      ultrasound use and private ownership.

PMID- 17558800
TI  - Survey of current lead use, handling, hygiene, and contaminant controls among New
      Jersey industries.
AB  - In 2003, a chemical handling and use survey was mailed to New Jersey employers
      identified as currently using lead in their industrial processes. This survey was
      used to ascertain characteristics about lead use, handling, and protection of
      employees during manufacturing operations. The survey included a diverse group of
      current lead users with a total lead use range from less than 1 pound to more
      than 63 million pounds of lead per year. The survey allowed for a comprehensive
      characterization of hazards and protective measures associated with this metal,
      still commonly used in many products and industrial processes. Forty-five surveys
      were returned by companies that are listed in the New Jersey Adult Blood Lead
      Registry, which is part of the New Jersey Adult Blood Lead Epidemiology and
      Surveillance (ABLES) program. This program records and investigates cases of
      adults with greater than 25 mu g/dL of lead in their blood; most cases are
      related to occupational exposures. This survey found that greater than 25% of
      these surveyed companies with significant potential for lead exposure did not
      employ commonly used and basic industrial hygiene practices. In addition, the
      survey found that 24% of these companies had not conducted air sampling within
      the last 3 years. Air sampling is the primary trigger for compliance with the
      Occupational Safety and Health Administration (OSHA) general industry lead
      standard. Only 17% of the companies have ever been cited for a violation of the
      OSHA lead standard, and only 46% of these companies have ever had an OSHA
      inspection. State-based surveillance can be a useful tool for OSHA enforcement
      activities. Elevated blood lead values in adults should be considered as a
      trigger for required compliance with an OSHA general industry lead standard.

PMID- 17558801
TI  - Airborne concentrations of benzene associated with the historical use of some
      formulations of liquid wrench.
AB  - The current study characterizes potential inhalation exposures to benzene
      associated with the historical use of some formulations of Liquid Wrench under
      specific test conditions. This product is a multiuse penetrant and lubricant
      commonly used in a variety of consumer and industrial settings. The study
      entailed the remanufacturing of several product formulations to have similar
      physical and chemical properties to most nonaerosol Liquid Wrench formulations
      between 1960 and 1978. The airborne concentrations of benzene and other
      constituents during the simulated application of these products were measured
      under a range of conditions. Nearly 200 breathing zone and area bystander air
      samples were collected during 11 different product use scenarios. Depending on
      the tests performed, average airborne concentrations of benzene ranged from
      approximately 0.2-9.9 mg/m(3) (0.08-3.8 ppm) for the 15-min personal samples; 0.1
      8 mg/m(3) (0.04-3 ppm) for the 1-hr personal samples; and 0.1-5.1 mg/m(3) (0.04-2
      ppm) for the 1-hr area samples. The 1-hr personal samples encompassed two 15-min
      product applications and two 15-min periods of standing within 5 to 10 feet of
      the work area. The measured airborne concentrations of benzene varied
      significantly based on the benzene content of the formulation tested (1%, 3%,
      14%, or 30% v/v benzene) and the indoor air exchange rate but did not vary much
      with the base formulation of the product or the two quantities of Liquid Wrench
      used. The airborne concentrations of five other volatile chemicals (ethylbenzene,
      toluene, total xylenes, cyclohexane, and hexane) were also measured, and the
      results were consistent with the volatility and concentrations of these chemicals
      in the product tested. A linear regression analysis of air concentration compared
      with the chemical mole fraction in the solution and air exchange rate provided a
      relatively good fit to the data. The results of this study should be useful for
      evaluating potential inhalation exposures to benzene and other volatile chemicals
      that occurred during the past use of some formulations of Liquid Wrench and
      perhaps for some similar products containing these chemicals.

PMID- 17558802
TI  - Review of chamber design requirements for testing of personal protective clothing
      ensembles.
AB  - This review focuses on the physical requirements for conducting ensemble testing
      and describes the salient issues that organizations involved in the design, test,
      or certification of personal protective equipment (PPE) and protective clothing
      ensembles need to consider for strategic planning. Several current and proposed
      PPE ensemble test practices and standards were identified. The man-in-simulant
      test (MIST) is the primary procedure used by the military to evaluate clothing
      ensembles for protection against chemical and biological warfare agents. MIST has
      been incorporated into the current editions of protective clothing and equipment
      standards promulgated by the National Fire Protection Association (NFPA). ASTM
      has recently developed a new test method (ASTM F 2588-06) for MIST evaluation of
      protective ensembles. Other relevant test methods include those described in
      International Organization for Standardization (ISO) standards. The primary
      differences among the test methods were the choice of test challenge material
      (e.g., sulfur hexafluoride, methyl salicylate, sodium chloride particles, corn
      oil, fluorophore-impregnated silica) and the exercise protocol for the
      subject(s). Although ensemble test methods and standards provide detailed
      descriptions of the test procedures, none give specific requirements for chamber
      design. A literature survey identified 28 whole-body exposure chambers that have
      been or could potentially be used for testing protective clothing ensembles using
      human test subjects. Median chamber size, median floor space, and median volume
      per subject were calculated from 15 chambers (involving human test subjects),
      where size information is available. Based on the literature survey of existing
      chambers and the review of the current and proposed standards and test methods,
      chamber design requirements will be dictated by the test methods selected. Due to
      widely different test conditions for aerosol/particulate and vapor ensemble
      testing, it is unlikely that a single chamber could accommodate all types of
      ensemble testing. With increasing use of the MIST protocol by NFPA for CBRN
      certification of structural firefighting gear and protective ensembles for first
      responders, the need for MIST laboratory capability is clear. However, existing
      chambers can likely be adapted to accommodate MIST with some modifications.

PMID- 17558803
TI  - Formaldehyde-protein conjugate-specific antibodies in rats exposed to
      formaldehyde.
AB  - A large human population is exposed to formaldehyde (FA) environmentally and
      occupationally, leading to a variety of respiratory and dermatological
      disturbances. FA covalently binds with proteins to form FA-protein conjugates,
      which might lead to the formation of FA-specific antibodies. The focus of this
      investigation was to study the formation of antibodies against FA-protein
      conjugates in rats for their possible use as biological markers of FA exposure.
      Male Sprague-Dawley rats were fed FA via drinking water (1.6 mg/ml) for up to 6
      mo. Blood was collected at 3 and 6 mo following FA exposure, and formation of
      anti-FA-albumin adduct (anti-FAA) antibodies measured in the serum samples (1:100
      dilution) by an enzyme-linked immunosorbent assay (ELISA) using synthesized rat
      albumin conjugates of FA as the solid-phase antigen. Sera from FA-treated rats
      showed induction of antibodies to FAA in 50% of the animals at both 3 and 6 mo,
      and the antibody titer was higher at 6 mo, suggesting a greater antibody response
      with exposure period. These antibodies were highly specific for FAA as they did
      not cross-react with malondialdehyde-, 4-hydroxynonenal-, 4-hydroxyhexenal-, and
      acrolein-albumin adducts. The specificity of anti-FAA antibodies was further
      evaluated by inhibition studies that showed a dose-dependent decrease in binding
      when the serum was preincubated with increasing concentrations of FAA, and by
      Western blot analysis that showed immunoreactivity of the antibody with FAA but
      not with rat albumin. Furthermore, the anti-FAA antibodies (rat serum) also
      recognized FA-human albumin (FAHA) conjugates, but had only approximately one
      third of the binding affinity in comparison to FAA. Induction of anti-FA-protein
      conjugate antibodies could be further evaluated to serve as a biomarker of FA
      exposure.

PMID- 17558804
TI  - Retrospective exposure assessment of airborne asbestos related to skilled
      craftsmen at a petroleum refinery in Beaumont, Texas (1940-2006).
AB  - Despite efforts over the past 50 or more years to estimate airborne dust or fiber
      concentrations for specific job tasks within different industries, there have
      been no known attempts to reconstruct historical asbestos exposures for the many
      types of trades employed in various nonmanufacturing settings. In this paper, 8-h
      time-weighted average (TWA) asbestos exposures were estimated for 12 different
      crafts from the 1940s to the present day at a large petroleum refinery in
      Beaumont, TX. The crafts evaluated were insulators, pipefitters, boilermakers,
      masons, welders, sheet-metal workers, millwrights, electricians, carpenters,
      painters, laborers, and maintenance workers. This analysis quantitatively
      accounts for (1) the historical use of asbestos-containing materials at the
      refinery, (2) the typical workday of the different crafts and specific
      opportunities for exposure to asbestos, (3) industrial hygiene asbestos air
      monitoring data collected at this refinery and similar facilities since the early
      1970s, (4) published and unpublished data sets on task-specific dust or fiber
      concentrations encountered in various industrial settings since the late 1930s,
      and (5) the evolution of respirator use and other workplace practices that
      occurred as the hazards of asbestos became better understood over time. Due to
      limited air monitoring data for most crafts, 8-h TWA fiber concentrations were
      calculated only for insulators, while all other crafts were estimated to have
      experienced 8-h TWA fiber concentrations at some fraction of that experienced by
      insulators. A probabilistic (Monte Carlo) model was used to account for potential
      variability in the various data sets and the uncertainty in our knowledge of
      selected input parameters used to estimate exposure. Significant reliance was
      also placed on our collective professional experiences working in the fields of
      industrial hygiene, exposure assessment, and process engineering over the last 40
      yr. Insulators at this refinery were estimated to have experienced 50th (and
      95th) percentile 8-h TWA asbestos exposures (which incorporated 8-h TWA fiber
      concentrations, respirator use and effectiveness, and time spent working with
      asbestos-containing materials) of 9 (16) fibers/cc (cubic centimeter) from 1940
      to 1950, 8 (13) fibers/cc from 1951 to 1965, 2 (5) fibers/cc from 1966 to 1971,
      0.3 (0.5) fibers/cc from 1972 to 1975, and 0.005 (0.02) fibers/cc from 1976 to
      1985 (estimated exposures were <0.001 fibers/cc after 1985). Estimated 8-h TWA
      exposures for all other crafts were at least 50- to 100-fold less than that of
      insulators, with the exception of laborers, whose estimated 8-h TWA exposures
      were approximately one-fifth to one-tenth of those of insulators. In spite of the
      data gaps, the available evidence indicates that our estimates of 8-h TWA
      asbestos exposures reasonably characterize the typical range of values for these
      categories of workers over time.

PMID- 17558805
TI  - Effects of polycyclic aromatic hydrocarbon-containing oil mixtures on generation
      of reactive oxygen species and cell viability in MCF-7 breast cancer cells.
AB  - Clarified slurry oil (CSO), and two crude oil samples, Belridge heavy crude oil
      (BHCO) and Lost Hills light crude oil (LHLCO), were examined for their ability to
      generate reactive oxygen species (ROS) in MCF-7 cells. Intracellular ROS and cell
      viability were determined in a flow cytometer using dihydroxyrhodamine 123 and
      propidium iodide, respectively. In experiments with short-term exposure, single
      cell suspensions were loaded with the fluorescent probes and then treated with
      the oil samples (1 or 10 ppm). Measurements were made at 5, 15, 30, 60, and 90
      min after addition of oil samples. In experiments with longer term exposure,
      preconfluent cell cultures were treated with oil samples for 6, 12, or 24 h prior
      to preparing single-cell suspensions. Both short-term and longer term treatment
      with oil samples resulted in elevated generation of reactive oxygen species
      (ROS). Cell cultures also were treated with benzo[a]pyrene, a polycyclic aromatic
      hydrocarbon detected in all three oil samples. Treatment with benzo[a]pyrene
      produced a significant increase in levels of ROS. The present findings suggest
      that oil samples with higher concentrations of polycyclic aromatic hydrocarbons
      may exert adverse effects on human mammary epithelial tissue through induction of
      oxidative stress.

PMID- 17558806
TI  - A comparison of the pulmonary inflammatory potential of different components of
      yeast cell wall.
AB  - 1-->3-Beta-glucan has been associated with pulmonary inflammation induced by
      exposure to fungal or yeast cell wall dust. 1-->3-Beta-glucan is the major cell
      wall component of yeast or fungi. However, the yeast cell wall contains several
      other components besides 1-->3-beta-glucans, such as mannan and chitin. Few
      studies evaluated the contribution of these other cell wall components to
      pulmonary inflammation. The present study compares a crude particulate yeast cell
      wall preparation (zymosan A) to purified yeast glucan, purified yeast glucan
      mannan, or purified yeast glucan chitin particles for their potency to induce
      mouse pulmonary inflammation after in vivo exposure. Mannan is the second most
      abundant polysaccharide in the yeast cell wall, whereas chitin content is a minor
      component. The results show that pulmonary injury is mediated by both chitin and
      1-->3-beta-glucan and to a lesser degree by mannan. There is also evidence that
      zymosan is more potent than purified 1-->3-beta-glucan alone. Evidence indicates
      that 1-->3-beta-glucan is the major inflammatory component in yeast and fungal
      cell walls.

PMID- 17558807
TI  - Frequency of paraoxonase 192/55 polymorphism in an Iranian population.
AB  - Paraoxonase (PON1) is a serum enzyme that plays an important role in prevention
      of atherosclerosis and also protects against organophosphate-induced
      neurotoxicity. PON1 displays a high variability in human populations. In this
      study, PON1-192 and -55 polymorphisms and correlation to serum PON1 activity were
      investigated in 132 healthy Iranian individuals from Isfahan province. The
      genotype frequencies for PON1-192 were approximately 48% (QQ), 42.% (QR), and 10%
      (RR) and for PON1-55 17% (MM), 48% (ML), and 35% (LL). Thus, the frequencies of
      alleles R and L were 0.31 and 0.59, respectively. PON1 activity toward paraoxon
      was markedly affected in both polymorphic populations in the following order QQ <
      QR < RR genotype for PON1-192 and MM < ML < LL genotype for PON1-55. Neither
      polymorphism significantly affected PON1 activity toward phenylacetate. The RR/LL
      individuals had the highest PON1 activity and QQ/MM individuals the least. The
      QR/ML haplotype was the most frequent seen in Iranians, and the RR/MM and QR/MM
      haplotypes were absent in this population. In conclusion, the frequencies of PON1
      192 and -55 polymorphisms in this Iranian population were different from those
      seen in other Asian populations from Japan and China but similar to those for
      European Caucasians.

PMID- 17558808
TI  - Suppression of humoral immunity following exposure to the perfluorinated
      insecticide sulfluramid.
AB  - Perfluorinated hydrocarbons have been manufactured for over 40 yr and have
      numerous applications in industry. This group of compounds has recently generated
      much interest, as some of these compounds such as perfluorooctane sulfonate
      (PFOS) and perfluoroctanic acid (PFOA) are persistent in the environment and
      detectable in blood samples of both wildlife and humans. Studies show that these
      perfluorinated compounds induce peroxisomal proliferation, induce hepatomegaly,
      alter steroidogenesis, and decrease body weight, accompanied by a wasting
      syndrome; however, effects on immune function have not been addressed at length.
      This study examined sulfluramid, a perfluorinated pesticide that is currently
      available in the marketplace and is a representative member of this class of
      chemicals. Adult female B6C3F1 mice were exposed via gavage to either an oil
      carrier control or sulfluramid for 14 d (1, 3, 10, or 30 mg/kg/d) or 28 d (0.3,
      1, 3, or 10 mg/kg/d). Although responses were normal in natural killer cell
      activity and lymphocyte proliferation, dose-responsive suppression was noted in
      the plaque forming cell (PFC) response at exposure levels as low as 3 mg/kg/d in
      the 14-d exposure and 0.3 mg/kg/d for 28 d. Dose-responsive increases in liver
      mass were observed following treatment with 1, 3, 10, or 30 mg/kg/d for 14 d and
      0.3, 1, 3, or 10 mg/kg/d for 28 d. A significant reduction in body weight was
      observed at the highest dose level in each study. Novel findings in this study
      indicate that sulfluramid suppresses immunoglobulin (Ig) M production. Additional
      immunotoxicity studies are required to understand potential mechanisms of
      suppression and determine potential health risks associated with exposure to
      perfluorinated hydrocarbons.

PMID- 17558809
TI  - Perchlorate inhibition of iodide uptake in normal and iodine-deficient rats.
AB  - Perchlorate-induced inhibition of thyroidal iodide uptake was measured in normal
      and iodine-deficient female Sprague-Dawley rats. Rats that were made iodine
      deficient by long-term restriction of iodine in the diet absorbed a gavage dose
      of 131I to the thyroid in proportionally greater amounts than rats fed a normal
      diet. Furthermore, the iodine-deficient rats maintained their high rates of
      absorption even when challenged by levels of perchlorate in their drinking water
      sufficient to produce pronounced inhibition of 131I uptake in rats fed a normal
      diet. Every dose of perchlorate used in this study (1.1, 5.6, and 28 mg/L)
      produced significant inhibition of iodide uptake in normally fed rats, but only
      the highest level of perchlorate (28 mg/L) significantly inhibited thyroidal
      uptake of 131I in the iodine-deficient rats. Taken together, these results
      demonstrate that iodide-deficient animals exhibit increased resistance to the
      inhibition of iodine absorption resulting from perchlorate exposure.

PMID- 17558810
TI  - Gene expression changes and induction of cell proliferation by chronic exposure
      to arsenic of mouse testicular Leydig cells.
AB  - Arsenic is an important environmental carcinogen that affects millions of people
      worldwide through contaminated water supplies. Chronic exposure of arsenic has
      been shown to induce malignant transformation of mammalian cells; however, the
      mechanism underlying arsenic-induced carcinogenesis is not clear. The (1)
      induction in the cell proliferation, (2) decrease in DNA repair capacity
      resulting in the accumulation of mutations, and (3) changes in the DNA
      methylation patterns affecting regulation of genes are hallmarks of cancer
      development. Thus, the purpose of this study was to determine whether long-term
      exposure of both low and high concentrations of arsenic can perturb cell
      proliferation, DNA repair, and the maintenance of DNA methylation status in TM3
      cells, an immortalized Leydig cell derived from normal mouse testis. The effect
      of arsenic on cell proliferation was determined by cell count data, and arsenic
      induced gene expression changes were measured by quantitative real-time
      polymerase chain reduction (PCR). The results this study revealed a concentration
      dependent induction of cell proliferation by arsenic. Increased expression of
      cell proliferation marker genes (PCNA, CyclinD1) and DNA methylation (DNA Methyl
      Transferase I) and decreased expression of genes for DNA repair (DNA Polymerase
      beta, ERCC6) with lower concentrations of arsenic was also observed. Thus, the
      findings of this study are novel, as they indicate a mechanism for arsenic
      induced cancers. This is based on the observed increase in cell proliferation and
      decrease in the capacity of cells to maintain its genomic stability. Our study
      provides the evidence that arsenic may play a role in the etiology of testicular
      cancer.

PMID- 17558811
TI  - Rhapontigenin from Rheum undulatum protects against oxidative-stress-induced cell
      damage through antioxidant activity.
AB  - The antioxidant properties of rhapontigenin and rhaponticin isolated from Rheum
      undulatum were investigated. Rhapontigenin was found to scavenge intracellular
      reactive oxygen species (ROS), the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical,
      and hydrogen peroxide (H2O2). The radical scavenging effect of rhapontigenin was
      more effective than rhaponticin. Rhapontigenin protected against H2O2-induced
      membrane lipid peroxidation and cellular DNA damage, which are the main targets
      of oxidative stress-induced cellular damage. The radical scavenging activity of
      rhapontigenin protected Chinese hamster lung fibroblast (V79-4) cells exposed to
      H2O2 by inhibiting apoptosis. Rhapontigenin inhibited cell damage induced by
      serum starvation and was also found to increase the activity of catalase and its
      protein expression. Further, rhapontigenin increased phosphorylation of
      extracellular signal-regulated kinase (ERK) and inhibited the activity of
      activator protein 1 (AP-1), a redox-sensitive transcription factor. In summary,
      these results suggest that rhapontigenin protects V79-4 cells against oxidative
      damage by enhancing the cellular antioxidant activity and modulating cellular
      signal pathways.

PMID- 17558812
TI  - Direction of hair whorl and handedness.
AB  - We recorded the direction of hair whorl rotation in samples of male right- and
      non-right-handers. The data corroborate those of Klar (2003) in showing equal
      numbers of clockwise and anti-clockwise whorls in non-right-handers but an excess
      of clockwise whorls in right-handers. The findings support the view that in some
      proportion of the population direction of coiling arises as a consequence of
      random events occurring during early (pre-natal) development of the nervous
      system, while in the remainder of the population there is a systematic bias
      towards a clockwise direction of rotation. The association with handedness
      implies that the latter is in a very large measure biologically rather than
      culturally determined.

PMID- 17558813
TI  - Lifespan trends of side bias in India.
AB  - This study examines the (a) lifespan trends, (b) theoretical propositions, (c)
      factor structure, and (d) congruency among different forms of side bias in an
      Indian sample (N=3474) using the preference measure of handedness, footedness,
      eyedness, and earedness. An increase in dextral preference was found in all
      indices of side bias with increasing age. There were no left-handers among the
      oldest adults. This trend was not found for footedness, eyedness, and earedness.
      Females were more right sided than males on all indices of side bias except
      handedness. The preferential use of limbs stabilised during young adulthood but
      eye and ear preference did not. Three factors were underlying the formation and
      maintenance of four forms of side bias. Handedness and footedness constituted one
      factor, and eyedness and earedness were independent separate factors. The first
      two had highest association and the last two had lowest congruency.

PMID- 17558814
TI  - Asymmetry of visually guided sexual behaviour in adult Japanese quail (Coturnix
      japonica).
AB  - Sexually active adult Japanese quail (Coturnix coturnix japonica) were trained to
      run across either a left- or a right-turning runway to obtain sexual access to a
      conspecific of the opposite sex. The birds tested with only their right eye in
      use showed significantly higher latencies to complete the runway task than the
      birds tested binocularly and those using the left eye. In all of the three
      experimental conditions, male birds were significantly faster than their female
      counterparts. Generally, these findings are compatible with previous evidence for
      lateralisation in sexually motivated behaviour in birds. However, unlike the
      previous findings that suggested a loss of lateralisation in pattern
      discrimination in quail during adulthood, the present study shows that
      asymmetries in visually guided sexual behaviour persist in adult quail. Thus, our
      study implies that ontogenetic and lateralised changes within the visual system
      can be differently organised for different output pathways.

PMID- 17558815
TI  - Phonological and semantic processing of words: laterality changes according to
      gender in right- and left-handers.
AB  - The ability of cerebral hemispheres to process language is influenced by multiple
      factors. The well-known right visual field advantage in word recognition in
      divided visual field tasks is affected by both intra- and inter-individual
      variables. For example, hemispheric linguistic abilities may vary within a given
      individual according to the language component being processed, whereas
      variations between individuals may be modulated by the individual's handedness
      and gender. The objective of this divided visual field study was to compare
      gender differences in right- and left-handers in relation to their hemispheric
      abilities in performing phonological and semantic tasks. The results indicate
      that for both types of processing, gender had a different impact on right- and
      left-handed groups. Unexpectedly, a gender difference in laterality pattern was
      found in left-handers but not in right-handers for both phonological and semantic
      abilities. Intriguingly, left-handed men displayed a more symmetrical laterality
      pattern in phonological and semantic abilities than left-handed women.

PMID- 17558816
TI  - Visual bisection of freely-viewed asymmetrical stimuli.
AB  - When performing line bisection tasks, neurologically normal individuals exhibit
      leftward biases. Similarly, normals also exhibit leftward biases during
      judgements of brightness, numerosity, and size. However, when these same
      judgement stimuli are visually bisected, this results in rightward bisection
      biases. These apparently contradictory results are complicated by the fact that
      bisection tasks are typically performed using single stimuli, whereas judgements
      of brightness, numerosity, and size are performed on pairs of stimuli. The
      present study examined the effects of visual bisection on pairs of stimuli. A
      sample of 34 undergraduate psychology volunteers exhibited leftward biases when
      making judgements of brightness, numerosity, and size. However, these same
      participants did not exhibit leftward bisection biases with the same stimuli.
      Instead, overall rightward bisection errors were observed. These results indicate
      that although these two types of tasks elicit similar perceptual biases, they are
      probably the result of different perceptual mechanisms.

PMID- 17558817
TI  - A longitudinal study on hand use while building a tower.
AB  - The aim of the study was to describe a developmental trend of hand use for
      picking up and stacking blocks from the age of 18 months to 7 years. A second aim
      was to determine whether there is a relationship between right-hand use while
      building a tower and manual laterality at school age. A total of 28 children were
      asked to build a tower at five longitudinal assessments. The use of the right
      hand fluctuated considerably with age (p<.05), but no age-related increase was
      observed. Right-hand use was rather prominent at 18 months, decreased
      significantly at 26 months, increased at age 4;7, decreased again at 5;7, and
      finally increased again at age 7. From age 4;7 onwards, the percentage of right
      hand use for stacking the blocks was significantly (p<.05) related to the
      laterality quotient at school age.

PMID- 17558818
TI  - Task demands affect manual asymmetries in pegboard performance.
AB  - Previous work by Bryden and Roy (1999) showed a larger performance difference
      between the hands for placing pegs into holes on the Grooved Pegboard test than
      for removing pegs from the holes. The authors argued that these data provided
      evidence of the importance of task demands in manual asymmetries. However the
      study failed to control for the differing starting positions of the pegs. To
      clarify this possible confound, the purpose of the current investigation was to
      determine the influence of starting position on the between-hand performance
      differences on the Grooved Pegboard Test. To do so, both the start and end
      positions were manipulated, such that participants moved the pegs from the
      receptacle to another receptacle or to a set of holes, or participants moved the
      pegs from a set of holes to a receptacle or another set of holes. A total of 30
      right-handed individuals (as classified using the Waterloo Handedness
      Questionnaire) participated in the experiment, completing five trials with each
      hand for each of the four conditions. While no significant effects of start
      position were found, a significant interaction between hand and end position,
      F(1.29) = 30.85, P<.001, was found for the time to complete the task, where
      larger differences between the hands, fovouring the right hand, were seen for
      placing pegs into the holes as opposed to the receptacles. This effect was also
      found when the data were expressed using a laterality quotient. The results are
      discussed in terms of the influence of task complexity on manual asymmetries.

PMID- 17558819
TI  - What's new in Nicotine & Tobacco Research?

PMID- 17558820
TI  - Is there a health benefit of reduced tobacco consumption? A systematic review.
AB  - This review presents the available evidence on the health effects of reduced
      smoking. Smoking reduction was defined as reduction of the daily intake of
      tobacco without quitting. Only published papers were reviewed. Case reports and
      studies without a thorough definition of smoking reduction or health outcome were
      excluded. We searched in personal databases, BioMail Medline Search, Medline, the
      Cochrane Database of Systematic Reviews, and EMBASE. We followed the QUORUM
      standards for systematic reviews, and both authors read and discussed all
      publications. A total of 25 studies (31 publications) were identified: 8 articles
      reported on effects on the cardiovascular system; 11 on the airways; 7 on
      carcinogens, DNA damage, and lung cancer; 3 on birth weight; and 4 on other
      health effects. Some papers assessed more than one outcome. In most studies,
      reduction was defined as less than 50% of baseline tobacco consumption. Most of
      the studies were small, with the populations selected and short follow-up
      periods. The limited data suggest that a substantial reduction in smoking
      improves several cardiovascular risk factors and respiratory symptoms. In
      addition, smoking reduction is associated with a 25% decline in biomarkers and
      incidence of lung cancer and a small, mostly nonsignificant, increase in birth
      weight. There seem to be no substantial beneficial effects on lung function. The
      evidence on other health effects and mortality is too limited to draw
      conclusions. A substantial reduction in smoking seems to have a small health
      benefit, but more studies are needed to determine the long-term effects of
      smoking reduction.

PMID- 17558821
TI  - Tobacco craving predicts lapse to smoking among adolescent smokers in cessation
      treatment.
AB  - Previous research indicates that tobacco craving predicts relapse to smoking
      among adult smokers attempting to quit. We hypothesized a similar relationship
      between craving and lapse (any smoking following a period of abstinence) among
      adolescent smokers during the treatment phase of a clinical trial. A visit was
      considered a lapse visit if the participant reported smoking or had a carbon
      monoxide level of 7 ppm or greater subsequent to an abstinent visit. A total of
      34 participants (mean age = 14.9 years [SD = 1.3]; mean cigarettes/day = 18.0 [SD
      = 7.6]; mean Fagerstrom Test for Nicotine Dependence score = 6.8 [SD = 1.34]; 65%
      female), were included in the present analysis of 167 treatment visits. Logistic
      regression analyses showed a positive relationship between degree of craving,
      measured by the Questionnaire on Smoking Urges, and lapse during smoking
      cessation treatment (p = .013). Additionally, linear regression analyses
      demonstrated a strong positive association between cigarettes smoked per day and
      craving scores (p<.001). Taken together with other data, these findings suggest
      that degree of craving might influence tobacco abstinence for adolescent smokers.
      Thus monitoring and addressing craving appears useful to increase the success of
      adolescent smoking cessation.

PMID- 17558822
TI  - Nurses' knowledge about the risk of light cigarettes and other tobacco "harm
      reduction" strategies.
AB  - Light and ultra-light cigarettes are associated with little or no risk reduction
      versus regular cigarettes, but the majority of smokers believe they are safer. We
      evaluated whether nurses believe that certain products (light and ultra-light
      cigarettes, reduced-tar cigarettes, nicotine replacement), cigarette design
      features (filters, no additives), and smoking behaviors (smoking reduction)
      reduce health risks among their patients. Nurses (N = 178; 93% female, 10%
      smokers) completed questionnaires before mandatory training in smoking cessation
      counseling. Among respondents, 25% believed that light and ultra-light cigarettes
      are equal in tar to regular cigarettes, 55% believed that two light cigarettes
      are equal in tar to one regular cigarette, and 51% believed that three or more
      ultra-light cigarettes are equal to one regular cigarette. Further, 40% believed
      that light and ultra-light cigarettes are less dangerous; younger nurses (<41
      years old) were more likely to believe this than older nurses (p<.05). A total of
      14% of nurses would recommend light and ultra-light cigarettes to help patients
      reduce health risks, 15% said that cigars are less harmful than cigarettes, 41%
      said that additive-free cigarettes are less dangerous, and 81% said that cutting
      down to 5 cigarettes/day improves health. Nurses had misperceptions about
      nicotine replacement: 60% believed that nicotine causes cancer, 72% believed that
      nicotine patches could cause heart attacks, and 40% and 15% believed that a
      prescription is needed for the nicotine patch or gum, respectively. Among nurses,
      smokers were more likely than nonsmokers to believe that smoking risks are
      exaggerated (p<.05). Nurse misinformation could lead to inaccurate
      recommendations and failure to capitalize on the teachable moment provided by the
      medical encounter.

PMID- 17558823
TI  - Staying smoke free: an intervention to prevent postpartum relapse.
AB  - This pilot study evaluated the effectiveness of a nurse-delivered home-visiting
      program during the postpartum period that included a low-intensity smoking
      relapse-prevention intervention. A prospective two-group design was used.
      Participants were women who had quit smoking during their pregnancy. They were
      invited to participate during postpartum hospitalization on a university hospital
      postpartum ward. A brief intervention during postpartum hospitalization, a home
      visit, and two follow-up phone calls over a 1- to 2-month period were compared
      with a routine home visit without any prescribed focus on tobacco use. The main
      outcome was biochemically verified smoking abstinence at 3 and 6 months
      postenrollment. Abstinence was defined as a salivary cotinine level of 14 ng/ml
      or less. At 3 months postenrollment, 26.4% of the intervention group were
      classified as abstinent, compared with 12.4% of the comparison group (OR = 2.4,
      95% CI = 1.16-4.98). At 6 months, the proportion of the intervention group
      categorized as abstinent was 21.5%, compared with 10.2% of comparison group
      participants (OR = 2.5, 95% CI = 1.13-5.71). Greater than three times as many in
      the intervention group remained abstinent at both times (18.2%), compared with
      the comparison group (5.2%; OR = 2.4, 95% CI = 1.16-4.93). The effectiveness of
      this brief, low-cost, and potentially replicable intervention in improving the
      rate of persistent postpartum smoke-free status for women who quit smoking during
      pregnancy is encouraging. A randomized trial of the approach is warranted.

PMID- 17558824
TI  - Interest in gradual cessation.
AB  - Prior surveys have not determined smokers' interest in gradual cessation. In
      Study 1A, we advertised in six U.S. east coast newspapers for "smokers who plan
      to quit smoking" to participate in a nontreatment study. Among the 461
      respondents, 66% planned to reduce and then stop smoking, 13% planned to stop
      abruptly, and 21% reported they planned to reduce but not quit. In Study 1B, we
      ran a similar ad but asked for "smokers who plan to reduce their smoking." Among
      the 263 respondents, 57% planned to reduce and then stop smoking and 33% planned
      to reduce but not stop smoking. In Study 2, we asked 125 smokers to rate their
      interest in quitting smoking (on a 1-10 scale) given two scenarios. When nicotine
      replacement therapy (NRT) was not mentioned, interest in gradual cessation was
      high and was higher than interest in abrupt cessation (6.9 and 4.7, respectively,
      p<.0001). When NRT was assumed to be available for gradual or abrupt cessation,
      interest in gradual cessation remained high (7.1) and was similar to that for
      abrupt cessation (7.0). In both scenarios, over three-fourths of smokers were at
      least as interested in gradual cessation as they were in abrupt cessation.

PMID- 17558825
TI  - Depression predicts smoking early but not late in a quit attempt.
AB  - This study examined the relationship between depression history and smoking after
      a quit attempt. A total of 677 smokers participating in a randomized smoking
      cessation trial (Smith et al., 2001) provided data on current depression,
      depression history, and depression-related measures and smoking at 1 week and 6
      months after a quit date. Depression history predicted smoking at 1 week postquit
      but not at 6 months postquit. Smoking during the first week was not predictive of
      smoking at 6 months in those with a history of depression but was predictive
      among those with no history of depression. Prediction models including depression
      history and depression-related measures (e.g., negative affect, negative
      cognitive style) showed that depression history was a powerful predictor of
      smoking early in the quit attempt.

PMID- 17558826
TI  - Cigarette smoking patterns among young adults aged 18-24 years in the United
      States.
AB  - Most tobacco control programs focus on prevention for children or cessation for
      adults. Little is known about cigarette smoking among young adults. This study
      examined sociodemographic variables associated with current, daily, heavy, and
      light smoking among young adults in the United States. Data from the 1998-1999
      Tobacco Use Supplement to the Current Population Survey (TUS-CPS) were used to
      examine cigarette smoking patterns and correlates of smoking among 15,371 young
      adults aged 18-24 years. We found that 26% of young adults were current smokers,
      20% were daily smokers, and 8% were former smokers. Current smoking rates were
      higher among American Indians/Alaska Natives (33%) and Whites (31%) than among
      other racial/ethnic groups. Compared with white-collar workers, blue-collar and
      service workers were more likely to report current and daily smoking. Blue-collar
      workers also were more likely to report heavy smoking (OR = 1.97). The unemployed
      (those in the labor force but not currently working) and those reporting an
      annual household income of less than US$20,000 were more likely to report
      current, daily, and heavy smoking, compared with those not in the labor force and
      those reporting an annual household income of $20,000 or more, respectively.
      Young adults not currently enrolled in school were more than twice as likely to
      report current (OR = 2.36) and daily (OR = 2.90) smoking, compared with those
      currently enrolled in school. Differential cigarette smoking patterns by
      race/ethnicity, occupation, employment status, household income, and school
      enrollment status should be considered when developing interventions to reduce
      smoking among young adults.

PMID- 17558827
TI  - Bupropion and cognitive-behavioral therapy for smoking cessation in women.
AB  - Gender data for bupropion suggest that it may be a particularly effective smoking
      cessation medication for women. It is not known whether the efficacy of this
      pharmacotherapy differs as a function of the psychotherapy with which it is
      administered. This study used a two level factorial design to examine the
      independent and interactive effects of medication (bupropion 300 mg/day vs.
      placebo) and psychotherapy (cognitive-behavioral therapy [CBT] vs. supportive
      therapy [ST]). In addition to testing the hypothesis that bupropion with CBT
      would be most effective of all the treatments, we examined medication compliance
      and its role in the efficacy of bupropion. Participants were 154 women, aged at
      least 30 years and smoking more than 10 cigarettes/day. Compliance with study
      medication was assessed using Medication Event Monitoring Systems (MEMS) over 7
      weeks of treatment. Psychological interventions were delivered in 60-min weekly
      group sessions. Longitudinal analysis of abstinence outcomes from end of
      treatment (EOT) through 12 months after treatment revealed a significant
      interaction of medication and therapy. Higher abstinence rates at EOT and 3-, 6-,
      9-, and 12-month follow-ups were observed when bupropion was delivered
      concurrently with CBT (44%, 24%, 30%, 23%, 17%) rather than with ST (18%, 1%, 8%,
      5%, 2%). The bupropion-CBT combination, however, was not clearly superior to
      placebo, regardless of therapy assignment. Higher rates of medication compliance
      were positively predictive of abstinence, and this effect was most evident in the
      placebo condition. Findings provide only modest support for CBT as the preferred
      type of intensive therapy in conjunction with bupropion in women.

PMID- 17558828
TI  - Achieving high rates of consent for genetic testing among African American
      smokers.
AB  - Genetic factors play an important role in smoking behavior. Although African
      Americans are at disproportionately increased risk for tobacco-related morbidity
      and mortality, limited attention has been given to genetic investigation of
      tobacco use in this population. The present study examined consent for genetic
      testing among African American smokers enrolled in a smoking cessation clinical
      trial. African American light smokers (</=10 cigarettes/day) enrolled in a
      smoking cessation study met with study counselors to review consent forms for an
      adjunct study and responded to a request for genetic analysis related to smoking.
      Participants completed assessment of demographic, psychosocial, and tobacco
      related variables. Of 755 clinical trial participants, 745 (99%) responded to the
      genetic consent form. Of participants who responded, 620 (83%) provided consent
      for blood collection for genetic analysis. No significant differences were
      identified between individuals who consented to genetic analysis and those who
      denied consent. This study demonstrated the feasibility of obtaining consent for
      genetic analysis for smoking-related investigation among African American
      smokers. Findings support the inclusion of African Americans within genetic
      investigation of tobacco use and treatment.

PMID- 17558829
TI  - Biologics and Behcet's: disease diversity and trial design.

PMID- 17558831
TI  - Course of macular edema in uveitis under medical treatment.
AB  - OBJECTIVE: To describe the response of uveitic macular edema to various treatment
      methods using optical coherence tomography (OCT). METHODS: This is a prospective
      study of consecutive uveitis patients with macular edema in at least one eye. The
      patients received medical treatment. Best corrected Snellen Visual Acuity (BCVA)
      and tomographic features of the macula, including macular thickness measurement,
      were obtained at one, three, six, and 12 months after commencing treatment.
      RESULTS: Eighty-one eyes of 58 patients were analyzed. Complete resolution of
      macular edema occurred in 38 eyes (47%). The average BCVA was 20/34 logarithm of
      minimum angle of resolution (-logMAR, 0.2 +/- 0.3) upon study entry and 20/27 (
      logMAR, 0.13 +/- 0.29) upon study completion. The difference was statistically
      significant (p = 0.04). The corresponding mean retinal thickness at the central
      fovea was 319 +/- 150 microm at the beginning of the study compared to 241 +/-
      125 microm at 12 months (p < 0.001). A weak but statistically significant
      correlation between the reduction of macular thickness and the improvement of
      BCVA (r = 0.3, p = 0.01) was found. Thirteen of the 43 eyes (30%) with persistent
      macular edema had a more than 15% reduction of macular thickness compared to
      baseline, whereas 10 eyes (23, 3%) had a more than 15% increase in macular
      thickness. Statistical analysis indicated that the presence of an epiretinal
      membrane and an OCT pattern of diffuse macular edema was a significant factor
      associated with medical treatment failure. CONCLUSION: This study demonstrates
      the overall favorable visual prognosis of uveitic macular edema under medical
      treatment. The presence of an epiretinal membrane is an important factor
      associated with medical treatment failure.

PMID- 17558830
TI  - A double-masked, randomized study to investigate the safety and efficacy of
      daclizumab to treat the ocular complications related to Behcet's disease.
AB  - PURPOSE: To investigate the safety and efficacy of daclizumab (Zenapax, humanized
      anti-Tac, HAT) in controlling the ocular manifestations of Behcet's disease.
      DESIGN: Randomized, placebo-controlled, double-masked clinical trial.
      PARTICIPANTS: Seventeen participants with Behcet's disease experiencing at least
      two prior ocular attacks and requiring treatment with immunosuppressive agents
      for the ocular complications of Behcet's disease. METHODS: Participants received
      either intravenous placebo or daclizumab (1 mg/kg) infusions every two weeks for
      six weeks, then every four weeks while continuing their standard
      immunosuppressive regimens. If clinically indicated, tapering of the standard
      immunosuppressive medications was allowed after six months of study enrollment.
      Complete ocular and physical examinations and an adverse event assessment were
      performed at baseline and prior to each study infusion. MAIN OUTCOME MEASURES:
      Primary safety endpoints were the development of a life-threatening complication
      or a severe opportunistic infection. Primary efficacy outcomes were the number of
      ocular attacks and an assessment of systemic immunosuppressive medications
      required during the study, including the ability to taper concomitant
      immunosuppressive therapy. RESULTS: Nine participants randomized to daclizumab
      and eight to placebo were followed monthly. Follow-up ranged from one to 34
      months, with a median follow-up of 15 months. Two participants randomized to
      daclizumab discontinued study therapy prior to the end of the study for personal
      reasons. No participant experienced a safety endpoint, and visual acuity remained
      stable in all participants during the course of the study. Ten participants (six
      daclizumab, four placebo) experienced ocular attacks requiring therapy. The
      median ocular attack rate during the study was greater in the daclizumab arm than
      the placebo arm (median 1.27 vs. 0.17 attacks/year, respectively). Participants
      in the placebo arm also experienced a greater reduction in the immunosuppressive
      medication score compared to participants receiving daclizumab (median -4.0 vs. 
      1.0, respectively). CONCLUSIONS: The observed results in the placebo group
      demonstrate that careful follow-up and treatment with standard combination
      immunosuppressive therapy can be effective for the management of the ocular
      complications of Behcet's disease. In our small study, there was no suggestion
      that daclizumab was beneficial in comparison with placebo. However, the low
      observed attack rate limited our ability to make a definitive treatment group
      comparison.

PMID- 17558832
TI  - Antibodies against calsequestrin and type XIII collagen are good markers for
      chronic upper eyelid retraction.
AB  - PURPOSE: Chronic upper eyelid retraction is a common manifestation of thyroid
      associated ophthalmopathy (TAO) but can occur as a dominant feature of
      ophthalmopathy in patients with Graves' hyperthyroidism and in association with
      Hashimoto's thyroiditis in the absence of other eye signs except mild proptosis.
      METHODS: We measured antibodies against calsequestrin, flavoprotein (Fp), G2s,
      and collagen XIII in an enzyme-linked immunosorbent assay (ELISA) in 15 patients
      with chronic upper eyelid retraction. RESULTS: Calsequestrin antibodies were
      detected in 67% of patients with upper eyelid retraction, Fp antibodies in 47%,
      G2s antibodies in 20%, and collagen XIII antibodies were detected in 40% of these
      patients at the first visit. These prevalences were significantly greater than
      normal for calsequestrin and collagen XIII, but not for Fp and G2s antibodies. On
      follow-up, calsequestrin antibodies were detected in two more patients, for an
      overall prevalence of 80%. Levels of the four antibodies remained fairly constant
      over the study period and generally correlated with the presence and severity of
      upper eyelid signs. CONCLUSIONS: These findings support the notion that
      autoimmune attack against calsequestrin and collagen XIII in the levator
      palpebrae superioris (LPS) muscle may play a role in the pathogenesis of upper
      eyelid retraction and that lid retraction may be the dominant feature of
      ophthalmopathy in patients with Hashimoto's thyroiditis and non-autoimmune
      thyroid disease. Because calsequestrin is an intracellular protein, the
      corresponding autoantibodies probably do not initiate LPS muscle inflammation but
      may contribute to its damage. The mix of antibodies against calsequestrin and
      collagen XIII may shed light on the diverse presentations found in thyroid
      associated ophthalmopathy.

PMID- 17558833
TI  - HLA typing in Vogt-Koyanagi-Harada syndrome in North Indian patients.
AB  - PURPOSE: To report the HLA profile of VKH patients from India. METHOD: Forty-one
      patients and 50 controls were studied. Phenotyping using a lymphocytotoxicity
      assay was done for HLA-A and -B. DNA-based sequence-specific low resolution
      typing was done for HLA-DR and -DQ loci. RESULTS: HLA-A9 was over-represented in
      the patient population (p = 0.01), whereas HLA-A11 (p = 0.03) and HLA-DRB1*13 (p
      = 0.007) were found to be underrepresented. The frequency of HLA-DRB1*04 was
      14.6% and 10% in the patient population and controls, respectively. The HLA-DQ
      frequencies did not differ significantly between patients and controls.
      CONCLUSION: Unlike that reported in most populations, we did not find a
      significant association between HLA-DRB1*04 and our patient population.

PMID- 17558834
TI  - Systemic immunomodulatory therapy in severe dry eye secondary to inflammation.
AB  - PURPOSE: To report four patients with unusually severe acute keratitis sicca
      secondary to lacrimal tissue and ocular surface inflammation who eventually
      required systemic immunosuppressive therapy. METHODS: Observational case series
      of four patients with extremely severe acute dry eye syndrome who were profoundly
      disabled by pain and photophobia (to the extent of staying in dark rooms) despite
      aggressive conventional therapy. Clinical data including visual acuities, other
      treatments administered for dry eye, systemic medical conditions, Schirmer and
      rose bengal staining results, degree of conjunctival injection, and medications
      were recorded. All four patients were treated with systemic immunomodulatory
      therapy. RESULTS: All four patients were female with a mean age at presentation
      of 40 years (range 22-58 years), and all had systemic autoimmune diseases:
      systemic lupus erythematosus (SLE) and Sjogren's syndrome (n = 2), Sjogren's
      syndrome (n = 1), rheumatoid arthritis (RA) and psoriasis (n = 1). Schirmer test
      values at onset ranged from 0 to 2 mm. All patients had failed aggressive
      lubrication, topical cyclosporine, lid care, and punctual plugs. In two patients,
      serum tears and hyphrecation punctal occlusion were tried without success.
      Various systemic immunosuppressive agents were used to control inflammation of
      the lacrimal glands: methotrexate and cyclosporine A (patient 1), cyclosporine A
      (patient 2), prednisone (patient 3), and methotrexate and infliximab (patient 4).
      Treatment with systemic immunomodulatory agents resulted in resolution of the
      acute inflammatory assault on the lacrimal glands and control of signs and
      symptoms of keratoconjunctivitis sicca in all four patients, and visual acuities
      improved in all of them. Post-treatment Schirmer values ranged from 7 to 10 mm.
      CONCLUSION: Systemic immunosuppressive agents may be required in the treatment of
      recalcitrant primary and secondary Sjogren's syndrome caused by systemic
      autoimmune conditions. We show that systemic immunomodulatory therapy leads to
      significantly improved tear production and resolution of the keratoconjunctivitis
      in these rare but severe cases.

PMID- 17558835
TI  - Apoptosis in orbital fibroadipose tissue and its association with clinical
      features in Graves' ophthalmopathy.
AB  - PURPOSE: To evaluate the rate of apoptosis in orbital fibroadipose tissue in
      Graves' ophthalmopathy (GO) patients and investigate its associations with
      disease characteristics. METHODS: Orbital tissue samples were obtained during
      decompression surgery from 25 GO patients. Disease activity was evaluated using
      the Clinical Activity Score, while the clinical features of GO were evaluated
      using the Total Eye Score (TES). Tissue samples of 12 patients without any
      thyroid or autoimmune disease were studied as controls. The rate of apoptosis was
      evaluated with a terminal deoxyribonucleotidyl transferase-mediated dUTP
      digoxigenin nick-end labeling (TUNEL) assay, and ultrastructural features of
      apoptosis were evaluated with electron microscopy. RESULTS: The rate of apoptosis
      in orbital fibroadipose tissue was significantly higher in GO cases than in the
      control group (p < 0.001) and significantly correlated with TES (r: 0.545; p =
      0.005). The rate of apoptosis was 7.9% +/- 6.5%, and 22.0% +/- 7.8% in type 1 and
      type 2 cases, respectively (p = 0.001). The rate of apoptosis was 21.6% +/- 7.5%
      in eyes showing dysthyroid optic neuropathy (DON) and 6.7% +/- 5.4% in eyes
      without DON (p = 0.005). CONCLUSIONS: The rate of apoptosis was high in the
      orbital fibroadipose tissue of GO cases and was related to the clinical features
      of the disease.

PMID- 17558836
TI  - Conjunctival involvement in Churg-Strauss syndrome.
AB  - PURPOSE: To describe an unusual case of Churg-Strauss syndrome (CSS) that
      presented with a conjunctival nodule and was successfully treated with oral
      corticosteroids. METHODS: Case report. RESULTS: A 30-year-old woman with a
      history of adult-onset asthma, seasonal allergies, and a lung mass presented with
      a nodular elevation of the conjunctiva. Excisional biopsy demonstrated
      necrotizing eosinophilic granulomas. Systemic evaluation revealed peripheral
      eosinophilia and elevated IgE, consistent with Churg-Strauss syndrome. The
      patient's symptoms and eosinophilia resolved after an increase in the dose of
      oral corticosteroids. CONCLUSIONS: This case describes a unique presentation of
      conjunctival involvement in CSS that differs from prior case reports by having a
      small, well-demarcated nodule and lacking signs of active inflammation.

PMID- 17558837
TI  - Mucormycosis endophthalmitis after cataract surgery.
AB  - PURPOSE: To describe a rare case of Mucor endophthalmitis that occurred in well
      controlled diabetes after cataract surgery. DESIGN: Interventional case report.
      METHODS: Description of case and review of literature. RESULTS/CONCLUSION: Mucor
      endophthalmitis may occur after cataract surgery and should be considered in the
      differential for patients with unresolving postoperative uveitis.

PMID- 17558838
TI  - Giant sarcoid tumor of the iris and ciliary body.
AB  - PURPOSE: To report the occurrence of a giant iridociliary sarcoid tumor. METHODS:
      The patient was evaluated by medical history, ophthalmoscopic examination
      (including photography and ultrasonography) as well as systemic, hematologic, and
      radiographic examinations. Tumor biopsies allowed for cytopathologic,
      histopathologic, and immunohistochemical analysis. RESULTS: The 39-year-old black
      male was found to have a right iris and ciliary body tumor. Ultrasonography
      revealed a 10 x 12-mm base, 5.6-mm height, low internal reflectivity, and
      vitreous debris. Radiographic imaging revealed mediastinal and bilateral hilar
      lymphadenopathy. A purified protein derivative (PPD) and a hematologic survey
      were negative. Pathology evaluations of the surgical specimens revealed features
      of non-caseating granulomata consistent with sarcoidosis. A combination of
      topical and systemic steroid therapy was locally curative. CONCLUSIONS: We
      describe a giant iridociliary sarcoid tumor in a patient with no lacrimal gland
      enlargement, conjunctival nodules, or skin lesions. A biopsy was required to
      establish the diagnosis.

PMID- 17558839
TI  - Serpiginous choroiditis-like picture due to ocular toxoplasmosis.
AB  - PURPOSE: To report an atypical presentation of ocular toxoplasmosis in the form
      of serpiginous choroiditis-like picture in an immunocompetent individual.
      METHODS:  CASE REPORT: A 32-year-old man with blurred vision in the left eye
      showed serpiginous choroiditis-like appearance. Fundus fluorescein angiography
      and relevant laboratory tests including anti-toxoplasma serology and polymerase
      chain reaction (PCR) in aqueous humor were performed. RESULTS: The serology in
      blood and PCR in aqueous humor were positive for Toxoplasma gondii infection. The
      patient was treated with anti-toxoplasma antimicrobials and systemic steroids. At
      the end of six weeks of treatment the fundus lesions had healed well, with good
      visual recovery. CONCLUSIONS: Serpiginous choroiditis-like picture can be an
      atypical manifestation of ocular Toxoplasma gondii infection.

PMID- 17558840
TI  - Linear corneal epithelial keratitis with a horseshoe pattern.
AB  - PURPOSE: To report the treatment and follow-up of a linear epithelial keratitis
      with a horseshoe pattern. METHODS: A 21-year-old Turkish soldier, who presented
      with epithelial keratitis with a horseshoe pattern that did not respond to
      immunosuppressive and multiple anti-microbial treatment, was studied clinically.
      RESULTS: No microorganism was identified with different stains, cultures, and
      herpes simplex virus-polymerase chain reaction. The impression cytology revealed
      prominent polymorphonuclear leukocyte infiltration at the keratitis line. The
      keratitis did not respond to different antimicrobial treatment or local and
      systemic corticosteroids. After a fourth scraping was perfomed deeply with a disc
      knife, the lesion healed and did not recur in six months. CONCLUSION: Linear
      epitheliitis of cornea with a horseshoe pattern was not found to be associated
      with any microorganism or systemic disease.

PMID- 17558841
TI  - Endogenous endophthalmitis due to Salmonella choleraesuis in an HIV-positive
      patient.
AB  - PURPOSE: To report a case of endogenous endophthalmitis caused by the gram
      negative bacterium Salmonella choleraesuis as a first sign of HIV infection in a
      patient from Thailand. METHOD: Case description and literature review. RESULTS: A
      54-year-old male without systemic complaints developed non-painful panuveitis in
      his left eye accompanied by high intraocular pressure. On investigation, HIV
      serology was found positive, and aqueous and blood cultures revealed the
      bacterium Salmonella choleraesuis. Despite aggressive treatment with antibiotics,
      the affected eye did not improve, and his visual acuity decreased to no light
      perception. CONCLUSIONS: Endogenous endophthalmitis with the non-typhoidal
      Salmonellae can occur in the absence of systemic symptoms in an immunocompromised
      host.

PMID- 17558842
TI  - Parinaud's oculoglandular syndrome due to herpes simplex virus type 1.
AB  - PURPOSE: To describe the clinical findings in a patient with Parinaud's
      oculoglandular syndrome as an uncommon manifestation of primary herpes simplex
      virus type 1 (HSV-1) infection. METHODS: The clinical course, the laboratory
      findings, the therapy, and the outcome regarding a 14-year-old girl are
      described. RESULTS: The culture and PCR detection of HSV-1 on conjunctiva and
      skin scrapings, along with seroconversion to HSV, confirmed the etiology. The
      oral and local acyclovir therapy led to a prompt improvement in the patient's
      symptoms. CONCLUSION: The solitary ocular-glandular syndrome due to HSV-1 primary
      infection has never been reported before. Parinaud's oculoglandular syndrome is
      found in 5% of patients with cat-scratch disease and only on rare occasion
      associated with other conditions. Herpetic infection should be considered in the
      differential diagnosis of young patients with conjunctivitis, periorbital
      swelling, and painful preauricular and submandibular lymphadenopathy, combined
      with systemic symptoms of malaise and fever.

PMID- 17558844
TI  - Methylenetetrahydrofolate reductase genetic polymorphisms in patients with
      primary open-angle glaucoma.
AB  - PURPOSE: Hyperhomocysteinemia has been found in patients with primary open-angle
      glaucoma. The purpose of the present study was to determine if
      hyperhomocysteinemia-associated polymorphisms of the methylenetetrahydrofolate
      reductase gene (MTHFR) are overrepresented in primary open-angle glaucoma.
      METHODS: Patients with primary open-angle glaucoma (n = 243) and controls (n =
      187) were analyzed for the MTHFR 677 C > T and 1298 A > C polymorphisms using
      minisequencing technique. RESULTS: No significant differences were observed in
      allele and genotype frequencies of the MTHFR 677C > T and 1298A > C polymorphisms
      between controls and the primary open-angle glaucoma group. CONCLUSIONS: If
      hyperhomocysteinemia is important in the pathogenesis of glaucoma, this study
      does not support a role for MTHFR polymorphisms in this context.

PMID- 17558845
TI  - Did Edgar Degas have an inherited retinal degeneration?
AB  - OBJECTIVE: Retrospective analysis of the famous painter Edgar Degas' eye disease.
      DESIGN: A historical review and analysis based on Degas' paintings and letters
      exchanged between the painter and his friends and family members, as well as on
      the chronicles of his associates. DeGas-Musson family papers at the Howard-Tilton
      Library of Tulane University are also reviewed. RESULTS: Degas had an eye disease
      that was first noticed in 1870 and that progressed throughout his life. He
      suffered from progressive bilateral central visual loss and light sensitivity
      which was most acutely recognized while he was visiting his mother's side of the
      family in New Orleans where he could not paint outside because of the bright sun.
      Edgar's maternal first cousin, Estelle Musson, also suffered gradual bilateral
      visual loss, and was also known to have light sensitivity early in her life.
      Estelle became totally blind in her early 30s. Both Edgar and Estelle were
      otherwise healthy and lived long lives. CONCLUSION: It is likely that Edgar Degas
      and his cousin Estelle Musson had a hereditary retinal degeneration primarily
      affecting their central vision. Degas' retinal disease undoubtedly affected his
      life and his art but did not prevent him from being one of the most admired
      painters of all times.

PMID- 17558846
TI  - Autosomal dominant cornea plana is not associated with pathogenic mutations in
      DCN, DSPG3, FOXC1, KERA, LUM, or PITX2.
AB  - PURPOSE: To determine the genetic basis of autosomal dominant cornea plana (CNA1)
      through the performance of a genome-wide linkage analysis and screening of the
      decorin (DCN), dermatan sulfate proteoglycan 3 (DSPG3), forkhead box C1 (FOXC1),
      keratocan (KERA), lumican (LUM,) and paired-like homeodomain transcription factor
      2 (PITX2) genes in members of an affected multigenerational family. METHODS:
      Cycloplegic refraction, slit lamp biomicroscopy, corneal pachymetry, and corneal
      topography were performed to determine each patient's affected status. DNA was
      obtained from affected and unaffected subjects for the performance of a genome
      wide linkage analysis as well as PCR amplification and sequencing of DCN, DSPG3,
      FOXC1, KERA, LUM, and PITX2. RESULTS: Five affected and three unaffected
      individuals were examined and provided a peripheral blood sample for DNA
      isolation. All affected individuals demonstrated an average corneal dioptric
      power less than 39 D, as well as one or more of the following anomalies: high
      hyperopia, strabismus, microcornea, posterior embryotoxon, iridocorneal
      adhesions, iris atrophy, and pupillary irregularities. A genome-wide linkage
      analysis did not indicate or exclude linkage to the region on chromosome 12 to
      which CNA1 has been previously mapped, and did not provide a single or multipoint
      LOD score greater than 2.0 for any of the 400 microsatellite markers. Screening
      of DCN, DSPG3, FOXC1, KERA, LUM, and PITX2 revealed 12 previously described
      single nucleotide polymorphisms, 2 previously described duplications, and 1
      previously described insertion. None of the mutations previously associated with
      autosomal recessive cornea plana (CNA2) were identified. Seven novel sequence
      variants were described, including 5 single nucleotide substitutions, 1 insertion
      and 1 deletion. None of the identified sequence variants demonstrated complete
      segregation with the affected phenotype in the pedigree. CONCLUSION: Although
      missense and nonsense mutations in KERA are associated with CNA2, we did not
      identify any of the previously described mutations or novel mutations that
      segregated with the disease phenotype in a family with CNA1. In addition, no
      pathogenic sequence variations were found in DCN, DSPG3, LUM, PITX2 and FOXC1,
      which have also been implicated in corneal and anterior segment dysgenesis.

PMID- 17558847
TI  - Chromosomal abnormalities and glaucoma: a case of congenital glaucoma associated
      with 9p deletion syndrome.
AB  - PURPOSE: To present a case of congenital glaucoma associated with 9p22.3-pter
      deletion as the sole identified genetic abnormality. To compile cases of
      chromosome 9p deletion associated with congenital glaucoma from the literature.
      METHOD: A review of case notes of the proband. Literature search using PubMed and
      Medline to identify other cases of chromosome 9p deletion associated with
      congenital glaucoma. RESULTS: A total of four cases of chromosome 9p deletion
      associated with congenital glaucoma have now been reported in the literature.
      CONCLUSION: A female infant with a chromosome 9p22.3-pter deletion presented with
      congenital glaucoma in addition to systemic features typical of the 9p deletion
      syndrome. Congenital glaucoma is not an invariant feature of 9p deletion
      syndrome, nonetheless, 9p24 may localise a gene implicated in the condition.

PMID- 17558848
TI  - A rare transthyretin mutation (Asp18Glu) associated with vitreous amyloid.
AB  - Amyloidosis is a term to describe extracellular deposition of insoluble beta
      fibrillar proteins. Here we describe a patient who was confirmed to have
      amyloidosis after right heart biopsy and was found to have DNA change 114T > A
      (codon change D18E). Ophthalmic examination showed increasing vitreous sheet-like
      opacities in the left eye and she subsequently underwent vitrectomy. The
      vitrectomy specimen was confirmed to have amyloid involvement. To our knowledge
      this is the first report of vitreous involvement of a patient with the Asp18Glu
      mutation of the transthyretin (TTR) gene with DNA change 114T > A.

PMID- 17558849
TI  - Intron 4 VNTR of endothelial nitric oxide synthase (eNOS) gene and diabetic
      retinopathy in type 2 patients in southern India.
AB  - A 27-bp variable number tandem repeat (VNTR) in intron 4 of endothelial nitric
      oxide synthase (eNOS) gene has been associated with the risk for developing
      diabetic retinopathy (DR) in various ethnic populations. Hundred and eighty seven
      patients with retinopathy (cases; DR+) and 188 patients without retinopathy
      (controls: DR-) from southern India who had type 2 diabetes mellitus (T2DM) for
      more than 10 years, were included in the study. We could neither find significant
      allelic association with clinical severity of DR nor with macular edema. Our
      results suggest lack of association of intron 4 VNTR of eNOS gene with DR in
      southern India.

PMID- 17558850
TI  - Unilateral ocular duplication.
AB  - PURPOSE: To present a boy with unilateral duplication of the eye. METHOD: The
      case history is described from the first visit at birth to the age of 14 years.
      RESULTS: A review of the literature shows that this malformation is compatible
      with life although malformations of the brain and epilepsy have been reported in
      all cases where a paediatric exam was described. We show that the malformation
      can appear as a synophthalmic eye in a single orbit or as two separate unilateral
      eyes in a separate orbit. CONCLUSION: We find the denomination, triophthalmia
      insufficient to differentiate between the two types and suggest a differentiation
      between unilateral synophthalmia and ipsilateral ocular duplication.

PMID- 17558851
TI  - Gillespie syndrome: additional findings and parental consanguinity.
AB  - Aniridia is a rare condition whose presence should alert clinicians to the
      possibility of other abnormalities. One of the differential diagnoses that should
      be considered is Gillespie syndrome, in which aniridia is associated with
      cerebellar ataxia and mental retardation. There are only 21 reported cases of
      Gillespie syndrome. The goal of this paper is to describe the clinical
      manifestations of a girl born to a consanguineous couple who presented with
      typical findings of the Gillespie syndrome, in addition to previously undescribed
      alterations of her distal extremities.

PMID- 17558852
TI  - Bardet-Biedl Syndrome in an African-American patient: should the diagnostic
      criteria be expanded to include hydrometrocolpos?
AB  - Bardet-Biedl Syndrome (BBS) is a multisystemic disorder diagnosed on the basis of
      a combination of primary and secondary clinical features that include retinal
      dystrophy, obesity, polydactyly, cognitive dysfunction, and renal malformations.
      We report a unique case of BBS in a 13-year old girl of African-American descent
      who presented with retinitis pigmentosa, obesity, polydactyly, learning
      disabilities, precocious puberty, hypertension, renal cysts, and Hirschprung
      disease. Further evaluation revealed a history of precocious puberty, which is
      antithetical to the common manifestations of BBS, while neuroimaging was
      suggestive of periventricular leukomalacia and neuro-electrophysiologic studies
      revealed diffuse cerebral disturbance, which may contribute to her neurological
      abnormalities. The patient was also diagnosed with hydrometrocolpos, a finding
      typical of McKusick-Kaufman Syndrome (MKKS) but infrequent in other disorders.
      This observation, together with recent findings in some mouse models of BBS,
      raises the question of whether hydrometrocolpos should be considered as an
      additional diagnostic criterion for BBS to be used in females in parallel to the
      criterion of hypogonadism in males, thereby improving diagnostic sensitivity.

PMID- 17558853
TI  - Vision impairment with an interstitial deletion of the short arm of chromosome 8.
AB  - We describe the phenotype of a male infant with an interstitial deletion of the
      short arm of chromosome 8 (p. 11.2-p. 21). Visual impairment is a major feature
      in this case. The clinical, radiographic and electrodiagnostic findings are
      presented. Only four other cases have been reported in which visual problems are
      associated with a deletion of 8 p.

PMID- 17558854
TI  - Ocular anomalies associated with interstitial deletion of chromosome 2q31: case
      report and review.
AB  - We describe a newborn girl with multiple malformations associated with an
      interstitial deletion of chromosome 2q (q24q32). Clinical findings included
      growth retardation, microcephaly, facial malformations, common atrioventricular
      canal, digital anomalies of both hands and feet, and ovarian hypoplasia.
      Bilateral ocular anomalies included down-slanting palpebral fissures,
      blepharophimosis, microphthalmia, uveal coloboma, and corneal opacity.
      Chromosomal segment 2q31 may play a major role in the development of the eye and
      its adnexa.

PMID- 17558855
TI  - Recommendations for lipid testing and reporting by Australian pathology
      laboratories.

PMID- 17558856
TI  - Glutathione S-transferase pi (GSTP1) hypermethylation in prostate cancer: review
      2007.
AB  - Prostatic carcinoma is characterised by the silencing of the pi-class glutathione
      S-transferase gene (GSTP1), which encodes a detoxifying enzyme. The silencing of
      GSTP1 results from aberrant methylation at the CpG island in the promoter-5' and
      occurs in the vast majority of cases of high-grade prostatic intraepithelial
      neoplasia (PIN) and prostate cancers. We review the potential novel role of GSTP1
      and its related expression in prostate cancer. The loss of expression (silencing)
      of the GSTP1 gene is the most common (>90%) genetic alteration reported to date
      in prostate cancer. Quantitative methylation-specific PCR assays allow detection
      of GSTP1 methylation in prostate biopsies and may improve the sensitivity of
      cancer detection. Advances in the epigenetic characterisation of prostate cancer
      have enabled the development of DNA methylation assays that may soon be used in
      diagnostic testing of serum and tissue for prostate cancer. Inhibition of
      aberrant promoter methylation could theoretically prevent carcinogenesis.

PMID- 17558857
TI  - The role of epithelial-mesenchymal transition in cancer pathology.
AB  - Invasion, the hallmark of malignancy, consists in the translocation of tumour
      cells from the initial neoplastic focus into neighbouring host tissues, and also
      allows tumour cells to penetrate vessel endothelium and enter the circulation to
      form distant metastasis. A histological pattern found at the periphery of
      carcinomas is the presence of individual malignant cells detached from the tumour
      mass and staying independently within the interstitial matrix of the stroma.
      While they are readily identified by the pathologist as invading malignant cells,
      their relationship with the compact-appearing portions of the tumour as well as
      the mechanism underlying the development of this pattern are not immediately
      evident at histological level. There is growing evidence suggesting that this
      change in tumour tissue architecture takes place through a peculiar phenotype
      modulation known as epithelial-mesenchymal transition (EMT). The essential
      features of EMT are the disruption of intercellular contacts and the enhancement
      of cell motility, thereby leading to the release of cells from the parent
      epithelial tissue. The resulting mesenchymal-like phenotype is suitable for
      migration and, thus, for tumour invasion and dissemination, allowing metastatic
      progression to proceed. Although the molecular bases of EMT have not been
      completely elucidated, several interconnected transduction pathways and a number
      of signalling molecules potentially involved have been identified. These include
      growth factors, receptor tyrosine kinases, Ras and other small GTPases, Src, beta
      catenin and integrins. Most of these pathways converge on the down-regulation of
      the epithelial molecule E-cadherin, an event critical in tumour invasion and a
      'master' programmer of EMT. E-cadherin gene is somatically inactivated in many
      diffuse-type cancers such as lobular carcinoma of the breast and diffuse gastric
      carcinoma, in which neoplastic cells through the entire tumour mass have lost
      many of their epithelial characteristics and exhibit a highly invasive, EMT
      derived histological pattern. E-cadherin down-modulation is also seen in solid,
      non-diffuse-type cancers at the tumour-stroma boundary where singly invading, EMT
      derived tumour cells are seen in histological sections. In this latter scenario,
      E-cadherin loss and EMT could be transient, reversible processes possibly
      regulated by the tumour microenvironment and, as a matter of fact, neoplastic
      cells that have undergone EMT during invasion seem to regain E-cadherin
      expression and their epithelial, cohesive characteristics at the secondary foci.
      Since the molecules involved in EMT represent potential targets for
      pharmacological agents, these findings open new avenues for the control of
      metastatic spread in the treatment of malignancies.

PMID- 17558858
TI  - Analysis of APC/beta-catenin genes mutations and Wnt signalling pathway in
      desmoid-type fibromatosis.
AB  - OBJECTIVE: The abnormalities of the Wnt signalling pathway in desmoid-type
      fibromatosis were analysed, with the purpose of exploring the mechanism of
      tumorigenesis and progression. METHODS: The clinical and histopathological
      features of 96 cases were analysed. Beta-catenin, cyclin-D1, c-myc, and Ki-67
      proteins were detected in 69 cases using formalin-fixed, paraffin-embedded
      tissues. Using the same materials, apoptosis of the tumour cells was investigated
      by terminal deoxynucleotidyl transferase mediated dUTP nick end-labelling (TUNEL)
      testing. Polymerase chain reaction (PCR), denaturing high performance liquid
      chromatography (DHPLC) assay, and sequencing were performed to detect
      abnormalities of the adenomatous polyposis coli (APC) and beta-catenin genes.
      RESULTS: APC gene mutations were found in 18 cases (26.1%, 18/69). Somatic
      mutations of codon 41 in exon 3 of beta-catenin were detected in 13 cases (18.8%,
      13/69). No correlation of beta-catenin abnormal expression with the mutations of
      APC gene or beta-catenin gene was identified (p>0.05). The cases with abnormal
      beta-catenin expression showed a higher level of c-myc protein expression (69.7%,
      23/33) than those without (22.2%, 8/36, p = 0.001). The apoptotic indices (AIs)
      were significantly lower in cyclin-D1 positive cases and c-myc positive cases (p
      = 0.015, p = 0.007). CONCLUSIONS: There are somatic mutations of the APC and beta
      catenin gene in desmoid-type fibromatosis, and there are abnormalities in the Wnt
      signalling pathway. These abnormalities may result in aberrant cell proliferation
      and apoptosis, which are likely to be important factors in tumorigenesis and
      progression.

PMID- 17558859
TI  - Increased expression of Gab2, a scaffolding adaptor of the tyrosine kinase
      signalling, in gastric carcinomas.
AB  - AIMS: Mounting evidence indicates that alterations of protein kinase signalling
      pathways play crucial roles in the pathogenesis of cancers. Gab2 (Grb2-associated
      binding protein 2), a member of the family of Gab scaffolding adaptors, transmits
      and amplifies the signals from receptor tyrosine kinases. A recent study
      demonstrated that Gab protein was over-expressed in breast cancers, and the over
      expressed Gab2 increased proliferation and invasion of the cells, indicating that
      Gab2 is an oncogenic protein. However, the roles of Gab in other cancers are
      largely unknown. METHODS: In this study, to see whether Gab2 expression could be
      a characteristic of gastric cancers, we analysed the expression of Gab2 in 60
      gastric adenocarcinomas by immunohistochemistry using a tissue microarray.
      RESULTS: In the normal gastric mucosal epithelial cells, Gab2 protein was
      expressed in parietal and zymogen cells, but not in other mucosal epithelial
      cells. In the cancer cells, Gab2 expression was detected in 40 (67%) of the 60
      gastric adenocarcinomas. The Gab2 expression was observed in 12 (60%) of the 20
      early gastric carcinomas and 28 (70%) of the 40 advanced gastric carcinomas.
      There was no significant association of Gab2 expression with clinocopathological
      characteristics, including invasion, metastasis and stage. CONCLUSION: Our data
      indicate that Gab2 over-expression is a feature not only of breast cancers, but
      also of gastric cancers. Increased expression of Gab2 in malignant gastric cells
      compared with normal epithelial cells suggests that Gab2 expression may play a
      role in gastric cancer development.

PMID- 17558860
TI  - Mutational analysis of caspase-14 gene in common carcinomas.
AB  - AIMS: Whereas most caspases play roles in apoptosis and/or inflammation, caspase
      14 plays a main role in epithelial differentiation. In cancers, expression of
      caspase-14 is frequently altered and is associated with some clinicopathological
      characteristics, suggesting caspase-14 might contribute to the pathogenesis of
      cancers. As a potential mechanism of caspase-14 alterations in cancers, we
      explored the possibility that mutation of caspase-14 gene is a characteristic of
      human cancers. METHODS: We analysed the entire coding region and all splice sites
      of human caspase-14 gene for the detection of somatic mutations in a series of
      345 cancers, including 105 colorectal, 60 gastric, 60 hepatocellular, 60 breast
      and 60 lung carcinomas, by a single-strand conformation polymorphism (SSCP)
      assay. RESULTS: Overall, we detected two somatic mutations of caspase-14 gene,
      which consisted of one missense mutation (S32Y) and one silent mutation (T234T).
      The caspase-14 mutations were detected in two of 105 colorectal carcinomas
      (1.9%), but not in other carcinomas. CONCLUSION: These data indicate that caspase
      14 gene is rarely mutated in colorectal carcinomas, but not mutated in gastric,
      lung, breast and hepatocellular carcinomas. The data also suggest that the
      caspase-14 mutation may not be a direct target of inactivation in tumorigenesis
      of common carcinomas.

PMID- 17558861
TI  - Cumulative expression of HIF-1-alpha, Bax, Bcl-xL and P53 in human colorectal
      cancer.
AB  - AIMS AND METHODS: Hypoxia-inducible factor (HIF-1) which contains oxygen
      regulated HIF-1alpha subunit maintains cytoprotective defence against hypoxic
      injury by induction of numerous genes. However, apoptotic regulators such as Bcl
      xL, Bax and P53 have not been associated with HIF-1 dependent regulation in
      immunohistochemical evaluation of human colorectal cancer tumours so far. Thus,
      we visualised these proteins immunohistochemically and using Spearman's test
      compared for the first time their expression in regard to different
      clinicopathological traits in 123 (113 for P53 evaluation) human colorectal
      cancers. RESULTS: HIF-1alpha correlated with Bcl-xL or Bax in all patients and
      particularly in node negative and node positive cancers, deeper intramural
      tumours (pT3+pT4) and adenocarcinomas. There was no significance in a small group
      of tumours with lesser extent through intestinal walls (pT1+pT2). In addition HIF
      1alpha associated with Bcl-xL in mucinous cancers. Moreover, HIF-1alpha
      correlated with Bcl-xL or Bax in moderately (G2) and poorly differentiated (G3)
      cancers, rectal and colonic tumours and in different sex and age groups. P53
      correlated only with Bax exclusively in younger patients. CONCLUSIONS: HIF-1alpha
      may influence expression of Bax or Bcl-xL, at least indirectly, as correlations
      between HIF-1alpha and Bax or Bcl-xL occur constantly.

PMID- 17558862
TI  - Pathophysiological mechanism of lung injury in patients with leptospirosis.
AB  - AIMS: Acute lung injury (ALI) is a serious clinical problem. We investigated the
      pathogenetic mechanisms of ALI caused by leptospirosis. METHODS: The study
      included five cases of leptospirosis. We monitored the arterial pressure (AP) and
      heart rate (HR) and analysed the AP and HR variabilities for assessment of
      autonomic functions. Histopathological changes in the lung, brain, kidney, and
      liver were examined. In addition, we identified the expression of inducible
      nitric oxide synthase (iNOS) using immunohistochemical stain. RESULTS: Five
      patients associated with leptospirosis died of ALI. Before death, severe
      hypotension and bradycardia occurred. Spectral analysis of AP and HR
      variabilities indicated decreased sympathetic drive with increased
      parasympathetic activity. Pathological examinations revealed alveolar haemorrhage
      and necrotic lesions in various organs. Immunohistochemical stain disclosed iNOS
      activity in multiple organs. Biochemical determinations indicated hypoxia,
      hyperglycaemia, increased nitrite/nitrate, methyl guanidine and other factors.
      CONCLUSIONS: These changes suggest that leptospirosis causes severe hypotension
      and bradycardia accompanied by autonomic dysfunction. Finally, multiple organ
      failure and damage ensued. The pathogenesis of lung and organ injury may involve
      iNOS and NO production.

PMID- 17558863
TI  - Efficient DNA extraction from 25-year-old paraffin-embedded tissues: study of 365
      samples.
AB  - AIMS: Archival fixed paraffin-embedded tissue (PET) is a valuable source for
      population-based molecular genetic studies but the extraction of high quality DNA
      is still a problematic issue. The present study tested the grade of DNA
      fragmentation and the DNA adequacy for genetic investigations in a large series
      of tissue specimens that were formalin- or Bouin-fixed and paraffin-embedded
      between 1979 and 1983. Specific aims were to: (1) estimate the amount of archival
      tissue samples from which DNA is recoverable by conventional methods and the
      influence of variables (origin, fixative, section size) on DNA recovery; and (2)
      evaluate the feasibility of genetic investigations in large scale population
      studies. METHODS: DNA was extracted in 2005 from 365 PET samples from Italy and
      Spain and subjected to PCR analysis targeting fragments of 152, 268 and 676 bp of
      the beta-globin gene. RESULTS: Amplification of a 152 bp fragment was obtained in
      252/365 (69%) PET samples, a 268 bp fragment in 62/365 (17%), a 676 bp fragment
      in 19/365 (5%) and no amplification for any fragment was obtained in 113/365
      (31%). A second processing of newly cut sections performed in a 25% simple random
      sample gave comparable results, with substantial concordance between the first
      and second tests (kappa value 0.62 [95% CI 0.59-0.64]). CONCLUSIONS: The results
      of this study show that DNA can be efficiently extracted from PETs archived for
      more than 20 years, and that large scale population studies based on PCR
      amplification of short target sequences are feasible.

PMID- 17558864
TI  - Clinical utility of serum soluble transferrin receptor levels and comparison with
      bone marrow iron stores as an index for iron-deficient erythropoiesis in a
      heterogeneous group of patients.
AB  - AIM: To evaluate the correlation between raised soluble transferrin receptor
      (sTfR) and stainable marrow iron, and to define the utility of sTfR in
      discriminating between the presence or absence of iron-deficient erythropoiesis
      in patients with anaemia of chronic disease. METHODS: Seventy-six consecutive
      adult patients without accelerated erythropoiesis who had undergone bone marrow
      (BM) aspiration/trephine for various clinical reasons during 2003-2006 were
      studied. All patients had serum iron studies (iron, transferrin and ferritin) and
      sTfR performed within 1 week of BM aspiration/trephine. These 76 patients were
      assigned to three groups based on the iron status of the BM and sTfR level:
      patients with normal sTfR and normal BM iron stores (n = 49), patients with an
      elevated sTfR and normal BM iron stores (n = 13) and patients reduced or absent
      BM iron stores (n = 14). Means (95% confidence interval) for mean corpuscular
      volume (MCV), mean corpuscular haemoglobin concentration (MCHC), red blood cell
      haemoglobin (RBC Hb) content and median (5th and 95th percentiles) for
      haemoglobin were then calculated. RESULTS: All patients with absent BM iron
      stores had an elevated sTfR level. Patients with normal BM iron stores and
      elevated sTfR levels had significantly lower Hb, MCV, MCHC and RBC Hb content
      than patients with normal BM iron stores and normal sTfR levels. CONCLUSION: sTfR
      is the most sensitive serum biochemical marker for the identification of iron
      deficient erythropoiesis. Normal BM iron stores can coexist with elevated sTfR
      and decreased MCV and MCHC. sTfR levels correlate better than BM iron stores with
      decreased MCV and MCHC. Therefore, sTfR is a useful marker of iron-deficient
      erythropoiesis, due to both absent iron stores, and restricted iron supply due to
      anaemia of chronic disease. As a single investigation, however, sTfR does not
      discriminate between these two causes of iron-deficient erythropoiesis.

PMID- 17558865
TI  - Test and teach. An unusual supraclavicular lump. Ossifying fibromyxoid tumor.

PMID- 17558866
TI  - Epstein-Barr virus associated leiomyosarcoma in a patient with systemic lupus
      erythematosus.

PMID- 17558867
TI  - Collagenous spherulosis with lobular carcinoma in situ: a potential diagnostic
      pitfall.

PMID- 17558868
TI  - Signet ring sinus histiocytosis incidentally detected in an autopsy case of
      diabetic nephropathy.

PMID- 17558869
TI  - Diagnosis of primary ureteral small cell carcinoma in instrumented urine
      cytology.

PMID- 17558870
TI  - Paratesticular rhabdomyoma.

PMID- 17558871
TI  - Ocular involvement by T-cell post-transplant lymphoproliferative disorder of
      cutaneous origin.

PMID- 17558872
TI  - Inflammatory malignant fibrous histiocytoma originating from the infratemporal
      fossa and extruding into the external auditory meatus.

PMID- 17558873
TI  - Mirror syndrome: a rare entity.

PMID- 17558874
TI  - Detection of vancomycin heteroresistant Staphylococcus haemolyticus and
      vancomycin intermediate resistant Staphylococcus epidermidis by means of
      vancomycin screening agar.

PMID- 17558877
TI  - Outcomes research in the ICU: an aid in defining the role of physiotherapy.
AB  - The economic reality of consumers, funders, and regulatory agencies demanding
      evidence regarding the quality of care patients are receiving in the intensive
      care unit (ICU) will have an effect on many of the routinely used practices in
      ICU, including physiotherapy. Outcomes research is a method that has been used to
      obtain evidence for the medical and respiratory management of patients in ICU. An
      overview of the literature was conducted to answer the following questions: 1.
      What is outcomes research? 2. Which outcomes should be measured in the adult
      critical care environment? 3. Which outcomes are physiotherapists currently
      including in research reports? Outcomes research is recognized by critical care
      specialists as a cost-effective method of determining what works in the real
      world. The value of physiologic measures is questioned, whereas the importance of
      patient centered, economic, and traditionally accepted outcome measures is
      increasingly being recognized. Most physiotherapy research reports still include
      physiologic measurements as the primary outcome of an intervention. Outcomes
      research provides researchers with the tools to define the role of the
      physiotherapist in the critical care environment. The outcomes measured must be
      relevant to patients, families, and funders.

PMID- 17558878
TI  - The current theoretical assumptions of the Bobath concept as determined by the
      members of BBTA.
AB  - The Bobath concept is a problem-solving approach to the assessment and treatment
      of individuals following a lesion of the central nervous system that offers
      therapists a framework for their clinical practice. The aim of this study was to
      facilitate a group of experts in determining the current theoretical assumptions
      underpinning the Bobath concept.A four-round Delphi study was used. The expert
      sample included all 15 members of the British Bobath Tutors Association. Initial
      statements were identified from the literature with respondents generating
      additional statements. Level of agreement was determined by using a five-point
      Likert scale. Level of consensus was set at 80%. Eighty-five statements were
      rated from the literature along with 115 generated by the group. Ninety-three
      statements were identified as representing the theoretical underpinning of the
      Bobath concept. The Bobath experts agreed that therapists need to be aware of the
      principles of motor learning such as active participation, opportunities for
      practice and meaningful goals. They emphasized that therapy is an interactive
      process between individual, therapist, and the environment and aims to promote
      efficiency of movement to the individual's maximum potential rather than normal
      movement. Treatment was identified by the experts as having "change of functional
      outcome" at its center.

PMID- 17558879
TI  - Clinical databases in physical therapy.
AB  - Clinical databases in physical therapy provide increasing opportunities for
      research into physical therapy theory and practice. At present, information on
      the characteristics of existing databases is lacking. The purpose of this study
      was to identify clinical databases in which physical therapists record data on
      their patients and treatments and to investigate the basic aspects, data sets,
      output, management, and data quality of the databases. Identification of the
      databases was performed by contacting members of the World Confederation for
      Physical Therapy, searching Pubmed, searching the Internet, and snowball
      sampling. A structured questionnaire was used to study the characteristics of the
      databases. The search was restricted to North America, Australia, Israel, and
      Western Europe. Seven clinical databases on physical therapy were identified.
      Four databases collected data on specific patient categories, whereas the others
      collected data on all patients. All databases collected data on patient
      characteristics, referrals, diagnoses, treatments, and closure, whereas some
      databases also collected functional status information. The purposes of the
      databases were diverse, but they can be summarized as quality improvement,
      research, and performance management. Although clinical databases are new to the
      field, they offer great potential for physical therapy research. Potential can be
      increased by further cooperation among databases allowing international
      comparative studies.

PMID- 17558880
TI  - Reliability of arthrometric measurement of shoulder lateral rotation movement in
      healthy subjects.
AB  - Numerous pathologic conditions of the shoulder result in loss of range of motion
      with lateral rotation being one of the most affected movements. Therefore, it is
      essential to know the reliability of the methods to measure this motion from a
      treatment evaluation perspective. The purpose of this study was to examine the
      reliability of the shoulder lateral rotation movement measured by an arthrometric
      method. Fifteen healthy subjects participated in the study. The passive range of
      motion in lateral rotation of the shoulder was measured with an arthrometric
      method for three positions of shoulder abduction and with three loads. Two
      evaluators took each measurement on two separate occasions. The reliability was
      good at 60 degrees and 90 degrees abduction with dependability indexes (phi)
      ranging from 0.77 to 0.87 and SEMs lower than 5 degrees. The reliability at 25
      degrees abduction was lower with dependability indexes (phi) ranging from 0.52 to
      0.66 and SEMs of 7 degrees or 8 degrees. Reliability was highest with the
      heaviest load reaching 0.66, 0.84, and 0.87 for the 25 degrees, 60 degrees, 90
      degrees abduction angles, respectively. In all conditions of measurement,
      differences between intratester and intertester reliability were minimal.
      Reliability of the shoulder lateral rotation measured by arthrometry was
      dependent on angle of abduction and load used to move the shoulder. Further
      studies are needed to confirm these findings in individuals with impaired
      shoulders.

PMID- 17558881
TI  - Active movement measurements of the shoulder girdle in healthy subjects with
      goniometer and tape measure techniques: a study on reliability and validity.
AB  - In response to the current need to develop objective measurement techniques for
      active movements of the shoulder girdle, this study had two goals: 1) to evaluate
      the reliability of the active range of motion (AROM) of shoulder girdle in
      elevation, protraction, and retraction with use of a goniometer and a tape
      measure and 2) to present the criterion-related validity of the reliable
      movements. Thirty healthy subjects performed two trials of each shoulder girdle
      AROM. They were assessed by two physical therapists, who used both evaluation
      techniques on two occasions. The generalizability theory was used to compute
      intratester (test-retest) and intertester reliability using dependability
      coefficients (phi) and standard errors of measurement (SEMs). The shoulder girdle
      movements were then evaluated with a movement analysis system (Optotrak 3020).
      The Pearson product-moment correlation coefficient (r) and paired t-tests were
      used to compare the results of clinical measurements with those of the movement
      analysis system. Overall, the reliability with the tape measure was good (phi =
      0.78-0.91; SEM's = 0.7-1.1 cm) for the elevation motion. The goniometer was only
      reliable for intratester measures (phi = 0.78-0.79; SEM = 2.7 degrees) for the
      elevation motion. Retraction was reliable with the tape measure alone (phi = 0.76
      0.84; SEM's = 0.5-0.7 cm). The criterion-related validity analysis revealed that
      measuring shoulder girdle elevation with the tape measure and goniometer, and
      retraction with the tape measure were not valid when evaluated against a gold
      standard, thus, both techniques have limitations in assessing true elevation and
      retraction measurements.

PMID- 17558882
TI  - Unintended effects of poverty programmes on childbearing in less developed
      countries: experimental evidence from Latin America.
AB  - Because conditional cash transfer (CCT) programmes (which make payments to poor
      households, conditional on their behaviour) potentially affect both household
      resource levels and parental preferences for quality vs. quantity of children,
      they may have unintended consequences for fertility. We use panel data from
      experimental CCT programmes in three Latin American countries to assess the
      unintended impact of these programmes on childbearing. Our findings, based on
      difference-in-difference models, show that the programme in Honduras, which
      inadvertently created large incentives for childbearing, may have raised
      fertility by between 2 and 4 percentage points. The CCT programmes in the two
      other countries, Mexico and Nicaragua, did not have the same unintended
      incentives for childbearing, and in these countries we found no net impact on
      fertility. Subsequent analysis examined several potential mechanisms by which
      fertility in Honduras may have been raised but was not able to identify a primary
      mechanism with the available data.

PMID- 17558883
TI  - The narrowing sex differential in life expectancy in high-income populations:
      effects of differences in the age pattern of mortality.
AB  - Using data from the Human Mortality Database for 29 high-income national
      populations (1751-2004), we review trends in the sex differential in e(0). The
      widening of this gap during most of the 1900s was due largely to a slower
      mortality decline for males than females, which previous studies attributed to
      behavioural factors (e.g., smoking). More recently, the gap began to narrow in
      most countries, and researchers tried to explain this reversal with the same
      factors. However, our decomposition analysis reveals that, for the majority of
      countries, the recent narrowing is due primarily to sex differences in the age
      pattern of mortality rather than declining sex ratios in mortality: the same rate
      of mortality decline produces smaller gains in e(0) for women than for men
      because women's deaths are less dispersed across age (i.e., survivorship is more
      rectangular).

PMID- 17558884
TI  - Son preference, use of maternal health care, and infant mortality in rural China,
      1989-2000.
AB  - This study assesses the effects of socio-economic conditions and the interaction
      between son preference and China's one-child family planning policy on the use of
      maternal health care services and their effects on infant mortality in rural
      China, using nationally representative data from the 2001 National Family
      Planning and Reproductive Health Survey. The results show that while the use of
      maternal health care services has continued to increase over time, large gaps
      still exist in the use of these services and in infant survival by mother's
      education, community income, and parity. Further improvements in the reproductive
      health of all women and in infant survival will require effective reduction of
      the obstacles to the use of maternal health care among those women in rural China
      who are less educated, poor, and of higher parity.

PMID- 17558885
TI  - Motherhood status and union formation in Moshi, Tanzania 2002-2003.
AB  - Age at first union is increasing throughout much of sub-Saharan Africa at the
      same time that not all couples are waiting for marriage before their first sexual
      intercourse. We assessed the effect of a premarital first birth on entrance into
      a first union in an urban area in East Africa -- Moshi, Tanzania. The data come
      from the Moshi Infertility Survey of 2002-2003. Women who spent less than a year
      in single motherhood were significantly more likely than childless women to enter
      into a first union, although the magnitude of this relationship was weaker for
      more recent cohorts. Women who had been single mothers for 5 or more years (about
      two-thirds of women with a premarital birth) were significantly less likely than
      women without children to enter into a first union.

PMID- 17558886
TI  - Living arrangements of migrant and Dutch young adults: the family influence
      disentangled.
AB  - The purpose of this study was to examine the impact of the family of origin on
      whether migrant and Dutch young adults live in the parental home. Using a sample
      of 1,678 young adults aged between 15 and 30 years from 847 families with five
      different ethnic backgrounds, we identified patterns of co-residence and
      investigated how and to what extent the likelihood of co-residence was influenced
      by migrant background, family ties, and the socio-economic characteristics of the
      family. The results show that of the four migrant groups, only Moroccan young
      adults are more likely than those of Dutch origin to live with their parents. For
      both migrant and Dutch young adults, family ties and the socio-economic
      characteristics of the family rather than an ethnic factor are the major
      influences on living arrangements.

PMID- 17558887
TI  - Is fertility indeed related to religiosity? A note on: 'marital fertility and
      religion in Spain, 1985 and 1999', Population Studies 60(2): 205-221 by Alicia
      Adsera.

PMID- 17558890
TI  - Evaluation of methods for trace-element determination with emphasis on their
      usability in the clinical routine laboratory.
AB  - Commonly used techniques for trace-element analysis in human biological material
      are flame atomic absorption spectrometry (FAAS), graphite furnace atomic
      absorption spectrometry (GFAAS), inductively coupled plasma atomic emission
      spectrometry (ICP-AES) and inductively coupled plasma mass spectrometry (ICP-MS).
      Elements that form volatile hydrides, first of all mercury, are analysed by
      hydride generation techniques. In the absorption techniques the samples are
      vaporized into free, neutral atoms and illuminated by a light source that emits
      the atomic spectrum of the element under analysis. The absorbance gives a
      quantitative measure of the concentration of the element. ICP-AES and ICP-MS are
      multi-element techniques. In ICP-AES the atoms of the sample are excited by, for
      example, argon plasma at very high temperatures. The emitted light is directed to
      a detector, and the optical signals are processed to values for the
      concentrations of the elements. In ICP-MS a mass spectrometer separates and
      detects ions produced by the ICP, according to their mass-to-charge ratio.
      Dilution of biological fluids is commonly needed to reduce the effect of the
      matrix. Digestion using acids and microwave energy in closed vessels at elevated
      pressure is often used. Matrix and spectral interferences may cause problems.
      Precautions should be taken against trace-element contamination during
      collection, storage and processing of samples. For clinical problems requiring
      the analysis of only one or a few elements, the use of FAAS may be sufficient,
      unless the higher sensitivity of GFAAS is required. For screening of multiple
      elements, however, the ICP techniques are preferable.

PMID- 17558891
TI  - Correlating purity by microdissection with gene expression in gastric cancer
      tissue.
AB  - Microdissection is a feasible tool for the purification of target cells from
      heterogeneous tissue components. However, the extent to which cells need to be
      purified by microdissection for use in gene expression analysis has not been
      determined. In the present study, we obtained diffuse-type gastric cancer tissues
      at varying purities, and evaluated the corresponding expression of a cancer
      specific gene, KRT19, by quantitative real-time PCR. The relationship between the
      degree of purity and gene expression was confirmed by using 60-mer
      oligonucleotide microarray analysis. Cancer-specific gene expression was stable
      in tissues of 10-50% purity, but at 60% or greater purity the slope of the graph
      was much steeper, indicating a correlation between tissue purity and increased
      gene expression. Tissues of 70% purity for cancer cells, acquired by
      microdissection, were therefore deemed to be of sufficient quality to distinguish
      between gene expression profiles from microdissected and non-microdissected
      specimens.

PMID- 17558892
TI  - Estrogen receptor-1 genotype is related to coronary intima thickness in young to
      middle-aged women.
AB  - OBJECTIVE: The incidence of coronary disease in premenopausal women is about one
      half that in men of similar age. The estrogen receptor-1 (ESR1, c.454-397T>C) CC
      variant genotype is associated with the severity of coronary artery disease (CAD)
      and an increased risk of myocardial infarction in men. The purpose of the present
      study was to investigate whether this ESR1 CC variant also disposes to
      atherosclerosis in women in terms of increased total coronary artery intima
      thickness. MATERIAL AND METHODS: A total of 125 forensic autopsy cases of women
      aged 15 to 49 years were investigated. The thickness of the coronary intima,
      which reflects the severity of atherosclerosis, was measured by computerized
      image analysis. The ESR1 c.454-397T>C genotype was determined by polymerase chain
      reaction (PCR). RESULTS: The mean intima thicknesses in the three genotype groups
      were 428+/-298 microm (TT), 494+/-371 microm (CT) and 636+/-436 microm (CC). We
      found that, on average, women with the CC genotype had a thicker coronary intima
      compared with that of women with the TT genotype, even after adjusting for age
      and body mass index (BMI) (p = 0.030). The intermediate group (TC) did not
      significantly differ from either the CC or the TT genotype group in this respect.
      CONCLUSION: Our results point to the importance of ESR1 genotype in relation to
      cardiovascular disease susceptibility.

PMID- 17558893
TI  - Maintained malnutrition produces a progressive decrease in (OPG)/RANKL ratio and
      leptin levels in patients with anorexia nervosa.
AB  - OBJECTIVE: Osteoprotegerin (OPG) and receptor activator of nuclear factor-kappaB
      ligand (RANKL) are key factors in bone remodeling in patients with anorexia
      nervosa (AN) and osteopenia. The purpose of this study was to investigate basal
      serum levels of OPG, RANKL and leptin, as well as bone mineral density (BMD)
      measured by DEXA at lumbar vertebrae L1-L4, and their evolution during one year
      in two groups of patients with AN. MATERIAL AND METHODS: Group I included 10
      adolescent girls suffering from malnutrition and secondary amenorrhea with an
      evolution of more than one year at the beginning of the study who received oral
      estrogen treatment throughout the follow-up period. Group II comprised 10 girls
      with malnutrition and secondary amenorrhea with an evolution of less than one
      year who received nutritional treatment only. All parameters were compared with
      those of a control group of 19 healthy, age-matched girls with normal BMI and
      regular menstrual cycles. RESULTS: The OPG/RANKL ratio was significantly
      decreased (p<0.05) after 1 year in group I, a fact that was due to an increase
      (p<0.05) in serum RANKL values. A correlation between OPG/RANKL and BMD was found
      in group I at the beginning of the study (r = 0.95; p<0.001). Patients in this
      group showed lower BMD values (p<0.01), both at diagnosis and at the end of the
      study, than those of group II patients, who showed normal BMD values. CONCLUSION:
      The decrease in the OPG/RANKL ratio in girls with AN could partly explain the
      increase in bone loss that occurs in these patients.

PMID- 17558894
TI  - Is flow cytometry really adapted to the determination of sperm concentration?
AB  - It has been reported that flow cytometry can be used as a reference procedure to
      determine sperm concentrations in quality control schemes in andrology
      laboratories, but there are no convincing quality control data. To understand
      comprehensively whether flow cytometry can be used to determine sperm
      concentration, sperm concentrations of 85 human semen samples were detected using
      three different methods, namely flow cytometry, computer-assisted semen analysis
      (CASA) and manual counting with a cell-VU chamber. The bead concentrations of
      both low [(18+/-2.5)x10(6)/mL] and high [(35+/-5)x10(6)/mL] pre-calibrated
      standard latex bead solutions were also determined with flow cytometry. The
      results showed that bead concentrations of both low and high pre-calibrated
      standard latex bead solutions counted five times with flow cytometry were
      (21.37+/-0.85)x10(6)/mL and (45.95+/-1.76)x10(6)/mL, respectively. Coefficient
      variances (CVs) and relative errors (REs) were 4%, 15.51% and 3.84%, 31.3% for
      low and high latex bead solutions, respectively. The overall correlation between
      values measured with flow cytometry and values measured with the cell-VU chamber
      and the CASA system was significant. However, flow cytometry overestimated the
      sperm concentration by 109% compared to the results with the cell-VU chamber.
      Moreover, for the azoospermic samples analysed, the sperm concentration was
      estimated at 0.12 (range from 0.04 to 0.24)x10(6)/mL. In conclusion, the data
      demonstrated that flow cytometry can result in an overestimation of both bead
      counting and sperm concentration, suggesting that flow cytometry is an
      inappropriate method for sperm counting, especially in the case of azoospermia.

PMID- 17558895
TI  - Borderline HER-2 breast cancer cases: histochemical versus real-time PCR analysis
      and impact of different cut-off values.
AB  - Seventy-one cases that had resulted borderline for HER-2 protein expression at
      conventional immunohistochemical assay (2+) were assessed for HER-2 gene
      amplification by real-time PCR and by FISH in accordance with the manufacturer's
      recommendations (gene amplification with ratio >or=2 in both methods). Thirty
      three out of 71 cases (47%) resulted amplified at real-time PCR analysis, whereas
      15 cases resulted positive at FISH (21%). Apparently, PCR was more sensitive than
      FISH in HER-2 determination, only 10 cases resulting amplified in both tests.
      When the mean ratio value obtained in all PCR experiments was adopted as
      threshold in determining HER-2 gene amplification, the apparent sensitivity of
      PCR was reduced but correlation between PCR and FISH results was dramatically
      increased. Furthermore, when the mean PCR ratio value observed in the FISH
      positive group was chosen as threshold, the best agreement between PCR and FISH
      results was achieved. Therefore, we found that the proposed threshold ratio value
      of >or=2 is not accurate in separating HER-2 amplified and non-amplified cases.
      We suggest that the threshold ratio value in PCR tests should be determined in
      each laboratory using FISH controlled cases. Finally, above certain in-lab
      generated threshold values, PCR might be proposed as a highly predictive positive
      test in HER-2 assessment.

PMID- 17558896
TI  - Repeatability of the measurement of augmentation index in the clinical assessment
      of arterial stiffness using radial applanation tonometry.
AB  - OBJECTIVE: Aortic augmentation index (AIx) measured using applanation tonometry
      is a non-invasive indicator of arterial stiffness. The objective of this study
      was to assess its repeatability when used by nurses with limited experience of
      the technique. MATERIAL AND METHODS: Blood pressure/augmentation index (BP/AIx)
      was measured 4 times in 20 consecutive ambulant patients (16 male) after they
      rested supine for 15 min. Two nurses independently and alternately measured
      BP/AIx using the same equipment (Omron HEM-757; SphygmoCor with Millar hand-held
      tonometer). Nurses were blinded to patient medical records and their colleague's
      AIx/BP. 'Within' and 'between' observer differences were assessed using intra
      class correlation coefficients (rI) and 95 % limits of agreement (95 % LoA)
      derived from Bland-Altman plots. RESULTS: Mean age was 56 (mean BP 136/79; mean
      pulse 64). Mean AIx was 24.1 (range 2.8 to 41.0). Both 'between' and 'within'
      observer repeatability was very high, with intra-class correlation coefficients
      ranging from 0.92 to 0.98. Mean AIx readings 'between' observers differed by only
      0.68 (95 % CI -0.24 to 1.59) with a high rI (0.98; 95 % CI 0.95 to 0.99) and a
      narrow 95 % LoA (-3.22 to 4.57). The 95 % LoA for 'within' observer repeatability
      was -6.75 to 7.95. Differences in AIx measurement did not vary over time or with
      increasing levels of AIx. CONCLUSIONS: Even when undertaken by relatively
      inexperienced operators, both 'within' and 'between' observer repeatability of
      AIx measurement is very high. Such non-invasive assessment of arterial stiffness
      has the potential to be included in the clinical assessment of ambulant patients.

PMID- 17558897
TI  - Elevated plasma glutathione peroxidase concentration in acute severe asthma:
      comparison with plasma glutathione peroxidase activity, selenium and
      malondialdehyde.
AB  - OBJECTIVE: To investigate plasma glutathione peroxidase concentration,
      glutathione peroxidase activity, plasma selenium and oxidative stress in acute
      severe asthma. MATERIAL AND METHODS: The study was case-control in design, with
      cases presenting to the emergency department with acute severe asthma and
      controls randomly selected from a larger cross-sectional study. Plasma
      malondialdehyde (MDA) was used as a measure of oxidative stress and plasma
      selenium was measured using ICP-MS. Glutathione peroxidase (GPx) activity was
      analysed using a colorimetric GPx assay and plasma GPx level was measured by
      enzyme-linked immunosorbent assay (ELISA). RESULTS: Fifteen cases [mean (range)
      predicted peak expiratory flow rate (PEFR) of 43% (20-69)] and 15 matched
      controls were recruited. MDA levels (mean+/-SD) were higher in acute asthma
      subjects (1.30+/-0.56 micromol/L) than in controls (0.86+/-0.53 micromol/L;
      p<0.05). There were no differences between cases and controls for selenium (99+/
      34 microg/L versus 109+/-17 microg/L) or for GPx activity (39+/-25 nmol min(-1)
      mL(-1) versus 38+/-24 nmol min(-1) mL(-1)), however, GPx plasma levels measured
      by ELISA were higher in cases than controls (22.5+/-10.8 mg/L versus 13.8+/-7.3
      mg/L; p<0.05). CONCLUSIONS: Patients with acute severe asthma demonstrated
      increased MDA levels but no differences in plasma selenium levels or GPx
      activity. GPx levels measured by ELISA were elevated in severe asthma. These
      results are consistent with an adaptive up-regulation of GPx to protect against
      oxidative stress.

PMID- 17558898
TI  - Determination of alpha-synuclein concentration in human plasma using ELISA.
AB  - The nerve cell protein alpha-synuclein is important in Parkinson's disease and
      dementia with Lewy bodies, and its expression levels are directly linked to
      development of the diseases. Quantification of the plasma level of alpha
      synuclein may therefore be important as a biomarker for disease susceptibility.
      We present a quantitative measurement of alpha-synuclein in the plasma of healthy
      control subjects in relation to their age using a novel enzyme-linked
      immunosorbent assay (ELISA). The plasma concentration among the 44 blood donors
      displayed a median of 5.6 microg/L (range 2.1-19.4 microg/L) with a narrow
      distribution (25 % and 75 % percentiles, 4.0 and 7.2 microg/L) and there was no
      correlation with age and gender. This narrow concentration range and the ease of
      measuring the quantitative ELISA support future investigations of plasma alpha
      synuclein in relation to neurodegenerative diseases.

PMID- 17558899
TI  - In search of an accurate and rapid method for sperm counting.

PMID- 17558901
TI  - Gastroesophageal reflux disease leads to major alterations in lectin-binding in
      the columnar epithelium of the gastroesophageal junction.
AB  - OBJECTIVE: Chronic gastritis and esophagitis are associated with changes in
      glycosylation patterns. Lectins are carbohydrate-binding proteins that are used
      as sensitive tools in the analysis of glycosylation patterns. The aim was to
      investigate the binding patterns of lectins UEA-I, DBA, HPA and PNA at the
      squamocolumnar junction in relation to the existence of gastroesophageal reflux
      disease (GERD) and Helicobacter pylori (H. pylori) infection. MATERIAL AND
      METHODS: Eighty-eight patients with either dyspeptic or gastroesophageal reflux
      related symptoms were included in the study and stratified into four subgroups
      based on the presence of GERD and H. pylori infection. The binding patterns of
      lectins were examined immunohistochemically at the squamocolumnar junction, in
      squamous (SE) and columnar-lined epithelium (CLE). Staining patterns of lectins
      were semiquantitatively evaluated using an immunohistochemical score; data were
      analyzed using the non-parametric Mann-Whitney U-test. RESULTS: The presence of
      GERD led to significant changes in lectin-binding patterns. Lectin-binding was
      significantly reduced for UEA-I (p<0.0001), DBA (p<0.0001), PNA (p<0.01) and DBA
      (p<0.05) in CLE and SE of patients with GERD, respectively. H. pylori infection
      was associated with reduced PNA and DBA binding to the deep glandular mucosa of
      CLE (p<0.05) and surface SE (p<0.05), respectively. CONCLUSIONS: Distinct and
      complex changes in lectin-staining patterns are most prominent in CLE of patients
      with GERD. The functional relevance of changes in the glycosylation patterns
      needs further investigation.

PMID- 17558902
TI  - Comorbidity and use of health-care services among irritable bowel syndrome
      sufferers.
AB  - OBJECTIVE: Patients suffering from irritable bowel syndrome (IBS) have more
      somatic and psychiatric comorbidity and use more health-care services for
      comorbid conditions than do other patients. Little is known about the frequency
      of comorbid symptoms among IBS sufferers in the general population and their
      influence on use of health-care facilities. The objective of this study was to
      compare the frequency of somatic and psychiatric symptoms between IBS sufferers
      and controls in the general population, and to study how comorbidity rates are
      distributed among consulters and non-consulters and how they predict the use of
      health care-services. MATERIAL AND METHODS: By means of a questionnaire sent to
      5000 randomly selected adults IBS was identified according to the Rome II
      criteria. The questionnaire also covered upper GI symptoms, non-GI somatic
      symptoms, depression and anxiety. A logistic regression analysis with 26
      variables was carried out to determine the independent predictors of health-care
      seeking for GI and non-GI complaints. RESULTS: The response rate was 73% and
      prevalence of IBS 5.1% (95% CI 4.4-5.8%). Dyspeptic symptoms, somatic extra-GI
      symptoms and psychiatric symptoms were reported by 45%, 69% and 51% of IBS
      sufferers, respectively, and 6%, 35% and 27%, of controls, respectively. Visiting
      a physician because of GI complaints was associated with disturbing abdominal
      symptoms, but not with depression or anxiety. Of the present GI conditions, only
      dyspeptic symptoms were associated with an increased consultation rate also for
      non-GI complaints. CONCLUSIONS: In the general population, both IBS consulters
      and non-consulters demonstrate high rates of comorbidity. Seeking health care for
      abdominal complaints is associated with abdominal symptoms rather than
      psychiatric comorbidity.

PMID- 17558903
TI  - Rectal distension inhibits postprandial small intestinal motor activity partially
      via the adrenergic pathway in dogs.
AB  - OBJECTIVE: Rectal distension is known to induce numerous upper gastrointestinal
      symptoms. The aim of this study was to investigate the effects and mechanisms of
      rectal distension on small intestinal myoelectrical and motor activities in 8
      dogs using a pair of intestinal electrodes and an intestinal fistula. MATERIAL
      AND METHODS: Experiment 1 entailed a 30-min baseline recording and a 30-min
      recording during rectal balloon distension at various volumes (60, 80, 100 and
      120 ml) randomly. Experiment 2 comprised three sessions, each including a 30-min
      baseline recording, a 20-min recording after intravenous infusion of saline,
      phentolamine (3 mg/kg) or propranolol (3 mg/kg), respectively, and another 30-min
      recording during rectal balloon distending. RESULTS: 1) Rectal distension
      resulted in reduced intestinal motility in a dose-dependent manner (r=0.68,
      p<0.001). 2) The reduction in intestinal motility was significantly diminished
      when infusions of phentolamine (2.7+/-1.0 versus 8.4+/-1.5, p<0.01) or
      propranolol (3.7+/-1.4 versus 8.4+/-1.5, p<0.05) were given, suggesting partial
      involvement of the alpha- and beta-adrenergic pathways. 3) Rectal distension did
      not affect the percentage of normal 17-22 cycles/min intestinal slow waves
      (97.5+/-2.5 versus 93.0+/-5.3, p>0.05), or their dominant frequency (17.2+/-1.2
      counts per minute (cpm) versus 17.7+/-1.0 cpm, p>0.05), or dominant power (-4.8+/
      2.5 versus -8.2+/-2.9 dB, p>0.05). CONCLUSIONS: Rectal distension inhibits
      postprandial small intestinal motor activity in a distension volume-dependent
      manner in dogs, and this inhibitory effect is at least partially mediated via the
      alpha and beta adrenergic pathways and does not involve any alterations in
      intestinal slow waves.

PMID- 17558904
TI  - Bone resorption is decreased postprandially by intestinal factors and glucagon
      like peptide-2 is a possible candidate.
AB  - OBJECTIVE: Food intake inhibits bone resorption by a mechanism thought to involve
      gut hormones, and the intestinotrophic glucagon-like peptide 2 (GLP-2) is a
      candidate because exogenous GLP-2 inhibits bone resorption in humans. The purpose
      of the study was to investigate patients with short-bowel syndrome (SBS) or total
      gastrectomy in order to elucidate whether the signal for the meal-induced
      reduction of bone resorption is initiated from the stomach or the intestine.
      MATERIAL AND METHODS: Bone resorption was assessed from the serum concentration
      of collagen type I C-telopeptide cross-links (s-CTX) and compared with the plasma
      concentrations of GLP-2. Bone formation was assessed from serum osteocalcin
      concentrations. Seven SBS patients with a preserved colon and 7 with SBS and
      colectomy and 7 healthy controls were given a breakfast test meal (936 kcal).
      Eight patients who had undergone total gastrectomy had an oral glucose load (75 g
      in 150 ml). RESULTS: The SBS patients without a colon showed no reduction in bone
      resorption (s-CTX) to a meal, whereas SBS patients with a colon had an
      intermediate response with a 27% (p<0.05) reduction of s-CTX from baseline after
      120 min as compared with 66% (p<0.001) for normal controls. A significant
      reduction of 53% (p<0.001) was seen in gastrectomized patients after receiving
      oral glucose, which is comparable with the published data for the oral glucose
      tolerance test (OGGT) in healthy subjects (50% reduction over 120 min). Bone
      formation was unchanged for both SBS and gastrectomy patients. GLP-2
      concentrations increased significantly in all groups with the exception of the
      SBS plus colectomy group. CONCLUSIONS: An intestinal factor is responsible for
      the postprandial reduction in bone resorption, and our findings are compatible
      with such a function for GLP-2.

PMID- 17558905
TI  - Anti-Saccharomyces cerevisiae antibodies in coeliac disease.
AB  - OBJECTIVE: To evaluate, retrospectively, the frequency of anti-Saccharomyces
      cerevisiae antibodies (ASCA) in patients with coeliac disease. MATERIAL AND
      METHODS: ASCA, IgG and IgA were determined by ELISA in sera of 238 coeliac
      patients. The patients were divided into three groups: group I - 125 untreated
      patients; group II - 42 patients under a strict gluten-free diet (GFD); and group
      III - 71 patients who did not comply with a GFD. Sera of 80 healthy blood donors
      served as controls. RESULTS: The frequency of ASCA (IgG or IgA) was significantly
      higher in untreated coeliac patients than in the control group (27.2% versus
      3.7%, p=10(-5)). In 238 coeliac patients, the frequency of ASCA was significantly
      higher in adults than in children (35.4% versus 21.1%, p=0.01). In group III, the
      frequency of ASCA was significantly higher in adults than in children (60% versus
      26.1%, p=0.004). In 238 coeliac patients, ASCA IgG were significantly more
      frequent than ASCA IgA in both children (19% versus 6.3%, p=0.001) and adults
      (33.3% versus 12.5%, p=5.10(-4)). In children, ASCA IgG were negative in group II
      and positive in 20% of group I (p=0.01). In adults, the frequency of ASCA IgG was
      also significantly lower in group II than in group I (9.5% versus 34%, p=0.03).
      CONCLUSIONS: A high frequency of ASCA has been found in coeliac patients. The
      frequency of ASCA was not statistically different between patients with
      successful adherence to GFD and healthy controls.

PMID- 17558906
TI  - Association of interleukin-1 receptor-associated kinase M (IRAK-M) and
      inflammatory bowel diseases.
AB  - OBJECTIVE: Inflammatory bowel diseases (IBD) have a complex genetic background.
      The interleukin receptor associated kinase-M (IRAK-M) is a NF-kappaB-mediated,
      negative regulator of Toll-like receptor (TLR) signaling. A functional mutation
      in a negative regulator might induce impaired endotoxin tolerance and increased
      inflammatory responses. IRAK-M is situated on chromosome 12q14, a susceptibility
      locus for IBD, which makes it a good candidate gene. The objective of the study
      was to analyze a large cohort of IBD patients for the association between IBD and
      IRAK-M. MATERIAL AND METHODS: A total of 542 patients with IBD (309 Crohn's
      disease (CD), 233 ulcerative colitis (UC)) and 305 controls were studied. Two
      single nucleotide polymorphisms (V147I and V270I) and six microsatellite markers
      were evaluated using association analysis and the haplotype sharing statistic.
      Results were stratified for CARD15 mutations R702W, G908R and 1007fsinsC.
      RESULTS: No significant differences in IRAK-M allele frequencies were observed
      between IBD, UC, CD or subgroups of CD or UC and controls. Five out of 36 UC
      patients (13.9%) with an IBD-associated CARD15 mutation were carriers versus
      2/167 (1.2%) in non-carriers (OR 13.1, 95% CI 1.0-164.5). No interaction was
      observed for CD. CONCLUSIONS: No evidence was found to suggest an association
      between IBD, CD, UC or subsets of CD and UC and IRAK-M. However, an interaction
      was found between IRAK-M and CARD15 in UC patients. In CARD15 mutant patients,
      the production of IRAK-M upon stimulation might be impaired. Further studies are
      needed to determine whether an impaired negative regulation of the TLR-signaling
      pathway might be partly responsible for the development of IBD.

PMID- 17558907
TI  - Treatment response and colonic gene expression in patients with Crohn's disease.
AB  - OBJECTIVE: Responses and adverse events to medication vary greatly among patients
      with Crohn's disease (CD). The aim of this study was to investigate whether
      global gene expression profiles could predict such responses and possible side
      effects. MATERIAL AND METHODS: Tissue specimens from the descending colon were
      obtained from 32 CD patients (in 18 patients from areas without inflammation and
      in 14 patients from inflamed areas). Gene profiling was done using the Affymetrix
      Human Genome U133 Plus 2.0 GeneChip array. Hybridization data were analyzed with
      dChip software. RESULTS: There were no differentially expressed genes between six
      patients who responded well to azathioprine and four who did not. No differences
      were found between 12 patients with adverse events to azathioprine and 9 patients
      who tolerated this drug. Sixteen patients who were not glucocorticoid-dependent
      had no differentially expressed genes as compared with 15 glucocorticoid
      dependent patients. Six patients who responded well to infliximab had only one
      differentially expressed gene as compared to four patients who did not.
      CONCLUSIONS: DNA microarray analyses did not show differentially expressed
      genetic profiles from colonic mucosal cells obtained from groups of patients
      classified according to therapeutic criteria.

PMID- 17558908
TI  - Comparison of outcome of POSSUM, p-POSSUM, and cr-POSSUM scoring after elective
      resection of the sigmoid colon for carcinoma or complicated diverticular disease.
AB  - OBJECTIVE: To compare POSSUM, p-POSSUM, and cr-POSSUM-predicted mortalities with
      the observed postoperative mortality in patients undergoing elective sigmoid
      colectomy for diverticular disease (n=121) or carcinoma (n=120). MATERIAL AND
      METHODS: The physiologic and operative severity score for the enumeration of
      mortality and morbidity (POSSUM) was used to identify patient- or disease-related
      risk factors and to calculate expected mortalities. RESULTS: Patients with
      carcinoma had significantly higher POSSUM scores, but the observed mortality
      (1.7%) was lower than that in the diverticular disease group (3.3%). In the
      carcinoma group, mortality was over-predicted by all the POSSUM systems. In
      diverticular disease, POSSUM over-predicted mortality while p-POSSUM and cr
      POSSUM under-predicted mortality. In the whole group, POSSUM over-predicted
      mortality. P-POSSUM and cr-POSSUM predicted mortality accurately:
      observed:expected (O:E) ratio 0.83. Replacing the score for malignancy with a
      minimum score of 1 gave overall O:E ratios of 0.37 (POSSUM), 1.04 (p-POSSUM), and
      0.93 (cr-POSSUM). CONCLUSIONS: In a group of patients who underwent elective
      resection of the sigmoid colon for carcinoma or diverticular disease,
      postoperative mortality was predicted accurately by p-Possum and cr-POSSUM,
      especially when used without a score for malignancy. None of the POSSUM scores
      were predictive of disease-specific mortality.

PMID- 17558909
TI  - Protein thiols and thiobarbituric acid reactive substance status in colon cancer
      patients.
AB  - OBJECTIVE: Colon cancer is the most common malignancy found in the developed
      countries. Cancer initiation and progression is known to be associated with the
      formation of reactive oxygen species, formed in excess in the gastrointestinal
      tract. The aim of the study was to assess the levels of protein thiols and
      thiobarbituric acid reactive substances (TBARS) in patients with colon cancer.
      MATERIAL AND METHODS; Serum samples were obtained from 60 subjects (M and F, mean
      age 50+/-15 years), 30 of which were from colon cancer patients and 30 from
      healthy individuals. All the serum samples were analyzed for carcinoembryonic
      antigen (CEA), protein thiols and TBARS. RESULTS: The levels of protein thiols
      were significantly lower in colon cancer patients (p<0.001) than in the healthy
      controls. The TBARS levels in colon cancer patients were moderately high (p<0.05)
      in comparison with those of the controls. CONCLUSIONS: Low levels of protein
      thiols and elevated TBARS of colon cancer patients support the hypothesis that
      colon cancer is associated with reactive oxygen species. Therefore protein thiols
      and TBARS may serve as additive non-invasive biochemical markers of oxidative
      stress in colon cancer and this hypothesis needs to be further investigated.

PMID- 17558910
TI  - Colonic expression of heme oxygenase-1 is associated with a better long-term
      survival in patients with colorectal cancer.
AB  - OBJECTIVE: Heme oxygenase-1 (HO-1) has emerged as a crucial mediator of mucosal
      defense in the gastrointestinal tract. Its metabolic pathway products,
      biliverdin/bilirubin and carbon monoxide, can reduce oxidative stress and
      inflammation, and promote resistance to apoptosis. The role of HO-1 in
      gastrointestinal malignancies, however, remains to be elucidated. The purpose of
      this study was to analyze HO-1 expression in human colon adenoma and cancer
      samples. MATERIAL AND METHODS: Fifty-five paraffin-embedded surgical specimens of
      colorectal cancer and 19 colonic adenoma samples were stained
      immunhistochemically for HO-1 expression using an anti-HO-1 monoclonal antibody.
      HO-1 expression was evaluated independently by two different investigators and
      subsequently correlated to clinical data and patients' life expectancy. RESULTS:
      Focal HO-1 expression could be documented in 41.8% (23/55) of patients with
      colorectal cancer. HO-1 expression in colonic adenoma was detectable in 36.8%
      (7/19) of cases. The rate of lymphatic tumor invasion was significantly lower in
      colorectal cancer samples expressing HO-1 (p=0.048). Additionally, fewer lymph
      node metastases were found in colorectal cancer samples with HO-1 expression, but
      these differences did not reach statistical significance. Mean observation period
      was 65.87+/-3.96 months. Kaplan-Meier analysis showed a significantly better
      survival for colorectal cancer patients with colonic HO-1 expression (p=0.018).
      CONCLUSIONS: This study demonstrates that colonic HO-1 may be a prognostic marker
      of colorectal-cancer outcome.

PMID- 17558911
TI  - Endoscopic mucosal resection of 161 cases of large sessile or flat colorectal
      polyps.
AB  - OBJECTIVE: Large sessile or flat colorectal polyps, which are traditionally
      treated surgically, may be amenable to endoscopic mucosal resection (EMR), often
      using a piecemeal method. Appropriate selection of lesions and a careful
      technique may enhance the efficacy of EMR for polyps >or=20 mm in diameter
      without compromising safety. The aim of this study was to identify the factors
      that may be predictive of the risk of polyp recurrence. MATERIAL AND METHODS: A
      retrospective analysis was conducted on the outcome of 161 polyps >or=20 mm in
      diameter, treated by piecemeal EMR at a single centre using the "lift and cut"
      technique. All records were reviewed for polyp size, site, morphology and
      histology. Polypectomy technique, patient follow-up, polyp recurrence and
      surgical interventions were also recorded. RESULTS: Over an 8-year period, 161
      colonic polyps measuring >or=20 mm were removed by EMR. Follow-up data were
      available for 149 cases (93%) with a mean polyp diameter of 32.5 mm; the total
      success rate of endoscopic polyp removal was 95.4%. The number of cases requiring
      1, 2, 3, 4 and 6 attempts at EMR was 89 (60%), 36 (24%), 14 (9%), 2 (1.3%) and 1
      (0.7%), respectively. Recurrence was significantly related to polyp size
      (p<0.001). There was no statistically significant relationship between site and
      recurrence. Seven patients (4.6%) underwent surgical intervention after EMR
      because of failed clearance. There were no post-EMR perforations and significant
      bleeding was reported in only two patients (1.7%). CONCLUSIONS: With careful
      attention to technique, piecemeal EMR is a safe option for the resection of most
      sessile and flat colorectal polyps >or=20 mm in size. A stricter follow-up may be
      required for larger lesions because of a higher risk of recurrence.

PMID- 17558912
TI  - Productivity improvements in hepatitis C treatment: impact on efficacy, cost,
      cost-effectiveness and quality of life.
AB  - OBJECTIVE: The treatment of chronic hepatitis C has advanced considerably during
      the past 15 years. The aim of this study was to evaluate the impact of different
      key developments from a health-economic perspective. MATERIAL AND METHODS: Costs
      and health-related quality-of-life data from a follow-up of Swedish patients
      treated for hepatitis C in clinical practice were used together with clinical
      trial data and natural history data in order to create a mathematical model that
      could be used to evaluate the advancement in hepatitis C therapy. The efficacy of
      treatment, costs and cost-effectiveness were evaluated for both current as well
      as proposed treatment strategies. A sensitivity analysis was used to assess how
      results were affected when key variables changed. RESULTS: Current genotype
      guided pegylated interferon and ribavirin is a cost-effective treatment strategy.
      A proposed treatment strategy involving a reduction in the length of treatment
      for certain patient subgroups with genotypes 1, 2 and 3, as well as an increase
      in the length of treatment for patients with genotype 1 and slow virological
      response was estimated to be a cost-effective future treatment alternative. These
      results were insensitive to changes in costs and risks associated with chronic
      hepatitis. CONCLUSION: Although the costs for treatment of hepatitis C have
      increased significantly over the past decade, the improvements have provided the
      health-care system with cost-effective options in the treatment of patients with
      chronic hepatitis C.

PMID- 17558913
TI  - Association between gallstone-evoked pain, inflammation and proliferation of
      nerves in the gallbladder: a possible explanation for clinical differences.
AB  - OBJECTIVE: To investigate whether enhanced neuroproliferation could be involved
      in the pathogenesis of gallstone pain. MATERIAL AND METHODS: Gallbladders from
      117 patients with gallstones and 43 controls were examined. The gallbladder
      samples were immunostained against the pan-neuronal marker PGP 9.5 and the number
      of nerves and nerve area per tissue area estimated. RESULTS: More nerves and an
      increased nerve area per tissue area were found in uncomplicated symptomatic
      gallstone disease. In comparison, acute cholecystitis displayed a significantly
      (p=0.01) decreased number of nerves and nerve area per tissue area. In both
      categories, the gallbladder neck contained more nerves (p=0.06 and 0.04,
      respectively) and an increased nerve area per tissue area (p=0.034 and 0.008,
      respectively) than the body. CONCLUSIONS: Uncomplicated disease showed enhanced
      neuroproliferation, significantly more in the gallbladder neck, whereas
      significantly fewer nerves were observed in acute cholecystitis. Nerve growth
      alteration may play a role in uncomplicated gallstone pain but the pathology may
      be different in inflammation.

PMID- 17558914
TI  - Improvement in caecal intubation rate and pain reduction by using 3-dimensional
      magnetic imaging for unsedated colonoscopy: a randomized trial of patients
      referred for colonoscopy.
AB  - OBJECTIVE: Use of magnetic endoscope imaging (MEI) during colonoscopy has the
      potential to ease caecal intubation and patient discomfort and to reduce
      dependence on sedation and/or analgesics (SAs). However, pain reduction by using
      MEI has not been demonstrated so far, probably because of the liberal use of SAs.
      The aim of the present study was to evaluate the effect of MEI on caecal
      intubation and patient pain during unsedated colonoscopy performed by experienced
      and inexperienced colonoscopists. MATERIAL AND METHODS: A consecutive series of
      outpatients referred for colonoscopy were randomly allocated to examination with
      (imager group) or without (standard group) the use of MEI. Patients agreeing to
      SAs being given only on demand were included in the study. End-points were caecal
      intubation and pain, the latter to be graded by category on a form to be
      completed on the day after the examination. RESULTS: The proportion of
      colonoscopies performed without SAs was similar when comparing imager and
      standard groups and experienced with inexperienced colonoscopists; altogether
      367(88%) out of 419 colonoscopies. The caecal intubation rate was higher in the
      imager group (190/212 (90%)) than in the standard group (153/207(74%)) (p<0.001),
      both collectively and separately for experienced and inexperienced
      colonoscopists. A pain-reducing effect of MEI was shown only when performed by
      experienced colonoscopists, with severe pain in 10/137 patients (7.3%) in the
      imager group and 21/132 patients (16%) in the standard group (p=0.03).
      CONCLUSIONS: In colonoscopy without the routine use of SAs, MEI significantly
      improves the caecum intubation rate and reduces pain during the procedure.

PMID- 17558915
TI  - Esophageal giant ulcer in primary human immunodeficiency virus infection is
      associated with an infiltration of activated T cells.
AB  - Primary human immunodeficiency virus (HIV) infection is a rarely diagnosed
      disease. The intestinal lymphocyte population represents a primary target of
      infection, virus replication, as well as cell infiltration and activation. The
      purpose of this study was to describe a patient suffering from esophageal giant
      ulcer as a clinical manifestation of primary HIV. In the present case of primary
      HIV infection a giant ulcer of the esophagus was diagnosed as the clinical
      manifestation. An upper endoscopy was performed and the biopsy specimens were
      further processed for immunohistochemical stainings characterizing the cellular
      infiltrate as well as cytokine production. In addition, seroconversion was
      documented and total viral load was determined. The esophageal ulceration
      presented the clinical manifestation of primary HIV infection since other causes
      of esophageal ulcerations could be excluded. The ulceration revealed an
      inflammatory infiltrate consisting of both CD4(+) and CD8(+) T cells. The vast
      majority of these cells expressed the activation marker CD38 and several cells
      showed interferon-gamma and interleukin-2 production. Furthermore, a substantial
      number of tissue infiltrating CD8(+) T cells expressed the cytotoxic molecule
      perforin. In addition, the HIV antigen p24 could be detected in the inflammatory
      infiltrate. Subsequent steroid treatment resulted in a relief of symptoms and
      healing of the ulcerations. These observations strongly suggest that infiltration
      of activated T cells plays a crucial role in the pathogenesis of giant ulcers
      during primary HIV infection.

PMID- 17558916
TI  - Is there an association between adult coeliac disease and non-specific abdominal
      pain?

PMID- 17558918
TI  - Temporal progression and extent of the return of sensation in the foot provided
      by the saphenous nerve after sciatic nerve transection and repair in the rat -
      implications for nociceptive assessments.
AB  - Sensory testing, by providing stimuli for nociceptors of the foot, is a popular
      method of evaluating sensory regeneration after damage to the sciatic nerve in
      the rat. In the following study, 20 rats were submitted to double transection of
      the sciatic nerve. The subsequent 14 mm gap was repaired through guidance
      interponation. In order to evaluate nerve regeneration, sensory testing was
      performed additionally to other methods, which included motor testing,
      morphometry, and electron microscopic assessments of nerves. Somatosensory
      testing revealed that all animals exhibited next to the same amount of sensory
      reinnervation on their foot regardless of their experimental group. In motor
      tests, however, two out of the three experimental groups did not improve at all.
      These groups also failed to show neural regrowth in morphometric and electron
      microscopic assessments of the associated nerve. Retrograde tracing was able to
      prove the saphenous nerve as an alternative source of sensory reinnervation in
      animals with failed sciatic regeneration. This means that results of sensory
      testing in the rat should be treated with caution, taking into account the areas
      tested and the likelihood that in these areas saphenous sprouting could have
      taken place. Furthermore, it is strongly advised that somatosensory testing
      should be conducted only on toe 5.

PMID- 17558919
TI  - The activation of the ERK pathway contributes to the spinal c-fos expression
      observed after noxious bladder stimulation.
AB  - C-fos is an immediate-early gene whose expression in the spinal cord has been
      extensively used as a marker of peripheral noxious stimulation. The Fos protein
      accumulates in the nuclei of spinal neurons, reaching detectable levels 2 h after
      stimulation. The ERK pathway is an important signalling pathway in spinal cord
      neurons. ERK is activated upon phosphorylation on specific amino acid residues.
      Its activation in the spinal cord, following noxious stimulation, has been shown
      to contribute to the establishment and maintenance of long-term neuronal
      alterations associated with chronic pain. Phosphorylated ERK can target several
      cellular elements, including transcription factors, which indicates that ERK
      participates in the regulation of gene expression. The relation between ERK and c
      fos is at present still unclear. Some in vitro studies have reached the
      conclusion that ERK contributes to c-fos regulation whereas others have provided
      evidence of ERK-independent c-fos expression. In fact, in the spinal cord the
      occurrence of c-fos expression in the absence of ERK phosphorylation has been
      reported. In this study we investigated in vivo the contribution of ERK to c-fos
      expression in the spinal cord. By inhibiting spinal ERK activation with
      intrathecal administration of PD98059, we verified that ERK phosphorylation does
      contribute to regulate c-fos expression upon noxious bladder stimulation.

PMID- 17558920
TI  - Tactile sensitivity of normal and autistic children.
AB  - Many children with autistic spectrum disorders have unusual reactions to certain
      sensory stimuli. These reactions vary along a hyper- to hypo-responsivity
      continuum. For example, some children overreact to weak sensory input, but others
      do not respond negatively to even strong stimuli. It is typically assumed that
      this deviant responsivity is linked to sensitivity, although the particular stage
      of sensory processing affected is not known. Psychophysical vibrotactile
      thresholds of six male children (age: 8-12) who were diagnosed to have autistic
      spectrum disorders and six normal male children (age: 7-11) were measured by
      using a two-alternative forced-choice task. The tactile stimuli were sinusoidal
      displacements and they were applied on the terminal phalanx of the left middle
      finger of each subject. By using a forward-masking paradigm, 40- and 250-Hz
      thresholds of the Pacinian tactile channel and 40-Hz threshold of the Non
      Pacinian I tactile channel were determined. There was no significant difference
      between the thresholds of autistic and normal children, and the autistic children
      had the same detection and masking mechanisms as the normal children. The sensory
      responsivity of each subject was tested by clinical questionnaires, which showed
      again no difference between the two subject groups. Furthermore, no significant
      correlations could be found between the questionnaire data and the psychophysical
      thresholds. However, there was a high correlation between the data from the
      tactile and emotional subsets of the questionnaires. These results support the
      hypothesis that the hyper- and hypo-responsivity to touch, which is sometimes
      observed in autistic spectrum disorders, is not a perceptual sensory problem, but
      may probably be emotional in origin.

PMID- 17558921
TI  - Limited transfer of podokinetic after-rotation from kneeling to standing.
AB  - Following stepping in place on a rotating treadmill, subjects inadvertently
      rotate when asked to step in place without vision. This response is called
      podokinetic after-rotation (PKAR). The purpose of this study was to determine
      whether PKAR transfers across tasks with different lower limb configurations,
      that is, from kneeling to stepping. We hypothesized that PKAR would transfer from
      kneeling to stepping for two reasons. First, there have been several
      demonstrations of robust PKAR transfer from forward to backward walking, stepping
      to hopping, running to walking, and from one limb to another. Second, we thought
      that afferent information regarding hip rotation was likely a key source of
      information to guide podokinetic adaptation and since hip rotation would be
      preserved in both stimulation conditions we expected to see little difference
      between the conditions. We compared the PKAR responses recorded in standing from
      13 healthy young volunteers after either standard stepping on a rotating
      treadmill or stepping while kneeling (kneel-stepping) on a rotating treadmill.
      Subjects performed two sessions of podokinetic (PK) stimulation, one stepping and
      one kneel-stepping on a rotating treadmill. Following the PK stimulation,
      subjects were blindfolded and asked to step in place in standing. Angular
      velocity of trunk rotation during PKAR from the two sessions was calculated and
      compared. The maximum angular velocities of PKAR recorded in stepping were
      significantly higher following the stepping session than following the kneel
      stepping session (9.10 +/- 8.9 and 2.94 +/- 1.6 deg/s, respectively). This was
      despite the fact that hip rotation excursion during PK stimulation was
      significantly greater in kneel-stepping (18.7 +/- 3.6 deg) than in stepping (12.2
      +/- 2.6 deg). These results indicate very little transfer from kneeling to
      stepping and suggest that afferent information regarding hip rotation is not the
      only or even the major source of limb position sense information used to drive
      locomotor trajectory adaptation.

PMID- 17558922
TI  - How proprioceptive impairments affect quiet standing in patients with multiple
      sclerosis.
AB  - To assess if multiple sclerosis patients with proprioceptive impairment are
      specifically affected during quiet standing with eyes open and how they can
      develop motor compensatory processes, 56 patients, classified from sensory
      clinical tests as ataxo-spastic (MS-AS) or only having spasticity (MS-S), were
      compared to 23 healthy adults matched for age. The postural strategies were
      assessed from the centre-of-pressure trajectories (CP), measured from a force
      platform in the eyes open standing condition for a single trial lasting 51.2 s.
      The vertical projection of the centre of gravity (CGv) and its vertical
      difference from the CP (CP-CGv) were then estimated through a biomechanical
      relationship. These two movements permit the characterization of the postural
      performance and the horizontal acceleration communicated to the CG and from that,
      the global energy expenditure, respectively. Both MS-AS and MS-S groups
      demonstrate larger CGv and CP-CGv movements than healthy individuals of the same
      age. Whilst similar CGv values are noticed in both MS subgroups, suggesting
      similar postural performances, statistically significant differences are observed
      for the CP-CGv component. Biomechanically, this feature expresses the necessity
      for the MS-AS group to develop augmented neuro-muscular means to control their
      body movements, as compared to the MS-S group. By demonstrating for both groups
      of patients similar postural performance accompanied by a varying degree of
      energy expenditure to maintain undisturbed upright stance, this study reveals
      that MS-AS patients which are affected by proprioceptive loss can compensate for
      this deficit with more efficient control strategies, when standing still with
      their eyes open.

PMID- 17558924
TI  - Individual differences in temperature perception: evidence of common processing
      of sensation intensity of warmth and cold.
AB  - The longstanding question of whether temperature is sensed via separate sensory
      systems for warmth and cold was investigated by measuring individual differences
      in perception of nonpainful heating and cooling. Sixty-two subjects gave separate
      ratings of the intensity of thermal sensations (warmth, cold) and nociceptive
      sensations (burning/stinging/pricking) produced by cooling (29 degrees C) or
      heating (37 degrees C) local regions of the forearm. Stimuli were delivered via a
      4 x 4 array of 8 mm x 8 mm Peltier thermoelectric modules that enabled test
      temperatures to be presented sequentially to individual modules or simultaneously
      to the full array. Stimulation of the full array showed that perception of warmth
      and cold were highly correlated (Pearson r = 0.83, p < 0.05). Ratings of
      nonpainful nociceptive sensations produced by the two temperatures were also
      correlated, but to a lesser degree (r = 0.44), and the associations between
      nociceptive and thermal sensations (r = 0.35 and 0.22 for 37 and 29 degrees C,
      respectively) were not significant after correction for multiple statistical
      tests. Intensity ratings for individual modules indicated that the number of
      responsive sites out of 16 was a poor predictor of temperature sensations but a
      significant predictor of nociceptive sensations. The very high correlation
      between ratings of thermal sensations conflicts with the classical view that
      warmth and cold are mediated by separate thermal modalities and implies that warm
      sensitive and cold-sensitive spinothalamic pathways converge and undergo joint
      modulation in the central nervous system. Integration of thermal stimulation from
      the skin and body core within the thermoregulatory system is suggested as the
      possible source of this convergence.

PMID- 17558923
TI  - Texture perception through direct and indirect touch: an analysis of perceptual
      space for tactile textures in two modes of exploration.
AB  - Considerable information about the texture of objects can be perceived remotely
      through a probe. It is not clear, however, how texture perception with a probe
      compares with texture perception with the bare finger. Here we investigate the
      perception of a variety of textured surfaces encountered daily (e.g., corduroy,
      paper, and rubber) using the two scanning modes - direct touch through the finger
      and indirect touch through a probe held in the hand - in two tasks. In the first
      task, subjects rated the overall pair-wise dissimilarity of the textures. In the
      second task, subjects rated each texture along three continua, namely, perceived
      roughness, hardness, and stickiness of the surfaces, shown previously as the
      primary dimensions of texture perception in direct touch. From the dissimilarity
      judgment experiment, we found that the texture percept is similar though not
      identical in the two scanning modes. From the adjective rating experiments, we
      found that while roughness ratings are similar, hardness and stickiness ratings
      tend to differ between scanning conditions. These differences between the two
      modes of scanning are apparent in perceptual space for tactile textures based on
      multidimensional scaling (MDS) analysis. Finally, we demonstrate that three
      physical quantities, vibratory power, compliance, and friction carry roughness,
      hardness, and stickiness information, predicting perceived dissimilarity of
      texture pairs with indirect touch. Given that different types of texture
      information are processed by separate groups of neurons across direct and
      indirect touch, we propose that the neural mechanisms underlying texture
      perception differ between scanning modes.

PMID- 17558925
TI  - Possible glutaminergic interaction between the capsule and neurite of Pacinian
      corpuscles.
AB  - The role of the capsule encasing the Pacinian corpuscle's (PC's) neurite, where
      mechanotransduction occurs, may be more than mechanical. The inner core of the
      PC's capsule consists of lamellar cells that are of Schwann-cell origin.
      Previously, we found both voltage-gated Na+ and K+ channels in these inner-core
      lamellae. Research on astrocytes and Schwann cells shows bidirectional signaling
      between glia and neurons, a major component of which is glutamate. Furthermore,
      Merkel cells show positive immunoreactivity for glutamate receptor mGluR5, and
      the glutamate-receptor antagonist kynurenate greatly decreases the static
      activity of the slowly adapting neurons of Merkel cell-neurite complexes. To
      investigate the possibility of glutaminergic interaction in PCs, we applied
      antibodies to glutamate, glutamate receptors, glutamate transporters, and SNARE
      proteins to cat mesenteric PC sections. Positive labeling was seen in the inner
      core lamellae, at inter-lamellar connections, where the lamellae contact the
      membrane of the neurite and at the lamellar tips. The presence of these proteins
      on the lamellae and neurite membranes, demonstrated both with immunofluorescent
      light microscopy as well as immunogold electron microscopy, suggests a chemical,
      possibly bidirectional, interaction between the lamellar cells and the neurite.
      Thus, the capsule of the PC, apart from having a mechanical filtering function,
      may also provide an environment for lamellar-neurite interaction, perhaps acting
      as a neuro-modulator of the initiation, and/or continuation, of the mechanical
      electrical transduction process. At the very least, the presence of the
      aforementioned proteins suggest some sort of "synaptic-like" activity in these
      mechanoreceptors, which up until now has not been considered possible.

PMID- 17558926
TI  - Proceedings from the 8th Annual Middle Eastern Mediterranean Summer Institute on
      Drug Use (MESIDU), February 13-18, 2004, Italy.

PMID- 17558927
TI  - Measuring levels of comorbidity in drug user* emergency patients treated in
      Ontario hospitals.
AB  - We examined the nature and extent of health problems in drug user patients
      initially treated in emergency departments and who were subsequently admitted to
      all hospitals in Ontario, using data from the Hospital Medical Records Institute
      (HMRI). The modified standardized morbidity ratio (modified SMR) is introduced to
      improve the measurement and visual display of reduced morbidity as well as excess
      morbidity. During 1985-86, about 75% of drug user patients entered hospital
      through the emergency department. There were 5077 emergency patients with primary
      drug use-related diagnoses and 9827 with secondary drug use-related diagnoses.
      Cases with poisoning diagnosis made up over 80% of all drug use cases treated in
      emergency departments. Cases with non-dependent abuse of drugs accounted for 8
      12% of emergency drug user patients, whereas those with drug dependence accounted
      for about 3% of emergency drug user patients. These patients had more than three
      times the comorbidity experience of all hospital patients. They had excess
      comorbidity due to mental disorders, infectious and parasitic disorders, and
      injury and poisoning diagnoses. However, they had reduced comorbidity due to
      complications of pregnancy, childbirth, and the puerperium and from congenital
      anomalies and conditions originating in the perinatal period. Cocaine patients
      were more likely to have infectious parasitic diseases and diseases of the skin
      and subcutaneous tissue, while amphetamine patients were more likely to have
      diseases of the digestive system and of the musculo-skeletal system and
      connective tissue.

PMID- 17558928
TI  - Suffering, choice, and freedom.
AB  - This article attempts to describe illness as a comprehensive individual
      experience quoting both sacred texts and writings of famous authors. Illness
      needs the concepts and the practices of soul, spirit, and meaning, which are the
      counterparts of the current medical notion of bodily and mental processes. In
      their absence, even the relationship from clinician and client transforms itself
      into a hopeless and compulsive interaction. Illness affects both feeling and
      thoughts in an unpredictable way and may allow an individual to rise through
      spiritual pathway it implies. The passage between pain and suffering toward the
      experience of freedom occurs by means of dark or even desperate moments, when
      active listening to the person in need and the operation of a Higher Power are
      necessary opportunities. Health professionals, nowadays in favor of medical
      technology and of the actions oriented to fighting the disease, may develop a
      therapeutic communication with their patients in order to help their
      understanding of the meaning that their illness has at the end for themselves.

PMID- 17558929
TI  - Drug courts - just the beginning: getting other areas of public policy in sync.
AB  - Although an offender can complete a drug court program in the United States, have
      his/her charges dismissed or reduced (or some other amelioration of the criminal
      justice system penalty that would otherwise have been applied), become drug free,
      obtain a job, regain custody of his/her children, become a tax-paying, law
      abiding citizen, etc., he/she will still be deprived of basic rights afforded to
      other U.S. citizens because other sectors of public policy still approach
      addiction with a punitive orientation. Thus, despite the fact that an offender
      may have made a substantial beginning in recovery, other parts of the system make
      no accommodation for his/her recovery efforts in, for example, their denial of
      (a) welfare benefits to persons charged/convicted of drug offenses; (b)
      educational loans or other benefits to persons charged/convicted of drug
      offenses; (c) public housing to persons charged/convicted of drug offenses; and
      (d) voting rights to persons with felony convictions. In addition, deportation
      proceedings can be instituted - even for persons with a legal immigration status 
      based upon a charge or conviction for a drug offense. Without changes in other
      key areas of public policy, the goals and benefits designed to be achieved by the
      criminal justice system through drug court programs can be thwarted in both the
      short and long term by the failure of a shift in thinking in other key public
      sector areas that are critical to meaningfully reintegrating substance-addicted
      offenders into the mainstream of the community. Hopefully, policy-makers will
      begin to address this critical need.

PMID- 17558930
TI  - Harm and risk reduction: history, theories, issues, and implications.
AB  - Harm reduction is explored, historically, in terms of ideologies, concepts,
      processes, types, stakeholders, legal, policy, service delivery, and ethical
      considerations and their micro and macro consequences. Necessary critical
      conditions underpinning ideologies and programs throughout their life cycle are
      examined, as are selected unresolved issues and paradoxes. Importantly, harm
      reduction can inadvertently result in distancing drug users (DUs) from mainstream
      ("normed") care by institutionalizing specialized care for DUs who remain
      "marginalized" from the community at large. Also, harm reduction can become harm
      production when program staff, who should be foster autonomy and self-care in
      partnership with DUs, are co-opted into becoming social control agents acting on
      compliant, passive, pathologized, and dehumanized stereotypes - Them.

PMID- 17558931
TI  - Technology transfer from the science of medicine to the real world: the potential
      role played by artificial adaptive systems.
AB  - The author describes a refiguration of medical thought that originates from
      nonlinear dynamics and chaos theory. The coupling of computer science and these
      new theoretical bases coming from complex systems mathematics allows the creation
      of "intelligent" agents capable of adapting themselves dynamically to problems of
      high complexity: the artificial neural networks (ANNs). ANNs are able to
      reproduce the dynamic interaction of multiple factors simultaneously, allowing
      the study of complexity; they can also draw conclusions on an individual basis
      and not as average trends. These tools can allow a more efficient technology
      transfer from the science of medicine to the real world, overcoming many
      obstacles responsible for the present translational failure. They also contribute
      to a new holistic vision of the human subject person, contrasting the statistical
      reductionism that tends to squeeze or even delete the single subject, sacrificing
      him to his group of belongingness. A remarkable contribution to this individual
      approach comes from fuzzy logic, according to which there are no sharp limits
      between opposite things, such as wealth and disease. This approach allows one to
      partially escape from the probability theory trap in situations where it is
      fundamental to express a judgement based on a single case and favor a novel
      humanism directed to the management of the patient as an individual subject
      person.

PMID- 17558932
TI  - Cultural-level influences on substance use & misuse.
AB  - This presentation discusses potential associations between dimensions of culture
      and patterns of substance use. Several well-known frameworks for organizing
      cultural values and orientations are presented. As an illustration, one framework
      (Hofstede, 2001) is examined for its relevance in understanding national-level
      variations in patterns of alcohol and illicit drug use. Two of four cultural
      dimensions examined, individualism-collectivism and uncertainty avoidance, are
      found to be independently associated with one or more substance use measures in a
      diverse sample of 64 nations. Future multi-level analyses that integrate cultural
      values and orientations into empirical studies will enable more systematic
      assessments of the role of socio-cultural contexts in substance use epidemiology.

PMID- 17558933
TI  - An example of international drug politics--the development and distribution of
      substance prevention programs directed at adolescents.
AB  - Many substance use prevention programs directed at adolescents exist that have
      been developed by researchers in the United States and are intended to be used in
      school settings. Some of the problems associated with such programs are reviewed,
      including their accessibility, ease of use, copyright status, evaluation options,
      program scales, and ratings, together with an overall consideration of the
      factors and processes posited to be associated with substance use and non-use
      (posited "at-risk" and "protective" mechanisms). The authors contend that there
      is a great need to: (a) develop substance use prevention programs which are
      commercially available but are not protected by copyright, (b) assess empirically
      each component in a program separately, and (c) encourage funding bodies to be
      more active in supporting the production of manuals and evaluation instruments
      for substance use prevention programs directed at adolescents. We need more and
      better process evaluations that are also sensitive to both endogenous and
      exogenous forces in order to know the processes by which a successful prevention
      program achieves its effects, is prevented from doing so and which processes are
      irrelevant. A social competence framework might be used as both a goal and as a
      theoretical base to achieve a better understanding of the processes by which
      substance use prevention programs reach their effects.

PMID- 17558934
TI  - The relationship between substance user treatment and 12-step fellowships:
      current knowledge and research questions.
AB  - This article reviews and synthesizes information about the relationship between
      two distinct approaches to helping substance users, formal "addiction treatment"
      and 12-step mutual aid. The following issues are addressed: Extent of formal
      treatment and 12-step fellowship participation for persons with substance use
      related problems; overlap between treatment and 12-step participation; early
      attempts to "integrate" treatment and 12-step mutual aid; differences and
      similarities between the 12-step program and treatment; issues of spirituality in
      the 12-step program; effectiveness of 12-step participation as treatment
      aftercare; and whether help-seekers can be "matched" to 12-step. The article
      poses pertinent questions that could answered by additional research, including
      life cycle patterns of usage of treatment and 12-step, outcomes of such episodes,
      reasons for using different interventions at different times, feasibility of 12
      step participation as a primary intervention, the relative contributions of
      striving for spiritual values vs. social support factors to the effectiveness of
      12-step, and the comparative effectiveness of secular vs. 12-step mutual aid. The
      article concludes with a proposed reconceptualization of the relationship between
      formal treatment and 12-step mutual aid that may help in structuring future
      research.

PMID- 17558935
TI  - Age differences in lesbian identity development and drinking.
AB  - Women who "come out" as lesbian must learn to cope with a stigmatized identity.
      Stress associated with the sexual identity development process is a commonly
      posed explanation for the high rates of "heavy drinking" and drinking consumption
      related problems within this population. However, relatively little is known
      about the sexual identity development process in lesbians and even less about
      lesbians' drinking patterns during this process. Growing societal tolerance and
      visibility of sexual minorities over the past 35 years has likely created
      substantially different environments and experiences of coming out for
      individuals of different age cohorts. Data from the Chicago Health and Life
      Experiences of Women study provided the opportunity to examine relationships
      between variables associated with lesbian identity development and alcohol use
      related problems in three age cohorts of self-identified lesbians. The study's
      limitations are noted.

PMID- 17558936
TI  - Resilience in children of substance users: in their own words.
AB  - Understanding what children of alcoholics and other substance users experience
      has dominated the scientific literature and popular press for the past several
      decades. To date, the empirical studies have relied primarily on quantitative
      data to understand the individual and environmental factors associated with the
      lives, the developmental trajectories, and the growth of children of alcoholics
      and other substance users. Many of these studies focus on their risks, and very
      few of them focus on their strengths. Additionally, very few studies have used
      qualitative techniques to collect data. While quantitative studies have given us
      great insight, perhaps we could learn a great deal more if we employed data
      collection methods which would actually provide us with the child's perception of
      their strengths, or resilience, and what they think it takes to grow into happy,
      healthy adults. For this reason, this study presents data from the interviews of
      50 children of substance users who present their views on resilience.

PMID- 17558937
TI  - The specter of shame in substance misuse.
AB  - This article provides an introduction to the concept of shame as it relates to
      substance misuse. Empirical research on shame and addiction and the theoretical
      and operational definitions that underpin them are discussed. Potential areas of
      further inquiry are highlighted. Implications for clinical practice are
      discussed.

PMID- 17558938
TI  - Museum exhibit guidelines "addictions" - money - stakeholders - power in Western
      society.

PMID- 17558939
TI  - Florence: one month later.
AB  - A reflection on time spent in Florence which precipitated memories of an
      extraordinary woman whom the author had met during her first year or professional
      nursing. In this essay the author introduces the reader to the work of Carol
      Bowman, an imaginative scholar who created a bridge which spanned the study of
      humanities and the treatment of addictions.

PMID- 17558940
TI  - Addiction, risk, and resources.
AB  - Addiction is a contemporary social issue bound to the myth of self-control and
      control of the other, which is typical of the contemporary "market ideology"
      society. In its broad definition it includes not only the use and misuse of
      "substances" and addictive behaviors, but also the concept of risk. There is a
      continuum between "addicted behaviors" and behaviors that are not "addicted" but
      may induce and/or be related to both physical and psycho-social problems on a
      micro- to macrolevel. Different studies have documented substantial changes in
      the consumption of tobacco, drugs, alcoholic beverages, as well as "junk foods"
      during the last decades in various countries. All too often politicians, health
      administrators, and local providers believe that consumption prevention programs
      are able, per se, to effect such changes. In fact, the impact of factors such as
      international trade, globalization and societal values, among many others, are
      considered relevant. On the other hand, sufficient place must be given to
      national and community-based preventive initiatives.

PMID- 17558942
TI  - Traditional and other drug use(r) intervention: necessary critical parameters.
AB  - The presentation consisted of a number of pages listing major area topic headings
      and subheadings, some of which were further delineated. Its purpose was to serve
      as a framework and a guide for the exhibit's planning in order to help the
      visitor to actively consider: The complexity and multi-dimensionality of
      substance use and its interventions, past, present and future (both more
      immediate and more distant) in terms of areas, processes, models, stakeholders,
      and unresolved critical issues. That the traditional view that considering and
      understanding (a) types of drugs and their actions, (b) types of users and their
      focused-on characteristics and behaviors (and not their actual as well as
      potential strengths and limitations), and (c) some of the semantics of the field
      are sufficient for effective intervention, has resulted and will continue to
      result in built-in failures and unnecessary frustrations for a range of
      individuals (substance users and non-users) and systems. The dimensions of what
      is being focused on, their "demands," and the critical necessary conditions
      (endogenous and exogenous) for a posited concept, process, model, policy, etc.,
      to operate (begin, continue, become integrated and anchored, change as realities
      change, etc.) or not to operate. What interests and whose interests have been
      served and which need to be served with and through substance use(r) intervention
      and/or non-intervention; who and what are the facilitators-promoters; barriers
      preventers, as well as irrelevant foci that can and do use up limited
      intervention resources (human and non-human resources).

PMID- 17558944
TI  - The female drug user: risk factors and prejudices.

PMID- 17558945
TI  - The healing forest metaphor revisited: the seen and "unseen world" of drug use.
AB  - There is one world we live in. Its geographical and spatial boundaries tell us
      this. We see it on maps, we see it on television, and we see it when we walk out
      of the door. Children, adults, and people of all races and creeds live in this
      one world. The world we live in is viewed differently by these many individuals.
      Some see it as hostile, some see it as peaceful, and some go about their daily
      business and do not see it at all. This is the seen world. The one we can see
      with our eyes. The seen world is not the only one that exists, however, because
      there is also another world behind our eyes. When we close our eyes, it is in
      there. We have an imagination to tell us what it could be like, we have thoughts
      to tell us what we want it to be like, and we have dreams to tell us what we want
      it to be. Where is this unseen world? We carry it around with us every nanosecond
      of every day that we are alive. While we live in the seen world, the unseen world
      is alive in us. What could the unseen world be like for substance users? This is
      the topic of the current article.

PMID- 17558946
TI  - How cultural factors influence school-based substance use prevention programs.
AB  - This article analyzes school-based substance use prevention programs, comparing
      programs in the United States and Nordic countries, explores how cultural factors
      influence the ways in which prevention programs are designed and implemented, and
      how evaluation is affected by design and implementation.

PMID- 17558947
TI  - Drug prohibition and the treatment system: perfect together.
AB  - The "War on Drugs" in the U.S. is consistent with the predominance of the
      abstinence model for treatment and helps legitimate compulsory treatment.
      Alternative public health approaches such as harm reduction are suspect and
      devalued. The mission of treatment risks becoming trivialized, primarily focusing
      on separating individuals from "illicit" psychoactive substances, in perfect
      accord with current drug policy. The current policy breeds disrespect for law and
      imposes enormous social and economic costs on society, without demonstrable
      effects on the availability or costs of "illicit" drugs. Maintaining the policy
      has become an end in itself, as shown in the disproportionate campaign against
      marijuana use, but there are signs that the policy is becoming vulnerable.
      Similarities to the situation at the time of the repeal of alcohol prohibition in
      1933 are discussed.

PMID- 17558948
TI  - The habitual brain: an "adapted habit" theory of substance use disorders.
AB  - Behavioral habits are essential to human and animal life. We consider the many
      ways that habits - which are normally adaptive - can be expressed as drug use
      behavior and addiction. Although habit theories of substance use disorders have
      been proposed (e.g., Tiffany, 1990), the behavioral science and underlying
      neurobiology of habit development, maintenance, and change is only now being
      studied. We first define "adapted habit." We then propose that the etiology of an
      adapted habit represents the combination of: (a) initial "capture" of a habit,
      (b) development of behavioral action schemata, and (c) an overlay of cognitive
      expectancies concerning aspects of the habit. This combination conspires to make
      an intractable adapted habit such as substance abuse and addiction. Many
      intractable habits change, including substance use disorders such as cigarette
      smoking. As part of a science of habits, we need a real understanding of how to
      change habits to avoid or minimize harm.

PMID- 17558949
TI  - Trauma and substance misuse: critical considerations in understanding the
      maelstrom.
AB  - Research has established that a relationship between trauma and substance use
      disorders (SUDs) exists. The nature of the relationship and its dimensions are
      not well understood. Nevertheless, it is important to consider either problem
      when the other is present. Given the spate of traumatic events occurring globally
      in recent years, it is critical for the planning group for the development of the
      "For Whom Is It Permitted, for Whom Is It Forbidden" museum exhibit to consider
      the complex relationship between trauma and SUDs and ways of representing it in
      the exhibit. This article briefly discusses what is posited and known about
      trauma and SUDs in relation to one another. Key points to consider in developing
      representations of the relationship between trauma and SUDs are raised.

PMID- 17558950
TI  - A museology display: questioning and answering.
AB  - The process of a museology display and experience is presented.

PMID- 17558952
TI  - Prevalence of American Indian adolescent tobacco use: 1993-2004.
AB  - Tobacco use rates for American Indian adolescents are examined and compared to
      rates for non-Indian youth. The data are taken from an ongoing surveillance
      project of substance use among Indian youth and the Monitoring the Future Project
      for the years 1993 to 2004. Sample sizes are in the range of 14,000 to 17,000 for
      non-Indian youth and 600 to 2400 for Indian youth. Tobacco use is considerably
      higher for Indian youth; however, these rates are following the national trends
      of significant reductions over the past three years. Indian youth manifested a
      lower perception of harm from regular tobacco use, which may, in part, account
      for their higher levels of use. Indian females have had slightly higher rates of
      lifetime and daily smoking rates than males in the past but recent trends
      indicate a narrowing of this gap.

PMID- 17558953
TI  - Using a community readiness model to help overcome breast health disparities
      among U.S. Latinas.
AB  - The aim of this article is to illustrate how investigators can use a strength
      based model, such as the Community Readiness Model (CRM), to help overcome breast
      health disparities among Latinas living in the United States. In this effort, I
      describe a CRM study conducted between the years 2001 and 2002 in four
      predominantly Latino communities in Colorado. First, 19 key informants were
      interviewed to assess their perceived level of community readiness to encourage
      Latinas participation in breast cancer prevention and control activities. Next,
      33 Latinas over the age of 50 participated in focus groups to further examine
      perceptions of barriers and facilitative factors to participate in the
      activities. Lastly, 14 one-on-one interviews were conducted to clarify and expand
      on the information provided by key informants and focus group participants. We
      bridged this research to practice by creating and testing (with 22 Latinas)
      breast health educational materials that address in a culturally sensitive manner
      Latinas' main concerns about participating in these lifesaving activities.

PMID- 17558954
TI  - Cultural traditions as "protective factors" among Latino children of illicit drug
      users.
AB  - Family bonding was examined among Hispanic adolescents whose fathers are illicit
      drug users to ascertain whether such adolescents maintain close affective family
      ties or alienate themselves from their families given their father's use of
      illicit drugs and referral to a drug screening and treatment program. It was
      hypothesized that high levels of paternal drug use would be associated with the
      youth's alienation from the family. In addition, it was postulated that the
      adolescent's endorsement of traditional cultural values and social responsibility
      would protect her or him against this effect in relation to family bonding. These
      hypotheses are based on prior research that suggests that youth bonding to
      prosocial institutions, such as family, school, church, and community
      organizations, can be "protective" against drug use. More specifically, our
      analyses examined the role of level of acculturation in middle school, family
      traditionalism, American orientation, Latino orientation, and social
      responsibility in predicting adolescents' family bonding. Results indicated that
      the father's level of marijuana and/or methamphetamine use was unrelated to youth
      family bonding. Additionally, Latino and American cultural orientations and level
      of acculturation in middle school were not associated with family bonding. By
      contrast, social responsibility (the youth's citizenship and responsibility to
      the community) and family traditionalism (endorsing conservative cultural values
      regarding the maintenance of family traditions and respect for elders and family)
      were significantly associated with family bonding. In other words, among children
      of Latino illicit drug users, the youth's conservative family values and a
      responsible attitude toward community traditions were dual factors related to
      family bonding, perhaps operating also as sources of "protection" against youth
      problem behaviors.

PMID- 17558955
TI  - Disparities in young adolescent inhalant use by rurality, gender, and ethnicity.
AB  - Inhalant use is of increasing concern as rates appear to be rising among young
      adolescents and gender differences narrowing. Data from 20,684 Mexican American
      and White non-Hispanic seventh- and eighth-grade males and females from the
      Western United States and 15,659 African American and White non-Hispanic seventh-
      and eighth-grade males and females from states in the southeastern United States
      collected via in-school surveys from 1996 to 2000 were analyzed using a variety
      of statistical techniques including multilevel modeling. Questions addressed in
      the study included: Does inhalant use vary by level of rurality? What effect does
      the ethnic composition of the community have on inhalant use and does this effect
      differ by an individual's ethnicity? Do males use more inhalants than females and
      does the level of use by males and females differ by individual ethnicity,
      ethnicity of the community, or level of rurality? Do males and females of
      different ethnicities initiate inhalant use at different ages? Limitations of the
      study and implications of findings for prevention are discussed and areas of
      future research are suggested. This study was funded by the National Institute on
      Drug Abuse.

PMID- 17558956
TI  - Substance use(r) treatment and health disparities: some considerations or an
      askance look at institutionalized substance use(r) intervention disparities.
AB  - It is necessary to consider substance user treatment and derived health
      disparities in terms of: historical perspectives, stereotyping and
      "homogenization"; mystification; institutionalized disinformation; institutional
      myopia; institutionally created and maintained paradoxes; organizational,
      systemic, and human failure; the status of facts; environmental considerations;
      conceptual masking and overloading; fictions and fantasies; policy models and
      policy perversion; resource ignorance; slogans; de facto realities; the
      phenomenon of "lifeless lucidity" when statistical significance is not matched by
      substantive significance, problem definitions, and current unresolved critical
      issues that merit attention. The article's central thesis is that substance user
      treatment failure and derived health disparities are built into this complex,
      chaotic, nonlinear, multidimensional, highly politicalized, arbitrary, but
      institutionalized and "ghettoized" field that is also faulted by human, systemic,
      and organizational errors and that is removed from the "normed," mainstream of
      intervention and innovation.

PMID- 17558957
TI  - Proceedings "strength-based models to overcome disparities: bridging research to
      practice," a conference held at the Tri-Ethnic Center for Prevention Research,
      Colorado State University, Fort Collins, CO, September 9 and 10, 2002 culture and
      health disparities.

PMID- 17558958
TI  - Strength modeling: the role of data in defining needs and response for American
      Indian substance users.
AB  - Essential to clarifying the nature of health disparities and ultimately to
      developing appropriate responses is the access and availability of accurate,
      relevant data. This need is particularly obvious at the level of public health
      policy and practice. Unfortunately, current data sources are frequently
      restricted by a variety of factors, including jurisdictory limitations that
      restrict exchange of information between health delivery systems. This study was
      conducted to review conclusions drawn from disparate, yet functionally
      interdependent, data sources regarding alcohol-related medical outcomes among
      American Indians; specifically, non-reservation-residing Indian people. Data were
      collected from 1998 to 1999. The comparison revealed critical inconsistencies
      between data sources, reinforcing the call for enhanced data exchange and caution
      in interpreting data from singular sources.

PMID- 17558959
TI  - "The left hand does not know what the right hand is doing": rural and urban
      cultures of care for persons with traumatic brain injuries.
AB  - This qualitative study examined systems of care for individuals with brain
      injury, from the providers' perspective, in two Colorado communities, one rural
      and one small urban, from 1998 to 2001. Using a guided interview format the
      researchers interviewed 53 medical, rehabilitation, community, and school service
      providers in the two sites. Of the 53 providers, ethnicity was reported as 100%
      Caucasian. Client ethnicity in the rural area was 87.9% Caucasian and 6.2%
      Hispanic, and the urban reported 67.3% Caucasian and 29% Hispanic. Both
      communities noted problems with care coordination, information about other
      available services, housing and transportation, and large underserved groups
      (persons with mild brain injury, non-English speakers, and persons without or
      with insufficient health insurance). The two communities noted strengths in
      having peer support networks and options for supported recreation. The rural
      community demonstrated strengths in dealing with trauma care but had few
      resources available for long-term rehabilitation and community-integrated
      services for its residents with brain injuries. The urban community uniquely had
      an array of alternative treatment approaches available.

PMID- 17558960
TI  - Disparities in Community Readiness for HIV/AIDS prevention.
AB  - HIV and AIDS as a community(1) issue have not been dealt with extensively in the
      literature. One model that offers promise for development of effective prevention
      and intervention efforts is the Community Readiness Model, a nine-stage model
      that assesses the level of readiness of a community to develop and implement
      prevention programming. Data are presented from a Community Readiness assessment
      of 30 rural U.S. communities: 10 African American, 10 Mexican American, and 10
      White non-Mexican American. Four to five key respondent interviews were conducted
      via telephone in each community using the Community Readiness Assessment protocol
      during 1999-2000. Limitations of the study and implications for prevention are
      discussed. This study was funded by the National Institute on Drug Abuse.

PMID- 17558961
TI  - American Indian women, HIV/AIDS, and health disparity.
AB  - Data are presented regarding the prevalence of HIV/AIDS among American Indian
      women. Health disparities found among American Indians are discussed and
      biological, economic, social, and behavioral risk factors associated with HIV are
      detailed. Recommendations are suggested to alleviate the spread of HIV among
      American Indian women and, in the process, to diminish a culture of treatment
      malpractice and a weakening of treatment ethics, racism, and genderism.

PMID- 17558962
TI  - Communicating (birth defects) prevention information to a hmong population in
      Wisconsin: a study of cultural relevance.
AB  - Compelling research from the early 1990s indicated a strong correlation between
      the consumption of the B-vitamin folic acid and the prevention of a serious birth
      defect (neural tube defect) in infants. This article examines numerous challenges
      the author faced when attempting to produce a culturally relevant folic acid
      brochure for Hmong women of childbearing age in LaCrosse, Wisconsin, part of a
      broad folic acid education program. An immediate challenge arose from the
      traditional Hmong belief that birth defects can be either a curse or a gift,
      "preassigned" in a former life and therefore not preventable. Other challenges
      that were addressed included language, acculturation and nutrition, literacy,
      attitudes toward Western health care practices, and attitudes toward taking
      medications, including a daily multivitamin. In order for public health
      communicators to reach increasingly diverse ethnic and cultural identities with
      important health messages, it is essential that project planning start from the
      target group's cultural context. It is hoped that the lessons learned through
      this project can be applied to other communications efforts with other cultural
      groups.

PMID- 17558964
TI  - Phylogeny of extant and fossil Juglandaceae inferred from the integration of
      molecular and morphological data sets.
AB  - It is widely acknowledged that integrating fossils into data sets of extant taxa
      is imperative for proper placement of fossils, resolution of relationships, and a
      better understanding of character evolution. The importance of this process has
      been further magnified because of the crucial role of fossils in dating
      divergence times. Outstanding issues remain, including appropriate methods to
      place fossils in phylogenetic trees, the importance of molecules versus
      morphology in these analyses, as well as the impact of potentially large amounts
      of missing data for fossil taxa. In this study we used the angiosperm clade
      Juglandaceae as a model for investigating methods of integrating fossils into a
      phylogenetic framework of extant taxa. The clade has a rich fossil record
      relative to low extant diversity, as well as a robust molecular phylogeny and
      morphological database for extant taxa. After combining fossil organ genera into
      composite and terminal taxa, our objectives were to (1) compare multiple methods
      for the integration of the fossils and extant taxa (including total evidence,
      molecular scaffolds, and molecular matrix representation with parsimony [MRP]);
      (2) explore the impact of missing data (incomplete taxa and characters) and the
      evidence for placing fossils on the topology; (3) simulate the phylogenetic
      effect of missing data by creating "artificial fossils"; and (4) place fossils
      and compare the impact of single and multiple fossil constraints in estimating
      the age of clades. Despite large and variable amounts of missing data, each of
      the methods provided reasonable placement of both fossils and simulated
      "artificial fossils" in the phylogeny previously inferred only from extant taxa.
      Our results clearly show that the amount of missing data in any given taxon is
      not by itself an operational guideline for excluding fossils from analysis. Three
      fossil taxa (Cruciptera simsonii, Paleoplatycarya wingii, and Platycarya
      americana) were placed within crown clades containing living taxa for which
      relationships previously had been suggested based on morphology, whereas
      Polyptera manningii, a mosaic taxon with equivocal affinities, was placed firmly
      as sister to two modern crown clades. The position of Paleooreomunnea stoneana
      was ambiguous with total evidence but conclusive with DNA scaffolds and MRP.
      There was less disturbance of relationships among extant taxa using a total
      evidence approach, and the DNA scaffold approach did not provide improved
      resolution or internal support for clades compared to total evidence, whereas
      weighted MRP retained comparable levels of support but lost crown clade
      resolution. Multiple internal minimum age constraints generally provided
      reasonable age estimates, but the use of single constraints provided by extinct
      genera tended to underestimate clade ages.

PMID- 17558965
TI  - Resource-aware taxon selection for maximizing phylogenetic diversity.
AB  - Phylogenetic diversity (PD) is a useful metric for selecting taxa in a range of
      biological applications, for example, bioconservation and genomics, where the
      selection is usually constrained by the limited availability of resources. We
      formalize taxon selection as a conceptually simple optimization problem, aiming
      to maximize PD subject to resource constraints. This allows us to take into
      account the different amounts of resources required by the different taxa.
      Although this is a computationally difficult problem, we present a dynamic
      programming algorithm that solves it in pseudo-polynomial time. Our algorithm can
      also solve many instances of the Noah's Ark Problem, a more realistic formulation
      of taxon selection for biodiversity conservation that allows for taxon-specific
      extinction risks. These instances extend the set of problems for which solutions
      are available beyond previously known greedy-tractable cases. Finally, we discuss
      the relevance of our results to real-life scenarios.

PMID- 17558966
TI  - Majority-rule supertrees.
AB  - Most supertree methods proposed to date are essentially ad hoc, rather than
      designed with particular properties in mind. Although the supertree problem
      remains difficult, one promising avenue is to develop from better understood
      consensus methods to the more general supertree setting. Here, we generalize the
      widely used majority-rule consensus method to the supertree setting. The majority
      rule consensus tree is the strict consensus of the median trees under the
      symmetric-difference metric, so we can generalize the consensus method by
      generalizing this metric to trees with differing leaf sets. There are two
      different natural generalizations, based on pruning or grafting leaves to produce
      comparable trees, and these two generalizations produce two different, but
      related, majority-rule supertree methods.

PMID- 17558967
TI  - Inferring speciation times under an episodic molecular clock.
AB  - We extend our recently developed Markov chain Monte Carlo algorithm for Bayesian
      estimation of species divergence times to allow variable evolutionary rates among
      lineages. The method can use heterogeneous data from multiple gene loci and
      accommodate multiple fossil calibrations. Uncertainties in fossil calibrations
      are described using flexible statistical distributions. The prior for divergence
      times for nodes lacking fossil calibrations is specified by use of a birth-death
      process with species sampling. The prior for lineage-specific substitution rates
      is specified using either a model with autocorrelated rates among adjacent
      lineages (based on a geometric Brownian motion model of rate drift) or a model
      with independent rates among lineages specified by a log-normal probability
      distribution. We develop an infinite-sites theory, which predicts that when the
      amount of sequence data approaches infinity, the width of the posterior
      credibility interval and the posterior mean of divergence times form a perfect
      linear relationship, with the slope indicating uncertainties in time estimates
      that cannot be reduced by sequence data alone. Simulations are used to study the
      influence of among-lineage rate variation and the number of loci sampled on the
      uncertainty of divergence time estimates. The analysis suggests that posterior
      time estimates typically involve considerable uncertainties even with an infinite
      amount of sequence data, and that the reliability and precision of fossil
      calibrations are critically important to divergence time estimation. We apply our
      new algorithms to two empirical data sets and compare the results with those
      obtained in previous Bayesian and likelihood analyses. The results demonstrate
      the utility of our new algorithms.

PMID- 17558968
TI  - Testosterone deficiency and the metabolic syndrome.
AB  - Evidence is presented to link components of the metabolic syndrome to
      testosterone deficiency and obesity. Testosterone deficiency in hypogonadism or
      testosterone deprivation in normo-gonadotropic men increases fat mass as well as
      fasting insulin levels. Testosterone supplementation (TS) in a dose dependent
      manner, increase lean body mass (LBM), reduces fat mass, body mass index (BMI)
      and waist hip ratio in both young and elderly hypogonadal men. A negative
      association between T and insulin resistance as well as impaired glucose
      intolerance has been demonstrated and in type 2 diabetic men TS improves
      metabolic parameters. TS improves most components of the metabolic syndrome and
      also reduces inflammatory cytokines.

PMID- 17558969
TI  - Adding to the controversy: pitfalls in the diagnosis of testosterone deficiency
      syndromes with questionnaires and biochemistry.
AB  - PURPOSE: To determine the value of available questionnaires used for the
      diagnosis of testosterone deficiency syndromes (TDS) by correlating their ratings
      with a panel of hormonal determinations in a male population. MATERIALS AND
      METHODS: Participants completed the ADAM questionnaire and underwent biochemical
      evaluation at the local site. Assessments determined entry into Group A
      (symptomatic) or Group B (non-symptomatic). After stratification, subjects
      provided a morning sample of blood, completed the Aging Male Survey (AMS) and the
      newly developed Canadian Society for the Study of the Aging Male (CSAM-Q)
      questionnaires. Serum aliquots were analysed at a central lab for 8 putative
      markers commonly associated with symptomatic testosterone deficiency associated
      with aging: total testosterone (T); bioavailable T (BT); dehydroepiandrosterone
      sulphate (DHEA-S); sex-hormone binding globulin (SHBG); luteinizing hormone (LH),
      prolactin (PRL); thyroid-stimulating hormone (TSH) and insulin-like growth factor
      1 (IGF-1). RESULTS: 92 men were screened; of these 59 (mean age of 58+/-11 years)
      completed the study, 30 (51%) scored positively (mean 61.5 years) to the ADAM
      while 29 (49%) did not (mean 54.1 years). For the AMS the weight of the three
      domains (psychological, somato-vegetative and sexual) was significantly greater
      in Group A (p<0.001) than in Group B. Equally, for the CAS questionnaire, the
      scores for the variables energy, global performance, frequency of intercourse,
      mood and quality of sleep were lower in Group A than in their asymptomatic
      counterparts (p<0.001). The domain of memory assessment within the CSSAM-Q was
      not discriminatory. ADAM and AMS are self-administered and completed within 10
      minutes. CSSAM-Q is more time consuming, requires an investigator to administer,
      and memory domain is biased in favour of specific professional training. No
      difference was found between the two groups in 6 of 8 biochemical tests. However,
      significant lower values (p<0.001) were found for DHEA-S and IGF-1 in the
      symptomatic group as compared with the non-symptomatic cohort. CONCLUSIONS: This
      study confirms that newer, more complex tools perform similarly to the simpler
      ADAM questionnaire. The lack of correlation between the clinical picture and the
      most commonly used biochemical confirmatory tests, again, clearly points to the
      paramount importance of the clinical evaluation. An emphasis and reliance on
      serum T alone hinders the clinician's ability to manage testosterone deficiency
      syndromes (TDS).

PMID- 17558970
TI  - The effect of physiotherapy training programme on postural stability in men with
      hip osteoarthritis.
AB  - This study presents the influence of a physiotherapy training programme over the
      standing balance in elderly hip osteoarthritis (OA) patients. The aim of this
      study was to analyse the standing balance in elderly male hip OA patients, and to
      investigate how the physiotherapy training programme could significantly improve
      the balance. The tests were performed on a group of selected OA patients as well
      as on a group of age- and sex-matched healthy control subjects before and after
      the physiotherapy training programme. The significant differences were observed
      between the results of tests performed before and after the physiotherapy
      training programme, and also between the hip OA patients and the control subjects
      in all CPF parameters, in both sagittal and frontal planes. In conclusion, the
      hip OA has an effect on the process of maintaining the standing balance. Moreover
      the physiotherapy training programme significantly improves the postural
      stability in male hip OA patients.

PMID- 17558971
TI  - The microanatomy of trabecular bone in young normal and osteoporotic elderly
      males.
AB  - Normally there is a gradual continual loss of cortical and trabecular bone in
      both men and women as they age. Osteopenia and osteoporosis are conditions in
      which the loss results in brittle bones that fracture easily. Males with low
      testosterone and hypogonadism are predisposed to osteoporosis and prevention
      tends to be overshadowed by the greater problem in postmenopausal women. The
      ability of the skeleton to resist external forces depends partly upon the amount
      of bone present and partly upon other factors including cancellous bone
      microarchitecture. This is examined in iliac crest bone biopsies from idiopathic
      osteoporotic men, mean age 60+/-12 SD years [n=16]. These were compared with a
      healthy control group (autopsy samples), mean age 30+/-8.9 years [n=28] with the
      aim of examining the pattern of cancellous atrophy in male idiopathic
      osteoporosis. Undecalcified specimens were embedded in methylmethacrylate and
      prepared for histomorphometry. Sections were analysed using an automated
      trabecular analysis system (TAS), whereby a binary image was created. Area
      measurements including the trabecular surface and distance measurements including
      the trabecular width were made. The binary image was thinned to its medial
      framework and the node and terminus number as indices of trabecular
      interconnection were recorded, together with the strut length. Results (median
      (range)) showed a lower percentage bone volume in the elderly osteoporotic male,
      10.2% (5.4-23.1) compared to young normals 25.2% (14.6-43.9), p<0.001. The
      trabeculae tended to be thinner, 95.7 microm (66.7-170.7) c.f. 120.8 microm (75.8
      208.6) and considerably fewer in number, 11.1 (2.1-31.4) c.f. 48.3 (25.4-66.9),
      p<0.001 per field and in particular the number of nodes, 2.1 (0.15-14) c.f. 40.6
      (10.3-74.1) per field and the node: terminus ratio fell to 0.13 (0.01-1.19) c.f.
      controls 0.98 (0.24-6.69), p<0.001. It was concluded that the pattern of
      cancellous atrophy in male idiopathic osteoporosis differs from normal aging and
      resembles that in postmenopausal women. Results using the automated TAS confirm
      previous observations made manually.

PMID- 17558975
TI  - Response to open peer commentaries on "A Kantian moral duty for the soon to be
      demented to commit suicide".

PMID- 17558976
TI  - Is it sound public policy to let the terminally ill access experimental medical
      innovations?

PMID- 17558977
TI  - Public health, public trust and lobbying.
AB  - Each year, infection with Human Papillomavirus (HPV) leads to millions of
      abnormal Pap smears and thousands of cases of cervical cancer in the US.
      Throughout the developing world, where Pap smears are less common, HPV is a
      leading cause of cancer death among women. So when the international
      pharmaceutical giant Merck developed a vaccine that could prevent infection with
      several key strains of HPV, the public health community was anxious to celebrate
      a major advance. But then marketing and lobbying got in the way. Merck chose to
      pursue an aggressive lobbying campaign, trying to make its new vaccine mandatory
      for young girls. The campaign stoked public mistrust about how vaccines come to
      be mandated, and now it's not just Merck's public image that has taken a hit. The
      public health community has also been affected. What is the lesson to be learned
      from this story? Public health communication relies on public trust.

PMID- 17558978
TI  - Conscientious objection and emergency contraception.
AB  - This article argues that practitioners have a professional ethical obligation to
      dispense emergency contraception, even given conscientious objection to this
      treatment. This recent controversy affects all medical professionals, including
      physicians as well as pharmacists. This article begins by analyzing the option of
      referring the patient to another willing provider. Objecting professionals may
      conscientiously refuse because they consider emergency contraception to be
      equivalent to abortion or because they believe contraception itself is immoral.
      This article critically evaluates these reasons and concludes that they do not
      successfully support conscientious objection in this context. Contrary to the
      views of other thinkers, it is not possible to easily strike a respectful balance
      between the interests of objecting providers and patients in this case. As
      medical professionals, providers have an ethical duty to inform women of this
      option and provide emergency contraception when this treatment is requested.

PMID- 17558979
TI  - Pharmacists and the social contract.

PMID- 17558980
TI  - The pharmacist's personal and professional integrity.

PMID- 17558981
TI  - The necessity of conscience and the unspoken ends of medicine.

PMID- 17558982
TI  - Conscientious objection? Yes, but make sure it is genuine.

PMID- 17558983
TI  - Reasons and healthcare professionals' claims of conscience.

PMID- 17558984
TI  - Should professional associations sanction conscientious refusals?

PMID- 17558985
TI  - When to grant conscientious objector status.

PMID- 17558986
TI  - Gatekeeping and personal values: misuses of professional roles.

PMID- 17558987
TI  - Conscientious objection: does the zero-probability argument work?

PMID- 17558988
TI  - Caution: conscience is the limb on which medical ethics sits.

PMID- 17558989
TI  - Conscientious objection the morning after.

PMID- 17558990
TI  - Moral disagreement and providing emergency contraception: a pluralistic
      alternative.

PMID- 17558991
TI  - A Kantian moral duty for the soon-to-be demented to commit suicide.
AB  - It has been argued that, on Kantian grounds, pedophiles, rapists and murderers
      are morally obligated to take their own lives prior to committing a violent
      action that will end their moral agency. That is, to avoid destroying the agent's
      moral life by performing a morally suicidal action, the agent, while he still is
      a moral agent, should end his body's life. Although the cases of dementia and the
      morally reprehensible are vastly different, this Kantian interpretation might be
      useful in the debate on the permissibility of suicide for those facing dementia's
      effects. If moral agents have a duty to act as moral agents, then those who will
      lose their moral identity as moral agents have an obligation to themselves to end
      their physical lives prior to losing their dignity as persons.

PMID- 17558992
TI  - A Kantian duty to commit suicide and its implications for bioethics.

PMID- 17558993
TI  - Can suicide be a rational and ethical act in persons with early or pre-dementia?

PMID- 17558994
TI  - Kant condemned all suicide.

PMID- 17558995
TI  - Suicide fails to pass the categorical imperative.

PMID- 17558996
TI  - A modest proposal for reducing imperfection and resolving world hunger.

PMID- 17558997
TI  - Person-al journeys: reflections on personhood and dementia based on ethnographic
      research and family experience.

PMID- 17558998
TI  - Dementia as a moral harm.

PMID- 17558999
TI  - Lucinda among the bioethicists.

PMID- 17559000
TI  - Is there life not worthy of living?

PMID- 17559001
TI  - Morality of suicide in dementia.

PMID- 17559005
TI  - An appraisal of the role of the European Society of Contraception in the
      promotion of reproductive health.

PMID- 17559006
TI  - Combined hormonal contraception and venous thromboembolism.
AB  - This review provides an update of knowledge regarding venous thromboembolism
      (VTE) and combined hormonal contraceptives (CHCs) in the light of new progestins
      and new administration routes for CHCs. Practical recommendations are also
      offered. The association between the use of combined oral contraceptives (COCs)
      and an increased risk of VTE has been known about for many years, it being
      related mainly to the dose of oestrogen; however, recent research has also shown
      the influence of the type of progestin. When compared to COCs containing
      levonorgestrel or norethisterone, those containing desogestrel or gestodene
      present a two-fold greater risk of VTE; for COCs containing cyproterone acetate,
      the risk is four-fold greater, while there are no or insufficient data for those
      containing norgestimate, chlormadinone acetate or drospirenone. With regard to
      the contraceptive patch, the available data suggest that the risk of VTE is
      similar to that observed with COCs. There are no data concerning vaginal rings.
      The greatest risk of COC-associated VTE occurs during the first year of use, thus
      suggesting the existence of a predisposing condition, such as being a carrier of
      a thrombogenic mutation with which the COCs would exert a synergistic effect.
      Routine screening for such conditions is not justified. Changes in haemostatic
      variables produced by COCs, for example, acquired resistance to protein C, could
      be linked to VTE, although it has yet to be demonstrated that such alterations
      are related to a clinical risk of VTE among COC users. At present there are no
      laboratory tests able to detect an increased risk of VTE in asymptomatic women.
      The key procedures in terms of ensuring the safe use of this contraceptive method
      are a full clinical, personal and family history, in order to evaluate risk
      factors for VTE and cardiovascular disease, along with the recording of blood
      pressure and body mass index prior to the prescription of COCs.

PMID- 17559007
TI  - Impact of piroxicam beta-cyclodextrin on the efficacy of the intrauterine device
      in a rat model.
AB  - OBJECTIVE: To elucidate the effect of piroxicam beta-cyclodextrin (PbetaCD), a
      non-steroidal anti-inflammatory drug (NSAID), on the efficacy of the intrauterine
      device (IUD) in a rat model. METHODS: Forty nulliparous female Wistar rats were
      allocated to one of four groups, comprising each 10 of these animals. Group I:
      neither IUD nor medication; group II: IUD, but no medication; group III: IUD and
      PbetaCD; and group IV: PbetaCD only. In groups II and III, a string of 3/0 silk
      suture of 2 cm long was transcervically placed in one of the horns of the
      bicornuate uterus of the rat. Rats in group III were treated during the 18 days
      following IUD placement with 3 mg/kg/day PbetaCD administered via a feeding tube;
      group IV received PbetaCD for the same length of time, but had no IUD inserted.
      The rats were then mated. Thereafter, vaginal smears were taken and assessed
      daily, in the early morning, for the presence of spermatozoa. The day when
      spermatozoa were detected was considered to be the first day of gestation. On
      gestational day 19, both uterine horns of all rats were evaluated for the
      presence and number of embryos. RESULTS: In group II, mean embryo counts in the
      horn with or without IUD were 1.0 +/- 0.2 and 4.5 +/- 0.3, respectively (p <
      0.01). The comparison of group II with group I showed that the presence of an IUD
      in one horn did not affect the mean embryo counts in the contralateral horn (4.5
      +/- 0.3 versus 5.1 +/- 0.9, p > 0.05). In groups II and III, mean numbers of
      embryos in the horn with IUD were 1.0 +/- 0.2 and 2.7 +/- 0.4, respectively (p <
      0.01). No difference in the mean embryo counts was observed between group I (5.1
      +/- 0.9) and IV (4.8 +/- 0.9; p > 0.05). CONCLUSIONS: The IUD had a contraceptive
      effect in the rat model. The IUD in one horn did not affect the number of embryos
      in the contralateral horn. In this model, IUDs appear to exert a local effect,
      i.e. counteracted by PbetaCD. This drug had no adverse effect on the fertility of
      rats without IUD in situ.

PMID- 17559008
TI  - Preventing pregnancy: a girls' issue. Seventeen-year-old Swedish boys'
      perceptions on abortion, reproduction and use of contraception.
AB  - OBJECTIVE: To gain deeper understanding of how teenage males view abortion,
      adolescent fatherhood, sexual behavior, and use of contraception. METHOD: We
      conducted six focus-group interviews with 17-year-old boys (n = 40). The
      interviews were tape-recorded, transcribed verbatim, and analyzed using manifest
      content analysis. RESULTS: Adolescent fatherhood was considered to be a
      catastrophe and abortion a moral dilemma. Most participants agreed that the
      unrestricted right to decide on abortion rests upon the girl, but some were
      frustrated by not having any legal right to influence the decision. Contraceptive
      failure was viewed as common and mainly due to the influence of alcohol or in
      relation to unplanned sex. Boys perceived girls as having a greater
      responsibility in avoiding pregnancy, and they often put a blind trust in the
      girls' use of hormonal contraceptives or initiation of emergency contraception.
      Several groups had insufficient knowledge about fetal development and other
      aspects of reproduction. Many were unsatisfied with the sex education they had
      received at school, but still considered it to be an important counterweight to
      other sources of information concerning sex, such as pornography. CONCLUSION:
      Equal responsibility among boys and girls regarding reproductive issues is still
      a challenge, but nevertheless an important key to the prevention of unwanted
      pregnancies.

PMID- 17559009
TI  - Contraceptive use and associated factors among Swedish high school students.
AB  - OBJECTIVES: To investigate self-reported sexual experiences, abortions, sexually
      transmitted infections (STIs), use of contraception and possible influencing
      factors on contraceptive use among Swedish high school students. METHODS: An
      anonymous classroom survey was distributed to a random sample (n = 924) of 18
      year-old high school students in a medium-sized Swedish city. The response rate
      was 78% (n = 718). RESULTS: Three out of four students had experienced
      intercourse and the majority of them stated that they were satisfied with their
      sexual life. Few students reported having had an abortion (5%) or a STI (4%).
      Alcohol use appeared the most important contributing risk factor for non-use of
      contraception in relation to both first and latest intercourse, and the young men
      reported more unprotected latest intercourse than the young women did.
      CONCLUSION: The fact that young men appear less inclined to use contraception is
      disturbing, and must be addressed in sexual education and individual counseling
      to promote a better sexual health for adolescents.

PMID- 17559010
TI  - Sexual behaviour and contraception in people under the age of 20 in Alicante,
      Spain.
AB  - OBJECTIVE: To describe and to analyse the relationship between patterns of
      sexually-risky behaviour and emergency contraception among young females
      attending a Family Planning Centre (FPC). METHODS: Data was obtained from a
      systematic analysis of 384 health records. RESULTS: Mean age of the sample
      subjects was 18.24 years (SD 1.47, range 13-20). Of these, 92% were single, 60%
      students and 83% were with the same partner. Age at first intercourse was 16.5
      years (SD 1.52, range 11-20). Those who used condoms systematically totalled 72%.
      Mean number of sexual partners was 1.85 (SD 2.91, range 1-50). A total of 9% had
      become pregnant and 2% had had an abortion. Emergency contraception was resorted
      to by 26% of the young women on at least one occasion. Emergency contraception
      was related to younger age at first sexual intercourse (p < 0.001) and to a great
      number of partners (p = 0.011). Of the total number of subjects, 48.4%
      demonstrated sexually-risky behaviour. This behaviour was related to alcohol
      consumption (p < 0.0001) and to the existence of dysfunction (p < 0.001).
      CONCLUSIONS: Spanish youngsters have enough knowledge regarding contraception.
      Condoms are mostly used on the occasion of a first sexual intercourse. However,
      the frequency of sexually-risky behaviour is still high due to the limited use of
      condoms in successive sexual relations with the same partner. Sexually-risky
      behaviour is also related to a high number of partners and to alcohol consumption
      on weekends.

PMID- 17559011
TI  - College students in Nigeria underestimate their risk of contracting HIV/AIDS
      infection.
AB  - OBJECTIVES: To assess the perceptions of personal risk of acquiring HIV/AIDS
      infection among students of selected tertiary institutions in Osun State, Nigeria
      and to determine the correlates of perceptions of personal risk of infection.
      METHODS: The study employed a cross-sectional descriptive design. An interviewer
      administered questionnaire was applied to the 405 study participants and
      correlates of perceptions of personal risk of HIV infection were evaluated using
      multiple logistic regression analysis, confidence intervals and odd ratios.
      RESULTS: Only 15% of the students perceived themselves to be at moderate-to-high
      risk of acquiring HIV infection compared with 85% who perceived themselves to be
      at little or no risk. Investigators' assessment of risk status of the
      participants revealed that 77% of the participants were actually at high risk of
      infection and only 23% at low risk. The sensitivity, specificity and negative
      predictive value of the students' self-perception of personal risk compared with
      their assessed risk were 7, 58 and 16%, respectively, with a Kappa statistic of
      0.178. The only significant correlate of self-perception of personal risk was a
      recent symptom of sexually transmitted infections. CONCLUSIONS: College students
      exhibited an 'optimism bias' associating high rates of HIV risk indicators with
      low levels of perceived personal risk of infection. This has implications for
      HIV/AIDS control in Nigeria.

PMID- 17559012
TI  - Parent-adolescent sex communication in China.
AB  - BACKGROUND: Communication concerning sexual matters between parents and their
      adolescent children serve as a protective factor and exerts a favourable
      influence on adolescents' sexual behaviours. As limited data regarding parent
      adolescent sex communication are available in China, this study was undertaken
      with the aim of exploring the patterns and related factors of such communication
      and its relationship with adolescent sexual behaviour. STUDY DESIGN: Community
      based data were collected in 2001 in Changchun, China. Unmarried adolescents 15
      19 years of age (322 young men and 360 young women) were included in a survey
      using self-administered questionnaires. RESULTS: Overall, sex communication with
      parents was relatively infrequent. There was a significant gender difference in
      the pattern of sex communication, with male adolescents being more likely to talk
      with fathers and female adolescents with mothers. Logistic regression analysis
      revealed that gender of adolescents, quality of communication with mothers on
      general topics, and adolescent's perception of mother being the main source of
      sex knowledge were predictive of the level of sex communication between mother
      and her adolescent children. CONCLUSION: This study reveals that communication
      regarding sexual matters between parents and adolescents was limited in China.
      The quality of communication on general topics between parents and their
      adolescent children is one of the important factors related to sex communication
      between them. It is essential that Chinese parents are better informed and
      skilled to be involved, in addition to school and community, in the sex education
      of their adolescent children. They should be able to communicate appropriately on
      sex-related issues with them.

PMID- 17559013
TI  - Factors associated with contraceptive use in Tehran, Iran.
AB  - OBJECTIVES: In spite of the government's efforts, the prevalence of contraceptive
      use in Iran is only 55.4%. Health concerns, side effects, failure of the methods
      and some demographic issues, among which education, age, and number of daughters,
      have a great influence on the enforcement of contraceptive measures. The aim of
      the present study was to identify factors affecting contraceptive use in Iran.
      METHODS: Data from the project 'The study of contraceptive practice in Tehran,
      1999-2000' were analyzed with regard to the factors associated with contraceptive
      use by Iranian couples. A total of 4042 women at reproductive ages who had
      delivered in one of the 12 teaching hospitals of Tehran and had at least one
      child that lived for at least 24 hours after birth, were interviewed using a
      questionnaire that gathered information about their socio-demographic status,
      fertility history, and other characteristics. RESULTS: Using a multinomial
      logistic regression, it was found that the woman's age, her own or her husband's
      level of education, previous awareness about contraceptive methods, number of
      abortions, and number of sons and daughters were factors that were significantly
      associated with contraceptive use. CONCLUSIONS: A number of factors affect the
      application of contraceptive measures. It is essential that health policy makers
      be aware of these to promote contraception and population control.

PMID- 17559014
TI  - Do perceived health risks outweigh the benefits of modern contraceptives? A
      qualitative study in a suburban population in Istanbul, Turkey.
AB  - OBJECTIVES: To evaluate the health concerns and the perceived non-contraceptive
      benefits of modern contraceptive methods through utilizing qualitative methods.
      METHODS: Six focus group discussions were carried out with a total of 53 married
      women in a socio-economically disadvantaged community in Istanbul, Turkey.
      RESULTS: Women had a vague knowledge of the mechanism of menstruation. Some women
      believed that the uterus was filled with blood -- termed 'dirty blood' -- which
      should be eliminated during menstruation in order to stay healthy. For this
      reason, amenorrhoea was recognized as the important disadvantage of the progestin
      only injectable contraceptives. While the participants mentioned fallacious and
      exaggerated side effects related to modern methods they did not recognize their
      non-contraceptive benefits. Most women gained the information concerning side
      effects through their social networks. Sometimes the information acquired was
      based on rumours that biased women against the modern contraceptives.
      CONCLUSIONS: Women outweighed the risks, some of which were fallacious and
      exaggerated, against the benefits of modern contraceptives. It is crucial to
      address health concerns of women and what they 'heard' from their peers during
      counselling sessions. Also the non-contraceptive health benefits of modern
      methods should be well emphasized. Since informal sources are prevalent, the
      effectiveness of peer education should be studied in this community.

PMID- 17559015
TI  - Emergency contraception in Cuba with 10 mg of mifepristone.
AB  - BACKGROUND: Mifepristone in a dose of 10 mg is an effective emergency
      contraceptive when administered up to 120 hours after unprotected coitus.
      METHODS: Between May 2003 and February 2005, we conducted in Cuba a single-arm
      trial to evaluate the effectiveness of 10 mg mifepristone for emergency
      contraception up to 6 days after unprotected coitus. A total of 635 women who
      requested emergency contraception after a single act of unprotected intercourse
      were included in the study. RESULTS: After treatment there were 7/635 (1.1%)
      pregnancies (95% CI 0.4-2.3%). Pregnancy that might have occurred was prevented
      in 88.0% of the cases (95% CI 77.1-95.1%). The most common side effects reported
      by participants were fatigue (10.7%), dizziness (6.1%) and nausea (4.9%);
      vomiting was only reported by 0.6%. In 38/635 (6.0%) women menstruation was
      delayed more than 7 days. CONCLUSIONS: Mifepristone 10 mg administered is an
      effective emergency contraceptive with an acceptable profile of side effects up
      to five days, but greater studies are necessary to verify its efficacy up to 6
      days after unprotected intercourse.

PMID- 17559016
TI  - Man's involvement in the experience of abortion and the dynamics of the couple's
      relationship: a clinical study.
AB  - OBJECTIVES: To investigate the way men experience abortion from a psychodynamic
      perspective in order to understand better the impact of this experience on their
      own image as men and on the couple's relationship. METHODS: In-depth semi
      structured interviews with 16 men in Belgium and 14 men in Greece. RESULTS:
      Intrapsychic factors seem to play for men an important role in their experience
      of abortion, whatever their cultural context and contraceptive practices. Two
      thirds of the men who agreed to participate in the research disagreed with their
      partner's decision to have an abortion. Such men may feel that it is impossible
      for them to fulfill themselves, in particular as potential fathers. This
      impossibility is, according to men, linked to women's attitudes, but may also be
      related to their own difficult identification with parental images and to socio
      professional concerns. CONCLUSIONS: Abortion can create tensions and/or conflicts
      between partners by revealing their contradictory desires. It is suggested that
      institutions where men and women are heard can help both partners to outlive this
      experience as a constructive step in their personal psychosocial evolution and in
      their relationship.

PMID- 17559017
TI  - Supply and demand challenges to modern contraceptive use in Azerbaijan.
AB  - OBJECTIVES: We conducted a survey of health facilities and household members to
      determine supply and demand aspects of contraceptive use in Azerbaijan. METHODS:
      In June 2005, we conducted interviews with 758 women and 253 men in a community
      based survey in 40 communities in five districts. We also surveyed a sample of
      health facilities and pharmacies and conducted interviews with key informants.
      RESULTS: Both men and women in these communities desire small families, yet
      significant supply and demand impediments exist. Despite community interest, lack
      of knowledge of contraception is prevalent. Fear of side effects plays a role in
      non-use and discontinuation of modern methods, although little opportunity exists
      for counselling on side effects, since few health workers are trained. An
      obstacle to use is legislation that only allows contraception to be prescribed by
      gynaecologists, who are mostly concentrated in the hospitals of urban centres.
      However, the main handicap to increased use of modern contraception, is
      insufficient contraceptive supply. Not only is there a lack of method choice
      nationally, but few of the facilities we surveyed had any contraceptives
      available. This situation threatens to worsen as the United Nations Population
      Fund (UNFPA) retracts commodities' funding. CONCLUSIONS: The lack of knowledge of
      modern contraception, lack of trained staff and poor commodity availability
      signals that much remains to be done for the people of Azerbaijan to achieve
      their fertility control goals.

PMID- 17559018
TI  - Ectopic pregnancy following emergency contraception with ethinyloestradiol
      levonorgestrel: a case report.
AB  - BACKGROUND: Emergency contraception with ethinyloestradiol-levonorgestrel is
      effective, and ectopic pregnancy following its failure is rare. CASE: A 21-year
      old nulligravid Japanese woman with regular menstrual periods took
      ethinyloestradiol-levonorgestrel pills for emergency contraception (EC) 36 and 48
      hours after a coitus complicated by retention of the condom in the vagina. She
      started bleeding vaginally 24 days after that intercourse. As the bleeding
      continued for three weeks she consulted a gynaecologist. The pregnancy test was
      positive. Two weeks later she complained of lower abdominal pain, and
      transvaginal ultrasonography suggested a pelvic blood collection. At emergency
      surgery, she was found to have a left tubal pregnancy. CONCLUSION: Although
      ectopic pregnancy after failure of EC is rare, one should be alert to its
      possible occurrence.

PMID- 17559019
TI  - Uterine perforation by intrauterine devices and systems.

PMID- 17559021
TI  - [Traumatologic risk in ambulatory cardiac rehabilitation groups to leisure time
      sports groups of healthy athletes].
AB  - INTRODUCTION: Rehabilitation in ambulatory heart groups has become well
      established in comprehensive cardiac care. The prevention of injuries is critical
      to the safety and efficiency of the program. METHODS: Questionnaires were mailed
      to the ambulatory heart groups in the state of Hessen, Germany and answered by
      1935/13 000 (15 %) patients (65.9 +/- 7.6 years, 1504/1935 (77.7 %) men covering
      approximately 674,000 patient exercise hours. RESULTS: Seventy-eight of the 106
      (73.6 %) injuries reported occurred during games encompassing 28/106 (26.4 %)
      strains, 24/106 (22.6 %) bruises, 17/106 (16.0 %) sprains, 11/106 (10.4 %) bone
      fractures, 6/106 (5.7 %) ruptured tendons, 8/106 (7.5 %) ruptured muscles, 3/106
      (2.8 %) ruptured ligaments, and 9/106 (8.5 %) miscellaneous. The injury risk was
      neither related to the cardiovascular diagnosis, the prevalence of diabetes, body
      mass index, previous sport experience, duration of participation in
      rehabilitation programs, nor to the participant's age. Patients on anticoagulants
      or after cardiovascular surgery had no excess risk. Gender was the only
      independent predictor of injuries. In men the overall incidence of injuries was
      higher (97/1504 [6.4 %]) than in women (9/431 [2.1 %]), p < 0.0005) while the
      severity was higher in women (6/9 = 66.7 % vs. 22/97 = 22.7 % p < 0.001). The
      injuries were treated by elastic bandages or band-aids in 69/106 (65.1 %), by
      splinting in 4/106 (3.8 %), by local injections in 4/106 (3.8 %), by massages in
      3/106 (2.8 %), and by others in 26/106 (24.5 %). Five of the 106 (4.7 %) injuries
      required hospitalization. CONCLUSION: The traumatologic risk in the
      rehabilitation of cardiovascular outpatients is associated with a low incidence
      of injuries.

PMID- 17559022
TI  - [Primary repair of extensor tendon injuries of the hand].
AB  - Knowledge of the functional anatomy of the extensor tendons with the sliding
      mechanism is essential for better understanding the surgical therapy and the
      postoperative care in the different trauma zones of the extensor tendon. In
      addition the localization of the injury is very important for the clinical
      findings, therapy, after-care and long term prognosis. Anatomical facts, injury
      mechanisms and associated injuries have to be considered in the therapy concept.
      Several therapy possibilities are known: immobilizing with splint for the closed
      rupture in zone I, reinsertion in zone III (with a temporary Kirschner-wire
      pinning), tendon suture, tendon transplantation or transposition. Controlled
      mobilization after suture should be aspired (similar to the one of the flexor
      tendon) especially after squeezing, multi tendon injuries, tendon
      transplantations or injuries in zone VII. Pathological and iatrogenic tendon
      lesions are special forms of tendon injuries.

PMID- 17559023
TI  - [Bone tunnel fixation versus suture anchor: mid- and long-term results after
      distal biceps tendon rupture].
AB  - AIM: The aim of this study was to assess the range of movement, isometric and
      isokinetic postoperative outcome, Morrey score and heterotropic ossifications
      after refixation of distal biceps tendon rupture with either suture anchor or
      bone tunnel fixation. METHODS: 48 patients were surgically treated between 1990
      and 2005. Elbow function was investigated isometrically and isokinetically with
      the CYBEX-NORM. The presence and extent of heterotropic ossifications were
      assessed by A/P and lateral view X-rays. The Morrey score was used to evaluate
      the clinical outcome. RESULTS: 13 patients received distal biceps refixation with
      the bone tunnel method and 35 with suture anchors. The range of motion of the
      elbow was statistically not significantly different except for pronation, which
      was slightly but significantly reduced after bone tunnel refixation. Isometric
      and isokinetic results as well as Morrey scores were statistically not different
      between the two surgical techniques. Both groups showed excellent postoperative
      results. CONCLUSION: Bone tunnel and suture anchor techniques are both equal and
      sufficient methods for the refixation of distal biceps tendon ruptures with
      excellent clinical and functional postoperative results. The slight but
      significantly reduced pronation after bone tunnel refixation was clinically not
      relevant.

PMID- 17559024
TI  - [Open augmented repair according to Silfverskjold for Achilles tendon rupture: an
      alternative for athletes?].
AB  - AIM: The most recent meta-analysis of randomized trials recommended open repair
      for competitive athletes suffering from Achilles tendon rupture due to low re
      rupture rates and recommended for all other patients percutaneous repair. The
      report did not include patients with open augmented repair. The aim of this study
      was to analyse our results with open augmented repair after Silfverskjold and to
      discuss whether this method is an alternative form of treatment, especially for
      athletes. METHODS: This retrospective study included all patients who received
      open augmented repair in the Silfverskjold technique between the years 1996 and
      2002. A total of 104 patients were clinically evaluated, involving ultrasound as
      well, and were scored according to the Thermann scale. The average age was 43
      years. The operation took place on average within 5.7 days. Twenty athletes were
      identified and were compared with non-athletes using the Thermann scale and the
      two randomsample t-tests. The follow-up period averaged 3.7 years. RESULTS:
      Overall, the results were rated as good, with an average of 88.1 points. The re
      rupture rate was 1.9% (2 out of 104) with a deep infection incidence of 2.8% (3
      out of 104). Athletes averaged 88.7 and non-athletes 88.0 points. No significant
      difference was recorded (t=0.98). Nineteen out of 20 (95%) athletes and 48 out of
      84 (57%) non-athletes were able to return to their original level of sport
      activity. CONCLUSIONS: Open augmented repair after Silfverskjold is found to be a
      real alternative to simple open reconstruction of Achilles tendon ruptures.
      Clinical outcome in both athletes and nonathletes was recorded as good to very
      good. Especially athletes were able to regain their original activity level with
      an overall low re-rupture and infection rate.

PMID- 17559025
TI  - A novel polyacetylene significantly inhibits angiogenesis and promotes apoptosis
      in human endothelial cells through activation of the CDK inhibitors and caspase
      7.
AB  - A novel bioactive polyacetylene compound, 1,2-dihydroxy-5(E)-tridecene-7,9,11
      triyne (compound 1), was identified from the Bidens pilosa extract using an ex
      vivo primary human umbilical vein endothelium cell (HUVEC) bioassay-guided
      fractionation protocol. Our results demonstrate that compound 1 (at 2.5
      microg/mL) possessed significant anti-angiogenic effects, as manifested by an
      inhibition of HUVEC proliferation, migration, and the formation of tube-like
      structures in collagen gel. Moreover, compound 1 induced HUVECs to undergo cell
      death in a concentration- and time-dependent manner. The mechanisms underlying
      these pharmacological effects include reduced expression of cell cycle mediators
      such as CDK4, cyclins D1 and A, retinoblastoma (Rb) and vascular endothelial
      growth factor receptor 1 (VEGFR-1), and promotion of caspase-mediated activation
      of CDK inhibitors p21(Cip1) and p27(Kip). Moreover, apoptotic induction in HUVECs
      mediated by compound 1 was found to be in part through overexpression of FasL
      protein, down-regulation of anti-apoptotic Bcl-2, and activation of caspase-7 and
      poly(ADP-ribose) polymerase. This study demonstrates the potent anti-angiogenic
      and apoptotic activities of compound 1, suggesting that phytocompounds such as
      polyacetylenes deserve more attention regarding their potential as candidates for
      anti-angiogenic therapeutics.

PMID- 17559026
TI  - Enuresis persisting into adulthood.
AB  - INTRODUCTION: Nocturnal enuresis is a very common finding in children to the
      extent that many families and caregivers, alike, may dismiss it as a
      developmental stage rather than a disease. Persistence of nocturnal enuresis into
      adulthood, however, has received little discussion and is surrounded by
      fallacies. MATERIALS AND METHODS: All existing literature cited in PubMed between
      1970 and 2005 were reviewed using the search entries "nocturnal enuresis AND
      adult*". RESULT: Of the 220 papers reviewed, enuresis persisting into adulthood
      was covered in only 87. Those aspects pertinent to this subset of patients were
      placed in focus. CONCLUSION: In contrast to the numerous researches on childhood
      enuresis, persistent adulthood enuresis is an under discussed subject, distinct
      in a few aspects of its etiology and management described herein.

PMID- 17559027
TI  - Extracorporeal shock wave lithotripsy in prone and supine positions for patients
      with upper ureteral calculi.
AB  - INTRODUCTION: The aim of this study was to evaluate the treatment of upper
      ureteral calculi with extracorporeal shock wave lithotripsy (SWL) in the supine
      and prone positions. MATERIALS AND METHODS: A total of 68 patients with upper
      ureteral calculi underwent SWL. In 35 patients, the procedure was performed in
      the supine position (group 1), while in the 33 remainders, it was performed in
      the prone position (group 2). The stone-free rate, the number of SWL sessions
      required, and the number of shocks per treatment session were compared between
      the 2 groups. RESULTS: The mean calculus size was 12.4 +/- 3.1 mm and 12.2 +/-
      2.9 mm in groups 1 and 2, respectively. The stone-free rate was 81.8% in group 1
      and 82.9% in group 2 (P = .91). The number of sessions for achieving the stone
      free status was similar in the patients of the 2 groups (1.9 +/- 0.8 in group 1
      versus 1.9 +/- 0.8 in group 2; P = .79). The mean number of shock waves per
      treatment session was not significantly different between the 2 groups. No major
      complications were seen and none of the patients required hospitalization,
      placement of a ureteral catheter, or a double-J stent. CONCLUSION: Our study
      showed that in the prone position, treatment of the upper ureteral calculi by SWL
      is as safe and effective as the supine position.

PMID- 17559028
TI  - Pediatric cystine calculi in west of Iran: a study of 22 cases.
AB  - INTRODUCTION: Cystinuria is an autosomal recessive disorder which clinically
      presents as cystine calculi. In this study, we reviewed cystine calculi cases in
      the west of Iran to determine their common presentations and response to
      different therapeutic modalities. MATERIALS AND METHODS: Between 1999 and 2005,
      we had 22 pediatric patients (11 boys and 11 girls) with cystine calculi. The
      demographic characteristics and clinical data of the patients as well as the
      treatment results were reviewed. RESULTS: The mean age of the patients was 34.20
      +/- 42.99 months (range, 4 to 156 months). They were followed for a mean duration
      of 23 months (range, 3 to 70 months). Thirteen patients (59.1%) had bilateral and
      9 (41%) had unilateral kidney calculi. The sizes of the calculi were between 2 mm
      and 20 mm. Nine patients (41%) had renal atrophic changes and 1 (4.5%) had
      obstructive acute renal failure. Hydration and urinary alkalinization were
      administrated to all of the patients which yielded an excellent result in 54.5%
      and a poor response in 27.2%. Captopril started for 5 patients was effective only
      in 1. D-penicillamine had no favorable response. Extracorporeal shockwave
      lithotripsy was successful in 5 attempts and failed in 4. Surgical interventions
      were performed for 13 patients (59.1%) and 6 (27.2%) required more than 1
      surgical operation. CONCLUSION: We recommend metabolic workup of childhood
      urolithiasis and appropriate medical management of its underlying disease. We
      also recommend minimally invasive urologic techniques including shockwave
      lithotripsy only when there are clear indications for nonmedical procedures.

PMID- 17559029
TI  - Technetium Tc 99m dimercaptosuccinic acid renal scintigraphy in diagnosis of
      urinary tract infections in children with negative culture.
AB  - INTRODUCTION: The aim of this study was to evaluate the accuracy of Technetium Tc
      99m dimercaptosuccinic acid (99mTc-DMSA) renal scintigraphy in the diagnosis of
      urinary tract infection (UTI) in children with suspected infection but with a
      negative urine culture. MATERIALS AND METHODS: The records of all children with
      suspected or definite diagnosis of UTI presented during a 2-year period were
      reviewed in this study. Abnormal findings on renal scintigraphy, voiding
      cystourethrography (VCUG), and ultrasonography were evaluated and compared
      between the patients with the definite diagnosis of UTI and those with suspected
      UTI and negative urine cultures. RESULTS: Of 210 patients, 86 had a definite
      diagnosis of UTI (group 1) and 124 had suspected UTI without a positive culture
      (group 2). Abnormal findings on DMSA scans were seen in 76 patients (88.4%) in
      group 1 and 84 (67.7%) in group 2. Vesicoureteral reflux was detected by VCUG in
      50% and 32.3% of the patients in groups 1 and 2, respectively. In group 2,
      vesicoureteral reflux was seen in 40.5% of the patients with abnormal DMSA scan.
      Ultrasonography findings were abnormal in 51.3% and 39.8% of the patients with
      abnormal DMSA scan findings in groups 1 and 2, respectively. CONCLUSION:
      According to our findings, in children with a negative urine culture and abnormal
      urinalysis, 99mTc-DMSA renal scintigraphy is helpful in diagnosing UTI and
      vesicoureteral reflux; we recommend VCUG when DMSA scan supports UTI despite a
      negative urine culture and a normal ultrasonography.

PMID- 17559030
TI  - Prediction of prostatic involvement by transitional cell carcinoma of the bladder
      using pathologic characteristics of the bladder tumor.
AB  - INTRODUCTION: The aim of this prospective study is to determine the relationship
      between the pathologic characteristics of the transitional cell carcinoma (TCC)
      of the bladder and prostatic involvement. MATERIALS AND METHODS: Sixty men with
      bladder TCC underwent standard radical cystoprostatectomy and were enrolled in
      this study. Vascular and perineural invasion, maximum diameter of the tumor,
      presence of carcinoma in situ, distance between the tumor and the bladder neck,
      and grade and local stage of the tumor were recorded and their relation with
      prostatic involvement was studied. In addition, hydronephrosis and age of the
      patients were included in the analysis. RESULTS: The mean age of the patients was
      63.9 +/- 11.1 years. Of 60 men included in this study, 15 patients were found to
      have prostatic involvement with TCC (25%). Univariate statistical analyses showed
      that vascular invasion and the distance between the tumor and the bladder neck
      were significantly related to the prostatic involvement (P = .007; P < .001).
      But, in the logistic regression, only the distance between the tumor and the
      bladder neck was significantly related to the prostatic involvement (P = .001).
      CONCLUSION: This study suggests that the probability of prostatic involvement in
      patients with bladder TCC tumors near the bladder neck is high. Prostate-sparing
      or capsule-sparing cystectomy should be avoided in such patients.

PMID- 17559031
TI  - Diagnosis of bladder cancer by urine survivin, an inhibitor of apoptosis: a
      preliminary report.
AB  - INTRODUCTION: Survivin is an inhibitor of apoptosis that is expressed in
      undifferentiated tissues like tumors. Detection of survivin in urine has been
      proposed as a diagnostic marker for bladder cancer. We evaluated the urine
      samples of patients with bladder cancer for survivin and compared them with
      healthy controls. MATERIALS AND METHODS: The urine specimens of 20 patients with
      transitional cell carcinoma (TCC) of the bladder (group 1) and 18 controls
      without cancer (group 2) were collected before cystoscopy and assessed for
      survivin by reverse transcriptase polymerase chain reaction. RESULTS: All
      patients except 1 in group 1 were men. Urine specimens were positive for survivin
      in 18 (90%) and 9 (50%) patients of groups 1 and 2, respectively (P = .007).
      Sixteen patients with TCC had urine cytology, of which 6 (37.5%) were positive.
      Urine survivin was positive in all 10 patients with negative cytology. Nine
      patients in this group had low-grade tumors. CONCLUSION: Urine survivin seems to
      have a higher sensitivity than urine cytology, especially in low-grade bladder
      cancer. The quantitative measurement of survivin in urine by advanced techniques
      may provide a better diagnostic and prognostic tool. However, the clinical use of
      survivin and its association with different stages and grades of TCC still
      requires more studies.

PMID- 17559032
TI  - Sperm nuclear DNA in ejaculates of fertile and infertile men: correlation with
      semen parameters.
AB  - INTRODUCTION: Our aim was to compare the nuclear DNA integrity of the spermatozoa
      from infertile men with abnormal semen parameters with that from normospermic
      fertile men, and to evaluate the relationship between the sperm DNA integrity and
      semen parameters. MATERIALS AND METHODS: Thirty ejaculate samples with abnormal
      semen analysis and 30 ejaculates with normal semen parameters were randomly
      collected from infertile and fertile men, respectively. The acridine orange test
      was used to assess the integrity of sperm DNA. RESULTS: The number of ejaculates
      with a DNA Fragmentation Index (DFI) above 30% were 16 (53.3%) and 22 (73.3%) in
      fertile and infertile subjects, respectively (P = .10). The mean DFI was 37.7 +/-
      19.6% and 46.1 +/- 16.7% in the fertile and infertile subjects, respectively (P =
      .24). The DFI of the fertile men with normal sperm morphology (12 patients)
      ranged from 1% to 80%. In the samples with oligoasthenospermia, mean DFI was 52.7
      +/- 17.9%. There were 2 samples with severe teratospermia (normal morphology less
      than 4%) and DFIs of 70% and 87%. There were no significant correlations between
      the DNA integrity and the 3 parameters of semen quality in our 60 subjects.
      CONCLUSION: Our results failed to show any significant difference in the DNA
      integrity of the spermatozoa between infertile and fertile men. Also, no
      correlation was noticed between the DNA abnormality and the semen parameters in
      the studied samples.

PMID- 17559033
TI  - Urethroplasty for long anterior urethral strictures: report of long-term results.
AB  - INTRODUCTION: We reviewed the long-term outcome of substitution urethroplasty
      with skin flaps for anterior urethral strictures, comparing 1-stage with 2-stage
      repairs. MATERIALS AND METHODS: A total of 45 patients with urethral strictures,
      2.5 cm or longer, had undergone skin flap urethroplasty. A 1-stage surgical
      operation had been done in 10 patients (Orandi and bilateral pedicle island of
      penile skin) and a 2-stage surgical repair had been performed in 35 using the
      Johanson technique. They were followed up by retrograde urethrography for 1 to 10
      years. RESULTS: The mean age of the patients was 46.3 +/- 17.1 years. Etiology of
      the stricture was instrumentation in 33.3% of the patients, urethritis in 28.9%,
      trauma in 13.3%, and unknown in 24.5%. At the first postoperative year, the
      success rate was 75.6%. This rate was 71.4% and 90% for the 1-stage and 2-stage
      operations, respectively (P = .23). There were 1 (10%) and 10 (28.6%) cases of
      recurrent structure and 1 (10%) and 3 (8.6%) cases of fistula in the patients
      with the 1-stage and 2-stage operations within the first year, respectively.
      During the 5 postoperative years, 70% of the patients with the 1-stage repair,
      57.1% with the 2-stage repair, and 60% in total had no complications. CONCLUSION:
      Based on the previous studies and our experience, we recommend skin flap
      urethroplasty. However, some measures such as proper tailoring of the flap and
      the extension of the incision onto the intact segments should be considered for
      achieving a better outcome.

PMID- 17559034
TI  - Fournier gangrene: a series of 12 patients.
AB  - INTRODUCTION: Fournier gangrene is a rare, rapidly progressive, necrotizing
      fasciitis of the external genitalia, the perineum, or the abdominal wall that is
      associated with high morbidity and mortality. In this series, we describe 12
      patients with Fournier gangrene who had presented to our medical center.
      MATERIALS AND METHODS: Twelve men had been diagnosed with Fournier gangrene in
      Shohada-e-Tajrish hospital between March 2002 and September 2005. Their medical
      records were reviewed and the Fournier Gangrene Severity Index scores before and
      after the treatment were determined. RESULTS: Fifty percent of the patients were
      diabetic and their mean age was 58.2 +/- 17.8 years. The mean delay between the
      onset of the disease and the admission was 4.9 days and the mortality rate was
      16.6%. The median Fournier Gangrene Severity Index scores before the admission
      and at the time of discharge were 4.5 (range, 0 to 11) and 0 (range, 0 to 9),
      respectively (P = .005). One of the patients who died had the scores of 11 and 9,
      respectively. Split-thickness skin graft was performed for 5 patients (41.7%).
      CONCLUSION: In Fournier gangrene, a rapid diagnosis and emergent surgical
      intervention is crucial. The Fournier Gangrene Severity Index seems to be an
      excellent tool for outcome prediction.

PMID- 17559035
TI  - Epidemiology of urogenital trauma in Iran: results of the Iranian National Trauma
      Project.
AB  - INTRODUCTION: We report the incidence, distribution, etiology, and outcome of the
      urogenital trauma in 8 major cities of Iran according to the database of national
      trauma project. MATERIALS AND METHODS: Between 2000 and 2004, we prospectively
      collected the data of all the traumatic patients hospitalized for more than 24
      hours in 8 cities (Tehran, Mashad, Ahwaz, Shiraz, Tabriz, Qom, Kermanshah, and
      Babol). We analysed the data taken from 17,753 trauma admissions. Patients with
      sustained urogenital traumas were identified and studied. RESULTS: A total of 175
      patients (0.98%) had injuries to the urogenital system. Male to female ratio was
      4. The patients' mean age was 25 +/- 16 years (range, 2 to 80 years). Of 175
      patients, 159 (90.9%) had blunt trauma and 16 (9.1%) had penetrating trauma. Road
      traffic accident was the most common cause of trauma (65.1%). The most common
      injured organs were the kidney in 61.1% and the bladder in 13.7%. One hundred and
      forty-two patients (81.1%) had associated intra-abdominal injuries and 129
      (73.7%) had other accompanying injuries. Sixty (34.2%) patients required surgical
      intervention. Nine patients (5.2%) died due to the severity of the injuries. All
      patients who died had severe injuries (Injury Severity Score >12). CONCLUSION: In
      Iran, blunt traumas including road traffic accidents are the main cause of
      urogenital traumas. The majority of the patients with urogenital trauma have
      multiple injuries and require a multidisciplinary approach.

PMID- 17559036
TI  - Retrocaval ureter: a study of 13 cases.
AB  - INTRODUCTION: The aim of this study was to report our 23-year experience in the
      diagnosis and treatment of retrocaval ureter. MATERIALS AND METHODS: Data from 13
      patients with retrocaval ureter were reviewed. Intravenous urography and
      retrograde pyelography had been used for confirming the diagnosis. All of the
      patients had been symptomatic and undergone surgery. A control intravenous
      urography had been performed 6 months postoperatively. RESULTS: The mean age of
      the patients was 23 years (range, 12 to 37 years). Twelve patients (92.3%) were
      men. The clinical manifestations were pyelonephritis in 7 (53.8%), right flank
      pain in 4 (30.8%), gross hematuria in 1 (7.7%), and ureteral calculus in 1
      (7.7%). All of the patients had type 1 right-sided retrocaval ureter. Associated
      anomalies were seen in none of the patients. The control intravenous urography
      showed improvement of renal function. CONCLUSION: In our patients, the most
      common cause of referral was pyelonephritis. In symptomatic cases, operation is
      needed and can improve renal function.

PMID- 17559037
TI  - Polyorchidism: a case report and review of literature.

PMID- 17559038
TI  - Urethral tumors: a report of 6 cases.

PMID- 17559039
TI  - Duplicate publication: justifiable in a different language?

PMID- 17559040
TI  - Genetics of azoospermia: current knowledge, clinical implications, and future
      directions. Part I.
AB  - INTRODUCTION: We reviewed the most recent advances in the genetics of male
      infertility focusing on karyotypic abnormalities, obstructive azoospermia, and
      idiopathic hypogonadotropic hypogonadism. MATERIALS AND METHODS: To update our
      previous review, we searched the literature using PubMed and skimmed articles
      published from January 1998 to November 2006. There were 52, 30, and 41 relevant
      articles to our subject on karyotypic abnormalities, obstructive azoospermia, and
      idiopathic hypogonadotropic hypogonadism, respectively. The full texts of these
      articles and their bibliographic information were reviewed and a total of 93 were
      used to contribute to this review. RESULTS: The frequency of sperm aneulpoidy in
      karyotypic abnormalities such as 47,XXY and 47,XYY is higher than that in the
      healthy individuals, but transmission of the abnormalities to the offspring is
      rare and the outcomes of assisted reproductive techniques are encouraging.
      Mutations in the cystic fibrosis gene are detectable in up to 80% of men with
      congenital bilateral absence of the vas deferens. However, there is a
      considerable diversity among different populations and the role of other
      potential causes is not ruled out yet. Autosomal and X-linked genetic aberrations
      in men with idiopathic hypogonadotropic hypogonadism are now well known. As
      hormone replacement therapy can provide the chance of fathering children in these
      patients, the risk of mutations' transmission, especially the autosomal dominant
      ones, is high. CONCLUSION: In the recent decade, a parallel progress has been
      made in the understanding of the genetics of men with azoospermia and the
      treatment modalities for these patients. Assisted reproductive techniques can
      help most of the patients, but there are several genetic abnormalities that must
      be considered before decision making for treatment of their infertility.

PMID- 17559041
TI  - Diagnostic application of flexible cystoscope in pelvic fracture urethral
      distraction defects.
AB  - INTRODUCTION: The aim of this study was to evaluate the diagnostic value of
      antegrade flexible cystoscopy in pelvic fracture urethral distraction defects
      (PFUDD). MATERIALS AND METHODS: Between 1999 and 2004, a total of 111 patients
      with PFUDD were evaluated by antegrade flexible cystoscopy. The flexible
      cystoscope was introduced into the posterior urethra and the area was evaluated
      for any probable fistula, false passages, or displacement of the posterior
      urethra. For preventing misalignment, flexible cystoscope was also used during
      the urethroplasty to open the posterior urethra at its exact distal point.
      RESULTS: Posterior urethra ended distal to the external sphincter in 16 patients
      (14.4%). Five (4.5%) and 9 (8.1%) patients had severe displacement of the
      posterior end of the urethra and bladder neck false passage, respectively.
      Prostatic urethrorectal fistula was detected in 1 patient. Another 1 patient had
      bladder rhabdomyoma. CONCLUSION: Flexible cystoscopy is a valuable procedure in
      the evaluation of the bladder, the bladder neck, and the posterior urethra in
      patients with urethral distraction defects and complements voiding cystography
      before the surgery. It is also helpful for showing the exact distal point of the
      proximal urethra during urethroplasty in cases with displaced posterior urethra.

PMID- 17559042
TI  - Distilled water as an irrigation fluid in percutaneous nephrolithotomy.
AB  - INTRODUCTION: The aim of this study was to evaluate the effect of distilled water
      as an irrigation fluid for percutaneous nephrolithotomy (PCNL) on the serum
      concentrations of sodium. MATERIALS AND METHODS: A total of 30 patients with
      kidney calculi underwent tubeless PCNL using distilled water as the irrigation
      fluid. During the procedure, intravenous Ringer lactate solution was used if
      necessary. The patients received infusion of two-thirds dextrose 5% and one-third
      normal saline solution postoperatively. Four blood samples were taken to
      determine serum sodium and potassium levels at admission, just before the
      operation, after the operation, and on the first postoperative day. RESULTS: The
      mean distilled water used was 8.1 L (range, 5.6 L to 11.2 L). Target and complete
      stone-free rates were 100% and 80%, respectively. None of the patients developed
      hyponatremia. The mean serum levels of sodium (meq/L) were 141.5 (range, 140 to
      143), 140.7 (range, 125 to 159), 139.7 (range, 125 to 164), and 138.9 (range, 125
      to 146), respectively (P = .005). Comparing every 2 samples, a significant
      difference was seen only between samples 1 and 4 (P = .005). Serum levels of
      potassium were all in normal range and there was no difference between the 4
      samples (P = .12). CONCLUSION: Our findings showed that using distilled water as
      an irrigation fluid during PCNL does not result in a clinically significant
      decrease in the serum level of sodium and can be used if necessary. However,
      evaluation of the serum sodium level on the postoperative day is mandatory.

PMID- 17559043
TI  - Extensive surgical management for renal tumors with inferior vena cava thrombus.
AB  - INTRODUCTION: The aim of this study was to evaluate the outcome in patients with
      renal cell carcinoma (RCC) and the inferior vena cava (IVC) or the right atrium
      tumor thrombus that were treated with radical nephrectomy and thrombectomy.
      MATERIALS AND METHODS: Eleven of a total of 105 patients who underwent radical
      nephrectomy due to RCC had tumor thrombus extended to the IVC and/or the right
      atrium. We evaluated the surgical techniques used and the perioperative mortality
      and morbidity in these patients. RESULTS: The median age of the patients was 47
      years (range, 16 to 59 years). They all underwent radical nephrectomy with
      cavotomy, tumor thrombus removal, and lymphadenectomy. Eight patients underwent
      extracorporeal circulation and hypothermic circulatory arrest; 2, temporary
      venovenous bypass by chevron incision and median sternotomy; and 1, only chevron
      incision with mobilization of the right lobe of the liver and cross-clamping
      proximal to the tumor thrombus and cavotomy. In 1 case, a solitary liver
      metastasis was excised and the patient died within 30 days postoperatively
      because of massive hemorrhage due to liver metastatectomy. Two patients had
      invasion to the IVC wall and 7 had pathological lymph node involvement. Four
      patients were tumor free (follow-up range, 9 to 18 months) and 7 died due to
      multiple metastases during the follow-up. CONCLUSION: This study supports the
      role of extensive surgical treatment as the best initial management of patients
      with renal cancer extended to the IVC only in highly selected cases.

PMID- 17559044
TI  - p53 protein in serum and urine samples of patients with bladder transitional cell
      carcinoma and its overexpression in tumoral tissue.
AB  - INTRODUCTION: The aim of this study was to evaluate the levels of p53 protein in
      serum and urine samples of patients with bladder transitional cell carcinoma
      (TCC) and their relation with the overexpression of p53 in the tumoral tissue.
      MATERIALS AND METHODS: A total of 39 patients with bladder TCC were evaluated for
      p53 protein in their serum and urine samples and the overexpression of this
      marker in their tumoral tissue. RESULTS: Of 39 patients with bladder TCC, 29
      (74.4%) had tissue specimens positive for p53 protein overexpression, 20 (51.3%)
      had p53 protein in their serum samples, and 27 (69.2%) had this protein in their
      urine samples. A positive immunohistochemical finding was more common in higher
      grades of the bladder tumor (P = .03), but not in higher stages (P = .07).
      Eighteen of 20 patients (90%) with a positive serum for p53 showed protein
      overexpression in the tumoral tissue of the bladder (P = .03). Of 27 patients
      with a positive urine sample, 25 (92.6%) had p53 overexpression in their bladder
      tissue, and of the remainder 12 patients with a negative p53 protein in their
      urine samples, 8 (66.7%) had no evidence of p53 protein overexpression in their
      tumoral tissue (P < .001). The grade and stage of tumor had no correlation with
      serum or urinary p53. CONCLUSION: According to our findings, a positive serum or
      urine sample for p53 protein is highly associated with the overexpression of p53
      protein in the tumoral tissue of patients with bladder TCC.

PMID- 17559045
TI  - Immediate intravesical instillation of mitomycin C after transurethral resection
      of bladder tumor in patients with low-risk superficial transitional cell
      carcinoma of bladder.
AB  - INTRODUCTION: The aim of this study was to evaluate the effect of immediate
      intravesical instillation of mitomycin C after transurethral resection of bladder
      tumor (TURBT) in patients with low-risk superficial transitional cell carcinoma
      (TCC). MATERIALS AND METHODS: A total of 43 patients with low-risk superficial
      bladder cancer were randomly assigned into two groups after the surgery; 22
      patients in group 1 were treated by immediate instillation of mitomycin C after
      TURBT, and 21 patients in group 2 received placebo. The two groups were compared
      using urine cytology and cystoscopy during the 24 postoperative months. RESULTS:
      Recurrence within the first 3 months was reported in none of the patients in
      group 1 and 5 in group 2 (P = .02). Of these, 4 had recurrence of tumor in the
      primary site. At 12 and 24 months, there were 1 patient (4.5%) in group 1 and 8
      (38.1%) in group 2 with recurrence (P = .007). We had no patients with multifocal
      recurrence in group 1, but 3 (14.2%) in group 2. Nine-month tumor-free survival
      rate was 95% in group 1. Three-, 6-, 9-, and 12-month tumor-free survival rates
      in group 2 were 76%, 71%, 66%, and 62%, respectively (P = .007). None of the
      patients in group 1 and 3 in group 2 (14.3%) experienced some degrees of tumor
      progression (P = .06). CONCLUSION: Immediate instillation of mitomycin C after
      TURBT seems to be effective in the recurrence reduction and increase of
      recurrence-free interval at least in short term.

PMID- 17559046
TI  - Changes in plasma concentrations of hypoxanthine and xanthine in renal vein as an
      index of delayed kidney allograft function.
AB  - INTRODUCTION: The aim of this study was to evaluate the plasma levels of
      hypoxanthine (HX) and xanthine in the renal vein blood samples for prediction of
      delayed graft function (DGF). MATERIALS AND METHODS: Two blood samples were taken
      from 47 kidney recipients, intraoperatively. The first sample was obtained from a
      peripheral vein before vascular anastomosis and the second from the allograft
      renal vein, 15 minutes after the anastomosis. Purine metabolites including
      xanthine and HX were measured and their associations with operative time,
      anastomosis time, frequency of clamping, urine output, and DGF were evaluated.
      RESULTS: The mean levels of xanthine and HX were 0.12 +/- 0.10 mg/L and 0.37 +/-
      0.17 mg/L in the first plasma samples, respectively. Thirty patients (63%) had no
      significant changes in neither of their purine metabolite levels and 17 (37%) had
      higher levels of HX, but not xanthine, in their second samples. Only anastomosis
      time had a significant relation with the level of the metabolites (P = .04).
      Three patients (10%) with no changes in the metabolites and 5 (29.4%) with higher
      HX levels had DGF (P = .12). The anastomosis time and frequency of vascular
      clamping were higher and the urine output after the anastomosis was lower in the
      patients with DGF. CONCLUSION: Cold ischemia in kidney transplantation causes a
      mild increase in the HX concentration indicative of short-term ischemia effects
      on the cell metabolism. But it cannot predict DGF. Anastomosis time, frequency of
      clamping, and urine output after the anastomosis are more sensitive indices.

PMID- 17559047
TI  - Skin diseases in kidney transplant recipients.
AB  - INTRODUCTION: The aim of this study was to evaluate the frequency of skin
      diseases in kidney transplant recipients. MATERIALS AND METHODS: This cross
      sectional study was performed on 233 kidney transplant recipients in Ekbatan
      Hospital of Hamedan in 2004. The patients were examined by a dermatologist and
      diagnosis was made on the basis of clinical observations. Biopsies and scraping
      of the lesions were taken whenever necessary. RESULTS: Of the patients, 226 (97%)
      suffered from one or more skin lesions. The most common lesions were drug
      related, including hypertrichosis, gingival hyperplasia, acne, and cushingoid
      feature which were detected in 86.7% of the patients. Also, infectious and
      premalignant or malignant lesions (actinic keratosis, squamous cell carcinoma,
      and basal cell carcinoma) were seen in 48.9% and 14.2% of the patients. The mean
      duration of immunosuppressive therapy was significantly higher in patients with
      infectious skin diseases (P < .001). CONCLUSION: Skin lesions are a significant
      problem in kidney transplant recipients. A careful monitoring of these patients
      is recommended in order to detect these lesions in early stages and treat them.

PMID- 17559048
TI  - Public attitudes toward cadaveric organ donation: a survey in Ahwaz.
AB  - INTRODUCTION: The aim of this study was to evaluate the attitudes of the
      residents of Ahwaz toward organ donation after brain death. MATERIALS AND
      METHODS: A total of 1000 people between 15 and 70 years of age were selected by
      cluster sampling in Ahwaz, south-west of Iran. A questionnaire was designed about
      the attitudes of the interviewees toward organ donation after brain death by
      themselves and by their family members, demanding compensation for organ
      donation, and the need for consent or testimony. RESULTS: Of the participants,
      75% were pro organ donation, while 22% were against it and the remaining 3% had
      no specific idea. Age, sex, and occupation did not influence the attitudes;
      however, the ethnicity, educational level, economic status, and having a loved
      one in need of organ transplantation significantly increased the willingness of
      these people for organ donation (P < .05). Regarding the issue of demanding
      compensation for organ donation, 27% of the participants were in favor of the
      idea and 73% disagreed. A higher proportion of the participants with higher
      educational levels believed in organ donation without any consent or testimony (P
      = .02). CONCLUSION: According to our study, many people are pro organ donation
      after death. It is necessary to have a regular program for these people to give
      them the opportunity to register and receive a donation card. For the people who
      do not have the tendency for the matter, we had better try to increase their
      knowledge by educational programs and provide sufficient information.

PMID- 17559049
TI  - Improvement of erectile dysfunction after kidney transplantation: the role of the
      associated factors.
AB  - INTRODUCTION: The aim of this study was to evaluate erectile dysfunction (ED) in
      hemodialysis patients and the factors influencing ED after a successful kidney
      transplantation. MATERIALS AND METHODS: A total of 64 patients on hemodialysis
      were evaluated before and 6 months after the kidney transplantation. They were
      all recipients of their first kidney allografts from living unrelated donors and
      had a functional kidney allograft during the follow-up. The 5-item version of the
      International Index of Erectile Function (IIEF-5) was used to assess their
      erectile function. A group of age-matched controls were compared with them before
      transplantation. The effects of pretransplant IIEF-5 score, age at
      transplantation, the artery used for anastomosis, and duration of the dialysis
      prior to transplantation on ED were also studied. RESULTS: Fifty-six of the
      patients (87.5%) and 23 of the controls (35.9%) had ED (P < .001). The prevalence
      of ED was 87.5% in the hemodialysis patients. There was no relationship between
      the duration of dialysis and the severity of ED. Successful transplantation
      improved IIEF-5 score significantly (13.6 5.2 before and 19.2 5.0 after
      transplantation; P < .001). Based on the IIEF-5 scores, the severity of ED
      increased in 6 (9.4%) patients; 8 (12.5%) experienced no change in their erectile
      function; and 50 (78.1%) reported an improved erectile function. Preoperative
      IIEF-5 score and age at transplantation had statistically significant
      associations with ED improvement (P < .001; P = .02). CONCLUSION: Erectile
      dysfunction is highly prevalent in hemodialysis patients and significantly
      improves after successful kidney transplantation. Younger patients with a less
      severe ED have the most improvement after transplantation.

PMID- 17559050
TI  - Angiography and segmental artery embolization in renal stab wound.

PMID- 17559051
TI  - A giant congenital posterior urethral diverticulum associated with renal
      dysplasia.

PMID- 17559053
TI  - Notice of inadvertent duplicate publication.

PMID- 17559052
TI  - The role of surgery for local recurrence of renal Ewing's sarcoma: a case report.

PMID- 17559054
TI  - Bayesian sample size determination in non-sequential clinical trials: Statistical
      aspects and some regulatory considerations.
AB  - The most common Bayesian methods for sample size determination (SSD) are reviewed
      in the non-sequential context of a confirmatory phase III trial in drug
      development. After recalling the regulatory viewpoint on SSD, we discuss the
      relevance of the various priors applied to the planning of clinical trials. We
      then investigate whether these Bayesian methods could compete with the usual
      frequentist approach to SSD and be considered as acceptable from a regulatory
      viewpoint.

PMID- 17559055
TI  - The fetal portal vein: normal blood flow development during the second half of
      human pregnancy.
AB  - OBJECTIVES: The umbilical vein is the major source of blood for the fetal liver,
      but portal blood, which has not been measured directly in human fetuses, probably
      constitutes a physiologically important contribution. We aimed to establish a
      method for measuring blood flow in the fetal portal vein and to produce
      longitudinal reference ranges for diameter, blood flow velocities and volume
      blood flow during the second half of pregnancy. METHODS: After a pilot project to
      develop the measuring technique, 160 low-risk pregnant women were recruited to a
      longitudinal study that included ultrasound examinations at 4-5-week intervals
      starting at 20-22 weeks of gestation. The inner diameter (D) of the vessel was
      measured with a perpendicular insonation angle, and the time-averaged maximum
      blood velocity (TAMXV) and weighted mean velocity (VWMEAN) were recorded with an
      insonation directed along the long axis of the vessel. Portal flow was calculated
      as: Q = pi(D/2)(2) x h x TAMXV (where h is a velocity profile parameter and
      equals 0.5). Portal flow was normalized for estimated fetal weight based on birth
      weight percentiles. RESULTS: The portal vein could be visualized and measured in
      558/593 (94%) cases. Blood flow was pulsatile. D and TAMXV doubled during the
      second half of pregnancy (21-39 weeks), from 1.5 to 3.4 mm and from 8.4 to 14.9
      cm/s, respectively. Correspondingly, the portal flow increased from 5 to 41
      mL/min, and from 10 to 13 mL/min/kg when normalized for fetal weight. Similar
      results were achieved for VWMEAN. CONCLUSION: Portal flow can be measured with a
      standardized technique. It increases during the second half of pregnancy, even
      when normalized for fetal weight, suggesting that it has increasing importance in
      the fetal liver circulation.

PMID- 17559056
TI  - Accessory scrotum: prenatal sonographic features.

PMID- 17559057
TI  - Symmetry operation measures.
AB  - We introduce a new mathematical tool for quantifying the symmetry contents of
      molecular structures: the Symmetry Operation Measures. In this approach, we
      measure the minimal distance between a given structure and the structure which is
      obtained after applying a selected symmetry operation on it. If the given
      operation is a true symmetry operation for the structure, this distance is zero;
      otherwise it gives an indication of how different the transformed structure is
      from the original one. Specifically, we provide analytical solutions for measures
      of all the improper rotations, S n p, including mirror symmetry and inversion, as
      well as for all pure rotations, C n p. These measures provide information
      complementary to the Continuous Symmetry Measures (CSM) that evaluate the
      distance between a given structure and the nearest structure which belongs to a
      selected symmetry point-group.

PMID- 17559058
TI  - Design and synthesis of cationic Aib-containing antimicrobial peptides:
      conformational and biological studies.
AB  - Development of antimicrobial peptides has attracted considerable attention in
      recent years due to the excessive use of antibiotics, which has led to
      multiresistant bacteria. Cationic amphiphilic Aib-containing peptide models Ac
      (Aib-Arg-Aib-Leu)(n)-NH2, n = 1-4, and sequential cationic polypeptides (Arg-X
      Gly)(n), X = Ala, Val, Leu, were prepared and studied for their antimicrobial and
      hemolytic activity, as well as for their proteolytic stability. Ac-(Aib-Arg-Aib
      Leu)(n)-NH2, n = 2, 3 and the polypeptide (Arg-Leu-Gly)(n) exhibited significant
      antimicrobial activity, and they were nontoxic at their MIC values and resistant,
      in particular the Aib-peptide models, to enzymatic degradation. The
      conformational characteristics of the peptide models were studied by circular
      dichroism (CD). Structure-activity relationship studies revealed the importance
      of the amphipathic alpha-helical conformation of the reported peptides in
      inducing antimicrobial effects. It is concluded that peptide models comprising
      cationic amino acids (Arg), helicogenic and noncoding residues (Aib) and/or
      hydrophobic and helix-promoting components (Leu) may lead to the development of
      antimicrobial therapeutics.

PMID- 17559059
TI  - Total solid-phase synthesis of bombesin analogs with different functional groups
      at the C-terminus.
AB  - Five bombesin analogs with different functional groups at the C-terminus were
      synthesized using a solid-phase strategy. The protocols were optimized using 4
      (hydroxymethyl)benzoic acid (HMBA) resin to synthesize a common precursor
      followed by nucleophilic cleavage of the base sensitive peptide ester linkage.
      The C-terminal modifications included ethylamide, butylamide, methyl ester,
      propyl ester and hydrazide. Cleavage from the resin was possible with the fully
      protected or deprotected precursor peptide; however, higher purity of the final
      products was achieved when cleavage protocols were conducted after side-chain
      deprotection. The synthesized peptides were analyzed and characterized using
      reverse phase HPLC and ESI-MS. The peptides were obtained in 13-32% overall
      recovery, calculated from the coupling efficiency of the first amino acid
      residue, and in 91-97% purity.

PMID- 17559060
TI  - Exercise-induced modulation of calcineurin activity parallels the time course of
      myofibre transitions.
AB  - This study establishes a causal link between the limitation of myofibre
      transitions and modulation of calcineurin activity, during different exercise
      paradigms. We have designed a new swimming-based training protocol in order to
      draw a comparison between a high frequency and amplitude exercise (swimming) and
      low frequency and amplitude exercise (running). We initially analysed the time
      course of muscle adaptations to a 6- or 12-week swimming- or running-based
      training exercise program, on two muscles of the mouse calf, the slow-twitch
      soleus and the fast-twitch plantaris. The magnitude of exercise-induced muscle
      plasticity proved to be dependent on both the muscle type and the exercise
      paradigm. In contrast to the running-based training which generated a continuous
      increase of the slow phenotype throughout a 12-week training program, swimming
      induced transitions to a slower phenotype which ended after 6 weeks of training.
      We then compared the time course of the exercise-induced changes in calcineurin
      activity during muscle adaptation to training. Both exercises induced an initial
      activation followed by the inhibition of calcineurin. In the muscles of animals
      submitted to a 12-week swimming-based training, this inhibition was concomitant
      with the end of myofibre transition. Calcineurin inhibition was a consequence of
      the inhibition of its catalytic subunit gene expression on one hand, and of the
      expression increase of the modulatory calcineurin interacting proteins 1 gene
      (MCIP1), on the other. The present study provides the first experimental cues for
      an interpretation of muscle phenotypic variation control.

PMID- 17559061
TI  - Radiofrequency radiation (900 MHz) induces Egr-1 gene expression and affects cell
      cycle control in human neuroblastoma cells.
AB  - Many environmental signals, including ionizing radiation and UV rays, induce
      activation of Egr-1 gene, thus affecting cell growth and apoptosis. The paucity
      and the controversial knowledge about the effect of electromagnetic fields (EMF)
      exposure of nerve cells prompted us to investigate the bioeffects of
      radiofrequency (RF) radiation on SH-SY5Y neuroblastoma cells. The effect of a
      modulated RF field of 900 MHz, generated by a wire patch cell (WPC) antenna
      exposure system on Egr-1 gene expression, was studied as a function of time.
      Short-term exposures induced a transient increase in Egr-1 mRNA level paralleled
      with activation of the MAPK subtypes ERK1/2 and SAPK/JNK. The effects of RF
      radiations on cell growth rate and apoptosis were also studied. Exposure to RF
      radiation had an anti-proliferative activity in SH-SY5Y cells with a significant
      effect observed at 24 h. RF radiation impaired cell cycle progression, reaching a
      significant G2-M arrest. In addition, the appearance of the sub-G1 peak, a
      hallmark of apoptosis, was highlighted after a 24-h exposure, together with a
      significant decrease in mRNA levels of Bcl-2 and survivin genes, both interfering
      with signaling between G2-M arrest and apoptosis. Our results provide evidence
      that exposure to a 900 MHz-modulated RF radiation affect both Egr-1 gene
      expression and cell regulatory functions, involving apoptosis inhibitors like Bcl
      2 and survivin, thus providing important insights into a potentially broad
      mechanism for controlling in vitro cell viability.

PMID- 17559062
TI  - The most widespread desmosomal cadherin, desmoglein 2, is a novel target of
      caspase 3-mediated apoptotic machinery.
AB  - Apoptotic cells are known to regulate the ordered dismantling of intercellular
      contacts through caspase activity. Despite the important role of desmoglein (Dsg)
      2 in epithelial cell-cell adhesion, the fate of this widespread desmosomal
      cadherin during apoptosis is yet poorly understood. Here, by means of
      pharmacological approaches, we investigated whether Dsg2 was targeted by caspases
      in HaCaT and HT-29 cell lines undergoing staurosporine (STS)-induced apoptosis.
      Results showed that STS induced a caspase-dependent form of cell-death in both
      keratinocytes (HaCaT) and enterocytes (HT-29), that associated with progressive
      depletion of Dsg2 from cell lysates. The proteolytic processing of full-length
      Dsg2 resulted in the appearance of a 70-kDa fragment which was released into the
      cytosol. Consistently, immunofluorescence studies revealed that Dsg2 staining was
      abolished from cell surface whereas the cytoplasmic region of Dsg2 did localize
      intracellularly. Plakoglobin (Pg) also underwent cleavage and detached from Dsg2.
      Apoptotic changes paralleled with progressive loss of intercellular adhesion
      strength. All these biochemical, morphological, and functional changes were
      regulated by caspase 3. Indeed, in the presence of the caspase 3-inhibitor z-DEVD
      fmk, full-length Dsg2 protein levels were preserved, whereas the amount of the 70
      kDa fragment was maintained on control levels. Furthermore, cells pretreated with
      z-DEVD-fmk retained the membrane labeling of Dsg2. Taken together, our data
      demonstrate that the apoptotic processing of Dsg2 is mediated by caspase 3 in
      epithelial cells.

PMID- 17559063
TI  - Purified mouse egg zona pellucida glycoproteins polymerize into homomeric fibrils
      under non-denaturing conditions.
AB  - The mouse egg's zona pellucida (ZP) is composed of three glycoproteins, called
      ZP1, ZP2, and ZP3, that migrate as relatively broad, single bands on SDS-PAGE.
      The glycoproteins are organized within the ZP as a network of long interconnected
      fibrils that exhibit a structural periodicity. Here, ZP2 and ZP3 were purified by
      HPLC to homogeneity and analyzed by Blue Native- (BN-) PAGE and transmission
      electron microscopy (TEM), as well as by SDS-PAGE. As opposed to SDS-PAGE, BN
      PAGE, and TEM permit analysis of ZP2 and ZP3 under non-denaturing conditions. ZP2
      and ZP3 migrate on BN-PAGE, not as single bands, but as several discrete
      oligomers that give rise to larger structures which remain at the origin of the
      gel. Consistent with this, ZP2 and ZP3 are visualized by TEM as long
      interconnected fibrils that consist of contiguous beads. Therefore, under non
      denaturing conditions both purified ZP2 and ZP3 polymerize into higher order
      structures. These findings are of interest since purified ZP3 inhibits binding of
      mouse sperm to eggs and induces sperm to undergo the acrosome reaction in vitro.
      Results presented here suggest that these biological effects of ZP3 are due to
      binding of homomeric fibrils of ZP3 to sperm.

PMID- 17559064
TI  - Small potent ligands to the insulin-regulated aminopeptidase (IRAP)/AT(4)
      receptor.
AB  - Angiotensin IV analogs encompassing aromatic scaffolds replacing parts of the
      backbone of angiotensin IV have been synthesized and evaluated in biological
      assays. Several of the ligands displayed high affinities to the insulin-regulated
      aminopeptidase (IRAP)/AT(4) receptor. Displacement of the C-terminal of
      angiotensin IV with an o-substituted aryl acetic acid derivative delivered the
      ligand 4, which exhibited the highest binding affinity (K(i) = 1.9 nM). The high
      affinity of this ligand provides support to the hypothesis that angiotensin IV
      adopts a gamma-turn in the C-terminal of its bioactive conformation. Ligand (4)
      inhibits both human IRAP and aminopeptidase N-activity and induces proliferation
      of adult neural stem cells at low concentrations. Furthermore, ligand 4 is
      degraded considerably more slowly in membrane preparations than angiotensin IV.
      Hence, it might constitute a suitable research tool for biological studies of the
      (IRAP)/AT(4) receptor.

PMID- 17559065
TI  - Identification of three novel peptides isolated from the venom of the neotropical
      social wasp Polistes major major.
AB  - Three novel peptides designated as PMM1, PMM2, and PMM3 were isolated and
      characterized from the venom of the social wasp Polistes major major, one of the
      most common wasps in the Dominican Republic. By Edman degradation, and MALDI-TOF
      and ESI-QTOF mass spectrometry, the primary sequences of these peptides were
      established as follows: PMM1, H-Lys-Arg-Arg-Pro-Pro-Gly-Phe-Thr-Pro-Phe-Arg-OH
      (1357.77 Da); PMM2, H-Ile-Asn-Trp-Lys-Lys-Ile-Ala-Ser-Ile-Gly-Lys-Glu-Val-Leu-Lys
      Ala-Leu-NH2 (1909.19 Da); and PMM3, H-Phe-Leu-Ser-Ala-Leu-Leu-Gly-Met-Leu-Lys-Asn
      Leu-NH2 (1317.78 Da). The suggested sequences were confirmed by MS analysis of
      peptide fragments obtained by enzymatic digestion. The peptide PMM1 is a lysyl
      arginyl-Thr(6)-bradykinine that belongs to the wasp kinins group. The sequence of
      the PMM2 peptide is unique; it resembles somewhat the tetradecapeptide amides of
      the mastoparan group; however, the chain is extended by three additional amino
      acid residues. The sequence of PMM3 dodecapeptide is homologous to the peptides
      of the wasp chemotactic group.

PMID- 17559066
TI  - Imaging of protein layers with an optical microscope for the characterization of
      peptide microarrays.
AB  - Solid-phase assays play a crucial role today in biological studies. These assays
      are based on the immobilization of probe molecules on a surface, which are able
      to capture specifically soluble receptors. In particular, peptide microarrays
      have emerged as powerful tools in a variety of applications. In this context,
      optical techniques that allow imaging of nanometer-thick biomolecular films, and
      thereby the characterization of microarrays, are of great interest. For this
      purpose, we used a recently disclosed wide-field optical imaging technique of
      surface nanostructures called Sarfus, which is based on the use of a standard
      optical microscope and antireflection substrates. We demonstrate here that this
      technique allows the imaging of the protein layers that result from the specific
      capture of antibodies by arrayed peptide probes with a spatial resolution of 0.45
      microm. The relationship between the thickness of the antibody layer and peptide
      or antibody concentration was examined.

PMID- 17559067
TI  - Delivering multiple anticancer peptides as a single prodrug using lysyl-lysine as
      a facile linker.
AB  - A large 40-residue precursor peptide (propeptide 5) was synthesized by linking
      together four designed anticancer peptide analogs to the neuropeptides:
      vasoactive intestinal peptide, somatostatin, bombesin and substance P, using
      enzyme cleavable lysyl-lysine linkers. On incubation with the enzyme trypsin,
      propeptide 5 was cleaved in a sequence-specific manner at the lysyl-lysine
      residues in the linker to release the individual peptide fragments which were
      identified by LC-MS. Another precursor peptide (propeptide 5a), consisting of two
      of the peptide analogs linked through lysyl-lysine linker, was also
      preferentially cleaved at the Lys-Lys site on incubation with the enzyme trypsin.
      Propeptide 5 showed potent anticancer activity, both in vitro and in vivo, which
      was greater than that of the individual component peptides. The enhanced activity
      suggests that the propeptide is possibly cleaved in the biological system at the
      lysyl-lysine site to yield the individual peptide analogs, which together show a
      synergistic effect. On the basis of these experimental findings, it can be
      concluded that pairs of basic amino acids such as Lys-Lys can be used as facile
      linkers for delivering multiple biologically active peptides.

PMID- 17559068
TI  - Nuclear localization of magphinins, alternative splicing products of the human
      trophinin gene.
AB  - Human magphinin proteins are translation products of differentially spliced
      transcripts from the 5' region of the human trophinin gene (TRO), whose 3' region
      encodes trophinin, a unique cell adhesion molecule involved in human embryo
      implantation. Magphinins belong to the MAGE (melanoma-associated antigen) family,
      and a previous study of mouse magphinins showed their expression in male and
      female germ cells, suggesting a role in germ cell development. Here, we
      characterized the structure and subcellular localization of human magphinins.
      Confocal microscopy analysis of ectopically expressed magphinins revealed that
      magphinin-alpha and -beta localize in the cytoplasm, whereas magphinin-gamma
      lacking the peptide encoded by exon-3 is nuclear. Following Triton X-100
      extraction, DNA digestion, and high salt extraction magphinin-gamma remained
      nuclear, suggesting strong association with the nuclear matrix. A series of
      magphinin-gamma deletion mutants were generated and assayed for localization,
      which showed that the N-terminal region of the MAGE homology domain is necessary
      for nuclear localization. When magphinin-gamma was expressed in NIH3T3 cells,
      cells underwent G1 arrest. These results suggest that human magphinin-gamma
      inhibits cell cycle progression through nuclear activity.

PMID- 17559069
TI  - Claudin-16 is directly phosphorylated by protein kinase A independently of a
      vasodilator-stimulated phosphoprotein-mediated pathway.
AB  - Claudin-16 (CLDN-16) is involved in the paracellular reabsorption of Mg(2+) in
      the thick ascending limb of Henle. The tight junctional localization and Mg(2+)
      transport of CLDN-16 are regulated by cAMP/PKA-dependent phosphorylation. Here,
      we examined whether PKA phosphorylates CLDN-16 in a direct or indirect manner.
      CLDN-16 was stably expressed in Madin-Darby canine kidney (MDCK) cells using a
      Tet-OFF system. The phosphorylation of CLDN-16 is upregulated by fetal calf serum
      (FCS). This phosphorylation was completely inhibited by a PKA inhibitor, N-[2-(p
      bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide dihydrochloride. Without FCS,
      dibutyryl cAMP (DBcAMP) increased the phosphoserine level of CLDN-16 in a
      concentration-dependent manner. The phosphorylated CLDN-16 elicited increases of
      transepithelial electrical resistance (TER) and transepithelial transport of
      Mg(2+). Vasodilator-stimulated phosphoprotein (VASP) was also phosphorylated in
      the presence of FCS or DBcAMP. In the glutathione-S-transferase (GST) pull down
      assay, a cytosolic carboxyl domain of CLDN-16 was associated with PKA, but not
      with VASP. Furthermore, PKA was immunoprecipitated with CLDN-16 in MDCK cells,
      but VASP was not. In cells expressing a dephosphorylated mutant (Ser160Ala) of
      VASP, CLDN-16 was phosphorylated by DBcAMP and was associated with ZO-1, a tight
      junctional-scaffolding protein, without integral cell-cell junctions. We suggest
      that PKA directly phosphorylates CLDN-16, resulting in the localization to tight
      junctions (TJs) and the maintenance of Mg(2+) reabsorption.

PMID- 17559070
TI  - Hypoxia induces epidermal keratinocyte matrix metalloproteinase-9 secretion via
      the protein kinase C pathway.
AB  - Hypoxia promotes keratinocyte migration on wound bed connective tissues and is a
      profound biological signal that transforms a basal keratinocyte, destined to
      differentiate, into a motile cell that is essential for re-epithelialization. In
      this study, we examined the effect of hypoxia on keratinocyte-derived
      collagenases associated with keratinocyte migration. Cells plated on various
      connective tissue matrices under normoxic and hypoxic conditions, demonstrated a
      two-fold increase in the 92 kDa, type IV collagenase (MMP-9) when examined by
      quantitative zymography and ELISA. Western blotting and ELISA demonstrated a two
      fold increase in tissue inhibitor of metalloproteinase (TIMP-1), an enzyme that
      binds to MMP-9 and inhibits its activity. The hypoxia-induced increase in cell
      motility could be inhibited by a neutralizing antibody to MMP-9. Northern
      blotting demonstrated that MMP-9 and TIMP-1 mRNA increased 2.5- to 4-fold, 2-12 h
      after the cells were made hypoxic. The hypoxia-induced changes in MMP-9 and TIMP
      1 were inhibited by staurosporine and bisindolylmaleimide, inhibitors of protein
      kinase C (PKC), but not by inhibitors of tyrosine phosphorylation and the mitogen
      activated protein kinase pathway. Inhibition of PKC also inhibited hypoxia
      induced keratinocyte migration on type I collagen. These data provide evidence
      that hypoxia-induced keratinocyte migration is mediated by increased cellular
      secretion of MMP-9 via the PKC pathway.

PMID- 17559072
TI  - Ab initio study of electronic structure and optical properties of heavy-metal
      azides: TlN3, AgN3, and CuN3.
AB  - Detailed ab initio studies on the electronic structure and optical properties of
      the heavy-metal azides have been performed using density functional theory within
      the generalized gradient approximation. An analysis of band structure, density of
      states, charge transfer, and bond order shows that the heavy-metal azides are
      ionic compounds but have covalent character. The valence bands of AgN3 and CuN3
      are strongly dominated by Ag- and Cu-d, respectively, but that of TlN3 arises
      from the contributions of Tl-s and terminal N-p and not from Tl-d. The real and
      imaginary parts of the dielectric function, adsorption coefficient, and electron
      energy-loss spectra are calculated and compared with available experimental data.

PMID- 17559073
TI  - Ring inversion in 1,4,7 cyclononatriene and analogues: Ab initio and DFT
      calculations and topological analysis.
AB  - The multidimensional conformational potential energy hypersurfaces (PEHSs) for
      cis-cis-cis 1,4,7 cyclononatriene (I), Tribenzocyclononatriene (TBCN) (II), and
      cis-cis-cis cyclic triglycine (III) were comprehensively investigated at the
      Hartree-Fock (HF/6-31G(d)) and density functional theory (B3LYP/6-31G(d,p))
      levels of theory. The equilibrium structures, their relative stability, and the
      transition state (TS) structures involved in the conformational interconversion
      pathways were analyzed. Altogether, four geometries (two low-energy conformations
      and two transition states) were found to be important for a description of the
      conformational features of compounds I-III. B3LYP/aug-cc-pvdz//B3lYP/6-31G(d,p)
      and MP2/6-31G(d,p)//B3LYP/6-31G(d,p) single point calculations predict that the
      conformational interconversion between crown and twist forms requires 14.01,
      26.71, and 17.79 kcal/mol for compounds I, II, and III, respectively, which is in
      agreement with the available experimental data. A topological study of the
      conformational PEHSs of compounds I-III was performed. Our results allow us to
      form a concise idea about the internal intricacies of the PEHSs of compounds I
      III, describing the conformations as well as the conformational interconversion
      process in these hypersurfaces.

PMID- 17559074
TI  - Direct dynamics study on the reaction of acetaldehyde with ozone.
AB  - The hydrogen abstraction reaction of ozone with acetaldehyde has been studied
      theoretically over the temperature range 250-2500 K. Two different reactive sites
      of acetaldehyde molecule, CH(3) and CHO groups have been investigated, and
      results confirm that the CHO group is a highly reactive site. In this study, the
      geometries and harmonic vibrational frequencies of all stationary points are
      calculated at the MPW1K, BHandHLYP, and MPWB1K levels of theory. The minimum
      energy paths (MEPs) were obtained at the MPW1K/6-31+G(d,p) level of theory. To
      refine the energies along the MEPs of each channel, single-point energy
      calculations were performed by a higher-level energy calculation method (denoted
      as HL). The rate constants were evaluated based on the MEPs from the HL method in
      the temperature range 250-2500 K by using the conventional transition state
      theory (TST), the canonical variational transition state theory (CVT), the
      microcanonical variational transition state theory (muVT), the CVT coupled with
      small-curvature tunneling (SCT) correction (CVT/SCT), and the muVT coupled with
      Eckart tunneling correction (muVT/Eckart). The fitted three-parameter Arrhenius
      expressions of the calculated CVT/SCT and muVT/Eckart rate constants of the H
      abstraction from CHO group are k CVT/SCT(T) = 4.92 x 10(-27).T 3.77.e(-7867.0/T)
      and k muVT/Eckart(T) = 2.10 x 10(-27).T(3.90).e(-7706.2/T), respectively. The
      fitted three-parameter Arrhenius expressions of the calculated CVT/SCT and
      muVT/Eckart rate constants of the H abstraction from CH3 group are k(CVT/SCT)(T)
      = 1.27 x 10(-27).T(3.94).e(-14554.1/T) and k muVT/Eckart(T) = 1.62 x 10(
      26).T(3.66).e(-15459.8/T), respectively.

PMID- 17559075
TI  - Multiple field three dimensional quantitative structure-activity relationship (MF
      3D-QSAR).
AB  - A new drug design method, the multiple field three-dimensional quantitative
      structure-activity relationship (MF-3D-QSAR), is proposed. It is a combination
      and development of classical 2D-QSAR and traditional 3D-QSAR. In addition to the
      electrostatic and van der Waals potentials, more potential fields (such as
      lipophilic potential, hydrogen bonding potential, and nonthermodynamic factors)
      are integrated in the MF-3D-QSAR. Meanwhile, a principal component analysis (PCA)
      and iterative double least square (IDLS) technique is developed for predicting
      the bioactivity of query drug candidates. As an example, the MF-3D-QSAR is
      applied to the design of neuraminidase inhibitor and to prove its predictive
      power, and some useful findings are obtained for developing drugs against
      influenza virus.

PMID- 17559076
TI  - Regulation of GLUT3 and glucose uptake by the cAMP signalling pathway in the
      breast cancer cell line ZR-75.
AB  - Increased glucose uptake as a principal energy source is a requirement for the
      continued survival of tumour cells. Facilitative glucose transporter-1 (GLUT1)
      and -3 (GLUT3) have been previously shown to be present and regulated in breast
      cancer cells and are associated with poor patient prognosis. In cancer cells, the
      cAMP secondary messenger pathway is known to potentiate described glucose
      transporter activators and regulate cell fate. However, no regulation of the
      glucose transporters in breast cancer cells by cAMP has previously been examined.
      Herein, we determined in the well-characterized breast cancer cell line ZR-75, if
      the cAMP analogue 8-br-cAMP was capable of regulating GLUT1 and GLUT3 expression
      and thus glucose uptake. We demonstrated that 8-br-cAMP transiently up-regulates
      GLUT3 mRNA levels. The use of actinomycin-D and the cloning of 1,200 bp upstream
      of the human GLUT3 promoter demonstrated that this regulation was
      transcriptional. Immunocytochemistry and Western blotting confirmed that the
      increase in mRNA was reflected by an increase in protein levels. No notable
      regulation of GLUT1 in the presence of 8-br-cAMP was detected. Finally, we
      determined using the non-metabolizable glucose analogue 2-DOG if this up
      regulation in GLUT3 increased glucose uptake. We observed the presence of two
      uptake components, one corresponding to the Km of GLUT1/4 and the other to GLUT3.
      A doubling in the uptake velocity was observed only at the Km corresponding to
      GLUT3. In conclusion, we demonstrate and characterize for the first time, an up
      regulation of GLUT3 mRNA, protein and glucose uptake by the cAMP pathway in
      breast cancer cells.

PMID- 17559071
TI  - Liver regeneration.
AB  - Liver regeneration after partial hepatectomy is a very complex and well
      orchestrated phenomenon. It is carried out by the participation of all mature
      liver cell types. The process is associated with signaling cascades involving
      growth factors, cytokines, matrix remodeling, and several feedbacks of
      stimulation and inhibition of growth related signals. Liver manages to restore
      any lost mass and adjust its size to that of the organism, while at the same time
      providing full support for body homeostasis during the entire regenerative
      process. In situations when hepatocytes or biliary cells are blocked from
      regeneration, these cell types can function as facultative stem cells for each
      other.

PMID- 17559077
TI  - Anti-apoptotic Bcl-2 enhancing requires FGF-2/FGF receptor 1 binding in mouse
      osteoblasts.
AB  - In this study, we investigated the role of prostaglandin F2alpha (PGF2alpha) in
      mouse osteoblast survival and the function of fibroblast growth factor 2 (FGF-2)
      and fibroblast growth factor receptor 1 (FGFR1) in this process. In particular,
      for the first time, we demonstrated that PGF2alpha increased osteoblast survival
      in a dose-dependent manner and we showed that the effect is correlated with an
      increase in Bcl-2/Bax ratio. Furthermore, we demonstrated that PGF2alpha caused a
      decrement of the active caspases 9 and 3. By blocking FGF-2 with the specific
      neutralizing antibody and by depletion of FGFR1 gene with a specific siRNA, we
      showed that FGFR1 and FGF-2 are critical for the increment of Bcl-2/Bax ratio and
      the decrement of the active caspases 9 and 3, induced by PGF2alpha. Moreover,
      transmission electron microscopy studies showed that PGF2alpha increased binding
      of FGF-2 and FGFR1 and co-localization of reactive sites at plasma membrane
      level. In conclusion, we report a novel mechanism in which PGF2alpha induces FGF
      2 binding to its specific cell surface receptor 1 leading to a cascade pathway
      that culminates with increased mouse osteoblast survival.

PMID- 17559078
TI  - Childhood intracranial ependymoma: twenty-year experience from a single
      institution.
AB  - BACKGROUND: Because few large studies of pediatric ependymoma treatment are
      available, the authors believed that a retrospective review of treatment outcomes
      from a single institution would yield potentially valuable information regarding
      potential prognostic factors. In this article, they report their 20-year
      institutional experience with this disease. METHODS: Medical records were reviews
      of patients with intracranial ependymoma who received their initial treatment at
      the Children's Hospital of Philadelphia (CHOP)/Hospital of the University of
      Pennsylvania (HUP) between January 1980 and December 2000. Of the 61 patients who
      were identified, 49 patients underwent primary therapy at CHOP/HUP and formed the
      basis for the study. Actuarial overall survival (OS) and progression-free
      survival (PFS) were determined by the Kaplan-Meier method. Univariate and
      multivariate analyses were performed using the log-rank test and Cox proportional
      hazards models. RESULTS: With median follow-up of 110.2 months, the 5-year OS and
      PFS rates were 66.2% and 40.7%, respectively. Older age and higher radiation dose
      significantly predicted for improved OS. Anaplastic histology predicted for
      decreased PFS. Cervical spinal cord extension resulted in decreased OS primarily
      caused by failures outside the primary site. Patients who had a favorable
      prognosis (aged >/=3 years, no dissemination or cord extension, complete
      resection, and radiation dose >/=54 grays [Gy]) had 5-year OS and PFS rates of
      83.1% and 60.6%, respectively. CONCLUSIONS: In this study of patients with
      pediatric intracranial ependymoma, OS and PFS rates were concordant with the
      rates published in other modern series. The finding of a dose response up to 54
      Gy supported the current trend toward dose escalation. Tumor extension to the
      cervical spine was identified as a predictor for failure outside of the primary
      site. Although the survival rates were encouraging, there is still significant
      room for improvement in the management of this disease.

PMID- 17559079
TI  - Induction of Id2 expression by cardiac transcription factors GATA4 and Nkx2.5.
AB  - Inhibitor of differentiation/DNA binding (Id) proteins function as a regulator of
      helix-loop-helix proteins participating in cell lineage commitment and
      differentiation. Here, we observed a marked induction of Id2 during cardiomyocyte
      differentiation from P19CL6 murine embryonic teratocarcinoma stem cells,
      prompting us to investigate the upstream regulatory mechanism of Id2 induction.
      Computer analysis of Id2 promoter and subsequent electrophoretic mobility shift
      assay revealed several binding sites for GATA4 and Nkx2.5 within the Id2
      promoter. By further deletion and mutation analysis of the respective binding
      site, we identified that two motifs located at -497/-502 and -264/-270 were
      functionally important for Id2 promoter activation by GATA4 and Nkx2.5,
      respectively. Overexpression of GATA4 and/or Nkx2.5 induced not only Id2 promoter
      activity but also Id2 protein expression. Additionally, Id proteins significantly
      inhibit the GATA4 and Nkx2.5-dependent transcription, suggesting Id proteins may
      play a regulatory role in cardiogenesis. Collectively, our results demonstrate
      that GATA4 and Nkx2.5 could be one of the upstream regulators of Id2.

PMID- 17559080
TI  - Embryonic undifferentiated cells show scattering activity on a surface coated
      with immobilized E-cadherin.
AB  - Rearrangement of cell-cell adhesion is a critical event in embryonic development
      and tissue formation. We investigated the regulatory function of E-cadherin, a
      key adhesion protein, in the developmental process by using E-cadherin/IgG Fc
      fusion protein as an adhesion matrix in cell culture. F9 embryonal carcinoma
      cells usually form colonies when cultured on gelatin or fibronectin matrices.
      However, F9 cells cultured on the E-cadherin/IgG Fc fusion protein matrix formed
      a scattered distribution, with a different cytoskeletal organization and E
      cadherin-rich protrusions that were regulated by Rac1 activity. The same
      scattering activity was observed in P19 embryonal carcinoma cells. In contrast,
      three types of differentiated cells, NMuMG mammary gland cells, MDCK kidney
      epithelial cells, and mouse primary isolated hepatocytes, did not show the
      scattering activity observed in F9 and P19 cells. These results suggest that
      migratory behavior on an E-cadherin-immobilized surface is only observed in
      embryonic cells, and that the regulatory mechanisms underlying E-cadherin
      mediated cell adhesion vary with the state of differentiation.

PMID- 17559081
TI  - Ang II and EGF synergistically induce COX-2 expression via CREB in intestinal
      epithelial cells.
AB  - Cyclooxygenase (COX)-2 derived prostaglandins (PGs) play a major role in
      intestinal inflammation and colorectal carcinogenesis. Because COX-2 is the rate
      limiting step in the production of PGs, mechanisms that regulate COX-2 expression
      control PG production in the cell. Using the non-tumorigenic, rat intestinal
      epithelial cell, IEC-18, we demonstrate that co-activation of endogenously
      expressed AT(1) receptor and EGFR resulted in synergistic expression of COX-2
      mRNA and protein involving transcriptional and post-transcriptional mechanisms.
      Ang II and EGF induced transient phosphorylation of ERK, p38(MAPK) and CREB. Co
      stimulation with Ang II and EGF prolonged phosphorylation of ERK, p38(MAPK), and
      CREB. The p38(MAPK) selective inhibitor, SB202190, but not the MEK selective
      inhibitor, PD98059, or the EGFR kinase inhibitor, AG1478, inhibited Ang II
      dependent COX-2 expression and CREB phosphorylation. EGF-dependent COX-2
      expression and CREB phosphorylation were inhibited by SB202190, PD98059, and
      AG1478. Inhibition of CREB expression using two separate RNAi methods blocked COX
      2 expression by Ang II and EGF. Expression of a dominant negative CREB mutant
      inhibited Ang II- and EGF-dependent induction of the COX-2 promoter. Ang II
      induced luciferase expression in cells transfected with the CRE-luc reporter
      vector and cells co-transfected with Gal4-luc reporter vector and a Gal4-CREB
      expression vector. Chromatin immunoprecipitation assays demonstrated CREB binding
      to the proximal rat COX-2 promoter region containing a CRE cis-acting element.
      These results indicate that co-stimulation with Ang II and EGF synergistically
      induced COX-2 expression in these intestinal epithelial cells through p38(MAPK)
      mediated signaling cascades that converge onto CREB.

PMID- 17559082
TI  - Immunophenotypic changes of human articular chondrocytes during monolayer culture
      reflect bona fide dedifferentiation rather than amplification of progenitor
      cells.
AB  - In this study, a time-course comparison of human articular chondrocytes (HAC) and
      bone marrow-derived mesenchymal stem cells (MSC) immunophenotype was performed in
      order to determine similarities/differences between both cell types during
      monolayer culture, and to identify HAC surface markers indicative of
      dedifferentiation. Our results show that dedifferentiated HAC can be
      distinguished from MSC by combining CD14, CD90, and CD105 expression, with
      dedifferentiated HAC being CD14+/CD90bright/CD105dim and MSC being CD14
      /CD90dim/CD105bright. Surface markers on MSC showed little variation during the
      culture, whereas HAC showed upregulation of CD90, CD166, CD49c, CD44, CD10, CD26,
      CD49e, CD151, CD51/61, and CD81, and downregulation of CD49a, CD54, and CD14.
      Thus, dedifferentiated HAC appear as a bona fide cell population rather than a
      small population of MSC amplified during monolayer culture. While most of the HAC
      surface markers showed major changes at the beginning of the culture period
      (Passage 1-2), CD26 was upregulated and CD49a downregulated at later stages of
      the culture (Passage 3-4). To correlate changes in HAC surface markers with
      changes in extracellular matrix gene expression during monolayer culture, CD14
      and CD90 mRNA levels were combined into a new differentiation index and compared
      with the established differentiation indices based on the ratios of mRNA levels
      of collagen type II to I (COL2/COL1) and of aggrecan to versican (AGG/VER). A
      correlation of CD14/CD90 ratio at the mRNA and protein level with the AGG/VER
      ratio during HAC dedifferentiation in monolayer culture validated CD14/CD90 as a
      new membrane and mRNA based HAC differentiation index.

PMID- 17559083
TI  - Modulation of the heteromeric Kir4.1-Kir5.1 channel by multiple neurotransmitters
      via Galphaq-coupled receptors.
AB  - The heteromeric Kir4.1-Kir5.1 channel is a candidate sensing molecule for central
      CO(2) chemoreception. Since central CO(2) chemoreception is subject to neural
      modulations, we performed studies to test the hypothesis that the Kir4.1-Kir5.1
      channel is modulated by the neurotransmitters critical for respiratory control,
      including serotonin (5-HT), substance-P (SP), and thyrotropin releasing hormone
      (TRH). The heteromeric Kir4.1-Kir5.1 channel was strongly inhibited by SP, TRH,
      and 5-HT when expressed in Xenopus oocytes, whereas these neurotransmitters had
      no effect on the homomeric Kir4.1 channel. Such an inhibition was dose-dependent
      and relied on specific G(alphaq)-protein-coupled receptors and protein kinase C
      (PKC). No direct interaction of the channel with G-proteins was found. Channel
      sensitivity to CO(2)/pH was not compromised with the inhibition by these
      neurotransmitters, as the channel remained to be inhibited by acidic pH following
      an exposure to the neurotransmitters. The firing rate of CO(2)-sensitive
      brainstem neurons cultured in microelectrode arrays was augmented by SP or a 5
      HT2A receptor agonist, which was blocked by PKC inhibitors suggesting that PKC
      underscores the inhibitory effect of SP and 5-HT in cultured brainstem neurons as
      well. Immunostaining showed that both Kir4.1 and Kir5.1 proteins were co
      localized in the cultured brainstem neurons. These results therefore indicate
      that the heteromeric Kir4.1-Kir5.1 channel is modulated by the neurotransmitters
      critical for respiratory control, suggesting a novel neuromodulatory mechanism
      for the chemosensitivity of brainstem neurons to elevated PCO(2) and acidic pH.

PMID- 17559084
TI  - Polyalanine expansions might not result from unequal crossing-over.

PMID- 17559085
TI  - The transcriptional coactivator and acetyltransferase p300 in fibroblast biology
      and fibrosis.
AB  - The transcriptional coactivator p300 is a ubiquitous nuclear phosphoprotein and
      transcriptional cofactor with intrinsic acetyltransferase activity. p300 controls
      the expression of numerous genes in cell-type and signal-specific manner, and
      plays a pivotal role in cellular proliferation, apoptosis, and embryogenesis. By
      catalyzing acetylation of histones and transcription factors, p300 plays a
      significant role in epigenetic regulation. Recent evidence suggests that abnormal
      p300 function is associated with deregulated target gene expression, and is
      implicated in inflammation, cancer, cardiac hypertrophy, and genetic disorders
      such as the Rubinstein-Taybi syndrome. The activity of p300 is regulated at
      multiple levels, including developmental stage-specific expression, post
      translational modifications, subcellular localization, and cell-type and gene
      specific interactions with transcription factors. Although p300 has been
      investigated extensively in epithelial and hematopoietic cells, its role in
      fibroblast biology and tissue repair has received little attention to date.
      Recent studies implicate p300 in the regulation of collagen synthesis by
      transforming growth factor-beta (TGF-beta). Both the acetyltransferase activity
      of p300 and its inducible interaction with Smad3 are essential for mediating TGF
      beta-induced stimulation of collagen synthesis. As a signal integrator whose
      availability for intracellular interactions with transcription factors is
      strictly limiting, p300 mediates the antagonistic regulation of TGF-beta-induced
      collagen synthesis by IFN-gamma and TNF-alpha via intracellular competition for
      limiting amount of p300. Significantly, p300 is itself a direct transcriptional
      target of TGF-beta in normal fibroblasts, and its levels are significantly
      elevated in fibrotic lesions as well as in experimental models of fibrosis. The
      emerging appreciation of the importance of p300 in extracellular matrix (ECM)
      remodeling and fibrosis and novel insights concerning the regulation, mechanism
      of action, and significance of p300 in fibroblast biology are discussed in this
      minireview.

PMID- 17559086
TI  - Molecular heterogeneity in fetal forms of type II lissencephaly.
AB  - Type II lissencephaly (type II LIS) is a group of autosomal recessive congenital
      muscular dystrophies (CMD) associated with defects in alpha-DG O-glycosylation,
      which comprises Walker-Warburg syndrome, Fukuyama cerebral and muscular
      dystrophy, or muscle-eye-brain disease. The most severe forms of these diseases
      often have a fetal presentation and lead to a pregnancy termination. We report
      here the first molecular study on fetal type II LIS in a series of 47 fetuses
      from 41 unrelated families. Sequencing of the different genes known to be
      involved in alpha-DG O-glycosylation allowed the molecular diagnosis in 22
      families: involvement of POMT1 was demonstrated in 32% of cases, whereas POMGNT1
      and POMT2 were incriminated in 15% and in 7% of cases, respectively. We found 30
      different mutations in these three genes, 25 were described herein for the first
      time, 15 in POMT1, and five in POMT2 and POMGNT1. Despite sequencing of FKRP,
      FCMD, and LARGE, no definitive molecular diagnosis could be made for the other
      half of our cases. Preliminary results concerning genotype-phenotype correlations
      show that the choice of the first gene sequenced should depend on the clinical
      severity of the type II LIS; POMT1 and POMT2 for severest clinical picture and
      POMGNT1 for milder disease. The other genes, FKRP, FCMD, and LARGE, seem not to
      be implicated in the fetal form of CMD.

PMID- 17559087
TI  - Depression, desperation, and suicidal ideation in college students: results from
      the American Foundation for Suicide Prevention College Screening Project at Emory
      University.
AB  - The objective of this investigation was to examine suicidal ideation and
      depression in undergraduate college students who participated in the American
      Foundation for Suicide Prevention-sponsored College Screening Project at Emory
      University. The principal measure of depressive symptoms was the nine-item
      depression module from the Patient Health Questionnaire (PHQ-9). Additional
      questions were focused on current suicidal ideation, past suicide attempts, and
      episodes of deliberate self-harm and on symptoms of anxiety and distress. Seven
      hundred and twenty-nine students participated over a 3-school-year interval (2002
      2005). Most notably, 11.1% of the students endorsed current (past 4 weeks)
      suicidal ideation and 16.5% had a lifetime suicide attempt or self-injurious
      episode. Students with current suicidal ideation had significantly higher
      depression symptom severity than those without suicidal ideation (t = -9.34, df =
      706, P<.0001, d = 1.9), and 28.5% of the students with PHQ-9 scores of 15 or
      higher reported suicidal ideation compared to 5.7% of those with lower scores
      (chi(2) = 56.29, df = 1, P<.0001, two-tailed). Suicidal ideation was prominently
      associated with symptoms of desperation (odds ratio 2.6, 95% CI 1.5-4.6, P<.001).
      The vast majority of students with moderately severe to severe depression (85%)
      or current suicidal ideation (84%) were not receiving any psychiatric treatment
      at the time of assessment. These results suggest that there is a strong
      relationship between severity of depressive symptoms and suicidal ideation in
      college students, and that suicidal feelings and actions are relatively common in
      this group. This underscores the need to provide effective mental health outreach
      and treatment services to this vulnerable population. As this analysis was based
      on data collected at a single institution, the results may not be representative
      of all college students or young adults.

PMID- 17559088
TI  - Auditory efferent feedback system deficits precede age-related hearing loss:
      contralateral suppression of otoacoustic emissions in mice.
AB  - The C57BL/6J mouse has been a useful model of presbycusis, as it displays an
      accelerated age-related peripheral hearing loss. The medial olivocochlear
      efferent feedback (MOC) system plays a role in suppressing cochlear outer hair
      cell (OHC) responses, particularly for background noise. Neurons of the MOC
      system are located in the superior olivary complex, particularly in the
      dorsomedial periolivary nucleus (DMPO) and in the ventral nucleus of the
      trapezoid body (VNTB). We previously discovered that the function of the MOC
      system declines with age prior to OHC degeneration, as measured by contralateral
      suppression (CS) of distortion product otoacoustic emissions (DPOAEs) in humans
      and CBA mice. The present study aimed to determine the time course of age changes
      in MOC function in C57s. DPOAE amplitudes and CS of DPOAEs were collected for
      C57s from 6 to 40 weeks of age. MOC responses were observed at 6 weeks but were
      gone at middle (15-30 kHz) and high (30-45 kHz) frequencies by 8 weeks.
      Quantitative stereological analyses of Nissl sections revealed smaller neurons in
      the DMPO and VNTB of young adult C57s compared with CBAs. These findings suggest
      that reduced neuron size may underlie part of the noteworthy rapid decline of the
      C57 efferent system. In conclusion, the C57 mouse has MOC function at 6 weeks,
      but it declines quickly, preceding the progression of peripheral age-related
      sensitivity deficits and hearing loss in this mouse strain.

PMID- 17559089
TI  - Opposing functions of CREB and MKK1 synergistically regulate the geometry of
      dendritic spines in visual cortex.
AB  - Most excitatory inputs onto pyramidal neurons are made on dendritic spines. The
      geometry of dendritic spines modulates synaptic function; yet we know little
      regarding the molecular signals that regulate spine geometry. Here we report that
      neurons coordinately regulate the geometry of spines to compensate for
      variability in spine number, by a process requiring the transcription factor CREB
      and the kinase MKK1. We find that CREB function is induced, whereas MKK1 is
      inhibited, by activity blockade. To obtain evidence that CREB and MKK1 regulate
      dendritic spine geometry in vivo, we coexpressed green fluorescent protein and
      dominant negative CREB or MKK1 in pyramidal neurons of the intact rat visual
      cortex. Spines on apical dendrites of layer 3 neurons were then characterized by
      confocal microscopy. We find that CREB and MKK1 regulate spine geometry in
      opposite ways. MKK1 is required to reduce spine head size when spine density is
      high, whereas CREB is required to enlarge spines when spine density is low. Our
      data suggest that CREB and MKK1 might function as complementary negative feedback
      mechanisms to maintain synaptic drive within bounds.

PMID- 17559091
TI  - Non-overlapping expression patterns of the clustered Dll-A/B genes in the
      ascidian Ciona intestinalis.
AB  - The Ci-Dll-A and Ci-Dll-B genes of Ciona intestinalis are arranged in a
      convergently transcribed gene cluster. This genomic arrangement is similar to
      that of the multiple bigene clusters of the Dlx homologs in vertebrates. Analysis
      of whole genome sequences showed that linkage to the Hox cluster is conserved
      with the vertebrate clusters. Phylogenetic analysis supports gene trees
      consistent with homology of the ascidian and vertebrate Dlx clusters, and in
      combination with the apparent conservation of genomic arrangement, it is
      concluded that the ascidian cluster is most likely homologous with the vertebrate
      clusters. Using whole-mount in situ hybridization, Ci-Dll-B transcripts were
      detected in all ectodermal lineages through gastrulation. Expression is radically
      downregulated in the neurula with detectable expression disappearing around the
      time that Ci-Dll-A expression appears in the anterior ectoderm. By the late
      tailbud stage Ci-Dll-Atranscripts were detected in the bilateral atrial primordia
      and persisted in the atrial rudiments to the larval stage, suggesting a role in
      development of these neural placode-like structures. This non-overlapping
      expression contradicts a common pattern seen in clustered genes, where as
      adjacent paralogs have largely overlapping expression domains. Enhancer sharing
      is often proposed as an explanation for the overlapping expression of gene
      cluster members. For this case of non-overlapping expression a model is proposed
      in which repressors acting at different stages override one or more shared
      enhancers. The enhancer sharing prevents breakup of the cluster while the
      independent temporal suppressors hide the presence of the shared enhancers.

PMID- 17559090
TI  - Drebrin a content correlates with spine head size in the adult mouse cerebral
      cortex.
AB  - Synaptic activities alter synaptic strengths at the axospinous junctions, and
      such changes are often accompanied by changes in the size of the postsynaptic
      spines. We have been exploring the idea that drebrin A, a neuron-specific actin
      binding protein localized on the postsynaptic side of excitatory synapses, may be
      a molecule that links synaptic activity to the shape and content of spines. Here,
      we performed electron microscopic immunocytochemistry with the nondiffusible gold
      label to explore the relationship among levels of drebrin A, the NR2A subunit of
      N-methyl-D-aspartate receptors, and the size of spines in the perirhinal cortex
      of adult mouse brains. In contrast to the membranous localization within neonatal
      spines, most immunogold particles for drebrin A were localized to the cytoplasmic
      core region of spines in mature spines. This distribution suggests that drebrin
      within adult spines may reorganize the F-actin network at the spine core, in
      addition to its known neonatal role in spine formation. Drebrin A-immunopositive
      (DIP) spines exhibited larger spine head areas and longer postsynaptic densities
      (PSDs) than drebrin A-immunonegative (DIN) spines (P < 0.001). Furthermore, spine
      head area and PSD lengths correlated positively with drebrin A levels (r = 0.47
      and 0.40). The number of synaptic NR2A immunolabels was also higher in DIP spines
      than in DIN spines, whereas their densities per unit lengths of PSD were not
      significantly different. These differences between the DIP and the DIN spines
      indicate that spine sizes and synaptic protein composition of mature brains are
      regulated, at least in part, by drebrin A levels.

PMID- 17559092
TI  - A small dopamine permeability of storage vesicle membranes and end product
      inhibition of tyrosine hydroxylase are sufficient to explain changes occurring in
      dopamine synthesis and storage after inhibition of neuron firing.
AB  - Computer simulations of dopamine (DA) regulation at a striatal varicosity were
      developed to determine basic principles that explain the pattern of changes in
      level of neurotransmitter and its rate of synthesis and metabolism when DA neuron
      firing is inhibited. The models suggest that DA synthesis is normally at a slower
      rate because of end-product inhibition of tyrosine hydroxylase (TH) by cytosolic
      DA. The vast majority of DA in the cytosol arrives there via "recycling"--DA that
      was released during an exocytotic event is moved into the cytosol via the
      dopamine transporter (DAT). When neuronal firing is inhibited, the amount of
      cytosolic DA markedly decreases as there is no recycling. The rate of DA
      synthesis then increases because of the loss of end-product inhibition of TH. The
      newly synthesized DA is stored in vesicles, thus increasing the total amount of
      DA in the vesicles. A small amount of DA is continually leaking out of vesicles,
      and the amount leaking out increases proportionally to the amount of DA in
      vesicles. When the amount of DA leaking out balances the amount being stored by
      the vesicular monoamine transporter, DA accumulates in the cytosol. The
      accumulating DA inhibits TH activity, and the system enters a steady state
      condition characterized by approximately double the normal amount of DA in
      vesicles and approximately normal rate of DA synthesis and metabolism.

PMID- 17559093
TI  - Effects of increased endogenous serotonin on the in vivo binding of [11C]DASB to
      serotonin transporters in conscious monkey brain.
AB  - Using a combination of positron emission tomography (PET) and the microdialysis
      technique, the effects of increased endogenous serotonin (5-hydroxytryptamine; 5
      HT) on the binding of [(11)C]DASB to 5-HT transporters (5-HTT) were investigated
      in the conscious monkey brain. Five rhesus monkeys (Macaca mulatta) were scanned
      with [(11)C]DASB under the control condition and the increased endogenous 5-HT
      condition, in which 5-hydroxy-L-tryptophan (5-HTP) was administered (20 mg/kg,
      i.v.) before the PET scan. Compared with the control scan, the 5-HTP
      administration significantly decreased the binding potential (BP) (BP =
      B(max)/K(d)) of [(11)C]DASB in several brain regions. The mean % decrease of BP
      was biggest in the caudate and putamen. Two monkeys were scanned with [(11)C]5
      HTP to assess the amino acid decarboxylase (AADC) activity in the brain,
      resulting in the high activity in the caudate and putamen. Microdialysis
      measurements showed that although 5-HTP administration (20 mg/kg, i.v.) increased
      the extracellular 5-HT levels in both the prefrontal cortex and caudate, the
      increase of the 5-HT level in the caudate was 27 times higher than that in the
      prefrontal cortex. These results suggest that the caudate and putamen, both of
      which show high AADC activity, convert 5-HTP to 5-HT at a high rate, and the
      increased 5-HT competes with [(11)C]DASB for the 5-HTT.

PMID- 17559094
TI  - Central nervous system distribution of the transcription factor Phox2b in the
      adult rat.
AB  - Phox2b is required for development of the peripheral autonomic nervous system and
      a subset of cranial nerves and lower brainstem nuclei. Phox2b mutations in man
      cause diffuse autonomic dysfunction and deficits in the automatic control of
      breathing. Here we study the distribution of Phox2b in the adult rat hindbrain to
      determine whether this protein is selectively expressed by neurons involved in
      respiratory and autonomic control. In the medulla oblongata, Phox2b
      immunoreactive nuclei were present in the dorsal vagal complex, intermediate
      reticular nucleus, dorsomedial spinal trigeminal nucleus, nucleus ambiguus,
      catecholaminergic neurons, and retrotrapezoid nucleus (RTN). Phox2b was expressed
      by both central excitatory relays of the sympathetic baroreflex (nucleus of the
      solitary tract and C1 neurons) but not by the inhibitory relay of this reflex.
      Phox2b was absent from the ventral respiratory column (VRC) caudal to RTN and
      rare within the parabrachial nuclei. In the pons, Phox2b was confined to
      cholinergic efferent neurons (salivary, vestibulocochlear) and noncholinergic
      peritrigeminal neurons. Rostral to the pons, Phox2b was detected only in the
      oculomotor complex. In adult rats, Phox2b is neither a comprehensive nor a
      selective marker of hindbrain autonomic pathways. This marker identifies a subset
      of hindbrain neurons that control orofacial movements (dorsomedial spinal
      trigeminal nucleus, pontine peritrigeminal neurons), balance and auditory
      function (vestibulocochlear efferents), the eyes, and both divisions of the
      autonomic efferent system. Phox2b is virtually absent from the respiratory rhythm
      and pattern generator (VRC and dorsolateral pons) but is highly expressed by
      neurons involved in the chemical drive and reflex regulation of this oscillator.

PMID- 17559095
TI  - Post-pubertal emergence of alterations in locomotor activity in stop null mice.
AB  - Overt schizophrenia is preceded by a prodromal phase during which juvenile
      patients display attenuated schizophrenia-related symptoms. Here, we have looked
      for evidence of a prodromal phase in juvenile STOP null mice, which, during
      adulthood, imitate features of schizophrenia. We have principally examined
      locomotor activity, which is abnormal in adult STOP null mice, and its apparent
      relationship with perturbed glutamatergic and dopaminergic transmission. When
      compared to corresponding wild-type mice, juvenile STOP null mice did not exhibit
      the basal hyperlocomotion or locomotor hypersensitivity to mild stress observed
      in adult mice. Juvenile STOP null mice also lacked disturbed locomotor
      sensitivity to MK-801, which was evident in adult mice. In contrast, juvenile
      STOP null mice exhibited a similar hypersensitivity to amphetamine as that found
      in adult mice. Thus, STOP null mice exhibited both a progression of locomotor
      activity defects over time and subtle alterations in the prepubertal period. We
      suggest that the pattern of locomotor disturbances observed in this study is
      related to altered dopaminergic reactivity in juvenile mice without major
      disturbance in glutamatergic transmission, whereas both neurotransmitter systems
      are impaired in adult mice.

PMID- 17559096
TI  - Time-course of change in [11C]carfentanil and [11C]raclopride binding potential
      after a nonpharmacological challenge.
AB  - Positron Emission Tomography (PET) with appropriate radiotracers and
      quantification methods allows the detection of changes in endogenous
      neurotransmission by determine the reduction in the binding potential (BP) of
      receptors before and after experimental challenges. These have typically employed
      psychostimulants and PET with dopamine (DA) receptor radiotracers. However,
      reductions in BP persist far beyond the increases in the release of the
      endogenous neurotransmitter, an effect ascribed to receptor internalization and
      recycling, a possible confound in repeated studies. Here we examined the time
      course of changes in BP during a nonpharmacological challenge, moderate levels of
      sustained pain, shown to induce robust reductions in micro-opioid and DA D2 BP,
      as measured with [(11)C]carfentanil and [(11)C]raclopride. It was hypothesized
      that, contrary to pharmacological probes, the use of a more "physiological"
      stimulus would not be associated with persistent changes in the BP measures. The
      pain challenge was associated with reductions in micro-opioid receptor BP in
      several cortical and subcortical regions. These did not persist in a subsequent
      scan. Similar results were obtained for DA D2 receptor BP, where the pain
      challenge induced significant reductions in the caudate nucleus. These data
      demonstrate that changes in receptor BP induced by a nonpharmacological challenge
      did not persist into subsequent scans. They further suggest differences in the
      effect of pharmacological and nonpharmacological probes on PET BP measures. These
      may reflect varying levels of change in receptor affinity, receptor
      internalization, and recycling depending on the type of challenge employed.

PMID- 17559097
TI  - Suppressive effect of paroxetine, a selective serotonin uptake inhibitor, on
      tetrahydrobiopterin levels and dopamine as well as serotonin turnover in the
      mesoprefrontal system of mice.
AB  - Tetrahydrobiopterin (BH(4)) is a coenzyme of tyrosine hydroxylase (TH) and
      tryptophan hydroxylase (TPH), which are rate-limiting enzymes of monoamine
      biosynthesis. According to the monoamine hypothesis of depression,
      antidepressants will restore the function of the brain monoaminergic system and
      the BH(4) concentration. In the present study, we investigated the effect of
      paroxetine, a selective serotonin reuptake inhibitor (SSRI), on the BH(4) levels
      and dopamine (DA) and serotonin (5-HT) turnover in the mesoprefrontal system,
      incorporating two risk factors of depression, social isolation and acute
      environmental change. Male ddY mice (8W) were divided into two housing groups,
      i.e., group-housing (eight animals per cage; 28 days), and isolation-housing (one
      per cage; 28 days), being p.o.-administered paroxetine (5 or 10 mg/kg; days 15
      28), and exposed to a 20-min novelty stress (day 28). The levels of BH(4), DA,
      homovanilic acid (HVA), 5-HT, and 5-hydroxyindoleacetic acid (5-HIAA) were
      measured in the prefrontal cortex and midbrain. In both the regions, novelty
      stress significantly increased BH(4) levels under the isolation-housing
      condition, whereas these levels were decreased under the group-housing condition.
      Thus, social isolation altered the neurochemical response to novelty stress.
      Paroxetine significantly decreased BH(4) levels under the isolation-housing
      condition, whereas decreased HVA/DA and 5-HIAA/5-HT ratios were observed under
      the group-housing condition. Thus, social isolation may have influenced the
      suppressive effects of paroxetine on BH(4) levels as well as exerted an influence
      on DA and 5-HT turnover. We replicated our recent findings that SSRI,
      fluvoxamine, suppressed BH(4) levels, as well as DA and 5-HT turnover in the
      mouse mesoprefrontal system.

PMID- 17559098
TI  - Spatiotemporal analyses of interactions between entorhinal and CA1 projections to
      the subiculum in rat brain slices.
AB  - The subiculum and the entorhinal cortex (EC) are important structures in
      processing and transmitting information between the neocortex and the
      hippocampus. The subiculum potentially receives information from the EC through
      two routes. In addition to a direct projection from EC to the subiculum, there is
      an indirect polysynaptic connection. The latter uses a number of possible
      pathways, which all converge onto the final projection from the hippocampal field
      CA1 to the subiculum. In this series of experiments we investigated to what
      extent activity in both pathways influences population activity of subicular
      neurons. We used voltage sensitive dyes in combined hippocampal-EC slices of the
      rat to measure the spatio-temporal activity patterns. To activate the two inputs
      to the subiculum, stimulation electrodes were placed in the stratum oriens/alveus
      of CA1 and in layer III of the medial EC. The response patterns evoked in the
      subiculum after electrical stimulation of each of these input pathways separately
      were compared with the response patterns after simultaneous stimulation of both
      areas (medial EC + CA1). A comparison of the computed added responses of the two
      individual stimulations with the measured responses after simultaneous
      stimulation suggests that both inputs are linearly added in the subiculum with
      very little nonlinear interactions. This strongly suggests that in the subiculum
      interaction at a single cell level of the direct and the indirect pathways from
      the EC is an unlikely scenario.

PMID- 17559099
TI  - G-protein-coupled GABAB receptors inhibit Ca2+ channels and modulate transmitter
      release in descending turtle spinal cord terminal synapsing motoneurons.
AB  - Presynaptic gamma-aminobutyric acid type B receptors (GABA(B)Rs) regulate
      transmitter release at many central synapses by inhibiting Ca(2+) channels.
      However, the mechanisms by which GABA(B)Rs modulate neurotransmission at
      descending terminals synapsing on motoneurons in the spinal cord remain
      unexplored. To address this issue, we characterized the effects of baclofen, an
      agonist of GABA(B)Rs, on the monosynaptic excitatory postsynaptic potentials
      (EPSPs) evoked in motoneurons by stimulation of the dorsolateral funiculus (DLF)
      terminals in a slice preparation from the turtle spinal cord. We found that
      baclofen depressed neurotransmission in a dose-dependent manner (IC(50) of
      approximately 2 microM). The membrane time constant of the motoneurons did not
      change, whereas the amplitude ratio of the evoked EPSPs in response to a paired
      pulse was altered in the presence of the drug, suggesting a presynaptic
      mechanism. Likewise, the use of N- and P/Q-type Ca(2+) channel antagonists (omega
      conotoxin GVIA and omega-agatoxin IVA, respectively) also depressed EPSPs
      significantly. Therefore, these channels are likely involved in the Ca(2+) influx
      that triggers transmitter release from DLF terminals. To determine whether the N
      and P/Q channels were regulated by GABA(B)R activation, we analyzed the action of
      the toxins in the presence of baclofen. Interestingly, baclofen occluded omega
      conotoxin GVIA action by approximately 50% without affecting omega-agatoxin IVA
      inhibition, indicating that the N-type channels are the target of GABA(B)Rs.
      Lastly, the mechanism underlying this effect was further assessed by inhibiting G
      proteins with N-ethylmaleimide (NEM). Our data show that EPSP depression caused
      by baclofen was prevented by NEM, suggesting that GABA(B)Rs inhibit N-type
      channels via G-protein activation.

PMID- 17559100
TI  - Fiber connections of the diencephalic nucleus tuberis anterior in the weakly
      electric fish, Gymnotus cf. carapo: an in vivo tract-tracing study.
AB  - Transport of biotinylated dextran amine shows the spatial segregation of
      mechanosensory afferents in the nucleus tuberis anterior (TA) of a gymnotiform
      fish, Gymnotus cf. carapo. Only the intermediate subdivision of this nucleus
      receives projections from the lateral region of the ventral torus semicircularis
      (TSv), which represents the principal midbrain center for mechanosensory
      information processing, and from the ventral nucleus praeeminentialis, which
      receives collaterals of ascending second order mechanosensory fibers that emerge
      from the mechanosensory lateral line lobe. Considering this aspect, a
      rostrocaudal subdivision of the TA is proposed. The TA also receives input from
      regions subserving other sensory modalities, suggesting a role in multisensory
      interaction. Another important finding of this work consisted in the
      demonstration of reciprocal connections between the TA and the inferior lobe of
      the hypothalamus, which is known to receive gustatory, visual, and electrosensory
      input and is therefore considered a multisensory integration center involved in
      feeding and aggressive behavior. Furthermore, reciprocal connections between the
      TA and the preelectromotor central-posterior/prepacemaker complex may provide an
      access for the processed mechanosensory information to interact with the
      transient modulations of the electric organ discharge that accompany different
      behaviors.

PMID- 17559101
TI  - Orexin axons in the rat ventral tegmental area synapse infrequently onto dopamine
      and gamma-aminobutyric acid neurons.
AB  - Cells in the ventral tegmental area (VTA) facilitate motivated behaviors, and the
      activity of VTA neurons is regulated by dense projections from the lateral
      hypothalamic area (LHA). Orexin (Orx) neurons in the lateral and perifornical
      hypothalamus play important roles in arousal, feeding, and energy metabolism. Orx
      cells contribute substantially to the LHA projection to the rat midbrain.
      However, the morphological features of Orx fibers in the VTA and whether they
      synapse onto dopamine (DA) or gamma-aminobutyric acid (GABA) neurons have not yet
      been investigated. We utilized immunoperoxidase and immunogold-silver staining to
      examine the morphological features and synaptic incidence of Orx-labeled axons in
      the VTA. We then combined immunoperoxidase labeling for Orx with immunogold
      silver labeling for GABA or for tyrosine hydroxylase (TH) in DA neurons. Electron
      microscopic analysis revealed that most Orx-labeled axons in the VTA were passing
      fibers. The less common Orx varicosities were occasionally apposed to TH- or GABA
      labeled dendrites without synapsing. Only a small proportion of Orx-positive
      axons synapsed onto dendrites or soma. The synapses included both asymmetric and
      symmetric types and targeted TH- and GABA-labeled profiles with equal frequency.
      These findings suggest that most Orx fibers in the VTA are axons passing to
      caudal brainstem structures. However, Orx does mediate some direct synaptic
      influence on VTA DA and GABA neurons. Additional nonsynaptic effects are
      suggested by the presence of numerous dense-cored vesicles. These studies have
      important implications for understanding the mechanisms whereby Orx can alter
      behavior through regulating VTA DA and GABA cell activity.

PMID- 17559102
TI  - Epineurial compartments and their role in intraneural ganglion cyst propagation:
      an experimental study.
AB  - New patterns of intraneural ganglion cyst formation are emerging that have not
      previously been explained in current pathoanatomic terms. We believe there are
      three important elements underlying the appearance of these cysts: (a) an
      articular branch of the nerve that connects to a nearby synovial joint; (b)
      ejected synovial fluid following the path of least resistance along tissue
      planes; and (c) the additional effects of pressure and pressure fluxes. The
      dynamic nature of cyst formation has become clearly apparent to us in our
      clinical, operative and pathologic practice, but the precise mechanism underlying
      the process has not been critically studied. To test our hypothesis that a
      fibular (peroneal) or tibial intraneural cyst derived from the superior
      tibiofibular joint could ascend proximally into the sciatic nerve, expand within
      it and descend into terminal branches of this major nerve, we designed a series
      of simple, qualitative laboratory experiments in two cadavers (four specimens,
      six experiments). Injecting dye into the outer or "epifascicular" epineurium of
      the fibular and the tibial nerves we observed its ascent, cross over and descent
      patterns in three of three specimens as well as its cross over after an outer
      epineurial sciatic injection. In contrast, injecting dye into the inner or
      "interfascicular" epineurium led to its ascent within the tibial nerve and its
      division within the sciatic nerve in one specimen and lack of cross over in a
      sciatic nerve injection. Histologic cross-sections of the nerves at varying
      levels demonstrated a tract of disruption within the outer epineurium of the
      nerve injected and the nerve(s) into which the dye, after cross over, descended.
      Those specimens injected in the inner epineurium demonstrated dye within this
      tract but without disruption of or dye intrusion into the outer epineurium. In no
      case did the dye pass through the perineurial layers. Coupled with our
      observations in previous detailed studies, these anatomic findings provide proof
      of concept that sciatic cross over occurs due to the filling of its common
      epineurial sheath; furthermore, these findings, support the unifying articular
      theory, even in cases wherein patterns of intraneural ganglion cyst formation are
      unusual. Additional work is needed to be done to correlate these anatomic
      findings with magnetic resonance imaging and surgical pathology.

PMID- 17559103
TI  - The construction of multi-factor crossover designs in animal husbandry studies.
AB  - For ethical reasons it is important to try to obtain as much useful information
      as possible from an animal experiment whilst minimizing the number of animals
      used. Crossover designs, where applicable, provide an ideal framework for
      achieving this. If two or more treatment factors are included in the crossover
      design then the reduction in total animal usage can be considerable. In this
      paper we consider such designs, defined as multi-factor crossover designs. The
      designs are applicable when there are several different treatment factors, each
      at t levels, to be applied to the experimental units. The motivation for
      investigating these designs was a study conducted at GlaxoSmithKline to determine
      the preference of male and female dogs for t=5 different types of bed and t=5
      different bedding conditions. A construction method is given for forming
      universally optimal designs for t not too large. Also given is an example for the
      special case where the number of treatment levels t=6.

PMID- 17559104
TI  - Simulation of motoneuron morphology in three dimensions. I. Building individual
      dendritic trees.
AB  - We have developed a computational method that accurately reproduces the three
      dimensional (3D) morphology of individual dendritic trees of six cat alpha
      motoneurons. The first step was simulation of trees with straight branches based
      on the branch lengths and topology of actual trees. A second step introduced the
      meandering, or wandering, trajectories observed in natural dendritic branches
      into the straight-branch tree simulations. These two steps each required only two
      parameters, one extracted from the data on actual motoneuron dendrites and the
      other adjusted by comparing simulated and observed trees, using measurements that
      were independent of the model specifications (i.e., emergent properties). The
      results suggest that: 1) there is a somatofugal "tropism" (a bias introduced by
      the environment that affects the trajectory of dendritic branches) that tends to
      constrain the lateral expansion of alpha motoneuron dendrites; and 2) that most
      of the meandering of natural dendritic branches can be described by assuming that
      they are fractal objects with an average fractal dimension D of about 1.05. When
      analyzed in the same way, the dendrites of gamma motoneurons showed no evidence
      of a similar tropism, although they had the same fractal dimension of branch
      meandering.

PMID- 17559105
TI  - Simulation of motoneuron morphology in three dimensions. II. Building complete
      neurons.
AB  - By using dendrogram data from six adult cat alpha motoneurons, we have
      constructed computer simulations of these cells in three dimensions (3D) by
      "growing" their dendritic trees from stem branches that were oriented as in the
      original cells. Individual trees were simulated by using the algorithms and
      parameters discussed in the companion paper (Marks and Burke [2007] J. Comp.
      Neurol. 503:685-700). It was not possible to distinguish real from simulated
      motoneurons by visual inspection of 3D drawings. Simulated cells were compared
      quantitatively with their actual exemplars by using features that were measured
      in spherical shells at various radii centered on the soma. These included nearest
      neighbor distances (NNDs) between branches, the sizes and overlaps between the
      territories of individual dendrites measured as convex hulls (polygons that
      enclose all branches passing through a shell), and the sizes of circular zones
      that contained no branches. We also compared the 3D fractal dimensions and
      lacunarity (a measure of the 3D dispersion of branches) in actual cells and their
      simulations. The statistical properties of these quantitative measures were not
      significantly different, suggesting that the simulation algorithm was quite
      successful. However, there were three exceptions: 1) there were more NNDs at
      distances < 50 microm in simulated than in actual motoneurons; 2) average
      overlaps between the territories of different dendrites were almost twice as
      large in simulated compared with actual motoneurons; and 3) estimates of
      lacunarity were also larger in simulated cells. These exceptions suggest that
      dendritic branches in actual motoneurons tend to avoid one another. We discuss
      possible interpretations of these results.

PMID- 17559106
TI  - Synthesis of enantiopure 2-aryl-2-methoxypropionic acids and determination of
      their absolute configurations by X-ray crystallography.
AB  - Racemic 2-aryl-2-methoxypropionic acids were enantioresolved by the use of (S)-(
      )-phenylalaninol 4. For instance, racemic 2-methoxy-2-phenylpropionic acid (+/-)
      7 was condensed with phenylalaninol (S)-(-)-4 yielding a diastereomeric mixture
      of amides, which was easily separated by HPLC on silica gel affording the first
      eluted amide (-)-13a and the second-eluted amide (+)-13b: alpha = 3.19, Rs =
      3.49. The absolute configuration of amide (-)-13a was determined to be (R;S) by X
      ray crystallography by reference to the S configuration of the phenylalaninol
      moiety. Amide (R;S)-(-)-13a was converted to oxazoline (R;S)-(-)-14a, from which
      enantiopure 2-methoxy-2-phenylpropionic acid (R)-(-)-7 was recovered. Other 2
      aryl-2-methoxypropionic acids, (R)-(-)-8, (R)-(-)-9, (R)-(+)-10, (R)-(-)-11, and
      (R)-(-)-12, were similarly prepared in enantiopure forms with the use of
      phenylalaninol (S)-(-)-4, and their absolute configurations were clearly
      determined by X-ray crystallography or by chemical correlation.

PMID- 17559107
TI  - Emergence of homochirality in far-from-equilibrium systems: mechanisms and role
      in prebiotic chemistry.
AB  - Since the model proposed by Frank (Frank FC, Biochem Biophys Acta 1953;11:459
      463), several alternative models have been developed to explain how an asymmetric
      non-racemic steady state can be reached by a chirally symmetric chemical reactive
      system. This paper explains how a stable non-racemic regime can be obtained as a
      symmetry breaking occurring in a far-from-equilibrium reactive system initiated
      with an initial imbalance. Departing from the variations around the original
      Frank's model that are commonly described in the literature, i.e. open-flow
      systems of direct autocatalytic reactions, we discuss recent developments
      emphasizing both an active recycling of components and an autocatalytic network
      of simple reactions. We will present our APED model as the most natural
      realization of such thermodynamic openness and non-equilibrium, of recycling and
      of network autocatalysis, each of these in prebiotic conditions. The different
      experimental and theoretical models in the literature will be classified
      according to mechanism. The place and role of such self-structured networks
      responsible for the presence of homochirality in the primitive Earth will be
      detailed.

PMID- 17559108
TI  - Standardized evaluation and reporting of stent fractures in clinical trials of
      noncoronary devices.
AB  - OBJECTIVES: Define the prospective surveillance and reporting parameters for
      assessment of metallic stents used in clinical trials of superficial femoral
      artery atherosclerosis. BACKGROUND: While advances in medical therapies to
      improve atherosclerotic risk factor profiles in patients with peripheral arterial
      disease have focused on prevention of disease progression, the development of
      endovascular devices is altering the therapeutic algorithm for patients with
      peripheral arterial disease. Stents have emerged as one of the advances that may
      promote durable patency, particularly in the infrainguinal arteries. METHODS: The
      Zilver-PTX is a prospective multicenter randomized trial of bare metal versus
      drug-eluting nitinol stents for superficial femoral artery peripheral arterial
      disease. A predefined surveillance program is mandated in this trial. During the
      genesis of this program, it became clear that no single standard has existed to
      identify, classify, and report fractures of metallic stents placed in peripheral
      arteries. RESULTS: This report defines the key components of prospective stent
      fracture surveillance, including location of radiographic images obtained, types
      of radiographic equipment, methods of limb, and image intensifier positioning,
      intervals required for imaging, grading schemes for reporting, and methods of
      analyzing the images. CONCLUSIONS: As the proliferation of minimally invasive
      revascularization strategies continues, the stability of metallic endoprostheses
      is increasingly critical. Uniform surveillance of these devices for fracture and
      disarticulation is important in order to compare the relative merits of various
      stent-based devices in clinical trials.

PMID- 17559109
TI  - In vivo bone response to 3D periodic hydroxyapatite scaffolds assembled by direct
      ink writing.
AB  - The in vivo bone response of 3D periodic hydroxyapatite (HA) scaffolds is
      investigated. Two groups of HA scaffolds (11 mm diameter x 3.5 mm thick) are
      fabricated by direct-write assembly of a concentrated HA ink. The scaffolds
      consist of cylindrical rods periodically arranged into four quadrants with
      varying separation distances between rods. In the first group, HA rods (250
      microm in diameter) are patterned to create pore channels, whose areal dimensions
      are 250 x 250 microm(2) in quadrant 1, 250 x 500 microm(2) in quadrants 2 and 4,
      and 500 x 500 microm(2) in quadrant 3. In the second group, HA rods (400 microm
      in diameter) are patterned to create pore channels, whose areal dimensions of 500
      x 500 microm(2) in quadrant 1, 500 x 750 microm(2) in quadrants 2 and 4, and 750
      x 750 microm(2) in quadrant 3. Each group of scaffolds is partially densified by
      sintering at 1200 degrees C prior to being implanted bilaterally in trephine
      defects of skeletally mature New Zealand White rabbits. Their tissue response is
      evaluated at 8 and 16 weeks using micro-computed tomography, histology, and
      scanning electron microscopy. New trabecular bone is conducted rapidly and
      efficiently across substantial distances within these patterned 3D HA scaffolds.
      Our observations suggest that HA rods are first coated with a layer of new bone
      followed by subsequent scaffold infilling via outward and inward radial growth of
      the coated regions. Direct-write assembly of 3D periodic scaffolds composed of
      micro-porous HA rods arrayed to produce macro-pores that are size-matched to
      trabecular bone may represent an optimal strategy for bone repair and replacement
      structures.

PMID- 17559110
TI  - The primacy of octacalcium phosphate collagen composites in bone regeneration.
AB  - We have engineered a scaffold constructed of synthetic octacalcium phosphate
      (OCP) and porcine collagen sponge (OCP/Col), and reported that OCP/Col
      drastically enhanced bone regeneration. In this study, we investigated whether
      OCP/Col would enhance bone regeneration more than beta-tricalcium phosphate (beta
      TCP) collagen composite (beta-TCP/Col) or hydroxyapatite (HA) collagen composite
      (HA/Col). Discs of OCP/Col, beta-TCP/Col, or HA/Col were implanted into critical
      sized defects in rat crania and fixed at 4 or 12 weeks after implantation. The
      newly formed bone and the remaining granules of implants in the defect were
      determined by histomorphometrical analysis, and radiographic and histological
      examinations were performed. Statistical analysis showed that the newly formed
      bone by the implantation of OCP/Col was significantly more than that of beta
      TCP/Col or HA/Col. In contrast, the remaining granules in OCP/Col were
      significantly lower than those in beta-TCP/Col or HA/Col. Bone regeneration by
      OCP/Col was based on secured calcified collagen and bone nucleation by OCP,
      whereas bone regeneration by beta-TCP/Col or HA/Col was initiated by poorly
      calcified collagen and osteoconductivity by beta-TCP or HA. This study showed
      that the implantation of OCP/Col in a rat cranial defect enhanced more bone
      regeneration than beta-TCP/Col and HA/Col.

PMID- 17559111
TI  - Osteoblast differentiation in vitro and in vivo promoted by Osterix.
AB  - C3H10T1/2/Osx, a stably transfected cell line with Osterix (Osx), was produced
      and chondrocytic and osteoblastic differentiation were studied in vitro. Osx
      promoted osteoblastic lineage that was dexamethasone dependent. Furthermore, in
      vivo, Osx induced ectopic mineralization in a heterotopic mouse muscle model.
      Skeletogenesis involves a cascade of molecular activities sequentially performed
      by osteoblasts and chondroblasts. A transcriptional factor gene Osx appears to
      influence cell disposition toward the chondrocytic or osteoblastic phenotype and
      therefore may be an important signaling cue for bone formation. Understanding the
      molecular conditions involved with Osx promoted osteoblast differentiation will
      facilitate therapeutic applications of Osx. Consequently, the objective of this
      study was to investigate chondrocytic and osteoblastic phenotype differentiation
      using an Osx plasmid DNA exploiting both in vitro and in vivo methodologies. In
      vitro, a stably transfected C3H10T1/2/Osx cell line was established and promotion
      of either an osteoblast or chondroblast phenotype was performed by selectively
      introducing dexamethasone (dex) and assaying mRNA content and phenotype markers.
      In vivo, a mouse muscle model was used to determine heterotopic ossification
      using designated Osx plasmid DNA doses incorporated in a (50:50 Poly (D,L-lactide
      co-glycolide) (i.e., PLGA) 3D scaffold. Histological assessment was used to
      determine implant responses. Quantitative real-time polymerase chain reaction (q
      RT-PCR) showed a significant increase in mRNA expression of osteocalcin (Ocn),
      Runx2, osteonectin (On) and osteopontin (Op) (p < 0.05) in the C3H10T1/2/Osx
      cells compared to the empty vector transfected cell control. At day 21,
      mineralization was demonstrated in the cultures of C3H10T1/2/Osx exposed to dex,
      but neither in cultures lacking dex nor controls. In the absence of dex,
      C3H10T1/2/Osx cells revealed a significantly higher expression of Sox9 and
      Aggrecan (Agc). In vivo, 80 microg of Osx plasmid DNA induced heterotopic
      mineralization 4 weeks following implantation in a mouse muscle model and the
      effect was dependent on the Osx plasmid DNA dose delivered in the PLGA scaffold.
      Using a non-committed cell line (C3H10T1/2), cell differentiation to an
      osteoblast phenotype appears to be dependent upon an interaction between
      intracellular events initiated by the transcriptional factor Osx and the presence
      of dex. The in vivo findings suggest Osx may promote osteoblast
      differentiationand mineralization at a heterotopic site.

PMID- 17559113
TI  - Human monocyte adhesion onto RGD and PHSRN peptides delivered to the surface of a
      polycarbonate polyurethane using bioactive fluorinated surface modifiers.
AB  - Fluorinated oligomers, when blended into polyurethane, have been shown to migrate
      to the surface and generate an interface that minimizes protein denaturation and
      reduces cell activation. This type of surface modification can be achieved with
      ppm quantities of a bioactive fluorinated surface modifier (BFSM), enabling the
      introduction of bioactive agents onto a surface in one manufacturing step. In the
      current study, two BFSMs were synthesized with covalently conjugated RGD and
      PHSRN peptides near the fluorine terminal groups, and were shown to be surface
      active in polyurethane blends. CyQuant cell enumeration, scanning electron
      microscopy, and cell viability assays all indicated that the bioactive (and
      fluorinated) substrates supported enhanced monocyte interaction. The simplicity
      of the surface modification technique and the demonstrated ability of the peptide
      BFSMs to influence cell attachment and spreading indicate the potential benefits
      and practical value of the BFSM technology in tailoring surfaces for biomaterial
      applications. This was specifically highlighted for human blood monocytes, a key
      cell involved in the early stages of wound healing.

PMID- 17559114
TI  - Combination material delivery of dexamethasone and growth factor in hydrogel
      blended with hyaluronic acid constructs for neocartilage formation.
AB  - The aim of this study was to assess the efficacy of poly(NiPAAm-co-AAc) blended
      with hyaluronic acid (HA) as an injectable cell vehicle and a cell therapeutic
      agent in the form of a supporting matrix for the chondrogenic differentiation of
      rabbit chondrocytes. Specially, rabbit chondrocytes were embedded in blended
      hydrogels co-encapsulation with dexamethasone (Dex) and growth factors for
      enhancing the chondrogenic differentiation. Blended hydrogel constructs
      consisting of embedded cells co-encapsulating Dex and TGF beta-3 or unloaded Dex
      and sTGF beta-3 served as controls to assess the effects of Dex on chondrogenic
      differentiation. Hydrogel constructs consisting of embedded cells co
      encapsulating Dex and TGF beta-3 on chondrogenic differentiation. The hydrogel
      constructs were injected subcutaneously into the nude mice and monitored for 1,
      4, and 8 weeks after the injection. The level of the cartilage-associated ECM
      proteins was determined by immunohistochemical (collagen type II; specific marker
      for chondrogenic differentiation), Safranin-O, and Alcian blue (GAG) staining.
      Over the same time period, the glycosamingoglycan content per cell remained
      constant for all formulations, indicating that the dramatic increase in cell
      number for samples with Dex and TGF beta-3 loaded in hydrogel constructs was
      accompanied by maintenance of the cell phenotypes.

PMID- 17559115
TI  - Antibiotic multiresistance strictly associated with IS256 and ica genes in
      Staphylococcus epidermidis strains from implant orthopedic infections.
AB  - In this study the presence both of the ica genes, encoding for biofilm
      exopolysaccharide production, and the insertion sequence IS256, a mobile element
      frequently associated to transposons, was investigated in relationship with the
      prevalence of antibiotic resistance among Staphylococcus epidermidis strains. The
      investigation was conducted on 70 clinical isolates derived from orthopedic
      implant infections. Among the clinical isolates investigated a dramatic high
      level of association was found between the presence of ica genes as well as of
      IS256 and multiple-resistance to all the antibiotics tested (oxacillin,
      penicillin, gentamicin, erythromycin, clindamycin, chloramphenicol,
      sulfamethoxazole + trimethoprim, ciprofloxacin, vancomycin). Noteworthy, a
      striking full association between the presence of IS256 and resistance to
      gentamicin was found, being none of the IS256-negative strain resistant to this
      antibiotic. This association is probably because of the link of the corresponding
      aminoglycoside-resistance genes, and IS256, often co-existing within the same
      staphylococcal transposon. In conclusion, in orthopedics, the presence of ica
      genes and that of IS256 in S. epidermidis genome should both be considered as
      informative markers of clinically relevant strains equipped with greatest and
      broadest resistance potential to survive to medical treatments.

PMID- 17559116
TI  - Effect of acidic degradation products of poly(lactic-co-glycolic)acid on the
      apatite-forming ability of poly(lactic-co-glycolic)acid-siloxane nanohybrid
      material.
AB  - The effect of poly(lactic-co-glycolic) acid (PLGA) degradation products on the
      apatite-forming ability of a PLGA-siloxane nanohybrid material were investigated.
      Two PLGA copolymer compositions with low and high degradability were used in the
      experiment. The PLGA-siloxane nanohybrid materials were synthesized by end
      capping PLGA with acid end-groups using 3-isocyanatopropyl triethoxysilane
      following the sol-gel reaction with calcium nitrate tetrahydrate. Two nanohybrid
      materials that had different degradability were exposed to simulated body fluid
      (SBF) for 1-28 days at 36.5 degrees C. The low degradable PLGA hybrid showed
      apatite-forming ability within 3 days of incubation while the high degradable one
      did not within 28 days testing period. The results were explained in terms of the
      acidity of the PLGA degradation products, which could directly influence on the
      apatite dissolution.

PMID- 17559117
TI  - Heparin/chitosan nanoparticle carriers prepared by polyelectrolyte complexation.
AB  - In this study, novel nanoparticles were prepared by polyelectrolyte complexation
      between heparin and chitosan on simple and mild conditions. The size,
      polydispersity, zeta potential, and morphology of the nanoparticles were
      characterized. Entrapment studies of the nanoparticles were conducted using
      bovine serum albumin (BSA) as a model protein. Specifically, the effects of the
      pH value of chitosan solution, chitosan molecular weight (MW), chitosan
      concentration, heparin concentration, and BSA concentration on the nanoparticle
      size, the nanoparticle yield, and BSA entrapment were studied in detail. We found
      that, the size and the yield of the nanoparticles were affected by the above
      factors. The nanoparticle yield played a crucial role in BSA entrapment, namely,
      more nanoparticles could encapsulate more BSA. At length, suitably high pH value
      of chitosan solution, moderate chitosan MW, increasing both heparin concentration
      and chitosan concentration at an optimal concentration ratio favored more
      nanoparticles formed and consequently a higher BSA entrapment efficiency.

PMID- 17559118
TI  - The development of magnetic degradable DP-Bioglass for hyperthermia cancer
      therapy.
AB  - In this study, a novel magnetic degradable material was developed by adding Fe
      ions into DP-Bioglass (Na(2)O-CaO-P(2)O(5)-SiO(2)) as thermoseed for hyperthermia
      cancer therapy under an alternating magnetic field. We have investigated the
      properties of developed magnetic DP-Bioglass including morphology, chemical
      composition, and magnetism. The degradability was conducted by measuring the
      released concentrations of Na, Ca, Si, P, and Fe ions. The biocompatibility was
      analyzed by biological assays, and the functional hyperthermia effect to cancer
      cells was evaluated by in vitro cell culture test. In the results, the morphology
      of synthesized magnetic DP-Bioglass was revealed in sphere and rod shape with
      particle size around 50-100 nm. From the hysteresis loop analysis, it showed that
      the group of Fe/Bioglass = 0.2 possessed the maximum magnetization property. When
      cultured with fibroblasts, the magnetic DP-Bioglass had no significant influence
      on cell viability and mediated low cytotoxicity. The thermal-induced property
      demonstrated that after exposure to an alternating magnetic field, the cell
      number of human Caucasian lung carcinoma cells (A549) was significantly decreased
      when temperature was increasing to 45 degrees C. In brief, successfully
      incorporated with Fe ions by sol-gel method, this magnetic degradable DP-Bioglass
      possessed the potential and properties of hyperthermia effect to lung carcinoma
      cells.

PMID- 17559119
TI  - Automated analysis of FISH and immunohistochemistry images: a review.
AB  - Fluorescent in-situ hybridization (FISH) and immunohistochemistry (IHC)
      constitute a pair of complimentary techniques for detecting gene amplification
      and overexpression, respectively. The advantages of IHC include relatively cheap
      materials and high sample durability, while FISH is the more accurate and
      reproducible method. Evaluation of FISH and IHC images is still largely performed
      manually, with automated or semiautomated techniques increasing in popularity.
      Here, we provide a comprehensive review of a number of (semi-) automated FISH and
      IHC image processing systems, focusing on the algorithmic aspects of each
      technique. Our review verifies the increasingly important role of such methods in
      FISH and IHC; however, manual intervention is still necessary in order to resolve
      particularly challenging or ambiguous cases. In addition, large-scale validation
      is required in order for these systems to enter standard clinical practice.

PMID- 17559120
TI  - Tubular cationized pullulan hydrogels as local reservoirs for plasmid DNA.
AB  - In the present study, we measured the ability of various cationized pullulan
      tubular hydrogels to retain plasmid DNA, and tested the ability of retained
      plasmid DNA to transfect vascular smooth muscle cells (VSMCs). Cationized
      pullulans were obtained by grafting at different charge densities ethylamine (EA)
      or diethylaminoethylamine (DEAE) on the pullulan backbone. Polymers were
      characterized by elemental analysis, acid-base titration, size exclusion
      chromatography, Fourier-transform infrared spectroscopy, and proton nuclear
      magnetic resonance. The complexation of cationized pullulans in solution with
      plasmid DNA was evidenced by fluorescence quenching with PicoGreen. Cationized
      pullulans were then chemically crosslinked with phosphorus oxychloride to obtain
      tubular cationized pullulan hydrogels. Native pullulan tubes did not retain
      loaded plasmid DNA. In contrast, the ability of cationized pullulan tubes to
      retain plasmid DNA was dependent on both the amine content and the type of amine.
      The functional integrity of plasmid DNA in cationized pullulan tubes was
      demonstrated by in vitro transfection of VSMCs. Hence, cationized pullulan
      hydrogels can be designed as tubular structures with high affinity for plasmid
      DNA, which may provide new biomaterials to enhance the efficiency of local
      arterial gene transfer strategies.

PMID- 17559121
TI  - Influence of hydroxyl content on selected properties of 45S5 bioactive glass.
AB  - Numerous material properties may be influenced by the concentration of chemically
      dissolved hydroxyl species within a glass. A tube furnace connected to a steam
      generator was used to create hydroxyl-saturated 45S5 glass under 1 atm of water
      at 1100 degrees C. Selected properties of as-melted and hydroxyl-saturated
      samples were compared to assess the sensitivity of 45S5 to excess hydroxylation.
      The glass transition temperature and the peak crystallization temperature of the
      treated 45S5 glass were reduced in comparison to the as-melted 45S5 glass. In
      addition, the treated glass exhibited a broad endothermic signal that may be
      indicative of enhanced viscous flow. A simple dissolution experiment indicated
      that the treated 45S5 glass was also less durable than the as-melted 45S5 glass.

PMID- 17559122
TI  - STAT1 activation in squamous cell cancer of the oral cavity: a potential
      predictive marker of response to adjuvant chemotherapy.
AB  - BACKGROUND: For patients with squamous cell carcinoma of the oral cavity, both
      locoregional and distant recurrences are common, and an appropriate adjuvant
      treatment modality has yet to be defined. Thus, there is an urgent need to
      identify novel molecular markers with potential prognostic and/or predictive
      value to improve treatment outcome in these patients. This retrospective study
      was designed to investigate the predictive and/or prognostic value of STAT1
      activation in squamous cell carcinoma of the oral cavity. METHODS: STAT1
      expression and subcellular localization was examined immunohistochemically on a
      tissue microarray of paraffin-embedded tumor specimens from 89 patients who
      underwent surgical treatment in the period between 1980 and 1997. A nuclear
      staining score of greater than 35% was defined as high STAT1 activation. RESULTS:
      According to study criteria, 18% of analyzed tumor samples exhibited high STAT1
      activation. High STAT1 activation was associated with negative lymph node status.
      Moreover, in the subgroup of patients who received chemotherapy, high nuclear
      STAT1 staining in the tumor was associated with good prognosis. CONCLUSIONS: This
      is the first report demonstrating the potential predictive value of STAT1
      activation status in patients with squamous cell cancer of the oral cavity. If
      confirmed in large prospective trials, this molecular marker could help in
      guiding therapeutic decisions in these patients.

PMID- 17559123
TI  - Rates of myocardial infarction and coronary artery disease and risk factors in
      patients treated with radiation therapy for early-stage breast cancer.

PMID- 17559125
TI  - The response of osteoblast-like cells towards collagen type I coating immobilized
      by p-nitrophenylchloroformate to titanium.
AB  - The scaffold surface composition can be altered by the use of surface coatings.
      The use of thin coatings will give special surface properties, while the bulk
      properties of the scaffold are preserved. Collagen type I is known to play an
      important role during cell adhesion as well as osteoblast differentiation. A
      common way to coat surfaces is the adsorption method. An alternative way is the
      use of a protein immobilization method like p-nitrophenyl chloroformate. In this
      study, we investigated the effect of a collagen type I coating and p-nitrophenyl
      chloroformate as a protein immobilization method on osteoblast adhesion,
      proliferation, and differentiation. Titanium fiber meshes were treated with
      sodium hydroxide (NaOH), followed by p-nitrophenyl chloroformate, and coated with
      collagen type I. Osteoblast-like cells were seeded into the meshes and cultured
      for 24 days. The cell attachment, proliferation, and differentiation were
      measured by using Live and Dead assay, cell counting, DNA analysis, alkaline
      phosphatase activity assay, calcium content measurement, Real Time PCR (QPCR),
      and scanning electron microscopy (SEM). Results demonstrated that initially less
      cells were attached to the covalently bounded collagen meshes (NPC-Col) compared
      with titanium as control (Ti) and adsorbed collagen meshes (ABS-Col). Further, a
      decreased growth curve of cells cultured on the NPC-Col meshes was observed in
      comparison with Ti and ABS-Col meshes. The calcium measurements and SEM pictures
      revealed that all three surfaces showed differentiation of osteoblast-like cells
      after 8-24 days. On the basis of our results, we conclude that initially less
      cells were attached to the NPC-Col meshes and that they had a decreased
      proliferation rate. Further, we conclude that an adsorbed collagen type I coating
      stimulated the osteoblastic differentiation of rat bone marrow cells.

PMID- 17559126
TI  - X-ray repair cross-complementing group 1 (XRCC1) single-nucleotide polymorphisms
      and the risk of salivary gland carcinomas.
AB  - BACKGROUND: X-ray repair cross complementing group 1 (XRCC1) is important in the
      repair of single-strand DNA breaks caused by endogenous oxidative species and
      exogenous carcinogens. METHODS: This tertiary cancer center-based, case-control
      association study included 138 patients with salivary gland carcinoma (SGC), 50
      patients with benign salivary gland tumors, and a group of 503 cancer-free
      control participants. Polymerase chain reaction-restriction fragment length
      polymorphism genotyping assays were performed on 6 XRCC1 single-nucleotide
      polymorphisms (SNPs). Odds ratios (ORs) and 95% confidence intervals (95% CIs)
      were calculated in multivariate logistic regression analyses, and haplotype
      distributions were estimated. RESULTS: The XRCC1 genotype distributions of
      patients with SGC and control participants differed significantly for both the
      T1915C promoter SNP (P = .047) and the Arg194Trp coding region SNP (P = .037).
      The polymorphic 1915C allele was significantly less frequent in patients with SGC
      than in the controls (34% vs 42%; P = .031). Multivariate analysis demonstrated
      that individuals who had the 1915 polymorphic homozygous CC genotype (OR, 0.4;
      95% CI, 0.2-0.9; P = .017) had a significantly lower risk of SGC, and individuals
      who had the Arg194Trp heterozygous CT genotype (OR, 1.6; 95% CI, 1.0-2.6; P =
      .059) had a higher, borderline significant risk. The CGTTGG haplotype was
      associated with a higher SGC risk (OR, 3.5; 95% CI, 1.1-11.3; P = .036). No
      findings were significant for the patients who had benign salivary gland tumors.
      CONCLUSIONS: In this study, the XRCC1 1915C allele was associated with a lower
      SGC risk, and the XRCC1 194Trp allele was associated with a higher SGC risk.

PMID- 17559127
TI  - Structure, depolymerization, and cytocompatibility evaluation of glycol chitosan.
AB  - Glycol chitosan, a water soluble chitosan derivative being investigated as a new
      biomaterial, was fractionated via two different methods. Initial characterization
      of the glycol chitosan with (1)H NMR spectroscopy illustrated the presence of
      both secondary and tertiary amine groups, contradictory to its widely accepted
      structure. Fractionation of glycol chitosan with nitrous acid resulted in a
      significant reduction in the number average molecular weight, specifically, from
      170 to approximately 7 kDa for a pH 3 and below. However, the reaction altered
      its chemical structure, as the secondary amine groups were converted to N
      nitrosamines, which are potentially carcinogenic. An increase in the pH of the
      reaction limited this formation, but not entirely. Free radical degradation
      initiated with potassium persulfate was not as effective at reducing the
      molecular weight as the nitrous acid approach, yielding molecular weights around
      12 kDa under the same molar ratio of degrading species, but did retain the
      structural integrity of the glycol chitosan. Additionally, control of the
      molecular weight appears feasible with potassium persulfate. When assessed in
      vitro for cytocompatibility, the polymer exhibited no toxicity on monolayer
      cultured chondrocytes, and in fact stimulated cell growth at low concentrations.

PMID- 17559128
TI  - Quick-forming hydroxyapatite/agarose gel composites induce bone regeneration.
AB  - We investigated the fundamental properties of quick-forming hydroxyapatite
      (HAp)/agarose gel composites, and evaluated their potential as an injectable bone
      substitute. From scanning electron microscope observations, the HAp/agarose gel
      composites produced by an innovative electrophoretic process showed an
      interconnecting structure with the HAp particles. The diameter of the HAp
      particles was roughly 1 microm, and the total amount of HAp particles was
      estimated by a quantification of the calcium ions. In the case of 1 mg of dry
      composite, 10 microg of HAp was formed in the agarose gel. Moreover, X-ray
      diffraction analysis revealed that the HAp particles had an amorphous structure,
      so the HAp particles were expected to dissolve under physiological conditions
      relative to the HAp with higher crystallinity. The advantages of the resultant
      HAp/agarose gel composites are ease of handling, close contact with the
      surrounding tissues, and ease of use as an injectable material. As a preliminary
      animal study, the composites were implanted into the medial femoral condyle of
      rabbits. After implantation, the process of bone regeneration was evaluated by
      microfocus-computed tomography (microCT) and histological analysis. At 2 weeks
      postoperatively, newly-formed bone was observed at the edge of the bone defect
      site, and at 4 weeks postoperatively, excellent bone regeneration was observed.
      The implanted composite gradually degraded, and disappeared at 8 weeks
      postoperatively. This result indicated that the composite dissolved rapidly, and
      was replaced by newly-formed bone. Quick-forming HAp/agarose gel composites may
      be a good candidate as an injectable biomaterial, particularly in the fields of
      orthopedic, oral, and maxillofacial surgery.

PMID- 17559129
TI  - Antimicrobial polyethylene with controlled copper release.
AB  - Good antiinfection properties of medical polymers, especially those used in
      artificial organs, are crucial to the minimization of microbial attack in
      nosocomial treatments. However, medical polymers fabricated by conventional
      methods usually have unstable and short-lived antimicrobial effects because of
      unsteady out-diffusion of the antibacterial species from the organic matrix.
      Here, we introduce a dual plasma implantation process to enhance the properties.
      An inorganic antibacterial element, copper, is introduced into a medical polymer,
      polyethylene (PE), by means of copper plasma immersion ion implantation (PIII)
      and a subsequent nitrogen PIII process is used to regulate the release of the
      implanted Cu. X-ray photoelectron spectroscopy and transmission electron
      microscopy reveal that a relatively large amount of copper of about 11% is
      implanted into PE to a depth of several hundred nanometers. Chemical analyses
      confirm that the implanted Cu does not bond with the polymer matrix. However, the
      N(2) plasma treatment produces various functional bonds such as C=N, and C[triple
      bond]N which exert appreciable influence on regulating the out-diffusion rate of
      copper. The large amount of embedded Cu, coupled with controlled release of the
      element to the surface, gives rise to excellent and long-lasting surface
      antibacterial properties of the plasma-treated polymer. The capability of
      controlling the release and storing the antibacterial reagent in a buried layer
      leads to better antimicrobial polymeric materials for medicine.

PMID- 17559130
TI  - Metal oxide coated cell culture arrays for rapid biological screening.
AB  - The biointerface of metallic alloy implants is a spontaneously formed metal oxide
      layer. This study presents a novel method for creating titanium oxide xerogel
      coated microplates for high-throughput biological screening that overcomes
      several limitations of using bulk metal samples to study oxides. Metal-organic
      precursors were used to evaluate the influence of Al, V, Ca, and P doped smooth
      and textured titanium oxide xerogel coatings on the bioresponse of human
      fibroblasts to increase understanding of the soft tissue sealing around
      transepithelial devices. Coatings made of titanium n-butoxide were
      characteristically smooth, while those of titanium isopropoxide were micro- and
      nanofeatured. Screening consisted of WST-1 proliferation assay, calcein AM cell
      number and viability assay, and a modified cell seeding efficiency and
      centrifugation adhesion assay. Small variations in initial attachment and
      centrifugation adhesion of human fibroblasts were observed among the coatings and
      comparable to tissue-culture treated polystyrene. Proliferation and viability at
      24 and 48 h were reduced by the 10 and 20% vanadium additions. Metal oxide coated
      microplates are adaptable to the investigation of a wide range of metal-organic
      derived chemistries and the influence of oxide texture, and level of oxide
      crystallinity and oxide grain size on the biological responses of cells.

PMID- 17559131
TI  - Locally advanced prostate cancer: biochemical results from a prospective phase II
      study of intermittent androgen suppression for men with evidence of prostate
      specific antigen recurrence after radiotherapy.

PMID- 17559132
TI  - Hydrogen bonding interactions in methacrylate monomers and polymers.
AB  - It is well appreciated that hydrogen bonding affects a variety of monomer and
      polymer properties. This study focused on Bis-GMA and urethane dimethacrylate
      (UDMA) to help elucidate how the strength and nature of specific noncovalent
      interactions involved with these different functional dimethacrylate structures
      are expressed in the monomers and polymers. Hydrogen bonding interactions in
      monomers and comonomer mixtures as well as in appropriate model compounds were
      examined by FT-IR under ambient conditions, at elevated temperatures and in
      dilution studies. The investigation of hydrogen bonding extended to monomer
      viscosity, photopolymerization reaction kinetics, and polymer mechanical
      properties. The strength of hydrogen bonding was shown not only to be greater for
      Bis-GMA compared with UDMA, but there is also greater contribution from
      intermolecular interactions that enhance the hydrogen bonding effects. While UDMA
      based polymers reach significantly higher levels of conversion compared with Bis
      GMA materials, the stronger hydrogen bonding reinforcement associated with Bis
      GMA appears to provide for comparable mechanical strength properties. Depending
      on the hydrogen bond donor functionality of a monomer as well as its neighboring
      functional groups, overall monomer structure and comonomers used, hydrogen
      bonding can favorably affect polymerization reactivity and mechanical properties,
      even in materials that form highly crosslinked polymeric networks.

PMID- 17559133
TI  - Broadening cell selection criteria with micropallet arrays of adherent cells.
AB  - A host of technologies exists for the separation of living, nonadherent cells,
      with separation decisions typically based on fluorescence or immunolabeling of
      cells. Methods to separate adherent cells as well as to broaden the range of
      possible sorting criteria would be of high value and complementary to existing
      strategies. Cells were cultured on arrays of releasable pallets. The arrays were
      screened and individual cell(s)/pallets were released and collected. Conventional
      fluorescence and immunolabeling of cells were compatible with the pallet arrays,
      as were separations based on gene expression. By varying the size of the pallet
      and the number of cells cultured on the array, single cells or clonal colonies of
      cells were isolated from a heterogeneous population. Since cells remained
      adherent throughout the isolation process, separations based on morphologic
      characteristics, for example cell shape, were feasible. Repeated measurements of
      each cell in an array were performed permitting the selection of cells based on
      their temporal behavior, e.g. growth rate. The pallet array system provides the
      flexibility to select and collect adherent cells based on phenotypic and temporal
      criteria and other characteristics not accessible by alternative methods.

PMID- 17559134
TI  - Real-time fluorescence detection of multiple microscale cell culture analog
      devices in situ.
AB  - We investigated multiple microscale cell culture analog (microCCA) assays in situ
      with a high-throughput imaging system that provides quantitative, nondestructive,
      and real-time data on cell viability. Since samples do not move between
      measurements, captured images allow accurate time-course measurements of cell
      population response and tracking the fate of each cell type on a quantitative
      basis. The optical system was evaluated by measuring the short-term response to
      ethanol exposure and long-term growth of drug-resistant tumor cell lines with
      simultaneous samples. The optical system based on epi-fluorescent excitation
      consists of an LED and a CCD as well as discrete optical components for imaging a
      large number of cells simultaneously. HepG2/C3A and MESSA cell lines were
      cultured in two microCCA systems for continuous cell status monitoring in cell
      death experiments with ethanol and long-term cell growth. The experiment that
      tested ethanol uptake showed that ethanol immediately caused cell death. The
      system was applied to extracting dynamic constants in the uptake process. In the
      long-term cell growth experiment, growth of MESSA cells was followed by a
      stationary phase and eventual cell death attributed to nutrient and oxygen
      depletion and a change in the pH because of the accumulation of wastes by cell
      metabolism. HepG2/C3A cells were subject to contact inhibition and cell number
      did not change significantly over time. Issues related to long-term assays are
      also discussed. The quantitative results have been consistent with qualitative
      images and confirm the applicability of the portable optical system, and
      potential application to high-throughput analysis of cell-based assays to measure
      long-term dynamics.

PMID- 17559135
TI  - The role of noncartilage-specific molecules in differentiation of cartilaginous
      tumors: lessons from chondroblastoma and chondromyxoid fibroma.
AB  - BACKGROUND: Chondroblastoma (CB) and chondromyxoid fibroma (CMF) are benign
      tumors of bone morphologically recapitulating cartilage differentiation. CMF can
      resemble high-grade central chondrosarcoma (HGCCS) because of its cellular
      atypia. The mechanism that drives this morphologic spectrum of cartilage
      differentiation is unclear. METHODS: CMFs and CBs were hybridized on a
      complementary DNA microarray that was enriched for cartilage-specific genes. Data
      were analyzed by Linear Model for Microarray Analysis and were compared with
      previous data on osteochondromas and HGCCS. Verification was performed in an
      extended series. RESULTS: None of the 68 genes that were differentially expressed
      in CB versus CMF, including several extracellular matrix (ECM) and ECM
      degradation genes, were related specifically to cartilage. Perlecan, versican,
      collagen 4A2 (Col4A2), and cell-cell adhesion genes, such as CD166, were
      significantly higher in CMF. Sixty genes were expressed differentially in CMF
      versus HGCCS. Higher expression levels of CD166, cyclin D1 (CCND1), and p16INK4A
      were observed in CMF. CONCLUSIONS: The current findings indicated that
      differential expression of adhesion and ECM molecules, such as CD166, versican,
      perlecan, and Col4A2, may interfere with cartilaginous differentiation. The
      decreased expression of CCND1, p16INK4A, and CD166 in HGCCS reflects impairment
      of cell cycle progression and of cell-cell adhesions in malignant tumors and is
      of use in the differential diagnosis of CMF.

PMID- 17559136
TI  - Racial disparities in blacks with gynecologic cancers.
AB  - Black women have a lower incidence of gynecologic cancers but they have a higher
      mortality associated with their disease. The etiology of the racial disparity in
      outcome among gynecologic cancer patients is multifactoral and site-specific.
      Black women with endometrial cancer often present with more advanced stage tumors
      that are associated with a worse prognosis compared with White women. Evidence
      suggests that observed disparities in outcome are due to inequalities in
      treatment or differing biologic etiologies. For cervix cancer, studies have
      suggested that survival among Black women may be lower than survival among White
      women that develop this disease. This occurs despite evidence that indicates that
      Pap smears are utilized similarly by Black and White women for cervix cancer
      screening. These differences in outcome may become less pronounced when
      comorbidities are accounted for and inequalities in treatment are eliminated. For
      ovarian cancer patients, survival has improved with the use of contemporary
      therapies over the past 30 years in Whites but less so for Blacks. This may be
      due to differences in the likelihood of primary surgical cytoreductions, which
      are performed less frequently in some Black women because of extensive metastatic
      spread or comorbidities. The observed decreases in survival for all 3 gynecologic
      cancers potentially may be affected by socioeconomic status of the patient in
      some healthcare settings. An improved understanding of the causative factors
      associated with racial disparities in gynecologic cancer outcome is necessary to
      facilitate efforts aimed at correcting this important healthcare problem.

PMID- 17559137
TI  - Parathyroid carcinoma, atypical parathyroid adenoma, or parathyromatosis?
AB  - BACKGROUND: Parathyroid carcinoma, atypical parathyroid adenoma, and
      parathyromatosis can be differentiated relatively easily from typical parathyroid
      adenomas, but distinguishing them from each other is more difficult. METHODS: A
      retrospective study of 28 consecutive patients with parathyroid carcinoma, 7
      patients with atypical parathyroid adenoma, and 13 patients with parathyromatosis
      who were treated at the University of California at San Francisco Medical Center
      between 1966 and 2005 was performed. Patient demographics and clinical
      characteristics, indication for surgery, intraoperative findings, histopathologic
      characteristics, disease recurrence or persistence, site of invasion/metastases,
      and survival were compared in the 3 groups. RESULTS: Parathyroid carcinoma (19 of
      28 patients) and atypical adenoma (4 of 7 patients) were significantly more
      common in men, whereas parathyromatosis was more common in women (10 of 13
      patients) (P = .02). A palpable neck mass and hoarseness were almost exclusively
      present in patients with parathyroid carcinoma. Prior to the first parathyroid
      surgery, patients with parathyroid carcinoma were found to have higher blood
      calcium levels (>/=14 mg/dL in 16 of 26 patients [62%]), whereas only 1 of 6
      patients with atypical adenoma (17%) and no patients with parathyromatosis were
      found to have profound hypercalcemia (P < .01). Intraoperatively, patients with
      parathyroid carcinoma and atypical adenoma presented with single lesions, whereas
      patients with parathyromatosis had multiple small lesions. Histopathologic
      findings were well defined in parathyroid carcinoma, but some findings overlapped
      in the 3 tumors studied. CONCLUSIONS: Patients with parathyroid carcinoma often
      differ from those with atypical parathyroid adenoma or parathyromatosis at the
      time of presentation because patients with parathyroid carcinoma have more
      profound hypercalcemia as well as invasive tumors. However, at times it is
      difficult to distinguish between these conditions both clinically and by final
      histologic examination.

PMID- 17559138
TI  - Correlates of screening sigmoidoscopy use among men in a large nonprofit health
      plan.
AB  - BACKGROUND: As the majority of patients diagnosed with colorectal cancer have no
      known risk factors, regular screening is strongly recommended. The authors
      examined factors associated with screening sigmoidoscopy use among participants
      in the California Men's Health Study (CMHS). METHODS: The authors conducted a
      cross-sectional study over a 5-year period nested within a prospective cohort
      study. The CMHS enrolled a large multiethnic cohort (n = 84,170) of men from 2
      major California health plans. Because screening sigmoidoscopy was the preferred
      and most commonly used test for patients at average risk of colorectal cancer in
      the health plans, the authors excluded from the analysis men who completed a
      barium enema colonoscopy or a fecal occult blood test. RESULTS: Eligible subjects
      included 39,559 men at average risk for colorectal cancer. Prevalence of
      screening sigmoidoscopy use decreased with older age and increased with higher
      education and household income over the 5-year study period. Compared with
      whites, Asians (adjusted OR, 1.42; 95% CI, 1.30-1.56) and African Americans
      (adjusted OR, 1.18; 95% CI, 1.08-1.29) were more likely to undergo screening
      sigmoidoscopy. Screening increased with the number of outpatient visits and with
      having a primary care provider in internal medicine. Men who did not undergo
      prostate-specific antigen testing were also less likely to undergo sigmoidoscopy
      screening. Only 24.5% of current smokers had a screening sigmoidoscopy
      examination and were 25% less likely to undergo this procedure compared with
      nonsmokers (adjusted OR, 0.75; 95% CI, 0.69-0.82). CONCLUSIONS: In this insured
      population for whom financial barriers are minimized, screening sigmoidoscopy use
      was as low as reported in the general population. However, minority patients were
      not less likely to be screened.

PMID- 17559139
TI  - A prospective analysis of imatinib-induced c-KIT modulation in ovarian cancer: a
      phase II clinical study with proteomic profiling.
AB  - BACKGROUND: c-Kit and platelet-derived growth factor receptor (PDGFR) are
      potential molecular targets in epithelial ovarian cancer (EOC). Imatinib inhibits
      the kinase domain and subsequent downstream signaling of these receptor tyrosine
      kinases. The objective of this study was to investigate biochemical and biologic
      effects of imatinib on EOC. METHODS: Patients with recurrent EOC who had received
      no more than 4 prior regimens and who had good end-organ function were eligible.
      Imatinib was administered orally at a dose of 400 mg twice daily in continuous,
      28-day cycles with reassessment imaging studies obtained every other cycle. Tumor
      core biopsies were obtained prior to and at 4 weeks into therapy; microdissected
      tumor and stroma were subjected to protein lysate array analysis. Blood samples
      were obtained monthly for cytokine measurements. RESULTS: Twenty-three patients
      were enrolled, including 16 patients who received imatinib 600 mg daily because
      of gastrointestinal (GI) toxicity and fluid accumulation at the starting dose.
      The median time to disease progression was 2 months (range, 2-14 months). Common
      grade 3 toxicities included edema/ascites/pleural effusions in 11 patients (48%),
      GI complaints in 8 patients (35%), fatigue in 3 patients (13%), and grade 2 and 3
      cytopenias in 10 patients and 3 patients (43% and 13%), respectively. Increased
      circulating levels of interleukin 6 were associated with grade >/=2 fluid
      collection (P = .02). A statistically significant trend was observed between
      pretreatment phosphorylated-kit levels in microdissected tumor and stroma and GI
      toxicity (P < .01), between tumor levels of epidermal growth factor receptor
      (EGFR) and PDGFR with grade of fatigue (P </= .005), and EGFR and phosphorylated
      AKT levels with grade of ascites and edema (P </= .01). CONCLUSIONS: The results
      of this study indicated imatinib had minimal activity as a single agent in EOC.
      Its ability to modulate its molecular targets suggests that it may be considered
      in combinatorial therapy.

PMID- 17559140
TI  - Novel tyrosine kinase inhibitor therapy before allogeneic stem cell
      transplantation in patients with chronic myeloid leukemia: no evidence for
      increased transplant-related toxicity.
AB  - BACKGROUND: Patients undergoing allogeneic hematopoietic stem cell
      transplantation (HSCT) for chronic myeloid leukemia (CML) are increasingly likely
      to have received a novel tyrosine kinase inhibitor (NTKI) after failing imatinib
      mesylate. It is unknown whether the use of these NTKIs before HSCT increases
      transplant-related toxicity. METHODS: The outcome of 12 patients with CML (1 in
      chronic phase, 6 in the accelerated phase, and 5 in the blastic phase) who
      received dasatinib (n = 2), nilotinib (n = 7), or both (n = 3) before HSCT were
      retrospectively analyzed. RESULTS: The median time on treatment was 134 days, and
      the median time from the end of NTKI therapy to HSCT was 34 days. The preparative
      regimen was ablative in 8 patients and nonablative in 4. All patients engrafted
      within 13 days. There was no significant early transplant-related toxicity. One
      patient developed secondary graft failure after 6 months from the first HSCT that
      required a second HSCT. Acute and chronic graft-versus-host disease (GVHD) was
      observed in 7 and 6 patients, respectively. Nine patients achieved a molecular
      response: 4 complete and 5 major (quantitative reverse transcriptase-polymerase
      chain reaction <0.05%). Three patients had disease progression by Day 30 after
      HSCT. Two patients developed disease recurrence after a median of 12 months.
      After a median follow-up of 10 months, 7 patients were alive in molecular
      response and 5 patients had died, 4 of disease progression and 1 of extensive
      chronic GVHD. CONCLUSIONS: Previous treatment with NTKI did not increase
      transplant-related toxicity in this preliminary experience. Further follow-up and
      a larger number of patients will be necessary to confirm these observations.

PMID- 17559141
TI  - Intensive chemotherapy is not recommended for patients aged >60 years who have
      myelodysplastic syndromes or acute myeloid leukemia with high-risk karyotypes.
AB  - BACKGROUND: It is unclear whether intensive chemotherapy is beneficial to
      patients with high-risk myelodysplastic syndrome (MDS) or acute myeloid leukemia
      (AML) if they are aged >/=60 years. METHODS: The authors studied 160 patients
      with a median age of 67 years who received intensive chemotherapy for MDS or AML
      with cytosine arabinoside and an anthracycline. RESULTS: At diagnosis,
      cytogenetic analysis was available in 146 patients. Karyotype was normal in 78
      patients and abnormal in 68 patients. Of the abnormal karyotypes, 32 belonged to
      the high-risk category, ie, they involved either >/=3 chromosomes or chromosome
      7. Complete remission (CR) was achieved by 94 patients (56%). CR rates were 70%
      among the patients who had a normal karyotype, 69% among the patients who had an
      abnormal (noncomplex) karyotype, but only 46% among the patients ho had a high
      risk karyotype. The median survival was 9.5 months in the entire group, 18 months
      in patients with normal karyotype, 6 months in patients with abnormal, and 4
      months in patients with a high-risk karyotype. A poor prognosis was attributable
      to low rates of CR and a high risk of early recurrence. CONCLUSIONS: According to
      the current data, elderly patients with AML or advanced MDS do not benefit from
      intensive chemotherapy if they show karyotype anomalies, especially those in the
      high-risk category.

PMID- 17559142
TI  - Susceptibility to lung cancer and genetic polymorphisms in the alcohol metabolite
      related enzymes alcohol dehydrogenase 3, aldehyde dehydrogenase 2, and cytochrome
      P450 2E1 in the Japanese population.
AB  - BACKGROUND: It is believed that acetaldehyde plays an important role in alcohol
      related carcinogenesis; although current epidemiologic studies have provided
      inconsistent findings on the association between alcohol consumption and the risk
      of lung cancer. METHODS: To clarify the hypothesis that genetic polymorphisms in
      alcohol-metabolizing enzymes may influence susceptibility to lung cancer, the
      authors conducted a hospital-based case-control study and examined genetic
      polymorphisms in the alcohol dehydrogenase 3, aldehyde dehydrogenase 2 (ALDH(2)),
      and cytochrome P450 2E1 genes in 505 patients with histologically confirmed lung
      cancer and in a group of 256 noncancer controls who provided complete cigarette
      and alcohol consumption histories. Genotyping was conducted by polymerase chain
      reaction-restriction fragment-length polymorphism assay. RESULTS: A significant
      association was noted between alcohol consumption and lung cancer risk. Thus,
      using the median value for the controls as the cut-off point, the odds ratios
      (OR) for light and heavy drinkers were 1.76 and 1.95, respectively (P for trend =
      .012), compared with nondrinkers. In addition, there was a significant trend
      toward increased risk of lung cancer in drinkers with ALDH(2) variant alleles (P
      for trend <.0001). The adjusted OR for heavy drinkers was 6.15 compared with
      nondrinkers. Regarding associations between histologic type and genotypes, the
      ALDH(2) variant allele was significantly less common in patients who had
      adenocarcinoma compared with controls. CONCLUSIONS: The current observations
      suggested a positive association between alcohol consumption and the risk of lung
      cancer: Drinking may increase the risk, especially among individuals who have the
      variant ALDH(2) alleles.

PMID- 17559143
TI  - Induction of epithelial-mesenchymal transition-related genes by benzo[a]pyrene in
      lung cancer cells.
AB  - BACKGROUND: It is believed that epithelial-mesenchymal transition (EMT) occurs
      during the development and progression of cancer; however, the correlation
      between tobacco smoking and EMT remains to be elucidated. METHODS: Cells from the
      bronchioloalveolar carcinoma cell line A549 were exposed to benzo(a)pyrene
      (B[a]P) for 24 weeks, and morphology, proliferative activity, and gene expression
      profiles were analyzed. RESULTS: Although no apparent morphologic changes were
      observed, the B[a]P-exposed A549 cells exhibited enhanced proliferative activity
      in 1% bovine serum that contained medium, and dramatic changes in expression
      levels were observed in a large number of genes. Of those, the expression of EMT
      related genes, such as migration-stimulating factor, plasminogen activator
      inhibitor-1, fibronectin, twist, transforming growth factor-beta2, basic
      fibroblast growth factor, and electron transport system, were up-regulated;
      whereas gene expression of E-cadherin was decreased. Most enhanced expression
      levels remained 8 weeks after the retrieval of B[a]P in culture. CONCLUSIONS: The
      current results indicated that B[a]P seems to induce EMT in lung cancer cells,
      and it also may drive disease progression in patients with lung cancer.

PMID- 17559144
TI  - Generation and characterization of an ascitogenic mesothelin-expressing tumor
      model.
AB  - BACKGROUND: Intraperitoneal tumors expressing high amounts of mesothelin such as
      malignant mesothelioma and ovarian cancers tend to develop ascites and result in
      significant morbidity and mortality in the patient. A suitable preclinical
      intraperitoneal model will assist in the illustration of the mechanisms of
      molecular oncogenesis and facilitate in addressing issues related to early
      screening, diagnosis, and therapy for intraperitoneal tumors. METHODS: In the
      current study, an ascitogenic malignant tumor model (WF-3) was created. The
      mobility and proliferation of WF-3 and its precursor cells, WF-0, were
      characterized using transwell and MTT (3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide) assays. In addition, the in vivo tumorgenicity of WF
      3 and WF-0 was determined using intraperitoneal injection of the tumor cells.
      Microarray analysis was performed using WF-3 and WF-0. Northern blot analysis was
      used to characterize the expression of the mesothelin gene in WF-3 and WF-0.
      Furthermore, the mesothelin levels in serum and ascites were used to correlate
      with tumor load of WF-3 in tumor challenged mice. RESULTS: The WF-3 tumor cells
      demonstrated relatively high proliferation and migration rates compared with the
      parental cell line, WF-0. The tumors from the WF-3 but not WF-0 were capable of
      forming ascites and peritoneal-based tumors after tumor challenge. The WF-3 tumor
      model was also capable of implanting into multiple organs including the
      diaphragm, intestines, and peritoneal wall. Furthermore, the WF-3 tumor expressed
      high levels of mesothelin, which is commonly observed in the majority of ovarian
      cancers, pancreatic cancer, and malignant mesothelioma. In addition, the authors
      found that the serum and ascites mesothelin levels correlated with tumor loads in
      tumor-challenged mice. CONCLUSIONS: The data indicate that the WF-3 murine tumor
      model may potentially serve as a good model for understanding the molecular
      oncogenesis of peritoneal tumors. In addition, the preclinical model may
      potentially be useful for the development of diagnostic and therapeutic methods
      against intraperitoneal cancers.

PMID- 17559145
TI  - Trop-1 are conserved growth stimulatory molecules that mark early stages of tumor
      progression.
AB  - BACKGROUND: Trop-1 is a cell-cell adhesion regulatory molecule that is
      overexpressed by a large fraction of tumors in man. METHODS: To identify
      fundamental, conserved functional features of Trop-1 in transformed cells, a
      search was performed for evolutionarily conserved structure, expression patterns,
      and function by gene cloning, DNA array and serial analysis of gene expression
      (SAGE), Northern and Western blotting, flow cytometry, and immunohistochemistry
      of sequential stages of tumor progression in experimental systems and in man.
      RESULTS: TROP1 genes demonstrate conserved structure and promoter regions with
      parallel expression patterns (high expression in the small intestine and colon;
      lower expression in prostate, thyroid, salivary glands, breast, kidney, lung,
      liver, and spleen; very low levels in skin and stomach; no expression in heart,
      muscle, and brain). Progenitor cells of different tissues were shown to express
      Trop-1. Hence, the expression and functional role of Trop-1 were analyzed at
      successive stages of tumor progression in vitro and in vivo. The findings show
      that Trop-1 is expressed at early stages of tumor development, eg, in dysplastic
      lesions and immortalized cells, is sufficient to stimulate cell growth of
      expressing transformed cells, and is required for tumor growth in vivo.
      CONCLUSIONS: The findings identify Trop-1 as a novel determinant of cell growth
      at early stages of tumor development and as a marker of early stages of
      development in normal tissues and in cancer, making this molecule a candidate for
      novel diagnostic and therapeutic procedures.

PMID- 17559146
TI  - Updated efficacy and toxicity analysis of irinotecan and oxaliplatin (IROX) :
      intergroup trial N9741 in first-line treatment of metastatic colorectal cancer.
AB  - BACKGROUND: Efficacy and toxicity of oxaliplatin (Eloxatin; Sanofi-Aventis,
      Paris, France) combined with irinotecan (IROX) were examined in 383 patients
      enrolled on the IROX arm of Intergroup Study N9741. METHODS: This IROX regimen
      was oxaliplatin 85 mg/m(2) and irinotecan 200 mg/m(2) administered every 3 weeks.
      The relation between adverse events on IROX to selected characteristics was
      analyzed. Time to progression (TTP), response rate, and overall survival for
      patients treated with IROX compared with patients treated with oxaliplatin with 5
      fluorouracil (FOLFOX) were updated in this article. RESULTS: Grade >or=3
      gastrointestinal and hematologic toxicities were common with 39% patients
      experiencing neutropenia, 28% diarrhea, and 21% vomiting. Patients ages >70 years
      experienced higher rates of grade >or=3 toxicity, with significantly higher rates
      of grade >or=3 hematologic toxicities (P = .02). Long-term toxicity was uncommon,
      and nearly all cases of grade >or=3 neurotoxicity resolved within 10 months.
      Fifty-two percent of patients required dose reductions for adverse events, and
      26% experienced 119 hospitalizations related to complications of treatment or
      their disease, with 5 treatment-related deaths. This analysis confirmed prior
      findings that FOLFOX is superior to IROX in terms of response rate (43% vs 36%, p
      = 0.002), TTP (9.2 months vs 6.7 months, P < .0001), and overall survival (19.5
      months vs 17.3 months, P = .0001). CONCLUSIONS: IROX was found to be less active
      than FOLFOX but with a similar toxicity profile except in patients ages >70
      years. Although IROX may be considered in patients intolerant of 5-FU or in
      patients known to have a dihydropyrimidine dehydrogenase (DPD) deficiency, it
      should be used with caution in older patients.

PMID- 17559147
TI  - Serum EGFR and serum HER-2/neu are useful predictive and prognostic markers in
      metastatic breast cancer patients treated with metronomic chemotherapy.
AB  - BACKGROUND: Metronomic chemotherapy has been demonstrated to be of value in
      patients with advanced breast cancer. No reliable markers of response are
      available. In breast tumor, HER-2/neu is a prognostic factor, whereas no definite
      data exist for EGFR. The aim of the study was to evaluate the prognostic and
      predictive role of serum HER-2/neu and serum EGFR in breast cancer patients
      treated with low-dose chemotherapy. METHODS: Serum levels of HER-2/neu (n = 135)
      and of EGFR (n = 113) were prospectively determined before the start of
      chemotherapy, after 2 months of treatment, and when progressive disease was
      diagnosed. RESULTS: Elevated (>15 ng/mL) serum HER-2/neu before the start of
      chemotherapy was not associated with response rate, whereas elevated serum HER
      2/neu at 2 months was significantly associated with reduced long-term clinical
      benefit (24 weeks) (P < .001), as well as changes in HER-2/neu levels between
      baseline and 2 months (P < .0001). Multivariate analysis identified a >or=20%
      increase of serum HER-2/neu as an independent factor for progression-free
      survival (PFS). Kinetics of serum HER-2/neu were significantly associated with
      PFS (P < .0001) and overall survival (OS) (P = .015). Low baseline serum levels
      of EGFR (<45 ng/mL) were predictive of reduced response rate both at 2 months (P
      = .031) and after 24 weeks (P = .022). Moreover, they were significantly
      associated with reduced PFS (P = .016) and OS (P = .015). CONCLUSIONS: Serum HER
      2/neu and EGFR may represent useful markers for early prediction of probability
      of response, PFS, and OS in patients with advanced breast cancer treated with
      metronomic chemotherapy.

PMID- 17559148
TI  - The effects of discontinuing pioglitazone in patients with nonalcoholic
      steatohepatitis.
AB  - A pilot study of a 48-week course of pioglitazone demonstrated significant
      improvements in the biochemical and histological features of nonalcoholic
      steatohepatitis (NASH). The aim of the study was to assess the effects of
      stopping pioglitazone. Twenty-one patients with NASH were treated with
      pioglitazone (30 mg/day) for 48 weeks and underwent baseline and end-of-treatment
      evaluation including liver biopsy. Thirteen patients were followed for at least
      48 weeks after stopping therapy and 9 underwent repeat liver biopsy. Statistical
      comparisons were made to evaluate whether discontinuation of pioglitazone
      resulted in a reversal of improvements seen on therapy. Stopping pioglitazone was
      associated with subsequent elevation in serum alanine aminotransferase levels
      (from 34 +/- 13 to 70 +/- 39 IU/l), decrease in adiponectin (from 9.7 +/- 9.1 to
      5.1 +/- 4.5 microg/ml), worsening insulin sensitivity (HOMA Index: from 2.9 +/-
      1.8 to 5.5 +/- 5.4), and increase in total hepatic fat (from 30% +/- 32% to 71%
      +/- 33%) despite no change in average body weight compared to the end of
      treatment. Repeat liver biopsy in 9 patients revealed significant worsening of
      parenchymal inflammation (from 1.2 +/- 0.7 to 2.9 +/- 1.1) and steatosis (from
      0.9 +/- 0.6 to 2.1 +/- 1.3) but no change in fibrosis (from 1.1 +/- 1.2 to 1.2 +/
      1.3). NASH was again present on liver biopsy in 7 patients. CONCLUSION: These
      findings suggest that long-term therapy with pioglitazone may be necessary to
      maintain improvements in disease activity in patients with NASH, although weight
      gain during treatment may ultimately limit its beneficial effects.

PMID- 17559149
TI  - Tauroursodeoxycholic acid inhibits apoptosis induced by Z alpha-1 antitrypsin via
      inhibition of Bad.
AB  - Z alpha-1 antitrypsin (AAT) deficiency is a genetic disease associated with
      accumulation of misfolded AAT in the endoplasmic reticulum (ER) of hepatocytes.
      ZAAT-expressing cells display ER stress responses including nuclear factor kappaB
      activation and apoptosis. Using an in vitro model of ZAAT ER accumulation, we
      investigated the mechanism of ZAAT-mediated ER-induced apoptosis and evaluated
      methods to inhibit this process. Here we demonstrate that expression of ZAAT, but
      not normal MAAT, in HEK293 cells leads to cleavage and activation of caspase-4
      and induces apoptosis that is characterized by activation of caspase-3 and
      caspase-7 and DNA fragmentation. Similar effects are also induced using the ER
      agonist thapsigargin. A caspase-4-specific short interfering RNA (siRNA) does not
      impair ZAAT-induced caspase-3/7 activation or cell death in these cells. However,
      inhibition studies performed using tauroursodeoxycholic acid (TUDCA) demonstrate
      its ability to inhibit caspase-4 and caspase-3/7 activation, mitochondrial
      cytochrome c release, and caspase-3 cleavage induced by ZAAT and to promote cell
      survival. The mechanism by which TUDCA (tauroursodeoxycholic acid) promotes cell
      survival in ZAAT-expressing cells involves phosphorylation and inactivation of
      the proapoptotic factor Bad. TUDCA is unable to rescue cells from apoptosis or
      phosphorylate Bad in the presence of LY294002, a selective P-I-3-kinase
      inhibitor. CONCLUSION: These data show that caspase-4 is not essential for ZAAT
      induced apoptosis in HEK293 cells and implicates P-I-3-kinase and Bad as
      potential therapeutic targets for the liver disease associated with ZAAT
      deficiency.

PMID- 17559150
TI  - Identification of PFTAIRE protein kinase 1, a novel cell division cycle-2 related
      gene, in the motile phenotype of hepatocellular carcinoma cells.
AB  - Metastasis is a major cause of cancer morbidity and mortality in individuals with
      hepatocellular carcinoma (HCC), yet little is known about the underlying
      molecular basis. Using genetic information derived from chromosome-based
      comparative genomic hybridization, we have reported previously on regional
      chromosome 7q21-q22 gains in close association with HCC progression. In this
      study, we undertook cDNA microarray-based comparative genomic hybridization, to
      examine the 7q21-q22 region for the involved gene(s) in HCC. High-resolution
      mapping analysis highlighted 7 candidates, namely PFTAIRE protein kinase 1
      (PFTK1), ODAG, CDK6, CAS1, PEX1, SLC25A, and PEG10, within the region.
      Quantitative reverse transcription (RT)-PCR evaluation further indicated
      upregulation of a single candidate gene, PFTK1, that correlated significantly
      with both advanced metastatic HCCs (P = 0.032) and tumor microvascular invasion
      (P = 0.012). Given that little is known about the function(s) of PFTK1, which is
      a novel cell division cycle (Cdc)2-related gene, we examined its potential role
      in the motile phenotype of HCC cells by both ectopic expression and knockdown
      investigations. RNA-interference knockdown of PFTK1 in invasive Hep3B cells
      resulted in a significant reduction in cell invasion, chemotactic migration, and
      cell motility (P < 0.001). Conversely, ectopic expression of PFTK1 in noninvasive
      HKCI-C3 cells induced substantial cellular invasion and migration (P < or =
      0.007). In neither cell line was there any effect on cell viability.
      Immunofluorescence showed marked filamentous actin polymerizations in PFTK1
      expressing cells. CONCLUSION: In this study, we have thus provided preliminary
      evidence that overexpression of PFTK1 may confer a motile phenotype in malignant
      hepatocytes that accounts for the association of upregulation of this gene in
      metastatic HCC.

PMID- 17559151
TI  - Human leukocyte antigen-associated sequence polymorphisms in hepatitis C virus
      reveal reproducible immune responses and constraints on viral evolution.
AB  - CD8(+) T cell responses play a key role in governing the outcome of hepatitis C
      virus (HCV) infection, and viral evolution enabling escape from these responses
      may contribute to the inability to resolve infection. To more comprehensively
      examine the extent of CD8 escape and adaptation of HCV to human leukocyte antigen
      (HLA) class I restricted immune pressures on a population level, we sequenced all
      non-structural proteins in a cohort of 70 chronic HCV genotype 1a-infected
      subjects (28 subjects with HCV monoinfection and 42 with HCV/human
      immunodeficiency virus [HIV] coinfection). Linking of sequence polymorphisms with
      HLA allele expression revealed numerous HLA-associated polymorphisms across the
      HCV proteome. Multiple associations resided within relatively conserved regions,
      highlighting attractive targets for vaccination. Additional mutations provided
      evidence of HLA-driven fixation of sequence polymorphisms, suggesting potential
      loss of some CD8 targets from the population. In a subgroup analysis of mono- and
      co-infected subjects some associations lost significance partly due to reduced
      power of the utilized statistics. A phylogenetic analysis of the data revealed
      the substantial influence of founder effects upon viral evolution and HLA
      associations, cautioning against simple statistical approaches to examine the
      influence of host genetics upon sequence evolution of highly variable pathogens.
      CONCLUSION: These data provide insight into the frequency and reproducibility of
      viral escape from CD8(+) T cell responses in human HCV infection, and clarify the
      combined influence of multiple forces shaping the sequence diversity of HCV and
      other highly variable pathogens.

PMID- 17559152
TI  - Treatment of chronic hepatitis C virus genotype 1 with peginterferon, ribavirin,
      and epoetin alpha.
AB  - Successful treatment of chronic HCV with peginterferon (PEGIFN) and ribavirin
      (RVN) is often limited by anemia. We performed the present study to determine if
      utilizing epoetin alpha (EPO) with or without a higher dose of RVN could enhance
      sustained virologic response (SVR). We randomized 150 treatment-naive patients
      with chronic HCV genotype 1 into 3 treatment groups: (1) PEGIFN alpha-2b (1.5
      microg/kg/week) + weight-based RVN (WBR) 13.3 mg/kg/day (800 to 1400 mg/day); (2)
      PEGIFN alpha-2b + WBRVN + EPO (40,000 U/week); or (3) PEGIFN alpha-2b + higher
      dose WBR 15.2 mg/kg/day (1000 to 1600 mg/day) + EPO. We initiated EPO at the
      onset of therapy to maintain the hemoglobin between 12 and 15 g/dL. When
      required, we reduced RVN by 200-mg steps. African Americans compose 36% of the
      population. A significantly smaller percentage of group 2 patients had a decline
      in hemoglobin to less than 10 g/dL (9% versus 34%; P < 0.05) and required that
      the RVN dose be reduced (10% versus 40%; P < 0.05) compared to group 1 patients.
      Despite this, SVR was similar in these groups (19% to 29%). SVR was significantly
      greater (P < 0.05) in group 3 patients (49%). This resulted from a significant
      decline (P < 0.05) in relapse rate; only 8% versus 38% for groups 1 and 2.
      CONCLUSION: We conclude that using EPO in all subjects at the initiation of
      PEGIFN and RVN treatment will not enhance SVR given the same starting dose of
      RVN. In contrast, a higher starting dose of RVN was associated with a lower
      relapse rate and higher rate of SVR.

PMID- 17559153
TI  - Cytochrome P450IID6-specific CD8 T cell immune responses mirror disease activity
      in autoimmune hepatitis type 2.
AB  - Autoimmune hepatitis type 2 (AIH-2) is a severe organ-specific disorder
      characterized by liver kidney microsomal antibody type 1 targeting cytochrome
      P4502D6 (CYP2D6). Growing evidence implicates the involvement of CD8 T cell
      immune responses in its pathogenesis. We investigated CYP2D6-specific CD8 T cell
      human leukocyte antigen (HLA)-A2 restricted responses in AIH-2 (20 patients, 11
      HLA-A2+). Binding affinity of CYP2D6 peptides to HLA-A2 was predicted by the
      algorithm SYFPEITHI and assessed in vivo by T2 cell assays. CD8 T cell interferon
      (IFN)-gamma production was assessed via intracellular cytokine staining,
      cytotoxicity via chromium release assay, and frequency of circulating and
      intrahepatic CYP2D6-specific CD8 T cells via tetramer staining. CYP2D6-specific
      CD8 T cell reactivity was tested at diagnosis and during treatment and correlated
      with indices of disease activity. Seven CYP2D6 peptides with high HLA-A2 binding
      affinity colocalizing with known B cell or CD4 T cell epitopes were selected.
      Five sequences inducing high levels of IFN-gamma were used for HLA-A2 tetramer
      construction. Frequency, IFN-gamma production, and cytotoxicity of CYP2D6
      specific CD8 T cells were higher at diagnosis than during treatment. Intensity of
      CYP2D6-specific CD8 T cell responses correlated with disease activity. Immune
      responses to CYP2D6(245-254) were the strongest both at diagnosis and during
      treatment. CONCLUSION: HLA-A2-restricted, CYP2D6-specific CD8 T cell immune
      responses vary according to disease stage and correlate with hepatocyte damage.
      CD8 T cell targets on CYP2D6-in particular CYP2D6(245-254)-may be the focus of
      novel immune intervention in AIH-2. (HEPATOLOGY 2007.).

PMID- 17559154
TI  - X protein of hepatitis B virus functions as a transcriptional corepressor on the
      human telomerase promoter.
AB  - The X protein of hepatitis B virus (HBx) is essential for transactivation of
      hepatitis B viral and host cellular genes. It has been specifically implicated in
      the development of hepatocellular carcinoma; however, the molecular mechanism
      remains unknown. Telomeres, the DNA-protein complexes at the ends of eukaryotic
      chromosomes, protect chromosomes from degradation at the terminal regions, fusion
      with a broken DNA end, and inappropriate recombination. The shortening of
      telomeres that occurs during hepatocellular carcinogenesis has been well studied.
      In the present study, we isolated an HBx isoform that resulted in telomere
      shortening in hepatoma cell lines. We found that this HBx isoform down-regulated
      the expression of human telomerase by transcriptionally repressing its promoter.
      To further determine the molecular mechanism, we examined human telomerase
      promoter and identified myc-associated zinc finger protein (MAZ) as a
      transcriptional repressor of the promoter. We found that the HBx isoform achieved
      transcriptional suppression of human telomerase by enhancing MAZ binding to its
      consensus sequence in the promoter through physical association with MAZ.
      CONCLUSION: The data suggest that HBx can induce telomere shortening by acting as
      a transcriptional corepressor of MAZ on the human telomerase promoter.

PMID- 17559155
TI  - Guardianship determinations by judges, attorneys, and guardians.
AB  - Guardianship is intended to protect incapacitated individuals through the
      appointment of a surrogate decision maker. Little is known about how judges,
      attorneys, and professional guardians assess the need for guardianship, to what
      extent they apply statutory guidelines when making these determinations, and how
      their decisions compare. Three groups of participants (probate judges, elder law
      attorneys, and professional guardians) read vignettes portraying older adults
      that varied in the extent to which the evidence supported the appointment of a
      guardian. They were asked about the appropriateness of various resolutions.
      Participants were reluctant to endorse full guardianship even when warranted by
      the evidence and preferred informal, family-based interventions that do not
      involve legal action. Professional groups did not always agree on the appropriate
      resolutions, suggesting that one's professional orientation may play a role in
      perceptions of older adults.

PMID- 17559156
TI  - Robert D Miller MD, PhD: September 4, 1941-July 13, 2006.

PMID- 17559157
TI  - Introduction to this issue: elder issues.

PMID- 17559158
TI  - Configurational assignment of carbon, silicon and germanium containing propynal
      oximes by means of 13C-1H, 13C-13C and 15N-1H spin-spin coupling constants.
AB  - Configurational assignment of five carbon, silicon and germanium containing
      propynal oximes has been carried out by means of experimental measurements and
      high-level ab initio calculations of their 13C-1H, 13C-13C and 15N-1H spin-spin
      coupling constants. The title compounds were shown to exist in the nonequilibrium
      mixture of E and Z isomers with the energy difference of less than 0.3 kcal/mol
      calculated at the MP2/6-311G** level.

PMID- 17559159
TI  - 2J(29Si-O-29Si) coupling constants in oligosiloxanes.
AB  - The absolute values of spin-spin couplings between (29)Si nuclei in siloxanes,
      (2)J((29)Si-O-(29)Si), were determined. The couplings are small and cover a
      narrow range of values (0-5 Hz). The coupling constants depend on the branching
      or on the number of electronegative substituents on the Si-O-Si moiety.

PMID- 17559160
TI  - Improved DECRA processing of DOSY data: correcting for non-uniform field
      gradients.
AB  - Mixture analysis using PFG-NMR (DOSY) data is, for many chemists, a valuable and
      increasingly popular technique where the NMR signals of different species are
      separated according to their diffusion coefficients. Where NMR signals overlap,
      however, it is often difficult to extract the spectra of pure components from
      experimental data. In such situations, it can often be helpful to use
      multivariate methods, which exploit all the available signal covariance, to
      resolve the spectra of the components of a mixture. The best-established and by
      some way the quickest such method, DECRA (Direct Exponential Curve Resolution
      Algorithm), unfortunately requires that data conform to a pure exponential decay
      as a function of gradient strength squared, while experimental data typically
      deviate significantly from this. If this deviation is known, the performance of
      DECRA can be greatly improved for components with similar diffusion coefficients
      by adjusting the choice of gradient strengths used.

PMID- 17559161
TI  - Conformational exchange in pimonidazole--a hypoxia marker.
AB  - Pimonidazole is one of a series of nitroimidazole compounds that is widely used
      as a marker for qualitative and quantitative assessment of tumour hypoxia. We
      have observed a novel dynamic conformational exchange process in this molecule in
      aqueous solution. By a combination of 1H, 13C, two-dimensional 1H-1H EXchange
      SpectroscopY (EXSY) and spectral simulation, we unambiguously attribute the
      conformational exchange process to flipping of the six-membered heterocyclic
      ring.

PMID- 17559162
TI  - 13C-detected IPAP-INADEQUATE for simultaneous measurement of one-bond and long
      range scalar or residual dipolar coupling constants.
AB  - The sensitivity of cryoprobes, which are rapidly becoming available, means that
      the measurement of coupling constants involving 13C, 13C pairs at the natural
      abundance of 13C can now, in principle, be done by using tens rather then
      hundreds of milligrams of compounds. However, a robust method that would yield
      reliable values of small long-range carbon--carbon coupling constants is still
      missing. In this Communication, we describe a novel 13C-detected incredible
      natural-abundance double-quantum transfer experiment (INADEQUATE) experiment for
      simultaneous correlation of one-bond and long-range 13C- 13C pairs and the
      measurement of both types of coupling constants in 13C natural abundance samples.
      This method yields accurate values of one-bond and long-range coupling constants
      by manipulation of pure phase in-phase (IP) and antiphase (AP) doublets, and is
      referred to as 13C-detected IPAP-INADEQUATE. It is illustrated by the measurement
      of interglycosidic (3)J(CCOC) coupling constants in a disaccharide molecule
      providing important information about the conformation of the glycosidic linkage.
      Owing to the simplicity of INADEQUATE spectra the carbon-carbon coupling
      constants are particularly suitable for studies of partially oriented molecules
      through the measurement of carbon-carbon residual dipolar couplings (RDCs). An
      example of this approach is presented. We expect the method to find a variety of
      applications in the conformational analysis of small molecules, determination of
      diastereoisomers and enantiomers, and studies of molecules in aligned media.

PMID- 17559163
TI  - 1H, 13C, 15N and 19F NMR study of acetylation products of heterocyclic
      thiosemicarbazones.
AB  - Novel 2-acetylamino-4-acetyl-5-aryl(heteryl)-1,3,4-thiadiazolines, 2-acetylamino
      5-aryl(heteryl)-1,3,4-thiadiazoles, and some of their salts were prepared and
      studied by multinuclear 1H, 13C, 15N, 19F and 2D NMR spectroscopy. The
      acetylation of thiosemicarbazones is accompanied by ring closure to form the
      corresponding 1,3,4-thiadiazolines and 1,3,4-thiadiazoles. 15N NMR spectroscopy
      is a unique method for the identification of thiadiazole pyridinium salts.

PMID- 17559164
TI  - Structure elucidation of thermal degradation products of amlodipine.
AB  - Thermal degradation of amlodipine base causes intramolecular reactions affording
      three cyclic products, referred to as AMLDEG-I, AMLDEG-II, and AMLDEG-III,
      respectively. AMLDEG-I is a cyclized product formed by intramolecular elimination
      of ammonia from amlodipine. AMLDEG-II is a positional isomer of AMLDEG-I. AMLDEG
      III is also intramolecular cyclisation product. The three degradation products
      were isolated by column chromatography and characterized by FT-IR and 1H and 13C
      NMR spectroscopy data. The AMLDEG-III was crystallized and its structure was
      solved by single crystal X-ray diffraction (SXRD).

PMID- 17559165
TI  - DFT studies of the conformational/structural dependencies of geminal 1H,1H scalar
      coupling 2J(H,H') in substituted methanes.
AB  - A study is presented of the structural dependencies for scalar, interproton J
      coupling across two bonds in a series of substituted methanes. The coupled
      perturbed, density functional theory method with a B3PW91 functional and aug-cc
      pVTZ-J basis sets is used to examine coupling between geminal protons (2)J(H,H')
      in methane and a series of substituted compounds CH(3)X (X = CH3, CH(2)CH(3),
      CH=CH2, CH=O, and NH2) as functions of the dihedral angle phi measured about the
      C1-X2 bonds. All four contributions are obtained but all conformational effects
      are dominated by the Fermi contact term. Simple linear combination of atomic
      orbitals (LCAO)-molecular orbital (MO) sum-over-states methods are used to
      examine the relationships of the coupling constants with dihedral angles as well
      as internal H-C-H and H-C1-X2 angles. This study explores some novel aspects of
      geminal H-H coupling including an analysis of the asymmetry in the conformational
      dependencies arising from non-next-nearest neighbor interactions. For each of the
      substituted methanes, explicit trigonometric/exponential expressions are given
      and these accurately reproduce the (2)J(H,H') structural dependencies with
      standard deviations usually less than 0.03 Hz. The molecular structures for
      representative bicyclic molecules were fully optimized, and DFT results for
      (2)J(H,H') reproduce all the trends in the experimental data. A discussion is
      given on the applicability of the equations for H--H coupling in the substituted
      methanes to coupling in the bicyclic molecules.

PMID- 17559166
TI  - Quantum chemical and nuclear magnetic resonance spectral studies on molecular
      properties and electronic structure of berberine and berberrubine.
AB  - The structural and electronic properties of berberine and berberrubine have been
      studied extensively using density functional theory (DFT) employing B3LYP
      exchange correlation. The geometries of these molecules have been fully optimized
      at the B3LYP/6-311G** level. The chemical shift of 1H and 13C resonances in NMR
      spectra of these molecules have been calculated using the gauge invariant atomic
      model (GIAO) method as implemented in Gaussian 98. One- and two-dimensional HSQC
      (1H-13C), HMBC (1H-13C) and ROESY (1H-1H) spectra were recorded at 500 MHz for
      the berberine molecule in D(2)O solution. All proton and carbon resonances were
      unambiguously assigned, and inter-proton distances obtained from ten observed NOE
      contacts. A restrained molecular dynamics (RMD) approach was used to get the
      optimized solution structure of berberine. The structure of berberine and
      berberrubine molecules was also obtained using the ROESY data available in
      literature. Comparison of the calculated NMR chemical shifts with the
      experimental values revealed that DFT methods produce very good results for both
      proton and carbon chemical shifts. The importance of the basis sets to the
      calculated NMR parameters is discussed. It has been found that calculated
      structure and chemical shifts in the gas phase predicted with B3LYP/6-311G** are
      in very good agreement with the present experimental data and the measured values
      reported earlier.

PMID- 17559167
TI  - 1H and 13C NMR spectral data of new saponins from Cordia piauhiensis.
AB  - Two new bidesmoside triterpenoid saponins were isolated from stems of Cordia
      piauhiensis. Their structures, characterized as 3-O-alpha-L-rhamnopyranosyl-(1 -
      > 2)-beta-D-glucopyranosyl pomolic acid 28-O-beta-D-glucopyranosyl ester (1) and
      3-O-alpha-L-rhamnopyranosyl-(1 --> 2)-beta-D-glucopyranosyl oleanolic acid 28-O
      beta-D-glucopyranosyl-(1 --> 6)-beta-D-glucopyranosyl ester (2), were
      unequivocally established after extensive NMR (1H, 13C, DEPT 135 degrees, COSY,
      HSQC, HMBC, TOCSY, and NOESY) studies.

PMID- 17559168
TI  - Granny, (don't) get your gun: competency issues in gun ownership by older adults.
AB  - This article explores the possible risks associated with gun ownership by older
      adults. We summarize existing regulations on who may own firearms, especially
      with respect to age. We then present data on older gun owners and violence
      committed by older adults in general, followed by a discussion of gun violence
      perpetrated by gun owners whose functional and cognitive abilities have declined,
      perhaps as a result of dementia. For comparison purposes, we review regulations
      on driving among older adults, drawing parallels to gun ownership. The paper
      concludes with recommendations for ensuring the safety of older gun owners and
      others, balanced against citizens' right to bear arms, and with some directions
      for research.

PMID- 17559169
TI  - Impact of cellular lifespan on the T cell receptor repertoire.
AB  - Pro-survival members of the Bcl-2 family are potent inhibitors of cell death and
      determine the lifespan of immature thymocytes by counteracting the intrinsically
      active apoptotic program in these cells. BH3-only proteins are potent antagonists
      of Bcl-2-like molecules and regulate death and survival of lymphocytes during
      their development and homeostasis. The intrinsic lifespan of CD4(+)8(+) double
      positive thymocytes was reported to actively shape the diversity of the immune
      repertoire, since mice overexpressing Bcl-x(L) were reported to show a bias
      towards the usage of distal 3' Jalpha elements 1. To gain support for this
      concept, we analyzed TCRalpha rearrangements in T lymphocytes that show an
      extended lifespan due to either loss of the BH3-only protein Bim or
      overexpression of Bcl-2. A minor but reproducible skewing towards the usage of
      the more distal 3' Jalpha elements was observed in developing thymocytes and
      mature T cells from bim(-/-) and vav-bcl-2 transgenic mice, indicating that
      prolonged survival of double-positive thymocytes does have a significant impact
      on the selected TCRalpha repertoire. However, the changes that we observed were
      less pronounced than those found in lck-bcl-x(L) transgenic mice, pointing
      towards qualitative differences between Bcl-2- and Bcl-x(L)-mediated cell death
      inhibition during T cell development.

PMID- 17559170
TI  - Modulation of Valpha19 NKT cell immune responses by alpha-mannosyl ceramide
      derivatives consisting of a series of modified sphingosines.
AB  - We have demonstrated that analogues of alpha-mannosyl ceramide (alpha-ManCer)
      consisting of a series of immunosuppressive 2-aminoalcohol derivatives in place
      of sphingosine promote a greater immune response from mouse invariant Valpha19
      Jalpha26 (AV19-AJ33) TCR-bearing NKT (Valpha19 NKT) cells than alpha-ManCer
      itself. To further characterize the immune responses of Valpha19 NKT cells to the
      alpha-ManCer analogues, cytokine production by the cells was examined in detail.
      We found that certain alpha-ManCer derivatives individually induced either Th1-
      or Th2-dominant cytokine production in culture. The Th1- or Th2-biased immune
      responses of Valpha19 NKT cells were dependent on MHC class I-like MR1, since
      they were induced by coculture with the MR1 transfectants previously loaded with
      the glycolipids and were inhibited in the presence of anti-MR1 antiserum.
      Presumably, the recognition of the alpha-mannosyl residue of the alpha-ManCer
      analogues by the invariant TCR is individually modulated, depending on the
      altered interaction with the groove of the antigen-presenting MR1. Priming of the
      Valpha19 invariant TCR-transgenic mice in vivo with these glycolipid derivatives
      resulted in the induction of the Th1- or Th2-biased immune responses. Thus, these
      alpha-ManCer derivatives are likely to be useful in immunotherapy for either Th1
      or Th2 excess autoimmune diseases, modulating the function of Valpha19 NKT cells.

PMID- 17559171
TI  - House dust mite allergen activates human eosinophils via formyl peptide receptor
      and formyl peptide receptor-like 1.
AB  - The objective was to evaluate which receptors house dust mite (HDM) and birch
      pollen extracts engage to activate human eosinophils. Chemotaxis and
      degranulation were studied in eosinophils pretreated with pertussis toxin and
      other antagonists of G protein-coupled receptors, e.g. the formyl peptide
      receptor (FPR), CC chemokine receptor 3 (CCR3) and leukotriene receptor B4
      (LTB(4)R). Inhibition of the FPR as well as desensitization of the receptor
      rendered eosinophils anergic to activation by the allergens. Blockade of CCR3 or
      LTB(4)R did not affect eosinophilic reactivity. It was determined by PCR that
      human eosinophils express the FPR family members FPR and FPR-like 1 (FPRL1). HDM,
      unlike birch pollen, evoked calcium fluxes in HL-60 cells transfected with FPR or
      FPRL1. Although both allergens gave rise to calcium transients in neutrophils,
      which also express FPR and FPRL1, only the HDM response was decreased by the FPR
      antagonist. Moreover, neutrophils migrated toward HDM but not to birch pollen.
      Eosinophils pretreated with inhibitors of MAPK p38, ERK1/2 or protein kinase C
      exhibited diminished responsiveness to the aeroallergens. This study indicates
      that FPR and FPRL1 mediate the activation of eosinophils by HDM, whereas birch
      pollen employs other pathways shared with FPR to activate human eosinophils.

PMID- 17559172
TI  - CD28:B7 interaction is necessary for the protective effect of T cell vaccination
      in EAE.
AB  - The mechanisms of T cell vaccination (TCV) are still unclear, especially the
      molecular interactions for recognition of autoreactive T cells by the immune
      system. Here we investigated the role of CD28:B7 interaction in TCV-induced
      protection in the murine EAE model. We demonstrate that there is increased
      expression of both B7-1 and B7-2 on autoreactive Th1 cells compared to Th2 cells.
      Blockade of B7 on the vaccinating autoreactive T cell surface or blockade of CD28
      in recipient mice reduced the protective effect of TCV. Furthermore, we showed
      that TCV significantly inhibited Ag-specific CD4 and CD8 T cell proliferation and
      decreased Ag-specific IFN-gamma production by CD4 T cells in mice undergoing TCV,
      and blocking of B7 on the surface of vaccinating T cells reduced this inhibition
      on Ag-specific CD4 and CD8 T cell proliferation, more significantly on Ag
      specific CD4 T cell proliferation. These data indicated that B7 expression on
      autoreactive T cells is necessary for the recognition of autoreactive T cells by
      the immune system and subsequent protection from EAE in mice undergoing TCV.

PMID- 17559173
TI  - IL-2Rbeta links IL-2R signaling with Foxp3 expression.
AB  - Immunological tolerance to self antigens is a tightly regulated process. Recent
      work has demonstrated that the forkhead family member Foxp3 is a critical element
      in the differentiation and function of mouse CD4(+)CD25(+) regulatory T cells
      (Treg). Recent work has suggested an important role for IL-2 in the development
      and maintenance of Treg. To directly assess the effect of IL-2 signaling on Treg
      development and function, we analyzed mice that were genetically deficient in
      components of the IL-2 receptor (IL-2R). Mice lacking CD25 (IL-2Ralpha) displayed
      a slight decrease in Treg within the thymus, while peripheral numbers are
      unchanged. In contrast, we found that mice deficient in CD122 (IL-2Rbeta) had a
      profound reduction in both thymic and peripheral Treg, coinciding with more rapid
      development of a fatal lymphoproliferative disease. Expression of a Foxp3
      transgene restored Treg and protected against the onset of autoimmunity. Thus, a
      signal mediated by IL-2Rbeta is essential for the development and homeostasis of
      Foxp3(+) Treg in vivo.

PMID- 17559174
TI  - Antigen-specific cytotoxic T lymphocytes protect against lethal West Nile virus
      encephalitis.
AB  - Infection with West Nile virus (WNV) causes fatal encephalitis in
      immunocompromised animals. Previous studies in mice have established that T cell
      protection is required for clearance of WNV infection from tissues and preventing
      viral persistence. The current study assessed whether specific WNV peptide
      epitopes could elicit a cytotoxic T lymphocyte (CTL) response capable of
      protecting against virus infection. Hidden Markov model analysis was used to
      identify WNV-encoded peptides that bound the MHC class I proteins K(b) or D(b).
      Of the 35 peptides predicted to bind MHC class I molecules, one immunodominant
      CTL recognition peptide was identified in each of the envelope and non-structural
      protein 4B genes. Addition of these but not control peptides to CD8(+) T cells
      from WNV-infected mice induced IFN-gamma production. CTL clones that were
      generated ex vivo lysed peptide-pulsed or WNV-infected target cells in an antigen
      specific manner. Finally, adoptive transfer of a mixture of envelope- and non
      structural protein 4B-specific CTL to recipient mice protected against lethal WNV
      challenge. Based on this, we conclude that CTL responses against immundominant
      WNV epitopes confer protective immunity and thus should be targets for inclusion
      in new vaccines.

PMID- 17559175
TI  - Protective capacity and epitope specificity of CD8(+) T cells responding to
      lethal West Nile virus infection.
AB  - West Nile virus (WNV) is a small, positive-strand RNA virus belonging to the
      Flaviviridae genus, which causes lethal encephalitis in a subset of infected
      birds and mammals. In humans, WNV exhibits pronounced age-related morbidity and
      mortality, but the basis of this effect is unclear, and the molecular and
      cellular parameters of the host-WNV infection are just beginning to be
      elucidated. Indeed, numerous mechanisms were implicated in protection in vivo
      against WNV (IFN-I and IFN-gamma, antibody, C', CD8 and CD4 T cells), but the
      individual importance of each one of these remains unclear. Here, we show that
      transfer of highly enriched naive CD8(+ )T cells protects the majority of
      alymphoid mice against lethal WNV infection. To substantiate and expand this
      finding, we defined the peptide specificity of the CD8 response in H-2b mice and
      used a panel of identified peptides to map one dominant (NS4b (2248-2256)) and
      several subdominant epitopes. The hierarchy of these epitopes was stably
      maintained in the memory responses. Most importantly, CTL lines directed against
      these peptides conferred protection against lethal WNV infection in direct
      proportion to the epitope immunodominance. These results provide a springboard
      for future characterization of T cell responses against WNV and demonstrate, for
      the first time, that CD8 T cells can single-handedly protect from this disease.

PMID- 17559179
TI  - Endothelial cell-matrix interactions determine maturation of dendritic cells.
AB  - The fate of allo- and xenogeneic endothelial cell (EC) implants is regulated by
      EC-matrix interactions. While free EC are destroyed by a vigorous immune
      reaction, EC embedded within 3D collagen cells are well tolerated. Given the
      critical role DC serve in immune reactivity, we hypothesized that EC-driven DC
      maturation depends on EC-matrix contact. In marked contrast to DC co-cultured
      with a cytokine cocktail or with allo- and xenogeneic EC grown to confluence on
      2D tissue culture plates, DC exposed to 3D matrix-embedded allo- and xenogeneic
      EC failed to mature, retaining their endocytic activity and exhibiting
      significantly reduced expression of maturation markers (costimulatory molecules,
      HLA-DR, CD83; p <0.01). Matrix-embedded EC also limited cytokine-induced
      maturation and activity of DC. Incubation with matrix-embedded EC inhibited DC
      induction of allogeneic lymphocyte proliferation (p <0.002) and EC cross
      activation (ICAM-1, VCAM-1, HLA-DR, TLR2 and 4; p <0.01). The endothelium in its
      quiescent state is confluent and substrate adherent. The former ensures secretion
      of growth inhibitors rather than promoters, and the latter may ensure immune
      acceptance. We now demonstrate for the first time that interactions of EC with an
      underlying 3D matrix affect the ability of EC to drive DC maturation.

PMID- 17559180
TI  - MHC-peptide-specific antibodies reveal inefficient presentation of an HLA-A*0201
      restricted, Melan-A-derived peptide after active intracellular processing.
AB  - MHC-peptide-specific Fab antibodies binding to HLA-A*0201 complexes presenting
      the wild-type EAAGIGILTV (EAA) or analogue Melan-A 10-mer ELAGIGILTV (ELA)
      peptide were generated to study efficacy of peptide processing and presentation.
      None of the selected Fab antibodies detected the naturally processed EAA/HLA
      A*0201 complex on melanoma tumor cells, confirming the known low peptide number
      on the cell surface. To study the effect of peptide presentation and processing
      in more detail, genes coding for the A27L-mutated Melan-A protein or the
      processed ELA peptide were introduced into HLA-A*0201(+) B cells by infection
      with the respective recombinant vaccinia virus construct producing equimolar
      amounts of GFP-ubiquitin directly linked to the fragment of interest. Correlating
      GFP expression to actual numbers of peptide presented, 1100-2600 [corrected] ELA
      peptides had to be synthesized to be presented by a single MHC class I antigen
      peptide complex. This number increased 10- to 20-fold when ELA peptide
      presentation from the A27L-mutated full length Melan-A protein was studied, since
      16000-52000 [corrected] GFP molecules needed to be synthesized for the detection
      of one ELA peptide. Our results indicate that peptide processing rather than
      presentation is the rate-limiting step in our experimental setting and is much
      more ineffective for Melan-A than has been previously shown for other MHC class I
      restricted epitopes.

PMID- 17559182
TI  - Construction of the "left domain" of haplophytine.

PMID- 17559183
TI  - Increased nuchal translucency thickness and normal karyotype: time for parental
      reassurance.
AB  - OBJECTIVES: To study the outcome of pregnancy in chromosomally normal fetuses
      with increased nuchal translucency thickness (NT), with respect to fetal loss,
      structural defects and genetic syndromes with developmental delay, and to provide
      information that would be helpful for parental counseling on the residual risk of
      adverse outcome when ultrasound findings are normal. METHODS: We reviewed the
      outcome of all pregnancies presenting at the Academic Medical Centre in Amsterdam
      with increased NT between January 1994 and March 2005. Fetal karyotyping and two
      step ultrasound investigation at 13-18 and 20-24 weeks' gestation were offered in
      all cases. Particular attention was paid to the relationship between normal
      karyotype, ultrasound findings at the 20-24-week scan and subsequent pregnancy
      outcome. An adverse outcome was defined as miscarriage, intrauterine death,
      termination of pregnancy at parental request or the finding of one or more
      structural defects or genetic disorders. RESULTS: A total of 675 fetuses with
      increased NT, known karyotype and known pregnancy outcome was analyzed. A
      chromosomal anomaly was detected in 224 (33%) fetuses. In 451 (67%) fetuses, the
      karyotype was normal. The overall incidence of an adverse pregnancy outcome in
      this group was 19% and, when analyzed according to the initial degree of increase
      in NT, the likelihood of an adverse outcome increased with increasing NT, ranging
      from 8% to 80%. 425 fetuses underwent a detailed second-trimester ultrasound
      scan. Anomalies were detected, at the time of ultrasound or after birth, in 54
      (13%) of these fetuses (17 isolated cardiac defects, 14 other structural defects
      and 23 genetic disorders). An adverse pregnancy outcome was recorded in 4% of
      cases in which there were normal findings at the 20-week scan. Seven of these
      cases were classified as 'potentially amenable' to ultrasound detection. With
      exclusion of these cases, the chance of a healthy baby, if the 20-week scan was
      completely normal, was 98%. Genetic syndromes with dysmorphic features and
      neurodevelopmental delay occurred in seven (1.6%) of the fetuses with normal
      karyotype. In three of these pregnancies, non-specific suspicious ultrasound
      findings (nuchal edema, mild pyelectasis, pericardial effusion) were observed at
      the mid-trimester scan and in two others, subtle cardiac defects were detected
      after delivery. In the remaining two cases (0.5%) the mid-trimester scan was
      completely normal and no structural defects were observed after delivery.
      CONCLUSION: After exclusion of chromosomal anomalies, one out of five fetuses
      with increased NT has an adverse pregnancy outcome. The chance of an uneventful
      pregnancy outcome depends on the initial degree of increase in NT. However, if
      the detailed ultrasound examination at around 20 weeks is normal, a favorable
      outcome can be expected with confidence, irrespective of initially increased NT.

PMID- 17559184
TI  - Efficacy of Shirodkar cervical suture in securing hemostasis following surgical
      evacuation of Cesarean scar ectopic pregnancy.
AB  - OBJECTIVES: To assess the efficacy of a Shirodkar cervical suture in arresting
      hemorrhage following surgical removal of a Cesarean scar ectopic pregnancy.
      METHODS: The study included women with an ultrasound diagnosis of Cesarean scar
      ectopic pregnancy who were scheduled for surgical evacuation. After
      administration of general anesthetic, a Shirodkar cervical suture was inserted
      using the standard surgical technique. The suture was left untied and the
      Cesarean scar pregnancy was evacuated under ultrasound guidance using suction
      curettage. Once the pregnancy had been successfully removed, the suture was tied
      and 500 microg ergometrine was administered intravenously to ensure uterine
      contraction. The patients were prescribed prophylactic antibiotics and the suture
      was removed 7 days later in the outpatient setting, under local anesthetic.
      RESULTS: Over a 4-year period a total of 33 Cesarean scar pregnancies were
      diagnosed, and 28 (85%) had surgical evacuation. A cervical suture was necessary
      to achieve hemostasis in 22/28 (79%; 95% CI, 64-94) cases. In the remaining 6/28
      (21%; 95% CI, 6-36) cases, the bleeding was minimal and the suture was not tied.
      The median estimated intraoperative blood loss was 50 (range, 50-1500) mL. Six of
      28 (21%; 95% CI, 6-36) women suffered blood loss > or = 300 mL and two (7%; 95%
      CI, 0-17) required blood transfusion. One woman (5%; 95% CI, 0-14) required
      repeat surgery because of retained products of conception. There were no other
      significant complications and the uterus was preserved successfully in all cases.
      CONCLUSIONS: Insertion of a Shirodkar cervical suture during the evacuation of a
      Cesarean scar pregnancy is an effective method for securing hemostasis; it
      minimizes the need for blood transfusion and ensures preservation of fertility.

PMID- 17559185
TI  - Transvaginal sonographic findings of a large intramural uterine hematoma
      associated with iatrogenic injury sustained at termination of pregnancy.
AB  - We report a case in which a patient presented with severe right lower abdominal
      pain associated with nausea and vomiting 3 days after termination of pregnancy.
      Transvaginal ultrasonography showed a large intramural mass in the anterior
      aspect of the lower segment of an acutely retroflexed uterus. Computed tomography
      and magnetic resonance imaging findings were consistent with an intramural
      hematoma as a result of iatrogenic injury sustained during the preceding
      termination of pregnancy. The patient was managed expectantly. Systematic review
      of the literature confirmed that this is the first report of sonographic findings
      associated with an intramural uterine hematoma some days after the injury
      sustained at termination of pregnancy. This case supports utilization of real
      time ultrasound guidance during intrauterine surgery of selected cases to
      decrease procedure-related morbidity.

PMID- 17559186
TI  - Slow solvation dynamics of a water-nitrobenzene system.
AB  - Very slow changes in solvation taking place in water-saturated nitrobenzene have
      been observed and studied by nuclear magnetic resonance (NMR), Fourier transform
      infrared, and inelastic neutron scattering spectroscopy. These changes are most
      likely caused by the rearrangement of the hydrogen-bonded water network. Lithium
      salts used as the "reporter" species in the (7)Li NMR experiments accelerate this
      reorganization. Results of this work are important for electrochemical studies of
      the nitrobenzene-water interface.

PMID- 17559187
TI  - Ligand effects on dioxygen activation by copper and nickel complexes: reactivity
      and intermediates.
AB  - Copper and nickel complexes having various active-oxygen species M n -O 2 ( n = 1
      or 2), such as trans-(micro-1,2-peroxo)Cu (II) 2, bis(micro-oxo)M (III) 2,
      bis(micro-superoxo)Ni (II) 2, and ligand-based alkylperoxo-M (II) n , can be
      produced by a series of tetradentate tripodal ligands (TMPA analogues) containing
      sterically demanding 6-methyl substituent(s) on the pyridyl group(s), where TMPA
      = tris(2-pyridylmethyl)amine. Roles of the methyl substituent(s) for the
      formation of the active-oxygen species and their oxidation reactivities are
      reported.

PMID- 17559188
TI  - Crystalline host-guest assemblies of steroidal and related molecules: diversity,
      hierarchy, and supramolecular chirality.
AB  - Steroidal bile acids and over 50 of their derivatives serve as the hosts of
      inclusion crystals. These hosts each exhibit their own characteristic inclusion
      behaviors, which have been explored through more than 300 crystallographic data.
      The molecules with three-axial chirality combine in asymmetric fashion to form
      diverse assemblies, which have supramolecular properties, such as recognition and
      dynamics, through cooperative weak interactions. From an overview of these
      results, an analogy emerged: the steroidal assemblies may have hierarchical
      structures, such as primary, secondary, tertiary, and host-guest assemblies,
      similar to proteins. Accordingly, the assemblies with dimensionality bear
      supramolecular chirality, such as three-axial, tilt, helical, bundle, and
      complementary chirality. Such a concept can be extended to other organic
      substances, such as alkaloids and organic salts. These results move in the
      direction of supramolecular crystal engineering.

PMID- 17559189
TI  - Biodelivery of a fullerene derivative.
AB  - Most current nanotoxicology research is focused on examining the influence of
      nanomaterials at the tissue and cellular levels. To explore these interactions on
      the molecular level, new carboxyfullerenes interact with transport proteins at
      the molecular level. The carboxyfullerenes exhibited an unusual mode of binding
      outside the calyx of beta-lactoglobulin (a typical representative of lipocalin
      family of barrier liquid proteins). The complexes were studied by various
      techniques, including mass spectrometry, UV/vis and circular dichroism
      spectroscopy, chromatographic methods, gel electrophoresis, and dynamic light
      scattering. The fullerene ligands were transferred from beta-lactoglobulin to
      human serum albumin (a representative of a blood transport protein), thus
      providing a model of how fullerene-based nanomaterials interact with biomolecules
      and are transported in biological systems.

PMID- 17559190
TI  - Identification of bacteria from two-dimensional resonant-Raman spectra.
AB  - We present the first measurements of two-dimensional resonant-Raman spectra and
      demonstrate the applicability of the method to the identification of bacteria,
      including differentiation of genetically similar species. A new device that
      sequentially illuminates bacteria with different ultraviolet wavelengths and
      measures a spectrum at each was developed for this purpose. We anticipate that
      information within such two-dimensional spectra will allow identification of
      bacteria and chemicals in environments containing multiple organisms and
      chemicals, leading, for example, to instruments that rapidly identify bacteria in
      hospital and food plant settings, for screening large populations, and for
      biochemical-threat warning systems.

PMID- 17559191
TI  - Solution structure of an amyloid-forming protein during photoinitiated hexamer
      dodecamer transitions revealed through small-angle neutron scattering.
AB  - Shape-reconstruction analysis applied to small angle neutron scattering (SANS)
      data is used to determine the in vitro conformations of alpha-chymotrypsin
      oligomers that form as a result of partial unfolding with a photoresponsive
      surfactant. In the presence of the photoactive surfactant under visible light,
      the native oligomers (dimers or compact hexamers) rearrange into expanded
      corkscrew-like hexamers. Converting the surfactant to the photopassive form with
      UV light illumination causes the hexamers to laterally aggregate and intertwine
      into dodecamers with elongated, twisted conformations containing cross-sectional
      dimensions similar to amyloid protofilaments. Secondary-structure measurements
      with FT-IR indicate that this photoinduced hexamer-to-dodecamer association
      occurs through intermolecular beta sheets stabilized with hydrogen bonds, similar
      to amyloid formation. Traditional structural characterization techniques such as
      X-ray crystallography and NMR are not easily amenable to the study of these non
      native protein conformations; however, SANS is ideally suited to the study of
      these associated intermediates, providing direct observation of the mechanism of
      oligomeric formation in an amyloid-forming protein. Combined with photoinitiated
      hexamer-to-dodecamer associations in the presence of the photoresponsive
      surfactant, this study could provide unique insight into the amyloidosis disease
      pathway, as well as novel disease treatment strategies.

PMID- 17559192
TI  - Quantitative structure--activity relationship analysis and molecular dynamics
      simulation to functionally validate nonsynonymous polymorphisms of human ABC
      transporter ABCB1 (P-glycoprotein/MDR1).
AB  - Several preclinical and clinical studies suggest the importance of naturally
      occurring polymorphisms of drug transporters in the individual difference of drug
      response. To functionally validate the nonsynonymous polymorphisms of ABCB1 (P
      glycoprotein/MDR1) in vitro, we generated SNP variant forms (i.e., S400N, R492C,
      R669C, I849M, A893P, A893S, A893T, M986V, A999T, P1051A, and G1063A) and
      expressed them in Sf9 cells. The kinetic properties (Km and Vmax) of those
      variants were analyzed by measuring the ATPase activity to obtain the ATPase
      profile for each variant toward structurally unrelated substrates. On the basis
      of the experimental data, we determined the substrate specificity of ABCB1 WT and
      its variants by the quantitative structure-activity relationship (QSAR) analysis
      method. While several SNP variants appeared to influence the substrate
      specificity of ABCB1, the nonsynonymous polymorphisms of 2677G > T, A, or C at
      amino acid position 893 (Ala > Ser, Thr, or Pro) have great impacts on both the
      activity and the substrate specificity of ABCB1. The A893P variant (2677G > C), a
      rare mutation, exhibited markedly high activity of ATPase toward different test
      compounds. Molecular dynamics (MD) simulation based on a three-dimensional
      structural model of human ABCB1 revealed that multiple kinks are formed in the
      intracellular loop between transmembrane domains 10 and 11 of the A893P variant
      (2677G > C) protein. The polymorphisms of 2677G, 2677T, and 2677A exhibit wide
      ethnic differences in the allele frequency, and these nonsynonymous polymorphisms
      are suggested to be clinically important because of their altered ATPase activity
      and substrate specificity toward different drugs.

PMID- 17559194
TI  - pH dependent competition between Y(Z) and Y(D) in photosystem II probed by
      illumination at 5 K.
AB  - The photosystem II (PSII) reaction center contains two redox active tyrosines, YZ
      and YD, situated on the D1 and D2 proteins, respectively. By illumination at 5 K,
      oxidation of YZ in oxygen-evolving PSII can be observed as induction of the Split
      S1 EPR signal from YZ* in magnetic interaction with the CaMn4 cluster, whereas
      oxidation of YD can be observed as the formation of the free radical EPR signal
      from YD*. We have followed the light induced induction at 5 K of the Split S1
      signal between pH 4-8.5. The formation of the signal, that is, the oxidation of
      YZ, is pH independent and efficient between pH 5.5 and 8.5. At low pH, the split
      signal formation decreases with pKa approximately 4.7-4.9. In samples with
      chemically pre-reduced YD, the pH dependent competition between YZ and YD was
      studied. Only YZ was oxidized below pH 7.2, but at pH above 7.2, the oxidation of
      YD became possible, and the formation of the Split S1 signal diminished. The
      onset of YD oxidation occurred with pKa approximately 8.0, while the Split S1
      signal decreased with pKa approximately 7.9 demonstrating that the two tyrosines
      compete in this pH interval. The results reflect the formation and breaking of
      hydrogen bonds between YZ and D1-His190 (HisZ) and YD and D2-His190 (HisD),
      respectively. The oxidation of respective tyrosine at 5 K demands that the
      hydrogen bond is well-defined; otherwise, the low-temperature oxidation is not
      possible. The results are discussed in the framework of recent literature data
      and with respect to the different oxidation kinetics of YZ and YD.

PMID- 17559196
TI  - Intramolecular proton-transfer processes starting at higher excited states: a
      fluorescence study on 2-butylamino-6-methyl-4-nitropyridine N-oxide in nonpolar
      solutions.
AB  - This article describes the exceptional photophysics of 2-butylamino-6-methyl-4
      nitropyridine N-oxide (2B6M). It is known from the literature that this compound
      may undergo excited-state intra- or intermolecular proton-transfer reactions. In
      nonpolar solvents, 2B6M exhibits an unusual fluorescence behavior: there is a
      substantial difference between the relative band intensities of the excitation
      and absorption spectra. Furthermore, in emission two bands are observed, and
      their relative intensities depend on the excitation wavelength, thus violating
      the Kasha-Vavilov rule. It is the objective of this research to interpret these
      results. For this purpose, steady-state fluorescence excitation and emission
      spectra in the liquid state were recorded and quantum yields were determined for
      the two types of emission. In addition, absorption spectra were measured at room
      temperature and under low-temperature conditions. Finally, fluorescence lifetimes
      of the emitting species were determined using the time-correlated single photon
      counting technique. The results suggest that in the liquid state only one
      (monomeric) ground state species dominates, which can emit via two different
      pathways (from the normal and the tautomeric excited state). The excitation
      spectra point at two different internal proton-transfer processes, one starting
      at the S1 state and one starting at the S2 state. On the basis of the measured
      lifetimes and fluorescence quantum yields, a kinetic scheme was completed that
      can quantitatively explain the observations.

PMID- 17559195
TI  - Synthesis and characterization of allosteric probes of substrate channeling in
      the tryptophan synthase bienzyme complex.
AB  - Allosteric interactions regulate substrate channeling in Salmonella typhimurium
      tryptophan synthase. The channeling of indole between the alpha- and beta-sites
      via the interconnecting 25 A tunnel is regulated by allosteric signaling arising
      from binding of ligand to the alpha-site, and covalent reaction of l-Ser at the
      beta-site. This signaling switches the alpha- and beta-subunits between open
      conformations of low activity and closed conformations of high activity. Our
      objective is to synthesize and characterize new classes of alpha-site ligands
      (ASLs) that mimic the binding of substrates, 3-indole-d-glycerol 3'-phosphate
      (IGP) or d-glyceraldehyde 3-phosphate (G3P), for use in the investigation of
      alpha-site-beta-site interactions. The new synthesized IGP analogues contain an
      aryl group linked to an O-phosphoethanolamine moiety through amide, sulfonamide,
      or thiourea groups. The G3P analogue, thiophosphoglycolohydroxamate, contains a
      hydroxamic acid group linked to a thiophosphate moiety. Crystal structures of the
      internal aldimine complexed with G3P and with three of the new ASLs are
      presented. These structural and solution studies of the ASL complexes with the
      internal aldimine form of the enzyme establish the following. (1) ASL binding
      occurs with high specificity and relatively high affinities at the alpha-site.
      (2) Binding of the new ASLs slows the entry of indole analogues into the beta
      site by blocking the tunnel opening at the alpha-site. (3) ASL binding stabilizes
      the closed conformations of the beta-subunit for the alpha-aminoacrylate and
      quinonoid forms of the enzyme. (4) The new ASLs exhibit allosteric properties
      that parallel the behaviors of IGP and G3P.

PMID- 17559197
TI  - Molecular dynamics investigation into the structural features and transport
      properties of C60 in liquid argon.
AB  - Molecular dynamics (MD) simulations were performed to investigate the structural
      features and transport properties of C60 in liquid argon. The results reveal that
      an organized structure shell of liquid argon is formed close to the surface of a
      C60 fullerene molecule, thereby changing the solid/liquid interfacial structure.
      Furthermore, the simulation indicates that the C60-liquid argon fluid becomes
      structurally more stable as the C60 molecule volume fraction and the temperature
      increase. The viscosity of the fluid increases significantly as the C60 molecule
      loading is increased, particularly at a lower temperature. The thermal
      conductivity enhancement of the fluid in the present simulations is anomalously
      an order of magnitude higher than the theoretical predictions from either the
      Maxwell or the Lu and Liu models, and is found to vary approximately linearly
      with the C60 molecule volume fraction. The increased thermal conductivity is
      attributed to the nature of heat conduction in C60 molecule suspensions and an
      organized structure at the solid/liquid interface.

PMID- 17559193
TI  - Assembly and trafficking of heterotrimeric G proteins.
AB  - To be activated by cell surface G protein-coupled receptors, heterotrimeric G
      proteins must localize at the cytoplasmic surface of plasma membranes. Moreover,
      some G protein subunits are able to traffic reversibly from the plasma membrane
      to intracellular locations upon activation. This current topic will highlight new
      insights into how nascent G protein subunits are assembled and how they arrive at
      plasma membranes. In addition, recent reports have increased our knowledge of
      activation-induced trafficking of G proteins. Understanding G protein assembly
      and trafficking will lead to a greater understanding of novel ways that cells
      regulate G protein signaling.

PMID- 17559198
TI  - Determination of the formation of dark state via depleted spontaneous emission in
      a complex solvated molecule.
AB  - We present a general two-color two-pulse femtosecond pump-dump approach to study
      the specific population transfer along the reaction coordinate through the higher
      vibrational energy levels of excited states of a complex solvated molecule via
      the depleted spontaneous emission. The time-dependent fluorescence depletion
      provides the correlated dynamical information between the monitored fluorescence
      state and the SEP "dumped" dark states, and therefore allow us to obtain the
      dynamics of the formation of the dark states corresponding to the ultrafast
      photoisomerization processes. The excited-state dynamics of LDS 751 have been
      investigated as a function of solvent viscosity and solvent polarity, where a
      cooperative two-step isomerization process is clearly identified within LDS 751
      upon excitation.

PMID- 17559199
TI  - Photophysical properties of photoactive molecules with conjugated push-pull
      structures.
AB  - The photophysical properties of two newly synthesized photoactive compounds with
      asymmetrical D-pi-A structure and symmetrical D-pi-A-pi-D structure are
      investigated in different aprotic solvents by steady-state and femtosecond
      fluorescence depletion measurements. It is found that the asymmetrical DA
      compound has larger dipole moment change than that of the symmetrical DAD
      compound upon excitation, where the dipole moments of the two compounds have been
      estimated using the Lippert-Mataga equation. Furthermore, the steady-state
      spectral results show that increasing solvent polarity results in small
      solvatochromic shift in the absorption maxima but a large red shift in the
      fluorescence maxima for them, indicating that the dipole moment changes mainly
      reflect the changes of dipole moment in excited-state rather than in ground
      state. The red-shifted fluorescence band is attributed to an intramolecular
      charge transfer (ICT) state upon photoexcitation, which could result in a strong
      interaction with the surrounding solvents to cause the fast solvent
      reorganization. The resulting ICT states of symmetrical compounds are less polar
      than the asymmetrical compounds, indicating the different extents of
      stabilization of solute-solvent interaction in the excited state. Femtosecond
      fluorescence depletion measurements are further employed to investigate the fast
      solvation effects and dynamics of the ICT state of these two novel compounds. The
      femtosecond fluorescence depletion results show that the DA compound has faster
      solvation time than that of DAD compound, which corresponds to the formation of
      relaxed ICT state (i.e., a final ICT state with rearranged solvent molecules
      after solvation) in polar solvents. It is therefore reasonably understood that
      the ICT compounds with asymmetrical (D-pi-A) structure have better performance
      for those photovoltaic devices, which strongly rely on the nature of the electron
      push-pull ability, compared to those symmetrical compounds (D-pi-A-pi-D).

PMID- 17559200
TI  - Electronic structure of some substituted iron(II) porphyrins. Are they
      intermediate or high spin?
AB  - The electronic structure of some substituted, four-coordinate iron(II) porphyrins
      has been investigated with DFT methods. These systems include iron
      tetraphenylporphine (FeTPP), iron octamethyltetrabenzporphine (FeOTBP), iron
      tetra(alpha,alpha,alpha,alpha-orthopivalamide)phenylporphine (FeTpivPP, also
      called "picket fence" porphyrin), halogenated iron porphyrins (FeTPPXn, X=F, Cl;
      n=20, 28), and iron octaethylporphine (FeOEP). A number of density functionals
      were used in the calculations. Different from the popular, intermediate-spin
      FeTPP, the ground states of FeOTBP, FeTPPCl28, and FeTPPF20betaCl8 are predicted
      to be high spin. The calculated result for FeOTBP is in agreement with the early
      experimental measurement, thereby changing the previous conclusion drawn from the
      calculations with only the BP functional (J. Chem. Phys. 2002, 116, 3635). But
      FeTpivPP might have an intermediate-spin ground state, a conclusion that is
      different from the "experimental" one. With a notably expanded Fe-N bond length,
      FeOEP might exist as an admixed-spin (S=1, 2) state. We also calculated the
      electron affinities (EAs) for the various iron porphyrins and compared them to
      experiment. On the basis of the calculated trends in the EAs and in the orbital
      energies, the experimental EAs for FeTpivPP, FeTPPF20, and FeTPPCl28 may be too
      small by 0.4-0.5 eV.

PMID- 17559201
TI  - Hydration energies of sodiated amino acids from gas-phase equilibria
      determinations.
AB  - The sequential hydration of a number of sodiated amino acids is investigated
      using a high-pressure mass spectrometer. Ions produced continuously by
      electrospray are injected into the reaction chamber in the pulsed mode where the
      hydration equilibria, AANa+(H2O)n-1+H2O=AANa+(H2O)n (AA=Val, Pro, Met, Phe, and
      Gln), and the temperature dependence of the equilibrium constants are measured in
      the gas phase at 10 mbar (N2 bath gas and known pressure of H2O). The
      thermochemical properties, DeltaH degrees n, DeltaS degrees n, and DeltaG degrees
      n, for the hydrated systems are determined and discussed in conjunction with the
      structural forms. The results show that the binding energies of water to the
      AANa+ complexes decrease with the increasing number of water molecules. The
      present results from equilibrium measurements are compared to those from earlier
      studies obtained by other techniques. A correlation between the free energy
      changes for the addition of the first and second water molecules to AANa+, and
      the corresponding sodium ion affinities, is observed. Generally, the hydration
      free energy becomes weaker as the AA-Na+ bond strength increases.

PMID- 17559202
TI  - Carbocation branching observed in a simulation.
AB  - We have observed the branching rearrangement of a straight-chain secondary
      carbocation (C9H19+) in an ab initio molecular dynamics (AIMD) reverse-annealing
      (rising-temperature) simulation. The mechanism observed is one involving closed
      (protonated-cyclopropane) structures, previously observed in traditional geometry
      optimization calculations. However, the simulations give us a better
      understanding of the dynamics involved, leading to two advances: a simpler
      description of carbenium ion structures in general and the discovery of important
      entropy effects.

PMID- 17559203
TI  - Structure-activity relationships of alpha-ketooxazole inhibitors of fatty acid
      amide hydrolase.
AB  - A systematic study of the structure-activity relationships of 2b (OL-135), a
      potent inhibitor of fatty acid amide hydrolase (FAAH), is detailed targeting the
      C2 acyl side chain. A series of aryl replacements or substituents for the
      terminal phenyl group provided effective inhibitors (e.g., 5c, aryl = 1-napthyl,
      Ki = 2.6 nM), with 5hh (aryl = 3-ClPh, Ki = 900 pM) being 5-fold more potent than
      2b. Conformationally restricted C2 side chains were examined, and many provided
      exceptionally potent inhibitors, of which 11j (ethylbiphenyl side chain) was
      established to be a 750 pM inhibitor. A systematic series of heteroatoms (O, NMe,
      S), electron-withdrawing groups (SO, SO2), and amides positioned within and
      hydroxyl substitutions on the linking side chain were investigated, which
      typically led to a loss in potency. The most tolerant positions provided
      effective inhibitors (12p, 6-position S, Ki = 3 nM, or 13d, 2-position OH, Ki = 8
      nM) comparable in potency to 2b. Proteome-wide screening of selected inhibitors
      from the systematic series of >100 candidates prepared revealed that they are
      selective for FAAH over all other mammalian serine proteases.

PMID- 17559204
TI  - Inhibition of recombinant cytochrome P450 isoforms 2D6 and 2C9 by diverse drug
      like molecules.
AB  - The affinities of a diverse set of 500 drug-like molecules to cytochrome P450
      isoforms 2C9 and 2D6 were measured using recombinant expressed enzyme. The dose
      response curve of each compound was fitted with a series of equations
      representing typical or various types of atypical kinetics. Atypical kinetics was
      identified where the Akaike Information Criterion, plus other criteria, suggested
      the kinetics was more complex than expected for a Michaelis-Menten model.
      Approximately 20% of the compounds were excluded due to poor solubility, and
      approximately 15% were excluded due to fluorescence interference. Of the
      remaining compounds, roughly half were observed to bind with an affinity of 200
      microM or lower for each of the two isoforms. Atypical kinetics was observed in
      18% of the compounds that bind to cytochrome 2C9, but less than 2% for 2D6. The
      resulting collection of competitive inhibitors and inactive compounds were
      analyzed for trends in binding affinity. For CYP2D6, a clear relationship between
      polar surface area and charge was observed, with the most potent inhibitors
      having a formal positive charge and a low percent polar surface area. For CYP2C9,
      no clear trend between activity and physicochemical properties could be seen for
      the group as a whole; however, certain classes of compounds have altered
      frequencies of activity and atypical kinetics.

PMID- 17559205
TI  - Substituted E-3-(2-chloro-3-indolylmethylene)1,3-dihydroindol-2-ones with
      antitumor activity. Effect on the cell cycle and apoptosis.
AB  - The synthesis and antitumor activity of new E-3-(2-chloro-3-indolylmethylene)1,3
      dihydroindol-2-ones is described. They were studied at the National Cancer
      Institute, taking into consideration the 50% growth inhibitory power (pGI50), the
      cytostatic effect (pTGI = total growth inhibition), and the cytotoxic effect
      (pLC50). All the compounds were potent growth inhibitors, with mean pGI50 ranging
      from 5.26 to 7.72. They were also analyzed with NCI COMPARE algorithm. Further
      studies were dedicated to the effects on the cell cycle and apoptosis.

PMID- 17559206
TI  - New sst4/5-selective somatostatin peptidomimetics based on a constrained
      tryptophan scaffold.
AB  - The synthesis and biological evaluation of four peptidomimetic analogs of
      somatostatin based on a constrained Trp residue, 3-amino-indolo[2,3-c]azepin-2
      one (Aia), are reported. It is shown that dipeptidomimetics with a D-Aia-Lys
      sequence, functionalized with N- and C-terminal aromatic substituents, display a
      good selectivity for both sst4 and sst5. This study allowed us to identify a new
      highly potent sst5 agonist with good selectivity over the other receptors, except
      versus sst4.

PMID- 17559207
TI  - A multivariate approach to investigate docking parameters' effects on docking
      performance.
AB  - Increasingly powerful docking programs for analyzing and estimating the strength
      of protein-ligand interactions have been developed in recent decades, and they
      are now valuable tools in drug discovery. Software used to perform dockings
      relies on a number of parameters that affect various steps in the docking
      procedure. However, identifying the best choices of the settings for these
      parameters is often challenging. Therefore, the settings of the parameters are
      quite often left at their default values, even though scientists with long
      experience with a specific docking tool know that modifying certain parameters
      can improve the results. In the study presented here, we have used statistical
      experimental design and subsequent regression based on root-mean-square deviation
      values using partial least-square projections to latent structures (PLS) to
      scrutinize the effects of different parameters on the docking performance of two
      software packages: FRED and GOLD. Protein-ligand complexes with a high level of
      ligand diversity were selected from the PDBbind database for the study, using
      principal component analysis based on 1D and 2D descriptors, and space-filling
      design. The PLS models showed quantitative relationships between the docking
      parameters and the ability of the programs to reproduce the ligand
      crystallographic conformation. The PLS models also revealed which of the
      parameters and what parameter settings were important for the docking performance
      of the two programs. Furthermore, the variation in docking results obtained with
      specific parameter settings for different protein-ligand complexes in the diverse
      set examined indicates that there is great potential for optimizing the parameter
      settings for selected sets of proteins.

PMID- 17559208
TI  - Interaction between metal nitrates and carbohydrates: the topology coordination
      behavior of galactitol with trivalent lanthanide and divalent alkaline earth
      ions.
AB  - It has long been known that metal ions and saccharides are involved in many
      biochemical processes. In this paper, metal nitrates were used as reactants to
      detect the coordination structures of the hydroxyl groups of galactitol in
      different environments. Three novel crystal structures and FT-IR spectra of metal
      nitrate-galactitol complexes of La(NO3)3.C6H14O6.(4)H2O, 2Ca(NO3)2.C6H14O6.H2O,
      and Sr(NO3)2.C6H14O6 were examined in an effort to clarify the structural factors
      that control metal ion interactions with saccharides in aqueous and biological
      systems. The coordination structures of galactitol with alkaline earth and
      lanthanide nitrates in the solid state were compared using FT-IR, Raman, and X
      ray diffraction techniques to extensively discuss the coordination rules of
      different kinds of metal ions. Results provided a model of the coordination sites
      found in sugars and showed that the introduction of NO3- made the coordination
      modes of galactitol more diverse and complex than those of the corresponding
      chloride complexes. Specifically, new coordination modes of galactitol and
      complicated topology networks were found in 2Ca(NO3)2.C6H14O6.H2O and
      Sr(NO3)2.C6H14O6. FT-IR results are consistent with the crystal structures and
      thus provide the possibility of using the similarity of IR spectra to speculate
      about unknown structures when the compounds are difficult to prepare as single
      crystals.

PMID- 17559209
TI  - General sacrificial template method for the synthesis of cadmium chalcogenide
      hollow structures.
AB  - Semiconductor CdX (X=Te, Se, S) hollow structures have been successfully prepared
      by using Cd(OH)Cl precursors as a sacrificial template. The hollow structures can
      be hollow spheres or tubes by controlling the shape of the sacrificial template.
      The products were characterized by X-ray diffraction, transmission electron
      microscopy, scanning electron microscopy, and energy-dispersive spectrometry. The
      obtained results showed that the hollow structures had complementary shapes and
      sizes of the original sacrificial templates. This is a general method for the
      synthesis of cadmium chalcogenide hollow structures, and the method is simpler
      and more practical than direct synthesis of certain hollow structures, which
      further widens the avenue to using those materials that have been synthesized
      with various shapes to fabricate specific hollow structures.

PMID- 17559210
TI  - Phosphate-mediated molecular memory driven by two different protein kinases as
      information input elements.
AB  - There is increasing interest in studying molecular-based devices that perform
      Boolean logic operations whose output state (0 or 1) depends on the input
      conditions (0/0, 1/0, 0/1, or 1/1). So far, great efforts have been devoted to
      establish molecular-scaled logic gates activated by chemical, physical, and
      biological inputs. We herein describe the design and synthesis of a tandem
      protein kinase substrate peptide acting as a phosphate-mediated molecular memory.
      The molecular-based memory system is comprised of two different phosphorylatable
      substrate regions joined in series and a spiropyran derivative at the N-terminus.
      We also demonstrated three basic "AND", "OR", and "NOR" logic operations on the
      basis of alterations in the spiropyran-to-merocyanine (SP-to-MC) thermocoloration
      properties of the spiropyran moiety in the peptide upon kinase-catalyzed
      phosphorylation. The three logic functions were successfully performed by adding
      ionic polymers as programming elements with preset thresholds of a signal
      intensity in a microplate format. Throughout this study, information was recorded
      on the substrate peptide by protein kinase-catalyzed phosphorylation, stored
      stably as phosphoesters, read according to the extent of the SP-to-MC
      thermocoloration, and erased by phosphatase-catalyzed dephosphorylation,
      resulting in the peptide returning to the initial recordable state. Thus, the
      proof-of-concept experiments described herein could be used to provide clues for
      developing practical molecular-based processing and computing.

PMID- 17559211
TI  - Ultrafast nonadiabatic dynamics of [Fe(II)(bpy)(3)](2+) in solution.
AB  - The ultrafast relaxation of aqueous iron(II)-tris(bipyridine) upon excitation
      into the singlet metal-to-ligand charge-transfer band (1MLCT) has been
      characterized by femtosecond fluorescence up-conversion and transient absorption
      (TA) studies. The fluorescence experiment shows a very short-lived broad 1MLCT
      emission band at approximately 600 nm, which decays in < or =20 fs, and a weak
      emission at approximately 660 nm, which we attribute to the 3MLCT, populated by
      intersystem crossing (ISC) from the 1MLCT state. The TA studies show a short
      lived (<150 fs) excited-state absorption (ESA) below 400 nm, and a longer-lived
      one above 550 nm, along with the ground-state bleach (GSB). We identify the short
      lived ESA as being due to the 3MLCT state. The long-lived ESA decay and the GSB
      recovery occur on the time scale of the lowest excited high-spin quintet state
      5T2 lifetime. A singular value decomposition and a global analysis of the TA
      data, based on a sequential relaxation model, reveal three characteristic time
      scales: 120 fs, 960 fs, and 665 ps. The first is the decay of the 3MLCT, the
      second is identified as the population time of the 5T2 state, while the third is
      its decay time to the ground state. The anomalously high ISC rate is identical in
      [RuII(bpy)3]2+ and is therefore independent of the spin-orbit constant of the
      metal atom. To reconcile these rates with the regular quasi-harmonic vibrational
      progression of the 1MLCT absorption, we propose a simple model of avoided
      crossings between singlet and triplet potential curves, induced by the strong
      spin-orbit interaction. The subsequent relaxation steps down to the 5T2 state
      dissipate approximately 2000 cm-1/100 fs. This rate is discussed, and we conclude
      that it nevertheless can be described by the Fermi golden rule, despite its high
      value.

PMID- 17559212
TI  - Understanding d(0)-olefin metathesis catalysts: which metal, which ligands?
AB  - Density functional theory (DFT, B3PW91) calculations have been carried out on the
      reactivity of ethene with model systems M(NR)(=CHCH3)(X)(Y) for M = Mo or W, R =
      methyl or phenyl, X = CH2CH3, OCH3, or OSiH3, and Y = CH2CH3, OCH3, or OSiH3,
      which are representative of experimental olefin metathesis catalysts, and the
      results are compared to those previously obtained for Re(CCH3)(=CHCH3)(X)(Y). The
      general pathway comprises four steps: olefin coordination, [2+2] cycloaddition,
      cycloreversion, and olefin de-coordination. Two key factors have been found to
      control the detailed shape of the energy profiles: the energy of distortion of
      the tetrahedral catalyst and the stability of the metallacycle intermediate,
      which is controlled by the M-C bond strength. The efficiency has been evaluated
      by calculating the turnover frequency (TOF) based on the steady-state
      approximation, and the most striking feature is that the unsymmetrical catalysts
      (X not equal to Y) are systematically more efficient for all systems (Mo, W, and
      Re). Overall, the Re complexes have been found to be less efficient than the Mo
      and W catalysts, except when Re is unsymmetrically substituted: it is then
      calculated to be as efficient as the best Mo and W catalysts.

PMID- 17559213
TI  - Structural and co-conformational effects of alkyne-derived subunits in charged
      donor-acceptor [2]catenanes.
AB  - Four donor-acceptor [2]catenanes with cyclobis(paraquat-p-phenylene) (CBPQT4+) as
      the pi-electron-accepting cyclophane and 1,5-dioxynaphthalene (DNP)-containing
      macrocyclic polyethers as pi-electron donor rings have been synthesized under
      mild conditions, employing Cu+-catalyzed Huisgen 1,3-dipolar cycloaddition and
      Cu2+-mediated Eglinton coupling in the final steps of their syntheses. Oligoether
      chains carrying terminal alkynes or azides were used as the key structural
      features in template-directed cyclizations of [2]pseudorotaxanes to give the
      [2]catenanes. Both reactions proceed well with precursors of appropriate
      oligoether chain lengths but fail when there are only three oxygen atoms in the
      oligoether chains between the DNP units and the reactive functional groups. The
      solid-state structures of the donor-acceptor [2]catenanes confirm their
      mechanically interlocked nature, stabilized by [pi...pi], [C-H...pi], and [C
      H...Omicron] interactions, and point to secondary noncovalent contacts between
      1,3-butadiyne and 1,2,3-triazole subunits and one of the bipyridinum units of the
      CBPQT4+ ring. These contacts are characterized by the roughly parallel
      orientation of the inner bipyridinium ring system and the 1,2,3-triazole and 1,3
      butadiyne units, as well as by the short [pi...pi] distances of 3.50 and 3.60 A,
      respectively. Variable-temperature 1H NMR spectroscopy has been used to identify
      and quantify the barriers to the conformationally and co-conformationally dynamic
      processes. The former include the rotations of the phenylene and the bipyridinium
      ring systems around their substituent axes, whereas the latter are confined to
      the circumrotation of the CBPQT4+ ring around the DNP binding site. The barriers
      for the three processes were found to be successively 14.4, 14.5-17.5, and 13.1
      15.8 kcal mol-1. Within the limitations of the small dataset investigated,
      emergent trends in the barrier heights can be recognized: the values decrease
      with the increasing size of the pi-electron-donating macrocycle and tend to be
      lower in the sterically less encumbered series of [2]catenanes containing the 1,3
      butadiyne moiety.

PMID- 17559214
TI  - Oxepane nucleic acids: synthesis, characterization, and properties of
      oligonucleotides bearing a seven-membered carbohydrate ring.
AB  - The synthesis and properties of oxepane nucleic acids (ONAs) are described. ONAs
      are sugar-phosphate oligomers in which the pentofuranose ring of DNA and RNA is
      replaced with a seven-membered (oxepane) sugar ring. The oxepane nucleoside
      monomers were prepared from the ring expansion reaction of a cyclopropanated
      glycal, 1, and their conversion into phosphoramidite derivatives allowed
      efficient assembly of ONAs on a solid support. ONAs (oT15 and oA15) were found to
      be much more resistant toward nuclease degradation than natural DNA (dT15 and
      dA15) in fetal bovine serum (FBS) after 24 h of incubation at 37 degrees C. ONAs
      also display several attributes in common with the naturally occurring DNA. For
      example, oT15 exhibited cross-pairing with complementary RNA to give a duplex
      (oT15/rA15) whose conformation evaluated by CD spectroscopy very closely matched
      that of the natural DNA/RNA hybrid (dT15/rA15). Furthermore, oT15 was found to
      elicit Escherichia coli RNase H-mediated degradation of the rA15 strand. When we
      compared the rates of RNase H-mediated degradation induced by 5- (furanose,
      dT15), 6- (2'-enopyranose, pT18), and 7-membered (oxepane, oT15) ring
      oligonucleotides at a temperature that ensures maximum duplex population (10
      degrees C), the following trend was observed: dT15 >> oT15 > pT18. The wider
      implications of these results are discussed in the context of our current
      understanding of the catalytic mechanism of the enzyme. The homopolymer oT15 also
      paired with its oxepane complement, oA15, to form a duplex structure that was
      different [as assessed by circular dichroic (CD) spectroscopy] and of lower
      thermal stability relative to the native dT15/dA15 hybrid. Hence, ONAs are useful
      tools for biological studies and provide new insights into the structure and
      function of natural and alternative genetic systems.

PMID- 17559215
TI  - Structural characterization of quaterphenyl cation radical: X-ray
      crystallographic evidence of quinoidal charge delocalization in poly-p-phenylene
      cation radicals.

PMID- 17559216
TI  - Preference of 4-exo ring closure in copper-catalyzed intramolecular coupling of
      vinyl bromides with alcohols.

PMID- 17559217
TI  - Formation of benzo-fused carbocycles by formal radical cyclization onto an
      aromatic ring.
AB  - An indirect method for effecting radical carbocyclization onto aromatic rings is
      described. Cross-conjugated dienones such as 13, readily prepared by Birch
      reduction of aromatic tert-butyl esters, in situ alkylation, and oxidation (10 -
      > 11 --> 12 --> 13), undergo radical cyclization; the products (14) are
      aromatized by silylation, Saegusa oxidation, and treatment with BiCl3.H2O. A
      noteworthy feature of this route is that it provides opportunities to attach an
      additional substituent to the original aromatic ring.

PMID- 17559218
TI  - Modified chiral triazolium salts for enantioselective benzoin cyclization of
      enolizable keto-aldehydes: synthesis of (+)-sappanone B.
AB  - Asymmetric synthesis of (+)-sappanone B (1), a natural product with a 3-hydroxy
      chromanone structure, was achieved via enantioselective benzoin cyclization by
      using a modified Rovis catalyst and triethylamine. This catalyst enabled the
      successful benzoin cyclization of readily enolizable keto-aldehydes.

PMID- 17559219
TI  - Preparation and use of enantioenriched allenylsilanes for the stereoselective
      synthesis of homopropargylic ethers.
AB  - A convenient procedure for the synthesis of highly enantioenriched allenylsilanes
      by Johnson orthoester Claisen rearrangement of 1-silyl propargylic alcohols is
      described. Allenylsilanes are then used as carbon nucleophiles in three
      component, Lewis acid mediated additions to in situ generated oxonium ions,
      resulting in enantioenriched homopropargylic ethers.

PMID- 17559220
TI  - A cyclopropanol-based strategy for subunit coupling: total synthesis of (+)
      spirolaxine methyl ether.
AB  - A strategy for ketone synthesis with cyclopropanols as intermediates and its
      application to (+)-spirolaxine methyl ether is described. The synthesis also
      features an application of Fu's alkyl-alkyl Suzuki coupling.

PMID- 17559221
TI  - Electrophilicity and nucleophilicity index for radicals.
AB  - Radicals can be regarded as electrophilic/nucleophilic, depending on their
      tendency to attack sites of relatively higher/lower electron density. In this
      paper, an electrophilicity scale, global as well as local, and a nucleophilicity
      scale for 35 radicals is reported. The global electrophilicity scale correlates
      well with the nucleophilicity scale, suggesting that these concepts are inversely
      related.

PMID- 17559222
TI  - Inverse-electron-demand hetero-Diels-Alder reaction of beta,gamma-unsaturated
      alpha-ketophosphonates catalyzed by prolinal dithioacetals.
AB  - Some novel prolinal dithioacetal derivatives were studied as catalysts for the
      inverse-electron-demand hetero-Diels-Alder reaction of enolizable aldehydes and
      beta,gamma-unsaturated alpha-ketophosphonates. The corresponding 5,6-dihydro-4H
      pyran-2-ylphosphonates were obtained in good ee values (up to 94% ee).

PMID- 17559223
TI  - Reconciling icetexane biosynthetic connections with their chemical synthesis:
      total synthesis of (+/-)-5,6-dihydro-6alpha-hydroxysalviasperanol, (+/-)
      brussonol, and (+/-)-abrotanone.
AB  - A unified strategy for the chemical synthesis of the icetexane diterpenoids
      brussonol and 5,6-dihydro-6alpha-hydroxysalviasperanol has led to a structural
      revision of the recently isolated natural products abrotandiol and abrotanone.

PMID- 17559224
TI  - Effect of the interfacial layer composition on the properties of emulsion creams.
AB  - We have quantified observed differences in the microstructure and rheology of
      creaming emulsions stabilized by protein and low molecular weight surfactants. In
      this study, we made two sets of emulsions from a single parent emulsion, which
      differed only in their interfacial composition (i.e., either protein or
      surfactant). The protein studied was whey protein isolate. The zeta potential of
      the surfactant-stabilized emulsion was controlled by mixing anionic (SDS) and
      nonionic (Brij 35) surfactants to match the zeta potential of the protein
      stabilized emulsion. Despite this, ultrasonic creaming measurements and confocal
      microscopy showed that the structures within the cream layers were different
      between the two sets of emulsions. The protein-stabilized emulsions appeared to
      slow or arrest the packing within the cream, leading to a lower density network
      of emulsion droplets, whereas the surfactant emulsion droplets rearranged more
      quickly into a well-packed, concentrated cream layer. Rheological analysis of the
      creams showed that despite the protein-stabilized emulsions having a lower
      dispersed phase volume fraction, their elastic modulus was approximately 30 times
      greater than that of a comparable surfactant-stabilized emulsion. These
      differences were caused by the ability of the protein to form a highly
      viscoelastic interfacial network around the droplets which may include
      intermolecular covalent cross-links. At close range the adhesive nature of the
      interaction between the layers contributes to the microstructure and rheology of
      concentrated emulsions. This is the first time that such well-defined emulsion
      systems have been studied in detail both noninvasively to look at the impact on
      creaming and also invasively to look at the impact on bulk rheological
      properties.

PMID- 17559225
TI  - Metabolic protein patterns and monascorubrin production revealed through
      proteomic approach for Monascus pilosus treated with cycloheximide.
AB  - Monascus species have the unique ability to economically produce many secondary
      metabolites. However, most metabolic regulation processes in the production of
      secondary metabolites in Monascus remain unclear. We found that the translational
      inhibitor cycloheximide induced different expression patterns between the
      monascorubrin pigment production and the growth in Monascus pilosus. Here, we
      used the proteomic approach of two-dimensional gel electrophoresis, matrix
      assisted laser desorption ionization time-of-flight/time-of-flight liquid
      chromatography-mass spectrometry (MALDI-TOF/TOF LC-MS), and tandem mass
      spectrometry (MS/MS) to identify the intracellular and mitochondrial proteins of
      M. pilosus between the cycloheximide treatment and the control. These results
      revealed that the cycloheximide-induced down-regulated proteins were involved in
      transcriptional regulation, peptide synthesis, and other metabolic processes,
      such as methylation of secondary metabolites. In contrast, the energy-related
      proteins, such as the transcriptional regulator rosAr and 1,4-alpha-glucan
      branching enzyme, were up-regulated as compared to the control.

PMID- 17559226
TI  - An exploratory study of the nutritional composition of Tanoak (Lithocarpus
      densiflorus) acorns after potassium phosphonate treatment.
AB  - Native American Pomo communities who live in the Northern Coastal range of
      California and consume acorns from tanoak trees as part of traditional diets are
      facing the potential loss of many culturally important trees to sudden oak death.
      Pomo and other Native American communities are reluctant to use the protective
      fungicide, potassium phosphonate, on trees used for acorn collection without
      information on how the treatment affects acorn properties. In this study, select
      macronutrients and polyphenolics were quantified in tanoak acorns to evaluate the
      influence of potassium phosphonate treatment on the composition and nutritional
      value of tanoak acorns. Of the fatty acids tested from C14:0 to C20:1, only C17:0
      was significantly lower (p < 0.05) in the nontreated and treated acorns after the
      first year. There were no differences detected in total phenolic content, gallic
      acid content, or ellagic acid content. Protein, phosphorus, and potassium levels
      were not significantly affected by fungicide treatment. Soluble glucose and
      fructose levels were significantly higher (p < 0.05) in both nontreated and
      treated groups after the first year; soluble sucrose levels did not change. Total
      glucose, starch, and total nonstructural carbohydrates increased significantly (p
      < 0.05) in the nontreated group after the first year but not in the treatment
      group; however, the treatment group values did not differ significantly from the
      control group values at baseline. The lack of any negative significant
      differences between acorns from treated and untreated tanoak trees implies that
      sodium phosphonate application for the prevention of sudden oak death does not
      impact the predominant polyphenolics or macronutrient quality of tanoak acorns.

PMID- 17559227
TI  - Event-specific detection of seven genetically modified soybean and maizes using
      multiplex-PCR coupled with oligonucleotide microarray.
AB  - With the increasing development of genetically modified organism (GMO) detection
      techniques, the polymerase chain reaction (PCR) technique has been the mainstay
      for GMO detection. An oligonucleotide microarray is a glass chip to the surface
      of which an array of oligonucleotides was fixed as spots, each containing
      numerous copies of a sequence-specific probe that is complementary to a gene of
      interest. So it is used to detect ten or more targets synchronously. In this
      research, an event-specific detection strategy based on the unique and specific
      integration junction sequences between the host plant genome DNA and the
      integrated gene is being developed for its high specificity using multiplex-PCR
      together with oligonucleotide microarray. A commercial GM soybean (GTS 40-3-2)
      and six GM maize events (MON810, MON863, Bt176, Bt11, GA21, and T25) were
      detected by this method. The results indicate that it is a suitable method for
      the identification of these GM soybean and maizes.

PMID- 17559228
TI  - Isolation, characterization, and emulsifying properties of wattle seed (Acacia
      victoriae Bentham) extracts.
AB  - Extracts from either ground whole wattle seeds or uncoated cotyledons were
      obtained using water, alkali, or ethanol. These extracts were then analyzed for
      their protein molecular weight and electrophoretic profiles using sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis and capillary electrophoresis,
      respectively. Water extracts and those from the cotyledons gave higher material
      yield and contained significantly more proteins than other extracts. Furthermore,
      the proteins ranged in molecular weight from 6 to 92 kDa, with the highest
      concentration between 27 and 61 kDa. Water extracts, even at very low protein
      concentrations (0.17-1.12%), formed stable emulsions, containing up to 50% canola
      oil, and these emulsions were affected by pH (4-9), ionic strength (0.25-1%
      NaCl), and retorting (115 degrees C for 30 min). The study showed that water
      soluble wattle extracts have great potential as emulsifiers and stabilizers for
      the food industry, especially at low pH levels.

PMID- 17559229
TI  - Electron transfer reaction mechanism of cisplatin with DNA at the molecular
      level.
AB  - The cytotoxicity of cisplatin as a very effective chemotherapeutic anticancer
      drug is known to arise from its capacity to damage DNA. However, the mechanism of
      action of cisplatin at the molecular level, in particular, the reaction dynamics
      of cisplatin with DNA, remains elusive, and the reason why cisplatin binds to the
      guanine bases rather than to S-donor ligands available in cells remains a
      mystery. Using time-resolved femtosecond laser spectroscopy, for the first time,
      we reveal the high reactivity of cisplatin with electrons and its preferential
      electron-transfer reaction with the DNA guanine base. The results not only
      provide a molecular mechanistic understanding of cisplatin in cancer therapy but
      may have far-reaching significance for understanding the role of polar molecules
      such as NH3 and NH2 in biological reactions.

PMID- 17559230
TI  - Polymer selection for biphenyl degradation in a solid-liquid two-phase
      partitioning bioreactor.
AB  - The commercially available thermoplastic polymer Hytrel was selected as the
      delivery phase for the hydrophobic model compound biphenyl in a solid-liquid two
      phase partitioning bioreactor (TPPB), and 2.9 g biphenyl could successfully be
      degraded in 1-L TPPBs by a pure culture of the biphenyl-degrading bacterium
      Burkholderia xenovorans LB400 in 50 h and by a mixed microbial consortium
      isolated from contaminated soil in 45 h. TPPBs consist of an aqueous cell
      containing phase and an immiscible second phase that partitions toxic and/or
      poorly soluble substrates (in this case biphenyl) on the basis of maintaining a
      thermodynamic equilibrium. This paper illustrates a rational strategy for
      selecting a suitable solid polymeric substance for the delivery of the poorly
      water-soluble model compound biphenyl. The partitioning of biphenyl between the
      selected polymers and water was analogous to partitioning of solutes between two
      immiscible liquid phases. The partitioning coefficients varied between 180 for
      Nylon 6.6 and 11,000 for Desmopan, where the later numerical value is comparable
      to biphenyl partitioning coefficients between water and organic solvents.
      Employing a solid delivery phase enabled the utilization of a surfactant
      producing microbial mixed culture, which could not be cultivated in liquid-liquid
      TPPBs and thereby extended the range of biocatalysts that can be employed in
      TPPBs.

PMID- 17559231
TI  - Allosteric regulation of tryptophan synthase channeling: the internal aldimine
      probed by trans-3-indole-3'-acrylate binding.
AB  - Substrate channeling in the tryptophan synthase bienzyme complex from Salmonella
      typhimurium is regulated by allosteric interactions triggered by binding of
      ligand to the alpha-site and covalent reaction at the beta-site. These
      interactions switch the enzyme between low-activity forms with open conformations
      and high-activity forms with closed conformations. Previously, allosteric
      interactions have been demonstrated between the alpha-site and the external
      aldimine, alpha-aminoacrylate, and quinonoid forms of the beta-site. Here we
      employ the chromophoric l-Trp analogue, trans-3-indole-3'-acrylate (IA), and
      noncleavable alpha-site ligands (ASLs) to probe the allosteric properties of the
      internal aldimine, E(Ain). The ASLs studied are alpha-d,l-glycerol phosphate (GP)
      and d-glyceraldehyde 3-phosphate (G3P), and examples of two new classes of high
      affinity alpha-site ligands, N-(4'-trifluoromethoxybenzoyl)-2-aminoethyl
      phosphate (F6) and N-(4'-trifluoromethoxybenzenesulfonyl)-2-aminoethyl phosphate
      (F9), that were previously shown to bind to the alpha-site by optical
      spectroscopy and X-ray crystal structures [Ngo, H., Harris, R., Kimmich, N.,
      Casino, P., Niks, D., Blumenstein, L., Barends, T. R., Kulik, V., Weyand, M.,
      Schlichting, I., and Dunn, M. F. (2007) Synthesis and characterization of
      allosteric probes of substrate channeling in the tryptophan synthase bienzyme
      complex, Biochemistry 46, 7713-7727]. The binding of IA to the beta-site is
      stimulated by the binding of GP, G3P, F6, or F9 to the alpha-site. The binding of
      ASLs was found to increase the affinity of the beta-site of E(Ain) for IA by 4-5
      fold, demonstrating for the first time that the beta-subunit of the E(Ain)
      species undergoes a switching between low- and high-affinity states in response
      to the binding of ASLs.

PMID- 17559232
TI  - Allosteric regulation of substrate channeling in tryptophan synthase: modulation
      of the L-serine reaction in stage I of the beta-reaction by alpha-site ligands.
AB  - In the tryptophan synthase bienzyme complex, indole produced by substrate
      cleavage at the alpha-site is channeled to the beta-site via a 25 A long tunnel.
      Within the beta-site, indole and l-Ser react with pyridoxal 5'-phosphate in a two
      stage reaction to give l-Trp. In stage I, l-Ser forms an external aldimine,
      E(Aex1), which converts to the alpha-aminoacrylate aldimine, E(A-A). Formation of
      E(A-A) at the beta-site activates the alpha-site >30-fold. In stage II, indole
      reacts with E(A-A) to give l-Trp. The binding of alpha-site ligands (ASLs) exerts
      strong allosteric effects on the reaction of substrates at the beta-site: the
      distribution of intermediates formed in stage I is shifted in favor of E(A-A),
      and the binding of ASLs triggers a conformational change in the beta-site to a
      state with an increased affinity for l-Ser. Here, we compare the behavior of new
      ASLs as allosteric effectors of stage I with the behavior of the natural product,
      d-glyceraldehyde 3-phosphate. Rapid kinetics and kinetic isotope effects show
      these ASLs bind with affinities ranging from micro- to millimolar, and the rate
      determining step for conversion of E(Aex1) to E(A-A) is increased by 8-10-fold.
      To derive a structure-based mechanism for stage I, X-ray structures of both the
      E(Aex1) and E(A-A) states complexed with the different ASLs were determined and
      compared with structures of the ASL complexes with the internal aldimine [Ngo,
      H., Harris, R., Kimmich, N., Casino, P., Niks, D., Blumenstein, L., Barends, T.
      R., Kulik, V., Weyand, M., Schlichting, I., and Dunn, M. F. (2007) Biochemistry
      46, 7713-7727].

PMID- 17559233
TI  - Proteomic analysis of in vivo 14-3-3 interactions in the yeast Saccharomyces
      cerevisiae.
AB  - The yeast Saccharomyces cerevisiae produces two 14-3-3 proteins, Bmh1 and Bmh2,
      whose exact functions have remained unclear. Here, we performed a comprehensive
      proteomic analysis using multistep immunoaffinity purification and mass
      spectrometry and identified 271 yeast proteins that specifically bind to Bmh1 and
      -2 in a phosphorylation-dependent manner. The identified proteins have diverse
      biochemical functions and cellular roles, including cell signaling, metabolism,
      and cell cycle regulation. Importantly, there are a number of protein subsets
      that are involved in the regulation of yeast physiology through a variety of cell
      signaling pathways, including stress-induced transcription, cell division, and
      chitin synthesis at the cell wall. In fact, we found that a yeast mutant
      deficient in Bmh1 and -2 had defects in signal-dependent response of the MAPK
      (Hog1 and Mpk1) cascade and exhibited an abnormal accumulation of chitin at the
      bud neck. We propose that Bmh1 and -2 are common regulators of many cell
      signaling modules and pathways mediated by protein phosphorylation and regulate a
      variety of biological events by coordinately controlling the identified multiplex
      phosphoprotein components.

PMID- 17559234
TI  - Quantitation of acrolein-derived (3-hydroxypropyl)mercapturic acid in human urine
      by liquid chromatography-atmospheric pressure chemical ionization tandem mass
      spectrometry: effects of cigarette smoking.
AB  - Recently published data suggest that acrolein (1), a toxic but weakly
      carcinogenic constituent of cigarette smoke, may be involved as a causative
      factor for the mutations frequently observed in the p53 tumor suppressor gene in
      lung cancer in smokers. Biomarkers are needed to further assess the possible
      relationship between acrolein uptake and cancer. In this study, we analyzed (3
      hydroxypropyl)mercapturic acid (3-HPMA, 2) in human urine. 3-HPMA is a major
      metabolite of acrolein in laboratory animals. The method employs [13C3]3-HPMA as
      an internal standard, with analysis and quantitation by LC-APCI-MS/MS-SRM. Clean,
      readily quantifiable chromatograms were obtained. The method was accurate and
      precise and required only 0.1 mL of urine. Median levels of 3-HPMA were
      significantly higher (2900 pmol/mg of creatinine, N=35) in smokers than in
      nonsmokers (683 pmol/mg of creatinine, N=21) (P=0.0002). The effect of smoking
      was further assessed by determining the levels of 3-HPMA before and after a 4
      week smoking cessation period. There was a significant 78% decrease in median
      levels of urinary 3-HPMA after cessation (P<0.0001). The relationship between the
      levels of urinary 3-HPMA and those of acrolein-derived 1,N2-propanodeoxyguanosine
      (PdG) adducts in lung was investigated in 14 smokers. There was a significant
      inverse relationship between urinary 3-HPMA and alpha-hydroxy-PdG (3) but not
      gamma-hydroxy-PdG (4) or total adduct levels. The results of this study clearly
      demonstrate that acrolein uptake in smokers is significantly higher than in
      nonsmokers and underline the need for further investigation of the possible
      relationship of acrolein uptake to lung cancer.

PMID- 17559235
TI  - Detection, characterization, and decay kinetics of ROS and thiyl adducts of mito
      DEPMPO spin trap.
AB  - We report here the detection and characterization of spin adducts formed from the
      trapping of reactive oxygen species (superoxide and hydroxyl radicals) and
      glutathiyl and carbon-centered radicals by a newly synthesized nitrone, Mito
      DEPMPO. This is a cationic nitrone spin trap with a triphenyl phosphonium cation
      conjugated to the DEPMPO analogue. The Mito-DEPMPO-OOH adduct, formed from the
      trapping of superoxide by Mito-DEPMPO, was enzymatically generated using
      xanthine/xanthine oxidase and neuronal nitric oxide synthase, and chemically
      generated by KO2 in 18-crown-6. The Mito-DEPMPO-OOH adduct exhibits an eight-line
      EPR spectrum with partial asymmetry arising from the alternate line-width effect.
      The half-life of the Mito-DEPMPO-OOH adduct is 2-2.5-times greater than that of
      the DEPMPO-OOH. The Mito-DEPMPO-SG adduct, formed from the trapping of glutathiyl
      radicals by Mito-DEPMPO, is 3-times more persistent than the analogue DEPMPO-SG
      adduct. In this study, we describe the EPR characterization of spin adducts
      formed from Mito-DEPMPO. The EPR parameters of Mito-DEPMPO adducts are distinctly
      different and highly characteristic. The detection of superoxide from an intact
      mitochondrion was feasible with Mito-DEPMPO but not with DEPMPO. We conclude that
      Mito-DEPMPO nitrone and its analogues are more effective than most nitrone spin
      traps for trapping superoxide, hydroxyl, and thiyl radicals formed in biological
      systems, including mitochondria.

PMID- 17559236
TI  - In-situ infrared spectroscopy of buried organic monolayers: influence of the
      substrate on titanium reactivity with a Langmuir-Blodgett film.
AB  - The reactivity of metals vapor deposited onto organic monolayers has historically
      been correlated to the metal/terminal organic group chemistry. Here we
      demonstrate that the chemical composition of the substrate unexpectedly plays a
      significant role as well. In particular, the reactivity of evaporated titanium
      toward a cadmium stearate Langmuir-Blodgett (LB) film was found to depend on the
      substrate upon which the LB film was deposited. Infrared spectra taken in a
      modified ATR (Kretschmann) geometry with a thin Au substrate showed large changes
      in peak shape, peak position, and peak width in the C-H stretching region,
      indicating titanium penetration into the LB film and decomposition of the
      original well-packed monolayer structure. LB monolayers formed on a platinum
      oxide (PtO(x)) surface showed remarkably small changes after Ti deposition,
      indicating only a slight increase in disorder and no significant metal
      penetration into the film. Films on SiO2 substrates showed reactivity between
      that of Au and PtO(x). These differences in reactivity can be correlated
      primarily with the amount of available oxygen associated with each substrate,
      including surface oxide layers and water incorporated within the LB film.

PMID- 17559237
TI  - Adsorption of normal pentane on the surface of rutile. Experimental results and
      simulations.
AB  - Adsorption isotherms and differential heats of normal pentane adsorption on
      microcrystalline rutile were measured at 303 K. The heat of adsorption of n
      pentane on rutile at zero occupancy is 64 kJ/mol. The differential heats have
      three descending segments, corresponding to the adsorption of n-pentane on three
      types of surfaces. At low coverage (first segment), the adsorption is restricted
      to the rows A of the (110) faces along the 5-fold coordinatively unsaturated
      (cus) Ti(4+) ions with differential heat showing a linear decrease with
      increasing occupancy. The second segment is attributed to bonding with atoms of
      the rows along the remaining faces exposed, (101) and (100). The third segment is
      related to a multilayer adsorption. The mean molar adsorption entropy of n
      pentane is ca. -25 J/mol K less than the entropy of the bulk liquid, thus
      revealing a hindered state of motion of the n-pentane molecules on the surface of
      rutile. Simulations of the adsorption of n-pentane on the three most abundant
      crystallographic faces of rutile were also performed. The adsorption isotherm
      obtained from the combination of each face's isotherm weighted by the respective
      abundance was found to be in a good agreement with the experimental data. A
      structural characterization of n-pentane near the surface was also conducted, and
      it was found that the substrate, especially for the (110) face, strongly perturbs
      the distribution of n-pentane conformations, compared to those found for the gas
      phase. Adsorbed molecules are predominantly oriented with their long axes and
      their backbone zigzag planes parallel to the surface and are also characterized
      by fewer gauche conformations than observed in the bulk phase.

PMID- 17559238
TI  - Suppression of the reversible thermal behavior of the layered double hydroxide
      (LDH) of Mg with Al: stabilization of nanoparticulate oxides.
AB  - The layered double hydroxide of Mg with Al decomposes below 600 degrees C with
      the loss of nearly 48% mass, resulting in the formation of an oxide residue
      having the rock salt structure and nanoparticulate morphology. However, this
      product reconstructs back into the parent LDH, owing to its compositional and
      morphological metastability. The oxide can be kinetically stabilized within an
      amorphous phosphate network built up through an ex situ reaction with a suitable
      phosphate source such as (NH4)H2PO4. This oxide transforms into a
      thermodynamically more stable phase with a spinel structure on soaking in an
      aqueous medium. The oxide residue has a nanoparticulate morphology as revealed by
      the Scherrer broadening of the Bragg reflections as well as by electron
      microscopy. This work shows that the hydroxide reconstruction reaction and spinel
      formation are competing reactions. Suppression of the former catalyzes spinel
      formation as the excess free energy of the metastable oxide residue is unlocked
      to promote the diffusion of Mg2+ ions from octahedral to tetrahedral sites, which
      is the essential precondition to the formation of a normal spinel. This reaction
      taking place as it does at ambient temperature and in solution helps in the
      retention of a nanostructured morphology for the spinel. Another way of
      stabilizing the oxide is by incorporating the thermally stable borate anion into
      the LDH. This paves the way for an in situ reaction between the cations of the
      host LDH and the borate guest. The in situ reaction directly leads to the
      formation of an oxide with a spinel structure.

PMID- 17559239
TI  - Conjugated polyelectrolytes with pH-dependent conformations and optical
      properties.
AB  - We report here the synthesis and characterization of two new conjugated polymers:
      poly{2,5-bis[3-(N,N-diethylammonium acetate)-1-oxapropyl]-1,4-phenylenevinylene}
      (P1') and poly{2,5-bis[3-(N,N,N-triethylammonium bromide)-1-oxapropyl]-1,4
      phenylenevinylene} (P2). Both polymers exhibit unique pH-dependent optical
      properties in aqueous solution. These pH-dependent optical properties are
      attributed to the mutual electrostatic repulsions of positive charges pendent on
      the benzene rings. This electrostatic repulsion leads to an increased or
      decreased torsional angle in the conjugated backbone, thus affecting the
      effective conjugation length of these polymers. The UV-vis spectra of P1 in
      various pH solutions exhibit a near-isosbestic point, which indicates changes in
      the composition of the two distinct conformations (the charged and the neutral
      forms). The transition between the highly charged state and the neutral state was
      clearly observed in the UV-vis and photoluminescence studies on both P1 and P2.
      This transition is particularly sensitive in the pH range from 6.2 to 7.0, a
      range that would allow the detection of minor environmental changes. P2 has a
      quantum efficiency of 14% in water, which is considered to be relatively high
      among water-soluble PPVs.

PMID- 17559240
TI  - Large area, molecularly smooth (0.2 nm rms) gold films for surface forces and
      other studies.
AB  - Using large-area (cm2) single-crystal mica sheets as the templating substrate, we
      have created correspondingly large template-stripped (TS) gold films (thickness
      82 +/- 2 nm) that appear smooth to within 0.2 nm rms roughness over their entire
      area. These gold films, created without the use of any releasing solvent, are
      characterized using AFM, X-ray diffraction, multiple beam interferometric fringes
      of equal chromatic order (FECO), and contact angle measurements. Being
      molecularly smooth over large areas and (adjustably) semitransparent, these films
      are especially suitable for use in the surface force balance (SFB), as shown by
      measurements of the normal force (F) versus distance (D) profiles between such a
      flat gold surface and a bare mica surface in water. The F(D) profiles are in good
      agreement with DLVO theory down to molecular contact and indicate that the gold
      surface is negatively charged under water.

PMID- 17559241
TI  - Anchor-lipid monolayers at the air-water interface; prearranging of model
      membrane systems.
AB  - Model membrane systems are gaining more and more interest both for basic studies
      of membrane-related processes as well as for biotechnological applications.
      Several different model systems have been reported among which the tethered
      bilayer lipid membranes (tBLMs) form a very attractive and powerful architecture.
      In all the proposed architectures, a control of the lateral organization of the
      structures at a molecular level is of great importance for an optimized
      preparation. For tBLMs, a homogeneous and not too dense monolayer is required to
      allow for the functional incorporation of complex membrane proteins. We present
      here an alternative approach to the commonly used self-assembly preparation.
      Lipids are spread on the air-water interface of a Langmuir film balance and form
      a monomolecular film. This allows for a better control of the lateral pressure
      and distribution for subsequent transfer to solid substrates. In this paper, we
      describe the properties of the surface monolayer, in terms of surface pressure,
      structure of the lipid molecule, content of lipid mixtures, temperature, and
      relaxations features. It is shown that a complete mixing of anchor-lipids and
      free lipids can be achieved. Furthermore, an increase of the spacer lengths and a
      decrease of the temperature lead to more compact films. This approach is a first
      step toward the fully controlled assembly of a model membrane system.

PMID- 17559242
TI  - Self-assembly in mixed aqueous solutions of amphiphilic block copolymers and
      vesicle-forming surfactant.
AB  - The self-assembly behavior of mixed solutions consisting of poly(isoprene-b
      ethylene oxide) (IEO) copolymer micelles and vesicle-forming
      didodecyldimethylammonium bromide (DDAB) was investigated. Dynamic light
      scattering indicated the presence of two populations of nanoassemblies in the
      solutions. By aid of atomic force microscopy, the larger ones were identified as
      block copolymer modified surfactant vesicles (BCMSVs) and the smaller ones as
      surfactant-modified block copolymer micelles (SMBCMs). This identification is
      based on the amphiphilic character of the low and high molecular weight molecules
      and the notion that exchange of unimers of both types can take place between the
      initial nanoassemblies in aqueous solution. Electrophoretic light scattering
      experiments showed that the nanostructures carry positive charges originating
      from the surfactant. The sizes of the nanoassemblies depend on the relative
      concentrations of both components. The behavior of the mixed systems was also
      found to depend on block copolymer composition and temperature. Nanoassemblies of
      smaller sizes were formed at higher temperatures. BCMSVs and SMBCMs are
      thermosensitive, in contrast to the temperature stability of pure block copolymer
      micelles. On the other hand, BCMSVs showed lesser sensitivity to temperature
      increase compared to the pure DDAB vesicles. This indicates that incorporation of
      macromolecules into the DDAB bilayer increases the stability of the vesicles.

PMID- 17559243
TI  - Controlling the hydrophobicity of submicrometer silica spheres via surface
      modification for nanocomposite applications.
AB  - We control the hydrophobicity of submicrometer silica spheres by modifying their
      surface with -CH3, -CH=CH2, -(CH2)(2)CH3, -CH2(CH2)(4)CH2-, -C(6)H(5), 
      (CH2)(7)CH3, and -(CH2)(11)CH3 groups through a modified one-step process. The
      scanning electron microscopy (SEM), quasi-elastic light scattering (QELS), UV
      visible spectra, nitrogen sorption, and water vapor adsorption methods are used
      to characterize the particles. The SEM micrographs of the particles demonstrate
      that the modified particles are uniformly spherical, monodisperse, and well
      shaped with the particle size ranging from 130 to 149 nm depending on the
      modified organic groups. In aqueous solution, the particles modified with phenyl
      groups have an obvious UV absorption peak at around 210 nm, whereas the other
      modified particles and unmodified particles do not have any UV-visible absorption
      peaks. There exist obvious differences in the amount of water vapor adsorbed
      depending on the type of surface functional groups of the modified particles.
      Compared with the unmodified particles, the modified particles have a lower water
      vapor adsorption because of the improved hydrophobicity of the particle surface.
      As a potential application, we prepared polystyrene/SiO2 nanocomposites by
      blending polystyrene with the synthesized particles. Water contact angle
      measurements show that the surface of the composite prepared with the modified
      particles are more hydrophobic. Confocal microscopy demonstrates that the
      particles are less agglomerated in the nanocomposite as the particles become more
      hydrophobic. These comprehensive experimental results demonstrate that the
      hydrophobicity of the particles can be easily controlled by surface modification
      with different organosilanes through a modified one-step process.

PMID- 17559244
TI  - Investigating the thermodynamic causes behind the anomalously large shifts in pKa
      values of benzoic acid-modified graphite and glassy carbon surfaces.
AB  - The difference between the values of 4-carboxyphenyl groups, covalently attached
      to either graphite (BAcarbon) or glassy carbon (BA-GC) surfaces, and benzoic acid
      in solution is explored using potentiometric titration and cyclic voltammetry. In
      solution, benzoic acid has a pKa of 4.20 at 25 degrees C. However, the observed
      pKa value on the graphitic surfaces shows significant deviations, with BAcarbon
      exhibiting a large shift to higher pKa values (pKa = 6.45) in contrast to BA-GC,
      which is shifted to lower pKa values (pKa = 3.25). Potentiometric titrations at
      temperatures between 25 and 50 degrees C allowed us to determine the surface pKa
      of these materials at each temperature studied and hence to determine the
      enthalpy, entropy, and Gibbs' energy changes associated with the ionization of
      the carboxylic acid groups. It was found that the enthalpic contribution is
      negligible and that the changes in surface pKa values are entropically
      controlled. This suggests that solvent ordering/disordering around the interface
      strongly influences the observed pKa value, which then reflects the relative
      hydrophobicity/hydrophilicity of the different graphitic surfaces.

PMID- 17559245
TI  - Wetting of nanogrooved polymer surfaces.
AB  - Molecular dynamics simulations were used to study the wetting of nanogrooved PE
      and PVC polymer surfaces. The contact angles, equilibrium states, and equilibrium
      shapes of two nanosized water droplets were analyzed on surfaces with 1D-arranged
      periodic roughness of various dimensions. The composite solid-liquid contact,
      which is preferred in practical applications and in which a droplet rests on top
      of the surface asperities, was observed on the roughest PE surfaces, whereas
      water filled the similar but slightly deeper grooves on PVC surfaces. The
      transition from the wetted to composite contact regime occurred when the contact
      angle with a flat surface reached the value at which the apparent Wenzel and
      Cassie contact angles are equal. Droplets on grooved PE surfaces with the
      composite contact exhibited contact angles in agreement with Cassie's equation,
      but the increase in hydrophobicity on smoother surfaces with the wetted contact
      was less than expected from Wenzel's equation. The difference between the
      simulated and theoretical values decreased as the dimensions of the surface
      grooves increased. Only a slight increase or even a slight decrease in the
      contact angles was observed on the grooved PVC surfaces, owing to the less
      hydrophobic nature of the flat PVC surface. On both polymers, the nanodroplet
      assumed a spherical shape in the composite contact. Only minor anisotropy was
      observed in the wetted contact on PE surfaces, whereas even a highly anisotropic
      shape was seen on the grooved PVC surfaces. The contact angle in the direction of
      the grooves was smaller than that in the perpendicular direction, and the
      difference between the two angles decreased with the increasing size of the water
      droplet.

PMID- 17559246
TI  - Stable aqueous nanoparticle film assemblies with covalent and charged polymer
      linking networks.
AB  - The construction of highly stable and efficiently assembled multilayer films of
      purely water soluble gold nanoparticles is reported. Citrate-stabilized
      nanoparticles (CS-NPs) of average core diameter of 10 nm are used as templates
      for stabilization-based exchange reactions with thioctic acid to form more robust
      aqueous NPs that can be assembled into multilayer films. The thioctic acid
      stabilized nanoparticles (TAS-NPs) are networked via covalent and electrostatic
      linking systems, employing dithiols and the cationic polymer poly(L-lysine),
      respectively. Multilayer films of up to 150 nm in thickness are successfully
      grown at biological pH with no observable degradation of the NPs within the film.
      The characteristic surface plasmon band, an optical feature of certain NP film
      assemblies that can be used to report the local environment and core spacing
      within the film, is preserved. Growth dynamics and film stability in solution and
      in the air are examined, with poly(L-lysine) linked films showing no evidence of
      aggregation for at least 50 days. We believe these films represent a pivotal step
      toward exploring the potential of aqueous NP film assemblies as a sensing
      apparatus.

PMID- 17559247
TI  - Gelled polymerizable microemulsions. 1. Phase behavior.
AB  - Microemulsions are gaining increasing importance as templates since a great deal
      is known about how to tune their structure and the size of the domains. The
      concept of synthesizing a bicontinuous high surface area polymer is well-known,
      by "arresting" the oil (water) phase and polymerizing the water (oil) phase.
      However, a general route for the 1:1 replication of the bicontinuous structure
      has not been found yet. Our approach to achieving this goal entails arresting the
      oil phase by gelling it, i.e., by forming an organogel, and polymerizing the
      aqueous phase. The ternary base system water-n-dodecane-Lutensol AO5 (technical
      grade nonionic n-alkyl polyglycol ether with an average molecular structure of
      C(13/15)E(5)) was chosen, and the organogelator 12-hydroxyoctadecanoic acid (12
      HOA) as well as a polymerizable aqueous phase containing the monomer N
      isopropylacrylamide (NIPAm) and the cross-linker N,N'-methylenebisacrylamide
      (BisAm) were added. To understand the influence of adding 12-HOA to the oil and
      NIPAM + BisAm to the aqueous phase on the phase behavior, phase diagrams were
      determined after each compositional change. The respective phase diagrams are
      presented and discussed in terms of their potential use as templates for new high
      surface area polymers.

PMID- 17559248
TI  - Experimental evidence of the motion of a single out-of-equilibrium drop.
AB  - We show experimentally that when a single, neutrally buoyant drop is injected
      into a binary mixture either it remains quiescent or it moves, depending on
      whether the composition of the drop and that of the surrounding phase coincide
      with the equilibrium concentrations. In general, the movement of out-of
      equilibrium drops, which is called diffusiophoresis, is induced by the Korteweg
      body force. This force is proportional to the chemical potential gradient and is
      therefore nonzero only when the system is in chemical nonequilibrium. In this
      letter, we show experimentally that this movement occurs for a single drop as
      well, even when the initial condition is (almost) isotropic. This instability,
      although it does not have a complete analytical explanation, has been predicted
      in the numerical simulations by Vladimirova et al. (Vladimirova, N.; Malagoli,
      A.; Mauri, R. Phys. Rev. E 1999, 60, 2037).

PMID- 17559249
TI  - An automated method for scanning LC-MS data sets for significant peptides and
      proteins, including quantitative profiling and interactive confirmation.
AB  - Differential quantification of proteins and peptides by LC-MS is a promising
      method to acquire knowledge about biological processes, and for finding drug
      targets and biomarkers. However, differential protein analysis using LC-MS has
      been held back by the lack of suitable software tools. Large amounts of
      experimental data are easily generated in protein and peptide profiling
      experiments, but data analysis is time-consuming and labor-intensive. Here, we
      present a fully automated method for scanning LC-MS/MS data for biologically
      significant peptides and proteins, including support for interactive confirmation
      and further profiling. By studying peptide mixtures of known composition, we
      demonstrate that peptides present in different amounts in different groups of
      samples can be automatically screened for using statistical tests. A linear
      response can be obtained over almost 3 orders of magnitude, facilitating further
      profiling of peptides and proteins of interest. Furthermore, we apply the method
      to study the changes of endogenous peptide levels in mouse brain striatum after
      administration of reserpine, a classical model drug for inducing Parkinson
      disease symptoms.

PMID- 17559250
TI  - Comparative proteomic expression profile in all-trans retinoic acid
      differentiated neuroblastoma cell line.
AB  - Neuroblastoma (NB) is an infant tumor which frequently differentiates into
      neurons. We used two-dimensional differential in-gel electrophoresis (2D-DIGE) to
      analyze the cytosolic and nuclear protein expression patterns of LAN-5 cells
      following neuronal differentiating agent all-trans-retinoic acid treatment. We
      identified several candidate proteins, from which G beta2 and Prefoldin 3 may
      have a role on NB development. These results strength the use of proteomics to
      discover new putative protein targets in cancer.

PMID- 17559251
TI  - A proteomics method revealing disease-related proteins in livers of hepatitis
      infected mouse model.
AB  - In this post-genome era, a sensitive quantitative method is required for
      differential profiling analyses of clinical proteomes to understand the disease
      progress. Here, we adopt the FD-LC-MS/MS method, consisting of fluorogenic
      derivatization (FD), separation by liquid chromatography (LC), and identification
      by LC-tandem mass spectrometry (MS/MS), to reveal disease-related proteins in
      livers of hepatocarcinogenesis in transgenic (Tg) and non-transgenic (NTg) mice
      at three developmental stages. After 6 months, the expression of apoptosis
      related proteins is suppressed. After 12 months, proteins related to respiration,
      the electron-transfer system, and anti-oxidation are significantly up-regulated.
      After 16 months, proteins related to defense, beta-oxidation, and apoptosis are
      significantly suppressed. This fluctuating expression of proteins could explain
      the progression of hepatocarcinogenesis. The method would be useful for clinical
      proteomics analysis because of its high resolution, sensitivity, and
      reproducibility.

PMID- 17559252
TI  - A platform for accurate mass and time analyses of mass spectrometry data.
AB  - We describe an integrated suite of algorithms and software for general accurate
      mass and time (AMT) tagging data analysis of mass spectrometry data. The AMT
      approach combines identifications from liquid chromatography (LC) tandem mass
      spectrometry (MS/MS) data with peptide accurate mass and retention time locations
      from high-resolution LC-MS data. Our workflow includes the traditional AMT
      approach, in which MS/MS identifications are located in external databases, as
      well as methods based on more recent hybrid instruments such as the LTQ-FT or
      Orbitrap, where MS/MS identifications are embedded with the MS data. We
      demonstrate our AMT workflow's utility for general data synthesis by combining
      data from two dissimilar biospecimens. Specifically, we demonstrate its use
      relevant to serum biomarker discovery by identifying which peptides sequenced by
      MS/MS analysis of tumor tissue may also be present in the plasma of tumor-bearing
      and control mice. The analysis workflow, referred to as msInspect/AMT, extends
      and combines existing open-source platforms for LC-MS/MS (CPAS) and LC-MS
      (msInspect) data analysis and is available in an unrestricted open-source
      distribution.

PMID- 17559253
TI  - Snake venomics of Bitis species reveals large intragenus venom toxin composition
      variation: application to taxonomy of congeneric taxa.
AB  - The protein composition of the venoms of the West African Gaboon viper (Bitis
      gabonica rhinoceros), the rhinoceros viper (Bitis nasicornis), and the horned
      puff adder (Bitis caudalis) were analyzed by RP-HPLC, N-terminal sequencing, SDS
      PAGE, MALDI-TOF peptide mass fingerprinting, and CID-MS/MS. In line with previous
      proteomic and transcriptomic analyses showing that snake venom proteins belong to
      only a few major protein families, the venom proteomes of Bitis gabonica
      rhinoceros, Bitis nasicornis, and Bitis caudalis comprise, respectively, toxins
      from 11, 9, and 8 toxin families. Dimeric disintegrins, PLA2 molecules, serine
      proteinases, a CRISP, C-type lectin-like proteins, L-amino acid oxidases, and
      snake venom metalloproteases are present in the three Bitis snake venoms, though
      they depart from each other in the composition and the relative abundance of
      their toxins. The venom composition appears to keep information on the
      evolutionary history of congeneric taxa. Protein similarity coefficients used to
      estimate the similarity of venom proteins of the Bitis taxa sampled here and in
      previous studies (eg. Bitis arietans and Bitis gabonica gabonica) support the
      monophyly of the three West African taxa (B.g. gabonica, B.g. rhinoceros, and B.
      nasicornis) based on genetic distance reconstructions, the lack of alliances
      between B. arietans and any other Bitis species, and are consistent with the
      taxonomic association of Bitis caudalis within the differentiated group of small
      Bitis species. The low level of venom toxin composition similarity between the
      two conventionally recognized subspecies of Bitis gabonica, B. g. gabonica and B.
      g. rhinoceros, supports the consideration by some authors of B. g. rhinoceros as
      a separate species, Bitis rhinoceros. Moreover, our proteomic data fit better to
      a weighted phylogram based on overall genetic distances than to an unweighted
      maximum-parsimony tree.

PMID- 17559254
TI  - Geometrical characteristics of polyelectrolyte nanogel particles and their
      polyelectrolyte complexes studied by dynamic and static light scattering.
AB  - The geometric characteristics of nanogel particles in aqueous solutions were
      studied by determining their ratios of radius of gyration (mean-square radius;
      Rg) to hydrodynamic radius (Rh), Rg/Rh, derived from static light scattering and
      dynamic light scattering experiments, respectively. The various nanogel samples
      studied included ones composed of lightly cross-linked N-isopropylacrylamide
      (NIPA) polymer, NIPA-based anionic or cationic copolymers, and amphoteric
      terpolymers. Polyelectrolyte complexes between anionic or cationic nanogels and
      oppositely charged polyions or nanogels having opposite charges were also
      studied. Most NIPA and NIPA-based polyelectrolyte nanogels in a swollen state had
      Rg/Rh values >0.775, which is the theoretically predicted value for a solid
      sphere. In a collapsed state, one may expect nanogel particles to be spherical in
      shape; however, this was not the case for a variety of nanogel samples, either
      with or without charges. These data were consistent with the idea that the
      surfaces of these nanogel particles were decorated with attached dangling chains.
      The Rg/Rh data from polyelectrolyte-nanogel complexes, however, indicated
      different structures from this. It was found that most of the polyelectrolyte
      nanogel complex particles had Rg/Rh approximately 0.775. This suggested that the
      complexed nanogel particles were spherical in shape and that there were no
      dangling surface chains.

PMID- 17559255
TI  - Photophysical properties of DASPMI as revealed by spectrally resolved
      fluorescence decays.
AB  - Photophysical properties of 2-(4-(dimethylamino)styryl)-1-methylpyridinium iodide
      (DASPMI) in various solvents were investigated using time- and space-correlated
      single photon counting. DASPMI is known to selectively stain mitochondria in
      living cells.1,2 The uptake and fluorescence intensity of DASPMI in mitochondria
      is a dynamic measure of membrane potential. Hence, an endeavor has been made to
      elucidate the mechanism of DASPMI fluorescence by obtaining spectrally resolved
      fluorescence decays in different solvents. A biexponential decay model was
      sufficient to globally describe the wavelength-dependent fluorescence in ethanol
      and chloroform. While in glycerol, a three-exponential decay model was necessary
      for global analysis. In the polar low-viscous solvent water, a monoexponential
      decay model fitted the decay data. The sensitivity of DASPMI to solvent viscosity
      was analyzed using various proportions of glycerol-ethanol mixtures. The
      lifetimes were found to increase with increasing solvent viscosity. The negative
      amplitudes of the short lifetime component found in chloroform and glycerol at
      the longer wavelengths validated the formation of new excited-state species from
      the initially excited state. Time-resolved emission spectra in chloroform and
      glycerol showed a biphasic increase of spectral width and emission maxima. The
      spectral width had an initial fast increase within 150 ps and a near constant
      thereafter. A three-state model of generalized scheme, on the basis of successive
      formation of locally excited state (LE), intramolecular charge transfer state
      (ICT), and twisted intramolecular charge transfer (TICT) state, has been proposed
      to explain the excited-state kinetics. The presumed role of solvation dynamics of
      ICT and TICT states leading to the asymmetrical broadening and structureless
      fluorescence has been substantiated by the decomposition of time-resolved
      emission spectra in chloroform, glycerol, and ethanol/glycerol mixtures.

PMID- 17559256
TI  - Equilibrium between quenched and nonquenched conformations of the major plant
      light-harvesting complex studied with high-pressure time-resolved fluorescence.
AB  - Nonphotochemical quenching (NPQ) of chlorophyll fluorescence plays an important
      role in the protection of plants against excessive light. Fluorescence quenching
      of the major light-harvesting complex (LHCII) provides a model system to study
      the mechanism of NPQ. The existence of both quenched and nonquenched states of
      LHCII has been postulated. We used time-resolved fluorescence and hydrostatic
      pressure to study differences between these states. Pressure shifts the
      thermodynamic equilibrium between the two states. The estimated volume difference
      was 5 mL/mol, indicating a local conformational switch. The estimated free energy
      difference was 7.0 kJ/mol: high enough to keep the quenched state population low
      under normal conditions, but low enough to switch in a controlled way. These
      properties are physiologically relevant properties, because they guarantee
      efficient light harvesting, while at the same time maintaining the capacity to
      switch to a quenched state. These results indicate that conformational changes of
      LHCII can play an important role in NPQ.

PMID- 17559257
TI  - Structural changes above the glass transition and crystallization in
      aluminophosphate glasses: an in situ high-temperature MAS NMR study.
AB  - We present an in situ high-temperature nuclear magnetic resonance study on the
      structural changes in aluminophosphate glasses occurring in the temperature range
      between the glass transition temperature Tg and the crystallization temperature
      Tc, Tg < T < Tc. Decisive changes in the network organization between Tg and Tc
      in potassium aluminophosphate glasses in the compositional range 50K2O-xAl2O3-(50
      - x)P2O5 with 2.5 < x < 20 could be monitored for the first time employing 1D 31P
      and 27Al-MAS NMR. Accompanying ex situ NMR experiments (31P-RFDR NMR and 31P
      {27Al} CP-HETCOR NMR) on devitrified samples were performed at room temperature
      to further characterize the phases formed during the crystallization process. The
      structural role of boron-which is known to inhibit the crystallization process in
      these aluminophosphate glasses-on short and intermediate length scales was
      analyzed employing 11B-MQMAS, 11B-{27Al} TRAPDOR and 11B-{31P} REDOR NMR
      spectroscopy.

PMID- 17559258
TI  - Electrical, optical, thermoelectric power, and dielectrical properties of organic
      semiconductor poly(1,12-bis(carbazolyl) dodecane) film.
AB  - Electrical conductivity, optical, thermoelectric, and dielectrical properties of
      the poly(1,12-bis(carbazolyl) dodecane) film have been investigated. The
      activation energy for electrical conductivity and room-temperature electrical
      conductivity (at 25 degrees C) values were found to be 0.25 eV and 2.65 x 10-6
      S/cm, respectively. The thermoelectric power results suggest that the
      conductivity is due to large polarons (i.e., the carriers in polymer move by
      hopping in the localized states at band gap edges). Electrical conductivity and
      thermoelectric power results confirm that the polymer is a p-type organic
      semiconductor. Optical absorption results suggest that the direct allowed
      transitions are dominant in the fundamental absorption edge in the polymer with
      optical band gap value of 2.72 eV. The refractive index dispersion of the polymer
      obeys the single oscillator model with oscillator energy (Eo = 3.06 eV) and
      dispersion energy (Ed = 17.82 eV) values. Alternating current conductivity
      results suggest that the hopping conductivity is dominant in the polymer. The
      dielectrical properties exhibit a non-Debye relaxation.

PMID- 17559259
TI  - Solvation and aggregation of polyphenylethynylene based anionic polyelectrolytes
      in dilute solutions.
AB  - The absorption and fluorescence properties of a polyphenylethynylene based
      conjugated polyelectrolyte with sulfonate solubilizing groups (PP2) are shown to
      change dramatically with solution conditions because of the equilibrium between
      unaggregated and aggregated forms of the polymer. The fluorescence of PP2 is
      strongly quenched on addition of counterions such as Na+, K+, Li+, and TBA+, an
      effect which arises from the creation of salt stabilized aggregates. The
      formation of aggregates has been further corroborated by concentration and
      temperature studies in water and comparisons to dimethylsulfoxide solvent, in
      which the polymer does not aggregate. In aqueous solutions, the addition of the
      cationic surfactant, octadecyltrimethyl ammonium, causes the polymer aggregates
      to dissociate and creates polymer/surfactant aggregates that have spectral
      properties like that of the unaggregated polymer.

PMID- 17559260
TI  - Using intrinsic X-ray absorption spectral differences to identify and map
      peptides and proteins.
AB  - The intrinsic variation in the near-edge X-ray absorption fine structure (NEXAFS)
      spectra of peptides and proteins provide an opportunity to identify and map them
      in various biological environments, without additional labeling. In principle,
      with sufficiently accurate spectra, peptides (<50 amino acids) or proteins with
      unusual sequences (e.g., cysteine- or methionine-rich) should be differentiable
      from other proteins, since the NEXAFS spectrum of each amino acid is distinct. To
      evaluate the potential for this approach, we have developed X-SpecSim, a tool for
      quantitatively predicting the C, N, and O 1s NEXAFS spectra of peptides and
      proteins from their sequences. Here we present the methodology for predicting
      such spectra, along with tests of its precision using comparisons to the spectra
      of various proteins and peptides. The C 1s, N 1s, and O 1s spectra of two novel
      antimicrobial peptides, Indolicidin (ILPWKWPWWPWRR-NH2) and Sub6 (RWWKIWVIRWWR
      NH2), as well as human serum albumin and fibrinogen are reported and interpreted.
      The ability to identify, differentiate, and quantitatively map an antimicrobial
      peptide against a background of protein is demonstrated by a scanning
      transmission X-ray microscopy study of a mixture of albumin and sub6.

PMID- 17559261
TI  - Theoretical study of N-demethylation of substituted N,N-dimethylanilines by
      cytochrome P450: the mechanistic significance of kinetic isotope effect profiles.
AB  - The mechanism of N-demethylation of N,N-dimethylanilines (DMAs) by cytochrome
      P450, a highly debated topic in mechanistic bioinorganic chemistry (Karki, S. B.;
      Dinnocenczo, J. P.; Jones, J. P.; Korzekwa, K. R. J. Am. Chem. Soc. 1995, 117,
      3657), is studied here using DFT calculations of the reactions of the active
      species of the enzyme, Compound I (Cpd I), with four para-(H, Cl, CN, NO2)
      substituted DMAs. The calculations resolve mechanistic controversies, offer a
      consistent mechanistic view, and reveal the following features: (a) the reaction
      pathways involve C-H hydroxylation by Cpd I followed by a nonenzymatic
      carbinolamine decomposition. (b) C-H hydroxylation is initiated by a hydrogen
      atom transfer (HAT) step that possesses a "polar" character. As such, the HAT
      energy barriers correlate with the energy level of the HOMO of the DMAs. (c) The
      series exhibits a switch from spin-selective reactivity for DMA and p-Cl-DMA to
      two-state reactivity, with low- and high-spin states, for p-CN-DMA and p-NO2-DMA.
      (d) The computed kinetic isotope effect profiles (KIEPs) for these scenarios
      match the experimentally determined KIEPs. Theory further shows that the KIEs and
      TS structures vary in a manner predicted by the Melander-Westheimer postulate: as
      the substituent becomes more electron withdrawing, the TS is shifted to a later
      position along the H-transfer coordinate and the corresponding KIEs increases.
      (e) The generated carbinolaniline can readily dissociate from the heme and
      decomposes in a nonenzymatic environment, which involves water assisted proton
      shift.

PMID- 17559262
TI  - Correlation between the dynamics of hydrogen bonds and the local density
      reorganization in the protein hydration layer.
AB  - An atomistic molecular dynamics simulation of the protein villin headpiece
      subdomain or HP-36 has been carried out with explicit water to explore the
      microscopic inhomogeneity of local density reorganization of the hydration layers
      of the three alpha-helical segments of the protein. The density reorganization of
      the hydration layer of helix-3 is found to occur faster than that for the
      hydration layers of the other two helices. It is noticed that such inhomogeneous
      density reorganization at the surface of different secondary structures exhibits
      excellent correlation with the microscopic dynamics of hydrogen bonds between the
      protein residues and the hydration water. Further, it is observed that the
      reorientation of water molecules involved in the formation and breaking of
      protein-water or water-water hydrogen bonds plays an important role in
      determining the dynamics of local density of the hydration layer. The faster
      density reorganization of the hydration layer of helix-3 is also consistent with
      the functionality of HP-36, as helix-3 contains several active site residues.

PMID- 17559263
TI  - Biodegradable nanogel formation of polylactide-grafted dextran copolymer in
      dilute aqueous solution and enhancement of its stability by stereocomplexation.
AB  - Monodisperse stereocomplex nanogels were obtained through the self-assembly of an
      equimolar mixture of dextran-graft-poly(L-lactide) (Dex-g-PLLA) and dextran-graft
      poly(D-lactide) (Dex-g-PDLA) amphiphilic copolymers with well-defined composition
      in a dilute aqueous solution. The stereocomplex nanogel possessed partially
      crystallized cores of hydrophobic polylactide (PLA) and the hydrophilic dextran
      skeleton by intra- and/or intermolecular self-assembly between PLLA and PDLA
      chains. The stereocomplex nanogels exhibited significantly lower critical
      aggregation concentration (CAC) value as well as stronger thermodynamic stability
      compared with those of the corresponding L- or D-isomer nanogels. The mean
      diameter of the stereocomplex nanogels was 70 nm with narrow size distribution,
      implying they were well-defined and presumably nanogels. Furthermore,
      stereocomplex nanogel exhibited strong kinetic stability. The tunable degradation
      properties of Dex-g-PLA nanogels were achieved by varying the number of grafted
      PLA chains as well as applying stereocomplexation. This study demonstrates the
      advantage of stereocomplexation in the design of biodegradable nanogels with
      enhanced stability.

PMID- 17559264
TI  - Characterization of the myricetin-human serum albumin complex by spectroscopic
      and molecular modeling approaches.
AB  - The interaction mechanism of flavonol myricetin (3,5,7,3',4',5'
      hexahydroxyflavone) and human serum albumin (HSA) has been characterized by
      fluorescence, electronic absorption, and Fourier transform infrared (FT-IR)
      spectroscopic approaches and the molecular modeling method. The structural
      characteristics of myricetin and HSA were probed, and their binding affinities
      were determined under different pH conditions. The results showed that the
      binding abilities of the drug to protein decreased under lower pH conditions (pH
      3.5 and 2.0) due to the alterations of the protein secondary and tertiary
      structures. The second derivative absorption spectra of myricetin after
      interacting with the protein showed that the drug existed as an anion form in the
      binding pocket. The fluorescence emission intensities of the normal and excited
      state proton transfer (ESTP) tautomer of myricetin significantly enhanced in the
      presence of HSA with conspicuous shifts of the emission bands when excited with a
      wavelength of 370 nm, while the intensity ratios of the normal to ESTP tautomers
      rose rapidly with the increase of the HSA concentrations under different pH
      environments. This illustrated that the fluorescence emission of the normal
      tautomer (S1-S0, non-proton-transferred) predominated due to the interaction of
      drug and surrounding polar and ionic side chains of amino acid residues in the
      binding cavity. The similar spectroscopic properties of myricetin-HSA complex at
      pH 7.4 and 3.5 showed that the drug was located in subdomain IIA of the protein
      in the vicinity of the single Trp 214 because of the unfolding of the protein
      domain III in its F state. From the molecular modeling results, the drug-protein
      complex was stabilized by electrostatic force and hydrogen bonding with the amino
      acid residue in the binding pocket, which was consistent with the experimental
      results.

PMID- 17559265
TI  - Anti-inflammatory benzenoids from Antrodia camphorata.
AB  - Four new compounds, including three new benzenoids, antrocamphin A (1),
      antrocamphin B (2), and 2,3,4,5-tetramethoxybenzoyl chloride (3), and a new 1,3
      dioxolan-2-one derivative, antrodioxolanone (4), together with 13 known compounds
      have been isolated from the fruiting body of Antrodia camphorata. The structures
      of these new compounds were determined through spectral analyses including
      extensive 2D-NMR data. Among the isolates, antrocamphin A (1), antcin A (10), and
      antcin B (11) exhibited potent inhibition against fMLP-induced superoxide
      production with IC50 values less than 10 microM.

PMID- 17559266
TI  - Biotransformation of polymethoxylated flavonoids: access to their 4'-O
      demethylated metabolites.
AB  - Regioselective O-demethylation of the flavones tangeretin (1) and 3
      hydroxytangeretin (6) into their 4'-O-demethylated metabolites was performed by
      using an Aspergillus niger strain. This method serves as a straightforward
      alternative to multistep synthesis or semisynthesis. The microbial approach is
      complementary to the chemical procedure, which furnishes a 5-O-demethylated
      product. P450 inhibitors prevented the biotransformation of tangeretin (1). These
      results suggest that a P450 oxidation system might be involved in this O
      demethylation and demonstrate a consequent similarity in both microbial and
      mammalian metabolism of polymethoxylated flavones.

PMID- 17559267
TI  - Probing the bioactive constituents from chemotypes of the sponge Psammocinia aff.
      bulbosa.
AB  - Since the report of (+)-psymberin (2) in 2004, many synthetic groups have pursued
      the synthesis of this compound, and our group has further collected Psammocinia
      aff. bulbosa to successfully isolate more 2. With more (+)-psymberin (2) in hand,
      additional clonogenic studies, a therapeutic efficacy assessment, and the hollow
      fiber assay have been completed. The inconsistent production of (+)-psymberin (2)
      and the classification of six Psammocinia species are further discussed herein.
      The most recent of these six collections resulted in the isolation of a new
      brominated cyclic peptide, (-)-psymbamide A (4), which is the first report of a
      Psammocinia-derived compound in this peptide class. The planar structure was
      solved via dereplication with Marinlit, HRESIMS, and 1D and 2D NMR techniques,
      and the absolute configuration determined using Marfey's method.

PMID- 17559270
TI  - Nickel-NHC-catalyzed alpha-arylation of acyclic ketones and amination of
      haloarenes and unexpected preferential N-arylation of 4-aminopropiophenone.
AB  - Arylation of both acyclic ketones and primary and secondary amines was achieved
      using a new, simple, stable, and easy-to-access nickel(II)-halide complex bearing
      mixed PPh3/N-heterocyclic carbene ligands as a catalyst precursor. Acyclic
      ketones were first arylated at the alpha-position with the nickel catalyst. On
      the other hand, less basic amines, such as diphenylamine and 4-aminobenzophenone,
      were more favorable in the catalytic amination of haloarenes than basic amines,
      contrary to previous reports. N-Arylation of 4-aminopropiophenone was found to
      proceed selectively without causing alpha-arylation of the ketone group.

PMID- 17559271
TI  - A kinetic study of the conjugate addition of benzenethiol to cyclic enones
      catalyzed by a nonsymmetrical uranyl-salophen complex.
AB  - The Et3N-assisted addition of benzenethiol to enones in chloroform is catalyzed
      with high turnover efficiency by the phenyl-substituted uranyl-salophen compound
      3. Catalytic data show a close adherence to a quatermolecular mechanism involving
      reaction of a base-activated thiol with a reversibly formed complex of enone and
      metal catalyst, with a complication of product inhibition due to the formation of
      a product-catalyst complex. The role of the binding energy made available by
      interactions with the aromatic sidearm of the catalyst is discussed in terms of
      catalyst-substrate and catalyst-transition state complementarity.

PMID- 17559269
TI  - Palladium-catalyzed synthesis of nucleoside adducts from bay- and fjord-region
      diol epoxides.
AB  - Palladium-catalyzed C-N bond formation has been utilized to synthesize covalent
      2'-deoxyadenosine (dA) and 2'-deoxyguanosine (dG) adducts of benzo[a]pyrene (BaP)
      series 1 (syn) and benzo[c]phenanthrene (BcPh) series 2 (anti) diol epoxides. For
      this, (+/-)-10 alpha-amino-7 beta,8 alpha,9 beta-trisbenzoyloxy-7,8,9,10
      tetrahydro BaP and (+/-)-1 beta-amino-2 alpha,3 alpha,4 beta-trisbenzoyloxy
      1,2,3,4-tetrahydro BcPh were coupled with 6-halo-9-[3,5-bis-O-(tert
      butyldimethylsilyl)-beta-D-erythro-pentofuranosyl]purine and O6-benzyl-3',5'-bis
      O-(tert-butyldimethylsilyl)-2-bromo-2'-deoxyinosine, using a (+/-)-BINAP-Pd
      complex and Cs2CO3. For the synthesis of the dA adducts, both the 6-chloro- as
      well as the 6-bromopurine nucleoside derivatives were analyzed for the C-N
      coupling reaction with the hydrocarbon amino tribenzoates. With the BaP amino
      tribenzoate, the 6-chloronucleoside provided satisfactory results, whereas the 6
      bromo analogue proved to be superior with the BcPh amino tribenzoate. Overall,
      lower yields of the dA adducts were obtained with the more hindered fjord-region
      BcPh amino tribenzoate as compared to the bay-region BaP amino tribenzoate. In
      contrast to reactions leading to the dA adducts, the C-N reactions of both BaP
      and BcPh amino tribenzoates with the 2-bromo-2'-deoxyinosine derivative proceeded
      in comparable yields. This seems to indicate that such Pd-catalyzed adduct
      forming reactions at the C-6 position may be influenced by steric constraints of
      the amine component, whereas those at the C-2 position are less sensitive.
      Diastereomeric adduct pairs were separated and characterized by spectral methods
      and by comparisons to adducts produced by direct displacement reactions as well
      as those formed from DNA alkylation by diol epoxides.

PMID- 17559272
TI  - Solid-phase synthesis of chlorofusin analogues.
AB  - We report an efficient and versatile solid-phase synthesis through which two
      series of chlorofusin analogues, one bearing varying chromophores and the other
      with various amino acid substitutions in the cyclic peptide, were synthesized.
      These peptides were prepared using a strategy involving side-chain
      immobilization, on-resin cyclization, and postcyclization modification. The
      success of these syntheses demonstrates the broad utility of the method. Both
      series of analogues were evaluated for their inhibitory activity against the
      p53/MDM2 interaction but were shown to be inactive in the concentration range
      tested. This suggests that the full chromophore structure may be required for
      activity.

PMID- 17559273
TI  - A general modular method of azaindole and thienopyrrole synthesis via Pd
      catalyzed tandem couplings of gem-dichloroolefins.
AB  - A palladium-catalyzed reaction of gem-dichloroolefins and a boronic acid via a
      tandem intramolecular C-N and intermolecular Suzuki coupling process gave
      corresponding substituted azaindoles or thienopyrroles. This method is a very
      modular protocol to synthesize all four isomers of azaindole and two isomers of
      thienopyrroles in good to excellent yield.

PMID- 17559274
TI  - Conversion of Ni(II)-allylporphyrins to alpha,beta-unsaturated formylporphyrins
      via a nickel-promoted reaction.
AB  - A new route to alpha,beta-unsaturated formylporphyrins begins with the synthesis
      of allyl-substituted porphyrins via the Suzuki cross-coupling reaction of
      bromoporphyrins and allylboronic acid pinacol ester in 50-95% yield. Treatment of
      allyl-substituted porphyrins with nickel acetate in N,N-dimethylformamide (DMF)
      then affords mono- and diacroleinylporphyrins in up to 70% yield.

PMID- 17559275
TI  - Enantioselective allylation of ketones catalyzed by N,N'-dioxide and indium(III)
      complex.
AB  - Complexes of (S)-pipecolic acid-, L-proline-, and other amino acid-derived N,N'
      dioxides coordinated with different metal ions have been investigated in the
      enantioselective allylation of ketones. A variety of aromatic ketones were found
      to be suitable substrates in the presence of the L1-In(III) complex, and afforded
      the corresponding homoallylic alcohols with good enantioselectivites (up to 83%
      ee) and moderate to high yields (up to 94%). On the basis of the experimental
      results, a possible catalytic cycle including a transition state has been
      proposed to explain the origin of the reactivity and asymmetric inductivity, and
      a bifunctional catalyst was described with Lewis base N-oxide activating
      tetraallyltin and Lewis acid indium activating ketone.

PMID- 17559276
TI  - Phosphatidylinositol mannoside ether analogues: syntheses and interleukin-12
      inducing properties.
AB  - Phosphatidylinositol mannosides (PIMs) isolated from mycobacteria have been
      identified as an important class of glycolipids with significant immune
      modulating properties. We present here the syntheses of phosphatidylinositol
      dimannoside ether analogues 2 and 3 and evaluate their interleukin-12 (IL-12)
      inducing properties along with dipalmitoyl PIM2 (1) in an in vitro bovine
      dendritic cell assay. Both synthetic PIM analogues and synthetic dipalmitoyl PIM2
      (1) were effective at enhancing IL-12 production by immature bovine dendritic
      cells. Unexpectedly, ether analogue 2 was significantly more active than
      dipalmitoyl PIM2 (1) which indicates that modified PIM compounds can be strongly
      immunoactive and may have significant adjuvant activities.

PMID- 17559278
TI  - Wittig reactions in water media employing stabilized ylides with aldehydes.
      Synthesis of alpha,beta-unsaturated esters from mixing aldehydes, alpha
      bromoesters, and Ph3P in aqueous NaHCO3.
AB  - Water is demonstrated to be an effective medium for the Wittig reaction over a
      wide range of stabilized ylides and aldehydes. Despite sometimes poor solubility
      of the reactants, good chemical yields normally ranging from 80 to 98% and high E
      selectivities (up to 99%) are achieved, and the rate of the reactions in water is
      unexpectedly accelerated. The efficiency of water as a medium in the Wittig
      reaction is compared to conventional organic solvents ranging from carbon
      tetrachloride to methanol. The aqueous Wittig reaction works best when large
      hydrophobic entities are present, such as aromatic, heterocyclic aromatic
      carboxaldehydes, and long-chain aliphatic aldehydes with triphenylphosphoranes.
      The E/Z-isomeric ratio of the Wittig products appears dependent on the electron
      accepting/donating capacity and the location of the substituents present in the
      aromatic ring. The effect of additives, such as benzoic acid, LiCl, and sodium
      dodecyl sulfate (SDS), on the Wittig reaction has been explored. The Wittig
      reaction can also be conducted in the presence of acidic entities, such as
      phenols and carboxylic acids. In addition, large alpha-substituents in the
      aliphatic aldehydes do not jeopardize the reaction. It is also demonstrated that
      hydrates of aldehydes can be used directly in the aqueous Wittig reaction as
      substrates. The scope of the aqueous Wittig reaction is extended to 24 examples
      of one-pot mixtures of Ph3P, alpha-bromoesters, and aldehydes in sodium
      bicarbonate solution (at 20 degrees C for 40 min to 3 h) to provide Wittig
      products of up to 99% yield and up to 98% E-selectivity. Since water is
      inexpensive, extremely easy to handle, and represents no environmental concerns,
      it should be considered a possible medium for new organic reactions.

PMID- 17559277
TI  - Regioselective synthesis of 4- and 7-alkoxyindoles from 2,3-dihalophenols:
      application to the preparation of indole inhibitors of phospholipase A2.
AB  - An efficient and regioselective synthesis of 4- and 7-alkoxyindoles has been
      developed from commercially available starting materials such as 3-halophenols
      and 3-chloroanisole. Directed ortho-metalation followed by two palladium
      catalyzed processes, a Sonogashira coupling and a tandem amination/cyclization
      reaction, allows the synthesis of regiochemically pure 4- and 7-substituted
      indoles. This strategy has been successfully applied to the preparation of 2-[3
      (2-amino-2-oxoacetyl)-1-benzyl-2-ethyl-1H-indol-4-yloxy]acetic acid (LY315920), a
      known inhibitor of phospholipase A2.

PMID- 17559279
TI  - Synthesis of biladienone and bilatrienone by coupled oxidation of
      tetraarylporphyrins.
AB  - Tetraarylbiladien-ab-ones bearing various substituents (R) in the para position
      of the phenyl groups were preprared by coupled oxidation of tetraarylporphyrin
      iron complexes. The yields of 5,10,15-triaryl-19-aroyl-15-hydroxybiladien-ab-ones
      were 74% (R=H), 85% (R=OMe), 44% (R=COOMe), and 28% (R=CN). Kinetic studies of
      the iron porphyrin oxidation revealed that the reaction is accelerated by an
      electron-withdrawing substituent with the Hammett reaction constant rho=0.295.
      5,10,15-Triaryl-19-aroyl-15-hydroxybiladien-ab-ones undergo the acid-catalyzed
      elimination reaction either by acetic acid or by mesoporous silica to afford
      5,10,15-triaryl-19-aroylbilatrien-abc-one. The elimination reaction in acetic
      acid is accelerated by an electron-donating substituent with the Hammett reaction
      constant rho=-1.48.

PMID- 17559280
TI  - Trans-(+/-)-2-tert-butyl-3-phenyloxaziridine: a unique reagent for the oxidation
      of thiolates into sulfenates.
AB  - Aliphatic thiolates were efficiently converted into the corresponding sulfenates
      by smooth oxidation with trans-(+/-)-2-tert-butyl-3-phenyloxaziridine at room
      temperature (five examples). Subsequent electrophilic quench with benzyl bromide
      led to sulfoxides (S-alkylation) in good to moderate yields. Application of the
      protocol to an aromatic substrate was also successful. This work represents the
      first valuable example of the use of this poorly active oxidizing agent in
      synthetic organic chemistry without the need for activating conditions.

PMID- 17559281
TI  - Selective synthesis of 2,3-disubstituted-2H-isoindol-1-ylphosphonate and 2,3
      disubstituted-1,2-dihydroiso-quinolin-1-ylphosphonate via metal-tuned reaction of
      alpha-amino (2-alkynylphenyl)methylphosphonate.
AB  - Palladium(II)-catalyzed reaction of alpha-amino (2
      alkynylphenyl)methylphosphonate provides a novel and efficient route to 2,3
      disubstituted-2H-isoindol-1-ylphosphonate via 5-exo-cyclization and [1,5]-H
      shift; while 2,3-disubstituted-1,2-dihydroisoquinolin-1-ylphosphonate is afforded
      through 6-endo-cyclization utilizing silver triflate as catalyst.

PMID- 17559282
TI  - Metal-free access to fully substituted skipped diynes. An efficient
      chemodifferentiating A2BB' 4CR manifold.
AB  - A metal-free chemodifferentiating A2BB' 4CR manifold for the modular synthesis of
      tertiary skipped diynes is described. The manifold performs a triethylamine
      triggered reaction of alkyl propiolates and acid chlorides to assemble two units
      of each component in the form of two propargylic alkynoates, a tertiary alcohol,
      and an ester. A differentiated incorporation of the two acid chloride components
      ensures functional diversity in the final structure. In addition, the presence of
      two connected propargylic alkynoates provides a reactive platform for complexity
      generation.

PMID- 17559283
TI  - Enols of substituted cyanomalonamides.
AB  - Twenty open-chain mono-, di-, and trialkyl and aryl-N-substituted
      cyanomalonamides R2R1NCOCH(CN)CONHR3 were prepared. In solution, signals for both
      amide and a single enol are mostly observed, despite the potential for E and Z
      isomeric enols. The equilibrium (KEnol) values between the amides and the enols
      were determined in different solvents by NMR spectra. They decrease on increasing
      the polarity of the solvent in the order CDCl3 approximately C6D6>THF
      d8>(CD3)2CO>CD3CN>DMF-d7>DMSO-d6. For the R1R2NCOCH(CN)CONHR3 system when
      R1=R2=H, Me or R1=H, R2=Me, KEnol for R3 follows the order: C6F5>Ph>or=An>or= i
      Pr>or= t-Bu, and for R1, R2:H, H>Me, H>Me, Me in all solvents. A unique feature
      is the appreciable % enol in DMSO-d6 when R1=R2=H, in contrast with enol systems
      with other electron-withdrawing groups (EWGs). Calculations (B3LYP/6-31G**)
      corroborate the higher KEnol values for less alkyl-substituted systems, showing
      that in the most stable conformer when R1=H, R2=R3=Me the N-hydrogens are closer
      to the CN group. The order of promoting substituents for enol of amide formation
      is CONH2>CO2CH2CF3>CO2Me>CONHMe. The solid-state structures of the isolated
      species, determined by X-ray crystallography, were either amides or enols, and a
      higher KEnol(CDCl3) value does not ensure a solid enol structure. In no system
      were both solid species isolated. The X-ray structures of the enols were
      temperature-dependent. In most cases, the difference between the O-H and O...H
      bond lengths at low temperature were appreciable, but they become closer at the
      higher temperature. Similar tendency for either the C=C/C-C or the C-O/C=O bonds
      was observed. This is ascribed to a hydrogen shift between two regioisomeric
      enols in an asymmetric double-well potential, which becomes faster at a higher
      temperature. Calculations show that the enol structures are nonsymmetrical,
      resembling the lower temperature structures, even when they are chemically
      symmetrical, but the energy differences between the two regioisomers are <1 kcal.
      The hydrogen bonds in the enol moiety are strong, with O...O distances <2.45 A,
      and are resonance-assisted hydrogen bonds. IR spectra in solution and the solid
      state qualitatively corroborate the NMR and X-ray structure determination.

PMID- 17559284
TI  - Carbon nanotube/detergent interactions via coarse-grained molecular dynamics.
AB  - Detergent interactions with carbon nanotubes are of potential importance in a
      number of bionanotechnology applications. We investigate the interaction of
      lysophospholipids with single-walled carbon nanotubes via coarse-grained
      molecular dynamics. We present compelling evidence that the mechanism of
      adsorption of these detergents onto a carbon nanotube is dependent upon detergent
      concentration. Furthermore, the chirality of the carbon nanotube influences the
      detergent wrapping angle for low detergent concentration. These findings advance
      our understanding of the mechanism of carbon nanotube solubilization via
      detergent molecules.

PMID- 17559285
TI  - Unfolding of ribonuclease A on silica nanoparticle surfaces.
AB  - This paper reports on the unfolding behavior of ribonuclease A (RNase A) on
      silica nanoparticle surfaces and quantitively demonstrates that nanoscale size
      and surface curvature play key roles in influencing the stability of adsorbed
      proteins. Urea denaturation analyses showed that the thermodynamic stability of
      RNase A decreased upon adsorption onto the nanoparticles, with greater decrease
      on larger nanoparticles. The stability changes of RNase A correlate well with the
      changes in the protein-nanoparticle interactions, which increase as the surface
      contact area and surface charge interaction increases. This study, therefore,
      provides fundamental information on the effect of nanoscale surfaces on protein
      structure and function.

PMID- 17559287
TI  - Simultaneous electrical transport and scanning tunneling spectroscopy of carbon
      nanotubes.
AB  - We performed scanning tunneling spectroscopy measurements on suspended single
      walled carbon nanotubes with independently addressable source and drain
      electrodes in the Coulomb blockade regime. This three-terminal configuration
      allows the resistance to the source and drain electrodes to be individually
      measured, which we exploit to demonstrate that electrons were added to spin
      degenerate states of the carbon nanotube. Unexpectedly, the Coulomb peaks also
      showed a strong spatial dependence. By performing simultaneous scanning tunneling
      spectroscopy and electrical transport measurements we show that the probed states
      are extended between the source and drain electrodes. This indicates that the
      observed spatial dependence reflects a modulation of the contact resistance.

PMID- 17559288
TI  - Imaging of the Schottky barriers and charge depletion in carbon nanotube
      transistors.
AB  - The photovoltage produced by local illumination at the Schottky contacts of
      carbon nanotube field-effect transistors varies substantially with gate voltage.
      This is particularly pronounced in ambipolar nanotube transistors where the
      photovoltage switches sign as the device changes from p-type to n-type. The
      detailed transition through the insulating state can be recorded by mapping the
      open-circuit photovoltage as a function of excitation position. These
      photovoltage images show that the band-bending length can grow to many microns
      when the device is depleted. In our palladium-contacted devices, the Schottky
      barrier for electrons is much higher than that for holes, explaining the higher p
      type current in the transistor. The depletion width is 1.5 mum near the n-type
      threshold and smaller than our resolution of 400 nm near the p-type threshold.
      Internal photoemission from the metal contact to the carbon nanotube and
      thermally assisted tunneling through the Schottky barrier are observed in
      addition to the photocurrent that is generated inside the carbon nanotube.

PMID- 17559291
TI  - Hyperresponsive sensory patterns in young children with autism, developmental
      delay, and typical development.
AB  - The nature of hyperresponsiveness to sensory stimuli in children with autism,
      using a new observational measure, the SPA, was examined. Three groups of young
      participants were assessed (autism, developmental delay, typical). Across all
      groups, MA was a predictor of hyperresponsiveness, such that aversion to
      multisensory toys decreased as MA increased. The two clinical groups displayed
      higher levels of sensory aversion than the typical group. The groups did not
      differ in the proportion of children habituating to an auditory stimulus;
      however, nonresponders were more prevalent in the autism group. These findings
      elucidate developmental influences on sensory features and the specificity of
      hyperresponsiveness to clinical groups. Implications for understanding
      pathogenesis, differentiating constructs of hypersensitivity, and planning
      treatment are discussed.

PMID- 17559292
TI  - Discovering indices of contingency awareness in adults with multiple profound
      disabilities.
AB  - We conducted two studies to examine parameters of social attention in contingency
      awareness training using switch activation with individuals who had multiple
      profound disabilities. In Study 1 we compared leisure devices and social
      attention as reinforcing stimuli with 5 individuals. Results indicated the
      reinforcing qualities of social attention over leisure devices with 2 individuals
      and documented the importance of session length in training. In Study 2 we
      investigated idiosyncratic behaviors as indicators of responsiveness with 3 of
      the 5 original participants as they activated switches. Behavior changes during
      switch activation versus nonactivation times in the leisure device and social
      attention conditions suggested volitional movement supporting contingency
      awareness and preference. Implications for clinical practice are discussed.

PMID- 17559293
TI  - Divorce in families of children with Down syndrome: a population-based study.
AB  - In this study, we examined the nature, timing, and correlates of divorce in
      families of children with Down syndrome (647), other birth defects (10,283) and
      no identified disability (361,154). Divorce rates among families of children with
      Down syndrome were lower than in the other two groups. When divorce did occur in
      the Down syndrome group, however, a higher proportion occurred within the first 2
      years after the child's birth. Mothers and fathers of children with Down syndrome
      were much more likely to divorce if they were younger, had not graduated from
      high school, and if fathers were less educated and lived in a rural area. Few
      effects on divorce were noted for a variety of family structure variables.

PMID- 17559294
TI  - Measuring parental daily rewards and worries in the transition to adulthood.
AB  - Psychometric properties are described for an inventory that measures the daily
      rewards and worries that parents experience as their sons and daughters
      transition to adulthood. In a series of 4 studies involving 847 respondents, we
      explored and confirmed the factor structure of the Transition Daily Rewards and
      Worries Questionnaire (TDRWQ) in a sample that included transitioning individuals
      with and without disabilities. The final questionnaire includes 28 items in 4
      factors: Positive Future Orientation, Community Resources, Financial
      Independence, and Family Relations. Evidence of acceptable internal and test-
      retest reliability is presented, as is discriminant and convergent validity. The
      TDRWQ should enhance the quantitative approach to understanding parental
      reactions as sons and daughters make the transition to adulthood.

PMID- 17559295
TI  - Narrative development in adolescents and young adults with fragile x syndrome.
AB  - The narratives of 18 adolescents and young adults with fragile X syndrome were
      compared to those of 23 adolescents with Down syndrome and 21 typically
      developing children matched for nonverbal MA. Narratives were elicited using a
      wordless picture book and analyzed for use of narrative evaluation, linguistic
      productivity, and complexity. Results revealed that the individuals with fragile
      X syndrome produced significantly fewer different types of narrative evaluation,
      but more grammatically acceptable utterances than did the youth with Down
      syndrome. There was no significant difference between the participants with
      fragile X syndrome and their typically developing nonverbal-MA matches. Results
      suggest that a variety of language measures and contexts are needed to gain a
      full understanding of the language abilities of individuals with fragile X
      syndrome.

PMID- 17559296
TI  - Tremor frequency profile as a function of level of mental retardation.
AB  - The characteristic slowness of movement initiation and execution in adult
      individuals with mental retardation may be driven by the slower frequency profile
      of the dynamics of the system. To investigate this hypothesis, we examined the
      resting and postural finger tremor frequency profile (single and dual limb) of
      adults as a function of level of mental retardation (moderate, severe, profound).
      There was a progressive increase in the contribution of slow frequency components
      to the enhanced amplitude of tremor as a function of mental retardation,
      particularly in the group with profound mental retardation. Findings support the
      hypothesis of mental retardation inducing a slower frequency to the system
      dynamics that may fundamentally drive the characteristic slowness of movement
      behavior.

PMID- 17559298
TI  - A survey of genomic properties for the detection of regulatory polymorphisms.
AB  - Advances in the computational identification of functional noncoding
      polymorphisms will aid in cataloging novel determinants of health and identifying
      genetic variants that explain human evolution. To date, however, the development
      and evaluation of such techniques has been limited by the availability of known
      regulatory polymorphisms. We have attempted to address this by assembling, from
      the literature, a computationally tractable set of regulatory polymorphisms
      within the ORegAnno database (http://www.oreganno.org). We have further used 104
      regulatory single-nucleotide polymorphisms from this set and 951 polymorphisms of
      unknown function, from 2-kb and 152-bp noncoding upstream regions of genes, to
      investigate the discriminatory potential of 23 properties related to gene
      regulation and population genetics. Among the most important properties detected
      in this region are distance to transcription start site, local repetitive
      content, sequence conservation, minor and derived allele frequencies, and
      presence of a CpG island. We further used the entire set of properties to
      evaluate their collective performance in detecting regulatory polymorphisms.
      Using a 10-fold cross-validation approach, we were able to achieve a sensitivity
      and specificity of 0.82 and 0.71, respectively, and we show that this performance
      is strongly influenced by the distance to the transcription start site.

PMID- 17559299
TI  - A mass conserved reaction-diffusion system captures properties of cell polarity.
AB  - Cell polarity is a general cellular process that can be seen in various cell
      types such as migrating neutrophils and Dictyostelium cells. The Rho small
      GTP(guanosine 5'-tri phosphate)ases have been shown to regulate cell polarity;
      however, its mechanism of emergence has yet to be clarified. We first developed a
      reaction-diffusion model of the Rho GTPases, which exhibits switch-like
      reversible response to a gradient of extracellular signals, exclusive
      accumulation of Cdc42 and Rac, or RhoA at the maximal or minimal intensity of the
      signal, respectively, and tracking of changes of a signal gradient by the
      polarized peak. The previous cell polarity models proposed by Subramanian and
      Narang show similar behaviors to our Rho GTPase model, despite the difference in
      molecular networks. This led us to compare these models, and we found that these
      models commonly share instability and a mass conservation of components. Based on
      these common properties, we developed conceptual models of a mass conserved
      reaction-diffusion system with diffusion-driven instability. These conceptual
      models retained similar behaviors of cell polarity in the Rho GTPase model. Using
      these models, we numerically and analytically found that multiple polarized peaks
      are unstable, resulting in a single stable peak (uniqueness of axis), and that
      sensitivity toward changes of a signal gradient is specifically restricted at the
      polarized peak (localized sensitivity). Although molecular networks may differ
      from one cell type to another, the behaviors of cell polarity in migrating cells
      seem similar, suggesting that there should be a fundamental principle. Thus, we
      propose that a mass conserved reaction-diffusion system with diffusion-driven
      instability is one of such principles of cell polarity.

PMID- 17559300
TI  - Modeling systems-level regulation of host immune responses.
AB  - Many pathogens are able to manipulate the signaling pathways responsible for the
      generation of host immune responses. Here we examine and model a respiratory
      infection system in which disruption of host immune functions or of bacterial
      factors changes the dynamics of the infection. We synthesize the network of
      interactions between host immune components and two closely related bacteria in
      the genus Bordetellae. We incorporate existing experimental information on the
      timing of immune regulatory events into a discrete dynamic model, and verify the
      model by comparing the effects of simulated disruptions to the experimental
      outcome of knockout mutations. Our model indicates that the infection time course
      of both Bordetellae can be separated into three distinct phases based on the most
      active immune processes. We compare and discuss the effect of the species
      specific virulence factors on disrupting the immune response during their
      infection of naive, antibody-treated, diseased, or convalescent hosts. Our model
      offers predictions regarding cytokine regulation, key immune components, and
      clearance of secondary infections; we experimentally validate two of these
      predictions. This type of modeling provides new insights into the virulence,
      pathogenesis, and host adaptation of disease-causing microorganisms and allows
      systems-level analysis that is not always possible using traditional methods.

PMID- 17559301
TI  - CpG island mapping by epigenome prediction.
AB  - CpG islands were originally identified by epigenetic and functional properties,
      namely, absence of DNA methylation and frequent promoter association. However,
      this concept was quickly replaced by simple DNA sequence criteria, which allowed
      for genome-wide annotation of CpG islands in the absence of large-scale
      epigenetic datasets. Although widely used, the current CpG island criteria incur
      significant disadvantages: (1) reliance on arbitrary threshold parameters that
      bear little biological justification, (2) failure to account for widespread
      heterogeneity among CpG islands, and (3) apparent lack of specificity when
      applied to the human genome. This study is driven by the idea that a quantitative
      score of "CpG island strength" that incorporates epigenetic and functional
      aspects can help resolve these issues. We construct an epigenome prediction
      pipeline that links the DNA sequence of CpG islands to their epigenetic states,
      including DNA methylation, histone modifications, and chromatin accessibility. By
      training support vector machines on epigenetic data for CpG islands on human
      Chromosomes 21 and 22, we identify informative DNA attributes that correlate with
      open versus compact chromatin structures. These DNA attributes are used to
      predict the epigenetic states of all CpG islands genome-wide. Combining
      predictions for multiple epigenetic features, we estimate the inherent CpG island
      strength for each CpG island in the human genome, i.e., its inherent tendency to
      exhibit an open and transcriptionally competent chromatin structure. We
      extensively validate our results on independent datasets, showing that the CpG
      island strength predictions are applicable and informative across different
      tissues and cell types, and we derive improved maps of predicted "bona fide" CpG
      islands. The mapping of CpG islands by epigenome prediction is conceptually
      superior to identifying CpG islands by widely used sequence criteria since it
      links CpG island detection to their characteristic epigenetic and functional
      states. And it is superior to purely experimental epigenome mapping for CpG
      island detection since it abstracts from specific properties that are limited to
      a single cell type or tissue. In addition, using computational epigenetics
      methods we could identify high correlation between the epigenome and
      characteristics of the DNA sequence, a finding which emphasizes the need for a
      better understanding of the mechanistic links between genome and epigenome.

PMID- 17559302
TI  - Epigenomic modifications predict active promoters and gene structure in
      Toxoplasma gondii.
AB  - Mechanisms of gene regulation are poorly understood in Apicomplexa, a phylum that
      encompasses deadly human pathogens like Plasmodium and Toxoplasma. Initial
      studies suggest that epigenetic phenomena, including histone modifications and
      chromatin remodeling, have a profound effect upon gene expression and expression
      of virulence traits. Using the model organism Toxoplasma gondii, we characterized
      the epigenetic organization and transcription patterns of a contiguous 1% of the
      T. gondii genome using custom oligonucleotide microarrays. We show that
      methylation and acetylation of histones H3 and H4 are landmarks of active
      promoters in T. gondii that allow us to deduce the position and directionality of
      gene promoters with >95% accuracy. These histone methylation and acetylation
      "activation" marks are strongly associated with gene expression. We also
      demonstrate that the pattern of histone H3 arginine methylation distinguishes
      certain promoters, illustrating the complexity of the histone modification
      machinery in Toxoplasma. By integrating epigenetic data, gene prediction
      analysis, and gene expression data from the tachyzoite stage, we illustrate
      feasibility of creating an epigenomic map of T. gondii tachyzoite gene
      expression. Further, we illustrate the utility of the epigenomic map to
      empirically and biologically annotate the genome and show that this approach
      enables identification of previously unknown genes. Thus, our epigenomics
      approach provides novel insights into regulation of gene expression in the
      Apicomplexa. In addition, with its compact genome, genetic tractability, and
      discrete life cycle stages, T. gondii provides an important new model to study
      the evolutionarily conserved components of the histone code.

PMID- 17559303
TI  - A molecular link between malaria and Epstein-Barr virus reactivation.
AB  - Although malaria and Epstein-Barr (EBV) infection are recognized cofactors in the
      genesis of endemic Burkitt lymphoma (BL), their relative contribution is not
      understood. BL, the most common paediatric cancer in equatorial Africa, is a high
      grade B cell lymphoma characterized by c-myc translocation. EBV is a ubiquitous B
      lymphotropic virus that persists in a latent state after primary infection, and
      in Africa, most children have sero-converted by 3 y of age. Malaria infection
      profoundly affects the B cell compartment, inducing polyclonal activation and
      hyper-gammaglobulinemia. We recently identified the cystein-rich inter-domain
      region 1alpha (CIDR1alpha) of the Plasmodium falciparum membrane protein 1 as a
      polyclonal B cell activator that preferentially activates the memory compartment,
      where EBV is known to persist. Here, we have addressed the mechanisms of
      interaction between CIDR1alpha and EBV in the context of B cells. We show that
      CIDR1alpha binds to the EBV-positive B cell line Akata and increases the number
      of cells switching to the viral lytic cycle as measured by green fluorescent
      protein (GFP) expression driven by a lytic promoter. The virus production in
      CIDR1alpha-exposed cultures was directly proportional to the number of GFP
      positive Akata cells (lytic EBV) and to the increased expression of the EBV lytic
      promoter BZLF1. Furthermore, CIDR1alpha stimulated the production of EBV in
      peripheral blood mononuclear cells derived from healthy donors and children with
      BL. Our results suggest that P. falciparum antigens such as CIDR1alpha can
      directly induce EBV reactivation during malaria infection that may increase the
      risk of BL development for children living in malaria-endemic areas. To our
      knowledge, this is the first report to show that a microbial protein can drive a
      latently infected B cell into EBV replication.

PMID- 17559304
TI  - Serogroup conversion of Vibrio cholerae in aquatic reservoirs.
AB  - The environmental reservoirs for Vibrio cholerae are natural aquatic habitats,
      where it colonizes the chitinous exoskeletons of copepod molts. Growth of V.
      cholerae on a chitin surface induces competence for natural transformation, a
      mechanism for intra-species gene exchange. The antigenically diverse O-serogroup
      determinants of V. cholerae are encoded by a genetically variable biosynthetic
      cluster of genes that is flanked on either side by chromosomal regions that are
      conserved between different serogroups. To determine whether this genomic motif
      and chitin-induced natural transformation might enable the exchange of serogroup
      specific gene clusters between different O serogroups of V. cholerae, a strain of
      V. cholerae O1 El Tor was co-cultured with a strain of V. cholerae O139 Bengal
      within a biofilm on the same chitin surface immersed in seawater, and O1-to-O139
      transformants were obtained. Serogroup conversion of the O1 recipient by the O139
      donor was demonstrated by comparative genomic hybridization, biochemical and
      serological characterization of the O-antigenic determinant, and resistance of O1
      to-O139 transformants to bacteriolysis by a virulent O1-specific phage. Serogroup
      conversion was shown to have occurred as a single-step exchange of large
      fragments of DNA. Crossovers were localized to regions of homology common to
      other V. cholerae serogroups that flank serogroup-specific encoding sequences.
      This result and the successful serogroup conversion of an O1 strain by O37
      genomic DNA indicate that chitin-induced natural transformation might be a common
      mechanism for serogroup conversion in aquatic habitats and for the emergence of
      V. cholerae variants that are better adapted for survival in environmental niches
      or more pathogenic for humans.

PMID- 17559305
TI  - Diversity in neuroanatomical distribution of abnormal prion protein in atypical
      scrapie.
AB  - Scrapie is a transmissible spongiform encephalopathy (TSE) in sheep and goats. In
      recent years, atypical scrapie cases were identified that differed from classical
      scrapie in the molecular characteristics of the disease-associated pathological
      prion protein (PrP(sc)). In this study, we analyze the molecular and
      neuropathological phenotype of nine Swiss TSE cases in sheep and goats. One sheep
      was identified as classical scrapie, whereas six sheep, as well as two goats,
      were classified as atypical scrapie. The latter revealed a uniform
      electrophoretic mobility pattern of the proteinase K-resistant core fragment of
      PrP(sc) distinct from classical scrapie regardless of the genotype, the species,
      and the neuroanatomical structure. Remarkably different types of neuroanatomical
      PrP(sc) distribution were observed in atypical scrapie cases by both western
      immunoblotting and immunohistochemistry. Our findings indicate that the
      biodiversity in atypical scrapie is larger than expected and thus impacts on
      current sampling and testing strategies in small ruminant TSE surveillance.

PMID- 17559306
TI  - A transcriptional program mediating entry into cellular quiescence.
AB  - The balance of quiescence and cell division is critical for tissue homeostasis
      and organismal health. Serum stimulation of fibroblasts is well studied as a
      classic model of entry into the cell division cycle, but the induction of
      cellular quiescence, such as by serum deprivation (SD), is much less understood.
      Here we show that SS and SD activate distinct early transcriptional responses
      genome-wide that converge on a late symmetric transcriptional program. Several
      serum deprivation early response genes (SDERGs), including the putative tumor
      suppressor genes SALL2 and MXI1, are required for cessation of DNA synthesis in
      response to SD and induction of additional SD genes. SDERGs are coordinately
      repressed in many types of human cancers compared to their normal counterparts,
      and repression of SDERGs predicts increased risk of cancer progression and death
      in human breast cancers. These results identify a gene expression program
      uniquely responsive to loss of growth factor signaling; members of SDERGs may
      constitute novel growth inhibitors that prevent cancer.

PMID- 17559309
TI  - Time for real action on chimpanzees and other hominids.

PMID- 17559307
TI  - Determinants of cell- and gene-specific transcriptional regulation by the
      glucocorticoid receptor.
AB  - The glucocorticoid receptor (GR) associates with glucocorticoid response elements
      (GREs) and regulates selective gene transcription in a cell-specific manner.
      Native GREs are typically thought to be composite elements that recruit GR as
      well as other regulatory factors into functional complexes. We assessed whether
      GR occupancy is commonly a limiting determinant of GRE function as well as the
      extent to which core GR binding sequences and GRE architecture are conserved at
      functional loci. We surveyed 100-kb regions surrounding each of 548 known or
      potentially glucocorticoid-responsive genes in A549 human lung cells for GR
      occupied GREs. We found that GR was bound in A549 cells predominately near genes
      responsive to glucocorticoids in those cells and not at genes regulated by GR in
      other cells. The GREs were positionally conserved at each responsive gene but
      across the set of responsive genes were distributed equally upstream and
      downstream of the transcription start sites, with 63% of them >10 kb from those
      sites. Strikingly, although the core GR binding sequences across the set of GREs
      varied extensively around a consensus, the precise sequence at an individual GRE
      was conserved across four mammalian species. Similarly, sequences flanking the
      core GR binding sites also varied among GREs but were conserved at individual
      GREs. We conclude that GR occupancy is a primary determinant of glucocorticoid
      responsiveness in A549 cells and that core GR binding sequences as well as GRE
      architecture likely harbor gene-specific regulatory information.

PMID- 17559310
TI  - Long-term, repeated dose in vitro neurotoxicity of the glutamate receptor
      antagonist L-AP3, demonstrated in rat hippocampal slice cultures by using
      continuous propidium iodide incubation.
AB  - Most in vitro models are only used to assess short-term effects of test
      compounds. However, as demonstrated here, hippocampal slice cultures can be used
      for long-term studies. The test compound used was the metabotropic glutamate
      receptor antagonist, L(+)-2-amino-3-phosphonopropionic acid (L-AP3), which is
      known to be toxic in vivo after subchronic, but not acute, administration.
      Degenerative effects were monitored by measuring the cellular uptake of propidium
      iodide (PI; continuously present in the medium) and lactate dehydrogenase (LDH)
      leakage, and by using a panel of histological stains. Hippocampal slices, derived
      from 2-3 day old rats and grown for 3 weeks, were subsequently exposed for the
      next 3 weeks to 0, 10 or 100microM L-AP3, with PI (2microM) in the culture
      medium. Exposure to 100microM L-AP3 induced severe toxicity after 4-6 days, shown
      by massive PI uptake, LDH leakage, changes in MAP2 and GFAP immunostaining, and
      in Nissl and Timm staining. In contrast, 10microM L-AP3 did not induce detectable
      neuronal degeneration. Treatment with the NMDA receptor antagonist, MK-801, or
      the AMPA/KA receptor antagonist NBQX, together with 100microM L-AP3, reduced
      neurodegeneration down to close to control values. It is concluded that
      continuous incubation of hippocampal slice cultures with PI is technically
      feasible for use in studies of inducible neuronal degeneration over time.

PMID- 17559308
TI  - Combined genome scans for body stature in 6,602 European twins: evidence for
      common Caucasian loci.
AB  - Twin cohorts provide a unique advantage for investigations of the role of
      genetics and environment in the etiology of variation in common complex traits by
      reducing the variance due to environment, age, and cohort differences. The
      GenomEUtwin (http://www.genomeutwin.org) consortium consists of eight twin
      cohorts (Australian, Danish, Dutch, Finnish, Italian, Norwegian, Swedish, and
      United Kingdom) with the total resource of hundreds of thousands of twin pairs.
      We performed quantitative trait locus (QTL) analysis of one of the most heritable
      human complex traits, adult stature (body height) using genome-wide scans
      performed for 3,817 families (8,450 individuals) derived from twin cohorts from
      Australia, Denmark, Finland, Netherlands, Sweden, and United Kingdom with an
      approximate ten-centimorgan microsatellite marker map. The marker maps for
      different studies differed and they were combined and related to the sequence
      positions using software developed by us, which is publicly available
      (https://apps.bioinfo.helsinki.fi/software/cartographer.aspx). Variance component
      linkage analysis was performed with age, sex, and country of origin as
      covariates. The covariate adjusted heritability was 81% for stature in the pooled
      dataset. We found evidence for a major QTL for human stature on 8q21.3
      (multipoint logarithm of the odds 3.28), and suggestive evidence for loci on
      Chromosomes X, 7, and 20. Some evidence of sex heterogeneity was found, however,
      no obvious female-specific QTLs emerged. Several cohorts contributed to the
      identified loci, suggesting an evolutionarily old genetic variant having effects
      on stature in European-based populations. To facilitate the genetic studies of
      stature we have also set up a website that lists all stature genome scans
      published and their most significant loci
      (http://www.genomeutwin.org/stature_gene_map.htm).

PMID- 17559311
TI  - Effects of the introduction of in vitro assays on the use of experimental animals
      in pharmacological research.
AB  - The introduction of in vitro assays in pharmacological research has led to a
      reduction in the number of experimental animals used. But what has been the
      degree of this reduction, and when did it really start? This report describes the
      events in a medium-sized pharmaceutical company. Analysis of data collected over
      the last 12 years shows a five-fold reduction in the number of experimental
      animals used per compound synthesised. Compounds from compound libraries (large
      collections of randomly-synthesised molecules) that are being assessed for
      potential bioactivity in 'high-throughput screening' were not included in this
      analysis. Over the years, the (average) degree of discomfort for the animals in
      the experiments did not vary much; with variation generally observed from 1.5 to
      2.0 (on a scale from 1-6). There was a peak in the discomfort score of
      experimental mice in 1997, which could be explained by the initiation of
      arthritis models that were subsequently refined, resulting in a lower degree of
      suffering. It might be concluded that the introduction of in vitro assays has
      indeed brought about a significant reduction in the number of experimental
      animals required to select a good compound (i.e. one that could progress to the
      preclinical toxicology phase). However, this development appears to have been
      neutralised by the low survival rate of new chemical entities in clinical
      studies, leading to a lower number of compounds per annum that actually reach the
      market place. Put in this 'productivity perspective', the number of experimental
      animals required to select a marketable drug has not much changed in the last
      decade.

PMID- 17559312
TI  - The Tubifex tubifex assay for the determination of acute toxicity.
AB  - An express (3-minute) test for acute toxicity determination by using the
      oligochaete annelid, Tubifex tubifex, is described. The EC50(Tubifex tubifex)
      [EC50(Tt)] for movement inhibition was calculated by using a concentration
      response dependence. The reproducibility of the test was checked over several
      years and by several workers. Its applicability is limited to compounds which are
      soluble in water. The calculated EC50(Tt) indices correlate with LC50 values
      determined by using the fish, Pimephales promelas (96-hour assay), and with ICG50
      values determined by using the ciliate, Tetrahymena pyriformis (48-hour assay)
      with high statistical significance (r = 0.822, n = 35, and r = 0.927, n = 80,
      respectively). The correlation between the EC50(Tt) indices and rat oral LD50
      values (48-hour assay) was r = 0.519 (n = 67). The correlation within organic
      compounds was closer (r = 0.635, n = 60) than with the heterogeneous series of
      chemicals. A similar trend was noticed for the correlation with mouse oral LD50
      values (r = 0.479, n = 56) with the heterogeneous series of chemicals, as
      compared that with the series without inorganic salts (r = 0.605, n = 42), and
      similarly with mouse intraperitoneal LD50 values, where r = 0.543 (n = 50) with
      the heterogeneous series of chemicals and r = 0.893 (n = 33) with the series of
      organic chemicals.

PMID- 17559313
TI  - The new EU REACH regulation has finally been adopted: is this the end of the
      campaign trail... or just the beginning?
AB  - The final EU REACH legislation has recently been adopted. This article considers
      the progress that has been made toward reducing the numbers of animals likely to
      be required to fulfil the testing requirements, and also considers the benefits
      to animal welfare and science that have arisen since the original REACH system
      proposals were published in 2003. Several positive changes have been made,
      including: the use of exposure-based testing; the requirement for scientific
      justification of any proposed animal testing; mandatory data sharing; and the
      fact that the EU is to take responsibility for the development and validation of
      alternative methods. While these changes are to be commended, there is still much
      room for improvement, particularly with respect to the adoption of integrated
      testing strategies that make maximum use of non-animal approaches to expedite the
      risk assessment process of existing chemicals, with the use of refined and
      updated animal tests only as a last resort.

PMID- 17559314
TI  - Chemical respiratory allergy: opportunities for hazard identification and
      characterisation. The report and recommendations of ECVAM workshop 60.

PMID- 17559315
TI  - Proposed integrated decision-tree testing strategies for mutagenicity and
      carcinogenicity in relation to the EU REACH legislation.
AB  - Liverpool John Moores University and FRAME recently conducted a research project
      sponsored by Defra, on the status of alternatives to animal testing with regard
      to the European Union REACH (Registration, Evaluation and Authorisation of
      Chemicals) system for the safety testing and risk assessment of chemicals. The
      project covered all the main toxicity endpoints associated with the REACH system.
      This paper focuses on the prospects for using alternative methods (both in vitro
      and in silico) for mutagenicity (genotoxicity) and carcinogenicity testing - two
      toxicity endpoints, which, together with reproductive toxicity, are of pivotal
      importance for the REACH system. The manuscript critically discusses well
      established testing approaches, and in particular, the requirement for short-term
      in vivo tests for confirming positive mutagenicity, and the need for the rodent
      bioassay for detecting non-genotoxic carcinogens. Recently-proposed testing
      strategies focusing on non-animal approaches are also considered, and our own
      testing scheme is presented and supported with background information. This
      scheme makes maximum use of pre-existing data, computer (in silico) and in vitro
      methods, with weight-of-evidence assessments at each major stage. The need for
      the improvement of in vitro methods, to reduce the generation of false-positive
      results, is also discussed. Lastly, ways in which reduction and refinement
      measures can be used are also considered, and some recommendations are made for
      future research to facilitate the implementation of the proposed testing scheme.

PMID- 17559316
TI  - Why 'suitable' in vitro methods, as defined in the final EU REACH legislation,
      are an inappropriate basis for risk assessment.
AB  - The final text of the REACH legislation, that has recently been published by the
      European Parliament, and which will come into force in the middle of 2007,
      implies that results obtained from so-called 'suitable' in vitro methods could be
      used for testing. It is also stated that a 'suitable' test is one that has been
      deemed to be ready to enter a validation study - for example, according to
      criteria specified by ECVAM. It is argued that, because the wording of the legal
      text is too vague and imprecise, it is totally unsatisfactory, mainly because it
      seems to endorse the application of non-validated methods for regulatory risk
      assessment. While their use might be suitable for providing information for
      classification in a weight-of-evidence approach, setting safe dose levels should
      only ever be based on the use of data from a properly validated test method. This
      concern, and other problems raised by the final legislation, is discussed, and
      recommendations are made which could avoid the premature use of potentially
      unsuitable methods for risk assessment, whilst ensuring that potentially suitable
      tests can be used for this purpose, once they have been formally validated.

PMID- 17559317
TI  - In vivo imaging shows abnormal function of vascular endothelial growth factor
      induced vasculature.
AB  - Although the angiogenic effect of vascular endothelial growth factor (VEGF) is
      widely recognized, a central question concerns whether the vessels formed on its
      overexpression effectively increase tissue perfusion in vivo. To explore this
      issue, here we exploit AAV vectors to obtain the prolonged expression of VEGF and
      angiopoietin-1 (Ang1) in rat skeletal muscle. Over a period of 6 months, muscle
      blood flow (MBF) and vascular permeability were measured by positron emission
      tomography and single-photon emission computed tomography, respectively. All
      measurements were performed under resting conditions and after electrically
      induced muscle exercise. Despite the potent angiogenic effect of VEGF, documented
      by vessel counting and intravascular volume assessment, the expression of this
      factor did not improve resting MBF, and it even decreased perfusion after
      exercise. This deleterious effect was related to the formation of leaky vascular
      lacunae, which accounted for the occurrence of arteriovenous shunts that excluded
      the downstream microcirculation. These effects were significantly counteracted by
      the coinjection of VEGF and Ang1, which determined a marked increase in resting
      MBF and, most notably, a significant improvement after exercise that persisted
      over time. Taken together, these results challenge the effectiveness of VEGF as a
      sole factor to induce angiogenesis and suggest the use of factor combinations to
      achieve competent vessel formation.

PMID- 17559318
TI  - Environmental effects on the behavior of zoo-housed lions and tigers, with a case
      study of the effects of a visual barrier on pacing.
AB  - Tigers and lions in the wild are nocturnal nonhuman animals who may hunt and mate
      opportunistically during daylight hours. In captivity, they spend most time on
      exhibit sleeping or pacing. To better understand their activity budget, this
      study examined the daily behavior patterns of 2 Sumatran tigers and 3 African
      lions in different housings. The proportion of scans the large felids spent
      engaged in stereotypic pacing varied by time of day and environment. The tigers
      spent different amounts of time pacing when housed in different exhibits; the
      lions paced more in off-exhibit housing than when on exhibit. These differences
      suggest changes to the cats' immediate housing environment may decrease pacing
      but provide little insight into altering specifics. Carnivores' pacing relates to
      their inability to control sensory access to social partners. Both environments
      with increased pacing contained chain-link fencing. allowing uncontrolled sensory
      contact. Where the tigers paced, the study placed a visual barrier between one
      female and keepers' or conspecifics' cues. This did not significantly decrease
      pacing. However, the study suggests considering sensory access and environmental
      variables when designing environments for captive carnivores.

PMID- 17559319
TI  - The influence of the location of a nest box in an individually ventilated cage on
      the preference of mice to use it.
AB  - The improvement of housing conditions for mice by using environmental enrichment
      materials is of high concern for the scientific community. Plastic, autoclavable
      nest boxes are commercially available and ready to use for specific cases such as
      in individually ventilated cages, metabolic cages, or during toxicological
      studies. The aim of this study was to see if the location of the nest box within
      the cage could influence the mice to prefer and use it. Located on the cage floor
      or hung from the cage lid, a nest box (MPLEX, Otto Environmental, Milwaukee,
      Wisconsin), enriched the cages. The study concluded that the location of the nest
      boxes in the individually ventilated cage plays a significant role in the mice
      preferring to use it or to avoid it. It is also important to use environmental
      enrichment items that provide animals with the possibility of expressing their
      preferences and manipulating them in a way to cope better with their
      environmental conditions.

PMID- 17559320
TI  - Combination therapy reduces self-injurious behavior in a chimpanzee (Pan
      Troglodytes Troglodytes): a case report.
AB  - Self-injurious behavior (SIB) remains a severe and intractable abnormal behavior
      for nonhuman primates in diverse settings and is a significant concern for
      veterinarians and behavioral scientists. To date, no single pharmacological,
      behavioral, social, or environmental intervention method has emerged as a
      reliable permanent cure for treating SIB in all, or even most, individuals.
      Implementation and evaluation of a combination therapeutic approach to treating
      SIB for nonhuman primates is rare. In May 2004, a 25-year-old male chimpanzee
      with severe SIB (M = 2.09 episodes/day, range = 1-4 episodes/day) underwent
      intensive behavioral intervention that utilized a combination of techniques. The
      combination therapy approach entailed the following: (a) pharmacological
      intervention with a gamma-aminobutyric acid (GABA) analogue to treat suspected
      HIV-related sensory neuropathic pain, (b) positive reinforcement training, and
      (c) environmental enrichment, as well as social and environmental modification.
      The severity of SIB warranted immediate implementation of intensive combination
      therapy rather than a systematic evaluation of the individual treatment options.
      The individually tailored, multifaceted combination therapy resulted in the
      virtual elimination of SIB in this chimpanzee over a 2-year period.

PMID- 17559321
TI  - Preliminary observations on the characteristics of the owned dog population in
      Roseau, Dominica.
AB  - This article reports findings from interviews with 93 heads of households (38.6%
      of all households) who owned 148 dogs in Roseau, the capital of The Commonwealth
      of Dominica. Mixed dogs, of no definable cross, were most common, followed by
      Rottweiler crosses. The median age of the dogs was 3 years, and 9.4% of the
      population was over 7 years. Respondents showed a definite preference for keeping
      male dogs (60%), and most animals were kept for protection (65%). Almost 30% of
      the dogs were allowed to roam. With 8.5% of the dogs neutered and 7 puppies per
      litter being born, the owned population produces more dogs than are required to
      maintain its size and so can provide recruits to the "stray" dog population.
      Comparisons with studies elsewhere in the Caribbean region (Fielding & Plumridge,
      2005; Ortega-Pacheco et al. (in press) suggest that environmental effects rather
      than the level of care offered are primarily responsible for controlling the dog
      population.

PMID- 17559322
TI  - Knowledge of the welfare of nonhuman animals and prevalence of dog care practices
      in New Providence, The Bahamas.
AB  - Interviews with 509 adults in New Providence, The Bahamas, indicated that people
      have limited knowledge of dog care and the laws pertaining to nonhuman animal
      welfare. Interviews also indicated that many dogs received care limited only to
      food and water and--to a lesser extent--shelter. Potcakes (local mongrels)
      received the least health care; "breed" dogs, the most. Primary caregivers gave
      the impression that dogs were better cared for than did nonprimary caregivers.
      Although some educational messages must distinguish between those who do--and do
      not--live in dog-keeping households, others need not. For example, myths
      associated with neutering are more deeply entrenched in the general population
      than within members of dog-keeping households. However, all respondents had an
      inadequate knowledge of the law relating to dog care.

PMID- 17559323
TI  - Visitors' effects on the welfare of animals in the zoo: a review.
AB  - Since the 1970s, research about zoo visitors' effects on the welfare of nonhuman
      animals in captivity has intensified. Numerous studies have shown that
      characteristics such as visitor presence, density, activity, size, and position
      are associated with animal behavioral and--to a lesser extent physiological-
      changes. Studies usually interpret these changes as negative (undesirable) or
      positive (enriching), but it remains unclear whether they significantly impinge
      on animal welfare. To make confident conclusions about visitors' effects
      necessitates more studies using (a) a wider range of animal groupings, (b)
      measures of stress, (c) visitor-animal variables, and (d) other methodological
      improvements In the meantime, in addition to further research, individual zoos
      need to emphasize (a) monitoring the stress indicators of their captive animals,
      (b) observing visitor behavior, and (c) ensuring that staffs are aware of the
      "visitor effect" concept.

PMID- 17559324
TI  - Oral behaviors of beef steers in pen and pasture environments.
AB  - This study observed the behavioral characteristics of 122 steers in eight pens
      and 1,136 steers at six pastures. Nonhuman animals kept in pens performed less
      nutritive oral behaviors and more nonnutritive oral behaviors than animals kept
      at pasture. Although these could not be described as stereotypies, they did
      represent a replacement of nutritive oral behaviors by nonnutritive oral
      behaviors, rather than simply an increase in resting time. This could be
      indicative of a level of oral frustration. At pasture, there was a greater
      proportion of oral behaviors in animals with low pasture availability as compared
      to high availability, but this was an increase in nutritive oral behaviors rather
      than nonnutritive oral behaviors. Factors other than oral frustration--for
      example, rumen fill--probably drove this increase.

PMID- 17559325
TI  - Introduction.

PMID- 17559326
TI  - Electrophysiological evaluation of human brain development.
AB  - The complex development of the human brain during infancy can only be understood
      by convergent structural, functional, and behavioral measurements. The evaluation
      of event-related potentials (ERPs) is the most effective current way to look at
      infant brain function. ERP paradigms can be used to examine the simple
      transmission of sensory information to the cortex and the discrimination of this
      information within the cortex. The main developmental changes involve
      localization of function as the brain becomes tuned to the experienced world
      (related to synaptic pruning) and a speeding up of transmission as pathways
      become efficient (related to myelination). ERPs that occur in relation to
      different temporal aspects of a stimulus (onset-responses, offset-responses,
      sustained potentials and steady-state responses) and ERPs recorded at different
      stimulus rates may help track perceptual development from a temporal perspective.
      Particularly important in human development are the ERP changes that occur in the
      processing of speech sounds and human faces. At present, ERP studies can show
      differences between groups of subjects that can demonstrate developmental
      disorders or elucidate mechanisms of development. However, because of their
      variability, ERPs are less helpful in determining whether an individual infant is
      developing abnormally. Where possible, ERP measurements should be used in
      conjunction with behavioral tests so as to relate performance to mechanism, and
      with anatomical brain measurements to relate mechanism to structure.

PMID- 17559327
TI  - The influence of infant diet on early developmental changes in processing human
      voice speech stimuli: ERP variations in breast and milk formula-fed infants at 3
      and 6 months after birth.
AB  - The purpose of this investigation was to determine if processing of language
      stimuli during the first half year of life in breast-fed infants differs from
      that of formula-fed infants. This question was addressed by examining the brain
      event-related potentials of healthy infants receiving breast milk (n = 15) or
      milk-based formula (n = 18) recorded in response to consonant vowel syllables
      presented in an oddball paradigm. The same infants were studied when they were 3
      months and 6-months-old. The two groups were comparable on several measures
      relating to biological and home environment variables previously reported to
      influence development, including gestation period, birth weight, mother's IQ, and
      family socioeconomic status, and did not differ in weight or mental or motor
      development at the times of the visits. In general, ERP response features
      previously documented in studies of syllable processing in 3-6-month-old infants
      were observed in this study, including positive components at asymptotically
      equal to 190 msec (P1), asymptotically equal to 370 msec (P2), and asymptotically
      equal to 600 msec (P600), and negative components at asymptotically equal to 250
      msec (N250), asymptotically equal to 450 msec (N450), and a late, negative going
      slow wave between 655 and 995 msec (LSW). For both groups there were instances
      where specific components were either poorly defined, e.g., P1 and N250 to the
      infrequent syllable at 3 months, N450 and P600 to this syllable at both ages, or
      not present in many infants, e.g., the P600 to the frequent syllable at 6 months.
      These variations appeared to be related to individual differences in development
      or paradigm-related features, i.e., ISI and frequency of syllable occurrence.

PMID- 17559328
TI  - Breast-fed infants process speech differently from bottle-fed infants: evidence
      from neuroelectrophysiology.
AB  - Numerous studies report positive effects of breast-feeding on infant development.
      Such effects are apparent early in development as well as in later years.
      Recently, elements in breast milk, polyunsaturatred fatty acids (PUFAs), have
      been identified as having great potential for increasing nutritional benefits.
      PUFAs are long-chain fatty acids containing two or more double bonds. While some
      scientists are enthusiastic about the long-term benefits of PUFAs on brain and
      cognitive development, many of the positive pharmacological effects attributed to
      PUFAs remain unsubstantiated. The present study investigated the differential
      impact of breast-feeding vs. PUFA-enriched formula in a small but well-matched
      population of 12 infants tested at 6 months of age. Event-related potential (ERP)
      and a range of behavior measures were recorded. ERP waveforms identified marked
      differences between the breast-fed and PUFA-fed infants by 6 months of age. When
      a range of biological, perinatal, and cognitive factors were equated between the
      two groups, only the ERPs recorded from breast-fed infants changed throughout
      their recorded period (700 msec), differentiated between all speech sounds, and
      generated differences in scalp recordings across all regions recorded across both
      hemispheres. Such differences in the range of their brain responses could signal
      an advantage for the breast-fed infants for later linguistic and cognitive
      development.

PMID- 17559329
TI  - Effects of breast milk and milk formula diets on synthesized speech sound-induced
      event-related potentials in 3- and 6-month-old infants.
AB  - Effects of breast milk and milk formula supplemented with docosahexaenoic acid
      and arachidonic acid on speech processing were investigated by recording event
      related potentials (ERPs) to synthesized /pa/ and /ba/ (oddball paradigm,
      80%:20%) at 3 and 6 months of age. Behavioral assessment was also obtained. A
      major positive component (P200) was elicited by both types of sounds. It had a
      maximal scalp distribution in the fronto-central areas in both groups of infants.
      The mean latencies did not differ between the groups or between the stimulus
      types. However, the latencies decreased across age in both groups. The mean P200
      amplitude in the formula-fed infants was lower than that in the breast-fed
      infants, but the difference was not significant. The between-stimulus differences
      in frontal P200 amplitudes were positively correlated with the behavioral scores
      of Bayley Index of Infant Development. These data suggest that the processing of
      the present speech stimuli is not affected by the investigated diets in the early
      infancy.

PMID- 17559330
TI  - Principal component analyses and scalp distribution of the auditory P150-250 and
      N250-550 to speech contrasts in Mexican and American infants.
AB  - We report a Principal Component Analysis (PCA) and the scalp distribution of the
      normalized peak amplitude values for speech-related auditory Event-related
      Potentials (ERP) P150-250 and N250-550 in 7-, 11-, and 20-month-old American
      infants learning English and in 10-13-month-old Mexican infants learning Spanish.
      After assessing the infant auditory ERP P-N complex using PCA, we evaluated the
      topographic distribution of each of the discriminatory phases to native and non
      native CV-syllabic contrasts used in Spanish and English. We found that the first
      two Principal Components for each contrast type across ages showing a
      maximization of differences between the P150-250 and the N250-550 waves, explain
      more than 70% of the variance. The scalp distributions of the P150-250 and N250
      550 components also differed, the P150-250 showing a frontal and anterior
      temporal distribution, and the N250-550 a more posterior distribution. The older
      infants showed a broader distribution of responses, particularly for the N250
      550. There were no differences in the topographies of the components between same
      aged Mexican and American infants. We discuss the perceptual/linguistic functions
      that each component may reflect during development and across the two cultures.

PMID- 17559332
TI  - Growth status related to brain responses, nutrition, home environment, and
      behavior in infants and toddlers.
AB  - To investigate whether growth status in infants and toddlers affects processes
      involved in speech perception and discrimination, cortical event-related
      potentials (ERPs) to consonant-vowel syllables were recorded from 48 healthy
      babies: 26 low in growth status (LGS, < 25 th percentile in growth measures) and
      from 22 normal in growth status (NGS, 25t--75 th percentile in growth measures).
      Food records indicated no significant differences in the amounts of various
      nutrients consumed in the two groups, but LGS babies consumed slightly more of
      most nutrients than NGS babies. In response to speech stimuli (either /pa/ or
      /ba/ presented with 20 and 80% randomized occurrence), brain ERPs showed two
      prominent post-stimulus components: a large positive wave peaking at about 484
      msec and a negative but positive going slow wave (SW) between 867 and 1199 msec.
      Principal components analysis followed by promax rotation revealed four
      additional important components. Maximum peak and latency values-for these
      components showed that NGS and LGS babies differed from one another on all
      measures in either amplitude, latency, or both. Comparing the two groups of
      babies, only the LGS group demonstrated a deficit in the phonetic discrimination
      of speech sounds. The growth deficiencies of the LGS group could not be
      attributed to the lack of an adequate diet. These negative findings are present
      in babies generally considered to be healthy (lowest 10-25% in growth measures).
      This underscores the need for research examining in more detail the relationship
      between growth status and cognitive growth.

PMID- 17559331
TI  - Using event-related potentials to study perinatal nutrition and brain development
      in infants of diabetic mothers.
AB  - Proper prenatal and postnatal nutrition is essential for optimal brain
      development and function. The early use of event-related potentials enables
      neuroscientists to study the development of cognitive function from birth and to
      evaluate the role of specific nutrients in development. Perinatal iron deficiency
      occurs in severely affected infants of diabetic mothers. In animal models, severe
      perinatal iron deficiency targets the explicit memory system of the brain. Cross
      sectional ERP studies have shown that infants of diabetic mothers have
      impairments in recognition memory from birth through 8 months of age. The purpose
      of this study was to evaluate longitudinal development of recognition memory
      using ERPs in infants of diabetic mothers compared with control infants. Infants
      of diabetic mothers were divided into high and low risk status based upon their
      birth weights and iron status and compared with healthy control infants. Infants
      were tested in the newborn period for auditory recognition memory, at 6 months
      for visual recognition memory and at 8 months for cross modal memory. ERPs were
      evaluated for developmental changes in the slow waves that are thought to reflect
      memory and the Nc component that is thought to reflect attention. The results of
      the study showed differences in development between the IDMs and control infants
      in the development of the slow waves over the left anterior temporal leads and
      age-related patterns of development in the NC component. These results are
      consistent with animal models showing that perinatal iron deficiency affects the
      development of the memory networks of the brain. This study highlights the value
      of using ERPs to translate basic science information obtained from animal models
      to the development of the human infant.

PMID- 17559333
TI  - Optimal digital filtering versus difference waves on the mismatch negativity in
      an uninterrupted sound paradigm.
AB  - Conventionally, mismatch negativity (MMN) is analyzed through the calculation of
      the difference waves. This helps to eliminate some exogenous event-related
      potential (ERP) components. However, this reduces the signal-to-noise ratio
      (SNR). This study aims to test whether or not the optimal digital filtering
      performs better than the difference waves procedure in quantitative ERP analyses
      in an uninterrupted sound paradigm. The participants were 102 children aged 8-16
      years. The MMN was elicited in a passive oddball paradigm presenting an
      uninterrupted sound consisting of two alternating tones (600 and 800 Hz) of the
      same duration (100 msec) with infrequent shortenings of one of the 600 Hz tones
      (50 or 30 msec). In the grand average, both the 50 and 30 msec tones showed a
      clear MMN-like activity. Each 100 msec tone elicited some rhythmic activity with
      relatively consistent ERP waveforms. The difference waves calculated from the
      offset of the deviant stimuli (time correction due to shortening of the deviant
      stimuli) failed to separate the MMN from this activity, and produced spurious
      ERPs at early latencies. The optimal digital filtering freed the MMN from this
      rhythmic activity, improved the SNR, and thus stabilized the quantitative
      amplitude and latency analyses of the MMN. The frequency range for optimal
      extraction of the MMN in this paradigm was 2-8.5 Hz.

PMID- 17559334
TI  - Does mismatch negativity show differences in reading-disabled children compared
      to normal children and children with attention deficit?
AB  - An auditory event-related potential (ERP) component called mismatch negativity
      (MMN) was examined in three groups of children (n = 63) aged 8-14 years. A
      control group comprised healthy children in second or sixth grade of
      comprehensive school (n = 21). The two clinical groups included children with
      reading disability (RD) (n = 21) and children with attention deficit (AD) (n =
      21). MMN was elicited in a passive oddball paradigm by duration changes in a
      continuous sound, consisting of two alternating (600 and 800 Hz) 100 msec tones.
      The deviant tones were either 30 or 50 msec in duration. Both deviants elicited a
      clear MMN in all groups. Statistical analyses showed no systematic difference in
      the MMN peak latencies or amplitudes between the groups. A significant difference
      between the RD group and the control group was observed in the lateralization of
      the MMN peak amplitudes.

PMID- 17559335
TI  - Dietary intake of elderly living in Toronto long-term care facilities: comparison
      to the dietary reference intake.
AB  - OBJECTIVE: To compare the dietary intake of elderly living in 11 long-term care
      facilities (LTCFs) to the Estimated Average Requirement set as part of the
      Dietary Reference Intake for older adults. DESIGN: A cross-sectional assessment
      of dietary intake using a 3 days food record among 407 elderly with mean age of
      85.2 +/- 7.7 years and BMI of 23.8 +/- 5.7 kg/m(2). This population sample was
      similar to the one living in LTCFs in the province of Ontario. RESULTS: The daily
      energy intake was 1513 +/- 363 kcal (6330.4 +/- 1518.8 kJ). Percentage of energy
      from fat, saturated fat, polyunsaturated fat, protein, and carbohydrate were 30%,
      11%, 5.2%, 15%, and 56%, respectively. Although these values were close to the
      recommendations, 29.5% had protein intake below the recommended 0.8 g/kg; and
      38.3% of subjects had cholesterol intake more than the recommended 300 mg/d. More
      than 50% of the subjects had suboptimal intake of calcium, magnesium, zinc and
      vitamins E, B(6), and folate. In addition, greater than 15% had suboptimal
      intakes of other micronutrients such as vitamins A, C, niacin, and copper.
      CONCLUSIONS: Elderly subjects living in LTCFs in Toronto despite having a normal
      body mass index (BMI), do not meet the recommended levels of intake for protein
      and many of the micronutrients. LTCFs staff should monitor dietary intake. Menu
      modification and micronutrient supplementation may be required in order to meet
      the daily requirements of these elderly.

PMID- 17559336
TI  - A model of metabolic changes in respiration-deficient human cells.
AB  - Cells lacking aerobic metabolism because of damaged mtDNA accumulate in many
      postmitotic tissues in the course aging. Although being only a small fraction of
      cells, they might play a major role in oxidative stress affecting the whole body.
      However, it remains unclear how such cells, which are under normal circumstances
      dependent on aerobic metabolism, are able to survive for decades in vivo. Here a
      new model is presented that proposes a coexistence of anaerobic glycolysis and a
      partly reversed TCA cycle. Succinate plays a key role in the changed metabolic
      pathways because it has to be exported by the cell. This hypothesis supports the
      view that some respiration-deficient cells are able to survive permanently within
      the body and contribute to human aging.

PMID- 17559337
TI  - Apolipoprotein E genotypic frequencies among Down syndrome patients imply early
      unsuccessful aging for ApoE4 carriers.
AB  - Down syndrome (DS) might be considered a model for unsuccessful and early aging,
      possibly accelerated for those who carry the APOE4 allele associated with common
      age-related diseases, e.g., Alzheimer's disease and a poor prognosis after acute
      myocardial infarction, causing lower ApoE4 frequencies among the very old in
      general populations. We compared ApoE genotypic frequencies found for healthy
      adults (n = 211, age < 40; n = 79, ages 70-79; n = 71, ages > 90) to those found
      for DS patients (n = 106, mean age 9 years), all living in western Sicily. We
      found that the frequency of the ApoE23 genotype increased with age among the
      healthy adults (8.5%, 6.4%, 19.7%; p = 0.024) while ApoE34 frequency decreased
      (16.1%, 12.6%, 4.1%; p = 0.012). DS patients had APOE34 genotypic frequencies
      very similar to those found in septuagenarians (9%; p = 0.005). Analyzing results
      according to surviving rate of persons with DS, an age-related reduction of
      ApoE3/4 genotype frequency was found comparing =5 years old to >5 years old DS
      subjects. These results highlight DS as a model to understand the role of APOE4
      allele in unsuccessful ageing considering that a number of proinflammatory
      supernumerary genes (Cu/Zn superoxide dismutase, Ets-2 transcription factors,
      Down syndrome critical region 1, stress-inducible factor, interferon-alpha
      receptor and the amyloid precursor protein) are located on chromosome 21 and are
      implied in the pathologic processes of DS.

PMID- 17559340
TI  - The sounds of silence: synonymous mutations affect function.

PMID- 17559341
TI  - More sensitive assays for better drug resistance prediction?

PMID- 17559342
TI  - Genetic engineering cures mice of neurological deficits: prospects for treating
      Angelman syndrome.

PMID- 17559344
TI  - Impact of CYP2B6 polymorphism on hepatic efavirenz metabolism in vitro.
AB  - OBJECTIVES: To determine the influence of cytochrome P450 2B6 (CYP2B6) genotype
      on the rate of oxidative efavirenz metabolism in human liver microsomes.
      MATERIALS & METHODS: Formation rates of 8-hydroxyefavirenz, 7-hydroxyefavirenz
      and 8,14-dihydroxyefavirenz were determined in vitro with efavirenz as a
      substrate (10 microM) in a large panel of human liver microsomes (n = 87) that
      were genotyped for variants of the CYP2B6 gene and phenotyped for CYP2B6 protein
      expression and bupropion hydroxylation. RESULTS: Efavirenz 8-hydroxylation, the
      major route of efavirenz clearance, was detected in all samples, exhibiting an
      overall interindividual variability of 44.7-fold; 8,14-dihydroxyefavirenz and 7
      hydroxyefavirenz were also detected in most samples. The formation rate of 8
      hydroxyefavirenz correlated significantly with CYP2B6 protein (Spearman's r(S) =
      0.54; p < 0.0001) and bupropion hydroxylase activity (r(S) = 0.73; p < 0.0001).
      Compared with the *1/*1 genotype, efavirenz 8-hydroxylation was significantly
      lower in samples with *1/*6 and *6/*6 genotype, which also had significantly
      decreased CYP2B6 protein (Mann-Whitney test, p < 0.05). A decrease in CYP2B6
      protein was also observed in samples with *1/*5 and *5/*6 genotypes, but this did
      not result in significant reduction of efavirenz metabolism, probably due to
      differences in specific activity of the protein variants. Lower CYP2B6 protein
      and activity, as well as efavirenz 8-hydroxylation was also found in several
      samples with rarer genotypes. We found no effect of gender and age on any of the
      phenotypes tested, but prior exposure to carbamazepine markedly increased CYP2B6
      protein expression and activity as well as efavirenz 8-hydroxylation.
      CONCLUSIONS: We have shown that CYP2B6 genetic polymorphism markedly influences
      the metabolism of efavirenz in human liver microsomes. Importantly, the CYP2B6*6
      allele harboring the SNPs c.516G>T [Q172H] and c.785A>G [K262R] was significantly
      associated with a pronounced decrease in CYP2B6 expression and activity, as well
      as a low rate of efavirenz 8-hydroxylation. These results represent a first step
      towards elucidating the mechanism by which this allele identifies patients
      exhibiting very high efavirenz plasma concentrations.

PMID- 17559345
TI  - Screening for SNPs and haplotypes in the CYP3A7 gene in Chinese populations.
AB  - OBJECTIVE: To determine the frequencies and haplotypes of the cytochrome P450
      (CYP)3A7 gene in three Chinese ethnic groups, namely, Han, She and Dong. METHODS:
      SNP analyses of the CYP3A7 gene were carried out on three groups of healthy
      Chinese subjects consisting of 539 Han, 264 She and 273 Dong subjects, using
      direct sequencing. Linkage disequilibrium, haplotype inference and Hardy-Weinberg
      equilibrium were also determined for these samples. RESULTS: Significant
      differences were observed in the distribution of SNP rs2257401 (CYP3A7*2), SNP
      1227 T>C (Novel), SNP rs4646468 and SNP rs10211 between the Han, She and Dong
      groups. CONCLUSION: Some allele and haplotype frequencies show variation among
      groups, highlighting the need to analyze clinically relevant SNPs and haplotypes
      in a variety of different racial groups within the Chinese population as well as
      in other ethnic groups. These results suggest that genetic polymorphisms in the
      CYP3A7 gene in the Han, She and Dong populations may contribute to
      interindividual as well as intra-ethnic differences in response to the clearance
      of CYP3A7 substrates.

PMID- 17559346
TI  - Novel SLC22A16 polymorphisms and influence on doxorubicin pharmacokinetics in
      Asian breast cancer patients.
AB  - OBJECTIVE: To identify novel polymorphisms in the solute carrier SLC22A16 gene
      and determine their influence on the pharmacokinetics of doxorubicin and
      doxorubicinol in Asian breast cancer patients. METHODS: SLC22A16 coding regions
      were screened in a total of 400 healthy subjects belonging to three distinct
      Asian ethnic groups (Chinese [n = 100], Malays [n = 100] and Indians [n = 100])
      and in the Caucasian population (n = 100). Pharmacokinetic parameters of
      doxorubicin and doxorubicinol were estimated in Asian breast cancer patients
      undergoing adjuvant chemotherapy to investigate genotype-phenotype correlations.
      RESULTS: Four novel polymorphisms (c.146A>G [exon 2], c.312T>C, c.755T>C [exon 4]
      and c.1226T>C [exon 5]) were identified. The genotypic frequency of the
      homozygous c.146GG polymorphism was approximately twofold higher in the healthy
      Chinese (13%) & Malay (18%) populations compared with the Indian (7%) and
      Caucasian (9%) populations. The genotypic frequency of the c.1226T>C polymorphism
      was observed to be significantly higher among the Caucasian (11%) and Indian (8%)
      study subjects compared with the Chinese (1%) and Malay (1%) ethnic groups (p <
      0.005 in each case). Breast cancer patients harboring the 146GG genotype showed a
      trend towards higher exposure levels to doxorubicin (AUC(0 negative
      infinity)/dose/body surface area [BSA] [hm(-5)]: 21.6; range: 18.8-27.7) compared
      with patients with either the reference genotype (AUC(0 negative
      infinity)/dose/BSA[hm(-5)]: 17.4; range: 8.2-26.3, p = 0.066) or heterozygotes
      (AUC(0 negative infinity)/dose/BSA[hm(-5)]: 15.4; range: 6.2-38.0, p = 0.055).
      The exposure levels of doxorubicinol were also higher in patients harboring the
      variant 146GG genotype (AUC(0 negative infinity)/dose/BSA[hm(-5)]: 13.3; range:
      8.8-21.7) when compared with patients harboring the reference genotype (AUC(0
      negative infinity)/dose/BSA[hm(-5)]): 9.8; range: 6.1-24.3, p = 0.137) or
      heterozygotes (AUC(0 negative infinity)/dose/BSA[hm(-5)]: 8.98; range: 3.7-20.6,
      p = 0.047). CONCLUSION: Among the four novel SLC22A16 polymorphisms identified,
      the c.146A>G and c.1226T>C polymorphisms exhibited interethnic variations in
      allele and genotype frequencies. This exploratory study suggests that the
      c.146A>G variation could contribute to the variations in the pharmacokinetics of
      doxorubicin and doxorubicinol in Asian cancer patients. Further in vitro studies
      are required to determine the functional impact of these novel polymorphisms on
      doxorubicin pharmacokinetics in cancer patients.

PMID- 17559347
TI  - Frequency of genetic polymorphisms of COX1, GPIIIa and P2Y1 in a Chinese
      population and association with attenuated response to aspirin.
AB  - BACKGROUND: Aspirin is a frequently prescribed drug for primary and secondary
      prevention of myocardial infarction, stroke and cardiovascular death. However,
      aspirin resistance may affect up to 45% of the population. Little is known on the
      role of genetic factors that contribute to resistance or augmented response to
      aspirin in different human populations. METHODS: In a large sample of nonsmoker,
      medication-free healthy volunteers from mainland China (n = 323; age: 22.1 +/-
      2.0 years) (mean +/- standard deviation), we determined the frequency of
      polymorphisms in cyclooxygenase 1 (COX1) (A-842G and C50T), glycoprotein IIIa
      (GPIIIa) (PLA1/A2) and purinergic receptor P2Y (P2Y1) (C893T and A1622G) genes.
      These candidate genes were chosen on the basis of their impact on platelet
      physiology and aspirin mode of action. A four panel P2Y1 genotype-stratified
      sample of healthy volunteers (n = 24 in total), identified from the large study
      sample above, prospectively received a 100 mg daily oral dose of aspirin for 7
      days. We measured changes in platelet aggregation before and after aspirin
      treatment. As a comparison reference group, 6 out of 24 subjects in the
      prospective aspirin trial had the P2Y1 CT893/AG1622 genotype that displays a low
      frequency (<7%) in the Chinese population. RESULTS: COX1 A-842G, C50T and GPIIIa
      PLA1/A2 genetic polymorphisms were not observed in our sample from mainland
      China. Allele frequencies of P2Y1 893T and 1622G were 3.5 and 30.6%,
      respectively. The heterozygosity for the P2Y1 A1622G polymorphism observed in the
      present study was different to Caucasians; Chinese displayed a higher allele
      frequency for the 1622G allele. After aspirin treatment, the net decrease in
      arachidonic acid-induced platelet aggregation was significantly larger in the
      P2Y1 CT893/AG1622 genotype panel (83.4 +/- 3.7%, net reduction by aspirin
      expressed as percentage of baseline) compared with CC893/GG1622 (68.2 +/- 13.5%),
      CC893/AG1622 (68.9 +/- 9.6%) and CC893/AA1622 (65.1 +/- 9.1%) genotypic groups (p
      = 0.012, 0.025 and 0.004, respectively; statistical power = 77%). There was no
      significant difference in antiplatelet effect of aspirin among the CC893/GG1622,
      CC893/AG1622 and CC893/AA1622 genotypes (p > 0.05). CONCLUSIONS: The COX1 A-842G,
      C50T and GPIIIa PLA1/A2 polymorphisms are rare in Chinese. In contrast to
      previous studies in Caucasian populations, these candidate functional
      polymorphisms are unlikely to be significant contributors to aspirin
      pharmacodynamics in Chinese persons. Importantly, the presence of the P2Y1 893CC
      genotype appears to confer an attenuated antiplatelet effect during aspirin
      treatment in healthy Chinese volunteers. These data collectively underscore the
      importance of population-to-population variability in clinical pharmacogenetics
      research and provide a basis for further long-term studies of aspirin response
      and P2Y1 genetic variation in patients with cardiovascular risk.

PMID- 17559348
TI  - Peroxisome proliferator-activated receptors as molecular targets in relation to
      obesity and type 2 diabetes.
AB  - The three isotypes of peroxisome proliferator-activated receptors (PPARs) are
      currently perceived as major regulatory nodes (or hubs) of metabolic pathway
      networks, linking most prevalent diseases including Type 2 diabetes, obesity,
      dyslipidemia and atherosclerosis. The integrative functions of PPARs are also
      reflected in their ecogenetic profile, when the variants underlying
      pharmacogenetic interactions were also shown to modulate the effect of lifestyle
      factors. Despite their extensive clinical use, there are many outstanding issues,
      especially concerning their safety. Critical pharmacogenomic assessment is
      warranted for the new potent ligands of multiple PPAR isoforms as many have
      displayed serious side-effects in a limited number of treated subjects.
      Nevertheless, the advent of genomic, transcriptomic and system biology-level
      approaches, integrating knowledge from model systems and human biology, should
      greatly facilitate the transition to individualized PPAR-based therapies.

PMID- 17559349
TI  - High-resolution DNA melting analysis for simple and efficient molecular
      diagnostics.
AB  - High-resolution melting of DNA is a simple solution for genotyping, mutation
      scanning and sequence matching. The melting profile of a PCR product depends on
      its GC content, length, sequence and heterozygosity and is best monitored with
      saturating dyes that fluoresce in the presence of double-stranded DNA. Genotyping
      of most variants is possible by the melting temperature of the PCR products,
      while all variants can be genotyped with unlabeled probes. Mutation scanning and
      sequence matching depend on sequence differences that result in heteroduplexes
      that change the shape of the melting curve. High-resolution DNA melting has
      several advantages over other genotyping and scanning methods, including an
      inexpensive closed tube format that is homogenous, accurate and rapid. Owing to
      its simplicity and speed, the method is a good fit for personalized medicine as a
      rapid, inexpensive method to predict therapeutic response.

PMID- 17559350
TI  - Pharmacogenetics of migraine: genetic variants and their potential role in
      migraine therapy.
AB  - Migraine is a paroxysmal neurological disorder affecting up to 6% of males and
      18% of females in the general population, and has been demonstrated to have a
      strong, but complex, genetic component. Genetic investigation of migraine
      provides hope that new targets for medications and individual specific therapy
      will be developed. The identification of polymorphisms or genetic biomarkers for
      disease susceptibility and treatment should aid in providing a better
      understanding of migraine pathology and, consequently, more appropriate and
      efficient treatment for migraineurs. In this review, we will discuss results
      investigating genetic biomarkers for migraine and their potential role in future
      therapy planning.

PMID- 17559351
TI  - ADME pathway approach for pharmacogenetic studies of anti-HIV therapy.
AB  - Pharmacogenetics holds promise in HIV treatment because of the complexity and
      potential toxicity of multidrug therapies that are prescribed for long periods.
      However, there has been limited success with the current approach where one or
      few candidate genes are examined for a limited number of allelic variants. A
      change in paradigm emerges from the availability of the HapMap, the wealth of
      data on less common genetic polymorphisms, and new genotyping technology. We
      present a comprehensive review of functional and putative functional variants in
      genes encoding absorption, distribution, metabolism and excretion (ADME) proteins
      relevant to HIV therapy. We propose an analytical array based on our review of
      the literature, web resources and use of bioinformatic analysis. We identified
      126 genes with proven or potential role in HIV therapy. Variation in these genes
      can be characterized by 2428 SNPs (in Caucasians). On average, a gene is covered
      by 20 SNPs. This review compiles information for future analysis of the role of
      specific genes/variants in the exposure and response to antiretroviral therapy to
      generate a ranked list of new genetic variants for future studies.

PMID- 17559352
TI  - Genetic polymorphisms of human flavin-containing monooxygenase 3: implications
      for drug metabolism and clinical perspectives.
AB  - Flavin-containing monooxygenase 3 (FMO3) is a hepatic microsomal enzyme that
      oxidizes a host of drugs, xenobiotics and other chemicals. Numerous variants in
      the gene encoding FMO3 have been identified, some of which result in altered
      enzymatic activity and, consequently, altered substrate metabolism. Studies also
      implicate individual and ethnic differences in the frequency of FMO3
      polymorphisms. In addition, new variants continue to be identified with
      potentially important clinical implications. For example, the role of FMO3
      variants in the pathophysiology of gastrointestinal diseases is an evolving area
      of research. Two commonly occurring polymorphisms of FMO3, E158K and E308G, have
      been associated with a reduction in polyp burden in patients with familial
      adenomatous polyposis who were treated with sulindac sulfide, an FMO3 substrate.
      These findings suggest a potential role for prospective genotyping of common FMO3
      polymorphisms in the treatment of disease states that involve the use of drugs
      metabolized by FMO3. This review summarizes the current state of research on the
      genetic polymorphisms of FMO3, with a focus on their clinical implications in
      gastrointestinal diseases.

PMID- 17559353
TI  - Genomic biomarkers, androgen pathway and prostate cancer.
AB  - Prostate cancer is the most frequent male malignancy diagnosed in western
      countries and the second leading cause of cancer-related deaths. The growth and
      function of the prostate gland depends on androgens. Owing to the importance of
      androgens in prostate development, genes involved in androgen biosynthesis and
      metabolism have been extensively studied. In this review, we address recent
      progress toward the use of inherited and acquired genetic variants to predict
      susceptibility and clinical outcomes of prostate cancer patients. Many of these
      genetic variants involve several genes related to the biosynthesis and metabolism
      of androgens, such as steroid-5-alpha-reductase, alpha polypeptide 2 (SRD5A2),
      cytochrome P450 (CYP)19A1, CYP17A1, hydroxy-delta-5-steroid dehydrogenase, 3 beta
      and steroid delta-isomerase 2 (HSD3B2) and androgen receptor (AR). With
      increasing knowledge, it may be possible to distinguish indolent from aggressive
      prostate tumors by molecular fingerprinting. Furthermore, with the emergence of
      new investigative tools, such as microarray platforms and comparative genomic
      hybridization (CGH) array, a variety of new genomic biomarkers will be available
      in the future to provide accurate prognostic and monitoring solutions for
      individualized patient care.

PMID- 17559354
TI  - Bruker Daltonics: leading the way from basic research to mass-spectrometry-based
      clinical applications.
AB  - For several years, Bruker Daltonics has been committed to the development of new
      applications of mass spectrometry in clinical research, which have the potential
      to become next-generation diagnostic procedures. After introducing the
      CLINPROTtrade mark product a couple of years ago, for biofluid analysis in the
      search of predictive peptide biomarkers indicating certain disease conditions,
      Bruker Daltonics recently expanded their portfolio with the MALDI BioTypertrade
      mark and the MALDI Molecular Imagertrade mark to enter new markets, such as the
      identification of microorganisms and molecular imaging. This article focuses on
      the current activities and future perspectives of these new clinical research
      solutions.

PMID- 17559355
TI  - Vita Genomics, Inc.
AB  - Vita Genomics, Inc., centered in Taiwan and China, aims to be a premier genomics
      based biotechnological and biopharmaceutical company in the Asia-Pacific region.
      The company focuses on conducting pharmacogenomics research, in vitro diagnosis
      product development and specialty contract research services in both genomics and
      pharmacogenomics fields. We are now initiating a drug rescue program designed to
      resurrect drugs that have failed in the previous clinical trials owing to low
      efficacies. This program applies pharmacogenomics approaches using biomarkers to
      screen subsets of patients who may respond better or avoid adverse responses to
      the test drugs. Vita Genomics, Inc. has envisioned itself as an important player
      in the healthcare industry offering advanced molecular diagnostic products and
      services, revolutionizing thedrug-development process and providing
      pharmacogenomic solutions.

PMID- 17559356
TI  - Relevance of ineffective esophageal motility and hyperactive acid sensitization
      in patients with gastroesophageal reflux.
AB  - BACKGROUND AND AIM: Esophageal motor abnormalities including ineffective
      esophageal motility (IEM) and visceral hypersensitivity have been frequently
      observed in patients with gastroesophageal reflux. The aim of this study was to
      observe the incidences of hypersensitivity to acid infusion and motor
      abnormalities in non-erosive reflux disease (NERD) compared with erosive
      esophagitis. METHODS: We performed upper GI endoscopy, an acid perfusion test and
      esophageal manometry on 113 NERD patients and 37 erosive esophagitis patients.
      RESULTS: The frequency of acid sensitization was 69.9% in NERD and 67.6% in
      erosive esophagitis. The frequency of esophageal motor abnormality in patients
      with erosive esophagitis (48.6%) was higher than in patients with NERD (25.7%, P
      = 0.014). The most frequent esophageal motor abnormality was IEM. The frequency
      of IEM was 15.9% in NERD patients, 42.9% in Los Angeles grade A, 53.8% in Los
      Angeles grade B and 66.7% in Los Angeles grade C esophagitis (chi(2) = 16.67, P <
      0.0001). CONCLUSION: Our results suggest that no difference exists between
      visceral hypersensitivity in patients with NERD and those with erosive
      esophagitis, and that IEM occurs in NERD as well as erosive esophagitis patients.
      The occurrence of IEM is associated with the endoscopic severity of
      gastroesophageal reflux disease.

PMID- 17559357
TI  - Lactose intolerance in patients with irritable bowel syndrome from northern
      India: a case-control study.
AB  - BACKGROUND AND AIM: Symptoms of irritable bowel syndrome (IBS) and lactose
      intolerance (LI) overlap. Data on the frequency of LI in patients with IBS from
      India are scanty. The aim of this study was to evaluate: (i) the frequency of LI
      in patients with IBS and its various subtypes as compared with healthy subjects
      (HS) from northern India; (ii) the relationship between self-reported milk
      intolerance and laboratory evidence of LI; and (iii) the role of small intestinal
      bacterial overgrowth in LI in patients with IBS. METHODS: 124 patients with IBS
      (Rome II criteria) and 53 age- and gender-matched HS were studied for LI using
      the lactose hydrogen breath test (LHBT) and the lactose tolerance test (LTT).
      Symptoms following lactose ingestion (diarrhea, bloating or distension) during
      the test and history of milk intolerance were recorded. Sixty-nine of the
      patients with IBS also underwent a glucose hydrogen breath test (GHBT). Patients
      with IBS were classified into those with diarrhea (IBS-D; >3 loose stools/d),
      constipation predominant (IBS-C; <3 stools/week) and indeterminate (IBS-I;
      between >or=3/week and <or= 3/d). RESULTS: 89/124 (72%) and 32/53 (60%, P = ns)
      IBS patients and HS were positive by LHBT and 82/124 (66%) and 38/53 (71%, P =
      ns) by LTT. Lactose intolerance as diagnosed either by LHBT or LTT was comparable
      among IBS patients and HS (102/124, 82% vs 41/53, 77%; P = ns). Peak breath
      hydrogen values during LHBT were also comparable among patients with IBS and HS
      (64 +/- 40 p.p.m. vs 61 +/- 44 p.p.m.). Patients with IBS developed symptoms
      following lactose ingestion more frequently than HS (68/124 vs 18/53, P = 0.01).
      Glucose hydrogen breath test was positive in 9/69 (13%) patients with IBS and was
      comparable among patients with (8/57, 14%) and without LI (1/12, 8%). Thirty had
      IBS-D whereas 94 had other subtypes of IBS (IBS-C, n = 9 and IBS-I, n = 85). The
      frequency of LI in IBS-D was similar to that of other subtypes (26/30, 86% vs
      76/94, 80%; P = ns). The positive and negative predictive value of self-reported
      milk intolerance in detecting LI was 81% and 23%, respectively. CONCLUSION: The
      frequency of LI is high and comparable among IBS patients and HS from northern
      India. Patients with IBS more often reported symptoms following lactose ingestion
      despite levels of breath hydrogen being similar to HS. The frequency of LI in
      patients with IBS-D was comparable to that in patients with other types of IBS.
      Self-reported milk intolerance has poor sensitivity in detecting LI.

PMID- 17559359
TI  - Comparison of three different second-line quadruple therapies including bismuth
      subcitrate in Turkish patients with non-ulcer dyspepsia who failed to eradicate
      Helicobacter pylori with a 14-day standard first-line therapy.
AB  - BACKGROUND AND AIM: Many studies have reported poor results with standard first
      line treatment for Helicobacter pylori. Second-line regimens that may overcome
      bacterial resistance can minimize side-effects and optimize compliance. The aim
      of this study was to evaluate the efficacy of proton pump inhibitor (PPI) and
      bismuth subcitrate-based quadruple therapy, after failure of a PPI plus
      clarithromycin and amoxicillin as first-line therapy. METHODS: Patients who
      failed to eradicate the infection after initial therapy were randomly separated
      into three groups. The first group received lansoprazole, bismuth subcitrate,
      metronidazole and amoxicillin (LBMA); in the second group metronidazole was
      replaced by tetracycline (LBTA); and the third group was given metronidazole and
      tetracycline in addition to same doses of lansoprazole and bismuth subcitrate
      (LBMT). RESULTS: In the LBMA group, the eradication rate was 74.7% and was
      significantly related to sex, with no relationship to age. In the LBTA group the
      eradication rate was 81.5% with similar rates in males and females. No relation
      to sex or age was observed. In the LBMT group the eradication rate was 82.1% with
      no difference between women and men and it was not related to age, either.
      Eradication rates in study groups were similar (P > 0.05). CONCLUSION: A-14-day
      regimen of lansoprazole, bismuth subcitrate and antibiotic pairs, tetracycline
      amoxicillin and tetracycline-metronidazole, is an effective quadruple therapy
      after one failed course of standard triple therapy. The evaluation of
      tolerability of and compliance with quadruple therapy needs further studies.

PMID- 17559358
TI  - Role of ISGF3 in modulating the anti-hepatitis B virus activity of interferon
      alpha in vitro.
AB  - BACKGROUND AND AIM: Although interferon-alpha (IFN-alpha) is an effective
      treatment for hepatitis B virus (HBV) infection, its precise mechanism of action
      has not been identified. In this study, we investigated the role of signal
      transduction pathways in the activation of anti-HBV responses mediated by IFN
      alpha. METHODS: Using an oligo microarray, we found that four genes in the IFN
      alpha signal pathway were markedly upregulated by IFN-alpha in human hepatoma
      cells regardless of whether they had been transfected with a plasmid containing
      the HBV genome: signal transducers and activators of transcription 1 (STAT1),
      interferon regulatory factor-9 (IRF-9, also called ISGF3gamma or P48), IFN-alpha
      inducible protein 15 (IFI-15) and IFN-alpha-inducible protein 6-16 (IFI-6-16). We
      also investigated the role of IFN-stimulated gene factor3 (ISGF3) complex in IFN
      alpha-mediated anti-HBV responses in human hepatoma cells by measuring the mRNA
      of the three genes within ISGF3 (STAT1, STAT2 and IRF-9) using semiquantitative
      reverse-transcription PCR (RT-PCR), and expression of the three proteins by
      western blot, and the mRNA and protein of dsRNA-dependent protein kinase (PKR).
      RESULTS: STAT1, STAT2, IRF-9 and PKR mRNA as well as protein levels were
      upregulated by IFN-alpha treatment. When cells were pretreated with genistein,
      STAT1, STAT2 and IRF-9 mRNA levels remained unchanged after IFN-alpha
      stimulation, but PKR mRNA levels decreased, and the expression of the STAT1, P
      STAT2, IRF-9 and PKR proteins decreased. Levels of HBV DNA decreased in the
      supernatants of cells treated with IFN-alpha, while ISGF3 levels increased. The
      quantity of HBV DNA remained unchanged by pretreating with genistein.
      CONCLUSIONS: These observations suggested that the Janus tyrosine kinase-STAT
      (JAK-STAT) pathway may play a major role in mediating the effects of IFN-alpha
      against HBV, and that ISGF3 might be a key factor.

PMID- 17559360
TI  - Helicobacter pylori eradication improves gastric histology and decreases serum
      gastrin, pepsinogen I and pepsinogen II levels in patients with duodenal ulcer.
AB  - BACKGROUND AND AIM: The aim of this study was to assess the gastric
      histopathology and serum gastrin-17 and pepsinogens profiles in patients with
      duodenal ulcer before and after Helicobacter pylori eradication in a population
      with a very high prevalence of H. pylori. At the same time we assessed the role
      of H. pylori density on these variables. METHODS: Eighty Caucasian patients with
      H. pylori-associated duodenal ulcer before treatment and 1 year after randomized
      eradication were studied. Among patients with unsuccessful eradication two groups
      were distinguished according to the data obtained after treatment: the group with
      negative rapid urease test and decreased bacterial density according to
      morphological score (partial elimination group); the group with positive rapid
      urease test and high bacterial density (failed eradication group). RESULTS: One
      year after successful eradication, serum levels of gastrin-17, pepsinogen I and
      pepsinogen II decreased. Similar changes of serum pepsinogen I and pepsinogen II
      levels were observed in patients with partial elimination of H. pylori infection.
      In the group with successful eradication, inflammation, activity, atrophy and
      number of lymphoid follicles in the antral mucosa fell. In the group with partial
      elimination, antral mucosa activity and H. pylori score reduced. Other
      morphological changes were statistically non-significant. CONCLUSION: Patients
      with duodenal ulcer after successful eradication have improvement of
      morphological and functional characteristics of gastric mucosa.

PMID- 17559361
TI  - Hypoxia and hepatocellular carcinoma: The therapeutic target for hepatocellular
      carcinoma.
AB  - Hypoxia enhances proliferation, angiogenesis, metastasis, chemoresistance, and
      radioresistance of hepatocellular carcinoma (HCC); suppresses differentiation and
      apoptosis of HCC; and consequently leads to resistance of transarterial
      embolization (with or without chemotherapy). Because transarterial embolization
      contributes to angiogenesis via inducing hypoxia, therapy combined with
      transarterial embolization and antiangiogenic therapy provides a new strategy for
      the treatment of HCC. Unfortunately, hypoxia leads to the escape of HCC cells
      from transarterial embolization and antiangiogenic therapy. Thus combined therapy
      that induces and targets hypoxia may be of benefit to HCC patients. Because
      angiogenesis plays an important role in recurrence of HCC after resection,
      antiangiogenic therapy is beneficial to HCC patients following surgical resection
      of the tumor.

PMID- 17559362
TI  - Improvement of the survival rate after rat massive hepatectomy due to the
      reduction of apoptosis by caspase inhibitor.
AB  - BACKGROUND AND AIM: Acute liver failure after massive hepatectomy is caused by
      both necrosis and apoptosis in the remnant liver. We investigate the protective
      effect of the caspase inhibitor on apoptosis after massive hepatectomy in rats.
      METHODS: Benzyloxycarbonyl-Val-Ala-Asp(OMe)-fluoromethylketone (ZVAD-fmk) is a
      general inhibitor of the caspase. Male Wister rats weighing 200-300 g were
      divided into three groups: 90Hx group undergoing 90% hepatectomy, 95Hx group
      undergoing 95% hepatectomy, 95Hx + ZVAD group undergoing 95% hepatectomy and
      administration of ZVAD-fmk. The 7-day survival rate was studied, and the rats
      were sacrificed at the 1, 2, 3, 5, and 7th day after hepatectomy. The remnant
      liver tissues were stained with hematoxylin-eosin, and with proliferating cell
      nuclear antigen (PCNA) for evaluation of liver regeneration, and with TdT
      mediated dUTP-biotin nick end labeling (TUNEL) and in situ oligo ligation method
      (ISOL) for evaluation of apoptosis. RESULTS: The 7-day survival rates were 100%,
      0%, and 30%, in the 90Hx, 95Hx, and 95Hx + ZVAD groups, respectively. There was
      no significant difference in PCNA labeling index (LI) between the 95Hx and 95Hx +
      ZVAD groups. TUNEL and ISOL LI of 95Hx + ZVAD group were significantly lower than
      those of 95Hx group. Fatal liver failure after massive hepatectomy was
      characterized by more apoptosis and less mitosis of hepatocytes. ZVAD-fmk could
      significantly attenuate apoptosis of hepatocytes in the remnant liver and improve
      the survival rate after 95% hepatectomy in rats. CONCLUSION: Caspase inhibitors
      such as ZVAD-fmk may provide a new adjuvant therapy to treat liver failure after
      massive hepatectomy.

PMID- 17559363
TI  - Molecular regulation of hepatic expression of iron regulatory hormone hepcidin.
AB  - Iron is a micronutrient that is an essential component that drives many metabolic
      reactions. Too little iron leads to anemia and too much iron increases the
      oxidative stress of body tissues leading to inflammation, cell death, and system
      organ dysfunction, including cancer. Maintaining normal iron balance is achieved
      by rigorous control of the amount absorbed by the intestine, that released from
      macrophages following erythrophagocytosis of effete red cells and by either
      release or uptake from hepatocytes. Hepcidin is a recently characterized molecule
      that appears to play a key role in the regulation of iron efflux from
      enterocytes, macrophages, and hepatocytes. It is produced by hepatocytes under
      basal conditions, in response to alterations in increased iron stores or reduced
      requirement for erythropoiesis and by inflammation. The proteins that regulate
      hepcidin expression are presently being defined, albeit that our present
      understanding is still far from complete. This review focuses on the molecules
      which regulate hepcidin expression. The subsequent characterization of these
      proteins using molecular, cellular, and physiological approaches also is
      discussed along with inflammatory signals and receptors involved in hepcidin
      expression.

PMID- 17559364
TI  - Effect of vasoactive intestinal peptide on gastric adenocarcinoma.
AB  - BACKGROUND AND AIM: Vasoactive intestinal peptide (VIP) is a gastrointestinal
      hormone in the secretin-VIP family. It has been reported that VIP affects some
      tumor growth, and there is a VIP autocrine regulation in some cancers. However,
      the effect of VIP on gastric adenocarcinoma is not clear yet. The aim of the
      present study was to investigate the effect of VIP on gastric adenocarcinoma,
      especially autocrine regulation of VIP on gastric adenocarcinoma. METHODS: VIP
      mRNA and protein, and its receptor mRNA (VIPR(1) and VIPR(2)) were measured in 15
      normal antrum mucosa, 20 gastric adenocarcinoma tissues, and the SGC7901 gastric
      adenocarcinoma cell line by using reverse transcription polymerase chain reaction
      (RT-PCR), immunohistochemistry, or radioimmunoassay methods. The effect of the
      VIP protein and its antagonist (D-p-Cl-Phe6, Leu17)-VIP on SGC7901 cell growth
      was detected by methylthiazolyldiphenyl-tetrazolium bromide (MTT) method. The
      expressions of c-myc mRNA and ornithine decarboxylase (ODC) mRNA in SGC7901 cells
      before and after the incubated VIP protein and/or its antagonist were also
      measured by RT-PCR method. RESULTS: The VIP mRNA expression in gastric
      adenocarcinoma tissues was significantly higher than that in normal antrum mucosa
      (P < 0.01). The VIP-positive immunoreactivity cells existed in 40% of gastric
      adenocarcinoma tissues, but not in normal tissues (P < 0.01). The VIP-positive
      immunoreactivity nerve fibers were observed in normal tissues, but not in
      adenocarcinoma tissues (P < 0.01). The expression rate of VIPR(1) mRNA in
      adenocarcinoma tissues was significantly lower than that in normal tissues, but
      that of VIPR(2) mRNA in the two kinds of tissues were similar (P > 0.05). In
      addition, the expression quantity of VIPR(1) mRNA and VIPR(2) mRNA in
      adenocarcinoma tissues was significantly lower than that in normal tissues (P <
      0.05). SGC7901 cells expressed not only VIP mRNA and the VIP protein, but also
      VIPR(1) and VIPR(2) mRNA. 10(6) SGC7901 cells secreted 13.15 +/- 8.54 pg VIP on
      average. VIP did not affect the proliferation of SGC7901 cells, but the
      antagonist stimulated the proliferation of SGC7901 cells from 10(-5) to 10(-8)
      mol/L concentration incubated for 24-96 h. VIP downregulated the expressions of c
      myc and ODC mRNA, but its antagonist upregulated their expressions. CONCLUSIONS:
      The expression of VIP mRNA upregulates, but the expressions of VIPR mRNA
      downregulates in gastric adenocarcinoma tissues. The gastric adenocarcinoma
      tissues contain endocrine cells to secrete VIP, which show malignant
      specialities. The VIP autocrine regulation exists in SGC7901 cells, and
      potentially inhibits the proliferation of the cells by downregulating the
      expressions of c-myc and ODC mRNA. It suggests that VIP may play an important
      role in the regulation of the growth of gastric cancer cells.

PMID- 17559365
TI  - Serrated neoplasias and de novo carcinomas in ulcerative colitis: a histological
      study in colectomy specimens.
AB  - BACKGROUND AND AIM: Cancer in ulcerative colitis (UC) originates in dysplastic
      crypts, adenomatous growths (UCAG), and UC-associated adenomas (UCAD). The aim of
      the present study was to compare the histological phenotypes between UCAG, UCAD,
      and sporadic colorectal adenomas in non-colitics (non-UCAD), as well as between
      UC-associated carcinomas (UCC) and carcinomas in non-colitic patients (non-UCC).
      METHODS: Three thousand and forty nine sections from 96 colectomy specimens in
      patients with UC-pancolitis and carcinoma were reviewed. RESULTS: Villous
      phenotypes were more frequent in UCAG (48%) than in UCAD (26%) and non-UCAD
      (11%), and serrated phenotypes more frequent in UCAD (29%) than in UCAG (12%) and
      non-UCAD (8%). Tubular phenotypes were far less frequent in UCAG (14%) than in
      UCAD (45%) and non-UCAD (80%). Villous and signet ring cell cancer phenotypes
      were more frequent in UCC (22% and 8%, respectively) than in non-UCC (9% and
      0.8%, respectively). Six UCC (5.6%) were de novo carcinomas. CONCLUSIONS:
      Invasive carcinomas were found in one-half of the UCAG and in one-third of the
      UCAD, indicating that both lesions are important in cancer development in UC. The
      different proportions of histological phenotypes found in UCAG, UCAD, and non
      UCAD on the one hand, and UCC and non-UCC on the other, suggest that chronic
      protracted inflammation might have modified the stem cell receptors that receive
      the molecular signals that program structural configurations in neoplastic
      glands. This is the first study reporting the occurrence of serrated and
      microtubular UCAG and of de novo carcinomas in UC.

PMID- 17559366
TI  - Elevated levels of serum advanced glycation end products in patients with non
      alcoholic steatohepatitis.
AB  - BACKGROUND AND AIM: Advanced glycation end products (AGE), senescent macroprotein
      derivatives formed at an accelerated rate in diabetes, play important roles in
      the pathogenesis of diabetic vascular complications. Recently, AGE have also been
      found to be involved in insulin resistance. Although non-alcoholic
      steatohepatitis (NASH) is generally considered a hepatic manifestation of insulin
      resistance, there are no reports showing the link of AGE to NASH. The aim of this
      study was to evaluate the clinical significance of AGE in patients with NASH.
      METHODS: Glyceraldehyde-derived AGE levels were assayed from serum obtained from
      106 patients: 66 with NASH, 10 with simple steatosis, and 30 controls. RESULTS:
      Serum glyceraldehyde-derived AGE levels (U/mL) were significantly elevated in
      NASH patients (9.78 +/- 3.73) compared with simple steatosis (7.17 +/- 2.28, P =
      0.018) or healthy controls (6.96 +/- 2.36, P = 0.003). Moreover, these were
      inversely correlated with adiponectin, an adipocytokine with insulin-sensitizing
      and anti-inflammatory properties. In addition, immunohistochemistry of
      glyceraldehyde-derived AGE showed intense staining in the livers of NASH
      patients. CONCLUSION: The present data suggest that the sustained increase of
      glyceraldehyde-derived AGE could at least in part contribute to the pathogenesis
      of NASH. The serum glyceraldehyde-derived AGE level may be a useful biomarker for
      discriminating NASH from simple steatosis.

PMID- 17559367
TI  - Norfloxacin and trimethoprim-sulfamethoxazole therapy have similar efficacy in
      prevention of spontaneous bacterial peritonitis.
AB  - BACKGROUND AND AIM: Although norfloxacin (N) is widely accepted as the drug of
      choice for spontaneous bacterial peritonitis (SBP) prophylaxis, there is data to
      suggest that trimethoprim-sulfamethoxazole (TS) may be similarly effective.
      However, no studies have compared the efficacy and safety of N and TS in SBP
      prophylaxis. The aim of this retrospective analysis was to compare outcomes in
      patients who received either N or TS for the prevention of SBP. METHODS: Records
      of all cirrhotic patients prescribed either N or TS for SBP prevention between
      April 2001 and May 2004 were reviewed. Data collected included age, sex, Child
      Pugh score, ascitic protein concentration, etiology of liver disease, infections
      (SBP, bacteremia, and extraperitoneal infections), side-effects, and survival.
      RESULTS: Sixty-nine patients (18 female, 51 male), mean age 53.9 +/- 10.6 years,
      were prescribed N (n = 37) or TS (n = 32). The Child-Pugh score, model for end
      stage liver disease score, and the prevalence of a low ascitic protein (<15 g/L)
      were similar between the groups (12.0 vs 12.4, 19.7 vs 18.2, and 78% vs 84%,
      respectively, P > 0.05). Fourteen (38%) infections occurred in the N group and 16
      (50%) in the TS group (P > 0.05). Eight patients (21.6%) in the N group and nine
      (28%) in the TS group developed SBP (P > 0.05). The rates of liver
      transplantation (10 vs 13), adverse events (two in each group) and death (13 vs
      14) were similar in the two treatment groups. CONCLUSIONS: Our findings suggest N
      and TS have similar efficacy in preventing SBP. This has significant implications
      for both the cost of SBP prophylaxis and the prevalence of fluoroquinolone
      resistance in patients with cirrhosis.

PMID- 17559368
TI  - Dyspepsia in HIV-infected patients under highly active antiretroviral therapy.
AB  - BACKGROUND AND AIM: Upper gastrointestinal symptoms, mainly dyspepsia, are common
      adverse effects in patients under highly active antiretroviral therapy (HAART).
      Whether it is worthwhile to perform endoscopy early in their treatment is a
      matter of debate. We have done a prospective study of the prevalence and the
      etiology of endoscopic lesions in a large cohort of dyspeptic adult HIV-infected
      patients under HAART, according to their immunological status. METHODS: 528 (334
      men and 194 women, mean age 38) HIV-infected patients under HAART with epigastric
      pain and/or nausea and vomiting underwent upper endoscopy. Patients were
      classified in two groups, according to CD4 cells counting (>200 cells/mm(3) or <
      or =200 cells/mm(3)). Gastric and duodenal biopsies were taken from normal mucosa
      and any lesion found. RESULTS: Gastric mucosa alterations were seen in 61.74% of
      patients (40.71% erythema, 18.38% erosion and 2.65% ulcer). Duodenum mucosa
      alterations were seen in 25.37% of patients, mainly erosions (19.50%) and ulcer
      (3.59%). There was no difference in endoscopic findings according to CD4 cell
      count groups. Chronic active gastritis was shown in 459 patients (86.93%). H.
      pylori infection was seen in 32.38%, and it was more prevalent in the group with
      CD4 > 200 (p < 0.01). Opportunistic infections and malignancies were seen
      exclusively in patients with CD4 < or = 200. CONCLUSIONS: Most of the endoscopic
      lesions in dyspeptic HIV-infected patients under HAART were not related to AIDS.
      Upper endoscopy was more helpful in dictating clinical treatment in patients with
      low CD4 counts (< or =200) and should be done earlier in this group.

PMID- 17559369
TI  - Efficacy of dioctahedral smectite in treating patients of diarrhea-predominant
      irritable bowel syndrome.
AB  - BACKGROUND AND AIM: Dioctahedral smectite (DS) is natural adsorbent clay useful
      in treating acute diarrhea. The aim of this study was to determine DS efficacy on
      patients with diarrhea-predominant irritable bowel syndrome (D-IBS in a phase III
      , 8-week-randomized, double-blind, placebo-controlled trial. METHODS: The 104
      patients who met the D-IBS Rome II criteria were randomized to receive either DS
      (n = 52) or placebo (n = 52) treatment for 8 weeks (three sachets daily). The
      primary efficacy endpoint was the changes of the visual analog scale (VAS) score
      of IBS overall disorder and pain/discomfort-related symptoms after treatment on
      days 28 and 56, respectively. Other outcome measures included improvement of
      bowel movement disorders. The therapeutic global response was assessed by the
      patients and investigators at each visit, as was drug safety. RESULTS: Both
      treatments diminished overall disorder at each visit (P < 0.01), with respect to
      primary efficacy. This effect was further observed in DS-treated patients on day
      56 (P = 0.0167). Placebo had no effect on the VAS score of pain/discomfort at any
      visit, whereas DS improved this score on days 28 and 56, respectively (P < 0.05).
      DS and placebo similarly diminished bowel disorders at each visit; however, only
      DS improved abdominal bloating (P < 0.01). The global therapeutic responses
      evaluated by the patients and investigators were similarly distributed. The study
      drug was well tolerated during the 8-week period. CONCLUSION: DS seems acceptable
      to treat D-IBS patients, particularly for pain-related symptoms.

PMID- 17559370
TI  - Possible involvement of cytokine gene polymorphisms in fulminant hepatitis.
AB  - BACKGROUND AND AIM: Host genetic factors have been reported as influencing the
      progress to fulminant hepatitis (FH). Our previous data showed the serum level of
      tumor necrosis factor (TNF)-alpha influenced by gene polymorphisms to be markedly
      increased. It was investigated whether polymorphisms in the IL-10 gene, in
      addition to TNF-alpha and -beta gene polymorphisms, might contribute to the
      pathogenesis of FH. METHODS: We analyzed 42 patients with FH, 78 patients with
      acute hepatitis (AH), and 149 healthy subjects (control). IL-10 polymorphism
      sites at promoter regions -1028, -819, -592; TNF-alpha polymorphism sites at
      promoter regions -1031, -863, -857, -308, -238; and TNF-beta first intron Nco1
      sites were studied. IL-10 gene polymorphisms were classified into three groups:
      low IL-10-producing haplotypes (ATA/ATA), intermediate haplotypes (ATA or
      CCA/CCA), and high haplotypes (ATA/ATG or CCG). RESULTS: The allelic frequency of
      B2 in the TNF-beta gene was significantly higher in FH patients compared with the
      control group. The three groups showed no differences in polymorphisms of
      positions -1031, -863, -857, -308 and -238 in the TNF-alpha gene. The frequency
      of low IL-10-producing haplotypes tended to be higher in FH patients compared
      with control and that of high IL-10-producing haplotype tended to be lower in FH
      patients compared with control. The carrier rate with both the IL-10 haplotype
      and the TNF-beta gene B2/B2 was significantly higher than control. CONCLUSION:
      Variations of cytokine polymorphisms including IL-10 and TNF-beta genes may be
      attributable to the pathogenesis of FH.

PMID- 17559371
TI  - Identification of a protective haplogenotype within CAPN10 gene influencing
      colorectal cancer susceptibility.
AB  - BACKGROUND AND AIM: Colorectal cancer (CRC) is one of the most prevalent types of
      cancer affecting both men and women in developed countries. Clinical and
      molecular evidence suggests that there are multiple biochemical pathways involved
      in its susceptibility, pathogenesis and prognosis. Several studies have reported
      a significant association between the incidence of CRC and type 2 diabetes
      mellitus (T2DM). However, genes associated with both conditions are rare. METHOD:
      We have analyzed the CAPN10 gene, a T2DM locus, using UCSNP-43, -44, -19, and -63
      markers, looking for differences between 371 CRC patients and 605 unrelated
      controls of Spanish origin. RESULTS: We found that UCSNP-44 allele C is swept out
      from cases (OR = 0.16, P = 0.005). Moreover, the frequency of 2111/2111
      haplogenotype is also statistically lower than expected in CRC patients (P =
      0.006). CONCLUSION: Taken together, our results indicate a recessive model for
      the effect of CAPN10 variant UCSNP-44 influencing the risk of CRC and suggest a
      novel genetic link between T2DM and colon carcinoma.

PMID- 17559372
TI  - Correlation between expression of leptin and clinicopathological features and
      prognosis in patients with gastric cancer.
AB  - BACKGROUND: The relationship between the expression of leptin in the tissue of
      gastric cancer and the clinicopathological features as well as patients' outcome
      were investigated. METHODS: Sixty-one gastric cancer specimens were investigated
      by immunohistochemical studies with anti-leptin and anti-vascular endothelial
      growth factor (VEGF) antibodies and by monitoring patients for at least 3 years
      after surgery. RESULTS: A positive rate of leptin expression was significantly
      associated with Borrmann classification (Borrmann type 1 and type 2 68.2% vs
      Borrmann type 3 and type 4 or unclassified 35.3%), tumor histology (well
      differentiated tumors 87.5% vs poorly differentiated tumors 48.9%), lymph node
      metastasis (with 69.0% vs without 36.8%) and stage (stage III + IV 69.0% vs stage
      I + II 36.8%). There was a significant association between leptin expression and
      VEGF expression. In the poorly differentiated group, the overall survival rate
      for patients with a weak expression of leptin (histochemistry score <0.5) was
      significantly higher than that in patients with a strong expression
      (histochemistry score =0.5). The Cox proportional hazards model identified
      serosal involvement, tumor size, metastasis, tumor histology, leptin expression,
      lymph node metastasis, age and postoperative chemotherapy as significant
      prognostic factors. CONCLUSIONS: The expression of leptin in the tissue of
      gastric cancer was significantly associated with tumor histology, Borrmann
      classification, lymph node metastasis and stage of gastric cancer. In patients
      with poorly differentiated gastric cancer, a poor prognosis was found in those
      with a strong expression of leptin.

PMID- 17559373
TI  - Prospective study of cardiac troponin I release in patients with upper
      gastrointestinal bleeding.
AB  - BACKGROUND AND AIM: The rate of cardiac injury in upper gastrointestinal
      hemorrhage is unclear. The aims of this study were to determine prospectively the
      risk of cardiac troponin I release and associated adverse cardiac events in
      patients with acute upper gastrointestinal hemorrhage. METHODS: From January to
      September 2003, we prospectively studied patients with documented hematemesis and
      melena referred to the gastroenterology unit in a tertiary teaching hospital in
      Melbourne, Australia. Serial assays for cardiac troponin I were performed at 0,
      12 and 24 h. Serial creatine kinase levels and electrocardiographs were also
      performed. Clinical and biochemical data were collected. The primary endpoint was
      a troponin level >0.5 microg/L within 24 h of recruitment. Various clinical
      variables were then compared between the groups of patients with or without
      troponin rise. RESULTS: A total of 156 patients were included in the study. The
      mean age was 67 years (range 19-96). There were 104 (67%) male patients. A
      troponin level of greater than 0.5 microg/L was found in 30/156 (19%); 126 (81%)
      patients had normal troponin levels. Age greater than 65 years, signs of
      hemodynamic instability at presentation, a recent history of cardiac disease,
      cardiovascular compromise following endoscopy, and re-bleeding were associated
      with troponin release. CONCLUSION: Upper gastrointestinal bleeding is associated
      with a risk of cardiac injury of up to 19%. Troponin assay could be used to
      screen for cardiac damage, especially in elderly patients who present with
      hemodynamic instability.

PMID- 17559374
TI  - Expression of MUC2 in gastric carcinomas and background mucosae.
AB  - BACKGROUND AND AIM: Gastric carcinomas contain elements of both intestinal and
      diffuse types. Such heterogeneous components may distort the evaluation of the
      role of the mucin MUC2 in gastric carcinoma. The role of MUC2 expression in
      background mucosa is not yet clarified. METHODS: We analyzed the expression of
      MUC2 in gastric mucosa and intestinal metaplasia adjacent to the tumoral area and
      carcinomas (n = 98) using immunohistochemistry. The immunoreactivity was
      quantified using an immunohistochemical scoring system. RESULTS: In the
      intestinal metaplasia adjacent to the tumoral area, MUC2 was detected in 76
      (97.4%) of 78 intestinal metaplasia, and MUC2 expression was inversely associated
      with the depth of wall penetration (P = 0.026) and tumor stage (P = 0.021).
      Although the expression rate of MUC2 antigens was higher in intestinal-type
      adenocarcinoma than in diffuse-type adenocarcinoma, a significant correlation
      with pathologic staging of the TNM system (pTNM staging) and MUC2 expression
      could not be found in each subtype of gastric carcinomas. CONCLUSION: The
      expression of MUC2 in intestinal metaplasia was higher in tumors of earlier
      stages. These findings suggest that increased MUC2 expression in intestinal
      metaplasia in the neighborhood of the carcinomas may play an important role in
      gastric carcinomas. Further investigations regarding the role of MUC2 expression
      in gastric carcinoma and background mucosae are necessary.

PMID- 17559375
TI  - Relationship between disease severity, quality of life and health-care resource
      use in a cross-section of Australian patients with Crohn's disease.
AB  - BACKGROUND AND AIM: New treatments for Crohn's disease are expensive and place
      economic strain upon health-care systems, and 'value-for-money' needs to be
      confirmed. This study aimed to correlate disease severity with health-related
      quality of life and with health-care resource use, to allow evaluation of the
      cost effectiveness of these treatments. METHODS: A cross-sectional, non
      interventional, pharmacoeconomics study was performed with patients completing
      questionnaires comprising demographic, disease and health-care utilization
      questions, together with the disease-specific Inflammatory Bowel Disease
      Questionnaire (IBDQ) and the Assessment of Quality of Life (AQoL) multi-attribute
      utility instrument. The Crohn's Disease Activity Index (CDAI) was used to assess
      disease severity. RESULTS: 143 patients with a broad range of disease severity
      (CDAI 36-446, fistulae 23%) were recruited from referral centers. Stepwise
      regression analyses demonstrated a negative correlation between disease severity
      and both IBDQ and AQoL (both P < 0.0001). Age, gender and years since diagnosis
      did not impact upon either of the quality-of-life outcomes. Mean utility score
      for non-fistulizing patients with moderate-severe active disease (CDAI >/= 220)
      was 0.45, mild disease (CDAI 150-219) was 0.68 and for remission (CDAI < 150) was
      0.77. Health-care resource utilization increased with increasing CDAI (P <
      0.001), with hospital admissions being the largest component cost. Twenty-seven
      percent of patients (mean age 38 year) received a government benefit, 51%
      primarily due to their Crohn's disease. CONCLUSION: Crohn's disease severity
      correlates with poor quality of life. Utility scores determined will permit cost
      utility analyses to be made in order to best allocate limited health resources.

PMID- 17559376
TI  - Somatostatin and gabexate for post-endoscopic retrograde cholangiopancreatography
      pancreatitis prevention: meta-analysis of randomized placebo-controlled trials.
AB  - BACKGROUND AND AIM: Prior studies have suggested the efficacy of somatostatin and
      gabexate in post-endoscopic retrograde cholangiopancreatography (ERCP)
      pancreatitis prevention. We examined this notion in our study. METHODS: An
      extensive literature search led to the inclusion of seven homogeneous high
      quality studies (Jadad score >or=4), involving 3,130 patients. The studies were
      grouped according to the drug's length of administration: given as an infusion
      for 12 h (groups SOM1 and GAB1 for somatostatin and gabexate, respectively);
      given as an infusion for less then 12 h (groups SOM2 and GAB2 for somatostatin
      and gabexate, respectively); and given as a bolus (group SOM3 for somatostatin,
      none identified for gabexate). Separate meta-analyses investigating post
      procedural pancreatitis and hyperamylasemia rates were conducted in a random
      effects model. RESULTS: Pancreatitis analyses yielded significant risk
      differences for the SOM1, SOM3 and GAB1 groups. The resulting values were 7.7%
      (95% confidence intervals [CI][3.4 to 12.0], P < 0.0001), 8.2% (95% CI [4.4 to
      12.0], P < 0.0001) and 5.2% (95% CI [1.1 to 9.4], P = 0.01), respectively. No
      statistically significant risk differences were observed for the SOM2 and GAB2
      groups: -2.3% (95% CI [-5.2 to 0.5], P = 0.11) and -1.1% (95% CI [-3.8 to 1.6], P
      = 0.41), respectively. Hyperamylasemia analyses yielded significant risk
      differences for the SOM1 and SOM3 groups (P = 0.017 and 0.001, respectively),
      although not for the SOM2, GAB1 and GAB2 groups (P = 0.44, 0.49 and 0.47,
      respectively). CONCLUSIONS: Somatostatin administered as a bolus seems to be an
      efficacious measure of post-ERCP pancreatitis prevention, reducing pancreatitis
      and hyperamylasemia rates, and being applicable to clinical practice. Further
      study is required before its introduction into routine care.

PMID- 17559377
TI  - A single center experience of methotrexate in the treatment of Crohn's disease
      and ulcerative colitis: a case for subcutaneous administration.
AB  - BACKGROUND AND AIM: Methotrexate (MTX) is used as a second-line immuno-modulator
      in patients with inflammatory bowel disease when purine analogs are not tolerated
      or lack efficacy. High-level evidence indicates efficacy for intramuscular
      administration in Crohn's disease, but there are few reports of experience with
      subcutaneous delivery. This study aimed to evaluate the response to and tolerance
      of MTX where subcutaneous administration was the preferred option. METHOD: The
      records of all patients treated with MTX were evaluated with regard to the dose,
      duration, response, and tolerance to MTX. Remission was defined as improvement in
      symptoms with no corticosteroid requirement for 3 months or ability to wean off
      steroids. RESULTS: MTX was initiated in 45 patients with Crohn's disease and 23
      ulcerative colitis (median age, 46 years; range, 20-80 years; 54% men) because of
      intolerance (69%) or resistance (31%) to purine analogues. MTX was initiated in
      74% of patients in doses of 25 mg (33) or 20 mg (17), administered by
      subcutaneous self-injection in 90% of subjects. Remission was achieved in 24 of
      45 (53%) with Crohn's disease and 11 of 23 (48%) with ulcerative colitis. An
      additional four (9%) patients with Crohn's disease and three patients (13%) with
      ulcerative colitis demonstrated symptomatic improvement and/or ability to
      decrease corticosteroid dose. While nine patients ceased therapy and nine
      successfully reduced their doses due to intolerance, three of four patients had
      no adverse effects. Subcutaneous delivery was well accepted. CONCLUSIONS:
      Subcutaneously administered MTX exhibits apparent efficacy, acceptance,
      tolerance, and safety in patients with Crohn's disease or ulcerative colitis who
      are steroid-dependent and where purine analogs have been ineffective or
      intolerable.

PMID- 17559378
TI  - New frontiers in capsule endoscopy.
AB  - Capsule endoscopy (CE) was launched at the beginning of this millennium and has
      since become a well-established tool for evaluating the entire small bowel for
      manifold pathologies. CE far exceeded our early expectations by providing us with
      a tool to establish the correct diagnosis for elusive gastrointestinal (GI)
      conditions such as obscure GI bleeding, Crohn's disease, polyposis syndrome, and
      others. Recent evidence has shown CE to be superior to other imaging modalities,
      such as small bowel follow-through X-ray, colonoscopy with ileoscopy,
      computerized tomographic enterography, magnetic resonance enteroclysis, and push
      enteroscopy, for diagnosing small bowel pathologies. Gastroenterologists would
      prefer the convenience of a single capsule that can create images of the area
      from the oral cavity to the anal canal in one 'shot'. Because of anatomic and
      physiologic differences in the GI tract, however, it may not be possible to use
      the same capsule and so we would need a different one for each organ. In addition
      to the pioneer small bowel capsule, there is now an esophageal capsule, and a
      colonoscopy capsule will soon be available. The ideal CE should be capable of
      performing a biopsy or carrying out an online analysis (an 'optical' biopsy) and
      'stop' bleeding by an epinephrine injection, a heat probe, argon plasma
      coagulation, etc. The ultimate capsule would include special detectors for white
      blood cells, and it would check oncological markers (e.g. CEA, CA 19-9), perform
      serology tests (e.g. antiendomysial, IgE), and measure various cytokines, pH
      levels, temperature and pressure, as well as deliver drugs. The capsule's
      motility feature in the small bowel may open a window to study the
      pathophysiology of relatively elusive medical entities, such as irritable bowel
      syndrome. The optimal capsule needs to contain an automatic computerized system
      for automatic detection of pathologies, such as that present in the ECG-Holter
      recording, in order to overcome the drawback of time-consuming viewing. Our dream
      is that endoscopists will be able to 'control and steer' the CE, as they are able
      to do in standard endoscopy. This would mean being able to maintain the capsule
      steady in a selected area and hold the view in order to have more time to examine
      the opposite wall of the bowel. In conclusion, future gastroenterologists will
      have a number of CEs from which to choose, according to the purpose of the
      evaluation, whether it be diagnostic and/or therapeutic. Just as the idea of a
      swallowed capsule taking images as it travels along the human anatomy was once in
      the realm of sheer fantasy, we have every reason to believe that the ultimate CE
      will become a reality in the not far distant future.

PMID- 17559379
TI  - Helicobacter pylori infection induces apoptosis in gastric cancer cells through
      the mitochondrial pathway.
AB  - BACKGROUND AND AIMS: To clarify the role of the mitochondrial pathway in
      apoptosis induced by H. pylori infection in gastric epithelial cells. METHODS:
      Cells of a gastric adenocarcinoma cell line SGC-7,901 were co-cultured with H.
      pylori NCTC 11,637, with or without preincubation with the inhibitors of caspases
      -3, -8, and -9. Apoptosis was determined by flow cytometry. RT-PCR was used to
      determine the expression of Bid, Bax, and Bcl-2 mRNA, and Western blotting was
      used to determine the expression of Bid, Bax, and Bcl-2 proteins, and the
      activation of caspases -3 and -9. RESULTS: H. pylori directly induced apoptosis
      in SGC-7,901 cells. Apoptotic indices (AIs) were 6.30 +/- 0.40%, 11.57 +/- 0.78%,
      8.63 +/- 0.67%, and 7.22 +/- 0.97%, respectively, at 6, 12, 24, and 48 h after
      SGC-7,901 cells were co-cultured with H. pylori. H. pylori up-regulated the
      expression of Bid and Bax at both protein and mRNA levels, and induced a time
      dependent activation of caspases -3 and -9. Apoptosis was inhibited significantly
      by the preincubation of SGC-7,901 cells with the inhibitors of caspase-3 (AIs
      were 1.72 +/- 0.59%, 2.97 +/- 0.55%, 4.38 +/- 1.56%, and 3.29 +/- 0.83%,
      respectively, at 6, 12, 24, and 48 h), and caspase -9 (AIs were 2.47 +/- 0.53%,
      6.68 +/- 0.47%, 5.97 +/- 0.46%, and 5.43 +/- 0.15%, respectively, at 6, 12, 24,
      and 48 h). The caspase-8 inhibitor also reduced H. pylori-induced apoptosis by
      20%. CONCLUSIONS: H. pylori infection induces apoptosis and the activation of
      caspases -3 and -9 in gastric cancer cells. Moreover, the caspase inhibitors
      significantly suppress H. pylori-induced apoptosis. These findings suggest that
      the mitochondrial pathway may be the major pathway in H. pylori-induced apoptosis
      in gastric epithelial cells.

PMID- 17559380
TI  - Influence of cytochrome P450 2C19 genetic polymorphism and dosage of rabeprazole
      on accuracy of proton-pump inhibitor testing in Chinese patients with
      gastroesophageal reflux disease.
AB  - BACKGROUND AND AIM: To evaluate the optimal dosage of rabeprazole for proton-pump
      inhibitor (PPI) testing of gastroesophageal reflux disease (GERD) and to test the
      influence of cytochrome P450 (CYP) 2C19 polymorphism in a population with a high
      prevalence of people who metabolize PPI poorly. METHODS: In this randomized, open
      label trial, patients with symptoms suggestive of GERD were randomized to receive
      a 2-week test with 20- or 40-mg rabeprazole after diagnostic endoscopy. Symptom
      response was assessed with a four-grade daily record; in addition, DNA from
      peripheral blood leukocytes was genotyped for CYP2C19 polymorphism with the
      polymerase chain reaction-restriction fragment length polymorphism technique.
      RESULTS: Of the 164 patients who completed the study, 69 (42.1%) were
      endoscopically positive for esophagitis; the remaining 95 (57.9%) were diagnosed
      with endoscopy-negative reflux disease. Based on the best cut-off value for 50%
      symptom reduction, the sensitivity, specificity, positive predictive value,
      negative predictive value, and accuracy for detecting erosive esophagitis were
      68%, 70%, 66%, 72%, and 69%, respectively, for the 20-mg regimen, and 84%, 71%,
      64%, 88%, and 76%, respectively, for the 40-mg regimen, a non-significant
      difference. Regarding the genotype, 60 (39%) patients had two wild-type alleles,
      63 (40.9%) had one variant allele, and 31 (20.1%) had two variant CYP2C19
      alleles. The presence of a variant allele did not alter the diagnostic efficacy
      of PPI testing. CONCLUSIONS: Both dose levels of rabeprazole proved efficacious
      in the diagnosis of GERD. Various measures of test accuracy were unrelated to the
      status of the CYP2C19 genotype.

PMID- 17559381
TI  - Risk factors analysis for hepatocellular carcinoma in patients with and without
      cirrhosis: a case-control study of 213 hepatocellular carcinoma patients from
      India.
AB  - AIM: To assess the role of hepatitis B virus (HBV), hepatitis C virus (HCV) and
      alcohol intake as risk factors for hepatocellular carcinoma (HCC) in the presence
      or absence of cirrhosis in Indian population. METHODS: A total of 213 patients
      with HCC and 254 control subjects not affected with hepatic diseases or neoplasm
      were recruited. Odds ratios (ORs) were estimated for each risk factor and
      synergism among various risk factors was also studied. RESULTS: The ORs and 95%
      confidence intervals (CI) of HCC were 48.02 (25.06-91.98) for any HBV marker,
      38.98 (19.55-77.71) for HBsAg positivity, 12.34 (2.84-53.61) for HBsAg negative
      and antibody positive (either of anti-HBe or total anti-HBc), 5.45 (2.02-14.71)
      for anti-HCV positive and HCV RNA positive, and 2.83 (1.51-5.28) for heavy
      alcohol use. No significant risk increase was evident for subjects who were anti
      HCV positive and HCV RNA negative. Synergism between alcohol and HCV infection in
      causing HCC was found, but not between alcohol and HBV. Overall, conclusive
      evidence of the presence or absence of cirrhosis was reached in 189 (88.73%) HCC
      patients; cirrhosis was present in 137 (72.48%) of them. ORs with 95% CI of HCC
      in the presence and absence of cirrhosis, respectively, for HBV were as follows:
      (i) 48.90 (24.61-97.19) and 35.03 (15.59-78.66) for any HBV marker; (ii) 39.88
      (19.41-81.97) and 24.40 (10.60-56.18) for HBsAg positivity; and (iii) 12.10 (2.67
      54.88) and 19.60 (3.94-97.39) for HBsAg negativity and antibody positivity.
      Significantly increased risk was found among cirrhotic patients for anti-HCV
      positivity and HCV RNA positivity [OR = 7.53 (2.73-20.78)] and for heavy alcohol
      use [OR = 3.32 (1.70-6.47)]; however, in the absence of cirrhosis, no significant
      risk increase was evident for subjects who were anti-HCV positive and HCV RNA
      positive [OR = 0.97 (0.11-8.54)], or who had history of heavy alcohol use [OR =
      1.58 (0.55-4.53)]. CONCLUSIONS: Infection with HBV and HCV are the major risk
      factors for the development of HCC in Indian patients. Presence of HBV antibodies
      even in the absence of HBsAg conferred increased risk for HCC in the presence or
      absence of cirrhosis. Anti-HCV positivity in the absence of HCV RNA conferred no
      increased risk. HCV RNA positivity and heavy alcohol use significantly increased
      the risk of HCC among cirrhotic patients, but not non-cirrhotic patients.

PMID- 17559382
TI  - Vascular targeting agent Oxi4503 inhibits tumor growth in a colorectal liver
      metastases model.
AB  - BACKGROUND AND AIM: Oxi4503 is a potent vascular targeting agent belonging to the
      family of combretastatins. These agents produce an acute reduction in tumor blood
      flow leading to tumor necrosis. Despite evidence of its efficacy in certain
      malignancies, the effect on colorectal liver metastases remains largely unknown.
      This study investigates the effect of Oxi4503 on colorectal liver metastases in a
      murine model. METHODS: The effect of a single dose of Oxi4503 on established
      tumors in a murine model of colorectal liver metastases was assessed following
      administration of 1-50 mg/kg Oxi4503. In addition, the effects of continuous,
      daily and intermittent dosing (1-5 mg/kg) on tumor necrosis and growth were
      studied by quantitative histological and stereological analysis. The effect of
      multiple dosing on long-term survival was also assessed using the Kaplan-Meier
      analysis. The microvascular effects of therapy were studied by scanning electron
      microscopy of microvascular resin casts. RESULTS: A single dose of 5 or 50 mg/kg
      of Oxi4503 produced significant tumor necrosis compared to the controls.
      Subcutaneous continuous dosing infusion with Oxi4503 at 1 mg/kg/day reduced tumor
      growth compared to the controls, but was associated with marked systemic
      toxicity. Daily administration over 21 days was associated with significant
      mortality. Intermittent dosing of Oxi4503 (two doses, 3 days apart) produced the
      greatest reduction in tumor growth with minimal toxicity and conferred a
      significant survival advantage. Microvascular casts demonstrated significant
      disruption of tumor vessels. CONCLUSIONS: A single dose of Oxi4503 produced
      significant necrosis and microvascular injury in colorectal liver metastases.
      Intermittent dosing with Oxi4503 produced the maximum reduction in tumor growth,
      minimal toxicity, and a significant improvement in survival. Oxi4503 is a
      potential anticancer agent. Further research into its mechanism of action and its
      synergistic use with other therapies is warranted.

PMID- 17559383
TI  - Correlation of hepatitis B core antigen and beta-catenin expression on
      hepatocytes in chronic hepatitis B virus infection: relevance to the severity of
      liver damage and viral replication.
AB  - BACKGROUND AND AIMS: The topographical distribution of hepatitis B core antigen
      (HBcAg) is related to the pathogenesis of liver damage caused by hepatitis B
      virus (HBV) infection. beta-catenin plays an important role in both intracellular
      adhesion and Wnt signaling transduction pathways. This study investigated the
      intrahepatic expression of HBcAg and beta-catenin in chronic HBV infection, and
      correlated the results with the degree of liver damage and viral replication.
      METHOD: Liver sections from 73 patients with chronic HBV infection were examined
      immunohistochemically for HBcAg and beta-catenin. RESULTS: The distribution of
      HBcAg could be classified into four types: only nucleus (C-1), both nucleus and
      cytoplasm (C-2), only cytoplasm (C-3) and all negative for nucleus and cytoplasm
      (C-4). Significant differences in serum aminotransferase level, HBV DNA and
      necroinflammatory score were observed among the different distribution types, and
      as the distribution of HBcAg changed from C-1 to C-4, fibrosis stage and
      hepatitis B e antigen (HBeAg) negative/anti-HBe positive rate increased
      concurrently. The distribution of beta-catenin could be classified into two
      types: only membrane (B-1) and membrane with nucleus or cytoplasm (B-2). B-2
      showed higher serum aminotransferase level and necroinflammatory score than B-1.
      Between B-1 and B-2, there was no significant difference in serum HBV DNA level
      or fibrosis stage. CONCLUSIONS: In chronic HBV infection, HBcAg distribution may
      change from C-1 to C-4 gradually, and in correlation with serum aminotransferase,
      and HBV DNA and HBeAg negative/anti-HBe positive rate. Nuclear or cytoplasmic
      distribution of beta-catenin, compared with exclusive membranous distribution of
      beta-catenin, is related to active hepatitis, but not viral replication.

PMID- 17559384
TI  - The long-term efficacy of Helicobacter pylori eradication therapy in patients
      with idiopathic thrombocytopenic purpura.
AB  - BACKGROUND AND AIM: A beneficial effect of Helicobacter pylori (H. pylori)
      eradication in patients with H. pylori-positive idiopathic thrombocytopenic
      purpura (ITP) has been reported by several investigators; however, it was not
      clear whether the recovered platelet count after H. pylori eradication was
      maintained for a long period. METHOD: Thirty-eight ITP patients who were examined
      for H. pylori infection were assessed. H. pylori-positive patients received a
      standard antibiotic therapy for H. pylori eradication. We investigated the long
      term effect of H. pylori eradication on platelet recovery in patients with H.
      pylori-positive ITP. RESULTS: Of the 38 ITP patients, 26 (68.4%) were positive
      for H. pylori. The response rate of platelet recovery was 56.5% (13/23 patients).
      Twelve patients showed complete response (CR) and one showed partial response
      (PR). The mean platelet counts 6 months after eradication significantly increased
      from 31 x 10(9)/L to 129 x 10(9)/L in 23 H. pylori-eradicated patients (P <
      0.001). The median platelet counts of responders 1, 2, 3, and 4 years after
      eradication were 168 x 10(9)/L (n = 10), 193 x 10(9)/L (n = 9), 168 x 10(9)/L (n
      = 7), and 243 x 10(9)/L (n = 4) after a mean follow-up of 25.8 months.
      CONCLUSION: Eradication therapy for H. pylori-positive patients with ITP was
      effective and a favorable effect was maintained for long periods.

PMID- 17559385
TI  - The 15-lipoxygenase-1 expression may enhance the sensitivity to non-steroidal
      anti-inflammatory drug-induced apoptosis in colorectal cancers from patients who
      are treated with the compounds.
AB  - BACKGROUND AND AIM: Non-steroidal anti-inflammatory drugs (NSAIDs) can prevent
      colorectal cancer (CRC), but their effect is limited. Recent studies have shown
      the involvement of 15-lipoxygenase-1 (15-LOX-1) in NSAID-induced apoptosis in
      colorectal carcinoma cells. We evaluate whether 15-LOX-1 expression influences
      the sensitivity of NSAID-induced apoptosis in CRCs. METHODS: In 22 CRC surgical
      samples from NSAID users who had been constant for more than 5 years and 28 CRC
      surgical samples from NSAID non-users, the expressions of 15-LOX-1,
      cyclooxygenase-2 (COX-2), beta-catenin, and p53 were analyzed using
      immunohistochemistry. TUNEL assay was also performed for samples. The effects of
      the transient transfection of 15-LOX-1 cDNA on indomethacin-induced apoptosis
      were certified in HCT-116 cells. The effects of adding 13-S-hydroxyoctadecadinoic
      acid (13-S-HODE) on indomethacin-induced apoptosis were also examined in HCT-116
      cells. The levels of apoptosis were determined by the analysis of the floating
      cells ratio and DNA gel electrophoresis. RESULTS: The expression of 15-LOX-1 on
      CRCs from NSAID users was significantly decreased compared with those from NSAID
      non-users; however, the expressions of other molecules were not significantly
      different between two groups. The levels of TUNEL scoring in samples from NSAID
      users were similar to those from NSAID non-users. Indomethacin (100 microM)
      induced less apoptosis in mocked cells, whereas the same concentrations of
      indomethacin enhanced the level of apoptosis in 15-LOX-1-transfected cells. 13-S
      HODE also increased the level of indomethacin-induced apoptosis in cells.
      CONCLUSION: Results suggest that 15-LOX-1 expression may be one of the mechanisms
      which enhance the sensitivity to NSAID-induced apoptosis in CRCs from patients
      who are treated with the compounds.

PMID- 17559386
TI  - Validation of computer simulation training for esophagogastroduodenoscopy: Pilot
      study.
AB  - BACKGROUND: Little is known regarding the value of esophagogastroduodenoscopy
      (EGD) simulators in education. The purpose of the present paper was to validate
      the use of computer simulation in novice EGD training. METHODS: In phase 1,
      expert endoscopists evaluated various aspects of simulation fidelity as compared
      to live endoscopy. Additionally, computer-recorded performance metrics were
      assessed by comparing the recorded scores from users of three different
      experience levels. In phase 2, the transfer of simulation-acquired skills to the
      clinical setting was assessed in a two-group, randomized pilot study. The setting
      was a large gastroenterology (GI) Fellowship training program; in phase 1, 21
      subjects (seven expert, intermediate and novice endoscopist), made up the three
      experience groups. In phase 2, eight novice GI fellows were involved in the two
      group, randomized portion of the study examining the transfer of simulation
      skills to the clinical setting. During the initial validation phase, each of the
      21 subjects completed two standardized EDG scenarios on a computer simulator and
      their performance scores were recorded for seven parameters. Following this,
      staff participants completed a questionnaire evaluating various aspects of the
      simulator's fidelity. Finally, four novice GI fellows were randomly assigned to
      receive 6 h of simulator-augmented training (SAT group) in EGD prior to beginning
      1 month of patient-based EGD training. The remaining fellows experienced 1 month
      of patient-based training alone (PBT group). Results of the seven measured
      performance parameters were compared between three groups of varying experience
      using a Wilcoxon ranked sum test. The staffs' simulator fidelity survey used a 7
      point Likert scale (1, very unrealistic; 4, neutral; 7, very realistic) for each
      of the parameters examined. During the second phase of this study, supervising
      staff rated both SAT and PBT fellows' patient-based performance daily. Scoring in
      each skill was completed using a 7-point Likert scale (1, strongly disagree; 4,
      neutral; 7, strongly agree). Median scores were compared between groups using the
      Wilcoxon ranked sum test. RESULTS: Staff evaluations of fidelity found that only
      two of the parameters examined (anatomy and scope maneuverability) had a
      significant degree of realism. The remaining areas were felt to be limited in
      their fidelity. Of the computer-recorded performance scores, only the novice
      group could be reliably identified from the other two experience groups. In the
      clinical application phase, the median Patient Discomfort ratings were superior
      in the PBT group (6; interquartile range [IQR], 5-6) as compared to the SAT group
      (5; IQR, 4-6; P = 0.015). PBT fellows' ratings were also superior in Sedation,
      Patient Discomfort, Independence and Competence during various phases of the
      evaluation. At no point were SAT fellows rated higher than the PBT group in any
      of the parameters examined. CONCLUSION: This EGD simulator has limitations to the
      degree of fidelity and can differentiate only novice endoscopists from other
      levels of experience. Finally, skills learned during EGD simulation training do
      not appear to translate well into patient-based endoscopy skills. These findings
      suggest against a key element of validity for the use of this computer simulator
      in novice EGD training.

PMID- 17559387
TI  - Oomycete genomics: new insights and future directions.
AB  - The oomycetes form a distinct phylogenetic lineage of fungus-like eukaryotic
      microorganisms that are relatively closely related to photosynthetic algae such
      as brown algae and diatoms. Plant pathogenic species, notably those of the genus
      Phytophthora, are the best-studied oomycetes. The genomes of four Phytophthora
      and one downy mildew species were recently sequenced resulting in novel insights
      on the evolution and pathogenesis of oomycetes. This review highlights key
      findings that emerged from these studies and discusses the future challenges for
      oomycete research.

PMID- 17559388
TI  - Prevalence, genetic conservation and transmissibility of the Chlamydia pneumoniae
      bacteriophage (phiCpn1).
AB  - The Chlamydia pneumoniae bacteriophage was first identified in isolate AR-39. Its
      relevance for chlamydial biology and pathogenicity remains unknown. In this
      study, a collection of 36 C. pneumoniae isolates was screened and the phage was
      detected in eight. As the positive isolates differed by several polymorphisms,
      they presumably belonged to different genetic lineages. It was investigated
      whether different genotypes of the phage also existed and whether they could be
      assigned to chlamydial genotypes as evidence of coevolution. Sequencing of >3000
      bp of the 4524 bp phage genome revealed complete identity to the published
      sequences. Thus, it was hypothesized that the genetic conservation was related to
      easy transmissibility of the phage between C. pneumoniae isolates. Cocultivation
      of phage positive and negative isolates followed by cloning and identification of
      different C. pneumoniae genotypes demonstrated for the first time
      transmissibility of the bacteriophage from one isolate to the other. These
      observations indicate that the phage is capable of infecting C. pneumoniae
      isolates of different genetic backgrounds and suggest that all C. pneumoniae
      strains might be susceptible. The successful in vitro infection of C. pneumoniae
      with the phage provides the basis for studying its pathogenetic relevance in
      isolates of identical genetic background and provides a potential tool for
      genetic manipulation of C. pneumoniae.

PMID- 17559389
TI  - Development of a molecular method to detect and quantify Aphanomyces euteiches in
      soil.
AB  - A real-time PCR assay using 136F/211R primers and 161T TaqMan probe for the
      detection and quantification of Aphanomyces euteiches in soil is presented. The
      specificity of primers was tested on 105 different A. euteiches isolates, mainly
      from France. A calibration curve was established with a plasmid pHS1 resulting
      from the target region cloned into the pCR4 Topo vector (Invitrogen). The target
      copy number was evaluated and was constant whatever the isolate. A DNA-based
      method was able to discriminate between different artificial infestation levels
      in soil with small SDs thus validating the relevance of the extraction and
      amplification method in soil samples. Furthermore, a good correlation was
      observed between inoculum quantity in soil estimated by qPCR and root rot
      severity in plant evaluated by bioassays. These steps are essential when
      considering the feasibility of using a DNA-based method as a fast and accurate
      way to evaluate inoculum quantity in soil.

PMID- 17559390
TI  - A novel strategy for enzymatic synthesis of 4-hydroxyisoleucine: identification
      of an enzyme possessing HMKP (4-hydroxy-3-methyl-2-keto-pentanoate) aldolase
      activity.
AB  - A two-step enzymatic synthesis process of 4-hydroxyisoleucine is suggested. In
      the first step, the aldol condensation of acetaldehyde and alpha-ketobutyrate
      catalyzed by specific aldolase results in the formation of 4-hydroxy-3-methyl-2
      keto-pentanoate (HMKP). In the second step, amination of HMKP by the branched
      chain amino acid aminotransferase leads to synthesis of 4-hydroxyisoleucine. An
      enzyme possessing HMKP aldolase activity (asHPAL) was purified 2500-fold from a
      crude extract of Arthrobacter simplex strain AKU 626. Sequencing of the asHPAL
      structural gene showed that the purified enzyme belongs to the HpcH/HpaI aldolase
      family. The 4-hydroxyisoleucine was synthesized in vitro from acetaldehyde, alpha
      ketobutyrate and l-glutamate using a coupled aldolase/branched-chain amino acid
      aminotransferase bienzymatic reaction.

PMID- 17559391
TI  - Transcriptional organization of the Porphyromonas gingivalis fimA locus.
AB  - Two different transcriptional start sites, as well as promoter regions and
      translational starts, have been proposed for the fimA gene encoding a long
      fimbriae subunit protein of Porphyromonas gingivalis. In this study, the fimA
      promoter regions and organization of the fimA operon were characterized. The two
      putative promoter regions for fimA were fused with a lacZ reporter gene, cloned
      into the shuttle plasmid vector pT-COW, and the recombinant plasmids were
      introduced to P. gingivalis 33277. Reverse transcriptase-polymerase chain
      reaction demonstrated mRNA production from the promoter proximal to the
      translational start. LacZ activities of P. gingivalis containing the recombinant
      plasmids showed that maximal expression of fimA was promoted by the proximal
      promoter in combination with distal regulatory sequences. A polycistronic message
      spanning PG2130, PG2131 and fimA (PG2132) was observed, thus fimA transcripts may
      also be generated by processing of the polycistronic message.

PMID- 17559392
TI  - Fim operon variation in the emergence of Enterohemorrhagic Escherichia coli: an
      evolutionary and functional analysis.
AB  - Fim operons were examined to illuminate the emergence of Escherichia coli O157:H7
      from the less-virulent E. coli O55:H7. A fim invertible element deletion occurred
      only after O157:H7 descended from O55:H7, and after sorbitol nonfermenting O157
      diverged. Type 1 pili nonexpression correlates with this deletion in all
      enterohemorrhagic E. coli (EHEC) tested. An N135K FimH mutation in the two most
      evolved O157:H7 clusters is not found in other EHEC. These data refine the
      evolutionary history of an emerging pathogen.

PMID- 17559393
TI  - Identification and properties of an inducible phenylacyl-CoA dehydrogenase in
      Pseudomonas putida KT2440.
AB  - A novel acyl-CoA dehydrogenase that initiates beta-oxidation of the side chains
      of phenylacyl-CoA compounds by Pseudomonas putida was induced by growth with
      phenylhexanoate as carbon source. It was identified as the product of gene
      PP_0368, which was cloned and overexpressed in Escherichia coli. This phenylacyl
      CoA dehydrogenase was found to be dimeric with a subunit molecular mass of 66
      kDa, to contain FAD and to be active with phenylacyl-CoA substrates having side
      chains from four to at least 11 carbon atoms. The same enzyme was induced by the
      aliphatic alkanoate octanoate. The optimal aliphatic substrates for the enzyme
      were palmitoyl-CoA and stearoyl-CoA, a property shared with mammalian very-long
      chain acyl-CoA dehydrogenases. The FAD in the enzyme was reduced by aromatic and
      aliphatic substrates, with changes to the oxidation-reduction potential. Chemical
      reduction by dithionite ion and oxidation by ferricyanide ion showed that the
      enzyme can accept four electrons: two to reduce the flavin and two to slowly
      reduce an unknown acceptor, which in its reduced form interacts with the oxidized
      flavin in a charge-transfer complex. The experiments identify for the first time
      an acyl-CoA dehydrogenase that oxidizes the activated forms of aromatic acids
      similar to those used to first demonstrate the biological beta-oxidation of fatty
      acids.

PMID- 17559394
TI  - Maturation of fimbria precursor protein by exogenous gingipains in Porphyromonas
      gingivalis gingipain-null mutant.
AB  - Porphyromonas gingivalis expresses several virulence factors such as fimbriae and
      proteases, termed gingipains, which are enzymes that process precursor fimbriae
      proteins. Thus, gingipain-null mutants lack mature fimbriae. Membrane vesicle
      depleted supernatants (VDS) containing soluble gingipains were prepared as an
      exogenous gingipain fraction. Precursor proteins were treated with VDS and a
      fimbriated gingipain-null mutant was successfully generated. Experiments showed
      that the wild strain adhered to and invaded epithelial cells at a greater level
      than the fimbriated gingipain-null mutant, while adhesion/invasion was prevented
      in the presence of fetal calf serum, which inhibits gingipain activity. The
      findings of this study suggest that gingipains expose cellular cryptic ligands in
      a proteolytic manner and promote fimbriae binding to epithelial cells.

PMID- 17559395
TI  - A molecular Swiss army knife: OmpA structure, function and expression.
AB  - The OmpA outer membrane protein of Escherichia coli and other enterobacteria is a
      multifaceted protein. This protein is expressed to very high levels and ompA is
      tightly regulated at the posttranscriptional level. It can function as an adhesin
      and invasin, participate in biofilm formation, act as both an immune target and
      evasin, and serves as a receptor for several bacteriophages. Many of these
      properties are due to four short protein loops that emanate from the protein to
      the outside of the cell. Herein it is described how the structure of this protein
      relates to its many functions.

PMID- 17559396
TI  - A fully defined, clear and protein-free liquid medium permitting dense growth of
      Neisseria gonorrhoeae from very low inocula.
AB  - Neisseria gonorrhoeae is difficult to cultivate in liquid medium. Currently there
      are no liquid media, defined or undefined, that reliably permit growth of this
      bacterium from low inocula. Standard clinical laboratory broths may allow
      multiplication of some strains of gonococci from large inocula, but such media
      incorporate infusates, extracts or digests and are therefore undefined. In this
      study, 20 gonococci of ten auxotypes were tested in various experimental media in
      the development of an easily prepared chemically defined, clear and protein-free
      liquid medium. The final medium - GW medium - allowed the growth of three
      clinical isolates of gonococci from inocula of <10(3) CFU mL(-1) to >10(8) CFU
      mL(-1) by 24 h. None of four commercially-available broths (nutrient broth, brain
      heart infusion, tryptone soya broth, and Mueller-Hinton broth) tested in parallel
      reliably supported growth of these isolates to the same extent. GW medium should
      be useful for studies of the growth of gonococci under different conditions and,
      as the medium is clear and colorless, this can be monitored turbidometrically. GW
      medium may be suitable as a basal medium for biochemical identification tests,
      antimicrobial susceptibility determinations and antimicrobial synergy studies.

PMID- 17559397
TI  - Comparison of growth-phase-dependent cytosolic proteomes of two Lactobacillus
      plantarum strains used in food and feed fermentations.
AB  - Lactobacillus plantarum is a facultative heterofermentative lactic acid bacterium
      highly adapted to a wide variety of environments and widely used in food and feed
      fermentations. Proteomes of two strains of L. plantarum, one isolated from
      spontaneously fermented cereal-based feed (strain REB1), and the other from white
      cabbage (strain MLBPL1), were studied to elucidate the strain-specific variation
      and the physiological changes occurring between the growth (lag, early
      exponential, late-exponential and early-stationary) phases of this bacterium when
      cultivated in a standard rich medium. A total of 231 protein spots were
      identified by LC-MS/MS. These proteins showed that strain MLBPL1 had more
      proteins with growth phase-dependent expression than REB1, which possesses a more
      constant expression profile. The proteins with growth phase-dependent expression
      in REB1 and MLBPL1 were mainly associated with energy metabolism (glycolysis,
      phosphoketolase pathway and ribose metabolism), all having preferential
      expression in the early-exponential phase, confirming the use of different
      carbohydrates simultaneously. Indication of energy production was also seen in
      lag and early-stationary phases.

PMID- 17559398
TI  - Characterization of two components of the 2-naphthoate monooxygenase system from
      Burkholderia sp. strain JT1500.
AB  - 2-Naphthoate monooxygenase, a two-protein system, encoded by the nmoA and nmoB
      genes, was heterologously overexpressed in Escherichia coli. The proteins used
      for functional characterization were purified to over 90% homogeneity by affinity
      chromatography. The oxidative component EnmoA (47.9 kDa) lacked substrate
      catalysis capability on its own, and the reductive component EnmoB (33.4 kDa) and
      its truncated derivate EnmoB(T) (25 kDa) possessed nearly identical independent
      flavin reductase activities, c. 130 micromol min(-1) mg(-1) of protein. The
      inframe fusioned protein EnmoB(T)A (65.2 kDa), containing NmoB(T) and NmoA
      peptides showed a stable 2-naphthoate monooxygenase activity of 1.2 micromol min(
      1) mg(-1) of protein. This is the first report on the purification of a fused
      form of a two-component flavoprotein monooxygenase. In the specificity
      experiment, FAD and NADH were shown to be preferred cosubstrates for EnmoB and
      EnmoB(T). All these data suggest that NmoB(T)A is a two-component flavoprotein
      monooxygenase, consisting of an oxygenase and a reductase component. NmoA is a
      member of the class D flavoprotein monooxygenase, and NmoB is an independent
      NADH:Flavin oxidoreductase.

PMID- 17559399
TI  - Examination of Pseudomonas aeruginosa lasI regulation and 3-oxo-C12-homoserine
      lactone production using a heterologous Escherichia coli system.
AB  - In Pseudomonas aeruginosa, the signaling molecule 3-oxo-C12-homoserine lactone
      (3OC12HSL) is synthesized by LasI, and lasI transcription is positively regulated
      by LasR. A heterologous model has been generated for the study of the
      LasRI/3OC12HSL regulatory network in Escherichia coli. Escherichia coli pAHL-BAC
      cultures produced LasI-synthesized acylhomoserine lactones (AHLs) at levels and
      with kinetics similar to what is observed in cultures of P. aeruginosa strain
      PAO1. Analysis of the lasI transcript also showed similar induction profiles in
      both the E. coli pAHL-BAC strain and P. aeruginosa. Transposon mutagenesis of
      pAHL-BAC confirmed that transcriptional regulation by LasR is necessary for
      3OC12HSL production, and showed that artificially increasing lasI transcript
      levels leads to higher levels of 3OC12HSL. Previous studies have shown that P.
      aeruginosa 3OC12HSL inhibits hypha formation, but not growth, in Candida
      albicans, and the E. coli pAHL-BAC similarly inhibited filamentation when grown
      in coculture with the fungus. It is proposed that this system will be useful for
      the study of factors that impact lasI regulation and 3OC12HSL production, and for
      the examination of the role of LasI-produced AHLs in bacterial interactions with
      other organisms.

PMID- 17559400
TI  - Sesquiterpene farnesol as a competitive inhibitor of lipase activity of
      Staphylococcus aureus.
AB  - Staphylococcus aureus lipase (SAL) is known to possess broad substrate
      specificity for triacylglycerides. We found that a sub-minimum inhibitory
      concentration of farnesol (1000 mg L(-1)) inhibits this lipase activity on a
      Mueller-Hinton agar containing 1% Tween substrates. A quantitative lipase assay
      using p-nitrophenyl palmitate (pNPP) revealed that the inhibitory action of
      farnesol appears to be the result of the inhibition of lipase activity rather
      than of its secretion into the culture medium. The inhibition was observed in all
      the tested 8 methicillin-susceptible S. aureus and 31 methicillin-resistant S.
      aureus clinical isolates. Using homogeneous lipase purified by hydrophobic
      interaction chromatography, it was revealed that farnesol could competitively
      inhibit the lipase activity against the substrate pNPP.

PMID- 17559401
TI  - Unusual accumulation of polymorphic microsatellite loci in a specific region of
      the mitochondrial genome of two mushroom-forming Agrocybe species.
AB  - The cob/tRNA(Tyr) mitochondrial regions of Agrocybe aegerita and of the related
      species Agrocybe chaxingu display an unusual clustering of four microsatellite
      loci constituted by motifs of one to six nucleotides whose number of repeats
      varied from three to 18. In A. chaxingu, these microsatellite loci are followed
      by a small region bearing one additional microsatelite and one minisatellite
      locus constituted by an octanucleotide motif repeated 13-18 times. In A.
      aegerita, this latter region is deleted. This is the first evidence of such an
      accumulation of microsatellites in mitochondrial genomes. The analyses of the
      microsatellite loci in 11 A. aegerita and in four A. chaxingu wild strains have
      shown extensive intraspecific and interspecific variations in the number of
      tandem repeats (VNTRs), suggesting that these loci could represent powerful
      molecular markers for strain fingerprinting. Up to 23 different alleles were
      present in the 15 Agrocybe studied strains, allowing the definition of 12
      different haplotypes.

PMID- 17559402
TI  - Molecular features of Mycobacterium avium human isolates carrying a single copy
      of IS1245 and IS1311 per genome.
AB  - Human clinical isolates of the Mycobacterium avium complex, from hospitals in
      Bogota, were studied using a wide range of molecular tests including PCR
      restriction-enzyme analysis (PRA) of the hsp65 gene. Up to 21 of the isolates
      were identified as M. avium PRA variant III (Mav III), a variant obtained only
      from isolates on the American continent. In contrast to previous reports,
      restriction fragment length polymorphism analysis using IS1245 and IS1311 showed
      a single copy for each insertion sequence (IS) in the majority (19/21) of the
      Colombian Mav III isolates under study. In order to analyse whether the ISs were
      inserted in a relevant genomic region, experimental conditions were established
      to determine the insertion loci of each single copy of both ISs in the genome.
      Analysis of genomic insertion loci indicated that both IS1245 and IS1311 were
      present in areas containing putatively truncated integrases and/or transposases,
      which may have an influence on the mobility of the inserted IS. In addition, a
      conserved genomic region was identified for the insertion of IS1311; this region
      could be part of the IS1311 itself.

PMID- 17559403
TI  - Biochemical characterization of enoyl reductase involved in Type II fatty acid
      synthesis in the intestinal coccidium Eimeria tenella (Phylum Apicomplexa).
AB  - An enoyl reductase (EtENR) closely related to those of green algae and involved
      in Type II fatty acid synthesis was characterized and localized to the apicoplast
      in the coccidium Eimeria tenella. Biochemical analysis using native EtENR protein
      extracted from parasites confirmed its function as an enoyl reductase using NADH
      as a cofactor. However, the recombinant form (rEtENR) expressed in bacteria was
      only able to oxidize NADH, but unable to transfer the electron to enoyl-CoA,
      possibly due to the inappropriate folding of rEtENR expressed in bacteria. The
      functions of both native and recombinant EtENR could be inhibited by triclosan
      (IC(50)=1.45 microM), suggesting that this enzyme may be explored as a drug
      target against coccidiosis.

PMID- 17559404
TI  - Characterization of S-adenosylhomocysteine hydrolase from Cryptosporidium parvum.
AB  - The S-adenosylhomocysteine hydrolase from the apicomplexan Cryptosporidium parvum
      (CpSAHH) has been characterized. CpSAHH is a single-copy, intronless gene of 1479
      bp encoding a protein of 493 amino acids with a molecular mass of 55.6 kDa.
      Reverse transcriptase-polymerase chain reaction analysis confirmed that CpSAHH is
      expressed both in intracellular stages (in C. parvum-infected HCT-8 cells 24 h
      after infection) and in sporozoites. CpSAHH was expressed in Escherichia coli TB1
      cells as a fusion with maltose-binding protein. The recombinant fusion was
      cleaved by Factor Xa and the enzymatic activity of both the fusion protein and
      the purified separated CpSAHH was measured. The enzymatic activity of CpSAHH was
      inhibited by d-eritadenine, S-DHPA and Ara-A.

PMID- 17559405
TI  - Characterization of citrate utilization in Corynebacterium glutamicum by
      transcriptome and proteome analysis.
AB  - Corynebacterium glutamicum grows aerobically on a variety of carbohydrates and
      organic acids as single or combined sources of carbon and energy. To characterize
      the citrate utilization in C. glutamicum on a genomewide scale, a comparative
      analysis was carried out by combining transcriptome and proteome analysis. In
      cells grown on citrate, transcriptome analysis revealed highest expression
      changes for two different citrate-uptake systems encoded by citM and tctCBA,
      whereas genes encoding uptake systems for the glucose- (ptsG), sucrose- (ptsS)
      and fructose- (ptsF) specific PTS components and permeases for gluconate (gntP)
      and glutamate (gluC) displayed decreased mRNA levels in citrate-grown cells. This
      pattern was also observed when cells grown in Luria-Bertani (LB) medium plus
      citrate were compared with cells grown in LB medium, indicating some kind of
      catabolite repression. Genes encoding enzymes of the tricarboxylic acid cycle
      (aconitase, succinyl-CoA synthetase, succinate dehydrogenase and fumarase), malic
      enzyme, PEP carboxykinase, gluconeogenic glyceraldehyde-3-phosphate dehydrogenase
      and ATP synthase displayed increased expression in cells grown on citrate.
      Accordingly, proteome analysis revealed elevated protein levels of these enzymes
      and showed a good correlation with the mRNA levels. In conclusion, this study
      revealed the citrate stimulon in C. glutamicum and the regulated central
      metabolic genes when grown on citrate.

PMID- 17559406
TI  - Evidence for convergent evolution of CTX-M-14 ESBL in Escherichia coli and its
      prevalence.
AB  - A total of 2440 Escherichia coli strains isolated in 2003 at the Hospital de la
      Santa Creu i Sant Pau were evaluated for the presence of extended-spectrum beta
      lactamases. Two different nucleotide sequences that encode the same beta
      lactamase, CTX-M-14, were detected when the bla(CTX-M-14)-genes of 35 E. coli
      isolates were analysed. Thirty-two of the 35 had the previously described
      sequence of the bla(CTX-M-14) (AF252622), named bla(CTX-M-14a), and the remaining
      three isolates showed a nucleotide sequence identical to that of the bla(CTX-M-9)
      gene except for one nucleotide, named bla(CTX-M-14b). Characterisation of the
      regions surrounding the bla(CTX-M-14a) showed the ISEcp1 and the IS903 upstream
      and downstream, respectively, of the bla gene, whereas the regions surrounding
      the bla(CTX-M-14b) contained the genetic environment described for the bla(CTX-M
      9) gene, the In60. Characterisation by hybridisation showed that the bla(CTX-M
      14a) was present in IncK plasmids, whereas the bla(CTX-M-14b) was found in the
      HI2 Inc group. The CTX-M-14 ESBL in E. coli isolates is the result of the
      convergence of two different genes.

PMID- 17559407
TI  - Power law rank-abundance models for marine phage communities.
AB  - Metagenomic analyses suggest that the rank-abundance curve for marine phage
      communities follows a power law distribution. A new type of power law dependence
      based on a simple model in which a modified version of Lotka-Volterra predator
      prey dynamics is sampled uniformly in time is presented. Biologically, the model
      embodies a kill the winner hypothesis and a neutral evolution hypothesis. The
      model can match observed power law distributions and uses very few parameters
      that are readily identifiable and characterize phage ecosystems. The model makes
      new untested predictions: (1) it is unlikely that the most abundant phage
      genotype will be the same at different time points and (2) the long-term decay of
      isolated phage populations follows a power law.

PMID- 17559408
TI  - Characterization of DhKHA1, a gene coding for a putative Na(+) transporter from
      Debaryomyces hansenii.
AB  - The KHA1 gene from Debaryomyces hansenii has been identified and characterized by
      heterologous expression in Saccharomyces cerevisiae. The gene is orthologous to
      ScKHA1, previously reported in S. cerevisiae, and on the basis of the deduced
      amino acid sequence, DhKha1p can be classified as an Na(+)/H(+) transporter.
      Reverse transcriptase (RT)-PCR experiments indicated that the expression level of
      DhKHA1 was not dependent on high pH or on the presence of a high salt level in
      the growth medium. Overexpression of DhKHA1 in a salt-sensitive S. cerevisiae
      mutant (ena1-4 nha1 kha1) rendered cells specifically more tolerant to Na(+). In
      addition, internal K(+) and Na(+) measurements and experiments performed with
      green fluorescence protein (GFP)-tagged DhKha1p indicated the intracellular
      localization of this protein when expressed in S. cerevisiae.

PMID- 17559409
TI  - Further study of the Hansenula polymorpha MAL locus: characterization of the
      alpha-glucoside permease encoded by the HpMAL2 gene.
AB  - The HpMAL2 gene of the MAL gene cluster of Hansenula polymorpha codes for a
      permease similar to yeast maltose and alpha-glucoside transporters. Genomic
      disruption of HpMAL2 resulted in an inability of cells to grow on maltose,
      sucrose, trehalose, maltotriose and turanose, as well as a lack of p-nitrophenyl
      alpha-D-glucopyranoside (PNPG) transport. PNPG uptake was competitively inhibited
      by all these substrates, with Ki values between 0.23 and 1.47 mM. Transport by
      HpMal2p was sensitive to pH and a protonophore carbonyl cyanide-m
      chlorophenylhydrazone (CCCP), revealing its energization by the proton gradient
      over the cell membrane. Although HpMAL2 was responsible for trehalose uptake, its
      expression was not induced during trehalose growth. A maltase disruption mutant
      did not grow on maltotriose and turanose, whereas it showed normal growth on
      trehalose, demonstrating the dispensability of maltase for intracellular
      hydrolysis of trehalose. In a Genolevures clone pBB0AA011B12, the promoter region
      and the N-terminal fragment of the putative transactivator of MAL genes is
      located adjacent to HpMAL2. A reporter gene assay showed that expression from
      that promoter was induced by maltose and sucrose, repressed by glucose, and
      derepressed during glycerol and trehalose growth. Therefore, we presume that the
      gene encodes a functional regulator.

PMID- 17559411
TI  - Alcohol-conferred hemolysis in yeast is a consequence of increased respiratory
      burden.
AB  - We have previously reported that growth on alcohol vapors confers hemolytic
      properties on certain yeast species and strains ('microbial alcohol conferred
      hemolysis'; MACH). Here, a Saccharomyces cerevisiae deletion library consisting
      of c. 4800 clones was screened for MACH mutants in the presence of n-butanol
      vapors; 136 mutants were MACH-negative, and 325 exhibited reduced hemolysis
      and/or growth. Of the MACH-negative mutants, 35.3% were affected in mitochondrial
      related genes. The data suggest that intact mitochondrial and respiratory chain
      functions are critical for the observed MACH phenomenon. We propose that the
      uncontrolled cellular uptake of alcohol results in yeast 'hyper-respiration',
      leading to elaboration of hemolytic molecules such as hydrogen peroxide and
      hemolysis-causing lipids. To support this premise, we showed that: (1) exogenous
      catalase and glutathione reduce alcohol-conferred hemolysis in S. cerevisiae
      BY4741 and Candida tropicalis 59445; (2) C. tropicalis produces hydrogen peroxide
      following growth on ethanol and n-butanol, as shown using xylenol orange; and (3)
      a lysophospholipid-containing lipid extract from alcohol-grown C. tropicalis
      specifically causes hemolysis.

PMID- 17559410
TI  - Peptidase profiles from non-albicans Candida spp. isolated from the blood of a
      patient with chronic myeloid leukemia and another with sickle cell disease.
AB  - Candida lipolytica and Candida rugosa were isolated from blood samples from a
      patient with chronic myeloid leukemia (31 years old) and a patient with sickle
      cell disease (1-year-old), respectively. Isolates were grown for 48 h at 37
      degrees C in either Sabouraud or tryptone soy broth (TSB). Peptidases were tested
      for using substrate sodium dodecyl sulfate-polyacrylamide gels with gelatin,
      casein, bovine serum albumin (BSA) or hemoglobin. Enzymography analyses were made
      on the following substrates: human albumin, IgG and human fibrinogen, which had
      been incubated with the concentrated supernatants. For C. lipolytica, a
      approximately 60-kDa gelatin-degrading serine proteolytic activity was found in
      the TSB supernantant as well as a metallopeptidase activity capable of
      hydrolysing human albumin, IgG and human fibrinogen. With C. rugosa, albumin, IgG
      and human fibrinogen substrates were degraded by an aspartyl-like peptidase
      activity. Supernatants from C. rugosa also showed three serine proteolytic
      activities towards gelatin (approximately 50 kDa, TSB), casein ( approximately 94
      kDa, TSB) and BSA ( approximately 120-kDa, Sabouraud), in addition to a
      metallopeptidase capable of degrading casein ( approximately 110 kDa, Sabouraud).
      Little is known about peptidases of C. rugosa and C. lipolytica and this
      preliminary data may prove useful for future work on host-parasite relationship
      and antifungal agents.

PMID- 17559412
TI  - Promoter heterozygosity at the Candida albicans CHS7 gene is translated into
      differential expression between alleles.
AB  - A characteristic genetic trait in Candida albicans is diploidism, which is
      accompanied by a high degree of natural heterozygosity. Here, we describe natural
      heterozygosity in the promoter of the CaCHS7 gene in the SC5314 strain,
      associated with a GC-rich sequence of 28 nucleotides. Both alleles are expressed
      in the wild type and contribute to the total levels of the CaCHS7 mRNA. However,
      the presence of this region in the promoter (L allele) significantly reduced the
      transcription of the gene as compared with its absence (S allele). Heterozygous
      strains containing either allele showed distinct phenotypic characteristics. The
      HeteroL strain showed reduced levels of chitin, a partial resistance to
      calcofluor, and a moderate degree of morphogenetic alterations in hypha-inducing
      media. The HeteroS strain was very similar to the wild type, showing only a
      modest decrease in chitin that did not appear to confer distinct phenotypic
      characteristics. This is therefore a new report about allelic heterogeneity in C.
      albicans, directly translated into differential regulation of both alleles,
      leading to phenotypic consequences. The allelic heterogeneity reported appears to
      be strain-specific. However, sequence comparison between strains indicated that
      this region is prone to genetic divergence, which is probably responsible for the
      reported allelic heterozygosity of CaCHS7.

PMID- 17559413
TI  - Cloning and characterization of the NADPH cytochrome P450 reductase gene (CPR)
      from Candida bombicola.
AB  - Candida bombicola is a yeast with at least two appealing features. The species
      can grow on alkanes when provided as the sole carbon source, and it produces
      glycolipids, which have several industrial, cosmetic and pharmaceutical
      applications. Both metabolic processes require in their pathway the activity of
      cytochrome P450 monooxygenase. This enzyme needs and gets reducing equivalents
      from NADPH cytochrome P450 reductase (CPR). The CPR gene of Candida bombicola was
      isolated using degenerate PCR and genomic walking. The gene encodes an enzyme of
      687 amino acids, which shows homology with known CPRs of other species. The
      functionality of the gene was proven by heterologous expression in Escherichia
      coli. The recombinant protein exhibited NADPH-dependent cytochrome c reducing
      activity. Cloning and characterization of this enzyme is an important step in the
      study of the cytochrome P450 monooxygenase system of Candida bombicola. The
      GenBank accession number of the sequence described in this article is EF050789.

PMID- 17559414
TI  - Functional characterization of the phosphorelay protein Mpr1p from
      Schizosaccharomyces pombe.
AB  - Histidine-containing phosphotransfer (HPt) proteins play an essential role in
      multistep histidine-aspartate phosphorelay signal transduction systems in
      prokaryotes and eukaryotes. The putative HPt protein in Schizosaccharomyces
      pombe, Mpr1p (also known as Spy1p), is a 295 amino acid protein that appears to
      be composed of more than one functional domain. The amino acid sequence of the N
      terminal region of Mpr1p lacks homology to other known proteins, whereas the C
      terminal domain is predicted to have structural similarity to the Ypd1p HPt
      protein from Saccharomyces cerevisiae. This study provides both in vitro and in
      vivo evidence that the C-terminal domain of Mpr1p indeed functions as an HPt
      protein in shuttling phosphoryl groups from one response regulator domain to
      another. Furthermore, we find that various deletions of the N-terminal region
      diminish both the phosphotransfer activity of Mpr1p and its affinity for response
      regulator domains, suggesting a possible role for the N-terminal domain in HPt
      response regulator domain interactions.

PMID- 17559415
TI  - Elevated levels of human endogenous retrovirus-W transcripts in blood cells from
      patients with first episode schizophrenia.
AB  - We previously reported on the differential presence of transcripts related to the
      human endogenous retrovirus (HERV)-W family in cerebrospinal fluid and plasma
      from patients with first-episode schizophrenia compared with control individuals.
      Whether this is a consequence of qualitative or quantitative differences in
      transcription of genomic regions harboring HERV-W elements is not known. The
      purpose of the present study was therefore to characterize the transcribed HERV-W
      elements in mononuclear cells obtained from 30 patients first hospitalized for
      schizophrenia-related psychosis and from 26 healthy control individuals. We
      observed elevated total levels of HERV-W gag (2.1-fold, P < 0.01) but not env
      transcripts in the cells of patients compared with controls. By using the melting
      temperatures of the amplicons as a proxy marker for sequence identity, no
      absolute qualitative differences was detected between the two groups. Mapping of
      the detected transcripts identified several intronic and intergenic HERV-W
      elements transcribed in the cells, including elements previously considered
      transcriptionally silent. Element-specific assays revealed elevated levels of
      intronic transcripts containing HERV-W gag sequence from the putative gene PTD015
      on chromosome 11q13.5 (1.6-fold, P < 0.05) in the patients compared with the
      controls. Thus, studies aiming to further understanding of complex human disease
      such as schizophrenia may need to be extended beyond the strictly protein-coding
      fraction of the transcriptome.

PMID- 17559416
TI  - A polygenic heterogeneity model for common epilepsies with complex genetics.
AB  - Approximately 40% of epilepsy has a complex genetic basis with an unknown number
      of susceptibility genes. The effect of each susceptibility gene acting alone is
      insufficient to account for seizure phenotypes, but certain numbers or
      combinations of variations in susceptibility genes are predicted to raise the
      level of neuronal hyperexcitability above a seizure threshold for a given
      individual in a given environment. Identities of susceptibility genes are
      beginning to be determined, initially by translation of knowledge gained from
      gene discovery in the monogenic epilepsies. This entree into idiopathic
      epilepsies with complex genetics has led to the experimental validation of
      susceptibility variants in the first few susceptibility genes. The genetic
      architecture so far emerging from these results is consistent with what we have
      designated as a polygenic heterogeneity model for the epilepsies with complex
      genetics.

PMID- 17559417
TI  - Deletion of the 5-HT(3A)-receptor subunit blunts the induction of cocaine
      sensitization.
AB  - Serotonin (5-HT) receptors are classified into seven groups (5-HT(1-7)),
      comprising at least 14 structurally and pharmacologically distinct receptor
      subtypes. Pharmacological antagonism of ionotropic 5-HT(3) receptors has been
      shown to modulate both behavioral and neurochemical aspects of the induction of
      sensitization to cocaine. It is not known, however, if specific molecular
      subunits of the 5-HT(3) receptor influence the development of cocaine
      sensitization. To address this question, we studied the effects of acute and
      chronic intermittent cocaine administration in mice with a targeted deletion of
      the gene for the 5-HT(3A)-receptor subunit (5-HT(3A)-/-). 5-HT(3A) (-/-) mice
      showed blunted induction of cocaine-induced locomotor sensitization as compared
      with wild-type littermate controls. 5-HT(3A) (-/-) mice did not differ from wild
      type littermate controls on measures of basal motor activity or response to acute
      cocaine treatment. Enhanced locomotor response to saline injection following
      cocaine sensitization was observed equally in 5-HT(3A) (-/-) and wild-type mice
      suggesting similar conditioned effects associated with chronic cocaine treatment.
      These data show a role for the 5-HT(3A)-receptor subunit in the induction of
      behavioral sensitization to cocaine and suggest that the 5-HT(3A) molecular
      subunit modulates neurobehavioral adaptations to cocaine, which may underlie
      aspects of addiction.

PMID- 17559418
TI  - Autism-like behavioral phenotypes in BTBR T+tf/J mice.
AB  - Autism is a behaviorally defined neurodevelopmental disorder of unknown etiology.
      Mouse models with face validity to the core symptoms offer an experimental
      approach to test hypotheses about the causes of autism and translational tools to
      evaluate potential treatments. We discovered that the inbred mouse strain BTBR
      T+tf/J (BTBR) incorporates multiple behavioral phenotypes relevant to all three
      diagnostic symptoms of autism. BTBR displayed selectively reduced social
      approach, low reciprocal social interactions and impaired juvenile play, as
      compared with C57BL/6J (B6) controls. Impaired social transmission of food
      preference in BTBR suggests communication deficits. Repetitive behaviors appeared
      as high levels of self-grooming by juvenile and adult BTBR mice. Comprehensive
      analyses of procedural abilities confirmed that social recognition and olfactory
      abilities were normal in BTBR, with no evidence for high anxiety-like traits or
      motor impairments, supporting an interpretation of highly specific social
      deficits. Database comparisons between BTBR and B6 on 124 putative autism
      candidate genes showed several interesting single nucleotide polymorphisms (SNPs)
      in the BTBR genetic background, including a nonsynonymous coding region
      polymorphism in Kmo. The Kmo gene encodes kynurenine 3-hydroxylase, an enzyme
      regulating metabolism of kynurenic acid, a glutamate antagonist with
      neuroprotective actions. Sequencing confirmed this coding SNP in Kmo, supporting
      further investigation into the contribution of this polymorphism to autism-like
      behavioral phenotypes. Robust and selective social deficits, repetitive self
      grooming, genetic stability and commercial availability of the BTBR inbred strain
      encourage its use as a research tool to search for background genes relevant to
      the etiology of autism, and to explore therapeutics to treat the core symptoms.

PMID- 17559419
TI  - Why do young women smoke? V. Role of direct and interactive effects of nicotinic
      cholinergic receptor gene variation on neurocognitive function.
AB  - Previous work suggests that young women who smoke cigarettes regularly, or did so
      in the past, manifest a neurocognitive profile that is characterized by small but
      significant impairments of response inhibition and attention. The present study
      sought to determine whether variation in nicotinic cholinergic receptor (nAchR)
      genes impacts upon cognitive function in these domains by overall or differential
      effects on the performance of current, former and non-smokers. The study sample
      consisted of 100 female college students, current or past smokers, and 144 who
      had never smoked. All performed a computerized neurocognitive test battery and
      were genotyped for 39 single nucleotide polymorphisms in 11 nAchR genes. The
      results, derived from linear or logistic regression, show significant direct and
      interactive relationships between single nucleotide polymorphisms and haplotypes
      in several nAchR genes and performance on the Matching Familiar Figures Test
      (MFFT) Stroop test, Continuous Performance Task (CPT) and Tower of London (TOL)
      test. Response inhibition (MFFT, Stroop, CPT Loading Phase, TOL) was associated
      with variants in CHRNA2, CHRNA4, CHRNA5, CHRNA7, CHRNA9, CHRNA10, CHRNB2 and
      CHRNB3. Selective attention (Stroop) was associated with CHRNA4, CHRNA5, CHRNA9
      and CHRNB2. Sustained attention (CPT Boring Phase) was associated with CHRNA4,
      CHRNA5, CHRNA7, CHRNA10 and CHRNB3. Up to 37% of the variance among the smokers
      and up to 47% of the variance among the non-smokers on the test measures was
      explained. Differences between smokers and non-smokers in neurocognitive
      function, putatively implicated in susceptibility to nicotine dependence, may be
      modulated by variants in nAchR genes, with potential implications for prevention
      and treatment.

PMID- 17559420
TI  - Decrease in accumulation of ultrasound contrast microbubbles in non-alcoholic
      steatohepatitis.
AB  - AIM: Non-alcoholic steatohepatitis (NASH) is one of the representative liver
      diseases in developed countries. Diagnosis of NASH is dependent on histological
      findings from liver biopsy. METHODS: The usefulness of contrast ultrasound with
      Levovist for diagnosis of NASH is described. 2.5 g of ultrasound contrast agent
      Levovist was injected intravenously. The liver was scanned at 5, 10, 15, 20, 30,
      40 and 50 min and changes in microbubble accumulation were evaluated. The signal
      intensity from regions of interest (ROI) on the contrast images was measured and
      estimated using time intensity curves (TICs). Twenty-one patients with NASH, 33
      with non-alcoholic fatty liver disease (NAFLD) and 10 healthy volunteers (HV)
      were studied. The signal intensity was measured quantitatively at 5 and 20 min
      after injection. RESULTS: There was a statistically significant decrease in NASH,
      when compared with NAFLD and HV groups. These changes in signal intensity were
      not correlated to the degree of fibrosis and steatosis in histological study. The
      sensitivity, specificity and overall accuracy obtained from the receiver
      operating characteristic (ROC) curve were 100% when the cut-off value was set at
      43.6 of signal intensity at 20 min. CONCLUSION: The Levovist contrast study is a
      useful screening examination which picks up NASH among fatty liver patients.

PMID- 17559421
TI  - Importance of inhibitor of DNA binding/differentiation 2 in hepatic stellate cell
      differentiation and proliferation.
AB  - BACKGROUND/AIM: In liver fibrosis, activated hepatic stellate cells (HSC) are
      transformed into myofibroblasts. Helix-loop-helix (HLH) transcriptional factors
      such as MyoD regulate the differentiation of myocytes, and the inhibitor of DNA
      binding/differentiation (Id) family comprises dominant negative HLH
      transcriptional regulators that inhibit differentiation and promote cell
      proliferation. In the present study, we investigated how the Id family proteins
      regulate HSC. METHODS: In primary rat HSC, inhibitor of DNA
      binding/differentiation (Id)2 and alpha-smooth muscle actin (alpha-SMA) mRNA
      expression increased 4 days after isolation. Next we established Id2 expressing
      HSC (HSC-T6-Id2-green fluorescent protein (GFP)) using HSC-T6 cells with
      retrovirus that expressed GFP-tagged Id2. RESULTS: HSC-T6-Id2-GFP increased cell
      proliferation with cyclin D1 expression. In contrast, alpha-SMA expression
      wassuppressed. Real-time reverse transcription-polymerase chain reaction analysis
      showed Id2 induction significantly suppressed alpha-SMA, collagen-1, matrix
      metalloproteinase (MMP)-2, and MMP-9 mRNA (P < 0.05) but had no effect on tissue
      inhibitor of metalloproteinase or transforming growth factor-beta1 levels.
      CONCLUSION: These findings suggest Id2, an HLH transcriptional regulator, plays
      an important regulatory role in the proliferation and differentiation of HSC.

PMID- 17559422
TI  - Clinical features of Japanese type 1 autoimmune hepatitis patients with zone III
      necrosis.
AB  - AIM: In Caucasians in northern Europe and North America, type 1 autoimmune
      hepatitis is characterized by susceptibility to human leukocyte antigens DR3 and
      DR4, and patients with zone III necrosis more frequently have an acute onset of
      the disease and a lower frequency of cirrhosis than those without. In Japanese
      patients, however, type 1 autoimmune hepatitis is primarily associated with DR4,
      and there are almost no DR3-positive patients. Thus, the clinical features of
      Japanese patients with type 1 autoimmune hepatitis and zone III necrosis may be
      different from those reported previously for Caucasians. METHODS: We investigated
      160 consecutive patients with type 1 autoimmune hepatitis (20 males and 140
      females; median age, 55 years; range, 16-79 years). RESULTS: Forty-seven patients
      (29%) had zone III necrosis, and these patients had lower serum levels of albumin
      and higher serum levels of total bilirubin, aspartate aminotransferaseand alanine
      aminotransferase. Histologically, zone III necrosis was found more frequently in
      patients with acute hepatitis than in those with chronic hepatitis. However,
      there was no difference in the frequency of cirrhosis between patients with and
      without zone III necrosis. In addition, normalization of serum alanine
      aminotransferase levels within six months after the introduction of
      corticosteroid treatment was slightly more frequent in patients with zone III
      necrosis (95% vs. 88%). CONCLUSION: In Japanese patients, zone III necrosis may
      reflect not only acute autoimmune hepatitis, but also acute exacerbation of pre
      existing chronic disease. Furthermore, patients with zone III necrosis may
      respond better to corticosteroid treatment than those without.

PMID- 17559423
TI  - Amino acid substitutions in the S region of hepatitis B virus in sera from
      patients with acute hepatitis.
AB  - BACKGROUND: An increase in the number of acute hepatitis patients with hepatitis
      B virus (HBV) of non-indigenous genotypes may reduce the efficacy of vaccination
      against HBV. METHODS: We have determined the amino acid (aa) sequences in the
      major hydrophilic region (MHR) in the S region of HBV in patients with acute
      hepatitis B and compared those with the ones from HBV strains used for the
      production of HBV vaccines commercially available in Japan. RESULTS: Of 48
      patients studied, 11 were infected with genotype A, 11 with genotype B and 26
      with genotype C HBV. The aa sequences of the nine genotype A isolates were the
      same as the aa sequence of J02205 which is used for the production of one of the
      commercially available recombinant vaccines. The aa sequences of the 11 genotype
      B isolates differed from the aa sequence of J02205 in two or three amino acids.
      Of the26 genotype C isolates, 22 had the same aa sequence as X01587 which is used
      for the production of another recombinant vaccine. The remaining genotype C
      isolates had aa substitutions at aa131, which have a potential to alter the
      hydropathy and the three-dimensional structure of the MHR. The differences among
      the three current HBV vaccines in aa sequences in the MHR theoretically alter the
      hydropathy and three-dimensional structure. CONCLUSION: Our results suggest that
      the transmission of HBV isolates with different genotypes or with aa
      substitutions in the MHR might reduce the efficacy of currently available HBV
      vaccines in the protection of HBV infections.

PMID- 17559424
TI  - Combination antibody-based cancer immunotherapy.
AB  - It is now commonly recognized that tumor-targeting monoclonal antibodies (mAb)
      demonstrate significant therapeutic effects in cancer patients. Multiple effector
      mechanisms are involved in the primary response; however, the induction of tumor
      specific immunity has sometimes been a desired outcome and in some cases has
      contributed to the success of mAb-based therapy. Initiating the antitumor immune
      response by creating a tumor antigen supply from dying (apoptotic) tumor cells is
      a goal of tumor-targeting mAb therapy, and ideally a sufficiently immunogenic
      tumor cell death might provide a platform on which combination immunotherapies
      can be based. In this review, the authors discuss the possible utility and
      pitfalls of using such a therapy, which combines tumor cell death with immune
      activation therapy. The ideas are largely based on the observation that three-mAb
      (anti-DR5 mAb, anti-CD40 mAb, and anti-CD137 mAb [trimAb]) therapy has been shown
      to be very effective in a number of mouse experimental tumor models. The authors
      believe that this rational activation and inhibition of key points in the immune
      response can be an effective strategy to apply in human cancer patients.

PMID- 17559425
TI  - Identification of mitochondrial FoF1-ATP synthase involved in liver metastasis of
      colorectal cancer.
AB  - Liver metastasis is a major cause of poor survival of colorectal cancer patients.
      In order to identify the proteins associated with liver metastasis in colorectal
      cancer, we carried out two-dimensional gel electrophoresis-based comparative
      proteomic analysis of normal colon mucosa, primary colon cancer tissue and
      corresponding metastatic tumor tissue in liver. The proteins identified were
      further validated by immunohistochemical analysis of 67 quadruplet samples of
      normal colon primary colorectal cancer and normal liver-synchronous liver
      metastasis, and 251 colorectal cancers as well as in vitro invasion assay of the
      human colon cancer cell line, SNU-81. From proteomic assessment, the
      mitochondrial FoF1-ATP synthase (ATP synthase) alpha-subunit was identified as a
      protein that is upregulated in liver metastasis compared with the primary tumor.
      Immunohistochemical analyses confirmed a significant increase in the expression
      of ATP synthase alpha- and d-subunits in synchronous liver metastasis compared
      with primary tumor and normal mucosa, respectively. ATP synthase alpha- and d
      subunits were overexpressed in 197 (78.5%) and 190 (75.7%), respectively, of the
      251 colorectal cancers. The alpha- and d-subunits were significantly associated
      with liver metastasis (P < 0.05) as well as low histological grade (P < 0.0001).
      The d-subunit also correlated with venous invasion (P = 0.026) and distant
      metastasis (P = 0.032). In stage III cancers, d-subunit expression was
      independently associated with poor survival (P = 0.017). Furthermore,
      transfection of small interfering RNA targeted to ATP synthase alpha- and d
      subunits resulted in decreased in vitro invasiveness of the human colon cancer
      cell line. Our overall findings demonstrate that increased ATP synthase is
      associated with liver metastasis of colorectal cancer.

PMID- 17559426
TI  - Increased sickness absence in diabetic employees: what is the role of co-morbid
      conditions?
AB  - AIMS: Diabetes is thought to be associated with increased risk of sickness
      absence in working populations. We examined the contribution of co-morbidity to
      this association. METHODS: Records of physician-certified sickness absence
      episodes (> 3 days) over a 1-year period were obtained from employers' records
      after a survey of chronic diseases and risk factors in 638 diabetic and 32 510
      non-diabetic public sector employees in Finland (the Public Sector Study).
      RESULTS: Diabetic employees had a 2.15-fold (95% confidence interval 1.92-2.40)
      age- and sex-adjusted excess risk of sickness absence compared with their
      colleagues with no chronic disease. In absolute terms, diabetes was related to 59
      extra absence episodes per 100 person years. Of this excess risk, 55% was
      attributable to co-occurring non-cardiovascular diseases, such as depression,
      prolapsed intervertebral disc and bronchitis. The contribution of cardiovascular
      complications to the excess sickness absence was small (7%). CONCLUSIONS: In this
      occupational cohort, the excess risk of sickness absence in diabetic employees
      was largely accounted for by non-cardiovascular co-morbidity. Intervening
      multiple chronic conditions may be important in programmes to reduce sickness
      absence in diabetic employees.

PMID- 17559427
TI  - Plasma endothelin response to acute hypoglycaemia in adults with Type 1 diabetes.
AB  - AIMS: To determine whether acute insulin-induced hypoglycaemia provokes a
      detectable alteration in peripheral plasma endothelin (ET) concentrations in
      humans with Type 1 diabetes. METHODS: Serial plasma concentrations of ET were
      measured in 20 patients with Type 1 diabetes during controlled hypoglycaemia
      induced by intravenous infusion of soluble insulin. RESULTS: A significant
      increase was observed in plasma ET concentrations, from 3.80 +/- 0.31 pg/ml at
      baseline to 6.72 +/- 1.47 pg/ml at 60 min after the onset of the hypoglycaemic
      reaction (P < 0.05). CONCLUSIONS: Acute insulin-induced hypoglycaemia induces a
      rise in plasma endothelin concentrations in people with Type 1 diabetes. This
      finding is consistent with a putative role for ET in the mediation of
      hypoglycaemia-induced vasoconstriction, and the possible precipitation of
      macrovascular or microvascular events.

PMID- 17559428
TI  - Endothelial dysfunction, ambulatory pulse pressure and albuminuria are associated
      in Type 2 diabetic subjects.
AB  - AIM: Elevated pulse pressure (PP) is associated with microvascular complications
      in Type 2 diabetic patients. In non-diabetic subjects, elevated PP has been
      associated with endothelial dysfunction. The relation between endothelial
      dysfunction and PP in diabetic subjects has not previously been examined. We
      examined the relation between PP, markers of endothelial activation and
      albuminuria in Type 2 diabetic patients. METHODS: In 46 Type 2 diabetic patients
      and 19 non-diabetic subjects, we performed 24-h ambulatory blood pressure (AMBP)
      monitoring. Urinary albumin excretion rate was measured as three urinary
      albumin/creatinine ratios. Von Willebrand factor (vWF), fibrinogen, E-selectin
      and soluble intercellular adhesion molecule 1 (ICAM-1) were measured in plasma.
      RESULTS: Thirty-four patients had normoalbuminuria (group N) and 12 had micro- or
      macroalbuminuria (group A). PP levels increased in a stepwise manner from the
      control group (group C) to group N and group A; night PP 43 +/- 5, 48 +/- 10 and
      59 +/- 12 mmHg (groups C, N and A, respectively, P < 0.001). Likewise, plasma
      levels of vWF, fibrinogen, E-selectin and ICAM-1 increased from group C to group
      A; e.g. ICAM-1 [median (interquartile range)] 191 (160-217), 213 (189-262) and
      316 (260-417) ng/ml, groups C, N and A, respectively, P < 0.001). In diabetic
      patients, night PP and plasma levels of E-selectin and ICAM-1 correlated (r =
      0.38, P < 0.01 and r = 0.37, P = 0.01, night PP with E-selectin and ICAM-1,
      respectively). CONCLUSION: Increased PP is associated with endothelial activation
      and albuminuria in Type 2 diabetic patients. Thus, endothelial dysfunction may
      represent a pathophysiological link between an elevated PP and microvascular
      complications in these subjects. Prospective studies are needed to further
      elucidate these associations.

PMID- 17559429
TI  - The association between baseline characteristics and the outcome of foot lesions
      in a UK population with diabetes.
AB  - AIMS: To explore the relationships between time to healing of diabetic foot
      ulcers and baseline characteristics of both patients and their ulcers. METHODS:
      All patients were included who were referred to a specialist clinic over a 4-year
      period. Age, gender, type and duration of diabetes, ulcer site, ulcer duration
      and baseline characteristics were recorded. Postcode was used to derive an index
      of social deprivation. Patients were followed up to 1 year. The primary outcome
      measure was time to healing. Those who died or had an ulcer-related amputation
      were censored at the time of death or amputation and classified as unhealed.
      RESULTS: Mean age of 449 participants (63.7% male) was 66.7 years; 42.7% had
      evidence of peripheral arterial disease, and 80% had peripheral neuropathy.
      Median ulcer duration at presentation was 29 days; 60.5% ulcers had an area of <
      1 cm(2) and 68.3% of all ulcers healed without amputation during the follow-up
      period. Univariate analysis revealed dose-response relationships between time to
      healing and increasing duration of diabetes, increasing ulcer area, ulcer site
      and peripheral arterial disease. No associations were found with age, gender,
      diabetes type, deprivation index, peripheral neuropathy or infection. The
      relationship between healing time and ulcer area, peripheral arterial disease and
      diabetes duration remained significant on multivariate analysis. CONCLUSIONS: The
      dominant factors influencing healing are cross-sectional area at presentation and
      the degree of peripheral arterial disease. Further work is needed to define how
      those at greatest risk may be identified and best managed.

PMID- 17559430
TI  - When is a technically successful peripheral angioplasty effective in preventing
      above-the-ankle amputation in diabetic patients with critical limb ischaemia?
AB  - AIM: To determine parameters predictive of avoidance of major (above-the-ankle)
      amputation after a technically successful peripheral angioplasty (PTA) in
      patients with diabetes with critical limb ischaemia. METHODS: From January 1999
      to December 2003, 420 consecutive patients with diabetes admitted to hospital
      because of critical limb ischaemia underwent peripheral angiography and
      concomitant technically successful PTA. Transcutaneous oxygen tension (TcPO(2))
      was measured before and after PTA. Major amputation at 30 days was recorded.
      RESULTS: After PTA, the iliac-femoral-popliteal axis was patent in all patients.
      In 67 patients, all three crural arteries were patent, in 143 patients 2 crural
      arteries were patent, and in 186 patients one crural artery was patent (104
      peroneal, 62 anterior tibial, 20 posterior tibial). In 24 patients, all three
      crural arteries were occluded. Twenty-two major amputations were performed. Of
      these, 15 were performed in the 24 patients with occlusion of all the
      infrapopliteal arteries. Seven of the 186 patients in whom only the peroneal
      artery was patent required amputation. In patients not requiring amputation,
      TcPO(2) increased from 15.5 +/- 11.9 to 45.0 +/- 12.0 mmHg (P = 0.000), while in
      those requiring amputation, TcPO(2) increased from 9.6 +/- 7.7 to 18.6 +/- 8.1
      mmHg (P < 0.082). Multivariate analysis indicated an independent role of
      occlusion of infrapopliteal arteries after PTA (OR 8.20 for every crural
      obstructed artery, P = 0.022, CI 1.35-49.6) and TcPO(2) after PTA (OR 0.80 for
      increase of 1 mmHg, P < 0.001, CI 0.74-0.88). CONCLUSIONS: In patients with
      diabetes, PTA is effective in avoiding major amputation, provided recanalization
      occurs in at least one tibial artery down to the foot. In a few patients, re
      canalization of the peroneal artery alone is not sufficient to avoid major
      amputation.

PMID- 17559432
TI  - Experienced dilemmas of everyday life in chronic neuropathic pain patients-
      results from a critical incident study.
AB  - Neuropathic pain is a disabling chronic condition with limited therapeutic
      options. Few studies have addressed patient's experience and strategies. The aim
      of this study was to explore dilemmas experienced in order to improve care and
      rehabilitation. An interview study with 39 patients suffering from neuropathic
      pain of different origin was performed. We used the critical incident technique
      to collect data. Questions on occasions when patients had been hindered by or
      reminded of their neuropathic pain were included, and the self-perceived
      consequences and management of such occasions. The interviews were transcribed
      verbatim and analysed qualitatively. A broad range of experiences categorised
      into dilemmas, disturbances, consequences and managements from most parts of
      everyday life was identified. The dilemmas were 'housework', 'sitting', 'physical
      activity', 'personal hygiene', 'sleeping difficulties', 'hypersensitivity to
      external stimuli', 'social relationships', 'transportation' and 'leisure time'.
      Disturbances were 'failures', 'inabilities' and 'restrictions'. Consequences were
      'increased pain', 'psychological reactions' and 'physical symptoms'. The majority
      of the patients used activity-oriented strategies to manage their pain such as
      alternative ways of performing the task, a cognitive approach or simply ignoring
      the pain. This is one of the first studies presenting detailed data on everyday
      dilemmas, disturbances and consequences of patients with chronic neuropathic
      pain. Such information is important in clinical settings to improve care and
      rehabilitation.

PMID- 17559433
TI  - Meanings of being a female co-worker to a person developing burnout.
AB  - Burnout is dramatically increasing in many industrialised countries. Burnout is
      mainly studied from the perspective of the burnout person although it has been
      confirmed to affect co-workers as well. This study aimed to illuminate meanings
      of being a female co-worker to a person developing burnout. Fifteen interviews
      with nursing and medical staff were performed, tape-recorded and transcribed
      verbatim and a phenomenological-hermeneutic method was used to interpret the
      text. One meaning of being a female co-worker is struggling, on the one hand to
      understand and help the person developing burnout and on the other hand to manage
      their work and survive oneself. This means to be torn between helping the
      workmate and managing their work. Co-workers are filled with contradictory
      feelings, from deep concern to aversion and when the workmate finally goes on
      sick leave, co-workers' feelings of shortcomings and failure emerge, along with
      troubled conscience. This study reveals a picture of the difficulties of being a
      female co-worker to a person developing burnout that it is crucial to be aware
      of.

PMID- 17559434
TI  - Quantification of the pain terms hurt, ache and pain among nursing students.
AB  - The aim of this study was to determine the quantitative meaning nursing students
      ascribe to the pain terms hurt (ont), ache (vark) and pain (smarta). In total,
      549 nursing students filled in a questionnaire including questions about age,
      gender, and health care work experience. The students were also requested to rate
      response using a Visual Analogue Scale (VAS) rating for different statements
      about hurt, ache and pain. The results show that there were significant
      differences (p < 0.001) between rated intensity of the statements of hurt, ache
      and pain. There were, however, large variations in the students' ratings of the
      pain terms; hurt ranged from 3 to 97 mm, ache from 7 to 97 mm and pain from 27 to
      100 mm. There were no significant differences between male and female students
      regarding their ratings of hurt and ache when they were used to describe the
      worst self-experienced pain. Female students rated their experience of pain
      significantly higher (p < 0.001) on the VAS compared with male students. There
      was no significant correlation between previous experience of health care work
      and rated intensity of hurt, ache and pain. In conclusion, this study shows that
      there exist significant differences between the pain terms hurt, ache and pain
      according to a rating on a VAS. However, the results also demonstrate that there
      are large individual variations in how the students quantify the fictitious
      patient statements of hurt, ache and pain.

PMID- 17559435
TI  - Work satisfaction, career preferences and unpaid household work among recently
      graduated health-care professionals--a gender perspective.
AB  - AIM: This study investigated perceptions of recently graduated health-care
      professionals towards healthcare work, preferences for future careers, work
      organisation and management. In addition, it scrutinised the impact of unpaid
      household work on work satisfaction using a gender theoretical analysis. METHOD:
      A questionnaire was distributed to 1035 nurses, occupational therapists and
      physiotherapists who graduated in the semester of spring 1999 in Sweden. The
      response rate was 81% and the respondents represent 3338 graduates. When
      estimating proportions and means, sampling weights reflecting the sampling design
      were used. RESULTS: Among both men and women, there was a high satisfaction with
      work in general, but a great dissatisfaction with work management and
      organisation. Multiple logistic regression analyses revealed a significant
      association between dissatisfaction with the work organisation and age groups and
      type of employment among the women. Younger women were more dissatisfied than
      older, and public employees were more dissatisfied than private employees. The
      women in the study did more unpaid household work than the men did. The data
      suggest that this can be of importance for the dissatisfaction at work, although
      this was not statistically significant. Working conditions and career preferences
      differ between the three professions as well as among men and women in the same
      profession. Geriatrics was not a preferred area for future work, although it is
      an area with predicted increasing personnel needs in the future. The results are
      discussed in relation to future needs for health-care personnel, gender and
      organisation theory. CONCLUSIONS: Because of the predicted scarcity of health
      care personnel in Sweden, it is of importance that healthcare organisations
      address the issues of work satisfaction as well as possible competence drain.
      Gender equality in terms of working conditions is another important aspect that
      needs to be highlighted.

PMID- 17559436
TI  - Quality of life of elderly persons with cancer: a 6-month follow-up.
AB  - The aim of this study was to investigate possible changes in quality of life
      (QoL) in elderly persons diagnosed with cancer (65 years and above), in relation
      to age, contact with the health-care system, activities of daily living, hope,
      social network and support. The investigation points were at time of diagnosis
      (baseline), and again 3 and 6 months after the diagnosis. The study also aimed to
      investigate which of the aforementioned factors predicted deteriorated QoL in
      elderly persons with cancer from baseline to the 6-month investigation. At
      baseline, the sample consisted of 101 individuals aged (age 65+) recently
      diagnosed with cancer (74 women, 27 men), but was reduced to 75 (57 women, 18
      men) by the 6-month investigation point. EORTC QLQ C30, Katz ADL, Nowotny's Hope
      Scale and Interview Schedule for Social Interaction were used in structured
      personal interviews and questionnaires. Emotional function improved significantly
      over time, and complaints of nausea and vomiting decreased. Contact with a
      district nurse at baseline predicted deteriorated QoL from baseline to 6 months
      later. Support from grandchildren increased significantly. About 30% of the total
      sample deteriorated in QoL, by the significant >/=10 units, from baseline to 6
      month follow-up, while about 70% remained stable in QoL from baseline. The
      majority of the elderly persons with cancer showed an ability to adjust to the
      new condition. However, in clinical practice, specific attention should be paid
      to the most vulnerable groups of elderly persons with cancer: those with advanced
      disease and decreased hope, and those with increased need of both informal and
      formal assistance.

PMID- 17559437
TI  - Virtue and health--finding meaning and joy in working life.
AB  - The perspective of this investigation is the humanistic caring tradition of
      caring science where caritas motive, i.e. charity and love, constitutes the basic
      motive and suffering the basic category of caring, i.e. Eriksson's theory of
      caritative caring. The concept of virtue is used in accordance with Aristotle's
      theory of virtue and fragments of theory are added to the study from Arendt. The
      aim of the study was to investigate the meaning of virtues for worker's health
      and to develop a theoretical model of the inner health domains. The investigation
      comprises an empirical study using focus-group interviews for the collection of
      data. The participants were 16 employees, in four focus groups, in the wood
      processing industry. The study was conducted from September 1999 to January 2000.
      Hermeneutical interpretation has been used in the search for a deeper
      understanding of the connection between virtue and health in working life.
      Abduction is the conclusion method, which is used in this study. The result is
      presented at four levels of interpretation and the final findings constitutes
      four theses which comprise the virtues of pride, generosity, love and honesty as
      important in working life and a theoretical model comprising three dimensions:
      the innermost dimension, the middle dimension and the outer dimension. These
      dimensions reflect health as becoming. By means of virtues it is possible to find
      the way to the inner domains of health. Pride as a virtue and how it is heeded at
      work, is decisive in determining whether health becomes discernable in working
      life and the value, i.e. found in pride is decisive when it comes to the
      employee's conception of the meaning of work. The study shows that the connection
      between health and virtue is important to recognize. This approach points out
      underlying values that effects worker's health.

PMID- 17559438
TI  - Health-related quality of life-testing the reliability of the MSQOL-54 instrument
      among MS patients.
AB  - The purpose of the study was to assess the reliability of the specific multiple
      sclerosis quality of life (MSQOL-54) instrument, which contains 54 items
      measuring quality of life, among Finnish multiple sclerosis (MS) patients.
      Nursing professionals evaluated the clarity and comprehensibility of the
      translated instrument, after which it was pilot-tested. The data were collected
      through a questionnaire survey in the spring 2004. Persons diagnosed with MS in
      1999-2001 filled in the questionnaire (n = 100). The response percentage was 81%.
      The structural validity of the MSQOL-54 instrument was evaluated with factor
      analysis and the generic 15D quality of life instrument. The internal consistency
      of the instrument was measured with Cronbach's alpha, correlations and item
      analysis. According to the results, the structural validity of MSQOL-54 was good,
      and factor analysis yielded a clear-cut factorial model. More than half of the
      correlations between the comparable items of the 15D and MSQOL-54 instruments
      were moderate or better. The internal consistency of MSQOL-54 can hence be
      considered quite good: Cronbach's alpha coefficients calculated for the factors
      and their items ranged within 0.33-0.89. The alpha coefficient calculated for the
      whole instrument was 0.84. The internal consistency of MSQOL-54 was further
      confirmed by the results of an item analysis, which showed the correlation
      coefficients between the items of the different dimensions to be good (0.31
      0.81). On the basis of the test results, the MSQOL-54 instrument is fairly
      reliable and suitable for assessing the health-related quality of life of MS
      patients. The reliability of MSQOL-54 should be evaluated further by a
      longitudinal study design in the future.

PMID- 17559439
TI  - The role of paradoxical beliefs in chronic pain: a complex adaptive systems
      perspective.
AB  - The biological sciences have contributed an extensive volume of research in
      efforts to resolve chronic pain, and an expanding body of research focusing on
      the psychosocial aspects of chronic pain, is now also evident. Paradigms applied
      to chronic pain appear to compete and lack an integrative framework. This paper
      builds a case for framing chronic pain within a complex adaptive systems (CAS)
      paradigm and explores how paradox, one of the key features of a CAS, contributes
      to maintaining 'chronicity' in the system. A complexity science paradigm can
      serve as a meta-framework, integrating theoretical models employed in chronic
      pain and reframing dissent and conflict as positive generative forces for change.
      Interventions, based on complexity science principles, can effect change in the
      highly interactive systems that constitute the chronic pain experience.

PMID- 17559440
TI  - Satisfaction and coercion among voluntary, persuaded/pressured and committed
      patients in acute psychiatric treatment.
AB  - RATIONALE: Whereas the distinction between committed and voluntary admissions in
      mental health is clear from a legal point of view, this clarity is not always
      present in the patients' experiences. Voluntary patients may be pressured or
      persuaded and committed patients may want admission. AIMS: To compare three
      groups of patients--committed, voluntary and persuaded--admitted to acute
      psychiatric inpatient care as regards different aspects of satisfaction,
      treatment and experienced coercion. METHOD: The Sjukvardens Planerings- och
      Rationaliseringsinstitut form and the Coercion Ladder were administered to all
      admitted patients on two acute wards. A total of 189 patients participated (86%).
      Data were analysed with nonparametric (Kruskal-Wallis, chi-square) and parametric
      tests (multinominal regression). RESULTS: A substantial proportion of the
      patients did not know of their legal status. Many reported restrictions on
      movement, forced medication and patronising communication. Satisfaction with the
      treatment was generally high. Compared to the voluntary patients, the two other
      groups were characterized by lack of influence, forced medication and high
      satisfaction with the key worker. CONCLUSION: Involuntariness was associated with
      increased likelihood of feeling excluded from participation in the treatment. The
      key worker seems to have an important position with regard to committed and
      pressured patients. LIMITATIONS: The data were limited to the patients'
      subjective reports.

PMID- 17559441
TI  - Central concepts in the midwife-woman relationship.
AB  - The relationship between the midwife and the woman is essential for a positive
      experience for woman during childbearing period, i.e. pregnancy, childbirth and
      the first postpartum phase. Thereby, the aim of this study was to delineate
      central concepts in the midwife-woman relationship, in normal as well as high
      risk situations. A secondary analysis was performed on original texts from eight
      Swedish qualitative studies, all with a phenomenological or phenomenological
      hermeneutic approach. Six pairs of concepts were elucidated; each one describing
      one aspect from the woman's perspective and one responsive aspect from the
      midwife. The pairs of concepts are: surrender-availability, trust-mediation of
      trust, participation-mutuality, loneliness-confirmation, differenceness-support
      uniqueness and creation of meaning-support meaningfulness. Disciplinary concepts
      about the midwife-woman relationship have evolved that are essential for care in
      both normal and high-risk contexts, and we suggest that they should be
      implemented as a guide for midwifery care.

PMID- 17559442
TI  - Psychometric properties of the Swedish version of the Resilience Scale.
AB  - The aim of this study was to investigate resilience in relation to age and
      gender, and to elucidate the underlying structure of the Swedish version of the
      Resilience Scale (RS). The RS, originally created by Wagnild and Young is a 25
      items scale of Lickert type with possible scores ranges from 25 to 175, the
      higher the score, the stronger resilience. A standardized procedure was used for
      translation. The analysis was based on 1719 participants, 1248 women and 471 men,
      from eight different samples, aged from 19 to 103 years. We found that the
      participants estimated their resilience as relatively high. There was a
      significant relationship between age and resilience, for every year RS score
      increased with 0.134 units. There was no relation between gender and resilience.
      From a factor analyses five factors emerged, equanimity, meaningfulness,
      perseverance, existential aloneness and self-reliance reflecting the five
      dimensions described by Wagnild and Young. We concluded that the resilience is
      related to age, the older, the stronger resilience. Five underlying dimensions
      was identified, which can be seen as reflection of the theoretical assumptions
      behind the RS scale. The RS scale seems applicable to a Swedish population.

PMID- 17559443
TI  - A life enriching togetherness--meanings of informal support when being a parent
      of a child with disability.
AB  - The majority of children affected by disability are cared for at home by their
      parents. It is well documented in research literature that the parents are in
      need of professional support. In the striving to improve the professional caring,
      it is also important to deepen our understanding about the meaning of informal
      support from the perspective of parents' life world. The aim of this study was to
      illuminate the meanings of lived experience of informal support, when being a
      parent of a child affected by disability. Thirteen parents, eight mothers and
      five fathers within eight families, participated in narrative interviews, which
      were analysed by using a phenomenological-hermeneutic method. The meanings
      resulted in three themes: 'being gratified by experiences of the child as having
      a natural place in relation with others', 'being provided a room for sorrow and
      joy' and 'being enabled to live an eased and spontaneous daily life'. These
      themes emanated from the experiences of other persons' being and doing in
      relation to the parents, the child affected by disability and the siblings.
      According to our interpretation, informal support means a life enriching
      togetherness, the core of which is natural human caring. The findings also showed
      that parents highly valued professional support concerning informal supporters.

PMID- 17559444
TI  - Psychometric properties of the Swedish Diabetes Empowerment Scale.
AB  - OBJECTIVE: This study was conducted to determine the psychometric properties of
      the Swedish version of the Diabetes Empowerment Scale (Swe-DES-23). RESEARCH
      DESIGN AND METHODS: A convenience sample of 195 patients with type 1 and type 2
      diabetes completed the Swe-DES-23 questionnaire. To establish discriminant
      validity, Swe-DES subscales were compared with the Semantic Differential in
      Diabetes scale (SDD) and a general health scale (EVGFP). Construct validity was
      tested using factor analyses. To determine unidimensionality of the subscales,
      inter-item correlations were calculated. Internal consistency was tested by the
      use of the Crohnbach-alpha coefficient. RESULTS: The factor analysis resulted in
      four factors (empowerment subscales) with eigenvalues >1.0, explaining 60% of the
      variance. The four empowerment subscales: goal achievement, self-awareness,
      stress management and readiness to change showed Crohnbach-alpha values ranging
      from 0.68 to 0.91. Patients with good self-reported health and low burden of
      diabetes scored significantly higher on almost all empowerment subscales. Only
      weak correlations were found between metabolic control and the empowerment
      subscales. CONCLUSIONS: The SWE-DES-23 scale had acceptable validity and
      reliability and, thus, could be a suitable tool in evaluating empowerment-based
      education programmes. Further testing is needed to shorten the questionnaire.

PMID- 17559445
TI  - A network-based rehabilitation model for frail elderly people: development and
      assessment of a new model.
AB  - INTRODUCTION AND PURPOSE: Living independently at home promotes the well-being of
      people aged 65 and over. In Finland, the municipalities are responsible for
      providing social and health services, including rehabilitation of the elderly.
      Rehabilitation is in practice carried out by independent rehabilitation centres.
      The Social Insurance Institution of Finland is a national agency responsible for
      financing and developing rehabilitation. Combining the efforts of these three
      agencies, a new network-based inpatient rehabilitation model was established to
      support the community living of frail elderly persons at high risk of
      institutionalization. This article describes the new model and evaluates the
      cooperation within the rehabilitation network, as well as the contents of the
      rehabilitation. MATERIAL AND METHODS: The new model was evaluated in two phases
      using diverse methods. First, the networks were assessed as they were being
      established in 2000, and secondly, when they were operational in 2002. The first
      phase involved 53 networks operating in 46 municipalities and 12 rehabilitation
      centres, and the second 44 networks in 41 municipalities and seven rehabilitation
      centres. The data were collected by questionnaires, interviews and reports.
      RESULTS: The rehabilitation networks were functional, although constant
      development and search for better working practices was time consuming. Two
      different approaches in the networks were found: the 'networks of creators' were
      able to carry out the new tasks highly successfully, while the 'networks of
      followers' only managed to do the minimum as instructed. Motivated network
      members and adequate resources appeared to be essential for a successful
      rehabilitation process. CONCLUSIONS: It is possible to create a functional
      rehabilitation network involving different agencies. Further development work is
      necessary to make the network-based rehabilitation model more efficient.

PMID- 17559446
TI  - Self-assessed occupational health and working environment of female nurses, cabin
      crew and teachers.
AB  - AIM: The aim of this study was to describe and compare the self-assessed
      occupational health among female nurses, cabin crew and teachers, in relation to
      their working environment. BACKGROUND: Similarities between the three
      occupations, i.e. predominantly female and service-oriented, render them
      interesting in comparison with respect to health and working environment.
      METHODS: The participants were female Icelandic cabin crew, nurses and elementary
      school teachers. A questionnaire including items on socio-demographics, working
      environment (addressing work pace, job security, monotonous work, assistance,
      physically strenuous work and physical environmental factors) and a symptom list
      was used for data collection. Factor analyses on the symptom list resulted in
      five symptom scales: Musculoskeletal, Stress and exhaustion, Common cold,
      Gastrointestinal and Sound perception scale. A total of 1571 questionnaires were
      distributed. The response rate was 65.7-69%, depending on occupation. Data were
      collected in 2002. RESULTS: Cabin crew reported worse gastrointestinal, sound
      perception and common cold symptoms than nurses and teachers. Cabin crew and
      teachers reported worse symptoms of stress and exhaustion than nurses (p < 0.05).
      When compared with teachers and nurses cabin crew reported less job security and
      more physically strenuous and monotonous work. Nurses were likelier to seek
      assistance from co-workers or patients as well as to take care of an older
      relative than teachers and cabin crew. Regression analysis found that within each
      occupation distress from environmental factors resulted in higher score on all
      the symptom scales. CONCLUSIONS: Nurses experience less stress and exhaustion
      than teachers and cabin crew. In comparison with one or both of the other
      occupations nurses are more likely to assist each other with their work,
      experience job security, reporting physically complex work and take care of older
      relatives. This should be highlighted as positive aspects of nurses' work praised
      as displaying responsibility and interconnectedness of nurses'.

PMID- 17559447
TI  - Experiences of surviving spouse of terminally ill spouse: a phenomenological
      study of an altruistic perspective.
AB  - The aim of the study was to illuminate the experiences of surviving relatives in
      connection with their care at home of terminally ill, dying spouses, followed by
      an outline of the need for palliative assistance by the district nurse.
      Qualitative interviews with eight surviving relatives have been analysed on the
      basis of the phenomenological method. The essence of these phenomena was the
      loving promise to the terminally ill and dying spouse in which the shared grief,
      structural disintegration and powerlessness, lifelines and supporters and viable
      grief appeared. This promise consisted of that dying spouse will be able to stay
      at home during the illness and his or her desire to die at home. It was given
      during uncomfortable hospitalization and springing from the spouse's desire for
      autonomy and integrity at the end of his or her life. In keeping the promise, the
      surviving spouse became altruistic, neglecting his or her own primary needs in
      the unselfish fulfilment of the needs of the terminally ill spouse. The surviving
      spouse grieved in lonely isolation characterized by stress and an ethical dilemma
      in connection with breaching the promise. Light was shed on the professional
      palliative care with the surviving spouse's lacking verbalization of grief and
      powerlessness, regardless of whether expert professional palliation or
      insufficient professional palliation was provided. In that way the findings of
      the study showed the necessity for professional involvement in the decision
      concerning palliation at home, including identification of the resources of the
      primary caregiver.

PMID- 17559448
TI  - A patient-oriented perspective in existential issues: a theoretical argument for
      applying Peplau's interpersonal relation model in healthcare science and
      practice.
AB  - Since Hildegard Peplau's interpersonal relation model for psychodynamic nursing,
      in the 1950s, many theories about humanity have been expanded in the discipline
      of nursing. For this purpose Rosemarie Rizzo Parse, for example, synthesized
      principles and concepts from Martha Rogers with existential phenomenology, when
      she introduced the idea of a simultaneity paradigm as unique for the discipline
      of nursing in opposition to Peplau's psychodynamic model. The aim of this paper
      is to discuss borrowed theories in relation to the efforts to find a unique
      theoretical foundation for healthcare science and practice. It is suggested that
      Parse's division in a totality vs. a simultaneity paradigm is an artificial
      distinction. The discussion is concluded with reflections about Peplau's
      interpersonal relation model, a patient-oriented perspective and psychodynamic
      theory, as example of a theory, which may help to further understand patients'
      existential situation.

PMID- 17559449
TI  - Are sugars-free medicines more erosive than sugars-containing medicines? An in
      vitro study of paediatric medicines with prolonged oral clearance used regularly
      and long-term by children.
AB  - OBJECTIVE: The reduced use of sugars-containing (SC) liquid medicines has
      increased the use of other dose forms, potentially resulting in more widespread
      dental effects, including tooth wear. The aim of this study was to assess the
      erosive potential of 97 paediatric medicines in vitro. METHODS: The study took
      the form of in vitro measurement of endogenous pH and titratable acidity (mmol).
      Endogenous pH was measured using a pH meter, followed by titration to pH 7.0 with
      0.1-M NaOH. RESULTS: Overall, 55 (57%) formulations had an endogenous pH of <
      5.5. The mean (+/- SD) endogenous pH and titratable acidity for 41 SC
      formulations were 5.26 +/- 1.30 and 0.139 +/- 0.133 mmol, respectively; for 56
      sugars-free (SF) formulations, these figures were 5.73 +/- 1.53 and 0.413 +/-
      1.50 mmol (P > 0.05). Compared with their SC bioequivalents, eight SF medicines
      showed no significant differences for pH or titratable acidity, while 15 higher
      strength medicines showed lower pH (P = 0.035) and greater titratable acidity (P
      = 0.016) than their lower-strength equivalents. Chewable and dispersible tablets
      (P < 0.001), gastrointestinal medicines (P = 0.002) and antibiotics (P = 0.007)
      were significant predictors of higher pH. In contrast, effervescent tablets (P <
      0.001), and nutrition and blood preparations (P = 0.021) were significant
      predictors of higher titratable acidity. CONCLUSIONS: Paediatric SF medicines
      were not more erosive than SC medicines in vitro; a more significant predictor of
      their erosive potential was dose form.

PMID- 17559450
TI  - Influence of local anaesthesia on the quality of class II glass ionomer
      restorations.
AB  - OBJECTIVE: To investigate the influence of local anaesthesia on the quality of
      class II glass ionomer restorations with discomfort as cofactor. MATERIAL AND
      METHODS: The study population consisted of 6- to 7-year-old schoolchildren in
      Paramaribo and its environs. To be included, each child needed to have a
      proximally situated cavity in a primary molar that was accessible to hand
      instruments and where no pulp exposure was expected. They were randomly divided
      into four treatment groups: conventional method with and without local
      anaesthesia and atraumatic restorative treatment method (ART) with and without
      local anaesthesia. The restoration quality was scored using the evaluation
      criteria for ART restorations (successful if restoration is correct or has a
      minor defect and fails if defects are larger than 0.5 mm, if secondary caries is
      observed, if the restoration is fractured, partly or totally lost or if the pulp
      is involved) at 6 and 30 months after treatment. The extent of discomfort was
      registered by assessing the behaviour (modified Venham score) and observing the
      heart rate during treatment. RESULTS: For this study 153 children were treated
      with hand instruments (ART) and 146 children with rotary instruments
      (conventional method). A total of 198 restorations were evaluated during follow
      up periods. There were no significant differences in patient discomfort between
      the ART and the conventional group and between the anaesthesia and the non
      anaesthesia group. The conventional restorations demonstrated significantly
      higher success rates than ART restorations after 6 (P = 0.001) and 30 months (P =
      0.032). There were no significant differences in success rate between the
      anaesthesia and the non-anaesthesia group. CONCLUSION: Local anaesthesia has no
      influence on discomfort during treatment. Furthermore, discomfort during
      treatment does not affect the success rate of restorations.

PMID- 17559451
TI  - A retrospective study of paediatric oral lesions from Thailand.
AB  - AIM: To survey the paediatric oral lesions in Thailand. DESIGN: Biopsy records
      over a 15-year period (1990-2004) were retrieved from the files of the Department
      of Oral Pathology, Faculty of Dentistry, Chulalongkorn University. Paediatric
      cases with an age of 16 years or younger were selected. The age of the patients
      was divided into three groups according to the dentition period. The lesions were
      classified into three categories: inflammatory/reactive lesions, cystic lesions,
      and tumour/tumour-like lesions. RESULTS: From a total of 8314 oral biopsies, 1251
      cases (15.05%) were in the paediatric population. The greatest number of lesions
      fell into the cystic category, followed closely by the inflammatory/reactive
      category and tumour/tumour-like category, respectively. The top ten most
      frequently encountered lesions in the present study were dentigerous cyst,
      mucocele, pyogenic granuloma, ameloblastoma, radicular cyst, odontoma,
      odontogenic keratocyst, irritation fibroma (focal fibrous hyperplasia), fibrous
      dysplasia, and osteomyelitis. The majority of lesions were found in the mixed
      dentition period (49.24%). There was no statistical difference in the occurrence
      between genders in this study. CONCLUSIONS: The present study shows an almost
      similar trend to previous studies except in the ranking among and within
      categories. These differences may be attributable to the nature of the population
      studied and because Chulalongkorn University is a major referral centre.

PMID- 17559452
TI  - The role of MSX1 in tooth agenesis in Iranians.
AB  - INTRODUCTION: MSX1 gene has a critical role in craniofacial development, the aim
      of this case-control study is to test the hypothesis that MSX1 mutation
      contributes to congenital tooth agenesis in Iranians. MATERIALS AND METHODS: The
      study group consisted of 20 affected individuals with tooth agenesis of lower
      second premolars or upper lateral incisors with mean age of 24.6. The control
      group consisted of 20 unaffected individuals. DNA was extracted from all 40
      individuals; the polymerase chain reaction (PCR) for MSX1 was carried out with
      Phenol: Chloroform: Isoamylalchol (PCI) extraction method. Ban II restriction
      digest and agarose gel electrophoresis of the 20 affected individuals verified
      the presence of mutation in all 20 affected individuals. The unaffected controls
      did not show any mutation. Statistical analysis performed by the chi-squared
      method. RESULTS: Ban II did not digest PCR product (DNA) in the control group
      (195 bp band on electrophoresis gel) but digested the affected allele (106 bp and
      89 bp bands). There is a statistically significant correlation between tooth
      agenesis and MSX1 mutation (P < 0.001). CONCLUSION: The results indicated that
      MSX1 gene mutation contributes to tooth agenesis in Iranian individuals. As the
      timing of tooth calcification can vary, radiographic finding of congenital tooth
      agenesis can be confirmed by this molecular method during different dental ages
      to achieve certainty.

PMID- 17559453
TI  - Severely hypoplastic amelogenesis imperfecta with taurodontism.
AB  - BACKGROUND: The prominent dental feature of a boy was severely hypoplastic enamel
      in both primary and permanent teeth. CASE REPORT: Many permanent teeth were
      already infected while emerging in the oral cavity. Panoramic radiograph showed
      enlarged and elongated pulp chambers (taurodontism) in the permanent first
      molars. The clinical and radiological diagnosis was either hypomaturation
      hypoplastic amelogenesis imperfecta with taurodontism (AIHHT) or tricho-dento
      osseous syndrome (TDO). Histological examination of the upper right permanent
      first molar revealed thin lamellar or somewhat thicker amorphous enamel on
      approximal surface only with no rods or incremental lines visible.
      Histologically, the Witkop type AIG designated 'enamel agenesis' cannot be
      excluded. The medical and dental history of the family members, as well as the
      boy's medical examination, was noncontributing. He had thick, blond, curly hair.
      The bone structure of the jaws and skull was normal. For genetic analysis, DLX3
      gene was sequenced but no mutation was found. CONCLUSIONS: Since the gene defect
      of TDO has been localized only in the DLX3 gene, the more probable diagnosis was
      AI.

PMID- 17559454
TI  - Use of a ranked scoring system to detect occlusal caries in primary molars.
AB  - OBJECTIVE: The available literature concerning systems for occlusal caries
      detection in primary teeth is limited. The aim of this study was to compare in
      vitro a ranked scoring system for occlusal caries detection in primary molar
      teeth with bitewing radiography and to investigate the most accurate cut-off
      point for dentine caries detection when using this ranked scoring system.
      METHODS: Sixty primary molar teeth were examined in vitro visually and by
      bitewing radiography (two examiners) using Ekstrand' criteria. RESULTS:
      Histological examination revealed that 13% were sound, 38% had enamel caries and
      the remainder had dentine caries. Similar accuracy was seen when comparing
      bitewing radiographs and visual examination for caries detection at the d3
      threshold, while visual examination was more accurate at the d1 threshold. The
      most suitable cut-off for diagnosing caries at the d1 threshold was V1 (no/slight
      change in enamel translucency after air drying). Either V2 (opacity/discoloration
      visible without air drying) or V3 (enamel breakdown in opaque/discoloured enamel
      and/or greyish discoloration) were suitable cut-off points at the d3 threshold.
      CONCLUSION: Visual examination was more accurate than bitewing radiographs for
      detection at the d1 threshold (the cut-off point of V1). Either V2 or V3 can be
      used for caries detection at the d3 threshold.

PMID- 17559455
TI  - The use of micro-Raman spectroscopy to differentiate between sound and eroded
      primary enamel.
AB  - OBJECTIVE: The aim of this study was to investigate differences in phosphate
      group concentration between areas of sound and eroded enamel in primary teeth
      using micro-Raman spectroscopy (MRS). METHODS: The Raman spectroscopic technique
      enables researchers to obtain information about molecules by analysing scattered
      light caused by monochromatic laser excitation. Ten extracted anterior primary
      teeth with areas of sound and eroded enamel were used. Three, 10-s scans were
      carried out at three points along a 3-microm linear area in both sound and eroded
      primary enamel, and Raman spectra were obtained with the LabRam 300 fitted with
      an Olympus BX40 microscope. Scanning electron microscopy was used to confirm the
      presence of sound and eroded enamel on each tooth. RESULTS: The phosphate nu(1)
      band was located between 958.5 and 967.0 cm(-1). There was no statistically
      significant difference between the area under the phosphate nu(1) band values for
      the eroded and sound areas (P = 0.7302). Scanning electron microscopy confirmed
      the presence of sound and eroded areas on all specimens. CONCLUSION: In this
      study, there was no statistically significant difference found between phosphate
      group concentration in eroded and sound primary enamel when analysed by MRS.

PMID- 17559456
TI  - Reliability and validity of a faces version of the Modified Child Dental Anxiety
      Scale.
AB  - BACKGROUND: A new version of the Modified Child Dental Anxiety Scale (MCDAS) was
      formed by adding a faces rating scale to the original numeric form. AIMS: To
      describe the psychometric properties of the faces version of the Modified Child
      Dental Anxiety Scale (MCDAS(f)), and to provide normative data for dental anxiety
      for children using the MCDAS(f). DESIGN: To determine the test-retest
      reliability, 287 schoolchildren aged 8-10 years completed the MCDAS(f) on two
      separate occasions 17 weeks apart. To determine the criterion validity, 207
      schoolchildren aged 10-12 years completed the MCDAS(f) and the CFSS-DS at the
      same sitting. Construct validity was assessed using a cohort of 206 consecutive
      child dental patients and their parents. RESULTS: The MCDAS(f) showed good test
      retest reliability (intraclass correlation coefficient = 0.80) and internal
      consistency (Cronbach's alpha = 0.82). The MCDAS(f) significantly correlated with
      the CFSS-DS (r = 0.80, P < 0.001). Dental anxiety assessed using the MCDAS(f) was
      related to the dmft (t = -2.17, P = 0.03), DMFT (t = -4.19, P < 0.001), and
      dental general anaesthetic experience (t = -4.46, P < 0.01). The mean MCDAS(f)
      score for the normative sample (n = 475) was 19.81 (95% CI: 19.20, 20.43).
      CONCLUSIONS: The MCDAS(f) is a reliable and valid measure of dental anxiety in
      children aged 8-12 years.

PMID- 17559457
TI  - Dental caries in 0- to 5-year-old Brazilian children: prevalence, severity, and
      associated factors.
AB  - OBJECTIVE: This cross-sectional study investigated the prevalence and severity of
      dental caries and their association with demographic and socio-economic variables
      in Brazilian preschoolers. METHODS: The study population comprised 1487 0- to 5
      year-old children attending government nurseries in Canoas, southern Brazil.
      Questionnaires regarding information related to the independent variables (age,
      gender, maternal level of education, and family income) were completed by the
      parents. Clinical examinations were carried out by five trained examiners and
      results were expressed using the deft index (World Health Organization criteria),
      including white spots. The outcomes considered in this study were caries
      occurrence (deft > 0) and caries severity (deft). RESULTS: Forty per cent of the
      children (589/1487) presented dental caries [mean deft (SD): 1.53 (2.75)]. Deft
      increased with age (P < 0.001) and was significantly higher in children from
      mothers with low educational level (P = 0.001) and low family income (P = 0.001).
      The greatest increase in caries prevalence and severity occurred between age
      groups of 1 and 2 years. Logistic regression demonstrated higher odds of dental
      caries with mother's completing < 4 years education, after adjusting for
      confounding. CONCLUSION: These findings indicate the need for preventive
      programmes, which should begin in the first year of life, with special attention
      given to families with mothers presenting low education levels.

PMID- 17559458
TI  - Randomized controlled trial of the intraligamental use of a local anaesthetic
      (lignocaine 2%) versus controls in paediatric tooth extraction.
AB  - BACKGROUND: Children still experience pain upon waking following dental
      extraction under general anaesthesia. Local anaesthetic has been shown to reduce
      this pain, but needs to be administered via a method that causes minimum injury
      or distress to the child. AIM: This study aims to evaluate the use of
      intraligamental injection of local anaesthetic, under general anaesthesia prior
      to the extraction of the tooth, for postoperative pain control in children aged 2
      5 years. DESIGN: A randomized, single-blind, controlled trial of intraligamental
      lignocaine (2% lignocaine solution with adrenaline (epinephrine) 1 : 80 000) for
      primary teeth extraction under general anaesthesia was performed. Pain was scored
      by the investigators at 5-, 15-, 30-, and 60-min time points in the first hour
      using the Toddler-Preschooler Postoperative Pain Scale. RESULTS: Eighty-six
      children were recruited in the study: 42 randomized in the lignocaine treatment
      group and 44 in the control group. There was no significant difference (P = 0.42,
      Mann-Whitney U-test) in the cumulative four time point median pain score over the
      first hour. In the lignocaine treatment group, this was 3 (interquantile range
      (IQR) 0-7.5) and in the control group this was 3 (IQR: 0-10). At the 5-min time
      point after the child returned from recovery, the pain score in the lignocaine
      group (0 IQR 0-1) was statistically lower than that in the control group (0 IQR 0
      5) (P = 0.023). There was no difference in the 15-, 30-, or 60-min time points.
      CONCLUSIONS: Intraligamental lignocaine used for dental extraction under general
      anaesthesia in young children initially causes less pain after recovery, but this
      difference is not sustained over the first hour after dental extraction.

PMID- 17559459
TI  - Multiple supernumerary teeth in the maxillary canine and mandibular premolar
      regions: a case in the postpermanent dentition.
AB  - BACKGROUND: A supernumerary tooth is an extra tooth above the normal number, of
      which approximately 90% occur in the premaxillary region and show rudimentary
      forms of crown morphology. Most cases occur singly, with bilateral occurrence in
      the maxillary canine regions very rare in children with no other associated
      diseases or syndromes. CASE REPORT: A case of a 14-year-old boy with bilateral
      supernumerary teeth with normal crown shapes in both the maxillary canine and
      mandibular premolar regions. The supernumerary teeth in the maxilla were
      diagnosed at 12.2 years of age and in the mandible at 14.1 years of age.
      CONCLUSION: Four supernumerary teeth in the maxillary and mandibular canine
      premolar region is a rare finding.

PMID- 17559460
TI  - Complete spontaneous regression of congenital epulis in a baby by 8 months of
      age.
AB  - BACKGROUND: This paper describes the case of a 7-day-old girl who was referred to
      a paediatric dentistry clinic because of the presence of a pedunculated mass
      protruding from the front of her mouth. CASE REPORT: The mass was attached to the
      maxillary alveolus to the right of the midline, and was clinically diagnosed as a
      congenital epulis. The baby had no airway obstruction and was able to feed well.
      A conservative treatment was proposed, with monthly follow-up appointments to
      monitor the lesion. CONCLUSION: After 8 months, the lesion had completely
      regressed, meaning that the girl did not have to be exposed to unnecessary
      surgical procedures in her first few days of life. The eruption of the upper
      anterior teeth was not affected.

PMID- 17559463
TI  - Stroma remodelling during healing of corneal surface irregularities induced by
      PTK.
AB  - PURPOSE: To study the histopathology of the remodelling process in the stroma
      after excimer-laser-induced corneal irregular injuries. METHODS: Seven New
      Zealand white rabbits received in one eye a transepithelial plano photoablation
      (60 microm) and an additional plano ablation (25 microm). On the denuded stroma,
      an electron microscopy specimen grid was placed and another 25 microm ablation
      was applied to produce surface irregularities. Dichlorotriazinyl aminofluorescein
      (DTAF) was then applied for 45 seconds. Another seven right eyes of seven rabbits
      were ablated the same way but without using the grid, resulting in a plano
      ablation. All the rabbits were killed at weekly intervals after treatment. The
      harvested corneas from both eyes were further processed for haematoxylin-eosin
      staining and were also stained with monoclonal antibodies directed against Ki-67
      antigen and alpha-smooth muscle actin (alpha-SMA). All specimens were examined
      under light and fluorescence microscope. RESULTS: The corneal wounds were covered
      by epithelium during the first week. The 25 microm x 25 microm x 25 microm
      stromal irregularities were clearly discernible up to 3 weeks after treatment,
      during which time they melted and disappeared. A homogeneous zone was formed in
      which stroma cells laid down an initially disorganized stroma. This was sharply
      visible under a fluorescence microscope as a dark area between the
      dichlorotriazinyl aminofluorescein (DTAF) fluorescent stroma and autofluorescent
      epithelium. Very little response was seen in the plano-ablated wound
      microscopically and in terms of positive stained cells. CONCLUSION: As the
      irregularities are flattened and the homogenous zone becomes repopulated with
      keratocytes forming extracellular matrix material (ECM), the cornea regains its
      previous architecture in both groups. The irregular wound surface promotes wound
      healing reactivity, a process that allows the cornea to compensate for the
      irregularities and heal to a functional state.

PMID- 17559462
TI  - Regeneration of the epithelium in organ-cultured donor corneas with extended post
      mortem time.
AB  - PURPOSE: The maximum post-mortem time limit for obtaining donor corneas varies
      between eye banks. It is not known for how long a time the epithelial cells
      survive post-mortem, nor is it known if donor corneas with extended post-mortem
      time are able to regenerate the epithelium. Therefore, we wanted to examine the
      epithelium in donor corneas for regenerative ability during storage in an eye
      bank organ culture system. METHODS: Twenty-four paired donor corneas with post
      mortem time from 28 to 163 hr were obtained. One cornea of a pair was fixed
      immediately to serve as a control, and the second was cultured in eye bank medium
      at 32 degrees C for 3 days. Examination of the specimens was performed with light
      and scanning electron microscopy. Immunohistochemical staining methods with
      antibodies against K 3, K 19, vimentin and p63 were used to further characterize
      the cells. RESULTS: The control corneas showed decreasing amounts of epithelial
      cells with increasing post-mortem time. All the cultured corneas demonstrated
      rapid regeneration of the epithelium. After 3 days in organ culture, 10 of 12
      donor corneas were covered with epithelium. CONCLUSION: Even up to 7 days post
      mortem, viable cells reside in the corneal epithelium. The study demonstrates the
      hardiness and enormous regenerative potential of peripheral corneal cells. Donor
      corneas processed in an eye bank organ culture storage system will obtain an
      intact epithelial layer within a few days.

PMID- 17559464
TI  - Expression of the focal adhesion protein PINCH in normal and alkali-injured
      corneas and the role of PMNs.
AB  - PURPOSE: To evaluate the role of particularly interesting new cysteine-histidine
      rich protein (PINCH) in corneal wound healing and early neovascularization and to
      assess the influence of granulocytes. METHODS: A standardized corneal alkali
      wound was inflicted under general anaesthesia to the right eye of 14 New Zealand
      White rabbits. Seven of the rabbits received i.v. 5 mg/kg fucoidin every 2 hours
      to prevent granulocytes from entering the wound area. After 36 hours, the rabbits
      were killed, the corneas excised, fixed in 4% formaldehyde and embedded in
      paraffin. The sections were double-stained with antibodies against PINCH and with
      haematoxylin. RESULTS: In the normal cornea and limbus, PINCH was weakly
      expressed in the corneal epithelium and in a wedge of the conjunctival stroma. In
      the wounded corneas, PINCH expression was seen in the frontline of repopulating
      endothelial and epithelial cells, and in active keratocytes. The vascular
      endothelium and the granulocytes expressed PINCH, as did the conjunctival
      epithelium. In the fucoidin-treated rabbits, PINCH expression was markedly
      reduced. The vascular endothelial cells and the few granulocytes did not express
      PINCH in these rabbits. CONCLUSIONS: PINCH is only slightly expressed in the
      normal cornea. A corneal wound induces PINCH expression in the repopulating
      cells, in the vascular endothelial cells of the limbus, in the limbal epithelium
      and in the granulocytes. Exclusion of granulocytes reduces expression of PINCH
      and there is no expression at all in the vascular endothelium.

PMID- 17559465
TI  - Corneal flap thickness with the Moria M2 single-use head 90 microkeratome.
AB  - PURPOSE: To analyse the accuracy of corneal flap thickness created in laser
      assisted in situ keratomileusis (LASIK) using the Moria Model 2 (M2) single-use
      head 90 microkeratome. METHODS: The corneal thickness of 300 (266 myopic and 34
      hyperopic) eyes of 150 patients was measured by ultrasonic pachymetry
      preoperationally and intraoperationally after flap cut. The Moria M2 single-use
      head 90, intended to create a flap with a thickness of 120 microm, was used in
      all eyes. The right eye was always operated first and the left eye second, using
      the same blade. RESULTS: Mean corneal flap thickness was 115.4 microm (standard
      deviation [SD] 12.5) in the two eyes, 115.7 microm (SD 12.4, range 73-147 microm)
      in right eyes and 115.1 microm (SD 12.6, range 74-144 microm) in left eyes. Mean
      horizontal flap diameter was 9.1 mm (SD 0.2) and mean hinge length 4.1 mm (SD
      0.1). There were no free flaps, incomplete flaps or flaps with buttonholes in the
      study. Occasional iron particles were observed in three (1.0%) eyes. CONCLUSIONS:
      As with most microkeratomes, the single-use head 90 microkeratome cut thinner
      flaps than were intended. The range of the cuts was relatively wide. However,
      thin flaps did not increase the rate of flap-related complications. The
      difference between the first and second eyes was not significant.

PMID- 17559466
TI  - Corneal endothelial cell density reduction: a complication of retinal
      photocoagulation with an indirect ophthalmoscopy contact lens.
AB  - PURPOSE: To investigate the influence of retinal photocoagulation with an
      indirect ophthalmoscopy contact lens on corneal endothelial cells. METHODS:
      Seventeen eyes of 17 patients were evaluated, and corneal endothelial cells were
      measured twice: just before retinal photocoagulation using an indirect
      ophthalmoscopy contact lens and 33.2 +/- 10.2 days after surgery. RESULTS: A
      statistically significant reduction was found in corneal endothelial cell numbers
      before versus after surgery (P = 0.0003). CONCLUSION: Our results show corneal
      endothelial cells to be decreased by retinal photocoagulation with an indirect
      ophthalmoscopy contact lens. When a patient with a low corneal endothelial cell
      density receives retinal photocoagulation using an indirect contact lens, it is
      important to be aware of the potential for further loss.

PMID- 17559467
TI  - Results of vision screening of 6-year-olds at school: a population-based study
      with emphasis on screening limits.
AB  - PURPOSE: To evaluate newly introduced vision screening of 6-year-olds in the
      preschool class with special regard to screening criteria. METHODS: Monocular
      visual acuity (VA) testing in 6-year-olds by school nurses as part of preventive
      health care was introduced in Sweden 2003. Children with VA < 0.8 (logMAR 0.1) or
      symptoms are referred to eye clinics where VA testing, cover testing, cycloplegic
      autorefraction and ophthalmoscopy are performed. The present screening limit of
      0.8 (logMAR 0.1) was evaluated in relation to a limit of 0.65 (logMAR 0.2). All
      children in the City of Gothenburg starting preschool class in 2003 were
      included. RESULTS: A total of 127 schools with 3885 pupils participated. Of
      these, 255 pupils (6.6%) were referred and 236 underwent an ophthalmological
      examination. Children with a VA of 0.65 (logMAR 0.2) in the worse eye constituted
      74.5% of those who had failed the screening; more than half of these were found
      to have VA > or = 0.8 (logMAR 0.1) in the clinic. Many were not refracted in
      cycloplegia and only 6.7% were found to have significant ametropia. The criteria
      for the prescription of glasses varied; 13.4% of these children were prescribed
      glasses for insignificant refractive errors. CONCLUSIONS: Six-year-olds with VA
      of 0.65 (logMAR 0.2) rarely have defects that require treatment and the screening
      criterion of 0.8 (logMAR 0.1) is probably too demanding for effective utilization
      of available resources. Retest before referral and refraction in cycloplegia of
      all children with reduced VA or visual symptoms are recommended.

PMID- 17559468
TI  - Eye muscle force development in thyroid-associated ophthalmopathy in different
      stages of disease.
AB  - PURPOSE: Ocular motility disturbances are common in patients with thyroid
      associated ophthalmopathy (TAO). A quantitative evaluation of the isometric force
      of the eye muscles in TAO might be useful in the detection of early stages of
      this disease. METHODS: A total of 32 patients with TAO were divided into three
      groups according to whether they had mild active, pronounced, active, or
      longstanding, inactive disease. A group of six patients with Graves' disease
      without clinical signs of TAO and a group of 10 control subjects were also
      studied. The development of isometric force during saccadic eye movements of 5-,
      10- and 20-degree amplitude in horizontal and vertical directions of gaze were
      recorded in the more affected eye in patients and the non-dominant eye in normal
      subjects, using a suction contact lens/strain gauge technique. RESULTS: Peak
      tension (Fp) in vertical and horizontal saccadic movements was not significantly
      different between groups. Steady-state tension (Fs) was significantly higher in
      the groups with pronounced, active and longstanding, inactive disease than in the
      other groups for vertical (p < 0.01) and horizontal movements (p < 0.05).
      Abnormal force development in any of the gaze directions was seen in all patients
      with pronounced, active and longstanding, inactive TAO, and in some of the
      patients with mild, active TAO and Graves' disease without TAO. CONCLUSIONS:
      Increased eye muscle tension was recorded in different gaze directions,
      confirming multiple extraocular muscle involvement in TAO. It is suggested that
      the increased force development reflected contractile compensations for
      restrictions of ocular motility due to higher muscle stiffness in thyroid
      associated eye muscle disease. Tension measurements can be used to identify
      muscle involvement in TAO.

PMID- 17559469
TI  - The multifocal electroretinogram (mfERG) in the pig.
AB  - PURPOSE: To establish a method allowing multifocal electroretinography (mfERG)
      recording with simultaneous fundus monitoring on anaesthetized pigs. In addition
      we characterize the peaks of the porcine mfERG trace, and compare the visual
      streak area with the optic nerve head, a known non-response area. Finally we
      illustrate the feasibility of the method by performing mfERG after an induced
      laser burn in the visual streak. METHODS: Fifteen pigs underwent mfERG recordings
      at baseline, and after 1 and 6 weeks of observation. One pig was evaluated before
      and after retinal diode laser treatment in the visual streak. RESULTS: The
      porcine mfERG trace appears similar to the human mfERG trace, and can be
      described by three peaks named N1, P1 and N2. Significantly faster implicit time
      was found in the visual streak regarding N1 (P < 0.001) than in areas outside the
      visual streak. Amplitudes of all three peaks were increased in the visual streak
      (P < 0.005). The laser-treated area was characterized by a response similar to
      what is found at the location of the optic nerve head. CONCLUSION: Porcine mfERG
      is similar in appearance to the human response and can be described by the same
      three peaks. Significantly higher amplitudes of all three peaks are found in the
      visual streak when compared to the optic nerve head and inferior retina. We have
      detected the functional deficit caused by a laser burn at the size of 3 x 3 mm.

PMID- 17559470
TI  - Sequels of Purtscher's retinopathy imaged by enhanced optical coherence
      tomography.
AB  - PURPOSE: To report the optical coherence tomography (OCT) findings in a case of
      Purtscher's retinopathy. METHODS: Enhanced optical coherence tomography, fundus
      photography, multifocal electroretinography. RESULTS: A 27-years-old female
      parachutist demonstrated outer retinal opacification with small intraretinal
      hemorrhages and corresponding binocular pericentric ring scotomata one day after
      suffering an unusually abrupt arrest of a free fall upon the unfolding of her
      parachute. When seen 20 years later, the scotomata were unchanged and optical
      coherence tomography showed bilateral disorganization at the transition between
      the retinal photoreceptor outer segments and the retinal pigment epithelium plus
      attenuation of the outer nuclear layer. CONCLUSIONS: Our observations document
      that the long term sequels of Purtscher's retinopathy are located in the outer
      segments of the photoreceptors.

PMID- 17559471
TI  - Optical coherence tomography of astrocytic hamartomas in tuberous sclerosis.

PMID- 17559472
TI  - Intraoperative dehiscence of laser subepithelial keratomileusis (LASEK) flap
      during retinal detachment surgery.

PMID- 17559473
TI  - Intraocular plastic foreign bodies, introduced via the Monarch II intraocular
      lens delivery system.

PMID- 17559474
TI  - Giant cell arteritis with normal inflammatory markers.

PMID- 17559477
TI  - Interview with David Niv, MD, FIPP. Interview by P. Prithvi Raj.

PMID- 17559478
TI  - Identifying exaggeration and malingering.

PMID- 17559479
TI  - Attitudes and beliefs regarding the role of interventional pain management at the
      end-of-life among caregivers: a 4-year perspective.
AB  - Intrathecal and epidural opioid analgesia represents a major advance in the
      management of cancer pain, adding a new dimension to opioid therapy by allowing
      prolonged analgesia through the use of significantly lower doses than those
      required for systemic administration. However, myths, misconceptions, and
      apprehension continue to serve as major barriers to effective cancer pain
      management, and concerns regarding safety, efficacy, and relative ease of
      utilization still prevail. This, in turn, results in unnecessary suffering,
      depression, diminished cognitive function, sleep disturbance, functional
      disability, and compromised quality of life. We conducted a survey to
      systematically explore medical and paramedical attitudes prior to and 4 years
      after the introduction an interventional pain program and attempted to
      qualitatively analyze what appeared as main facilities or difficulties following
      end-of-life clinical experiences. In general we found that all caregivers were
      satisfied from using interventional pain relief techniques at the end-of-life;
      more so among caregivers directly involved in patient care. Although nearly half
      of the responders initially found "technical manipulations" moderately difficult
      to difficult, after a simple hands-on instruction all found these techniques to
      be "helpful, simple and feasible." "When all went well," caregivers found
      implantable devices as a useful tool to relieve pain, to increase the ability of
      patients to complete personal endeavors, notably mobilization, but also noted an
      increased patient anxiety at the end-of-life. "When all went wrong," caregivers
      evoked the paradoxical attitude of patients to having a "high-tech" treatment at
      the end-of-life, causing them eventually to have "false hope," as well as the
      phenomenon of "interdisciplinary hyperactivity," creating what was referred to as
      therapeutic futility. In summary, this study suggests the importance on insisting
      to introduce novel techniques into practice despite initial apprehension,
      however, quality improvement by detecting and overcoming attitudinal barriers
      remain primordial and requires narrative research.

PMID- 17559480
TI  - Presurgical Behavioral Medicine Evaluation (PBME) for implantable devices for
      pain management: a 1-year prospective study.
AB  - To reduce poor surgical outcomes, presurgical psychological evaluations are used
      to better predict prognosis. The current study investigated the utility of a
      revised Presurgical Behavioral Medicine Evaluation (PBME) algorithm, developed
      specifically for patients who were candidates for implantable devices. Patients
      were categorized into a Green, Yellow I, Yellow II, or Red prognosis group, with
      Green having the best, and Red having the worst, prognosis for good surgical
      outcomes. Variables, including gender, disability payment status, and involvement
      in pending litigation, were found to be significantly different among the groups
      in a sample of 95 consecutive patients. Analysis of data at the initial
      evaluation indicated that patients within the Red group endorsed significantly
      more physical/functional limitations, depressive symptomatology, and psychosocial
      distress than the Green group. In a 12-month follow-up analysis, significant
      differences among the four groups on various psychosocial measures were found. In
      addition, post-hoc tests revealed specific significant differences among the
      groups. A repeated measures analysis of the initial evaluation, 6-month, and 12
      month follow-up data revealed that these measures were also significantly
      affected by the prognostic group. Lastly, nonparametric analysis indicated that
      there were significant differences among the groups on total risk factor scores
      as determined by the PBME algorithm.

PMID- 17559481
TI  - Opioid rotation from high-dose morphine to transdermal buprenorphine (Transtec)
      in chronic pain patients.
AB  - Opioid rotation is increasingly becoming an option to improve pain management
      especially in long-term treatment. Because of insufficient analgesia and
      intolerable side effects, a total of 42 patients (23 male, 19 female; mean age
      64.1 years) suffering from severe musculoskeletal (64%), cancer (21%) or
      neuropathic (19%) pain were converted from high-dose morphine (120 to >240
      mg/day) to transdermal buprenorphine. The dose of buprenorphine necessary for
      conversion (at least 52.5 microg/h) was titrated individually by the treating
      physician. No conversion recommendations were given and the treating physician
      used his or her own judgment for dose adjustment. Pain relief, overall
      satisfaction and quality of sleep (very good, good, satisfactory, poor, or very
      poor), and the incidence and severity of adverse drug reactions over a period of
      at least 10 weeks and up to 1 year was assessed. Following rotation, patients
      experiencing good/very good pain relief increased from 5% to 76% (P < 0.001).
      Only 5% reported insufficient relief. Relief was achieved with buprenorphine
      alone in 77.4%, while 17% needed an additional opioid for breakthrough pain.
      Sleep quality (good/very good) increased from 14% to 74% (P < 0.005). Adverse
      effects were reported in 11.9%, mostly because of local irritation, did not
      result in termination of therapy. Neither tolerance nor refractory effect
      following rotation from morphine to buprenorphine was noted. Conversion tables
      with a fixed conversion ratio are of limited value in patients treated with high
      dose morphine.

PMID- 17559482
TI  - Novel intradiscal biacuplasty (IDB) for the treatment of lumbar discogenic pain.
AB  - Reported here is the treatment of severe axial discogenic pain in a young man
      utilizing the new minimally invasive transdiscal radiofrequency technique called
      intradiscal biacuplasty (Baylis Medical Inc., Montreal, Canada). The new
      procedure is detailed and step-by-step fluoroscopic imaging presented. There were
      no intra- and postoperative complications, and significant improvements in
      patient functional capacity, and pain scores were noted. Visual analog scale pain
      score decreased from 5 to 1 cm at 6-month follow-up, Oswestry disability scores
      improved from 14 (28% or moderate disability) to 6 points (12% or minimal
      disability) and SF-36-PF (physical function) score changed from 67 to 82.
      Potential advantages of cooled, bipolar radiofrequency to heat the posterior
      annulus are discussed.

PMID- 17559483
TI  - The beneficial effect of spinal cord stimulation in a patient with severe
      cerebral ischemia and upper extremity ischemic pain.
AB  - Spinal cord stimulation (SCS) is used in the treatment of chronic pain, ischemia
      because of obstructive arterial disease, and anginal pain. Recently, a number of
      studies have described the effects of the high cervical SCS, including increased
      cerebral blood flow, although the underlying mechanisms are unknown. This case
      report describes a patient with a severe complex ischemic condition affecting
      both cerebral and upper limb blood flow with an associated complex regional pain
      syndrome in upper limb. While all previous clinical treatments proved
      ineffective, cervical SCS afforded satisfactory results. Possible mechanisms
      underlying the cervical SCS effect are discussed.

PMID- 17559484
TI  - Treatment of refractory ischemic pain from chemotherapy-induced Raynaud's
      syndrome with spinal cord stimulation.
AB  - We report the successful treatment of refractory ischemic pain from cisplatin
      induced Raynaud's syndrome with spinal cord stimulation after failed
      pharmacologic management and surgical sympathectomy. CASE REPORT: A 48-year-old
      man developed ischemic pain of the hands while undergoing cisplatin and
      gemcitabine chemotherapy for metastatic pancreatic carcinoma. After extensive
      pharmacologic management and surgical sympathectomy failed to provide adequate
      analgesia, the patient underwent a percutaneous spinal cord stimulation trial
      followed by permanent implantation and received significant pain relief prior to
      succumbing to his illness. Spinal cord stimulation provided effective therapy for
      refractory ischemic pain, even after failed sympathectomy.

PMID- 17559485
TI  - Complete recovery from intractable complex regional pain syndrome, CRPS-type I,
      following anesthetic ketamine and midazolam.
AB  - OBJECTIVE: To describe the treatment of an intractable complex regional pain
      syndrome I (CRPS-I) patient with anesthetic doses of ketamine supplemented with
      midazolam. METHODS: A patient presented with a rapidly progressing contiguous
      spread of CRPS from a severe ligamentous wrist injury. Standard pharmacological
      and interventional therapy successively failed to halt the spread of CRPS from
      the wrist to the entire right arm. Her pain was unmanageable with all standard
      therapy. As a last treatment option, the patient was transferred to the intensive
      care unit and treated on a compassionate care basis with anesthetic doses of
      ketamine in gradually increasing (3-5 mg/kg/h) doses in conjunction with
      midazolam over a period of 5 days. RESULTS: On the second day of the ketamine and
      midazolam infusion, edema, and discoloration began to resolve and increased
      spontaneous movement was noted. On day 6, symptoms completely resolved and
      infusions were tapered. The patient emerged from anesthesia completely free of
      pain and associated CRPS signs and symptoms. The patient has maintained this
      complete remission from CRPS for 8 years now. CONCLUSIONS: In a patient with
      severe spreading and refractory CRPS, a complete and long-term remission from
      CRPS has been obtained utilizing ketamine and midazolam in anesthetic doses. This
      intensive care procedure has very serious risks but no severe complications
      occurred. The psychiatric side effects of ketamine were successfully managed with
      the concomitant use of midazolam and resolved within 1 month of treatment. This
      case report illustrates the effectiveness and safety of high-dose ketamine in a
      patient with generalized, refractory CRPS.

PMID- 17559486
TI  - Burning mouth syndrome: will better understanding yield better management?
AB  - "Burning mouth syndrome" (BMS) refers to a chronic orofacial pain disorder
      usually unaccompanied by mucosal lesions or other clinical signs of organic
      disease. BMS is typically characterized by a continuous, spontaneous, and often
      intense burning sensation as if the mouth or tongue were scalded or on fire.
      Burning mouth syndrome is a relatively common condition. The estimated prevalence
      of BMS reported in recent studies ranges between 0.7 and 4.6% of the general
      population. About 1.3 million American adults, mostly women in the postmenopausal
      period, are afflicted with BMS. The etiology of this disorder is poorly
      understood even though new evidence for a possible neuropathic pathogenesis of
      idiopathic BMS is emerging. Burning mouth syndrome may present as an idiopathic
      condition (primary BMS type) distinct from the symptom of oral burning that can
      potentially arise from various local or systemic abnormalities (secondary BMS
      type), including nutritional deficiencies, hormonal changes associated with
      menopause, local oral infections, denture-related lesions, xerostomia,
      hypersensitivity reactions, medications, and systemic diseases including diabetes
      mellitus. In more than a third of patients, multiple, concurrent causes of BMS
      may be identified. It is important to note that the diagnosis of BMS should be
      established only after all other possible causes have been ruled out.
      Professional delay in diagnosing, referring, and appropriately managing of BMS
      patients occurs frequently. Treatment should be tailored to each patient and it
      is recommended to practice the treatment in a multidisciplinary facility. This
      article discusses our current understanding of the etiology and pathogenesis of
      BMS. The authors have tried to emphasize new pharmacological approaches to manage
      this challenging disorder.

PMID- 17559487
TI  - Management strategies for pain in breast carcinoma patients: current opinions and
      future perspectives.
AB  - Breast cancer is the most frequently encountered carcinoma in women worldwide.
      Pain is the most distressing symptom in patients with breast carcinoma and can
      occur at all stages of the disease due to the cancer per se as well as due to
      various diagnostic and treatment modalities. A proper pain assessment helps in
      identification of pain syndromes and guides in formulating analgesic strategies.
      Primary therapies of breast carcinoma like surgery, chemotherapy, and
      radiotherapy for bony metastases can cause substantial pain relief. However,
      multimodal analgesic approaches incorporating pharmacological, interventional as
      well as non-conventional techniques should be employed prior to, in conjunction
      with, and after primary therapies of breast cancer. The prevalence of chronic
      neuropathic pain following breast cancer surgery may exceed 50% by current
      estimates, and with the increase in life expectancy of these patients, providing
      adequate pain relief is of paramount importance to improve their quality of life.
      In this review, we discuss prevailing methods of evaluation and management of
      pain in patients of breast carcinoma and the new techniques that may become the
      mainstay of pain management protocols in future.

PMID- 17559488
TI  - Evaluating malingering in contested injury or illness.
AB  - An interdisciplinary task force of physicians and neuropsychologists with
      advanced training in impairment and disability assessment provided a review of
      the literature on malingering in chronic pain, medical disorders, and
      mental/cognitive disorders. Our review suggests that treating health care
      providers often do not consider malingering, even in cases of delayed recovery
      involving work injuries or other personal injuries, where there may be a
      significant incentive to feign or embellish symptoms or delay recovery. This
      report discusses the implications of this issue and offers recommendations to
      evaluating physicians and other health care professionals.

PMID- 17559490
TI  - Why not ketamine?

PMID- 17559492
TI  - Bisphosphonate-related osteonecrosis of the jaws: a comprehensive review.
AB  - BACKGROUND: Bisphosphonate-related osteonecrosis of the jaws (BRONJ) presents the
      clinician with significant management dilemmas. The purpose of this study was to
      distil information related to this disorder by comprehensively reviewing the
      literature. METHODS: The structure and function of bisphosphonates, and their
      role in the development of BRONJ will be discussed, as will the possible
      mechanisms through which this pathology develops. A review of cases presented in
      the literature will be undertaken, and suggestions offered as to the management
      of this pathology in terms of surgical and conservative approaches. RESULTS:
      Presentation of BRONJ is currently more common in patients taking intravenous
      forms of bisphosphonates, but there is a fear that the long-term cumulative
      effects of oral bisphosphonates may see BRONJ increasingly occurring in this
      patient group. CONCLUSIONS: Prevention is superior to treatment, and the
      establishment of meticulous oral hygiene and pre-emptive surgical treatment prior
      to commencement of bisphosphonate therapy is recommended.

PMID- 17559493
TI  - A possible CD1a Langerhans cell-mast cell interaction in chronic hyperplastic
      candidosis.
AB  - AIMS: T lymphocyte-antigen-presenting cell (APC) interaction plays a central role
      in T lymphocyte activation and APC maturation. We therefore studied the CD1a
      positive Langerhans cells with respect to receptor activator of nuclear factor
      kappa B ligand (RANKL)-positive cells in chronic hyperplastic candidosis (CHC).
      MATERIALS AND METHODS: Tissue sections of CHC were compared with leukoplakia and
      healthy oral mucosa using RANKL and CD1a monoclonal antibodies in an avidin
      biotin peroxidase complex protocol. Two different antigen-retrieval protocols,
      pepsin preincubation and Tris-EDTA heat treatment, were used. RESULTS: CD1a
      positive Langerhans cells were in healthy and leukoplakia epithelium found in the
      middle layer, but in CHC in all layers of the epithelium, at the basement
      membrane and as mononuclear round cells in the lamina propria. Use of pepsin
      digestion enabled studies of mast cells and their activation in the form of
      degranulation of RANKL. CONCLUSIONS: The numerical, morphological and
      topographical versatility of the CD1a-positive Langerhans cells in CHC can be
      clarified by dendritic cell (DC) recruitment into the epithelium. RANK-positive
      and RANKL-sensitive DCs have ample opportunity to interact with local T
      lymphocytes. Use of an optimized antigen-retrieval protocol enabled demonstration
      of an active engagement (degranulation) of mast cells, which represent a rapidly
      available source of soluble RANKL.

PMID- 17559494
TI  - Coexistence of Sjogren's syndrome and sarcoidosis: a report of five cases.
AB  - BACKGROUND: Sjogren's syndrome (SS) and sarcoidosis are diseases that can affect
      the salivary glands and result in the loss of salivary gland function. Most of
      the criteria used for the diagnosis of SS exclude sarcoidosis before establishing
      the diagnosis of SS. However, several reports have suggested the coexistence of
      both SS and sarcoidosis in the same patient. OBJECTIVE: The purpose of this study
      was to present five cases that support a true coexistence of sarcoidosis and SS.
      METHODS: Clinical and laboratory findings of patients with evidence of having
      both SS and sarcoidosis were reviewed. The diagnosis of SS was based on the
      European community criteria; the diagnosis of sarcoidosis was based on the
      presence of serological, radiographic and/or histopathologic findings that are
      consistent with sarcoidosis. RESULTS: All patients fulfilled the criteria for the
      diagnosis of both diseases. CONCLUSION: Our findings appear to support a true
      coexistence of sarcoidosis with SS. Therefore, it is reasonable to suggest
      removing the exclusion of sarcoidosis from the diagnostic criteria for SS.

PMID- 17559495
TI  - Prevalence of oral Candida species in leprosy patients from Cambodia and
      Thailand.
AB  - BACKGROUND: Leprosy is a chronic bacterial infection which may lead to
      significant orofacial morbidity. However, reports on the oral mycotic flora of
      leprosy patients are rare. The aim of the current study was to explore the oral
      yeast carriage in two groups of leprosy patients. METHODS: 40 Cambodian (seven
      men, 33 women) and 48 Thai (14 men, 34 women) leprosy patients from Leprosy
      Rehabilitation Centre Khien Kleang, Phnom Penh, Cambodia and McKean
      Rehabilitation Center, Chiangmai, Thailand were randomly selected and their
      demographic data and clinical history were recorded. Tongue and palatal swabs of
      each patient were collected using sterile Fungi-Quick swabs (Hain Diagnostika,
      Nehren, Germany) and they were cultured aerobically on Sabouraud's dextrose agar
      and CHROMAgar (CHROMagar, Paris, France). Yeast were identified by germ tube,
      chlamydospore production, and assimilation tests (API 20C AUX, Bio-Merieux, Marcy
      l'Etoile, France) and reconfirmed using APILAB Plus system (Bio-Merieux).
      RESULTS: Two groups (Cambodian and Thai) had median age of 35 and 64 years. They
      had been with leprosy for median durations of 17.7 and 38.9 years (P<0.05),
      respectively. Overall yeast carriage in two cohorts were 80% and 93.75%. Candida
      albicans had highest carriage rate in either group (65.6%, 44.4%). Candida krusei
      and C. glabrata existed as second-line colonizers after C. albicans. Candida
      glabrata carriage was significantly higher in Thai patients (P<0.05).
      Multispecies carriage was seen in three Cambodian (9.4%) and five Thai (11.5%)
      patients. CONCLUSIONS: This study indicates high oral yeast carriage in leprosy
      patients. Candida albicans remains predominant while C. krusei and C. glabrata
      are second-line oral colonizers. Co-inhabitation of multiple yeast species is
      also noted in these patients' oral mycotic flora.

PMID- 17559496
TI  - Evaluation of the sensation in patients with trigeminal post-herpetic neuralgia.
AB  - BACKGROUND: Post-herpetic neuralgia (PHN) is one complication after herpes zoster
      infection, which may affect the facial superficial sensitivity. METHODS: Eighteen
      patients with PHN were interviewed and evaluated according to a systematized
      sensitivity approach, including mechanical, thermal and pain. RESULTS: The pain
      location was V1 in 15 patients. All trigeminal branches from both facial sides
      were evaluated; we compared the affected with the opposite side. There was a
      significant difference at V1 with cold (P=0.038), vonFrey (P=0.008) and pinpricks
      (P=0.022); at V2, the statistical difference occurred with cold (P=0.034), heat
      (P=0.019) and pinpricks (P=0.037); at V3, differences occurred with cold
      (P=0.042) and heat (P=0.036). Only V1 and oral mucosa (V2-3) presented pain
      threshold differences between both sides (P=0.001, P=0.021). CONCLUSION: Age,
      predominance of trigeminal PHN in V1 and continuous burning pain was common and
      similar to literature. Sensation was hampered with evident deficits of all
      sensory modalities in the affected trigeminal areas, especially V1.

PMID- 17559497
TI  - An association between the MICA-A5.1 allele and an increased susceptibility to
      oral squamous cell carcinoma in Japanese patients.
AB  - BACKGROUND: Recently, a new polymorphic gene family called the major
      histocompatibility complex class I chain-related gene A (MICA) was discovered
      about 40 kb centromeric to HLA-B gene. The MICA protein, expressed on epithelial
      cells and many kinds of tumor cells, serves to regulate immune function. The MICA
      protein is thought to activate immune function on mucosal tissue by binding to
      NKG2D which is expressed on most natural killer cells, CD8 positive T cells, and
      gamma delta T cells. An association between MICA gene polymorphisms and the
      development of oral squamous cell carcinoma (OSCC) has also been reported.
      OBJECTIVE: This study was designed to test this association in Japanese patients
      with OSCC. METHODS: The (GCT)(n) polymorphisms of the MICA gene was investigated
      in 123 patients with OSCC and 188 normal controls using polymerase chain reaction
      amplification and denaturing polyacrylamide gel electrophoresis. RESULTS: Five
      alleles, namely A4, A5, A6, A9, and A5.1, were found in both groups. The
      phenotype frequency of the MICA-A5.1 allele was significantly higher in patients
      with OSCC when compared with normal controls (OR 1.707, 95% CI 0.76-3.45,
      P=0.042). Also, the microsatellite frequency of the MICA-A5.1 allele was
      significantly higher in patients with OSCC compared with normal controls (OR
      1.664, 95% CI 0.82-3.42, P=0.021). Lastly, the frequency of the MICA-A5.1 allele
      was significantly higher in those with lymph node metastasis from OSCC compared
      with normal controls (OR 2.605, 95% CI 1.14-5.27, P=0.026). CONCLUSIONS: These
      results suggest that the MICA-A5.1 allele may be associated with an increased
      susceptibility to OSCC in Japan.

PMID- 17559498
TI  - Analysis of histopathological and immunohistochemical differences of oral
      squamous cell carcinoma in young and old patients in Sri Lanka.
AB  - BACKGROUND: Oral squamous cell carcinoma (OSCC) most commonly occurs in the
      middle-aged and older individuals. The purpose of the present study was to
      evaluate the histopathological and immunohistochemical differences of the younger
      (<40 years) and the older (more than 50 years) groups. METHODS: The
      histopathological parameters of 112 patients (younger 56 and older 56) were
      compared according to three grading systems (Broder JAMA 1920; 74: 656, Anneroth
      et al. Scand J Dent Res 1987; 95: 229, Bryne et al. J Pathol 1992; 166: 375) and
      as individual histopathological parameters. Further, the expression of p53 and
      Proliferative Cell Nuclear Antigen (PCNA) index was also compared. RESULTS:
      Although there was no significant difference between two groups regarding the
      three grading systems, a significantly higher number of nuclear aberrations was
      found in younger group (P<0.001). Interestingly, higher number of mitoses
      (P<0.05) and lymph node metastasis (P<0.05) were observed in the older group
      (P<0.05). Furthermore, significantly a higher PCNA index was found in the older
      group (P<0.005). CONCLUSIONS: Although tumours of the young patients showed more
      nuclear aberrations, OSCC of the older patients is proliferative and showed
      higher metastatic rate.

PMID- 17559499
TI  - An orthotopic floor-of-mouth model for locoregional growth and spread of human
      squamous cell carcinoma.
AB  - The molecular investigation of head and neck cancer targets requires the
      utilization and optimization of established animal models to characterize the
      effects of gene transcription and protein expression on invasion and metastasis.
      Floor-of-the-mouth murine models have been developed to study tumor growth,
      invasion, and metastasis of murine squamous cell carcinoma (SCC) cells in
      immunocompetent mice and invasion and metastasis of human SCC cells in nude mice.
      However, there are tumor cell lines that do not produce tumors in mice, using
      standard techniques, thus reducing the utility of the model to study specific
      genetic or treatment conditions. Furthermore, these techniques require large
      tumor volumes raising the possibility of airway compromise. In this report, we
      detail significant modifications to the orthotopic floor-of-mouth murine model
      for human SCC to facilitate predictable growth of a large panel of University of
      Michigan SCC cell lines. Furthermore, we describe the use of bioluminescence and
      micro-computed tomography to monitor tumor growth and bony invasion.

PMID- 17559500
TI  - DNA ploidy analysis in salivary gland tumours by image cytometry.
AB  - AIM: To determine whether DNA ploidy by image cytometry is a good diagnostic tool
      to distinguish benign and malignant salivary gland tumours. METHODS: A total of
      62 salivary gland tumours were studied. Cases were histologically diagnosed
      [haematoxylin and eosin (H&E)]. According to the World Health Organization (WHO)
      classification, there were 14 mucoepidermoid carcinomas (MEC), 11 adenoid cystic
      carcinomas (ACC), 10 pleomorphic adenomas (PA), 10 carcinoma ex PA (CEPA), 9
      acinic cell carcinomas (ACCa), 3 polymorphous low-grade adenocarcinomas (PLGA), 2
      papillary cystadenocarcinomas (PC), 1 myoepithelial carcinoma (MC), 1
      undifferentiated carcinoma (UC) and 1 mucinous adenocarcinoma (MA). Paraffin
      sections (40 microm) were micro-dissected to isolate tumour areas; cell nuclei
      were extracted and Feulgen-stained cytospin monolayers were analysed using a DNA
      image cytometry system. For each case, DNA index (DI) was calculated relative to
      internal controls (lymphocytes; DI=1.0). Cases were categorized as diploid or
      aneuploid and the proportion of cells over 5c was also calculated. RESULTS: Fifty
      three of 62 salivary gland tumours were uniformly diploid. Only nine cases were
      aneuploid: five CEPA, one low-grade MEC, one PC, one UC and one MA. CONCLUSIONS:
      The vast majority of salivary gland tumours were diploid. High-grade malignancies
      may be aneuploid, and ploidy may be useful to identify malignant change in
      atypical PA. Further, larger studies are needed to confirm our results and to
      further evaluate the usefulness of the technique in high-grade lesions.

PMID- 17559501
TI  - Application of fluorescence microscopy on hematoxylin and eosin-stained sections
      of healthy and diseased teeth and supporting structures.
AB  - Destruction of dental tissue and supporting structures is usually microscopically
      assessed by routine hematoxylin and eosin (HE)-stained sections. This short
      communication is concerned with the potential role of fluorescence microscopy of
      HE-stained sections to study morphological aspects of intact and pathological
      teeth in dental research. This methodology improves the visualization of the
      anatomical structures of the intact teeth, especially anatomical features and
      periodontal ligament spatial distribution. This technique also improves the
      visualization of the root and bone resorption and the delineation of the
      periapical lesion extension. The fluorescence microscopy technique of HE-stained
      sections is an easy, reliable and inexpensive method that seems to be a useful
      tool for evaluating morphological aspects of intact and pathological teeth in
      dental research.

PMID- 17559502
TI  - Cellular senescence in human myoblasts is overcome by human telomerase reverse
      transcriptase and cyclin-dependent kinase 4: consequences in aging muscle and
      therapeutic strategies for muscular dystrophies.
AB  - Cultured human myoblasts fail to immortalize following the introduction of
      telomerase. The availability of an immortalization protocol for normal human
      myoblasts would allow one to isolate cellular models from various neuromuscular
      diseases, thus opening the possibility to develop and test novel therapeutic
      strategies. The parameters limiting the efficacy of myoblast transfer therapy
      (MTT) could be assessed in such models. Finally, the presence of an unlimited
      number of cell divisions, and thus the ability to clone cells after experimental
      manipulations, reduces the risks of insertional mutagenesis by many orders of
      magnitude. This opportunity for genetic modification provides an approach for
      creating a universal donor that has been altered to be more therapeutically
      useful than its normal counterpart. It can be engineered to function under
      conditions of chronic damage (which are very different than the massive
      regeneration conditions that recapitulate normal development), and to overcome
      the biological problems such as cell death and failure to proliferate and migrate
      that limit current MTT strategies. We describe here the production and
      characterization of a human myogenic cell line, LHCN-M2, that has overcome
      replicative aging due to the expression of telomerase and cyclin-dependent kinase
      4. We demonstrate that it functions as well as young myoblasts in xenotransplant
      experiments in immunocompromized mice under conditions of regeneration following
      muscle damage.

PMID- 17559503
TI  - Serotonin receptors antagonistically modulate Caenorhabditis elegans longevity.
AB  - The neurotransmitter serotonin has been implicated in affecting the variation of
      longevity in natural Drosophila populations and age-related diseases in mammals.
      Based on these observations, it has been predicted that serotonin signal, perhaps
      at levels of serotonin biosynthesis, may control lifespan. Here, we investigated
      a variety of mutations in serotonin-signal genes, including serotonin
      biosynthesis genes, a serotonin transporter gene, and serotonin receptor genes.
      Despite this prediction, mutations in the serotonin biosynthesis genes had little
      or modest effects on lifespan, while the mod-5 mutation with increased
      availability of serotonin caused a modest life-shortening effect. In contrast, a
      deletion mutation of the ser-1 serotonin receptor gene increased longevity by up
      to 46%, likely through the insulin/insulin-like growth factor 1 pathway. This
      result suggests an interaction between the serotonin pathway and the
      insulin/insulin-like growth factor 1 pathway. A deletion mutation of another
      serotonin receptor gene, ser-4, shortened early to mid lifespan. The results
      suggest that serotonin signal antagonistically modulates longevity through
      different serotonin receptors. This study may indicate serotonin receptors as a
      potential target for antigeric interventions.

PMID- 17559504
TI  - The role of two LEAFY paralogs from Idahoa scapigera (Brassicaceae) in the
      evolution of a derived plant architecture.
AB  - Idahoa scapigera produces solitary flowers in the axils of rosette leaves without
      elongation of the shoot axis, a rosette-flowering architecture. Previous work
      with one of the two I. scapigera LFY paralogs, IscLFY1, showed that this gene
      caused aerial flowering rosettes in Arabidopsis thaliana. In this paper, we
      report that after three generations IscLFY1 transgenic lines are phenotypically
      indistinguishable from wild-type Arabidopsis, indicating that IscLFY1 protein is
      able to replace normal LFY function. Additionally, we found that ectopic LFY
      expression late in development can phenocopy aspects of the aerial rosette
      phenotype, suggesting that shoot compression caused by IscLFY1 could be caused by
      localized overexpression of a functional IscLFY protein. We also characterized
      the expression and function of the second I. scapigera LFY paralog, IscLFY2, in
      A. thaliana. In contrast to IscLFY1, this paralog was expressed in floral
      meristems and the shoot apical meristem (SAM). In I. scapigera, LFY-specific
      antibodies detected high protein levels in developing flowers but not in the
      apex, suggesting trans-regulatory differences between I. scapigera and A.
      thaliana. Most IscLFY2 transgenic A. thaliana plants were indistinguishable from
      wild type, but in a minority of lines the SAM was converted to a terminal flower
      as would be expected from the reporter-expression pattern. Taken together these
      results show that both I. scapigera paralogs have conserved LFY function, both
      proteins can rescue lfy and both can modify inflorescence architecture in an A.
      thaliana background: either by affecting internode elongation (IscLFY1) or by
      causing homeotic conversion of shoots into flowers (IscLFY2).

PMID- 17559505
TI  - An Arabidopsis MLH1 mutant exhibits reproductive defects and reveals a dual role
      for this gene in mitotic recombination.
AB  - The eukaryotic DNA mismatch repair (MMR) system contributes to maintaining genome
      integrity and DNA sequence fidelity in at least two important ways: by correcting
      errors arising during DNA replication, and also by preventing recombination
      events between divergent sequences. This study aimed to investigate the role of
      one key MMR gene in recombination. We obtained a mutant line in which the AtMLH1
      gene has been disrupted by the insertion of a T-DNA within the coding region.
      Transcript analysis indicated that no full-length transcript was produced in
      mutant plants. The loss of a functional AtMLH1 gene led to a significant
      reduction in fertility in both homozygotes and heterozygotes, and we observed a
      strong bias against transmission of the mutant allele. To investigate the role of
      AtMLH1 in mitotic recombination, the mutant was crossed to a series of
      recombination reporter lines. A strong decrease (72%) in the frequency of
      homologous recombination was observed in the mutant. However, the decline in
      recombination due to homeology was less severe in the Atmlh1 mutant than in a
      wild-type control. These data demonstrate a dual role for AtMLH1 in
      recombination: it is both required for recombination and acts to limit
      recombination between diverged sequences.

PMID- 17559506
TI  - Tuning the herbivore-induced ethylene burst: the role of transcript accumulation
      and ethylene perception in Nicotiana attenuata.
AB  - Caterpillar-induced ethylene emissions play an important role in plant-herbivore
      interactions. The ethylene burst that ensues after attack exceeds wound-induced
      ethylene emissions, but the mechanisms responsible remain unknown. Adding larval
      oral secretions (OS) to wounds mimics this ethylene burst. We demonstrate that
      fatty acid-amino acid conjugates are the responsible elicitors in Manduca sexta
      OS, and identify genes that are important in OS-elicited ethylene biosynthesis
      and perception in the larvae's host, Nicotiana attenuata, by examining the
      consequences of gene silencing on OS-elicited ethylene emissions, as quantified
      by photo-acoustic spectroscopy. OS elicitation increased transcript accumulation
      of ACC synthase (ACS), virus-induced gene silencing of ACS halved the OS-elicited
      ethylene release, and ACC supplementation to ACS-silenced plants restored
      ethylene emissions, demonstrating that ACS activity limits the rate of release.
      Silencing three wound- or OS-elicited ACC oxidase (ACO) genes with an ACO
      consensus fragment abolished the OS-elicited ethylene release. Virus-induced gene
      silencing of each ACO individually revealed that only NaACO2a and NaACO3 regulate
      the OS-elicited ethylene release. Transforming plants with various etr1-1
      constructs rendered them differentially 'deaf' to ethylene, and dramatically
      increased the OS-elicited ethylene burst, largely without regulating the
      transcripts of biosynthetic genes. The volume of the OS-elicited ethylene
      'scream' was proportional to the plant's deafness, as determined by 1-MCP
      treatments. We conclude that the OS-elicited ethylene burst is tuned by a tag
      team of transcriptional responses and ethylene perception. Ethylene signaling is
      shown to be essential in regulating two traits that are important in the N.
      attenuata-M. sexta interaction: OS-induced nicotine levels and floral longevity.

PMID- 17559507
TI  - Expression levels of barley Cbf genes at the Frost resistance-H2 locus are
      dependent upon alleles at Fr-H1 and Fr-H2.
AB  - Genetic analyses have identified two loci in wheat and barley that mediate the
      capacity to overwinter in temperate climates. One locus co-segregates with VRN-1,
      which affects the vernalization requirement. This locus is known as Frost
      resistance-1 (Fr-1). The second locus, Fr-2, is coincident with a cluster of more
      than 12 Cbf genes. Cbf homologs in Arabidopsis thaliana play a key regulatory
      role in cold acclimatization and the acquisition of freezing tolerance. Here we
      report that the Hordeum vulgare (barley) locus VRN-H1/Fr-H1 affects expression of
      multiple barley Cbf genes at Fr-H2. RNA blot analyses, conducted on a
      'Nure'x'Tremois' barley mapping population segregating for VRN-H1/Fr-H1 and Fr
      H2, revealed that transcript levels of all cold-induced Cbf genes at Fr-H2 were
      significantly higher in recombinants harboring the vrn-H1 winter allele than in
      recombinants harboring the Vrn-H1 spring allele. Steady-state Cbf2 and Cbf4
      levels were also significantly higher in recombinants harboring the Nure allele
      at Fr-H2. Additional experiments indicated that, in vrn-H1 genotypes requiring
      vernalization, Cbf expression levels were dampened after plants were vernalized,
      and dampened Cbf expression was accompanied by robust expression of Vrn-1. Cbf
      levels were also significantly higher in plants grown under short days than under
      long days. Experiments in wheat and rye indicated that similar regulatory
      mechanisms occurred in these plants. These results suggest that VRN-H1/Fr-H1 acts
      in part to repress or attenuate expression of the Cbf at Fr-H2; and that the
      greater level of low temperature tolerance attributable to the Nure Fr-H2 allele
      may be due to the greater accumulation of Cbf2 and Cbf4 transcripts during normal
      growth and development.

PMID- 17559508
TI  - Identification of genes expressed in the Arabidopsis female gametophyte.
AB  - The angiosperm female gametophyte typically consists of one egg cell, two
      synergid cells, one central cell, and three antipodal cells. Each of these four
      cell types has unique structural features and performs unique functions that are
      essential for the reproductive process. The gene regulatory networks conferring
      these four phenotypic states are largely uncharacterized. As a first step towards
      dissecting the gene regulatory networks of the female gametophyte, we have
      identified a large collection of genes expressed in specific cells of the
      Arabidopsis thaliana female gametophyte. We identified these genes using a
      differential expression screen based on reduced expression in determinant
      infertile1 (dif1) ovules, which lack female gametophytes. We hybridized ovule RNA
      probes with Affymetrix ATH1 genome arrays and validated the identified genes
      using real-time RT-PCR. These assays identified 71 genes exhibiting reduced
      expression in dif1 ovules. We further validated 45 of these genes using
      promoter::GFP fusions and 43 were expressed in the female gametophyte. In the
      context of the ovule, 11 genes were expressed exclusively in the antipodal cells,
      11 genes were expressed exclusively or predominantly in the central cell, 17
      genes were expressed exclusively or predominantly in the synergid cells, one gene
      was expressed exclusively in the egg cell, and three genes were expressed
      strongly in multiple cells of the female gametophyte. These genes provide
      insights into the molecular processes functioning in the female gametophyte and
      can be used as starting points to dissect the gene regulatory networks
      functioning during differentiation of the four female gametophyte cell types.

PMID- 17559509
TI  - Expression of the ASYMMETRIC LEAVES2 gene in the adaxial domain of Arabidopsis
      leaves represses cell proliferation in this domain and is critical for the
      development of properly expanded leaves.
AB  - The ASYMMETRIC LEAVES2 (AS2) gene, a member of the AS2/LOB gene family, and the
      ASYMMETRIC LEAVES1 (AS1) gene of Arabidopsis thaliana participate in the
      development of a symmetrical, expanded lamina. We report here the patterns of
      expression of these genes, and the importance of the sites of such expression in
      leaf development. Transcripts of both genes accumulated in the entire leaf
      primordia at early stages, but the patterns of accumulation changed as the leaves
      expanded. AS2 and AS1 transcripts were detected, respectively, in the adaxial
      domain and in the inner domain between the adaxial and abaxial domains of leaves.
      The ratios of numbers of adaxial cells to abaxial cells in cotyledons of
      corresponding mutant lines were greater than the ratios in wild-type cotyledons.
      The low levels of ectopic expression of AS2 under the control of the AS1 promoter
      in as2 mutant plants restored an almost normal phenotype in some cases, but also
      resulted in flatter leaves than those of wild-type plants. Strong expression of
      the construct in wild-type and as2 plants, but not as1 plants, resulted in the
      formation of narrow, upwardly curled leaves. Our results indicate that AS2
      represses cell proliferation in the adaxial domain in the presence of AS1, and
      that adaxial expression of AS2 at an appropriate level is critical for the
      development of a symmetrical, expanded lamina. Real-time RT-PCR analysis revealed
      that mutation of either AS2 or AS1 resulted in an increase in the levels of
      transcripts of ETTIN (ETT; also known as AUXIN RESPONSE FACTOR3, ARF3) and
      KANADI2 (KAN2), which are abaxial determinants, and YABBY5 (YAB5). Thus, AS2 and
      AS1 might negatively regulate the expression of these genes in the adaxial
      domain, which might be related to the development of flat and expanded leaves.

PMID- 17559510
TI  - Viral infection enables phloem loading of GFP and long-distance trafficking of
      the protein.
AB  - It is generally accepted that viral systemic infection follows the source-to-sink
      symplastic pathway of sugar translocation. In plants that are classified as
      apoplastic loaders, the boundary between the companion cell-sieve element (CC-SE)
      complex and neighboring cells is symplastically restricted, and the potential
      passage of macromolecules between the two domains has yet to be explored.
      Transgenic tobacco plants expressing green fluorescence protein (GFP) and
      cucumber mosaic virus (CMV)-encoded proteins fused to GFP under the control of
      the fructose-1,6-bisphosphatase (FBPase) promoter were produced in order to
      localize the encoded proteins in mesophyll and bundle sheath cells and to explore
      the influence of viral infection on the functioning of plasmodesmata
      interconnecting the two domains. GFP produced outside the vascular tissue could
      overcome the symplastic barrier between the CC-SE complex and the surrounding
      cells to enter the vasculature in CMV-infected plants. Grafting of control (non
      transgenic) tobacco scions to CMV-infected FBPase-GFP-expressing root stocks
      confirmed that GFP could move long distances in the phloem. No movement of the
      gfp mRNA was noticeable in this set of experiments. The ability of GFP to enter
      the vasculature and move long distances was also evident upon infection of the
      grafting plants with other viruses. These results provide experimental evidence
      for alteration of the functioning of plasmodesmata interconnecting the CC-SE
      complex and neighboring cells by viral infection to enable non-selective
      trafficking of macromolecules from the mesophyll into the sieve tube.

PMID- 17559511
TI  - A Pseudomonas syringae pv. tomato DC3000 mutant lacking the type III effector
      HopQ1-1 is able to cause disease in the model plant Nicotiana benthamiana.
AB  - The model pathogen Pseudomonas syringae pv. tomato DC3000 causes bacterial speck
      in tomato and Arabidopsis, but Nicotiana benthamiana, an important model plant,
      is considered to be a non-host. Strain DC3000 injects approximately 28 effector
      proteins into plant cells via the type III secretion system (T3SS). These
      proteins were individually delivered into N. benthamiana leaf cells via T3SS
      proficient Pseudomonas fluorescens, and eight, including HopQ1-1, showed some
      capacity to cause cell death in this test. Four gene clusters encoding 13
      effectors were deleted from DC3000: cluster II (hopH1, hopC1), IV (hopD1, hopQ1
      1, hopR1), IX (hopAA1-2, hopV1, hopAO1, hopG1), and native plasmid pDC3000A
      (hopAM1-2, hopX1, hopO1-1, hopT1-1). DC3000 mutants deleted for cluster IV or
      just hopQ1-1 acquired the ability to grow to high levels and produce bacterial
      speck lesions in N. benthamiana. HopQ1-1 showed other hallmarks of an avirulence
      determinant in N. benthamiana: expression in the tobacco wildfire pathogen P.
      syringae pv. tabaci 11528 rendered this strain avirulent in N. benthamiana, and
      elicitation of the hypersensitive response in N. benthamiana by HopQ1-1 was
      dependent on SGT1. DC3000 polymutants involving other effector gene clusters in a
      hopQ1-1-deficient background revealed that clusters II and IX contributed to the
      severity of lesion symptoms in N. benthamiana, as well as in Arabidopsis and
      tomato. The results support the hypothesis that the host ranges of P. syringae
      pathovars are limited by the complex interactions of effector repertoires with
      plant anti-effector surveillance systems, and they demonstrate that N.
      benthamiana can be a useful model host for DC3000.

PMID- 17559512
TI  - Attenuation of the hypersensitive response by an ATPase associated with various
      cellular activities (AAA) protein through suppression of a small GTPase, ADP
      ribosylation factor, in tobacco plants.
AB  - ATPase associated with various cellular activities (AAA) proteins are commonly
      distributed among eukaryotes, and are involved in a multitude of cellular
      functions. NtAAA1 is one such example, being involved in pathogen response in
      tobacco plants. When its activity was suppressed in RNAi transgenic tobacco
      plants, an elevated resistance to the pathogenic bacterium Pseudomonas syringae
      was observed in comparison with the wild type. As AAA proteins function through
      interaction with specific partners, NtAAA1-interacting proteins were screened by
      the yeast two-hybrid assay, and one particular gene encoding a small GTPase, an
      ADP ribosylation factor, was identified and designated as NtARF. Its specific
      binding to NtAAA1 was confirmed by in vitro pull-down assay, and their
      interaction was predominant between active forms of NtARF and NtAAA1, each bound
      to GTP and ATP, respectively. Their physical interaction in vivo around the
      plasma membrane was shown by fluorescence resonance energy transfer assays,
      suggesting their role in membrane trafficking. Transgenic tobacco plants
      constitutively expressing NtARF under the control of a cauliflower mosaic virus
      35S promoter exhibited spontaneous and wound-induced lesion formation, and
      enhanced resistance to pathogen attack. Expression of NtAAA1 in leaves of NtARF
      transgenic plants attenuated lesion and suppressed pathogen resistance. In wild
      type tobacco plants, transcripts of NtAAA1 and NtARF could be induced by ethylene
      and salicylic acid, respectively. These results suggest that NtAAA1 balances
      plant resistance through suppression of NtARF, and that the molecular basis for
      the known antagonistic actions of ethylene and salicylic acid in defense response
      could be partly attributable to these two proteins.

PMID- 17559513
TI  - RING-H2 type ubiquitin ligase EL5 is involved in root development through the
      maintenance of cell viability in rice.
AB  - Rice EL5 is an ATL family gene characterized by a transmembrane domain at the N
      terminal and a RING-H2 finger domain (RFD), which exhibits ubiquitin ligase (E3)
      activity. To elucidate the physiological roles of EL5, we analyzed transgenic
      rice plants overexpressing mutant EL5 proteins that are impaired in E3 activity
      to various degrees. Plants expressing EL5C153A and EL5W165A, which encode an
      inactive E3, showed a rootless phenotype accompanied by cell death in root
      primordia, and those expressing EL5V162A, with moderately impaired E3 activity,
      formed short crown roots with necrotic lateral roots. The dominant-negative
      phenotype was specifically observed in root meristems where EL5 is expressed, and
      not recovered by exogenous auxin. When wild-type EL5 was transcriptionally
      overexpressed, the EL5 protein was barely detected by Western blotting. Neither
      treatment with a proteasome inhibitor nor mutation of the sole lysine residue, a
      potential target of ubiquitination, resulted in increased EL5 accumulation,
      whereas mutations in the RFD led to increased EL5 accumulation. The stabilized
      EL5 without the RFD was localized in the plasma membrane. Deletion of the
      transmembrane domain prevented the EL5 from localizing in the membrane and from
      exerting an inhibitory effect on root formation. Deletion of the C-terminal
      region also neutralized the negative effect. We concluded that EL5 plays a major
      role as a membrane-anchored E3 for the maintenance of cell viability after the
      initiation of root primordial formation. In addition, we propose that EL5 is an
      unstable protein, of which degradation is regulated by the RFD in a proteasome
      independent manner.

PMID- 17559514
TI  - Ubiquitin C-terminal hydrolases 1 and 2 affect shoot architecture in Arabidopsis.
AB  - Ubiquitin C-terminal hydrolases (UCHs) are a subset of de-ubiquitinating
      proteases that release covalently linked ubiquitin (Ub), and as such play
      essential roles in recycling Ub and reversing the action of Ub conjugation. We
      show here that two related Arabidopsis UCHs, UCH1, and UCH2, are important for
      shoot development. The UCH1 and 2 genes are ubiquitously expressed, with the
      corresponding proteins present in both the cytoplasm and nucleus. Unlike their
      animal and fungal counterparts, we found no evidence that the Arabidopsis UCH1
      and 2 proteins stably associate with the 26S proteasome. Altering the levels of
      UCH1 and 2 has substantial effects on Arabidopsis shoot development, especially
      with respect to inflorescence architecture, with over-expression and double
      mutants enhancing and suppressing the outgrowth of cauline branches,
      respectively. Neither UCH1-over-expressing nor uch1-1 uch2-1 plants have
      detectably altered sensitivity to cytokinins or auxins individually, but exhibit
      an altered sensitivity to the ratio of the two hormones. UCH1-over-expressing
      plants show dramatically enhanced phenotypes when combined with auxin-insensitive
      mutants axr1-3 and axr2-1, suggesting that one or more aspects of auxin signaling
      are affected by this enzyme pair. Previous studies revealed that the
      ubiquitination and degradation of the AUX/IAA family of repressors is a key step
      in auxin signaling. Here, we show that turnover of a reporter fused to a
      representative AUX/IAA protein AXR3 is faster in the uch1-1 uch2-1 double mutant
      but slower in the UCH1 over-expression backgrounds. Taken together, our results
      indicate that de-ubiquitination helps to modify plant shoot architecture,
      possibly via its ability to directly or indirectly protect upstream target
      proteins involved in auxin/cytokinin signaling from Ub-mediated degradation.

PMID- 17559515
TI  - SB401, a pollen-specific protein from Solanum berthaultii, binds to and bundles
      microtubules and F-actin.
AB  - We characterize a novel, pollen-specific, microtubule-associated protein, SB401,
      found in Solanum berthaultii. This protein binds to and bundles taxol-stabilized
      microtubules and enhances tubulin polymerization in a concentration-dependent
      manner, particularly at lower temperatures. Electron microscopy revealed that the
      protein decorates the entire length of microtubules. Cross-linking and
      electrophoresis studies showed that SB401 protein forms dimers, and suggest that
      dimerization could account for bundling. Double immunofluorescent staining of
      pollen tubes of S. berthaultii showed that SB401 protein co-localized with
      cortical microtubule bundles. SB401 protein also binds to and bundles actin
      filaments, and could connect actin filaments to microtubules. SB401 protein had a
      much higher affinity for microtubules than for actin filaments. In the presence
      of both cytoskeletal elements, the protein preferentially bound microtubules to
      form bundles. These results demonstrate that SB401 protein may have important
      roles in organizing the cytoskeleton in pollen tubes.

PMID- 17559516
TI  - CyMATE: a new tool for methylation analysis of plant genomic DNA after bisulphite
      sequencing.
AB  - Cytosine methylation is a hallmark of epigenetic information in the DNA of many
      fungi, vertebrates and plants. The technique of bisulphite genomic sequencing
      reveals the methylation state of every individual cytosine in a sequence, and
      thereby provides high-resolution data on epigenetic diversity; however, the
      manual evaluation and documentation of large amounts of data is laborious and
      error-prone. While some software is available for facilitating the analysis of
      mammalian DNA methylation, which is found nearly exclusively at CG sites, there
      is no software optimally suited for data from DNA with significant non-CG
      methylation. We describe CyMATE (Cytosine Methylation Analysis Tool for Everyone)
      for in silico analysis of DNA sequences after bisulphite conversion of plant DNA,
      in which methylation is more divergent with respect to sequence context and
      biological relevance. From aligned sequences, CyMATE includes and distinguishes
      methylation at CG, CHG and CHH (where H = A, C or T), and can extract both
      quantitative and qualitative data regarding general and pattern-specific
      methylation per sequence and per position, i.e. data for individual sites in a
      sequence and the epigenetic divergence within a sample. In addition, it can
      provide graphical output from alignments in either an overview or a 'zoom-in'
      view as pdf files. Detailed information, including a quality control of the
      sequencing data, is provided in text format. We applied CyMATE to the analysis of
      DNA methylation at transcriptionally silenced promoters in diploid and polyploid
      Arabidopsis and found significant hypermethylation, high stability of the
      methylated state independent of chromosome number, and non-redundant patterns of
      mC distribution. CyMATE is freely available for non-commercial use at
      http://www.gmi.oeaw.ac.at/CyMATE.

PMID- 17559517
TI  - The rice bHLH protein OsIRO2 is an essential regulator of the genes involved in
      Fe uptake under Fe-deficient conditions.
AB  - Iron (Fe) deficiency is a major abiotic stress in crop production. Although
      responses to Fe deficiency in graminaceous plants, such as increased production
      and secretion of mugineic acid family phytosiderophores (MAs), have been
      described, the gene regulation mechanisms related to these responses are largely
      unknown. To elucidate the regulation mechanisms of the genes related to Fe
      acquisition in graminaceous plants, we characterized the Fe-deficiency-inducible
      basic helix-loop-helix transcription factor OsIRO2 in rice. In yeast cells,
      OsIRO2 functioned as a transcriptional activator. In rice, overexpression of
      OsIRO2 resulted in increased MAs secretion, whereas repression of OsIRO2 resulted
      in lower MAs secretion and hypersensitivity to Fe deficiency. Northern blots
      revealed that the expression of the genes involved in the Fe(III)-MAs transport
      system was dependent on OsIRO2. The expression of the genes for nicotianamine
      synthase, a key enzyme in MAs synthesis, was notably affected by the level of
      OsIRO2 expression. Microarray analysis demonstrated that OsIRO2 regulates 59 Fe
      deficiency-induced genes in roots. Some of these genes, including two
      transcription factors upregulated by Fe deficiency, possessed the OsIRO2 binding
      sequence in their upstream regions. OsIRO2 possesses a homologous sequence of the
      Fe-deficiency-responsive cis-acting elements (IDEs) in its upstream region. We
      propose a novel gene regulation network for Fe-deficiency responses, including
      OsIRO2, IDEs and the two transcription factors.

PMID- 17559518
TI  - A role for the AtMTP11 gene of Arabidopsis in manganese transport and tolerance.
AB  - The Arabidopsis AtMTP family of genes encode proteins of the cation diffusion
      facilitator (CDF) family, with several members having roles in metal tolerances.
      Four of the 11 proteins in the family form a distinct cluster on a phylogenetic
      tree and are closely related to ShMTP8, a CDF identified in the tropical legume
      Stylosanthes hamata that is implicated in the transport of Mn(2+) into the
      vacuole as a tolerance mechanism. Of these four genes, AtMTP11 was the most
      highly expressed member of the Arabidopsis subgroup. When AtMTP11 was expressed
      in Saccharomyces cerevisiae, it conferred Mn(2+) tolerance and transported Mn(2+)
      by a proton-antiport mechanism. A mutant of Arabidopsis with a disrupted AtMTP11
      gene (mtp11) was found to have increased sensitivity to Mn(2+) but not to Cu(2+)
      or Zn(2+). At a non-toxic but sufficient Mn(2+) supply (basal), the mutant
      accumulated more Mn(2+) than the wild type, but did not show any obvious
      deleterious effects on growth. When grown with Mn(2+) supplies that ranged from
      basal to toxic, the mutant accumulated Mn(2+) concentrations in shoots similar to
      those in wild-type plants, despite showing symptoms of Mn(2+) toxicity. AtMTP11
      fused to green fluorescent protein co-localized with a reporter specific for pre
      vacuolar compartments. These findings provide evidence for Mn(2+)-specific
      transport activity by AtMTP11, and implicate the pre-vacuolar compartments in
      both Mn(2+) tolerance and Mn(2+) homeostasis mechanisms of Arabidopsis.

PMID- 17559519
TI  - Use of a stress inducible promoter to drive ectopic AtCBF expression improves
      potato freezing tolerance while minimizing negative effects on tuber yield.
AB  - Solanum tuberosum is a frost-sensitive species incapable of cold acclimation. A
      brief exposure to frost can significantly reduce its yields, while hard frosts
      can completely destroy entire crops. Thus, gains in freezing tolerance of even a
      few degrees would be of considerable benefit relative to frost damage. The S.
      tuberosum cv. Umatilla was transformed with three Arabidopsis CBF genes (AtCBF1
      3) driven by either a constitutive CaMV35S or a stress-inducible Arabidopsis
      rd29A promoter. AtCBF1 and AtCBF3 over-expression via the 35S promoter increased
      freezing tolerance about 2 degrees C, whereas AtCBF2 over-expression failed to
      increase freezing tolerance. Transgenic plants of AtCBF1 and AtCBF3 driven by the
      rd29A promoter reached the same level of freezing tolerance as the 35S versions
      within a few hours of exposure to low but non-freezing temperatures. Constitutive
      expression of AtCBF genes was associated with negative phenotypes, including
      smaller leaves, stunted plants, delayed flowering, and reduction or lack of tuber
      production. While imparting the same degree of freezing tolerance, control of
      AtCBF expression via the stress-inducible promoter ameliorated these negative
      phenotypic effects and restored tuber production to levels similar to wild-type
      plants. These results suggest that use of a stress-inducible promoter to direct
      CBF transgene expression can yield significant gains in freezing tolerance
      without negatively impacting agronomically important traits in potato.

PMID- 17559520
TI  - Cytotoxic drug use in treatment of dogs and cats with cancer by UK veterinary
      practices (2003 to 2004).
AB  - OBJECTIVES: To describe the range and frequency of cytotoxic drugs prescribed
      within UK veterinary practices to treat dogs and cats with cancer, determine the
      effect of practice demographic variables on this practice and determine the
      frequency with which intravenous catheters were used during administration of
      parenteral cytotoxic drugs. METHODS: A postal survey of 1838 veterinary practices
      providing care for dogs and cats within the UK. RESULTS: Prescription of
      cytotoxic drugs to treat dogs and cats with cancer during the preceding 12 months
      was reported by 70.8 per cent practices. The most widely prescribed agents were
      cyclophosphamide (65.4 per cent) and vincristine (63.5 per cent). Twenty-three
      per cent of responding practices had prescribed an antitumour antibiotic and 8.3
      per cent had prescribed a platinum agent. The median frequency of prescription
      was between once a month and once every three months. Increasing frequency and
      range of cytotoxic drug prescription were associated with practice employment of
      higher numbers of veterinary surgeons and increased levels of pet insurance among
      practice clients. Almost a quarter of practices administering vesicant parenteral
      cytotoxic drugs failed to always use intravenous catheters to do so. CLINICAL
      SIGNIFICANCE: Prescription of cytotoxic drugs, and therefore the potential for
      occupational exposure of staff, was widespread among UK veterinary practices
      providing care for dogs and cats.

PMID- 17559521
TI  - Survival of 54 cats with oral squamous cell carcinoma in United Kingdom general
      practice.
AB  - OBJECTIVES: To determine the survival of 54 cats with histologically confirmed
      feline oral squamous cell carcinoma (FOSCC) treated in UK general practice and to
      determine factors predictive for survival. METHODS: Cases were identified from
      consecutive samples submitted for histological diagnosis. Observational and
      survival data were collated retrospectively from submitting practices.
      Immunohistochemical analysis of cyclooxygenase (COX) expression variables was
      available using previously published data. Kaplan-Meier product limit estimation
      for overall survival and Cox proportional hazards regression for potential
      explanatory variables were performed. RESULTS: The overall median survival time
      was 44 days [95 per cent confidence interval (CI): 31-79] and 1 year survival was
      9.5 per cent. Variables associated with survival were whether the cat was
      pedigree [hazard ratio (HR)=8.17, 95 per cent CI: 1.96-34.12], whether the cat
      received non-steroidal anti-inflammatory drug (NSAID) therapy after diagnosis
      (HR=0.46, 95 per cent CI: 0.21-0.98) and whether the COX-1 staining distribution
      was patchy rather than diffuse (HR=0.25, 95 per cent CI: 0.08-0.014). CLINICAL
      SIGNIFICANCE: This study suggests that although the prognosis for inoperable
      FOSCC remains poor, palliative treatments may offer a survival advantage that
      compares favourably with more aggressive treatment methods. Further work is
      needed to evaluate NSAID therapy in this disease, in particular to determine
      whether the potential survival advantage is because of an analgesic or anticancer
      effect or both. COX-1 distribution patterns may have a role as a prognostic
      indicator in this disease.

PMID- 17559522
TI  - Advances in the diagnosis and management of cutaneous mast cell tumours in dogs.
AB  - Mast cell tumours are one of the most common tumours of the canine skin and have
      a reputation for being difficult to manage because of their variable clinical
      presentation, behaviour and response to treatment. This review of recent
      literature on canine mast cell tumours suggests that the majority of such tumours
      may not be as bad as their reputation suggests. Most grade I and grade II tumours
      can be managed successfully by good surgery. Recent literature also calls into
      question the utility of clinical staging systems and the value of assessing
      surgical margins for prognosis and highlights the paucity of well-conducted, case
      controlled clinical trials in assessing the efficacy of medical management of
      high-risk tumours. In terms of more basic research, recent studies have
      implicated the stem cell factor receptor KIT as having a role in the aetiology of
      canine mast cell tumours and there appears to be an association between c-kit
      mutation and higher grade of tumour. This may offer a possible target for new
      therapeutic approaches.

PMID- 17559523
TI  - Clinical efficacy and safety of cefovecin in the treatment of canine pyoderma and
      wound infections.
AB  - OBJECTIVES: To determine the efficacy and safety of cefovecin in the treatment of
      bacterial skin infections in dogs. METHOD: Dogs with superficial or deep pyoderma
      or wounds/abscesses were enrolled in three separate studies. Dogs (354) were
      randomised to treatment and received either cefovecin administered by
      subcutaneous injection at 14 day intervals, as clinically necessary, or
      amoxicillin/clavulanic acid as oral tablets twice daily for 14 days. Courses of
      treatment were repeated at 14 day intervals up to a total of four courses.
      Clinicians responsible for assessing lesions were masked to treatment allocation.
      Only animals where the presence of a pretreatment bacterial pathogen was
      confirmed were included in the analysis of efficacy. Cases were evaluated for
      clinical efficacy at 28 days after initiation of the final course of treatment.
      Clinical efficacy was assessed by scoring the clinical signs typical of skin
      infections. RESULTS: Cefovecin demonstrated statistical non-inferiority compared
      with amoxicillin/clavulanic acid for all three clinical diagnoses; for cefovecin,
      up to 96.9 per cent efficacy was observed versus 92.5 per cent for
      amoxicillin/clavulanic acid. CLINICAL SIGNIFICANCE: Cefovecin was shown to be as
      effective as amoxicillin/clavulanic acid administered orally in the treatment of
      bacterial skin infections in dogs. Cefovecin offers the additional benefit of
      eliminating owner non-compliance.

PMID- 17559524
TI  - Seasonal and breed effects on reproductive parameters in bitches in the tropics:
      a retrospective study.
AB  - OBJECTIVES: To investigate the influence of season and breed on reproductive
      parameters in bitches raised under tropical climatic conditions. METHODS: Over a
      seven year period, from 1998 to 2004, 310 oestrous periods of 53 bitches were
      observed. The dogs were of various breeds; dobermann (number of bitches/number of
      oestrous cycles) (n=2/19), German shepherd dog (n=35/211), Labrador retriever
      (n=14/68) and Rottweiler (n=2/12). In 250 of the 310 oestrous periods, natural
      matings took place on days 9 and 11 after the onset of pro-oestrus. The whelping
      rate was analysed for bitches of each breed. Variables, including breed and the
      whelping rate, by month of the year, were used for analysis of the inter-oestrus
      interval, gestation length, total number of pups born, number of live pups born
      and the weight of the pups at birth. RESULTS: A low frequency of oestrous
      activity was found during the summer. Breeding dogs in the summer resulted in a
      low whelping rate. No difference (P>0.05) was seen in the whelping rate of each
      breed: dobermann (70.5 per cent), German shepherd dog (61.5 per cent), Labrador
      retriever (67.9 per cent) and Rottweiler (100 per cent). The Labrador retriever
      had a longer inter-oestrus interval (252 [114] and 190 [61] days) (P<0.01) and a
      larger litter size (8.2 [1.8] and 6.6 [2.8]) (P<0.05) than the German shepherd
      dog. CLINICAL SIGNIFICANCE: The environmental factors in summer tend to reduce
      oestrus incidence and fertility in the bitches. According to litter size, the
      Labrador retriever seems to have a more efficient reproductive performance than
      the German shepherd dog. The Labrador retriever had a longer inter-oestrus
      interval than the German shepherd dog.

PMID- 17559525
TI  - Ankylosis of tarsometatarsal luxations using external fixation.
AB  - This report evaluates the suitability of using an external fixator as the sole
      means of correcting tarsometatarsal luxations. Four dogs were included in this
      report. Each dog weighed more than 20 kg and had sustained a tarsometatarsal
      luxation with plantar, medial or lateral instability. The luxations were
      immobilised with an external fixator for between 12 and 17 weeks. The surgery did
      not involve soft tissue dissection, debridement of articular cartilage or a
      cancellous bone graft and no external coaptation was used postoperatively. The
      result of this treatment was to ankylose the tarsometatarsal luxation and allow
      the dogs to return to normal function.

PMID- 17559526
TI  - Problem-based learning in undergraduate dental education: faculty development at
      the University of Southern California School of Dentistry.
AB  - The University of Southern California School of Dentistry (USCSD) seeks to
      educate oral health professionals with a balanced curriculum covering health
      promotion, risk assessment and disease prevention, diagnostics, treatments, and
      therapeutics. Based on critical analyses of a 5-year educational demonstration
      project, the USCSD proposed to use problem-based learning (PBL) to achieve its
      goals. Among the many changes required to convert a traditional dental
      educational curriculum to PBL, none is more important than that of faculty
      development. To achieve this, the USCSD Curriculum Subcommittee on Faculty
      Development, Mentoring, and Evaluation has designed and implemented a series of
      workshops to train its faculty as facilitators. There are four Core Skills
      Workshops: PBL Process Workshop, Facilitation of Learning Workshop, Student
      Assessment and Feedback Workshop, and PBL in the Clinical Environment.

PMID- 17559527
TI  - A technique to obtain stable centric occlusion records using impression plaster.
AB  - Recording the maxillomandibular relationship is often a challenge. In situations
      where there is vertical support but no horizontal stability, and the space
      between posterior teeth of opposing jaws is not adequate for an interocclusal
      record, impression plaster can be used. Despite limited clinical use, impression
      plaster is known for its stability. With this technique, the interocclusal record
      is obtained by applying the material to the buccal surfaces of the posterior
      teeth, resulting in a precise and stable cast relationship.

PMID- 17559528
TI  - The use of a diagnostic matrix in the management of the severely worn dentition.
AB  - The management of the interim phase of a complete oral rehabilitation in patients
      with severely worn dentition is often challenging due to loss of occlusal
      vertical dimension, loss of tooth structure, uneven wear of teeth creating an
      uneven plane of occlusion, and para-functional habits. This paper will
      demonstrate how a clear thermo-forming matrix fabricated from the diagnostic wax
      up can be used as a guide to facilitate treatment.

PMID- 17559529
TI  - Prosthodontists in private practice: current and future conditions of practice in
      the United States (part I).
AB  - PURPOSE: The purpose of this study was to use data from surveys of
      prosthodontists to examine the current conditions and characteristics of
      prosthodontists in private practice in the United States. MATERIALS AND METHODS:
      Characteristics of prosthodontists and conditions of practice are based on the
      2002 Survey of Prosthodontists and the 2005 Survey of Prosthodontists. Both
      surveys were conducted by the American College of Prosthodontists. Several
      characteristics of private practice/practitioners are estimated including age,
      gender, number of patient visits, hours in the practice, employment of staff, and
      financial conditions (gross receipts, expenses of the practice, and net income of
      prosthodontists) RESULTS: In 2004, the average age of private practitioners was
      50 years. Years since graduation from dental school averaged 23.4 years, and
      years since completion of residency was 18.3 years. Prosthodontists spent an
      average of 35.7 hours per week in the office and 29.5 hours treating patients. In
      2004, the average gross revenue per owner of a private practice reached $782,130,
      and mean net income was $258,490. The largest percentage of prosthodontist time
      was spent providing six procedures including fixed prosthodontics, implant
      services, complete dentures, operative care, diagnosis, and partial dentures.
      CONCLUSION: The United States spends about $1.8 billion on prosthodontic services
      provided by prosthodontists in private practice. Prosthodontists spend $1.1
      billion dollars in expenses and treat an estimated 1.1 million patients per year.

PMID- 17559530
TI  - Occlusal changes following posterior tooth loss in adults. Part 1: a study of
      clinical parameters associated with the extent and type of supraeruption in
      unopposed posterior teeth.
AB  - PURPOSE: One of the barriers to restoring an edentulous space may be the
      supraeruption of an unopposed tooth to occupy some or all of the space needed for
      prosthetic replacement. The aim of this study was to determine the extent and
      type of supraeruption associated with unopposed posterior teeth and to
      investigate the relationship between these and oral and patient factors.
      MATERIALS AND METHODS: Diagnostic casts of 100 patients with an unopposed
      posterior tooth and of 100 control patients were scanned and analyzed to record
      the extent of supraeruption, together with other clinical parameters. The type of
      eruption present was defined for each subject as Periodontal Growth, Active
      Eruption, or Relative Wear. Generalized Linear Models were developed to examine
      associations between the extent and type of supraeruption and patient or dental
      factors. The extent of supraeruption for an individual was modeled to show
      association between the degree of supraeruption and clinical parameters. Three
      models were produced to show associations between each type of supraeruption and
      clinical parameters. RESULTS: The mean supraeruption for subjects was 1.68 mm (SD
      0.79, range 0 to 3.99 mm) and for controls, 0.24 mm (SD 0.39, range 0 to 1.46
      mm). The extent of supraeruption was statistically greater in maxillary unopposed
      teeth than in mandibular unopposed teeth. Supraeruption was found in 92% of
      subjects' unopposed teeth. CONCLUSIONS: A Generalized Linear Model could be
      produced to demonstrate that the clinical parameters associated with
      supraeruption are periodontal growth, attachment loss, and the lingual movement
      of the tooth distal to the extraction site. Three types of supraeruption, which
      may be present singly, or in combination, can be identified. Active eruption has
      an association with attachment loss. Periodontal growth has an inverse
      association with attachment loss, is more prevalent in younger patients, in the
      maxilla, in premolars, and in females. Relative wear has an association with
      increasing age and is more prevalent in unopposed mandibular teeth.

PMID- 17559531
TI  - Prognosis for abutment teeth of removable dentures: a retrospective study.
AB  - PURPOSE: This retrospective study evaluates the clinical success of conical crown
      retained removable dentures. MATERIALS AND METHODS: Ninety-seven patients were
      treated with 97 dentures at the University of Frankfurt, Department of
      Prosthodontics, between 1993 and 2000. The average observation period was 4.9 +/-
      2.8 years. The dentures were supported by 445 natural abutment teeth. To evaluate
      the long-term success of the restorations, the variables abutment loss, tooth
      mobility, mean probing depths, and radiological bone loss were used. Data were
      obtained by one clinical examiner at baseline, by systematic evaluation of
      patient records, and at clinical re-examinations. Survival-time methods were used
      to analyze time-to-event data. Specifically, the Cox model with frailty term was
      applied to account for correlations between intra-patient survival data. Thirty
      abutment teeth had to be extracted during the observation period. RESULTS:
      Statistical analysis showed no significant effects of the variables tooth
      mobility (p= 0.42), mean probing depths (p= 0.23), and radiological bone loss (p=
      0.59) on the time to tooth extraction. For the non-extracted abutment teeth
      significant changes during time for the variables tooth mobility (p < 0.0001) and
      radiological bone loss (p= 0.0240) were observed. CONCLUSION: Removable partial
      dentures retained by conical crowns have a favorable clinical prognosis.

PMID- 17559532
TI  - Dimensional change of laser-welded gold alloy induced by heat treatment.
AB  - PURPOSE: This study examined the effects of laser welding and heat treatment on
      the dimensional change of cast gold alloy frameworks. MATERIALS AND METHODS:
      Pairs of cast gold alloy plates were matched, fixed in a jig, and welded in a
      laser-welding machine at constant welding parameters. The specimens were welded
      unilaterally (on one surface) or bilaterally (on two surfaces) with five spots as
      follows: two ends fixed/unilaterally welded (A); two ends fixed/bilaterally
      welded (AA); one end fixed/unilaterally welded (B); two ends fixed/welded on one
      surface and then one end fixed/welded on the opposite surface (AB); or one end
      fixed/bilaterally welded (BB). The dimensional change was determined by measuring
      the gap between the jig base and one end of the specimen after each welding
      application. Dimensional change was also measured after two different heat
      treatments (softening and hardening). The results were analyzed using a two-way
      ANOVA and Duncan's test (p < 0.05). RESULTS: The dimensional change of the
      specimens fixed at only one end on either surface (AB, B, and BB) was higher
      compared with the two ends-fixed specimens (A and AA) after laser welding. The
      heat treatments also increased the dimensional change in all groups except for
      the B group. The dimensional change was similar for each fixing method between
      the two types of heat treatment. CONCLUSIONS: The method of fixing the specimens
      in the jig significantly affected the amount of dimensional change of the gold
      alloys. The heat treatments of the laser-welded specimens increased the
      dimensional change by releasing the residual stress.

PMID- 17559533
TI  - Measuring the radiopacity of luting cements, dowels, and core build-up materials
      with a digital radiography system using a CCD sensor.
AB  - PURPOSE: This study assessed the radiopacity of five luting cements, five dowels,
      and five core build-up materials using two target distances. MATERIALS AND
      METHODS: Materials were analyzed using a modified version of ISO protocol 4049.
      samples 1 mm thick were digitally radiographed alongside a stepwedge of aluminum
      alloy 1100 using a Trophy RVG-4 CCD sensor and 70 kVp X-ray generator. The gray
      scale values of the stepwedge and sample were converted to X-ray absorbencies.
      The relationship between X-ray absorbance and aluminum thickness was linear for
      thicknesses less than 10 mm and followed a power-law relationship above 10 mm.
      These relations were used to convert the absorbencies of the samples into
      aluminum thicknesses. The radiopacity data was subjected to ANOVA/Student-Newman
      Keuls testing. RESULTS: All materials were more radiopaque than equivalent
      thicknesses of aluminum. Each product category contained a wide range of
      radiopacities. Syringe-dispensed materials tended to be less radiopaque than
      materials dispensed by mechanically assisted syringe or mixed by hand (p < 0.01).
      Target distance did not affect the measured radiopacity so long as the exposure
      time was suitably adjusted (p= 0.86). CONCLUSIONS: All luting cements and core
      materials met or exceeded the ISO minimums. The tested metal-reinforced glass
      ionomer core build-up materials were extremely radiopaque. Some publications
      suggest that excessively radiopaque core materials can hinder a clinician's
      ability to spot voids or marginal defects.

PMID- 17559534
TI  - The effect of a constant electrical field on osseointegration after immediate
      implantation in dog mandibles: a preliminary study.
AB  - PURPOSE: The long time span between insertion of implants and functional
      rehabilitation often inconveniences patients. Accelerating bone growth around
      dental implants can shorten this time span. This in vivo study evaluated the
      effect of a constant electrical field on bone growth around dental implants.
      MATERIALS AND METHODS: Four mongrel dogs were used in this study. Sixteen dental
      implants were placed immediately after extraction of the first premolar and molar
      teeth. A constant electrical field (CEF) generator was placed in the
      mucoperiostal pouch created from the subperiostral dissection under the inferior
      border of the dog's mandible and connected to the experiment side fixtures. CEF
      provided 3 V of electrical potential during osseointegration. Histologic sections
      were stained with hematoxylin-eosin and observed under light microscopy. The
      sections were analyzed histomorphometrically to calculate the amount of newly
      formed bone. Statistical analysis was performed with SPSS 11.0 computer software
      (alpha= 0.05). RESULTS: At the end of the first stage of the osseointegration (90
      days) CEF group sections showed enhanced growth of the trabeculae compared with
      the control group. Statistical analysis revealed significant differences between
      experimental and control groups. Bone contact ratio was statistically significant
      in the experimental group (p= 0.001). An increase in the local bone formation and
      bone contact ratio was observed with direct electrical stimulation of the implant
      and the bone area around the implant. CONCLUSION: Minimal direct electrical
      current, which can produce an electrical field around the implant, can increase
      the amount of bone formation and decrease the time of osseointegration.

PMID- 17559535
TI  - Variations of L*a*b* values among Vitapan Classical Shade Guides.
AB  - PURPOSE: To measure the variations in L*a*b* values of a group of 25 guides and
      to assess whether shade guides are indeed interchangeable. MATERIALS AND METHODS:
      The L*a*b* values of individual shade tabs were measured with a LabScan(tm) XE
      scanning spectrocolorimeter (SSC) with a special attachment for reproducibly
      positioning shade tabs. Each shade guide (Vitapan Classical, Vident) contained 16
      shade tabs. Absolute calibration of the SSC was performed with color tiles
      traceable to NIST. One shade guide was used to determine the reproducibility of
      the experimental method by measuring and then removing each shade tab of the
      standard 10 times. This assessed the variations in observed values induced by the
      measurement method and the geometry of the specimens. The entire sample consisted
      of 25 shade guides. The tabs of each of the 25 shade guides were read five times
      in the SSC, without moving the specimen. Measurements and calculations of E, L*,
      a*, and b* were performed using Universal Software V4.10 (Hunter Associates
      Laboratory). The mean, standard deviation, and range were determined of the E,
      L*, a*, and b* values for each one of the 16 shades in the shade guides.
      Differences in color are expressed as DeltaE in color science. The standard
      deviation of E (E(sd)) and the range of E (E(r)) for each of the shades were used
      as a DeltaE value to assess color differences. RESULTS: For the reproducibility
      measurements, the shades had values for E(r) varying from 0.08 to 0.69, and E(sd)
      between 0.02 and 0.22. This established the detection limit for our method for
      each of the shades. For the group of 25 shade guides, E(r) varied from 0.75 to
      3.05, and E(sd) from 0.22 to 0.54. The difference in value of E(r) obtained from
      the reproducibility test and the E(r) of the group of 25 guides is significant at
      p < 0.05. The same was found for E(sd). The largest reproducible E(r) observed
      was 3.05 for shade C1. CONCLUSIONS: The differences observed between shade guides
      are larger than the variations induced by the experimental method. The difference
      in E values for the shades C1 and C2 is 2.19; hence the observed E(r) of 3.05
      between shade tabs of the same shade (C1) is larger than the changes in color
      between shades. This large a variation in what are claimed as identical shade
      tabs is deemed of clinical importance, and therefore, the shade guides should not
      be considered interchangeable.

PMID- 17559536
TI  - Surface quality and long-term dimensional stability of current elastomeric
      impression materials after disinfection.
AB  - PURPOSE: The objectives of this investigation were to evaluate the effect of
      disinfection on surface quality and dimensional stability of more recent,
      reformulated vinylpolysiloxane (VPS) and polyether (PE) materials. METHODS: Using
      ANSI/American Dental Association (ADA) specification 19 protocols, 50 impressions
      of stainless steel dies were made with each material. Ten impressions of each
      material were randomly assigned to a treatment group: (1) no disinfectant; (2) 10
      minute dual phenol immersion; (3) 1-hour dual phenol; (4) 10-minute sodium
      hypochlorite (NaOCl); and (5) 1-hour NaOCl. Impression surface quality
      immediately after disinfection was categorized as smooth/shiny, matte, or
      wrinkled/sticky. Dimensional stability was evaluated by measuring dimensional
      accuracy according to specification 19 after 24-hour, 1-week, and 2-week storage
      at ambient laboratory conditions. RESULTS: The PE material surface quality was
      significantly affected (Pearson Chi-square, p<or= 0.05) by NaOCl with a mottled
      surface on 30% of the impressions after 10-minute immersion and a matte/sticky
      surface on 100% of the PE impressions after 1-hour immersion. Separate 2-factor
      analyses of variance (ANOVA) and Bonferroni post hoc tests of dimensional
      accuracy within each material indicated a significant difference (p<or= 0.05)
      between non-disinfected and disinfected PE impressions, which exhibited
      expansion. There were also significant differences (p<or= 0.05) in both VPS and
      PE dimensional accuracy as a function of measurement time related to increasing
      shrinkage over time in non-disinfected and disinfected impressions. CONCLUSIONS:
      Despite PE expansion following disinfection and continued shrinkage of both the
      non-disinfected and disinfected VPS and PE impressions over a 2-week period, all
      dimensional accuracy measurements met the ADA standard, <or=0.5% dimensional
      change. Based on this evidence, neither NaOCl nor dual phenol disinfectants used
      for varying time periods adversely affected the dimensional stability of the more
      recent formulations of VPS and PE; however, Impregum PentaSoft PE surface quality
      appeared to be adversely affected by increasing exposure to NaOCl.

PMID- 17559537
TI  - Pre- and post-set hydrophilicity of elastomeric impression materials.
AB  - PURPOSE: To evaluate the hydrophilicity of one polyether, four poly(vinyl
      siloxanes), and one condensation silicone before and after setting under
      simulated clinical conditions, and to correlate the findings to the contact angle
      values of these materials. MATERIALS AND METHODS: The hydrophilicity before and
      after setting, as well as the contact angle values of the elastomeric impression
      materials were evaluated. Part I: A freshly extracted tooth, which was prepared
      for a full coverage restoration, was kept in saliva for 15 minutes and was then
      rinsed for 10 seconds. Impressions were taken without any drying of the tooth. A
      total of ten samples were taken for each material. The specimens were evaluated
      at a 10x magnification for defects. Part II: After the evaluation, the
      impressions were poured with a type IV dental stone and were left for 1 hour
      before separation. The stone specimens were then evaluated at a 10x magnification
      for negative voids. A total of 60 specimens were tested. Part III: Sixty
      identical 10 x 10 x 4 mm(2) plastic molds were used for the fabrication of the
      impression material specimens. Contact angle measurements of each specimen were
      made 1 hour after separation from the plastic mold. A calibrated pipette was used
      to place a drop (0.05 ml) of saturated calcium sulfate dehydrate onto each
      specimen. Digital images were taken for each specimen, and contact angle values
      were measured with appropriate software. RESULTS: Part I: One-way ANOVA revealed
      significant differences among the materials (F = 15.526, p < 0.0005). Polyether
      had the fewest voids. The poly(vinyl siloxanes) did not present any significant
      differences among them, according to Tukey's HSD test (p < 0.05). Part II: One
      way ANOVA revealed significant differences among the materials (F = 46.164, p <
      0.0005). Polyether (Impregum) was the material which produced stone specimens
      with the fewest voids. Part III: One-way ANOVA indicated significant differences
      among the elastomeric impression materials (F = 494.918, p < 0.0005). Polyether
      displayed the smallest contact angle values. CONCLUSIONS: Polyether was the most
      hydrophilic of all materials tested.

PMID- 17559538
TI  - Osteoblast differentiation is enhanced in rotary cell culture simulated
      microgravity environments.
AB  - PURPOSE: As the aging population increases, more people will become reliant on
      regenerative dental medicine for implant therapy. The objective of this study was
      to test the hypothesis that 3D rotary cell culture (RCC) environments created by
      simulated microgravity would enhance osteogenic gene expression using integrin
      mediated pathways. MATERIALS AND METHODS: Human embryonic palatal mesenchymal
      (HEPM, ATCC 1486) pre-osteoblasts were cultured in either RCC to create 3D
      environments or in 2D monolayers for 72 hours. Gross phenotypic analysis was
      performed using Alizarin Red S staining for calcium and microscopy. Real-time PCR
      analysis was used to detect differences in osteoblast gene expression. Aggregates
      developed in 3D RCC environments were treated with or without antibody to the
      collagen-I integrin receptor alpha2beta1 to determine whether this molecular
      pathway might contribute to the development of a mineralized matrix. RESULTS:
      Microscopic analysis demonstrated that RCC environments promoted 3D aggregate
      formation by 72 hours without any scaffold. The mass appeared osseous-like with a
      white, shiny, translucent surface. The center was amorphous with areas of
      vacuolization, tubule-like structures, and fibrous-like extensions. Real-time PCR
      data showed that 3D environments enhanced osteogenic gene expression as compared
      with 2D monolayer culturing conditions. At 72 hours, changes in levels of
      osteogenic gene expression were noted. Cbfa1, a necessary transcription factor
      for osteoblast differentiation, was expressed 33% higher (p= 0.26); Collagen 1,
      69% higher (p= 0.05); Osterix, 49% higher (p= 0.001); and BSPII, 54% higher (p=
      0.001) than osteoblasts cultured for 72 hours in standard 2D monolayer
      conditions. When cultured in the presence of collagen alpha2beta1 integrin
      receptor antibody, 3D aggregates had decreased levels of mineralization as
      compared with non-treated aggregates. CONCLUSION: RCC enhances osteoblast
      differentiation using integrin mediated pathways.

PMID- 17559539
TI  - The metamorphic fate of supernumerary caudal vertebrae in South Asian litter
      frogs (Anura: Megophryidae).
AB  - Tadpoles of the Megophryidae, a South Asian family of litter frogs, are unique
      among anurans by virtue of their expanded caudal skeletons, which include
      supernumerary vertebral centra. The number of these vertebrae varies widely
      within the family, with tadpoles of Leptobrachella having as many as 30 and
      Leptolalax only five. Vertebral morphology is also quite variable, ranging from
      complete, perichordal centra to fragmentary ossifications. This variation in the
      caudal osteology of larval megophryids, however, is not manifested in the adult
      morphology. Post-metamorphic litter frogs have a typical anuran axial skeleton,
      invariably comprising eight presacral vertebrae, a single sacral vertebra and,
      postsacrally, the urostyle. To resolve this incongruity between life phases and
      to determine the precise metamorphic fate of supernumerary caudal vertebrae in
      megophryids, we examined metamorphic specimens from the genera Leptobrachella,
      Leptolalax, Ophryophryne and Megophrys. In all four, the caudal larval skeleton
      undergoes massive reduction, leaving only the coccyx and hypochord untouched.
      Caudal centra are apparently degraded by osteoclasts, which have not previously
      been implicated in vertebral remodelling during anuran metamorphosis. In
      Megophrys and Ophryophryne metamorphs, presacral centra also undergo resorption,
      consistent with an epichordal mode of centrum formation. The conservation of
      megophryid adult axial osteology in the face of extensive larval skeletal
      diversity reveals the role of metamorphosis in constraining anuran morphology.

PMID- 17559540
TI  - Clinicopathological significance of survivin expression in patients with
      hepatocellular carcinoma.
AB  - AIMS: Survivin, a newly discovered member of the inhibitor of apoptosis protein
      family, is suggested to be involved in liver carcinogenesis. The aim was to
      investigate the clinical significance of survivin expression in resected
      hepatocellular carcinoma (HCC) and paired adjacent non-tumour tissue. METHODS AND
      RESULTS: Immunohistochemistry, reverse transcriptase-polymerase chain reaction
      and Western blots were used to examine survivin mRNA and protein levels in 94
      specimens of HCC tissues at different TNM stages and the data were correlated
      with the clinicopathological profiles. Patients were categorized into those with
      high tumour survivin protein levels (T-N >or= -1) and those with low levels (T-N
      < -1). Follow-up data were collected prospectively. mRNA levels of survivin and
      its splice variants in tumour tissue were significantly higher than in paired non
      tumour tissue. However, survivin protein levels in paired non-tumour tissue were
      significantly higher than in tumour tissue from all three TNM stages.
      Additionally, high tumour survivin protein levels (T-N >or= -1) correlated with a
      better prognosis and low levels (T-N < -1) with a worse survival rate.
      CONCLUSIONS: High cytoplasmic survivin protein levels in HCC tissues seem to be
      an indicator of better prognosis in HCC patients after resection.

PMID- 17559541
TI  - c-FLIP expression in colorectal carcinomas: association with Fas/FasL expression
      and prognostic implications.
AB  - AIMS: Disruption of apoptotic cell death has been implicated in tumour
      aggressiveness in colonic carcinogenesis. The Fas-Fas ligand (FasL) system is
      involved in the execution of apoptosis induced by the immune system. c-FLIP
      protein constitutes an inhibitor of Fas and other (TRAIL) death receptor-mediated
      apoptosis. The aim of this study was to investigate the simultaneous expression
      of Fas, FasL and c-FLIP in relation to standard clinicopathological parameters
      and patients' outcome in colorectal cancer. METHODS AND RESULTS: Levels of Fas,
      FasL and c-FLIP protein expression were quantified immunohistochemically in
      paraffin-embedded tissues from 90 patients. Immunopositivity was detected for
      Fas, FasL and c-FLIP in 71%, 35.5% and 68.8% of cases, respectively. Concurrent
      expression of Fas/FasL was seen in 28 samples (31%), of which 24 (85.7%) also
      displayed c-FLIP positivity (P = 0.04). c-FLIP overexpression (> 10%) tended to
      prevail marginally in higher stage tumours (P = 0.09). Additionally, FasL and c
      FLIP adversely affected survival on both univariate (P = 0.001 and P = 0.0024,
      respectively) and multivariate analysis [hazard ratio (HR) 3.491, P = 0.005 and
      HR 2.960, P = 0.036, respectively]. CONCLUSIONS: The frequent expression and
      coexpression of Fas, FasL and c-FLIP in colorectal carcinoma implicates c-FLIP as
      an inhibitor of the Fas-FasL-induced death pathway in these tumours. Moreover, c
      FLIP conveys independent prognostic information in the presence of classical
      prognosticators.

PMID- 17559542
TI  - Prenatal alcohol exposure affects frontal-striatal BOLD response during
      inhibitory control.
AB  - BACKGROUND: Prenatal alcohol exposure can lead to widespread cognitive impairment
      and behavioral dysregulation, including deficits in attention and response
      inhibition. This study characterized the neural substrates underlying the
      disinhibited behavioral profile of individuals with fetal alcohol spectrum
      disorders (FASD). METHODS: Children and adolescents (ages 8-18) with (n=13) and
      without (n=9) histories of heavy prenatal alcohol exposure underwent functional
      magnetic resonance imaging while performing a response inhibition (go/no-go)
      task. RESULTS: Despite similar task performance (mean response latency,
      performance accuracy, and signal detection), blood oxygen level-dependent (BOLD)
      response patterns differed by group. Region-of-interest analyses revealed that
      during portions of the behavioral task that required response inhibition, alcohol
      exposed participants showed greater BOLD response across prefrontal cortical
      regions (including the left medial and right middle frontal gyri), while they
      showed less right caudate nucleus activation, compared with control participants.
      CONCLUSIONS: These data provide an account of response inhibition-related brain
      functioning in youth with FASD. Furthermore, results suggest that the frontal
      striatal circuitry thought to mediate inhibitory control is sensitive to alcohol
      teratogenesis.

PMID- 17559543
TI  - Effects of drivers' license suspension policies on alcohol-related crash
      involvement: long-term follow-up in forty-six states.
AB  - BACKGROUND: We evaluated the effects of driving under the influence (DUI)
      mandatory preconviction and postconviction drivers' license suspension laws in
      each of 46 U.S. states using 1 to 2 decades of long-term follow-up data on fatal
      car crashes. State-specific results were combined using meta-analytic techniques,
      and provide a direct test of the concept of celerity--time between offending
      behavior and consequent punishment--from deterrence theory. METHODS: Four key
      outcome measures of monthly fatal alcohol-related crash involvement were examined
      using data from January 1976 through December 2002: single-vehicle nighttime,
      breath or blood alcohol concentration (BAC)=0.01 to 0.07, BAC=0.08 to 0.14, and
      BAC>or=0.15 g/dL. Missing BAC test data for some individual cases were filled
      using multiple imputation methods, and consequent increases in standard errors
      were incorporated into subsequent analyses. Separate ARIMA models were estimated
      for each state, including controls for state-specific levels of crash involvement
      over time due to other factors and effects of other major DUI countermeasures.
      Estimates were pooled across states using inverse variance weighting methods.
      RESULTS: Administrative or preconviction drivers license suspension policies have
      statistically significant and substantively important effects in reducing alcohol
      related fatal crash involvement by 5%, representing at least 800 lives saved per
      year in the United States. Moreover, these laws have similar effects on drivers
      at all drinking levels--from lower-risk drivers below the legal alcohol limit to
      drivers at extreme levels of intoxication. In clear contrast, postconviction
      license suspension policies have no discernable effects. CONCLUSIONS: The
      effectiveness of a deterrence policy appears to be more strongly affected by
      celerity-the speed by which punishment is applied after the offending behavior-
      than by the high severity of the penalty. This finding could be fruitfully
      applied to other areas of alcohol control policy and laws and regulations in
      general.

PMID- 17559544
TI  - Simplifying alcohol assessment: two questions to identify alcohol use disorders.
AB  - BACKGROUND: Previous work has validated a single question to screen for hazardous
      or harmful drinking, but identifying those patients who have an alcohol use
      disorder (AUD) among those who screen positive is still time consuming. We
      therefore sought to develop and validate a brief assessment instrument using DSM
      IV criteria for use in primary care medical practice. METHODS: Four cross
      sectional surveys of past-year drinkers. The developmental sample included
      patients presenting to emergency departments with an acute injury. The second
      sample, from the same study, was recruited by random-digit dialing. The third
      sample was recruited in 5 family medicine practices in Georgia. The fourth sample
      was the National Epidemiologic Survey on Alcohol and Related Conditions.
      Interviews with the first 3 samples used the Diagnostic Interview Schedule. The
      National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) used the
      Alcohol Use Disorder and Associated Disabilities Interview Schedule. RESULTS: Two
      constructs with promising test characteristics were identified: recurrent
      drinking in hazardous situations and drinking more than intended. Among those who
      screened positive with the single question in the developmental sample (N=959),
      if either of the 2 items was positive, the sensitivity for current AUD was 95%
      and the specificity was 77%. In the second (N=494) and third (N=280) samples, the
      sensitivity was 94 and 95% and the specificity was 62 and 66%, respectively,
      among those with a positive screen. In the NESARC sample, including those with at
      least 1 occasion in the past year of drinking 5 or more drinks (N=7,890), the
      sensitivity and specificity were 77 and 86%, respectively. CONCLUSIONS: The
      sensitivity and specificity of these 2 items across 4 samples suggest that they
      could be formulated into 2 questions, potentially providing busy primary care
      clinicians with an efficient, reasonably accurate assessment instrument to
      identify AUD among those patients who screen positive with the single screening
      question.

PMID- 17559545
TI  - Polyphenolic grape extract inhibits platelet activation through PECAM-1: an
      explanation for the French paradox.
AB  - BACKGROUND: Moderate and prolonged consumption of red wine is associated with
      decreased cardiovascular morbidity and mortality. Inhibition of platelet
      functions by ingredients in red wine is thought to be one of the causes. However,
      the molecular mechanism of this inhibition has remained unexplained. MATERIALS
      AND METHODS: We measured aggregation, changes in cytosolic Ca(2+) and tyrosine
      phosphorylation of the inhibitory receptor platelet endothelial cell adhesion
      molecule-1 (PECAM-1) in platelets stimulated with thrombin receptor (PAR-1)
      activating peptide (TRAP) and ADP and investigated the effects of alcohol-free
      polyphenolic grape extract (PGE), alcohol, and the polyphenols catechin, epi
      catechin, resveratrol, trans-resveratrol, and gallic acid. RESULTS: Polyphenolic
      grape extract induced dose-dependent inhibition of TRAP-induced and ADP-induced
      platelet aggregation and Ca(2+) mobilization. Inhibition was accompanied by
      activation of PECAM-1. Apart from a slight inhibition by catechin, ethanol or
      other individual polyphenols failed to inhibit aggregation or activate PECAM-1.
      CONCLUSIONS: Red wine inhibits platelet functions through its PGE content, which
      stimulates the inhibitory receptor PECAM-1, thereby attenuating platelet
      activation.

PMID- 17559546
TI  - Effect of ADH1B genotype on alcohol consumption in young Israeli Jews.
AB  - BACKGROUND: The alcohol dehydrogenase 1B (ADH1B) genotype affects the risk for
      alcoholism, with elevated prevalence of a protective allele in Jews. Alcohol
      consumption is increasing among younger Israeli Jews, reflecting environmental
      influences. We investigated whether the relationship of ADH1B genotype with
      alcohol consumption differed between younger and older adult Israelis. METHODS:
      Israeli community residents aged 22 to 65 participated in a structured interview
      that included questions on the maximum number of drinks on an occasion
      (Maxdrinks). The ADH1B genotype was determined for 68 participants and
      dichotomized into nonprotective (ADH1B(*)1/1) and protective (ADH1B(*)1/2 or
      ADH1B(*)2/2) genotypes. Using Maxdrinks as the dependent variable, Poisson's
      regression was used to test an age x genotype interaction. RESULTS: The ADH1B
      genotype interacted significantly with age (p=0.01) in a Poisson's model with
      Maxdrinks as the outcome. Among participants >or=33 years, Maxdrinks was low and
      unrelated to the ADH1B genotype. Among participants <33 years with ADH1B(*)1/2 or
      ADH1B(*)2/2, Maxdrinks was also low (mean, 2.6 drinks) but among those with
      ADH1B(*)1/1, Maxdrinks was substantially higher (mean, 6.2 drinks). CONCLUSION:
      Maximum lifetime drinking among younger adult Israelis without genetic protection
      exceeded thresholds for risky and unsafe drinking (>or=5 drinks). Environmental
      influences promoting greater drinking among younger Israelis may particularly
      affect those with the nonprotective, more common ADH1B genotype.

PMID- 17559547
TI  - Alcohol-induced disruption of endocrine signaling.
AB  - This article contains the proceedings of a symposium at the 2006 ISBRA meeting in
      Sydney Australia, organized and cochaired by Martin J. Ronis and Thomas M.
      Badger. The presentations were (1) Effect of long-term ethanol consumption on
      liver injury and repair, by Jack R. Wands; (2) Alcohol-induced insulin resistance
      in liver: potential roles in regulation of ADH expression, ethanol clearance, and
      alcoholic liver disease, by Thomas M. Badger; (3) Chronic gestational exposure to
      ethanol causes brain insulin and insulin-like growth factor resistance, by
      Suzanne M de la Monte; (4) Disruption of IGF-1 signaling in muscle: a mechanism
      underlying alcoholic myopathy, by Charles H. Lang; (5) The role of reduced plasma
      estradiol and impaired estrogen signaling in alcohol-induced bone loss, by Martin
      J. Ronis; and (6) Short-term influence of alcohol on appetite-regulating hormones
      in man, by Jan Calissendorff.

PMID- 17559548
TI  - Place conditioning in a two- or three-conditioning compartment apparatus: a
      comparative study with morphine and U-50,488.
AB  - We have comparatively studied the effects of two opioids in the rat place
      conditioning paradigm in identical experimental conditions (including double
      drug/saline conditioning daily sessions for 3 days), with the only exception of
      using either a two- or three-conditioning compartment apparatus. Morphine-induced
      place preference appeared to be similar with two- and three-conditioning
      compartments, but U-50,488-induced place aversion was consistently more prominent
      when a two-conditioning compartment apparatus was used. It is suggested that,
      when the results of conditioning are being tested, the presence of neutral
      environments decreases the sensitivity of the procedure to quantify place
      aversions.

PMID- 17559549
TI  - Prodynorphin gene promoter repeat associated with cocaine/alcohol codependence.
AB  - There is strong evidence for a genetic contribution to individual differences in
      vulnerability to drug addictions. Studies have shown that the 68-base pair repeat
      polymorphism in the promoter region of the human prodynorphin gene contains a
      putative AP-1 binding site, and that three or four repeat copies result in
      greater transcriptional activation. Here, we report on a separate cohort of 302
      subjects ascertained and characterized extensively by Diagnostic and Statistical
      Manual of Mental Disorders-Fourth Edition and Addiction Severity Index criteria
      as: (1) a control group of 127 subjects with no history of alcohol or drug abuse
      or dependence; (3) a case group of 82 with cocaine dependence only; and (3) a
      case group of 93 with cocaine and alcohol codependence. The promoter region of
      the prodynorphin gene containing the repeat was amplified from genomic DNA by
      polymerase chain reaction and analyzed via gel electrophoresis. Statistical tests
      were performed with data stratified by the three major ethnic groups studied:
      African American, Caucasian and Hispanic. For analyses, genotypes were grouped
      into short (1,1; 1,2; 2,2), short/long (1,3; 2,3; 1,4; 2,4) and long (3,3; 3,4;
      4,4) repeats. Deviation from Hardy-Weinberg Equilibrium in the African American
      control group necessitated testing for association using grouped genotypes rather
      than grouped alleles. In controls, a significant difference was found in grouped
      genotype distribution among ethnicities. We found a point-wise, but not
      experiment-wise across-ethnicities, significant difference in grouped genotype
      frequency between the cocaine/alcohol-codependent group and the controls in
      African Americans, with genotypes containing longer alleles found at higher
      frequency in the codependent group.

PMID- 17559550
TI  - Preliminary radiation hybrid map for river buffalo chromosome 6 and comparison to
      bovine chromosome 3.
AB  - We present the first radiation hybrid (RH) map of river buffalo (Bubalus bubalis)
      chromosome 6 (BBU6) developed with a recently constructed river buffalo whole
      genome RH panel (BBURH(5000)). The preliminary map contains 33 cattle-derived
      markers, including 12 microsatellites, 19 coding genes and two ESTs, distributed
      across two linkage groups. Retention frequencies for markers ranged from 14.4% to
      40.0%. Most of the marker orders within the linkage groups on BBU6 were
      consistent with the cattle genome sequence and RH maps. This preliminary RH map
      is the starting point for comparing gene order between river buffalo and cattle,
      presenting an opportunity for the examination of micro-rearrangements of these
      chromosomes. Also, resources for positional candidate cloning in river buffalo
      are enhanced.

PMID- 17559551
TI  - AFLP-based genetic linkage maps of the blue mussel (Mytilus edulis).
AB  - We report the construction of the first genetic linkage map in the blue mussel,
      Mytilus edulis. AFLP markers were used in 86 full-sib progeny from a controlled
      pair mating, applying a double pseudo-test cross strategy. Thirty-six primer
      pairs generated 2354 peaks, of which 791 (33.6%) were polymorphic in the mapping
      family. Among those, 341 segregated through the female parent, 296 through the
      male parent (type 1:1) and 154 through both parents (type 3:1). Chi-square
      goodness-of-fit tests revealed that 71% and 73% of type 1:1 and 3:1 markers
      respectively segregated according to Mendelian inheritance. Sex-specific linkage
      maps were built with mapmaker 3.0 software. The female framework map consisted of
      121 markers ordered into 14 linkage groups, spanning 862.8 cM, with an average
      marker spacing of 8.0 cM. The male framework map consisted of 116 markers ordered
      into 14 linkage groups, spanning 825.2 cM, with an average marker spacing of 8.09
      cM. Genome coverage was estimated to be 76.7% and 75.9% for the female and male
      framework maps respectively, rising to 85.8% (female) and 86.2% (male) when
      associated markers were included. Twelve probable homologous linkage group pairs
      were identified and a consensus map was built for nine of these homologous pairs
      based on multiple and parallel linkages of 3:1 markers, spanning 816 cM, with
      joinmap 4.0 software.

PMID- 17559552
TI  - Mapping quantitative trait loci for osteochondrosis in fetlock and hock joints
      and palmar/plantar osseus fragments in fetlock joints of South German Coldblood
      horses.
AB  - The aim of this study was to identify quantitative trait loci (QTL) for
      osteochondrosis (OC) and palmar/plantar osseous fragments (POF) in fetlock joints
      in a whole-genome scan of 219 South German Coldblood horses. Symptoms of OC and
      POF were checked by radiography in 117 South German Coldblood horses at a mean
      age of 17 months. The radiographic examination comprised the fetlock and hock
      joints of all limbs. The genome scan included 157 polymorphic microsatellite
      markers. All microsatellite markers were equally spaced over the 31 autosomes and
      the X chromosome, with an average distance of 17.7 cM and a mean polymorphism
      information content (PIC) of 63%. Sixteen chromosomes harbouring putative QTL
      regions were further investigated by genotyping the animals with 93 additional
      markers. QTL that had chromosome-wide significance by non-parametric Z-means and
      LOD scores were found on 10 chromosomes. This included seven QTL for fetlock OC
      and one QTL on ECA18 associated with hock OC and fetlock OC. Significant QTL for
      POF in fetlock joints were located on equine chromosomes 1, 4, 8, 12 and 18. This
      genome scan is an important step towards the identification of genes responsible
      for OC in horses.

PMID- 17559553
TI  - Identification of 10 882 porcine microsatellite sequences and virtual mapping of
      4528 of these sequences.
AB  - A total of 10 882 porcine microsatellite repeats were identified in genomic
      shotgun sequences from the Sino-Danish Pig Genome Sequencing Consortium
      (http://www.piggenome.dk). Of these, 4528 microsatellites were placed on a pig
      human comparative map by blast analysis of porcine sequences against the human
      genome (blast cut-off threshold =1 x 10(-5)). All microsatellite sequences placed
      on the comparative map are accessible at
      http://www.animalgenome.org/QTLdb/pig.html. These sequences increase the number
      of identified microsatellites in the porcine genome by several orders of
      magnitude. They are a new resource of microsatellite sequences for generating
      markers to be used in linkage studies and in fine mapping and positional cloning
      of quantitative trait loci.

PMID- 17559554
TI  - The g.243A>G mutation in intron 17 of MUC4 is significantly associated with
      susceptibility/resistance to ETEC F4ab/ac infection in pigs.
AB  - Using a porcine radiation hybrid panel, we assigned the mucin 4 (MUC4) gene to
      SSC13q41, which harbours the enterotoxigenic Escherichia coli (ETEC) F4ab/ac
      receptor locus. In addition, we identified two SNPs in intron 17 of MUC4
      (DQ124298:g.243A>G and DQ124298:g.334A>G) in the parental population of a White
      Duroc x Erhualian cross. Association analysis showed that the MUC4 g.243A>G
      mutation was strongly associated with ETEC F4ab/ac, and especially with F4ac
      adhesion phenotypes in the White Duroc x Erhualian resource population,
      indicating that this polymorphism was in a significant linkage disequlibrium with
      the ETEC F4ab/ac receptor locus. Because of different linkage disequlibrium
      values between the ETEC F4ab and F4ac adhesion phenotypes and the MUC4 g.243A>G
      mutation, we argue that the inheritance of F4ab and F4ac receptors might be under
      the control of two closely linked loci.

PMID- 17559555
TI  - A 12 000-rad whole-genome radiation hybrid panel in sheep: application to the
      study of the ovine chromosome 18 region containing a QTL for scrapie
      susceptibility.
AB  - Whole-genome radiation hybrid (RH) panels have been constructed for several
      species, including cattle. RH panels have proven to be an extremely powerful tool
      to construct high-density maps, which is an essential step in the identification
      of genes controlling important traits, and they can be used to establish high
      resolution comparative maps. Although bovine RH panels can be used with ovine
      markers to construct sheep RH maps based on bovine genome organization, only some
      (c. 50%) of the markers available in sheep can be successfully mapped in the
      bovine genome. So, with the development of genomics and genome sequencing
      projects, there is a need for a high-resolution RH panel in sheep to map ovine
      markers. Consequently, we have constructed a 12 000-rad ovine whole-genome RH
      panel. Two hundred and eight hybrid clones were produced, of which 90 were
      selected based on their retention frequency. The final panel had an average
      marker retention frequency of 31.8%. The resolution of this 12 000-rad panel
      (SheepRH) was estimated by constructing an RH framework map for a 23-Mb region of
      sheep chromosome 18 (OAR18) that contains a QTL for scrapie susceptibility.

PMID- 17559556
TI  - Absence of population substructuring in Zimbabwe chicken ecotypes inferred using
      microsatellite analysis.
AB  - The objective of this study was to investigate the population structure of
      village chickens found in the five agro-ecological zones of Zimbabwe. Twenty-nine
      microsatellites were genotyped for chickens randomly selected from 13
      populations, including the five eco-zones of Zimbabwe (n = 238), Malawi (n = 60),
      Sudan (n = 48) and six purebred lines (n = 180). A total of 280 alleles were
      observed in the 13 populations. Forty-eight of these alleles were unique to the
      Zimbabwe chicken ecotypes. The average number (+/-SD) of alleles/locus was 9.7 +/
      5.10. The overall heterozygote deficiency in the Zimbabwe chickens (F(IT) +/-
      SE) was 0.08 +/- 0.01, over 90% of which was due to within-ecotype deficit
      (F(IS)). Small Nei's standard genetic distances ranging from 0.02 to 0.05 were
      observed between Zimbabwe ecotypes compared with an average of 0.6 between
      purebred lines. The structure software program was used to cluster individuals to
      2 </= K </= 7 assumed clusters. The most probable clustering was found at K = 6.
      Ninety-seven of 100 structure runs were identical, in which Malawi, Sudan and
      purebred lines split out as independent clusters and the five Zimbabwe ecotypes
      clustered into one population. The within-ecotype marker-estimated kinships (mean
      = 0.13) differed only slightly from the between-ecotype estimates. Results from
      this study lead to a rejection of the hypothesis that village chickens are
      substructured across agro-ecological zones but indicated high genetic diversity
      within the Zimbabwe chicken population.

PMID- 17559557
TI  - Management of dry eye related to systemic diseases in childhood and longterm
      follow-up.
AB  - PURPOSE: Dry eye in children is not common in general practice and is usually
      referred to tertiary centres for diagnostic confirmation. In the present review
      we examine the potential causes of dry eye in children and report the management
      and longterm follow-up of dry eye in childhood with reference to clinical
      diversity, systemic associations, ocular outcomes and treatment trends. METHODS:
      A retrospective, consecutive case series was studied by evaluating the clinical
      charts of children with dry eye over a 96-month period. Minimal diagnostic
      inclusion criteria were presence of ocular surface damage and tear deficiency.
      RESULTS: Fourteen patients with an age range at presentation of 1-17 years were
      evaluated. Ten patients were female, four were male and all had bilateral
      involvement. The most frequent symptoms were red eye, photophobia and low visual
      acuity (VA). Four patients had corneal ulcers. Two patients had best corrected
      visual acuity (BCVA) < or = 20/200 at first examination. One of these plus
      another patient presented with BCVA < or = 20/200 at the last visit. All patients
      were treated with artificial tears; three received autologous serum tears and
      five submitted to conjunctival flaps to preserve the integrity of the eye.
      Associated systemic conditions were found in all patients and were congenital in
      six of them. CONCLUSIONS: Early manifestations of dry eye in childhood are a
      potential indication of systemic disease. The ocular condition may be
      misdiagnosed and correct treatment delayed. Most diseases are bilateral and may
      jeopardize VA. Systemic investigation, close follow-up and preparing the family
      for longterm and multidisciplinary treatment are necessary to preserve ocular
      health and identify systemic associations.

PMID- 17559558
TI  - Pneumatic displacement and intravitreal bevacizumab in the management of
      subretinal haemorrhage caused by choroidal neovascularization.

PMID- 17559559
TI  - Regional differences in the functional and biochemical properties of endothelin
      receptor subtypes in the rabbit prostatic urethra.
AB  - OBJECTIVE: To examine the regional differences in the functional
      (pharmacological) and biochemical properties of endothelin (ET) receptors in the
      rabbit prostatic urethra. MATERIALS AND METHODS: The properties of ET receptors
      in 6-month-old male rabbit prostatic urethras were examined using isolated muscle
      bath and radioligand receptor-binding techniques. Using plasma membrane
      suspensions, saturation and inhibition experiments with [(125)I]ET-1 and
      unlabelled agonists and antagonists (ET(A)-selective antagonist BQ123, and ET(B)
      selective agonist sarafotoxin 6c, STX6c) were done to determine the ET receptor
      densities and their subtype specificities in the different regions of the
      urethra. RESULTS: The ETs (ET-1 and ET-3) produced significant concentration
      dependent contractile responses in the smooth muscle strips from the different
      regions of the urethra. Although the maximum contractile responses induced by ET
      1 were similar in the different regions, the maximum contractile responses
      induced by ET-3 were greater in the distal region than in the proximal or middle
      regions, suggesting that the contractile response to ET-1 is more potent than
      that to ET-3 in all regions, and that there are region-specific differences in
      the responses to ET-3 but not ET-1. Moreover, the ET-3-induced contractile
      response was suppressed by BQ788 (a selective antagonist of the ET(B) receptor)
      suggesting that the ET(B) receptor subtype contributes to the contractile
      responses mediated by ET-3. The ET receptors were expressed in higher
      concentrations in the distal than in the proximal or middle regions. BQ123 and
      STX6c inhibited [(125)I]ET-1 binding in all regions with high and low affinity
      constants, indicating the presence of both ET(A) and ET(B) receptor subtypes. The
      proportions of high-affinity binding sites for BQ123, representing ET(A)
      receptors, were approximately 68%, 63% and 42% in the proximal, middle and distal
      regions, respectively. By contrast, the proportions of high-affinity binding
      sites for STX6c, representing ET(B) receptors, were approximately 27%, 35% and
      52% in the proximal, middle, and distal regions, respectively. These data
      indicate the presence of regional differences in the densities and subtype
      specificities of ET receptor subtypes, and the existence of regional differences
      in the rabbit prostatic urethra. CONCLUSION: The results suggest regional
      differences in ET(B) receptor subtypes that mediate contractile responses to ET
      3, reflecting differences in the densities and specificities of the ET receptor
      subtypes in the rabbit prostatic urethra.

PMID- 17559560
TI  - Progression after docetaxel-based chemotherapy in androgen-independent prostate
      cancer.
AB  - OBJECTIVE: To assess the clinical pattern of progression and prostate-specific
      antigen doubling time (PSA-DT) after exposure to docetaxel-based chemotherapy in
      patients with androgen-independent prostate cancer (AIPC). PATIENTS AND METHODS:
      Fifty-five patients received docetaxel-based chemotherapy; data were collected
      retrospectively from three different departments. Progression was known in 44
      (79%) and the PSA-DT was available in 33 patients. RESULTS: Of the 29 patients
      with soft-tissue and soft-tissue plus bone metastases, 22 (76%) developed soft
      tissue progression. Among the 35 patients with bone and bone plus soft-tissue
      metastases, 27 (77%) had osseous progression. There was no difference between the
      PSA-DT at progression before and after docetaxel-based therapy (mean 3.1 vs 2.7
      months, P = 0.592, Student's t-test.). However, the median (range) PSA-DT at
      progression after docetaxel-based therapy was 0.84 (0.3-4) months in patients
      with a PSA response, significantly shorter than the median of 3.1 (0.3-12) months
      of patients with no biochemical response (P = 0.002, Student's t-test). The PSA
      DT dynamics at progression had no effect on survival (P = 0.63, log-rank test).
      CONCLUSION: The pattern of progression after docetaxel-based chemotherapy is
      predominantly osseous in patient with bone metastases and mostly soft-tissue in
      those with soft-tissue disease. Progression after docetaxel-based chemotherapy in
      AIPC does not modify the PSA-DT before docetaxel. Evaluation of a larger
      population is needed to assess the clinical relevance of PSA dynamics after
      docetaxel therapy.

PMID- 17559561
TI  - The case for modifying the Gleason grading system.

PMID- 17559563
TI  - Gland volume in the assessment of prostatic disease: does size matter?

PMID- 17559562
TI  - Increased testicular 8-hydroxy-2'-deoxyguanosine in patients with varicocele.
AB  - OBJECTIVES: To assess immunohistochemically 8-hydroxy-2'-deoxyguanosine (8-OHdG,
      a sensitive biological marker of oxidative damage and stress) in testicular
      tissue from patients with varicocele, to determine whether 8-OHdG is related to
      spermatogenesis, as oxidative stress in testicular DNA is associated with poor
      semen quality and reduced fertility. PATIENTS, SUBJECTS AND METHODS: Testicular
      tissue samples were collected from the testes of 36 patients with varicocele and
      five normal volunteers. The mean (sd) age of the patients was 35.3 (5.4) years.
      The prevalence of immunostained germ cells among all the germ cells in >20
      seminiferous tubules was calculated. RESULTS: The mean (sd) sperm concentration
      and Johnsen's score in the varicocele group was lower than in the normal group,
      at 27.6 (11.8) vs 80.4 (21.7) million/mL (P < 0.001) and 7.6 (1.1) vs 9.0 (0.7),
      respectively (P < 0.05). In all patients, 8-OHdG was mainly expressed in the
      spermatogonia and spermatocytes in the seminiferous tubule. Immunostained germ
      cells correlated negatively with sperm concentration (r = -0.48, P = 0.01) and
      Johnsen's score (r = -0.46, P = 0.02), but not with follicle-stimulating hormone,
      luteinizing hormone or testosterone level. Immunostained germ cells were
      significantly more prevalent in the varicocele group, at 53.6 (5.7)%, than that
      in the normal group, at 14.3 (2.3)% (P < 0.001). The prevalence of immunostained
      germ cells and clinical grades were positively related; the ratio recorded for
      varicocele grades I, II and III was 38.0 (10.0)%, 41.0 (9.1)%, and 57.0 (9.3)%,
      respectively (grade I vs grade III, P < 0.05). CONCLUSIONS: Increased 8-OHdG
      expression in the testis was associated with deficient spermatogenesis in
      infertile men with varicocele.

PMID- 17559564
TI  - Liquid-based endometrial cytology: cyto-histological correlation in a population
      of 917 women.
AB  - OBJECTIVE: Liquid-based cytology, because of its capacity to reduce the obscuring
      factors and to provide thin-layer specimens, represents an opportunity to
      reevaluate endometrial cytology. In order to assess the utility of the liquid
      based method in endometrial diagnosis, we evaluated its accuracy in comparison
      with histology. METHODS: Nine hundred and seventeen women scheduled for
      hysteroscopy were enrolled in the study. After providing informed consent, all
      the women proceeded sequentially to hysteroscopy, endometrial cytology and then
      biopsy endometrial sampling. RESULTS: Cyto-histological correlations were
      possible in 519 cases (57%): in 361 (39%) cases the biopsy was inadequate, in 15
      (2%) the cytology was inadequate, and in 22 (2%) both were inadequate. At biopsy
      25 (3%) women had adenocarcinoma, 5 (1%) had adenomatous atypical hyperplasia and
      21 (2%) had simple non atypical hyperplasia. At cytology two adenocarcinomas and
      one adenomatous atypical hyperplasia were underrated as atypical hyperplasias and
      as non-atypical hyperplasia; two simple non-atypical hyperplasias were reported
      as negative; and eight cases were false positive (non-atypical hyperplasia at
      cytology, negative at biopsy). In our population, the cytology provided
      sufficient material more often than biopsy (P < 0.04). Sensitivity was estimated
      at 96%, specificity at 98%, positive predictive value at 86% and negative
      predictive value at 99%. CONCLUSIONS: We concluded that endometrial cytology may
      be an efficient diagnostic method. It could be applied to selected patients
      solely or in association with ultrasonography. The combination of these two
      noninvasive procedures may improve their diagnostic accuracy and reduce
      unnecessary hysteroscopies, thereby producing benefits for women and society.

PMID- 17559565
TI  - The complex cytological features of synovial sarcoma in fine needle aspirates, an
      analysis of four illustrative cases.
AB  - OBJECTIVE: The cytological features of conventional monophasic spindle cell and
      biphasic synovial sarcoma have been defined in detail in several large series.
      The cytology of rare morphological variants, especially the subtypes of poorly
      differentiated synovial sarcoma, are insufficiently evaluated and diagnostically
      difficult to define. The objective of the present study was to call attention to
      the variable cytology of rare variants of synovial sarcoma. Furthermore,
      adjunctive diagnostic methods, necessary for a correct diagnosis, are discussed.
      METHODS: Aspirates from four synovial sarcomas, with cytological features, which
      differed from those of conventional synovial sarcoma and from each other, were
      retrieved from our files and re-evaluated. RESULTS: In three of the cases a
      correct diagnosis was not obtained from routinely stained aspirates. In the
      fourth case, the correct diagnosis was established by a combination of
      cytomorphology, immunocytochemistry and fluorescence in situ hybridization (FISH)
      performed on the aspirated material. CONCLUSION: Ancillary diagnostic methods are
      necessary in the examination of aspiration smears from synovial sarcoma,
      especially of morphological variants with a cytomorphology that differs from
      conventional spindle-cell monophasic and biphasic tumours. Immunocytochemistry
      and molecular genetic examinations (reverse transcriptase polymerase chain
      reaction or FISH) are the methods of choice.

PMID- 17559566
TI  - Endoscopic ultrasound-guided fine needle aspiration cytology of the pancreas: a
      morphological and multimodal approach to the diagnosis of solid and cystic mass
      lesions.
AB  - Cytological evaluation of pancreatic masses and cysts is the preferred pre
      operative diagnostic modality and is increasingly being performed by endoscopic
      ultrasound. This review focuses on the multimodal approach at the Massachusetts
      General Hospital that utilizes clinical, cytological, radiological and ancillary
      studies in rendering a final cytological diagnosis.

PMID- 17559567
TI  - Fine needle aspiration of an axillary lymph node in a patient suspected of having
      metastatic cancer of unknown primary.

PMID- 17559568
TI  - Endoscopic ultrasonography-guided fine needle aspiration of a nodule in the
      rectovaginal septum.

PMID- 17559569
TI  - Analysis of initial slow waves (ISWs) at the seizure onset in patients with drug
      resistant temporal lobe epilepsy.
AB  - RATIONALE: The goal of this study is to analyze initial slow waves (ISWs) at
      seizure onset in patients with refractory temporal lobe epilepsy. ISWs are a
      specific type of ictal EEG pattern characterized by a slow wave at the seizure
      onset followed by low voltage fast activity. METHODS: Investigations were carried
      out on 14 patients from the UCLA hospital (USA) and 10 from the Ghent University
      Hospital (Belgium) implanted with depth and grid electrodes for localization of
      the epileptogenic zone. RESULTS: Sixty-one seizures in the UCLA group and 30
      seizures in the Ghent group were analyzed. Fourteen UCLA and seven Ghent patients
      had ISWs at seizure onset. The duration of ISWs varied between 0.3 to 6.0 s and
      maximum amplitude varied from 0.2 to 1.4 mV. ISWs in three of 14 UCLA patients
      (30% of seizures) had a consistent positive polarity at the deepest contacts that
      were located in the amygdala, hippocampus, or entorhinal cortex and reversed
      polarity outside of these brain areas (ISWs1). ISWs in 11 of 14 UCLA patients
      (70% of seizures) had negative polarity at the deepest electrodes and their
      amplitude increased toward the recording contacts located in the white matter or
      neocortex (ISWs2). All ISWs from the seven Ghent patients were negative in the
      depth contacts (ISWs2) and positive on grid electrodes at the cortical surface.
      ISWs1 were associated with EEG spikes at the onset and on increase in amplitude
      of 10-20 Hz sinusoidal activity. In contrast, ISWs2 were associated with
      suppression of EEG amplitude, an increase in frequency in the range of 20-50 Hz,
      and did not have EEG spikes at the onset. Multiunit neuronal activity showed
      strong synchronization of neuronal discharges during interictal spikes, but
      multiunit synchronization was not obvious during ISWs2. CONCLUSION: The existence
      of EEG spikes and phase reversal with ISWs1 indicates this type of seizure may be
      triggered by hypersynchronous neuronal discharges; however, seizures with ISWs2
      at the onset may be triggered by different mechanisms, perhaps nonneuronal.

PMID- 17559570
TI  - Impact of idiopathic epilepsy on mothers and fathers: strain, burden of care,
      worries and perception of vulnerability.
AB  - The purpose of the study was to examine the impact of idiopathic epilepsy on
      mothers and fathers in terms of strain, burden of care, worries and perception of
      vulnerability. Data were collected and analyzed shortly after the diagnosis (T0)
      and 12 months later (T1). The results indicated that at T0 parents of children
      with epilepsy showed higher levels of worries and perception of vulnerability
      than controls; mothers sustained a greater burden of care and exhibited higher
      levels of strain than fathers. At T1, strain and perception of vulnerability
      decreased both for mothers and fathers, while burden of care and worries remained
      stable. At T0 and T1, strain was associated with parents' perception of
      vulnerability and anxiety for their children's future.

PMID- 17559572
TI  - mRNA cycling sequence binding protein from Leishmania donovani (LdCSBP) is
      covalently modified by ubiquitination.
AB  - The lack of transcriptional regulation in trypanosomatids suggests the presence
      of distinct posttranscriptional mechanisms to control differential gene
      expression. In fact, the stability of S-phase specific mRNAs in these parasites
      is determined primarily by the presence of the octanucleotide sequence
      (C/A)AUAGAA(G/A) in the UTRs of the transcripts. Here, the characterization of
      LdCSBP is reported, which specifically binds to the octanucleotide containing
      RNA. The LdCSBP protein contains multiple putative functional domains, including
      two types of ubiquitin binding domains (UBA and CUE), two CCCH-type Zn-finger
      motifs probably responsible for specific RNA binding activity and a speculative
      endonuclease domain SMR. Interestingly, the protein is covalently modified
      through ubiquitination. This observation and the occurrence of multiple ubiquitin
      binding domains in the protein raise the possibility of regulation of the
      activity of LdCSBP by ubiquitination.

PMID- 17559571
TI  - In vivo EPR estimation of bilateral hippocampal antioxidant ability of rats with
      epileptogenesis induced by amygdalar FeCl3 microinjection.
AB  - PURPOSE: To measure the neural antioxidant function in the hippocampus of rats
      with epileptogenesis induced by microinjection of FeCl3 into the amygdala using
      the decay rate of the nitroxide radical as estimated by L-band electron
      paramagnetic resonance (EPR) spectroscopy. MATERIALS AND METHODS: Region-selected
      intensity determination (RSID) was used for the estimation of the nitroxide decay
      ratio. It is possible to estimate the in vivo hippocampal antioxidant ability
      using the half-life of the EPR signal of the blood-brain barrier-permeable
      nitroxide radical. Rats were microinjected with aqueous FeCl3 into the right
      amygdaloid body. Recording from chronically implanted depth electrodes showed the
      development of spike discharges with recurrent seizures arising from amygdalar
      regions with propagation into both hippocampi. Rats with unilateral aqueous FeCl3
      lesions were injected systemically with the nitroxide radical and then had EPR
      for RSID estimation at 5, 15, and 30 days after the iron salt injection. RESULTS:
      The in vivo antioxidant ability of the dorsal hippocampus was significantly
      decreased bilaterally in animals with FeCl3-induced seizures when compared to the
      control. CONCLUSION: Neural antioxidant function in the hippocampi of rats with
      chronic seizures induced by amygdalar FeCl3 was decreased early and both
      ipsilaterally and bilaterally.

PMID- 17559573
TI  - Glyceraldehyde-3-phosphate ferredoxin oxidoreductase (GAPOR) and
      nonphosphorylating glyceraldehyde-3-phosphate dehydrogenase (GAPN), key enzymes
      of the respective modified Embden-Meyerhof pathways in the hyperthermophilic
      crenarchaeota Pyrobaculum aerophilum and Aeropyrum pernix.
AB  - The growth of Pyrobaculum aerophilum on yeast extract and nitrate was stimulated
      by the addition of maltose. Extracts of maltose/yeast extract/nitrate-grown cells
      contained all enzyme activities of a modified Embden-Meyerhof (EM) pathway,
      including ATP-dependent glucokinase, phosphoglucose isomerase, ATP-dependent 6
      phosphofructokinase, fructose-1,6-phosphate aldolase, triose-phosphate isomerase,
      GAPOR, phosphoglycerate mutase, enolase and pyruvate kinase. The activity of
      GAPOR was stimulated about fourfold by maltose, indicating a role in sugar
      degradation. GAPOR was purified 200-fold to homogeneity and characterized as a 67
      kDa monomeric, extremely thermostable protein. The enzyme showed high specificity
      for glyceraldehyde-3-phosphate and did not use glyceraldehyde, acetaldehyde or
      formaldehyde as substrates. By matrix-assisted laser desorption/ionization-time
      of flight analysis of the purified enzyme, ORF PA1029 was identified as a coding
      gene, gapor, in the sequenced genome of Pyrobaculum aerophilum. The data indicate
      that the (micro)aerophilic Pyrobaculum aerophilum contains a functional GAPOR as
      part of a modified EM pathway. Cells of the strictly aerobic crenarchaeon
      Aeropyrum pernix also contain enzyme activities of a modified EM pathway similar
      to that of Pyrobaculum aerophilum, except that a GAPN activity replaces GAPOR
      activity.

PMID- 17559574
TI  - Mutations of the RAG3 gene encoding a regulator of fermentation in Kluyveromyces
      lactis are suppressed by a mutation of the transcription factor gene KlGCR1.
AB  - In Kluyveromyces lactis, Rag3 regulates both fermentative metabolism and thiamine
      biosynthesis. Regulation of fermentation is exerted at the level of transcription
      of KlPDC1. We have isolated and identified a mutation of the transcription factor
      KlGCR1, Klgcr1-1, which suppressed the fermentative-deficient phenotype
      associated with the RAG3 deletion. In the mutant, the transcription of KlPDC1 was
      restored. However, we found that the suppression was not specific to the RAG3
      mutation, as the Klgcr1-1 mutation could also suppress the fermentative defect
      associated with mutation of Sck1, another regulator of glycolysis.

PMID- 17559575
TI  - Th2-mediated anti-tumour immunity: friend or foe?
AB  - The concept that the immune system can recognise tumour cells and either
      eliminate them (tumour immune surveillance) or select for immunologically
      resistant variants (immunoediting) is gaining general acceptance by
      immunologists. In terms of an adaptive immune response to cancer, however, much
      of the research has focused on the response of cytotoxic CD8+ T lymphocytes to
      tumour-specific antigens and the production of Th1 cytokines by CD4+ and CD8+ T
      cells. In contrast, Th2-mediated immunity has traditionally been viewed as
      favouring tumour growth, both by promoting angiogenesis and by inhibiting cell
      mediated immunity and subsequent tumour cell killing. While there is evidence
      that components of type 2 inflammation, such as B cells and interleukin-10, do
      promote tumour growth, there are also many studies demonstrating the anti-tumour
      activity of CD4+ Th2 cells, particularly in collaboration with tumour
      infiltrating granulocytes, such as eosinophils. In this review, we examine all
      the components of type 2 immunity and their effects on tumour growth.
      Collectively, from this analysis, we conclude that there is a great potential for
      the development of Th2-mediated immunotherapies that harness the cytotoxic
      activity of eosinophils.

PMID- 17559576
TI  - Interleukin-10 gene promoter polymorphisms and the risk of nasopharyngeal
      carcinoma.
AB  - Genetic factors are known to be important in the development of nasopharyngeal
      carcinoma (NPC). Interleukin-10 (IL-10) is an immunosuppressive cytokine which
      may facilitate development of cancer by supporting tumor escape from the immune
      response. Interindividual variations in IL-10 production were genetically
      contributed to polymorphisms within IL-10 promoter region. The aim of this study
      was to determine whether single nucleotide polymorphisms (SNPs) at positions 
      1082 (A/G), -819 (T/C) and -592 (A/C) in the IL-10 gene promoter were involved in
      predisposing an individual to NPC. One hundred and ninety-eight patients with NPC
      and 210 age- and sex-matched controls, genotypes were determined using polymerase
      chain reaction-restriction fragment length polymorphism. There were significantly
      differences in the genotype and allele distribution of -1082 A/G polymorphism of
      the IL-10 gene among cases and controls. The -1082 AG and GG genotypes were
      associated with a significantly increased risk of NPC as compared with the -1082
      AA genotypes. Haplotype analysis showed that the homozygosity of the GCC
      haplotype (defined by SNPs at positions -1082, -819 and -592) of IL-10 gene
      conveys the highest risk for NPC compared with the homozygosity for the ATA
      haplotype. This study shows for the first time an association between IL-10 gene
      promoter -1082 A/G polymorphism and its haplotype may contribute to genetic
      susceptibility to NPC in a Chinese population.

PMID- 17559577
TI  - HLA class II amino acid epitopes as susceptibility markers of sarcoidosis.
AB  - Sarcoidosis is a multisystemic disorder of unknown etiology, affecting primarily
      the lung and characterized by epithelioid granulomas. Disease association studies
      showed human leukocyte antigen (HLA) class II to be related to sarcoidosis.
      Initially, we studied the association of sarcoidosis with DQB1, and in the
      present study, we evaluated all amino acid variants of the HLA-DPB1, -DQB1, 
      DRB1, -DRB3, -DRB4 and -DRB5 genes to identify possible polymorphisms associated
      with the disease. Patients and controls were typed for class II genes to the
      allele level by sequence-based typing. Multiple logistic regression models showed
      DRAla71 and DQPhe9 to be independently associated with the disease. Subdivision
      of patients according to their radiographic stage resulted in identification of
      DRArg74 as independent associated residue in the RS I group, whereas DRAla71 and
      DQTyr30 were associated with RS II-IV groups. Polymorphic residues specifically
      associated with sarcoidosis shed new light on the characteristics of sarcoidosis
      triggered peptides. Overall, pocket 9 of DQ and pocket 4 of DR seem to be the
      most important areas involved in the association with sarcoidosis.

PMID- 17559578
TI  - Macrophage migration inhibitory factor gene influences the risk of developing
      tuberculosis in northwestern Colombian population.
AB  - Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine that
      regulates innate and adaptative immunity responses against pathogens. The MIF
      gene, at 22q11.2, is polymorphic. Functional promoter variants in the MIF gene
      influence susceptibility to inflammatory diseases in Caucasians and Africans. An
      association study was carried out to examine the influence of MIF-173 single
      nucleotide polymorphism and the MIF-794 microsatellite on the susceptibility to
      develop human tuberculosis (TB) in a well-defined Latin-American population. To
      this purpose, 230 northwestern Colombian patients with pulmonary TB, negative for
      human immunodeficiency virus infection, and 235 matched healthy individuals
      stratified by the tuberculin skin test were examined. Multivariate analysis
      showed that MIF-173C allele was associated with disease (odds ratio = 1.64, 95%
      confidence interval 1.07-2.52) in a dominant pattern. No allele in the MIF-794
      CATT microsatellite was associated with risk of TB. These results indicate that
      MIF gene influences the risk of developing TB in the studied population.

PMID- 17559579
TI  - Influence of KIR gene diversity on the course of HSV-1 infection: resistance to
      the disease is associated with the absence of KIR2DL2 and KIR2DS2.
AB  - Herpes simplex virus type 1 (HSV-1) causes lifelong latent infections in most
      humans. Periodical virus reactivations from latency in the neurons of sensitive
      ganglia lead to transport to mucocutaneous regions and productive replication,
      which results in recurrent inflammatory herpetic lesions or in asymptomatic virus
      shedding. The medical consequences of such lesions and the frequency of
      recurrences vary greatly in different subjects. Furthermore, many infected
      individuals never suffer manifestations of the disease, even when exposed to
      stimuli that trigger clinical recurrences in other humans. The origin of the
      variability in the clinical course of HSV-1 infection remains unexplained.
      Herpesviruses and other pathogens sabotage the expression of major
      histocompatibility complex class I molecules by infected cells, thus subverting T
      cell-mediated immunity. Subversion of antigen presentation is counteracted by
      natural killer cells, which survey the human leukocyte antigen (HLA) expression
      by specific receptors. These include the killer cell immunoglobulin-like
      receptors (KIRs), which are encoded by a complex of extremely diverse and rapidly
      evolving genes. Here, we analyze the contribution of KIR gene diversity to the
      variable clinical course of HSV-1 infection by comparing the distribution of
      these genes in humans with clinical manifestations of the disease with that in
      asymptomatically infected donors. This study provides preliminary evidence that
      the receptors KIR2DL2 and KIR2DS2 predispose to symptomatic HSV-1 infection and
      favor the frequently recurring forms of the disease. Possible contribution of the
      'HLA-C1' ligand to HSV-1 disease was not statistically supported. Because of an
      absolute genetic linkage between KIR2DL2 and KIR2DS2, we could not determine
      which receptor was primarily responsible for the observed association, but our
      results suggest that presence in the genome of KIR2DL2 and KIR2DS2 hinders an
      effective cellular response to HSV-1.

PMID- 17559580
TI  - Extraordinary cross-reactivity of an autoimmune T-cell receptor recognizing
      specific peptides both on autologous and on allogeneic HLA class II molecules.
AB  - A T-cell receptor's (TCR) recognition of a human leukocyte antigen (HLA)-peptide
      complex (pHLA) is normally described as being restricted by the HLA molecule and
      specific for the peptide. This is, however, not always true. Several TCRs have
      been described, which cross-react with other peptides bound to the restricting
      HLA molecule. This phenomenon has been considered a variant of molecular mimicry
      and is suggested to be one of the mechanisms behind autoimmunity. The positive
      selection of T cells in the thymus imposes low-affinity recognition of the TCRs
      toward self-pHLA, which increases the probability of the TCR to be promiscuous by
      nature, and further implies that the T-cell repertoire contains TCRs prone to be
      autoreactive and thus able to induce autoimmunity. We present an autoimmune TCR
      showing extreme cross-reactivity to several pHLA comprising both own HLA class II
      restriction element and allogeneic HLA class II restriction elements in complex
      with both self-derived and microbially derived peptides. The existence of such a
      significant cross-reactivity in the context of distinct HLA-DR molecules might be
      more common among autoimmune TCRs than previously anticipated and potentially
      reveals a new way of designing altered peptide ligands for therapeutic use.

PMID- 17559581
TI  - An improved method for dog leukocyte antigen 88 typing and two new major
      histocompatibility complex class I alleles, DLA-88*01101 and DLA-88*01201.
AB  - Development of preclinical dog models of solid organ and hematopoietic
      transplantation is critically dependent upon characterization of the polymorphic
      major histocompatibility complex class I and class II loci. While the class II
      alleles are easily typed as the polymorphic positions reside on a single exon,
      typing the class I locus is tedious. We have improved the class I typing method
      by designing improved primers and adopting alternative DNA amplification and
      cloning reagents that circumvent the use of radioactivity and the need for the
      single-stranded conformation polymorphism gels. The method is reliable in typing
      dogs for the class I dog leukocyte antigen (DLA)-88 locus, and through its use,
      we describe here two new alleles DLA-88*01101 and DLA-88*01201.

PMID- 17559582
TI  - HLA-B*5701 typing: evaluation of an allele-specific polymerase chain reaction
      melting assay.
AB  - Inheritance of HLA-B*5701 is a strong predictor of a hypersensitivity reaction to
      the anti-HIV drug abacavir. The identification of susceptible individuals prior
      to the institution of abacavir therapy is therefore of clinical importance and
      has generated demand for a simple and rapid diagnostic test for carriage of HLA
      B*5701. In this study, we describe the development of such a method based on
      allele-specific polymerase chain reaction (AS-PCR) and melting curve analysis.
      Ninety-six patient samples including 36 HLA-B*5701-positive samples and 60 HLA
      B*5701-negative samples were analysed. Compared with sequence-based typing, this
      method had 100% sensitivity and specificity for the HLA-B*5701 allele. In
      conclusion, the AS-PCR/melting curve approach minimises post-polymerase chain
      reaction handling processing and provides an attractive alternative to currently
      described AS-PCR methods.

PMID- 17559583
TI  - HLA-G alleles and HLA-G 14 bp polymorphisms in a Brazilian population.
AB  - Brazilians represent one of the most heterogeneous populations in the world as
      the result of five centuries of interethnic crosses. We investigated the
      polymorphism of the HLA-G locus in a Brazilian urban sample. HLA-G alleles were
      determined by SBT analysis of exons 2-4 and 8 in 103 unrelated individuals. The
      genotyping analysis identified 11 different HLA-G alleles, including the recently
      described G*010110 allele, and four new variants in this population. These data
      indicate that this Brazilian population presents high HLA-G allelic polymorphism,
      suggesting increased levels of intrapopulational genetic diversity that may be
      because of the admixed nature of the sample. This is the first study regarding
      HLA-G genotyping that was performed at such refined resolution level in this
      heterogeneous population.

PMID- 17559584
TI  - A novel HLA-A*33 (A*3309) allele in a Caucasian family that differs at protein
      position 66 from HLA-A*3308.
AB  - A novel human leucocyte antigen (HLA)-A33 (HLA-A*3309) allele has been identified
      in a Caucasian family from Middle Europe using single allele-specific sequencing
      strategy. This allele is identical to the HLA-B*3308 allele except for one point
      mutation in exon 2 at codon 66 (AAA-->AAT), resulting in an amino acid change
      from lysine (K) to asparagine (N).

PMID- 17559585
TI  - Sequence analysis of the novel allele HLA-A*110106 in the Chinese population.
AB  - A novel HLA-A*110106 allele was identified in the Chinese individual by
      polymerase chain reaction sequence-based typing.

PMID- 17559586
TI  - Haplotype-specific amplification and nucleotide sequencing reveal the novel
      allele HLA-B*080104.
AB  - The novel allele human leukocyte antigen (HLA)-B*080104 differs from HLA-B*080101
      by a synonymous nucleotide exchange at position 231 in exon 2 (C-->T).

PMID- 17559587
TI  - A novel HLA-B*35 (B*3570) allele of a Caucasian family differing with one amino
      acid mismatch from HLA-B*3503 allele in exon 4.
AB  - A novel human leucocyte antigen (HLA)-B35 (HLA-B*3570) allele has been identified
      in a Caucasian family from Middle Europe using single allele-specific sequencing
      strategy. This allele is identical to the HLA-B*3503 allele except for one point
      mutation in exon 4 at codon 188 (CAC-->CGC), resulting in an amino acid change
      from histidine to arginine.

PMID- 17559588
TI  - HLA-DQB1*0319, a novel HLA-DQB1 allele, shows strong haplotype association to HLA
      DRB1*1102.
AB  - The new human leukocyte antigen-DQB1*0319 allele was identified in a prospective
      bone marrow donor by sequence-based typing. This novel allele differs from the
      DQB1*0301 allele at nucleotide position 554 (C-->T), which results in a Thr to
      Ile amino acid exchange. The new allele shows a strong association to DRB1*1102,
      suggesting that the haplotype DRB1*1102-DQB1*0319 is quite common.

PMID- 17559589
TI  - Characterization of a new HLA-DRB1*1405 variant, HLA-DRB1*140503, identified by
      sequence-based typing.
AB  - A new human leukocyte antigen-DRB1*140503 differs from DRB1*140501 with T to C
      transition at codon 78 (TAT-->TAC) of exon 2 without coding change.

PMID- 17559590
TI  - A novel DRB1*04 allele.
AB  - Discovery of the novel DRB1*0464 allele is described. This allele contains a
      nucleotide substitution in codon 13 that changes the amino acid histidine coded
      for in all other DRB1*04 alleles to tyrosine. This allele was found in a parent
      and one child of a North American Caucasian family with the haplotype: A*03,
      B*07, DRB1*0464, DRB4*0103, DQB1*0301.

PMID- 17559591
TI  - Identification of four novel MHC-C alleles in chimpanzees.
AB  - Sequence-based typing strategy is used to identify polymorphism of Patr-C. Four
      new Patr-C alleles are described.

PMID- 17559592
TI  - Nomenclature for factors of the HLA system, update February 2007.

PMID- 17559593
TI  - Nomenclature for factors of the HLA system, update March 2007.

PMID- 17559594
TI  - Towards innovative international classification and diagnostic systems: ICD-11
      and person-centered integrative diagnosis.

PMID- 17559595
TI  - Schizophrenia trials in China: a survey.
AB  - OBJECTIVE: China's biomedical research activity is increasing and this literature
      is becoming more accessible online. Our aim was to survey all randomized control
      schizophrenia trials (RCTs) in one Chinese bibliographic database. METHOD:
      Chinese Academic Journals was electronically searched for RCTs and all relevant
      citations were also sought on PubMed to ascertain global accessibility. RESULTS:
      The search identified 3275 records, of which 982 were RCTs relevant to
      schizophrenia. A total of 71% (699) could be found by using English phrases. All
      the main body of text of the 982 papers was in Mandarin. On average, these trials
      involved about 100 people, with interventions and outcome measures familiar to
      schizophrenia trialists worldwide. Four of the 982 records (<1%) were identified
      on PubMed. CONCLUSION: Those undertaking systematic reviews should search the
      Chinese literature for relevant material. Failing to do this will leave the
      results of systematic reviews prone to random error or bias, or both.

PMID- 17559596
TI  - Delay in initial treatment contact after first onset of mental disorders in
      metropolitan China.
AB  - OBJECTIVE: There has been no community-based research on treatment delay among
      people with mental disorders in China. This study examines lifetime treatment and
      treatment delay in metropolitan China. METHOD: A multi-stage probability survey
      of 5201 respondents was administered in Beijing and Shanghai. Age of first
      treatment contact after onset of each of the three lifetime DSM-IV/CIDI disorder
      classes was compared with retrospective information on age of disorder onset.
      Length and predictors of treatment delay were examined using survival analysis.
      RESULTS: Survival curves estimate that 44.7%, 25.7%, and 7.9% of people with
      anxiety, substance, and mood disorders, respectively, will ever make treatment
      contact. Delays in first treatment contact of anxiety (21 years) and substance
      (17 years) disorders are longer than that of mood disorders (1 year). These
      delays are largely unrelated to sociodemographic variables. CONCLUSION: Failure
      to receive treatment is a pervasive phenomenon among people with mental disorders
      in metropolitan China.

PMID- 17559597
TI  - Electrophysiological subtypes of psychotic states.
AB  - OBJECTIVE: This research sought neurobiological features common to psychotic
      states displayed by patients with different clinical diagnoses. METHOD: Cluster
      analysis with quantitative electroencephalographic (QEEG) variables was used to
      subtype drug-naive, non-medicated, and medicated schizophrenic, depressed and
      alcoholic patients with psychotic symptoms, from the USA and Germany. QEEG source
      localization brain images were computed for each cluster. RESULTS: Psychotic
      patients with schizophrenia, depression and alcoholism, and drug- naive
      schizophrenic patients, were distributed among six clusters. QEEG images revealed
      one set of brain regions differentially upregulated in each cluster and another
      group of structures downregulated in the same way in every cluster. CONCLUSION:
      Subtypes previously found among 94 schizophrenic patients were replicated in a
      sample of 390 non-schizophrenic as well as schizophrenic psychotics, and
      displayed common neurobiological abnormalities. Collaborative longitudinal
      studies using these economical methods might improve differential understanding
      and treatment of patients based upon these features rather than clinical
      symptoms.

PMID- 17559599
TI  - Thirty-five months experience of risperidone long-acting injection in a UK
      psychiatric service including a mirror-image analysis of in-patient care.
AB  - OBJECTIVE: To report the use of risperidone long-acting injection (RLAI) in a UK
      psychiatric service. METHOD: Retrospective case note review of all patients
      prescribed RLAI over a 35-month period. In the mirror-image analysis patients
      initiated on RLAI as in-patients had the index admission attributed to previous
      treatment. RESULTS: Patients prescribed RLAI had significantly higher baseline
      rates of drug misuse, alcohol misuse, unemployment and forensic markers than
      control patients prescribed oral antipsychotics. Most patients started RLAI
      because of poor compliance with oral antipsychotics. Inefficacy accounted for
      more discontinuations than intolerability. Fifty-eight percent (39/67) of
      patients were continuing RLAI 12 months after initiation. Mirror-image analysis
      (n = 74) showed that RLAI was associated with a reduction in the number of
      admissions (65 vs. 33, P < 0.005) and in total in-patient days (4550 vs. 2188
      days, P < 0.005). The mean reduction in in-patient care was 29 days per patient
      year of treatment, equivalent to a net financial saving over the acquisition and
      administration costs of RLAI of pound1172. CONCLUSION: Risperidone long-acting
      injection was associated with reduced in-patient care and was cost-effective.

PMID- 17559600
TI  - Why people do not take their psychotropic drugs as prescribed: results of the
      2000 National Psychiatric Morbidity Survey.
AB  - OBJECTIVE: We examined the prevalence and determinants of the reasons given for
      non-adherence to psychiatric medication in a representative community survey.
      METHOD: We used data for all participants taking oral psychotropic medication (n
      = 634) from the 2000 British Survey of National Psychiatric Morbidity. RESULTS:
      Of participants interviewed, 217 (34.2%) reported incomplete adherence to their
      psychiatric medication. Reasons given included forgetting, losing, running out
      (37.4%); thinking medication unnecessary (24.6%); reluctance to take drugs
      (18.9%) and side-effects (14.2%). Those giving forgetfulness or side-effects as
      reasons were younger. Side-effects were reported more frequently by people with a
      lower IQ or with psychosis. Those taking Selective Serotonin Reuptake Inhibitors
      were more likely to forget to take their medication. CONCLUSION: Two-fifths of
      people reported that missing their medication was a decision taken because they
      did not want it or think it necessary. Side-effects are a relatively uncommon
      reason for under-medication. Our results have implications for interventions to
      assist adherence.

PMID- 17559601
TI  - Clinical epidemiologic first-episode psychosis: 1-year outcome and predictors.
AB  - OBJECTIVE: To describe 1-year outcome in a large clinical epidemiologic sample of
      first-episode psychosis and its predictors. METHOD: A total of 301 patients with
      first-episode psychosis from four healthcare sectors in Norway and Denmark
      receiving common assessments and standardized treatment were evaluated at
      baseline, at 3 months, and at 1 year. RESULTS: Substantial clinical and social
      improvements occurred within the first 3 months. At 1-year 66% were in remission,
      11% in relapse, and 23% continuously psychotic. Female gender and better
      premorbid functioning were predictive of less severe negative symptoms. Shorter
      DUP was predictive for shorter time to remission, stable remission, less severe
      positive symptoms, and better social functioning. Female gender, better premorbid
      social functioning and more education also contributed to a better social
      functioning. CONCLUSION: This first-episode sample, being well treated, may be
      typical of the early course of schizophrenia in contemporary centers.

PMID- 17559602
TI  - Prevalence and correlates of comorbidity 8 years after a first psychotic episode.
AB  - OBJECTIVE: While rates and correlates of comorbidity have been investigated in
      the early course of psychosis, little is known about comorbidity in the medium-to
      longer term or its relationship with outcome. METHOD: A total of 182 first
      episode psychosis (FEP) patients who met DSM-IV criteria for a current psychotic
      disorder 8 years after index presentation were grouped according to concurrent
      comorbidity [no concurrent axis I disorder; concurrent substance use disorder
      (SUD); other concurrent axis I disorder; concurrent SUD and other axis I
      disorder]. Outcomes were compared between groups controlling for relevant
      covariates. RESULTS: As much as 39% met criteria for one or more concurrent axis
      1 diagnoses. Comorbidity was associated with greater severity of general
      psychopathology, but not with measures of functioning, treatment or negative
      symptoms. CONCLUSION: Specific combinations of comorbid disorders may influence
      patterns of psychotic symptomatology. Routine examination of axis I disorders is
      warranted in the ongoing management of psychosis.

PMID- 17559603
TI  - The dynamics of symptomatic and non-symptomatic coping with psychotic symptoms in
      the flow of daily life.
AB  - OBJECTIVE: Previous research has suggested that going along with psychotic
      symptoms (symptomatic coping) is less effective than other coping strategies with
      psychotic symptoms. This pilot study aims to validate such findings using a
      momentary assessment strategy of coping with stress in daily life. METHOD:
      Patients with psychosis (n = 35) were studied with the Experience Sampling Method
      (ESM; a structured diary technique) to assess coping with stress in daily life.
      This was analysed in relation to coping with psychotic symptoms using a
      previously validated interview (Maastricht Assessment of Coping Strategies).
      RESULTS: Symptomatic and non-symptomatic coping were negatively associated with
      each other. Symptomatic coping was negatively associated with the level of coping
      in daily life, whereas a positive association was apparent for non-symptomatic
      coping. Non-symptomatic coping, but not symptomatic coping, predicted appraisals
      of distress associated with psychotic symptoms. CONCLUSION: Effective coping may
      be associated with the tendency to develop conscious appraisals of distress
      associated with psychotic symptoms.

PMID- 17559605
TI  - Excessive yawning is common in the bulbar-onset form of ALS.

PMID- 17559606
TI  - Diagnostic confusion - EOS or frontal dementia.

PMID- 17559610
TI  - Effects of a self-management arthritis programme with an added exercise component
      for osteoarthritic knee: randomized controlled trial.
AB  - AIM: This paper is a report of a study to assess the effect of an adapted
      arthritis self-management programme with an added focus on exercise practice
      among osteoarthritic knee sufferers. BACKGROUND: Osteoarthritis of the knee is a
      major source of loss of function in older people. Previous studies have found
      self-management programmes to be effective in increasing arthritis self-efficacy
      and in mastery of self-management practice. METHOD: A randomized control trial
      was carried out from December 2002 to May 2003 and 120 participants (65.9%,
      including 67 in intervention group and 53 in control group) completed the 16-week
      postintervention assessments. Outcome measures included arthritis self-efficacy,
      use of self-management techniques, pain intensity and daily activity. FINDINGS:
      At 16 weeks, there was a 'statistically' significant improvement in the arthritis
      self-efficacy level (P <or= 0.001), in most of the self-management skills, i.e.
      use of cold and hot compresses, in two of three joint protective practices (P
      <or= 0.001; P = 0.01), an increase in the duration of light exercise practice (P
      <or= 0.001), reduction of current arthritis pain (P <or= 0.001) and in the
      ability to perform daily activities (P <or= 0.001) among the intervention group
      but not for the control group (P-range from 0.04 to 0.95). One joint protective
      practice showed a statistically significant increase in both groups (P <or=
      0.001). CONCLUSION: Our findings add to evidence showing short-term beneficial
      effects of self-efficacy theory in education programmes. Self-efficacy theory has
      great potential for empowering sufferers of chronic conditions to live with their
      illness.

PMID- 17559611
TI  - Capacity building in nursing and midwifery research and development: an old
      priority with a new perspective.
AB  - AIM: This paper is a report of a study to identify strategic priorities to inform
      the development of a regional strategy for nursing and midwifery research and
      development. BACKGROUND: Research capacity has been highlighted internationally
      as a crucial element in the advancement of nursing and midwifery research and
      development. Research capacity has been defined as that which relates to the
      ability to conduct research. In a strategic context, however, there is a broader
      perspective that encompasses activities related both to 'using' and 'doing'
      research. METHODS: A modified nominal group technique was employed. Three rounds
      were used to identify the main strategic priorities for nursing and midwifery
      research and development. Round one was based on the Delphi Technique and further
      rounds were based on the nominal group technique approach. Data were collected
      during February 2005. Participants (n = 105) were those involved in the research
      and development agenda for nursing and midwifery in Northern Ireland. FINDINGS:
      Capacity building was highlighted as a central component from the final 12
      priorities, with three key areas identified: (1) the importance of strong and
      visible leadership; (2) developing research expertise that will enable the
      profession to deliver programmes of research and (3) increasing the capacity of
      individuals and organizations to engage in development activity. CONCLUSION: The
      12 priorities identified emphasize the need for a broad perspective on building
      capacity that reflects involvement in a range of activities that span 'research'
      and 'development'. This has important implications globally if nurses and
      midwives are to develop the knowledge and skills required to engage in research
      and development as an integral part of their practice. Embracing this broader
      perspective has the potential to enhance performance that will contribute to
      continuous quality improvement.

PMID- 17559612
TI  - Nursing qua nursing: the connection between nursing knowledge and nursing
      shortages.

PMID- 17559614
TI  - The gap between dental education and clinical treatment in temporomandibular
      disorders and orofacial pain.
AB  - Implementation of research findings in patient care ideally will follow in a
      continuous cycle, and clinical questions from practitioners should stimulate
      research. Even in the most optimal situations, there will be a gap between the
      steady flow of new findings from research and their eventual implementation in
      clinical practice. In the clinical practice of temporomandibular disorders and
      orofacial pain (TMD/OFP) simple cases outnumber the more complex cases by far.
      Therefore, research implications for the general dental practitioner, whose
      patients are rarely represented in research populations, may differ from what is
      published and taught. Treatment options like counselling, occlusal treatments
      (reversible as a rule and irreversible by exception) and physiotherapy can be
      very successful in the hands of the general dental practitioner. European dental
      schools should define additional amendments to the recently proposed profile and
      competencies for the European dentist, in order to focus on the relevant and
      current knowledge on temporomandibular disorders and orofacial pain. These
      amendments should address the adequate diagnosis and management of non-complex
      TMD cases and the need to refer to a TMD/OFP specialist in complex cases.
      Professional organizations such as the European Academy of Craniomandibular
      disorders can endorse better TMD/OFP education and training.

PMID- 17559615
TI  - Electromyographic activity of masticatory, neck and trunk muscles of subjects
      with different skeletal facial morphology--a cross-sectional evaluation.
AB  - The electromyographic pattern activity of masticatory, neck and trunk muscles was
      assessed using surface electromyography (sEMG) in 60 Caucasian adult females (20
      subjects in skeletal class I, 20 subjects in skeletal class II and 20 subjects in
      skeletal class III), classified on the base of their skeletal class (ANB angle),
      corrected on the base of maxillary and mandibular rotations. The sEMG activity
      was recorded at mandibular rest position and during maximal voluntary clenching.
      At mandibular rest position, the sEMG activities of masseter and anterior
      temporal muscles were significantly higher in class III subjects than in class I
      and class II subjects, that showed no significant difference between them. Then,
      the sEMG activities of posterior cervicals and upper trapezius were significantly
      higher in skeletal class III subjects than in the other two groups. During
      maximal voluntary clenching, no significant difference was observed in the sEMG
      activity of masticatory muscles among the three considered groups. However, the
      sEMG activities of posterior cervicals and upper trapezius were significantly
      higher in skeletal class III subjects than in the other two groups, which showed
      no significant difference between them. In conclusion, the skeletal class seems
      to affect the sEMG pattern activity of masticatory, neck and trunk muscles.

PMID- 17559616
TI  - Analysis of brain activity immediately before conscious teeth clenching using
      magnetoencephalographic method.
AB  - The reasons for unconscious teeth clenching have not been clarified. The long
      term goal of our project was the elucidation of processing in the brain
      immediately before unconscious teeth clenching, in order to clarify its
      significance in humans. The objective of the present study was to establish a
      magnetoencephalographic (MEG) method of measuring brain activity immediately
      before clenching, and to clarify the time-course of brain activity immediately
      before conscious clenching. We measured the MEG signal in six subjects before,
      during and after clenching in a protocol that restricted head movement <5 mm. We
      derived tomographic estimates of brain activity for each time slice of data, as
      well as time courses for regional brain activations. Analysis of the tomographic
      images and time courses yielded statistical maps of activity in the motor, pre
      motor and somatosensory cortices immediately before clenching in all subjects.
      Activations were found bilaterally, but with a strong unilateral bias in most
      subjects. Our results demonstrate that the MEG procedures, we have introduced are
      capable of measuring brain activity immediately before clenching, and indicate
      that analysis should begin from at least 200 ms before electromyogram onset.

PMID- 17559617
TI  - Factors associated with taste dissatisfaction in the elderly.
AB  - The purpose of this study was to investigate taste sensation in the elderly, and
      to determine relationships between subjective dissatisfaction with taste ability
      and factors such as age, gender and oral status among independently living
      elderly individuals. Participants were older adults (mean age, 66.0 +/- 4.2
      years; 321 men and 319 women) voluntarily attending a Senior Citizen Educational
      Program supported by local government in 2003 and 2004. The questionnaire
      included self-assessed items on general health, dry mouth, chewing satisfaction
      and taste satisfaction. Respondents underwent investigation of salivary flow
      rate, dental status and gustatory testing using the filter-paper disc method for
      sweet, salty, sour and bitter. Chi-squared tests showed that the factors
      associated with dissatisfaction with taste ability were older age,
      dissatisfaction with chewing, dry mouth during eating and wearing dentures
      covering the entire hard palate. The sensation for each taste was not
      significantly related to taste satisfaction by chi-squared test. Multiple
      logistic regression analysis showed that dry mouth during eating, dentures
      covering the entire hard palate, dissatisfaction with chewing and discriminatory
      threshold for the sour taste were associated with dissatisfaction with taste
      ability. We found a significant association between subjective taste
      dissatisfaction and certain oral factors; hence, when patients complain about
      diminished taste, dentists must assess oral status as well as taste sensation.

PMID- 17559618
TI  - The effect of core framework designs on the fracture loads of all-ceramic fixed
      partial dentures on posterior implants.
AB  - This study evaluated the fracture loads of three-unit all-ceramic bridges on
      implants; the core frameworks of the bridges were made of zirconium oxide. Three
      core framework designs were fabricated according to the design of the bars
      between the retainers: (i) straight, (ii) curved in the occlusal direction, or
      (iii) curved in the gingival direction. A static load was applied at the centre
      of the pontic, and the mean initial crack and final fracture loads were measured
      and compared. The core framework curved in the occlusal direction had the highest
      final fracture loads; there were significant differences (P < 0.05) in the mean
      final fracture load, whereas initial fracture load, which fractured of veneered
      porcelain, did not show significant differences among three designs. The all
      ceramic bridges on the implants made with Procera zirconium core frameworks had
      high final fracture load. The core framework design that curved in the occlusal
      direction helped the framework withstand the occlusal load, which results in
      reliable prostheses, especially in the molar region.

PMID- 17559619
TI  - Cross-sectional analysis of the implant-abutment interface.
AB  - The purpose of this study was to develop a technique to evaluate the implant
      abutment gap of an external hexagon implant system as a function of radius. Six
      implants of 3.75 mm in diameter (Conexao Sistema de Protese Ltda, Sao Paulo,
      Brazil) and their respective abutments were screw connected and torqued to 20 N
      cm(-1). The implants were mounted in epoxy assuring an implant long-axis position
      perpendicular to the vertical axis. Each implant was grounded through its
      thickness parallel to implant long-axis at six different distance interval.
      Implant-abutment gap distances were recorded along the implant-abutment region
      for each section. Individual measurements were related to their radial position
      through trigonometric inferences. A sixth degree polynomial line fit approach
      determined radial adaptation patterns for each implant. Micrographs along implant
      sections showed a approximately 300 mum length implant-abutment engagement
      region. All implants presented communication between external and internal
      regions through connection gaps and inaccurate implant-abutment alignment.
      Average gap distances were not significantly different between implants (P >
      0.086). Polynomial lines showed implant-abutment gap values below 10 mum from 0
      mum to approximately 250 mum of the implant-abutment engagement region. Gap
      distances significantly increased from approximately 250 mum to the outer radius
      of the implant-abutment engagement region. The technique described provided a
      broader scenario of the implant-abutment gap adaptation compared with previous
      work concerning implant-abutment gap determination, and should be considered for
      better understanding mechanical aspects or biological effects of implant-abutment
      adaptation on peri-implant tissues.

PMID- 17559620
TI  - Osseointegration of anodized titanium implants under different current voltages:
      a rabbit study.
AB  - The oxide layer that covers a titanium surface is extremely stable and appears to
      have excellent biocompatibility, which can result in successful osseointegration.
      The aim of this study was to analyse the characteristics of an oxide layer formed
      by anodic oxidation (anodization), and to evaluate the extent of bone healing
      around the anodized implant. The screw-type implants were made of commercially
      pure titanium (Grade 2). The Group 1 samples had a turned surface, and three
      other types of experimental specimens were anodized under constant voltages of
      190 V (Group 2), 230 V (Group 3) and 270 V (Group 4). The surface characteristics
      of each sample type were inspected. Removal torque was measured after a 4-week
      healing period and the histomorphometric analysis was performed 6 weeks after
      implantation in rabbit tibiae. There was an increase in both the size and number
      of pores as the anodizing voltage increased. The Ra value of the Group 4 samples
      was higher than those in the Group 1 and 2 samples (P < 0.05). Group 3 showed a
      difference compared with Group 1 (P < 0.05). A thicker oxide layer, which
      contained crystalline (anatase) TiO(2) with the inclusion of some electrolytes
      (Ca, P), was formed at the higher anodizing voltage. Group 4 had higher removal
      torque values and percentages of bone-to-implant contact than the other groups (P
      < 0.05). The anodized titanium implants showed more intimate and stronger
      connections with peri-implant bone during early osseointegration than the turned
      titanium implants in this experimental model.

PMID- 17559621
TI  - Structure, castability and mechanical properties of commercially pure and alloyed
      titanium cast in graphite mould.
AB  - This report is a study of structure, castability, mechanical properties as well
      as corrosion behaviour of titanium doped with up to 5 weight percentage (wt%) of
      a series of alloy elements, including Ta, Mo, Nb, Hf, Zr, Sn, Bi and Ag. The
      results indicate that, with addition of 1 wt% alloy element, Bi and Mo were most
      effective in enhancing the castability of titanium. With more alloy elements
      added, the castability values of most alloys more or less decreased. Except Ti-Mo
      system, all Ti alloys with a fine acicular morphology had the same crystal
      structure (hcp) as that of c.p. Ti with a typical lath type morphology. When 3
      wt% or more Mo was added, a finer orthorhombic alpha'' phase was formed. The
      microhardness and bending strength values of Ti alloys were all higher than those
      of c.p. Ti. Among all alloys, Ti-Mo system exhibited the highest hardness and
      strength level. For a certain alloy, the bending strength did not necessarily
      increase with its alloy content. Except Ti-5Zr and Ti-Mo alloys, the bending
      moduli of most alloy systems were not much different from that of c.p. Ti. All
      alloys showed an excellent resistance to corrosion in Hanks' solution at 37
      degrees C.

PMID- 17559622
TI  - Variation in structure and properties of a non-dispersive TTCP/DCPA-derived CPC
      immersed in Hanks' solution.
AB  - The present work is to characterize a non-dispersive, fast-setting and high
      strength tetra calcium phosphate (TTCP)/dicalcium phosphate anhydrous (DCPA)
      based calcium phosphate cement (nd-CPC) recently developed in the authors'
      laboratory. Comparison between this CPC and a conventional TTCP/DCPA-based CPC (c
      CPC) is made. The results show that, during setting c-CPC reaches its pH plateau
      after 10 min, while nd-CPC approaches plateau after 20 min. During immersion in
      Hanks' solution the pH values of both cements reach their maxima after immersion
      for a few days, then decline eventually to near neutrality. With immersion time
      TTCP and DCPA phases gradually dissolve and apatite phase precipitates. The nd
      CPC has a higher apatite formation rate and denser structure than c-CPC under
      similar conditions, especially at early stage. The nd-CPC also demonstrates
      higher strength both during setting and after immersion.

PMID- 17559623
TI  - Differential expression of receptor activator of nuclear factor-kappaB ligand and
      osteoprotegerin mRNA in periodontal diseases.
AB  - BACKGROUND AND OBJECTIVE: Receptor activator of nuclear factor-kappaB ligand
      (RANKL) is responsible for the induction of osteoclastogenesis and bone
      resorption, whereas its decoy receptor, osteoprotegerin, can directly block this
      action. Because this dyad of cytokines is crucial for regulating the bone
      remodelling process, imbalances in their expression may cause a switch from the
      physiological state to enhanced bone resorption or formation. This study
      investigated the mRNA expression of RANKL and osteoprotegerin, as well as their
      relative ratio, in the gingival tissues of patients with various forms of
      periodontal diseases. MATERIAL AND METHODS: Gingival tissue was obtained from
      nine healthy subjects and 41 patients, who had gingivitis, chronic periodontitis,
      generalized aggressive periodontitis, and chronic periodontitis and were
      receiving immunosuppressant therapy. Quantitative real-time polymerase chain
      reaction was employed to evaluate the mRNA expression of RANKL and
      osteoprotegerin in these tissues. RESULTS: Compared with healthy individuals,
      patients in all periodontitis groups, but not those with gingivitis, exhibited
      stronger RANKL expression and a higher relative RANKL/osteoprotegerin ratio. In
      addition, osteoprotegerin expression was weaker in patients with chronic
      periodontitis. When patients with generalized aggressive periodontitis and
      chronic periodontitis were compared, the former exhibited stronger RANKL
      expression, whereas the latter exhibited weaker osteoprotegerin expression, and
      there was no difference in their relative ratio. When chronic periodontitis
      patients were compared with chronic periodontitis patients receiving
      immunosuppressant therapy, osteoprotegerin, but not RANKL, expression was
      stronger in the latter. CONCLUSION: This study demonstrates that RANKL and
      osteoprotegerin expression are differentially regulated in various forms of
      periodontitis, and the relative RANKL/osteoprotegerin ratio appears to be
      indicative of disease occurrence. This information may confer diagnostic and
      therapeutic value in periodontitis.

PMID- 17559624
TI  - In vivo experimental model of human gingival mucosa using immunodeficient mice.
AB  - BACKGROUND AND OBJECTIVE: To establish an in vivo experimental model for
      examining human periodontal tissue, the present study examined several transplant
      techniques that maintain the structure and characteristics of human gingival
      mucosa. MATERIAL AND METHODS: Human oral mucosal tissue samples were collected
      from the gingiva (n = 11), palate (n = 1), and tongue (n = 3). These mucosal
      grafts were transplanted onto BALB/c nu/scid mice with double-mutant
      immunodeficiency. Murine skin, twice the size of the graft, was cut open in an '
      square superset'-shape. Next, the connective tissue side of the graft was placed
      onto the murine connective tissue. Immunohistochemical analysis was also
      performed, using polyclonal rabbit antibody to involucrin, monoclonal antibody to
      vimentin, monoclonal antibody to CD34, and monoclonal antibody to Ki-67, to
      determine whether the characteristics of human oral mucosa were maintained.
      RESULTS: When the connective tissue side of the graft was placed on the murine
      fascial membrane, the histological structure of the graft was maintained for 60
      d. These grafts were examined for human characteristics using human-specific
      antibodies. Immunohistochemically, the expression patterns of involucrin,
      vimentin, and Ki-67 indicated that transplanted mucosa revealed normal human
      characteristics, including differentiation and proliferation up to 80 d. CD34 was
      not detected in the graft endothelial cells. CONCLUSION: The present study
      revealed that the novel technique of transplantation of human gingival mucosa in
      nu/scid mice may serve as an in vivo experimental model of periodontal disease.

PMID- 17559625
TI  - Leptin levels in gingival crevicular fluid in periodontal health and disease.
AB  - BACKGROUND AND OBJECTIVE: A high concentration of leptin is associated with
      healthy gingival tissue, and the concentration of leptin decreases as periodontal
      disease progresses. However, to date, the leptin concentration in gingival
      crevicular fluid has not been documented. Hence, the present study was carried
      out to explore the presence of leptin in gingival crevicular fluid in periodontal
      health and disease, and to probe further into its possible role in periodontal
      disease progression. MATERIAL AND METHODS: A total of 45 adult patients were
      selected, based on their body mass index, for the study. They were categorized
      into three groups of 15 patients each, based on their periodontal tissue status,
      as follows: group I (clinically healthy gingiva with no loss of attachment);
      group II (chronic gingivitis with no loss of attachment); and group III (chronic
      periodontitis). Gingival crevicular fluid samples of 1 microL were collected
      extracrevicularly using white color-coded 1-5 microL calibrated volumetric
      microcapillary pipettes from one site in each person, and samples were analyzed
      for leptin using a commercially available enzyme-linked immunosorbent assay kit.
      RESULTS: The concentration of leptin in gingival crevicular fluid of patients in
      group I (2292.69 pg/mL) was statistically higher (p < 0.05) than in those of
      groups II (1409.95 pg/mL) and III (1071.89 pg/mL). This suggests a negative
      correlation of gingival crevicular fluid leptin concentration with clinical
      attachment loss (p < 0.05). CONCLUSION: As periodontal tissue destruction
      increased, there was a substantial decrease in gingival crevicular fluid leptin
      concentration. This observation extends our knowledge of the protective role of
      leptin in periodontal health.

PMID- 17559626
TI  - Association of gene polymorphisms for plasminogen activators with alveolar bone
      loss.
AB  - BACKGROUND AND OBJECTIVE: The plasminogen activating system is a
      protease/inhibitor system central to extracellular matrix remodeling with a
      suggested role in periodontal disease pathology. A few studies have reported
      polymorphisms in the genes of plasminogen activator inhibitors to be associated
      with periodontal disease severity. Two gene polymorphisms - a BamHI restriction
      fragment length polymorphism in the urokinase plasminogen activator gene (uPA)
      and a HindIII restriction fragment length polymorphism in the plasminogen
      activator inhibitor type 1 gene (PAI-1) - have been associated with conditions
      having a vascular component, and our objective was to assess the association of
      these gene polymorphisms with alveolar bone loss in chronic periodontal disease
      of adults. MATERIAL AND METHODS: Genotype was determined by polymerase chain
      reaction amplification of whole blood, pertinent histories were obtained by
      interview, and alveolar bone loss was assessed from current radiographs. RESULTS:
      In 77 elderly patients with a normal distribution of alveolar bone loss, we
      demonstrated a significant association between levels of alveolar bone loss and
      these polymorphisms in the uPA and PAI-1 genes. Controlling for the contributions
      of smoking or diabetes to periodontal bone loss, estimated odds ratios for
      predicting lower levels of alveolar bone loss, associated with a greater degree
      of periodontal health, were strongest when defined by the concurrent presence of
      a homozygous urokinase plasminogen activator genotype and the nuclease-sensitive
      plasminogen activator inhibitor type 1 (HindIII) allele (odds ratio = 2.6; 95%
      confidence interval: 5.8-1.3). CONCLUSION: The urokinase plasminogen activator
      (BamHI) and plasminogen activator inhibitor type 1 (HindIII) genotypes may serve
      as useful markers for heritability of bone loss associated with periodontal
      disease.

PMID- 17559627
TI  - Interclinician disparity in periodontal decision making: need for consensus
      statements on surgical treatment.
AB  - BACKGROUND AND OBJECTIVE: The clinical factors involved in the decision-making
      process for surgical treatment have been described. However, there is still
      little standardization of the criteria upon which such a decision should be
      based. The impact of this lack of practice guidelines on the recommendation of
      surgery in clinical practice is unclear. The objective of the present study was
      to investigate the recommendation of surgical therapy during the
      corrective/reparative treatment phase by trained clinicians with various
      backgrounds on the basis of clinical data. MATERIAL AND METHODS: Fifteen
      clinicians (10 periodontal students and/or recent graduates from two dental
      schools and five experienced practitioners) were asked to make a treatment
      decision (surgery or no surgery) at a tooth level. Therefore, they were given 23
      initially treated patients with details on demographics and smoking habits.
      Radiographs and clinical information on 573 teeth at baseline (prior to root
      debridement) and at 9 mo of follow-up were provided. RESULTS: Clinicians
      interpret clinical data quite differently in their advice of surgery when
      practice guidelines are not provided, as the results showed high variation in
      surgical recommendation. Experienced practitioners showed most variation, with a
      range from 13 to 50% in surgical recommendation. Clinicians linked to a training
      center shared a common treatment philosophy as to when periodontal surgery should
      be performed. This philosophy differed markedly among the two dental schools.
      Most disagreement among the 15 clinicians was found for deep pockets and for
      multirooted teeth. Disease status, tooth type, age, and full-mouth plaque levels
      had a significant impact on decision making. CONCLUSION: The substantial
      variation in recommending surgery calls for consensus statements on surgical
      treatment.

PMID- 17559628
TI  - Comparison of experimental gingivitis with persistent gingivitis: differences in
      clinical parameters and cytokine concentrations.
AB  - BACKGROUND AND OBJECTIVE: Experimental gingivitis has been studied extensively as
      a well-controlled laboratory model of gingivitis. It is unclear, however, how
      experimental gingivitis compares with persistent plaque and gingivitis in more
      naturalistic settings. The present study compares both conditions in a randomized
      controlled design. MATERIAL AND METHODS: Twenty-six students suffering from
      plaque and gingivitis were randomly assigned to either a persistent gingivitis or
      an experimental gingivitis condition. Subjects with persistent gingivitis
      continued their habitual (i.e. insufficient) oral hygiene behaviour, resulting in
      persistence of plaque and gingivitis. Experimental gingivitis consisted of
      initial prophylaxis and subsequent total neglect of oral hygiene. Crevicular
      interleukin-1beta and interleukin-8 and clinical data were assessed weekly.
      RESULTS: After 4 wk, subjects with experimental gingivitis showed significantly
      more plaque accumulation (p = 0.005), higher interleukin-1beta (p = 0.037), and
      lower interleukin-8 (p = 0.043) concentrations than subjects with persistent
      gingivitis. Whereas in experimental gingivitis we observed considerable
      fluctuations in clinical and immunological parameters over the 4-wk period,
      persistent gingivitis was characterized by little fluctuation, indicating that we
      were monitoring an inflammatory steady state. CONCLUSION: The data indicate that
      conditions observed after 4 wk of experimental gingivitis are not comparable with
      persistent gingival inflammation in a naturalistic setting. Results are discussed
      with respect to current studies, indicating that chronic inflammation may reflect
      a stage of down-regulated pro-inflammatory response.

PMID- 17559629
TI  - Neutrophil elastase is involved in the initial destruction of human periodontal
      ligament.
AB  - BACKGROUND AND OBJECTIVE: It has been reported that noncollagenous proteins may
      provide mechanical strength to the periodontal ligament. Several proteolytic
      activities, including that of neutrophil elastase, are reported to increase
      significantly in periodontal disease. The aim of this study was to investigate
      the function of neutrophil elastase in the initial destruction of periodontal
      ligament at early stages of periodontal disease. MATERIAL AND METHODS: The
      detection and identification of proteinases in chronic periodontitis and healthy
      periodontal ligament were examined by zymographic and zymo-Western analysis. The
      morphological changes of periodontal ligament, digested with or without authentic
      proteinases, were observed using scanning electron microscopy. RESULTS: Increases
      in neutrophil elastase, plasminogen, and matrix metalloproteinase-9 were detected
      in periodontal ligament from chronic periodontitis, compared with healthy
      periodontal ligament. Among these proteinases, only neutrophil elastase digested
      the intact noncollagenous proteins of periodontium. When human healthy
      periodontal ligament was directly digested by neutrophil elastase in an in vitro
      system, the morphological features were quite similar to that of the periodontal
      ligament in chronic periodontitis . In healthy periodontal ligament, the collagen
      fibrils are covered with noncollagenous proteins containing 110 kDa acidic
      glycoprotein, which was degraded initially by the neutrophil elastase.
      CONCLUSION: It was concluded that neutrophil elastase is involved in the
      degradation of noncollagenous protein-covered collagen fibrils in the early
      destructive stages of periodontal disease.

PMID- 17559630
TI  - Defense mechanism of heme oxygenase-1 against cytotoxic and receptor activator of
      nuclear factor-kappaB ligand inducing effects of hydrogen peroxide in human
      periodontal ligament cells.
AB  - BACKGROUND AND OBJECTIVE: Although induction of heme oxygenase-1 by H2O2 has been
      reported, the protective role of heme oxygenase-1 against the cytotoxic and
      osteoclastogenic effects of H2O2 have not been elucidated in human periodontal
      ligament cells. The aim of this work was to investigate the defense mechanism of
      heme oxygenase-1 on H2O2-induced cytotoxicity and to analyze the expression of
      receptor activator of nuclear factor-kappaB ligand (RANKL) and osteoprotegerin as
      markers for osteoclast differentiation in periodontal ligament cells. MATERIAL
      AND METHODS: Using human periodontal ligament cells, cytotoxicity was measured by
      the 3,4,5-dimethylthiazol-2-yl-2,5-diphenyl tetrazolium bromide (MTT) assay, and
      expression of heme oxygenase-1, RANKL, and osteoprotegerin mRNA was determined by
      reverse transcription-polymerase chain reaction. RESULTS: H2O2 produced a
      cytotoxic effect by reducing the cell viability and enhancing the expression of
      heme oxygenase-1 and RANKL mRNAs in a concentration- and time-dependent manner.
      Additional experiments revealed that heme oxygenase-1 inducer (hemin), a membrane
      permeable cGMP analog (8-bromo-cGMP), carbon monoxide, extracellular signal
      regulated kinase, p38 mitogen-activated protein kinase inhibitor, protein kinase
      inhibitor (KT5823), and nuclear factor-kappaB inhibitor (pyrrolidine
      dithiocarbamate) also blocked the effects of H2O2 on cell viability and RANKL
      mRNA expression in periodontal ligament cells. CONCLUSION: These data suggest
      that heme oxygenase-1 induction plays a protective role in periodontal ligament
      cells against the cytotoxic and RANKL-inducing effects of H2O2, through multiple
      signaling pathways.

PMID- 17559631
TI  - Lack of association between chronic periodontitis and the Toll-like receptor 4
      gene polymorphisms in a Czech population.
AB  - BACKGROUND AND OBJECTIVE: Periodontitis is a bacterially induced chronic
      inflammatory disease and a major cause of tooth loss among adults. Toll-like
      receptors are signal molecules essential for the cellular response to bacterial
      cell wall components. The aim of this study was to investigate relationships
      between chronic periodontitis and variations in the TLR4 gene. MATERIAL AND
      METHODS: A total of 171 patients with chronic periodontitis and 218 unrelated
      controls were genotyped for the Asp299Gly (896A>G) and Thr399Ile (1196C>T)
      polymorphisms of the TLR4 gene. RESULTS: Both variants were in nearly complete
      linkage disequilibrium. No homozygotes for the less common alleles, 299Gly and
      399Thr, respectively, were found. The prevalence of the Asp299Gly and the
      Thr399Ile heterozygotes was 5.3% and 5.0% in controls, and 7.0% and 7.0% in
      periodontitis patients. CONCLUSION: In conclusion, TLR4 gene polymorphisms were
      not significantly associated with the susceptibility to, or severity of, chronic
      periodontitis in our population.

PMID- 17559632
TI  - Diabetes-related parameters and periodontal conditions in children.
AB  - BACKGROUND AND OBJECTIVE: The relationship between diabetes and periodontal
      diseases is well established. Our aim in this study was to explore the diabetes
      related parameters that are associated with accelerated periodontal destruction
      in diabetic youth. MATERIAL AND METHODS: Three-hundred and fifty 6-18-year-old
      children with diabetes received a periodontal examination. Data on important
      diabetes-related variables were collected. Analyses were performed using logistic
      regression, with gingival/periodontal disease as the dependent variable, for the
      whole cohort and separately for two subgroups (6-11 and 12-18 years of age).
      RESULTS: Regression analyses, adjusting for age, gender, ethnicity, frequency of
      prior dental visits, dental plaque, and dental examiner, revealed a strong
      positive association between mean hemoglobin A1c over the 2 years prior to
      inclusion in the study and periodontitis (odds ratio = 1.31, p = 0.030). This
      association approached significance in the younger subgroup (odds ratio = 1.56, p
      = 0.052, n = 183). There was no significant relationship between diabetes
      duration or body mass index-for-age and measures of gingival/periodontal disease
      in this cohort. CONCLUSION: These findings suggest that accelerated periodontal
      destruction in young people with diabetes is related to the level of metabolic
      control. Good metabolic control may be important in addressing periodontal
      complications in young patients with diabetes, similarly to what is well
      established for other systemic complications of this disease.

PMID- 17559633
TI  - Lipid A-associated proteins from Porphyromonas gingivalis stimulate release of
      nitric oxide by inducing expression of inducible nitric oxide synthase.
AB  - BACKGROUND AND OBJECTIVE: The purpose of this study was to examine the effects of
      lipid A-associated proteins from Porphyromonas gingivalis, a major cause of
      inflammatory periodontal disease, on the production of nitric oxide and
      expression of inducible nitric oxide synthase in the murine macrophage cell line,
      RAW264.7. We also attempted to throw light on the signaling mechanisms involved
      in P. gingivalis lipid A-associated protein-induced nitric oxide production.
      MATERIAL AND METHODS: The lipid A-associated proteins from P. gingivalis 381 were
      prepared by standard hot phenol-water extraction of endotoxin isolated by the
      butanol method. Nitric oxide production was assayed by measuring the accumulation
      of nitrite in culture supernatants. Western blot analysis of inducible nitric
      oxide synthase and analysis of reverse transcription-polymerase chain reaction
      products were carried out. RESULTS: We found that P. gingivalis lipid A
      associated proteins can induce inducible nitric oxide synthase expression and
      stimulate the release of nitric oxide without additional stimuli, and we
      demonstrated that multiple signaling pathways, such as nuclear factor-kappaB,
      microtubule polymerization, protein tyrosine kinase, protein kinase C, and
      mitogen-activated protein kinase cascades, are involved in P. gingivalis lipid A
      associated protein-stimulated nitric oxide production. The production of nitric
      oxide required l-arginine. CONCLUSION: The present study clearly shows that P.
      gingivalis lipid A-associated proteins fully induced inducible nitric oxide
      synthase expression and nitric oxide production in RAW264.7 cells in the absence
      of other stimuli. The ability of P. gingivalis lipid A-associated proteins to
      promote the production of nitric oxide may be important in the pathogenesis of
      inflammatory periodontal disease.

PMID- 17559634
TI  - Periodontitis and premature death: a 16-year longitudinal study in a Swedish
      urban population.
AB  - BACKGROUND AND OBJECTIVE: Growing experimental evidence implicates chronic
      inflammation/infection due to periodontal diseases as a risk factor for death.
      The objective was to evaluate the role of periodontitis in premature death in a
      prospective study. METHODS: The causes of death in 3273 randomly-selected
      subjects, aged 30-40 years, from 1985 to 2001 were registered. At baseline, 1676
      individuals underwent a clinical oral examination (Group A) and 1597 did not
      (Group B). Mortality and causes of death from 1985 to 2001 were recorded
      according to ICD-9-10. RESULTS: In Groups A (clinically examined group) and B, a
      total of 110 subjects had died: 40 subjects in Group A, and 70 in Group B. In
      Group A significant differences were present at baseline between survivors and
      persons who later died, with respect to dental plaque, calculus, gingival
      inflammation and number of missing molars in subjects with periodontitis (p <
      0.001). The multiple logistic regression analysis results of the relationship
      between being dead (dependent variable) and several independent variables
      identified periodontitis with any missing molars as a principal independent
      predictor of death. CONCLUSIONS: Young individuals with periodontitis and missing
      molars seem to be at increased risk for premature death by life-threatening
      diseases, such as neoplasms, and diseases of the circulatory and digestive
      systems.

PMID- 17559635
TI  - Mitogen-activated protein kinases mediate interleukin-1beta-induced receptor
      activator of nuclear factor-kappaB ligand expression in human periodontal
      ligament cells.
AB  - BACKGROUND AND OBJECTIVE: Interleukin-1beta-stimulated receptor activator of
      nuclear factor-kappaB ligand (RANKL) expression in human periodontal ligament
      cells is partially mediated by endogenous prostaglandin E2, whereas mitogen
      activated protein kinases (MAPKs) are implicated in regulating various
      interleukin-1-responsive genes. We investigated herein the involvement of MAPKs
      in interleukin-1beta-stimulated RANKL expression in human periodontal ligament
      cells. MATERIAL AND METHODS: Human periodontal ligament cells were pretreated
      separately with specific inhibitors of MAPKs, including extracellular signal
      regulated kinase, p38 MAPK and c-Jun N-terminal kinase, and subsequently treated
      with interleukin-1beta. Following each treatment, the phosphorylation of each
      MAPK, the expression of RANKL, and the production of prostaglandin E2 were
      determined. RANKL activity was evaluated using an assay to determine the survival
      of prefusion osteoclasts. RESULTS: Interleukin-1beta induced RANKL expression at
      the mRNA and protein levels, as well as RANKL activity in human periodontal
      ligament cells. Interleukin-1beta also activated extracellular signal-regulated
      kinase, p38 MAPK, and c-Jun N-terminal kinase. Pretreatment with each MAPK
      inhibitor partially, but significantly, suppressed interleukin-1beta-induced
      RANKL expression and its activity, as well as prostaglandin E2 production.
      CONCLUSION: In human periodontal ligament cells, three types of MAPK inhibitor
      may abrogate RANKL expression and activity induced by interleukin-1beta, directly
      or indirectly through partial suppression of prostaglandin E2 synthesis. In
      addition, extracellular signal-regulated kinase, p38 MAPK, and c-Jun N-terminal
      kinase signals may co-operatively mediate interleukin-1beta-stimulated RANKL
      expression and its activity in those cells.

PMID- 17559636
TI  - Overexpression of interleukin-1beta and interleukin-6 may play an important role
      in periodontal breakdown in type 2 diabetic patients.
AB  - BACKGROUND AND OBJECTIVE: This study evaluated whether the biochemical changes
      associated with type 2 diabetes modulate the expression of interleukin-1beta,
      interleukin-6, interleukin-8, and interferon-gamma in sites with chronic
      periodontitis. MATERIAL AND METHODS: Biopsies were harvested and divided into
      three groups: group 1, systemically and periodontally healthy subjects (n = 10);
      group 2, systemically healthy subjects with moderate-to-severe chronic
      periodontitis (probing depth > 6 mm) (n = 20); and group 3, type 2 diabetic
      subjects with periodontitis (n = 20). Cytokine levels were assessed in the
      gingival tissues by enzyme-linked immunosorbent assay analysis. RESULTS: Data
      analysis demonstrated that the interleukin-1beta, interleukin-6, interleukin-8,
      and interferon-gamma levels were higher in the presence of periodontal
      inflammation than in the absence of inflammation, regardless of systemic status.
      The interleukin-1beta and interleukin-6 levels were higher in diabetic subjects
      (group 3) than in systemically healthy patients with comparable types of
      periodontitis (group 2). No difference was observed for the interleukin-8 and
      interferon-gamma levels between groups 2 and 3. CONCLUSION: Within the limits of
      this study, it was concluded that type 2 diabetes was associated with increased
      expression of interleukin-1beta and interleukin-6 in periodontally inflamed
      tissues of diabetic patients, relative to nondiabetic subjects, and that such
      overexpression may be involved in the mechanisms by which type 2 diabetes
      enhances periodontal destruction.

PMID- 17559637
TI  - Identifying regulatory targets of cell cycle transcription factors using gene
      expression and ChIP-chip data.
AB  - BACKGROUND: ChIP-chip data, which indicate binding of transcription factors (TFs)
      to DNA regions in vivo, are widely used to reconstruct transcriptional regulatory
      networks. However, the binding of a TF to a gene does not necessarily imply
      regulation. Thus, it is important to develop methods to identify regulatory
      targets of TFs from ChIP-chip data. RESULTS: We developed a method, called
      Temporal Relationship Identification Algorithm (TRIA), which uses gene expression
      data to identify a TF's regulatory targets among its binding targets inferred
      from ChIP-chip data. We applied TRIA to yeast cell cycle microarray data and
      identified many plausible regulatory targets of cell cycle TFs. We validated our
      predictions by checking the enrichments for functional annotation and known cell
      cycle genes. Moreover, we showed that TRIA performs better than two published
      methods (MA-Network and MFA). It is known that co-regulated genes may not be co
      expressed. TRIA has the ability to identify subsets of highly co-expressed genes
      among the regulatory targets of a TF. Different functional roles are found for
      different subsets, indicating the diverse functions a TF could have. Finally, for
      a control, we showed that TRIA also performs well for cell-cycle irrelevant TFs.
      CONCLUSION: Finding the regulatory targets of TFs is important for understanding
      how cells change their transcription program to adapt to environmental stimuli.
      Our algorithm TRIA is helpful for achieving this purpose.

PMID- 17559638
TI  - Effect of meteorological factors on clinical malaria risk among children: an
      assessment using village-based meteorological stations and community-based
      parasitological survey.
AB  - BACKGROUND: Temperature, rainfall and humidity have been widely associated with
      the dynamics of malaria vector population and, therefore, with spread of the
      disease. However, at the local scale, there is a lack of a systematic
      quantification of the effect of these factors on malaria transmission. Further,
      most attempts to quantify this effect are based on proxy meteorological data
      acquired from satellites or interpolated from a different scale. This has led to
      controversies about the contribution of climate change to malaria transmission
      risk among others. Our study addresses the original question of relating
      meteorological factors measured at the local scale with malaria infection, using
      data collected at the same time and scale. METHODS: 676 children (6-59 months)
      were selected randomly from three ecologically different sites (urban and rural).
      During weekly home visits between December 1, 2003, and November 30, 2004,
      fieldworkers tested children with fever for clinical malaria. They also collected
      data on possible confounders monthly. Digital meteorological stations measured
      ambient temperature, humidity, and rainfall in each site. Logistic regression was
      used to estimate the risk of clinical malaria given the previous month's
      meteorological conditions. RESULTS: The overall incidence of clinical malaria
      over the study period was 1.07 episodes per child. Meteorological factors were
      associated with clinical malaria with mean temperature having the largest effect.
      CONCLUSION: Temperature was the best predictor for clinical malaria among
      children under five. A systematic measurement of local temperature through ground
      stations and integration of such data in the routine health information system
      could support assessment of malaria transmission risk at the district level for
      well-targeted control efforts.

PMID- 17559639
TI  - MAK-4 and -5 supplemented diet inhibits liver carcinogenesis in mice.
AB  - BACKGROUND: Maharishi Amrit Kalash (MAK) is an herbal formulation composed of two
      herbal mixtures, MAK-4 and MAK-5. These preparations are part of a natural health
      care system from India, known as Maharishi Ayur-Veda. MAK-4 and MAK-5 are each
      composed of different herbs and are said to have maximum benefit when used in
      combination. This investigation evaluated the cancer inhibiting effects of MAK-4
      and MAK-5, in vitro and in vivo. METHODS: In vitro assays: Aqueous extracts of
      MAK-4 and MAK-5 were tested for effects on ras induced cell transformation in the
      Rat 6 cell line assessed by focus formation assay. In vivo assays: Urethane
      treated mice were put on a standard pellet diet or a diet supplemented with MAK
      4, MAK-5 or both. At 36 weeks, livers were examined for tumors, sera for oxygen
      radical absorbance capacity (ORAC), and liver homogenates for enzyme activities
      of glutathione peroxidase (GPX), glutathione-S-transferase (GST), and NAD(P)H:
      quinone reductase (QR). Liver fragments of MAK-fed mice were analyzed for
      connexin (cx) protein expression. RESULTS: MAK-5 and a combination of MAK-5 plus
      MAK-4, inhibited ras-induced cell transformation. In MAK-4, MAK-5 and MAK4+5
      treated mice we observed a 35%, 27% and 46% reduction in the development of
      urethane-induced liver nodules respectively. MAK-4 and MAK4+5-treated mice had a
      significantly higher ORAC value (P < 0.05) compared to controls (200.2 +/- 33.7
      and 191.6 +/- 32.2 vs. 152.2 +/- 15.7 ORAC units, respectively). The urethane
      treated MAK-4, MAK-5 and MAK4+5-fed mice had significantly higher activities of
      liver cytosolic enzymes compared to the urethane-treated controls and to
      untreated mice: GPX(0.23 +/- 0.08, 0.21 +/- 0.05, 0.25 +/- 0.04, 0.20 +/- 0.05,
      0.21 +/- 0.03 U/mg protein, respectively), GST (2.0 +/- 0.4, 2.0 +/- 0.6, 2.1 +/-
      0.3, 1.7 +/- 0.2, 1.7 +/- 0.2 U/mg protein, respectively) and QR (0.13 +/- 0.02,
      0.12 +/- 0.06, 0.15 +/- 0.03, 0.1 +/- 0.04, 0.11 +/- 0.03 U/mg protein,
      respectively). Livers of MAK-treated mice showed a time-dependent increased
      expression of cx32. CONCLUSION: Our results show that a MAK-supplemented diet
      inhibits liver carcinogenesis in urethane-treated mice. The prevention of
      excessive oxidative damage and the up-regulation of connexin expression are two
      of the possible effects of these products.

PMID- 17559640
TI  - MATLIGN: a motif clustering, comparison and matching tool.
AB  - BACKGROUND: Sequence motifs representing transcription factor binding sites
      (TFBS) are commonly encoded as position frequency matrices (PFM) or degenerate
      consensus sequences (CS). These formats are used to represent the characterised
      TFBS profiles stored in transcription factor databases, as well as to represent
      the potential motifs predicted using computational methods. To fill the gap
      between the known and predicted motifs, methods are needed for the post
      processing of prediction results, i.e. for matching, comparison and clustering of
      pre-selected motifs. The computational identification of over-represented motifs
      in sets of DNA sequences is, in particular, a task where post-processing can
      dramatically simplify the analysis. Efficient post-processing, for example,
      reduces the redundancy of the motifs predicted and enables them to be annotated.
      RESULTS: In order to facilitate the post-processing of motifs, in both PFM and CS
      formats, we have developed a tool called Matlign. The tool aligns and evaluates
      the similarity of motifs using a combination of scoring functions, and visualises
      the results using hierarchical clustering. By limiting the number of distinct
      gaps created (though, not their length), the alignment algorithm also correctly
      aligns motifs with an internal spacer. The method selects the best non-redundant
      motif set, with repetitive motifs merged together, by cutting the hierarchical
      tree using silhouette values. Our analyses show that Matlign can reliably
      discover the most similar analogue from a collection of characterised regulatory
      elements such that the method is also useful for the annotation of motif
      predictions by PFM library searches. CONCLUSION: Matlign is a user-friendly tool
      for post-processing large collections of DNA sequence motifs. Starting from a
      large number of potential regulatory motifs, Matlign provides a researcher with a
      non-redundant set of motifs, which can then be further associated to known
      regulatory elements. A web-server is available at
      http://ekhidna.biocenter.helsinki.fi/poxo/matlign.

PMID- 17559641
TI  - Increased standardized incidence ratio of breast cancer in female electronics
      workers.
AB  - BACKGROUND: In 1994, a hazardous waste site, polluted by the dumping of solvents
      from a former electronics factory, was discovered in Taoyuan, Taiwan. This
      subsequently emerged as a serious case of contamination through chlorinated
      hydrocarbons with suspected occupational cancer. The objective of this study was
      to determine if there was any increased risk of breast cancer among female
      workers in a 23-year follow-up period. METHODS: A total of 63,982 female workers
      were retrospectively recruited from the database of the Bureau of Labor Insurance
      (BLI) covering the period 1973-1997; the data were then linked with data, up to
      2001, from the National Cancer Registry at the Taiwanese Department of Health,
      from which standardized incidence ratios (SIRs) for different types of cancer
      were calculated as compared to the general population. RESULTS: There were a
      total of 286 cases of breast cancer, and after adjustment for calendar year and
      age, the SIR was close to 1. When stratified by the year 1974 (the year in which
      the regulations on solvent use were promulgated), the SIR of the cohort of
      workers who were first employed prior to 1974 increased to 1.38 (95% confidence
      interval, 1.11-1.70). No such trend was discernible for workers employed after
      1974. When 10 years of employment was considered, there was a further increase in
      the SIR for breast cancer, to 1.62. Those workers with breast cancer who were
      first employed prior to 1974 were employed at a younger age and for a longer
      period. Previous qualitative studies of interviews with the workers, corroborated
      by inspection records, showed a short-term high exposure to chlorinated alkanes
      and alkenes, particularly trichloroethylene before 1974. There were no similar
      findings on other types of cancer. CONCLUSION: Female workers with exposure to
      trichloroethylene and/or mixture of solvents, first employed prior to 1974, may
      have an excess risk of breast cancer.

PMID- 17559642
TI  - Identification and expression analysis of genes associated with bovine blastocyst
      formation.
AB  - BACKGROUND: Normal preimplantation embryo development encompasses a series of
      events including first cleavage division, activation of the embryonic genome,
      compaction and blastocyst formation. First lineage differentiation starts at the
      blastocyst stage with the formation of the trophectoderm and the inner cell mass.
      The main objective of this study was the detection, identification and expression
      analysis of genes associated with blastocyst formation in order to help us better
      understand this process. This information could lead to improvements of in vitro
      embryo production procedures. RESULTS: A subtractive cDNA library was constructed
      enriched for transcripts preferentially expressed at the blastocyst stage
      compared to the 2-cell and 8-cell stage. Sequence information was obtained for 65
      randomly selected clones. The RNA expression levels of 12 candidate genes were
      determined throughout 3 stages of preimplantation embryo development (2-cell, 8
      cell and blastocyst) and compared with the RNA expression levels of in vivo
      "golden standard" embryos using real-time PCR. The RNA expression profiles of 9
      (75%) transcripts (KRT18, FN1, MYL6, ATP1B3, FTH1, HINT1, SLC25A5, ATP6V0B,
      RPL10) were in agreement with the subtractive cDNA cloning approach, whereas for
      the remaining 3 (25%) (ACTN1, COPE, EEF1A1) the RNA expression level was equal or
      even higher at the earlier developmental stages compared to the blastocyst stage.
      Moreover, significant differences in RNA expression levels were observed between
      in vitro and in vivo produced embryos. By immunofluorescent labelling, the
      protein expression of KRT18, FN1 and MYL6 was determined throughout bovine
      preimplantation embryo development and showed the same pattern as the RNA
      expression analyses. CONCLUSION: By subtractive cDNA cloning, candidate genes
      involved in blastocyst formation were identified. For several candidate genes,
      important differences in gene expression were observed between in vivo and in
      vitro produced embryos, reflecting the influence of the in vitro culture system
      on the embryonic gene expression. Both RNA and protein expression analysis
      demonstrated that KRT18, FN1 and MYL6 are differentially expressed during
      preimplantation embryo development and those genes can be considered as markers
      for bovine blastocyst formation.

PMID- 17559644
TI  - In search of suitable reference genes for gene expression studies of human renal
      cell carcinoma by real-time PCR.
AB  - BACKGROUND: Housekeeping genes are commonly used as endogenous reference genes
      for the relative quantification of target genes in gene expression studies. No
      conclusive systematic study comparing the suitability of different candidate
      reference genes in clear cell renal cell carcinoma has been published to date. To
      remedy this situation, 10 housekeeping genes for normalizing purposes of RT-PCR
      measurements already recommended in various studies were examined with regard to
      their usefulness as reference genes. RESULTS: The expression of the potential
      reference genes was examined in matched malignant and non-malignant tissue
      specimens from 25 patients with clear cell renal cell carcinoma. Quality
      assessment of isolated RNA performed with a 2100 Agilent Bioanalyzer showed a
      mean RNA integrity number of 8.7 for all samples. The between-run variations
      related to the crossing points of PCR reactions of a control material ranged from
      0.17% to 0.38%. The expression of all genes did not depend on age, sex, and
      tumour stage. Except the genes TATA box binding protein (TBP) and peptidylprolyl
      isomerase A (PPIA), all genes showed significant differences in expression
      between malignant and non-malignant pairs. The expression stability of the
      candidate reference genes was additionally controlled using the software programs
      geNorm and NormFinder. TBP and PPIA were validated as suitable reference genes by
      normalizing the target gene ADAM9 using these two most stably expressed genes in
      comparison with up- and down-regulated housekeeping genes of the panel.
      CONCLUSION: Our study demonstrated the suitability of the two housekeeping genes
      PPIA and TBP as endogenous reference genes when comparing malignant tissue
      samples with adjacent normal tissue samples from clear cell renal cell carcinoma.
      Both genes are recommended as reference genes for relative gene quantification in
      gene profiling studies either as single gene or preferably in combination.

PMID- 17559643
TI  - A role for Insulin-like growth factor 2 in specification of the fast skeletal
      muscle fibre.
AB  - BACKGROUND: Fibre type specification is a poorly understood process beginning in
      embryogenesis in which skeletal muscle myotubes switch myosin-type to establish
      fast, slow and mixed fibre muscle groups with distinct function. Growth factors
      are required to establish slow fibres; it is unknown how fast twitch fibres are
      specified. Igf-2 is an embryonically expressed growth factor with established in
      vitro roles in skeletal muscle. Its localisation and role in embryonic muscle
      differentiation had not been established. RESULTS: Between E11.5 and E15.5 fast
      Myosin (FMyHC) localises to secondary myotubes evenly distributed throughout the
      embryonic musculature and gradually increasing in number so that by E15.5 around
      half contain FMyHC. The Igf-2 pattern closely correlates with FMyHC from E13.5
      and peaks at E15.5 when over 90% of FMyHC+ myotubes also contain Igf-2. Igf-2
      lags FMyHC and it is absent from muscle myotubes until E13.5. Igf-2 strongly down
      regulates by E17.5. A striking feature of the FMyHC pattern is its increased
      heterogeneity and attenuation in many fibres from E15.5 to day one after birth
      (P1). Transgenic mice (MIG) which express Igf-2 in all of their myotubes, have
      increased FMyHC staining, a higher proportion of FMyHC+ myotubes and loose their
      FMyHC staining heterogeneity. In Igf-2 deficient mice (MatDi) FMyHC+ myotubes are
      reduced to 60% of WT by E15.5. In vitro, MIG induces a 50% excess of FMyHC+ and a
      30% reduction of SMHyC+ myotubes in C2 cells which can be reversed by Igf-2
      targeted ShRNA resulting in 50% reduction of FMyHC. Total number of myotubes was
      not affected. CONCLUSION: In WT embryos the appearance of Igf-2 in embryonic
      myotubes lags FMyHC, but by E15.5 around 45% of secondary myotubes contain both
      proteins. Forced expression of Igf-2 into all myotubes causes an excess, and
      absence of Igf-2 suppresses, the FMyHC+ myotube component in both embryonic
      muscle and differentiated myoblasts. Igf-2 is thus required, not for initiating
      secondary myotube differentiation, but for establishing the correct proportion of
      FMyHC+ myotubes during fibre type specification (E15.5-P1). Since specific loss
      of FMyHC fibres is associated with many skeletal muscle pathologies these data
      have important medical implications.

PMID- 17559645
TI  - Optimization principles of dendritic structure.
AB  - BACKGROUND: Dendrites are the most conspicuous feature of neurons. However, the
      principles determining their structure are poorly understood. By employing cable
      theory and, for the first time, graph theory, we describe dendritic anatomy
      solely on the basis of optimizing synaptic efficacy with minimal resources.
      RESULTS: We show that dendritic branching topology can be well described by
      minimizing the path length from the neuron's dendritic root to each of its
      synaptic inputs while constraining the total length of wiring. Tapering of
      diameter toward the dendrite tip--a feature of many neurons--optimizes charge
      transfer from all dendritic synapses to the dendritic root while housekeeping the
      amount of dendrite volume. As an example, we show how dendrites of fly neurons
      can be closely reconstructed based on these two principles alone.

PMID- 17559646
TI  - Non-linear dimensionality reduction of signaling networks.
AB  - BACKGROUND: Systems wide modeling and analysis of signaling networks is essential
      for understanding complex cellular behaviors, such as the biphasic responses to
      different combinations of cytokines and growth factors. For example, tumor
      necrosis factor (TNF) can act as a proapoptotic or prosurvival factor depending
      on its concentration, the current state of signaling network and the presence of
      other cytokines. To understand combinatorial regulation in such systems, new
      computational approaches are required that can take into account non-linear
      interactions in signaling networks and provide tools for clustering,
      visualization and predictive modeling. RESULTS: Here we extended and applied an
      unsupervised non-linear dimensionality reduction approach, Isomap, to find
      clusters of similar treatment conditions in two cell signaling networks: (I)
      apoptosis signaling network in human epithelial cancer cells treated with
      different combinations of TNF, epidermal growth factor (EGF) and insulin and (II)
      combination of signal transduction pathways stimulated by 21 different ligands
      based on AfCS double ligand screen data. For the analysis of the apoptosis
      signaling network we used the Cytokine compendium dataset where activity and
      concentration of 19 intracellular signaling molecules were measured to
      characterise apoptotic response to TNF, EGF and insulin. By projecting the
      original 19-dimensional space of intracellular signals into a low-dimensional
      space, Isomap was able to reconstruct clusters corresponding to different
      cytokine treatments that were identified with graph-based clustering. In
      comparison, Principal Component Analysis (PCA) and Partial Least Squares -
      Discriminant analysis (PLS-DA) were unable to find biologically meaningful
      clusters. We also showed that by using Isomap components for supervised
      classification with k-nearest neighbor (k-NN) and quadratic discriminant analysis
      (QDA), apoptosis intensity can be predicted for different combinations of TNF,
      EGF and insulin. Prediction accuracy was highest when early activation time
      points in the apoptosis signaling network were used to predict apoptosis rates at
      later time points. Extended Isomap also outperformed PCA on the AfCS double
      ligand screen data. Isomap identified more functionally coherent clusters than
      PCA and captured more information in the first two-components. The Isomap
      projection performs slightly worse when more signaling networks are analyzed;
      suggesting that the mapping function between cues and responses becomes
      increasingly non-linear when large signaling pathways are considered. CONCLUSION:
      We developed and applied extended Isomap approach for the analysis of cell
      signaling networks. Potential biological applications of this method include
      characterization, visualization and clustering of different treatment conditions
      (i.e. low and high doses of TNF) in terms of changes in intracellular signaling
      they induce.

PMID- 17559648
TI  - Allelic association studies of genome wide association data can reveal errors in
      marker position assignments.
AB  - BACKGROUND: Genome wide association (GWA) studies provide the opportunity to
      develop new kinds of analysis. Analysing pairs of markers from separate regions
      might lead to the detection of allelic association which might indicate an
      interaction between nearby genes. METHODS: 396,591 markers typed in 541 subjects
      were studied. 7.8*1010 pairs of markers were screened and those showing initial
      evidence for allelic association were subjected to more thorough investigation
      along with 10 flanking markers on either side. RESULTS: No evidence was detected
      for interaction. However 6 markers appeared to have an incorrect map position
      according to NCBI Build 35. One of these was corrected in Build 36 and 2 were
      dropped. The remaining 3 were left with map positions inconsistent with their
      allelic association relationships. DISCUSSION: Although no interaction effects
      were detected the method was successful in identifying markers with probably
      incorrect map positions. CONCLUSION: The study of allelic association can
      supplement other methods for assigning markers to particular map positions.
      Analyses of this type may usefully be applied to data from future GWA studies.

PMID- 17559647
TI  - Marker tolerant, immunocompetent animals as a new tool for regenerative medicine
      and long-term cell tracking.
AB  - BACKGROUND: Immune-mediated rejection of labeled cells is a general problem in
      transplantation studies using cells labeled with any immunogenic marker, and also
      in gene therapy protocols. The aim of this study was to establish a syngeneic
      model for long-term histological cell tracking in the absence of immune-mediated
      rejection of labeled cells in immunocompetent animals. We used inbred transgenic
      Fischer 344 rats expressing human placental alkaline phosphatase (hPLAP) under
      the control of the ubiquitous R26 promoter for this study. hPLAP is an excellent
      marker enzyme, providing superb histological detection quality in paraffin and
      plastic sections. RESULTS: Transplantation of cells from hPLAP transgenic (hPLAP
      tg) F344 rats into wild-type (WT) F344 recipients failed because of immune
      mediated rejection. Here we show that this problem can be overcome by inducing
      tolerance to the marker gene by transplantation of bone marrow from hPLAP-tg F344
      rats into WT F344 hosts after lethal irradiation, or by neonatal exposure of WT
      F344 rats to hPLAP-tg F344 cells. As proof-of-principle, we injected bone marrow
      cells (BMC) from hPLAP-tg rats into the knee joint of marker tolerant, bone
      marrow-transplanted WT rats, and found successful engraftment and differentiation
      of donor cells. In addition, hPLAP-tg BMC injected intravenously in neonatally
      tolerized WT F344 hosts could be traced in lymph nodes, 2 months post-injection.
      CONCLUSION: In combination with the excellent marker hPLAP, marker tolerant
      animals may open up new perspectives for all experiments requiring long-term
      histological tracking of genetically labeled cells.

PMID- 17559649
TI  - Functional diversification of sonic hedgehog paralog enhancers identified by
      phylogenomic reconstruction.
AB  - BACKGROUND: Cis-regulatory modules of developmental genes are targets of
      evolutionary changes that underlie the morphologic diversity of animals. Little
      is known about the 'grammar' of interactions between transcription factors and
      cis-regulatory modules and therefore about the molecular mechanisms that underlie
      changes in these modules, particularly after gene and genome duplications. We
      investigated the ar-C midline enhancer of sonic hedgehog (shh) orthologs and
      paralogs from distantly related vertebrate lineages, from fish to human,
      including the basal vertebrate Latimeria menadoensis. RESULTS: We demonstrate
      that the sonic hedgehog a (shha) paralogs sonic hedgehog b (tiggy winkle
      hedgehog; shhb) genes of fishes have a modified ar-C enhancer, which specifies a
      diverged function at the embryonic midline. We have identified several conserved
      motifs that are indicative of putative transcription factor binding sites by
      local alignment of ar-C enhancers of numerous vertebrate sequences. To trace the
      evolutionary changes among paralog enhancers, phylogenomic reconstruction was
      carried out and lineage-specific motif changes were identified. The relation
      between motif composition and observed developmental differences was evaluated
      through transgenic functional analyses. Altering and exchanging motifs between
      paralog enhancers resulted in reversal of enhancer specificity in the floor plate
      and notochord. A model reconstructing enhancer divergence during vertebrate
      evolution was developed. CONCLUSION: Our model suggests that the identified
      motifs of the ar-C enhancer function as binary switches that are responsible for
      specific activity between midline tissues, and that these motifs are adjusted
      during functional diversification of paralogs. The unraveled motif changes can
      also account for the complex interpretation of activator and repressor input
      signals within a single enhancer.

PMID- 17559650
TI  - Prenatal diagnosis of a rare form of congenital mid-ureteral stricture: a case
      report and literature revisited.
AB  - BACKGROUND: Congenital mid-ureteral stricture is a rare malformation of the
      ureter leading to prenatal and neonatal hydronephrosis. Site characterization of
      the narrowing is important to optimize the surgical approach to the newborn
      affected by hydronephrosis. CASE PRESENTATION: We report a female EM with a rare
      form of hydronephrosis, (i.e. mid-ureteral stricture) which was detected early
      during pregnancy by imaging techniques. During fetal life both conventional fetal
      Ultrasound and maternal Magnetic Resonance Imaging (MRI) were used to diagnose
      the obstruction. Magnetic Resonance pyelography and retrograde Ureteropyelography
      were performed after delivery and before surgical correction and confirmed the
      finding.Furthermore, we revisited the literature using online MEDLINE and EMBASE
      databases. The literature reported only a few cases of prenatal diagnosis of
      early onset mid-ureteral stricture. CONCLUSION: Mid-ureteral stricture is a rare
      cause of prenatal hydronephrosis. The diagnosis should not be delayed in order to
      apply the appropriate surgical approach. As a result, we showed the usefulness of
      fetal MRI and postnatal Magnetic Resonance pyelography, in the event that
      radionuclide renography with Tc-MAG3 was less informative, to allow the detection
      of the site of ureteral narrowing. Intrasurgical retrograde ureteropyelography
      confirmed these findings.

PMID- 17559651
TI  - A quantitative RT-PCR platform for high-throughput expression profiling of 2500
      rice transcription factors.
AB  - BACKGROUND: Quantitative reverse transcription - polymerase chain reaction (qRT
      PCR) has been demonstrated to be particularly suitable for the analysis of weakly
      expressed genes, such as those encoding transcription factors. Rice (Oryza sativa
      L.) is an important crop and the most advanced model for monocotyledonous
      species; its nuclear genome has been sequenced and molecular tools are being
      developed for functional analyses. However, high-throughput methods for rice
      research are still limited and a large-scale qRT-PCR platform for gene expression
      analyses has not been reported. RESULTS: We established a qRT-PCR platform
      enabling the multi-parallel determination of the expression levels of more than
      2500 rice transcription factor genes. Additionally, using different rice
      cultivars, tissues and physiological conditions, we evaluated the expression
      stability of seven reference genes. We demonstrate this resource allows specific
      and reliable detection of the expression of transcription factor genes in rice.
      CONCLUSION: Multi-parallel qRT-PCR allows the versatile and sensitive
      transcriptome profiling of large numbers of rice transcription factor genes. The
      new platform complements existing microarray-based expression profiling
      techniques, by allowing the analysis of lowly expressed transcription factor
      genes to determine their involvement in developmental or physiological processes.
      We expect that this resource will be of broad utility to the scientific community
      in the further development of rice as an important model for plant science.

PMID- 17559652
TI  - Essential and non-essential DNA replication genes in the model halophilic
      Archaeon, Halobacterium sp. NRC-1.
AB  - BACKGROUND: Information transfer systems in Archaea, including many components of
      the DNA replication machinery, are similar to those found in eukaryotes.
      Functional assignments of archaeal DNA replication genes have been primarily
      based upon sequence homology and biochemical studies of replisome components, but
      few genetic studies have been conducted thus far. We have developed a tractable
      genetic system for knockout analysis of genes in the model halophilic archaeon,
      Halobacterium sp. NRC-1, and used it to determine which DNA replication genes are
      essential. RESULTS: Using a directed in-frame gene knockout method in
      Halobacterium sp. NRC-1, we examined nineteen genes predicted to be involved in
      DNA replication. Preliminary bioinformatic analysis of the large haloarchaeal
      Orc/Cdc6 family, related to eukaryotic Orc1 and Cdc6, showed five distinct clades
      of Orc/Cdc6 proteins conserved in all sequenced haloarchaea. Of ten orc/cdc6
      genes in Halobacterium sp. NRC-1, only two were found to be essential, orc10, on
      the large chromosome, and orc2, on the minichromosome, pNRC200. Of the three
      replicative-type DNA polymerase genes, two were essential: the chromosomally
      encoded B family, polB1, and the chromosomally encoded euryarchaeal-specific D
      family, polD1/D2 (formerly called polA1/polA2 in the Halobacterium sp. NRC-1
      genome sequence). The pNRC200-encoded B family polymerase, polB2, was non
      essential. Accessory genes for DNA replication initiation and elongation factors,
      including the putative replicative helicase, mcm, the eukaryotic-type DNA
      primase, pri1/pri2, the DNA polymerase sliding clamp, pcn, and the flap
      endonuclease, rad2, were all essential. Targeted genes were classified as non
      essential if knockouts were obtained and essential based on statistical analysis
      and/or by demonstrating the inability to isolate chromosomal knockouts except in
      the presence of a complementing plasmid copy of the gene. CONCLUSION: The results
      showed that ten out of nineteen eukaryotic-type DNA replication genes are
      essential for Halobacterium sp. NRC-1, consistent with their requirement for DNA
      replication. The essential genes code for two of ten Orc/Cdc6 proteins, two out
      of three DNA polymerases, the MCM helicase, two DNA primase subunits, the DNA
      polymerase sliding clamp, and the flap endonuclease.

PMID- 17559653
TI  - Do anesthetics and sampling strategies affect transcription analysis of fish
      tissues?
AB  - BACKGROUND: The aim of the current examination was to evaluate if sedation and
      anesthetic treatment techniques affect the quality of RNA extracted from liver,
      gill, head kidney and brain tissues in Atlantic salmon Salmo salar L. Blood
      parameters were measured and tissue specimens sampled in six groups of fish; one
      control group (0 minutes), two groups kept in pure seawater in 90 liter tanks for
      30 and 120 minutes, two groups treated with the anesthetic isoeugenol for 30 and
      120 minutes, and one group kept in pure seawater for 105 minutes and then
      anaesthetized with metacaine for 15 minutes. RNA quality was assessed with the
      NanoDrop ND-1000 spectrophotometer (260/280 and 260/230 nm ratios) and with the
      Agilent Bioanalyzer (28S/18S ratio and RIN data) in samples either preserved in
      liquefied nitrogen (N2) or in RNAlater. In addition, the transcriptional levels
      of two fast-responding genes were quantified in gill and brain tissues. RESULTS:
      The results show that physiological stress during sampling does not affect the
      quality of RNA extracted from fish specimens. However, prolonged sedation (2
      hours) resulted in a metabolic alkalosis that again affected the transcriptional
      levels of genes involved in ionoregulation and respiration. In gills, Na+-K+
      ATPase alpha1b was significantly downregulated and hypoxia inducible factor 1
      (HIF1) significantly upregulated after two hours of treatment with isoeugenol,
      suggesting that this commonly used sedative affects osmo-regulation and
      respiration in the fish. The results also suggest that for tissue preservation in
      general it is better to flash-freeze fish specimens in liquefied N2 than to use
      RNAlater. CONCLUSION: Prolonged sedation may affect the transcription of fast
      responding genes in tissues of fish. Two hours of sedation with isoeugenol
      resulted in downregulation of the Na+-K+-ATPase alpha1b gene and upregulation of
      the HIF1 gene in gills of Atlantic salmon. The quality of RNA extracted from
      tissue specimens, however, was not affected by sedation treatment. Flash-freezing
      of tissue specimens seems to be the preferred preservation technique, when
      sampling fish tissue specimens for RNA extraction.

PMID- 17559654
TI  - Identification of QTL controlling meat quality traits in an F2 cross between two
      chicken lines selected for either low or high growth rate.
AB  - BACKGROUND: Meat technological traits (i.e. meat pH, water retention and color)
      are important considerations for improving further processing of chicken meat.
      These quality traits were originally characterized in experimental lines selected
      for high (HG) and low (LG) growth. Presently, quantitative trait loci (QTL) for
      these traits were analyzed in an F2 population issued from the HG x LG cross. A
      total of 698 animals in 50 full-sib families were genotyped for 108
      microsatellite markers covering 21 linkage groups. RESULTS: The HG and LG birds
      exhibit large differences in body weight and abdominal fat content. Several meat
      quality traits [pH at 15 min post-slaughter (pH15) and ultimate pH (pHu), breast
      color-redness (BCo-R) and breast color-yellowness (BCo-Y)] were lower in HG
      chickens. In contrast, meat color-lightness (BCo-L) was higher in HG chickens,
      whereas meat drip loss (DL) was similar in both lines. HG birds were more active
      on the shackle line. Association analyses were performed using maximum-likelihood
      interval mapping in QTLMAP. Five genome-wide significant QTLs were revealed: two
      for pH15 on GGA1 and GGA2, one for DL on GGA1, one for BCo-R and one for BCo-Y
      both on GGA11. In addition, four suggestive QTLs were identified by QTLMAP for
      BCo-Y, pHu, pH15 and DL on GGA1, GGA4, GGA12 and GGA14, respectively. The QTL
      effects, averaged on heterozygous families, ranged from 12 to 31% of the
      phenotypic variance. Further analyses with QTLExpress confirmed the two genome
      wide QTLs for meat color on GGA11, failed to identify the genome-wide QTL for
      pH15 on GGA2, and revealed only suggestive QTLs for pH15 and DL on GGA1. However,
      QTLExpress qualified the QTL for pHu on GGA4 as genome-wide. CONCLUSION: The
      present study identified genome-wide significant QTLs for all meat technological
      traits presently assessed in these chickens, except for meat lightness. This
      study highlights the effects of divergent selection for growth rate on some
      behavioral traits, muscle biochemistry and ultimately meat quality traits.
      Several QTL regions were identified that are worthy of further characterization.
      Some QTLs may in fact co-localize, suggesting pleiotropic effects for some
      chromosomal regions.

PMID- 17559655
TI  - BK virus associated meningoencephalitis in an AIDS patient treated with HAART.
AB  - A severely immune-suppressed AIDS patient was suspected of suffering from BK
      virus (BKV) meningoencephalitis, after being studied for common causes of
      neurological complications of co-infectious origin. Polymerase chain reaction
      (PCR) and sequence analysis of cerebrospinal fluid and brain samples, confirmed
      the presence of BKV. His clinical condition improved along with the regression of
      brain lesions, after modifications on his antiretroviral regime. Five months
      after discharge, the patient was readmitted because of frequent headaches, and a
      marked inflammatory reaction was evidenced by a new magnetic resonance imaging
      (MRI). The symptoms paralleled a rising CD4+ lymphocyte count, and immune
      reconstitution syndrome was suspected. This is the first non-postmortem report of
      BKV meningoencephalitis in an AIDS patient, showing clinical and radiographic
      improvement solely under HAART.

PMID- 17559656
TI  - Lens stem cells may reside outside the lens capsule: an hypothesis.
AB  - In this paper, we consider the ocular lens in the context of contemporary
      developments in biological ideas. We attempt to reconcile lens biology with stem
      cell concepts and a dearth of lens tumors.Historically, the lens has been viewed
      as a closed system, in which cells at the periphery of the lens epithelium
      differentiate into fiber cells. Theoretical considerations led us to question
      whether the intracapsular lens is indeed self-contained. Since stem cells
      generate tumors and the lens does not naturally develop tumors, we reasoned that
      lens stem cells may not be present within the capsule. We hypothesize that lens
      stem cells reside outside the lens capsule, in the nearby ciliary body. Our ideas
      challenge the existing lens biology paradigm. We begin our discussion with lens
      background information, in order to describe our lens stem cell hypothesis in the
      context of published data. Then we present the ciliary body as a possible source
      for lens stem cells, and conclude by comparing the ocular lens with the corneal
      epithelium.

PMID- 17559657
TI  - Common molecular pathways involved in human CD133+/CD34+ progenitor cell
      expansion and cancer.
AB  - BACKGROUND: Uncovering the molecular mechanism underlying expansion of
      hematopoietic stem and progenitor cells is critical to extend current therapeutic
      applications and to understand how its deregulation relates to leukemia. The
      characterization of genes commonly relevant to stem/progenitor cell expansion and
      tumor development should facilitate the identification of novel therapeutic
      targets in cancer. METHODS: CD34+/CD133+ progenitor cells were purified from
      human umbilical cord blood and expanded in vitro. Correlated molecular changes
      were analyzed by gene expression profiling using microarrays covering up to
      55,000 transcripts. Genes regulated during progenitor cell expansion were
      identified and functionally classified. Aberrant expression of such genes in
      cancer was indicated by in silico SAGE. Differential expression of selected genes
      was assessed by real-time PCR in hematopoietic cells from chronic myeloid
      leukemia patients and healthy individuals. RESULTS: Several genes and signaling
      pathways not previously associated with ex vivo expansion of CD133+/CD34+ cells
      were identified, most of which associated with cancer. Regulation of MEK/ERK and
      Hedgehog signaling genes in addition to numerous proto-oncogenes was detected
      during conditions of enhanced progenitor cell expansion. Quantitative real-time
      PCR analysis confirmed down-regulation of several newly described cancer
      associated genes in CD133+/CD34+ cells, including DOCK4 and SPARCL1 tumor
      suppressors, and parallel results were verified when comparing their expression
      in cells from chronic myeloid leukemia patients CONCLUSION: Our findings reveal
      potential molecular targets for oncogenic transformation in CD133+/CD34+ cells
      and strengthen the link between deregulation of stem/progenitor cell expansion
      and the malignant process.

PMID- 17559658
TI  - Can Clustal-style progressive pairwise alignment of multiple sequences be used in
      RNA secondary structure prediction?
AB  - BACKGROUND: In ribonucleic acid (RNA) molecules whose function depends on their
      final, folded three-dimensional shape (such as those in ribosomes or spliceosome
      complexes), the secondary structure, defined by the set of internal basepair
      interactions, is more consistently conserved than the primary structure, defined
      by the sequence of nucleotides. RESULTS: The research presented here investigates
      the possibility of applying a progressive, pairwise approach to the alignment of
      multiple RNA sequences by simultaneously predicting an energy-optimized consensus
      secondary structure. We take an existing algorithm for finding the secondary
      structure common to two RNA sequences, Dynalign, and alter it to align profiles
      of multiple sequences. We then explore the relative successes of different
      approaches to designing the tree that will guide progressive alignments of
      sequence profiles to create a multiple alignment and prediction of conserved
      structure. CONCLUSION: We have found that applying a progressive, pairwise
      approach to the alignment of multiple ribonucleic acid sequences produces highly
      reliable predictions of conserved basepairs, and we have shown how these
      predictions can be used as constraints to improve the results of a single
      sequence structure prediction algorithm. However, we have also discovered that
      the amount of detail included in a consensus structure prediction is highly
      dependent on the order in which sequences are added to the alignment (the guide
      tree), and that if a consensus structure does not have sufficient detail, it is
      less likely to provide useful constraints for the single-sequence method.

PMID- 17559659
TI  - Stent versus gastrojejunostomy for the palliation of gastric outlet obstruction:
      a systematic review.
AB  - BACKGROUND: Gastrojejunostomy (GJJ) is the most commonly used palliative
      treatment modality for malignant gastric outlet obstruction. Recently, stent
      placement has been introduced as an alternative treatment. We reviewed the
      available literature on stent placement and GJJ for gastric outlet obstruction,
      with regard to medical effects and costs. METHODS: A systematic review of the
      literature was performed by searching PubMed for the period January 1996 and
      January 2006. A total of 44 publications on GJJ and stents was identified and
      reported results on medical effects and costs were pooled and evaluated. Results
      from randomized and comparative studies were used for calculating odds ratios
      (OR) to compare differences between the two treatment modalities. RESULTS: In 2
      randomized trials, stent placement was compared with GJJ (with 27 and 18 patients
      in each trial). In 6 comparative studies, stent placement was compared with GJJ.
      Thirty-six series evaluated either stent placement or GJJ. A total of 1046
      patients received a duodenal stent and 297 patients underwent GJJ. No differences
      between stent placement and gastrojejunostomy were found in technical success
      (96% vs. 100%), early and late major complications 7% vs. 6% and 18% vs. 17%,
      respectively) and persisting symptoms (8% vs. 9%). Initial clinical success was
      higher after stent placement (89% vs. 72%). Minor complications were less
      frequently seen after stent placement in the patient series (9% vs. 33%), however
      the pooled analysis showed no differences (OR: 0.75, p = 0.8). Recurrent
      obstructive symptoms were more common after stent placement (18% vs. 1%).
      Hospital stay was prolonged after GJJ compared to stent placement (13 days vs. 7
      days). The mean survival was 105 days after stent placement and 164 days after
      GJJ. CONCLUSION: These results suggest that stent placement may be associated
      with more favorable results in patients with a relatively short life expectancy,
      while GJJ is preferable in patients with a more prolonged prognosis. The paucity
      of evidence from large randomized trials may however have influenced the results
      and therefore a trial of sufficient size is needed to determine which palliative
      treatment modality is optimal in (sub)groups of patients with malignant gastric
      outlet obstruction.

PMID- 17559660
TI  - Prevalence of chronic fatigue syndrome in metropolitan, urban, and rural Georgia.
AB  - BACKGROUND: Chronic fatigue syndrome (CFS) is a debilitating illness with no
      known cause or effective therapy. Population-based epidemiologic data on CFS
      prevalence are critical to put CFS in a realistic context for public health
      officials and others responsible for allocating resources. METHODS: Based on a
      random-digit dialing survey we ascertained CFS cases and controls to estimate the
      prevalence of CFS in metropolitan, urban, and rural populations of Georgia. This
      report focuses on the 5,623 of 19,381 respondents ages 18 to 59 years old.
      Fatigued (2,438), randomly selected unwell not fatigued (1,429) and randomly
      selected well (1,756) respondents completed telephone questionnaires concerning
      fatigue, other symptoms, and medical history. Subsets of those identified by
      interview as having CFS-like illness (292), chronic unwellness which was not CFS
      like (268 - randomly selected), and well subjects (223, matched to those with CFS
      like illness on sex, race, and age) completed a clinical evaluation. RESULTS: We
      estimated that 2.54% of persons 18 to 59 years of age suffered from CFS. There
      were no significant differences in prevalence of CFS between metropolitan, urban
      or rural populations or between white and black residents of the three regions.
      However, there were significant differences in female-to-male ratios of
      prevalence across the strata (metropolitan female: male 11.2 : 1, urban 1.7 : 1,
      rural 0.8 : 1). CONCLUSION: We estimated that 2.54% of the Georgia population
      suffers from CFS, which is 6- to 10-fold higher than previous population-based
      estimates in other geographic areas. These differences may reflect broader
      screening criteria and differences in the application of the case definition.
      However, we cannot exclude the possibility that CFS prevalence may be higher in
      Georgia than other areas where it has been measured. Although the study did not
      identify differences in overall prevalence between metropolitan, urban, and rural
      Georgia populations, it did suggest the need for additional stratified analyses
      by geographic strata.

PMID- 17559661
TI  - How common is chronic fatigue syndrome; how long is a piece of string?

PMID- 17559662
TI  - Identification of regulatory network topological units coordinating the genome
      wide transcriptional response to glucose in Escherichia coli.
AB  - BACKGROUND: Glucose is the preferred carbon and energy source for Escherichia
      coli. A complex regulatory network coordinates gene expression, transport and
      enzyme activities in response to the presence of this sugar. To determine the
      extent of the cellular response to glucose, we applied an approach combining
      global transcriptome and regulatory network analyses. RESULTS: Transcriptome data
      from isogenic wild type and crp- strains grown in Luria-Bertani medium (LB) or LB
      + 4 g/L glucose (LB+G) were analyzed to identify differentially transcribed
      genes. We detected 180 and 200 genes displaying increased and reduced relative
      transcript levels in the presence of glucose, respectively. The observed
      expression pattern in LB was consistent with a gluconeogenic metabolic state
      including active transport and interconversion of small molecules and
      macromolecules, induction of protease-encoding genes and a partial heat shock
      response. In LB+G, catabolic repression was detected for transport and metabolic
      interconversion activities. We also detected an increased capacity for de novo
      synthesis of nucleotides, amino acids and proteins. Cluster analysis of a subset
      of genes revealed that CRP mediates catabolite repression for most of the genes
      displaying reduced transcript levels in LB+G, whereas Fis participates in the
      upregulation of genes under this condition. An analysis of the regulatory
      network, in terms of topological functional units, revealed 8 interconnected
      modules which again exposed the importance of Fis and CRP as directly responsible
      for the coordinated response of the cell. This effect was also seen with other
      not extensively connected transcription factors such as FruR and PdhR, which
      showed a consistent response considering media composition. CONCLUSION: This work
      allowed the identification of eight interconnected regulatory network modules
      that includes CRP, Fis and other transcriptional factors that respond directly or
      indirectly to the presence of glucose. In most cases, each of these modules
      includes genes encoding physiologically related functions, thus indicating a
      connection between regulatory network topology and related cellular functions
      involved in nutrient sensing and metabolism.

PMID- 17559663
TI  - An animated depiction of major depression epidemiology.
AB  - BACKGROUND: Epidemiologic estimates are now available for a variety of parameters
      related to major depression epidemiology (incidence, prevalence, etc.). These
      estimates are potentially useful for policy and planning purposes, but it is
      first necessary that they be synthesized into a coherent picture of the
      epidemiology of the condition. Several attempts to do so have been made using
      mathematical modeling procedures. However, this information is not easy to
      communicate to users of epidemiological data (clinicians, administrators, policy
      makers). METHODS: In this study, up-to-date data on major depression epidemiology
      were integrated using a discrete event simulation model. The mathematical model
      was animated in Virtual Reality Modeling Language (VRML) to create a visual,
      rather than mathematical, depiction of the epidemiology. RESULTS: Consistent with
      existing literature, the model highlights potential advantages of population
      health strategies that emphasize access to effective long-term treatment. The
      paper contains a web-link to the animation. CONCLUSION: Visual animation of
      epidemiological results may be an effective knowledge translation tool. In
      clinical practice, such animations could potentially assist with patient
      education and enhanced long-term compliance.

PMID- 17559664
TI  - Zac1 functions through TGFbetaII to negatively regulate cell number in the
      developing retina.
AB  - BACKGROUND: Organs are programmed to acquire a particular size during
      development, but the regulatory mechanisms that dictate when dividing progenitor
      cells should permanently exit the cell cycle and stop producing additional
      daughter cells are poorly understood. In differentiated tissues, tumor suppressor
      genes maintain a constant cell number and intact tissue architecture by
      controlling proliferation, apoptosis and cell dispersal. Here we report a similar
      role for two tumor suppressor genes, the Zac1 zinc finger transcription factor
      and that encoding the cytokine TGFbetaII, in the developing retina. RESULTS:
      Using loss and gain-of-function approaches, we show that Zac1 is an essential
      negative regulator of retinal size. Zac1 mutants develop hypercellular retinae
      due to increased progenitor cell proliferation and reduced apoptosis at late
      developmental stages. Consequently, supernumerary rod photoreceptors and amacrine
      cells are generated, the latter of which form an ectopic cellular layer, while
      other retinal cells are present in their normal number and location. Strikingly,
      Zac1 functions as a direct negative regulator of a rod fate, while acting cell
      non-autonomously to modulate amacrine cell number. We implicate TGFbetaII,
      another tumor suppressor and cytokine, as a Zac1-dependent amacrine cell negative
      feedback signal. TGFbetaII and phospho-Smad2/3, its downstream effector, are
      expressed at reduced levels in Zac1 mutant retinae, and exogenous TGFbetaII
      relieves the mutant amacrine cell phenotype. Moreover, treatment of wild-type
      retinae with a soluble TGFbeta inhibitor and TGFbeta receptor II (TGFbetaRII)
      conditional mutants generate excess amacrine cells, phenocopying the Zac1 mutant
      phenotype. CONCLUSION: We show here that Zac1 has an essential role in cell
      number control during retinal development, akin to its role in tumor surveillance
      in mature tissues. Furthermore, we demonstrate that Zac1 employs a novel cell non
      autonomous strategy to regulate amacrine cell number, acting in cooperation with
      a second tumor suppressor gene, TGFbetaII, through a negative feedback pathway.
      This raises the intriguing possibility that tumorigenicity may also be associated
      with the loss of feedback inhibition in mature tissues.

PMID- 17559665
TI  - Downregulation of selective microRNAs in trigeminal ganglion neurons following
      inflammatory muscle pain.
AB  - Active regulation of gene expression in the nervous system plays an important
      role in the development and/or maintenance of inflammatory pain. MicroRNA (miRNA)
      negatively regulates gene expression via posttranscriptional or transcriptional
      inhibition of specific genes. To explore the possible involvement of miRNA in
      gene regulation during inflammatory pain, we injected complete Freund's adjuvant
      (CFA) unilaterally into the rat masseter muscle and quantified changes in neuron
      specific mature miRNAs in the trigeminal ganglion (TG). Real-time reverse
      transcription polymerase chain reaction revealed significant, but differential,
      downregulation of mature miR-10a, -29a, -98, -99a, -124a, -134, and -183 in the
      ipsilateral mandibular division (V3) of the TG within 4 hr after CFA. In
      contrast, levels of tested miRNAs did not change significantly in the
      contralateral V3 or the ipsilateral ophthalmic and maxillary divisions of the TG
      from inflamed rats, nor in the ipsilateral V3 of saline-injected animals. The
      downregulated miRNAs recovered differentially to a level equal to or higher than
      that in naive animals. Full recovery time varied with miRNA species but was at
      least 4 days. Expression and downregulation of some miRNAs were further confirmed
      by in situ hybridization of TG neurons that innervate the inflamed muscle.
      Although neurons of all sizes expressed these miRNAs, their signals varied
      between neurons. Our results indicate that miRNA species specific to neurons are
      quickly regulated following inflammatory muscle pain.

PMID- 17559666
TI  - Bio::NEXUS: a Perl API for the NEXUS format for comparative biological data.
AB  - BACKGROUND: Evolutionary analysis provides a formal framework for comparative
      analysis of genomic and other data. In evolutionary analysis, observed data are
      treated as the terminal states of characters that have evolved (via transitions
      between states) along the branches of a tree. The NEXUS standard of Maddison, et
      al. (1997; Syst. Biol. 46: 590-621) provides a portable, expressive and flexible
      text format for representing character-state data and trees. However, due to its
      complexity, NEXUS is not well supported by software and is not easily accessible
      to bioinformatics users and developers. RESULTS: Bio::NEXUS is an application
      programming interface (API) implemented in Perl, available from CPAN and
      SourceForge. The 22 Bio::NEXUS modules define 351 methods in 4229 lines of code,
      with 2706 lines of POD (Plain Old Documentation). Bio::NEXUS provides an object
      oriented interface to reading, writing and manipulating the contents of NEXUS
      files. It closely follows the extensive explanation of the NEXUS format provided
      by Maddison et al., supplemented with a few extensions such as support for the
      NHX (New Hampshire Extended) tree format. CONCLUSION: In spite of some
      limitations owing to the complexity of NEXUS files and the lack of a formal
      grammar, NEXUS will continue to be useful for years to come. Bio::NEXUS provides
      a user-friendly API for NEXUS supplemented with an extensive set of methods for
      manipulations such as re-rooting trees and selecting subsets of data. Bio::NEXUS
      can be used as glue code for connecting existing software that uses NEXUS, or as
      a framework for new applications.

PMID- 17559667
TI  - Additive risk survival model with microarray data.
AB  - BACKGROUND: Microarray techniques survey gene expressions on a global scale.
      Extensive biomedical studies have been designed to discover subsets of genes that
      are associated with survival risks for diseases such as lymphoma and construct
      predictive models using those selected genes. In this article, we investigate
      simultaneous estimation and gene selection with right censored survival data and
      high dimensional gene expression measurements. RESULTS: We model the survival
      time using the additive risk model, which provides a useful alternative to the
      proportional hazards model and is adopted when the absolute effects, instead of
      the relative effects, of multiple predictors on the hazard function are of
      interest. A Lasso (least absolute shrinkage and selection operator) type estimate
      is proposed for simultaneous estimation and gene selection. Tuning parameter is
      selected using the V-fold cross validation. We propose Leave-One-Out cross
      validation based methods for evaluating the relative stability of individual
      genes and overall prediction significance. CONCLUSION: We analyze the MCL and
      DLBCL data using the proposed approach. A small number of probes represented on
      the microarrays are identified, most of which have sound biological implications
      in lymphoma development. The selected probes are relatively stable and the
      proposed approach has overall satisfactory prediction power.

PMID- 17559668
TI  - Screen time and physical activity during adolescence: longitudinal effects on
      obesity in young adulthood.
AB  - BACKGROUND: The joint impact of sedentary behavior and physical activity on
      obesity has not been assessed in a large cohort followed from adolescence to
      adulthood. METHODS: Nationally representative longitudinal data from Waves II
      (1995; mean age: 15.9) and III (2001; mean age: 21.4) of the National
      Longitudinal Study of Adolescent Health (n = 9,155) were collected. Sex
      stratified multivariate logistic regression analysis assessed the odds of obesity
      associated with Wave II MVPA and screen time, controlling for sociodemographic
      characteristics and change in MVPA and screen time from Wave II to III. Obesity
      was defined using body mass index (BMI, kg/m2) International Obesity Task Force
      cut-points at Wave II and adult cut-points at Wave III (BMI >or= 30). RESULTS: In
      males, adjusted odds of prevalent obesity was strongly predicted by MVPA bouts
      [OR (95% CI): OR6 vs. 1 MVPA bouts = 0.50 (0.40, 0.62); OR4 vs. 40 hrs screen
      time = 0.83 (0.69, 1.00)]. In females, greater MVPA bouts and lower screen time
      correlated with lower prevalent obesity [OR (95% CI): OR6 vs. 1 MVPA bouts = 0.67
      (0.49, 0.91); OR4 vs. 40 hrs screen time = 0.67 (0.53, 0.85)]. Longitudinally,
      adolescent screen time hours had a stronger influence on incident obesity in
      females [OR (95% CI): OR4 vs. 40 hrs = 0.58 (0.43, 0.80)] than males [OR (95%
      CI): OR4 vs. 40 hrs = 0.78 (0.61, 0.99)]. Longitudinal activity patterns were not
      predictive of incident obesity. CONCLUSION: Reducing screen time during
      adolescence and into adulthood may be a promising strategy for reducing obesity
      incidence, especially in females.

PMID- 17559669
TI  - Comparison of morning versus afternoon cecal intubation rates.
AB  - BACKGROUND: Many factors impacting cecal intubation rates have been examined in
      detail; however, little information exists regarding the effect of the timing of
      the procedure. We sought to examine any difference in cecal intubation rates
      between morning and afternoon colonoscopies and identify factors contributing to
      a discrepancy. METHODS: Retrospective, single-center study comparing cecal
      intubation rates for colonoscopies performed in the morning (begun prior to 12
      noon) and colonoscopies performed in the afternoon (begun after 12 noon) over an
      approximately 12 month period. Univariate and multivariate analyses were
      performed evaluating patient demographics, procedure indication(s), endoscopist,
      bowel preparation type and quality, and participation by a gastroenterology
      fellow. RESULTS: 6087 colonoscopies were evaluated in this study. Colonoscopies
      (n = 3729) performed in the morning were compared to colonoscopies performed in
      the afternoon (n = 2358). The crude completion rate to the cecum was 95.0% in the
      morning group while the completion rate to the cecum was 93.6% of the afternoon
      exams (p = 0.02). The morning colonoscopies had better bowel preparation quality
      (p < 0.001). The multivariate analyses demonstrated that gender, age, and bowel
      preparation quality impacted completion rates. After correcting for these
      factors, there was no significant difference in completion rates in the morning
      versus afternoon. CONCLUSION: Uncorrected cecal intubation rates were lower in
      the afternoon compared to the morning in outpatients undergoing colonoscopy.
      Bowel preparation quality was worse in the afternoon compared with the morning.
      Efforts at improving afternoon bowel preparation may improve the outcome of
      afternoon colonoscopies.

PMID- 17559670
TI  - Medication beliefs among patients with inflammatory bowel disease who report low
      quality of life: a qualitative study.
AB  - BACKGROUND: Non-adherence to drug therapy is common in Inflammatory Bowel Disease
      (IBD). Patients' beliefs about treatment have an important influence on
      adherence. An in-depth understanding of this area is, therefore, important for
      patient-centred care. The aim of the study was to assess patients' perspectives
      and beliefs about their medication and to determine how this relates to medicine
      taking and other related health behaviour as part of a larger qualitative study
      on health care related behaviour in patients with IBD. METHODS: Individual semi
      structured interviews and focus groups. An iterative approach following
      principles of grounded theory was applied to data collection and analysis.
      RESULTS: Main emerging themes were: balance of perceived necessity versus
      concerns, perceived impact of symptoms and willingness to self-manage medication.
      There was a clear distinction made between steroids and other preparations.
      Concerns included the fear of both short and long-term side-effects (mainly
      steroids), uncertainties about drug interactions and development of long-term
      immunity. Adapting to and accepting medication use was linked to acceptance of
      IBD. CONCLUSION: A concordant approach including flexible and pro-active support
      as well as accurate information is important in assisting patients with IBD to
      self-manage their medication effectively. Health professionals should be aware
      that attitudes to medicine taking and other related behaviours may be medicine
      specific and change over time.

PMID- 17559671
TI  - Computational prediction of Pho regulons in cyanobacteria.
AB  - BACKGROUND: Phosphorus is an essential element for all life forms. However, it is
      limiting in most ecological environments where cyanobacteria inhabit. Elucidation
      of the phosphorus assimilation pathways in cyanobacteria will further our
      understanding of the physiology and ecology of this important group of
      microorganisms. However, a systematic study of the Pho regulon, the core of the
      phosphorus assimilation pathway in a cyanobacterium, is hitherto lacking.
      RESULTS: We have predicted and analyzed the Pho regulons in 19 sequenced
      cyanobacterial genomes using a highly effective scanning algorithm that we have
      previously developed. Our results show that different cyanobacterial
      species/ecotypes may encode diverse sets of genes responsible for the utilization
      of various sources of phosphorus, ranging from inorganic phosphate,
      phosphodiester, to phosphonates. Unlike in E. coli, some cyanobacterial genes
      that are directly involved in phosphorus assimilation seem to not be under the
      regulation of the regulator SphR (orthologue of PhoB in E coli.) in some
      species/ecotypes. On the other hand, SphR binding sites are found for genes known
      to play important roles in other biological processes. These genes might serve as
      bridging points to coordinate the phosphorus assimilation and other biological
      processes. More interestingly, in three cyanobacterial genomes where no sphR gene
      is encoded, our results show that there is virtually no functional SphR binding
      site, suggesting that transcription regulators probably play an important role in
      retaining their binding sites. CONCLUSION: The Pho regulons in cyanobacteria are
      highly diversified to accommodate to their respective living environments. The
      phosphorus assimilation pathways in cyanobacteria are probably tightly coupled to
      a number of other important biological processes. The loss of a regulator may
      lead to the rapid loss of its binding sites in a genome.

PMID- 17559672
TI  - Activation of Akt is increased in the dysplasia-carcinoma sequence in Barrett's
      oesophagus and contributes to increased proliferation and inhibition of
      apoptosis: a histopathological and functional study.
AB  - BACKGROUND: The incidence of oesophageal adenocarcinoma is increasing rapidly in
      the developed world. The serine-threonine protein kinase and proto-oncogene Akt
      has been reported to regulate proliferation and apoptosis in several tissues but
      there are no data on the involvement of Akt in oesophageal carcinogenesis.
      Therefore we have examined the activation of Akt in Barrett's oesophagus and
      oesophageal adenocarcinoma and the functional effects of Akt activation in vitro.
      METHODS: Expression of total and active (phosphorylated) Akt were determined in
      endoscopic biopsies and surgical resection specimens using immunohistochemistry.
      The functional effects of Akt were examined using Barrett's adenocarcinoma cells
      in culture. RESULTS: In normal squamous oesophagus, erosive oesophagitis and non
      dysplastic Barrett's oesophagus, phospho-Akt was limited to the basal 1/3 of the
      mucosa. Image analysis confirmed that Akt activation was significantly increased
      in non-dysplastic Barrett's oesophagus compared to squamous epithelium and
      further significantly increased in high-grade dysplasia and adenocarcinoma. In
      all cases of high grade dysplasia and adenocarcinoma Akt was activated in the
      luminal 1/3 of the epithelium. Transient acid exposure and the obesity hormone
      leptin activated Akt, stimulated proliferation and inhibited apoptosis: the
      combination of acid and leptin was synergistic. Inhibition of Akt phosphorylation
      with LY294002 increased apoptosis and blocked the effects of acid and leptin both
      alone and in combination. Activation of Akt was associated with downstream
      phosphorylation and deactivation of the pro-apoptotic protein Bad and
      phosphorylation of the Forkhead family transcription factor FOXO1. CONCLUSION:
      Akt is abnormally activated in Barrett's oesophagus, high grade dysplasia and
      adenocarcinoma. Akt activation promotes proliferation and inhibits apoptosis in
      Barrett's adenocarcinoma cells and both transient acid exposure and leptin
      stimulate Akt phosphorylation. Downstream targets of Akt include Bad and Forkhead
      transcription factors. Activation of Akt in obesity and by reflux of gastric acid
      may be important in the pathogenesis of Barrett's adenocarcinoma.

PMID- 17559673
TI  - HIV-1 Vpr activates the G2 checkpoint through manipulation of the ubiquitin
      proteasome system.
AB  - HIV-1 Vpr is a viral accessory protein that activates ATR through the induction
      of DNA replication stress. ATR activation results in cell cycle arrest in G2 and
      induction of apoptosis. In the present study, we investigate the role of the
      ubiquitin/proteasome system (UPS) in the above activity of Vpr. We report that
      the general function of the UPS is required for Vpr to induce G2 checkpoint
      activation, as incubation of Vpr-expressing cells with proteasome inhibitors
      abolishes this effect. We further investigated in detail the specific E3
      ubiquitin ligase subunits that Vpr manipulates. We found that Vpr binds to the
      DCAF1 subunit of a cullin 4a/DDB1 E3 ubiquitin ligase. The carboxy-terminal
      domain Vpr(R80A) mutant, which is able to bind DCAF1, is inactive in checkpoint
      activation and has dominant-negative character. In contrast, the mutation Q65R,
      in the leucine-rich domain of Vpr that mediates DCAF1 binding, results in an
      inactive Vpr devoid of dominant negative behavior. Thus, the interaction of Vpr
      with DCAF1 is required, but not sufficient, for Vpr to cause G2 arrest. We
      propose that Vpr recruits, through its carboxy terminal domain, an unknown
      cellular factor that is required for G2-to-M transition. Recruitment of this
      factor leads to its ubiquitination and degradation, resulting in failure to enter
      mitosis.

PMID- 17559674
TI  - Regulation of the JNK pathway by TGF-beta activated kinase 1 in rheumatoid
      arthritis synoviocytes.
AB  - c-Jun N-terminal kinase (JNK) contributes to metalloproteinase (MMP) gene
      expression and joint destruction in inflammatory arthritis. It is phosphorylated
      by at least two upstream kinases, the mitogen-activated protein kinase kinases
      (MEK) MKK4 and MKK7, which are, in turn, phosphorylated by MEK kinases (MEKKs).
      However, the MEKKs that are most relevant to JNK activation in synoviocytes have
      not been determined. These studies were designed to assess the hierarchy of
      upstream MEKKs, MEKK1, MEKK2, MEKK3, and transforming growth factor-beta
      activated kinase (TAK)1, in rheumatoid arthritis (RA). Using either small
      interfering RNA (siRNA) knockdown or knockout fibroblast-like synoviocytes
      (FLSs), MEKK1, MEKK2, or MEKK3 deficiency (either alone or in combination) had no
      effect on IL-1beta-stimulated phospho-JNK (P-JNK) induction or MMP expression.
      However, TAK1 deficiency significantly decreased P-JNK, P-MKK4 and P-MKK7
      induction compared with scrambled control. TAK1 knockdown did not affect p38
      activation. Kinase assays showed that TAK1 siRNA significantly suppressed JNK
      kinase function. In addition, MKK4 and MKK7 kinase activity were significantly
      decreased in TAK1 deficient FLSs. Electrophoretic mobility shift assays
      demonstrated a significant decrease in IL-1beta induced AP-1 activation due to
      TAK1 knockdown. Quantitative PCR showed that TAK1 deficiency significantly
      decreased IL-1beta-induced MMP3 gene expression and IL-6 protein expression.
      These results show that TAK1 is a critical pathway for IL-1beta-induced
      activation of JNK and JNK-regulated gene expression in FLSs. In contrast to other
      cell lineages, MEKK1, MEKK2, and MEKK3 did not contribute to JNK phosphorylation
      in FLSs. The data identify TAK1 as a pivotal upstream kinase and potential
      therapeutic target to modulate synoviocyte activation in RA.

PMID- 17559675
TI  - In silico screening of mutational effects on enzyme-proteic inhibitor affinity: a
      docking-based approach.
AB  - BACKGROUND: Molecular recognition between enzymes and proteic inhibitors is
      crucial for normal functioning of many biological pathways. Mutations in either
      the enzyme or the inhibitor protein often lead to a modulation of the binding
      affinity with no major alterations in the 3D structure of the complex. RESULTS:
      In this study, a rigid body docking-based approach has been successfully probed
      in its ability to predict the effects of single and multiple point mutations on
      the binding energetics in three enzyme-proteic inhibitor systems. The only
      requirement of the approach is an accurate structural model of the complex
      between the wild type forms of the interacting proteins, with the assumption that
      the architecture of the mutated complexes is almost the same as that of the wild
      type and no major conformational changes occur upon binding. The method was
      applied to 23 variants of the ribonuclease inhibitor-angiogenin complex, to 15
      variants of the barnase-barstar complex, and to 8 variants of the bovine
      pancreatic trypsin inhibitor-beta Trypsin system, leading to thermodynamic and
      kinetic estimates consistent with in vitro data. Furthermore, simulations with
      and without explicit water molecules at the protein-protein interface suggested
      that they should be included in the simulations only when their positions are
      well defined both in the wild type and in the mutants and they result to be
      relevant for the modulation of mutational effects on the association process.
      CONCLUSION: The correlative models built in this study allow for predictions of
      mutational effects on the thermodynamics and kinetics of association of three
      substantially different systems, and represent important extensions of our
      computational approach to cases in which it is not possible to estimate the
      absolute free energies. Moreover, this study is the first example in the
      literature of an extensive evaluation of the correlative weights of the single
      components of the ZDOCK score on the thermodynamics and kinetics of binding of
      protein mutants compared to the native state.Finally, the results of this study
      corroborate and extend a previously developed quantitative model for in silico
      predictions of absolute protein-protein binding affinities spanning a wide range
      of values, i.e. from -10 up to -21 kcal/mol. The computational approach is simple
      and fast and can be used for structure-based design of protein-protein complexes
      and for in silico screening of mutational effects on protein-protein recognition.

PMID- 17559676
TI  - Improved benchmarks for computational motif discovery.
AB  - BACKGROUND: An important step in annotation of sequenced genomes is the
      identification of transcription factor binding sites. More than a hundred
      different computational methods have been proposed, and it is difficult to make
      an informed choice. Therefore, robust assessment of motif discovery methods
      becomes important, both for validation of existing tools and for identification
      of promising directions for future research. RESULTS: We use a machine learning
      perspective to analyze collections of transcription factors with known binding
      sites. Algorithms are presented for finding position weight matrices (PWMs),
      IUPAC-type motifs and mismatch motifs with optimal discrimination of binding
      sites from remaining sequence. We show that for many data sets in a recently
      proposed benchmark suite for motif discovery, none of the common motif models can
      accurately discriminate the binding sites from remaining sequence. This may
      obscure the distinction between the potential performance of the motif discovery
      tool itself versus the intrinsic complexity of the problem we are trying to
      solve. Synthetic data sets may avoid this problem, but we show on some previously
      proposed benchmarks that there may be a strong bias towards a presupposed motif
      model. We also propose a new approach to benchmark data set construction. This
      approach is based on collections of binding site fragments that are ranked
      according to the optimal level of discrimination achieved with our algorithms.
      This allows us to select subsets with specific properties. We present one
      benchmark suite with data sets that allow good discrimination between positive
      and negative instances with the common motif models. These data sets are suitable
      for evaluating algorithms for motif discovery that rely on these models. We
      present another benchmark suite where PWM, IUPAC and mismatch motif models are
      not able to discriminate reliably between positive and negative instances. This
      suite could be used for evaluating more powerful motif models. CONCLUSION: Our
      improved benchmark suites have been designed to differentiate between the
      performance of motif discovery algorithms and the power of motif models. We
      provide a web server where users can download our benchmark suites, submit
      predictions and visualize scores on the benchmarks.

PMID- 17559677
TI  - Expression of LIM kinase 1 is associated with reversible G1/S phase arrest,
      chromosomal instability and prostate cancer.
AB  - BACKGROUND: LIM kinase 1 (LIMK1), a LIM domain containing serine/threonine
      kinase, modulates actin dynamics through inactivation of the actin depolymerizing
      protein cofilin. Recent studies have indicated an important role of LIMK1 in
      growth and invasion of prostate and breast cancer cells; however, the molecular
      mechanism whereby LIMK1 induces tumor progression is unknown. In this study, we
      investigated the effects of ectopic expression of LIMK1 on cellular morphology,
      cell cycle progression and expression profile of LIMK1 in prostate tumors.
      RESULTS: Ectopic expression of LIMK1 in benign prostatic hyperplasia cells (BPH),
      which naturally express low levels of LIMK1, resulted in appearance of abnormal
      mitotic spindles, multiple centrosomes and smaller chromosomal masses.
      Furthermore, a transient G1/S phase arrest and delayed G2/M progression was
      observed in BPH cells expressing LIMK1. When treated with chemotherapeutic agent
      Taxol, no metaphase arrest was noted in these cells. We have also noted increased
      nuclear staining of LIMK1 in tumors with higher Gleason Scores and incidence of
      metastasis. CONCLUSION: Our results show that increased expression of LIMK1
      results in chromosomal abnormalities, aberrant cell cycle progression and
      alteration of normal cellular response to microtubule stabilizing agent Taxol;
      and that LIMK1 expression may be associated with cancerous phenotype of the
      prostate.

PMID- 17559678
TI  - Community views about routine HIV testing and antiretroviral treatment in
      Botswana: signs of progress from a cross sectional study.
AB  - BACKGROUND: The Botswana government began providing free antiretroviral therapy
      (ART) in 2002 and in 2004 introduced routine HIV testing (RHT) in government
      health facilities, aiming to increase HIV testing and uptake of ART. There have
      been concerns that the RHT programme might be coercive, lead to increased partner
      violence, and drive people away from government health services. METHODS: We
      conducted a household survey of 1536 people in a stratified random sample of
      communities across Botswana, asking about use and experience of government health
      services, views about RHT, views about ART, and testing for HIV in the last 12
      months. Focus groups further discussed issues about ART. RESULTS: Some 81% of
      respondents had visited a government clinic within the last 24 months. Of these
      92% were satisfied with the service, 96% felt they were treated with respect and
      90% were comfortable about confidentiality. Almost all respondents said they
      would choose a government clinic for treatment of AIDS. Nearly one half (47%)
      thought they were at risk of HIV. Those who had experienced partner violence
      within the last 12 months were more likely to think themselves at risk. One half
      of those who had visited a government facility in the last 24 months were offered
      HIV tests, and nearly half were tested. A few (8%) of those who were not asked
      thought they were tested. Most people (79%) had heard of RHT and 94% were in
      favour of it. Over one half (55%) of the entire sample had been tested for HIV
      within the last 12 months, one half of these through RHT. Women were more likely
      to have been tested. Nearly everyone (94%) had heard of ART and thought it could
      help AIDS. Focus groups identified problems of access to ART due to distance from
      treatment centres and long queues in the centres. CONCLUSION: Public awareness
      and approval of RHT was very high. The high rate of RHT has contributed to the
      overall high rate of HIV testing. The government's programme to increase HIV
      testing and uptake of ART is apparently working well. However, turning the tide
      of the epidemic will also require further concerted efforts to reduce the rate of
      new HIV infections.

PMID- 17559680
TI  - Novel rat Alzheimer's disease models based on AAV-mediated gene transfer to
      selectively increase hippocampal Abeta levels.
AB  - BACKGROUND: Alzheimer's disease (AD) is characterized by a decline in cognitive
      function and accumulation of amyloid-beta peptide (Abeta) in extracellular
      plaques. Mutations in amyloid precursor protein (APP) and presenilins alter APP
      metabolism resulting in accumulation of Abeta42, a peptide essential for the
      formation of amyloid deposits and proposed to initiate the cascade leading to AD.
      However, the role of Abeta40, the more prevalent Abeta peptide secreted by cells
      and a major component of cerebral Abeta deposits, is less clear. In this study,
      virally-mediated gene transfer was used to selectively increase hippocampal
      levels of human Abeta42 and Abeta40 in adult Wistar rats, allowing examination of
      the contribution of each to the cognitive deficits and pathology seen in AD.
      RESULTS: Adeno-associated viral (AAV) vectors encoding BRI-Abeta cDNAs were
      generated resulting in high-level hippocampal expression and secretion of the
      specific encoded Abeta peptide. As a comparison the effect of AAV-mediated
      overexpression of APPsw was also examined. Animals were tested for development of
      learning and memory deficits (open field, Morris water maze, passive avoidance,
      novel object recognition) three months after infusion of AAV. A range of
      impairments was found, with the most pronounced deficits observed in animals co
      injected with both AAV-BRI-Abeta40 and AAV-BRI-Abeta42. Brain tissue was analyzed
      by ELISA and immunohistochemistry to quantify levels of detergent soluble and
      insoluble Abeta peptides. BRI-Abeta42 and the combination of BRI-Abeta40+42
      overexpression resulted in elevated levels of detergent-insoluble Abeta. No
      significant increase in detergent-insoluble Abeta was seen in the rats expressing
      APPsw or BRI-Abeta40. No pathological features were noted in any rats, except the
      AAV-BRI-Abeta42 rats which showed focal, amorphous, Thioflavin-negative Abeta42
      deposits. CONCLUSION: The results show that AAV-mediated gene transfer is a
      valuable tool to model aspects of AD pathology in vivo, and demonstrate that
      whilst expression of Abeta42 alone is sufficient to initiate Abeta deposition,
      both Abeta40 and Abeta42 may contribute to cognitive deficits.

PMID- 17559681
TI  - A phase II trial of gemcitabine plus carboplatin in advanced transitional cell
      carcinoma of the urothelium.
AB  - BACKGROUND: Recent studies have demonstrated the effectiveness of cisplatin-based
      combinations in patients with advanced transitional cell carcinoma(TCC) of the
      urothelium. Concern over cisplatin toxicity instigated a search for alternative
      regimens. The aim of the study was to evaluate the activity and tolerability of
      gemcitabine plus carboplatin combination as first-line treatment in patients with
      advanced transitional cell carcinoma of the urothelium. METHODS: Patients with
      advanced TCC were treated with gemcitabine 1200 mg/m2 on days 1 and 8 and
      carboplatin area under the concentration-time curve(AUC) 5 on day 1 every 21
      days. RESULTS: Out of 41 patients, thirty-nine were evaluable for efficacy and 41
      for toxicity. A median of 5 cycles (range 1-6) was administered. Overall response
      rate was 46.2% (95% confidence interval: 32-65%) including 10.3% complete
      responses and 35.9% partial responses. The median time to progression and median
      overall survival were 7.5 months (95% confidence interval: 6.6-8.4 months) and
      13.6 months (95% confidence interval: 10.2-17.0 months), respectively. Grade 3/4
      neutropenia, anemia and thrombocytopenia were observed in 36.6%, 26.8, and 24.4%
      of patients, respectively. Non-hematological toxicity was generally mild. Grade 3
      vomiting occurred in 1 (2.4%) patients. CONCLUSION: The gemcitabine plus
      carboplatin combination is active in advanced TCC with acceptable toxicity and
      needs to be evaluated further and compared with other non-cisplatin-containing
      regimens. TRIAL REGISTRATION: ISRCTN88259320.

PMID- 17559679
TI  - Generation and analysis of ESTs from the eastern oyster, Crassostrea virginica
      Gmelin and identification of microsatellite and SNP markers.
AB  - BACKGROUND: The eastern oyster, Crassostrea virginica (Gmelin 1791), is an
      economically important species cultured in many areas in North America. It is
      also ecologically important because of the impact of its filter feeding behaviour
      on water quality. Populations of C. virginica have been threatened by
      overfishing, habitat degradation, and diseases. Through genome research,
      strategies are being developed to reverse its population decline. However, large
      scale expressed sequence tag (EST) resources have been lacking for this species.
      Efficient generation of EST resources from this species has been hindered by a
      high redundancy of transcripts. The objectives of this study were to construct a
      normalized cDNA library for efficient EST analysis, to generate thousands of
      ESTs, and to analyze the ESTs for microsatellites and potential single nucleotide
      polymorphisms (SNPs). RESULTS: A normalized and subtracted C. virginica cDNA
      library was constructed from pooled RNA isolated from hemocytes, mantle, gill,
      gonad and digestive tract, muscle, and a whole juvenile oyster. A total of 6,528
      clones were sequenced from this library generating 5,542 high-quality EST
      sequences. Cluster analysis indicated the presence of 635 contigs and 4,053
      singletons, generating a total of 4,688 unique sequences. About 46% (2,174) of
      the unique ESTs had significant hits (E-value </= 1e-05) to the non-redundant
      protein database; 1,104 of which were annotated using Gene Ontology (GO) terms. A
      total of 35 microsatellites were identified from the ESTs, with 18 having
      sufficient flanking sequences for primer design. A total of 6,533 putative SNPs
      were also identified using all existing and the newly generated EST resources of
      the eastern oysters. CONCLUSION: A high quality normalized cDNA library was
      constructed. A total of 5,542 ESTs were generated representing 4,688 unique
      sequences. Putative microsatellite and SNP markers were identified. These genome
      resources provide the material basis for future microarray development, marker
      validation, and genetic linkage and QTL analysis.

PMID- 17559682
TI  - Modeling the effect of levothyroxine therapy on bone mass density in
      postmenopausal women: a different approach leads to new inference.
AB  - BACKGROUND: The diagnosis, treatment and prevention of osteoporosis is a national
      health emergency. Osteoporosis quietly progresses without symptoms until late
      stage complications occur. Older patients are more commonly at risk of fractures
      due to osteoporosis. The fracture risk increases when suppressive doses of
      levothyroxine are administered especially in postmenopausal women. The question
      is; "When should bone mass density be tested in postmenopausal women after the
      initiation of suppressive levothyroxine therapy?". Standard guidelines for the
      prevention of osteoporosis suggest that follow-up be done in 1 to 2 years. We
      were interested in predicting the level of bone mass density in postmenopausal
      women after the initiation of suppressive levothyroxine therapy with a novel
      approach. METHODS: The study used data from the literature on the influence of
      exogenous thyroid hormones on bone mass density. Four cubic polynomial equations
      were obtained by curve fitting for Ward's triangle, trochanter, spine and femoral
      neck. The behaviors of the models were investigated by statistical and
      mathematical analyses. RESULTS: There are four points of inflexion on the graphs
      of the first derivatives of the equations with respect to time at about 6, 5, 7
      and 5 months. In other words, there is a maximum speed of bone loss around the
      6th month after the start of suppressive L-thyroxine therapy in post-menopausal
      women. CONCLUSION: It seems reasonable to check bone mass density at the 6th
      month of therapy. More research is needed to explain the cause and to confirm the
      clinical application of this phenomenon for osteoporosis, but such an approach
      can be used as a guide to future experimentation. The investigation of change
      over time may lead to more sophisticated decision making in a wide variety of
      clinical problems.

PMID- 17559683
TI  - High potential of escalating HIV transmission in a low prevalence setting in
      rural Tanzania.
AB  - BACKGROUND: Previous surveillance among antenatal clinic (ANC) attendees within
      the remote rural Manyara and Singida regions in Tanzania identified an imminent
      but still, relatively low HIV epidemic. We conducted a population-based HIV study
      to identify risk factors and validate the representativeness of ANC-based
      estimates. METHODS: Using a two-stage cluster sampling approach, we enrolled and
      then interviewed and collected saliva samples from 1,698 adults aged 15-49 years
      between December 2003 and May 2004. We anonymously tested saliva samples for IgG
      antibodies against HIV using Bionor HIV-1&2 assays (R). Risk factors for HIV
      infection were analysed by multivariate logistic regression using the rural
      population of the two regions as a standard. RESULTS: The prevalence of HIV in
      the general population was 1.8% (95% CI: 1.1-2.4), closely matching the ANC-based
      estimate (2.0%, 95% CI: 1.3-3.0). The female to male prevalence ratio was 0.8
      (95% CI 0.4-1.7). HIV was associated with being a resident in a fishing
      community, and having recently moved into the area. Multiple sexual partners
      increased likelihood of HIV infection by 4.2 times (95% CI; 1.2-15.4) for men. In
      women, use of contraceptives other than condoms was associated with HIV infection
      (OR 6.5, 95% CI; 1.7-25.5), while most of the population (78%) have never used
      condoms. CONCLUSION: The HIV prevalence from the general population was
      comparable to that of pregnant women attending antenatal clinics. The revealed
      patterns of sexual risk behaviours, for example, close to 50% of men having
      multiple partners and 78% of the population have never used a condom; it is
      likely that HIV infection will rapidly escalate. Immediate and effective
      preventive efforts that consider the socio-cultural contexts are necessary to
      reduce the spread of the infection.

PMID- 17559684
TI  - PET/CT staging followed by Intensity-Modulated Radiotherapy (IMRT) improves
      treatment outcome of locally advanced pharyngeal carcinoma: a matched-pair
      comparison.
AB  - BACKGROUND: Impact of non-pharmacological innovations on cancer cure rates is
      difficult to assess. It remains unclear, whether outcome improves with 2- [18-F]
      fluoro-2-deoxyglucose-positron emission tomography and integrated computer
      tomography (PET/CT) and intensity-modulated radiotherapy (IMRT) for curative
      treatment of advanced pharyngeal carcinoma. PATIENTS AND METHODS: Forty five
      patients with stage IVA oro- or hypopharyngeal carcinoma were staged with an
      integrated PET/CT and treated with definitive chemoradiation with IMRT from 2002
      until 2005. To estimate the impact of PET/CT with IMRT on outcome, a case-control
      analysis on all patients with PET/CT and IMRT was done after matching with eighty
      six patients treated between 1991 and 2001 without PET/CT and 3D-conformal
      radiotherapy with respect to gender, age, stage, grade, and tumor location with a
      ratio of 1:2. Median follow-up was eighteen months (range, 6-49 months) for the
      PET/CT-IMRT group and twenty eight months (range, 1-168 months) for the controls.
      RESULTS: PET/CT and treatment with IMRT improved cure rates compared to patients
      without PET/CT and IMRT. Overall survival of patients with PET/CT and IMRT was
      97% and 91% at 1 and 2 years respectively, compared to 74% and 54% for patients
      without PET/CT or IMRT (p = 0.002). The event-free survival rate of PET/CT-IMRT
      group was 90% and 80% at 1 and 2 years respectively, compared to 72% and 56% in
      the control group (p = 0.005). CONCLUSION: PET/CT in combination with IMRT and
      chemotherapy for pharyngeal carcinoma improve oncological therapy of pharyngeal
      carcinomas. Long-term follow-up is needed to confirm these findings.

PMID- 17559685
TI  - Modeling of the aorta artery aneurysms and renal artery stenosis using
      cardiovascular electronic system.
AB  - BACKGROUND: The aortic aneurysm is a dilatation of the aortic wall which occurs
      in the saccular and fusiform types. The aortic aneurysms can rupture, if left
      untreated. The renal stenosis occurs when the flow of blood from the arteries
      leading to the kidneys is constricted by atherosclerotic plaque. This narrowing
      may lead to the renal failure. Previous works have shown that, modelling is a
      useful tool for understanding of cardiovascular system functioning and
      pathophysiology of the system. The present study is concerned with the modelling
      of aortic aneurysms and renal artery stenosis using the cardiovascular electronic
      system. METHODS: The geometrical models of the aortic aneurysms and renal artery
      stenosis, with different rates, were constructed based on the original anatomical
      data. The pressure drop of each section due to the aneurysms or stenosis was
      computed by means of computational fluid dynamics method. The compliance of each
      section with the aneurysms or stenosis is also calculated using the mathematical
      method. An electrical system representing the cardiovascular circulation was used
      to study the effects of these pressure drops and the compliance variations on
      this system. RESULTS: The results showed the decreasing of pressure along the
      aorta and renal arteries lengths, due to the aneurysms and stenosis, at the peak
      systole. The mathematical method demonstrated that compliances of the aorta
      sections and renal increased with the expansion rate of the aneurysms and
      stenosis. The results of the modelling, such as electrical pressure graphs,
      exhibited the features of the pathologies such as hypertension and were compared
      with the relevant experimental data. CONCLUSION: We conclude from the study that
      the aortic aneurysms as well as renal artery stenosis may be the most important
      determinant of the arteries rupture and failure. Furthermore, these pathologies
      play important rules in increase of the cardiovascular pulse pressure which leads
      to the hypertension.

PMID- 17559686
TI  - A case-control study of occupational magnetic field exposure and Alzheimer's
      disease: results from the California Alzheimer's Disease Diagnosis and Treatment
      Centers.
AB  - BACKGROUND: A few studies have investigated a possible relationship between
      Alzheimer's disease (AD) and occupations with extremely low frequency magnetic
      field (MF) exposure. The purpose of this study was to further evaluate this
      possible association in a large patient population with expert diagnoses.
      METHODS: Subjects came from the 8 of the 9 California Alzheimer's Disease
      Diagnostic and Treatment Centers not previously used in an earlier study. Cases
      had probable or definite AD; controls primarily had a dementia-related problem
      other than vascular dementia (VaD) and some were not demented upon expert
      examination. Occupations were classified as having low, medium or high MF
      exposure, based upon previous research, replicating the exposure methodology used
      in our previous published studies. RESULTS: Occupational information was
      available for 98.6% of the 1527 cases and 98.5% of the 404 controls with age-at
      initial examination known to be at least 65. Among cases, 2.1% and 5.4% had high
      and medium occupational MF exposure, respectively, while among controls the
      percentages were 0.8% and 3.0%. In univariate analyses, the odds ratio (OR) for
      subjects with medium or high MF exposures combined was 2.1 (p < 0.01), while for
      high exposure alone the OR was 2.9 (p < 0.08). Two models were used in
      multivariate analyses, with gender, stroke, and either age-at-onset or age-at
      initial examination as covariates. The ORs for MF exposure varied little between
      the two models: 2.2 (p < 0.02) and 1.9 (p < 0.03) for medium or high exposure;
      2.7 (p < 0.11) and 3.2 (p < 0.12) for high exposure. OR estimates for females
      were higher than for males, but not significantly higher. There were no material
      differences between the ORs resulting from univariate and multivariate analyses.
      CONCLUSION: Elevated occupational MF exposure was associated with an increased
      risk of AD. Based on previous published studies, the results likely pertain to
      the general population.

PMID- 17559687
TI  - Predictive factors of virological success to salvage regimens containing protease
      inhibitors in HIV-1 infected children.
AB  - BACKGROUND: The impact of HIV drug resistance mutations in salvage therapy has
      been widely investigated in adults. By contrast, data available of predictive
      value of resistance mutations in pediatric population is scarce. METHODS: A
      multicenter, retrospective, observational study was conducted in children who
      received rescue salvage antiretroviral therapy after virologic failure. CD4
      counts and viral load were determined at baseline and 6 months after rescue
      intervention. Genotypic HIV-1 resistance test and virtual phenotype were assessed
      at baseline. RESULTS: A total of 33 children met the inclusion criteria and were
      included in the analysis. The median viral load (VL) and median percentage of
      CD4+ at baseline was 4.0 HIV-RNA log copies/ml and 23.0% respectively. The median
      duration that children were taking the new rescue regimen was 24.3 weeks (23.8
      30.6). Overall, 47% of the 33 children achieved virological response at 24 weeks.
      When we compared the group of children who achieved virological response with
      those who did not, we found out that mean number of PI related mutations among
      the group of responders was 3.8 vs. 5.4 (p = 0.115). Moreover, the mean number of
      susceptible drugs according to virtual phenotype clinical cut-off for maximal
      virologic response was 1.7 vs. 0.8 and mean number of susceptible drugs according
      to virtual phenotype cut-off for minimal virlologic response was 2.7 vs. 1.3 (p <
      0.01 in all cases). Eighteen children were rescued with a regimen containing a
      boosted-PI and virological response was significantly higher in those subjects
      compared with the others (61.1% vs. 28.6%, p < 0.01). CONCLUSION: Salvage
      treatment containing ritonavir boosted-PIs in children with virological failure
      was very efficient. The use of new tools as virtual phenotype could help to
      improve virologic success in pediatric population.

PMID- 17559688
TI  - HLA class II DR and DQ genotypes and haplotypes associated with rheumatic fever
      among a clinically homogeneous patient population of Latvian children.
AB  - The HLA system is being paid more and more attention because it is very
      significant in polymorphous immunological reactions. Several studies have
      suggested that genetic susceptibility to rheumatic fever (RF) and rheumatic heart
      disease (RHD) is linked to HLA class II alleles. We hypothesized that HLA class
      II associations within RHD may be more consistent if analysed amongst patients
      with a relatively homogeneous clinical outcome. A total of 70 RF patients under
      the age of 18 years were surveyed and analysed in Latvia. HLA genotyping of DQA1,
      DQB1 and DRB1 was performed using PCR with amplification with sequence-specific
      primers. We also used results from a previous study of DQB1 and DRB1 genotyping.
      In the RF patients, HLA class II DQA1*0401 was found more frequently compared to
      DQA1*0102. In the RF homogeneous patient groups, DQA1*0402 has the highest odds
      ratio. This is also the case in the multivalvular lesion (MVL) group, together
      with DQA1*0501 and DQA1*0301. In the chorea minor patients, DQA1*0201 was often
      found. Significant HLA DQA1 protective genotypes were not detected, although DQA1
      genotypes *0103/*0201 and *0301/*0501 were found significantly and frequently. In
      the distribution of HLA DRB1/DQA1 genotypes, *07/*0201 and *01/*0501 were
      frequently detected; these also occurred significantly often in the MVL group.
      The genotype *07/*0201 was frequently found in Sydenhamn's chorea patients that
      had also acquired RHD, but DRB1*04/DQA1*0401 was often apparent in RF patients
      without RHD. In the distribution of HLA DQA1/DQB1 genotypes, both in RF patients
      and in the homogeneous patient groups, the least frequent were *0102/*0602-8. The
      genotype DQA1*0501 with the DQB1 risk allele *0301 was often found in the MVL
      group. The genotype *0301/*0401-2 was frequently found in the RF and Sydenhamn's
      chorea patient groups. The haplotype *07-*0201-*0302 was frequently found in RF
      and homogeneous patient groups, including the MVL group. In addition, haplotypes
      *04-*0401-*0301 and *04-*0301-*0401-2 were frequent amongst patients with
      Sydenhamn's chorea. The protective alleles DQA1*0102 and DQB1*0602-8 in the
      haplotype DRB1*15 were less frequently found in RF patients. The results of the
      present study support our hypothesis and indicate that certain HLA class II
      haplotypes are associated with risk for or protection against RHD and that these
      associations are more evident in patients in clinically homogeneous groups.

PMID- 17559689
TI  - Transcript-level annotation of Affymetrix probesets improves the interpretation
      of gene expression data.
AB  - BACKGROUND: The wide use of Affymetrix microarray in broadened fields of
      biological research has made the probeset annotation an important issue. Standard
      Affymetrix probeset annotation is at gene level, i.e. a probeset is precisely
      linked to a gene, and probeset intensity is interpreted as gene expression. The
      increased knowledge that one gene may have multiple transcript variants clearly
      brings up the necessity of updating this gene-level annotation to a refined
      transcript-level. RESULTS: Through performing rigorous alignments of the
      Affymetrix probe sequences against a comprehensive pool of currently available
      transcript sequences, and further linking the probesets to the International
      Protein Index, we generated transcript-level or protein-level annotation tables
      for two popular Affymetrix expression arrays, Mouse Genome 430A 2.0 Array and
      Human Genome U133A Array. Application of our new annotations in re-examining
      existing expression data sets shows increased expression consistency among
      synonymous probesets and strengthened expression correlation between interacting
      proteins. CONCLUSION: By refining the standard Affymetrix annotation of
      microarray probesets from the gene level to the transcript level and protein
      level, one can achieve a more reliable interpretation of their experimental data,
      which may lead to discovery of more profound regulatory mechanism.

PMID- 17559690
TI  - Phono-spectrographic analysis of heart murmur in children.
AB  - BACKGROUND: More than 90% of heart murmurs in children are innocent. Frequently
      the skills of the first examiner are not adequate to differentiate between
      innocent and pathological murmurs. Our goal was to evaluate the value of a simple
      and low-cost phonocardiographic recording and analysis system in determining the
      characteristic features of heart murmurs in children and in distinguishing
      innocent systolic murmurs from pathological. METHODS: The system consisting of an
      electronic stethoscope and a multimedia laptop computer was used for the
      recording, monitoring and analysis of auscultation findings. The recorded sounds
      were examined graphically and numerically using combined phono-spectrograms. The
      data consisted of heart sound recordings from 807 pediatric patients, including
      88 normal cases without any murmur, 447 innocent murmurs and 272 pathological
      murmurs. The phono-spectrographic features of heart murmurs were examined
      visually and numerically. From this database, 50 innocent vibratory murmurs, 25
      innocent ejection murmurs and 50 easily confusable, mildly pathological systolic
      murmurs were selected to test whether quantitative phono-spectrographic analysis
      could be used as an accurate screening tool for systolic heart murmurs in
      children. RESULTS: The phono-spectrograms of the most common innocent and
      pathological murmurs were presented as examples of the whole data set. Typically,
      innocent murmurs had lower frequencies (below 200 Hz) and a frequency spectrum
      with a more harmonic structure than pathological cases. Quantitative analysis
      revealed no significant differences in the duration of S1 and S2 or loudness of
      systolic murmurs between the pathological and physiological systolic murmurs.
      However, the pathological murmurs included both lower and higher frequencies than
      the physiological ones (p < 0.001 for both low and high frequency limits). If the
      systolic murmur contained intensive frequency components of over 200 Hz, or its
      length accounted for over 80 % of the whole systolic duration, it was considered
      pathological. Using these criteria, 90 % specificity and 91 % sensitivity in
      screening were achieved. CONCLUSION: Phono-spectrographic analysis improves the
      accuracy of primary heart murmur evaluation and educates inexperienced listener.
      Using simple quantitative criterias a level of pediatric cardiologist is easily
      achieved in screening heart murmurs in children.

PMID- 17559691
TI  - CTLA4 polymorphism and primary Sjogren's syndrome.

PMID- 17559692
TI  - Behaviour change and competitive exclusion can explain the diverging HIV-1 and
      HIV-2 prevalence trends in Guinea-Bissau.
AB  - The aim of this study was to determine whether a temporary rise in sexual risk
      behaviour during war in Guinea-Bissau could explain the observed trends in HIV-1
      and HIV-2 prevalence, and to explore the possible contribution of competitive
      elimination of HIV-2 by HIV-1. A simulation model of the heterosexual
      transmission of sexually transmitted infections was parameterized using
      demographic, behavioural and epidemiological data from rural Guinea-Bissau, and
      fitted to the observed HIV-1 and HIV-2 trends with and without a historic rise in
      risk behaviour. The observed trends could only be simulated by assuming a
      temporary rise in risk behaviour. Around 30% of the projected decline in HIV-2
      prevalence from a peak of 8.7% to 4.3% in 2010 was due to competitive elimination
      by HIV-1. Importantly for public health, HIV-1 prevalence was predicted to
      continue increasing and to become the dominant HIV type by 2010. Data collection
      is required to validate this prediction.

PMID- 17559693
TI  - An outbreak of psittacosis in a bird park in Japan.
AB  - An outbreak of psittacosis related to a bird park occurred in Matsue City,
      Shimane Prefecture, Japan, during winter 2001. Seventeen cases of psittacosis (12
      visitors, three staff, and two student interns) were confirmed. A cohort study
      was conducted among the park staff and students to determine the risk factors for
      the development of acute serologically confirmed psittacosis (SCP) infection.
      Being 'bird staff' had an increased risk of SCP infection (RR 3.96, 95% CI 1.48
      10.58). Entering the staff building, where ill birds were maintained without
      proper isolation, was also associated with an increased risk of SCP infection (RR
      3.61, 95% CI 1.03-12.6). Isolation of ill birds and quarantine measures were
      found to be insufficient. Dehumidifiers and a high-pressure water spray under a
      closed ventilation environment may have raised the concentration of Chlamydophila
      psittaci in the hothouses. Bird park staff and visitors should be educated about
      psittacosis.

PMID- 17559694
TI  - Brucella isolated in humans and animals in Latin America from 1968 to 2006.
AB  - We report a retrospective analysis of 1933 Brucella strains isolated from humans
      and animals in Latin American countries between 1968 and 1991 and in Argentina
      between 1994 and 2006. During the first period 50% of strains were from humans,
      mainly from Argentina, Mexico and Peru but, while B. suis was the main cause of
      infection in Argentina, B. melitensis was responsible for most infections in the
      other countries. In Argentina in the later years, B. melitensis and B. suis were
      observed more frequently than in the first period while isolation of B. abortus
      decreased. Of 145 B. melitensis human isolates, eight gave susceptibility
      patterns to dyes and penicillin and two were B. melitensis biovar 3, which has
      never been reported in animals. Forty-six percent of B. suis isolated were
      resistant to dyes which is an atypical feature in this species.

PMID- 17559695
TI  - Use of sentinel chickens to study the transmission dynamics of West Nile virus in
      a sahelian ecosystem.
AB  - During the 2003 rainy season, a follow-up survey in sentinel chickens was
      undertaken to assess the seasonal transmission of West Nile virus (WNV) in a
      sahelian ecosystem: the Ferlo (Senegal). The estimated incidence rate in chickens
      was 14% (95% CI 7-29), with a very low level of transmission between July and
      September, and a transmission peak occurring between September and October.
      Comparing these results with the estimate obtained from a previous transversal
      serological study performed on horses the same year in the same area, the
      relevance of sentinel chickens in estimating the WNV transmission rate is
      highlighted. Conventionally adult mosquito populations disappear during the dry
      season but WN disease was shown to be endemic in the study area. The mechanisms
      of virus maintenance are discussed.

PMID- 17559696
TI  - An outbreak of pig rabies in Hunan province, China.
AB  - The first dog-associated outbreak of rabies in swine in China (Hunan province)
      has been diagnosed and the related virus isolated. Sequence analysis showed that
      the pig isolate was a genotype 1 rabies virus with a very high nucleotide
      identity to local dog isolates.

PMID- 17559697
TI  - Olive oil containing olive oil fatty acid esters of plant sterols and dietary
      diacylglycerol reduces low-density lipoprotein cholesterol and decreases the
      tendency for peroxidation in hypercholesterolaemic subjects.
AB  - Plant sterols (PS) and MUFA are well-documented cholesterol lowering agents. We
      aimed to determine the effect of PS esterified to olive oil fatty acids (PS-OO)
      on blood lipid profile and lipid peroxidation in hypercholesterolaemic subjects.
      Twenty-one moderately overweight, hypercholesterolaemic subjects consumed three
      consecutive treatment diets, each lasting 28 d and separated by 4-week washout
      periods, using a randomized crossover design. Diets contained 30 % energy as fat,
      70 % of which was provided by olive oil (OO), and differed only in the treatment
      oils: OO, PS esterified to sunflower oil fatty acids (PS-SO), and PS-OO. Both PS
      SO and PS-OO treatments provided 1.7 g PS /d. PS-OO and PS-SO consumption
      resulted in a decrease (P = 0.0483) in LDL-cholesterol (LDL-C) concentrations
      compared with the OO diet. Although total cholesterol and apo B-100 levels were
      not significantly affected, PS-SO and, to some extent, PS-OO reduced the
      total:HDL-cholesterol (HDL-C) ratio (P = 0.0142) and the apo B-100:apo A-I ratio
      (P = 0.0168) compared with the OO diet. There were no differences across diets in
      lipoprotein(a) (Lp(a)) and lipid peroxidation levels. However, following
      consumption of OO and PS-SO, Lp(a) concentrations increased (P = 0.0050 and
      0.0421, respectively), while PS-OO treatment did not affect Lp(a) levels.
      Furthermore, there was a decrease (P = 0.0097) in lipid peroxidation levels with
      PS-OO treatment during the supplementation phase. Our results suggest that
      supplementing an OO-rich diet with PS-OO favourably alters the plasma lipid
      profile and may decrease the susceptibility of LDL-C to lipid peroxidation in
      hypercholesterolaemic subjects.

PMID- 17559698
TI  - Strawberry pelargonidin glycosides are excreted in urine as intact glycosides and
      glucuronidated pelargonidin derivatives in rats.
AB  - Anthocyanins are natural dietary pigments with a wide array of biological
      properties that are possibly involved in the prevention of various diseases.
      These properties depend on their absorption and metabolism in the body. In the
      present study we first examined the gastric and intestinal absorption of
      pelargonidin 3-glucoside (Pg 3-glc) using rat in situ models. A high proportion
      of Pg 3-glc was rapidly absorbed from both the stomach (23 %) and small intestine
      (24 %). Its metabolism was further studied by feeding rats during 8 d with a diet
      enriched in freeze-dried strawberries. Only low amounts of total anthocyanins
      were recovered in 24 h urine (0.163 (SEM 0.013) % of ingested anthocyanins; n 8).
      Strawberry anthocyanins were analysed in urine by HPLC-electrospray ionisation
      tandem MS. Similar proportions of intact glycosides (about 53 %) and
      glucuronidated metabolites (about 47 %) were found. Pg 3-glc was thus
      glucuronidated to a larger extent than cyanidin 3-glucoside. These results
      highlight the influence of the aglycone structure on anthocyanin metabolism.

PMID- 17559699
TI  - Effect of dietary conjugated linoleic acid on body composition and energy balance
      in broiler chickens.
AB  - The effect of dietary conjugated linoleic acid (CLA) on body composition and
      energy metabolism was investigated in broiler chickens. Male broiler chicks were
      assigned to receive either a control diet (1 % sunflower oil) or a diet
      containing CLA (1 % of a 1:1 mixture of trans-10, cis-12 and cis-9, trans-11
      isomers of octadecadienoic acid). The diets were fed ad libitum for 3 weeks and
      there were eight replicates per diet, each replicate including four chickens so
      that each treatment had thirty-two animals. The proportion of body fat was lower
      in the control group than in the CLA group. No significant differences as to the
      proportions of body water, ash and protein were observed. Feed and energy intake
      were significantly lower in CLA-fed birds. The percentage of ingested energy lost
      in excreta was higher after CLA feeding and heat expenditure as a percentage of
      ingested energy was lower in the CLA-fed group. The CLA-fed group showed a higher
      percentage of SFA and lower percentages of MUFA and PUFA in carcass fat. It is
      concluded that CLA stimulated de novo fatty acid synthesis and lowered desaturase
      activity.

PMID- 17559700
TI  - Hepatic structural alteration in adult programmed offspring (severe maternal
      protein restriction) is aggravated by post-weaning high-fat diet.
AB  - The present study aimed to evaluate the effects of a post-weaning high-fat (HF)
      diet upon hepatic morphology in rats subjected to perinatal protein restriction.
      Pregnant Wistar rats were assigned to a normal-protein diet (NP; with 19 % of
      protein) or a low-protein (LP) diet (with 5 % of protein). At weaning, the
      following groups were formed: NP and NP-HF, males and females, which were fed
      standard chow and an HF diet, respectively. Likewise, LP rat dams originated LP
      and LP-HF offspring, both sexes. Euthanasia was performed at 6 months of age.
      Three-way ANOVA disclosed a three-factor interaction among sex, perinatal diet
      and HF diet in relation to body mass, retroperitoneal fat pad, liver mass:tibia
      length ratio, binucleation rate and hepatocyte area at 6 months old (P < 0.05).
      The high-fat diet intensified the effects of perinatal protein restriction
      concerning systolic blood pressure, genital fat pad and hepatocyte number (P <
      0.05; two-way ANOVA). Furthermore, higher steatosis rates and insulin and leptin
      concentrations were found in males fed on the HF diet, indicating a sex-post
      weaning diet interaction (P < 0.05; two-way ANOVA). Fetal programming and HF diet
      as a single stimulus caused mild hypertension at 3 months, an important reduction
      in hepatocyte number as well as stage 1 steatosis at 6 months. However,
      hypertension and hepatocyte number deficit were worsened and grade 2 steatosis
      occurred after exposure to the HF diet. All of these serve to highlight the
      paramount importance of intra-uterine conditions and postnatal diet quality when
      it comes to the pathogenesis of chronic diseases.

PMID- 17559701
TI  - Effects of anthocyanin-rich purple potato flakes on antioxidant status in F344
      rats fed a cholesterol-rich diet.
AB  - We examined the antioxidant effects of polyphenol/anthocyanin-rich potato
      (Solanum tuberosum cv. Shadow-Queen) flakes in male rats fed a high-cholesterol
      diet. The rats were served either a high-cholesterol (0.5% cholesterol plus
      0.125% sodium cholate) diet, or a high-cholesterol diet containing a mixture of
      243 g alpha-maize starch/kg supplemented with one of the following (per kg diet):
      300 g medium purple potato (Shadow-Queen), 300 g white potato (Solanum tuberosum
      cv. Toyoshiro) or 300 g dark purple sweet potato (Ipomoea batatas cv.
      Ayamurasaki) flakes for 28 d. We analysed thiobarbituric acid reactive substance
      (TBARS) levels in the serum and liver, and antioxidant enzyme activities in the
      liver. At this dosage, TBARS levels in the serum and liver of the Shadow-Queen
      and Ayamurasaki groups were significantly lower than those in the control and
      Toyoshiro groups. The serum urate levels in all the flake groups were
      significantly lower than that in the control group. The hepatic glutathione
      levels in the Shadow-Queen and Ayamurasaki groups were significantly higher than
      in the control and Toyoshiro groups. The activities of hepatic glutathione
      reductase and glutathione S-transferase in the Shadow-Queen and Ayamurasaki
      groups were significantly greater than those in the control group. These results
      show that modulation of antioxidant enzymes and oxidative status in the serum and
      liver by the purple potato flake diet (Shadow-Queen) containing
      polyphenols/anthocyanins may play an important role in the protection against
      adverse effects related to oxidative damage in rats fed a high-cholesterol diet.

PMID- 17559703
TI  - Biased emotional attention in post-traumatic stress disorder: a help as well as a
      hindrance?
AB  - BACKGROUND: From a cognitive neuroscience perspective, the emotional attentional
      bias in post-traumatic stress disorder (PTSD) could be conceptualized either as
      emotional hyper-responsiveness or as reduced priming of task-relevant
      representations due to dysfunction in 'top-down' regulatory systems. We
      investigated these possibilities both with respect to threatening and positive
      stimuli among traumatized individuals with and without PTSD. METHOD: Twenty-two
      patients with PTSD, 21 trauma controls and 20 non-traumatized healthy
      participants were evaluated on two tasks. For one of these tasks, the affective
      Stroop task (aST), the emotional stimuli act as distracters and interfere with
      task performance. For the other, the emotional lexical decision task (eLDT),
      emotional information facilitates task performance. RESULTS: Compared to trauma
      controls and healthy participants, patients with PTSD showed increased
      interference for negative but not positive distracters on the aST and increased
      emotional facilitation for negative words on the eLDT. CONCLUSIONS: These
      findings document that hyper-responsiveness to threat but not to positive stimuli
      is specific for patients with PTSD.

PMID- 17559704
TI  - A nationwide US study of post-traumatic stress after hospitalization for physical
      injury.
AB  - BACKGROUND: Injured survivors of individual and mass trauma are at risk for
      developing post-traumatic stress disorder (PTSD). Few investigations have
      assessed PTSD after injury in large samples across diverse acute care hospital
      settings. METHOD: A total of 2931 injured trauma survivors aged 18-84 who were
      representative of 9983 in-patients were recruited from 69 hospitals across the
      USA. In-patient medical records were abstracted, and hospitalized patients were
      interviewed at 3 and 12 months after injury. Symptoms consistent with a DSM-IV
      diagnosis of PTSD were assessed with the PTSD Checklist (PCL) 12 months after
      injury. RESULTS: Approximately 23% of injury survivors had symptoms consistent
      with a diagnosis of PTSD 12 months after their hospitalization. Greater levels of
      early post-injury emotional distress and physical pain were associated with an
      increased risk of symptoms consistent with a PTSD diagnosis. Pre-injury,
      intensive care unit (ICU) admission [relative risk (RR) 1.17, 95% confidence
      interval (CI) 1.02-1.34], pre-injury depression (RR 1.33, 95% CI 1.15-1.54),
      benzodiazepine prescription (RR 1.46, 95% CI 1.17-1.84) and intentional injury
      (RR 1.32, 95% CI 1.04-1.67) were independently associated with an increased risk
      of symptoms consistent with a PTSD diagnosis. White injury survivors without
      insurance demonstrated approximately twice the rate of symptoms consistent with a
      diagnosis of PTSD when compared to white individuals with private insurance. By
      contrast, for Hispanic injury survivors PTSD rates were approximately equal
      between uninsured and privately insured individuals. CONCLUSIONS: Nationwide in
      the USA, more than 20% of injured trauma survivors have symptoms consistent with
      a diagnosis of PTSD 12 months after acute care in-patient hospitalization.
      Coordinated investigative and policy efforts could target mandates for high
      quality PTSD screening and intervention in acute care medical settings.

PMID- 17559705
TI  - Attitudes to depression and its treatment in primary care.
AB  - BACKGROUND: Undertreatment of depression in primary care is common. Efforts to
      address this tend to overlook the role of patient attitudes. Our aim was to
      validate and describe responses to a questionnaire about attitudes to depression
      and its treatment in a sample with experience of moderate and severe depressive
      episodes. METHOD: Cross-sectional survey of 866 individuals with a confirmed
      history of an ICD-10 depressive episode in the 12 months preceding interview,
      recruited from 7271 consecutive general practitioner (GP) attendees in 36 general
      practices in England and Wales. Attitudes to and beliefs about depression were
      assessed using a 19-item self-report questionnaire. RESULTS: Factor analysis
      resulted in a three-factor solution: factor 1, depression as a disabling,
      permanent state; factor 2, depression as a medical condition responsive to
      support; and factor 3, antidepressants are addictive and ineffective.
      Participants who received and adhered to antidepressant medication and disclosed
      their depression to family and friends had significantly lower scores on factors
      1 and 3 but higher scores on factor 2. CONCLUSIONS: People with moderate or
      severe depressive episodes have subtle and divergent views about this condition,
      its outcome, and appropriate help. Such beliefs should be considered in primary
      care as they may significantly impact on help seeking and adherence to treatment.

PMID- 17559706
TI  - Nursing care for people with frontal-lobe dementia - difficulties and
      possibilities.
AB  - BACKGROUND: Nursing care for people with dementia diseases affecting the frontal
      lobes places special demands on staff, but there is little information available
      about how best to tailor nursing care. The aim of this study was to describe
      nurses' experience of difficulties and possibilities in caring for people with
      dementia diseases with frontal-lobe dysfunction. METHOD: The study was carried
      out as a descriptive qualitative study. Data collected during interviews with
      nursing staff (n = 10) were analyzed using qualitative content analysis. RESULTS:
      The difficulties experienced were related to the patients' lack of inhibition and
      judgment, anxiety, agitation, reduced ability to deal with physical needs,
      egocentricity, imbalance between rest and activity and depressed mood. The
      possibilities were seen in relation to the nursing staff's professional
      encounters, characterized as being clear and consistent, a step ahead, flexible,
      calm and creating a positive atmosphere, close and trusting and being and doing
      things together. Continuous feedback and support were prerequisites for the
      engagement of the staff. CONCLUSION: Nursing care in this context involves
      ethical issues whereby the residents' integrity must be balanced against a safe
      and secure environment. Nursing care is a sensitive but also demanding task,
      where nurses' actions can reduce the negative effects of the disease. It is
      therefore important to support staff in nursing care so they are able to manage
      their work and reduce the risk of emotional exhaustion.

PMID- 17559707
TI  - The reliability and validity of the Norwegian version of the Neuropsychiatric
      Inventory, nursing home version (NPI-NH).
AB  - BACKGROUND: Psychiatric symptoms and behavioral disturbances are highly prevalent
      in the residents of nursing homes. The Neuropsychiatric Inventory (NPI) is a
      commonly used scale for the assessment of such symptoms in diverse settings. We
      have conducted a study of the reliability and the validity of the Norwegian
      version of the NPI nursing home version (NPI-NH). METHODS: The reliability study
      comprised 41 patients. We established inter-rater reliability between raters with
      various levels of health education using kappa statistics. Fifty patients were
      included in the validity study. The patients were examined by a physician, who
      also rated the patient's behavior using "behavioral pathology in Alzheimer's
      disease" (BEHAVE-AD). Subsequently, a research nurse performed a standardized
      interview using the NPI and the Cornell scale. Concurrent validity of the NPI and
      the BEHAVE-AD was analyzed. RESULTS: Internal consistency, as measured by
      Cronbach's alpha was above 0.8. Inter-rater reliability was, except for one item,
      between 0.85 and 1.0 across assessors with different levels of health education.
      All correlations between the NPI and the BEHAVE-AD were significant, ranging from
      0.38 to 0.72. The weakest correlations were between items assessing affective and
      anxiety symptoms. CONCLUSION: The Norwegian version of the NPI-NH is a reliable
      and valid instrument for assessing psychiatric symptoms and behavioral
      disturbances in the residents of nursing homes. The investigation of depressive
      symptoms merits particular attention.

PMID- 17559708
TI  - High prevalence of dementia among older adults from poor socioeconomic
      backgrounds in Sao Paulo, Brazil.
AB  - BACKGROUND: The aim of this study was to determine the prevalence of dementia in
      a socioeconomically disadvantaged population of older adults living in the city
      of Sao Paulo, Brazil. METHODS: A cross-sectional one-phase population-based study
      was carried out among all residents aged > or = 65 in defined census sectors of
      an economically disadvantaged area of Sao Paulo. Identification of cases of
      dementia followed the protocol developed by the 10/66 Dementia Research Group.
      RESULTS: Of 2072 individuals in the study, 105 met the criteria for a diagnosis
      of dementia, yielding a prevalence of 5.1%. Prevalence increased with age for
      both men and women after age 75 years, but was stable from 65 to 74 years. Low
      education and income were associated with increased risk of dementia.
      CONCLUSIONS: The prevalence of dementia among older adults from low socioeconomic
      backgrounds is high. This may be partly due to adverse socioeconomic conditions
      and consequent failure to compress morbidity into the latter stages of life. The
      increasing survival of poorer older adults with dementia living in developing
      countries may lead to a rapid increase in the prevalence of dementia worldwide.

PMID- 17559709
TI  - Brain-derived neurotrophic factor-deficient mice exhibit a hippocampal
      hyperserotonergic phenotype.
AB  - Growing evidence supports the involvement of brain-derived neurotrophic factor
      (BDNF) in mood disorders and the mechanism of action of antidepressant drugs.
      However, the relationship between BDNF and serotonergic signalling is poorly
      understood. Heterozygous mutants BDNF +/- mice were utilized to investigate the
      influence of BDNF on the serotonin (5-HT) system and the activity of the
      serotonin transporter (SERT) in the hippocampus. The zero net flux method of
      quantitative microdialysis revealed that BDNF +/- heterozygous mice have
      increased basal extracellular 5-HT levels in the hippocampus and decreased 5-HT
      reuptake capacity. In keeping with these results, the selective serotonin
      reuptake inhibitor paroxetine failed to increase hippocampal extracellular 5-HT
      levels in BDNF +/- mice while it produced robust effects in wild-type
      littermates. Using in-vitro autoradiography and synaptosome techniques, we
      investigated the causes of attenuated 5-HT reuptake in BDNF +/- mice. A
      significant decrease in [3H]citalopram-binding-site density in the CA3 subregion
      of the ventral hippocampus and a significant reduction in [3H]5-HT uptake in
      hippocampal synaptosomes, revealed mainly a decrease in SERT function. However, 5
      HT1A autoreceptors were not desensitized in BDNF +/- mice. These results provide
      evidence that constitutive reductions in BDNF modulate SERT function reuptake in
      the hippocampus.

PMID- 17559710
TI  - A randomized, double-blind clinical trial on the efficacy of cortical direct
      current stimulation for the treatment of major depression.
AB  - Preliminary findings suggest that transcranial direct current stimulation (tDCS)
      can have antidepressant effects. We sought to test this further in a parallel
      group, double-blind clinical trial with 40 patients with major depression,
      medication-free randomized into three groups of treatment: anodal tDCS of the
      left dorsolateral prefrontal cortex (active group - 'DLPFC'); anodal tDCS of the
      occipital cortex (active control group - 'occipital') and sham tDCS (placebo
      control group - 'sham'). tDCS was applied for 10 sessions during a 2-wk period.
      Mood was evaluated by a blinded rater using the Hamilton Depression Rating Scale
      (HDRS) and Beck Depression Inventory (BDI). The treatment was well tolerated with
      minimal side-effects that were distributed equally across all treatment groups.
      We found significantly larger reductions in depression scores after DLPFC tDCS
      [HDRS reduction of 40.4% (+/-25.8%)] compared to occipital [HDRS reduction of
      21.3% (+/-12.9%)] and sham tDCS [HDRS reduction of 10.4% (+/-36.6%)]. The
      beneficial effects of tDCS in the DLPFC group persisted for 1 month after the end
      of treatment. Our findings support further investigation on the effects of this
      novel potential therapeutic approach - tDCS - for the treatment of major
      depression.

PMID- 17559711
TI  - Evidence for sex ratio distortion by a new microsporidian parasite of a Corophiid
      amphipod.
AB  - In this paper, we describe the occurrence of a microsporidian parasite in female
      biased populations of an intertidal amphipod, Corophium volutator (Pallas), at
      mudflat sites in the Bay of Fundy, Canada. Sequence data for the parasite's 16S
      rDNA indicate that it is a novel microsporidian species. This parasite was found
      principally in female host gonads, indicating that it might be a vertically
      transmitted, sex-distorting microparasite. At 4 sites each sampled in early and
      mid-summer, parasite prevalence varied from 0 to 21%. In the lab, infected
      mothers gave rise to more female-biased broods, than did uninfected mothers.
      Infection was not associated with size of females or with lowered survivorship of
      their young. Surprisingly, infected mothers actually had higher fertility
      controlling for body length than did uninfected mothers. Taken together, our
      results suggest that this novel microsporidian is likely a feminizing
      microparasite and is a contributing factor to local and widespread sex ratio
      distortion in C. volutator.

PMID- 17559712
TI  - Metastatic squamous cell carcinoma of occult primary: beware the tonsillar
      remnant.
AB  - INTRODUCTION: Metastasis of squamous cell carcinoma to the neck with an occult
      primary is a recognised clinical and pathological entity. Despite well
      established diagnostic protocols, this condition still represents a management
      challenge. CASE REPORT: We report the case of a 46-year-old man who presented
      with metastatic cervical lymphadenopathy of unknown origin. He had undergone
      tonsillectomy as a child. The only abnormal finding was the presence of a
      tonsillar remnant, which harboured the primary carcinoma. CONCLUSION: According
      to our literature search, this is the only recorded case in which the index
      tumour was found in a tonsillar remnant. This case illustrates the importance of
      thorough clinical examination in patients with potential unknown primaries, and
      of the need, in previously tonsillectomised patients, to perform excisional
      biopsy of the tonsillar remnant.

PMID- 17559713
TI  - Paediatric neck abscesses: microbiology and management.
AB  - INTRODUCTION: Paediatric neck abscesses remain common problems which are
      sometimes difficult to manage. METHODS AND MATERIALS: We conducted a
      retrospective study of 64 children who underwent incision and drainage of neck
      abscesses at Leeds General Infirmary from 1 February 2002 to 31 July 2006. The
      aim of this study was to identify the presenting symptoms in children, the
      appropriateness of prescribed antibiotics and the role of atypical mycobacteria
      in neck infections. The outcome measure was clinical resolution of the abscess.
      RESULTS: The mean presenting age was 44.2 months (3.68 years). The commonest sign
      and symptom was neck mass (96.9 per cent). The mean period of hospitalisation was
      3.7 (+/- standard deviation of 1.9) days. Staphylococcus aureus (48.4 per cent)
      was the commonest organism cultured. Atypical mycobacteria were found in only 4.7
      per cent of the specimens. Flucloxacillin was the most common antibiotic used
      (57.8 per cent), often in combination with other antimicrobials. The abscess
      recurrence rate was 4.7 per cent. No fatalities occurred in this series of
      patients. CONCLUSION: Appropriately prescribed intravenous antibiotics and
      surgical drainage remain the central core of treatment. Atypical mycobacterial
      infection is an important differential diagnosis of a painless, cervico-facial
      mass. An algorithm for the management of paediatric neck abscesses is proposed.

PMID- 17559714
TI  - History of myringotomy and grommets.
AB  - The first recorded myringotomy was in 1649. Astley Cooper presented two papers to
      the Royal Society in 1801, based on his observation that myringotomy could
      improve hearing. Widespread inappropriate use of the procedure followed, with no
      benefit to patients; this led to it falling from favour for many decades. Hermann
      Schwartze reintroduced myringotomy later in the nineteenth century. It had been
      realised earlier that the tympanic membrane heals spontaneously, and much
      experimentation took place in attempting to keep the perforation open. The first
      described grommet was made of gold foil. Other materials were tried, including
      Politzer's attempts with rubber. Armstrong's vinyl tube effectively reintroduced
      grommets into current practice last century. There have been many eponymous
      variants, but the underlying principle of creating a perforation and maintaining
      it with a ventilation tube has remained unchanged. Recent studies have cast doubt
      over the long-term benefits of grommet insertion; is this the end of the third
      era?

PMID- 17559715
TI  - Hepatic necrosis following repair of totally anomalous pulmonary venous
      connection.
AB  - We report a case of an infant with asplenia syndrome, isomerism of the right
      atrial appendages, and totally anomalous pulmonary venous connection who
      experienced hepatic failure following surgical correction of the anomalous
      pulmonary venous connection. We describe associated anomalies of the portal
      venous system.

PMID- 17559716
TI  - Intuition: a fundamental bridging construct in the behavioural sciences.
AB  - The concept of intuition has, until recently, received scant scholarly attention
      within and beyond the psychological sciences, despite its potential to unify a
      number of lines of inquiry. Presently, the literature on intuition is
      conceptually underdeveloped and dispersed across a range of domains of
      application, from education, to management, to health. In this article, we
      clarify and distinguish intuition from related constructs, such as insight, and
      review a number of theoretical models that attempt to unify cognition and affect.
      Intuition's place within a broader conceptual framework that distinguishes
      between two fundamental types of human information processing is explored. We
      examine recent evidence from the field of social cognitive neuroscience that
      identifies the potential neural correlates of these separate systems and conclude
      by identifying a number of theoretical and methodological challenges associated
      with the valid and reliable assessment of intuition as a basis for future
      research in this burgeoning field of inquiry.

PMID- 17559717
TI  - The role of rumination, attentional biases and stress in psychological distress.
AB  - This experimental study examines the relationship between rumination and
      attentional bias. Additionally, the study aims to determine, within a diathesis
      stress framework, whether rumination or attentional bias (or both) can
      prospectively predict psychological distress. Eighty-one participants completed
      selected measures of rumination and psychological distress at time one, in
      addition to experimental manipulations of rumination and mood, and measures of
      mood and attentional bias at time two. Seventy-three participants (90% follow-up)
      completed final measures of stress and psychological distress approximately 3
      weeks later. In combination with negative mood, inducing rumination decreased
      positive attentional bias, whilst inducing distraction increased positive
      attentional bias. Rumination and stress interacted to predict change in
      psychological distress. Negative attentional bias showed a trend towards
      interacting with rumination and stress to predict dysphoria. The findings
      supported the proposed diathesis-stress models. In addition, a causal
      relationship between rumination and positive attentional bias has been
      empirically established for the first time.

PMID- 17559719
TI  - Combination therapy for the treatment of multiple sclerosis: challenges and
      opportunities.
AB  - OBJECTIVE: Multiple sclerosis (MS) is a complex, heterogeneous disease. Standard
      treatment of relapsing MS includes interferon beta (IFNbeta) and glatiramer
      acetate. These agents reduce relapse rates, and IFNbeta-1a is associated with a
      slowing of disease progression. Despite treatment, many patients experience
      disease progression, prompting neurologists to use combination therapies to delay
      this progression. Agents that may be considered for combination therapy are those
      with unique mechanisms of action that exert additive or synergistic efficacy.
      This article reviews combination treatment with immunosuppressive therapies and
      new agents for the management of MS. METHODS: The Medline and EMBASE databases
      were searched for clinical trials using the following search terms: multiple
      sclerosis, interferon, Avonex, Betaseron, Rebif, glatiramer, copolymer 1,
      Copaxone, immunosuppressant, cytotoxic, corticosteroid, azathioprine,
      cyclophosphamide, methotrexate, mitoxantrone, natalizumab, combination therapy.
      The National MS Society website was searched for clinical trials of combination
      therapies. RESULTS: Several small studies have analyzed the effects of
      immunosuppressive therapy added to IFNbeta treatment, and some encouraging
      results have been obtained. Few data are available on combination therapy with
      new drug classes; however, current data suggest that combination therapy with new
      agents is effective. Although the available data on combination regimens are
      promising, interpretation is limited by lack of controlled study design, small
      patient population, and short study duration. CONCLUSIONS: Combination of
      standard therapies with immunosuppressive agents or with new therapies may
      provide synergistic effects that will likely benefit patients with MS. Larger,
      well-controlled trials need to be conducted.

PMID- 17559720
TI  - The development of new-onset type 2 diabetes associated with choosing a calcium
      channel blocker compared to a diuretic or beta-blocker.
AB  - OBJECTIVE: It has been acknowledged that patients who receive a beta-blocker or
      diuretic based regimen are at increased risk of developing new-onset diabetes.
      Recently, angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin
      receptor blockers (ARBs) have been shown to decrease patients' odds of developing
      new-onset type 2 diabetes. A number of large placebo-controlled multi-center
      trials in post-myocardial infarction and heart failure patients have shown the
      ability of renin-angiotensin-aldosterone system medications to reduce the onset
      of type 2 diabetes. Pharmacologic data has shown improved insulin sensitivity
      with ACEIs and ARBs. Controversy persists regarding the influence of calcium
      channel blockers on the development of new-onset diabetes. RESEARCH DESIGN AND
      METHODS: Two reviewers conducted a systematic literature search of Medline,
      EMBASE, CINAHL, and the Cochrane Library (1966 to December 2006) to extract a
      consensus of trial data involving calcium channel blockers versus diuretics or
      beta-blockers with an endpoint of new-onset type 2 diabetes. Studies were
      included if they were randomized controlled trials versus routine treatment, not
      observational studies of clinical practice. A random-effects model was utilized.
      Subgroup and sensitivity analyses were conducted. RESULTS: Out of 1721 trials,
      six meeting inclusion criteria were identified, including 99 006 patients.
      Calcium channel blockers were associated with a reduced incidence of new-onset
      type 2 diabetes (odds ratio 0.81; 95% confidence interval [CI] 0.73-0.90; p =
      0.0001) compared with diuretic or beta-blocker therapy. The reduction in new
      onset type 2 diabetes was maintained when a calcium channel blocker was compared
      to only thiazide diuretics (OR 0.86; 95% CI 0.75-0.99; p = 0.0346). The meta
      analysis was limited by the varying definition of new-onset type 2 diabetes
      mellitus, as well as the potential for publication bias, which is a limit of any
      meta-analysis. CONCLUSIONS: Calcium channel blockers may be associated with
      reduced odds of developing new-onset type 2 diabetes compared to diuretics and
      beta-blockers.

PMID- 17559721
TI  - The emerging role of platelet glycoprotein IIb/IIIa inhibitors in managing high
      risk patients with non-ST segment elevation acute coronary syndromes.
AB  - BACKGROUND: Current practice guidelines recommend administering a platelet
      glycoprotein IIb/IIIa inhibitor, in conjunction with aspirin and heparin, for
      patients with non-ST segment elevation (NSTE) acute coronary syndromes (ACS) for
      whom an early invasive management strategy is planned. However, optimal timing of
      glycoprotein IIb/IIIa inhibitor administration - 'upstream' in the coronary care
      unit or 'downstream' when the patient goes to the catheterization laboratory -
      has not been established. SCOPE: This paper evaluates recent trial results that
      help to better define the role of platelet glycoprotein IIb/IIIa inhibitors for
      treating high-risk patients with NSTE ACS who are scheduled for percutaneous
      coronary intervention (PCI). The Medline database was searched in February 2007
      to retrieve relevant articles. Additional articles were obtained from the
      reference lists of retrieved articles, as well as from recent scientific meetings
      and company websites. FINDINGS: Results of the ISAR-REACT 2 trial indicate that
      administration of abciximab provides significant benefit for high-risk patients
      with NSTE ACS undergoing PCI; clopidogrel alone is not enough. In preliminary
      results of the ACUITY trial, glycoprotein IIb/IIIa inhibitor administration
      produced an incremental increase in bleeding events but a reduction in ischemic
      events; there was a trend to better outcomes with upstream administration, even
      short-term. Moreover, in the cohort of patients who underwent PCI, the composite
      ischemic endpoint was significantly lower with routine upstream glycoprotein
      IIb/IIIa inhibitor. Finally, results of the EVEREST pilot study, a mechanistic
      study evaluating epicardial and tissue level perfusion and cardiac troponin I
      release, significantly favored upstream administration of tirofiban over
      downstream glycoprotein IIb/IIIa inhibitor for high-risk patients with NSTE ACS
      undergoing PCI. Moreover, high bolus dose tirofiban or abciximab administered
      just before PCI produced similar effects on angiographic outcome and cardiac
      troponin I release. CONCLUSIONS: Recent and emerging evidence is clarifying the
      role of glycoprotein IIb/IIIa inhibitors in treating high-risk patients with NSTE
      ACS and indicates that these agents are of greatest benefit when given early.

PMID- 17559722
TI  - Immunomodulating drugs in multiple sclerosis: compliance, satisfaction and
      adverse effects evaluation in a German multiple sclerosis population.
AB  - OBJECTIVE: To assess the compliance, satisfaction and adverse effects of
      immunomodulating drugs in a German multiple sclerosis (MS) population. RESEARCH
      DESIGN AND METHODS: A standardised, anonymous questionnaire was sent to the 1985
      members with MS of the Berlin section of the German Multiple Sclerosis
      Association. Patients were questioned with regards to sociodemographic data, MS
      related topics, therapy, adverse effects and compliance. The response rate was
      51.1%, from which 681 patients were selected who were experienced in therapy with
      interferon beta 1a or 1b or glatiramer acetate. RESULTS: Most participants were
      treated with beta-interferons and only one-third with glatiramer acetate.
      Patients were moderately satisfied with their medication. Approximately 75.5% of
      patients had used the medication for longer than 2 years, especially those with a
      relapsing-remitting course (RRMS). Around one-third of all participants had their
      immunomodulating drug changed, mostly only once. The main reasons for
      discontinuation of the therapy were adverse effects, physician's recommendation
      and lack of treatment effect. Mood-related adverse effects (e.g., depression),
      fever and pain were perceived as most disturbing. Regression analysis revealed
      that dependence on a wheelchair and a secondary progressive course predicted a
      low compliance to treatment. CONCLUSION: Treating MS is a challenge and to
      positively influence the course of the disease it is necessary to administer
      medication in a constant manner. Our data showed a moderate compliance and
      satisfaction with the immunomodulating medication. Adverse effects and perceived
      lack of treatment effect were reasons for discontinuation of therapy. To increase
      compliance and satisfaction with treatment, adequate information about MS, the
      therapeutic options, handling of medication, side-effects and their management
      are necessary. Additionally, realistic therapeutic aims should be discussed with
      the patients.

PMID- 17559723
TI  - The effect of intravitreal triamcinolone on intraocular pressure.
AB  - OBJECTIVE: To evaluate the effect of triamcinolone acetonide (ITA) on intraocular
      pressure (IOP) following intravitreal injection, and, in those patients who
      experience post-injection elevation of IOP, to determine the time course, effect
      of multiple injections, and risk factors for the pressure rise. METHODS: A
      retrospective chart review of 85 consecutive patients who received ITA (0.1 mL of
      40 mg/mL solution) at the University of Texas South-western Medical Center
      between January 2002 and April 2004 was performed. Patient age, history of open
      angle glaucoma (OAG), previous intraocular surgery, prior steroid exposure, type
      of retinal pathology treated, pre- and post-injection IOP, and post-injection
      glaucoma medications were tabulated. Patients with previous exposure to topical,
      intraocular or systemic steroids, and those without at least 16 weeks of follow
      up were excluded. A student's paired t-test was used for statistical analysis.
      RESULTS: Seventy-seven eyes of 70 patients were included. Forty-eight eyes
      (62.3%) experienced an increase in IOP of at least 5 mmHg. Twenty-five eyes
      (32.5%) experienced elevation in IOP of 5-9 mmHg, and 23 eyes (29.9%) experienced
      an increase in IOP of > or = 10 mmHg during the review period. The mean time for
      elevations of 5-9 mmHg and > or = 10 mmHg to occur following injection were 6.9
      weeks and 8.8 weeks, respectively. Fifty percent of eyes (3/6) in patients with
      OAG experienced a maximum IOP level of > 30 mmHg. Of all eyes with IOP elevation
      following injection, 32.5% required topical glaucoma therapy. Thirteen eyes
      received a second ITA injection. All eight eyes with IOP elevation after the
      first injection experienced another rise in IOP after the second. Of the five
      eyes which had no rise in IOP after the first injection, four had no rise after
      the second. At the final visit, 50% of eyes (3/6) with OAG required additional
      glaucoma medication compared to baseline. No patients required surgery for IOP
      control during the period under review. CONCLUSIONS: ITA is frequently associated
      with a significant elevation in IOP, typically within the first 2-months after
      injection. Most patients who do not have an elevated IOP after an initial
      injection will not experience a pressure rise after an additional one. About one
      third will require topical glaucoma therapy for IOP control. Patients with OAG
      may be more difficult to control and require a longer duration of therapy. The
      inconsistent post-injection follow-up visit intervals among patients in this
      retrospective review may have affected our results, as some patients with maximum
      IOP changes may have been missed between office visits. In addition, practice
      patterns among treating physicians typically differ as to thresholds for the
      treatment of elevated IOP. A randomized, prospective, controlled trial could
      better address these issues.

PMID- 17559724
TI  - Post-thymectomy combined treatment of prednisone and tacrolimus versus prednisone
      alone for consolidation of complete stable remission in patients with myasthenia
      gravis: a non-randomized, non-controlled study.
AB  - BACKGROUND: Thymectomy is a standard treatment of myasthenia gravis (MG).
      Immunomodulating agents are frequently given during the post-thymectomy latency
      period until complete remission is fully consolidated. OBJECTIVE: A single
      centre, non-randomized, non-controlled study was conducted to compare rates of
      complete stable remission (CSR) to post-thymectomy early treatment with
      prednisone alone or prednisone combined with tacrolimus, in 80 patients with MG.
      METHODS: Thirty-nine consecutive patients underwent elective transsternal
      extended thymectomy in 1997-1999 and received prednisone alone (1.5 mg/kg/day)
      postoperatively, whereas 41 patients operated on in 2000-2002 received prednisone
      combined with tacrolimus (0.1 mg/kg per day b.i.d. starting 24 hours after
      thymectomy). RESULTS: The mean follow-up was 59 months (SD 32.9) in the
      prednisone group and 35.9 months (SD 17.1) in the tacrolimus group (p = 0.003).
      CSR was achieved in 47.5% of patients in the tacrolimus group and in 41.0% in the
      prednisone group (p = 0.60). The estimated median follow-up to obtain a CSR in
      non-thymomatous MG was 38.2 months (95% confidence interval [CI] 30.1-46.4
      months) for the tacrolimus group and 64.6 months (95% CI 50.9-78.2 months) for
      the prednisone group, and in patients with hyperplasia, 32.2 months (95% CI 23
      41.5 months) and 62.9 months (95% CI 45.7-80.1 months), respectively (log-rank
      test, p = 0.03). The behavior of the two study groups stratified by thymic
      histology were significantly different (log-rank test, p = 0.006). CONCLUSIONS:
      Post-thymectomy administration of tacrolimus combined with prednisone was more
      effective than prednisone alone for the consolidation of CSR in a substantially
      shorter period of time in patients with MG.

PMID- 17559725
TI  - The effect of infliximab on oxidative stress in chronic inflammatory joint
      disease.
AB  - OBJECTIVE: To evaluate infliximab effect on oxidative stress in active chronic
      inflammatory joint disease. PATIENTS AND METHODS: The study population comprised
      12 patients: five with ankylosing spondylitis, five with rheumatoid arthritis and
      two with psoriatic arthritis. At the time of the study all patients were divided
      into two groups: (i) seven active patients and (ii) five inactive patients
      according to the accepted criteria that define activity of disease for each of
      the diseases. C-reactive protein and erythrocyte sedimentation rate were
      measured. Patient's Global Assessment of the Disease (PGA), Bath Ankylosing
      Spondylitis Disease Activity Index (BASDAI) for ankylosing spondylitis patients
      and Disease Activity Score (DAS 28) for rheumatoid arthritis patients) were used
      for assessment of disease activity. Patients with active chronic inflammatory
      joint disease were introduced into the infliximab therapy programme. RESULTS:
      Infliximab effects were evaluated after 6 weeks of treatment as changes in the
      quantity of lipid peroxidation products, protein carbonyl groups, reduced
      glutathione content, glutathione peroxidase, catalase and superoxide dismutase.
      CONCLUSIONS: Our results revealed that: (i) infliximab has antioxidative
      properties, (ii) chronic inflammatory joint patients show high levels of
      oxidative injury, and (iii) oxidative stress is more intense in active disease
      group than in the inactive disease group.

PMID- 17559726
TI  - Pharmacotherapy of generalized anxiety disorder: results of duloxetine treatment
      from a pooled analysis of three clinical trials.
AB  - OBJECTIVE: Duloxetine is a serotonergic noradrenergic reuptake inhibitor with
      demonstrated efficacy in each of three independent studies for treatment of
      adults with generalized anxiety disorder (GAD). A pooled dataset from all
      completed trials is provided here to show the most likely clinical outcomes
      associated with duloxetine treatment for GAD. RESEARCH DESIGN AND METHODS: Data
      were summed at the individual patient level from three double-blind, placebo
      controlled trials of duloxetine treatment: two were 10-week flexible-dose 60-120
      mg/day and one was 9-week fixed dose 60 or 120 mg/day. Inclusion/exclusion
      criteria were consistent across studies. MAIN OUTCOME MEASURES: Efficacy measures
      included the Hamilton Anxiety Scale (HAMA) and Sheehan Disability Scale (SDS).
      Adverse events were queried at every visit in each study. RESULTS: Patients were
      randomly assigned to duloxetine (n = 668) or placebo (n = 495) treatment. Mean
      age was 42.4 years; 65% were female. Duloxetine-treated patients improved
      significantly more from baseline to endpoint on HAMA total score (mean = -11.1
      points) compared with placebo-treated patients (mean = -8.0 points, p < or =
      0.001). On the SDS global functioning score, patients in the duloxetine group had
      a mean improvement from baseline of 46% compared with 25% in the placebo group (p
      < or = 0.001). Nausea was the most common of twelve treatment-emergent adverse
      events that occurred in the duloxetine group. LIMITATIONS: Pooled studies were
      not for long-term treatment and did not include patients with comorbid
      psychiatric conditions. CONCLUSIONS: In this sample of more than 1100 patients,
      duloxetine was efficacious for reducing anxiety severity and for increasing
      patients' overall role functioning in GAD.

PMID- 17559727
TI  - Valproate in the treatment of PTSD: systematic review and meta analysis.
AB  - OBJECTIVE: Anticonvulsants are used in clinical practice for the treatment of
      PTSD. However, a systematic investigation of their effects in the treatment of
      PTSD is currently lacking from the literature. Our aim is to review and appraise
      the evidence for the use of the anticonvulsant valproate for the treatment of
      PTSD. METHODS: We performed a systematic review and meta-analysis of the
      literature where valproate was used for the treatment of PTSD. Studies of
      treatment of PTSD with valproate were located using a search protocol which was
      applied to the electronic databases CINAHL, EMBASE, MEDLINE and PSYCHINFO. A
      search of the National PTSD Centre Pilots Database and of the Cochrane
      Collaboration Depression, Anxiety and Neurosis Controlled Trials Register
      (CCDANCTR) were also conducted. FINDINGS: We only found one single-blinded study,
      four open-label studies and three case reports. These data do not allow for
      robust conclusions because of the design of the studies which are of limited
      patient number and open to bias. However, the studies reported that valproate was
      generally effective for the treatment of symptoms of PTSD by reducing
      hyperarousal, improving irritability and anger outbursts and improving mood.
      CONCLUSIONS: The limited evidence base suggests that valproate can be effective
      as a monotherapy for the treatment of both PTSD and mood symptoms. A double blind
      controlled study should be the next step to robustly study the efficacy of
      valproate on the treatment of PTSD.

PMID- 17559728
TI  - Use of in-office anesthesia during non-surgical radiofrequency collagen
      denaturation for stress urinary incontinence.
AB  - OBJECTIVE: Clinical trials have demonstrated the safety and efficacy of non
      surgical, transurethral radiofrequency (RF) collagen denaturation for treating
      female stress urinary incontinence (SUI) due to hypermobility. Women in those
      trials were anesthetized using intravenous conscious sedation. This multicenter
      trial aimed to demonstrate the feasibility, safety, and efficacy of an oral
      sedation and local anesthetic regimen in performing RF collagen denaturation.
      DESIGN AND METHODS: This single-arm study enrolled 33 women, each diagnosed with
      SUI due to hypermobility, at three United States sites (private physician
      offices). All women were pretreated with an oral sedative (diazepam) and
      antibiotic (quinolone) and underwent a bilateral peri-urethral block using 10 cc
      total of 2% lidocaine. Non-surgical, transurethral RF collagen denaturation was
      then performed. MAIN OUTCOME MEASURES: The feasibility of the in-office
      anesthetic regimen was determined based on the number of RF collagen denaturation
      treatments completed without conversion to intravenous conscious sedation. To
      assess the patients' subjective level of pain, a visual analog scale (VAS) (0 =
      no pain; 10 = terrible pain) was completed by each patient immediately before
      discharge. RESULTS: The in-office anesthetic regimen allowed for treatment
      completion in all patients (100% feasibility). On the VAS, 42% of the women rated
      their pain as 0; the mean pain score was 1.4 (SD 1.8). One woman (3% prevalence)
      experienced two clinically minor adverse events not conclusively related to the
      anesthetic regimen; both resolved spontaneously without treatment. CONCLUSIONS:
      The results of this trial were similar to those of larger, sham-controlled
      studies using intravenous conscious sedation and showed non-surgical RF collagen
      denaturation to be feasible, safe, and effective when performed using in-office
      anesthesia.

PMID- 17559729
TI  - Duloxetine versus escitalopram and placebo: an 8-month, double-blind trial in
      patients with major depressive disorder.
AB  - BACKGROUND: Duloxetine and escitalopram were compared in an 8-month, randomized,
      double-blind, placebo-controlled trial in adult outpatients meeting DSM-IV
      criteria for major depressive disorder (MDD). The results regarding the primary
      objective of the study (onset of antidepressant action) have been previously
      published. The current paper focuses on the longer-term (8-month) comparisons of
      efficacy and safety between duloxetine and escitalopram. RESEARCH DESIGN AND
      METHODS: Upon completion of the 8-week, fixed-dose, placebo-controlled, acute
      treatment phase (duloxetine 60 mg/day (n = 273), escitalopram 10 mg/day (n =
      274), placebo (n = 137)), patients remaining in the duloxetine (n = 188) and
      escitalopram (n = 208) groups were eligible for double-blind dose increases
      (duloxetine to 120 mg/day, escitalopram to 20 mg/day), and placebo non-responders
      were eligible for double-blind rescue to active drug. MAIN OUTCOME MEASURES:
      Efficacy was primarily assessed using the HAMD(17). Safety/tolerability
      assessments included spontaneously reported adverse events (AEs), overall rates
      and reasons for discontinuation, laboratory analyses, and vital signs. RESULTS:
      Both drugs demonstrated similar remission rates over the course of the study,
      with the probability of remission reaching 70% (duloxetine) and 75%
      (escitalopram) at 8 months (p = 0.44). Similar improvement was observed for both
      duloxetine and escitalopram on efficacy measures with the exception of the sleep
      subscale of the HAMD(17), wherein escitalopram had a statistically significant
      advantage over duloxetine in improving sleep. Over the entire 8-month study,
      discontinuation rates differed significantly for duloxetine (62%) compared with
      escitalopram (55%; p = 0.02). Rates of discontinuation due to AEs did not differ
      significantly between duloxetine (12.8%), escitalopram (12.0%), and placebo
      (10.2%) (p > 0.05 all pairwise comparisons). AEs associated with duloxetine
      tended to emerge early in treatment (e.g., nausea, dry mouth), whereas AEs
      associated with escitalopram tended to emerge later in treatment (e.g., diarrhea,
      weight increase). The incidence of sustained hypertension was similar between
      drugs (1.5 vs. 1.1% patients for duloxetine and escitalopram, respectively).
      Statistically significant drug differences were identified in the mean changes
      from baseline to study endpoint for pulse (+3.05 beats per minute (bpm),
      duloxetine; -0.89 bpm, escitalopram; p < 0.001) and systolic blood pressure
      (+3.73 mmHg, duloxetine; +0.31 mmHg, escitalopram; p < 0.05), but not diastolic
      blood pressure (+0.81 mmHg, duloxetine; -0.24 mmHg, escitalopram; p = 0.27). At 8
      months, mean change in weight was significantly higher for escitalopram compared
      with duloxetine (+0.61 kg, duloxetine; +1.83 kg, escitalopram; p < 0.05),
      however, the incidence of treatment-emergent abnormal weight gain (> or = 7%
      increase in weight from baseline) was similar between drugs and was significantly
      greater for both duloxetine and escitalopram compared with placebo. LIMITATIONS:
      Because so few patients on placebo (n = 15), in comparison to duloxetine (n =
      104) or escitalopram (n = 123), completed the entire 8-month study, the power to
      detect a difference between the active treatments and placebo after 8 weeks was
      significantly decreased and very likely insufficient. CONCLUSION: Throughout the
      8-month study, similar improvement was observed for both duloxetine and
      escitalopram on most efficacy measures with the exception of the sleep subscale
      of the HAMD(17). Drug differences were identified in safety/tolerability
      measures.

PMID- 17559730
TI  - Stratum corneum pharmacokinetics of the anti-fungal drug, terbinafine, in a novel
      topical formulation, for single-dose application in dermatophytoses.
AB  - OBJECTIVE: The stratum corneum (SC) pharmacokinetics of terbinafine following
      single-dose administration of a novel cutaneous solution (film-forming solution,
      FFS) containing terbinafine hydrochloride and a film-forming agent, was
      investigated in three studies. Terbinafine 1% cream (Lamisil) was included as a
      benchmark in two of these studies. RESEARCH DESIGN AND METHODS: Drugs were
      applied to areas of the back, and skin strips were taken from defined areas at
      baseline and from 1 to 312 h after application. Samples were analysed using
      validated liquid chromatography/mass spectrometry. RESULTS: The residence time of
      the film on the skin was up to 72 h after application (up to 12 h for the 1%
      cream). After application of terbinafine FFS, 30% of the total amount of drug
      delivered into the SC occurred during the first 2 h, 31% from 2-12 h, and 39%
      thereafter. The C(max) was observed as early as 1.5 h (t(max)). SC levels were
      still detected after 13 days (24 ng/cm(2)) (t(1/2)) was 162 h). Terbinafine 1%
      cream showed a similar t(max) (2 h) with a lower C(max) than terbinafine 1% FFS,
      and mean SC levels after 7 days of treatment were 46 ng/cm(2) (day 13). The
      t(1/2) was 68 h. Washing at 30 min removed 86% of the film still present on the
      surface; the decrease of terbinafine concentration in the SC was 84%. A later
      washing at 12 h removed 73% of the film in comparison to non-washed skin and
      induced a decrease in the terbinafine content in the SC of 27%. CONCLUSIONS: The
      SC pharmacokinetic profile of terbinafine 1% FFS indicates that this novel
      formulation is efficient in delivering high amounts of terbinafine to the skin
      for a prolonged time and supports its use in the treatment of dermatophytoses
      with a single application.

PMID- 17559731
TI  - Risk of recurrent emergency department visits or hospitalizations in children
      with asthma receiving nebulized budesonide inhalation suspension compared with
      other asthma medications.
AB  - OBJECTIVE: To examine whether nebulized budesonide inhalation suspension
      treatment reduces asthma-related emergency department visit/hospitalization
      recurrence risk in children compared with other asthma medications, particularly
      non-nebulized inhaled corticosteroids. RESEARCH DESIGN AND METHODS: Longitudinal,
      retrospective claims analysis of data from a managed care organization database
      in the United States (July 1, 2000-June 30, 2002). Participants were children
      aged < or = 8 years with an asthma diagnosis and asthma-related emergency
      department visit or hospitalization (index event). Asthma medication use,
      evaluated by asthma-related prescriptions < or = 30 days after the index event,
      determined treatment groups. MAIN OUTCOME MEASURE: Emergency department
      visit/hospitalization recurrence risk from post-index day 31-180 across treatment
      groups. RESULTS: Of 10,176 patients with an index event, 13% experienced a post
      index recurrence. For patients receiving asthma prescriptions < or = 30 days
      after the index event, those receiving budesonide inhalation suspension showed a
      significant reduction in emergency department visit/hospitalization recurrence
      risk compared with those not prescribed this treatment (adjusted hazard ratio,
      0.71; 95% confidence interval, 0.57-0.89). For patients receiving asthma
      controller medication in the post-index period, those receiving budesonide
      inhalation suspension had a significantly lower recurrence risk than patients
      receiving prescriptions for other controller medications (hazard ratio, 0.71; 95%
      confidence interval, 0.52-0.97). Recurrence risk was significantly reduced (53%)
      in patients receiving budesonide inhalation suspension prescriptions compared
      with non-nebulized inhaled corticosteroid prescriptions (hazard ratio, 0.47; 95%
      confidence interval, 0.28-0.78). CONCLUSION: For children aged < or = 8 years,
      budesonide inhalation suspension treatment after an asthma-related emergency
      department visit/hospitalization was associated with a significantly reduced risk
      of recurrence compared with other asthma medications and with non-nebulized
      inhaled corticosteroids. Because this was an observational study, results should
      be interpreted cautiously. However, this study allowed evaluation of treatment in
      real-world practice settings not often included in clinical trials.

PMID- 17559732
TI  - Physician and patient perceptions on the use of vitamin D and calcium in
      osteoporosis treatment: a European and Latin American perspective.
AB  - OBJECTIVE: Although osteoporosis treatment guidelines include recommendations for
      calcium and vitamin D intake, routine use of adequate supplementation often is
      low. This study explored the attitudes of physicians and patients towards vitamin
      D and calcium and patient use of both supplements. METHODS: A survey of randomly
      selected physicians in the United Kingdom, Mexico, and Austria, and the first
      seven eligible women with osteoporosis from each of their practices, was
      conducted. Physicians were asked to rate the importance of vitamin D and calcium
      in osteoporosis management on a scale of 1 to 10 (1 = not important at all, 10 =
      extremely important) and to estimate use of calcium and vitamin D supplements by
      their patients. Patients were asked about their own use of vitamin D and calcium,
      and their perceptions regarding these supplements. RESULTS: Altogether 151
      physicians (50 in Austria, 51 in the UK, and 50 in Mexico), and 910 osteoporosis
      patients (350 in Austria, 212 in UK, and 348 in Mexico) completed telephone
      surveys. Approximately, 86%, 28%, and 46% of physicians rated importance of
      vitamin D and calcium as being 9 or 10 in Austria, UK, and Mexico, respectively.
      Overall, 50% of patients reported taking calcium and vitamin D supplements (47%
      of these on a daily basis and 46% on a regular basis), and 19% of patients
      reported that they had no discussions with their physicians about calcium, while
      39% reported no discussion about vitamin D. CONCLUSIONS: Despite the recognition
      by physicians and patients that vitamin D and calcium are important for bone
      health, only a small proportion of patients regularly take supplements. This is
      the case even when vitamin D and calcium supplements are provided free with
      osteoporosis drug prescriptions, as occurs in Austria. However, these results
      rely on patient self-report of compliance which can lead to overestimation. In
      addition this study's participants may not be representative of other patient
      populations. This study provides additional evidence that compliance with
      treatment guidelines is suboptimal, and highlights the need for further study to
      explore the discrepancy between the highly perceived importance of vitamin D and
      calcium and the low use of both supplements, and to improve use among
      osteoporosis patients.

PMID- 17559734
TI  - The effect of adjunctive mood stabilizers on antipsychotic utilization pattern
      and health resource utilization for Medicaid enrollees with schizophrenia.
AB  - BACKGROUND: Prescribing adjunctive mood stabilizers to manage schizophrenia is
      prevalent, despite the lack of substantial evidence to support the long-term use
      of this treatment regimen. OBJECTIVE: The objective of this study was to assess
      the impact of using adjunctive mood stabilizers on antipsychotic utilization,
      total health expenditures, inpatient hospitalizations, long-term care stays, and
      emergency room (ER) visits for patients with schizophrenia. METHODS: Georgia
      Medicaid claims from 1999 through 2001 were analyzed to identify recipients
      diagnosed with schizophrenia (International Classification of Diseases, Ninth
      Revision, Clinical Modification [ICD-9-CM]: 295. XX). The treatment groups
      consisted of subjects who received combination therapy of mood stabilizers and
      antipsychotics (including both atypical and typical medications), while the
      comparison group consisted of subjects who were on antipsychotic medications
      without exposure to the mood stabilizers under investigation. Four treatment
      groups (valproate, lithium, carbamazepine, and combination mood stabilizer
      therapy) were formed based on the mood stabilizers patient received. Differences
      in annual health care use and expenditures were estimated between propensity
      score matched treatment and comparison groups controlling for comorbidity, prior
      utilization, demographic, and health provider specialty. RESULTS: During the 1
      year observation period, subjects in treatment groups filled an average of 200
      days supply of adjunctive mood stabilizers. These adjunctive mood stabilizer
      recipients had significantly longer antipsychotic treatment durations than the
      subjects who did not have exposure to mood stabilizers (valproate + antipsychotic
      vs. antipsychotic only, net difference: 56.47 days, p < 0.0001; lithium +
      antipsychotic vs. antipsychotic only, net difference: 90.25 days, p < 0.0001;
      carbamazepine + antipsychotic vs. antipsychotic only, net difference: 41.27 days,
      p = 0.0439; multiple mood stabilizers + antipsychotic vs. antipsychotic only, net
      difference: 83.14 days, p < 0.0001). The intensive pharmacotherapy associated
      with treatment groups resulted in $900-$1300 higher pharmacy costs than the
      comparison groups (valproate + antipsychotic vs. antipsychotic only, net
      difference: $1218.43, p < 0.0001; lithium + antipsychotic vs. antipsychotic only,
      net difference: $985.79, p = 0.0015; carbamazepine + antipsychotic vs.
      antipsychotic only, net difference: $911.63, p = 0.0497; multiple mood
      stabilizers + antipsychotic vs. antipsychotic only, net difference: $1281.91, p <
      0.0047). However, there were no statistically significant differences for total
      health expenditures, hospitalizations, emergency room visits, and nursing home
      admissions between propensity-matched treatment and control groups. CONCLUSIONS:
      There were no differences in health care costs or utilization of ER, long-term
      care, and inpatient services between schizophrenia patients who did and did not
      receive adjunctive mood stabilizer; however, longer antipsychotic treatment
      durations were observed in patients receiving adjunctive mood stabilizers.
      Interpretation of these results is limited by the unknown selection bias between
      the treatment and the comparison groups and the relatively small number of
      patients in some treatment groups. The development of a better-controlled study
      to further evaluate this treatment regimen is warranted.

PMID- 17559733
TI  - Once-daily sitagliptin, a dipeptidyl peptidase-4 inhibitor, for the treatment of
      patients with type 2 diabetes.
AB  - OBJECTIVE: Sitagliptin, an oral, potent, and selective dipeptidyl peptidase-4
      (DPP-4) inhibitor was evaluated as once-daily monotherapy in a 12-week
      randomized, double-blind, placebo-controlled, parallel group, dose-ranging study.
      Additionally, the glycemic response to sitagliptin 100 mg daily was evaluated as
      a once-daily (100 mg once-daily) or twice-daily (50 mg twice-daily) dosing
      regimen. RESEARCH DESIGN AND METHODS: In a multinational, double-blind,
      randomized, placebo-controlled, parallel-group, dose-range finding study, 555
      patients, 23-74 years of age, with HbA(1c) of 6.5-10.0% were randomized to one of
      five treatment groups: placebo, sitagliptin 25, 50 or 100 mg once-daily, or
      sitagliptin 50 mg twice-daily for 12 weeks. The efficacy analysis was based on
      the all-patients-treated population using an ANCOVA model. RESULTS: Mean baseline
      HbA(1c) ranged from 7.6 to 7.8% across treatment groups, with 29% of all patients
      with values < or =7%. After 12 weeks, treatment with all doses of sitagliptin
      significantly (p < 0.05) reduced HbA(1c) by -0.39 to -0.56% and fasting plasma
      glucose by -11.0 to -17.2 mg/dL relative to placebo, with the greatest reduction
      observed in the 100-mg once-daily group. Mean daily glucose was significantly (p
      < 0.05) reduced by -14.0 to -22.6 mg/dL with all doses of sitagliptin relative to
      placebo. HOMA-beta was significantly (p < 0.05) increased by 11.3-15.2 with all
      sitagliptin doses relative to placebo. QUICKI and HOMA-IR were not significantly
      changed with sitagliptin treatment. There were no significant differences
      observed between the sitagliptin 100 mg once-daily and 50 mg twice-daily groups
      for any parameter. For sitagliptin, the incidence of adverse events of
      hypoglycemia was low, with one event in each of the 25- and 50-mg once-daily and
      50-mg twice-daily treatment groups and two events in the 100 mg once-daily
      treatment group. There was no mean change in body weight with sitagliptin
      relative to placebo. Study duration may be a limitation because the extent of the
      glycemic response and the safety and tolerability may not have been fully
      elucidated in this 12-week study. CONCLUSION: Sitagliptin monotherapy improved
      indices of glycemic control compared to placebo and was generally well-tolerated
      in patients with type 2 diabetes. The glycemic response to treatment with
      sitagliptin 100 mg/day was similar between the sitagliptin 100-mg once-daily and
      50-mg twice-daily dose regimens.

PMID- 17559735
TI  - A randomized, controlled trial comparing darbepoetin alfa correction/maintenance
      dosing with weekly dosing for treating chemotherapy-induced anemia.
AB  - OBJECTIVE: To evaluate if a darbepoetin alfa correction/maintenance dosing
      regimen is non-inferior to a weekly regimen with respect to red blood cell
      transfusion requirements in patients with chemotherapy-induced anemia (CIA).
      RESEARCH DESIGN AND METHODS: In this randomized, active-controlled, double-blind
      phase 3 trial, CIA patients were randomized 1:1 to receive darbepoetin alfa in
      either a correction/maintenance schedule (4.5 microg/kg weekly for 4 weeks
      followed by 4.5 microg/kg every 3 weeks (Q3W)) or a weekly schedule (2.25
      microg/kg weekly). The primary endpoint was the transfusion incidence during
      weeks 1-16. Non-inferiority was to be concluded if the upper limit of the 95%
      confidence interval (CI) of the difference in transfusion incidence between
      treatment groups was below 12.5%. Hematologic responses and safety profiles were
      also compared. RESULTS: Transfusion incidence (95% CI) during weeks 1-16 was 37%
      (32-42) and 38% (32-43) in the weekly and correction/maintenance groups,
      respectively. The difference (95% CI) in transfusions was 0.4% (-7.0 to 7.8),
      demonstrating non-inferiority between treatment groups. Similar percentages in
      both groups achieved and maintained hemoglobin in a target range of 11-13 g/dL
      and had clinically meaningful FACT-F score improvements. The median (range) time
      to hemoglobin response was 10 (1-17) weeks and 12 (2-17) weeks in the weekly and
      correction/maintenance groups, respectively. Both groups had similar safety
      profiles. CONCLUSIONS: A correction/maintenance schedule with its initial two
      fold higher weekly dosing and subsequent Q3W dosing yielded outcomes similar to
      those observed with a weekly schedule. Although correction/maintenance dosing
      provided no incremental clinical benefit, Q3W dosing could provide benefits of
      convenience and facilitate patient compliance.

PMID- 17559736
TI  - The safety profile of moxifloxacin and other fluoroquinolones in special patient
      populations.
AB  - BACKGROUND: Fluoroquinolones, including ciprofloxacin, levofloxacin,
      gemifloxacin, and moxifloxacin, represent a major advance in the development of
      antimicrobial agents. They offer significant activity against Gram-negative
      pathogens, while more advanced generation fluoroquinolones including
      levofloxacin, gemifloxacin, and moxifloxacin are significantly active against
      Gram-positive (e.g., Streptococcus pneumoniae for some members of the class),
      typical, atypical, and anaerobic pathogens. Fluoroquinolones have a
      pharmacokinetic/pharmacodynamic profile that exhibits concentration-dependent
      killing and good oral absorption, allowing for once-daily dosing. OBJECTIVE:
      Review of data from fluoroquinolone studies, with an emphasis on the associated
      rare, but potentially clinically important, adverse events in specific patient
      populations. Review of clinical efficacy is included where relevant to the topic
      under discussion. METHODS: A literature search was conducted using terms
      including fluoroquinolones, moxifloxacin, ciprofloxacin, levofloxacin,
      gatifloxacin, gemifloxacin, safety, adverse events, drug interactions, and
      pharmacokinetic parameters to identify literature providing information regarding
      the safety profile of specified fluoroquinolones in special patient populations
      (i.e., the elderly, patients with liver disease, kidney disease, glycemic
      disorder, those at risk for cardiovascular events). Although specific date
      criteria were not applied to the search, preference was given to more recent
      publications. Online databases searched include MEDLINE and EMBASE and relevant
      textbooks were utilized as well. FINDINGS: Fluoroquinolones, when used either as
      monotherapy or as combination therapy depending on their individual indications,
      attain adequate concentrations for treating infections in different target sites,
      including epithelial lining fluid, alveolar macrophages, skin, and
      gastrointestinal tissues. Overall, fluoroquinolones have predictable and mild-to
      moderate adverse-event profiles and are generally well tolerated. Findings of
      this review are limited by the availability of publications and case reports.
      CONCLUSIONS: Fluoroquinolones, are associated with rare, but clinically
      important, adverse events in special patient populations (including the elderly;
      those with hepatic, renal, or glycemic disorders; and those at risk for
      cardiovascular events). Recognition of differences in the clinical efficacy and
      safety profiles of fluoroquinolones in special patient populations should lead to
      better antimicrobial agent selection.

PMID- 17559737
TI  - Drug interaction assessment following concomitant administration of posaconazole
      and phenytoin in healthy men.
AB  - OBJECTIVE: Posaconazole is an extended-spectrum triazole antifungal agent for the
      treatment and prophylaxis of invasive fungal infections. This randomized, open
      label, parallel-group, multiple-dose study was conducted in healthy adult
      volunteers to assess the potential for a drug interaction between phenytoin and
      the posaconazole tablet formulation. METHODS: Subjects were randomly assigned for
      10 days to one of the following treatments: posaconazole (200 mg once daily),
      phenytoin (200 mg once daily), or posaconazole (200 mg once daily) and phenytoin
      (200 mg once daily). Blood samples were collected on days 1 and 10 for
      pharmacokinetic evaluation of posaconazole and phenytoin concentrations. RESULTS:
      A total of 36 healthy men enrolled in the study. On day 1, the maximum plasma
      concentration (C(max)) and area under the concentration-time curve calculated
      from time 0-24 h post-dose (AUC(0-24)) were unchanged upon co-administration. At
      steady state (day 10), co-administration of posaconazole with phenytoin resulted
      in 44% (p = 0.012) and 52% (p = 0.007) decreases in posaconazole C(max) and AUC(0
      24), respectively. These decreases in exposure corresponded with a 90% increase
      in steady-state clearance of orally administered posaconazole. Phenytoin C(max)
      and AUC(0-24) were not significantly altered upon co-administration of the two
      agents, 24% increase in C(max) (p = 0.196) and 25% increase in AUC(0-24) (p =
      0.212) values, although inter-subject variability was observed within this group.
      CONCLUSION: Because co-administration of phenytoin and posaconazole significantly
      reduces posaconazole exposure and increases phenytoin levels in some subjects,
      concomitant use of these agents should be avoided unless the benefit outweighs
      the risk.

PMID- 17559738
TI  - The complexity of medication regimens and test ordering for patients with
      diabetes from 1995 to 2003.
AB  - OBJECTIVE: Diabetes care has become increasingly complex. We set out to quantify
      recent trends in the complexity of medication regimens and test ordering for
      diabetes patients continuously enrolled in health plans affiliated with a large,
      regional US health maintenance organization, with representation in the South and
      Midwest. RESEARCH DESIGN AND METHODS: We provide descriptive trends analysis of
      overall diabetes care complexity (number of components [i.e., glucose, blood
      pressure, cholesterol control], number of medications/tests) from 1995 to 2003
      for adults with diabetes (N = 304,233). MAIN OUTCOME MEASURES: The main outcomes
      were (1) the proportion of patients receiving diabetes-related medications (blood
      glucose, blood pressure, and cholesterol control agents), (2) the average number
      of medications, (3) the proportion of patients receiving diabetes-related tests
      (glycosylated hemoglobin [HbA1c], urine microalbumin, and serum cholesterol), (4)
      and the average number of tests ordered within the first year that a patient had
      any indication of diabetes. RESULTS: The proportion of patients on cholesterol
      lowering drugs (18% --> 39%, p < 0.01) and blood pressure lowering drugs (51% -->
      62%, p = 0.04) rose significantly, while the proportion on glucose lowering drugs
      fell (76% --> 47%, p < 0.01). Among patients prescribed medications, the average
      total number of diabetes-related medications rose from 2.96 to 3.70 medications
      (p < 0.01) with smaller increases seen for glucose lowering (1.45 --> 1.65, p <
      0.01) and blood pressure lowering regimens (2.14 --> 2.51, p < 0.01), and no
      change for cholesterol lowering drugs (1.23 --> 1.19, p = 0.19). For laboratory
      tests, the proportion receiving cholesterol (40% --> 58%), and urine microalbumin
      (4% --> 18%) (all p's < 0.01) rose significantly, while the testing rates for
      HbA(1c) remained unchanged. The average total number of tests ordered per year
      increased significantly from 3.34 to 4.10 (p < 0.01) with more modest increases
      observed for individual tests. LIMITATION: Trends analyses are unadjusted for
      many clinical characteristics that might influence the complexity of diabetes
      care. CONCLUSIONS: Diabetes care grew more complex with the largest change in the
      number of patients receiving multi-component diabetes care. While the use of
      blood pressure and cholesterol lowering drugs rose overall, the proportion of
      patients using glucose lowering drugs declined and the average number of
      prescribed glucose lowering drugs did not increase in a clinically significant
      manner.

PMID- 17559739
TI  - The cost of treating ribavirin-induced anemia in hepatitis C: the impact of using
      recombinant human erythropoietin.
AB  - OBJECTIVE: Ribavirin-induced anemia (RIA) is a common adverse effect of chronic
      hepatitis C treatment. Studies have shown that the use of epoetin decreases the
      need for ribavirin dose reduction or discontinuation. The primary objective was
      to calculate the incremental cost of treating hepatitis C in those without versus
      with RIA, using either the strategy of ribavirin dose reduction/discontinuation
      or epoetin. The secondary objective was to calculate the incremental cost of
      using epoetin versus no epoetin to treat RIA, per ribavirin dose
      reduction/discontinuation averted. METHODS: Estimates from the literature and
      decision-analytic techniques were used to model treatment patterns and estimate
      the cost of managing RIA in genotype 1, 2, and 3 subjects. Sensitivity analyses
      were used to address uncertainty. RESULTS: Clinically significant RIA, a
      reduction in hemoglobin of > or = 2 g/dL (1.2 mmol/L), developed in 72% of
      patients in observational studies. The incremental cost of treating chronic
      hepatitis C decreased when employing the strategy of ribavirindose
      reduction/discontinuation to treat RIA, and increased by 5.7% (genotype 1) or
      34.4% (genotype 2 or 3), when using epoetin. Using one-way sensitivity analyses,
      the cost of using epoetin per ribavirin dose reduction/discontinuation averted
      was $39,579-$52,023. Generalizability may be limited to settings in which a
      similar proportion of patients develop RIA. CONCLUSIONS: The proportional cost of
      treating hepatitis C when using epoetin to treat RIA is significant in genotype 2
      or 3 patients. The cost of using epoetin per ribavirin dose
      reduction/discontinuation averted is substantial in patients with genotypes 1, 2,
      or 3; and varies with the probability of response to epoetin. These findings
      suggest that additional studies are warranted that will determine the effect of
      epoetin on treatment outcomes and its role as supportive therapy in patients with
      RIA.

PMID- 17559740
TI  - Will insomnia treatments produce overall cost savings to commercial managed-care
      plans? A predictive analysis in the United States.
AB  - OBJECTIVE: Research indicates that insomnia may contribute significantly to
      healthcare costs; however, information on the effects of treatments on costs has
      not been thoroughly published. This study presents predictive models that
      forecast, from the perspective of commercial managed care, the effects of
      insomnia medications in reducing overall medical costs. The main objectives of
      this study were to predict the level of cost savings associated with insomnia
      treatments, illustrate the variation in outcomes given underlying model
      assumptions, and assist managed-care policy-makers with the evaluation of
      medications routinely administered for insomnia. METHODS: Data on four primary
      efficacy measures: wake after sleep onset (WASO), sleep efficiency (SE), sleep
      onset latency (SOL) and total sleep time (TST) were abstracted from published
      clinical trial data for eszopiclone, indiplon, low-dose trazodone, ramelteon,
      zaleplon, zolpidem and zolpidem extended-release. Change in per-patient per-year
      (PPPY) healthcare costs in a single claims database was calculated for subjects
      taking zolpidem, zaleplon and low-dose trazodone using generalized linear model
      (GLM) techniques, controlling for baseline demographics and baseline costs.
      Change in costs for emerging insomnia medications was forecasted by imputing
      efficacy values for these drugs into the regressions. RESULTS: Using the accepted
      efficacy measure, WASO, zolpidem extended-release had the overall forecasted
      savings of -$1253 (CI: -$1404 to -$1404) PPPY compared to remaining treatments,
      whereas ramelteon cost an additional $348 (-$1280 to $584) PPPY. In three out of
      four cost-efficacy models, zolpidem extended-release had higher mean forecasted
      PPPY savings. CONCLUSION: This study examined cost effects of existing and
      emerging insomnia medications using models integrating clinical literature and
      medical claims within a statistical framework. The use of a single database may
      limit generalizability and models only address a 1-year period. Results suggest
      treatments can offer health plans direct cost savings, with amounts sensitive to
      variable and efficacy measures, potentially limited by those variables available
      in the claims database. Compared to other evaluated treatments, zolpidem extended
      release produced consistently higher predicted cost savings.

PMID- 17559741
TI  - Antiplatelet therapy for the prevention of recurrent stroke and other serious
      vascular events: a review of the clinical trial data and guidelines.
AB  - BACKGROUND: One strategy of reducing the burden of stroke is the prevention of
      recurrent stroke, following an initial ischaemic stroke or transient ischaemic
      attack (TIA) of arterial origin, by means of antiplatelet therapy. SCOPE: This
      review article surveys and discusses the current clinical trial data and
      guidelines for the use of antiplatelet therapy in the prevention of recurrent
      stroke/TIA of arterial origin (not stroke due to atrial fibrillation). Based on
      the latest available evidence, a new antiplatelet treatment algorithm for the
      long-term treatment of patients following atherothromboembolic ischaemic stroke
      or TIA is proposed. FINDINGS: Meta-analyses of randomised clinical trials in
      patients with TIA and ischaemic stroke of arterial origin indicate that, compared
      with control, the relative risk reduction (RRR) for recurrent stroke and other
      serious vascular events is 13% (95% confidence interval [CI] 6% to 19%) with
      aspirin, 13% (4% to 21%; p = 0.046) with dipyridamole and 34% (24% to 43%) with
      the combination of aspirin and dipyridamole. Compared with aspirin, the relative
      risk of recurrent stroke and other serious vascular events is reduced by 7.3%
      (95% CI -5.7% to 18.7%) with clopidogrel and 18% (9% to 26%; p = 0.0003) with the
      combination of aspirin and dipyridamole. The combination of aspirin and
      clopidogrel is not significantly more effective in preventing serious vascular
      events than clopidogrel alone (RRR 6.4%; -4.6% to 16.3%) in the long-term
      treatment of patients with previous ischaemic stroke and TIA, mainly because of a
      cumulative excess of bleeding complications. The relative risks and benefits of
      long-term treatment with clopidogrel and the combination of aspirin and
      dipyridamole are being compared in an ongoing large clinical trial (PRoFESS).
      Current Australian therapeutic guidelines for antiplatelet therapy among patients
      with TIA and ischaemic stroke of arterial origin have incorporated important new
      findings from recently published clinical trials and recommend aspirin or the
      combination of dipyridamole plus aspirin as the preferred long-term antiplatelet
      therapy. CONCLUSION: Whilst awaiting the results of the PRoFESS trial, the
      combination of dipyridamole plus aspirin is the preferred antiplatelet regimen to
      reduce the risk of recurrent vascular events among patients with TIA and
      ischaemic stroke of arterial origin.

PMID- 17559742
TI  - Prescriptions for vitamin D among patients taking antiresorptive agents in
      Canada.
AB  - BACKGROUND: Data on the rate of concomitant vitamin D use with antiresorptive
      medications are limited. Such information is important because vitamin D is
      indicated in patients with osteoporosis, including those receiving
      bisphosphonates, and there is evidence of inadequate use by these patients.
      OBJECTIVE: To examine prescription vitamin D utilization patterns. RESEARCH
      DESIGN AND METHODS: A retrospective analysis of patients aged > or = 65 years was
      conducted in a Canadian pharmacy-insurance organization (RAMQ) who received at
      least one prescription for an antiresorptive agent (i.e., alendronate,
      risedronate, raloxifene) from January 1, 1996, through December 31, 2003, and did
      not switch to any other agent during the 1-year post period. Data on
      prescriptions of vitamin D formulations on the RAMQ formulary (e.g.,
      alfacalcidol, calcitriol, cholecalciferol, doxercalciferol, ergocalciferol) were
      also captured. No data on generic or over-the-counter vitamin D preparations were
      available. A vitamin D and antiresorptive agent possession ratio (R(P)) was
      computed as: R(P) = SigmaD(SPVD) / SigmaD(SARR) where SigmaD(SPVD) = the sum of
      the days of supply with prescription vitamin D and SigmaD(SARR) = the sum of days
      of supply with alendronate, risedronate, or raloxifene A vitamin D and
      antiresorptive agent overlap ratio (R(0)) was computed as: R(0) =
      SigmaD(SPVDOARR) / SigmaD(SARR) where SigmaD(SPVDOARR) = the sum of days of
      supply of prescription vitamin D overlapping with alendronate, risedronate, or
      raloxifene, and SigmaD(SARR) = the sum of the days of supply with alendronate,
      risedronate, or raloxifene. RESULTS: A total of 46,226 antiresorptive treatment
      users were identified, > 90% of whom were women. A total of 17,151 (37.1%) had
      concomitant vitamin D prescriptions. The average duration of prescription therapy
      with alendronate, risedronate, or raloxifene was 247 days; and the mean duration
      of prescription vitamin D therapy was 83 days. Patients had a supply of vitamin D
      for 55% of days of antiresorptive agents therapy (R(P) = 0.55) and a vitamin D
      supply overlapping with 24% of their days on antiresorptive agents (R(o) = 0.24).
      Possession and overlap ratios were significantly higher in patients receiving
      once-weekly bisphosphonate prescriptions compared with once-daily regimens
      (bisphosphonates or raloxifene). Vitamin D prescriptions were also significantly
      more likely in patients receiving prescriptions for once-weekly bisphosphonates
      (odds ratio (OR) = 4.65; 95% CI = 4.29-5.05; p < 0.0001) and once-daily
      bisphosphonates (OR = 1.91; 95% CI = 1.76-2.07; p < 0.0001) compared with once
      daily raloxifene. CONCLUSIONS: Despite the benefits of vitamin D for
      osteoporosis, most patients ( approximately 63%) receiving prescriptions for
      antiresorptive agents were not taking vitamin D, indicating a substantial
      treatment gap. The study is limited by including data only on (1) pharmacy
      claims, which do not equate to patient behaviors, such as filling or refilling
      prescriptions and/or taking the medications; and (2) prescription (but not
      generic or over-the-counter) vitamin D formulations.

PMID- 17559743
TI  - Efficacy and comfort of olopatadine 0.2% versus epinastine 0.05% ophthalmic
      solution for treating itching and redness induced by conjunctival allergen
      challenge.
AB  - BACKGROUND: Olopatadine 0.2% (Pataday, Alcon Laboratories Inc., Fort Worth,
      Texas, USA) and epinastine 0.05% (Elestat, Inspire Pharmaceuticals, Inc., Durham,
      NC, USA) are topical ocular anti-allergic agents. Both are H(1)
      antihistamine/mast cell stabilizers indicated for the treatment of ocular itching
      associated with allergic conjunctivitis. OBJECTIVE: To compare the efficacy and
      comfort of olopatadine 0.2% with epinastine 0.05%, in the prevention of ocular
      itching associated with allergic conjunctivitis following conjunctival allergen
      challenge (CAC). RESEARCH DESIGN AND METHODS: This was a 7 week, four visit,
      double-masked, randomized, placebo-controlled CAC study. Visit 1 screened
      subjects for positive ocular allergic responses and Visit 2 confirmed those
      responses. At Visit 3, 92 subjects were randomized into one of four treatment
      groups to receive one drop of study medication in each eye: (1) olopatadine
      0.2%/placebo, (2) epinastine 0.05%/placebo, (3) olopatadine 0.2%/epinastine
      0.05%, (4) placebo/placebo. Subjects were challenged 12 h after drop instillation
      to evaluate duration of action. At Visit 4, subjects were challenged 5 min after
      drop instillation to evaluate onset of action. Drop comfort was assessed at Visit
      4. MAIN OUTCOME MEASURES; RESULTS: This article focuses on the results of the
      onset-of-action challenge (Visit 4). At Visit 4, ocular itching was assessed at
      3, 5, and 7 min and redness was assessed at 7, 15, and 20 min post-challenge.
      Drop comfort was assessed upon instillation, at 30s, and at 1, 2, and 5 min post
      instillation. Olopatadine 0.2%-treated eyes exhibited significantly lower mean
      ocular itching scores versus epinastine 0.05%-treated eyes at 5 (p = 0.024) and 7
      min (p = 0.003) post-challenge. Olopatadine 0.2%-treated eyes exhibited
      significantly lower mean redness scores versus epinastine 0.05%-treated eyes at
      all time points post-challenge (ciliary: p < or = 0.013, conjunctival: p < or =
      0.015, episcleral: p < or = 0.006). Olopatadine 0.2% was rated as significantly
      more comfortable than epinastine 0.05% at 1 min post-drop instillation (p =
      0.003). All adverse events were non-serious and unrelated to study medication.
      Although the CAC model reproduces allergic responses that are not environmentally
      induced, patients experience varying severities of responses as are seen in real
      world situations. CONCLUSION: Olopatadine 0.2% was superior to epinastine 0.05%
      in preventing ocular itching and redness at onset when induced by the CAC model.

PMID- 17559744
TI  - Cross-sectional analysis of adult diabetes type 1 and type 2 patients with
      diabetic microvascular complications from a German retrospective observational
      study.
AB  - OBJECTIVE: To obtain epidemiological data on the prevalence of predefined stages
      of diabetic microvascular complications from a representative cross-section of
      patients with existing microvascular complications of type 1 or type 2 diabetes
      in Germany. RESEARCH DESIGN AND METHODS: A cross-sectional, retrospective study
      of medical records of 705 type 1 and 1910 type 2 adult diabetic patients with a
      diagnosis of retinopathy and/or peripheral neuropathy and/or nephropathy before
      2002 and treated in 2002 in Germany. RESULTS: Of 376 patients with type 1
      diabetes having retinopathy, 59.3% had mild or moderate non-proliferative
      retinopathy without macular oedema, 27.1% had macular oedema, and 13.6% had
      severe retinopathy without macular oedema. In 862 patients with type 2 diabetes,
      the distribution of retinopathy/maculopathy classes was 56.8%, 35.5%, and 7.7%,
      respectively. Of 381 type 1 diabetes patients with observed peripheral
      neuropathy, 81.4% had sensorimotor neuropathy, 8.9% had diabetic foot conditions,
      and 9.7% had lower extremity amputations because of diabetes. In 1005 patients
      with type 2 diabetes, the distribution of neuropathy classes was 78.2%, 12.1%,
      and 9.7%, respectively. The proportions of patients with renal insufficiency in
      type 1 and type 2 diabetes groups were 15.3% versus 13.5%, respectively.
      CONCLUSIONS: The study suggests that there are considerable proportions of
      patients with progressive stages of microvascular complications related to type 1
      and type 2 diabetes in Germany. This underlines the importance of improvement of
      optimal quality of care and frequent screening for preventing late diabetic
      microvascular complications and the necessity of effective intervention
      strategies to tackle this major public health problem.

PMID- 17559745
TI  - Economic impact of gefitinib for refractory non-small-cell lung cancer: a Markov
      model-based analysis.
AB  - Few data are available on the economics of target therapy or refractory non-small
      cell lung cancer (NSCLC). OBJECTIVE: To determine the mean global management
      costs (MC) per patient treated with gefitinib for NSCLC, and the costs of the
      different management phases. METHOD: A Markov approach was used to model
      treatment costs in a cohort of 106 patients treated with gefitinib as part of a
      compassionate-use program (third-line treatment) in six public-sector teaching
      hospitals. The economic analysis adopted the health care payer's perspective, and
      only direct costs were taken into account. RESULTS: The mean duration of
      gefitinib treatment was 4.6 +/- 5.8 months (1-29 months); median survival was 4
      months, 1-year and 2-year survival rates were 12.3% and 4.7%, respectively. The
      mean total management cost was 39,979 euros +/- 20,279. The model showed that
      first- and second-line treatments accounted for respectively 29.5% and 44.1% of
      this cost, while gefitinib periods represented 10.7%, periods of remission 1.25%,
      and terminal care 14.5%. A sensitivity analysis showed that the price of
      gefitinib had little influence on the total cost. CONCLUSION: The cost of third
      line gefitinib therapy for NSCLC appears acceptable from the healthcare payer's
      perspective, but this needs to be confirmed in dedicated cost-effectiveness
      studies.

PMID- 17559746
TI  - An economic evaluation of vasoactive agents used in the United Kingdom for acute
      bleeding oesophageal varices in patients with liver cirrhosis.
AB  - OBJECTIVE: To conduct an economic evaluation of terlipressin, octreotide and
      placebo in the treatment of bleeding oesophageal varices (BOV) where endotherapy
      could be used concomitantly. METHODS: A discrete event simulation model was
      created with transition states: bleeding, no bleeding, no bleeding post
      transjugular intrahepatic portosystemic shunt, post-salvage surgery, and death.
      Efficacy data on survival, re-bleeding and control of bleeding were obtained from
      high quality studies reported in Cochrane meta-analyses. Baseline outcomes
      related to the course of disease and health-state utilities were derived from
      published sources. Vasoactive treatment costs and all related BOV costs were
      obtained from published UK sources. RESULTS: The average aggregated treatment
      cost per person for all medical interventions at 1 year was lower for
      terlipressin-treated patients (2623 pounds sterling) compared with those treated
      using octreotide (2758 pounds sterling) or placebo (2890 pounds sterling). The
      incremental analysis comparing terlipressin with octreotide and placebo using a
      cost per quality adjusted life year (QALY) and cost per life year gained (LYG)
      approach indicated that terlipressin was the dominant BOV treatment option (i.e.
      it cost less and it was more effective). Based on a maximum willingness to pay of
      20,000 pounds sterling/QALY terlipressin was more effective and cost-saving
      compared to octreotide and placebo for simulations ranging from 42 days to 2
      years. In point estimation analyses octreotide was dominant compared to placebo;
      however, probabilistic sensitivity analysis indicated that octreotide was
      unlikely to be cost-effective compared to placebo. CONCLUSIONS: The findings
      indicated that vasoactive treatment in BOV was cost-saving compared to no
      vasoactive treatment. Furthermore, terlipressin was the more cost-effective
      vasoactive treatment for BOV in cirrhotic patients.

PMID- 17559747
TI  - A review of the effects of antihyperglycaemic agents on body weight: the
      potential of incretin targeted therapies.
AB  - BACKGROUND: Current American Diabetes Association (ADA)/European Association for
      the Study of Diabetes (EASD) treatment guidelines recommend metformin (which does
      not promote weight gain) as the first-line antihyperglycaemic drug for patients
      with type 2 diabetes. However, when metformin fails, the recommended add-on
      treatment options (sulphonylureas, glitazones and basal insulin) can lead to
      significant weight gain. This article reviews the effect on body weight of
      current treatments for type 2 diabetes and discusses the potential impact of
      weight gain in this patient group. SCOPE: MEDLINE searches were performed to
      evaluate the prevalence and impact of changes in body weight in type 2 diabetes
      (articles published between January 1966 and August 2006) and the effects of
      sulphonylureas, glitazones, insulin, dipeptidyl peptidase-4 (DPP-4) inhibitors
      and incretin analogs on body weight in these patients (search between January
      2004 and September 2006). FINDINGS: Weight gain in general affects not only the
      physiological capability of patients with diabetes to achieve glycaemic control,
      but also their psychological well-being, quality of life and persistence with
      antihyperglycaemic treatment. Excess body weight and obesity in patients with
      diabetes are also associated with increased healthcare resource utilisation.
      Development of obesity is also associated with increased cardiovascular risk,
      although a link between drug-induced weight gain per se and increased
      cardiovascular risk has not been established. Initial clinical trial experience
      with the new oral DPP-4 inhibitors such as sitagliptin and vildagliptin suggests
      that these agents are weight-neutral, while providing improved glycaemic control
      when added to metformin. CONCLUSIONS: Because currently available add-on
      treatments can cause weight gain, physicians initiating add-on therapy in
      patients who can no longer achieve glycaemic control with metformin are faced
      with the problem of improving glycaemic control while causing weight gain.
      Initial clinical trial experience with oral DPP-4 inhibitors such as sitagliptin
      and vildagliptin suggest that these agents may represent an important oral
      treatment option for weight-neutral, glycaemic control when added to metformin.
      The new oral DPP-4 inhibitors, therefore, represent a potentially important
      addition to the oral treatment options currently available for the management of
      type 2 diabetes mellitus. Long-term clinical trials are now required to evaluate
      the relative risk/benefit profile of these drugs compared with the established
      antihyperglycaemic drug classes.

PMID- 17559748
TI  - Effect of NXY-059, a novel neuroprotectant, on the pharmacokinetics of a single
      dose of digoxin in healthy subjects.
AB  - OBJECTIVE: NXY-059 is a novel free-radical trapping neuroprotectant. Digoxin
      treatment is common in acute ischaemic stroke, the intended patient population
      for NXY-059. Since both digoxin and NXY-059 are eliminated primarily renally,
      with a substantial contribution by active renal secretion, and because digoxin
      has a narrow therapeutic window, this open, randomised, crossover, two-period
      study investigated whether NXY-059 affects the pharmacokinetics (PK) of digoxin.
      RESEARCH DESIGN AND METHODS: Twenty-two healthy subjects received 0.5 mg oral
      digoxin 2 h after the start of 60-h intravenous infusions of NXY-059 and placebo
      separated by a 14-day washout. Blood and urine were collected for 60 h. Digoxin
      concentrations were measured by a novel liquid chromatography-mass spectrometry
      assay. MAIN OUTCOME MEASURES: The ratio of the geometric mean (90% confidence
      interval) between NXY-059 and placebo for the digoxin area under the
      concentration-versus-time curve was 0.91 (0.83-0.99) and was within the
      predefined range for no interaction (0.80-1.25). No safety concerns were raised
      in the study. No serious adverse events were recorded. The most common adverse
      event was headache with similar frequencies in the two treatments. CONCLUSIONS:
      NXY-059 had no clinically significant effect on the PK of digoxin.

PMID- 17559749
TI  - An audit to determine the time taken to administer intravenous bisphosphonate
      infusions in patients diagnosed with metastatic breast cancer to bone in a
      hospital setting.
AB  - OBJECTIVE: Bone metastases can occur in many forms of cancer. More than two
      thirds of women with metastatic breast cancer may be affected by bone metastasis
      during the course of their disease. Bisphosphonates, which inhibit osteoclast
      mediated bone resorption, are an established standard of care for patients with
      bone metastases. For patients with cancer and bone metastases, bisphosphonates
      are associated with a significant reduction in skeletal-related events such as
      vertebral fractures, non-vertebral fractures as well as increasing the time to
      skeletal event. The purpose of this study was to quantify the current time
      involved in the administration of i.v. bisphosphonates and how this might impact
      on patient experience and cancer unit capacity. RESEARCH DESIGN AND METHODS: A
      pilot audit was initially conducted at the Royal Marsden Hospital (RMH), London
      (both Chelsea and Sutton sites), and was followed by audits at a further two UK
      hospital sites: Velindre Hospital, Cardiff and the Royal Surrey County Hospital,
      Guildford. The study was conducted between December 2005 and September 2006.
      RESULTS: Overall, 151 forms were completed. Of the total patients audited,
      approximately 71% had a diagnosis of breast cancer. Where data on the reason for
      attendance were collected (Velindre and the Royal Surrey County Hospital), over
      77% of patients attended hospital for the sole reason of having an i.v.
      bisphosphonate administered. The majority of patients (94%) required cannulation
      prior to infusion and, at the sites where this information was recorded (Royal
      Surrey County Hospital and Velindre Hospital), almost one-third of patients
      required two or more attempts before they were successfully cannulated. The time
      that the patients spent on the unit where the i.v. bisphosphonates were
      administered was greater for patients receiving pamidronate compared to those
      receiving zoledronic acid (2 h 36 min and 1 h 38 min, respectively). The
      magnitude of the difference was not as great as would be expected considering
      zoledronic acid should take one-sixth of the time to administer (Royal Marsden
      Hospital, pamidronate 1 h 29 min, zoledronic acid 18 min: Royal Surrey County
      Hospital, zoledronic acid 21 min: Velindre Hospital, pamidronate 1 h 42 min,
      zoledronic acid 17 min). CONCLUSIONS: I.v. bisphosphonates are accepted as
      standard clinical practice for the management of metastatic bone disease. They
      are often prescribed for long periods of time, so tolerability and patient
      acceptability are important factors in therapy. The administration of i.v.
      bisphosphonates contributes a substantial time burden for patients travelling to
      the hospital, considering that in most cases the purpose is for this treatment
      only. It also places a significant burden on hospital resources, creating
      capacity planning challenges. Receiving an i.v. bisphosphonate also has other
      disadvantages associated with it, such as the need for patients to undergo
      repeated cannulation. Service redesign, such as home administration of i.v.
      bisphosphonates, could help to overcome issues highlighted in this audit. The use
      of oral alternatives to pamidronate and zoledronic acid which may be more
      convenient for patients, and perhaps also cost-effective, should also be of
      ongoing interest.

PMID- 17559750
TI  - Validation of a questionnaire to assess niacin-induced cutaneous flushing.
AB  - BACKGROUND: Niacin is currently the most effective approved agent for raising
      high-density lipoprotein cholesterol. However, niacin-induced cutaneous flushing
      (redness, warmth, tingling and/or itching) significantly limits patient
      acceptance. To further characterize flushing, a patient-reported Flushing Symptom
      Questionnaire (FSQ) was developed and validated. METHODS: The FSQ was validated
      in an 8-week, randomized, double-blind, placebo-controlled trial of extended
      release (ER) niacin and placebo. The primary flushing endpoint of the study was
      based on the single Global Flushing Severity Score (GFSS), an item within the
      FSQ, which assesses overall flushing severity on a 0-10 discretized analog scale.
      RESULTS: A total of 175 patients were randomized to one of four treatment groups
      (sequences of placebo and ER niacin [given as niacin (NIASPAN) 1 g (N1) and 2g
      (N2)]. Test-retest reliability and reproducibility coefficients for the single
      item GFSS were all above 0.75. Construct validity was supported by moderate to
      strong correlations (r > 0.5) with other FSQ items. All FSQ item scores and
      specifically the GFSS discriminated between treatment groups and demonstrated
      expected relationships with predefined known groups. The GFSS demonstrated high
      responsiveness in patients who switched from ER niacin to placebo. The ability of
      the GFSS and GFBS to discriminate changes in flushing symptoms in patients who
      increased drug dose was less than expected possibly due to accommodation to the
      flushing effects of niacin over time; differential drop-out due to flushing;
      and/or FSQ items not being sensitive enough to detect a change that was present.
      CONCLUSIONS: The FSQ items and specifically the Global Flushing Severity Score
      (GFSS), are reliable and valid measures to assess niacin-induced flushing.

PMID- 17559751
TI  - Management of breakthrough seizures in the emergency department: continuity of
      patient care.
AB  - BACKGROUND: Epilepsy is a chronic disorder requiring long-term management.
      Communication between emergency physicians, neurologists, and primary care
      physicians (PCPs) is especially critical for the continuity of care for patients
      who present in an emergency department (ED) with a breakthrough seizure.
      Therefore, maximizing communication between the emergency physician and the PCP
      is of the utmost importance. The emergency physician, who is on the front line,
      must gather the information necessary to identify the underlying cause of the
      seizure and decide whether the pharmaceutical management must be changed. SCOPE:
      This paper provides a clinical commentary on issues to consider when managing
      breakthrough seizures in the ED, to inform and facilitate communication between
      emergency physicians, consulting neurologists, and PCPs. CONCLUSIONS: Clinical
      management decisions, especially when considering adjustment in an antiepileptic
      drug (AED) regimen, are often best made in coordination with a consulting
      neurologist. Increasing emergency physicians' comfort level regarding the use of
      newer-generation AEDs can improve the dialogue between the emergency physician
      and neurologist and the dialogue with the patient. Understanding the risks and
      benefits of the newer AEDs will assist the emergency physician in clinical
      decision making and, it is hoped, improve clinical outcomes. To preserve
      continuity of patient care, a patient's treating physician should be notified of
      all the particulars of the ED visit, and an appointment should be scheduled at
      the time of discharge for follow-up evaluation.

PMID- 17559752
TI  - Effects of ezetimibe on lipids and lipoproteins in patients with
      hypercholesterolemia and different apolipoprotein E genotypes.
AB  - BACKGROUND: The epsilon4 allele of the gene encoding apolipoprotein E (apoE) is
      associated with elevated serum levels of total cholesterol (TC) and low-density
      lipoprotein cholesterol (LDL-C), as well as an increased risk of coronary heart
      disease (CHD), greater disease severity, and higher CHD mortality. ApoE epsilon4
      allele carriers have also shown reduced lipid and lipoprotein responses to lipid
      modifying pharmacotherapy and lifestyle modifications. OBJECTIVE: To provide
      preliminary descriptive data on the effects of apoE genotype on lipid and
      lipoprotein responses to the cholesterol absorption inhibitor ezetimibe
      (Ezetrol/Zetia) in Hungarian subjects not at cholesterol goals at baseline.
      METHODS: This prospective open-label study compared the effects of the
      cholesterol absorption inhibitor ezetimibe 10 mg/day for up to 6 weeks added to
      existing therapies on the lipid profiles of 14 epsilon4 allele carriers and 14
      age- and gender-matched APOE3/APOE3 homozygotes. RESULTS: Treatment with
      ezetimibe reduced TC, LDL-, and triglycerides, and increased high-density
      lipoprotein cholesterol (HDL-) significantly from baseline, and to similar
      extents, in both groups, lowering TC from baseline by 13.7% in APOE3/APOE3
      homozygotes compared with 12.1% in epsilon4 allele carriers (p = 0.139); LDL-C by
      22.8% (vs. 19.6%; p = 0.081); and triglycerides by 9.2% (vs. 9.1%; p = 0.120).
      Ezetimibe also increased HDL-C by 8.0% in subjects with the epsilon3/epsilon3
      genotype compared with 8.9% in epsilon4 allele carriers (p = 0.263). CONCLUSIONS:
      Ezetimibe significantly improved lipid and lipoprotein profiles from baseline
      irrespective of apoE epsilon3/epsilon3 or epsilon4 genotype in Hungarian subjects
      not at cholesterol goals. Limitations of our study include its open-label nature
      and small sample population, as well as the facts that patients with the epsilon4
      allele were not included and data were not collected on initial cholesterol
      levels, initial statin doses, cholesterol responses to statins, and the safety
      and tolerability of ezetimibe. Further randomized controlled studies in larger
      numbers of people followed for longer intervals are warranted to confirm these
      findings.

PMID- 17559753
TI  - Single- and multiple-dose bioequivalence of two once-daily tramadol formulations
      using stereospecific analysis of tramadol and its demethylated (M1 and M5)
      metabolites.
AB  - OBJECTIVE: To assess bioequivalence of two once-daily formulations of tramadol
      (T) as well as delineate pharmacokinetics of its enantiomers and those of its
      main metabolites after single- and multiple-dose administration. METHODS: Single-
      and multiple-dose studies were conducted separately each in 48 healthy volunteers
      using an open-label, randomized, crossover design. Subjects received the 200 mg
      test (Tramadolor) and reference (Ultram ER) formulations in a randomized manner
      separated by a 7-day washout period once (single-dose study) or once daily for 7
      days (multiple-dose study). Blood was sampled on days 1-2 (single-dose) or days 4
      7 (multiple-dose), and plasma samples were analyzed using a stereospecific assay
      for quantitation of individual enantiomers of T and its active O-demethylated
      (M1) and N,O-demethylated (M5) metabolites. Bioequivalence was assessed using log
      transformation and 90% confidence intervals. RESULTS: All analytes showed
      stereoselectivity after single and multiple doses of both products, with average
      concentrations of (+)-T, (-)-M1, and (-)-M5 exceeding those of their respective
      antipode. However, a decrease in steady-state oral clearance of T relative to
      single dose was not stereoselective. In both studies, the formulations were
      bioequivalent with regard to AUG and Cmax for both enantiomers of all analytes.
      The Tmax for the reference (10-12 h) was significantly (p < 0.05) longer than
      that for the test (5-6 h). Degree of fluctuation of T enantiomers after the test
      was greater than the reference. Both formulations were tolerated relatively well.
      CONCLUSIONS: Tramadolor and Ultram ER were bioequivalent for both enantiomers of
      T, M1 and M5. It is unlikely there would be any significant clinical differences
      between the two formulations.

PMID- 17559754
TI  - Pain relief and pain-related sleep disturbance with extended-release tramadol in
      patients with osteoarthritis.
AB  - OBJECTIVE: This analysis evaluated changes in pain and pain-related sleep
      disturbance with extended-release tramadol (tramadol ER) in patients with
      moderate, chronic osteoarthritis pain, and the influence of pain reduction on
      pain-related sleep disturbance. METHODS: Data were obtained from a 12-week,
      randomized, double-blind, placebo-controlled, fixed-dose study of tramadol ER 100
      mg, 200 mg, 300 mg, or 400 mg once daily. Subjects reported osteoarthritis pain
      intensity with a 100-mm visual analog scale (VAS; 0 = no pain, 100 = extreme
      pain). A Sleep Problems Index score from 0 to 100 mm (0 = never, 100 = always)
      was determined from the mean of three subject-reported scores of pain-related
      sleep disturbance. RESULTS: A total of 815 subjects received tramadol ER (all
      doses combined) and 205 received placebo. Mean pain reduction at 12 weeks was 
      30.4 mm and -21.5 mm for tramadol ER and placebo, respectively (p < 0.001).
      Tramadol ER-treated subjects were nearly twice as likely as placebo subjects to
      have clinically meaningful pain reduction at 12 weeks, defined as 30 mm or
      greater reduction (odds ratio [OR] = 1.84, P < 0.001) or 30% or greater reduction
      (OR = 1.95, P < 0.001) in pain. Clinically meaningful reduction of pain-related
      sleep disturbance at 12 weeks, defined as 16 mm or greater improvement on the
      Sleep Problems Index, was more common for tramadol ER than placebo (51% vs. 42%,
      respectively, p = 0.022). Pain reduction was associated with reduced pain-related
      sleep disturbance (R = 0.51). Study treatment was generally well tolerated.
      Possible limitations included homogeneity of pain scores at baseline and the
      effect of adverse events on sleep analyses. CONCLUSIONS: In patients with chronic
      osteoarthritis pain, pain reduction is associated with decreased pain-related
      sleep disturbance.

PMID- 17559755
TI  - A comparative study of the efficacy of acute and continuation treatment with
      escitalopram versus duloxetine in patients with major depressive disorder.
AB  - OBJECTIVE: This study evaluated the efficacy and tolerability of escitalopram and
      duloxetine in the treatment of major depressive disorder (MDD). RESEARCH DESIGN
      AND METHODS: Patients were randomised to 24 weeks of double-blind treatment with
      fixed doses of escitalopram (20 mg) (n = 143) or duloxetine (60 mg) (n = 151).
      The primary analysis of efficacy was an analysis of covariance (ANCOVA) of change
      from baseline to endpoint (week 24) in MADRS total score (last observation
      carried forward). MAIN OUTCOME MEASURES; RESULTS: At week 8, the mean change from
      baseline in total MADRS score was -19.5 for patients treated with escitalopram (n
      = 141) and -17.4 for patients treated with duloxetine (n = 146), a difference of
      2.1 points (p < 0.05). At week 8, the proportion of responders (> or = 50%
      decrease in MADRS) was 69% (escitalopram) and 58% (duloxetine) (p < 0.05) and
      remission (MADRS < or = 12) rates were 56% (escitalopram) and 48% (duloxetine)
      (NS). For the primary endpoint, the mean change from baseline in total MADRS
      score at week 24 was -23.4 for patients treated with escitalopram and -21.7 for
      patients treated with duloxetine, a difference of 1.7 points (p = 0.055, one
      sided). The difference in mean change from baseline in MADRS total score favoured
      escitalopram at weeks 1, 2, 4, 8, 12 and 16 (p < 0.05). The overall withdrawal
      rates were 22% (escitalopram) and 25% (duloxetine) (NS). The withdrawal rate due
      to adverse events was lower for escitalopram (9%) compared to duloxetine (17%) (p
      < 0.05) and significantly more patients treated with duloxetine reported insomnia
      (12.6% vs. 4.9%) and constipation (8.6% vs. 2.8%). CONCLUSION: Escitalopram was
      superior to duloxetine in acute treatment and at least as efficacious and better
      tolerated in long-term treatment of MDD.

PMID- 17559756
TI  - The Barthel Index and modified Rankin Scale as prognostic tools for long-term
      outcomes after stroke: a qualitative review of the literature.
AB  - OBJECTIVE: Providing a quantitative prognosis after a stroke is important to
      clinicians and patients as well as to researchers interested in projecting the
      results of clinical trials and other studies. Thus, we critically reviewed the
      evidence supporting the prognostic value of two frequently-used measures, the
      Barthel Index (BI) and modified Rankin Scale (mRS) for long-term outcomes.
      METHODS: A narrative review of the peer-reviewed medical literature obtained by
      searching Medline 1966 to January 2004--using the phrase '[stroke] AND [Barthel
      OR Rankin]'--was conducted to assess the strength of the evidence for these
      measures and answer three main questions: How good are the BI and mRS at
      predicting (1) the level of care required, (2) the time-course of recovery, and
      (3) mortality. Abstracts were screened for the presence of actual data on the
      prognostic impact of BI and mRS on these endpoints, and selected articles were
      fully reviewed and abstracted. Additional articles were identified from
      bibliographies of the retrieved papers. RESULTS: Of 753 abstracts screened, 89
      articles were selected for detailed assessment. Early disability and global
      outcome (< or = 7 days) were shown in 21 studies to be strong predictors of care
      needs. This relation appears to be mainly biological, not country-specific.
      Recovery was shown in 18 studies to be strongly related to early BI. In contrast,
      the 11 studies examining mortality provided insufficient information to directly
      support the prognostic value of either measure. Key limitations of this review
      include heterogeneity of available studies (e.g., time-points, outcome,
      parameterization) and relative lack of information on the mRS. CONCLUSIONS:
      Despite the lack of uniformity in existing studies, the evidence overall is quite
      strong, supporting the use of BI and mRS as prognostic tools. External non
      treatment modifiable factors which also determine long-term outcome (e.g., social
      support) have to be taken into account.

PMID- 17559757
TI  - Patient acceptance of a novel electronic auto-injector device to administer
      recombinant human growth hormone: results from an open-label, user survey of
      everyday use.
AB  - OBJECTIVE: To measure the user acceptance of a electronic auto-injector device
      (easypod) for recombinant human growth hormone (r-hGH) administration. STUDY
      DESIGN AND METHODS: This was an open-label, uncontrolled study in which
      participants (n = 61) were trained to use the device to administer subcutaneous
      recombinant human growth hormone (r-hGH). Participants' opinions on the device
      were recorded by questionnaire and/or telephone interview during training and
      after 15 and 60 days of use. Opinions on the device were also collected from
      nurses or physicians who trained the participants in device use. RESULTS: After
      60 days, 98% (54/55) of responders reported a 'good' or 'very good' overall
      impression of the device. The pre-programmed dose feature, skin sensor, on-screen
      instructions, display of remaining dose, confirmation of injected dose and
      automatic needle attachment were identified by the majority of participants as
      'very useful'. Participants were reported to have easily understood the injection
      process, and 87% (48/55) expressed a preference to continue use of the device.
      The device had a good safety profile, and no adverse events were reported during
      the study or follow-up periods. CONCLUSIONS: Participants had a good overall
      impression of the device and the majority expressed a preference to continue its
      use. The combination of features offered by the device make it user-friendly, and
      such ease of use may facilitate greater adherence to treatment, in turn improving
      therapy outcomes.

PMID- 17559758
TI  - Cost-utility of levonorgestrel intrauterine system compared with hysterectomy and
      second generation endometrial ablative techniques in managing patients with
      menorrhagia in the UK.
AB  - OBJECTIVE: To estimate the cost-utility of levonorgestrel intrauterine system
      (LNG-IUS; Mirena) compared to second generation endometrial ablative techniques
      [i.e. microwave endometrial ablation (MEA) and thermal balloon endometrial
      ablation (TBEA)) and hysterectomy in the UK. METHODS: Clinical and utility data
      from a 5-year randomised controlled trial comparing LNG-IUS with hysterectomy
      were combined with further data from published studies to construct a state
      transition (Markov) model. The model depicted the movement of patients between
      health states over 5 years following treatment for menorrhagia. The model was
      used to estimate the cost-utility of LNG-IUS followed by ablation (L-A); LNG-IUS
      followed by hysterectomy (L-H); immediate ablation (MEA or TBEA) and immediate
      hysterectomy in the UK at 2004/2005 prices, from the perspective of the UK's
      National Health Service (NHS). MAIN OUTCOME MEASURES AND RESULTS: The expected 5
      yearly cost of treating menorrhagia with L-A, L-H, TBEA, MEA and hysterectomy was
      estimated to be 828 pounds sterling, 1355 pounds sterling, 1679 pounds sterling,
      1812 pounds sterling and 2983 pounds sterling per patient respectively and the
      expected level of health gain to be 4.14, 4.12, 4.13, 4.13 and 4.01 QALYs per
      patient respectively. LNG-IUS followed by ablation dominated all the alternative
      treatments. Hysterectomy was dominated by the alternative treatments. Sensitivity
      analysis found the model to be sensitive to the quality of life data used.
      CONCLUSION: Within the model's limitations, LNGIUS followed by ablation appears
      to offer the NHS a cost-effective treatment for menorrhagia, when compared to
      immediate surgery, affording the NHS a less expensive treatment modality without
      detrimental effects on resulting health gain.

PMID- 17559759
TI  - Scarf versus chevron osteotomy in hallux valgus: a randomized controlled trial in
      96 patients.
AB  - BACKGROUND: The degree of correction of hallux valgus deformity using a distal
      chevron osteotomy is reported as limited. The scarf osteotomy is reported to
      correct large intermetatarsal angles (IMA). The purpose of this study was to
      evaluate if one technique gave greater correction of the IMA and hallux valgus
      angle (HVA) than the other. METHODS: After informed consent, 96 feet in 83
      patients were randomized into two treatment groups (49 scarf and 47 chevron
      osteotomies). The results were evaluated using the American Orthopaedic Foot and
      Ankle Society (AOFAS) Hallux Valgus Scale and radiographic HVA and IMA
      measurements. RESULTS: At 27 (range 23-31) months followup both groups improved.
      The AOFAS score in the chevron group improved from 48 to 89 points and in the
      scarf group from 47 to 91 points. In the chevron group the HVA corrected from 30
      to 17 degrees, and in the scarf group the HVA corrected from 29 to 18 degrees. In
      both groups, the IMA was corrected from 13 to 10 degrees. The differences were
      not statistically significant. Three patients in the chevron group developed a
      partial metatarsal head necrosis. In the scarf group, four patients developed
      grade 1 complex regional pain syndrome compared to one patient in the chevron
      group. CONCLUSIONS: No differences of statistical significance could be measured
      between the two groups with respect to the AOFAS score, HVA, and IMA. Although
      both groups showed good to excellent results, we favor the chevron osteotomy
      because the procedure is technically less demanding.

PMID- 17559760
TI  - Supramalleolar lateral closing wedge osteotomy for the treatment of varus ankle
      arthrosis.
AB  - BACKGROUND: Medial ankle joint pain with localized cartilage degeneration due to
      medial joint overload in varus malalignment of the hindfoot lends itself to
      treatment by lateral closing wedge supramalleolar osteotomy. METHODS: From 1998
      to 2003, nine patients between the ages of 21 to 59 years were operated. The
      etiology of the malalignment and degeneration was posttraumatic in eight and
      childhood osteomyelitis in one. Preoperative and postoperative standing
      radiographs were analyzed to determine the correction of the deformity and the
      grade of degeneration. Function and pain were assessed using the American
      Orthopaedic Foot and Ankle Society (AOFAS) Ankle-Hindfoot Scale. The average
      followup was 56 (range 15 to 88) months. RESULTS: The average time to osseous
      union was 10 +/- 3.31 weeks. There were no operative or postoperative
      complications. The average AOFAS score improved from 48 +/- 16.0 preoperatively
      to 74 +/- 11.7 postoperatively (p<0.004). The average pain subscore improved from
      16 +/- 8.8 to 30 +/- 7.1 (p<0.008). The average tibial-ankle surface angle
      improved from 6.9 +/- 3.8 degrees of varus preoperatively to 0.6 +/- 1.9 degrees
      of valgus postoperatively (p<0.004). In the sagittal plane, the tibial-lateral
      surface angle remained unchanged. At the final followup, two patients showed
      progression of radiographic ankle arthrosis grades. In one patient, it rose from
      grade 0 to I. In the other patient it advanced from grade II to III, with
      subsequent ankle arthrodesis required 16 months after the index procedure. Seven
      patients returned to their previous work. CONCLUSIONS: Lateral supramalleolar
      closing wedge osteotomy was an easy and safe procedure, effectively correcting
      hindfoot malalignment, relieving pain, restoring function, and halting
      progression of the degeneration in the short-term to mid-term in seven of nine
      patients.

PMID- 17559761
TI  - Results of endoscopic plantar fascia release.
AB  - BACKGROUND: Conservative treatment for plantar fasciitis usually provides
      improvement, but some patients progress to surgery. Open release is most commonly
      performed but is associated with prolonged recovery and complications. Endoscopic
      plantar fascia release (EPFR) has become popular recently. We present our
      results. METHODS: Twenty patients (23 feet) had EPFR. Sixteen patients (19 feet)
      were available for followup after at least 1 year. Ten were women and 6 were men,
      with an average age of 44.7 (range 28 to 70) years. The average followup was 47
      months. The American Orthopaedic Foot and Ankle Society (AOFAS) Ankle-Hindfoot
      Scale and Maryland Foot Score were used for evaluation. Gender, obesity,
      severity, length of preoperative symptoms, and workers compensation (WC) status
      were studied. RESULTS: The average AOFAS and Maryland scores improved
      postoperatively (66 to 88, p<0.05; 62 to 83, p<0.05, respectively). Women
      improved 25 (AOFAS) and 23 points (Maryland) points. Men improved 16 (AOFAS) and
      17 points (Maryland) points. Obese patients improved 38 and 28 points,
      respectively. Normal weight patients improved 16 and 19 points, respectively.
      Postoperative scores for patients with high preoperative severity improved from
      58 to 81 (AOFAS) and from 52 to 73 (Maryland). Patients with moderate
      preoperative severity achieved scores from 72 to 93 and from 70 to 91. Patients
      who had symptoms longer than 2 years before EPFR had lower postoperative scores.
      Non-WC patients improved 25 (AOFAS) and 24 (Maryland) points. WC patients
      improved 18 and 16 points, respectively. CONCLUSIONS: EPFR provides significantly
      improved patient outcomes. Patients with more severe symptoms before EPFR and
      those with symptoms for longer than 2 years had worse results. Obesity had no
      negative effect on outcome. WC patients had inferior results compared to non-WC
      patients. Women achieved better results than men. This finding may be biased
      because most WC patients were men.

PMID- 17559762
TI  - Correction of severe recurrent clubfoot using a simplified setting of the
      Ilizarov device.
AB  - BACKGROUND: Severe recurrent clubfoot deformities are challenging to treat. The
      Ilizarov method offers a safer alternative; however, the management of the device
      is complex. METHODS: A simplified standard setting of the Ilizarov device was
      used to treat 29 patients (35 feet) with a mean age of 14 years with severely
      stiff recurrent clubfoot deformities and large scars caused by one or more
      previous surgeries. This simplification involved a correction in two stages:
      first a gradual correction of the equinus, varus, cavus, and adduction
      deformities and later an acute correction of the supination deformity. All feet
      underwent percutaneous Achilles tenotomy and plantar fasciotomy; 11 feet required
      an additional midfoot osteotomy. The final outcome was scored as good (complete
      correction and no pain); fair (partial correction with plantigrade foot and
      occasional pain); or poor (nonplantigrade foot and continuous pain during
      walking). RESULTS: After a mean followup of 56 months, the results were good in
      27 feet (77%), fair in five feet (14%), and poor in three feet (9%). Early
      complications were complete dislocation of the first metatarsophalangeal joint in
      two feet and partial dislocation of the distal tibial epiphysis in two feet. Late
      complications were recurrence of the deformity (11 feet), spontaneous ankylosis
      (16 feet), and symptomatic foot and ankle arthritis (7 feet). Arthrodesis was
      performed in 13 feet at an average of 21 months after the index surgery to treat
      symptomatic arthritis or correct disabling residual deformities. CONCLUSIONS: The
      Ilizarov device allowed correction of all the complex deformities of severe
      recurrent clubfoot with minimal operative intervention. Complications were
      numerous but manageable and for the most part did not compromise overall patient
      satisfaction in this very difficult to treat clinical condition.

PMID- 17559763
TI  - Treatment of severe, painful pes planovalgus deformity with hindfoot arthrodesis
      and wedge-shaped tricortical allograft.
AB  - BACKGROUND: This study tested the hypothesis that modification of the standard
      technique of hindfoot arthrodesis with the use of a wedge-shaped tricortical
      allograft would improve the amount of correction of pes planovalgus deformity.
      The results were compared to previous reports. METHODS: Between 1998 and 2005,
      the senior author (LBC) performed 13 hindfoot arthrodeses on 12 patients using an
      allograft to improve correction of the deformity for severe, painful pes
      planovalgus deformity. The average patient age was 55 (range 27 to 77) years.
      There were seven women and five men. The indications were posterior tibial tendon
      dysfunction (seven feet), rheumatoid arthritis (three feet), post-traumatic
      arthritis and deformity (one foot), congenital pes planovalgus (one foot), and
      tarsal coalition (one foot). RESULTS: Twelve of 13 feet achieved union by 12
      weeks postoperatively. There was one nonunion. The average time to fusion was 12
      weeks. All 12 patients were satisfied with the results of the operation. The
      average postoperative American Orthopaedic Foot and Ankle Society (AOFAS) Ankle
      Hindfoot score was 87 points, and the AOFAS Midfoot score was 85 points.
      Preoperative and postoperative radiographs were compared to evaluate correction
      of deformity. On lateral weightbearing views, the talo-first metatarsal angle
      improved from 15 to 6 degrees, and the lateral talocalcaneal angle improved from
      48 to 35 degrees. On anteroposterior views, the talo-first metatarsal angle
      improved from 17 to 7 degrees, the talonavicular coverage decreased from 28 to 13
      degrees, and the talocalcaneal angle improved from 23 to 13 degrees. CONCLUSIONS:
      A simple modification of the addition of allograft to a common procedure of
      hindfoot arthrodesis to treat severe, painful pes planovalgus results is reliable
      and offers satisfactory correction.

PMID- 17559764
TI  - Walking and running plantar pressure analysis before and after resection of
      tarsal coalition.
AB  - BACKGROUND: Conservative treatment failure in symptomatic tarsal coalition
      usually mandates bar resection as a preferred operative alternative. The outcome
      of this procedure generally has been assessed by clinical measures. The purpose
      of our study was to evaluate whether plantar pressure distribution is normalized
      after bar resection. METHODS: This study compared three groups: nine candidates
      for resection of tarsal coalition, nine patients between 2 and 4 years after bar
      resection (not the same patients who were candidates for resection), and nine
      control subjects. The ankle and hindfoot were evaluated according to the American
      Orthopaedic Foot and Ankle Society Ankle-Hindfoot Scale. Mean plantar pressure
      and mean normalized impulses were calculated during walking and running. RESULTS:
      Significantly higher AOFAS scores were demonstrated in the postoperative group
      compared with the preoperative group (p<0.01). Medial midfoot pressures
      demonstrated the most consistent differences between groups. Preoperative feet
      had significantly higher medial midfoot pressures compared with the control group
      both during walking and running. Feet that had resection did not demonstrate
      significantly higher medial midfoot pressures during walking compared with the
      control group. However, during running, this segment's pressures were
      significantly higher both in preoperative (p=0.000) and in postoperative
      (p=0.023) feet compared with the control group. Heel segments revealed decreased
      pressures laterally both in preoperative feet and in postoperative feet compared
      with the control group. CONCLUSIONS: Running demonstrates that normal plantar
      pressures are not recreated after resection of tarsal coalition. However, close
      to normal walking pressure distribution is consistent with the favorable clinical
      outcome observed in most patients after bar resection. CLINICAL RELEVANCE:
      Regaining full recreational activity after resection of a tarsal coalition, i.e.
      running, may have implications on abnormal foot loading and torque, thus
      promoting degenerative changes in the subtalar and adjacent joints.

PMID- 17559765
TI  - Avulsion fractures of the fifth metatarsal base: a prospective outcome study.
AB  - BACKGROUND: This prospective study was done to evaluate functional outcomes after
      acute avulsion fractures of the fifth metatarsal base. METHODS: Fifty-two
      patients who sustained an avulsion fracture of the fifth metatarsal base and
      presented to the outpatient clinic of our hospital system were treated according
      to a standardized protocol. A total of 49 patients (50 fractures) were available
      for 1-year followup. There were eight men and 41 women with an average age of
      41.9 (range 17 to 81) years. The lower extremity was placed in a hard-soled shoe,
      and patients were allowed to bear weight as tolerated. Baseline data collection
      consisted of demographic information, and radiographic, and functional
      evaluation. Patients were seen at regularly scheduled visits for 6 months and
      then contacted at 1 year to obtain followup information. A Short Musculoskeletal
      Function Assessment (SMFA) questionnaire was obtained at 6 months and 1 year.
      Analyses were performed to determine differences in outcome based on demographics
      and injury information. A p value of less than 0.05 was considered significant.
      RESULTS: An average of 22 days were lost from work, with 23 patients (46.9%)
      taking up to 10 days, 18 (36.7%) taking 10 days or longer off work, and eight
      patients (16.4%) losing no days of work. Based on self-reports, 10 patients
      (20.4%) had returned to pre-injury functional status by 3 months, 42 patients
      (85.7%) by 6 months, and all 49 patients by 1 year. At six and 12 months, no
      differences in SFMA were found based on gender, fracture type, or amount of
      fracture displacement. CONCLUSIONS: Fracture of the fifth metatarsal base often
      is a source of lost work productivity. Although patients can be expected to
      return to their preinjury level of function, recovery may take 6 months or
      longer.

PMID- 17559766
TI  - The compartments of the foot: a 3-tesla magnetic resonance imaging study with
      clinical correlates for needle pressure testing.
AB  - BACKGROUND: Reliable measurement of subfascial pressures represents an essential
      part of compartment syndrome management. To date, there is neither consensus on
      the number or location of foot compartments, nor a standardized protocol for
      needle placement. The purpose of this study was to devise a new system using 3
      Tesla MRI that assesses the number and location of these compartments. METHODS:
      To document the specific location of foot compartments, high resolution 3-Tesla
      MRI (General Electric, Milwaukee, WI) was coupled with a dedicated transmit
      receive high signal-to-noise foot/ankle coil (IGC-Medical Advances, Milwaukee,
      WI). Individual compartments were highlighted and mapped to T1-weighted MRI.
      Three-dimensional image analysis allowed standardized needle placement
      recommendations. RESULTS: Six feet from healthy volunteers were imaged. From
      these, ten compartments were described: (1) medial, (2) central superficial, (3)
      central deep (adductor), (4) lateral, (5-8) interossei, (9) calcaneal, and (10)
      skin. Optimal needle placement and depth were identified. CONCLUSIONS: The
      proposed system allowed us to assess the number and location of foot
      compartments. Computer image analysis enabled us to define exact points for
      needle insertion and depth of penetration for accurate pressure monitoring.

PMID- 17559767
TI  - Two distinctive subungual pathologies: subungual exostosis and subungual
      osteochondroma.
AB  - BACKGROUND: The purpose of this study was to present features that differentiate
      subungual exostosis from subungual osteochondroma. METHODS: We treated 11
      patients for subungual masses. All were confirmed by radiographic and histologic
      evaluations to be subungual exostosis or subungual osteochondroma. The study
      patients comprised eight female and three male patients with a mean age at
      presentation of 18.7 years (range 1.5 to 70.9). In the five patients with
      subungual exostosis, three (60%) had a toe lesion, and two (40%) had a finger
      lesion. In the six patients with subungual osteochondroma, four (67%) had a toe
      lesion, and two (33%) had finger lesions. We analyzed the clinical features,
      including trauma history, the existence of infection before surgery, tumor
      recurrence, and postoperative nail deformity. RESULTS: In all patients, the
      lesions presented as an exophytic tumor of the nail apparatus, beneath the nail
      plate, which varied in size from 0.6 x 0.4 cm to 1.2 x 0.9 cm. Excision of these
      masses produced useful toes or fingers without pain, a tender scar, or nail
      deformity. Although nails were deformed preoperatively, they grew back without
      ridges or cracks within 3 to 5 months postoperatively. There were no recurrences
      based on clinical and radiographic evaluations, and both tumor types showed
      characteristic radiographic and histologic differences. CONCLUSIONS: Subungual
      exostosis and subungual osteochondroma are benign but have distinct osseous
      pathologies. We concluded that subungual exostosis is clinically,
      developmentally, radiographically, and histologically distinct from subungual
      osteochondroma.

PMID- 17559768
TI  - Biomechanical comparison of the interosseous tibiofibular ligament and the
      anterior tibiofibular ligament.
AB  - BACKGROUND: The mechanical importance of the interosseous tibiofibular ligament
      of the ankle is unclear. The purpose of the current study was to compare the
      stiffness and strength of the interosseous tibiofibular ligament to that of the
      anterior tibiofibular ligament. METHODS: Twelve pairs of ankles were obtained
      from the Maryland State Anatomy Board. All soft tissue was removed except for the
      interosseous tibiofibular ligament in one ankle of each pair and the anterior
      tibiofibular ligament in the contralateral ankle. The assignment of which
      ligament would be excised in the right or left ankle of each pair was random. The
      specimens were potted as bone-ligament-bone preparations and mounted in a
      servohydraulic testing machine so that the ligament's long axis was coincident
      with the actuator. Specimens were elongated at 0.5 mm/s until rupture. Failure
      load and failure site were recorded, and stiffness was calculated. Stiffness and
      failure loads were compared with a paired t-test. Significance was set at p <
      0.05. RESULTS: The interosseous ligament was significantly stiffer (234 +/- 122
      N/mm) than the anterior tibiofibular ligament (162 +/- 64 N/mm). The mean failure
      load of the interosseous tibiofibular ligament (822 +/- 298 N) was significantly
      greater than that of the anterior tibiofibular ligament (625 +/- 255 N).
      CONCLUSIONS: The interosseous tibiofibular ligament is stiffer and stronger than
      the anterior tibiofibular ligament. CLINICAL RELEVANCE. The current study
      suggests that the interosseous ligament plays an important role in the stability
      of the ankle, and its status should be part of the diagnostic evaluation in
      syndesmotic instability.

PMID- 17559769
TI  - Comparison of two intramedullary nails for tibiotalocalcaneal fusion: anatomic
      and radiographic considerations.
AB  - BACKGROUND: Retrograde intramedullary nailing is an established procedure for
      tibiotalocalcaneal arthrodesis. This study was conducted to see whether, and if
      so to what extent, nail design modifications would influence the risk to anatomic
      structures and the bony coverage of the nail base. METHODS: Six pairs of thawed
      fresh-frozen cadaver legs received two different intramedullary nails (N1:
      straight nail, lateral-medial tip locking; N2: valgus-curved nail, medial-lateral
      tip locking) under simulated operative conditions. The specimens were dissected;
      distances between the at-risk structures and the hardware were measured. The
      hindfoot axis and the volume of the intracalcaneal nail portion were determined
      with CT. RESULTS: At the plantar entry site, N2 was significantly farther from
      the flexor hallucis longus tendon (p=0.047), the medial plantar artery (p=0.026),
      and the lateral plantar nerve (p=0.026) than N1. The lateral-medial calcaneal
      locking screw of N1 damaged significantly more often the peroneus brevis tendon
      (p=0.03) than N2. The proximal tip-locking screw, N2, was significantly farther
      from the anterior tibial artery (p=0.075) and the deep (p=0.047) and superficial
      peroneal nerves (p=0.009) than N1; N1 was significantly farther from the great
      saphenous vein (p=0.075) than N2. The distal tip-locking screw, N1. damaged
      significantly more often the extensor digitorum longus (p=0.007), the anterior
      tibial artery(p = 0.04), and the deep and superficial peroneal nerves (p=0.03)
      than N2. CT did not show any significant changes in the hindfoot axis with either
      device; intracalcaneal nail volumes were similar. CONCLUSIONS: A curved nail can
      increase the distance to at-risk plantar structures. Medial-lateral nail-tip
      locking appears to have less risk to neurovascular structures. CLINICAL
      RELEVANCE: Safer retrograde intramedullary nailing for tibiotalocalcaneal fusion
      requires knowledge of the structures at risk and appropriate operative technique.

PMID- 17559770
TI  - Risk to neurovascular structures using posterolateral percutaneous ankle screw
      placement: a cadaver study.
AB  - BACKGROUND: Over the past 20 years, ankle arthrodesis with use of screw
      augmentation has become a popular technique to gain fusion of the arthritic
      ankle. The objective of this cadaver study was to identify the risks to local
      neurovascular structures using standard operative practices for percutaneous
      guide pin placement. METHODS: Nine fresh frozen cadaver limbs were used. A guide
      pin from the Synthes (Paoli, PA) 7.3-mm cannulated set was placed percutaneously
      into the distal posterolateral leg with the ankle held in neutral position. A
      layered dissection was then performed from the skin to tibia. Neurovascular
      injury and distance of the guide pin from the sural and tibial nerves were noted.
      RESULTS: The guide pin did not touch the sural or tibial nerves in any specimens.
      With this technique, the mean distance of the pin from the sural nerve and tibial
      nerve at the closest point was 0.9 mm and 6.5 mm, respectively. CONCLUSIONS: In
      placement of a percutaneous screw, care should be taken to start the
      posterolateral guide pin placement more lateral or closer to the fibula at this
      level in the leg to avoid injury to the sural nerve. Additionally, the tibial
      nerve is potentially an at risk structure if percutaneous pin insertion crosses
      medial to the coronal plane midline. CLINICAL RELEVANCE: The use of percutaneous
      screw placement is safe and effective with minimal risk to local neurovascular
      structures if standard operative technique is followed.

PMID- 17559771
TI  - Influence of the abductor hallucis muscle on the medial arch of the foot: a
      kinematic and anatomical cadaver study.
AB  - BACKGROUND: Most studies of degenerative flatfoot have focused on the posterior
      tibial muscle, an extrinsic muscle of the foot. However, there is evidence that
      the intrinsic muscles, in particular the abductor hallucis (ABH), are active
      during late stance and toe-off phases of gait. The purpose of this study was to
      analyze the kinematic effect of a simulated contraction of the abductor hallucis
      muscle on a cadaver lower limb specimen. METHODS: Eight below-knee cadaver
      specimens were prepared. The abductor hallucis muscle was exposed and the entire
      muscle-tendon unit excised. A suture secured to the calcaneal origin of the
      muscle and tendon was passed through a pulley at the ABH sesamoid attachment. The
      specimen was mounted on an experimental rig in a 'standing' position. Motions in
      the first metatarsal, tibia, and calcaneus were tracked using the 'Flock of
      Birds' motion analysis system (Ascension Technology, Burlington, VT). Muscle
      contraction was simulated by applying tension on the suture. RESULTS: All eight
      specimens showed an origin from the posteromedial calcaneus and an insertion at
      the tibial sesamoid. All specimens also demonstrated a fascial sling in the
      hindfoot, lifting the abductor hallucis muscle to give it an inverted 'V' shaped
      configuration. Simulated contraction of the abductor hallucis muscle caused
      flexion and supination of the first metatarsal, inversion of the calcaneus, and
      external rotation of the tibia, consistent with elevation of the arch.
      CONCLUSIONS AND CLINICAL RELEVANCE: The abductor hallucis muscle acts as a
      dynamic elevator of the arch. Understanding this mechanism may change the way we
      understand and treat pes planus, posterior tibial tendon dysfunction, hallux
      valgus, and Charcot neuroarthropathy.

PMID- 17559772
TI  - Ganglion cysts of the midfoot presenting as bilateral accessory tarsal navicular
      bones in a child: a case report.

PMID- 17559773
TI  - Painful os talus secundarius: a case report and imaging findings.

PMID- 17559774
TI  - Conservative treatment of subtalar osteochondritis dissecans: a case report.

PMID- 17559775
TI  - Adult-onset lower extremity focal dystonia: case reports.

PMID- 17559776
TI  - Vascularized iliac crest bone graft for talar defects: case reports.

PMID- 17559777
TI  - Technique tip: easing subatmospheric wound dressing application and increasing
      sponge conformity.

PMID- 17559778
TI  - Clinical tip: a new clinical sign associated with metatarsophalangeal joint
      synovitis of the lesser toes.

PMID- 17559779
TI  - Technique tip: dorsal wedge resection (uniplanar) in the chevron osteotomy for
      high distal metatarsal articular angle bunions.

PMID- 17559780
TI  - Technique tip: temporary tibiotalar pinning to facilitate hindfoot arthrodesis.

PMID- 17559781
TI  - Special report: highlights of the 22nd Annual Summer Meeting of the American
      Orthopaedic Foot and Ankle Society, La Jolla,California, July 14-16, 2006.

PMID- 17559782
TI  - Current concepts review: hallux valgus part 1: pathomechanics, clinical
      assessment, and nonoperative management.

PMID- 17559783
TI  - Re: Etiologic factors associated with symptomatic Achilles tendinopathy.

PMID- 17559784
TI  - Optimisation of calculation methods for determination of surface tensions by drop
      profile analysis tensiometry.
AB  - The standard technique for measuring surface or interfacial tension by drop
      profile analysis requires two main steps: (i) acquisition of drop/bubble images
      and determination of the profile coordinates via edge detection techniques; (ii)
      fitting of the theoretical drop/bubble profile to the experimental coordinates
      using the interfacial tension gamma as adjustable parameter. As to edge detection
      technique, usually the position of the maximum grey level gradient is assumed to
      be the drop edge. In order to increase the accuracy of edge detection the
      procedure of fitting a normal distribution function to the experimental grey
      level gradients yields accurate results when the drop edge is located into the
      distribution centre. Conventional algorithms use the arc length along the drop
      profile as independent variable and fit in a vertical, horizontal or normal
      direction to the experimental shape coordinates, requiring that the coordinates
      have to be interpolated between experimental points. For small drops having an
      almost spherical shape, this technique leads to rather large errors. To avoid
      this interpolation problem a transformation of the Gauss-Laplace equation into
      polar coordinates can provide higher accuracy. For this, the angle of rotation is
      used as independent variable and the origin of the coordinate system is located
      exactly between the drop apex and the capillary tip at which the drop or bubble
      is formed.

PMID- 17559785
TI  - Surface rheology, equilibrium and dynamic features at interfaces, with emphasis
      on efficient tools for probing polymer dynamics at interfaces.
AB  - Adequately probing interfacial or (free) surface waves offers the possibility of
      exploring qualitative and quantitative equilibrium and rheological features hence
      large scale and long time dynamics. Several experimental techniques are briefly
      reviewed. The combination of capillary waves experiments with methods based on
      analyzing the mechanical deformation of the surface allows to explore dynamics
      from the microsecond scale up to collective phenomena relaxing at very long
      times, seconds, minutes or even hours. Results related to the scaling behavior of
      insoluble polymer films, and to the existence of a glass transition in quasi-2D
      systems are also discussed.

PMID- 17559786
TI  - Electro-convective versus electroosmotic instability in concentration
      polarization.
AB  - Electro-convection is reviewed as a mechanism of mixing in the diffusion layer of
      a strong electrolyte adjacent to a charge-selective solid, such as an ion
      exchange (electrodialysis) membrane or an electrode. Two types of electro
      convection in strong electrolytes may be distinguished: bulk electro-convection,
      due to the action of the electric field upon the residual space charge of a quasi
      electro-neutral bulk solution, and convection induced by electroosmotic slip, due
      to electric forces acting in the thin electric double layer of either quasi
      equilibrium or non-equilibrium type near the solid/liquid interface. According to
      recent studies, the latter appears to be the likely source of mixing in the
      diffusion layer, leading to 'over-limiting' conductance in electrodialysis.
      Electro-convection near a planar uniform charge selective solid/liquid interface
      sets on as a result of hydrodynamic instability of one-dimensional steady state
      electric conduction through such an interface. We compare the results of linear
      stability analysis obtained for instabilities of this kind appearing in the full
      electro-convective and limiting non-equilibrium electroosmotic formulations. The
      short- and long-wave aspects of these instabilities are discussed along with the
      wave number selection principles.

PMID- 17559787
TI  - The long-term effect of vitreous presentation during extracapsular cataract
      surgery on postoperative visual acuity.
AB  - PURPOSE: To compare at two, three, and four years after surgery the effect on
      best-corrected visual acuity (BCVA) of anterior chamber (AC) intraocular lenses
      (IOLs) and posterior chamber (PC) IOLs implanted after vitreous presentation (VP)
      during extracapsular cataract extraction in patients having sufficient capsular
      support for a nonsutured PC IOL. DESIGN: The study was a randomized prospective,
      long-term, clinical trial. METHODS: Patients at 19 Department of Veterans Affairs
      Medical Centers having VP during cataract surgery with sufficient capsular
      support were randomized to receive either a PC IOL (230 patients) or an AC IOL
      (208 patients). Patients having insufficient capsular support (ICS; 143 patients)
      and a 5% random sample of nonvitreous presentation patients (NVP; 521 patients)
      were prospectively followed in the same fashion. RESULTS: There was no
      significant difference on the major outcome measure of BCVA of 20/40 or better
      between the PC IOL and AC IOL groups at two (88.7% vs 82.2%; P = .23), three
      (82.5% vs 91.8%; P = .18), and four (88.6% vs 92.6%; P = .69) years of follow-up.
      The ICS patients had significantly worse (P < .0083) or a trend to be worse (P <
      .05) BCVA of 20/40 or better than the other three groups at two and four years.
      CONCLUSIONS: The significant difference that the PC IOL was better than the AC
      IOL on the major outcome measure at one year reported previously was not
      maintained in later years. The poor results for ICS patients reported previously
      at one year continue at two and four years.

PMID- 17559788
TI  - Large-scale preparation of human low- and high-density lipoproteins by density
      gradient centrifugation using iodixanol.

PMID- 17559789
TI  - Atmospheric influence on the background of luminol-based chemiluminescent assays.

PMID- 17559791
TI  - Isotopologue distributions of peptide product ions by tandem mass spectrometry:
      quantitation of low levels of deuterium incorporation.
AB  - Protonated molecular peptide ions and their product ions generated by tandem mass
      spectrometry appear as isotopologue clusters due to the natural isotopic
      variations of carbon, hydrogen, nitrogen, oxygen, and sulfur. Quantitation of the
      isotopic composition of peptides can be employed in experiments involving isotope
      effects, isotope exchange, and isotopic labeling by chemical reactions and in
      studies of metabolism by stable isotope incorporation. Both ion trap and
      quadrupole-time of flight mass spectrometry are shown to be capable of
      determining the isotopic composition of peptide product ions obtained by tandem
      mass spectrometry with both precision and accuracy. Tandem mass spectra of
      clusters of isotopologue ions obtained in profile mode are fit by nonlinear least
      squares to a series of Gaussian peaks which quantify the Mn/M0 values which
      define the isotopologue distribution (ID). To determine the isotopic composition
      of product ions from their ID, a new algorithm that predicts the Mn/M0 ratios and
      obviates the need to determine the intensity of all of the ions of an ID is
      developed. Consequently a precise and accurate determination of the isotopic
      composition of a product ion may be obtained from only the initial values of the
      ID, however, the entire isotopologue cluster must be isolated prior to
      fragmentation. Following optimization of the molecular ion isolation width,
      fragmentation energy, and detector sensitivity, the presence of isotopic excess
      (2H, 13C, 15N, 18O) is readily determined within 1%. The ability to determine the
      isotopic composition of sequential product ions permits the isotopic composition
      of individual amino acid residues in the precursor ion to be determined.

PMID- 17559790
TI  - Specific derivatization of the vesicle monoamine transporter with novel carrier
      free radioiodinated reserpine and tetrabenazine photoaffinity labels.
AB  - Two iodophenylazide derivatives of reserpine and one iodophenylazide derivative
      of tetrabenazine have been synthesized and characterized as photoaffinity labels
      of the vesicle monoamine transporter (VMAT2). These compounds are 18-O-[3-(3'
      iodo-4'-azidophenyl)-propionyl]methyl reserpate (AIPPMER), 18-O-[N-(3'-iodo-4'
      azidophenethyl)glycyl]methyl reserpate (IAPEGlyMER), and 2-N-[(3'-iodo-4'
      azidophenyl)-propionyl]tetrabenazine (TBZ-AIPP). Inhibition of [3H]dopamine
      uptake into purified chromaffin granule ghosts showed IC50 values of
      approximately 37 nM for reserpine, 83 nM for AIPPMER, 200 nM for IAPEGlyMER, and
      2.1 microM for TBZ-AIPP. Carrier-free radioiodinated [125I]IAPEGlyMER and
      [125I]TBZ-AIPP were synthesized and used to photoaffinity label chromaffin
      granule membranes. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS
      PAGE) analysis showed specific [125I]IAPEGlyMER labeling of a polypeptide that
      migrated as a broad band (approximately 55-90 kDa), with the majority of the
      label located between 70 and 80 kDa. The labeling by [125I]IAPEGlyMER was blocked
      by 100 nM reserpine, 10 microM tetrabenazine, 1 mM serotonin, and 10 mM (-)
      norepinephrine and dopamine. Analysis of [125I]TBZ-AIPP-labeled chromaffin
      granule membranes by SDS-PAGE and autoradiography demonstrated specific labeling
      of a similar polypeptide, which was blocked by 1 microM reserpine and 10 microM
      tetrabenazine. Incubation of [125I]TBZ-AIPP-photolabeled chromaffin granule
      membranes in the presence of the glycosidase N-glycanase shifted the apparent
      molecular weight of VMAT2 to approximately 51 kDa. These data indicate that
      [125I]IAPEGlyMER and [125I]TBZ-AIPP are effective photoaffinity labels for VMAT2.

PMID- 17559792
TI  - Adrenal tuberculosis after a pheochromocytoma: a misleading tumoral presentation.
AB  - Adrenal gland involvement could account for 6% of active tuberculosis. The
      diagnosis of this extrapulmonary form of tuberculosis is difficult, especially
      when presenting as unilateral adrenal tumor. This report describes an unusual
      case of adrenal tuberculosis presenting as a tumor occurring shortly after
      surgical removal of an adrenal pheochromocytoma located in the opposite gland, in
      a 63-year-old woman with a previous history of breast cancer. At initial
      presentation, the patient suffered from symptomatic paroxysmal hypertension. A
      pheochromocytoma in the left adrenal was diagnosed and resected. One year later,
      while physical examination and biological parameters were unremarkable, an
      enhanced adrenal computed tomography (CT) scan showed a right adrenal mass
      mimicking the CT features of the resected pheochromocytoma. A peripheral tissular
      rim delineating a central hypodensity characterized this tumor. Magnetic
      resonance imaging (MRI) showed the same findings on gadolinium-enhanced T1
      weighted slices, while the mass was not seen on T2-weighted images. No tumoral
      signal loss was observed on out of phase images when using the in phase-out of
      phase T1-weighted sequence. Because of the tumoral evolution and the uncertainty
      of the nature of that lesion, the patient underwent a second adrenalectomy.
      Definitive diagnosis was provided by culture of tissue sample, which resulted in
      the identification of Mycobacterium tuberculosis. In an era of tuberculosis
      resurgence, this unusual case underscores the necessity of keeping in mind
      adrenal tuberculosis as a possible differential diagnosis in adrenal tumors of
      uncertainty nature. It stresses the importance of culture of biopsy tumor,
      whenever feasible, to avoid unnecessary operations. In the near future,
      interferon-gamma assay could be a valuable means to recognize extrapulmonary
      forms of tuberculosis.

PMID- 17559793
TI  - Differentiation-dependent expression of Adhfe1 in adipogenesis.
AB  - We have determined that adipocytes are a major site of expression of the
      transcript for the novel alcohol dehydrogenase (ADH), Adhfe1. Adhfe1 is unique in
      that the sequence of its encoded protein places it among the iron-activated ADHs.
      Western blot analysis reveals Adhfe1 encodes a 50 kDa protein and
      immunocytochemical staining indicates mitochondrial localization. Adhfe1
      transcript exhibits differentiation-dependent expression during in vitro brown
      and white adipogenesis. Unlike many adipocyte-enriched genes, however, Adhfe1
      transcript expression in adipocytes is refractory to TNFalpha-mediated
      downregulation. However, use of pharmacological inhibitors reveals PI 3-kinase
      mediated signals maintain the basal level of Adhfe1 transcript in 3T3-L1
      adipocytes. Tissue profiling studies show Adhfe1 transcript is restricted to
      white and brown adipose tissues, liver, and kidney. In comparison to C57BL/6
      mice, Adhfe1 transcript is downregulated 40% in white adipose tissue of ob/ob
      obese mice. Further characterization of Adhfe1 should yield new insights into
      adipocyte function and energy metabolism.

PMID- 17559795
TI  - Effect of iron on acid demineralisation of bovine enamel blocks by a soft drink.
AB  - OBJECTIVES: The aim of this study was to evaluate, in vitro, the effect of iron
      on the acid demineralisation of bovine enamel blocks by a soft drink. DESIGN:
      Twenty-four blocks of bovine enamel were randomly assigned to two groups
      (experimental and control), which were exposed to 4 cycles of demineralisation in
      Coke containing or not 10 mmol/L of iron, respectively, and another 4 cycles of
      remineralisation in artificial saliva. The softening of enamel was evaluated by %
      superficial microhardness change (SMHC) and wear analysis. Data were analysed
      using t-test (p<0.05). RESULTS: With regard to %SMHC, the experimental group
      presented average values (+/-S.E.) of -85.3+/-0.9, that were significantly higher
      (t=4.7, p<0.01) than the ones observed for control group (-76.7+/-1.6). The
      experimental group presented a mean wear (+/-S.E.) of 2.3+/-0.2 microm, that was
      significantly lesser (t=3.7, p<0.01) than the one observed for the control group
      (3.5+/-0.2 microm). CONCLUSIONS: According to this protocol, iron at 10 mmol/L
      significantly reduced the wear, but significantly enhanced the %SMHC of enamel
      blocks submitted to erosion by Coke.

PMID- 17559794
TI  - Potency of a tau fibrillization inhibitor is influenced by its aggregation state.
AB  - Tau fibrillization is a potential therapeutic target for Alzheimer's and other
      neurodegenerative diseases. Several small-molecule inhibitors of tau aggregation
      have been developed for this purpose. One of them, 3,3'-bis(beta-hydroxyethyl)-9
      ethyl-5,5'-dimethoxythiacarbocyanine iodide (N744), is a cationic
      thiacarbocyanine dye that inhibits recombinant tau filament formation when
      present at submicromolar concentrations. To prepare dosing regimens for testing
      N744 activity in biological models, its full concentration-effect relationship in
      the range 0.01-60muM was examined in vitro by electron microscopy and laser light
      scattering methods. Results revealed that N744 concentration dependence was
      biphasic, with fibrillization inhibitory activity appearing at submicromolar
      concentration, but with relief of inhibition and increases in fibrillization
      apparent above 10muM. Therefore, fibrillization was inhibited 50% only over a
      narrow concentration range, which was further reduced by filament stabilizing
      modifications such as tau pseudophosphorylation. N744 inhibitory activity also
      was paralleled by changes in its aggregation state, with dimer predominating at
      inhibitory concentrations and large dye aggregates appearing at high
      concentrations. Ligand dimerization was promoted by the presence of tau protein,
      which lowered the equilibrium dissociation constant for dimerization more than an
      order of magnitude relative to controls. The results suggest that ligand
      aggregation may play an important role in both inhibitory and disinhibitory
      phases of the concentration-effect curve, and may lead to complex dose-response
      relationships in model systems.

PMID- 17559796
TI  - Relationship between lactate dehydrogenase activity in saliva and oral health
      status.
AB  - OBJECTIVE: Lactate dehydrogenase (LDH) activity in serum increases as a marker of
      cellular necrosis. LDH activity in saliva could constitute a specific indicator
      of oral mucosal lesions with tissue breakdown including periodontal disease. The
      aim of this study was to determine LDH activity in saliva, assessing inter
      individual variations with regard to the oral health status. MATERIALS AND
      METHODS: An oral and perioral examination was performed on a study group of 175
      volunteers, to assess the number of missing teeth, caries, fillings, dental
      prosthesis, periodontal status and temporomandibular joint condition. LDH
      activity was determined from stimulated whole saliva. RESULTS: After adjustment
      by age, gender, smoking habits, missing teeth and use of removable prosthesis,
      the multivariate analysis showed that increased LDH activity was associated with
      periodontal disease, specifically with the presence of calculus and pockets
      greater than 5mm. CONCLUSION: LDH activity in whole saliva could be useful as a
      biochemical marker of periodontal status.

PMID- 17559797
TI  - Oral bacterial lipopolysaccharide acts in mice to promote sensitisation to
      ovalbumin and to augment anaphylaxis via platelets.
AB  - Microbial infection is thought to modulate allergic disorders, and we previously
      demonstrated that not only mast cells (which release histamine), but also
      platelets are involved in the anaphylaxis induced in mice sensitised to ovalbumin
      (OVA). Here, we examined the effects of a lipopolysaccharide (LPS) from the oral
      bacterium Prevotella intermedia (Pi) on OVA-induced anaphylaxis. Upon
      intraperitoneal co-injection of Pi-LPS plus OVA into BALB/c mice, the Pi-LPS
      displayed a potent adjuvant effect comparable to that of alum (a standard
      adjuvant) in terms of its abilities to induce both anaphylactic shock and
      histamine-release following an antigen (OVA)-challenge. Moreover, an injection of
      Pi-LPS given to OVA+alum-sensitised mice shortly before an OVA-challenge
      augmented the shock-response. This LPS-pretreatment did not affect histamine
      release, but did augment pulmonary platelet accumulation. Histamine was not by
      itself causal for shock-induction in sensitised mice. These results suggest that
      oral bacteria and/or their constituents (such as LPS) may help to sensitise the
      host to an antigen or exacerbate the host's allergic reactions ("aggravation
      effect"), probably by enhancing the platelet response to the antigen OVA.

PMID- 17559798
TI  - Evidence for amylase release by cGMP via cAMP-dependent protein kinase in rat
      parotid acinar cells.
AB  - Amylase release from the rat parotid gland is primarily mediated by a cAMP
      dependent protein kinase (PKA). We previously reported that cGMP/cGMP-dependent
      protein kinase (PKG) signaling evokes amylase release. In the present study, we
      investigated whether cGMP-mediated amylase release might be due to cGMP/PKA
      signaling, as well as cGMP/PKG pathway. Activation of PKA by cGMP was required
      100-1000-fold greater concentration than activation by cAMP in a parotid cytosol
      fraction. Synergistic activation of PKA by the combination of physiological cAMP
      and low concentration of cGMP was observed. Amylase release from intact acinar
      cells was synergistically stimulated by the combination of diBu-cAMP and 8-pCPT
      cGMP. cGMP dose-dependently stimulated amylase release from saponin-permeabilized
      parotid acinar cells. Phosphorylation by cGMP produced phosphorylated proteins of
      the same size as those produced by cAMP. Phosphorylation by cGMP was inhibited by
      the addition of PKA inhibitor, H-89. These results suggest that cGMP activates
      both PKG and PKA. Thus, it appears that both cGMP/PKG and cGMP/PKA pathways
      mediate amylase release from rat parotid acinar cells.

PMID- 17559799
TI  - Proton flux through the chloroplast ATP synthase is altered by cleavage of its
      gamma subunit.
AB  - Electron transport, the proton gradient and ATP synthesis were determined in
      thylakoids that had been briefly exposed to a low concentration of trypsin during
      illumination. This treatment cleaves the gamma subunit of the ATP synthase into
      two large fragments that remain associated with the enzyme. Higher rates of
      electron transport are required to generate a given value of the proton gradient
      in the trypsin-treated membranes than in control membranes, indicating that the
      treated membranes are proton leaky. Since venturicidin restores electron
      transport and the proton gradient to control levels, the proton leak is through
      the ATP synthase. Remarkably, the synthesis of ATP by the trypsin-treated
      membranes at saturating light intensities is only slightly inhibited even though
      the proton gradient is significantly lower in the treated thylakoids. ATP
      synthesis and the proton gradient were determined as a function of light
      intensity in control and trypsin-treated thylakoids. The trypsin-treated
      membranes synthesized ATP at lower values of the proton gradient than the control
      membranes. Cleavage of the gamma subunit abrogates inhibition of the activity of
      the chloroplast ATP synthase by the epsilon subunit. Our results suggest that
      overcoming inhibition by the epsilon subunit costs energy.

PMID- 17559800
TI  - Natural lipid extracts and biomembrane-mimicking lipid compositions are disposed
      to form nonlamellar phases, and they release DNA from lipoplexes most
      efficiently.
AB  - A viewpoint now emerging is that a critical factor in lipid-mediated transfection
      (lipofection) is the structural evolution of lipoplexes upon interacting and
      mixing with cellular lipids. Here we report our finding that lipid mixtures
      mimicking biomembrane lipid compositions are superior to pure anionic liposomes
      in their ability to release DNA from lipoplexes (cationic lipid/DNA complexes),
      even though they have a much lower negative charge density (and thus lower
      capacity to neutralize the positive charge of the lipoplex lipids). Flow
      fluorometry revealed that the portion of DNA released after a 30-min incubation
      of the cationic O-ethylphosphatidylcholine lipoplexes with the anionic
      phosphatidylserine or phosphatidylglycerol was 19% and 37%, respectively, whereas
      a mixture mimicking biomembranes (MM:
      phosphatidylcholine/phosphatidylethanolamine/phosphatidylserine /cholesterol
      45:20:20:15 w/w) and polar lipid extract from bovine liver released 62% and 74%,
      respectively, of the DNA content. A possible reason for this superior power in
      releasing DNA by the natural lipid mixtures was suggested by structural
      experiments: while pure anionic lipids typically form lamellae, the natural lipid
      mixtures exhibited a surprising predilection to form nonlamellar phases. Thus,
      the MM mixture arranged into lamellar arrays at physiological temperature, but
      began to convert to the hexagonal phase at a slightly higher temperature,
      approximately 40-45 degrees C. A propensity to form nonlamellar phases
      (hexagonal, cubic, micellar) at close to physiological temperatures was also
      found with the lipid extracts from natural tissues (from bovine liver, brain, and
      heart). This result reveals that electrostatic interactions are only one of the
      factors involved in lipid-mediated DNA delivery. The tendency of lipid bilayers
      to form nonlamellar phases has been described in terms of bilayer "frustration"
      which imposes a nonzero intrinsic curvature of the two opposing monolayers.
      Because the stored curvature elastic energy in a "frustrated" bilayer seems to be
      comparable to the binding energy between cationic lipid and DNA, the balance
      between these two energies could play a significant role in the lipoplex-membrane
      interactions and DNA release energetics.

PMID- 17559801
TI  - Structural organisation of prolamellar bodies (PLB) isolated from Zea mays.
      Parallel TEM, SAXS and absorption spectra measurements on samples subjected to
      freeze-thaw, reduced pH and high-salt perturbation.
AB  - Well-organised PLB gives rise to a X-ray diffraction pattern overlaid by a
      scattering pattern arising from individual tubules within less well-organised
      regions of the lattice. TEM and SAXS measurements were used to characterise the
      structural changes in PLB subjected to perturbation by freeze-thaw, exposure to
      pH 6.5, or resuspension in high-salt media. Comparison of SAXS patterns measured,
      before and after structural perturbation allows the separation of the
      contributions from ordered and disordered PLB. The diffraction pattern is shown
      to be based on a diamond cubic (Fd3m) lattice of unit cell a=78 nm. Freeze-thaw
      and high-salt disruption lead to the breakdown of ordered PLB into disordered
      tubules of similar dimensions to those making up the original PLB lattice. Their
      scattering patterns suggest that they are approximately 26 nm in diameter with a
      central lumen about 16 nm in diameter. The tubules formed at pH 6.5 are
      appreciably narrower, probably reflecting changes in the pattern of ionisation of
      charged groups at the membrane surface. Absorption spectra of PLB in media
      containing different concentrations of salts indicated that the structural and
      spectral changes are related. NADPH, have a significant role in the protection of
      POR-PChlide(650) but to have only a relatively small effect on the preservation
      of PLB organisation indicating that the retention of POR-PChlide(650) in isolated
      PLB preparations is a poor guide to their structural integrity.

PMID- 17559802
TI  - Lipid tail chain asymmetry and the strength of membrane-induced interactions
      between membrane proteins.
AB  - Many lipids are composed of asymmetric tail chains that differ by their molecular
      weight (MW) and/or degree of saturation. Previous studies found that membrane
      moduli vary with the degree of lipid tail asymmetry. However, to date little is
      known regarding the effect (if any) of tail asymmetry on the membrane-induced
      interactions between embedded proteins. In this paper we use a self-consistent
      field model to examine the effect of lipid tail asymmetry on membrane proteins.
      We first examine the case where the overall tail length (sum of both chains) is
      held constant, which implies that the membrane thickness remains constant as
      well, independent of tail asymmetry. We find that, in these systems, the membrane
      area stretch and bending moduli decrease with increasing chain asymmetry, thereby
      reducing the magnitude of the membrane-induced barrier to protein aggregation.
      Since in symmetric lipid bilayers the energy barrier is typically of order
      approximately 1-2 times the thermal energy kT, the asymmetry-induced reduction in
      barrier height may increase the probability of protein aggregation significantly.
      In systems where one tail chain is held constant, increasing asymmetry involves
      changes in the bilayer thickness which are found to dominate any effect arising
      from the asymmetry.

PMID- 17559803
TI  - Changes in quality of life following cognitive-behavioral therapy for obsessive
      compulsive disorder.
AB  - Cognitive-behavioral therapy (CBT) incorporating exposure and response prevention
      is a first line treatment for obsessive-compulsive disorder (OCD). Although, the
      efficacy of CBT in reducing OCD symptoms is well documented, less is known about
      its effects on quality of life (QOL). In the current study, functional impairment
      aspects of QOL (as measured by the Sheehan Disability Scale) were assessed among
      70 adult outpatients with OCD before and after CBT. Statistically significant
      improvements in QOL and large pre- to post-treatment effect sizes were observed
      for work, social, and family functioning. Improvements in social and family
      functioning were predicted by improvements in OCD symptom severity even after
      controlling for improvements in depressive symptoms. In addition, clinically
      significant change in OCD symptoms and QOL were highly related, although there
      was a subset of participants whose symptoms improved without corresponding
      improvements in QOL. These results suggest that the effects of CBT may extend
      beyond OCD symptom reduction to QOL.

PMID- 17559804
TI  - Inhibition of thioredoxin reductase induces apoptosis in neuronal cell lines:
      role of glutathione and the MKK4/JNK pathway.
AB  - The Thioredoxin (Trx)/Thioredoxin reductase (TrxR)-system has emerged as a
      crucial component of many cellular functions particularly antioxidant defence. We
      investigated the effect of the selective TrxR inhibitor 1-chloro-2,4
      dinitrobenzene (CDNB) on survival and redox status in neuronal cell lines. CDNB
      was found to cause apoptosis without depletion of glutathione or loss of
      mitochondrial complex I-activity. Cells treated with CDNB displayed an early
      increase of reactive oxygen species and rapid activation of stress inducible
      protein kinases c-Jun N-terminal kinase (JNK) and mitogen activated protein
      kinase kinase 4 (MKK4). Thus TrxR inhibition by CDNB results in generation of
      reactive oxygen species and subsequent activation of stress-inducible kinases
      without impairment of the cellular antioxidant status or mitochondrial function.
      Inhibition of the specific kinases involved in cell death triggered by Trx/TrxR
      dysfunction could represent a novel and selective therapeutic approach in
      neurodegenerative disorders.

PMID- 17559805
TI  - Development of a new Ca2+/calmodulin antagonist and its anti-proliferative
      activity against colorectal cancer cells.
AB  - We previously identified a cellular target of a cell cycle inhibitor HBC as
      Ca(2+)/calmodulin (Ca(2+)/CaM) through chemical genetics approach. Using the
      mechanism-based drug design, we developed a new Ca(2+)/CaM antagonists based on
      the structure of HBC. The compound, (4-{3,5-bis-[2-(4-hydroxy-3-methoxy-phenyl)
      vinyl]-4,5-dihydro-pyrazol-1-yl}-phenyl)-(4-methyl-piperazin-1-yl)-methanone
      (referred as HBCP), binds to Ca(2+)/CaM in vitro and inhibits the proliferation
      of HCT15 colon cancer cells. HBCP induced sustained phosphorylation of ERK1/2 and
      subsequently activated p21(WAF1) expression in HCT15 cells. Moreover, HBCP
      reversibly induced the G(0)/G(1) cell cycle arrest in the cells. These data
      demonstrate that HBCP is a new potent Ca(2+)/CaM antagonist and can be applied
      for CaM related therapeutic uses.

PMID- 17559806
TI  - CXCR4/CXCL12 axis promotes VEGF-mediated tumor angiogenesis through Akt signaling
      pathway.
AB  - CXC chemokine receptor 4 (CXCR4) has been shown to play a critical role in
      chemotaxis and homing, which are key steps in cancer metastasis. There is also
      increasing evidence that links this receptor to angiogenesis; however, its
      molecular basis remains elusive. Vascular endothelial growth factor (VEGF), one
      of the major angiogenic factors, promotes the formation of leaky tumor
      vasculatures that are the hallmarks of tumor progression. Here, we investigated
      whether CXCR4 induces the expression of VEGF through the PI3K/Akt pathway. Our
      results showed that CXCR4/CXCL12 induced Akt phosphorylation, which resulted in
      upregulation of VEGF at both the mRNA and protein levels. Conversely, blocking
      the activation of Akt signaling led to a decrease in VEGF protein levels;
      blocking CXCR4/CXCL12 interaction with a CXCR4 antagonist suppressed tumor
      angiogenesis and growth in vivo. Furthermore, VEGF mRNA levels correlated well
      with CXCR4 mRNA levels in patient tumor samples. In summary, our study
      demonstrates that the CXCR4/CXCL12 signaling axis can induce angiogenesis and
      progression of tumors by increasing expression of VEGF through the activation of
      PI3K/Akt pathway. Our findings suggest that targeting CXCR4 could provide a
      potential new anti-angiogenic therapy to suppress the formation of both primary
      and metastatic tumors.

PMID- 17559807
TI  - Estrogen has anti-amyloidogenic effects on Alzheimer's beta-amyloid fibrils in
      vitro.
AB  - Inhibition of the assembly of amyloid beta-peptide (Abeta) as well as the
      destabilization of preformed beta-amyloid fibrils (fAbeta) in the central nervous
      system could be valuable therapeutics of patients with Alzheimer's disease (AD).
      Epidemiological studies have indicated that estrogen therapy reduced the risk of
      developing AD in women. Here, we examined the effects of estrogen (estrone (E1),
      estradiol (E2), and estriol (E3)) and related sexual steroids (androstenedione
      (AND) and testosterone (TES)) on the polymerization, extension and
      destabilization of fAbeta(1-42) and fAbeta(1-40) at pH 7.5 at 37 degrees C in
      vitro, using fluorescence spectroscopic analysis with thioflavin T and electron
      microscopic studies. E1, E2, and E3 dose-dependently inhibited the formation, as
      well as destabilization of fAbetas. The overall anti-amyloidogenic activity of
      these molecules was in the order of: E3>E2=E1>>AND=TES. Estrogen could be a
      potential therapeutic agent to prevent or delay AD progression.

PMID- 17559808
TI  - Angiopoietin-1 protects H9c2 cells from H2O2-induced apoptosis through AKT
      signaling.
AB  - Loss of cardiomyocytes by apoptosis is proposed to cause ventricular remodeling
      and heart failure. Reactive oxygen species-induced apoptosis of cardiomyocytes
      has been reported to play an important role in many types of pathological
      processes of the heart. We investigated whether angiopoietin-1 (Ang1) has direct
      cytoprotective effects on cardiomyocytes against oxidative stress. Cultured H9c2
      cells (cardiomyocytes) were treated with hydrogen peroxide (H(2)O(2)). Apoptosis
      was evaluated by flow cytometry, TUNEL assay and DNA laddering. The H(2)O(2)
      treatment caused typical apoptosis of H9c2 cells in a time-dependent manner.
      Transfection of recombinant adenovirus expressing Ang1 resulted in a sustained
      phosphorylation of AKT and inhibition of H(2)O(2)-induced apoptosis in H9c2
      cells. This effect could be reversed by AKT inhibition. These results suggest
      that Ang1 protects cardiomyocytes from oxidative stress-induced apoptosis by
      regulating the activity of AKT.

PMID- 17559809
TI  - Clock controls timing of mouse pancreatic differentiation through regulation of
      Wnt- and Notch-based and cell division components.
AB  - The oscillations of circadian genes control the daily circadian clock, regulating
      a diverse array of physiologies with the 24-hour light/dark cue across a wide
      variety of organisms. Here we first show that before embryonic circadian rhythms
      occur, the oscillation (nucleocytoplasmic shuttling) of core circadian gene Clock
      is tissue-specific and correlated with the state of differentiation during both
      early development and later pancreas organogenesis. Disruption of Clock as well
      as Timeless in the embryonic pancreas does not block pancreatic differentiation
      but alters the balance and maturity of endocrine and exocrine cells. Molecular
      analysis indicates that inhibition of Clock or Timeless expression disturbs not
      only cell cycle regulators, but also Wnt- and Notch-signaling components, whose
      oscillations establish the timing mechanism in somitogenesis. Thus, our results
      provide new insights about circadian genes' function in control of the timing of
      differentiation during embryonic development.

PMID- 17559810
TI  - Localization and effect of ectopic expression of CPT1c in CNS feeding centers.
AB  - Hypothalamic neurons monitor peripheral energy status and produce signals to
      adjust food intake and energy expenditure to maintain homeostasis. However, the
      molecular mechanisms by which these signals are generated remain unclear.
      Fluctuations in the level of hypothalamic malonyl-CoA are known to serve as an
      intermediary in regulating energy homeostasis and it has been proposed that the
      brain-specific carnitine palmitoyltransferase-1c (CPT1c) serves as a target of
      malonyl-CoA in the central nervous system (CNS). Here, we report that CPT1c is
      widely expressed in neurons throughout the CNS including the hypothalamus,
      hippocampus, cortex, and amygdala. CPT1c is enriched in neural feeding centers of
      the hypothalamus with mitochondrial localization as an outer integral membrane
      protein. Ectopic over-expression of CPT1c by stereotactic hypothalamic injection
      of a CPT1c adenoviral vector is sufficient to protect mice from body weight gain
      when fed a high-fat diet. These findings show that CPT1c is appropriately
      localized in regions and cell types to regulate energy homeostasis and that its
      over-expression in the hypothalamus is sufficient to protect mice from adverse
      weight gain caused by high-fat intake.

PMID- 17559811
TI  - p53 dependent and independent sensitivity to oxaliplatin of colon cancer cells.
AB  - Oxaliplatin is an efficient chemotherapeutic agent used for the treatment of
      metastatic human colon cancer, but cancer cells are frequently resistant. The aim
      of this study was to analyse the underlying mechanisms in a panel of 10 human
      colorectal cancer cell lines submitted to a short (2h) oxaliplatin treatment
      period, accordingly to the usual therapeutic procedure in humans. Sensitivity to
      oxaliplatin was a characteristic of p53 wild-type colon cancer cells. In
      contrast, all p53-mutated cell lines had a high IC50 to oxaliplatin, with the
      exception of the V9P cell line. Exposure to oxaliplatin resulted in G0/G1 arrest
      in p53 wild-type cell lines, and in S phase in p53-mutated cell lines. In our
      treatment conditions, no DNA accumulation in sub G0/G1 phase, no caspase-3
      activation nor PARP cleavage were detected after oxaliplatin treatment, except
      for the V9P cell line. The major role of the p53-p21 pathway in oxaliplatin
      sensitivity was confirmed in the p53 wild-type HCT116 cell line, using siRNA
      duplex, and knockdown of the TAp73 protein also enhanced resistance to
      oxaliplatin in this cell line. Surprisingly, siRNA duplex invalidation revealed a
      residual effect of the mutant p53 protein in p53-mutated cell lines. Persistent
      sensitivity to oxaliplatin of the p53-mutated V9P cell line was associated with
      oxalipatin-induced apoptosis but TAp73 was not the responsible alternative
      pathway.

PMID- 17559812
TI  - Disruption of HDAC4/N-CoR complex by histone deacetylase inhibitors leads to
      inhibition of IL-2 gene expression.
AB  - Previous studies have shown that HDAC inhibitors selectively inhibit IL-2 gene
      expression, but the mechanism of this inhibition remains to be elucidated. It was
      recently reported that HDAC4, a component of the nuclear hormone receptor
      corepressor (N-CoR) complex, associates with the IL-2 promoter via the
      transcription factor myocyte enhancer factor 2 (MEF2). We therefore focused on
      the role of HDAC4/N-CoR complex in the transcriptional regulation of IL-2. Four
      approaches were used to characterize this role and to investigate the relation
      between the regulatory function of HDAC4/N-CoR complex and HDAC4-enzymatic
      activity: (i) HDAC4 silencing by RNA interference, (ii) overexpression of N-CoR
      repression domain 3 (RD3), (iii) overexpression of HDAC4 point mutants, and (iv)
      treatment with HDAC inhibitors. Here, we report that HDAC4 plays an essential
      role in IL-2 promoter activation, and that the formation of the HDAC4/N-CoR
      complex, which is closely related to HDAC4-enzymatic activity, might be involved
      in HDAC inhibitor-mediated inhibition of IL-2 gene expression. These observations
      indicate that the selective inhibition of HDAC4 or the interaction of HDAC4 with
      N-CoR is likely a potential target for the development of novel
      immunosuppressants.

PMID- 17559813
TI  - alphaCaMKII autophosphorylation levels differ depending on subcellular
      localization.
AB  - Calcium/calmodulin-dependent protein kinase II (CaMKII) has important roles in
      many processes in the central nervous system. It is enriched at the post-synaptic
      density (PSD), a localization which is thought to be critical for many of its
      proposed neuronal functions. In order to better understand the mechanisms that
      regulate association of CaMKII with the PSD, we compared the levels of
      autophosphorylation between PSD-associated kinase and kinase in other parts of
      the neuron. We were surprised to find that alphaCaMKII in a PSD-enriched fraction
      prepared from recovered hippocampal CA1-minislices had a relatively low level of
      threonine 286 (T286) phosphorylation and a relatively high level of threonine 305
      (T305) phosphorylation. Furthermore, when the minislices were subjected to a
      treatment that mimics ischemic conditions, there was a significant translocation
      of alphaCaMKII to the PSD-enriched fraction accompanied with a dramatic reduction
      in T286 phosphorylation levels throughout the neuron. These findings have
      important implications for our understanding of the role of autophosphorylation
      in the localization of CaMKII.

PMID- 17559814
TI  - Altered cerebral glucose metabolism in an animal model of diabetes insipidus: a
      micro-PET study.
AB  - The Brattleboro rat is an animal model of genetically induced central diabetes
      insipidus. These rats show cognitive and behavioral disorders, but no
      neurodegenerative disease has been observed. We studied brain glucose uptake, a
      marker of neuronal activity, in 6 Brattleboro rats, in comparison with 6 matched
      Long-Evans (LE) control rats. A group of 3 Brattleboro rats and 3 Long-Evans rats
      was studied in vivo and another group of animals was studied ex vivo. In vivo
      studies were performed using fluorodeoxyglucose labeled with fluorine 18 ((18)F
      FDG) and a dedicated small-animal PET device. At 30 min and 60 min p.i., (18)F
      FDG uptake was significantly higher in the frontal cortex, striatum, thalamus and
      cerebellum of Brattleboro rats than in LE rats when measured by PET in vivo
      (p<0.05), but only a trend towards higher values was found ex vivo. Our results
      show for the first time that brain glucose metabolism is modified in Brattleboro
      rats. This altered brain glucose metabolism in Brattleboro rats may be related to
      the observed cognitive and behavioral disorders. Functional analyses of brain
      metabolism are promising to investigate cognitive behavioral disturbances
      observed in Brattleboro rats and their link to diabetes insipidus.

PMID- 17559815
TI  - Modulation of long-interval intracortical inhibition and the silent period by
      voluntary contraction.
AB  - Transcranial magnetic stimulation was used to examine the effect of voluntary
      contraction on the magnitude of long-interval intracortical inhibition (LICI) and
      the duration of the silent period in intrinsic hand muscles. The magnitude of
      LICI acting on the first dorsal interosseus (FDI) measured with a paired-pulse
      protocol with an inter-pulse interval of 100 ms decreased with increasing tonic
      level of voluntary abduction force generated by the index finger. LICI in
      abductor pollicis brevis (APB) decreased from the condition in which the index
      finger was at rest to the conditions in which it was abducted, whereas LICI in
      abductor digiti minimi (ADM) was unaffected by the level of index finger
      abduction. During voluntary abduction of the index finger, the magnitude of LICI
      was least in FDI, intermediate in ADM, and greatest in APB, suggesting that it
      may be a mechanism by which tonic activation of hand muscles is fractionated. The
      magnitude of LICI increased with conditioning stimulus intensity, but intensity
      did not interact with abduction force. The duration of the silent period (SP) in
      FDI decreased with the level of voluntary index finger abduction and increased
      with eliciting stimulus intensity. Within-subject correlations showed that the
      effects of voluntary drive on SP duration and motor-evoked potential amplitude
      did not covary, implying an indirect effect of voluntary drive on SP duration. It
      is proposed that whereas voluntary drive directly reduces the magnitude of slow
      acting inhibition acting on the active movement representations and near
      neighbors, sensory feedback from the contracting muscle acts to limit its time
      course.

PMID- 17559816
TI  - Functional neuroanatomy of the perception of modern art: A DC-EEG study on the
      influence of stylistic information on aesthetic experience.
AB  - The present study was conducted to determine the functional neuroanatomical
      correlates of aesthetic experience using slow cortical potentials (SCPs). Thirty
      participants without any particular background in the fine arts were presented
      with various representational (semi-abstract) and abstract paintings dating from
      the 20th and 21st century in two experimental conditions, i.e. with or without
      stylistic information. The paintings had to be rated by the participants in terms
      of understanding and aesthetic qualities. In order to identify the cortical
      structures involved, the SCPs were subjected to current density analysis using
      low-resolution electromagnetic tomography (LORETA). The comparison of
      representational and abstract paintings revealed significantly higher activation
      for representational artworks in several regions of the brain, predominantly in
      the left frontal lobe and bilaterally in the temporal lobes. According to the
      participants' reports, the representational artwork stimuli evoked more
      associations, accompanied by stronger activation of multimodal association areas
      in the temporal lobe. Furthermore, without stylistic information, the stimuli
      evoked stronger activation mainly in the left frontal and parietal lobes. Results
      also showed that stylistic information led to a better understanding of the
      paintings, but resulted in reduced cortical activation in the left hemisphere.
      This might have been due to less verbally oriented processing. These observations
      help explain the difficulties many beholders often have in appreciating abstract
      artworks.

PMID- 17559817
TI  - gem-Difluoro-carbasugars, the cases of mannopyranose and galactopyranose.
AB  - 5a-Difluoro-5a-carbamannopyranose (gem-difluoro-carbamannopyranose) and 5a
      difluoro-5a-carbagalactopyranose (gem-difluoro-carbagalactopyranose), close
      congeners of their respective natural sugars, in which the endocyclic oxygen atom
      has been replaced by a gem-difluoromethylene group, were synthesized from D
      mannose and D-galactose, using a rearrangement strategy.

PMID- 17559818
TI  - Synthesis of mono- and dideoxygenated alpha,alpha-trehalose analogs.
AB  - In this work, we describe the synthesis and NMR characterization of four mono-
      and four dideoxygenated analogs of alpha,alpha-D-trehalose. The symmetrical (2,2'
      , 3,3'-, 4,4'- and 6,6'-) dideoxy analogs were obtained via selective protection
      and subsequent radical deoxygenation of the desired hydroxyl group set. The
      unsymmetrical (2'-, 3'-, 4'- and 6'-) monodeoxy analogs were synthesized by
      desymmetrization of alpha,alpha-trehalose and subsequent deoxygenation under
      radical conditions. Complete assignment of all (1)H and (13)C resonances in the
      spectra of these deoxytrehaloses was achieved through the extensive use of 2D
      [(1)H,(1)H] and [(1)H,(13)C] correlation NMR experiments. The synthesis of these
      trehalose analogs sets the stage for future biochemical and NMR-based studies to
      probe the substrate interactions of trehalose with the recently identified
      mycobacterial sulfotransferase Stf0.

PMID- 17559819
TI  - Structure of a colitose-containing O-polysaccharide from the lipopolysaccharide
      of Providencia alcalifaciens O6.
AB  - The O-polysaccharide was isolated by mild acid degradation of the
      lipopolysaccharide of Providencia alcalifaciens O6 and studied by sugar and
      methylation analysis, selective hydrolytic removal of 3,6-dideoxy-L-xylo-hexose
      (colitose, Col), (1)H and (13)C NMR spectroscopy, including 2D (1)H,(1)H COSY,
      TOCSY, ROESY and H-detected (1)H,(13)C HSQC and HMBC experiments. The
      polysaccharide was found to have a branched pentasaccharide repeating unit with
      the following structure: [see text] Remarkably, the trisaccharide side chain of
      the O6-polysaccharide represents a colitose ('3-deoxy-L-fucose') analogue of the
      H type 1 (precursor) antigenic determinant.

PMID- 17559820
TI  - Concise synthesis of clarhamnoside, a novel glycosphingolipid isolated from the
      marine sponge Agela clathrodes.
AB  - The first total synthesis of a novel alpha-galactoglycosphingolipid clarhamnoside
      has been achieved through a straightforward strategy. A thiogalactosyl donor with
      a benzylidene group at C-4 and C-6 and nonparticipating p-methoxybenzyl group at
      C-2 was successfully employed in the stereocontrolled syntheses of alpha-GalGSLs.
      The N-Phth-protected trifluoroacetimidate donor for terminal disaccharide was
      successfully applied in constructing the [GalNAc beta-(1-->6)-Gal] glycosidic
      linkage.

PMID- 17559821
TI  - Zwitterionic glycosidase inhibitors: salacinol and related analogues.
AB  - Natural products with interesting biological properties and structural diversity
      have often served as valuable lead drug candidates for the treatment of human
      diseases. Salacinol, a naturally occurring alpha-glucosidase inhibitor, was shown
      to be one of the active principles of the aqueous extract of a medicinal plant
      that has been prescribed traditionally as an Ayurvedic treatment for type II
      diabetes. Salacinol contains an intriguing zwitterionic sulfonium-sulfate
      structure that comprises a 1,4-anhydro-4-thio-D-arabinitol core and a
      polyhydroxylated acyclic chain. Due to the unique structural features and its
      potential to become a lead drug candidate in the treatment of type II diabetes, a
      great deal of attention has been focused on salacinol and its analogues. Since
      the isolation of salacinol, several papers describing various synthetic routes to
      salacinol and its analogues have appeared in the literature. This review is aimed
      at highlighting the synthetic aspects of salacinol and related compounds as well
      as their structure-activity relationship studies.

PMID- 17559822
TI  - Nitric oxide cell signaling: S-nitrosation of Ras superfamily GTPases.
AB  - The Ras superfamily of small GTPases cycle between inactive GDP-bound and active
      GTP-bound states to modulate a diverse array of processes involved in cellular
      growth control. While the basic mechanisms by which GTPase regulatory proteins
      regulate GTPase substrates have been revealed through numerous studies, detailed
      studies into the mechanism(s) of free radical-mediated GTPase regulation have
      only more recently been tackled. This article reviews the mechanism of free
      radical-mediated GTPase regulation and shows nitric oxide can serve as important
      regulator of small GTPase proteins (i.e. Ras and RhoA) through protein
      modifications such as S-nitrosation.

PMID- 17559823
TI  - Asymmetric dimethyl L-arginine (ADMA) is a critical regulator of myocardial
      reperfusion injury.
AB  - OBJECTIVE: Endothelial dysfunction by the loss of nitric oxide (NO) is a critical
      event during reperfusion of ischemic myocardium. Reduced NO availability signals
      important pathophysiological changes leading to myocardial reperfusion injury. We
      have recently shown that NO biosynthesis can be disturbed by the endogenous NO
      synthase (NOS) inhibitor ADMA and that these changes are mediated by an
      impairment of its metabolism by dimethylarginine dimethylaminohydrolase (DDAH).
      We therefore analyzed the role of ADMA and its metabolism in the setting of
      myocardial ischemia and reperfusion. METHODS: C57-bl6 mice underwent myocardial
      ischemia for exactly 30 min followed by 2, 4, 8, 12, 24, and 72 h of reperfusion
      achieved by occlusion and re-opening of the left coronary artery. The reperfused
      left ventricle was subsequently homogenized for measurements of determinants of
      the NO synthase pathway. Furthermore, the effects and its mechanisms of ADMA on
      reperfusion injury were analyzed in a genetic mouse model. RESULTS: A significant
      accumulation of ADMA was found in myocardial tissue when mice were subjected to
      30 min of ischemia followed by reperfusion in our in vivo model. The maximum
      increase of tissue ADMA at 4 h of reperfusion coincided with reductions of NO
      tissue concentrations and DDAH activity; protein expression of NOS isoforms,
      however, was not changed. Furthermore, DDAH overexpression in a genetic mouse
      model as well as treatment with oral L-arginine markedly reduced reperfusion
      injury by 40-50% at 4 h of reperfusion. The effects of ADMA on reperfusion injury
      were shown to be mediated by reduced eNOS activity and phosphorylation,
      expression of adhesion molecules, and leukocyte activity. CONCLUSION:
      Accumulation of tissue ADMA by impairment of DDAH was found to be a significant
      determinant of reperfusion injury. Our results indicate that ADMA could be a
      potential new target for the treatment of myocardial ischemia/reperfusion injury.

PMID- 17559824
TI  - Loss of myocardial LIF receptor in experimental heart failure reduces
      cardiotrophin-1 cytoprotection. A role for neurohumoral agonists?
AB  - OBJECTIVES: Cardiomyocyte loss is involved in the transition from compensatory
      left ventricular hypertrophy (LVH) to heart failure (HF). Our aim was to
      investigate the status of the leukaemia inhibitory factor receptor (LIFR)/gp130
      survival pathway and its cytoprotective activity in intact cardiac tissue and in
      cardiomyocytes obtained from adult spontaneously hypertensive rats (SHR) with LVH
      (non-failing SHR) and from aged SHR with overt HF (failing SHR). METHODS: Cardiac
      morphometry was assayed by planimetry in an image analysis system. mRNA and
      protein expression were quantified by real time RT-PCR and Western blotting.
      Receptors were localized by immunocytochemistry. Trypan blue staining, TUNEL, and
      MTT cell viability assays were employed to study the cytoprotective activity of
      cardiotrophin-1 (CT-1) in isolated caridomyocytes. RESULTS: Compared to non
      failing SHR, failing SHR exhibited enhanced myocardial cell death (p<0.01)
      demonstrated by the increase in Bax/Bcl-2 ratio, caspase-3 activation and poly
      (ADP-ribose) polymerase (PARP) fragmentation. Failing SHR had a 7-fold diminished
      expression (p<0.01) of LIFR, no changes in gp130, and 1.6-fold increased
      myocardial expression (p<0.01) of CT-1. In cardiomyocytes isolated from non
      failing SHR, recombinant CT-1 inhibited apoptotic and non-apoptotic cell death
      induced by angiotensin II or hydrogen peroxide. LIFR protein was entirely absent
      in cardiomyocytes isolated from failing SHR, which were resistant to the
      cytoprotective effects of CT-1. Finally, stimulation of non-failing SHR
      cardiomyocytes with angiotensin II, aldosterone, norepinephrine or endothelin-1
      significantly decreased (p<0.01) LIFR expression. CONCLUSIONS: These data suggest
      that loss of CT-1-dependent survival mechanisms may contribute to the increase of
      cell death associated with HF in SHR. Neurohumoral activation may contribute to
      this alteration via suppression of LIFR.

PMID- 17559825
TI  - Lutein presents suppressing but not blocking chemopreventive activity during
      diethylnitrosamine-induced hepatocarcinogenesis and this involves inhibition of
      DNA damage.
AB  - Cancer chemopreventive agents are classified as blocking or suppressing agents if
      they inhibit initiation or promotion/progression phase of carcinogenesis,
      respectively. Two experiments were conducted in order to classify lutein as a
      blocking and/or suppressing agent during rat hepatocarcinogenesis. Inhibitory
      effects of lutein on hepatic preneoplastic lesions (PNL) and DNA strand breakage
      induced in Wistar rats by the resistant hepatocyte model of hepatocarcinogenesis
      (initiation with diethylnitrosamine and promotion with 2-acetylaminofluorene
      coupled with partial hepatectomy) were investigated when the carotenoid was
      administered specifically during initiation (experiment 1) or promotion
      (experiment 2) phase. Animals received by gavage during 2 (experiment 1) or six
      (experiment 2) consecutive weeks on alternate days 70 mg/kg body weight of
      lutein. Rats treated with only corn oil during these same periods and submitted
      to this model were used as controls. Treatment with lutein during initiation did
      not inhibit nor induced (P>0.05) hepatic preneoplastic lesions and DNA damage. On
      the other hand, treatment during promotion inhibited (P<0.05) the size of hepatic
      macroscopic nodules and DNA damage and increased (P<0.05) lutein hepatic levels
      that reached levels seen in human liver samples. Lutein presented inhibitory
      actions during promotion but not initiation of hepatocarcinogenesis, being
      classified as a suppressing agent. This reinforces lutein as a potential agent
      for liver cancer chemoprevention.

PMID- 17559826
TI  - 1H NMR investigation on interaction between ibuprofen and lipoproteins.
AB  - A large number of studies indicate that oxidative modification of plasma
      lipoproteins, especially low-density lipoprotein (LDL), is a critical factor in
      initiation and progression of atherosclerosis. We have previously found that
      ibuprofen (IBP), a potential antioxidant drug to inhibit LDL oxidation,
      interacted with lipoproteins in intact human plasma. In the present study, we
      compare the binding affinities of IBP to LDL and HDL (high-density lipoprotein)
      by (1)H NMR spectroscopy. When IBP is added into the HDL and LDL samples, the -
      N(+)(CH(3))(3) moieties of phosphatidylcholine (PC) and sphingomyelin (SM) in
      lipoprotein particles experience the chemical shift up-field drift.
      Intermolecular cross-peaks observed in NOESY spectra imply that there are direct
      interactions between ibuprofen and lipoproteins at both hydrophobic and
      hydrophilic (ionic) regions. These interactions are likely to be important in the
      solubility of ibuprofen into lipoprotein particles. Ibuprofen has higher impact
      on the PC and SM head group ( - N(+)(CH(3))(3)) and - (CH(2))(n) - group in HDL
      than that in LDL. This could be explained by either IBP has higher binding
      affinity to HDL than to LDL, or IBP induces orientation of the phospholipid head
      group at the surface of the lipoprotein particles.

PMID- 17559827
TI  - Ol-insm1b, a SNAG family transcription factor involved in cell cycle arrest
      during medaka development.
AB  - Through whole-mount in situ hybridisation screen on medaka (Oryzias latipes)
      brain, Ol-insm1b, a member of the Insm1/Mlt1 subfamily of SNAG-domain containing
      genes, has been isolated. It is strongly expressed during neurogenesis and
      pancreas organogenesis, with a pattern that suggests a role in cell cycle exit.
      Here, we describe Ol-insm1b expression pattern throughout development and in
      adult brain, and we report on its functional characterisation. Our data point to
      a previously unravelled role for Ol-insm1b as a down-regulator of cell
      proliferation during development, as it slows down the cycle without triggering
      apoptosis. Clonal analysis demonstrates that this effect is cell-autonomous, and,
      through molecular dissection studies, we demonstrate that it is likely to be non
      transcriptional, albeit mediated by zinc-finger domains. Additionally, we report
      that Ol-insm1b mRNA, when injected in one cell of two-cell stage embryos,
      exhibits a surprising behaviour: it does not spread uniformly amongst daughter
      cells but remains cytoplasmically localised in the progeny of the injected
      blastomere. Our experiments suggest that Insm1 is a negative regulator of cell
      proliferation, possibly through mechanisms that do not involve modulation of
      transcription.

PMID- 17559828
TI  - Suppression of Hedgehog signaling by Cul3 ligases in proliferation control of
      retinal precursors.
AB  - Cullin-RING ubiquitin ligases ubiquitinate protein substrates and control their
      levels through degradation. Here we show that cullin3 (Cul3) suppresses Hedgehog
      (Hh) signaling through downregulating the level of the signaling pathway effector
      cubitus interruptus (Ci). High-level Hh signaling promotes Cul3-dependent Ci
      degradation, leading to the downregulation of Hh signaling. This process is
      manifested in controlling cell proliferation during Drosophila retinal
      development. In Cul3 mutants, the population of interommatidial cells is
      increased, which can be mimicked by overexpression of Ci and suppressed by
      depleting endogenous Ci. Hh also regulates the population of interommatidial
      cells in the pupal stage. Alterations in the interommatidial cell population
      correlate with alterations in precursor proliferation in the second mitotic wave
      of larval eye discs. Taken together, these results suggest that Cul3
      downregulates Ci levels to modulate Hh signaling activity, thus ensuring proper
      cell proliferation during retinal development.

PMID- 17559829
TI  - SCL-GFP transgenic zebrafish: in vivo imaging of blood and endothelial
      development and identification of the initial site of definitive hematopoiesis.
AB  - The bHLH transcription factor SCL plays a central role in the generation of
      hematopoietic cells in vertebrates. We modified a PAC containing the whole
      zebrafish scl locus, inserting GFP into the first coding exon of scl. In germline
      transgenic zebrafish generated using this construct, GFP expression completely
      recapitulates the endogenous expression of scl in blood, endothelium and CNS. We
      performed in vivo timelapse imaging of blood and endothelial precursor migration
      at the single-cell level and show that these cells migrate from the posterior
      lateral plate mesoderm to their site of differentiation in the intermediate cell
      mass. The anterior lateral plate domain of GFP expression gives rise to primitive
      macrophages and the blood vessels of the head. In later embryos, GFP expression
      identifies clusters of hematopoietic cells that develop between the dorsal aorta
      and posterior cardinal veins after primitive erythrocytes have entered
      circulation. Two treatments that block definitive hematopoiesis (treatment with
      dioxin (TCDD), and injection of an antisense morpholino oligonucleotide targeted
      to runx1) ablate these hematopoietic clusters. This indicates that these clusters
      represent the first site of definitive hematopoiesis in zebrafish. This site is
      anatomically homologous to the proposed source of hematopoietic stem cells in
      amniotes, the aorta-gonad-mesonephros (AGM) region. A second transgenic line,
      containing the promoter of scl driving GFP, lacks expression in the definitive
      clusters.

PMID- 17559830
TI  - Developmental acquisition of genome-wide DNA methylation occurs prior to meiosis
      in male germ cells.
AB  - The development of germ cells is a highly ordered process that begins during
      fetal growth and is completed in the adult. Epigenetic modifications that occur
      in germ cells are important for germ cell function and for post-fertilization
      embryonic development. We have previously shown that male germ cells in the adult
      mouse have a highly distinct epigenetic state, as revealed by a unique genome
      wide pattern of DNA methylation. Although it is known that these patterns begin
      to be established during fetal life, it is not known to what extent DNA
      methylation is modified during spermatogenesis. We have used restriction landmark
      genomic scanning (RLGS) and other techniques to examine DNA methylation at
      multiple sites across the genome during postnatal germ cell development in the
      mouse. Although a significant proportion of the distinct germ cell pattern is
      acquired prior to the type A spermatogonial stage, we find that both de novo
      methylation and demethylation occur during spermatogenesis, mainly in
      spermatogonia and spermatocytes in early meiotic prophase I. Alterations include
      predominantly non-CpG island sequences from both unique loci and repetitive
      elements. These modifications are progressive and are almost exclusively
      completed by the end of the pachytene spermatocyte stage. These studies better
      define the developmental timing of genome-wide DNA methylation pattern
      acquisition during male germ cell development.

PMID- 17559831
TI  - Immediate and one-year post-intervention effectiveness of Maryland's lead law
      treatments.
AB  - A 1994 Maryland law prescribes a lead-based paint risk reduction standard for pre
      1950, privately owned rental housing. This standard, applied at each tenancy
      change, can be met by sampling to verify that dust lead loadings are within
      acceptable limits or by performing specific lead hazard reduction treatments,
      followed by an independent visual inspection without dust sampling. We evaluated
      the ability of visual inspection to predict treatment completion and dust lead
      loadings. Fifty-two Baltimore housing units were enrolled and received the law
      specified treatments. Before treatment, study risk assessors conducted visual
      assessments and dust lead wipe sampling in each unit. After treatment, Maryland
      certified visual inspectors conducted the law's required visual inspection,
      followed by the study risk assessors, who performed a separate visual assessment
      and collected dust wipe samples. One year later, study risk assessors performed
      another visual assessment and dust wipe sampling (n=34). Dust lead loadings
      declined significantly immediately after prescribed lead treatments were
      implemented. Fifty-three percent, 20%, and 47% of units had at least one sample
      that exceeded 1995 EPA/HUD floor, window sill and window trough clearance
      guidance of 100, 500 and 800 microg/ft2, respectively. Overall, 73% of units had
      one or more immediate post-intervention single surface sample results exceeding
      the 1995 clearance values that were in effect at the time of the study. One-year
      post-intervention loadings remained significantly below pre-intervention levels
      for floors but not window sills or troughs. Visual assessments alone, without
      dust lead testing, did not ensure that prescribed treatments were completed or
      that dust lead loadings were below clearance values.

PMID- 17559832
TI  - Influence of cisplatin-induced renal failure on the alpha(1)-adrenoceptor subtype
      causing vasoconstriction in the kidney of the rat.
AB  - This study investigated whether the alpha(1)-adrenoceptor subtype(s) mediating
      the vasoconstrictor actions of the renal sympathetic nerves were altered in rats
      with cisplatin-induced renal failure. Male Wistar Kyoto rats were used and half
      received cisplatin (5 mg/kg i.p.) to induce renal failure and were taken for
      study 7 days later. The renal blood flow reductions caused by electrical renal
      nerve stimulation and close intra-renal administration of noradrenaline,
      phenylephrine and methoxamine were determined before and after amlodopine (AMP),
      5-methylurapidil (MeU), chloroethylclonidine (CEC) or BMY 7378. Water intake and
      creatinine clearance were decreased (P<0.05) by 40-50% while fractional excretion
      of sodium was increased two-fold in the cisplatin treated rats. Mean arterial
      pressure was higher, 110+/-2 versus 102+/-3 mmHg and renal blood flow was lower,
      10.7+/-0.9 versus 18.9+/-0.1 ml/min/kg in the renal failure rats (both P<0.05).
      AMP, MeU and BMY 7378 decreased (all P<0.05) the adrenergically induced renal
      vasoconstrictor responses in the renal failure groups by 30 to 50% and in normal
      rats by 20 to 40%. In the presence of CEC, renal nerve stimulation and
      noradrenaline and methoxamine induced renal vasoconstrictor responses were
      enhanced (all P<0.05) in the renal failure but not in the normal rats. These data
      showed that alpha(1A)- and alpha(1D)-adrenoceptors were the major subtypes in
      mediating adrenergically induced renal vasoconstriction but there was no
      substantial shift in subtype in renal failure. The contribution of alpha(1B)
      adrenoceptor subtypes either pre- or post-synaptic appeared to be raised in the
      renal failure rats.

PMID- 17559833
TI  - Anti-inflammatory effects of compounds alpha-humulene and (-)-trans-caryophyllene
      isolated from the essential oil of Cordia verbenacea.
AB  - This study evaluated the anti-inflammatory properties of two sesquiterpenes
      isolated from Cordia verbenacea's essential oil, alpha-humulene and (-)-trans
      caryophyllene. Our results revealed that oral treatment with both compounds
      displayed marked inhibitory effects in different inflammatory experimental models
      in mice and rats. alpha-humulene and (-)-trans-caryophyllene were effective in
      reducing platelet activating factor-, bradykinin- and ovoalbumin-induced mouse
      paw oedema, while only alpha-humulene was able to diminish the oedema formation
      caused by histamine injection. Also, both compounds had important inhibitory
      effects on the mouse and rat carrageenan-induced paw oedema. Systemic treatment
      with alpha-humulene largely prevented both tumor necrosis factor-alpha (TNFalpha)
      and interleukin-1beta (IL-1beta) generation in carrageenan-injected rats, whereas
      (-)-trans-caryophyllene diminished only TNFalpha release. Furthermore, both
      compounds reduced the production of prostaglandin E(2) (PGE(2)), as well as
      inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX-2) expression,
      induced by the intraplantar injection of carrageenan in rats. The anti
      inflammatory effects of alpha-humulene and (-)-trans-caryophyllene were
      comparable to those observed in dexamethasone-treated animals, used as positive
      control drug. All these findings indicate that alpha-humulene and (-)-trans
      caryophyllene, derived from the essential oil of C. verbenacea, might represent
      important tools for the management and/or treatment of inflammatory diseases.

PMID- 17559834
TI  - Endothelial gap junctions are down-regulated by arsenic trioxide.
AB  - We investigated the effect of As(2)O(3), an anti-cancer drug, on endothelial gap
      junctions. Human aortic endothelial cells (HAEC) were treated with As(2)O(3) at
      1, 10, 100, and 1000 ng/ml and the cells were examined to evaluate the expression
      of connexin43 (Cx43) and to assess gap-junction communication. Endothelial nitric
      oxide synthase (eNOS) and nitric oxide (NO) were measured to assess for
      endothelial dysfunction. Male Sprague-Dawley rats were given intravenous
      As(2)O(3) (200 mug/kg/day) or saline for 4 weeks, after which aortic endothelial
      gap junctions, eNOS, and circulating NO levels were evaluated. We found that HAEC
      Cx43 transcripts and gap junctions were reduced and gap-junction communication
      was attenuated by As(2)O(3). This decrease of Cx43 gap junctions was prevented by
      the addition of protease inhibitors. At a dose of 100 ng/ml of As(2)O(3), eNOS
      was reduced at 48 h, but NO was markedly reduced by 1 h. In animals treated with
      As(2)O(3), endothelial gap junctions comprising Cx37, Cx40, or Cx43 were all
      reduced in amount, while eNOS and circulating NO levels remained unchanged. In
      both in vitro and in vivo rat experiments, endothelial gap junctions were
      consistently reduced by As(2)O(3), unlike the response of eNOS and NO, which were
      decreased in cells but not in the rat aortic endothelium. The reduction in Cx43
      involved both down-regulation at the transcriptional level and increased
      degradation. These findings indicate that gap-junction communication in the
      vascular endothelium is inhibited by treatment with As(2)O(3).

PMID- 17559835
TI  - Carvedilol ameliorates endothelial dysfunction in streptozotocin-induced diabetic
      rats.
AB  - The beta-blocker, carvedilol has an additional endothelium-dependent vasodilating
      properties in patients with hypertension or heart failure. Whether carvedilol can
      improve endothelium-dependent relaxation in a diabetic animal model and its
      mechanism of action are unknown. The aim of this study was to investigate the
      effect of carvedilol on the endothelial-response of aortas from diabetic rats and
      the underlying mechanism. Acetylcholine-induced endothelium-dependent relaxation,
      sodium nitroprusside (SNP)-induced endothelium-independent relaxation, and
      expression of nitric oxide synthase 3 (NOS3) mRNA were measured in aortas
      isolated from both non-diabetic and streptozotocin-induced diabetic rats. The
      level of NO in serum was also measured 5 weeks after carvedilol administration (1
      or 10 mg/kg/day). Endothelium-dependent relaxation declined along with the
      decrease of serum NO level in aortas from diabetic rats. Treatment with
      carvedilol for 5 weeks prevented the inhibition of endothelium-dependent
      relaxation and the decrease of serum NO levels caused by diabetes. The expression
      of NOS3 mRNA, protein expression and NOS3 phosphorylation at Ser1177 in diabetic
      rat aorta was very low in untreated diabetic aortas compared with the healthy
      group. Administration of carvedilol not only significantly increased the
      expression of NOS3 mRNA but also protein expression and NOS3 phosphorylation at
      Ser1177 in the healthy and diabetic groups. In conclusion, chronic carvedilol
      administration significantly ameliorated the endothelial dysfunction in diabetic
      rat aortas, in which increased NO level, up-regulated NOS3 mRNA and
      phosphorylation at Ser1177 may be involved.

PMID- 17559836
TI  - Phosphomimetic mutation of the mitotically phosphorylated serine 1880 compromises
      the interaction of the transmembrane nucleoporin gp210 with the nuclear pore
      complex.
AB  - The nuclear pore complexes (NPCs) reversibly disassemble and reassemble during
      mitosis. Disassembly of the NPC is accompanied by phosphorylation of many
      nucleoporins although the function of this is not clear. It was previously shown
      that in the transmembrane nucleoporin gp210 a single serine residue at position
      1880 is specifically phosphorylated during mitosis. Using amino acid substitution
      combined with live cell imaging, time-lapse microscopy and FRAP, we investigated
      the role of serine 1880 in binding of gp210 to the NPC in vivo. An alanine
      substitution mutant (S1880A) was significantly more dynamic at the NPC compared
      to the wild-type protein, suggesting that serine 1880 is important for binding of
      gp210 to the NPC. Moreover a glutamate substitution (S1880E) closely mimicking
      phosphorylated serine specifically interfered with incorporation of gp210 into
      the NPC and compromised its post-mitotic recruitment to the nuclear envelope of
      daughter nuclei. Our findings are consistent with the idea that mitotic
      phosphorylation acts to dissociate gp210 from the structural elements of the NPC.

PMID- 17559837
TI  - Spinal cord injury in neonates alters respiratory motor output via supraspinal
      mechanisms.
AB  - Upper cervical spinal cord injury (SCI) alters respiratory output and results in
      a blunted respiratory response to pH/CO2. Many SCI studies have concentrated on
      respiratory changes in neural function caudal to injury; however few have
      examined whether neural plasticity occurs rostral to SCI. Golder et al. (2001a)
      showed that supraspinal changes occur to alter respiratory output after SCI.
      Furthermore, Brown et al. (2004) showed that neural receptors change rostral to a
      thoracic SCI. We hypothesized that SCI in neonates will alter supraspinal output,
      show a blunted response to pH and alter receptor protein levels in the medulla.
      On postnatal day 0/1, a C2 SCI surgery was performed. Two days later, neonates
      were anesthetized and brainstem-spinal cords removed. Respiratory-related
      activity was recorded using the in vitro brainstem-spinal cord preparation and
      the superfusate pH was changed (pH 7.2, 7.4 and 7.8). The respiratory-like
      frequency was significantly reduced in SCI rats indicating supraspinal
      plasticity. Increasing the pH decreased respiratory-like frequency and peak
      amplitude in injured and sham controls. Increasing the pH increased burst
      duration and area in sham controls, whereas in injured rats, the burst duration
      and area decreased. Western blot analysis demonstrated significant changes in
      glutamate receptor subunits (NR1, NR2B and GluR2), adenosine receptors (A1, A2A),
      glutamic acid decarboxylase (65) and neurokinin-1 receptors in medullary tissue
      ipsilateral and contralateral to injury. These data show that supraspinal
      plasticity in the respiratory system occurs after SCI in neonate rats. The
      mechanisms remain unknown, but may involve alterations in receptor proteins
      involved in neurotransmission.

PMID- 17559838
TI  - Ammonia channeling in bacterial glucosamine-6-phosphate synthase (Glms):
      molecular dynamics simulations and kinetic studies of protein mutants.
AB  - Ammonia transfer from the glutamine site to the fructose-6P site of bacterial
      glucosamine-6-phosphate synthase was studied by molecular dynamics simulations.
      The studies suggest a key role for Trp74, in the sealing of the hydrophobic
      channel connecting the two binding sites, as well as for the two Ala602 and
      Val605 residues, which form a narrow passage whose opening/closing constitutes an
      essential event in ammonia transfer. Kinetic analyses of the corresponding
      protein mutants confirmed our predictions. The efficiency of ammonia transfer
      which was close to zero in the W74A mutant was partially restored by increasing
      the size of the corresponding side-chain; the simulations performed on the W74A
      mutant suggested the formation of a hole in the channel. In the case of A602L and
      V605L mutants, the efficiency of ammonia transfer decreased to approximately 50%
      of the value of the native protein. None of the mutants were, however, able to
      use exogenous ammonia as a substrate.

PMID- 17559839
TI  - Effects of pH and salt concentration on the siRNA binding activity of the RNA
      silencing suppressor protein p19.
AB  - The RNA silencing pathway is an important component of the anti-viral immune
      response in eukaryotes, particularly in plants. In turn, many viruses have
      evolved mechanisms to evade or suppress this pathway. Tombusviruses such as the
      Carnation Italian ringspot virus (CIRV) express a 19kDa protein (p19) that is a
      suppressor of RNA silencing in infected plants. This protein acts as a dimer and
      binds specifically to short-interfering RNA (siRNA) through electrostatic
      interactions between charged residues in the binding cleft. Since pH and salt
      concentrations can vary widely from host to host, we have investigated the
      influence of these parameters on the siRNA binding activity of CIRV p19.
      Previously, we established a convenient fluorescence-based method for assaying
      CIRV p19:siRNA binding using Ni(2+)-NTA coated 96-well plates. Using this method,
      we observe that the CIRV p19 protein binds to siRNA with nanomolar affinity and
      that this binding is sensitive to pH and salt concentration. The pH-dissociation
      constant profile shows that CIRV p19:siRNA binding is dependent on three
      different apparent pK(a) values. The values extrapolated from the curve are 7.1,
      8.0 and 10.6 that we interpret as the ionization of one or more histidine,
      cysteine and lysine residues, respectively. We find that the optimal suppression
      of RNA silencing by CIRV p19 occurs in the pH range from 6.2 to 7.6.

PMID- 17559840
TI  - Inhibitors of the heat shock response: biology and pharmacology.
AB  - A number of human diseases can be linked to aberrations in protein folding which
      cause an imbalance in protein homeostasis. Molecular chaperones, including heat
      shock proteins, act to assist protein folding, stability and activity in the
      cell. Attention has begun to focus on modulating the expression and/or activity
      of this group of proteins for the treatment of a wide variety of human diseases.
      This review will describe the progress made to date in developing pharmacological
      modulators of the heat shock response, including both agents which affect the
      entire heat shock response and those that specifically target the HSP70 and HSP90
      chaperone families.

PMID- 17559841
TI  - Impairment in a negative regulatory system for TCR signaling in CD4+ T cells from
      old mice.
AB  - To examine the involvement of lipid rafts in an age-associated decline in T cell
      function, we analyzed the effect of aging on the constituents of lipid rafts in
      resting mouse CD4(+) T cells. We found a pronounced, age-dependent reduction in
      PAG/Cbp, which is involved in the regulation of Src family kinases (SFKs) by
      recruiting Csk (a negative regulator of SFKs) to lipid rafts. This reduction is
      specific for T cells and is attributed, at least in part, to the reduction in its
      mRNA level. The reduction of PAG accompanies marked impairment in recruiting Csk
      to lipid rafts and a concomitant decrease in the inactive forms of SFKs. These
      findings indicate that old mouse CD4(+) T cells have a defect in a negative SFK
      regulatory system.

PMID- 17559842
TI  - Mullerian Inhibiting Substance is an ovarian growth factor of emerging clinical
      significance.
AB  - OBJECTIVE: To examine Mullerian Inhibiting Substance (MIS) as an emerging
      diagnostic marker of ovarian function. DESIGN: Medline review of published
      studies pertaining to the role of MIS in assessing ovarian aging, predicting
      response to ovulation induction in preparation for in vitro fertilization,
      assessing risk of developing ovarian hyperstimulation (OHSS) before ovulation
      induction, and diagnosis of polycystic ovarian disease (PCOS). RESULT(S): The
      majority of published studies to date support a role for MIS as a marker of
      ovarian reserve. Specific cut-off values are dependent upon the particular assay
      used. Mullerian Inhibiting Substance may offer value in assessing risk of OHSS
      and diagnosis of PCOS. CONCLUSION(S): Potential advantages of MIS compared with
      other conventional markers of ovarian reserve include: 1) MIS is the earliest
      marker to change with age; 2) it has the least intercycle variability; 3) it has
      the least intracycle variability; and 4) it may be informative if randomly
      obtained during the cycle. Widespread clinical use of MIS may await the
      availability of an international standard for MIS so that results using different
      assays may be reliably compared.

PMID- 17559843
TI  - Stimulation of endometrium embryo transfer (SEET): injection of embryo culture
      supernatant into the uterine cavity before blastocyst transfer can improve
      implantation and pregnancy rates.
AB  - OBJECTIVE: To evaluate whether stimulation of endometrium embryo transfer (SEET)
      by injecting embryo culture supernatant (ECS) into the uterus before blastocyst
      transfer (BT) can improve implantation and pregnancy rates. DESIGN: Randomized,
      controlled trial. SETTING: Private in vitro fertilization clinic. PATIENT(S): 23
      women in the SEET group, and 25 women in the control group. INTERVENTION(S):
      Injection of ECS. MAIN OUTCOME MEASURE(S): Implantation rates, pregnancy rates,
      and serum beta human chorionic gonadotropin (beta-hCG) levels at 4 weeks and 1
      day of gestation. RESULT(S): Communication between the embryo and the endometrium
      (cross-talk) plays an important role in implantation. Several embryonic factors
      that modulate endometrial receptivity have been detected in ECS. In BT, cross
      talk is absent until the blastocysts are transferred, so we injected ECS into the
      uterine cavity before BT to stimulate the endometrium and provide an optimum
      environment for implantation of forthcoming blastocysts. The implantation rates,
      pregnancy rates, and beta-hCG levels in the SEET group were statistically
      significantly higher than those in the BT control group. CONCLUSION(S): A novel
      method of embryo transfer based on the concept of embryo-dependent induction of
      endometrial receptivity, SEET may be an effective option for increasing
      implantation and pregnancy rates.

PMID- 17559844
TI  - Role of insulin in the hyperandrogenemia of lean women with polycystic ovary
      syndrome and normal insulin sensitivity.
AB  - OBJECTIVE: To determine the effect of reducing insulin secretion on
      hyperandrogenemia in lean normoinsulinemic women with polycystic ovary syndrome
      (PCOS) and normal metabolic insulin sensitivity. DESIGN: Transversal assessment
      at baseline and prospective follow-up of lean PCOS group after 8 days of
      diazoxide, which reduces insulin secretion, and 1 month of leuprolide, which
      suppresses LH. SETTING: Clinical research center of an academic hospital.
      PATIENT(S): Nine lean women (body mass index <or=25 kg/m(2)) with PCOS and normal
      insulin levels, as well as 17 lean healthy women. INTERVENTION(S): Lean PCOS
      women were reassessed after 8 days of diazoxide and after 1 month of leuprolide,
      which suppresses LH. MAIN OUTCOME MEASURE(S): Androgen levels and insulin
      stimulated glucose disposal (metabolic insulin sensitivity), determined by
      euglycemic-hyperinsulinemic clamp (M-value). RESULT(S): Mean M-value of lean PCOS
      women (48.5 micromol/kg.min) was similar to lean control subjects (52.9
      micromol/kg.min). They also had comparable anthropometric measures, lipids,
      fibrinogen, and plasminogen activator inhibitor 1. The LH did not change
      significantly after diazoxide, but was almost suppressed after leuprolide in the
      PCOS group. Androstenedione decreased significantly after diazoxide and even more
      after leuprolide. However, free T significantly decreased only after diazoxide in
      lean PCOS women. Diazoxide also increased SHBG significantly in this group.
      CONCLUSION(S): In women with typical PCOS and normal insulin levels and metabolic
      insulin sensitivity, reducing insulin secretion significantly decreased androgen
      and increased SHBG levels. These results suggest that insulin contributes to
      hyperandrogenemia even in PCOS women with normal metabolic insulin sensitivity,
      which might be due to increased sensitivity of their androgenic insulin pathway.

PMID- 17559845
TI  - Among women undergoing embryo transfer, is the probability of pregnancy and live
      birth improved with ultrasound guidance over clinical touch alone? A systemic
      review and meta-analysis of prospective randomized trials.
AB  - OBJECTIVE: To investigate the theory that ultrasound guidance during ET improves
      clinical outcomes. DESIGN: Systematic review of prospective, randomized,
      controlled trials comparing ultrasound with clinical touch methods of embryo
      catheter guidance. SETTING: Infertility centers. PATIENT(S): 5,968 ET cycles in
      women. INTERVENTION(S): Embryo transfer with or without ultrasound guidance. MAIN
      OUTCOME MEASURE(S): Meticulous electronic (e.g., PubMed, EMBASE, CENTRAL) and
      hand searches were performed to locate trials. Primary outcome measures were the
      live-birth, ongoing pregnancy, and clinical pregnancy rates. Secondary outcome
      measures were the implantation, multiple pregnancies, and miscarriage rates. In
      addition, the incidences of ectopic pregnancies and difficult transfers were
      evaluated. RESULT(S): Twenty-five studies were retrieved, of which five were
      excluded. Meta-analysis of the remaining studies (5,968 ET cycles in women) was
      conducted by using the Mantel-Haenszel method (fixed-effect model). There was a
      significantly increased chance of a live birth (odds ratio [OR] = 1.78, 95%
      confidence interval [CI] = 1.19 to 2.67), ongoing pregnancy (OR = 1.51, 95% CI =
      1.31 to 1.74), clinical pregnancy (OR = 1.50, 95% CI = 1.34 to 1.67), embryo
      implantation (OR = 1.35, 95% CI = 1.22 to 1.50), and easy transfer rates after
      ultrasound guidance (OR = 0.68, 95% CI = 0.58 to 0.81). There was no difference
      in multiple pregnancy, ectopic pregnancy, or miscarriage rates. CONCLUSION(S):
      Ultrasound-guided ET significantly increases the chance of live birth and ongoing
      and clinical pregnancy rates compared with the clinical touch method.

PMID- 17559846
TI  - Genistein causes regression of endometriotic implants in the rat model.
AB  - OBJECTIVE: To determine the effects of raloxifene and genistein on experimentally
      induced endometriosis in a rat model. DESIGN: Prospective, randomized animal
      study. SETTING: Animal surgery laboratory in a university hospital. ANIMAL(S):
      Thirty-three adult, mature female Wistar-Albino rats in which endometriotic
      implants were induced by transplanting autologous uterine tissue to ectopic sites
      on the peritoneum. INTERVENTION(S): After the endometriotic implants were formed
      surgically, the 33 rats were randomly divided into three groups. Group 1
      (genistein group, 10 rats) were given 500 mg/kg per day of oral genistein. Group
      2 (raloxifene group, 10 rats) were given 10 mg/kg per day of oral raloxifene.
      Group 3 were given no medication and served as controls (13 rats). All the rats
      continued to receive treatment for 21 days, and then were killed to assess the
      implants' size and for histologic examination. MAIN OUTCOME MEASURE(S): The
      surface area of the endometriotic implants and the score of histologic analysis.
      RESULT(S): At the beginning of the medical treatment, the mean surface areas of
      the endometriotic implants were comparable in all three groups. At the end of the
      medical treatment, the mean surface area of implants in groups 1 and 2 was
      smaller than that of implants in the control group. The decrease in the surface
      area of the endometriotic implants was greater in group 1 and group 2 than found
      in the control group. The histologic assessment revealed that the mean of the
      histopathologic score of the implants at the end of the treatment was lower in
      groups 1 and 2 when compared with the control group. CONCLUSION(S): Genistein
      caused a statistically significant regression of endometriotic implants.

PMID- 17559847
TI  - The contribution of genetic variations of aryl hydrocarbon receptor pathway genes
      to male factor infertility.
AB  - OBJECTIVE: To determine whether the polymorphisms in aryl hydrocarbon receptor
      (AHR), aryl hydrocarbon receptor repressor (AHRR), and aryl hydrocarbon receptor
      nuclear translocator (ARNT) genes are associated with male factor infertility.
      DESIGN: An association study. SETTING: University research laboratory and
      andrology clinic. PATIENT(S): The subjects were infertile Estonian men (n = 112)
      with azoospermia or oligozoospermia and controls (n = 212) with normal sperm
      parameters. INTERVENTION(S): Blood samples were obtained for DNA extraction and
      genotyping. MAIN OUTCOME MEASURE(S): AHR (Arg554Lys), AHRR (Pro185Ala), and ARNT
      (G/C allele) polymorphisms were genotyped using allele-specific polymerase chain
      reaction. Allele and genotype frequencies were compared between infertile men and
      controls and separately in the normozoospermia, oligozoospermia, and azoospermia
      groups. RESULT(S): The AHRR Ala185Ala genotype was implicated in susceptibility
      to male factor infertility. Ala/Ala genotype frequency increased in the following
      order: normozoospermia (18.0%), oligozoospermia (26.0%), azoospermia (42.1%).
      Allele and genotype frequencies of AHR and ARNT polymorphisms were similar
      between cases and controls. CONCLUSION(S): We demonstrated that the AHRR
      Pro185Ala polymorphism contributed to a predisposition to male factor infertility
      in the Estonian population. A greater prevalence of the Ala/Ala genotype was
      found among infertile patients.

PMID- 17559848
TI  - Preliminary analysis of the G178A polymorphism of insulin-like factor 3 in male
      infertility.
AB  - We investigated the association of nonsynonymous insulin-like factor 3 (INSL3)
      G178A polymorphism with nonobstructive male infertility. The common INSL3 G178A
      polymorphism was not statistically significantly associated with male infertility
      (P>.05), even though INSL3 is essential for the occurrence of bilateral
      cryptorchidism.

PMID- 17559849
TI  - Neuropeptides of the islets of Langerhans: a peptidomics study.
AB  - Neuropeptides from the endocrine pancreas (the islets of Langerhans) play an
      important role in the regulation of blood glucose levels. Therefore, our aim is
      to identify the "peptidome" (the in vivo peptide profile at a certain time) of
      the pancreatic islets, which is beneficial for medical progress related to the
      treatment of diabetes. So far, there are few neuropeptides isolated and sequenced
      from the endocrine pancreas and mainly in situ hybridisation and
      immunocytochemical techniques have been used to demonstrate the occurrence of
      peptides in the pancreas. These techniques do not allow for unequivocal
      identification of peptides. In contrary, mass spectrometry identifies peptides
      unambiguously. We have analysed the peptidome of the islets using peptidomics,
      i.e. a combination of liquid chromatography, mass spectrometry and
      bioinformatics. We are able to identify the peptidome of islets extracts. We not
      only confirm the presence of peptides with a well-known effect on blood glucose
      levels, but also identify new peptides, which are unknown to affect blood glucose
      levels.

PMID- 17559850
TI  - Insulin-like peptides in Spodoptera littoralis (Lepidoptera): Detection,
      localization and identification.
AB  - Insulin is an extensively studied peptide hormone in mammals. However, insulin is
      not restricted to vertebrates, but has also been identified in invertebrates,
      among whom several insect species. These insulin-like peptides (ILPs) show
      structural and-at least some-functional homology with mammalian insulin and act
      through a conserved pathway. Yet many aspects of insulin function in insects
      remain to be unveiled. We analyzed the presence of ILPs in the cotton leafworm,
      Spodoptera littoralis, at two levels: (1) cellular localization of ILPs in whole
      tissues of the central nervous system from S. littoralis, and (2) detection and
      identification of ILPs at nucleotide level. To our knowledge, nothing about the
      presence of ILPs in S. littoralis has been described so far. By whole mount in
      situ immunolocalization, we localized bombyxin-like material in S. littoralis in
      four pairs of pars intercerebralis cells and in the corpus cardiacum-corpus
      allatum complexes. In addition, we have cloned two different S. littoralis ILP
      precursor cDNAs by a combination of PCR and RAcE. The corresponding precursor
      polypeptides ('Sl-ILPP1' and 'Sl-ILPP2') show significant sequence homology with
      precursors for bombyxin and other bombyxin-related peptides. Our results strongly
      suggest that the S. littoralis ILPs belong to the category of bombyxin-analogs.

PMID- 17559851
TI  - Cloning of sole proopiomelanocortin (POMC) cDNA and the effects of stocking
      density on POMC mRNA and growth rate in sole, Solea solea.
AB  - Proopiomelanocortin (POMC) is an important gene implicated in different
      functions, such as the stress response of the hypothalamus-pituitary-adrenal
      axis. The aim of the present study was to determine whether farming conditions,
      such as stocking density, can be considered a powerful stressor influencing in
      turn the growth rate in juvenile fish. Thus, POMC cDNA expression was
      investigated during adaptation to farming conditions in sole (Solea solea), as a
      model for studying the effects of rearing densities on stress response; different
      stocking densities (50, 100, and 250 animals/m(2)) were applied and, after 7 and
      21 days, the fishes were examined for body weight and plasma cortisol levels as
      indicators of stress. In addition, proopiomelanocortin was cloned and sequenced
      from the brain of sole, allowing semi-quantitative RT-PCR to be performed to
      evaluate POMC mRNA expression in brain tissue. There was a significant increase
      in cortisol levels in fish reared at high stocking densities of 250/m(2) compared
      to fish reared at control densities of 100 and 50/m(2), in both experimental
      times, i.e., 7 and 21 days. The high stocking densities were also found to
      decrease the specific growth rate of fish. Moreover, it was demonstrated that the
      highest stocking density induced a significant decrease in sole POMC mRNA
      expression. It is concluded that POMC and cortisol are both involved in the
      stress response due to high rearing densities, during which cortisol may serve as
      a negative regulator of POMC.

PMID- 17559852
TI  - Raised salivary testosterone in women is associated with increased attraction to
      masculine faces.
AB  - Women's preferences for masculinity in men's faces, voices and behavioral
      displays change during the menstrual cycle and are strongest around ovulation.
      While previous findings suggest that change in progesterone level is an important
      hormonal mechanism for such variation, it is likely that changes in the levels of
      other hormones will also contribute to cyclic variation in masculinity
      preferences. Here we compared women's preferences for masculine faces at two
      points in the menstrual cycle where women differed in salivary testosterone, but
      not in salivary progesterone or estrogen. Preferences for masculinity were
      strongest when women's testosterone levels were relatively high. Our findings
      complement those from previous studies that show systematic variation in
      masculinity preferences during the menstrual cycle and suggest that change in
      testosterone level may play an important role in cyclic shifts in women's
      preferences for masculine traits.

PMID- 17559853
TI  - Oxytocin, water intake, and food sodium availability in male rats.
AB  - This study examined the effect of subcutaneous administration of the neurohormone
      oxytocin on water intake of ad lib-fed (with or without sodium availability in
      the diet) and food-deprived animals. Results of the first experiment showed that
      oxytocin increased water intake and urine excretion in food-deprived but not in
      ad lib-fed animals. However, oxytocin treatment did not modify the reduced water
      "balance" (fluid intake minus urine volume) resulting from food deprivation or
      the daily food intake (Experiment 1). The dose-dependent polydipsic effect of
      oxytocin on food-deprived rats was always preceded by an increase in sodium and
      fluid urine excretion (Experiment 2). Oxytocin also increased the water intake of
      animals fed ad lib with a low sodium diet (Experiment 3). These results suggest
      that the effect of oxytocin on water intake is dependent on the presence or
      absence of sodium in the diet and that the excretion of sodium is the main
      mechanism of oxytocinergic polydipsia in food-deprived male rats.

PMID- 17559854
TI  - Diagnosis of delay-deadline failures in real time discrete event models.
AB  - In this paper a method for fault detection and diagnosis (FDD) of real time
      systems has been developed. A modeling framework termed as real time discrete
      event system (RTDES) model is presented and a mechanism for FDD of the same has
      been developed. The use of RTDES framework for FDD is an extension of the works
      reported in the discrete event system (DES) literature, which are based on finite
      state machines (FSM). FDD of RTDES models are suited for real time systems
      because of their capability of representing timing faults leading to failures in
      terms of erroneous delays and deadlines, which FSM-based ones cannot address. The
      concept of measurement restriction of variables is introduced for RTDES and the
      consequent equivalence of states and indistinguishability of transitions have
      been characterized. Faults are modeled in terms of an unmeasurable condition
      variable in the state map. Diagnosability is defined and the procedure of
      constructing a diagnoser is provided. A checkable property of the diagnoser is
      shown to be a necessary and sufficient condition for diagnosability. The
      methodology is illustrated with an example of a hydraulic cylinder.

PMID- 17559855
TI  - Smooth muscle stiffness variation due to external longitudinal oscillations.
AB  - This research focuses on an in vitro investigation of the stiffness changes of
      contracted airway smooth muscles (ASM) subjected to external longitudinal
      oscillations. ASM tissues were dissected from excised pig tracheas and stimulated
      by a chemical stimulus (acetylcholine, 10(-3) M) to produce maximum contractions.
      The tissues were then systematically excited with external oscillations. Various
      frequencies, amplitudes and durations were used in the experiments to determine
      stiffness changes in response to these variations. Force changes were recorded to
      reflect the muscle stiffness changes. Two stiffness definitions were used to
      quantify the results, dynamic stiffness to reflect variations during oscillation
      and static stiffness to reflect the net effect of oscillation. Under isometric
      contractions, these two stiffnesses were determined before, during and after
      oscillations. Incorporating an empirical stiffness equation, a two-dimensional
      finite element model (FEM) was developed to generalize the tissue responses to
      oscillation. The main outcomes from this work are: the dynamic stiffness has the
      tendency to decrease as the frequency and/or amplitude of external oscillation
      increases; the static stiffness has the tendency of decreasing with an increase
      in the frequency and/or amplitude of excitation until it reaches almost a
      constant value for frequencies at and above 25 Hz. The difference in the behavior
      of the dynamic and static stiffness changes may be attributed to the effect of
      elasticity and mass inertia that are involved in the dynamic motion. The findings
      of this research are in agreement with the hypothesis that oscillations exert a
      direct action on the contractile processes by causing an increased rate of actin
      myosin detachments.

PMID- 17559856
TI  - Time-dependent deformations in bone cells exposed to fluid flow in vitro:
      investigating the role of cellular deformation in fluid flow-induced signaling.
AB  - Numerous experiments have shown fluid flow to be a potent stimulator of bone
      cells in vitro, suggesting that fluid flow is an important physical signal in
      bone mechanotransduction. In fluid flow experiments, bone cells are exposed to
      both time-dependent (e.g., oscillating or pulsing) and time-independent (e.g.,
      steady) flow profiles. Interestingly, the signaling response of bone cells shows
      dependence on loading frequency and/or rate that has been postulated to be due to
      viscoelastic behavior. Thus, the objective of this study was to investigate the
      time-dependent deformations of bone cells exposed to fluid flow in vitro.
      Specifically, our goal was to characterize the mechanical response of bone cells
      exposed to oscillatory flow from 0.5 to 2.0 Hz and steady flow, since these flow
      profiles have previously been shown to induce different morphological and
      biochemical responses in vitro. By tracking cell-bound sulfate and collagen
      coated fluorescent beads of varying sizes, we quantified the normalized peak
      deformation (peak displacement normalized by the maximum peak displacement
      observed for all frequencies) and phase lag in bone cells exposed to 1.0 Pa
      oscillating flow at frequencies of 0.5-2.0 Hz. The phase lag was small (3-10
      degrees ) and frequency dependent, while the normalized peak displacements
      decreased as a weak power law of frequency ( approximately f(-0.2)). During
      steady flow, the cells exhibited a nearly instantaneous deformation, followed by
      creep. Our results suggest that while substantial viscous deformation may occur
      during steady flow (compared to oscillating flow at approximately 1 Hz), bone
      cells behave primarily as elastic bodies when exposed to flow at frequencies
      associated with habitual loading.

PMID- 17559857
TI  - Study of pulse transit time oscillations during obstructive sleep apnoea by using
      a distributed model.
AB  - The study of arterial compliance is useful in understanding the geometrical and
      mechanical properties of a systemic arterial tree. Numerous mathematical models
      have shown their potential in relating the physical phenomena in the arterial
      tree to properties of the wall itself. However, limited model is available that
      describes the pulse transit time (PTT) oscillations of a sleeping child during
      tidal breathing and obstructive sleep apnoea (OSA). Data from 20 children (17
      male; aged 6.4 +/- 4.1 yr) whom were recruited for overnight polysomnography
      (PSG) were used. A modified windkessel model with related physiological
      parameters was utilised to describe PTT fluctuations due to the cardiovascular
      system during sleep. Verification with the recorded PSG data showed similar
      trends with the model for both types of respiratory events. For tidal breathing,
      undamped PTT oscillations of 3.89 s were predicted by the model while actual data
      yielded a mean value of 3.72 +/- 0.79 s. Conversely, under-damping PTT responses
      were expected based on the model for OSA. The model estimated a Q factor of 4.23
      and actual mean data were 3.86 +/- 0.64. Hence, the findings herein suggest that
      the proposed model has the potential to illustrate tidal breathing and OSA events
      in sleeping children.

PMID- 17559858
TI  - Multi-residue method for the determination of basic/neutral pharmaceuticals and
      illicit drugs in surface water by solid-phase extraction and ultra performance
      liquid chromatography-positive electrospray ionisation tandem mass spectrometry.
AB  - The paper presents the development and validation of a new multi-residue method
      for the determination of 28 basic/neutral pharmaceuticals (antiepileptics,
      antibacterial drugs, beta-blockers, analgesics, lipid-regulating agents,
      bronchodilators, histamine-2-blockers, anti-inflammatory agents, calcium channel
      blockers, angiotensin-II antagonists and antidepressants) and illicit drugs in
      surface water with the usage of a new technique: ultra performance liquid
      chromatography-positive electrospray tandem mass spectrometry (UPLC-MS/MS). The
      usage of the novel UPLC system with 1.7 microm particle size and 1mm internal
      diameter column allowed for low mobile phase flow rates (0.07 mL min(-1)) and
      short retention times (from 1.3 to 15.5 min) for all compounds analysed. As a
      result, a fast and cost-effective method was developed. SPE with the usage of
      Oasis MCX strong cation-exchange mixed-mode polymeric sorbent was chosen for
      pharmaceuticals extraction from environmental samples. The influence of matrix
      assisted ion suppression and low SPE recovery on the sensitivity of the method
      was studied. The instrumental limits of quantification varied from 0.2 to 10
      microg L(-1). The method limits of quantification were at low nanogram per litre
      levels and ranged from 0.3 to 50 ng L(-1). The instrumental and method intra- and
      inter-day repeatabilities were on average less than 10%. The method was applied
      for the determination of pharmaceuticals in Rivers Taff (UK) and Warta (Poland).
      Fifteen compounds were determined in river water at levels ranging from single
      nanograms to single micrograms per litre.

PMID- 17559859
TI  - On-line enhancement and separation of nanoparticles using capillary
      electrophoresis.
AB  - We describe a rapid, simple, and highly efficient capillary electrophoresis (CE)
      based method for the analysis of nanoparticles (NPs). In this study, we used the
      reversed electrode polarity stacking mode (REPSM) of CE to assess the feasibility
      of enhancing the detection of Au NPs and Au/Ag NPs, optimizing parameters such as
      the length of time for which the REPSM was applied, the concentrations of the
      buffer and the sodium dodecylsulfate (SDS) surfactant, and the pH. Under the
      optimized on-line enhancement conditions [buffer: SDS (40 mM) and 3
      cyclohexylamino-1-propanesulfonic acid (CAPS; 10 mM) at pH 10.0; applied voltage:
      20 kV; REPSM applied for 24s], the detection limits of the Au NPs and Au/Ag NPs
      increased by ca. 30- and 140-fold, respectively. In addition, when the NPs were
      subjected to on-line enhancement and separation by CE using diode array detection
      (DAD), this approach allowed chemical characterization of the NP species. Our
      results suggest that such CE analyses will be useful for accelerating the rates
      of fabrication and characterization of future nanomaterials.

PMID- 17559860
TI  - Chromatographic comparison of bupivacaine imprinted polymers prepared in crushed
      monolith, microsphere, silica-based composite and capillary monolith formats.
AB  - A comprehensive comparison of five chromatographic stationary phases based on
      molecularly imprinted polymers is presented. Efficiency, imprinting factors,
      water compatibility and batch-to-batch reproducibility are discussed for crushed
      monolith, microspheres, two silica-based composites and capillary monoliths, all
      imprinted with the local anaesthetic bupivacaine. Synthesis protocol and
      chromatographic test conditions have been kept fixed within certain limits, in
      order to provide further insight into the strengths and weaknesses of the
      different formats. Excluding microparticles, all formats give satisfactory
      performance, especially in aqueous mobile phases. An assessment of batch-to-batch
      reproducibility in different mobile phases adds further value to this comparison
      study.

PMID- 17559861
TI  - Large-volume sample stacking with polarity switching for the analysis of bacteria
      by capillary electrophoresis with laser-induced fluorescence detection.
AB  - Capillary electrophoresis has been utilized for the rapid analysis of bacteria
      under specific experimental conditions. In this work, a method of large-volume
      sample stacking with polarity switching was evaluated for the analysis of
      bacteria by capillary electrophoresis with laser-induced fluorescence detection
      in order to enhance the detection sensitivity. The results indicated that the
      proposed method is not only effective for the focusing of bacterial cells, but
      also for the separation of mixtures of bacteria. With the optimized conditions,
      an enhancement factor of around 60-fold was obtained when long sample plug (up to
      39.6% of capillary volume) was injected. Moreover, with the help of such stacking
      method, single, sharp, intense peak with high efficiency was observed without
      multiple peaks attributable to irregular clusters and aggregates of bacterial
      cells. This simple stacking approach appears to be promising as a rapid sterility
      test in various fields of applications.

PMID- 17559862
TI  - Preparation and evaluation of hydroxylated poly(glycidyl methacrylate-co-ethylene
      dimethacrylate) monolithic capillary for in-tube solid-phase microextraction
      coupled to high-performance liquid chromatography.
AB  - A hydroxylated poly(glycidyl methacrylate-co-ethylene dimethacrylate) (GMA-co
      EDMA) monolithic capillary was prepared and investigated for in-tube solid-phase
      microextraction (SPME). The polymer monolith was synthesized by in-situ
      polymerization of GMA and EDMA in the presence of dodecanol and toluene as the
      mixed porogenic solvents. After polymerization, glycidyl groups were hydrolyzed
      with sulfuric acid to produce diol groups at the surface of the porous monolith.
      To investigate the extraction mechanism, several groups of model analytes
      (including neutral, acidic and basic) were selected to perform extractions. The
      resulting monolith showed high extraction selectivity towards polar compounds,
      which resulted from the enhancement of dipole-dipole and hydrogen bonding
      interactions relative to hydrophobic interactions. The equilibrium extraction
      time profiles were also monitored for those model compounds to assess the
      extraction capacity of the monolithic capillary. Moreover, the hydroxylated
      poly(GMA-co-EDMA) monolithic capillary exhibited satisfactory reproducibility and
      stability. Finally, the in-tube SPME-HPLC method, based on the developed
      monolithic capillary as the extraction media, was successfully applied to the
      determination of five polar organic contaminants in lake water.

PMID- 17559863
TI  - Microcontact printing of Concanavalin A and its effect on mammalian cell
      morphology.
AB  - In this study a major lectin called Concanavalin A (ConA) has been micropatterned
      on a glass substrate by microcontact printing and the patterns have been
      characterized with fluorescent and atomic force microscope for their uniformity.
      Interaction of the patterns with mammalian cells has been investigated by
      culturing L929 mouse fibroblast cells on the ConA printed glass surface. Cell
      culture results obtained from the microcontact printed patterns have also been
      compared and benchmarked with another patterning technique named micromolding in
      capillaries (MIMIC). It has been revealed that in spite of molecular level
      heterogeneity and agglomeration of protein molecules in microcontact printed
      form, they can still interact with cell surface glycoproteins, impede the
      mobility of membrane receptor which results in altered morphology of the
      fibroblast cells.

PMID- 17559864
TI  - Maturation of mucosal immune responses and influence of maternal antibodies.
AB  - The mucosae represent the primary point of contact between the major respiratory
      and enteric pathogens and the innate and adaptive immune response. The
      microanatomy and function of the mucosal immune system is now well-characterized,
      in particular the major effector mechanism that involves the production and
      translocation of secretory immunoglobulin A (IgA). Mucosal delivery of antigen
      has the potential to induce potent local and systemic immunity, although such
      responses may differ between neonatal, infant and adult mice. In younger animals
      mucosal immune responses are Th2 biased, whereas in adults there is a broader Th1
      and Th2 responsiveness. There is much interest in the development of mucosally
      delivered vaccines which can be tailored to enhance Th1 immunity or to avoid
      potential interference from maternally derived antibodies (MDA). Accordingly, a
      range of mucosal adjuvants (particularly those derived from bacteria) has been
      tested, and live recombinant vectored vaccines may also be effectively delivered
      by this route.

PMID- 17559865
TI  - Effective priming of foals born to immune dams against influenza by a canarypox
      vectored recombinant influenza H3N8 vaccine.
AB  - A classical limitation of early life immunization is the interference by
      maternally derived antibodies, which are known to inhibit the immune response to
      modified-live and killed vaccines. Several studies have convincingly shown that
      even minute amounts of maternally derived antibodies against equine influenza can
      strongly interfere with successful vaccination of foals born to immune mares. In
      this study we evaluated the response of foals born to vaccinated mares to
      immunization with a canarypox-vectored recombinant vaccine against equine
      influenza virus H3N8. The recombinant vaccine was able to efficiently prime foals
      in the presence of maternally derived immunity against influenza as was evidenced
      by a clear anamnestic antibody response when a secondary vaccination with the
      same vaccine was performed. The canarypox-vectored recombinant influenza vaccine
      therefore offers a unique opportunity to overcome the limitations of early life
      vaccination in the face of maternally derived immunity in foals.

PMID- 17559866
TI  - Protection of newborn animals through maternal immunization.
AB  - Providing protective immunity to neonatal animals in early life is associated
      with numerous challenges regarding vaccine safety and efficacy. A much simpler
      approach is maternal vaccination, either before or during pregnancy, to provide
      the neonate with passively transferred immunity. In humans, the medical, societal
      and legal risks of immunizing pregnant women are important considerations in
      undertaking this approach. By contrast, maternal vaccination has been
      successfully employed in the animal health industry for decades. These veterinary
      vaccines have proven to be safe and efficient. Although only passively
      transferred antibodies have been extensively studied, other immunological
      mechanisms may be equally important in providing maternally derived immunity.

PMID- 17559867
TI  - The challenges of vaccine responses in early life: selected examples.
AB  - One of the major challenges in vaccinology is the development of products that
      are able to induce protective immunity in the early life period. There are clear
      differences between adult and neonatal immune responses in both mice and humans
      with respect to both humoral and cell-mediated immunity. As a rule, neonates
      respond poorly to T-independent polysaccharide antigens and make lower and less
      persistent antibody responses to T-dependent protein antigens. Nevertheless, B
      cell priming in neonates may lead to the generation of memory B cells. Similarly,
      neonatal cell-mediated immune responses are of lower potency than those generated
      in adults, and a key factor underlying this phenomenon may be a less effective
      interaction between antigen and neonatal dendritic cells. In addition to
      immunological immaturity in the neonate, the presence of inhibitory
      concentrations of maternally derived antibody imposes a further barrier to
      effective early life vaccination. Novel vaccination strategies including early
      priming and subsequent boosting are most likely to counteract these effects and
      provide protection from exposure to infectious disease in early life.

PMID- 17559868
TI  - Proceedings of The Merial European Vaccinology Symposium, 2-4 November 2006,
      Athens, Greece.

PMID- 17559869
TI  - Mechanisms underlying adverse reactions to vaccines.
AB  - A broad spectrum of adverse events is reported following human vaccination but
      such reactions are considered to be relatively rare. A variety of mechanisms has
      been proposed to account for such adverse events. These most commonly relate to
      the actual process of vaccination and range from the vagal reaction associated
      with anxiety about needle injection, to use of an inappropriate site of
      administration, or infection of the healthcare worker by accidental injection
      during needle-capping. Other adverse events directly associated with the vaccine
      include reversion to virulence of attenuated vaccine strains of organisms, or
      contamination of the vaccine product. Adverse events may involve immune-mediated
      phenomena triggered by exposure to the microbial or other components of vaccines.
      These include: classical IgE-mediated type I hypersensitivity reactions, and
      immune-complex type III hypersensitivity (Arthus) reactions. Such reactions may
      be localized or systemic in nature. A variety of autoimmune reactions has been
      suggested to be triggered by vaccination, but in general the evidence for such
      associations remains largely anecdotal. Finally, many reported adverse events are
      simply chance instances of infection or disease onset around the time of
      vaccination and are not causally associated with administration of vaccine.

PMID- 17559870
TI  - Mixing memories: the effects of rumors that conflict with children's experiences.
AB  - This study examined age differences in children's vulnerability to be misled by
      two types of false overheard rumors, namely a rumor that suggested a reasonable
      explanation for an earlier unresolved experience and a rumor that suggested an
      explanation that conflicted with information already in memory. Results indicated
      that all of the children were highly susceptible to wrongly report the rumor as
      an actual experience when it merely filled a gap in memory. However, the 5- and 6
      year-olds were better able than the 3- and 4-year-olds to resist the rumor when
      it suggested a conflicting explanation for a past event. Developmental changes in
      children's understanding of conflicting mental representations were linked to
      their ability to resist being misled by the conflicting rumor.

PMID- 17559871
TI  - Comparison of the catalytic parameters and reaction specificities of a phage and
      an archaeal flap endonuclease.
AB  - Flap endonucleases (FENs) catalyse the exonucleolytic hydrolysis of blunt-ended
      duplex DNA substrates and the endonucleolytic cleavage of 5'-bifurcated nucleic
      acids at the junction formed between single and double-stranded DNA. The
      specificity and catalytic parameters of FENs derived from T5 bacteriophage and
      Archaeoglobus fulgidus were studied with a range of single oligonucleotide DNA
      substrates. These substrates contained one or more hairpin turns and mimic
      duplex, 5'-overhanging duplex, pseudo-Y, nicked DNA, and flap structures. The FEN
      catalysed reaction properties of nicked DNA and flap structures possessing an
      extrahelical 3'-nucleotide (nt) were also characterised. The phage enzyme
      produced multiple reaction products of differing length with all the substrates
      tested, except when the length of duplex DNA downstream of the reaction site was
      truncated. Only larger DNAs containing two duplex regions are effective
      substrates for the archaeal enzyme and undergo reaction at multiple sites when
      they lack a 3'-extrahelical nucleotide. However, a single product corresponding
      to reaction 1 nt into the double-stranded region occurred with A. fulgidus FEN
      when substrates possessed a 3'-extrahelical nt. Steady-state and pre-steady-state
      catalytic parameters reveal that the phage enzyme is rate-limited by product
      release with all the substrates tested. Single-turnover maximal rates of reaction
      are similar with most substrates. In contrast, turnover numbers for T5FEN
      decrease as the size of the DNA substrate is increased. Comparison of the
      catalytic parameters of the A. fulgidus FEN employing flap and double-flap
      substrates indicates that binding interactions with the 3'-extrahelical
      nucleotide stabilise the ground state FEN-DNA interaction, leading to stimulation
      of comparative reactions at DNA concentrations below saturation with the single
      flap substrate. Maximal multiple turnover rates of the archaeal enzyme with flap
      and double flap substrates are similar. A model is proposed to account for the
      varying specificities of the two enzymes with regard to cleavage patterns and
      substrate preferences.

PMID- 17559872
TI  - Dynamic allostery in the ring protein TRAP.
AB  - We have discovered distinct, characteristic differences in the thermodynamic
      signatures of tryptophan binding by trp RNA-binding attenuation protein (TRAP)
      from two different bacterial species. The TRAP 11mer ring binds 11 molecules of
      tryptophan at symmetry-related sites. Tryptophan binding to Bacillus
      stearothermophilus TRAP is not cooperative, but isothermal titration calorimetry
      shows that filling the first tryptophan binding sites of Bacillus subtilis TRAP
      has a marked effect on the thermodynamics of subsequent ligand binding. We have
      identified a single, conservative amino acid replacement (Ile to Leu) in B.
      subtilis TRAP that abolishes this effect, and suggest the initial ligand binding
      causes a change throughout the wild-type protein ring.

PMID- 17559873
TI  - Structure and mechanism of HpcG, a hydratase in the homoprotocatechuate
      degradation pathway of Escherichia coli.
AB  - HpcG catalyses the hydration of a carbon-carbon double bond without the aid of
      any cofactor other than a simple divalent metal ion such as Mg(2+). Since the
      substrate has a nearby carbonyl group, it is believed that it first isomerises to
      form a pair of conjugated double bonds in the enol tautomer before Michael
      addition of water. Previous chemical studies of the reaction, and that of the
      related enzyme MhpD, have failed to provide a clear picture of the mechanism. The
      substrate itself is unstable, preventing co-crystallisation or soaking of
      crystals, but oxalate is a strong competitive inhibitor. We have solved the
      crystal structure of the protein in the apo form, and with magnesium and oxalate
      bound. Modelling substrate into the active site suggests the attacking water
      molecule is not part of the metal coordination shell, in contrast to a previous
      proposal. Our model suggests that geometrically strained cis isomer intermediates
      do not lie on the reaction pathway, and that separate groups are involved in the
      isomerisation and hydration steps.

PMID- 17559874
TI  - The structure of serine palmitoyltransferase; gateway to sphingolipid
      biosynthesis.
AB  - Sphingolipid biosynthesis commences with the condensation of L-serine and
      palmitoyl-CoA to produce 3-ketodihydrosphingosine (KDS). This reaction is
      catalysed by the PLP-dependent enzyme serine palmitoyltransferase (SPT; EC
      2.3.1.50), which is a membrane-bound heterodimer (SPT1/SPT2) in eukaryotes such
      as humans and yeast and a cytoplasmic homodimer in the Gram-negative bacterium
      Sphingomonas paucimobilis. Unusually, the outer membrane of S. paucimobilis
      contains glycosphingolipid (GSL) instead of lipopolysaccharide (LPS), and SPT
      catalyses the first step of the GSL biosynthetic pathway in this organism. We
      report here the crystal structure of the holo-form of S. paucimobilis SPT at 1.3
      A resolution. The enzyme is a symmetrical homodimer with two active sites and a
      monomeric tertiary structure consisting of three domains. The PLP cofactor is
      bound covalently to a lysine residue (Lys265) as an internal aldimine/Schiff base
      and the active site is composed of residues from both subunits, located at the
      bottom of a deep cleft. Models of the human SPT1/SPT2 heterodimer were generated
      from the bacterial structure by bioinformatics analysis. Mutations in the human
      SPT1-encoding subunit have been shown to cause a neuropathological disease known
      as hereditary sensory and autonomic neuropathy type I (HSAN1). Our models provide
      an understanding of how these mutations may affect the activity of the enzyme.

PMID- 17559875
TI  - The crystal structure of the human Mov34 MPN domain reveals a metal-free dimer.
AB  - The 26S proteasome is a large protein complex involved in protein degradation. We
      have shown previously that the PSMD7/Mov34 subunit of the human proteasome
      contains a proteolytically resistant MPN domain. MPN domain family members
      comprise subunits of the proteasome, COP9-signalosome and translation initiation
      factor 3 complexes. Here, the crystal structure of two C-terminally truncated
      proteins, MPN 1-186 and MPN 1-177, were solved to 1.96 and 3.0 A resolution,
      respectively. MPN 1-186 is formed by nine beta-strands surrounded by three alpha
      helices plus a fourth alpha-helix at the C terminus. This final alpha-helix
      emerges from the domain core and folds along with a symmetrically related
      subunit, typical of a domain swap. The crystallographic dimer is consistent with
      size-exclusion chromatography and DLS analysis showing that MPN 1-186 is a dimer
      in solution. MPN 1-186 shows an overall architecture highly similar to the
      previously reported crystal structure of the Archaeal MPN domain AfJAMM of
      Archaeoglobus fulgidus. However, previous structural and biophysical analyses
      have shown that neither MPN 1-186 nor full-length human Mov34 bind metal, in
      opposition to the zinc-binding AfJAMM structures. The zinc ligand residues
      observed in AfJAMM are conserved in the yeast Rpn11 proteasome and Csn5 COP
      signalosome subunits, which is consistent with the isopeptidase activity
      described for these proteins. The results presented here show that, although the
      MPN domain of Mov34 shows a typical metalloprotease fold, it is unable to
      coordinate a metal ion. This finding and amino acid sequence comparisons can
      explain why the MPN-containing proteins Mov34/PSMD7, RPN8, Csn6, Prp8p and the
      translation initiation factor 3 subunits f and h do not show catalytic
      isopeptidase activity, allowing us to propose the hypothesis that in these
      proteins the MPN domain has a primarily structural function.

PMID- 17559876
TI  - Elastic behavior of RecA-DNA helical filaments.
AB  - Escherichia coli RecA protein forms a right-handed helical filament with DNA
      molecules and has an ATP-dependent activity that exchanges homologous strands
      between single-stranded DNA (ssDNA) and duplex DNA. We show that the RecA-ssDNA
      filamentous complex is an elastic helical molecule whose length is controlled by
      the binding and release of nucleotide cofactors. RecA-ssDNA filaments were
      fluorescently labelled and attached to a glass surface inside a flow chamber.
      When the chamber solution was replaced by a buffer solution without nucleotide
      cofactors, the RecA-ssDNA filament rapidly contracted approximately 0.68-fold
      with partial filament dissociation. The contracted filament elongated up to 1.25
      fold when a buffer solution containing ATPgammaS was injected, and elongated up
      to 1.17-fold when a buffer solution containing ATP or dATP was injected. This
      contraction-elongation behavior was able to be repeated by the successive
      injection of dATP and non-nucleotide buffers. We propose that this elastic motion
      couples to the elastic motion and/or the twisting rotation of DNA strands within
      the filament by adjusting their helical phases.

PMID- 17559877
TI  - Cerebral changes and cognitive dysfunctions in medication-free schizophrenia - an
      fMRI study.
AB  - Proposing cognitive impairment in working memory (wm) functions as a cognitive
      core deficit in schizophrenia, 23 first episode, medication-free schizophrenic
      patients in a comparison of healthy adults have been investigated by fMRI.
      Additionally, the effects of different attentional demands in wm tasks were
      analysed. A wm paradigm was applied, in which stimuli were presented in a 2-back
      and a 0-back condition in a non-degraded and degraded version. As hypothesized in
      healthy controls increased activity during both 2-back tasks was found in the
      ventrolateral prefrontal cortex (VLPFC), dorsolateral prefrontal cortex (DLPFC),
      parietal regions, the thalamus and the cerebellum. Different activation patterns
      were found for the cingulate cortex in the 2-back degraded conditions. The
      comparison between healthy controls and schizophrenic patients revealed decreased
      activity in the right VLPFC in patients as well as increased activity in temporal
      regions. Furthermore patients' task performance quality was significantly lower
      for 2-back conditions. Schizophrenic patients use different cognitive strategies
      to solve working memory tasks, reflected in significantly altered cerebral
      activity. However, the different fMRI working memory correlates found in
      schizophrenic patients seem to be insufficient in terms of overall task
      performance.

PMID- 17559878
TI  - Apoptotic death in deep partial thickness burns vs. normal skin of burned
      patients.
AB  - BACKGROUND: Deep partial thickness burns have an ambiguous behavior evolving
      either into spontaneous healing or full thickness burns. The aim of this study
      was to investigate these lesions for the presence of apoptosis thereby giving a
      possible cellular explanation to their peculiar clinical progression. METHODS: We
      used colocalization of DNA fragments (terminal deoxynucleotidyl transferase
      mediated dUTP nick end labeling) and Fas ligand CD95 antibodies to calculate the
      apoptotic rate of deep partial thickness burns and normal skin in 21 patients
      after acute thermal injuries (significant difference considered: P < 0.05).
      RESULTS: Deep partial thickness burns were associated with a higher apoptotic
      rate than normal skin (48.15% +/- 17.22% versus 18.6% +/- 7.2%; P = 0.0002).
      There were no apparent significant correlations of apoptotic rate with age, days
      from injury, total burn surface area or deep burn area except for a slight
      correlation with sex (r = 0.484; P = 0.02). CONCLUSIONS: A higher apoptotic rate
      was present in dermal cells of deep partial thickness burns if compared to that
      of the unburned skin. These data would suggest that deep partial thickness
      progression derive from apoptosis. Specific studies are required to confirm this
      hypothesis and to investigate its clinical and therapeutic significance.

PMID- 17559879
TI  - The mechanism of how anti-IL-18 prevents concanavalin-A-induced hepatic fibrosis
      on a mouse model.
AB  - BACKGROUND: The administration of concanavalin A (ConA) induces severe hepatic
      fibrosis in mice. Tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN
      gamma) and interleukin 4 (IL-4) were the key cytokines involved in the process.
      The aim of this research was to explore the effects and the mechanisms of IL-18
      and anti-IL-18 on hepatic fibrosis in a ConA induced hepatic fibrosis model in
      BABL-C mice. MATERIALS AND METHODS: One hundred eighty BABL-C mice were randomly
      divided into five groups (Group a, b, c, d, e). The mice were administered
      saline, immunoglobulin G, ConA, IL-18 + ConA, Anti-IL-18 + ConA, respectively. At
      1, 7, 14, 21 wk, the levels of serum alanine aminotransferase, TNF-alpha, IFN
      gamma, IL-4, matrix metalloproteinase (MMP)-2-RNA, and tissue inhibitor of
      metalloproteinase-1-mRNA were measured. RESULTS: The levels of serum TNF-alpha
      and IFN-gamma detected in the IL-18 + ConA group was higher than in the anti-IL
      18 + ConA group (P < 0.05). Similarly, the levels of MMP-2-RNA and tissue
      inhibitor of metalloproteinase-1-mRNA expressed in IL-18 + ConA group was higher
      than in the anti-IL-18 + ConA group (P < 0.05). A majority of these cytokines was
      secreted by CD4(+)T cells. CONCLUSIONS: The immunological response to hepatic
      fibrosis by repeated injection of ConA in the mouse model was aggravated by IL-18
      and blocked by anti-IL-18.

PMID- 17559880
TI  - Protective effects of combined ischemic preconditioning and ascorbic acid on
      mitochondrial injury in hepatic ischemia/reperfusion.
AB  - BACKGROUND: This study examined the in vivo effects of ischemic preconditioning
      (IPC), ascorbic acid (AA), or a combination (IPC + AA) on the level of
      mitochondrial injury caused by hepatic ischemia/reperfusion (I/R). MATERIALS AND
      METHODS: A rat liver was preconditioned with 10 min of ischemia followed by 10
      min of reperfusion, and then subjected to 90 min of ischemia followed by 5 h of
      reperfusion. The rats were pretreated with AA (100 mg/kg, i.v.) 5 min before the
      sustained ischemia. RESULTS: I/R increased the aminotransferase activity and
      level of mitochondrial lipid peroxidation, whereas it decreased the reduced
      glutathione:oxidized glutathione ratio. Either the IPC or AA pretreatment alone
      attenuated these changes, with the effect being enhanced by IPC + AA. The level
      of mitochondrial glutamate dehydrogenase, which is specifically located in the
      matrix, decreased after I/R but this was prevented by IPC + AA. Significant
      peroxide production was observed after 10 min of reperfusion after sustained
      ischemia. This change was attenuated by either IPC or AA alone and was further
      attenuated by IPC + AA. The mitochondria isolated after I/R were rapidly swollen,
      indicating an opening of the permeability transition pore. However, this was
      markedly reduced by IPC + AA. The hepatic ATP level was lower after I/R, which
      was restored by IPC alone and IPC + AA. CONCLUSIONS: Our findings suggest that
      IPC and AA synergistically reduce the level of mitochondrial damage during I/R as
      a result of decreased postischemic oxidant stress.

PMID- 17559881
TI  - Statins inhibit neutrophil infiltration in skeletal muscle reperfusion injury.
AB  - BACKGROUND: Neutrophil infiltration is a major determinant of ischemia
      reperfusion injury (IRI). Statins improve endothelial function by elevating
      nitric oxide synthase activity and inhibiting adhesion molecule expression and
      may, therefore, inhibit IRI-induced neutrophil extravasation. Although statins
      are protective against myocardial IRI and stroke, a role for statins in
      ameliorating skeletal muscle IRI has not yet been confirmed. This study,
      therefore, addressed the hypothesis that simvastatin would attenuate the severity
      of tissue damage during skeletal muscle IRI. METHODS: Rats were administered
      simvastatin for 6 d before 4 h hind limb ischemia and 24 h reperfusion.
      Neutrophil infiltration was assessed using myeloperoxidase (MPO) assays and
      tissue damage by quantitative immunohistochemical analysis of collagen IV. The
      effect of reducing nitric oxide levels on the severity of IRI was assessed by
      administering the NOS inhibitor, N-Imino-L-ornithine (L-NIO), before ischemia.
      RESULTS: Simvastatin significantly inhibited IRI-induced MPO activity but not
      collagen degradation in postischemic skeletal muscle. Inhibition of nitric oxide
      synthase by L-NIO markedly inhibited neutrophil infiltration and protected
      against IRI-induced collagen degradation. When both simvastatin and L-NIO were
      administered before IRI, the IRI-induced elevation in MPO activity was completely
      inhibited. However, paradoxically, simvastatin counteracted the protective effect
      of L-NIO against IRI-induced collagen IV degradation. CONCLUSIONS: The inhibition
      by simvastatin of IRI-induced neutrophil infiltration in skeletal muscle suggests
      that statins may be a useful therapy to attenuate the severity of IRI but their
      precise mechanisms of action remains to be determined. Nitric oxide also plays a
      cytotoxic, rather than protective, role in mediating IRI in this model.

PMID- 17559882
TI  - Androgen receptor blockade in experimental combination therapy of pancreatic
      cancer.
AB  - BACKGROUND: Reports on hormone receptor expression of pancreatic cancer (PaCa)
      cells and treatment responses to antihormonal therapy are still conflicting.
      METHODS: Eight human PaCa cell lines were tested for androgen receptor (AR)
      protein levels by Western blot analysis. Cell proliferation in vitro was measured
      by sulforhodamine B analysis. AR agonists and inhibitors included
      dihydrotestosterone (DHT), testosterone (T), and flutamide (Flu). In vivo therapy
      of nude mouse xenografts tested Flu with gemcitabine (Gem) and/or bevacizumab
      (Bev). RESULTS: Seven of eight human PaCa cell lines expressed detectable AR
      protein. Median relative expression compared with the AR positive control LnCaP
      was 21% (range: 16 to 63). Growth stimulation by DHT or T was minor (<20%);
      inhibition by Flu varied greatly and did not correlate to AR levels. Even in the
      sensitive cell line Panc1, Flu failed to increase Gem toxicity in vitro. However,
      in vivo Flu therapy resulted in significant growth inhibition of Panc-1 tumors.
      Flu/Gem treatment did not enhance the effect; Bev/Flu/Gem triple therapy had the
      greatest effect (P = 0.06 compared to Flu/Gem). Flu alone did not affect
      apoptotic activity, but decreased the tumor cell proliferative index (P = 0.04);
      in combination with Gem, Flu reduced the tumor cell density (P = 0.02).
      CONCLUSIONS: The majority of PaCa cell lines express AR at various levels, but
      most fail to show an in vitro antiproliferative response to AR inhibition. The
      strong antitumor effect of flutamide in vivo is not significantly enhanced in
      combination with gemcitabine or bevacizumab, suggesting primarily monotherapy
      benefit potential of AR blockade in susceptible PaCa.

PMID- 17559883
TI  - Hypothermia for neuroprotection after cardiac arrest: mechanisms, clinical trials
      and patient care.
AB  - Therapeutic hypothermia is a proven part of cardio-cerebral resuscitation after
      cardiac arrest as it improves neurologic outcomes after hypoxic brain injury.
      This article reviews the mechanisms of hypothermic neuroprotection, the clinical
      trials that support its use after cardiac arrest, as well as the impact of
      hypothermia on patient management and prognosis. In caring for patients suffering
      hypoxic brain injury after cardiac arrest, the role of the neurologist is no
      longer limited to prognosis but is now to become actively involved in clinical
      management which includes the use of therapeutic hypothermia.

PMID- 17559885
TI  - Modeling the primary auditory cortex using dynamic synapses: can synaptic
      plasticity explain the temporal tuning?
AB  - The molecular mechanisms underlying the temporal plasticity (temporal tuning) of
      cortical cells remain controversial. Experimental observations indicate that the
      neuronal responses at the primary auditory cortex are affected by behavioral
      learning. In this paper, we present a minimal feed-forward model of the primary
      auditory cortex, based on the dynamic synapse and the leaky integrate-and-fire
      neuron models, in order to search for the origin of the observed plasticity. We
      demonstrate that the frequency response of the model is markedly modified by
      regulating the contribution of synaptic facilitation to the short-term dynamics
      of synapses (U(1)). Consequently, we propose that the variation of this parameter
      may be responsible for primary auditory cortex enhancement achieved by behavioral
      training. Based on our model, we assume that the contribution of facilitation
      arises from the amount of Ca(2+) influx each time an action potential arrives at
      the nerve terminal. Regardless of what really leads to the long-term variation of
      Ca(2+) influx, we suggest that this process is responsible for the temporal
      tuning of responses observed in experimental studies. We believe that measurement
      of the long-term variation of Ca(2+) influx at the pre-synaptic area of the
      cortical cells in auditory learning trials would be the first step to validate
      our hypothesis.

PMID- 17559884
TI  - A mathematical model of fluid secretion from a parotid acinar cell.
AB  - Salivary fluid secretion is crucial for preventing problems such as dryness of
      mouth, difficulty with mastication and swallowing, as well as oral pain and
      dental cavities. Fluid flow is driven primarily by the transepithelial movement
      of chloride and sodium ions into the parotid acinus lumen. The activation of Cl(
      ) channels is calcium dependent, with the average elevated calcium concentration
      during calcium oscillations increasing the conductance of the channels, leading
      to an outflow of Cl(-). The accumulation of NaCl in the lumen drives water flow
      by osmosis. We construct a mathematical model of the calcium concentration
      oscillations and couple this to a model for Cl(-) efflux. We also construct a
      model governing fluid flow in an isolated parotid acinar cell, which includes a
      description of the rate of change of intracellular ion concentrations, cell
      volume, membrane potential and water flow rate. We find that [Ca(2+)]
      oscillations lead to oscillations in fluid flow, and that the rate of fluid flow
      is regulated by the average calcium concentration and not the frequency of the
      oscillations.

PMID- 17559886
TI  - Signaling perturbations induced by invading H. pylori proteins in the host
      epithelial cells: a mathematical modeling approach.
AB  - Helicobacter pylori (H. pylori), a gram-negative bacterium, infects the stomach
      of approximately 50% of the world population. H. pylori infection is a risk
      factor for developing chronic gastric ulcers and gastric cancer. The bacteria
      produce two main cytotoxic proteins: Vacuolating cytotoxin A (VacA) and Cytotoxin
      Associated gene A (CagA). When these proteins enter the host cell they interfere
      with the host MAP Kinase and Apoptosis signaling pathways leading to aberrant
      cell growth and premature apoptosis. The present study expanded existing
      quantitative models of the MAP Kinase and Apoptosis signaling pathways to take
      into account the protein interactions across species using the CellDesigner tool.
      The resulting network contained hundreds of differential equations in which the
      coefficients for the biochemical rate constants were estimated from previously
      published studies. The effect of VacA and CagA on the function of this network
      were simulated by increasing levels of bacterial load. Simulations showed that
      increasing bacterial load affected the MAP Kinase signaling in a dose dependant
      manner. The introduction of CagA decreased the activation time of mapK signaling
      and extended activation indefinitely despite normal cellular activity to
      deactivate the protein. Introduction of VacA produced a similar response in the
      apoptosis pathway. Bacterial load activated both pathways even in the absence of
      external stimulation. Time course of emergence of transcription factors
      associated with cell division and cell death predicted by our simulation showed
      close agreement with that determined from a publicly accessible microarray data
      set of H. pylori infected stomach epithelium. The quantitative model presented in
      this study lays the foundation for investigating the affects of single nucleotide
      polymorphisms (SNPs) on the efficiency of drug treatment.

PMID- 17559887
TI  - A mathematical model of the Drosophila circadian clock with emphasis on
      posttranslational mechanisms.
AB  - Experimental evidence points increasingly to the importance of posttranslational
      processes such as phosphorylation and translocation in the molecular circadian
      clocks of many organisms. We develop a mathematical model of the Drosophila
      circadian clock that incorporates the emerging details of the timing of nuclear
      translocation of the PERIOD and TIMELESS proteins. Most models assume that these
      proteins enter the nucleus as a complex, but recent experiments suggest that they
      in fact enter the nucleus separately. Our model reproduces observed patterns of
      intracellular localization of PERIOD and TIMELESS during light-dark cycles and in
      constant darkness, as well as phenotypes of several clock mutants. We also use
      the model to demonstrate how the Drosophila clock can exhibit robust oscillations
      with constant mRNA levels of period or timeless, and propose a possible mechanism
      for oscillations in double-rescue experiments of per(01)-tim(01) mutants. The
      model also explains (via posttranslational processes) the counter-intuitive
      observation that total dCLOCK levels are at their lowest at the circadian time
      when active nuclear dCLOCK must be peaking in order to activate transcription of
      other clock genes, implying that for dCLOCK a posttranslationally generated
      rhythm is more important than the transcriptionally generated rhythm. These
      results support the idea that posttranslational processes play key roles in
      generating as well as modulating robust circadian oscillations. While it appears
      that posttranslational mechanisms alone are not sufficient to generate rhythms in
      Drosophila, posttranslational mechanisms can greatly amplify a very weak
      transcriptional rhythm.

PMID- 17559888
TI  - Thrombospondin-based antiangiogenic therapy.
AB  - Thrombospondins (TSPs) are a family of extracellular matrix proteins that
      regulate tissue genesis and remodeling. TSP-1 plays a pivotal role in the
      regulation of both physiological and pathological angiogenesis. The inhibitory
      effects of TSP-1 on angiogenesis have been established in numerous experimental
      models. Among other TSP members, TSP-2 has equivalent domain structure as TSP-1
      and shares most functions of TSP-1. The mechanisms by which TSP-1 and -2 inhibit
      angiogenesis can be broadly characterized as direct effects on vascular
      endothelial cells and indirect effects on the various angiogenic regulators. The
      fact that TSP-1 and -2 are potent endogenous angiogenic inhibitors has prompted
      studies to explore their therapeutic applications, and detailed understanding of
      the mechanisms of action of TSP-1 and -2 has facilitated the design of
      therapeutic strategies to optimize these activities. The therapeutic effects can
      be achieved by up-regulation of endogenous TSPs, or by the delivery of
      recombinant proteins or synthetic peptides that contain sequences from the
      angiogenic domain of TSP-1. In this article, we review the progress in
      thrombospondin-based antiangiogenic therapy and discuss the perspectives on the
      significant challenges that remain.

PMID- 17559890
TI  - [Derivation of cerebrospinal fluid: consequences on inner ear biomechanics in
      adult patients with chronic hydrocephalus].
AB  - BACKGROUND AND PURPOSE: Patients suffering from hydrocephalus are often treated
      by the surgical placement of a shunt, directing the excess of cerebrospinal fluid
      towards another body compartment. However, the degree of clinical improvement is
      variable and the dynamics of cerebrospinal fluid pressure in shunted
      hydrocephalus is poorly understood. A recently developed noninvasive technique
      makes it possible to follow pressure variations: it is based on otoacoustic
      emissions, sounds naturally emitted by the cochlea and routinely detected in
      audiology. When cerebrospinal fluid pressure changes, emissions undergo a phase
      shift while crossing the oval window. The goal of this work is to study how this
      shift is affected by shunt placement. METHOD: Otoacoustic emissions were recorded
      repeatedly in 22 adult patients who suffered from chronic hydrocephalus. Their
      phase shifts were measured, in sitting and recumbent positions, before and after
      surgical placement of a ventriculo-peritoneal shunt (Sophysa SM8). RESULTS:
      Postural shift in normal subjects is a phase lead, and this outcome was found in
      17 of 22 patients preoperatively. After shunt placement, the postural effect
      became a phase lag in 18 patients of 20. In a given posture, sitting or
      recumbent, phase shifts changed from pre to postoperative measurements in a
      systematic manner. CONCLUSION: Otoacoustic emissions respond in a characteristic
      way to posture changes in normal adults, and having received a shunt for chronic
      hydrocephalus reverses the effect, presumably in relation to the existence of a
      "vacuum" in the inner ear.

PMID- 17559889
TI  - Complexity of type 2 diabetes mellitus data sets emerging from nutrigenomic
      research: a case for dimensionality reduction?
AB  - Nutrigenomics promises personalized nutrition and an improvement in preventing,
      delaying, and reducing the symptoms of chronic diseases such as diabetes.
      Nutritional genomics is the study of how foods affect the expression of genetic
      information in an individual and how an individual's genetic makeup affects the
      metabolism and response to nutrients and other bioactive components in food. The
      path to those promises has significant challenges, from experimental designs that
      include analysis of genetic heterogeneity to the complexities of food and
      environmental factors. One of the more significant complications in developing
      the knowledge base and potential applications is how to analyze high-dimensional
      datasets of genetic, nutrient, metabolomic (clinical), and other variables
      influencing health and disease processes. Type 2 diabetes mellitus (T2DM) is used
      as an illustration of the challenges in studying complex phenotypes with
      nutrigenomics concepts and approaches.

PMID- 17559891
TI  - Behavioral and neurochemical characterization of mice deficient in the
      phosphodiesterase-1B (PDE1B) enzyme.
AB  - PDE1B is a calcium-dependent cyclic nucleotide phosphodiesterase that is highly
      expressed in the striatum. In order to investigate the physiological role of
      PDE1B in the central nervous system, PDE1B knockout mice (C57BL/6N background)
      were assessed in behavioral tests and their brains were assayed for monoamine
      content. In a variety of well-characterized behavioral tasks, including the
      elevated plus maze (anxiety-like behavior), forced swim test (depression-like
      behavior), hot plate (nociception) and two cognition models (passive avoidance
      and acquisition of conditioned avoidance responding), PDE1B knockout mice
      performed similarly to wild-type mice. PDE1B knockout mice showed increased
      baseline exploratory activity when compared to wild-type mice. When challenged
      with amphetamine (AMPH) and methamphetamine (METH), male and female PDE1B
      knockout mice showed an exaggerated locomotor response. Male PDE1B knockout mice
      also showed increased locomotor responses to higher doses of phencyclidine (PCP)
      and MK-801; however, this effect was not consistently observed in female knockout
      mice. In the striatum, increased dopamine turnover (DOPAC/DA and HVA/DA ratios)
      was found in both male and female PDE1B knockout mice. Striatal serotonin (5-HT)
      levels were also decreased in PDE1B knockout mice, although levels of the
      metabolite, 5HIAA, were unchanged. The present studies demonstrate increased
      striatal dopamine turnover in PDE1B knockout mice associated with increased
      baseline motor activity and an exaggerated locomotor response to dopaminergic
      stimulants such as methamphetamine and amphetamine. These data further support a
      role for PDE1B in striatal function.

PMID- 17559892
TI  - Plant cell walls are enfeebled when attempting to preserve native lignin
      configuration with poly-p-hydroxycinnamaldehydes: evolutionary implications.
AB  - The lignin deficient double mutant of cinnamyl alcohol dehydrogenase (CAD, cad-4,
      cad-5 or cad-c, cad-d) in Arabidopsis thaliana [Sibout, R., Eudes, A., Mouille,
      G., Pollet, B., Lapierre, C., Jouanin, L., Seguin, A., 2005. Cinnamyl alcohol
      dehydrogenase-C and -D are the primary genes involved in lignin biosynthesis in
      the floral stem of Arabidopsis. Plant Cell 17, 2059-2076], was comprehensively
      examined for effects on disruption of native lignin macromolecular configuration;
      the two genes encode the catalytically most active CAD's for monolignol/lignin
      formation [Kim, S.-J., Kim, M.-R., Bedgar, D.L., Moinuddin, S.G.A., Cardenas,
      C.L., Davin, L.B., Kang, C., Lewis, N.G., 2004. Functional reclassification of
      the putative cinnamyl alcohol dehydrogenase multigene family in Arabidopsis.
      Proc. Natl. Acad. Sci., USA 101, 1455-1460]. The inflorescence stems of the
      double mutant presented a prostrate phenotype with dynamic modulus properties
      greatly reduced relative to that of the wild type (WT) line due to severe
      reductions in macromolecular lignin content. Interestingly, initially the overall
      pattern of phenolic deposition in the mutant was apparently very similar to WT,
      indicative of comparable assembly processes attempting to be duplicated. However,
      shortly into the stage involving (monomer cleavable) 8-O-4' linkage formation,
      deposition was aborted. At this final stage, the double mutant had retained a
      very limited ability to biosynthesize monolignols as evidenced by cleavage and
      release of ca. 4% of the monolignol-derived moieties relative to the lignin of
      the WT line. In addition, while small amounts of cleavable p
      hydroxycinnamaldehyde-derived moieties were released, the overall frequency of
      (monomer cleavable) 8-O-4' inter-unit linkages closely approximated that of WT
      for the equivalent level of lignin deposition, in spite of the differences in
      monomer composition. Additionally, 8-5' linked inter-unit structures were clearly
      evident, albeit as fully aromatized phenylcoumaran-like substructures. The data
      are interpreted as a small amount of p-hydroxycinnamaldehydes being utilized in
      highly restricted attempts to preserve native lignin configuration, i.e. through
      very limited monomer degeneracy during template polymerization which would
      otherwise afford lignins proper in the cell wall from their precursor
      monolignols. The defects introduced (e.g. in the vascular integrity) provide
      important insight as to why p-hydroxycinnamaldehydes never evolved as lignin
      precursors in the 350,000 or so extant vascular plant species. It is yet unknown
      at present, however, as to what levels of lignin reduction can be attained in
      order to maintain the requisite properties for successful agronomic/forestry
      cultivation. Nor is it known to what extent, if any, such deleterious modulations
      potentially compromise plant defenses. Finally, prior to investigating lignin
      primary structure proper, it is essential to initially define the fundamental
      characteristics of the biopolymer(s) being formed, such as inter-unit frequency
      and lignin content, in order to design approaches to determine overall sequences
      of linkages.

PMID- 17559893
TI  - From lignins to tannins: forty years of enzyme studies on the biosynthesis of
      phenolic compounds.
AB  - In the early 1960s, enzyme studies increasingly began to replace the common
      'feeding' experiments in which labeled tracers were applied to living plants or
      plant parts for elucidating metabolic pathways. This advanced technique allowed
      to gain much deeper insights into individual details of metabolic sequences, and
      particularly on the previously inaccessible role of activated 'energy-rich'
      intermediates. Based on the author's own experience for the past 40+ years in
      this field, principal findings and trends elucidating the pathways to lignin and
      lignin precursors, acyl amides and hydrolyzable tannins (gallotannins,
      ellagitannins) by enzyme studies are reported.

PMID- 17559894
TI  - Substrate cycles in the central metabolism of maize root tips under hypoxia.
AB  - Substrate cycles, also called "futile" cycles, are ubiquitous and lead to a net
      consumption of ATP which, in the normoxic maize root, have been estimated at
      about 50% of the total ATP produced [Alonso, A.P., Vigeolas, H., Raymond, P.,
      Rolin, D., Dieuaide-Noubhani, M., 2005. A new substrate cycle in plants. Evidence
      for a high glucose-phosphate-to-glucose turnover from in vivo steady-state and
      pulse-labeling experiments with [(13)C] glucose and [(14)C] glucose. Plant
      Physiol. 138, 2220-2232]. To evaluate their role we studied the substrate cycles
      of maize root tips under an oxygen limitation of respiration (3% O(2)). Short
      time labeling experiments with [U-(14)C]-Glc were performed to quantify the
      fluxes through sucrose and starch cycles of synthesis and degradation. Steady
      state labeling with [1-(13)C]-Glc followed by (1)H NMR and (13)C NMR analysis of
      sugars and free alanine was used to quantify fluxes in the central metabolic
      pathways, including the Glc-P/Glc cycle and the fructose-P/triose-P cycle of
      glycolysis. Comparison with results previously obtained in normoxia [Alonso et
      al., as mentioned above] showed that 3% O(2) induced fermentation and reduced
      respiration, which led to a lesser amount of ATP produced. The rates of Glc
      consumption, glycolytic flux and all substrate cycles were lower, but the
      proportion of ATP consumed in the substrate cycles remained unchanged. These
      findings suggest that substrate cycles are not a luxury but an integral part of
      the organization of the plant central metabolism.

PMID- 17559895
TI  - A proposed transpositional acupoint system in a mouse and rat model.
AB  - In acupuncture, the specificity of the point and the reproducibility of the
      location of the point are prerequisite to the specificity and reproducibility of
      research involving acupuncture stimulation. The transpositional method, which
      locates animal acupoints (AAs) on the surface of animal skin corresponding to the
      anatomic site of a human acupoint, has been generally adopted for research
      modeling. However, there remains a lack of consensus on the specific location of
      AA among researchers. The potential problems that the discrepancy in acupoint
      locating methods causes include the attempt to compare research results. This
      report is a conceptual study that calls attention to the problems of
      inconsistency in AA location, and proposes a transpositional 121 AA system in a
      mouse and rat model. Further discussion, and the establishment of reproducible
      transpositional AA systems, will prompt further quantitative research and
      exchange of scientific ideas.

PMID- 17559896
TI  - Moxidectin interference on sexual behavior, penile erection and hypothalamic GABA
      levels of male rats.
AB  - The moxidectin (MXD) is an antiparasitic drug used in domestic animals. The
      mechanism of action, in mammals, involves GABA, a neurotransmitter with an
      important role in the sexual behavior control. Presently, the effects of 0.2
      mg/kg therapeutic dose were studied on sexual behavior, sexual motivation, penile
      erection and central GABA levels. Sexual behavior results showed increased
      latencies to the first mount and intromission as well as in inter-intromission
      interval; a reduction in total mounts was detected on the drug post-treatment. No
      difference was observed between sexual motivation of control and experimental
      animals. MXD treatment reduced penile erection and hypothalamic GABA levels. The
      results suggest that MXD reduced sexual behavior and penile erection by an action
      on the hypothalamic GABA system. Probably, the lack of effects in the
      motivational test and the increased mount and intromission latencies as well as
      decreased total mounts could be explained as a consequence of reduced male rat
      erection process.

PMID- 17559897
TI  - Toxicity and cardiac effects of carbaryl in early developing zebrafish (Danio
      rerio) embryos.
AB  - Carbaryl, an acetylcholinesterase inhibitor, is known to be moderately toxic to
      adult zebrafish and has been reported to cause heart malformations and irregular
      heartbeat in medaka. We performed experiments to study the toxicity of carbaryl,
      specifically its effects on the heart, in early developing zebrafish embryos.
      LC50 and EC50 values for carbaryl at 28 h post-fertilization were 44.66 microg/ml
      and 7.52 microg/ml, respectively, and 10 microg/ml carbaryl was used in
      subsequent experiments. After confirming acetylcholinesterase inhibition by
      carbaryl using an enzymatic method, we observed red blood cell accumulation,
      delayed hatching and pericardial edema, but not heart malformation as described
      in some previous reports. Our chronic exposure data also demonstrated carbaryl
      induced bradycardia, which is a common effect of acetylcholinesterase inhibitors
      due to the accumulation of acetylcholine, in embryos from 1 day post
      fertilization (dpf) to 5 dpf. The distance between the sinus venosus, the point
      where blood enters the atrium, and the bulbus arteriosus, the point where blood
      leaves the ventricle, indicated normal looping of the heart tube. Immunostaining
      of myosin heavy chains with the ventricle-specific antibody MF20 and the atrium
      specific antibody S46 showed normal development of heart chambers. At the same
      time, acute exposure resulted in carbaryl-induced bradycardia. Heart rate dropped
      significantly after a 10-min exposure to 100 microg/ml carbaryl but recovered
      when carbaryl was removed. The novel observation of carbaryl-induced bradycardia
      in 1- and 2-dpf embryos suggested that carbaryl affected cardiac function
      possibly through an alternative mechanism other than acetylcholinesterase
      inhibition such as inhibition of calcium ion channels, since acetylcholine
      receptors in zebrafish are not functional until 3 dpf. However, the exact nature
      of this mechanism is currently unknown, and thus further studies are required.

PMID- 17559898
TI  - Cytotoxicity of diacetoxyscirpenol is associated with apoptosis by activation of
      caspase-8 and interruption of cell cycle progression by down-regulation of cdk4
      and cyclin B1 in human Jurkat T cells.
AB  - To understand the mechanism underlying T-cell toxicity of diacetoxyscirpenol
      (DAS) from Fusarium sambucinum, its apoptogenic as well as growth retardation
      activity was investigated in human Jurkat T cells. Exposure to DAS (0.01-0.15
      microM) caused apoptotic DNA fragmentation along with caspase-8 activation, Bid
      cleavage, mitochondrial cytochrome c release, activation of caspase-9 and caspase
      3, and PARP degradation, without any alteration in the levels of Fas or FasL.
      Under these conditions, necrosis was not accompanied. The cytotoxicity of DAS was
      not blocked by the anti-Fas neutralizing antibody ZB-4. Although the DAS-induced
      apoptotic events were completely prevented by overexpression of Bcl-xL, the cells
      overexpressing Bcl-xL were unable to divide in the presence of DAS, resulting
      from the failure of cell cycle progression possibly due to down-regulation in the
      protein levels of cdk4 and cyclin B1. The DAS-mediated apoptosis and activation
      of caspase-8, -9, and -3 were abrogated by either pan-caspase inhibitor (z-VAD
      fmk) or caspase-8 inhibitor (z-IETD-fmk). While the DAS-mediated apoptosis and
      activation of caspase-9 and caspase-3 were slightly suppressed by the
      mitochondrial permeability transition pore inhibitor (CsA), both caspase-8
      activation and Bid cleavage were not affected by CsA. The activated normal
      peripheral T cells possessed a similar susceptibility to the cytotoxicity of DAS.
      These results demonstrate that the T-cell toxicity of DAS is attributable to not
      only apoptosis initiated by caspase-8 activation and subsequent mitochondrion
      dependent or -independent activation of caspase cascades, which can be regulated
      by Bcl-xL, but also interruption of cell cycle progression caused by down
      regulation of cdk4 and cyclin B1 proteins.

PMID- 17559899
TI  - Tissue distribution and urinary excretion of dimethylated arsenic and its
      metabolites in dimethylarsinic acid- or arsenate-treated rats.
AB  - Adult female Fisher 344 rats received drinking water containing 0, 4, 40, 100, or
      200 parts per million of dimethylarsinic acid or 100 parts per million of
      arsenate for 14 days. Urine was collected during the last 24 h of exposure.
      Tissues were then taken for analysis of dimethylated and trimethylated
      arsenicals; urines were analyzed for these arsenicals and their thiolated
      derivatives. In dimethylarsinic acid-treated rats, highest concentrations of
      dimethylated arsenic were found in blood. In lung, liver, and kidney,
      concentrations of dimethylated arsenic exceeded those of trimethylated species;
      in urinary bladder and urine, trimethylated arsenic predominated.
      Dimethylthioarsinic acid and trimethylarsine sulfide were present in urine of
      dimethylarsinic acid-treated rats. Concentrations of dimethylated arsenicals were
      similar in most tissues of dimethylarsinic acid- and arsenate-treated rats,
      including urinary bladder which is the target for dimethylarsinic acid-induced
      carcinogenesis in the rat. Mean concentration of dimethylated arsenic was
      significantly higher (P<0.05) in urine of dimethylarsinic acid-treated rats than
      in arsenate-treated rats, suggesting a difference between treatment groups in the
      flux of dimethylated arsenic through urinary bladder. Concentrations of
      trimethylated arsenic concentrations were consistently higher in dimethylarsinic
      acid-treated rats than in arsenate-treated rats; these differences were
      significant (P<0.05) in liver, urinary bladder, and urine. Concentrations of
      dimethylthioarsinic acid and trimethylarsine sulfide were higher in urine from
      dimethylarsinic acid-treated rats than from arsenate-treated rats.
      Dimethylarsinic acid is extensively metabolized in the rat, yielding significant
      concentrations of trimethylated species and of thiolated derivatives. One or more
      of these metabolites could be the species causing alterations of cellular
      function that lead to tumors in the urinary bladder.

PMID- 17559900
TI  - Characterization of peptide components in the venom of the scorpion Liocheles
      australasiae (Hemiscorpiidae).
AB  - Scorpion venoms are composed of a number of neurotoxic peptides. A variety of
      toxins have been isolated from the venoms of scorpions of the family Buthidae,
      however, little interest has been paid to non-Buthidae scorpions. In this study,
      we examined the toxicity of the venom of Liocheles australasiae (Hemiscorpiidae)
      to mice and crickets, and characterized the peptide components by HPLC and mass
      spectrometry. Over 200 components were detected in the L. australasiae venom by
      LC/MS analysis, with components of molecular masses ranging from 500 to 5000 Da
      being particularly abundant. A number of peptides contained two to four disulfide
      bridges, which was estimated based on the mass difference after derivatization of
      Cys residues. A peptide having a monoisotopic molecular mass of 7781.6 Da and
      four disulfide bridges was isolated from the venom. The peptide has a primary
      structure similar in terms of the position of eight Cys residues to those
      observed in several peptides found from scorpions, ticks and insects, although
      biological roles of these peptides are unknown.

PMID- 17559901
TI  - Characterization of small RNAs derived from Citrus exocortis viroid (CEVd) in
      infected tomato plants.
AB  - In plants, RNA silencing provides an adaptive immune system that inactivates
      pathogenic nucleic acids, guided by 21-24-mer RNAs of pathogen origin. The
      characterization of pathogen-related small RNAs (sRNAs) is relevant to uncovering
      the strategies used by pathogens to evade host defense responses. Several groups
      have reported the detection of viroid-derived sRNAs during infections, although
      the origin of these sRNAs and their chemical characteristics were poorly
      understood. Here, we describe the in vivo cleavage of Citrus exocortis viroid
      (CEVd) RNA into sRNAs of 21-22 nt, that are phosphorylated at their 5'-end and
      methylated at 3'. Our studies suggested that the CEVd genomic RNA might be the
      predominant in vivo substrate for cleavage by Dicer-like enzyme(s), which
      preferentially targeted residues mainly located within the right-end domain of
      the viroid. Further analysis on the accumulation levels of specific miRNAs
      controlling major regulators of leaf development and the miRNA pathway and the
      levels of their target mRNAs provided evidence that the endogenous tomato miRNA
      pathway was not affected by CEVd infection.

PMID- 17559902
TI  - Interferons induce an antiviral state in human pancreatic islet cells.
AB  - Enterovirus infections, in particular those with Coxsackieviruses, have been
      linked to the development of type 1 diabetes (T1D). Although animal models have
      demonstrated that interferons (IFNs) regulate virus-induced T1D by acting
      directly on the beta cell, little is known on the human pancreatic islet response
      to IFNs. Here we show that human islet cells respond to IFNs by expressing
      signature genes of antiviral defense. We also demonstrate that they express three
      intracellular sensors for viral RNA, the toll like receptor 3 (TLR3) gene, the
      retinoic acid-inducible gene I (RIG-I) and the melanoma differentiation
      associated gene-5 (MDA-5), which induce type I IFN production in infected cells.
      Finally, we show for the first time that the IFN-induced antiviral state provides
      human islets with a powerful protection from the replication of Coxsackievirus.
      This may be critical for beta cell survival and protection from virus-induced T1D
      in humans.

PMID- 17559903
TI  - Importance of the short cytoplasmic domain of the feline immunodeficiency virus
      transmembrane glycoprotein for fusion activity and envelope glycoprotein
      incorporation into virions.
AB  - The mature form of the envelope (Env) glycoprotein of lentiviruses is a
      heterodimer composed of the surface (SU) and transmembrane (TM) subunits. Feline
      immunodeficiency virus (FIV) possesses a TM glycoprotein with a cytoplasmic tail
      of approximately 53 amino acids which is unusually short compared with that of
      the other lentiviral glycoproteins (more than 100 residues). To investigate the
      relevance of the FIV TM cytoplasmic domain to Env-mediated viral functions, we
      characterized the biological properties of a series of Env glycoproteins
      progressively shortened from the carboxyl terminus. All the mutant Env proteins
      were efficiently expressed in feline cells and processed into the SU and TM
      subunits. Deletion of 5 or 11 amino acids from the TM C-terminus did not
      significantly affect Env surface expression, fusogenic activity or Env
      incorporation into virions, whereas removal of 17 or 23 residues impaired Env
      mediated cell-to-cell fusion. Further truncation of the FIV TM by 29 residues
      resulted in an Env glycoprotein that was poorly expressed at the cell surface,
      exhibited only 20% of the wild-type Env fusogenic capacity and was inefficiently
      incorporated into virions. Remarkably, deletion of the TM C-terminal 35 or 41
      amino acids restored or even enhanced Env biological functions. Indeed, these
      mutant Env glycoproteins bearing cytoplasmic domains of 18 or 12 amino acids were
      found to be significantly more fusogenic than the wild-type Env and were
      efficiently incorporated into virions. Interestingly, truncation of the TM
      cytoplasmic domain to only 6 amino acids did not affect Env incorporation into
      virions but abrogated Env fusogenicity. Finally, removal of the entire TM
      cytoplasmic tail or deletion of as many as 6 amino acids into the membrane
      spanning domain led to a complete loss of Env functions. Our results demonstrate
      that despite its relatively short length, the FIV TM cytoplasmic domain plays an
      important role in modulating Env-mediated viral functions.

PMID- 17559904
TI  - The continuous Wagon Wheel Illusion depends on, but is not identical to neuronal
      adaptation.
AB  - The occurrence of perceived reversed motion while observers view a continuous,
      periodically moving stimulus (a bistable phenomenon coined the "continuous Wagon
      Wheel Illusion" or "c-WWI") has been taken as evidence that some aspects of
      motion perception rely on discrete sampling of visual information. Alternative
      accounts rely on the possibility of a motion aftereffect that may become visible
      even while the adapting stimulus is present. Here I show that motion adaptation
      might be necessary, but is not sufficient to explain the illusion. When local
      adaptation is prevented by slowly drifting the moving wheel across the retina,
      the c-WWI illusion tends to decrease, as do other bistable percepts (e.g.
      binocular rivalry). However, the strength of the c-WWI and that of adaptation (as
      measured by either the static or flicker motion aftereffects) are not directly
      related: although the c-WWI decreases with increasing eccentricity, the
      aftereffects actually intensify concurrently. A similar dissociation can be
      induced by manipulating stimulus contrast. This indicates that the c-WWI may be
      enabled by, but is not equivalent to, local motion adaptation - and that other
      factors such as discrete sampling may be involved in its generation.

PMID- 17559905
TI  - Differences in discrimination of eye and mouth displacement in autism spectrum
      disorders.
AB  - Individuals with Autism Spectrum Disorders (ASD) have been found to have
      impairments in some face recognition tasks [e.g., Boucher, J., & Lewis, V.
      (1992). Unfamiliar face recognition in relatively able autistic children. Journal
      of Child Psychology and Psychiatry, 33, 843-859.], and it has been suggested that
      this impairment occurs because these individuals do not spontaneously attend to
      the eyes [e.g., Pelphrey, K. A., Sasson, N. J., Reznick, J. S., Paul, G.,
      Goldman, B. D., & Piven, J. (2002). Visual scanning of faces in autism. Journal
      of Autism and Developmental Disorders, 32, 249-261.], or attend selectively to
      the mouth [e.g., Langdell, T. (1978). Recognition of faces-approach to study of
      autism. Journal of Child Psychology and Psychiatry and Allied Disciplines, 19,
      255-268; Joseph, R. M., & Tanaka J. (2003). Holistic and part-based face
      recognition in children with autism. Journal of Child Psychology and Psychiatry,
      44, 529-542.]. Here, we test whether the eyes or the mouth are attended to
      preferentially by 16 males with ASD and 19 matched controls. Participants
      discriminated small spatial displacements of the eyes and the mouth. If the mouth
      region were attended to preferentially by individuals with ASD, we would expect
      ASD observers to be better at detecting subtle changes in mouth than eye
      displacements, relative to controls. Further, following Barton [Barton, J. J. S.,
      Keenan, J. P., & Bass, T. (2001). Discrimination of spatial relations and
      features in faces: Effects of inversion and viewing duration. British Journal of
      Psychology, 92, 527-549.], we would expect to see differences in inversion
      effects as a function of feature manipulation between ASD and control groups. We
      found that individuals with ASD performed significantly differently than controls
      for the eye, but not the mouth, trials. However, we found no difference in
      inversion effects between the two groups of observers. Furthermore, we found
      evidence of distinct subclasses of individuals with ASD: those who performed
      normally, and those who were impaired. These results suggests that typical
      individuals are better able to make use of information in the eyes than some
      individuals with ASD, but that there is no clear autism "advantage" in the use of
      information in the mouth region.

PMID- 17559906
TI  - Modeling binding equilibrium in a competitive estrogen receptor binding assay.
AB  - Although the free concentration is more significant in the environmental
      chemistry and toxicology of receptor-mediated toxicants, few studies have been
      conducted to use it as a dose-metric. The relative binding affinity of three
      model endocrine disrupting compounds, diethylstilbestrol (DES), ethynylestradiol
      (EE2), and bisphenol A (BPA), were evaluated using a competitive ELISA with human
      estrogen receptor alpha. After measuring the available receptors and the
      dissociation constant for 17beta-estradiol, binding inhibition curves using the
      free concentration as the dose-metric were obtained by assuming species
      equilibrium in the ELISA system and compared with apparent inhibition curves
      generated using the nominal concentration as the dose-metric. Because ligand
      binding to estrogen receptors may reduce its free concentration in the assay
      system, the differences between the two curves for free and nominal
      concentrations are more significant for more strongly binding ligands. The ratio
      of a compound's nominal concentration causing 50% inhibition (IC50) to the IC50
      of DES, the positive control, was strongly affected by specific assay conditions,
      while that estimated by modeling free concentration is independent of receptor
      concentration, indicating that the free concentration is a better dose-metric for
      a competitive binding assay.

PMID- 17559907
TI  - Environmental impacts of urban snow management--the alpine case study of
      Innsbruck.
AB  - In regions with colder climate, snow at roads can accumulate significant amounts
      of pollutant chemicals. In northern countries various efforts have been made to
      face this problem, but for the alpine region little is known about the pollution
      of urban snow. The present case study was carried out in the city of Innsbruck
      (Austria). It aimed at measuring pollution of roadside snow and estimating the
      impact of snow management practises on environmental quality. Concentrations of
      copper, zinc, lead, cadmium, suspended solids and chloride were determined during
      a series of sampling events. Various locations with low and high traffic
      densities and in different distances from a highway have been investigated. The
      concentrations of copper were generally higher at sites with high traffic density
      compared to locations with low traffic impact. In contrast to this, the
      concentrations of zinc and lead remained almost unvaried irrespective of traffic
      density at the different sampling sites. For cadmium, the picture was more
      diverse, showing moderately elevated concentrations of this metal also at the
      urban reference site not polluted by traffic. This indicates that there may be
      also other important sources for cadmium besides traffic. Suspended solids
      accumulated in the roadside snow, the highest concentrations were found at the
      sites with high traffic density. The chloride concentrations were considerable in
      the snow, especially at the highway. Based on the results of the present
      measurement campaign, the environmental impact of snow disposal in rivers was
      also estimated. A negative impact on rivers from snow disposal seems likely to
      occur, although the discharged loads could only be calculated with substantial
      uncertainty, considering the high variability of the measured pollutant
      concentrations. For a more accurate evaluation of this management practise on
      rivers, further investigations would be necessary.

PMID- 17559908
TI  - Assessing aspirin responsiveness using the Verify Now Aspirin assay.

PMID- 17559909
TI  - Matrix metalloproteinases-2, -3 and -9 in human term placenta.
AB  - Matrix metalloproteinases (MMPs) are zinc-dependent enzymes that degrade the
      components of the extracellular matrix (ECM) and are known to be the main
      mediators of human placentation and parturition. Although there are many studies
      on the roles and distribution of MMPs in human term placenta, so far none of the
      studies has investigated the distribution of MMP-2, -3 and -9 in different cells
      of various placental sites. In this study, we aimed to determine the distribution
      and enzymatic activities of MMP-2, -3 and -9 with regard to different regions of
      term human placenta, such as amnion, basal plate, chorionic plate, decidua,
      chorion laeve, Nitabuch's stria, umbilical cord and placental villi. Eighteen
      normal human term placentas were obtained after vaginal deliveries.
      Immunohistochemistry and zymography were performed for MMP-2, -3 and -9 on
      placental tissue sections and protein extracts, respectively. Nearly all tissues
      showed immunoreactivity for MMPs. The strongest enzymatic activity for MMP-2 was
      seen in areas where invasive trophoblast cells invaded maternal tissues. MMP-9
      had the highest enzymatic activity at the contact region of fetal and maternal
      parts, suggesting the importance of MMP-9 in separation of the placenta from the
      uterine wall during labor. MMP-3 had a similar localization to MMP-9, suggesting
      that besides gelatinases like MMP-2 and -9, MMP-3 (stromelysin-1) may also have
      important roles during labor. This study describes the site-specific distribution
      and activities of MMPs and therefore might help in elucidating the molecular
      mechanisms in pathologies such as premature rupture of membranes.

PMID- 17559910
TI  - Effect of histone deacetylase inhibitors on the cell nucleus and nucleolus of
      leukemic myeloblasts in vitro - a cytochemical study.
AB  - The present study was designed to provide complementary information on the
      effects of histone deacetylase inhibitors (HDACi's) such as trichostatin A (TSA)
      and sodium valproate (VAP) on nuclei and nucleoli of leukemic myeloblasts
      represented by cultured Kasumi-1 cells. The number of apoptotic cells and bodies
      with characteristic chromatin condensation and fragmentation was greater after
      TSA treatment. However, in contrast to TSA, myeloblasts treated with VPA
      recovered and started to proliferate again. TSA-treated myeloblasts with a fine
      chromatin structure exhibited an intense phagocytosis of cell fragments. The
      decreased number and translocation of silver-stained proteins of nucleolus
      organiser regions (AgNORs) in large nucleoli of myeloblasts treated with HDACi's
      indicated that these cells entered apoptosis and/or ageing without preceding
      terminal maturation. The nucleolar asynchrony observed in an increased number of
      treated cells with both HDACi's studied here possibly represented myeloblasts
      resistant to such treatment. In conclusion, this study demonstrates that the
      chromatin structure and nucleoli visualised by simple cytochemical procedures
      provides useful information on the effects of HDACi's on myeloblasts and
      facilitated detection of these effects at the single cell level.

PMID- 17559911
TI  - VEGF- and LPA-induced telomerase in human ovarian cancer cells is Sp1-dependent.
AB  - OBJECTIVE: Both vascular endothelial growth factor (VEGF) and lysophosphatidic
      acid (LPA) are secreted by ovarian cancer cells and are known to promote cancer
      cell growth though the exact mechanism(s) are not completely understood. Since
      telomerase, a ribonucleprotein expressed in 95% of ovarian cancers, plays an
      important role in cellular immortalization, growth, and tumor progression, we
      examined whether telomerase is a molecular target of LPA and VEGF in ovarian
      cancer. METHODS: Telomerase-positive ovarian carcinoma cell lines PA-1, SW 626,
      and one telomerase-negative, non-tumorigenic SV40 large-T antigen-transfected
      human ovarian surface epithelial (IOSE) cell line, FHIOSE 118, derived from
      normal ovarian surface epithelium were cultured with and without VEGF and LPA for
      4 h and 24 h, respectively. Telomerase PCR-ELISA, RT-PCR, VEGF ELISA and
      luciferase assays were performed to determine the effect of VEGF and LPA on
      telomerase activity in ovarian cancer cells. Western blot analyses were used to
      examine the signaling pathway involved in telomerase regulation by VEGF and LPA.
      RESULTS: We report that: (1) both VEGF and LPA upregulate telomerase activity;
      (2) LPA induction of telomerase activity is VEGF-dependent; (3) VEGF and LPA
      induction of telomerase activity is ERK 1/2-dependent; and (4) Sp1 binding sites
      within the proximal 976- to 378-bp regions of the hTERT promoter are essential
      for VEGF- and LPA-induced hTERT promoter activity. CONCLUSION: Consequently,
      these data show the novel finding that VEGF can regulate telomerase activity in
      non-endothelial cells and that telomerase appears to be a novel molecular target
      of LPA.

PMID- 17559912
TI  - Chymase-positive mast cells play a role in the vascular component of airway
      remodeling in asthma.
AB  - BACKGROUND: There is increasing evidence to support a role for total mast cells
      (MC(TOT)) in the vascular component of airway remodeling in asthma. On the
      contrary, up to now, no study has addressed the role of chymase-positive mast
      cells (MC(TC)) in microvasculature changes. OBJECTIVE: We sought to assess the
      role of MC(TC) in the vascular component of airway remodeling in asthma. METHODS:
      We recruited 8 patients with mild-to-moderate asthma and 8 healthy volunteers as
      a control group. Fiberoptic bronchoscopy with endobronchial biopsy was
      successfully performed in all subjects. Immunostaining was performed for
      quantification of vessels, vascular endothelial growth factor (VEGF)-positive
      cells, MC(TOT), and MC(TC). RESULTS: Compared with those from healthy subjects,
      endobronchial biopsy specimens from asthmatic patients showed increased numbers
      of MC(TOT) and MC(TC) and VEGF(+) cells (P < .05). In asthmatic patients the
      number of vessels and the vascular area was also greater than in healthy subjects
      (P < .05). Additionally, in asthmatic patients the number of MC(TC) was
      significantly related to the vascular area (r(s) = 0.74, P < .01) and to the
      number of VEGF(+) cells (r(s) = 0.78, P < .01). Moreover, a colocalization study
      revealed that MC(TC) were a relevant cellular source of VEGF. Finally, a 6-week
      treatment with inhaled fluticasone propionate was able to reduce MC(TC) numbers.
      CONCLUSION: MC(TC) can play a role in the vascular component of airway remodeling
      in asthma, possibly through induction of VEGF. CLINICAL IMPLICATIONS: Specific
      targeting of MC(TC) might be a tool for treating vascular remodeling in asthma.

PMID- 17559913
TI  - Critical role of kallikrein in hereditary angioedema pathogenesis: a clinical
      trial of ecallantide, a novel kallikrein inhibitor.
AB  - BACKGROUND: Hereditary angioedema (HAE) is a rare, autosomal-dominant disorder
      caused by C1 inhibitor gene mutation. Patients with HAE experience intermittent
      attacks of edema affecting the oropharynx, abdomen, gastrointestinal tract, and
      limbs. C1 inhibitor is the primary endogenous inhibitor of the kallikrein-kinin
      (contact) cascade. Unregulated kallikrein activation generates bradykinin, the
      likely mediator of the swelling and pain characterizing HAE attacks. Ecallantide,
      a novel, recombinant protein, potently inhibits kallikrein. This is the first
      placebo-controlled assessment in human beings of a therapeutic intervention to
      improve symptoms of HAE attacks under the hypothesis that the contact cascade is
      the putative pathway responsible for HAE pathology. OBJECTIVE: To determine the
      safety and efficacy of ecallantide in patients with HAE. METHODS: This double
      blind, placebo-controlled, ascending-dose study assessed efficacy and
      tolerability of ecallantide (5, 10, 20, or 40 mg/m(2) intravenously) in
      individuals experiencing acute HAE attacks (N = 49). Twelve patients were
      assigned to each dose level: 10 to ecallantide and 2 to placebo, per cohort.
      RESULTS: Ecallantide treatment ameliorated the symptoms of HAE attacks: 72.5%
      (29/40) of patients treated with ecallantide versus 25.0% (2/8) of placebo
      patients reported significant improvement in symptoms within 4 hours (P = .0169).
      Ecallantide was well tolerated at all doses. CONCLUSION: Ecallantide, a potent,
      specific inhibitor of plasma kallikrein, significantly improved HAE symptoms over
      placebo. The trial provides strong support for the role of the kallikrein-kinin
      cascade and its end product, bradykinin, in the pathophysiology of HAE. Further
      clinical trials are underway. CLINICAL IMPLICATIONS: Ecallantide is a promising
      new therapy for HAE attacks.

PMID- 17559914
TI  - Modulating leukocyte recruitment in inflammation.
AB  - Much information has been obtained regarding how white cells are recruited in the
      microcirculation to sites of inflammation. In this review we summarize the
      leukocyte recruitment cascade, highlighting the molecular mechanisms that
      underlie each of the major steps. Major emphasis is placed on the selectins and
      integrins and their role in rolling and adhesion. Intraluminal crawling and
      emigration are also briefly discussed. In addition, we summarize some of the data
      that implicate these molecules in eosinophil recruitment in animal models of
      asthma and in lymphocyte recruitment in skin contact sensitivity. There is a
      growing body of evidence to suggest that leukocyte recruitment could be used as
      an effective means for future therapeutics, and some of these issues are also
      raised.

PMID- 17559915
TI  - IgE-mediated allergy to chlorhexidine.
AB  - BACKGROUND: Investigations at the Danish Anesthesia Allergy Centre have included
      testing for allergy to chlorhexidine since 1999. OBJECTIVE: To investigate
      whether measurement of IgE and histamine release confirm an IgE-mediated
      mechanism for chlorhexidine allergy. METHODS: Twenty-two patients with clinical
      history suggestive of chlorhexidine allergy were included. Skin tests with
      chlorhexidine and tryptase measurements were performed during initial
      investigations. Sera were analyzed retrospectively for IgE and histamine release
      (passive sensitization) to chlorhexidine. RESULTS: Twelve patients were skin test
      positive and 10 were skin test negative. Of the skin test-positive patients, 11
      of 12 had IgE to chlorhexidine and 7 of 11 had a positive histamine release test.
      None of the skin test-negative patients had specific IgE or positive histamine
      release to chlorhexidine. Skin test-positive patients had higher median age (64
      vs 49 y) and were mainly male (11/12 vs 6/10). In both groups, 8 patients had
      hypotension, but bronchospasm mainly appeared in skin test-negative patients
      (1/12 vs 6/10). Reactions occurred more often during urologic surgery in skin
      test-positive patients (5/12 vs 0/10). Baseline tryptase was higher in skin test
      positive patients (median, 11.5 vs 3.7 microg/L), and 6 of 7 patients had
      elevated IgE to chlorhexidine in serum at the time of reaction. CONCLUSION: This
      study confirms that chlorhexidine allergy is IgE-mediated and that measurement of
      specific IgE and histamine release are good adjuncts to skin testing in patients
      with clinical history suggesting chlorhexidine allergy. CLINICAL IMPLICATIONS:
      IgE and histamine release can be used to support the diagnosis of allergy to
      chlorhexidine.

PMID- 17559916
TI  - Regional differences in EpiPen prescriptions in the United States: the potential
      role of vitamin D.
AB  - BACKGROUND: The epidemiology of anaphylaxis is uncertain, especially its
      geographic distribution. OBJECTIVE: To address this deficit, we examined regional
      rates of EpiPen prescriptions in the United States. METHODS: EpiPen prescriptions
      in 2004 were obtained for all 50 states and Washington, DC, from NDCHealth,
      Pharmaceutical Audit Suite (Alpharetta, Ga). Data included the number of total
      filled prescriptions, including refills, and the actual number of EpiPens
      prescribed. Several data sets were used to obtain state-specific populations, as
      well as multiple demographic, health, and weather characteristics. State
      population was used to calculate the average number of prescriptions written per
      person. RESULTS: Overall, there were 1,511,534 EpiPen prescriptions filled during
      2004. These prescriptions accounted for 2,495,188 EpiPens. On average, there were
      5.71 EpiPens prescribed per 1000 persons. Massachusetts had the highest number of
      prescriptions per 1000 persons (11.8), whereas Hawaii had the lowest (2.7). In
      addition to state-to-state variation, there was an obvious regional difference:
      New England (Connecticut, Rhode Island, Massachusetts, Vermont, New Hampshire,
      Maine) had the highest values, with 8 to 12 EpiPen prescriptions per 1000
      persons, whereas the southern states (between and including California and
      Mississippi) had only 3 prescriptions per 1000 persons. The New England finding
      persisted even when controlling for all available factors (eg, population
      demographic characteristics, number of health care providers, prescriptions for
      other medications). CONCLUSION: A strong north-south gradient was observed for
      the prescription of EpiPens in the United States, with the highest rates found in
      New England. CLINICAL IMPLICATIONS: The regional differences in EpiPen
      prescribing may provide important etiologic clues (vitamin D status) and merit
      further investigation.

PMID- 17559917
TI  - Missed opportunities for the prevention of influenza.

PMID- 17559918
TI  - CHIC--the Canine Health Information Center.
AB  - The Canine Health Information Center (CHIC) is a centralized canine health
      database, jointly sponsored by the Orthopedic Foundation for Animals (OFA) and
      the AKC Canine Health Foundation (AKC CHF). The CHIC mission is to provide a
      source of health information for owners, breeders, and scientists that will
      assist in breeding healthier dogs. Dogs are issued CHIC numbers when there are
      tested in accordance with the health screening protocol established by their
      parent club. All CHIC results are available in an online publicly accessible
      database, so the results can be widely utilized in making more informed breeding
      decisions. CHIC also operates a DNA bank which stores canine DNA samples along
      with corresponding genealogic information and phenotypic health data. These
      samples are made available to the research community at large for canine health
      research purposes to facilitate the sample collection process and provide
      optimized family groups.

PMID- 17559919
TI  - Challenges in small animal parturition--timing elective and emergency cesarian
      sections.
AB  - Given the societal emphasis placed on the deliberate breeding of purebred
      animals, the practitioner today is faced with issues relative to successful
      parturition in these animals. Today, the serious hobby breeder expects to use
      planned breeding management to result in a high conception and pregnancy rate and
      survival rates of offspring that may exceed published parameters. These clients
      may elect to schedule cesarean section to maximize puppy survival and assure that
      they have access to quality veterinary care. Using a combination of hormone
      assays, temperature changes in the dam and carefully timed and documented
      breeding management, a cesarean section can be planned. Emergency cesarean
      sections will still be required for the bitch that experiences dystocia or a
      medical condition that warrants intervention. Timed cesarean section results in a
      favorable medical outcome for the dam and litter and a better financial outcome
      for the owner.

PMID- 17559920
TI  - The antifreeze protein type I (AFP I) increases seabream (Sparus aurata) embryos
      tolerance to low temperatures.
AB  - To date, all attempts at fish embryo cryopreservation have failed. One of the
      main reasons for this to occur is the high chilling sensitivity reported in fish
      embryos thus emphasizing the need for further testing of different methods and
      alternative cryoprotective agents (CPAs) in order to improve our chances to
      succeed in this purpose. In this work we have used the antifreeze protein type I
      (AFP I) as a natural CPA. This protein is naturally expressed in sub-arctic fish
      species, and inhibits the growth of ice crystals as well as recrystallization
      during thawing. Embryos from Sparus aurata were microinjected with AFP I at
      different developmental stages, 2 cells and blastula, into the blastomere-yolk
      interface and into the yolk sac, respectively. Control, punctured and
      microinjected embryos were subjected to chilling at two different temperatures, 0
      degrees C (1h) and -10 degrees C (15min) when embryos reached 5-somite stage.
      Embryos were subjected to -10 degrees C chilling in a 3M DMSO extender to avoid
      ice crystal formation in the external solution. Survival after chilling was
      established as the percentage of embryos that hatch. To study the AFP I
      distribution in the microinjected embryos, a confocal microscopy study was done.
      Results demonstrate that AFP I can significantly improve chilling resistance at 0
      degrees C, particularly in 2-cell microinjected embryos, displaying nearly 100%
      hatching rates. This fact is in agreement with the confocal microscopy
      observations which confirmed the presence of the AFP protein in embryonic cells.
      These results support the hypothesis that AFP protect cellular structures by
      stabilizing cellular membranes.

PMID- 17559921
TI  - Semen of Perca fluviatilis L.: sperm volume and density, seminal plasma indices
      and effects of dilution ratio, ions and osmolality on sperm motility.
AB  - The objectives of the present study were to characterize sperm volume and
      density, seminal plasma indices (ionic contents and osmolality) and to study the
      effects of dilution ratio, ions and osmolality on sperm motility parameters
      (percentage of motile sperm and sperm velocity) in farmed European perch (Perca
      fluviatilis L.). The means of sperm volume (ml), sperm density (x10(9)spermml(
      1)) and total number of sperm (volumexdensity) per fish were 2.75+/-0.51, 29.19+/
      3.15 and 82.19+/-15.26. The seminal plasma osmolality (mOsmkg(-1)), sodium,
      chloride, potassium and calcium ions concentrations (mM) were measured to be
      298.07+/-5.09, 130.97+/-2.19, 106.75+/-2.37, 10.70+/-0.61 and 2.41+/-0.09,
      respectively. At 15s post-activation of stripped sperm, the percentage of motile
      sperm (%) and sperm velocity (mums(-1)) were 91.90+/-1.27 and 115.54+/-1.25,
      respectively, and decreased significantly following sperm activation (P<0.05).
      The optimal sperm motility was observed when the sperm was prediluted in
      immobilizing solution (IS) at a ratio 1:50. Prediluted sperm showed the maximum
      velocity when activated in 2.5mM Ca(2+), 50mM K(+) and sucrose with osmolality
      100mOsmkg(-1). Neither Ca(2+) nor K(+) showed a significant effect on the
      percentage of motile sperm at 15s post-activation. Osmolality higher than
      200mOsmkg(-1) significantly decreased the percentage of motile sperm, while
      osmolality of 300mOsmkg(-1) or above totally suppressed sperm motility.

PMID- 17559922
TI  - Expression pattern of oxygen and stress-responsive gene transcripts at various
      developmental stages of in vitro and in vivo preimplantation bovine embryos.
AB  - The present study examined the expression pattern of oxygen (O(2)) and stress
      responsive gene transcripts at various preimplantation developmental stages of in
      vitro produced (IVP) and in vivo derived (IVD) bovine embryos. Embryos were
      produced in vitro from oocytes matured, fertilized and cultured in synthetic
      oviductal fluid (SOF) medium under low (5%) and high (20%) O(2) concentrations.
      In vivo embryos were derived from 18 superovulated and artificially inseminated
      cows. In IVP and IVD groups, embryos were collected at 2-, 4-, 8-, 16-cell morula
      and blastocyst stages at specific time points for gene expression analysis. The
      cleavage rates (69.8+/-4.8%) did not differ significantly, but blastocyst rates
      were significantly higher (28.5+/-3.7%) in low O(2) than those in high O(2) group
      (18.7+/-3.9%). Mean cell number in low O(2) (145+/-12) and high O(2) (121+/-73)
      IVP blastocyst were lower (P<0.05) than those of IVD blastocyst (223+/-25). The
      ICM ratio of IVD blastocyst (26+/-4) was lower (P<0.05) than that of IVP embryos
      under 5% O(2) (33+/-5) and 20% O(2) (34+/-4) concentrations, respectively. Using
      real time PCR, for the set of target transcripts (Glut1, Glut5, Sox, G6PD, MnSOD,
      PRDX5, NADH and Hsp 70.1) analyzed, there were differences in the mRNA expression
      pattern at 2-, 4-, 8-, 16-cell morula and Day 7 blastocyst stages between the two
      embryo sources. It can be concluded that, although in vitro bovine embryo culture
      in SOF medium under low (5%) O(2) concentration provided a more conducive
      environment in terms of blastocyst formation; differences in the total cell
      number and gene expression pattern between the IVP and IVD embryos reflected the
      effect of O(2) concentration.

PMID- 17559923
TI  - The effect of skin allografting on the equine endometrial cup reaction.
AB  - This research tested the hypothesis that immunological sensitization of mares by
      skin allografting, followed by the establishment of pregnancy using semen from
      the skin-graft donor, would give rise to secondary immune responses to the
      developing horse conceptus, resulting in an earlier demise of the fetally derived
      endometrial cups. Maiden mares received skin allografts from a stallion
      homozygous for Major Histocompatibility Complex (MHC) antigens and/or equivalent
      autografts and were subsequently mated to the skin-graft donor stallion during
      the next two breeding seasons. Mares that had been immunologically primed to the
      foreign MHC class I antigens of the skin-graft donor stallion developed strong
      secondary antibody responses early in their first pregnancies, whereas
      autografted mares made weak primary antibody responses in their first pregnancies
      and strong secondary responses in their second pregnancies. In contrast,
      histological examination of the endometrial cups after surgical pregnancy
      termination at Day 60 of gestation revealed no discernible differences between
      allografted and autografted mares, and there were no significant differences in
      the concentrations and/or duration of secretion of the endometrial cup-specific
      hormone, equine chorionic gonadotrophin (eCG), between allografted and
      autografted mares, nor in either group between first and second pregnancies. The
      vigorous antibody response observed in the pregnant allografted mares supported
      the first part of our hypothesis, providing evidence of systemic immunological
      priming. However, there was a lack of an equivalent heightened cellular response
      to the endometrial cups. These findings provided strong evidence for an
      asymmetric immune response to the conceptus, characterized by strong humoral
      immunity and a dampened cellular response.

PMID- 17559924
TI  - Respiration rates correlate with mRNA expression of G6PD and GLUT1 genes in
      individual bovine in vitro-produced blastocysts.
AB  - Quantification of embryo respiration is a promising procedure to assess embryonic
      metabolism and possibly select viable embryos. At the blastocyst stage, ATP is
      produced by glycolysis and oxidative phosphorylation, processes that require
      uptake of oxygen and glucose, which is regulated by the expression of GLUT1 and
      G6PD. The purpose of the present study was to investigate the relationship
      between respiration rates and relative abundances of G6PD and GLUT1 transcripts
      in individual bovine blastocysts produced in vitro. Respiration rates of 104
      bovine in vitro-produced blastocysts were measured individually using the
      nanorespirometer technology. Real-time RT-PCR was employed to determine the
      relative abundance of G6PD and GLUT1 mRNA in individual embryos. The mean
      respiration rates were similar for male and female blastocysts of the same
      developmental stage, but the sex ratio was skewed towards males. GLUT1 expression
      was down-regulated in female versus male embryos. In contrast, a approximately
      1.8-fold increase in the expression of G6PD mRNA was observed in female
      blastocysts when compared to male blastocysts, indicating that dosage
      compensation for this gene had not yet occurred. Both GLUT1 and G6PD expression
      levels were affected by morphological quality and stage of development.
      Expression of GLUT1 and G6PD mRNAs was correlated with respiration rates,
      indicating that, in metabolically active blastocysts, uptake of oxygen and
      glucose are jointly increased. These findings suggest that expression of genes
      for oxidative phosphorylation and glycolysis are both involved in oxygen
      demanding ATP production.

PMID- 17559925
TI  - Intratesticular injection of a zinc-based solution as a contraceptive for dogs.
AB  - The objective of the present study was to evaluate, by light and transmission
      electron microscopy, the efficacy of a single intratesticular injection of a
      novel zinc-based solution, as a contraceptive for male dogs. Fifteen mongrel dogs
      were assigned to three groups (five dogs/group). Group 1, the control group,
      which consisted of animals ranging from 8 mo to 4 yr, was injected with saline
      solution. Group 2, which consisted of animals ranging from 8 mo to 1 yr old and
      Group 3, animals ranging from 2 to 4 yr old, were injected with a zinc-based
      solution (0.2-1.0mL; volume based on testicular width). There were no
      histopathological changes detected in testes from control dogs. Histological
      examination of treated groups revealed degeneration, vacuolation, fewer germ
      cells, formation of multinucleated giant cells, and a lack of elongated
      spermatids in atrophic seminiferous tubules. Leydig cells had varying degrees of
      lipid degeneration and necrosis. The majority of seminiferous tubules in all zinc
      treated dogs were lined only by Sertoli cells, which were vacuolated.
      Ultrastructure of testis of treated groups had degenerate Sertoli and Leydig
      cells, characterized by numerous mitochondria with the lack of a matrix and
      agglomeration of lysosomal bodies. The cytoplasm of elongated spermatids was
      characterized by tubules of hyperplastic and hypertrophic smooth endoplasmic
      reticulum and numerous Golgi apparati. Round spermatids in Golgi phase had lysis
      of acrosomal vesicles. The degree of histological changes suggested
      irreversibility. In conclusion, intratesticular injection of a zinc-based
      solution effectively impaired spermatogenesis.

PMID- 17559926
TI  - Effect of cyclic loading under enzymatic activity on resin-dentin interfaces of
      two self-etching adhesives.
AB  - OBJECTIVES: To evaluate microtensile bond strength and micro-morphology at the
      resin-dentin interfaces of two self-etching adhesive systems subjected to
      simultaneous mechanical and enzymatic stress. METHODS: Sixteen enamel/dentin
      discs were bonded with a two-step self-etching adhesive (AdheSE, n=8) and a one
      step self-etching adhesive (Xeno III, n=8) to a 2mm thick resin composite layer.
      One resin-dentin bar was obtained per tooth. In half of the specimens of each
      group microTBS and micro-morphological evaluations (TEM) was performed without
      loading. The other half was mechanically loaded in a cholinesterase-containing
      solution. MicroTBS as well as ultra-morphological evaluations of the directly
      loaded areas using TEM were performed on the loaded specimens. RESULTS: The
      microTBS of the specimens (non-loaded/loaded) were of 39.6+/-14.7/35.4+/-22.1 and
      of 21.8+/-29.8/15.9+/-25.5 for AdheSE and Xeno III, respectively. Under TEM, both
      materials presented signs of nanoleakage. However, on loaded specimens the extent
      of nanoleakage was slightly reduced for AdheSE and no silver staining was
      observed on the adhesive interface of Xeno III. TEM evaluations of the specimens'
      loaded area revealed no decrease in the width of the adhesive interface for
      AdheSE. The contrary was observed in the interface created by Xeno III.
      SIGNIFICANCE: The adhesive interfaces created by the two-step self-etching
      adhesive (AdheSE) could better withstand both mechanical and enzymatic stresses
      on the long-term than the one-step self-etching system (Xeno III) tested in the
      present study.

PMID- 17559927
TI  - Brief report: Coping among Austrian children and adolescents.
AB  - The study investigated age and gender effects on coping with common stressors
      among 494 Austrian children and adolescents (age 8-14 years). Participants were
      subdivided into subgroups of late children comprising third and fourth graders,
      early adolescents consisting of fifth and sixth graders, and middle adolescents
      including seventh graders. Middle adolescents showed a maladaptive coping pattern
      with decreased problem and emotion-focused coping strategies and increased
      passive avoidance and aggression. Females scored higher on social support and
      also on the maladaptive coping strategy rumination. Female middle adolescents
      reported higher resignation than their male contemporaries and female children.
      Results suggest the application of primary preventive stress management programs
      in late childhood and early adolescence.

PMID- 17559928
TI  - The safety of statins in clinical practice.
AB  - Statins are effective cholesterol-lowering drugs that reduce the risk of
      cardiovascular disease events (heart attacks, strokes, and the need for arterial
      revascularisation). Adverse effects from some statins on muscle, such as myopathy
      and rhabdomyolysis, are rare at standard doses, and on the liver, in increasing
      levels of transaminases, are unusual. Myopathy--muscle pain or weakness with
      blood creatine kinase levels more than ten times the upper limit of the normal
      range--typically occurs in fewer than one in 10,000 patients on standard statin
      doses. However, this risk varies between statins, and increases with use of
      higher doses and interacting drugs. Rhabdomyolysis is a rarer and more severe
      form of myopathy, with myoglobin release into the circulation and risk of renal
      failure. Stopping statin use reverses these side-effects, usually leading to a
      full recovery. Asymptomatic increases in concentrations of liver transaminases
      are recorded with all statins, but are not clearly associated with an increased
      risk of liver disease. For most people, statins are safe and well-tolerated, and
      their widespread use has the potential to have a major effect on the global
      burden of cardiovascular disease.

PMID- 17559929
TI  - Antenatal dexamethasone treatment leads to changes in gene expression in a murine
      late placenta.
AB  - Antenatal steroids like dexamethasone (DEX) are used to augment fetal lung
      maturity and there is a major concern that they impair fetal growth. If delivery
      is delayed after using antenatal DEX, placental function and hence fetal growth
      may be compromised even further. To investigate the effects of DEX on placental
      function, we treated 9 pregnant C57/BL6 mice with DEX and 9 pregnant mice were
      injected with saline to serve as controls. Placental gene expression was studied
      using microarrays in 3 pairs and other 6 pairs were used to confirm microarray
      results by semi-quantitative RT-PCR, real-time PCR, in situ hybridization,
      western blot analysis and Oligo ApopTaq assay. DEX-treated placentas were
      hydropic, friable, pale, and weighed less (80.0+/-15.1mg compared to 85.6.8+/
      7.6mg, p=0.05) (n=62 placentas). Fetal weight was significantly reduced after DEX
      use (940+/-32mg compared to 1162+/-79mg, p=0.001) (n=62 fetuses). There was >99%
      similarity within and between the three gene chip data sets. DEX led to down
      regulation of 1212 genes and up-regulation of 1382 genes. RT-PCR studies showed
      that DEX caused a decrease in expression of genes involved in cell division such
      as cyclins A2, B1, D2, cdk 2, cdk 4 and M-phase protein kinase along with growth
      promoting genes such as EGF-R, BMP4 and IGFBP3. Oligo ApopTaq assay and western
      blot studies showed that DEX-treatment increased apoptosis of trophoblast cells.
      DEX-treatment led to up-regulation of aquaporin 5 and tryptophan hydroxylase
      genes as confirmed by real-time PCR, and in situ hybridization studies. Thus
      antenatal DEX treatment led to a reduction in placental and fetal weight, and
      this effect was associated with a decreased expression of several growth
      promoting genes and increased apoptosis of trophoblast cells.

PMID- 17559930
TI  - In vitro differentiation of villous trophoblasts from pregnancies complicated by
      intrauterine growth restriction with and without pre-eclampsia.
AB  - Highly purified (>99.99%) primary villous cytotrophoblasts from uncomplicated
      pregnancies and pregnancies complicated with intrauterine growth restriction
      (IUGR) alone, IUGR with pre-eclampsia (IUGR-PE) and PE alone were cultured for
      5days and the extent of differentiation into syncytiotrophoblasts measured in
      terms of syncytialisation and secretion of chorionic gonadotropin (hCG) and
      placental lactogen (hPL). Three separate phenotypes were observed: (1) normal and
      IUGR-PE cells showed low syncytialisation and secretion of hCG and hPL, (2) IUGR
      cells showed the highest levels of syncytialisation and secretion and (3) PE
      cells showed high syncytialisation but low secretion. These results strongly
      suggest IUGR, IUGR-PE and PE to be distinct conditions in which villous
      cytotrophoblasts are either exposed to different environments or are genetically
      different.

PMID- 17559931
TI  - Metabotropic Ca2+ channel-induced calcium release in vascular smooth muscle.
AB  - Contraction of vascular smooth muscle cells (VSMCs) depends on the rise of
      cytosolic [Ca(2+)] owing to either Ca(2+) influx through voltage-gated Ca(2+)
      channels of the plasmalemma or to receptor-mediated Ca(2+) release from the
      sarcoplasmic reticulum (SR). Although the ionotropic role of L-type Ca(2+)
      channels is well known, we review here data suggesting a new role of these
      channels in arterial myocytes. After sensing membrane depolarization Ca(2+)
      channels activate G proteins and the phospholipase C/inositol 1,4,5-trisphosphate
      (InsP(3)) pathway. Ca(2+) released through InsP(3)-dependent channels of the SR
      activates ryanodine receptors to amplify the cytosolic Ca(2+) signal, thus
      triggering arterial cerebral vasoconstriction in the absence of extracellular
      calcium influx. This metabotropic action of L-type Ca(2+) channels, denoted as
      calcium channel-induced Ca(2+) release, could have implications in cerebral
      vascular pharmacology and pathophysiology, because it can be suppressed by Ca(2+)
      channel antagonists and potentiated with small concentrations of extracellular
      vasoactive agents as ATP.

PMID- 17559933
TI  - Liking vs. wanting food: importance for human appetite control and weight
      regulation.
AB  - Current train of thought in appetite research is favouring an interest in non
      homeostatic or hedonic (reward) mechanisms in relation to overconsumption and
      energy balance. This tendency is supported by advances in neurobiology that
      precede the emergence of a new conceptual approach to reward where affect and
      motivation (liking and wanting) can be seen as the major force in guiding human
      eating behaviour. In this review, current progress in applying processes of
      liking and wanting to the study of human appetite are examined by discussing the
      following issues: How can these concepts be operationalised for use in human
      research to reflect the neural mechanisms by which they may be influenced? Do
      liking and wanting operate independently to produce functionally significant
      changes in behaviour? Can liking and wanting be truly experimentally separated or
      will an expression of one inevitably contain elements of the other? The review
      contains a re-examination of selected human appetite research before exploring
      more recent methodological approaches to the study of liking and wanting in
      appetite control. In addition, some theoretical developments are described in
      four diverse models that may enhance current understanding of the role of these
      processes in guiding ingestive behaviour. Finally, the implications of a dual
      process modulation of food reward for weight gain and obesity are discussed. The
      review concludes that processes of liking and wanting are likely to have
      independent roles in characterising susceptibility to weight gain. Further
      research into the dissociation of liking and wanting through implicit and
      explicit levels of processing would help to disclose the relative importance of
      these components of reward for appetite control and weight regulation.

PMID- 17559932
TI  - Growth and reproduction of the earthworm Eisenia fetida after exposure to
      leachate from wood preservatives.
AB  - Wood preserved with chromated copper arsenate (CCA) and alkaline copper
      quaternary (ACQ) was mixed with artificial rainwater, to generate leachates
      containing As, Cr and Cu. Then, leachates were applied to two soils at rates of
      13-169 mg As kg(-1) soil (dry weight basis), 12-151 mg Cr kg(-1) and 10-216 mg Cu
      kg(-1). Metal bioavailability was evaluated after 28 days using the earthworm
      Eisenia fetida (Savigny). Metal concentrations in earthworm tissue ranged from
      negligible to 80 mg As kg(-1) (dry weight basis), 89 mg Cr kg(-1) and 90 mg Cu
      kg(-1), which appeared to be non-lethal to E. fetida. There was less Cu available
      to earthworms in the Courval soil (pH 7.8) than the Chateauguay soil (pH 6.8),
      but earthworm growth and reproduction were not affected by exposure to Cu from
      ACQ-treated wood. In contrast, earthworms exposed to As, Cr and Cu from the CCA
      treated wood gained weight more quickly in the Courval soil (1.3-21 mg g(-1)
      initial biomass days) than in the Chateauguay soil (0.2-7.8 mg g(-1) day(-1)),
      but fewer than 20% of the cocoons deposited by the faster-growing earthworms
      hatched by the end of the 56 days ecotoxicology test. It appeared that E. fetida
      can allocate more energy to growth than reproduction, delaying cocoon development
      and hatching in some situations. Further information is needed on the soil
      factors that may induce such behavior, as it can affect the interpretation of
      results from the earthworm ecotoxicology test.

PMID- 17559935
TI  - Natural and synthetic endocrine disrupting compounds (EDCs) in water, sediment
      and biota of a coastal lagoon.
AB  - We report a survey on the occurrence and distribution of natural (17beta
      estradiol, E2; estrone, E1) and synthetic (nonylphenol, NP; nonylphenol
      monoethoxylate carboxylate, NP1EC; bisphenol-A, BPA; benzophenone, BP; mestranol,
      MES; 17alpha-ethinylestradiol, EE2; diethylstilbestrol, DES) endocrine disrupting
      compounds (EDCs) in water, sediment and biota (Mediterranean mussel, Mytilus
      galloprovincialis) in the Venice lagoon, a highly urbanized coastal water
      ecosystem that receives both industrial and municipal wastewater effluents. The
      survey was preceded by the development of tailor made extraction and clean-up
      procedures for the simultaneous HPLC-ESI-MS determination of all examined EDCs in
      sediment and biota samples. Satisfactory extraction performances and method
      detection limits (MDLs) were obtained for almost all EDCs. Most of the selected
      compounds were found in water and sediment (concentration range: 2.8-211 ng/L,
      and 3.1-289 microg/kg, d.w., respectively), while only 17alpha-ethinylestradiol
      and nonylphenol were recorded in biota samples (conc. range: 7.2-240 ng/g, d.w.).
      17beta-estradiol and ethinylestradiol contributed mostly to the water estradiol
      equivalent concentration (EEQ) (1.1-191 ng/L, average: 25 ng/L), while synthetic
      EDCs (17alpha-ethinylestradiol, diethylstilbestrol) were mainly responsible of
      the sediment EEQ (1.1-191 microg/kg, average: 71 microg/kg, d.w.). Whenever
      diethylstilbestrol was not recorded in the sediment, water EEQs were similar to
      sediment EEQs. A remarkable increase of nonylphenol was observed in sediments
      over the last decade.

PMID- 17559936
TI  - Molecular cloning and functional characterization of porcine nucleotide-binding
      oligomerization domain-2 (NOD2).
AB  - The nucleotide-oligomerization domain (NOD) 2 is an important molecule involved
      in host defense. In this study, we report the cloning and characterization of
      porcine NOD2 (poNOD2) cDNA. The open reading frame of poNOD2 contains 3042 bp
      which encode 1013 amino acid residues. The putative poNOD2 protein shares higher
      level of homology with human counterpart (81.6% amino acid identity) than the
      mouse protein (76.6% amino acid identity). In order to determine the function of
      poNOD2, we established human embryonic kidney (HEK) 293 cells transfected to
      express poNOD2 cDNA. We found that poNOD2 was expressed not only in the cytoplasm
      but also in the inner side of the plasma membrane of HEK293 cells. HEK293 cells
      expressing poNOD2 responded to muramyl dipeptide (MDP) by activation of the
      nuclear factor kappa B (NF-kappaB). Quantitative real-time PCR revealed that
      poNOD2 mRNA was expressed by a number of tissues isolated from adult and newborn
      swine such as esophagus, duodenum, jejunum, ileum, ileal Peyer's patches (Pps),
      colon, spleen, and mesenteric lymph nodes (MLNs). In the newborn swine, the
      expression of poNOD2 mRNA was detected at higher levels in MLNs and spleen as
      compared to other tissues. In the adult swine, the highest expression was
      observed in ileal Pps. Furthermore, Toll-like receptor (TLR) and NOD2 ligands as
      well as immunobiotic lactic acid bacteria (LAB) enhanced the expression of NOD2
      in gut-associated lymphoid tissues (GALT) in adult and newborn swine. Our results
      implicate NOD2 as an important immunoregulator in the swine intestinal immunity.

PMID- 17559937
TI  - Orbicularis muscle advancement flap combined with free posterior and anterior
      lamellar grafts: a 1-stage sandwich technique for eyelid reconstruction.
AB  - PURPOSE: To report on a new 1-stage technique for eyelid reconstruction. DESIGN:
      Retrospective interventional case series. PARTICIPANTS: Thirteen patients with
      shallow full-thickness lower eyelid defects (n = 12) or a full-thickness upper
      eyelid defect (n = 1) after tumor excision. Defect size ranged from 5 to 10 mm
      vertically and from 10 to 22 mm horizontally. METHODS: For eyelid reconstruction,
      the orbicularis muscle adjacent to the defect was mobilized, incised vertically,
      and advanced. The inner surface was covered with a free tarsoconjunctival graft
      from the (ipsilateral or contralateral) upper lid, and the outer surface was
      covered with a free skin graft from the (ipsilateral or contralateral) upper
      eyelid. MAIN OUTCOME MEASURES: The outcome at 12 months after surgery was
      assessed using a subjective scoring system with 4 subsequent grades (poor,
      adequate, good, excellent). RESULTS: After 5 days of patching, adequate viability
      of the grafts was noted in 11 of 13 patients. In 2 patients, partial necrosis of
      the skin graft developed, probably the result of hematoma. Complications included
      ectropion or lid retraction (3/13), granuloma (2/13), and notching (1/13). Two
      patients underwent additional block excision. The long-term outcome at 12 months
      after surgery was poor in 0 cases, adequate in 2 cases, good in 7 cases, and
      excellent in 4 cases. CONCLUSIONS: The sandwich technique for eyelid
      reconstruction comprises the use of an orbicularis oculi muscle advancement flap,
      which is covered with a free graft on both sides. It allows for 1-stage
      reconstruction of relatively shallow lower eyelid defects with a horizontal size
      of up to 70% of the total eyelid width and may be a 1-stage alternative to the
      modified Hughes flap in selected cases.

PMID- 17559938
TI  - Solution equilibria of copper(II) complexation with N,N'-(2,2'
      azanediylbis(ethane-2,1-diyl))dipicolinamide: a bio-distribution and dermal
      absorption study.
AB  - The protonation equilibria of a pentadentate ligand, N,N'-(2,2'
      azanediylbis(ethane-2,1-diyl))dipicolinamide ([H(2)(5555)-N]) and the
      complexation of this ligand with Cu(II) Ca(II), Zn(II) and Ni(II) have been
      studied by pH-potentiometry, (1)H NMR spectroscopy and UV-vis spectrophotometry.
      (1)H NMR detected the protonation of the pyridyl groups and formation of
      Cu[H(2)(5555)-N]H species at low pH, while amide group deprotonation at higher pH
      resulted in the formation of Cu[H(2)(5555)-N]H(-1) and Cu[H(2)(5555)-N]H(-2)
      species in solution. Potentiometric detection of protonated species was limited
      by the acidic nature of the pyridyl nitrogen donors. From UV-vis spectroscopy it
      is suggested that the amide nitrogens are coordinated. This conclusion is
      supported by Molecular Mechanics calculations. Water-octanol partition
      coefficients for the Cu(II)-[H(2)(5555)-N] system indicated that although the
      Cu[H(2)(5555)-N]H(-1) species is largely hydrophilic, approximately 54% of the
      complex goes into the organic phase. This percentage is able to promote dermal
      absorption of copper with a calculated penetration rate of 1.92x10(-1)cmh(-1).
      This was confirmed by dermal absorption studies which illustrate the role of
      hydrophobicity in promoting percutaneous drug administration.

PMID- 17559939
TI  - A comparative analysis of tuberculous, brucellar and pyogenic spontaneous
      spondylodiscitis patients.
AB  - OBJECTIVE: This study aimed to compare clinical, laboratory, and radiological
      features of spontaneous spondylodiscitis secondary to tuberculosis and
      brucellosis, both of which are endemic in Turkey, and spondylodiscitis due to
      other bacterial causes (pyogenic spondylodiscitis) and to provide guidance for
      clinicians in determining causative agents of spondylodiscitis. MATERIAL AND
      METHODS: This prospective study involved 75 patients diagnosed as
      spondylodiscitis. All the patients were divided into three groups: tuberculous
      spondylodiscitis (Group TS), brucellar spondylodiscitis (Group BS), and pyogenic
      spondylodiscitis (Group PS). RESULTS: Forty patients (53.3%) were male and 35
      (46.7%), female. The mean age of the patients was 57.8+/-14.8 years (17-82
      years). Group TS included 13 patients (17.3%), Group BS 32 patients (42.7%), and
      Group PS 30 patients (40%). A significantly higher rate of microorganisms was
      isolated and a significantly higher rate of high fever was determined in Group
      BS. Group TS had a significantly higher rate of accompanying chronic renal
      failure, constitutional symptoms, psoas abscess, history of tuberculosis, high
      sedimentation rate, involvement of posterior elements, and/or surgical treatment.
      CONCLUSION: The presence of back pain, fever, elevated inflammatory markers and a
      documented history of tuberculosis in association with radiological involvement
      of the posterior spinous elements is pathognomonic of tuberculous spinal
      infection, even in the absence of positive culture.

PMID- 17559941
TI  - High throughput quantification of cells with complex morphology in mixed
      cultures.
AB  - Automated image-based and biochemical assays have greatly increased throughput
      for quantifying cell numbers in in vitro studies. However, it has been more
      difficult to automate the counting of specific cell types with complex
      morphologies in mixed cell cultures. We have developed a fully automated, fast,
      accurate and objective method for the quantification of primary human GFAP
      positive astrocytes and CD45-positive microglia from images of mixed cell
      populations. This method, called the complex cell count (CCC) assay, utilizes a
      combination of image processing and analysis operations from MetaMorph (Version
      6.2.6, Molecular Devices). The CCC assay consists of four main aspects: image
      processing with a unique combination of morphology filters; digital thresholding;
      integrated morphometry analysis; and a configuration of object standards. The
      time needed to analyze each image is 1.82s. Significant correlations have been
      consistently achieved between the data obtained from CCC analysis and manual cell
      counts. This assay can quickly and accurately quantify the number of human
      astrocytes and microglia in mixed cell culture and can be applied to quantifying
      a range of other cells/objects with complex morphology in neuroscience research.

PMID- 17559942
TI  - No association between the tumor necrosis factor-alpha gene promoter
      polymorphisms and schizophrenia in a Japanese population.
AB  - Tumor necrosis factor-alpha (TNF-alpha) is a pleiotrophic cytokine and exerts
      neuroprotective and neurodegenerative effects in brain. Several studies have
      indicated that TNF-alpha is likely related to the pathogenesis of schizophrenia.
      Recent genetic investigations have revealed that a TNF-alpha gene promoter
      polymorphism (-G308A) is associated with schizophrenia, although negative
      findings have also been reported. To assess whether the TNF-alpha gene promoter
      variants including -G308A could be implicated in vulnerability to schizophrenia,
      we conducted a case-control association analysis (265 cases and 424 controls) and
      the transmission disequilibrium test (TDT) analysis (83 trios) for four
      polymorphisms (-G238A, -G308A, -C857T and -T1031C) in Japanese subjects. In a
      case-control analysis, there was no significant association between the promoter
      polymorphisms or haplotypes in the TNF-alpha gene and schizophrenia. In the TDT
      analysis, we also did not observe transmission distortion. Our results suggest
      that the above four polymorphisms in the promoter region of the TNF-alpha gene
      appear not to confer increased susceptibility for schizophrenia in a Japanese
      population.

PMID- 17559940
TI  - Spatial organization of direct hippocampal field CA1 axonal projections to the
      rest of the cerebral cortex.
AB  - The spatial distribution of axonal projections descending from rat field CA1 to
      thalamus and hypothalamus was analyzed previously with the PHAL method
      [Cenquizca, L.A., Swanson, L.W. 2006. An analysis of direct hippocampal cortical
      field CA1 axonal projections to diencephalon in the rat. J Comp Neurol 497:101
      114.]. The same experimental material was used here to define the topography of
      field CA1 association projections to other cerebral cortical areas. First, the
      results confirm and extend known intrahippocampal formation inputs to dentate
      gyrus, subiculum, presubiculum, parasubiculum, and entorhinal area, which are
      arranged generally along the formation's transverse axis and dominated by the
      subicular projection-by far the densest established by field CA1 anywhere in the
      brain. And second, field CA1 innervates a virtually complete ring of
      extrahippocampal formation cortex via three routes. A dorsal pathway from the
      dorsal third of field CA1 innervates moderately the retrosplenial area; a
      moderately strong ventral pathway from the ventral two thirds of field CA1
      passing through the longitudinal association bundle sends offshoots to visual,
      auditory, somatosensory, gustatory, main and accessory olfactory, and visceral
      areas-as well as the basolateral amygdalar complex and the agranular insular and
      orbital areas; and a cortical-subcortical-cortical pathway through the fornix
      from the whole longitudinal extent of field CA1 innervates rather strongly a
      rostral region that includes the tenia tecta along with the anterior cingulate,
      prelimbic, infralimbic, and orbital areas. The functional consequences of long
      term potentiation in field CA1 projection neurons remain to be explored.

PMID- 17559943
TI  - Immune parameters in mares resistant and susceptible to persistent post-breeding
      endometritis: effects of immunomodulation.
AB  - Our objective was to characterize immune parameters in susceptible (SM) and
      resistant (RM) mares, with and without artificial insemination (AI) and
      immunomodulation. Eight RM and eight SM were selected based on their reproductive
      history and functional tests. Both groups of mares were evaluated during three
      consecutive cycles: Cycle 1, untreated cycle (control); Cycle 2, AI with dead
      semen; Cycle 3, AI with dead semen and immunomodulation. Endometrial biopsies
      were taken during the three cycles as follows: Cycle 1--at estrus, when follicles
      > or =35mm and at diestrus (7+/-1 days after ovulation); Cycle 2--at estrus 24h
      post-AI, and at diestrus; Cycle 3--at estrus 24h after treatment with a
      Mycobacterium phlei cell-wall extract (MCWE) and AI, and at diestrus. The mRNA
      transcription (mRNAT) of IL-8 and IL-10 were determined by real-time PCR. Image
      analysis of immunohistochemistry slides was performed using digital software
      (Image-Pro Plus v 5.0; Media Cybernetics); the percentage of stained area was
      determined for Major Histocompatibility Complex II (MHC-II), polymorphonuclear
      leukocytes (PMN) and T lymphocytes (TL) on each tissue section. In Cycle 1, SM
      had significantly higher MHC-II, TL, PMN and IL-8 than RM during estrus (P<0.006,
      P<0.0005, P<0.05, respectively), while transcription of IL-10 was significantly
      lower than in RM (P<0.0001). During diestrus, SM had higher levels of TL, PMN and
      IL-8 than RM (P<0.0001). After AI (Cycle 2), SM had higher levels of IL-8 and
      lower levels of IL-10 than RM at estrus and no differences were detected for MHC
      II, TL and PMN positive cells. During diestrus in the same cycle, all the immune
      parameters were higher in SM mares (P<0.005, P<0.0004, P<0.0001, P<0.02,
      respectively). When MCWE was applied at the time of AI (Cycle 3), SM expressed
      significant higher levels of IL-10 24h after treatment (P<0.005), which were also
      higher than in the control Cycle 2 or after AI (Cycle 2). However, no significant
      differences were detected for MHC-II, lymphocytes-PMN or IL-8 between SM and RM
      during diestrus in Cycle 3. This study showed that SM had higher levels of all
      immune parameters except IL-10 than RM during Cycle 1. After AI (Cycle 2), the
      inflammatory condition persisted in SM but not RM mares until day 7 post
      ovulation. Following treatment with MCWE at the time of AI (Cycle 3) uterine
      immunological changes in SM resulted in an endometrial immune environment similar
      to that found in normal RM.

PMID- 17559944
TI  - Stable transduction of bovine TLR4 and bovine MD-2 into LPS-nonresponsive cells
      and soluble CD14 promote the ability to respond to LPS.
AB  - The interaction of bovine cells with lipopolysaccharide (LPS) was explored using
      human embryo kidney (HEK) 293 cell line stably transduced with bovine toll-like
      receptor-4 (TLR4) alone or in combination with bovine MD-2. These lines and mock
      transduced HEK293 cells were tested by flow cytometry for LPS-fluorescein
      isothiocyanate (LPS-FITC) binding, nuclear factor kappa B (NFkappaB) activation,
      interleukin-8 (IL-8) production and interferon-beta mRNA expression/interferon
      (IFN) type I production. Whereas bovine TLR4 was sufficient to promote binding of
      high concentrations of LPS-FITC, both bovine TLR4 and MD-2 were required for
      activation by LPS, as assessed by NFkappaB activation and IL-8 production.
      Induction of IFN bioactivity was not observed in doubly transduced HEK293 cells,
      and no evidence for IFN-beta mRNA induction in response to LPS was obtained,
      although cells responded by IFN-beta mRNA expression to stimulation by Sendai
      virus and poly-inosinic acid-poly-cytidylic acid (poly(I:C)). Cells stably
      transduced with both bovine TLR4 and bovine MD-2 responded to LPS by IL-8
      production, in decreasing order, in the presence of fetal bovine serum (FCS), of
      human serum, and of human serum albumin (HSA). The reduced activity in the
      presence of HSA could be restored by the addition of soluble CD14 (sCD14) but not
      of LPS binding protein (LBP). This is in contrast to macrophages which show a
      superior response to LPS in the presence of HSA when compared with macrophages
      stimulated by LPS in the presence of FCS. This suggests that macrophages but not
      HEK293 cells express factors rendering LPS stimulation serum-independent. Stably
      double-transduced cells reacted, in decreasing order, to LPS from Rhodobacter
      sphaeroides, to LPS from Escherichia coli, to synthetic lipd-IVa (compound 406),
      to diphosphoryl-lipid-A (S. minnesota) and to monophosphoryl-lipid-A (S.
      minnesota). They failed to react to the murine MD-2/TLR4 ligand taxol. This
      resembles the reactivity of bovine macrophages with regard to sensitivity
      (ED(50)) and order of potency but is distinct from the reactivity pattern of
      other species. This formally establishes that in order to react to LPS, cattle
      cells require serum factors (e.g. sCD14) and cell-expressed factors such as MD-2
      and TLR4. The cell lines described are the first of a series expressing defined
      pattern recognition receptors (PRR) of bovine origin. They will be useful in the
      study of the interaction of the bovine TLR4-MD-2 complex and Gram-negative bovine
      pathogens, e.g. the agents causing Gram-negative bovine mastitis.

PMID- 17559945
TI  - Vaccination experiments in the gadoid haddock, Melanogrammus aeglefinus L.,
      against the bacterial pathogen Vibrio anguillarum.
AB  - Vibrio anguillarum is one of the primary pathogens responsible for high levels of
      fish mortality in the aquaculture industry, and among gadoids O2a and b are the
      most common pathogenic serotypes. In this paper a variety of studies were
      performed to assess the optimal route by which to challenge haddock against this
      pathogen, and an optimal regime to vaccinate haddock. The most efficient method
      to challenge haddock with V. anguillarum in this study was immersion in a bath
      containing 10(7)cfu/ml, where 60% mortality was seen. Subsequent experiments
      showed that juvenile haddock could be protected against bacterial challenge with
      V. anguillarum, with a significant reduction in mortalities observed amongst the
      vaccination treatments when compared to the unvaccinated controls. However, as
      seen previously in cod studies, vaccination did not induce a specific antibody
      response.

PMID- 17559946
TI  - Identification and comparative analysis of Pax5 C-terminal isoforms expressed in
      human cord blood-derived B cell progenitors.
AB  - We identified three Pax5 isoforms due to alternative splicing of the C-terminal
      exons of its gene in cord blood (CB)-derived B cell progenitors cultivated on the
      murine bone marrow stromal (HESS-5) cells. Apart from wild type (wt), one isoform
      skips exon 9 without subsequent frameshift (del9), while the other has a
      frameshift insert between exons 8 and 9, resulting in novel C-terminal sequences
      (ins8'). Quantitative reverse transcription-polymerase chain reaction analysis
      revealed that wt mRNA could be detected in CB CD34(+) cells, but that del9 and
      ins8' isoforms only appeared after 1 or 3 weeks of co-culture, respectively.
      Expression of each isoform mRNA was markedly upregulated during B cell
      differentiation in vitro, and wild type continued to be the most abundant
      isoform. In a luciferase reporter assay using a synthetic CD19 enhancer, del9
      isoform revealed slightly lower activity and ins8' isoform showed much lower
      activity, compared with Pax5-wt. Furthermore, retroviral expression of each Pax5
      isoform in CB CD34(+) cells induced aberrant CD19 expression in a fraction of
      immature myeloid cells after 1 week of culture, although del9 and ins8' isoforms
      showed much less potent activity than Pax5-wt. These results suggest that Pax5-wt
      is quantitatively and qualitatively dominant over other C-terminal isoforms
      during human B cell differentiation.

PMID- 17559948
TI  - Regulatory T cells in cerebrospinal fluid from Behcet's disease with neurological
      manifestations.

PMID- 17559947
TI  - Lewis rats immunized with GM1 ganglioside do not develop peripheral neuropathy.
AB  - Elevated levels of anti-GM1 antibodies are associated with motor nerve syndromes.
      Although there is a lot of circumstantial evidence that anti-GM1 antibodies may
      be causing the disease, their precise role remains unclear. In order to study the
      role of anti-GM1 antibodies in the pathogenesis of peripheral neuropathy, eight
      Lewis rats were injected with GM1 ganglioside mixed with keyhole limpet
      hemocyanin (KLH) and emulsified with Freund's adjuvant and three rats were
      immunized with GM1 in liposomes. Although IgM class anti-GM1 antibodies were
      detected in all animals immunized with GM1, none of the animals exhibited overt
      signs of neuropathy during 6 months after initial immunization. IgG antibody to
      GM1 was not produced in any of the animals. There was no pathological evidence of
      nerve damage. These studies suggest that elevated levels of IgM anti-GM1
      antibodies by themselves do not cause nerve damage in rats.

PMID- 17559949
TI  - Evidence of an association between mannose binding lectin codon 54 polymorphism
      and adenoidectomy and/or tonsillectomy in children.
AB  - Mannose binding lectin (MBL) is a calcium-dependent lectin that plays an
      important role innate immunity by activating the complement pathway. There have
      been a number of studies describing an association between the MBL genotype and
      disease susceptibility. MBL deficiency has been described as one of the factors
      leading to a number of infections in children with recurrent upper respiratory
      tractus infections (URTI). We hypothesized that MBL deficiency may be associated
      with recurrent URTI, which requires adenoidectomy and/or adenotonsillectomy. In
      this study to clarify this hypothesis we investigated whether there may be an
      association between two low producing MBL variants and adenoidectomy and/or
      tonsillectomy due to recurrent URTI in children. Blood samples were collected,
      adenoidectomy and/or tonsillectomy due to recurrent URTI and 50 controls (mean
      age 80.53 +/- 32.62 months). In all patients and controls codon 54 and codon 57
      polymorphisms of the MBL gene were analyzed. None of the subjects from the
      patient group and control group carried codon 57 polymorphism of the MBL gene.
      The frequency of low-level MBL genotypes (AB and BB) for codon 54 polymorphism in
      the patient group was found to be significantly higher compared to the control
      subjects (55.7% versus 14%) (p<0.001). This study shows that the presence of low
      level MBL alleles is associated with adenoidectomy and/or tonsillectomy caused by
      recurrent URTI in children.

PMID- 17559950
TI  - Early acute otitis media: predictor for AOM and respiratory infections in
      schoolchildren?
AB  - OBJECTIVE: It has been reported that acute otitis media (AOM) and respiratory
      infectious morbidity still are common in schoolchildren. However, the
      significance of early initiation of AOM on later respiratory infections is not
      known. The aim of the study was to assess whether early initiation of AOM is a
      predictor for AOM and other respiratory infections in schoolchildren, and if
      environmental exposures and host factors in early life predict later AOM.
      METHODS: A population-based, prospective study of 3754 children born in Oslo in
      1992/93, of which 2549 children were followed from birth to 10 years. Main
      outcome measures were questionnaire-based information on AOM and other
      respiratory infections at ages 6 months, 1 year and 10 years. RESULTS: Of the 190
      (5.3%) children with one or more episodes of AOM before 6 months, 97 (51.1%)
      remained susceptible the next 6 months. The total number of children with one or
      more episodes of AOM from 6 to 12 months was 812 (25.1%). Of the 336 (13.2%) with
      AOM at 10, 95 (28.3%) also had AOM the first year of life. One or more episodes
      of tonsillopharyngitis or lower respiratory infections were experienced in 624
      (24.4%) of the children at 10 years. There was a predominance of boys with AOM
      the first year of life, while girls were more prone to AOM at age 10. AOM the
      first year of life was not strongly associated with AOM at age 10 with crude and
      adjusted odds ratios 1.3 (95% CI 1.0-1.6) and 1.2 (95% CI 0.9-1.5), respectively.
      A corresponding tendency was found for other respiratory infections
      (tonsillopharyngitis or lower respiratory infections) at age 10. Tobacco smoke
      exposure at birth, early life atopic eczema and otitis media surgery increased
      the risk of AOM at age 10. CONCLUSIONS: We found no strong association between
      early AOM and AOM and other respiratory infections in schoolchildren. Parental
      smoking at birth, early life atopic eczema and female gender were only weakly
      associated with AOM in 10-year olds while otitis media surgery was strongly
      associated with AOM in schoolchildren.

PMID- 17559951
TI  - Analysis of dynamic brain oscillations: methodological advances.
AB  - In recent years, new recording technologies have advanced such that, at high
      temporal and spatial resolutions, oscillations of neuronal networks can be
      identified from simultaneous, multisite recordings. However, because of the
      deluge of multichannel data generated by these experiments, achieving the full
      potential of parallel neuronal recordings also depends on the development of new
      mathematical methods that can extract meaningful information relating to time,
      frequency and space. Here, we aim to bridge this gap by focusing on up-to-date
      recording techniques for measurement of network oscillations and new analysis
      tools for their quantitative assessment. In particular, we emphasize how these
      methods can be applied, what property might be inferred from neuronal signals and
      potentially productive future directions. This review is part of the INMED and
      TINS special issue, Physiogenic and pathogenic oscillations: the beauty and the
      beast, derived from presentations at the annual INMED and TINS symposium
      (http://inmednet.com).

PMID- 17559953
TI  - The effects of chronic administration of established and putative antipsychotics
      on natural prepulse inhibition deficits in Brattleboro rats.
AB  - We previously reported that vasopressin deficient Brattleboro (BRAT) rats exhibit
      deficits in prepulse inhibition (PPI) of the startle reflex that are consistent
      with PPI deficits exhibited by patients with schizophrenia and other
      neuropsychiatric disorders. Preliminary evidence indicates that this may be the
      basis of a predictive model for antipsychotic drug efficacy. Here we report the
      effects of acute and chronic administration of established and putative
      antipsychotics on these PPI deficits. BRAT rats, compared to their derivative
      strain, Long Evans rats, exhibited significantly decreased PPI and startle
      habituation consistent with patients with schizophrenia and other
      neuropsychiatric disorders. The second generation antipsychotics, risperidone and
      clozapine as well as a neurotensin agonist (PD149163) increased BRAT rat PPI,
      whereas saline, the typical antipsychotic, haloperidol, and a vasopressin analog
      (1-desamino-D-arginine vasopressin) did not. Similar to their effects in humans,
      chronic administration of antipsychotic drugs produced stronger effects than
      acute administration. These results further support the BRAT rat as a model of
      sensorimotor gating deficits with predictive validity for antipsychotics. The
      model appears to be able to differentiate first generation from second generation
      antipsychotics, identify putative antipsychotics with novel mechanisms (i.e.,
      peptides) and reasonably model the therapeutic time course of antipsychotic drugs
      in humans.

PMID- 17559954
TI  - The complete mitochondrial DNA sequence of the monogenean Gyrodactylus thymalli
      (Platyhelminthes: Monogenea), a parasite of grayling (Thymallus thymallus).
AB  - We present the complete mitochondrial (mt) genome of Gyrodactylus thymalli, a
      monogenean ectoparasite on grayling (Thymallus thymallus). The circular genome is
      14788 bp in size and includes all 35 genes recognized from other flatworm mt
      genomes. The overall A+T content of the mt genome is 62.8%. Twenty regions of non
      coding DNA ranging from 1 to 111 bp in length were identified in addition to 2
      highly conserved large non-coding regions 799 bp and 767 bp in size. Compared to
      the recently described mt DNA of the closely related G. salaris from Atlantic
      salmon from Signaldalselva, Norway, the mitochondrial genome of G. thymalli from
      Hnilec, Slovakia, differs on average by 2.2%.

PMID- 17559955
TI  - Anemia and cardio-renal syndrome: a deadly association?
AB  - Despite growing recognition of the frequent presentation of cardio-renal
      syndrome, its underlying pathophysiology is not well understood, and no consensus
      as to its appropriate management has been achieved. On the other hand, there is
      growing evidence that the presence of anemia can worsen cardiac function and
      symtomps in patients with congestive heart failure (CHF) and that correction of
      anemia may beneficial. We believe that the treatment modalities, especially
      eryhtropoietin, to correct anemia will be an important part of our therapeutic
      armemanterium in the battle against CHF.

PMID- 17559956
TI  - Distribution and risk factors of bovine cysticercosis in Belgian dairy and mixed
      herds.
AB  - Bovine cysticercosis is an important food safety issue that is of economic
      concern. In Belgium, in the last years an increase in the number of cases, mostly
      light infections, was observed. The role of contact with contaminated surface
      water has been hypothesized as the main route of transmission. Based on abattoir
      records from 2001 till 2003 the distribution and risk factors of bovine
      cysticercosis among dairy and mixed farms were studied in four provinces, using
      Geographic Information Systems (GIS) and questionnaires. The risk factors were
      analysed using a case-control study design. The case group consisted of herds
      from which homebred cattle with cysticercosis had been detected at the abattoir;
      the control group was composed of herds where no cases had been detected. Case
      herds were distributed over the study area. A logistic regression analysis
      revealed that the location (province), the number of slaughtered cattle, the
      flooding of pastures, free access of cattle to surface water and the proximity of
      wastewater effluent were significant explanatory variables for bovine
      cysticercosis to be recorded in a herd.

PMID- 17559957
TI  - Fluorogenic surrogate substrates for toluene-degrading bacteria--are they useful
      for activity analysis?
AB  - Cultivated bacterial toluene degraders use one or several of four described
      pathways for the aerobic degradation of this priority groundwater contaminant. To
      be able to identify un-cultivated toluene-degrading bacteria within enriched or
      natural consortia, we attempted to develop a set of staining techniques that
      invariably label toluene-degrading bacteria while differentiating between the
      different degradation pathways. In the literature, we found suggestions for
      pathway-specific labels of individual cells that rely on the conversion of
      toluene surrogates into specific colored and fluorescent products. These
      surrogate substrates were phenylacetylene (PA), cinnamonitrile, 3
      hydroxyphenylacetylene (3-HPA), and indole. We were able to confirm that the
      chromogenic reactions reliably verified the pathway-specific reactions of well
      characterized toluene-degrading bacterial species. However, it was most
      surprising to find out that three (PA, 3-HPA and cinnamonitrile) of the four
      supplied surrogate substrates did not lead to any product fluorescence above the
      cultures' autofluorescence, neither inside of cells nor in supernatants. More
      disturbingly, the original surrogate compound 3-HPA was inherently fluorescent
      and found to stain cells at intensities that depended on their states in the cell
      cycle. Indoxyl originating from the surrogate substrate indole was the only
      fluorescent product that was formed. It was detected intracellularly when the
      cells were sealed with para-formaldehyde, but its appearance was unrelated to the
      presence of expressed toluene degradation pathways. These findings were
      scrutinized by fluorescence spectroscopy, fluorescence microscopy, and flow
      cytometry. Activity and growth of the test bacteria were determined by analyzing
      chromosome numbers and membrane integrity. Our results contradict literature
      reports that propose the surrogate fluorogenic substrates for the identification
      of toluene degraders and the identification of specific pathways used by them.

PMID- 17559958
TI  - Improvement of the conversion of polystyrene to polyhydroxyalkanoate through the
      manipulation of the microbial aspect of the process: a nitrogen feeding strategy
      for bacterial cells in a stirred tank reactor.
AB  - Pseudomonas putida CA-3 has been shown to accumulate the biodegradable plastic
      polyhydroxyalkanoate (PHA) when fed styrene or polystyrene pyrolysis oil as the
      sole carbon and energy source under nitrogen limiting growth conditions (67 mg
      nitrogen per litre at time 0). Batch fermentation of P. putida CA-3 grown on
      styrene or polystyrene pyrolysis oil in a stirred tank reactor yields PHA at 30%
      of the cell dry weight (CDW). The feeding of nitrogen at a rate of 1mg N/l/h
      resulted in a 1.1-fold increase in the percentage of CDW accumulated as PHA. An
      increase in the rate of nitrogen feeding up to 1.5mg N/l/h resulted in further
      increases in the percentage of the cell dry weight composed of PHA. However,
      feeding rates of 1.75 and 2mg N/l/h resulted in dramatic decreases in the
      percentage of cell dry weight composed of PHA. Interestingly nitrogen was not
      detectable in the growth medium after 16 h, in any of the growth conditions
      tested. A higher cell density was observed in cells supplied with nitrogen and
      thus further increases in the overall production of PHA were observed through
      nitrogen feeding. The highest yield of PHA was 0.28 g PHA per g styrene supplied
      with a nitrogen feeding rate of 1.5mg/l/h.

PMID- 17559959
TI  - Establishment of a GDP-mannose 4,6-dehydratase (GMD) knockout host cell line: a
      new strategy for generating completely non-fucosylated recombinant therapeutics.
AB  - Currently, removal of core fucose from the Fc oligosaccharides of therapeutic
      antibodies is widely recognized as being of great importance for the effector
      function of antibody-dependent cellular cytotoxicity, and alpha-1,6
      fucosyltransferase (FUT8) knockout cells have been generated as an ideal host
      cell line for manufacturing such therapeutics. Here, we attempted to identify
      genes other than FUT8 that could be targeted for the manufacture of non
      fucosylated therapeutics. Loss-of-function analyses using siRNAs against three
      key genes involved in oligosaccharide fucosylation in Chinese hamster ovary (CHO)
      cells revealed that there was a positive correlation between the Fc
      oligosaccharide fucosylation and the mRNA expression through the origin in the
      cases of both GDP-fucose 4,6-dehydratase (GMD) and FUT8, but not for the GDP
      fucose transporter, suggesting that there is no functional redundancy in GMD and
      FUT8. GMD knockout CHO/DG44 cells were successfully established, and were
      confirmed to be devoid of intracellular GDP-fucose and to produce completely non
      fucosylated antibodies. GMD knockout cells recovered their fucosylation
      capability through the salvage pathway upon addition of l-fucose into the culture
      medium, and exhibited equable morphology, growth kinetics and recombinant protein
      productivity, demonstrating that loss of oligosaccharide fucosylation has no
      impact on these cellular phenotypes. Our results demonstrate that GMD knockout is
      a new strategy applicable to the manufacture of non-fucosylated therapeutic
      antibodies, and completely O-fucose-negative therapeutics as well.

PMID- 17559960
TI  - Optimisation of aqueous two-phase extraction of human antibodies.
AB  - The purification of human antibodies in an aqueous two-phase system (ATPS)
      composed of polyethylene glycol (PEG) 6000 and phosphate was optimised by surface
      response methodology. A central composite design was used to evaluate the
      influence of phosphate, PEG and NaCl concentration and of the pH on the purity
      and extraction yield of IgG from a simulated serum medium. The conditions that
      maximise the partition of IgG into the upper phase were determined to be high
      concentrations of NaCl and PEG, low concentrations of phosphate and low pH
      values. An ATPS composed of 12% PEG, 10% phosphate, 15% NaCl at pH 6 was further
      used to purify human monoclonal antibodies from a Chinese Hamster Ovary (CHO)
      concentrated cell culture supernatant with a recovery yield of 88% in the upper
      PEG-rich phase and a purification factor of 4.3. This ATPS was also successfully
      used to purify antibodies from a hybridoma cell culture supernatant with a
      recovery yield of 90% and a purification factor of 4.1.

PMID- 17559961
TI  - Process Analytical Technology (PAT): batch-to-batch reproducibility of
      fermentation processes by robust process operational design and control.
AB  - The Process Analytical Technology (PAT) initiative of the FDA is a reaction on
      the increasing discrepancy between current possibilities in process supervision
      and control of pharmaceutical production processes and its current application in
      industrial manufacturing processes. With rigid approval practices based on
      standard operational procedures, adaptations of production reactors towards the
      state of the art were more or less inhibited for long years. Now PAT paves the
      way for continuous process and product improvements through improved process
      supervision based on knowledge-based data analysis, "Quality-by-Design"-concepts,
      and, finally, through feedback control. Examples of up-to-date implementations of
      this concept are presented. They are taken from one key group of processes in
      recombinant pharmaceutical protein manufacturing, the cultivations of genetically
      modified Escherichia coli bacteria.

PMID- 17559963
TI  - Pulmonary rehabilitation in chronic obstructive pulmonary disease.
AB  - Pulmonary rehabilitation, a multidisciplinary and structured intervention for
      patients with chronic pulmonary diseases, has been shown to improve exercise
      tolerance, reduce dyspnea and improve health-related quality of life. Pulmonary
      rehabilitation appears to be cost-effective, since it reduces health care
      utilization. Exercise training represents the cornerstone of every pulmonary
      rehabilitation program. To obtain clinically relevant effects, training should
      closely supervised, of high intensity, lasting 30-45 min for at least 3
      days/week. Patients should undertake a minimum of 20 sessions, but longer
      programs result in larger and more long-lasting effects. Education and self
      management programs have been shown to result in a substantial reduction in
      hospital admissions. Nutritional intervention should be considered for patients
      who are underweight or those with body composition abnormalities. Patients
      reporting fear and anxiety may benefit from psychosocial support, and the
      integration of occupational therapy in a pulmonary rehabilitation program can
      improve independence in activity. Multidisciplinary pulmonary rehabilitation is
      preferably implemented in an outpatient hospital- or community-based setting.
      Inpatient programs are suited for patients with limited transportation
      capabilities or severe deconditioning. The most convincing effects of home-based
      rehabilitation are in maintaining the improvements obtained in an outpatient
      setting.

PMID- 17559964
TI  - The GNB3 C825T polymorphism affects response to HCV therapy with pegylated
      interferon in HCV/HIV co-infected but not in HCV mono-infected patients.
AB  - BACKGROUND/AIMS: Response to HCV treatment with pegylated interferon-alpha is
      variable but might at least in part depend on genetic host factors. The G protein
      beta3 unit (GNB3) C825T polymorphism has been shown to affect treatment response
      in HCV mono-infection. Here, we analyzed the impact of the GNB3 genotype in the
      context of HCV/HIV co-infection. METHODS: HIV/HCV co-infected (n=112) and HCV
      mono-infected patients (n=150), receiving therapy with pegylated IFN
      alpha/ribavirin, were enrolled into this study. Furthermore, we analyzed 220
      healthy and 92 HIV mono-infected patients. GNB3 genotype was defined and
      correlated with respect to treatment response. RESULTS: GNB3 genotype
      distribution differed significantly between HIV/HCV co-infected patients and HIV
      positive/HCV-negative (p=0.0002) or healthy controls (p=0.03). Patients with a
      GNB3 CC genotype had significantly lower SVR rates as compared to carriers of a
      non-CC genotype (52% versus 77%; p=0.018). In a logistic regression analysis the
      GNB3 genotype and the HCV genotype were significantly associated with response to
      treatment (p=0.018). In contrast to HIV/HCV co-infected patients, GNB3 genotype
      did not affect response to treatment in HCV mono-infected patients. CONCLUSIONS:
      The GNB3 825 CC genotype is associated with poor SVR rates in HIV/HCV co-infected
      patients. This underlines the impact of genetic host factors for treatment
      response.

PMID- 17559965
TI  - Epigenetics and aging: the targets and the marks.
AB  - 'Aging epigenetics' is an emerging field that promises exciting revelations in
      the near future. Here we focus on the functional and biological significance of
      the epigenetic alterations that accumulate during aging and are important in
      tumorigenesis. Paradigmatic examples are provided by the global loss of DNA
      methylation in aging and cancer and by the promoter hypermethylation of genes
      with a dual role in tumor suppression and progeria, such as the Werner syndrome
      (WRN) and lamin A/C genes. Another twist is provided by sirtuins, a family of NAD
      dependent deacetylases that act on Lys16 of histone H4, which are emerging as a
      link between cellular transformation and lifespan.

PMID- 17559966
TI  - Mouse duplicate genes are as essential as singletons.
AB  - Duplicate genes in mouse are widely thought to have functional redundancy, and to
      be less essential than singleton genes. We analyzed nearly 3900 individually
      knocked out mouse genes and discovered that the proportion of essential genes is
      approximately 55% in both singletons and duplicates. This suggests that mammalian
      duplicates rarely compensate for each other, and that the absence of phenotypes
      in mice deficient for a duplicate gene should not be automatically attributed to
      paralogous compensation.

PMID- 17559967
TI  - Predictive modelling of dispersion controlled reactive plumes at the laboratory
      scale.
AB  - A model-based interpretation of laboratory-scale experimental data is presented.
      Hydrolysis experiments carried out using thin glass tanks filled with glass beads
      to construct a hypothetical and inert, homogeneous porous medium were analysed
      using a 2D numerical model. A new empirical formula, based upon results for non
      reactive (tracer) experiments is used to calculate transversal dispersivity
      values for a range of grain sizes and any flow velocities. Combined with
      effective diffusion coefficients calculated from Stokes-Einstein type equations,
      plume lengths arising from mixing between two solutes can be predicted accurately
      using numerical modelling techniques. Moreover, pH and ion concentration profiles
      lateral to the direction of flow of the mixing species can be determined at any
      given point downstream, without the need for result fitting. In our case, this
      approach does not lead to overpredictions of lateral mixing, as previously
      reported when using parameters derived from non-reactive tracer experiments to
      describe reactive solute transport. The theory is based on the assumption of
      medium homogeneity.

PMID- 17559968
TI  - ARF6 in the nervous system.
AB  - Actin cytoskeleton dynamics and membrane trafficking are tightly connected and
      are among the most important driving forces of neuronal development, basic
      synaptic transmission events, and synaptic plasticity. One group of proteins
      involved in coordination of these two processes is the family of ADP ribosylation
      factors (ARFs) regulating actin dynamics, lipid modification and membrane
      trafficking. ARF6 is the only member of the ARF family that can simultaneously
      regulate actin cytoskeleton changes and membrane exchange between plasma membrane
      and endocytic compartments. The presence of ARF6 and its guanine nucleotide
      exchange factors (GEFs) and GTPase-activating proteins (GAPs) in the brain, as
      well as its capability to regulate several aspects of neuronal development and
      synaptic plasticity, has been recently demonstrated. The main purpose of this
      review is to present the current knowledge about how ARF6 can influence
      morphological processes crucial for proper formation of the neuronal circuits in
      the brain, including dendrite and axon differentiation, development of dendritic
      arbor complexity and dendritic spine formation. Potential effects of ARF6 on
      synaptic events resulting from its ability to control exo- and endocytosis will
      be also discussed.

PMID- 17559969
TI  - Shifting toward balance: measuring the distribution of workload among emergency
      physician teams.
AB  - STUDY OBJECTIVE: The objective of this investigation is to determine time
      dependent workload patterns for emergency department (ED) physician teams across
      work shifts. A secondary aim was to demonstrate how ED demand patterns and the
      timing of shift changes influence the balance of workload among a physician team.
      METHODS: Operational measurements of an adult ED were collected from a clinical
      information system to characterize physician workload patterns during all current
      work shifts. Plots of patient load versus time were developed for each physician
      shift, in which patient load was defined as the number of patients a physician
      simultaneously managed at a point in time. Patient-load curves for each shift
      were superimposed during 24 hours to display how patient load was distributed
      among a team of physicians. RESULTS: Resident shift changes during daily peak
      occupancy periods caused patient load imbalances so that residents on a
      particular shift consistently managed a disproportionate number of patients (mean
      9.4 patients; 95% confidence interval [CI] 6.7 to 12.1 patients) compared with
      other residents on duty (mean 3.4 patients; 95% CI 2.1 to 4.7 patients).
      CONCLUSION: Physician patient load patterns and ED demand patterns should be
      taken into consideration when physician shift times are scheduled so that patient
      load may be balanced among a team. Real-time monitoring of physician patient load
      may reduce stress and prevent physicians from exceeding their safe capacity for
      workload.

PMID- 17559971
TI  - Perceptual reasons for resistance to change in the emergency department use of
      holding chambers for children with asthma.
AB  - STUDY OBJECTIVE: We explore perceptions surrounding use of portable inhalers and
      holding chambers (spacers) for delivery of beta-agonist respiratory medications
      to children in the emergency department (ED) and factors influencing practice
      change. METHODS: This was a qualitative study guided by principles of grounded
      theory. Data were collected through focus groups and individual interviews at 2
      sites in eastern Canada: Hospital A, where inhalers and holding chambers are used
      routinely; and Hospital B, where prevailing practice is the use of nebulization.
      Participant encounters were transcribed verbatim and analyzed for emerging
      themes. RESULTS: At Hospital A, 6 physicians and 7 nurses participated in
      separate focus groups. Four interviews were conducted with physician, nurse,
      respiratory therapy, and pharmacy leaders. At Hospital B, 4 physicians and 3
      nurses participated in focus groups, and 6 leaders were interviewed. Perceptions
      negatively influencing the adoption of inhalers and holding chambers included
      increased workload, increased equipment costs, myths about the superiority of
      nebulization, and interprofessional conflict. Health professionals reported that
      their most prominent concern about administering medications with inhalers and
      holding chambers was the time demand. Nurses especially seemed to think this way,
      tipping the balance in favor of nebulization despite knowledge of evidence to the
      contrary and affecting physician decisionmaking as well. Professional
      territorialism appeared to hinder efforts to ameliorate workload issues through
      the use of respiratory therapists in the ED. CONCLUSION: Findings from this study
      could be used to inform a change program to close the gap between evidence and
      practice with respect to use of inhalers and holding chambers in the ED.

PMID- 17559970
TI  - Comparative treatment of alpha-amanitin poisoning with N-acetylcysteine,
      benzylpenicillin, cimetidine, thioctic acid, and silybin in a murine model.
AB  - STUDY OBJECTIVE: The foraging of wild mushrooms can be complicated by toxicity
      from several mushroom types. Amatoxin, a peptide contained in several mushroom
      species, accounts for the majority of severe mushroom poisonings by binding to
      RNA polymerase II irreversibly, leading to severe hepatonecrosis. There is no
      effective antidote for severe amatoxin poisoning. We compare the effectiveness of
      5 potential antidotal therapies in limiting the degree of hepatonecrosis in a
      randomized, controlled, murine model of amatoxin-induced hepatotoxicity. METHODS:
      One hundred eighty male Institute of Cancer Research mice were randomized into 6
      equal groups. Within each group, 21 mice were intraperitoneally injected with 0.6
      mg/kg of alpha-amanitin (amatoxin); the remaining 9 were injected with 0.9%
      normal saline solution. Four hours postinjection, each group of 30 mice was
      randomized to 1 of 5 intraperitoneal treatments (N-acetylcysteine,
      benzylpenicillin, cimetidine, thioctic acid, or silybin) or normal saline
      solution. Repeated dosing was administered intraperitoneally every 4 to 6 hours
      for 48 hours. After 48 hours of treatment, each subject was killed, cardiac blood
      was aspirated for hepatic aminotransferase measurements (alanine transaminase and
      aspartate transaminase), and liver specimens were harvested to evaluate the
      extent of hepatonecrosis. The degree of hepatonecrosis was determined by a
      pathologist blinded to the treatment group and divided into 5 categories
      according to percentage of hepatonecrosis. RESULTS: Amanitin significantly
      increased aspartate transaminase in treated mice compared with normal saline
      solution-treated controls (mean [SD] 2,441 [2,818] IU/L versus 310 [252]; P=.03).
      None of the antidotal therapies were found to significantly decrease the increase
      in aminotransferases compared with controls. Further, none of the antidotal
      therapies demonstrated an important decrease in hepatonecrosis compared with
      controls when a histologic grading scale was used. CONCLUSION: In this murine
      model, N-acetylcysteine, benzylpenicillin, cimetidine, thioctic acid, and silybin
      were not effective in limiting hepatic injury after alpha-amanitin poisoning.
      Increases of aminotransferases and degrees of histologic hepatonecrosis were not
      attenuated by these antidotal therapies.

PMID- 17559972
TI  - Low diagnostic yield of electrocardiogram testing in younger patients with
      syncope.
AB  - STUDY OBJECTIVE: Routine ECG testing is recommended in the evaluation of syncope,
      although the value of such testing in young patients is unclear. For ECG testing,
      we assess the diagnostic yield (frequency that ECG identified the reason for
      syncope) and predictive accuracy for 14-day cardiac events after an episode of
      syncope as a function of age. METHODS: Adult patients with syncope or near
      syncope were prospectively enrolled for 1 year at a single academic emergency
      department (ED). A 3-physician panel reviewed ED charts, hospital records, and
      telephone interview forms to identify predefined cardiac events. The primary
      outcome included all 14-day, predefined cardiac events including arrhythmia,
      myocardial ischemia, and structural heart disease. RESULTS: Of 592 eligible
      patients, 477 (81%) provided informed consent. Direct telephone contact or
      admission/outpatient records were successfully obtained for 461 (97%) patients,
      who comprised the analytic cohort. There were 44 (10%) patients who experienced a
      14-day cardiac event. Overall diagnostic yield of ECG testing was 4% (95%
      confidence interval 2% to 6%). For patients younger than 40 years, ECG testing
      had a diagnostic yield of 0% (95% confidence interval 0% to 3%) and was
      associated with a 10% frequency of abnormal findings. CONCLUSION: ECG testing in
      patients younger than 40 years did not reveal a cardiac cause of syncope and was
      associated with a significant frequency of abnormal ECG findings unrelated to
      syncope. Although our findings should be verified in larger studies, it may be
      reasonable to defer ECG testing in younger patients who have a presentation
      consistent with a benign cause of syncope.

PMID- 17559973
TI  - Emergency department communication links and patterns.
AB  - STUDY OBJECTIVE: We characterize and describe the communication links and
      patterns between and within emergency department (ED) practitioner types.
      METHODS: This is a prospective, observational study of emergency physician and
      nursing staff communication patterns in an academic ED using link analysis
      techniques. Twenty ED staff members were observed in the pediatric and adult
      acute areas of the ED, including attending physicians, residents, nurses, and
      charge nurses. Data were recorded for each communication event, including
      duration, mode, partner, location, and interruptions. Because this study was
      intended to focus on professionally related communication between staff, social
      interactions and direct patient interactions were excluded. Frequency percentage
      and duration were calculated for each measure, and link analysis graphs were
      prepared to assist in interpretation of the data. RESULTS: One thousand six
      hundred sixty-five total communication events were recorded during a total of 39
      hours 12 minutes of observation. Face-to-face communication was the most common
      mode. Communication links and patterns were described and graphically represented
      using a link analysis technique. Communication gaps were found between ambulance
      providers and the providers who would ultimately take care of the patient during
      their ED stay. Attending physicians communicated often despite caring for
      separate patients, and the charge nurse seemed to be the hub for communication,
      linking ED personnel with non-ED staff. In the adult area, interruption rates
      ranged from 6.9 per hour (attending physician) to 0.5 per hour (bedside nurse),
      and in the pediatric area they ranged from 3.6 per hour (attending physician) to
      0.3 (bedside nurse). CONCLUSION: Distinct patterns are identified. These results
      will be helpful in designing future communication adjuncts in the ED.

PMID- 17559974
TI  - Role of VIP and PACAP in islet function.
AB  - Vasoactive intestinal polypeptide (VIP) and pituitary adenylate cyclase
      activating polypeptide (PACAP) are two closely related neuropeptides that are
      expressed in islets and in islet parasympathetic nerves. Both peptides bind to
      their common G-protein-coupled receptors, VPAC1 and VPAC2, and PACAP, in addition
      to the specific receptor PAC1, all three of which are expressed in islets. VIP
      and PACAP stimulate insulin secretion in a glucose-dependent manner and they both
      also stimulate glucagon secretion. This action is achieved through increased
      formation of cAMP after activation of adenylate cyclase and stimulation of
      extracellular calcium uptake. Deletion of PAC1 receptors or VPAC2 receptors
      results in glucose intolerance. These peptides may be of importance in mediating
      prandial insulin secretion and the glucagon response to hypoglycemia. Animal
      studies have also suggested that activation of the receptors, in particular VPAC2
      receptors, may be used as a therapeutic approach for the treatment of type 2
      diabetes. This review summarizes the current knowledge of the potential role of
      VIP and PACAP in islet function.

PMID- 17559975
TI  - Acoustic overstimulation facilitates the expression of glutamate-cysteine ligase
      catalytic subunit probably through enhanced DNA binding of activator protein-1
      and/or NF-kappaB in the murine cochlea.
AB  - Glutamate-cysteine ligase (GCL), previously known as gamma-glutamylcysteine
      synthetase, is the rate-limiting enzyme for GSH synthesis. The expression of GCL
      is mediated by activator protein-1 (AP-1) and nuclear factor-kappa B (NF-kappaB),
      which are known to participate in stress-induced apoptotic pathways in neuronal
      cells. In this study, we investigated the changes in the level of these
      transcription factors as well as of GCL catalytic subunit in the cochlea in
      response to acoustic overstimulation. Nuclear extracts were prepared from the
      cochlear at various time points after intense noise exposure (4kHz octave band,
      125dB sound pressure level, 5h), and then determined DNA binding activity of the
      transcription factors. AP-1 DNA binding was markedly increased 2-12h after the
      noise exposure, with a peak at 2h after the exposure. NF-kappaB DNA binding was
      also increased immediately after the exposure. Semi-quantitative RT-PCR revealed
      that the catalytic subunit of GCL mRNA was elevated in the cochlea 2-24h post the
      exposure. Further immunohistochemical study revealed that increased level of GCL
      catalytic subunit observed at least in the spiral ganglion cells after the
      exposure. These results suggest that intense noise exposure facilitates the
      expression of GCL catalytic subunit in the cochlea possibly through the
      activation of transcription factors including AP-1 and NF-kappaB.

PMID- 17559976
TI  - S1P-receptors in PC12 and transfected HEK293 cells: molecular targets of
      hypotensive imidazoline I(1) receptor ligands.
AB  - The present study aimed at elucidating the molecular identity of the proposed
      "I(1)-imidazoline receptors", i.e. non-adrenoceptor recognition sites via which
      the centrally acting imidazolines clonidine and moxonidine mediate a major part
      of their effects. In radioligand binding experiments with [(3)H]clonidine and
      [(3)H]lysophosphatidic acid on intact, alpha(2)-adrenoceptor-deficient PC12
      cells, moxonidine, clonidine, lysophosphatidic acid and sphingosine-1-phosphate
      (S1P) competed for the specific binding sites of both radioligands with similar
      affinities. RNA interference with the rat S1P(1)-, S1P(2)- or S1P(3)-receptor
      abolished specific [(3)H]lysophosphatidic acid binding. [(3)H]Clonidine binding
      was markedly decreased by siRNA targeting S1P(1)- and S1P(3)-receptors but not by
      siRNA against S1P(2)-receptors. Finally, in HEK293 cells transiently expressing
      human S1P(3)-receptors, sphingosine-1-phosphate, clonidine and moxonidine induced
      increases in intracellular calcium concentration, moxonidine being more potent
      than clonidine; this is in agreement with the known properties of the "I(1)
      imidazoline receptors". The present results indicate that the "I(1)-imidazoline
      receptors" mediating effects of clonidine and moxonidine in PC12 and the
      transfected HEK293 cells belong to the S1P-receptor family; in particular, the
      data obtained in PC12 cells suggest that the I(1) imidazoline receptors represent
      a mixture of S1P(1)- and S1P(3)-receptors and/or hetero-dimers of both.

PMID- 17559977
TI  - Activator protein-1 responsive to the group II metabotropic glutamate receptor
      subtype in association with intracellular calcium in cultured rat cortical
      neurons.
AB  - Activation of ionotropic glutamate (Glu) receptors, such as N-methyl-d-aspartate
      receptors, is shown to modulate the gene transcription mediated by the
      transcription factor activator protein-1 (AP1) composed of Fos and Jun family
      proteins in the brain, while little attention has been paid to the modulation of
      AP1 expression by metabotropic Glu receptors (mGluRs). In cultured rat cortical
      neurons, where constitutive expression was seen with all groups I, II and III
      mGluR subtypes, a significant and selective increase was seen in the DNA binding
      activity of AP1 120 min after the brief exposure to the group II mGluR agonist
      (2S,2'R,3'R)-2-(2',3'-dicarboxycyclopropyl)glycine (DCG-IV) for 5 min. In
      cultured rat cortical astrocytes, by contrast, a significant increase was induced
      by a group I mGluR agonist, but not by either a group II or III mGluR agonist.
      The increase by DCG-IV was significantly prevented by a group II mGluR antagonist
      as well as by either an intracellular Ca(2+) chelator or a voltage-sensitive
      Ca(2+) channel blocker, but not by an intracellular Ca(2+) store inhibitor.
      Moreover, DCG-IV significantly prevented the increase of cAMP formation by
      forskolin in cultured neurons. Western blot analysis revealed differential
      expression profiles of Fos family members in neurons briefly exposed to DCG-IV
      and NMDA. Prior or simultaneous exposure to DCG-IV led to significant protection
      against neuronal cell death by NMDA. These results suggest that activation of the
      group II mGluR subtype would modulate the gene expression mediated by AP1 through
      increased intracellular Ca(2+) levels in cultured rat cortical neurons.

PMID- 17559978
TI  - Relevance of molecular weight of chitosan-N-2-hydroxypropyl trimethyl ammonium
      chloride and their antioxidant activities.
AB  - The antioxidant potency of high/low molecular weight quaternary chitosan
      derivatives was investigated employing various established systems in vitro, such
      as superoxide (O*(2)(-)) and hydroxyl (*OH) radicals scavenging, reducing power
      and iron ion chelating. As expected, we obtained several satisfying results, as
      follow: firstly, low molecular weight quaternary chitosan had stronger scavenging
      effect on O*(2)(-) and *OH than high molecular weight quaternary chitosan.
      Secondly, the reducing power of low molecular weight quaternary chitosan was more
      pronounced than that of high molecular weight quaternary chitosan. Thirdly,
      ferrous ion chelating potency were showed to increase first and decrease
      afterwards with increasing concentration for two kinds of quaternary chitosans,
      namely, they have not concentration-dependence. However, the scavenging rate and
      reducing power of high and low molecular weight quaternary chitosans increased
      with their increasing concentrations, and hence were concentration-dependent.

PMID- 17559979
TI  - [Genetic abnormalities in multiple myeloma: role in oncogenesis and impact on
      survival].
AB  - PURPOSE: Recent development of interphase fluorescence in situ hybridization
      (FISH) allows analysis on non-proliferant plasma cells. We describe the most
      frequent genetic abnormalities in multiple myeloma and their prognostic value.
      CURRENT KNOWLEDGE AND KEY POINTS: Most frequent genetic abnormalities are
      illegitimate rearrangements involving the IGH gene at 14q32 (60% of patients),
      hyperdiploidy (50 to 60% of patients), chromosome 13 deletion (40 to -50% of
      patients), chromosome 1q gain (30 to -40% of patients) chromosome 17 deletion
      (10% of patients). Some of these genetics abnormalities are observed in
      monoclonal gammopathy of undetermined significance (MGUS), a pre-malignant state.
      t(4;14) and t(14;16) translocations and chromosome 17 deletion negatively impact
      the overall survival. Patients with these genomic aberrations should be treated
      with specific treatment. FUTURE PROSPECTS AND PROJECTS: Identification of genetic
      abnormalities is important for evaluation of prognosis and treatment protocol in
      multiple myeloma.

PMID- 17559980
TI  - [Diagnosis of anemia in alcoholic cirrhosis].
AB  - PURPOSE: Anemia in patients with alcoholic liver cirrhosis is a common issue. The
      diagnosis could be difficult because of the multiplicity of causes, usually
      associated, and specificities in the diagnostic approach. This subject has not
      been reviewed for almost two decades. We propose a review based upon analysis of
      the literature and our clinical experience. CURRENT KNOWLEDGE AND KEY POINTS:
      Because of the alcoholism and the biological consequences of the liver disease,
      laboratory findings, especially the mean corpuscular volume, should be
      interpreted with caution in the diagnostic approach. Despite these drawbacks, the
      diagnosis of anemia is detailed according to the usual plan: normocytic,
      macrocytic and microcytic anemias. Finally, we propose practical guidelines.
      FUTURE PROSPECTS AND PROJECTS: Further prospective studies should assess the real
      burden of nutritional deficiencies, easily treatable. The prognostic significance
      of hemolytic anemias in patients with alcoholic liver cirrhosis should be
      studied.

PMID- 17559981
TI  - [Behcet disease and hemoptysis].

PMID- 17559982
TI  - [New treatment of multiple myeloma].
AB  - PURPOSE: After decades of minimal progress, two new classes of drugs with novels
      mechanisms of action: immunomodulatory drugs (thalidomide and lenalidomide) and
      proteasome inhibitors (bortezomib) have shown great activity for the treatment of
      multiple myeloma. CURRENT KNOWLEDGE AND KEY POINTS: Thalidomide acts by a variety
      of mechanisms; its efficacy is well known in disease relapse especially
      associated with dexamethasone. Recent results prove that combination of
      thalidomide with melphalan and prednisone should be considered as the first line
      standard of care in elderly patient. The main side effects are peripheral
      neuropathy and deep-vein thrombosis. Bortezomib is the first proteasome
      inhibitor. It is approved for the treatment in first disease relapse. The
      combination with glucocorticoids is synergistic. This combination in induction
      treatment before autologous stem cell transplantation is promising, as well as
      the combination with melphalan and prednisone in elderly patient. The main
      toxicities are fatigue and peripheral neuropathy. Lenalidomide is a structural
      analogue of thalidomide. Its efficacy in combination with dexamethasone has been
      proved in relapsing patients. The main toxicity is hematologic. Utilisation as
      first line treatment is also promising. FUTURE PROSPECTS AND PROJECTS: These
      three drugs have toxicities predictable and manageable and can be used
      successively or in combination for greater effectiveness. They have an impact on
      the multiple myeloma treatment strategies and on the disease course itself.

PMID- 17559983
TI  - [Dermatomyositis associated with hepatosplenic gamma delta T-cell lymphoma].
AB  - INTRODUCTION: Peripheral T cell lymphomas are a heterogeneous group of post
      thymic, mature lymphoid malignancies, accounting for approximately 10-15% of all
      non-Hodgkin's lymphomas. A rare entity within this group is represented by
      hepatosplenic T cell lymphoma, characterized by primary extranodal disease with
      infiltration of the liver and the spleen and by expression of the T cell receptor
      gamma delta chain. EXEGESIS: A 64-year old man with dermatomyositis developed
      rapid-onset paraparesia and deafness. Cerebrospinal fluid analysis revealed large
      granular lymphomatous cells with CD3+ CD4- CD8- CD7+ CD16- CD56- surface
      antigens, expressing the gamma delta T-cell receptor. There was no evidence of
      skin or bone marrow infiltration by lymphoma or any other involvement. This is
      the first report of dermatomyositis associated with a gamma delta T-cell lymphoma
      (GDTL). Moreover, primitive and isolated meningeal involvement of such lymphomas
      has never been described before. CONCLUSION: GDTL should be added to the
      differential list of neoplasia associated with dermatomyositis.
      Physiopathological mechanisms implicated in the neurological involvement of such
      lymphomas need to be elucidated.

PMID- 17559984
TI  - [Subcutaneous nodules].

PMID- 17559985
TI  - Cultural sensitivity training: description and evaluation of a workshop.
AB  - We describe the materials used to develop cultural sensitivity within 350 nursing
      students. These involved a lecture on dimensions of difference between east and
      west, exercises on names and early memories and the construction of a cultural
      genogram. In addition, we report the results of an evaluation study which was
      both quantitative and qualitative. The questionnaire data indicated that the
      workshop was useful and clear. Using IPA analysis, the interview data indicated
      seven major themes: a close, safe space in which to talk, increased cultural
      awareness, freedom to inquire, awareness that cultural self-knowledge is
      essential for developing cultural sensitivity, impact of cultural sensitivity
      training on professional work with people, limitations and suggestions for future
      workshops and wanting more workshops in a similar vein. Second stage IPA analysis
      indicated four levels of cultural sensitivity: 'Them', 'Us and Them', 'We' and
      'Transcendent'. Integrating the findings of both the qualitative and the
      qualitative data, we conclude that the workshop was highly appreciated and that
      there is a demand for more training in this area. Implications for further
      training in cultural sensitivity are considered.

PMID- 17559986
TI  - A comparative, longitudinal study of stress in student nurses in five countries:
      Albania, Brunei, the Czech Republic, Malta and Wales.
AB  - BACKGROUND AND AIMS: Stress amongst nursing students is a global issue. There is
      an absence of published international comparative studies which investigate this
      and so this paper sets out to explore the sources of stress among nursing
      students throughout their course of study and to determine whether they were more
      stressed by academic or clinical factors across five different countries
      (Albania, Brunei, the Czech Republic, Malta and Wales). Although each country,
      within this study, has a unique culture, a cross-cultural comparison can be made
      in an attempt to better understand stress in the student nursing population.
      METHODS: The study was undertaking using a descriptive quantitative design using
      the Stress in Nurse Education Questionnaire with 1707 nursing students across the
      five countries. RESULTS: The mean score for the total sample for all the items on
      the stress scale was 52.3 (SD 17.1). The sample from Wales had the lowest mean
      score and those in Brunei had the highest. Students in Brunei and Malta were more
      stressed by the academic elements of the course than by the clinical elements.
      Whereas for those students in the Czech Republic For students in Wales and in
      Albania - Korce there were no differences in stress experienced between the
      academic and clinical elements of the course. The results indicated that there
      were no significant differences in total stress scores by year of study for
      students in Albania - Tirana, Albania-Korce, Malta and Wales. In Brunei however,
      ANOVA revealed that there were significant differences in total stress scores by
      year of study. Further analysis revealed that students in year 3 scored higher on
      the overall scale than students in year 1. The individual item on the stress
      scale with highest mean in the Albania - Korce and the Albania-Tirana sample was
      "The death of a patient" whilst the Bruneian sample, Maltese sample and Welsh
      sample opted for "Revising for and sitting examinations" and the Czech sample
      chose: "Continuous pressure to meet deadlines for assessments". CONCLUSIONS: This
      study has succeeded as the first of its kind to compare and contrast levels and
      sources of stress amongst an international sample. The findings indicate that
      student nurses worldwide do share much in common while still retaining individual
      cultural features relating to stress throughout their course of study.

PMID- 17559987
TI  - Influence of enteral versus parenteral nutrition on blood glucose control in
      acute pancreatitis: a systematic review.
AB  - BACKGROUND & AIMS: There is increasing evidence that tight glucose control may
      reduce infectious complications and mortality in surgical critically ill
      patients. However, data regarding the influence of artificial nutrition on
      glycemic homeostasis are limited. Our aim was to review all randomized controlled
      trials on enteral versus parenteral nutrition in acute pancreatitis to determine
      whether the route of feeding can affect the glucose control in the setting of
      this disease. METHODS: Relevant literature cited in three electronic databases
      (Cochrane Central Register of Controlled Trials, EMBASE and Medline) were
      systematically reviewed. A meta-analysis was carried out using a random-effects
      model. RESULTS: Thirteen randomized controlled trials on enteral versus
      parenteral nutrition in acute pancreatitis were identified. Seven studies were
      excluded from analysis, leaving 6 trials in which a total of 264 non-diabetic
      patients with acute pancreatitis were treated. Intake of nutrients did not differ
      among enterally and parenterally fed patients in 5 of 6 randomized controlled
      trials. Enteral nutrition reduced the risk of hyperglycemia (relative risk 0.53;
      95% confidence interval 0.29-0.98; p = 0.04) and insulin requirement (relative
      risk 0.41; 95% confidence interval 0.24-0.70; p = 0.001). CONCLUSIONS: Enteral
      nutrition, when compared with parenteral nutrition, is associated with better
      blood glucose control in patients with acute pancreatitis.

PMID- 17559988
TI  - Meningococcal carriage and immunity in western Burkina Faso, 2003.
AB  - A prospective carriage and serological study was conducted in Burkina Faso during
      the 2003 meningitis season, which was characterized by hyperendemic Neisseria
      meningitidis serogroup W135 (NmW135) and serogroup A (NmA) disease. Participants
      were evaluated five times at monthly intervals. In the presence of moderate
      NmW135 carriage, we found a low prevalence of putatively protective levels of
      specific immunoglobulin G (IgG) and serum bactericidal antibody (SBA) against
      NmW135. Specific IgG concentrations and SBA titers against NmA were relatively
      high in this recently vaccinated population, while no NmA carriage was detected.
      NmW135 carriage infrequently induced protective immunity against reference or
      homologous strains, while natural immunity against NmW135 was frequently lost. A
      vaccine that is effective against W135 will be beneficial for sub-Saharan Africa.

PMID- 17559989
TI  - Adenovirus-based vaccine prevents pneumonia in ferrets challenged with the SARS
      coronavirus and stimulates robust immune responses in macaques.
AB  - A ferret model of severe acute respiratory syndrome (SARS)-CoV infection was used
      to evaluate the efficacy of an adenovirus vaccine. Animals were subjected to
      heterologous prime-boost using vectors from human serotype 5 and chimpanzee
      derived adenoviruses (human AdHu5 and chimpanzee AdC7) expressing spike protein
      followed by intranasal challenge with SARS-CoV. Vaccination led to a substantial
      reduction in viral load and prevented the severe pneumonia seen in unvaccinated
      animals. The same prime-boost strategy was effective in rhesus macaques in
      eliciting SARS-CoV specific immune responses. These data indicate that a
      heterologous adenovirus-based prime-boost vaccine strategy could safely stimulate
      strong immunity that may be needed for complete protection against SARS-CoV
      infection.

PMID- 17559990
TI  - A dose-response evaluation of inactivated influenza vaccine given intranasally
      and intramuscularly to healthy young adults.
AB  - Epidemic influenza occurs annually throughout the world and is accompanied by
      excess morbidity and mortality. Increasing the antigen content and topical
      administration of vaccine are two strategies being explored to improve the immune
      responses to trivalent inactivated influenza vaccine (TIV). We conducted a
      randomized, double-blind, placebo-controlled trial to compare the immunogenicity
      and reactogenicity of intramuscular (IM), intranasal (IN), or combined IM and IN
      administration of a contemporary US vaccine formulation at escalating dosage
      levels in young healthy adults. Two hundred forty three healthy adults between
      the ages of 18 and 45 years received 15, 30, or 60mcg of trivalent inactivated
      influenza vaccine by either IN, IM or both routes, 120mcg of vaccine IM, or
      placebo IN and IM. All dosages and routes of vaccine administration were well
      tolerated. A bad taste and mild nasal discomfort were more likely to be reported
      when influenza vaccine was administered IN, while arm tenderness was more common
      after IM administration. Significant increases in geometric mean serum antibody
      titers in both HAI and Nt assays were seen in all of the groups receiving
      influenza vaccine for all test antigens (P<or=.025, paired t-test), except for
      the B HAI antibody titer in the group that received 30mcg IN (P=.055, paired t
      test). Postvaccination geometric mean serum antibody titers, the frequency of
      seroresponses, and the percentage achieving postvaccination serum HAI antibody
      titers of >or=32 were higher following delivery of the study vaccines by an IM
      route than by the IN route, but significant increases in serum antibody were seen
      after IN vaccination. Nasal IgA antibody responses were more common when vaccine
      was administered IN; and, when the IN dosage was increased, the primary benefit
      from IN vaccine over IM vaccine appeared to be greater induction of nasal
      secretory antibody.

PMID- 17559991
TI  - Trends in influenza immunisation amongst an elderly Australian community.
AB  - The aim of this paper is to determine the trend in influenza vaccine coverage
      among community dwelling adults in South Australia aged 65 years and over and
      compare this prevalence with national and international influenza vaccine
      coverage. Immunisation prevalence has been measured in South Australia (SA) since
      1993 using face to face surveys and Computer Assisted Telephone Interviewing
      (CATI). There has been an increasing trend in influenza immunisation in South
      Australia over the last 12 years among community dwelling adults aged 65 years
      and over. This indicates that policies and campaigns have impacted positively on
      influenza vaccine uptake.

PMID- 17559992
TI  - Quantitative methylation analysis of resection margins and lymph nodes in oral
      squamous cell carcinoma.
AB  - Resection is the preferred treatment for oral squamous cell carcinoma, and
      pathological staging of the resected specimen is crucial. The role of molecular
      biology in the diagnosis of minimal residual disease has not been fully
      investigated and may improve staging. Multiple adjacent specimens were taken from
      the tumour, the invasive front, the surgical margin, and the lymph nodes of 20
      specimens from patients with oral cancer. Bisulphite-treated DNA from these
      specimens was assayed quantitatively with pyrosequencing methylation assays (PMA)
      of CpG islands within the gene promoters of the p16 and CYGB genes. Results were
      recorded with histopathological results, and compared with clinical outcome.
      Biological and technical replicates confirmed the reliability of the techniques.
      PMA upgraded 13 of the 20 surgical margins, 6 of which subsequently had a
      recurrent tumour. Not all of these recurrences were predicted and the effects of
      adjuvant treatment make firm conclusions difficult.

PMID- 17559993
TI  - Widespread oral and oropharyngeal mucosal oedema induced by ecstasy (MDMA): A
      case for concern.
AB  - We describe an unusual adverse reaction that was probably caused by taking
      ecstasy: the patient developed widespread oral and oropharyngeal mucosal oedema,
      which was triggered after he had taken ecstasy and alcohol. The reaction to this
      could have been fatal.

PMID- 17559994
TI  - Grain size partitioning of platinum-group elements in road-deposited sediments:
      implications for anthropogenic flux estimates from autocatalysts.
AB  - Twelve road-deposited sediment samples were analyzed for platinum-group elements
      (PGEs) and Pb in the <63 microm fraction of an urban watershed in Hawaii. Three
      samples were further fractionated into five size classes, from 63-125 microm to
      1000-2000 microm, and these were analyzed for PGEs and Pb. Concentrations in the
      <63 microm fraction reached 174 microg/kg (Pt), 101 microg/kg (Pd), 16 microg/kg
      (Rh), and 1.3 microg/kg (Ir). Enrichment ratios followed the sequence
      Rh>Pt=Pd>Ir. Iridium was geogenic in origin, while the remaining PGEs indicated
      significant anthropogenic contamination. Palladium, Pt and Rh concentrations and
      enrichment signals were consistent with PGE bivariate ratios and PGE partitioning
      in three-way catalysts. Size partitioning indicated that the <63 microm fraction
      had the lowest PGE concentrations and mass loading percentages. These data
      suggest that autocatalyst PGE flux estimates into the environment will be
      significantly underestimated if only a fine grain size fraction is analyzed.

PMID- 17559995
TI  - Is the integration of hormesis and essentiality into ecotoxicology now opening
      Pandora's Box?
AB  - Hormesis and essentiality are likely real and common effects at the level of the
      individual. However, the widespread incorporation of stimulatory effects into
      applications of ecotoxicology requires the acceptance of assumptions, value
      judgements and possibly lowering of water/sediment quality standards. There is
      also currently little data appropriate for considering hormetic effects in the
      ecotoxicological context. Except perhaps in the case of fitting concentration
      response curves, it is not clear that incorporation of hormetic and essentiality
      type responses into ecotoxicology is necessary. Furthermore, its incorporation
      presents considerable intellectual and practical changes for ecotoxicology and
      could have unanticipated consequences.

PMID- 17559996
TI  - How might we understand men's health better? Integrating explanations from
      critical studies on men and inequalities in health.
AB  - For researchers interested in understanding men's health, there are two main
      literatures to harvest. The first is research on men's health arising from the
      study of men and masculinities. The second is the broader study of inequalities
      in health, including gender inequalities in health. However, these literatures
      have remained distinct. This paper seeks to develop a model of understanding
      men's health from both of these literatures. In order to achieve this
      integration, this paper argues that studies of men's health should be based on
      'critical studies on men' which emerges from feminist theory. Critical studies on
      men's health is then integrated into the broader explanatory options identified
      in the health inequality literature in order to provide a more fulsome account of
      variance within men's health and between the health status of men and women.
      Given the amenability of men's health issues to interrogation within this
      resulting framework, it is argued that the inequalities literature should start
      to include men's health issues in its work.

PMID- 17559997
TI  - Association between major Multidrug Resistance 1 (MDR1) gene polymorphisms and
      plasma concentration of prolactin during risperidone treatment in schizophrenic
      patients.
AB  - An in vitro study has suggested that risperidone is a substrate of P
      glycoprotein, which is coded by MDR1gene. The rate of P-glycoprotein efflux
      transport can mediate brain penetration of lipophilic drugs. We therefore studied
      the effects of major polymorphisms of MDR1 gene on plasma concentrations of
      prolactin. Subjects included 175 schizophrenic patients (68 males, 107 females)
      who were receiving 3 mg of risperidone twice daily for at least 4 weeks. Sample
      collections were conducted 12 h after the bedtime dosing. The plasma
      concentrations of prolactin in females were significantly higher than in males
      (54.3+/-27.2 versus 126.8+/-70.2 ng/ml, p<0.001). There was no difference in mean
      (+/-SD) plasma concentration of prolactin between C3435T genotypes [C/C, C/T,
      T/T; 62.3+/-33.3, 49.4+/-15.6, 53.2+/-33.2 ng/ml, ns] or G2677T/A genotypes [G/G,
      G/T or A, T or A/T or A; 58.0+/-27.7, 58.5+/-35.0, 46.1+/-20.7 ng/ml, ns] in
      males nor between C3435T genotypes (123.6+/-65.0, 127.8+/-79.2, 130.4+/-49.7
      ng/ml, ns) or G2677T/A genotypes (123.3+/-67.0, 97.7+/-71.2, 144.9+/-69.9 ng/ml,
      ns) in females. Multiple regression analyses including plasma drug concentration
      and age revealed that plasma concentration of prolactin correlated with gender
      (standardized beta=0.540, p<0.001) and negatively with age (standardized beta=
      0.183, p<0.01). No correlations were found between prolactin concentration and
      MDR1 genotypes. These findings suggest that prolactin concentrations in females
      are much higher than in males but the major MDR1 variants are not associated with
      the plasma concentration of prolactin.

PMID- 17559998
TI  - Intake of chemical contaminants through fish and seafood consumption by children
      of Catalonia, Spain: health risks.
AB  - The intake of arsenic (As), cadmium (Cd), mercury (Hg), lead (Pb),
      polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs), polychlorinated
      biphenyls (PCBs), polychlorinated naphthalenes (PCNs), polybrominated
      diphenylethers (PBDEs), polychlorinated diphenylethers (PCDEs),
      hexachlorobenzene, and polycyclic aromatic hydrocarbons through fish and seafood
      consumption by children of Catalonia, Spain, was assessed. In 2005, samples of
      the 14 most consumed marine species in Catalonia were randomly acquired in
      various cities of the country. Analysis of the above chemical contaminants were
      determined according to the appropriate analytical techniques and the daily
      intakes were estimated. For most pollutants, intake was higher in boys than in
      girls. Average exposure of children to contaminants through fish and seafood
      consumption did not exceed the respective tolerable daily intake of those
      pollutants for which it has been already established (metals, PCDD/Fs plus dioxin
      like PCBs, HCB, and PAHs). In relation to body weight, intake by children of most
      contaminants was higher than that found for other age groups of the general
      population of Catalonia.

PMID- 17559999
TI  - Antioxidant and prooxidant effects of quercetin on glyceraldehyde-3-phosphate
      dehydrogenase.
AB  - Anti- and prooxidant properties of quercetin under different conditions were
      investigated using glyceraldehyde-3-phosphate dehydrogenase, a glycolytic enzyme
      containing essential cysteine residues. Quercetin was shown to produce hydrogen
      peroxide in aqueous solutions at pH 7.5, this resulting in the oxidation of the
      cysteine residues of the enzyme. Quercetin significantly increased oxidation of
      GAPDH observed in the presence of ferrous ions, particularly when FeSO(4) was
      added to the solution containing GAPDH and quercetin. The results suggest the
      formation of hydroxyl radical in the case of the addition of FeSO(4) to a
      quercetin solution. At the same time, quercetin protects GAPDH from oxidation in
      the presence of ascorbate and Fe(3+). In the absence of metals, quercetin
      protects SH-groups of GAPDH from oxidation by the superoxide anion generated by
      the system containing xanthine/xanthine oxidase.

PMID- 17560000
TI  - PF2401-SF, standardized fraction of Salvia miltiorrhiza and its constituents,
      tanshinone I, tanshinone IIA, and cryptotanshinone, protect primary cultured rat
      hepatocytes from bile acid-induced apoptosis by inhibiting JNK phosphorylation.
AB  - Bile acid-induced hepatocyte apoptosis plays an important role in cholestatic
      liver disease, and the role of apoptosis may be of therapeutic interest in
      preventing liver disease. The dried root of Salvia miltiorrhiza Bunge (Labiatae)
      has been used traditionally to treat liver diseases. We investigated the
      antiapoptotic effects of a standardized fraction of S. miltiorrhiza (PF2401-SF)
      and its components, tanshinone I, tanshinone IIA, and cryptotanshinone, in
      primary cultured rat hepatocytes. PF2401-SF was enriched with tanshinone I
      (11.5%), tanshinone IIA (41.0%), and cryptotanshinone (19.1%).
      Glycochenodeoxycholic acid (GCDC)-induced apoptosis, as shown by DNA
      fragmentation, poly(ADP-ribose) polymerase cleavage, and activation of caspases
      8, -9, and -3. PF2401-SF and its components, tanshinone I, tanshinone IIA, and
      cryptotanshinone showed antiapoptotic activity. Treatment with PF2401-SF or with
      its components significantly inhibited the generation of intracellular reactive
      oxygen species. Hydrophobic bile acids activate c-Jun-NH(2)-terminal kinase
      (JNK), p38 mitogen-activated protein kinases (MAPK), and extracellular signal
      regulated kinase 1/2, and PF2401-SF inhibited the phosphorylation of JNK and p38.
      All three components of PF2401-SF inhibited JNK phosphorylation. Addition of
      inhibitors of MAPK showed that inhibition of JNK decreased apoptosis. These data
      indicate that PF2401-SF and its components protect hepatocytes from GCDC-induced
      apoptosis in vitro by inhibiting JNK.

PMID- 17560002
TI  - Effect of zinc supplementation on bone metabolism in male rats chronically
      exposed to cadmium.
AB  - The aim of the present study is to investigate, based on the rat model of
      moderate and relatively high human exposure to cadmium (Cd), whether zinc (Zn)
      supplementation may prevent Cd-induced disorders in bone metabolism. For this
      purpose, male Wistar rats received Cd (5 and 50mg/l) or/and Zn (30 and 60mg/l) in
      drinking water for 6 and 12 months. Bone densitometry and biochemical markers of
      bone turnover were used to assess the effects of Cd or/and Zn. Bone mineral
      content (BMC) and density (BMD) were measured in the femur. Serum osteocalcin
      (OC) and alkaline phosphatase in trabecular (bT-ALP) and cortical (bC-ALP) bone
      were determined as bone formation markers, and carboxy-terminal cross-linking
      telopeptides of type I collagen (CTX) in serum were measured as bone resorption
      marker. Serum concentration of calcium (Ca) and its renal handling, as well as Zn
      and Cd concentrations in the serum/blood, urine and femur were evaluated as well.
      The exposure to 5 and 50mg Cd/l (0.340+/-0.026 and 2.498+/-0.093mg Cd/kg body
      wt/24h, respectively), in a dose and duration dependent manner, affected bone
      turnover (inhibited bone formation and stimulated its resorption) and disturbed
      bone mineralization (decreased BMC, BMD and Zn concentration). Zn supply at the
      concentration of 30 and 60mg/l (1.904+/-0.123 and 3.699+/-0.213mg/kg body wt/24h,
      respectively) during Cd exposure influenced the Cd-induced disorders in bone
      metabolism. Zn administration to the Cd-exposed rats enhanced the bone ALP
      activity and prevented Cd-induced bone resorption, but had no statistically
      significant effect on BMC and BMD; however, mean values of the densitometric
      parameters in the rats receiving both Cd and Zn were higher than in those treated
      with Cd alone. Moreover, Zn supplementation at both levels of Cd exposure was
      found to prevent Cd accumulation in the femur and the Cd-induced decrease in bone
      Zn concentration. The results of the present study allow the conclusion that Zn
      supplementation during Cd exposure may partly protect from disorders in bone
      metabolism. The influence of Zn may be accompanied by its ability to prevent Cd
      induced Zn deficiency and to decrease Cd accumulation in bone tissue. The
      findings seem to indicate that enhanced dietary intake of Zn in subjects
      chronically exposed to moderate and relatively high Cd levels may have a
      protective influence on the skeleton.

PMID- 17560001
TI  - Comparative effects of aluminum and ouabain on synaptosomal choline uptake,
      acetylcholine release and (Na+/K+)ATPase.
AB  - Closing the gap between adverse health effects of aluminum and its mechanisms of
      action still represents a huge challenge. Cholinergic dysfunction has been
      implicated in neuronal injury induced by aluminum. Previously reported data also
      indicate that in vivo and in vitro exposure to aluminum inhibits the mammalian
      (Na(+)/K(+))ATPase, an ubiquitous plasma membrane pump. This study was undertaken
      with the specific aim of determining whether in vitro exposure to AlCl(3) and
      ouabain, the foremost utilized selective inhibitor of (Na(+)/K(+))ATPase, induce
      similar functional modifications of cholinergic presynaptic nerve terminals, by
      comparing their effects on choline uptake, acetylcholine release and
      (Na(+)/K(+))ATPase activity, on subcellular fractions enriched in synaptic nerve
      endings isolated from rat brain, cuttlefish optic lobe and torpedo electric
      organ. Results obtained show that choline uptake by rat synaptosomes was
      inhibited by submillimolar AlCl(3), whereas the amount of choline taken up by
      synaptosomes isolated from cuttlefish and torpedo remained unchanged. Conversely,
      choline uptake was reduced by ouabain to a large extent in all synaptosomal
      preparations analyzed. In contrast to ouabain, which modified the K(+)
      depolarization evoked release of acetylcholine by rat, cuttlefish and torpedo
      synaptosomal fractions, AlCl(3) induced reduction of stimulated acetylcholine
      release was only observed when rat synaptosomes were challenged. Finally, it was
      observed that the aluminum effect on cuttlefish and torpedo synaptosomal
      (Na(+)/K(+))ATPase activity was slight when compared to its inhibitory action on
      mammalian (Na(+)/K(+))ATPase. In conclusion, inhibition of (Na(+)/K(+))ATPase by
      AlCl(3) and ouabain jeopardized the high-affinity (Na(+)-dependent, hemicholinium
      3 sensitive) uptake of choline and the Ca(2+)-dependent, K(+) depolarization
      evoked release of acetylcholine by rat, cuttlefish and torpedo synaptosomal
      fractions. The effects of submillimolar AlCl(3) on choline uptake and
      acetylcholine release only resembled those of ouabain when rat synaptosomes were
      assayed. Therefore, important differences were found between the species
      regarding the cholinotoxic action of aluminum. The variability of
      (Na(+)/K(+))ATPase sensitivity to aluminum of cholinergic neurons might
      contribute to their differential susceptibility to this neurotoxic agent.

PMID- 17560003
TI  - Oleic acid and docosahexaenoic acid cause an increase in the paracellular
      absorption of hydrophilic compounds in an experimental model of human absorptive
      enterocytes.
AB  - Surface active compounds present in food possibly have the ability to enhance the
      absorption of water soluble toxic agents. Therefore, we investigated whether
      fatty acids such as oleic acid and docosahexaenoic acid (DHA), both commonly
      present in food, negatively affect the integrity of tight junctions (TJ) in the
      intestinal epithelium and thereby increase the absorption of poorly absorbed
      hydrophilic substances. Caco-2 cells, which are derived from human absorptive
      enterocytes, were grown on permeable filters for 20-25 days. Differentiated cell
      monolayers were apically exposed for 90min to mannitol in emulsions of oleic acid
      (5, 15 or 30mM) or DHA (5, 15 or 30mM) in an experimental medium with or without
      Ca(2+) and Mg(2+). Absorption of (14)C-mannitol increased and trans-epithelial
      electrical resistance (TEER) decreased in cell monolayers exposed to oleic acid
      and DHA, compared to controls. Cytotoxicity, measured as leakage of LDH, was
      higher in groups exposed to 30mM oleic acid and all concentrations of DHA.
      Morphology of the cell monolayers was studied by using fluorescence microscopy.
      Exposure of cell monolayers to 5mM DHA for 90min resulted in a profound
      alteration of the cell-cell contacts as detected by staining the cells for beta
      catenin. Oleic acid (30mM) treatment also induced dissolution of the cell-cell
      contacts but the effect was not as pronounced as with DHA. Cell monolayers were
      also exposed for 180min to 250nM cadmium (Cd) in emulsions of oleic acid (5 or
      30mM) or DHA (1 or 5mM), in an experimental medium with Ca(2+) and Mg(2+).
      Retention of Cd in Caco-2 cells was higher after exposure to 5mM oleic acid but
      lower after exposure to 30mM oleic acid and DHA. Absorption of Cd through the
      monolayers increased after DHA exposure but not after exposure to oleic acid. Our
      results indicate that fatty acids may compromise the integrity of the intestinal
      epithelium and that certain lipids in food may enhance the paracellular
      absorption of poorly absorbed hydrophilic substances.

PMID- 17560004
TI  - An open issue: the inner mitochondrial membrane (IMM) as a free boundary problem.
AB  - The inner mitochondrial membrane (IMM) is structured in cristae, which
      contributes to the best functioning of ions and adenylates exchange between the
      matrix and the intermembrane space. The central hypothesis of this paper is that
      the cristae structure favours a minimal mean free path of adenylates between
      translocation sites (translocase/ANT sites) and metabolic sites (ATPase sites).
      We propose a mathematical model and then give simulations. Based on simple
      hypotheses about cristae growth, they show that we can account for the major
      features of the IMM organization and functioning by minimizing the mean
      interdistance between ADP/ATP translocation and transformation sites.

PMID- 17560005
TI  - Is CPR quality improving? A retrospective study of out-of-hospital cardiac
      arrest.
AB  - AIM OF THE STUDY: To evaluate the quality of cardiopulmonary resuscitation (CPR)
      performed by a physician-manned ambulance, and assess whether it changed with
      time influenced by developing scientific evidence and guideline changes.
      MATERIALS AND METHODS: A retrospective, observational study of all cardiac arrest
      patients (except trauma) older than 18 years treated between May 2003 and
      December 2006 by the physician-manned ambulance in Oslo. CPR quality was assessed
      from continuous electronic recordings from the defibrillators (LIFEPAK 12, Physio
      Control or a modified Heartstart 4000, Philips Medical Systems). Ventilations
      were assessed from changes in transthoracic impedance, chest compressions from
      transthoracic impedance for LIFEPAK 12 and from an accelerometer for Heartstart
      4000 (nine patients). Values are given as mean+/-S.D. and differences analysed
      with ANOVA and unpaired Student's t-test with Bonferroni correction. RESULTS:
      Forty-eight of 169 consecutive cases were excluded from CPR quality analysis, 47
      due to missing defibrillator data and one due to a short arrest time (<1min).
      Hands-off intervals (fraction of time without spontaneous circulation where no
      chest compressions are given) were reduced from 0.18+/-0.11 in 2003 to 0.10+/
      0.06 in 2006 (p=0.03). Compression and ventilation rates were significantly
      reduced from 122+/-12 and 16+/-3min(-1), respectively in 2003 to 111+/-10 and
      12+/-3 in 2006 (p<0.0001 and p=0.001). In 2003-2004 10% were discharged alive
      versus 16% in 2005-2006 (p=0.3, Chi-square test). CONCLUSION: High quality CPR is
      achievable out-of-hospital, and the improvement with time could reflect
      developing scientific evidence focusing on reducing hands-off intervals and
      hyperventilation.

PMID- 17560006
TI  - Pregnancy in patients on chronic dialysis: a single center experience and
      combined analysis of reported results.
AB  - OBJECTIVE(S): Pregnancy is rare in patients on chronic dialysis, with only a 30
      50% rate of successful delivery reported in a previous review article. The
      pregnancy outcome has improved in recent decades, but data on pregnancy outcome
      are limited due to the small sample size of previous case series. This study
      investigated the pregnancy outcome in patients on chronic dialysis over the past
      15 years in a single center, and also performed a combined analysis of results of
      individual cases from previously reported series to obtain overall estimates of
      rates of successful delivery. STUDY DESIGN: Medical records for a total of 13
      pregnancies in 13 women undergoing chronic dialysis (10 on hemodialysis and 3 on
      peritoneal dialysis) during the period from 1990 to 2006 in our hospital were
      retrospectively reviewed. Data on the changes in dialysis regimen, medical
      complications, obstetric conditions, and perinatal problems were collected. An
      electronic search of PubMed identified 10 case series studies and 12 case reports
      published after 1990 with adequate individual information available. Pooled data
      from a total of 131 cases, including our patients (117 hemodialysis and 14
      peritoneal dialysis), were analyzed using the chi(2)-test and the t-test to
      compare the rate of successful delivery and birth weight in the hemodialysis
      group and the peritoneal dialysis group, and in pregnancies with conception prior
      to and those with conception after starting dialysis. RESULTS: Among the 10
      pregnant women who decided to continue their pregnancies in our hospital, 5
      delivered live newborns and 5 pregnancies ended with intra-uterine fetal demise
      or neonatal death. The overall rate of successful delivery was 70.9% (83 out of
      117) in patients on hemodialysis and 64.2% (9/14) in patients on peritoneal
      dialysis. The birth weight for these groups was 1483+/-116 and 1623+/-320 g,
      respectively. The difference in the rates of successful delivery in these two
      groups was not significant (p=0.61). However, the birth weight was significantly
      greater in patients who conceived after than those who conceived prior to
      starting hemodialysis (1529+/-132 g versus 1245+/-200 g; p=0.04). CONCLUSIONS:
      This study found that the outcome of pregnancy on chronic dialysis has improved
      in recent decades, but our study showed no significant difference in the rate of
      successful delivery between patients on hemodialysis and those on peritoneal
      dialysis.

PMID- 17560007
TI  - A theoretical study on activation of transcription factor modulated by
      intracellular Ca2+ oscillations.
AB  - This work presents both deterministic and stochastic models of genetic expression
      modulated by intracellular calcium (Ca2+) oscillations, based on macroscopic
      differential equations and chemical Langevin equations, respectively. In
      deterministic case, the oscillations of intracellular Ca2+ decrease the effective
      Ca2+ threshold for the activation of transcriptional activator (TF-A). The
      average activation of TF-A increases with the increase of the average amplitude
      of intracellular Ca2+ oscillations, but decreases with the increase of the period
      of intracellular Ca2+ oscillations, which are qualitatively consistent with the
      experimental results on the gene expression in lymphocytes. In stochastic case,
      it is found that a large internal fluctuation of the biochemical reaction can
      enhance gene expression efficiency specifically at a low level of external
      stimulations or at a small rate of TF-A dimer phosphorylation activated by Ca2+,
      which reduces the threshold of the average intracellular Ca2+ concentration for
      gene expression.

PMID- 17560008
TI  - Modulation of T-effector function by imatinib at the level of cytokine secretion.
AB  - OBJECTIVE: Recently, evidence was provided, that the selective tyrosine kinase
      inhibitor imatinib mesylate (imatinib) has immunomodulatory or suppressive
      effects. However, the discussion about imatinib's influence on immune cells is
      still controversial. The aim of this study was to clarify the effect of imatinib
      on CD8+ and CD4+ T-cell effector functions. MATERIALS AND METHODS: For analyzing
      T-cell effector functions T-cell receptor-transgenic ovalbumin-specific CD8+ T
      cells and in vivo primed CD4+ Th1 cells were used. T-cell effector functions were
      analyzed on the level of antigen responsiveness by intracellular cytokine
      staining, by measuring cytokine secretion in an interferon-gamma (IFN-gamma)
      enzyme-linked immunosorbent assay and by detecting cytotoxicity using the
      fluorescein-activated cell sorting-based fluorometric assessment of T-lymphocyte
      antigen-specific lysis assay. RESULTS: It was demonstrated that imatinib inhibits
      antigen-specific IFN-gamma secretion of both CD4+ and CD8+ T-effector cells at
      therapeutically relevant concentrations, while T cells remain responsive. The
      decrease of IFN-gamma production was not due to the loss of T-cell viability.
      Further, it was shown that the effector T cells are modulated rather than
      suppressed, because the cytolytic functions of CD8+ cytotoxic T cells were not
      altered. Residual cytolytic activity in the presence of imatinib was not due to
      FasL interaction. CONCLUSIONS: These experiments provide evidence for a
      therapeutically relevant modulation of T-cell effector functions by imatinib.
      This might open a possible applicability of imatinib in various autoimmune and
      inflammatory diseases, including multiple sclerosis and rheumatoid arthritis.

PMID- 17560009
TI  - Vav promoter-tTA conditional transgene expression system for hematopoietic cells
      drives high level expression in developing B and T cells.
AB  - OBJECTIVE: We previously showed that Vav promoter-tetracycline transactivator
      (Vav-tTA)-driven tetracycline-regulated element (TRE)-NRAS(V12) expression
      resulted in mastocytosis development in mice. To investigate which hematopoietic
      cells express TRE-driven transgenes when combined with Vav-tTA, we assayed
      hematopoietic cells, including bone marrow-derived mast cells (BMMC) and CD34
      positive hematopoietic progenitor cells (HPC) as well as myeloid and lymphoid
      lineages. To determine if suppression of NRAS(V12) expression early in life would
      delay mastocytosis we treated developing and juvenile mice with doxycycline
      (Dox). MATERIALS AND METHODS: Vav-tTA-driven luciferase expression was assayed by
      live mouse imaging and relative light unit measurement before or after treating
      Vav-tTA and TRE-luciferase (TRE-Luc) cotransgenic mice with Dox. Magnetic cell
      sorting and fluorescence-activating cell sorting methods were used to sort
      hematopoietic cells. To suppress TRE-mediated luciferase or NRAS(V12) expression
      in Vav-tTA cotransgenic mice, we added Dox to the drinking water. RESULTS: B
      cells in the bone marrow and T cells in the thymus expressed Vav-tTA-driven
      luciferase at much higher levels than in myeloid cells, BMMC, and CD34-positive
      HPC, which showed relatively low levels. Dox treatment completely eliminated the
      luciferase expression from all hematopoietic cells. Repression of TRE-NRAS(V12)
      expression early in life was sufficient to increase the latency of mastocytosis
      development. CONCLUSION: The Vav-tTA transgenic line will be very useful for
      conditional transgene expression in developing B and T cells. Vav-tTA-driven
      NRAS(V12) expression is sufficient for mastocytosis development, but not for
      myeloid leukemia. Lymphoid cells are resistant to NRAS(V12) transformation
      despite high level of expression.

PMID- 17560010
TI  - Antiapoptotic cytokines in combination with pegfilgrastim soon after irradiation
      mitigates myelosuppression in nonhuman primates exposed to high irradiation dose.
AB  - OBJECTIVE: Preservation of hematopoietic stem and progenitor cells from early
      radiation-induced apoptosis is the rationale for emergency antiapoptotic cytokine
      therapy (EACK) after radiation accidents. This strategy is based on the
      combination of stem cell factor + Flt3-ligand + thrombopoietin + interleukin 3
      (SFT3). The long-term safety and efficacy of EACK in managing severe radiation
      exposure were evaluated. MATERIAL AND METHODS: Early administration of SFT3 +
      pegfilgrastim was assessed in 7-Gy gamma total body-irradiated (TBI) monkeys.
      Efficiency of delayed administration was also addressed after 5-Gy TBI. RESULTS:
      Here we showed that a single, intravenous injection of SFT3 2 hours after 7-Gy
      TBI reduced the period of thrombocytopenia (platelet count <20 x 10(9)/L: 0.8 +/-
      1.5 day vs 23.8 +/- 15.9 days in controls; p < 0.05) and blood transfusion needs.
      Moreover, addition of pegfilgrastim to SFT3 treatment shortened the period of
      neutropenia compared with SFT3 and control groups (neutrophil count <0.5 x
      10(9)/L: 7 +/- 1.4 days vs 13 +/- 3.2 days and 15.2 +/- 1.5 days; p < 0.05). In
      both SFT3 groups, bone marrow activity recovered earlier and, in contrast with
      controls, platelet count returned to baseline values from 250 days after
      irradiation. Furthermore, delayed (48 hours) single SFT3 administration in 5-Gy
      irradiated monkeys significantly reduced thrombocytopenia compared to controls.
      Finally, SFT3 did not increase frequency of total chromosome translocations
      observed in the blood lymphocytes of controls 1 year after 5 Gy TBI. CONCLUSION:
      These results suggest the safety and efficacy of EACK in managing severe
      radiation exposure.

PMID- 17560011
TI  - Leukemogenic AML1-ETO fusion protein increases carcinogen-DNA adduct formation
      with upregulated expression of cytochrome P450-1A1 gene.
AB  - OBJECTIVE: AML1-ETO fusion protein is a product of chromosome translocation
      t(8;21) frequently occurred in acute myeloid leukemia (AML), but its sole
      expression appears to fail to cause overt leukemia in vivo. In this study, we
      investigated whether AML1-ETO expression impinged on action of chemical
      carcinogens-DNA adduct formation. MATERIALS AND METHODS: AML1-ETO fusion protein
      was conditionally induced in engineered U937-A/E 9/14/18 cells. The formation of
      polycyclic aromatic hydrocarbon (PAH)-DNA adducts and the expression of PAH
      metabolizing enzymes cytochrome P450 (CYP) 1A1 and arylhydrocarbon receptor (AhR)
      were detected by Western blot and/or quantitative RT-PCR. Luciferase reporter
      system was used to detect the regulation of AML1-ETO on CYP1A1 transcription.
      RESULTS: Our results showed that AML1-ETO induction significantly increased the
      formation of carcinogen benzopyrene-DNA adducts in leukemic cells. In line with
      the effect, we also found that AML1-ETO induction upregulated CYP1A1 expression,
      which was dependent on AML1-binding motif in the promotor of CYP1A1 gene.
      Additionally, AML1-ETO protein also increased AhR expression, a ligand-activated
      transcription factor that mediates PAHs-induced CYP1A1 gene expression.
      CONCLUSION: These data, combined with its inhibitory effect on DNA repair as
      reported previously, propose that the presence of AML1-ETO increases the
      susceptibility of cells to chemical carcinogens, which favors the development of
      additional genetic alterations.

PMID- 17560012
TI  - Global proteome profiling of NPM/ALK-positive anaplastic large cell lymphoma.
AB  - OBJECTIVE: Constitutive overexpression of nucleophosmin/anaplastic lymphoma
      kinase (NPM/ALK) is a key oncogenic event in anaplastic large cell lymphomas
      (ALCL) that carry the t(2;5)(p23;q35) translocation. Global proteomic analysis of
      NPM/ALK-positive ALCL would improve understanding of the disease pathogenesis and
      yield new candidate targets for novel treatment and diagnostic strategies.
      MATERIALS AND METHODS: To comprehensively determine the inventory of proteins
      from NPM/ALK-positive ALCL SUDHL-1 cells, the membrane, cytoplasm, and nuclear
      subcellular fractions were resolved by one-dimensional sodium dodecyl sulfate
      polyacrylamide gel electrophoresis (SDS-PAGE) and analyzed using liquid
      chromatography-tandem mass spectrometry (LC-MS/MS). The MS spectra were
      interpreted using SEQUEST to search the electronic UniProt protein database, and
      analyzed by ProteinProphet and INTERACT. RESULTS: A total of 623 proteins
      consisting of 210 membrane, 229 cytoplasm, and 184 nuclear proteins were
      identified with a <or=5% error rate. Extensive annotation and systematic
      examination of the literature for information on 209 representative proteins
      indicated that 19.9% were reported to be expressed in T cells and 44.7% were
      reported to have important function in cancers, while only 4.3% were reported to
      be involved in ALCL pathogenesis. Categorization of proteins into functional
      groups was performed using GOMiner. A subset of the identified proteins was
      confirmed by Western blots and immunohistochemistry of tissue samples.
      CONCLUSION: We present an extensive catalog of proteins expressed by NPM/ALK
      positive ALCL. This study illustrates the potential for novel pathogenetic
      discovery in NPM/ALK-positive ALCL and the utility of combining cellular
      subfractionation, 1D SDS-PAGE, and LC-MS/MS for the comprehensive protein
      analysis of lymphoma.

PMID- 17560013
TI  - Measuring bed shear stress along vegetated river beds using FST-hemispheres.
AB  - The measurement of the bed shear stress along vegetated river beds is essential
      for accurately predicting the water level, velocity and solute and sediment
      transport fluxes in computational hydroenvironmental models. Details are given
      herein of an experimental and theoretical study to determine the bed boundary
      shear stress along vegetated river beds introducing a novel field measuring
      method, namely the FliessWasserStammtisch (FST)-hemispheres. Although
      investigations have been conducted previously for sedimentary channels using the
      FST-hemispheres, this preliminary study is thought to be the first time that such
      hemispheres have been used to investigate the bed shear stresses in vegetated
      channels. FST-hemispheres were first developed by Statzner and Muller [1989.
      Standard hemispheres as indicators of flow characteristics in lotic benthos
      research. Freshwater Biology 21, 445-459] to act as an integrated indicator of
      the gross hydrodynamic stresses present near the bed. Test and validation data
      were found to be at least of the same order of magnitude for the stresses
      predicted from literature for sedimentary channels, with this study establishing
      the commencement of a database of calibrated FST-hemisphere laboratory data for
      vegetated channel beds. In a series of experiments, depths ranging from 0.1 to
      0.28 m were considered, equating directly to comparable conditions in small
      rivers or streams. The results of this study provide a basis for enabling the FST
      hemispheres to be used to evaluate the boundary shear stress for a wider range of
      applications in the future, including vegetated river beds.

PMID- 17560014
TI  - Editorial comment on: Adjustable suburethral sling (Male Remeex System) in the
      treatment of male stress urinary incontinence: a multicentric european study.

PMID- 17560015
TI  - Re: Derya Tilki, Ergin Kilic, Robert Tauber, Dietrich Pfeiffer, Christian G.
      Stief, Roland Tauber and Suleyman Ergun. The complex structure of the smooth
      muscle layer of spermatic veins and its potential role in the development of
      varicocele testis. Eur Urol 2007;51:1402-10.

PMID- 17560016
TI  - Adjustable suburethral sling (male remeex system) in the treatment of male stress
      urinary incontinence: a multicentric European study.
AB  - OBJECTIVE: To evaluate the effectiveness of a readjustable sling for the
      treatment of male stress urinary incontinence (SUI). MATERIALS AND METHODS:
      Between October 2002 and August 2005, 51 male patients with mild to severe SUI
      were prospectively operated with the use of a readjustable sling (MRS) at seven
      different European hospitals: Spain (2), Italy (2), Greece (1), Germany (1), and
      Portugal (1). The origin of incontinence was radical prostatectomy in 43 cases,
      TUR in 4, and open prostatectomy in another 4. Duration of incontinence ranged
      from 1 to 10 yr with an average of 3.5 yr. RESULTS: All patients but 5 were
      regulated during the early postoperative period; 44 patients (including all 5 not
      regulated during the early period) required a second regulation under local
      anaesthesia between 1 to 4 mo after surgery, and 17 other patients required more
      than one delayed regulation. After that, 33 patients (64.7%) were considered
      cured (25 of them wore no pads at all, and 8 used small pads or sanitary napkins
      for security but normally remained dry); another 10 cases showed important
      improvement (19.6%); and only 8 patients remain unchanged (15.7%). The average
      follow-up time was 32 mo (range: 16-50). The mesh was removed in 1 case owing to
      urethral erosion and the varitensor in 2 cases owing to infection. There were
      five (9.8%) uneventful intraoperative bladder perforations at the postoperative
      period, and there were three mild perineal haematomas (5.9%). Most patients felt
      perineal discomfort or pain, which was easily treated with oral medications.
      CONCLUSIONS: The MRS((R)) allowed postoperative readjustment of the suburethral
      sling pressure at the immediate or midterm postoperative period, which allowed
      the achievement of good midterm results in almost 85% of patients without
      significant postoperative complications.

PMID- 17560018
TI  - Nuclear translocation of apoptosis inducing factor is associated with cisplatin
      induced apoptosis in LNCaP prostate cancer cells.
AB  - Prostate cancer (PC) is considered resistant to cisplatin chemotherapy. In order
      to identify novel causes of resistance to cisplatin, we explored the role of
      Apoptosis Inducing Factor (AIF) that mediates caspase independent apoptosis in
      cisplatin induced cell death in PC. Similar to treatment with pancaspase
      inhibitor Z-VAD-fmk, cisplatin induced apoptosis in LNCaP cells was inhibited by
      AIF inhibitor N-acetyl-L-cysteine (NAC), treatment of LNCaP cells with NAC
      prevented AIF translocation to the nucleus and over-expression of recombinant AIF
      gene increased apoptosis. Our results suggest that AIF is associated with
      cisplatin induced apoptosis in PC.

PMID- 17560019
TI  - Development and in vitro validation of anti-mesothelin biobodies that prevent
      CA125/Mesothelin-dependent cell attachment.
AB  - Preventing peritoneal implantation of carcinoma cells could prolong ovarian
      cancer patient remission and survival. Peritoneal cells constitutively express
      mesothelin, a ligand for CA125 that is expressed by tumor cells. Thus blocking
      CA125/mesothelin-dependent cell attachment may prevent or delay peritoneal
      metastatic recurrence. We developed a high-throughput screening system for
      reagents able to block CA125/mesothelin-dependent cell attachment with a
      sensitive quantitative readout. Using a novel yeast-expression system to produce
      secreted, in vivo biotinylated proteins and biobodies (Bbs), we generated anti
      mesothelin Bbs. Anti-mesothelin Bbs derived from high affinity yeast-display scFv
      detected both membrane-bound and soluble mesothelins and inhibited
      CA125/mesothelin-dependent cell attachment.

PMID- 17560020
TI  - Preparation of the diphenylcarbazone-functionalized silica gel and its
      application to on-line selective solid-phase extraction and determination of
      mercury by flow-injection spectrophotometry.
AB  - A new solid-phase extractor, diphenylcarbazone-functionalized silica gel has been
      synthesized and confirmed by IR and Raman spectrometry. The new solid-phase
      extractor is found to be stable in 1-6 mol L(-1) HCl or H(2)SO(4), and also in
      common organic solvents. It can be used to separate and enrich Hg(II) selectively
      from eight metal ions with similar characteristics such as Cd(II), Ni(II),
      Co(II), Mn(II), Pb(II), Zn(II), Cu(II) and Fe(III). The pre-concentration factor
      is as high as 500. The results show that this new solid extractor has a good
      stability and can be reused for many times without decreasing its extraction
      percentage. The micro-column packed with diphenylcarbazone-functionalized silica
      gel was used for on-line solid-phase extraction and determination of mercury in
      real samples by flow-injection spectrophotometry. At the optimal conditions, the
      linear range and the detection limit for the determination of Hg(II) is found to
      be 1-1500 and 0.90 ng mL(-1), respectively. The relative standard deviation of 11
      replicate measurements is less than 3%. The proposed method was demonstrated to
      be simple, fast, selective, low cost and less pollution.

PMID- 17560021
TI  - The effect of various reaction parameters on bioremediation of perchlorate
      contaminated water.
AB  - The bioremediation was employed to treat perchlorate-contaminated water. All
      enrichments and growth of mixed cultures were performed in anaerobic acetate
      medium. Enrichment cultures were started with activated sludge obtained from a
      local wastewater treatment plant where it predominantly treats domestic
      wastewater. Several parameters affecting perchlorate removal were examined
      through batch experiments, these include the amount of domesticated sludge, the
      acetate concentration, pH, the C/N ratio and the reaction temperature. The
      results indicated that acetate was an effective carbon source and electron donor.
      Under the selected conditions, namely 1.0 g domesticated sludge, an acetate
      concentration of 1.2 g l(-1), pH 8.0, a C/N ratio of 20 at 40 degrees C, 50 mg l(
      1) perchlorate could be rapidly reduced to non-detectable levels within 24 h.

PMID- 17560022
TI  - Adsorption of copper and zinc from aqueous solutions by using natural clay.
AB  - In this study, removal of copper (Cu(2+)) and zinc (Zn(2+)) from aqueous
      solutions is investigated using Cankiri bentonite, a natural clay. During the
      removal process, batch technique is used, and the effects of pH, clay amount,
      heavy metal concentration and agitation time on adsorption efficiency are
      studied. Langmuir, Freundlich and Dubinin-Radushkevich (D-R) isotherms are
      applied in order to determine the efficiency of natural clay used as an
      adsorbent. Results show that all isotherms are linear. It is determined that
      adsorption of Cu(2+) and Zn(2+) is well-fitted by the second order reaction
      kinetic. In addition, calculated and experimental heavy metal amounts adsorbed by
      the unit clay mass are too close to each other. It is concluded that natural clay
      can be used as an effective adsorbent for removing Cu(2+) and Zn(2+) from aqueous
      solutions.

PMID- 17560023
TI  - Degradation of cyanobacteria toxin by advanced oxidation processes.
AB  - Advanced oxidation processes (AOPs) using O(3), H(2)O(2), O(3)/H(2)O(2),
      O(3)/Fe(II), and Fenton treatment were investigated for the degradation of
      aqueous solutions of cyanobacteria. The effects of concentration of reactants,
      temperature, and pH on toxins degradation were monitored and the reaction
      kinetics was assessed. O(3) alone or combined with either H(2)O(2) or Fe(II) were
      efficient treatment for toxins elimination. A higher toxin oxidation tendency was
      observed with Fenton reaction; total toxins degradation (MC-LR and MC-RR) was
      achieved in only 60s. The ozonation treatment was successfully described by
      second-order kinetics model, with a first-order with respect to the concentration
      of either ozone or toxin. At 20 degrees C, with initial concentration of MC-LR of
      1mg/L, the overall second-order reaction rate constant ranged from 6.79 x 10(4)
      to 3.49 x 10(3)M(-1)s(-1) as the solution pH increased from 2 to 11. The reaction
      kinetics of the other AOPs (O(3)/H(2)O(2), O(3)/Fe(II), and Fenton), were fitted
      to pseudo first-order kinetics. A rapid reaction was observed to took place at
      higher initial concentrations of O(3), H(2)O(2) and Fe(II), and higher
      temperatures. At pH 3, initial concentration of toxin of 1mg/L, the pseudo first
      order rate constant, achieved by Fenton process, was in order of 8.76+/-0.7s(-1).

PMID- 17560024
TI  - Application of the differential neural network observer to the kinetic parameters
      identification of the anthracene degradation in contaminated model soil.
AB  - In this work a new technique dealing with differential neural network observer
      (DNNO), which is related with differential neural networks (DNN) approach, is
      applied to estimate the anthracene dynamics decomposition and to identify the
      kinetic parameters in a contaminated model soil treatment by simple ozonation. To
      obtain the experimental data set, the model soil (sand) is combined with an
      initial anthracene concentration of 3.24mg/g and treated by ozone (with the ozone
      initial concentration 16mg/L) during 90min in a reactor by the "fluid bed"
      principle. The anthracene degradation degree was controlled by UV-vis
      spectrophotometry and HPLC techniques. Based on the HPLC data, the obtained
      results confirm that anthracene may be decomposed completely in the solid phase
      by simple ozonation during 20min and by-products of ozonation are started to be
      destroyed after 30min of treatment. In the ozonation process the ozone
      concentration in the gas phase at the reactor outlet is registered by an ozone
      detector. The variation of this parameter is used to obtain the summary
      characteristic curve of the anthracene ozonation (ozonogram). Then, using the
      experimental decomposition dynamics of anthracene and the ozonogram, the proposed
      DNNO is trained to reconstruct the anthracene decomposition and to estimate the
      anthracene ozonation constant using the DNN technique and a modified Least Square
      method.

PMID- 17560025
TI  - Correlation between the bond dissociation energies and impact sensitivities in
      nitramine and polynitro benzoate molecules with polynitro alkyl groupings.
AB  - The geometries of nine CHNO nitro-contained explosive molecules were fully
      optimized employing the B3LYP method of density functional theory with the 6-31G*
      basis set. The bond dissociation energy (BDE) for removal of the NO(2) group in
      nitroamine molecules with nitro alkyl, and benzoate with nitro alkyl were
      calculated at the same level. The calculational results of B3LYP/6-31G* and
      B3P86/6-311G* levels showed that the strength of C-NO(2) is weaker than that of N
      NO(2) bond in nitroamine molecules with nitro alkyl. The weakest bond is the C
      NO(2) in these computed molecules. The relationship between the impact
      sensitivities and the weakest C-NO(2) bond dissociation energy values was
      examined. The results indicate a nearly linear correlation between the impact
      sensitivity and the ratio of the BDE value to the molecular total energy.

PMID- 17560026
TI  - Toxicity of unwanted intermediates and products formed during accidental thermal
      decomposition of chemicals.
AB  - The problem of the formation of unwanted substances that can occur during thermal
      decomposition of chemicals is studied from a toxicological point of view. Two
      species, ethyl parathion (a widely used pesticide) and cumene hydroperoxide (an
      intermediate for the industrial production of phenol and acetone), are selected
      for this investigation. The hazards associated to their accidental thermal
      decomposition are estimated on the basis of the (known) intermediates and
      products formed by means of a computational tool (ECOSAR programme) and assessed
      experimentally by means of algal bioassays. Green alga Pseudokirchneriella is
      used as target organism for all the toxicological assessments. The results of
      these tests on the samples collected during the thermal decomposition of the two
      studied species indicate that in the case of ethyl parathion the decomposition
      process gives rise to a mixture of compounds which are more toxic than the parent
      species. On the other hand, the decomposition of cumene hydroperoxide in cumene
      results into the formation of different species whose toxicity towards the
      adopted organism is lower than that shown by the starting compound. A procedure
      is proposed to ascertain when it is necessary or it is avoidable to carry out
      further investigations that involve the analytical resolution of mixtures
      resulting from the thermal decomposition process. This approach is suggested as a
      preliminary screening to identify the hazards associated with an accidental
      decomposition either of pure chemicals or of mixtures of compounds.

PMID- 17560027
TI  - Removal of mercury species with dithiocarbamate-anchored polymer/organosmectite
      composites.
AB  - Mercury is one of the most toxic heavy metals found in solid and liquid waste
      disposed by chloro-alkali, paint, paper/pulp, battery, pharmaceutical, oil
      refinery and mining companies. Any form of mercury introduced to nature through
      any means is converted into a more toxic form such as methylmercury chloride (as
      produced by aquatic organisms) which usually accumulates in the tissue of fish
      and birds. The primary aim of this study was to investigate performance of
      dithiocarbamate-anchored polymer/organosmectite composites as sorbents for
      removal of mercury from aqueous solution. The modified smectite nanocomposites
      then were reacted with carbondisulfide to incorporate dithiocarbamate functional
      groups into the nanolayer of the organoclay. These dithiocarbamate-anchored
      composites were used for the removal of mercury species [Hg(II), CH(3)Hg(I) and
      C(6)H(5)Hg(I)]. Mercury adsorption was found to be dependent on the solution pH,
      mercury concentration and the type of mercury species to be adsorbed. The maximum
      adsorption capacities were equal to 157.3 mg g(-1) (782.5 micromol g(-1)) for
      Hg(II); 214.6 mg g(-1) (993.9 micromol g(-1)) for CH(3)Hg(I); 90.3 mg g(-1) (325
      micromol g(-1)) for C(6)H(5)Hg(I). The competitive adsorption capacities (i.e.
      adsorption capacities based on solutions containing all three mercuric ions) are
      7.7 mg g(-l) (38.3 micromol g(-1)), 9.2 mg g(-l) (42.6 micromol g(-1)) and 12.7
      mg g(-1) (45.7 micromol g(-1)) for Hg(II), CH(3)Hg(I) and C(6)H(5)Hg(I),
      respectively, at 10 ppm initial concentration. The adsorption capacities on molar
      basis were in order of C(6)H(5)Hg(I)>CH(3)Hg(I)>Hg(II).

PMID- 17560028
TI  - Differential regulation of glutamate receptors in trigeminal ganglia following
      masseter inflammation.
AB  - The present study examined whether N-methyl-D-aspartate receptor (NMDAR), 5-alpha
      amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) subunits and
      group I metabotropic glutamate receptors (mGluRs) are constitutively expressed in
      trigeminal ganglia (TG) using Western blot analysis in male Sprague-Dawley rats.
      We then investigated whether experimental induction of masseter inflammation
      influences glutamate receptor expressions by comparing the protein levels from
      naive rats to those from complete Freund's adjuvant (CFA) inflamed rats. Our
      results showed that NMDAR1 (NR1), NMDAR2A (NR2A), NMDAR2B (NR2B), AMPAR1 (GluR1)
      and AMPAR2 (GluR2) subunits, and group I metabotropic glutamate receptor, mGluR5,
      are constitutively expressed in TG. Masseter inflammation significantly down
      regulated NR1 subunit expression that persisted to 7 days post-CFA inflammation.
      NR2A and NR2B expressions were not significantly changed. GluR1 receptor subunit
      expression was slightly increased in TG 3 days after CFA-induced inflammation,
      but the change was not statistically significant. GluR2 protein level was not
      affected by CFA inflammation. The level of mGluR5 protein was significantly up
      regulated in TG 3 days after CFA-induced masseter inflammation. There were no
      inflammation-induced changes in any of the proteins we analyzed in the
      contralateral, non-inflamed TG. These results suggested that muscle inflammation
      differentially modulates glutamate receptor subunits at the primary afferent
      level in male rats and that these inflammation-induced transcriptional changes
      may contribute to functionally different aspects of craniofacial muscle pain.

PMID- 17560029
TI  - Variable-force tapping atomic force microscopy as a tool in the characterization
      of organic devices.
AB  - A common method for characterizing the phase separation of materials in mixtures
      is tapping mode atomic force microscopy (AFM). However, AFM results are
      influenced by surface-energy effects and the employed tapping force, and it might
      therefore be difficult to attain correct information regarding the bulk with such
      a surface-imaging technique. In this work, we present a way of imaging material
      phase separation in an improved manner by recording a series of AFM images at
      different tapping force. More specifically, we have employed the variable-force
      AFM method on organic mixtures, comprising a conjugated polymer (MEH-PPV) and an
      ion-conducting polymer electrolyte (PEO-XCF(3)SO(3), X=Li, K, Rb), and we
      demonstrate that it is capable of reversibly sampling such materials not only on
      the surface, but also (indirectly) in the topmost part of the bulk. The analysis
      of the evolution of AFM phase images allows us to (indirectly) gain information
      about the bulk-phase separation of materials. We find that the variable-force AFM
      results correlate well with the device performance of light-emitting
      electrochemical cells employing such organic mixtures as the active material.

PMID- 17560030
TI  - Exploring the molecular forces within and between CbsA S-layer proteins using
      single molecule force spectroscopy.
AB  - We used single molecule atomic force microscopy (AFM) to gain insight into the
      molecular forces driving the folding and assembly of the S-layer protein CbsA.
      Force curves recorded between tips and supports modified with CbsA proteins
      showed sawtooth patterns with multiple force peaks of 58+/-26pN that we attribute
      to the unfolding of alpha-helices, in agreement with earlier secondary structure
      predictions. The average unfolding force increased with the pulling speed but was
      independent on the interaction time. Force curves obtained for CbsA peptides
      truncated in their C-terminal region showed similar periodic features, except
      that fewer force peaks were seen. Furthermore, the average unfolding force was
      83+/-45pN, suggesting the domains were more stable. By contrast, cationic
      peptides truncated in their N-terminal region showed single force peaks of 366+/
      149pN, presumably reflecting intermolecular electrostatic bridges rather than
      unfolding events. Interestingly, these large intermolecular forces increased not
      only with pulling speed but also with interaction time. We expect that the intra-
      and intermolecular forces measured here may play a significant role in
      controlling the stability and assembly of the CbsA protein.

PMID- 17560031
TI  - Investigation of hole states near the Fermi level in Nb(1-)(x)Mg(x)B(2) by
      electron energy-loss spectroscopy and first-principles calculations.
AB  - The fine structures of the electron energy-loss spectra (EELS) for the B-K edge
      have been examined in NbB(2) and superconducting Nb(0.75)Mg(0.25)B(2). The
      experimental results are analyzed based on the calculations of density functional
      theory (DFT) using the Wien2k code. The results of the EELS spectra and the
      angular decomposition of the density of states (DOS) reveal that both the B p(z)
      and B p(x)+p(y) states in NbB(2) have large weights at the Fermi energy due to
      intersheet covalent bonding with notable hybridization between the Nb 4d and B 2p
      states. This kind of hybridization also results in different core-hole behaviors
      for the B-K edge in two orthogonal crystallographic orientations. The best fit
      between experimental and theoretical data is achieved with consideration of the
      core-hole effect of the B 1s states, in particular for the q perpendicular c
      spectra. Analysis of the electronic structure of the Nb(1-)(x)Mg(x)B(2)
      superconductors suggests that confinement of the intersheet covalent bonding is
      likely to be favorable for the improvement of superconductivity in this kind of
      materials.

PMID- 17560032
TI  - Force-clamp spectroscopy with a small dithering of AFM tip, and its application
      to explore the energy landscape of single avidin-biotin complex.
AB  - We have recently developed a new method for directly measuring the spring
      constant of single molecules and molecular complexes on a real-time basis [L.A.
      Chtcheglova, G.T. Shubeita, S.K. Sekatskii, G. Dietler, Biophys. J. 86 (2004)
      1177]. The technique combines standard force spectroscopy with a small dithering
      of tip. Changes in the amplitude of the oscillations are measured as a function
      of the pulling-off force to yield the spring constant of the complex. In this
      report, we present the first results of combination of this approach with the
      force-clamp spectroscopy. The standard atomic-force microscope has been
      supplemented with an electronic unit, which is capable of realizing an arbitrary
      force function, and permits the force-loading regime to be interrupted at any
      time. Using this method, the time needed to rupture a single bond can be measured
      as a function of the force that is required to maintain the complex in a
      stretched condition. The energy landscape of the avidin-biotin complex is
      explored and discussed.

PMID- 17560033
TI  - Comparison of different aminofunctionalization strategies for attachment of
      single antibodies to AFM cantilevers.
AB  - Atomic force microscopy (AFM) has developed into a key technique for elucidation
      of biological systems on the single molecular level. In particular, molecular
      recognition force microscopy has proven to be a powerful tool for the
      investigation of biological interactions under near physiological conditions. For
      this purpose, ligands are tethered to AFM tips and the interaction forces with
      cognate receptors on the sample surface are measured with pico-Newton accuracy.
      In the first step of tip functionalization, amino groups are typically introduced
      on the initially inert AFM tip. Several methods have been developed to
      reproducibly adjust the desired low density of amino groups on the tip surface,
      i.e. esterification with ethanolamine, gas-phase silanization with aminopropyl
      triethoxysilane (APTES), or treatment with aminophenyl-trimethoxysilane (APhS) in
      toluene solution. In the present study, the usefulness of these methods for
      attachments of antibodies to AFM tips was characterized by a standardized test
      system, in which biotinylated IgG was bound to the tip and a dense monolayer of
      avidin on mica served as test sample. All three methods of aminofunctionalization
      were found fully satisfactory for attachment of single antibodies to AFM tips,
      only in a parallel macroscopic assay on silicon nitride chips a minor difference
      was found in that APTES appeared to yield a slightly lower surface density of
      amino groups.

PMID- 17560034
TI  - Parasitic nematodes - from genomes to control.
AB  - The diseases caused by parasitic nematodes in domestic and companion animals are
      major factors that decrease production and quality of the agricultural products.
      Methods available for the control of the parasitic nematode infections are mainly
      based on chemical treatment, non-chemical management practices, immune modulation
      and biological control. However, even with integrated pest management that
      frequently combines these approaches, the effective and long-lasting control
      strategies are hampered by the persistent exposure of host animals to
      environmental stages of parasites, the incomplete protective response of the host
      and acquisition of anthelmintic resistance by an increasing number of parasitic
      nematodes. Therefore, the challenges to improve control of parasitic nematode
      infections are multi-fold and no single category of information will meet them
      all. However, new information, such as nematode genomics, functional genomics and
      proteomics, can strengthen basic and applied biological research aimed to develop
      improvements. In this review we will, summarize existing control strategies of
      nematode infections and discuss ongoing developments in nematode genomics.
      Genomics approaches offer a growing and fundamental base of information, which
      when coupled with downstream functional genomics and proteomics can accelerate
      progress towards developing more efficient and sustainable control programs.

PMID- 17560035
TI  - African trypanosomosis: from immune escape and immunopathology to immune
      intervention.
AB  - African trypanosomes can cause prolonged chronic infections through a mechanism
      of antigen variation whereby they manipulate the humoral immune system of their
      hosts. However, besides antigenic variation these extracellular parasites exert
      other immunoregulatory activities mainly mediated by innate cells in particular
      macrophage-like (M) cells. In this review, the modulation of M cells through
      parasite factors and host cytokines as well as their role in parasite control and
      immunopathology will be examined. The concept of M cell polarization into
      distinct activation states (M1, M2) that may contribute to trypanosusceptibility
      or resistance will be discussed. Finally, the possibility to interfere with such
      activation states hereby providing new therapeutical modalities in the treatment
      of this infectious disease will be illustrated.

PMID- 17560036
TI  - Calcium ionophore-induced egress of Toxoplasma gondii shortly after host cell
      invasion.
AB  - Calcium plays crucial roles in important events of Toxoplasma gondii life cycle,
      including motility, invasion and egress from the host cell. Calcium ionophore has
      been used to artificially trigger release of the parasites from infected cells.
      In this report we describe that calcium ionophore A21387 induced T. gondii egress
      from LLC-MK2 cells at times as early as 2 h after entry. Addition of kinase
      inhibitors as staurosporine, wortmanine and genistein to the incubation medium
      significantly reduced ionophore-induced egress. The same occurred when the actin
      inhibitor cytochalasin D was used. Parasites egressed 2 h post-infection from
      ionophore-treated cultures were unable of establishing infection in a new cell. S
      VHS recording of egressing parasites showed that they assume an hourglass shape
      as they cross the plasma membrane, similar to the moving junction constriction
      observed during active invasion, and extrudes the conoid, similarly to what is
      also observed during invasion. Transmission and high resolution scanning electron
      microscopy revealed that the egressing tachyzoites are free from host cell
      derived membranes. These include plasma membrane and parasitophorous vacuole
      membranes as well as associated endoplasmic reticulum membranes. Taken together,
      these results indicate that although invasion and egress may share similar
      signaling pathways, as indicated by the effect of kinase and actin inhibitors,
      the tachyzoites move freely in the cytosol, a phenomenon very distinctive from
      invasion and that deserves attention.

PMID- 17560037
TI  - Detection and biochemical characterisation of a novel polymorphism in the human
      GSTP1 gene.
AB  - The glutathione transferases (GSTs) mediate the detoxification of a broad
      spectrum of electrophilic chemicals. We report here the identification and
      characterisation of a novel naturally occurring transition that changes codon 169
      from GGC (Gly) to GAC (Asp) in the human Pi class GST, GSTP1. Expression of the
      variant in human HepG2 cells led to a small increase in 1-chloro-2,4
      dinitrobenzene (CDNB) conjugation compared to the wild-type protein. Asp(169)
      GSTP1-1 expressed at high levels in Escherichia coli displayed a small but
      significant increase in specific activity towards CDNB compared to Gly(169) GSTP1
      1. The catalytic efficiency with CDNB was higher for Asp(169) GSTP1-1 compared to
      the wild-type enzyme, although the kinetic constants of the mutant and the wild
      type enzyme towards glutathione were not different. Modelling indicated that the
      mutation does not appear to change protein conformation. The distribution of the
      genotypes in a normal healthy population (217 individuals) was 94.3% for the
      Gly/Gly genotype and 5.7% for the Gly/Asp genotype; no Asp/Asp genotypes were
      detected in this population. The frequency of the Asp(169) allele in the only
      oxidative stress-linked pathology that we have studied to date, i.e. alcoholic
      liver disease, was not significantly different from healthy controls. In
      conclusion, we have detected and characterised a novel SNP in GSTP1 that may play
      a role in modulating the activity of GSTP1-1.

PMID- 17560038
TI  - Self-complementary sequences induce the formation of double-stranded filamentous
      phages.
AB  - The single strand nature of the filamentous phage (Ff) genome is currently one of
      the main drawbacks for their application as gene delivery vectors. In this work,
      by the incorporation of inverted self complementary sequences into the genome of
      Ff, we were able to convert single strand genome of Ff into double strand DNA
      structures. The presence of self complementary sequences in phage genome did not
      affect viral yields significantly, and the formation of double strands structures
      was successfully determined by a Mung Bean Nuclease resistance assay. Upon
      transfection into HEK293 cells, the double strand DNA structures showed to be
      readable by the transcriptional machinery of mammalian cells.

PMID- 17560039
TI  - Long-term effects of nicotine on rat fungiform taste buds.
AB  - Nicotine, an alkaloid found in tobacco smoke, has been recognized as capable of
      inducing changes in taste functionality in conditions of chronic exposure. The
      mechanisms underlying these sensory alterations, however, are currently unknown.
      We addressed this issue by studying the long-term effects of nicotine on the
      anatomical features of taste buds, the peripheral end-organs of taste, in rat
      fungiform papillae. Nicotine was administered to rats via drinking water over a
      period of 3 weeks, which represents a standard method to achieve chronic drug
      exposure in laboratory animals. We found that prolonged administration of
      nicotine induced a significant reduction in the size of fungiform taste buds,
      without affecting their total number on the rat tongue. Morphometric measurements
      as well as evaluations of taste cell membrane capacitance suggested that the
      reduced size of taste organs was determined by a decrease in the number of cells
      per taste bud. In addition, chronic treatment with nicotine caused an increase in
      the relative density of cells expressing gustducin, a specific G protein alpha
      subunit found in some taste cells and involved in bitter/sweet transduction.
      Interestingly, changes in the expression pattern of gustducin turned out to be
      more pronounced in periadolescent/adolescent than in adult rats. As a whole, our
      data indicate that long-term nicotine administration induces significant changes
      in the anatomical properties of taste buds in rat fungiform papillae. These
      changes could have a profound impact on the sensory information relayed to the
      brain; therefore, they may be responsible, at least in part, for the alterations
      in taste functionality observed during chronic nicotine exposure, a condition
      found in regular smokers.

PMID- 17560040
TI  - Inflammation and dephosphorylation of the tight junction protein occludin in an
      experimental model of multiple sclerosis.
AB  - Multiple sclerosis (MS) is a disease of the CNS in which inflammation,
      demyelination and neurodegeneration contribute to its initiation and progression.
      A frequently employed model of MS is experimental autoimmune encephalomyelitis
      (EAE). Here, to gain new insights into the disease process, an analysis of
      proteins in extracts of lumbar spinal cord from naive and EAE rats was
      undertaken. The data mainly confirm that inflammation and blood-brain barrier
      (BBB) breakdown are the major hallmarks of disease in this model. Given their
      importance in the BBB, junctional proteins were further investigated. Occludin, a
      protein localizing to tight junctions in brain endothelial cells, showed
      strikingly increased migration in EAE when analyzed by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis (SDS-PAGE). This increased migration was
      mimicked by in vitro phosphatase treatment, implying its dephosphorylation in
      EAE. Occludin dephosphorylation coincided with the onset of inflammation,
      slightly preceding visible signs of disease, and was just prior to apparent
      changes in BBB permeability. These findings suggest occludin is a target for
      signaling processes in EAE, perhaps regulating the response of the BBB to the
      inflammatory environment as seen in MS.

PMID- 17560041
TI  - Acute onset by 5-HT(6)-receptor activation on rat brain brain-derived
      neurotrophic factor and activity-regulated cytoskeletal-associated protein mRNA
      expression.
AB  - A number of previous studies have shown that chronic but not acute treatment with
      antidepressant drugs targeting the central 5-HT system, enhances mRNA expression
      for a number of genes including, brain-derived neurotrophic factor (BDNF) and the
      effector immediate early gene (IEG), activity-regulated, cytoskeletal-associated
      protein (Arc). The present study investigated the effects of 5-HT(6)-receptor
      activation on hippocampal and cortical levels of mRNA expression of BDNF and Arc
      in the rat. The selective 5-HT(6)-receptor agonist LY-586713 was administered
      acutely (0.1-10 mg/kg, s.c.) and mRNA levels of BDNF and Arc were measured 18 h
      later. Administration of LY-586713 caused a bell-shaped dose response on
      hippocampal BDNF mRNA expression, having no effect at 0.1 mg/kg, a significant up
      regulation at 1 mg/kg and no effect at 10 mg/kg. The up-regulation in BDNF
      expression observed at 1 mg/kg was completely blocked by pre-treatment with the
      selective 5-HT(6)-receptor antagonist SB-271046 (10 mg/kg, s.c.). The effective
      dose (1 mg/kg) of LY-586713 on the induction of BDNF expression was also tested
      on Arc expression. Acute administration of LY-586713 at this dose caused marked
      increases of the Arc mRNA levels in cortical and hippocampal regions. These
      increases were also attenuated by SB-271046 (10 mg/kg) in all regions of the
      hippocampus, as well as the parietal cortex. However, in frontal cortical regions
      there was no attenuation by the antagonist. Moreover, SB-271046 alone increased
      Arc expression in these regions. The results presented here provide the first
      evidence for the involvement of the 5-HT(6) receptor in regulating BDNF and Arc
      mRNA expression, suggesting that LY-586713 has potential effects on neuronal
      plasticity. Overall, these findings suggest that, as opposed to more general 5-HT
      receptor activation by, for example, antidepressants, direct 5-HT(6)-receptor
      activation results in a more rapid rise in BDNF and Arc mRNA expression which
      does not require repeated administration.

PMID- 17560042
TI  - Dexamethasone transiently attenuates up-regulation of endostatin/collagen XVIII
      following traumatic brain injury.
AB  - Endostatin/collagen XVIII is a specific inhibitor of endothelial proliferation
      and migration in vitro. It has also been shown to have anti-angiogenic activity
      and tumor growth inhibitory activity in vivo and in vitro. Here we studied
      expression of endostatin/collagen XVIII in a rat traumatic brain injury (TBI)
      model, focusing on the early phase. A significant up-regulation of
      endostatin/collagen XVIII in TBI began as early as 24 h post-TBI. Double-staining
      experiment revealed that the major resource of endostatin/collagen XVIII(+) cells
      in our TBI rat model was a subpopulation of reactivated microglia/macrophages.
      Our data further showed that dexamethasone attenuated up-regulation of
      endostatin/collagen XVIII expression at days 1 and 2, but not at day 4, post-TBI,
      indicating that dexamethasone might possess an early and transient influence to
      the angiogenesis following TBI.

PMID- 17560043
TI  - Soluble amyloid beta1-42 reduces dopamine levels in rat prefrontal cortex:
      relationship to nitric oxide.
AB  - Several studies suggest a pivotal role of amyloid beta (Abeta)(1-42) and nitric
      oxide (NO) in the pathogenesis of Alzheimer's disease. NO also possess central
      neuromodulatory properties. To study the soluble Abeta(1-42) effects on dopamine
      concentrations in rat prefrontal cortex, microdialysis technique was used. We
      showed that i.c.v. injection or retrodialysis Abeta(1-42) administration reduced
      basal and K(+)-stimulated dopamine levels, measured 2 and 48 h after peptide
      administration. Immunofluorescent experiments revealed that after 48 h from
      i.c.v. injection Abeta(1-42) was no longer detectable in the ventricular space.
      We then evaluated the role of NO on Abeta(1-42)-induced reduction in dopamine
      concentrations. Subchronic L-arginine administration decreased basal dopamine
      levels, measured either 2 h after i.c.v. Abeta(1-42) or on day 2 post-injection,
      whereas subchronic 7-nitroindazole administration increased basal dopamine
      concentrations, measured 2 h after i.c.v. Abeta(1-42) injection, and decreased
      them when measured on day 2 post-Abeta(1-42)-injection. No dopaminergic response
      activity was observed after K(+) stimulation in all groups. These results suggest
      that the dopaminergic system seems to be acutely vulnerable to soluble Abeta(1
      42) effects. Finally, the opposite role of NO occurring at different phases might
      be regarded as a possible link between Abeta(1-42)-induced effects and
      dopaminergic dysfunction.

PMID- 17560044
TI  - Elevations of FosB in the nucleus accumbens during forced cocaine abstinence
      correlate with divergent changes in reward function.
AB  - Dysregulation of hedonic processing, in which seeking of drug reward becomes more
      desirable than seeking natural rewards, like food, sex, and novelty, is a
      consequence of chronic drug exposure and potentially leads to escalating drug
      usage and addiction. Here, we investigated the effects of chronic cocaine
      treatment (10 days of escalating doses of cocaine, 10-30 mg/kg) and multiple
      forced abstinence periods (2, 3 or 5 weeks) on the acute rewarding properties of
      either cocaine (10 mg/kg) or novel-objects using the conditioned place preference
      procedure. Following all cocaine withdrawal periods, cocaine preference was
      significantly elevated while novel object preference was abolished compared with
      saline-treated rats. At the earliest withdrawal period, these behavioral changes
      were accompanied by elevations in FosB-like immunoreactive staining in the
      basolateral amygdala (BLA) and nucleus accumbens shell (NAc-Sh) and core (NAc-C).
      FosB staining in all three brain areas correlated positively with cocaine
      preference, but negatively with novelty preference. After 5 weeks of withdrawal,
      FosB staining was only elevated in the NAc-Sh and again correlated positively
      with elevated cocaine preference but negatively with decreased novelty
      preference. These data indicate that alterations in the expression of FosB-like
      transcription factors in the NAc can predict the dysregulation of hedonic
      processing that occurs during protracted withdrawal from cocaine.

PMID- 17560045
TI  - Cortical oscillatory changes during warming and heating in humans.
AB  - Warmth and heat are registered by different types of cutaneous receptors. To
      disentangle the cortical activation patterns of warming and heating, we analyzed
      the temporal evolution of the electroencephalographic 10 and 20 Hz oscillations
      with the time resolution of hundreds of milliseconds. Sixty heat (from 32 to 50.5
      degrees C, rate of change 6 degrees C/s) and warm (from 32 to 42 degrees C, 6
      degrees C/s) stimuli were applied on the right thenar using contact thermode. EEG
      was recorded from 111 scalp electrodes in 12 healthy subjects, and analyzed using
      event-related desynchronization and low-resolution electromagnetic tomography
      methods. During warming, the amplitudes of 10 and 20 Hz oscillations over the
      contralateral primary sensorimotor (SI/MI) and premotor cortices decreased, and
      the amplitude of 20 Hz oscillations in the anterior cingulate and ipsilateral
      premotor cortex increased. Heating was associated with additional profound
      amplitude decreases of 10 and 20 Hz oscillations over SI/MI and premotor cortex,
      and by amplitude increase of 20 Hz oscillations originating in the posterior
      cingulate cortex. Results suggest biphasic amplitude changes of the cortical
      oscillations during ramp increase of temperature attributable to the periods of
      warming and heating. The amplitude decreases of 10 and 20 Hz oscillations in
      SI/MI and premotor cortex possibly aid in preparation of motor withdrawal
      reaction in an event that temperature should reach intolerable pain.
      Synchronization of the 20 Hz oscillations in the anterior and especially in the
      posterior cingulate cortex may aid suppression of unwanted movements.

PMID- 17560046
TI  - Neural remodeling may partly contribute to the abnormality of excitation
      contraction coupling in heart failure.
AB  - Heart failure (HF) is a major and growing public health problem in the world.
      About 50% of deaths in HF occur suddenly due to malignant arrhythmia. Therefore,
      exploring the further mechanisms of chronic HF and finding new therapy targets
      are essential for the progression of HF treatment. Recently, some published
      papers suggested that myocardial neural remodeling and abnormal excitation
      contraction (EC) coupling might partly contribute to the development of HF and
      sudden cardiac death. Even though a few studies have demonstrated that the
      sympathetic nerve system (SNS) may have significant impact on the functional
      states of myocardial EC coupling through the beta-adrenergic signaling pathway,
      so far, it still remains unknown that whether neural remodeling affects the EC
      coupling. Studies from Marks' group demonstrated that 70% of cardiac ryanodine
      receptors (RyR2), which located on the sarcoplasmic reculum (SR) controlling
      intracellular Ca(2+) release and muscle contraction in the heart, from failing
      hearts were abnormal and only 15% exhibited the most severe defects. In addition,
      Litwin et al. observed that temporal and spatial heterogeneities in local Ca(2+)
      release events in a rabbit model of HF after myocardial infarction. Because some
      studies have demonstrated that chronic SNS hyperactivity in HF led to protein
      kinase A (PKA) hyperphosphorylation of RyR2 in the heart, and the myocardial
      sympathetic nerve distribution become heterogeneous in the setting of HF. Thus,
      it is reasonable for us to propose the hypothesis that neural remodeling may
      partly account for the abnormality of EC coupling in HF.

PMID- 17560047
TI  - Cancer is a disease of unregulated expansion of somatic stem cells resulting from
      disrupted asymmetric division.

PMID- 17560048
TI  - Periodontal ligament cells from redundant teeth are supposed to be resources for
      stem-cell-mediated periodontal regeneration.

PMID- 17560049
TI  - Does autoimmunity of endogenous vasoactive neuropeptides cause retinopathy in
      humans?
AB  - Immune privilege is a physiologic mechanism within the eye which protects it
      against pathogens, while also protecting it from inflammation. Immunological
      mechanisms in the eye must be tightly regulated to ensure externally mediated
      injury and infection or internally mediated autoimmunity do not exceed self
      defence tolerance. Vasoactive neuropeptides (VNs) including vasoactive intestinal
      peptide (VIP) and pituitary adenylate cyclase polypeptide (PACAP) and their
      receptors exist in the mammalian eye including the sclera, cornea, iris, ciliary
      body, ciliary process and the retina and may have a role in protecting these
      normally immune privileged sites. VN receptors are class II G protein-coupled
      receptors (GPCRs) which couple primarily to the adenylate cyclase (AC)-cyclic AMP
      pathway. A sound blood supply is essential for retinal survival hence vascular
      compromise will have serious consequences. Retinal vasculitis is a potentially
      blinding condition with a strong association with systemic inflammatory diseases.
      Compromise of the endothelial barriers and the blood retina barrier (BRB) may
      instigate inflammatory responses setting up a chain of events involving VNs in a
      manner which provokes autoimmunity to them. Protection from BRB breakdown may be
      linked to nitric oxide (NO) effects and actions of phosphodiesterase inhibitors
      and cAMP production. Induced NO expressed under influences of inflammatory
      mediators evokes neurodegeneration and cell apoptosis and may lead to serious
      ocular disease including retinal injury. Other inflammatory mediators also play a
      role in retinal pathology. PACAP and glutamate are co-stored in the
      retinohypothalamic tract and PACAP attenuates glutamate induced neurotoxicity in
      cultured retinal neurons suggesting that compromise of this VN would have
      significant detrimental impact on retinal viability though glutamate toxicity.
      Additional effects of VN compromise would possibly occur through unopposed
      vasoconstriction and inflammation. Proof of this hypothesis has important
      implications for treatment and prevention of autoimmune retinopathy and blindness
      as a number of therapeutic pathways may be opened. Importantly for therapeutic
      contexts cAMP effects are maintained by phosphodiesterase (PDE) inhibitors which
      could be used in VN autoimmune disorders. A compelling case may exist to
      undertake a therapeutic trial of VN replacement, PDE inhibitors and other agents
      in autoimmune retinopathies resulting from possible VN autoimmunity.

PMID- 17560050
TI  - Long-term outcomes after radiotherapy for retroperitoneal and deep truncal
      sarcoma.
AB  - PURPOSE: To determine the long-term outcomes after multimodality treatment of
      retroperitoneal, pelvic, and deep truncal sarcomas and to identify the factors
      associated with local control (LC), distant metastasis (DM), and overall survival
      (OS). METHODS AND MATERIALS: A total of 85 patients with retroperitoneal, pelvic,
      and deep truncal sarcomas were treated with radiotherapy (RT) between 1987 and
      2005. A retrospective analysis of LC, DM, and OS was conducted using log-rank and
      Cox regression statistical methods. RESULTS: The 2- and 5-year LC, DM, and OS
      rates were 66% and 51%, 38% and 58%, and 70% and 34%, respectively. Negative
      surgical margins and a higher radiation dose were associated with greater LC
      rates on both univariate and multivariate analyses, and female gender was
      significantly associated with greater LC on multivariate analysis only. None of
      the analyzed risk factors was significantly associated with DM, although patients
      with high-grade tumors showed a trend toward an increased risk of DM. Gross
      residual disease after resection and high tumor grade were associated with worse
      OS rates on univariate and multivariate analyses, and male gender was
      significantly associated with worse OS on multivariate analysis only. A time
      dependent analysis of LC in relation to DM demonstrated that patients with local
      failure had a hazard ratio of 19.7 for DM compared with patients without local
      failure (p < 0.0001). Of the 85 patients, 5 and 8, respectively, had clinically
      significant acute and late toxicity. CONCLUSION: The results of this study
      emphasize the importance of LC in patients with retroperitoneal sarcoma.
      Radiation dose escalation or radiosensitization strategies to enhance LC are
      warranted.

PMID- 17560051
TI  - Intensity-modulated radiotherapy of head and neck cancer aiming to reduce
      dysphagia: early dose-effect relationships for the swallowing structures.
AB  - PURPOSE: To present initial results of a clinical trial of intensity-modulated
      radiotherapy (IMRT) aiming to spare the swallowing structures whose dysfunction
      after chemoradiation is a likely cause of dysphagia and aspiration, without
      compromising target doses. METHODS AND MATERIALS: This was a prospective,
      longitudinal study of 36 patients with Stage III-IV oropharyngeal (31) or
      nasopharyngeal (5) cancer. Definitive chemo-IMRT spared salivary glands and
      swallowing structures: pharyngeal constrictors (PC), glottic and supraglottic
      larynx (GSL), and esophagus. Lateral but not medial retropharyngeal nodes were
      considered at risk. Dysphagia endpoints included objective swallowing dysfunction
      (videofluoroscopy), and both patient-reported and observer-rated scores.
      Correlations between doses and changes in these endpoints from pre-therapy to 3
      months after therapy were assessed. RESULTS: Significant correlations were
      observed between videofluoroscopy-based aspirations and the mean doses to the PC
      and GSL, as well as the partial volumes of these structures receiving 50-65 Gy;
      the highest correlations were associated with doses to the superior PC (p =
      0.005). All patients with aspirations received mean PC doses >60 Gy or PC V(65)
      >50%, and GSL V(50) >50%. Reduced laryngeal elevation and epiglottic inversion
      were correlated with mean PC and GSL doses (p < 0.01). All 3 patients with
      strictures had PC V(70) >50%. Worsening patient-reported liquid swallowing was
      correlated with mean PC (p = 0.05) and esophageal (p = 0.02) doses. Only mean PC
      doses were correlated with worsening patient-reported solid swallowing (p = 0.04)
      and observer-rated swallowing scores (p = 0.04). CONCLUSIONS: These dose-volume
      effect relationships provide initial IMRT optimization goals and motivate further
      efforts to reduce swallowing structures doses to reduce dysphagia and aspiration.

PMID- 17560053
TI  - Isolation and characterization of nine bacteriophages that lyse O149
      enterotoxigenic Escherichia coli.
AB  - The goal of this study was to isolate and characterize phages that might be used
      in prevention and treatment of porcine post-weaning diarrhea due to O149
      enterotoxigenic E. coli (ETEC). Serotype O149:H10:F4 was especially targeted
      because this is the dominant ETEC serotype. Mixtures of 10 strains of O149:H10:F4
      ETEC and of 10 O149:H43:F4 ETEC were used as hosts for isolation of phages in
      sewage from 38 Ontario pig farms. Six phages (GJ1-GJ6) that lysed O149:H10:F4
      ETEC and three (GJ7-GJ9) that lysed O149:H43:F4 ETEC were isolated. All phages
      produced large, clear plaques. All nine phages had necks and contractile tails
      and therefore belonged to the Myoviridae. Their estimated genome sizes were 48.3
      50.7kb and their restriction enzyme fragments suggested that they were closely
      related. Phages GJ1-GJ6 lysed 99-100% of 85 O149:H10:F4 ETEC, 0-12% of 42
      O149:H43:F4 ETEC, 3-35% of 37 non-O149 porcine ETEC, and 6-68% of the 72 strains
      of the ECOR collection. Phages GJ7-GJ9 lysed 86-98% of the O149:H43:F4 ETEC, 2
      53% of the O149:H10:F4 ETEC, and 24-41% of the non-O149 porcine ETEC. Titres of
      the nine phages were unaffected by exposure for 16h to pH 5-9. Among phages GJ1
      GJ6, resistance of O149:H10:F4 ETEC to one phage was generally not accompanied by
      resistance to other phages. It is concluded that the nine phages are suitable
      candidates for prophylaxis and therapy of porcine post-weaning diarrhea due to
      O149 ETEC.

PMID- 17560052
TI  - High expression of tumor endothelial marker 7 is associated with metastasis and
      poor survival of patients with osteogenic sarcoma.
AB  - Our objective is to identify genes regulating metastasis of osteogenic sarcoma
      (OGS) since metastasis is the primary cause of mortality among patients with OGS.
      To identify such genes, we first created a database of differentially expressed
      genes between six low-grade and six high-grade OGS tumors, and between a normal
      immortalized osteoblast cell line (FOB) and four commercially available OGS
      derived cell lines. We specifically searched for surface proteins over-expressed
      in high-grade OGS, since we hypothesize that tumor-cell specific surface markers
      are key to metastasis. A gene encoding Tumor Endothelial Marker7 (TEM7) was
      selected as a candidate for further study. TEM7 expression pattern was assessed
      by RT-PCR, Western blotting and immunostaining. TEM7 mRNA was abundantly
      expressed in SAOS cells (derived from high-grade OGS), but not in FOB or MG63
      cells (derived from low-grade OGS). Virtually no expression of TEM7 protein was
      observed in FOB cells but abundant expression was noted in SAOS and TE85 cells.
      Employing immunostaining of 92 human OGS specimens (50 high-grade and 42 low
      grade) collected before chemotherapy show 97% (37 of 38) of high-grade OGS
      specimens with metastasis have high TEM7 staining. Further, we found that
      elevated expression of TEM7 correlated with poor survival (p<0.04) of affected
      patients. Inhibiting TEM7 function by siRNA inhibited invasion and migration of
      OGS cells with metastatic potential. Our results suggest TEM7 expression level
      closely parallels histology-based prognostication of OGS metastasis and,
      therefore, it is a therapeutic target. This is the first demonstration of a link
      between TEM7 and cancer metastasis.

PMID- 17560054
TI  - A peptide derived from human bactericidal/permeability-increasing protein (BPI)
      exerts bactericidal activity against Gram-negative bacterial isolates obtained
      from clinical cases of bovine mastitis.
AB  - Gram-negative bacteria are responsible for approximately one-third of the
      clinical cases of bovine mastitis and can elicit a life-threatening, systemic
      inflammatory response. Lipopolysaccharide (LPS) is a membrane component of Gram
      negative bacteria and is largely responsible for evoking the inflammatory
      response. Antibiotic and anti-inflammatory therapy for treating Gram-negative
      infections remains suboptimal. Bactericidal/permeability-increasing protein (BPI)
      is a neutrophil-derived protein with antimicrobial and LPS-neutralizing
      properties. Select peptide derivatives of BPI are reported to retain these
      properties. The objective of this study was to evaluate the antimicrobial
      activity of a human BPI-derived synthetic peptide against clinical bovine
      mastitis isolates of Gram-negative bacteria. A hybrid peptide was synthesized
      corresponding to two regions of human BPI (amino acids 90-99 and 148-161), the
      former of which has bactericidal activity and the latter of which has LPS
      neutralizing activity. The minimum inhibitory (MIC) and bactericidal (MBC)
      concentrations of this peptide against various genera of bacteria were determined
      using a broth microdilution assay. The MIC's were determined to be: 16-64
      microg/ml against Escherichia coli; 32-128 microg/ml against Klebsiella
      pneumoniae and Enterobacter spp.; and 64-256 microg/ml against Pseudomonas
      aeruginosa. The MBC's were equivalent to or 1-fold greater than corresponding
      MIC's. The peptide had no growth inhibitory effect on Serratia marcescens. The
      antimicrobial activity of the peptide was retained in the presence of serum, but
      severely impaired in milk. Further functional evaluation of the peptide
      demonstrated its ability to completely neutralize LPS. Together, these data
      support additional investigations into the therapeutic application of BPI to the
      treatment of Gram-negative infections in cattle.

PMID- 17560055
TI  - Nanosizing of a drug/carrageenan complex to increase solubility and dissolution
      rate.
AB  - In this study, we present a novel approach of nanosizing a drug/polymeric complex
      to increase both solubility and dissolution rate of poorly water-soluble
      compounds. A hydrophilic polymer, lambda-carrageenan, was first complexed with a
      model poorly water-soluble compound to increase the compound's aqueous
      solubility. The compound/carrageenan complex was further nanosized by wet-milling
      to enhance the dissolution rate. By complexing with carrageenan, the compound
      became amorphous in the complex. Using additional carrageenan as a stabilizer for
      nanosizing, a nanosuspension of a compound/carrageenan complex with a median
      particle size of about 0.3 microm was successfully developed. The particle size
      of the nanosuspension did not increase significantly during the lyophilization
      process and was stable for at least 39 days at room temperature after
      lyophilization. This approach of nanosizing a drug/carrageenan complex increased
      the aqueous solubility of the compound from less than 1 microg/mL to 39
      microg/mL. In addition to increasing aqueous solubility, a nanosized
      compound/carrageenan complex had a faster dissolution rate than the complex, the
      free compound, and the nanosuspension of the free compound.

PMID- 17560056
TI  - Influence of end groups on in vitro release and biological activity of lysozyme
      from a phase-sensitive smart polymer-based in situ gel forming controlled release
      drug delivery system.
AB  - Phase-sensitive in situ gel forming controlled release formulations of lysozyme
      were prepared using poly lactic acid (PLA) and/or poly glycolic acid (PGA) based
      polymers differing in end groups in addition to composition, and a solvent system
      consisting of various ratios of benzyl benzoate (BB) and benzyl alcohol (BA). The
      amount of lysozyme in the released samples was determined by measuring absorbance
      at 280 nm using suitable controls to nullify the effect of absorption of
      formulation degradation products. Biological activity of lysozyme was studied by
      an enzyme activity assay using Micrococcus lysodeikticus as substrate. Polymers
      bearing carboxylic acid end group were not soluble in 100% BB but polymers having
      ester end groups were soluble up to 27% (w/v) except polymer 4. A biphasic
      release profile consisting of slower first phase followed by faster second phase
      was observed. Formulations prepared from polymer with carboxylic acid groups
      showed significantly (p<0.05) lower burst release (4%) than those containing
      ester end groups (20-30%). However, formulations consisting of polymer with
      carboxylic acid end groups showed significantly (p<0.05) faster release rate of
      incorporated lysozyme, although the total amount released was less in comparison
      to the total amount released from formulations prepared using polymers containing
      ester end groups. The mean percentage specific enzyme activity (MPSEA) data were
      supported by the release profiles. In conclusion, polymer end groups may
      influence the release profiles of a protein from an in situ gel depot forming
      controlled release formulations.

PMID- 17560057
TI  - Effect of the unstirred water layer on permeability enhancement by hydrophilic
      cyclodextrins.
AB  - Saturated solutions of three test compounds, carbamazepine, griseofulvin and
      hydrocortisone, were prepared in aqueous buffer (pH 7.4) containing 0, 1, 5 and
      10% HPbetaCD. The permeability and flux of the drugs though a PAMPA membrane at
      different unstirred water layer (UWL) thicknesses was determined. In absence of
      HPbetaCD, permeability coefficients increased two- to three-fold with decreasing
      UWL thickness to a certain minimum values of about 40 microm. Addition of
      HPbetaCD to systems exhibiting larger UWL thicknesses significantly increased
      compound flux. The effect of HPbetaCD was linked to its association constant
      (K(1:1)) with the model drugs and decreased with decreasing UWL thickness to a
      certain minimum value. This suggests that hydrophilic cyclodextrins enhance flux
      when the UWL resistance significantly contributes to the overall barrier
      resistance.

PMID- 17560058
TI  - Poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles prepared by high pressure
      homogenization for paclitaxel chemotherapy.
AB  - High pressure homogenization was employed in the current work to prepare poly(D,L
      lactide-co-glycolide) (PLGA) nanoparticles (NPs) for controlled release of
      paclitaxel. The prepared drug-loaded PLGA NPs were found of spherical shape with
      a size of 200-300 nm. The drug encapsulation efficiency ranged from 34.8+/-1.6 to
      62.6+/-7.9% depending on the homogenization pressure and cycles. Paclitaxel was
      released from the nanoparticles in a biphasic profile with a fast release rate in
      the first 3 days followed by a slow first-order release. A higher or comparable
      cytotoxicity against glioma C6 cells was found for the drug formulated in the
      PLGA NPs in comparison with the free drug Taxol. Confocal laser scanning
      microscopy (CLSM) evidenced internalization of the fluorescent coumarin 6-loaded
      PLGA NPs by the C6 cells. The freeze-dried nanoparticles were found to possess
      excellent water redispersability. The high pressure homogenization could be
      applied for large industrial scale production of nanoparticles for drug delivery.

PMID- 17560059
TI  - An investigation into the presence of petrol on the clothing and shoes of members
      of the public.
AB  - First, the clothing and shoes from 29 participants who had recently filled their
      vehicles with petrol were analysed for any traces of petrol. No traces of petrol
      were found on any of these items. Secondly, the clothing and shoes from 17
      participants who had recently used a petrol-powered lawn mower were also analysed
      for petrol. Petrol was detected on two pairs of shoes from different
      participants. Components of petrol were detected on a set of clothing from a
      third participant, however, there were insufficient components present in this
      sample to confirm the presence of petrol. No traces of petrol were found on the
      items from the remaining 14 participants. Thirdly, the clothing from a forecourt
      attendant, a mechanic and a professional lawn mower were analysed at the end of a
      number of shifts. Petrol was detected on the upper and lower clothing from the
      forecourt attendant at the end of one shift. No petrol residues were found on the
      forecourt attendant after a second shift, or on the mechanic's clothing after two
      separate shifts or on the professional lawn mower's clothing after three separate
      shifts. These results can be used to assist the forensic analyst in assessing the
      chance of finding traces of petrol on clothing and shoes after the wearer has
      performed common activities that involve petrol.

PMID- 17560060
TI  - Dental age assessment using Demirjian's method on northern Turkish children.
AB  - Tooth formation is widely used to assess maturity and to predict age. Within
      clinical dentistry, such information aids in diagnosis and treatment planning.
      Numerous methods exist that allow either the prediction of age or an assessment
      of maturation. One widely used method was first described in 1973 by Demirjian et
      al., as based on a large number of French-Canadian children. The purpose of this
      study was to evaluate the applicability of Demirjian's method for dental age
      estimation and for description of mandibular permanent tooth formation in
      northern Turkish children, 4-12 years of age. Panoramic radiographs of 900
      healthy, northern Turkish children, 4-12 years of age were examined with
      Demirjian's method. Panoramic radiographs were scored by one examiner. Dental age
      was compared to chronological age by using a paired t-test. The median age for
      individual teeth for each stage was calculated. The northern Turkish children
      were generally advanced in dental maturity compared with the children in
      Demirjian's sample. The mean difference between dental and chronologic ages of
      boys and girls varied from 0.36 to 1.43 years and 0.50-1.44 years, respectively.
      The standards of dental age described by Demirjian et al. in 1973 and 1976 may
      not be suitable for northern Turkish children. Each population of children may
      need their own specific standard for an accurate estimation of chronological age.

PMID- 17560061
TI  - Forensic analysis of carbohydrate-deficient transferrin (CDT) by HPLC--statistics
      and extreme CDT values.
AB  - BACKGROUND: Carbohydrate-deficient transferrin (CDT) is the most specific serum
      marker of chronic alcohol abuse so far. There is little knowledge about extreme
      CDT values of >20% and the more >30% CDT. METHODS: Serum CDT/transferrin ratios
      from 19,236 serum samples sent to our laboratory for routine CDT analysis were
      determined by HPLC. About 75% of these serum samples were from traffic or
      employment medicine investigations. A CDT value frequency histogram was computed
      and extreme CDT values were clinically validated. RESULTS: Fourteen thousand four
      hundred and sixty-one CDT results were normal (< or =1.7%) and 4775 increased
      (1.8-36.9% CDT). Most frequent normal and increased results were 0.9% CDT
      (n=1964) and 1.8% CDT (n=356). CA. 70% of the pathological results were between
      1.8% and 5.0% CDT, ca. 88% between 1.8% and 10.0% CDT, and 98% between 1.8% and
      20.0%. CDT values >20.0% appeared in 79 cases and results >30.0% in two cases
      (33.8% and 36.9%). In each case of CDT values >20%, chronic alcohol abuse was the
      underlying cause as confirmed by anamnestic exploration. CONCLUSIONS:
      CDT/transferrin ratios are usually <20%. Higher values can appear in rare cases.
      CDT results >30% can be due to alcohol abuse but should be considered as
      remarkable single observations. Visualization of the transferrin isoform patterns
      by HPLC allows the detection of pathological transferrin isoform patterns and of
      genetic transferrin variants. This is essential for a reliable interpretation of
      (extreme) CDT values. CDT analysis by immunoassays without physico-chemical
      confirmatory analysis is no longer acceptable.

PMID- 17560062
TI  - Pharmacokinetics and bioavailability of gentiopicroside from decoctions of
      Gentianae and Longdan Xiegan Tang after oral administration in rats--comparison
      with gentiopicroside alone.
AB  - The pharmacokinetics and bioavailability of gentiopicroside (GPS), an active
      component of the Gentian plant species, from orally administered decoctions of
      Gentianae (DG), or in combination with other plants in the prescription of
      Longdan Xiegan Tang (LXT), was compared in rats with oral administration of GPS
      alone, using doses adjusted to deliver equivalent amounts of GPS (150 mg/kg).
      Changes in plasma levels of GPS following oral administration of GPS or DG could
      be fitted to a one compartment open model with elimination half times (T(1/2)Ke)
      of 3.35+/-0.76 h and 6.21+/-3.07 h, respectively. Kinetics of plasma GPS
      following oral administration of LXT could be fitted to a two compartments open
      model with an elimination half time (T((1/2)beta)) of 3.83+/-1.54 h. The
      bioavailability of GPS from DG was markedly better, and that from LXT markedly
      worse, compared with GPS alone, as judged by the area under concentration-time
      curve (AUC) values of 70.0+/-13.9 microgh/ml (DG), 32.7+/-12.9 microgh/ml (GPS)
      and 19.1+/-5.9 microgh/ml (LXT). The study demonstrates the marked variability in
      pharmacokinetics and bioavailability of an active component from different herbal
      preparations.

PMID- 17560063
TI  - Simultaneous determination of danshensu, ferulic acid, cryptotanshinone and
      tanshinone IIA in rabbit plasma by HPLC and their pharmacokinetic application in
      danxiongfang.
AB  - A selective and sensitive reversed-phase high performance liquid chromatography
      method was developed and validated for the simultaneous determination of
      danshensu, ferulic acid, cryptotanshinone, and tanshinone IIA in rabbit plasma
      using p-hydroxybenzoic acid as internal standard. Liquid-liquid extraction was
      used for sample preparation. Chromatographic separation was successfully achieved
      on an Agilent HC-C(18) column using a mobile phase composed of methanol-water
      (from 20:80 to 80:20, v/v) containing 0.5% (v/v) glacial acetic acid. The mobile
      phase was employing gradient elution at a flow rate of 1.0 ml/min. The method
      showed good linearity and no endogenous material interfered with the marked
      compounds and I.S. peaks. The limit of quantification of danshensu, ferulic acid,
      cryptotanshinone, and tanshinone IIA were 0.1, 0.03, 0.05, and 0.05 microg/ml,
      respectively. The average extract recoveries of the four compounds from rabbit
      plasma were all over 60%. The precisions determined from 5 days were all within
      10%. The established method has been successfully applied in the pharmacokinetic
      study and drug interaction of danshensu, ferulic acid, cryptotanshinone, and
      tanshinone IIA in rabbits after intravenous administration of danxiongfang, a
      useful compound preparation of traditional Chinese medicine.

PMID- 17560064
TI  - Simultaneous quantification of 14 ginsenosides in Panax ginseng C.A. Meyer
      (Korean red ginseng) by HPLC-ELSD and its application to quality control.
AB  - A new method of high-performance liquid chromatography coupled with evaporative
      light scattering detection (HPLC-ELSD) was developed for the simultaneous
      quantification of 14 major ginsenosides, which are the marker compounds of Panax
      ginseng C.A. Meyer (Korean red ginseng). Various types of ginseng samples were
      extracted, and the amounts of the 14 ginsenosides (Rg1, Re, Rf, Rh1, Rg2, Rb1,
      Rc, Rb2, Rb3, Rd, Rg3, Rk1, Rg5, and Rh2) were determined by reverse-phase HPLC
      ELSD using digoxin as an internal standard. The mobile phase consisted of a
      programmed gradient of aqueous acetonitrile. Calibration curves for each
      ginsenoside were determined for the quantification. The method was validated for
      linearity, precision, accuracy, limit of detection, and limit of quantification.
      This quantification method was applied to several finished ginseng products
      including white ginseng, red ginseng powder, and red ginseng concentrate. The
      amounts of the 14 ginsenosides in the various ginseng samples could be analyzed
      simultaneously. This validated HPLC method is expected to provide a new basis for
      the quality assessment of ginseng products.

PMID- 17560065
TI  - From primary care interventions to classical communication studies: papers from
      the EACH 2006 conference.

PMID- 17560066
TI  - The Oncosurge strategy for the management of colorectal liver metastases - an
      external validation study.
AB  - INTRODUCTION: Because most patients with colorectal liver metastases (CRLM)
      present to general surgeons and oncologists without a specialist interest in
      their management, a computer program (OncoSurge) has been created that identifies
      individual patient resectability and recommends optimal treatment strategies. The
      aim of this study was to validate the Oncosurge strategy by comparing its
      recommendations with the decisions made by a multidisciplinary (MDT) meeting, in
      a supra-regional hepatobiliary referral centre, using real cases with known
      outcomes. METHODS: We reviewed the records and imaging of 98 consecutive patients
      with CRLM, who had been referred for decision making to our MDT meeting between
      January 1, 2004 and December 31, 2004. All patient and tumour characteristics
      were entered onto the Oncosurge decision model, which was accessed at
      www.evidis.com/oncosurge/ RESULTS: There was concordance between Oncosurge and
      MDT decisions in 93/98 cases. The observed kappa (kappa) was 0.850 (95% CI: 0.728
      0.972). In descriptive terms, a kappa score greater than 0.8 equates to "almost
      perfect agreement". CONCLUSIONS: Our results demonstrate the validity of the
      Oncosurge system when compared to one year of decision making in an established
      hepatobiliary MDT meeting. This confirms the utility of the Oncosurge system for
      decision making, audit and educational purposes.

PMID- 17560067
TI  - Analysis of CCR5, CCR2, SDF1 and RANTES gene polymorphisms in subjects with HIV
      related PML and not determined leukoencephalopathy.
AB  - Progressive Multifocal Leukoencephalopathy (PML) is a fatal demyelinating disease
      of the central nervous system (CNS) caused by JC virus (JCV), a human
      polyomavirus that can lytically infect and destroy the oligodendrocites in
      immunosuppressed individuals. After the introduction of highly active
      antiretroviral therapy (HAART) for AIDS treatment, a PML-like
      leukoencephalopathy, known as non-determined leukoencephalopathy (NDLE), has also
      been observed. Since a number of host genetic factors have been identified as
      having an impact on susceptibility to HIV-1 infection and in the progression to
      AIDS and death, in this work we analysed the pattern of distribution of different
      chemokine and chemokine receptor polymorphisms that seem to be involved in HIV+
      neurological diseases. The CCR5, RANTES, CCR2 and SDF1 genes were molecularly
      analysed in 84 HIV+ HAART treated subjects: 55 without neurological disorders
      (HIV+), 12 HIV+ NDLE and 17 HIV+ PML patients. The RANTES -403 G/A polymorphism
      was significantly associated with NDLE. These data suggest that mutation of the
      RANTES allele can predispose to the induction of demyelination similarly to what
      has been observed in Multiple Sclerosis (MS) and may suggest a possible
      explanation for the development of leukoencephalopathy without detection of JCV.

PMID- 17560068
TI  - Decreased survival in pancreatic cancer patients with high concentrations of
      organochlorines in adipose tissue.
AB  - We analysed adipose tissue concentrations of persistent organic pollutants (POPs)
      in 21 cases with exocrine pancreatic cancer. The comparison group consisted of 59
      subjects. Significantly increased concentrations of polychlorinated biphenyls
      (PCBs), hexachlorobenzene (HCB), sum of chlordanes and polybrominated
      diphenylethers (PBDEs) were found in the cases. For 1,1,-dichloro-2,2-bis(p
      chlorophenyl)-ethylene (p,p'-DDE) no significant difference was seen. For PCBs no
      odds ratio (OR) could be calculated since all cases had concentration>median in
      controls used as a cut-off. HCB yielded OR=53.0, 95% confidence interval
      (CI)=4.64-605 and sum of chlordanes OR=18.4, 95% CI=2.71-124 whereas OR was not
      significantly increased for p,p'-DDE or PBDEs. Body mass index (BMI) at the time
      of tissue sampling was significantly lower for the cases. This might have
      influenced the results. Using BMI one year previously or decreasing the
      concentrations of POPs with the same percentage as weight loss among the cases
      did not change the results. Survival of the cases was shorter in the group with
      the concentration of POPs>median among cases, significantly so for the sum of
      PCBs (147 vs. 294 days), p,p'-DDE (134 vs. 302 days), and sum of chlordanes (142
      vs. 294 days) in the high and low group, respectively. The results were based on
      a low number of cases and should be interpreted with caution.

PMID- 17560069
TI  - [Atypical claudication and functional popliteal entrapment].
AB  - INTRODUCTION: Popliteal artery entrapment syndrome is infrequent. One form less
      well recognized has no anatomic abnormality. CASE REPORT: A 22-year old man, with
      a medical history of chronic compartment syndrome treated surgically by
      aponeurectomy, had developed intermittent claudication of both legs with plantar
      paresthesia. Active plantar flexion of the ankle reduced distal pulses and
      doppler ultrasound waveforms. Popliteal artery entrapment syndrome was suspected
      and was confirmed by dynamic angiography. Because no arterial ou muscular
      abnormalities were found, we diagnosed a functional popliteal entrapment
      syndrome. Surgical treatment permitted rapid functional improvement. DISCUSSION:
      Positional occlusion of the popliteal artery is a normal physiologic variant that
      may become pathologic with muscle overuse or traumatic injury. It causes
      neuromuscular claudication by compressing the neurovascular bundle at the level
      of the soleal sling. Diagnosis is based on dynamic color-flow duplex imaging and
      magnetic resonance angiography. Surgical treatment is indicated only for
      symptomatic patients and consists of fasciotomy, resecting the compressing
      structures with a posterior or medial approach.

PMID- 17560070
TI  - [Elastofibroma dorsi: a differential diagnosis in subscapular soft tissue
      tumors].

PMID- 17560071
TI  - [Acute Datura stramonium poisoning in an emergency department].
AB  - BACKGROUND: The toxic effects of Datura stramonium most often include visual and
      auditory hallucinations, confusion and agitation. Severe and even fatal
      complications (coma, respiratory distress or death in more than 5% of cases) are
      not rare since the lethal concentration of the drug's toxic substances (i.e.,
      atropine and scopolamine) is close to the level at which delirium occurs. CASES:
      A 17-year-old man was admitted to our emergency department with agitation,
      delirium with persecutory ideation and frightening hallucinations of being
      assaulted by animals. Blood samples taken 12 hours after Datura stramonium
      ingestion and analyzed with liquid chromatography and mass spectrometry (LC
      MS/MS) found 1.7 ng/mL of atropine, close to the lethal level. After restraint
      and treatment with the antipsychotic drug cyamemazine, the young man returned to
      normal 36 hours after drug ingestion. A 17-year-old woman was admitted to our
      emergency department after losing consciousness on a public thoroughfare. At the
      emergency department, 2 hours after she had ingested Datura stramonium, she was
      agitated, with delirium, anxiety, and frightening visual and tactile
      hallucination of green turtles walking on her as well as auditory hallucinations.
      Blood samples at D0, D1 and D2 after Datura stramonium ingestion, analyzed with
      LC-MS/MS, found: 1.4, 1.0, and 0.2 ng/mL of scopolamine, respectively. Atropine
      was massively eliminated in urine on D1 (114 ng/mL). After restraint and
      cyamemazine treatment, the young woman returned to normal 40 hours after she had
      first ingested this hallucinogen. DISCUSSION: These cases of intoxication with
      Datura stramonium are, to our knowledge, the first clinical reports correlated
      with toxicologic analysis by the reference method (LC-MS/MS) in an emergency
      setting. Since neither the drug-users nor those accompanying them usually
      volunteer information about drug use, it is important to consider this specific
      risk in cases of agitation and confusion in adolescents or young adults.

PMID- 17560072
TI  - Developing a high-throughput system for the screening of cytochrome P450 1A1-
      inhibitory polyphenols.
AB  - Polycyclic aromatic hydrocarbons (PAH) are established procarcinogens that can be
      found in our environment. The carcinogenicity of these compounds is initiated by
      their metabolic intermediates, and the extent of biotransformation determines the
      amount of reactive intermediates generated. CYP1A1 is a major enzyme that
      metabolizes PAH into carcinogenic moieties. Since previous studies have shown
      that increased CYP1A1 activity is associated with a higher cancer risk.
      Identifying CYP1A1-inhibitory compounds in diet or natural products are of
      genuine interest for chemoprevention studies. In this project, a stable cell line
      expressing human CYP1A1 was established for the screening of potential
      chemopreventive agents. Because of a lacking cellular transport mechanism in
      assays performed on recombinant protein, an 'in-cell' assay system might be a
      better estimate at the tissue level. Theaflavins were strong inhibitors of
      ethoxyresorufin-O-deethylase (EROD) activity when assayed on recombinant human
      CYP1A1 protein. However, this inhibition was not observed in the CYP1A1
      expressing cells. The 'in-cell' IC50 values determined for compounds such as
      genistein, quercetin, chalcone, etc. were comparable to the values determined in
      recombinant protein. This 'in-cell' assay has the additional advantages of short
      sample processing time, and the tedious procedures of protein expression and
      purification can be waived.

PMID- 17560073
TI  - TCMS inhibits ATP synthesis in mitochondria: a systematic analysis of the
      inhibitory mechanism.
AB  - The interactions of the antifouling compound TCMS (2,3,5,6-tetrachloro-4
      methylsulphonyl pyridine) with rat liver mitochondria have been investigated. The
      results indicate that the compound inhibits ATP synthesis. Further investigations
      regarding the ATP synthesis mechanism suggest that TCMS inhibits succinic
      dehydrogenase of the mitochondrial respiratory chain. As the respiratory chain is
      similar in all living organisms, it can be concluded that the toxic effect of
      TCMS most likely depend on the different bioavailability of the compound and on
      the different importance of mitochondria in the ATP production in the animal
      species.

PMID- 17560074
TI  - The development and evaluation of a single step multiplex PCR method for
      simultaneous detection of Brugia malayi and Wuchereria bancrofti.
AB  - A single step novel multiplex polymerase chain reaction (PCR) has been developed
      for simultaneous detection of human filarial parasites, Brugia malayi and
      Wuchereria bancrofti, from blood samples and mosquitoes. The primers used were
      novel and have been tested with the parasite DNA amplifying 188bp (BM) and 129bp
      (WB) DNA fragments, specific to B. malayi and W. bancrofti, respectively, in a
      single reaction. The specificity of the PCR product was confirmed by DNA
      sequencing and slot blot hybridization assay. The test was found highly sensitive
      for both B. malayi and W. bancrofti by detecting the parasitaemia up to the level
      of one microfilaria per reaction. The assay was further evaluated on 98 blood
      samples and 144 mosquito samples collected from filarial endemic areas. The PCR
      was found to be more efficient in comparison to microscopy by detecting 8% and 5%
      more filarial parasites in field-collected blood and mosquito samples,
      respectively. This novel PCR that offers scope for simultaneous detection of both
      the parasites may be used as a diagnostic tool for the detection of filariasis in
      population and can be adopted for rapid surveillance and monitoring of mosquitoes
      for use in the effective control of filariasis.

PMID- 17560075
TI  - Distribution and morphology of cholinergic, catecholaminergic and serotonergic
      neurons in the brain of Schreiber's long-fingered bat, Miniopterus schreibersii.
AB  - The current study describes the nuclear parcellation and neuronal morphology of
      the cholinergic, catecholaminergic and serotonergic systems within the brain of a
      representative species of microbat. While these systems have been investigated in
      detail in the laboratory rat, and examined in several other mammalian species, no
      chiropterans, to the author's knowledge, have been examined. Using
      immunohistochemical stains for choline-acetyltransferase, tyrosine hydroxylase
      and serotonin, we were able to observe and document these systems in relation to
      the cytoarchitecture. The majority of cholinergic nuclei typically found in
      mammals were evident in the microbat, however we could not find evidence for
      choline-acetyltransferase immunopositive neurons in the Edinger-Westphal nucleus,
      parabigeminal nucleus, and the medullary tegmental field, as seen in several
      other mammalian species. A typically mammalian appearance of the
      catecholaminergic nuclei was observed, however, the anterior hypothalamic groups
      (A15 dorsal and ventral), the dorsal and dorsal caudal subdivisions of the
      ventral tegmental area (A10d and A10dc), and the ventral (pars reticulata)
      substantia nigra (A9v) were not present. The serotonergic nuclei were similar to
      that reported in all eutherian mammalian species studied to date. The overall
      complement of nuclei of these systems in the microbat, while different to the
      species examined in other orders of mammals, resembles most closely the
      complement seen in earlier studies of insectivore species, and is clearly
      distinguished from that seen in rodents, carnivores and primates. This data is
      discussed in terms of the phylogenetic relationships of the chiropterans.

PMID- 17560076
TI  - Continuous transesophageal monitoring for thrombolytic therapy of an acute
      prosthetic mitral valve thrombosis.

PMID- 17560077
TI  - Islet autoantibody development during follow-up of high-risk children from the
      general Norwegian population from three months of age: design and early results
      from the MIDIA study.
AB  - We describe the design of the MIDIA study and present serial islet autoantibody
      data from 3 months of age in the 526 first enrolled children from the general
      population carrying the type 1 diabetes high-risk HLA-DRB1*0401-DQA1*03
      DQB1*0302/DRB1*0301-DQA1*05-DQB1*02 genotype. Blood samples were obtained from
      children at ages 3, 6, 9 and 12 months and annually thereafter to a median age of
      12 months. Autoantibodies to insulin, glutamic acid decarboxylase and insulinoma
      associated antigen-2 were measured with radiobinding assays. About 25,000 general
      population newborns were genotyped, and among 526 children with the high-risk HLA
      genotype, 2104 samples were assayed. Fourteen children were positive in at least
      two consecutive samples, including 12 who were positive for > or =2
      autoantibodies at least once, of which five developed type 1 diabetes at median
      age 15.3 months. Seven of 14 persistently positive children seroconverted before
      9 months, including two before 6 months of age. The estimated cumulative
      probability of multiple autoantibody positivity at 5 years was 7.3% (95%
      confidence interval: 3.5-12.4%). Thus, persistent islet autoimmunity is not
      uncommon in the first year of life in children from the general population
      carrying the high-risk HLA genotype, and may develop as early as at 6 months of
      age.

PMID- 17560078
TI  - Receptor-coupling properties of the invertebrate visual guanine nucleotide
      binding protein iGqalpha.
AB  - Invertebrate visual iG(q)alpha is homologous to mammalian mG(q)alpha in two of
      the three domains important for G protein interaction with receptors; the C
      terminus and the linker regions that connect the helical and ras-like domains of
      the alpha subunit. The third receptor-interacting domain, the N-terminus,
      contains a six amino acid extension MTLESI in mG(q)alpha that is not present in
      iG(q)alpha. In co-expression studies we assessed the promiscuity and efficacy of
      receptor coupling to phospholipase C (PLC) by iG(q)alpha, a non-palmitoylated
      mutant iG(q)alpha(C3,4A), mG(q)alpha and G(15)alpha. The invertebrate G proteins
      and mG(q)alpha only coupled to G(q)-coupled receptors (m1 muscarinic
      acetylcholine receptor (mChR1), alpha(1A)-adrenergic receptor (alpha1-AR)) and
      not to the G(i/s)-coupled receptors (CCR1 receptor, beta2-adrenergic receptor or
      dopamine D1 receptor) while G(15)alpha coupled to all receptors. iG(q)alpha and
      iG(q)alpha(C3,4A) both had double the efficacy for PLC activation compared to the
      mammalian G proteins when co-expressed with mChR1 and alpha1-AR. The increased
      efficacy of iG(q)alpha compared to mG(q)alpha was also seen downstream of PLC
      with carbachol stimulation of the mitogen-activated protein kinase, ERK1/2.
      Addition of the MTLESI extension onto the N-terminus of iG(q)alpha decreased its
      efficacy by 35% whereas deletion of this sequence from mG(q)alpha increased its
      efficacy by 60% in the PLC and ERK1/2 assays. iG(q)alpha, iG(q)alpha(C3,4A) and
      mG(q)alpha all displayed similar receptor-independent AlF(4)(-)activation of PLC
      and guanosine triphosphate hydrolysis (GTPase) activity. iG(q)alpha, and
      iG(q)alpha(C3,4A) both had increased receptor-activated guanosine 5'-[gamma
      [(35)S]thio]triphosphate ([(35)S]GTPgammaS) binding when compared to mG(q)alpha
      when co-expressed with the mChR1. These results demonstrate that G(q) protein
      efficacy is at least partially determined by the presence of the amino-terminal
      MTLESI extension. Comparison of [(35)S]GTPgammaS binding rates helps explain the
      increased efficacy of the invertebrate G proteins.

PMID- 17560079
TI  - Influence of G308A polymorphism of tumor necrosis factor-alpha gene on
      inflammatory markers in postsurgical head and neck cancer patients with early
      enteral nutrition.
AB  - OBJECTIVE: Although immune dysfunction in patients with cancer could be
      multifactorial, the immune system may be modulated by nutritional substrates and
      genetic background. Our study evaluated the effect of G308A polymorphism of the
      tumor necrosis factor-alpha (TNF-alpha) gene on inflammatory markers in patients
      after surgery for head and neck cancer who received early enteral nutrition.
      METHODS: A population of 60 patients with oral and laryngeal cancer was enrolled.
      At surgery patients were treated with a hyperproteic enteral diet.
      Perioperatively and on postoperative day 6 the following parameters were
      evaluated: serum values of prealbumin, transferrin, total number of lymphocytes,
      interleukin-6, TNF-alpha, and C-reactive protein. In addition, genotyping of
      G308A gene polymorphism was assessed. RESULTS: Patients' mean age was 61.1 +/-
      14.6 y (four women, 56 men) with a body mass index of 25.4 +/- 5.2 kg/m(2) and a
      previous weight loss of 0.35 +/- 0.2 kg. Forty patients (37 men, 3 women; 66.6%)
      had the genotype G308/G308 (wild group) and 20 patients (19 men, 1 woman; 23.4%)
      had the genotype G308/A308 (mutant group). A significant increase in prealbumin
      and transferrin levels was detected in both groups. C-reactive protein decreased
      in both groups (wild group: 105.1 +/- 60 versus 53.8 +/- 62.3 mg/dL, P < 0.05;
      mutant group: 99.5 +/- 46 versus 43.9 +/- 51.9 mg/dL, P < 0.05). Interleukin-6
      decreased in both groups (wild group: 20.1 +/- 22 versus 6.2 +/- 4.1 pg/mL, P <
      0.05; mutant group: 22.3 +/- 38 versus 9.2 +/- 7.4 pg/mL, P = NS). Lymphocytes
      increased in both groups (wild group: 1102 +/- 468 versus 1600 +/- 537 10(3)/mL,
      P = NS; mutant group: 1441 +/- 739 10(3)/mL versus 1669 +/- 614 10(6)/mL, P =
      NS). TNF-alpha showed no changes. CONCLUSION: The G308A polymorphism of the TNF
      alpha gene did not affect levels of inflammatory markers in patients after
      surgery for head and neck cancer who were treated with early enteral nutrition.

PMID- 17560080
TI  - Effect of a weight-loss program on mental stress-induced cardiovascular responses
      and recovery.
AB  - OBJECTIVE: We assessed the effect of weight loss on blood pressure (BP) and pulse
      rate during rest, psychological stress, and recovery after stress. METHODS: Two
      groups of men completed two mental stress tests 12 wk apart. The control group
      continued their usual diet, whereas the weight-loss group underwent a dietary
      weight-loss program in which they were randomized to a high-fruit/vegetable and
      low-fat dairy diet or a low-fat diet. RESULTS: Fifty-five men with a baseline BP
      of 125.9 +/- 6.9/83.6 +/- 7.1 mmHg (mean +/- SD) completed the study (weight-loss
      group, n = 28; control group, n = 27). The weight-loss group lost weight (mean +/
      SEM, -4.3 +/- 0.3 versus +0.4 +/- 0.4 kg, P = 0.001) compared with controls and
      had a significant decrease in resting systolic BP (SBP; -2.0 +/- 1.1% versus +2.0
      +/- 1.1%, P < 0.05). There was a greater decrease in SBP (P < 0.05) and pulse
      rate (P < 0.05) at all time points during the stress test in the weight loss
      compared with the control group. At week 12, SBP in 23 (82%) subjects in the
      weight-loss group and 24 (89%) in the control group returned to resting levels,
      with recovering levels in the weight-loss group returning to resting levels 6.1
      +/- 2.6 min earlier than in the control group (P < 0.05). There was an overall
      greater decrease in diastolic BP (DBP; P < 0.05) and DBP during recovery up to 27
      min after stress (P < 0.05) in the high-fruit/vegetable and low-fat dairy diet
      group (n = 14) compared with the low-fat diet group (n = 14). CONCLUSION: A 5%
      loss of weight decreased BP during rest and returned SBP to resting levels
      faster, thus decreasing the period of increased BP as a result of mental stress,
      which is likely to lower the risk of cardiovascular disease in the long term.

PMID- 17560081
TI  - Enteral nutrition affects nitric oxide production in peripheral blood and liver
      after a postoperative lipopolysaccharide-induced endotoxemia in rats.
AB  - OBJECTIVES: Sepsis is a common complication in the early postoperative period,
      leading to the augmentation of oxidative and nitrosative stresses. The present
      study investigated the role of enteral nutrition on nitric oxide (NO) production
      after a lipopolysaccharide (LPS)-induced endotoxemia as an index of nitrosative
      stress. METHODS: Fifty rats were subjected to midline laparotomy and feeding
      gastrostomy. Ten rats served as controls after recovering from operative stress.
      The remaining rats received, through gastrostomy, enteral nutrition or placebo
      feeding for 24 h, after which they were injected intraperitoneally with LPS or
      equal volume of saline. Two hours later blood and liver tissue were collected. NO
      production was quantified in serum samples and homogenates of liver tissue by a
      modification of Griess's reaction. NO synthase (NOS) mRNA expression was examined
      in homogenate of liver tissue by reverse transcription-polymerase chain reaction.
      RESULTS: The operation significantly increased basal NO production in rat serum.
      LPS induced a further significant increase of NO levels. Enteral feeding of rats
      significantly decreased NO levels in both groups. In contrast, enteral nutrition
      was found to increase significantly NO levels in liver homogenates from rats
      treated with LPS. A constitutive endothelial NOS mRNA expression was found in
      liver tissue, whereas LPS administration induced inducible NOS mRNA expression in
      liver tissue regardless of enteral feeding. CONCLUSION: These findings indicate
      that early enteral feeding leads to a reduction in circulating NO levels induced
      by operation and endotoxemia, but increases hepatic NO levels in endotoxemia
      probably by the effect of LPS-induced inducible NOS on the increased L-arginine
      uptake.

PMID- 17560082
TI  - Intraoperative navigation in the maxillofacial area based on 3D imaging obtained
      by a cone-beam device.
AB  - The aim of this study was to evaluate intraoperative navigation in the
      maxillofacial area based on three-dimensional imaging obtained by a cone-beam
      device. Digital volume tomograms (DVT) were obtained by the prototype of GALILEOS
      (Sirona Dental Systems Inc., Bensheim, Germany), a newly developed, compact size,
      cone-beam machine with a scan volume of 15 cm x 15 cm x 15 cm. Intraoperative
      navigation was performed in 12 patients in three selected indications. Target
      detection error expressing the accuracy of DVT navigation and registration
      performance of specially developed methods for image-to-patient registration was
      estimated. Target detection error was maximally 2 mm and depended on the
      registration method chosen. The automatic detection rate of the fiducial markers
      ranged between 0.64 and 0.32. The preoperatively defined treatment plan was fully
      accomplished in 11 out of 12 cases. A favourable surgical outcome was achievable
      in all cases. Intraoperative complications were not observed. Intraoperative
      navigation based on DVT imaging can be considered as a valuable alternative to CT
      based procedures. Special characteristics of the cone-beam technique, in terms of
      contrast resolution and the limited field-of-view size of the devices, restrict
      the indication spectrum and create a demand for modifications of the usual
      registration methods.

PMID- 17560083
TI  - Cognition and functional outcome among deaf and hearing people with
      schizophrenia.
AB  - Recent research has highlighted the relationships between impairments in
      cognitive functioning and poorer functional outcomes among people with
      schizophrenia (PWS). The purpose of this study was to replicate and extend this
      work by testing the relationships between cognition and functional outcome among
      deaf adults with schizophrenia. Empirical findings from deafness-oriented
      research reveals enhanced abilities in certain aspects of visual-spatial
      processing compared to hearing people. Sixty-five PWS (34 deaf, 31 hearing) were
      assessed using measures of verbal and visual memory, attention, and visual
      processing. The first hypothesis tested whether cognition predicted functional
      outcome in a similar fashion for both deaf and hearing subjects (n=63). For all
      subjects, higher levels of cognitive ability were associated with higher levels
      of functional outcome, and the strongest predictors of outcome were verbal memory
      and visual-spatial memory (recall condition) (VSM recall). However, the deaf and
      hearing groups did show different patterns of relationships between cognition and
      functioning when all cognitive variables were examined. The second hypothesis was
      that deaf subjects would display superior performance in early visual processing,
      visual-spatial memory (copy condition) (VSM copy), and VSM recall. Deaf subjects
      displayed superior performance on each task; however, no significant differences
      emerged. Deaf subjects outperformed hearing subjects in an unexpected domain
      (word memory/recognition). This study extends prior work in the area of cognition
      and schizophrenia and indicates that deaf and hearing subjects may benefit from
      interventions that address different domains of cognition.

PMID- 17560084
TI  - Establishment of SV40T-transformed human dermal papilla cells and identification
      of dihydrotestosterone-regulated genes by cDNA microarray.
AB  - BACKGROUND: Recent studies suggest that androgens are the main regulator of
      changes in human hair growth, and dermal papilla (DP) is known to secret factors
      which regulate the growth and activity of the cells in the follicle in response
      to androgens. However, published data of androgen-regulated genes in human dermal
      papilla cells is limited and genome-wide large scale screening has not been
      reported. OBJECTIVE: To identify the dihydrotestosterone (DHT)-regulated genes in
      human dermal papilla cells. METHODS: SV40T-transformed human dermal papilla cell
      line (SV40T-DPC) was established and DHT-regulated genes were screened by cDNA
      microarray analysis. RESULTS: SV40T-DPC maintained early passage morphology and
      expressed functional androgen receptors. cDNA microarray followed by RT-PCR
      analysis showed that a number of genes are regulated by DHT in SV40T-DPC.
      CONCLUSION: The DHT-regulated genes reported in this study may be involved in
      androgen-mediated regulation of hair growth.

PMID- 17560085
TI  - Impact of infection control interventions and antibiotic use on hospital MRSA: a
      multivariate interrupted time-series analysis.
AB  - Hospitals in the northeast of Scotland have experienced methicillin-resistant
      Staphylococcus aureus (MRSA) outbreaks since 1997. Several infection control
      measures were introduced sequentially to control MRSA, and antibiotic use has
      been monitored. From January 1997 to December 2004, data on the monthly
      percentage of non-duplicate MRSA infections (%MRSA) were collated from an
      intervention hospital (IH) and a control hospital (CH). Both hospitals introduced
      the use of alcohol hand gel in November 2002. Furthermore, the IH introduced an
      environmental MRSA swabbing programme in March 2001, chlorine disinfection of the
      environment in September 2001, discharge screening in December 2001, admission
      screening in November 2003 and environmental audits in March 2004. Multivariate
      dynamic regression analysis was used to evaluate the longitudinal effects of
      these interventions as measured by new clinical cases of MRSA. At the IH, the
      %MRSA increased between January 1998 and January 2001 and then decreased. At the
      CH, the %MRSA increased from January 1997 to December 2004. Introduction of
      alcohol hand gel was associated with an absolute decrease in %MRSA of 21% and
      30%, respectively, for the IH and CH. At the IH, introduction of chlorine
      disinfection and environmental swabbing were, respectively, associated with a
      decrease in %MRSA of 27% immediately and 32% 3 months later. Discharge screening
      and environmental audit did not significantly affect %MRSA, whereas admission
      screening was associated with a 22% decrease in %MRSA 4 months later. Increasing
      macrolide use was associated with increasing %MRSA in both hospitals, and
      increasing quinolone use was associated with increasing %MRSA in the CH.
      Implementation of stepwise infection control measures was associated with a
      decrease in %MRSA in the IH. Introduction of an alcohol gel for hand hygiene was
      associated with a decrease in %MRSA in both hospitals. Antibiotic use also
      affects %MRSA, in particular that of macrolides and quinolones.

PMID- 17560086
TI  - Effect of aminoglycoside dosing on magnesium levels in hospitalised patients.

PMID- 17560088
TI  - Apolipoprotein e deficiency leads to altered brain uptake of alpha tocopherol
      injected into lateral cerebral ventricles.
AB  - The incorporation of radioactive alpha tocopherol by various brain regions of
      wild type and apolipoprotein E (apoE)-deficient mice was investigated. Labeled
      tocopherol was injected into the lateral cerebral ventricles of 11 weeks old,
      male mice. Radioactive cholesterol injected simultaneously was used as an
      internal standard to account for experimental variability. Most areas of the
      brain of apoE-deficient mice took up less of alpha tocopherol per mg of protein
      than wild type animals. However, specific activity of alpha tocopherol was higher
      in cerebellum, pons, hypothalamus, midbrain and cerebral cortex in apoE-deficient
      brains than the wild type. This could be due to (a) the lower levels of alpha
      tocopherol in apoE-deficient brain and (b) reductions in the clearance and
      transport of tocopherol (possibly mediated by apoE). Tocopherol uptake by
      hippocampus was unusual since it was lower in apoE deficiency whether the data
      were expressed as specific activity or per mg of protein. Nearly all of the
      injected alpha tocopherol remained unchanged in the brains of both apoE-deficient
      and wild type animals suggesting low turnover. Overall, the current data
      reinforce the hypothesis that apoE is a key protein involved with the transport
      and/or retention of alpha tocopherol in brain.

PMID- 17560087
TI  - TRPs in bladder diseases.
AB  - This review attempts to provide an overview of the current knowledge of TRP
      proteins and their possible role in bladder function and disease. At present,
      there are 28 transient receptor potential (TRP) channels (subdivided into 7
      categories or families) which are involved in a number of functions [G.A. Hicks,
      TRP channels as therapeutic targets: hot property, or time to cool down?
      Neurogastroenterology and Motility 18, (2006) 590-594., J.D. Levine, N.
      Alessandri-Haber, TRP channels: targets for the relief of pain, Biochimica et
      Biophysica Acta 1772, (2007) 989-1003.]. Of those belonging to the group 1
      subfamily, a number of TRPV, TRPM and TRPA proteins associated with
      osmoregulation, thermal, chemical and mechanical signaling mechanisms have been
      shown to be expressed within the lower urinary tract. Though the biological role
      of many of these channels in urinary bladder function still remains elusive,
      TRPV1 is by far the best characterized and is thought to be involved in a number
      of bladder disorders [A. Szallasi, P.M. Blumberg, Vanilloid (Capsaicin) Receptors
      and Mechanisms, Pharmacological Reviews 51, (1999) 150-221., I. Nagy, P. Santha,
      G. Jansco, L. Urban, The role of the vanilloid (capsaicin) receptor (TRPV1) in
      physiology and pathology, European Journal of Pharmacology 500, (2004) 351-369.].

PMID- 17560089
TI  - Scrapie: uncertainties, biology and molecular approaches.
AB  - The study of the biology of scrapie in sheep is irretrievably associated with the
      genetics of the PrP gene in sheep. Control of susceptibility and resistance is so
      closely linked to certain alleles of the sheep PrP gene that no review on scrapie
      can avoid PrP genetics. Before the importance of PrP protein was discovered and
      before the influence of the gene itself on disease incidence was understood, it
      was clear there were some sheep which were more susceptible to natural scrapie
      than others and that this feature was heritable. These early observations have
      led to the development and use of PrP genotyping in sheep in what is probably the
      biggest genetic selection process ever attempted. The accompanying increase in
      surveillance has also discovered a novel type of scrapie, the subject of much
      speculation about its origin.

PMID- 17560090
TI  - A (27)Al MAS NMR study of a sol-gel produced alumina: Identification of the NMR
      parameters of the theta-Al(2)O(3) transition alumina phase.
AB  - (27)Al MAS NMR has been used to study a sol-gel prepared alumina annealed at
      various temperatures. Two-field simulation of the sample heated to 1200 degrees C
      confirmed the presence of corundum, as suggested by XRD, and also the presence of
      nanocrystalline theta-Al(2)O(3). (27)Al MAS NMR chemical shifts, quadrupolar
      coupling constants and asymmetry parameters are reported for the tetrahedral and
      octahedral aluminium sites within theta-Al(2)O(3).

PMID- 17560091
TI  - Simultaneous effects of relaxation and polarization transfer in LaF3-type
      crystals as sources of dynamic information.
AB  - Fluorine nuclear magnetic resonance (NMR) spin-lattice relaxation dispersion has
      been measured for pure LaF(3) and La(1-x)Sr(x)F(3-x) for admixture concentrations
      x ranging from 0.01% up to 16%. The relaxation dispersion experiments have been
      carried out in a wide frequency range (20 kHz-40 MHz) at temperatures between 300
      and 1400 K. The data have been analyzed using the recently published [J. Magn.
      Res. 179 (2006) 250] relaxation model for multispin systems of mutually
      interacting quadrupolar and dipolar nuclei. Rate constants of the fluorine ionic
      jumps within and among distinct fluorine sublattices have been extracted.
      Characteristic effects of the polarization transfer between fluorine and
      lanthanum spins have been observed and attributed to slow dynamics within one of
      the fluorine sublattices.

PMID- 17560092
TI  - Changes of antioxidative enzymes and cell membrane osmosis in tomato colonized by
      arbuscular Mycorrhizae under NaCl stress.
AB  - Salinity toxicity is a worldwide agricultural and eco-environmental problem. Many
      literatures show that arbuscular mycorrhizal fungi (AMF) can enhance salt
      tolerance of many plants and some physiological changes occurred in AM symbiosis
      under salt stress. However, the role of ROS-scavenging enzymes in AM tomato is
      still unknown in continuous salt stress. This study investigated the effect of
      Glomus mosseae on tomato growth, cell membrane osmosis and examined the
      antioxidants (superoxide-dismutase, SOD; catalase, CAT; ascorbate peroxidase,
      APX; peroxidase, POD) responses in roots of mycorrhizal tomato and control under
      different NaCl stress for 40 days in potted culture. NaCl solution (0, 0.5 and
      1%) was added to organic soil in the irrigation water after 45 days inoculated by
      AMF (Glomus mosseae). (1) AMF inoculation improved tomato growth under salt or
      saltless condition and reduced cell membrane osmosis, MDA (malonaldehyde) content
      in salinity. So the salt tolerance of tomato was enhanced by AMF; (2) SOD, APX
      and POD activity in roots of AM symbiosis were significantly higher than
      corresponding non-AM plants in salinity or saltless condition. However, CAT
      activity was transiently induced by AMF and then suppressed to a level similar
      with non-AM seedlings; (3) higher salinity (1% level) and long stress time
      suppressed the effect of AMF on SOD, APX, POD and CAT activity; (4) this research
      suggested that the enhanced salt tolerance in AM symbiosis was mainly related
      with the elevated SOD, POD and APX activity by AMF which degraded more reactive
      oxygen species and so alleviated the cell membrane damages under salt stress.
      Whereas, the elevated SOD, POD and APX activity due to AMF depended on salinity
      environment.

PMID- 17560093
TI  - Miscibility and interaction between 1-alkanol and short-chain phosphocholine in
      the adsorbed film and micelles.
AB  - The miscibility and interaction of 1-hexanol (C6OH) and 1-heptanol (C7OH) with
      1,2-dihexanoyl-sn-glycero-3-phosphocholine (DHPC) in the adsorbed films and
      micelles were investigated by measuring the surface tension of aqueous C6OH-DHPC
      and aqueous C7OH-DHPC solutions. The surface density, the mean molecular area,
      the composition of the adsorbed film, and the excess Gibbs energy of adsorption
      g(H,E), were estimated. Further, the critical micelle concentration of the
      mixtures was determined from the surface tension versus molality curves; the
      micellar composition was calculated. The miscibility of the 1-alkanols and DHPC
      molecules in the adsorbed film and micelles was examined using the phase diagram
      of adsorption (PDA) and that of micellization (PDM). The PDA and the composition
      dependence of g(H,E) indicated the non-ideal mixing of the 1-alkanols and DHPC
      molecules due to the attractive interaction between the molecules in the adsorbed
      film, while the PDM indicated that the 1-alkanol molecules were not incorporated
      in the micelles within DHPC rich region. The dependence of the mean molecular
      area of the mixtures on the surface composition suggested that the packing
      property of the adsorbed film depends on the chain length of 1-alkanol: C6OH
      expands the DHPC adsorbed film more than C7OH.

PMID- 17560094
TI  - Alterations in osmoregulation, antioxidant enzymes and indole alkaloid levels in
      Catharanthus roseus exposed to water deficit.
AB  - Catharanthus roseus (L.) G. Don plants were grown in different water regimes in
      order to study the drought induced osmotic stress and proline (PRO) metabolism,
      antioxidative enzyme activities and indole alkaloid accumulation. The plants
      under pot culture were subjected to 10, 15 and 20 days interval drought (DID)
      stress from 30 days after sowing (DAS) and regular irrigation was kept as
      control. The plants were uprooted on 41DAS (10DID), 46DAS (15DID) and 51DAS
      (20DID). The drought stressed plants showed increased aminoacid (AA), glycine
      betaine (GB) and PRO contents and decreased proline oxidase (PROX) and increased
      gamma-glutamyl kinase (gamma-GK) activities when compared to control. The
      antioxidative enzymes like peroxidase (POX) and polyphenol oxidase (PPO)
      increased to a significant level in drought stressed plants when compared to
      control. The drought stressed C. roseus plants showed an increase in total indole
      alkaloid content in shoots and roots when compared to well-watered control
      plants. Our results suggest that the cultivation of medicinal plants like C.
      roseus in water deficit areas would increase its PRO metabolism, osmoregulation,
      defense system and the level of active principles.

PMID- 17560095
TI  - Nanoparticles of hydrophobically modified dextrans as potential drug carrier
      systems.
AB  - Nanoparticles combining a hydrophobically modified dextran core and a
      polysaccharide surface coverage were elaborated. Their suitability for
      applications like drug delivery was evaluated. The selected polysaccharide,
      dextran, was chemically modified by the covalent attachment of hydrocarbon groups
      (aliphatic or aromatic) via the formation of ether links. According to the extent
      of modification, either water-soluble or water-insoluble dextran derivatives were
      obtained. The latter exhibited solubility in organic solvents like
      tetrahydrofuran or dichloromethane saturated with water. Water-soluble dextran
      derivatives were used as polymeric surfactants for the control of nanoparticles
      surface characteristics. Nanoparticles were prepared either by o/w emulsion or
      solvent-diffusion methods. The size and surface properties of dextran
      nanoparticles were correlated to processing conditions. The stability of
      colloidal suspensions was examined as a function of ionic strength and related to
      the particle surface characteristics. The redispersability of freeze-dried
      suspensions without the addition of cryoprotectant was demonstrated. Finally, the
      degradability of modified dextrans was compared to that of starting dextran,
      after enzymatic hydrolysis in the presence of dextranase.

PMID- 17560096
TI  - Different impacts of intestinal lymphatic transport on the oral bioavailability
      of structurally similar synthetic lipophilic cannabinoids: dexanabinol and PRS
      211,220.
AB  - The aim of this article was to investigate the role of intestinal lymphatic
      transport in the oral bioavailability of two structurally similar synthetic
      lipophilic cannabinoids: dexanabinol and PRS-211,220. For this purpose, the long
      chain triglyceride (LCT) solubility and affinity to chylomicrons ex vivo of both
      cannabinoids were evaluated. Their oral bioavailability was assessed in rats
      following administration in a lipid-free and a LCT-based formulation. The
      intestinal lymphatic transport of these two molecules was also directly measured
      in a freely moving rat model. LCT solubility of dexanabinol and PRS-211,220 was
      7.9+/-0.2 and 95.8+/-5.3mg/g, respectively. The uptake by chylomicrons was
      moderate (31.6+/-5.2%) and high (66.1+/-2.4%), respectively. The bioavailability
      of dexanabinol (37%) was not affected by LCT solution, whereas administration of
      PRS-211,220 in LCT improved the absolute oral bioavailability three-fold (from 13
      to 35%) in comparison to the lipid-free formulation. The intestinal lymphatic
      transport of dexanabinol and PRS-211,220 was 7.5+/-0.8 and 60.7+/-6.8% of the
      absorbed dose, respectively. In conclusion, despite structural similarity and
      similar lipophilicity, dexanabinol and PRS-211,220 exhibited a very diverse
      pattern of oral absorption, and the lymphatic system played quite a different
      role in the oral bioavailability of these molecules. The low lymphatic transport
      of dexanabinol is likely driven by relatively lower affinity to chylomicrons and
      lower LCT solubility.

PMID- 17560097
TI  - [A psychomotor delay in an 18-month-old infant].

PMID- 17560098
TI  - Non-alcoholic fatty liver disease (NAFLD) and cardiovascular disease: an open
      question.
AB  - AIMS: To review available data concerning the basic science and epidemiological
      clinical evidence for an association of NAFLD and cardiovascular disease. DATA
      SYNTHESIS: Non-alcoholic fatty liver disease (NAFLD) defines alcohol-like hepatic
      histological lesions seen in the non-alcoholic, insulin resistant patient
      representing the hepatic counterpart of the metabolic syndrome. Along with
      insulin resistance, additional genetic, endocrine and vascular changes together
      with environmental stimuli--which are also involved in the pathogenesis of
      atherosclerosis--play a prominent role in the development and progression of
      NAFLD. Clinical and epidemiological studies seem to indicate that NAFLD is
      associated with an increased risk for cardiovascular disease but further studies
      are needed to confirm the available data. The mainstay of NAFLD treatment is
      based on the correction of the same metabolic changes that predispose to
      atherosclerosis. CONCLUSIONS: Non-invasive evaluation of risk for cardiovascular
      events is recommended in all individuals presenting with NAFLD and conversely,
      the presence of NAFLD should always be looked for in subjects with features
      belonging to the metabolic syndrome. Further studies are needed on the mechanisms
      linking fatty liver and vascular diseases.

PMID- 17560099
TI  - Solubility-modulated monolithic osmotic pump tablet for atenolol delivery.
AB  - A method for the preparation of monolithic osmotic pump tablet was obtained by
      modulating atenolol solubility with acid. Tartaric acid was used as solubility
      promoter, sodium chloride as osmotic agent and polyvinyl pyrrolidone as retardant
      agent. Ethyl cellulose was employed as semipermeable membrane containing
      polyethylene glycol 400 as plasticizer. The formulation of atenolol monolithic
      osmotic pump tablet was optimized by orthogonal design and evaluated by
      similarity factor (f(2)). The optimal monolithic osmotic pump tablet was found to
      be able to deliver atenolol at the rate of approximate zero-order up to 24h,
      independent of release media and agitation rate. The approach of solubility
      modulated by acid-alkali reaction might be used for the preparation of osmotic
      pump tablet of other poorly water-soluble drugs with alkaline or acid groups.

PMID- 17560100
TI  - Proline prodrug of melphalan, prophalan-L, demonstrates high therapeutic index in
      a murine melanoma model.
AB  - The therapeutic efficacy of prophalan-L, the L-proline prodrug of melphalan that
      demonstrated prolidase-dependent bioactivation to melphalan, was examined in vivo
      in a mouse melanoma model. Prophalan-L exhibited 2- to 2.5-fold higher hydrolytic
      and cytotoxic activity than prophalan-D, the D-analog, in B16-F10 murine melanoma
      cells in vitro. Prophalan-L cytotoxicity in B16-F10 cells was lower (GI50=221
      microM) than that of melphalan (GI50=173 microM). The tumor growth profiles in
      C57BL/6J mice injected with B16-F10 cells and treated with melphalan (5.5
      microg/g i.p.) and equimolar concentrations of the prodrugs demonstrated
      significant difference between the control (buffered saline) and melphalan or
      prophalan-L but no significant difference between control and prophalan-D or
      between melphalan and prophalan-L. Prophalan-L was significantly less toxic than
      melphalan, while no significant difference was observed in toxicity, measured as
      percent weight loss, between the prodrugs and saline control. Tumor reduction
      efficacy at high doses (12 microg/g i.p.) was similar for melphalan and prophalan
      L; however, fatal toxicity was associated with melphalan while prophalan-L
      exhibited significantly lower systemic toxicity. An excellent correlation between
      GI50 and tumor reduction efficacy was observed for the tested drugs (r2=0.95).
      Prophalan-L thus demonstrates higher therapeutic index than melphalan in the
      murine melanoma model.

PMID- 17560101
TI  - Improved sensitivity and stability of amperometric enzyme microbiosensors by
      covalent attachment to gold electrodes.
AB  - Covalent attachment of glucose oxidase to a pre-activated 16-mercaptohexadecanoic
      acid at a gold ultramicroelectrode surface improves sensitivity, stability, and
      reproducibility of enzyme-based amperometric microbiosensors. Self-assembled
      monolayers of the N-hydroxysuccinimide ester of 16-mercaptohexandecanoic acid
      (NHS-MHA) at gold electrodes enable spontaneous covalent linking of glucose
      oxidase to the gold surface of ultramicroelectrodes. By self-assembling NHS-MHA
      for 30 min, approximately 93% of the electrode surface is covered, thereby
      maximizing both the number of attachment sites for glucose oxidase, and
      sufficient diffusion of hydrogen peroxide to the gold electrode. The glucose
      oxidase reaction with NHS-MHA was optimized at pH of 6.5, and at a temperature of
      43 degrees C, resulting in a surface concentration of 6.8+/-0.6 x 10(11)
      enzymemoleculescm(-2). Thus obtained amperometric microbiosensors were calibrated
      in the range of 1-10mM providing excellent correlation with the theoretical
      prediction of the microbiosensor response. The reported sensitivity of these
      microbiosensors documents an improvement by one order of magnitude compared to
      other approaches for covalent enzyme attachment. This is attributed to the NHS
      MHA layer spacing the enzymatic recognition interface further from the electrode
      surface, thereby minimizing quenching of the enzyme activity.

PMID- 17560102
TI  - Carbon nanotube/polysulfone screen-printed electrochemical immunosensor.
AB  - The simple and efficient method for preparing sensitive carbon
      nanotube/polysulfone/RIgG immunocomposite is described. The membrane of the
      modified disposable screen-printed electrochemical immunosensor is based on phase
      inversion method. Carbon nanotube/polysulfone membrane acts both as reservoir of
      immunological material and transducer while offering high surface area, high
      toughness and mechanical flexibility. The comparison with
      graphite/polysulfone/RIgG immunosensors shows a much higher sensitivity for those
      prepared with carbon nanotubes coupled with polysulfone (PSf). The membrane was
      characterized by scanning electron microscopy/energy dispersive X-ray analysis
      (SEM/EDX), laser profilometer and by atomic force microscopy (AFM). The purity of
      the materials was evaluated by thermogravimetric analysis (TGA). The roughness
      value is doubled when MWCNTs are used instead of graphite into the PSf membranes
      and the incorporation of antibodies enhances the dispersion of the carbon with
      the polymeric membrane reducing the roughness in all cases. This biosensor was
      based on the competitive assay between free and labelled anti-RIgG for the
      available binding sites of immobilized rabbit IgG (RIgG). The RIgG was
      incorporated into the polysulfone membrane by a phase inversion method. Horse
      radish peroxidase (HRP) enzyme was used as label and hydroquinone as mediator.
      The detection limit for competitive assay was determined to be 1.66 microg/ml.
      the linear range of anti-RIgG from 2 to 5 microg/ml and the C(50) was found at
      3.56 microg/ml. The sensitivity is five times higher for MWCNT than for graphite
      electrodes, showing lower unspecific adsorption.

PMID- 17560103
TI  - Current status of minimal access surgery for gastric cancer.
AB  - BACKGROUND: The aim was to conduct a systematic review of the literature on the
      subject of laparoscopic gastrectomy (LG) and determine the relative merits of
      laparoscopic (LG) and open gastrectomy (OG) for gastric carcinoma. MATERIAL AND
      METHODS: A search of the Medline, Embase, Science Citation Index, Current
      Contents and PubMed databases identified individual retrospective and prospective
      series on LG (proximal, distal and total). Furthermore, all clinical trials that
      compared LG and OG published in the English language between January 1990 and the
      end of December 2006 were also identified. A large number of outcome variables
      were analysed for individual series and comparative trials between LG and OG and
      results discussed and tabulated. RESULTS: The majority of the literature is
      published from Japan showing both oncological adequacy and safety of LG. The
      majority of early series and comparative studies have utilized laparoscopic
      resection for early and distal gastric cancer. However, with increasing advanced
      laparoscopic experience, advancement in digital technology and improvement in
      instrumentation, more advanced gastric cancers and more extensive procedures such
      as laparoscopic-assisted total gastrectomy and laparoscopy-assisted D2 dissection
      are becoming more common. To date lymph node harvesting, resection margins and
      complication rates seem to be equivalent to open procedures. Furthermore, the
      earlier fears of port-site metastases have not been borne out. CONCLUSIONS: The
      available data suggests that LG seems to be associated with quicker return of
      gastrointestinal function, faster ambulation, earlier discharge from hospital,
      and comparable complications and recurrence rate to OG. However, the operating
      time for LG remains significantly longer compared to its open counterpart,
      although with experience it is achieving parity with OG. However, the majority of
      the comparative trials (if not all) probably do not have the power to detect
      differences in the outcome. As far as the RCT's (LG vs. OG) are concerned, the
      numbers of patients in such trials are small and the majority of patients were
      operated upon for early distal gastric cancer and, therefore, any meaningful
      conclusions regarding the advantages or disadvantages of LG for both the ECGs and
      extensive and advanced gastric tumours are difficult to justify.

PMID- 17560104
TI  - Human serum albumin binding assay based on displacement of a non selective
      fluorescent inhibitor.
AB  - In this paper, we describe a fluorescent antibacterial analog, 6, with utility as
      a competition probe to determine affinities of other antibacterial analogs for
      human serum albumin (HSA). Analog 6 bound to HSA with an affinity of 400+/-100 nM
      and the fluorescence was environmentally sensitive. With 370 nm excitation,
      environmental sensitivity was indicated by a quenching of the 530 nm emission
      when the probe bound to HSA. Displacement of dansylsarcosine from HSA by 6
      indicated it competed with compounds that bound at site II (ibuprofen binding
      site) on HSA. Analog 6 also shifted the NMR peaks of an HSA bound oleic acid
      molecule that itself was affected by compounds that bound at site II. In addition
      to binding at site II, 6 interacted at site I (warfarin binding site) as
      indicated by displacement of dansylamide and the shifting of NMR peaks of an HSA
      bound oleic acid molecule affected by warfarin site binding. Additional evidence
      for multiple site interaction was discovered when a percentage of 6 could be
      displaced by either ibuprofen or phenylbutazone. A competition assay was
      established using 6 to determine relative affinities of other antibacterial
      inhibitors for HSA.

PMID- 17560105
TI  - Bicyclo[2.2.2]octanes: close structural mimics of the nuclear receptor-binding
      motif of steroid receptor coactivators.
AB  - Nuclear hormone receptor (NR) function relies on association of agonist-bound
      receptors with steroid receptor coactivator (SRC) proteins through a small
      pentapeptide motif (LXXLL) of the SRC that binds to a hydrophobic groove on the
      NR. We have synthesized a series of bicyclo[2.2.2]octanes that are close
      structural mimics of the two key leucine residues of this SRC sequence as bound
      in the hydrophobic groove of the estrogen receptor. These bicyclic systems block
      the NR-SRC interaction with modest potency.

PMID- 17560106
TI  - Synthesis of 4-phenoxybenzamide adenine dinucleotide as NAD analogue with
      inhibitory activity against enoyl-ACP reductase (InhA) of Mycobacterium
      tuberculosis.
AB  - The chemical synthesis of 4-phenoxybenzamide adenine dinucleotide (3), a NAD
      analogue which mimics isoniazid-NAD adduct and inhibits Mycobacterium
      tuberculosis NAD-dependent enoyl-ACP reductase (InhA), is reported. The 4-phenoxy
      benzamide riboside (1) has been prepared as a key intermediate, converted into
      its 5'-mononucleotide (2), and coupled with AMP imidazolide to give the desired
      NAD analogue 3. It inhibits InhA with IC50 = 27 microM.

PMID- 17560107
TI  - Dual bioactivity of resveratrol fatty alcohols: differentiation of neural stem
      cells and modulation of neuroinflammation.
AB  - The synthesis of resveratrol fatty alcohols (RFAs), a new class of small
      molecules presenting strong potential for the treatment of neurological diseases,
      is described. RFAs, hybrid compounds combining the resveratrol nucleus and omega
      alkanol side chains, are able to modulate neuroinflammation and to induce
      differentiation of neural stem cells into mature neurons. Acting on
      neuroprotection and neuroregeneration, RFAs represent an innovative approach for
      the treatment or cure of neuropathies.

PMID- 17560108
TI  - New modifications to the area of pyrazole-naphthyl urea based p38 MAP kinase
      inhibitors that bind to the adenine/ATP site.
AB  - Discovery of the pyrazole-naphthyl urea class of p38 MAP kinase inhibitors
      typified by the clinical candidate BIRB 796 has encouraged further exploration of
      this particular scaffold. Modification to the part of the inhibitor that occupies
      the adenine/ATP binding site has resulted in a new way to obtain potent
      inhibitors that possess favorable in vitro and in vivo properties.

PMID- 17560109
TI  - Synthesis and pharmacological testing of polyaminoquinolines as blockers of the
      apamin-sensitive Ca2+-activated K+ channel (SK(Ca)).
AB  - The synthesis and pharmacological testing of a series of non-peptidic blockers of
      the SK(Ca) (SK-3) channel is described. Target compounds were designed to mimic
      the spatial relationships of selected key residues in the energy-minimised
      structure of the octadecapeptide apamin, which are a highly potent blocker of
      this channel. Structures consist of a central unit, either a fumaric acid or an
      aromatic ring, to which are attached two alkylguanidine or two to four
      alkylaminoquinoline substituents. Potency was tested by the ability to inhibit
      the SK(Ca) channel-mediated after-hyperpolarization (AHP) in cultured rat
      sympathetic neurones. It was found that bis-aminoquinoline derivatives are
      significantly more potent as channel blockers than are the corresponding
      guanidines. This adds to the earlier evidence that delocalisation of positive
      charge through the more extensive aminoquinolinium ring system is important for
      effective channel binding. It was also found that an increase in activity can be
      gained by the addition of a third aminoquinoline residue to give non-quaternized
      amines which have submicromolar potencies (IC(50)=0.13-0.36 microM). Extension to
      four aminoquinoline residues increased the potency to IC(50)=93 nM.

PMID- 17560111
TI  - Design, synthesis, and biological evaluation of LNA nucleosides as adenosine A3
      receptor ligands.
AB  - We have prepared a series of adenosine analogs based on the bicyclo[2.2.1]heptane
      scaffold of locked nucleic acid (LNA) and tested them for both agonist and
      antagonist activity at the adenosine A(3) receptor. The design of these
      derivatives was based on the known A(3) agonist IB-MECA and related compounds.
      Modifications thus include the 5'-uronamides and N(6)-(3-iodobenzyl) derivatives.
      In this way we have prepared analogs of known A(3) agonists with the sugar ring
      restricted in an N-conformation. For comparison we have also prepared 2'-O-methyl
      derivatives of IB-MECA. The LNA nucleosides showed no agonist activity but some
      of them are potent antagonists. The 2'-O-methyl derivative of IB-MECA is an
      agonist with similar potency as the parent compound.

PMID- 17560110
TI  - 3-Hydroxy-1,5-dihydro-pyrrol-2-one derivatives as advanced inhibitors of HIV
      integrase.
AB  - The two-metal binding model we previously reported as an inhibition mechanism of
      HIV integrase (HIV IN) produced a new direction in modification of 2-hydroxy-3
      heteroaryl acrylic acid inhibitors (HHAAs). Here we present a novel series of HIV
      IN inhibitors having a 3-hydroxy-1,5-dihydro-pyrrol-2-one moiety (HDPO) as an
      advanced analog of HHAAs. This cyclic modification of the chelating region of
      HHAA produces a favorable configuration to coordinate two-metal ions in HIV IN,
      which consequently gave improvements in not only enzymatic assay but also
      antiviral cell based assay in many cases.

PMID- 17560112
TI  - Antiproliferative, low-calcemic, fluorinated sulfone analogs of 1alpha,25
      dihydroxyvitamin D3: chemical synthesis and biological evaluation.
AB  - Novel fluorinated sulfone analogs of the hormone 1alpha,25-dihydroxyvitamin D(3)
      have been designed and synthesized in order to study the biological effects of
      fluorine incorporation at the terminus of the C,D-ring side chain. Although
      biologically active 26,27-hexafluorinated 1alpha,25-dihydroxyvitamin D(3) analogs
      have been synthesized previously, this investigation reports the first successful
      fluorinated series in which trifluoromethyl sulfone analogs present a favorable
      biological profile. This study shows that two new analogs featuring incorporation
      of a synthetically simple single trifluoromethyl sulfone group have significantly
      increased antiproliferative activity while causing desirably low in vivo
      calciuria relative to that of calcitriol. Incorporation of additional fluorines,
      as in a perfluorobutyl analog, results in a loss of antiproliferative activity.

PMID- 17560113
TI  - Habit learning dissociation in rats with lesions to the vermis and the
      interpositus of the cerebellum.
AB  - After cerebellar tumors resection, patients show motor skill learning impairments
      but also cognitive deficits. However, their exact origins remain controversial.
      Using a rat model of cerebellar injury, we assessed the involvement of two
      structures often damaged during resection (vermis and interpositus nuclei) on
      habits development. During extended training of an instrumental task, rats
      develop response routines that are no longer voluntary or goal-directed but habit
      based, evidenced by their insensitivity to changes in the value of the reward.
      Here we showed that, in contrast to sham or vermis lesioned rats, discrete
      lesions to interpositus nuclei prevented rats from developing habits with
      overtraining, without motor difficulties, nor alteration of the instrumental task
      acquisition. Our results suggest that the role of the cerebellum can be extended
      from motor skill learning to cognitive routines learning. Similar habit
      impairment could possibly account for some of the long-term outcome difficulties
      observed in cerebellar-damaged patients.

PMID- 17560114
TI  - Pentatricopeptide repeat proteins and their emerging roles in plants.
AB  - Several protein families with tandem repeat motifs play a very important role in
      plant development and defense. The pentatricopeptide repeat (PPR) protein family,
      one of the largest families, is the most perplexing one in plants. PPR proteins
      have been implicated in many crucial functions broadly involving organelle
      biogenesis and plant development. PPR motifs are degenerate motifs, each with 35
      amino-acid sequences and are present in tandem arrays of 2-27 repeats per
      protein. Although PPR proteins are found in other eukaryotes, their large number
      is probably required in plants to meet the specific needs of organellar gene
      expression. The repeats of PPR proteins form a superhelical structure to bind a
      specific ligand, probably a single-stranded RNA molecule, and modulate its
      expression. Functional studies on different PPR proteins have revealed their role
      in organellar RNA processing, fertility restoration in CMS plants, embryogenesis,
      and plant development. Functional genomic techniques can help identify the
      diverse roles of the PPR family of proteins in nucleus-organelle interaction and
      in plant development.

PMID- 17560115
TI  - Retroesophageal right subclavian artery (lusoria) as origin of traumatic aortic
      rupture.
AB  - A retroesophageal right subclavian artery (lusoria) is unusual for the surgeon,
      yet common regarding pathological findings (0.5-2%). Complications arising from
      it are rare (dysphagia). We report a case of traumatic descending aortic tear
      originating from a lusoria. The patient had experienced chest trauma due to a
      skiing accident. CT scan revealed an intramural haematoma of the proximal
      descending aorta. As a coincidence finding, a retroesophageal right subclavian
      artery was diagnosed. The patient was first treated conservatively. After an
      initial period--of stable patient conditions--repeated CT scan revealed a
      haematoma enlargement and surgery was scheduled: A localized aortic tear was
      suspected through CT scan, yet no aortic tear or flap was visible. During a two
      staged surgical procedure, transpositioning of the lusoria into the right common
      carotid artery was performed, followed by replacement of the distal aortic arch
      during a second session using a single-branched Dacron tube graft. The left
      subclavian artery was then reinserted into the side-branched graft after reuptake
      of extracorporeal circulation. Extracorporeal circulation was applied via the
      femoral vessels and circulatory arrest in combination with deep hypothermia.
      After surgery, the patient was stable, having no signs of neurocognitive
      dysfunction or dysphagia.

PMID- 17560116
TI  - Thyroid hormone attenuates cardiac remodeling and improves hemodynamics early
      after acute myocardial infarction in rats.
AB  - OBJECTIVE: Cardiac remodeling of viable myocardium occurs after acute myocardial
      infarction (AMI) and further contributes to cardiac dysfunction. The present
      study explored whether thyroid hormone (TH) administered shortly after AMI in
      rats can attenuate cardiac remodeling and improve cardiac function. TH regulates
      important structural and regulatory proteins in the myocardium including myosin
      isoform expression and calcium cycling proteins. METHODS: AMI was induced in
      Wistar male rats by ligating left coronary artery (AMI, n=10), while sham
      operated rats were used as controls (SHAM, n=10). Animals with acute myocardial
      infarction were also treated with 0.05% thyroid powder in food (AMI-THYR, n=10).
      Within 2 weeks, cardiac function was impaired as assessed by echocardiography and
      under isometric conditions in Langendorff preparations. RESULTS: Ejection
      fraction (EF%) was 71.5 (SEM, 2.7) in SHAM versus 30.0 (2.0) in AMI, P<0.05.
      +dp/dt was 3886 (566) in SHAM versus 2266 (206) in AMI hearts, P<0.05 and -dp/dt
      was 1860 (46) in SHAM versus 1633 (120) in AMI hearts, P=ns. Such changes were
      associated with alterations in myosin isoform expression in the non-infarcted
      area; AMI hearts expressed 34% alpha-MHC and 66% beta-MHC versus 52% alpha-MHC
      and 48% beta-MHC in SHAM, P<0.05, while the expression of SERCA and phospholamban
      (PLB) remained unchanged. Furthermore, a mismatch of left ventricular size and
      cardiac mass (2*Posterior Wall thickness/LVIDd was decreased) was observed. After
      TH treatment, AMI-THYR hearts expressed 71% alpha-MHC and 29% beta-MHC, P<0.05
      versus SHAM and AMI and the ratio of SERCA/PLB was increased by 2.0-fold, P<0.05
      versus SHAM and AMI. These changes corresponded to a marked improvement in
      cardiac function; EF% was raised to 45.8 (1.7), P<0.05 versus AMI while +dp/dt
      and -dp/dt were 3800 (435) and 2600 (200), respectively, in AMI-THYR hearts,
      P<0.05 versus AMI. The ratio of 2*Posterior Wall thickness/LVIDd was normalized.
      CONCLUSIONS: Thyroid hormone administration early after infarction attenuates
      cardiac remodeling and significantly improves myocardial performance.

PMID- 17560117
TI  - Targeting the conversion of ceramide to sphingosine 1-phosphate as a novel
      strategy for cancer therapy.
AB  - Sphingolipids not only function as structural components of cell membranes but
      also act as signaling molecules to regulate fundamental cellular responses, such
      as cell death and differentiation, proliferation and certain types of
      inflammation. Particularly the cellular balance between ceramide and sphingosine
      1-phosphate seems to be crucial for a cell's decision to either undergo apoptosis
      or proliferate, two events which are implicated in tumor development and growth.
      Whereas ceramide possesses proapoptotic capacity in many cell types, sphingosine
      1-phosphate acts as a counterplayer able to induce cell proliferation and protect
      cells from undergoing apoptosis. Therefore, tipping the balance in favour of
      ceramide production, i.e. by inhibiting ceramidase or sphingosine kinase
      activities has potential to support its proapoptotic action and hence represents
      a promising rational approach to effective cancer therapy. This review highlights
      most recent data on the regulation of cellular sphingolipid formation and their
      potential implication in tumor development, and provides perspectives for their
      use as targets in molecular intervention therapy.

PMID- 17560118
TI  - TGF-beta(1) gene polymorphism in psoriasis vulgaris.
AB  - Overexpression of TGF-beta(1) has been implicated in the pathology of many
      inflammatory diseases, including psoriasis. This study was performed to
      investigate the association between TGF-beta(1) single nucleotide polymorphism
      and susceptibility for psoriasis vulgaris. DNA from 78 patients with psoriasis
      vulgaris and 74 healthy volunteers was investigated. Polymorphism of TGF-beta(1)
      gene in codon 10 (T/C) and codon 25 (G/C) was evaluated by PCR-SSP and the
      results were compared between group of psoriatic patients, divided into early
      onset of psoriasis (type I) and late onset of psoriasis (type II) subgroups, and
      control healthy subjects. Frequencies in genotypes were similar between patients
      and control group (p >0.7), but between type I and type II psoriasis patients
      highly significant difference was found (p <0.0003). Higher frequency of CC/GG
      (intermediate producer) and TC/GG (high producer) was noted in the type I group,
      but the second high producer genotype (TT/GG) was more common in type II group.
      Also between type II psoriasis patients and healthy controls statistically
      significant difference was found (p <0.000001). In analyzing frequencies of
      carriage and alleles no significant differences were found. TGF-beta(1) gene
      polymorphism in codon 10 and 25 is not associated with susceptibility to
      psoriasis vulgaris, but may be important for the type of the disease.

PMID- 17560119
TI  - The combination of electron capture dissociation and fixed charge derivatization
      increases sequence coverage for O-glycosylated and O-phosphorylated peptides.
AB  - Electron capture dissociation (ECD) has become an alternative method to collision
      activated dissociation (CAD) to avoid gas-phase cleavage of post-translational
      modifications carried by side chains from the peptide backbone. Nonetheless, as
      illustrated herein by the study of O-glycosylated and O-phosphorylated peptides,
      the extent of ECD fragmentations may be insufficient to cover the entire peptide
      sequence and to localize accurately these modifications. The present work
      demonstrates that the derivatization of peptides at their N-terminus by a
      phosphonium group improves dramatically and systematically the sequence coverage
      deduced from the ECD spectrum for both O-glycosylated and O-phosphorylated
      peptides compared with their native counterparts. The exclusive presence of N
      terminal fragments (c-type ions) in the ECD spectra of doubly charged molecular
      cations simplifies peptide sequence interpretation. Thus, the combination of ECD
      and fixed charge derivatization appears as an efficient analytical tool for the
      extensive sequencing of peptides bearing labile groups.

PMID- 17560121
TI  - Molecular mechanisms involved in T cell receptor triggering.
AB  - Despite intensive investigation we still do not understand how the T cell antigen
      receptor (TCR) tranduces signals across the plasma membrane, a process referred
      to as TCR triggering. Three basic mechanisms have been proposed, involving
      aggregation, conformational change, or segregation of the TCR upon binding pMHC
      ligand. Given the low density of pMHC ligand it remains doubtful that TCR
      aggregation initiates triggering, although it is likely to enhance subsequent
      signalling. Structural studies to date have not provided definitive evidence for
      or against a conformational change mechanism, but they have ruled out certain
      types of conformational change. Size-induced segregation of the bound TCR from
      inhibitory membrane tyrosine phosphatases seems to be required, but is probably
      not the only mechanism. Current evidence suggests that TCR triggering is
      initiated by a combination of segregation and conformational change, with
      subsequent aggregation contributing to amplification of the signal.

PMID- 17560120
TI  - TCR recognition of peptide/MHC class II complexes and superantigens.
AB  - Major histocompatibility complex (MHC) class II molecules display peptides to the
      T cell receptor (TCR). The ability of the TCR to discriminate foreign from self
      peptides presented by MHC molecules is a requirement of an effective adaptive
      immune response. Dysregulation of this molecular recognition event often leads to
      a disease state. Recently, a number of structural studies have provided
      significant insight into several such dysregulated interactions between
      peptide/MHC complexes and TCR molecules. These include TCR recognition of self
      peptides, which results in autoimmune reactions, and of mutant self-peptides,
      common in the immunosurveillance of tumors, as well as the engagement of TCRs by
      superantigens, a family of bacterial toxins responsible for toxic shock syndrome.

PMID- 17560122
TI  - Microglia can be induced by IFN-gamma or IL-4 to express neural or dendritic-like
      markers.
AB  - Microglia are resident cells in the central nervous system (CNS), of
      hematopoietic origin with a high plasticity. In this study, we examined whether
      adaptive immune system, involving in CNS maintenance and repair, can induce
      microglia to express markers of neural cells. We show that long exposure (above
      10 days) of microglia to low doses (10 ng/ml) of the 'proinflammatory' T-cell
      derived cytokine, IFN-gamma, induced them to express neuronal markers including
      gamma-aminobutyric acid (GABA) and glutamic acid decarboxylase (GAD-67). In
      contrast, exposure of microglia to low doses (10 ng/ml) of the 'anti
      inflammatory' T-cell derived cytokine, IL-4, induced the expression of
      oligodendrocyte markers and dendritic cell (DC) marker, CD11c. The microglial
      origin of the neural-like cells was confirmed using microglia from transgenic
      mice expressing GFP under promoter of the chemokine fractalkine receptor
      CX(3)CR1, and diphtheria toxin receptor, under CD11c promoter. This study
      emphasizes that microglial plasticity includes their ability to give rise to
      neural-like cells and shows that cytokines produced by the adaptive immune system
      are involved in these processes.

PMID- 17560123
TI  - The influence of stress on the menstrual cycle among newly incarcerated women.
AB  - OBJECTIVE: We sought to estimate the association of stressful life events on
      menstrual function in incarcerated women. METHODS: Project CONNECT is a study of
      reproductive health needs of incarcerated women conducted between June 2002 and
      December 2003. This analysis examines menstrual function in 446 women from this
      cohort who were under the age of 45. Regularity was defined as menses between 26
      and 35 days long. Amenorrhea was defined as > or =90 days since last
      menstruation. Measures included stressful experiences and deprivation (e.g.,
      physical or sexual abuse, stressful living conditions, exchanging sex for drugs
      or money, or having had an incarcerated parent). RESULTS: Menstrual dysfunction
      was common in this population. Nine percent reported amenorrhea, and 33% reported
      menstrual irregularity. A number of stressors were associated with menstrual
      irregularity, including having a parent with history of alcohol or drug problems
      (relative risk [RR] = 1.34; 95% confidence interval [CI], 1.00-1.80), childhood
      physical or sexual abuse (RR = 1.48; 95% CI, 1.03-2.13), or any sexual abuse (RR
      = 1.49; 95% CI, 1.03-2.14) after adjusting for age, race/ethnicity, smoking
      status, and recent drug use. These effects were attenuated somewhat when
      excluding women who had reported any hormonal contraceptive use in the past 3
      months. CONCLUSION: Incarcerated women have high rates of amenorrhea and
      menstrual irregularity and the prevalence may be associated with certain
      stresses. Further research on the causes and consequences of menstrual
      dysfunction in this underserved population is needed.

PMID- 17560124
TI  - Health, mental health, substance use, and service utilization among rural and
      urban incarcerated women.
AB  - Incarcerated women commonly report health, mental health, and substance use
      problems, yet there is limited research on service utilization before
      incarceration, particularly among women from urban and rural areas. This study
      includes a stratified random sample of 100 rural and urban incarcerated women to
      profile the health, mental health, substance use, and service utilization;
      examine the relationship between the number of self-reported problems and service
      utilization; and examine self-reported health and mental health problems in
      prison as associated with preincarceration health-related problems and community
      service utilization. Study findings suggest that health and mental health
      problems and substance use do not differ significantly among rural and urban
      women prisoners. However, there are differences in service utilization --
      particularly behavioral health services including mental health and substance
      abuse services; urban women report more service utilization. In addition, rural
      women who reported using needed community services before prison also reported
      fewer health problems in prison. Implications for correctional and community
      treatment opportunities in rural and urban areas are discussed.

PMID- 17560125
TI  - High-density surface EMG study on the time course of central nervous and
      peripheral neuromuscular changes during 8 weeks of bed rest with or without
      resistive vibration exercise.
AB  - The aim of the present study was to assess the time course and the origin of
      adaptations in neuromuscular function as a consequence of prolonged bed rest with
      or without countermeasure. Twenty healthy males volunteered to participate in the
      present study and were randomly assigned to either an inactive control group
      (Ctrl) or to a resistive vibration exercise (RVE) group. Prior to, and seven
      times during bed rest, we recorded high-density surface electromyogram (sEMG)
      signals from the vastus lateralis muscle during isometric knee extension exercise
      at a range of contraction intensities (5-100% of maximal voluntary isometric
      torque). The high-density sEMG signals were analyzed for amplitude (root mean
      square, RMS), frequency content (median frequency, F(med)) and muscle fiber
      conduction velocity (MFCV) in an attempt to describe bed rest-induced changes in
      neural activation properties at the levels of the motor control and muscle
      fibers. Without countermeasures, bed rest resulted in a significant progressive
      decline in maximal isometric knee extension strength, whereas RMS remained
      unaltered throughout the bed rest period. In line with observed muscle atrophy,
      both F(med) and MFCV declined during bed rest. RVE training during bed rest
      resulted in maintained maximal isometric knee extension strength, and a strong
      increase ( approximately 30%) in maximal EMG amplitude, from 10 days of bed rest
      on. Exclusion of other factors led to the conclusion that the RVE training
      increased motor unit firing rates as a consequence of an increased excitability
      of motor neurons. An increased firing rate might have been essential under
      training sessions, but it did not affect isometric voluntary torque capacity.

PMID- 17560126
TI  - A component based noise correction method (CompCor) for BOLD and perfusion based
      fMRI.
AB  - A component based method (CompCor) for the reduction of noise in both blood
      oxygenation level-dependent (BOLD) and perfusion-based functional magnetic
      resonance imaging (fMRI) data is presented. In the proposed method, significant
      principal components are derived from noise regions-of-interest (ROI) in which
      the time series data are unlikely to be modulated by neural activity. These
      components are then included as nuisance parameters within general linear models
      for BOLD and perfusion-based fMRI time series data. Two approaches for the
      determination of the noise ROI are considered. The first method uses high
      resolution anatomical data to define a region of interest composed primarily of
      white matter and cerebrospinal fluid, while the second method defines a region
      based upon the temporal standard deviation of the time series data. With the
      application of CompCor, the temporal standard deviation of resting-state
      perfusion and BOLD data in gray matter regions was significantly reduced as
      compared to either no correction or the application of a previously described
      retrospective image based correction scheme (RETROICOR). For both functional
      perfusion and BOLD data, the application of CompCor significantly increased the
      number of activated voxels as compared to no correction. In addition, for
      functional BOLD data, there were significantly more activated voxels detected
      with CompCor as compared to RETROICOR. In comparison to RETROICOR, CompCor has
      the advantage of not requiring external monitoring of physiological fluctuations.

PMID- 17560127
TI  - Commentary on Devlin and Poldrack.

PMID- 17560128
TI  - Cortical lateralization of bilateral symmetric chin movements and clinical
      relevance in tumor patients--a high field BOLD-FMRI study.
AB  - Although unilateral lesion studies concerning the opercular part of primary motor
      cortex report clinically severe motor deficits (e.g. anarthria, masticatory
      paralysis), functional lateralization of this area has not yet been addressed in
      neuroimaging studies. Using BOLD-FMRI, this study provides the first quantitative
      evaluation of a possible cortical lateralization of symmetric chin movements
      (rhythmic contraction of masticatory muscles) in right-handed healthy subjects
      and presurgical patients suffering tumorous lesions in the opercular primary
      motor cortex. Data were analyzed according to "activation volume" and "activation
      intensity". At group level, results showed a strong left-hemispheric dominance
      for chin movements in the group of healthy subjects. In contrast, patients
      indicated dominance of the healthy hemisphere. Here, a clinically relevant
      dissociation was found between "activation volume" and "activation intensity":
      Although "activation volume" may be clearly lateralized to the healthy
      hemisphere, "activation intensity" may indicate residual functionally important
      tissue close to the pathological tissue. In these cases, consideration of BOLD
      FMRI maps with the exclusive focus on "activation volume" may lead to erroneous
      presurgical conclusions. We conclude that comprehensive analyses of presurgical
      fMRI data may help to avoid sustained postoperative motor deficits and dysarthria
      in patients with lesions in the opercular part of primary motor cortex.

PMID- 17560129
TI  - Identifying mutual information transfer in the brain with differential-algebraic
      modeling: Evidence for fast oscillatory coupling between cortical somatosensory
      areas 3b and 1.
AB  - Understanding information transfer in the brain is a major challenge in today's
      neurosciences. Commonly, information transfer between brain areas is analyzed
      with the help of correlation measures for electrophysiological data. However,
      such approaches cannot distinguish between mutual coupling and other mechanisms
      of creating correlations between responses, such as common input from other
      sources. Functional coupling is mandatory for information transfer. Here we
      propose to analyze coupling between active brain areas with the help of models
      described by a system of differential-algebraic equations. Comparing models with
      various degrees of coupling, we show that mutual information transfer can be
      distinguished from one-way information transfer for activated cortical areas
      estimated by source localization techniques. We exemplify the technique with fast
      oscillatory activity found in both cortical areas 3b and 1 after peripheral nerve
      stimulation.

PMID- 17560130
TI  - Reducing the unwanted draining vein BOLD contribution in fMRI with statistical
      post-processing methods.
AB  - Recent BOLD fMRI data analysis methods show promise in reducing contributions
      from draining veins. The phase regressor method developed by [Menon, R.S., 2002.
      Post-acquisition suppression of large-vessel BOLD signals in high-resolution
      fMRI. Magn. Reson. Med., 47, 1-9] creates phase and magnitude images, regresses
      magnitude as a function of phase, and subtracts phase-estimated magnitudes from
      the observed magnitudes. The corrected magnitude images are used to compute
      cortical activations. The complex constant phase method, developed by [Rowe,
      D.B., Logan, B.R., 2004. A complex way to compute fMRI activation. NeuroImage,
      23, 1078-1092], uses complex-valued reconstructed images and a nonlinear
      regressor model to compute magnitude cortical activations assuming temporally
      constant phase. In both methods, the usage of the phase information is claimed to
      bias against voxels with task-related phase changes caused by some draining
      veins. The behavior of the statistical methods in data with several task-related
      magnitude and phase changes is compared. The power of the statistical methods for
      determining voxels with specific task-related magnitude and phase change
      combinations are determined in ideal simulated data. The phase regressor and
      complex constant phase activation determination techniques are examined to
      characterize the responses of the models to select task-related phase and
      magnitude change combinations in representative simulated time series. Possible
      draining veins in human preliminary data are discussed and analyzed with the
      models and the current challenges which prevent these methods from being reliably
      implemented are discussed.

PMID- 17560131
TI  - Phylogeny of coral-inhabiting barnacles (Cirripedia; Thoracica; Pyrgomatidae)
      based on 12S, 16S and 18S rDNA analysis.
AB  - The traditional phylogeny of the coral-inhabiting barnacles, the Pyrgomatidae, is
      based on morphological characteristics, mainly of the hard parts. It has been
      difficult to establish the phylogenetic relationships among Pyrgomatidae because
      of the apparent convergence of morphological characteristics, and due to the use
      of non-cladistic systematics, which emphasize ancestor-descendant relationships
      rather than sister-clade relationships. We used partial sequences of two
      mithochondrial genes, 12S rDNA and 16S rDNA, and a nuclear gene, 18S rDNA, to
      infer the molecular phylogeny of the pyrgomatids. Our phylogenetic results
      allowed us to reject previous classifications of Pyrgomatidae based on
      morphological characteristics. Our results also suggested the possibility of
      paraphyly of the Pyrgomatidae. The hydrocoral barnacle Wanella is not found on
      the same clade as the other pyrgomatids, but rather, with the free-living
      balanids. The basal position of Megatrema and Ceratoconcha is supported. The
      archeaobalanid Armatobalanus is grouped with Cantellius at the base of the Indo
      Pacific pyrgomatines. Fusion of the shell plate and modification of the opercular
      valves are homoplasious features that occurred more than three times on different
      clades. The monophyly of the "Savignium" group, comprising four nominal genera,
      is also not supported, and the different taxa are placed on different clades.

PMID- 17560132
TI  - Pharmacokinetic-pharmacodynamic modeling of diltiazem in spontaneously
      hypertensive rats: a microdialysis study.
AB  - INTRODUCTION: The aim of the present work was to study the applicability of a
      modified E(max) pharmacodynamic model for the pharmacokinetic-pharmacodynamic (PK
      PD) modeling of diltiazem in spontaneously hypertensive rats (SHR) and
      normotensive Wistar Kyoto (WKY) rats. METHODS: A "shunt" microdialysis probe was
      inserted in a carotid artery of anaesthetized SHR and WKY rats for simultaneous
      determination of unbound plasma concentrations of diltiazem and their effects on
      mean arterial pressure (MAP) and heart rate (HR) after the intravenous
      application of 1 and 3 mg kg(-1) of the drug. Correlation between diltiazem
      plasma levels and their cardiovascular effects was established by fitting the
      data to a conventional and modified E(max) model. RESULTS: Volume of distribution
      and clearance of diltiazem was greater in SHR than in WKY animals. A proportional
      increase of area under curve with dose increment was observed in WKY animals but
      not in SHR. A good correlation between plasma unbound concentrations of diltiazem
      and their hypotensive and chronotropic effects was found in both experimental
      groups using both PK-PD models. The application of the modified E(max) model for
      PK-PD modeling of diltiazem allowed a more accurate and precise estimation of PK
      PD parameters than the E(max) equation do. Chronotropic effect of 3 mg kg(-1)
      diltiazem was lower in SHR compared to WKY animals. Initial sensitivity (S(0)) to
      diltiazem chronotropic effect was greater in SHR with regards to WKY animals
      after administration of 1 mg kg(-1). S(0) to diltiazem hypotensive effect was
      greater in SHR with regards to WKY animals after administration of both doses of
      diltiazem. DISCUSSION: Microdialysis sampling is a useful technique for the
      pharmacokinetic study and pharmacokinetic-pharmacodynamic (PK-PD) modeling of
      diltiazem. The modified E(max) model allows an accurate estimation of drug
      sensitivity in conditions when maximal pharmacological response can not be
      attained. Genetic hypertension induced changes in the pharmacokinetic and PK-PD
      behavior of diltiazem suggesting that SHR is an interesting animal model for pre
      clinical evaluation of calcium channel blockers.

PMID- 17560133
TI  - Serial day rapid kindling is an effective tool in screening the anti-epileptic
      properties of topiramate.
AB  - INTRODUCTION: In this study, a serial day rapid kindling protocol was used to
      fully kindle rats in a matter of days. Subsequently, the anticonvulsant profile
      of a relatively new anti-epileptic drug, topiramate, was evaluated in a cross
      over design to further validate this rapid kindling model. METHODS: Rats were
      kindled during three consecutive days, according to the serial day rapid kindling
      protocol. Topiramate was tested at a dose of 100mg/kg, i.p., over the next 2 days
      using a cross-over design. The stability of the kindled state was evaluated in
      all rats during two retest paradigms. During the drug-testing procedure, rats
      received a single i.p. injection of either topiramate or verhicle. Starting 1 h
      later the rats received additional kindling stimulations during which their
      response was measured. RESULTS: Serial day rapid kindling induced a long lasting
      and stable fully kindled state that allowed for the anti-epileptic drug screening
      procedure. Topiramate reduced both the afterdischarge duration and ameliorated
      seizure semiology in the kindled rats. DISCUSSION: Serial day rapid kindling
      provided a tool to rapidly kindle rats in 3 days. Using a cross-over design,
      clear indications on anti-epileptic activity of a given drug can be determined
      using few laboratory animals.

PMID- 17560134
TI  - A study of the prevalence and associations of subchondral bone marrow lesions in
      the knees of healthy, middle-aged women.
AB  - OBJECTIVE: Bone marrow lesions (BMLs) have been shown to be associated with pain
      and progression of knee osteoarthritis (OA) in those with disease. The natural
      history of BMLs in a healthy population and their role in the pathogenesis of OA
      are unknown. The aim of this study was to determine the risk factors for BMLs in
      healthy subjects and the association of BMLs with knee structure. METHODS: One
      hundred and seventy-six healthy, adult women with no history of knee injury, or
      clinical knee OA had magnetic resonance imaging performed on their dominant knee
      to assess BMLs, tibiofemoral cartilage defects, tibial cartilage volume and bone
      area. RESULTS: Thirteen percent of subjects had knee BMLs. The prevalence was
      higher in the medial tibiofemoral compartment. There was a significant positive
      association between BMLs and cartilage defects after adjusting for the potential
      risk factors: age, height, weight and cartilage volume [odds ratio (OR) 1.78 (95%
      confidence interval [CI] 1.12, 2.82), P=0.01]. BML was positively associated with
      tibial plateau bone area in the lateral compartment [OR 1.67 (95% CI 1.02, 2.71),
      P=0.04]. There was no significant association between BMLs and cartilage volume.
      Independent risk factors for BMLs after adjustment were increasing height [OR
      1.18 (95% CI 1.02, 1.36), P=0.02 for lateral compartment] and weight [OR 1.04
      (95% CI 1.01, 1.08), P=0.005 for total knee]. CONCLUSION: These data support that
      BMLs are present in a similar distribution to tibiofemoral knee OA. Their
      presence is associated with risk factors (height and weight) for knee OA, and the
      early structural changes of knee OA in subjects without knee pain and thus no
      clinical disease. Longitudinal studies will clarify whether BMLs relate to the
      pathogenesis of clinical knee OA.

PMID- 17560135
TI  - Comparison of human pulp response to total-etch and self-etch bonding agents.
AB  - OBJECTIVE: To compare the pulp reactions in terms of pulp inflammation, leakage
      involving bacteria and reactionary dentin formation to total-etch adhesive, Prime
      & Bond NT and self-etch adhesive, Xeno III in 2 mm deep class V cavities prepared
      in human teeth. STUDY DESIGN: 2 mm deep class V cavities were prepared on buccal
      surface of 40 human premolars. The teeth were randomly divided into two groups
      based on the application of a total-etch adhesive system, Prime and Bond NT after
      acid etching or a self-etching adhesive system, Xeno III. The teeth were
      extracted after 7 and 30 days and prepared according to routine histological
      techniques. RESULTS: All teeth were asymptomatic. Both the adhesives showed
      moderate to severe inflammatory reactions in few cases initially at seven days,
      but the response was generally minimal at 30 days. Leakage involving bacteria was
      detected in 42.5% of restorations and 40% of the specimens were associated with
      various grades of pulp inflammation. The cavity remaining dentin thickness
      influenced the grade of inflammatory activity. A significant correlation was
      detected between inflammatory cell response and the presence of bacteria. Pulp
      response to self-etching adhesive, Xeno III was minimally different from that of
      the total-etch adhesive, Prime & Bond NT (p < .05). CONCLUSIONS: A self-etching
      adhesive system, Xeno III showed similar pulp response and leakage involving
      bacteria to a total-etch adhesive, Prime & Bond NT. Both adhesives showed an
      acceptable biological compatibility with human pulps at 30 days.

PMID- 17560136
TI  - Lesions of the oral mucosa: an epidemiological study of 23785 Mexican patients.
AB  - This study is a cross-sectional report of oral mucosal lesions in 23785 patients
      more than 15 years of age who requested elective dental care in a dental school.
      Among the patients examined, the general lesion rate was 356.60 lesions per 1000
      patients. Sixty-eight entities were identified, the lesions being more common
      among males. White, red, and ulcerated lesions were seen to predominate,
      associated mostly with chronic irritative causative factors. The prevalence rates
      of individual oral mucosal lesions ranged from 0.55 to 105.36 per 1000 patients
      examined. Age and sex assessment showed some differences in the type and
      presentation rates of the lesions. These and other epidemiological aspects are
      discussed.

PMID- 17560137
TI  - Expression of receptor activator of nuclear factor-kappaB ligand in synovial
      tissue: comparison with degradation of articular cartilage in temporomandibular
      joint disorders.
AB  - OBJECTIVE: The present study was performed to investigate the correlations
      between expression of the receptor activator of nuclear factor-kappaB ligand
      (RANKL) in synovial tissue and the degrees of synovitis, degeneration of
      articular cartilage, and adhesions in patients with internal derangement (ID) of
      the temporomandibular joint (TMJ). STUDY DESIGN: Expression of RANKL, detected
      immunohistochemically, and the severity of arthroscopic features (synovitis,
      degenerative changes of articular eminence, and adhesion) in 30 patients with ID
      of the TMJ were assessed and the correlations between them were analyzed
      statistically. RESULTS: RANKL expression was detected in the cytoplasm of
      synovial lining cells, endothelial cells, and fibroblast cells. However, there
      were no correlations between RANKL expression in any cell type and the severity
      of arthroscopic features. CONCLUSION: These observations indicated that the
      cellular source of osteoclastic differentiation exists in TMJ with ID and may
      provide insight into the mechanism of osteoclast differentiation.

PMID- 17560138
TI  - Factors associated with underdiagnosis from incisional biopsy of oral leukoplakic
      lesions.
AB  - OBJECTIVES: Incisional biopsy is accepted by most clinicians as a dependable way
      of assessing the nature of oral leukoplakia (OL). The aim of the present study
      was to investigate its reliability and analyze risk factors associated with
      underdiagnosis from incisional biopsy. STUDY DESIGN: A cross-sectional
      retrospective study was conducted in 242 patients with a clinical diagnosis of
      OL. The discrepancy between provisional diagnosis (from incisional biopsy) and
      definitive diagnosis (from resection specimen) was analyzed and correlated with
      clinical variables. Patients who had incisional biopsy taken from a single
      location and those who received multiple-site biopsies were analyzed separately.
      RESULTS: In the 200 cases receiving single-site biopsy, the agreement rate
      between provisional and definitive diagnoses was only 56%, and underdiagnosis
      from incisional biopsy was noted in 29.5% of patients. Underdiagnosis rate in the
      42 patients receiving multiple-site biopsies was significantly lower (11.9%; P <
      .05). The rate of unexpected carcinoma in resection specimen was also
      significantly lower in the multiple-biopsy patients than in the single-biopsy
      patients (2.4% vs. 12.0%; P < .05). For the single-biopsy group, multivariate
      analysis revealed that clinical appearance significantly influenced the risk of
      underdiagnosis and unexpected carcinoma (both P < .05). Compared with homogeneous
      lesions, nonhomogeneous OL were more prone to be underdiagnosed (adjusted odds
      ratio [AOR] 2.36, 95% confidence interval [CI] 1.16-4.82) and have carcinoma
      undetected by incisional specimen (AOR 15.94, 95% CI 2.09-121.72). CONCLUSIONS:
      Incisional biopsy was found to have limitations in the assessment of OL,
      especially for nonhomogeneous lesions. Clinicians should be conscious of the
      possible underdiagnosis from incisional biopsy, and multiple biopsies should be
      taken whenever they think that it is necessary.

PMID- 17560139
TI  - Genetic damage in human peripheral lymphocytes exposed to antimicrobial
      endodontic agents.
AB  - OBJECTIVE: Formocresol, paramonochlorophenol, or calcium hydroxide have been
      widely used in dental practice to eradicate bacteria and consequently to produce
      root canal disinfection. Taking into consideration strong evidence for a
      relationship between DNA damage and carcinogenesis, the purpose of the present
      study was to evaluate the genotoxic effects of antimicrobial endodontic compounds
      in human peripheral lymphocytes by single-cell gel (comet) assay. This technique
      detects DNA strand breaks in individual cells. STUDY DESIGN: A total of 10 microL
      of the tested substance solution (formocreso1, paramonochlorofeno1, and calcium
      hydroxide at 100-microg/mL concentration) was added to human peripheral
      lymphocytes from 10 volunteers for 1 hour at 37 degrees C. The negative control
      group was treated with vehicle control (PBS) for 1 hour at 37 degrees C, as well.
      For the positive control group, lymphocytes were exposed to hydrogen peroxide at
      100 microM during 5 minutes on ice. RESULTS: No DNA breakage was detected after a
      treatment of peripheral lymphocytes by formocresol, paramonochlorophenol, or
      calcium hydroxide at 100 microg/mL. CONCLUSIONS: In summary, our results indicate
      that exposure to formocresol, paramonochlorophenol, or calcium hydroxide may not
      be a factor that increases the level of DNA lesions in human peripheral
      lymphocytes as detected by single-cell gel (comet) assay.

PMID- 17560140
TI  - Computerized tomographic findings in bisphosphonate-associated osteonecrosis of
      the jaw in patients with cancer.
AB  - OBJECTIVES: To study bisphosphonate-associated osteonecrosis of the jaw with
      respect to radiographic, demographic, and clinical features. STUDY DESIGN: Thirty
      two patients with painful exposed bone in the jaws subsequent to treatment with
      bisphosphonates for various neoplastic diseases were examined with both dental
      panoramic radiograph and multislice spiral computerized tomography (CT). Each
      case was assessed for the following radiologic signs: structural alteration of
      trabecular bone, cortical bone erosion, osteosclerosis, small sequestrum,
      extensive sequestrum, and presence of periosteal new bone. The McNemar, chi2, and
      Kruskall-Wallis tests were performed to analyze the association between
      radiologic signs, demographic data, clinical aspects of the lesion, and type and
      duration of bisphosphonate therapy. Hierarchical cluster analysis was used to
      group patients into categories on the basis of CT signs and dental panoramic
      radiograph signs. The agreement between CT and dental panoramic radiograph
      clusters was analyzed by kappa index. RESULTS: Dental panoramic radiograph proved
      positive for features of osteonecrosis in 18 cases and CT in 30. Computerized
      tomography was far superior to dental panoramic radiograph in detecting all the
      radiologic signs. The cluster analysis applied to CT signs showed a
      classification of the 32 patients in 4 categories characterized by an increasing
      number of signs coherent with the clinical extension of the lesions. Structural
      alteration of trabecular bone and cortical bone erosion, a constant finding in
      the 30 positive CTs, could be sometimes differentiated only with difficulty from
      those due to recent extraction. Dental panoramic radiograph missed the correct
      diagnosis of sequestration in 15 cases. Intense periosteal reaction was often
      found. The most extensive maxillary lesions were associated with new bone
      formation in Schneider mucous membrane, never described previously, and oroantral
      communications. CONCLUSIONS: Dental panoramic radiograph were found to be of
      limited use in assessing bisphosphonate-associated osteonecrosis of the jaw in
      patients for whom CT imaging was subsequently ordered.

PMID- 17560141
TI  - The therapeutic use of botulinum toxin in cervical and maxillofacial conditions:
      an evidence-based review.
AB  - INTRODUCTION: The role of botulinum toxin as a therapeutic agent for several
      conditions is expanding. We sought to determine if botulinum toxin is safe and
      effective in treating patients with cervical dystonia and maxillofacial
      conditions. Our purpose was to establish a safety and efficacy profile to
      determine whether or not this treatment may be used prophylactically in patients
      undergoing dental implant therapy. METHODS: We performed a systematic search of
      the literature to identify randomized clinical trials evaluating patients treated
      with botulinum toxin as an adjunct to dental implant therapy, maxillofacial
      conditions including temporomandibular disorders (TMD), and cervical dystonia.
      RESULTS: Four randomized controlled trials (RCTs) met our search criteria in the
      area of cervical dystonia and chronic facial pain. No RCTs were identified
      evaluating dental implant therapy. Patients with cervical dystonia exhibited
      significant improvements in baseline functional, pain, and global assessments
      compared to placebo. Adverse events were mild and transient with numbers needed
      to harm (NNH) ranging from 12 to 17. Patients with chronic facial pain improved
      significantly from baseline in terms of pain compared to placebo. Rates of
      adverse events were less than 1%. CONCLUSION: Botulinum toxin appears relatively
      safe and effective in treating cervical dystonia and chronic facial pain
      associated with masticatory hyperactivity. No literature exists evaluating its
      use in dental implantology. Randomized clinical trials are warranted to determine
      its safety and efficacy in dental implantology and other maxillofacial conditions
      such as bruxism.

PMID- 17560142
TI  - Tongue lesions and isolated hypoglossal nerve palsy: a case report.
AB  - We report the case of a patient with oral lesions on the upper surface of his
      tongue. Intraoral examination revealed marked right-sided hemiatrophy of the
      tongue with fasciculation, partial deviation of the tongue on the right side, and
      inability of the patient to completely deviate the tongue toward the left side of
      his mouth on protrusion. A magnetic resonance image showed presence of a tumor
      lesion characterized by irregular margins localized in the intradural space, with
      a lateral extension along the omolateral hypoglossal canal. This was consistent
      with the diagnosis of a hypoglossal neurinoma, later confirmed by the
      histopathologic examination.

PMID- 17560143
TI  - Correction by desmopressin of bleeding following dental extraction in a patient
      under antithrombotic therapy.

PMID- 17560144
TI  - Chronic ulcerative stomatitis: diagnostic and management challenges--four new
      cases and review of literature.
AB  - Chronic ulcerative stomatitis (CUS) is a recently described mucocutaneous disease
      characterized by involvement of mucosal surfaces and skin. The disease usually
      presents in the form of painful oral ulcers and has been seen predominantly among
      older women. Clinically, CUS patients may exhibit erosive or ulcerative lesions
      of oral mucosa resembling erosive lichen planus and/or other vesiculobullous
      lesions. Routine histology may exhibit features of lichenoid mucositis and is
      often nondiagnostic. Direct immunofluorescence studies of mucosal or skin
      biopsies usually reveal a unique pattern of IgG bound to nuclei of keratinocytes
      of the basal and parabasal cell layers. Chronic ulcerative stomatitis exhibits a
      unique resistance to standard treatments available, including topical and
      systemic corticosteroids and immunomodulatory medications. However, long-lasting
      favorable clinical responses may be achieved with hydroxychloroquine
      pharmacotherapy. We present the clinicoimmunopathologic findings of four cases of
      CUS and discuss the varied clinical, microscopic spectrum, and treatment for this
      chronic, debilitating, and often recalcitrant condition. A systematic review of
      the literature, including 35 previously reported cases, is presented.

PMID- 17560145
TI  - Linear IgA dermatosis with exclusive mucosal involvement or mucous membrane
      pemphigoid?

PMID- 17560146
TI  - An unusually large asymptomatic periapical lesion that presented as a random
      finding on a panoramic radiograph.
AB  - OBJECTIVE: This report presents an asymptomatic case of a large mandibular
      periapical lesion that was discovered as a random finding on a panoramic
      radiograph. SUMMARY: A panoramic radiograph was asked for removal of wisdom
      tooth's roots. The radiograph revealed an unusually large lesion extending from
      lower premolar to opposite lower canine. Upon clinical examination a discolored
      lower central incisor and an elevation of the vestibule were visible. The
      discolored tooth did not respond to thermal and electrical vitality tests and was
      not tender to percussion. No history of trauma was recorded and all other teeth
      in the lower anterior area were vital. Surgical excision of the lesion was
      decided after denial of conservative treatment by the patient. The result was
      satisfactory and 6 months after the operation new bone was formed at the site of
      the lesion. CONCLUSIONS: Dentists should be very careful on clinical examination
      and should not omit any details. Before beginning any treatment a careful and
      complete clinical and radiographic examination is needed to supply all the
      required information. Small clinical signs such as a discolored tooth should
      alert the dentist.

PMID- 17560147
TI  - The non-trivial functions of sleep.

PMID- 17560148
TI  - NADPH oxidases in fungi: diverse roles of reactive oxygen species in fungal
      cellular differentiation.
AB  - Synthesis of reactive oxygen species (ROS) by specific NADPH oxidases (Nox) can
      serve both defense and differentiation signaling roles in animals and plants.
      Fungi have three subfamilies of NADPH oxidase. NoxA and NoxB have a structure
      very similar to the human gp91(phox). NoxC has in addition a Ca(2+) binding motif
      as found in the human Nox5 and plant Rboh families of NADPH oxidases. A survey of
      fungal genomes identified up to four Nox genes in some fungal species, but Nox
      genes are absent from available genomes of the hemiascomycete yeasts, unicellular
      Basidiomycetes and Zygomycetes, reflecting the diversity of fungal life forms.
      Specific isoforms of Nox have been shown by genetic analysis to be required for
      various physiological processes and cellular differentiations, including
      development of sexual fruiting bodies, ascospore germination, hyphal defense,
      hyphal growth in both mutualistic and antagonistic plant-fungal interactions.
      This review provides an overview of our current knowledge of fungal NADPH
      oxidases, including Nox distribution in the fungal kingdom, Nox structure and
      regulation, and known biological functions of this important group of enzymes.

PMID- 17560149
TI  - Bite wounds involving the spine: characteristics, therapy and outcome in seven
      cases.
AB  - Medical records of five dogs and two cats with bite wounds to the spine were
      reviewed. All dogs were bitten in the cervical spine and presented as
      quadriparetic. Both cats were bitten at the lumbar spine; one was paraparetic and
      the other paraplegic. Concomitant injuries to structures other than the spine
      were seen in two cases. Radiographic findings included vertebral fractures in all
      cases. Medical therapy included antibiotics (7/7), methylprednisolone sodium
      succinate (4/7) and analgesia (7/7). Five cases underwent minor (4/5) or
      extensive (1/5) surgical debridement. All cervical fractures were stabilized with
      fiberglass casts and animals with lumbar injury were cage rested for a month. Six
      of the cases survived, five of which regained good to excellent ambulatory
      ability within the first month. Although, the numbers of reported cases are
      limited, this study shows that adequate surgical debridement and wound drainage
      combined with external coaptation can be sufficient to manage bite wounds that
      involve the spine.

PMID- 17560150
TI  - Is there a benefit from an early booster vaccination in the control of equine
      influenza?
AB  - Conventional equine influenza vaccination schedules consist of a primary course
      of two vaccinations given 4-6 weeks apart followed by a third vaccination
      (booster) given approximately 5 months later. In between the primary course and
      the third vaccination, horses are generally considered not to be adequately
      protected against influenza. This study aimed to investigate whether Thoroughbred
      foals would benefit from a vaccination schedule in which the third vaccination
      was given earlier than in conventional vaccination schedules. The vaccines used
      were an inactivated whole virus equine influenza vaccine and an inactivated whole
      virus combination vaccine containing equine influenza and equine herpesvirus
      antigens. Four groups of foals were vaccinated with the two vaccines according to
      a conventional and an accelerated vaccination schedule in which the third
      vaccination was given 14 weeks after the first administration. In both groups,
      the fourth vaccination was given at the normally recommended interval of 26 weeks
      after the third vaccination for the combination vaccine and 52 weeks after the
      third vaccination with the influenza only vaccine. The horses were 4-11 months of
      age and seronegative for influenza. Immunological responses after vaccination
      were monitored for several months using the single radial haemolysis test. The
      results indicated that 28 weeks after the first vaccination, antibody levels in
      horses vaccinated according to the accelerated schedule were not significantly
      higher than in horses vaccinated according to the conventional schedule. In
      addition, the total level of antibody production (area under the curve) was not
      significantly different at that point although antibody titres were slightly
      higher (but not significantly so) between 16-30 weeks in the accelerated
      schedule. Between the third and fourth doses, horses vaccinated according to the
      accelerated schedule had antibodies against influenza below the level required
      for clinical protection for 39 and 18 weeks for the influenza only and the
      combination vaccine, respectively, whereas those vaccinated according to the
      conventional schedule had antibody titres below the level for clinical protection
      for 9-15 weeks in the corresponding period for both vaccines. Horses vaccinated
      according to the accelerated schedule with the combination vaccine had lower
      antibody titres after the fourth vaccination than those vaccinated according to
      the conventional schedule after the third vaccination, although antibody titres
      prior to vaccination were similar. For the influenza only vaccine, titres after
      the accelerated fourth administration were not different to those after the
      conventional third vaccination. There was no benefit from early booster
      vaccinations with the vaccines used in this study, so for these vaccines the
      conventional schedule provided better protection than the selected accelerated
      alternative. This may contrast with some other vaccine formulations, although a
      direct comparison using similar protocols has not been made.

PMID- 17560151
TI  - A low-cost implementation of EPR detection in a dissolution DNP setup.
AB  - The implementation of electron paramagnetic resonance (EPR) detection in a low
      temperature dissolution dynamic nuclear polarization (DNP) setup is presented.
      Using a coil oriented parallel to the static magnetic field, the change of the
      longitudinal magnetization of free radicals is measured upon resonant irradiation
      of an amplitude or frequency modulated microwave (mw) field. The absorption EPR
      spectrum is measured if the amplitude of the mw field is modulated, whilst the
      first derivative of the spectrum is obtained with frequency modulation. Using a
      burst of pulses, it is also possible to perform pump-probe experiments such as
      saturation-recovery or electron-electron double resonance experiments.
      Furthermore, the magnetization could be monitored in a time-resolved manner
      during amplitude modulation, thus making it possible to record its transient as
      it is approaching an equilibrium value. Experimental examples are shown with
      frozen solutions of trityl radical and TEMPO, two commonly used radicals for
      dissolution DNP experiments.

PMID- 17560152
TI  - Molecular docking and analysis of interactions between vascular endothelial
      growth factor (VEGF) and SPARC protein.
AB  - The extracellular module of SPARC/osteonectin binds to vascular endothelial
      growth factor (VEGF) and inhibits VEGF-stimulated proliferation of endothelial
      cells. In an attempt to identify the binding site for SPARC on VEGF, we
      hypothesized that this binding site could overlap at least partially the binding
      site of VEGF receptor 1 (VEGFR-1), as SPARC acts by preventing VEGF-induced
      phosphorylation of VEGFR-1. To this end, a docking simulation was carried out
      using a predictive docking tool to obtain modeled structures of the VEGF-SPARC
      complex. The predicted structure of VEGF-SPARC complex indicates that the
      extracellular domain of SPARC interacts with the VEGFR-1 binding site of VEGF,
      and is consistent with known biochemical data. Following molecular dynamics
      refinement, side-chain interactions at the protein interface were identified that
      were predicted to contribute substantially to the free energy of binding. These
      provide a detailed prediction of key amino acid side-chain interactions at the
      protein-protein interface. To validate the model further, the identified
      interactions will be used for designing mutagenesis studies to investigate their
      effect on binding activity. This model of the VEGF-SPARC complex should provide a
      basis for future studies aimed at identifying inhibitors of VEGF-induced
      angiogenesis.

PMID- 17560153
TI  - Growth hormone replacement throughout life: insights into age-related responses
      to treatment.
AB  - The adult growth hormone deficiency (GHD) syndrome is a well-defined clinical
      entity. Although the symptoms of GHD are not age specific, their relative
      importance differs depending on the patient's age, and the impact of GHD varies
      throughout adult life. Ceasing growth hormone (GH) therapy soon after final
      height in patients with severe GHD potentially limits somatic development by
      reducing accrual of bone and muscle mass. It is now recognized that the
      continuation of GH therapy in the transition years is required to achieve adult
      levels of somatic development. In middle age, the most worrying feature of GHD is
      the increase in cardiovascular risk, an important component of which is GHD
      related dyslipidemia. One of the most profound effects of GH therapy in this age
      group is the durable reduction in cholesterol levels. Elderly GH-deficient
      patients experience the symptoms of GHD over and above the signs of normal aging.
      Perhaps most importantly, these patients have impaired quality of life, with
      fatigue as a major component. Evidence is growing for improved quality of life
      with GH therapy in the elderly. This review describes the diagnosis, symptoms and
      treatment of GHD specific to the different age groups.

PMID- 17560154
TI  - Severe deficiencies of IGF-I, IGF-II, IGFBP-3, ALS and paradoxically high-normal
      bone mass in a child with insulin-resistance syndrome (Rabson-Mendenhall type).
AB  - Rabson-Mendenhall syndrome is a rare genetic disorder characterized by severe
      insulin resistance and hyperinsulinemia due to defects in signaling through the
      insulin receptor. Herein, we describe a new case of Rabson-Mendenhall syndrome in
      which investigations of the growth hormone (GH) - insulin-like growth factor
      (IGF) axis - reveal severe deficiencies in total and free insulin-like growth
      factor-I (IGF-I), IGF-II, IGF-binding protein-3 (IGFBP-3), and the acid labile
      subunit (ALS). Based on these findings, we anticipated significant bone deficits,
      as have been described in other clinical scenarios in which the IGF axis is
      significantly perturbed. Long-bone studies revealed no gross malformations.
      Paradoxically, DXA scanning revealed a total body bone density Z-score of +2.0
      (0.8 gm/cm(2)), suggesting an overall high-normal BMD for age and a high BMD
      corrected for bone or height age. The mechanisms by which BMD is protected from
      severe deficiencies in the IGF-axis are unknown, yet may involve enhanced IGF
      sensitivity, increased local production of IGFs, and/or supra-physiological
      concentrations of insulin substituting for the actions of IGFs in bone.

PMID- 17560155
TI  - Acute and chronic effects of growth hormone on renal regulation of electrolyte
      and water homeostasis.
AB  - For decades, growth hormone (GH) has been known to influence electrolyte and
      water handling in humans and animals. However, the molecular mechanisms
      underlying the GH-induced anti-natriuretic and anti-diuretic effects have
      remained elusive. This review will examine the existing literature on renal
      electrolyte and water handling following acute and chronic GH-exposure. Renal
      responses to GH differ in acute and chronic models. Acute application of GH
      results in a reduced urinary electrolyte and water excretion, whereas the chronic
      effects of GH are more diverse, as this state likely represents a complex mixture
      of primary and secondary actions of GH as well as compensatory mechanisms. During
      chronic GH-exposure an initial sodium retaining state often occurs, followed by a
      normalization of the urinary sodium excretion, although extracellular volume
      expansion still persists. We recently described a possible mechanism by which GH
      acutely increases renal electrolyte and water reabsorption, by modulation of the
      kidney specific Na(+), K(+), 2Cl(-) co-transporter (NKCC2). The primary aim of
      this review is to investigate how GH-induced regulation of NKCC2 may be involved
      in the complex renal changes previously described during acute and chronic GH. We
      propose, that the GH-induced increase in NKCC2 activity may explain the initial
      water and sodium retention seen in a number of studies. Moreover, renal changes
      seen during prolonged GH-exposure may now be seen on the background of the acute
      stimulation of NKCC2. Additionally, GH also promotes renal acidification, thus
      influencing renal acid/base handling. The GH-induced renal acidification is
      partly compatible with changes in NKCC2 activity. Finally, we review the
      available data on changes in hormonal systems affecting tubular transport during
      acute and chronic GH-exposure.

PMID- 17560156
TI  - Asymmetric dimethylarginine (ADMA) in vascular, renal and hepatic disease and the
      regulatory role of L-arginine on its metabolism.
AB  - Asymmetric dimethylarginine (ADMA), an inhibitor of nitric oxide synthase (NOS),
      has been identified as a new and emerging contributor to, or marker for,
      cardiovascular risk. The ADMA-mediated regulation of nitric oxide (NO) production
      is determined by the quantitative bioavailability of intracellular and
      extracellular ADMA. Dimethylarginine dimethylaminohydrolase (DDAH), which is
      ubiquitously expressed in tissues, especially liver and kidney, converts the
      majority of the ADMA to citrulline. In this review, we discuss a new regulatory
      mechanism for the metabolism of ADMA in which L-arginine acts as a competitive
      inhibitor of DDAH activity. This novel regulatory pathway is consistent with ADMA
      contributing to cardiovascular risk when levels are increased but not when levels
      are within the normal range. The pathway then has a physiological role in the
      regulation of NO production by preventing overproduction of NO. The regulatory
      role of L-arginine on ADMA may explain the unexpected outcomes in some L-arginine
      supplementation studies. This paper also reviews associations between the
      metabolism of ADMA and insulin resistance, smoking and homocysteine which are all
      associated with an increased risk of vascular disease.

PMID- 17560157
TI  - Coordinated control of both insulin secretion and insulin action through calpain
      10-mediated regulation of exocytosis?
AB  - Calpain-10 was first identified through a genome scan seeking to identify
      diabetes predisposition genes. Both genetic and functional data has since
      indicated that calpain-10 has an important role in insulin resistance and
      intermediate phenotypes, including those associated with adipocytes and skeletal
      muscle. Evidence presented in this issue by Brown, Yeaman, and Walker utilizes
      siRNA technology to specifically knock down calpain-10 expression, and suggests
      that calpain-10 facilitates GLUT4 translocation through effects on the distal
      secretory pathway. Calpain-10 is also an important molecule in the pancreatic
      beta-cell, where it has been shown to regulate exocytosis through partial
      proteolysis of a member of the secretory granule fusion machinery. In addition,
      calpain-10 has also been implicated in reorganization of the actin cytoskeleton
      that accompanies both GLUT4 vesicle translocation and insulin secretion. Taken
      together, these findings provide fresh hope for the development of novel diabetic
      treatments, utilizing either pharmacological activators that specifically target
      calpain-10, or through targeted calpain-10 gene therapy. Therapeutic intervention
      in this way could simultaneously enhance both insulin secretion and insulin
      action.

PMID- 17560158
TI  - Manifestation of hawkinsinuria in a patient compound heterozygous for
      hawkinsinuria and tyrosinemia III.
AB  - Mutations in the gene for 4-hydroxyphenylpyruvic acid dioxygenase (HPD) cause
      either autosomal recessive tyrosinemia type III or autosomal dominant
      hawkinsinuria. We report a 6-month-old Indian infant who is compound heterozygous
      for both alleles and who has hawkinsinuria but not tyrosinemia type III based on
      biochemical investigations. The HPD gene was directly sequenced in the proband
      and both parents. The mechanistic model of the enzymatic function was built using
      the known structure of rat HPD. We identified a novel hawkinsinuria mutation,
      Asn241Ser, and a known tyrosinemia type III mutation, Ile335Met, in trans
      configuration. The structural analysis of the active site revealed that the
      IIe335Met mutation is situated in the close vicinity of one of the two highly
      conserved Phe rings which stack with the phenol ring of the substrate. The
      Asn241Ser mutation is situated further away from the 4-hydroxyphenylpyruvate
      binding pocket. Assuming that Asn241Ser causes hawkinsinuria, we propose
      positioning the dioxygen molecule in the HPD-catalyzed reaction as a novel role
      for the Asn residue. The IIe335Met allele is equivalent to a null mutation while
      the Asn241Ser allele results in a partially active enzyme with an uncoupled
      turnover causing hawkinsinuria.

PMID- 17560159
TI  - Pregnancy-related hip diseases: incidence and diagnoses.
AB  - BACKGROUND: Pregnancy-related hip diseases epidemiology has been poorly
      evaluated. We report our experience of gestational and postpartum hip diseases
      and evaluate their incidence. METHODS: (1) Prospective survey: all pregnant or
      early postpartum women suspected to have hip involvement during their follow-up
      in an Obstetric unit were referred to a rheumatologist. If clinically confirmed,
      magnetic resonance imaging (MRI) and additional investigations as needed were
      performed. This survey had 2 years duration. (2) Retrospective study: all cases
      of definite (with MRI confirmation) pregnancy-related hip disease referred to our
      Rheumatology unit during the past 15 years were analyzed. RESULTS: During the 2
      year prospective survey, 3 patients (4 hips) of pregnancy-related hip disease
      were observed over 4900 pregnancies (1 case of transient osteoporosis of the hip
      (TOH) and 2 cases of occult fracture of the femoral head). During the 15-year
      retrospective study, 12 patients (17 hips) with hip diseases during pregnancy or
      early postpartum were identified. There were 6 patients (9 hips) with TOH, 4
      patients (6 hips) with occult fracture of the femoral head, 1 patient with
      osteonecrosis of the femoral head, and 1 coxitis in a patient with ankylosing
      spondylitis. Differentiating diagnosis between TOH and occult fractures could
      only be made by MRI. Five of the 6 women with TOH had osteopenia at the lumbar
      spine at dual energy X-ray absorptiometry (DEXA). The 4 women with occult
      fractures had either osteopenia or osteoporosis at the lumbar spine. CONCLUSION:
      Hip diseases are infrequent during pregnancy and early postpartum. Transient
      osteoporosis of the hip and occult stress fractures of the femoral head appear
      the main causes and those diagnoses justify evaluation for an underlying bone
      fragility. Osteonecrosis is very rare in this setting.

PMID- 17560160
TI  - Leptin stimulates endogenous cholesterol synthesis in human monocytes: New role
      of an old player in atherosclerotic plaque formation. Leptin-induced increase in
      cholesterol synthesis.
AB  - The role of leptin in the pathomechanism of atherosclerosis, through its free
      radical generating ability is established. Its effect however, on the regulation
      of intracellular cholesterol synthesis has not been studied. The aim of the
      present study was to elucidate whether leptin influences endogenous cholesterol
      synthesis in monocytes. Furthermore, leptin signaling to HMG CoA reductase in
      control and hypercholesterolemic monocytes were compared. The in vitro effect of
      leptin was studied on freshly isolated human monocytes obtained from healthy
      control volunteers and patients with hypercholesterolemia. Our results can be
      summarized as follows: (1) Leptin is able to increase endogenous cholesterol
      synthesis in human monocytes in vitro. (2) The cholesterol synthesis increasing
      effect of the hormone is more pronounced in hypercholesterolemic monocytes with
      high basal cholesterol biosynthesis. (3) The leptin-induced Ca(2+) signal was
      involved in the enhancement of HMG CoA reductase activation in monocytes from
      both controls and hypercholesterolemic patients. (4) In control monocytes the
      Ca(2+) signal originated from intracellular pools, whereas in patients, Ca(2+)
      influx and protein kinase C activation were found to be responsible for the
      leptin-effect. Mevalonate cycle inhibiting fluvastatin and 25-hydroxycholesterol
      decreased cholesterol production in leptin-stimulated monocytes. Our present
      study provides the first proof of the cholesterol synthesis enhancing effect of
      leptin through a statin-sensitive pathway in circulating monocytes. Furthermore
      our results suggest that leptin can be involved in the pathomechanism of
      atherosclerotic plaque formation also through its effect on cholesterol
      biosynthesis in monocytes.

PMID- 17560161
TI  - Developmental change and the nature of learning in childhood.
AB  - How do children acquire humankind's remarkable cognitive skills? Why are the
      abilities children acquire readily, such as native-language fluency, harder for
      adults? Although attitudes to these questions span the continuum from nativism to
      learning theory, answers remain elusive. We relate a recent model of language
      acquisition in childhood to advances in the neuroscience of adult cognitive
      control, to propose a domain-general shift in the architecture of learning in
      childhood. The timing of this supports children's imitative, unsupervised
      learning of social and linguistic conventions before the maturation of cognitive
      control gives individuals greater self-direction, which causes learning to become
      less conventionalized and more idiosyncratic. These changes might represent an
      important adaptation supporting the development and learning of cultural and
      linguistic conventions.

PMID- 17560162
TI  - Maturation and degradation of RNA in bacteria.
AB  - RNA decay plays an important role, not only in recycling nucleotides but also in
      determining the rapidity with which cells can react to changing growth
      conditions. The degradation process can be regulated, thus providing an often
      underestimated means of controlling gene expression. Recent developments in the
      field of RNA maturation and decay in two key model organisms, Escherichia coli
      and Bacillus subtilis, include the resolution of the structures of many of the
      participants in these processes in E. coli and the identification of an enzyme in
      B. subtilis that appears to fit the bill as a major player in RNA decay in this
      organism.

PMID- 17560163
TI  - Analysis of genetic variants of the poly(ADP-ribose) polymerase-1 gene in breast
      cancer in French patients.
AB  - Poly(ADP-ribose) polymerase-1 (PARP-1) is a nuclear enzyme that catalyzes the
      poly(ADP-ribosyl)ation of target proteins in response to DNA damage and has been
      proposed to play a role in DNA repair, recombination, transcription, cell death,
      cell proliferation, as well as in stabilization of the genome. We have recently
      shown that PARP-1 deficiency causes mammary tumorigenesis in mice. In the present
      study, we investigated whether genetic variants and single nucleotide
      polymorphisms (SNPs) of PARP-1 contribute to human breast cancer. To this end, we
      screened all PARP-1 exons, 7.1kb of intron-exon junction and 1.0-kb promoter
      sequences in 83 French patients with breast cancer and 100 controls by direct
      sequencing of genomic DNA. Twenty rare genetic variants of PARP-1, including
      c.1148C>A (Ser383Tyr), c.1354C>A (Arg452Arg), c.2819A>G (Lys940Arg) were detected
      in nine (10.8%) breast cancers of these patients. Among 31 polymorphic sites
      examined, five haplotype-tagging SNPs (htSNPs) of PARP-1 were identified.
      Interestingly, the genotype distribution of htSNP c.852T>C (Ala284Ala) was likely
      associated with loss of estrogen- and progesterone-receptor expression. The
      present study implies that genetic variants of PARP-1 may contribute to breast
      cancerogenesis and that PARP-1 htSNP c.852T>C (Ala284Ala) may influence hormonal
      therapy of breast cancer.

PMID- 17560164
TI  - Exploring a model-driven architecture (MDA) approach to health care information
      systems development.
AB  - OBJECTIVE: To explore the potential of the model-driven architecture (MDA) in
      health care information systems development. METHODS: An MDA is conceptualized
      and developed for a health clinic system to track patient information. A
      prototype of the MDA is implemented using an advanced MDA tool. The UML provides
      the underlying modeling support in the form of the class diagram. The PIM to PSM
      transformation rules are applied to generate the prototype application from the
      model. RESULTS: The result of the research is a complete MDA methodology to
      developing health care information systems. Additional insights gained include
      development of transformation rules and documentation of the challenges in the
      application of MDA to health care. Design guidelines for future MDA applications
      are described. The model has the potential for generalizability. The overall
      approach supports limited interoperability and portability. CONCLUSION: The
      research demonstrates the applicability of the MDA approach to health care
      information systems development. When properly implemented, it has the potential
      to overcome the challenges of platform (vendor) dependency, lack of open
      standards, interoperability, portability, scalability, and the high cost of
      implementation.

PMID- 17560165
TI  - The nature and occurrence of registration errors in the emergency department.
AB  - Research into the nature and occurrence of medical errors has shown that these
      often result from a combination of factors that lead to the breakdown of
      workflow. Nowhere is this more critical than in the emergency department (ED),
      where the focus of clinical decisions is on the timely evaluation and
      stabilization of patients. This paper reports on the nature of errors and their
      implications for patient safety in an adult ED, using methods of ethnographic
      observation, interviews, and think-aloud protocols. Data were analyzed using
      modified "grounded theory," which refers to a theory developed inductively from a
      body of data. Analysis revealed four classes of errors, relating to errors of
      misidentification, ranging from multiple medical record numbers, wrong patient
      identification or address, and in one case, switching of one patient's
      identification information with those of another. Further analysis traced the
      root of the errors to ED registration. These results indicate that the nature of
      errors in the emergency department are complex, multi-layered and result from an
      intertwined web of activity, in which stress in the work environment, high
      patient volume and the tendency to adopt shortcuts play a significant role. The
      need for information technology (IT) solutions to these problems as well as the
      impact of alternative policies is discussed.

PMID- 17560166
TI  - Clinical impact of influenza immunization in patients with liver cirrhosis.
AB  - BACKGROUND: Influenza vaccine is considered to reduce influenza-related morbidity
      and mortality in patients with underlying chronic medical conditions. Yet in
      liver cirrhosis, influenza vaccines have received little attention in determining
      the potential benefits. OBJECTIVES: We intended to evaluate the clinical benefits
      of influenza vaccination and clinical outcomes of influenza in patients with
      liver cirrhosis. METHODS: We performed a controlled, prospective clinical trial
      of 311 cirrhotic patients, who were enrolled in October 2004. Among them, 198
      patients were vaccinated with a trivalent influenza vaccine and the rest were not
      vaccinated. Both groups were followed with respect to the occurrence of influenza
      like illness (ILI) until May 2005. RESULTS: Overall incidences of ILI (p=0.064)
      and culture positivity of influenza (p=0.009) were remarkably higher in
      unvaccinated group compared to the vaccinated group. Most of the cirrhotic
      patients with influenza had fever (91.6%) and complained of myalgia (83.3%)
      without respiratory symptoms, which were not typical clinical presentations of
      influenza. Influenza vaccination also decreased influenza-related complication
      rates in patients with liver cirrhosis. CONCLUSION: Influenza vaccination should
      be recommended to all cirrhotic patients. High suspicion is required for early
      diagnosis and antiviral treatment, allowing for the frequent hepatic
      decompensation among cirrhotic patients.

PMID- 17560167
TI  - Body mass index is an independent determinant of left atrial size.
AB  - BACKGROUND: Obesity is a risk factor for atrial fibrillation (AF) but the
      mechanisms underlying this association are unclear. We aimed to assess whether
      body mass index (BMI) is an independent determinant of left atrial size, in
      subjects in sinus rhythm. METHODS: Subjects were consecutive ambulatory patients
      aged >/=18 years who underwent outpatient transthoracic echocardiography at a
      major metropolitan teaching hospital in Sydney, Australia. At the time of
      examination, age, sex, height and weight were measured. Left atrial (LA) area was
      measured on ultrasound by planimetry. Left ventricular (LV) function and LV
      posterior wall thickness were measured by M-mode. RESULTS: Of 4859 consecutive
      subjects who underwent outpatient echocardiography at our institution over a
      three-year period, we analysed echocardiographic data from 2534 aged >/=18 years
      with confirmed sinus rhythm, normal LV contractility and no evidence of
      significant aortic or mitral valve disease. In these subjects (age 47+/-16.6
      years, BMI 27.1+/-6.1, 53% male), BMI was a significant predictor of LA size
      (p<0.001), independent of the significant influences of LV end-diastolic volume
      and LV posterior wall thickness. Average LA size was 18.5+/-4.0 cm(2) in those
      with normal BMI, 20.7+/-4.5 cm(2) in the overweight and 22.3+/-4.1cm(2) in obese
      subjects (p for trend <0.001). CONCLUSIONS: Obesity is associated with increased
      left atrial size in subjects undergoing clinically indicated echocardiography,
      independent of the effects of left ventricular size and posterior wall thickness.
      This may contribute, at least in part, to the rising incidence of atrial
      fibrillation in the community.

PMID- 17560168
TI  - The impact of oncology education on practice--a literature review.
AB  - Cancer care currently enjoys a high national profile in the UK, with a growing
      emphasis on cancer education for nurses and allied health professionals, however,
      there is dearth of research into the effectiveness and impact of cancer education
      on practice. This paper explores the context of cancer care and education and
      reviews the literature regarding the relationship between the two. It explores
      the assumption that education positively influences practice and contributes to
      the health care agenda by supporting the need for further research in this area.

PMID- 17560169
TI  - The SDF-1-CXCR4 signaling pathway: a molecular hub modulating neo-angiogenesis.
AB  - Pro-angiogenic bone marrow (BM) cells include subsets of hematopoietic cells that
      provide vascular support and endothelial progenitor cells (EPCs), which under
      certain permissive conditions could differentiate into functional vascular cells.
      Recent evidence demonstrates that the chemokine stromal-cell derived factor-1
      (SDF-1, also known as CXCL12) has a major role in the recruitment and retention
      of CXCR4(+) BM cells to the neo-angiogenic niches supporting revascularization of
      ischemic tissue and tumor growth. However, the precise mechanism by which
      activation of CXCR4 modulates neo-angiogenesis is not clear. SDF-1 not only
      promotes revascularization by engaging with CXCR4 expressed on the vascular cells
      but also supports mobilization of pro-angiogenic CXCR4(+)VEGFR1(+) hematopoietic
      cells, thereby accelerating revascularization of ischemic organs. Here, we
      attempt to define the multiple functions of the SDF-1-CXCR4 signaling pathway in
      the regulation of neo-vascularization during acute ischemia and tumor growth. In
      particular, we introduce the concept that, by modulating plasma SDF-1 levels, the
      CXCR4 antagonist AMD3100 acutely promotes, while chronic AMD3100 treatment
      inhibits, mobilization of pro-angiogenic cells. We will also discuss strategies
      to modulate the mobilization of essential subsets of BM cells that participate in
      neo-angiogenesis, setting up the stage for enhancing revascularization or
      targeting tumor vessels by exploiting CXCR4 agonists and antagonists,
      respectively.

PMID- 17560171
TI  - Risk factors for recurrent venous thromboembolism in the European collaborative
      paediatric database on cerebral venous thrombosis: a multicentre cohort study.
AB  - BACKGROUND: The relative importance of previous diagnosis and hereditary
      prothrombotic risk factors for cerebral venous thrombosis (CVT) in children in
      determining risk of a second cerebral or systemic venous thrombosis (VT),
      compared with other clinical, neuroimaging, and treatment variables, is unknown.
      METHODS: We followed up the survivors of 396 consecutively enrolled patients with
      CVT, aged newborn to 18 years (median 5.2 years) for a median of 36 months
      (maximum 85 months). In accordance with international treatment guidelines, 250
      children (65%) received acute anticoagulation with unfractionated heparin or low
      molecular weight heparin, followed by secondary anticoagulation prophylaxis with
      low-molecular weight heparin or warfarin in 165 (43%). RESULTS: Of 396 children
      enrolled, 12 died immediately and 22 (6%) had recurrent VT (13 cerebral; 3%) at a
      median of 6 months (range 0.1-85). Repeat venous imaging was available in 266
      children. Recurrent VT only occurred in children whose first CVT was diagnosed
      after age 2 years; the underlying medical condition had no effect. In Cox
      regression analyses, non-administration of anticoagulant before relapse (hazard
      ratio [HR] 11.2 95% CI 3.4-37.0; p<0.0001), persistent occlusion on repeat venous
      imaging (4.1, 1.1-14.8; p=0.032), and heterozygosity for the G20210A mutation in
      factor II (4.3, 1.1-16.2; p=0.034) were independently associated with recurrent
      VT. Among patients who had recurrent VT, 70% (15) occurred within the 6 months
      after onset. CONCLUSION: Age at CVT onset, non-administration of anticoagulation,
      persistent venous occlusion, and presence of G20210A mutation in factor II
      predict recurrent VT in children. Secondary prophylactic anticoagulation should
      be given on a patient-to-patient basis in children with newly identified CVT and
      at high risk of recurrent VT. Factors that affect recanalisation need further
      research.

PMID- 17560172
TI  - Autoimmune disease in families with multiple sclerosis: a population-based study.
AB  - BACKGROUND: Evidence of an association between multiple sclerosis (MS) and other
      autoimmune diseases would substantiate the hypothesis that MS is an autoimmune
      disease, and implicate a common mechanism. We aimed to investigate and compare
      the rate of autoimmune disease in MS patients, in their first-degree relatives,
      and in their unrelated spouses. METHODS: We used data from a national,
      multicentre, population-based sample to investigate the rate of autoimmune
      disease in 5031 MS patients, 30 259 of their first-degree relatives, and 2707
      spousal controls. We asked patients and controls whether they had any of ten
      autoimmune diseases: Crohn's disease, ulcerative colitis, rheumatoid arthritis,
      type 1 diabetes, psoriasis, pernicious anaemia, systemic lupus erythematosus,
      autoimmune thyroid disease, vitiligo, and myasthenia gravis. MS probands were
      also asked whether their first-degree relatives had Crohn's disease, ulcerative
      colitis, rheumatoid arthritis, or type 1 diabetes. FINDINGS: After correction for
      age and sex, we did not identify any increased risk of autoimmune diseases in MS
      patients compared with their spousal controls (odds ratio [OR]=1.07, 95% CI 0.86
      1.23, chi(2)=0.47, p=0.49), or in the first-degree relatives of MS probands
      compared with controls (OR=0.89, 0.63-1.17, chi(2)=1.11, p=0.29). However, the
      reported frequency of autoimmune diseases did differ according to the sex of the
      interviewee (female vs male patients chi(2)=92.2, p<0.0001; female vs male
      spousal controls chi(2)=87.1, p<0.0001). MS patients had slightly higher rates of
      thyroid disease and pernicious anaemia than did controls, which is consistent
      with MHC associations for these diseases, but this effect disappeared when
      results were adjusted for sex. For eight other diseases the rates were similar in
      MS patients and controls. Families with multiple cases of MS were no more likely
      to report autoimmune diseases than families with single MS cases. INTERPRETATION:
      When data were adjusted for sex, no excess of common autoimmune diseases could be
      identified in MS patients or their families, including multicase pedigrees. Our
      results suggest that women are more aware of family medical histories than men,
      which emphasises the potential for ascertainment bias in unstratified data for a
      sex-limited disease. Family histories should thus be taken from male patients in
      the presence of a spouse.

PMID- 17560173
TI  - A unique T cell subset described as CD4loCD40+ T cells (TCD40) in human type 1
      diabetes.
AB  - Human T1D pancreatic lymph nodes contain diabetes-autoantigen responsive T cells
      but identification of such T cells in the periphery has proven difficult. Here we
      describe a unique T cell subset defined by CD4(lo) and CD40 expression (T(CD40))
      that is significantly expanded in peripheral blood of T1D but not control or T2D
      subjects. The HLA-DR3 and DR4 alleles are considered high risk factors for T1D
      and T(CD40) expansion occurs in T1D subjects carrying HLA DR3 or DR4 haplotypes
      but, T1D subjects who do not carry either DR3 or DR4 haplotypes still have an
      expanded percentage of T(CD40) cells. Non-autoimmune subjects, even DR3(+) and
      DR4(+), do not have elevated percentages of T(CD40) cells. The majority of
      T(CD40) cells in T1D carry a memory phenotype and a portion of those proliferates
      when exposed to diabetes-associated self-antigens. A greater number of memory
      T(CD40) cells express CXCR3 when compared to CD40(-) memory cells and that number
      is significantly expanded in T1D compared to control subjects. If only total
      CD4(+) T cells are compared no difference in CXCR3 is seen. Furthermore, T(CD40)
      cells produce a Th1, pro-inflammatory cytokine profile. In healthy controls,
      T(CD40) cells have equally Th1 and Th2 profiles.

PMID- 17560174
TI  - Expression of Mycobacterium tuberculosis Ku and Ligase D in Escherichia coli
      results in RecA and RecB-independent DNA end-joining at regions of microhomology.
AB  - Unlike Escherichia coli, Mycobacterium tuberculosis (Mt) expresses a Ku-like
      protein and an ATP-dependent DNA ligase that can perform non-homologous end
      joining (NHEJ). We have expressed the Mt-Ku and Mt-Ligase D in E. coli using an
      arabinose-inducible promoter and expression vectors that integrate into specific
      sites in the E. coli chromosome. E. coli strains have been generated that express
      the Mt-Ku and Mt-Ligase D on a genetic background that is wild-type for repair,
      or deficient in either the RecA or RecB protein. Transformation of these strains
      with linearized plasmid DNA containing a 2bp overhang has demonstrated that
      expression of both the Mt-Ku and Mt-Ligase D is required for DNA end-joining and
      that loss of RecA does not prevent this double-strand break repair. Analysis of
      the re-joined plasmid has shown that repair is predominantly inaccurate and
      results in the deletion of sequences. Loss of RecB did not prevent the formation
      of large deletions, but did increase the amount of end-joining. Sequencing the
      junctions has revealed that the majority of the ligations occurred at regions of
      microhomology (1-4bps), eliminating one copy of the homologous sequence at the
      junction. The Mt-Ku and Mt-Ligase D can therefore function in E. coli to re
      circularize linear plasmid.

PMID- 17560175
TI  - Translocation of human ribosomal protein S3 to sites of DNA damage is dependant
      on ERK-mediated phosphorylation following genotoxic stress.
AB  - Besides its role in translation and ribosome maturation, human ribosomal protein
      S3 (hS3) is implicated in DNA damage recognition as reflected by its affinity for
      abasic sites and 7,8-dihydro-8-oxoguanine (8-oxoG) residues in DNA in vitro.
      Here, we demonstrate that hS3 is capable of carrying out both roles by its ex
      vivo translocation from the cytoplasm to the nucleus as a consequence of
      genotoxic stress. The translocation of hS3 is dependent on ERK1/2-mediated
      phosphorylation of a threonine residue (T42) of hS3. Two different ectopically
      expressed site-directed mutants of T42 failed to respond to conditions of
      genotoxic stress, thus providing a link between DNA damage and ERK1/2 dependent
      phosphorylation of hS3. Lastly, hS3 was traced in exposed cells to its co
      localization with 8-oxoG foci, raising the possibility that hS3 is a member of a
      cellular DNA damage response pathway that results in its interaction with sites
      of DNA damage.

PMID- 17560176
TI  - ENaCbeta and gamma genes as modifier genes in cystic fibrosis.
AB  - BACKGROUND: Clinical phenotype varies among cystic fibrosis (CF) patients with
      identical CF transmembrane conductance regulator (CFTR)genotype, suggesting that
      genetic modifiers exist. Transgenic mice that overexpress SCNN1beta present CF
      like lung disease symptoms. Mutations or variants in SCNN1beta may therefore
      potentially modulate the clinical phenotype in CF patients. METHODS: We analysed
      by DHPLC SCNN1beta and SCNN1gamma genes in 56 patients with classical CF.
      Patients were classified into two groups according to their CFTR genotype and
      their severity: 38 patients with severe genotype and an unexpectedly mild lung
      phenotype, and 18 patients with mild genotype and a severe lung phenotype.
      RESULTS: We found 3 patients out of 56 carrying at least one missense mutation.
      Two were novel (p.Thr313Met in SCNN1beta, p.Leu481Gln in SCNN1gamma) and two were
      previously described (p.Gly589Ser in SCNN1beta and p.Val546Ileu in SCNNgamma).
      p.Thr313Met has been identified in a CF patient with mild genotype and severe
      lung phenotype suggesting that it could act in increasing ENaC activity. The
      three other variants have been identified in CF patients with severe genotype and
      mild lung phenotype suggesting that they might decrease ENaC activity. However,
      the function of ENaC in the nasal epithelia of these patients, evaluated by nasal
      potential difference measurements, did not support the fact that these variants
      were functional, at least in nasal epithelium. CONCLUSION: Our results suggest
      that genetic variants in ENaCbeta and gamma genes do not modulate disease
      severity in the majority of CF patients.

PMID- 17560177
TI  - New physiological insights into exercise-induced diaphragmatic fatigue.
AB  - Data on the dynamic process and time-point of manifestation of exercise-induced
      diaphragmatic fatigue (DF) are lacking. Therefore, this study was aimed assessing
      dynamic changes of diaphragmatic strength during exercise and determining the
      time-point of DF manifestation. Fourteen trained subjects (maximal oxygen uptake
      (VO2(max)) 59.3+/-5.5 ml/min/kg) performed standardized exercise protocols
      (maximal workload: 85% VO2(max)) followed by recovery (6 min). Ergospirometric
      data and twitch transdiaphragmatic pressure (TwPdi) were consecutively assessed.
      DF was induced (TwPdi-rest: 2.34+/-0.26 versus TwPdi-end-recovery 2.01+/-0.21
      kPa, p<0.01). TwPdi progressively increased during exercise (TwPdi-rest: 2.34+/
      0.26 versus TwPdi-maximal-workload: 3.28+/-0.38 kPa, p<0.001). DF was detectable
      immediately after exercise-termination (TwPdi-maximal-workload: 3.28+/-0.38
      versus TwPdi-early-recovery 2.55+/-0.34 kPa, p<0.001). TwPdi during exercise was
      highly correlated to workload, VO2(max) and dyspnea (r=0.96/r=0.92/r=0.97; all
      p<0.0001). In conclusion, diaphragmatic strength progressively increases with
      increasing workload, and DF manifests after - rather than during - exercise. In
      addition, TwPdi is highly correlated to key-measures of ergospirometry, approving
      the physiological thesis that muscle strength is progressively enhanced and
      escapes fatiguing failure during high-intensity exercise performance.

PMID- 17560178
TI  - Liquid chromatography/negative ion electrospray tandem mass spectrometry method
      for the quantification of rosuvastatin in human plasma: application to a
      pharmacokinetic study.
AB  - A sensitive liquid chromatography/tandem mass spectrometric (LC-MS/MS) method was
      developed and validated for the determination of rosuvastatin in human plasma.
      The plasma samples were prepared using liquid-liquid extraction with ethyl ether.
      Chromatographic separation was accomplished on a Zorbax XDB-C18 (150 mm x 4.6 mm
      i.d., 5 microm) column. The mobile phase consisted of methanol-water (75:25, v/v,
      adjusted to pH 6 by aqueous ammonia). Detection of rosuvastatin and the internal
      standard (IS) hydrochlorothiazide was achieved by ESI MS/MS in the negative ion
      mode. The lower limit of quantification was 0.020 ng/ml by using 200 microl
      aliquots of plasma. The linear range of the method was from 0.020 to 60.0 ng/ml.
      The intra- and inter-day precisions were lower than 8.5% in terms of relative
      standard deviation (RSD), and the accuracy was within -0.3 to 1.9% in terms of
      relative error (RE). Compared with the existing methods, the validated method
      offered increased sensitivity. The method was successfully applied for the
      evaluation of pharmacokinetics of rosuvastatin after single oral doses of 5, 10
      and 20 mg rosuvastatin to 10 healthy volunteers.

PMID- 17560179
TI  - Determination of ochratoxin A in dry-cured meat products by a HPLC-FLD
      quantitative method.
AB  - A fast and sensitive method for the quantification of the mycotoxin ochratoxin A
      (OTA) in dry-cured meat products has been developed, which does not require a
      clean-up step, by HPLC with an alkaline mobile phase (pH 9.8). Validation
      procedures for specificity, trueness, ruggedness, stability, recovery and
      repeatability were performed. The decision limit (CC alpha) and the decision
      capability (CC beta) were calculated at 1.10 and 1.23 microg/kg, respectively.
      The procedure was applied to representative dehydration levels of dry-cured meat
      samples.

PMID- 17560180
TI  - Pharmacokinetics of HZ08 in rats by liquid chromatography-tandem mass
      spectrometry.
AB  - A selective and sensitive liquid chromatographic method coupled with ion spray
      tandem mass spectrometry detection (LC-MS/MS) was developed for the determination
      and pharmacokinetic study of N-cyano-1-[(3,4-dimethoxyphenyl)methyl]-3,4-dihydro
      6,7-dimethoxy-N'-octyl-2(1H)-isoquinoline-carboximidamide (HZ08, a candidate
      reversing agent for multidrug resistance of cancer) liposome injection in rat
      plasma. The analyte was extracted from plasma using liquid-liquid extraction by
      methyl tert-butyl ether with drotaverine as internal standard. The
      chromatographic separation was performed on a Kromasil-C18 column (150 mm x 4.6
      mm, i.d., 5 microm) with gradient elution. The tandem mass detection was made
      with electrospray ionization in positive ion selected reaction monitoring mode
      with argon collision-induced dissociation. The ion transitions were m/z 523.1 to
      342.1 for HZ08 at 27eV and m/z 398.1 to 326.1 at 35eV for the internal standard,
      respectively. The determination was validated to be accurate and precise for the
      analysis in the concentration range of 5-10,000 ng/ml for HZ08 with the lower
      limit of detection (LOD) being 1 ng/ml, when 0.1 ml of rat plasma sample was
      processed. The main pharmacokinetic parameters found for HZ08 after intravenous
      (i.v.) administration of its liposome injection at doses of 2, 4 and 8 mg/kg were
      as follows: C(max) (4511+/-681), (5553+/-1600) and (6444+/-950) ng/ml, T(max)
      (0.033+/-0), (0.056+/-0.048) and (0.033+/-0) h, t(1/2) (1.75+/-0.19), (1.63+/
      0.12) and (1.56+/-0.18) h, AUC(0-6) (899+/-112), (1238+/-190) and (1707+/-307) h
      ng/ml, AUC(0-infinity) (917+/-110), (1256+/-189) and (1723+/-306) h ng/ml, MRT
      (1.14+/-0.21), (1.01+/-0.13) and (1.16+/-0.17) h, CL (2.90+/-0.15), (3.01+/-0.74)
      and (4.11+/-0.59)l/h/kg, respectively. The plasma concentration-time profiles of
      HZ08 were best fitted with two-compartment models. Linear pharmacokinetics was
      found for HZ08 in rats after intravenous administration of the liposome
      injection.

PMID- 17560181
TI  - Helicity propensity and interaction of synthetic peptides from heptad-repeat
      domains of herpes simplex virus 1 glycoprotein H: a circular dichroism study.
AB  - The secondary structure of two synthetic peptides from heptad-repeat domains of
      herpes simplex virus 1 glycoprotein H was determined by circular dichroism. In
      particular, the propensity of these peptides to assume an ordered structure was
      investigated upon by changing the solvent's polarity and the temperature. A
      reduction of solvent polarity led to a significant increase in the alpha-helix
      content in the case of HR1, whereas only a slight change in the secondary
      structure was observed in the case of HR2. In both cases the conformational
      change followed a two-state transition model. The interaction of the peptides was
      monitored by the conformational change in the mixture with respect to the single
      peptides. However, formation of the complex did not significantly enhance thermal
      stability. A reliable estimation of the secondary structure was obtained by
      optimising the experimental conditions to collect CD data down to 180 nm, and by
      comparing the structure data yielded by different software packages.

PMID- 17560182
TI  - Protein-protein interactions and disease: use of S. cerevisiae as a model system.
AB  - Disease-causing mutations are increasingly being studied to see if they cause the
      loss or gain of protein-protein interactions. Because the interaction network of
      humans is poorly understood and difficult to investigate, here we propose the use
      of Saccharomyces cerevisiae as a model system for understanding the impact of
      disease-causing mutations on protein-protein interactions. Alignments of human
      disease-associated proteins and 379 yeast orthologs showed that 124 of these
      proteins have >40% sequence identity, with some orthologs having up to 89%
      identity. A total of 1826 amino acid mutations associated with human disease were
      found to map to invariant amino acids in yeast. These mutations were
      proportionately more likely to be non-conservative than non-disease associated
      polymorphisms for the same proteins (p=0.016). Importantly, 73 of the mutations
      mapped to protein-protein interaction domains, implying a direct link between
      mutation and changes in protein interactivity. In the manuscript, all alignment
      information and tables that map mutations and diseases to yeast orthologs are
      given. This will help researchers experimentally test the impact of mutations on
      protein-protein interactions in S. cerevisiae and, by homology, explore the role
      of such mutations in the genesis of human disease.

PMID- 17560183
TI  - Remineralization of human dentin using ultrafine bioactive glass particles.
AB  - Bioactive glass nanoparticles synthesized by flame spray synthesis were tested
      for their remineralization capabilities in vitro. After artificial
      demineralization with EDTA, human dentin was treated with 20-50nm size bioactive
      glass nanoparticles or a micrometer-sized, commercial reference material
      (PerioGlas) for up to 30 days. The degree of remineralization was measured using
      quantitative gravimetric methods (thermogravimetry, elemental analysis) and
      element-sensitive scanning electron microscopy imaging to detect new mineral
      precipitated on or within the demineralized tooth matrix. After treatment with
      bioactive glass nanoparticles for 10 or 30 days a pronounced increase in mineral
      content of the dentin samples suggested a rapid remineralization. The mechanical
      properties of the remineralized dentin samples were well below the stability of
      natural dentin. It is suggested that this lack of mechanical reconstitution may
      be attributed to an imperfect arrangement of the newly deposited mineral within
      the demineralized tooth matrix. Nevertheless, the substantially higher
      remineralization rate induced by nanometer-sized vs. micrometric bioactive glass
      particles corroborated the importance of particle size in clinical bioglass
      applications.

PMID- 17560184
TI  - Reply to 'Use of hydrogel pad in laser treatment of tattoos'.

PMID- 17560185
TI  - Heparin enhances osteoclastic bone resorption by inhibiting osteoprotegerin
      activity.
AB  - Heparin is a highly sulfated glycosaminoglycan and has been shown to activate
      osteoclastic bone resorption though how is not yet clear. Here we investigate the
      molecule involved in heparin-induced activation of osteoclasts using an in vitro
      osteoclast culture assay. The formation and activation of osteoclasts are induced
      by receptor activator of NFkappaB ligand (RANKL) on osteoblasts, and inhibited by
      osteoprotegerin (OPG), a decoy receptor of RANKL, which is secreted from
      osteoblasts. In a coculture of mouse bone marrow cells and osteoblasts treated
      with 1,25-dihydroxyvitamin D(3) and prostaglandin E(2) on dentin slices, the bone
      marrow cells differentiate into osteoclasts, and resorption pits are formed on
      the dentin slices. Addition of heparin, various glycosaminoglycans, and
      chemically modified heparins to the coculture reveals that heparin enhances the
      pit-forming activity of osteoclasts, and this effect of heparin on the activation
      of osteoclasts is dependent on its sugar chain structure. By contrast, mRNA
      expression levels of RANKL, RANK, and OPG in the coculture are not altered by
      heparin treatment. Furthermore, neither RANK nor RANKL binds to heparin,
      suggesting that heparin does not directly interact with these proteins. Instead,
      heparin specifically binds to OPG and prevents OPG-mediated inhibition of
      osteoclastic bone resorption in the coculture. Heparin treatment does not enhance
      osteoclastic bone resorption in a monoculture of osteoclasts derived from bone
      marrow cells, and in the coculture using osteoblasts from OPG-deficient mice. A
      (125)I-OPG binding assay showed that OPG binds to osteoblasts and that this
      binding is inhibited by the addition of heparin, suggesting that OPG binds to
      RANKL on the osteoblast membrane and that heparin blocks this interaction. These
      results demonstrate that heparin enhances osteoclastic bone resorption by
      inhibiting OPG activity.

PMID- 17560186
TI  - Pro- and antiapoptotic signalling. Proceedings from the 3rd International
      Conference of the Collaborative Research Center Experimental Hepatology,
      Dusseldorf, Germany, October 13-14, 2006.

PMID- 17560187
TI  - Triple fistula: management of a double tracheoesophageal fistula with a third H
      type proximal fistula.
AB  - Esophageal atresia (EA) with or without tracheoesophageal fistula (TEF) is a
      relatively common congenital condition in which there have been several described
      anatomical variants. The most common type, EA with distal TEF, comprises more
      than 75% of cases in many reports. Less commonly, a smaller proximal pouch
      fistula (H-type) will be associated with this most common variant in 1.4% of
      these cases. Only 2% of all cases of EA/TEF will have 2 large fistulas between
      the trachea and esophagus in which the end of the upper esophageal pouch connects
      terminally to the midtrachea and the distal esophagus arises from the trachea
      near the carina. Here we describe the management of an infant with this type of
      EA/TEF who was also found to have an H-type TEF of the proximal trachea. The
      combination of this type of EA/TEF with an associated H-type TEF or "triple
      fistula" has been previously described in the literature in only 1 other patient.

PMID- 17560188
TI  - Progress over 32 years of a survivor of giant exomphalos and outcome of
      pregnancy.
AB  - We report the progress of a female survivor of ruptured giant exomphalos over 32
      years. Two-stage repair was performed at birth, resulting in a giant ventral
      hernia, which was repaired at 31 months. She developed gross benign ascites at 24
      years, not previously described in association with congenital abdominal wall
      defects. This was associated with a misleading radiologic finding of a complex
      ovarian cyst and led to laparotomy. There were dense adhesions. Benign ascites
      and loculated pelvic fluid were drained, but the ovaries appeared healthy. A
      further laparotomy was performed for acute abdominal pain 2 years later. She
      subsequently had a successful pregnancy complicated by urinary retention. The
      abdomen expanded without difficulty, unlike the only other such case reported in
      the literature. A healthy baby girl was delivered by cesarean section at 37
      weeks' gestation, which was necessary because of a footling breech presentation.

PMID- 17560189
TI  - Mesenteric plexiform neurofibroma in an 11-year-old boy with von Recklinghausen
      disease.
AB  - We experienced the case of an 11-year-old boy diagnosed as having type 1
      neurofibromatosis with intraabdominal and pelvic masses. On physical examination,
      there were multiple cafe-au-lait spots larger than 15 mm in diameter scattered
      over the patient's entire body and axillary freckling, but no cutaneous
      neurofibromas were present. Lisch nodules were detected in the iris by a slit
      lamp. A large, firm mobile mass was palpated in the lower abdomen. Abdominal
      computed tomographic scan showed the hypodense masses in the lower abdomen and
      pelvic cavity. At laparotomy, a 16 x 9-cm, firm nodular mass along the mesentery
      of the terminal ileum and ascending colon was found. The mesenteric mass was
      encasing the superior mesenteric vessels and extending into the serosa of the
      intestine. The mass was incompletely excised together with affected intestine.
      However, resection of the rectum could not be performed because of the extensive
      involvement of the entire mesorectum. Histopathologic study revealed a plexiform
      neurofibroma involving the mesentery and intestine without evidence of malignant
      transformation. The postoperative course was uneventful. Ten months after the
      operation, a magnetic resonance imaging showed no interval change of the
      mesorectal mass.

PMID- 17560190
TI  - Choledocholithiasis in a 4-month-old infant.
AB  - Cholelithiasis is increasingly being diagnosed in newborns and infants because of
      the more frequent use of abdominal ultrasound. However, common bile duct stones
      causing obstruction or symptoms in infancy are exceedingly rare and are not often
      reported in the literature. We report the successful treatment of symptomatic
      choledocholithiasis in a 4-month-old patient with endoscopic retrograde
      cholangiopancreatography and endoscopic sphincterotomy.

PMID- 17560191
TI  - Actinomycosis: a differential diagnosis for appendicitis. A case report and
      review of the literature.
AB  - Actinomyces is a genus of gram-positive anaerobic or microaerophilic bacteria
      that colonize the upper respiratory and gastrointestinal tracts and the female
      genital tract. These organisms cause disseminated disease in the mouth, the
      respiratory system, and rarely in the gastrointestinal tract. The diseases
      produced by Actinomyces species result from the disruption of the barriers that
      allow the dissemination of the bacteria through the surrounding tissues. The
      appendix is often a nidus of Actinomyces infection, but a prompt diagnosis cannot
      be made without the results of histologic examination of the appendix. The
      treatment of choice for actinomycosis of the appendix is the high-dose parenteral
      administration of penicillin G for 2 weeks immediately after the diagnosis has
      been made and continued oral treatment with that agent for at least the next 6
      months. We present the case of a 13-year-old adolescent boy with actinomycosis of
      the appendix that was identified by histologic examination after appendectomy.

PMID- 17560192
TI  - Clinical features and HLXB9 gene mutation of a sporadic Chinese Currarino's
      syndrome case.
AB  - BACKGROUND/PURPOSE: The Currarino's syndrome (CS), which is characterized by
      sacral bony anomalies, anorectal malformation, and a presacral mass, is
      associated with mutations of HLXB9 gene. The aim of this study was to clearly
      define the clinical manifestations and molecular anomalies of CS in China.
      METHODS: We studied the medical history and clinical manifestations of a child
      with presacral mass. Genomic DNA was extracted from lymphocytes, and mutation
      analysis of the HLXB9 gene was conducted by using polymerase chain reaction and
      direct sequencing in the child and her parents. RESULTS: A previously unreported
      heterozygous missense mutation of HLXB9 gene was detected in the child.
      CONCLUSIONS: The HLXB9 gene mutation could take place in sporadic cases of CS
      without a typical hemisacrum.

PMID- 17560193
TI  - Foregut duplication cyst of the hypopharynx: a rare cause of upper airway
      obstruction.
AB  - Foregut duplication cysts of the hypopharynx are extremely rare, and only 6
      cases, all of which have been described as solid lesions and contained
      heterotopic gastric epithelium, could be found during our literature review. We
      present a unique case of a hypopharyngeal foregut duplication cyst that was
      grossly cystic and had no heterotopic epithelium microscopically. The present
      case required intubation for stridor and airway obstruction shortly after birth.
      Congenital laryngeal cysts can appear similar to this lesion. However, the
      hypopharyngeal location of a cyst is a clue for the diagnosis of duplication on
      endoscopic examination.

PMID- 17560194
TI  - Potential hazards of contrast study diagnosis of esophageal atresia.
AB  - Delay in the diagnosis of esophageal atresia (EA) is rare. We present a child
      with EA and distal tracheoesophageal fistula who was diagnosed 9 days from birth
      after a contrast study performed at the referring hospital. This article aims to
      highlight the potential hazards of using contrast to diagnose EA.

PMID- 17560195
TI  - Stephen L. Gans Distinguished Overseas Lecture. The neural crest in pediatric
      surgery.
AB  - AIM: This review highlights the relevance of the neural crest (NC) as a
      developmental control mechanism involved in several pediatric surgical conditions
      and the investigative interest of following some of its known signaling pathways.
      METHODS: The participation of the NC in facial clefts, ear defects, branchial
      fistulae and cysts, heart outflow tract and aortic arch anomalies, pigmentary
      disorders, abnormal enteric innervation, neural tumors, hemangiomas, and vascular
      anomalies is briefly reviewed. Then, the literature on clinical and experimental
      esophageal atresia-tracheoesophageal fistula (EA-TEF) and congenital
      diaphragmatic hernia (CDH) is reviewed for the presence of associated NC defects.
      Finally, some of the molecular signaling pathways involved in both conditions
      (sonic hedgehog, Hox genes, and retinoids) are summarized. RESULTS: The
      association of facial, cardiovascular, thymic, parathyroid, and C-cell defects
      together with anomalies of extrinsic and intrinsic esophageal innervation in
      babies and/or animals with both EA-TEF and CDH strongly supports the hypothesis
      that NC is involved in the pathogenesis of these malformative clusters. On the
      other hand, both EA-TEF and CDH are observed in mice mutant for genes involved in
      the previously mentioned signaling pathways. CONCLUSIONS: The investigation of NC
      related molecular pathogenic pathways involved in malformative associations like
      EA-TEF and CDH that are induced by chromosomal anomalies, chemical teratogens,
      and engineered mutations is a promising way of clarifying why and how some
      pediatric surgical conditions occur. Pediatric surgeons should be actively
      involved in these investigations.

PMID- 17560196
TI  - Toll-like receptor 4 plays a role in macrophage phagocytosis during peritoneal
      sepsis.
AB  - BACKGROUND: Peritoneal sepsis is a significant cause of mortality in infants with
      necrotizing enterocolitis, caused in part by impaired bacterial clearance. Recent
      studies have identified toll-like receptor-4 (TLR4) as a receptor for endotoxin
      (lipopolysaccharide [LPS]). We hypothesized that TLR4 regulates bacterial
      clearance from the peritoneal cavity and sought to investigate whether macrophage
      phagocytosis was involved. METHODS: Peritoneal sepsis was induced in mice
      expressing either functional TLR4 (TLR4-wild-type [WT]) or mutant TLR4 by
      intraperitoneal injection of either live Escherichia coli or LPS. Phagocytosis
      was assessed by measuring the uptake of opsonized red cells. To assess bacterial
      clearance, we irrigated peritoneal cavities of injected animals with saline and
      plated it on gram-negative selective media. RESULTS: LPS significantly increased
      the rate of phagocytosis by peritoneal macrophages from TLR4-WT mice, but not in
      those from TLR4-mutant mice, suggesting a role for TLR4 in phagocytosis. LPS also
      increased the rates of phagocytosis in cultured macrophages expressing TLR4,
      confirming these findings. The yield of gram-negative bacteria obtained from the
      peritoneal cavities of septic TLR4-WT mice was greater than that from TLR4
      mutants, consistent with TLR4-dependent alterations in their septic course.
      CONCLUSIONS: We conclude that TLR4 plays a critical role in the response to
      intraperitoneal E. coli through effects on phagocytosis by macrophages,
      suggesting the possibility of using TLR4 as a therapeutic target in diseases of
      peritoneal sepsis.

PMID- 17560197
TI  - Failure in the nonoperative management of pediatric ruptured appendicitis:
      predictors and consequences.
AB  - INTRODUCTION: The initial nonoperative management of perforated appendicitis
      fails in 15% to 25% of children. These children have complications and increased
      hospitalization. The purpose of this study was to identify predictors of failure.
      METHODS: Children with perforated appendicitis treated with antibiotics and
      intent for nonoperative management over a 4-year period were reviewed. Seventy
      five children were identified and included in the study. Failure was defined as
      undergoing appendectomy before the initially planned interval. RESULTS: Nine
      (12%) of the patients required appendectomy sooner than initially planned. Age,
      presenting symptoms, physical examination findings, and white blood cell (WBC)
      count were similar in both success and failure groups. Absence of abscess and
      presence of appendicolith were both predictors of failure in a multivariate
      analysis, which included the presence of small bowel obstruction. The failed
      group had a longer median total length of stay (18 days [range, 4-67] vs 8 days
      [range, 4-31]; P = .002) and underwent 3 times as many computed tomography scans
      as successes (3 [range, 2-7] vs 1 [range, 0-5]; P < .001). CONCLUSION: Lack of
      abscess and presence of an appendicolith predict failure of nonoperative
      management of perforated appendicitis in children even when the effect of small
      bowel obstruction is accounted for. Children with these characteristics may
      benefit from alternative management strategies.

PMID- 17560198
TI  - Adhesive small bowel obstruction after appendectomy in children: comparison
      between the laparoscopic and open approach.
AB  - INTRODUCTION: Adhesive small bowel obstruction (SBO) is a common postoperative
      complication. Published data in the pediatric literature characterizing SBO are
      scant. Furthermore, the relationship between the risk of SBO for a given
      procedure is not well described. To evaluate these parameters, we reviewed the
      incidence of SBO after laparoscopic appendectomy (LA) and open appendectomy (OA)
      performed at our institution. METHODS: With institutional review board approval,
      all patients that developed SBO after appendectomy for appendicitis from January
      1998 to June 2005 were investigated. Hospital records were reviewed to identify
      the details of their postappendectomy SBO. The incidences of SBO after LA and OA
      were compared with chi2 analysis using Yates correction. RESULTS: During the
      study period, 1105 appendectomies were performed: 477 OAs (8 converted to OA
      during laparoscopy) and 628 LAs. After OA, 7 (6 perforated appendicitis) patients
      later developed SBO of which 6 required adhesiolysis. In contrast, a patient with
      perforated appendicitis developed SBO after LA requiring adhesiolysis (P = .01).
      The mean time from appendectomy to the development of intestinal obstruction for
      the entire group was 46 +/- 32 days. CONCLUSIONS: The overall risk of SBO after
      appendectomy in children is low (0.7%) and is significantly related to perforated
      appendicitis. Small bowel obstruction after LA appears statistically less common
      than OA. Laparoscopic appendectomy remains our preferred approach for both
      perforated and nonperforated appendectomy.

PMID- 17560199
TI  - Increasing prevalence of gastroschisis repairs in the United States: 1996-2003.
AB  - PURPOSE: Local and state registries have shown recent increases in the prevalence
      of gastroschisis in the United States and abroad. The purpose of this study was
      to use a nationally representative database to identify national trends in the
      prevalence of gastroschisis repairs. METHODS: Records of infants undergoing
      gastroschisis repair were identified in the Nationwide Inpatient Sample from 1996
      to 2003. Birth data were obtained from the National Center for Health Statistics
      and used to calculate the rate of procedures/live births stratified by US census
      region. Survey statistics were used to account for the sampling design of the
      Nationwide Inpatient Sample database. RESULTS: Between 1996 and 2003, a total of
      9459 gastroschisis repairs were performed in the United States (3 procedures for
      every 10,000 births). A significant increase in the population-based rate of
      these procedures was observed in each census regions and nationwide. A twofold
      higher procedure rate was observed in 2003 than in 1996 (rate ratio, 2.0; 95%
      confidence interval, 1.1-2.9; P < .001). No significant change in unadjusted
      hospital mortality was observed regionally or nationally. CONCLUSIONS: The
      population-based rate of gastroschisis repairs significantly increased regionally
      and nationwide between 1996 and 2003, paralleling recent trends described at the
      local and state level.

PMID- 17560200
TI  - Incidence of abdominal wall defects is related to surface water atrazine and
      nitrate levels.
AB  - BACKGROUND: Gastroschisis and omphalocele are congenital abdominal wall defects
      (AWD). Atrazine and nitrates are common agricultural fertilizers. METHODS: The
      Centers for Disease Control and Prevention natality data set was used to collect
      data for patients with AWD born between January 1990 and December 2002. Similar
      data were obtained from the Indiana State Department of Health. An estimated date
      of conception was calculated by birth date and gestational age. Surface water
      nitrate and atrazine levels for Indiana were collected from US Geological Survey
      data. Midwest was defined as Indiana, Illinois, Iowa, Ohio, and Nebraska.
      Statistical analysis was performed by chi2 test and Pearson correlation for P <
      or = .05. RESULTS: The Centers for Disease Control and Prevention identified 9871
      children with AWD in 1990 and in 1995-2001 of 35,876,519 live births (rate
      2.75/10(5)). In Indiana, 358 children from 1990-2001 had AWD of 1,013,286 live
      births (rate 3.53/10(5)). The AWD rate in Indiana was significantly higher than
      the national rate in 1996 (P = .0377), 1998 (P = .0005), and 2001 (P = .0365) and
      significantly higher than the Midwest rate in 1998 (P = .0104). Monthly
      comparison demonstrated a positive correlation of AWD rate and mean atrazine
      levels (P = .0125). CONCLUSION: Indiana has significantly higher rates of AWD
      compared with national rates. Increased atrazine levels correlate with increased
      incidence of AWD.

PMID- 17560201
TI  - Development and validation of a risk stratification index to predict death in
      gastroschisis.
AB  - BACKGROUND: Gastroschisis is a rare congenital anomaly, the improved surgical
      management of which has contributed to a survival rate greater than 90%.
      Development of an accurate risk stratification system to help identify the subset
      of patients at greatest risk for death may lead to further improvements in
      outcome. METHODS: Infants with gastroschisis were identified from 16 years of the
      National Inpatient Sample database and the Kids' Inpatient Database using the
      International Classification of Diseases, Ninth Revision, Clinical Modification
      procedure code 54.71 (repair of gastroschisis) and an age of less than 8 days.
      Logistic regression analysis determined which coexisting diagnoses were
      significantly associated with death. Odds ratios from the logistic regression
      model were simplified and used as weighting factors to create an additive index.
      The index was validated using the 2003 Kids' Inpatient Database data set.
      RESULTS: Intestinal atresia, necrotizing enterocolitis, rare cardiac anomalies,
      and lung hypoplasia were strongly associated with death and used to create a
      scoring system with a potential range of 0 to 10. Every point increase on the
      scale of gastroschisis risk stratification index is associated with a 95%
      relative increase in the likelihood of death. CONCLUSION: We have developed a
      novel index, which is superior to previous classification systems in identifying
      patients with gastroschisis who are at highest risk for death.

PMID- 17560202
TI  - Temporary abdominal vacuum-packing closure in the neonatal intensive care unit.
AB  - BACKGROUND: Temporary abdominal vacuum-packing (vac-pac) closure is well known in
      adult literature, yet has not been reported in infants. METHODS: A review of
      children in the neonatal intensive care unit who underwent vac-pac closure from
      2000 to 2006 was performed. RESULTS: During this time, 7 infants underwent vac
      pac closure after abdominal surgery. Median age was 39 days, with a median weight
      of 3.2 kg. Reasons for vac-pac included abdominal compartment syndrome (3),
      ongoing intraabdominal sepsis (1), anticipated second-look procedures (2), and
      abdominal observation after repair of congenital diaphragmatic hernia on
      extracorporeal membrane oxygenation (1). PaCO2 revealed a drop from a median
      preoperative level of 50.3 to 44.0 mm Hg postoperatively. Median preoperative
      urine output was 3.9 and 3.1 mL/(kg h) postoperatively. One patient died with an
      open abdomen from overwhelming Escherichia coli sepsis, and all surviving
      patients (85.7%) proceeded to definitive abdominal closure with the median time
      of vac-pac use being 4 days. CONCLUSION: Vac-pac closure in infants is a safe and
      effective method of temporary abdominal closure. The detrimental effects of
      intraabdominal hypertension as well as risk of hemorrhage after repair of
      congenital diaphragmatic hernia while on extracorporeal membrane oxygenation also
      make this an important technique for abdominal observation.

PMID- 17560203
TI  - High incidence of postoperative bowel obstruction in newborns and infants.
AB  - BACKGROUND: Postoperative bowel obstruction (PBO) plagues patients of all ages
      after intraabdominal surgery. We examined the incidence, risk factors, and the
      need for operative intervention of PBO. METHODS: We reviewed all children who
      underwent a laparotomy or laparoscopy. Parameters included age, diagnosis, type
      and number of procedures, complications, time interval to PBO, treatment of PBO,
      morbidity, and mortality. RESULTS: From 2001 to 2005, 2187 abdominal operations
      were performed. Overall, 61 patients (2.8%) developed a PBO; 43 (70.5%) required
      reoperation. Postoperative bowel obstruction was more common in patients younger
      than 1 year (28/601, 4.7%) compared with older children (33/1586, 2.1%; P = .01,
      beta = .80). In infants, PBO was not influenced by initial diagnosis (P = .26) or
      whether the initial operation was clean/clean-contaminated or contaminated/dirty
      (P = .12). In children older than 1 year, nonoperative treatment was more likely
      to be successful if PBO occurred within 12 weeks of initial operation (12/16 vs
      3/14; P = .01). In contrast, all but one infant (16/17) with early PBO required
      reoperation. CONCLUSION: The incidence of PBO is significantly higher in newborns
      and infants than in older children (who have rates comparable to those reported
      in adults). Infants are significantly more likely to require operative
      intervention, particularly if PBO occurs early after the initial operation.

PMID- 17560204
TI  - Rapid closure of midgestational excisional wounds in a fetal mouse model is
      associated with altered transforming growth factor-beta isoform and receptor
      expression.
AB  - BACKGROUND: Many pediatric diseases are characterized by excessive tissue
      contraction. Because of a poor understanding of contraction, few therapies exist.
      We developed a murine fetal excisional wound model of contraction and theorize
      that wound closure is associated with changes in transforming growth factor-beta
      (TGF-beta) expression. METHODS: Pregnant FVB mice underwent hysterotomy at
      midgestational (E15) or late-gestational (E18) ages. Three-millimeter excisional
      wounds were made in fetuses and harvested at 32 hours. Real-time polymerase chain
      reaction was performed for TGF-beta1, TGF-beta2, TGF-beta3, TbetaR-1, and TbetaR
      2 in wounds and normal skin and normalized to glyceraldehyde-3-phosphate
      dehydrogenase. Data were analyzed by paired t test (P < .05). H&E staining of
      wounds was performed. RESULTS: E15 wounds (80.5% +/- 4.4%) were smaller than E18
      wounds (10.4% +/- 10.5%; P < .001) at 32 hours. E15 wounds expressed higher
      levels of TGF-beta1 compared with normal skin (P = .001). TbetaR-2 levels were
      elevated in E15 and E18 wounds compared with their respective normal skin (P =
      .02, P = .01) and in E18 normal skin compared with E15 normal skin (P = .002).
      CONCLUSION: This study demonstrates that rapid midgestational wound closure in a
      murine model is associated with increased TGF-beta1 and TbetaR-2 expression.
      Elucidating the role of the TGF-beta pathways may lead to an improved
      understanding of wound contraction.

PMID- 17560205
TI  - Tissue engineering from human mesenchymal amniocytes: a prelude to clinical
      trials.
AB  - PURPOSE: The surgical treatment of congenital anomalies using tissues engineered
      from amniotic fluid-derived mesenchymal cells has been validated experimentally.
      As a prerequisite for testing the clinical feasibility of this therapeutic
      concept, this study was aimed to expand human mesenchymal amniocytes in the
      absence of animal products. METHODS: Human mesenchymal cells were isolated from
      amniotic fluid samples (n = 12) obtained at 20 to 37 weeks' gestation. Their
      phenotypic profiles and cell proliferation rates were compared during expansion
      under 2 different media, containing either fetal bovine serum or allogeneic human
      AB serum. Statistical analyses were by the 2-sided Wilcoxon signed rank test and
      linear regression (P < .05). RESULTS: Mesenchymal cells could be isolated and
      expanded at any gestational age. There was a greater than 9-fold logarithmic
      expansion of mesenchymal cells, with no significant differences in the overall
      proliferation rates based on serum type (P = .94), or gestational age (P = .14).
      At any passage, cells expanded for up to 50 days remained positive for markers
      consistent with a multipotent mesenchymal progenitor lineage, regardless of the
      medium used. CONCLUSIONS: Human mesenchymal amniocytes retain their progenitor
      phenotype and can be dependably expanded ex vivo in the absence of animal serum.
      Clinical trials of amniotic fluid-based tissue engineering are feasible within
      preferred regulatory guidelines.

PMID- 17560206
TI  - Epidermal growth factor receptor-directed enterocyte proliferation does not
      induce Wnt pathway transcription.
AB  - BACKGROUND: Epidermal growth factor receptor (EGFR) stimulation enhances
      intestinal adaptation after massive small bowel resection (SBR), measured by
      taller villi, deeper crypts, and augmented enterocyte proliferation. Min mice
      with constitutively active beta-catenin signaling demonstrate enhanced villus
      growth after SBR, suggesting a role for the Wnt pathway during adaptation.
      Because there is crosstalk between EGFR signaling and the Wnt pathway, we
      hypothesized that beta-catenin is modulated by EGFR-induced enterocyte
      proliferation. METHODS: Rat intestinal epithelial cells were stimulated with EGF
      and cytoplasmic to nuclear trafficking of beta-catenin was measured. Beta-catenin
      directed transcription was also tested via transfection with a TOP/FOP luciferase
      reporter. Downstream transcriptional target expression was measured in murine
      intestine after SBR. RESULTS: Epidermal growth factor-treated rat intestinal
      epithelial cells exhibited increased proliferation compared to serum-deficient
      cells in the face of no detectable accumulation of nuclear beta-catenin. The
      luciferase assay results showed minimal transcription activity in response to
      EGF. In vivo experiments revealed no significant difference in expression of beta
      catenin targeted genes in crypt enterocytes after SBR. CONCLUSIONS: The mechanism
      for EGFR-induced proliferation of enterocytes does not appear to involve a
      transcriptional role for beta-catenin. The effects of EGFR signaling on beta
      catenin-mediated cell adhesion remain to be investigated.

PMID- 17560207
TI  - Maternal microchimerism in biliary atresia.
AB  - BACKGROUND: The aim of this study was to determine the existence and extent of
      maternal microchimerism in the livers of biliary atresia (BA) patients. METHODS:
      Two series of investigations were performed based on the sex of our subjects.
      Subjects for series I were men, of which 6 had BA. Livers were analyzed using X
      and Y chromosome probes and fluorescent in situ hybridization. Subjects for
      series II were woman. Nine BA cases and their mothers were HLA typed (class I).
      Daughter livers were also tested for antibodies to maternal and other HLA. Two
      cases of neonatal hepatitis, 2 cases of Alagille syndrome, and 1 case of Byler
      syndrome acted as controls. RESULTS: All male BA livers were found to contain a
      mixture of cells with 1 and 2 X chromosomes (ie, XY or XX). All livers from male
      controls had only 1 X chromosome (ie, XY). All female BA subjects had varying
      intensities of antimaternal HLA class I (HLA-A) antibodies in their bile duct
      epithelium and hepatocytes (strong, 5; mild, 3; weak, 1). The liver from the
      female control did not display any antimaternal HLA class I antibodies (HLA-Ab).
      CONCLUSION: Our preliminary data appear to show that maternal microchimerism is
      present within the livers of patients with progressive postnatal type BA. We
      suggest that BA could in fact be a graft-vs-host disease masquerading as an
      autoimmune reaction triggered by maternal microchimerism, and we intend to pursue
      this hypothesis further to clarify the etiology of BA.

PMID- 17560208
TI  - Two-hit rat model of short bowel syndrome and sepsis: independent of total
      parenteral nutrition, short bowel syndrome is proinflammatory and injurious to
      the liver.
AB  - INTRODUCTION: Infants with short bowel syndrome (SBS) are at a high risk for
      infectious complications and liver failure. We hypothesized that SBS, independent
      of total parenteral nutrition, is a proinflammatory state that is magnified by
      sepsis. METHODS: Sprague-Dawley rats were divided into 2 groups: sham laparotomy
      (SH, n = 10) or 75% small bowel resection (n = 10). After 14 days, each group
      underwent a second sham laparotomy (SH/SH and SBS/SH) or cecal ligation and
      puncture, followed 16 hours later by cecal excision and peritoneal washout
      (SH/sepsis and SBS/sepsis). Animals were killed 56 hours later. RESULTS: The SBS
      rats had higher serum levels of interleukin (IL) 6 vs SH (355 +/- 99 vs 104 +/-
      71 pg/mL, P < .05). Liver injury scores were higher in SBS/sepsis compared with
      SBS/SH animals (3.7 +/- 0.7 vs 1.9 +/- 0.3, P < .05). Hepatic messenger RNA
      levels of IL-6 (12.8-fold change [FC]) and tumor necrosis factor alpha (5.65 FC)
      were elevated in SBS vs SH rats; and IL-6 (114 FC), tumor necrosis factor alpha
      (3.87 FC), and Toll-like receptor 4 (7.65 FC) were increased in SBS/sepsis
      compared with SH/sepsis animals. CONCLUSION: Our results suggest that SBS,
      independent of total parenteral nutrition, is a proinflammatory state and that
      sepsis induces an exaggerated proinflammatory cytokine response that may play an
      important role in liver damage and may be mediated by Toll-like receptor 4.

PMID- 17560209
TI  - Clinical implications and surgical management of intussusception in pediatric
      patients with Burkitt lymphoma.
AB  - BACKGROUND/PURPOSE: Intussusception as a presenting feature of Burkitt lymphoma
      may be associated with early stage disease, which is curable with less intensive
      therapy. We determined the incidence, presentation, stage, and outcome of
      children with Burkitt lymphoma presenting with intussusception. METHODS: The
      medical records of patients with Burkitt lymphoma treated at our hospital from
      1962 to 2005 were reviewed, and the patients presenting with intussusception were
      then further analyzed. RESULTS: Of 189 patients with primary abdominal Burkitt
      lymphoma, 33 (17.5%) presented with intussusception. Their median age at
      diagnosis was 10 years (range, 3-19 years). Most patients presented with
      abdominal pain (88%) and/or nausea/vomiting (42%). Twenty-three (70%) of these 33
      patients as compared with 10 of the other 156 patients with abdominal lymphoma
      could have complete resection of their tumor (P < .0001) and hence had low stage
      disease (stage II). Only 10 patients with intussusception had stage III (n = 7)
      or stage IV (n = 3) unresectable disease. Twenty-five of the patients remained
      alive in continuous complete remission for 3 months to 31 years (median, 14
      years). CONCLUSION: Pediatric patients with Burkitt lymphoma presenting with
      intussusception often have completely resectable disease and are older than
      general pediatric patients with intussusception.

PMID- 17560210
TI  - Prospective study of antibiotic protocols for managing surgical site infections
      in children.
AB  - PURPOSE: We adopted antibiotic (Ab) protocols for managing surgical site
      infections in children and assessed their effectiveness. METHODS: We used our
      protocols on 1313 children between 2004 and 2005. All wounds were monitored for
      30 days and classified as clean, clean-contaminated, contaminated, or dirty
      infected. Infections were defined as superficial, deep, or organ/space. A
      retrospective study involving 721 children who had surgery in 2003 was also
      performed. Chi2 statistical analysis was performed. RESULTS: Postprotocol, all
      Abs were administered accurately by anesthesiologists and infections developed in
      only 22 cases (1.7%): 0.2% (clean), 2.6% (clean-contaminated), 5.8%
      (contaminated), and 20.8% (dirty-infected), respectively; 21 were superficial or
      deep and 1 was organ/space. Age at surgery and sex did not influence incidence,
      neither did length of surgery for clean-contaminated, contaminated, and dirty
      infected wounds; clean wounds were excluded because all surgery was minor.
      Overall, incidence of infections was 1.2% for elective surgery and 4.5% for
      emergency surgery (P < .01). Preprotocol, only 67% had Ab and infections
      developed in 27 cases (3.7%), which is significantly higher than in postprotocol
      (P < .01). CONCLUSIONS: Accurate administration of Ab and careful supervision by
      an infection control team appear to be effective for preventing wound infections
      in children.

PMID- 17560211
TI  - Reoperations in Hirschsprung disease.
AB  - BACKGROUND: We sought to identify causes of preventable complications related to
      operations for Hirschsprung disease. METHODS: We reviewed the cases of 51
      patients with Hirschsprung disease who underwent a primary procedure elsewhere,
      had a complication, and were referred for reoperation. RESULTS: Thirty-five
      patients had 1 failed operation, 10 had 2, and 6 had 3. Initial operations were
      Soave (20), Duhamel (15), Swenson (5), transanal endorectal (4), myectomy (3),
      unknown (3), and laparoscopic Swenson (1). Thirty-one patients presented with a
      stoma. Patients without a stoma (20) had fecal impaction (8), recurrent
      enterocolitis (6), and fecal incontinence (6). None had both enterocolitis and
      incontinence. Reoperation was performed posterior sagittally (40) or transanally
      (5). Indications included stricture (21), megarectal Duhamel pouches (12),
      fistulae (11 [8 rectocutaneous, 2 rectourethral, and 1 rectovaginal]), pouchitis
      (2), and retained aganglionic bowel (8). After reoperation, 14 were continent, 11
      had a stoma (8 permanent), 6 had voluntary bowel movements but soiled
      occasionally, 6 received rectal irrigations to avoid enterocolitis, 6 were
      incontinent but clean with bowel management, and 2 were lost to follow-up.
      CONCLUSION: Stricture, megarectal pouch, fistula, and retained aganglionic bowel
      are preventable complications. Enterocolitis is partially preventable but can
      occur after a technically correct procedure. Fecal incontinence is a preventable
      complication likely because of anal canal damage.

PMID- 17560212
TI  - Validation of the Baylor Continence Scale in children with anorectal
      malformations.
AB  - BACKGROUND: Anorectal malformations (ARMs) often result in lifelong problems with
      defecation. There have been no studies performed to develop scoring systems in
      children with fecal incontinence following repair of ARM. This study was designed
      to develop and validate a tool (Baylor Continence Scale [BCS]) to measure social
      continence in children after surgical correction of ARMs. METHODS: The BCS is a
      23-question survey, was administered to children who have had repair of an ARM,
      children with enuresis, and normal children. RESULTS: Children in the ARM group
      had an average BCS score of 28.0, which was statistically different from an
      enuresis control group (16.5) and normal controls (11.5) (P < .05). A
      significantly greater proportion of children in the ARM group had higher Impact
      on Family Scores (>30) than either the enuresis or normal control group (P <
      .05). CONCLUSIONS: The BCS tool should be useful in prospective studies of
      interventions to improve incontinence after repair of an ARM. An important
      secondary result of this study was to demonstrate the effect on families of
      caring for a child with imperforate anus, even years after the repair.

PMID- 17560213
TI  - The use of fundoplication for prevention of apparent life-threatening events.
AB  - OBJECTIVE: Gastroesophageal reflux disease (GERD) is cited by many to be a common
      cause of apparent life-threatening events (ALTEs). However, there are few reports
      in the literature regarding the surgical treatment of GERD to prevent a recurrent
      ALTE. METHODS: A retrospective review of infants undergoing fundoplication
      between 2000 and 2005 for the prevention of another ALTE was undertaken.
      Preoperative, operative, and postoperative data as well as follow-up information
      were collected. RESULTS: During the study period, 81 patients underwent
      fundoplication after presenting with an ALTE. All but 3 patients (96.3%) had been
      treated with antireflux medication. Moreover, 71 infants (87.7%) were taking
      antireflux medication at the time of their ALTE. A significant number of infants
      (77.8%) were hospitalized with a second ALTE before referral for fundoplication.
      After fundoplication, only 3 patients (3.7%) experienced a recurrent ALTE during
      the follow-up period; 2 required a second fundoplication and 1 underwent
      pyloromyotomy. None of these 3 patients have experienced a recurrent ALTE after
      the second operation. The median follow-up has been 1738 days. CONCLUSION: Our
      data suggest that among patients who had an ALTE and are found to have GERD,
      fundoplication appears to be an effective method for preventing recurrent ALTE.

PMID- 17560214
TI  - The impact of managing moderately injured pediatric trauma patients without
      immediate surgeon presence.
AB  - PURPOSE: The purpose of this study was to determine the outcome of "minor
      resuscitation" trauma patients managed without the immediate presence of a
      surgeon. METHODS: In 2003, our hospital replaced surgeons with pediatric
      emergency medicine physicians for level 2 (minor resuscitation) trauma alerts,
      whereas the level 1 (major resuscitation) alerts remained surgeon directed. We
      compared patients treated in the 3 years before (period 1) and after (period 2)
      this change. Patient records were analyzed for discharges, alert upgrades, Injury
      Severity Score (ISS), time to destination, and mortality. RESULTS: There were 918
      admissions and 93 discharges in period 1 compared with 815 admissions and 652
      discharges in period 2. In period 1, 3% were upgraded to level 1 status compared
      with 9% in period 2 (P < .0001). The mean ISS of admitted patients and the
      percentage of critical (ISS >15) patients were greater in period 2 (P < .001).
      The time to inpatient floor was longer in period 2, but the elapsed times to
      operating room and to pediatric intensive care unit were not significantly
      different. CONCLUSION: Pediatric emergency medicine physicians discharged more
      patients than the surgeons, but also upgraded more to level 1 status. Level 2
      trauma patients can be safely managed without immediate surgeon presence.

PMID- 17560215
TI  - Disparities in child abuse mortality are not explained by injury severity.
AB  - BACKGROUND: Unadjusted abuse-related mortality has been demonstrated to be nearly
      4-fold higher for African American (AA) children. Little is known about the
      etiology of this disparity. This study examines the importance of injury severity
      and initial presentation in explaining the observed disparity. METHOD: Our trauma
      database was reviewed to identify all abused patients admitted over a 10-year
      period. Outcomes among white and AA children were compared with specific
      attention to injury severity scores and initial presentation. Logistic regression
      and Cox proportional hazard analyses were performed to evaluate the impact of
      race on outcome. RESULTS: There were 443 abused children identified. Thirty-eight
      percent of the group was AA. The overall mortality was 7.7%; however, the AA
      mortality was significantly higher than white children (14.8% vs 3.3%; P < .05).
      After controlling for injury severity and physiology at presentation, the odds
      ratio of mortality for an AA child was 9.14 (95% confidence interval, 1.97
      42.43). Survival analysis confirmed the disparity after revealing a hazard ratio
      of dying for AA children of 6.51 (95% confidence interval, 2.74-15.47) compared
      with white children. CONCLUSION: Despite attempts to control for the clinical
      presentation and injury severity of abused children, significant differences in
      mortality persist between AA and white children.

PMID- 17560216
TI  - Long-term outcome of nonoperative pediatric splenic injury management.
AB  - BACKGROUND: Nonoperative management (NOM) of blunt splenic trauma is the standard
      of care in hemodynamically stable children. The long-term risk of this strategy
      remains unknown. The object of this study was to investigate the incidence of
      long-term complications after NOM of pediatric splenic injury. METHODS: All
      children who underwent NOM for blunt splenic trauma over an 11-year period were
      identified. Patients were interviewed for any ailments that could be related to
      their splenic injury, and hospital data were analyzed. RESULTS: A total of 266
      patients were identified, and 228 patients (86%) were interviewed. Mean follow-up
      time was 5 +/- 3 years. One patient had a delayed complication, a splenic
      pseudocyst. Pain more than 4 weeks after injury was unusual. Time until return to
      full activity varied broadly. CONCLUSION: The incidence of long-term
      complications after NOM of pediatric splenic injury was 1 (0.44%) in 228
      patients. Nonoperative management of pediatric blunt splenic trauma in children
      is associated with a minimal risk of long-term complications.

PMID- 17560217
TI  - Pediatric trauma care: a profitable enterprise?
AB  - PURPOSE: We set out to examine whether pediatric trauma care resulted in a
      financial burden. METHODS: We reviewed financial data for children with an
      International Classification of Diseases, Ninth Edition, injury diagnosis code
      over 2 years at an urban level I pediatric trauma center. We divided inpatients
      into length of stay categories, and profit or loss was calculated for each
      payor/length of stay category. These figures were then used to estimate revenue
      for each hospital based upon their patients payor/length of stay distribution
      that was obtained from the KID database. Our payor-based outpatient revenue
      figures were also applied to the other hospital-calculated outpatient visits to
      obtain an estimate of their outpatient revenues. RESULTS: We treated 49,437
      injured children with a revenue balance of more than $8 million. Commercial
      insurance resulted in a positive revenue stream. Losses increased as length of
      stay increased for patients with Medicaid or self-pay. Outpatient encounters
      resulted in 59% of the revenue. Extrapolating our data, 84% of pediatric trauma
      centers in 27 states generate an average of $800,000 revenue. CONCLUSIONS:
      Pediatric trauma care is a profitable enterprise. Inadequate reimbursement
      remains for Medicaid and self-pay patients, which could result in financial
      losses should this proportion of the patient mix be more than 55%.

PMID- 17560218
TI  - The split abdominal wall muscle flap repair for large congenital diaphragmatic
      hernias on extracorporeal membrane oxygenation.
AB  - BACKGROUND: Numerous techniques exist for repairing large congenital
      diaphragmatic hernias (CDHs) including prosthetic patches, tissue-engineered
      grafts, and various muscle flaps. A split abdominal wall muscle flap is a simple,
      durable way to repair a large diaphragmatic hernia. This technique has not gained
      widespread use, and some have suggested that it would be inappropriate in the
      setting of extracorporeal membrane oxygenation (ECMO) because of bleeding risk.
      We present our series of diaphragmatic hernias with a focus on those repaired
      with the split abdominal wall technique while on ECMO. METHODS: A retrospective,
      single-institution chart review was performed on all patients who underwent
      surgical repair for CDH over 6 years beginning in August 2000. RESULTS: Seventy
      five patients underwent repair. Sixteen were performed with patients on ECMO. Of
      these, 4 were closed primarily, 7 used a prosthetic patch, and 5 used a split
      abdominal wall muscle flap. Two patients in the prosthetic group developed a
      recurrent hernia, and 2 required reoperation for bleeding while on ECMO. No
      reoperations for bleeding were required in the abdominal muscle flap group.
      CONCLUSIONS: The split abdominal wall muscle flap can be safely performed on
      anticoagulated patients. We believe it is a practical option for repairing large
      CDHs.

PMID- 17560219
TI  - Approaches to neurodevelopmental assessment in congenital diaphragmatic hernia
      survivors.
AB  - BACKGROUND: Infants with congenital diaphragmatic hernia require complex surgical
      care and may have neurodevelopmental morbidity. We examined the performance of
      reports of motor functioning in 25 congenital diaphragmatic hernia survivors
      using the parent-completed Developmental Profile-II and a clinical evaluation by
      a neurodevelopmental pediatrician (MD) measured against the Bayley motor scale.
      METHODS: Bayley motor scores were dichotomized as normal or abnormal. Sensitivity
      and specificity were calculated for each test. RESULTS: The median age at
      assessment was 25 months. Bayley motor scores were abnormal in 77% of infants
      tested (10/13). The MD examinations detected motor problems in 92% (12/13).
      Sensitivity and specificity of the MD examination were 1.0 and 0.33,
      respectively. Developmental Profile-II physical scores were abnormal in 15%
      (2/13); sensitivity and specificity were 0.2 and 1.0, respectively. CONCLUSIONS:
      The high rate of abnormal motor findings in this study supports the need for
      ongoing screening and evaluation. The sensitivity of MD examinations was
      excellent, but hypotonia findings were not universally corroborated by the
      Bayley. Although specificity of parent-reported motor findings was high, parents
      underreported abnormal motor findings. Parental reports of neurodevelopmental
      problems should be heeded, and physicians should perform screening motor
      examinations. Bayley assessments may be warranted to determine the functional
      implications of observed abnormalities.

PMID- 17560220
TI  - Thoracoscopic versus open resection of congenital lung lesions: a case-matched
      study.
AB  - PURPOSE: The purpose of the study was to compare the outcomes in children
      undergoing thoracoscopic versus open resection of congenital lung lesions.
      METHODS: Retrospective review of 12 consecutive children (<3 years of age)
      undergoing thoracoscopic resection of a congenital lung lesion between 2004 and
      2005 was performed. Intraoperative and early postoperative results were compared
      with randomly selected age- and sex-matched (2:1) patients undergoing thoracotomy
      between 2000 and 2005. RESULTS: Twelve children underwent thoracoscopic resection
      and were compared with 24 that underwent thoracotomy. Seventy five percent of the
      lesions in both groups were congenital cystic adenomatoid malformations. There
      were no major intraoperative complications. Two thoracoscopic procedures were
      converted to a thoracotomy. Perioperative outcomes including operative time,
      length of stay, duration and volume of chest tube drainage, and dose and duration
      of intravenous opioids were similar for the procedures. However, children
      undergoing thoracoscopic procedures were less likely (odds ratio = 0.07) to have
      received adjunctive regional anesthesia. Overall morbidity was 33% thoracoscopic
      and 25% open (P = .70). CONCLUSION: Thoracoscopic resection is a safe and
      feasible alternative to open resection of congenital lung lesions. Examination of
      long-term advantages of the thoracoscopic approach such as decreased risk of
      chest wall deformity and scoliosis and improved cosmesis will require longer
      follow-up.

PMID- 17560221
TI  - Changes in intestinal motility and in the myenteric plexus in a rat model of
      intestinal ischemia-reperfusion.
AB  - BACKGROUND/PURPOSE: Early histologic changes induced by intestinal ischemia
      reperfusion injury (IIRI) have been extensively studied using animal models.
      However, information regarding late effects on intestinal motility is lacking.
      The aim of this study was to investigate the late effects of IIRI on myenteric
      plexus histology and intestinal motility. MATERIALS AND METHODS: Thirty-two
      postweaning male rats weighing between 58 and 103 g were divided randomly into 4
      groups: Control (unoperated), Sham (celiotomy), 30-minute ischemia (celiotomy and
      superior mesenteric artery ischemia for 30 minutes), and 45-minute ischemia
      (celiotomy and superior mesenteric artery ischemia for 45 minutes). Postoperative
      intestinal motility was assessed by weighing total fecal output for 24 hours on
      the 3rd, 7th, 14th, and 21st day after surgery. Segments of duodenum, jejunum,
      and ileum were examined at light microscopy for changes in the myenteric plexus.
      RESULTS: Three weeks after IIRI, the ganglion cells from the myenteric plexus
      appeared in light microscopy, spongy or foamy, containing many vacuoles in their
      cytoplasm. The neuronal nucleus became irregular, with degenerative signs. These
      alterations did not occur among animals from the control or sham groups. Although
      the animals of the 45-minute ischemia group showed a significant drop in fecal
      output in the 21st postoperative day, this appeared to have no effect on weight
      gain. CONCLUSIONS: The results suggest that intestinal ischemia-reperfusion
      causes late neuronal damage. These changes resulted in alterations of intestinal
      motility, which, within the conditions of the present study, had no repercussion
      on general weight gain.

PMID- 17560222
TI  - Predicting the need for fundoplication at the time of congenital diaphragmatic
      hernia repair.
AB  - PURPOSE: This study was conducted to examine the preoperative factors predictive
      of subsequent intervention for gastroesophageal reflux (GER) in children with
      congenital diaphragmatic hernia (CDH). METHODS: We conducted a retrospective
      cohort study on children who underwent repair of a CDH between January 1, 1995,
      and December 31, 2002 with follow-up continuing to September 1, 2005. Excluded in
      the study were children who died during their first admission, or who underwent
      fundoplication at the time of CDH repair. Univariate and multivariate logistic
      regressions were performed to examine preoperative factors predictive of
      subsequent intervention (fundoplication or gastrojejunal tube placement).
      RESULTS: Of 86 children, 13 underwent intervention (fundoplication, 10;
      gastrojejunal tube, 3) for GER. Univariate predictors included the following:
      right-sided CDH, use of nonconventional ventilation, liver within the chest, and
      patch closure of the CDH. However, only liver within the chest and patch closure
      of the CDH were significant predictors in a multiple variable analysis. The
      positive and negative predictive values of the multivariate model were 69.2% and
      87.7%, respectively. CONCLUSIONS: Infants with CDH who have liver within the
      chest or require patch closure of their hernia are at increased risk for
      subsequent intervention for GER. These children may represent a subpopulation
      that would benefit from fundoplication at the time of CDH repair.

PMID- 17560223
TI  - Single-port laparoscopic appendectomy conducted intracorporeally with the aid of
      a transabdominal sling suture.
AB  - BACKGROUND/PURPOSE: Laparoscopic appendectomy (LA) is becoming popular for the
      treatment of acute and perforated appendicitis. Since it was first described, LA
      has been modified various times. We present the results of a new technique of LA
      conducted through a single port without exteriorizing the appendix to perform the
      operation. MATERIALS AND METHODS: Single-port LA was attempted in 38 patients (23
      boys, 15 girls). Under general anesthesia, an 11-mm port with two 5-mm working
      channels or an 11-mm port through which a 10-mm scope (0 degrees) with a parallel
      eyepiece and a 6-mm working channel was inserted through the umbilicus. The
      appendix was grasped and dissected from the surrounding tissues with a single
      dissector or grasper. With a percutaneously inserted suture from the right lower
      quadrant into the peritoneal cavity, the appendix was pulled toward the abdominal
      wall after passing the suture through the mesoappendix. After mesenteric
      dissection with hook cautery, the base of the appendix was ligated with 2-0
      polyglactin with a fisherman knot. The appendix was withdrawn into the trocar and
      extracted from the abdomen together with the trocar. RESULTS: Laparoscopic
      appendectomy was completed in 35 patients through a single port. A second port
      insertion was required in 3 patients. No peroperative and postoperative
      complications were encountered. Average duration of the procedure was 38 +/- 5.6
      minutes. CONCLUSION: This unique method further improves the minimal invasiveness
      of LA because a single port is used. Single-port intracorporeal appendectomy
      procedure is a safe, highly minimal invasive procedure with excellent cosmetic
      results.

PMID- 17560224
TI  - Primary pull-through with modified Duhamel technique: 1 institution's experience.
AB  - BACKGROUND/PURPOSE: Primary pull-through for Hirschsprung disease has been
      reported to give comparable surgical outcomes to staged operations with less
      morbidity. The aim of this study was to review the early experiences in our
      institution with the primary pull-through option. METHODS: Medical records of 50
      consecutive patients with Hirschsprung disease who underwent a modified Duhamel
      pull-through operation from 2001 to 2004 were retrospectively reviewed. For
      analysis, cases were divided into 2 groups: primary pull-through (group I, 30
      patients), and patients with a previously established colostomy who underwent a
      staged operation (group II, 20 patients). Comparisons were made regarding
      operating time, operative morbidity, and medium-term functional outcomes.
      RESULTS: There was no difference between the groups with respect to median age
      and weight at time of surgery, sex ratio, presenting symptoms, and extent of
      aganglionosis. Seventy-four percent of the procedures were performed on infants
      (group I, 21 [70%] of 30 patients; group II, 16 [80%] of 20 patients). Acute
      postoperative complications were experienced by 4 (13.3%) of 30 patients in group
      I and 4 (20%) of 20 patients in group II (P <.05). Postoperative enterocolitis
      occurred in 11 (36.7%) of 30 patients in group I and in 7 (41.2%) of 17 patients
      in group II. CONCLUSIONS: Our experience indicates that the primary pull-through
      using a modified Duhamel technique gave neither difference in functional outcomes
      nor medium-term complications compared to a staged procedure. Considering a
      sparing of colostomy and a potential economic benefit, the procedure should be
      considered in selected patients.

PMID- 17560225
TI  - Ncx (Enx, Hox11L.1) is required for neuronal cell death in enteric ganglia of
      mice.
AB  - BACKGROUND/PURPOSE: Ncx (Enx, Hox11L.1)-deficient (Ncx-/-) mice develop mega-ileo
      ceco-colon with a larger number of neuronal cells in the enteric ganglia. We
      investigated mechanisms related to this abnormality and directed our attention to
      the effects on gastrointestinal tract functions. METHODS: The number of NADPH
      diaphorase or cuprolinic blue-positive neuronal cells in the enteric ganglia was
      examined during growth of the mice. Neuronal cell death of enteric ganglia was
      assayed by terminal deoxynucleotidyl transferase-mediated deoxyuridine
      triphosphate-biotin nick end labeling. Function of the gastrointestinal tract was
      determined by measuring excretion time of the barium chloride given into the
      stomach. RESULTS: The number of neuronal cells decreased in control mice older
      than 2 weeks, and neuronal cell death was evident in the ganglia. However, the
      number of neuronal cells did not decrease in Ncx-/- mice, and cell death was
      rare. Excretion time of barium chloride was prolonged in all Ncx-/- mice examined
      and was improved by the administration of an inhibitor of nitric oxide synthase.
      CONCLUSIONS: Ncx participates in cell death of enteric neurons. Motor abnormality
      of the gastrointestinal tract in Ncx-/- mice may be attributed to the large
      number of neuronal cells.

PMID- 17560226
TI  - Advantages of intraoperative semiquantitative evaluation of myenteric nervous
      plexuses in patients with Hirschsprung disease.
AB  - BACKGROUND: The reappearance of an occlusive syndrome after surgical treatment of
      patients with Hirschsprung disease is often caused by incomplete resection of the
      affected segment. Intraoperative examination of frozen biopsies assists surgery,
      but interpretation of biopsies in the transitional zone is difficult. METHODS: We
      performed retrospective semiquantitative evaluations of myenteric nervous
      plexuses at the proximal limits of resection specimens from 41 children who were
      treated for rectocolic Hirschsprung disease using intraoperative examination of
      transparietal biopsies. The results of the evaluations were correlated with the
      postoperative courses of the children. RESULTS: After formalin fixation, the mean
      length of the aganglionic segments was 8.9 cm (range, 1-37.5 cm). At the proximal
      limit, the percentage of the circumference of the muscularis propria that was
      composed of plexuses with ganglion cells was more than 95% in 7 children, 90% to
      95% in 21 children, 40% to 80% in 6 children, and 30% or less in 7 children
      (17%), 4 of whom subsequently developed occlusive syndromes. CONCLUSIONS:
      Semiquantitative intraoperative examination of the entire circumference of
      resected segments facilitates precise evaluation of intrinsic innervation at the
      level of the anastomosis and may reduce the frequency of recurrence of occlusive
      symptoms after surgery.

PMID- 17560227
TI  - Treatment of fistula-in-ano in infants with a seton.
AB  - Anal fistula in infants is a common disease. Although many are recovered by
      conventional treatment, there are some patients who are not repaired easily. We
      performed the seton method to an anal fistula and report the good result that we
      obtained.

PMID- 17560228
TI  - Watson fundoplication in children: a comparative study with Nissen
      fundoplication.
AB  - BACKGROUND: Nissen fundoplication is the gold standard antireflux procedure in
      children. In 1996, one pediatric surgeon adopted the anterior fundoplication
      described by Watson in 1991. This procedure is reported to achieve good reflux
      control while permitting burping, active vomiting, and reducing gas bloat. An
      audit project was undertaken to compare the clinical outcome of children
      undergoing Nissen and Watson fundoplication. METHODS: The case notes of 144
      children undergoing open fundoplication between February 1995 and February 2002
      were reviewed retrospectively. RESULTS: Results of 72 boys and 59 girls
      comprising 76 Nissen and 55 Watson fundoplications were assessed. In each group,
      one death occurred within 1 month of operation. Chest infections occurred in 6.6%
      (Nissen) and 1.8% (Watson), and wound infections in 2.6% and 1.8%, respectively.
      Dysphagia was recorded in 7.9% of Nissen and 1.8% of Watson fundoplications.
      Follow-up data were analyzed in 70 children with Nissen and 48 children with
      Watson fundoplication. When overall clinical outcome was assessed for those
      patients with a minimum follow-up of 1 year, 85.1% Nissen and 88.2% Watson were
      judged good/excellent; 14.9% Nissen and 11.8% Watson were judged poor/bad.
      CONCLUSION: Watson fundoplication can safely be performed in children with
      comparable clinical outcome to Nissen fundoplication.

PMID- 17560229
TI  - Primary anorectoplasty in females with common anorectal malformations without
      colostomy.
AB  - BACKGROUND/PURPOSE: The objective of this study is to assess the feasibility of
      primary posterior sagittal anorectoplasty in vestibular fistula without a
      covering colostomy. METHODS: Girls presenting from July 1997 to July 2005 with
      vestibular fistula were included prospectively in the study, in a nonrandomized
      manner, after excluding those with megarectosigmoid and pouch colon. All
      underwent primary posterior sagittal anorectoplasty after total gut irrigation
      with normal saline. They were kept nil per oral until the fifth postoperative
      day. No patient was started on anal dilatation. Patients were assessed for
      immediate and delayed complications as well as voluntary bowel movements and
      continence. RESULTS: A total of 72 patients with an age range of 1.5 months to 8
      years (median, 9 months) were studied after excluding 7 with pouch colon and 3
      with megarectosigmoid. Of the 72, 3 had undergone previous surgery. Follow-up
      ranged from 7 months to 8 years. No wound dehiscence or recurrence of fistula was
      noted. There were 5 mild wound infections. At 1 month postoperative, all patients
      had 1 to 3 stools per day with no episodes of soiling. None required anal
      dilatations, laxatives, or enemas. CONCLUSIONS: Primary posterior sagittal
      anorectoplasty in vestibular fistula can be performed without a covering
      colostomy provided fecal contamination of the wound can be kept to the minimum in
      the first postoperative week. We achieve this by thorough total gut irrigation
      preoperatively and keeping the child nil per oral for the first 5 postoperative
      days. Continence rates are excellent and postoperative constipation is unlikely
      if megarectosigmoid and pouch colon are ruled out before surgery. Anal dilatation
      is not required after surgery.

PMID- 17560230
TI  - Hepatobiliary scintigraphy after Kasai procedure for biliary atresia: clinical
      correlation and prognostic value.
AB  - BACKGROUND/PURPOSE: Kasai portoenterostomy (KP) is regarded as first-line
      treatment for biliary atresia, although its postoperative course is often
      unpredictable. Hepatobiliary scintigraphy using technetium-labeled iminodiacetic
      acid derivatives offers a dynamic, objective assessment both of parenchymal liver
      function and restored biliary excretion. The value of postoperative radionuclide
      scans was assessed prospectively in a large population of post-KP infants.
      METHODS: Radionuclide scans consisted of an intravenous dose of 20 MBq of 99mTc
      mebrofenin iminodiacetic acid and subsequent gamma camera imaging. Four scan
      variables were evaluated: the hepatic extraction fraction (HEF; ie, initial liver
      uptake divided by the peak vascular uptake), the half-life of tracer excretion
      (TEX), the shape of the excretion curve, and the presence of activity in the Roux
      loop at 4 hours postinjection. All infants had type 3 biliary atresia with a
      median age at KP of 59 days (24-120 days). To assess predictive value, outcome
      (clearance of jaundice and need for transplant) was assessed at 6 months (for 1
      week scan) and 2 years (for 6-month scan). RESULTS: Eighty-seven infants
      underwent a radionuclide scan at 1 week post-KP. The median HEF was 34% (10%
      90%). No relationship could be identified between HEF (P = .2) or excretion curve
      shape (P = .9) and outcome (at 6 months), and there were too few examples of a
      measurable TEX to allow meaningful comparison. The only predictive element at
      this time point was Roux loop activity (positive predictive value, 79%; negative
      predictive value, 53%; for "good" isotope bowel activity). Forty-four infants
      completed a second scan at 6 months. Median HEF increased from a baseline of 37%
      (11%-90%) to 64% (8%-100%) (P < .0001), although there was no significant
      intercorrelation (P = .12). The most predictive variables (of outcome at 2 years)
      were curve shape (positive predictive value, = 95%, negative predictive value,
      82%) and TEX, and the least predictive was now Roux loop activity. CONCLUSIONS:
      Early (at 7 days) hepatic scintigraphy is not predictive of poor outcome in
      general, although Roux loop activity does indicate later success. Later hepatic
      scintigraphy (at 6 months) allows a detailed assessment of dynamic liver function
      with biliary excretion variables predictive of outcome in the medium term.

PMID- 17560231
TI  - Fecal impaction in children: report of 53 cases of rectal seed bezoars.
AB  - BACKGROUND: Rectal seed bezoars in children seem to present an uncommon problem
      that necessitates some operative intervention. PURPOSE: Our objective is to
      determine the occurrence and clinical characteristics of rectal seed bezoars in
      children with fecal impaction. METHODS: A retrospective review of hospital
      records of children with discharge diagnosis of fecal impaction was conducted
      from 1996 to 2005 in a university-affiliated general hospital RESULTS: The study
      group is composed 59 children. A total of 53 had rectal seed bezoars: watermelon
      seeds in 43 children, prickly pear seeds in 6, sunflower seeds in 3, and
      pumpkinseeds in 1. Six children had seedless fecal impaction. All the children
      with seed bezoars were of Arab origin. Fifty children were treated under general
      anesthesia. Of the remaining 9 children, 5 underwent digital disimpaction without
      general anesthesia: 3 with seedless feces and 2 with rectal seed bezoars. Four
      children with rectal seed bezoars evacuated spontaneously without digital
      disimpaction. There was summer seasonal preference for watermelon and prickly
      pear seed bezoars, whereas sunflower seed bezoars occurred in the spring.
      CONCLUSIONS: Fecal impaction owing to rectal seed bezoars is more common than
      previously believed. Its occurrence among Arab children alone in this study might
      indicate a high proportion of fecal seed bezoars throughout the Middle East. We
      propose that the preferred treatment should include disimpaction and irrigation
      of the rectal content under anesthesia. Greater awareness by primary care
      practitioners and parents might be beneficial in its prevention in the future.

PMID- 17560232
TI  - Outcomes after laparoscopic surgery in neonates with hypoplastic heart left heart
      syndrome.
AB  - BACKGROUND/PURPOSE: Laparoscopy has advanced the care of children for a variety
      of pediatric surgical diseases. However, complication rates for laparoscopic
      interventions in neonates with hypoplastic left heart syndrome (HLHS) have not
      been well described. The purpose of this study is to present the largest reported
      series of laparoscopic surgery performed in patients with HLHS. METHODS: We
      conducted a single-institution, retrospective chart review for all neonates with
      HLHS who underwent a laparoscopic procedure from September 2002 to March 2005.
      Data regarding patient characteristics, intraoperative monitoring, previous
      cardiac surgery, perioperative complications, and postoperative mortality were
      assessed. RESULTS: Twelve patients with HLHS underwent a total of 13 operations
      during the study period (8 combined Nissen fundoplication and gastrostomy tubes,
      3 isolated gastrostomy tubes, 1 Ladd procedure, and 1 combined Nissen
      fundoplication and gastrocutaneous fistula closure). All cases were completed
      laparoscopically. Patients had undergone palliative cardiac surgery but were not
      completely corrected; therefore, they were cyanotic. Perioperative complications
      were observed in 6 patients (3 gastrostomy tube site infections, 1 small bowel
      obstruction, 1 postoperative sepsis, and 1 urinary tract infection). There was no
      mortality in this series. CONCLUSIONS: From this experience, it appears that
      laparoscopy can be performed safely and with satisfactory outcomes in patients
      with HLHS. However, a multidisciplinary approach, including the availability of a
      skilled and experienced cardiac anesthesia team, is believed to be critical to
      optimize outcomes in these critically ill children.

PMID- 17560233
TI  - Long-term functional sequelae of sacrococcygeal teratoma: a national study in The
      Netherlands.
AB  - BACKGROUND: Long-term functional sequelae after resection of sacrococcygeal
      teratoma (SCT) are relatively common. This study determines the incidence of
      these sequelae associated clinical variables and its impact on quality of life
      (QoL). PATIENTS AND METHODS: Patients with SCT treated from 1980 to 2003 at the
      pediatric surgical centers in The Netherlands aged more than 3 years received age
      specific questionnaires, which assessed parameters reflecting bowel function
      (involuntary bowel movements, soiling, constipation), urinary incontinence,
      subjective aspect of the scar, and QoL. These parameters were correlated with
      clinical variables, which were extracted from the medical records. Risk factors
      were identified using univariate analysis. RESULTS: Of the 99 posted
      questionnaires, 79 (80%) were completed. The median age of the patients was 9.7
      years (range, 3.2-22.6 years). There were 46% who reported impaired bowel
      function and/or urinary incontinence (9% involuntary bowel movements, 13%
      soiling, 17% constipation), and 31% urinary incontinence. In 40%, the scar was
      cosmetically unacceptable. Age at completion of the questionnaire, Altman
      classification, sex, and histopathology were not risk factors for any long-term
      sequelae. Size of the tumor (>500 cm3) was a significant risk factor for
      cosmetically unacceptable scar (odds ration [OR], 4.73; confidence limit [CL],
      1.21-18.47; P = .026). Long-term sequelae were correlated with diminished QoL.
      CONCLUSION: A large proportion of the patients with SCT have problems with
      defecation, urinary incontinence, or a cosmetically unacceptable scar that
      affects QoL. Patients who are at higher risk for the development of long-term
      sequelae cannot be clearly assessed using clinical variables.

PMID- 17560234
TI  - Infarction of extralobar pulmonary sequestration after blunt trauma.
AB  - Pulmonary sequestration is a rare congenital lung malformation that occurs in
      either an intralobar or extralobar location and is generally asymptomatic. We
      report an unusual case of a child who presented with infarction of a previously
      asymptomatic extralobar pulmonary sequestration after blunt trauma, eventually
      requiring surgical excision.

PMID- 17560235
TI  - Innovative and cost-effective management of large omphalocele.
AB  - BACKGROUND/PURPOSE: The aim of this study was to develop a method of management
      of large omphalocele, with easily available inexpensive materials. The efficacy
      of using the plastic of urine collection bag and paper stapler, in creating the
      "silo" for the management of 3 newborns with such defects, were assessed.
      METHODS: All operations were done within 36 hours of birth. A silo was created
      with the plastic of a sterile urine collection bag, which was stapled with a
      paper stapler at its free margin. The omphalocele was gradually reduced every 24
      to 48 hours, using the stapler, until the contents were reduced, when the
      abdominal wall was repaired. RESULTS: The mean time taken to close the abdominal
      defect was 34 days. All patients could be breast-fed from 48 hours after the
      first stage is done. Rooming in was done by day 7. None of the babies required
      assisted ventilation. CONCLUSION: This method is simple and cost-effective, using
      minimally expensive, easily available materials.

PMID- 17560236
TI  - Bilaterally symmetric juvenile fibroadenomas and tubular breast deformity in a
      prepubescent girl.
AB  - Juvenile fibroadenomas are rare and usually not associated with other disease
      processes. We report the first known case of bilateral juvenile fibroadenomas in
      conjunction with tubular breast deformity in a prepubescent girl.

PMID- 17560237
TI  - Use of autogenous saphenous vein as a conduit for mesenterico-left portal vein
      bypass.
AB  - The authors describe a case of extrahepatic portal vein (EHPV) thrombosis and
      portal hypertension treated with a variant of mesenterico-left portal vein bypass
      (MLPVB) or Rex shunt. In this case, a segment of autogenous greater saphenous
      vein was used to bridge the distance between the left gastric vein inflow and the
      left portal vein. Use of such nontraditional conduit in similar circumstances may
      expand the application of portal revascularization/decompression procedures in
      treating these patients.

PMID- 17560238
TI  - Laparoscopic resection of a benign liver tumor in a child.
AB  - Laparoscopy for the resection of liver masses in children has remained
      undeveloped despite the wide acceptance of laparoscopy in the field of pediatric
      surgery. The authors report a case of nonanatomical laparoscopic hepatic
      resection of a large mesenchymal hamartoma in a 2-year-old boy. The procedure was
      performed using an innovative approach with a combination of different
      technologies that allowed for a safe and precise resection. This case
      demonstrates the feasibility of a nonanatomical laparoscopic hepatic resection,
      even for very large tumors. Both technical expertise and use of novel
      technologies are necessary to ensure a precise and controlled resection.

PMID- 17560239
TI  - Triad of tracheoesophageal fistula-esophageal atresia, pulmonary hypoplasia, and
      duodenal atresia.
AB  - We describe 3 cases of tracheoesophageal fistula with esophageal atresia who also
      had right pulmonary hypoplasia-aplasia and duodenal atresia. We review the
      current literature and propose that this may be a distinct association.

PMID- 17560240
TI  - Giant omental lipoblastoma in a 10-month-old infant composing 20% of total body
      weight.
AB  - Lipoblastoma of the greater omentum is an extremely rare benign tumor with less
      than 10 cases reported in the available literature. We report an unusual case of
      a 10-month-old girl with a giant omental lipoblastoma that composed 20% of her
      total body weight (1480 g, 17 x 12 x 16 cm). Complete excision of the tumor was
      performed. Histology confirmed the diagnosis of omental lipoblastoma.

PMID- 17560241
TI  - Very early manifestation of hereditary medullary thyroid cancer in carriers of
      intracellular-domain RET mutations.

PMID- 17560244
TI  - Although women comprised only 4% of all surgical consultants in the UK, the rate
      was 13% for pediatric surgery.

PMID- 17560245
TI  - ICAM-1 expression determines malignant potential of cancer.
AB  - HYPOTHESIS: Solid tumor cells bind to ICAM-1 on endothelial surfaces via MUC-1.
      Tumor binding to ICAM-1 auto-upregulates tumor ICAM-1 at the leading edge of the
      tumor and promotes release of chemoattractants for circulating macrophages, and
      circulating macrophages bind to tumor-expressed ICAM-1, invoking propagation of
      further chemokines and cytokines that recruit neutrophils. Tight adherence
      between cell surface ligands on neutrophils and tumor-expressed ICAM-1 activates
      neutrophils to degranulate, releasing elastases, which break down endovascular
      and endolymphatic barriers permitting transendothelial tumor cell migration.
      Consequently, tumor cell ICAM-1 expression dictates metastatic potential and
      metastatic potential determines cancer lethality.

PMID- 17560246
TI  - Comparison of data extraction from standardized versus traditional narrative
      operative reports for database-related research and quality control.
AB  - BACKGROUND: The purpose of this study was to compare the completeness and
      reproducibility of data extracted from a standardized operative report (SOR) with
      the non-standardized operative report (NSOR). METHODS: Between July and December
      2003, operative data were collected from all laparoscopic cholecystectomy
      procedures performed at the Peter Lougheed Centre Hospital. A standardized format
      for dictating laparoscopic cholecystectomy operative reports was introduced on
      October 1, 2003. Non-standardized operative reports dictated in the first 3
      months of the study period were compared with SORs dictated in the final 3
      months. Two physicians independently extracted data from each operative report
      into a surgical database. RESULTS: During the study period, 221 cholecystectomy
      reports were analyzed (119 SOR and 102 NSOR). Completeness of data extraction for
      identifying variables (eg, patient name, age, and date of procedure) was similar
      in the 2 types of reports. However, most other operative and perioperative
      details were more completely reported in the SOR (95% to 100%) when compared to
      the NSOR (14% to 100% complete). Furthermore, interobserver agreement between 2
      independent data extractors was better for the SOR than the NSOR (0.9972 vs
      0.9809, P < .0001). CONCLUSIONS: Standardized operative reports result in more
      complete and reliably interpretable operative data compared with NSORs.

PMID- 17560247
TI  - Impact of cardiac intraoperative precursor events on adverse outcomes.
AB  - BACKGROUND: Although extensive study has been directed at the influence of
      patient factors and comorbidities on cardiac surgical outcomes, less attention
      has been focused on process. We sought to examine the relationship between
      intraoperative precursor events (those events that precede and are requisite for
      the occurrence of an adverse event) and adverse outcomes themselves. METHODS:
      Anonymous, prospectively collected intraoperative data was merged with database
      outcomes for 450 patients undergoing major adult cardiac operations. Precursor
      events were categorized by type, person most affected, severity, and
      compensation. Number and categories of precursor events were analyzed as
      predictors of a composite outcome combining death or near miss complications
      (DNM), using logistic regression. RESULTS: Precursor events occurred more
      frequently in cases with a DNM outcome than in those with no adverse event (2.7
      +/- 2.4 vs 2.0 +/- 2.3/procedure, P = .005). After adjustment for other patient
      characteristics, the number of precursor events remained an independent predictor
      of DNM (RR, 1.14 per event [1.04 to 1.24]). Of 990 events, 35.6% related to
      management, 28.8% were technical, and 22.8% were environment-related. The surgeon
      was most affected in 40.8%, and 16.5% were of major severity. When categories of
      precursor events were analyzed, major severity events and those most affecting
      the surgeon were independent predictors of DNM. CONCLUSIONS: More detailed study
      of process in complex operations may lead to improved quality of care and patient
      safety. Special attention must be paid particularly to high risk patients and
      high risk precursor events.

PMID- 17560248
TI  - Is the laparoscopic adrenalectomy for pheochromocytoma the best treatment?
AB  - BACKGROUND: Laparoscopic adrenalectomy has become the gold standard for removing
      adrenal masses, but several authors still debate the role of laparoscopic
      adrenalectomy in pheochromocytoma. The purpose of this study was to evaluate the
      short- and long-term outcomes of laparoscopic versus open adrenalectomy for
      pheochromocytomas and to compare the feasibility and safety of laparoscopic
      adrenalectomy for neoplasms that are smaller than 6 cm versus those that are
      larger than 6 cm. METHODS: From January 1990 to December 2005, the same team in
      our department carried out 221 adrenalectomies in 211 patients. A total of 64 of
      these patients underwent 71 adrenalectomies for pheochromocytoma, 24 patients
      (37%) had open adrenalectomy, and 40 patients (63%) had laparoscopic
      adrenalectomy. Sex, age, side and size of lesion, operating time, duration of
      hospital stay, need for intensive care, intraoperative blood pressure variations,
      blood loss, postoperative analgesia, return to oral nutrition, and complications
      were compared among groups. RESULTS: An advantage of laparoscopic adrenalectomy
      over open adrenalectomy was observed in mean operating time, hospital stay, need
      for intensive care, intraoperative hypertension, intraoperative blood loss,
      postoperative analgesia, and return to oral nutrition (P <or= .035 in all). The
      analysis of tumor size (<or=6 vs >6 cm) in laparoscopic adrenalectomy showed that
      none of the variables differed significantly, except for intraoperative blood
      loss, which was greater for the larger neoplasms (P = .007). CONCLUSIONS:
      Laparoscopic adrenalectomy, when performed by experienced laparoscopic surgeons,
      is preferable to open adrenalectomy for the majority of pheochromocytomas, and as
      long as there is no evidence of invasion of surrounding structures, tumor size
      does not appear to have a profound effect on surgical outcome.

PMID- 17560249
TI  - Inguinal node dissection for melanoma in the era of sentinel lymph node biopsy.
AB  - BACKGROUND: With the introduction of sentinel lymph node (SLN) biopsy for
      melanoma, inguinal lymph node dissections (ILND) are more commonly performed for
      microscopic disease than for clinically palpable disease. We sought to examine
      the effect this change has on the morbidity of the operation. METHODS: A
      retrospective review was performed of all patients who underwent an ILND for
      melanoma between October 1997 and April, 2006. Clinical and pathologic data were
      collected and correlated by multivariate analysis with the incidence of a major
      wound complication. RESULTS: We identified 212 patients, 132 who underwent an
      ILND for a positive SLN and 80 for clinically palpable disease. Age, sex, and
      body mass index (BMI) were similar in both groups. Patients with clinically
      palpable disease had a significantly greater number of involved nodes (3.0 vs
      1.96, P = .0013), more often had >or=4 involved nodes (29% vs 9%, P < .001), and
      a greater incidence of extranodal extension (47% vs 5%, P < .001). Of the 212
      patients, 41 (19%) had a significant wound complication. This complication was
      significantly higher among patients with clinical disease compared to patients
      with a positive SLN (28% vs 14%, P = .02). Only BMI (odds ratio of 1.1) and the
      indication for the procedure (odds ratio of 2.2) were independent predictors of a
      major wound complication. Lymphedema occurred in 30% of the patients and was only
      significantly associated with clinical disease (41% vs 24%, P = .025). With a
      median follow-up of 2 years, regional recurrence was not significantly greater in
      patients with clinically palpable disease (13% vs 9%, P = not significant [ns]),
      although this result was possibly due to the significantly greater rate of
      distant recurrence (49% vs 18%, P < .001) and death (48% vs 21%) in these
      patients. CONCLUSIONS: Patients undergoing an ILND for a positive SLN have a
      significantly lower risk of postoperative complication or lymphedema than do
      patients undergoing ILND for clinically palpable disease. There is a benefit in
      regard to the morbidity of treatment in surgically staging melanoma patients by
      SLN biopsy and preventing ILND for palpable disease.

PMID- 17560250
TI  - Preoperative mapping of lymphatic drainage from the tumor using ferumoxide
      enhanced magnetic resonance imaging in clinical submucosal thoracic squamous cell
      esophageal cancer.
AB  - BACKGROUND: In thoracic esophageal cancer, lymph node metastases distribute
      widely from the neck to the abdominal area as a result of a complex
      periesophageal lymphatic network. The aim of the present study was to evaluate
      the potential clinical utility of a new method of mapping lymphatic drainage from
      tumors using ferumoxide-enhanced magnetic resonance imaging (MRI). METHODS:
      Twenty-three patients with clinical submucosal thoracic squamous cell esophageal
      cancer were examined. Ferumoxides were injected endoscopically into the
      peritumoral submucosal layer, after which their appearance in the lymph nodes in
      the neck, superior mediastinum, and abdomen was evaluated using MRI. RESULTS:
      Flux of ferumoxides from tumors was detected in all 23 patients. Among the 20
      patients with middle and lower thoracic esophageal cancers, there was no
      lymphatic drainage to the neck in 5 (25%) patients, none to the neck and superior
      mediastinum in 4 (20%), and none to the abdomen in 2 (10%), which could enable
      the extent of lymph node dissection to be reduced. We diagnosed clinical negative
      lymph node metastasis (N0) in 17 patients; the remaining 6 patients were
      diagnosed with clinical lymph node metastasis. Two patients (12%) diagnosed
      clinical N0, showed pathologic lymph node metastasis. Ferumoxide-enhanced MRI
      detected an influx of contrast agent into the metastatic node in both patients.
      CONCLUSIONS: Ferumoxide-enhanced MRI lymphatic mapping enables detection of the
      direction and area of lymphatic flux. It thus has the potential to improve our
      ability to gauge the appropriate extent of treatment in clinical submucosal
      squamous cell esophageal cancer.

PMID- 17560251
TI  - A modification of NIH consensus criteria to better distinguish the highly lethal
      subset of primary localized gastrointestinal stromal tumors: a subdivision of the
      original high-risk group on the basis of outcome.
AB  - BACKGROUND: By reappraising the National Institutes of Health (NIH) consensus
      criteria, we worked on establishing a modified scheme to identify highly lethal
      gastrointestinal stromal tumors (GISTs), which have an imperative demand for
      sequencing analysis to assess the suitability of an adjuvant imatinib trial.
      METHODS: Clinicopathologic features, including NIH and modified schemes, were
      retrospectively analyzed for 289 patients with localized GISTs. We combined the
      very low/low-risk GISTs into a single "risk level I" group (<or=5 cm, <5/50 high
      power fields [HPFs]) and redesignated the intermediate-risk GISTs as "risk level
      II" (either <5 cm, 6 to 10/50 HPFs or 5 to 10 cm, <5/50 HPFs). The GISTs of "risk
      level IV" group were >5 cm and >10/50 HPF, with the rest of high-risk GISTs
      defined as "risk level III." RESULTS: The cumulative 5-year rate of disease
      specific survival (DSS) for all 289 patients was 82%, and the DSS rates for
      patients with GISTs classified as risk levels I to IV were 100%, 96%, 67%, and
      25% at 5 years, respectively. The prognostic differences were striking between
      the risk level II and III groups (P < .0001) and between the risk level III and
      IV groups (P = .0002). The higher risk level of our scheme represented the
      strongest independent adverse factor (risk ratio [RR] = 11.299 for risk level
      III; RR = 33.815 for risk level IV; P < .0001), followed by mixed/epithelioid
      histology (RR = 2.837, P = .003) and older age (>or=70 years, RR = 1.955, P =
      .044). CONCLUSIONS: Remarkable prognostic heterogeneity exists in the high-risk
      category of the NIH scheme, which is not as effective as the modified criteria in
      identifying highly lethal GISTs that we classified as risk level IV.

PMID- 17560252
TI  - Subclassification of pT2 gastric adenocarcinoma according to depth of invasion
      (pT2a vs pT2b) and lymph node status (pN).
AB  - BACKGROUND: We investigated prognostic differences according to nodal status in
      patients with pT2a and pT2b stage gastric cancers. METHODS: The clinicopathologic
      outcomes of 1118 patients who underwent curative resection and had 15 or more
      lymph nodes evaluated for pT2 stage gastric cancers between 1986 and 1996 were
      reviewed retrospectively. Of the study group, 442 (39.5%) patients had pT2a stage
      gastric cancers and 676 (60.5%) had pT2b stage gastric cancers. RESULTS: The
      rates of lymph node metastasis for the pTa and pT2b groups were 53.8% and 71.0%,
      respectively (P < .001). The disease-specific 5-year survival rate of patients
      with pT2a cancers was significantly longer than for those with pT2b cancers
      (85.5% vs 55.7%, P < .001). The prognosis of patients with pT2a gastric cancers
      was significantly better than that of patients with pT2b cancers on any pN stage
      (P < .001). Multivariate analysis identified age, pT, and pN stages as
      independent prognostic factors for patients with pT2 gastric cancers. Patients
      with pT2aN0 (stage IB) cancers showed the best survival. Patents with pT2aN1
      (stage II) and pT2bN0 (stage IB) cancers had similar survival rates, as did
      patients with pT2aN2 (stage IIIA) and pT2bN1 (stage II) cancers. CONCLUSIONS: The
      subclassification of pT2 gastric cancers into pT2a or pT2b is necessary to
      demonstrate their different prognoses. We propose that the current stage grouping
      should be modified to better represent the prognosis for patients with stage pT2
      gastric cancers.

PMID- 17560253
TI  - Flow patterns and preferred sites of intimal thickening in diameter-mismatched
      vein graft interpositions.
AB  - BACKGROUND: It is suspected that blood flow and flow-induced shear stress play an
      important role in the pathogenesis and localization of intimal hyperplasia in
      anastomosed vessels. However, experimental data that demonstrate the correlation
      between the flow and the sites of intimal thickening obtained in the same vessel
      are scarce. For this reason, we have studied the relationship between the flow
      and precise locations of wall thickening specific to the particular vessel by
      performing diameter-mismatched vein graft interpositions. This method created
      more flow disturbances than those found in our previous study, which was carried
      out by dividing an artery and simply suturing its ends back to their original
      positions. METHODS: In the current study, grafting procedures consisting of 26
      saphenous vein interpositions and 10 jugular vein interpositions were carried out
      on the femoral arteries of 22 adult mongrel dogs. The vessels were harvested at 3
      months after operation, perfusion-fixed, and rendered transparent. The precise
      location and the size of intimal thickening and characteristics of the flow, such
      as flow patterns, distributions of fluid velocity, and wall shear stress, were
      studied in detail by means of flow visualization and cinemicrographic techniques.
      RESULTS: It was found that the diameters of interposed saphenous vein grafts,
      which were about one-half the diameter of host arteries, increased drastically
      and became almost the same as those of the host arteries. Intimal thickening was
      found distal to the distal anastomotic junction in smaller diameter saphenous
      vein-interposed vessels and distal to the proximal anastomotic junction in larger
      diameter jugular vein-interposed vessels. In both cases, flow was disturbed with
      the formation of a slow recirculation flow due to a sudden enlargement of vessel
      diameter caused by a mismatch of vessel diameters at the anastomotic junction and
      at the location where the wall shear stress was low. CONCLUSIONS: The results
      suggest that the key hemodynamic factors involved in the localization of intimal
      thickening are the low velocity of flowing blood and the resultant low shear
      stress acting on the vessel wall.

PMID- 17560254
TI  - Oral vitamin D supplementation reduces the incidence of eucalcemic PTH elevation
      after surgery for primary hyperparathyroidism.
AB  - BACKGROUND: As many as 43% of patients will have normocalcemic intact parathyroid
      hormone (PTH) elevation after undergoing curative parathyroidectomy for primary
      hyperparathyroidism. This phenomenon may be due in part to an absolute or
      relative deficiency of vitamin D, which is under-recognized in patients with
      primary hyperparathyroidism. METHODS: From September 1, 2004, to September 30,
      2005, 86 consecutive patients underwent parathyroidectomy for primary sporadic
      hyperparathyroidism (psHPT). The patients were segregated into 2 groups based on
      postoperative management. Group 1 was composed of 26 patients who received
      routine oral calcitriol and calcium carbonate postoperatively. The 60 patients in
      the second group (group 2) received calcium carbonate postoperatively at the
      discretion of the primary surgeon. RESULTS: A total of 85 patients (99%) achieved
      postoperative cure with sustained reduction in serum calcium. Within 30 days
      postoperatively, mean serum PTH levels normalized in both groups (41 +/- 31 vs 39
      +/- 31 pg/ml; P = .91). However, at 1 to 3 months postoperatively, mean serum
      calcium levels remained similar (9.5 +/- 0.7 vs 9.3 +/- 0.5 mg/dl; P = .39)
      whereas mean serum PTH levels in groups 1 and 2 were 43 +/- 25 pg/ml and 67 +/-
      45 pg/ml (P = .02), respectively. At 4 to 6 months postoperatively, mean PTH was
      again higher in group 2 (36 +/- 22 vs 67 +/- 35; P = .03), whereas mean serum
      calcium levels were normal (9.2 +/- 0.8 vs 9.6 +/- 0.4 mg/dl; P = .18). The
      incidence of postoperative normocalcemic PTH elevation was significantly higher
      in group 2 at 1 to 3 months (14% vs 39%; P = .04) and at 7 to 12 months (22% vs
      83%; P = .04). CONCLUSIONS: Vitamin D supplementation following parathyroidectomy
      for primary hyperparathyroidism reduces the incidence of postoperative eucalcemic
      PTH elevation.

PMID- 17560255
TI  - Histone deacetylase as therapeutic target in a rodent model of hemorrhagic shock:
      effect of different resuscitation strategies on lung and liver.
AB  - BACKGROUND: DNA transcription is regulated in part by acetylation of nuclear
      histones, controlled by 2 groups of enzymes: histone deacetylases (HDAC) and
      histone acetyl transferases (HAT). We have shown previously that hemorrhage and
      resuscitation are associated with HDAC/HAT imbalance, which influences the
      acetylation status of cardiac histones. The goals of this study were to determine
      whether: (1) resuscitation after hemorrhage affects histone acetylation in a
      fluid- and organ-specific fashion; and (2) administration of HDAC inhibitors
      influences histone acetylation and subsequent gene expression. METHODS: In the
      first experiment, rats (n = 6/group) were subjected to volume-controlled
      hemorrhage and resuscitated with: (1) racemic lactated Ringer's (DL-LR); (2) L
      lactated Ringer's (L-LR); (3) 7.5% hypertonic saline (HTS); (4) ketone Ringer's
      (KR); or (5) pyruvate Ringer's (PR). Control groups included: (6) no hemorrhage
      (Sham); and (7) hemorrhage with no resuscitation (NR). In the second experiment
      (n = 5/group), 3 HDAC inhibitors, valproic acid (VPA), trichostatin A (TSA), and
      suberoylanilide hydroxamic acid (SAHA), were added to normal saline and used as
      fluid for resuscitation. At the end of resuscitation, lung and liver tissues were
      subjected to subcellular protein fractionation and Western blotting to analyze
      histone acetylation. In addition, cDNA microarrays and RT-PCR were used to
      measure expression of selected genes. RESULTS: Hemorrhage did not change the
      level of histone acetylation in lungs, whereas resuscitation predominantly
      hyperacetylated histones. An analysis of histone acetylation on 10 lysine sites
      showed that L-LR, HTS, and KR resuscitation caused the largest number of changes
      (7, 6, and 6 respectively). SAHA hyperacetylated 7 sites in liver and affected
      expression of 57 genes (44 up, 13 down). CONCLUSIONS: Resuscitation with various
      fluids, as well as infusion of pharmacologic HDAC inhibitors affects histone
      acetylation in a fluid- and organ-specific fashion, even when administered post
      insult for a limited period of time. Uniquely affected genes are associated with
      metabolism, cellular growth, proliferation, differentiation, transformation, and
      cellular signaling.

PMID- 17560256
TI  - Relationship between energetic stress and pro-apoptotic/cytoprotective kinase
      mechanisms in intestinal preservation.
AB  - BACKGROUND: A recent study from our laboratory documented significant
      improvements in post-transplant viability in an experimental model of intestinal
      transplantation when a novel, nutrient-rich preservation solution was used during
      cold storage. The current study investigated the relationship between
      energetic/oxidative stress responses and fundamental kinase signaling events
      during the period of organ storage. This relationship may be a key factor
      contributing to improved graft viability after storage in a nutrient-rich
      preservation solution. METHODS: Rat small intestine was harvested and flushed
      intraluminally with University of Wisconsin (UW) solution or an amino acid-rich
      (AA) solution as follows: Group 1, no luminal flush (clinical control); Group 2,
      luminal UW solution; Group 3, luminal AA solution. Energetics (ATP, total
      adenylates), oxidative stress (malondialdehyde), histology, and MAPK (P38, JNK,
      ERK)/AMPK/Caspase-3 were assessed throughout 12-hour cold storage. RESULTS: P38
      and JNK were upregulated strongly in Group 2 after 1- and 12-hour storage. Group
      3 exhibited a delayed activation and subsequent downregulation of these pre
      apoptotic signals. Between 6 to 12 hours, a strong upregulation of ERK was
      observed in Group 3. AMPK downregulation correlated with a reduction in AMP/ATP
      ratio, ERK upregulation, and P38/JNK downregulation in Group 3. After 12-hour
      storage, histology indicated superior preservation of mucosal architecture in
      Group 3 tissues. CONCLUSIONS: A nutrient-rich preservation solution abrogates pre
      apoptotic signaling (JNK and P38) and upregulates cytoprotective signals (ERK).
      Our data support the concept of a concerted effort facilitating cellular
      protection in response to ischemic stress.

PMID- 17560257
TI  - Integrin-mediated laminin-1 adhesion upregulates CXCR4 and IL-8 expression in
      pancreatic cancer cells.
AB  - BACKGROUND: We have shown recently that alpha(2)beta(1) integrin-mediated type I
      collagen adhesion promotes a more malignant phenotype in pancreatic cancer cell
      lines than other extracellular matrix (ECM) proteins. MiaPaCa-2 cells, by
      contrast, do not express collagen-binding integrins, but are metastatic in our
      orthotopic mouse model and migrate maximally on laminin-1 (Ln-1). It has also
      been shown that CXCR4 and IL-8 expression correlates directly with metastasis in
      pancreatic cancer in vivo. We therefore examined the potential of the ECM to
      regulate CXCR4 and IL-8 expression in pancreatic cancer cells. METHODS: We
      cultured 8 pancreatic cancer cell lines on fibronectin (Fn), types I and IV
      collagen, Ln-1 and vitronectin (Vn), and examined cell lysates for CXCR4 by
      immunoblotting and media for IL-8 by ELISA. We also conducted cell migration
      assays with stromal-derived factor-1 (SDF-1) as the chemoattractant to examine
      integrin-binding specificity and CXCR4 function. RESULTS: All cell lines
      expressed CXCR4 protein. MiaPaCa-2 cell growth on Ln-1 increased significantly
      CXCR4 and IL-8 expression relative to other ECM proteins. Migration inhibition
      studies showed that both the alpha(6)beta(1) and alpha(3)beta(1) integrins
      mediate MiaPaCa-2 migration on Ln-1. Growth studies showed further that CXCR4
      expression on Ln-1 was mediated by the alpha(6)beta(1) integrin whereas IL-8
      expression was mediated by both the alpha(6)beta(1) and alpha(3)beta(1)
      integrins. The expression of functional CXCR4 was also shown in migration assays,
      where SDF-1 significantly increased pancreatic cancer cell chemotaxis on Ln-1.
      CONCLUSIONS: These data indicate that integrin-mediated Ln-1 adhesion upregulates
      CXCR4 and IL-8 expression and may play a mechanistic role in pancreatic cancer
      metastases.

PMID- 17560258
TI  - Hyaluronic acid is a useful tool for intraoperative sentinel node detection in
      gastric cancer surgery.
AB  - BACKGROUND: We assessed whether a mixture of hyaluronic acid (HA) and dye can
      facilitate dye-guided sentinel node (SN) mapping in gastric surgery. Although dye
      guided, SN-navigated surgery is clinically applied for the treatment of early
      gastric cancer, there are still some practical problems. Because dyes are carried
      out from the SN within 20 to 30 minutes, it is sometimes difficult to detect SNs
      accurately, especially when they are located in a deep area in obese patients.
      METHODS: Patent blue or ferumoxides, superparamagnetic iron nanocolloids, with or
      without HA, were injected into the gastrointestinal tract of the pig, and the
      time course of dye transfer through the lymphatic system of the pig mesentery was
      assessed. RESULTS: When a mixture of HA and patent blue at a volume ratio of 1:4
      was injected into the submucosal layer, the time to stain the SN did not differ
      from that with patent blue alone; however, HA markedly prolonged the time the
      blue dye was retained in the SN. Patent blue alone stained the efferent
      lymphatics of the SN and spread to other lymph nodes within 20 minutes after
      submucosal injection. At the same time point, in contrast, blue stain was
      restricted to a part of the SN, and the efferent lymphatics were not stained for
      2 hours when patent blue was mixed with HA. When a mixture of HA and ferumoxides
      was used as the tracer, the ferumoxides were still observed in the mesenteric SN
      even at 2 days after injection. Iron staining showed that Fe was trapped
      primarily in cells in the peripheral sinus of the SN, suggesting that the iron
      nanoparticles were mostly incorporated by phagocytic macrophages in the SN within
      a few hours. CONCLUSIONS: Our data indicate that a mixture with HA prolongs the
      stay of a dye tracer in the SN and thus enables easy and accurate detection of
      the SN. HA may be a useful tool to develop a more sophisticated SN mapping
      technique.

PMID- 17560259
TI  - Primary angiosarcoma of the breast.

PMID- 17560260
TI  - Colonic duplication associated with anterior spinal bar and left-sided inferior
      vena cava.

PMID- 17560261
TI  - NPO after midnight.

PMID- 17560262
TI  - Analysis of efficacy and safety of drotrecogin alfa (activated) in surgical
      patients, using an international integrated database.

PMID- 17560263
TI  - A modified triangular venoplasty for reconstruction of middle hepatic vein
      tributaries in living donor liver transplantation.

PMID- 17560264
TI  - Recognizing genes regulated by the MEN1 gene, using RNAi and microarrays:
      Evidence-based rebuttal.

PMID- 17560265
TI  - Recanalized umbilical vein as a conduit for anterior sector venous outflow
      reconstruction in right lobe grafts.

PMID- 17560266
TI  - Re: "Psychomotor testing predicts rate of skill acquisition for proficiency-based
      laparoscopic skills training".

PMID- 17560267
TI  - Middle hepatic vein reconstruction of right liver graft using the glutaraldehyde
      treated acellular bovine pericardium.

PMID- 17560268
TI  - Re: "Intraductal papillary-mucinous neoplasms and mucinous cystic neoplasms of
      the pancreas differentiated by ovarian-type stroma".

PMID- 17560270
TI  - Discovery of activation-induced cytidine deaminase, the engraver of antibody
      memory.
AB  - Discovery of activation-induced cytidine deaminase (AID) paved a new path to
      unite two genetic alterations induced by antigen stimulation; class switch
      recombination (CSR) and somatic hypermutation (SHM). AID is now established to
      cleave specific target DNA and to serve as engraver of these genetic alterations.
      AID of a 198-residue protein has four important domains: nuclear localization
      signal and SHM-specific region at the N-terminus; the alpha-helical segment
      (residue 47-54) responsible for dimerization; catalytic domain (residues 56-94)
      shared by all the other cytidine deaminase family members; and nuclear export
      signal overlapping with class switch-specific domain at the C-terminus. Two
      alternative models have been proposed for the mode of AID action; whether AID
      directly attacks DNA or indirectly through RNA editing. Lines of evidence
      supporting RNA editing hypothesis include homology in various aspects with
      APOBEC1, a bona fide RNA editing enzyme as well as requirement of de novo protein
      synthesis for DNA cleavage by AID in CSR and SHM. This chapter critically
      evaluates DNA deamination hypothesis and describes evidence to indicate UNG is
      involved not in DNA cleavage but in DNA repair of CSR. In addition, UNG appears
      to have a noncanonical function through interaction with an HIV Vpr-like protein
      at the WXXF motif. Taken together, RNA editing hypothesis is gaining the ground.

PMID- 17560271
TI  - DNA deamination in immunity: AID in the context of its APOBEC relatives.
AB  - The activation-induced cytidine deaminase (AID)/apolipoprotein B RNA-editing
      catalytic component (APOBEC) family is a vertebrate-restricted subgrouping of a
      superfamily of zinc (Zn)-dependent deaminases that has members distributed
      throughout the biological world. AID and APOBEC2 are the oldest family members
      with APOBEC1 and the APOBEC3s being later arrivals restricted to placental
      mammals. Many AID/APOBEC family members exhibit cytidine deaminase activity on
      polynucleotides, although in different physiological contexts. Here, we examine
      the AID/APOBEC proteins in the context of the entire Zn-dependent deaminase
      superfamily. On the basis of secondary structure predictions, we propose that the
      cytosine and tRNA deaminases are likely to provide better structural paradigms
      for the AID/APOBEC family than do the cytidine deaminases, to which they have
      conventionally been compared. These comparisons yield predictions concerning
      likely polynucleotide-interacting residues in AID/APOBEC3s, predictions that are
      supported by mutagenesis studies. We also focus on a specific comparison between
      AID and the APOBEC3s. Both are DNA deaminases that function in immunity and are
      responsible for the hypermutation of their target substrates. AID functions in
      the adaptive immune system to diversify antibodies with targeted DNA deamination
      being central to this function. APOBEC3s function as part of an innate pathway of
      immunity to retroviruses with targeted DNA deamination being central to their
      activity in retroviral hypermutation. However, the mechanism by which the
      APOBEC3s fulfill their function of retroviral restriction remains unresolved.

PMID- 17560272
TI  - The role of activation-induced deaminase in antibody diversification and
      chromosome translocations.
AB  - Although B and T lymphocytes are similar in many respects including
      diversification of their antigen receptor genes by V(D)J recombination, 95% of
      all lymphomas diagnosed in the western world are of B-cell origin. Many of these
      are derived from mature B cells [Kuppers, R. (2005). Mechanisms of B-cell
      lymphoma pathogenesis. Nat. Rev. Cancer 5, 251-262] and display hallmark
      chromosome translocations involving immunoglobulin genes and a proto-oncogene
      partner whose expression becomes deregulated as a result of the translocation
      reaction [Kuppers, R. (2005). Mechanisms of B-cell lymphoma pathogenesis. Nat.
      Rev. Cancer 5, 251-262; Kuppers, R., and Dalla-Favera, R. (2001). Mechanisms of
      chromosomal translocations in B cell lymphomas. Oncogene 20, 5580-5594]. These
      translocations are essential to the etiology of B-cell neoplasms. Here we will
      review how the B-cell specific molecular events required for immunoglobulin class
      switch recombination are initiated and how they contribute to chromosome
      translocations in vivo.

PMID- 17560273
TI  - Targeting of AID-mediated sequence diversification by cis-acting determinants.
AB  - After their assembly by V(D)J recombination, immunoglobulin (Ig) genes undergo
      somatic hypermutation, gene conversion, and class switch recombination to
      generate additional antibody diversity. The three diversification processes
      depend on activation-induced cytidine deaminase (AID) and are tightly linked to
      transcription. The reactions occur primarily on Ig genes and the molecular
      mechanisms that underlie their targeting to Ig loci have been of intense
      interest. In this chapter, we discuss the evidence linking transcription and
      transcriptional control elements to the three diversification pathways, and we
      consider how various features of chromatin could render parts of the genome
      permissive for AID-mediated sequence diversification.

PMID- 17560274
TI  - AID-initiated purposeful mutations in immunoglobulin genes.
AB  - Exposure brings risk to all living organisms. Using a remarkably effective
      strategy, higher vertebrates mitigate risk by mounting a complex and
      sophisticated immune response to counter the potentially toxic invasion by a
      virtually limitless army of chemical and biological antagonists. Mutations are
      almost always deleterious, but in the case of antibody diversification there are
      mutations occurring at hugely elevated rates within the variable (V) and switch
      regions (SR) of the immunoglobulin (Ig) genes that are responsible for binding to
      and neutralizing foreign antigens throughout the body. These mutations are truly
      purposeful. This chapter is centered on activation-induced cytidine deaminase
      (AID). AID is required for initiating somatic hypermutation (SHM) in the V
      regions and class switch recombination (CSR) in the SR portions of Ig genes. By
      converting C --> U, while transcription takes place, AID instigates a cascade of
      mutational events involving error-prone DNA polymerases, base excision and
      mismatch repair enzymes, and recombination pathways. Together, these processes
      culminate in highly mutated antibody genes and the B cells expressing antibodies
      that have achieved optimal antigenic binding undergo positive selection in
      germinal centers. We will discuss the biological role of AID in this complex
      process, primarily in terms of its biochemical properties in relation to SHM in
      vivo. The chapter also discusses recent advances in experimental methods to
      characterize antibody dynamics as a function of SHM to help elucidate the role
      that the AID-induced mutations play in tailoring molecular recognition. The
      emerging experimental techniques help to address long-standing conundrums
      concerning evolution-imposed constraints on antibody structure and function.

PMID- 17560275
TI  - Evolution of the immunoglobulin heavy chain class switch recombination mechanism.
AB  - To mount an optimum immune response, mature B lymphocytes can change the class of
      expressed antibody from IgM to IgG, IgA, or IgE through a recombination/deletion
      process termed immunoglobulin heavy chain (IgH) class switch recombination (CSR).
      CSR requires the activation-induced cytidine deaminase (AID), which has been
      shown to employ single-stranded DNA as a substrate in vitro. IgH CSR occurs
      within and requires large, repetitive sequences, termed S regions, which are
      parts of germ line transcription units (termed "C(H) genes") that are composed of
      promoters, S regions, and individual IgH constant region exons. CSR requires and
      is directed by germ line transcription of participating C(H) genes prior to CSR.
      AID deamination of cytidines in S regions appears to lead to S region double
      stranded breaks (DSBs) required to initiate CSR. Joining of two broken S regions
      to complete CSR exploits the activities of general DNA DSB repair mechanisms. In
      this chapter, we discuss our current knowledge of the function of S regions, germ
      line transcription, AID, and DNA repair in CSR. We present a model for CSR in
      which transcription through S regions provides DNA substrates on which AID can
      generate DSB-inducing lesions. We also discuss how phosphorylation of AID may
      mediate interactions with cofactors that facilitate access to transcribed S
      regions during CSR and transcribed variable regions during the related process of
      somatic hypermutation (SHM). Finally, in the context of this CSR model, we
      further discuss current findings that suggest synapsis and joining of S region
      DSBs during CSR have evolved to exploit general mechanisms that function to join
      widely separated chromosomal DSBs.

PMID- 17560276
TI  - Beyond SHM and CSR: AID and related cytidine deaminases in the host response to
      viral infection.
AB  - As the primary effector of immunoglobulin somatic hypermutation (SHM) and class
      switch recombination (CSR), activation-induced cytidine deaminase (AID) serves an
      important function in the adaptive immune response. Recent advances have
      demonstrated that AID and a group of closely related cytidine deaminases, the
      APOBEC3 proteins, also act in the innate host response to viral infection.
      Antiviral activity was first attributed to APOBEC3G as a potent inhibitor of HIV.
      It is now apparent that the targets of the APOBEC3 proteins extend beyond HIV,
      with family members acting against a wide variety of viruses as well as host
      encoded retrotransposable genetic elements. Although it appears to function
      through a different mechanism, AID also possesses antiviral properties.
      Independent of its antibody diversification functions, AID protects against
      transformation by Abelson murine leukemia virus (Ab-MLV), an oncogenic
      retrovirus. Additionally, AID has been implicated in the host response to other
      pathogenic viruses. These emerging roles for the AID/APOBEC cytidine deaminases
      in viral infection suggest an intriguing evolutionary connection of innate and
      adaptive immune mechanisms.

PMID- 17560277
TI  - Role of AID in tumorigenesis.
AB  - A hallmark of mature B-cell lymphomas is reciprocal chromosomal translocations
      involving the Ig locus and a proto-oncogene, which usually result in the
      deregulated, constitutive expression of the translocated gene. In addition to
      such translocations, proto-oncogenes are frequently hypermutated in germinal
      center (GC)-derived B-cell lymphomas. Although aberrant, mistargeted class switch
      recombination (CSR) and somatic hypermutation (SHM) events have long been
      suspected of causing chromosomal translocations and mutations in oncogenes, and
      thus of playing a critical role in the pathogenesis of most B-cell lymphomas, the
      molecular basis for such deregulation of CSR and SHM is only beginning to be
      elucidated by recent genetic approaches. The tumorigenic ability of activation
      induced cytidine deaminase (AID), a key enzyme that initiates CSR and SHM, was
      revealed in studies on AID transgenic mice. In addition, experiments with AID
      deficient mice clearly showed that AID is required not only for the c-myc/IgH
      translocation but also for the malignant progression of translocation-bearing
      lymphoma precursor cells, probably by introducing additional genetic hits.
      Normally, AID expression is only transiently and specifically induced in
      activated B cells in GCs. However, recent studies indicate that AID can be
      induced directly in B cells outside the GCs by various pathogens, including
      transforming viruses associated with human malignancies. Indeed, AID expression
      is not restricted to GC-derived B-cell lymphomas, but is also found in other
      types of B-cell lymphoma and even in nonlymphoid tumors, suggesting that
      ectopically expressed AID is involved in tumorigenesis and disease progression in
      a wide variety of cell types.

PMID- 17560278
TI  - Pathophysiology of B-cell intrinsic immunoglobulin class switch recombination
      deficiencies.
AB  - B-cell intrinsic immunoglobulin class switch recombination (Ig-CSR) deficiencies,
      previously termed hyper-IgM syndromes, are genetically determined conditions
      characterized by normal or elevated serum IgM levels and an absence or very low
      levels of IgG, IgA, and IgE. As a function of the molecular mechanism, the
      defective CSR is variably associated to a defect in the generation of somatic
      hypermutations (SHMs) in the Ig variable region. The study of Ig-CSR deficiencies
      contributed to a better delineation of the mechanisms underlying CSR and SHM, the
      major events of antigen-triggered antibody maturation. Four Ig-CSR deficiency
      phenotypes have been so far reported: the description of the activation-induced
      cytidine deaminase (AID) deficiency (Ig-CSR deficiency 1), caused by recessive
      mutations of AICDA gene, characterized by a defect in CSR and SHM, clearly
      established the role of AID in the induction of the Ig gene rearrangements
      underlying CSR and SHM. A CSR-specific function of AID has, however, been
      detected by the observation of a selective CSR defect caused by mutations
      affecting the C-terminus of AID. Ig-CSR deficiency 2 is the consequence of uracil
      N-glycosylase (UNG) deficiency. Because UNG, a molecule of the base excision
      repair machinery, removes uracils from DNA and AID deaminates cytosines into
      uracils, that observation indicates that the AID-UNG pathway directly targets DNA
      of switch regions from the Ig heavy-chain locus to induce the CSR process. Ig-CSR
      deficiencies 3 and 4 are characterized by a selective CSR defect resulting from
      blocks at distinct steps of CSR. A further understanding of the CSR machinery is
      expected from their molecular definition.

PMID- 17560279
TI  - LEM-Domain proteins: new insights into lamin-interacting proteins.
AB  - LEM-domain proteins present a growing family of nonrelated inner nuclear membrane
      and intranuclear proteins, including emerin, MAN1, LEM2, several alternatively
      spliced isoforms of LAP2, and various uncharacterized proteins in higher
      eukaryotes as well as the Drosophila-specific proteins otefin and Bocksbeutel.
      LEM-domain proteins are involved in diverse cellular processes including
      replication and cell cycle control, chromatin organization and nuclear assembly,
      the regulation of gene expression and signaling pathways, as well as retroviral
      infection. Genetic analyses in different model organisms reveal new insights into
      the various functions of LEM-domain proteins, lamins, and their involvement in
      laminopathic diseases. All these findings as well as previously proposed ideas
      and models have been summarized to broaden our view of this exciting protein
      family.

PMID- 17560280
TI  - New insights into membrane trafficking and protein sorting.
AB  - Protein transport in the secretory and endocytic pathways is a multistep process
      involving the generation of transport carriers loaded with defined sets of cargo,
      the shipment of the cargo-loaded transport carriers between compartments, and the
      specific fusion of these transport carriers with a target membrane. The
      regulation of these membrane-mediated processes involves a complex array of
      protein and lipid interactions. As the machinery and regulatory processes of
      membrane trafficking have been defined, it is increasingly apparent that membrane
      transport is intimately connected with a number of other cellular processes, such
      as quality control in the endoplasmic reticulum (ER), cytoskeletal dynamics,
      receptor signaling, and mitosis. The fidelity of membrane trafficking relies on
      the correct assembly of components on organelles. Recruitment of peripheral
      proteins plays a critical role in defining organelle identity and the
      establishment of membrane subdomains, essential for the regulation of vesicle
      transport. The molecular mechanisms for the biogenesis of membrane subdomains are
      also central to understanding how cargo is sorted and segregated and how
      different populations of transport carriers are generated. In this review we will
      focus on the emerging themes of organelle identity, membrane subdomains,
      regulation of Golgi trafficking, and advances in dissecting pathways in
      physiological systems.

PMID- 17560281
TI  - Structure and function of the atypical orphan nuclear receptor small heterodimer
      partner.
AB  - The small heterodimer partner (SHP; NROB2) is a member of the nuclear receptor
      superfamily and is classified as an "orphan" subgroup, as its ligand has not yet
      been identified. SHP lacks the classical DNA-binding domain found in most nuclear
      receptors and functions as a transcriptional coregulator by directly interacting
      with nuclear receptors and other transcription factors. SHP regulates the
      transcription of a variety of target genes and controls a variety of
      physiological functions. For the past 10 years, great progress has been made in
      our understanding of the mechanism of action of SHP and the regulation of SHP
      gene expression. Many of the results imply that SHP has a variety of roles in the
      regulation of metabolic homeostasis. In this review, we discuss the current state
      of understanding of the structure, expression, and function of the orphan nuclear
      receptor, SHP.

PMID- 17560282
TI  - Zebrafish gastrulation: cell movements, signals, and mechanisms.
AB  - Gastrulation is a morphogenetic process that results in the formation of the
      embryonic germ layers. Here we detail the major cell movements that occur during
      zebrafish gastrulation: epiboly, internalization, and convergent extension.
      Although gastrulation is known to be regulated by signaling pathways such as the
      Wnt/planar cell polarity pathway, many questions remain about the underlying
      molecular and cellular mechanisms. Key factors that may play a role in
      gastrulation cell movements are cell adhesion and cytoskeletal rearrangement. In
      addition, some of the driving force for gastrulation may derive from tissue
      interactions such as those described between the enveloping layer and the yolk
      syncytial layer. Future exploration of gastrulation mechanisms relies on the
      development of sensitive and quantitative techniques to characterize embryonic
      germ-layer properties.

PMID- 17560283
TI  - Calcium dynamics: spatio-temporal organization from the subcellular to the organ
      level.
AB  - Many essential physiological processes are controlled by calcium. To ensure
      reliability and specificity, calcium signals are highly organized in time and
      space in the form of oscillations and waves. Interesting findings have been
      obtained at various scales, ranging from the stochastic opening of a single
      calcium channel to the intercellular calcium wave spreading through an entire
      organ. A detailed understanding of calcium dynamics thus requires a link between
      observations at different scales. It appears that some regulations such as
      calcium-induced calcium release or PLC activation by calcium, as well as the weak
      diffusibility of calcium ions play a role at all levels of organization in most
      cell types. To comprehend how calcium waves spread from one cell to another,
      specific gap-junctional coupling and paracrine signaling must also be taken into
      account. On the basis of a pluridisciplinar approach ranging from physics to
      physiology, a unified description of calcium dynamics is emerging, which could
      help understanding how such a small ion can mediate so many vital functions in
      living systems.

PMID- 17560284
TI  - New technologies used in the study of human melanoma.
AB  - The amount of information on tumor biology has expanded enormously, essentially
      due to the completion of the human genome sequencing and to the application of
      new technologies that represent an exciting breakthrough in molecular analysis.
      Often these data spring from experimental procedures, such as a serial analysis
      of gene expression (SAGE) and DNA microarrays, which cannot be defined as
      hypothesis-driven: it may appear to be a "brute force" approach through which no
      information can be directly generated concerning the specific functions of
      selected genes in a definite context. However, interesting results are fruitfully
      generated, and thus it is important to consider the enormous potential these new
      technologies possess and to learn how to apply this novel form of knowledge in
      the emerging field of molecular medicine. This review, after a limited outline
      regarding several classic aspects of human cutaneous melanoma biology, genetics,
      and clinical approaches, will focus on the proficient use of up-to-date
      technologies in the study of the neoplastic disease and on their capability to
      provide effective support to conventional approaches in melanoma diagnosis,
      prognosis, and treatment.

PMID- 17560285
TI  - PTK787/ZK 222584, a small molecule tyrosine kinase receptor inhibitor of vascular
      endothelial growth factor (VEGF), has modest activity in myelofibrosis with
      myeloid metaplasia.
AB  - Angiogenesis is part of the pathophysiology of myelofibrosis with myeloid
      metaplasia (MMM). PTK787/ZK 222584 (PTK/ZK) is a novel inhibitor of vascular
      endothelial growth factor receptors. Twenty-nine patients with MMM received a
      continuous dosing schedule of PTK/ZK doses of 500 or 750 mg twice daily (BID).
      Transient potentially PTK/ZK related mild nausea, vomiting, dizziness, fatigue,
      thrombocytopenia, or anorexia occurred in 15% of patients. Dose limiting
      toxicities of dyspepsia, proteinurea, and/or mucositis were observed in patients
      treated with 750 mg BID. One (3%) and five (17%) patients achieved complete
      remission and clinical improvement, respectively. PTK/ZK has modest activity in
      patients with MMM.

PMID- 17560286
TI  - The role of coenzyme Q10 in statin-associated myopathy: a systematic review.
AB  - Statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) are
      currently the most effective medications for reducing low-density lipoprotein
      cholesterol concentrations. Although generally safe, they have been associated
      with a variety of myopathic complaints. Statins block production of farnesyl
      pyrophosphate, an intermediate in the synthesis of ubiquinone or coenzyme Q10
      (CoQ10). This fact, plus the role of CoQ10 in mitochondrial energy production,
      has prompted the hypothesis that statin-induced CoQ10 deficiency is involved in
      the pathogenesis of statin myopathy. We identified English language articles
      relating statin treatment and CoQ10 levels via a PubMed search through August
      2006. Abstracts were reviewed and articles addressing the relationship between
      statin treatment and CoQ10 levels were examined in detail. Statin treatment
      reduces circulating levels of CoQ10. The effect of statin therapy on
      intramuscular levels of CoQ10 is not clear, and data on intramuscular CoQ10
      levels in symptomatic patients with statin-associated myopathy are scarce.
      Mitochondrial function may be impaired by statin therapy, and this effect may be
      exacerbated by exercise. Supplementation can raise the circulating levels of
      CoQ10, but data on the effect of CoQ10 supplementation on myopathic symptoms are
      scarce and contradictory. We conclude that there is insufficient evidence to
      prove the etiologic role of CoQ10 deficiency in statin-associated myopathy and
      that large, well-designed clinical trials are required to address this issue. The
      routine use of CoQ10 cannot be recommended in statin-treated patients.
      Nevertheless, there are no known risks to this supplement and there is some
      anecdotal and preliminary trial evidence of its effectiveness. Consequently,
      CoQ10 can be tested in patients requiring statin treatment, who develop statin
      myalgia, and who cannot be satisfactorily treated with other agents. Some
      patients may respond, if only via a placebo effect.

PMID- 17560287
TI  - Percutaneous coronary intervention in patients receiving enoxaparin or
      unfractionated heparin after fibrinolytic therapy for ST-segment elevation
      myocardial infarction in the ExTRACT-TIMI 25 trial.
AB  - OBJECTIVES: We sought to evaluate whether enoxaparin (ENOX) is superior to
      unfractionated heparin (UFH) as adjunctive therapy for patients with ST-segment
      elevation myocardial infarction (STEMI) who receive fibrinolytic therapy and
      subsequently undergo percutaneous coronary intervention (PCI) by analyzing data
      from the ExTRACT-TIMI 25 (Enoxaparin and Thrombolysis Reperfusion for Acute
      Myocardial Infarction Treatment-Thrombolysis In Myocardial Infarction 25) trial.
      BACKGROUND: Limited data are available on the use of ENOX compared with UFH as
      adjunctive therapy in STEMI patients treated with fibrinolytic therapy and
      subsequent PCI. METHODS: A total of 20,479 STEMI patients who received
      fibrinolytic therapy were randomized to a strategy of ENOX throughout index
      hospitalization or UFH for at least 48 h, with blinded study drug to continue if
      PCI was performed. The primary end point of death or recurrent MI through 30 days
      was compared for ENOX versus UFH among the patients who underwent subsequent PCI
      (n = 4,676). RESULTS: After initial fibrinolysis, fewer patients underwent PCI
      through 30 days in the ENOX versus the UFH group (22.8% vs. 24.2%; p = 0.027).
      Among patients who underwent PCI by 30 days, the primary end point occurred in
      10.7% of ENOX and 13.8% of UFH patients (0.77 relative risk; p < 0.001). There
      were no differences in major bleeding for ENOX versus UFH (1.4% vs. 1.6%; p =
      NS). Results were similar when PCI was carried out in patients receiving blinded
      study drug during PCI (n = 2,178). CONCLUSION: Among patients treated with
      fibrinolytic therapy for STEMI who underwent subsequent PCI, ENOX administration
      was associated with a reduced risk of death or recurrent MI without difference in
      the risk of major bleeding. The strategy of ENOX support for fibrinolytic therapy
      followed by PCI is superior to UFH and provides a seamless transition from the
      medical management to the interventional management phase of STEMI without the
      need for introducing a second anticoagulant in the cardiac catheterization
      laboratory.

PMID- 17560288
TI  - Substitution of fractionated for unfractionated heparin during high-risk
      percutaneous coronary intervention: has the problem been solved?

PMID- 17560289
TI  - The impact of renal dysfunction on outcomes in the ExTRACT-TIMI 25 trial.
AB  - OBJECTIVES: The ExTRACT-TIMI 25 (Enoxaparin and Thrombolysis Reperfusion for
      Acute Myocardial Infarction Treatment-Thrombolysis In Myocardial Infarction 25)
      trial provided the opportunity to evaluate the impact of renal dysfunction on
      outcomes in patients with ST-segment elevation myocardial infarction (STEMI) and
      compare enoxaparin (ENOX) and unfractionated heparin (UFH). BACKGROUND: It is
      unclear how renal dysfunction influences the balance between benefit and risk of
      antithrombotic therapy. METHODS: In the ExTRACT-TIMI 25 trial, 20,479 patients
      were randomized to UFH or ENOX. A reduced ENOX dose was administered to patients
      age > or =75 years and those with an estimated creatinine clearance (CrCl) <30
      ml/min. RESULTS: A powerful relationship was observed between the severity of
      renal dysfunction (per 10 ml/min decrement in CrCl) and death, stroke,
      intracranial hemorrhage, and major and minor bleeding (p < 0.001 for each). There
      was a progressive increase in the treatment benefit with ENOX on death or
      nonfatal myocardial infarction (p < 0.01) with better renal function. Net
      clinical benefit (death, nonfatal MI, or nonfatal major bleeding) was
      significantly superior with ENOX (p < 0.001) for patients with a CrCl >60 ml/min
      (79.1% of the study population). Major bleeding and intracranial hemorrhage did
      not differ for patients with preserved renal function (CrCl >90 ml/min), but in
      those with renal dysfunction there was a progressively greater increase in the
      risk of major and minor bleeding with ENOX. CONCLUSIONS: Enoxaparin was superior
      to UFH for the majority of subjects. With more severe renal dysfunction, the net
      clinical benefit between ENOX and UFH did not differ, despite the rise in adverse
      events in both treatment groups. Future studies should take renal dysfunction
      into account when assessing antithrombotic regimens.

PMID- 17560290
TI  - Efficacy and safety of enoxaparin versus unfractionated heparin in patients with
      ST-segment elevation myocardial infarction also treated with clopidogrel.
AB  - OBJECTIVES: The purpose of this study was to determine the efficacy and safety of
      enoxaparin (ENOX) versus unfractionated heparin (UFH) in patients with ST-segment
      elevation myocardial infarction (STEMI) receiving fibrinolytic therapy with and
      without clopidogrel. BACKGROUND: The efficacy and safety of ENOX and clopidogrel
      given together in STEMI remains to be defined. METHODS: We compared the rates of
      major adverse cardiovascular events (MACE) as well as the rates of bleeding in
      medically managed patients randomized to ENOX versus UFH in the ExTRACT-TIMI 25
      (Enoxaparin and Thrombolysis Reperfusion for Acute Myocardial Infarction
      Treatment-Thrombolysis In Myocardial Infarction 25) trial, stratified by
      concomitant clopidogrel use. RESULTS: Enoxaparin significantly reduced the rate
      of the composite of death, recurrent myocardial infarction, myocardial ischemia,
      or stroke, compared with UFH, both in patients (n = 2,173) treated with
      clopidogrel (10.8% vs. 13.9%, adjusted odds ratio [OR(adj)] 0.70, p = 0.013) and
      in patients (n = 12,918) not treated with clopidogrel (13.3% vs. 15.3%, OR(adj)
      0.85, p = 0.003) with no evidence of heterogeneity (p(interaction) = 0.21). The
      excess risk of TIMI major bleeding with ENOX versus UFH was numerically but not
      statistically significantly higher in patients treated with clopidogrel (2.7% vs.
      1.0%) versus those who were not (2.1% vs. 1.2%) (p(interaction) = 0.61). Net
      clinical benefit (MACE and major bleeding) favored treatment with ENOX over UFH,
      either with concomitant clopidogrel (absolute risk reduction 2.4%, 95% confidence
      interval [CI] -0.5% to 5.3%) or without (absolute risk reduction 1.7%, 95% CI
      0.5% to 3.0%) (p(interaction) = 0.61). CONCLUSIONS: In patients with STEMI
      receiving fibrinolytic therapy, the net benefit of ENOX is similar in patients
      who are and are not treated with clopidogrel. The totality of trial data suggest
      that the combination of a fibrinolytic, aspirin, clopidogrel, and ENOX offers an
      attractive pharmacologic reperfusion strategy in STEMI.

PMID- 17560291
TI  - Correlation between morphologic characteristics and local temperature differences
      in culprit lesions of patients with symptomatic coronary artery disease.
AB  - OBJECTIVES: The purpose of this study was to investigate the possible correlation
      between morphologic and functional characteristics of culprit lesions (CL) in
      patients with acute coronary syndromes (ACS) and chronic stable angina (CSA).
      BACKGROUND: Intravascular ultrasound (IVUS) provides morphologic assessment and
      intracoronary thermography (ICT) evaluates the local inflammatory activation of
      CL. METHODS: Eighty-one consecutive patients, 48 with ACS and 33 with CSA, were
      enrolled. Ratio of lesion to reference external elastic membrane area, indicated
      by IVUS, was defined as positive remodeling index (pRi) (> or =1) or negative
      remodeling index (nRi) (<1). We also investigated the existence of ruptured
      plaque (rp) in the CL. By ICT temperature difference (DeltaT) between the CL and
      the proximal vessel wall was measured. RESULTS: Patients with ACS had greater
      remodeling index than patients with CSA (1.15 +/- 0.18 vs. 0.90 +/- 0.12; p <
      0.01), as well as increased DeltaT (0.08 +/- 0.03 degrees C vs. 0.04 +/- 0.02
      degrees C; p < 0.01). Patients with pRi had higher DeltaT than patients with nRi
      (0.07 +/- 0.03 degrees C vs. 0.04 +/- 0.02 degrees C; p < 0.001). In patients
      with nRi there was no difference in DeltaT between ACS and CSA (p = 0.22).
      Patients with rp had increased DeltaT compared with patients without rp (0.09 +/-
      0.03 degrees C vs. 0.05 +/- 0.02 degrees C; p < 0.01). Multivariate analysis
      showed that DeltaT was independently correlated with the presence of rp, pRi, and
      ACS. CONCLUSIONS: The present study showed that culprit lesions with plaque
      rupture and positive arterial remodeling have increased thermal heterogeneity,
      although in certain patients a discrepancy between morphogic and functional
      characteristics was observed. A combination of morphologic and functional
      examination may offer additional diagnostic and prognostic information.

PMID- 17560292
TI  - Plaque temperature, arterial remodeling, and inflammation: understanding "hot
      spots" in the coronary arteries.

PMID- 17560294
TI  - Evolving trends in the use of echocardiography: a study of Medicare
      beneficiaries.
AB  - OBJECTIVES: We studied the use of echocardiography among Medicare beneficiaries
      between 1999 and 2004 to determine the rate of growth in these services and
      evaluate the drivers of growth. BACKGROUND: Concerned about increasing health
      care costs, federal and private payers have highlighted growth in diagnostic
      imaging studies and begun to develop approaches to curb this growth. METHODS:
      Medicare Part B Physician/Supplier Procedure Summary Master File and enrollment
      data from 1999 to 2004 were reviewed. Total Medicare carrier-paid spending for
      echocardiography services was determined from procedure volumes and allowed
      charges. The 5% standard analytic file of physician claims was used to evaluate
      geographic variations in use and to document the specialties of physicians who
      request and those who interpret echocardiograms. RESULTS: Between 1999 and 2004,
      echocardiography services grew at a rate similar to that for all medical services
      subject to Medicare's sustainable growth rate (SGR) calculation. Increasing
      provision of echocardiograms in physicians' offices contributed to increased
      spending under the SGR. Accounting for this shift, actual annualized per capita
      growth in echocardiography was 7.7%. Variations in the prevalence of heart
      disease contributed to geographic variations in use. Although cardiologists were
      the most common providers of echocardiographic services, primary care physicians
      ordered the majority of these diagnostic procedures. CONCLUSIONS: Growth in the
      use of echocardiography is in keeping with the general growth in medical
      services. Nonetheless, physicians who order echocardiograms and those who provide
      them must work together to ensure that in the future these diagnostic services
      are used appropriately and not excessively.

PMID- 17560293
TI  - Asymmetric dimethylarginine determines the improvement of endothelium-dependent
      vasodilation by simvastatin: Effect of combination with oral L-arginine.
AB  - OBJECTIVES: We hypothesized that the level of asymmetric dimethylarginine (ADMA),
      an endogenous inhibitor of endothelial nitric oxide (NO) synthase (eNOS), might
      determine the endothelial effects of statins. BACKGROUND: Endothelial NO synthase
      is up-regulated by statins. However, statins failed to improve endothelial
      function in some studies. Asymmetric dimethylarginine inhibits eNOS by a
      mechanism that is reversible by L-arginine. METHODS: Ninety-eight clinically
      asymptomatic elderly subjects had their plasma ADMA levels screened. Those in the
      highest (high ADMA, n = 15) and lowest quartiles of the ADMA distribution (low
      ADMA, n = 13) were eligible to receive, in a randomized order, simvastatin (40
      mg/day), L-arginine (3 g/day), or a combination of both, each for 3 weeks.
      Endothelium-dependent vasodilation (EDD) was assessed by brachial artery
      ultrasound. RESULTS: Simvastatin had no effect on EDD in subjects with high ADMA
      (6.2 +/- 1.2% vs. 6.1 +/- 0.9%), whereas simvastatin plus L-arginine
      significantly improved EDD (9.8 +/- 1.5% vs. 5.3 +/- 0.8%; p < 0.01). In subjects
      with low ADMA, simvastatin improved endothelial function when given alone (9.5 +/
      3.2% vs. 6.1 +/- 3.8%; p < 0.001) or in combination with L-arginine (9.0 +/-
      3.1% vs. 6.3 +/- 3.3%; p = 0.001). L-arginine alone improved endothelial function
      in both groups. Endothelium-independent vasodilation was not affected.
      CONCLUSIONS: Simvastatin does not enhance endothelial function in subjects with
      elevated ADMA, whereas it does so in patients with low ADMA. Combination of
      simvastatin with oral L-arginine improves endothelial function in subjects with
      high ADMA, but has no additional effect in subjects with low ADMA. As NO-mediated
      effects may play a major role in the therapeutic effects of statins, ADMA
      concentration is an important factor that influences the "pleiotropic" effects of
      simvastatin.

PMID- 17560296
TI  - Anemia in patients with advanced heart failure.

PMID- 17560295
TI  - An elastic, biodegradable cardiac patch induces contractile smooth muscle and
      improves cardiac remodeling and function in subacute myocardial infarction.
AB  - OBJECTIVES: Our objective in this study was to apply an elastic, biodegradable
      polyester urethane urea (PEUU) cardiac patch onto subacute infarcts and to
      examine the resulting cardiac ventricular remodeling and performance. BACKGROUND:
      Myocardial infarction induces loss of contractile mass and scar formation
      resulting in adverse left ventricular (LV) remodeling and subsequent severe
      dysfunction. METHODS: Lewis rats underwent proximal left coronary ligation. Two
      weeks after coronary ligation, a 6-mm diameter microporous PEUU patch was
      implanted directly on the infarcted LV wall surface (PEUU patch group, n = 14).
      Sham surgery was performed as an infarction control (n = 12). The LV contractile
      function, regional myocardial wall compliance, and tissue histology were assessed
      8 weeks after patch implantation. RESULTS: The end-diastolic LV cavity area (EDA)
      did not change, and the fractional area change (FAC) increased in the PEUU patch
      group (p < 0.05 vs. week 0), while EDA increased and FAC decreased in the
      infarction control group (p < 0.05). The PEUU patch was largely resorbed 8 weeks
      after implantation and the LV wall was thicker than infarction control (p < 0.05
      vs. control group). Abundant smooth muscle bundles with mature contractile
      phenotype were found in the infarcted myocardium of the PEUU group. The
      myocardial compliance of the PEUU group was distributed between normal myocardium
      and infarction control (p < 0.001). CONCLUSIONS: Implantation of a novel
      biodegradable PEUU patch onto a subacute myocardial infarction promoted
      contractile phenotype smooth muscle tissue formation and improved cardiac
      remodeling and contractile function at the chronic stage. Our findings suggest a
      new therapeutic option against post-infarct cardiac failure.

PMID- 17560297
TI  - Is anemia in chronic heart failure caused by iron deficiency?

PMID- 17560299
TI  - Sarcoidosis.

PMID- 17560300
TI  - Sarcoidosis: a historical perspective.

PMID- 17560301
TI  - Genetics of sarcoidosis.
AB  - The predisposition to sarcoidosis is genetically determined, and genetics appears
      also to account for the variability in clinical phenotype and behaviour. Many
      genetic loci have been investigated to date, mainly in case-control association
      studies. However, only a small number of human leukocyte antigen (HLA) alleles
      have been consistently associated with sarcoidosis susceptibility/phenotype. In
      this regard, the association between Lofgren's syndrome and the extended HLA
      DRB1*0301/DQB1*0201 haplotype is probably the most extensively reproduced.
      Several, generally less convincing, associations have been also reported. Of
      these, the chemokine receptor and butyrophilin-like 2 (BTNL2) associations are
      most promising. However, two major limitations of genetic studies are that the
      understanding of the biological relevance of gene variations in the genome is
      still incomplete and that the reported associations need to be verified in
      populations of different ethnicities. Despite a number of intriguing hypotheses,
      what causes sarcoidosis remains obscure. Genetic studies and, importantly,
      functional analysis of candidate genes will provide insight into pathogenesis and
      disease risk. However, if, as many believe, sarcoidosis is a heterogeneous
      collection of disorders, a critical step will be to carefully refine the clinical
      phenotype, as genetic studies of complex diseases are more rewording if a very
      specific disease subset is addressed.

PMID- 17560302
TI  - Immunopathogenesis of sarcoidosis.
AB  - The immunopathogenesis of sarcoidosis has been difficult to charaterize given the
      heterogeneity of disease, the elusiveness of the causative antigen, and the lack
      of an adequate animal model. However, by examining well-defined clinical cohorts,
      the interplay between genetic predisposition and immunologic response has been
      increasingly informative. Technological advances in cellular analysis have
      allowed researchers to characterize the immune responses important in the
      maintenance of granulomatous inflammation. Finally, "new" clinical observations
      such as granuloma responsiveness to targeted biological therapies, sarcoid
      developing during immune restoration, and the relationship between sarcoidosis
      and Hepatitis C will provide future insight to the immunopathogenesis of
      sarcoidosis.

PMID- 17560303
TI  - Considering an infectious etiology of sarcoidosis.
AB  - Sarcoidosis is a systemic granulomatous disease of unknown cause. An infectious
      etiology of sarcoidosis has long been suspected, but only recently has scientific
      evidence provided a strong link between infectious agents and sarcoidosis.
      Moreover, recent advances in our understanding of the relationships between
      sarcoidosis phenotype and host genetic factors may further illuminate the
      mechanisms linking infection and sarcoidosis.

PMID- 17560304
TI  - Gene-environment interactions in sarcoidosis: challenge and opportunity.
AB  - Susceptibility to most human diseases is polygenic, with complex interactions
      between functional polymorphisms of single genes governing disease incidence,
      phenotype, or both. In this context, the contribution of any discrete gene is
      generally modest for a single individual, but may confer substantial attributable
      risk on a population level. Environmental exposure can modify the effects of a
      polymorphism, either by providing a necessary substrate for development of human
      disease or because the effects of a given exposure modulate the effects of the
      gene. In several diseases, genetic polymorphisms have been shown to be context
      dependent, ie, the effects of a genetic variant are realized only in the setting
      of a relevant exposure. Because sarcoidosis susceptibility is dependent on both
      genetic and environmental modifiers, the study of gene-environment interactions
      may yield important pathogenetic information and will likely be crucial for
      uncovering the range of genetic susceptibility loci. The complexity of these
      relationships implies, however, that investigations of gene-environment
      interactions will require the study of large cohorts with carefully defined
      exposures and similar clinical phenotypes. A general principle is that the study
      of gene-environment interactions requires a sample size at least severalfold
      greater than for either factor alone. To date, the presence of environmental
      modifiers has been demonstrated for one sarcoidosis susceptibility locus, HLA
      DQB1, in African-American families. This article reviews general considerations
      obtaining for the study of gene-environment interactions in sarcoidosis. It also
      describes the limited current understanding of the role of environmental
      influences on sarcoidosis susceptibility genes.

PMID- 17560305
TI  - Cutaneous sarcoidosis: differential diagnosis.
AB  - Sarcoidosis is a multisystem disease with cutaneous lesions present in 20%-35% of
      patients. Given the wide variability of clinical manifestations, it is one of the
      "great imitators," making it necessary to consider clinical, epidemiological,
      radiographic, laboratory, and histopathological criteria to make the diagnosis.
      Cutaneous lesions have been classified as specific and nonspecific, depending on
      the presence of noncaseating granulomas on histologic studies. Specific lesions
      include maculopapules, plaques, nodules, lupus pernio, scar infiltration,
      alopecia, ulcerative lesions, and hypopigmentation among others. Nail, mucosal,
      and childhood sarcoidosis represent a distinct subset of the disease process. The
      most common nonspecific lesion is erythema nodosum. Others include
      calcifications, prurigo, erythema multiforme, nail clubbing, and Sweet syndrome.
      The importance of considering cutaneous sarcoidosis in the clinical differential
      diagnosis of a given skin lesion relies on the association with systemic
      involvement and the convenience of the skin as a tissue source for histologic
      analysis.

PMID- 17560306
TI  - Erythema nodosum.
AB  - Erythema nodosum (EN) is the most common form of panniculitis. It is
      characterized by the presence of rounded or oval, slightly raised, nonulcerative
      painful red nodules in the skin and subcutaneous fatty tissue, 1 to 6 cm in
      diameter, sometimes coalescing. They tend to be symmetrical in distribution and
      are usually located bilaterally on the lower extremities, particularly on the
      anterior tibial surface, although they may also involve the ankles, the lower
      parts of the thighs, and the forearms.

PMID- 17560307
TI  - Chronic cutaneous lesions of sarcoidosis.
AB  - Sarcoidosis involvement of the skin is common. The skin lesions of sarcoidosis
      may be nonspecific, showing a nondiagnostic inflammatory reaction pattern on
      histologic evaluation. Nonspecific skin lesions are often associated with an
      acute presentation of sarcoidosis and, in general, portend a good prognosis.
      Specific sarcoidosis skin lesions reveal typical sarcoid granulomas on histologic
      examination. These lesions tend to be chronic and require therapy for resolution.
      This article will review the epidemiology, diagnostic evaluation, and description
      of the various chronic skin lesions of sarcoidosis. Various images of these skin
      lesions will be demonstrated.

PMID- 17560308
TI  - Systemic evaluation of a potential cutaneous sarcoidosis patient.
AB  - The diagnosis of sarcoidosis cannot be established by the presence of granuloma
      in a single organ, such as the skin. Therefore, the patient with potential
      cutaneous sarcoidosis should undergo a systemic evaluation for two reasons: to
      help confirm the diagnosis, and to identify other potential problems. This
      article reviews the recommended testing in patients with suspected or known
      sarcoidosis. The evaluation leads to a wide number of organs being assessed by
      either history, physical examination or routine laboratory investigations. The
      major organs routinely assessed are the lungs, the eyes, the liver and the heart.

PMID- 17560309
TI  - Radiological manifestations of sarcoidosis.
AB  - Sarcoidosis is an immune system disorder characterised by non-necrotising
      granulomas. Pulmonary involvement is the most common presentation of sarcoidosis,
      but it can manifest in any organ. Other commonly involved organ systems include
      the lymph nodes (especially the intrathoracic nodes); the skin; the eyes; the
      liver; the heart; and the nervous, musculoskeletal, renal, and endocrine systems.
      The typical and atypical imaging features of multisystemic involvement of
      sarcoidosis have been discussed with review of the gamut of radiological
      manifestations of thoracic, cardiac, CNS, abdominal and musculoskeletal
      sarcoidosis.

PMID- 17560310
TI  - Sarcoidosis and malignancy.
AB  - Malignancy in patients with sarcoidosis occurs in 3 settings. The first setting
      relates to patients with hematologic malignancies. It includes the sarcoidosis
      lymphoma syndrome, which refers to the development of lymphoma at least 1 to 2
      years after the diagnosis of sarcoidosis. It also includes patients with
      sarcoidosis who develop other hematologic malignancies. In addition, this subset
      of individuals includes patients with cancer and hematologic malignancies who
      subsequently develop sarcoidosis. The second setting consists of patients with
      sarcoidosis who develop solid tumors and oncologic patients in whom sarcoidosis
      subsequently appears; in addition to melanoma and nonmelanoma skin cancer, the
      neoplasms most commonly associated involve the cervix, liver, lung, testicles,
      and uterus. The third setting of malignancy-related sarcoidosis occurs when
      sarcoidosis presents as a paraneoplastic syndrome for the associated cancer,
      specifically when the discovery of cancer is concurrent with or within 1 year of
      the diagnosis of sarcoidosis or vis-a-vis. Antineoplastic treatment of either the
      hematologic malignancy or the solid tumor has also been observed to either induce
      the initial onset or flare the activity of sarcoidosis. Malignancy can also be
      associated with the occurrence of sarcoid reactions that typically are restricted
      to the regional lymph nodes or the visceral organ of tumor origin; rarely, the
      sarcoid reaction can also be observed in the skin or is only limited to the skin.

PMID- 17560311
TI  - Evidence-based therapy for cutaneous sarcoidosis.
AB  - Most of treatments for cutaneous sarcoidosis are extensions of the drugs tested
      for pulmonary sarcoidosis. There are some exceptions. These include drugs given
      topically and those with high concentrations in the skin. This review will
      examine the conventional treatments of cutaneous sarcoidosis and focus on the
      best available evidence to make recommendations on treatment.

PMID- 17560312
TI  - Sarcoidosis, role of tumor necrosis factor inhibitors and other biologic agents,
      past, present, and future concepts.
AB  - Tumor necrosis factor is a potent cytokine involved in the inflammatory process
      of many diseases. Agents that block tumor necrosis factor have been used in the
      treatment of various immune-mediated diseases, including rheumatoid arthritis,
      Crohn disease, psoriatic arthritis, and ankylosing spondylitis. Sarcoidosis is an
      immune-mediated inflammatory disorder of unknown etiology characterized by the
      formation of noncaseating granulomas. Tumor necrosis factor plays a major role in
      the inflammatory process seen in sarcoidosis. Sarcoidosis therapies with activity
      against tumor necrosis factor and specific anti-tumor necrosis factor therapies
      have been used with variable success. The long-term safety and efficacy of such
      therapies are yet to be determined in well-designed clinical trials with long
      term follow-up.

PMID- 17560313
TI  - In the pursuit of classifying severe cutaneous adverse reactions.
AB  - We suggest adding an additional type of lesion to the existing 4 types of lesions
      of the erythema multiforme (EM), Stevens-Johnson syndrome (SJS), and toxic
      epidermal necrolysis (TEN), namely "flat typical target" and call the original
      typical targets "raised typical target." The EM group would consist of raised
      typical targets and raised atypical targets, similar to the original definition,
      and the SJS/TEN group would consist of flat typical targets, flat atypical
      targets and macules with or without blisters. In our proposed modified
      classification (Table 1), all the lesions that are found in the EM group are
      raised, whereas all lesions that characterize the SJS/TEN group are flat, even
      though they have blisters on them.

PMID- 17560314
TI  - I have good news! You have leukemia.

PMID- 17560316
TI  - Philip C. Anderson, MD (1930-2000).

PMID- 17560317
TI  - Natural product research: the challenges facing the modern researcher.

PMID- 17560318
TI  - Screening methods used to determine the anti-microbial properties of Aloe vera
      inner gel.
AB  - The emergence of antibiotic resistant bacterial strains is a growing problem and
      is an important concern for patients, physicians, healthcare managers, and
      policymakers as it results in poorer health and economic outcomes. This has led
      to an urgent global call for new antimicrobial drugs, particularly from natural
      resources. We have been studying the antimicrobial properties of the inner leaf
      gel component of Aloe barbadensis Miller and have used a number of different,
      simple in vitro assays to establish a scientific basis for the potential use of
      Aloe vera on a range of clinically relevant bacteria. The bacteria used include
      Shigella flexneri, Methicillin-Resistant Staphylococcus aureus (MRSA),
      Enterobacter cloacae and Enterococcus bovis. In this paper, we compare standard
      methods recommended by the Clinical and Laboratory Standards Institute (CLSI)
      with a microtitre assay using a metabolic colour indicator Alamar blue. All the
      techniques described have shown that Aloe vera has an antimicrobial effect,
      however, the microtitre assay enables high throughput screening, under similar
      conditions and is less wasteful of plant material.

PMID- 17560319
TI  - Microtitre plate-based antibacterial assay incorporating resazurin as an
      indicator of cell growth, and its application in the in vitro antibacterial
      screening of phytochemicals.
AB  - The resazurin assay utilising microtitre-plate, described by Drummond and Waigh
      in 2000, has been modified to achieve more accuracy in the determination of the
      minimum inhibitory concentration (MIC) values of natural products, including
      crude extracts, chromatographic fractions or purified compounds against various
      bacterial strains. This modified resazurin method is simple, sensitive, rapid,
      robust and reliable, and could be used successfully to assess antibacterial
      properties of natural products.

PMID- 17560320
TI  - Colorimetric broth microdilution method for the antifungal screening of plant
      extracts against yeasts.
AB  - Screening plant extracts for antifungal activity is increasing due to demand for
      new antifungal agents, but the testing methods present many challenges. Standard
      broth microdilution methods for antifungal susceptibility testing of available
      antifungal agents are available now, but these methods are optimised for single
      compounds instead of crude plant extracts. In this study we evaluated the
      standard NCCLS method as well as a modification which uses spectrophotometric
      determination of the end-points with a plate reader. We also evaluated another
      standard method, the EUCAST method, which is a similar microdilution assay to the
      NCCLS method, but uses a larger inoculum size and a higher glucose concentration
      in the medium as well as spectrophotometric end-point determination. The results
      showed that all three methods had some drawbacks for testing plant extracts and
      thus we modified the NCCLS broth microdilution method by including a colorimetric
      indicator-resazurin for end-point determination. This modified method showed good
      reproducibility and clear-cut end-point, plus the end-point determination needed
      no instruments. It enabled us to evaluate the activity of a selection of extracts
      from six Combretaceous plants against three Candida spp. and thus provided
      pharmacological evidence for some traditional uses of these plants while
      assisting the identification of the active ingredients.

PMID- 17560321
TI  - In vitro testing of anthelmintic efficacy of Flemingia vestita (Fabaceae) on
      carbohydrate metabolism in Rallietina echinobothrida.
AB  - The root tuber peel of Flemingia vestita has been in use in local traditional
      medicine against intestinal worm infections in Meghalaya (North-East India). In
      order to evaluate and authenticate the anthelminitc efficacy of the isoflavones
      of F. vestita, the root peel extract of this putative plant was tested against
      several helminth parasites, extensively on Rallietina echinobothrida, with
      respect to different parameters of these parasites. In this paper, we describe
      various methods to evaluate the anthelmintic efficacy of this medicinal plant
      with respect to carbohydrate metabolism in R. echinobothrida at paralytic time
      caused by the isoflavones of F. vestita. To meet the high energy demand by the
      parasite due to the anthelmintic stress, glucose breakdown follows the PEPCK
      malate pathway in the parasite.

PMID- 17560322
TI  - The effect of blueberry extracts on Giardia duodenalis viability and spontaneous
      excystation of Cryptosporidium parvum oocysts, in vitro.
AB  - The protozoan parasites Giardia duodenalis and Cryptosporidium parvum are common
      causes of diarrhoea, worldwide. Effective drug treatment is available for G.
      duodenalis, but with anecdotal evidence of resistance or reduced compliance.
      There is no effective specific chemotherapeutic intervention for Cryptosporidium.
      Recently, there has been renewed interest in the antimicrobial properties of
      berries and their phenolic compounds but little work has been done on their
      antiparasitic actions. The effect of various preparations of blueberry (Vaccinium
      myrtillus) extract on G. duodenalis trophozoites and C. parvum oocysts were
      investigated. Pressed blueberry extract, a polyphenolic-rich blueberry extract,
      and a commercially produced blueberry drink (Bouvrage) all demonstrated
      antigiardial activity. The polyphenol-rich blueberry extract reduced trophozoite
      viability in a dose dependent manner. At 167 microgml(-1), this extract performed
      as well as all dilutions of pressed blueberry extract and the Bouvrage beverage
      (9.6+/-2.8% live trophozoites remaining after 24h incubation). The lowest
      dilution of blueberry extract tested (12.5% v/v) contained >167 microgml(-1) of
      polyphenolic compounds suggesting that polyphenols are responsible for the
      reduced survival of G. duodenalis trophozoites. The pressed blueberry extract,
      Bouvrage beverage and the polyphenolic-rich blueberry extract increased the
      spontaneous excystation of C. parvum oocysts at 37 degrees C, compared to
      controls, but only at a dilution of 50% Bouvrage beverage, equivalent to 213
      microgml(-1) gallic acid equivalents in the polyphenolic-rich blueberry extract.
      Above this level, spontaneous excystation is decreased. We conclude that water
      soluble extracts of blueberries can kill G. duodenalis trophozoites and modify
      the morphology of G. duodenalis and C. parvum.

PMID- 17560323
TI  - Strategies for transformation of naturally-occurring amphibian antimicrobial
      peptides into therapeutically valuable anti-infective agents.
AB  - The emergence of strains of pathogenic microorganisms with resistance to commonly
      used antibiotics has necessitated a search for novel types of antimicrobial
      agents. Many frog species produce amphipathic alpha-helical peptides with broad
      spectrum antimicrobial activity in the skin but their therapeutic potential is
      limited by varying degrees of cytolytic activity towards eukaryotic cells.
      Methods for development of such peptides into anti-infective drugs are
      illustrated by the example of temporin-1DRa (HFLGTLVNLAK KIL.NH(2)). Studies with
      model alpha-helical peptides have shown that increase in cationicity promotes
      antimicrobial activity whereas increases in hydrophobicity, helicity and
      amphipathicity promote hemolytic activity and loss of selectivity for
      microorganisms. Analogs of temporin-1DRa in which each amino acid is replaced by
      L-lysine and D-lysine were synthesized and their cytolytic activities tested
      against a range of microorganisms and human erythrocytes. Small changes in
      structure produced marked changes in conformation, as determined by retention
      time on reversed-phase HPLC, and in biological activity. However, peptides
      containing the substitutions (Val(7) -->L-Lys), (Thr(5)-->D-Lys) and (Asn(8)-->D
      Lys) retained the high solubility and potent, broad spectrum antimicrobial
      activity of the naturally occurring peptide but were appreciably (up to 10-fold)
      less hemolytic. In contrast, analogs in which Leu(9) and Ile(13) were replaced by
      the more hydrophobic cyclohexylglycine residue showed slightly increased
      antimicrobial potencies (up to 2-fold) but a 4-fold increase in hemolytic
      activity. The data suggest a strategy of selective increases in cationicity
      concomitant with decreases in helicity and hydrophobicity in the transformation
      of naturally-occurring antimicrobial peptides into non-toxic therapeutic agents.

PMID- 17560324
TI  - Biomedicinals from the phytosymbionts of marine invertebrates: a molecular
      approach.
AB  - Marine invertebrate animals such as sponges, gorgonians, tunicates and bryozoans
      are sources of biomedicinally relevant natural products, a small but growing
      number of which are advancing through clinical trials. Most metazoan and
      anthozoan species harbour commensal microorganisms that include prokaryotic
      bacteria, cyanobacteria (blue-green algae), eukaryotic microalgae, and fungi
      within host tissues where they reside as extra- and intra-cellular symbionts. In
      some sponges these associated microbes may constitute as much as 40% of the
      holobiont volume. There is now abundant evidence to suggest that a significant
      portion of the bioactive metabolites thought originally to be products of the
      source animal are often synthesized by their symbiotic microbiota. Several anti
      cancer metabolites from marine sponges that have progressed to pre-clinical or
      clinical-trial phases, such as discodermolide, halichondrin B and bryostatin 1,
      are thought to be products derived from their microbiotic consortia. Freshwater
      and marine cyanobacteria are well recognised for producing numerous and
      structurally diverse bioactive and cytotoxic secondary metabolites suited to drug
      discovery. Sea sponges often contain dominant taxa-specific populations of
      cyanobacteria, and it is these phytosymbionts (= photosymbionts) that are
      considered to be the true biogenic source of a number of pharmacologically active
      polyketides and nonribosomally synthesized peptides produced within the sponge.
      Accordingly, new collections can be pre-screened in the field for the presence of
      phytobionts and, together with metagenomic screening using degenerate PCR primers
      to identify key polyketide synthase (PKS) and nonribosomal peptide synthetase
      (NRPS) genes, afford a biodiscovery rationale based on the therapeutic prospects
      of phytochemical selection. Additionally, new cloning and biosynthetic expression
      strategies may provide a sustainable method for the supply of new pharmaceuticals
      derived from the uncultured phytosymbionts of marine organisms.

PMID- 17560325
TI  - The sulphorhodamine (SRB) assay and other approaches to testing plant extracts
      and derived compounds for activities related to reputed anticancer activity.
AB  - Since the major approach in searching for potential anticancer agents over the
      last 50 years has been based on selective cytotoxic effects on mammalian cancer
      cell lines, cell-based methods for cytotoxicity are described and compared. The
      sulphorhodamine B (SRB) assay is described in detail as the preferred method and
      also a novel approach has been developed which is based on the hypothesis that,
      in some circumstances, the naturally occurring compounds act as prodrugs rather
      than active compounds in their own right. Consequently, extracts or compounds are
      pre-incubated with systems modelling metabolic processes in the body before being
      tested. The methods have been validated using known compounds and Iris tectorum
      extracts have been shown to be more cytotoxic after treatment with beta
      glucosidase. In addition bioassays based on mammalian cells involving antioxidant
      and upregulation of some cellular self-defence mechanisms are discussed which are
      related to prevention as well as treatment of cancer. Extracts of Alpinia
      officinarum induced glutathione-S-transferase (GST) activity in cultured
      hepatocytes and this was traced to the phenylpropanoids present, especially 1'
      acetoxychavicol acetate.

PMID- 17560326
TI  - The inner gel component of Aloe vera suppresses bacterial-induced pro
      inflammatory cytokines from human immune cells.
AB  - The present study was carried out to examine the anti-inflammatory activity of
      the inner leaf gel component of Aloe barbadensis Miller. A simple in vitro assay
      was designed to determine the effect of the inner gel on bacterial-induced pro
      inflammatory cytokine production, namely TNF-alpha and IL-1 beta, from peripheral
      blood leukocytes stimulated with Shigella flexneri or LPS. This report describes
      the suppression of both cytokines with a freeze-dried inner gel powder and a
      commercial health drink from the same source. Comparison was made with a human
      monocytic cell-line (THP-1 cells) and a similar trend in responses was
      demonstrated.

PMID- 17560328
TI  - A CERTain role for ceramide in taxane-induced cell death.
AB  - An unexpected benefit of functional genomic screens is that at times they answer
      questions that they were not designed to ask. A siRNA screen reported by Swanton
      et al. in this issue of Cancer Cell reveals that silencing of spindle assembly
      checkpoint genes facilitates mitotic slippage, resulting in escape from taxane
      induced cell death, aneuploidy, and chromosomal instability, hallmarks of taxane
      resistance. Unexpectedly, the screen disclosed that the sphingolipid ceramide is
      a key regulator of the taxane-mediated spindle assembly checkpoint and taxane
      induced cell death. Ceramide metabolism thus serves as a legitimate target for
      modulation of taxane effect on tumors.

PMID- 17560329
TI  - Chromatin modulation by oncogenic transcription factors: new complexity, new
      therapeutic targets.
AB  - Oncogenic transcription factors such as PML-RARalpha, RUNX1-MTG8, and others work
      in large part by the recruitment of inhibitors of gene transcription to target
      promoters leading to aberrant repression of gene expression. PML-RARalpha, an
      archetypal chimeric oncoprotein, was previously shown to bring complexes of
      histone deacetylases (HDACs), histone methyltransferases (HMTases), and DNA
      methyl transferases (DNMTs) to target genes. In this issue of Cancer Cell, Villa
      et al. show that the full complement of chromatin machinery can be commandeered
      by these transcription factors with the polycomb group of proteins representing
      the newest identified recruit.

PMID- 17560330
TI  - The potential of new tumor endothelium-specific markers for the development of
      antivascular therapy.
AB  - Angiogenesis is a hallmark of solid tumors, and disruption of tumor vasculature
      is an active anticancer therapy in some cases. Several proteins expressed on the
      surface of tumor endothelium have been identified during the last decade.
      However, due to the expression in both physiological and tumor angiogenesis, only
      a few targets have been developed for clinical therapeutics. By thorough SAGE
      analysis of mouse endothelial cells isolated from various normal resting tissues,
      regenerating liver, and liver-metastasized tumor, Seaman and colleagues in this
      issue of Cancer Cell have demonstrated organ-specific endothelial markers,
      physiological angiogenesis endothelial markers, and tumor endothelial markers and
      revealed striking differences between physiological and pathological
      angiogenesis.

PMID- 17560331
TI  - Structural basis for recognition of SMRT/N-CoR by the MYND domain and its
      contribution to AML1/ETO's activity.
AB  - AML1/ETO results from the t(8;21) associated with 12%-15% of acute myeloid
      leukemia. The AML1/ETO MYND domain mediates interactions with the corepressors
      SMRT and N-CoR and contributes to AML1/ETO's ability to repress proliferation and
      differentiation of primary bone marrow cells as well as to enhance their self
      renewal in vitro. We solved the solution structure of the MYND domain and show it
      to be structurally homologous to the PHD and RING finger families of proteins. We
      also determined the solution structure of an MYND-SMRT peptide complex. We
      demonstrated that a single amino acid substitution that disrupts the interaction
      between the MYND domain and the SMRT peptide attenuated AML1/ETO's effects on
      proliferation, differentiation, and gene expression.

PMID- 17560332
TI  - Regulators of mitotic arrest and ceramide metabolism are determinants of
      sensitivity to paclitaxel and other chemotherapeutic drugs.
AB  - Cytotoxic drug resistance is a major cause of cancer treatment failure. We report
      an RNA interference screen to identify genes influencing sensitivity of different
      cancer cell types to chemotherapeutic agents. A set of genes whose targeting
      leads to resistance to paclitaxel is identified, many of which are involved in
      the spindle assembly checkpoint. Silencing these genes attenuates paclitaxel
      induced mitotic arrest and induces polyploidy in the absence of drug. We also
      identify a ceramide transport protein, COL4A3BP or CERT, whose downregulation
      sensitizes cancer cells to multiple cytotoxic agents, potentiating endoplasmic
      reticulum stress. COL4A3BP expression is increased in drug-resistant cell lines
      and in residual tumor following paclitaxel treatment of ovarian cancer,
      suggesting that it could be a target for chemotherapy-resistant cancers.

PMID- 17560333
TI  - Role of the polycomb repressive complex 2 in acute promyelocytic leukemia.
AB  - Epigenetic changes are common alterations in cancer cells. Here, we have
      investigated the role of Polycomb group proteins in the establishment and
      maintenance of the aberrant silencing of tumor suppressor genes during
      transformation induced by the leukemia-associated PML-RARalpha fusion protein. We
      show that in leukemic cells knockdown of SUZ12, a key component of Polycomb
      repressive complex 2 (PRC2), reverts not only histone modification but also
      induces DNA demethylation of PML-RARalpha target genes. This results in promoter
      reactivation and granulocytic differentiation. Importantly, the epigenetic
      alterations caused by PML-RARalpha can be reverted by retinoic acid treatment of
      primary blasts from leukemic patients. Our results demonstrate that the direct
      targeting of Polycomb group proteins by an oncogene plays a key role during
      carcinogenesis.

PMID- 17560334
TI  - Autologous chemotaxis as a mechanism of tumor cell homing to lymphatics via
      interstitial flow and autocrine CCR7 signaling.
AB  - CCR7 is implicated in lymph node metastasis of cancer, but its role is obscure.
      We report a mechanism explaining how interstitial flow caused by lymphatic
      drainage directs tumor cell migration by autocrine CCR7 signaling. Under static
      conditions, lymphatic endothelium induced CCR7-dependent chemotaxis of tumor
      cells through 3D matrices. However, interstitial flow induced strong increases in
      tumor cell migration that were also CCR7 dependent, but lymphatic independent.
      This autologous chemotaxis correlated with metastatic potential in four cell
      lines and was verified by visualizing directional polarization of cells in the
      flow direction. Computational modeling revealed that transcellular gradients of
      CCR7 ligand were created under flow to drive this response. This illustrates how
      tumor cells may be guided to lymphatics during metastasis.

PMID- 17560335
TI  - Genes that distinguish physiological and pathological angiogenesis.
AB  - To unravel the normal vasculature transcriptome and determine how it is altered
      by neighboring malignant cells, we compared gene expression patterns of
      endothelial cells derived from the blood vessels of eight normal resting tissues,
      five tumors, and regenerating liver. Organ-specific endothelial genes were
      readily identified, including 27 from brain. We also identified 25 transcripts
      overexpressed in tumor versus normal endothelium, including 13 that were not
      found in the angiogenic endothelium of regenerating liver. Most of the shared
      angiogenesis genes have expected roles in cell-cycle control, but those specific
      for tumor endothelium were primarily cell surface molecules of uncertain
      function. These studies reveal striking differences between physiological and
      pathological angiogenesis potentially important for the development of tumor
      specific, vascular-targeted therapies.

PMID- 17560336
TI  - Identification of the JNK signaling pathway as a functional target of the tumor
      suppressor PTEN.
AB  - Although most oncogenic phenotypes of PTEN loss are attributed to AKT activation,
      AKT alone is not sufficient to induce all of the biological activities associated
      with PTEN inactivation. We searched for additional PTEN-regulated pathways
      through gene set enrichment analysis (GSEA) and identified genes associated with
      JNK activation. PTEN null cells exhibit higher JNK activity, and genetic studies
      demonstrate that JNK functions parallel to and independently of AKT. Furthermore,
      PTEN deficiency sensitizes cells to JNK inhibition and negative feedback
      regulation of PI3K was impaired in PTEN null cells. Akt and JNK activation are
      highly correlated in human prostate cancer. These findings implicate JNK in PI3K
      driven cancers and demonstrate the utility of GSEA to identify functional
      pathways using genetically defined systems.

PMID- 17560337
TI  - PEAR lab and nonlocal mind: why they matter.

PMID- 17560338
TI  - From parapsychology to spirituality: the legacy of the PEAR database.

PMID- 17560342
TI  - The PEAR proposition.
AB  - For more than a quarter century, the Princeton Engineering Anomalies Research
      (PEAR) laboratory has engaged in a broad range of experiments on consciousness
      related physical anomalies and has proposed a corresponding selection of
      theoretical models that have combined to illuminate the fundamental nature of the
      provocative phenomena that emerge. Productive pursuit of this topic has
      inescapably involved a spectrum of political, cultural, personal, and
      interpersonal factors that are normally not encountered in more conventional
      scientific scholarship, but have both enriched and complicated the enterprise in
      many ways. Some of the insights gleaned from the work are objectively
      specifiable, such as the scale and structural character of the anomalous effects;
      their relative insensitivity to objective physical correlates, including distance
      and time; the oscillating sequential patterns of performance they display; the
      major discrepancies between male and female achievements; and their irregular
      replicability at all levels of experience. But many others relate to subjective
      issues, such as the responsiveness of the effects to conscious and unconscious
      intention and to individual and collective resonance; the relevance of ambience
      and attitude in their generation; and the importance of intrinsic uncertainty as
      a source of the anomalies. This blend of empirical features predicates radical
      excursions of the dedicated models, and hence of the more general scientific
      paradigms, to allow consciousness and its subjective information processing
      capacities a proactive role in the establishment of objective reality, with all
      of the complications of specificity, causality, and reproducibility that entails.
      The attendant complexities of conceptualization, formulation, and implementation
      notwithstanding, pragmatic applications of these phenomena in many sectors of
      public endeavor now can be foreseen.

PMID- 17560343
TI  - Information, consciousness, and health.
AB  - A 16-year empirical assessment of anomalous human/machine interactions provides
      strong evidence that consciousness can add information to otherwise random
      digital strings. A parallel program of remote perception studies establishes the
      inverse process: the anomalous acquisition of information about distant physical
      targets. Remarkably, neither of these extraordinary capabilities shows any
      dependence on either the distance or the time separating the participant from the
      target. The relevance of these consciousness abilities to human health follows
      from recognition that physiology entails myriad subtle information processes, all
      of which involve some degree of randomicity in their normal functions, and thus
      may be similarly influenced by conscious volition.

PMID- 17560345
TI  - Consciousness, information, and living systems.
AB  - The possibility of a proactive role for consciousness in the establishment of
      physical reality has been addressed via an extensive 26-year program
      investigating physical anomalies in human/machine interactions and non-sensory
      acquisition of information about remote geographical locations. Empirical
      databases comprising many hundreds of millions of random events confirm that
      information can be introduced into, or extracted from, otherwise random physical
      processes solely through the agencies of human intention and subjective
      resonance. Much of the evidence mitigates the likelihood that the anomalies are
      manifestations of neo-cortical cognitive activity. Rather, they may be
      expressions of a deeper information organizing capacity of biological origin that
      emerges from the uncertainty inherent in the complexity of all living systems.

PMID- 17560346
TI  - Correlations of random binary sequences with pre-stated operator intention: a
      review of a 12-year program.
AB  - Strong correlations between output distribution means of a variety of random
      binary processes and pre-stated intentions of some 100 individual human operators
      have been established over a 12-year experimental program. More than 1000
      experimental series, employing four different categories of random devices and
      several distinctive protocols, show comparable magnitudes of anomalous mean
      shifts from chance expectation, with similar distribution structures. Although
      the absolute effect sizes are quite small, of the order of 10(-4) bits deviation
      per bit processed, over the huge databases accumulated, the composite effect
      exceeds 7sigma (p approximately 3.5 x 10(-13)). These data display significant
      disparities between female and male operator performances, and consistent serial
      position effects in individual and collective results. Data generated by
      operators far removed from the machines and exerting their efforts at times other
      than those of machine operation show similar effect sizes and structural details
      to those of the local, on-time experiments. Most other secondary parameters
      tested are found to have little effect on the scale and character of the results,
      with one important exception: studies performed using fully deterministic
      pseudorandom sources, either hard-wired or algorithmic, yield null overall mean
      shifts, and display no other anomalous features.

PMID- 17560347
TI  - Information and uncertainty in remote perception research.
AB  - This article has four purposes: 1) to present for the first time in archival form
      all results of some 25 years of remote perception research at this laboratory; 2)
      to describe all of the analytical scoring methods developed over the course of
      this program to quantify the amount of anomalous information acquired in the
      experiments; 3) to display a remarkable anti-correlation between the objective
      specificity of those methods and the anomalous yield of the experiments; and 4)
      to discuss the phenomenological and pragmatic implications of this
      complementarity. The formal database comprises 653 experimental trials performed
      over several phases of investigation. The scoring methods involve various arrays
      of descriptor queries that can be addressed to both the physical targets and the
      percipients' description thereof, the responses to which provide the basis for
      numerical evaluation and statistical assessment of the degree of anomalous
      information acquired. Twenty-four such recipes have been employed, with queries
      posed in binary, ternary, quaternary, and ten-level distributive formats. Thus
      treated, the database yields a composite z-score against chance of 5.418 (p = 3 x
      10(-8), one-tailed). Numerous subsidiary analyses agree that these overall
      results are not significantly affected by any of the secondary protocol
      parameters tested, or by variations in descriptor effectiveness, possible
      participant response biases, target distance from the percipient, or time
      interval between perception effort and agent target visitation. However, over the
      course of the program there has been a striking diminution of the anomalous yield
      that appears to be associated with the participants' growing attention to, and
      dependence upon, the progressively more detailed descriptor formats and with the
      corresponding reduction in the content of the accompanying free-response
      transcripts. The possibility that increased emphasis on objective quantification
      of the phenomenon somehow may have inhibited its inherently subjective expression
      is explored in several contexts, ranging from contemporary signal processing
      technologies to ancient divination traditions. An intrinsic complementarity is
      suggested between the analytical and intuitive aspects of the remote perception
      process that, like its more familiar counterpart in quantum science, brings with
      it an inescapable uncertainty that limits the extent to which such anomalous
      effects can be simultaneously produced and evaluated.

PMID- 17560356
TI  - FieldREG II: consciousness field effects: replications and explorations.
AB  - Based on formal analysis of 18 exploratory applications, 12 of which have been
      reported previously, a testable general hypothesis for FieldREG experiments has
      been postulated, namely that data taken in environments fostering relatively
      intense or profound subjective resonance will show larger deviations of the mean
      relative to chance expectation than those generated in more pragmatic assemblies.
      The 61 subsequent FieldREG applications reported here comprise 21 hypothesis
      based formal replications, along with 40 further explorations designed to learn
      more about the circumstances that favor anomalous deviations. The results of the
      formal replications strongly confirm the general hypothesis, yielding a composite
      probability against chance for the resonant subset of 2.2 x 10(-6) compared to
      0.91 for the mundane subset. The exploratory work suggests other venues in which
      anomalous effects of group consciousness can be expected, and also identifies a
      number of situations that do not appear to be conducive to such responses.

PMID- 17560358
TI  - Science of the subjective.
AB  - Over the greater portion of its long scholarly history, the particular form of
      human observation, reasoning, and technical deployment we properly term "science"
      has relied at least as much on subjective experience and inspiration as it has on
      objective experiments and theories. Only over the past few centuries has
      subjectivity been progressively excluded from the practice of science, leaving an
      essentially secular analytical paradigm. Quite recently, however, a compounding
      constellation of newly inexplicable physical evidence, coupled with a growing
      scholarly interest in the nature and capability of human consciousness, are
      beginning to suggest that this sterilization of science may have been excessive
      and could ultimately limit its epistemological reach and cultural relevance. In
      particular, an array of demonstrable consciousness-related anomalous physical
      phenomena, a persistent pattern of biological and medical anomalies, systematic
      studies of mind/brain relationships and the mechanics of human creativity, and a
      burgeoning catalogue of human factors effects within contemporary information
      processing technologies, all display empirical correlations with subjective
      aspects that greatly complicate, and in many cases preclude, their comprehension
      on strictly objective grounds. However, any disciplined re-admission of
      subjective elements into rigorous scientific methodology will hinge on the
      precision with which they can be defined, measured, and represented, and on the
      resilience of established scientific techniques to their inclusion. For example,
      any neo-subjective science, while retaining the logical rigor,
      empirical/theoretical dialogue, and cultural purpose of its rigidly objective
      predecessor, would have the following requirements: acknowledgment of a proactive
      role for human consciousness; more explicit and profound use of interdisciplinary
      metaphors; more generous interpretations of measurability, replicability, and
      resonance; a reduction of ontological aspirations; and an overarching
      teleological causality. Most importantly, the subjective and objective aspects of
      this holistic science would have to stand in mutually respectful and constructive
      complementarity to one another if the composite discipline were to fulfill itself
      and its role in society.

PMID- 17560360
TI  - The complementarity of consciousness.
AB  - The concept of complementarity, originally proposed by Bohr in a microphysical
      context, and subsequently extended by himself, Heisenberg and Pauli to encompass
      subjective as well as objective dimensions of human experience, can be further
      expanded to apply to many common attitudes of human consciousness. At issue is
      the replacement of strict polar opposition of superficially antithetical
      consciousness capacities, such as analysis and synthesis, logic and intuition, or
      doing and being, by more generous conjugation that allows the pairs to operate in
      constructive triangulation and harmony. In this format, the physical principle of
      uncertainty also acquires metaphoric relevance in limiting the attainable
      sharpness of specification of any consciousness complements, and may serve to
      define their optimum balance in establishing reality. These principles thus lend
      themselves to representation of wave-like vs. particle-like operations of
      consciousness; to trade-offs between rigor and ambience in consciousness
      research; to generic masculine/feminine reinforcement; and to the interplay of
      science and spirit in any creative enterprise.

PMID- 17560361
TI  - A modular model of mind/matter manifestations (M5).
AB  - While ongoing empirical research into anomalous mind/matter interactions
      continues to reaffirm the reality of such phenomena, it has heretofore failed to
      stimulate viable theoretical models, or even to suggest effective strategies for
      more productive experimentation. In contrast to prevalent presumption, re
      examination of several large databases from this laboratory raises doubt that
      such effects are produced by direct attention of the conscious mind to the
      observable physical processes addressed. Rather, an alternative route is
      indicated wherein unconscious mind and intangible physical mechanisms are invoked
      to achieve anomalous acquisition of mental information about, or anomalous mental
      influence upon, otherwise inaccessible material processes. Implications for more
      effective experiments include subtler feedback schemes that facilitate submission
      of conscious intention to unconscious mental processing; physical target systems
      that provide a richness of intangible potentialities; operators who are amenable
      to such interactions; and an environmental ambience that supports the composite
      strategy. Theoretical requisites include better understanding of the information
      dialogue between conscious and unconscious aspects of mind; more pragmatic
      formulations of the relations between tangible and intangible physical processes;
      and most importantly, cogent representation of the merging of mental and material
      dimensions into indistinguishability at their deepest levels.

PMID- 17560363
TI  - Sensors, filters, and the source of reality.
AB  - The failure of contemporary scientific theory to correlate and explicate
      anomalous consciousness-related physical phenomena may trace to inadequate
      comprehension of the process of information exchange between the mind and its
      ultimate source. Elevation of the subjective capacities of consciousness to
      complementary status with the more objective physical senses, along with
      recognition of the bi-directional capabilities of both categories, allows
      establishment of resonant channels of communication between the mind and its
      source environment that can exceed conventional expectations. In this manner,
      order can be introduced into randomnicity, and self-consistent realities can be
      extracted from transcendent chaos. The key elements in tuning these channels to
      amplify such information creation are the physiological and psychological filters
      imposed upon them, some of which can be enhanced or altered by conscious or
      unconscious attention. Specifically, such attitudinal tactics as openness to
      alternative perspectives, utilization of transdisciplinary metaphors, self
      sacrificial resonance, tolerance of uncertainty, and replacement of dualistic
      rigor by mental complementarity can enable experiential realities that are
      responsive to intention, desire, or need, to an extent consistent with prevailing
      empirical evidence.

PMID- 17560364
TI  - Endophysical models based on empirical data.
AB  - Any proposed endophysical models need to acknowledge a number of subjective
      correlates that have been well established in such objectively quantifiable
      experimental contexts as anomalous human/machine interactions and remote
      perception information acquisition. Most notable of these factors are conscious
      and unconscious intention; gender disparities; serial position effects; intrinsic
      uncertainties; elusive replicability; and emotional resonance between the
      participants and the devices, process, and tasks. Perhaps even more pertinent are
      the insensitivities of the anomalous effects to spatial and temporal separations
      of the participants form the physical targets. Inclusion of subjective
      coordinates in the models, and exclusion of physical distance and time, raise
      formidable issues of specification, quantification, and dynamical formulation
      from both the physical and psychological perspectives. A few primitive examples
      of possible approaches are presented.

PMID- 17560365
TI  - The pertinence of the Princeton Engineering Anomalies (PEAR) Laboratory to the
      pursuit of global health. Epilogue.

PMID- 17560367
TI  - The coming of age for Piwi proteins.
AB  - Piwi proteins, a subfamily of Argonaute (Ago) proteins, have recently been shown
      to bind endogenous small RNAs. However, differences between Ago proteins (which
      bind microRNAs and small interfering RNAs) and Piwi proteins and Piwi-interacting
      RNAs (piRNAs) suggest novel functions for Piwi proteins. Here, we highlight the
      recent progress in understanding Piwi function and the implications for germline
      and stem cell development.

PMID- 17560368
TI  - Argonaute proteins: mediators of RNA silencing.
AB  - Small regulatory RNAs such as short interfering RNAs (siRNAs), microRNAs
      (miRNAs), and Piwi interacting RNAs (piRNAs) have been discovered in the past,
      and it is becoming more and more apparent that these small molecules have key
      regulatory functions. Small RNAs are found in all higher eukaryotes and play
      important roles in cellular processes as diverse as development, stress response,
      or transposon silencing. Soon after the discovery of small regulatory RNAs,
      members of the Argonaute protein family were identified as their major cellular
      protein interactors. This review focuses on the various cellular functions of
      mammalian Argonaute proteins in conjunction with the different small RNA species
      that are known today.

PMID- 17560369
TI  - Evidence for an adaptation mechanism of mitochondrial translation via tRNA import
      from the cytosol.
AB  - Although mitochondrial import of nuclear DNA-encoded RNAs is widely occurring,
      their functions in the organelles are not always understood. Mitochondrial
      function(s) of tRNA(Lys)(CUU), tRK1, targeted into Saccharomyces cerevisiae
      mitochondria was mysterious, since mitochondrial DNA-encoded tRNA(Lys)(UUU),
      tRK3, was hypothesized to decode both lysine codons, AAA and AAG. Mitochondrial
      targeting of tRK1 depends on the precursor of mitochondrial lysyl-tRNA
      synthetase, pre-Msk1p. Here we show that substitution of pre-Msk1p by its Ashbya
      gossypii ortholog results in a strain in which tRK3 is aminoacylated, while tRK1
      is not imported. At elevated temperature, drop of tRK1 import inhibits
      mitochondrial translation of mRNAs containing AAG codons, which coincides with
      the impaired 2-thiolation of tRK3 anticodon wobble nucleotide. Restoration of
      tRK1 import cures the translational defect, suggesting the role of tRK1 in
      conditional adaptation of mitochondrial protein synthesis. In contrast with the
      known ways of organellar translation control, this mechanism exploits the RNA
      import pathway.

PMID- 17560370
TI  - A peptide signal for adapter protein-mediated degradation by the AAA+ protease
      ClpCP.
AB  - ComS is an antiadaptor protein that binds to MecA, displacing the competence
      transcription factor ComK. This protects ComK from degradation by the ClpCP
      protease and turns on the switch leading to bistable gene expression. Here we
      identify the motifs on ComK and ComS that mediate binding to MecA, and we show
      that they contain similar core sequences (FMLYPK and IILYPR, respectively),
      located near the C and N termini of the respective proteins. A 17 residue peptide
      from ComK including this sequence has the same affinity for MecA as full-length
      ComK, and a peptide containing this sequence is sufficient to target green
      fluorescent protein for degradation in vivo. Crosslinking and competition
      experiments demonstrate that ComK- and ComS-derived peptides bind to the same
      region of MecA. We propose a model in which the antiadaptor protein ComS acts by
      direct competition to protect ComK from degradation.

PMID- 17560371
TI  - Cyclin Cln3 is retained at the ER and released by the J chaperone Ydj1 in late G1
      to trigger cell cycle entry.
AB  - G1 cyclin Cln3 plays a key role in linking cell growth and proliferation in
      budding yeast. It is generally assumed that Cln3, which is present throughout G1,
      accumulates passively in the nucleus until a threshold is reached to trigger cell
      cycle entry. We show here that Cln3 is retained bound to the ER in early G1
      cells. ER retention requires binding of Cln3 to the cyclin-dependent kinase
      Cdc28, a fraction of which also associates to the ER. Cln3 contains a chaperone
      regulatory Ji domain that counteracts Ydj1, a J chaperone essential for ER
      release and nuclear accumulation of Cln3 in late G1. Finally, Ydj1 is limiting
      for release of Cln3 and timely entry into the cell cycle. As protein synthesis
      and ribosome assembly rates compromise chaperone availability, we hypothesize
      that Ydj1 transmits growth capacity information to the cell cycle for setting
      efficient size/ploidy ratios.

PMID- 17560372
TI  - Sch9 is a major target of TORC1 in Saccharomyces cerevisiae.
AB  - The Target of Rapamycin (TOR) protein is a Ser/Thr kinase that functions in two
      distinct multiprotein complexes: TORC1 and TORC2. These conserved complexes
      regulate many different aspects of cell growth in response to intracellular and
      extracellular cues. Here we report that the AGC kinase Sch9 is a substrate of
      yeast TORC1. Six amino acids in the C terminus of Sch9 are directly
      phosphorylated by TORC1. Phosphorylation of these residues is lost upon rapamycin
      treatment as well as carbon or nitrogen starvation and transiently reduced
      following application of osmotic, oxidative, or thermal stress. TORC1-dependent
      phosphorylation is required for Sch9 activity, and replacement of residues
      phosphorylated by TORC1 with Asp/Glu renders Sch9 activity TORC1 independent.
      Sch9 is required for TORC1 to properly regulate ribosome biogenesis, translation
      initiation, and entry into G0 phase, but not expression of Gln3-dependent genes.
      Our results suggest that Sch9 functions analogously to the mammalian TORC1
      substrate S6K1 rather than the mTORC2 substrate PKB/Akt.

PMID- 17560373
TI  - TNF-induced activation of the Nox1 NADPH oxidase and its role in the induction of
      necrotic cell death.
AB  - Tumor necrosis factor (TNF) is an important cytokine in immunity and inflammation
      and induces many cellular responses, including apoptosis and necrosis. TNF
      signaling enables the generation of superoxide in phagocytic and vascular cells
      through the activation of the NADPH oxidase Nox2/gp91. Here we show that TNF also
      activates the Nox1 NADPH oxidase in mouse fibroblasts when cells undergo
      necrosis. TNF treatment induces the formation of a signaling complex containing
      TRADD, RIP1, Nox1, and the small GTPase Rac1. TNF-treated RIP1-deficient
      fibroblasts fail to form such a complex, indicating that RIP1 is essential for
      Nox1 recruitment. Moreover, the prevention of TNF-induced superoxide generation
      with dominant-negative mutants of TRADD or Rac1, as well as knockdown of Nox1
      using siRNA, inhibits necrosis. Thus our study suggests that activation of Nox1
      through forming a complex with TNF signaling components plays a key role in TNF
      induced necrotic cell death.

PMID- 17560374
TI  - XIAP induces NF-kappaB activation via the BIR1/TAB1 interaction and BIR1
      dimerization.
AB  - In addition to caspase inhibition, X-linked inhibitor of apoptosis (XIAP) induces
      NF-kappaB and MAP kinase activation during TGF-b and BMP receptor signaling and
      upon overexpression. Here we show that the BIR1 domain of XIAP, which has no
      previously ascribed function, directly interacts with TAB1 to induce NF-kappaB
      activation. TAB1 is an upstream adaptor for the activation of the kinase TAK1,
      which in turn couples to the NF-kappaB pathway. We report the crystal structures
      of BIR1, TAB1, and the BIR1/TAB1 complex. The BIR1/TAB1 structure reveals a
      striking butterfly-shaped dimer and the detailed interaction between BIR1 and
      TAB1. Structure-based mutagenesis and knockdown of TAB1 show unambiguously that
      the BIR1/TAB1 interaction is crucial for XIAP-induced TAK1 and NF-kappaB
      activation. We show that although not interacting with BIR1, Smac, the antagonist
      for caspase inhibition by XIAP, also inhibits the XIAP/TAB1 interaction.
      Disruption of BIR1 dimerization abolishes XIAP-mediated NF-kappaB activation,
      implicating a proximity-induced mechanism for TAK1 activation.

PMID- 17560375
TI  - Structure of IRF-3 bound to the PRDIII-I regulatory element of the human
      interferon-beta enhancer.
AB  - Interferon regulatory factor 3 (IRF-3) is a key transcription factor in the
      assembly of the mammalian interferon-beta (IFN-beta) enhanceosome. We present
      here the structure of IRF-3 DNA binding domain in complex with the complete
      PRDIII-I regulatory element of the human IFN-beta enhancer. We show that four IRF
      3 molecules bind in tandem to, variably spaced, consensus and nonconsensus IRF
      sites on the composite element. The ability of IRF-3 to bind these variable sites
      derives in part from two nonconserved arginines (Arg78 and Arg86) that partake in
      alternate protein-DNA contacts. We also show that the protein-DNA contacts are
      highly overlapped and that all four IRF sites are required for gene activation in
      vivo. In addition, we show that changing the nonconsensus IRF sites to consensus
      sites creates a more efficient enhancer in vivo. Together, the structure and
      accompanying biological data provide insights into the assembly of the IFN-beta
      enhanceosome in mammals.

PMID- 17560376
TI  - Purification of a plant mediator from Arabidopsis thaliana identifies PFT1 as the
      Med25 subunit.
AB  - Mediator, a central coregulator of transcription, has been identified as a large
      protein complex in eukaryotes ranging from yeast to man. It is therefore
      remarkable that Mediator has not yet been identified within the plant kingdom.
      Here we identify Mediator in a plant, Arabidopsis thaliana. The plant Mediator
      subunits typically show very low homology to other species, but our biochemical
      purification identifies 21 conserved and six A. thaliana-specific Mediator
      subunits. Most notably, we identify the A. thaliana proteins STRUWWELPETER (SWP)
      and PHYTOCHROME AND FLOWERING TIME 1 (PFT1) as the Med14 and Med25 subunits,
      respectively. These findings show that specific plant Mediator subunits are
      linked to the regulation of specialized processes such as the control of cell
      proliferation and the regulation of flowering time in response to light quality.
      The identification of the plant Mediator will provide new tools and insights into
      the regulation of transcription in plants.

PMID- 17560378
TI  - Amperometric biosensor based on Prussian Blue-modified screen-printed electrode
      for lipase activity and triacylglycerol determination.
AB  - Lipase activity against triacylglycerols has been measured using an amperometric
      enzyme biosensor based on glycerol dehydrogenase/NADH oxidase. A Prussian Blue
      modified screen-printed electrode was selected as substrate for the two
      immobilised-enzyme systems due to their higher operative stability reported in
      previous works. Various parameters such as cofactor (flavin mononucleotide FMN)
      concentration (1 mM), NAD+ coenzyme concentration (2 mM), pH effect (phosphate
      buffer pH 6 to 8, Tris buffer pH 8-10) response time and storage stability were
      evaluated and optimised. The glycerol biosensor was then investigated for lipase
      activity. The system was challenged against an olive or sunflower oil real
      samples in order to detect fatty acids and the results were compared with those
      provided either by the manufacture or reference methods with good agreement.

PMID- 17560377
TI  - MicroRNA-mediated feedback and feedforward loops are recurrent network motifs in
      mammals.
AB  - MicroRNAs (miRNAs) are regulatory molecules that participate in diverse
      biological processes in animals and plants. While thousands of mammalian genes
      are potentially targeted by miRNAs, the functions of miRNAs in the context of
      gene networks are not well understood. Specifically, it is unknown whether miRNA
      containing networks have recurrent circuit motifs, as has been observed in
      regulatory networks of bacteria and yeast. Here we develop a computational method
      that utilizes gene expression data to show that two classes of circuits
      corresponding to positive and negative transcriptional coregulation of a miRNA
      and its targets-are prevalent in the human and mouse genomes. Additionally, we
      find that neuronal-enriched miRNAs tend to be coexpressed with their target
      genes, suggesting that these miRNAs could be involved in neuronal homeostasis.
      Our results strongly suggest that coordinated transcriptional and miRNA-mediated
      regulation is a recurrent motif to enhance the robustness of gene regulation in
      mammalian genomes.

PMID- 17560379
TI  - Polychlorinated biphenyls (PCBs) detection in milk samples by an electrochemical
      magneto-immunosensor (EMI) coupled to solid-phase extraction (SPE) and disposable
      low-density arrays.
AB  - An electrochemical immunosensor for polychlorinated biphenyl (PCB) detection
      based on graphite screen-printed low-density arrays and on magnetic beads is
      reported. The immunological reaction for the detection of PCBs is based on a
      direct competitive assay using alkaline phosphatase (AP) as enzymatic label.
      After the immunochemical recognition, the modified magnetic beads are captured by
      a magnet on the surface of the graphite working electrode. The electrochemical
      detection is thus achieved through the addition of the AP substrate (alpha
      naphthyl-phosphate). Two different antibodies (sIgG anti-PCB28 and rIgG anti
      PCB77) were tested and compared in terms of sensitivity and ability to recognise
      different congeners. The developed electrochemical magneto-immunosensor (EMI) was
      successfully combined with solid-phase extraction (SPE) for the analysis of PCBs
      in milk samples. In spiked samples a recovery of 80% was obtained. The proposed
      strategy offers great promise for rapid, simple, cost-effective, and on-site
      analysis of clinical, food and environmental samples, considering also that low
      density arrays allow the simultaneous analysis of different processed samples.

PMID- 17560380
TI  - Improved performance of polyaniline-uricase biosensor.
AB  - Uricase has been covalently immobilized using glutaraldehyde as cross-linker onto
      electrochemically synthesized polyaniline (PANI) films. These PANI-uricase
      electrodes have been characterized using spectroscopic, cyclic voltammetry and
      impedance measurements. The morphology and covalent linkage of uricase lead to
      high enzyme loading and better shelf life. The value of the Michaelis-Menton
      constant obtained as 5.1x10(-3) mM L(-1) for the immobilized uricase compared to
      3.4x10(-1) mM L(-1) for the free uricase enzyme, suggests enhancement in affinity
      and/or activity of uricase attached to PANI. The influence of pH, temperature and
      concentration on electrode activity were studied. The enzyme electrodes were
      found to retain 95% of activity after 17-18 weeks when stored at 4 degrees C.
      These electrodes have a response time of about 60 s and have been used to measure
      uric acid concentration in serum. These PANI-uricase electrodes can be used for
      about 30 times for electrochemical measurements while retaining about 90% of its
      activity indicating improved performance.

PMID- 17560381
TI  - Nanomolar detection of hydrogen peroxide on glassy carbon electrode modified with
      electrodeposited cobalt oxide nanoparticles.
AB  - The electrochemical detection of H2O2 was investigated on a cobalt oxide
      nanoparticles modified glassy carbon electrode in phosphate buffer solution (pH
      7). Cyclic voltammetry at potential range -1.1 to 1.1 V from CoCl2 natural
      aqueous solution produced well defined cobalt oxide nanoparticles deposited on
      the surface of glassy carbon electrode. The surface of resulting electrode was
      characterized with SEM. The formation of cobalt oxyhydroxide film was
      investigated by cyclic voltammetry in alkaline and natural aqueous solution. The
      modified electrode showed well defined and stable redox couples in both alkaline
      and natural aqueous solution. The modified electrode showed excellent
      electrocatalytic activity for oxidation of hydrogen peroxide. The response to
      H2O2 on the modified electrode was examined using cyclic voltammetry and
      amperometry. The amperometric detection of hydrogen peroxide is carried out at
      0.75 V versus Ag/AgCl reference electrode in phosphate buffer solution with pH
      7.4. The detection limit (S/N=3) was 0.4 nM with linearity up to 6 orders of
      magnitude and sensitivity of 4.86 microA microM(-1) cm(-2). The response time of
      the electrode to achieve 95% of the steady-state current is <2 s. No measurable
      reduction in analytical performance of the modified electrode was found by
      storing the electrode in ambient conditions for 20 days. This modified electrode
      recedes many advantages such as remarkable catalytic activity, good
      reproducibility, simple preparation procedure and long term stability of signal
      response during hydrogen peroxide oxidation. The immobilization of cobalt oxide
      nanoparticles on the surface of GC electrode appears to be a highly efficient
      method for the development of a new class of sensitive, stable and reproducible
      hydrogen peroxide electrochemical sensor.

PMID- 17560382
TI  - Redox potential of tea infusion as an index for the degree of fermentation.
AB  - Redox potential of tea infusion is suggested as an index for the extent of tea
      fermentation. The potential was measured between platinum and Ag/AgCl electrode
      pair with a voltmeter with high input impedance (>1000 Gohms). Phosphate buffer
      (10 mM, pH 7.0) was used to extract the infusion and served as the supporting
      electrolytes for the electrochemical measurement. The reliability (the Nernst's
      behavior) for redox potential measurement was verified with a standard redox
      couple, ferricyanide/ferrocyanide. Tentative interferences from dissolved oxygen
      and the major coexisting reducing chemical, ascorbate, were discussed. Redox
      potential showed strong correlation with the fermentation process during indoor
      withering process. Eleven kinds of tea with different fermentation extents
      including Sencha, Pilochun, Pouchong, Formosa oolong tea, Lipton green tea,
      Lipton black tea, and Taiwanese black tea were tested.

PMID- 17560383
TI  - Cholinesterase-based dipstick assay for the detection of organophosphate and
      carbamate pesticides.
AB  - A cholinesterase (ChE)-based dipstick-type assay for the class-specific detection
      of organophosphate (OP) and carbamate (CM) pesticides was developed. The
      principle of the assay is based on inhibition of the activity of a ChE by these
      two families of pesticides, which is dependent on the concentration of
      pesticides. The proposed assay system is composed of a test strip with an
      acetylcholinesterase (AChE)-coated membrane and an enzyme substrate solution. The
      assay protocol involves incubation of the enzyme-coated strip in the pesticide
      containing sample solution followed by incubation of the sample-treated strip in
      a chromogenic enzyme substrate solution. The color intensity is estimated by the
      naked eye or a reflectometer. Of the membranes tested as the enzyme support,
      Hybond N+ was the most suitable. Among the compounds tested as the enzyme
      substrate, indophenyl acetate was the best. The detectable concentration range of
      the dipstick assay for the OP and CM pesticides was 10(-6)-10(2) and 10(-6)-10(0)
      microg mL(-1), respectively. The sensitivity of the dipstick assay to the
      oxidized form of parathion (paraoxon) was higher than to parathion. The strip
      showed a large matrix effect with pesticide-spiked lettuce samples, whereas it
      showed a small matrix effect with pesticide-spiked rice samples.

PMID- 17560384
TI  - Voltammetric characterization of metal sulfide particles and nanoparticles in
      model solutions and natural waters.
AB  - Voltammetric scans in sulfidic natural waters often reveal reduction peaks in the
      range -0.9 to -1.35 V versus Ag/AgCl. These peaks have been attributed to iron
      sulfide complexes or clusters. However, sols containing CuS nanoparticles now
      also are known to produce reduction peaks in this range. Here we investigate the
      voltammetric behavior of two additional metal sulfides at the Hg electrode in
      0.55 M NaCl + 0.03 M NaHCO3 electrolyte, pH=8.5. We show that Pb and Hg sulfides,
      either as suspended powders or as precipitated nanoparticles, also yield cathodic
      peaks between -0.9 and -1.35 V, similar to peaks obtained with CuS and FeS. For
      precipitated nanoparticles, the position and shape of these reduction peaks
      change with ageing. Freshly formed nanoparticles produce less negative reduction
      peaks than aged nanoparticles. Peaks from aged nanoparticles often consist of two
      or more superimposed reduction peaks. When all other experimental parameters are
      held constant, the amount of nanoparticle analyte accumulated on the electrode
      increases with the amount of ageing (< or = 1 h). Addition of EDTA or
      acidification followed by purging can be used to distinguish PbS nanoparticles
      and Fe sulfide clusters from CuS and HgS nanoparticles or from colloidal S. This
      test was applied to interpret -0.9 to -1.35 V reduction peaks observed in two
      meromictic lakes. In conjunction with other evidence, this test suggests that FeS
      clusters are present in one case whereas colloidal S is present in the other.
      Interpreting -0.9 to -1.35 V voltammetric peaks observed in sulfidic natural
      waters requires caution, but these peaks are potentially rich sources of
      information about trace metal speciation.

PMID- 17560385
TI  - Simultaneous determination of suspended particulate trace metals (Co, Ni, Cu, Zn,
      Cd and Pb) in seawater with small volume filtration assisted by microwave
      digestion and flow injection inductively coupled plasma mass spectrometer.
AB  - A new technique for the determination of suspended particulate trace metals (P
      metals >0.2 microm), such as Co, Ni, Cu, Zn, Cd and Pb, in open ocean seawater
      has been developed by using microwave digestion coupled with flow injection
      inductively coupled plasma mass spectrometry (FI-ICP-MS). Suspended particulate
      matter (SPM) was collected from 500 mL of seawater on a Nuclepore filter (0.2
      microm) using a closed filtration system. Both the SPM and filter were completely
      dissolved by microwave digestion. Reagents for the digestion were evaporated
      using a clean evaporation system, and the metals were redissolved in 0.8 M HNO3.
      The solution was diluted with buffer solution to give pH 5.0 and the metals were
      determined by FI-ICP-MS using a chelating adsorbent of 8-hydroxyquinoline
      immobilized on fluorinated metal alkoxide glass (MAF-8HQ). The procedure blanks
      with a filter were found to be 0.048+/-0.008, 10.3+/-0.3, 0.27+/-0.05, 3.3+/-1.8,
      0.02+/-0.03 and 0.85+/-0.09 ng L(-1) for Co, Ni, Cu, Zn, Cd and Pb, respectively
      (n=14). Detection limits defined as 3 times the standard deviation of the blanks
      were 0.023, 0.90, 0.14, 5.3, 0.078 and 0.28 ng L(-1) for Co, Ni, Cu, Zn, Cd and
      Pb, respectively. Accuracy was evaluated using certified reference materials of
      chlorella (NES CRM No. 3) and marine sediment (HISS-1). The method was applied to
      the determination of vertical distributions for P-Co, Ni, Cu, Zn, Cd and Pb in
      the Western North Pacific.

PMID- 17560386
TI  - Determination of trace rare earth elements in environmental samples by low
      temperature electrothermal vaporization inductively coupled plasma mass
      spectrometry after synergistic extraction with dimethylheptyl methyl phosphate
      and 1-phenyl-3-methyl-4-benzoyl-pyrazalone-5.
AB  - Synergistic extraction of trace rare earth elements (REEs) from nitrate solutions
      using mixtures of dimethylheptyl methyl phosphate (P350) and 1-phenyl-3-methyl-4
      benzoyl-pyrazalone-5 (PMBP) in hexamethylene has been investigated. The factors
      affecting the synergistic extraction of rare earth ions, such as pH, organic
      solvent and phase ratio of organic phase to aqueous phase were systematically
      studied. The synergistic enhancement factors of P350 and PMBP for REEs were
      calculated to be 4.3-5.8. After the synergistic extraction, the postextraction
      organic phase was directly introduced into the graphite furnace for
      electrothermal vaporization inductively coupled plasma mass spectrometry (ETV-ICP
      MS) determination. It was found that PMBP along with P350 has an obvious chemical
      modification for REEs, and the limits of detection (LODs) for 15 REEs were in the
      range of 0.02-0.09 ng L(-1). The proposed method was found to be more suitable
      for the analysis of environmental samples with complex matrix.

PMID- 17560387
TI  - Flow-injection interface for on-line coupling solid-phase extraction and X-ray
      fluorescence measurements.
AB  - A flow-injection (FI) manifold including a solid-phase extraction (SPE) mini
      column has been coupled on-line to an energy-dispersive X-ray fluorescence
      detector (EDXRFD) by locating a lab-modified 18-microL flow-cell, 10-mm path
      length, connected to the SPE column by PTFE tubing of 0.5 mm i.d., in the X-ray
      spectrometer chamber. The optical window of the flow-cell was adjusted and fixed
      to the X-ray irradiation zone of the spectrometer. Two PTFE tubes connected the
      flow-cell to the FI device and were introduced into the spectrometer chamber by a
      small orifice without distortion nor modification of the instrument. The SPE
      EDXRFD coupling was tested for Pb and Cd aqueous solutions using Dowex 50 cation
      exchange resin as sorbent, and flushing the eluate through the flow-cell for
      monitoring. The LODs and LOQs thus obtained were 1 and 3.2 microg for Pb and 1.8
      and 4.8 microg for Cd, respectively; values which allow using the approach for
      the analysis of waste water by injecting 20 mL of sample into the FI manifold.
      The linear dynamic ranges are a function of the sample volume circulated through
      the mini-column. For a sample volume of 20 mL the ranges are between 1 and 4000
      microg for Pb and between 1.8 and 2000 microg for Cd. The method was validated by
      the standard addition method using ground-water samples. The SPE-EDXRFD coupling
      enables to carry out the study of those variables influencing the SPE process-
      namely, the effect of the sample volume flushed through the column, concentration
      of analytes in the sample, amount of resin packed, breakthrough volume of the
      resin, elution profiles, sample pH and retention and elution flow-rates--in an
      automatic, cheap, fast and precise way.

PMID- 17560388
TI  - Solvent exchange using hollow fiber prior to separation and determination of some
      antioxidants by high performance liquid chromatography.
AB  - This study presents a simple and rapid solvent exchange procedure using a hollow
      fiber. Antioxidants (Irganox 1010, Irganox 1076 and Irgafos 168) and solvents
      such as tetrahydrofuran (THF), carbon tetrachloride and toluene were selected as
      model compounds and sample solvents, respectively. After injection of the sample
      solution into the hollow fiber and solvent evaporation, the precipitated analytes
      in lumen and pores of the fiber were washed with methanol (the mobile phase for
      separation and determination by HPLC-diode array detection) and good
      chromatographic peaks were obtained. The effect of different parameters such as
      fiber length, volumes of sample and washing solvents were investigated and the
      optimum conditions were selected. The repeatability of the method was tested and
      it was found that the relative standard deviation (R.S.D.) was less than 10% for
      all analytes. Also enrichment factors of 3.03, 2.21 and 1.19 times were obtained
      for Irganox 1010, Irganox 1076 and Irgafos 168, respectively, when 200 microL
      sample and 50 microL methanol (washing solvent) were used.

PMID- 17560389
TI  - Evaluation of carbon nanotubes as a solid-phase extraction adsorbent for the
      extraction of cephalosporins antibiotics, sulfonamides and phenolic compounds
      from aqueous solution.
AB  - The adsorptive potential of carbon nanotubes (single-walled carbon nanotubes and
      multi-walled carbon nanotubes) for solid-phase extraction of three groups of
      highly polar compounds (namely cephalosporins antibiotics, sulfonamides and
      phenolic compounds) was tested in this article. The analytes were strongly
      retained by the carbon nanotubes. And acceptable recoveries were obtained with
      the addition of ammonium acetate into eluents. The effects of solution pH on the
      recoveries of the antibiotics and phenolic compounds were examined. To check the
      retention abilities of three groups of compounds on carbon nanotubes, fixed
      amount of each analyte was added to different volumes (up to 500 mL) of aqueous
      solution, and then extracted by the sorbents. Comparative studies showed that the
      carbon nanotubes were much superior to C18 for the extraction of the highly polar
      analytes. For the cephalosporins antibiotics and sulfonamides, the carbon
      nanotubes showed stronger retention capability than graphitized carbon blacks,
      but for some of the phenolic compounds graphitized carbon blacks seemed to be
      more suitable, indicating different retention mechanisms of these analytes. To
      further assess the enrichment ability of carbon nanotubes for highly polar
      compounds, the solid-phase extraction method of multi-walled carbon nanotubes
      packed cartridge was well developed, and the sulfonamides were used as model
      compounds. Under the optimal procedures, the detection limits of sulfonamides
      were in the range of 27-38 ng L(-1). The spiked recoveries from several real
      water samples obtained for sulfathiazole and sulfadiazine ranged from 55% to 79%
      and 72% to 92%, respectively, while the recoveries of sulfapyridine and
      sulfamethazine were in the range of 85-102%.

PMID- 17560390
TI  - Homogeneous liquid-liquid extraction of trace amounts of mononitrotoluenes from
      waste water samples.
AB  - Homogeneous liquid-liquid extraction method was studied based on a phase
      separation phenomenon in a ternary solvent system. According to this procedure,
      mononitrotoloenes were extracted by single-phase extraction in a
      water/methanol/chloroform, homogeneous ternary solvent system. Methanol and
      chloroform were used as consolute and extraction solvents, respectively. The
      homogeneous solution was broken by the addition of salt and a cloudy solution was
      formed. After centrifugation, the fine droplets of the extraction solvent were
      sedimented in the bottom of the conical test tube. Analysis of the extracts was
      carried out by gas chromatography. The optimization procedure was performed using
      Box-Behnken design. The variables involved were: sample and extraction solvent
      volumes, consolute solvent volume and phase separator reagent concentration.
      Optimum results were obtained under the following conditions: sample volume of 5
      mL, extraction solvent volume of 55 microL, consolute solvent volume of 1 mL and
      phase separator reagent concentration; 5% (w/v). Under these conditions, the
      enrichment factors of 354, 311 and 300, dynamic linear ranges of 0.5-500, 1-500
      and 1-500 microg L(-1), and limit of detections (LODs) of 0.09, 0.09 and 0.1
      microg L(-1) were obtained for o-nitrotoluene, m-nitrotoluene and p-nitrotoluene,
      respectively. Finally, the method was successfully applied to the extraction and
      determination of MNTs in the waste water samples in the range of micrograms per
      liter with R.S.Ds.<13.2%.

PMID- 17560392
TI  - The prediction of total anthocyanin concentration in red-grape homogenates using
      visible-near-infrared spectroscopy and artificial neural networks.
AB  - This study compares the performance of partial least squares (PLS) regression
      analysis and artificial neural networks (ANN) for the prediction of total
      anthocyanin concentration in red-grape homogenates from their visible-near
      infrared (Vis-NIR) spectra. The PLS prediction of anthocyanin concentrations for
      new-season samples from Vis-NIR spectra was characterised by regression non
      linearity and prediction bias. In practice, this usually requires the inclusion
      of some samples from the new vintage to improve the prediction. The use of WinISI
      LOCAL partly alleviated these problems but still resulted in increased error at
      high and low extremes of the anthocyanin concentration range. Artificial neural
      networks regression was investigated as an alternative method to PLS, due to the
      inherent advantages of ANN for modelling non-linear systems. The method proposed
      here combines the advantages of the data reduction capabilities of PLS regression
      with the non-linear modelling capabilities of ANN. With the use of PLS scores as
      inputs for ANN regression, the model was shown to be quicker and easier to train
      than using raw full-spectrum data. The ANN calibration for prediction of new
      vintage grape data, using PLS scores as inputs, was more linear and accurate than
      global and LOCAL PLS models and appears to reduce the need for refreshing the
      calibration with new-season samples. ANN with PLS scores required fewer inputs
      and was less prone to overfitting than using PCA scores. A variation of the ANN
      method, using carefully selected spectral frequencies as inputs, resulted in
      prediction accuracy comparable to those using PLS scores but, as for PCA inputs,
      was also prone to overfitting with redundant wavelengths.

PMID- 17560391
TI  - Estimation of source spectra profiles and simultaneous determination of
      polycomponent in mixtures from ultraviolet spectra data using kernel independent
      component analysis and support vector regression.
AB  - A method that use kernel independent component analysis (KICA) and support vector
      regression (SVR) was proposed for estimation of source ultraviolet (UV) spectra
      profiles and simultaneous determination of polycomponents in mixtures. In KICA
      SVR procedure, the UV source spectra profiles were estimated using KICA, then the
      mixing matrix of the components were calculated using the estimated sources, and
      the calibration model was build using SVR based on the calculated mixing matrix.
      A simulated UV dataset of three-component mixtures was used to test the ability
      of KICA for estimating source spectra profiles from spectra data of mixtures. It
      was found that KICA has the potential power to estimate pure UV spectra profiles,
      and correlation coefficient of estimated sources correspond to the real adopted
      ones are better compared with that by FastICA and Infomax ICA. An UV dataset of
      polycomponent vitamin B was processed using the proposed KICA-SVR method. The
      results show that the estimated source spectra profiles are correlative with the
      real UV spectra of the components and chemically interpretable, and accurate
      results were obtained.

PMID- 17560393
TI  - Precision of micellar electrokinetic capillary chromatography in the
      determination of seven antibiotics in pharmaceuticals and feedstuffs.
AB  - Validation of analytical procedures is important for their efficient and reliable
      application. The International Conference on Harmonisation (ICH), Food and Drug
      Administration (FDA) and pharmacopoeia guidelines achieved a great deal in
      harmonising the definitions of the required validation characteristics. It is
      well known that poor reproducibility limits the practical implementation of
      capillary electrophoresis (CE). A precision study on four different MEKC methods
      was performed with 11 samples, containing seven antibiotics, by two analysts, in
      few days, on two capillary electrophoresis instruments. Five pharmaceutical
      preparations and three animal feeds were used. Precision was statistically
      analysed using migration time, peak area and height of each compound, as well as
      electroosmotic front (EOF). In 25 of 31 cases, the reproducibility of peak area,
      peak height and migration time was good (<5%). In most cases the reproducibility
      of peak area was much better than the reproducibility of peak height. The worst
      reproducibility that we observed was 12.7% for peak height and 7.6% for peak
      area.

PMID- 17560394
TI  - Signal processing of GC-MS data of complex environmental samples:
      characterization of homologous series.
AB  - Identification and characterization of homologous series by GC-MS analysis
      provide very relevant information on organic compounds in complex mixtures. A
      chemometric approach, based on the study of the autocovariance function,
      EACVF(tot), is described as a suitable tool for extracting molecular-structural
      information from the GC signal, in particular for identifying the presence of
      homologous series and quantifying the number of their terms. A data pre
      processing procedure is introduced to transform the time axis in order to display
      a strictly homogenous retention pattern: n-alkanes are used as external standard
      to stretch or shrink the original chromatogram in order to build up a linear GC
      retention scale. This addition can be regarded as a further step in the direction
      of a signal processing procedure for achieving a systematic characterization of
      complex mixture from experimental chromatograms. The EACVF(tot) was computed on
      the linearized chromatogram: if the sample presents terms of homologous series,
      the EACVF(tot) plot shows well-defined deterministic peaks at repeated constant
      interdistances. By comparison with standard references, the presence of such
      peaks is diagnostic for the presence of the ordered series, their position can be
      related to the chemical structure of the compounds, their height is the basis for
      estimating the number of terms in the series. The power of the procedure can be
      magnified by studying SIM chromatograms acquired at specific m/z values
      characteristic of the compounds of interest: the EACVF(tot) on these selective
      signals makes it possible to confirm the results obtained from an unknown mixture
      and check their reliability. The procedure was validated on standard mixtures of
      known composition and applied to an unknown gas oil sample. In particular, the
      paper focuses on the study of two specific classes of compounds: n-alkanes and
      oxygen-containing compounds, since their identification provides information
      useful for characterizing the chemical composition of many samples of different
      origin. The robustness of the method was tested in experimental chromatograms
      obtained under unfavorable conditions: chromatograms acquired in non-optimal
      temperature program conditions and chromatographic data affected by signal noise.

PMID- 17560395
TI  - Determination of Sudan dye residues in eggs by liquid chromatography and gas
      chromatography-mass spectrometry.
AB  - A sensitive and cheap high performance liquid chromatography (HPLC) with
      ultraviolet-visible (UV-VIS) was developed for the determination of Sudan dyes
      (I, II, III, and IV) residues in various types of eggs. The chromatographic
      separation was achieved on a reverse phase C18 column with gradient elution,
      using a mobile phase of 0.1% formic acid acetonitrile/0.1% formic acid aqueous
      solution; detector was set at 478 nm for Sudan I and 520 nm for Sudan II, III and
      IV. The suspected egg samples were derivatized with N,O-bis (trimethylsilyl)
      trifluoro-acetamide and confirmed by gas chromatography-mass spectrometry (GC-MS)
      in EI. Mass spectra of trimethylsilyl derivatives of the Sudan dyes were built up
      in EI mode. Recoveries of the Sudan dyes ranged between 79.8 and 95.7% in eggs by
      HPLC-UV, with all the relative standard deviations of less than 5%. Limit of
      detection (LOD), limit of quantification (LOQ) were in the range of 4.0-4.8 and
      12.3-13.8 microg kg(-1) in eggs, respectively. Identification and confirmation
      could be validated in the range of 2.0-4.2 microg kg(-1) with the GC-MS method.
      This method is suitable for routine fast monitoring, screening and confirmation
      of Sudan dyes residues in eggs, as mandated by regulatory agencies.

PMID- 17560396
TI  - Wrist trauma. Preface.

PMID- 17560397
TI  - Wrist anatomy and surgical approaches.
AB  - Appreciation and knowledge of anatomy as it relates to surgical approaches is
      critical for planning treatment of traumatic wrist injuries. This article
      discusses the pertinent anatomy and some of the more commonly used approaches to
      wrist trauma.

PMID- 17560398
TI  - Physical examination of the wrist.
AB  - Physical examination of the wrist requires knowledge of wrist anatomy and
      pathology to make a diagnosis or narrow the differential diagnosis. Symptoms are
      provoked by palpation and signs are produced by manipulation. Negative findings
      elsewhere in the wrist are important. Final diagnosis may require diagnostic
      imaging. By having all three methods of assessment agree one is assured of
      correct diagnosis. The physical examination of the wrist is not unlike that of
      other joints, in that a systematic approach includes observation, range of
      motion, palpation, and special tests.

PMID- 17560399
TI  - Distal radius fractures--classification of treatment and indications for surgery.
AB  - Distal radius fractures are common injuries. Multiple classification systems have
      highlighted the evolution of the understanding of distal radius fractures.
      Understanding the classifications of distal radius fractures is important in
      identifying the important aspects that affect their outcome. Surgical indications
      of distal radius fractures can be divided into the following categories: patient
      factors, fracture reduction, fracture stability, and the presence of associated
      injuries.

PMID- 17560400
TI  - Distal radius fractures: nonoperative and percutaneous pinning treatment options.
AB  - Nonoperative treatment of distal radial fractures by reduction and immobilization
      remains the most common treatment, based on the incidence of appropriate fracture
      types, as seen in many epidemiological studies in the literature. In this
      article, the indications, technique, predictors of failure, outcomes, and
      complications are reviewed. A variety of treatment options have been proposed for
      distal radial fractures that are predicted, or subsequently identified, to be too
      unstable for nonoperative management. Percutaneous pinning is an effective option
      for select fractures. The authors also review the indications, described
      techniques, complications and outcomes associated with this treatment option.

PMID- 17560401
TI  - External fixation of distal radius fractures.
AB  - Fractures of the distal radius are the most common fractures that occur in
      patients between ages 15 and 75 years. Many methods for treating displaced distal
      radius fractures are available. All forms of treatment involve obtaining fracture
      reduction, which may then be maintained by casting, functional bracing, external
      fixation, percutaneous pinning, internal fixation, or a combination of these
      methods. This article discusses the indications and technique of fracture
      treatment with external fixation and, when required, adjuvant percutaneous pins.

PMID- 17560402
TI  - Plating for distal radius fractures.
AB  - No area of fracture management has had such a recent explosion of new treatment
      modalities as distal radius plating. This explosion has largely been implant- and
      industry-driven, with little evidence-based research guiding the way. A perceived
      difficulty with commonly used modalities by the orthopedic community has been
      enough to drive an entire new set of options for distal radius fixation. A drift
      from dorsal to volar plating has occurred that has been unexamined by randomized
      research. Segment specific fixation has been a new mindset that has resulted in a
      novel plate line and has caused other manufacturers to redesign their product
      lines. Other novel approaches for proposed problems include locking plates, nail
      plate combinations, and others. This article outlines some of these options with
      a literature opinion and a clarification from the authors. A treatment plan for
      common fractures of the distal radius is also outlined.

PMID- 17560403
TI  - Management of post-traumatic malunion of fractures of the distal radius.
AB  - Distal radius malunions are a common cause of patient morbidity. This review of
      the literature surrounding distal radius malunion covers the demographics,
      pathologic anatomy, and indications for surgery, surgical techniques, and salvage
      options. Particular emphasis is placed on subject areas that have not been
      reviewed as extensively in previous articles, including: intra-articular
      malunion, computer-assisted techniques, bone graft alternatives, and volar fixed
      angle plate osteosynthesis.

PMID- 17560404
TI  - Complications of distal radius fractures.
AB  - Fractures occur at the distal end of the radius more frequently than at any other
      location. The reported complication rates of distal radius fractures in the
      literature vary from 6% to 80%. Complications may occur from the fracture or its
      treatment. This article reviews complications caused by distal radius fractures
      and their treatment. Complications are divided chronologically in to immediate,
      early (less than 6 weeks), and late (greater than 6 weeks).

PMID- 17560405
TI  - Acute scaphoid fractures.
AB  - Scaphoid fractures are a common problem encountered in clinical practice. This
      manuscript provides an algorithm for the diagnosis, evaluation, and treatment of
      acute scaphoid fractures.

PMID- 17560406
TI  - Management of scaphoid nonunions.
AB  - Scaphoid nonunions can exist with or without avascular necrosis of the proximal
      pole, and waist fractures may have an associated humpback deformity. CT best
      shows the deformity and bone loss, whereas MRI will show avascular necrosis.
      Operative treatment should be directed at correcting the deformity with open
      reduction and internal fixation and bone grafting. Vascularized bone grafts
      should be used in cases of avascular necrosis.

PMID- 17560407
TI  - Carpal bone fractures.
AB  - Carpal bone fractures make up a significant proportion of injuries to the wrist.
      The complex bone shape and articulations make diagnosis more difficult and missed
      injuries more common. This article reviews carpal bone fractures excluding the
      scaphoid.

PMID- 17560408
TI  - The diagnosis and treatment of scapholunate instability.
AB  - Scapholunate instability is the most common form of carpal instability. Pain
      produced by this condition is caused by the wrist's inability to sustain
      physiologic loads because of an injury to the linkage between the scaphoid and
      lunate. The term scapholunate instability may describe a wide spectrum of
      clinical conditions ranging from mild wrist dysfunction and partial ligamentous
      tear to debilitating pain with associated rupture of the scapholunate interosseus
      ligament complex. This article reviews the pathophysiology of scapholunate
      instability and its identification and treatment.

PMID- 17560409
TI  - Perilunate injuries.
AB  - Perilunate injuries are complex injuries of the bony and ligamentous structures
      of the wrist. They require operative management with careful restoration of
      carpal alignment and open reduction and internal fixation of associated
      fractures. Even with optimal treatment, mild to moderate dysfunction affects most
      patients.

PMID- 17560410
TI  - Traumatic injuries of the distal radioulnar joint.
AB  - Traumatic injuries of the distal radioulnar joint (DRUJ) may give rise to complex
      wrist pathologies. Substantial ongoing disability can arise should these injuries
      go unrecognized resulting in sub-optimal treatment and lack of appropriate
      rehabilitation. Injuries of the DRUJ may occur in isolation but more commonly are
      found with a fracture of the radius. These challenging DRUJ injuries may be
      simple or complex (irreducible or severe instability), acute or chronic. An
      adequate knowledge of the stabilizers of the DRUJ is essential in understanding
      treatment options. Traumatic instability of the DRUJ is reviewed and the anatomy
      and stabilizing factors are discussed. An algorithm to guide selection of
      treatment options in complex cases is presented.

PMID- 17560413
TI  - Pathophysiology of inflammatory bowel disease: an overview.
AB  - Inflammatory bowel disease, Crohn's disease, and ulcerative colitis are
      considered idiopathic diseases affecting the gastrointestinal tract. These two
      diseases are often considered together because of multiple similarities,
      including gastrointestinal inflammation, waxing and waning severity and symptoms,
      and unknown etiology. However, they have separate symptoms and microscopic
      characteristics as well as patterns within the gastrointestinal tract.

PMID- 17560414
TI  - Operative management of small bowel Crohn's disease.
AB  - Despite advances in medical treatment, most patients who have Crohn's disease of
      the small intestine need surgery at some point during the course of their
      disease. Surgery is currently indicated for intractable disease and complications
      of the disease (strictures, abscesses, fistulas, hemorrhage). There is increasing
      interest in nonsurgical and minimal access strategies of dealing with complicated
      disease, however. These new approaches may enable postponement of surgery to a
      more favorable time, or conversion of a two-stage procedure involving a stoma to
      a one-stage resection with anastomosis. A continuing challenge is prevention of
      disease recurrence postoperatively.

PMID- 17560415
TI  - Operative management of Crohn's disease of the colon including anorectal disease.
AB  - Evaluation and management of the patient who has Crohn's disease of the colon,
      rectum, and anus is challenging for even the most experienced provider. Because
      of its broad spectrum of presentation, recurrent nature, and potential for high
      morbidity, the surgeon needs to not only treat the acute situation but also keep
      in mind the potential long-term ramifications. Although there are exciting new
      medications and treatment modalities yielding promising results, surgery
      continues to remain at the forefront for the care of these patients. This article
      reviews various surgical options for the patient who has Crohn's disease of the
      colon, rectum, and perianal region with emphasis on symptomatic resolution and
      optimization of function.

PMID- 17560416
TI  - Elective and emergent operative management of ulcerative colitis.
AB  - Surgical therapy of ulcerative colitis is effective, safe, and provides an
      improved quality of life in those whose disease cannot be managed medically. In
      the elective setting, widespread acceptance of restorative proctocolectomy has
      made surgical therapy an attractive option in the overall management of
      ulcerative colitis. Enthusiasm for this procedure should be tempered by the
      acknowledgment of the significant incidence of pouchitis in the long term,
      however. Proctocolectomy with ileostomy remains a good surgical option for
      patients who are unsuitable for restorative procedures. The standard therapy for
      fulminant colitis or toxic megacolon remains subtotal colectomy with ileostomy.
      Patients undergoing subtotal colectomy are candidates for conversion to
      restorative procedures.

PMID- 17560417
TI  - Inflammatory bowel disease in the pediatric patient.
AB  - Inflammatory bowel disease (IBD) is a general term used to describe two chronic
      bowel disorders, Crohn's disease (CD) and ulcerative colitis (UC), both of which
      are characterized by autoimmune-related inflammation of the intestines. UC is
      limited to the colonic mucosa, whereas CD can involve any part of the intestinal
      tract from the mouth to the anus. The true etiology of UC and CD is still
      unknown, although extensive research has identified some genetic and
      environmental factors. This article discusses current clinical concepts of both
      diseases in the pediatric population.

PMID- 17560418
TI  - Associated neoplastic disease in inflammatory bowel disease.
AB  - The development of intestinal carcinoma in the setting of inflammatory bowel
      disease (IBD) has been recognized as an unsavory outcome of chronic inflammation
      of the bowel. Numerous studies have recently documented the clinical and
      morphologic features of malignant transformation in this closely-followed group
      of patients. This article highlights the recent findings of these population
      based studies with specific attention to surgical concepts and frames these data
      in the context of surgical approaches to cancer arising in inflammatory disease.
      Specifically, the authors address the pathobiology of malignant transformation,
      the management of colorectal cancer in inflammatory bowel disease, the
      development of dysplasia in ulcerative colitis, surveillance of patients who have
      IBD, chemoprevention of cancer, and special features of surgical oncologic
      management.

PMID- 17560419
TI  - Extra-intestinal manifestations of Crohn's disease.
AB  - Extra-intestinal manifestations occur in at least 25% of Crohn's disease
      patients. Some extra-intestinal manifestations, such as erythema nodusum and
      peripheral arthropathy, will wax and wane in keeping with bowel inflammation. The
      more severe cutaneous ulcerations, uveitis, and axial arthropathy may precede
      bowel disease or persist after it subsides. Screening may be appropriate for eye
      disease and for osteoporosis to prevent complications. Medical management for
      extra-intestinal manifestations is similar to treatment for the bowel symptoms of
      Crohn's disease, with corticosteroids the mainstay. Pain and depression are
      associated with inflammatory bowel disease, and their control benefits patients.
      Recent small studies with anti-tumor necrosis factor (TNF) agents are promising
      for most extra-intestinal manifestations of Crohn's disease, and may permit more
      steroid-sparing disease control in the future.

PMID- 17560420
TI  - Immunologic and molecular mechanisms in inflammatory bowel disease.
AB  - Molecular and immunologic mechanisms underlying inflammation in inflammatory
      bowel disease (IBD) are largely unknown. Recent studies have helped better
      characterize genetic and environmental factors associated with colitis.
      Discoveries of genetic variants have confirmed that IBD is a bacteria and
      cytokine-driven pathologic immune response. Data have demonstrated that certain T
      cell subsets are important in executing the inflammatory cascade. Insufficient
      regulatory cell activity or modulatory cytokine production results in
      unrestrained inflammation. Biologic agents that block inflammatory cytokines
      (anti-TNFalpha antibodies) have been used successfully to treat IBD. Recent
      advances have also identified mucosal regulatory pathways.

PMID- 17560421
TI  - Current medical therapy for chronic inflammatory bowel diseases.
AB  - Chronic idiopathic inflammatory bowel diseases (IBD) include Crohn's disease
      (CD), ulcerative colitis (UC), and colonic IBD type unclassified (IBDU). This
      article focuses upon current medical therapies for adult CD and UC, and is
      organized according to therapy for the corresponding disease type, stage, and
      severity.

PMID- 17560422
TI  - Novel and future medical management of inflammatory bowel disease.
AB  - The treatment of inflammatory bowel disease (IBD) is undergoing rapid and
      profound change. Entirely new approaches are being developed that reflect a
      greater understanding of how to control the inflammatory process. These began
      with inflixumab therapy for Crohn's disease. Additional tumor necrosis antibodies
      will soon be employed, and other biological agents are being investigated.
      Probiotics, helminth ova therapy, alternative and complementary treatments,
      leukocytophoresis, and bone-marrow and stem-cell transplantation are additional
      exciting regimens that are being explored. Although some of these approaches
      provide marked improvement in these parameters, others are unproven or fraught
      with adverse effects and complications. Still, control of ulcerative colitis and
      Crohn's is improving with more changes likely to come.

PMID- 17560423
TI  - Endoscopy/surveillance in inflammatory bowel disease.
AB  - Patients with chronic colitis from inflammatory bowel disease (IBD) have an
      increased risk of colorectal cancer (CRC). Previously, to ameliorate this,
      prophylactic total colectomy was offered to patients who had chronic ulcerative
      colitis (UC); however, research has identified less invasive management options
      through better understanding of the pathogenesis of cancer in chronic
      inflammation, a more uniform histologic diagnosis by pathologists, and proper
      surveillance colonoscopy techniques. This article reviews the pathogenesis of
      neoplasia in IBD, and then reviews the risk factors for CRC in IBD, surveillance
      guidelines and their limitations, surveillance techniques, ileal pouch dysplasia,
      and chemoprevention. Although data for CRC risk in Crohn's disease (CD) are not
      as extensive, it has been suggested that the risks are comparable to UC.

PMID- 17560424
TI  - Pathologist surgeon interface in idiopathic inflammatory bowel disease.
AB  - To accomplish the important tasks of establishing the diagnosis of inflammatory
      bowel disease and separating ulcerative colitis from Crohn's disease, there needs
      to be close cooperation among gastroenterologist, surgeon, and pathologist.
      Paying close attention to details of sampling and historical information plays a
      major role in this task, and an equally great role in identifying dysplasia and
      determining its significance. Important elements in this clinical-pathology
      interface are discussed in this article.

PMID- 17560425
TI  - Legal and illegal organ donation.

PMID- 17560426
TI  - A new institute for global health evaluations.

PMID- 17560427
TI  - Reed Elsevier and defence exhibitions: an announcement.

PMID- 17560428
TI  - Abortion is for women.

PMID- 17560429
TI  - Outcomes of transplantation in children with acute leukaemia.

PMID- 17560430
TI  - Improved diagnosis of tuberculosis by better sputum quality.

PMID- 17560431
TI  - Clinical trial registration: looking back and moving ahead.

PMID- 17560432
TI  - Clinical update: syphilis in adults.

PMID- 17560433
TI  - High spirits.

PMID- 17560435
TI  - Tumour lysis syndrome in a patient with renal-cell carcinoma treated with
      sunitinib malate.

PMID- 17560436
TI  - Chest-compression-only or full cardiopulmonary resuscitation?

PMID- 17560437
TI  - Chest-compression-only or full cardiopulmonary resuscitation?

PMID- 17560439
TI  - Chest-compression-only or full cardiopulmonary resuscitation?

PMID- 17560440
TI  - Chest-compression-only or full cardiopulmonary resuscitation?

PMID- 17560441
TI  - Type I and type IV allergy to insulin detemir.

PMID- 17560443
TI  - Gerry Robinson and exaggeration.

PMID- 17560444
TI  - Public-health approach to eating disorders.

PMID- 17560445
TI  - UK governmental interference in surgical training.

PMID- 17560446
TI  - Efficacy of two intervals and two routes of administration of misoprostol for
      termination of early pregnancy: a randomised controlled equivalence trial.
AB  - BACKGROUND: The most effective route and best interval between several doses of
      misoprostol to induce abortion have not been defined. Our aim was to assess the
      effects of the interval between multiple doses of misoprostol and the route of
      administration to terminate pregnancy. METHODS: 2066 healthy pregnant women
      requesting medical abortion with 63 days or less of gestation were randomly
      assigned within 11 gynaecological centres in six countries to the four treatment
      groups (three doses of 0.8 mg misoprostol given sublingually at 3-h intervals,
      vaginally 3 h, sublingually 12 h, and vaginally 12 h), stratifying by gestational
      age. This was an equivalence trial with a 5% margin of equivalence. The primary
      endpoints were efficacy of treatment to achieve complete abortion and to
      terminate pregnancy. The main efficacy analysis excluded women lost to follow-up.
      This trial is registered as an International Standard Randomised Controlled
      Trial, number ISRCTN10531821. FINDINGS: Efficacy outcomes were analysed for 2046
      women (99%), excluding 20 lost to follow-up. Complete abortion rates at 2-week
      follow-up were recorded for 431 (84%) in the sublingual and for 434 (85%) women
      in the vaginal group when misoprostol was given at 3-h intervals (difference
      0.4%, 95% CI -4.0 to 4.9, p=0.85 equivalence shown), and for 399 (78%) in the
      sublingual and for 425 (83%) in the vaginal 12-h groups (4.6%, -0.2 to 9.5,
      p=0.06, equivalence not shown). In the 3-h groups, pregnancy continued in 29 (6%)
      women after sublingual and in 20 (4%) women after vaginal administration
      (difference 1.8%, 95% CI -0.8 to 4.4, p=0.19, equivalence shown); in the 12-h
      groups it continued in 47 (9%) after sublingual and in 25 (5%) after vaginal
      administration (4.4%, 1.2-7.5, p=0.01, vaginal better than sublingual).
      Differences for complete abortion between intervals for sublingual and vaginal
      routes were 6% (95% CI 1.0-10.6, p=0.02, 3 h better than 12 h) and 2% (-2.9 to
      6.1, p=0.49, equivalence not shown), respectively; for continuing pregnancies
      they were 4% (0.4-6.8, p=0.03, 3 h better than 12 h) and 1% (-1.5 to 3.5, p=0.44,
      equivalence shown), respectively. INTERPRETATION: Administration interval can be
      chosen between 3 h and 12 h when misoprostol is given vaginally. If
      administration is sublingual, the intervals between misoprostol doses need to be
      short, but side-effects are then increased. With 12-h intervals, vaginal route
      should be used, whereas with 3-h intervals either route could be chosen.

PMID- 17560447
TI  - Outcomes of transplantation of unrelated donor umbilical cord blood and bone
      marrow in children with acute leukaemia: a comparison study.
AB  - BACKGROUND: Although umbilical cord blood is an accepted alternative to bone
      marrow for transplantation, allele-matched bone marrow is generally regarded as
      the preferred graft source. Our aim was to assess leukaemia-free survival after
      transplantations of these alternatives compared with present HLA-matching
      practices, and to assess the relative effect of cell dose and HLA match, and
      their potential interaction on leukaemia-free survival after cord-blood
      transplantation. METHODS: Outcomes of 503 children (<16 years) with acute
      leukaemia and transplanted with umbilical cord blood were compared with outcomes
      of 282 bone-marrow recipients. All transplantation took place in the USA.
      Recipients of umbilical cord blood were transplanted with grafts that were HLA
      matched (n=35) or HLA-mismatched for one (n=201) or two antigens (n=267) (typing
      at antigen level for HLA-A and HLA-B, and allele level for HLA-DRB1). Bone-marrow
      recipients were transplanted with grafts that were matched at the allele level
      for HLA-A, HLA-B, HLA-C, and HLA-DRB (n=116), or mismatched (n=166). The primary
      endpoint was 5-year leukaemia-free survival. FINDINGS: In comparison with allele
      matched bone-marrow transplants, 5-year leukaemia-free survival was similar to
      that after transplants of umbilical cord blood mismatched for either one or two
      antigens and possibly higher after transplants of HLA-matched umbilical cord
      blood. Transplant-related mortality rates were higher after transplants of two
      antigen HLA-mismatched umbilical cord blood (relative risk 2.31, p=0.0003) and
      possibly after one-antigen HLA-mismatched low-cell-dose umbilical-cord-blood
      transplants (1.88, p=0.0455). Relapse rates were lower after two-antigen HLA
      mismatched umbilical-cord-blood transplants (0.54, p=0.0045). INTERPRETATION:
      These data support the use of HLA-matched and one- or two-antigen HLA-mismatched
      umbilical cord blood in children with acute leukaemia who need transplantation.
      Because better HLA matching and higher cell doses significantly decrease the risk
      of transplant-related mortality after umbilical-cord-blood transplantation,
      greater investment in large-scale banking is needed to increase HLA diversity.

PMID- 17560448
TI  - Improvement of tuberculosis case detection and reduction of discrepancies between
      men and women by simple sputum-submission instructions: a pragmatic randomised
      controlled trial.
AB  - BACKGROUND: In several settings, women with suspected tuberculosis are less
      likely to test smear positive than are men. Submission of poor-quality sputum
      specimens by women might be one reason for the difference between the sexes. We
      did a pragmatic randomised controlled trial to assess the effect of sputum
      submission instructions on female patients. METHODS: 1494 women and 1561 men with
      suspected tuberculosis attending the Federal Tuberculosis Centre in Rawalpindi,
      Pakistan, were randomly assigned between May and July, 2005 either to receive
      sputum-submission guidance before specimen submission or to submit specimens
      without specific guidance, according to prevailing practice. Of enrolled
      patients, 133 (4%) declined to participate. The primary outcome measure was the
      proportion of instructed and non-instructed women testing smear positive.
      Intention-to-treat analysis was undertaken on the basis of treatment allocation.
      This study is registered with the International Standard Randomised Controlled
      Trial number 34123170. FINDINGS: Instructed women were more likely to test smear
      positive than were controls (Risk ratio 1.63 [95% CI 1.19-2.22]). Instructions
      were associated with a higher rate of smear-positive case detection (58 [8%] in
      controls vs 95 [13%] in the intervention group; p=0.002), a decrease in spot
      saliva submission (p=0.003), and an increase in the number of women returning
      with an early-morning specimen (p=0.02). In men, instructions did not have a
      significant effect on the proportion testing smear positive or specimen quality.
      INTERPRETATION: In the Federal Tuberculosis Centre in Rawalpindi, lower smear
      positivity in women than in men was mainly a function of poor-quality specimen
      submission. Smear positivity in women was increased substantially by provision of
      brief instructions. Sputum-submission guidance might be a highly cost-effective
      intervention to improve smear-positive case detection and reduce the disparity
      between the sexes in tuberculosis control in low-income countries.

PMID- 17560449
TI  - Vulvovaginal candidosis.
AB  - Despite therapeutic advances, vulvovaginal candidosis remains a common problem
      worldwide, affecting all strata of society. Understanding of anti-candida host
      defence mechanisms in the vagina has developed slowly and, despite a growing list
      of recognised risk factors, a fundamental grasp of pathogenic mechanisms
      continues to elude us. The absence of rapid, simple, and inexpensive diagnostic
      tests continues to result in both overdiagnosis and underdiagnosis of
      vulvovaginal candidosis. I review the epidemiology and pathogenesis of this
      infection, and also discuss management strategies.

PMID- 17560450
TI  - Dark green blood in the operating theatre.

PMID- 17560451
TI  - New diseases derived or associated with the tight junction.
AB  - The space between neighboring epithelial cells is sealed by the tight junction
      (TJ). When this seal is leaky, such as in the proximal tubule of the kidney or
      the gallbladder, substances may cross the epithelium between the cells
      (paracellular pathway). Yet, when TJs are really hermetic, as is the case in the
      epithelium of the urinary bladder or the colon, substances can mainly cross the
      epithelium through the transcellular pathway. The structure of the TJ involves
      (so far) some 50-odd protein species. Failure of any of these components causes a
      variety of diseases, some of them so serious that fetuses are not viable. A fast
      growing number of diseases are recognized to depend or involve alterations in the
      TJ. These include autoimmune diseases, in which intestinal TJs allow the passage
      of antigens from the intestinal flora, challenging the immune system to produce
      antibodies that may cross react with proteins in the brain, thyroid gland or
      pancreas. TJs are also involved in cancer development, infections, allergies,
      etc. The present article does not catalogue all TJ diseases known so far, but
      describes one of each type as illustration. It also depicts the efforts being
      made to find pharmaceutical agents that would seal faulty TJs or release their
      grip to allow for the passage of large molecules through the upper respiratory
      and digestive tracts, such as insulin, thyroid, appetite-regulatory peptide, etc.

PMID- 17560452
TI  - Statins and peripheral arterial disease: effects on claudication, disease
      progression, and prevention of cardiovascular events.
AB  - Peripheral arterial disease (PAD) of the lower limbs is the third most important
      site of atherosclerotic disease alongside coronary heart disease (CHD) and
      cerebrovascular disease (CVD). Best medical treatment is beneficial even in
      patients who eventually need invasive treatment, as the safety, immediate
      success, and durability of intervention is greatly improved in patients who
      adhere to best medical treatment. In recent years, a number of studies have
      suggested that the ACE-inhibitor ramipril and different statins, together with
      antiplatelet drugs, reduce cardiovascular morbidity and mortality in PAD.
      Patients with PAD are really a category of patients with a very high
      cardiovascular risk burden for fatal and nonfatal cerebrovascular and
      cardiovascular events; therefore, they need to be treated not only for local
      problems deriving from arteriopathy (intermittent claudication, rest pain and/or
      ulcers) but, above all, for preventing vascular events. Statins not only lower
      the risk of vascular events, but they also improve the symptoms associated with
      PAD. Statins exert beneficial pleiotropic effects on hemostasis, vasculature and
      inflammatory markers; there is also evidence that statins improve renal function
      considering that the plasma creatinine level is considered as an emerging
      vascular risk factor.

PMID- 17560453
TI  - Oral administration of avocado soybean unsaponifiables (ASU) reduces ischemic
      damage in the rat hippocampus.
AB  - BACKGROUND: The beneficial effects of avocado/soybean unsaponifiables (ASU) are
      known as an antiarthritic agent. This experimental study presents the effects of
      ASU on oxidant/antioxidant systems and the number of apoptotic neurons of
      hippocampal formation after ischemia and reperfusion. METHODS: Eighteen rats were
      divided into three equal groups: group I rats were used as controls; group II
      rats were fed with standard diet and group III rats were fed with standard diet
      plus ASU pills for 10 days. One day after electrocauterization of bilateral
      vertebral arteries for groups II and III, bilateral common carotid arteries were
      occluded for 30 min and then reperfused for 30 min. After these procedures, rats
      of all groups were sacrificed. The levels of malondialdehyde (MDA) and nitric
      oxide (NO) and activities of superoxide dismutase (SOD) and catalase (CAT) were
      measured in the left hippocampus. The number of apoptotic neurons was counted by
      Tunel method in histological samples of right hippocampus. RESULTS: MDA and NO
      levels increased in group II compared with group I rats (p = 0.002, p = 0.015).
      In group III, MDA and NO levels decreased as compared to group II (p = 0.041, p =
      0.002). SOD and CAT activities increased in group III as compared to group II
      rats (p = 0.002, p = 0.002). The number of apoptotic neurons was lower in group
      III as compared to group II rats. CONCLUSIONS: The present findings suggest that
      ASU could decrease oxidative stress and apoptotic changes in ischemic rat
      hippocampus. Dietary supplementation of ASU may be beneficial to prevent or
      ameliorate ischemic cerebral vascular disease.

PMID- 17560454
TI  - Age effect on human aortic valvular glycoproteins.
AB  - BACKGROUND: The aortic valve has been the subject of many hemodynamic studies
      but, to our knowledge, posttranslational modification of human valve proteins has
      not yet been studied. Thus, the aim of this study was to determine whether any
      age-related changes in the protein composition of normal human aortic valves and
      their glycosylation pattern could be observed. METHODS: Aortic valves harvested
      from male cadaveric donors free of cardiovascular diseases were divided into four
      age groups: I, mean age 21 years; II, 30 years; III, 41 years; IV, 51 years.
      Proteins were separated by SDS-PAGE and transferred to PVDF membranes.
      Identification of monosaccharide moieties or oligosaccharide units was performed
      with the use of eight lectins of narrow specificity: Galantus nivalis agglutinin,
      Sambucus nigra agglutinin, Maackia amurensis agglutinin, Datura stramonium
      agglutinin, Aleuria aurantia agglutinin, Arachis hypogeae agglutinin, Phaseolus
      vulgaris agglutinin, and Lycopersicon esculentum agglutinin. RESULTS: Isolated
      proteins showed no age-related changes in SDS-PAGE protein profile, contrary to
      their glycosylation. Protein sialylation, number of tri/tetraantennary complex
      glycans, proteins having terminal galactose and polylactosaminyl units increased
      with age, whereas protein fucosylation showed the opposite relationship.
      Moreover, groups III and IV possessed a larger number of proteins bearing high
      mannose and/or hybrid-type glycans, and the quantity of these structures seemed
      to change, in particular proteins, with the age of donors. CONCLUSIONS: Our
      results clearly demonstrate that glycosylation profile in human aortic proteins
      is associated with the age of the donor.

PMID- 17560455
TI  - Effects of stobadine and vitamin E in diabetes-induced retinal abnormalities:
      involvement of oxidative stress.
AB  - BACKGROUND: Because hyperglycemia-induced oxidative stress may be a cause of
      retinopathy, this study examined the hypothesis that administration of exogenous
      antioxidants, stobadine (ST) and vitamin E (vitE), can restore retinal
      abnormalities in experimental diabetes. METHODS: Normal and streptozotocin (STZ)
      induced male Wistar rats received daily intraoral doses of ST (24.7 mg/kg) and
      vitE (alpha-dl-tocopherol acetate, 400-500 IU/kg) individually or in combinations
      for 8 months. The biochemical parameters including aldose reductase enzyme (AR)
      activity and lipid peroxidation (MDA), and histopathological changes such as
      retinal capillary basement membrane thickness (RCBMT) and vascular endothelial
      growth factor (VEGF) expression were evaluated. RESULTS: A 37.99% increase in
      RCBMT was observed in rats after 8 months diabetes duration. The increase in
      RCBMT was 12.34% in diabetic rats treated with ST and 23.07% in diabetic rats
      treated with vitE. In diabetic rats treated with antioxidant combination, just a
      4.38% increase was observed in RCBMT. The excess VEGF immunoreactivity and
      increased MDA and AR activity determined in diabetic retina were significantly
      attenuated by individual antioxidant treatments. Although both antioxidants
      decreased blood glucose, HbA1c, fructosamine and triglyceride levels in diabetic
      rats, poor glycemic control was maintained in all experimental groups during the
      treatment period. However, the antioxidant combination led to almost complete
      amelioration in retinal MDA and RCBMT in diabetic rats. CONCLUSIONS: The ability
      of antioxidant combination to arrest retinal abnormalities and lipid peroxidation
      even in the presence of poor glycemic control might advocate the key role of
      direct oxidative damage and the protective action of antioxidants in retinal
      alterations associated with diabetic retinopathy.

PMID- 17560456
TI  - Selective cardiac neuroadrenergic abnormalities in hypertensive patients with
      left ventricular hypertrophy.
AB  - BACKGROUND: Increased sympathetic drive to the heart might contribute to the
      development and progression of myocardial damage in hypertensive patients (HTs).
      This study assessed the possible presence of abnormalities in myocardial uptake
      of (123)I-metaiodobenzylguanidine (MIBG), a marker of sympathetic activity, in
      HTs with left ventricular hypertrophy (LVH). METHODS: Eleven HTs with LVH and 10
      matched normotensive controls underwent clinical and laboratory examination, as
      well as LVH determination by echocardiography. The presence of myocardial
      ischemia was ruled out by exercise stress testing. Global and regional myocardial
      uptake of (123)I-MIBG was determined in both groups using planar and single
      proton emission tomography scintigraphy. In addition, thallium-201 (Tl-201)
      myocardial scintigraphy was performed in HTs. The heart/mediastinum (H/M) ratio
      on planar (123)I-MIBG images at different time points was compared between HTs
      and controls. Moreover, regional cardiac uptake of (123)I-MIBG was compared
      between groups and, within the HTs group, with regional Tl-201 uptake. RESULTS:
      At all study times, the H/M ratio was lower in HTs than in controls (all p
      <0.05). A significant reduction in (123)I-MIBG uptake in the mid-inferolateral
      and mid-inferior segments was observed in HTs compared to controls. Also, a
      significant reduction in (123)I-MIBG uptake compared to Tl-210 uptake was
      observed in non-septal segments of HTs. CONCLUSIONS: Cardiac abnormalities in
      global and regional uptake of (123)I-MIBG, as well as impaired (123)I-MIBG
      compared to Tl-201 uptake, are present in HTs with LVH. Given the effect of
      sympathetic nervous system on the heart, these abnormalities might play a role in
      hypertension-related cardiac damage.

PMID- 17560457
TI  - Role of insulin-like growth factor-1 in colon cancerogenesis: a case-control
      study.
AB  - BACKGROUND: Our aim was to establish whether individuals who developed colon
      cancer have elevated blood levels of insulin-like growth factor-1 (IGF-1).
      METHODS: This was a case/control study in which 52 patients with colon cancer and
      a corresponding control group were investigated. Data on age, weight, height, and
      sex of subjects were recorded and levels of IGF-1 and growth hormone, as well as
      insulin and C-peptide levels, were measured in the morning before eating, 90 min
      after breakfast and again 90 min after lunch. RESULTS: We found significantly
      higher levels of IGF-1 in blood of colon cancer patients compared to the control
      group. No differences in the levels of growth hormone, insulin and C-peptide in
      blood were found between colon cancer patients and the control group. It was
      found that the increase of IGF-1 level was followed by a 3.15-fold increased risk
      for developing colon cancer. There were no differences in the levels of IGF-1 in
      blood in all three measurements in the group of colon cancer patients, whereas
      differences were found in the control group. We found differences in the levels
      of insulin and C-peptide in blood in all three measurements in both groups of
      patients. No differences were found in the levels of growth hormone in blood in
      all three measurements in both groups of patients. CONCLUSIONS: The results of
      this study suggest a positive correlation between the increased levels of IGF-1
      and colon cancer and are thus consistent with the hypothesis that the level of
      IGF-1 plays an important role in the development of colon cancer.

PMID- 17560458
TI  - Functional characteristics of neutrophils and mononuclear cells from tuberculosis
      patients stimulated in vitro with heat killed M. tuberculosis.
AB  - BACKGROUND: The major protective immune response against intracellular bacteria,
      such as Mycobacterium tuberculosis, is a cell-mediated immunity involving
      neutrophils (PMNs) and peripheral mononuclear cells (MCs), contributing to the
      clearance of this microorganism and the resolution of the infection. This study
      was addressed to evaluate PMNs and MCs for their bactericidal function. METHODS:
      The sample comprised 14 tuberculosis (TB) inpatients (HIV-), and 10 healthy
      controls (HCo). Peripheral PMNs and MCs were separated by Ficoll-Hypaque and
      cultured in RPMI with or without heat-killed Mycobacterium tuberculosis (HK Mtb).
      Respiratory burst (RB), CD11b, IL-8 and TNFalpha receptor expression were
      assessed by flow cytometry in cells undergoing stimulation or not. Presence of IL
      8 and TNFalpha in cell culture supernatants was determined by ELISA. RESULTS: TB
      patients had a lower RB response than HCo for both cell types (MCs, p <0.05,
      PMNs, p <0.01) regardless of HK Mtb stimulation. Compared to HCo, PMNs and MCs
      from TB patients presented a reduced CD11b expression, with the two subject
      groups showing a decrease in this marker expression following HK. Mtb was added
      to both cell cultures. Whereas fewer IL-8 and TNFalpha receptors were found when
      studying MCs and PMNs from TB patients, antigen stimulation significantly raised
      the expression for both cytokine receptors. Culture supernatants from MCs and
      PMNs of TB patients contained increased amounts of IL-8 and TNFalpha.
      CONCLUSIONS: The present findings may provide some explanation as to the
      different roles played by PMNs and MCs in TB immunopathology.

PMID- 17560459
TI  - Circulating levels of adhesion molecules in chronic kidney disease correlate with
      the stage of renal disease and with C-reactive protein.
AB  - BACKGROUND: Patients with chronic renal failure (CRF) suffer from a series of
      complications linked to the atherosclerotic process in which the endothelial
      dysfunction mediated by the activation of some adhesion molecules plays an
      important role. This study aims to evaluate circulating levels of intercellular
      adhesion molecules-1 (ICAM-1) and vascular cell adhesion molecules-1 (VCAM-1) in
      patients with predialysis CRF, on maintenance hemodialysis (HD) and after kidney
      transplantation (KTx) and to correlate them with some inflammation and
      nutritional indexes. METHODS: Thirty two patients with predialysis CRF, 30 on
      maintenance HD, 36 after KTx and 28 subjects as a control group (C) were included
      in this study. Circulating levels of ICAM-1 and VCAM-1 were assayed using a
      specific sandwich ELISA kit. As inflammation indexes, TNFalpha and C-reactive
      protein (CRP) and, as nutritional indexes, body mass index (BMI), serum albumin,
      cholesterol, triglycerides, and fibrinogen (F) were evaluated. RESULTS: Serum
      levels of ICAM-1 and VCAM-1 were progressively higher from C to KTx patients, to
      those with CRF and those on HD (ANOVA for both; p <0.001). TNFalpha values were
      lower in HD subjects than in CRF patients, even if in both groups TNFalpha levels
      were greater than in Tx and control subjects. F and CRP were higher in CRF and HD
      vs. Tx and control subjects (ANOVA for both p <0.001). No significant
      correlations were observed between soluble adhesion molecules, albumin and
      cholesterol, whereas significant correlations were found between CRP and ICAM-1
      (r = 0.41; p <0.01), CRP and VCAM-1 (r = 0.39; p <0.01) and between CRP and
      TNFalpha (r = 0.42; p <0.01). These correlations remained statistically
      significant even after adjustment for age and blood pressure (all p <0.01). BMI
      did not differ in the three patient groups. CONCLUSIONS: Circulating levels of
      adhesion molecules in our study correlated positively with the stage of disease
      and with one of the inflammatory indexes (CRP), but not with nutritional indexes
      such as BMI, cholesterol and albumin. The clinical significance of our findings
      warrants further investigation.

PMID- 17560460
TI  - MDR1 C3435T polymorphism in patients with breast cancer.
AB  - BACKGROUND: The human multidrug-resistant gene (MDR1) encodes P-glycoprotein
      (Pgp), a membrane-bound efflux transporter conferring resistance to a number of
      natural cytotoxic drugs and potentially toxic xenobiotics. Single-nucleotide
      polymorphisms (SNPs) in MDR1 gene are associated with phenotypic variation in Pgp
      expression levels of tissue. SNPs may alter the physiological protective role of
      Pgp and, therefore, influence disease risk. METHODS: In our study we identified
      the MDR1 C3435T polymorphism in breast cancer patients (n = 57) and healthy
      subjects (n = 50). DNA was extracted from peripheral blood samples by standard
      phenol/chloroform extraction method. Polymerase chain reaction-restriction
      fragment length polymorphism was used for the detection of C3435T single
      nucleotide polymorphism. RESULTS: We obtained CC, CT and TT genotype frequencies
      in breast cancer patients as 12.3%, 57.9% and 29.8%, respectively. In the control
      group, frequencies of genotypes were found as 36% for CC, 46% for CT and 18% for
      TT. We observed difference in SNPs in MDR1 gene C3435T polymorphism between
      breast cancer patients and healthy controls (chi(2) = 8.66, df = 2, p = 0.013).
      The C allele frequency was found in 41.2% and the T allele frequency was found in
      58.8%. C3435T MDR1 gene allele frequencies in breast cancer patients as compared
      to results in control group were as follows: [OR = 1.5 (95% CI: 1.09-1.96)]. In
      the patient group, T allele frequency was significantly higher than controls (p
      <0.01). Clinicopathological parameters of patients with breast cancer were
      compared for C3435T polymorphism. We did not find any significant difference
      between clinicopathological parameters and MDR1 phenotype of breast cancer
      patients. The progression-free survival rate in a subgroup analysis based on MDR1
      genotypes with CC genotype was 71.4%, CT genotype was 75.7%, and TT genotype was
      88.2%, respectively. This difference was not statistically significant (log rank
      p = 0.63). CONCLUSIONS: Results of the present study demonstrated a 1.5-fold
      increased risk for development of breast cancer in T allele carriers.

PMID- 17560461
TI  - Synergistic effects between Q192R polymorphism of paraoxonase 1 gene and some
      conventional risk factors in premature coronary artery disease.
AB  - BACKGROUND: Genetic susceptibility to coronary artery disease (CAD) may be
      determined by polymorphic variants of genes encoding isoforms involved in the
      processes important in the pathogenesis of atherosclerosis, including lipoprotein
      oxidation. Participation of single polymorphic variants is relatively small;
      however, its significance may increase in the presence of specific environmental
      background. The aim of the study was an evaluation of a possible association
      between R192Q polymorphism of PON1 gene and CAD as well as interactions between
      polymorphic variants and conventional risk factors of CAD in determining the risk
      of the disease. METHODS: We studied 358 subjects: 178 patients with
      angiographically confirmed CAD and 180 blood donors without history of CAD.
      Polymorphisms were genotyped using PCR-RFLP method. RESULTS: We observed
      statistically significant differences in the frequencies of Q allele and Q allele
      carriers of PON1 gene between CAD and controls. We also found a strong
      synergistic effect between Q allele carrier state and smoking, as well as Q
      allele carrier state and elevated level of total cholesterol. CONCLUSIONS: The
      present study revealed an association between carrier state of Q allele of PON1
      gene and coronary artery disease as well as synergistic effects between genotype
      and some conventional risk factors, mainly smoking and elevated level of total
      cholesterol.

PMID- 17560462
TI  - Interleukin-6 polymorphisms, Helicobacter pylori infection in adult Brazilian
      patients with chronic gastritis and gastric adenocarcinoma.
AB  - BACKGROUND: The discovery of Helicobacter pylori offered the etiologic agent of
      the initiating event of the inflammatory cascade. It has been confirmed that the
      development of gastric cancer spans over several decades sequentially starting
      with the acquisition of H. pylori infection and the development of chronic
      gastritis. The IL-6 gene (Il-6), inflammatory cytokine and the single-nucleotide
      polymorphisms (SNPs) at the 5' flanking region of the Il-6 gene promoter (G or C
      at -174 base and at -572 or -597 C or A) have been identified with increased Il-6
      levels. METHODS: Biopsies were collected from 168 patients. SNPs in Il-6-174 were
      analyzed by PCR-RFLP. RESULTS: Promoter SNP of Il-6 at -174 base were within
      Hardy-Weinberg equilibrium. We did not find any association between the
      frequencies of -174 polymorphism with specific histological type of gastric
      adenocarcinoma, but the G (guanine) allele at -174 was significantly higher in
      gastric adenocarcinoma than in patients with chronic gastritis. CONCLUSIONS: We
      observed an association between GG allele on -174 base with gastric cancer.

PMID- 17560463
TI  - 1484insG polymorphism of the PTPN1 gene is associated with insulin resistance in
      an Iranian population.
AB  - BACKGROUND: Protein tyrosine phosphatase 1B (PTP1B), encoded by the PTPN1 gene,
      efficiently dephosphorylates the insulin receptor, and attenuates insulin
      signaling. Recently, a 1484insG variant of the PTPN1 gene has been associated
      with an increased risk of metabolic syndrome in an Italian population that has
      not been confirmed in the subsequent studies. The purpose of this study was to
      investigate the association of 1484insG polymorphism of the PTPN1 with obesity,
      insulin resistance, type 2 diabetes and other cardiovascular-related traits in an
      Iranian population. METHODS: The genotypes of 1484insG variant were determined by
      PCR-RFLP method in 696 unrelated subjects including 412 subjects with normal
      glucose tolerance and normal fasting glucose and 284 type 2 diabetic patients.
      RESULTS: The allelic frequency of 1484insG polymorphism among type 2 diabetic
      patients and non-diabetic subjects was 4.9 and 4.1%, respectively (p = 0.475). In
      type 2 diabetic patients, among quantitative traits, no significant difference in
      anthropometric and biochemical parameters was seen between the wild-type and
      heterozygous 1484insG genotypes in male and female groups and in non-diabetic
      subjects, male carriers of 1484insG allele had significantly higher fasting
      insulin (p = 0.003), cholesterol (p = 0.012), LDL-C (p = 0.037), apo B (p =
      0.015), and HOMA-IR (p = 0.011) levels compared to the individuals carrying the
      wild-type genotype. Among non-diabetic female individuals, only body mass index
      was significantly higher in 1484insG subjects compared to the wild-type
      individuals (p = 0.007). CONCLUSIONS: Our results from a sample of Iranian type 2
      diabetes cases and controls provide evidence that the 1484insG genotype of the
      PTPN1 gene may be associated with insulin resistance and other cardiovascular
      risk factors in non-diabetic male subjects.

PMID- 17560464
TI  - Serum leptin concentration, adiposity, and body fat distribution in Mexican
      Americans.
AB  - BACKGROUND: Leptin is strongly associated with adiposity and few studies have
      investigated its role in Mexican-Americans. The aims of this study were to
      examine the association of serum leptin concentration with adiposity and body fat
      distribution in Mexican-Americans and to develop a predictive model of serum
      leptin concentration for this ethnic group. METHODS: Three hundred fifty-two
      college students (242 women, 110 men; age 18-30 years) were evaluated in this
      cross-sectional study. Body fat content was assessed using bioelectrical
      impedance analysis. Correlation between serum leptin levels and several markers
      of adiposity and body fat distribution were examined in both men and women.
      Multiple regression analysis was performed to create the predictive model.
      RESULTS: Women had higher serum leptin concentrations than men for the same
      levels of adiposity. After controlling for gender and body fat, only fat mass
      (FM) expressed in kg, was significantly correlated with serum leptin
      concentration in men (partial rho = 0.811, p <0.001), whereas body mass index
      (BMI), hip circumference (HC), and FM expressed in kg, were significantly
      correlated with serum leptin concentration in women (partial rho = 0.214, p
      <0.001; partial rho = 0.201, p <0.01; and partial rho = 0.818, p <0.001,
      respectively). Percent body fat (PBF) was the only significant predictor of serum
      leptin concentration among men, explaining 42% of the variance in serum leptin
      concentration. In addition to PBF, waist circumference (WC) and HC were
      significant predictors of serum leptin concentration among women explaining 65%
      of the variance in serum leptin concentration. CONCLUSIONS: Serum leptin
      concentration is a function of adiposity as determined by PBF in both Mexican
      American men and women. HC and WC are associated with serum leptin concentration
      in Mexican-American women but not in men. BMI alone should not be used in
      evaluating the association of serum leptin concentration with body fatness in
      Mexican-Americans.

PMID- 17560465
TI  - To what extent does ozone therapy need a real biochemical control system?
      Assessment and importance of oxidative stress.
AB  - Ozone therapy is not officially allowed in many countries, but private medical
      services are using this therapy worldwide. However, appropriate control systems
      to assess the benefits and risks of systemic ozone therapy are not always used
      and in such cases the treatment is based on anecdotal reports. Oxidative stress
      phenomenon is becoming a highlighted biological process for ozone therapy because
      it is deeply involved in its mechanism of action. On the contrary, ozone therapy
      is an efficient regulator of the oxidative stress processes. In terms of
      therapeutic effects, it is convenient to know the metabolic status of the
      organism to face new oxidative challenges before and during ozone therapy
      applications. Oxidative stress is also important because it is involved as a
      cause or effect of many diseases. Since the 1990s, there has been the necessity
      of developing reliable systems for measuring oxidative stress in humans. In this
      sense, we have proposed a system for oxidative stress diagnosis that can serve as
      a control system for systemic ozone therapy applications. The system is based on
      the blood measurement of eight biomarkers (GSH, GPx, GST, SOD, CAT, DC, SRATB,
      and HPT) and the interpretation of these values by a computer-developed algorithm
      yielding four new indices (total antioxidant activity, total prooxidant activity,
      redox index and grade of oxidative stress). The system shows the patient's redox
      status and estimation of the oxidative stress level, with this information being
      relevant regarding implications on dosage and therapeutic effectiveness of ozone
      therapy.

PMID- 17560466
TI  - Value of symptoms to predict tilt testing outcome in patients with clinical
      suspicion of vasovagal syncope.
AB  - Studies to assess the value of clinical symptoms to predict the head-up tilt test
      (HUT) outcome in patients with suspicion of vasovagal syncope have shown
      controversial results. We undertook this study to compare the frequency of
      symptoms between subjects with and without history of syncope, its association
      with syncopal spells in those with a history of syncope and positive or negative
      HUT, and to identify clinical predictors of HUT outcome. Sixty seven subjects
      with a history of unexplained syncope and 26 subjects without a history of
      syncope were interviewed using a structured questionnaire before undergoing HUT,
      which was performed first in a passive phase and, if negative, was repeated with
      pharmacological challenge using 5 mg of sublingual isosorbide. Questionnaire
      included the 16 symptoms most frequently reported in previous studies. Only five
      symptoms were reported more frequently by subjects with history of syncope in
      comparison with subjects without it: visual blurring, dysesthesia, sighing
      dyspnea, tremor in fingers, and diaphoresis. Comparison of symptom frequency
      between patients with history of syncope and positive or negative HUT revealed
      that only two were significantly different: nausea and hot flashes. However, a
      detailed analysis of the data indicates that only hot flashes occurring just
      before the syncope were more common in those with a positive HUT. Although some
      symptoms were found more frequently in patients with a history of syncope than in
      those without it, the use of a structured questionnaire in the group of patients
      failed to predict the outcome of the HUT.

PMID- 17560467
TI  - Can ozonetherapy be performed if the biochemistry of the process cannot be
      controlled?

PMID- 17560468
TI  - Goiter and other iodine deficiency disorders: a systematic review of
      epidemiological studies to deconstruct the complex web.

PMID- 17560471
TI  - Early outcome of arthroscopic rotator cuff repair: a matched comparison with mini
      open rotator cuff repair.
AB  - PURPOSE: The purpose of this study was to compare the early functional outcome of
      mini-open and arthroscopic rotator cuff repair. METHODS: This was a retrospective
      study of 128 patients with chronic small- and medium-sized rotator cuff tears who
      underwent mini-open rotator cuff repair (MRCR) (n=63) or arthroscopic rotator
      cuff repair (ARCR) (n = 65). Data were collected prospectively at baseline 1 to 2
      weeks before surgery and at 3 and 6 months after surgery. Patients were
      identified from a prospectively created database based on the dimensions of the
      size of the tear as determined intraoperatively. Outcome was assessed via
      physical examination, visual analog scales (VASs), the Simple Shoulder Test, the
      Disabilities of the Arm, Shoulder and Hand questionnaire, and the Short Form 36
      (SF-36) Health Survey. Changes between baseline and follow-up were compared.
      RESULTS: All demographic variables and preoperative baseline parameters of the 2
      groups were equivalent. At 3 and 6 months, both MRCR and ARCR showed
      statistically significant improvement in all patient-derived outcome parameters
      (P < or = .0001) except for three SF-36 variables. The improvements in the SF-36
      bodily pain score at 3 months postoperatively (P = .041) and the VAS pain score
      at 6 months postoperatively (P = .03) were better for ARCR. All other
      improvements in patient-derived parameters were equivalent. CONCLUSIONS: In our
      retrospective study we found that the early functional outcomes of MRCR and ARCR
      of small- and medium-sized rotator cuff tears are nearly equivalent. In light of
      the purported advantages of ARCR that motivate its popularity, this is an
      unexpected finding. However, an equally important result of this study was the
      finding that ARCR was associated with statistically significant improvement in
      the 3-month SF-36 bodily pain score and 6-month VAS pain score (P = .041 and .03,
      respectively). LEVEL OF EVIDENCE: Level III, retrospective therapeutic
      comparative study.

PMID- 17560472
TI  - Arthroscopic versus open rotator interval closure: biomechanical evaluation of
      stability and motion.
AB  - PURPOSE: The purposes of this study were to investigate the differences between
      open and arthroscopic closure of the rotator interval (RI) on glenohumeral
      translation and range of motion. We also sought to determine if the addition of
      either an open or arthroscopic RI closure increases stability of the shoulder.
      METHODS: Fourteen fresh-frozen (10 paired) cadaveric shoulder specimens were
      mounted in a custom testing apparatus, and glenohumeral translation and rotation
      were obtained by using an optoelectric tracking system (Optotrak Certus; Northern
      Digital, Ontario, Canada). Specimens were randomly allocated to either open (n =
      7) or arthroscopic (n = 7) plication of the RI. The following were measured first
      with an intact and vented specimen and subsequently after an RI closure using
      either open or arthroscopic techniques: (1) range of motion in neutral and 90
      degrees abduction; (2) anterior and posterior translation at neutral rotation;
      (3) anterior translation at 90 degrees abduction with external rotation; and (4)
      posterior translation at 90 degrees flexion with internal rotation. RESULTS:
      Posterior stability was not improved from the intact state by either open (1.0-mm
      change) or arthroscopic (0.1-mm change) repair. The sulcus stability was improved
      in the open group (5.7 mm to 2.9 mm, P = .028), but not arthroscopically (5.1 to
      4.1 mm, P = .499). Neutral anterior stability was improved after open repair (7.2
      to 2.6 mm, P = .018), but not arthroscopically (2.3 to 2.4 mm, P = 0.5). However,
      anterior stability in external rotation (ER) at 90 degrees abduction was improved
      in the arthroscopic repair group (5.5 to 3.1 mm, P = .006). The mean loss of ER
      in neutral was greater in the open group (40.8 degrees) versus the arthroscopic
      group (24.4 degrees, P = .0038). The arthroscopic group showed an 11.7 degrees
      loss of ER in 90 degree abduction (P = .018) versus the open group loss of 4.8
      degrees. There were no significant differences in loss of IR in either neutral or
      90 degree abduction. CONCLUSIONS: Posterior stability was not improved by either
      open or arthroscopic rotator interval repair, and sulcus stability only improved
      with the open technique. Anterior stability in neutral was improved after open
      repair and in the arthroscopic repair group with the arm abducted. There was a
      large loss of external rotation with both techniques. CLINICAL RELEVANCE: This
      study suggests that arthroscopic RI closure adds little to the overall posterior
      and inferior stability of the shoulder joint, although anterior stability may be
      improved. There is a potentially large loss of external rotation after either
      repair method.

PMID- 17560473
TI  - Arthroscopic Bristow procedure for anterior instability in shoulders with a
      stretched or deficient capsule: the "belt-and-suspenders" operative technique and
      preliminary results.
AB  - PURPOSE: We report the results of a new technique consisting of a combined
      arthroscopic Bankart repair associated with a transfer of the coraco-biceps
      tendon to reinforce the deficient anterior capsule by lowering the subscapularis.
      METHODS: The procedure combines 2 parts: an arthroscopic Bankart repair, which
      recreates the glenoid concavity and retensions the inferior glenohumeral ligament
      (i.e., "the belt," or intra-articular ligamentoplasty), and an arthroscopic
      transfer of the conjoined tendon with a coracoid fragment, to reinforce the
      stretched or torn inferior glenohumeral ligament (i.e., "the suspenders," or
      extra-articular ligamentoplasty). The coracoid fragment is exteriorized, shaped,
      and calibrated, and a tenodesis of the coraco-biceps tendon is performed above
      the subscapularis tendon by fixing the coracoid fragment with a bioabsorbable
      interference screw in a glenoid socket in the scapular neck. Thirty-six patients
      were available for clinical and radiographic review with a minimum 1-year follow
      up. RESULTS: Of the patients, 28 (78%) were very satisfied, 5 (14%) were
      satisfied, and 3 (8%) were disappointed. In comparison to the contralateral
      shoulder, postoperative mobility revealed no loss of active anterior elevation, a
      mean deficit of 9 degrees in external rotation with the arm at the side, a mean
      deficit of 15 degrees in external rotation in abduction, and no loss of internal
      rotation. The mean Walch-Duplay score was 87 points. Failures occurred in 3
      patients (8%) who presented with recurrent instability. CONCLUSIONS: This new
      intra- and extra-articular combined technique constitutes an alternative in the
      treatment of anterior shoulder instability in patients with deficient or
      stretched anterior capsule. It combines the theoretic advantages of the Bristow
      bone-block procedure and the arthroscopic Bankart repair while eliminating the
      potential disadvantages of each. LEVEL OF EVIDENCE: Level IV, therapeutic case
      series.

PMID- 17560474
TI  - Anatomic reconstruction of the anterior cruciate ligament using double-bundle
      hamstring tendons: surgical techniques, clinical outcomes, and complications.
AB  - PURPOSE: The objective of the study was to retrospectively compare the clinical
      outcomes of anatomic double-bundle anterior cruciate ligament reconstruction via
      hamstring tendons with single-bundle reconstruction between April 2002 and March
      2004. METHODS: We retrospectively reviewed 123 consecutive patients, 71 of whom
      underwent double-bundle reconstruction and 52 of whom underwent single-bundle
      reconstruction. The same postoperative rehabilitation protocol was used for all
      patients. The patients were followed up for a mean of 33 months. We evaluated
      manual knee laxity, anterior knee laxity as measured with the KT1000 arthrometer
      (MEDmetric, San Diego, CA), range of knee motion, isokinetic peak torque of knee
      extension and flexion strength adjusted for body weight as determined by Cybex
      testing (Lumex, Ronkonkoma, NY), and Lysholm score. RESULTS: The Lachman test was
      negative in 64 cases (90%) and the pivot-shift test was negative in 62 cases
      (87%) in the double-bundle group. The Lachman test was negative in 45 cases (86%)
      and the pivot-shift test was negative in 42 cases (81%) in the single-bundle
      group. There was an extension deficit of greater than 5 degrees in 19 cases (26%)
      in the double-bundle group and 6 cases (10%) in the single-bundle group (P <
      .05). The side-to-side difference in anterior tibial translation measured with
      the KT1000 arthrometer was 1.7 +/- 2.0 mm in the double-bundle group and 1.9 +/-
      2.2 mm in the single-bundle group. The isokinetic peak torque of knee extension
      and flexion strength was 90% and 89%, respectively, in the double-bundle group
      and 87% and 86%, respectively, in the single-bundle group. The Lysholm score
      averaged 96.8 +/- 5.1 in the double-bundle group and 92.8 +/- 6.9 in the single
      bundle group postoperatively. CONCLUSIONS: No significant difference was found
      between the 2 procedures with regard to manual knee laxity, anterior knee laxity
      measured by the KT1000 arthrometer, knee extension and flexion strength, and
      Lysholm score. In contrast, there was a significant difference in the range of
      knee motion between the 2 groups. The findings of our study do not support the
      routine adoption of double-bundle reconstruction. LEVEL OF EVIDENCE: Level III,
      retrospective comparative study.

PMID- 17560475
TI  - Intra-articular injection of mesenchymal stromal cells in partially torn anterior
      cruciate ligaments in a rat model.
AB  - PURPOSE: The purpose of this study was to biomechanically and histologically
      evaluate whether intra-articularly injected mesenchymal stromal cells can
      accelerate the healing of a partially torn anterior cruciate ligament (ACL).
      METHODS: Ninety-eight 12-week-old male Sprague-Dawley rats were studied. The
      right ACL was partially transected, and a sham operation was performed on the
      left knee. Mesenchymal stromal cells obtained from bone marrow of green
      fluorescent protein (GFP) transgenic Sprague-Dawley rats were cultured for 2
      weeks in medium. In the MSC(+) group, 1 x 10(6) cells were suspended in phosphate
      buffered saline solution and were injected into the right knee with the partially
      transected ACL. In the MSC(-) group, only phosphate-buffered saline solution was
      injected. Six animals from each group were evaluated histologically at 1, 2, 3,
      and 4 weeks after surgery, and they were evaluated biomechanically immediately
      after surgery (time zero) (n = 9) and also at 2 weeks (n = 11) and 4 weeks (n =
      12) after surgery in both groups. For biomechanical testing, the ultimate failure
      load of a prepared femur-ACL-tibia complex was measured. We then compared the
      transected side with the sham side in each group. GFP luminescence was observed
      with a fluorescence microscope to detect whether the injected cells mobilized
      into the covered tissue. RESULTS: In the MSC(-) group the transected area
      retracted with increasing time, and the gap remained void of any tissues at all
      time points after surgery. In the MSC(+) group at 2 and 4 weeks after surgery,
      the transected area was covered with healing tissues in which GFP-positive cells
      were detected. Furthermore, the histologic score of the MSC(+) group was
      significantly better than that of the MSC(-) group. The ultimate failure load of
      the femur-ACL-tibia complex in the MSC(+) group was significantly higher than
      that in the MSC(-) group at 4 weeks after surgery. CONCLUSIONS: We conclude from
      our histologic and biomechanical measurements that injected mesenchymal stromal
      cells can accelerate the healing of partially torn ACLs. CLINICAL RELEVANCE: The
      intra-articular injection of mesenchymal stromal cells can be a viable option for
      treating partially torn knee ACLs.

PMID- 17560476
TI  - A prospective randomized study of 4-strand semitendinosus tendon anterior
      cruciate ligament reconstruction comparing single-bundle and double-bundle
      techniques.
AB  - PURPOSE: A randomized clinical study was conducted to compare the outcome between
      double-bundle (DB) and single-bundle (SB) anterior cruciate ligament (ACL)
      reconstructions with 4-strand semitendinosus tendon (ST). METHODS: We divided 68
      patients with unilateral ACL injury into 2 groups according to their birth date,
      and they were followed up in person for a mean of 25 months (range, 18 to 41
      months). Each group of 34 patients underwent either DB or SB ACL reconstruction
      using 4-strand ST with EndoButton femoral fixation (Smith & Nephew Endoscopy,
      Andover, MA) and anchor staple tibial fixation. There was no difference between
      the 2 groups with regard to age at surgery, sex, follow-up period, period before
      surgery, combined meniscus injuries, and athletic activity level. All patients
      followed the same postoperative program. They were evaluated using manual knee
      laxity tests, instrumented anterior laxity measurements (KT-1000 arthrometer
      [MEDmetric, San Diego, CA]), knee extension and flexion strength testing, and so
      on. General knee condition was evaluated by use of the Lysholm knee score and
      subjective rating scale. RESULTS: There were no significant differences between
      the 2 groups with regard to range of motion, thigh girth, muscle strength, and
      Lysholm score. Manual knee laxity testing revealed that negative Lachman and
      pivot-shift test results were found in more patients in the DB group than in the
      SB group. KT measurements averaged 2.4 mm in the SB group and 1.4 mm in the DB
      group, which was statistically significantly different. Statistical analysis
      showed no significant difference regarding all of the modified International Knee
      Documentation Committee-categorized data between the 2 groups. CONCLUSIONS: This
      randomized controlled trial indicated that DB ACL reconstruction via 4-strand ST
      is superior to the SB technique with regard to anterior and rotational stability;
      however, it fails to show any subjective difference. LEVEL OF EVIDENCE: Level I,
      prospective randomized controlled clinical study.

PMID- 17560477
TI  - Anterior cruciate ligament reconstruction after 10 to 15 years: association
      between meniscectomy and osteoarthrosis.
AB  - PURPOSE: To evaluate the stability and arthrosis of the knee 10 to 15 years after
      arthroscopic-assisted anterior cruciate ligament (ACL) reconstruction with
      patellar tendon graft. METHODS: From July 1986 to March 1991, 82 patients
      underwent arthroscopic-assisted ACL reconstruction with patellar tendon graft. Of
      these, 62 returned for follow-up evaluation between November 2000 and April 2001.
      Four different physicians, blinded to each other's examination findings,
      evaluated the radiologic as well as surgical results according to the
      International Knee Documentation Committee criteria and the Lysholm knee scoring
      scale. RESULTS: There were 47 male and 15 female patients. The mean period
      between injury and surgery was 16 months (range, 2 weeks to 8 years). Results of
      radiographs were compared with the finding of meniscal lesions during surgery and
      with International Knee Documentation Committee test results. A statistically
      significant association (P < .0001) was found between medial or lateral arthrosis
      of the knee and meniscal injury. In all patients the presence of tears in both
      menisci was associated with osteoarthrosis in both compartments (medial and
      lateral). CONCLUSIONS: In patients who underwent arthroscopic-assisted ACL
      reconstruction with patellar tendon graft who also had medial or lateral
      meniscectomy (or both), arthrosis of the respective compartments developed by 10
      to 15 years after reconstruction. Meniscectomy was also associated with poorer
      results on objective tests of knee function, even with a stable knee joint. LEVEL
      OF EVIDENCE: Level IV, therapeutic case series.

PMID- 17560478
TI  - Collagenous fibril texture of the discoid lateral meniscus.
AB  - PURPOSE: To provide the theoretic basis for treatment and to increase the
      understanding of the tear patterns of the discoid meniscus, we observed the
      collagen orientation of the discoid meniscus. METHODS: Ten meniscus specimens
      were used to observe the collagen fibril orientation of the complete type of the
      discoid lateral menisci. The samples were observed layer by layer under a
      polarizing filter microscope by using Sirius red staining, and they were also
      observed under a scanning electron microscope. RESULTS: The lateral discoid
      meniscus is classified into 7 layers based on collagen fibril orientation. The
      femoral surface of the discoid meniscus is covered by dense and well-arranged
      thick fibrils, which very much resembles a bunched streak. The fibrils show a
      sagittal isotropic-arranged orientation. However, the tibial surface shows an
      irregular and anisotropically arranged orientation. In the outer layer, a
      meshwork of thin fibrils has been observed. The collagen fibrils in the inner
      layer are radially orientated from the lateral side to the medial side. In the
      central layer, the peripheral collagen fibrils are displayed as dense bundles
      running in a circumferential pattern, whereas its medial zone shows as thin,
      loosely, and irregularly arranged fibrils without a bundle formation. The
      anterior and posterior zones of the central layer show the collagen fibrils with
      a straight arrangement in the radial direction. CONCLUSIONS: In the lateral
      middle zone of discoid meniscus, the collagen fibrils run parallel to the
      periphery of the meniscus. Therefore, it would be ideally suited for resisting
      hoop stresses. From this anatomic study, it is apparent that the peripheral
      portion of the meniscus is constructed to bear a load. CLINICAL RELEVANCE: It is
      strongly recommended that the peripheral portion of the discoid meniscus should
      be preserved when a resection of the meniscus is mandatory.

PMID- 17560479
TI  - Risk to the lateral geniculate artery during arthroscopic lateral meniscal suture
      passage.
AB  - PURPOSE: The purpose of this study was to evaluate the risk of lateral geniculate
      artery injury during suture passage through the lateral meniscus. METHODS:
      Sutures were passed via inside-out and outside-in techniques in 11 embalmed
      cadaveric knees. The number of punctures of the lateral geniculate artery and
      quantitative distances of needle penetrations were measured. RESULTS: The lateral
      geniculate artery was punctured 7 times during inside-out passes through the
      junction of the middle and anterior third of the meniscus and 8 times during
      passes through the body of the middle third of the meniscus. During outside-in
      passes, there were 5 punctures when passing anterior to the lateral collateral
      ligament and 4 punctures when posterior to the ligament. CONCLUSIONS: The lateral
      geniculate artery is in close proximity to the lateral meniscus and is punctured
      often during in vitro inside-out meniscal repair in the embalmed cadaver model.
      CLINICAL RELEVANCE: Methods of meniscal repair that do not violate the lateral
      geniculate artery may offer improved rates of healing and should be further
      evaluated.

PMID- 17560480
TI  - Sequential changes in implanted cartilage after autologous osteochondral
      transplantation: postoperative acoustic properties up to 1 year in an in vivo
      rabbit model.
AB  - PURPOSE: For successful autologous osteochondral transplantation, it is important
      that the cartilage in an implanted plug provide histologic replacement of damaged
      cartilage with cartilage that is structurally and mechanically normal. The
      purpose of this study was to investigate whether the press-fit technique
      reconstructs the normal hyaline cartilage and provides acoustic stiffness equal
      to that of normal intact cartilage. METHODS: In 36 rabbits an osteochondral plug,
      6 mm in diameter, was removed from the right patellar groove and grafted into a
      recipient hole, 5 mm in diameter, in the left patellar groove. Specimens at 2, 4,
      8, 12, 24, and 52 weeks postoperatively were assessed by macroscopic and
      histologic observation and by use of an ultrasonic system. The ultrasonic
      acoustic stiffness, acoustic surface irregularity, and acoustic thickness of the
      implanted cartilage were examined and compared with normal intact cartilage.
      RESULTS: The gross appearance of the implanted cartilage was glossy, maintained
      good surface smoothness, and survived well throughout the observation period. The
      cartilage recovered histologic features of hyaline cartilage. The acoustic
      stiffness decreased up to 12 weeks and then increased at 24 and 52 weeks after
      surgery. The acoustic stiffness at 8 or 12 weeks was significantly lower
      (acoustically softer) than that of control cartilage (P < .001). The acoustic
      stiffness at 52 weeks was equal to that of the control. The difference in
      acoustic surface irregularity was not significant. The acoustic thickness at 8
      weeks was higher (acoustically thicker) than that of the control (P < .01).
      CONCLUSIONS: Although the reason acoustically soft cartilage in plugs becomes
      acoustically stiff and whether the histology of the implanted cartilage had
      recovered completely remain unclear, the acoustic stiffness recovered to normal
      control values by 52 weeks postoperatively. CLINICAL RELEVANCE: Postoperative
      care for up to 12 weeks should be taken after autologous osteochondral
      transplantation.

PMID- 17560481
TI  - The properties of damaged and undamaged suture used in metal and bioabsorbable
      anchors: an in vitro study.
AB  - PURPOSE: The purpose of this study was to determine the mechanical properties of
      undamaged and damaged sutures in metal and bioabsorbable suture anchors. METHODS:
      Undamaged and damaged FiberWire (Arthrex, Naples, FL), Tevdek (Deknatel,
      Mansfield, MA), and PDS (Ethicon, Somerville, NJ) sutures were tested by a single
      pull to failure while being pulled parallel to the axis of either a metal or
      bioabsorbable suture anchor. Sutures were damaged by use of a razor blade
      incorporated into a custom-designed jig. The friction of the sutures through the
      anchor eyelets was also tested. RESULTS: For both anchor types, FiberWire was the
      strongest suture studied. Undamaged PDS had a significantly greater load to
      failure than Tevdek. Although all sutures lost significant strength when damaged,
      PDS lost the most, with damaged PDS becoming significantly weaker than damaged
      Tevdek. Damaged FiberWire was significantly stronger in metal anchors compared
      with bioabsorbable anchors, with failure of the bioabsorbable suture eyelet
      preventing testing of undamaged FiberWire. Neither undamaged nor damaged PDS or
      Tevdek had a significant difference in strength between metal and bioabsorbable
      anchors. However, in metal anchors the mechanical properties of undamaged Tevdek
      were inferior to those of the other undamaged sutures tested. For undamaged or
      damaged sutures through either anchor type, PDS suture had the highest
      coefficient of friction, significantly higher than FiberWire and Tevdek. All
      sutures, undamaged or damaged, had significantly less friction in bioabsorbable
      anchors compared with metal anchors. CONCLUSIONS: The FiberWire-anchor construct
      is significantly weaker when bioabsorbable anchors are used instead of metal
      anchors. For Tevdek and PDS sutures, the anchor type does not affect the strength
      of the construct, as the suture is the limiting factor. When used with suture
      anchors, PDS has the most friction of the sutures tested, potentially leading to
      suture damage, which disproportionately weakens PDS compared with the other
      sutures tested. For both undamaged and damaged sutures, bioabsorbable anchors
      lead to less friction than do metal anchors, which may lessen suture damage in
      vivo. CLINICAL RELEVANCE: The mechanical properties of damaged suture are
      important to all surgeons who use suture arthroscopically.

PMID- 17560482
TI  - Arthroscopic rotator cuff repairs: an anatomic and biomechanical rationale for
      different suture-anchor repair configurations.
AB  - The goal of rotator cuff repairs is to achieve high initial fixation strength,
      minimize gap formation, maintain mechanical stability under cyclic loading, and
      optimize the biology of the tendon-bone interface until the cuff heals
      biologically to the bone. We have seen an evolution in our approaches to fixing
      rotator cuff tears from open to mini-open to all arthroscopic. In our
      arthroscopic techniques, we have also seen a change in the types of anchors and
      sutures we use and our repair techniques including an evolution in techniques
      that include single row, double row, and, most recently, transosseous equivalent
      fixation. Single-row repairs are least successful in restoring the footprint of
      the rotator cuff and are most susceptible to gap formation. Double-row repairs
      have an improved load to failure and minimal gap formation. Transosseous
      equivalent repairs have the highest ultimate load and resistance to shear and
      rotational forces and the lowest gap formation. This review will discuss the
      anatomy and biomechanics of a normal rotator cuff, the biomechanical factors that
      play a role in rotator cuff repairs, the initial fixation repair mechanics, and
      finally propose an algorithm for rotator cuff fixation based on tissue quality
      and tear configuration.

PMID- 17560483
TI  - Clinical evidence shows no difference between single- and double-row repair for
      rotator cuff tears.
AB  - Tears of the rotator cuff may be repaired by single- or double-row techniques.
      Single-row methods do not restore the rotator cuff footprint but do provide a
      good functional outcome. We surveyed the literature to ascertain the origin of
      the current trend of using double-row methods of repair. The footprint repair is
      a benefit of double-row fixation with strong evidence of its biomechanical
      success. However, the functional outcome of double-row fixation is equivalent to
      single-row fixation. Given the lack of scientific evidence and despite the
      enthusiasm of surgeons for this new technique, single-row fixation remains an
      acceptable method for managing these injuries, and it is our opinion that it is
      the preferable method.

PMID- 17560484
TI  - Arthroscopic stabilization of Neer type 2 fracture of the distal part of the
      clavicle.
AB  - With regard to the anatomic basis of Neer type 2 fractures of the distal part of
      the clavicle, a clavicle fracture is associated with a coracoclavicular conoid
      ligament disruption. We describe an arthroscopic-assisted surgical procedure to
      stabilize the fracture and reconstruct the ligament. Surgery is performed with
      the patient in the beach-chair position. Through a 2-cm incision perpendicular to
      the direction of the fracture, we perform suturing around the fracture. During
      the arthroscopic procedure, the coracoid process is exposed by opening the
      rotator interval and the medial part of the capsule. The knee of the coracoid
      process should be exposed via an anterolateral portal for the arthroscope. Then,
      by use of an acromioclavicular joint stabilization device from Arthrex (Naples,
      FL), a hole is placed through the knee of the coracoid process. FiberTape suture
      (Arthrex) is passed around the clavicle and through the knee of the coracoid
      process. The intra-articular sutures are pulled out through the upper incision on
      top of the clavicle. Tightening of the 2 knots is performed at the same time.
      This arthroscopic-assisted surgery allows for total recovery of shoulder
      function, without the inconvenience of device migration or acromioclavicular
      joint lesions reported with other procedures.

PMID- 17560485
TI  - The double-pulley technique for double-row rotator cuff repair.
AB  - In an effort to maximize the area of footprint coverage, we developed the "double
      pulley technique" for double-row rotator cuff repairs. Two suture anchors are
      inserted at the articular margin of the greater tuberosity (one anterior and one
      posterior). All 4 suture strands from each anchor are passed through a single
      medial point on the torn cuff. In this way, the 4 suture strands from the
      anteromedial anchor pass through 1 point in the cuff and the 4 strands from the
      posteromedial anchor pass through a different point in the cuff. A suture strand
      from 1 anchor is tied extracorporeally to a suture strand of the same color from
      the other anchor. The other ends of those 2 strands are then pulled, thereby
      delivering this extracorporeal knot into the joint and over the medial footprint.
      These 2 free suture strands are then tied together as a static knot. The
      procedure is repeated with the other sutures. This technique creates a double
      mattress suture medially, which compresses the intervening tendon bridge against
      its bone bed. We call this procedure the double-pulley technique because it uses
      the anchor eyelets as pulleys to deliver the extracorporeal knot into the
      shoulder. After the lateral row repair is performed, the rotator cuff footprint
      will be completely reconstituted.

PMID- 17560486
TI  - Acute arthroscopic removal of a bullet from the shoulder.
AB  - Arthroscopic procedures are frequently used for extraction of foreign bodies such
      as bullets from joints. Retained bullets have some effects as loose bodies that
      cause mechanical symptoms and destroy articular cartilage. Bullets and lead
      particles in synovial fluid dissolve in time and cause periarticular fibrosis,
      chondrolysis, hypertrophic arthropathy, and sometimes chronic lead intoxication.
      A 21-year-old man was treated after he sustained a gunshot wound to his left
      shoulder. Shoulder arthroscopy was performed through the standard posterior
      portal. The bullet was observed in the posterior recess and was removed by means
      of a 10-mm cannula placed anteriorly. The use of arthroscopy for removal of the
      bullet from the shoulder joint of this patient minimized surgical dissection and
      blood loss and reduced the likelihood of complications. The patient was free of
      symptoms within 1 month. Given the disadvantages of traditional techniques such
      as heavy blood loss, large incisions, high risk for neurovascular anatomic
      structures, poor visualization of articular surfaces, and prolonged recovery
      times, we recommend arthroscopic removal of foreign bodies from the shoulder
      joint as an excellent choice for the treatment of patients with such intra
      articular injuries.

PMID- 17560487
TI  - Arthroscopic autologous bone graft with arthroscopic Bankart repair for a large
      bony defect lesion caused by recurrent shoulder dislocation.
AB  - Many clinicians believe that a large bony defect of the glenoid must be treated
      with bone grafting when a Bankart procedure is performed. Various types of bone
      graft, such as open bone graft, Eden-Hybinnette, J-bone graft, coracoid transfer,
      and Latarjet, have been used. These require open procedures that are difficult to
      perform arthroscopically. We performed an arthroscopic autologous bone graft and
      an arthroscopic Bankart repair at the same time to treat a patient with recurrent
      dislocation of the shoulder joint and a large bony Bankart lesion. We harvested
      from the lateral site of the acromion 2 bones that were 2.7 mm in cylindrical
      diameter. We transplanted these bones to the large bony defect of the
      anteroinferior area of the glenoid and placed anchors between the 2 plugs. During
      the 30 months since the surgery was performed, the patient has not experienced
      dislocation or apprehension about the shoulder. A 3-dimensional computed
      tomography scan showed enlargement of the glenoid surface. Our surgical procedure
      offers promise for treatment of patients with recurrent dislocation of the
      shoulder joint and a large bony Bankart lesion because it allows the surgeon to
      alter the size and the grafted site of the cylindrical bone according to the size
      of the defect.

PMID- 17560488
TI  - Endoscopically assisted excision of digital enchondroma.
AB  - We present 2 cases of endoscopically assisted curettage of enchondroma of the
      hand. After initial open curettage of the lesion, a 1.9-mm arthroscope was
      introduced through a small cortical window. Under arthroscopic guidance, residual
      pathologic material was freed from the cavity wall and evacuated with the aid of
      repeated saline lavage combined with suction. The saline was injected through an
      18-gauge angiocatheter under direct endoscopic control. The endoscope was then
      used to observe the filling of the cavity with demineralized bone matrix (DBX;
      Synthes [USA], Paoli, PA). We believe that endoscopically assisted curettage
      presents several advantages over open curettage alone. First, direct
      visualization of the medullary canal permits accurate assessment of the extent of
      the enchondroma. Second, the endoscope permits accurate assessment of the
      adequacy of the curettage, thus avoiding the need to perform multiple, blind, and
      aggressive passes with a curette. Multiple passes can increase the risk of
      violation of the cortical shell and can prolong the procedure. Third, the ability
      to completely clear the medullary canal of all tumors should logically reduce the
      rate of recurrence. In conclusion, the addition of an endoscope is an inexpensive
      modification that promises to save time, decrease morbidity, and possibly improve
      long-term outcomes.

PMID- 17560489
TI  - Dreams of the future, remembering the past.

PMID- 17560490
TI  - Hip arthroscopy: an emerging gold standard.

PMID- 17560492
TI  - Reinventing the wheel.

PMID- 17560493
TI  - About "Arthroscopic Bankart repair ...".

PMID- 17560495
TI  - Antiepileptic drugs and visual function.
AB  - Antiepileptic drugs are known to result in visual disturbances. A number of
      antiepileptic drugs have recently been reported to result in various
      abnormalities of vision, particularly deficiencies in visual fields and color
      vision. Moreover, there has been a marked improvement in the diagnosis and
      understanding of the pathophysiology of visual disturbance. This review collects
      evidence for visual adverse effects induced by the older antiepileptic drugs
      (barbiturates, benzodiazepine, carbamazepine, valproic acid, ethosuximide, and
      phenytoin) and the newer ones (vigabatrin, topiramate, tiagabine, levetiracetam,
      lamotrigine, gabapentin, felbamate, and oxcarbazepine).

PMID- 17560496
TI  - Elevation of tumor necrosis factor-alpha in cerebrospinal fluid of autistic
      children.
AB  - Recent reports implicating elevated cytokines in the central nervous system in a
      small number of patients studied with autism have reported clinical regression.
      These studies have not focused on tumor necrosis factor-alpha as a possible
      marker for inflammatory damage. A series of 10 children with autism had clinical
      evaluation of their serum and spinal fluid for inflammatory changes and possible
      metabolic disease as part of their neurological evaluation. Elevation of
      cerebrospinal fluid levels of tumor necrosis factor-alpha was significantly
      higher (mean = 104.10 pg/mL) than concurrent serum levels (mean = 2.78 pg/mL) in
      all of the patients studied. The ratio of the cerebrospinal fluid levels to serum
      levels averaged 53.7:1. This ratio is significantly higher than the elevations
      reported for other pathological states for which cerebrospinal fluid and serum
      tumor necrosis factor-alpha levels have been simultaneously measured. This
      observation may offer a unique insight into central nervous system inflammatory
      mechanisms that may contribute to the onset of autism and may serve as a
      potential clinical marker. More controlled study of this potentially important
      observation may prove valuable.

PMID- 17560497
TI  - Efficacy of intravenous midazolam for status epilepticus in childhood.
AB  - A retrospective multicenter study was conducted, designed to evaluate the
      efficacy and safety of midazolam for the treatment of status epilepticus. The
      subjects were 358 inpatients who received intravenous midazolam therapy for
      status epilepticus. The mean age was 48.6 +/- 46.5 months. The underlying
      disorder was epilepsy in 195 cases, and acute symptomatic diseases in 163
      (encephalitis or encephalopathy in 88 cases). Midazolam was administered as a
      bolus dose (0.25 +/- 0.21 mg/kg), followed if necessary by continuous infusion
      (0.26 +/- 0.25 mg/kg/hr). The bolus injection was effective in 162 (56.6%) of the
      286 cases. In the end, seizure suppression was obtained in 231 cases (64.5% of
      the total). The effectiveness of midazolam was lower in patients in whom
      midazolam was initiated more than 3 hours after seizure onset, and this tendency
      was particularly marked in the epilepsy group. During the treatment period, 10
      patients died, but none of these deaths were associated with midazolam therapy.
      The incidence and types of adverse events were consistent with previously
      reported data. The present results indicate that midazolam is highly effective
      for the management of status epilepticus, if used sufficiently early after
      seizure onset.

PMID- 17560498
TI  - The role of neuropsychologic tests in the diagnosis of attention deficit
      hyperactivity disorder.
AB  - Attention, memory, executive function, language, and visual-motor skills were
      evaluated in a sample of 621 children, 6 to 11 years old, to assess the
      discriminant validity of neuropsychologic testing. Attention deficit
      hyperactivity disorder cases (249) and controls (372) were identified and tested.
      Analysis of covariance, nonparametric comparison tests, effect sizes,
      discriminant function, factor analyses, and receiver-operator characteristics
      curve analyses were used to establish the best diagnostic cutoff points for each
      variable. Statistically significant differences were found on cognitive effort,
      auditory skills, continuous performance test, working memory, visual-motor
      skills, verbal comprehension, and executive function measures (P < 0.05);
      however, the effect of group sizes was low to modest (0.24 to 0.54). Receiver
      operator characteristics curve analysis showed modest sensitivity and low
      specificity, demonstrating that an important proportion of the variance in test
      scores was overlapping. Factor analysis of neuropsychologic testing results
      revealed a structure of six factors each for attention deficit hyperactivity
      disorder, control, and combined samples. The latent variables produced one
      discriminant function with a total correct classification accuracy of 61.9%.
      Neuropsychologic tests should be used as Attention Deficit Hyperactivity Disorder
      diagnostic tools with caution, but they hold promise for identifying core
      cognitive deficits and processes that can aid prevention and intervention.

PMID- 17560499
TI  - Infantile onset of hereditary spastic paraplegia poorly predicts the genotype.
AB  - Age of symptom onset of hereditary spastic paraplegia varies from infancy to the
      eighth decade. Infantile onset of hereditary spastic paraplegia without a
      positive family history may cause difficulties in reaching the correct diagnosis
      and misdiagnosis as a diplegic form of cerebral palsy is particularly common.
      Infantile onset of hereditary spastic paraplegia caused by mutations in the
      spastin gene (SPAST) is very rare and previously was mostly associated with
      codominant mutations in this gene. We present a kindred with infantile onset of
      spastic paraplegia in three successive generations caused by confirmed de novo
      novel mutation 1537G>A (G471D) in SPAST. Several family members were previously
      diagnosed as having cerebral palsy. Infantile onset of hereditary spastic
      paraplegia may be caused by mutations in multiple genes, and this phenotype does
      not reliably predict the genotype. Pediatric neurologists need to be aware of
      relatively frequent de novo mutations in hereditary spastic paraplegia genes and
      a possibility that this condition presents in infancy without a positive family
      history.

PMID- 17560500
TI  - Clinical analysis of childhood occipital lobe epilepsy in 43 Taiwanese patients.
AB  - Occipital lobe epilepsy in children can present as an idiopathic form (i.e.,
      childhood epilepsy with occipital paroxysms) or as a symptomatic form. Forty
      three children (18 boys, 25 girls) were divided into the idiopathic group or
      symptomatic group, according to the classification for epileptic seizures of the
      International League Against Epilepsy. Patients in the idiopathic group were
      further subdivided into the Panayiotopoulos or Gastaut type, according to
      clinical presentation. The idiopathic group consisted of 15 children (5 boys, 10
      girls), of whom 11 were of the Panayiotopoulos type and 4 of the Gastaut type.
      The symptomatic group consisted of 28 children (13 boys, 15 girls). The average
      age of seizure onset in the idiopathic group was younger than in the symptomatic
      group (6.5 +/- 2.4 vs 8.5 +/- 3.0 years). Ictal vomiting was more common in the
      idiopathic group, and positive visual symptoms were more common in the
      symptomatic group. Mean epilepsy duration in the idiopathic group was shorter
      (5.7 +/- 5.3 vs 20.1 +/- 16.0 months), and the response to treatment was better.
      The average age of seizure onset was much younger in the Panayiotopoulos than in
      the Gastaut type (5.4 +/- 1.5 vs 9.5 +/- 1.5 years), and mean epilepsy duration
      was also shorter (3.9 +/- 4.2 vs 10.5 +/- 4.9 months). Seizure semiology can
      distinguish between idiopathic occipital lobe epilepsy and the symptomatic form
      with ictal vomiting and positive visual symptoms. In idiopathic occipital lobe
      epilepsy, the Panayiotopoulos type has better prognosis than the Gastaut type.

PMID- 17560501
TI  - The spectrum of polyneuropathies in childhood detected with electromyography.
AB  - Only a few studies have been reported describing polyneuropathies in a series of
      children. To study the clinical and neurophysiological spectrum of
      polyneuropathies in a large series of children and obtain an overview of their
      etiologies, this retrospective study reevaluated all electromyograms and
      electrophysiologic studies performed between 1995 and 2004 in children under 17
      years of age at the Radboud University Nijmegen Medical Center, a tertiary
      neuromuscular reference center. Electromyograms revealing polyneuropathy were
      selected for further analysis (n = 118), and the medical records were reviewed to
      supplement electromyographic findings with the clinical diagnosis. Hereditary
      polyneuropathies made up 68% of the total, and 54% of these were isolated
      polyneuropathies; in the remaining 46%, polyneuropathy was part of a more complex
      disorder. The acquired polyneuropathies were primarily inflammatory. Nerve
      biopsies had been performed in 22 of the 118 cases (19%) and led to a diagnosis
      in 4 cases. Despite sophisticated investigation, 11 cases (9%) remained
      unclassified for underlying cause. Hereditary motor and sensory neuropathies are
      the most common type of polyneuropathy in childhood, followed by polyneuropathies
      as part of an inborn error of metabolism and inflammatory polyneuropathies (in
      patients in whom electromyography was used to diagnose the neuropathy). In the
      full series of patients, nerve biopsy did not play a prominent role in the
      diagnostic work-up of childhood polyneuropathies, due to the increasing
      availability of other laboratory (genetic and metabolic) diagnostic tools. Nerve
      biopsy nonetheless proved to have an important diagnostic yield in selected,
      complex cases.

PMID- 17560502
TI  - ARSA gene mutations in five Chinese metachromatic leukodystrophy patients.
AB  - The objective was to identify arylsulfatase A mutations, if any, in five Chinese
      patients with metachromatic leukodystrophy. This would be the first such study in
      China. All eight exons and exon-intron boundaries of the arylsulfatase A gene
      (ARSA) were amplified with polymerase chain reaction, which was followed by
      direct DNA sequencing. Patient 1 exhibited a homozygous mutation at c.954G>A
      (p.W318X) in exon 5. Patient 2 exhibited compound heterozygous mutations,
      identified as one allele with the c.862C>T (p.R288C) missense mutation in exon 5
      and the other allele with the c.1338dupC frameshift mutation in exon 8. Patient 3
      exhibited only a c.179_180dupCA frameshift mutation in exon 1 in one allele.
      Patients 4 and 5 exhibited identical compound heterozygous mutations, identified
      as one allele with the c.296G>T (p.G99V) missense mutation and the other allele
      with the c.251G>A (p.R84Q) missense mutation in exon 2. Six DNA variants of the
      arylsulfatase A gene were identified: two novel frameshift mutations
      (c.179_180dupCA and c.1338dupC), one known nonsense mutation (p.W318X), and three
      known missense mutations (p.R84Q, p.G99V, and p.R288C).

PMID- 17560503
TI  - PHACE syndrome with intracerebral hemangiomas, heterotopia, and endocrine
      dysfunction.
AB  - PHACE is an acronym to describe the association of posterior fossa brain
      malformations, hemangiomas, arterial anomalies, coarctation of the aorta, cardiac
      defects, and eye abnormalities. More than 200 cases have been reported. The
      present report presents the cases of two female infants with PHACE syndrome, both
      of whom had additional congenital defects of subependymal gray matter
      heterotopia, craniofacial arterial anomalies, and pituitary dysfunction. One had
      an extensive segmental facial hemangioma with ipsilateral intracranial
      hemangiomas. The other had multiple cutaneous hemangiomas, but no segmental
      facial hemangioma. These two cases suggest a further expansion of the spectrum of
      PHACE to include other forms of disordered cerebral development and endocrine
      dysfunction.

PMID- 17560504
TI  - Bilateral periventricular nodular heterotopia with amniotic band syndrome.
AB  - The amniotic (constriction) band syndrome is characterized by distal ring
      constrictions, intrauterine amputations, and acrosyndactyly. External
      constriction by amniotic bands is the generally accepted mechanism: early
      amniotic rupture leads to formation of mesodermal fibrous strands that constrict,
      entangle, and amputate distal portions of limbs. Etiology is heterogeneous.
      Anecdotal cases involving central nervous system abnormalities (e.g., acrania,
      anencephaly, polymicrogyria, congenital bilateral perisylvian syndrome, neuronal
      heterotopia, septo-optic dysplasia, and spinal cord tethering) have been
      reported. We describe a 9-year-old girl with typical features of constriction
      band syndrome localized to the lower limbs who had also profound mental
      retardation and drug-resistant epilepsy associated with bilateral periventricular
      nodular heterotopia (a brain malformation of neuronal migration and proliferation
      caused by mutations in the X-linked filamin 1 gene [FLN1] on chromosome Xq28).
      The karyotype was normal, as was mutational screening for FLN1. The occurrence of
      bilateral periventricular nodular heterotopia in the context of amniotic band
      syndrome is novel (chance occurrence of both: 0.000004%).

PMID- 17560505
TI  - A novel mutation of the CLN8 gene: is there a Mediterranean phenotype?
AB  - We report the first known case in Israel of a patient with an early childhood
      onset of ceroid-lipofuscinosis who is homozygous to a mutation of the CLN8 gene.
      This patient further expands the clinical varieties of CLN8, initially reported
      in Finland and Turkey and recently in Italy. The ultrastructural pathology of a
      skin biopsy specimen revealed abundant typical fingerprint profiles, but rare
      granular osmiophilic bodies and curvilinear structures. Sequencing of exon 3 of
      the CLN8 gene revealed a novel C>G missense mutation at a conserved amino acid
      glutamine 256 to glutamic acid. Our findings further raise the possibility of the
      existence of a Mediterranean CLN8 variant.

PMID- 17560506
TI  - Elevated thyroid peroxidase antibodies with encephalopathy in MELAS syndrome.
AB  - Both the syndrome of mitochondrial encephalomyopathy, lactic acidosis, and stroke
      like episodes (MELAS syndrome) and Hashimoto's encephalopathy can present with
      nonspecific encephalopathy. Hashimoto's encephalopathy is an association of
      steroid-responsive encephalopathy with elevated thyroid peroxidase antibodies.
      Steroid-responsive encephalopathy, however, is not characteristic of the MELAS
      syndrome, which typically presents with stroke-like episodes and lactic acidosis
      in cerebrospinal fluid and blood. Here, a patient is described with goiter,
      recurrent encephalopathy and elevated thyroid peroxidase antibodies who
      apparently responded to steroid therapy; however, magnetic resonance imaging was
      atypical for Hashimoto's encephalopathy, and she was diagnosed with MELAS
      syndrome. This syndrome can present with apparent steroid-responsive
      encephalopathy and elevated thyroid peroxidase antibodies, mimicking Hashimoto's
      encephalopathy, and should be suspected if lactic acidosis is present and typical
      features are detected on magnetic resonance imaging.

PMID- 17560507
TI  - Bilateral perisylvian polymicrogyria and chromosome 1 anomaly.
AB  - Polymalformative syndromes are always a clinical challenge for their complexity
      and sometimes for their rarity. Authors present the case of a girl with peculiar
      facies, macrocephaly, axial hypotonia, and severe development delay. Cerebral
      magnetic resonance showed polymicrogyria. Cytogenetics revealed a
      46,XX,der(1)(qter-->p36.13::q42.3-->qter) karyotype. This is the third case
      described to date. Isolated partial deletions or trisomy, although rare, are more
      frequently reported. None of these genetic findings has ever been related with
      polymicrogyria. Molecular cytogenetic characterization was in this case of great
      value.

PMID- 17560508
TI  - Myotonic dystrophy in a female with myasthenia gravis.
AB  - The likelihood of coexistence in the same patient of myasthenia gravis and
      myotonic dystrophy has been estimated at 1 in 40 million. The case of a patient
      in whom both diagnoses were made is reported here. A 13-year-old girl was
      diagnosed with myasthenia gravis because of weakness, fluctuating fatigability,
      and mild difficulty with chewing and swallowing. She had ptosis, with weakness
      predominantly of her face, arms, and neck. Serum antibodies against acetylcholine
      receptors were 9.9 nmol/L. She was started on pyridostigmine, with significant
      clinical improvement, reassuming normal daily activities. Two years later,
      generalized weakness reappeared and reappraisal of her symptomatology disclosed
      tongue percussion and hand action myotonia. Molecular genetic analysis disclosed
      550 repeats of cytosine-thymidine-guanosine triplets on the DMPK gene.
      Undiagnosed relatives had expansions ranging from 110 to 1000 repeats. Myotonic
      dystrophy is considered the most common muscular dystrophy, with highly variable
      clinical manifestations; mildly affected individuals may escape clinical
      detection. Myasthenia gravis has an estimated prevalence of 15 per 100,000. No
      studies on the epidemiology of these diseases have been done in Chile. Although
      both diseases have specific clinical and laboratory presentations, they share
      some features in the mode of presentation that may generate difficulty in
      diagnosis of both entities in the same patient.

PMID- 17560509
TI  - Home-guided use of the ketogenic diet in a patient for more than 20 years.
AB  - A 26-year-old man with tuberous sclerosis complex and multifocal seizures
      presented to the ketogenic diet clinic for management of his epilepsy. He had
      been started on the ketogenic diet at another institution at age 6 years, and his
      family had managed all nutritional aspects for the previous 10 years. Despite the
      lack of ongoing medical care, excellent seizure control and large urinary ketosis
      had been maintained, and side effects were limited only to poor growth. He
      remains on the diet to date, now for 21 years of continuous duration.

PMID- 17560512
TI  - Advances in metabolic imaging for surgical oncology.
AB  - This review focuses on several aspects of molecular imaging. First, current
      positron emission tomography (PET)/CT scanner technology and several novel
      imaging techniques that are being developed are briefly discussed. Next, current
      clinical indications for (18)F FDG PET and PET/CT that are relevant to the
      surgical oncologist are discussed. Finally, advances in molecular imaging that
      may herald the next generation of PET radiotracers beyond (18)F FDG are reviewed.

PMID- 17560513
TI  - Nanotechnology for sensing, imaging, and treating cancer.
AB  - Nanotechnology encompasses the creation and use of materials, devices, and
      systems at the level of atoms, molecules, and supramolecular structures.
      Nanotechnology for cancer consists of three main areas: (1) nanodetectors for
      sensing proteins and cancer cells, (2) nanoparticle or nanovector formulations
      for high-contrast imaging, and (3) nanotechnology-based drug delivery and
      therapeutic formulations. Although there are tremendous challenges facing
      nanotechnologists, nanotechnology, if properly integrated with established cancer
      research, can make laboratory-to-clinic transfer of technology successful, which
      can result in breakthrough potential for patient care.

PMID- 17560514
TI  - Optical tomography with ultrasound localization for breast cancer diagnosis and
      treatment monitoring.
AB  - Optical tomography with ultrasound (US) localization uses coregistered ultrasound
      images to guide optical imaging reconstruction. To simultaneously acquire US
      images and optical measurements, the authors used a hand-held probe consisting of
      a commercial US transducer and near-infrared optical imaging sensors of multiple
      wavelengths. A novel image scheme was used to map the ultrasound-visible lesions
      for optical imaging reconstruction. As a result, the problem of intense light
      scattering caused by breast tissue was overcome and reliable tumor hemoglobin
      concentration and blood oxygen saturation distributions from a group of patients
      were obtained. These functional parameters are valuable for aiding US diagnosis
      and for assessing chemotherapy response.

PMID- 17560515
TI  - Virtual bronchoscopy: clinical applications and limitations.
AB  - Virtual bronchoscopy (VB) is a term that describes a variety of software-based
      three-dimensional visualizations created from noninvasive medical imaging methods
      such as CT or MRI scans, with the goal of creating results similar to minimally
      invasive bronchoscopy procedures of the trachea and upper airways. This technique
      offers a detailed, noninvasive view of the airways, with reduced risk of
      infection or perforation, and facilitates preoperative planning for airway
      interventions that would otherwise not be possible. It is unlikely that VB will
      replace fiberoptic bronchoscopy; however, as VB techniques become more
      sophisticated and as sufficient computing and imaging power become more readily
      available, noninvasive visualization of the airways will play an important and
      useful role in the evaluation of airway diseases in well defined clinical
      situations.

PMID- 17560516
TI  - Preoperative staging and postoperative surveillance for gastric cancer.
AB  - Physicians must consider multiple factors when determining the most appropriate
      preoperative imaging strategy for gastric cancer. Health care resources are not
      unlimited, and the use of multiple expensive imaging techniques that do not alter
      treatment decisions is not recommended. With this in mind, EGD and CT scan alone
      should form the basis for preoperative evaluation, with further imaging
      considered only in selected cases. Based on the reviewed literature, we do not
      recommend routine surveillance imaging after curative surgery for gastric cancer.
      We agree with current NCCN guidelines that recommend history and physical
      examination every 4 to 6 months for 3 years, followed by yearly examinations.
      Imaging studies and endoscopy should be selectively performed in symptomatic
      patients.

PMID- 17560517
TI  - The use of imaging in the diagnosis and staging of hepatobiliary malignancies.
AB  - This review addresses the optimal use of imaging in the diagnosis, staging, and
      treatment planning of patients with hepatobiliary neoplasms. We focus on primary
      liver cancers, including hepatocellular carcinoma and intrahepatic
      cholangiocarcinoma as well as extrahepatic biliary tract malignancies, including
      hilar cholangiocarcinoma and gallbladder cancer. In each section, we provide an
      overview of the staging requirements for each disease followed by a discussion of
      various imaging modalities that can be used to optimally stage the disease and
      plan therapy.

PMID- 17560518
TI  - Contemporary imaging for colorectal cancer.
AB  - With improvements in therapy for colorectal cancer, accurate imaging has taken on
      an increased significance. Preoperative diagnosis of metastatic disease helps
      identify patients who could undergo combined resection or might benefit from
      systemic therapy before surgery. Accurate imaging of rectal cancer is critical in
      evaluating locally advanced disease treatable by combined modality therapy,
      including chemoradiation and surgery. Postoperative imaging enhances
      identification of recurrent disease that might be amenable to salvage surgery.

PMID- 17560519
TI  - Soft tissue sarcoma: preoperative and postoperative imaging for staging.
AB  - Soft tissue sarcoma (STS) management requires accurate tumor imaging for staging,
      treatment planning, and clinical follow-up. Careful preoperative planning may
      prevent poor primary resections that place the patient at risk for more
      operations, local recurrence, and worse survival. Although MRI may be preferred
      for extremity STS, contrast-enhanced CT is an excellent alternative, with no
      decrease in ability to plan the operative strategy for limb-sparing resection. In
      retroperitoneal and other intra-abdominal STS, double (oral/intravenous) contrast
      enhanced CT evaluates for liver metastases, defines surrounding vital structures
      that might be resected en bloc, identifies margins at risk for local recurrence,
      and shows surrounding organs at risk for toxicity during radiation therapy.
      Postoperative clinical follow-up and imaging must continue even beyond 5 years
      because of the continued risk of long-term relapse.

PMID- 17560520
TI  - Imaging studies in patients with melanoma.
AB  - The incidence of malignant cutaneous melanoma is rising. Imaging studies
      represent a major component of the staging work-up and follow-up of melanoma
      patients and are used to facilitate preoperative planning and intraoperative
      management. Study benefits are not clear, and evidence does not support any
      particular protocol for their use. The National Comprehensive Cancer Network's
      updated guidelines for use of imaging studies in melanoma patients represent a
      consensus based on lower level evidence, including clinical experience. The
      utility of individual imaging studies in melanoma patients depends on disease
      stage. Chest radiography, CT, MRI, lymphoscintigraphy, ultrasonography, PET, and
      PET/CT have specific roles in patient evaluation. Clinicians must use available
      evidence to guide decisions regarding which imaging modalities are appropriate
      for a given indication.

PMID- 17560521
TI  - Contemporary imaging for thyroid cancer.
AB  - Thyroid nodules are extremely common in the adult population of the United
      States, and the incidence of thyroid cancer continues to increase. Preoperative
      ultrasonography is a crucial component of the work up of thyroid nodules. Recent
      studies evaluating (18)F-2-fluoro-2-deoxy-D-glucose-positron-emission-tomography,
      with or without simultaneous computed tomography imaging, are encouraging for its
      potential utility in thyroid cancer in patients who have an elevated serum
      thyroglobulin level and a negative (131)I scan.

PMID- 17560522
TI  - Breast cancer: pre- and postoperative imaging for staging.
AB  - Mammography is considered the "gold standard" in the evaluation of the breast
      from an imaging perspective. Multiple studies have demonstrated the benefit of
      mammography in detecting smaller cancers, leading to identification of early
      stage breast cancers, which largely accounts for decreased mortality from breast
      cancer and the increased rate of breast conservation. Identification of a
      suspicious lesion on a mammogram prompts further evaluation including additional
      mammographic views, ultrasound examination, and biopsy. Recently, MRI and
      positron emission tomography are being offered as adjuncts to the preoperative
      workup to better stage the patient; however, there is still controversy over the
      most appropriate use of these modalities.

PMID- 17560523
TI  - Genetic screening of the lipoprotein lipase gene for mutations in Chinese
      subjects with or without hypertriglyceridemia.
AB  - OBJECTIVE: To investigate the association between the mutations in lipoprotein
      lipase gene and hypertriglyceridemia (HTG). METHODS: The lipoprotein lipase (LPL)
      gene was screened for mutations in 386 Chinese subjects with (108 cases in the
      HTG group) or without HTG (278 cases in the control group), by single-strand
      conformation polymorphism (SSCP) analysis and DNA sequencing. RESULTS: One novel
      silent mutation L103L, one missense mutation P207L, three splicing mutations
      Int3/3'-ass/C(-6) --> T, and the common S447X polymorphism has been identified in
      the whole coding region and exon-intron junctions of the LPL gene were examined.
      Heterozygous P207L found in the HTG group was the first case reported in Asia and
      subsequently another P207L heterozygote was found in the proband's family, all of
      which suggested that P207L was one of the causes of familial combined
      hyperlipidemia, but was not so prevalent as that in French Canadian. Int3/3'
      ass/C(-6) --> T was found in both groups in the present study although it was
      regarded as a pathogenic variant to HTG earlier on. Moreover about the beneficial
      polymorphism S447X, there was also some supportive evidence that the levels of
      triglycerides (TG) in S447X carriers were significantly lower than noncarriers in
      the subjects without HTG. CONCLUSIONS: The association between the LPL variants
      and HTG is quite complicated and versatile, genotyping of LPL in a larger-scale
      screening should be necessary and justifiable.

PMID- 17560524
TI  - Identification of prosaposin as a novel interaction partner for Rhox5.
AB  - Prosaposin (Psap) has multiple cellular functions. It is involved in the
      development of the reproductive system, nervous system, and prostate cancer as
      well as in the regulation of sphingolipid catabolism by activating several
      lysosomal hydrolases involved in the metabolism of various sphingolipids. In this
      research, it was found to be a novel interaction partner for Rhox5 using yeast
      two-hybrid screening. The interaction between Rhox5 and the full-length
      prosapsoin (the transcript without exon 8) as well as the C-terminal domain of
      prosaposin, was further confirmed in both yeast two hybrid analysis and in vitro
      assay. It suggested that the C-terminal domain of prosaposin may be critical for
      the Rhox5-prosaposin interaction. Given the important roles played by both Rhox5
      and prosaposin in maintaining the differentiation of male reproductive organs,
      spermatogenesis, and fertilization, the interaction between Rhox5 and prosaposin
      might regulate the development of male reproductive organs dynamically.

PMID- 17560525
TI  - Association of polymorphisms of leptin gene with body weight and body sizes
      indexes in Chinese indigenous cattle.
AB  - PCR-SSCP was used to analyze the polymorphism of leptin gene in 539 samples of
      six cattle breeds, namely Nanyang (NY), Qinchuan (QC), Jiaxianred (JXR), Xizhen
      (XZ), Luxi (LX), and Holstein cow (HOL) breeds. PCR products with a 330 bp were
      amplified and sequenced. The results showed that the frequencies of alleles A/B
      of NY, QC, JXR, XZ, LX, and HOL breeds were 0.558/0.442, 0.492/0.508,
      0.571/0.429, 0.658/0.342, 0.591/0.409, and 0.615/0.385, respectively. The
      association of variations of leptin gene with growth traits in NY, QC, JXR breeds
      was analyzed. Some indexes of the individuals with genotype BB were higher than
      that with genotype AA and AB in NY breed, such as the indexes of body length,
      heart length, body weight, hucklebone width, body height, and average day gain.
      The height at hip cross of the individuals with genotype BB was higher than that
      of those with genotype AA and AB in QC breed (P < 0.05). So leptin gene may be
      one of the candidate genes for growth traits with height at hip cross, but not
      for body weight, heart length, and body length trait. However, the height at hip
      cross and hucklebone width of the individuals with genotype AB and BB were higher
      than that of those with genotype AA in JXR breed (P < 0.05), but the difference
      was not statistically significant in body weight and body sizes (body height,
      body length, and heart length). And the polymorphisms in leptin gene were caused
      by G --> T transversion at the 66th bp position, A --> C transversion at the 67th
      bp position and G --> T transversion at the 299th bp position. These results may
      be applied to marker-assisted selection of Chinese cattle breeds.

PMID- 17560526
TI  - Genetic polymorphism of TLR4 gene and correlation with mastitis in cattle.
AB  - Toll-like receptor 4 (TLR4) recognizes pathogen ligands and mediates signaling to
      initiate innate and adaptive immune responses. In this experiment, a 316 bp and
      382 bp fragments of TLR4 gene named T4CRBR1 and T4CRBR2, of Chinese Holstein,
      Sanhe cattle, and Chinese Simmental was amplified by polymerase chain reaction
      (PCR), respectively. The genetic polymorphisms in the three populations were
      detected by Single-Strand Conformational Polymorphism (SSCP) in the first locus
      and by digesting the fragments with restriction endonuclease Alu? in the second
      one. Results showed that both alleles (A and B) of two loci were found in all the
      three populations and the value of polymorphism information content (PIC)
      indicated that these were a moderate polymorphism. Statistical results of chi(2)
      test indicated that two polymorphism sites in the three populations fitted with
      Hardy-Weinberg equilibrium (P > 0.05). After sequencing, A-G single nucleotide
      polymorphism (SNP) was identified at nucleotide 4,525 in intron 1 of TLR4 gene
      and C-T SNP was identified at nucleotide 1,397 in exon 3 of TLR4 gene. Meanwhile,
      the effect of polymorphism of TLR4 gene on somatic cell score (SCS) was analyzed,
      the results indicated that the cattle with allele A in T4CRBR1 showed lower
      somatic cell score than that of allele B (P < 0.05). In short, the allele A might
      play an important role in mastitis resistance in bovine.

PMID- 17560527
TI  - Phylogenetic relationships and status quo of colonies for gayal based on analysis
      of cytochrome B gene partial sequences.
AB  - Thirty-three mutations and four different haplotypes were found when cytochrome
      b(Cytb) gene partial sequences of 12 gayals were analyzed. Together with
      sequences of Bos indicus, Bos taurus, Bos grunniens and Bos gaurus with Bubalus
      bubalis as the out group, the partial sequences of Cytb gene of gayals were
      aligned and base composition and nucleotide variation of Cytb gene were analyzed.
      The phylogenetic trees were constructed by the NJ method and the MP method
      respectively, both supporting almost the same topology. Gayal is an independent
      species of Bos from Bos indicus, Bos taurus and Bos gaurus. The results also
      indicate that a great proportion of gayal bloodline was invaded by other species,
      and the protection of gayal is facing a formidable situation.

PMID- 17560528
TI  - QTL mapping and QxE interactions of grain cooking and nutrient qualities in rice
      under upland and lowland environments.
AB  - Grain cooking and nutrient qualities are the most important components of rice
      (Oryza sativa L.) quality. A doubled haploid (DH) population from a cross between
      two japonica cultivars was used to examine the phenotypic values and potential
      QTLs for the quality traits. The cooking and nutrient quality traits, including
      the amylose content (AC), the gel consistency (GC), the gelatinization
      temperature (GT), and the protein content (PC), in rice grown under upland and
      lowland environments were evaluated. Significant differences for AC, GC, GT, and
      PC between upland and lowland environments were detected. The phenotypic values
      of all four traits were higher under upland environment than lowland environment.
      The value of PC under upland environment was significantly higher (by 37.9%) than
      that under lowland environment. This suggests that upland cultivation had large
      effect on both cooking and nutrient qualities. A total of seven QTLs and twelve
      pairs of QTLs were detected to have significant additive and epistatic effects
      for the four traits. Significant Q x E interaction effects of two QTLs and two
      pairs of QTLs were also discovered. The general contribution of additive QTLs
      ranged from 1.91% to 19.77%. The Q x E interactions of QTLs QGt3 and QAc6
      accounted for 8.99% and 47.86% of the phenotypic variation, respectively, whereas
      those of the 2 pairs of epistatic QTLs, QAc6-QAc11b and QAc8-QAc9, accounted for
      32.54% and 11.82%, respectively. Five QTLs QGt6b, QGt8, QGt11, QGc1, and QPc2,
      which had relatively high general contribution and no Q x E interactions, were
      selected to facilitate the upland rice grain quality breeding.

PMID- 17560529
TI  - Interval mapping of quantitative trait loci underlying triploid endosperm traits
      using F3 seeds.
AB  - A statistical method for mapping quantitative trait loci (QTLs) underlying
      endosperm traits is proposed. The method is based on a genetic model containing
      both the direct effects and maternal effects of an endosperm QTL and on an
      experimental design termed two-stage hierarchical design, in which the trait
      information is obtained from F(3) endosperms and molecular marker information is
      obtained from F(2) plants and F(3) embryos (plants). Results of computer
      simulations indicate that the method can efficiently map endosperm QTLs and
      precisely estimate both the direct and maternal effects of endosperm QTLs when
      the sample size is sufficiently large.

PMID- 17560530
TI  - The distribution of repetitive DNAs along chromosomes in plants revealed by self
      genomic in situ hybridization.
AB  - The distribution of repetitive DNAs along chromosomes is one of the crucial
      elements for understanding the organization and the evolution of plant genomes.
      Using a modified genomic in situ hybridization (GISH) procedure, fluorescence in
      situ hybridization (FISH) with genomic DNA to their own chromosomes (called self
      genomic in situ hybridization, self-GISH) was carried out in six selected plant
      species with different genome size and amount of repetitive DNA. Nonuniform
      distribution of the fluorescent labeled probe DNA was observed on the chromosomes
      of all the species that were tested. The signal patterns varied among species and
      were related to the genome size. The chromosomes of the small Arabidopsis genome
      were labeled almost only in the pericentromeric regions and the nucleolus
      organizer regions (NORs). The signals in the relatively small genomes, rice,
      sorghum, and Brassica oleracea var. capitata L., were dispersed along the
      chromosome lengths, with a predominant distribution in the pericentromeric or
      proximal regions and some heterochromatic arms. All chromosomes of the large
      genomes, maize and barley, were densely labeled with strongly labeled regions and
      weakly labeled or unlabeled regions being arranged alternatively throughout the
      lengths. In addition, enhanced signal bands were shown in all pericentromeres and
      the NORs in B. oleracea var. capitata and in all pericentromeric regions and
      certain intercalary sites in barley. The enhanced signal band pattern in barley
      was found consistent with the N-banding pattern of this species. The GISH with
      self-genomic DNA was compared with FISH with C(o)t-1 DNA in rice, and their
      signal patterns are found to be basically consistent. Our results showed that the
      self-GISH signals actually reflected the hybridization of genomic repetitive DNAs
      to the chromosomes, thus the self-GISH technique would be useful for revealing
      the distribution of the regions where repetitive DNAs concentrate along
      chromosomes and some chromatin differentiation associated with repetitive DNAs in
      plants.

PMID- 17560531
TI  - Genetic diversity in cultivated groundnut based on SSR markers.
AB  - Peanut (Arachis hypogaea L.) is an important source crop for edible oil and
      protein. It is important to identify the genetic diversity of peanut genetic
      resources for cultivar development and evaluation of peanut accessions. Thirty
      four SSR markers were used to assess the genetic variation of four sets of twenty
      four accessions each from the four botanical varieties of the cultivated peanut.
      Among the tested accessions, ten to sixteen pairs of SSR primers showed
      polymorphisms. The maximum differentiation index, which was defined as the degree
      of genetic differentiation, was as high as 0.992 in the tested accessions. Each
      accession could be discriminated by a specific set of polymorphic SSR primers,
      and the intra-variety genetic distance was determined among accessions, with an
      average of 0.59 in var. fastigiata 0.46 in var. hypogaea 0.38 in var. vulgaris
      and 0.17 in var. hirsuta. Dendrogrames based on genetic distances were
      constructed for the four botanical varieties, which revealed the existence of
      different clusters. It was concluded that there was abundant intra-variety SSR
      polymorphism, and with more and more SSR markers being developed, the intrinsic
      genetic diversity would be detected and the development of genetic map and marker
      assisted selection for cultivated peanut would be feasible.

PMID- 17560532
TI  - Production of partial new-typed Brassica napus by introgression of genomic
      components from B. rapa and B. carinata.
AB  - A breeding strategy for widening the germplasm of Brassica napus was proposed by
      introgression of the A(r) subgenome of B. rapa (A(r)A(r)) and C(c) of B. carinata
      (B(c)B(c)C(c)C(c)) into natural B. napus (A(n)A(n)C(n)C(n)). The progenies with
      38 chromosomes that were derived from the self-pollinated seeds of pentaploid
      hybrids (A(r)A(n)B(c)C(c)C(n)) were used for further research. Some of the
      partial new-typed B. napus showed normal meiotic behavior, high portion of
      germinated pollen and normal embryological development. This indicates that the
      selected new-typed B. napus had a balanced genetic base. Molecular analysis
      showed that about 50% of the genome in the new-typed B. napus was replaced by
      A(r) and C(c) subgenome from B. rapa and B. carinata. Considering the genetic
      diversity among different lines of new-typed B. napus it was deduced that the
      introgression of the genomic components from B. rapa and B. carinata could widen
      the genetic diversity of rapeseed.

PMID- 17560533
TI  - Genetic study on JS399-19 resistance in hyphal fusion of Fusarium graminearum by
      using nitrate nonutilizing mutants as genetic markers.
AB  - Twenty-two nitrate nonutilizing (nit) mutants were recovered from five wild-type
      isolates of Fusarium graminearum and fifty nit mutants were recovered from three
      JS399-19-resistant mutants of F. graminearum cultured on MMC medium. Some
      biological properties were compared between nit mutants and their parental
      isolates. The results showed that there were no significant differences in growth
      rate, cultural characters or pathogenicity between JS399-19-resistant nit mutants
      and their parental isolates. But the conidial production and the sexual
      reproduction ability changed to some extent. There was no cross resistance toward
      chlorate and JS399-19 in F. graminearum and the resistance could be stable
      through 20-time subcultures. Therefore, the nit could be used as a genetic marker
      for studying the genetics of JS399-19 resistance in F. graminearum which was used
      to study JS399-19 resistance transferability in hyphal fusion. Resistance in
      JS399-19 could not be transferred by hyphal fusion or could be transferred with
      low chance between two compatible isolates, which would delay the development of
      JS399-19 resistance in the field.

PMID- 17560534
TI  - Sedimentation in nano-colloidal dispersions: effects of collective interactions
      and particle charge.
AB  - This is a review paper summarizing the progress of the development of colloidal
      sedimentation models for monodisperse, bidisperse, and polydisperse nanoparticle
      dispersions. This topic is of considerable interest because the sedimentation
      behavior of nanoparticles plays an important role in many practical systems, such
      as industrial coatings, optical products, ceramics, paints, dyes, and cosmetics.
      The limitations of various models are discussed. Multi-particle systems are
      highlighted, with a focus on the collective thermodynamic interactions resulting
      in the attractive depletion and repulsive structural forces. The effects of the
      particle concentration, particle charge, polydispersity in size, and electrolyte
      concentration on the sedimentation process are briefly summarized. Our
      contributions to this subject are reviewed.

PMID- 17560535
TI  - Probing the structure and activity of trypsin with amidination.
AB  - Trypsin reacts with S-methylisothiourea for 1 to 2 h and the number of primary
      amine sites at which covalent labeling occurs is determined by mass spectrometry.
      By digesting the amidinated trypsin and mass analyzing the proteolytic peptides
      the sites of reaction are determined. The addition of cytochrome c to a solution
      of amidinated trypsin enables the proteolytic activity and autolytic properties
      of the enzyme to be studied.

PMID- 17560536
TI  - Respiratory chain components involved in the glycerophosphate dehydrogenase
      dependent ROS production by brown adipose tissue mitochondria.
AB  - Involvement of mammalian mitochondrial glycerophosphate dehydrogenase (mGPDH, EC
      1.1.99.5) in reactive oxygen species (ROS) generation was studied in brown
      adipose tissue mitochondria by different spectroscopic techniques.
      Spectrofluorometry using ROS-sensitive probes CM-H2DCFDA and Amplex Red was used
      to determine the glycerophosphate- or succinate-dependent ROS production in
      mitochondria supplemented with respiratory chain inhibitors antimycin A and
      myxothiazol. In case of glycerophosphate oxidation, most of the ROS originated
      directly from mGPDH and coenzyme Q while complex III was a typical site of ROS
      production in succinate oxidation. Glycerophosphate-dependent ROS production
      monitored by KCN-insensitive oxygen consumption was highly activated by one
      electron acceptor ferricyanide, whereas succinate-dependent ROS production was
      unaffected. In addition, superoxide anion radical was detected as a mGPDH-related
      primary ROS species by fluorescent probe dihydroethidium, as well as by electron
      paramagnetic resonance (EPR) spectroscopy with DMPO spin trap. Altogether, the
      data obtained demonstrate pronounced differences in the mechanism of ROS
      production originating from oxidation of glycerophosphate and succinate
      indicating that electron transfer from mGPDH to coenzyme Q is highly prone to
      electron leak and superoxide generation.

PMID- 17560537
TI  - Exposing the complex III Qo semiquinone radical.
AB  - Complex III Qo site semiquinone has been assigned pivotal roles in productive
      energy-conversion and destructive superoxide generation. After a 30-year search,
      a genetic heme bH knockout arrests this transient semiquinone EPR radical,
      revealing the natural engineering balance pitting energy-conserving, short
      circuit minimizing, split electron transfer and catalytic speed against damaging
      oxygen reduction.

PMID- 17560538
TI  - Changes in the LHCII-mediated energy utilization and dissipation adjust the
      methanol-induced biomass increase.
AB  - Considerably low methanol concentrations of 0.5% (v/v), induce an immense
      increase in biomass production in cultures of the unicellular green alga
      Scenedesmus obliquus compared to controls without additional methanol. The effect
      is light-regulated and it mimics high-CO2 induced changes of the molecular
      structure and function of the photosynthetic apparatus. There is evidence that
      methanol enhances under high light conditions by molecular changes in the LHCII-
      a decrease of the functional antenna-size per active reaction center--the
      photochemical effectiveness of the absorbed energy. This means that the non
      photochemical quenching (NPQ) is minimized and thereby the overall dissipation
      energy. Experiments with mutants of Scenedesmus Wt produced evidence that the
      LHCII is the locus of the mechanism which regulates the methanol effect. The
      employed mutants were Wt-LHC, lacking a functioning LHCII, the light-dependent
      greening mutant C-2A', and the double mutant C-2A'-LHC, combining both mutations.

PMID- 17560539
TI  - Solution structures and model membrane interactions of lactoferrampin, an
      antimicrobial peptide derived from bovine lactoferrin.
AB  - Bovine lactoferrampin (LFampinB) has been identified as a novel antimicrobial
      peptide, which is derived from the N-terminal lobe of bovine lactoferrin. In this
      study, the solution structure of LFampinB bound to negatively charged sodium
      dodecyl sulphate micelles and zwitterionic dodecyl phosphocholine micelles was
      determined using 2-dimensional nuclear magnetic resonance (NMR) spectroscopy. The
      interaction between LFampinB and multilamellar phospholipid vesicles, containing
      choline and glycerol head groups, was examined using differential scanning
      calorimetry (DSC). In addition, the interaction between the N-terminal tryptophan
      residue and model membranes of varying composition was analyzed by fluorescence
      spectroscopy. LFampinB adopts an amphipathic alpha-helical conformation across
      the first 11 residues of the peptide but remains relatively unstructured at the C
      terminus. The hydrophobic surface of the amphipathic helix is bordered by the
      side chains of Trp1 and Phe11, and is seen in both micelle-bound structures. The
      fluorescence results suggest that Trp1 inserts into the membrane at the
      lipid/water interface. The phenyl side chain of Phe11 is oriented in the same
      direction as the indole ring of Trp1, allowing these two residues to serve as
      anchors for the lipid bilayer. The DSC results also indicate that LFampinB
      interacts with glycerol head groups in multilamellar vesicles but has little
      effect on acyl chain packing. Our results support a two step model of
      antimicrobial activity where the initial attraction of LFampinB is mediated by
      the cluster of positive charges on the C-terminus followed by the formation of
      the N-terminal helix which binds to the surface of the bacterial lipid bilayer.

PMID- 17560540
TI  - Prediction of HIV-1 entry inhibitors neomycin-arginine conjugates interaction
      with the CD4-gp120 binding site by molecular modeling and multistep docking
      procedure.
AB  - Developing of multi-target HIV-1 entry inhibitors represents an important avenue
      of drug therapy. Two such inhibitors are hexa-arginine-neomycin-conjugate (NeoR6)
      and nona-d-arginine-neomycin-conjugate (Neo-r9). Our findings that NeoR6
      resistant mutations appear in the gp120 constant regions; and NeoR6 is not CCR5
      antagonist, but inhibits CXCR4 and CCR5 HIV-1 using isolates, led us to suggest
      that NeoR6 may inhibit HIV-1 entry by interfering with the CD4-gp120 binding. To
      support this notion, we constructed a homology model of unliganded HIV-1(IIIB)
      gp120 and docked NeoR6 and Neo-r9 to it, using a multistep docking procedure:
      geometric-electrostatic docking by MolFit; flexible ligand docking by Autodock3
      and final refinement of the obtained complexes by Discover3. Binding free
      energies were calculated by MM-PBSA methodology. The model predicts competitive
      inhibition of CD4-gp120 binding by NeoR6 and Neo-r9. We determined plausible
      binding sites between constructed CD4-bound gp120 trimer and homology modeled
      membranal CXCR4, and tested NeoR6 and Neo-r9 interfering with this interaction.
      These models support our notion that another mechanism of anti-HIV-1 activity of
      NeoR6 is inhibition of gp120-CXCR4 binding. These structural models and
      interaction of NeoR6 and Neo-r9 with gp120 and CXCR4 provide a powerful approach
      for structural based drug design for selective targeting of HIV-1 entry and/or
      for inhibition of other retroviruses with similar mechanism of entry.

PMID- 17560541
TI  - A prospective study of appraisals in childhood posttraumatic stress disorder.
AB  - This study investigated the predictors of posttraumatic stress disorder (PTSD) in
      children following a diagnosis of traumatic injury. Children (N=76) aged between
      7 and 13 who were admitted to hospital following injury were assessed within a
      month of trauma for acute stress disorder (ASD), negative appraisals, as well as
      parental stress reactions. Children (N=62) were re-assessed 6-months later for
      PTSD and negative appraisals. The majority of the variance of chronic
      posttraumatic stress was accounted for by negative appraisals about future harm.
      This study supports cognitive models of PTSD, and suggests that younger children
      who exaggerate their vulnerability after trauma exposure are high risk for PTSD
      after trauma.

PMID- 17560542
TI  - Interaction between the aryl hydrocarbon receptor and its antagonists,
      flavonoids.
AB  - Flavonoids have been reported to be dietary antagonists of an aryl hydrocarbon
      receptor (AhR). However, little is known about the molecular mechanism on their
      antagonistic effects. In this study, the inhibitory effect of flavonoids on
      ligand binding to the AhR and interaction between flavonoids and the AhR complex
      (AhRc) were investigated in each flavonoid subclass. Flavone, flavonol, and
      flavanone but not catechin inhibited the specific binding between the AhR and 3
      methylcholanthrene dose-dependently, indicating that the former three subclasses
      possibly act as competitive antagonists of the AhR. However, catechin in addition
      to the former three subclasses directly interacted with the AhRc by surface
      plasmon resonance analysis. The dissociation constant values showed an inverse
      correlation with the suppressive effect on the DNA binding activity. These
      results suggest that flavone, flavonol, and flavanone act as competitive
      antagonists of the AhR, while catechin associates with the AhRc and indirectly
      exhibits its antagonistic effects.

PMID- 17560543
TI  - ATM phosphorylates ZBP-89 at Ser202 to potentiate p21waf1 induction by butyrate.
AB  - Histone deacetylase inhibitors (HDACi) induce growth arrest and differentiation,
      particularly in the colon where they are potential chemotherapeutic agents. A key
      mediator of HDACi action is the cyclin dependent kinase (CDK) inhibitor
      p21(waf1). HDACi treatment of colonic cells promotes the formation of an ATM/ZBP
      89/p300 complex on p21(waf1) proximal promoter, and this multi-molecular complex
      plays an important role in HDACi induction of p21(waf1) expression in vitro and
      mucosal protection in vivo. Here we found that ZBP-89 is phosphorylated by ATM
      kinase in vitro and in vivo. Disruption of the ATM phosphorylation motif (202)SQ
      within the zinc finger domain of ZBP-89 attenuated its ability to enhance
      p21(waf1) activation by butyrate. Moreover, disruption of the ATM phosphorylation
      site abrogated the ability of ZBP-89 to potentiate butyrate induction of
      endogenous p21(waf1) expression. These results demonstrate that ATM
      phosphorylation of ZBP-89 contributes to HDACi induction of p21(waf1) gene
      expression.

PMID- 17560544
TI  - Ghrelin protects cortical neuron against focal ischemia/reperfusion in rats.
AB  - Ghrelin is a novel brain-gut peptide and the endogenous ligand of growth hormone
      secretagogue receptor 1a (GHSR-1a). Evidences have been shown that ghrelin
      inhibited cell apoptosis in cardiocytes, endotheliocytes, osteoblasts, and so on.
      Recently, it was reported that ghrelin inhibited neuronal apoptosis of
      hypothalamus and hippocampus. However, little is known about the effects of
      ghrelin on cortical neurons during focal ischemia/reperfusion injury. In the
      present study, we showed that ghrelin (i.v.) prevented cortical neurons from
      injury induced by ischemia/reperfusion in vivo and by LPS, glutamate, NMDA and
      H(2)O(2) in vitro. We found that the expression of ghrelin's receptor (GHSR-1a)
      in rat cerebral cortex were obviously decreased by ischemia/reperfusion injury
      and increased by ghrelin (i.v.). Ghrelin up-regulated the expression of Bcl-2/Bax
      and HSP70, and inhibited caspase8, 9, 3 through GHSR-1a, which was contributed to
      the neuroprotective mechanism of ghrelin. Ghrelin might be an important regulator
      in therapeutic strategy of cortex injury.

PMID- 17560545
TI  - A comparative molecular dynamics study on thermostability of human and chicken
      prion proteins.
AB  - To compare the thermostabilities of human and chicken normal cellular prion
      proteins (HuPrP(C) and CkPrP(C)), molecular dynamics (MD) simulations were
      performed for both proteins at an ensemble level (10 parallel simulations at 400
      K and 5 parallel simulations at 300 K as a control). It is found that the
      thermostability of HuPrP(C) is comparable with that of CkPrP(C), which implicates
      that the non-occurrence of prion diseases in non-mammals cannot be completely
      attributed to the thermodynamic properties of non-mammalian PrP(C).

PMID- 17560546
TI  - Drosophila dSet2 functions in H3-K36 methylation and is required for development.
AB  - Lysine methylation has important functions in biological processes that range
      from heterochromatin formation to transcription regulation. Here, we demonstrate
      that Drosophila dSet2 encodes a developmentally essential histone H3 lysine 36
      (K36) methyltransferase. Larvae subjected to RNA interference-mediated (RNAi)
      suppression of dSet2 lack dSet2 expression and H3-K36 methylation, indicating
      that dSet2 is the sole enzyme responsible for this modification in Drosophila
      melanogaster. dSet2 RNAi blocks puparium formation and adult development, and
      causes partial (blister) separation of the dorsal and ventral wing epithelia,
      defects suggesting a failure of the ecdysone-controlled genetic program. A
      transheterozygous EcR null mutation/dSet2 RNAi combination produces a complete
      (balloon) separation of the wing surfaces, revealing a genetic interaction
      between EcR and dSet2. Using immunoprecipitation, we demonstrate that dSet2
      associates with the hyperphosphorylated form of RNA polymerase II (RNAPII).

PMID- 17560547
TI  - The role of nitric oxide in muscle fibers with oxidative phosphorylation defects.
AB  - NO has been pointed as an important player in the control of mitochondrial
      respiration, especially because of its inhibitory effect on cytochrome c oxidase
      (COX). However, all the events involved in this control are still not completely
      elucidated. We demonstrate compartmentalized abnormalities on nitric oxide
      synthase (NOS) activity on muscle biopsies of patients with mitochondrial
      diseases. NOS activity was reduced in the sarcoplasmic compartment in COX
      deficient fibers, whereas increased activity was found in the sarcolemma of
      fibers with mitochondrial proliferation. We observed increased expression of
      neuronal NOS (nNOS) in patients and a correlation between nNOS expression and
      mitochondrial content. Treatment of skeletal muscle culture with an NO donor
      induced an increase in mitochondrial content. Our results indicate specific roles
      of NO in compensatory mechanisms of muscle fibers with mitochondrial deficiency
      and suggest the participation of nNOS in the signaling process of mitochondrial
      proliferation in human skeletal muscle.

PMID- 17560548
TI  - Effect of KAI1/CD82 on the beta1 integrin maturation in highly migratory
      carcinoma cells.
AB  - The KAI1/CD82 protein has been documented as the tumor metastasis suppressor in
      many types of human cancers. KAI1/CD82 regulates cell motility and invasiveness;
      however, the mechanism by which this occurs remains to be fully established.
      Several studies have shown that KAI1/CD82 modulates integrin-dependent signaling.
      It was suggested that KAI1/CD82 might function to attenuate the beta1 integrin
      function of inducing cellular migration. A wound-healing and modified Boyden
      chamber assays were performed to investigate the mechanism of the KAI1/CD82
      mediated inhibition of cell migration. It was found that the migratory ability of
      H1299/CD82 was inhibited. The immunoblotting and biotinylation assays revealed
      that H1299/CD82 showed significantly decreased expression of the mature form of
      beta1, which was functional at the cell surface. It was confirmed that KAI1/CD82
      regulates the maturation of the beta1 integrin using CD82-specific si-RNA. These
      results support a model in which KAI1/CD82 attenuates the maturation of the beta1
      integrin precursor and thereby suppresses cell migration.

PMID- 17560549
TI  - Resveratrol abolishes resistance to axonal degeneration in slow Wallerian
      degeneration (WldS) mice: activation of SIRT2, an NAD-dependent tubulin
      deacetylase.
AB  - Resveratrol is a natural polyphenol having a wide range of biological and
      pharmacological activities. Here we have investigated the effect of resveratrol
      on neurodegeneration in cultured cerebellar granule cells from slow Wallerian
      degeneration (Wld(S)) mice, characteristic of substantial delay of degeneration
      in the distal stump of transected axons. Resveratrol diminished resistance of
      Wld(S) neurons to axonal degeneration induced by colchicine, a microtubule
      depolymerizing drug. Resveratrol also decreased the level of tubulin acetylation
      in Wld(S) neurons and their homogenates. This promoting effect on tubulin
      deacetylation was mimicked by NAD, suggesting the involvement of SIRT2, an NAD
      dependent tubulin deacetylase. Indeed, resveratrol promoted tubulin deacetylation
      in the presence of GFP-SIRT2 but not GFP-SIRT2 N168A, a catalytically inactive
      mutant. Moreover, SIRT2 silencing restored the resistance to axonal degeneration
      in resveratrol-treated Wld(S) neurons. These results suggest that resveratrol
      abolishes the resistance of Wld(S) mice to axonal degeneration by enhancing SIRT2
      mediated tubulin deacetylation.

PMID- 17560550
TI  - The real factor for polypeptide elongation in Dictyostelium cells is EF-2B, not
      EF-2A.
AB  - Polypeptide elongation factor 2 (EF-2) plays an essential role in protein
      synthesis and is believed to be indispensable for cell proliferation. Recently,
      it has been demonstrated that there are two kinds of EF-2 (EF-2A and EF-2B with
      76.6% of sequence identity at the amino acid level) in Dictyostelium discoideum.
      Although the knockout of EF-2A slightly impaired cytokinesis, EF-2A null cells
      exhibited almost normal protein synthesis and cell growth, suggesting that there
      is another molecule capable of compensating for EF-2 function. Since EF-2B is the
      most likely candidate, we examined its function using ef-2b knockdown cells
      prepared by the RNAi method. Our results strongly suggest that EF-2B is required
      for protein synthesis and cell proliferation, functioning as the real EF-2.
      Interestingly, the expressions of ef-2a and ef-2b mRNAs during development are
      reversely regulated, and the ef-2b expression is greatly augmented in ef-2a null
      cells.

PMID- 17560551
TI  - Stable transcriptional status in the apoptotic erythroid genome.
AB  - When a cell is destined for apoptosis, will its genome reprogram its
      transcriptional machinery to overcome the life-threatening challenge? To address
      this issue, we performed a genome-wide transcriptome analysis in EPO
      (erythropoietin) deprivation-induced apoptotic erythroid cells using the SAGE
      method. The results show that the transcript contents for the majority of the
      genes remain unchanged in the apoptotic cells, including the apoptotic genes and
      the heat shock genes. Of the small number of genes with an altered expression,
      they are mainly associated with cellular structure. Our study reveals that there
      is no genetic reprogramming for the transcriptional machinery in the apoptotic
      genome. Apoptosis, as defined by programmed cell death, is not a crisis but a
      peaceful physiological process.

PMID- 17560552
TI  - NF-kappaB inhibition by an adenovirus expressed aptamer sensitizes TNFalpha
      induced apoptosis.
AB  - Prolonged activation of NF-kappaB is involved in the pathogenesis of chronic
      inflammatory diseases and associated cancers. NF-kappaB activation is considered
      to be a main mechanism opposing TNFalpha-induced apoptosis. We investigated
      whether inhibition of NF-kappaB could sensitize tumor and endothelial cells to
      TNFalpha-induced apoptosis. As such, we developed a novel H1 RNA polymerase III
      promoter driven adenoviral vector to express an RNA aptamer, Ad-A-p50, which
      selectively inhibits NF-kappaB activation in the nucleus. This event sensitizes
      human lung adenocarcinoma cells (A549) and human endothelial cells (HUVEC) to
      TNFalpha-induced apoptosis through the multiple pathways regulated by NF-kappaB,
      including Bcl-XL, HIF-1alpha, and VEGF. Our findings also suggest a new mechanism
      of HIF-1alpha regulation by NF-kappaB in the normoxic environment. RNA aptamer
      inhibition of NF-kappaB offers exciting opportunities for sensitizing
      inflammatory and tumor cells to TNFalpha-induced apoptosis.

PMID- 17560553
TI  - Blockade of TGF-beta accelerates mucosal destruction through epithelial cell
      apoptosis.
AB  - To clarify the protective role of transforming growth factor (TGF)-beta for the
      intestinal epithelial injury in vivo, the effect of antibodies against TGF-beta
      on epithelial destruction and apoptosis was assessed in dextran sulfate sodium
      (DSS)-induced colitis by histological analysis of colonic sections, account of
      apoptotic epithelial cells. To evaluate the pathways of epithelial apoptosis, we
      analyzed the activities of caspases, the level of Fas and cellular FLICE
      inhibitory protein (cFLIP) expression in epithelial cells. Apoptotic epithelial
      cells were increased prior to the onset of ulceration in DSS-induced colitis, and
      the neutralization of TGF-beta exacerbated epithelial apoptosis and histological
      damage score. The up-regulation of caspase-8 activity and Fas expression and
      reduced cFLIP expression were observed in intestinal epithelial cells from anti
      TGF-beta antibody-treated mice. The present study revealed that suppression of
      TGF-beta deteriorated epithelial apoptosis, and the increase of apoptotic
      epithelial cells may amplify the inflammation in gut mucosa.

PMID- 17560554
TI  - Inhibition of the HERG potassium channel by the tricyclic antidepressant doxepin.
AB  - HERG (human ether-a-go-go-related gene) encodes channels responsible for the
      cardiac rapid delayed rectifier potassium current, I(Kr). This study investigated
      the effects on HERG channels of doxepin, a tricyclic antidepressant linked to QT
      interval prolongation and cardiac arrhythmia. Whole-cell patch-clamp recordings
      were made at 37 degrees C of recombinant HERG channel current (I(HERG)), and of
      native I(Kr) 'tails' from rabbit ventricular myocytes. Doxepin inhibited I(HERG)
      with an IC(50) value of 6.5+/-1.4 microM and native I(Kr) with an IC(50) of 4.4+/
      0.6 microM. The inhibitory effect on I(HERG) developed rapidly upon membrane
      depolarization, but with no significant dependence on voltage and with little
      alteration to the voltage-dependent kinetics of I(HERG). Neither the S631A nor
      N588K inactivation-attenuating mutations (of residues located in the channel pore
      and external S5-Pore linker, respectively) significantly reduced the potency of
      inhibition. The S6 point mutation Y652A increased the IC(50) for I(HERG) blockade
      by approximately 4.2-fold; the F656A mutant also attenuated doxepin's action at
      some concentrations. HERG channel blockade is likely to underpin reported cases
      of QT interval prolongation with doxepin. Notably, this study also establishes
      doxepin as an effective inhibitor of mutant (N588K) HERG channels responsible for
      variant 1 of the short QT syndrome.

PMID- 17560555
TI  - Partial replication of a DRD4 association in ADHD individuals using a
      statistically derived quantitative trait for ADHD in a family-based association
      test.
AB  - BACKGROUND: Previous research found an association between single nucleotide
      polymorphisms (SNPs) in the promoter region of DRD4 and statistically derived
      phenotypes generated from attention-deficit/hyperactivity disorder (ADHD)
      symptoms. We sought to replicate this finding by using the same methodology in an
      independent sample of ADHD individuals. METHODS: Four SNPs were genotyped in and
      around DRD4 in 2631 individuals in 642 families. We developed a quantitative
      phenotype at each SNP by weighting nine inattentive and nine hyperactive
      impulsive symptoms. The weights were selected to maximize the heritability at
      each SNP. Once a quantitative phenotype was generated at each SNP, the screening
      procedure implemented in PBAT was used to select and test the five SNPs/genetic
      model combinations with the greatest power to detect an association for DRD4.
      RESULTS: One of the four SNPs was associated with the quantitative phenotypes
      generated from the ADHD symptoms (corrected p-values = .02). A rank ordering of
      the correlation between each of the ADHD symptoms and the quantitative phenotype
      suggested that hyperactive-impulsive symptoms were more strongly correlated with
      the phenotype; however, including inattentive symptoms was necessary to achieve a
      significant result. CONCLUSIONS: This study partially replicated a previous
      finding by identifying an association between rs7124601 and a quantitative trait
      generated from ADHD symptoms. The rs7124601 is in linkage disequilibrium (LD)
      with the SNPs identified previously. In contrast to the previous study, this
      finding suggests that both hyperactive-impulsive and inattentive symptoms are
      important in the association.

PMID- 17560556
TI  - Correlation between serum brain-derived neurotrophic factor level and an in vivo
      marker of cortical integrity.
AB  - BACKGROUND: Brain-derived neurotrophic factor (BDNF) signaling at synapses
      improves synaptic strengthening associated with learning and memory. In the
      present study we hypothesized that serum BDNF concentration is associated with in
      vivo level of cerebral N-acetylaspartate (NAA), a well established marker of
      neuronal integrity. METHODS: In 36 healthy subjects BDNF serum concentration and
      absolute concentration of NAA together with other metabolites were measured by
      proton magnetic resonance spectroscopy (1H-MRS) in regions with high BDNF levels
      (anterior cingulate cortex [ACC], left hippocampus). Relationship between BDNF
      concentration and brain metabolites was studied in linear regression analysis
      with BDNF concentration as dependent variable and metabolite concentrations, age,
      and gender as predictor variables. RESULTS: The BDNF serum concentrations were
      positively associated with the concentrations of NAA (T = 2.193, p = .037) and
      total choline (T = 1.997, p = .055; trend) but not total creatine or glutamate in
      the ACC. No significant association was observed between BDNF serum concentration
      and absolute metabolite concentrations in the hippocampus. CONCLUSIONS: The
      preliminary data might indicate that BDNF serum concentration reflects some
      aspects of neuronal plasticity as indicated by its association with NAA level in
      the cerebral cortex. The results would be in line with the notion that BDNF plays
      a central role in the regulation of neuronal survival and differentiation in the
      human brain.

PMID- 17560557
TI  - Regional dissection and determination of loosely bound and non-heme iron in the
      developing mouse brain.
AB  - Iron is a trace metal essential for normal brain development but toxic in excess
      as it is capable of generating highly reactive radicals that damage cells and
      tissue. Iron is stringently regulated by the iron regulatory proteins, IRP1 and
      IRP2, which regulate proteins involved in iron homeostasis at the
      posttranscriptional level. In this study, 12 distinct regions were microdissected
      from the mouse brain and regional changes in the levels of loosely bound and non
      heme iron that occur with development were measured. We examined 6, 12, and 24
      week old wildtype C57BL/6 mice and mice with a targeted deletion of iron
      regulatory protein 2 (IRP2-/-) that have been reported to develop
      neurodegenerative symptoms in adulthood. In wildtype mice, levels of loosely
      bound iron decreased while non-heme iron increased with development. In contrast,
      an increase in loosely bound and a more pronounced increase in non-heme iron was
      seen in IRP2-/- mice between 6 and 12 weeks of age, stemming from lower levels at
      6 weeks (the youngest age examined) compared to wildtype. These results have
      implications for understanding the increase in regional brain iron that is
      associated with normal aging and is postulated to be exacerbated in
      neurodegenerative disorders.

PMID- 17560558
TI  - Clock gene expression in the rat retina: effects of lighting conditions and
      photoreceptor degeneration.
AB  - Previous studies have shown that, in the Royal College of Surgeon rat, circadian
      rhythms in the retinal dopaminergic and melatonergic systems are still present
      after the photoreceptors have degenerated, thus demonstrating that circadian
      rhythmicity in the mammalian retina can be generated independently from the
      photoreceptors. The aim of the present study was to investigate the pattern of
      expression of the clock genes in the retina of the Royal College of Surgeons rat
      under different lighting conditions. Expression of clock genes was investigated
      in the retina of normal and dystrophic Royal College of Surgeons rats under 12 h
      of light/12 h of dark (LD), constant darkness (DD) and constant light (LL) using
      Real Time Quantitative RT-PCR. Our data indicate that, in control animals,
      Period1, Period2, Cryptochrome1, Cryptochrome2, Clock, Rora, Rev-Erb alpha and
      Npas2 mRNA levels showed a significant variation over the sampling period in LD
      cycles and in DD, whereas Bmal1 mRNA did not show any significant variation. In
      LL, the transcripts for Per1, Per2, Clock and Rev-Erb alpha showed significant
      temporal variations. In the dystrophic retina, only Per1 and Per2 mRNA levels
      showed a temporal variation over the 20-h period. Our work indicates that
      degeneration of the photoreceptor cells dramatically affected the expression
      levels and patterns of many clock genes. Finally, the present study suggests that
      investigating the expression pattern of clock genes using the whole retina or
      animals with photoreceptor degeneration may not provide any definitive answers
      about the working of the retinal circadian clock system.

PMID- 17560559
TI  - Bone marrow-derived multidrug resistance protein ABCB4 protects against
      atherosclerotic lesion development in LDL receptor knockout mice.
AB  - OBJECTIVE: Several members of the ATP binding cassette (ABC)-transporter super
      family expressed in macrophages protect against atherosclerosis by promoting
      macrophage cholesterol and phospholipid efflux. Systemic disruption of ABCB4 in
      mice results in a virtual absence of phospholipids in bile and a strongly
      impaired biliary cholesterol secretion, indicating that ABCB4 plays an essential
      role in cellular lipid efflux. The aim of the current study was to determine the
      role of bone marrow-derived ABCB4 in atherosclerotic lesion development. METHODS:
      Chimeras were created that specifically lack ABCB4 in bone marrow-derived cells,
      including macrophages, by performing a bone marrow transplantation on LDL
      receptor knockout (LDLr-/-) mice. Atherosclerotic lesion development was induced
      by feeding a high-cholesterol diet (15% fat and 0.25% cholesterol). RESULTS:
      Serum cholesterol levels were significantly lower in mice reconstituted with
      ABCB4 knockout bone marrow as a result of reduced VLDL and LDL cholesterol
      levels. Despite the lower serum cholesterol levels, ABCB4 deficiency in bone
      marrow-derived cells resulted in a 1.8-fold (p=0.005) increase in lesion size. In
      vitro foam cell formation, induced with acetylated LDL (AcLDL) in peritoneal
      macrophages, was increased in the absence of ABCB4, possibly due to a 2-fold
      (p<0.05) increased association of AcLDL, while the efflux of cholesterol was
      unaffected. CONCLUSION: Bone marrow-derived ABCB4 has an important anti
      atherosclerotic function, probably by limiting macrophage foam cell formation.

PMID- 17560560
TI  - Characterization of a novel and potent collagen antagonist, caffeic acid
      phenethyl ester, in human platelets: in vitro and in vivo studies.
AB  - OBJECTIVE: Caffeic acid phenethyl ester (CAPE), which is derived from the
      propolis of honeybee hives, has been demonstrated to possess multiple
      pharmacological activities. In the present study, CAPE (6-25 microM) specifically
      inhibited collagen-induced platelet aggregation and the ATP release reaction in
      platelet suspensions. METHODS: Platelet aggregation, flow cytometric analysis,
      immunoblotting, and electron spin resonance (ESR) were used to assess the anti
      platelet activity of CAPE. Fluorescein sodium-induced platelet thrombi in
      mesenteric microvessels of mice were used for an in vivo study. RESULTS: CAPE (15
      100 microM) produced a concentration-related rightward displacement of the
      collagen concentration-response curve, and the Schild plot gave pA(2) and pA(10)
      values of 4.28+/-0.07 and 3.14+/-0.73, respectively, with a slope of -0.83+/
      0.16, indicating specific antagonism. CAPE (25 microM) also inhibited platelet
      aggregation stimulated by the glycoprotein VI agonist, convulxin, and the
      alpha(2)beta(1) integrin agonist, aggretin. CAPE (25 microM) also markedly
      interfered with FITC-collagen binding to platelet membranes. CAPE (15 and 25
      microM) concentration-dependently inhibited collagen-induced platelet activation
      accompanied by [Ca(+2)](i) mobilization, phosphoinositide breakdown, activation
      of protein kinase C and mitogen-activated protein kinases (i.e., ERK2, JNK, and
      p38 MAPK), Akt phosphorylation, and thromboxane A(2) formation. In the ESR study,
      CAPE (15 and 25 microM) markedly reduced hydroxyl radical (OH) formation in
      collagen-activated platelets. In an in vivo study, CAPE (5 mg/kg) significantly
      prolonged the latency in inducing platelet plug formation in mesenteric venules
      of mice. CONCLUSIONS: The most important findings of this study suggest that CAPE
      specifically inhibits collagen-induced platelet activation. Thus, CAPE treatment
      may represent a novel approach to lowering the risk of or improving function in
      thromboembolism-related disorders.

PMID- 17560561
TI  - Global gene expression profiling reveals similarities and differences among mouse
      pluripotent stem cells of different origins and strains.
AB  - Pluripotent stem cell lines with similar phenotypes can be derived from both
      blastocysts (embryonic stem cells, ESC) and primordial germ cells (embryonic germ
      cells, EGC). Here, we present a compendium DNA microarray analysis of multiple
      mouse ESCs and EGCs from different genetic backgrounds (strains 129 and C57BL/6)
      cultured under standard conditions and in differentiation-promoting conditions by
      the withdrawal of Leukemia Inhibitory Factor (LIF) or treatment with retinoic
      acid (RA). All pluripotent cell lines showed similar gene expression patterns,
      which separated them clearly from other tissue stem cells with lower
      developmental potency. Differences between pluripotent lines derived from
      different sources (ESC vs. EGC) were smaller than differences between lines
      derived from different mouse strains (129 vs. C57BL/6). Even in the
      differentiation-promoting conditions, these pluripotent cells showed the same
      general trends of gene expression changes regardless of their origin and genetic
      background. These data indicate that ESCs and EGCs are indistinguishable based on
      global gene expression patterns alone. On the other hand, a detailed comparison
      between a group of ESC lines and a group of EGC lines identified 20 signature
      genes whose average expression levels were consistently higher in ESC lines, and
      84 signature genes whose average expression levels were consistently higher in
      EGC lines, irrespective of mouse strains. Similar analysis identified 250
      signature genes whose average expression levels were consistently higher in a
      group of 129 cell lines, and 337 signature genes whose average expression levels
      were consistently higher in a group of C57BL/6 cell lines. Although none of the
      genes was exclusively expressed in either ESCs versus EGCs or 129 versus C57BL/6,
      in combination these signature genes provide a reliable separation and
      identification of each cell type. Differentiation-promoting conditions also
      revealed some minor differences between the cell lines. For example, in the
      presence of RA, EGCs showed a lower expression of muscle- and cardiac-related
      genes and a higher expression of gonad-related genes than ESCs. Taken together,
      the results provide a rich source of information about the similarities and
      differences between ESCs and EGCs as well as 129 lines and C57BL/6 lines. Such
      information will be crucial to our understanding of pluripotent stem cells. The
      results also underscore the importance of studying multiple cell lines from
      different strains when making comparisons based on gene expression analysis.

PMID- 17560562
TI  - The retinal ganglion cell axon's journey: insights into molecular mechanisms of
      axon guidance.
AB  - The developing visual system has proven to be one of the most informative models
      for studying axon guidance decisions. The pathway is composed of the axons of a
      single neuronal cell type, the retinal ganglion cell (RGC), that navigate through
      a series of intermediate targets on route to their final destination. The
      molecular basis of optic pathway development is beginning to be elucidated with
      cues such as netrins, Slits and ephrins playing a key role. Other factors best
      characterised for their role as morphogens in patterning developing tissues, such
      as sonic hedgehog (Shh) and Wnts, also act directly on RGC axons to influence
      guidance decisions. The transcriptional basis of the spatial-temporal expression
      of guidance cues and their cognate receptors within the developing optic pathway
      as well as mechanisms underlying the plasticity of guidance responses also are
      starting to be understood. This review will focus on our current understanding of
      the molecular mechanisms directing the early development of functional
      connections in the developing visual system and the insights these studies have
      provided into general mechanisms of axon guidance.

PMID- 17560563
TI  - Fgf10 dosage is critical for the amplification of epithelial cell progenitors and
      for the formation of multiple mesenchymal lineages during lung development.
AB  - The key role played by Fgf10 during early lung development is clearly illustrated
      in Fgf10 knockout mice, which exhibit lung agenesis. However, Fgf10 is
      continuously expressed throughout lung development suggesting extended as well as
      additional roles for FGF10 at later stages of lung organogenesis. We previously
      reported that the enhancer trap Mlcv1v-nLacZ-24 transgenic mouse strain functions
      as a reporter for Fgf10 expression and displays decreased endogenous Fgf10
      expression. In this paper, we have generated an allelic series to determine the
      impact of Fgf10 dosage on lung development. We report that 80% of the newborn
      Fgf10 hypomorphic mice die within 24 h of birth due to respiratory failure. These
      mutant mouse lungs display severe hypoplasia, dilation of the distal airways and
      large hemorrhagic areas. Epithelial differentiation and proliferation studies
      indicate a specific decrease in TTF1 and SP-B expressing cells correlating with
      reduced epithelial cell proliferation and associated with a decrease in
      activation of the canonical Wnt signaling in the epithelium. Analysis of vascular
      development shows a reduction in PECAM expression at E14.5, which is associated
      with a simplification of the vascular tree at E18.5. We also show a decrease in
      alpha-SMA expression in the respiratory airway suggesting defective smooth muscle
      cell formation. At the molecular level, these defects are associated with
      decrease in Vegfa and Pdgfa expression likely resulting from the decrease of the
      epithelial/mesenchymal ratio in the Fgf10 hypomorphic lungs. Thus, our results
      indicate that FGF10 plays a pivotal role in maintaining epithelial progenitor
      cell proliferation as well as coordinating alveolar smooth muscle cell formation
      and vascular development.

PMID- 17560564
TI  - Guanylate cyclase and cyclic GMP-dependent protein kinase regulate agrin
      signaling at the developing neuromuscular junction.
AB  - During formation of the neuromuscular junction (NMJ), agrin secreted by motor
      axons signals the embryonic muscle cells to organize a postsynaptic apparatus
      including a dense aggregate of acetylcholine receptors (AChRs). Agrin signaling
      at the embryonic NMJ requires the activity of nitric oxide synthase (NOS). Common
      downstream effectors of NOS are guanylate cyclase (GC), which synthesizes cyclic
      GMP, and cyclic GMP-dependent protein kinase (PKG). Here we show that GC and PKG
      are important for agrin signaling at the embryonic NMJ of the frog, Xenopus
      laevis. Inhibitors of both GC and PKG reduced endogenous AChR aggregation in
      embryonic muscles by 50-85%, and blocked agrin-induced AChR aggregation in
      cultured embryonic muscle cells. A cyclic GMP analog, 8-bromo-cyclic GMP,
      increased endogenous AChR aggregation in embryonic muscles to 3- to 4-fold
      control levels. Overexpression of either GC or PKG in embryos increased AChR
      aggregate area by 60-170%, whereas expression of a dominant negative form of GC
      inhibited endogenous aggregation by 50%. These results indicate that agrin
      signaling in embryonic muscle cells requires the activity of GC and PKG as well
      as NOS.

PMID- 17560565
TI  - Zn mobility and geochemistry in surface sulfide mining soils from SE Spain.
AB  - The extraction of metallic minerals and the mineral dressing operations in
      concentrators produced a high impact in soils and sediments. Heavy metals in
      soils constitute a high risk of pollution, not only for mining areas, but also
      for agriculture and villages placed in subsidiary areas. This research has been
      focused on the assessment of the real environmental and health hazards of Zn in
      relation to geochemistry and metal mobility in surface soils from a mining area
      in SE Spain, under semiarid weather conditions. Mineralogy of the studied soils
      revealed major presence of quartz, but also of other silicates, sulfates,
      carbonates, and sulfides. Regarding Zn minerals, the presence of sphalerite as
      the main Zn sulfide, and of goslarite as Zn sulfate, and of smithsonite as Zn
      carbonate should be highlighted. Soil pH ranged between 4.4 and 4.9 and the
      electrical conductivity between 55 and 85 microS/cm. By using the sequential
      extraction procedure, the achieved results show that zinc is not only mainly
      associated to primary but also to secondary sulfides. Total concentration of the
      non-available fractions rises up to 98.45% of total Zn in the studied soils. On
      the other hand, available Zn fraction did not exceed more than 1.55% in
      percentage and less than 2000 ppm in absolute terms, and when referred to more
      easily available fraction (water-soluble and exchangeable fractions), these
      values are not more than 0.44% and then 800 ppm. Therefore, although there is a
      significant pollution level in this area, immediate hazard for the environment
      can be assessed as moderate. Finally it should be highlighted that these surface
      soils have undergone concentration processes of sphalerite, whose mechanisms
      should be related to the ascending flow of capillary water and the dragging of
      sphalerite crystals and Zn salts by electrokinetic and colloidal processes These
      processes seem to occur based on environmental pollution by wind and water
      erosion, and therefore directly associated to environmental pollution and risks
      by free metals.

PMID- 17560566
TI  - Ouabain augments and maintains the catecholamine release responses evoked by
      repetitive pulses of potassium, caffeine or histamine in perifused bovine
      chromaffin cells.
AB  - Cardiac glycosides such as ouabain augment the release of neurotransmitters and
      hormones from various organs, tissues and cell systems. Here we have investigated
      novel aspects of the ouabain effects on fast-perifused bovine adrenal chromaffin
      cells subjected to repetitive stimulation during long-time periods with
      secretagogues that enhance Ca(2+) entry (i.e. 100 mM K(+)solution) or causing the
      release into the cytosol of the Ca(2+) stored in the endoplasmic reticulum (i.e.
      20 mM caffeine or 100 microM histamine). After 1 h of intermittent stimulation,
      the amperometrically measured catecholamine release responses decayed to 50% with
      K(+) pulses, and to 10-15% with caffeine or histamine pulses. Ouabain (10 microM)
      augmented 2-fold the K(+) secretory responses and kept them high, along an hour.
      When given after the responses had decayed upon repetitive caffeine or histamine
      pulsing, ouabain gradually restored such responses to their initial control
      values. On the basis of these results, we raise the hypothesis that ouabain may
      facilitate the handling by the cell of the endoplasmic reticulum Ca(2+) fluxes
      that are known to be involved in secretory vesicle transport and the regulation
      of exocytosis. This may have physiological and pathological interest in the light
      of an endogenous ouabain steroid found in the adrenal cortex.

PMID- 17560567
TI  - Selective effects of diallyl disulfide, a sulfane sulfur precursor, in the liver
      and Ehrlich ascites tumor cells.
AB  - The present in vivo studies demonstrated that diallyl disulfide (DADS), occurring
      in garlic, elevated hepatic sulfane sulfur level and activities of gamma
      cystathionase and 3-mercaptopyruvate sulfotransferase in healthy mice but did not
      affect the hepatic glutathione level. DADS efficiently corrected the
      concentrations of glutathione and sulfane sulfur, and ameliorated gamma
      cystathionase activity that had been lowered in the livers of Ehrlich ascites
      tumor-bearing mice. In Ehrlich ascites tumor cells, diallyl disulfide did not
      alter bound sulfane sulfur level, sulfotransferases activity or glutathione
      level. These data indicate that this compound is capable of acting efficiently
      and selectively only in the liver and can be used for hepatoprotection during
      chemotherapy.

PMID- 17560568
TI  - Roles of axonal voltage-dependent ion channels in damaged peripheral nerves.
AB  - Ion channels are fundamental to the correct functioning of nerves. A high density
      of Na(v) channels at nodes of Ranvier is crucial for generating sufficient local
      current to initiate a self-regenerating action potential. K(v)7 (KCNQ) channels
      are also functional components of nodes of Ranvier and contribute to the
      repolarization of the action potential. Paranodes underlying the paranodal loops
      have no channels whereas K(v)1.1 and K(v)1.2 channels cluster at juxtaparanodes.
      The disruption of the normal balance of different channels causes the
      inappropriate nerve activity that underlies a variety of nervous system diseases.
      Axonal voltage-dependent channels, nodal Na(v) and juxtaparanodal K(v) channels
      disperse after the nerve injury and reorganize with regeneration.

PMID- 17560569
TI  - Cooling augments vasoconstriction mediated by 5-HT1 and alpha2-adrenoceptors in
      the isolated equine digital vein: involvement of Rho kinase.
AB  - The vasculature of the equine digit fulfils an important role in
      thermoregulation. In other species, it has been found that cooling may enhance
      the response of cutaneous vessels to 5-hydroxytryptamine (5-HT) and alpha(2)
      adrenoceptor agonists. Translocation of alpha(2)-adrenoceptors to the smooth
      muscle cell membrane, mediated by Rho kinase, is thought to be involved in the
      cooling-enhanced response in mouse tail arteries. However, little is known about
      the effect of cooling on 5-HT receptor function. The present investigation
      compared the response of 5-bromo-6-(2-imidazolin-2-ylamino) quinoxaline
      (UK14304:1 nM to 30 microM), methoxamine (0.1 nM to 30 microM; in the presence of
      yohimbine 0.1 microM), 5-carboxamidotryptamine (5-CT; 0.1 nM to 10 microM) and
      alpha-methyl 5-HT (0.1 nM to 10 microM) in the isolated equine digital vein at 30
      degrees C and 22 degrees C. The effect of the Rho kinase inhibitor, fasudil (1
      microM), and the recovery of the response after the irreversible blockade of
      surface receptors with phenoxybenzamine (10 microM) or 2-ethoxy-1-ethoxycarbonyl
      1,2-dihydroquinoline (EEDQ;10 microM), was established. Moderate cooling
      significantly increased the maximum response to alpha-methyl 5-HT, 5-CT and
      UK14304 and shifted their response curves to the left. Cooling also augmented the
      phenoxybenzamine- and EEDQ-resistant response to UK14304 and 5-CT, respectively.
      Fasudil had no effect on the contractile response at 30 degrees C, but completely
      abrogated the effect of cooling on the response to 5-CT and UK14304. The response
      to methoxamine was not significantly affected by cooling. These results suggest
      that Rho kinase plays an important role in the cooling-enhanced response mediated
      by 5-HT(1B/D) receptors and alpha(2)-adrenoceptors. The exact mechanism by which
      Rho/Rho kinase enhances the functional responses mediated by these receptors in
      these vessels has yet to be determined.

PMID- 17560570
TI  - Dynamic changes in conjunctival dendritic cell numbers, anatomical position and
      phenotype during experimental allergic conjunctivitis.
AB  - Dendritic cells (DCs) are a subset of antigen-presenting cells (APCs) that are
      involved in the initiation and control of the immune response to antigens present
      at the interface with the environment. A limited number of groups have studied
      DCs in human and animal conjunctiva but no data is available concerning the
      different DC subsets present in the conjunctival tissue. The aims of this study
      are to characterize the phenotypes and numbers of DCs present in the murine model
      of allergic conjunctivitis using the technique of immunohistochemistry so as to
      aid the understanding of the mechanisms involved in allergic eye disease. A
      double immunofluorescence method was used to analyze the phenotypic distribution
      and density of DC subsets in the mouse conjunctival tissues of the allergic model
      using a panel of antibodies: CD11c, as a general marker of DCs, coupled with
      another DC subset marker such as Langerin for Langerhans cells (LCs), CD11b for
      myeloid DCs (mDCs) and mPDCA-1 for plasmacytoid DCs (pDCs). In the naive
      conjunctiva, mDCs were consistently detected in the subepithelial layer and
      substantia propria. In the epithelium and the subepithelial layer, very few LCs
      and virtually no pDCs were observed. Following allergen challenge, there was a
      marked influx of mDCs and pDCs, but no LCs, into the subepithelial layer and
      throughout the substantia propria. These results indicate that conjunctival DC
      subsets may play an important role in the immune-regulatory processes involved in
      the inflammatory component of allergic conjunctivitis.

PMID- 17560571
TI  - S100A7 (psoriasin) influences immune response genes in human breast cancer.
AB  - S100A7 (psoriasin) is highly expressed in preinvasive breast carcinomas and in a
      subset of poor prognosis invasive tumors. To determine the influence of S100A7
      expression on ERalpha negative breast cancer, we profiled mRNA gene expression by
      Microarray and SAGE analysis, using the ERalpha negative MDA-MB-231 cell line
      model. Statistically significant transcripts of genes with very high differential
      expression were further validated by QPCR in both MDA-MB-231 and MDA-MB-468 cell
      lines expressing exogenous and endogenous S100A7. S100A7 expression correlated
      with increases in genes associated with MHC class II receptor activity, antigen
      processing and antigen presentation, and immune cell activation. The
      transcription factors (TFs) prediction tool CARRIE confirmed an association
      between TFs reported to be upregulated by S100A7 (NF-kappaB, AP-1, and HIF1) and
      the regulation of many genes in this dataset. The relationship between S100A7 up
      regulation and the MHC class II and HLA-class II molecule coding gene CD74 was
      examined further in a cohort of ERalpha negative breast tumors by tissue
      microarray (TMA) and immunohistochemistry (IHC), confirming a significant
      association in vivo (p=0.042, n=149). These results are consistent with a role
      for S100A7 in modulating the immune response which may be a factor in early
      breast tumor progression.

PMID- 17560572
TI  - Normal or stress-induced fibroblast senescence involves COX-2 activity.
AB  - Cyclooxygenase-2 (COX-2) is an inducible enzyme of the prostaglandin biosynthesis
      pathway. It is involved in many stress responses, and its activity can produce
      oxidative damage, suggesting it could participate in senescence. In this study,
      COX-2 expression is shown to increase during senescence of normal human dermal or
      prostatic fibroblasts, and the ensuing prostaglandin E(2) (PGE(2)) production to
      increase about 10-fold. Enhancing this COX-2 activity by supplying exogenous
      arachidonic acid accelerates the occurrence of the major markers of senescence,
      cell-size increase, spreading, senescence-associated-beta-galactosidase (SA-beta
      Gal) activity and growth plateau. Conversely, blocking this COX-2 activity with
      the specific inhibitor NS398 partially inhibited the occurrence of these markers.
      COX-2 expression and PGE(2) production are also increased about 10-fold during
      both NF-kappaB- or H(2)O(2)-induced senescence. Using NS398 or small interferent
      RNA specifically targeting COX-2 attenuated the appearance of the SA-beta-Gal
      activity and growth arrest in both stress situations. Taken together, these
      findings indicate that COX-2 is highly up-regulated during both normal and stress
      induced fibroblast senescence and contributes to the establishment of the
      senescent characteristics.

PMID- 17560573
TI  - The neurocytokine, interleukin-6, corrects nerve dysfunction in experimental
      diabetes.
AB  - Interleukin-6 (IL-6) is a member of the neuropoietic cytokine family and has a
      multifunctional biological role in regulating the immune response, acute phase
      reactions, and hematopoiesis. IL-6 is also important in neural development and
      has neurotrophic actions. The aim was to ascertain whether IL-6 treatment could
      rectify some of the adverse early changes in neurovascular function in
      streptozotocin-induced diabetic rats. After 4 weeks of untreated diabetes, rats
      were treated with IL-6 (1-10 microg/kg thrice weekly) for 4 weeks. Diabetes
      caused 22% and 22.5% reductions in sciatic nerve motor and saphenous nerve
      sensory conduction velocity, respectively, which were dose dependently corrected
      by treatment. Diabetic rats also showed thermal hyperalgesia and tactile
      allodynia, which were completely corrected by IL-6; however, IL-6 was ineffective
      against mechanical hyperalgesia. Sciatic nerve endoneurial perfusion was 42.2%
      reduced by diabetes and blood flow was returned to the nondiabetic range by 10
      microg/kg IL-6 treatment. The ED(50) values for these actions ranged from 1.2
      microg/kg for sensory conduction velocity to 3.2 microg/kg for sciatic nerve
      perfusion. Thus, IL-6 treatment improved several measures of nerve dysfunction in
      experimental diabetes, and these effects correlated with a recovery of nerve
      blood flow. The magnitude of these beneficial effects and the potential joint
      neurotrophic and vascular action suggests that IL-6 could be a candidate for
      further evaluation in clinical trials of diabetic neuropathy.

PMID- 17560574
TI  - Effects of Hoechst 33342 on C2C12 and PC12 cell differentiation.
AB  - Accumulative evidence demonstrates that normal as well as cancer stem cells can
      be identified as a side population following Hoechst 33342 staining and flow
      cytometric analysis. This popular method is based on the ability of stem cells to
      efflux this fluorescent vital dye. We demonstrate that Hoechst 33342 can affect
      cell differentiation, suggesting potential complications in the interpretation of
      data.

PMID- 17560575
TI  - Putative spermine synthases from Thalassiosira pseudonana and Arabidopsis
      thaliana synthesize thermospermine rather than spermine.
AB  - Polyamines are involved in many fundamental cellular processes. Common polyamines
      are putrescine, spermidine and spermine. Spermine is synthesized by transfer of
      an aminopropyl residue derived from decarboxylated S-adenosylmethionine to
      spermidine. Thermospermine is an isomer of spermine and assumed to be synthesized
      by an analogous mechanism. However, none of the recently described spermine
      synthases was investigated for their possible activity as thermospermine
      synthases. In this work, putative spermine synthases from the diatom
      Thalassiosira pseudonana and from Arabidopsis thaliana could be identified as
      thermospermine synthases. These findings may explain the previous result that two
      putative spermine synthase genes in Arabidopsis produce completely different
      phenotypes in knock-out experiments. Likely, part of putative spermine synthases
      identifiable by sequence comparisons represents in fact thermospermine synthases.

PMID- 17560576
TI  - GSK-3beta mediates in the progesterone inhibition of estrogen induced cyclin D2
      nuclear localization and cell proliferation in cyclin D1-/- mouse uterine
      epithelium.
AB  - We report that glycogen synthase kinase (GSK)-3beta is phosphorylated at ser9 and
      inactivated in uterine epithelial cells from E(2)-treated cyclin D1 null mutant
      mice. Simultaneous administration of P(4) together with E(2) blocked this effect.
      Pharmacological inhibition of GSK-3beta activity in mice treated with P(4)E(2)
      reversed the nuclear exclusion of cyclin D2 in the uterine epithelial cells and
      this caused phosphorylation of Rb protein and progression of cells towards S
      phase. Our results indicate that GSK-3beta is a major target of E(2) and P(4) in
      regulation of cyclin D2 localization in the mouse uterine epithelium.

PMID- 17560577
TI  - Identification of the amino acids crucial for the activities of drought
      responsive element binding factors (DREBs) of Brassica napus.
AB  - We have previously identified two homologous groups of BnDREBs in Brassica napus,
      the trans-active BnDREBI and the trans-inactive BnDREBII, which provided an ideal
      system to study the trans-activation of DREB1/CBF. Deletion analysis indicated
      that the two additional regions in BnDREBI contributed little to the
      transcriptional activity. Domain swapping analysis indicated that all the domains
      contributed to the activity of BnDREBI, including the ERF/AP2 DNA binding domain.
      Through site-directed mutagenesis, we identified nine residues that were involved
      in the activity of BnDREBI, among which six residues are specific to BnDREBI, and
      three are common to DREB1A.

PMID- 17560578
TI  - Creating new meaning or massaging old texts? Commentary on Rudolfsson et al.
      (2007), "The expression of caring within the perioperative dialogue: a
      hermeneutic study".

PMID- 17560579
TI  - POPC/apoA-I discs as a potent lipoprotein modulator in Tangier disease.
AB  - Tangier disease (TD) is a rare familial disorder with mutations in the ATP
      binding cassette transporter A1 (ABCA1) gene. It results in extremely low levels
      of HDL cholesterol. Since TD is a genetic disorder, a therapeutic approach to TD
      has not been established. We report a typical case of TD with a homozygous novel
      point mutation in the ABCA1 gene by using genomic DNA sequencing. Primary
      monocyte-derived macrophages of blood from a patient with TD and normolipidemic
      subjects were compared for cholesterol efflux. The macrophages from the TD
      patient showed no apoA-I-mediated cholesterol efflux. In contrast, POPC/apoA-I
      discs were able to take up cholesterol from macrophages from both the TD and
      normolipidemic subject. Capillary isotachophoresis (cITP), which separates
      lipoprotein into subfractions according to electrophoretic mobility, was used to
      characterize plasma lipoprotein subfractions. Both slow-migrating HDL (sHDL) and
      slow-migrating LDL (sLDL; unmodified LDL) subfractions were extremely low in the
      patient with TD. After incubation of plasma from the TD patient with POPC/apoA-I
      discs, sHDL and sLDL subfractions rapidly appeared. In conclusion, POPC/apoA-I
      discs not only have beneficial effects on cholesterol efflux, but also have
      potential as a lipoprotein modulator in patients with TD.

PMID- 17560580
TI  - Markers of endothelial dysfunction and low-grade inflammation are associated in
      the offspring of type 2 diabetic subjects.
AB  - The offspring of type 2 diabetic patients are at elevated risk for type 2
      diabetes and cardiovascular disease. The aim of our study was to characterize the
      role of various biomarkers of endothelial activation in a cohort of offspring of
      type 2 diabetic subjects and to assess the association of adhesion molecules with
      inflammatory markers and metabolic parameters. Cytokine and adhesion molecule
      levels were measured in 19 healthy subjects and in 129 offspring of patients with
      type 2 diabetes (109 with normal glucose tolerance and 20 with impaired glucose
      tolerance). Insulin sensitivity was determined with the hyperinsulinemic
      euglycemic clamp, insulin secretion with the intravenous glucose tolerance test,
      and abdominal fat distribution with computed tomography. The levels of vascular
      cell adhesion molecule-1, intercellular adhesion molecule-1, E-Selectin and
      vascular adhesion protein-1 were not increased in offspring of type 2 diabetic
      subjects, but they correlated with inflammatory markers (C-reactive protein,
      tumor necrosis-alpha, interleukin-6, interleukin-1 beta, interleukin-1 receptor
      antagonist, interleukin-8, interleukin-10 and interleukin-18). In conclusion, the
      levels of adhesion molecules were not elevated in the prediabetic state.
      Inflammatory markers and adhesion molecules were correlated suggesting that low
      grade inflammation may precede the elevation of levels of adhesion molecules.

PMID- 17560581
TI  - Effects of freezing rates and dimethyl sulfoxide concentrations on thermal
      expansion of rabbit aorta during freezing phase change as measured by thermo
      mechanical analysis.
AB  - Thermal expansion data are essential for thermal stress analysis in order to
      predict the likelihood of fracture formation in tissues during cryopreservation
      as well as cryosurgery. The current study focuses on examining the thermal
      expansion behavior of rabbit aorta during freezing, especially phase change
      processes. Thermo mechanical analysis (TMA) was used to investigate the effects
      of different concentrations of dimethyl sulfoxide (DMSO) cryoprotective agent
      (CPA) (0%, 5%, 10%, and 15% (v/v) DMSO) and different freezing rates (3, 5 and 10
      degrees C/min). The results showed that (1) the maximum of thermal strain for 10
      degrees C/min was approximately four times greater than that for 3 degrees C/min,
      and 1.4 times greater than that for 5 degrees C/min, and the higher the freezing
      rate, the larger the corresponding thermal expansion coefficient; (2) the maximum
      thermal strain of sample permeated by 5% DMSO approached that of 0% DMSO (i.e.,
      no DMSO was added); however, it showed very significant difference from that of
      15% DMSO (only half of that with 5% DMSO), and the thermal expansion coefficient
      decreased when the concentration of DMSO solution increased; (3) comparison with
      data available from the literature and with theoretically calculated values
      illustrated that the thermal expansion change was not equal to the volume change
      from free water to ice during freezing, but was related to the freezing rate of
      samples and the DMSO concentration.

PMID- 17560582
TI  - Patterns of protein adsorption in chromatographic particles visualized by optical
      microscopy.
AB  - A new method is presented to image transient patterns of protein adsorption in
      individual spherical chromatographic particles under strong binding conditions.
      The method takes advantage of the difference in refractive index between the
      protein-free and protein-saturated adsorbent matrix. When the particles are
      viewed with an ordinary microscope using white light illumination, the adsorption
      front appears as a bright ring that moves in time from the surface of the
      particle to its center. Experimental data are obtained for the proteins lysozyme
      and albumin with a commercial agarose-based cation exchanger. Sharp rings are
      observed in both cases confirming that protein mass transfer within the particles
      occurs via a shell-progressive diffusion mechanism. Quantitative analysis based
      on the shrinking core model provides an accurate and precise way of determining
      the intraparticle diffusivity for individual particles as a function of protein
      concentration and mobile phase composition.

PMID- 17560583
TI  - Capillary electrophoresis-mass spectrometry for the analysis of intact proteins.
AB  - Developments in the fields of protein chemistry, proteomics and biotechnology
      have increased the demand for suitable analytical techniques for the analysis of
      intact proteins. In 1989, capillary electrophoresis (CE) was combined with mass
      spectrometry (MS) for the first time and its potential usefulness for the
      analysis of intact (i.e. non-digested) proteins was shown. This article provides
      an overview of the applications of CE-MS within the field of intact protein
      analysis. The principles of the applied CE modes and ionization techniques used
      for CE-MS of intact proteins are shortly described. It is shown that separations
      are predominantly carried out by capillary zone electrophoresis and capillary
      isoelectric focusing, whereas electrospray ionization (ESI) and matrix-assisted
      laser desorption ionization (MALDI) are the most popular ionization techniques
      used for interfacing. The combination of CE with inductively coupled plasma (ICP)
      MS for the analysis of metalloproteins is also discussed. The various CE-MS
      combinations are systematically outlined and tables provide extensive overviews
      of the applications of each technique for intact protein analysis. Selected
      examples are given to illustrate the usefulness of the CE-MS techniques. Examples
      include protein isoform assignment, single cell analysis, metalloprotein
      characterization, proteomics and biomarker screening. Finally, chip-based
      electrophoresis combined with MS is shortly treated and some of its applications
      are described. It is concluded that CE-MS represents a powerful tool for the
      analysis of intact proteins yielding unique separations and information.

PMID- 17560584
TI  - A new algorithm of piecewise automated beam search for peak alignment of
      chromatographic fingerprints.
AB  - The alignment of chromatographic signals is an important preprocessing step
      before further multivariate analysis. This paper presents a method, automated
      peak alignment by beam search (Auto-PABS), to solve the problem of peak shift in
      chemical chromatographic fingerprints by piecewise shifting and linearly
      interpolating. It is characterized by searching an adaptive range for the values
      of shifting and linearly interpolating of each segment. This search range is
      estimated by the calculation of fast Fourier transform cross correlation between
      the sample segment and its corresponding reference segment. Thus, arbitrary peak
      alignment is avoided when the real peak shifts are unknown in a large data set.
      Since the maximum of search range is close to the real shift, more accurate beam
      search is adopted to accomplish the optimization process. Simulated data and
      herbal medicine fingerprints of HPLC and GC are selected for evaluation. The
      output matrix of aligned chromatographic profiles is used directly for principal
      components analysis, yielding satisfactory results on real samples.

PMID- 17560585
TI  - Evaluation of atmospheric pressure ionization interfaces for quantitative
      measurement of sulfonamides in honey using isotope dilution liquid chromatography
      coupled with tandem mass spectrometry techniques.
AB  - A comparison was made between electrospray, atmospheric pressure chemical and
      atmospheric pressure photospray ionizations to evaluate the MS/MS responses of
      standard sulfonamides and honey spiked samples. The sample preparation entails an
      acidic hydrolysis followed by a liquid/liquid extraction. Full method validation
      was realised by LC-APPI-MS/MS. Decision limit and detection capability were
      calculated for each analyte (at 50 microg/kg) and ranged between 53.6 and 56.9
      and 57.5 and 63.2 microg/kg, respectively. Limits of detection and of
      quantification ranged, respectively, at 0.4-4.5 and 1.2-15.0 microg/kg. Precursor
      ion scan experiments of m/z 92 were also carried out as a survey experiment,
      linked with an enhanced product ion scan experiment to potentially identified
      additional sulfonamides via a library search.

PMID- 17560586
TI  - Estimation of recovery by multistep purge-and-trap gas chromatographic-mass
      spectrometric analysis of honey volatiles.
AB  - Calculation of volatile recovery in dynamic headspace techniques such as purge
      and-trap (P&T) usually requires a calibration with standard compounds. When these
      are not available, application of mathematical models to the results obtained by
      multistep fractionation of a sample can be used for the estimation of recovery. A
      comparison of the fit quality of quantitative data (GC peak areas) using
      different calculation procedures and of the results of recovery estimation is
      presented for different honey volatiles. While models M1-M3 and M5 proposed in
      this paper correctly describe multistep experimental data for most honey
      compounds, other volatiles present a recovery behaviour which requires an
      additional parameter to be considered (models M4 and M6). For the last compounds,
      recovery is variable along the multistep procedure and the total amount cannot be
      accurately estimated by the use of multistep P&T fractionation.

PMID- 17560587
TI  - The hydrolysis of unsubstituted N-acylhomoserine lactones to their homoserine
      metabolites. Analytical approaches using ultra performance liquid chromatography.
AB  - Derivatives of N-acylhomoserine lactones (HSLs) with different alkanoyl side
      chains occur as quorum or diffusion sensing molecules in gram-negative bacteria
      and their quantitative chemical analysis became important as a possible way to
      follow regulation processes of their pathogenicity towards plants and animals.
      The lactone-ring of HSLs is chemically and biologically not stable: the
      corresponding serines can be formed in alkaline conditions and these may
      presumably behave inactive for the biological system. A fast and MS compatible
      liquid chromatographic method applying high pressure (ultra performance liquid
      chromatography) with diode array detection was optimized for the rapid
      quantitative determination of HSLs and their corresponding hydrolysis products.
      The technique was used to follow and model the hydrolysis reactions of HSLs as
      function of pH under controlled conditions. Moreover, the method could be
      triggered to allow a confirmation in the assignment of the potential HSLs in real
      samples by analysis of the real samples before and after hydrolysis. Quantitative
      performance characteristics and the character of the hydrolysis reaction were
      studied as well. The optimized method was successfully applied to a bacterial
      culture supernatant real sample containing HSLs.

PMID- 17560588
TI  - Separation and determination of amino acids by micellar electrokinetic
      chromatography coupling with novel multiphoton excited fluorescence detection.
AB  - In this article, it was demonstrated that separation and determination of 20
      amino acids were accomplished by micellar electrokinetic chromatography (MEKC)
      coupling with novel multiphoton excited fluorescence (MPEF) detection method.
      Different from MPEF achieved by expensive fs laser, continuous wave (CW) diode
      laser of ultra-low cost was uniquely employed in our MPEF system. Amino acids
      were fluorescently labeled with fluorescein isothiocyanate (FITC), and were
      subjected to sodium dodecyl sulfate (SDS)-based MEKC separation and CW-based MPEF
      detection. The result was compared with that by single photon excited
      fluorescence (SPEF), which indicated that MPEF had the advantages of better mass
      detectability and higher separation selectivity over SPEF. Quantitative analysis
      was performed and revealed linear dynamic range of over 2 orders of magnitude,
      with mass detection limit down to ymole level. To evaluate the reliability, this
      method was successfully applied for analyzing a commercial nutrition supplement
      liquid.

PMID- 17560589
TI  - Electrophoresis of soft particles at high electrolyte concentrations: an
      interpretation by the Henry theory.
AB  - The existence of electrophoretic mobility at high electrolyte concentrations
      defines a remarkable peculiarity in the electrosurface characteristics of soft
      particles. According to Ohshima [H. Ohshima, Colloids Surf. 103 (1995) 249], this
      effect is caused by the electroosmotic flow within the soft particle shell. An
      explanation supporting Ohshima's conclusion can be derived from classic
      electrokinetic theories. Based on the Henry theory [D.C. Henry, Proc. R. Soc.
      London Ser. A 133 (1931) 106], we demonstrate that the electrophoretic mobility
      of soft particles does not disappear at decinormal concentration.

PMID- 17560590
TI  - Translational and rotational dynamics of colloidal rods by direct visualization
      with confocal microscopy.
AB  - We report an experimental method to characterize the dynamics of colloidal rods
      by measuring their rotation and translation in three dimensions with confocal
      microscopy. The method relies on solvent viscosification to retard dynamics to
      time scales that are compatible with 3D confocal optical microscopy. Because the
      method yields a full three-dimensional characterization of rod displacement and
      orientation, it is applicable to situations in which complex, anisotropic
      dynamics emerge. Examples include behavior in liquid crystal phases with both
      orientational and positional order, suspensions subjected to applied fields such
      as shear flow or sedimentation, and the emerging area of anisotropic particle
      dynamics. We demonstrate the performance of the method by quantifying the
      Brownian motion of fluorescent poly(methyl methacrylate) rods (aspect ratio,
      L/D=3.1 and 7.0) grafted with poly(dimethylsiloxane) stabilizer. The rods are
      dispersed at dilute concentration in a solvent mixture of viscosity 2.0 Pa s. Rod
      translational and rotational diffusivities are extracted from the measured
      translational mean square displacement of the centroid positions and of the rod
      unit vector u(t), respectively. Rod orientational dynamics are characterized
      relative to both their azimuthal and polar angles. Probability distributions for
      the translation and rotation in the frame of rod are computed from the
      measurements. Experimental values obtained agree well with theory available for
      the dynamics of isolated rods.

PMID- 17560591
TI  - Immune system development in the dog and cat.
AB  - Routine vaccination of young puppies and kittens takes place within the first 16
      weeks of life, during which time there is considerable change in the immune
      system of these animals. Newborn pups and kittens must obtain passive immune
      protection through the ingestion of colostrum within the first hours of life. The
      timing of early life vaccination is determined by the period of time required for
      passively acquired immunoglobulin to degrade, thereby permitting an endogenous
      immune response to be generated by the neonate. In the absence of inhibitory
      maternally derived antibody (MDA), pups and kittens are capable of mounting a
      protective immune response at an early age. New generation molecular vaccines
      appear able to circumvent the inhibitory effects of MDA. In addition to changes
      in serum immunoglobulin concentrations, there are alterations in the numbers and
      proportions of blood and tissue leucocytes (particularly CD4(+) and CD8(+) T
      cells, and B cells) during the first year of life. The qualitative nature of the
      newborn immune system may also alter from Th2 regulation in utero to Th1
      regulation in the neonatal period. Immune function is likely to be genetically
      determined, and in dogs there is evidence for breed effects on immune function
      which likely relate to the inheritance of particular haplotypes of major
      histocompatibility complex (MHC) genes. The design of vaccines for young animals
      of these species must take into account these immunological changes and the
      potential modulatory effect of vaccines on immune development.

PMID- 17560592
TI  - Immunization of puppies in the presence of maternally derived antibodies against
      canine distemper virus.
AB  - Vaccination of dams with modified-live canine distemper virus (CDV) vaccines will
      elicit high concentrations of colostral antibody, that although vital for
      protection of the pup during the first weeks of life, can interfere with active
      vaccination against the virus. In the present study, 12 pups, 7-9 weeks of age,
      with maternally derived immunity to CDV, were vaccinated with a canarypox
      vectored CDV vaccine. These pups were protected against intravenous challenge
      with CDV. Three littermate pups that were unvaccinated all developed clinical
      signs of infection after challenge, and two of these control pups died.

PMID- 17560593
TI  - The nature and consequences of intra- and inter-vaccine interference.
AB  - Vaccine interference may be intra- or inter-vaccine in nature. Intra-vaccine
      interference is determined by the nature and dose of the individual vaccine
      valences, the nature and quality of any additives and the pharmaceutical
      formulation of the product. Additionally, vaccinee factors including the presence
      of pre-existing immunity, the stage of immunological maturation, genetic and
      environmental background may also determine interference. The vaccine schedule
      and mode of delivery are further contributory factors. In practice, the
      phenomenon of vaccine interference argues that individual vaccines should not be
      combined or associated in the absence of specific data sheet recommendations to
      do so.

PMID- 17560594
TI  - Use of a vectored vaccine against infectious bursal disease of chickens in the
      face of high-titred maternally derived antibody.
AB  - Interference by maternally derived antibody (MDA) is a major problem for the
      vaccination of young chickens against infectious bursal disease (IBD). The choice
      of the timing of vaccination and of the type (degree of attenuation) of modified
      live vaccine (MLV) to use is often difficult. An IBD vectored vaccine (vHVT13),
      in which turkey herpesvirus (HVT) is used as the vector, was recently developed.
      This vaccine is administered once at the hatchery, either in ovo or by the
      subcutaneous route, to 1-day-old chicks at a time when MDA is maximal. In terms
      of safety, the vHVT13 vaccine had negligible impact on the bursa of Fabricius
      when compared with classical IBD MLV. Vaccination and challenge studies
      demonstrated that this vaccine is able to protect chickens against various IBD
      virus (IBDV) challenge strains including very virulent, classical, and USA
      variant IBDV, despite the presence of high-titred IBD MDA at the time of
      vaccination. These data show that the vector vaccine combines a safety and
      efficacy profile that cannot be achieved with classical IBD vaccines.

PMID- 17560595
TI  - Alternative early life vaccination programs for companion animals.
AB  - An experimental challenge study of multicomponent vaccination of kittens is
      reported. Seven-to-nine week old, specific pathogen-free kittens received two
      injections (4 weeks apart) of non-adjuvanted, multicomponent vaccine formulated
      at the minimum protective dose. Kittens were challenged at 4 weeks or 1 year post
      vaccination with individual infectious agents. Vaccination induced complete
      protection against challenge from feline parvovirus on both occasions, but at 1
      year, the protection against feline herpesvirus, feline calicivirus and
      Chlamydophila felis was not as strong as 4 weeks after vaccination. This
      demonstration of a decline in protective immunity at the normal time of
      administration of the first booster vaccine suggests that earlier administration
      of this booster (at 4-6 months of age) may provide better protection. The effect
      of maternally derived antibody (MDA) on kitten vaccination was determined by
      conducting an identical experiment but with kittens born to queens vaccinated
      during pregnancy. Serum antibody titres to specific vaccine components were
      measured in these kittens on day 0 (time of first vaccination), day 28 (time of
      second vaccination) and day 42. There was heterogeneity in transfer of MDA to
      kittens within a litter, and between litters. MDA may neutralize the serological
      response of kittens on the first, and occasionally the second, occasion of
      vaccination when vaccination is performed at 8 and 12 weeks of age. This finding
      underpins recent recommendations that the final vaccination in the primary series
      be administered at 16 weeks of age.

PMID- 17560596
TI  - Eye movements during spoken word recognition in Russian children.
AB  - This study explores incremental processing in spoken word recognition in Russian
      5- and 6-year-olds and adults using free-viewing eye-tracking. Participants
      viewed scenes containing pictures of four familiar objects and clicked on a
      target embedded in a spoken instruction. In the cohort condition, two object
      names shared identical three-phoneme onsets. In the noncohort condition, all
      object names had unique onsets. Coarse-grain analyses of eye movements indicated
      that adults produced looks to the competitor on significantly more cohort trials
      than on noncohort trials, whereas children surprisingly failed to demonstrate
      cohort competition due to widespread exploratory eye movements across conditions.
      Fine-grain analyses, in contrast, showed a similar time course of eye movements
      across children and adults, but with cohort competition lingering more than 1s
      longer in children. The dissociation between coarse-grain and fine-grain eye
      movements indicates a need to consider multiple behavioral measures in making
      developmental comparisons in language processing.

PMID- 17560597
TI  - RNA interference suggests sulfakinins as satiety effectors in the cricket Gryllus
      bimaculatus.
AB  - In the Mediterranean field cricket, Gryllus bimaculatus, the action of sulfakinin
      (SK) gene expression on food intake, food transport in the gut and carbohydrate
      digestion (alpha-amylase activity) was investigated by using the RNA interference
      (RNAi) method. Injection of SK double-stranded (ds) RNA into the abdomen of
      female adults and last instar larvae led to a systemic silencing of the SK gene,
      as was shown by RT-PCR studies. In adults, suppression of SK gene expression was
      effective from the first day after injection up to at least the third day.
      Treatment of the adult crickets by injection or feeding of dsRNA led to a
      stimulation of the food intake. Assuming that the gene silencing is followed by a
      depletion of the SK in tissues and/or haemolymph implies an inhibitiory role of
      the native SK peptides on food intake. The alpha-amylase activity in vitro in the
      midgut tissue and in the secretions of adult females was not affected by
      silencing the SK gene.

PMID- 17560598
TI  - Simvastatin inhibits TNFalpha-induced invasion of human cardiac myofibroblasts
      via both MMP-9-dependent and -independent mechanisms.
AB  - Statins can reduce adverse myocardial remodeling independently of their
      cholesterol-lowering ability. We have previously reported that simvastatin
      inhibits tumor necrosis factor-alpha (TNFalpha)-induced cardiac myofibroblast
      invasion and MMP-9 secretion, key events in this remodeling process. The aim of
      the present study was to investigate the mechanisms underlying this effect.
      Selective MMP-9 gene silencing with siRNA oligonucleotides revealed that
      myofibroblast invasion through a Matrigel barrier (Boyden chamber assay) was MMP
      9-dependent. In contrast, cell migration (in the absence of Matrigel) was MMP-9
      independent. Simvastatin, a commonly prescribed statin, inhibited both invasion
      and migration of myofibroblasts and disrupted the actin cytoskeleton as
      determined by confocal microscopy of rhodamine-phalloidin staining. All these
      effects of simvastatin were mimicked by the Rho-kinase inhibitor Y27632. TNFalpha
      activated the ERK-1/2, p38 MAPK, PI-3-kinase and NF-kappaB pathways but not the
      JNK pathway, as determined by immunoblotting with phospho-specific antibodies.
      Quantitative RT-PCR revealed that TNFalpha-induced MMP-9 mRNA expression was
      substantially reduced by pharmacological inhibitors of the ERK-1/2, PI-3-kinase
      and NF-kappaB pathways. However, none of the signal transduction pathways studied
      was influenced by simvastatin treatment. Moreover, despite reducing MMP-9
      secretion, simvastatin had no effect on MMP-9 promoter activity (luciferase
      reporter assay) and actually increased MMP-9 mRNA levels. In summary, simvastatin
      reduces TNFalpha-induced invasion of human cardiac myofibroblasts through two
      distinct mechanisms: (i) by attenuating cell migration via Rho-kinase inhibition
      and subsequent cytoskeletal disruption, and (ii) by decreasing MMP-9 secretion
      via a post-transcriptional mechanism.

PMID- 17560599
TI  - Decreased phosphorylation levels of cardiac myosin-binding protein-C in human and
      experimental heart failure.
AB  - Cardiac myosin-binding protein-C (cMyBP-C) is an important regulator of cardiac
      contractility, and its phosphorylation by PKA is a mechanism that contributes to
      increased cardiac output in response to beta-adrenergic stimulation. It is
      presently unknown whether heart failure alters cMyBP-C phosphorylation. The
      present study determined the level of phosphorylated cMyBP-C in failing human
      hearts and in a canine model of pacing-induced heart failure. A polyclonal
      antibody directed against the major phosphorylation site of cMyBP-C (Ser-282) was
      generated and its specificity was confirmed by PKA phosphorylation with
      isoprenaline in cardiomyocytes and Langendorff-perfused mouse hearts. Left
      ventricular myocardial tissue from (i) patients with terminal heart failure (hHF;
      n=12) and nonfailing donor hearts (hNF; n=6) and (ii) dogs with rapid-pacing
      induced end-stage heart failure (dHF; n=10) and sham-operated controls (dNF;
      n=10) were used for quantification of total cMyBP-C and phospho-cMyBP-C by
      Western blotting. Total cMyBP-C protein levels were similar in hHF and hNF as
      well as in dHF and dNF. In contrast, the ratio of phospho-cMyBP-C to total cMyBP
      C levels were >50% reduced in hHF and >40% reduced in dHF. In summary, cMyBP-C
      phosphorylation levels are markedly decreased in human and experimental heart
      failure. Thus, the compromised contractile function of the failing heart might be
      in part attributable to reduced cMyBP-C phosphorylation levels.

PMID- 17560600
TI  - An improved system for the generation and analysis of mutant proteins containing
      unnatural amino acids in Saccharomyces cerevisiae.
AB  - We have previously described methodology that makes it possible to genetically
      encode a wide array of unnatural amino acids in both prokaryotic and eukaryotic
      organisms. Here, we report the systematic optimization of a Saccharomyces
      cerevisiae expression system for the production of mutant proteins containing
      unnatural amino acids. Modifications include significant increases in both the
      expression levels of the orthogonal Escherichia coli amber suppressor tRNA(CUA)
      and cognate aminoacyl-tRNA synthetase (aaRS) pair, and expression of the target
      protein gene using a strong transcriptional promoter, optimized codons and
      elevated plasmid copy numbers. With this new system, a number of unnatural amino
      acids, including the photocrosslinkers p-benzoylphenylalanine and p
      azidophenylalanine, and the chemically reactive amino acids, p
      acetylphenylalanine and p-propargyloxyphenylalanine, were incorporated into human
      superoxide dismutase (hSOD) in yeast in good yields (maximally approximately 6-8
      mg/l of culture in most cases). Mass spectrometric analysis of the hSOD mutants
      was performed with high dynamic range using multiple reaction monitoring that
      provided new insights into the factors that control the fidelity of unnatural
      amino acid incorporation.

PMID- 17560601
TI  - Plant hemoglobins: a molecular fossil record for the evolution of oxygen
      transport.
AB  - The evolution of oxygen transport hemoglobins occurred on at least two
      independent occasions. The earliest event led to myoglobin and red blood cell
      hemoglobin in animals. In plants, oxygen transport "leghemoglobins" evolved much
      more recently. In both events, pentacoordinate heme sites capable of inert oxygen
      transfer evolved from hexacoordinate hemoglobins that have unrelated functions.
      High sequence homology between hexacoordinate and pentacoordinate hemoglobins in
      plants has poised them for potential structural analysis leading to a molecular
      understanding of this important evolutionary event. However, the lack of a plant
      hexacoordinate hemoglobin structure in the exogenously ligand-bound form has
      prevented such comparison. Here we report the crystal structure of the cyanide
      bound hexacoordinate hemoglobin from barley. This presents the first opportunity
      to examine conformational changes in plant hexacoordinate hemoglobins upon
      exogenous ligand binding, and reveals structural mechanisms for stabilizing the
      high-energy pentacoordinate heme conformation critical to the evolution of
      reversible oxygen binding hemoglobins.

PMID- 17560602
TI  - Adenosine 5'-O-(3-thio)triphosphate (ATPgammaS) promotes positive supercoiling of
      DNA by T. maritima reverse gyrase.
AB  - Reverse gyrases are topoisomerases that catalyze ATP-dependent positive
      supercoiling of circular covalently closed DNA. They consist of an N-terminal
      helicase-like domain, fused to a C-terminal topoisomerase I-like domain. Most of
      our knowledge on reverse gyrase-mediated positive DNA supercoiling is based on
      studies of archaeal enzymes. To identify general and individual properties of
      reverse gyrases, we set out to characterize the reverse gyrase from a
      hyperthermophilic eubacterium. Thermotoga maritima reverse gyrase relaxes
      negatively supercoiled DNA in the presence of ADP or the non-hydrolyzable ATP
      analog ADPNP. Nucleotide binding is necessary, but not sufficient for the
      relaxation reaction. In the presence of ATP, positive supercoils are introduced
      at temperatures above 50 degrees C. However, ATP hydrolysis is stimulated by DNA
      already at 37 degrees C, suggesting that reverse gyrase is not frozen at this
      temperature, but capable of undergoing inter-domain communication. Positive
      supercoiling by reverse gyrase is strictly coupled to ATP hydrolysis. At the
      physiological temperature of 75 degrees C, reverse gyrase binds and hydrolyzes
      ATPgammaS. Surprisingly, ATPgammaS hydrolysis is stimulated by DNA, and
      efficiently promotes positive DNA supercoiling, demonstrating that inter-domain
      communication during positive supercoiling is fully functional with both ATP and
      ATPgammaS. These findings support a model for communication between helicase-like
      and topoisomerase domains in reverse gyrase, in which an ATP and DNA-induced
      closure of the cleft in the helicase-like domain initiates a cycle of
      conformational changes that leads to positive DNA supercoiling.

PMID- 17560603
TI  - Pathogenic and non-pathogenic polyglutamine tracts have similar structural
      properties: towards a length-dependent toxicity gradient.
AB  - Abnormally expanded polyglutamine (polyQ) tracts provide a gain of toxic
      functions to nine otherwise unrelated human proteins and induce progressive
      neurodegenerative diseases. Over the past ten years, it was suggested that only
      polyQ tracts longer than a specific threshold adopt a particular structure, which
      would be the cause of the apparent polyQ length-dependent toxicity threshold
      observed in polyQ diseases. We have used a combination of biochemical and
      biophysical approaches to compare the structural properties of polyQ of
      pathogenic and non-pathogenic lengths under various conditions. We observe that
      pathogenic and non-pathogenic polyQ, as soluble species and upon interaction with
      a partner, during aggregation, or as mature aggregates, display very similar
      structural properties. PolyQ length only influences the aggregation kinetics and,
      to a lesser extent, the stability of the aggregates. We thus propose that polyQ
      toxicity does not depend on a structural transition occurring above a specific
      threshold, but rather that polyQ tracts are inherently toxic sequences, whose
      deleterious effect gradually increases with their length. We discuss how polyQ
      properties and other cellular factors may explain the existence of an apparent
      polyQ length-dependent toxicity threshold.

PMID- 17560604
TI  - 19F-NMR reveals metal and operator-induced allostery in MerR.
AB  - Metalloregulators of the MerR family activate transcription upon metal binding by
      underwinding the operator-promoter DNA to permit open complex formation by pre
      bound RNA polymerase. Historically, MerR's allostery has been monitored only
      indirectly via nuclease sensitivity or by fluorescent nucleotide probes and was
      very specific for Hg(II), although purified MerR binds several thiophilic metals.
      To observe directly MerR's ligand-induced behavior we made 2-fluorotyrosine
      substituted MerR and found similar, minor changes in (19)F chemical shifts of
      tyrosine residues in the free protein exposed to Hg(II), Cd(II) or Zn(II).
      However, DNA binding elicits large chemical shift changes in MerR's tyrosine
      residues and in DNA-bound MerR Hg(II) provokes changes very distinct from those
      of Cd(II) or Zn(II). These chemical shift changes and other biophysical and
      phenotypic properties of wild-type MerR and relevant mutants reveal elements of
      an allosteric network that enables the coordination state of the metal binding
      site to direct metal-specific movements in the distant DNA binding site and the
      DNA-bound state also to affect the metal binding domain.

PMID- 17560605
TI  - A novel loop domain in superantigens extends their T cell receptor recognition
      site.
AB  - Superantigens (SAGs) interact with host immune receptors to induce a massive
      release of inflammatory cytokines that can lead to toxic shock syndrome and
      death. Bacterial SAGs can be classified into five distinct evolutionary groups.
      Group V SAGs are characterized by the alpha3-beta8 loop, a unique approximately
      15 amino acid residue extension that is required for optimal T cell activation.
      Here, we report the X-ray crystal structures of the group V SAG staphylococcal
      enterotoxin K (SEK) alone and in complex with the TCR hVbeta5.1 domain. SEK
      adopts a unique TCR binding orientation relative to other SAG-TCR complexes,
      which results in the alpha3-beta8 loop contacting the apical loop of framework
      region 4, thereby extending the known TCR recognition site of SAGs. These
      interactions are absolutely required for TCR binding and T cell activation by
      SEK, and dictate the TCR Vbeta domain specificity of SEK and other group V SAGs.

PMID- 17560606
TI  - Enzymatic and structural characterisation of amphinase, a novel cytotoxic
      ribonuclease from Rana pipiens oocytes.
AB  - Besides Onconase (ONC) and its V11/N20/R103-variant, oocytes of the Northern
      Leopard frog (Rana pipiens) contain another homologue of ribonuclease A, which we
      named Amphinase (Amph). Four variants (Amph-1-4) were isolated and sequenced,
      each 114 amino acid residues in length and N-glycosylated at two positions.
      Sequence identities (a) among the variants and (b) versus ONC are 86.8-99.1% and
      38.2-40.0%, respectively. When compared with other amphibian ribonucleases, a
      typical pattern of cysteine residues is evident but the N-terminal pyroglutamate
      residue is replaced by a six-residue extension. Amph variants have relatively
      weak ribonucleolytic activity that is insensitive to human ribonuclease inhibitor
      protein (RI). Values of k(cat)/K(M) with hypersensitive fluorogenic substrates
      are 10(4) and 10(2)-fold lower than the maximum values exhibited by ribonuclease
      A and ONC, respectively, and there is little cytosine/uracil or adenine/guanine
      discrimination at the B(1) or B(2) subsites, respectively. Amph variants have
      cytotoxic activity toward A-253 carcinoma cells that requires intact
      ribonucleolytic activity. The glycan component has little or no influence over
      single-stranded RNA cleavage, RI evasion or cytotoxicity. The crystal structures
      of natural and recombinant Amph-2 (determined at 1.8 and 1.9 A resolution,
      respectively) reveal that the N terminus is unlikely to play a catalytic role
      (but an unusual alpha2-beta1 loop may do so) and the B(2) subsite is rudimentary.
      At the active site, structural features that may contribute to the enzyme's low
      ribonucleolytic activity are the fixture of Lys14 in an obstructive position, the
      accompanying ejection of Lys42, and a lack of constraints on the conformations of
      Lys42 and His107.

PMID- 17560608
TI  - TGFBR2 gene expression and genetic association with schizophrenia.
AB  - TGFBR2 gene is a tumor suppressor gene located at chromosome 3p22, and the locus
      is reported to be linked with schizophrenia susceptibility. According to the
      previous studies, a reduced incidence of cancer is observed in schizophrenic
      patients compared with the general population and tumor suppressor genes may be
      associated with schizophrenia. We measured the mRNA expression of TGFBR2 gene in
      the peripheral leukocytes from 19 medication-free schizophrenics and 25
      medication-free major depressive patients compared with age- and sex-matched
      control subjects using a quantitative real-time PCR method. We also followed up
      the TGFBR2 mRNA expression levels from 13 schizophrenics after several weeks -
      antipsychotic treatments. The TGFBR2 mRNA levels of medication free
      schizophrenics were significantly higher than those of control subjects and
      decreased to almost the same level as controls after antipsychotic treatment. On
      the other hand, the TGFBR2 mRNA levels of medication-free major depressive
      patients were not significantly different from controls. In genetic studies, we
      failed to find any association between the TGFBR2 gene and schizophrenia with 10
      SNPs of TGFBR2 gene in Japanese subjects (279 subjects each) and there was no
      significant difference with haplotype analysis, either. Our results suggest that
      the TGFBR2 gene itself does not link to schizophrenia but that the TGFBR2 mRNA
      levels in the peripheral leukocytes may be a potential state marker for
      schizophrenia.

PMID- 17560607
TI  - The nucleoside triphosphate diphosphohydrolase-1/CD39 is incorporated into human
      immunodeficiency type 1 particles, where it remains biologically active.
AB  - Human immunodeficiency virus type 1 (HIV-1) carries a variety of host proteins in
      addition to virus-encoded structural proteins, both in its envelope and inside
      the viral particle. Previous studies have reported that the HIV-1 life-cycle is
      affected by such virus-associated host cell surface proteins. The nucleoside
      triphosphate diphosphohydrolase-1 (NTPDase1), also known as CD39, is a plasma
      membrane-bound ectoenzyme that hydrolyzes extracellular ATP and ADP to AMP. It
      has been shown that CD39 inhibits platelet function, and is thus a critical
      thromboregulatory molecule. We demonstrate here that host-derived CD39 is
      acquired by both laboratory-adapted and clinical variants of HIV-1 produced in
      cellular reservoirs of the virus. Moreover, purified CD39-bearing virions, but
      not isogenic viruses lacking CD39, display strong ATPase and ADPase activities.
      It is of particular interest that virions bearing this cellular enzyme can
      inhibit ADP-induced platelet aggregation, an effect blocked by an NTPDase
      inhibitor. On the basis of published and the present data on the functionality of
      human cellular proteins embedded within HIV-1, it can be proposed that these
      proteins might contribute to some of the immunologic deficiencies seen in
      infected individuals.

PMID- 17560609
TI  - Hemorrhagic shock in the rat: comparison of carotid and femoral cannulation.
AB  - BACKGROUND: The reservoir model of rat hemorrhagic shock is widely used. In this
      model, either the carotid or femoral artery can be cannulated to withdraw blood
      and measure pressure. In animals undergoing hemorrhage using the carotid
      approach, we observed seizure activity during the post-shock period, suggesting
      some degree of brain damage. The hypothesis of the present study is that survival
      in a model of severe hemorrhagic shock would be higher with femoral cannulation
      than with carotid cannulation. MATERIALS AND METHODS: All animals (n = 90) were
      anesthetized with isoflurane using an anesthesia vaporizer while breathing
      spontaneously. In group 1, the left carotid artery and jugular vein were
      cannulated; in group 2, the left femoral artery and vein were cannulated.
      Following a period of hemorrhagic shock (20 to 30 mmHg for 30, 60, or 50-90 min),
      resuscitation was performed through the venous cannula by giving L-lactated
      Ringer's (21 mL/kg) and returning the shed blood. RESULTS: In the carotid
      cannulation group, nearly 50% of the animals had seizures after resuscitation,
      and most of those animals died following the seizures. The 24-h survival rate in
      the femoral artery cannulation group was significantly higher than in the carotid
      artery cannulation group. Femoral cannulated animals had no seizures following
      reperfusion. CONCLUSIONS: Femoral artery cannulation was associated with
      considerably better survival than carotid artery cannulation in this rodent model
      of hemorrhagic shock. The occurrence of seizures in animals undergoing carotid
      cannulation suggests brain damage from inadequate cerebral perfusion or
      subsequent reperfusion damage.

PMID- 17560610
TI  - Reduction of post-surgical adhesion formation with tranilast.
AB  - BACKGROUND: Preclinical studies using the rabbit sidewall and double uterine horn
      models were used to assess time and dose response of tranilast delivered via
      subcutaneous pump, p.o., or as an intraperitoneal bolus in viscoelastic gels as
      well as an intraperitoneal biodegradable poly(p-dioxanone) fiber in reducing
      adhesions compared to vehicle controls. MATERIALS AND METHODS: New Zealand white
      rabbits underwent laparotomy followed by: 1) uterine horn abrasion and peripheral
      devascularization or 2) cecal abrasion and sidewall deperitonealization.
      Tranilast treatment using various vehicles and dosages was compared to vehicle
      alone versus no treatment. Animals were euthanized after 7 to 21 days. Adhesion
      formation was assessed by two independent observers. RESULTS: There were
      reductions in adhesion formation when drug was delivered topically, but oral drug
      alone was not effective. When tranilast was given preoperatively, oral drug added
      to the adhesion reduction of intraperitoneal administered drug. Tranilast in a
      viscoelastic carrier as well as in a biodegradable fiber was effective at
      reducing adhesions in the double uterine horn model. The slow release of
      tranilast from a biodegradable rod produced overall the best results. There were
      no safety issues. CONCLUSION: Tranilast was effective in reducing adhesions when
      given in a variety of vehicles in different rabbit models of adhesion formation.
      Overall, the sustained intraperitoneal delivery of tranilast from biodegradable
      fibers was the most suitable for clinical testing.

PMID- 17560611
TI  - Bone marrow transplantation: does it stop MS progression?
AB  - Based upon the theory that MS is an acquired autoimmune disease and not purely
      genetically defined, complete ablation of the defective immune system and
      replacement with a naive non-disease-causing system de novo from stem cells
      autologously-obtained should lead to a long-lasting remission of disease. The
      rationale and methodology are discussed along with recommendations for patient
      selection. Results of several small studies are presented along with some
      preliminary results from the ongoing Canadian effort.

PMID- 17560612
TI  - Expanding autologous multipotent mesenchymal bone marrow stromal cells.
AB  - In this brief review, I will start by redefining the cells: mesenchymal stem
      cells should now be called multipotent mesenchymal stromal cells, with the same
      acronym (MSC). I will review the role of MSC as immunosuppressive and
      immunoprotected cells, and then go on to describe how cell culture strategies may
      depend on the desired functionality of MSC. In order to expand MSC in vitro, the
      cells have to be cultured as adherent cells on plastic surfaces. To obtain the
      best cell culture conditions, a number of methodological decisions have to be
      made. Special considerations are necessary if the cells are to be used for the
      treatment of patients.

PMID- 17560613
TI  - Olmesartan blocks advanced glycation end products (AGEs)-induced angiogenesis in
      vitro by suppressing receptor for AGEs (RAGE) expression.
AB  - We have previously shown that advanced glycation end products (AGEs)-their
      receptor (RAGE) interaction elicits angiogenesis through autocrine production of
      vascular endothelial growth factor (VEGF), thus suggesting the active involvement
      of the AGEs-RAGE system in proliferative diabetic retinopathy (PDR). Since the
      crosstalk between the AGEs-RAGE and the renin-angiotensin system has also been
      proposed in the pathogenesis of PDR, we investigated here whether olmesartan, an
      angiotensin II type 1 receptor blocker, inhibited the AGEs-elicited angiogenesis
      in vitro by suppressing the NF-kappaB-mediated RAGE expression. Olmesartan
      significantly inhibited the AGEs-induced NF-kappaB promoter activity and RAGE
      gene expression in cultured microvascular endothelial cells (ECs). Further,
      olmesartan was found to block the AGEs-induced up-regulation of VEGF mRNA levels
      and consequent increase in DNA synthesis in ECs. These results demonstrated for
      the first time that olmesartan inhibited the AGEs signaling to angiogenesis by
      suppressing RAGE expression in ECs. Our present study suggests that blockade of
      the renin-angiotensin system by olmesartan may play a protective role against PDR
      by attenuating the deleterious effects of AGEs via down-regulation of RAGE.

PMID- 17560614
TI  - Computerized morphometric analysis of microvasculature in non-small cell lung
      carcinoma.
AB  - Interactions between tumor cells and microvasculature are particularly critical.
      This computerized morphometric study was designed to analyze the distance between
      cancer cells and blood vessels and microvasculature organization in non-small
      cell lung carcinoma (NSCLC) comparing squamous cell carcinoma (SCC) and
      adenocarcinoma (ADC). Seventy nine nests of tumor cells, located less than or
      more than 3 mm from the invading edge, with a similar surface area, and their
      surrounding stroma were analyzed. After immunolabeling with an antihuman CD34
      monoclonal antibody, computerized morphometric analyses of microvascular density
      (MVD), distribution of microvessels within stroma, and fractions of carcinomatous
      cells over various distances from microvessels were performed. This analysis
      showed a significantly higher MVD score in ADC than in SCC, particularly close to
      the invading edge (382+/-57 in ADC <3 mm; 242+/-28 in SCC <3 mm, p=0.015).
      Moreover, a significantly higher proportion of cancer cells was situated more
      than 75 microm from microvessels in SCC than in ADC, regardless of their site in
      relation to the invading edge (for example, 25+/-5% in ADC <3 mm; 52+/-3% in SCC
      <3 mm, p=0.001).

PMID- 17560615
TI  - Tumor microvasculature and microenvironment: targets for anti-angiogenesis and
      normalization.
AB  - A solid tumor forms an organ-like entity comprised of neoplastic cells and non
      transformed host stromal cells embedded in an extracellular matrix. Similar to
      normal tissues, blood vessels nourish cells residing in tumors. However, unlike
      normal blood vessels, tumor vasculature has abnormal organization, structure, and
      function. Tumor vessels are leaky and blood flow is heterogeneous and often
      compromised. Vascular hyperpermeability and the lack of functional lymphatic
      vessels inside tumors cause elevation of interstitial fluid pressure in solid
      tumors. Each of these abnormalities forms a physiological barrier to the delivery
      of therapeutic agents to tumors. Furthermore, elevated tumor interstitial fluid
      pressure increases fluid flow from the tumor margin into the peri-tumor area and
      may facilitate peri-tumor lymphatic hyperplasia and metastasis. Abnormal
      microcirculation in tumors also leads to a hostile microenvironment characterized
      by hypoxia and acidosis, which hinder the effectiveness of anti-tumor treatments
      such as radiation therapy and chemotherapy. In addition, host-tumor interactions
      regulate expression of pro- and anti-angiogenic factors and hence contribute to
      their imbalance and resulting pathophysiological characteristics of the tumor.
      Restoration of pro- and anti-angiogenic balance in tumors may "normalize" tumor
      vasculature and thus improve its function. Indeed, anti-angiogenic treatments
      directly targeting angiogenic signaling pathways as well as indirectly modulating
      angiogenesis show normalization of tumor vasculature and microenvironment at
      least transiently in both preclinical and clinical settings. Combination of
      cytotoxic therapy and anti-angiogenic treatment during the vascular normalization
      exhibits synergistic effect.

PMID- 17560616
TI  - Elevated sodium chloride concentrations enhance the bystander effects induced by
      low dose alpha-particle irradiation.
AB  - Previous studies have shown that high NaCl can be genotoxic, either alone or
      combined with irradiation. However, little is known about the relationship
      between environmental NaCl at elevated conditions and radiation-induced bystander
      effects (RIBE). RIBE, which has been considered as non-targeted bystander
      responses, has been demonstrated to occur widely in various cell lines. In the
      present study, RIBE under the elevated NaCl culture condition was assessed in AG
      1522 cells by both the induction of gamma-H2AX, a reliable marker of DNA double
      strand break (DSB) for the early process (<1h post irradiation), and the
      generation of micronuclei (MN), a sensitive marker for relative long process of
      RIBE. Our results showed that in the absence of irradiation, NaCl at elevated
      concentration such as 8.0, 9.0 and 10.0g/L did not significantly increase the
      frequency of gamma-H2AX foci-positive cells and the number of foci per positive
      cell comparing with that NaCl at a normal concentration (6.8g/L). However, with
      0.2cGy alpha-particle irradiation, the induced fraction of gamma-H2AX foci
      positive cells and the number of induced gamma-H2AX foci per positive cell were
      significantly increased in both irradiated and adjacent non-irradiated regions.
      Similarly, the induction of MN by 0.2cGy alpha-particle irradiation also
      increased with the elevated NaCl concentrations. With N(G)-methyl-l-arginine, an
      inhibitor of nitric oxide synthase, the induced fraction of foci-positive cells
      was effectively inhibited both in 0.2cGy alpha-particle irradiated and adjacent
      non-irradiated regions under either normal or elevated NaCl conditions. These
      results suggested that the cultures with elevated NaCl medium magnified the
      damage effects induced by the low dose alpha-particle irradiation and nitric
      oxide generated by irradiation was also very important in this process.

PMID- 17560617
TI  - An improvement in perception of self-generated tactile stimuli following theta
      burst stimulation of primary motor cortex.
AB  - Recent studies have shown that self-generated tactile sensations are perceived as
      weaker than the same sensations externally generated. This has been linked to a
      central comparator mechanism that uses efference copy to attenuate the
      predictable component of sensory inputs arising from one's own actions in order
      to enhance the salience of external stimuli. To provide a quantitative measure of
      this attenuation, a force-matching task was developed in which subjects
      experience a force applied to their finger and are then required to match the
      perceived force by actively pushing on the finger using their other hand. The
      attenuation of predictable sensory input results in subjects producing a larger
      active force than was experienced passively. Here, we have examined the effects
      of a novel rTMS protocol, theta-burst stimulation (TBS), over primary motor
      cortex on this attenuation. TBS can alter the excitability of motor cortex to
      incoming activity. We show that application of a 20s continuous train of TBS,
      that depresses motor cortex, significantly improves performance in a force
      matching task. This suggests that the TBS intervention disturbed the predictive
      process that uses efference copy signals to attenuate predictable sensory input.
      A possible explanation for the effect is that TBS has a differential effect on
      the populations of neurones that generate motor output in M1 than on those neural
      structures that are involved in generating an efference copy of the motor
      command.

PMID- 17560618
TI  - Evidence for hypothalamic dysregulation in mouse models of anorexia as well as in
      humans.
AB  - Eating disorders constitute major medical health problems in the western world.
      Even though little is known about the molecular mechanisms behind abnormal eating
      behavior, it has become clear that the central nervous system (CNS), particularly
      the hypothalamus, plays a significant role. The anorexic anx/anx mouse is a
      unique model for studying food intake and energy expenditure. The anx mutation is
      linked to marked alterations in hypothalamic distributions of signal substances
      known to have potent regulatory roles in the control of food intake. Another
      mouse model that displays an anorectic phenotype similar to the anx/anx mouse is
      the Contactin KO mouse. This model displays very similar hypothalamic alterations
      as seen in the anx/anx mouse, arguing for a role of these specific hypothalamic
      changes in an anorectic phenotype. In human eating disorders, hypothalamic
      systems corresponding to those defective in mouse models could be compromised
      since autoantibodies against melanocortin peptides have been detected in
      anorectic and bulimic patients. These findings represent research avenues that
      may lead to a better understanding of eating disorders and development of
      targeted therapeutic approaches.

PMID- 17560620
TI  - Establishment and characterization of human pancreatic adenocarcinoma cell line
      in tissue culture and the nude mouse.
AB  - We established a human pancreatic carcinoma cell line, designated SPH, from
      cancerous ascites of a 57-year-old male patient with ductal adenocarcinoma of the
      pancreas. The cells have been cultured for 32 months with RPMI-1640 medium
      supplemental with 10% fetal calf serum. The population doubling time of this cell
      line was about 35 h, and the modal number of chromosomes was 85 at passage 20.
      The cells produced CA19-9, SPan-1, and DUPAN-2 in the conditioned medium and
      formed tumors in nude mice, the histology of which was similar to that of the
      primary tumor. Based on these findings, this cell line is considered to be a very
      useful model for studying many aspects of primary and metastatic pancreatic
      cancer cell biology.

PMID- 17560621
TI  - Isolation and characterization of monoclonal antibodies elicited by trimeric HIV
      1 Env gp140 protein immunogens.
AB  - Eleven anti-HIV Env monoclonal antibodies (MAbs) were isolated from mice
      immunized with soluble Env proteins derived from the clade B Env, SF162, or
      DeltaV2 (a derivative of SF162 lacking the V2 loop). All six anti-gp120 MAbs
      studied, neutralized SF162 and their activities were dependent by the
      glycosylation patterns of the V1, V2 or V3 loops. Only one anti-gp120 MAb (an
      anti-V3 MAb) displayed cross-neutralizing activity, which was influenced by the
      type of V1 loop present on the target heterologous viruses. None of the five anti
      gp41 MAbs studied displayed anti-SF162 neutralizing activity. Our studies
      indicate that the current limitation of soluble HIV Env gp140 immunogens to
      elicit robust cross-reactive neutralizing antibody responses is not only due to
      the elicitation of high titers of homologous antibodies but also due to the
      elicitation of antibodies whose epitopes are naturally occluded, or not present,
      on the virion-associated Env.

PMID- 17560622
TI  - Differential amplification of adenovirus vectors by flanking the packaging signal
      with attB/attP-PhiC31 sequences: implications for helper-dependent adenovirus
      production.
AB  - Current strategies to amplify helper-dependent adenovirus, based on excision of
      the packaging signal, do not routinely reduce helper adenovirus contamination
      below 1%. Here, we have tested if reducing the efficiency of the packaging
      process of the helper adenovirus could impair its packaging without affecting
      helper-dependent adenovirus production. Interestingly, insertion of attB/attP
      PhiC31 sequences flanking the packaging signal significantly lengthens adenovirus
      cycle up to 60 h without reducing virus viability or production yield. This delay
      occurs in the absence of PhiC31 recombinase indicating that other mechanisms
      different from excision of packaging signal must be involved. In addition, at 36
      h post-coinfection helper-dependent adenovirus are efficiently produced, while
      production levels of helper attB/attP-modified adenovirus are 100-1000 times
      lower than controls. Therefore, these results suggest that attB/attP-mediated
      packaging impairment of the adenovirus genome is an attractive strategy to
      significantly reduce helper adenovirus contamination in helper-dependent
      adenovirus preparations, which in turn would facilitate scaling-up processes for
      clinical grade preparations.

PMID- 17560623
TI  - Monitoring source water for microbial contamination: evaluation of water quality
      measures.
AB  - Watershed management programs often rely on monitoring for a large number of
      water quality parameters to define contaminant issues. While coliforms have
      traditionally been used to identify microbial contamination, these indicators
      cannot discriminate among potential contaminant sources. Microbial source
      tracking (MST) can provide the missing link that implicates the sources of
      contamination. The objective of this study was to use a weight-of-evidence
      approach (land use analysis using GIS, sanitary surveys, traditional water
      quality monitoring, and MST targets) to identify sources of pollution within a
      watershed that contains a raw drinking water source. For the study watersheds,
      statistical analyses demonstrated that one measure each of particulate matter
      (turbidity, particle counts), organic matter (total organic carbon, dissolved
      organic carbon, UV(254) absorbance), and indicator organisms (fecal coliforms,
      enterococci) were adequate for characterizing water quality. While these
      traditional parameters were useful for assessing overall water quality, they were
      not intended to differentiate between microbial sources at different locations.
      In contrast, the MST targets utilized (Rhodococcus coprophilus, sorbitol
      fermenting Bifidobacteria, and male-specific coliphages) pinpointed specific
      sources of microbial pollution. However, these targets could not be used for
      routine monitoring due to a high percentage of non-detects.

PMID- 17560624
TI  - Characterisation of colloidal and particulate organic carbon in freshwaters by
      thermal fluorescence quenching.
AB  - Three-dimensional excitation-emission matrix (EEM) fluorescence with thermal
      quenching has been applied to raw and size-fractionated freshwaters. To size
      fractionate organic matter, sequential filtration through mixed-ester-cellulose
      membrane filters with nominal pore size of 1.2, 0.1 and 0.025 microm were used.
      Humic-like fluorophores (peaks A and C) have been found to dominate EEMs of raw
      and all size fractions of studied waters. Peak A fluorescence intensity has been
      found to be more thermally sensitive than peak C fluorescence intensity. Humic
      like fluorescence intensity was generally size independent, which indicated that
      it was present mainly in the smallest size fraction (<0.025 microm). This was
      confirmed by total organic carbon (TOC) measurements. Peak T (tryptophan-like)
      fluorescence, that is widely associated with biological activity, exhibited a
      greater thermal sensitivity of fluorescence intensity in the larger size
      fractions, demonstrating the presence of more than one fluorophore in different
      size fractions at this location in optical space. Thermal fluorescence quenching
      provides insights into organic matter variability and associated colloidal
      characteristics.

PMID- 17560625
TI  - Exposure to sublethal concentrations of Zn(II) and Cu(II) changes biochemical
      parameters in Leporinus obtusidens.
AB  - The aim of the present study was to assess the effect of the exposure of
      Leporinus obtusidens (Piava) to zinc and copper on catalase activity in the
      liver, delta-aminolevulinate dehidratase (delta-ALA-D) activity in liver, muscle,
      brain and kidney, and thiobarbituric reactive species (TBARS) in brain, muscle
      and liver. In addition, hematological parameters were measured in blood. The fish
      were exposed to 10% and 20% of the derived LC(50) values, 2.3 and 4.6 mg Zn l(-1)
      and 0.02 and 0.04 mg Cu l(-1), and sampled on days 30 and 45. Exposure to Zn(II)
      and Cu(II) decreased hematological parameters and also delta-ALA-D activity
      mainly in liver and kidney at all concentrations tested. Liver catalase activity
      increased after zinc or copper exposure at all concentrations and exposure times
      tested. Thiobarbituric reactive substances (TBARS) increased in the brain and
      liver of the fish exposed to zinc(II) for 45 days at both metal concentrations.
      In muscle, zinc(II) increased TBARS production at both exposure times and
      concentrations tested. Copper(II) exposure reduced the TBARS levels in liver at
      both concentrations and times tested. In brain, there was a decrease in TBARS
      levels only after 45 days of exposure. In muscle, this decrease was observed
      after 30 days of exposure at both concentrations. Although zinc and copper are
      required as microelements in the cells, our results showed that the sublethal
      concentrations of these metals can change biochemical parameters which may alter
      normal cellular function. These results pointed out the differential sensitivity
      of fish tissues to essential, but also toxic and environmentally relevant metals.
      The alterations of distinct biochemical parameters in fish tissues certainly
      contribute to the toxicity of Zn and Cu, and are of importance for an area that
      has been growing and has still been poorly explored in the literature.

PMID- 17560626
TI  - Background levels and dietary intake of PCDD/Fs in domestic and imported meat in
      South Korea.
AB  - A survey was conducted in South Korea to determine residual levels and dietary
      intake of polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs)
      from meat. Altogether 119 domestic and 164 imported samples of beef, pork, and
      chicken were examined. The mean levels of PCDD/Fs in upper bound were 0.21, 0.22,
      and 0.04pg WHO-TEQ/g fat for beef, pork, and chicken, respectively. The low level
      of PCDD/Fs in chicken probably resulted from the low fat content in the samples
      used. The samples were separated into domestic and imported products in order to
      investigate the sources of contamination. PCDFs were the more dominant congeners
      in domestic beef and were similar to those found from emission of incineration.
      However, the congener profiles of domestic beef and incineration were difficult
      to compare because the environmental fate and animal metabolism were involved.
      The upper bound dietary intake of PCDD/Fs from beef, pork and chicken was
      calculated to be 0.04pg/WHO-TEQ/kgbw/day. The combined consumption of beef, pork,
      and chicken was found to be 84.8g per day for a person weighing 60kg and
      represented 5.7% of their total daily food intake.

PMID- 17560627
TI  - Role of dissolved organic carbon in the cosorption of copper and phthalate esters
      onto Yellow River sediments.
AB  - Although the sorption mechanism of hydrophobic organic pollutants on soils or
      sediments has been widely studied, the effects of coexisting heavy metals are
      seldom reported, especially the role of dissolved organic carbon (DOC) in
      sorption interactions involving heavy metals. This paper investigates the
      sorption interactions of phthalate esters (diethyl phthalate, DEP, and di-n-butyl
      phthalate, DnBP) and copper on Yellow River sediment in the presence of DOC. The
      results indicate that the sorption hardly varies for DEP but increases up to 20%
      for DnBP as the copper concentration increases in a water-sediment system with
      extremely low concentration of DOC. The copper-induced sorption of DnBP could be
      due to its complexation with copper, as well as its hydrophobicity. In a water
      sediment system with the addition of 6.34 mg l(-1) of commercial humic acid (HA),
      the sorption of DEP is decreased by up to 37%, and that of DnBP is enhanced by up
      to 41%, as copper is gradually added. This finding is also consistent with the
      results for a river water-sediment system containing 8.1 mg l(-1) natural DOC.
      The copper-influenced sorption of DEP and DnBP are found to be due to the binding
      of copper to DOC that leads to the configuration change of DOC and thus to its
      enhanced sorption to sediment. By using polarograph and fluorescence spectrograph
      techniques, the complexation competition among coexisting phthalates, copper and
      DOC is examined. The resulting data confirm the significant role of DOC in
      sorption interactions.

PMID- 17560628
TI  - Accumulation and partitioning of heavy metals in mangroves: a synthesis of field
      based studies.
AB  - We report the findings of a comparative analysis examining patterns of
      accumulation and partitioning of the heavy metals copper (Cu), lead (Pb) and zinc
      (Zn) in mangroves from available field-based studies to date, employing both
      species level analyses and a phylogenetic approach. Despite mangroves being a
      taxonomically diverse group, metal accumulation and partitioning for all metals
      examined were broadly similar across genera and families. Patterns of metal
      accumulation were also similar regardless of whether species were classified as
      salt secreting or non-secreting. Metals were accumulated in roots to
      concentrations similar to those of adjacent sediments with root bio-concentration
      factors (BCF; ratio of root metal to sediment metal concentration) of 1< or =.
      Root BCFs were constant across the exposure range for all metals. Metal
      concentrations in leaves were half that of roots or lower. Essential metals (Cu
      and Zn; translocation factors (TF; ratio of leaf metal to root metal
      concentration) of 0.52 and 0.53, and leaf BCFs of 0.47 and 0.51, respectively)
      showed greater mobility than non-essential metals (Pb; TF of 0.31 and leaf BCF of
      0.11). Leaf BCFs for the essential metals Cu and Zn decreased as environmental
      concentrations increased. The non-essential metal Pb was excluded from leaf
      tissue regardless of environmental concentrations. Thus mangroves as a group tend
      to operate as excluder species for non-essential metals and regulators of
      essential metals. For phytoremediation initiatives, mangrove ecosystems are
      perhaps best employed as phytostabilisers, potentially aiding in the retention of
      toxic metals and thereby reducing transport to adjacent estuarine and marine
      systems.

PMID- 17560629
TI  - Bone marrow trephines containing lymphoid aggregates from patients with
      rheumatoid and other autoimmune disorders frequently show clonal B-cell
      infiltrates.
AB  - In bone marrow trephines, morphological and immunohistochemical criteria may not
      be sufficient to discriminate reactive from malignant lymphoid infiltrates. The
      aim of this study was to determine whether the detection of clonal immunoglobulin
      heavy chain (IGH) gene rearrangements is a reliable and specific marker for
      malignant B-cell clones in bone marrow biopsies. Bone marrow trephines with
      infiltration by different types of low-grade B-cell non-Hodgkin lymphoma (n =
      32), reactive lymphoid hyperplasia (n = 18), and reactive lymphoid aggregates (n
      = 15), including 5 patients with rheumatoid or other autoimmune disorders, were
      analyzed by morphology, immunohistochemistry, IGH gene rearrangement (polymerase
      chain reaction), and DNA sequence analysis in selected cases. In 22 (68.8%) of 32
      patients with B-cell non-Hodgkin lymphoma, a clonal IGH gene rearrangement was
      detected. Of the reactive cases, 1 of 18 patients with lymphoid hyperplasia
      demonstrated clonality, and 9 (60%) of 15 patients with reactive lymphoid
      aggregates gave a clonal result (GeneScan analysis). DNA sequence analysis was
      performed in 7 of the latter patients confirming clonality in 6. Four of the
      patients with B-cell clonality had an autoimmune disorder. None of these patients
      developed a malignant lymphoma during follow-up. Thus, the molecular detection of
      a clonal rearrangement of the IGH gene may support the diagnosis of a malignant
      lymphoma infiltrating the bone marrow. However, morphologically and
      immunohistochemically benign lymphoid aggregates might also harbor B-cell clones
      especially in patients with autoimmune disorders. Therefore, the detection of
      clonality has to be interpreted with utmost care and does not qualify for the
      unequivocal diagnosis of a malignant B-cell lymphoma.

PMID- 17560630
TI  - Temporal trends (1987-2002) of persistent, bioaccumulative and toxic (PBT)
      chemicals in beluga whales (Delphinapterus leucas) from the St. Lawrence Estuary,
      Canada.
AB  - Temporal trends of persistent, bioaccumulative and toxic (PBT) chemicals were
      examined in beluga whales (Delphinapterus leucas) from the St. Lawrence Estuary
      (SLE), Canada. Blubber samples of 86 adult belugas were collected from animals
      stranded on the shore of the SLE between 1987 and 2002 and analyzed for several
      regulated PBTs, including polychlorinated biphenyls (PCBs),
      p,p'dichlorodiphenyltrichloroethane (DDT) and its metabolites, chlordane (CHL)
      and related compounds, hexachlorocyclohexane (HCH) isomers, hexachlorobenzene
      (HCB) and Mirex. In addition, time trends of tris(4-chlorophenyl)methane (TCPMe)
      and tris(4-chlorophenyl)methanol (TCPMOH), two compounds that may origin from DDT
      formulations, were also examined. Concentrations of most of the PBTs examined had
      exponentially decreased by at least a factor of two (half-life time (t(1/2))<15
      years) in beluga between 1987 and 2002 while no increasing trends were observed
      for any of the PBTs measured. The decreasing trends of PBT concentrations in SLE
      beluga may be due to a decline in contamination of its diet following North
      American and international regulations on the use and production of these
      compounds or by a change in its diet itself or by a combination of both. Some
      PBTs did not exhibit any significant trends in beluga possibly because the most
      intense elimination phase subsequent to legislative regulations occurred prior to
      the 1987-2002 time period. Other chemicals, such gamma-HCH, did not significantly
      decrease likely because they are still currently used in some restricted
      applications. Conversely, alpha-HCH showed a significant decreasing trend
      indicating that SigmaHCHs is not representative of all HCHs. Both TCPMe and
      TCPMOH exhibited no trends in beluga during the time period examined. The
      metabolic capacity of SLE beluga has apparently accelerated the depletion of at
      least one PBT, namely CB-28/31. A significant relationship between the half-life
      of PBTs in beluga and log Kow was observed for most of the chemicals examined.
      Several factors are expected to have influenced the temporal changes of PBT
      concentrations in beluga which limit the usefulness of this species as a
      bioindicator of changes in PBT contamination in the SLE ecosystem.

PMID- 17560631
TI  - Differentiation of market coffee and its infusions in view of their mineral
      composition.
AB  - The concentrations of 14 elements (Ca, Mg, K, Na, P, Co, Mn, Fe, Cr, Ni, Zn, Cu,
      Cd, Pb) were determined in market coffee samples after dry mineralisation of both
      dry samples and infusions evaporated to dryness. The total metal contents were
      analysed by flame atomic absorption spectrometry (F-AAS) using deuterium
      background correction. Phosphorus was determined in the form of phosphomolybdate
      by spectrophotometric method. Reliability of the procedure was checked by the
      analysis of the certified reference materials Tea (NCS DC 73351), Cabbage (IAEA
      359) and Spinach leaves (NIST-1570). It was concluded, based on RDA calculated
      for essential metals, that coffee infusions are not an important source of
      bioelements in human diet. In the case of toxic elements Provisional Tolerable
      Weekly Intake (PTWI) was estimated and there is no health hazard associated with
      exposure to Cd and Pb via coffee consumption. Significant correlation
      coefficients (p<0.001, p<0.01 and p<0.05) were found between concentrations of
      some metals in coffee. Factor analysis and canonical analysis were applied to the
      data processing in order to characterise the market coffee samples. The 12 metals
      determined were considered as chemical descriptors of each sample. Based on the
      mineral composition, it was possible to differentiate chemometrically particular
      types of coffee distinguishing arabica from robusta, ground from instant coffee,
      and their infusions.

PMID- 17560632
TI  - Polybrominated diphenyl ethers in fish and sediment from river polluted by
      electronic waste.
AB  - The present study investigated contamination of polybrominated diphenyl ethers
      (PBDEs) in sediment and fish samples collected from rivers in Guiyu, China where
      electronic waste (e-waste) is recycled and disposed. PBDE congeners with mono-to
      hepta-brominated and deca-brominated substitutions were detected using (13)C(12)
      isotope dilution GC/MS/MS and GC/MS methods, respectively. The total PBDE
      concentrations ranged from 4434 to 16088 ng/g (dry weight) in Nanyang River bank
      sediment, from 55 to 445 ng/g in Nanyang River bottom sediment and 51.3 to 365
      ng/g in Lianjiang River bottom sediment in Guiyu compared with those from 16.1 to
      21.4 ng/g in wastewater discharged from a vehicle repairing workshop in Lo Uk
      Tsuen in Hong Kong. No PBDE congeners were detected in bottom sediment and fish
      from Mai Po Marshes in Hong Kong. The mean concentrations of total PBDEs in mixed
      muscles of tilapia (Oreochromis spp) from Lianjiang River were 115 ng/g wet
      weight (ww) and from wastewater in Hong Kong were 4.1 ng/g ww. Highest mean PBDE
      concentration was obtained in liver (2687 ng/g ww), followed by abdomen muscle
      (1088 ng/g ww) of bighead carp (Aristichthys nobilis) collected from Nanyang
      River. A significant correlation of concentration of each PBDE congener between
      sediment and muscle from Guiyu was observed. The present results of total PBDEs
      in sediment and fish were 10 and 1000 times higher than other studies. Open
      burning and dumping of e-waste are the major causes of PBDE contamination.

PMID- 17560633
TI  - The endogenous thrombin potential and the risk of venous thromboembolism.
AB  - BACKGROUND: The risk of venous thromboembolism (VTE) is increased by an excess of
      procoagulant or by a defect of anticoagulant proteins, with circumstantial risk
      factors playing a significant contribution. These conditions are directly linked
      to or are compatible with increased thrombin generation. Assuming that the more
      thrombin is generated the higher is the risk of VTE, an overall coagulation test
      monitoring ex vivo thrombin generation and reflecting the interaction of pro- and
      anticoagulant proteins would be useful to determine the risk of VTE. PATIENTS AND
      METHODS: This hypothesis was tested by measuring the endogenous thrombin
      potential (ETP) without or with thrombomodulin (TM) in plasmas from 403
      individuals stratified according to their relative risk of VTE (no, low,
      intermediate, or high risk) according to whether or not they had congenital
      and/or circumstantial risk factors. Odds ratio (OR) and 95% confidence interval
      (CI), taken as a measure of the relative risk of having high levels of ETP, were
      calculated for the different categories relatively to the no-risk category.
      RESULTS: When the ETP was measured with TM, ORs (95% CI) were 2.10 (1.23-3.60);
      4.03 (2.18-7.45) and 4.96 (2.40-10.23) for the low-, intermediate and high-risk
      category. When ETP was measured without TM there was no gradient of OR values as
      function of the risk category. CONCLUSIONS: ETP measured with TM may help to
      distinguish individuals with different risk of VTE, however, the practical
      utility of measuring ETP in clinical practice remains to be evaluated in
      prospective studies.

PMID- 17560634
TI  - The role of angiogenesis and COX-2 expression in the evolution of vulvar lichen
      sclerosus to squamous cell carcinoma of the vulva.
AB  - OBJECTIVES: We aimed to determine whether premalignant changes in vulvar lichen
      sclerosus (LS) could be identified by analysing markers of angiogenesis and the
      expression of the enzyme cyclooxygenase-2 (COX-2). METHODS: Eight cases of
      histologically diagnosed vulvar LS, which showed an evolution to carcinoma of the
      vulva histologically documented, were compared to 10 cases of vulvar LS, for
      which follow-up information was available for at least 9 years, and to 10 cases
      of LS adjacent to squamous cell carcinoma (SCC) of the vulva. The microvessel
      density (MVD), and the expression of vascular endothelial growth factor (VEGF)
      and of COX-2 were analysed. RESULTS: Difference of MVD between unchanged LS cases
      and LS cases evolving to SCC and LS adjacent to SCC cases was statistically
      significant (P=0.008, Wilcoxon Mann-Whitney test). Difference of VEGF and COX-2
      expression between unchanged LS cases and LS cases evolving to SCC and LS
      adjacent to SCC cases were statistically significant (P=0.007 and P=0.01,
      respectively; Fisher's exact test). CONCLUSIONS: Our study addresses the
      possibility that immunohistochemical studies may add information to permit the
      identification of LS as a precursor lesion that has a greater potential to evolve
      into SCC. These data may identify characteristics of vulvar LS disclosing
      alterations that indicate the further development to cancer; therefore, it may
      allow the identification of a group of LS patients who need a careful follow-up
      and adjunctive biopsies.

PMID- 17560635
TI  - Laparoscopic sentinel lymph node mapping for cervix cancer--a detailed evaluation
      and time analysis.
AB  - OBJECTIVE: To provide data from a US center on laparoscopic (LSC) approach to
      sentinel lymph node (SLN) detection in cervix cancer with detailed time analysis.
      METHODS: This prospective trial enrolled patients with stage IA2-IIA cervix
      cancer undergoing primary radical surgery. Tc-99 radiocolloid was injected the
      morning of surgery, followed by hybrid SPECT/CT lymphoscintigraphy. Blue dye
      injection occurred just prior to incision. After bilateral LSC SLN detection, all
      patients received complete LSC pelvic lymphadenectomy. Institutional SLN protocol
      was followed for frozen section, hematoxylin and eosin, and cytokeratin staining.
      RESULTS: Between December 2003 and February 2006, 20 enrolled patients received 9
      LSC-assisted radical vaginal hysterectomies, 7 radical abdominal hysterectomies,
      2 LSC-assisted radical vaginal trachelectomies, and 2 LSC lymphadenectomies alone
      (secondary to positive lymph nodes). Mean tumor size was 2.5 cm. Nineteen percent
      of the 64 SLNs were found in unusual sites, including common iliac (11%),
      presacral (5%) and para-aortic (3%). The negative predictive value was 100%. The
      combined technique detected SLNs bilaterally in all patients. If blue dye alone
      was used, this rate would have dropped to 67.5% and was negatively correlated
      with elapsed surgical time (-0.7; p=0.002). The ability to visualize blue SLNs
      remained steady for 30 min and was completely gone by 50 min. CONCLUSIONS:
      Laparoscopic SLN mapping can be newly introduced into gynecologic oncology
      centers with high detection rates and negative predictive values. The
      visualization of blue dye in SLNs is transient, and this negative time
      correlation may explain the previously reported inferior detection rates with
      this technique. CLINICAL TRIAL REGISTRATION.: ClinicalTrials.gov,
      http://www.clinicaltrials.gov, NCT 00205010.

PMID- 17560637
TI  - Seasonal allergic rhinitis is associated with a detrimental effect on examination
      performance in United Kingdom teenagers: case-control study.
AB  - BACKGROUND: Seasonal allergic rhinitis is common globally, and symptoms have been
      shown to impair learning ability in children in laboratory conditions. Critical
      examinations in children are often held in the summer during the peak grass
      pollen season. OBJECTIVE: To investigate whether seasonal allergic rhinitis
      adversely impacts examination performance in United Kingdom teenagers. METHODS:
      Case-control analysis of 1,834 students (age 15-17 years; 50% girls) sitting for
      national examinations. Cases were those who dropped 1 or more grades in any of 3
      core subjects (mathematics, English, and science) between practice (winter) and
      final (summer) examinations; controls were those whose grades were either
      unchanged or improved. Associations between allergic rhinitis symptoms, clinician
      diagnosed allergic rhinitis, and allergic rhinitis-related medication use,
      recorded on examination days immediately before the examination, were assessed
      using multilevel regression models. RESULTS: Between 38% and 43% of students
      reported symptoms of seasonal allergic rhinitis on any 1 of the examination days.
      There were 662 cases (36% of students) and 1,172 controls. After adjustment,
      cases were significantly more likely than controls to have had allergic rhinitis
      symptoms during the examination period (odds ratio [OR], 1.4; 95% CI, 1.1-1.8; P
      = .002), to have taken any allergic rhinitis medication (OR, 1.4; 95% CI, 1.1
      1.7; P = .01), or to have taken sedating antihistamines (OR, 1.7; 95% CI, 1.1
      2.8; P = .03). CONCLUSION: Current symptomatic allergic rhinitis and rhinitis
      medication use are associated with a significantly increased risk of unexpectedly
      dropping a grade in summer examinations. CLINICAL IMPLICATIONS: This is the first
      time the relationship between symptomatic allergic rhinitis and poor examination
      performance has been demonstrated, which has significant implications for
      clinical practice.

PMID- 17560636
TI  - Social stimuli enhance phencyclidine (PCP) self-administration in rhesus monkeys.
AB  - Environmental factors, including social interaction, can alter the effects of
      drugs of abuse on behavior. The present study was conducted to examine the
      effects of social stimuli on oral phencyclidine (PCP) self-administration by
      rhesus monkeys. Ten adult rhesus monkeys (M. mulatta) were housed side by side in
      modular cages that could be configured to provide visual, auditory, and olfactory
      stimuli provided by another monkey located in the other side of a paired unit.
      During the first experiment, monkeys self-administered PCP (0.25 mg/ml) and water
      under concurrent fixed ratio (FR) 16 schedules of reinforcement with either a
      solid or a grid (social) partition separating each pair of monkeys. In the second
      experiment, a PCP concentration-response relationship was determined under
      concurrent progressive ratio (PR) schedules of reinforcement during both the
      solid and grid partition conditions. Under the concurrent FR 16 schedules, PCP
      and water self-administration were significantly higher during exposure to a cage
      mate through a grid partition than when a solid partition separated the monkeys.
      The relative reinforcing strength of PCP, as measured by PR break points, was
      greater during the grid partition condition compared to the solid partition
      condition indicated by an upward shift in the concentration-response curve. To
      determine whether the social stimuli provided by another monkey led to activation
      of the hypothalamic-pituitary-adrenal (HPA) axis, which may have evoked the
      increase of PCP self-administration during the grid partition condition, a third
      experiment was conducted to examine cortisol levels under the two housing
      conditions. A modest, but nonsignificant increase in cortisol levels was found
      upon switching from the solid to the grid partition condition. The results
      suggest that social stimulation among monkeys in adjoining cages leads to
      enhanced reinforcing strength of PCP.

PMID- 17560638
TI  - Traditional Chinese herbal remedies for asthma and food allergy.
AB  - The increasing prevalence of allergic diseases in Westernized countries is a
      significant health problem. Curative therapies for these diseases are not
      available. There are also significant concerns regarding the potential side
      effects from the chronic use of conventional drugs such as corticosteroids,
      especially in children. Many patients with chronic allergic conditions seek
      complementary and alternative medicine therapies including traditional Chinese
      medicines. This trend has begun to attract interest from mainstream health care
      providers and scientific investigators and has stimulated government agencies in
      the United States to provide support and guidance for the scientific
      investigation of complementary and alternative medicine. This effort may lead to
      improved therapies and better health care/patient outcomes. This review presents
      an update on the most promising Chinese herbal remedies for asthma and food
      allergy.

PMID- 17560639
TI  - Variations in measles vaccine-specific humoral immunity by polymorphisms in SLAM
      and CD46 measles virus receptors.
AB  - BACKGROUND: Measles infection requires 2 cellular receptors, signaling lymphocyte
      activation molecule (SLAM) and CD46. Known and novel single nucleotide
      polymorphisms (SNPs) in SLAM and CD46 genes might influence the immune response
      to measles vaccine. OBJECTIVE: We sought to identify SNP associations in SLAM and
      CD46 genes with variations in measles antibody response. METHODS: We genotyped
      known SNPs in SLAM and CD46 genes in 339 subjects vaccinated with 2 doses of
      measles-mumps-rubella vaccine. We also sequenced the measles virus-binding
      domains of SLAM and CD46 to identify novel SNPs. RESULTS: Increased
      representation of minor alleles for rs3796504 and rs164288 in the SLAM gene was
      associated with an allele dose-related decrease (4-fold) in measles-specific
      antibodies. Heterozygous genotype TC for rs12076998 located in the untranslated
      region 33 bp upstream of the measles virus-binding domain of the SLAM gene was
      associated with higher median antibody levels (1991 vs 1467 IU/L, P = .01)
      compared with wild-type TT. Within the CD46 gene, the minor allele C for intronic
      SNP (rs11118580) was associated with an allele dose-related decrease in measles
      antibodies (1072 vs 1795 IU/L, P < .01). Decreases in minor allele counts for
      rs3796504, rs164288, and rs1118580 demonstrated a significant (P < .001) additive
      effect on measles-specific antibodies. CONCLUSION: Our data suggest that specific
      SNPs present in both the SLAM and CD46 genes are associated with measurable and
      significant variations in antibody response after measles vaccination. CLINICAL
      IMPLICATIONS: Understanding the immunogenetics of measles vaccine receptors is
      important to better understand variations in immune responses to vaccines and to
      design better vaccines.

PMID- 17560640
TI  - Effect of IL-13 receptor alpha2 levels on the biological activity of IL-13
      variant R110Q.
AB  - BACKGROUND: IL-13 is a key cytokine associated with the asthmatic phenotype. IL
      13 signals via its cognate receptor, a complex of IL-13 receptor (IL-13R) alpha 1
      chain with IL-4 receptor alpha; however, a second protein, IL-13Ralpha2, also
      binds IL-13. Recently a polymorphic variant of IL-13 (R110Q) has been shown to be
      associated with atopy. OBJECTIVE: To investigate the binding properties of this
      IL-13 variant to its cognate receptors. METHODS: We used surface plasmon
      resonance to measure the binding kinetics of R110Q to its receptors. Primary
      human fibroblasts were grown from endobronchial biopsies obtained from
      volunteers. Receptor levels were measured by fluorescence-activated cell sorting.
      RESULTS: There was no significant difference in the binding of R110Q with soluble
      human IL-13Ralpha1 compared with IL-13 (32 +/- 5 nmol/L and 36 +/- 7 nmol/L,
      respectively; P = .625). However, a small but significant difference was observed
      in the binding of R110Q to soluble human IL-13Ralpha2 compared with IL-13 (840 +/
      87 pmol/L and 1.1 +/- .05 nmol/L, respectively; P = .04). We observed that
      primary human lung fibroblasts expressed different levels of IL-13Ralpha2.
      Eotaxin release from fibroblasts expressing low IL-13Ralpha2 levels was
      significantly higher in response to R110Q compared with IL-13. This was not
      evident in cells that had high baseline IL-13Ralpha2 levels. CONCLUSION: These
      results suggest that relatively small changes in functional properties of a
      ligand combined with variation in receptor levels in vivo can result in
      significant differences in responsiveness. CLINICAL IMPLICATIONS: Expression of
      R110Q and low IL-13Ralpha2 levels can result in important biological differences
      that may have clinical relevance in an atopic environment.

PMID- 17560641
TI  - Equine endometrial biopsy: enhancement of clinical value by more extensive
      histopathology and application of new diagnostic techniques?
AB  - During the 1960s and 1970s, the clinical value of equine endometrial
      histopathology was firmly established after it was shown that fertility outcome
      was correlated with the presence and severity of specific microscopic lesions.
      The objective of this paper is to summarize reports from the veterinary
      literature published after the mid 1980s that describe new diagnostic methods of
      assessing equine uterine health using material collected by endometrial biopsy.

PMID- 17560642
TI  - The DNA base excision repair protein Ape1/Ref-1 as a therapeutic and
      chemopreventive target.
AB  - With our growing understanding of the pathways involved in cell proliferation and
      signaling, targeted therapies, in the treatment of cancer are entering the
      clinical arena. New and emerging targets are proteins involved in DNA repair
      pathways. Inhibition of various proteins in the DNA repair pathways sensitizes
      cancer cells to DNA damaging agents such as chemotherapy and/or radiation. We
      study the apurinic endonuclease 1/redox factor-1 (Ape1/Ref-1) and believe that
      its crucial function in DNA repair and reduction-oxidation or redox signaling
      make it an excellent target for sensitizing tumor cells to chemotherapy. Ape1/Ref
      1 is an essential enzyme in the base excision repair (BER) pathway which is
      responsible for the repair of DNA caused by oxidative and alkylation damage. As
      importantly, Ape1/Ref-1 also functions as a redox factor maintaining
      transcription factors in an active reduced state. Ape1/Ref-1 stimulates the DNA
      binding activity of numerous transcription factors that are involved in cancer
      promotion and progression such as AP-1 (Fos/Jun), NFkappaB, HIF-1alpha, CREB, p53
      and others. We will discuss what is known regarding the pharmacological targeting
      of the DNA repair activity, as well as the redox activity of Ape1/Ref-1, and
      explore the budding clinical utility of inhibition of either of these functions
      in cancer treatment. A brief discussion of the effect of polymorphisms in its DNA
      sequence is included because of Ape1/Ref-1's importance to maintenance and
      integrity of the genome. Experimental modification of Ape1/Ref-1 activity changes
      the response of cells and of organisms to DNA damaging agents, suggesting that
      Ape1/Ref-1 may also be a productive target of chemoprevention. In this review, we
      will provide an overview of Ape1/Ref-1's activities and explore the potential of
      this protein as a target in cancer treatment as well as its role in
      chemoprevention.

PMID- 17560643
TI  - Fracture toughness of a ceramic-resin interface.
AB  - OBJECTIVES: The purpose of this study was to compare the interfacial fracture
      toughness of smooth and roughened ceramic surfaces bonded with a luting resin
      using an optimized method of silane treatment. METHODS: Ceramic discs were
      prepared with four different surface preparations (n=20) consisting of (1)
      polished, (2) gritblasted, (3) hydrofluoric acid etched and (4) gritblasted and
      etched. The ceramic discs were then covered by a PTFE tape with a chevron shaped
      circular hole. The exposed surfaces were treated by an optimized silane treatment
      followed by an unfilled resin and then a luting resin. Specimens were then stored
      in distilled water at 37 degrees C for (A) 24h and (B) 30 days. The interfacial
      fracture toughness was measured, the mode of failure and fracture surfaces were
      also examined under a stereo-zoom microscope and a scanning electron microscope.
      RESULTS: One-way ANOVA showed that there was no statistically significant
      difference in the mean interfacial fracture toughness for groups A1-A4 (P>0.05).
      However, the mean interfacial fracture toughness for group B1 was significantly
      different from that for groups B2, B3 and B4 (P<0.05). Independent-samples t-test
      results showed that there was a significant increase in the G(Ic) mean value for
      groups B2 and B3 after 30 days water storage (P<0.05). The modes of failure were
      predominantly interfacial or cohesive within the resin. SIGNIFICANCE: It can be
      concluded that micro-mechanical retention by gritblasting the ceramic surfaces
      could be sufficient with no need for HF acid etching the ceramic surfaces when an
      appropriate silane application procedure is used.

PMID- 17560644
TI  - Over-connected? A qualitative exploration of the relationship between Australian
      youth and their mobile phones.
AB  - In Australia, youth are the most prolific users of mobile phones, however, there
      is little research investigating this phenomenon. This paper reports a
      qualitative exploration of psychological factors relating to mobile phone use
      amongst Australian youth. 32 participants, aged between 16 and 24 years, took
      part in focus group discussions. Thematic data analysis focussed on identifying
      the psychological benefits arising from mobile phone use and whether mobile phone
      addiction was occurring amongst this group. Mobile phone use was believed to
      provide numerous benefits to users and is an intrinsic part of most young
      people's lives. It emerged that some young people are extremely attached to their
      mobile phone with symptoms of behavioural addiction revealed in participants'
      descriptions of their mobile phone use. The study provides a solid foundation for
      further work investigating addictive patterns of mobile phone use amongst youth.

PMID- 17560645
TI  - Kinetic analysis of nanoparticulate polyelectrolyte complex interactions with
      endothelial cells.
AB  - A non-toxic, nanoparticulate polyelectrolyte complex (PEC) drug delivery system
      was formulated to maintain suitable physicochemical properties at physiological
      pH. Toxicity, binding, and internalization were evaluated in relevant
      microvascular endothelial cells. PEC were non-toxic, as indicated by cell
      proliferation studies and propidium iodide staining. Inhibitor studies revealed
      that PEC were bound, in part, via heparan sulfate proteoglycans and internalized
      through macropinocytosis. A novel, flow cytometric, Scatchard protocol was
      established and showed that PEC, in the absence of surface modification, bind
      cells non-specifically with positive cooperativity, as seen by graphical
      transformations.

PMID- 17560646
TI  - Lipopolysaccharide (LPS) up-regulates the expression of haem oxygenase-1 in mouse
      placenta.
AB  - Haem oxygenase-1 (HO-1) is an inducible enzyme that catalyses the rate-limiting
      step in the degradation of haem to biliverdin, carbon monoxide and iron. There is
      increasing evidence that HO plays important roles in the cellular defence against
      oxidative stress and the deleterious effects of pro-inflammatory cytokines. In
      the present study, we investigated the effects of lipopolysaccharide (LPS) on the
      expression of HO-1 in mouse placenta. When a single dose of LPS (75 microg/kg,
      i.p.) was administered to the pregnant mice, the expression of HO-1 in mouse
      placenta was markedly increased at 12 h after LPS treatment and remained elevated
      up to 48 h after LPS administration. The expression of HO-2, the constitutive
      form, did not change at the various time points observed. LPS-induced up
      regulation of placental HO-1 was blocked after the pregnant mice were pre-treated
      with alpha-phenyl-N-t-butylnitrone (PBN), a free radical spin trapping agent.
      Correspondingly, PBN pre-treatment significantly inhibited LPS-induced lipid
      peroxidation and glutathione (GSH) depletion in mouse placenta. Furthermore,
      pentoxifylline (PTX), an inhibitor of tumour necrosis factor alpha (TNF-alpha)
      synthesis, also significantly attenuated LPS-induced up-regulation of placental
      HO-1. However, aminoguanidine (AG), a selective inhibitor of inducible nitric
      oxide synthase (iNOS), had little effect on LPS-induced up-regulation of HO-1 in
      mouse placenta. Taken together, these results indicate that LPS up-regulates the
      expression of HO-1 in mouse placenta. LPS-induced up-regulation of placental HO-1
      is probably mediated, at least in part, by reactive oxygen species (ROS) and TNF
      alpha, rather than nitric oxide.

PMID- 17560647
TI  - Successful treatment of extramedullary gastric plasmacytoma with the combination
      of bortezomib and dexamethasone: first reported case.
AB  - We report a case of a 68-year-old man presented with upper-gastrointestinal
      bleeding. Endoscopy showed a large ulcerated gastric mass. Histological
      examination of the gastric biopsies revealed a k monoclonal extramedullary
      plasmacytoma (EMP). Further staging was negative for multiple myeloma. The
      patient was managed with bortezomib at a dose of 1.3mg/m2 on days 1, 4, 8 and 11
      of a 21-day cycle in combination with dexamethasone 20mg p.o. on days 1, 2, 4, 5,
      8, 9 and 11, 12 of each cycle. After 4 cycles of treatment, no endoscopic or
      histological findings of EMP were found. Thirteen months after diagnosis the
      patient is in complete remission with no evidence of local relapse or evolution
      to multiple myeloma. This is the first reported case of EMP successfully managed
      with the combination of bortezomib and dexamethasone.

PMID- 17560648
TI  - Association of PIM gene translocation and TEL/AML1 rearrangement.

PMID- 17560649
TI  - Effects of CpG-oligonucleotides, poly I:C and LPS on Atlantic cod scavenger
      endothelial cells (SEC).
AB  - Carrying out a remarkably efficient clearance of colloidal and soluble
      macromolecular waste substances from the circulation, the scavenger endothelial
      cells (SECs) represent an important part of the reticuloendothelial system of
      vertebrates. It has been previously shown that these cells play an important role
      in the innate immune system by eliminating from the blood a number of molecules
      known to elicit inflammatory reactions. In the present study we have investigated
      the uptake of LPS and oligonucleotides in cultured Atlantic cod SECs, and
      determined if interaction with these pathogen associated molecules affect the
      scavenger activity and/or production of immune modulating molecules of SECs.
      Preincubation of cultured SECs with CpG (5 and 20 microg/ml) or Poly I:C (10 or
      40 microg/ml) gave selective down-regulation of scavenger receptor-mediated
      endocytosis, but only marginal effects were noted on endocytosis via the mannose-
      and collagen alpha chain receptors. Preincubation with LPS or a non-inflammatory
      ligand for the scavenger receptor did not result in altered endocytosis via any
      of the receptors tested. Only Poly I:C (40 microg/ml) was observed to increase
      the production of NO. RT-PCR analyses showed IL-1 production which was not
      increased above control after pre-treatment with two different CpG
      oligonucleotides or Poly I:C. In fact, preincubation with Poly I:C, but not CpGs,
      resulted in degradation of total intracellular RNA. In conclusion, our study
      shows that SECs respond differently to the different immunomodulators used and
      that their important clearance activity as scavenger cells can be regulated by
      the use of oligonucleotides.

PMID- 17560650
TI  - Joint effects of dietary cadmium and polychlorinated biphenyls on metallothionein
      induction, lipid peroxidation and histopathology in the kidneys and liver of bank
      voles.
AB  - Free-living bank voles have been shown to be more sensitive to cadmium (Cd)
      toxicity than the rodents exposed to Cd under laboratory conditions. The present
      study was designed to find out whether polychlorinated biphenyls (PCBs), common
      environmental co-contaminants, increase susceptibility to Cd toxicity through
      inhibition of metallothionein (MT) synthesis-a low molecular weight protein that
      is considered to be a primary intracellular component of the protective
      mechanism. For 12 weeks, the male bank voles were provided with diets containing
      Cd (0.05 microg/g (control) and 10 microg/g dry wt) and PCBs (0, 10 and 50
      microg/g dry wt) alone or in combination under long (16 h) and short (8 h)
      photoperiods. At the end of exposure period, histological examinations and
      analyses of MT, Cd, Fe and lipid peroxidation in the kidneys and liver were
      carried out. Dietary PCBs did not affect Cd inducibility of renal MT, but
      decreased it significantly in the liver; however, no signs of Cd toxicity
      (measured by histopathology) occurred in both organs. On the contrary, PCBs at
      the highest dose increased significantly lipid peroxidation in the kidneys and
      liver (4-fold) only in the bank voles raised under a long photoperiod; the PCB
      induced hepatic lipid peroxidation was accompanied by extensive histopathological
      changes including hepatocyte enlargement, necrosis and steatosis. Co-treatment
      with dietary Cd significantly suppressed the increase in lipid peroxidation and
      apparently reduced hepatic damage. These data indicate that (1) dietary PCBs do
      not enhance Cd toxicity in the kidneys and liver of bank voles and (2) dietary Cd
      suppresses PCB-induced hepatotoxicity that appears to be photoperiod-dependent.

PMID- 17560651
TI  - WITHDRAWN: Genomic evidence of porcine parvovirus (ppv) in native Indian swine.
AB  - This article has been withdrawn consistent with Elsevier Policy on Article
      Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). The Publisher
      apologizes for any inconvenience this may cause.

PMID- 17560652
TI  - Lack of TNFalpha mRNA expression in cervical cancer is not associated with loss
      of heterozygosity at 6p21.3, inactivating mutations or promoter methylation.
AB  - Infection with oncogenic human papillomavirus (HPV) is considered to be the major
      etiologic event for cervical cancer. Tumor necrosis factor alpha (TNFalpha), a
      proinflammatory cytokine, may be involved in orchestrating an antitumor immune
      response against human papillomavirus expressing cervical cancer cells. Hence,
      loss of TNFalpha could be advantageous for tumor cells to escape immune
      clearance. The aim of our study was to investigate TNFalpha gene expression and
      epigenetic characteristics associated with the loss of TNFalpha expression in
      cervical cancer. To this end, we examined TNFalpha expression, loss of
      heterozygosity (LOH) at 6p21.3, the locus of TNFalpha, mutational status of the
      TNFalpha locus, loss of the TNFalpha promoter variant 2 allele and CpG
      hypermethylation of the TNFalpha promoter. RNA in situ hybridization showed
      absence of TNFalpha expression in 45% of 63 tumors. LOH occurred in 57% of the
      tumors and was not concordant with absence of TNFalpha mRNA. No mutations in the
      TNFalpha gene were identified in 15 cases deficient in TNFalpha expression
      exhibiting LOH. Furthermore, lack of TNFalpha expression did not correlate with
      promoter methylation. In conclusion, TNFalpha mRNA expression is absent in nearly
      half of the cervical tumors analyzed. Neither promoter methylation nor genetic
      causes for lack of expression were evident.

PMID- 17560653
TI  - Iron supplementation protects against lead-induced apoptosis through MAPK pathway
      in weanling rat cortex.
AB  - Recent studies indicate that iron (Fe) is involved in neurotoxicity caused by
      inorganic lead (Pb). We studied the role of Fe in the effects Pb-induced cerebral
      apoptosis during rat development and to explore its possible regulatory
      mechanism. In the present study, weanling male Sprague-Dawley rats were randomly
      divided into four groups. Three groups of rats received 400 microg/mL Pb acetate
      solution in drinking water, among which two of the groups were concurrently given
      20mg/kg and 40mg/kg FeSO(4) solution, respectively, as the low and high Fe group,
      for 6 weeks. The Fe doses were administered orally by gavage every other day
      according to animal body weight. For the control group, Na acetate with an
      acetate concentration equivalent to the high dose of Pb acetate was prepared in
      the same manner. At the end of the study, exposure to Pb in drinking water
      significantly promoted internucleosomal DNA fragmentation, enhanced the
      percentage of TUNEL-positive cells and increased the caspase-3 activities in
      cortex as compared to the controls. At the same time, it did cause a significant
      decrease in cortex Fe concentrations. Concomitant supplement with different dose
      Fe appeared to restore brain Fe level to the normal level. Although the low dose
      of Fe restored brain Pb level to the normal level and the high dose of Fe did
      not, both of them reduced the formation of DNA fragments, showed few TUNEL
      positive cells with yellow nuclei and inhibited Pb-induced procaspase-3
      degradation. Western blot showed that exposure to Pb caused a significant
      elevation in the phosphorylation of ERK1/2, JNK1/2, and Elk-1. Low Fe
      supplemental treatment suppressed the phosphorylation of ERK1/2 and JNK1/2 but
      not Elk-1. Interestingly, high Fe treatment slightly suppressed the
      phosphorylation of JNK1/2, but significantly elevated the phosphorylation of
      ERK1/2 and Elk-1. Collectively, the current study suggests that supplementation
      of Fe during Pb treatment prevents against cytotoxicity and apoptosis induced by
      Pb insults, in which MAPK pathways play an important role in Pb-induced cerebral
      apoptosis by activating the MEK-ERK pathway that suppresses JNK signaling.

PMID- 17560654
TI  - Specific sensing of poly G by the aluminum-salophen complex.
AB  - The Al(III)-salophen complex 1 exhibited strong spectroscopic changes
      specifically upon addition of polyG and GpG, while double stranded DNA and RNA,
      and single stranded polyA, polyU and polyC induced negligible spectral changes of
      1. Titrations with mono-nucleotides yielded no spectroscopic changes, revealing
      that there must be at least two consecutive guanines in single stranded
      oligonucleotide structure for a measurable spectroscopic change of 1. Preliminary
      results show that 1 has moderate antiproliferative effect on a number of human
      tumour cell lines.

PMID- 17560655
TI  - Trends in candidemia and antifungal susceptibility in a university hospital in
      Northern Ireland 2001-2006.
AB  - OBJECTIVES: To describe the species distribution and antifungal susceptibility
      trends for documented episodes of candidemia at the Royal Hospitals, Belfast,
      2001-2006. METHODS: Laboratory-based retrospective observational study of all
      episodes of candidemia. RESULTS: There were 151 episodes of candidemia. The
      species recovered were: 96 C. albicans; 26 C. glabrata; 18 C. parapsilosis; five
      C. tropicalis; four C. guilliermondii; one C. famata and one C. dubliniensis. We
      separated the data into two periods 2001-2003 and 2004-2006; contrary to the
      findings of other investigators, there was a notable trends toward increasing
      frequency of C. albicans and decreasing frequency of non-albicans species over
      time. Although the proportion of C. albicans, C. parapsilosis and C. tropicalis
      isolates susceptible to fluconazole was unchanged over time, a trend of decreased
      susceptibility of C. glabrata to fluconazole was noted over the six-year period.
      Overall, 73% and 7.7% of C. glabrata isolates had susceptible-dose-dependent and
      resistant phenotypes, respectively. The percentage of C. glabrata isolates
      susceptible to fluconazole (MIC <8 microg/ml) decreased from 36% in 2001-2003 to
      0% in 2004-2006. Flucytosine resistance was detected in only 4 (2.7%) isolates.
      None of the isolates had an amphotericin B MIC <1 microg/ml. CONCLUSION: A shift
      towards increasing dominance of C. albicans contrasts both with reports from
      other countries and previous data from Northern Ireland. Upwards fluconazole MIC
      drift among C. glabrata has important implications for empirical therapeutic
      decisions.

PMID- 17560656
TI  - Measles outbreaks in high schools closely associated with sporting events in
      Niigata, Japan.
AB  - OBJECTIVES: Due to high vaccine coverage in Niigata, we had no outbreaks of
      measles from 1997 to 2003 but an opportunity to study the role of sporting events
      in the propagation of an epidemic was experienced in the spring of the latter
      year. METHODS: Mandatory measles case reports were requested from all high
      schools in Niigata, which covered a school year, date of onset, club activity,
      vaccination status, and hospitalization. RESULTS: With national marathon and
      kendo (Japanese fencing) meetings for high school students, measles outbreaks
      occurred at 27 high schools with 192 patients (186 students and 6 teachers) in
      Niigata. Of 64 unvaccinated patients, 14 (21.9%) were hospitalized and 6 (6.2%)
      of 97 vaccinated patients. Mostly single cases were encountered at high schools
      in which index cases had a vaccination history, whereas at a high school in which
      index cases had no vaccination history, the total number of cases per school
      increased, mostly within more than 3 cases (p<0.05). CONCLUSION: We conclude that
      sporting events, even if outdoors, might be a risk factor for measles infections.
      Appropriate actions to control outbreaks should be performed promptly in
      collaboration with related personnel and institutions.

PMID- 17560657
TI  - Neurosteroid binding sites on GABA(A) receptors.
AB  - Controlling neuronal excitability is vitally important for maintaining a healthy
      central nervous system (CNS) and this relies on the activity of type A gamma
      aminobutyric acid (GABA(A)) neurotransmitter receptors. Given this role, it is
      therefore important to understand how these receptors are regulated by endogenous
      modulators in the brain and determine where they bind to the receptor. One of the
      most potent groups of modulators is the neurosteroids which regulate the activity
      of synaptic and extrasynaptic GABA(A) receptors. This level of regulation is
      thought to be physiologically important and its dysfunction may be relevant to
      numerous neurological conditions. The aim of this review is to summarise those
      studies that over the last 20 years have focussed upon finding the binding sites
      for neurosteroids on GABA(A) receptors. We consider the nature of steroid binding
      sites in other proteins where this has been determined at atomic resolution and
      how their generic features were mapped onto GABA(A) receptors to help locate 2
      putative steroid binding sites. Altogether, the findings strongly suggest that
      neurosteroids do bind to discrete sites on the GABA(A) receptor and that these
      are located within the transmembrane domains of alpha and beta receptor subunits.
      The implications for neurosteroid binding to other inhibitory receptors such as
      glycine and GABA(C) receptors are also considered. Identifying neurosteroid
      binding sites may enable the precise pathophysiological role(s) of neurosteroids
      in the CNS to be established for the first time, as well as providing
      opportunities for the design of novel drug entities.

PMID- 17560658
TI  - The butterfly and the loom.
AB  - The relationship between structure and function in the brain has an interesting
      counterpart in the scientific relationship of Santiago Ramon y Cajal and Charles
      Sherrington. In their search for the principles of organization of the nervous
      system, both men met at the synapse. For Sherrington, who coined the word
      'synapse', the neuron was the functional unit that integrated excitatory and
      inhibitory input. For Cajal, the synapse was the explanation for how neurons
      could be individual elements, yet connected to form circuits. Both men were
      primarily concerned with local circuits in spinal cord and brain, but
      imaginatively extrapolated their discoveries on simple circuits to higher
      cognitive functions. Both men wrote poetically about their discoveries and so
      provided neuroscience with a rich vocabulary, vivid and memorable images, and
      concepts that remain part of the currency of 21st century neuroscience.

PMID- 17560659
TI  - Three-dimensional reconstruction of stained histological slices and 3D non-linear
      registration with in-vivo MRI for whole baboon brain.
AB  - The correlation between post-mortem data and in-vivo brain images is of high
      interest for studying neurodegenerative diseases. This paper describes a protocol
      that matches a series of stained histological slices of a baboon brain with an
      anatomical MRI scan of the same subject using an intermediate 3D-consistent
      volume of "blockface" photographs taken during the sectioning process. Each
      stained histological section of the baboon brain was first registered to its
      corresponding blockface photograph using a novel "hemi-rigid" transformation.
      This piecewise rigid 2D transformation was specifically adapted to the
      registration of slices which contained both hemispheres. Subsenquently, to
      correct the global 3D deformations of the brain caused by histological
      preparation and fixation, a 3D elastic transformation was estimated between the
      blockface volume and the MRI data. This 3D elastic transformation was then
      applied to the histological volume previously aligned using the hemi-rigid method
      to complete the registration of the series of stained histological slices with
      the MRI data. We assessed the efficacy of our method by evaluating the quality of
      matching of anatomical features as well as the difference of volume measurements
      between the MRI and the histological images. Two complete baboon brains (with the
      exception of cerebellum) were successfully processed using our protocol.

PMID- 17560660
TI  - Reliability of the microdialysis pump CMA 107 under hyperbaric conditions.
AB  - OBJECTIVE: Microdialysis measurements of extracellular substances under
      hyperbaric conditions were manifold used in several investigations. However, to
      our knowledge there is no analysis, which verified the applicability of
      microdialysis pumps under hyperbaric conditions. Thus, a goal of this study was
      to investigate the reliability of the microdialysis pump (MDP) CMA 107 in a
      hyperbaric environment up to 2.4bar absolute pressure. METHODS: The CMA 107 with
      a perfusion rate of 2microL/min was stored in a decompression chamber. The
      ambient pressure was increased from 1 to 2.4bar absolute within 15min, maintained
      for 90min and then decreased to 1bar within 15min. The vials were changed every
      15min, weighed before as well as after collecting the sample volume and the
      absolute recovery of glutamate, pyruvate, lactate, glucose and glycerol was
      determined. The same setup was performed under normobaric conditions. RESULTS:
      The pumping capacity was 1.7% greater than expected under normobaric conditions,
      36.5% less than expected in the compression phase, 10.5% less than expected in
      the isopression phase and 26.3% greater than expected in the decompression phase
      under hyperbaric conditions. The absolute recoveries under hyperbaric conditions
      were affected during the isopression phase with a deviation from -6 to +20%
      compared to normobaric environments. CONCLUSION: The study demonstrated that an
      absolute ambient pressure up to 2.4bar did influence the pumping capacity and the
      reliability of the absolute recovery. These results need to be taken into
      consideration when interpreting microdialysis studies performed under hyperbaric
      conditions.

PMID- 17560661
TI  - Intracellular long-wavelength voltage-sensitive dyes for studying the dynamics of
      action potentials in axons and thin dendrites.
AB  - In CNS neurons most of synaptic integration takes place in thin dendritic
      branches that are difficult to study with conventional physiological recording
      techniques (electrodes). When cellular compartments are too small, or too many,
      for electrode recordings, optical methods bring considerable advantages. Here we
      focused our experimental effort on the development and utilization of new kinds
      of voltage-sensitive dyes (VSD). The new VSDs have bluish appearance in organic
      solvents, and hence are dubbed "blue dyes". They have preferred excitation
      windows for voltage recording that are shifted to longer wavelengths
      (approximately 660nm). Excitation in deep red light and emission in the near
      infrared render "blue VSDs" potentially useful in measurements from fluorescent
      structures below the tissue surface because light scattering is minimized at
      longer wavelengths. Seven new molecules were systematically tested using
      intracellular injection. In comparison to the previously used red dye (JPW-3028)
      the blue dyes have better sensitivity (DeltaF/F) by approximately 40%. Blue dyes
      take little time to fill the dendritic tree, and in this aspect they are
      comparable with the fastest red dye JPW-3028. Based on our results, blue VSDs are
      well suited for experimental exploration of thin neuronal processes in semi
      intact preparations (brain slice). In some cases only six sweeps of temporal
      averaging were needed to acquire excellent records of individual action
      potentials in basal and oblique dendritic branches, or in axons and axon
      collaterals up to 200microm away from the cell body. Signal-to-noise ratio of
      these recordings was approximately 10. The combination of blue dyes and laser
      illumination approach imposed little photodynamic damage and allowed the total
      number of recording sweeps per cell to exceed 100. Using these dyes and a spot
      laser illumination technique, we demonstrate the first recording of action
      potentials in the oblique dendrite and distal axonal segment of the same
      pyramidal cell.

PMID- 17560662
TI  - Early, microbially driven follicular reactions in the neonatal piglet do not
      contribute to expansion of the immunoglobulin heavy chain V-D-J repertoire.
AB  - Selective microbial colonisation of germ-free piglets is reported to result in
      expansion of immunoglobulin V(H)- and D(H)-segment usage from an initially
      limited repertoire. Here, the response of the palatine tonsil to microbial
      colonisation was compared in age-matched conventionally reared and germ-free
      piglets. At 3 and 5 days after birth an expansion in the B-cell follicle area was
      observed in the conventional, microbially colonised animals, which was not seen
      in the germ-free piglets. Consistent with this observation, sequencing of re
      arranged heavy chain V-D-J units demonstrated accumulation of point mutations
      indicating somatic hypermutation in the conventional, microbially colonised
      piglets but not in the germ-free animals. However, V(H)- and D(H)-segment usage
      and CDR3 length did not differ between the groups. The results suggest that the
      follicle reaction observed occurs in response to microbial challenge, involves
      proliferation and somatic hypermutation of B-cells but does not expand repertoire
      or generate classical, isotype-switched memory B-cells. We suggest that microbial
      colonisation of neonatal piglets drives immunological competence in two stages:
      first, an antigen non-specific, follicular reaction which expands immunological
      compartments; and second, microbe driven changes in V-segment usage which expand
      immunological repertoire.

PMID- 17560663
TI  - A study of the factors inducing the development of childhood-onset myasthenia
      gravis using CDR3 spectratyping analysis of the TCR repertoire.
AB  - Myasthenia gravis (MG) is an autoimmune disease. AChR-specific autologous helper
      T (Th) cells are essential to the pathogenesis of MG. Factors correlated with the
      development of childhood-onset MG are unknown. In longitudinal studies, we found
      TCR Vbeta 2/5.1/6/7 usage in the development or relapse phases, but not in the
      remission phase. We also found that TCR Vbeta 8/9/13.1/15/18/20 usage persisted.
      The polyclonally expanded TCR Vbeta 2/5.1/6/7 by CDR3 spectratyping was found to
      be associated with the development of disease. These data suggest that in
      patients with childhood-onset MG, stimuli such as superantigens induced by a
      preceding infection, which cause development of the polyclonal pattern in TCR
      Vbeta families, play an important role in the development of the disease.

PMID- 17560664
TI  - Is acetaminophen as effective as an antihistamine-decongestant-acetaminophen
      combination in relieving symptoms of acute nasopharyngitis in children? A
      randomised, controlled trial.
AB  - OBJECTIVES: To determine the efficiency of drugs, which include antihistaminic
      decongestant-acetaminophen agents versus only acetaminophen in symptomatic
      treatment of acute nasopharyngitis in children. METHODS: This clinical,
      randomized, controlled, single blind drug efficacy comparison research was
      conducted in 148 patients with acute nasopharyngitis between ages 2 and 12 years.
      After randomization, Group-1 consisted of cases (n: 86), which used OTC drugs
      [acetaminophen+diphenhydramine+pseudoephedrin] and Group-2 consisted of cases (n:
      62), which used only acetaminophen. After receiving nasal swab for showing the
      viral etiology, symptoms were scored clinically on admission and then on 10 days
      follow-up period, and re-evaluated on the third and fifth days of the drug
      therapy with the same scoring scale. Any complications were noted during the 1
      month follow-up period after taking the drugs. RESULTS: The virus isolation rate
      in Group-1 was 27.9% and in Group-2 was 22.6%. At the first day of study, before
      medication, clinic scores of the groups did not show a significant difference
      (Group-1 1.7 versus Group-2 2.0). Clinic scores in both groups on the third
      (Group-1 4.0 versus Group-2 4.1) and fifth days of therapy (Group-1 1.7 versus
      Group-2 2.0) were not different either. Also, the complication rate was not
      different during the 1-month follow-up period (Group-1 2.3% versus Group-2 8.0%,
      p: 0.12). The family response for the drug satisfaction in both groups was
      similar and positive. CONCLUSION: For relieving symptoms of acute nasopharyngitis
      in children, acetaminophen without any combination is as effective as OTC drugs
      containing acetaminophen, decongestant, and antihistaminics.

PMID- 17560665
TI  - Can zinc be an adjuvant therapy for juvenile onset recurrent respiratory
      papillomatosis?
AB  - OBJECTIVES: To report a severe case of juvenile onset recurrent respiratory
      papillomatosis (JORRP) controlled by zinc replacement therapy. To review the
      contemporary adjuvant therapies used in JORRP. METHODS: The trial of zinc was
      described in terms of its effect on the inter-surgical interval, site score and
      clinical symptoms. Long-term follow-up with dose adjustment was detailed.
      Articles reporting trials of adjuvant therapies over the past 20 years were
      reviewed in terms of regimen used, mode of assessment, side effects and final
      outcome. RESULTS: Zinc was effective in decreasing the severity of the disease,
      the rate of relapse and the need for surgery. There was an obvious relation
      between the dose used and the degree of improvement. Prolonged treatment seems to
      be needed to sustain the positive effect. No side effects were noticed over a 45
      month follow-up period. The literature does support the role of zinc in
      modulating the immune system. Eight adjuvant therapies were reviewed as published
      in 40 reports. Interferon was the most used substance. It is definitely effective
      but often associated with relapse upon discontinuation. The effect of cidofovir
      was favorable yet not dramatic as initially expected. Other less commonly used
      therapies showed humble effects. The HspE7 vaccine seems to be promising awaiting
      further trials. CONCLUSIONS: Zinc replacement therapy may benefit JORRP patients
      with zinc deficiency and should be investigated in more cases. Several adjuvant
      therapies are available for use in JORRP. They are generally beneficial though
      mostly not curative.

PMID- 17560666
TI  - Antiviral activity of carbohydrate-binding agents against Nidovirales in cell
      culture.
AB  - Coronaviruses are important human and animal pathogens, the relevance of which
      increased due to the emergence of new human coronaviruses like SARS-CoV, HKU1 and
      NL63. Together with toroviruses, arteriviruses, and roniviruses the coronaviruses
      belong to the order Nidovirales. So far antivirals are hardly available to combat
      infections with viruses of this order. Therefore, various antiviral strategies to
      counter nidoviral infections are under evaluation. Lectins, which bind to N
      linked oligosaccharide elements of enveloped viruses, can be considered as a
      conceptionally new class of virus inhibitors. These agents were recently
      evaluated for their antiviral activity towards a variety of enveloped viruses and
      were shown in most cases to inhibit virus infection at low concentrations.
      However, limited knowledge is available for their efficacy towards nidoviruses.
      In this article the application of the plant lectins Hippeastrum hybrid
      agglutinin (HHA), Galanthus nivalis agglutinin (GNA), Cymbidium sp. agglutinin
      (CA) and Urtica dioica agglutinin (UDA) as well as non-plant derived pradimicin-A
      (PRM-A) and cyanovirin-N (CV-N) as potential antiviral agents was evaluated.
      Three antiviral tests were compared based on different evaluation principles:
      cell viability (MTT-based colorimetric assay), number of infected cells
      (immunoperoxidase assay) and amount of viral protein expression (luciferase-based
      assay). The presence of carbohydrate-binding agents strongly inhibited
      coronaviruses (transmissible gastroenteritis virus, infectious bronchitis virus,
      feline coronaviruses serotypes I and II, mouse hepatitis virus), arteriviruses
      (equine arteritis virus and porcine respiratory and reproductive syndrome virus)
      and torovirus (equine Berne virus). Remarkably, serotype II feline coronaviruses
      and arteriviruses were not inhibited by PRM-A, in contrast to the other viruses
      tested.

PMID- 17560667
TI  - The copepod Tigriopus: a promising marine model organism for ecotoxicology and
      environmental genomics.
AB  - There is an increasing body of evidence to support the significant role of
      invertebrates in assessing impacts of environmental contaminants on marine
      ecosystems. Therefore, in recent years massive efforts have been directed to
      identify viable and ecologically relevant invertebrate toxicity testing models.
      Tigriopus, a harpacticoid copepod has a number of promising characteristics which
      make it a candidate worth consideration in such efforts. Tigriopus and other
      copepods are widely distributed and ecologically important organisms. Their
      position in marine food chains is very prominent, especially with regard to the
      transfer of energy. Copepods also play an important role in the transportation of
      aquatic pollutants across the food chains. In recent years there has been a
      phenomenal increase in the knowledge base of Tigriopus spp., particularly in the
      areas of their ecology, geophylogeny, genomics and their behavioural, biochemical
      and molecular responses following exposure to environmental stressors and
      chemicals. Sequences of a number of important marker genes have been studied in
      various Tigriopus spp., notably T. californicus and T. japonicus. These genes
      belong to normal biophysiological functions (e.g. electron transport system
      enzymes) as well as stress and toxic chemical exposure responses (heat shock
      protein 20, glutathione reductase, glutathione S-transferase). Recently, 40,740
      expressed sequenced tags (ESTs) from T. japonicus, have been sequenced and of
      them, 5,673 ESTs showed significant hits (E-value, >1.0E-05) to the red flour
      beetle Tribolium genome database. Metals and organic pollutants such as
      antifouling agents, pesticides, polycyclic aromatic hydrocarbons (PAH) and
      polychrlorinated biphenyls (PCB) have shown reproducible biological responses
      when tested in Tigriopus spp. Promising results have been obtained when Tigriopus
      was used for assessment of risk associated with exposure to endocrine-disrupting
      chemicals (EDCs). Application of environmental gene expression techniques has
      allowed evaluation of transcriptional changes in T. japonicus with the ultimate
      aim of understanding the mechanisms of action of environmental stressors. Through
      a better understanding of toxicological mechanisms, ecotoxicologists may use this
      ecologically relevant species in risk assessment studies in marine systems. The
      combination of uses as a whole-animal bioassay and gene expression studies
      indicate that Tigriopus may serve as an excellent tool to evaluate the impacts of
      marine pollution throughout the coastal region. The purpose of this review is to
      illustrate the potential of using Tigriopus to fulfill the niche as an important
      invertebrate marine model organism for ecotoxicology and environmental genomics.
      In addition, the knowledge gaps and areas for further studies have also been
      discussed.

PMID- 17560669
TI  - A facelift for the general transcription factor TFIIA.
AB  - TFIIA was classified as a general transcription factor when it was first
      identified. Since then it has been debated to what extent it can actually be
      regarded as "general". The most notable feature of TFIIA is the proteolytical
      cleavage of the TFIIAalphabeta into a TFIIAalpha and TFIIAbeta moiety which has
      long remained a mystery. Recent studies have showed that TFIIA is cleaved by
      Taspase1 which was initially identified as the protease for the proto-oncogene
      MLL. Cleavage of TFIIA does not appear to serve as a step required for its
      activation as the uncleaved TFIIA in the Taspase1 knock-outs adequately support
      bulk transcription. Instead, cleavage of TFIIA seems to affect its turn-over and
      may be a part of an intricate degradation mechanism that allows fine-tuning of
      cellular levels of TFIIA. Cleavage might also be responsible for switching
      transcription program as the uncleaved and cleaved TFIIA might have distinct
      promoter specificity during development and differentiation. This review will
      focus on functional characteristics of TFIIA and discuss novel insights in the
      role of this elusive transcription factor.

PMID- 17560670
TI  - Tyrosine phosphorylation of beta2-chimaerin by Src-family kinase negatively
      regulates its Rac-specific GAP activity.
AB  - beta2-Chimaerin, an intracellular receptor for the second messenger
      diacylglycerol and phorbol esters, is a GTPase-activating protein (GAP) specific
      for Rac. beta2-Chimaerin negatively controls many Rac-dependent
      pathophysiological events including tumor development. However, the regulatory
      mechanism of beta2-chimaerin remains largely unknown. Here we report that beta2
      chimaerin is tyrosine-phosphorylated by Src-family kinases (SFKs) upon cell
      stimulation with epidermal growth factor (EGF). Mutational analysis identified
      Tyr-21 in the N-terminal regulatory region as a major phosphorylation site.
      Intriguingly, the addition of SFK inhibitor and the replacement of Tyr-21 with
      Phe (Y21F) markedly enhanced Rac-GAP activity of beta2-chimaerin in EGF-treated
      cells. Moreover, the Y21F mutant inhibited integrin-dependent cell spreading, in
      which Rac1 plays a critical role, more strongly than wild-type beta2-chimaerin.
      These results suggest Tyr-21 phosphorylation as a novel, SFK-dependent mechanism
      that negatively regulates beta2-chimaerin Rac-GAP activity.

PMID- 17560671
TI  - Noninvasive imaging of anomalous coronary arteries.
AB  - Anomalous coronary arteries are a rare but recognized cause of myocardial
      ischemia and sudden death. Most patients with coronary anomalies remain
      asymptomatic because the anomaly either does not produce any symptoms during life
      or the first manifestation is sudden death. Noninvasive imaging plays crucial
      role in diagnosis of the potentially life threatening coronary anomalies.

PMID- 17560672
TI  - A case with heterotaxy reaching the Fontan procedure after unifocalizations.
AB  - One patient with major aorto-pulmonary collateral arteries and heterotaxy
      underwent staged unifocalizations, and eventually the staged Fontan completion.
      Subsequent to the bidirectional Glenn procedure, the left pulmonary artery was
      once thrombozed, but successfully treated. The progressively regurgitant common
      atrioventricular valve needed repair twice during the course. Pulmonary arterial
      pressure was 11 mm Hg 1 year after the Fontan procedure.

PMID- 17560668
TI  - Expressed sequence tag (EST) analysis of the pine wood nematode Bursaphelenchus
      xylophilus and B. mucronatus.
AB  - Most Bursaphelenchus species feed on fungi that colonise dead or dying trees.
      However, Bursaphelenchus xylophilus is unique in that in addition to feeding on
      fungi it has the capacity to be a parasite of live pine trees. We present an
      analysis of over 13,000 expressed sequence tags (ESTs) from B. xylophilus and, by
      way of contrast, over 3000 ESTs from a closely related species that does not
      parasitise plants as readily; B. mucronatus. Four libraries from B. xylophilus,
      from a variety of life stages including fungal feeding nematodes, nematodes
      extracted from plants and dauer-like stage nematodes, and one library from B.
      mucronatus were constructed and used to generate ESTs. Contig analysis showed
      that the 13,327 B. xylophilus ESTs could be grouped into 2110 contigs and 4377
      singletons giving a total of 6487 identified genes. Similarly the 3193 B.
      mucronatus ESTs yielded a total of 2219 identified genes from 425 contigs and
      1794 singletons. A variety of proteins potentially important in the parasitic
      process of B. xylophilus and B. mucronatus, including plant and fungal cell wall
      degrading enzymes and a novel gene potentially encoding a expansin-like protein
      that may disrupt non-covalent bonds in the plant cell wall were identified in the
      libraries. Additionally several gene candidates potentially involved in dauer
      entry or maintenance were also identified in the EST dataset. The EST sequences
      from this study will provide a solid base for future research on the biology,
      pathogenicity and evolutionary history of this nematode group.

PMID- 17560673
TI  - Abnormalities on cardiac planar projection and tomographic images: focus on
      pericardial effusions.
AB  - Careful, systematic inspection of planar projection and tomographic images is
      essential as extracardiac findings and non-perfusion abnormalities may be present
      and on occasion account for the patient's symptoms. Two case histories and the
      corresponding images are presented below in which a stress myocardial perfusion
      single photon emission computed tomography (SPECT) study was performed and the
      diagnosis of a pericardial effusion was made. Although pericardial effusions are
      typically diagnosed by other imaging modalities (echocardiography and computed
      tomography) they can also be identified by radionuclide imaging techniques.
      Findings on planar projection and gated SPECT include the appearance of a "halo"
      of reduced tracer concentration surrounding the heart on both the rest and stress
      planar projection and tomographic images, and a "rocking" motion of the heart on
      gated images.

PMID- 17560674
TI  - Exploring the role of HIF-1 in early angiogenesis and response to radiotherapy.
AB  - The objective of this review is to examine the role that HIF-1 plays in the
      initiation of angiogenesis and in radiotherapy response. Although these two
      phenomena may at first seem unrelated, there are parallelisms to be drawn
      associated with the importance of reactive oxygen species in controlling the
      transcriptional activity of HIF-1, independently of its main driving force,
      hypoxia. Knowledge of the mechanisms underlying the control of HIF-1 leads to
      rationale for its inhibition in a range of clinical scenarios.

PMID- 17560675
TI  - TGFbeta-1 dependent fast stimulation of ATM and p53 phosphorylation following
      exposure to ionizing radiation does not involve TGFbeta-receptor I signalling.
AB  - BACKGROUND AND PURPOSE: It has been proposed that radiation induced stimulation
      of ATM and downstream components involves activation of TGFbeta-1 and that this
      may be due to TGFbeta-1-receptor I-Smad signalling. Therefore, the aim of this
      study was to clarify the distinct role of TGFbeta-1-receptor I-Smad signalling in
      mediating ATM activity following radiation exposure. MATERIALS AND METHODS: A549
      cells were stably transfected with a conditionally regulatable TGFbeta-1
      antisense construct (Tet-on-system) to test clonogenic activity following
      irradiation. Phosphorylation profile of ATM, p53, and chk2 was determined in non
      cycling, serum-starved cells by immunoblotting. Likewise, A549 wild type cells
      were used to identify cell cycle distribution as a function of irradiation with
      or without pretreatment with CMK, a specific inhibitor of furin protease involved
      in activation of latent TGFbeta-1. Furthermore Western and immunoblot analyses
      were performed on serum-starved cells to investigate the dependence of ATM- and
      p53-stimulation on TGFbeta-1-receptor I-Smad signalling by applying a specific
      TGFbeta-1-receptor I inhibitor. RESULTS: Knock down of TGFbeta-1 by an antisense
      construct significantly increased clonogenic cell survival following exposure to
      ionizing radiation. Likewise, CMK treatment diminished the radiation induced G1
      arrest of A549 cells. Moreover, both TGFbeta-1-knock down as well as CMK
      treatment inhibited the fast post-radiation phosphorylation of ATM, p53, and
      chk2. However, as shown by the use of a specific inhibitor TGFbeta-1-receptor I
      Smad signalling was not involved in this fast activation of ATM and p53.
      CONCLUSIONS: We confirm that TGFbeta-1 plays a critical role in the stimulation
      of ATM- and p53 signalling in irradiated cells. However, this fast stimulation
      seems not to be dependent on activation of TGFbeta-1-receptor I-Smad signalling
      as recently proposed.

PMID- 17560676
TI  - Patterns of failure in children with medulloblastoma treated with 3D conformal
      radiotherapy.
AB  - BACKGROUND AND PURPOSE: Craniospinal irradiation for medulloblastoma is one of
      the most complex techniques employed in radiotherapy. Many reports stress the
      impact of irradiation quality on survival in these patients. Our report presents
      the outcome and patterns of failure for 95 patients treated with 3D conformal
      radiotherapy (3D-CRT). MATERIALS AND METHODS: From 1998 to 2003, 95 children with
      medulloblastoma received 3D conformal radiotherapy. All of them were previously
      treated with surgery and chemotherapy. The brain and upper spinal cord were
      treated with two lateral 6MV photon fields. In four patients, the cribriform
      plate was irradiated by the additional field. For primary tumour bed we applied
      two or three photon beams. Spinal cord was irradiated either with 18-20MeV
      electron fields or with a mixed beam. RESULTS: With a median follow-up of 48
      months, 32/95 patients suffered a multifocal (21) or isolated (11) recurrence. We
      evaluated every primary site of failure. In all patients, the recurrence appeared
      within the isodose level of 95-100%. CONCLUSIONS: Patterns of failure in
      medulloblastoma patients treated with 3D conformal radiotherapy indicated that
      the relapse was mainly associated with poor response to pre-irradiation
      chemotherapy. We believe that 3D conformal radiotherapy allows avoiding failures,
      related to radiotherapy uncertainties.

PMID- 17560677
TI  - The role of CCR5/CXCR3 expressing CD8+ cells in liver damage and viral control
      during persistent hepatitis C virus infection.
AB  - BACKGROUND/AIMS: CXCR3 and CCR5 play a major role in recruiting cytotoxic T cells
      (Tc) and secreting secondary type 1 cytokines (Tc1) in the liver. HCV could
      impair their expression as a survival mechanism. The role of these chemokine
      receptors on CD8+ cells in chronic hepatitis C is analysed. METHODS: Serum,
      chemokines, peripheral blood and intrahepatic lymphocytes from chronic hepatitis
      C patients were studied. CXCR3/CCR5 expressing CD8+ cells were quantified by flow
      cytometry. Serum chemokines concentration (CXCL10/CCL3) was measured by ELISA.
      Basal data were correlated with liver inflammation. Longitudinal data were
      obtained during treatment and correlated with virologic response. RESULTS:
      CCR5/CXCR3 expressing CD8+ cells were enriched in the liver and correlated with
      inflammation. Chronic HCV patients presented the same frequency of
      CCR5(high)/CXCR3(high) expressing CD8+ cells in peripheral blood as in healthy
      controls but higher serum concentration of CXCL10/CCL3. Treatment with PEG
      interferon alpha-2b plus ribavirin increased CCR5(high)/CXCR3(high) expressing
      CD8+ cells frequency in peripheral blood and decreased CXCL10/CCL3 serum
      concentration. Increase in CXCR3(high) expressing CD8+ cells after 24 weeks of
      treatment was correlated with SVR. CONCLUSIONS: In chronic hepatitis C, anti
      viral treatment induces an increase in CD8+ cells expressing chemokine receptors
      associated with Tc1 response and a reduction in their ligands. Achievement of
      viral control is associated with an increase in CXCR3(high) expressing CD8+ cells
      during treatment.

PMID- 17560678
TI  - Pioglitazone treatment increases whole body fat but not total body water in
      patients with non-alcoholic steatohepatitis.
AB  - BACKGROUND/AIMS: Non-Alcoholic Steatohepatitis (NASH) is a chronic liver disease
      frequently associated with insulin resistance and type 2 diabetes mellitus
      (T2DM). Pioglitazone reverses the metabolic and histological abnormalities of
      patients with impaired glucose tolerance or T2DM and NASH, but also leads to
      weight gain. To understand the nature of weight gain associated with pioglitazone
      treatment in NASH we analyzed 35 patients who completed tests for determination
      of whole body fat (WBF) and total body water (TBW). METHODS: Twenty-one patients
      received pioglitazone and 14 placebo in a double-blind, randomized fashion for a
      period of 6 months. WBF and TBW were measured before and after treatment using
      DXA, a water dilution technique and bioimpedance. RESULTS: Pioglitazone increased
      body weight (from 93.6+/-4.2 to 96.1+/-4.5 kg, p<0.003) and WBF measured with DXA
      (from 32.9+/-2.1 to 35.4+/-2.5 kg, p<0.002) while no changes were seen with
      placebo. Total body water was not altered significantly either after pioglitazone
      (from 45.4+/-2.3 to 45.6+/-2.7 l, p=NS) or placebo. Muscle hydration and
      extracellular water were unchanged both by pioglitazone and placebo treatments.
      CONCLUSIONS: Six months of pioglitazone treatment in patients with NASH is
      associated with weight gain that is attributable to an increase in adipose tissue
      mass and not to water retention.

PMID- 17560680
TI  - Noradrenalin vs terlipressin in patients with hepatorenal syndrome: a
      prospective, randomized, unblinded, pilot study.
AB  - BACKGROUND/AIMS: Treatment of hepatorenal syndrome (HRS) is based on
      vasoconstrictors. Terlipressin is the one with the soundest evidence.
      Noradrenalin has been suggested as an effective alternative. The current study
      was aimed at assessing the efficacy and safety of noradrenalin vs terlipressin in
      patients with HRS. METHODS: Twenty-two consecutive cirrhotic patients with HRS (9
      with HRS type 1; 13 with HRS type 2) were included. Patients were randomly
      assigned to be treated with noradrenalin (0.1-0.7 microg/kg/min) and albumin (10
      patients) or with terlipressin (1-2 mg/4h) and albumin (12 patients). Treatment
      was administered until HRS reversal or for a maximum of two weeks. Patients were
      followed-up until liver transplantation or death. RESULTS: Reversal of HRS was
      observed in 7 of the 10 patients (70%) treated with noradrenalin and in 10 of the
      12 patients (83%) treated with terlipressin, p=ns. Treatment led in both groups
      to a significant improvement in renal and circulatory function. No patient
      developed signs of myocardial ischemia. CONCLUSIONS: Data from this unblinded,
      pilot study suggest that noradrenalin is as effective and safe as terlipressin in
      patients with HRS. These results would support the use of noradrenalin, a cheap
      and widely available drug, in the management of these patients.

PMID- 17560681
TI  - Methodologic issues with transfer of ultrasound-based transient elastography into
      clinical practice.

PMID- 17560682
TI  - Nonalcoholic fatty liver disease in women with polycystic ovary syndrome.
AB  - BACKGROUND/AIMS: Insulin resistance is a common feature of both nonalcoholic
      fatty liver disease (NAFLD) and polycystic ovary syndrome (PCOS), therefore, we
      hypothesize that PCOS and NAFLD may coexist. The aim of the present study was to
      determine the frequency and characteristics of NAFLD in women with PCOS. METHODS:
      A prospective study of patients with PCOS and no current pharmacological
      treatment was conducted. NAFLD was diagnosed by abdominal ultrasound following
      exclusion of alcohol consumption, viral, or autoimmune liver disease.
      Anthropometric variables, serum levels of glucose, insulin, lipids and
      aminotransferases, and HOMA index were determined. RESULTS: Forty-one PCOS
      patients (mean age: 24.6+/-7.2yr, mean body mass index [BMI]: 30.3+/-7.0kg/m(2))
      were included; 26 of 41 PCOS patients (63.4%) had insulin resistance and 17
      (41.5%) had NAFLD. Nine of the NAFLD patients (64%) also had abnormal
      aminotransferases. Women with NAFLD and PCOS had a higher HOMA index and a higher
      waist-hip ratio than those with normal ultrasound. Patients with PCOS showed a
      higher frequency of NAFLD (41% vs. 19%) and insulin resistance (63% vs. 35.5%)
      than a control group. CONCLUSIONS: NAFLD is frequent in patients with PCOS
      confirming a relevant clinical association between these two conditions. Women
      with PCOS should be screened for liver disease.

PMID- 17560683
TI  - Routine screening by brain magnetic resonance imaging decreased the brain
      metastasis rate following surgery for lung adenocarcinoma.
AB  - Since May 1999, the institutional guidelines of Samsung Medical Center, Seoul,
      Korea, have required preoperative magnetic resonance (MR) screening of the brain
      in all patients with lung adenocarcinoma. To investigate the brain metastasis and
      survival rates since the adoption of this guideline, we retrospectively reviewed
      the medical records of patients who underwent complete lung resection between
      January 1995 and December 2000. Recurrence rate, recurrence site, and survival
      were investigated and compared between patients with lung adenocarcinoma who
      underwent complete resection before May 1999, who did not undergo MR screening of
      the brain (non-MR group, n=160), and those after May 1999, who did receive MR
      screening of the brain (MR group, n=86). The brain metastasis rate was lower in
      the MR group than in the non-MR group (p<0.05), especially for the first 2 years.
      However, the recurrence rate at sites other than the brain was similar between
      the two groups. The 5-year survival was higher in the MR group (59%) than in the
      non-MR group (45%, p<0.05). Even in patients with stage I cancer, brain
      metastasis was diagnosed more frequently in the non-MR group (5%) than in the MR
      group (2%). Preoperative MR screening of the brain can help early detection of
      brain metastases in the patients with lung adenocarcinoma prior to surgical
      resection and lead to increase postoperative survival in patients with operable
      lung adenocarcinoma.

PMID- 17560684
TI  - Different dermoscopic faces of dermatofibromas.
AB  - BACKGROUND: Central white scarlike patch and a delicate pigment network at the
      periphery is the typical appearance of dermatofibromas on dermoscopy. OBJECTIVE:
      We aimed to analyze the different dermoscopic appearances of dermatofibromas.
      METHODS: Fifty-two dermatofibromas with dermoscopic features different from the
      classic type, which were detected between May 2003 and July 2005, were evaluated.
      RESULTS: Globules in the scarlike area (38.5%), linear/irregular crypts (26.9%),
      lentigo-like reticular pigmentation (23%), homogeneous blue-gray pigmentation
      (5.9%), and erythematous homogeneous area surrounding the white patch (3.8%) were
      the patterns observed. In addition, dermoscopic features of an atrophic variant
      of dermatofibroma are described, which was seen in one lesion (1.9%).
      LIMITATIONS: None. CONCLUSION: Dermatofibromas have various dermoscopic features.
      Among them, "linear, irregular crypts" is not unusual and is described in this
      study. Homogeneous bluish pigmentation on dermoscopy may be a possible clue for
      the diagnosis of hemosiderotic variants of dermatofibromas.

PMID- 17560685
TI  - Cutaneous responses to vaccinia in individuals with previous smallpox
      vaccination.
AB  - The durability of immune responses to smallpox vaccine is a subject of
      considerable debate. We compared cutaneous vaccinia responses in patients
      vaccinated in the distant past with vaccine-naive individuals using serial close
      up photographs. The previously vaccinated group had a significantly reduced time
      course and milder cutaneous reactions. Vaccinated individuals appear to maintain
      clinically detectable immunity against vaccinia for at least 20 years after
      smallpox vaccination.

PMID- 17560686
TI  - Characterization of the interaction between fenamates and hippocampal neuron
      GABA(A) receptors.
AB  - Fenamate NSAIDs have several central effects, including anti-epileptic and
      neuroprotective actions. The underlying mechanism(s) of these actions are not
      presently understood. In this study, the effects of five members of the fenamate
      NSAID group were investigated on native ligand-gated ion channels expressed in
      cultured rat hippocampal neurons. All fenamates tested (1-100 microM) dose
      dependently potentiated GABA-evoked currents; mefenamic acid (MFA) was the most
      potent and efficacious and was found to shift the GABA dose-response curve to the
      left without effect on the maximum amplitude or the GABA Hill Slope. The
      modulation of GABA receptors by MFA was not reduced in the presence of the
      benzodiazepine antagonist, flumazenil (10 microM) and was moderately voltage
      dependent. MFA at concentrations >or=10 microM evoked dose-dependent currents in
      the absence of GABA. These currents were potentiated by diazepam (1 microM) and
      blocked by bicuculline (10 microM). The MFA (50 microM) current-voltage
      relationship and reversal potential were similar to that evoked by GABA. MFA (1
      100 microM) had no effects on sub-maximal glycine, glutamate or NMDA evoked
      currents. These data show that fenamate NSAIDs are a highly effective class of
      GABA(A) receptor modulator and activators.

PMID- 17560687
TI  - Tauopathy in human and experimental variant Creutzfeldt-Jakob disease.
AB  - Cerebral accumulation of hyperphosphorylated tau (phospho-tau) occurs in several
      neurodegenerative conditions including Alzheimer disease. In prion diseases,
      phospho-tau deposition has been described in a rare genetic form, Gerstmann
      Straussler-Scheinker disease, but is not considered part of the neuropathological
      picture of Creutzfeldt-Jakob disease. Aim of this study was to investigate
      whether changes related to phospho-tau accumulation are present in the brain of
      patients with variant Creutzfeldt-Jakob disease (vCJD) that shares with Gerstmann
      Straussler-Scheinker disease abundant prion protein (PrP) deposition in amyloid
      form. The analysis was extended to experimental mouse models of vCJD. We detected
      a large number of phospho-tau-immunoreactive neuritic profiles, often clustered
      around PrP amyloid deposits, not only in the cerebral cortex, but also in the
      cerebellum of all vCJD patients examined, in the absence of Abeta. Although less
      constantly, phospho-tau was localized in some perikaria and dendrites. The
      biochemical counterpart was the presence of phospho-tau in the detergent
      insoluble fraction of cerebral cortex. Phospho-tau-immunoreactive neuronal
      profiles were also found in association with PrP deposits in mouse models of
      vCJD. These findings suggest that the abnormal forms of PrP associated with vCJD
      trigger a tauopathy, and provide a paradigm for the early stages of tau pathology
      associated with cerebral amyloidoses, including Alzheimer disease.

PMID- 17560688
TI  - Neuroglobin protects PC12 cells against beta-amyloid-induced cell injury.
AB  - Excessive accumulation of amyloid beta (Abeta) has been proposed as a pivotal
      event in the pathogenesis of Alzheimer's disease. Possible mechanisms underlying
      Abeta-induced neuronal cytotoxicity include excess production of reactive
      oxidative species (ROS) and apoptosis. Neuroglobin (Ngb), a newly discovered
      globin in vertebrates that exhibits neuroprotective functions, may have a
      potential role in scavenging ROS. To examine the potential protective role of Ngb
      in Abeta-induced cytotoxicity, PC12 cells were treated with Abeta (1-42 fragment)
      for 24h. Abeta treatments increased ROS production in PC12 cells. Overexpression
      of Ngb but not Ngb mutant in the PC12 cells significantly attenuated Abeta
      induced ROS production and lipids peroxidation. Furthermore, overexpression of
      Ngb also attenuated Abeta-induced mitochondrial dysfunction and apoptosis, and
      promoted cell survival in PC12 cells. Therefore, Ngb may act as an intracellular
      ROS scavenger, and such antioxidant properties may play a protective role against
      Abeta-induced cell injury.

PMID- 17560689
TI  - Functional connectivity of the hippocampus in elderly with mild memory
      dysfunction carrying the APOE epsilon4 allele.
AB  - The purpose of the present study was to evaluate functional connectivity of the
      hippocampus during a fMRI face-name learning task in a group of elders with mild
      memory impairment on the basis of the presence or absence of the APOE epsilon4
      allele. Twelve epsilon4 carriers and 20 non-carriers with mild memory dysfunction
      and exhibiting equivalent performance in clinical evaluations of global cognitive
      function and memory were studied. Subjects underwent a fMRI session consisting of
      a face-name encoding memory task. Following scanning, subjects were asked to pair
      faces with their corresponding proper name. Functional connectivity of the
      hippocampus was measured by using coherence analysis to evaluate the activity of
      brain circuits related to memory encoding processes. In contrast to non-APOE
      epsilon4 allele bearers, APOE epsilon4 carriers showed enhanced connectivity with
      the anterior cingulate, inferior parietal/postcentral gyrus region and the
      caudate nucleus. Enhanced hippocampal connectivity with additional brain regions
      in APOE epsilon4 allele carriers during the performance of an associative memory
      task may reveal the existence of additional activity in the cortico-subcortical
      network engaged during memory encoding in subjects carrying this genetic variant.

PMID- 17560690
TI  - Aging elevates metabolic gene expression in brain cholinergic neurons.
AB  - The basal forebrain (BF) cholinergic system is selectively vulnerable in human
      brain diseases, while the cholinergic groups in the upper pons of the brainstem
      (BS) resist neurodegeneration. Cholinergic neurons (200 per region per animal)
      were laser-microdissected from five young (8 months) and five aged (24 months)
      F344 rats from the BF and the BS pontine lateral dorsal
      tegmental/pedunculopontine nuclei (LDTN/PPN) and their expression profiles were
      obtained. The bioinformatics program SigPathway was used to identify gene groups
      and pathways that were selectively affected by aging. In the BF cholinergic
      system, aging most significantly altered genes involved with a variety of
      metabolic functions. In contrast, BS cholinergic neuronal age effects included
      gene groupings related to neuronal plasticity and a broad range of normal
      cellular functions. Transcription factor GA-binding protein alpha (GABPalpha),
      which controls expression of nuclear genes encoding mitochondrial proteins, was
      more strongly upregulated in the BF cholinergic neurons (+107%) than in the BS
      cholinergic population (+40%). The results suggest that aging elicits elevates
      metabolic activity in cholinergic populations and that this occurs to a much
      greater degree in the BF group than in the BS group.

PMID- 17560691
TI  - Regional specificity of age effects on the neural correlates of episodic
      retrieval.
AB  - We investigated age-related differences in episodic retrieval using a source
      memory procedure. Age-related differences in retrieval-related activity were
      analyzed in conditions where source recollection performance was statistically
      equivalent in young and older subjects. Analyses of BOLD activity revealed a
      network of regions where recollection effects were equivalent in magnitude in the
      two age groups. There were no regions where these effects were of greater
      magnitude in young than in older subjects. In some regions, however, there was a
      crossover interaction, such that retrieval-related effects reversed in direction
      between the two age groups. Further analyses of these interactions revealed a
      dissociation between a posterior hippocampal region where recollection-related
      activity was confined to the older group, and right fusiform and occipital
      regions where, in the young group only, activity elicited by studied items was of
      lower magnitude than activity to new items. We interpret the first of these age
      related effects as an example of 'over-recruitment' in response to decline in
      neural efficiency, and discuss whether the second effect indexes an age-related
      decline in repetition priming.

PMID- 17560692
TI  - Enteric fever due to Salmonella typhi and paratyphi A a neglected and emerging
      problem.

PMID- 17560693
TI  - Guillain-Barre syndrome after vaccination in United States a report from the
      CDC/FDA Vaccine Adverse Event Reporting System.
AB  - Using the data from Vaccine Adverse Event Reporting System, we present 54 reports
      of Guillain-Barre Syndrome (GBS) after vaccination that occurred in United States
      in 2004. In 38 of the patients, GBS occurred within 6 weeks. The highest number
      (n=31) of GBS was observed in patients receiving influenza vaccine followed by
      hepatitis vaccine (n=9), 1 patient died and 10 patients were disabled following
      the event. We conclude that vaccines other than influenza vaccine can be
      associated with GBS.

PMID- 17560694
TI  - Efficacy of a live attenuated tetravalent candidate dengue vaccine in naive and
      previously infected cynomolgus macaques.
AB  - The development of a safe and effective vaccine against dengue is a public health
      priority. Attempts to evaluate candidate vaccine formulations in human volunteers
      were largely unsuccessful, at least in part due to too high reactogenicity of
      some of the candidate vaccines tested. We evaluated a live attenuated tetravalent
      dengue vaccine candidate in flavivirus naive and dengue virus type 3 immune non
      human primates. Immune responses were measured both at the humoral and the
      cellular level and the efficacy of this vaccine candidate was evaluated by
      challenging the vaccinated animals with dengue virus type 4. Humoral and cellular
      immune responses upon vaccination were similar to those described after natural
      infection in humans. All animals were protected from developing viremia upon
      challenge infection. In addition, primary dengue virus type 3 infection of
      macaques neither influenced the immune response upon vaccination, nor interfered
      with vaccine-induced protection from dengue virus type 4 challenge infection. The
      data suggest that the live attenuated tetravalent vaccine candidate used is
      promising and warrant further safety and efficacy testing in clinical trials.

PMID- 17560695
TI  - Vaccinating adolescents against meningococcal disease in Canada: a cost
      effectiveness analysis.
AB  - BACKGROUND: One dose of serogroup C meningococcal conjugate vaccine (MCV-C) at 12
      months of age is the most common immunization schedule in Canada, but immunity
      may wane over time. OBJECTIVES: To assess the cost-effectiveness of a booster
      dose at 12 years of age with either MCV-C or a quadrivalent ACYW135 meningococcal
      conjugate vaccine (MCV-4). METHODS: A simulation model for assessing both the
      direct and indirect effects of vaccination was developed. Age- and serogroup
      specific incidence and fatality rates were derived from Canadian surveillance
      data. Vaccine efficacy was estimated from data from the U.K. and Spain, assuming
      an age-dependent decline of vaccine efficacy over time. Expected vaccine coverage
      rates were 90% at 12 months, and 70% at 12 years. Herd immunity was modeled using
      UK data. Vaccine purchase price per dose was $23 for MCV-C and $70 for MCV-4.
      Costs and health outcomes were discounted at 3% per year. Results, expressed in
      2004 Canadian $ and from a societal perspective, were presented for a steady
      state situation and a population of 1 million. RESULTS: Under the "no
      vaccination" base scenario, 5.7 cases of vaccine-preventable meningococcal
      disease would occur each year. Vaccination at 12 months using MCV-C would reduce
      the burden of disease by 32%. Adding MCV-C at 12 years of age would reduce the
      number of cases by 55% at no marginal cost, while using MCV-4 would result in a
      disease reduction of 78% for a marginal cost of $31000 per QALY gained. Comparing
      MCV-4 with MCV-C as a booster dose, the incremental cost-effectiveness ratio
      would be $113000 per QALY. The efficacy of C-MCV vaccination at 12 months and the
      differential price between the two vaccines were the parameters having the
      strongest impact on the cost/QALY ratios. Any increase in the incidence of
      serogroup Y will improve the marginal cost-effectiveness ratio associated with
      MCV-4. CONCLUSION: Adolescent revaccination would be beneficial. Using C-MCV
      would be the most cost-effective option, while using MCV-4 would be more
      effective but would also require more investment.

PMID- 17560696
TI  - Septic arthritis of the temporomandibular joint in a 6-year-old child.
AB  - Septic arthritis of the temporomandibular joint (TMJ) is rare, and is almost
      exclusively confined to adults; we know of only four cases previously described
      in children. We present a 6-year-old girl who had septic arthritis of the
      temporomandibular joint with no obvious cause. We stress the need for prompt
      diagnosis and intervention to prevent serious consequences.

PMID- 17560697
TI  - Endoscopically-guided core biopsy of the condylar head.
AB  - The effective management of mandibular cysts and tumours relies on obtaining an
      accurate tissue diagnosis with the acquisition of specimens representative of the
      lining and/or contents of the lesion. Access to such abnormalities is not
      commonly an issue since bony windows can be made in readily accessible areas.
      However, less accessible regions such as the ascending ramus, coronoid process
      and condyle can be surgically challenging without an extensive lateral approach.
      This paper reports a minimally-invasive technique in which an endoscope was used
      to facilitate the core biopsy of a condylar lesion.

PMID- 17560698
TI  - The effect of axis alignment on shoulder joint kinematics analysis during arm
      abduction.
AB  - BACKGROUND: A joint coordinate system allows coherence between the performed
      movement, its mathematical representation and the clinical interpretation of the
      kinematics of joint motion. In 2005, the International Society of Biomechanics
      (ISB) defined a joint coordinate system for the shoulder. To improve kinematics
      interpretation, the ISB suggested aligning the coordinate systems of the humerus
      and the scapula. Therefore, the aim of this research project was to determine how
      the alignment of the joint coordinate system axes can influence the
      interpretation of shoulder joint kinematics. More precisely, we wanted to
      investigate if mathematical alignment of the reference and moving coordinate
      system axes could facilitate the kinematic interpretation of a simple abduction
      movement without introducing additional coupled motion. METHODS: An experiment
      was carried out on eight shoulder cadaveric specimens. Elevation of the arm in
      the scapular plane (abduction) was recorded using an electromagnetic tracking
      device. Three-dimensional angular displacements of the arm during elevation in
      the scapular plane were described using the standard ISB joint coordinate system,
      and using a modified joint coordinate system for which the axes were
      mathematically aligned. FINDINGS: The results obtained revealed a difference in
      the interpretation of the starting angles between the ISB joint coordinate system
      and the aligned coordinate system. No difference was found in the interpretation
      of the angular range of motion (P<0.01). INTERPRETATION: The aligned coordinate
      system provided a standardized starting angle of elevation that allows an easier
      clinical interpretation of shoulder kinematics.

PMID- 17560699
TI  - In vivo measurement of subacromial space width during shoulder elevation:
      technique and preliminary results in patients following unilateral rotator cuff
      repair.
AB  - BACKGROUND: The shoulder's subacromial space is of significant clinical interest
      due to its association with rotator cuff disease. Previous studies have estimated
      the subacromial space width to be 2-17 mm, but no study has measured in vivo
      subacromial space width during shoulder motion. The purpose of this study was to
      measure the in vivo subacromial space width during shoulder elevation in patients
      following rotator cuff repair. METHODS: Biplane X-ray images were collected
      during shoulder elevation of 11 patients who had undergone rotator cuff repair.
      Glenohumeral joint motion was measured from the biplane X-ray images for each
      subject's repaired and asymptomatic, contralateral shoulders. The joint motion
      data were combined with subject-specific CT models to measure the subacromial
      space width during shoulder motion. FINDINGS: Subacromial space width decreased
      with shoulder elevation, ranging from 2.3 to 7.4 mm in the repaired shoulder and
      1.2-7.1 mm in the contralateral shoulder. Subacromial space width in the repaired
      shoulder was only 0.5 mm less than the contralateral shoulder when averaged over
      10-60 degrees of glenohumeral elevation. INTERPRETATION: The results indicate
      that the humerus in the repaired shoulder is positioned more cranially on the
      glenoid than in the contralateral shoulder. It is unclear if these subtle
      differences in subacromial space width are due to the surgical procedure or post
      operative stiffness, or if subacromial impingement contributed to the development
      of the rotator cuff tear. Future research will ascertain if these results
      represent a transient response to the surgery or a more fundamental difference in
      rotator cuff function between repaired and contralateral shoulders.

PMID- 17560700
TI  - DDT uptake by arbuscular mycorrhizal alfalfa and depletion in soil as influenced
      by soil application of a non-ionic surfactant.
AB  - A greenhouse pot experiment was conducted to investigate the colonization of
      alfalfa roots by the arbuscular mycorrhizal (AM) fungus Glomus etunicatum and
      application of the non-ionic surfactant Triton X-100 on DDT uptake by alfalfa and
      depletion in soil. Mycorrhizal colonization led to an increase in the
      accumulation of DDT in roots but a decrease in shoots. The combination of AM
      inoculation and Triton X-100 application enhanced DDT uptake by both the roots
      and shoots. Application of Triton X-100 gave much lower residual concentrations
      of DDT in the bulk soil than in the rhizosphere soil or in the bulk soil without
      Triton X-100. AM colonization significantly increased bacterial and fungal counts
      and dehydrogenase activity in the rhizosphere soil. The combined AM inoculation
      of plants and soil application of surfactant may have potential as a
      biotechnological approach for the decontamination of soil polluted with DDT.

PMID- 17560701
TI  - Skin contact transfer of three fragrance residues from candles to human hands.
AB  - The dermal hand transfer of three fragrance materials (cinnamic aldehyde, d
      limonene and eugenol) from scented candles was determined in 10 subjects (i.e.,
      20 hands) after grasping scented candles for 5 consecutive 20s exposures/grasps.
      The fragrance materials from each subject's hands were recovered by isopropyl
      alcohol wipes and subsequent extractions. Removal efficiencies for both cinnamic
      aldehyde and eugenol placed directly on the hands were not concentration
      dependent and ranged from 103% to 106%. The removal efficiency of d-limonene
      showed an inverse relation with 74.3% removed at the low concentration of 50
      microg and 63.8% removed at the high concentration of 500 microg. The
      residue/transfer of d-limonene from the candles to the hands was below the limit
      of detection of 50 microg. The residue/transfer of cinnamic aldehyde and eugenol
      to each subject's hands was consistent between subjects as well as between each
      exposure/grasp. The total mean residues of cinnamic aldehyde and eugenol
      transferred per grasp from the candles to the hands were 0.255 microg/cm(2) and
      0.279 microg/cm(2), respectively.

PMID- 17560702
TI  - Transactional sex with casual and main partners among young South African men in
      the rural Eastern Cape: prevalence, predictors, and associations with gender
      based violence.
AB  - We explored the prevalence and predictors of transactional sex with casual
      partners and main girlfriends among 1288 men aged 15-26 from 70 villages in the
      rural Eastern Cape province of South Africa. Data were collected through face-to
      face interviews with young men enroling in the Stepping Stones HIV prevention
      trial. A total of 17.7% of participants reported giving material resources or
      money to casual sex partners and 6.6% received resources from a casual partner.
      Transactionally motivated relationships with main girlfriends were more balanced
      between giving (14.9%) and getting (14.3%). We constructed multivariable models
      to identify the predictors for giving and for getting material resources in
      casual and in main relationships. Each model resulted in remarkably similar
      predictors. All four types of exchange were associated with higher socio-economic
      status, more adverse childhood experiences, more lifetime sexual partners, and
      alcohol use. Men who were more resistant to peer pressure to have sex were less
      likely to report transactional sex with casual partners, and men who reported
      more equitable gender attitudes were less likely to report main partnerships
      underpinned by exchange. The most consistent predictors of all four types of
      transaction were perpetration of intimate partner violence and rape against women
      other than a main partner. The strong and consistent association between
      perpetration of gender-based violence and both giving and getting material goods
      from female partners suggests that transactional sex in both main and casual
      relationships should be viewed within a broader continuum of men's exercise of
      gendered power and control. HIV prevention interventions need to explicitly
      address transactional sex in the context of ideas about masculinity, which place
      a high emphasis on heterosexual success with, and control of, women.

PMID- 17560703
TI  - Guardianship of people with mental disorders.
AB  - The duty of a guardian is to protect a patient who is unable to care for himself
      or herself. Guardianship has been considered an abrogation of autonomy while
      conversely it often prevents irreversible harm to the patient. We examined the
      decision-making process for appointing a guardian in 60 cases from one mental
      health center in Israel, by examining the patients' medical records and court
      appeals. The results of our study suggest that guardians are usually appointed
      only in extreme cases, though alternative solutions are rarely sought, and that
      clear criteria for physicians when recommending guardianship are lacking.

PMID- 17560704
TI  - Safety evaluation of a standardized phytochemical composition extracted from
      Bacopa monnieri in Sprague--Dawley rats.
AB  - BacoMind is an enriched phytochemical composition derived from Bacopa monnieri, a
      common medicinal plant having multiple uses in the traditional system of medicine
      and particularly used as a memory enhancing agent for centuries. The plant and
      its extracts have been evaluated for anti-inflammatory, cardio tonic, sedative
      and neuro-muscular blocking activities. In view of the extensive use of this
      plant, BacoMind , standardized to bioactive compounds was evaluated in a series
      of toxicity studies, to confirm the safety of its usage. BacoMind , on single
      oral administration had a median lethal dose of 2,400 mg/kg in Sprague-Dawley
      rats. In a 14 day repeated dose oral toxicity study in rats, except for mild
      lowering in body weight gain in male rats, it was found to be tolerated well up
      to the dose of 500 mg/kg. A subchronic oral toxicity study for 90 days in rats at
      the dose levels of 85, 210 and 500 mg/kg did not reveal any evidence of toxicity
      with respect to clinical signs, neurological examination, food consumption, body
      weight gain, haematological and blood biochemistry parameters. The absolute and
      relative organ weight of vital organs did not differ significantly from that of
      the control. Necropsy and histopathological examination, did not reveal any
      remarkable and treatment related changes. A no-observed adverse effect level of
      500 mg/kg body weight was established in rats.

PMID- 17560705
TI  - Induction of the cholesterol biosynthesis pathway in differentiated Caco-2 cells
      by the potato glycoalkaloid alpha-chaconine.
AB  - Glycoalkaloids are naturally occurring toxins in potatoes, which at high levels
      may induce toxic effects in humans, mainly on the gastrointestinal tract by cell
      membrane disruption. In order to better understand the molecular mechanisms
      underlying glycoalkaloid toxicity, we examined the effects of alpha-chaconine on
      gene expression in the Caco-2 intestinal epithelial cell line using DNA
      microarrays. Caco-2 cells were exposed for 6h to 10 microM alpha-chaconine in
      three independent experiments (randomized block design). The most prominent
      finding from our gene expression and pathway analyses was the upregulation of
      expression of several genes involved in cholesterol biosynthesis. This to some
      extent is in line with the literature-described mechanism of cell membrane
      disruption by glycoalkaloids. In addition, various growth factor signaling
      pathways were found to be significantly upregulated. This study is useful in
      understanding the mechanism(s) of alpha-chaconine toxicity, which may be extended
      to other potato glycoalkaloids more generally.

PMID- 17560706
TI  - Effects of various plant polyphenols on bladder carcinogen benzidine-induced
      mutagenicity.
AB  - Benzidine (Bz), a human bladder carcinogen, was strongly mutagenic to Salmonella
      TA102 tester strain in the Ames Salmonella microsome/mutagenicity assay in the
      presence of rat liver S9 mix. Various non-mutagenic plant polyphenols were
      included in the assay to test their inhibitory effects on the Bz-induced
      mutations. Coumestrol, ellagic acid (EA), (-)-epicatechin (EC), (-)
      epichatechingallate (ECG), gallic acid (GA), (-)-gallocatechin (GC), plumbagin,
      propyl gallate (PG), taxifolin, and 2,2',4'-trihydroxychalcone were found to have
      a strong inhibitory effect on Bz-induced mutations. (-)-Epigallo-catechingallate
      (EGCG), fisetin, (-)-gallocatechingallate (GCG), and piceatannol were moderately
      inhibitory to the mutations; whereas, (-)-catechin, (-)-catechingallate (CG), and
      reseveratrol were weakly inhibitory to the mutations. (-)-Epigallocatechin (EGC)
      and 7,3',4'-trihydroxy isoflavon were not inhibitory to the Bz-induced mutations.
      Isoliquirtigenin, quercetin dihydrate, and rhein were found to be mutagenic in
      tester strain TA102. Benzidine mediated lipid peroxidation was conducted
      employing the thiobarbituric acid reactive substances (TBARS) assay using
      linoleic acid as a substrate. In the presence of rat liver S9 mix, Bz could cause
      lipid peroxidation as an outcome of production of oxygen free radicals.
      Incorporation of the above mentioned non-mutagenic plant polyphenols
      significantly inhibited benzidine mediated lipid peroxidation in a time dependent
      manner. These polyphenols also effectively reduced the iron mediated lipid
      peroxidation. Thus, it is concluded that the inhibition of oxidative mutagenicity
      of Bz by plant polyphenols could be due to an inhibitory effect of plant
      polyphenols on the bioactivating enzymes such as cytochrome P-450 and peroxidase
      and the chelation of iron present in the cytochrome P-450 in the S9 mix. Thus,
      these plant polyphenols play a significant inhibitory role on Bz-induced
      mutagenicity.

PMID- 17560707
TI  - Differential expression of chicken hepatic genes responsive to PFOA and PFOS.
AB  - The effects of PFOS and PFOA on the gene expression patterns of chickens that
      were exposed to either PFOS or PFOA at low doses were investigated with the use
      of microarray techniques. Twelve Genechip Chicken Genome Arrays were used to
      study hepatic gene expression in 6-week-old chickens (Gallus gallus) that were
      exposed to either PFOA (0.1, 0.5, or 5mg/mL), PFOS (0.02 or 0.1mg/mL), or a
      saline vehicle control (0.9% NaCl in Milli-Q water) via subcutaneous implantation
      of a 2mL osmotic pump for 4 weeks or for 4 weeks with a further 4 weeks of
      depuration. Over 240 and 480 genes were significantly affected by PFOS after 4
      weeks of exposure and after 4 weeks of exposure with a further 4 weeks of
      depuration, respectively and over 290 and 320 genes were significantly affected
      by PFOA, correspondingly. For PFOS, the genes that were affected after 4 weeks of
      exposure were mainly related to the transport of electrons and oxygen, and the
      metabolism of lipids and fatty acids; while the genes that were affected after 4
      weeks of exposure with a further 4 weeks of depuration were mainly related to the
      transport of electrons and ions, and protein amino acid phosphorylation and
      proteolysis. For PFOA, the genes that were affected after 4 weeks of exposure
      were related to the transport of ions, lipids, and electrons and cytochromes;
      while the genes that were affected after 4 weeks of exposure with a further 4
      weeks of depuration were related to protein amino acid phosphorylation and
      proteolysis, the transport of ions, and the metabolism of fatty acids and lipids.
      The results also showed that the gene expression patterns between chickens that
      were treated with PFOS and those that were treated with PFOA were different,
      which points to the importance of the separate evaluation of the toxicities of
      PFOS and PFOA. Specifically, the gene expressions of CYP8B and NOV were studied.

PMID- 17560708
TI  - Fallopian tube torsion and hematolsalpinx in a menopausal woman.

PMID- 17560709
TI  - A model for triple helix formation on human telomerase reverse transcriptase
      (hTERT) promoter and stabilization by specific interactions with the water
      soluble perylene derivative, DAPER.
AB  - The promoter of human telomerase reverse transcriptase (hTERT) gene, in the
      region from -1000 to +1, contains two homopurine-homopyrimidine sequences (-835/
      814 and -108/-90), that can be considered as potential targets to triple helix
      forming oligonucleotides (TFOs) for applying antigene strategy. We have chosen
      the sequence (-108/-90) on the basis of its unfavorable chromatin organization,
      evaluated by theoretical nucleosome positioning and nuclease hypersensitive sites
      mapping. On this sequence, anti-parallel triplex with satisfactory thermodynamic
      stability is formed by two TFOs, having different lengths. Triplex stability is
      significantly increased by specific interactions with the perylene derivative
      N,N'-bis[3,3'-(dimethylamino) propylamine]-3,4,9,10-perylenetetracarboxylic
      diimide (DAPER). Since DAPER is a symmetric molecule, the induced Circular
      Dichroism (CD) spectra in the range 400-600 nm allows us to obtain information on
      drug binding to triplex and duplex DNA. The drug-induced ellipticity is
      significantly higher in the case of triplex with respect to duplex and,
      surprisingly, it increases at decreasing of DNA. A model is proposed where self
      stacked DAPER binds to triplex or to duplex narrow grooves.

PMID- 17560710
TI  - Thermochemical esterifying citric acid onto lignocellulose for enhancing
      methylene blue sorption capacity of rice straw.
AB  - In this paper, rice straw was esterified thermochemically with citric acid (CA)
      to produce potentially biodegradable cationic sorbent. The modified rice straw
      (MRS) and crude rice straw (CRS) were evaluated for their methylene blue (MB)
      removal capacity from aqueous solution. The effects of various experimental
      parameters (e.g., initial pH, sorbent dose, dye concentration, ion strength, and
      contact time) were examined. The ratio of MB sorbed on CRS increased as the
      initial pH was increased from pH 2 to 10. For MRS, the MB removal ratio came up
      to the maximum value beyond pH 3. The 1.5 g/l or up of MRS could almost
      completely remove the dye from 250 mg/l of MB solution. The ratio of MB sorbed
      kept above 98% over a range from 50 to 450 mg/l of MB concentration when 2.0 g/l
      of MRS was used. Increase in ion strength of solution induced decline of MB
      sorption. The isothermal data fitted the Langmuir model. The sorption processes
      followed the pseudo-first-order rate kinetics. The intraparticle diffusion rate
      constant (k(id)) was greatly increased due to modification.

PMID- 17560711
TI  - Re: Salvatore Siracusano, Francesca Vita, Rita Abbate, Stefano Ciciliato,
      Violetta Borelli, Massimiliano Bernabei and Giuliano Zabucchi. The role of
      granulocytes following intravesical BCG prophylaxis. Eur Urol 2007;51:1589-99.

PMID- 17560712
TI  - Distribution of polycyclic aromatic hydrocarbons in water, sediment and soil in
      drinking water resource of Zhejiang Province, China.
AB  - The spatial and temporal distribution of polycyclic aromatic hydrocarbons (PAHs)
      was investigated in Qiantang River, the most important drinking water resource in
      Zhejiang Province, China. A total of 270 water samples, 64 sediment samples and
      21 soil samples near riverbank were collected during January 2005-July 2006. The
      total concentrations of PAHs in water, sediments and soils ranged from 70.3 to
      1844.4 ng/L, from 91.3 to 1835.2 ng/g and from 85.2 to 676.2 ng/g, respectively.
      The concentrations of PAHs in rural areas were lower than those in city zones.
      The concentrations of PAHs in July were the lowest while those in January were
      the highest during four seasons. The concentrations of PAHs in 2006 were compared
      with those in 2003 and 2005. The result showed PAHs pollution in this drinking
      water resource was increasing with time. The relationship between log K(oc) and
      log K(ow) of PAHs for field data on sediments and predicted values indicated that
      Qiantang River was mainly contaminated by petrogenic PAHs. The same result was
      obtained by the ratios of AN/(AN + Phen) and Flur/(Flur + Pye). Ratios of K(oc)
      for PAHs on sediments to that on corresponding soils indicated that PAHs in
      Qiantang River were mainly obtained from soil runoff.

PMID- 17560713
TI  - Seasonal variations of chemical and physical characteristics of dissolved organic
      matter and trihalomethane precursors in a reservoir: a case study.
AB  - Dissolved organic matter (DOM) and its potential to form disinfection by-products
      (DBPs) during water treatment are of great public health concern. Understanding
      the seasonal changes in DOM composition and their reactivity in DBP formation
      could lead to a better treatment of drinking water and a more consistent water
      quality. DOM from the East-Lake, a reservoir in the south-China, was fractionated
      and characterized by XAD resin adsorption (RA) and ultrafiltration (UF)
      techniques during different seasons within a year. The properties of chemical
      fractions (isolated by RA) appeared more stable than those of physical fractions
      (separated by UF) throughout the sampling period. The relative contribution of
      each chemical fraction to the total dissolved organic carbon (DOC), UV(254)
      absorbance and trihalomethane formation potential (THMFP) remained relatively
      constant across the sampling period. However, the physical (molecular weight)
      fractions of the DOM exhibited large seasonal changes in UV(254) and THMFP.
      Compared to the parameter of DOC, the THMFP and specific THMFP (STHMFP) of either
      chemical or physical fractions were more variable. In terms of DOC concentration,
      the hydrophobic acids (HoA) and hydrophilic matter (HiM) dominated in the DOM in
      most of the seasons; while the components with molecular weight of 10-30 kDa and
      less than 1 kDa were the predominant physical fractions.

PMID- 17560714
TI  - Sonochemical synthesis and photocatalytic activity of meso- and macro-porous
      TiO(2) for oxidation of toluene.
AB  - Meso-and macro-porous TiO(2) were synthesized by ultrasonic induced solvothermal
      method. Octadecylamine as a soft template was used to direct the formation of
      porous structure. The as-prepared porous TiO(2) was characterized by low angle
      and wide angle X-ray diffraction, N(2) adsorption-desorption isotherms and BET
      surface area. The energy influence of ultrasound and heat and concentration of
      nitric acid for post extraction on formation of porous structure were
      investigated. The photocatalytic activities of TiO(2) were investigated by
      degrading toluene gas under UV light. The results revealed that proper energy
      facilitates the formation of porous structure and too low concentration of nitric
      acid cannot extract template from pores. The photocatalytic activities of TiO(2)
      with porous structure are higher than those of nonporous ones.

PMID- 17560715
TI  - Safe disposal of toxic chrome buffing dust generated from leather industries.
AB  - The high concentration of trivalent chromium along with organic/inorganic
      compounds in chrome buffing dust (CBD), the solid waste discharged from leather
      industries, causes severe groundwater contamination on land co-disposal and
      chronic air pollution during thermal incineration. In the present investigation,
      CBD was subjected to starved air incineration (SAI) at 800 degrees C in a thermal
      incinerator under different flow rates of oxygen to optimize the oxygen required
      to incinerate the organic compounds and simultaneously preventing the conversion
      of Cr(3+) to Cr(6+). The energy audit of SAI of buffing dust under the external
      supply of oxygen was carried out under different incineration conditions. The
      bottom ash from SAI was effectively solidified/stabilized using Portland cement
      and fine aggregate. The solidified blocks were tested for unconfined compressive
      strength and heavy metal leaching. Unconfined compressive strength of the blocks
      was in the range of 120-180 kg/cm(2). The stabilization of chromium(III) in the
      cement gel matrix was confirmed using Scanning Electron Microscopy SEM, Electron
      Paramagnetic Resonance spectroscopy (EPR) and X-ray diffraction spectroscopy
      (XRD). Leachability studies through TCLP on solidified blocks were carried out to
      determine the degree of leaching of chromium and organic compounds (expressed as
      COD) under standard conditions.

PMID- 17560716
TI  - Comparison and evaluation of methods for the determination of flammability
      limits, applied to methane/hydrogen/air mixtures.
AB  - Different methods, both experimental and numerical, to determine the flammability
      limits are compared and evaluated, exemplified by a determination of the
      flammability limits of methane/hydrogen/air mixtures for hydrogen fuel molar
      fractions of 0, 0.2, 0.4 and 0.6, at atmospheric pressure and ambient
      temperature. Two different experimental methods are used. The first method uses a
      glass tube with visual observation of the flame, whereas the second method uses a
      closed spherical vessel with a pressure rise criterion to determine whether flame
      propagation has occurred. In addition to these experiments, the flammability
      limits are determined numerically. Unsteady planar and spherically expanding
      flames are calculated with a one-dimensional flame code with the inclusion of
      radiation heat loss in the optically thin limit. Comparison of the experimental
      results with the results of the planar flame calculations shows large
      differences, especially for lean mixtures. These differences increase with
      increasing hydrogen content in the fuel. Better agreement with the experimental
      results is found for the spherically expanding flame calculations. A limiting
      burning velocity of 5 cm/s is found to predict the upper flammability limit
      determined with the tube method very well, whereas the limiting flame temperature
      approach was found to give poorer agreement. Further analysis indicates that the
      neglect of flame front instabilities is the probable cause of the large
      differences between experimental and numerical results at the lower flammability
      limit.

PMID- 17560717
TI  - On-line separation and preconcentration of lead(II) by solid-phase extraction
      using activated carbon loaded with xylenol orange and its determination by flame
      atomic absorption spectrometry.
AB  - Activated carbon loaded with xylenol orange in a mini-column was used for the
      highly selective separation and preconcentration of Pb(II) ions. An on-line
      system for enrichment and the determination of Pb(II) was carried out on flame
      atomic absorption spectrometry. The conditions of preconcentration and
      quantitative recovery of Pb(II) from diluted solution, such as pH of aqueous
      phase, amount of the sorbent, volume of the solutions and flow variables were
      studied as well as effect of potential interfering ions. Under the optimum
      conditions, Pb(II) in an aqueous sample was concentrated about 200-fold and the
      detection limit was 0.4 ng mL(-1) Pb(II). The adsorption capacity of the solid
      phase was 0.20mg of lead per one gram of the modified activated carbon. The
      modified activated carbon is stable for several treatments of sample solutions
      without the need for using any chemical reagent. The recovery of lead(II) from
      river water, waste water, tap water, and in the following reference materials:
      SRM 2711 Montana soil and GBW-07605 tea were obtained in the range of 97-104% by
      the proposed method.

PMID- 17560718
TI  - Rotenone potentiates NMDA currents in substantia nigra dopamine neurons.
AB  - Rotenone is a pesticide that produces a rodent model of Parkinson's disease.
      Although much evidence suggests that oxidative stress mediates the toxicity of
      rotenone on dopamine neurons, rotenone can also potentiate glutamate
      excitotoxicity. We used whole-cell patch pipettes to investigate actions of
      rotenone on currents evoked by N-methyl-d-aspartate (NMDA) in dopamine neurons in
      slices of rat midbrain. After superfusing the slice for 20-30 min, rotenone (100
      nM) caused a 162% increase in the average amplitude of inward current evoked by
      30 microM NMDA. This effect of rotenone was mimicked by the sodium pump inhibitor
      strophanthidin (10 microM) and was abolished when pipettes contained an ATP
      regeneration solution. Although strophanthidin also significantly increased the
      amplitude of inward currents evoked by (+/-)-alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionic acid (AMPA; 10 microM), rotenone failed to potentiate AMPA
      currents. Because rotenone potentiated NMDA- but not AMPA-dependent currents,
      this suggests that rotenone acts selectively to augment NMDA receptor function.
      Furthermore, the failure of rotenone to mimic strophanthidin suggests that
      rotenone does not inhibit sodium pump activity. Our results suggest that an
      excitotoxic mechanism might contribute to rotenone neurotoxicity.

PMID- 17560719
TI  - pain2: A neuropathic pain QTL identified on rat chromosome 2.
AB  - We aimed to locate a chronic pain-associated QTL in the rat (Rattus norvegicus)
      based on previous findings of a QTL (pain1) on chromosome 15 of the mouse (Mus
      musculus). The work was based on rat selection lines HA (high autotomy) and LA
      (low autotomy) which show a contrasting pain phenotype in response to nerve
      injury in the neuroma model of neuropathic pain. An F(2) segregating population
      was generated from HA and LA animals. Phenotyped F(2) rats were genotyped on
      chromosome 7 and chromosome 2, regions that share a partial homology with mouse
      chromosome 15. Our interval mapping analysis revealed a LOD score value of 3.63
      (corresponding to p=0.005 after correcting for multiple testing using
      permutations) on rat chromosome 2, which is suggestive of the presence of a QTL
      affecting the predisposition to neuropathic pain. This QTL was mapped to the 14
      26cM interval of chromosome 2. Interestingly, this region is syntenic to mouse
      chromosome 13, rather than to the region of mouse chromosome 15 that contains
      pain1. This chromosomal position indicates that it is possibly a new QTL, and
      hence we name it pain2. Further work is needed to replicate and to uncover the
      underlying gene(s) in both species.

PMID- 17560720
TI  - Effects of opioid blockade on the modulation of pain and mood by sweet taste and
      blood pressure in young adults.
AB  - Increased blood pressure and sweet taste are often associated with decreased pain
      sensitivity. Animal research suggests that endogenous opioids are involved in
      both these relationships. Fifty-eight healthy young adults (36 male, 22 female)
      participated in two sessions receiving a placebo tablet or 50mg of naltrexone on
      counterbalanced days. On each day, three cold-pressor tests were administered
      while the participant held a sweet solution, water, or nothing in their mouth
      when their hand was in the water. 2 Drug x 3 Solution x 2 Gender x Pre-Drug
      Resting Blood Pressure general linear models (GLM) were conducted separately for
      systolic (SBP) and diastolic (DBP) pressure. Consistent with previous research,
      significant main effects of SBP were observed in GLMs of pain tolerance and pain
      unpleasantness ratings. A main effect of solution on tolerance was seen in the
      GLM with DBP, which was qualified by an interaction of solution by blood
      pressure. Sweet taste increased pain tolerance among those with lower DBP across
      drug conditions. This suggests some overlap between mechanisms of sweet taste and
      blood pressure analgesia, without implicating opioid activity in sweet taste
      analgesia. However, the GLM of tolerance also produced a significant drug by DBP
      interaction suggesting that blood pressure-related analgesia is at least
      partially opioid-mediated. Also participants with higher DBP showed dampened mood
      reactivity to the experiment, which was partially reversible by naltrexone. These
      results are consistent with findings suggesting that endogenous opioid activity
      may contribute to generally reduced pain sensitivity, and perhaps mood
      reactivity, in those with higher BP.

PMID- 17560721
TI  - Characterization of cell proliferation in rat spinal cord following peripheral
      nerve injury and the relationship with neuropathic pain.
AB  - Glial activation is a typical response of the central nervous system to nerve
      injury. In the current investigation, we characterized the temporal and spatial
      pattern of glial proliferation, one of the most conspicuous features of glial
      activation, in relation to nerve injury-induced neuropathic pain. Using
      bromodeoxyuridine (BrdU) as a mitotic marker, we analyzed cell proliferation in
      the spinal cord, identified the phenotype of dividing cells, traced their fate,
      and correlated these phenomena with behavioural assays of the neuropathic pain
      syndrome. Our results demonstrated that peripheral nerve injury induced an early
      and transient cell proliferation, on the spinal cord ipsilateral to the nerve
      lesion which peaked at day 3 post-surgery. The majority of the proliferating
      cells were Iba-1(+) microglia, together with some NG2(+) oligodendrocyte
      progenitors, and GFAP(+) astrocytes. These newly generated cells continued to
      divide over time with the response peaking at day 14 post-injury. Microglia were
      always the predominant phenotype which made up over 60% of activated microglia
      derived from this newly generated cell population. There was a close temporal
      correlation between microglial proliferation in the spinal cord dorsal horn and
      the abnormal pain responses, suggesting a contribution of the new microglia to
      the genesis of the neuropathic pain symptoms.

PMID- 17560722
TI  - Multi-wavelength heterodyne-detected scattering-type scanning near-field optical
      microscopy.
AB  - We report on the implementation of a scattering-type scanning near-field optical
      microscope based on a heterodyne detection scheme, which has the ability to
      record near-field optical images at multiple wavelengths simultaneously. It is
      used to map out local field distribution and to investigate the dispersion
      behavior of plasmon created by nanometer-scale metallic structures. It opens up
      an unprecedented opportunity to study nano-photonics.

PMID- 17560723
TI  - Accumulation of acaricide resistance mechanisms in Rhipicephalus (Boophilus)
      microplus (Acari: Ixodidae) populations from New Caledonia Island.
AB  - Rhipicephalus (Boophilus) microplus has been pesticide-controlled for several
      decades in the pacific island of New Caledonia. Since 1996, pesticide-control has
      been based on either deltamethrin (Butox) or amitraz (Taktic) in herds harbouring
      deltamethrin-resistant ticks. In this island, the first R. microplus deltamethrin
      and amitraz-resistances were detected in 1992 and 2003, respectively. Using LPT
      bioassays, we have undertaken to update data regarding the geographical
      distribution and the physiological diversity likely to be involved in these
      resistances. We confirmed that after 17 years of intensive use of deltamethrin,
      several resistances of moderate levels (<30-fold) have evolved and/or diffused in
      any part of the island. We also evidenced that amitraz-resistant phenotypes have
      recently evolved in diverse western tick populations, although none has reached
      fixation in any tick population yet. According to synergists bioassays, the
      physiological changes involved in amitraz-resistance in New Caledonia would
      involve target modification and detoxifying P450 cytochrom oxydase(s). It may
      also involve detoxifying esterase(s) although this later point will need
      confirmation on samples bearing higher frequency of resistant phenotypes. Results
      are discussed with regard to the local evolutionary dynamics of resistance.

PMID- 17560724
TI  - Ectoparasites: future challenges in a changing world.
AB  - Ectoparasites are ubiquitous, often highly damaging and in most cases cannot be
      permanently eradicated; hence, they must usually be managed at a local scale with
      insecticides or endectocides. However, the growth in resistance, the slow rate of
      development of new actives, coupled with environmental and health concerns
      associated with the continued use of some of the existing neurotoxic
      insecticides, suggest that more sophisticated approaches to their management need
      to be identified. These approaches need to allow ectoparasite populations to be
      maintained at acceptable levels, while conserving the compounds that remain
      available. The development of integrated approaches, in which cascades of
      management tactics are deployed, with parasiticides available as one component to
      be used in requisite circumstances, may be the most appropriate route to
      achieving this aim. An essential element of such an approach is the clear
      articulation of the purpose of intervention and rational justification of the
      time-point and manner in which it is attempted. However, for this to be possible,
      considerably better information is required about the effects of ectoparasite
      abundance on animal welfare and productivity, in addition to the greater
      availability of effective alternative control tools. To this end, recent work
      undertaken at the School of Biological Sciences at the University of Bristol,
      into the use of biological control agents, off-host trapping and the selective
      treatment of more highly susceptible individuals or classes of host, is reviewed
      here.

PMID- 17560725
TI  - Biochemical characterization of a N-terminal fragment (p5) cleaved from
      fibroblast growth factor-binding protein (FGF-BP) in bovine milk in vitro.
AB  - By means of successive gel filtration on a Superdex 30 pg column and Mono S
      column chromatography, a 5-kDa polypeptide (p5) was highly purified from the low
      molecular weight (LMW) fraction separated from the partially purified lactoferrin
      (bLF) fraction of bovine milk, and biochemically characterized as a phosphate
      acceptor for two protein kinases [cAMP-dependent protein kinase (PKA) and casein
      kinase 1delta (CK1delta)] in vitro. Purified p5 was identified as a fragment (N
      terminal positions 24-51, 28 amino acid residues) cleaved from fibroblast growth
      factor-binding protein (FGF-BP, p37). Both purified p5 and synthetic p5 (sp5)
      were effectively phosphorylated by PKA, and also phosphorylated by CK1delta in
      the presence of two sulfated lipids [sulfatide or cholesterol-3-sulfate (CH-3S),
      SCS] in vitro. A novel phosphorylation site (RNRRGS) for CK1delta and a potent
      SCS-binding site (RNRR) on p5 were identified. The PKA-mediated phosphorylation
      of p5 was highly stimulated when incubated with either acidic FGF (aFGF) or bLF
      in vitro, but this phosphorylation was more sensitive to SCS than H-89 (a
      specific PKA inhibitor). Immunoprecipitate experiments revealed p5, but not the
      phosphorylated p5, to be directly bound to aFGF in vitro. These results show that
      (i) p5 has a high binding affinity with aFGF as well as bLF; (ii) the binding of
      SCS to p5 results in the selective inhibition of its phosphorylation by PKA; and
      (iii) SCS functions as an effective stimulator for the phosphorylation of p5 by
      CK1delta in vitro. In addition, p5 may play an important physiological role as a
      trafficking factor for the physiological interaction between aFGF group including
      endothelial cell growth factors and their binding proteins in vivo.

PMID- 17560726
TI  - Amyloid beta-protein potentiates tunicamycin-induced neuronal death in
      organotypic hippocampal slice cultures.
AB  - We have assessed amyloid beta protein (Abeta)-induced neurotoxicity, with and
      without added tunicamycin (TM), an inhibitor of N-glycosylation in the
      endoplasmic reticulum (ER), in rat organotypic hippocampal slice cultures (OHCs).
      In the rat OHCs cultured for 3 weeks, there was little neurotoxicity after
      treatment with Abeta(25-35) (25 microM) alone for 48 h. However, with TM alone,
      concentration-dependent neuronal death was observed at concentrations between 20
      and 80 microg/mL. When amyloid-beta protein was combined with tunicamycin
      (Abeta+TM), cell death was more acute than with TM alone. Western blot analysis
      revealed that calpain activity and the active forms of caspase-12 and caspase-3
      was increased after exposure to Abeta+TM as compared with exposure to TM alone.
      In contrast, the levels of glucose regulated protein (GRP)94, GRP78 and C/EBP
      homologous protein (CHOP) were not changed in the presence of Abeta. Abeta
      potentiation of TM neurotoxicity was reversibly blocked by S-allyl-L-cysteine
      (SAC), an organosulfur compound purified from aged garlic extract, and the L-type
      calcium channel blocker, nifedipine, in a restricted neuronal area of the OHCs.
      Simultaneously applied SAC also reversed the increases in calpain activity and
      the active forms of caspase-12 and caspase-3 by Abeta+TM with no change in the
      increased levels of GRP94, GRP78 and CHOP. These data indicate that Abeta
      facilitates the calpain-caspase-12-caspase-3 pathway, thus potentiating TM
      induced neuronal death in the hippocampus.

PMID- 17560727
TI  - Lactate, not pyruvate, is neuronal aerobic glycolysis end product: an in vitro
      electrophysiological study.
AB  - For over 60 years, a distinction has been made between aerobic and anaerobic
      glycolysis based on their respective end products: pyruvate of the former,
      lactate of the latter. Recently we hypothesized that, in the brain, both aerobic
      and anaerobic glycolysis terminate with the formation of lactate from pyruvate by
      the enzyme lactate dehydrogenase (LDH). If this hypothesis is correct, lactate
      must be the mitochondrial substrate for oxidative energy metabolism via its
      oxidation to pyruvate, plausibly by a mitochondrial LDH. Here we employed
      electrophysiology of the rat hippocampal slice preparation to test and monitor
      the effects of malonate and oxamate, two different LDH inhibitors, and glutamate,
      a neuronal activator, in experiments, the results of which support the hypothesis
      that lactate, at least in this in vitro setting, is indeed the principal end
      product of neuronal aerobic glycolysis.

PMID- 17560728
TI  - The acute ghrelin response to a psychological stress challenge does not predict
      the post-stress urge to eat.
AB  - Ghrelin is a growth hormone and cortisol secretagogue that plays an important
      role in appetite and weight regulation. It is not known whether ghrelin is
      involved in the eating response to stress in humans. In the present study we
      examined the effects of psychologically induced stress on plasma ghrelin levels
      in patients with binge-eating disorder (BED) (n=8) and in healthy subjects of
      normal (n=8) or increased (n=8) body mass index (BMI). Volunteers were subjected
      to the standardized trier social stress test (TSST). Heart rate, blood pressure,
      serum cortisol, serum prolactin, and plasma ghrelin levels were measured
      throughout the test. In addition, subjects were requested to rate their feelings
      of anxiety, tension, urge to eat uncontrollably and desire to eat sweets by means
      of a visual analog scale both before and after the TSST. There was a significant
      rise in the systolic blood pressure (p=0.003) in the study population, reflecting
      induction of physiological changes by the psychological challenge. Basal ghrelin
      levels were higher in healthy normal weight (385.4+/-79 pg/ml) than in obese
      (170.4+/-15.7 pg/ml) subjects (p<0.033). Basal ghrelin levels in patients with
      BED (240+/-40.8 pg/ml) were at an intermediate level between thin and healthy
      obese subjects, but this difference did not attain statistical significance.
      There were no differences in ghrelin levels throughout the test among the groups
      after correction for BMI, age and gender. A significant difference in the trend
      time of ghrelin was revealed when the three groups were analyzed according to
      their cortisol response to stress. Ghrelin levels increased in cortisol
      responders whereas no change or a decrease in ghrelin levels occurred in cortisol
      non-responders (p=0.038). Furthermore, a positive correlation was found between
      the change in ghrelin and the change in cortisol during TSST (r=0.444, p=0.029)
      but not between the change in ghrelin and the change in systolic blood pressure.
      The combined score of stress and anxiety was higher in subjects in the higher
      quartile of ghrelin response in comparison to the lower quartile both before
      (28.3+/-6.5 vs. 6.6+/-3.3, p=0.0077) and after (61.6+/-9 vs. 28.3+/-11.3,
      p=0.033) TSST. On the other hand, eating related scores did not differ according
      to quartiles of ghrelin response. Our findings indicate that a psychological
      stress may induce an increase in plasma ghrelin levels in humans, and that the
      post-stress induced urge for uncontrolled eating is not acutely modulated by
      stress related elevations in ghrelin levels. Furthermore, the stress induced
      increase in plasma ghrelin was associated with the acute response of serum
      cortisol to stress, but was independent of BMI or the presence of BED.

PMID- 17560730
TI  - Effects of combination treatment with mood stabilizers and mirtazapine on plasma
      concentrations of neuroactive steroids in depressed patients.
AB  - Antidepressants such as SSRIs or mirtazapine have been demonstrated to increase
      the concentrations of 3alpha-reduced neuroactive steroids throughout several
      weeks of treatment. However, no data are available on the impact of mood
      stabilizers such as lithium or carbamazepine on neuroactive steroid levels in
      depressed patients. Study 1 was performed in 26 drug-free depressed inpatients
      who were treated with either mirtazapine monotherapy (n=13) or combination
      therapy with mirtazapine and addition of lithium (n=13). Twenty drug-free
      depressed inpatients were included in study 2, receiving either mirtazapine
      monotherapy (n=10) or combination treatment with mirtazapine and carbamazepine
      (n=10). Plasma samples were taken weekly at 0800 h in the morning and quantified
      for neuroactive steroids by means of combined gas chromatography/mass
      spectrometry analysis. In study 1, the mirtazapine-induced rises in 3alpha,5alpha
      tetrahydroprogesterone and 3alpha,5beta-tetrahydroprogesterone were abolished by
      additional lithium administration, as compared to mirtazapine monotherapy. In
      study 2, the mirtazapine-evoked increase in 3alpha,5alpha-tetrahydroprogesterone
      was reversed after additional administration of carbamazepine, presumably due to
      lowered mirtazapine levels after induction of cytochrome P450 enzymes.
      Apparently, the mood stabilizers lithium and carbamazepine do not enhance but
      rather reverse the increase in plasma concentrations of 3alpha-reduced
      neuroactive steroids in depressed patients pretreated with antidepressants such
      as mirtazapine.

PMID- 17560731
TI  - Trained men show lower cortisol, heart rate and psychological responses to
      psychosocial stress compared with untrained men.
AB  - Physical activity has proven benefits for physical and psychological well-being
      and is associated with reduced responsiveness to physical stress. However, it is
      not clear to what extent physical activity also modulates the responsiveness to
      psychosocial stress. The purpose of this study was to evaluate whether the
      reduced responsiveness to physical stressors that has been observed in trained
      men can be generalized to the modulation of physiological and psychological
      responses to a psychosocial stressor. Twenty-two trained men (elite sportsmen)
      and 22 healthy untrained men were exposed to a standardized psychosocial
      laboratory stressor (Trier Social Stress Test). Adrenocortical (salivary free
      cortisol levels), autonomic (heart rate), and psychological responses (mood,
      calmness, anxiety) were repeatedly measured before and after stress exposure. In
      response to the stressor, cortisol levels and heart rate were significantly
      increased in both groups, without any baseline differences between groups.
      However, trained men exhibited significantly lower cortisol and heart rate
      responses to the stressor compared with untrained men. In addition, trained men
      showed significantly higher calmness and better mood, and a trend toward lower
      state anxiety during the stress protocol. On the whole, elite sportsmen showed
      reduced reactivity to the psychosocial stressor, characterized by lower
      adrenocortical, autonomic, and psychological stress responses. These results
      suggest that physical activity may provide a protective effect against stress
      related disorders.

PMID- 17560732
TI  - Saliva testosterone and heart rate variability in the professional symphony
      orchestra after "public faintings" of an orchestra member.
AB  - Musicians are sensitive to changes in their work environment. A 2-year
      longitudinal study with repeated observations was performed in two professional
      symphony orchestras. A representative sample from each one of them was selected,
      15 and 16 members respectively. In one of them a wind player fainted twice in
      front of the audience shortly preceding and coinciding with the start of the
      study. Changes in two indicators that reflect regenerative/anabolic and
      parasympathetic tone, saliva testosterone concentration (STC) and very low
      frequency power (VLFP) in heart rate variability were followed in relation to
      this dramatic change. Saliva samples and 24-h ECG heart rate variability
      recordings were collected on five occasions every 6 months during a 2-year
      period. No changes were seen in the control orchestra whereas the levels showed a
      pronounced rise in the intervention orchestra during the first part of the study,
      starting from low levels. VLFP showed a similar pattern, with initially low and
      then rising level in the intervention orchestra and higher stable level in the
      other group. In the total study group, a rise in STC over the whole observation
      period was significantly correlated with increase in VLFP and also significantly
      correlated with a decrease in low/high-frequency power ratio in heart rate
      variability. The changes observed in the anabolic/regenerative STC and the
      parasympathetically influenced VLFP may reflect changes in the work environment
      associated with the faintings.

PMID- 17560733
TI  - Trigger osteoclast formation and activation: molecular treatment strategy of
      delayed tooth eruption.
AB  - Delayed tooth eruption (DTE) is the emergence of a tooth into the oral cavity at
      a time that delays significantly from norms. It causes a significant impact on a
      patient's oral health. Some methods have been suggested to rescue the delayed
      tooth eruption. However, no approach aims to accelerate the biological process of
      tooth eruption and rescue these eruption disorders. Recent researches have shown
      that tooth eruption depends on the presence of osteoclasts to create an eruption
      pathway through the alveolar bone. We postulate a new approach that targets
      osteoclast formation and activation to accelerate the eruption of the affected
      tooth. These strategies include stimulating osteoclastogenesis by applying the
      cytokines or small molecules, such as TNF-alpha, IL-1 alpha and MCP-1; triggering
      osteoclast differentiation by applying molecules associated RANKL signaling, such
      as RANKL-Fc and OPG antibody; enhancing the function of osteoclasts by applying
      proteinases, such as CTSK. For the clinical point of view, we can inject these
      molecules in the oral mucosa of the affected tooth to induce bone resorption,
      then to rebuild the pathway of tooth eruption.

PMID- 17560734
TI  - Results of bladder-conserving treatment, consisting of brachytherapy combined
      with limited surgery and external beam radiotherapy, for patients with solitary
      T1-T3 bladder tumors less than 5 cm in diameter.
AB  - PURPOSE: To evaluate the long-term, local relapse-free, distant metastasis-free,
      and overall survival rates in patients with a solitary bladder tumor <5 cm in
      diameter who were treated with external beam radiotherapy, limited surgery, and
      brachytherapy. METHODS AND MATERIALS: The results of 122 patients after bladder
      saving treatment were analyzed. After EBRT, the patients underwent cystotomy, and
      catheters were implanted. Of the 122 patients, 99 were treated with a continuous
      low-dose-rate technique and 23 patients with a pulsed-dose-rate technique. The
      median follow-up period was 5 years. RESULTS: The 5-year local and distant
      relapse-free survival rate was 76% and 83%, respectively. The 5 and 10-year
      relapse-free survival rate was 69% and 66%, respectively. For overall survival,
      the corresponding rates were 73% and 49%. Toxicity was low. No differences were
      found between the continuous low-dose-rate and pulsed-dose-rate groups.
      CONCLUSION: The results of our study have shown that external beam radiotherapy
      followed by brachytherapy as a bladder-saving treatment for a selected group of
      patients with bladder cancer yields excellent local tumor control and low
      toxicity.

PMID- 17560735
TI  - Impact of radiation-induced xerostomia on quality of life after primary
      radiotherapy among patients with head and neck cancer.
AB  - PURPOSE: To investigate the impact of xerostomia on overall quality of life (QoL)
      outcome and related dimensions among head and neck cancer patients treated with
      primary radiotherapy. METHODS AND MATERIALS: A total of 288 patients with Stage I
      IV disease without distant metastases were included. Late xerostomia according to
      the Radiation Therapy Oncology Group (RTOG-xerostomia) and QoL (European
      Organization for Research and Treatment of Cancer QLC-C30) were assessed at
      baseline and every 6th month from 6 months to 24 months after radiotherapy.
      RESULTS: A significant association was found between RTOG-xerostomia and overall
      QoL outcome (effect size [ES] 0.07, p < 0.001). A significant relationship with
      global QoL, all functioning scales, and fatigue and insomnia was observed. A
      significant interaction term was present between RTOG-xerostomia and gender and
      between RTOG-xerostomia and age. In terms of gender, RTOG-xerostomia had a larger
      impact on overall QoL outcome in women (ES 0.13 for women vs. 0.07 for men).
      Furthermore, in women ES on individual scales were larger, and a marked worsening
      was observed with increasing RTOG-xerostomia. No different ES according to age
      was seen (ES 0.10 for 18-65 years vs. 0.08 for >65 years). An analysis of the
      impact of RTOG-xerostomia on overall QoL outcome over time showed an increase
      from 0.09 at 6 months to 0.22 at 24 months. With elapsing time, a worsening was
      found for these individual scales with increasing RTOG-xerostomia. CONCLUSIONS:
      The results of this prospective study are the first to show a significant impact
      of radiation-induced xerostomia on QoL. Although the incidence of Grade > or =2
      RTOG-xerostomia decreases with time, its impact on QoL increases. This finding
      emphasizes the importance of prevention of xerostomia.

PMID- 17560736
TI  - Long-term survivors using intraoperative radiotherapy for recurrent gynecologic
      malignancies.
AB  - PURPOSE: To analyze the outcomes of therapy and identify prognostic factors for
      patients treated with surgery followed by intraoperative radiotherapy (IORT) for
      gynecologic malignancies at a single institution. METHODS AND MATERIALS: We
      performed a retrospective review of 36 consecutive patients treated with IORT to
      44 sites with mean follow-up of 50 months. The primary site was the cervix in
      47%, endometrium in 31%, vulva in 14%, vagina in 6%, and fallopian tubes in 3%.
      Previous RT had failed in 72% of patients, and 89% had recurrent disease. Of 38
      IORT sessions, 84% included maximal cytoreductive surgery, including 18%
      exenterations. The mean age was 52 years (range, 30-74), mean tumor size was 5 cm
      (range, 0.5-12), previous disease-free interval was 32 months (range, 0-177), and
      mean IORT dose was 1,152 cGy (range, 600-1,750). RT and systemic therapy after
      IORT were given to 53% and 24% of the cohort, respectively. The outcomes measured
      were locoregional control (LRC), distant metastasis-free survival (DMFS), disease
      specific survival (DSS), and treatment-related complications. RESULTS: The Kaplan
      Meier 5-year LRC, DMFS, and DSS probability for the whole group was 44%, 51%, and
      47%, respectively. For cervical cancer patients, the Kaplan-Meier 5-year LRC,
      DMFS, and DSS estimate was 45%, 60%, and 46%, respectively. The prognostic
      factors found on multivariate analysis (p <or= 0.05) were the disease-free
      interval for LRC, tumor size for DMFS, and cervical primary, previous surgery,
      and locoregional relapse for DSS. Our cohort had 10 Grade 3-4 complications
      associated with treatment (surgery and IORT) and a Kaplan-Meier 5-year Grade 3-4
      complication-free survival rate of 72%. CONCLUSIONS: Survival for pelvic
      recurrence of gynecologic cancer is poor (range, 0-25%). IORT after surgery seems
      to confer long-term local control in carefully selected patients.

PMID- 17560737
TI  - Results of the phase I dose-escalating study of motexafin gadolinium with
      standard radiotherapy in patients with glioblastoma multiforme.
AB  - PURPOSE: Motexafin gadolinium (MGd) is a putative radiation enhancer initially
      evaluated in patients with brain metastases. This Phase I trial studied the
      safety and tolerability of a 2-6-week course (10-22 doses) of MGd with
      radiotherapy for glioblastoma multiforme. METHODS AND MATERIALS: A total of 33
      glioblastoma multiforme patients received one of seven MGd regimens starting at
      10 doses of 4 mg/kg/d MGd and escalating to 22 doses of 5.3 mg/kg/d MGd (5 or 10
      daily doses then three times per week). The National Cancer Institute Cancer
      Therapy Evaluation Program toxicity and stopping rules were applied. RESULTS: The
      maximal tolerated dose was 5.0 mg/kg/d MGd (5 d/wk for 2 weeks, then three times
      per week) for 22 doses. The dose-limiting toxicity was reversible transaminase
      elevation. Adverse reactions included rash/pruritus (45%), chills/fever (30%),
      and self-limiting vesiculobullous rash of the thumb and fingers (42%). The median
      survival of 17.6 months prompted a case-matched analysis. In the case-matched
      analysis, the MGd patients had a median survival of 16.1 months (n = 31) compared
      with the matched Radiation Therapy Oncology Group database patients with a median
      survival of 11.8 months (hazard ratio, 0.43; 95% confidence interval, 0.20-0.94).
      CONCLUSION: The maximal tolerated dose of MGd with radiotherapy for glioblastoma
      multiforme in this study was 5 mg/kg/d for 22 doses (daily for 2 weeks, then
      three times weekly). The baseline survival calculations suggest progression to
      Phase II trials is appropriate, with the addition of MGd to radiotherapy with
      concurrent and adjuvant temozolomide.

PMID- 17560738
TI  - Comparative analysis of active constituents in Centella asiatica samples from
      Madagascar: application for ex situ conservation and clonal propagation.
AB  - A comparative quantitative analysis of the active triterpenoids in Centella
      asiatica samples collected in different locations in Madagascar was carried out
      to evaluate the natural variability in triterpenoid content and to select elite
      samples for further ex situ germplasm conservation and clonal propagation. The
      highest asiaticoside content (6.42%) was measured in samples collected in Mangoro
      region. In vitro propagation of C. asiatica was successfully achieved in hormone
      free medium. Although lower asiaticoside content was detected in 8-week-old vitro
      plants, the Mangoro sample still showed the highest content in this triterpenoid
      constituent (1.78%). Acetoxycentellynol, a C(15)-polyacetylene, was found to be
      accumulated up to 18 times more in in vitro plants as compared to plant material
      collected in situ.

PMID- 17560739
TI  - Effects of alcohol on psychomotor performance and perceived impairment in heavy
      binge social drinkers.
AB  - Alcohol intoxication often results in negative consequences; however, specific
      behavioral and subjective effects vary as a function of individual differences.
      The present study utilized an alcohol challenge paradigm to examine whether heavy
      binge social drinkers (HD; n=77), compared to light social drinkers (LD; n=55),
      exhibit: (1) greater tolerance in psychomotor task performance under the
      influence of alcohol, and (2) differential perceptions of the impairing effects
      of alcohol. The study included three test sessions in which participants consumed
      either a low (0.4 g/kg) or a high (0.8 g/kg) dose of ethanol or a placebo
      beverage administered in random order and counterbalanced within group.
      Participants completed the Digit-Symbol Substitution Task (DSST) and the Grooved
      Pegboard at pre-drink baseline and at multiple time points after beverage
      consumption. They also completed a scale of perceived impairment at several
      intervals after beverage consumption. Ethanol impaired performance at the high
      dose, but not at the low dose (ps<.001). The groups exhibited similar alcohol
      induced impairment. However, HD reported lower self-perceived impairment compared
      to LD, particularly during the early portion of the blood alcohol curve when
      actual impairment was most pronounced (p<.001). Thus, this study extends prior
      research in that habitual binge social drinking does not appear to be associated
      with tolerance to alcohol's impairing effects on select psychomotor skills.
      Further, results may have implications for alcohol-related harm as binge social
      drinkers regularly consume intoxicating doses of alcohol but may not be aware of
      the physical and cognitive impairments produced by alcohol.

PMID- 17560740
TI  - Conjugational transfer system to shuttle giant DNA cloned by Bacillus subtilis
      genome (BGM) vector.
AB  - The Bacillus subtilis GenoMe (BGM) vector was designed as a versatile vector for
      the cloning of giant DNA segments. Cloned DNA in the BGM can be retrieved to a
      plasmid using our Bacillus recombinational transfer (BReT) method that takes
      advantage of competent cell transformation. However, delivery of the plasmid to a
      different B. subtilis strain by the normal transformation method is hampered by
      DNA size-related inefficiency. Therefore, we designed a novel method,
      conjugational plasmid-mediated DNA retrieval and transfer (CReT) from the BGM
      vector, and investigated conjugational transmission to traverse DNA between cells
      to circumvent the transformation-induced size limitation. pLS20, a 65-kb plasmid
      capable of conjugational transfer between B. subtilis strains, was modified to
      retrieve DNA cloned in the BGM vector by homologous recombination during normal
      culture. As the plasmid copy number was estimated to be 3, the retrieval plasmid
      was selected using increased numbers of marker genes derived from the retrieved
      DNA. We applied this method to retrieve Synechocystis genome segments up to 90 kb
      in length. We observed retrieved plasmid transfers between B. subtilis strains by
      conjugation in the absence of structural alterations in the DNA fragment. Our
      observations extend DNA transfer protocols over previously exploited size ranges.

PMID- 17560741
TI  - Characterization, molecular cloning and localization of calreticulin in Eisenia
      fetida earthworms.
AB  - Calreticulin is a highly conserved calcium-binding protein affecting many
      cellular processes inside and outside of the endoplasmic reticulum (ER). It
      participates in the regulation of Ca(2+) homeostasis, acts as a chaperone and
      modulates gene transcription, integrin-mediated cell signalling as well as cell
      adhesion. Here we report on the sequence characterization of a calreticulin
      coding cDNA of Eisenia fetida earthworms. The neighbor-joining phylogeny tree
      constructed based on the deduced amino acid sequence indicates a common origin of
      the E. fetida calreticulin molecule and that of mollusks. A polyclonal anti
      calreticulin antibody used for immunocytochemistry and immunohistochemistry
      localized the protein in the mesenchymal lining of the coelomic cavity and in
      coelomocytes of E. fetida. In situ hybridization revealed high expression of E.
      fetida calreticulin in various cells and tissues, namely epidermis, neurons of
      the ventral nerve cord, intestine, sperms, body wall muscles and some
      coelomocytes. Real-time PCR confirmed the strong expression of calreticulin in
      the nervous system, particularly in cerebral ganglia, in body wall muscles and in
      seminal vesicles. Moreover, a high calreticulin expression was measured in the
      muscular pharynx.

PMID- 17560742
TI  - Gene expression and tissue distribution of cytoglobin and myoglobin in the
      Amphibia and Reptilia: possible compensation of myoglobin with cytoglobin in
      skeletal muscle cells of anurans that lack the myoglobin gene.
AB  - Cytoglobin (Cygb), a recently discovered vertebrate cytoplasmic heme-binding
      globin, is considered to be in a clade with vertebrate myoglobin (Mb), which is
      exclusively distributed in the cytoplasm of cardiac and skeletal muscles as an
      oxygen storage protein. GenBank databases (NCBI and JGI) and gene synteny
      analyses showed the absence of the Mb gene (mb) in two anuran amphibians, Xenopus
      laevis and X. tropicalis. Here we conducted comparative studies on the gene
      expression and tissue distribution of Cygb and Mb in anuran and reptilian
      tissues. Cygb and Mb genes were cloned from a reptile, iguana (Iguana iguana).
      Two types of cygb (cygb-1 and -2) were cloned, with lengths of 1066 and 1034 bp,
      and 196 and 193 amino acid residues, respectively. Their nucleotide and amino
      acid sequence identities were 90 and 87%, respectively. The Mb gene covered 1416
      bp with an open reading frame of 465 bp, giving rise to a 154 amino acid protein.
      The distal ligand-binding histidine at E7, the proximal heme-binding histidine at
      F8, and the phenylalanine residue at CD1 were conserved in Mb and Cygb. The
      nucleotide and amino acid sequence identity of I. iguana cygb-1 and cygb-2
      against X. laevis cygb were approximately 67% and 65%, respectively. RT-PCR
      demonstrated that X. laevis cygb was uniquely expressed in the heart and skeletal
      muscles, and faintly in the liver and spleen, which was quite contrasted with
      Iguana and the other vertebrates, where mb is exclusively expressed in the heart
      and skeletal muscles. Immunohistochemical analyses showed the distribution of
      Cygb in the cytoplasm of skeletal muscle cells. Interestingly, Cygb in the heart
      was localized in the nuclei. Considering the absence of mb in the Anura, we
      hypothesize that Cygb in muscle cells of anurans compensates for the lack of Mb
      for the storage and intracellular transportation of oxygen.

PMID- 17560743
TI  - Evaluation of radiometric faecal culture and direct PCR on pooled faeces for
      detection of Mycobacterium avium subsp. paratuberculosis in cattle.
AB  - Dilution rates for pooled faecal culture (PFC) and direct IS900 polymerase chain
      reaction (D-PCR) tests were evaluated on faecal samples from infected cows mixed
      with uninfected faeces in dilutions from 1 in 5 to 1 in 50. PFC was performed by
      radiometric culture, with confirmation by IS900 PCR and restriction endonuclease
      analysis (PCR/REA) on growth, and by mycobactin dependency testing on solid
      medium. Using 37 culture positive faecal samples from 12 subclinical cows, 83.8%
      and 94.6% of samples were confirmed positive in the PFC assay at dilutions of 1
      in 50 and 1 in 30, respectively. Lower dilutions (1 in 5 to 1 in 20) provided
      only marginally better sensitivity, and confirmation of PFC growth by PCR/REA was
      significantly more sensitive than mycobactin dependency. D-PCR had significantly
      lower sensitivity than PFC confirmed by PCR/REA, with pools of 1 in 50, 30, 10
      and 5 yielding positive results in 64.9%, 70.3%, 78.4% and 83.8% of samples,
      respectively. Cattle considered to be shedding 1.5 x 10(6) viable M. avium subsp.
      paratuberculosis (Map)/g faeces (on the basis of estimated losses in processing
      and growth rates in radiometric broth) were positive at dilutions up to 1 in 50
      in the PFC and D-PCR. Those shedding 5 x 10(5) viable Map/g were positive in the
      PFC at dilutions up to 1 in 40, but required a 1 in 10 dilution or less for D
      PCR. The results suggest that for cattle shedding relatively high concentrations
      of Map in faeces (>2 x 10(5) viable Map/g), maximal dilutions of 1 in 30 for PFC
      and 1 in 10 for D-PCR would be applicable.

PMID- 17560744
TI  - Immunization by intrabronchial administration to 1-week-old foals of an unmarked
      double gene disruption strain of Rhodococcus equi strain 103+.
AB  - Rhodococcus equi causes fatal granulomatous pneumonia in foals and
      immunocompromised animals and humans. However, there is no effective vaccine
      against this infection. In this study, the chromosomal genes isocitrate lyase
      (icl) and cholesterol oxidase (choE) were chosen as targets for mutation and
      assessment of the double mutant as an intrabronchial vaccine in 1-week-old foals.
      Using a modification of a suicide plasmid previously developed in this
      laboratory, we developed a choE-icl unmarked deletion mutant of R. equi strain
      103+. Five 1-week-old foals were infected intrabronchially with the mutant and
      challenged intrabronchially with the parent, virulent, strain 2 weeks later.
      Three of the foals were protected against pneumonia caused by the virulent
      strain, but the other two foals developed pneumonia caused by the mutant strain
      during the post-challenge period. Since infection of 3-week-old foals by an icl
      mutant in an earlier study had shown complete attenuation of the strain, we
      conclude that a proportion of foals in the 1st week or so of life are predisposed
      to developing R. equi pneumonia because of an inability to mount an effective
      immune response. This has been suspected previously but this is the first time
      that this has been demonstrated experimentally.

PMID- 17560745
TI  - Outer membrane permeability for nonpolar antimicrobial agents underlies extreme
      susceptibility of Pasteurella multocida to the hydrophobic biocide triclosan.
AB  - Pasteurella multocida exhibits nonspecific susceptibility to nonpolar
      antimicrobial agents such as triclosan, despite possessing an ultrastructurally
      typical gram-negative cell envelope. Capsulated and noncapsulated cell surface
      variants were examined to investigate the role outer membrane permeability plays
      in triclosan susceptibility. Test strains were unable to initiate growth in the
      presence of bile salts and were susceptible to triclosan with minimal inhibitory
      concentrations (MICs) ranging from 0.06 to 0.25 microg/ml. Disk agar diffusion
      bioassays revealed triclosan susceptibility to be dose dependent and all strains
      were susceptible to the hydrophobic antibiotics novobiocin, rifamycin SV, and
      chloramphenicol. Triclosan minimal bactericidal concentrations were greater than
      MICs, thereby suggesting that dose dependency reflected both bacteriostatic and
      bactericidal effects. Total and viable cell density growth kinetic determinations
      revealed a triclosan concentration of 2.0 microg/ml resulted in loss of batch
      culture viability within 4-24 h. Concentrations of 0.02 and 0.2 microg/ml exerted
      either a bacteriostatic or bactericidal effect depending on the strain. Uptake of
      the hydrophobic probe 1-N-phenylnaphthylamine was greater in P. multocida strains
      than refractory control organisms Pseudomonas aeruginosa and Escherichia coli
      thereby suggesting the presence of phospholipid bilayer regions in the outer
      membrane. Because triclosan inhibits a conserved enoyl-ACP reductase necessary
      for bacterial fatty acid biosynthesis, these data support the notion that extreme
      susceptibility in P. multocida is due to the general inability of the outer
      membrane to exclude nonpolar compounds. Moreover, susceptibility is independent
      of the presence of capsular material and the biocide is bactericidal in a
      concentration dependent manner.

PMID- 17560746
TI  - Ingestion of pointed objects in a complex suicide.
AB  - A 51-year-old woman with a psychiatric history of depression and drug abuse was
      found hanged in her bedroom. The ligature was a scarf attached to the door
      handle. The autopsy findings suggested that two methods of suicide had been used
      one after the other. In the first stage, numerous nails, pins and needles were
      swallowed; in the second stage, the suicide was completed by hanging.

PMID- 17560747
TI  - [Diagnosis and epidemiological surveillance of influenza and respiratory
      syncytial virus infections: interest of multiplex PCR].
AB  - OBJECTIVE: Respiratory infections require a rapid etiological diagnosis for
      efficient management of cases. We evaluated multiplex PCR used for the diagnosis
      and the epidemiological surveillance of influenza and respiratory syncytial virus
      (RSV) infections. PATIENTS AND METHODS: Our study included 278 patients (mean
      age: 37.2+/-22.9 years) with flu or flu-like syndromes, consulting physicians
      affiliated with the GROG Poitou-Charentes or hospitalized in the Poitiers
      teaching hospital. A multiplex PCR detecting A(H3), A(H1) and B influenza
      viruses, and RSV A and B, was performed with both a direct examination by
      immunofluorescence and cell-culture. RESULTS: We diagnosed a viral infection in
      139 (50.0%) patients: 99 cases of influenza A(H3), 2 cases of influenza A(H1), 28
      cases of influenza B and 11 cases of RSV infections. The diagnosis yield in GROG
      patients (52.3%) was significantly higher than that observed in hospitalized
      patients (34.5%) (P=0.04). All techniques were correlated in 61% of cases. The
      multiplex PCR yielded 22.3% more positive samples compared to the conventional
      techniques. All positive samples by conventional techniques were also positive by
      multiplex PCR. We observed a perfect correlation between viral types and subtypes
      determined by PCR and cell-culture. CONCLUSION: Multiplex PCR is a sensitive
      technique allowing an efficient and rapid diagnosis of respiratory infections due
      to influenza and RSV.

PMID- 17560748
TI  - Sulci density map to aid in use of apparent diffusion coefficient for therapy
      evaluation.
AB  - In order to more accurately asses variations in the apparent diffusion
      coefficient used for therapy evaluation, we have studied the variation in sulci
      density in the human brain. Sagittal, axial and coronal magnetic resonance
      imaging scans have been analyzed to determine the change of the coefficient of
      variance of pixel intensity as a function of position. In the sagittal direction,
      relative to the 50% most medial slices, we find an 11.0%+/-4.8% (S.D.) decrease
      in the next 25% (12.5% on each side) of the slices. The most lateral 25% of the
      slices had less of a decrease and more variation: 7.0%+/-12.2%. Similar
      variations were observed in axial and coronal scans.

PMID- 17560749
TI  - Determination of hydrochlorothiazide in human plasma by liquid
      chromatography/tandem mass spectrometry.
AB  - In this study, a fast and sensitive liquid chromatography/tandem mass
      spectrometry method for determination of hydrochlorothiazide in human plasma was
      developed and validated. The analyte and irbesartan, used as the internal
      standard, were precipitated and extracted from plasma using methanol. Analysis
      was performed on a Phenomenex Kromasil C(8) column with water and methanol
      (27:73, v/v) as the mobile phase. Linearity was assessed from 0.78 to 200 ng/mL
      in plasma. The analytical method proved to be applicable in a pharmacokinetic
      study after oral administration of 12 mg hydrochlorothiazide tablets to 20
      healthy volunteers.

PMID- 17560750
TI  - Validation of a dissolution method with HPLC analysis for lasofoxifene tartrate
      low dose tablets.
AB  - A dissolution method with high performance liquid chromatography (HPLC) analysis
      was validated for an immediate release low dose tablet formulation. The method
      was validated to meet requirements for a global regulatory filing and this
      validation included specificity, precision, linearity, accuracy and range.
      Validation of precision included an intermediate precision study using an
      experimental design in order to satisfy Japanese regulatory requirements. In
      addition, filter suitability, standard and sample solution stability and method
      robustness were demonstrated. A statistical design of experiments was used for
      the robustness evaluation of both the dissolution method and the HPLC analysis
      method. All results were acceptable and confirmed that the method is suitable for
      its intended use.

PMID- 17560751
TI  - Quantitative determination of unbound cefoperazone in rat bile using
      microdialysis and liquid chromatography.
AB  - Cefoperazone is a third generation cephalosporin antibiotic with a broad spectrum
      against gram-positive and gram-negative bacteria. It is clinically effective in
      the treatment of the biliary tract infections. In the present study, we utilized
      microdialysis sampling technique with shunt linear probe for continuous
      monitoring levels of cefoperazone from rat biliary ducts. The effects of
      berberine (a potential P-glycoprotein enhancer) pretreatment were also evaluated.
      Analysis of cefoperazone in the dialysates was achieved using a reversed phase RP
      18 column (250 mm x 4.6 mm i.d.; particle size 5 microm) maintained at ambient
      temperature. The mobile phase comprised 100 mM monosodium phosphate (pH 5.5)
      methanol (70:30, v/v), and the flow rate of the mobile phase was 1 ml/min. The UV
      detector wavelength was set at 254 nm. The area under the concentration-time
      curve and elimination half-life of cefoperazone were about 242.3+/-13.4 min mg/ml
      and 64.1+/-28.2 min, respectively. No significant effect was showed on the
      pharmacokinetics of cefoperazone with berberine pretreatment. This study
      represents a successful application of biliary microdialysis sampling technique,
      which is feasible for pharmacokinetic and biliary drug excretion studies.

PMID- 17560752
TI  - Neurogenesis of GABAergic cells in the retina of malnourished rats.
AB  - The present study investigated how prenatal protein malnutrition affects the
      neurogenesis of GABAergic cells in the retina. Rats were treated with a multi
      deficient diet, with only 8% of protein that was administered during the
      gestational and suckling periods. Pregnant mothers and pups from malnourished and
      control (fed with 22% protein) groups received a single intra-peritoneal
      injection of [3H]-thymidine at six developmental ages, from E14 to PN4, and the
      pups were sacrificed at PN18. Eyes were enucleated and cryosections of the retina
      were double labeled for GABA-immunocytochemistry and for autoradiography. The
      percentage of double labeled cells, in the retinal inner nuclear and ganglion
      cell layers, was determined for both groups. Qualitative and quantitative results
      showed that double labeled cells [GABA+/thymidine+] were present since E14, when
      mitotic activity for GABAergic cells starts, in both GCL and INL layers. The peak
      rate of GABAergic cell generation was reached in control animals injected with
      [3H]-thymidine at E18 in both central and peripheral sectors of the retina, but
      only at E20 in the malnourished group. The generation of cells of GABA phenotype
      showed a significant delay in both layers of the retina in the malnourished
      group. At PN4, close to the age that GABAergic mitotic activity ends in the
      control group, double labeled cells were significantly higher in the malnourished
      group. Our data showed a delay in GABAergic cell generation in the malnourished
      group when compared to the control group that might result in significant
      functional consequences in the developing retina.

PMID- 17560753
TI  - PPARgamma and GLUT-4 expression as developmental regulators/markers for
      preadipocyte differentiation into an adipocyte.
AB  - In this document, we have integrated knowledge about two major cellular markers
      found in cells of the adipocyte lineage (an adipogenic marker and a metabolic
      marker). This review provides information as to how differentiation of a cell
      (such as an adipofibroblast, fibroblast or preadipocyte) to become a viable (and
      new) adipocyte is under different regulation than that experienced by an immature
      adipocyte that is just beginning to accumulate lipid. The differentiation, prior
      to lipid-filling, involves PPARgamma. Subsequently, lipid-filling of the
      adipocyte relies on a late subset of genes and, depending on depot specificity,
      involves GLUT-4 or any number of other metabolic markers.

PMID- 17560754
TI  - The role of radiotherapy in treating small early invasive breast cancer.
AB  - AIM: The aim of the study was to identify if radiotherapy can be safely avoided
      in a selected subgroup of largely screening detected small invasive breast
      cancer. METHODS: One hundred and eighty-eight patients with node negative
      invasive early breast cancer < or =1cm (< or =T1b) treated in our centre between
      1990 and 2004 were retrospectively followed for local, regional and distant
      recurrences. Treatment involved adequate local excision by breast conserving
      surgery (BCS). Axillary staging was performed by a four node axillary sampling
      until 2000, following which sentinel lymph node sampling was employed. All
      sections were assessed histologically by haematoxylin and eosin stained sections.
      The inked margins were reported as being involved, close and clear. Radiotherapy
      (RT) was employed only if the resected margins were inadequate, and in those with
      involved axillary nodes who refused further completion axillary clearance.
      RESULTS: Ninety-four patients (Group A) had BCS alone and 79 patients (Group B)
      had both BCS and RT. There was no ipsilateral breast tumour recurrence (IBTR) in
      88 patients in Group A, corresponding to an actuarial freedom from IBTR of 96%,
      91% and 88.1% at 5 years, 8 years and 9 years. In Group B, there was no IBTR in
      75 patients corresponding to an actuarial freedom from IBTR of 97%, 94.9% and
      90.6% at 5 years, 8 years and 10 years. CONCLUSION: Our experience over 14 years
      has shown that it is possible to safely avoid radiotherapy in a selected subgroup
      of small invasive breast cancer.

PMID- 17560755
TI  - [Nociceptive cancer pain in adult patients: statement about guidelines related to
      the use of antinociceptive medicine].
AB  - OBJECTIVE: The World Health Organization (WHO) published guidelines to improve
      cancer pain control which allow to relieve noceptive cancer pain in 80% of adult
      patients. Nevertheless WHO recommendations do not include: various ways to start
      morphine treatment, how to manage opioids adverse effects, severe cancer pain
      management, postoperative pain and procedure-relatived pain. The goal of this
      review is to discuss these issues. DATA SOURCES: The data were retrieved from
      PubMed years 2001 to 2006 (keywords used alone or in combination were: opioids,
      cancer, pain, pain killers, rotation, intraspinal, ketamine, side effects), the
      "Standard, Options and Recommendations on cancer nociceptive pain treatments for
      adult patients" published by the French Union of Comprehensive Cancer Centers
      (FNCLCC; Federation nationale des centres de lutte contre le cancer) and the
      European Association for Palliative Care (EAPC) recommendations on morphine and
      alternative opioids in cancer pain. Data also include an analysis of studies
      before 2001 which give information about the pharmacokinetic data of transdermal
      and transmucosal fentanyl. STUDY SELECTION: Studies written in English or French
      related to the medical treatments (commercialized in France) for nociceptive
      cancer pain for adult patients were analyzed. Analyzed articles were clinical or
      experimental studies or metaanalyses. Studies on neuropathic cancer pain,
      editorials and letters to the editor were discarded. RESULTS: Nociceptive cancer
      pain is characterized by its frequent instability. More than 50% of patients have
      paroxystic painful accesses (PPA), either spontaneous or induced by care or
      mobilizations. Morphine is the main treatment but the prescription of controlled
      release morphine must be associated with the prescription of immediate-release
      morphine to treat the PPA or to transmucosal fentanyl which has a faster onset of
      action than immediate-release morphine. Morphine treatment can be introduced
      either by immediate-release morphine or by controlled-release morphine. The
      introduction of immediate-release morphine is recommended for old or fragile
      patients, patients with denutrition, hepatic or renal failure. For patients
      suffering unbearable side effects under morphine or morphine resistant pain,
      opioid rotation or intravenous morphine or fentanyl are recommended. Spinal
      opioids administration (by epidural or intrathecal routes) is most often
      indicated in patients with very severe and resistant pain in terminal disease. In
      the postoperative period, previous pain treatment must be maintained or
      increased. Pain bounded to care procedures must be prevented with various and
      associated treatments: for example, mixed topics lidocaine-prilocaine for venous
      or arterial punctures; infiltration of local anaesthetics and inhalation of an
      oxygen - nitrous oxide mixture for medullary biopsies. CONCLUSION: Oral immediate
      or controlled release morphine is the most common and effective pain treatment
      for most patients with nociceptive cancer pain but rotation with other opioids or
      alternative routes of administration must be discussed quickly if pain persits or
      if adverse effects occur.

PMID- 17560756
TI  - Thyroid hormone receptor and IGF1/IGFR systems: possible relations in the human
      heart.
AB  - Thyroid hormone (TH) and insulin growth factor 1 (IGF1) systems both play crucial
      roles in the regulation of cardiac remodeling and hypertrophy processes. The
      mediation of this regulation is attributed to specific thyroid hormone receptors
      (TRs) and to the IGF1 receptor (IGF1R). In humans, two TR genes are expressed in
      the heart, TRalpha and TRbeta. Each gene generates two isoforms: TRalpha1,
      TRalpha2 and TRbeta1, TRbeta2. The aim of the present work was to study the local
      thyroid hormone and IGF1 signaling in human myocardium through the evaluation of
      the gene expression of TRalpha1, TRalpha2, TRbeta1 and IGF1R among atrial and
      ventricular biopsies obtained from patients undergoing cardiac surgery. Moreover,
      we evaluated possible correlations between TR and IGF1/IGF1R systems. Eighteen
      clinically and biochemically euthyroid patients (aged 68.3+/-3.2years, mean+/
      SEM) without overt heart failure (Ejection Fraction (EF), 46.4+/-2.8%; Left
      Ventricular End Diastolic Diameter (LVEDD), 54.3+/-1.2mm, mean+/-SEM; NYHA I-II)
      were enrolled in the study: 13 undergoing aorto-coronary bypass and 5 undergoing
      valve replacement (aortic/mitral valve). The examination of total RNA, using real
      time PCR (LightCycler Technology) confirmed the expression of specific mRNAs
      encoding TRalpha1, TRalpha2, TRbeta1 and both IGF1 and IGF1R. We found that the
      three TR genes are co-expressed in the human atrium and ventricle. The finding of
      a strong correlation among IGF1R and the three TR genes expressed in the atrium
      (p<0.001) and among the three TRs in the atrium (p<0.001) suggests the
      interesting possibility that the two systems, TRs and IGF1R could also be
      functionally associated.

PMID- 17560757
TI  - [Antibiotics: perfusion is no longer automatic].

PMID- 17560758
TI  - [Infertility and testicular seminoma].
AB  - INTRODUCTION: Infertility in men may be associated with an elevated risk of
      testicular cancer. The authors report a case of testicular seminoma discovered
      fortuitously during a workup for infertility. CASE: A 30 year-old male was seen
      for infertility. Physical examination and testicular ultrasonography were normal.
      The sperm count found oligoasthenospermia related to the excretory ducts. The
      patient underwent testicular biopsies for infertility, which showed an
      intratubular germ cell tumor. Tumor markers (beta HCG, alpha FP, LDH) were
      normal. Computed tomography was normal for the thorax, abdomen, and pelvis. We
      performed an inguinal orchiectomy. The pathology examination found seminoma, at a
      pT1 stage. One course of chemotherapy followed. DISCUSSION: The incidence of
      testicular cancer is increasing throughout the world. Recent studies show a
      strong relation between infertility and an increased risk of testicular cancer,
      and some authors even suggest a causal relation.

PMID- 17560759
TI  - [Bird-breeders' disease].

PMID- 17560760
TI  - [Epidemiology of dementia].
AB  - Dementia is a major public health problem and its burden will increase in the 30
      years to come. Prevalence increases with age and incidence is slightly higher in
      women than men, especially after the age of 80 years. Survival after the onset of
      dementia is approximately 5 years. Lifestyle and health habits are a keystone for
      dementia: risk factors include physical, intellectual and social activity and
      nutritional habits. Data from well-conducted intervention studies are necessary
      to show whether better care for hypertension, diabetes, and dyslipidemia might
      decrease the incidence of dementia.

PMID- 17560761
TI  - [Osteogenesis imperfecta].
AB  - Osteogenesis imperfecta is a genetic disorder that causes increased bone
      fragility and low bone mass. Osteogenesis imperfecta is a rare disease: its
      estimated prevalence is between 1/10000 and 1/20000 persons. The severity of
      skeletal and extraskeletal manifestations varies widely. Most patients have a
      mutation in one of the 2 genes that encode the alpha chains of collagen type I.
      Treatment with bisphosphonates has produced clear improvements, especially for
      growing children. The appropriate regimen for bisphosphonate treatment remains to
      be determined: the goal is to find the lowest effective dose to minimize side
      effects. Treatment of osteogenesis imperfecta must be multidisciplinary,
      including physicians, surgeons, and physical therapists.

PMID- 17560762
TI  - [Clinical aspects of Alzheimer disease].
AB  - Alzheimer disease is diagnosed in only half of the patients with this disease in
      France. In its typical form, it is characterized at the onset by short-term
      memory problems, repetitive and unusual oversights and forgetfulness, and
      difficulties in learning new information. Dementia is responsible for more than
      50% of the need for care in the elderly. Disease progression is accompanied by
      noncognitive complications. The 3 most frequent are psychological and behavioral
      symptoms, weight loss, and impaired balance and walking. Its progressive nature
      and potential complications underline the need for multidisciplinary management
      for patients and their families, with regular medical follow-up.

PMID- 17560763
TI  - [Hemochromatosis in the age of genetics].

PMID- 17560764
TI  - Modulation of CYP1A1 and CYP2B1 expression upon cell cycle progression in
      cultures of primary rat hepatocytes.
AB  - Primary cultures of epidermal growth factor (EGF)-stimulated hepatocytes are a
      valuable tool to study the regulation of hepatocyte proliferation. As progression
      through the cell cycle is generally associated with a reduction in liver-specific
      functions, we studied the effects of a proliferative response triggered by EGF on
      the albumin secretion and urea production, and on cytochrome P450 (CYP) 1A1 and
      CYP2B1 expression and their corresponding 7-ethoxyresorufin-O-deethylase (EROD)
      and 7-pentoxyresorufin-O-dealkylase (PROD) activities. It was found that cell
      cycle entry is associated with decreased albumin secretion and urea production.
      Furthermore, western blot analysis revealed that in hepatocytes cultured under
      proliferative conditions, the protein expression of CYP1A1 and CYP2B1 was
      substantially decreased, as well as the CYP2B-mediated PROD activity. In
      contrast, EROD activity was not altered. In addition, the expression levels of
      the liver enriched transcription factors (LETFs) hepatic nuclear factor (HNF)
      3beta and HNF4alpha were downregulated under proliferative conditions, whereas
      the expression of HNF1alpha remained constant. In conclusion, we show that in
      cultured primary hepatocytes, cell cycle progression significantly modulates
      albumin secretion, urea production and CYP-mediated biotransformation, probably
      involving transcriptional regulation by hepatic nuclear factors. Therefore, in
      order to maintain primary hepatocytes functional in culture, cell cycle
      inhibition must be achieved.

PMID- 17560765
TI  - Cytotoxicity induced in myotubes by a Lys49 phospholipase A2 homologue from the
      venom of the snake Bothrops asper: evidence of rapid plasma membrane damage and a
      dual role for extracellular calcium.
AB  - Acute muscle tissue damage, myonecrosis, is a typical consequence of
      envenomations by snakes of the family Viperidae. Catalytically-inactive Lys49
      phospholipase A(2) homologues are abundant myotoxic components in viperid venoms,
      causing plasma membrane damage by a mechanism independent of phospholipid
      hydrolysis. However, the precise mode of action of these myotoxins remains
      unsolved. In this work, a cell culture model of C2C12 myotubes was used to assess
      the action of Bothrops asper myotoxin II (Mt-II), a Lys49 phospholipase A(2)
      homologue. Mt-II induced a dose- and time-dependent cytotoxic effect associated
      with plasma membrane disruption, evidenced by the release of the cytosolic enzyme
      lactate dehydrogenase and the penetration of propidium iodide. A rapid increment
      in cytosolic Ca(2+) occurred after addition of Mt-II. Such elevation was
      associated with hypercontraction of myotubes and blebbing of plasma membrane. An
      increment in the Ca(2+) signal was observed in myotube nuclei. Elimination of
      extracellular Ca(2+) resulted in increased cytotoxicity upon incubation with Mt
      II, suggesting a membrane-protective role for extracellular Ca(2+). Chelation of
      cytosolic Ca(2+) with BAPTA-AM did not modify the cytotoxic effect, probably due
      to the large increment induced by Mt-II in cytosolic Ca(2+) which overrides the
      chelating capacity of BAPTA-AM. It is concluded that Mt-II induces rapid and
      drastic plasma membrane lesion and a prominent Ca(2+) influx in myotubes.
      Extracellular Ca(2+) plays a dual role in this model: it protects the membrane
      from the cytolytic action of the toxin; at the same time, the Ca(2+) influx that
      occurs after membrane disruption is likely to play a key role in the
      intracellular degenerative events associated with Mt-II-induced myotube damage.

PMID- 17560766
TI  - Schizophrenic patients treated with clozapine or olanzapine perform better on
      theory of mind tasks than those treated with risperidone or typical antipsychotic
      medications.
AB  - Theory of mind (ToM), the ability to attribute mental states to others, is
      associated with medial prefrontal cortical (mPFC) activity and is impaired in
      schizophrenia. Olanzapine or clozapine but not typical antipsychotics or
      risperidone preferentially affect c-fos expression in mPFC in animals. We tested
      the hypothesis that schizophrenic patients treated with different antipsychotics
      would perform differently on ToM tasks. Groups receiving Typicals (n=23),
      Clozapine (n=18), Olanzapine (n=20) or Risperidone (n=23) and a Control group of
      healthy volunteers (n=24) were matched for age, gender, handedness and education.
      ToM functioning was assessed with picture sequence, second-order belief and faux
      pas tests. Schizophrenic groups performed similarly to controls on non-ToM
      conditions. The Olanzapine and Clozapine groups performed similarly to Controls
      on ToM tasks. The Typicals and Risperidone groups performed worse than the other
      groups on ToM tasks. We concluded that ToM performance of schizophrenic patients
      is influenced by the antipsychotic they are taking. Our results suggest that
      olanzapine or clozapine but not typicals or risperidone may improve or protect
      ToM ability.

PMID- 17560767
TI  - Sub-chronic phencyclidine administration increases brain-derived neurotrophic
      factor in the RAT hippocampus.

PMID- 17560768
TI  - The effect of doxapram on brain imaging in patients with panic disorder.
AB  - Administration of doxapram hydrochloride, a respiratory stimulant, is experienced
      by panic disorder patients to be similar to panic attacks but has reduced
      emotional effect in normal volunteers, thus providing a laboratory model of panic
      for functional imaging. Six panic patients and seven normal control subjects
      underwent positron emission tomography with (18)F-deoxyglucose imaging after a
      single-blinded administration of either doxapram or a placebo saline solution.
      Saline and doxapram were administered on separate days in counterbalanced order.
      Patients showed a greater heart rate increase on doxapram relative to saline than
      controls, indicating differential response. On the saline placebo day, patients
      had greater prefrontal relative activity than controls. In response to doxapram,
      patients tended to decrease prefrontal activity more than controls, and increased
      cingulate gyrus and amygdala activity more than controls. This suggests that
      panic disorder patients activate frontal inhibitory centers less than controls, a
      tendency that may lower the threshold for panic.

PMID- 17560769
TI  - Growth, biochemical modifications and proline metabolism in Helianthus annuus L.
      as induced by drought stress.
AB  - In the present investigation, two watering treatments, viz., 100% and 60% field
      capacity (FC) were used to understand the effects of water deficit on early
      growth, biomass allocation, pigment and biochemical constituents and proline
      metabolism of five varieties of Sunflower (Helianthus annuus L.) plants. We found
      that there was a significant difference in early growth, dry matter accumulation,
      pigment, biochemical constituents and proline metabolism among the five
      varieties. The root length, shoot length, total leaf area, fresh and dry weight,
      chlorophyll a, b, total chlorophyll and carotenoid were significantly reduced
      under water stress treatments. Water stress increased the proline, free amino
      acid and glycinebetaine contents along with increased activity of gamma-glutamyl
      kinase but the activity of proline oxidase reduced as a consequence of water
      stress.

PMID- 17560770
TI  - Direct apoptotic effects of free fatty acids on human endothelial cells.
AB  - BACKGROUND AND AIM: Endothelial cell injury is a key event in the pathogenesis of
      diabetes-associated atherosclerosis and vascular complications. Increased
      apoptosis may contribute to the loss of endothelial integrity and leads to
      cardiovascular disease. This study was designed to elucidate whether high levels
      of free fatty acids (FFA) cause apoptosis and if so what is the possible role of
      insulin signaling alteration(s) in determining this effect. METHODS AND RESULTS:
      In human umbilical vein endothelial cells (HUVECs) cultured for 72h with high
      levels of FFA, apoptotic cells, detected by Annexin V-FITC and PI, were
      increased. Then we observed a decrease of Bcl-2/Bax ratio (pro-apoptotic
      condition), measured by RT-PCR and Western blot. As the Akt pathway is involved
      in insulin signaling and apoptosis, we investigated whether Akt mediated FFA
      apoptotic effects. HUVECs exposed to FFA showed an equal amount of total Akt
      protein content compared to controls. In HUVECs, FFA induced a significant
      decrease in phosphorylated active Akt. Furthermore, phosphorylated eNOS (active
      form) was decreased and cleaved caspase-9 (active form) was increased. These
      alterations were prevented when insulin at 10(-8)M was added in culture medium
      containing FFA. The insulin anti-apoptotic effect was prevented by Ly29400, a
      PI3K/Akt inhibitor. CONCLUSION: High levels of FFA cause HUVECs apoptosis through
      Akt inhibition; insulin can prevent these effects. Inappropriate FFA elevation
      may affect vascular endothelium by impairing cell survival via activation of
      apoptosis, thus contributing to the development of cardiovascular disease in type
      2 diabetic patients.

PMID- 17560771
TI  - Low serum testosterone in men is inversely associated with non-fasting serum
      triglycerides: the Tromso study.
AB  - OBJECTIVE: To study the relationships between endogenous testosterone, sex
      hormone-binding globulin (SHBG) and serum lipids in non-fasting men. METHODS: We
      performed a cross-sectional study in 1274 men without known cardiovascular
      disease who participated in a population-based study, the 1994/1995 Tromso study.
      Anthropometric characteristics were measured and questionnaires regarding
      lifestyle and medical history were completed. Non-fasting blood samples were
      drawn between 08.00 and 16.00h, and total testosterone, SHBG, triglycerides (TG),
      total cholesterol (TC) and high-density lipoprotein (HDL) were analyzed. RESULTS:
      In stratified analyses based on sampling time, a linear increase in serum TG
      levels was found in men with total testosterone levels below the 50th percentile
      during the day (p for trend=0.004). In contrast, serum triglycerides did not
      change during the day in men with testosterone levels above the 50th percentile.
      In regression analyses, total testosterone and SHBG were inversely and
      independently associated with TG (p<0.001 and p<0.001 respectively), and
      positively and independently associated with HDL (p=0.005 and p<0.001,
      respectively). Men with an unfavorable lipid profile (HDL <0.90 and TG >1.8) had
      significantly lower levels of total testosterone and SHBG (p=0.004 and p<0.001,
      respectively) in age and BMI adjusted analyses, compared to men with a normal
      lipid profile. CONCLUSIONS: Low serum total testosterone was associated with a
      linear increase in serum TG during the day, and was independently associated with
      an unfavorable lipid profile. Our findings may indicate that low total
      testosterone is associated with impaired TG metabolism in men.

PMID- 17560772
TI  - Chitosan-based spray-dried respirable powders for sustained delivery of
      terbutaline sulfate.
AB  - In this study, we describe the preparation of highly dispersible dry powders for
      pulmonary drug delivery that display sustained drug release characteristics.
      Powders were prepared by spray-drying 30% v/v aqueous ethanol formulations
      containing terbutaline sulfate as a model drug, chitosan as a drug release
      modifier and leucine as an aerosolisation enhancer. The influence of chitosan
      molecular weight on the drug release profile was investigated by using low,
      medium and high molecular weight chitosan or combinations thereof. Following
      spray-drying, resultant powders were characterised using scanning electron
      microscopy, laser diffraction, tapped density analysis, differential scanning
      calorimetry and thermogravitational analysis. The in vitro aerosolisation
      performance and drug release profile were investigated using Multi-Stage Liquid
      Impinger analysis and modified USP II dissolution apparatus, respectively. The
      powders generated were of a suitable aerodynamic size for inhalation, had low
      moisture content and were amorphous in nature. The powders were highly
      dispersible, with emitted doses of over 90% and fine particle fractions of up to
      82% of the total loaded dose, and mass median aerodynamic diameters of less than
      2.5microm. A sustained drug release profile was observed during dissolution
      testing; increasing the molecular weight of the chitosan in the formulation
      increased the duration of drug release.

PMID- 17560773
TI  - Re: pulmonary tumor types induced in Wistar rats of the so-called "19-dust
      study".

PMID- 17560774
TI  - Differences between the data bases, statistical analyses, and interpretations of
      lung tumors of the 19-dust study: two controversial views.
AB  - The article presents a comparison of two opposing evaluations and interpretations
      of the carcinogenicity study with 19 granular dusts. It is one of the two
      responses to a Letter to the Editor of Exp Toxicol Pathol by Morfeld and Borm(1),
      who had analysed selected data from the primary source of our study [Borm et al.,
      Inhal Toxicol 2000;12(Suppl 3):225-31; Borm et al., Int J Cancer 2004;110:3-14;
      Morfeld et al., Inhal Toxicol 2006:18:215-25]. In contrast, our statistical
      analyses are based on the authentic and complete results of the study published
      with a detailed description of materials, methods and results [Pott and Roller,
      Eur J Oncol 2005,10:249-81; Mohr et al. Exp Toxicol Pathol 2006;58:13-20; Roller
      and Pott, Ann NY Acad Sci 2006,1076:266-80]. Analysis of the tumor incidences
      from non-specifically toxic dusts in terms of a usual multistage model leads to
      reasonable dose-response curves and to the finding that tumor risk depends on the
      retained dust volume and on mean particle size. The model is adequate because
      survival of the groups included in the analysis was not reduced. In contrast to
      this analysis, Morfeld et al. (2006) calculated an implausible threshold of 10mg
      instilled total dust per rat and a saturation dose of 20mg. These values are not
      compatible with the data because three dose groups with highly significantly
      increased tumor incidences (up to 67%) lie within the 95% confidence interval of
      the threshold dose of Morfeld et al. (2006). The claim of Morfeld [Zbl Arbeitsmed
      2004;54(7):246-58] to consider as "of interest" only carcinogenicity tests with
      doses similar to current occupational exposure limit values would make it
      impossible to identify the carcinogenicity of non-specifically toxic dusts even
      if the excess risk is higher than 1 in 100.

PMID- 17560776
TI  - Realising resource efficiency in the management of healthcare waste from the
      Cornwall National Health Service (NHS) in the UK.
AB  - The quantities of waste generated by the healthcare sector in the United Kingdom
      (UK) have been shown to be amongst the highest in Europe. Based on a case study
      undertaken within the Cornwall NHS (National Health Service) in the UK, this
      paper reports on the results of waste minimisation trials. The schemes were able
      to achieve significant waste reductions in both clinical and domestic waste
      quantities. Indeed, a reduction in domestic bag waste in the range of 1.6-33.4%,
      with an average of 14.8% was realised. For clinical waste, the reduction ranged
      from 1.8% to 38.3%, at an average of 15.7%, with net cost benefits of nearly US$
      25,000 over the period of 1-3 years. The outcomes suggest that significant
      resource and financial efficiencies can be attained, but due to the many factors
      involved, there is a need to focus both on containment and logistics, as well as
      social factors for success.

PMID- 17560777
TI  - Single-cell-based sensors and synchrotron FTIR spectroscopy: a hybrid system
      towards bacterial detection.
AB  - Microarrays of single macrophage cell-based sensors were developed and
      demonstrated for potential real-time bacterium detection by synchrotron FTIR
      microscopy. The cells were patterned on gold electrodes of silicon oxide
      substrates by a surface engineering technique, in which the gold electrodes were
      immobilized with fibronectin to mediate cell adhesion and the silicon oxide
      background was passivated with polyethylene glycol (PEG) to resist protein
      adsorption and cell adhesion. Cell morphology and IR spectra of single, double,
      and triple cells on gold electrodes exposed to lipopolysaccharide (LPS) of
      different concentrations were compared to reveal the detection capability of this
      cell-based sensing platform. The single-cell-based system was found to generate
      the most significant and consistent IR spectrum shifts upon exposure to LPS, thus
      providing the highest detection sensitivity. Changes in cell morphology and IR
      shifts upon cell exposure to LPS were found to be dependent on the LPS
      concentration and exposure time, which established a method for the
      identification of LPS concentration and infected cell population. Possibility of
      using this single-cell system with conventional IR spectroscopy as well as its
      limitation was investigated by comparing IR spectra of single-cell arrays with
      gold electrode surface areas of 25, 100, and 400 microm2 using both synchrotron
      and conventional FTIR spectromicroscopes. This cell-based platform may
      potentially provide real-time, label-free, and rapid bacterial detection, and
      allow for high-throughput statistical analyses, and portability.

PMID- 17560775
TI  - The bone morphogenetic protein 1/Tolloid-like metalloproteinases.
AB  - A decade ago, bone morphogenetic protein 1 (BMP1) was shown to provide the
      activity necessary for proteolytic removal of the C-propeptides of procollagens I
      III: precursors of the major fibrillar collagens. Subsequent studies have shown
      BMP1 to be the prototype of a small group of extracellular metalloproteinases
      that play manifold roles in regulating formation of the extracellular matrix
      (ECM). Soon after initial cloning of BMP1, genetic studies showed the related
      Drosophila proteinase Tolloid (TLD) to be necessary for the formation of the
      dorsal-ventral axis in early embryogenesis. It is now clear that the BMP1/TLD
      like proteinases, conserved in species ranging from Drosophila to humans, act in
      dorsal-ventral patterning via activation of transforming growth factor beta
      (TGFbeta)-like proteins BMP2, BMP4 (vertebrates) and decapentaplegic
      (arthropods). More recently, it has become apparent that the BMP1/TLD-like
      proteinases are activators of a broader subset of the TGFbeta superfamily of
      proteins, with implications that these proteinases may be key in orchestrating
      the formation of ECM with growth factor activation and BMP signaling in
      morphogenetic processes.

PMID- 17560778
TI  - Controlling the surface density of DNA on gold by electrically induced
      desorption.
AB  - We report on a method to control the packing density of sulfur-bound
      oligonucleotide layers on metal electrodes by electrical means. In a first step,
      a dense nucleic acid layer is deposited by self-assembly from solution; in a
      second step, defined fractions of DNA molecules are released from the surface by
      applying a series of negative voltage cycles. Systematic investigations of the
      influence of the applied electrode potentials and oligonucleotide length allow us
      to identify a sharp desorption onset at -0.65 V versus Ag/AgCl, which is
      independent of the DNA length. Moreover, our results clearly show the pronounced
      influence of competitive adsorbents in solution on the desorption behavior, which
      can prevent the re-adsorption of released DNA molecules, thereby enhancing the
      desorption efficiency. The method is fully bio-compatible and can be employed to
      improve the functionality of DNA layers. This is demonstrated in hybridization
      experiments revealing almost perfect yields for electrically "diluted" DNA
      layers. The proposed control method is extremely beneficial to the field of DNA
      based sensors.

PMID- 17560779
TI  - Assessment of the interaction between a synthetic epitope of troponin C and its
      specific antibody using a label-free faradaic impedimetric immunosensor and alpha
      Keggin silicotungstic heteropolyacid as a redox probe.
AB  - The development of an immunosensor for the direct probing of the interaction
      between a cysteine-modified synthetic peptide, which corresponds to the epitope
      cTnC-89-98 of troponin C, and its specific antibody is described. Following
      immobilization of the peptide onto gold electrodes through the formation of a
      self-assembled monolayer, the alteration of the interfacial properties of the
      electrodes upon peptide-antibody interaction was traced by faradaic
      electrochemical impedance spectroscopy (EIS) using a silicotungstic
      heteropolyacid, H(4)SiO(4).12WO(3), as a redox probe. The electrochemical
      behaviour of the redox probe was evaluated with cyclic voltammetry and EIS. The
      effect of milk protein or 4-mercaptophenol, which was used as post-blocking
      agents, on the performance of the immunosensor, was investigated. Treatment with
      4-mercaptophenol resulted in immunoeffective electrodes that successfully tested
      in anti-serum samples. An optimum dilution ratio of the samples, where the effect
      of the matrix on the measuring signal is negligible, was also determined.

PMID- 17560780
TI  - Arsenic removal in an iron oxide-coated fungal biomass column: analysis of
      breakthrough curves.
AB  - Column studies were conducted, using iron oxide-coated Aspergillus niger biomass,
      to examine the removal of arsenic [As(III) and As(V)] from an aqueous solution.
      The Thomas and Yan models were examined to predict the breakthrough curves. The
      Yan Model described the data better (based on the R(2) values) when compared with
      the Thomas Model. The adsorption capacity of the iron oxide-coated biomass
      estimated by the Thomas Model {1070 microg/g for As(V) and 700 microg/g for
      As(III)} was comparable to the calculated value of its adsorption capacity {1080
      microg/g for As(V) and 880 microg/g for As(III)}.

PMID- 17560781
TI  - An experimental study of vermi-biowaste composting for agricultural soil
      improvement.
AB  - Vermitechnology was investigated as a means of reducing organic waste materials.
      Vermicomposting conditions were optimized to convert the biowastes to nutritious
      composts for amending agricultural soil. Studies were undertaken to select the
      most suitable earthworm species for vermicomposting, to enrich vermicompost by
      inoculation with beneficial microbes, to standardize an economically feasible
      method of vermicomposting, to achieve nutrient economy through vermicompost
      application in acid soils (pH 4.5), and to assess the performance of vermicompost
      as a bioinoculant in cow-pea, banana, and cassava. Earthworm species Eudrillus
      eugineae, Eisenia foetida, Perionyx sansibaricus, Pontoscolex corethrurus and
      Megascolex chinensis were compared for their efficiencies in biodegrading organic
      wastes. E. eugineae was found to be a superb agent. As a bioinoculant,
      vermicompost increased nitrogen and phosphorous availability by enhancing
      biological nitrogen fixation and phosphorous solubilisation. Vermicompost-amended
      acid-agriculture-soil significantly improved the yield, biometric character and
      quality of banana, cassava and cow-pea. Vermicompost application stimulated root
      growth, facilitating nutrient absorption and thereby favouring higher yield.

PMID- 17560782
TI  - A new approach to modification of natural adsorbent for heavy metal adsorption.
AB  - This paper describes modification of a natural adsorbent with Fenton reagent and
      determines the removal of Cd(II) ions from aqueous solution. Changes of the
      surface properties of adsorbent materials were determined by the FT-IR analysis
      after the modification of pine bark. The effect of Fe2+/H2O2 ratio, ORP, pH, and
      contact time were determined. Different adsorption isotherms were also obtained
      using concentrations of Cd(II) ions ranging from 0.1 to 100 mg L(-1). The
      adsorption process follows pseudo-first-order reaction kinetics and follows the
      Langmuir adsorption isotherm. The paper discusses thermodynamic parameters,
      including changes in Gibbs free energy, entropy, and enthalpy, for the adsorption
      of Cd(II) on modified bark, and revealed that the adsorption process was
      spontaneous and exothermic under natural conditions. The maximum removal
      efficiency obtained was 97% at pH 7 and with a 90-min contact time (for 35 mg L(
      1) initial concentration and a 2.5 g L(-1) solid-to-liquid ratio).

PMID- 17560783
TI  - Synthesis and in vitro activity of 2-thiazolylhydrazone derivatives compared with
      the activity of clotrimazole against clinical isolates of Candida spp.
AB  - In this paper, we report on the synthesis of a novel series of 2
      thiazolylhydrazone derivatives and the influence of the substituents on the
      thiazole ring on antifungal activity. All synthesized compounds were screened for
      their in vitro activities against 22 clinical isolates of Candida spp.,
      representing six different species, compared to clotrimazole as a reference
      compound. Some of the tested compounds were found to possess significant
      antifungal activity when compared to clotrimazole, in particular compound 14
      which exhibited higher potency against most of the Candida spp. considered. The
      compounds that were most active as anti-Candida agents were also submitted to
      cytotoxic screening by the Trypan Blue dye exclusion assay and in general they
      were shown to induce low cytotoxic effects.

PMID- 17560784
TI  - Selective oxidation of sulfides to sulfoxides catalyzed by ruthenium (III) meso
      tetraphenylporphyrin chloride in the presence of molecular oxygen.
AB  - Highly efficient selective oxidation of sulfides to sulfoxides by molecular
      oxygen catalyzed by ruthenium (III) meso-tetraphenylporphyrin chloride
      (Ru(TPP)Cl) with isobutyraldehyde as oxygen acceptor has been reported. In large
      scale experiment of thioanisole oxidation, the isolated yield of sulfoxide of 92%
      was obtained and the turnover number reached up to 92,000.

PMID- 17560785
TI  - Design of a partial PPARdelta agonist.
AB  - Structure based ligand design was used in order to design a partial agonist for
      the PPARdelta receptor. The maximum activation in the transactivation assay was
      reduced from 87% to 39%. The crystal structure of the ligand binding domain of
      the PPARdelta receptor in complex with compound 2 was determined in order to
      understand the structural changes which gave rise to the decrease in maximum
      activation.

PMID- 17560786
TI  - Synthesis and evaluation of potent and selective beta3 adrenergic receptor
      agonists containing heterobiaryl carboxylic acids.
AB  - The design, synthesis, and SAR of a novel series of heterobiaryl phenethanolamine
      beta3 adrenergic receptor agonists are described. The furan analogue 49 was shown
      to elicit a significant dose-dependent lowering of plasma glucose in a rodent
      model of type 2 diabetes.

PMID- 17560787
TI  - The 577X allele of the ACTN3 gene is associated with improved exercise capacity
      in women with McArdle's disease.
AB  - We assessed the possible association existing between alpha-actinin-3 (ACTN3)
      R577X genotypes and the capacity for performing aerobic exercise in McArdle's
      patients. Forty adult McArdle's disease patients and forty healthy, age and
      gender-matched sedentary controls (21 men, 19 women in both groups) performed a
      graded test until exhaustion and a constant-load test on a cycle-ergometer to
      determine clinically relevant indices of exercise capacity as peak oxygen uptake
      (VO(2peak)) and the ventilatory threshold (VT). In the group of diseased women,
      carriers of the X allele had a higher (P<0.01) VO(2peak) (15.0+/-1.2 ml/kg/min)
      and a higher (P<0.05) oxygen uptake (VO(2)) at the VT (11.2+/-1 ml/kg/min) than
      R/R homozygotes (VO(2peak): 9.6+/-0.5 ml/kg/min; VO(2) at the VT: 8.2+/-0.7
      ml/kg/min). No differences were found in male patients. In women with McArdle's
      disease, ACTN3 genotypes might partly explain the large individual variability
      that exists in the phenotypic manifestation of this disorder.

PMID- 17560788
TI  - Discovery of pyrrole-based hepatoselective ligands as potent inhibitors of HMG
      CoA reductase.
AB  - In an effort to identify hepatoselective inhibitors of HMG-CoA reductase, two
      series of pyrroles were synthesized and evaluated. Efforts were made to modify
      (3R,5R)-7-[3-(4-fluorophenyl)-1-isopropyl-4-phenyl-5-phenylcarbamoyl-1H-pyrrol-2
      yl]-3,5-dihydroxy-heptanoic acid sodium salt 30 in order to reduce its
      lipophilicity and therefore increase hepatoselectivity. Two strategies that were
      explored were replacement of the lipophilic 3-phenyl substituent with either a
      polar function (pyridyl series) or with lower alkyl substituents (lower alkyl
      series) and attachment of additional polar moieties at the 2-position of the
      pyrrole ring. One compound was identified to be both highly hepatoselective and
      active in vivo. We report the discovery, synthesis, and optimization of
      substituted pyrrole-based hepatoselective ligands as potent inhibitors of HMG-CoA
      reductase for reducing low density lipoprotein cholesterol (LDL-c) in the
      treatment of hypercholesterolemia.

PMID- 17560789
TI  - Visualization of mitotic HeLa cells by advanced polarized light microscopy.
AB  - The conventional polarized light imaging system can observe sub-microscopic
      molecular order non-destructively, quantitatively and without labeling or
      staining. Recently, a more sophisticated version, Abrio imaging system, than the
      conventional polarized light imaging system, was developed. This advanced
      polarized light imaging system has simplified the process of birefringent
      imaging, higher sensitivity and accuracy irrespective of sample orientation. By
      performing time-lapse observations using the advanced polarized light microscopy,
      we visualized mitotic spindles, especially kinetochore microtubules, of HeLa
      cells. Moreover, we successfully visualized the detailed structure of several
      filament bundles, which possibly are components of the contractile ring. Here, we
      report the potential of advanced polarized light imaging systems for imaging
      mitotic HeLa cells and the new insights obtained during this microscopic study.

PMID- 17560790
TI  - Increased vulnerability of nigrostriatal terminals in DJ-1-deficient mice is
      mediated by the dopamine transporter.
AB  - Mutations in the gene for DJ-1 have been associated with early-onset autosomal
      recessive parkinsonism. Previous studies of null DJ-1 mice have shown alterations
      in striatal dopamine (DA) transmission with no DAergic cell loss. Here we
      characterize a new line of DJ-1-deficient mice. A subtle locomotor deficit was
      present in the absence of a change in striatal DA levels. However, increased
      [(3)H]-DA synaptosomal uptake and [(125)I]-RTI-121 binding were measured in null
      DJ-1 vs. wild-type mice. Western analyses of synaptosomes revealed significantly
      higher dopamine transporter (DAT) levels in pre-synaptic membrane fractions. 1
      Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) exposure exacerbated striatal
      DA depletion in null DJ-1 mice with no difference in DAergic nigral cell loss.
      Furthermore, increased 1-methyl-4-phenylpyridinium (MPP(+)) synaptosomal uptake
      and enhanced MPP(+) accumulation were measured in DJ-1-deficient vs. control
      striatum. Thus, under null DJ-1 conditions, DAT changes likely contribute to
      altered DA neurotransmission and enhanced sensitivity to toxins that utilize DAT
      for nigrostriatal entry.

PMID- 17560791
TI  - Pathological activity of familial Alzheimer's disease-associated mutant
      presenilin can be executed by six different gamma-secretase complexes.
AB  - gamma-Secretase is a protease complex, which catalyzes the final of two
      subsequent cleavages of the beta-amyloid precursor protein (APP) to release the
      amyloid-beta peptide (Abeta) implicated in Alzheimer's disease (AD) pathogenesis.
      In human cells, six gamma-secretase complexes exist, which are composed of either
      presenilin (PS) 1 or 2, the catalytic subunit, nicastrin, PEN-2, and either APH
      1a (as S or L splice variants) or its homolog APH-1b. It is not known whether and
      how different APH-1 species contribute to the pathogenic activity of gamma
      secretase complexes with familial AD (FAD)-associated mutant PS. Here we show
      that all known gamma-secretase complexes are active in APP processing and that
      all combinations of APH-1 variants with either FAD mutant PS1 or PS2 support
      pathogenic Abeta(42) production. Since our data suggest that pathogenic gamma
      secretase activity cannot be attributed to a discrete gamma-secretase complex, we
      propose that all gamma-secretase complexes have to be explored and evaluated for
      their potential as AD drug target.

PMID- 17560792
TI  - Effect of the TAT-RasGAP(317-326) peptide on apoptosis of human malignant
      mesothelioma cells and fibroblasts exposed to meso-tetra-hydroxyphenyl-chlorin
      and light.
AB  - BACKGROUND: 5,10,15,20-Tetrakis(m-hydroxyphenyl)chlorin (mTHPC)-mediated
      photodynamic therapy (PDT) has shown insufficient tumor selectivity for the
      treatment of pleural mesothelioma. Tumor selectivity of mTHPC-PDT may be enhanced
      in the presence of the TAT-RasGAP(317-326) peptide which has the potential to
      specifically sensitize tumor cells to cytostatic agents. MATERIALS AND METHODS: H
      meso-1 and human fibroblast cell cultures, respectively, were exposed to two
      different mTHPC doses followed by light delivery with and without TAT-RasGAP(317
      326) administration. mTHPC was added to the cultures at a concentration of
      0.04microg/ml and 0.10microg/ml, respectively, 24h before laser light
      illumination at 652nm (3J/cm(2), 40mW/cm(2)). TAT-RasGAP(317-326) was added to
      the cultures immediately after light delivery at a concentration of 20microM. The
      apoptosis rate was determined by scoring the cells displaying pycnotic nuclei.
      Cell viability was measured by using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl
      tetrazolium bromide (MTT) assay. RESULTS: Light delivery associated with
      0.04microg/ml mTHPC resulted in a significantly higher apoptosis rate in the
      presence of TAT-RasGAP(317-326) than without in H-meso-1 cells (p<0.05) but not
      in fibroblasts. In contrast, 1.0microg/ml mTHPC and light resulted in a
      significantly higher apoptosis rate in both H-meso-1 cells and fibroblasts as
      compared to controls (p<0.05) but the addition of TAT-RasGAP(317-326) did not
      lead to a further significant increase of the apoptosis rate of both H-meso-1
      cells and fibroblasts as compared to mTHPC and light delivery alone. CONCLUSION:
      TAT-RasGAP(317-326) selectively enhanced the effect of mTHPC and light delivery
      on H-meso-1 cells but not on fibroblasts. However, this effect was mTHPC dose
      dependent and occurred only at a low sensitizer dose.

PMID- 17560793
TI  - The oxidation/reduction kinetics of the plastoquinone pool controls the
      appearance of the I-peak in the O-J-I-P chlorophyll fluorescence rise: effects of
      various electron acceptors.
AB  - Quantitative analysis of the fluorescence induction (FI) rise was used in this
      study to elucidate the complex effects of N,N,N',N'-tetramethyl-p
      phenylenediamine (TMPD) on thylakoids. Reduced TMPD molecules, responsible for
      the ADRY agent effect, caused an increase in the amplitude of the O-J rise. Also,
      only oxidized TMPD molecules were shown to have the ability to bind the Q(B)
      pocket of photosystem II (PSII). On the other hand, the I-P rise was slowed in
      proportion with the oxidized TMPD concentration, inducing the clear appearance of
      the I-peak. While this property was previously thought to be unique to TMPD, this
      study shows that some artificial electron acceptors of PSII, silicomolybdate, 2,5
      dichloro-p-benzoquinone, and phenyl-p-benzoquinone, have a similar effect. These
      results demonstrated a major role of the oxido-reduction kinetics of the PQ-pool
      in the resolution of J-I and I-P phases in the FI of isolated thylakoids.

PMID- 17560794
TI  - Working memory and syntax interact in Broca's area.
AB  - Comprehension of filler-gap dependency relations (as in this is the man who the
      woman is touching) is supported by Broca's area. There are two views regarding
      the processing role of this brain region in comprehending these dependencies.
      Specifists hold that Broca's area plays a specific syntactic role in processing
      filler-gaps. Generalists maintain that as the on-line linking of fillers and gaps
      taxes Working Memory (WM) resources, Broca's area supports a domain general WM.
      The current fMRI study tested these two views in a grammaticality judgment task,
      where participants were presented with two syntactically distinct dependency
      relations: (a) Filler-Gap and (b) Reflexive Binding. The distance between the
      dependent elements within each of the constructions was varied, to parametrically
      vary WM demands. The Generalists would expect parametric variation of distance in
      both dependencies to lead to a linear increase in activation of Broca's area. Our
      results support the specifists' view, however: the left inferior frontal gyrus
      demonstrated an interaction between distance and dependency type with a positive
      linear effect only for Filler-Gaps. A positive linear effect of distance across
      both dependencies was only found in the bilateral parahippocampal/fusiform gyri.
      Therefore the role of Broca's area in WM is syntactically specific to filler-gap
      relations.

PMID- 17560795
TI  - A neonatal atlas template for spatial normalization of whole-brain magnetic
      resonance images of newborns: preliminary results.
AB  - Commonly used brain templates are based on adults' or children's brains. In this
      study, we create a neonatal brain template. This becomes necessary because of the
      pronounced differences not only in size but even more importantly in geometrical
      proportions of the brains of adults and children as compared to the ones of
      newborns. The template is created based on high resolution T1 magnetic resonance
      images of 7 individuals with gestational ages between 39 and 42 weeks at the
      dates of examination. As usual, the created template presents two characteristics
      in a single image: an average intensity and an average shape. The normalization
      process to map subjects to the same space is done using SPM2 (Statistical
      Parametric Mapping) and its deformation toolbox. It consists of two steps: an
      affine and a nonlinear registration for global and local alignments,
      respectively. The template was evaluated by (i) study of anatomical local
      deviations and (ii) amount of local deformations of brain tissues in normalized
      neonatal images. The extracted results were compared with the ones obtained by
      normalization using adult and pediatric templates. It was shown that the
      application of our neonatal brain template for alignment of neonatal images
      results in a pronounced increase in performance of the normalization procedure as
      indicated by reduction of deviation of anatomical equivalent structures. The
      neonatal atlas template is freely downloadable from http://www.u
      picardie.fr/labo/GRAMFC.

PMID- 17560796
TI  - Hippocampal event-related potentials to tone duration deviance in a passive
      oddball paradigm in humans.
AB  - The mismatch negativity (MMN), a component of event-related potentials (ERPs), is
      assumed to reflect a preattentive auditory discrimination process. Although an
      involvement of hippocampal structures in deviance detection was shown in animal
      experiments, invasive recordings in humans have not been able to provide such an
      evidence so far. In the current study, ERPs were recorded from intrahippocampal
      and scalp electrodes in 16 epilepsy patients. Stimulation consisted of trains of
      six tones, with one tone deviating in duration (100 vs. 50 ms). In the rhinal
      cortex, ERPs elicited by deviants were larger in amplitude than those of
      standards (around 200 ms). The rhinal activation was succeeded by a long-lasting
      hippocampal ERP component (around 350 ms). However, in contrast to the rhinal
      activation, hippocampal activation was also elicited by the 1st stimuli of the
      train and might, therefore, be related more to salience detection than to
      deviance detection. The current study provides evidence that the MMN is part of a
      multistage comparison process and that the rhinal cortex is part of its
      underlying cortical network.

PMID- 17560797
TI  - Progressive atrophy in the optic pathway and visual cortex of early blind Chinese
      adults: A voxel-based morphometry magnetic resonance imaging study.
AB  - Many previous neuroimaging studies have shown that the early visual cortex of the
      early blind (EB) exhibits significant functional plasticity. However, only few
      previous studies have addressed the question whether or not such functional
      plasticity is accompanied by, and even related to, structural plasticity. In this
      study, we acquired high-resolution whole-brain anatomical magnetic resonance
      images form 14 Chinese EB adults, who lost sight before 6 years of age, and 16
      age/gender-matched normal-sighted controls (SC), and compared pixel-by-pixel the
      gray matter (GM) and white matter (WM) volumes between the two groups with voxel
      based morphometry. The results showed that, relative to the SC, the EB exhibits
      significantly reduced WM volumes in the optic tract and optic radiation and
      significant GM losses in the early visual cortex. The reduction of WM volume in
      the optic radiation of the EB was found be modulated by both the age at blindness
      onset and the duration of blindness. The reduction of GM volume in the early
      visual cortex of the EB appeared to be unaffected by the age at blindness onset.
      However, it was found in localized regions of the atrophic early visual cortex of
      the EB that the GM loss was progressive with aging and increasing duration of
      blindness. These results suggest that early visual deprivation induces
      significant structural plasticity in the optic pathway and early visual cortex of
      the EB, which likely occurs during both the critical period of early
      neurodevelopment and the course of persisted blindness later in life through
      activity-dependent mechanisms.

PMID- 17560798
TI  - Novel method for visualizing and modeling the spatial distribution of neural stem
      cells within intracranial glioma.
AB  - Neural stem cells (NSCs) hold great promise for glioma therapy due to their
      inherent tumor-tropic properties, enabling them to deliver therapeutic agents
      directly to invasive tumor sites. In the present study, we visualized and
      quantitatively analyzed the spatial distribution of tumor-tropic NSCs in a mouse
      model of orthotopic glioma in order to predict the therapeutic efficacy of a
      representative NSC-based glioma therapy. U251.eGFP human glioma was established
      in the brain of athymic mice, followed by stereotactic injection of CM-DiI
      labeled human NSCs posterior-lateral to the tumor site. Confocal microscopy,
      three-dimensional modeling and mathematical algorithms were used to visualize and
      characterize the spatial distribution of NSCs throughout the tumor. The pattern
      of NSC distribution showed a gradient with higher densities toward the centroid
      of the tumor mass. We estimate that NSC-mediated therapy would eradicate 70-90%
      of the primary tumor mass and the majority of invasive tumor foci. Our method may
      serve as a model for optimizing the efficacy of NSC-based glioma therapy.

PMID- 17560799
TI  - The evaluation for generic-level monophyly of Ancyrocephalinae (Monogenea,
      Dactylogyridae) using ribosomal DNA sequence data.
AB  - To overcome the limited regional and taxonomic coverage in previous studies of
      the Ancyrocephalinae (Monogenea, Dactylogyridae), we present further findings on
      the molecular systematics and phylogeny of a broader selection of specimens,
      aiming to build a molecular phylogeny of the Ancyrocephalinae, and to assess the
      monophyly of each available genus, using D1-D2 domain of LSU rDNA and the
      combined LSU and partial sequence of SSU rDNA data sets. Our studies showed that
      18 Haliotrema species were highly dispersive to form several clades with species
      from ten closely related genera. The host range of Euryhaliotrematoides species
      was not only restricted in butterfly fishes (Chaetodontidae), but widen to
      include the Lutjanidae. Euryhaliotrema was phylogenetically more closely related
      to Aliatrema than to Euryhaliotrematoides. Given that the species Haliotrema
      kurodai, Haliotrema spirotubiforum and Haliotrema anguiformis had a funnel-shaped
      base of the coiled male copulatory organ (MCO) lacking an accessory piece, and
      our molecular evidence, we proposed to transfer the three species to the
      Aliatrema as new combinations. We proposed to combine Bravohollisia and
      Caballeria into one genus, mainly based on molecular evidence and their similar
      MCO characters. Using SSU+ITS1 data set, Scutogyrus was robustly resolved as a
      polyphyletic group and its status should be questioned. Based on the present
      molecular evidence and their similar MCO characters, we proposed to combine
      Cichlidogyrus and Scutogyrus into one genus, Cichlidogyrus, by treating
      Scutogyrus as the synonym of Cichlidogyrus. Generally, the present study
      indicated that the vagina can make little contribution for understanding the
      generic-level monophyly, due to its high variability even among phylogenetically
      very closely related species, but it was useful for species determination. Given
      that phylogenetically closely related species from the same or closely related
      host species may have similar MCO characters but distinct haptoral characters, we
      consider that it is dangerous to erect a genus mainly based on different haptoral
      characters, particularly those separated from existing genera. The resultant
      phylogenetic reconstructions indicated that the radiation of some Haliotrema
      species has correlated with their hosts, because species from closely related
      fishes have correspondingly shown close relationships. Though the present study
      can not provide the comparison of host-parasite associations, phylogenetically
      closely related Haliotrema species which have similar morphological characters
      (both MCOs and haptors) but distinct/distantly related host species may indicate
      a speciation model of host-switching.

PMID- 17560800
TI  - Phylogeny of benthic Phyllodocidae (Polychaeta) based on morphological and
      molecular data.
AB  - A combined molecular (18S rDNA, 28S rDNA, 16S rDNA and COI) and morphological
      analysis of the benthic phyllodocids is presented for the first time. Nineteen
      phyllodocids and two outgroup taxa are assessed using parsimony, maximum
      likelihood and Bayesian analyses. We demonstrate high degrees in homoplasy in the
      traditionally used morphological phyllodocid characters, and show that all the
      three current subfamilies Phyllodocinae, Eteoninae and Notophyllinae are non
      monophyletic. The genera Eulalia, Eumida, Protomystides, Pseudomystides,
      Pterocirrus and Sige form a well-supported group, as does Mystides and
      Nereiphylla. Another clade with strong support includes Eteone and Paranaitis,
      although with Eteone nested within a paraphyletic Paranaitis. The relationship
      between these two taxa indicate that the unusual arrangement of modified cirri on
      the first segments in Eteone is due to a fusion of segment 1 and 2 where the
      cirri of segment 1 have been reduced. Eulalia is non-monophyletic and should be
      split, minimally into two groups. Our results are ambiguous regarding the
      ancestral phyllodocid condition of absence-presence of median antenna or nuchal
      papilla and uniramous or biramous parapodia, but shows that the absence of cirri
      on segment 3 (previously an apomorphy, for e.g., Mystides, Pseudomystides and
      Hesionura) is maximally homoplastic.

PMID- 17560801
TI  - Colonization of and radiation in South America by butterflies in the subtribe
      Phyciodina (Lepidoptera: Nymphalidae).
AB  - The historical biogeography of insects in South America is largely unknown, as
      dated phylogenies have not been available for most groups. We have studied the
      phylogenetic relationships and historical biogeography of a subtribe of
      butterflies, Phyciodina in the family Nymphalidae, based on one mitochondrial
      gene (COI) and two nuclear gene regions (EF-1alpha and wingless). The subtribe
      comprises 89 species mainly found in tropical South America, with a few species
      in North America and the Greater Antilles. We find that the enigmatic genus
      Antillea is sister to the rest of Phyciodina, and suggest that it should be
      included in the subtribe. Several genera are found to be polyphyletic or nested
      within another genus, and are proposed to be synonymised. These are Dagon,
      Castilia, Telenassa and Janatella, which we propose should be synonymised with
      Eresia. Brazilian "Ortilia" form an independent lineage and require a new genus
      name. The diversification of Phyciodina has probably taken place over the past
      about 34 MYA. The ancestral phyciodine colonised South America from North America
      through a possible landspan that connected the Greater Antilles to South America
      about 34MYA. A vicariance event left the ancestral Antillea on the Greater
      Antilles, while the ancestral 0e on South America colonised the Guyanan Shield
      and soon after the Brazilian Shield. We hypothesise that the Brazilian Shield was
      an important area for the diversification of Phyciodina. From there, the ancestor
      of Anthanassa, Eresia and Tegosa colonised NW South America, where especially
      Eresia diversified in concert with the rising of the Andes beginning about 20
      MYA. Central America was colonised from NW South America about 15 MYA by the
      ancestors of Anthanassa and Phyciodes. Our study is the first to use a dated
      phylogeny to study the historical biogeography of a group of South American
      species of butterflies.

PMID- 17560802
TI  - Assessment of the canine model of rotator cuff injury and repair.
AB  - Animal shoulder models are used to systematically investigate the factors
      influencing rotator cuff injury and repair. Each model has advantages and
      disadvantages that must be considered in the context of the specific research
      questions being asked. This study evaluated the utility of the canine model for
      studies of acute, full-thickness rotator cuff tendon injury and repair. We found
      that time-zero failure load is dependent on the suture type and configuration
      used for repair. Acute, full-width tendon repairs fail anatomically within the
      first days after surgery in the canine model, regardless of suture type, suture
      configuration, or postoperative protocol. Robust scar tissue forms in the gap
      between the failed tendon end and the humerus, which can be visually,
      mechanically, and histologically misconstrued as tendon if an objective test of
      repair connectivity is not performed. We conclude that a full-width injury and
      repair model in the canine will provide a rigorous test of whether a new repair
      strategy or postoperative protocol, such as casting or temporary muscle
      paralysis, can maintain repair integrity in a high-load environment.
      Alternatively, a partial-width tendon injury model allows loads to be shared
      between the tendon repair and the remaining intact portion of the infraspinatus
      tendon and prohibits complete tendon retraction. Thus a partial-width injury in
      the canine may model the mechanical environment of many single tendon tears in
      the human injury condition and warrants further investigation.

PMID- 17560803
TI  - The effectiveness of digital infrared thermographic imaging in patients with
      shoulder impingement syndrome.
AB  - We prospectively evaluated 100 patients with unilateral impingement syndrome,
      before they underwent an arthroscopic subacromial decompression, to detect the
      relationship between clinical and operative findings and digital infrared
      thermographic imaging (DITI) findings in patients with shoulder impingement
      syndrome. The DITI system was used to measure the temperature of each patient's
      upper body, and the relative temperature values between involved and the
      uninvolved sides were used for analysis. A control group of 30 subjects without
      impingement syndrome was also evaluated. In DITI findings, 73% of patients had
      abnormal thermal changes in more than 1 of the 4 regions of interest: 51%
      displayed hypothermia, and 22% had hyperthermia. In the hypothermic group,
      limitation of shoulder motion was more prominent than in the hyperthermic and
      normal groups (P < .05). Other clinical findings did not correlate with the DITI
      findings, however. DITI can be used to reflect shoulder stiffness objectively in
      impingement syndrome, especially in those cases with a hypothermic thermal
      pattern.

PMID- 17560804
TI  - Commercially available extracellular matrix materials for rotator cuff repairs:
      state of the art and future trends.
AB  - Rotator cuff tears, a common source of shoulder pathology, are often the cause of
      debilitating shoulder pain, reduced shoulder function and compromised joint
      mechanics. The treatment, evaluation and management of this disease puts an
      annual financial burden of 3 billion US dollars on the US economy. Despite
      surgical advances, there is a high rate of recurrent tears ranging (20-70%) after
      surgical repair, particularly for chronic, large to massive cuff tears. The
      inability to obtain a high healing rate in these tears has fueled investigation
      in the use of extracellular matrix (ECM) derived materials as a scaffolds for
      rotator cuff tendon repair and regeneration. The present paper reviews the
      current state of knowledge regarding the mechanical and biological
      characteristics of commercially available ECM materials, delineates indications
      for their clinical use and suggests future directions in developing ECM scaffolds
      for rotator cuff repair.

PMID- 17560805
TI  - Relative contributions of infraspinatus and deltoid during external rotation in
      healthy shoulders.
AB  - Balanced forces around the shoulder are important for normal function; however,
      rehabilitation guidelines are not well defined because the muscle contributions
      and optimal exercise technique to recruit them are poorly understood. This study
      aimed to determine (1) the conditions of resisted isometric external rotation
      that optimized the contribution of infraspinatus and (2) the load of external
      rotation at which the adduction strategy was most effective at reducing deltoid
      contributions. Eighteen subjects with healthy shoulders (n = 36) performed
      resisted isometric external rotation at 3 increasing loads--10%, 40%, and 70% of
      their maximal resisted external rotation voluntary isometric contraction--with
      and without adduction. Surface electromyographic activity of the infraspinatus,
      posterior and middle deltoid, and pectoralis major was recorded and normalized
      against the average activity of all 4 muscles, representing each muscle's
      relative contribution to the task. To optimize the relative contribution of the
      infraspinatus with the least deltoid involvement during isometric external
      rotation, a load between 10% and 40% maximal voluntary isometric contraction is
      appropriate. At low loads, use of the adduction strategy during external rotation
      reduces middle deltoid involvement. In contrast, the posterior deltoid is
      activated in parallel with the infraspinatus at low loads and may even act as an
      adductor with the arm by the side. This study provides a useful guide to optimize
      rehabilitative exercises for rotator cuff dysfunction; in particular,
      highlighting that activation of the deltoid could be counterproductive to
      infraspinatus retraining.

PMID- 17560806
TI  - Bilateral reverse shoulder prosthesis in a patient with severe syringomyelia.

PMID- 17560807
TI  - Elastofibroma dorsi: diagnosis and treatment.
AB  - Elastofibroma dorsi is a rare, benign, soft tumor located at the inferior pole of
      the scapula. We report a series of 8 patients (5 women, 3 men), with a mean age
      of 67 years (range, 44-80 years), and discuss the clinical presentation,
      diagnosis, and treatment. Six lesions were unilateral, and 2 were bilateral. All
      patients were referred from other clinics with a large, unknown tumor of the
      back. Two patients presented with symptoms of pain and clunking of the scapula on
      shoulder abduction. Five underwent simple excision of the tumor. Preoperative
      diagnosis by magnetic resonance imaging showed agreement with the histopathologic
      diagnosis. Three patients had the postoperative complication of hematoma
      formation. Presumptive diagnosis is possible by careful clinical examination and
      magnetic resonance imaging. Because postoperative hematoma is unexpectedly
      frequent and symptomatic, radical resection should be avoided, and only
      excisional biopsy is necessary for histopathologic diagnosis.

PMID- 17560808
TI  - Treatment of malignant tumors of the proximal humerus with allograft-prosthesis
      composite reconstruction.
AB  - Malignant tumors of the proximal humerus are challenging to treat. Reconstruction
      with a metallic implant or allograft is the most common method, but each has
      known risks and frequent complications. Allograft-prosthesis composite
      reconstruction has not been widely used and may avoid problems posed by metal
      prostheses or allografts used alone. Six patients with malignant tumors of the
      proximal humerus were treated with allograft-prosthesis composite reconstruction
      after excision of the intra-articular tumor. Outcomes were assessed by use of the
      Disabilities of the Arm, Shoulder and Hand questionnaire; the Short Form 36 (SF
      36) Health Survey; and the American Shoulder and Elbow Surgeons Shoulder
      Assessment Form. Preoperative and postoperative scores at a mean of 55 months
      were compared. Disability increased after surgery based on the Disabilities of
      the Arm, Shoulder and Hand questionnaire and SF-36, although disability appeared
      to decrease with time. The mean mental component score on the SF-36 showed
      continued improvement with time after surgery. One asymptomatic nonunion was
      repaired, and painful loosening developed in one patient, requiring revision at
      45 months. Allograft-prosthesis composite reconstruction is a safe method for
      treating some malignant tumors of the proximal humerus, providing stable
      reconstruction and preserving function of the shoulder joint.

PMID- 17560809
TI  - Treatment of avascular necrosis of the capitulum of the humerus using a free
      vascularized osteoperiosteal graft from the medial condyle of the femur: a case
      report.

PMID- 17560810
TI  - Correlation of MRI and histopathology in epileptogenic parietal and occipital
      lobe lesions.
AB  - INTRODUCTION: To analyze the diagnostic accuracy of MRI in patients undergoing
      parietal and occipital lobe epilepsy surgery. METHODS: In a retrospective study,
      we analyzed MRI scans and neuropathology reports of 42 patients who had undergone
      resective epilepsy surgery in the parietal and occipital lobe between 1998 and
      2003. We evaluated, whether lesions were precisely characterized by MRI and
      whether lesion characterization allowed to estimate postsurgical seizure outcome.
      RESULTS: Within the categories epilepsy associated tumors, focal cortical
      dysplasias, vascular malformations, scarring, and others, MRI was concordant with
      histopathology in 36 of 42 (86%) lesions. Among the discordant lesions, one
      lesion was re-classified following MRI-histopathology synopsis, another two
      lesions represented new tumor entities (angiocentric neuroepithelial tumor,
      isomorphic astrocytoma) which have been described recently. Seizure freedom
      (Engel class I) one year following surgery was achieved in 25 patients (60%).
      Seizure outcome was different for lesion categories (Engel class I: epilepsy
      associated tumors, 62%; focal cortical dysplasias, 71%; vascular malformations,
      75%; scarring, 40%), and was unchanged if no lesion was found on preoperative
      MRI. CONCLUSION: If MRI and histopathology are discordant, not only the MRI
      findings may be debatable. MRI lesion detection is important, since chance of
      seizure freedom is low if no lesion is detected.

PMID- 17560811
TI  - Opioid receptor binding in parahippocampus of patients with temporal lobe
      epilepsy: its association with the antiepileptic effects of subacute electrical
      stimulation.
AB  - Opioid receptor binding was evaluated in parahippocampal cortex (PHC) obtained
      from patients with intractable mesial temporal lobe epilepsy (MTLE) with and
      without subacute high frequency electrical stimulation (HFS) in this brain area.
      Mu, delta and nociceptin receptor binding was determined by autoradiography in
      PHC of five patients (ESAE group) with MTLE history of 14.8 +/- 2.5 years and
      seizure frequency of 11 +/- 2.9 per month, two of them (40%) with mesial
      sclerosis. This group demonstrated antiepileptic effects following subacute HFS
      (130 Hz, 450 micros, 200-400 microA), applied continuously during 16-20 days in
      PHC. Values were compared with those obtained from patients with severe MTLE
      (history of 21.7 +/- 2.8 years and seizure frequency of 28.2 +/- 14 per month) in
      whom electrical stimulation did not induce antiepileptic effects (ESWAE group, n
      = 4), patients with MTLE in whom no electrical stimulation was applied (MTLE
      group, n = 4) and autopsy material acquired from subjects without epilepsy (n = 4
      obtained from three subjects). Enhanced 3H-DAMGO (MTLE, 755%; ESAE, 375%; ESWAE,
      693%), 3H-DPDPE (MTLE, 242%; ESAE, 80%; ESWAE, 346%) and 3H-nociceptin (MTLE,
      424%; ESAE, 217%; ESWAE, 451%) binding was detected in the PHC of all epileptic
      groups. However, tissue obtained from ESAE group demonstrated lower opioid
      receptor binding (3H-DAMGO, 44.5%, p < 0.05; 3H-DPDPE, 47%, p < 0.05; 3H
      nociceptin, 39.3%, p < 0.5) when compared with MTLE group. The present results
      indicate that a high effectiveness to the antiepileptic effects induced by HFS is
      associated with reduced opioid peptide binding.

PMID- 17560812
TI  - Further evidence for leptin involvement in cartilage homeostases.

PMID- 17560813
TI  - Two year longitudinal change and test-retest-precision of knee cartilage
      morphology in a pilot study for the osteoarthritis initiative.
AB  - OBJECTIVE: Fast low angle shot (FLASH) and double echo steady state (DESS)
      magnetic resonance imaging (MRI) acquisitions were recently cross-calibrated for
      quantification of cartilage morphology at 3T. In this pilot study for the
      osteoarthritis (OA) initiative we compare their test-retest-precision and
      sensitivity to longitudinal change. METHOD: Nine participants with mild to
      moderate clinical OA were imaged twice each at baseline, year 1 (Y1) and year 2
      (Y2). Coronal 1.5mm FLASH and sagittal 0.7mm DESS sequences were acquired; 1.5mm
      coronal multiplanar reformats (MPR) were obtained from the DESS. Patellar,
      femoral and tibial cartilage plates were quantified in a paired fashion, with
      blinding to time point. RESULTS: In the weight-bearing femorotibial joint,
      average precision errors across plates were 1.8% for FLASH, 2.6% for DESS, and
      3.0% for MPR-DESS. Volume loss at Y1 was not significant; at Y2 the average
      change across the femorotibial cartilage plates was -1.7% for FLASH, -2.8% for
      DESS, and -0.3% for MPR-DESS. Volume change in the lateral tibia (-5.5%; P<0.03),
      and in the medial (-2.9%; P<0.04) and lateral femorotibial compartments (-3.8%;
      P<0.03) were significant for DESS. CONCLUSIONS: FLASH, DESS and MPR-DESS all
      displayed adequate test-retest precision. Although the comparison between
      protocols is limited by the small number of participants and by the relatively
      small longitudinal change in cartilage morphology in this pilot study, the data
      suggest that significant change can be detected with MRI in a small sample of OA
      subjects over 2 years.

PMID- 17560814
TI  - Signal transduction mechanisms within the entorhinal cortex that support latent
      inhibition of cued fear conditioning.
AB  - Latent inhibition is a phenomenon by which pre-exposure to a conditioned-stimulus
      (CS), prior to subsequent pairings of that same CS with an unconditioned-stimulus
      (US), results in decreased conditioned responding to the CS. Previous work in our
      laboratory has suggested that the entorhinal cortex is critically involved in the
      establishment of latent inhibition of cued fear conditioning. Furthermore,
      utilizing systemic pharmacology, we have demonstrated a role for of NMDA
      receptors, protein kinase A (PKA), and mitogen activated protein kinase (MAPK,
      also known as ERK) in latent inhibition of cued fear conditioning, but until now,
      where these cell signaling cascades are critically activated during latent
      inhibition of cued fear was unknown. Here, we use direct drug infusion to
      demonstrate that cell signaling via NMDA receptors, the cAMP/PKA pathway, and the
      MAPK pathway within the entorhinal cortex are critically involved in latent
      inhibition of cued fear conditioning. In the present study, CS pre-exposed mice
      received 20 CS pre-exposures 24h prior to two pairings of the same CS with a 0.53
      mA foot shock US, while control animals receive no pre-exposure to the CS. The
      NMDA antagonist APV (0.25 or 2.5 microg/side), the cAMP inhibitor Rp-cAMP (1.8 or
      18.0 microg/side), or the MAPK inhibitor U0126 (0.1 or 1.0 microg/side) were
      directly infused into the entorhinal cortex prior to pre-exposure. All three
      drugs produced dose-dependent disruptions in latent inhibition of cued fear
      conditioning. Importantly, none of the drugs had any effect on cued fear
      conditioning when administered on training day, suggesting that the effects of
      each of the drugs were specific to CS pre-exposure. These results are discussed
      in relation to the potential mechanisms of plasticity that support latent
      inhibition of cued fear conditioning.

PMID- 17560815
TI  - Role of CA3 and CA1 subregions of the dorsal hippocampus on temporal processing
      of objects.
AB  - Previous research in the dorsal CA1 and dorsal CA3 subregions of the hippocampus
      has been shown to play an important role in mediating temporal order memory for
      spatial location information. What is not known is whether the dorsal CA3 and
      dorsal CA1 subregions of the hippocampus are also involved in temporal order for
      visual object information. Rats with dorsal CA1, dorsal CA3 or control lesions
      were tested in a temporal order task for visual objects using an exploratory
      paradigm. The results indicated that the controls and the dorsal CA3 lesioned
      rats preferred the first rather then the last object they had explored
      previously, indicating good memory for temporal order of object presentation. In
      contrast, rats with dorsal CA1 lesions displayed a profound deficit in
      remembering the order of the visual object presentations in that they preferred
      the last object rather than the first. All three groups of rats preferred a novel
      object compared to a previously explored object suggesting normal detection of
      visual object novelty. The results suggest that only the dorsal CA1, but not
      dorsal CA3, region is critical for processing temporal information for visual
      objects without affecting the detection of new visual objects.

PMID- 17560816
TI  - Molecular genetics of pituitary development in zebrafish.
AB  - The pituitary gland of vertebrates consists of two major parts, the
      neurohypophysis (NH) and the adenohypophysis (AH). As a central part of the
      hypothalamo-hypophyseal system (HHS), it constitutes a functional link between
      the nervous and the endocrine system to regulate basic body functions, such as
      growth, metabolism and reproduction. The development of the AH has been
      intensively studied in mouse, serving as a model for organogenesis and
      differential cell specification. However, given that the AH is a relatively
      recent evolutionary advance of the chordate phylum, it is also interesting to
      understand its development in lower chordate systems. In recent years, the
      zebrafish has emerged as a powerful lower vertebrate system for developmental
      studies, being amenable for large-scale genetic approaches, embryological
      manipulations, and in vivo imaging. Here, we present an overview of current
      knowledge of the mechanisms and genetic control of pituitary formation during
      zebrafish development. First, we describe the components of the zebrafish HHS,
      and the different pituitary cell types and hormones, followed by a description of
      the different steps of normal pituitary development. The central part of the
      review deals with the genes found to be essential for zebrafish AH development,
      accompanied by a description of the corresponding mutant phenotypes. Finally, we
      discuss future directions, with particular focus on evolutionary aspects, and
      some novel functional aspects with growing medical and social relevance.

PMID- 17560817
TI  - Use of a nonhomologous end joining deficient strain (Deltaku70) of the ergot
      fungus Claviceps purpurea for identification of a nonribosomal peptide synthetase
      gene involved in ergotamine biosynthesis.
AB  - The ergot fungus Claviceps purpurea uses mainly the nonhomologous-end-joining
      (NHEJ) system for integration of exogenous DNA, leading to a low frequency of
      homologous integration (1-2%). To improve gene targeting efficiency we deleted
      the C. purpurea ku70 gene in two different strains: the pathogenic strain 20.1
      and the apathogenic, ergot alkaloid producing strain P1. The mutants were not
      impaired in vegetative and pathogenic development nor alkaloid production. Gene
      targeting efficiency was significantly increased (50-60%) in the Deltaku70
      mutants. The P1 Deltaku70 strain (producing ergotamine and ergocryptine) was used
      for targeted deletion of lpsA1, one of the two trimodular NRPS genes present in
      the alkaloid gene cluster, encoding D-lysergyl peptide synthetases involved in
      formation of the tripeptide moiety of ergopeptines. Mutants lacking the lpsA1
      gene were shown to be incapable of producing ergotamine but were still able to
      produce ergocryptine, proving that LpsA1 is involved in ergotamine biosynthesis.

PMID- 17560818
TI  - Similarity of European porcine reproductive and respiratory syndrome virus
      strains to vaccine strain is not necessarily predictive of the degree of
      protective immunity conferred.
AB  - The objective of this study was to determine the degree of protection conferred
      by a Lelystad-like modified live virus (MLV) vaccine against a heterologous wild
      type porcine reproductive and respiratory syndrome virus (PRRSV) isolate of the
      same cluster. For this purpose, fourteen 3-week-old piglets were divided into
      three groups: Group A pigs were vaccinated with a modified live virus vaccine,
      Group B pigs were used as positive controls, and Group C pigs as negative
      controls. Twenty-eight days after the last dose of vaccine, all pigs in Groups A
      and B were inoculated with the Spanish PRRSV strain 5710. To evaluate efficacy,
      clinical signs were recorded and the presence of challenge virus was determined
      by virus isolation in blood samples and nasal swabs collected at various time
      points post-challenge (p.c.) and in tissue samples collected at necropsy 24 days
      p.c. After challenge, moderate clinical signs were observed in pigs from Groups A
      and B. In addition, all vaccinated pigs were viremic at least once, although
      viremia tended to be more sporadic in this group than in Group B pigs. PRRSV was
      detected in at least one tissue sample from four out of five pigs from Group A
      and in all pigs from Group B. The results indicate that the protection conferred
      by the MLV vaccine used in this study against a closely related virulent strain
      was only partial. The findings suggest that the degree of genetic homology of
      ORF5 between MLV vaccine and challenge isolate is not a good predictor of vaccine
      efficacy.

PMID- 17560819
TI  - Home visits by specially trained nurses after discharge from multi-disciplinary
      pain care: a cost consequence analysis based on a randomised controlled trial.
AB  - OBJECTIVES: To analyse the cost consequences of a nurse follow-up intervention
      for chronic non-malignant pain patients discharged from multidisciplinary pain
      treatment. METHODS: The cost consequence analysis was based on a prospective,
      randomised controlled trial where 102 consecutive patients were randomised to
      either an intervention group (n=52) or a control group (n=50). During the 2-year
      intervention period, nurses visited patients every 4th month (7 times in total).
      Changes in health status were measured by the 8 SF-36 sub-scales. Intervention
      costs were based on prospective registrations of nurses' time use. Data on health
      care cost and resource use were collected retrospectively from administrative
      registers. RESULTS: No statistically significant differences in health status
      were observed between the two groups after the 2-year intervention period. The
      cost of the nurse intervention programme itself was 35,000 euro (2004-prices).
      The average cost per patient was estimated at 668 euro per patient. During the
      observation period the average patient in the intervention group used other
      health care resources worth 4004 euro, while the average patient in the control
      group used 7464 euro. This difference (3460 euro, 46%) was not statistically
      significant. CONCLUSION: The nurse intervention did not significantly influence
      patients' health status. Patients in the intervention group tended to use fewer
      health care resources than those in the control group and the cost of the
      intervention was more than balanced out by savings in other health care
      resources.

PMID- 17560820
TI  - Neurological and brain MRS findings in patients with Gaucher disease type 1.
AB  - Gaucher disease type 1 (GD1) is an autosomal recessive lysosomal storage
      disorder, characterised by accumulation of glycosphingolipids in visceral organs.
      Although considered non-neuronopathic neurological involvement has been reported
      in single cases. The aim of our study was to investigate central and peripheral
      nervous system involvement in patients with GD1. We investigated nine unrelated
      patients with GD1 by three-dimensional cerebral 1H-magnetic resonance
      spectroscopic imaging and clinical and neurophysiological tests. We found an
      increased choline level on MRS in four patients. One of these patients had mixed
      axonal neuropathy and subclinical involvement of the central somatosensory tract
      as well as monoclonal gammopathy. One patient with normal cerebral choline levels
      had evidence of bilateral carpal tunnel syndrome upon neurophysiological exam.
      The N370S mutation was found in 11 out of 18 alleles. Three patients were
      compound heterozygous for the L444P mutation. There was no correlation between
      increased cerebral choline levels and type of mutations. MRS findings suggest
      that in patients with classical non-neuronopathic GD1, the brain is involved at a
      subclinical level in some patients.

PMID- 17560821
TI  - Structure-based epitope and PEGylation sites mapping of phenylalanine ammonia
      lyase for enzyme substitution treatment of phenylketonuria.
AB  - Protein and peptide therapeutics are of growing importance as medical treatments
      but can frequently induce an immune response. This work describes the combination
      of complementary approaches to map the potential immunogenic regions of the yeast
      Rhodosporidium toruloides phenylalanine ammonia-lyase (PAL, EC 4.3.1.5) and to
      engineer the protein as a human therapeutic agent for the treatment of
      phenylketonuria (PKU), an inherited metabolic disorder. The identification of B
      and T cell epitopes on the PAL protein was performed by computational predictions
      based on the antigenicity and hydrophilicity of proteins, as well as by
      experimental epitope mapping using a PepSpots peptide array (Jerini AG). Human T
      cell epitope mapping was performed by applying the computational EpiMatrix
      algorithm (EpiVax, Inc.) for MHC Class I and Class II associated T cell epitopes
      on PAL, which predicts which sequences are associated with binding to several
      different HLA alleles, a requirement for antigen presentation and subsequent
      primary immune response. By chemical modification through PEGylation of surface
      lysine residues, it is possible to cover the immunogenic regions of a protein. To
      evaluate this strategy, we used mass spectrometry to determine which of the
      immunogenic epitopes are covered by the covalent PEGylation modification
      strategy. This approach has allowed us to determine whether additional lysines
      are needed in specific residue locations, or whether certain lysine residues can
      be removed in order to accomplish complete molecular coverage of the therapeutic
      enzyme.

PMID- 17560822
TI  - Alpha-aminoadipic semialdehyde is the biomarker for pyridoxine dependent epilepsy
      caused by alpha-aminoadipic semialdehyde dehydrogenase deficiency.

PMID- 17560823
TI  - Acute non-ambulatory tetraparesis attributable to cranial cervical intervertebral
      disc disease in a cat.
AB  - A 10-year-old domestic longhair cat was presented for acute non-ambulatory
      tetraparesis. Clinicopathologic diagnostics revealed no abnormalities. Cervical
      myelogram revealed an extradural compressive lesion consistent with
      intervertebral disc disease of the C2-C3 intervertebral disc space. Ventral slot
      decompression confirmed the presence of extruded intervertebral disc material
      into the vertebral canal of the C2-C3 intervertebral space. The patient succumbed
      to cardiorespiratory arrest 3 days postoperatively.

PMID- 17560824
TI  - Escherichia vulneris as a cause of bacteremia in a patient with chronic
      lymphocytic leukemia.

PMID- 17560825
TI  - Assessment of fall-risk by means of a neural network based on parameters assessed
      by a wearable device during posturography.
AB  - We have investigated the use of an Artificial Neural Network (ANN) for the
      assessment of fall-risk (FR) in patients with different neural pathologies. The
      assessment integrates a clinical tool based on a wearable device (WD) with
      accelerometers (ACCs) and rate gyroscopes (GYROs) properly suited to identify
      trunk kinematic parameters that can be measured during a posturography test with
      different constraints. Our ANN--a Multi Layer Perceptron Neural Network with four
      layers and 272 neurones--shows to be able to classify patients in three well
      known fall-risk levels. The training of the neural network was carried on three
      groups of 30 subjects with different Fall-Risk Tinetti scores. The validation of
      our neural network was carried out on three groups of 100 subjects with different
      Fall-Risk Tinetti scores and this validation demonstrated that the neural network
      had high specificity (> or =0.88); sensitivity (> or =0.87); area under Receiver
      Operator Characteristic Curves (>0.854).

PMID- 17560827
TI  - Probucol therapy overcomes the reproductive defect in CTP: phosphocholine
      cytidylyltransferase beta2 knockout mice.
AB  - The synthesis of phosphatidylcholine (PtdCho), the major phospholipid in
      mammalian cells, is regulated by the CTP:phosphocholine cytidylyltransferase
      (CCT). Loss of the CCTbeta2 isoform expression in mice results in gonadal
      dysfunction. CCTbeta2(-/-) females exhibit ovarian tissue disorganization with
      progressive loss of follicle formation and oocyte maturation. Ultrastructure
      revealed a disrupted association between ova and granulosa cells and disorganized
      Golgi apparati in oocytes of CCTbeta2(-/-) mice. Probucol is a cholesterol
      lowering agent that stimulates the uptake and retention of lipids carried by
      lipoproteins in peripheral tissues. Probucol therapy significantly lowered both
      serum cholesterol and PtdCho levels. Probucol therapy increased fertility in the
      CCTbeta2(-/-) females 100%, although it did not completely correct the phenotype,
      the morphological abnormalities in the knockout ovaries or itself stimulate CCT
      activity directly. These data indicated that a deficiency in de novo PtdCho
      synthesis could be complemented by altering the metabolism of serum lipoproteins,
      an alternative source for cellular phospholipid.

PMID- 17560826
TI  - Modulation of PPAR activity via phosphorylation.
AB  - Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear
      receptor superfamily of transcription factors that respond to specific ligands by
      altering gene expression in a cell-, developmental- and sex-specific manner.
      Three subtypes of this receptor have been discovered (PPARalpha, beta and gamma),
      each apparently evolving to fulfill different biological niches. PPARs control a
      variety of target genes involved in lipid homeostasis, diabetes and cancer.
      Similar to other nuclear receptors, the PPARs are phosphoproteins and their
      transcriptional activity is affected by cross-talk with kinases and phosphatases.
      Phosphorylation by the mitogen-activated protein kinases (ERK- and p38-MAPK),
      Protein Kinase A and C (PKA, PKC), AMP Kinase (AMPK) and glycogen synthase kinase
      3 (GSK3) affect their activity in a ligand-dependent or -independent manner. The
      effects of phosphorylation depend on the cellular context, receptor subtype and
      residue metabolized which can be manifested at several steps in the PPAR
      activation sequence including ligand affinity, DNA binding, coactivator
      recruitment and proteasomal degradation. The review will summarize the known PPAR
      kinases that directly act on these receptors, the sites affected and the result
      of this modification on receptor activity.

PMID- 17560828
TI  - Species of the parasitic genus Duboscquella are members of the enigmatic Marine
      Alveolate Group I.
AB  - Small subunit ribosomal RNA gene sequences of Duboscquella spp. infecting the
      tintinnid ciliate, Favella ehrenbergii, were determined. Two parasites were
      sampled from different localities. They are morphologically similar to each other
      and both resemble D. aspida. Nevertheless, two distinct sequences (7.6%
      divergence) were obtained from them. Phylogenetic trees inferred from maximum
      likelihood and maximum parsimony revealed that these two Duboscquella spp.
      sequences are enclosed in an environmental clade named Marine Alveolate Group I.
      This clade consists of a large number of picoplanktonic organisms known only from
      environmental samples from various parts of the ocean worldwide, and which
      therefore lack clear characterization and identification. Here, we provide
      morphological and genetic characterization of these two Duboscquella genotypes
      included in this enigmatic clade. Duboscquella spp. produce a large number of
      small flagellated spores as dispersal agents and the presence of such small cells
      partially explains why the organisms related to these parasites have been
      detected within environmental genetic libraries, built from picoplanktonic size
      fractions of environmental samples. The huge diversity of the Marine Alveolate
      Group I and the finding that parasites from different marine protists belong to
      this lineage suggest that parasitism is a widespread and ecologically relevant
      phenomenon in the marine environment.

PMID- 17560829
TI  - Poor peak dorsiflexor torque associated with incidence of ankle injury in elite
      field female hockey players.
AB  - This study set out to determine the incidence of ankle injuries amongst
      provincial female field hockey players in KwaZulu-Natal (KZN), South Africa,
      during the 2004 field hockey season and relate this to their injury and playing
      profile, proprioceptive ability and peak isokinetic torque of the ankle plantar
      and dorsiflexor muscles. Players participating in the senior, U21 and U19/high
      school provincial A teams (n=47) detailed their hockey playing and training
      history and injuries sustained during the 2004 season. A subsample of injured and
      matched, uninjured controls (n=18) underwent anthropometric, proprioceptive and
      isokinetic testing. Incidence of injury in the 2004 season was 0.98 per player or
      6.32 injuries per 1000 player/h(-1), with 25.5% of players (n=12) reporting
      injuries to the ankle joint. All ankle injuries occurred on artificial turf and
      75% occurred during a match. Forwards and links that had been playing for six to
      seven years presented with the highest incidence of ankle injuries. Injured
      players were able to maintain balance on a proprioceptive board for 10.31+/-8.2 s
      versus 23.9+/-15.3 s in matched, uninjured controls (p=0.078). Both mean (27.4+/
      5.5 Nm versus 32.7+/-4.7 Nm) and median (27.0, 23.0-31.5 versus 31.8, 30.0-35.1
      Nm) peak isokinetic torque of the dorsiflexors of injured legs was significantly
      lower than in uninjured, contralateral legs of the injured players (p=0.01 and
      0.03, respectively). Poor peak dorsiflexion torque in the injured leg was
      identified as a factor associated with ankle injury in this sample of injured,
      elite field hockey players.

PMID- 17560830
TI  - Isokinetic neck strength profile of senior elite rugby union players.
AB  - To delineate and compare the isokinetic neck strength profile of senior elite
      rugby players. One hundred and eighty-nine rugby players (mean; 95% confidence
      intervals: 24.31; 23.87-24.75 years) were sampled from South African provincial
      teams and assessed anthropometrically and isokinetically according to a set
      protocol. Specially designed equipment was used to perform the isokinetic
      assessment and gathered data were analysed according to positional categories
      (front, second, back row and backline players). Second row forwards performed the
      best in the measure of peak flexion (44.04; 40.41-47.67Nm) and lateral flexion
      right (69.42; 63.36-75.48Nm) and left (66.31; 61.21-71.41Nm) torque, while the
      front row forwards performed best in peak extension torque (65.60; 62.12
      69.08Nm). Few significant differences (p<0.05) existed between the forward
      positional categories. However, they all proved to be significantly (p<0.05)
      stronger and more powerful than the backline players. Peak torque values relative
      to body weight indicated much less variability between all positional categories.
      Cervical flexor to extensor ratios showed that front row forwards (65; 61.94
      68.06%) had significantly (p<0.05) lower ratios than the other positional
      categories. Absolute peak torque is an important positional prerequisite,
      especially among the front row forwards. Isokinetic neck strength data presented
      here provides a benchmark for the effective and quantified comparison of neck
      strength variables, assisting with preparticipation screening and the effective
      rehabilitation of injured senior rugby union players.

PMID- 17560831
TI  - Angiogenesis markers (VEGF, soluble receptor of VEGF and angiopoietin-1) in very
      early arthritis and their association with inflammation and joint destruction.
AB  - OBJECTIVE: To investigate the involvement of angiogenesis markers in very early
      arthritis patients and their relevance to predict further joint destruction.
      METHODS: Levels of Vascular Endothelial Growth Factor (VEGF), angiopoietin-1 (Ang
      1), and soluble Fms-like tyrosine kinase-1 (sFlt-1) were measured by ELISA in
      serum samples from 310 patients having polyarthritis, evolving for less than 6
      months (VErA cohort). Each angiogenesis marker was measured at baseline and one
      year later. X-rays of hands and feet were carried out at inclusion and after 1
      year and read using the van der Heidje-modified Sharp method. RESULTS: At
      baseline and after 1 year, VEGF levels were correlated with clinical and
      biological parameters of inflammation. We also observed a positive correlation
      between sFlt-1 levels and biological inflammation (Erythrocyte Sedimentation Rate
      (ESR): r=0.17, p=0.006; C Reactive Protein: r=0.14, p=0.02). Angiopoietin-1
      levels were correlated with ESR (r=0.12, p=0.04). Interestingly, only VEGF levels
      measured at baseline were correlated with Disease Activity Score measured 1 year
      later. Relationship between angiogenesis markers and radiographic progression was
      also evaluated. VEGF and Ang-1 levels measured at inclusion were related with
      Sharp score after one year (VEGF: r=0.21, p<0.001; Ang-1: r=0.24, p<0.001;
      Spearman's test). Moreover, VEGF levels were higher in patients with radiographic
      progression (p=0.002). CONCLUSION: Serum concentrations of VEGF, sFlt-1 and
      angiopoietin-1 were correlated to parameters of inflammation and to bone
      destruction in early arthritis. These results contribute to demonstrate that
      angiogenesis reflects disease severity and angiogenesis markers might become a
      new useful tool to evaluate disease activity and to estimate outcome for patients
      with inflammatory arthritis.

PMID- 17560832
TI  - Immunophenotypic patterns of CD8+ T cell subsets expressing CD8alphaalpha and IL
      7Ralpha in viremic, aviremic and slow progressor HIV-1-infected subjects.
AB  - Evidence from animal models suggests that the expression of CD8alphaalpha
      homodimer on CD8(+) T cells plays a key role in the generation of long-lived
      memory cells. Here, we studied the quantitative alterations of CD8(+) T cell
      subsets expressing CD8alphaalpha, interleukin-7 receptor (IL-7Ralpha) and
      activation markers in HIV-1-infected individuals including aviremic, viremic and
      slow progressor subjects using eight-color flow cytometry. Compared to slow
      progressor subjects, expression of CD8alphaalpha was significantly reduced in
      aviremic and viremic patients and this reduction occurred mainly within central
      memory cell subsets and not in naive and effector memory compartments.
      Persistence of antigenemia leads to IL-7Ralpha loss mainly on central and pre
      terminal memory CD8(+) T cell subsets in viremic patients but not in slow
      progressor subjects. Compared to aviremic and viremic patients, slow progressor
      subjects had lower levels of IL-7 and reduced activated cells. The expression of
      CD8alphaalpha was not significantly related to IL-7Ralpha although negative
      associations were evidenced within all CD8(+) T cell subsets. Collectively, these
      results further advance the characterization of immunophenotypic patterns of
      CD8(+) T cell subsets expressing CD8alphaalpha/IL-7Ralpha and provide new
      insights into the ability of HIV-1 infection to alter memory cell population.

PMID- 17560833
TI  - Galectin-9 protects mice from the Shwartzman reaction by attracting prostaglandin
      E2-producing polymorphonuclear leukocytes.
AB  - Galectins play a crucial role in the modulation of innate and adaptive immunity.
      Here we show that galectin-9 (Gal-9) exhibits an anti-inflammatory role in LPS
      induced inflammation. Intraperitoneal LPS injection enhances Gal-9 levels as well
      as promotes the production of pro-inflammatory cytokines, e.g., TNF-alpha, IFN
      gamma and IL-12. We found that Gal-9 administration results in the protection of
      mice from the Shwartzman reaction, and Gal-9-deficient mice became susceptible to
      the Shwartzman reaction, thus implying the anti-inflammatory activity of Gal-9
      against LPS-induced inflammation. Indeed, Gal-9 treatment together with LPS
      suppresses production of these pro-inflammatory cytokines, while it rather
      enhances than suppresses IL-4 and IL-10 production. We also found that LPS
      induced elevation of TNF-alpha, IFN-gamma, and IL-12 does not occur in Gal-9
      transgenic mice. Moreover, Gal-9 induces Gr-1(+) cell; probably polymorphonuclear
      leukocyte (PMN), as well as infiltration in to the peritoneal cavity, causing us
      to hypothesize PMNs are involved in Gal-9-mediated suppression. The fact that Gal
      9 does not suppress LPS-induced TNF-alpha, IFN-gamma and IL-12 production in
      neutropenic mice, and that it does not protect those mice from the Shwartzman
      reaction, confirms the involvement of PMN in regulation. PMN attracted by Gal-9
      produce PGE(2), which LPS-induced TNF-alpha production from the peritoneal
      macrophages is suppressed, while PMNs attracted by casein produce less PGE(2) and
      fail to suppress LPS-induced TNF-alpha production. Our data suggest that Gal-9
      regulates LPS-induced inflammation and protects mice from the Shwartzman reaction
      by attracting PGE(2)-producing PMN.

PMID- 17560834
TI  - Diagnosis of abnormal uterine bleeding.
AB  - Abnormal uterine bleeding is an extremely common indication for referral to a
      gynaecologist. This chapter examines the modes of presentation and the causes of
      such symptoms, which range from physiological variations to more sinister
      underlying pathology. A thorough understanding of these causes is required to
      direct investigation in an appropriate manner. The full range of possible
      investigations is discussed with emphasis on how to choose the most appropriate
      tests for a particular patient. This is fundamental to ensure that tests are
      pertinent and streamlined, and to prevent unnecessary anxiety and delay. Once the
      underlying causes have been clarified, a suitable management plan can be made.

PMID- 17560835
TI  - The use of biomarkers in biomonitoring: a 2-tier approach assessing the level of
      pollutant-induced stress syndrome in sentinel organisms.
AB  - The paper outlines a 2-tier approach for wide-scale biomonitoring programmes. To
      obtain a high level of standardization, we suggest the use of caged organisms
      (mussels or fish). An "early warning", highly sensitive, low-cost biomarker is
      employed in tier 1 (i.e. lysosomal membrane stability (LMS) and survival rate, a
      marker for highly polluted sites). Tier 2 is used only for animals sampled at
      sites in which LMS changes are evident and there is no mortality, with a complete
      battery of biomarkers assessing the levels of pollutant-induced stress syndrome.
      Possible approaches for integrating biomarker data in a synthetic index are
      discussed, along with our proposal to use a recently developed Expert System. The
      latter system allows a correct selection of biomarkers at different levels of
      biological organisation (molecular/cellular/tissue/organism) taking into account
      trends in pollutant-induced biomarker changes (increasing, decreasing, bell
      shape). A selection of biomarkers of stress, genotoxicity and exposure usually
      employed in biomonitoring programmes is presented, together with a brief overview
      of new biomolecular approaches.

PMID- 17560836
TI  - From population structure to genetically-engineered vectors: new ways to control
      vector-borne diseases?
AB  - Epidemiological studies on vectors and the pathogens they can carry (such as
      Borrelia burgdorferi) are showing some correlations between infection rates and
      biodiversity highlighting the "dilution" effects on potential vectors. Meanwhile
      other studies comparing sympatric small rodent species demonstrated that rodent
      species transmitting more pathogens are parasitized by more ectoparasite species.
      Studies on population structure and size have also proven a difference on the
      intensity of the parasitic infection. Furthermore, preliminary results in genetic
      improvement in mosquitoes (genetic markers, sexing, and genetic sterilization)
      will also increase performance as it has already been shown in field applications
      in developing countries. Recent results have greatly improved the fitness of
      genetically-modified insects compared to wild type populations with new
      approaches such as the post-integration elimination of transposon sequences,
      stabilising any insertion in genetically-modified insects. Encouraging results
      using the Sterile Insect Technique highlighted some metabolism manipulation to
      avoid the viability of offspring from released parent insect in the wild. Recent
      studies on vector symbionts would also bring a new angle in vector control
      capabilities, while complete DNA sequencing of some arthropods could point out
      ways to block the deadly impact on animal and human populations. These new
      potential approaches will improve the levels of control or even in some cases
      would eradicate vector species and consequently the vector-borne diseases they
      can transmit. In this paper we review some of the population biology theories,
      biological control methods, and the genetic techniques that have been published
      in the last years that are recommended to control for vector-borne diseases.

PMID- 17560837
TI  - Recovery of cell cycle delay following targeted gene repair by oligonucleotides.
AB  - We have previously shown that activation of the homologous recombinational repair
      pathway leads to a block of cell division in corrected cells, possibly through
      the activity of checkpoint proteins Chk1 and Chk2. In this study, we examine the
      long-term impact of this stalling on the growth of cells that have enabled gene
      repair events. Using a mutated eGFP gene as an episomal reporter, we show that
      corrected (eGFP-positive) cells contain only a few active replication templates 2
      weeks after electroporation, yet do not display an apoptotic or senescent
      phenotype. By 6 weeks after electroporation, cells resume active replication with
      a cell cycle profile that is comparable to that of the non-corrected (eGFP
      negative) population. These results indicate that the initial stalling is
      transient and eGFP-positive cells eventually resume a normal phenotypic growth
      pattern, allowing for passaging and expansion in vitro.

PMID- 17560838
TI  - Serum albumins have five sites for binding of cationic dendrimers.
AB  - The detailed analysis of the interaction between PAMAM G4 dendrimer and serum
      albumins was performed using circular dichroism, isothermal titration
      calorimetry, capillary electrophoresis, zeta-potential and fluorescence
      polarization. It was shown that serum albumins and PAMAM G4 dendrimer form the
      complex with stoichiometry of 4-6:1 for G4:HSA and 4-5:1 for G4:BSA molar ratio.
      The possible sites of PAMAM G4 dendrimers binding to protein surface were
      discussed. Also, it has been proposed that dendrimer does not significantly
      affect the protein secondary structure studied by circular dichroism.

PMID- 17560839
TI  - Physical activity and femoral neck bone strength during childhood: the Iowa Bone
      Development Study.
AB  - Structural adaptations of bone to changing mechanical loads have recently been
      documented during adolescence. However, little is known about how bone adapts
      structurally during the earlier years. Using a longitudinal observational design
      spanning 6 years of growth (age range 4 to 12 years), we investigated
      associations between everyday physical activity and hip geometry in a cohort of
      healthy Midwestern children (n=468). Femoral neck (FN) cross sectional area (CSA,
      cm(2)) and FN section modulus (Z, cm(3)) were used to describe hip geometry. CSA
      and Z, indices of axial and bending strength, were assessed using dual-energy X
      ray absorptiometry (DXA) scans and the hip structure analysis (HSA) program.
      Moderate and vigorous physical activity (MVPA) was assessed using accelerometry
      based activity monitors and calculated as the number of minutes > or =3000
      accelerometry movement counts. Data were analyzed using multilevel (random- and
      fixed-effects) regression models with adjustment for age (year), height (cm), and
      weight (kg) or lean mass (kg). For boys and girls, MVPA was a positive
      independent predictor of CSA and Z (p<0.05). On average, children who
      participated in 40 min of MVPA per day would be expected to have 3% to 5% greater
      CSA and Z than peers participating in 10 min of MVPA per day. Ten-minute
      increases in daily MVPA had similar effects on CSA in girls and Z in boys as did
      each additional 1 kg of body weight. When lean mass was substituted for weight,
      MVPA continued to be a positive independent predictor of CSA and Z for boys, but
      not girls. This study demonstrates that everyday amounts of physical activity in
      children are associated with indices of FN bone strength during childhood.
      Differences in lean mass mediate associations between physical activity and hip
      geometry in girls, but only somewhat in boys. These results suggest that physical
      activity is an important contributor to bone strength prior to adolescence and
      that increasing levels of physical activity during childhood are likely to
      enhance optimal bone strength.

PMID- 17560840
TI  - ADAMTS-1 increases the three-dimensional growth of osteoblasts through type I
      collagen processing.
AB  - The multi-domain neutral endopeptidase, ADAMTS-1 (a disintegrin and
      metalloprotease with thrombospondin repeats) is induced by parathyroid hormone
      (PTH) in rat osteoblasts and has therefore been suggested to be involved in
      initiation of bone remodeling. However, its function(s) in bone cells have not
      been studied. Here, we first establish that ADAMTS-1 protein is rapidly and
      transiently produced by human primary osteoblasts in response to PTH (1-34). We
      also show that ADAMTS-1 is specifically in close proximity to collagen fibrils in
      bone tissue using ultrastructural immunolabeling. To study the consequence(s) of
      ADAMTS-1 metalloprotease production in osteoblastic cells, human osteosarcoma
      cells (SaOS-2), were forced to express either wild-type (wtATS) or a point
      mutated (pmATS) metalloprotease dead ADAMTS-1. SaOS-2 cells expressing wtATS had
      a growth advantage and increased collagenolytic activity when seeded inside a
      collagen type I gel but exhibited a reduced migration in a scratch wound assay.
      Immunolabeling of moving cells shows ADAMTS-1 to be located towards the direction
      of cellular migration. Finally, Western analysis demonstrated excess accumulation
      of mature collagen type I alpha1 species in the extracellular matrix together
      with increased release of distinct small collagen fragments into the conditioned
      media, by cultures of wtATS cells compared to pmATS cells. These results show
      that ADAMTS-1 has both the opportunity in bone and capability in vitro to induce
      collagen type I processing, together with a positive influence on osteoblastic
      three-dimensional growth. Although it is not clear at present if ADAMTS-1
      promotes collagen degradation directly or indirectly, it shows that ADAMTS-1
      activity can have a profound influence on the osteoblast phenotype, inhibiting
      migration on a planar substrate but enhancing growth in a collagen scaffold.
      These findings further establish ADAMTS-1 as a potentially important protein in
      PTH induced bone remodeling.

PMID- 17560841
TI  - Dehydroepiandrosterone affects Trypanosoma cruzi tissue parasite burdens in rats.
AB  - Dehydroepiandrosterone (DHEA), the predominant steroid hormone produced by
      adrenal glands has significant effects on the immune system. DHEA enhances immune
      responses against a wide range of viral, bacterial, and parasitic pathogens. In
      the present study, we investigated the effects of DHEA treatment during the acute
      phase of experimental Trypanosoma cruzi infection. Male and female Wistar rats
      were infected with the Y strain of T. cruzi and treated subcutaneously with 40
      mg/kg body weight/day of DHEA. Myocardial parasitism and inflammation were always
      present in the heart during the acute phase, in male and female infected animals,
      regardless of DHEA treatment, but the numbers of amastigote nests in
      cardiomyocytes were significantly lower in DHEA-treated rats. At the end of the
      acute phase, the nests became rare or virtually absent in all experimental
      infections. Histological analysis of the adrenal glands showed that treated males
      displayed an absence of parasites. DHEA treatment also resulted in reduced
      parasitisim of heart and adrenal glands, as indicated by fewer and smaller
      amastigote burdens, and less inflammatory infiltrate and tissue disorganization.
      DHEA treatment also resulted in thymic atrophy as measured both by reduced weight
      and by a reduction in the number of cultured activated thymocytes. In vitro
      analysis showed the number of activated macrophages was higher in treated
      animals. Antibody levels were monitored by complement-mediated lysis. Higher
      titers were observed in females when compared to males; but DHEA treatment
      enhanced the percentage of lysis for both sexes. These findings suggest that DHEA
      can play a role in the control of parasite multiplication.

PMID- 17560842
TI  - Review of non-reactive and reactive wetting of liquids on surfaces.
AB  - Wettability is a tendency for a liquid to spread on a solid substrate and is
      generally measured in terms of the angle (contact angle) between the tangent
      drawn at the triple point between the three phases (solid, liquid and vapour) and
      the substrate surface. A liquid spreading on a substrate with no
      reaction/absorption of the liquid by substrate material is known as non-reactive
      or inert wetting whereas the wetting process influenced by reaction between the
      spreading liquid and substrate material is known as reactive wetting. Young's
      equation gives the equilibrium contact angle in terms of interfacial tensions
      existing at the three-phase interface. The derivation of Young's equation is made
      under the assumptions of spreading of non-reactive liquid on an ideal (physically
      and chemically inert, smooth, homogeneous and rigid) solid, a condition that is
      rarely met in practical situations. Nevertheless Young's equation is the most
      fundamental starting point for understanding of the complex field of wetting.
      Reliable and reproducible measurements of contact angle from the experiments are
      important in order to analyze the wetting behaviour. Various methods have been
      developed over the years to evaluate wettability of a solid by a liquid. Among
      these, sessile drop and wetting balance techniques are versatile, popular and
      provide reliable data. Wetting is affected by large number of factors including
      liquid properties, substrate properties and system conditions. The effect of
      these factors on wettability is discussed. Thermodynamic treatment of wetting in
      inert systems is simple and based on free energy minimization where as that in
      reactive systems is quite complex. Surface energetics has to be considered while
      determining the driving force for spreading. Similar is the case of spreading
      kinetics. Inert systems follow definite flow pattern and in most cases a single
      function is sufficient to describe the whole kinetics. Theoretical models
      successfully describe the spreading in inert systems. However, it is difficult to
      determine the exact mechanism that controls the kinetics since reactive wetting
      is affected by a number of factors like interfacial reactions, diffusion of
      constituents, dissolution of the substrate, etc. The quantification of the effect
      of these interrelated factors on wettability would be useful to build a
      predictive model of wetting kinetics for reactive systems.

PMID- 17560843
TI  - Depression and mood indicators in newly diagnosed glaucoma patients.
AB  - PURPOSE: To assess depression and mood indicators in subjects newly diagnosed
      with chronic open-angle glaucoma. DESIGN: Cross-sectional study of data from a
      randomized clinical trial. METHODS: Newly-diagnosed glaucoma patients enrolled in
      the Collaborative Initial Glaucoma Treatment Study (CIGTS) responded at baseline
      to quality-of-life (QOL) telephone interviews. We studied responses to the 33
      item Visual Activities Questionnaire (VAQ), six items from a disease-specific
      Health Perceptions Index (HPI), and eight questions from the Center for
      Epidemiological Studies Depression Scale (CES-D). We correlated the responses to
      the HPI and the CES-D with visual acuity (VA) and CIGTS visual field (VF) as well
      as to the responses to the VAQ. RESULTS: VAQ score was correlated (P < .01 in all
      cases) with better VA (P = -0.181), better VF (P = 0.139), worse VA (P = -0.128),
      and worse VF (P = .120). There were also correlations (P ranging from .24 to .38,
      all P values < or = .001) between patients' perception of their vision (total VAQ
      score) and each item on the HPI and CES-D. None of the clinical vision measures
      were associated with any of the CES-D items. The strongest correlation between a
      clinical measure and an item from the HPI was between worse VF and worry about
      the possibility of blindness (P = -0.114, P = .005). The odds ratio of reporting
      mood indicators and symptoms of depression increased with patients' perceptions
      of worsening visual function but not worsening VA or VF. CONCLUSIONS: In these
      newly diagnosed glaucoma patients, symptoms of depression and altered mood were
      related to worse self-reported visual function as assessed by the VAQ, but not to
      monocular clinical measures of visual function.

PMID- 17560845
TI  - Attracting and keeping new graduates.

PMID- 17560856
TI  - Cerebral aneurysm--treatment and perioperative nursing care.
AB  - A cerebral aneurysm is a weakening and saccular outpouching of a cerebral artery.
      This life threatening condition affects approximately 10 million to 15 million
      Americans annually. Perioperative nurses must be aware of the incidence, clinical
      manifestations, pathophysiology, and treatments for cerebral aneurysm. This
      article details the perioperative care of patients undergoing craniotomy for
      surgical clipping or insertion of an endovascular coil. Although endovascular
      coiling is a relatively new procedure with unknown long-term results, this
      treatment option offers patients a minimally invasive alternative to craniotomy
      with a shorter hospital stay and decreased recovery time.

PMID- 17560857
TI  - Implementing the universal protocol hospital-wide.
AB  - Beginning in July 2004, Joint Commission-accredited hospitals were required to
      adhere to the Universal Protocol for Preventing Wrong Site, Wrong Procedure,
      Wrong Person Surgery by implementing time outs and site verifications for all
      invasive procedures. At Children's Hospital Boston, Mass, this requirement
      necessitated extensive editing of the existing time out and site verification
      policy and the development of a hospital-wide implementation plan. The Hospital's
      Universal Protocol champion developed an action plan that involved including
      nurse and physician representatives from each target area; rolling out the
      policy; creating materials for advertising the policy; and formulating an
      education, monitoring, and evaluation plan.

PMID- 17560858
TI  - The wider scope of video-assisted thoracoscopic surgery.
AB  - In the past, rudimentary devices were used to look closely into the chest;
      currently, advanced video technology, computers, and high-tech electronics are
      being used to perform many surgical procedures that formerly required a large,
      open incision. The goal of video-assisted thoracoscopic surgery (VATS) is the
      same as for comparable open procedures, but it is accomplished with less pain,
      less patient morbidity, and a shorter hospital stay. In addition to evaluating
      and treating thoracic injuries, VATS has demonstrated effectiveness in detecting
      and managing many other conditions, such as pleural disease, interstitial lung
      disease, and thoracic malignancies.

PMID- 17560859
TI  - Developing a healthy OR workplace.
AB  - Innovation is required to develop a positive work environment in the OR.
      Components of a healthy or workplace identified by staff members of three
      surgical departments are quality practice standards, excellence in patient care
      systems, a functional physical environment, effective staff systems, meaningful
      role definition and clarity, and identified guidelines for teamwork. In one or,
      staff members working on a communication team developed and implemented an action
      plan to enhance respect in the OR setting.

PMID- 17560861
TI  - Encouraging patients to participate in their health care.

PMID- 17560863
TI  - Inaccuracies in selected ion monitoring determination of isotope ratios obviated
      by profile acquisition: nucleotide 18O/16O measurements.
AB  - Precise and accurate measurements of isotopologue distributions (IDs) in
      biological molecules are needed for determination of isotope effects,
      quantitation by isotope dilution, and quantification of isotope tracers employed
      in both metabolic and biophysical studies. While single ion monitoring (SIM)
      yields significantly greater sensitivity and signal/noise than profile-mode
      acquisitions, we show that small changes in the SIM window width and/or center
      can alter experimentally determined isotope ratios by up to 5%, resulting in
      significant inaccuracies. This inaccuracy is attributed to mass granularity, the
      differential distribution of digital data points across the m/z ranges sampled by
      SIM. Acquiring data in the profile mode and fitting the data to an equation
      describing a series of equally spaced and identically shaped peaks eliminates the
      inaccuracies associated with mass granularity with minimal loss of precision.
      Additionally a method of using the complete ID profile data that inherently
      corrects for "spillover" and for the natural-abundance ID has been used to
      determine 18O/16O ratios for 5',3'-guanosine bis-[18O1]phosphate and TM[18O1]P
      with precisions of approximately 0.005. The analysis protocol is also applied to
      quadrupole time-of-flight tandem mass spectrometry using [2-(18)O] arabinouridine
      and 3'-UM[18O1]P which enhances signal/noise and minimizes concerns for
      background contamination.

PMID- 17560864
TI  - Impact of metabolic syndrome on atherosclerotic burden and cardiovascular
      prognosis.
AB  - Patients with metabolic syndrome (MS) are at increased risk of cardiovascular
      atherosclerosis. The aim of this study was to evaluate the impact of MS on
      cardiovascular prognosis in context with atherosclerotic burden. A total of 811
      patients with coronary heart disease (CHD) were included and carotid and leg
      arteries were examined using sonographic methods. Patients with low (CHD only, n
      = 428, 52.8%) or high atherosclerotic burden (CHD and peripheral atherosclerosis,
      n=383, 47.2%) were compared. Patients with >or=3 of the following criteria:
      triglycerides>or=150 mg/dl, high-density lipoprotein cholesterol<40 mg/dl (men)
      and <50 mg/dl (women), body mass index>30 kg/m2, blood pressure>or=130/85 mm Hg,
      and fasting glucose>or=100 mg/dl were defined as having MS (n=349, 43.0%). Follow
      up data (median 6.7 years) were available for 807 patients (99.5%), and 175
      patients (21.7%) experienced cardiovascular events (myocardial infarction, death,
      and stroke). The presence of MS significantly increased cardiovascular events in
      patients with low and high atherosclerotic burden (low: MS yes 21.2%, MS no
      12.9%, p=0.02; high: MS yes 34.3%, MS no 26.5%, p=0.01). MS could be identified
      as an independent predictor for cardiovascular events in all patients (hazard
      ratio 1.7, 95% confidence interval 1.3 to 2.3, p<0.0001, adjusted) and patients
      with high atherosclerotic burden in particular (hazard ratio 1.8, 95% confidence
      interval 1.2 to 2.6, p=0.005, adjusted). In conclusion, MS markedly worsens the
      long-term prognosis of patients with both low and high atherosclerotic burden.
      Moreover, patients with high atherosclerotic burden and MS should be considered a
      high-risk population and treated accordingly.

PMID- 17560865
TI  - The effects of aging and physical activity on Doppler measures of diastolic
      function.
AB  - Healthy aging results in changes in Doppler measures of diastolic function. It is
      unclear whether these alterations are a specific manifestation of the aging
      process or reflect a cardiac adaptation to a more sedentary lifestyle. It was
      hypothesized that healthy, but sedentary, aging would result in slowing of
      diastolic filling and myocardial relaxation, whereas lifelong endurance training
      would prevent such changes. Doppler data were measured in young subjects and
      sedentary and fit seniors across a broad range of loading conditions. Thirteen
      sedentary healthy (70+/-4 years) and 12 fit Masters athlete (68+/-3 years)
      seniors were recruited. Twelve young healthy (32+/-9 years) subjects were used
      for comparison. Pulmonary capillary wedge pressure and Doppler variables were
      measured at the 6 loading conditions of baseline (twice), -15 and -30 mm Hg lower
      body negative pressure, and 2 levels of saline solution infusion. Doppler
      variables consisted of early and late mitral inflow velocity (E/A) ratio,
      isovolumetric relaxation time (IVRT), tissue Doppler velocities (TDI Emean), and
      propagation velocity of mitral inflow. Aging resulted in a decrease in E/A ratio
      (p<0.001), TDI Emean (p<0.001), and propagation velocity of mitral inflow
      (p<0.001) and an increase in IVRT (p=0.001). Lifelong endurance training did not
      completely prevent the changes in E/A ratio (p=0.212), IVRT (p=0.546), or
      propagation velocity of mitral inflow (p=1.00). Fit seniors were able to achieve
      E/A ratios of 1.0 during baseline and saline solution infusion. TDI Emean was
      higher in fit versus sedentary seniors at baseline (p=0.012) and during maximal
      lower body negative pressure (p=0.036), but not during saline solution infusion
      (p=0.493). In conclusion, age-associated abnormalities in Doppler measures of
      myocardial filling and relaxation are only partially minimized by lifelong
      endurance training and therefore may be more specific to the aging process than
      secondary to years of deconditioning.

PMID- 17560866
TI  - Adjusted indirect meta-analysis of aspirin plus warfarin at international
      normalized ratios 2 to 3 versus aspirin plus clopidogrel after acute coronary
      syndromes.
AB  - After acute coronary syndromes, the beneficial effect of aspirin plus clopidogrel
      (A+C) or aspirin plus dose-adjusted warfarin (A+W) compared with aspirin alone is
      well established. However, these regimens were never compared. To compare the
      risk-benefit profile of A+C versus A+W after acute coronary syndromes, major
      medical databases for randomized controlled trials comparing 1 of these combined
      approaches versus aspirin alone after an acute coronary syndrome (updated June
      2006) were searched. Evaluated end points were major adverse events [MAEs: all
      cause death, acute myocardial infarction [AMI], thromboembolic stroke, major
      bleeds, and overall risk of stroke [hemorrhagic or ischemic]). Odds ratios (ORs)
      with 95% confidence intervals (CIs) were calculated for (1) A+W versus aspirin
      alone, (2) A+C versus aspirin alone, and (3) A+W versus A+C using adjusted
      indirect meta-analysis. Thirteen studies were included, totaling 69,741 patients.
      Ten compared A+W versus aspirin alone and 3 compared A+C versus aspirin alone.
      Each combined approach yielded a significantly lower risk of MAEs, albeit an
      increased risk of major bleeds, compared with aspirin alone. No significant
      difference was found for A+W versus A+C for risk of overall MAEs, death, or AMI.
      However, A+W versus A+C was associated with a significantly lower risk of
      thromboembolic stroke (OR 0.53, 95% CI 0.31 to 0.88, number needed to treat 60)
      and all types of stroke (OR 0.58, 95% CI 0.35 to 0.94, p=0.038), but also with
      increased risk of major bleeds (OR 1.9, 95% CI 1.2 to 2.8, number needed to harm
      300). In conclusion, after an acute coronary syndrome, A+W and A+C are comparable
      in the prevention of MAEs, death, and AMI compared with aspirin alone. Allocating
      100 patients to A+W (at international normalized ratio 2 to 3) with respect to
      A+C could prevent 17 thromboembolic strokes while causing 3 major bleeds.

PMID- 17560867
TI  - Prevalence and prognosis of asymptomatic left ventricular diastolic dysfunction
      in ambulatory patients with coronary heart disease.
AB  - The association of asymptomatic left ventricular (LV) diastolic dysfunction with
      cardiovascular outcomes in ambulatory patients with coronary heart disease (CHD)
      and no history of heart failure (HF) was examined. LV diastolic HF predicts
      adverse cardiovascular outcomes. However, the prevalence and prognosis of
      asymptomatic LV diastolic dysfunction in patients with established CHD in the
      absence of clinical HF is unknown. Six hundred ninety-three patients with stable
      CHD, normal systolic function (LV ejection fraction>or=50%), and no history of HF
      were evaluated. Echocardiography was used to classify LV diastolic function, and
      Cox proportional hazards models were used to evaluate the association of LV
      diastolic dysfunction with cardiovascular outcomes during 3 years of follow-up.
      Of 693 subjects with normal systolic function and no history of HF, 455 (66%) had
      normal LV diastolic function, 166 (24%) had mild LV diastolic dysfunction, and 72
      (10%) had moderate to severe LV diastolic dysfunction. After multivariable
      adjustment, the presence of moderate to severe LV diastolic dysfunction was
      strongly predictive of incident hospitalization for HF (hazard ratio 6.3, 95%
      confidence interval 2.4 to 16.1, p=0.0003) and death from heart disease (HR 3.9,
      95% confidence interval 1.0 to 14.8, p=0.05). In conclusion, moderate to severe
      LV diastolic dysfunction was present in 10% of patients with stable CHD with
      normal ejection fraction and no history of HF and predicts subsequent
      hospitalization for HF and death from heart disease. Patients with asymptomatic
      LV diastolic dysfunction may benefit from more aggressive therapy to prevent or
      delay the development of HF.

PMID- 17560868
TI  - Effect of estradiol-drospirenone hormone treatment on myocardial perfusion
      reserve in postmenopausal women with angina pectoris.
AB  - Recent randomized clinical studies failed to show cardiovascular protection with
      postmenopausal hormone therapy (HT), instead raising widespread concerns about
      possible increased cardiovascular risk. However, these studies primarily assessed
      the combination of conjugated equine estrogen and medroxyprogesterone acetate,
      which is suspected to abolish the beneficial effects of estrogen on the
      microcirculation. This preliminary study evaluated the effects of HT combining
      17beta-estradiol (E2) with a new progestin, drospirenone, on myocardial perfusion
      reserve, a surrogate marker of coronary function. In this double-blind randomized
      study, 56 postmenopausal women with angina pectoris received oral E2 1 mg plus
      drospirenone 2 mg or placebo for 6 weeks. Myocardial perfusion reserve was
      measured using radioactive oxygen-labeled water and positron emission tomography
      before and after therapy. Myocardial perfusion reserve increased significantly in
      the E2-drospirenone group after 6 weeks versus placebo (p<0.0008). Mean
      myocardial perfusion reserve increased from 4.83 at baseline to 5.13 after 6
      weeks in the E2-drospirenone group (n=27), but decreased from 4.84 to 4.13 in the
      placebo group (n=29). No significant side effects were observed with E2
      drospirenone. A larger trial is needed to investigate whether myocardial
      perfusion improvements will be sustained and translate into a clinical benefit in
      postmenopausal women at risk of coronary heart disease. In conclusion, E2
      drospirenone HT for 6 weeks has favorable effects on myocardial function in
      postmenopausal women with angina pectoris. These data suggest that drospirenone
      has the desired progestin actions on the endometrium, but does not abolish the
      beneficial effects of estradiol on cardiac microcirculation.

PMID- 17560869
TI  - Size of coronary artery in a myocardial bridge compared with adjacent nontunneled
      left anterior descending coronary artery.
AB  - Patients with myocardial bridging (MB) may experience myocardial ischemia.
      Coronary stenting was reported to serve as an effective interventional approach
      to improve symptoms in selected patients with MB, but is related to high risk of
      coronary perforation. The aim of this study is to investigate vessel area in the
      myocardial bridge segment in comparison to that of adjacent segments proximal and
      distal to MB using intravascular ultrasound. A total of 81 myocardial bridge
      segments, characterized by a half-moon-shaped echolucent zone surrounding the
      intramural artery, were found in 78 patients using intravascular ultrasound. The
      cross-sectional area within the external elastic membrane and minimum and maximum
      diameters in the myocardial bridge segment and adjacent reference vessel segments
      were measured. Diastolic cross-sectional area within the external elastic
      membrane in the myocardial bridge segment was significantly smaller than that in
      adjacent segments both proximal and distal to MB (5.48+/-2.59 vs 9.40+/-3.48 and
      7.22+/-2.87 mm2, respectively, both p<0.001). Maximum vessel diameter in the
      myocardial bridge segment during diastole was also smaller than that in the
      segment distal to MB (2.74+/-0.61 vs 3.12+/-0.59 mm, p<0.001). In conclusion, our
      study showed that vessel area in the myocardial bridge segment was smaller than
      that in adjacent segments proximal and distal to MB.

PMID- 17560870
TI  - Diagnostic performance of 64-channel multislice computed tomography in assessment
      of significant coronary artery disease in symptomatic subjects.
AB  - The recent development of 64-channel multislice computed tomography (MSCT) has
      resulted in noninvasive coronary artery imaging improvement. This study was
      conducted to determine the accuracy of 64-slice MSCT in a relatively unselected
      group of 143 patients with presentations suggestive of coronary artery disease,
      including those with unstable angina pectoris, who underwent both coronary
      computed tomographic angiography and invasive coronary angiography. No arrhythmia
      was considered an exclusion criterion except for atrial fibrillation or frequent
      extrasystoles. In patients with fast heart rates, a beta blocker was administered
      orally. Data were obtained using electrocardiography gated 64-slice MSCT.
      Computed tomographic angiography and invasive coronary angiography findings of
      each coronary segment were compared to determine the sensitivity, specificity,
      positive predictive value, and negative predictive value of MSCT in the detection
      of their normalcy or insignificant (<50% diameter decrease) stenosis versus
      significant (>or=50% diameter decrease) stenosis or total occlusion. In per
      patient assessment, the calculated sensitivity, specificity, positive predictive
      value, and negative predictive value of MSCT were 96%, 67%, 91%, and 83%,
      respectively. These values in per-artery evaluation were 94%, 94%, 87%, and 97%,
      and corresponding values in per-segment analysis were 92%, 97%, 77%, and 99%,
      respectively. In conclusion, computed tomographic angiography has high diagnostic
      performance in the assessment of significant coronary artery disease in most
      patients in a daily routine practice, including those presenting with unstable
      angina pectoris symptoms.

PMID- 17560871
TI  - Yield of early rest and stress myocardial perfusion single-photon emission
      computed tomography and electrocardiographic exercise test in patients with
      atypical chest pain, nondiagnostic electrocardiogram, and negative biochemical
      markers in the emergency department.
AB  - There are no studies in which diagnostic yield of early rest myocardial perfusion
      gated single-photon emission computed tomography (SPECT), electrocardiographic
      exercise testing, and stress SPECT were compared in patients with atypical chest
      pain, nondiagnostic electrocardiograms (ECGs), and negative markers of myocardial
      damage in the emergency department. A prospective study of 96 patients who
      presented with atypical chest pain and nondiagnostic ECG, but without elevated
      markers of necrosis, was performed. All underwent rest gated SPECT using
      technetium-99m methoxyisobutyl isonitrile within 6 hours after pain subsided
      followed by an electrocardiographic exercise test to obtain stress-rest SPECT
      images. After 1 year, there were no deaths and coronary artery disease was
      confirmed in only 5 patients. Negative predictive values of the 3 techniques were
      high (99%, 96%, and 100%, respectively), but positive predictive values were low
      (27%, 22%, and 14%, respectively). Sensitivities of early SPECT (80%) and stress
      SPECT (100%) were higher than for the electrocardiographic exercise test (40%).
      In conclusion, in patients with atypical chest pain, nondiagnostic ECG, and
      negative biochemical markers, negative predictive values of the 3 tests analyzed
      are very high. The sensitivity of radionuclide tests is higher, but their
      widespread use does not appear warranted because their positive predictive value
      and incidence of complications is low.

PMID- 17560872
TI  - Usefulness of contrast echocardiography for assessment of left ventricular
      thrombus after acute myocardial infarction.
AB  - Fifty consecutive patients referred to a coronary care unit for acute anterior
      myocardial infarction with ST-segment elevation underwent coronary arteriography,
      left ventricular (LV) angiography, and revascularization. Transthoracic
      echocardiography was systematically performed using fundamental imaging, second
      harmonic imaging, and contrast agents to assess the LV chamber. Six patients
      (12%) presented with a confirmed LV mural thrombus. Thirty-five percent of
      patients with time to revascularization>3 hours presented with an LV mural
      thrombus versus 0 patients with time to revascularization<or=3 hours (p=0.003).
      The most accurate method of detecting LV mural thrombus was contrast
      echocardiography regardless of physician experience. No patient with a
      misdiagnosis of thrombus had an optimal acoustic window using fundamental imaging
      or second harmonic imaging. In conclusion, patients presenting with acute
      anterior myocardial infarction could benefit from contrast echocardiography for
      assessment of LV mural thrombus when acoustic windows are suboptimal and time to
      revascularization is >3 hours.

PMID- 17560873
TI  - Relation of myocardial blush grade to microvascular perfusion and myocardial
      infarct size after primary or rescue percutaneous coronary intervention.
AB  - Angiographic myocardial blush grade (MBG) is a potent predictor of long-term
      outcome after percutaneous treatment of myocardial infarction, yet little is
      known regarding the underlying pathophysiologic features. The relation between
      MBG and cardiovascular magnetic resonance (CMR)-defined amounts of necrosis and
      microvascular obstruction was examined in 27 patients. Another powerful
      prognostic indicator, ST-segment resolution>70%, was correlated with other
      predictors. Increasing MBG was associated (p=0.001) in a linear fashion (p<0.001)
      with less microvascular obstruction using CMR, whereas the inverse relation with
      amount of necrosis, although significant (p=0.043), was nonlinear (p=0.36). ST
      resolution was not correlated with either MBG or CMR parameters. In conclusion,
      MBG is mainly influenced by microvascular patency and is less dependent on the
      amount of muscle necrosis, and the common practice of including MBG 2 and 3 into
      a single "patent microcirculation" category might not be justified. Moreover, the
      mechanisms of ST resolution should be searched for at the cellular level.

PMID- 17560874
TI  - Impact of admission hyperglycemia and diabetes mellitus on short- and long-term
      mortality after acute myocardial infarction in the coronary intervention era.
AB  - The influence of admission hyperglycemia and diabetes on short- and long-term
      mortality of patients with acute myocardial infarction (AMI) in the percutaneous
      coronary intervention (PCI) era was investigated. From 1996 to 2003, a total of
      802 consecutive patients with AMI underwent coronary angiography. Primary PCI was
      performed in 724 patients (90%). Three-year mortality curves were constructed
      using the Kaplan-Meier method. Cox proportional hazard regression was used to
      identify independent predictors of 30-day mortality and mortality from 30 days to
      3 years. There were 261 patients with admission hyperglycemia (admission
      glucose>or=11.1 mmol/L) and 212 patients with diabetes. Admission hyperglycemia
      was associated with a significantly higher 30-day mortality rate (8.4% vs 2.4%,
      p<0.001). However, there was no significant difference in 30-day mortality rates
      between diabetic and nondiabetic patients (5.7% vs 3.9%, p=0.29). Conversely,
      diabetes significantly increased mortality from 30 days to 3 years (10.0% vs
      5.5%, p=0.03), but admission hyperglycemia did not (8.4% vs 5.9%, p=0.19).
      Multivariate analysis showed that hyperglycemia was an independent predictor of
      30-day mortality (odds ratio [OR] 1.71, 95% confidence interval [CI] 1.13 to
      2.61, p=0.01), but diabetes was not (OR 0.84, 95% CI 0.55 to 1.27, p=0.42).
      Diabetes was independently associated with mortality from 30 days to 3 years (OR
      1.43, 95% CI 1.02 to 1.97, p=0.04), but hyperglycemia had a neutral effect (OR
      0.98, 95% CI 0.70 to 1.36, p=0.92). In conclusion, in the PCI era, admission
      hyperglycemia was associated with short-term mortality, whereas diabetes
      increased long-term mortality after convalescence in patients with AMI. Admission
      hyperglycemia and diabetes should be treated as 2 distinct disease states.

PMID- 17560875
TI  - Impact of time to treatment on myocardial reperfusion and infarct size with
      primary percutaneous coronary intervention for acute myocardial infarction (from
      the EMERALD Trial).
AB  - The impact of time to treatment on outcomes after primary percutaneous coronary
      intervention (PCI) is controversial, and there are few data about time to
      treatment and infarct size. The EMERALD trial randomly assigned 501 high-risk
      patients with ST-elevation myocardial infarction undergoing primary PCI to
      stenting with or without GuardWire (Medtronic, Santa Rosa, California) distal
      protection. Infarct size using sestamibi imaging at 5 to 14 days and clinical
      outcomes were examined by time to treatment. There were no differences in
      outcomes between distal protection and control patients. Shorter time to
      reperfusion (<2 vs 2 to 3 vs >3 to 4 vs >4 hours) was associated with smaller
      infarct size (2% vs 9% vs 12% vs 11%, p=0.026), trends for better myocardial
      blush (p=0.08), and lower 6-month mortality rates (0% vs 0% vs 2.4% vs 5.3%,
      p=0.06). Incremental delays in reperfusion after 2 hours had little impact on
      infarct size. Shorter time to reperfusion impacted on infarct size in patients
      with anterior infarction (0% vs 17% vs 20.5% vs 30.5%, p=0.026), but not
      nonanterior infarction (3% vs 7% vs 7.5% vs 10%, p=0.23, p=0.022 for
      interaction). In conclusion, very early reperfusion with primary PCI is
      associated with smaller infarct size and has a much greater impact in anterior
      versus nonanterior infarction. Incremental delays in reperfusion after 2 hours
      have less effect on infarct size. These data have implications regarding the
      triage of patients for primary PCI.

PMID- 17560876
TI  - Association of prerandomization anticoagulant switching with bleeding in the
      setting of percutaneous coronary intervention (A REPLACE-2 analysis).
AB  - The REPLACE-2 trial of patients who underwent urgent or elective percutaneous
      coronary intervention (PCI) demonstrated a significantly lower bleeding risk with
      bivalirudin plus provisional glycoprotein IIb/IIIa inhibitor compared with
      unfractionated heparin with planned glycoprotein IIb/IIIa inhibitor. The goal of
      this analysis was to evaluate whether a hazard existed when unfractionated
      heparin or low-molecular-weight heparin was administered before study medication
      in the REPLACE-2 trial. The REPLACE-2 trial randomized 6,010 patients undergoing
      PCI to receive bivalirudin plus provisional glycoprotein IIb/IIIa inhibitor or
      unfractionated heparin plus planned glycoprotein IIb/IIIa inhibitor. The present
      study compared bleeding among patients treated with or without antithrombin
      therapy in the 48 hours before study treatment. Among patients treated with
      bivalirudin, there was no difference in protocol-defined major or minor bleeding,
      bleeding according to Thrombolysis In Myocardial Infarction criteria, or
      noncoronary artery bypass graft blood transfusions between the patients treated
      with versus without antithrombin therapy (p=NS). However, in patients treated
      with unfractionated heparin plus planned glycoprotein IIb/IIIa inhibitor, there
      was a significant increase in the composite of protocol-defined major or minor
      bleeding and in noncoronary artery bypass graft blood transfusions (p<0.05 for 3
      way comparison vs no unfractionated heparin and for 2-way comparisons of no
      unfractionated heparin vs unfractionated heparin or low-molecular-weight
      heparin). In conclusion, in patients treated with bivalirudin, pretreatment with
      antithrombin therapy was not associated with increased bleeding. In contrast,
      among patients randomized to receive unfractionated heparin and planned
      glycoprotein IIb/IIIa, pretreatment with antithrombin therapy was associated with
      increased protocol-defined composite major or minor bleeding and increased need
      for transfusion.

PMID- 17560877
TI  - Six-month clinical and angiographic results of a dedicated drug-eluting stent for
      the treatment of coronary bifurcation narrowings.
AB  - Percutaneous intervention for coronary bifurcation lesions has been associated
      with increased clinical complication rates compared with nonbifurcation lesions,
      primarily as a result of restenosis. Therefore, there is a need for new
      techniques. The purpose of this study was to evaluate a new drug-eluting stent
      and implantation technique for the treatment of de novo coronary bifurcation
      lesions. The Axxess Plus trial was a prospective multicenter single-arm study
      that enrolled 139 patients. Each patient received a self-expanding, conically
      shaped nickel-titanium Axxess Plus biolimus A9-eluting stent at the level of the
      carina. Depending on the lesion anatomy, additional nonstudy stents were placed
      distally if necessary. Clinical and angiographic follow-up were scheduled at 6
      months after the procedure. The overall rate of target lesion revascularization
      was 7.5% at 6 months. A mean of 2.4 stents were implanted per patient; 51.2% of
      patients received a stent to the side branch, 29.4% received balloon angioplasty
      only, and 20.6% of side branches were not treated. In-stent late loss in the
      Axxess stents was 0.09 mm. Incidences of angiographic in-stent restenosis were
      7.1% in the parent vessel stents and 9.2% in the group receiving stents in the
      side branch (7.9% excluding bare metal stents placed distal to the Axxess stent),
      compared with 25% for balloon angioplasty treatment and 12% for no treatment.
      Late stent thrombosis was observed in 3 cases, 2 of which were associated with
      confirmed premature cessation of antiplatelet therapy. In conclusion, the Axxess
      Plus conical stent effectively treats bifurcation lesions alone or in conjunction
      with other drug-eluting stents.

PMID- 17560878
TI  - The editor's roundtable: high-density lipoprotein cholesterol.

PMID- 17560879
TI  - Comparison of effects of ezetimibe/simvastatin versus simvastatin versus
      atorvastatin in reducing C-reactive protein and low-density lipoprotein
      cholesterol levels.
AB  - The lowering effects of ezetimibe/simvastatin combination therapy on low-density
      lipoprotein (LDL) cholesterol and high-sensitivity C-reactive protein (CRP) were
      compared with those of simvastatin or atorvastatin monotherapy in a large cohort
      of patients with primary hypercholesterolemia. To compare ezetimibe/simvastatin
      with simvastatin, data were combined from 3 identical, prospective 12-week trials
      in which patients were randomized to receive placebo; ezetimibe 10 mg; ezetimibe
      10 mg added to simvastatin 10, 20, 40, or 80 mg; or simvastatin 10, 20, 40, or 80
      mg. To compare ezetimibe/simvastatin with atorvastatin, data were analyzed from a
      phase III double-blind, active-controlled study in which patients were randomized
      equally to receive ezetimibe/simvastatin 10/10, 10/20, 10/40, or 10/80 mg or
      atorvastatin 10, 20, 40, or 80 mg for 6 weeks. When averaged across doses,
      ezetimibe/simvastatin produced significantly greater reductions compared with
      simvastatin alone in LDL cholesterol (52.5% vs 38.0%, respectively) and CRP
      levels (31.0% vs 14.3%, respectively). At each individual simvastatin dose, co
      administration with ezetimibe produced significant further CRP reductions versus
      simvastatin alone. Ezetimibe/simvastatin was significantly more effective at
      lowering LDL cholesterol than atorvastatin when pooled across doses (53.4% vs
      45.3%, respectively) and in each milligram-equivalent dose comparison. Reductions
      in CRP of similar magnitude were observed with ezetimibe/simvastatin and
      atorvastatin when averaged across doses and at each milligram-equivalent statin
      dose comparison. In conclusion, the lipid-modulating and anti-inflammatory
      effects of ezetimibe/simvastatin provide additional benefits not realized by
      statin monotherapy alone.

PMID- 17560880
TI  - Effect of simvastatin (80 mg) on coronary and abdominal aortic arterial calcium
      (from the coronary artery calcification treatment with zocor [CATZ] study).
AB  - We tested the hypothesis that, compared with placebo, simvastatin would reduce
      the progression of coronary artery calcium (CAC) and abdominal aortic calcium
      (AAC) levels in participants asymptomatic for vascular disease. Total CAC and AAC
      were measured with multidetector cardiac computed tomography. Inclusion criteria
      were a CAC score of >or=50 Agatston units, high-density lipoprotein (HDL)
      cholesterol level<or=50 mg/dl, low-density lipoprotein (LDL) cholesterol level
      between 100 and 160 mg/dl, and >or=2 other risk factors. Diabetes and history of
      vascular disease were exclusion criteria. Participants were randomized to receive
      80 mg simvastatin (n=40) or matching placebo (n=40) for 12 months. Lipids were
      measured at 3-month intervals, and CAC and AAC measurements were repeated at 6
      and 12 months. Total cholesterol, triglycerides, and LDL decreased significantly
      with simvastatin treatment (p<0.0001 for all comparisons, adjusted for baseline
      levels), whereas lipids remained unchanged for subjects randomized to receive
      placebo. Total CAC volume increased from baseline in both treatment groups. For
      subjects in the active treatment group, CAC volume increased by 9%, whereas in
      the placebo group, plaque volume increased by 5% (p=0.12 for treatment effect).
      AAC volume also increased in both treatment groups (p=0.15 for treatment effect).
      In conclusion, simvastatin treatment does not reduce progression of CAC or AAC
      compared with placebo.

PMID- 17560881
TI  - Measuring and treating serum lipids in patients in a chest pain observation unit.
AB  - We evaluated opportunities to initiate statin therapy in 574 consecutive subjects
      admitted to a chest pain observation unit (CPOU). Ten-year Framingham risk scores
      were retrospectively calculated for all patients according to the National
      Cholesterol Education Program and Adult Treatment Panel III 2001 recommendations.
      Subjects were then stratified according to (1) recommendations for initiation of
      a lipid-lowering medication and (2) whether they received lipid-lowering drug
      therapy at discharge. Of 574 subjects, we excluded 50 with previously established
      coronary heart disease or who were already taking a statin medication on
      presentation, 23 with missing data, and 80 who did not have a low-density
      lipoprotein (LDL) measurement at admission. Of the remaining 421 subjects, the
      mean age was 47 years, 40% were men, 57% were white, 31% had hypertension, 27%
      were current smokers, and 6% had diabetes. Ten-year risk calculation classified
      47% (n=199) at low risk (<2 risk factors), 32% (n=134) at moderate risk (>or=2
      risk factors and <10% risk), 11% (n=48) at moderate-high risk (10% to 20% risk),
      and 10% (n=40) at high risk (>20% risk). Of the entire cohort, 23% of subjects
      (n=96) had hypercholesterolemia, of which 52% (n=50) met indications for
      initiation of lipid-lowering medication. Only 6% of patients with an indication
      for treatment (n=3) were prescribed a lipid-lowering medication on discharge,
      leaving 94% (n=47) untreated for their hypercholesterolemia. In conclusion,
      patients admitted to a CPOU have a high prevalence of hypercholesterolemia, and
      therefore, an increased long-term risk for cardiovascular events. In addition to
      their primary role, CPOUs should focus on primary prevention and reduction of
      long-term risk.

PMID- 17560882
TI  - A comparative study of the efficacy and safety of procainamide versus propafenone
      versus amiodarone for the conversion of recent-onset atrial fibrillation.
AB  - The appropriate treatment for the restoration of sinus rhythm in patients with
      atrial fibrillation (AF) of recent onset is still the subject of controversy. In
      this prospective, randomized, single-blind, placebo-controlled clinical study, we
      investigated the effectiveness and safety of procainamide, propafenone, and
      amiodarone, administered intravenously, for the conversion of recent-onset AF. We
      enrolled 362 consecutive patients (183 men; age 34 to 86 years; mean 65+/-10)
      with AF duration of no >48 hours. Of these patients, 89 were given procainamide,
      91 propafenone, 92 amiodarone, and 90 placebo. Treatment was considered
      successful if conversion to sinus rhythm was achieved within the 24-hour study
      period. Baseline clinical characteristics were similar in the 4 groups. The
      treatment was successful in 61 of the 89 patients who received procainamide
      (68.53%; median time 3 hours), 73 of the 91 patients who received propafenone
      (80.21%; median time 1 hour), 82 of the 92 patients who received amiodarone
      (89.13%; median time 9 hours), and 55 of the 90 patients who received placebo
      (61.11%; median time 17 hours; p<0.05 for all medicated groups vs placebo; p<0.05
      for amiodarone and propafenone vs procainamide). In conclusion, all 3
      medications, when administered intravenously, are effective in the restoration of
      sinus rhythm in recent-onset AF. Amiodarone and propafenone are more effective
      whereas procainamide and propafenone are faster.

PMID- 17560883
TI  - Meta-analysis of magnesium therapy for the acute management of rapid atrial
      fibrillation.
AB  - The profile of electrophysiologic effects of magnesium on the heart suggests that
      magnesium might be effective in the treatment of atrial fibrillation (AF) in
      terms of rhythm and rate control. We aimed to investigate the efficacy of
      magnesium administration in the acute treatment of rapid AF. Randomized
      controlled trials comparing intravenous magnesium versus placebo or
      antiarrhythmic agents for the acute management of rapid AF were included. Nine
      electronic databases were searched for relevant trials from the earliest possible
      dates through June 2005, as were abstract books from 8 cardiovascular meetings
      held in the past 10 years. We analyzed all outcomes using a fixed-effect model
      because of the low number of trials in each comparison. The results were
      expressed as relative risks (RRs) or odds ratios (ORs) for dichotomous outcomes
      and weighted mean differences for continuous outcomes, along with their 95%
      confidence intervals (CIs). Data were pooled for 4 trials (n=303) and 8 trials
      (n=476), respectively, for rate control (<100 beats/min) and rhythm control.
      Magnesium was effective in achieving rate control (OR 1.96, 95% CI 1.24 to 3.08)
      or rhythm control (OR, 1.60, 95% CI 1.07 to 2.39). An overall response was
      achieved in 86% and 56% of patients in the magnesium and control groups,
      respectively (OR 4.61 95% CI 2.67 to 7.96). Time to response (in hours) was
      significantly shorter in the magnesium group (weighted mean difference, -6.98;
      95% CI -9.27 to -4.68). The risk of having a major adverse effect in the
      magnesium group was similar to that in the placebo group (RR 0.85, 95% CI 0.44 to
      1.61). In conclusion, the present meta-analysis of published data suggests that
      intravenous magnesium administration is an effective and safe strategy for the
      acute management of rapid AF.

PMID- 17560884
TI  - Clinical and echocardiographic markers of mortality risk in patients with atrial
      fibrillation.
AB  - Atrial fibrillation (AF) is independently associated with increases in
      cardiovascular and all-cause mortality. Although cardiovascular co-morbidities
      predict stroke risk in AF, their relation with mortality has not been well
      described. To identify clinical and echocardiographic markers of mortality in
      patients with AF, 524 patients with AF underwent transesophageal echocardiography
      from August 2000 to March 2005. Clinical risk factors for systemic
      thromboembolism were determined for each patient. A CHADS2 (congestive heart
      failure, hypertension, age>75 years, diabetes, and previous stroke or transient
      ischemic attack) score ranging from 0 to 6 was calculated for each patient.
      Transesophageal echocardiographic reports were reviewed for the presence of left
      atrial spontaneous echocardiographic contrast, left atrial thrombus, the left
      ventricular ejection fraction, aortic arch atheroma, and the presence and
      severity of mitral regurgitation. Mortality data were obtained from the Social
      Security Death Master File. Univariate and multivariate models were structured to
      assess which variables predicted mortality. In a multivariate model, a history of
      heart failure, age>75 years, the absence of systemic anticoagulation with
      warfarin, the presence of left atrial spontaneous echocardiographic contrast, and
      greater than moderate mitral regurgitation were independent predictors of
      mortality. Increasing CHADS2 score was also an independent predictor of
      mortality. A CHADS2 score of 5 or 6 was associated with a >50-fold increase in
      mortality compared with patients with CHADS2 scores of 0. In conclusion, a
      history of heart failure, age>or=75 years, the absence of chronic oral
      anticoagulation, a CHADS2 score>0, and greater than moderate mitral regurgitation
      are independent predictors of mortality in patients with AF.

PMID- 17560885
TI  - A novel mutation in human ether-a-go-go-related gene, alanine to proline at
      position 490, found in a large family with autosomal dominant long QT syndrome.
AB  - Long-QT syndrome is a rare disease characterized by prolonged ventricular
      repolarization. The clinical presentation of long-QT syndrome is the occurrence
      of syncope, seizures, or cardiac arrest in young patients. Previous studies have
      demonstrated locus heterogeneity, with causative mutations reported in >or=8
      different genes, including the human ether-a-go-go-related gene. This study was
      conducted in 26 members of a 4-generation family with long-QT syndrome. The
      proband was a 14-year-old female patient referred to the emergency department for
      the evaluation of recurrent syncope associated with a prolonged QT interval on
      electrocardiography at rest. There was a family history of sudden death in a 27
      year-old woman. Sequencing of the entire coding regions of the human ether-a-go
      go-related gene and the intron and exon boundaries of the proband identified a
      single base-pair substitution (guanine to cytosine at nucleotide 1468). This
      mutation resulted in a novel missense mutation, alanine to proline at position
      490 (Ala490Pro), in the inner loop of the S2 and S3 domains. The proband was
      heterozygous for the Ala490Pro mutation. To address whether the mutational change
      detected in the patient would be a polymorphism, 100 control subjects from the
      same ethnical background were investigated. None showed the Ala490Pro
      substitution. Of 26 family members, 9 were mutation carriers, and none had normal
      electrocardiographic results. The penetrance of this pedigree was assumed to be
      100%. In conclusion, the Ala490Pro mutation of the human ether-a-go-go-related
      gene is a rare, novel mutation that was inherited in this family, leading to
      Romano-Ward syndrome with complete penetrance.

PMID- 17560886
TI  - Effect of medical therapy for heart failure on segmental myocardial function in
      patients with ischemic cardiomyopathy.
AB  - The adjustment of medications and dosages to the needs of individual patients
      with heart failure is mostly intuitive, but even when their effect on global
      myocardial function is measured by classic indexes, their effect on segmental
      function is overlooked. This study was conducted to assess the feasibility of
      using echocardiographic myocardial strain imaging to evaluate the effect of
      medication on global and segmental function in 21 ambulatory patients with heart
      failure (mean age 65+/-11 years) who had echocardiographic studies performed
      before and 2 hours after ingesting their regular morning medications. The
      ejection fraction, global and regional strain, and time to regional peak strain
      were compared between the 2 examinations. Medication induced no significant
      changes in mean ejection fraction (28.6+/-7.8% to 27.5+/-9.9%) and mean global
      strain (-9.5+/-3.6% to -9.8+/-3.2%). Changes in segmental strain depended on
      baseline function: normal segments (peak strain more negative than -12%)
      deteriorated (-15.5+/-2.7% to -13.7+/-4.6%, p<0.0001), but dysfunctional segments
      (peak strain less negative than -8%) improved (-5.3+/-2.0% to -7.4+/-4.3%,
      p<0.0001). Medication also improved segmental synchronization: average time to
      peak strain of segments in which peak strain was attained before aortic valve
      closure increased (325+/-69 to 375+/-100 ms, p<0.0001), but that of segments with
      postsystolic shortening at baseline decreased (451+/-93 to 435+/-93 ms, p<0.006).
      Thus, the time interval between time to peak strain of segments with systolic and
      post-systolic shortening at baseline was halved after medication. In conclusion,
      medications for heart failure induced an increase in the echocardiographically
      determined peak strain of myocardial segments with impaired function at baseline
      but decreased the peak strain of normally contracting segments. Medications also
      improved the synchronization of myocardial contraction. Neither the global
      ejection fraction nor global strain reflected these changes. Thus, medication
      tended to improve the homogeneity of left ventricular contraction.

PMID- 17560887
TI  - Relation of etiology of heart failure (ischemic versus nonischemic) before
      transplantation to delayed pulmonary oxygen uptake kinetics after heart
      transplantation.
AB  - The effect that pretransplantation heart failure cause has on pulmonary oxygen
      uptake (VO2p) kinetics and peak aerobic power (VO2peak) in heart transplant
      recipients (HTRs) has not been studied. We examined VO2p kinetics and VO2peak in
      HTRs with previous ischemic heart failure (I-HTRs; n=16, mean age 64+/-6 years)
      or nonischemic heart failure (NI-HTRs; n=13, mean age 50+/-12 years). HTRs
      performed an incremental exercise (VO2peak) test and a constant work rate
      submaximal exercise (VO2p kinetics) test. A monoexponential model was used to
      determine the phase II VO2p time constant (tau). Phase II VO2p tau was slower in
      I-HTRs (49+/-10 seconds) than in NI-HTRs (34+/-10 seconds) (p<0.001). No
      significant difference was found between I-HTRs and NI-HTRs for VO2peak (19.0+/
      6.4 vs 23.0+/-8.2 ml.kg-1.min-1, respectively), change in heart rate from rest to
      steady-state exercise (11+/-8 vs 9+/-9 beats.min-1, respectively), or peak
      exercise heart rate (140+/-22 vs 144+/-22 beats.min-1, respectively). In
      conclusion, the prolonged phase II VO2p tau in I-HTRs compared with NI-HTRs
      suggests that the magnitude of alteration in VO2p kinetics after heart
      transplantation may be dependent on previous heart failure cause.

PMID- 17560888
TI  - Mutations in the genes for sarcomeric proteins in Japanese patients with onset
      sporadic hypertrophic cardiomyopathy after age 40 years.
AB  - This study was conducted to assess the hypothesis that mutations in the genes for
      sarcomeric proteins are the molecular cause for older-onset sporadic hypertrophic
      cardiomyopathy (HC) in Japanese patients. Molecular genetic approaches have
      demonstrated that familial HC is caused by mutations in genes encoding sarcomeric
      proteins. Recent studies have shown that sarcomeric gene mutations can also be a
      molecular cause of older-onset and/or sporadic HC. However, genetic studies to
      date have examined only a limited number of older Caucasian patients with HC.
      Clinical evaluations were performed in patients with HC onset after 40 years of
      age, and the sequence encoding the beta-cardiac myosin heavy chain, cardiac
      troponin T, cardiac troponin I, cardiac myosin binding protein-C, myosin
      ventricular regulatory light chain, and myosin ventricular essential light chain
      genes was analyzed. When a putative mutation was identified, clinical evaluations
      and genetic studies were subsequently performed on all first-degree relatives.
      Forty-one patients with sporadic HC onset after 40 years of age (31 men, 10
      women; mean age 63+/-10 years at the time of study) were studied. Four novel
      missense mutations in the cardiac myosin binding protein-C gene (arginine to
      tryptophan at codon 160, glutamic acid to lysine at codon 334, glycine to
      arginine at codon 507, and threonine to methionine at codon 1,046) and a
      previously reported missense mutation in the beta-cardiac myosin heavy chain gene
      (arginine to histidine at codon 663) were identified in 5 of the 41 patients. No
      family members carried these mutations or had clinical evidence of HC. In
      conclusion, mutations in the cardiac myosin binding protein-C are the most common
      cause of older-onset sporadic HC in Japan.

PMID- 17560889
TI  - Usefulness of percutaneous left ventricular assist device as a bridge to recovery
      from myocarditis.
AB  - The TandemHeart percutaneous left ventricular assist device is a left atrial-to
      femoral artery bypass system that can be implanted percutaneously within 30
      minutes and provides active circulatory support. The TandemHeart has been used
      mainly for temporary hemodynamic assistance during high-risk coronary
      interventions and postcardiotomy heart failure. This report describes initial
      experience with this device as a successful bridge to cardiac recovery in 3
      patients with acute myocarditis. All patients presented with severe cardiogenic
      shock (mean cardiac index 1.1 L/min/m2), and end-organ perfusion could not be
      maintained despite intra-aortic balloon counterpulsation and the maximal use of
      vasopressive agents. The patients were successfully bridged to myocardial
      recovery with the TandemHeart (mean duration of support 5 days, range 2 to 8).
      The only complication was a short episode of ventricular fibrillation during
      device placement in 1 patient, which did not result in any morbidity or
      mortality. All patients were discharged home (mean duration of stay 15 days). In
      conclusion, the TandemHeart proved to be a safe and effective bridge to
      myocardial recovery in these patients with acute myocarditis.

PMID- 17560890
TI  - Comparison of late post-operative cardiopulmonary responses in the Fontan versus
      ventricular septation for double-inlet left ventricular repair.
AB  - Ventricular septation (VS) and the Fontan procedure are alternatives for
      definitive repair in patients with double-inlet left ventricle; although VS is
      theoretically preferable, the current preference in practice is the Fontan
      procedure. However, the long-term outcomes of both procedures remain unclear. To
      address this issue, cardiopulmonary responses during exercise were measured in
      patients with double-inlet left ventricle, and the impact of the type of
      procedure performed, Fontan or VS, on long-term exercise capacity and late
      postoperative clinical profiles was assessed. Fourteen post-Fontan patients (mean
      age 17+/-6 years) and 13 VS patients (mean age 19+/-4 years) underwent exercise
      testing. Of the 13 VS patients, 5 required atrioventricular valve replacement
      (AVVR), and 7 required pacemaker implantation. Although no difference in peak
      oxygen uptake was found between the VS and Fontan patients, peak oxygen uptake
      was higher in VS patients without AVVR (30+/-8 ml/kg/min) than in VS patients
      with AVVR (19+/-1 ml/kg/min) and Fontan patients (22+/-6 ml/kg/min) (p<0.01).
      There was no significant difference in peak oxygen uptake between the VS patients
      with and without pacemaker implantation (p=0.09). The clinical profiles of the VS
      and Fontan patients were similar in terms of medication and freedom from
      tachyarrhythmias or reoperations during the follow-up period. In conclusion, the
      data suggest that VS without AVVR provides excellent future exercise capacity in
      selected patients with double-inlet left ventricle.

PMID- 17560891
TI  - Cardiac function before and after surgery for pectus excavatum.
AB  - A 2006 meta-analysis concluded that thoracic surgery for pectus excavatum (PE)
      significantly improves cardiovascular function. However, that analysis was flawed
      by a high level of heterogeneity in the outcomes and inappropriate methods in 5
      of the 8 publications analyzed. Therefore, a search of the published research
      from 1965 to the present was conducted, and only 5 publications were found that
      reported studies of cardiac function before and after operation, including 118
      patients and 82 unoperated controls. Cardiac function was studied most frequently
      by echocardiography, despite the limitations imposed by the abnormal anatomy of
      pectus excavatum, but only studies that did not report cardiac or left
      ventricular dimensions or output were excluded. Studies using indirect estimates
      on the basis of oxygen pulse, which depends on several other variables, were not
      included. No improvements were found in left ventricular size, stroke volume, and
      cardiac output after surgery in 4 of 5 studies, using radionuclides, 2
      dimensional echocardiography, radiographic planimetry, and cardiac output by the
      Fick method. Only a single study, with volumes calculated by squaring the
      diameter of the left ventricle from M-mode echocardiography, reported an increase
      (22%) in left ventricular stroke volume after operation, but that increased (17%)
      in the investigators' unoperated controls. This and 2 other studies used in this
      meta-analysis were also included in a meta-analysis conducted by Malek et al. In
      a fourth study, Malek et al included only the first study that found an
      improvement, but the final study reported no improvement. In conclusion, there is
      no reliable documentation of improved cardiac function from thoracic surgery for
      pectus excavatum.

PMID- 17560892
TI  - Superior vena cava syndrome induced by endocardial defibrillator and pacemaker
      leads.
AB  - Two cases of superior vena cava syndrome induced by endocardial defibrillator and
      pacemaker leads are described. The 2 patients had histories of multiple
      endocardial leads and device upgrades and venous thrombosis. The first patient
      was treated with laser lead extraction followed by percutaneous venoplasty and
      stenting. The second patient was treated conservatively with long-term
      anticoagulation. The 2 patients had symptomatic reduction. In conclusion,
      superior vena cava syndrome induced by transvenous leads is an uncommon but
      serious complication. Anticoagulation can be effective in select patients, but in
      severe cases, thrombolytic therapy or surgical or percutaneous intervention may
      be required.

PMID- 17560894
TI  - Predicting left ventricular end-diastolic pressure by echocardiography.

PMID- 17560895
TI  - Two-dimensional infrared correlation spectroscopy study of the interaction of
      oxidized and reduced cytochrome c with phospholipid model membranes.
AB  - We have used two-dimensional infrared correlation spectroscopy (2D-IR) to study
      the interaction and conformation of cytochrome c in the presence of a binary
      phospholipid mixture composed of a zwitterionic perdeuterated phospholipid and a
      negatively-charged one. The influence of the main temperature phase transition of
      the phospholipid model membranes on the conformation of cytochrome c has been
      evaluated by monitoring both the Amide I' band of the protein and the CH(2) and
      CD(2) stretching bands of the phospholipids. Synchronous 2D-IR analysis has been
      used to determine the different secondary structure components of cytochrome c
      which are involved in the specific interaction with the phospholipids, revealing
      the existence of a specific interaction between the protein with cardiolipin
      containing vesicles but not with phosphatidic acid-containing ones.
      Interestingly, 2D-IR is capable of showing the existence of significant changes
      in the protein conformation at the same time that the phospholipid transition
      occurs. In summary, 2D-IR revealed an important effect of the phospholipid phase
      transition of cardiolipin on the secondary structure of oxidized cytochrome c but
      not to either reduced cytochrome c or in the presence of phosphatidic acid,
      demonstrating the existence of specific intermolecular interactions between
      cardiolipin and cytochrome c.

PMID- 17560896
TI  - Leakage-free membrane fusion induced by the hydrolytic activity of PlcHR(2), a
      novel phospholipase C/sphingomyelinase from Pseudomonas aeruginosa.
AB  - PlcHR(2) is the paradigm member of a novel phospholipase C/phosphatase
      superfamily, with members in a variety of bacterial species. This paper describes
      the phospholipase C and sphingomyelinase activities of PlcHR(2) when the
      substrate is in the form of large unilamellar vesicles, and the subsequent
      effects of lipid hydrolysis on vesicle and bilayer stability, including vesicle
      fusion. PlcHR(2) cleaves phosphatidylcholine and sphingomyelin at equal rates,
      but is inactive on phospholipids that lack choline head groups. Calcium in the
      millimolar range does not modify in any significant way the hydrolytic activity
      of PlcHR(2) on choline-containing phospholipids. The catalytic activity of the
      enzyme induces vesicle fusion, as demonstrated by the concomitant observation of
      intervesicular total lipid mixing, inner monolayer-lipid mixing, and aqueous
      contents mixing. No release of vesicular contents is detected under these
      conditions. The presence of phosphatidylserine in the vesicle composition does
      not modify significantly PlcHR(2)-induced liposome aggregation, as long as Ca(2+)
      is present, but completely abolishes fusion, even in the presence of the cation.
      Each of the various enzyme-induced phenomena have their characteristic latency
      periods, that increase in the order lipid hydrolysis<vesicle aggregation<total
      lipid mixing<inner lipid mixing<contents mixing. Concomitant measurements of the
      threshold diacylglyceride+ceramide concentrations in the bilayer show that late
      events, e.g. lipid mixing, require a higher concentration of PlcHR(2) products
      than early ones, e.g. aggregation. When the above results are examined in the
      context of the membrane effects of other phospholipid phosphocholine hydrolases
      it can be concluded that aggregation is necessary, but not sufficient for
      membrane fusion to occur, that diacylglycerol is far more fusogenic than
      ceramide, and that vesicle membrane permeabilization occurs independently from
      vesicle fusion.

PMID- 17560897
TI  - Heterodimerization of y(+)LAT-1 and 4F2hc visualized by acceptor photobleaching
      FRET microscopy.
AB  - y(+)LAT-1 and 4F2hc are the subunits of a transporter complex for cationic amino
      acids, located mainly in the basolateral plasma membrane of epithelial cells in
      the small intestine and renal tubules. Mutations in y(+)LAT-1 impair the
      transport function of this complex and cause a selective aminoaciduria, lysinuric
      protein intolerance (LPI, OMIM #222700), associated with severe, complex clinical
      symptoms. The subunits of an active transporter co-localize in the plasma
      membrane, but the exact process of dimerization is unclear since direct evidence
      for the assembly of this transporter in intact human cells has not been
      available. In this study, we used fluorescence resonance energy transfer (FRET)
      microscopy to investigate the interactions of y(+)LAT-1 and 4F2hc in HEK293 cells
      expressing y(+)LAT-1 and 4F2hc fused with ECFP or EYFP. FRET was quantified by
      measuring fluorescence intensity changes in the donor fluorophore (ECFP) after
      the photobleaching of the acceptor (EYFP). Increased donor fluorescence could be
      detected throughout the cell, from the endoplasmic reticulum and Golgi complex to
      the plasma membrane. Therefore, our data prove the interaction of y(+)LAT-1 and
      4F2hc prior to the plasma membrane and thus provide evidence for 4F2hc
      functioning as a chaperone in assisting the transport of y(+)LAT-1 to the plasma
      membrane.

PMID- 17560898
TI  - Cholesterol modulation of membrane resistance to Triton X-100 explored by atomic
      force microscopy.
AB  - Biomembranes are not homogeneous, they present a lateral segregation of lipids
      and proteins which leads to the formation of detergent-resistant domains, also
      called "rafts". These rafts are particularly enriched in sphingolipids and
      cholesterol. Despite the huge body of literature on raft insolubility in non
      ionic detergents, the mechanisms governing their resistance at the nanometer
      scale still remain poorly documented. Herein, we report a real-time atomic force
      microscopy (AFM) study of model lipid bilayers exposed to Triton X-100 (TX-100)
      at different concentrations. Different kinds of supported bilayers were prepared
      with dioleoylphosphatidylcholine (DOPC), sphingomyelin (SM) and cholesterol
      (Chol). The DOPC/SM 1:1 (mol/mol) membrane served as the non-resistant control,
      and DOPC/SM/Chol 2:1:1 (mol/mol/mol) corresponded to the raft-mimicking
      composition. For all the lipid compositions tested, AFM imaging revealed that TX
      100 immediately solubilized the DOPC fluid phase leaving resistant patches of
      membrane. For the DOPC/SM bilayers, the remaining SM-enriched patches were slowly
      perforated leaving crumbled features reminiscent of the initial domains. For the
      raft model mixture, no holes appeared in the remaining SM/Chol patches and some
      erosion occurred. This work provides new, nanoscale information on the
      biomembranes' resistance to the TX-100-mediated solubilization, and especially
      about the influence of Chol.

PMID- 17560899
TI  - Forgive and remember revisited.

PMID- 17560900
TI  - Hemorrhage after pancreaticoduodenectomy: when is surgery still indicated?
AB  - BACKGROUND: This study analyzed presentation and management of hemorrhage after
      pancreaticoduodenectomy (PD) to determine the respective role of surgery and
      embolization. METHODS: From January 1992 to March 2005, 411 patients underwent PD
      and were analyzed with regard to postoperative hemorrhage. RESULTS: Hemorrhage
      occurred in 27 patients (7%), either within the first 3 postoperative days
      ("early" hemorrhage, n = 11) or after day 8 ("delayed" hemorrhage, n = 16,
      including 4 with "sentinel" bleeding). At the time of bleeding, 12 patients (44%)
      (all with delayed hemorrhage) had associated abdominal complications. Two
      patients had successful conservative treatment. Two stable patients with
      pseudoaneurysm, diagnosed by computed tomography scan, underwent successful
      embolization. Four patients with active bleeding underwent unsuccessful
      angiography. Overall, 23 patients were reoperated on without any completion
      pancreatectomy, 3 rebled, and 3 (11%) died (including 2 with delayed hemorrhage).
      CONCLUSIONS: Both embolization and surgery have a role in the management of
      hemorrhage after PD. For early hemorrhage, reoperation is appropriate. In case of
      sentinel bleeding, pseudoaneurysms can be detected by computed tomography scan
      and treated by embolization. For delayed active hemorrhage, reoperation is still
      indicated.

PMID- 17560901
TI  - Evidence-based management of hemorrhage after pancreaticoduodenectomy.

PMID- 17560902
TI  - Internal anal sphincterolysis for chronic anal fissure: a prospective, clinical,
      and manometric study.
AB  - BACKGROUND: The author proposes a technique of finger fragmentation of internal
      anal sphincter fibers to relieve anal sphincter spasm in patients with chronic
      anal fissures. This prospective study evaluates the clinical and functional
      outcome in a group of patients with chronic anal fissures. MATERIALS AND METHODS:
      Forty-five patients suffering from chronic anal fissure underwent the procedure
      termed "sphincterolysis." Anal manometry was performed prior to and at 6 and 24
      months after treatment. Anal incontinence was evaluated by means of a continence
      score. Patients were asked to rate the level of satisfaction at the last follow
      up. RESULTS: Forty-four patients completed the study. Symptom control was
      achieved in 7. 4 +/- 3 days in 91% patients whose fissures had healed when
      examined 4 weeks after the procedure. In 38 of these patients, pain was relieved
      at the time of first postoperative defecation. Recurrence of fissure was observed
      in 1 patient at the 6-month follow-up. Three patients had minor continence
      disturbances, which resolved within 6 months. Anal manometry before and after the
      procedure showed a significant reduction in mean resting pressure (MRP) (P <
      .001), while the maximum squeeze pressure before and after the treatment did not
      reach a statistically significant reduction. As regards satisfaction grading,
      79.5% of patients were highly satisfied with the procedure, while another 16% of
      patients rated the procedure as good. CONCLUSION: Internal anal sphincterolysis
      seems to be an effective, safe and easy procedure, which decreases anal resting
      pressure and achieves good symptom control with high patient satisfaction.

PMID- 17560903
TI  - Risk factors for intrahepatic recurrence after hepatectomy for hepatocellular
      carcinoma.
AB  - BACKGROUND: Long-term survival after hepatectomy for hepatocellular carcinoma is
      still poor because of tumor recurrence especially in the liver remnant. The risk
      factors for intrahepatic recurrence after liver resection are studied in our
      cohort of patients. METHODS: A retrospective analysis from a prospective database
      was performed on 76 consecutive successful hepatectomies for hepatocellular
      carcinoma. RESULTS: Twenty-two patients had intrahepatic recurrence. The
      following were not found to be risk factors for recurrence: age, sex, race,
      number of segments resected, and mean operating time. By using multivariate
      analysis, serum aspartate transaminase level, more than 1 hepatocellular
      carcinoma nodule, and presence of tumor thrombi were found to be significant risk
      factors. CONCLUSION: Patients who with these risk factors should undergo close
      follow-up to detect recurrence early; treatment with reresection,
      chemoembolization, or radiofrequency ablation can be considered.

PMID- 17560904
TI  - Bilateral thoracoscopic splanchnicectomy with sympathectomy for managing
      abdominal pain in cancer patients.
AB  - BACKGROUND: Simple interruption of splanchnic nerve can lead to incomplete
      transection of nerve fibers responsible for cancer-derived abdominal visceral
      because lots of neural communications exist. METHODS: From December 1999 to June
      2005, a total of 21 cancer patients underwent bilateral thoracoscopic segmental
      resection of splanchnic nerve with sympathectomy for intractable abdominal pain
      based on the anatomic observation of 26 embalmed Korean cadaveric specimens in
      Yonsei University Medical Center, Seoul, Korea. All patients were preoperatively
      asked to rate the extent of their current pain by using the numeric rating scale
      (NRS), where 0 indicated no pain and 10 indicated intractable pain. The
      effectiveness of this thoracoscopic procedure was assessed based on the NRS
      reevaluated after surgery. RESULTS: NRS score was significantly reduced after
      thoracoscopic surgery (1.71 +/- 1.10 versus 8.52 +/- 1.08, paired t test, P <
      .0001). Sixteen patients (76.2%) could tolerate pain without or with reduced dose
      of analgesics. No mortality and morbidity were found in this study. CONCLUSION:
      This bilateral thoracoscopic splanchnicectomy with sympathectomy is safe, easy,
      and effective method in managing cancer-derived visceral abdominal pain.

PMID- 17560905
TI  - Computed tomography severity index and C-reactive protein values predicting
      mortality in emergency and intensive care units for patients with severe acute
      pancreatitis.
AB  - BACKGROUND: Severe acute pancreatitis is a multisystem disease in which various
      local and systemic complications lead to high mortality. We retrospectively
      examined the clinical and biochemical factors that may influence the risk of
      mortality on admission to emergency and intensive care units (ICUs). METHODS:
      Sixty-eight patients were admitted into our hospital for acute pancreatitis and
      treated in our ICU for computed tomography-proven severe acute pancreatitis
      during the years 1997 to 2004. The clinical, biochemical, and radiologic data
      were reviewed from the computerized database, radiologic films, and patient
      records. RESULTS: The mortality rate during the ICU stay was 18% (12/68) and that
      during the whole period of hospitalization 26% (18/68). A C-reactive protein
      (CRP) value over 150 was the only independent predictor of mortality on admission
      into the emergency unit, whereas the computed tomography severity index and the
      elevated CRP value over 150 predicted significantly and independently mortality
      on admission into the ICU. Linear backward regression analysis showed that high
      CRP values and respiratory failure on ICU admission correlate with longer ICU
      stay. Men's ICU stays were longer than those of women. CONCLUSIONS: A high
      computed tomography severity index and CRP values over 150 on admission into the
      ICU are valuable predictors of the mortality risk. High CRP, renal and
      respiratory failure, and male gender are associated with longer ICU stay.

PMID- 17560906
TI  - Use of procalcitonin for early prediction of lethal outcome of postoperative
      sepsis.
AB  - BACKGROUND: To develop strategies for the prediction of sepsis outcome systemic
      procalcitonin (PCT) levels were correlated with various clinical parameters.
      METHODS: PCT levels and Acute Physiology and Chronic Health Evaluation (APACHE)
      II scores were assessed on the day of sepsis diagnosis in a large series (n =
      160) of patients developing sepsis after major visceral surgery. RESULTS: In
      multivariate analysis, systemic PCT and the APACHE II score could be identified
      as independent early predictive indicators of lethal sepsis. Combining both
      indicators at sepsis onset, a prognosis score could be calculated using binary
      logistic regression analysis allowing the identification of high- and low-risk
      groups. While 71% of the high-risk patients died of sepsis, 77% of patients
      assigned to the low-risk group survived the septic complication (sensitivity 71%,
      specificity 77%). CONCLUSION: Calculation of the prognosis-score allowed for an
      early prediction of the septic course with high sensitivity and specificity. This
      information could aid in deciding on adequate treatment strategies.

PMID- 17560907
TI  - Long-term outcome, colonic motility, and sphincter performance after Swenson's
      procedure for Hirschsprung's disease: a single-center 2-decade experience with
      346 cases.
AB  - BACKGROUND: The aim of this study is to explore the long-term outcome and the
      colon and sphincter function in children undergoing the Swenson's operation for
      Hirschsprung's disease (HD). METHODS: Three hundred forty-six children (266 males
      and 80 females) undergoing Swenson's operation for HD for 8 to 20 years were
      followed up. Barium enema and defecography, total and segmental colonic transit
      time with the simplified radioopaque markers, and the anorectal vector manometry
      were used. RESULTS: Stooling patterns were fair in most patients, and the
      functional examinations were abnormal in few cases. CONCLUSIONS: The long-term
      outcome is satisfactory in most of the children undergoing the Swenson's
      operation for HD, but it is still not as good as what the surgeons have expected.
      This is probably because of the abnormal colonic motility and/or the dysfunctions
      of the internal anal sphincter.

PMID- 17560908
TI  - Assessment of comorbid conditions in veteran patients after Roux-en-Y gastric
      bypass.
AB  - BACKGROUND: The present study assessed the degree to which comorbid conditions
      improved after bariatric surgery in veteran patients. METHODS: A retrospective
      review of 55 patients (age 49.1 +/- 1.2, body mass index 49.3 +/- 1.2 kg/m2; 62%
      male) who underwent open Roux-en-Y gastric bypass surgery at the Dallas Veterans
      Administration Medical Center was performed. Univariate and multivariate analyses
      were used to determine factors associated with outcomes. RESULTS: There were 17
      minor (8 patients with anastomotic ulcer, 5 patients with hernia, 1 patients with
      cholecystitis, 1 patients with a wound infection, and 2 patients with seroma) and
      4 major (3 patients with pulmonary embolism and 1 patients with gastrojejunostomy
      leak) complications. Univariate analysis demonstrated that body mass index was
      associated with increased length of hospital stay but not with morbidity. Age was
      not associated with length of hospital stay or morbidity. There was improvement
      in 91% of patients affected with diabetes mellitus, in 89% with hypertension, in
      80% with dyslipidemia, and in 62% with obstructive sleep apnea. COMMENTS: Roux-en
      Y gastric bypass results in a marked amelioration or elimination of obesity
      related comorbid conditions in veteran patients. Morbidity and mortality are
      within acceptable rage for these patients with substantial comorbidities.

PMID- 17560909
TI  - Mediastinal hyperfunctioning parathyroids: incidence, evolving treatment, and
      outcome.
AB  - BACKGROUND: The evaluation and treatment of hyperfunctioning mediastinal
      parathyroid gland(s) (MPG) is evolving. This study reports our overall experience
      with MPG in a tertiary referral center. METHODS: A prospective database of 922
      patients undergoing parathyroidectomy by 2 surgeons from 1982 to 2005 was
      reviewed. RESULTS: Thirty-two of 922 (3.5%) patients had MPG. Nine (28%) patients
      had a prior failed parathyroidectomy. Sestamibi and computed tomography scans
      were correctly positive in 24/28 (86%) and 6/7 (86%) patients, respectively. MPGs
      were removed via cervical approach in 22 (69%). Eleven of 22 patients had a
      focused cervical approach. Nine MPGs required a limited sternotomy (n = 3) or a
      successful radioguided video-assisted thoracoscopic approach (VATS, n = 4) for
      removal. Two VATS were converted to a full sternotomy. One patient refused
      surgery. All patients who required sternotomy/VATS had MPGs caudal to the
      innominate vein. Twenty-nine of 31 (94%) patients were cured. Two are stable on
      calcimimetics. One patient has permanent hypoparathyroidism. CONCLUSIONS: Most
      MPGs can be removed through a cervical approach. Preoperative Sestamibi and
      computed tomography scans can help the surgeon plan the best initial surgical
      approach. Those below the innominate vein require a thoracic procedure,
      preferably a radioguided probe-assisted thoracoscopic resection with
      intraoperative parathyroid hormone (ioPTH). An alternative to surgical removal is
      medical treatment.

PMID- 17560910
TI  - Explaining insurance-related and racial disparities in the surgical management of
      patients with acute appendicitis.
AB  - BACKGROUND: Race and insurance status influence the likelihood of undergoing
      laparoscopic appendectomy (LA) versus open appendectomy for the treatment of
      acute appendicitis. We hypothesized that these disparities are caused by
      presenting hospitals' use of LA. METHODS: The analysis included 26,104
      appendectomies for acute appendicitis in New York State during 2003 and 2004.
      Multiple logistic regression was used to determine independent predictors for
      undergoing LA versus open appendectomy. RESULTS: Before adjustment for individual
      hospital use of LA, both white patients (odds ratio [OR] = 1.28, 95% confidence
      interval [CI] 1.21-1.36; P < .0001] and privately insured patients (OR = 1.52,
      95% CI 1.44-1.61; P < .0001) were more likely to undergo LA. Controlling for
      differential hospitals' use of LA decreased the OR for laparoscopic surgery to
      1.08 (95% CI 1.01-1.15; P = .04) for white patients and to 1.22 (95% CI 1.15
      1.31; P < .0001) for privately insured patients. CONCLUSIONS: Differences in
      presenting hospitals' use of LA maintain racial and, to a lesser extent,
      insurance-related disparities in the surgical management of patients with acute
      appendicitis.

PMID- 17560911
TI  - Treatment and prognosis of gastric stump carcinoma in comparison with primary
      proximal gastric cancer.
AB  - BACKGROUND: The intention of this study was to evaluate the outcome of patients
      with gastric stump cancer (GSC) in comparison with patients treated for primary
      proximal gastric cancer (PPGC). METHODS: Nineteen patients with GSC undergoing
      surgery between January 1989 and August 2005 were compared with 194 PPGC patients
      treated during the same time period. Various factors such as epidemiologic data,
      type of treatment, and histopathologic data were evaluated in the analysis.
      RESULTS: The overall 5-year disease-specific survival was 42% for resected GSC
      patients in comparison with 37% for resected PPGC patients. There was no
      statistically significant difference in the survival rate detected between these
      2 groups. On multivariate analysis the infiltration of the gastrojejunal
      anastomosis by the carcinoma was shown to be a significant predictor for the
      outcome of patients with GSC. CONCLUSIONS: In summary, no significant difference
      in the outcome between GSC and PPGC has been detected.

PMID- 17560912
TI  - Partially absorbable meshes for hernia repair offer advantages over nonabsorbable
      meshes.
AB  - BACKGROUND: The aim of this study was to establish whether new prosthetic
      materials with absorbable components, designed to reduce the amount of foreign
      material in abdominal wall repair, offer advantages over the conventional
      polypropylene meshes. METHODS: Seven x 5 cm defects created in the anterior
      abdominal wall of New Zealand white rabbits were repaired by using a
      nonabsorbable polypropylene prosthesis (Surgipro; Tyco, Barcelona, Spain) or 1 of
      2 partially absorbable prostheses available on the market (Vypro II and Ultrapro;
      Johnson & Johnson, St. Stevens-Woluwe, Belgium). At 14 and 90 days after surgery,
      tissue/prosthesis specimens were subjected to histological studies, biomechanical
      strength tests, and shrinkage evaluation. RESULTS: At 90 days, the absorbable
      filaments of Vypro II had been completely reabsorbed, whereas Ultrapro only
      showed signs of biodegradation in a few zones. Host tissue infiltration and
      collagen I deposition in the 3 reticular meshes was optimal. Macrophage counts,
      mesh shrinkage, and biomechanical resistance values were similar. CONCLUSIONS:
      Partially absorbable prostheses perform as well as the standard polypropylene
      mesh and have the benefit that less foreign material remains in the recipient,
      without compromising mechanical resistance.

PMID- 17560913
TI  - Intrapancreatic splenunculus.
AB  - Intrapancreatic accessory spleens are uncommon, however, the recognition and
      appropriate confirmatory diagnostic imaging of an intrapancreatic splenunculus is
      important to avoid an unnecessary surgery for a suspected pancreatic tumor. We
      present a patient who underwent a distal pancreatectomy for a suspected
      pancreatic neuroendocrine tumor based on clinical history, radiologic imaging,
      and a positive labeled octreotide scan. A brief review of intrapancreatic
      splenunculi and confirmatory diagnostic imaging is discussed.

PMID- 17560914
TI  - Spontaneous rupture of adrenocortical carcinoma.
AB  - Massive hemorrhage from an adrenocortical carcinoma seldom occurs in the
      retroperitoneal or abdominal cavity. We report a case of spontaneous rupture of
      primary adrenocortical carcinoma occurring in an adolescent. A right
      adrenalectomy with complete removal of the tumor was performed successfully.

PMID- 17560915
TI  - A primer on transarterial, chemical, and thermal ablative therapies for hepatic
      tumors.
AB  - BACKGROUND: Surgical resection is the only potentially curative approach for
      patients with primary and metastatic liver tumors. Unfortunately, most patients
      with hepatic malignancy are precluded from resection due to multifocal disease,
      anatomic limitations, inadequate functional liver reserve, extrahepatic
      metastases, or medical comorbidities. Consequently, several methods of tumor
      ablation have been developed as alternate treatment strategies for patients with
      unresectable hepatic tumors or as adjuncts in total cancer therapy. The purpose
      of this review is to inclusively define the various ablation modalities available
      (transarterial, chemical, and thermal ablative), and to describe the procedures,
      general applications, and reported outcomes. DATA SOURCES: A MEDLINE and CINAHL
      search of the English-language literature was performed on transarterial,
      chemical, and thermal ablative therapies. CONCLUSIONS: Presently, radiofrequency
      thermal ablation is the most widely applicable liver-directed modality for
      hepatic tumor ablation, enabling treatment of primary and metastatic tumors.
      However, other transarterial and thermoablative techniques are available with
      accumulating data for their use. Lacking at present are studies that define the
      role and potential benefit of the various liver-directed modalities in the
      treatment algorithm for hepatic tumors.

PMID- 17560916
TI  - Preliminary evaluation of the Web Initiative for Surgical Education (WISE-MD).
AB  - BACKGROUND: Major changes in health care delivery and financing have negatively
      impacted students' experience during the surgery clerkship, particularly their
      exposure to physicians' decision-making processes and to the continuity of
      patient care. In response to these dilemmas in surgical education, we have
      developed the Web Initiative for Surgical Education (WISE-MD), a comprehensive
      surgery clerkship curriculum delivered through multimedia teaching modules and
      designed to enhance exposure to surgical disease and clinical reasoning. METHODS:
      As part of the process of creating WISE-MD, we conducted preliminary studies to
      assess the impact of this computer-assisted approach on students' knowledge,
      clinical reasoning, and satisfaction. RESULTS: Compared to students who did not
      view the modules, early data show a trend toward improved knowledge and an
      improvement in clinical reasoning for students who used the WISE-MD modules. This
      effect was specific to the clinical content area addressed in the module seen by
      the students. Most students felt the module was superior to traditional teaching
      methods and enhanced their understanding of surgical technique and anatomy.
      CONCLUSIONS: WISE-MD, a theory-driven example of a concerted technology-based
      approach to surgical education, has the potential to address the myriad problems
      of today's clinical learning environment.

PMID- 17560917
TI  - Wrapping of skeletonized and divided vessels using the falciform ligament in
      distal pancreatectomy.
AB  - BACKGROUND: A pancreatic fistula is a major cause of morbidity in patients
      undergoing distal pancreatectomy (DP). A pancreatic fistula may expose
      skeletonized or divided vessels directly to pancreatic juice, creating a setting
      for vessel erosion and delayed intra-abdominal hemorrhage (DIH). With the aim of
      protecting vessels near the pancreatic stump from potential pancreatic fistulas,
      we have adopted a surgical option by which these vessels are wrapped using a
      pedicled falciform ligament. METHODS: After completing DP, the pedicled falciform
      ligament is spread out widely on major vessels exposed during resection near the
      pancreatic stump, and fixed to the surrounding retroperitoneal connective tissue.
      These procedures allow the complete separation of these vessels from the
      pancreatic stump. We reviewed the cases of 8 patients who underwent DP including
      these procedures. RESULTS: The mobilization of the falciform ligament and the
      wrapping of the vessels were successfully performed without any complications.
      Although 2 patients (14.5%) developed pancreatic fistulas, DIH did not occur in
      any of the patients. CONCLUSIONS: The wrapping of the skeletonized and divided
      vessels using a pedicled falciform ligament is simple and easy, and may be an
      effective prophylactic measure against DIH following DP.

PMID- 17560918
TI  - Open anterior approaches for lumbar spine procedures.
AB  - With the advent of anterior lumbar interbody fusion (ALIF) and artificial discs
      as common procedures for the treatment many spinal problems such as
      pseudoarthrosis, degenerative disc disease and internal disc disruption from
      trauma, anterior exposure has become an increasingly popular procedure for the
      general, thoracic, urologic and vascular surgeon. Despite this, the body of
      literature describing this procedure is lacking. Dividing the approach for
      anterior spinal surgery into the thoracolumbar, mid-lumbar, and lumbosacral
      regions, we describe the basic techniques and anatomy needed to perform these
      open approaches, specifically, repairs of disc spaces T12-L2, L2-5, and L5-S1,
      respectively. The technique for the retroperitoneal approach will be discussed in
      detail; however, issues involved with indications for transperitoneal approach
      and technical "pearls" will also be discussed.

PMID- 17560919
TI  - A management algorithm for esophageal perforation.
AB  - Despite the prolonged morbidity caused by a major surgery and the high occurrence
      of continued leakage, primary repair has been the standard treatment for
      esophageal perforations. We believe that management using removable esophageal
      stents is both simpler and more effective. Over the past 3 years, we have treated
      14 patients using esophageal stents, and the procedure was successful in all
      patients. Because of the shorter bed rest that follows endoscopic Polyflex stent
      (Rush, Inc; Teleflex Medical, Duluth, GA) placement, it is very likely that the
      care of patients with esophageal perforation will be changed over time.

PMID- 17560920
TI  - Tape-guided living donor left hepatectomy.
AB  - A procedure of tape-guided living donor left hepatectomy is described. A tape was
      placed along the anterior wall of the inferior vena cava for left liver with
      caudate lobe, and along Arantius' ligament for left liver without caudate lobe.
      The final step of liver transection was applied by dividing the liver parenchyma
      under tape guidance. This procedure contributed to safe and accurate anatomic
      procurement of left liver grafts in living donor hepatectomy.

PMID- 17560921
TI  - Postoperative video debriefing reduces technical errors in laparoscopic surgery.
AB  - BACKGROUND: Because of the learning curve required to master laparoscopic
      procedures, there is a growing concern that patient safety may be compromised due
      to technical errors by a novice surgeon. We evaluated the effect of videotape
      debriefing on the performance of a complex laparoscopic procedure. METHODS:
      Twenty-four surgical residents performed a laparoscopic jejunojejunal anastomosis
      under the supervision of a single laparoscopic surgeon. All procedures were
      videotaped. Half of the residents underwent video debriefing. Videotapes were
      analyzed for knot-tying time, anastomotic time, and frequency of minor technical
      errors and adverse events. The performance of the debriefed group was compared
      with a non-debriefed group. RESULTS: Knot-tying time, minor errors, and
      anastomotic time were similar between the debriefed and non-debriefed groups.
      However, adverse events from technical errors were more frequent in the non
      debriefed group (chi2 = 7.647, P = .006). CONCLUSIONS: Postoperative video
      debriefing is an effective educational tool for reducing adverse events during a
      complex laparoscopic procedure.

PMID- 17560922
TI  - Comparison of learning curves and skill transfer between classical and robotic
      laparoscopy according to the viewing conditions: implications for training.
AB  - BACKGROUND: The purpose of this study was to evaluate the perceptual (2
      dimensional [2D] vs. 3-dimensional [3D] view) and instrumental (classical vs.
      robotic) impacts of new robotic system on learning curves. METHODS: Forty medical
      students without any surgical experience were randomized into 4 groups (classical
      laparoscopy with 3D-direct view or with 2D-indirect view, robotic system in 3D or
      in 2D) and repeated a laparoscopic task 6 times. After these 6 repetitions, they
      performed 2 trials with the same technique but in the other viewing condition
      (perceptive switch). Finally, subjects performed the last 3 trials with the
      technique they never used (technical switch). Subjects evaluated their
      performance answering a questionnaire (impressions of mastery, familiarity,
      satisfaction, self-confidence, and difficulty). RESULTS: Our study showed better
      performance and improvement in 3D view than in 2D view whatever the instrumental
      aspect. Participants reported less mastery, familiarity, and self-confidence and
      more difficulty in classical laparoscopy with 2D-indirect view than in the other
      conditions. CONCLUSIONS: Robotic surgery improves surgical performance and
      learning, particularly by 3D view advantage. However, perceptive and technical
      switches emphasize the need to adapt and pursue training also with traditional
      technology to prevent risks in conversion procedure.

PMID- 17560923
TI  - Effects of retrograde gastric electrical stimulation with pulse trains on gastric
      emptying of solids and plasma hormones in dogs.
AB  - BACKGROUND: Retrograde gastric electrical stimulation (RGES) is proposed as a
      novel therapy for obesity. However, mechanisms of RGES are not fully
      investigated. The aim of this study was to investigate the effects of RGES with
      trains of pulses on gastric slow waves, gastric emptying of solids, and plasma
      concentrations of satiety-related peptides and glucose. METHODS: Seven female
      beagle dogs implanted with 4 pairs of gastric electrodes on the gastric serosa
      were studied (control and RGES). Gastric emptying, gastric slow waves, and signs
      were recorded in each session. Plasma leptin, insulin, glucagons, and glucose
      were also measured. RESULTS: RGES with pulse trains (a pulse width of 2
      milliseconds) significantly decreased gastric emptying of solids and plasma
      insulin but has no effect on plasma leptin, glucagons, and glucose. CONCLUSION:
      Acute gastric electrical stimulation with pulse trains is able to decrease
      gastric emptying of solids and plasma insulin but has no effects on plasma
      leptin, glucagons, and glucose.

PMID- 17560924
TI  - T-cell cytokines affect mucosal immunoglobulin A transport.
AB  - BACKGROUND: Secretory immunoglobulin A (sIgA) is the principle immune defense
      against bacteria and other pathogens in the gut and other mucosal surfaces. sIgA
      is produced locally by plasma cells and transported (transcytosis) across
      epithelial cells into luminal secretions. sIgA production and transcytosis are
      governed by multiple signals, which may be affected by T cells. The purpose of
      this study was to elucidate the role of the Th1-type cytokine, interferon gamma
      (IFN-gamma), and the Th2-type cytokine interleukin-4 (IL-4) on IgA transcytosis
      across intestinal epithelial cells in vitro. METHODS: HT-29 cell monolayers were
      established in a 2-chamber cell culture system. Cell monolayers were exposed to
      either IFN-gamma, IL-4, or both on the apical or basal side of the culture system
      systems for 48 hours. Dimeric IgA then was added to the basolateral chamber and
      transcytosis into the apical chamber was quantified by enzyme-linked
      immunosorbent assay at timed intervals. IgA transcytosis across HT-29 cells
      without prior addition of either cytokine served as a control. RESULTS: Poly Ig
      receptor up-regulation was shown by both IFN and IL-4. A combination of these 2
      cytokines caused the greatest increase in receptor expression. A total of 3.7% of
      HT-29 cells expressed the polymeric Ig receptor in the control group. This
      increased to 23.7% in IL-4-treated cells, 66.3% in IFN-gamma-treated cells, and
      71.5% of cells treated with both cytokines. These findings re-show previously
      published findings. The effects of IFN-gamma added to the basal chamber of HT-29
      cell cultures shows a 7- to 10-fold increase in sIgA transcytosis at the 1-, 3-,
      and 12-hour time intervals. The effect of the addition of IL-4 to the basal
      chamber was similar to the results noted with IFN-gamma alone. The greatest IgA
      transcytosis was noted when IFN-gamma and IL-4 both were added to the basal
      chamber. However, these same results did not occur with cytokine exposure to the
      apical side of cell monolayers. CONCLUSIONS: IFN-gamma and IL-4 increased IgA
      transport across HT-29 cells in a polar fashion. An increased effect on IgA
      transport was noted with the combination of IFN-gamma and IL-4. Delivery of T
      cell cytokines to mucosal surfaces may support local antibody defense of mucosal
      surfaces and prevent infection.

PMID- 17560925
TI  - Basic science career development.

PMID- 17560926
TI  - Sentinel nodes might not reflect nodal status after neoadjuvant chemotherapy.

PMID- 17560927
TI  - Good science requires sound biostatistical principles.

PMID- 17560929
TI  - A multicenter trial of sentinel lymph node mapping in colorectal cancer:
      prognostic implications for nodal staging and recurrence.

PMID- 17560930
TI  - Regarding "Basic science career development".

PMID- 17560931
TI  - Sentinel node mapping in colorectal cancer.

PMID- 17560932
TI  - Venous bleeding from traction of transverse mesocolon.

PMID- 17560933
TI  - Management of splenic pseudocyst.

PMID- 17560934
TI  - Laparoscopy as an educational and recruiting tool.

PMID- 17560935
TI  - Erythropoietin induces heme oxygenase-1 expression and attenuates oxidative
      stress.
AB  - Recent studies have established that erythropoietin (EPO) is a pleiotropic
      cytokine. In this study we investigated whether pleiotropic effects of EPO may
      involve regulation of heme oxygenase (HO)-1, an anti-oxidative stress protein. A
      stimulatory effect of EPO on HO-1 expression was demonstrated in cultured renal
      endothelial cells, in which EPO decreased intracellular oxidative stress and
      provided cytoprotection against H(2)O(2). These beneficial effects were partially
      reversed by a HO-1 inhibitor. We then evaluated whether EPO induces HO-1 and
      ameliorates renal injury in vivo. Administration of EPO to Dahl salt-sensitive
      (DS) rats with low salt diet, a model of chronic tubulointerstitial injury,
      reduced proteinuria, and renal injury including peritubular capillaries
      rarefaction as compared to vehicle-treated DS rats. This renoprotection was
      associated with up-regulation of HO-1 in the kidney. In conclusion, EPO-induced
      HO-1 expression is likely to provide cytoprotection against oxidative stress.

PMID- 17560936
TI  - Expression of transient receptor potential vanilloid 1 (TRPV1) in synovial
      fibroblasts from patients with osteoarthritis and rheumatoid arthritis.
AB  - The transient receptor potential vanilloid 1 (TRPV1) is a nonselective cation
      channel, which is mainly expressed by nociceptive neurons in dorsal root and
      trigeminal ganglia. However, there is increasing evidence that TRPV1 expression
      is not limited to primary afferent neurons but that the receptor is expressed in
      various cell types throughout the body. Here, we demonstrate the expression of
      TRPV1 in synovial fibroblasts (SF) from patients with symptomatic osteoarthritis
      (OA) and rheumatoid arthritis (RA). In addition, the mRNA expression of TRPV1 was
      shown in PBMCs from healthy controls and from OA patients. The presence of TRPV1
      was confirmed at the protein level. Stimulation of cultured OA- and RA-SF with
      the TRPV1 agonist capsaicin led to increased expression of IL-6 mRNA as well as
      of IL-6 protein in the cell culture supernatants. IL-6 protein expression could
      be antagonized with capsazepine. Thus, we hypothesize that TRPV1 may play a role
      in non-neuronal mechanisms that might modulate nociception in symptomatic OA and
      RA patients.

PMID- 17560937
TI  - (-)-Epicatechin elevates nitric oxide in endothelial cells via inhibition of
      NADPH oxidase.
AB  - Dietary (-)-epicatechin is known to improve bioactivity of (*)NO in arterial
      endothelium of humans, but the mode of action is unclear. We used the fluorophore
      4,5-diaminofluorescein diacetate to visualize the (*)NO level in living human
      umbilical vein endothelial cells (HUVEC). Untreated cells showed only a weak
      signal, whereas pretreatment with (-)-epicatechin (10 microM) or apocynin (100
      microM) elevated the (*)NO level. The effects were more pronounced when the cells
      were treated with angiotensin II with or without preloading of the cells with
      (*)NO via PAPA-NONOate. While (-)-epicatechin scavenged O2(*-), its O-methylated
      metabolites prevented O2(*-) generation through inhibition of endothelial NADPH
      oxidase activity, even more strongly than apocynin. From the effect of 3,5
      dinitrocatechol, an inhibitor of catechol-O-methyltransferase (COMT), on HUVEC it
      is concluded that (-)-epicatechin serves as 'prodrug' for conversion to apocynin
      like NADPH oxidase inhibitors. These data indicate an (*)NO-preserving effect of
      (-)-epicatechin via suppression of O2(*-)-mediated loss of (*)NO.

PMID- 17560938
TI  - WITHDRAWN: Solvent effect on PCR from a viewpoint of a change of microscopic
      environment of Mg(2+) in a solution.
AB  - This article has been withdrawn at the request of the editor. The Publisher
      apologizes for any inconvenience this may cause. The full Elsevier Policy on
      Article Withdrawal can be found at
      http://www.elsevier.com/locate/withdrawalpolicy.

PMID- 17560939
TI  - Correlation of Golgi localization of ZW10 and centrosomal accumulation of
      dynactin.
AB  - ZW10 participates in the termination of the spindle checkpoint during mitosis by
      interacting with dynamitin, a subunit of the dynein accessory complex dynactin.
      We previously showed that ZW10 is attached to the endoplasmic reticulum through
      RINT-1 in interphase HeLa cells and involved in membrane transport between the
      endoplasmic reticulum and Golgi. Although a recent study demonstrated that ZW10
      is localized in the Golgi in COS7 cells, the mechanism that regulates ZW10
      localization remains unknown. In this study we showed a correlation between the
      Golgi localization of ZW10 and the centrosomal accumulation of dynactin. The
      amounts of ZW10 associated with dynactin were larger in cells where ZW10 was
      present in the Golgi than those where ZW10 was not in the Golgi. The targeting of
      ZW10 to the perinuclear Golgi region was found to depend on the perinuclear
      accumulation of dynactin, suggesting that dynactin regulates ZW10 localization.

PMID- 17560940
TI  - Regulation of c-myc through intranuclear localization of its RNA subspecies.
AB  - We used fluorescence in situ hybridization (FISH) to detect c-myc RNA subspecies
      in human COLO 320DM tumor cells. Although the FISH procedure removed the majority
      of RNAs from the nucleolus, c-myc RNA continued to be detected in both the
      nucleoplasm and nucleolus. This finding suggests stable association between c-myc
      RNA and the nucleolus. Nucleolar accumulation of c-myc RNA appeared to be
      temporally regulated by cell-cycle progression. Hybridization with exon- and
      strand-specific RNA probes indicated that the non-protein coding exon 1 plays a
      novel role in determining the subnuclear localization of c-myc RNA. Antisense RNA
      targeting exon 2 localized only with nucleoplasmic foci, where it might interact
      with the sense strand. Thus, c-myc gene expression may be regulated by
      intranuclear localization of its RNA.

PMID- 17560941
TI  - Stable activity of a deubiquitylating enzyme (Usp2-cc) in the presence of high
      concentrations of urea and its application to purify aggregation-prone peptides.
AB  - Chemical synthesis of long or aggregation-prone peptide has been problematic. Its
      biological production has an advantage in that point, but it often forms
      inclusion body which creates difficulties in recovery of targets. As a
      deubiquitylating enzyme (Usp2-cc) was shown in this study to maintain its
      activity even in the presence of up to 4M urea, target peptide was purified by a
      single step of chromatography after overexpression as inclusion body,
      solubilization in urea and cleavage by the enzyme from the fusion protein
      consisting of GroES (used for high expression and easy to handle), ubiquitin (as
      a cleavage site) and target peptide. This system is a convenient tool for
      production of peptides that are difficult to be chemically synthesized and
      biologically purified.

PMID- 17560942
TI  - XBP-1, a key regulator of unfolded protein response, activates transcription of
      IGF1 and Akt phosphorylation in zebrafish embryonic cell line.
AB  - The unfolded protein response (UPR) is a conserved and adaptive cellular response
      to increase cell survival during ER stress. XBP-1 spliced form (XBP-1S) generated
      by IRE1 endoribonuclease is a key transcriptional regulator in UPR to activate
      genes involved in protein folding and degradation to restore ER function.
      Although Akt activation was suggested to be a pro-survival pathway activated
      during ER stress, the signal to trigger Akt is still not clear. In this study, we
      report IGF1 transcription and Akt phosphorylation are enhanced in XBP-1S stably
      overexpressed clone of zebrafish embryonic cell line (ZF4). In addition,
      zebrafish IGF1 intron1 with predicted UPRE (XBP-1S binding sites) and ERSE
      (ATF6/XBP-1S binding site) linked with basal promoter could be activated by XBP
      1S, not by XBP-1 unspliced form (XBP-1U). Furthermore, we demonstrate that
      expression of endogenous IGF1 is transiently induced as XBP-1 splicing during ER
      stress in parallel to ER chaperone GRP78/Hspa5 and ER resided E3 ubiquitin ligase
      Synoviolin in ZF4 cells by quantitative PCR. Our results suggest zebrafish XBP-1S
      not only activates genes responsible for protein folding, transporting,
      glycosylation and ER associated degradation but also activates anti-apoptosis
      signal via IGF1/Akt pathway in unfolded protein response to cope with ER stress.

PMID- 17560943
TI  - An outwardly rectifying anionic background current in atrial myocytes from the
      human heart.
AB  - This report describes a hitherto unreported anionic background current from human
      atrial cardiomyocytes. Under whole-cell patch-clamp with anion-selective
      conditions, an outwardly rectifying anion current (I(ANION)) was observed, which
      was larger with iodide than nitrate, and with nitrate than chloride as charge
      carrier. In contrast with a previously identified background anionic current from
      small mammal cardiomyocytes, I(ANION) was not augmented by the pyrethroid
      tefluthrin (10 microM); neither was it inhibited by hyperosmolar external
      solution nor by DIDS (200 microM); thus I(ANION) was not due to basal activity of
      volume-sensitive anion channels. I(ANION) was partially inhibited by the Cl(-)
      channel blockers NPPB (50 microM) and Gly H-101 (30 microM). Incorporation of
      I(ANION) into a human atrial action potential (AP) simulation led to depression
      of the AP plateau, accompanied by alterations to plateau inward calcium current,
      and to AP shortening at 50% but not 90% of complete repolarization, demonstrating
      that I(ANION) can influence the human atrial AP profile.

PMID- 17560944
TI  - Role of cyclooxygenase-2 in tetrahydrobiopterin-induced dopamine oxidation.
AB  - Dopamine is considered one of the main contributing factors in the induction of
      oxidative stress and selective dopaminergic neurodegeneration in Parkinson's
      disease. We have previously reported that tetrahydrobiopterin (BH4) leads to
      dopamine oxidation and renders dopamine-producing cells vulnerable. In the
      present study, we found that BH4 selectively upregulates cyclooxygenase-2 (COX-2)
      expression in dopaminergic cells. BH4 caused an induction of COX-2 mRNA, and a
      critical regulatory motif for BH4-induced transcriptional activation of COX-2 is
      CRE/AP-1. COX-2 can oxidize dopamine and cause oxidative stress, which is
      evidenced by the findings that significant increase in dopamine-chrome formation
      and protein carbonyl contents by BH4-induced COX-2 up-regulation, and the
      increases are abolished by COX-2 selective inhibitor meloxicam. Increased COX-2
      promotes dopaminergic neurodegeneration in both SH-SY5Y cells and rat
      mesencephalic neurons. These data suggest that BH4-induced COX-2 expression is
      responsible for dopamine oxidation, leading to the preferential vulnerability of
      dopaminergic cells in Parkinson's disease.

PMID- 17560945
TI  - Identification of the suppressive factors for human immunodeficiency virus type-1
      replication using the siRNA mini-library directed against host cellular genes.
AB  - We performed the screening to find the novel host factors affecting human
      immunodeficiency virus type-1 (HIV-1) replication using the siRNA mini-library
      consisted with 257 siRNAs directed against cellular genes. J111 cells, a human
      acute monocytic leukemia cell line, were transfected with individual siRNA,
      followed by either infected or transfected with the HIV-1 molecular clone with
      luciferase reporter gene in 96-well plate format. The results showed that six
      siRNAs significantly enhanced the HIV-1 replication in J111 cells, indicating
      that the target cellular genes of those siRNAs may negatively regulate HIV-1
      replication in normal cell culture condition. We also discuss the possible
      mechanisms by which those cellular proteins regulate viral replication.

PMID- 17560946
TI  - Differential endoplasmic reticulum stress signaling pathways mediated by iNOS.
AB  - Accumulated misfolded proteins in endoplasmic reticulum (ER) activate ER stress
      signaling pathways. Here we identified the ER factors that generate ROS
      molecules. After mouse NIH3T3 cells were treated with either tunicamycin or
      thapsigargin, oxidative stress was induced. We found inducible nitric oxide
      synthase (iNOS) was involved in the generation of ROS induced by ER stress. When
      thapsigargin-treated cells were pre-treated with iNOS inhibitors 1400W or L
      canavanine, their ER stress-induced oxidative stress was almost totally
      abolished. This effect was not seen in the cells treated with tunicamycin.
      Therefore, iNOS appears to mediate the ER stress subpathway caused by Ca(2+)
      efflux. To the contrary, after we treated the cells with the 26S proteasome
      inhibitors lactacystin or MG-132, the UPR-induced oxidative stress dramatically
      increased, indicating that clearing misfolded proteins from the ER lumen reduced
      the oxidative stress. Therefore, the oxidative stress induced by ER stress
      signaling is mediated through both iNOS-dependent and -independent subpathways.

PMID- 17560947
TI  - Generation of 'humanized' hCYP1A1_1A2_Cyp1a1/1a2(-/-) mouse line.
AB  - Human/rodent CYP1A1 and CYP1A2 orthologs are well known to exhibit species
      specific differences in substrate preferences and rates of metabolism. This lab
      previously characterized a BAC-transgenic mouse carrying the human CYP1A1_CYP1A2
      locus; in this line, human dioxin-inducible CYP1A1 and basal vs dioxin-inducible
      CYP1A2 have been shown to be expressed normally (with regard to mRNAs, proteins
      and three enzyme activities) in every one of nine mouse tissues studied. The
      mouse Cyp1a1 and Cyp1a2 genes are oriented head-to-head and share a bidirectional
      promoter region of 13,954 bp. Using Cre recombinase and loxP sites inserted 3' of
      the stop codons of both genes, we show here a successful interchromosomal
      excision of 26,173 bp that ablated both genes on the same allele. The Cyp1a1/1a2(
      ) double-knockout allele was bred with the "humanized" line; the final product is
      the hCYP1A1_1A2_Cyp1a1/1a2(-/-) line on a theoretically >99.8% C57BL/6J genetic
      background-having both human genes replacing the mouse orthologs. This line will
      be valuable for human risk assessment studies involving any environmental
      toxicant or drug that is a substrate for CYP1A1 or CYP1A2.

PMID- 17560948
TI  - Apical P2XR contribute to [Ca2+]i signaling and Isc in mouse renal MCD.
AB  - We examined P2X receptor expression and distribution in the mouse collecting duct
      (CD) and their functional role in Ca(2+) signaling. Both P2X(1) and P2X(4) were
      detected by RT-PCR and Western blot. Immunohistochemistry demonstrated apical
      P2X(1) and P2X(4) immunoreactivity in principal cells in the outer medullary CD
      (OMCD) and inner medullary CD (IMCD). Luminal ATP induced an increase in Ca(2+)
      signaling in native medullary CD (MCD) as measured by fluorescence imaging. ATP
      also induced an increase in Ca(2+) signaling in MCD cells grown in primary
      culture but not in the presence of P2XR antagonist PPNDS. Short circuit current
      (I(sc)) measurement with mouse IMCD cells showed that P2XR agonist BzATP induced
      a larger I(sc) than did P2YR agonist UTP in the apical membrane. Our data reveal
      for the first time that P2X(1) and P2X(4) are cell-specific with prominent
      immunoreactivity in the apical area of MCD cells. The finding that P2XR blockade
      inhibits ATP-induced Ca(2+) signaling suggests that activation of P2XR is a key
      step in Ca(2+)-dependent purinergic signaling. The result that activation of P2XR
      produces large I(sc) indicates the necessity of P2XR in renal CD ion transport.

PMID- 17560949
TI  - A basic review of psychiatric medical malpractice law in the United States.

PMID- 17560950
TI  - Clinical features of children and adolescents with obsessive-compulsive disorder
      and hoarding symptoms.
AB  - OBJECTIVE: This study was conducted to examine whether pediatric patients with
      obsessive-compulsive disorder (OCD) and hoarding symptoms differed in terms of
      clinical characteristics from pediatric OCD patients without hoarding symptoms.
      METHOD: Eighty children and adolescents with OCD (range, 7-17 years) completed
      clinician-administered and parent- and child-report measures of OCD symptom
      severity, impairment, and emotional and behavioral symptoms. RESULTS: Twenty-one
      youth endorsed significant hoarding symptoms. Relative to nonhoarders, youth with
      hoarding symptoms had worse insight, more magical thinking obsessions, and
      ordering/arranging compulsions than nonhoarders, higher levels of anxiety,
      aggression, somatic complaints, and overall externalizing and internalizing
      symptoms. Higher rates of panic disorder were found in youth with hoarding
      symptoms although other comorbidity rates did not differ. CONCLUSIONS: These
      findings in children are partially consistent with studies in adults, and suggest
      that pediatric patients with hoarding symptoms may exhibit a unique clinical
      presentation.

PMID- 17560951
TI  - Sex, timing, and depression among suicide victims with schizophrenia.
AB  - BACKGROUND: Schizophrenia and depression by themselves and especially in
      combination with each other are known to be important risk factors of suicide. An
      increased risk of suicide has also been reported for the period immediately after
      a psychiatric patient's discharge from the hospital. However, to the best of our
      knowledge, it remains unknown whether survival times differ between suicide
      victims with schizophrenia concomitantly with and those without depression.
      OBJECTIVE: This study aimed to examine survival times from the discharge of last
      hospital treatment (irrespective of the kind of illness) to the day of death in
      suicide victims with schizophrenia with or without concomitant depression.
      MATERIAL AND METHOD: A 16-year database of all suicides (1535 males, 342 females)
      committed during the years 1988-2003 in the province of Oulu in northern Finland,
      and information available from the national hospital discharge registers formed
      the basis of this study. RESULTS: In male suicide victims with schizophrenia, the
      median survival time after final hospitalization was approximately 1 day in those
      with a history of depression and 90 days in those without depression (P = .005).
      The corresponding times for females were 50 and 24 days, respectively (P = .396).
      Using Cox regression analysis after adjusting for confounders, we noticed a
      statistically significant difference in survival times from last hospitalization
      to suicide between depressive and nondepressive male patients with schizophrenia
      (hazard ratio, 1.80; 95% confidence interval, 1.04-3.11), but not females (hazard
      ratio, 0.72; 95% confidence interval, 0.34-1.53). CONCLUSION: Concomitant
      depression was markedly linked with shorter survival time in male suicide victims
      with schizophrenia after last hospitalization. Psychiatric inpatient facilities
      appear to be in a key position to establish suicide prevention programs for
      patients with schizophrenia, especially those with depression.

PMID- 17560952
TI  - Health-related quality of life and functioning in remitted bipolar I outpatients.
AB  - The aim of this study was to characterize the health-related quality of life (HR
      QOL) and functioning in 90 bipolar I remitted outpatients. According to
      Diagnostic and Statistical Manual of Mental Disorders IV remission specifiers,
      patients were categorized into 4 groups: group 1, fully remitted; group 2, less
      than 2 months remitted; group 3, with persisting manic symptoms; group 4, with
      persisting depressive symptoms. The severity of psychopathology was evaluated by
      using the Bech-Rafaelsen Mania-Melancholia Scale. The HR-QOL, functioning, and
      insight were assessed via the medical outcomes study 36-item short form, the
      global assessment of functioning scale, and the scale to assess unawareness of
      mental disorder, respectively. Fully remitted patients reported the highest
      scores in almost all domains of medical outcomes study 36-item short form, and
      had significantly higher scores on physical functioning, general health, social
      functioning, and mental health compared to patients with persisting depressive
      symptoms. Furthermore, patients with persisting manic symptoms reported
      significantly higher scores on general health, vitality and mental health than
      the group with persisting depressive symptoms. In contrast, the global assessment
      of functioning scale score differed among the 4 groups, with fully remitted
      patients reporting higher, although not statistically significant, scores than
      the other groups. Our data suggest that the persistence of depressive or manic
      symptoms seem to affect self-report measures of HR-QOL. An affectively biased
      cognition may explain the gap between patient's perception of functioning and
      estimated functional adjustment, as assessed by clinicians.

PMID- 17560953
TI  - Psychosocial impairment and treatment utilization by patients with borderline
      personality disorder, other personality disorders, mood and anxiety disorders,
      and a healthy comparison group.
AB  - This study compared psychosocial functioning and treatment utilization in 130
      participants who were diagnosed with a borderline personality disorder (BPD), a
      non-BPD personality disorder (OPD), a mood and/or anxiety disorder (MAD), or had
      no current psychiatric diagnosis and served as a healthy comparison group.
      Diagnostic and Statistical Manual of Mental Disorders (4th Edition) diagnoses,
      psychosocial functioning, and treatment utilization were determined by using well
      established semistructured research interviews conducted by trained doctoral
      level clinicians. Analysis of variance revealed the most severe deficits in
      functioning characterized the BPD group across areas of global functioning with
      more moderate impairments in functioning occurring in OPD and MAD groups. The BPD
      group was characterized by significantly greater psychiatric and nonpsychiatric
      treatment utilization than the other groups. These findings indicate that BPD as
      well as other personality disorders are a source of considerable psychologic
      distress and functional impairment equivalent to, and at times exceeding, the
      distress found in mood and anxiety disorders. The public health impact of BPD
      diagnosis is highlighted by the high rates of psychiatric and nonpsychiatric
      treatment utilization.

PMID- 17560954
TI  - Clinical dimensions of auditory hallucinations in schizophrenic disorders.
AB  - BACKGROUND: Auditory hallucinations occupy, along with delusional beliefs, the
      center stage of active or "positive" psychotic clinical psychopathology. During
      the last decade, several sets of auditory hallucinations' clinical features were
      subjected to multivariate statistical analyses to disclose major dimensions of
      psychotic patients' overall hallucinatory experience and behavior. However, these
      studies failed, to a large extent, to provide satisfactory external validations
      of the thereby extracted factors. METHODS: We investigated the major clinical
      dimensions of verbal auditory hallucinations in a sample of 100 inpatients with
      schizophrenic disorders. Patients (61 men and 39 women) were examined before the
      initiation of antipsychotic treatment and their assessment included 18 major
      clinical features of auditory hallucinations. Brief Psychiatric Rating Scale,
      Hamilton Depression Rating Scale, Global Assessment Scale, and Mini-Mental State
      Examination were used as external validators. RESULTS: Principal component
      analysis resulted in the extraction of 5 factors interpreted as the dimensions of
      severity of auditory hallucinations, emotional and behavioral impact, rate of
      their intrusion in self-consciousness, delusional elaboration, and similarity to
      ordinary auditory perception, respectively. The second and third factors
      extracted in our study correlated with short duration of illness, whereas the
      first, fourth, and fifth ones correlated with chronicity. Our second factor
      correlated with clinical severity of patients' current mental state, the fifth
      factor with severity of their cognitive impairment, and the first and fourth ones
      with lower clinical depression despite patients' chronicity. CONCLUSION: The
      findings of our study contribute to the further elucidation of the major clinical
      dimensions of auditory hallucinations and the testing of their external validity.

PMID- 17560955
TI  - Postpartum-onset major depression is associated with personality disorders.
AB  - OBJECTIVES: The objective of the study was to investigate the incidence rate of
      postpartum-onset major depression (PPMD) and to examine associated
      sociodemographic characteristics, obstetric factors, and personality disorders.
      METHOD: The study data were obtained from 302 women who delivered at a child and
      maternity hospital. We interviewed the new mothers on the first day of their
      childbirth and at 6 weeks postpartum. Major depression and axis II diagnoses were
      determined by means of the Structured Clinical Interview for the Diagnostic and
      Statistical Manual of Mental Disorders, Fourth Edition, and the Structured
      Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders,
      Revised Third Edition, Personality Disorders, respectively. RESULTS: Nineteen
      (6.3%) women had new-onset major depression during 6 weeks postpartum. Postpartum
      onset major depression was unrelated to age, educational level, employment
      status, planned or unplanned pregnancy, history of abortion and gestational
      complications, term of delivery, type of delivery, sex of the baby, and mother's
      breast-feeding. Frequency of primiparity and of avoidant, dependent, and
      obsessive-compulsive personality disorders was higher in women with PPMD than
      that in women without PPMD. As a result of logistic regression analysis, the
      independent predictor of PPMD was the presence of avoidant, dependent, and
      obsessive-compulsive personality disorders. CONCLUSION: Our results suggest that
      childbearing women with avoidant, dependent, and obsessive-compulsive personality
      disorders have increased risk of new-onset major depression during the postpartum
      period.

PMID- 17560956
TI  - The relationship between avoidant personality disorder and social phobia.
AB  - The main explanatory hypothesis for the distinction between social phobia (SP)
      and avoidant personality disorder (APD) has been the severity continuum
      hypothesis, stating that APD only differs from SP in terms of severity of
      dysfunction and symptomatic distress, that is, social anxiety and depressive
      symptoms. This study aimed at a comprehensive evaluation of this hypothesis in a
      large sample (n = 2192) of thoroughly assessed patients, most of whom had a
      diagnosis of personality disorder. Social phobia was stronger associated with APD
      than with other personality disorders, and APD was stronger associated with SP
      than with other symptom disorders. Social phobia-pure patients had a higher level
      of global functioning and lower levels of general symptom distress and
      interpersonal problems than APD-pure patients. The 2 groups were similar on
      domains that pertain to social anxiety and introversion, but APD was associated
      with a broader array of symptoms and interpersonal problems and was substantially
      lower on the personality domain of conscientiousness. Avoidant personality
      disorder was stronger associated with eating disorders, and SP was stronger
      associated with panic disorder. The APD diagnosis seems to capture a broader
      constellation of symptoms and personality features pointing toward more severe
      personality dysfunction. Our findings suggest that the severity continuum
      hypothesis lacks specificity and exploratory power to account for both
      similarities and differences between SP and APD.

PMID- 17560957
TI  - Dysfunctional cognitions in hospitalized patients with psychotic versus
      nonpsychotic major depression.
AB  - Previous research suggests that psychotic major depression (PMD) is associated
      with greater illness severity and functional impairment as well as poorer
      treatment response to antidepressants and psychotherapies compared with
      nonpsychotic major depression. Although patients with PMD exhibit a number of
      neurobiological abnormalities, little research has been conducted to date on
      possible psychological factors that are related to illness in this depression
      subtype. In the current study, baseline data were pooled from 2 clinical trials
      in which depressed patients (n = 235) were recruited during a psychiatric
      hospitalization for an acute episode. Twelve percent (n = 28) of this treatment
      seeking sample met criteria for PMD and showed elevated levels of depression
      severity and dysfunctional beliefs compared with individuals with nonpsychotic
      major depression. However, even after controlling for depression severity and
      other relevant baseline variables, only a measure of common dysfunctional beliefs
      differentiated those with vs those without psychotic features. Furthermore,
      higher levels of depressive cognitions were related to poorer psychosocial
      functioning and suicidality in PMD patients. Results suggest that elevated levels
      of common negative cognitions in depressed patients may be associated with the
      presence of more severe psychotic symptoms. Adapted cognitive-behavioral
      treatments may be useful for treating patients with PMD specifically.

PMID- 17560958
TI  - A comparison of the Tridimensional Personality Questionnaire in premenstrual
      dysphoric disorder and major depressive disorder.
AB  - OBJECTIVE: Numerous symptoms of premenstrual dysphoric disorder (PMDD) overlap
      with those of major depressive disorder (MDD). This study investigates
      differences in novelty seeking, harm avoidance, and reward dependence between
      patients with PMDD, MDD without premenstrual symptoms or premenstrual
      exacerbation, and normal control subjects. METHOD: The Chinese version of the
      Tridimensional Personality Questionnaire was administered to 51 PMDD, 39 MDD, and
      52 normal control women during the luteal phase (between the menstrual cycle days
      23 and 28). RESULTS: Harm avoidance score was significantly higher in women with
      MDD and PMDD than in controls, whereas reward dependence score was lower in women
      with MDD than in controls. However, Tridimensional Personality Questionnaire
      (except for the subscale of impulsiveness) did not distinguish between PMDD and
      MDD during the luteal phase. CONCLUSION: The similarities between PMDD and MDD
      during luteal phase suggest a similar psychopathology.

PMID- 17560959
TI  - Illness appraisals and self-esteem as correlates of anxiety and affective
      comorbid disorders in schizophrenia.
AB  - Comorbidity of anxiety and affective disorders in people with a diagnosis of
      schizophrenia is common. This study investigated the hypothesis that greater
      negative beliefs about illness and lower self-esteem will be significantly
      associated with the presence of anxiety or affective comorbidity in a sample of
      persons (n = 138) diagnosed with schizophrenia. The Structured Clinical Interview
      for the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition;
      the Positive and Negative Syndrome Scale; the Global Assessment of Functioning
      Scale; the Personal Beliefs about Illness Questionnaire; and the Rosenberg Self
      Esteem Scale were all completed for each participant. Of the total sample, 62
      (44.9%) had a comorbid anxiety or affective disorder. Logistic regression
      revealed that those with a comorbid anxiety or affective disorder had
      significantly lower levels of functioning (Global Assessment of Functioning),
      more negative appraisals of entrapment in psychosis (Personal Beliefs about
      Illness Questionnaire), and lower levels of self-esteem (Rosenberg Self-Esteem
      Scale). Although further research is required, the strong association between
      personal beliefs about self and illness and comorbidity suggests that negative
      beliefs about psychotic experiences and self-esteem may be linked to the
      development and maintenance of anxiety and affective comorbid conditions among
      people with a diagnosis of schizophrenia or the like.

PMID- 17560960
TI  - An analysis of the cognitive deficit of schizophrenia based on the Piaget
      developmental theory.
AB  - OBJECTIVE: The objective of the study was to evaluate from the perspective of the
      Piaget developmental model the cognitive functioning of a sample of patients
      diagnosed with schizophrenia. METHOD: Fifty patients with schizophrenia
      (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) and 40
      healthy matched controls were evaluated by means of the Longeot Logical Thought
      Evaluation Scale. RESULTS: Only 6% of the subjects with schizophrenia reached the
      "formal period," and 70% remained at the "concrete operations" stage. The
      corresponding figures for the control sample were 25% and 15%, respectively.
      These differences were statistically significant. The samples were specifically
      differentiable on the permutation, probabilities, and pendulum tests of the
      scale. CONCLUSIONS: The Longeot Logical Thought Evaluation Scale can discriminate
      between subjects with schizophrenia and healthy controls.

PMID- 17560961
TI  - Reliability and validity of the Italian version of the Temperament and Character
      Inventory-Revised in an outpatient sample.
AB  - OBJECTIVE: The aim of this study was to evaluate the reliability and validity of
      the Temperament and Character Inventory-Revised (TCI-R) in an outpatient sample.
      METHOD: The TCI-R was administered to 404 consecutively admitted subjects. The
      TCI-R scale 1-month test-retest reliability and TCI-R/TCI convergent validity
      were assessed in 2 independent subsamples. RESULTS: The TCI-R scales showed
      adequate Cronbach alpha values and acceptable 1-month test-retest reliability
      coefficients. Although many TCI-R facets showed factorial complexity, factor
      analysis results were consistent with the 7-factor structure of the TCI-R scales.
      The predictive validity of TCI-R profiles for personality disorder diagnoses was
      confirmed, with different combinations of temperament dimensions being associated
      with specific personality disorders. CONCLUSIONS: The TCI-R was a reliable and
      valid instrument for assessing temperament and character features, at least among
      Italian outpatients. The TCI-R psychometric properties support its clinical
      usefulness in the assessing of personality psychopathology.

PMID- 17560962
TI  - Childhood-onset pathologic skin picking: clinical characteristics and psychiatric
      comorbidity.
AB  - There has been little research examining clinical correlates of childhood-onset
      pathologic skin picking in a sample of individuals with a primary diagnosis of
      pathologic skin picking. Using a sample of 40 consecutive subjects with current
      pathologic skin picking, we compared subjects with childhood-onset (before 10
      years of age) pathologic skin picking to those with later onset on a variety of
      clinical measures. Symptom severity was examined by assessing time spent picking
      per day, intensity and frequency of thoughts and urges to pick, and social and
      occupational functioning. Of the 40 subjects, 19 (47.5%) reported onset of skin
      picking before 10 years of age. Subjects with childhood-onset had significantly
      longer durations of illness before receiving treatment and were more likely to
      pick unconsciously. Symptom severity, comorbidity, and social functioning did not
      differ between groups. These preliminary results suggest that although onset
      before 10 years of age is fairly common among people with pathologic skin
      picking, individuals developing this behavior earlier in life have similar
      clinical characteristics as those with later onset but may be less likely to seek
      treatment.

PMID- 17560963
TI  - Epothilone-paclitaxel resistant leukemic cells CEM/dEpoB300 are sensitive to
      albendazole: Involvement of apoptotic pathways.
AB  - Altered or deficient activation of apoptosis signalling pathways may contribute
      to drug resistance. Here, we assess the role of apoptotic mediators in eliciting
      an anti-proliferative response to paclitaxel (PTX) in a T cell acute
      lymphoblastic leukemia (ALL) cell line CEM and its epothilone-paclitaxel
      resistant sub-line CEM/dEpoB300. Furthermore, the cellular response to PTX was
      compared to those elicited by cells in response to treatment with albendazole
      (ABZ; a microtubule depolymerizing agent). In cell proliferation studies, CEM
      cells were sensitive to both PTX and ABZ, while the CEM/dEpoB300 cells were
      highly resistant to PTX (IC(50) 2.86 nM versus 30.26 nM, respectively). In
      contrast, the resistant cells showed a 2-fold increase in sensitivity to ABZ
      (0.32 microM in CEM compared to 0.16 microM in CEM/dEpoB300). Analysis of caspase
      3 activity and cytochrome c release in response to PTX or ABZ treatment (24, 48
      and 72 h) revealed that, compared to the parent cells, the resistant cells have
      diminished response to PTX and enhanced response to ABZ. A similar pattern was
      observed for the pro-apoptotic protein Bax. Levels of the anti-apoptotic protein
      Bcl-2 was highly elevated in CEM/dEpoB300 cells and in these cells, ABZ was more
      effective in lowering the Bcl-2 levels than PTX. Similarly, ABZ treatment led to
      profound down regulation of the Mcl-1 protein. These results reveal for the first
      time, the changes in apoptotic mediators following development of resistance to
      PTX in an ALL cell and the significantly increased sensitivity of these PTX
      resistant cells to ABZ.

PMID- 17560965
TI  - An inverse relation between event-related and time-frequency violation responses
      in sentence processing.
AB  - The relationship between semantic and grammatical processing in sentence
      comprehension was investigated by examining event-related potential (ERP) and
      event-related power changes in response to semantic and grammatical violations.
      Sentences with semantic, phrase structure, or number violations and matched
      controls were presented serially (1.25 words/s) to 20 participants while EEG was
      recorded. Semantic violations were associated with an N400 effect and a theta
      band increase in power, while grammatical violations were associated with a P600
      effect and an alpha/beta band decrease in power. A quartile analysis showed that
      for both types of violations, larger average violation effects were associated
      with lower relative amplitudes of oscillatory activity, implying an inverse
      relation between ERP amplitude and event-related power magnitude change in
      sentence processing.

PMID- 17560964
TI  - Nuclear migration during retinal development.
AB  - In this review we focus on the mechanisms, regulation, and cellular consequences
      of nuclear migration in the developing retina. In the nervous system, nuclear
      migration is prominent during both proliferative and post-mitotic phases of
      development. Interkinetic nuclear migration is the process where the nucleus
      oscillates from the apical to basal surfaces in proliferative neuroepithelia.
      Proliferative nuclear movement occurs in step with the cell cycle, with M-phase
      being confined to the apical surface and G1-, S-, and G2-phases occurring at more
      basal locations. Later, following cell cycle exit, some neuron precursors migrate
      by nuclear translocation. In this mode of cellular migration, nuclear movement is
      the driving force for motility. Following discussion of the key components and
      important regulators for each of these processes, we present an emerging model
      where interkinetic nuclear migration functions to distinguish cell fates among
      retinal neuroepithelia.

PMID- 17560966
TI  - Flk1(+) cardiac stem/progenitor cells derived from embryonic stem cells improve
      cardiac function in a dilated cardiomyopathy mouse model.
AB  - OBJECTIVES: Flk1(+) cells derived from embryonic stem (ES) cells are known to
      differentiate into mesodermal lineages such as hematopoietic and endothelial
      cells. Here we demonstrate that they can develop into cardiomyocytes that support
      functional recovery in a dilated cardiomyopathy (DCM) C57/BL6 mouse model.
      METHODS: Flk1(+) and Flk1(-) cells were sorted at day 4 of differentiation, and
      cardiomyogenesis was assessed in vitro. Next, we transplanted these cells into
      the hearts of cardiomyopathy mice to assess improvement in cardiac function.
      RESULTS: Flk1(+) cells, but not Flk1(-) cells, isolated on day 4 after
      differentiation were efficiently converted into contractile cardiomyocytes. RT
      PCR analysis and immunohistological assays demonstrated that contractile cells
      derived from Flk1(+) cells in vitro expressed mature cardiac markers on day 10
      after differentiation. Transplantation of sorted Flk1(+) cells into DCM model
      mouse hearts improved cardiac function, as determined by echocardiography and
      cardiac catheterization. The in vivo differentiated Flk1(+) cells expressed
      cardiac markers and had gap junctions, as demonstrated by immunohistochemistry.
      Furthermore, these cells generated ventricular type action potentials similar to
      those of adult ventricle. CONCLUSION: These results indicate that Flk1 is a good
      marker for sorting cardiac stem/progenitor cells which can differentiate into
      mature cardiomyocytes both in vitro and in vivo.

PMID- 17560967
TI  - Glycosaminoglycan synthesis and structure as targets for the prevention of
      calcific aortic valve disease.
AB  - Calcific aortic valve disease is frequently driven by ageing and the obesity
      associated metabolic syndrome, and the increasing impact of these factors
      indicates that valve disease will become a cardiovascular disease of considerable
      significance. This disease is now thought to be an active cell-based disease
      process, which may therefore be amenable to therapeutic intervention. Some
      similarities are apparent with atherosclerosis. The accumulation of lipid,
      possibly by retention by proteoglycans and the attraction of inflammatory cells
      by hyaluronan, may be common to the early stages of both pathologies. The
      synthesis and structure of glycosaminoglycans, proteoglycans, and hyaluronan are
      exquisitely regulated, and the signalling pathways controlling these processes
      may provide tissue-specific opportunities for concomitant prevention of
      atherosclerosis and calcific aortic valve disease.

PMID- 17560968
TI  - Diacylglycerols, multivalent membrane modulators.
AB  - Diacylglycerols are second messengers confined to biomembranes and, although
      relatively simple molecules from the structural point of view, they are able of
      triggering a surprisingly wide range of biological responses. Diacylglycerols are
      recognized by a well conserved protein motif, such as the C1 domain. This domain
      was observed for the first time in protein kinases C but is now known to be
      present in many other proteins. The effect of diacylglycerols is not limited to
      binding to C1 domains and they are able to alter the biophysical properties of
      biomembranes and hence modulate the activity of membrane associated proteins and
      also facilitate some processes like membrane fusion.

PMID- 17560969
TI  - Cognitive predictors of single-digit and procedural calculation skills and their
      covariation with reading skill.
AB  - This study examined the extent to which children's cognitive abilities in
      kindergarten and their mothers' education predict their single-digit and
      procedural calculation skills and the covariance of these with reading skill in
      Grade 4. In kindergarten, we assessed children's (N=178) basic number skills,
      linguistic skills, and visual attention. In Grade 4, we assessed their
      calculation and reading skills. Data on children's cognitive ability at 5 years
      of age and their mothers' level of education were also collected. The results
      showed that both of the core components of calculation, single-digit and
      procedural calculation, as well as their covariance with reading, were predicted
      by unique cognitive factors. Fluency in single-digit calculation and text reading
      shared an underlying cognitive process, that is, the ability to fluently retrieve
      verbal or visual-verbal associations from long-term memory. In contrast,
      procedural calculation was predicted not only by single-digit calculation but
      also by mother's education and conceptual knowledge of numbers. Overall, the
      results suggest that a multicomponential approach, including a hierarchical
      relation among various components, is fruitful when trying to understand the
      development of mathematical skill and its covariation with reading.

PMID- 17560970
TI  - Capillary blood, an alternative to saliva for the diagnosis of Cushing's
      syndrome?

PMID- 17560971
TI  - Gesturing makes learning last.
AB  - The gestures children spontaneously produce when explaining a task predict
      whether they will subsequently learn that task. Why? Gesture might simply reflect
      a child's readiness to learn a particular task. Alternatively, gesture might
      itself play a role in learning the task. To investigate these alternatives, we
      experimentally manipulated children's gesture during instruction in a new
      mathematical concept. We found that requiring children to gesture while learning
      the new concept helped them retain the knowledge they had gained during
      instruction. In contrast, requiring children to speak, but not gesture, while
      learning the concept had no effect on solidifying learning. Gesturing can thus
      play a causal role in learning, perhaps by giving learners an alternative,
      embodied way of representing new ideas. We may be able to improve children's
      learning just by encouraging them to move their hands.

PMID- 17560972
TI  - Interpretation of BMP signaling in early Xenopus development.
AB  - Very little is known about how the extracellular binding of a morphogen is
      transduced to the nucleus of a cell in a concentration-related way, enabling
      cells to interpret their position in a concentration gradient. Here, we have
      analyzed when and how Xenopus embryo cells perceive and interpret a BMP signal.
      Dissociated embryo cells are exposed for short times to different concentrations
      of BMP4. We find that cells are already competent to receive a BMP4 signal at the
      blastula stage. They phosphorylate Smad1 very rapidly and express downstream
      genes less than half an hour after exposure to BMP. However, Smad1 is present in
      the nucleus even in the absence of BMP. To quantitate intracellular signaling
      after BMP exposure, we have constructed a chimeric type I receptor that registers
      BMP signaling as the intranuclear migration of Smad2, and as the transcription of
      Smad2 downstream genes. The combination of the chimeric receptor and GFP-Smad2
      makes it possible to follow the transduction of BMP signaling to the nucleus.
      From our results, we conclude that an extracellular BMP concentration is
      interpreted by the steady state nuclear concentration of phosphorylated Smad1.

PMID- 17560973
TI  - The secreted cell signal Folded Gastrulation regulates glial morphogenesis and
      axon guidance in Drosophila.
AB  - During gastrulation in Drosophila, ventral cells change shape, undergoing
      synchronous apical constriction, to create the ventral furrow (VF). This process
      is affected in mutant embryos lacking zygotic function of the folded gastrulation
      (fog) gene, which encodes a putative secreted protein. Fog is an essential
      autocrine signal that induces cytoskeletal changes in invaginating VF cells. Here
      we show that Fog is also required for nervous system development. Fog is
      expressed by longitudinal glia in the central nervous system (CNS), and reducing
      its expression in glia causes defects in process extension and axon ensheathment.
      Glial Fog overexpression produces a disorganized glial lattice. Fog has a
      distinct set of functions in CNS neurons. Our data show that reduction or
      overexpression of Fog in these neurons produces axon guidance phenotypes.
      Interestingly, these phenotypes closely resemble those seen in embryos with
      altered expression of the receptor tyrosine phosphatase PTP52F. We conducted
      epistasis experiments to define the genetic relationships between Fog and PTP52F,
      and the results suggest that PTP52F is a downstream component of the Fog
      signaling pathway in CNS neurons. We also found that Ptp52F mutants have early VF
      phenotypes like those seen in fog mutants.

PMID- 17560974
TI  - Tamoxifen-inducible gene deletion reveals a distinct cell type associated with
      trabecular bone, and direct regulation of PTHrP expression and chondrocyte
      morphology by Ihh in growth region cartilage.
AB  - Indian hedgehog (Ihh) controls multiple aspects of endochondral skeletal
      development by signaling to both chondrocytes and perichondrial cells. Previous
      efforts to delineate direct effects of Ihh on chondrocytes by Col2-Cre-mediated
      ablation of Smoothened (Smo, encoding a transmembrane protein indispensable for
      Ihh signaling) has been only partially successful, due to the inability to
      discriminate between chondrocytes and perichondrial cells. Here we report a
      transgenic line (Col2-Cre) expressing under the control of the Colalpha1(II)
      promoter an inert form of Cre that is activatable by exogenous tamoxifen (TM); TM
      administration at proper times during embryogenesis induced Cre activity in
      chondrocytes but not in the perichondrium. By using this mouse line, we deleted
      Smo within subsets of chondrocytes without affecting the perichondrium and found
      that Smo removal led to localized disruption of the expression of parathyroid
      hormone-related protein (PTHrP) and the morphology of chondrocytes. Unexpectedly,
      TM invariably induced Cre activity in a subset of cells associated with the
      trabecular bone surface of long bones. These cells, when genetically marked and
      cultured in vitro, were capable of producing bone nodules. Expression of the Col2
      Cre transgene in these cells likely reflected the endogenous Colalpha1(II)
      promoter activity as similar cells were found to express the IIA isoform of
      Colalpha1(II) mRNA endogenously. In summary, the present study has not only
      provided evidence that Ihh signaling directly controls PTHrP expression and
      chondrocyte morphology in the growth region cartilage, but has also uncovered a
      distinct cell type associated with the trabecular bone that appears to possess
      osteogenic potential.

PMID- 17560975
TI  - Hox gene expression patterns in Lethenteron japonicum embryos--insights into the
      evolution of the vertebrate Hox code.
AB  - The Hox code of jawed vertebrates is characterized by the colinear and
      rostrocaudally nested expression of Hox genes in pharyngeal arches, hindbrain,
      somites, and limb/fin buds. To gain insights into the evolutionary path leading
      to the gnathostome Hox code, we have systematically analyzed the expression
      pattern of the Hox gene complement in an agnathan species, Lethenteron japonicum
      (Lj). We have isolated 15 LjHox genes and assigned them to paralogue groups (PG)
      1-11, based on their deduced amino acid sequences. LjHox expression during
      development displayed gnathostome-like spatial patterns with respect to the PG
      numbers. Specifically, lamprey PG1-3 showed homologous expression patterns in the
      rostral hindbrain and pharyngeal arches to their gnathostome counterparts.
      Moreover, PG9-11 genes were expressed specifically in the tailbud, implying its
      posteriorizing activity as those in gnathostomes. We conclude that these
      gnathostome-like colinear spatial patterns of LjHox gene expression can be
      regarded as one of the features already established in the common ancestor of
      living vertebrates. In contrast, we did not find evidence for temporal
      colinearity in the onset of LjHox expression. The genomic and developmental
      characteristics of Hox genes from different chordate species are also compared,
      focusing on evolution of the complex body plan of vertebrates.

PMID- 17560976
TI  - Tumorhead distribution to cytoplasmic membrane of neural plate cells is
      positively regulated by Xenopus p21-activated kinase 1 (X-PAK1).
AB  - Tumorhead (TH) regulates neural plate cell proliferation during Xenopus early
      development, and gain or loss of function prevents neural differentiation. TH
      shuttles between the nuclear and cytoplasmic/cortical cell compartments in
      embryonic cells. In this study, we show that subcellular distribution of TH is
      important for its functions. Targeting TH to the cell cortex/membrane potentiates
      a TH gain of function phenotype and results in neural plate expansion and
      inhibition of neuronal differentiation. We have found that TH subcellular
      localization is regulated, and that its shuttling between the nucleus and the
      cell cortex/cytoplasm is controlled by the catalytic activity of p21-activated
      kinase, X-PAK1. The phenotypes of embryos that lack, or have excess, X-PAK1
      activity mimic the phenotypes induced by loss or gain of TH functions,
      respectively. We provide evidence that X-PAK1 is an upstream regulator of TH and
      discuss potential functions of TH at the cell cortex/cytoplasmic membrane and in
      the nucleus.

PMID- 17560977
TI  - Membrane localization of the NlpC/P60 family protein EGL-26 correlates with
      regulation of vulval cell morphogenesis in Caenorhabditis elegans.
AB  - Vulval morphogenesis in Caenorhabditis elegans generates a stack of toroidal
      cells enclosing a tubular lumen. Mutation of egl-26 is associated with
      malformation of vulF, the most dorsal toroid in the stack, resulting in a blocked
      lumen and an egg-laying defect. Here we present evidence that vulF retains the
      expected gene expression pattern, functions in signaling to the uterus and
      retains proper polarity when egl-26 is mutated, all suggesting that mutation of
      egl-26 specifically results in aberrant morphogenesis as opposed to abnormal fate
      specification. Recent computational analysis indicates that EGL-26, which was
      previously characterized as novel, belongs to the LRAT (lecithin retinol
      acyltransferase) subfamily of the NlpC/P60 superfamily of catalytic proteins. Via
      site-directed mutagenesis, we demonstrate a requirement of the putative catalytic
      residues for EGL-26 function in vivo. We also show that mutation of conserved
      serine 275 perturbs the apical membrane localization and the function of the EGL
      26 protein. Additional mutagenesis of this residue suggests that EGL-26 attains
      its membrane localization via a mechanism distinct from that of LRAT.

PMID- 17560979
TI  - Surgical therapy of liver metastases.
AB  - The liver is the most common site of metastatic disease from both
      gastrointestinal and extra-intestinal malignancies. Historically, only a minority
      of patients with colorectal liver metastases were candidates for resection.
      However, over the past several decades, liver resection has evolved as a safe and
      potentially curative treatment for hepatic colorectal metastases. The development
      of active chemotherapy and molecular targeted therapies, together with newer
      modalities like radiofrequency ablation, have expanded the indications for
      hepatic resection and improved survival. Selected patients with isolated liver
      metastases from neuroendocrine tumors, germ cell cancers, ocular melanoma,
      gastrointestinal stromal tumors (GIST), and breast cancer also may be considered
      for hepatic surgery.

PMID- 17560980
TI  - Surgical therapy of lung metastases.
AB  - Almost 125 years after the first documented case, pulmonary metastasectomy is
      still poorly understood. No other organ is subject to the wide histologic variety
      of metastatic insults, and this fact has complicated a complete exposition of
      when pulmonary metastasectomy may be beneficial. Many physicians still consider
      pulmonary metastatic disease to be always incurable, and they may underestimate
      existing surgical options including the benefits of pulmonary metastasectomy. In
      addition, technological improvements in radiological screening of pulmonary
      metastases and thoracoscopic resection are fundamentally altering the management
      of these patients and their surgery. This article reviews the history, form, and
      future of pulmonary metastasectomy, the literature that supports or refutes its
      application in various tumor types, and the screening and surgical evaluation
      that is needed prior to its performance.

PMID- 17560981
TI  - Surgical therapies in brain metastasis.
AB  - Brain metastases are the most common intracranial tumors in adults and source of
      the most common neurological complications of systemic cancer. The treatment
      approach to brain metastases differs essentially from treatment of systemic
      metastases due to the unique anatomical and physiological characteristics of the
      brain. Surgery and radiosurgery are important components in the complex treatment
      of brain metastases and can prolong survival and improve the quality of life
      (QOL). Aggressive intervention may be indicated for selected patients with well
      controlled systemic cancer and good performance status in whom central nervous
      system (CNS) disease poses the greatest threat to functionality and survival. In
      this review the respective roles of surgery and radiosurgery, patient selection,
      general prognostic factors and tailoring of optimal surgical management
      strategies for cerebral metastases are discussed.

PMID- 17560982
TI  - Surgical therapy of bone metastases.
AB  - The treatment of patients with cancer epitomizes the importance of using a
      collaborative team approach to optimize patient care. Physician team members most
      commonly are radiation oncologists, general surgeons, surgical oncologists,
      thoracic surgeons, neurosurgeons, and orthopedic surgeons. When patients are
      receiving chemotherapy, their medical oncologist frequently takes responsibility
      for coordinating care among the various team members and initiating consultations
      with necessary providers. When patients develop bone metastases or chemotherapy
      induced bone loss (CTIBL), the orthopedic surgeon may be able to improve the
      patient's quality of life greatly. Procedures orthopedists perform most commonly
      include open reduction and internal fixations and arthroplasties (joint
      replacement surgery). Less invasive procedures currently being tested include
      stereotactic radiosurgery, radiofrequency ablation (RFA), and percutaneous
      cementoplasty. By understanding the options available to patients with skeletal
      complications of malignancy, the medical oncologist can discuss issues with
      patients and make appropriate referrals for diagnosis and treatment.
      Additionally, with a greater understanding of the surgical procedures available,
      the medical oncologist will be better able to assist in preparing the patient for
      surgery.

PMID- 17560983
TI  - Surgical management of metastatic peritoneal or pleural disease.
AB  - The surgeon's role in the treatment of malignant peritoneal disease has expanded
      over time, stemming from a better understanding of tumor biology. For the
      majority of patients, carcinomatosis is a terminal process with surgical
      intervention being reserved for palliation of bowel obstruction or symptomatic
      ascites. However, for select patients with favorable tumor biologies, aggressive
      surgical approaches may result in long-term survival. This review describes the
      patterns of peritoneal tumor dissemination, surgical palliation of malignant
      bowel obstruction or ascites, and the principles, indications, toxicities, and
      overall results of cytoreductive surgery with intraperitoneal hyperthermic
      chemotherapy. On the other hand, long-term survival is rarely expected for
      malignant pleural disease unless the causal tumor is highly responsive to
      systemic chemotherapy. There are controversies and considerable geographic
      variations in the management of malignant pleural effusions. However, less
      invasive ambulatory palliative treatments for patients so afflicted are gaining
      popularity.

PMID- 17560984
TI  - Surgical management of women with ovarian cancer.
AB  - Ovarian carcinoma remains a leading cause of cancer-related death among women.
      Proper treatment of ovarian cancer begins with a thorough staging operation and
      attempt to totally debulk tumor sites. Despite even maximal surgical efforts,
      most patients with ovarian cancer require systemic or intraperitoneal
      chemotherapy. Even though aggressive therapies are effective for the treatment of
      ovarian cancer, recurrence of the disease is common and often necessitates
      salvage surgical procedures and chemotherapy.

PMID- 17560985
TI  - Surgical management of breast cancer.
AB  - Breast cancer treatment outcomes have improved as a result of early detection and
      multidisciplinary treatment approaches. Treatment options continue to expand as
      understanding increases regarding the relationship between disease burden,
      biology, and outcome. In this article we present the current principles and
      challenges that face the clinician who is treating breast disease. Better
      understanding of the biology of high-risk lesions and the significance of minimal
      metastatic disease permits better treatment. Advances in reconstructive surgery,
      continued refinement of resection techniques, and the management of less common
      presentations of breast cancer are presented.

PMID- 17560986
TI  - Surgical management of rectal cancer.
AB  - Rectal cancer affects more than 40,000 people in the United States annually.
      Despite recent advances in radiation and chemotherapy, surgical resection remains
      an integral part of curative therapy for this disease. Although rectal cancer is
      thought to be biologically similar to colon cancer, the anatomic complexity of
      the pelvis makes therapy for this disease considerably more complicated. Local
      recurrence is also a greater concern in rectal cancer than in colon cancer. The
      choice of surgical therapy depends on the location of the tumor, depth of rectal
      wall invasion, and clinical stage. Surgical options include local excision
      (transanal excision and transanal endoscopic microsurgery) and radical resection
      (low anterior resection, extended low anterior resection with coloanal
      anastomosis, abdominoperineal resection [APR], and pelvic exenteration).
      Technical advances such as transanal endoscopic microsurgery and laparoscopy also
      are changing the surgical approach to rectal tumors. Finally, chemotherapy and
      radiation are now frequently recommended in conjunction with surgical therapy.
      This article reviews the current surgical approach to treating patients with
      rectal cancer.

PMID- 17560987
TI  - Surgical management of primary lung cancer.
AB  - Despite advancements in systemic treatment and the understanding of tumor
      biology, the mainstay for the treatment of lung cancer remains its resection. All
      patients with lung cancer should be considered surgical candidates until they are
      proven to have contraindications to resection. This article reviews preoperative
      assessment and the operative technique for the surgical treatment of lung cancer.
      As with other surgical specialties, thoracic surgery is moving towards minimally
      invasive techniques that are reducing morbidity, mortality, and length of stay.
      This advance is allowing patients an earlier recovery from major pulmonary
      surgery.

PMID- 17560988
TI  - Local management of adult soft tissue sarcomas.
AB  - Soft tissue sarcomas (STS) are rare tumors classified into multiple histological
      subtypes and categorized into four sites: extremity and trunk, head and neck,
      retroperitoneal, and visceral, the latter now predominantly consisting of
      gastrointestinal stromal tumors. Well-planned, complete surgical resection is the
      mainstay of curative therapy for tumors at each of these sites. The success of
      surgery alone in controlling disease varies with the site, histologic grade,
      depth, and size of the tumor. For high-risk tumors, adjuvant therapy should be
      considered. In high-risk extremity tumors, adjuvant radiation has been proven in
      randomized trials to improve local control. Limb-sparing surgery combined with
      adjuvant radiation achieves equivalent local control to amputation, with the same
      distant relapse-free survival. Due to anatomical constraints, tumors of the head
      and neck and retroperitoneum are typically excised with close margins, providing
      a rationale for adjuvant radiation; the available evidence suggests but does not
      prove a benefit. Large-scale trials of adjuvant imatinib for gastrointestinal
      stromal tumors are currently being conducted. For tumors of the extremity/trunk,
      head and neck, and retroperitoneum, biopsy prior to definitive resection is
      recommended to establish the diagnosis and permit intelligent treatment planning
      with appropriate choice and sequencing of adjuvant therapies. This planning is
      most expeditiously done through multidisciplinary consultation at an experienced
      sarcoma center.

PMID- 17560989
TI  - Surgical therapy of cutaneous melanoma.
AB  - For most solid tumors therapy has evolved from surgery alone to a
      multidisciplinary approach. Malignant melanoma remains an exception, with surgery
      maintaining the principal role not only for treatment of the primary lesion but
      also staging and the management of advanced disease. The surgical management of
      melanoma has evolved over the years, resulting in a substantial decrease in the
      morbidity associated with treatment without a compromise in outcome. This article
      will review the changes that have occurred leading to the current surgical
      approach to melanoma, the evidence behind these recommendations, and new
      questions that need to be addressed.

PMID- 17560990
TI  - Pesticide exposure among farm workers.

PMID- 17560992
TI  - Hibernating myocardium: diagnosis and patient outcomes.
AB  - Approximately 50% of the patients with chronic obstructive coronary artery
      disease resulting in chronic contractile dysfunction have hibernating myocardium
      and may benefit from revascularization. This pooled analysis describes the
      relative merits of dobutamine echocardiography, thallium-201 and technetium-99m
      scintigraphy, positron emission tomography, and magnetic resonance imaging, for
      the diagnosis of hibernating myocardium and prediction of patient outcomes.

PMID- 17560993
TI  - Mechanisms of relaxing response induced by rat/mouse hemokinin-1 in porcine
      coronary arteries: roles of potassium ion and nitric oxide.
AB  - Rat and mouse hemokinin-1(r/m hemokinin-1) is a recently described member of the
      tachykinin family whose cardiovascular functions are not fully understood. In
      this study, we investigated the mechanisms of the relaxing response induced by
      r/m hemokinin-1 in isolated porcine coronary arteries by using a specific
      antagonist of tachykinin NK(1) receptor (SR140333), a nitric oxide synthase
      inhibitor N(omega)-nitro-L-arginine (L-NNA), and 1H-[1,2,4] Oxadiazolo [4,3-a]
      quinoxalin-1-one (ODQ), a blocker of cGMP production. r/m Hemokinin-1 (10(-12)
      10(-6 )M) evoked a marked endothelium-dependent vasodilatation (E(max)=121.12+/
      10.6% and 91.79+/-2.39% in 10(-6) M PGF(2)alpha and 30 mM KCl precontracted
      arterial rings, respectively) of coronary arteries mediated by activation of
      endothelial tachykinin NK(1) receptors. Two components contributed to this r/m
      hemokinin-1-elicited vasodilatation, the first of which was endothelium-derived
      hyperpolarizing factor (EDHF), which played a major role. This EDHF was
      identified as a potassium current through certain kinds of potassium channels on
      the endothelial cell membrane of porcine coronary arteries. Specific antagonists
      of Ca(2+)-activated K(+) channels (dequalinium and clotrimazole) did not have an
      inhibitory effect on the r/m hemokinin-1-induced vasodilatation, whereas they did
      on the substance P-induced vasodilatation. When potassium ion efflux was impaired
      by a high K(+) concentration (30 mM) or removal of K(+) from the surroundings, NO
      synthesis was triggered by r/m hemokinin-1 to produce an equivalent EDHF (K(+))
      independent vasorelaxation as a compensatory mechanism.

PMID- 17560994
TI  - Phospholipase D-dependent and -independent p38MAPK activation pathways are
      required for superoxide production and chemotactic induction, respectively, in
      rat neutrophils stimulated by fMLP.
AB  - Mitogen-activated protein kinase (MAPK)-mediated signal transduction pathways
      convert signals by extracellular stimulation into a variety of cellular
      functions. However, the roles of MAPKs in neutrophils are not well understood. To
      elucidate the temporal roles of p38MAPK during rat neutrophil activation
      stimulated by N-formyl-methionyl-leucyl-phenylalanine (fMLP), we examined the
      kinetics of this enzyme and the role of p38MAPK related to neutrophil functions
      (superoxide production and chemotaxis). SB203580, a potent and specific inhibitor
      of p38MAPK, significantly depressed both superoxide production and chemotaxis.
      Ethanol and 1-butanol, inhibitors of phospholipase D (PLD), suppressed p38MAPK
      activation in neutrophils under conditions (1 microM fMLP for 5 min) that
      stimulated superoxide production; and they significantly depressed superoxide
      production in rat neutrophils stimulated by fMLP. However, neither inhibitor had
      any effect on the activation of p38MAPK under the conditions (10 nM fMLP for 60
      min) that gave optimal chemotaxis. These results indicate that multiple signaling
      pathways were involved in stimulating p38MAPK and that p38MAPK played different
      roles in regulating neutrophil function depending on the conditions for
      stimulation with fMLP. In addition, the activation of p38MAPK occurred dependent
      on or independent of PLD activation in neutrophils stimulated with fMLP.

PMID- 17560995
TI  - Multiple mechanisms underlying the anticancer action of nanocrystalline
      fullerene.
AB  - Using the rat glioma cell line C6 and the human glioma cell line U251, we
      demonstrate the multiple mechanisms underlying the in vitro anticancer effects of
      the C(60) fullerene water suspension (nano-C(60) or nC(60)) produced by solvent
      exchange method. Nano-C(60) in a dose-dependent manner reduced the tumor cell
      numbers after 24 h of incubation. The observed antiglioma action of nC(60) at
      high concentration (1 microg/ml) was due to a reactive oxygen species-mediated
      necrotic cell damage that was partly dependent on oxidative stress-induced
      activation of extracellular signal-regulated kinase (ERK). On the other hand, low
      dose nC(60) (0.25 microg/ml) did not induce either necrotic or apoptotic cell
      death, but caused oxidative stress/ERK-independent cell cycle block in G(2)/M
      phase and subsequent inhibition of tumor cell proliferation. Treatment with
      either high-dose or low-dose nC(60) caused the appearance of acidified
      intracytoplasmic vesicles indicative of autophagy, but only the antiglioma effect
      of low-dose nC(60) was significantly attenuated by inhibiting autophagy with
      bafilomycin A1. Importantly, primary rat astrocytes were less sensitive than
      their transformed counterparts to a cytostatic action of low-dose nC(60). These
      data provide grounds for further development of nC(60) as an anticancer agent.

PMID- 17560996
TI  - Notch signaling induces SKP2 expression and promotes reduction of p27Kip1 in T
      cell acute lymphoblastic leukemia cell lines.
AB  - In T-cell acute lymphoblastic leukemia (T-ALL) NOTCH 1 receptors are frequently
      mutated. This leads to aberrantly high Notch signaling, but how this translates
      into deregulated cell cycle control and the transformed cell type is poorly
      understood. In this report, we analyze downstream responses resulting from the
      high level of NOTCH 1 signaling in T-ALL. Notch activity, measured immediately
      downstream of the NOTCH 1 receptor, is high, but expression of the canonical
      downstream Notch response genes HES 1 and HEY 2 is low both in primary cells from
      T-ALL patients and in T-ALL cell lines. This suggests that other immediate Notch
      downstream genes are activated, and we found that Notch signaling controls the
      levels of expression of the E3 ubiquitin ligase SKP2 and its target protein
      p27Kip1. We show that in T-ALL cell lines, recruitment of NOTCH 1 intracellular
      domain (ICD) to the SKP2 promoter was accompanied by high SKP2 and low p27Kip1
      protein levels. In contrast, pharmacologically blocking Notch signaling reversed
      this situation and led to loss of NOTCH 1 ICD occupancy of the SKP2 promoter,
      decreased SKP2 and increased p27Kip1 expression. T-ALL cells show a rapid G1-S
      cell cycle transition, while blocked Notch signaling resulted in G0/G1 cell cycle
      arrest, also observed by transfection of p27Kip1 or, to a smaller extent, a
      dominant negative SKP2 allele. Collectively, our data suggest that the aberrantly
      high Notch signaling in T-ALL maintains SKP2 at a high level and reduces p27Kip1,
      leading to more rapid cell cycle progression.

PMID- 17560997
TI  - Role of HIV-1 Vpr-induced apoptosis on the release of mitochondrial lysyl-tRNA
      synthetase.
AB  - Mitochondrial lysyl-tRNA synthetase (LysRS) is thought to be involved in the
      specific packaging of tRNA(3)(Lys) into HIV-1 viral particles. The HIV-1
      auxiliary viral protein Vpr is an apoptogenic protein that affects the integrity
      of the mitochondrial membrane and has also been reported to interact with LysRS.
      In the present study, we show that HIV-1 Vpr expressed in E. coli and purified to
      homogeneity does not interact specifically with LysRS and does not impact its
      aminoacylation activity. However, we also show that the mitochondrial
      localization of LysRS in HeLa cells is altered after addition of Vpr in the
      culture medium. These results suggest that HIV-1 Vpr fulfills an essential role
      in the process of packaging of mitochondrial LysRS.

PMID- 17560998
TI  - Identification and characterization of RED120: a conserved PWI domain protein
      with links to splicing and 3'-end formation.
AB  - Precursor (pre)-mRNA splicing can impact the efficiency of coupled steps in gene
      expression. SRm160 (SR-related nuclear matrix protein of 160 kDa), is a splicing
      coactivator that also functions as a 3'-end cleavage-stimulatory factor. Here, we
      have identified an evolutionary-conserved SRm160-interacting protein, referred to
      as hRED120 (for human Arg/Glu/Asp-rich protein of 120 kDa). hRED120 contains a
      conventional RNA recognition motif and, like SRm160, a PWI nucleic acid binding
      domain, suggesting that it has the potential to bridge different RNP complexes.
      Also, similar to SRm160, hRED120 associates with snRNP components, and remains
      associated with mRNA after splicing. Simultaneous suppression in Caenorhabditis
      elegans of the ortholog of hRED120 with the orthologs of splicing and 3'-end
      processing factors results in aberrant growth or developmental defects. These
      results suggest that RED120 may function to couple splicing with mRNA 3'-end
      formation.

PMID- 17560999
TI  - Chimeric retrogenes suggest a role for the nucleolus in LINE amplification.
AB  - Chimeric retrogenes, found in mammalian and fungal genomes, are bipartite
      elements composed of DNA copies of cellular transcripts either directly fused to
      each other or fused to the 3' part of a LINE retrotransposon. These cellular
      transcripts correspond to messenger RNAs, ribosomal RNAs, small nuclear RNAs and
      7SL RNA. The chimeras are likely formed by RNA template switches during reverse
      transcription of LINE elements by their retrotranspositional machinery. The 5'
      part of chimeras are copies of nucleolar RNAs, suggesting that the nucleolus
      plays a significant role in LINE retrotransposition. RNAs from the nucleolus
      might have protective function against retroelement invasion or, alternatively,
      the nucleolus may be required for retrotranspositional complex assembly and
      maturation. These hypotheses will be discussed in this review.

PMID- 17561000
TI  - PAI-1 deficiency reduces liver fibrosis after bile duct ligation in mice through
      activation of tPA.
AB  - Plasminogen activator inhibitor-1 (PAI-1) increases injury in several liver, lung
      and kidney disease models. The objective of this investigation was to assess the
      effect of PAI-1 deficiency on cholestatic liver fibrosis and determine PAI-1
      influenced fibrogenic mechanisms. We found that PAI-1(-/-) mice had less fibrosis
      than wild type (WT) mice after bile duct ligation. This change correlated with
      increased tissue-type plasminogen activator (tPA) activity, and increased matrix
      metalloproteinase-9 (MMP-9), but not MMP-2 activity. Furthermore, there was
      increased activation of the tPA substrate hepatocyte growth factor (HGF), a known
      anti-fibrogenic protein. In contrast, there was no difference in hepatic
      urokinase plasminogen activator (uPA) or plasmin activities between PAI-1(-/-)
      and WT mice. There was also no difference in the level of transforming growth
      factor beta 1 (TGF-beta1), stellate cell activation or collagen production
      between WT and PAI-1(-/-) animals. In conclusion, PAI-1 deficiency reduces
      hepatic fibrosis after bile duct obstruction mainly through the activation of tPA
      and HGF.

PMID- 17561001
TI  - gamma-Glutamyl transpeptidase GGT4 initiates vacuolar degradation of glutathione
      S-conjugates in Arabidopsis.
AB  - The xenobiotic monochlorobimane is conjugated to glutathione in the cytosol of
      Arabidopsis thaliana, transported to the vacuole, and hydrolyzed to cysteine S
      bimane [Grzam, A., Tennstedt, P., Clemens, S., Hell, R. and Meyer, A.J. (2006)
      Vacuolar sequestration of glutathione S-conjugates outcompetes a possible
      degradation of the glutathione moiety by phytochelatin synthase. FEBS Lett. 580,
      6384-6390]. The work here identifies gamma-glutamyl transpeptidase 4 (At4g29210,
      GGT4) as the first step of vacuolar degradation of glutathione conjugates.
      Hydrolysis of glutathione S-bimane is blocked in ggt4 null mutants of A.
      thaliana. Accumulation of glutathione S-bimane in mutants and in wild-type plants
      treated with the high affinity GGT inhibitor acivicin shows that GGT4 is required
      to initiate the two step hydrolysis sequence. GGT4:green fluorescent protein
      fusions were used to demonstrate that GGT4 is localized in the lumen of the
      vacuole.

PMID- 17561002
TI  - The additional value of ovarian hyperstimulation in intrauterine insemination for
      couples with an abnormal postcoital test and a poor prognosis: a randomized
      clinical trial.
AB  - OBJECTIVE: To assess the effectiveness of controlled ovarian hyperstimulation
      (COH) in intrauterine insemination (IUI) for subfertile couples with an abnormal
      postcoital test and a poor prognosis. DESIGN: Randomized clinical trial. SETTING:
      Twenty-four fertility centers in the Netherlands. PATIENT(S): Subfertile couples
      with a well-timed nonprogressive PCT and additional factors that reduce
      fertility. INTERVENTION(S): Couples were randomly allocated to three cycles of
      IUI with COH or three cycles of IUI without COH. MAIN OUTCOME MEASURE(S): Ongoing
      pregnancy within three IUI cycles. RESULT(S): We randomly allocated 132 couples
      to IUI with COH, and 133, to IUI without COH. We observed 33 pregnancies (25%) in
      the couples allocated to IUI with COH, of which 28 were ongoing (21%), vs. 28
      pregnancies (21%) in the couples allocated to IUI without COH, of which 23 were
      ongoing (17%; relative risk of an ongoing pregnancy, 1.2; 95% confidence
      interval, 0.75 to 2.0). Two multiple pregnancies occurred in the IUI with COH
      group, and one, in the IUI without COH group. CONCLUSION(S): In couples with an
      abnormal PCT and a poor prognosis, IUI with COH leads to pregnancy rates
      comparable to those for IUI without COH. We propose to perform IUI without COH in
      couples with an abnormal PCT.

PMID- 17561003
TI  - Changes in expression of P2X1 receptors and connexin 43 in the rat myometrium
      during pregnancy.
AB  - OBJECTIVE: To investigate the expression of P2X(1) receptors and connexin 43 in
      gap junctions between smooth muscle cells. Contraction mediated by P2X receptors
      is known to occur in the bladder and male reproductive tract, and cell-cell
      coupling of smooth muscle via gap junctions is essential for synchronized
      rhythmic activity of these tissues. DESIGN: We selected for this study rat
      myometrial smooth muscle during pregnancy and at postpartum day l. SETTING:
      University medical school. ANIMAL(S): Laboratory rats. INTERVENTION(S): Rats were
      mated and became pregnant. MAIN OUTCOME MEASURE(S): Immunostaining and
      fluorescence and confocal microscopy. RESULT(S): The level of P2X(1) receptor
      expression remained low throughout pregnancy (days 4 to 20) but was greatly up
      regulated at day 22 (postpartum day 1). Connexin 43 expression showed a pattern
      of up-regulation, with progression through pregnancy and peaking near labor, but
      exhibited a rapid down-regulation after parturition. CONCLUSION(S): The
      functional significance of the changes in connexin 43 and P2X(1) receptor
      expression that have been observed is discussed in relation to triggering and
      modulation of uterine contractility during and after pregnancy.

PMID- 17561004
TI  - Assessment of three-dimensional sonographic features of polycystic ovaries after
      laparoscopic ovarian electrocautery.
AB  - BACKGROUND: Treatment of polycystic ovary syndrome-related infertility includes
      laparoscopic ovarian electrocautery. Three-dimensional (3-D) sonographic
      characterization of polycystic ovaries has been performed recently, including the
      study of the effect of laparoscopic ovarian drilling on ovarian volume. The
      impact of laparoscopic treatment on ovarian volume and vascular flow-patterns
      assessed by 3-D color power angiography (CPA), however, has not yet been
      elucidated. OBJECTIVE: To measure ovarian volume, to evaluate and quantify
      intraovarian blood flow with 3-D CPA histogram analysis before and after
      laparoscopic ovarian electrocautery, and to compare the hormonal effects of
      surgery with 3-D sonographic findings. SETTING: University hospital. PATIENT(S):
      Ten patients, aged 18-34 years, with polycystic ovary syndrome. INTERVENTION(S):
      Evaluation of serum and urinary hormone profiles as well as transvaginal 3-D
      ultrasonography were performed before and after laparoscopic ovarian surgery.
      RESULT(S): Ovarian volume decreased, and 3-D CPA showed increased intraovarian
      flow intensity after laparoscopic electrocautery. Serum LH and T levels, ratios
      of urinary steroids reflecting 5 alpha-reductase enzyme activity, and androgen to
      cortisol metabolites decreased; serum FSH levels increased 1 week after
      laparoscopy and correlated well with changes of 3-D sonographic features. Seven
      patients ovulated regularly after surgery, and five pregnancies were conceived
      within 1 year. CONCLUSION(S): Three-dimensional ultrasonography may be a useful
      adjunct and noninvasive method for correlating clinical parameters with the blood
      flow alterations in polycystic ovary syndrome patients.

PMID- 17561005
TI  - Economics may not explain Hispanic underutilization of assisted reproductive
      technology services.
AB  - In a lower cost, equal-access-to-care setting, Hispanic use of assisted
      reproductive technology was less than half of what would have been expected based
      on patient demographics. Despite this use disparity, there were no significant
      differences between Hispanic and Caucasian women with regard to infertility
      diagnoses, assisted reproductive technology cycle parameters, clinical pregnancy
      rates, live birth rates, spontaneous abortion rates, and implantation rates.

PMID- 17561006
TI  - Effects of melatonin on the endometrial morphology and embryo implantation in
      rats.
AB  - OBJECTIVE: To determine the effects of melatonin on rat endometrium morphology
      and embryo implantation. DESIGN: Experimental study. SETTING: Federal University
      of Sao Paulo, Brazil. ANIMAL(S): Forty female rats. INTERVENTION(S): GI: control,
      GII: sham-operated, GIII: pinealectomized, and GIV: pinealectomized rats that
      received melatonin during 3 months. The GI, GII, and GIII groups received the
      vehicle of melatonin (NaCl + ethanol). At the end of the treatment, the animals
      were killed during the estrous phase; the uterus was removed for morphometric
      analysis. Urine was collected for 6-sulfatoxymelatonin. Blood was collected for
      estrogen (E) and progesterone (P) level determinations. In a second experiment,
      female rats were used to evaluate the endometrial embryo implantation. MAIN
      OUTCOME MEASURE(S): Endometrial morphology and embryo implantation. RESULT(S):
      GIII presented the highest values for endometrial area and thickness index,
      number of endometrial glands, and eosinophils. The number of vessels of groups I,
      II, and IV was fewer than that of GIII. The highest number of eosinophils was
      detected in GIII in comparison to other groups. The implantation rate in GIII was
      the lowest of all groups. This implantation rate was significantly increased and
      restored toward normal in GIV. CONCLUSION(S): Our data suggested that, in
      nonphotoperiodic animals such as rats, melatonin may positively affect the
      endometrial morphology and improve embryo implantation.

PMID- 17561007
TI  - Prolactinoma presenting as a failed vasectomy reversal.
AB  - OBJECTIVE: To present a case of prolactinoma presenting as a failed vasectomy
      reversal. DESIGN: Case report. SETTING: University-affiliated teaching hospital.
      PATIENT(S): A 46-year-old male with severe oligospermia after bilateral
      vasovasostomy and his 31-year-old female partner who had normal cycles.
      INTERVENTION(S): Bromocriptine, carbegoline, and l IVF. MAIN OUTCOME MEASURE(S):
      Correction of hyperprolactinoma, improved semen analysis, and pregnancy achieved
      by assisted reproductive technologies. RESULT(S): Semen analysis showing low
      volume (0.65 mL) and severe oligospermia (16 sperm) with zero motility on
      presentation. Endocrine evaluation showed prolactin of 650 ng/mL, T 0.37 ng/mL,
      and FSH 2.0 mIU/mL. A head CT scan showed a 1.2 cm pituitary adenoma. This was
      managed initially with bromocriptine, but due to side effects he was switched to
      carbegoline. In 1 month his PRL decreased to 16.9 ng/mL. Testosterone and FSH
      normalized. Repeat semen analysis after 5 months showed a volume of 4.5 mL and a
      concentration of 15 million/mL with 1% motility. Antisperm antibodies were
      positive. Because of antisperm antibodies and oligoasthenospermia,
      intracytoplasmic sperm injection with ejaculated sperm and, later, testicular
      extraction, were attempted without success. Donor sperm was eventually used.
      CONCLUSION(S): This is the first reported case of prolactinoma as a cause of
      infertility after vas reversal and demonstrates that not all cases of suspected
      failed vasectomy reversals are due to recurrent obstruction.

PMID- 17561008
TI  - A combined intrauterine and cervical pregnancy diagnosed in the 13th gestational
      week: which type of management is more feasible and successful?
AB  - OBJECTIVE: To present a case of a simultaneous nonviable cervical pregnancy and
      viable intrauterine pregnancy diagnosed in the 13th gestational week and to
      discuss the possible therapeutic options. DESIGN: Case report. SETTING:
      University hospital of Munster, Germany. PATIENT(S): A 40-year-old woman who had
      undergone IVF-embryo transfer because of previous surgical sterilization.
      INTERVENTION(S): Hospitalization with observation, expecting spontaneous
      expulsion of the nonviable cervical pregnancy. MAIN OUTCOME MEASURE(S):
      Intrauterine pregnancy preservation; maternal morbidity and mortality. RESULT(S):
      Three weeks after diagnosis, the expulsion of a nonviable cervical pregnancy
      occurred. It was accompanied by pronounced cervical hemorrhage, conservatively
      managed with cervical curettage and stitches under general anesthesia.
      Unfortunately, a few hours later, spontaneous abortion of the intrauterine
      pregnancy occurred. Blood transfusion was postoperatively avoided, although
      pronounced anemia was detected (7.3 g/dL). The patient was than discharged 3 days
      later. CONCLUSION(S): Combined intrauterine and cervical pregnancy is a remote
      but possible event, particularly after assisted reproductive technology (ART)
      procedures. Its management should be carefully evaluated, according to the
      clinical situation and patient's desire. In case of nonviable cervical pregnancy,
      if a noninterventional approach is chosen, and especially when gestational age is
      advanced, hospitalization should be recommended in an attempt to prevent possible
      critical hemorrhagic complications due to cervical pregnancy expulsion.

PMID- 17561009
TI  - Effects on serum lipid and leptin levels of three different doses of
      norethisterone continuously combined with a fixed dose of 17beta-estradiol for
      nasal administration in postmenopausal women: a controlled, double-blind study.
AB  - OBJECTIVE: To evaluate the effect of intranasal continuous combined hormone
      therapy on serum lipids and leptin levels in healthy postmenopausal women.
      DESIGN: Multicenter, double-blind, double-dummy, randomized, controlled study
      conducted in parallel groups. SETTING: Outpatient clinics of three Spanish
      hospitals and two private health centers. PATIENT(S): A total of 333 healthy
      postmenopausal women aged 40 to 75 years. INTERVENTION(S): Women were randomly
      allocated to either one of three different doses of norethisterone (50
      microg/day, 175 microg/day, or 550 microg/day) continuously combined with a fixed
      dose of 17beta-estradiol (350 microg/day) for nasal administration, or 17beta
      estradiol at 2 mg/day combined with oral norethisterone acetate at 1 mg/day. MAIN
      OUTCOME MEASURE(S): Serum lipid, glucose, and leptin levels were assessed at
      baseline and after 12, 24, 36, and 52 weeks of treatment. RESULT(S): Overweight
      women (body mass index >25 kg/m(2)) had higher baseline leptin levels, but these
      levels increased in all groups across the study unrelated to body mass index.
      Both intranasal and oral therapy had the effect of increasing the levels of
      leptin after 24 weeks in healthy postmenopausal women. As expected, total
      cholesterol and low-density lipoprotein cholesterol levels decreased and high
      density lipoprotein levels increased in the four groups. CONCLUSION(S): Body mass
      index is a strong determinant of serum leptin levels in healthy postmenopausal
      women; serum leptin increased in all the hormone therapy regimes.

PMID- 17561010
TI  - Effect of highly purified human chorionic gonadotropin preparations on the gene
      expression signature of stromal cells derived from endometriotic lesions:
      potential mechanisms for the therapeutic effect of human chorionic gonadotropin
      in vivo.
AB  - OBJECTIVE: To investigate alterations in the overall gene expression profile of
      endometriosis-derived stroma with increasing concentrations of hCG by using the
      Affymetrix GeneChip U133 Set. DESIGN: In vitro study. SETTING: Academic research
      institution. PATIENT(S): Women undergoing diagnostic laparoscopic surgery for
      endometriosis. INTERVENTION(S): Increasing concentrations of hCG, added to
      fibroblast monocultures from endometriotic lesions. RESULT(S): We have found that
      hCG concentrations of 0.1 U/mL and higher lead to a dose-dependent increase in
      the expression of 68 genes. Most of the up-regulated genes encoded proteins that
      are involved in cell adhesion, intercellular communication, extracellular matrix
      (ECM) remodeling, apoptosis, and inflammation. We then incubated stromal
      monocultures from nine patients treated with and without 50 U/mL of hCG and
      performed reverse transcriptase-polymerase chain reaction (RT-PCR) for selected,
      highly up-regulated genes to validate our DNA array findings and to confirm that
      the alterations in the gene expression signature are exemplary of patients with
      endometriosis. CONCLUSION(S): We have shown that hCG induces dose-dependent
      alterations in the gene expression profile of stromal cells obtained from
      endometriotic lesions and have, for the first time, identified potential
      mechanisms by which hCG might exert its therapeutic effect on endometriotic
      lesions.

PMID- 17561011
TI  - From black boxes to screening guidelines and antibiotic use: what is it all
      about?

PMID- 17561012
TI  - Erythropoietic-stimulating agents (ESAs): new safety warning.

PMID- 17561013
TI  - Free money (or at least the government's version of "free money").

PMID- 17561014
TI  - Assisted living nursing practice: medication management: part 2 supervision and
      monitoring of medication administration by unlicensed assistive personnel.
AB  - More than half the states permit assistance with or administration of medications
      by unlicensed assistive personnel or med techs. Authorization of this nursing
      activity (or task) is more likely because of state assisted living regulation
      than by support and approval of the state Board of Nursing. In many states, the
      definition of "assistance with" reads exactly like "administration of" thereby
      raising concern with regard to delegation, accountability, and liability for
      practice. It is, as well, a hazardous path for the assisted living nurse who must
      monitor and evaluate the performance of the individual performing this nursing
      task. This article, the second in a series on medication management, addresses
      delegation, standards of practice of medication administration, types of
      medication errors, the components of a performance evaluation tool, and a culture
      of safety. Maintaining professional standards of assisted living nursing practice
      courses throughout the suggested recommendations.

PMID- 17561015
TI  - Identification, optimal management, and infection control measures for
      Clostridium difficile-associated disease in long-term care.
AB  - Residents of long-term care facilities are at an increased risk of exposure to
      Clostridium difficile and become more susceptible to infection after receiving
      antimicrobial therapy. An increasing number and more severe cases of C. difficile
      associated disease (CDAD) have been reported over the last few years and have
      been linked to the emergence of a new, more virulent strain of C. difficile.
      These serious cases of disease have also been associated with a more atypical
      clinical presentation and have prompted the need for an improved means of early
      recognition and identification performed by the nursing staff. This article
      reviews the pathogenesis and risk factors for CDAD, changing epidemiology of
      CDAD, and characteristics of the newly identified strain. Also reviewed are the
      role of nursing in the identification of patients with CDAD; optimal management
      of CDAD; infection control strategies; and education of health care
      professionals, residents, and visitors in the long-term care setting.

PMID- 17561016
TI  - Perceptions of job satisfaction and the regulatory environment among nurse aides
      and charge nurses in long-term care.
AB  - OBJECTIVE: To explore perceptions about job satisfaction and the regulatory
      environment among certified nurse aides (CNAs) and licensed vocational nurses
      (LVNs) in selected nursing homes in West Texas. BACKGROUND: As long-term care
      nurse leaders struggle with maintaining an adequate, well-trained workforce,
      clarifying factors that affect job satisfaction and turnover is essential.
      Studies have identified several factors that contribute to job dissatisfaction
      and turnover, but the extent to which the regulatory environment contributes is
      unknown. METHODS: The study used a qualitative research design with one-on-one
      semistructured interviews conducted with 38 participants employed as CNAs or LVNs
      in 1 of 5 nursing homes located in West Texas. RESULTS: Participants acknowledged
      that regulations pervade their daily work and accept regulatory oversight as
      necessary for providing good care. However, participants expressed concern that
      the presence of the surveyors in the facility often created a tense, almost
      adversarial atmosphere. Other reasons for job dissatisfaction included excessive
      paperwork, ineffective communication, frequent deaths, combative and
      uncooperative residents, and inadequate staffing. CONCLUSIONS: Strategies are
      suggested to improve the survey process, address care-related stressors, promote
      positive communication techniques, reduce paperwork inefficiencies, and reduce
      staff shortages.

PMID- 17561017
TI  - Patterns of and reasons for relocation in dementia care.
AB  - Because dementia is a progressive disease, the need for care in municipal shelter
      accommodations might change over time, raising the crucial question whether to
      relocate an individual. The aim of the study was to investigate the number of
      relocations between municipal dementia housing units and to examine the patterns
      and reasons for relocation, together with the various municipal prerequisites for
      carrying out relocation. Thirty-three managers of 101 dementia care units in 12
      municipalities in Sweden were interviewed, and records of persons who had moved
      into or out of the dementia care units during the year 2002 were reviewed
      retrospectively. The results showed that turnover occurred in 35% of the 865
      rooms during the year. Of those relocations, 78 (9%) were persons who moved to
      another accommodation-either into (59), between (13), or out of (6) a dementia
      care unit. This finding indicates that there are situations in which remaining in
      place was considered less appropriate than relocating a single individual with
      dementia to other accommodations with or without dementia specialization. The
      most common reason for relocation within the municipal shelters was an increased
      need for care.

PMID- 17561018
TI  - The intestinal guanylin system and seawater adaptation in eels.
AB  - Guanylin and uroguanylin are principal intestinal hormones secreted into the
      lumen to regulate ion and water absorption via a specific receptor, guanylyl
      cyclase-C (GC-C). As the intestine is an essential organ for seawater (SW)
      adaptation in teleost fishes, the intestinal guanylin system may play a critical
      role in SW adaptation. Molecular biological studies identified multiple guanylins
      (guanylin, uroguanylin and renoguanylin) and their receptors (GC-C1 and GC-C2) in
      eels. The relative potency of the three ligands on cGMP production in transiently
      expressed receptors was uroguanylin > guanylin >or= renoguanylin for CG-C1 and
      guanylin >or= renoguanylin > uroguanylin for GC-C2. Eel guanylin and GC-C genes
      are expressed exclusively in the intestine and kidney, and the level of
      expression is greater in SW eels than in freshwater (FW) eels except for
      renoguanylin. Physiological studies using Ussing chambers showed that the middle
      and posterior intestine are major sites of action of guanylins, where they act on
      the mucosal side to decrease short circuit current (I(sc)) in a dose-dependent
      manner. The ID(50) of guanylins for transport inhibition was 50-fold greater than
      that of atrial natriuretic peptide that acts from the serosal side as an
      endocrine hormone. However, only guanylins reversed I(sc) to levels below zero.
      Pharmacological analyses using various blockers showed that among transporters
      and channels localized on the intestinal cells of SW teleost fish, the cystic
      fibrosis transmembrane conductance regulator Cl(-) channel (CFTR) on the apical
      membrane is the major target of guanylins. Collectively, guanylins are
      synthesized locally in the intestine and secreted into the lumen to act on the GC
      Cs in the apical membrane of eel intestinal cells. Then, intracellular cGMP
      production after ligand-receptor interaction activates CFTR and probably induces
      Cl(-) and/or HCO3- secretion into the lumen as suggested in mammals. The
      physiological significance of the anion secretion induced by the luminal
      guanylin/GC-C system on SW adaptation may rival or exceed that of the serosally
      derived natriuretic peptides in the euryhaline eel.

PMID- 17561019
TI  - Immunolocalization of 3beta-HSD and 17beta-HSD in the testis of the spotted ray
      Torpedo marmorata.
AB  - Using polyclonal antibodies, we examined the localization of 3beta-hydroxysteroid
      dehydrogenase (3beta-HSD) and 17beta-hydroxysteroid dehydrogenase (17beta-HSD) as
      markers of the site of steroidogenetic activity during the spermatogenesis of
      Torpedo marmorata. These enzymes play a central role in the biosynthesis of
      steroid hormones, including androgen and oestrogen production. We demonstrated
      that in the spotted ray testis, Sertoli and Leydig cells, as well as
      spermatogonia, show a positive reaction to anti 3beta-HSD and 17beta-HSD
      antibodies. In particular, we demonstrated that Sertoli cells show a positive
      reaction to anti 3beta-HSD and 17beta-HSD antibodies in cysts containing
      spermatogonia and spermatozoa, while Leydig cells present a positive reaction
      only when they are located between cysts containing meiotic cells. This study
      strongly suggests that, as hypothesised in our previous study [Prisco, M.,
      Liguoro, A., D'Onghia, B., Ricchiari, L., Andreuccetti, P., Angelini, F., 2002.
      Fine structure of Leydig and Sertoli cells in the testis of immature and mature
      spotted ray Torpedo marmorata. Mol. Reprod. Dev. 63, 192-201.], Sertoli and
      Leydig cells are differently involved in the hormonal control of spermatogenesis:
      Sertoli cells before the beginning of meiosis and after spermiation, Leydig cells
      only during meiosis phase. Moreover, the present paper deals with the possibility
      that also spermatogonia are engaged in the production of androgen hormones, as
      they are characterized by the presence of 3beta-HSD and 17beta-HSD enzymes, and
      show the ultrastructural features of steroid hormone-producing cells.

PMID- 17561020
TI  - Management of periprosthetic femur fractures with a first generation locking
      plate.
AB  - Periprosthetic femoral fractures associated with well-fixed total hip or total
      knee prostheses present a challenging management problem as these injuries
      typically occur in osteoporotic bone. Conventional management entails extensive
      periosteal stripping to allow for plate fixation. We reviewed a consecutive
      series of patients who sustained fractures associated with a well fixed total
      knee prosthesis, a total hip prosthesis, or both. Twenty four patients with a
      mean age of 69.4 years were included. All patients underwent fixation via
      percutaneous insertion techniques with a first generation locking plate and
      screws (LISS--Less Invasive Skeletal Stabilization, Synthes, Paoli, PA). Three
      patients sustained fractures distal to a well-fixed total hip prosthesis,
      eighteen fractures occurred above a well-fixed total knee femoral component, and
      three were interprosthetic. The mean length of time from the index procedure to
      fracture was 76 months, range (2-172 months). Blood loss was minimal in each
      case, with a mean operative time of 90 min (range 60-120 min). Twenty one of
      twenty four went on to unite at a mean 6.2 months (range 3-19 months). Three
      patients underwent further surgery. One failure of fixation was encountered.
      Percutaneous fixation is technically demanding as it requires stable fixation
      without direct visualisation of the fracture site or the entire fixation device.
      Our results suggest percutaneous fixation with the LISS plate is an effective
      although technically demanding method of treatment. Complication rates were
      comparable to existing reports of this treatment method, and appear to be
      improved over traditional methods of fixation.

PMID- 17561021
TI  - Identification of immuno-reactive proteins from a sheep gastrointestinal
      nematode, Trichostrongylus colubriformis, using two-dimensional electrophoresis
      and mass spectrometry.
AB  - Gastrointestinal nematode infections of livestock animals are prevalent and
      costly problems worldwide. Currently, infections are controlled by anthelmintic
      chemicals but increasing drug resistance has prompted research interest to shift
      towards alternative methods of control such as vaccine development and selection
      of worm-resistant animals. The present study analyses proteins from
      Trichostrongylus colubriformis infective L3s that are recognised by IgG of immune
      sheep. Following protein separation via two-dimensional electrophoresis and
      Western blot probing with plasma from sheep resistant to T. colubriformis, mass
      spectrometry-based proteomic analyses were used to identify immuno-reactive
      protein spots. We were able to identify 28 immune targets, including aspartyl
      protease inhibitor, enolase, chaperone proteins, galectin, glycolytic enzymes,
      kinase, phosphatase and structural muscle proteins such as myosin, paramyosin,
      calponin and DIM-1. The data suggest that immune responses to T. colubriformis
      are dispersed over a relatively large number of parasite antigens, including
      several cytoplasmically expressed proteins. The results have new implications for
      understanding the molecular mechanisms that underpin host-parasite interaction
      during gastrointestinal nematode infections.

PMID- 17561022
TI  - Neoparamoeba perurans n. sp., an agent of amoebic gill disease of Atlantic salmon
      (Salmo salar).
AB  - Amoebic gill disease (AGD) is a potentially fatal disease of some marine fish.
      Two amphizoic amoebae Neoparamoeba pemaquidensis and Neoparamoeba branchiphila
      have been cultured from AGD-affected fish, yet it is not known if one or both are
      aetiological agents. Here, we PCR amplified the 18S rRNA gene of non-cultured,
      gill-derived (NCGD) amoebae from AGD-affected Atlantic salmon (Salmo salar) using
      N. pemaquidensis and N. branchiphila-specific oligonucleotides. Variability in
      PCR amplification led to comparisons of 18S rRNA and 28S rRNA gene sequences from
      NCGD and clonal cultured, gill-derived (CCGD) N. pemaquidensis and N.
      branchiphila. Phylogenetic analyses inferred from either 18S or 28S rRNA gene
      sequences unambiguously segregated a lineage consisting of NCGD amoebae from
      other members of the genus Neoparamoeba. Species-specific oligonucleotide probes
      that hybridise 18S rRNA were designed, validated and used to probe gill tissue
      from AGD-affected Atlantic salmon. The NCGD amoebae-specific probe bound AGD
      associated amoebae while neither N. pemaquidensis nor N. branchiphila were
      associated with AGD-lesions. Together, these data indicate that NCGD amoebae are
      a new species, designated Neoparamoeba perurans n.sp. and this is the predominant
      aetiological agent of AGD of Atlantic salmon cultured in Tasmania, Australia.

PMID- 17561023
TI  - The impact of parasites on the life history evolution of guppies (Poecilia
      reticulata): the effects of host size on parasite virulence.
AB  - There is large spatial and temporal variation in the Gyrodactylus parasite fauna
      across natural guppy (Poecilia reticulata) populations in Trinidad. The life
      history evolution of these fish could be affected differently in the various
      habitats depending on the local parasite selection pressure. Here, we
      experimentally infected three guppy populations with three gyrodactylid strains
      in the laboratory and monitored the infection by recording the number of
      parasites and host mortality in a full factorial design. The origin of the guppy
      population and parasite strain, and the size of the hosts explained significant
      variation in the survival of hosts. Larger fish carried the highest parasite
      loads and experienced the highest mortality rates, which suggests that parasite
      mediated selection may favour smaller phenotypes, possibly counter-balancing
      selection pressures by gape-limited predators, mate choice and female fecundity.
      We observed significant variation in virulence between parasite strains with the
      captive-bred experimental strain (Gt3) causing the highest mortality of hosts
      whilst reaching only relatively low maximum burdens. This suggests that
      adaptations to the captive environment and/or inbreeding depression may alter the
      virulence of such captive-bred parasites. There were significant differences in
      survival rate between guppy populations, with infected guppies from the large
      population of the Lower Aripo River showing a higher survival rate than the fish
      from the small and genetically less diverse Upper Aripo River population.

PMID- 17561024
TI  - Endothelial cell response to biomechanical forces under simulated vascular
      loading conditions.
AB  - In vivo, endothelial cells (EC) are constantly exposed to the haemodynamic forces
      (HF) of pressure, wall shear stress and hoop stress. The main aim of this study
      was to design, create and validate a novel perfusion bioreactor capable of
      delivering shear stress and intravascular pressure to EC in vitro and to
      characterise their morphology, orientation and gene expression. Here we report
      the creation and validation of such a simulator and the dual application of
      pressure (120/60 mmHg) and low shear stress (5 dyn/cm(2)) to a monolayer of EC
      established on a non-compliant silicone tube. Under these conditions, EC
      elongated and realigned obliquely to the direction of applied shear stress in a
      time-dependent manner. Furthermore, randomly distributed F-actin microfilaments
      reorganised into long, dense stress fibres crossing the cells in a direction
      perpendicular to that of flow. Finally, combinatorial biomechanical conditioning
      of EC induced the expression of the inflammatory-associated E-selectin gene.

PMID- 17561025
TI  - Novel combined stir bar sorptive extraction coupled with ultrasonic assisted
      extraction for the determination of brominated flame retardants in environmental
      samples using high performance liquid chromatography.
AB  - A combined stir bar coated with poly (dimethysiloxane)-beta-cyclodextrin (PDMS
      beta-CD) on single side has been prepared for the first time by sol-gel method
      and was coupled with ultrasonic assisted extraction (UAE) for the determination
      of some brominated flame-retardant compounds (BFRs) in soil and dust samples by
      high performance liquid chromatography (HPLC). Four different kinds of coatings
      including PDMS-beta-CD, PDMS, carbowax (CW)-PDMS-poly (vinyl alcohol) (PVA) and
      PDMS-PVA were evaluated for stir bar sorptive extraction of BFRs by orthogonal
      experiment design. The experimental results reveal that the PDMS-beta-CD combined
      stir bar exhibited the best extraction efficiency for the target analytes. The
      reproducibility for the preparation of PDMS-beta-CD combined stir bar ranged from
      1.3% to 15.7% in one batch, and 7.2% to 15.1% among batches. Extraction time,
      desorption solvent, concentration of methanol and NaCl in the matrix, pH,
      temperature and stirring speed were optimized. The combined stir bar can avoid
      direct friction of the coating with the bottom of the vessel, and could be used
      for more than 100 times. Linearity (>0.993), repeatability (<10.5%),
      reproducibility (<16.5%), recovery (56-118%) and detection limits (2.9-4.2 microg
      L(-1)) were proper to determine the seven BFRs. The developed method was applied
      to the determination of BFRs in soil and dust with satisfactory results.

PMID- 17561026
TI  - Membrane microfilter device for selective capture, electrolysis and genomic
      analysis of human circulating tumor cells.
AB  - This paper presents development of a parylene membrane microfilter device for
      single stage capture and electrolysis of circulating tumor cells (CTCs) in human
      blood, and the potential of this device to allow genomic analysis. The presence
      and number of CTCs in blood has recently been demonstrated to provide significant
      prognostic information for patients with metastatic breast cancer. While finding
      as few as five CTCs in about 7.5mL of blood (i.e., 10(10) blood cells in) is
      clinically significant, detection of CTCs is currently difficult and time
      consuming. CTC enrichment is performed by either gradient centrifugation of CTC
      based on their buoyant density or magnetic separation of epithelial CTC, both of
      which are laborious procedures with variable efficiency, and CTC identification
      is typically done by trained pathologists through visual observation of stained
      cytokeratin-positive epithelial CTC. These processes may take hours, if not days.
      Work presented here provides a micro-electro-mechanical system (MEMS)-based
      option to make this process simpler, faster, better and cheaper. We exploited the
      size difference between CTCs and human blood cells to achieve the CTC capture on
      filter with approximately 90% recovery within 10 min, which is superior to
      current approaches. Following capture, we facilitated polymerase chain reaction
      (PCR)-based genomic analysis by performing on-membrane electrolysis with embedded
      electrodes reaching each of the individual 16,000 filtering pores. The biggest
      advantage for this on-membrane in situ cell lysis is the high efficiency since
      cells are immobilized, allowing their direct contact with electrodes. As a proof
      of-principle, we show beta actin gene PCR, the same technology can be easily
      extended to real time PCR for CTC-specific transcript to allow molecular
      identification of CTC and their further characterization.

PMID- 17561027
TI  - Capillary high-performance liquid chromatography with mass spectrometry for
      simultaneous determination of major flavonoids, iridoid glucosides and saponins
      in Flos Lonicerae.
AB  - Flos Lonicerae, a traditional herbal medicine, has been used in China to treat
      some inflammatory disease. Several different classes of compounds have been
      separated from the herb to assess their pharmacological activities. Among these
      classes, flavonoids, iridoid glycosides and saponins have been well studied and
      may be responsible for its clinical application. Therefore, quality control of
      Flos Lonicerae is an important issue for drug safety and validity evaluations. A
      quantitative method consisting of solid phase extraction followed by capillary
      high-performance liquid chromatography-diode array detection/electrospray
      ionization mass spectrometry (capillary HPLC-DAD/ESI-MS) was developed for
      simultaneously assay of 24 compounds in Flos Lonicerae. Under optimized capillary
      HPLC-DAD/ESI-MS conditions, these compounds, including nine flavonoids, eight
      iridoid glucosides and seven saponins, were separated with high efficiency in the
      selected-ion monitoring (SIM) mode. Linearity of the method was good with
      correlation coefficients (r(2)) in the range of 0.9935-0.9998 and detection
      limits were lower than 2.57 ng/mL for most of analytes. The obtained recoveries
      varied between 91.0 and 108.7% with the relative standard deviations (RSDs)
      within 8.74% (n=3). The capillary HPLC-DAD/ESI-MS method was also successfully
      applied to the analysis of these compounds in five species of Flos Lonicerae. It
      was demonstrated to be a powerful tool for comprehensive analysis of herbal
      medicines, owing to its exclusive selectivity and excellent sensitivity.

PMID- 17561029
TI  - Befriend your oral and maxillofacial radiologist.

PMID- 17561030
TI  - Guidelines have been written, should be updated.

PMID- 17561031
TI  - Treatment guidelines.

PMID- 17561032
TI  - Friction might increase anchorage loading.

PMID- 17561035
TI  - Curve of Spee.

PMID- 17561036
TI  - Many hurdles to academic career.

PMID- 17561037
TI  - Where have all the jobs gone?

PMID- 17561039
TI  - So, those who can't do it, teach it?

PMID- 17561038
TI  - Show us the money!

PMID- 17561040
TI  - Kesling archwire slot.

PMID- 17561041
TI  - Histomorphologic and histomophometric evaluation of immediately and early loaded
      mini-implants for orthodontic anchorage.
AB  - INTRODUCTION: The purpose of this study was to evaluate the bone response to
      statically loaded 2.5-mm diameter mini-implants of 6 and 10 mm lengths activated
      after various healing periods in a dog model. METHODS: Seventy-eight machined
      surface Ti-6Al-4V mini-implants were bilaterally placed in the mandibular
      premolar and molar regions of 6 beagle dogs. The left (experimental) and the
      right (control) hemi-arches received 6 and 7 mini-implants, respectively.
      Experimental mini-implants healing periods of 0 days (immediately activated), 1
      week, and 3 weeks were followed by a 12-week load activation period (250 g
      between parallel implant pairs). Control (nonloaded) mini-implant groups were
      placed for 12 weeks, 3 weeks, and 1 week before the dogs were killed they
      provided data concerning the experimental groups' bone to mini-implant scenarios
      at load activation times. The mandibles were exposed by sharp dissection, and
      decalcified specimens were prepared for histomorphologic and histomorphometric
      (bone to mini-implant contact) assessment. RESULTS: Survival rates were 100% and
      77.78% for the control and the experimental groups, respectively. Survival rates
      were 88.89% for the 10-mm and 66.67% for the 6-mm experimental groups. All failed
      devices had tissue inflammation and were lost after spring placement. The control
      groups showed classic bone-healing events, and the experimental groups showed
      mature bone morphology after 12 weeks in vivo regardless of placement time before
      load activation. Bone to implant contact values were not significantly different
      between the experimental and the control groups that remained 12 weeks in vivo.
      CONCLUSIONS: These results showed that low-intensity immediate or early
      orthodontic static loads did not affect mini-implant performance.

PMID- 17561042
TI  - In-vitro evaluation of frictional resistance between brackets with passive
      ligation designs.
AB  - INTRODUCTION: The lower frictional resistance produced by passive self-ligating
      brackets can be helpful during orthodontic sliding mechanics. The aims of this
      study were to evaluate the frictional resistance of brackets with passive
      ligation and to compare these values with corresponding controls. METHODS: Two
      passive self-ligating brackets (Damon SL II, Sybron Dental Specialties/Ormco,
      Orange, Calif; SmartClip, 3M Unitek, Monrovia, Calif) and 1 novel bracket with
      passive elastic ligation (Synergy, Rocky Mountain Orthodontics, Denver, Colo)
      were used. The brackets were coupled with 3 nickel-titanium archwires (0.014-in
      round, 0.016 x 0.022-in, 0.019 x 0.025-in) in a simulated ideal arch introducing
      first-order rotations of 3 degrees and 6 degrees, second-order intrusions of 0.5
      and 1.0 mm, and a third-order labial crown inclination of 3 degrees . The
      dimensions of the brackets were measured with scanning electron micrographs. The
      results of initial maximum drawing forces (IMDF) were analyzed by 2-way ANOVA and
      1-way ANOVA tests. RESULTS: The SmartClip bracket had larger critical angles and
      distances for binding than the other 2 brackets. When coupled with 0.019 x 0.025
      in archwires in an ideal arch alignment, SmartClip brackets had lower IMDF than
      the other brackets. For the first-order rotations, Synergy brackets had
      significantly lower IMDF than the other brackets. Damon SL II brackets with
      smaller critical angles had greater IMDF. For the third-order inclination, the
      Damon SL II brackets with less torsional play also had greater IMDF. No
      significant differences of IMDF were found for all the brackets tested in second
      order intrusions. However, IMDF increased as the severity of the malocclusion
      increased. CONCLUSIONS: No significant bracket differences were found when
      binding occurred in second-order distances. In an ideal arch alignment, brackets
      with greater slot lumen have lower frictional resistance. First-order rotational
      control was influenced by slot depth, bracket width, and labial cover of the
      brackets with the same archwire. When a sliding mechanism was used with a third
      order inclination change, the brackets with smaller third-order critical contact
      angles had greater frictional resistance.

PMID- 17561043
TI  - Prevention of demineralization around orthodontic brackets in vitro.
AB  - INTRODUCTION: The demineralization of enamel adjacent to orthodontic brackets is
      a significant clinical problem. The purpose of this in-vitro study was to
      investigate the effect of sodium fluoride (Colgate Neutrafluor 9000 ppm) (NaF)
      and 10% casein phosphopeptide-amorphous calcium phosphate (GC Tooth Mousse) (TM)
      on enamel demineralization adjacent to orthodontic brackets. METHODS: Forty
      specimens were sectioned from the buccal or lingual surfaces of extracted sound
      third molars. Twenty specimens had molar tubes bonded with composite resin
      (Transbond XT, 3M, St Paul, Minn) (CR), and 20 were bonded with resin-modified
      glass ionomer cement (Fuji Ortho LC, GC America, Alsip, Ill) (RMGIC). A 2-mm
      window for enamel demineralization was prepared. The specimens were randomly
      divided into 4 treatment groups: control, TM, TM/NaF (50/50 w/w), and NaF. The
      treatment solutions were placed around the bracket margins, and the specimens
      were immersed inverted into a carbopol demineralization solution at 37 degrees C.
      The enamel specimens were exposed for 96 hours, with the demineralization and
      topical solutions changed every 4 hours. Quantitative light-induced fluorescence
      (QLF) images were taken every 8 hours under controlled conditions. The difference
      in fluorescence (DeltaF) and the proportional DeltaF (%F) change between baseline
      and 96 hours was calculated. RESULTS: RMGIC significantly reduced DeltaF and %F
      when compared with CR (ANOVA, P = .029 and P = .034, respectively). Application
      of TM with CR, NaF with CR, and TM/NaF with CR significantly reduced DeltaF and
      %F compared with the control CR (Tukey post-hoc test, P <.001). Application of
      TM/NaF with RMGIC significantly reduced DeltaF and %F compared with the control
      RMGIC (Tukey post-hoc test, P = .008, P = .019, respectively). CONCLUSIONS: With
      the limitations of any in-vitro study, the following clinical conclusions can be
      drawn. The use of RMGIC alone can significantly decrease enamel demineralization
      compared with CR. The application of TM/NaF can provide significant additional
      prevention of enamel demineralization when RMGIC is used for bonding. The
      application of TM, NaF, or TM/NaF can significantly prevent enamel
      demineralization when CR is used for bonding. The use of both agents should be
      recommended for any at-risk orthodontic patient to provide preventive actions and
      potentially remineralize early (subclinical) enamel demineralization.

PMID- 17561044
TI  - In-vivo evaluation of the bacterial contamination and disinfection of acrylic
      baseplates of removable orthodontic appliances.
AB  - INTRODUCTION: This randomized clinical trial assessed, by using microbial culture
      and scanning electron microscopy (SEM), the contamination by mutans streptococci
      (MS) colonies/biofilms on acrylic baseplates of removable orthodontic appliances
      and evaluated the efficacy of antimicrobial sprays (Periogard [Colgate-Palmolive
      Ind. Brasileira, Osasco, SP, Brazil], Cepacol [Merrell Lepetit Farmaceutica e
      Industrial Ltda, Santo Amaro, SP, Brazil], and sterile tap water [control]) on
      their disinfection. METHODS: Seventeen children were randomly enrolled in a 3
      stage changeover system with a 1-week interval between each stage. All solutions
      were used in all stages by a different group of children. The acrylic baseplates
      were worn full time except at meals. At the end of each week of the trial, the
      baseplates were submitted to a randomized disinfection protocol and were sent for
      microbiologic analysis. New baseplates were constructed, and the same sequence of
      procedures was repeated 2 more times. Acrylic baseplates representing each test
      solution were examined by SEM. The Friedman test assessed differences at the 5%
      significance level among the solutions for MS biofilm formation on acrylic
      surface. RESULTS: Cepacol and Periogard reduced the formation of MS
      colonies/biofilms, and both solutions differed statistically from sterile tap
      water (P <.001). However, Periogard was significantly more effective against MS
      than Cepacol (P <.001). When MS colonies/biofilms were detected on acrylic
      surfaces under stereomicroscopy, this was confirmed with SEM. CONCLUSIONS:
      Acrylic baseplates of removable orthodontic appliances worn by children were
      contaminated by MS colonies/biofilms in all cases after 1 week. Although Cepacol
      had better results than sterile tap water, spraying with Periogard showed
      significantly greater efficacy in reducing MS colonies/biofilms on acrylic
      surfaces.

PMID- 17561045
TI  - Facial height comparison in young white and black Brazilian subjects with normal
      occlusion.
AB  - INTRODUCTION: In this study, we aimed to cephalometrically compare anterior and
      posterior facial heights in young white and black Brazilian subjects with normal
      occlusion and to verify sexual dimorphism. METHODS: The sample comprised the
      lateral cephalograms of untreated normal Brazilians, divided into 2 groups. Group
      1 included 74 white subjects (37 of each sex), with a mean age of 13.71 years (SD
      0.84); group 2 included 56 black subjects (28 of each sex), with a mean age of
      13.86 years (SD 0.92). The variables studied were obtained from various
      cephalometric analyses. Sexual dimorphism was investigated in the groups.
      Independent t tests were used for intergroup comparisons. RESULTS: The white
      subjects had significantly greater upper anterior facial height (UAFH) and
      proportion of UAFH to total anterior facial height (TAFH), and significantly
      smaller proportion of lower anterior facial height (LAFH) to TAFH than the black
      subjects. Black boys had significantly greater total posterior face height (TPFH)
      and UAFH and upper posterior face height (UPFH) and UPFH/TPFH proportion than
      black girls. Black girls had significantly greater LPFH/TPFH proportion than
      boys. White boys had significantly greater UPFH and UPFH/TPFH proportion than
      white girls. White girls had significantly greater LPFH/TPFH and facial height
      index values than boys. CONCLUSIONS: White subjects had larger UAFH, whereas
      black subjects had proportionally larger LAFH. Boys have a greater tendency for a
      vertical pattern than girls.

PMID- 17561046
TI  - Can we extract useful and scientifically sound information from retrospective
      nonrandomized trials to be applied in orthodontic evidence-based practice
      treatments?

PMID- 17561048
TI  - Are malocclusions more prevalent and severe now? A comparative study of medieval
      skulls from Norway.
AB  - INTRODUCTION: The prevalence of malocclusion in modern populations is higher than
      in excavated samples from ancient times. Presently, more than 30% of children and
      adolescents in the Scandinavian countries receive orthodontic treatment. The aims
      of this study were to describe the prevalence and severity of malocclusions in a
      sample of medieval Norwegians, to evaluate the need for treatment by using the
      Norwegian need for orthodontic treatment index (NOTI), and to compare these
      findings with a modern sample already analyzed with the same index. METHODS: The
      material consisted of 85 male and 61 female medieval skulls from abandoned and
      later excavated graveyards of 16th century Oslo that were evaluated with the
      NOTI. RESULTS: Only 36% of the medieval group showed objective assessed needs for
      orthodontic treatment, compared with 65% of the present-day sample. Among the
      skulls, the objective needs for treatment were 27% for the males and 49% for the
      females. No sex differences related to severity or prevalence of malocclusion
      were found in the modern sample. The medieval sample arranged according to
      severity was great need (B), 7%; obvious need (C), 29%; and little/no need (D/E),
      64%. The findings in the modern sample were B, 20%; C, 44%; and D/E, 35%. The
      female skulls showed greater severity and prevalence than the male skulls. No
      skull had very great need (A). CONCLUSIONS: This study indicates a significant
      increase in both the prevalence and the severity of malocclusions during the last
      400 to 700 years in Oslo, Norway. Furthermore, although no sex differences were
      found in the modern sample, females had both a higher prevalence of malocclusions
      and more severe malocclusions than did males in the past.

PMID- 17561049
TI  - Treatment stability with the eruption guidance appliance.
AB  - INTRODUCTION: Although the eruption guidance appliance has been used to correct
      Class II malocclusions for many years and its effects have been demonstrated,
      there is no study on the stability of the changes it produces. Therefore, the
      objective of this study was to investigate the long-term stability of
      cephalometric dentoskeletal and occlusal changes after eruption guidance
      appliance therapy. METHODS: Thirty-nine patients were evaluated. Occlusal
      evaluations were made with the peer asseessment rating index, and anterior tooth
      irregularity was evaluated with the Little irregularity index. Cephalometric and
      occlusal data were obtained at pretreatment, posttreatment, and postretention.
      The data were analyzed by dependent 1-way analysis of variance (ANOVA) for
      comparison between the 3 stages of the experimental group, with the Newman-Keuls
      test as a second step. To compare the cephalometric experimental group changes
      with mean population changes, the t test was used. RESULTS: Cephalometrically, in
      the postretention stage, overjet remained stable, overbite showed significant
      relapse, and molar relationship improved toward a Class I relationship. The peer
      asseessment rating index showed stability of the occlusion. The Little
      irregularity index demonstrated a statistically significant relapse of crowding
      in the postretention stage. CONCLUSIONS: Cephalometrically, overjet and molar
      relationship were stable in the long term after treatment with the eruption
      guidance appliance; however, there was relapse of the overbite. Occlusally,
      correction of the malocclusion elevated by the peer assessment rating was stable.
      There was relapse of the anterior teeth crowding.

PMID- 17561050
TI  - Apical root resorption comparison between Frankel and eruption guidance
      appliances.
AB  - INTRODUCTION: The objectives of this study were to compare the amounts of apical
      root resorption that occur after treatment with 2 removable appliances-the
      Frankel function regulator and the eruption guidance appliance (EGA)-in an
      untreated control group, and to determine the prevalence of root resorption in
      the maxillary and mandibular incisors and the dental arches. METHODS: After
      treatment, periapical radiographs were obtained of the maxillary and mandibular
      incisors with the long-cone paralleling technique from 72 patients divided into 3
      groups. Group 1 included 24 patients treated with the Frankel appliance, group 2
      consisted of 24 patients treated with the EGA, and group 3 comprised 24 untreated
      subjects. Some patients in groups 1 and 2 were also treated with fixed
      appliances. Subgroups of patients who had used exclusively 1 functional appliance
      were also formed and evaluated. Root resorption was scored according to the
      method of Levander and Malmgren. RESULTS: Results of the Kruskal-Wallis tests
      showed significantly greater resorption in the Frankel group, the EGA group, and
      the EGA subgroup in relation to the control group. However, there were no
      statistically significant differences between the Frankel and the EGA groups and
      the subgroups. The amounts of resorption were predominantly small and similar in
      the experimental groups and the subgroups. The prevalence of resorption for the
      incisors was greatest for the maxillary central, followed by the maxillary
      lateral, mandibular central, and mandibular lateral. CONCLUSIONS: It was
      concluded that the Frankel group, the EGA group, and the EGA subgroup had
      significantly greater resorption than the control group. There was no difference
      in the amount of resorption between the Frankel and the EGA groups.

PMID- 17561051
TI  - Prevalence of cariogenic streptococci on incisor brackets detected by polymerase
      chain reaction.
AB  - INTRODUCTION: Streptococcus mutans and Streptococcus sobrinus are the main
      causative organisms for enamel demineralization during orthodontic treatment. In
      this study, we analyzed the prevalence of cariogenic streptococci adhering to
      incisor brackets. METHODS: Four incisor brackets from both the maxilla and the
      mandible were collected from 80 patients at debonding, immediately after the
      visible plaque index and the gingival bleeding index were measured from the
      incisors. The genomic DNA of adhered cariogenic streptococci was extracted and
      amplified by using polymerase chain reaction, and the prevalence of cariogenic
      streptococci was determined and compared with oral hygiene indexes in the incisor
      area. RESULTS: The results showed that the prevalence of S mutans on incisor
      brackets was higher than that of S sobrinus, and the maxillary incisor brackets
      were colonized by both cariogenic streptococci to a somewhat higher degree than
      were the mandibular brackets. The prevalence of S mutans was 50.0% on the
      maxillary incisor brackets and 33.8% on the mandibular incisor brackets, but that
      of S sobrinus was 17.5% and 15.0%, respectively. At least 1 species of cariogenic
      streptococci was detected on the incisor brackets of 51 subjects (63.7%).
      However, the prevalence of cariogenic streptococci was not significantly
      associated with the oral hygiene indexes at debonding. CONCLUSIONS: Cariogenic
      streptococci can adhere to orthodontic brackets. Careful hygiene control around
      orthodontic brackets is important.

PMID- 17561052
TI  - Sagittal and vertical load-deflection and permanent deformation of transpalatal
      arches connected with palatal implants: an in-vitro study.
AB  - INTRODUCTION: The purposes of this laboratory investigation were to (1) measure
      the sagittal and vertical deflection of loaded transpalatal arches (TPAs)
      connected to a palatal implant, (2) measure the extent of permanent deformation
      of the connecting TPA in the sagittal and vertical directions, (3) test various
      wire dimensions in terms of deflection behavior, and (4) evaluate soldering vs
      laser welding vs adhesive bonding of TPAs in terms of load deflection behavior.
      METHODS: Stainless steel wires of 6 dimensions were tested: 0.8 x 0.8, 0.9, 1,
      1.1, 1.2, and 1.2 x 1.2 mm. For each dimension, 10 specimens were soldered to the
      palatal implant abutment, 10 were laser welded, and 10 were adhesively bonded to
      the implant abutment (total, 180 specimens). The measuring device applied
      increments of force of 50 cN, from 0 to 500 cN. Then the specimens were unloaded.
      The values were statistically described and analyzed with ANOVA and Wilcoxon rank
      sum tests. RESULTS AND CONCLUSIONS: Absolute orthodontic anchorage without
      deformation of TPAs was not observed with the wire dimensions tested. To prevent
      loss of anchorage greater than 370 mum (sagittal deflection of 1.2 x 1.2 mm
      adhesively bonded TPA at 500 cN force level), wires thicker than 1.2 x 1.2 mm or
      cast anchorage elements must be considered for clinical practice. However, larger
      cross sections might cause more patient discomfort, and laboratory procedures
      increase costs.

PMID- 17561053
TI  - Bonding properties of newly erupted and mature premolars.
AB  - INTRODUCTION: The purpose of this study was to determine whether there were
      differences in bond strength between mature and newly erupted teeth when using
      both conventional and self-etching primer techniques for bonding orthodontic
      appliances. The nature of adhesive bond failure among the groups was also
      compared by using the adhesive remnant index (ARI). METHODS: Premolars were
      collected, randomly divided, and bonded with either the conventional or the self
      etching technique. Brackets were debonded on a testing machine with a shear
      testing device. Bond strengths were compared with ANOVA and the Weibull analysis.
      RESULTS: There were no statistically significant differences in bond strength
      values between the conventional etching and the self-etching primer groups or
      between newly erupted and mature teeth. ARI scores differed between mature and
      newly erupted teeth. Newly erupted teeth had more adhesive failures, and mature
      teeth had more cohesive bond failures at the enamel-composite resin interface.
      CONCLUSIONS: Based on these results, bond strength does not appear to be affected
      by the posteruptive enamel maturation process.

PMID- 17561054
TI  - Facial soft-tissue analysis of Korean adults with normal occlusion using a 3
      dimensional laser scanner.
AB  - INTRODUCTION: Developments in computer technology have made the 3-dimensional
      (3D) diagnosis of facial soft tissues possible, opening the window for 3D soft
      tissue evaluation in orthodontic treatment planning and posttreatment results.
      METHODS: Korean adults (30 men, 30 women) with normal occlusion were scanned with
      a 3D laser scanner, and 3D facial images were made with the Rapidform 2004
      program (Inus Technology, Seoul, Korea). Reference planes in the facial soft
      tissues of the 3D image were established, and a 3D coordinate system (X-axis,
      left/right; Y-axis, superior/inferior; Z-axis, anterior/posterior) was
      established; 29 measurement points were assigned on the 3D image, and 39 linear
      measurements, 8 angular measurements, and 29 linear distance ratios were
      obtained. RESULTS: Significant differences between the sexes were found in
      nasofrontal angle (men, 142 degrees; women, 147 degrees) and transverse nasal
      prominence (men, 112 degrees; women, 116 degrees) (P <.05). Transverse upper lip
      prominence was 107 degrees in the men and 106 degrees in the women, and
      transverse mandibular prominence was 76 degrees in both sexes. The distance
      between lower lip vermilion border (Li) and Me' was 0.4 times mandibular body
      length (Me' - Go'), and mouth height was also 0.4 times the mouth width. The
      linear distance ratios from the coronal reference plane to fronto-temporal point,
      zygomatic point, pronasale, upper lip point, labrale inferior, and soft-tissue
      menton were -1, -1, 1, 0.5, 0.5, and -0.6, respectively. CONCLUSIONS: These data
      could be guidelines for the 3D evaluation of the facial image, because the 3D
      facial model constructed by the averaged coordinate values could be a template
      for orthodontic diagnosis and treatment planning.

PMID- 17561055
TI  - Ingestion of orthodontic anchorage screws: an experimental study in dogs.
AB  - INTRODUCTION: Sharp-edged foreign bodies that are accidentally swallowed can
      become lodged in the stomach. This animal study was undertaken to determine the
      outcome of orthodontic anchorage screw ingestion. METHODS: We evaluated
      radiographs of 10 mixed-breed dogs that ingested 10 orthodontic anchorage screws
      and 10 reamers (1 screw and 1 reamer per dog). RESULTS: All orthodontic anchorage
      screws and all but 2 reamers were spontaneously passed within 7 days.
      CONCLUSIONS: Further investigation is needed to determine whether the results of
      our animal study agree with clinical findings.

PMID- 17561056
TI  - Diagnostic performance study on the relationship between the exfoliation of the
      deciduous second molars and the pubertal growth spurt.
AB  - INTRODUCTION: The aim of this study was to evaluate the possible relationship
      between the exfoliation of the deciduous second molars (Es) and the onset of the
      pubertal growth spurt assessed with the cervical vertebral maturation method.
      METHODS: The ability to identify the onset of the pubertal growth spurt (cervical
      stage 3, CS3) was evaluated in a sample of 123 patients with exfoliation of the
      Es (exfoliation group) with respect to a control group of 250 subjects in the
      late mixed dentition selected with random criteria. Tests of diagnostic
      performance were applied. RESULTS: The comparison of the prevalence rates of CS3
      in the exfoliation group vs the control group was not statistically significant.
      The positive likelihood ratio was smaller than 1, thus indicating lack of
      diagnostic power of the exfoliation of the deciduous second molars with regard to
      CS3. CONCLUSIONS: No significant relationship was found between the moment of
      exfoliation of the Es and the onset of the pubertal growth spurt.

PMID- 17561057
TI  - Forces released by esthetic preadjusted appliances with low-friction and
      conventional elastomeric ligatures.
AB  - INTRODUCTION: In this in-vitro study, we compared the forces generated by 2 types
      of esthetic brackets (Aqua [Leone Orthodontic Products, Sesto Fiorentino,
      Florence, Italy] and Mystique [GAC International, Bohemia, NY]) in association
      with low-friction ligature systems (Slide [Leone Orthodontic Products] and Neo
      Clips [GAC International], respectively) and by the same brackets combined with
      conventional elastomeric ligatures (CEL) during the leveling and aligning phases.
      METHODS: The testing model consisted of 5 esthetic ceramic 0.022-in preadjusted
      brackets for the second premolar, the first premolar, the canine, the lateral
      incisor, and the central incisor. The canine bracket was bonded to a sliding bar
      that allowed for various vertical positions. The forces generated by a 0.014-in
      superelastic nickel titanium wire, with the 2 types of esthetic low-friction
      systems (Aqua with Slide and Mystique with Neo-Clips) and the same esthetic
      brackets with CEL at various amounts of canine misalignment (1.5, 3, 4.5, and 6
      mm) were recorded. RESULTS AND CONCLUSIONS: A significantly greater amount of
      force was released with low-friction systems when compared with CEL systems for
      all the tested variables (P < .05), with the exception of the 1.5-mm canine
      misalignment, and the 6.0-mm canine misalignment limited to Mystique with Neo
      Clips. Similar forces were released with both esthetic low-friction systems. The
      average amount of released force with CEL was approximately zero at 3.0 mm or
      more of canine misalignment.

PMID- 17561058
TI  - High-resolution multislice computerized tomography with multiplanar and 3
      dimensional reformation imaging in rapid palatal expansion.
AB  - INTRODUCTION: The purpose of this study was to evaluate whether high-resolution
      multislice computerized tomography (CT) with multiplanar reformation and 3
      dimensional (3D) imaging is helpful in demonstrating the effects on midfacial
      sutures induced by rapid palatal expansion (RPE), thereby appraising and
      corroborating the current state of the art or possibly adding new findings.
      METHODS: Two patients in different stages of skeletal maturity (aged 10 and 16
      years) underwent CT examinations immediately after active opening with the RPE
      appliance. RESULTS: The 3D CT imaging method proved to be valuable in visualizing
      skeletal effects on not only the midpalatal suture, but also adjacent sutures. It
      allowed precise 3D location of tooth positions. In the 3D CT images of 1 patient,
      the complete opening of the midpalatal suture was visible. The median dissection
      of the incisal foramen at the point of unification of the 2 nasopalatine channels
      could be visualized. Additionally, the positions of severely displaced maxillary
      canines could be located precisely. In the other patient, apart from the
      completely open midpalatal suture, the opening or widening of the internasal
      suture, the nasomaxillary sutures, and the frontomaxillary sutures were visible.
      CONCLUSIONS: The 3D imaging of high-resolution multislice CT opens up a new
      dimension in orofacial diagnosis. Improvements of the quantity and the exactness
      of diagnostic parameters were attained. The imaging method is helpful and
      indicated in RPE patients with additional diagnostic objectives related to the
      development of occlusion. This imaging method is recommended in borderline cases
      (juvenile or adult patients with questionable sutural response) to determine
      whether the suture is completely open or whether surgical support is needed.

PMID- 17561059
TI  - Dental demineralization associated with gastroesophageal reflux in an orthodontic
      patient.
AB  - Gastroesophageal reflux is a common gastrointestinal disorder that can cause
      irreversible damage to the hard tissues of the teeth. We report an adolescent
      patient with severe dental demineralization associated with gastroesophageal
      reflux during orthodontic treatment. Diagnosis and prevention aspects are
      presented and discussed.

PMID- 17561060
TI  - Orthodontic and surgical treatment of a patient with an ankylosed
      temporomandibular joint.
AB  - This article describes the surgical and orthodontic treatment of a girl with
      facial deformities and functional involvement. The left temporomandibular joint
      was ankylosed, and the lower third of the face was markedly deficient, with
      mandibular retrusion and severe laterognathism to the left side. Mouth-opening
      was limited, and the patient had problems speaking and chewing. Two surgical
      procedures had been performed previously at another institution. We treated the
      patient with condylar surgery while she was still growing, followed by
      orthodontic treatment and orthognathic surgery after growth was complete. Twelve
      year follow-up records are presented.

PMID- 17561061
TI  - Nonsurgical correction of skeletal Class III malocclusion with lateral shift in
      an adult.
AB  - In an adult patient with a severe skeletal Class III malocclusion with midline
      deviation, combined surgical-orthodontic therapy is often the treatment of choice
      because it has a satisfying outcome, and the results tend to be stable.
      Sometimes, however, patients will not accept surgery as a part of the treatment.
      We report a nonsurgical treatment approach and its outcomes for an adult patient
      with a skeletal Class III malocclusion with a lateral shift. Treatment included
      distal movement of the mandibular arch and extraction of the third molars.

PMID- 17561062
TI  - Bluetooth: The invisible connector. Short-range wireless technology for the
      contemporary orthodontic practice.
AB  - Although it sounds like a nonvital tooth, Bluetooth is actually one of
      technology's hottest trends. It is an industrial specification for wireless
      personal area networks, but for a busy orthodontic practice, it translates to
      freedom from cables and cords. Despite its enigmatic name, Bluetooth-based
      devices and the wireless technology that these gadgets work with are here to
      stay. They promise to make life easier for the electronic-device users of all
      stripes, and orthodontists are no exception. The purpose of this article is to
      orient orthodontists, office staff, and auxiliary personnel to this universal
      wireless technology that is slowly becoming an integral part of every office.

PMID- 17561063
TI  - Interaction between pentaethylene glycol n-octyl ether and poly(acrylic acid):
      effect of the polymer molecular weight.
AB  - The effect of the polymer molecular weight on the interaction between
      pentaethylene glycol n-octyl ether (C(8)E(5)) and poly(acrylic acid) (PAA) has
      been investigated by a combined experimental strategy including tensiometry,
      potentiometry, calorimetry, fluorescence quenching and intradiffusion (pulsed
      gradient spin echo-NMR) measurements. PAA samples with an average molecular
      weight varying in a wide range (M (w)=2000, 100,000, 250,000, and 450,000) have
      been considered. The measurements have been performed at constant polymer
      concentration (0.1% w/w) with varying surfactant molality. In all the considered
      systems, at low surfactant concentration, adsorption of surfactant monomers onto
      the polymer chain has been detected. At a C(8)E(5) molality (T(1)) independent of
      the PAA M (w), surfactant molecules start to aggregate, forming clusters to which
      the polymer co-participates. Above this concentration, the behavior of the system
      depends on M (w). In fact, if polymer samples with high molecular weight (M
      (w)100,000) are employed, all the added surfactant aggregates onto the polymer
      leading to the polymer saturation and, subsequently, to free micelles formation.
      Both saturation and free micellization occur at surfactant concentrations which
      are independent of the polymer molecular weight. C(8)E(5) aqueous mixtures
      containing PAA with low molecular weight (M (w)=2000) behaves differently, in
      that, above T(1), only a fraction ( approximately 20%) of the added surfactant
      molecules interact with the polymer, forming aggregates to which more than one
      PAA chain participate. In this case, C(8)E(5) free micellization occurs before
      polymer saturation. The experimental evidences have been interpreted in terms of
      the subtle balance between the various molecular interactions driving the
      surfactant-polymer aggregation.

PMID- 17561064
TI  - Forces and friction between hydrophilic and hydrophobic surfaces: influence of
      oleate species.
AB  - The atomic force microscope has been used to investigate normal surface forces
      and lateral friction forces at different concentrations of sodium oleate, a
      frequently used fatty acid in the deinking process. The measurements have been
      performed using the colloidal probe technique with bead materials consisting of
      cellulose and silica. Cellulose was used together with a printing ink alkyd resin
      and mica, whereas silica was used with a hydrophobized silica wafer. The
      cellulose-alkyd resin system showed stronger double layer repulsion and the
      friction was reduced with increasing surfactant concentration. The adhesive
      interaction disappeared immediately on addition of sodium oleate. The normal
      surface forces for cellulose-mica indicated no apparent adsorption of the sodium
      oleate however, the friction coefficient increased on addition of sodium oleate,
      which we ascribe to some limited adsorption increasing the effective surface
      roughness. The silica-hydrophobic silica system showed a completely different
      surface force behavior at the different concentrations. An attractive hydrophobic
      interaction was evident since the surfaces jumped into adhesive contact at a
      longer distance than the van der Waals forces would predict. The strong adhesion
      was reflected in the friction forces as a nonlinear relationship between load and
      friction and a large friction response at zero applied load. Indirect evidence of
      adsorption to the hydrophilic silica surface was also observed in this case, and
      QCM studies were performed to confirm the adsorption of material to both
      surfaces.

PMID- 17561065
TI  - A note on spin-coating with small evaporation.
AB  - We examine a simple model of spin-coating with "small" evaporation effects and
      using a formal asymptotic approach we improve on previous approximate models.

PMID- 17561066
TI  - Ni(II) complexation to amorphous hydrous ferric oxide: an X-ray absorption
      spectroscopy study.
AB  - Ni(II) sorption onto iron oxides and in particular hydrous ferric oxide (HFO) is
      among the important processes impacting its distribution, mobility, and
      bioavailability in environment. To develop mechanistic models for Ni, extended X
      ray absorption fine structure (EXAFS) analysis has been conducted on Ni(II)
      sorbed to HFO. Coprecipitation revealed the formation of the metastable alpha
      Ni(OH)(2) at a Ni(II) loading of 3.5 x 10(-3) molg(-1). On the other hand, Ni(II)
      formed inner-sphere mononuclear bidentate complexes along edges of FeO(6)
      octahedra when sorbed to HFO surfaces with Ni-O distances of 2.05-2.07 A and Ni
      Fe distances of 3.07-3.11 A. This surface complex was observed by EXAFS study
      over 2.8 x 10(-3) to 10(-1) ionic strength, pH from 6 to 7, a Ni(II) loading of 8
      x 10(-4) to 8.1 x 10(-3) molg(-1) HFO, and reaction times from 4 hours to 8
      months. The short- and long-range structure analyses suggest that the presence of
      Ni(II) inhibited transformation of the amorphous iron oxide into a more
      crystalline form. However, Ni(2+) was not observed to substitute for Fe(3+) in
      the oxide structure. This study systematically addresses Ni(II) adsorption
      mechanisms to amorphous iron oxide. The experimentally defined surface complexes
      can be used to constrain surface complexation modeling for improved prediction of
      metal distribution at the iron oxide/aqueous interface.

PMID- 17561067
TI  - Preparation and characterization of N-isopropylacrylamide/acrylic acid copolymer
      core-shell microgel particles.
AB  - A new method has been developed to prepare smart copolymer microgels that consist
      of well defined temperature sensitive cores and pH sensitive shells. The
      microgels were obtained from N-isopropylacrylamide (NIPAAm) and acrylic acid
      (AAc), containing different mole ratios of AAc. Transmission electron micrographs
      of the microgels show that the colloidal copolymers are nearly monodisperse
      spheres (core-shell structures). The lower critical solution temperatures (LCSTs)
      (or phase separation temperatures) of the aqueous microgel solutions were
      measured by cloud-point method. At slight acidic conditions, the LCST decreased
      with increase in AAc content, which suggests that the hydrophobic group of NIPAAm
      has a greater influence on the LCST than the polar COOH group at those
      conditions. An increase of pH value leads to a significant increase in LCST due
      to the formation of a more hydrophilic copolymer. The LCST were studied as a
      function of copolymer composition over the pH range from 4.0 to 6.5. Because the
      pK(a) of the polymers can be tuned to fall close to neutral pH, these polymer
      compositions can be dispersed to have phase transitions triggered near
      physiological pH or at slight acidic pH values that fall within acidic gradients
      found in biology. Because of their stimuli-responsive behavior, these nanoscale
      materials are excellent candidates for biotechnology and biomedical applications
      where small changes in pH or temperature are of great consequence.

PMID- 17561068
TI  - Al-pillared montmorillonite clay minerals: low-pressure CO adsorption at room
      temperature.
AB  - Three kinds of Al-pillared montmorillonite clay minerals (AlPMON) ion-exchanged
      with cobalt(II), nickel(II), or copper(II) ions were prepared (abbreviated as
      CoAlPMON, NiAlPMON, or CuAlPMON, respectively). For the 673-K- and 873-K-treated
      samples, carbon monoxide (CO) adsorption measurement was performed at room
      temperature under an atmosphere of low CO pressure. The 873-K-treated CuAlPMON
      sample exhibited more efficient adsorption properties for CO molecules, in
      comparison with both-temperatures-treated CoAlPMON and NiAlPMON samples and the
      673-K-treated CuAlPMON sample. In addition, irreversibly adsorbed CO was present
      only on the CuAlPMON sample that had been treated at 873 K; the sites responsible
      for strong CO adsorption were formed in the sample after the pretreatment at the
      higher temperature.

PMID- 17561069
TI  - Use of Fe(3+) ion probe to study the stability of urea-intercalated kaolinite by
      electron paramagnetic resonance.
AB  - The effect of mechanical and chemical activation in processes of urea
      intercalation in the interlayer spacing of kaolinite and the effect of varying
      the temperature of the intercalation product between 100 and 200 degrees C were
      studied using Fe(3+) ions as a probe in electron paramagnetic resonance (EPR)
      spectroscopy. Other techniques were also used to characterize the samples.
      Monitoring the heating of urea-intercalated kaolinite, FTIR, and XRD revealed
      that the product obtained was stable up to a temperature of 150-160 degrees C.
      The EPR data indicated that the intercalation process promoted an approximation
      and increase of the magnetic interactions among the Fe(3+) ions. The DRUV-vis
      analysis of the product before heating showed an absorption band at 680 nm that
      was absent in the raw kaolinite. This band was attributed to the transition A(1)6
      ->T(2)4(G4) in the adjacent Fe(3+) ions, intensified by magnetic coupling among
      these ions. We suggest that intercalated urea forms hydrogen bonds between the
      carbonyl's oxygen and the hydroxyls bound to the Fe(3+) ions of the kaolinite
      structure. This would cause the approximation of the Fe(3+) ions, maximizing
      magnetic couplings and intensifying concentrated centers of Fe(3+), as was
      visible by EPR spectroscopy.

PMID- 17561071
TI  - Indigenous microflora and innate immunity of the head and neck.
AB  - The normal flora of the head and neck exists in a delicate balance within tightly
      regulated ecologic niches, counterbalanced by a highly efficient innate immune
      system of the host. Invasion by the normal oral flora is rare when mucosal
      defenses remain intact. An understanding of the indigenous microflora and the
      innate mucosal defense mechanisms is necessary for an appropriate evaluation of
      infections and therapies in this area.

PMID- 17561072
TI  - Microbiologic investigations for head and neck infections.
AB  - A variety of methods, including direct examination of stained smears, antigen
      detection, routine and special cultures, and histopathologic evaluation are
      available for investigation of head and neck infections. Newer rapid molecular
      techniques with increased sensitivity and specificity are becoming available at
      many centers. Evaluation of specific causes in head and neck infections is
      complicated by the tendency for polymicrobial infections, difficulty in obtaining
      adequate specimens, and the presence of a diverse endogenous microflora at
      various mucosal sites that also can include true pathogens. These aspects of
      laboratory investigation for head and neck infections are reviewed in this
      article.

PMID- 17561073
TI  - Imaging studies for head and neck infections.
AB  - Imaging the head and neck presents a unique challenge because of the dense
      concentration of complex anatomy and the importance of lesion localization in
      formulating the differential diagnosis and prognosis. Critical imaging features
      such as the ability to define fascial borders of soft tissue neck compartments,
      the demonstration of intricate anatomy such as the temporal bones and paranasal
      sinuses, and the noninvasive assessment of vascular integrity have improved
      greatly in recent years in parallel with the rapid technologic advances in
      multidetector CT and MRI. After comparing the available imaging techniques, this
      article explores the imaging findings by anatomic region.

PMID- 17561074
TI  - Microbiology and principles of antimicrobial therapy for head and neck
      infections.
AB  - The principles of antimicrobial management for head and neck infections include
      establishing an accurate clinical and microbiologic diagnosis and treating the
      patient initially with an empiric antimicrobial regimen based on predicted
      likelihood of success and reduced potential for resistance. Subsequent
      adjustments may be required based on clinical response and available culture
      results. This article summarizes the aerobic and anaerobic microbiology of
      selected acute and chronic infections of the head and neck and the approaches to
      antimicrobial therapy.

PMID- 17561075
TI  - Periorbital and orbital infections.
AB  - Practitioners frequently have the opportunity to manage the child for whom the
      chief complaint is a swollen eye. Some children have trivial or self-limited
      disorders, but others can have sight- or life-threatening problems. Noninfectious
      causes of the swollen eye include blunt trauma, tumor, local edema, and allergy.
      Infectious causes can be preseptal or orbital in origin. The differential
      diagnosis and management of these conditions are considered in this article.

PMID- 17561076
TI  - Diagnosis and treatment of acute otitis media: evaluating the evidence.
AB  - Acute otitis media (AOM) is one of the most common illnesses for which children
      in the United States receive an antimicrobial agent. Of the six recommendations
      offered in recent guidelines for treatment of AOM, only one, the assessment and
      treatment of pain with analgesics, is based on strong evidence. This article
      reviews the diagnosis of AOM and the accuracy of various signs and symptoms in
      indicating a bacterial origin, the data on the effect of antimicrobial agents
      compared with placebo in the treatment of AOM, and the gaps in knowledge that
      should be addressed by future research and clinical trials.

PMID- 17561077
TI  - Acute and chronic bacterial sinusitis.
AB  - Sinusitis is one of the most common complaints resulting in physician visits in
      the United States. An antecedent viral infection of the upper respiratory tract
      is the most common presentation. Despite its prevalence, most cases resolve
      spontaneously. Only a small proportion develops a secondary bacterial infection
      that will benefit from antimicrobial therapy. This article discusses the
      microbiology and pathogenesis of acute and chronic bacterial sinusitis. The role
      anaerobic bacterial in chronic and recurrent sinusitis is emphasized, and
      appropriate antimicrobial regimens are discussed.

PMID- 17561078
TI  - Pharyngitis and epiglottitis.
AB  - Acute pharyngitis is one of the most common illnesses for which patients visit
      primary care physicians. Most cases are of viral origin, and with few exceptions
      these illnesses are both benign and self-limited. The most important bacterial
      cause is the beta-hemolytic group A streptococcus. There are other uncommon or
      rare types of pharyngitis. For some of these treatment is required or available,
      and some may be life threatening. Among those discussed in this article are
      diphtheria, gonorrhea, HIV infection, peritonsillar abscess, and epiglottitis.

PMID- 17561079
TI  - Dental caries and periodontitis: contrasting two infections that have medical
      implications.
AB  - Both dental decay and periodontal disease are diagnosable and treatable bacterial
      infections. They are distinctly different infections, with dental decay occurring
      on the supragingival surfaces of the teeth and periodontal infections occurring
      in the gingival tissue approximating the subgingival plaque. The bacteria
      involved and the pathophysiology of these infections are distinctly different.

PMID- 17561080
TI  - Mucositis in the cancer patient and immunosuppressed host.
AB  - Oral mucositis is a serious complication of cancer therapy and in severely
      immunosuppressed patients. In immunosuppressed patients, the signs and symptoms
      of infection often are muted because of limited host response, and accurate
      diagnosis and appropriate treatment may be difficult. Prevention of mucosal
      breakdown, suppression of microbial colonization, control of viral reactivation,
      and effective management of severe xerostomia are all critical steps to reducing
      the overall morbidity and mortality of oromucosal infections.

PMID- 17561081
TI  - Cervical lymphadenitis, suppurative parotitis, thyroiditis, and infected cysts.
AB  - Neck masses are common and have a variety of infectious agents and noninfectious
      causes. This article reviews the more common infectious causes of neck masses
      cervical lymphadenitis, suppurative parotitis, thyroiditis, and infected cysts.
      Important clinical pearls, diagnostic evaluation including laboratory studies,
      and imaging are summarized. Methods for prevention are highlighted.

PMID- 17561082
TI  - Cervicofacial actinomycosis and mandibular osteomyelitis.
AB  - Cervicofacial actinomycosis should be included in the differential diagnosis of
      any soft tissue swelling in the head and neck region, particularly if malignancy
      or a granulomatous disease is suspected. The diagnosis often is overlooked
      because of this entity's ability to mimic other conditions. Mandibular
      osteomyelitis also is underappreciated by many clinicians in their assessment of
      head and neck infections. Most cases are traced to an odontogenic source, with
      periapical tooth abscess and posttraumatic or surgical complication as key
      antecedent events.

PMID- 17561083
TI  - Life-threatening infections of the peripharyngeal and deep fascial spaces of the
      head and neck.
AB  - This article reviews life-threatening infections of the head and neck. It
      discusses the anatomic boundaries, pathophysiologic processes, clinical
      manifestations, potential complications, and suggested therapies of infections of
      the submandibular, lateral pharyngeal, retropharyngeal, prevertebral, and danger
      spaces.

PMID- 17561084
TI  - Vascular and parameningeal infections of the head and neck.
AB  - Vascular and parameningeal infections of the head and neck are rare but
      frequently life threatening. These infections include intracranial and
      extracranial septic venous thrombophlebitis, arterial mycotic aneurysms and
      erosions, subdural empyema, and epidural abscesses. They usually arise as
      complications of otogenic, oropharyngeal, or paranasal sinus infections, and
      management involves an aggressive combined medical-surgical approach.

PMID- 17561085
TI  - Vaccine safety in the neonatal period.
AB  - Administration of two doses of multicomponent vaccine to pups and kittens between
      8 and 16 weeks of age has become a standard and important part of veterinary
      healthcare for this susceptible neonatal population. Currently available vaccine
      formulations conform to high standards of quality, safety and efficacy, but there
      remains a very small risk of adverse effect following vaccination. Quantifying
      this risk is extremely difficult and there are few meaningful data available. It
      would seem, however, that there is a higher prevalence of suspected adverse
      reactions (SARs) following vaccination in the neonatal period than in adult
      animals. The range of reported adverse reactions in neonates is broad, and
      includes: suspected lack of efficacy, mild non-specific and transient illness
      post-vaccination, and the development of hypersensitivity or autoimmune
      reactions. The most common reactions in both species are the various clinical
      manifestations of type I hypersensitivity. These events might relate to the
      induction of IgE antibody specific for extraneous protein incorporated within
      vaccines, in particular bovine serum albumin. That such reactions are most
      prevalent in small breed dogs, that also make the highest serological responses
      to vaccination, suggests a case for the formulation of low-dose products for
      miniature breeds. At least a proportion of neonatal vaccine SARs are related to
      the use of potent immunological adjuvants in certain products. A recent study in
      neonatal kittens has confirmed that non-adjuvanted vaccine induces significantly
      less local vaccine site inflammation than comparable adjuvanted products. The low
      risk of vaccine SARs in early life may therefore be further reduced by
      formulating non-adjuvanted vaccines with reduced content of extraneous protein,
      and by carefully considering the optimum vaccination protocol for any individual
      animal.

PMID- 17561087
TI  - Is vitamin E an antioxidant, a regulator of signal transduction and gene
      expression, or a 'junk' food? Comments on the two accompanying papers: "Molecular
      mechanism of alpha-tocopherol action" by A. Azzi and "Vitamin E, antioxidant and
      nothing more" by M. Traber and J. Atkinson.

PMID- 17561088
TI  - Vitamin E, antioxidant and nothing more.
AB  - All of the naturally occurring vitamin E forms, as well as those of synthetic all
      rac-alpha-tocopherol, have relatively similar antioxidant properties, so why does
      the body prefer alpha-tocopherol as its unique form of vitamin E? We propose the
      hypothesis that all of the observations concerning the in vivo mechanism of
      action of alpha-tocopherol result from its role as a potent lipid-soluble
      antioxidant. The purpose of this review then is to describe the evidence for
      alpha-tocopherol's in vivo function and to make the claim that alpha-tocopherol's
      major vitamin function, if not only function, is that of a peroxyl radical
      scavenger. The importance of this function is to maintain the integrity of long
      chain polyunsaturated fatty acids in the membranes of cells and thus maintain
      their bioactivity. That is to say that these bioactive lipids are important
      signaling molecules and that changes in their amounts, or in their loss due to
      oxidation, are the key cellular events that are responded to by cells. The
      various signaling pathways that have been described by others to be under alpha
      tocopherol regulation appear rather to be dependent on the oxidative stress of
      the cell or tissue under question. Moreover, it seems unlikely that these
      pathways are specifically under the control of alpha-tocopherol given that
      various antioxidants other than alpha-tocopherol and various oxidative stressors
      can manipulate their responses. Thus, virtually all of the variation and scope of
      vitamin E's biological activity can be seen and understood in the light of
      protection of polyunsaturated fatty acids and the membrane qualities (fluidity,
      phase separation, and lipid domains) that polyunsaturated fatty acids bring
      about.

PMID- 17561089
TI  - Molecular mechanism of alpha-tocopherol action.
AB  - The inability of other antioxidants to substitute for alpha-tocopherol in a
      number of cellular reactions, the lack of a compensatory antioxidant response in
      the gene expression under conditions of alpha-tocopherol deficiency, the unique
      uptake of alpha-tocopherol relative to the other tocopherols and its slower
      catabolism, and the striking differences in the molecular function of the
      different tocopherols and tocotrienols, observed in vitro, unrelated to their
      antioxidant properties, are all data in support of a nonantioxidant molecular
      function of alpha-tocopherol. Furthermore, in vivo studies have also shown that
      alpha-tocopherol is not able, at physiological concentrations, to protect against
      oxidant-induced damage or prevent disease allegedly caused by oxidative damage.
      Alpha-tocopherol appears to act as a ligand of not yet identified specific
      proteins (receptors, transcription factors) capable of regulating signal
      transduction and gene expression.

PMID- 17561090
TI  - Platelet-associated NAD(P)H oxidase contributes to the thrombogenic phenotype
      induced by hypercholesterolemia.
AB  - Elevated cholesterol levels promote proinflammatory and prothrombogenic responses
      in venules and impaired endothelium-dependent arteriolar dilation. Although
      NAD(P)H oxidase-derived superoxide has been implicated in the altered vascular
      responses to hypercholesterolemia, it remains unclear whether this oxidative
      pathway mediates the associated arteriolar dysfunction and platelet adhesion in
      venules. Platelet and leukocyte adhesion in cremasteric postcapillary venules and
      arteriolar dilation responses to acetylcholine were monitored in wild-type (WT),
      Cu,Zn-superoxide dismutase transgenic (SOD-TgN), and NAD(P)H oxidase-knockout
      (gp91(phox-/-)) mice placed on a normal (ND) or high-cholesterol (HC) diet for 2
      weeks. HC elicited increased platelet and leukocyte adhesion in WT mice versus
      ND. Cytosolic subunits of NAD(P)H oxidase (p47phox and p67phox) were expressed in
      platelets. This was not altered by hypercholesterolemia; however, platelets and
      leukocytes from HC mice exhibited elevated generation of reactive oxygen species
      compared to ND mice. Hypercholesterolemia-induced leukocyte recruitment was
      attenuated in SOD-TgN-HC and gp91(phox-/-)-HC mice. Recruitment of platelets
      derived from WT-HC mice in venules of SOD-TgN-HC or gp91(phox-/-)-HC recipients
      was comparable to ND levels. Adhesion of SOD-TgN-HC platelets paralleled the
      leukocyte response and was attenuated in SOD-TgN-HC recipients, but not in WT-HC
      recipients. However, gp91(phox-/-)-HC platelets exhibited low levels of adhesion
      comparable to those of WT-ND in both hypercholesterolemic gp91(phox-/-) and WT
      recipients. Arteriolar dysfunction was evident in WT-HC mice, compared to WT-ND.
      Overexpression of SOD or, to a lesser extent, gp91(phox) deficiency restored
      arteriolar vasorelaxation responses toward WT-ND levels. These findings reveal a
      novel role for platelet-associated NAD(P)H oxidase in producing the thrombogenic
      phenotype in hypercholesterolemia and demonstrate that NAD(P)H oxidase-derived
      superoxide mediates the HC-induced arteriolar dysfunction.

PMID- 17561091
TI  - Nox regulation of smooth muscle contraction.
AB  - The catalytic subunit gp91phox (Nox2) of the NADPH oxidase of mammalian
      phagocytes is activated by microbes and immune mediators to produce large amounts
      of reactive oxygen species (ROS) which participate in microbial killing. Homologs
      of gp91phox, the Nox and Duox enzymes, were recently described in a range of
      organisms, including plants, vertebrates, and invertebrates such as Drosophila
      melanogaster. While their enzymology and cell biology are being extensively
      studied in many laboratories, little is known about in vivo functions of Noxes.
      Here, we establish and use an inducible system for RNAi to discover functions of
      dNox, an ortholog of human Nox5 in Drosophila. We report here that depletion of
      dNox in musculature causes retention of mature eggs within ovaries, leading to
      female sterility. In dNox-depleted ovaries and ovaries treated with a Nox
      inhibitor, muscular contractions induced by the neuropeptide proctolin are
      markedly inhibited. This functional defect results from a requirement for dNox
      for the proctolin-induced calcium flux in Drosophila ovaries. Thus, these studies
      demonstrate a novel biological role for Nox-generated ROS in mediating agonist
      induced calcium flux and smooth muscle contraction.

PMID- 17561092
TI  - Nitrative thioredoxin inactivation as a cause of enhanced myocardial
      ischemia/reperfusion injury in the aging heart.
AB  - Several recent studies have demonstrated that thioredoxin (Trx) is an important
      antiapoptotic/cytoprotective molecule. The present study was designed to
      determine whether Trx activity is altered in the aging heart in a way that may
      contribute to increased susceptibility to myocardial ischemia/reperfusion (MI/R).
      Compared to young animals, MI/R-induced cardiomyocyte apoptosis and infarct size
      were increased in aging animals (p<0.01). Trx activity was decreased in the aging
      heart before MI/R, and this difference was further amplified after MI/R. Trx
      expression was moderately increased and Trx nitration, a posttranslational
      modification that inhibits Trx activity, was increased in the aging heart.
      Moreover, Trx-aptosis-regulating kinase-1 (Trx-ASK1) complex formation was
      reduced and activity of p38 mitogen-activated protein kinase (MAPK) was
      increased. Treatment with FP15 (a peroxynitrite decomposition catalyst) reduced
      Trx nitration, increased Trx activity, restored Trx-ASK1 interaction, reduced P38
      MAPK activity, attenuated caspase 3 activation, and reduced infarct size in aging
      animals (p<0.01). Our results demonstrated that Trx activity is decreased in the
      aging heart by posttranslational nitrative modification. Interventions that
      restore Trx activity in the aging heart may be novel therapies to attenuate MI/R
      injury in aging patients.

PMID- 17561093
TI  - Sodium salicylate prevents paraquat-induced apoptosis in the rat lung.
AB  - The nonselective contact herbicide, paraquat (PQ), is a strong pneumotoxicant,
      especially due to its accumulation in the lung through a polyamine uptake system
      and to its capacity to induce redox cycling, leading to oxidative stress-related
      damage. In the present study, we aimed to investigate the occurrence of apoptotic
      events in the lungs of male Wistar rats, 24, 48, and 96 h after PQ exposure (25
      mg/kg ip) as well as the putative healing effects provided by sodium salicylate
      [(NaSAL), 200 mg/kg ip] when administered 2 h after PQ. PQ exposure resulted in
      marked lung apoptosis, in a time-dependent manner, characterized by the "ladder
      like" pattern of DNA observed through electrophoresis and by the presence of
      terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end
      labeling (TUNEL)-positive cells (TPC) as revealed by immunohistochemistry. The
      two main caspase cascades (the extrinsic receptor-mediated and the intrinsic
      mitochondria-mediated) and the expressions of p53 and activator protein-1 (AP-1)
      were also evaluated, to obtain an insight into apoptotic cellular signaling. PQ
      exposed rats suffered a time-dependent increase of caspase-3 and caspase-8 and a
      decrease of caspase-1 activities in lungs compared to the control group. A marked
      mitochondrial dysfunction evidenced by cytochrome c (Cyt c) release was also
      observed as a consequence of PQ exposure. In addition, fluorescence
      electrophoretic mobility shift assay (fEMSA) revealed a transcriptional induction
      of the p53 and AP-1 transcription factors in a time-dependent manner as a
      consequence of PQ exposure. NaSAL treatment resulted in the remission of the
      observed apoptotic signaling and consequently of lung apoptosis. Taken together,
      the present results showed that PQ activates several events involved in the
      apoptotic pathways, which might contribute to its lung toxicodynamics. NaSAL, a
      recently implemented antidote for PQ intoxications, proved to protect lungs from
      PQ-induced apoptosis.

PMID- 17561094
TI  - Characterization of redox state and reductase activity of protein disulfide
      isomerase under different redox environments using a sensitive fluorescent assay.
AB  - In this study, dieosin glutathione disulfide (Di-E-GSSG) was synthesized by the
      reaction of eosin isothiocyanate with GSSG. Di-E-GSSG had low fluorescence which
      increased approximately 70-fold on reduction of its disulfide bond. The substrate
      was used to monitor the disulfide reductase activity of PDI. Di-E-GSSG is the
      most sensitive pseudo substrate for PDI reductase activity reported to date. This
      probe was further used as an analytical reagent to develop an end point assay for
      measuring the redox state of PDI. The reduction of Di-E-GSSG by reduced enzyme
      was studied in the absence of reducing agents and the redox state of PDI was
      monitored as a function of the stoichiometric changes in the amount of eosin
      glutathione (EGSH) generated by the active-site dithiols of PDI. The redox state
      of PDI was also studied under variable [GSH]/[GSSG] ratios. The results indicate
      that PDI is in approximately 1/2-reduced state where the [GSH]/[GSSG] ratio is
      between 1:1 and 3:1, conditions similar to the lumen of endoplasmic reticulum or
      in the extracellular environment. On the other hand, [GSH]/[GSSG] ratios of > or
      =8:1, such as in cytosol, all active-site thiols would be reduced. The study was
      extended to utilize Di-E-GSSG to investigate the effect of variable redox ratios
      on the platelet surface PDI reductase activity.

PMID- 17561095
TI  - Phase 2 enzyme induction by conjugated linoleic acid improves lupus-associated
      oxidative stress.
AB  - Conjugated linoleic acid (CLA) exhibits anticancer and anti-inflammatory
      properties. Its ability to increase total GSH (GSH+GSSG) amount and gamma
      glutamylcysteine ligase (gammaGCL) protein expression was recently associated
      with the inhibition of typical pathological signs in MRL/MpJ-Fas(lpr) mice
      (MRL/lpr). In the present study the ability of CLA to modulate oxidative stress
      and phase 2 enzyme activity in the same animal model was investigated. Disease
      severity was associated with age-dependent production of anti-double-stranded DNA
      antibodies (anti-dsDNA IgGs) and with enhanced extent of oxidative stress
      markers: reduced total GSH, increased protein 3-nitrotyrosines (3-NT), and
      protein-bound carbonyl (PC) amounts. To examine the effect of CLA on antioxidant
      status, CLA or olive oil (as control) was administered to pregnant MRL/lpr mice.
      Significantly higher total GSH and Trolox equivalent antioxidant capacity (TEAC)
      levels were measured in serum of CLA-treated dams (and their pups), as compared
      with controls. Finally, the antioxidant and chemopreventive properties of CLA
      were investigated in old MRL/lpr mice. Sera of CLA-treated mice contained higher
      concentrations of total GSH which were negatively correlated with the levels of
      oxidative stress markers. Moreover, increased GSH, gammaGCL, glutathione S
      transferase (GSTs), and NAD(P)H:quinone oxidoreductase (NQO1) activities were
      measured in liver and spleen of CLA-treated animals. In conclusion our data
      indicate that the activation of detoxifying enzymes may be one of the mechanisms
      whereby dietary CLA down-regulates oxidative stress in MRL/lpr mice.

PMID- 17561096
TI  - MAO-A-induced mitogenic signaling is mediated by reactive oxygen species, MMP-2,
      and the sphingolipid pathway.
AB  - The degradation of biogenic amines by monoamine oxidase A (MAO-A) generates
      reactive oxygen species (ROS) which participate in serotonin and tyramine
      signaling. This study aimed to investigate the role of ROS in the mitogenic
      signaling activated during tyramine and serotonin oxidation by MAO-A in smooth
      muscle cells (SMC). Incubation of SMC with serotonin or tyramine induced
      intracellular ROS generation, and a signaling cascade involving metalloproteases
      and the neutral sphingomyelinase-2 (nSMase2, the initial step of the sphingolipid
      pathway), ERK1/2 phosphorylation, and DNA synthesis. Silencing MAO-A by siRNA,
      pharmacological MAO-A inhibitors (pargyline and Ro41-1049), and the
      antioxidant/ROS scavenger butylated hydroxytoluene (BHT) inhibited the signaling
      cascade, suggesting that ROS generated during tyramine oxidation by MAO-A are
      required. The MMP inhibitor Batimastat, MMP2-specific siRNA, and MMP2 deletion
      (MMP2(-/-) fibroblasts) blocked nSMase activation and SMC proliferation,
      suggesting a role for MMP2 in this signaling pathway. Silencing nSMase2 by siRNA
      did not inhibit ROS generation and MMP2 activation, but blocked SMC proliferation
      induced by tyramine, suggesting that nSMase2 is downstream MMP2. These findings
      demonstrate that H(2)O(2)-generated during tyramine oxidation by MAO-A triggers a
      stress-induced mitogenic signaling via the MMP2/sphingolipid pathway, which could
      participate in excessive remodeling and alteration of the vascular wall.

PMID- 17561097
TI  - Redox-signaling transmitted in trans to neighboring cells by melanoma-derived TNF
      containing exosomes.
AB  - Hydrogen peroxide is known to be involved in redox signaling pathways that
      regulate normal processes and disease progression, including cytokine signaling,
      oxidative stress, and cancer. In studies on immune surveillance against cancer,
      hydrogen peroxide was found to disrupt cytotoxic T-cell function, thus
      contributing to tumor escape. In this study, secretion of TNF-containing vesicles
      of rab9+ endosomal origin, termed exosomes, was investigated using GFP-TNF
      constructs. We observed a polarized intracellular trafficking and apical
      secretion of TNF-positive nanovesicles. Cell-to-cell transfer of TNF was observed
      in exosomes in real-time microscopy, occurring separate from the
      melanin/melanosome compartment. Exosomes were prepared by ultracentrifugation or
      immunoisolation on anti-beta2-microglobulin magnetic beads. TNF as well as TNF
      receptors 1 and 2 were present in the exosomes as determined by Western blot,
      flow cytometry, and deconvolution microscopy. The functional significance of
      melanoma-derived exosomes was established by their signaling competence with
      ability to generate significantly higher ROS levels in T cells compared with sham
      exosomes (P=0.0006). In conclusion, we report here, for the first time, that TNF
      is found in tumor cell-derived exosomes and that these exosomes transmit redox
      signaling in trans to neighboring cells. The results are of importance for a
      better understanding of tumor escape mechanisms.

PMID- 17561098
TI  - Oxidation sensitivity of the catalytic cysteine of the protein-tyrosine
      phosphatases SHP-1 and SHP-2.
AB  - Reversible oxidation of the catalytic cysteine of protein-tyrosine phosphatases
      (PTPs) has emerged as a putative mechanism of activity regulation by
      physiological cell stimulation with growth factors, and by cell treatments with
      adverse agents such as UV irradiation. We compared SHP-1 and SHP-2, two
      structurally related cytoplasmic protein-tyrosine phosphatases with different
      cellular functions and cell-specific expression patterns, for their intrinsic
      susceptibility to oxidation by H(2)O(2). The extent of oxidation was monitored by
      detecting the modification of the PTP catalytic cysteine by three different
      methods, including a modified in-gel PTP assay, alkylation with a biotinylated
      iodoacetic acid derivative, and an antibody against oxidized PTPs. Dose-response
      curves for oxidation of the catalytic domains of SHP-1 and SHP-2 were similar.
      SHP-1 and -2 require relatively high H(2)O(2) concentrations for oxidation (half
      maximal oxidation at 0.1-0.5 mM). For SHP-1, the SH2 domains had a significant
      protective function with respect to oxidation. In EOL-1 cells, SHP oxidation by
      exogenous H(2)O(2) in general and SHP-2 oxidation in particular was strongly
      diminished compared to HEK293 cells, at least partially related to a generally
      lower oxidant sensitivity of the EOL-1 cells. The data suggest that the
      differential cell functions of SHP-1 and SHP-2 are not related to differences in
      oxidation sensitivity. The modulating effects of SH2 domains for oxidation of
      these PTPs are in support of an enhanced oxidation susceptibility of activated
      SHPs.

PMID- 17561099
TI  - Synthesis and properties of novel porphyrin spin probes containing isoindoline
      nitroxides.
AB  - We report the synthesis of novel spin-labeled porphyrins containing isoindoline
      nitroxides (TMIO-APTPP and TMIO-APTSPP) and their manganese complexes (Mn-TMIO
      APTPP and Mn-TMIO-APTSPP). These compounds represent potential new tools for
      electron paramagnetic resonance (EPR) as well as novel spin probes. Both TMIO
      APTPP and TMIO-APTSPP have characteristic UV absorption peaks of free base
      porphyrin, while the characteristic absorption peaks of their manganese complexes
      Mn-TMIO-APTPP and Mn-TMIO-APTSPP shifted to shorter wavelengths. Electron
      paramagnetic resonance (EPR) spectroscopy indicated that these compounds all
      exhibit hyperfine splittings characteristic of EPR spectra of
      tetramethylisoindoline nitroxides, the typical nitroxide g values of
      approximately 2.006, and nitrogen isotropic hyperfine coupling constants (a(N)
      values) of about 14 G (293 K). The observed linewidths (La) for TMIO-APTSPP (0.73
      G) and Mn-TMIO-APTSPP (0.65 G) in distilled water are significantly narrower than
      for TMIO-APTPP (1.475 G) and Mn-TMIO-APTPP (1.55 G) in chloroform.

PMID- 17561101
TI  - Cellular response to infrared radiation involves retrograde mitochondrial
      signaling.
AB  - Infrared A radiation (IRA) is a major component of sunlight. Similar to
      ultraviolet (UV) B and UVA, IRA induces gene transcription. In contrast to the UV
      response very little is known about the IRA response. In the present study, IRA
      induced expression of matrix metalloproteinase-1 (MMP-1) was found to be mediated
      by the formation of intracellular reactive oxygen species (ROS). Staining of IRA
      irradiated cells with MitoSox revealed an increase in mitochondrial superoxide
      anion production and treatment of fibroblasts with the mitochondrial targeted
      antioxidant MitoQ completely abrogated the IRA, but not the UVB or UVA1,
      response. ROS relevant for IRA-induced signaling originated from the mt electron
      transport chain, because (i) chemical inhibition of the electron transport chain
      prevented IRA, but not UVB or UVA1, radiation-induced MMP-1 expression, (ii) rho0
      fibroblasts specifically failed to increase MMP-1 expression in response to IRA,
      and (iii) peroxisome proliferator-activated receptor gamma coactivator-1 (PGC-1)
      overexpressing fibroblasts with increased electron transport chain content were
      hypersensitive to IRA radiation-induced gene expression. Thus, IRA, in contrast
      to UV, elicits a retrograde signaling response in human skin.

PMID- 17561100
TI  - HIF-1alpha activation by a redox-sensitive pathway mediates cyanide-induced BNIP3
      upregulation and mitochondrial-dependent cell death.
AB  - Cyanide produces degeneration of the nervous system in which different modes of
      cell death are activated in the vulnerable brain areas. In brain, the mechanism
      underlying the cell death is not clear. In this study, an immortalized
      dopaminergic cell line was used to characterize the cell death signaling cascade
      activated by cyanide. Cyanide-treated cells exhibited a time- and concentration
      dependent apoptosis that was caspase independent. Cyanide induced a rapid surge
      of intracellular reactive oxygen species (ROS) generation, followed by p38
      mitogen-activated protein kinase (MAPK) activation and nuclear accumulation of
      hypoxia-inducible factor-1alpha (HIF-1alpha). Activation of p38 MAPK and HIF
      1alpha accumulation were attenuated by N-acetyl-L-cysteine (antioxidant),
      catalase (hydrogen peroxide scavenger), or a selective p38 MAPK inhibitor
      (SB203580). Cyanide activated the hypoxia response element (HRE) promoter, which
      was also blocked by the antioxidants and SB203580. HRE activation was followed by
      increased BNIP3 gene transcription, as reflected by elevated BNIP3 mRNA and
      protein levels. BNIP3 upregulation was reduced by selective RNAi knockdown of HIF
      1alpha. Overexpression of BNIP3 produced mitochondrial dysfunction (reduced
      membrane potential), caspase-independent apoptosis, and sensitization of the
      cells to cyanide-induced toxicity. Expression of a dominant-negative mutant or
      RNAi knockdown of BNIP3 protected the cells from cyanide. It was concluded that
      cyanide activated the HIF-1alpha-mediated pathway of BNIP3 induction through a
      redox-sensitive process. Increased BNIP3 expression then served as an initiator
      of mitochondrial-mediated death.

PMID- 17561102
TI  - Ionizing radiation induces a Yap1-dependent peroxide stress response in yeast.
AB  - Repair of DNA damage is fundamental for cellular tolerance to ionizing radiation
      (IR) and many IR-induced DNA lesions are thought to occur as a result of
      oxidative stress. We investigated the physiological effects of IR in
      Saccharomyces cerevisiae by performing protein expression profiles in cells
      exposed to electron pulse irradiation. Transient induction of several antioxidant
      enzymes in wild-type cells, but not in cells lacking the oxidative stress
      regulator Yap1, indicated that IR exposure causes cellular oxidative stress. Yap1
      activation involved oxidation to the intramolecular disulfide bond, a signature
      of activation by peroxide, and was dependent on the Yap1 peroxide sensor
      Orp1/Gpx3. H(2)O(2) was produced in the culture medium of irradiated cells and
      was both necessary and sufficient for IR-induced Yap1 activation. When IR was
      performed in the presence of N(2)O, obviating H(2)O(2) production and increasing
      hydroxyl radical ((*)OH) production, the Yap1 response was lost, indicating that
      Yap1 was unable to respond to (*)OH or (*)OH-induced damage. However, the Yap1
      response to IR did not seem to be a primary determinant of cellular IR tolerance.
      Altogether, these data provide a molecular demonstration that cells experience in
      vivo peroxide stress during IR and indicate that the H(2)O(2) produced cannot
      account for IR toxicity.

PMID- 17561103
TI  - Low intensity training decreases markers of oxidative stress in skeletal muscle
      of mdx mice.
AB  - Reactive oxygen species may contribute to the pathogenesis of muscular dystrophy.
      High intensity exercise clearly induces muscle damage in mdx mice; however, the
      effects of low intensity exercise training (LIT) on mdx muscle are less clear. We
      examined the effect of LIT on markers of oxidative stress (malondialdehyde and
      protein carbonyls), antioxidant (superoxide dismutase, catalase, and glutathione
      peroxidase), and mitochondrial (2-oxoglutarate dehydrogenase and cytochrome
      oxidase) enzymes in skeletal muscle of mdx and wild-type mice. Mdx and wild-type
      mice were allocated to LIT and sedentary groups. Malondialdehyde levels were
      higher in white muscle from sedentary mdx as compared to both sedentary and LIT
      wild-type mice (P<0.001). Protein carbonyl content was higher in white and red
      muscle of mdx versus wild-type mice (P<0.05). LIT was associated with lower
      levels of malondialdehyde and protein carbonyls in white muscle of mdx mice
      (decreased 38 and 44%, P<0.001 and P<0.01, respectively). Antioxidant and
      mitochondrial enzyme activities were higher in white muscle of mdx than in wild
      type mice (P<0.05). LIT in mdx mice induced physiological adaptation resulting in
      lower levels of markers of oxidative stress that were not different than those
      from wild type. These results are of relevance for therapeutic exercise in
      patients with dystrophinopathy where exercise prescription remains controversial.

PMID- 17561104
TI  - The preferences of the honeybee (Apis mellifera) for different visual cues during
      the learning process.
AB  - By working with very simple images, a number of different visual cues used by the
      honeybee have been described over the past decades. In most of the work, the bees
      had no control over the choice of the images, and it was not clear whether they
      learned the rewarded pattern or the difference between two images. Preferences
      were known to exist when untrained bees selected one pattern from a variety of
      them, but because the preferences of the bees were ignored, it was not possible
      to understand how natural images displaying several cues were detected. The
      preferences were also essential to make a computer model of the visual system.
      Therefore experiments were devised to show the order of preference for the known
      cues in the training situation. Freely flying bees were trained to discriminate
      between a rewarded target with one pattern on the left side and a different one
      on the right, versus a white or neutral target. This arrangement gave the bees a
      choice of what to learn. Tests showed that in some cases they learned two or
      three cues simultaneously; in other cases the bees learned one, or they preferred
      to avoid the unrewarded target. By testing with different combinations of
      patterns, it was possible to put the cues into an order of preference. Of the
      known cues, loosely or tightly attached to eye coordinates, a black or blue spot
      was the most preferred, followed by strong modulation caused by edges, the
      orientation of parallel bars, six equally spaced spokes, a clean white target,
      and then a square cross and a ring. A patch of blue colour was preferred to
      yellow.

PMID- 17561105
TI  - Computational intelligence in earth and environmental sciences.

PMID- 17561106
TI  - Improving weather radar estimates of rainfall using feed-forward neural networks.
AB  - In this paper an approach is described to improve weather radar estimates of
      rainfall based on a neural network technique. Other than rain gauges which
      measure the rain rate R directly on the ground, the weather radar measures the
      reflectivity Z aloft and the rain rate has to be determined over a Z-R
      relationship. Besides the fact that the rain rate has to be estimated from the
      reflectivity many other sources of possible errors are inherent to the radar
      system. In other words the radar measurements contain an amount of observation
      noise which makes it a demanding task to train the network properly. A feed
      forward neural network with Z values as input vector was trained to predict the
      rain rate R on the ground. The results indicate that the model is able to
      generalize and the determined input-output relationship is also representative
      for other sites nearby with similar conditions.

PMID- 17561107
TI  - Differential expression of sarcolipin protein during muscle development and
      cardiac pathophysiology.
AB  - Sarcolipin (SLN) is a small molecular weight sarcoplasmic reticulum (SR) membrane
      protein expressed both in cardiac and skeletal muscle tissues. Recent studies
      using transgenic mouse models have demonstrated that SLN is an important
      regulator of cardiac SR Ca2+ ATPase 2a (SERCA2a). However, there is a paucity of
      information regarding the SLN protein expression in small versus larger mammals
      and its regulation during development and cardiac pathophysiology. Therefore, the
      major goal of this study was to generate an SLN specific antibody and perform
      detailed analyses of SLN protein expression during muscle development and in the
      diseased myocardium. The important findings of the present study are: (i) in
      small mammals, SLN expression is predominant in the atria but low in the
      ventricle and in skeletal muscle tissues, whereas in large mammals, SLN is quite
      abundant in skeletal muscle tissues than the atria, (ii) SLN and SERCA2a are co
      expressed in all striated muscle tissues studied except ventricle and co
      ordinately regulated during muscle development and (iii) SLN protein levels are
      approximately 3 fold upregulated in the atria of heart failure dogs and
      approximately 30% decreased in the atria of hearts prone to myocardial ischemia.
      In addition we found that in the phospholamban null atria, SLN protein levels are
      upregulated.

PMID- 17561108
TI  - IK1 and cardiac hypoxia: after the long and short QT syndromes, what else can go
      wrong with the inward rectifier K+ currents?

PMID- 17561109
TI  - Isw1 acts independently of the Isw1a and Isw1b complexes in regulating
      transcriptional silencing at the ribosomal DNA locus in Saccharomyces cerevisiae.
AB  - Transcriptional silencing of Pol II-transcribed genes in Saccharomyces cerevisiae
      occurs at the HM loci, telomeres and ribosomal DNA (rDNA) locus. Gene silencing
      at these loci requires histone-modifying enzymes as well as factors that regulate
      local chromatin structure. Previous work has shown that the ATP-dependent
      chromatin remodeling protein Isw1 is required for silencing of a marker gene
      inserted at the HMR locus, but not at telomeres. Here we show that Isw1 is
      required for transcriptional silencing of Pol II-transcribed genes in the
      ribosomal DNA locus. Our results indicate that Isw1 associates with the rDNA and
      that this interaction is not altered in cells lacking other members of the Isw1a
      and Isw1b chromatin remodeling complexes. Further, the association of Isw1 with
      the rDNA is not altered in cells lacking the histone deacetylase Sir2 or the
      histone methyltransferase Set1, two factors that are required for gene silencing
      at the rDNA. Notably, the loss of transcriptional silencing at the rDNA in cells
      lacking Isw1 is correlated with a change in rDNA chromatin structure. Together,
      our data support a model in which Isw1 acts independently of the previously
      characterized Isw1a and Isw1b complexes to maintain a heterochromatin-like
      structure at the rDNA that is required for gene silencing.

PMID- 17561110
TI  - Crystal structure of the parasite protease inhibitor chagasin in complex with a
      host target cysteine protease.
AB  - Chagasin is a protein produced by Trypanosoma cruzi, the parasite that causes
      Chagas' disease. This small protein belongs to a recently defined family of
      cysteine protease inhibitors. Although resembling well-known inhibitors like the
      cystatins in size (110 amino acid residues) and function (they all inhibit papain
      like (C1 family) proteases), it has a unique amino acid sequence and structure.
      We have crystallized and solved the structure of chagasin in complex with the
      host cysteine protease, cathepsin L, at 1.75 A resolution. An inhibitory wedge
      composed of three loops (L2, L4, and L6) forms a number of contacts responsible
      for high-affinity binding (K(i), 39 pM) to the enzyme. All three loops interact
      with the catalytic groove, with the central loop L2 inserted directly into the
      catalytic center. Loops L4 and L6 embrace the enzyme molecule from both sides and
      exhibit distinctly different patterns of protein-protein recognition. Comparison
      with a 1.7 A structure of uncomplexed chagasin, also determined in this study,
      demonstrates that a conformational change of the first binding loop (L4) allows
      extended binding to the non-primed substrate pockets of the enzyme active site
      cleft, thereby providing a substantial part of the inhibitory surface. The mode
      of chagasin binding is generally similar, albeit distinctly different in detail,
      when compared to those displayed by cystatins and the cysteine protease
      inhibitory p41 fragment of the invariant chain. The chagasin-cathepsin L complex
      structure provides details of how the parasite protein inhibits a host enzyme of
      possible importance in host defense. The high level of structural and functional
      similarity between cathepsin L and the T. cruzi enzyme cruzipain gives clues to
      how the cysteine protease activity of the parasite can be targeted. This
      information will aid in the development of synthetic inhibitors for use as
      potential drugs for the treatment of Chagas disease.

PMID- 17561111
TI  - Crystal structure of the stationary phase survival protein SurE with metal ion
      and AMP.
AB  - The stationary phase survival protein SurE is a metal ion-dependent phosphatase
      distributed among eubacteria, archaea, and eukaryotes. In Escherichia coli, SurE
      has activities as nucleotidase and exopolyphosphatase, and is thought to be
      involved in stress response. However, its physiological role and reaction
      mechanism are unclear. We report here the crystal structures of the tetramer of
      SurE from Thermus thermophilus HB8 (TtSurE) both alone and crystallized with
      Mn(2+) and substrate AMP. In the presence of Mn(2+) and AMP, differences between
      the protomers were observed in the active site and in the loop located near the
      active site; AMP-bound active sites with the loops in a novel open conformation
      were found in the two protomers, and AMP-free active sites with the loops in a
      conventional closed conformation were found in the other two protomers. The two
      loops in the open conformation are entwined with each other, and this entwining
      is suggested to be required for enzymatic activity by site-directed mutagenesis.
      TtSurE exists as an equilibrium mixture of dimer and tetramer in solution. The
      loop-entwined structure indicates that SurE acts as a tetramer. The structural
      features and the absence of negative cooperativity imply the half-of-the-sites
      reactivity mechanism resulting from a pre-existing tendency toward structural
      asymmetry.

PMID- 17561112
TI  - Engineered I-CreI derivatives cleaving sequences from the human XPC gene can
      induce highly efficient gene correction in mammalian cells.
AB  - Meganucleases are sequence-specific endonucleases which recognize large (>12 bp)
      target sites in living cells and can stimulate homologous gene targeting by a
      1000-fold factor at the cleaved locus. We have recently described a combinatorial
      approach to redesign the I-CreI meganuclease DNA-binding interface, in order to
      target chosen sequences. However, engineering was limited to the protein regions
      shown to directly interact with DNA in a base-specific manner. Here, we take
      advantage of I-CreI natural degeneracy, and of additional refinement steps to
      extend the number of sequences that can be efficiently cleaved. We searched the
      sequence of the human XPC gene, involved in the disease Xeroderma Pigmentosum
      (XP), for potential targets, and chose three sequences that differed from the I
      CreI cleavage site over their entire length, including the central four base
      pairs, whose role in the DNA/protein recognition and cleavage steps remains very
      elusive. Two out of these targets could be cleaved by engineered I-CreI
      derivatives, and we could improve the activity of weak novel meganucleases, to
      eventually match the activity of the parental I-CreI scaffold. The novel proteins
      maintain a narrow cleavage pattern for cognate targets, showing that the
      extensive redesign of the I-CreI protein was not made at the expense of its
      specificity. Finally, we used a chromosomal reporter system in CHO-K1 cells to
      compare the gene targeting frequencies induced by natural and engineered
      meganucleases. Tailored I-CreI derivatives cleaving sequences from the XPC gene
      were found to induce high levels of gene targeting, similar to the I-CreI
      scaffold or the I-SceI "gold standard". This is the first time an engineered
      homing endonuclease has been used to modify a chromosomal locus.

PMID- 17561113
TI  - On the dynamic nature of the transition state for protein-protein association as
      determined by double-mutant cycle analysis and simulation.
AB  - The process of protein-protein association starts with their random collision,
      which may develop into an encounter complex followed by a transition state and
      final complex formation. Here we aim to experimentally characterize the nature of
      the transition state of protein-protein association for three different protein
      protein interactions; Barnase-Barstar, TEM1-BLIP and IFNalpha2-IFNAR2, and use
      the data to model the transition state structures. To model the transition state,
      we determined inter-protein distance-constraints of the activated complex by
      using double mutant cycles (DMC) assuming that interacting residues are spatially
      close. Significant DeltaDeltaG(double dagger)(int) values were obtained only
      between residues on Barnase and Barstar. However, introducing specific mutations
      that optimize the charge complementarity between BLIP and TEM1 resulted in the
      introduction of significant DeltaDeltaG(double dagger)(int) values also between
      residues of these two proteins. While electrostatic interactions make major
      contributions towards stabilizing the transition state, we show two examples
      where steric hindrance exerts an effect on the transition state as well. To model
      the transition-state structures from the experimental DeltaDeltaG(double
      dagger)(int) values, we introduced a method for structure perturbation, searching
      for those inter-protein orientations that best support the experimental
      DeltaDeltaG(double dagger)(int) values. Two types of transition states were
      found, specific as observed for Barnase-Barstar and the electrostatically
      optimized TEM1-BLIP mutants, and diffusive as shown for wild-type TEM1-BLIP and
      IFNalpha2-IFNAR2. The specific transition states are characterized by defined
      inter-protein orientations, which cannot be modeled for the diffusive transition
      states. Mutations introduced through rational design can change the transition
      state from diffusive to specific. Together, these data provide a structural view
      of the mechanism allowing rates of association to differ by five orders of
      magnitude between different protein complexes.

PMID- 17561114
TI  - Effect of small bowel perforation during laparoscopy on end-tidal carbon dioxide:
      observation in a small animal model.
AB  - INTRODUCTION: There are currently no reports in the literature regarding changes
      in end-tidal carbon dioxide (ETCO(2)) when the small bowel is deliberately or
      inadvertently perforated during laparoscopic surgery. The aim of this study was
      to assess the influence of small bowel perforation during laparoscopy on ETCO(2)
      in a rat model. MATERIALS AND METHODS: Two groups of Wistar rats (n = 8/group)
      were anesthetized, tracheostomized, and mechanically ventilated at a fixed tidal
      volume and respiratory rate. After a stabilization phase of 30 min, CO(2)
      pneumoperitoneum was established to 5 mmHg in one group and 12 mmHg in the other
      group, and maintained for 30 min. A small bowel perforation was then created and
      pneumoperitoneum was reestablished for another 30 min. Blood pressure, heart
      rate, peak ventilatory pressure, and ETCO(2) were recorded throughout the
      experiment. RESULTS: No significant changes in blood pressure throughout the
      experiment were noted in either group. The ventilatory pressure increased in both
      groups after the induction of pneumoperitoneum. In the 5 mmHg group, there was a
      modest increase in ETCO(2) following the induction of pneumoperitoneum (from 39.4
      +/- 1.9 to 41.1 +/- 1.4, P = 0.014), and a further increase following the small
      bowel perforation (from 41.1 +/- 1.4 to 42 +/- 0.8, P = 0.007). In the 12 mmHg
      group, there was no change in ETCO(2) after the induction of pneumoperitoneum;
      however, there was a substantial increase in ETCO(2) following bowel perforation
      (35.0 +/- 2.0 to 49.8 +/- 7.1, P = 0.002). CONCLUSIONS: ETCO(2) increases when
      the small bowel is perforated during CO(2) pneumoperitoneum. This increase seems
      more substantial under higher pneumoperitoneal pressures. Small bowel injury may
      enable the diffusion of CO(2) through the bowel mucosa, causing ETCO(2)
      elevation. Therefore, an abrupt increase in ETCO(2) observed during laparoscopy
      may indicate small bowel injury.

PMID- 17561115
TI  - Liver resection-associated macrophage inflammatory protein-2 stimulates
      engraftment but not growth of colorectal metastasis at extrahepatic sites.
AB  - BACKGROUND: Previous studies have shown that liver resection enhances
      intrahepatic engraftment of CXCR-2-expressing colorectal cancer cells by the
      action of the CXC chemokine macrophage inflammatory protein (MIP)-2. Herein we
      studied how liver resection-associated MIP-2 affects extrahepatic tumor cell
      engraftment and whether MIP-2 also stimulates the growth of already established
      metastases. MATERIALS AND METHODS: Green fluorescent protein-transfected CT26.WT
      colorectal cancer cells were implanted into dorsal skinfold chambers of syngeneic
      BALB/c mice. Additionally, all animals underwent a 30% hepatectomy. To study MIP
      2 in extrahepatic tumor cell engraftment, animals were treated with an anti-MIP-2
      antibody, starting at the day of tumor cell implantation. To study MIP-2 in
      established metastases, anti-MIP-2 treatment was initiated at day 5 after tumor
      cell implantation. Hepatectomized animals without neutralization of MIP-2 served
      as controls. Tumor vascularization and growth as well as tumor cell migration,
      proliferation, apoptosis, and CXCR-2 expression were studied over 14 days using
      intravital fluorescence microscopy, histology, and immunohistochemistry. RESULTS:
      Functional inhibition of MIP-2 significantly delayed extrahepatic tumor cell
      engraftment but not the growth of established metastases. The initial delay of
      engraftment was associated with a compensatory stimulation of vascularization and
      tumor cell migration when compared to controls (P < 0.05). Further, inhibition of
      tumor cell engraftment by initial anti-MIP-2 treatment was associated with a
      significant (P < 0.05) reduction of CXCR-2 expression and tumor cell apoptosis.
      CONCLUSION: Our study indicates that MIP-2 is involved in extrahepatic
      engraftment of CT.26 colorectal cancer cells. The MIP-2/CXCR-2 signaling pathway
      may be a promising target for early antitumor therapy in patients undergoing
      liver resection.

PMID- 17561116
TI  - Minimally invasive video-assisted kidney transplantation (MIVAKT).
AB  - BACKGROUND: Minimally invasive surgery has been applied to nearly all fields of
      surgery due to its advantages such as reduced morbidity, a better cosmetic
      outcome, and early recovery. The recent advances in its technique have allowed us
      to use modified minimally invasive surgery technique in the field of kidney
      transplantation. MATERIALS AND METHODS: From January 2004 to March 2006,
      minimally invasive video-assisted kidney transplantation was carried out in 20
      patients. Many clinical variables were compared with the conventional method. The
      operative procedure began with a 7 to 8 cm skin incision. A laparoscopic balloon
      dissector was used to create the retroperitoneal space for the placement of the
      grafted kidney. Vascular anastomosis and ureteroneocystostomy were performed
      under direct vision and with video-assisted TV monitoring. RESULTS: The average
      length of the wound was 7.8 cm and it was placed below the belt line. The average
      operating time was 186 min. Less analgesic was given compared with conventional
      methods. There was one postoperative complication, a mild lymphocele. All
      patients showed normalized serum creatinine levels within 4 d. All grafted
      kidneys showed normal findings on the postoperative ultrasound and renal scans.
      CONCLUSIONS: Minimally invasive video-assisted kidney transplantation is
      technically feasible and may offer benefits in terms of better cosmetic outcomes,
      less pain, and quicker recuperation than conventional kidney transplantation.

PMID- 17561117
TI  - c-Met antisense oligodeoxynucleotides as a novel therapeutic agent for glioma: in
      vitro and in vivo studies of uptake, effects, and toxicity.
AB  - BACKGROUND: c-Met, a receptor tyrosine kinase, and its ligand, hepatocyte growth
      factor, are critical in cellular proliferation, motility, and invasion and are
      known to be overexpressed in gliomas. The aim of our study was to investigate the
      uptake and effects of c-Met antisense oligodeoxynucleotides (ASODNs) on rat and
      human glioma cells in vitro and the uptake and toxicity of these nucleotides in
      rat carcinomatosis and brain tumor models. MATERIALS AND METHODS: The three human
      cell lines (U87, BT325, SHG44) and the C6 rat glioma cell line were cultured. To
      study the uptake of oligodeoxynucleotides (ODNs) by glioma cells in vitro,
      cultured glioma cells readily incorporated caroboxyfluorescein-5-succimidyl ester
      (FAM) labeled phosphorothioate oligodeoxynucleotides, as demonstrated by
      immunofluorescence microscopy and flow cytometry. To study the effect of ASODNs
      treatment on c-Met expression in vitro, Expression of c-Met was assessed by
      immunofluorescence microscopy and reverse transcriptase polymerase chain reaction
      (RT-PCR) analysis. For animal studies of ODNs toxicity and uptake, eight rats
      underwent placement of cisternal catheters, under general anesthesia. Four rats
      were given 24 mug FAM-labeled ASODNs while the others were given a saline control
      injection. After a 24 h observation period, rats were sacrificed by barbiturate
      overdose, and their brains were studied. RESULTS: For all cell lines,
      fluorescence was seen to increase with increasing ASODNs concentration. Cells
      treated in similar fashion were also analyzed by flow cytometry to graphically
      illustrate the differing fluorescence. Multiple glioma cell lines were tested,
      with similar results. c-Met ASODNs was found to be successfully incorporated from
      the media into cultured human glioma cells, even at concentrations as low as 2
      muM. In addition, maintenance of the pH-dependent green fluorescence color, as
      seen by immunofluorescence microscopy and by using flow cytometry, indicated that
      the FAM was not contained within lysosomes. Immunofluorescence microscopy and RT
      PCR analysis showed decreases in c-Met expression with oligodeoxynucleotides
      treatment. Uptake into tumor cells was also demonstrated in vivo, with no
      detectable toxicity at concentrations exceeding expected therapeutic levels.
      CONCLUSION: These data are encouraging for further study of c-Met antisense
      oligodeoxynucleotides as a therapeutic modality for glioma.

PMID- 17561118
TI  - RNA interference targeting hypoxia inducible factor 1alpha reduces post-operative
      adhesions in rats.
AB  - BACKGROUND: To investigate the use of RNA interference mediated gene down
      regulation targeting hypoxia inducible factor 1alpha (HIF-1alpha) and plasminogen
      activator inhibitor 1 (PAI-1) in an effort to prevent abdominal adhesion
      formation. MATERIALS AND METHODS: Real time PCR and a PAI-1 protein activity
      assay were used in vitro to determine the efficacy of small interfering RNAs
      (siRNAs). For in vivo experiments, 57 white female rats were operated to generate
      ischemic and serosal injury to the uterine horns, and treated with saline,
      siRNA(Lamin A/C) (negative control), siRNA(HIF-1alpha), siRNA(PAI-1), or
      siRNA(HIF-1alpha) plus siRNA(PAI-1). The cationic polyer poly(ethylenimine) (PEI)
      was used as the delivery vehicle for all siRNAs delivered in vivo. Adhesions were
      analyzed by a blinded surgeon 8 days post-surgery. RESULTS: After in vitro
      transfection with siRNA, at least 69% gene down-regulation was obtained for all
      siRNAs tested. In vitro siRNA-mediated down-regulation of HIF-1alpha, PAI-1 or
      their simultaneous delivery resulted in a significant decrease of PAI-1 protein
      activity (at least P < 0.05). Administration of 4 nmol siRNA(HIF-1alpha)/PEI
      complexes after injury to the uterine horns achieved a statistical reduction of
      post-operative adhesion formation with a reduction by 52% (P < 0.05). Delivery of
      4 nmol siRNA(PAI-1)/PEI complexes and the simultaneous delivery of 2 nmol
      siRNA(HIF-1alpha) plus 2 nmol siRNA(PAI-1), resulted in a reduction of abdominal
      adhesion by 36% and 42%, respectively, with the reduction being statistically
      significant when compared directly to the saline control (P < 0.01). CONCLUSION:
      These data show that administration of siRNA/PEI complexes within the peritoneal
      cavity can be used to prevent post-operative abdominopelvic adhesions.

PMID- 17561119
TI  - Development of a new flat needle and a reduced surface coating thread for
      endoscopic suturing.
AB  - BACKGROUND: Intracorporeal suturing during endoscopic surgery is a difficult
      procedure. The curved needle is the most difficult to position properly within
      the jaws of the needle driver. The low friction suture materials exhibit good
      knot run-down, but at the expense of increased tendency for slipping. It is
      therefore necessary to invent a new needle and a new thread to facilitate
      intracorporeal suturing. MATERIALS AND METHODS: We made a new flat needle (F
      needle) to facilitate grasping and a new reduced silicone-coated thread to
      prevent the knots from loosening. The time required to grasp the F-needle and the
      round needle (R-needle) by 10 surgeons was measured. The angle between the needle
      and the needle driver was measured. The minimum number of intertwining knots
      required for the knot to hold was counted, and the minimum number of superimposed
      knots that prevented the knots from coming undone when the testing machine
      attempted to release them was counted. RESULTS: The F-needle was grasped in less
      time than the R-needle. The error in yaw angle with the F-needle was smaller than
      in the R-needle. The minimum number of knots needed to hold against the untying
      force with the reduced silicone-coated thread was less than with the conventional
      silicone-coated thread. CONCLUSIONS: The new flat needle was grasped more
      accurately and quickly than the round needles, and the thread with reduced
      surface coating was less likely to loosen. Therefore, the combination of the new
      flat needle and thread with reduced surface coating is useful for endoscopic
      suturing.

PMID- 17561120
TI  - Intranuclear localization and isoform-dependent translocation of 14-3-3 proteins
      in human brain with infarction.
AB  - Immunolocalization of 14-3-3 proteins in human brains with infarction was
      investigated using isoform-specific antibodies. Neurons around acute or subacute
      ischemic foci exhibited an enhanced immunoreactivity for 14-3-3 proteins either
      in the cytoplasm (especially for its sigma isoform) or in the nucleus (especially
      for its beta isoform), and sometimes in both. 14-3-3-like immunoreactivity was
      evaluated in each neuron, which enabled us to identify into three patterns:
      intense cytoplasmic staining with or without nuclear staining; a predominant
      nuclear staining with weak cytoplasmic staining; and an exclusive nuclear
      staining without cytoplamic staining. Quantification of 1500 neurons in relation
      to the severity of ischemia estimated by the relative distance from ischemic foci
      clarified that nuclear immunoreactivity for 14-3-3 proteins was more frequent in
      neurons near the ischemic core. Although the cytoplasm of astrocytes was
      similarly positive for the sigma and the epsilon isoform, their nuclei were only
      immunopositive for the gamma isoform. In the cerebral white matter with ischemia,
      axonal swelling and some nuclei of oligodendrocytes were positive for the zeta
      isoform. Isoform-specific translocation of 14-3-3 proteins into nuclei is a
      cellular reaction to ischemic stress that may be related to survival of neurons
      and their protection against cell death.

PMID- 17561121
TI  - The effects of subthalamic nucleus deep brain stimulation on parkinsonian tremor.
AB  - Deep brain stimulation (DBS) of the ventral intermediate (Vim) nucleus of the
      thalamus has been the target of choice for patients with disabling essential
      tremor or medication refractory parkinsonian tremor. Recently there is evidence
      that the subthalamic nucleus (STN) should be the targets for patients with tremor
      associated with Parkinson's disease (PD). To assess the effects of STN DBS on
      parkinsonian tremor, eight consecutive patients with PD and disabling tremor were
      videotaped using a standardized tremor protocol. Evaluations were performed at
      least 12 h after last dose of medication with the DBS turned off followed by
      optimal DBS on state. A rater blinded to DBS status evaluated randomized video
      segments with the tremor components of the Unified Parkinson Disease Rating Scale
      (UPDRS) and Tremor Rating Scale (TRS). Compared with DBS off state there were
      significant improvements in mean UPDRS tremor score 79.4% (p=0.008), total TRS
      score 69.9% (p=0.008) and upper extremity 92.5% (p=0.008) TRS subscore.
      Functional improvement was noted with pouring liquids. Our findings provide
      support that STN DBS is an effective treatment of tremor associated with PD.

PMID- 17561122
TI  - Memory deficits in amyotrophic lateral sclerosis patients with dementia and
      degeneration of the perforant pathway A clinicopathological study.
AB  - Degeneration of the perforant pathway, not extensively surveyed so far in
      amyotrophic lateral sclerosis (ALS) with dementia, was found in eight out of
      twelve autopsied patients with clinically detectable dementia. Because the
      severity of degeneration of the entorhinal cortex and that of spongiosis of the
      outer half of the molecular layer of the dentate gyrus were correlated in these
      eight patients, it is suspected that the degeneration of the perforant pathway
      may explain these concomitant lesions. This was further corroborated by
      occasional involvement of the parahippocampal white matter and subiculum, other
      components of this pathway. Moreover, six of them manifested clinically
      detectable memory deficits and three of them exhibited amnesia or episodic memory
      impairments similar to Alzheimer's disease (AD). Abnormal intensity restricted
      the dentate gyrus on brain magnetic resonance imaging in a severe case looks like
      the degeneration of the molecular layer. This involvement of the perforant
      pathway in ALS patients and its correlation to memory deficits should be taken in
      account for evaluation of dementia.

PMID- 17561123
TI  - Modelling nematode movement using time-fractional dynamics.
AB  - We use a correlated random walk model in two dimensions to simulate the movement
      of the slug parasitic nematode Phasmarhabditis hermaphrodita in homogeneous
      environments. The model incorporates the observed statistical distributions of
      turning angle and speed derived from time-lapse studies of individual nematode
      trails. We identify strong temporal correlations between the turning angles and
      speed that preclude the case of a simple random walk in which successive steps
      are independent. These correlated random walks are appropriately modelled using
      an anomalous diffusion model, more precisely using a fractional sub-diffusion
      model for which the associated stochastic process is characterised by strong
      memory effects in the probability density function.

PMID- 17561124
TI  - Bacteriophage evolution given spatial constraint.
AB  - Spatial structure can impede mixing, diffusion, and motility. In microbiology
      laboratories, spatial structure is commonly achieved via formation of agar gels,
      within which bacteriophage (phage) replication results in localized clearings
      called plaques. Developing a better understanding of phage plaque formation is
      relevant because of the ubiquity of phage plaquing in the laboratory; because
      plaque size has been employed as a measure of phage fitness; because many
      bacteria exist within environments that display significant spatial structure
      (e.g., biofilms, soils, sediments, and in or on plant or animal tissues); and
      because spatial structure could impede phage exploitation of bacterial
      communities. There is, however, a relative dearth of experimentation and analysis
      considering phage plaque formation from the perspective of selection acting on
      individual phage growth parameters-latent period, burst size, and adsorption
      rate. Here we consider the impact of these parameters on rates of plaque
      wavefront velocity (rates of radial plaque enlargement), especially as functions
      of existing phage and environmental properties. We do so based on analyses of
      published equations which predict plaque enlargement rates. These indicate that
      greater wavefront velocities should be associated with (i) latent period
      reductions, (ii) larger burst sizes, or (iii) faster virion binding to bacteria.
      We suggest, however, that deviations could occur, respectively, (i) if virion
      adsorption is "slow" or if burst sizes are large, (ii) if burst sizes are already
      large, or (iii) if virion binding rates are already fast, bacterial densities are
      especially high, or burst sizes are large. Higher initial lawn bacterial
      densities could also contribute to faster plaque expansion, but only if
      adsorption is otherwise slow or burst sizes are large. By contrast, faster virion
      diffusion is always expected to result in greater plaque wavefront velocities.
      Overall, we provide a snapshot of how phage populations may respond
      evolutionarily to selection for more-rapid propagation during spatially
      constrained growth.

PMID- 17561127
TI  - Effect of intraprostatic local anesthesia during transrectal ultrasound guided
      prostate biopsy: comparison of 3 methods in a randomized, double-blind, placebo
      controlled trial.
AB  - PURPOSE: We evaluated the effect of intracapsular anesthesia and periprostatic
      nerve block during transrectal ultrasound guided prostate biopsy. MATERIALS AND
      METHODS: In a prospective, randomized, double-blind, placebo controlled study 152
      consecutive patients were randomized into 3 groups. Group 1 of 41 patients was
      administered intraprostatic local anesthesia into the right and left sides with a
      total of 2 ml 1% lidocaine and a periprostatic injection of 2 ml saline later.
      Group 2 of 49 patients was administered intraprostatic injection of 2 ml saline,
      followed by periprostatic local anesthesia with 2 ml 1% lidocaine. Group 3 of 62
      patients received intraprostatic and periprostatic local anesthesia with 2 ml 1%
      lidocaine. Patients were asked to grade the pain level using a 10-point linear
      visual analog pain scale 1) when the transrectal ultrasound probe was inserted,
      2) during anesthesia, 3) during biopsy and 4) 20 minutes after biopsy. One-way
      ANOVA and the Kruskal-Wallis test with the Tukey post hoc test were used to
      compare patient characteristics and pain scale responses among the 3 groups.
      RESULTS: No major complications, including sepsis and severe rectal bleeding,
      were noted in any patient. There were statistically significant differences in
      pain scores among groups 1 to 3 during anesthesia (mean +/- SD 5.6 +/- 2.5, 6.7
      +/- 2.3 and 4.9 +/- 2.1, p = 0.003) and during biopsy (4.3 +/- 2.7, 4.5 +/- 2.6
      and 2.7 +/- 2.1, respectively, p = 0.032). There were no differences in pain
      scores among the 3 groups during probe insertion (p = 0.39). CONCLUSIONS: A
      combination of intracapsular anesthesia and periprostatic nerve block is an
      effective and useful technique that is well tolerated by the patient. It
      decreases the level of pain and discomfort associated with the prostatic biopsy
      procedure.

PMID- 17561128
TI  - A new staging system for locally advanced (pT3-4) renal cell carcinoma: a
      multicenter European study including 2,000 patients.
AB  - PURPOSE: We provide an adequate prognostic stratification for locally advanced
      renal cell carcinoma and propose a new TNM classification. MATERIALS AND METHODS:
      We analyzed clinical and pathological data on a large series of patients
      undergoing radical nephrectomy for pT3-4 renal cell carcinoma at 12 European
      centers. Cancer specific survivals were estimated using the Kaplan-Meier method.
      The log rank test was used for comparing survival curves and for univariate
      analysis. The Cox proportional hazards regression model was used for multivariate
      analysis. RESULTS: The analysis included 1,969 patients. Median survivor followup
      was 49 months. Five-year cancer specific survival was 60% for pT3a, 46.2% for
      pT3b, 10% for pT3c and 12% for pT4 tumors (p <0.0001). According to median
      survival we identified 3 prognostic groups, including 1--patients with renal vein
      thrombosis (117 months), fat invasion (98 months) or infradiaphragmatic vena
      caval thrombosis (67 months), 2--patients with adrenal invasion alone (24
      months), renal vein thrombosis plus fat invasion (24 months) or
      infradiaphragmatic vena cava plus fat invasion (24 months) and 3--patients with
      renal or infradiaphragmatic caval thrombosis plus adrenal involvement (11
      months), supradiaphragmatic vena caval thrombosis (12 months) or Gerota's fascia
      invasion (12 months). Five-year cancer specific survival rates in groups 1 to 3
      were 61%, 35% and 12.9%, respectively (p <0.0001). On multivariate analysis the
      proposed classification had an independent prognostic value. CONCLUSIONS: Our
      results suggest the necessity of reclassifying locally advanced renal cell
      carcinoma according to the 3 described prognostic categories.

PMID- 17561129
TI  - The impact factors on prognosis of patients with pT3 upper urinary tract
      transitional cell carcinoma.
AB  - PURPOSE: Stage 3 upper urinary tract transitional cell carcinoma is a
      heterogeneous disease including different tumor locations (pelvis vs ureter) and
      invasion patterns (renal parenchyma, peripelvic fat and periureteral fat).
      Unfortunately the outcomes of patients with pT3 disease with different invasion
      pattern are largely unknown. This study presents the clinical outcome of patients
      with pT3 disease with upper urinary tract transitional cell carcinoma. MATERIALS
      AND METHODS: We retrospectively reviewed the medical records of all patients with
      pT3 disease with upper urinary tract transitional cell carcinoma. Four patient
      groups were classified according to tumor location and tumor invasion pattern.
      Prognostic factors including age, gender, tumor grade, tumor size, tumor number,
      tumor location and microscopic finding of vascular invasion were analyzed with
      respect to disease recurrence and survival. RESULTS: A total of 72 patients were
      included in this study. The most common complaint and tumor relapse pattern were
      painless gross hematuria and distant metastasis, respectively. Patients with pT3
      disease with superficial parenchymal invasion had better disease-free and
      recurrence-free survival than the other 3 groups. Initial tumor location (p =
      0.02) and vascular invasion (p = 0.02) were independent factors for disease-free
      survival, and vascular invasion (p = 0.001) was the only predictive factor for
      recurrence-free survival. CONCLUSIONS: The present study demonstrated that
      patients with pT3 disease with superficial parenchymal invasion should be
      considered to have lower stage disease, and that vascular involvement is the only
      independent prognostic factor for patients with pT3 disease for disease-free and
      recurrence-free survival. Systemic adjuvant therapy should be recommended for
      patients with pT3 disease with vascular involvement.

PMID- 17561131
TI  - Short-term morbidity of primary retroperitoneal lymph node dissection in a
      contemporary group of patients.
AB  - PURPOSE: We defined the blood loss, operative time and short-term morbidity of
      primary retroperitoneal lymph node dissection in a contemporary series to assess
      whether laparoscopic retroperitoneal lymph node dissection actually confers the
      magnitude of benefit claimed. MATERIALS AND METHODS: A retrospective chart review
      was performed of 75 consecutive patients who underwent primary retroperitoneal
      lymph node dissection during the 18 months ending May 2005. Two patients were
      excluded, including 1 who underwent right hemicolectomy for cecal adenocarcinoma
      and 1 with a pure seminomatous intra-abdominal testicle. RESULTS: Of the 73
      patients 69 (94%) underwent unilateral dissection and 60 (82.2%) underwent a
      nerve sparing procedure. Mean operative time was 132 minutes (range 81 to 246)
      and mean blood loss was 207 cc (range 50 to 500). Nasogastric tubes were placed
      in 2 patients (2.7%). Mean time to start clear liquids was 1.0 day. Mean hospital
      stay was 2.8 days (range 2 to 4). CONCLUSIONS: The short-term morbidity of open
      retroperitoneal lymph node dissection, including operative time, blood loss and
      hospital stay, has significantly improved compared to historical controls.
      Perioperative management has changed with time. Comparing the morbidity of
      laparoscopic retroperitoneal lymph node dissection to that of historical controls
      is inappropriate.

PMID- 17561132
TI  - Is the GPSM scoring algorithm for patients with prostate cancer valid in the
      contemporary era?
AB  - PURPOSE: The GPSM (Gleason, prostate specific antigen, seminal vesicle and margin
      status) scoring algorithm is a user friendly model for predicting biochemical
      recurrence following radical retropubic prostatectomy. It was developed from
      patients who underwent radical retropubic prostatectomy from 1990 to 1993. We
      investigated the predictive ability of GPSM in the contemporary era. MATERIALS
      AND METHODS: We identified 2,728 patients who underwent radical retropubic
      prostatectomy for prostate cancer from 1997 to 2000 at our institution. Cox
      proportional hazard regression models were used to develop multivariate scoring
      algorithms. Harrell's measure of concordance was used to compare the competing
      models. RESULTS: In the contemporary era each GPSM feature remained significantly
      associated with biochemical recurrence in a multivariate model (each p <0.001).
      Harrell's measure of concordance for the algorithm was 0.706 vs 0.718 in the
      original study. After adjusting for GPSM on multivariate analysis Gleason primary
      4/5 (p <0.001), DNA ploidy (p = 0.018) and tumor size (p <0.001) were associated
      with biochemical recurrence. However, none of these features increased Harrell's
      measure of concordance greater than 0.01 when added to the GPSM model. In
      addition, using the original 1990 to 1993 cohort, 495 patients with a GPSM score
      of 10 or greater were significantly more likely to die of prostate cancer
      compared with 2,169 with a GPSM score of less than 10 (at 15 years 13% vs 2%, HR
      6.5, p <0.001). CONCLUSIONS: The GPSM scoring algorithm is a simple predictive
      model that remains associated with biochemical recurrence in the contemporary
      era. In addition, to our knowledge the GPSM algorithm is the first nomogram
      associated with survival in patients with prostate cancer.

PMID- 17561133
TI  - Impact of nerve sparing technique on patient self-assessed outcomes after radical
      perineal prostatectomy.
AB  - PURPOSE: We investigated the impact of nerve sparing technique on erectile
      function, urinary continence and health related quality of life after radical
      perineal prostatectomy using a validated self-assessment questionnaire. MATERIALS
      AND METHODS: The Expanded Prostate Cancer Index Composite questionnaire was
      administered preoperatively and at defined intervals after surgery to 265
      patients who underwent radical perineal prostatectomy at 2 institutions between
      January 2001 and December 2004. Of these patients 153 (57.7%) and 112 (42.3%)
      underwent nonnerve sparing and nerve sparing approaches, respectively. Kaplan
      Meier analysis was used to determine time to recovery of erectile function
      (erections firm enough for intercourse) and urinary continence (0 pads per day).
      RESULTS: Median patient age was 60.6 years. Median followup was 15 months. In
      multivariate analysis preoperative erectile function (p = 0.005) and preservation
      of the neurovascular bundle (p = 0.018) were independent predictors of earlier
      recovery of erectile function, with hazard ratios of 2.3 (95% CI 1.2-4.6) and 4.0
      (95% CI 1.5-10.3), respectively. Median time to recovery of urinary continence
      was 4.8 months in the nerve sparing group and 6.1 months in the nonnerve sparing
      group (p = 0.001). In multivariate analysis nerve sparing technique (p = 0.001,
      HR 1.4, 95% CI 1.1-1.9) and age (p = 0.012, HR 1.7, 95% CI 1.3-2.2) were
      independent predictors of recovery of continence. CONCLUSIONS: This analysis
      suggests that nerve sparing radical perineal prostatectomy is associated with
      improved recovery of urinary continence and favorable health related quality of
      life scores and, therefore, should be considered a viable alternative to other
      nerve sparing approaches.

PMID- 17561135
TI  - Low incidence of perioperative chemotherapy for stage III bladder cancer 1998 to
      2003: a report from the National Cancer Data Base.
AB  - PURPOSE: Studies of perioperative chemotherapy for muscle invasive bladder cancer
      have shown a survival benefit with combined modality therapy. We reviewed
      chemotherapy use in patients with stage III transitional cell carcinoma of the
      bladder from 1998 to 2003 to evaluate perioperative chemotherapy treatment
      patterns. MATERIALS AND METHODS: The National Cancer Data Base collected data on
      approximately 60% of all newly diagnosed bladder cancer cases in the United
      States from 1998 to 2003. We queried the National Cancer Data Base for all
      treatment of male and female patients 18 years old or older with bladder
      transitional cell carcinoma diagnosed between 1998 and 2003. A total of 224,060
      bladder transitional cell carcinoma records were reviewed. Perioperative
      chemotherapy was defined as chemotherapy given within 4 months before and 4
      months after surgery. Of 11,339 cases of stage III bladder cancer treatment,
      analysis was possible for 7,161. RESULTS: Treatment patterns were analyzed in
      7,161 patients with stage III bladder transitional cell carcinoma. Perioperative
      chemotherapy was administered to 11.6% of patients with stage III bladder
      transitional cell carcinoma with 10.4% receiving adjuvant chemotherapy and 1.2%
      receiving neoadjuvant chemotherapy. When comparing perioperative chemotherapy use
      by diagnosis year in 1998 and 2003, a small statistically significant increase
      was observed using the Pearson's chi-square test with Bonferroni correction (p
      <0.05) at 11.3% of patients in 1998 vs 16.8% in 2003. CONCLUSIONS: Perioperative
      chemotherapy is underused in the management of surgically resectable stage III
      transitional cell carcinoma of the bladder. This finding may reflect a delay in
      implementing the results of recently reported randomized trials, a low incidence
      of referrals by urologists for chemotherapy and/or confidence in salvage
      chemotherapy as an equivalent alternative. Further followup will determine if
      this treatment pattern changes in the future.

PMID- 17561137
TI  - Comparison of contrast enhanced color Doppler targeted biopsy to conventional
      systematic biopsy: impact on Gleason score.
AB  - PURPOSE: Prostate cancer grading with Gleason score is an important prognostic
      factor. This prospective randomized study compares ultrasound systematic biopsy
      vs contrast enhanced color Doppler targeted biopsy for the impact on Gleason
      score findings. MATERIALS AND METHODS: We examined 690 men (mean age 56 years,
      range 41 to 77) with a serum total prostate specific antigen of 1.25 ng/ml or
      greater, a free-to-total prostate specific antigen ratio less than 18% and/or a
      suspicious digital rectal examination. Contrast enhanced color Doppler targeted
      biopsies with a limited number of cores (5 or less) were performed in
      hypervascular areas of the peripheral zone during administration of the
      ultrasound contrast agent Sonovuetrade mark (Bracco, Milano, Italy). Ten
      systematic biopsies were obtained in a standard spatial distribution. Cancer
      detection rates and Gleason score were compared. RESULTS: Prostate cancer was
      identified in 221 of 690 subjects (32%) with a mean prostate specific antigen of
      4.6 ng/ml (range 1.4 to 35.0). Prostate cancer was detected in 180 of 690
      subjects (26%) with contrast enhanced color Doppler targeted biopsy and in 166 of
      690 patients (24%) with systematic ultrasound biopsy. The Gleason score of all
      180 cancers detected on contrast enhanced color Doppler targeted biopsy was 6 or
      higher (mean 6.8). The Gleason score of all 166 cancers detected on systematic
      biopsy ranged from 4 to 6 and mean Gleason score was 5.4. Contrast enhanced color
      Doppler targeted biopsy detected significantly higher Gleason scores compared to
      systematic biopsy (Wilcoxon rank sum test p <0.003). CONCLUSIONS: Contrast
      enhanced color Doppler targeted biopsy detected cancers with higher Gleason
      scores and more cancer than systematic biopsy. Therefore, contrast enhanced color
      Doppler seems to be helpful in the grading of prostate cancer, which is important
      for defining prognosis and deciding treatment.

PMID- 17561140
TI  - The guestbook of the urology department of Semmelweis University in Budapest: a
      mirror of international contacts.
AB  - PURPOSE: The Department of Urology at Semmelweis University, Budapest was
      established in 1920 as one of the first independent urological clinics in Europe.
      The history of the guestbook begins in 1922 with Professor Illyes, the first
      appointed head of the department. MATERIALS AND METHODS: Information was
      collected on the most famous urologists from those times, who were mostly working
      in the United States. In addition, guests from around the world were grouped
      according to the countries from which they came, highlighting the political
      situation of those times in Hungary. RESULTS: Before World War II guests mostly
      came from the United States and a few other countries. However, after World War
      II almost no Western European or American guests visited, but there were still
      many urologist visitors from the Soviet Union and Eastern block countries. With a
      slight political improvement in 1961 Western European and American urologists
      increased visits to the department. Since 1997 Professor Imre Romics has been the
      department chair, and has seen the greatest number of visitors from around the
      world. CONCLUSIONS: The guestbook of the Semmelweis University Department of
      Urology is a real mirror of international contacts, and represents the last few
      decades of history of a country in the heart of middle Europe.

PMID- 17561141
TI  - A preoperative prognostic nomogram for solid enhancing renal tumors 7 cm or less
      amenable to partial nephrectomy.
AB  - PURPOSE: Small renal masses are increasing in incidence. Most tumors 7 cm or less
      are treated with radical or partial nephrectomy but clinicians are increasingly
      relying on ablative therapies and observation for some small renal masses. We
      present novel nomograms that predict the likelihood of benign, likely indolent or
      potentially aggressive pathological findings based only on readily identifiable
      preoperative factors. MATERIALS AND METHODS: Information on all partial
      nephrectomies performed at a single institution was collected in an institutional
      review board approved registry. Using retrospectively collected data on all 862
      patients who underwent partial nephrectomy for a single, solid, enhancing,
      clinical T1 (7 cm or less) tumor between 1999 and 2005 tumors were classified as
      benign or malignant. Grade 3 clear cell renal cell carcinoma, grade 4 renal cell
      carcinoma of any type and any renal cell carcinoma with vascular, fat or
      collecting system invasion were considered potentially aggressive. The likelihood
      of benign, likely indolent or potentially aggressive pathological findings was
      modeled using multivariable logistic regression models based on age, gender,
      radiographic tumor size, symptoms at presentation and smoking history. RESULTS:
      Of 862 small renal masses 20% were benign and 80% were malignant but only 30% of
      cancers (24% of small renal masses) were potentially aggressive. All 11 patients
      with systemic symptoms had cancer. The remaining 851 patients underwent further
      analysis. Factors that were most strongly associated with the likelihood of
      benign pathology were age, gender, tumor size and smoking history. A nomogram
      constructed to predict benign histology proved to be relatively accurate and
      discriminating (bootstrap corrected concordance index 0.644) and calibrated.
      Small renal masses in older men and younger women were more likely to be benign.
      With regard to differentiating indolent from potentially aggressive cancers, only
      advanced age was independently significant on multivariate analysis (p <0.005).
      The nomogram for this outcome performed with limited ability (concordance index
      0.557). CONCLUSIONS: Clinical factors provide substantial predictive ability to
      predict benign vs malignant pathology for small renal masses amenable to partial
      nephrectomy. Although most of these small renal masses are benign or indolent,
      our ability to predict potentially aggressive cancer in this population remains
      limited.

PMID- 17561142
TI  - Radical prostatectomy: a current perspective.

PMID- 17561143
TI  - Modifiable risk factors for benign prostatic hyperplasia and lower urinary tract
      symptoms: new approaches to old problems.
AB  - PURPOSE: Benign prostatic hyperplasia is generally not regarded as a preventable
      disease. However, accumulating evidence suggests that modifiable factors may
      influence the risk of benign prostatic hyperplasia and lower urinary tract
      symptoms. MATERIALS AND METHODS: A structured, comprehensive literature review
      was done to identify modifiable risk factors for benign prostatic hyperplasia and
      lower urinary tract symptoms among observational studies of older men. RESULTS:
      Outcome measures used to define benign prostatic hyperplasia in clinical studies
      include histological analysis of prostate tissue, radiographically determined
      prostate enlargement, acute urinary retention, decreased urinary flow rate,
      pressure flow studies consistent with bladder outlet obstruction, history of
      benign prostatic hyperplasia surgery, physician diagnosed benign prostatic
      hyperplasia and American Urological Association symptom score or International
      Prostate Symptom Score. Factors that potentially increase the risk of benign
      prostatic hyperplasia and lower urinary tract symptoms include obesity and
      diabetes. Factors that potentially decrease the risk include increased physical
      activity and moderate alcohol consumption. Other candidate factors for which
      clear risk patterns have not yet emerged are dyslipidemia, hypertension, smoking,
      diet and environment. CONCLUSIONS: Obesity, diabetes, physical activity and
      alcohol intake may substantially influence the risk of benign prostatic
      hyperplasia and lower urinary tract symptoms in older men. Further analyses of
      these and other potential modifiable risk factors may identify novel
      interventions for the prevention, diagnosis and treatment of these highly
      prevalent conditions.

PMID- 17561145
TI  - Laparoscopic partial nephrectomy: single center experience with 140 patients-
      evolution of the surgical technique and its impact on patient outcomes.
AB  - PURPOSE: We analyzed the outcome of laparoscopic partial nephrectomy in 140
      patients and defined the evolution of the operative technique and its impact on
      patient outcomes. MATERIALS AND METHODS: Preoperative tumor characteristics,
      intraoperative parameters (blood loss, ischemia time, complication and conversion
      rates) and postoperative parameters (complications, surgical margins status and
      followup) were compared between the initial 30 patients (group 1) and the last
      110 (group 2). Statistical analysis was done using the Student t test with p
      <0.05 considered significant. The impact of modifications in the surgical
      technique on the outcome of surgery is discussed. RESULTS: Group 1 consisted of
      exophytic, peripherally located tumors, whereas in group 2 central and hilar
      tumors were also included. The 2 groups were also different regarding mean tumor
      size (2.6 vs 3.9 cm p <0.05), conversion rates (10% vs 2.7%, p <0.05),
      postoperative complication rates (urine leakage 10% vs 1.4% and reoperation 6% vs
      1.8%, p <0.05) and positive margins (10% vs 3.6%, p <0.05). Mean warm ischemia
      time (32 vs 29 minutes) and blood loss (460 vs 510 ml) were similar (each p
      >0.05). Renal cell carcinoma was found in 78% and 86% of cases, respectively.
      Overall 7 cases (5%) had focally positive surgical margins, including 3 in group
      1 and 4 in group 2. At followup no tumor recurrences were observed. CONCLUSIONS:
      Laparoscopic partial nephrectomy is a challenging procedure with potentially
      major complications. However, accumulated experience and adherence to a
      standardized surgical technique translate into improved outcomes.

PMID- 17561148
TI  - Assessing retroperitoneal lymphadenectomy experience in United States urological
      residency programs.
AB  - PURPOSE: Surgical experience is important for the mastery of operative
      procedures. We evaluated the current United States urological surgical resident
      training in performing retroperitoneal lymph node dissection. MATERIALS AND
      METHODS: The Accreditation Council for Graduate Medical Education Residency
      Review Committee for Urology operative log reports from 2000 through 2004 were
      reviewed. We analyzed resident retroperitoneal lymph node dissection experience
      as surgeon and first assistant by examining CPT codes for retroperitoneal lymph
      node dissection (CPT codes 38780, 38570 and 38572). RESULTS: The overall number
      of retroperitoneal lymph node dissections performed at urological residency
      training programs has increased from 2000 to 2004 (781 to 924). The average
      number of retroperitoneal lymph node dissections performed by graduating
      residents in 2001 and 2004 did not change significantly (3.5 vs 4.0). Half of all
      graduating urology residents in 2004 had performed 2 or fewer retroperitoneal
      lymph node dissections as the primary surgeon and 1 or none as the first
      assistant during their training program. However, a small percentage (10%) of
      graduating residents completed their respective programs with 9 or more
      retroperitoneal lymph node dissections as primary surgeon and 4 as first
      assistant. There were no laparoscopic retroperitoneal lymph node dissections
      logged by graduating residents from 2001 through 2004. CONCLUSIONS: Accreditation
      Council for Graduate Medical Education data suggest that many urology residents
      have minimal surgical exposure and training in retroperitoneal lymphadenectomy.
      These results indicate that alternative strategies should be explored not only to
      improve the residency training experience but also to determine minimum training
      criteria.

PMID- 17561150
TI  - The oral mucosa graft: a systematic review.
AB  - PURPOSE: We provide the reader with a critical, nonbiased, systematic review of
      current and precedent literature regarding the use of oral mucosa in the
      reconstruction of urethral defects associated with stricture and
      hypospadias/epispadias. MATERIALS AND METHODS: We reviewed pertinent English
      literature from January 1966 through August 1, 2006 via the databases
      MEDLINE/PubMed, the Cochrane Library, and EMBASE Drugs and Pharmacology regarding
      the use of oral mucosa graft urethroplasty in the reconstruction of urethral
      defects associated with stricture and hypospadias/epispadias. Bibliographies of
      pertinent articles were explored for additional important literature. RESULTS:
      Data were stratified among studies that only used oral mucosa graft urethroplasty
      in the reconstruction of urethral defects associated with stricture, and those
      that used oral mucosa graft urethroplasty in the reconstruction of urethral
      defects associated with hypospadias/epispadias. Recipient site success in the
      reconstruction of defects associated with stricture was significantly associated
      with the location of graft placement (ventral vs dorsal, p <0.001) when an onlay
      graft was used. Hypospadias/epispadias recipient site success was significantly
      associated with the type of graft used (tube vs onlay, p <0.001), and by the site
      of oral mucosa harvest (labial vs buccal, p <0.001). Other perioperative and
      patient oriented variables were not significantly associated with success at the
      recipient site. CONCLUSIONS: The oral mucosa is a viable source of donor tissue
      displaying many characteristics of the ideal urethral graft. There are numerous
      variations of the oral mucosa graft urethroplasty technique. Herein comparisons
      are made.

PMID- 17561151
TI  - Results of inferior vena caval interruption by greenfield filter, ligation or
      resection during radical nephrectomy and tumor thrombectomy.
AB  - PURPOSE: Surgical resection for patients with renal cell carcinoma and venous
      tumor thrombus may require interruption of the inferior vena cava using a
      Greenfield filter, ligation or resection. We describe the indications, technique,
      complications and outcomes of vena caval interruption during nephrectomy with
      tumor thrombectomy. MATERIALS AND METHODS: We identified 160 patients treated for
      level II-IV tumor thrombus at our institution between 1970 and 2004. Operative
      reports were reviewed to establish vena caval interruption. All patients who
      underwent interruption were assessed for postoperative disability according to
      the American Venous Forum International Consensus Committee. RESULTS: Vena caval
      interruption was performed in 40 of 160 cases (25%), including 14 level II, 10
      level III and 16 level IV thrombi. A total of 34 patients (85%) were symptomatic
      at presentation. A Greenfield filter was deployed before cavotomy closure in 4 of
      160 patients (2.5%) for bland thrombus of the infrarenal vena cava. Vena caval
      ligation was used for bland thrombus that completely occluded the infrarenal vena
      cava in 23 of 160 patients (14.4%), while segmental vena caval resection was
      performed for tumor thrombus growing into the wall of the vena cava or for tumor
      thrombus that interfaced with bland thrombus in 13 of 160 (8.1%). Postoperatively
      no case was class 3 disability, 12 of 40 (30%) were class 2, 12 of 40 (30%) were
      class 1 and 16 of 40 (40%) showed no disability. CONCLUSIONS: The need to
      interrupt the inferior vena cava is not infrequent in patients undergoing radical
      nephrectomy and tumor thrombectomy, and it may be well tolerated postoperatively.
      Management should be based on the degree of venous occlusion and the presence of
      bland thrombus.

PMID- 17561152
TI  - Radical prostatectomy for clinically localized, high risk prostate cancer:
      critical analysis of risk assessment methods.
AB  - PURPOSE: Standardized criteria are lacking to define high risk, clinically
      localized prostate cancer before definitive treatment. Reliance on simple risk
      stratification schemes to define high risk cancers has led many physicians and
      patients toward therapeutic nihilism, inappropriately selecting androgen
      deprivation instead of definitive local therapy. Of patients undergoing radical
      prostatectomy we identified those at high risk based on 8 previously described
      definitions. We examined pathological characteristics and prostate specific
      antigen outcomes. MATERIALS AND METHODS: The study population included 4,708 men
      treated with radical prostatectomy alone between 1985 and 2004. Estimates of
      prostate specific antigen relapse for patients at high risk were generated with
      the Kaplan-Meier method. Cox proportional hazards regression was used to estimate
      the HR for recurrence in high risk vs nonhigh risk cohorts. RESULTS: Depending on
      the definition used patients at high risk composed 3% to 38% of the study
      population. The proportion of patients with extracapsular extension, seminal
      vesicle invasion and lymph node metastasis among men with high risk cancer was
      35% to 71%, 10% to 33% and 7% to 23%, respectively. Of the high risk tumors 22%
      to 63% proved to be confined to the prostate pathologically. While patients at
      high risk had a 1.8 to 4.8-fold increased hazard of prostate specific antigen
      relapse, their 5-year relapse-free probability after radical prostatectomy alone
      was 49% (95% CI 39 to 58) to 80% (95% CI 77 to 83). Of patients at high risk who
      had relapse 25% across all definitions experienced relapse more than 2 years
      after surgery and in 26% to 39% prostate specific antigen doubling time at
      recurrence was 10 months or greater. CONCLUSIONS: Patients diagnosed with high
      risk cancer by currently available definitions do not have a uniformly poor
      prognosis after radical prostatectomy. Many cancers classified clinically as high
      risk are actually confined to the prostate pathologically. The risk of
      extraprostatic disease and prostate specific antigen relapse varies greatly
      depending on the definition used.

PMID- 17561156
TI  - Conservative surgical therapy for leydig cell tumor.
AB  - PURPOSE: We performed a long-term evaluation of conservative surgical treatment
      of benign Leydig cell tumor. MATERIALS AND METHODS: A multicenter retrospective
      clinical study was performed at 6 European centers. Case files of all patients
      diagnosed with Leydig cell tumor and treated with conservative surgery were
      examined. Patients underwent physical examination, hormone and tumor marker
      assays, scrotal and abdominal ultrasound, chest x-ray, and an endocrinological
      examination. RESULTS: From 1987 to 2006, 22 patients with Leydig cell tumor
      underwent conservative surgery. Mean patient age was 35 years (range 5 to 61).
      Mean followup was 47 months (range 1 to 230). No local recurrence or metastasis
      was observed. Patients presented with a palpable testicular nodule (3 patients,
      13.7%) or a nodule diagnosed by ultrasound (15 patients, 68.2%), gynecomastia (2
      patients, 9.1%), precocious pseudopuberty (1 patient, 4.5%) or scrotal pain (1
      patient, 4.5%). Three patients were monorchid after contralateral orchiectomy for
      inguinal hernia repair (1 patient, 28 years before surgery) and nonseminomatous
      germ cell tumor (2 patients, 1 month and 6 years before surgery). Diagnosis after
      frozen section examination was Leydig cell tumor in 20 of 22 cases (91.0%). Mean
      histological size of the nodule was 1.11 cm (range 0.5 to 2.5). Preoperative FSH
      and LH levels were high in 4 patients. Tumor markers were normal before and after
      surgery. Followup was conducted for all patients every 3 to 6 months with
      physical examination, tumor markers, scrotal and abdominal ultrasound, chest x
      ray. Six patients (27.3%) underwent abdominal computerized tomography.
      CONCLUSIONS: When diagnosed early Leydig cell tumors present a favorable
      followup. In select cases with motivated patients, conservative surgery proved to
      be a feasible and safe choice.

PMID- 17561159
TI  - Pay for performance: rationale and potential implications for urology.
AB  - PURPOSE: Pay for performance represents a new paradigm for physician
      reimbursement based on the value based purchasing of health care services.
      Government and private payers have expressed an interest in moving toward this
      system with several pay for performance programs already in place. The rationale
      behind this initiative and what it means for the practicing urologist are
      discussed. MATERIALS AND METHODS: MEDLINE and Internet based research focusing on
      the topics of health care quality, measures used to implement pay for
      performance, and private and public sector experience with pay for performance to
      date were reviewed. RESULTS: Health care quality can be assessed through 3 types
      of measures, including structure, process and outcome. Structure measures involve
      the environment where services are provided, whereas process measures capture how
      a particular provider delivers health care. Outcome assessment involves the
      results of the services provided. These measures are best used when they are used
      in coordination with each other, and when they are risk adjusted. Most pay for
      performance systems in use today are based on these measures. However, there are
      little data that show whether this reimbursement paradigm actually improves the
      quality of heath care provided. CONCLUSIONS: Many questions remain regarding the
      implementation of a pay for performance system in the field of urology.
      Government and private payers are motivated to implement pay for performance.
      However, specific evidence based metrics for urology that fairly and accurately
      define quality are currently lacking. Given that implementation of a nationwide
      pay for performance system appears to be inevitable, urology involvement in the
      development and implementation of these health care quality metrics is essential.

PMID- 17561160
TI  - A direct comparison of robotic assisted versus pure laparoscopic radical
      prostatectomy: a single institution experience.
AB  - PURPOSE: We compared a single institution experience with radical prostatectomy
      using a pure laparoscopic technique vs a robotically assisted technique with
      regard to preoperative, intraoperative or postoperative parameters. MATERIALS AND
      METHODS: From May 2003 to May 2005 we reviewed 133 consecutive patients who
      underwent extraperitoneal robot assisted radical prostatectomy and compared them
      to 133 match-paired patients treated with a pure extraperitoneal laparoscopic
      approach. The patients were matched for age, body mass index, previous
      abdominopelvic surgery, American Society of Anesthesiologists score, prostate
      specific antigen, pathological stage and Gleason score. Preoperative,
      perioperative and postoperative data, including complications and oncological
      results, were analyzed between the 2 groups. RESULTS: The 2 groups were
      statistically similar with respect to age, body mass index, prostate specific
      antigen, Gleason score and clinical stage. No statistical differences were
      observed regarding operative time, estimated blood loss, hospital stay or bladder
      catheterization between the 2 groups. The transfusion rate was 3% and 9.8% for
      laparoscopic radical prostatectomy and robotic assisted laparoscopic
      prostatectomy, respectively (p = 0.03). Conversion from robotic assisted
      laparoscopic prostatectomy to laparoscopic radical prostatectomy was necessary in
      4 cases. None of the laparoscopic radical prostatectomy cases required conversion
      to an open technique. The percentage of major complications was 6.0% vs 6.8%,
      respectively (p = 0.80). The overall positive margin rate was 15.8% vs 19.5% for
      laparoscopic radical prostatectomy and robotic assisted laparoscopic
      prostatectomy, respectively (p = 0.43). CONCLUSIONS: We demonstrated that the
      laparoscopic extraperitoneal radical prostatectomy is equivalent to the robotic
      assisted laparoscopic prostatectomy in the hands of skilled laparoscopic
      urological surgeons at our institution with respect to operative time, operative
      blood loss, hospital stay, length of bladder catheterization and positive margin
      rate.

PMID- 17561161
TI  - Small renal tumors: correlation of clinical and pathological features with tumor
      size.
AB  - PURPOSE: We analyzed the association between tumor diameter and pathological
      stage, histological subtype, tumor grade and the incidence of metastases in renal
      cell carcinoma with a diameter of up to 4 cm (clinical stage T1a). MATERIALS AND
      METHODS: We analyzed a consecutive series of 663 patients with renal tumors 4 cm
      or less who underwent surgery at our institution between 1990 and 2006. After
      excluding 115 patients (17.3%) with benign tumors 548 with renal cell carcinoma
      were included in the study. Tumor size on preoperative imaging was correlated
      with pathological stage, tumor grade, histological subtype and incidence of
      metastases at diagnosis. For data analysis tumors were stratified by tumor
      diameter into 3 groups, including 2 cm--99 patients with tumors up to 2 cm, 3 cm-
      234 with tumors between 2.1 and 3.0 cm, and 4 cm--215 with tumors between 3.1 and
      4.0 cm in diameter. RESULTS: Median clinical diameter of renal cell carcinoma in
      the whole series was 2.93 cm (range 0.8 to 4.0). Tumor stage was pT1a, pT1b and
      pT3 in 84.5%, 8.0% and 7.5% of cases, respectively. Tumor grade was 1 to 3 in
      24.5%, 65.0% and 10.6% of cases, respectively. The renal cell carcinoma
      histological subtype was clear cell carcinoma in 77.9% of patients, papillary
      carcinoma in 15.3% and chromophobe carcinoma in 6.8%. Advanced tumor stage (pT3)
      was found in 3.0%, 5.1% and 12.1% of the patients in the 2, 3 and 4 cm groups,
      respectively (p <0.05). Grade 3 was found in 7.1%, 9.0% and 14.0% of the patients
      in the 2, 3 and 4 cm groups, respectively (p <0.05). Metastases at diagnosis were
      found in 3.0%, 2.6% and 6.0% of the patients in the 2, 3 and 4 cm groups,
      respectively. CONCLUSIONS: Negative prognostic features increase with tumor
      diameter and they are associated with even small tumors. However, above a tumor
      size of 3.0 cm there is a sharp increase in the incidence of negative prognostic
      parameters. New diagnostic tests are warranted to better stratify patients with
      respect to treatment aggressiveness for small incidental renal tumors.